PMID- 10940879
TI  - Gamma-glutamyltranspeptidase knockout mice as a model for understanding the
      consequences of diminished glutathione on T cell-dependent immune responses.
AB  - Gamma-Glutamyltranspeptidase (GGT) catalyzes the first step in the extracellular
      hydrolysis of glutathione (GSH) and plays a critical role in GSH recycling;
      however, little is known about the impact of diminished GGT activity on immune
      function. We report here that GGT knockout (GGT(-/-)) mice have a 30 % decrease
      in splenic GSH and a 50 % reduction in thymus and spleen cellularity. The
      decreased cellularity was not selective for one population of cells, as each
      population was equivalently reduced. Following antigen challenge, GSH levels were
      reduced by 20-40 % in CD4+ and CD8+ T cells from GGT(-/-) mice when compared to T
      cells from wild-type mice. To test whether decreased GSH impairs immunity, we
      examined immune responsiveness following in vivo challenge with four different T
      cell-dependent stimuli. While there was no alteration in the antibody response to
      ovalbumin and sheep erythrocytes, cytotoxic T lymphocyte and alloantibody
      activity against P815 cells were decreased by 30 % and 65 %, respectively.
      Compared to wild-type littermates, anti-CD3-induced IL-2 and IL-6 production were
      also diminished in GGT(-/-) mice. These results demonstrate differential effects
      of decreased GSH on in vivo immune responsiveness to distinct stimuli, and
      suggest an important immunoregulatory role for GSH.

PMID- 10940880
TI  - Chemokine expression by central nervous system resident cells and infiltrating
      neutrophils during experimental autoimmune encephalomyelitis in the BALB/c mouse.
AB  - The active role of chemokines in the central nervous system (CNS) during the
      pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly
      established. In this study the expression pattern of several chemokines and
      cytokines was elucidated using reverse transcription-PCR and immunohistochemistry
      in a recently established EAE model of the BALB/c mouse that is characterized by
      CNS infiltration of polymorphonuclear neutrophils. Elevated mRNA levels of the
      chemokines MIP-1alpha, MIP-2 and MCP-1 were detected in the CNS of diseased mice,
      whereas no chemokine expression could be measured in asymptomatic mice. Activated
      astrocytes were shown to be the main source of MIP-1alpha and MIP-2 before and
      during cellular CNS infiltration. Among the infiltrating immune cells the
      neutrophils secreted MIP-1alpha and MCP-1. These results suggest involvement of
      ordered chemokine expression during the process of neutrophil attraction into the
      CNS, which may play an important role in the initiation and perpetuation of
      autoimmune CNS inflammation in the BALB/c mouse. This is the first EAE model to
      describe CNS expression of the C-X-C chemokine MIP-2, corresponding to an
      observed neutrophil accumulation in the CNS.

PMID- 10940881
TI  - Activation of hepatic NKT cells and subsequent liver injury following
      administration of alpha-galactosylceramide.
AB  - It has been established that alpha-galactosylceramide (alpha-GalCer), a
      glycolipid, is recognized by natural killer T (NKT) cells together with the
      monomorphic MHC-like antigen, CD1d, in mice and humans. In this study, we
      examined how NKT cells are modulated by in vivo administration of alpha-GalCer in
      mice. When 2 microg (or more)/mouse of alpha(-GalCer was injected i.p., the
      majority of NKT cells disappeared in the liver and spleen, possibly undergoing
      apoptosis, on day 1. At this time, NKT cytotoxicity seen in liver lymphocytes
      also disappeared. In parallel with this numerical and functional change of NKT
      cells, there was always concomitant hepatocyte damage, as shown by histology and
      elevated levels of transaminases. Subsequently, the number and function of NKT
      cells continued to increase from day 3 to day 7. The response seen in hepatic
      (and splenic) NKT cells did not occur in thymic NKT cells. All these phenomena
      induced in the liver did not appear in NKT-deficient mice such as beta2
      microglobulin(-/-) and CD1d(-/-) mice. These results shed further light on the in
      vivo interaction between NKT cells and alpha-GalCer in mice.

PMID- 10940882
TI  - T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type
      immune response following infection with Nippostrongylus brasiliensis.
AB  - The IL-1 receptor-related protein T1 is expressed on the surface of Th2, but not
      Th1 cells. Studies with anti-T1 monoclonal antibodies have suggested that T1 is
      critical for development of normal Th2-type responses. To elucidate the role of
      T1 in vivo, we generated T1-deficient mice and a T1-transgenic strain which
      secretes soluble T1-Fc fusion protein into the serum. These were analyzed for the
      Th2 immune response induced by infection with the parasitic nematode
      Nippostrongylus brasiliensis. Although Th2 cytokine production by lymph node
      cells was similar in all groups of N. brasiliensis-infected mice, a decrease in
      IL-5 production by lung lymphocytes was detected in both T1-deficient and T1-Fc
      transgenic mice compared to control littermates. This difference in IL-5
      production did not influence blood eosinophilia, but recruitment of eosinophils
      into lung tissue, especially in T1-Fc-transgenic mice was slightly decreased.
      However, induction of all other immune parameters was normal and both T1
      deficient and T1-Fc-transgenic mice were able to clear the parasite infection
      within 12 days with kinetics similar to those in control mice. Therefore, in
      contrast to previous suggestions, we conclude that the T1 protein is not
      obligatory for normal development of Th2 immune responses.

PMID- 10940883
TI  - Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting
      and potent induction of cell-mediated and humoral immunity.
AB  - Immunostimulatory DNA sequences (ISS) are a potent Th1 adjuvant. We hypothesized
      that conjugation of ISS to protein antigens would strongly enhance their
      immunogenicity because both antigen and adjuvant (ISS) would be delivered to the
      same locale/antigen-presenting cell. To test this hypothesis, we conjugated a 22
      mer immunostimulatory oligodeoxynucleotide (ISS-ODN) to two test antigens of
      differing intrinsic immunogenicity, namely Escherichia coli beta-galactosidase
      and the HIV-1 envelope glycoprotein gp120. We show that the antigen-ISS
      conjugates rapidly induce Th1 cells secreting high levels of IFN-gamma, strong
      CTL activity, and high titer IgG2a and HIV-neutralizing antibodies, exceeding
      gene and protein vaccination alone or immunization with mixtures of antigen and
      ISS-ODN. The data suggest that this procedure generates a novel and unique
      vaccine that rapidly triggers strong humoral and cell-mediated immunity.

PMID- 10940884
TI  - Extrathymic signals regulate the onset of T cell repertoire selection.
AB  - The thymus is the principal site of T cell development, coordinating positive and
      negative selection of an immunocompetent repertoire. The ability of fetal thymi
      from C57BL/6 mice to support these selection events in culture is, however,
      critically dependent on the timing of their excision: whereas thymi from 16 day
      embryos generate mature CD4+8(-) and CD4(-)8+ thymocytes, 14 day thymi show a
      profound blockage in positive selection at the CD4+8+ stage. Here we show that
      this blockage is not due to intrinsic deficiencies in the ability of thymocytes
      to transduce positive selection signals, suggesting the defect to lie within the
      thymic microenvironment. Since vascularization of the thymus occurs at day 15 of
      gestation, we investigated whether the exclusion of plasma proteins from 14 day
      thymi was responsible. Accordingly, the addition of serum from 16 day embryos to
      organ cultures of 14 day thymi rescued mature CD4+8(-) and CD4(-)8+ subsets.
      Activity was found to reside in a low molecular weight fraction of serum,
      sensitive to proteolysis, which was present only transiently during ontogeny. Our
      data suggest that repertoire selection is initiated following "priming" of the
      thymic microenvironment by plasma proteins, thereby ensuring the onset of
      positive selection to be delayed until the entry of extrathymic proteins to which
      self tolerance must be established.

PMID- 10940885
TI  - Compromised anti-tumor responses in tumor necrosis factor-alpha knockout mice.
AB  - The response of lymphokine-activated killer (LAK) and natural killer (NK) cells
      from mice lacking tumor necrosis factor-alpha (TNF-alpha-/- mice) was impaired in
      cytotoxicity assays against various tumor cell targets. Furthermore, allogeneic
      cytotoxic T lymphocyte (CTL) responses were also impaired as compared to TNF
      alpha+/+ littermates (control mice). Cytotoxicity was restored both upon in vitro
      incubation of TNF-alpha-/- lymphocytes with recombinant TNF-alpha (rTNF-alpha) or
      upon in vivo treatment of TNF-alpha-/- mice with rTNF-alpha. Using combinations
      of monoclonal antibodies we were able to show that TNF-alpha-/- effector
      lymphocytes exhibit both perforin- and Fas ligand-based cytotoxicity.
      Furthermore, upon in vivo administration of rTNF-alpha these effectors, in
      addition to perforin and Fas ligand, are also armed with TNF-alpha cytotoxic
      molecules, thus resembling to the cytotoxic effectors from control mice. In a
      tumor model, immunized TNF-alpha-/- mice failed to reject the syngeneic
      fibrosarcoma MC57X, but did so when injected with rTNF-alpha. In vivo
      administration of anti-TNF-alpha mAb neutralized the effect of rTNF-alpha
      supporting the growth of MC57X cells. Our data provide novel evidence for TNF
      alpha as an essential factor in (i) controlling cytotoxicity in vitro and in vivo
      and (ii) promoting tumor rejection in vivo.

PMID- 10940886
TI  - CpG ODN-mediated regulation of IL-12 p40 transcription.
AB  - Oligodeoxynucleotides (ODN) containing CpG motifs activate RAW 264.7 mouse
      macrophages and RPMI 8226 human myeloma cells to produce IL-12 p40. Using
      deletion and site-directed mutagenesis, the nuclear factor (NF)-kappaB half-site
      and the CCAAT/enhancer binding protein (C/EBP) recognition site were identified
      as potent cis-acting elements in CpG ODN-mediated IL-12 p40 promoter activation.
      Several NF-kappaB/Rel proteins competed for binding to the NF-kappaB half-site.
      The p65/c-Rel and p65/p50 heterodimer occupied this site shortly after CpG ODN
      administration (0.5-2 h), while the p50/c-Rel heterodimer dominated binding in
      the late stage (8-12 h). The induction of p50/c-Rel heterodimer was associated
      with a significant expression of IL-12 p40 mRNA. C/EBPbeta also contributed to
      CpG ODN-mediated IL-12 p40 promoter activation.

PMID- 10940887
TI  - Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as
      adjuvants for Th2 responses.
AB  - Infections with parasitic helminths such as Nippostronglyus brasiliensis induce
      dominant type 2 responses from antigen-specific T helper cells. The potency of
      the Th2 bias can also drive Th2 responses to bystander antigens introduced at the
      same time as infection. We now report that the Th2-promoting effect of infection
      can be reproduced with soluble N. brasiliensis excretory-secretory proteins (NES)
      released by adult parasites in vitro. Immunization of BALB/c mice with NES
      results in the production of IL-4 with elevated total serum IgE and specific IgG1
      antibodies. NES is also able to stimulate IL-4 and polyclonal IgE production in
      other mouse strains (C57BL/6, B10.D2, CBA). These features are seen whether NES
      is administered without adjuvant as soluble protein in phosphate-buffered saline
      or with complete Freund's adjuvant which normally favors Th1 responses. Thus, NES
      possesses intrinsic adjuvanticity. Moreover, co-administration of hen egg
      lysozyme (HEL) with NES in the absence of other adjuvants results in generation
      of HEL-specific lymphocyte proliferation, IL-4 release and IgG1 antibody
      responses, documenting that NES can act as an adjuvant for third-party antigens.
      Proteinase K digestion or heat treatment of NES before immunization abolished the
      IL-4-stimulating activity, indicating that the factors acting to promote Th2
      induction are proteins secreted by the adult parasite.

PMID- 10940888
TI  - Developmentally regulated and lineage-specific rearrangement of T cell receptor
      Valpha/delta gene segments.
AB  - To quantitate the frequency of Valpha/delta gene utilization by TCRgammadelta T
      cells we have generated a large panel of gammadelta T cell hybridomas and
      characterized their productive VDJ rearrangements. Using three novel mAb specific
      for the Vdelta5 chain and for several members of the Vdelta6 subfamily together
      with previously described Valpha- and Vdelta-specific mAb we have also
      quantitated the frequency of gammadelta and alphabeta cells expressing those
      Valpha/delta gene segments and located in different anatomical sites. We have
      also characterized the members of the Vdelta7/ADV10 subfamily expressed in
      C57BL/6 mice and analyzed the representation of individual ADV10 gene segments in
      alphabeta and gammadelta cells, as well as in precursor cells, in a situation in
      which TCR-dependent selection is negligible. Our results show that (i) although
      many Valpha/delta gene segments have the potential to rearrange to either Ddelta
      and Jdelta segments or to Jalpha segments, only a limited number of Valpha/delta
      gene segments are expressed by a quantitatively important fraction of gammadelta
      cells; (ii) such restricted usage of a limited number of Vdelta gene segments by
      gammadelta cells is mainly established at the level of V(D)J rearrangement, and
      (iii) there is very little overlap between Valpha/delta gene segments expressed
      by gammadelta and alphabeta cells.

PMID- 10940889
TI  - In vivo administration of IL-18 can induce IgE production through Th2 cytokine
      induction and up-regulation of CD40 ligand (CD154) expression on CD4+ T cells.
AB  - IL-18 is considered to be a strong cofactor for CD4+ T helper 1 (Th1) cell
      induction. We have recently reported that IL-18 can induce IL-13 production in
      both NK cells and T cells in synergy with IL-2 but not IL-12, suggesting IL-18
      can induce Th1 and Th2 cytokines when accompanied by the appropriate first
      signals for T cells. We have now found that IL-18 can act as a cofactor to induce
      IL-4, IL-10 and IL-13 as well as IFN-gamma production in T cells in the presence
      of anti-CD3 monoclonal antibodies (mAb). IL-18 can rapidly induce CD40 ligand
      (CD154) mRNA and surface expression on CD4+ but not CD8+ T cells. The
      administration of IL-18 alone in vivo significantly increased serum IgE levels in
      C57BL/6 (B6) and B6 IL-4 knockout mice. Furthermore, the administration of IL-18
      plus IL-2 induced approximately 70-fold and 10-fold higher serum levels of IgE
      and IgG1 than seen in control B6 mice, respectively. IgE and IgG1 induction in B6
      mice by administration of IL-18 plus IL-2 was eliminated by the pretreatment of
      mice with anti-CD4 or anti-CD154, but not anti-CD8 or anti-NK1.1 mAb. These
      results suggest that IL-18 can induce Th2 cytokines and CD154 expression, and can
      contribute to CD4+ T cell-dependent, IL-4-independent IgE production.

PMID- 10940890
TI  - Maintenance of IL-12-responsive CD4+ T cells during a Th2 response in Leishmania
      major-infected mice.
AB  - BALB/c and anti-IL-12-treated C3H mice infected with Leishmania major develop a
      Th2 cell response. However, in contrast to BALB/c mice, C3H mice treated
      transiently with an anti-IL-12 monoclonal antibody switch from a Th2 to a Th1
      response and resolve their lesions once treatment is terminated. We report here
      that the critical difference in the Th2 response between BALB/c and C3H mice is
      in their ability to respond to IL-12. Thus, C3H mice with a Th2 response maintain
      a CD4+ T cell population that expresses IL-12 receptor beta1 and beta2 mRNA and
      produces IFN-gamma after exposure to IL-12. These results indicate that Th2 cell
      populations from different genetic backgrounds differ in their stability, and
      that this difference can be related to differential regulation of the IL-12
      receptor.

PMID- 10940892
TI  - Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility
      locus involving the CD72c allele.
AB  - An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr),
      composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops
      systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ
      lpr/lpr (C3H/lpr) strain does not. In a genome-wide screening of the MRL
      background genes mediating susceptibility to collagen diseases using N2 progeny
      mice MRL/lpr x (MRL/lpr x C3H/lpr)F1, we previously found that each collagen
      disease is controlled by a different set of genes. To clarify the candidate genes
      for vasculitis, we extended the linkage analysis of renal vasculitis to a larger
      number of N2 mice and to F2 intercross mice. Two distinct recessive
      susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89
      and D4Mit147 in both progenies. The former was a novel locus for lupus
      phenotypes, which involved the MRL allele CD72(c) in contrast to the C3H allele
      CD72(b). The one on Chr 3 was a recessive locus which had an inhibitory effect on
      vasculitis. From their composition these loci seemed to be derived from AKR/J
      (for one) and LG/J (for another two) strains, and appeared to act in an additive
      manner on the development of vasculitis, indicating that vasculitis in MRL/lpr
      mice is inherited in a polygenic manner.

PMID- 10940891
TI  - Structure-function analysis of a lupus anti-DNA autoantibody: central role of the
      heavy chain complementarity-determining region 3 Arg in binding of double- and
      single-stranded DNA.
AB  - To determine the contribution of the somatic point mutations and that of the
      complementarity-determining region (CDR)3 Arg to DNA binding, we engineered the
      germline V(H) and V(kappa) gene revertant and site-mutagenized the CDR3 Arg
      residues of the mutated and "antigen-selected" mAb 412.67. This anti-DNA
      autoantibody was derived from B-1 cells of a lupus patient and bore two H-CDR3
      Arg, Arg105 and Arg107, encoded by N segment additions, and one kappa-CDR3 Arg,
      Arg97, resulting from a point mutation (Kasaian et al. 1994. J. Immunol. 152:
      3137-3151; Kasaian et al. 1995. Ann. N.Y Acad. Sci. 764: 410-423). The germ-line
      revertant bound double-stranded (ds) DNA and single-stranded (ss) DNA as
      effectively as its wild-type counterpart (relative avidity: 6.4x10(-7) and
      9.9x10(-9) vs. 6.7x10(-7) and 9.1 x10(-9) g/microl), raising the possibility that
      an antigen other than DNA was responsible for the selection of the mAb 412.67
      V(H) and V(kappa) point mutations. H-CDR3 Arg105 and Arg107 were both required
      for dsDNA binding, but either Arg105 or Arg107 was sufficient for ssDNA binding.
      The central role of Arg105 and Arg107 in DNA binding reflected their solvent
      exposed orientation at the apex of the H-CDR3 main loop. Consistent with its
      inward orientation afar from the antigen-binding surface, the kappa-CDR3 Arg97
      played no role in either dsDNA or ssDNA binding.

PMID- 10940893
TI  - Accelerated autoimmunity and lupus nephritis in NZB mice with an engineered
      heterozygous deficiency in tumor necrosis factor.
AB  - Development of autoimmunity and lupus nephritis in New Zealand (NZB x NZW)F1
      mice, a model for human systemic lupus erythematosus (SLE), involves both MHC-
      and non-MHC-linked contributions. A characteristic reduced responsiveness of the
      Tnf gene, which derives from the NZW parent, has been considered contributory
      since replacement therapy modifies the course of disease. It has remained unclear
      whether imbalances in TNF production operate early at the level of autoimmune
      induction, or, whether TNF interferes with the development of glomerulonephritis
      independent of the ensuing autoimmunity. To directly assess if reduced TNF
      production alone is sufficient to exacerbate the innocuous autoimmune responses
      present in NZB mice, we crossed NZB mice with Tnf-deficient and normal background
      control mice. Unlike control groups, (NZB x Tnf(0))F1 hemizygous mice develop
      enhanced autoimmunity and severe renal disease similar to the (NZB x NZW)F1 mice.
      Autoimmune responses are associated with an early spontaneous increase in serum
      levels of anti-nuclear autoantibodies and hyperproliferating B cells which
      readily express anti-dsDNA specificities in response to polyclonal and T helper
      stimuli. These findings demonstrate a physiological role for TNF in suppressing
      the emergence of autoreactive lymphocytes in the NZB model, and indicate that
      defective TNF function may be causative of the autoimmune and pathological
      phenomena in lupus.

PMID- 10940894
TI  - Beta-chemokines inhibit activation-induced death of lymphocytes from HIV-infected
      individuals.
AB  - The present study investigates the role of the HIV-suppressive beta-chemokines
      macrophage inflammatory protein (MIP)-1alpha, MIP-1 and RANTES in activation
      induced cell death (AICD). A pool of these beta-chemokines reduced anti-CD3
      induced apoptosis of T cell blasts from healthy blood donors in a dose-dependent
      manner. Although the pooled beta-chemokines were more effective, the inhibitory
      effect could also be mediated by each of the individual chemokines and was
      blocked by neutralizing anti-chemokine antibodies. The beta-chemokines also
      inhibited pokeweed mitogen/staphylococcal enterotoxin B-induced T lymphocyte
      apoptosis in 33/49 HIV-infected (HIV+) individuals. This anti-apoptotic effect
      was not correlated with the patients' CD4 T cell counts. beta-chemokines did not
      lead to altered secretion of IL-2, IL-4, IFN-gamma or IL-10 in response to
      activation stimuli in either normal T cell blasts or peripheral blood mononuclear
      cells from HIV+ individuals. Co-incubation with beta-chemokines did not inhibit
      anti-CD3-induced expression of cell surface Fas ligand, nor did it alter levels
      of the death receptor Fas or Bcl-2 in T cell blasts, suggesting that the beta
      chemokines are blocking AICD downstream of Fas. These observations indicate that
      beta-chemokines may play a novel role as modulators of AICD, in addition to their
      known role as chemoattractants and inhibitors of HIV replication.

PMID- 10940895
TI  - The antigen dose determines T helper subset development by regulation of CD40
      ligand.
AB  - Although the amount of antigen and the strength of T cell stimulation have been
      suggested to regulate Th1 vs. Th2 polarization, it remains unclear how the
      antigen dose and the strength of signal is detected by the T cell and translated
      into differential cytokine production. Using co-cultures of dendritic cells (DC)
      and ovalbumin (OVA)-specific CD4+ T cells obtained from RAG-2)(-/-) DO11.10 mice,
      we show here that high-dose antigen induced Th1 development by up-regulation of
      CD40 ligand (CD40L), whereas low-dose antigen stimulation failed to induce CD40L
      and promoted Th2 development. CD40-CD40L interaction was essential for IL-12
      production by DC. In the absence, de novo IL-4 production by T cells and
      autocrine Th2 development was induced. Furthermore, our results demonstrate that
      LFA-1/ ICAM interaction promotes Th1 differentiation by lowering the antigen dose
      required for CD40L up-regulation. Thus, we propose that (1) peptide-MHC density
      and (2) accessory molecules such as LFA-1 determine T helper polarization by
      regulation of CD40L.

PMID- 10940896
TI  - Epstein-Barr virus-dependent lymphoproliferative disease: critical role of IL-6.
AB  - Epstein-Barr virus (EBV)-induced lymphoproliferative disease (lpd) is a B cell
      neoplasm that affects patients who are immunosuppressed in the context of organ
      transplantation or HIV infection. A model for the aggressive form of this entity
      was generated by xenotransplantation of SCID mice with human peripheral blood
      leukocytes from individuals with prior contact with EBV. This model, where large
      B cell lymphoma occurs, was used to test the hypothesis that IL-6 has a major
      role in EBV-induced B cell tumorigenesis. IL-6 is known to differentiate B cells
      into immunoglobulin-secreting plasma cells and induce EBV replication, and
      xenochimeric animals have detectable serum levels of human IL-6. Human IL-6
      inhibition with a neutralizing monoclonal antibody decreased tumor incidence from
      62 % to 27 %. In addition, anti-IL-6 treatment significantly improved
      xenotransplanted animal survival, with median survival at > 245 days when
      compared to that of controls at 132 days. In conclusion, IL-6 plays a critical
      role in the pathogenesis of EBV-induced human lpd, and IL-6 inhibition may
      represent a new and promising preventive or therapeutic approach against this
      malignancy.

PMID- 10940897
TI  - Clonal analysis of NK cell development from bone marrow progenitors in vitro:
      orderly acquisition of receptor gene expression.
AB  - In the mouse, two families of MHC class I-specific receptors, namely Ly49 and
      CD94/NKG2, have been identified on NK cells. Individual NK cells can express
      several Ly49 molecules as well as members of the CD94/NKG2 family. The expression
      of multiple receptors with different specificities for MHC class I is thus
      thought to generate NK cells with diverse recognition patterns. To delineate the
      mechanism by which NK cells begin to express different patterns of Ly49 and
      CD94/NKG2 molecules, we developed a clonal assay in which NK1.1(-), IL-2/ IL-15
      receptor beta+ NK precursors generated by culture of multipotential Lin(-), c
      kit+ progenitors in IL-7, stem cell factor and flt3 ligand are induced to
      differentiate into NK1.1+ , Ly49+ NK cells. Examination of the clonal populations
      thus generated revealed heterogeneity in the pattern of Ly49 and CD94/NKG2 gene
      expression. In addition, a distinct kinetic pattern of expression was observed.
      CD94, NKG2A, NKG2C and Ly49B were expressed first followed by Ly49G, then Ly49C
      and I and finally, Ly49A, D, E and F. The data suggest a stochastic but ordered
      acquisition of class I receptors on NK cells in which developing NK cells become
      capable of expressing distinct receptors at different times but show no absolute
      prerequisite to express the receptors that are acquired early in NK development
      for the expression of those that are acquired later.

PMID- 10940898
TI  - Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent.
AB  - Female IL-4 knockout (KO) mice on a C57BL/6 background (F4KOC57) are susceptible
      to infection with the cecal-dwelling nematode Trichuris muris whereas wild-type
      C57BL/6 mice are resistant and expel the parasite. In this study we show that in
      sharp contrast, female IL-4 KO mice on a BALB/c background (F4KOB/c) are
      resistant to infection as are wild-type BALB/c mice. Although susceptible F4KOC57
      make negligible levels of all type 2 cytokines, resistant F4KOB/c were capable of
      producing significant levels of antigen-specific IL-13 (a cytokine shown to be
      critical in resistance to T. muris). To examine if the IL-13 in F4KOB/c mice was
      of functional importance, it was neutralized in vivo using a fusion protein, A25
      (sIL-13 R.Fc). The results presented here clearly demonstrate that neutralization
      of IL-13 in vivo did indeed prevent T. muris expulsion in normally resistant
      F4KOB/c mice. In addition, administration of recombinant mouse IL-13 to normally
      susceptible male IL-4KO BALB/c mice (M4KOB/c) caused an 87.85 % reduction in worm
      burden. Collectively, these data show that IL-13 is important in the poorly
      understood effector mechanisms resulting in the expulsion of T. muris from the
      gut. Moreover, the present data highlight the functional importance of gender and
      background strain in interpretation of studies using gene-targeted animals.

PMID- 10940899
TI  - A novel population of B7-1+ T cells producing intracellular IL-4 is decreased in
      patients with multiple sclerosis.
AB  - We identified a novel population of human T cells, studied directly ex vivo, that
      co-express surface B7-1 and intracellular IL-4. These peripheral blood B7-1+/CD4+
      T cells expressed cell surface molecules associated with differentiation
      including CD45RO and MHC class II, yet were CD69(-) and CD25(-). In short-term
      cultures, T cell receptor (TCR) cross-linking induced further IL-4 production
      with little IFN-gamma or TNF-alpha. In marked contrast, CD4+ T cells negative for
      B7-1 expressed intracellular IFN-gamma and high amounts of TNF-alpha but little
      IL-4 upon TCR cross-linking. The CD4+/B7-1+/IL-4-expressing T cells were of
      polyclonal origin based on their diverse TCR repertoire. To explore the
      biological significance of this B7-1+/IL-4+ T cell population and to assess its
      potential regulatory role in autoimmune disease, we examined whether these T
      cells isolated ex vivo were altered in subjects with multiple sclerosis (MS).
      While the frequency of B7-1+ T cells was enhanced in patients with MS as compared
      to normal subjects, there was a significant diminution of B7-1+/IL-4+ T cells in
      the patients. The decrease in these IL-4-producing T cells in patients with
      autoimmune disease is consistent with a possible role as immunoregulatory T
      cells.

PMID- 10940900
TI  - The effect of TGF-beta1 on immune responses of naive versus memory CD4+ Th1/Th2 T
      cells.
AB  - The role of TGF-beta1 in the regulation of T cell responses has been perplexing,
      possibly because it is dependent on the type of T cell being regulated and its
      cytokine microenvironment. In the present study, we demonstrate that TGF-beta1
      has a profound inhibitory effect on naive CD4+ T cell undergoing differentiation
      under defined neutral, Th1 and Th2 priming conditions. In addition, we show that
      if CD4+ T cells are primed in the presence of TGF-beta1, they exhibit reduced
      secondary anti-CD3/anti-CD28-induced and antigen-specific immune responses (even
      when TGF-beta is absent during the secondary response), which is not due to
      reduced expression of co-stimulatory molecules or to inadequate IL-2 production.
      Finally, with respect to the effect of TGF-beta on fully differentiated antigen
      specific memory CD4+ T cells, we demonstrate that while antigen-specific
      activation and cytokine secretion by memory Th1 T cells is inhibited by TGF
      beta1, such inhibition is associated with partial down-regulation of IL-12
      receptor beta2 chain expression. In contrast, memory Th2 T cells are not subject
      to TGF-beta1 -mediated suppression. In summary, these studies reveal that TGF
      beta1 is a powerful negative regulator of the primary immune response of CD4+ T
      cells, but only Th1 T cells are subject to such regulation after the memory stage
      of T cell differentiation has been reached. Thus, these studies define the
      potential regulatory role of TGF-beta1 in Th1 and Th2 T cell-mediated
      autoimmunity.

PMID- 10940901
TI  - Synthetic insertion signal sequences enhance MHC class I presentation of a
      peptide from the melanoma antigen MART-1.
AB  - Cytotoxic T lymphocytes (CTL) recognize minimal peptides of eight to ten residues
      which are the products of intracellularly processed proteins and are presented at
      the cell surface by MHC class I molecules. An important step in this process is
      the translocation of processed proteins from the cytosol across the endoplasmic
      reticulum membrane mediated by transporter associated with antigen processing
      (TAP) proteins, or as an alternative, by endoplasmic reticulum insertion signal
      sequences. We report here that the addition of synthetic signal sequences at the
      N terminus, but not at the C terminus, of an epitope from the human melanoma
      antigen MART-1 greatly enhances its presentation in both TAP-deficient and TAP
      expressing cells. A newly designed peptide construct, composed of the epitope
      replacing the hydrophobic part of a natural signal sequence, was also very
      effective. Interestingly, an artificial signal sequence containing the same
      epitope was the most efficient construct for enhancing its presentation. These
      peptide constructs facilitated epitope presentation when loaded into the cytosol
      of TAP-deficient T2 cells, TAP-expressing melanoma cells and human dendritic
      cells. These findings may be of practical significance for the development of
      synthetic anti-cancer vaccines and in vitro immunization of CTL for adoptive
      immunotherapy.

PMID- 10940902
TI  - Studies on the role of IL-7 presentation by mesenchymal fibroblasts during early
      thymocyte development.
AB  - T cell precursor development depends upon poorly defined interactions between
      thymocyte precursors and stromal cells involving cell surface molecules,
      extracellular matrix (ECM) components and soluble growth factors. To determine
      whether presentation of soluble factors by ECM is involved in early T cell
      development, we analyzed expression of ECM components in individual thymic
      stromal subsets and investigated their ability to present ECM-associated IL-7, a
      factor known to be important during early thymocyte development. We show that MHC
      class II(+) thymic epithelium and fibroblasts - essential requirements for
      development of CD4(-)8(-)precursors - both show surface expression of ECM
      components such as fibronectin and heparan sulfate. Use of biotinylated IL-7
      protein indicates that both cell types bind IL-7, while enzymatic disruption of
      specific ECM components indicates that IL-7 presentation by both cell types is
      dependent upon heparan sulfate. However, disruption of IL-7 presentation
      specifically on fibroblasts does not affect their ability to contribute to T cell
      development. Collectively, these data suggest that while ECM-mediated
      presentation of IL-7 may be a general function of thymic stromal cells during
      thymocyte development, heparan sulfate-mediated IL-7 presentation specifically by
      fibroblasts is not essential and that the specific requirement for fibroblasts in
      early development involves additional undefined interactions.

PMID- 10940903
TI  - CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP
      (OX41) and human SIRPalpha 1.
AB  - The rat OX41 antigen is a cell surface protein containing three immunoglobulin
      superfamily domains and intracellular immunoreceptor tyrosine-based inhibitory
      motifs (ITIM). It is a homologue of the human signal-regulatory protein (SIRP)
      also known as SHPS-1, BIT or MFR. Cell activation-induced phosphorylation of the
      intracellular ITIM motifs induces association with the tyrosine phosphatases SHP
      1 and SHP-2. To identify the physiological OX41 ligand, recombinant OX41-CD4d3+4
      fusion protein was coupled to fluorescent beads to produce a multivalent cell
      binding reagent. The OX41-CD4d3+4 beads bound to thymocytes and concanavalin A
      stimulated splenocytes. This interaction was blocked by the monoclonal antibody
      (mAb) OX101. Affinity chromatography with OX101 mAb and peptide sequencing
      revealed the rat SIRP ligand to be CD47 (integrin-associated protein). A direct
      interaction between human SIRP and human CD47 was demonstrated using purified
      recombinant proteins and surface plasmon resonance ruling out the involvement of
      other proteins known to be associated with CD47. The affinity of the SIRP/CD47
      interaction was K(d) approximately 8 microM at 37 degrees C with a k(off )>/=2.1
      s(-1). The membrane-distal SIRP V-like domain was sufficient for binding to CD47.

PMID- 10940904
TI  - Cytokines production of U5A2-13-positive T cells by stimulation with glycolipid
      alpha-galactosylceramide.
AB  - We have previously established and reported a novel monoclonal antibody (mAb),
      U5A2-13, which recognizes a phenotypically similar population of natural killer
      (NK)-like T cells. Using U5A2-13 mAb, we now describe the functional properties
      of U5A2-13(+) T cells in both NK1.1-positive or -negative mouse strains. Similar
      to NK1.1(+) T cells, hepatic U5A2-13(+) T cells of C57BL/6 (NK1.1(+) strain)
      mice, but not U5A2-13(-) T cells, could be induced to produce large amounts of IL
      4 and IFN-gamma by stimulation with glycolipid alpha-galactosylceramide (alpha
      GalCer) present on dendritic cells (DC) in a dose-dependent manner. The abundant
      production of these cytokines from U5A2-13(+) T cells of BALB/c (NK1.1(-) strain)
      mice is similar to that noted in C57BL/6 mice. Cytokine production by cultures
      stimulated with DC of beta2-microglobulin-deficient mice was significantly less
      than that of cultures stimulated with DC of intact mice. Overall, U5A2-13(+) T
      cells recognize alpha-GalCer presented by CD1d, indicating that U5A2-13(+) T
      cells can be used to analyze NK-like T cell function in various strains of mice.

PMID- 10940905
TI  - Association of signal-regulatory proteins beta with KARAP/DAP-12.
AB  - The signal-regulatory proteins (SIRP) are Ig-like cell surface receptors detected
      in hematopoietic and non-hematopoietic cells. SIRP are classified as SIRPalpha
      molecules, containing a 110- to 113-amino acid long, or SIRPbeta molecules, with
      a 5-amino acid long intracytoplasmic domain. SIRPalpha molecules belong to
      inhibitory immunoreceptor tyrosine-based inhibition motif (ITIM)-bearing
      molecules. The majority of ITIM-bearing receptors are paired with activating
      isoforms, which share highly related extracytoplasmic domains but harbor a
      shorter cytoplasmic domain devoid of ITIM and contain a charged amino acid
      residue in their transmembrane domain. Activating receptors are associated with
      immunoreceptor tyrosine-based activation motif (ITAM)-bearing proteins, such as
      KARAP/DAP-12 and FcRgamma. In this report, we show that human SIRPbeta1 is
      included in an oligomeric complex with KARAP/DAP-12 in hematopoietic and non
      hematopoietic transfectant cells as well as in human monocytes. The physical
      association between SIRPbeta1 and KARAP/DAP-12 results in the functional coupling
      of SIRPbeta1 engagement to the recruitment of the protein tyrosine kinase Syk and
      to serotonin release in RBL cell transfectants. Therefore our results show that
      SIRPbeta1 acts as an activating isoform of SIRPalpha molecules, confirming the co
      existence of inhibitory ITIM-bearing molecules, recruiting SHP-1 and SHP-2
      protein tyrosine phosphatases, and activating counterparts, whose engagement
      couples to protein tyrosine kinases via ITAM-bearing molecules.

PMID- 10940906
TI  - Biallelic expression of the IL-2 locus under optimal stimulation conditions.
AB  - Recent experiments have suggested that the IL-2 locus is monoallelically
      expressed. We tested this hypothesis using TCR-transgenic mice carrying one
      inactivated IL-2 allele. The frequency in single-cell assays of IL-2-producing
      cells following optimal stimulation by antigen and antigen-presenting cells was
      equivalent to that from wild-type mice, but the amount of IL-2 produced per cell
      was twofold less. Similar observations were made by intracellular staining for IL
      2, although stimulation in bulk culture was less optimal, showing only a 1.7-fold
      difference. Importantly, the frequency of responding cells from the heterozygotes
      was less than from the wild-type mice if the IL-2 assay was performed after only
      24 - 30 h of activation, suggesting that the targeted allele could compete with
      the normal allele early after stimulation and give the misimpression that the
      heterozygotes had fewer IL-2-producing cells. These data strongly argue that the
      IL-2 locus can be expressed biallelically under optimum stimulation conditions.

PMID- 10940907
TI  - Induction of experimental autoimmune arthritis by a public epitope of the T cell
      receptor variable alpha domain of an arthritogenic T cell clone.
AB  - T cell receptor (TCR) peptide immunizations have been demonstrated to protect
      against experimental autoimmune diseases. These findings have led to clinical
      trials employing TCR peptides in multiple sclerosis and rheumatoid arthritis
      patients. Previously, we identified a strongly immunogenic region of the TCR
      alpha chain of an arthritogenic T cell clone (AV11 66-80). In this report, we
      show that rats immunized with AV11 66-80 developed arthritis with clinical
      symptoms and histology similar to adjuvant arthritis (AA). Transfer of this
      disease into naive rats using AV11 66-80-specific T cells proved the T cell
      mediated character of the disease. The AV11 66-80 arthritic rats developed
      resistance to Mycobacterium tuberculosis-induced AA, indicating that both forms
      of arthritis depended on similar regulatory mechanisms. This first demonstration
      of TCR peptide-induced arthritis, together with an earlier report on a
      polymorphism in this very same AV11 66-80 region involved in arthritis resistance
      in mice, suggests a central role of the public epitope AV11 66-80 in the control
      of autoimmune arthritis. Although TCR peptide immunizations can be exploited to
      prevent experimental autoimmunity, caution should be taken in the induction of
      TCR peptide-specific T cells for immunotherapy to avoid adverse effects as shown
      here.

PMID- 10940908
TI  - Engagement of CD30 shapes the secretion of cytokines by human gamma delta T
      cells.
AB  - CD30 is a member of the TNF receptor superfamily, previously shown to be
      expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We
      here show that CD30 is highly expressed on recently activated human gamma delta T
      cells. Elevated surface levels of this molecule persisted in long-term cultures
      of gamma delta cells, without further cell stimulation. CD30 acted as a co
      stimulus in gamma delta T cells by potentiating the intracellular Ca(2+) fluxes
      induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of
      several cytokines induced upon CD3 stimulation such as IL-4 and IFN-gamma but not
      IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1beta were
      constitutively expressed and not affected by stimulation. The inducible
      expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co
      stimulation, as well as that of the CC chemokines I-309 and MDC, whereas the
      secretion of the monocyte chemotactic protein-1 was not detected. Triggering of
      CD30 may therefore modulate the expression of several cytokines released by gamma
      delta cells; the expression of its physiologic ligand by APC and neutrophils at
      the site of infection may contribute to determine the outcome of an immune
      response.

PMID- 10940909
TI  - B cell positive selection by self antigens and counter-selection of dual B cell
      receptor cells in the peripheral B cell pools.
AB  - The presence of B cells expressing two B cell receptors (BCR), described in BCR
      transgenic, gene-targeted and normal mice, may represent an autoimmune hazard. We
      generated RAG-2-deficient mice bearing two complete rearranged immunoglobulin
      transgenes. In these mice most mature resting B cells express chains from the two
      transgenes. We studied selection of these dual receptor B cells in the presence
      of self antigens. In spite of the reduced surface density of the anti-self
      receptor, self-reactive B cells are deleted in the presence of membrane-bound
      self antigens. In contrast, the presence of soluble self antigen positively
      selects single receptor B cells expressing the self-reactive receptor. At the
      periphery these positively selected B cells down-regulate surface IgM expression
      and become unresponsive. A few dual receptor cells, however, escape tolerance
      induction. We examined the peripheral fate of the dual receptor B cells and
      showed that they are poorly selected into the activated B cell compartment and
      show a poor competitive capacity when in presence of populations of single
      receptor B cells. These results indicate that peripheral selection contributes to
      the very low frequencies of dual receptor B cells in normal mice and that
      multiple safeguard mechanisms operate to minimize the autoimmune hazard that
      allelically included B cells could represent.

PMID- 10940910
TI  - B and T cell immune response to small nuclear ribonucleoprotein particles in
      lupus mice: autoreactive CD4(+) T cells recognize a T cell epitope located within
      the RNP80 motif of the 70K protein.
AB  - Systemic lupus erythematosus is characterized by the presence of high titers of
      autoantibodies reacting with various components of the U1 small nuclear
      ribonucleoprotein particle (snRNP). It has been suggested that these antibodies
      are produced by an antigen-driven mechanism under the dependence of antigen
      specific T cells. To investigate the role of T cell help in this process, we
      sought, with 20 overlapping peptides, the Th epitopes on the U1-70K snRNP in
      unprimed H-2(k) MRL / lpr lupus mice and immunized CBA normal mice. The peptide
      131 - 151 was recognized by both IgG autoantibodies and CD4(+) T cells from 7 - 9
      week-old MRL / lpr mice. In this test, antigen-presenting cells (APC) from MRL /
      lpr mice were required; APC from naive CBA mice failed to stimulate CD4(+) cells
      from MRL / lpr mice. The potential role of MRL / lpr B cells as APC, the
      expression of MHC class II molecules at their surface and their activation state
      (expression of CD69, CD80 / B7-1 and CD86 / B7-2 molecules) were studied. Peptide
      131 - 151 bound both I-A(k) and I-E(k) class II molecules and favored an IL-2
      positive T cell response but not IFN-gamma, IL-6 and IL-10 secretion. Segment 131
      - 151 is localized within the RNP80 motif and contains residues that are highly
      conserved in many nuclear, nucleolar and cytoplasmic RNA binding proteins.

PMID- 10940911
TI  - Characterization of T cell precursor activity in the murine fetal thymus:
      evidence for an input of T cell precursors between days 12 and 14 of gestation.
AB  - In the mouse, the number and the differentiation potential of thymic migrants
      remain controversial. A fetal thymic organ culture under limiting dilution
      conditions allowed us to show a 130-fold increase in the numbers of T cell
      precursors in the embryonic thymus between days 12 and 14 of gestation. A
      comparative analysis of the most immature thymocytes at these two stages revealed
      that: (1) CD44(+)CD25(-) (DN1) thymocytes at 14 days post coitum (dpc)
      efficiently differentiate into mature T cells both in vivo and in vitro; (2)
      12dpc thymocytes exhibit a low frequency of T cell precursors and were unable to
      generate a detectable progeny after in vivo intrathymic transfer. A 48-h organ
      culture of 12dpc thymic lobes did neither correct the low frequency of T cell
      precursors nor the absence of expression of T cell-specific genes observed in
      12dpc thymocytes. We thus concluded that a fraction of recent thymic immigrants
      contribute to the observed properties in DN1 14dpc thymocytes. We show that
      increasing numbers of T cell precursors migrate to the thymus from 11 to 14 dpc.
      We propose that the first thymic immigrants do not contribute significantly to T
      cell generation which depends on the subsequent colonization by cells with a high
      T cell precursor potential.

PMID- 10940912
TI  - The heat shock protein gp96 induces maturation of dendritic cells and down
      regulation of its receptor.
AB  - Peptides associated with the heat shock protein gp96 induce a specific T cell
      response against cells from which gp96 is isolated. Recently, we have shown that
      gp96 binds to a yet unknown receptor present on dendritic cells (DC) and that
      receptor-mediated uptake is required for cross-presentation of gp96-associated
      peptides by DC. We now describe that gp96 mediates maturation of DC as determined
      by up-regulation of MHC class II and CD86 molecules, secretion of the cytokines
      IL-12 and TNF-alpha and enhanced T cell stimulatory capacity. Heat-denatured gp96
      is not able to induce DC maturation and cytokine secretion. Furthermore, we show
      that mature DC are no longer able to bind gp96 molecules. Hence, the gp96
      receptor is down-regulated on mature DC, suggesting that this receptor behaves
      similar to other receptors involved in antigen uptake like the scavenger receptor
      CD36, the mannose receptor or the integrins alpha(v)beta(3) and alpha(v)beta(5).
      Together, our findings provide an additional explanation for the remarkable
      immunogenicity of gp96 as a cross-priming antigen carrier and direct activator of
      DC.

PMID- 10940913
TI  - Identification of tumor-associated MHC class I ligands by a novel T cell
      independent approach.
AB  - Specific immunotherapy of cancer utilizes tumor-directed cytotoxic T lymphocytes
      (CTL) that lyse tumor cells presenting MHC class I-associated peptides derived
      from tumor-associated proteins. Many tumor-associated gene products are known,
      but corresponding T cell epitopes are only known for relatively few of these. The
      most commonly used approaches to identify such antigens require pre-existing CTL
      lines or clones. By using a CTL-independent high performance liquid
      chromatography mass spectrometry (HPLC MS)-based approach we identified HLA-A2
      presented peptides from carcinoembryonic antigen and wild-type p53 with a copy
      number as low as eight molecules per cell. Potential epitopes were predicted from
      the sequences of known tumor antigens and the corresponding synthetic peptides
      were analyzed by nanocapillary HPLC MS. In parallel, peptides were extracted from
      fresh, solid tumor tissue or tumor cell lines and analyzed in the same way. Upon
      co-elution of a natural peptide with a predicted peptide of the same mass, the
      peptide sequence was confirmed by on-line tandem MS. This approach allows rapid
      screening of large numbers of tumor-associated gene products for naturally
      processed peptides presented by different MHC class I molecules as a prerequisite
      for efficient epitope identification and rapid transfer to therapeutic vaccine
      trials.

PMID- 10940914
TI  - Antigen persistence is required for somatic mutation and affinity maturation of
      immunoglobulin.
AB  - Whether germinal centers (GC) with follicular dendritic cell (FDC) clusters are
      the essential sites for affinity maturation of immunoglobulin is still
      controversial. To re-evaluate the role of GC / FDC in affinity maturation and
      somatic mutation in a defined antigen system, lymphotoxin-alpha(- / -) and TNF
      receptor I(- / -) mice, lacking GC / FDC, were immunized with (4-hydroxy-3
      nitrophenyl) acetyl-sheep RBC (NP-SRBC). In contrast to soluble hapten-carrier
      systems, NP-SRBC allows us to compare affinity maturation in the presence or
      absence of adjuvant. These mice showed a dramatically impaired ability to
      generate high-affinity IgG to NP, but retained the ability to produce low
      affinity anti-NP IgG when NP-SRBC was used in the absence of adjuvant. In
      contrast to wild-type mice, somatic mutation of the expressed IgG heavy chain
      gene was rarely detected in these GC / FDC-deficient mice. This suggests that GC
      / FDC are essential for affinity maturation. Trapping antigen-specific B cells
      inside the T cell zone of TNFRI(- / -) mice may prolong the interaction between T
      and B cells, which allows class switching but no further affinity maturation of
      IgG. Interestingly, GC / FDC-deficient mice could be induced to generate high
      affinity, somatically mutated IgG antibodies by immunization with the same amount
      of NP-SRBC antigen emulsified in incomplete Freund's adjuvant or repeated
      immunization with the antigen alone. Thus, these data support a model in which
      prolonged availability of antigen is required for somatic mutation and affinity
      maturation, and FDC or adjuvants facilitate such processes by slowly releasing
      antigens.

PMID- 10940915
TI  - Leishmania donovani promastigotes evade the activation of mitogen-activated
      protein kinases p38, c-Jun N-terminal kinase, and extracellular signal-regulated
      kinase-1/2 during infection of naive macrophages.
AB  - The protozoan parasite Leishmania fails to activate naive macrophages for
      proinflammatory cytokines production, and selectively impairs signal transduction
      pathways in infected macrophages. Because mitogen-activated protein kinases
      (MAPK)- and NF-kappaB-dependent signaling pathways regulate proinflammatory
      cytokines release, we investigated their activation in mouse bone marrow-derived
      macrophages (BMM) exposed to Leishmania donovani promastigotes. In naive BMM, the
      parasite failed to induce the phosphorylation of p38 MAPK, c-Jun N-terminal
      kinase (JNK), and extracellular signal-regulated kinase (ERK)1/2, as well as the
      degradation of IkappaB-alpha. The use of L. donovani mutants defective in the
      biosynthesis of lipophosphoglycan revealed that evasion of ERK1/2 activation
      requires surface expression of the repeating unit moiety of this virulence
      determinant. In IFN-gamma-primed BMM, L. donovani promastigotes strongly induced
      the phosphorylation of p38 MAPK and ERK1/2, and the use of selective inhibitors
      for ERK (PD98059) and p38 MAPK (SB203580) revealed that both kinases are required
      for L. donovani-induced TNF-alpha but not NO(2)(-) release. Collectively, these
      data suggest that both p38 MAPK and ERK1/2 pathways participate in some
      Leishmania-induced responses in IFN-gamma-primed BMM. The ability of L. donovani
      promastigotes to avoid MAPK and NF-kappaB activation in naive macrophages may be
      part of the strategy evolved by this parasite to evade innate immune responses.

PMID- 10940916
TI  - The role of gammadelta T cells in generating antiviral factors and beta
      chemokines in protection against mucosal simian immunodeficiency virus infection.
AB  - In view of the role of gammadelta(+) T cells in mucosal protection against
      infection, the proportion of gamma delta T cells was examined in cells eluted
      from lymphoid and mucosal tissues of macaques immunized with simian
      immunodeficiency virus (SIV) gp120 and p27 in alum and challenged with live SIV
      by the rectal mucosal route. This revealed a significant increase in gammadelta T
      cells eluted from the rectal mucosa (p < 0.01) and the related iliac lymph nodes
      (p < 0.0001) in protected as compared with infected macaques. Preferential homing
      of PKH-26-labeled gammadelta(+) T cells from the primed iliac lymph nodes to the
      rectal and cervico-vaginal mucosa was demonstrated after targeted iliac lymph
      node as compared with i. m. immunization. Investigations of the mechanism of
      protection revealed that gammadelta(+) T cells can generate antiviral factors,
      RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta which can
      prevent SIV infection by binding to the CCR5 coreceptors. Up-regulation of
      gammadelta(+) T cells was demonstrated by immunization of macaques with heat
      shock protein (HSP)70 linked to peptides and with granulocyte-macrophage colony
      stimulating factor (GM-CSF). This was confirmed by in vitro studies showing that
      GM-CSF can up-regulate gammadelta(+) T cells from macaques immunized with HSP
      linked peptides but not those from naive animals. We suggest that a novel
      strategy of immunization with HSP70 linked to antigen may generate both cognate
      immunity to the antigen and innate immunity by virtue of up-regulation of
      gammadelta(+) T cells. These cells generate antiviral factors and the three beta
      chemokines that prevent binding and transmission of SIV or M-tropic HIV by the
      CCR5 coreceptor.

PMID- 10940917
TI  - Regulation of type 2 nitric oxide synthase by type 1 interferons in macrophages
      infected with Leishmania major.
AB  - We recently reported that the infection of macrophages with Leishmania major led
      to the release of type 1 interferons (IFN-alpha /beta ). Moreover, at day 1 of
      infection of mice with L. major, IFN-alpha /beta was required for the expression
      of type 2 (inducible) NO synthase (NOS2 or iNOS) which, however, was restricted
      to a few macrophages in the dermis. Here, we further characterized the regulation
      of NOS2 by IFN-alpha /beta. Macrophages that were either simultaneously or
      sequentially exposed to L. major promastigotes and IFN-alpha /beta expressed NOS2
      and anti-leishmanial activity. In contrast, when high amounts of IFN-alpha /beta
      were used or when IFN-alpha /beta was added to the macrophages 2 h prior to the
      parasites, almost no induction of NOS2 was observed. After pretreatment with IFN
      alpha /beta, tyrosine phosphorylation and nuclear DNA binding of Stat1alpha, the
      degradation of the NF-kappaB inhibitor (IkappaBalpha and beta), and the nuclear
      translocation of NF-kappaB were strongly impaired compared with macrophages
      exposed to IFN-alpha /beta and L. major simultaneously. Thus, IFN-alpha /beta
      exerts agonistic or antagonistic effects on the expression of NOS2 in macrophages
      infected with a microbial pathogen, depending on the sequence of the stimuli and
      the amount of IFN-alpha /beta added. The limited number of NOS2-positive
      macrophages at day 1 of infection in vivo might result from a blockage of non
      infected macrophages by IFN-alpha /beta that is released by neighboring infected
      cells.

PMID- 10940918
TI  - Induction or suppression of a B cell-specific response to self antigen in vivo is
      dependent upon dendritic cell activation via the TNF-alpha receptor at the time
      of antigen uptake.
AB  - In this study we show that the retinal autoantigen, S-antigen, contains a
      functional TNF-alpha homologous domain which stimulates maturation and
      differentiation of cultured dendritic cells (DC) or tissue DC via the p55 TNF
      alpha receptor. Tissue DC became more dendritiform in shape, and migrated into
      culture supernatant. S-antigen also stimulated accumulation of cell surface MHC
      class II antigen with a corresponding loss of acidic intracellular vesicles, and
      induced IL-1beta and IL-12 mRNA expression in cultured bone marrow-derived DC. In
      addition, cultured splenic DC primed immune responses to S-antigen in vivo in the
      absence of other, exogenous cytokine sources. DC pulsed with either retinal S
      antigen or another retinal autoantigen, interphotoreceptor retinoid binding
      protein (IRBP), were able to stimulate naive T cell proliferation in vitro, but
      only S-antigen-pulsed DC were able to induce an immune response in vivo and
      initiate antibody class switching. In contrast, IRBP-pulsed DC had no detectable
      in vivo priming effect and IgG antibody levels remained suppressed even after
      immunization with IRBP in complete Freund's adjuvant. These results indicate that
      DC from the same precursor population can either induce or suppress a B cell
      specific response to self antigen in vivo, the outcome being dependent upon DC
      activation at the time of antigen uptake and presentation.

PMID- 10940919
TI  - Identification in humans of HPV-16 E6 and E7 protein epitopes recognized by
      cytolytic T lymphocytes in association with HLA-B18 and determination of the HLA
      B18-specific binding motif.
AB  - Human papilloma virus type 16 (HPV-16) is the HPV most frequently associated with
      cervical carcinoma in humans. For the prevention or treatment of cervical
      carcinoma, the E6 and E7 oncoproteins appear to be good targets for vaccine
      induced cytotoxic T lymphocytes (CTL). Lipopeptide vaccination is an efficient
      way of stimulating cellular responses. However, to synthesize effective
      lipopeptides, it is necessary to define which epitopes are immunogenic. In this
      study we first determined that peptide 80 - 88 of the E6 protein was recognized
      by CTL from a healthy donor in association with the HLA-B18 molecule. We then
      defined the HLA-B18 anchoring peptide motif by testing the binding of various
      short peptides with the HLA-B18 molecule and showed that it was related to the
      HLA-A1-specific peptide motif. Furthermore, in analyzing the potential E7
      epitopes susceptible to associating with HLA-B18, we demonstrated that peptide E7
      44 - 52 gave the strongest binding. It could also be recognized by CTL from
      peripheral blood mononuclear cells (PBMC) of the same healthy donor. Finally,
      with PBMC from a patient with a cervical intraepithelial neoplasia grade 3, we
      found CTL which recognized the E6 80 - 88 epitope. We have hence identified two
      peptides encoded by the E6 and E7 proteins which are presented by the HLA-B18
      molecule and could be included in a vaccine against HPV-16.

PMID- 10940920
TI  - Negative regulation of autoreactive B cells in transgenic mice expressing a human
      pathogenic cold agglutinin.
AB  - Cold agglutinins (CA) are autoantibodies that bind to erythrocyte carbohydrates
      at low temperatures and induce complement-mediated cell lysis, thus causing
      hemolytic anemia. Tolerance mechanisms towards CA-expressing B cells and the
      factors inducing pathogenic CA production are unknown. In order to develop an
      animal model for CA disease, we have produced transgenic mice expressing the
      heavy or the light chain of a human CA, previously shown to be pathogenic to the
      mouse. Expression of the human H chain alone resulted in a B cell maturation
      block at the pro-B stage, and did not induce allelic exclusion. In double
      transgenic mice, co-expression of the human H and L chains restored B cell
      development but the majority of bone marrow cells expressing the human IgM were
      eliminated by deletion. In the periphery, B cells were depleted, and a large
      proportion of the remaining cells co-expressed a human and a murine H chain,
      secreting "mixed" IgM. A few autoreactive cells, predominating in the peritoneal
      cavity, escaped tolerance mechanisms and secreted transgenic IgM. The
      autoreactive B cells are amenable to polyclonal stimulation, making these
      transgenic mice a suitable model for a human autoimmune disease.

PMID- 10940921
TI  - Phenotypic characterization of CD8(+)NKT cells.
AB  - We describe a novel CD8(+)NKT cell population expressing TCRalpha /beta or
      TCRgamma /delta. These CD8(+)NKT cells were prominent in the liver, and except
      for the thymus, virtually absent in other lymphoid organs. CD8(+)NKT cells
      expressed activation markers and comprised a high proportion of Ly49(+) cells.
      The development of the majority of CD8(+)NKT cells expressing TCRalpha /beta, but
      not TCRgamma /delta, depended on classical MHC class I. No CD8(+)NKT cells were
      detectable in young athymic mice, whereas the cells expressing TCRgamma /delta,
      but not TCRalpha /beta, appeared randomly in aged athymic mice. CD8(+)NK1(+)
      TCRalpha /beta cells showed polyclonal TCRVbeta usage and were virtually devoid
      of TCRValpha14. CD8(+)NK1(+) TCRgamma /delta cells predominantly expressed
      TCRVgamma1, 2 and 4, and Vdelta4, 5, 6 and 7. CD8(+)NKT cells, in particular
      those expressing TCRgamma /delta, were a major population in early life. IFN
      gamma, but not IL-4, was induced in CD8(+)NKT cells by in vitro stimulation,
      independent of the TCRalpha /beta or TCRgamma /delta lineage. Hence, these cells
      represent a unique, though heterogeneous T cell population that shares markers
      with, but is distinct from, both conventional NKT cells and conventional CD8(+) T
      cells, and that may play a role in immune regulation.

PMID- 10940922
TI  - Distinct VH repertoires in primary and secondary B cell lymphocyte subsets in the
      preimmune repertoire of A/J mice: the CRI-A idiotype is preferentially associated
      with the HSA(low) B cell subset.
AB  - The anti-arsonate immune response of A/J mice is characterized by the occurrence
      of several recurrent idiotypes with a different temporal pattern of expression.
      The CRI-A idiotype is typically a memory idiotype since it appears late in the
      primary and dominates the secondary as well as subsequent immune responses. The
      CRI-C idiotype is present throughout the responses, including the primary one.
      Naive adult A/J mice treated repeatedly with anti-mu or anti-delta monoclonal
      antibodies exhibit a completely different balance of HSA(low) and HSA(high) B
      cell subsets and an opposite idiotype profile after immunization with p
      azophenylarsonate coupled to hemocyanin. Anti-mu treatment leads to a striking
      enhancement of the HSA(low) cell subset associated with an earlier important
      synthesis of CRI-A(+) antibodies, while anti-delta treatment enhances
      significantly the HSA(high) compartment with a strong decrease of CRI-A and
      persistence of CRI-C1 antibodies. Semiquantitative PCR analysis reveals that the
      presence of CRI-A transcripts is associated with the HSA(low) compartment, while
      CRI-C transcripts are mainly associated with HSA(high) B cell subsets. This has
      been demonstrated with spleen cells of adult A/J mice treated with anti-mu or
      anti-delta antibodies and also with purified B cell subsets of unimmunized adult
      A/J mice and on neonatal spleen cells. It appears that the memory (CRI-A)
      idiotype is selected into the HSA(low) B cell subset before antigen arrival.

PMID- 10940923
TI  - Mice lacking the transcription factor RelB develop T cell-dependent skin lesions
      similar to human atopic dermatitis.
AB  - Mice with a targeted disruption of the Rel / NF-kappaB family member RelB develop
      a complex inflammatory phenotype and hematopoietic abnormalities. RelB-deficient
      (relB(- / -)) mice were clinically normal until 4 - 10 weeks after birth when
      thickening of the skin and hair loss developed. Histological and
      immunohistochemical evaluation of relB(- / -) skin lesions revealed
      hyperkeratosis and marked epidermal hyperplasia. Many CD4(+) T cells and
      eosinophils mixed with lesser numbers of CD8(+) T cells and neutrophils were
      present in the dermis. There was a moderate increase of MHC class II-positive
      dermal dendritic cells and dermal mast cells. Increased expression of Th2
      cytokines correlated with increased mRNA levels of eotaxin and CCR3 in relB(- / 
      ) skin. The dermatitis did not develop in the offspring of relB(- / -) mice
      crossed with transgenic mice that lack peripheral T cells, demonstrating that the
      skin lesions were T cell dependent. The dermatitis observed in RelB-deficient
      mice had many similarities with atopic dermatitis in human patients including
      infiltrating CD4(+) T cells and eosinophils in the skin, increased number of
      eosinophils in the blood and increased serum IgE. Thus, the relB(- / -) mouse
      should be a useful model to study the pathogenesis of this common allergic human
      disease.

PMID- 10940924
TI  - Characterization of MHC class II-presented peptides generated from an antigen
      targeted to different endocytic compartments.
AB  - We evaluated the capacity of the secretory pathway or of different endocytic
      compartments in B cell lines to generate MHC class II-presented peptides from the
      antigen ovalbumin (OVA). Sorting signals from the transferrin receptor (TFR),
      targeted a chimeric OVA fusion protein to early endosomes and led to the
      generation of 8 of 12 presented peptides. Sorting signals from the lysosome
      associated membrane protein 1 (LAMP-1), targeted an OVA fusion protein to
      lysosomes, and led to the generation of 9 of 12 peptides. In contrast, OVA with
      only a signal sequence led to the generation of only 2 presented peptides. There
      were both qualitative and quantitative differences in the generation of peptides
      from the different fusion proteins, suggesting that multiple distinct
      compartments are involved in generating different epitopes. One peptide was
      presented better from the TFR fusion protein, while all others were presented
      better from the LAMP-1 construct. Twelve peptides were generated from exogenously
      supplied OVA, including 3 peptides that were not generated from any of the fusion
      proteins. Since most endogenously synthesized foreign antigens are rarely
      presented on class II molecules, these studies further suggest a strategy whereby
      antigens in DNA-based vaccines could be targeted to endocytic compartments to
      enhance immunogenicity.

PMID- 10940925
TI  - Glucocorticoids drive human CD8(+) T cell differentiation towards a phenotype
      with high IL-10 and reduced IL-4, IL-5 and IL-13 production.
AB  - Glucocorticoids are highly effective in the treatment of allergy and asthma and
      inhibit the synthesis of IL-4, IL-5 and IL-13 by disease-promoting CD4(+) Th2
      cells. CD8(+) T cells also synthesize these cytokines, and the aim of this study
      was to investigate how glucocorticoids effect cytokine production by these cells.
      When CD8(+) T cells are stimulated with anti-CD3 and IL-2 plus IL-4 or
      dexamethasone, production of the anti-inflammatory cytokine IL-10 is low in both
      primary and secondary cultures restimulated with anti-CD3 and IL-2 alone.
      However, when both are present, a synergistic effect on IL-10 synthesis is
      observed. The additional presence of antigen-presenting cells (APC) in the
      priming culture maintains IL-10 levels, but inhibits IL-4 and IL-5 production.
      CD4(+) T cells develop a similar glucocorticoid-induced phenotype. These cells
      demonstrate regulatory activity and inhibit CD4(+) T cell activation in an IL-10
      dependent manner. Earlier reports show glucocorticoids promote a Th2 phenotype by
      effects on purified naive T cells or pretreatment of APC. This study
      demonstrates, more critically, that when APC are present, glucocorticoids induce
      CD4 and CD8 T cell populations synthesizing high levels of IL-10, but greatly
      reduced amounts of disease-promoting IL-4 and IL-5.

PMID- 10940926
TI  - Mast cells migrate, but do not degranulate, in response to fractalkine, a
      membrane-bound chemokine expressed constitutively in diverse cells of the skin.
AB  - Mast cells (MC) are anatomically located near nerves and blood vessels in skin
      and the gastrointestinal tract and tend to localize within certain cutaneous
      tumors such as neurofibromas. However, the molecular mechanisms by which MC home
      to these sites are not well characterized. Fractalkine (FK) is a membrane-bound
      CX3C chemokine that displays constitutive expression in dendritic cells as well
      as in non-hematopoietic tissues including mammalian brain. Here we show that FK
      is constitutively expressed by skin endothelial cells, dermal dendrocytes and
      cells within neurofibromas. By reverse transcription-PCR, FK receptor, CX3CR1, is
      expressed by cultured murine bone marrow-derived MC (BMMC) of both connective
      tissue and mucosal phenotypes. Non-activated human dermal MC isolated from
      neonatal foreskin similarly demonstrated CX3CR1 expression. In chemotaxis assays,
      FK attracted MC with maximal migration occurring between 25 - 125 ng / ml. BMMC
      were not stimulated to release proinflammatory mediators in the presence of FK as
      measured by granule-associated beta-hexosaminidase release. Thus, CX3CR1 is
      expressed by MC and effectively mediates chemotaxis without inducing
      degranulation. We propose that the constitutive expression of FK on certain cells
      in the skin may be a factor in the tissue-specific homing of MC.

PMID- 10940927
TI  - E/P-selectin-deficient mice: an optimal mutation for abrogating antigen but not
      tumor necrosis factor-alpha-induced immune responses.
AB  - Leukocyte recruitment in cremaster microcirculation was visualized by intravital
      microscopy, either in ovalbumin sensitized and challenged animals, or in response
      to TNF-alpha. In antigen-challenged mice a significant increase in leukocyte
      rolling (approximately 50 to 200-300 cells/min) and adhesion (2 to 15-20
      cells/100 microm), and a very dramatic increase in emigration ( approximately 1
      to >40 cells/field) was observed over 24 h. Although rolling and adhesion was
      dramatically blunted in P-selectin- or P selectin/ICAM-1-deficient mice,
      emigrated cell number was similar to that observed in wild-type mice. Leukocyte
      rolling, adhesion and emigration was almost entirely abrogated over 24 h in E/P
      selectin-deficient mice, demonstrating that antigen-induced leukocyte recruitment
      can be entirely disrupted in the absence of both endothelial selectins. However,
      E/P-selectin-deficient mice were able to recruit leukocytes at 24 h after TNF
      alpha challenge. Rolling 24 h post-TNF-alpha in E/P-selectin-deficient mice was
      not inhibitable with anti-L-selectin antibody, suggesting an entirely selectin
      independent pathway of rolling. We identified this pathway to be alpha (4)
      integrin dependent and demonstrated that VCAM-1 expression was increased only in
      mice challenged with TNF-alpha. These data demonstrate that, in vivo, sufficient
      amounts of TNF-alpha can recruit leukocytes independently of selectins, whereas
      inhibition of endothelial selectins is the optimal intervention in reducing the
      immune response to antigen.

PMID- 10940928
TI  - Leukocyte recruitment during onset of experimental allergic encephalomyelitis is
      CCR1 dependent.
AB  - We have shown that macrophages and microglia present within demyelinating plaques
      of patients with multiple sclerosis (MS) are immunoreactive for the chemokine
      receptor CCR1 and its ligand, macrophage inflammatory protein-1alpha. To test the
      importance of CCR1 to the pathogenesis of MS, we studied the progression of
      experimental allergic encephalomyelitis (EAE) in CCR1(+/+) vs. CCR1(-/-) mice.
      After immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide,
      nearly all CCR1(+/+) mice developed EAE (95% incidence, severity 2.5+/-0.1),
      whereas CCR1(-/-) mice had less severe disease (55% incidence, p<0.001; severity
      1. 2+/-0.2, p<0.001). CCR1(+/+) mice showed elevated brain mRNA for the
      chemokines immune protein (IP)-10, RANTES and monocyte chemoattractant protein-1
      prior to disease onset, whereas only IP-10 mRNA was elevated in CCR1(-/-) mice.
      Both groups of mice had comparable in vitro lymphocyte proliferation and cytokine
      production upon stimulation with MOG peptide, and similar cutaneous
      hypersensitivity responses to 2,4-dinitrofluorobenzene, suggesting that CCR1(-/-)
      mice were not systemically immunosuppressed. These data demonstrate that deletion
      of a chemokine receptor is at least partially protective in EAE, and suggest that
      targeting of CCR1 may be of therapeutic significance clinically.

PMID- 10940929
TI  - Engagement of the T lymphocyte antigen receptor regulates association of son-of
      sevenless homologues with the SH3 domain of phospholipase Cgamma1.
AB  - One mechanism for transducing signals downstream of lymphocyte receptor
      activation involves the stable association between signaling proteins. To
      identify protein ligands of the signal activator phospholipase Cgamma1
      (PLCgamma1), we screened T cell cDNA libraries with the PLCgamma1-SH3 domain by
      the yeast two-hybrid assay. We observed association between the PLCgamma1-SH3
      domain and the human Ras guanine nucleotide exchange factor son-of-sevenless-2
      (hSos2) through a proline-rich domain interaction. Stable and abundant hSos2 /
      PLCgamma1 and hSos1 / PLCgamma1 complexes were observed in unstimulated T cells.
      The interaction between these enzymes was augmented following engagement of the T
      cell antigen receptor (TCR / CD3). The kinetics of protein complex enhancement
      correlated with TCR / CD3-induced tyrosine phosphorylation of PLCgamma1; however,
      those PLCgamma1 molecules in complex with hSos2 were non-phosphorylated after TCR
      / CD3 stimulation, in contrast to the phosphorylated PLCgamma1 associated with
      the linker for activation of T cells, LAT. The Grb2 adapter protein was detected
      in complex with hSos / PLCgamma1, suggesting a regulatory role for Grb2. SH3
      domains from both Grb2 and PLCgamma1, but not RasGAP, bound directly to hSos
      homologues. The SH2 domain from Grb2 formed an association with the hSos /
      PLCgamma1 complex, which was enhanced following TCR / CD3 ligation. Together, the
      data suggest a mechanism for the son-of-sevenless and PLCgamma1 signal
      transducing enzymes in recruitment to protein complexes with potentially
      differential signaling consequences in T lymphocytes.

PMID- 10940930
TI  - An allotype-associated polymorphism in the gamma3 promoter determines the germ
      line gamma3 transcriptional rate but does not influence switching and subsequent
      IgG3 production.
AB  - The human IgG3 (b) allotype is associated with a high and the (g) allotype with a
      low mean serum level of IgG3 which is due to a low frequency of B cell switching
      in the latter. In the present study, we found a polymorphism in position -73 (C -
      > A), located in the 4th NF-kappaB site of the germ-line (GL) gamma3 promoter,
      resulting in a significant decrease of both the basal and induced activity in the
      (g) allotype-associated promoter. Over-expression experiments also showed that
      this polymorphism reduced the synergistic activation of the promoter by Stat6 +
      NF-kappaB p50 / p65 or Stat6 + C / EBPgamma. A low level of GL gamma3 transcripts
      was also observed in individuals carrying the (g) allotype-associated promoter
      region. However, an individual homozygous for a crossover between the promoter
      and switch region, i. e. with a (g) allotype-associated promoter and a (b)
      allotype-associated switch region, showed a normal level of switching and IgG3
      serum level. This suggests that although the (g) allotype-associated promoter is
      functionally inferior to that of the (b) allotype-associated promoter, these
      differences do not affect switching and final production of IgG3 and that
      polymorphisms in the switch region are more important in controlling this
      process.

PMID- 10940931
TI  - Cholera toxin induces maturation of human dendritic cells and licences them for
      Th2 priming.
AB  - Cholera toxin (CT) is a potent mucosal adjuvant that amplifies B and T cell
      responses to mucosally co-administered antigens, stimulating predominant Th2-type
      responses. However, little is known about the mechanism of adjuvanticity of CT
      and on the influence this toxin may have on Th2 cell development during the
      priming of an immune response. We analyzed the effect of CT on dendritic cells
      (DC), which are responsible for the priming of immune responses at the systemic
      as well as at the mucosal level. We found that CT induces phenotypic and
      functional maturation of blood monocyte-derived DC. Indeed, CT-treated DC up
      regulate expression of HLA-DR molecules, B7. 1 and B7.2 co-stimulatory molecules,
      and are able to prime naive CD4(+)CD45RA(+) T cells in vitro, driving their
      polarization towards the Th2 phenotype. Furthermore, CT-matured DC express
      functional chemokine receptors CCR7 and CXCR4 which may render them responsive to
      migratory stimuli towards secondary lymphoid organs. Interestingly, the
      maturation program induced by CT is unique since CT does not induce but rather
      inhibits cytokine (IL-12p70 and TNF-alpha) and chemokine (RANTES, MIP-1alpha and
      MIP-1beta) secretion by lipopolysaccharide- or CD40 ligand-activated DC. Our
      results help to elucidate the mechanism of action of CT as an adjuvant and
      highlight a new stimulus of bacterial origin that promotes maturation of DC.

PMID- 10940932
TI  - Specific antibody production by V(H)-gene replacement.
AB  - V(H)-gene replacement is a recombination event in which a pre-existing
      immunoglobulin heavy chain gene can be altered by the replacement of the
      rearranged V(H) gene segment with another V(H) gene segment. Although this event
      has been demonstrated in various model systems, its role in generating antibody
      diversity is still unsettled. We have used a genetically modified mouse strain,
      QM, with a quasi monoclonal primary B cell repertoire specific for NP to
      determine whether V(H) gene replacement can generate a new antigen specificity.
      Hybridomas generated from QM splenocytes after immunization with different
      antigens, gave rise to antibodies with specificity to the immunizing antigen or
      with new specificities. We found V(H)-gene replacement was used to change the
      original heavy chain gene rearrangement specific for NP into a heavy chain gene
      encoding the new antigen specificity. V(H)-gene replacement intermediates were
      detected both before and after the immunization, suggesting that the event was
      selective rather than instructive. These results demonstrate that V(H)-gene
      replacement can generate a new antibody heavy chain gene with a different
      functional and selectable antigen specificity.

PMID- 10940933
TI  - Subcellular localization of intracellular protein tyrosine phosphatases in T
      cells.
AB  - A high protein tyrosine phosphatase (PTPase) activity is required to maintain
      circulating T lymphocytes in a resting phenotype, and to limit the initiation of
      T cell activation. We report that 15 of the currently known 24 intracellular
      PTPases are expressed in T cells, namely HePTP, TCPTP, SHP1, SHP2, PEP, PTP-PEST,
      PTP-MEG2, PTEN, PTPH1, PTP-MEG1, PTP36, PTP-BAS, LMPTP, PRL-1 and OV-1. Most were
      found in the cytosol and many were enriched at the plasma membrane. Only TCPTP
      and PTP-MEG2 had subcellular localizations that essentially excludes them from a
      direct role in early T cell antigen receptor signaling events. Overexpression of
      6 of the PTPases reduced IL-2 gene activation, 3 of them thereby identified as
      novel candidates for negative regulators of TCR signaling. Our findings expand
      the repertoire of PTPases that should be considered for a regulatory role in T
      cell activation.

PMID- 10940934
TI  - The enhanced antigen-specific production of cytokines induced by pertussis toxin
      is due to clonal expansion of T cells and not to altered effector functions of
      long-term memory cells.
AB  - Pertussis toxin (PT) has been shown to act as an adjuvant that enhances the
      production of both Th1 and Th2 cytokines to coinjected protein antigens. It has
      remained unresolved, however, how PT affects the clonal sizes, long-term effector
      functions, and Th1/Th2/Th0 differentiation of the T cell responses induced. We
      have studied the effects of PT on the development of the CD4(+) T cell response
      to a prototypic antigen, hen eggwhite lysozyme (HEL). HEL injection with
      incomplete Freund's adjuvant (IFA) resulted in an IFN-gamma(-)/IL-5(+) Th2 recall
      response. In comparison, co-administration of PT with HEL:IFA enhanced the
      frequencies of IL-5-producing T cells up to eightfold, and induced the
      differentiation of high frequencies of IFN-gamma-producing CD4(+) T cells. The
      results showed that the IFN-gamma and IL-5 produced, originated from clonally
      expanded Th1 and Th2, but not Th0 cells, and that the effector functions of long
      term memory cells were unaffected. Adoptive transfer experiments suggested that
      PT mediated these effects via activation of APC, not by acting on the T cells
      directly. The effects of PT on the developing T cell response required the
      presence of the holotoxin (A- and B-subunit); the individual subunits did not
      show adjuvant effects. The data suggest that PT enhanced cytokine production by
      promoting differentiation and vigorous clonal expansion of Th1 and Th2 cells via
      activation of APC.

PMID- 10940935
TI  - Requirement for integration of phorbol 12-myristate 13-acetate and calcium
      pathways is preserved in the transactivation domain of NFAT1.
AB  - The transcription factor NFAT integrates signals from both calcium- and phorbol
      ester-stimulated signaling pathways. The calcium signal activates the calmodulin
      (CaM)-dependent phosphatase calcineurin, which dephosphorylates the regulatory
      domain of NFAT and promotes its nuclear import, while the phorbol ester signal
      results in synthesis and activation of Fos and Jun, transcription factors that
      bind cooperatively with the NFAT DNA-binding domain in the nucleus to mediate the
      transcription of many target genes. Here we show that transactivation by a GAL4
      fusion protein containing the strong acidic N-terminal transactivation domain
      (TAD) of NFAT1 also requires both calcium and phorbol ester stimulation. The
      calcium requirement can be mimicked by coexpression of activated versions of two
      CaM-dependent enzymes, calcineurin and CaM kinase IV. Our data indicate that a
      144-amino acid segment of NFAT1, containing the N-terminal TAD but lacking the
      DNA-binding and Fos/Jun interaction domains, resembles the full-length protein in
      requiring a combined input from two separate signaling pathways for optimal
      function in cells.

PMID- 10940936
TI  - Regulation of CD27 expression in the course of germinal center B cell
      differentiation: the pivotal role of IL-10.
AB  - The molecules of the TNF superfamily and their receptors play crucial roles in
      the humoral immune response. In view of the powerful effects on germinal center
      (GC) B cell differentiation, the expression of these molecules should be tightly
      regulated. In this study, we have undertaken a detailed analysis of the
      regulation of CD27 expression following the differentiation of GC B cells
      supported by a follicular dendritic cell line. We show that CD27 is
      differentially expressed on B cell subpopulations at different stages of
      differentiation. Naive B cells are virtually negative but plasma cells generated
      in vivo are strongly positive for CD27 expression. GC B cells that exhibit a
      moderate expression of CD27 remarkably up-regulate the expression levels of this
      molecule when they differentiate into plasma cells, which is induced by IL-10.
      The up-regulation of CD27 expression correlates with that of CD38. Therefore,
      high expression of CD27 molecules emerges as a specific marker for plasma cells.
      Our results suggest an important role for CD27 in the differentiation of GC B
      cells into plasma cells. Evaluation of CD27 expression levels may be of a
      clinical significance in assessment of B cell maturation in immunocompromised
      patients.

PMID- 10940937
TI  - Immunocytochemical localization of pedal peptide in the central nervous system of
      the gastropod mollusc Tritonia diomedea.
AB  - Tritonia pedal ganglion peptides (TPeps) are a trio of pentadecapeptides isolated
      from the brain of the nudibranch Tritonia diomedea. TPeps have been shown both to
      increase the beating rate of ciliated cells of Tritonia and to accelerate heart
      contractions in the mollusc Clione limacina. Here we examine the
      immunocytochemical distribution of TPeps in the Tritonia central nervous system.
      We found the brain and buccal ganglia to be rich sources of TPep
      immunoreactivity. Specific cells in both structures, some of them previously
      identified, were immunoreactive. Moreover, immunoreactive fibers were seen
      connecting ganglia and exiting almost all the major nerves. In the brain, we
      found that the paired, ciliated statocysts apparently receive TPep innervation.
      In addition, we observed unstained cell bodies in each buccal ganglion with
      extensive TPep immunoreactive projections surrounding their somata and primary
      neurites. Similar projections were not observed in the brain. We also compared
      the TPep immunoreactivity with that of SCP(b) in the buccal ganglia. We observed
      many neurons and processes that were immunoreactive to both peptides. One neuron
      that contains both TPep- and SCP(b)-like peptides (B12) has an identified role in
      the Tritonia feeding network. Together, these findings suggest that TPeps may
      play an active role in the central nervous system of Tritonia as
      neurotransmitters modulating orientation, swimming, and feeding.

PMID- 10940938
TI  - Ultrastructural evidence for a preferential elimination of glutamate
      immunoreactive synaptic terminals from spinal motoneurons after intramedullary
      axotomy.
AB  - After axotomy in the ventral funiculus of the cat spinal cord, about half of the
      population of lesioned motoneurons die at 1-3 weeks postoperatively, whereas the
      other half survives and generates new axons through the lesion area. To identify
      conditions that may promote survival and regeneration of motoneurons subjected to
      this kind of injury, the authors examined ultrastructurally lesion-induced
      changes in the number and distribution of nerve terminals on the somata and
      proximal dendrites of alpha-motoneurons in the 7th lumbar spinal segment (L7) of
      the cat spinal cord. Intramedullary axotomy resulted in a profound reduction in
      the number of nerve terminals impinging on the somata and proximal dendrites,
      with the maximal effect seen at 3 weeks postlesion. At that time, only 12-25% of
      the normal number of terminals remained on the cell somata, and 22-33% remained
      on proximal dendrites. Thereafter, a gradual increase in terminal numbers
      occurred, reaching normal levels at 34 weeks after the lesion. Already at 2 days
      postoperatively and, most obviously, at 3 weeks postoperatively, type S nerve
      terminals were eliminated to a larger degree than type F terminals. Postembedding
      immunohistochemistry confirmed that the largest reduction at 3 weeks was seen for
      excitatory glutamate-immunopositive type S nerve terminals (90%), whereas
      inhibitory glycine-immunoreactive and gamma-aminobutyric acid (GABA)
      immunoreactive type F terminals were affected less (70% reduction). This led to a
      distinct shift in the ratio between the numbers of terminals that were
      immunopositive for glycine and GABA and the numbers of terminals that were
      labeled for glutamate. For the cell body, this ratio increased from 3.7 in normal
      material to 14.5 in lesioned motoneurons, whereas the corresponding values for
      proximal dendrites were 3.8 and 7.5. The preferential elimination of
      glutamatergic inputs to lesioned motoneurons may reflect an active reorganization
      of the synaptic input to diminish the excitotoxic influence on these neurons,
      thereby promoting the survival of motoneurons after intramedullary axotomy.

PMID- 10940939
TI  - Intrinsic choroidal neurons in the duck eye express galanin.
AB  - Recently, it has been shown that the choroid of the duck eye harbours
      approximately 1,000 intrinsic choroidal neurons positive for vasoactive
      intestinal polypeptide and neuronal nitric oxide synthase. Their connections and
      functional significance are largely unknown. This study was performed to
      establish a typical chemical code for these neurons and to define their targets
      by using immunocytochemistry and confocal laser scanning microscopy. Almost all
      intrinsic choroidal neurons coexpressed galanin (GAL), vasoactive intestinal
      polypeptide (VIP), and neuronal nitric oxide synthase (nNOS)/NADPH-diaphorase. A
      few stained for GAL and/or nNOS only. Among extrinsic ganglia, GAL/VIP/nNOS
      coexpressing neurons were only found in the pterygopalatine ganglion where they
      accounted for approximately 30% of the neuronal population. Thus, GAL/VIP/nNOS
      positive nerve fibres around branches of the ciliary artery and within the
      nonvascular smooth muscle stroma of the choroid may originate mainly from
      intrinsic neurons and to some extent in a subpopulation of pterygopalatine
      ganglionic neurons exhibiting the same chemical coding. Close contacts of GAL
      positive fibres upon intrinsic choroidal neurons may indicate reciprocal
      connections between them. Thus, intrinsic choroidal neurons may represent
      peripherally displaced pterygopalatine ganglion neurons forming a local network
      for regulation of vascular and nonvascular smooth muscle tone in the duck
      choroid. They may be integrated in the neuronal circuitry controlling intraocular
      pressure, choroidal thickness, accommodation, and axial bulbus length.

PMID- 10940940
TI  - Central projections of Drosophila sensory neurons in the transition from embryo
      to larva.
AB  - Sensory axons of different sensory modalities project into typical domains within
      insect ganglia. Tactile and gustatory axons project into a ventral layer of
      neuropil and proprioceptive afferents, including chordotonal axons, into an
      intermediate or dorsal layer. Here, we describe the central projections of
      sensory neurons in the first instar Drosophila larva, relating them to the
      projection of the same sensory afferents in the embryo and to sensory afferents
      of similar type in other insects. Several neurons show marked morphologic changes
      in their axon terminals in the transition between the embryo and larva. During a
      short morphogenetic period late in embryogenesis, the axon terminals of the
      dorsal bipolar dendrite stretch receptor change their shape and their
      distribution within the neuromere. In the larva, external sense organ neurons
      (es) project their axons into a ventral layer of neuropil. Chordotonal sensory
      neurons (ch) project into a slightly more dorsal region that is comparable to
      their projection in adults. The multiple dendrite (md) neurons show two
      distinctive classes of projection. One group of md neurons projects into the
      ventral-most neuropil region, the same region into which es neurons project.
      Members of this group are related by lineage to es neurons or share a requirement
      for expression of the same proneural gene during development. Other md neurons
      project into a more dorsal region. Sensory receptors projecting into dorsal
      neuropil possibly provide proprioceptive feedback from the periphery to central
      motorneurons and are candidates for future genetic and cellular analysis of
      simple neural circuitry.

PMID- 10940941
TI  - Immunologic differentiation of two high-affinity neurotensin receptor isoforms in
      the developing rat brain.
AB  - Earlier studies have demonstrated overexpression of NT1 neurotensin receptors in
      rat brain during the first 2 weeks of life. To gain insight into this phenomenon,
      we investigated the identity and distribution of NT1 receptor proteins in the
      brain of 10-day-old rats by using two different NT1 antibodies: one (Abi3)
      directed against the third intracellular loop and the other (Abi4) against the C
      terminus of the receptor. Immunoblot experiments that used Abi3 revealed the
      presence of two differentially glycosylated forms of the NT1 receptor in
      developing rat brain: one migrating at 54 and the other at 52 kDa. Whereas the 54
      kDa form was expressed from birth to adulthood, the 52-kDa form was detected only
      at 10 and 15 days postnatal. Only the 52-kDa isoform was recognized by Abi4. By
      immunohistochemistry, both forms of the receptor were found to be predominantly
      expressed in cerebral cortex and dorsal hippocampus, in keeping with earlier
      radioligand binding and in situ hybridization data. However, whereas Abi4
      immunoreactivity was mainly concentrated within nerve cell bodies and extensively
      colocalized with the Golgi marker alpha-mannosidase II, Abi3 immunoreactivity was
      predominantly located along neuronal processes. These results suggest that the
      transitorily expressed 52-kDa protein corresponds to an immature, incompletely
      glycosylated and largely intracellular form of the NT1 receptor and that the 54
      kDa protein corresponds to a mature, fully glycosylated, and largely membrane
      associated form. They also indicate that antibodies directed against different
      sequences of G-protein-coupled receptors may yield isoform-specific
      immunohistochemical labeling patterns in mammalian brain. Finally, the selective
      expression of the short form of the NT1 receptor early in development suggests
      that it may play a specific role in the establishment of neuronal circuitry.

PMID- 10940942
TI  - Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ
      hybridization.
AB  - Nicotinic receptors are implicated in memory, learning, locomotor activity, and
      addiction. Identification of the specific receptor subtypes that mediate these
      behaviors is essential for understanding their role in central nervous system
      (CNS) function. Although expression of nicotinic receptor transcript has been
      studied in rodent brain, their localization in the monkey CNS, which may be a
      better model for the human brain, is not yet known. We therefore investigated the
      distribution of alpha4, alpha6, alpha7, beta2, beta3, and beta4 receptors subunit
      mRNAs in the monkey brain by using in situ hybridization. alpha4 and alpha7 mRNAs
      were very widely expressed, with a substantial degree of overlap in their
      distribution, except for the reticular nucleus of the thalamus in which alpha7
      mRNA was much more prominently expressed. beta2 and beta4 mRNA were also widely
      distributed, although beta4 was more prominently localized in thalamic nuclei
      than beta2. The distribution of alpha6 and beta3 mRNA was very distinct from that
      of the other transcripts, being restricted to catecholaminergic nuclei, the
      cerebellum, and a few other areas. Although there were similarities in
      distribution of the nicotinic receptor subunit mRNAs in monkey and rodent brain,
      there were prominent differences in areas such as the caudate, putamen, locus
      coeruleus, medial habenula, and cerebellum. In fact, the distribution of alpha4
      and alpha7 mRNAs in the monkey caudate and putamen was more similar to that
      reported in the human than rodent brain. These findings have implications for the
      development of drug therapies for neurological disorders, such as Alzheimer's and
      Parkinson's disease, in which nicotinic receptors are decreased.

PMID- 10940943
TI  - Crab stomach pyloric muscles display not only excitatory but inhibitory and
      neuromodulatory nerve terminals.
AB  - Movements of the foregut in crustaceans are produced by striated muscles that are
      innervated by motor neurons in the stomatogastric ganglion (STG). Firing of the
      STG motor neurons generates excitatory junctional potentials (EJPs) in the
      stomach muscles. We now provide evidence for the existence of separate inhibitory
      and neuromodulatory innervations of some pyloric muscles in the foregut of
      several crabs, Callinectes sapidus, Cancer magister, and Cancer borealis.
      Electron microscopic examination of several pyloric muscles revealed three
      distinct types of nerve terminals. Excitatory terminals were readily identified
      by the spherical shape of their small, clear synaptic vesicles. These terminals
      also housed a few large dense core vesicles. Inhibitory nerve terminals were
      recognized by the elliptical shape of their small, clear synaptic vesicles, and
      contacted the muscles at well-defined synapses equipped with dense bar active
      zones. Bath application of GABA reduced the amplitudes of EJPs in a pyloric
      muscle of C. borealis, consistent with the presence of GABAergic inhibitory
      innervation. Neuromodulatory terminals were characterized by their predominant
      population of large dense and dense core vesicles. These terminals formed
      synapses with presynaptic dense bars on the muscle, as well as on the excitatory
      and inhibitory nerve terminals. The presence of the inhibitory and
      neuromodulatory terminals creates a functional context for previously described
      reports of neuromodulatory actions on stomach muscles and suggests that the
      transfer function from STG motor patterns to pyloric movement may be orchestrated
      by a complex innervation from sources outside of the STG itself.

PMID- 10940944
TI  - Parallel somatotopic maps of gustatory and mechanosensory neurons in the central
      nervous system of an insect.
AB  - Relatively little is still known about the sense of taste, or contact
      chemoreception, compared with other sensory modalities, despite its importance to
      many aspects of animal behaviour. The central projections of the sensory neurons
      from bimodal contact chemoreceptors (basiconic sensilla) were compared with those
      from mechanosensory tactile hairs located on similar regions of the middle leg of
      the locust. Basiconic sensilla are multiply innervated, containing one
      mechanosensory and several chemosensory neurons, whereas tactile hairs are
      innervated by a single mechanosensory neuron. We show that the sensory neurons
      from tactile hairs form a complete 3-dimensional somatotopic map in the
      mesothoracic ganglion. Sensory neurons from hairs located on the coxa projected
      to a region near the midline of the ganglion with neurons from hairs located on
      progressively more distal parts of the leg arborizing in successively more
      lateral regions of neuropil. All the neurons from basiconic sensilla, both
      mechanosensory and chemosensory, also projected in a similar, strictly
      somatotopic, manner, and the arbors from these neurons overlapped considerably
      with those from tactile hairs on equivalent parts of the leg to form a continuous
      region. Thus, the position of a receptor on the leg is preserved in the central
      nervous system not only for the mechanosensory neurons from both tactile hairs
      and basiconic sensilla but also for chemosensory neurons. We could observe no
      anatomical features or small differences in projection region between sensory
      neurons from individual basiconic sensilla consistent with differences in
      modality.

PMID- 10940945
TI  - The normal distribution and projections of constitutive NADPH-d/NOS neurons in
      the brainstem vestibular complex of the rat.
AB  - The vestibular system is a highly conserved sensory system in vertebrates that is
      largely responsible for maintenance of one's orientation in space, posture, and
      balance and for visual fixation of objects during motion. In light of the
      considerable literature indicating an involvement of nitric oxide (NO) in sensory
      systems, it is important to determine whether NO is associated with vestibular
      pathways. To study the relationship of NO to vestibular pathways, we first
      examined the normal distribution of constitutive NADPH-diaphorase (NADPH-d), a
      marker for nitric oxide synthase (NOS), in the vestibular complex (VC) and then
      examined its association with selected vestibular projection neurons. Survey of
      the four major vestibular nuclei revealed that only the medial vestibular nucleus
      contained significant numbers of perikarya stained for NADPH-d/NOS. By contrast,
      all the vestibular nuclei contained a network of fine processes that stained
      positive for NADPH-d, although the density of this network varied among the
      individual nuclei. To determine whether NADPH-d/NOS neurons project to vestibular
      efferent targets, injections of the retrograde tracer Fluoro-Gold were made into
      known targets of second-order vestibular neurons. Vestibular neurons containing
      constitutive NADPH-d/NOS were found to project predominantly to the oculomotor
      nucleus. A small number of neurons also participate in vestibulothalamic and
      intrinsic vestibular connections. These results indicate that NADPH-d/NOS neurons
      are prevalent in the MVN and that a subpopulation of these neurons project to the
      oculomotor complex. Nitric oxide is probably released locally from axons located
      throughout the vestibular complex but may play a particularly important role in
      vestibulo-ocular pathways.

PMID- 10940946
TI  - Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP
      treated monkeys, and in Parkinson's disease patients.
AB  - The existence of a dopaminergic innervation of the subthalamic nucleus (STN) has
      been demonstrated in rats but has remained controversial in primates. The aim of
      the present study was first to demonstrate the existence of a dopaminergic
      innervation of the STN in monkeys using tracing methods and then to quantify the
      loss of dopaminergic fibers in the parkinsonian state in monkeys and humans.
      Following injection of Fluoro-Gold into the STN of a vervet monkey (Cercopithecus
      aethiops), retrogradely labeled neurons were found to be scattered in all
      dopaminergic areas of the mesencephalon. Injection of biotin dextran amine into
      dopaminergic areas A8 and A9 of two monkeys resulted in anterogradely labeled
      axons located throughout the whole extent of the STN. Labeled axons that also
      expressed tyrosine hydroxylase (TH) were reconstructed from serial sections. Some
      terminal axonal arborizations had profuse branching and occupied much of the STN,
      and others were restricted to small portions of the nucleus. In TH-immunoreactive
      sections, numerous sparse, fine, and varicose TH-positive fibers were observed in
      the STN of normal monkeys and humans. Quantification of these TH-positive fibers
      revealed a 51% loss of TH-positive fibers in MPTP-intoxicated monkeys and a 65%
      loss in Parkinson's disease patients compared with their respective controls.
      These findings demonstrate the existence of a dopaminergic innervation of the STN
      in primates. The loss of dopaminergic innervation in MPTP-intoxicated monkeys and
      in Parkinson's disease patients may directly affect the activity of STN neurons
      and could participate in the hyperactivity of the structure.

PMID- 10940947
TI  - Selective facilitation of the serotonin(1B) receptor causes disorganization of
      thalamic afferents and barrels in somatosensory cortex of rat.
AB  - Alteration of serotonin (5-HT) levels influences developing thalamocortical
      afferents (TCAs) in primary somatosensory cortex (SI) of rats and mice. The 5
      HT(1B) receptor, present on TCAs during the first postnatal week, may be involved
      in these effects. The present study asked whether administration of 5
      nonyloxytriptamine (NNT), a selective 5-HT(1B) receptor agonist, affects TCA
      organization in rat SI. Littermates were injected five times daily (5x/day), with
      either 0.1 mg/kg NNT or vehicle from birth to postnatal day 6 (P-6). Animals were
      killed on P-6, and their brains were processed for high-performance liquid
      chromatography (HPLC), cytochrome oxidase (CO) histochemistry, cresyl violet, or
      demonstration of TCAs by placement of 1,1'-dioctadecyl-3,3,3'' 3'-tetra
      methylindocarbocyanine perchlorate (Di-I) on thalamocortical radiations. At P-6,
      NNT treatment decreased 5-HT levels slightly compared with controls, although
      this difference was not statistically significant. In NNT-treated rats, the Di-I
      labeled vibrissae-related pattern showed a range of effects, from fusion of
      patches related to mystacial vibrissae in treated animals to a less distinct
      vibrissae-related pattern in SI barrelfield compared with controls. Staining for
      CO and Nissl stain in layer IV of SI showed a similar range of abnormalities.
      These results indicate that the agonist action of NNT at the 5-HT(1B) receptor
      causes TCA disorganization in rat barrel field cortex in the absence of elevated
      5-HT.

PMID- 10940948
TI  - Ultrastructural localization of gustducin immunoreactivity in microvilli of type
      II taste cells in the rat.
AB  - Gustducin is a transducin-like G protein (guanine nucleotide-binding protein)
      that is expressed in taste bud cells. Gustducin is believed to be involved in
      bitter and possibly sweet taste transduction. In the present study, we
      demonstrate that a subset of type II cells displays immunoreactivity to antisera
      directed against gustducin in taste buds of rat circumvallate papilla. Immunogold
      particles are present both in the microvilli and cytoplasm of the immunoreactive
      cells. Quantitative analysis of the data suggests that the number of colloidal
      gold particles (P<0.001) and nanogold particles (P<0.01) in the immunoreactive
      type II cells are much greater than in type I cells. There are also approximately
      2.5 times (P<0.05) as many colloidal gold particles associated with the
      microvilli versus the cytoplasm in the immunoreactive type II cells. The
      ultrastructural distribution of gustducin immunoreactivity is consistent with its
      proposed role in the initial events of sensory transduction by gustatory receptor
      cells.

PMID- 10940949
TI  - Sex differences, but no seasonal variations in the hippocampus of food-caching
      squirrels: a stereological study.
AB  - Recent studies have described sex differences in the relative size of the
      hippocampus that are associated with sex differences in space use in birds and
      short-lived mammals. A correlation between spatial learning and increased
      hippocampal volume has also been demonstrated in food-caching animals. Such
      results suggest that sexually dimorphic spatial learning (sex differences in
      space use during the breeding season) and seasonal variations in food-caching
      behavior (spatial memory for cache locations) might correlate with morphological
      changes in the hippocampus of adult long-lived mammals. We used modern
      stereological techniques to examine the volume and neuron number of the
      structures forming the hippocampal complex (dentate gyrus, CA3, and CA1) of wild
      adult eastern gray squirrels (Sciurus carolinensis) throughout the year. We
      observed differences in brain size between samples collected at different times
      of the year (October, January, and June). Our analysis showed sex differences,
      but no seasonal variations, in the volume of CA1 stratum oriens and stratum
      radiatum. There were no sex differences or seasonal variations in the relative
      volume or the number of neurons of any other layer of the structures forming the
      hippocampal complex. These results confirm the existence of sex differences in
      the structure of the hippocampus; however, this sexual dimorphism does not vary
      seasonally in adulthood and is likely to result from developmental processes.
      These results do not support the hypothesis that seasonal variations in food
      caching behavior might correlate with morphological changes, such as variations
      in volume or neuron number, in the hippocampal complex of adult long-lived
      mammals.

PMID- 10940950
TI  - The new genetics: opportunities for nursing research and leadership.

PMID- 10940951
TI  - Redefinition: coping with normal results from predictive gene testing for
      neurodegenerative disorders.
AB  - The purpose of this qualitative study was to describe the psychosocial impact and
      coping processes of normal (negative) results from predictive testing for an
      inherited neurodegenerative disease. Ten adults with normal results of predictive
      testing for the Huntington disease (HD) or the Pallido-Ponto-Nigral Degeneration
      (PPND) gene mutation participated in semi-structured interviews 1 month after
      receiving results, and seven of these participants were interviewed 6 months
      later. The major theme of Redefinition was derived using Knafl and Webster's
      analysis method (1988). People who received normal gene results experienced loss
      of former beliefs about themselves and developed new self definitions,
      relationships with family, and roles in society. This coping process evolved from
      a personal focus at 1 month to a broader future perspective at 6 months after
      testing. Identifying components of the redefinition process may be an important
      consideration in planning interventions to promote coping with normal gene
      results in persons within at-risk families.

PMID- 10940952
TI  - Impact of cardiopulmonary resuscitation training on perceived control in spouses
      of recovering cardiac patients.
AB  - The objectives of this study were to determine whether there are differences in
      emotional distress among spouses of recovering cardiac patients based on level of
      perceived control, and to determine whether perceived control can be enhanced by
      cardiopulmonary resuscitation (CPR) training. A total of 219 spouses of cardiac
      patients recovering from an acute cardiac event were enrolled and 196 completed
      the study. Spouses were assigned to either a no-treatment control group or one of
      two CPR training groups. Perceived control and emotional adjustment were measured
      at baseline and again 1 month after subjects received CPR training. Spouses with
      high perceived control were less anxious, less depressed, and less hostile at
      baseline. Perceived control increased significantly in spouses after both CPR
      training groups, but was unchanged in the control group. After a partner's
      cardiac event, perceived control is important for psychological recovery in
      spouses and can be increased by CPR training.

PMID- 10940953
TI  - Economic analysis of two models of low-risk maternity care: a freestanding birth
      center compared to traditional care.
AB  - Costs were compared for two models of maternity care for low-risk pregnant women:
      a freestanding birth center (FSBC) and a medical model of care (MC). Sixty-nine
      subjects were enrolled in the FSBC group and 77 in the MC. In the FSBC group,
      prenatal costs were higher (mean difference $751, p </=.001) and childbirth care
      was less expensive ($1472, p </=.01). When costs for the entire maternity care
      episode were summed, there were no differences between groups ($6087 vs. $6803).
      Sensitivity analysis demonstrated that the FSBC could be more cost-effective than
      MC if it increased its volume.

PMID- 10940954
TI  - Psychosocial factors as predictors of functional status at 1 year in patients
      with left ventricular dysfunction.
AB  - Chronic heart failure patients often experience significant functional
      impairments. A better understanding of the biopsychosocial correlates of
      functional status may lead to interventions that improve quality of life in this
      population. Social isolation, mood disturbance, low socioeconomic status, and non
      White ethnicity were evaluated as possible correlates of impaired functional
      status in 2,992 U.S. patients with left ventricular ejection fractions (LVEFs)
      </= 35%. Even after controlling for age and clinical characteristics, all of the
      psychosocial variables examined were significant predictors of risk for
      experiencing severe limitations in intermediate and social activities of daily
      living at 1 year, with adjusted odds ratios in the 1.5-2.0 range. The ability of
      psychosocial characteristics to predict future functional status was also
      independent of baseline functional status, comorbid medical conditions, and
      deterioration in heart failure signs and symptoms over the intervening year.
      These results suggest that psychosocial factors influence patient functional
      status even in the later phases of cardiac disease.

PMID- 10940955
TI  - Measuring imaging ability: psychometric testing of the imaging ability
      questionnaire.
AB  - Imaging ability, defined as the ability to create vivid mental images and to
      experience those images as if they were almost real, has been suggested as a
      moderator in effective use of guided imagery for symptom relief. Persons with
      good imaging ability are thought to be more likely to succeed in relieving a
      symptom with guided imagery than persons with poor imaging ability. The purpose
      of this paper is to describe the development of an instrument designed to measure
      imaging ability, the Imaging Ability Questionnaire (IAQ). A descriptive
      correlational design was used to conduct item analyses and explore psychometric
      properties of the IAQ. A total of 200 persons from the Midwest completed a 54
      item version of the IAQ. Twenty-two items that failed to discriminate among
      levels of imaging ability were eliminated from the questionnaire. The final
      version of the IAQ contained 32 items and demonstrated good internal consistency
      (alpha =.93) and test-retest reliability (r =.92). Support for construct validity
      of the questionnaire was provided by demonstrating expected differences in IAQ
      score between persons for whom imagery worked and persons for whom imagery did
      not work. Future testing and use of the questionnaire in research and practice
      are discussed.

PMID- 10940956
TI  - Measurement of preference for information in U.S. and Korean cardiac
      catheterization patients.
AB  - Seeking information is a common coping strategy of patients facing a stressful
      event. Persons differ, however, in how much information they want to help them in
      their coping process. Research-based practice related to patients' preferences
      for information is hampered by the lack of reliable, valid, and clinically useful
      instruments to measure preference for information. Furthermore, it is imperative
      that researchers and clinicians understand preference for information in
      different cultures to reflect the diversity of the needs of patients in clinical
      practice. This study was designed to determine the reliability and validity of
      three measures of preference for information-the Miller Behavioral Style Scale
      (MBSS), the Krantz Health Opinion Survey-Information Subscale (KHOS-I), and the
      Preference for Information Scale-in 106 U.S. and Korean cardiac catheterization
      subjects. The MBSS and the KHOS-I were found to have fair-to-excellent
      reliability and fair-to-moderate convergent validity. The lack of a correlation
      of either of these two instruments with the Preference for Information Scale does
      not support convergent validity for that instrument.

PMID- 10940957
TI  - Differences in the execution/nonexecution of advance directives by community
      dwelling adults.
AB  - Factors associated with the process of execution or nonexecution of advance
      directives, that is, living wills and/or durable powers of attorney for health
      care, by community dwelling adults are described. Data were collected by mail (n
      = 210, 51% response rate); 18.1% (n = 38) had executed an advance directive (AD).
      Significant differences were noted between AD executors and nonexecutors.
      Executors were older than nonexecutors. Executors had greater concern about an
      executed AD diminishing the quality of care they received. They participated in
      more MD-initiated discussions about ADs, and had more numerous AD educational
      experiences, more personal experience with the terminal illnesses or critical
      injuries of relatives or friends, a greater degree of familiarity with AD
      documents, and a greater degree of religiosity. The integration of these factors
      at various points along a continuum of intentional self-change moves an
      individual through several stages of a behavioral change process, culminating
      with the execution or nonexecution of an AD.

PMID- 10940958
TI  - Whatever happened to qualitative description?
AB  - The general view of descriptive research as a lower level form of inquiry has
      influenced some researchers conducting qualitative research to claim methods they
      are really not using and not to claim the method they are using: namely,
      qualitative description. Qualitative descriptive studies have as their goal a
      comprehensive summary of events in the everyday terms of those events.
      Researchers conducting qualitative descriptive studies stay close to their data
      and to the surface of words and events. Qualitative descriptive designs typically
      are an eclectic but reasonable combination of sampling, and data collection,
      analysis, and re-presentation techniques. Qualitative descriptive study is the
      method of choice when straight descriptions of phenomena are desired.

PMID- 10940960
TI  - Proceedings of the International Conference on Lead Exposure, Reproductive
      Toxicity, and Carcinogenicity. Gargnano, Italy, 7-9 June 1999.

PMID- 10940961
TI  - The reproductive toxicity and carcinogenicity of lead: a critical review.

PMID- 10940962
TI  - Lead poisoning in a historical perspective.
AB  - Lead poisoning existed and was already known in Antiquity but was forgotten, at
      least in the literature, until the end of the Middle Ages, where it was mentioned
      sporadically. In the 19th century this disease, which reached epidemic dimensions
      during the period of industrialization, was "rediscovered." Several comprehensive
      clinical articles appeared in the literature. The clinical picture deepened
      during the beginning of the 20th century, and preventive efforts were started.
      However, the concept of poisoning remained strictly clinical. During the latter
      half of the 20th century a new concept emerged: subclinical and early forms
      became recognized as undesirable effects. This led to a substantial lowering of
      hygienic standards. Pediatric poisoning has also been a serious problem during
      the 20th century. After the 1920s, environmental pollution by lead caused by the
      introduction of tetraethyl lead in gasoline became an alarming public health
      problem. The use became restricted in the 1980s; its effects on blood lead levels
      are now evident. Today's research focuses on the effects of low exposure, often
      with the aim of defining noneffect levels for different types of effects.

PMID- 10940963
TI  - Cancer mortality study of employees at lead battery plants and lead smelters,
      1947-1995.
AB  - BACKGROUND: This study has examined cancer mortality of a cohort of male U.S.
      workers exposed to lead. METHODS: The cohort consisted of 4,518 workers at lead
      battery plants and 2,300 at lead smelters. Vital status was ascertained between
      1947 and 1995. Site-specific cancer standardized mortality ratios (SMRs) and 95%
      confidence intervals (95% CIs), based on the mortality rates of the U.S. male
      population and adjusted for age and calendar time, were calculated for the total
      cohort as well as subcohorts stratified by various exposure parameters. In
      addition, a nested case-control study of stomach cancer (30 cases and 120 age
      matched controls) was also conducted. RESULTS: Mortality from all cancers was as
      expected (897 observed deaths, SMR = 103.8, 95% CI: 97.1-110.8). Mortality was
      significantly raised for stomach cancer (SMR = 147.4, 95% CI: 112. 5-189.8), lung
      cancer (SMR = 116.4, 95% CI: 103.9-129.9), and cancer of the thyroid and other
      endocrine glands (SMR = 308.0, 95% CI: 133. 0-606.8). There was a nonsignificant
      mortality deficit from kidney cancer (SMR = 63.6, 95% CI: 33.9-108.7). For
      bladder cancer, mortality was significantly lower than expected (SMR = 55.5, 95%
      CI: 31.7-90.1). Nonsignificant mortality deficits were also reported for cancer
      of the central nervous system (SMR = 74.8, 95% CI: 41.9-123. 4) and lymphatic and
      hematopoietic cancer (SMR = 92.2, 95% CI: 72. 4-115.7). Additional analyses by
      type of facility (lead battery plants vs. lead smelters), length of employment,
      latency, and period of hire were also performed. In the nested case-control study
      of stomach cancer, odds ratios were calculated for various exposure indices, and
      none was found to be elevated. Furthermore, no exposure-response relationship
      between lead exposure and stomach cancer was found in the nested case-control
      study. CONCLUSIONS: A significant mortality increase from stomach cancer was
      found. However, based on the analyses in the cohort study and the nested case
      control study, the increase did not appear to be related to lead exposure. A
      small, but statistically significant mortality increase from lung cancer was also
      observed. The small increase, in the absence of an exposure-response
      relationship, could be the result of confounding due to smoking, and was not
      likely causally related to lead exposure. Although the significant increase in
      cancer of the thyroid and other endocrine glands appeared to be consistent with
      an occupational interpretation, the small number of deaths (8), the lack of
      information on potential confounding factors, and the lack of reporting of a
      similar increase in other studies underscore the need to view this finding with
      caution. No increased mortality was found for kidney cancer, bladder cancer,
      cancer of the central nervous system, or lymphatic and hematopoietic cancer.

PMID- 10940964
TI  - Exposure of women in general populations to lead via food and air in East and
      Southeast Asia.
AB  - BACKGROUND: Despite increasing public concern of the possible health effects of
      lead (Pb) on general populations, reports on Pb levels in blood (Pb-B) and urine
      (Pb-B), as well as Pb intake via foods (Pb-F) for many Asian countries are
      scarce. The present study was initiated to elucidate the extent of non
      occupational Pb exposure among general populations in East and Southeast Asia.
      METHODS: In 1991-1997, peripheral blood, morning spot urine and 24-hour food
      duplicate samples were collected from 20 to 50 non-smoking adult women in each of
      four cities in Southeast Asia and five cities in Mainland China, and two cities
      each in Japan and Korea. The samples were wet-ashed and then analyzed by
      inductively coupled plasma mass spectrometry for Pb-B, Pb-U and Pb-F. Measures
      after logarithmic conversion were subjected to ANOVA and regression analysis.
      RESULTS: Geometric mean values in cities in East and Southeast Asia were in
      ranges of 32-65 microg/L for Pb-B, 2.1-7.5 microg/g cr for Pb-Ucr, and 7-32
      microg/day for Pb-F. The values for a combination of two cities of Tokyo and
      Kyoto, Japan (38 microg/L for Pb-B and 9.3 microg/day for Pb-F) appeared to be
      lower than the values for other Asian cities, and the values for all Japan (thus
      including both urban and rural areas) were even lower (19 microg/L for Pb-B and
      7.7 microg/day for Pb-F). Comparison of Pb uptake via respiratory and dietary
      routes showed that Pb via dietary route accounted for 15% of the total in Manila
      where Pb in air was high (ca. 650 ng/m(3)), whereas it was 54% in Tokyo+Kyoto
      where Pb in air was low (ca. 75 ng/m(3)). CONCLUSIONS: When compared
      internationally, Pb-F and Pb-B in Asia in general are similar to or somewhat
      higher than the levels in Europe and USA, whereas the levels in Japan are
      probably lower than the two latter areas. In Asia, Pb-F accounted for 15-54% of
      all Pb sources, the percentage being variable depending on local conditions
      especially Pb in atmospheric air.

PMID- 10940965
TI  - Environmental lead exposure in a population of children in northern France:
      factors affecting lead burden.
AB  - BACKGROUND: This study is part of the assessment of a site in northern France
      polluted by lead from industrial emissions. Our objectives were to look for the
      factors that influence lead burden in children aged 8-11 years. METHODS: A cross
      sectional population-based study took place in 1996-97 and included 400 children
      (200 of whom lived on the metal-polluted site). RESULTS: The geometric mean of
      the blood-lead levels of children living on the polluted site was 39.5 microg/l
      (95% CI = 36.3-43.1); that of the non-exposed children was 30.6 microg/l (95% CI
      = 27.8-33.6) (P < 0.0001). Analysis of the variations in the mean blood-lead
      levels showed associations with: distance from the smelting plants (mean blood
      lead level fell by a factor of 1/1.3 (95% CI = 1/1.2-1/1.4) for each km from the
      smelter over the range of 1-3 km and was constant thereafter) and consumption of
      tap water (when the water pipes were made of lead, the mean blood-lead level of
      children who drank tap water was twice as high (95% CI = 1.2-3.4) as that of
      children who did not). CONCLUSIONS: The children's blood-lead levels were
      essentially linked to two factors: proximity to the smelters and drinking tap
      rather than bottled water.

PMID- 10940966
TI  - Lead concentrations in elderly urban people related to blood pressure and mental
      performance: results from a population-based study.
AB  - BACKGROUND: The Kungsholmen project is a longitudinal study of ageing and
      dementia conducted in Stockholm in 1987. In a 1994-96 follow-up, 804 subjects had
      their blood samples analyzed for lead. METHODS: Lead concentration in blood in an
      elderly population aged 75+ (mean age of 88.4 years) was studied in relation to
      age, blood pressure (BP), body mass index (BMI), cognitive function measured with
      Mini-Mental State Examination (MMSE), gender, and smoking. RESULTS: The mean
      blood lead level (n = 762) was 3.7 microg/dL (0.18 micromol/L) whole blood with a
      standard deviation of 2.3, (0.11). There was a contribution of gender with men
      having higher blood lead levels than women (beta = -0.20; P = 0.000001) but not
      of smoking habits (beta = 0.07; P = 0.08) when these variables were entered into
      a multiple regression model with lead as the dependent variable (R = 0.22; P <
      0.000001). Different multiple regression models were tested with lead as the
      dependent variable. No relation was found between lead concentrations and age,
      BMI, systolic BP, diastolic BP, or MMSE. Systolic and diastolic BP were
      correlated to BMI (R = 0.10; P = 0.01 and R = 0.22; P = 0.000 001, respectively).
      CONCLUSIONS: In this elderly population from a specified area of Stockholm it is
      unlikely that lead exposure affects BP or cognition. However, high lead levels in
      blood may reflect earlier occupational exposure or life style factors.

PMID- 10940967
TI  - Lead and cancer in humans: where are we now?
AB  - BACKGROUND: Lead is only weakly mutagenic, but in vitro it inhibits DNA repair
      and acts synergistically with other mutagens. Lead acetate administered orally,
      cutaneously, or intraperitoneally causes kidney cancer, brain cancer (gliomas),
      and lung cancer in rodents, and acts synergistically with other carcinogens. Most
      cytogenetic studies of exposed workers have shown increases in chromosome
      aberrations or sister chromatid exchange, including some studies with positive
      exposure response trends. There are eight studies of cancer mortality or
      incidence among highly exposed workers; most are cohort studies of lead smelter
      or battery workers exposed decades ago. METHODS: We reviewed the epidemologic
      studies with regard to cancer. RESULTS: These studies provide some evidence of
      increased risk of lung cancer (RR = 1.30, 1.15-1.46, 675 observed deaths) and
      stomach cancer (combined RR = 1.34, 1.14-1.57, 181 observed). However, the lung
      cancer findings are not consistent across studies, and confounding by arsenic may
      affect the study with the highest lung cancer RR. Exclusion of that study yields
      a combined lung cancer RR of 1.14 (1.04-1.73). There is little evidence of
      increased risk of kidney cancer (combined RR = 1.01, 0. 72-1.42, 40 observed) or
      brain cancer (combined RR = 1.06, 0.81-1.40, 69 observed). However, two studies
      show a two-fold increase in kidney cancer, and one study shows a significant
      excess of gliomas. IARC classified lead as a "possible human carcinogen" based on
      sufficient animal data and insufficient human data in 1987. Six of the eight
      studies cited above have been published since 1987. CONCLUSIONS: Overall, there
      is only weak evidence associating lead with cancer; the most likely candidates
      are lung cancer, stomach cancer, and gliomas.

PMID- 10940968
TI  - The evidence that lead increases the risk for spontaneous abortion.
AB  - BACKGROUND: Reports from a period spanning more than a century, and covering
      occupationally exposed women in several countries, support an increase in
      pregnancy loss from high maternal lead exposures. Nevertheless, most studies
      conducted among populations with low/moderate exposures have provided little
      evidence of an association with pregnancy loss, or in particular, spontaneous
      abortions. METHODS: A critique of these low/moderate level studies reveals small
      sample sizes, problems in definition or ascertainment of outcome, lack of control
      for confounding, and/or deficiencies in the exposure assessment. For estimating
      exposure, either an ecologic measure was used, or individual biologic specimens
      were taken but attention was not paid to the timing of measurement of lead levels
      in these samples. A prospective study that overcame most of the deficiencies of
      previous studies enrolled pregnant women in Mexico City with low-to-moderate
      level lead exposures, collected blood specimens during their first trimester, and
      ascertained spontaneous abortions by week 20. A key design element of this study
      was the use of incidence-density-matched controls in order to achieve comparable
      opportunity for the outcome and comparable timing of exposure measurements. The
      latter is especially important because blood lead levels are altered by
      pregnancy. RESULTS: In the prospective Mexico City Study, a striking dose
      response relation between blood lead and risk of spontaneous abortion was found:
      the odds ratio for spontaneous abortion was 1.8 (95% confidence interval = 1.1
      3.1) for every 5 microg/dL increase in blood lead. CONCLUSIONS: Low-to-moderate
      lead exposures may increase the risk for spontaneous abortion at exposures
      comparable to U.S. general population levels during the 1970s and to many
      populations worldwide today; these are far lower than exposures encountered in
      some occupations. Further research is needed to confirm the association, to
      delineate the role of maternal vs. paternal exposures, and to assess increases in
      menstrual variability as an explanation for this finding.

PMID- 10940969
TI  - The effect of lead on male fertility: a time to pregnancy (TTP) study.
AB  - BACKGROUND: Growing attention has been paid in recent decades to the effects on
      male reproduction of occupational exposures to toxic agents. There is strong
      evidence that high level exposure to lead, i. e. blood lead level (PbB) > 70
      microg/dl, is associated with male infertility and some reports suggest an effect
      even at lower PbB (i. e. < 50 microg/dl). The aim of this study is to shed more
      light on the postulated association between occupational exposure to relatively
      low levels of inorganic lead and reduced fertility in men estimated by the length
      of time taken to conceive: time to pregnancy (TTP). METHODS: A survival analysis
      of TTP of the last pregnancy was performed adopting the Kaplan Meier methodology.
      The target population included 782 lead-exposed workers and 165 controls. 251
      lead workers and 119 controls were finally eligible and interviewed. Lead-exposed
      subjects were distributed into four exposure levels according to their blood lead
      concentration (i.e. < 20; 20-29; 30-39, and >/= 40 microg/dl). The Cox model was
      adopted to estimate the Relative Risk of unsuccessful waiting time to pregnancy
      associated to the exposure to lead. RESULTS: A statistically significant
      difference in fecundability (shorter TTP) in favor of exposed subjects was
      detected. Nevertheless, longer TTP was associated within the exposed group to
      higher levels of PbB, even though the gradient is not statistically significant.
      The exposed workers revealed an average number of children larger than those not
      exposed, and a clear gradient of the same variable was evident from the lowest to
      the highest PbB level. Focusing on subjects with one child only, the Cox model
      confirmed no significant difference in fecundability between exposed and not
      exposed, whereas a statistically significant longer TTP was associated to the
      exposure level >/= 40 microg/dl. CONCLUSIONS: It is not easy to assert or to deny
      the effect of inorganic lead on male fecundity, quantitatively estimated by TTP,
      with the data available for this study. In fact, while the general data seem to
      exclude effects of Pb on male fecundability a more detailed analysis suggests an
      unfavorable effect at relatively high levels of exposure but some confounding
      attributable to personal and social conditions of the workers cannot be ruled
      out. Further investigations with a better control of confounding are needed.

PMID- 10940970
TI  - Lead as a carcinogen: experimental evidence and mechanisms of action.
AB  - Recent epidemiological and experimental work confirms that inorganic lead
      compounds are associated with increased risks of tumorigenesis. In animals, these
      risks can be induced at doses that are not associated with organ toxicity and in
      mice that do not produce alpha-2 urinary globulin in the kidney. Thus the
      mechanisms of lead carcinogenicity are unlikely to be fully explained as toxicity
      related sequelae of high dose exposure or as a rat-specific response involving
      overexpression of a renal protein. Plausible mechanisms of lead carcinogenicity
      include direct DNA damage, clastogenicity, or inhibition of DNA synthesis or
      repair. Lead may also generate reactive oxygen species and cause oxidative damage
      to DNA. Recent data indicate that lead can substitute for zinc in several
      proteins that function as transcriptional regulators, including protamines. Lead
      further reduces the binding of these proteins to recognition elements in genomic
      DNA, which suggests an epigenetic involvement of lead in altered gene expression.
      These events may be of particular relevance in transplacental exposures and later
      cancer.

PMID- 10940971
TI  - Lead effects on protamine-DNA binding.
AB  - BACKGROUND: Lead impairs male fertility and may affect offspring of exposed
      males, but the mechanisms for this impairment are not completely clear. Protamine
      P1 and P2 families pack and protect mammalian sperm DNA. Human HP2 is a zinc
      protein and may have an important role in fertility. As lead has affinity for
      zinc-containing proteins, we evaluated its ability in vitro to bind to HP2 and
      its effects on HP2-DNA binding. Methods and Results UV/VIS spectroscopic data
      indicated that HP2 binds both Pb(2+) and Zn(2+)(as chloride salts). They also
      provided evidence that thiol groups mainly participate for Zn(2+)-binding;
      however, HP2 has additional binding sites for Pb(2+). The mobility shift assay
      showed that lead interaction with HP2 caused a dose-dependent decrease on HP2
      binding to DNA, suggesting that lead may alter chromatin stability. CONCLUSIONS:
      These in vitro results demonstrate that lead can interact with HP2 altering the
      DNA-protamine binding. This chemical interaction of lead with protamines may
      result in chromatin alterations, which in turn may lead to male fertility
      problems and eventually to DNA damage.

PMID- 10940972
TI  - DNA damage and repair in cells of lead exposed people.
AB  - BACKGROUND: One of the main sources of occupational exposure to lead in Colombia
      is in workers of battery industries and lead smelters. Genotoxic studies in human
      populations exposed to this metal have had conflicting results; this type of
      study has not been reported in Colombia. METHODS: Genotoxic effects of lead were
      studied in blood cell samples from workers of electric battery factories exposed
      to lead compounds. Single strand breaks and interference with DNA repair
      processes after an in vitro exposure of x-rays (300 cGy) were analyzed using the
      Comet Assay. The battery workers (n = 43) and 13 people not occupationally
      exposed to lead compounds who were selected as a control group, were classified
      into four categories according to their blood lead level. RESULTS: A significant
      difference was observed in DNA damage before the x-rays exposure (basal) between
      the lowest and highest categories of lead (mean DNA migration 55.6 micro and 85.9
      micro, respectively). Additionally, a significant difference in DNA migration was
      also found immediately after irradiation between the lowest and highest lead
      categories (mean DNA migration: 199.8 micro and 317.8 micro respectively). The
      DNA migrations at different times after irradiation did not show a significant
      difference among the different lead levels. CONCLUSIONS: We concluded that
      although the single strand breaks following irradiation were not affected by
      blood lead concentration, the metal seems to sensitize the cells to damage
      induced by other genotoxicants.

PMID- 10940973
TI  - Cloning genes whose levels of expression are altered by metals: implications for
      human health research.
AB  - When cells are exposed to toxicants, changes in gene expression ensue. To date,
      there is little information on gene expression changes induced by metals in
      mammalian cells. The basic methods for identifying altered gene expression of
      both a temporary and a permanent nature are outlined, with examples drawn mostly
      from what is known about metal-induced changes in gene expression. The
      application of this information in the development of new biomarkers of exposure
      and effect, in identifying individuals with altered susceptibility to metal
      compounds, and in the choice of genes for microarrays is discussed.

PMID- 10940974
TI  - Effects of four inorganic lead compounds on the proliferation and junctional
      coupling of cultured REL liver cells.
AB  - BACKGROUND: Chronic, low-level exposure to inorganic lead (Pb) has been involved
      in a number of human diseases, including tumors. In this study, the effect of
      four different inorganic Pb compounds (acetate, chloride, monoxide, and sulfate)
      was evaluated, in vitro, on liver-derived REL cells, known to be very sensitive
      to tumor promoters. METHODS: Cytotoxicity and effects on intercellular
      communication (GJIC) were evaluated, respectively, by cell- density/proliferation
      and dye-transfer assays. Pb concentration in the media solutions used for each
      treatment was quantified by atomic absorption spectroscopy-electrothermal
      atomization. RESULTS: Each of the Pb compounds we tested showed a typical dose-
      and time-related effect on REL cell proliferation, this effect not being related
      to the free metal concentration. Contrary to classical tumor promoters, none of
      the compounds significantly affected REL GJIC (1-hour treatment). CONCLUSIONS:
      Our results are indicative of specificity in the effects of the different Pb
      compounds. The mechanism(s) of their action need further investigations.

PMID- 10940975
TI  - Effects of lead on immune parameters in occupationally exposed workers.
AB  - BACKGROUND: To assess the immune competence of workers occupationally exposed to
      lead, several subsets of peripheral lymphocytes, i.e., T, TCD4(+), TCD8(+), B, NK
      cells, serum immunoglobulin and complement protein concentrations, chemotaxis,
      and intracellular killing activity of neutrophils of 25 male storage battery
      workers have been analyzed and compared to 25 healthy males with no history of
      lead exposure. RESULTS: The results of this study which indicated that industrial
      exposure to lead resulting in group mean blood lead concentrations of 75 +/- 18
      microg/dl are associated with a significant depression of: T helper lymphocytes,
      Ig G, Ig M and C3, C4 complement levels, chemotaxis, and random migration of
      neutrophils. No correlation was found between the duration of exposure and the
      altered immune parameters. CONCLUSIONS: The immune system can be a target for
      lead toxicity and elimination of lead hazard in working places is necessary.

PMID- 10940976
TI  - Relationship between delta-aminolevulinic acid dehydratase genotypes and heme
      precursors in lead workers.
AB  - BACKGROUND: The objective of this study was to investigate the relationships
      between genotypes of delta-aminolevulinic acid (ALA) dehydratase (ALAD) and
      disturbances in the heme biosynthetic pathway by lead exposure. METHODS: The
      subjects were 192 male lead workers and 125 control subjects. Blood lead
      concentrations (Pb-B), plasma ALA concentrations (ALA-P), and ALAD genotypes were
      determined for all subjects. In lead workers, ALAD activity, ALA in urine (ALA
      U), and erythrocyte zinc protoporphyrin (ZP) were also determined. RESULTS: The
      frequency of ALAD2 (minor type of ALAD allele) was calculated to be 0.087 in all
      subjects. No significant relationship was found between ALAD2 frequency and Pb-B
      levels in lead workers. ALAD1 homozygotes showed significantly higher levels of
      ZP and ALA-P in comparison with those of ALAD2 carriers at Pb-B levels more than
      20 microg/dL and 40 microg/dL, respectively. CONCLUSIONS: ALAD1 homozygotes might
      be more susceptible than ALAD2 carriers to disturbances in heme metabolism caused
      by lead exposure.

PMID- 10940977
TI  - One century of studies on lead poisoning in papers published in La Medicina del
      Lavoro.
AB  - One century of papers published in the Italian journal of occupational medicine,
      La Medicina del Lavoro, shows clearly that the study of lead is an exemplary
      topic for occupational physicians, enabling them to observe the evolution of
      research in the field of occupational health. The numerous pathological features
      of lead poisoning, doctors' successive therapeutic responses, and their gradual
      development of preventive techniques, form a paradigm that has subsequently been
      applied to all other fields of industrial toxicology. The evolution of the study
      of lead poisoning during this century is a complete example in the field of
      occupational toxicology for medical students: it will stimulate them in applying
      both clinical and preventive knowledge in the field of industrial toxicology.

PMID- 10940979
TI  - Strategies for the Design of Drugs Targeting RNA and RNA-Protein Complexes.
AB  - In many steps of gene replication and expression, RNA molecules participate as
      key players, which renders them attractive targets for therapeutic intervention.
      While the function of nucleic acids as carriers of genetic material is based on
      their sequence, a number of important RNAs are involved in processes that depend
      on the defined three-dimensional structures of these molecules. As for proteins,
      numerous complex folds of RNA exist. The development of drugs that bind
      specifically to RNA folds opens exciting new ways to expand greatly the existing
      repertoire of protein-targeted therapeutics. Most functions of RNAs involve
      interactions with proteins that contain RNA-binding domains. Effector molecules
      targeted at RNA may either alter the functional three-dimensional structure of
      the nucleic acid, so the interaction with proteins is thereby inhibited or
      enhanced, or, as interface inhibitors, they may directly prevent the formation of
      competent RNA-protein complexes. While the same tools used for the design of
      protein-targeted drugs may be considered for studying effectors binding to
      nucleic acids, the differences between proteins and RNAs in the forces which
      dominate their three-dimensional folding call for novel drug design strategies.
      In the present review, I will outline how our rapidly expanding knowledge of RNA
      three-dimensional structure and function facilitates rational approaches to
      develop RNA-binding compounds. Putative RNA targets for therapeutic intervention
      will be discussed along with recent advances in understanding RNA-small molecule
      and RNA-protein interactions.

PMID- 10940980
TI  - Gemini Surfactants.
AB  - How easy it is to dismiss the humdrum surfactant! After all, its structure is
      unglamorous by present-day norms. And the surfactant has been entrenched in so
      many areas of commerce for so many decades that its chemistry might seem old and
      tired. The purpose of this review is to persuade the reader otherwise, all the
      while focusing on a remarkable new surfactant, the gemini. Geminis, the common
      name for "bis-surfactants", can self-assemble at concentrations almost a
      hundredfold lower than for corresponding conventional surfactants. Surface
      activity can be improved a thousandfold. Geminis have already shown promise in
      skin care, antibacterial regimens, construction of high-porosity materials,
      analytical separations, and solubilization processes. Scores of patents dealing
      with geminis have appeared in the last few years. Indeed, geminis might well turn
      out, in the opinion of some, to be more useful to "l'homme de la rue" than crown
      ethers or fullerenes. This review delves into such topics as synthesis, critical
      micellization concentration, aggregate size and shape, gels, vesicles, and films.
      The information comes from scientists all over the world; one might say that
      gemini research is bathed in a continuous sunlight or summer. No prior knowledge
      of colloid chemistry is presupposed in this article.

PMID- 10940981
TI  - Syntheses of Functionalized and Aggregating Helical Conjugated Molecules I thank
      the US National Science Foundation for support (CHE98-02316).

PMID- 10940982
TI  - B-H Bond Activations in the Alkane Analogues H(3)B small middle dotPR(3).

PMID- 10940983
TI  - Redox-Induced "Zipper" Action in Rb(2)Bi(4)Se(7) and Cs(2)Bi(4)Se(7): Coupling of
      Slabs to a Three-Dimensional Framework through Single-Crystal to Single-Crystal
      Conversion Financial support from the Office of Naval Research (contract No.
      N00014-98-1-0443) is gratefully acknowledged. The work made use of the SEM
      facilities of the Center for Electron Optics at Michigan State University (MSU).
      The Siemens SMART CCD diffractometer at MSU was purchased with funds from the
      National Science Foundation (CHE-9634638). We thank Victor G. Young and the X-ray
      Crystallographic Laboratory of the University of Minnesota for collecting the
      data set of RbBi(4)Se(7).

PMID- 10940984
TI  - A Novel Method To Generate Chiral Quaternary Carbon Centers of High Enantiomeric
      Purity Using a Highly Stereoselective Addition of Vinylalanes to a Chiral
      Aldehyde We acknowledge the Natural Sciences and Engineering Council of Canada
      and Merck-Frosst for financial support.

PMID- 10940985
TI  - Exceptional Deshielding of (59)Co Caused by Deuteration of the Hydrogen Bonds in
      Cobaloximes This work was supported by MURST under the Project Cofin (MURST 97
      CFSIB).

PMID- 10940986
TI  - Enantiopure Simple Analogues of Annonaceous Acetogenins with Remarkable Selective
      Cytotoxicity towards Tumor Cell Lines This work was supported by the Chinese
      Academy of Sciences (nos. KJ951-A1-504-04, and KJ952-S1-503), the National
      Natural Science Foundation of China (nos. 29472070, 29790126, and 29832020), and
      the Ministry of Science and Technology of China (no. 970211006-6).

PMID- 10940987
TI  - Thermal Intermolecular Hetero Diels-Alder Cycloadditions of Aldehydes and Imines
      via o-Quinone Dimethides This work was supported by the National Institutes of
      Health (AI 16943/CA 28824). Postdoctoral Fellowship support is gratefully
      acknowledged by M.F.H. (5T32 CA62948-05) and J.G.A (NIH, CA-80356). We are
      grateful to Dr. George Sukenick (NMR Core Facility, Sloan-Kettering Institute)
      for NMR and mass spectral analyses.

PMID- 10940988
TI  - First Experimental Observation on Different Ionic States of both Methylthio
      (CH(3)S(.)) and Methoxy (CH(3)O(.)) Radicals This research was supported by the
      National Natural Science Foundation of China, Contract No. 29 673 049. M.F.G.
      gratefully acknowledges the support of the K. C. Wong Education Foundation, Hong
      Kong. X.J.Z., Z.S., and J.W. would like to thank the Chinese Academy of Sciences
      for receipt of scholarships over the period of this work.

PMID- 10940989
TI  - The Kinetic Order of an Interfacial Diels-Alder Reaction Depends on the
      Environment of the Immobilized Dienophile We are grateful for the support
      provided by the MRSEC (National Science Foundation, DMR-9808595) and DARPA.

PMID- 10940990
TI  - Highly Efficient Phosphapalladacyclic Catalysts for the Hydroarylation of
      Norbornene.

PMID- 10940991
TI  - Synthesis and X-ray Structures of

PMID- 10940992
TI  - Adrenaline Release by Chromaffin Cells: Constrained Swelling of the Vesicle
      Matrix Leads to Full Fusion At the ENS, this work has been supported in part by
      the CNRS (UMR 8640, Ultimatech and the program "Physique et Chimie du Vivant"),
      by the ENS, and by the French Ministry of Research and Education (MENESR). At the
      UNC, this work was supported by the NIH.

PMID- 10940993
TI  - Giant Artificial Ion Channels Formed by Self-Assembled, Cationic Rigid-Rod beta
      Barrels We thank Dr. E. Buck (Warner Instrument Corp., Hamden, CT) and R. Marclay
      (University of Geneva) for installation of a BLM workstation, Dr. E. Buck for BLM
      instructions, A. Pinto, J.-P. Saulnier, the group of Prof. Gulacar, and Dr. H.
      Eder for NMR, MS, and elemental analyses, respectively (University of Geneva),
      and the Swiss NSF and Suntory Institute for Bioorganic Research (SUNBOR Grant)
      for financial support.

PMID- 10940994
TI  - A Novel Catalytic System for the Mannich-Type Reaction of Silyl Enolates:
      Stereoselective Synthesis of beta-Aminoketones Studies on Organosilicon
      Chemistry, Part 148. This work was partly supported by Grants-in-Aid for
      Scientific Research, Grants-in-Aid for Scientific Research on Priority Areas No.
      706 (Dynamic Control of Stereochemistry) from the Ministry of Education, Science,
      Sports, and Culture, Japan, by Hitachi Chemical Industries, Inc., and by Pfizer
      Pharmaceuticals, Inc. Part 147: H. Ito, A. Hosomi, J. Syn. Org. Chem. Jpn. 2000,
      58, in press.

PMID- 10940995
TI  - An Unprecedented Hexapotassium-Hexamagnesium 24-Membered Macrocyclic Amide: A
      Polymetallic Cationic Host to Six Monodeprotonated Arene Anions This work was
      supported by the UK Engineering and Physical Science Research Council (Grant
      award No. GR/M78113). Thanks are also extended to Dr. P. J. Nichols for help with
      the crystallographic work.

PMID- 10940996
TI  - Low-Temperature Hydrogenolysis of Alkanes Catalyzed by a Silica-Supported
      Tantalum Hydride Complex, and Evidence for a Mechanistic Switch from Group IV to
      Group V Metal Surface Hydride Complexes We are grateful to Dr. L. Lefort, Dr. O.
      Maury (LCOMS), Dr. C. Meric de Bellefon, and Dr. D. Schweich from the laboratory
      LGPC (ESCPE Lyon) for fruitful discussions. We wish to thank the CNRS, and the
      ESCPE-Lyon for financial support. M.C. is also grateful to the French Ministry
      for Education, Research, and Technology (MENRT) for a predoctoral fellowship.

PMID- 10940997
TI  - Unprecedented Formation of Five-, Six-, and Seven-Membered Metallacycles by
      Single and Double Insertion of Mono- and Disubstituted Alkynes into an Rh-O Bond
      We thank Prof. Shigetoshi Takahashi and Dr. Fumie Takei at The Institute of
      Scientific and Industrial Research, Osaka University for the measurement of FAB
      mass spectra.

PMID- 10940998
TI  - A Grid Complex

PMID- 10940999
TI  - Intermolecular Trapping of the Nazarov Intermediate: Domino Electrocyclization/

PMID- 10941000
TI  - Reaction of

PMID- 10941001
TI  - Highly Regioselective Allylic Alkylation of Dienyl Acetates and Enynyl Acetates
      Catalyzed by an Iridium Complex This work was supported by a Grant-in-Aid for
      Scientific Research on Priority Areas (No. 283, "Innovative Synthetic Reactions")
      from the Ministry of Education, Science, Sports, and Culture, Government of
      Japan.

PMID- 10941002
TI  - Dipolar Dye Aggregates: A Problem for Nonlinear Optics, but a Chance for
      Supramolecular Chemistry This work was supported by the Deutsche
      Forschungsgemeinschaft (Wu 317/1), the Fonds der Chemischen Industrie and BASF AG
      (travel grant for S.Y.). We thank Dr. Udo Werz for 2D NMR experiments and Prof.
      Peter Bauerle for his support.

PMID- 10941003
TI  - Chiral 1,1'-Diphosphetanylferrocenes: New Ligands for Asymmetric Catalytic
      Hydrogenation of Itaconate Derivatives We would like to thank Dr. Daniela
      Herzberg for developing the procedure employing LDA as a base in the preparation
      of FerroTANE ligands. We also gratefully acknowledge analytical support of
      Catherine Rippe and Colin Dewar of Chirotech Technology Ltd.

PMID- 10941004
TI  - {K subset

PMID- 10941005
TI  - Gd(8)Se(15)-A 24-Fold Superstructure of the ZrSSi Type Financial support by the
      Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie is
      gratefully acknowledged; one of us (E.D.) is additionally indebted to the
      Deutscher Akademischer Austauschdienst for her grant.

PMID- 10941006
TI  - Hydrogen-Bonded Dioxygen Adduct of an Iron Porphyrin with an Alkanethiolate
      Ligand: An Elaborate Model of Cytochrome P450 This research was supported by the
      Ministry of Education, Science, and Culture, Japan (Grant-in Aids #08CE2005,
      09235225, and 11228207 to Y.N.) and through an Encouragement of Young Scientists
      stipendium (#08740500 to F.T.).

PMID- 10941007
TI  - Industrial Synthesis of (+)-cis-Methyl Dihydrojasmonate by Enantioselective
      Catalytic Hydrogenation; Identification of the Precatalyst

PMID- 10941008
TI  - Constant Selectivity Relationships of Addition Reactions of Carbanions We thank
      Dipl.-Chem. R. Loos for the investigation of 3 g and the Fonds der Chemischen
      Industrie for financial support.

PMID- 10941009
TI  - [PtIn]

PMID- 10941010
TI  - A Novel Bovine beta-1,4-Galactosyltransferase Reaction To Yield beta-D
      Galactopyranosyl-(1-3)-Linked Disaccharides from L-Sugars The authors are
      grateful for the funding of the Regional Leading Research Project of Shizuoka
      Prefecture from the Ministry of Science and Technology of the Japanese
      Government, and for funding from the Deutsche Forschungsgemeinschaft.

PMID- 10941011
TI  - Two-State Reactivity in the Rebound Step of Alkane Hydroxylation by Cytochrome P
      450: Origins of Free Radicals with Finite Lifetimes This research was sponsored
      by the Israeli Science Foundation (ISF) and, in part, by the German Israeli
      Foundation (GIF), and the VW Stiftung. S.S. thanks the Humboldt Foundation for a
      Senior Research Award. F.O. thanks the EU for a Marie Curie Fellowship.

PMID- 10941012
TI  - Redirecting Secondary Bonds To Control Molecular and Crystal Properties of an
      Iodosyl- and an Iodylbenzene This work was supported by the donors of The
      Petroleum Research Fund, administered by the American Chemical Society, and by
      the Ohio Board of Regents (for financial support of the Ohio Crystallographic
      Consortium).

PMID- 10941013
TI  - A General Entry into Glycopeptide "Dendrons" This work was financed by a grant
      for the glycobiotechnology program of the German Ministry of Eduction and Science
      (BMBF). We thank Dr. V. Sinnwell for the sophisticated NMR experiments and Dipl.
      Chem. M. Dubber for the MALDI-TOF measurements.

PMID- 10941014
TI  - Isolation of the Phenyl Cation in a Solid Argon Matrix This work was financially
      supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
      Industrie. M.W. thanks the Fonds der Chemischen Industrie for a stipend.

PMID- 10941016
TI  - The Tetracycline Repressor-A Paradigm for a Biological Switch.
AB  - The excessive use of antibiotics has enabled bacteria to develop resistance
      through a variety of mechanisms. The most common bacteriostatic action of the
      broad-spectrum antibiotic tetracycline (Tc) is by the inactivation of the
      bacterial ribosome so that the protein biosynthesis is interrupted and the
      bacteria die. The most common mechanism of resistance in gram-negative bacteria
      against Tc is associated with the membrane-intrinsic protein TetA, which exports
      invaded Tc out of the bacterial cell before it can attack its target, the
      ribosome. The expression of TetA is tightly regulated by the homodimeric Tet
      repressor (TetR)(2), which binds specifically with two helix-turn-helix motifs of
      operator DNA (tetO; K(ass) approximately 10(11) M(-1)) located upstream from the
      tetA gene on a plasmid or transposon. When Tc diffuses into the cell it chelates
      Mg(2+) and the complex [MgTc](+) binds to (TetR)(2) to form the induced complex
      (TetR small middle dot[MgTc](+))(2). This process is associated with
      conformational changes, which sharply reduce the affinity of (TetR)(2) to tetO,
      so that expression of TetA can take place, thus conferring resistance to the
      bacteria cells against Tc. Crystallographic studies show sequence-specific
      protein-nucleic acid interactions in the (TetR)(2) small middle dottetO complex
      and how the binding of two [MgTc](+) to (TetR)(2) enforces conformational changes
      that are stabilized by cooperative binding of two chains of eight water molecules
      each so that the formed (TetR small middle dot[MgTc](+))(2) is no longer able to
      recognize and bind to tetO. Since the switching mechanisms of the TetR/[MgTc](+)
      system is so tight, it has proven very useful in the regulation of eukaryotic
      gene expression and may also be applicable in gene therapy.

PMID- 10941017
TI  - Conformation Design of Open-Chain Compounds.
AB  - At the brink of the 21st century, chemistry is increasingly concerned with the
      function that molecules fulfil as drugs, receptors, or-as ensemble of molecules
      as materials. The capability of compounds to fulfil such functions cannot
      sufficiently be described by using only the terms composition and configuration.
      A decisive role is played in addition by the conformation of the molecules, which
      serves as the link between molecular composition and molecular function.
      Expressions such as "active conformation" or "competent conformation" allude to
      this aspect. Chemists have to develop an understanding how a flexible molecule
      adopts the conformation (a distinct shape) which is optimal for the function in
      question and how this process can be controlled. On the outset of such
      considerations, we may ask how nature succeeded in the process of evolution to
      endow flexible molecules with a preference to adopt the conformation which is
      optimal for the function it has to serve. In this review, I report on how we have
      reached a crude level of understanding of conformation design in nature with
      reference to the class of polyketide natural products, how we developed these
      insights into a conformation design of open-chain compounds, and which
      applications are already in sight.

PMID- 10941018
TI  - A Diborane Story I thank the Ava Helen and Linus Pauling Archive at Oregon State
      University in Corvallis, Oregon, and its director Clifford Mead for permission to
      quote from Pauling's correspondence, and Professor Roald Hoffmann for a useful
      discussion.

PMID- 10941019
TI  - Synthesis of Medium-Sized Rings by the Ring-Closing Metathesis Reaction.

PMID- 10941020
TI  - New Sulfur- and Selenium-Based Traceless Linkers-More than just Linkers?

PMID- 10941021
TI  - A New, Methane Adsorbent, Porous Coordination Polymer

PMID- 10941022
TI  - Structure and Mechanism in Cinchona Alkaloid Chemistry: Aqueous Hydrolysis
      Proceeds with Complete Inversion or Complete Retention of Configuration We thank
      Stefanie Roper for experimental contributions, Olaf Schrake for discussion,
      Ulrike Eggert and Lars Ole Haustedt for their help, Dr. Hofer for NMR analysis,
      and two referees for their critical comments. Our work was supported by the
      Friedrich-Naumann-Stiftung (PhD. Fellowship for W.M.B.), Chininfabrik Buchler
      GmbH (gift of Cinchona alkaloids) and the Fonds der Chemischen Industrie.

PMID- 10941023
TI  - P(6) Manganocene and P(3) Cymantrene: Consequences of the Inclusion of Phosphorus
      Atoms in Mn-Coordinated Cyclopentadienyl Ligands This work was supported by the
      Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. A.E.,
      M.H., and M.Z. thank the DFG-Graduiertenkolleg ("Phosphorchemie als Bindeglied
      verschiedener chemischer Disziplinen" of the University of Kaiserslautern) and
      M.Z. also thanks the Studienstiftung des Deutschen Volkes for fellowships.

PMID- 10941024
TI  - Triple-Decker Type Coordination of a Fullerene Trianion in

PMID- 10941025
TI  - The Valence Isomerization of Cyclooctatetraene to Semibullvalene We are most
      grateful to "Servicios Informaticos de la Universidad de Alcala", to Silicon
      Graphics, Inc. (Boston, MA) for computer facilities, and to Professors Jose-Luis
      Abboud (Instituto de Quimica Fisica "Rocasolano", C.S.I.C) and Julio Alvarez
      Builla (Departamento de Quimica Organica, Universidad de Alcala) for their
      generous and continuous support of our work. O.C. acknowledges financial support
      by the University of Alcala for a short stay in the King's College, London, and
      the D.G.E.S. (project number PM97-0074).

PMID- 10941026
TI  - Application of 3D-TOCSY-trNOESY for the Assignment of Bioactive Ligands from
      Mixtures This work was supported from the BMBF (FKZ 031161) and from the German
      Research Council (DFG, Sonderforschungsbereich 470, Teilprojekt B3). We thank the
      Fonds der Chemischen Industrie for generous support. We also thank Dr. T. Keller
      and Dr. G. Wolff (Bruker Analytik GmbH, Germany) for excellent support. Dr.
      Yasmin Karimi-Nejad (Solvay Pharmaceuticals, Netherlands) is thanked for helpful
      discussions.

PMID- 10941027
TI  - Natural-Product Hybrids: Design, Synthesis, and Biological Evaluation of Quinone
      Annonaceous Acetogenins This work was supported by the Deutsche Forschungs
      gemeinschaft, Fonds der Chemische Industrie, and ASTA-Medica AG.

PMID- 10941028
TI  - Synthesis of Trioxane Using Heteropolyacids as Catalyst.

PMID- 10941029
TI  - Enantioselective Synthesis of Functionalized 1,5-Cyclononadienes by
      Intramolecular Cycloalkylation under alpha,alpha'-Diallyl Coupling This work was
      supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 424)
      and the Fonds der Chemischen Industrie. A.D. gratefully acknowledges a fellowship
      from the Fonds der Chemischen Industrie. We thank Mrs. C. Weitkamp for her
      outstanding experimental assistance and Mr. J. Muller for his skillful work
      during a laboratory course.

PMID- 10941031
TI  - Preparation of Bioconjugates through an Ugi Reaction This work was financially
      supported by the Fonds der Chemischen Industrie and Aventis Research &
      Technologies, Frankfurt am Main.

PMID- 10941030
TI  - Tetraphenylphosphonium Hexaazidoarsenate(V): The First Structurally Characterized
      Binary As(V)-Azide Species Financial support by the Universitat Munchen and the
      Fonds der Chemischen Industrie is gratefully acknowledged. We are indebted to Dr.
      B. Krumm for recording the NMR spectra.

PMID- 10941032
TI  - u(4)-Peroxo versus Bis(u(2)-Hydroxo) Cores in Structurally Analogous
      Tetracopper(II) Complexes We thank Prof. Dr. G. Huttner for his generous and
      continuous support. Funding by the Deutsche Forschungsgemeinschaft as well as by
      the Fonds der Chemischen Industrie is gratefully acknowledged.

PMID- 10941033
TI  - The Use of Immobilized Templates-A New Approach in Molecular Imprinting.

PMID- 10941034
TI  - Synthesis and Reactivity of

PMID- 10941035
TI  - Metal-Based NO Sensing by Selective Ligand Dissociation This work was supported
      by a grant from the National Science Foundation and a fellowship to N.S. from the
      Undergraduate Research Opportunity Program (MIT). We thank Prof. Roger Tsien for
      valuable discussions at the inception of this project.

PMID- 10941037
TI  - A Transition State for the Enantioselective Deprotonation of N-Boc-Pyrrolidine
      with Isopropyllithium/(-)-Sparteine Chiral Diamines, Part 2. This investigation
      was supported by a grant from the National Institutes of Health. Part 1: ref. 6.

PMID- 10941036
TI  - Guest Penetration Deep within the Cavity of Calix

PMID- 10941038
TI  - Chiral Guests and Their Ghosts in Reversibly Assembled Hosts This work was
      supported by the Skaggs Research Foundation and the National Institutes of
      Health. The Administracion de Fomento Economico of Puerto Rico provided
      fellowship support to J.M.R. The Ministerio de Educacion y Cultura of Spain
      provided fellowship support to T.M. We thank Fraser Hof for assistance with
      molecular graphics design.

PMID- 10941039
TI  - A Supramolecular Solution to a Long-Standing Problem: The 1,6-Polymerization of a
      Triacetylene We thank Dr. Sergei Lymar of Brookhaven National Laboratories for
      assistance with the gamma irradiations, Drs. Alasdair F. Bell and Peter J. Tonge
      for assistance with the Raman spectroscopy, and the National Science Foundation
      for financial support.

PMID- 10941040
TI  - Mixed Ferrocene-Cobaltocenium Dendrimers: The Most Stable Organometallic Redox
      Systems Combined in a Dendritic Molecule This work was supported by the Direccion
      General de Ensenanza Superior e Investigacion Cientifica (PB-97-0001). We are
      grateful to M. J. Vicente and Dr. M. T. Alonso for valuable discussions on ESI
      MS.

PMID- 10941042
TI  - Nickel-Catalyzed Generation of Schiff Base Aluminum Enolate Initiators for
      Controlled Methacrylate Polymerization This work was supported by the Engineering
      and Physical Sciences Research Council (UK) and ICI Acrylics (now Ineos
      Acrylics).

PMID- 10941041
TI  - Structure of Homoleptic Cu(I)(CO)(3) Cations in Cu(I)-Exchanged ZSM-5 Zeolite: An
      X-ray Absorption Study This project was supported by MURST (Cofin 98, Area 03).
      XAFS measurements were performed at ESRF (European Synchrotron Radiation
      Facitity) within the public user program. BM8 GILDA beamline is supported by
      INFN, INFM and CNR. The European Community is gratefully acknowledged for a TMR
      grant to G.T.P. We are indebted to F. Danca for skilful technical support and to
      M. Benfatto for critical discussion.

PMID- 10941043
TI  - Reactive Intermediates on Metal Surfaces: A Ketene Monolayer on Single Crystal
      Platinum Generated by Photolysis of Pyridyl alpha-Diazoketones This research was
      supported financially by the Natural Science and Engineering Research Council of
      Canada (NSERC), The University of Western Ontario ADF, and the Canadian
      Foundation for Innovation. J.L.P thanks the NSERC for post graduate scholarships.

PMID- 10941044
TI  - Expanding the Scope of Protein Biosynthesis by Altering the Methionyl-tRNA
      Synthetase Activity of a Bacterial Expression Host Scott Ross was helpful in
      conducting the 1D TOCSY NMR experiments and Pratip Bhattachary is thanked for
      assistance in other NMR experiments. We are grateful to Yves Mechulam for a
      sample of plasmid pBSM547W305F and to Hieronim Jakubowski of UMDNJ-New Jersey
      Medical School, Newark, New Jersey, for plasmid pGG3. K.L.K. thanks the U.S.
      Department of Defense for a National Defense Science and Engineering Graduate
      Fellowship. This work was supported by grants from the Polymers and Genetics
      Programs of the National Science Foundation and from the U.S. Army Research
      Office.

PMID- 10941045
TI  - A Highly Efficient Triplet Analogue of a Thermal Biradical Cyclization-The
      Photochemical C(2)-C(6) Cyclization of Enyne-Heteroallenes We would like to
      express our gratitude to the Deutsche Forschungsgemeinschaft, the Fonds der
      Chemischen Industrie, and the Ministerio de Educacion y Ciencia (Spain) for
      generous support of this research.

PMID- 10941046
TI  - A Chiral Nonracemic Enolate with Dynamic Axial Chirality: Direct Asymmetric alpha
      Methylation of alpha-Amino Acid Derivatives This work was supported by a Grant-in
      Aid for Scientific Research on Priority Areas (No. 706: Dynamic Control of
      Stereochemistry) from the Ministry of Education (Monbusho), Japan.

PMID- 10941047
TI  - Generation of Heteroatom-Substituted Carbene Complexes of Iridium by Double C-H
      Activation of Ether and Amine Substrates This work was supported by the "Fonds
      zur Forderung der wissenschaftlichen Forschung" with a Schrodinger Stipendium for
      C.S. (J1756-CHE), the Spanish Ministry of Education (DGES, Project PB97-0733),
      and the Junta de Andalucia.

PMID- 10941048
TI  - DesVI: A New Member of the Sugar N,N-Dimethyltransferase Family Involved in the
      Biosynthesis of Desosamine The authors gratefully acknowledge financial support
      provided by the National Institutes of Health (GM 54346). H.-w.L. also thanks the
      National Institute of General Medical Sciences for a MERIT Award. L.Z. is the
      recipient of a Graduate School Dissertation Fellowship from the University of
      Minnesota.

PMID- 10941049
TI  - Surface-Confined Light Harvesting, Energy Transfer, and Amplification of
      Fluorescence Emission in Chromophore-Labeled Self-Assembled Monolayers This
      research was supported by the office of Naval Research, the AFOSR-MURI program,
      as well as fellowships from the Netherlands Scientific Organization (NWO), and
      from the Eastman Kodak Company, which are gratefully acknowledged.

PMID- 10941050
TI  - An Anthracene-Based Photochromic System That Responds to Two Chemical Inputs We
      thank the EPSRC (UK) for the award of a project studentship (to G.M.).

PMID- 10941051
TI  - Evidence for Cooperativity in the Disproportionation of H(2)O(2) Efficiently
      Catalyzed by a Tetranuclear Manganese Complex We thank the U.S. National
      Institutes of Health (GM38275) for financial support of this research.

PMID- 10941052
TI  - A Practical Asymmetric Synthesis of Enantiomerically Pure 3-Substituted
      Pyroglutamic Acids and Related Compounds This work was supported by grants from
      the U.S. Public Health Service (Grant DK 17420) and the National Institute of
      Drug Abuse (DA 06284 and DA 04248). The views expressed are those of the authors
      and not necessarily those of the USPHS.

PMID- 10941053
TI  - A Rapid Total Synthesis of Spirotryprostatin B: Proof of Its Relative and
      Absolute Stereochemistry F.v.N. gratefully acknowledges the Alexander-von
      Humboldt-Stiftung for a Feodor-Lynen fellowship that was kindly backed by Dr. R.
      Breslow as second host. This research was supported by the National Institutes of
      Health (Grant number HL 25848). We thank Dr. H. Osada (RIKEN) for providing us
      with spectra of the natural product. Furthermore we are grateful to Dr. D.
      Lichtblau from the Nakanishi laboratory for help with the CD spectra. We
      acknowledge the collaborative efforts of Ms. Maria Manzoni in these studies.

PMID- 10941055
TI  - New Syntheses with Oils and Fats as Renewable Raw Materials for the Chemical
      Industry.
AB  - Oils and fats are the most important renewable raw materials for the chemical
      industry. Hitherto, industrial oleochemistry has concentrated predominantly on
      the carboxy functionality of fatty acids but, more recently, modern synthetic
      methods have been applied extensively to fatty compounds for the selective
      functionalization of the alkyl chain. Radical, electrophilic, nucleophilic, and
      pericyclic as well as transition metal catalyzed additions to the C-C double bond
      of, for example, oleic acid as the prototype of a readily accessible, unsaturated
      fatty acid have led to a large number of novel fatty compounds from which
      interesting properties are expected. Functionalization of C-H bonds in the alkyl
      chain is also feasible with remarkable selectivity. Effective and highly
      versatile catalysts for the metathesis of esters of unsaturated fatty acids have
      been developed, which lead to new and interesting omega-unsaturated fatty acids.
      The epoxidation of unsaturated fatty acids has been developed extensively.
      Enzymatic reactions allow syntheses with high selectivity and yield of mono- and
      diglycerides and esters of carbohydrates with a variety of surfactant properties.
      Regio- and enantioselective microbial hydrations and hydroxylations widen the
      spectrum of selective reactions. Of considerable significance is that, with the
      use of gene technology, natural oils and fats have been improved significantly
      and will be improved still further, insofar as they show a more uniform and often
      unusual fatty acid spectrum. Numerous fatty acids are now available in a purity
      which makes them attractive for synthesis and as raw materials for the chemical
      industry.

PMID- 10941056
TI  - Properties and Synthetic Applications of Enzymes in Organic Solvents.
AB  - Biotransformations already represent an effective and sometimes preferable
      alternative to chemical synthesis for the production of fine chemicals and
      optically active compounds. To further widen the versatility of the biological
      approach, the so-called "nonaqueous enzymology", which now represents an
      important area of research and biotechnological development, has emerged in the
      last ten years or so. This new methodology is especially suitable for the
      modification of precursors of pharmaceutical compounds and fine chemicals, which,
      in most cases, are insoluble or poorly soluble in water. Even though the idea of
      carrying out an enzymatic process in organic solvent was initially considered
      with scepticism, biocatalysis in such media is now investigated and exploited in
      numerous academic and industrial laboratories. One of the reasons that makes
      enzymatic catalysis in nonaqueous media so appealing, is the important new
      properties that enzymes exhibit in organic solvents. For example, they are often
      more stable and can catalyze reactions that are impossible or difficult in water.
      Furthermore, enzyme selectivity can also differ from that in water and can
      change, or even reverse, from one solvent to another. This phenomenon, which can
      be called "medium engineering", can be exploited as a valid alternative to
      protein engineering. The first part of this review examines the thermodynamic,
      kinetic, spectroscopic, and physical approaches that have been adopted to
      investigate the factors that affect activity, stability, structure, and
      selectivity of enzymes in organic solvents. These combined studies have brought
      the understanding of enzyme catalysis in organic solvents to a level almost
      comparable to that reached for biocatalysis in aqueous media. The second part
      surveys a number of the synthetic applications of enzymes in organic media, which
      span from the preparation of milligrams of specifically labeled compounds to the
      modification of fats on multiton scale and from the preparation of complex key
      intermediates for the pharmaceutical industry to the synthesis of polymers.

PMID- 10941057
TI  - Paradigms Lost and Paradigms Found: Examples of Science Extraordinary and Science
      Pathological-And How To Tell the Difference The author thanks Bill Millard,
      editor of Columbia University's 21C magazine, for his excellent assistance and
      collaboration. The support of the NSF (Grant CHE98-12676) is gratefully
      acknowledged.

PMID- 10941058
TI  - beta-Catenin, Cyclins, and More: New Insights into the Pathogenesis, Treatment,
      and Prevention of Colon Cancer.

PMID- 10941059
TI  - New Functional Materials Based on Self-Assembling Organogels: From Serendipity
      towards Design The Royal Netherlands Academy of Science is gratefully
      acknowledged for a fellowship for J.H.v.E.

PMID- 10941060
TI  - Alkyl-Substituted Shape-Persistent Macrocycles: The First Discotic Liquid Crystal
      Composed of a Rigid Periphery and a Flexible Core A part of this work was
      supported by the Volkswagen-Stiftung. S.H. thanks the Fonds der Chemischen
      Industrie and the GDCh (Dr. Hermann Schnell-Stiftung) for support.

PMID- 10941061
TI  - De Novo Prediction of Inorganic Structures Developed through Automated Assembly
      of Secondary Building Units (AASBU Method) This work was supported by Centre
      National de la Recherche Scientifique. We thank F. J. J. Leusen, G. Engel, and A.
      K. Cheetham for useful assistance and discussions.

PMID- 10941062
TI  - Template-Induced, Stereoselective Cyclizations in the Cyclopolymerization of
      TADDOL-Dimethacrylate This work was supported by the Fonds der Chemischen
      Industrie.

PMID- 10941063
TI  - Bicyclo

PMID- 10941064
TI  - Regioselective alpha-Phosphorylation of Aldoses in Aqueous Solution Chemistry of
      alpha-aminonitriles, Part 29. Part 28: Ref. 1, Part 27: Ref. 2. This work was
      supported by the Skaggs Foundation. S.G. thanks the NASA NSCORT Exobiology
      program (La Jolla) for a postdoctoral fellowship.

PMID- 10941065
TI  - A New Gold-Catalyzed C-C Bond Formation This work was supported by the Deutsche
      Forschungsgemeinschaft (Ha 1932/5-1, Ha 1932/6-1) and the Fonds der Chemischen
      Industrie. Gold salts were donated by Degussa-Huls AG. A.S.K.H. is indebted to
      Prof. M. Gobel for laboratory space.

PMID- 10941066
TI  - alpha-Trialkylsilyl-Substituted alpha-Amino Acids This work was financially
      supported by the Fonds der Chemischen Industrie and Degussa-Huls. We are grateful
      to Dr. P. Phansavath for preliminary studies in this field.

PMID- 10941067
TI  - Total Synthesis of Bryostatin 3 This work was supported by the Ministry of
      Education, Science, Sports, and Culture (Japan). K.O. is grateful to JSPS for a
      predoctoral fellowship. The authors thank Dr. G. N. Chmurny (NIH) for providing
      them with (1)H and (13)C NMR spectra of bryostatin 3 and for helpful discussions.

PMID- 10941069
TI  - Distance-Dependent Electron Transfer in Au/Spacer/Q-CdSe Assemblies.

PMID- 10941068
TI  - Highly Diastereoselective Synthesis of Monocyclic and Bicyclic Secondary
      Diorganozinc Reagents with Defined Configuration We thank the DFG (SFB 260,
      Leibniz-Program) and the Fonds der Chemischen Industrie for generous support
      (Kekule-scholarship for E. H.). We thank BASF, Degussa-Huls AG, and Chemetall
      GmbH AG for the generous gift of chemicals.

PMID- 10941071
TI  - Enantioselective Intramolecular

PMID- 10941070
TI  - Purification and Partial Characterization of Tryptophan 7-Halogenase (PrnA) from
      Pseudomonas fluorescens This work was supported by the Deutsche
      Forschungsgemeinschaft (DFG) through the Graduiertenkolleg "Struktur-Eigenschafts
      Beziehungen bei Heterocyclen", the Environment and Climate Research and
      Technology Development Programme of the European Union, the Sachsische
      Staatsministerium fur Umwelt und Landesentwicklung, the Max-Buchner-Stiftung, and
      the Fonds der Chemischen Industrie. Samples of P. fluorescens BL915DeltaORF1-4
      with pPEH14(prnA) and pPEH14(prnC) were obtained from Dr. J. M. Ligon, Novartis
      Agribusiness Biotechnology Research, Inc., Research Triangle, NC (USA) and NADH
      oxidase (from Thermus thermiphilus) from Prof. Helmut Erdmann, Fachhochschule
      Flensburg (Germany).

PMID- 10941072
TI  - The Rhodium-Catalyzed Cyclotetramerization of Butadiene: Isolation and Structural
      Characterization of an Intermediate This work was supported by the Deutsche
      Forschungsgemeinschaft (SFB 347). K.I. thanks the Fonds der Chemischen Industrie
      for a Ph.D. scholarship.

PMID- 10941073
TI  - Novel 1,2,4-Triphosphole and 1,2,3-Triphosphetene Derivatives from N,N'-Bis(2,2
      dimethylpropyl)benzimidazolin-2-ylidene and Phosphaalkynes This work was
      supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
      Industrie.

PMID- 10941074
TI  - Designing a Heterogeneous Catalyst for the Production of Adipic Acid by Aerial
      Oxidation of Cyclohexane This work was supported by an EPSRC rolling grant to
      J.M.T. We thank the CLRC for the synchrotron beam time and other facilities at
      Daresbury Laboratory.

PMID- 10941075
TI  - Designing a Molecular Sieve Catalyst for the Aerial Oxidation of n-Hexane to
      Adipic Acid We gratefully acknowledge helpful discussions with Dr. R. G. Bell and
      Prof. C. R. A. Catlow, the support (via a rolling grant to J.M.T.) of the EPSRC,
      and the award of a research fellowship (for G.S.) from the Leverhulme Foundation.

PMID- 10941076
TI  - Controlled Assembly of Dinuclear Metallacycles into a Three-Dimensional Helical
      Array This work was supported by the CVCP (Overseas Research Student Scheme) (to
      A.N.K.), the EPSRC, and the University of Nottingham.

PMID- 10941077
TI  - A Dodecanuclear Copper(II) Cage Containing Phosphonate and Pyrazole Ligands This
      work was supported by a grant from the Department of Science and Technology
      (DST), New Delhi (V.C.). V.C. is also grateful to the Homi Bhabha Fellowship
      Council for a fellowship. We thank the DST for funding the National Facility for
      X-ray Crystallography at the Indian Institute of Technology, Kanpur. We thank
      Prof. Dr. P. K. Bharadwaj for his help in the data collection and X-ray analysis,
      and Prof. Dr. A. R. Chakravorthy, Department of Inorganic and Physical Chemistry,
      Indian Institute of Science, Bangalore, India for the magnetic measurements on 1.

PMID- 10941078
TI  - Phenyl/Pentafluorophenyl Interactions and the Generation of Ordered Mixed
      Crystals: sym-Triphenethynylbenzene and sym-Tris(perfluorophenethynyl)benzene
      This work was supported by the US National Science Foundation (CHE-9904275).

PMID- 10941079
TI  - Inorganic-Organic Hybrid Materials Constructed from

PMID- 10941080
TI  - Salen as a Chiral Activator: anti versus syn Switchable Diastereoselection in the
      Enantioselective Addition of Crotyl Bromide to Aromatic Aldehydes We thank the
      CNR (Rome), M.U.R.S.T. (Rome) "Progetto Stereoselezione in Chimica Organica,
      Metodologie ed Applicazioni", and the University of Bologna (funds for selected
      research topics) for financial support of this research.

PMID- 10941081
TI  - A Designed beta-Hairpin Containing a Natural Hydrophobic Cluster This research
      was supported by the National Science Foundation (CHE-9820952). J.F.E. was
      supported by a fellowship from the Ministerio de Educacion y Cultura (Spain) and
      the Fulbright Commission. The mass spectrometer was purchased in part with a
      National Science Foundation grant (CHE-9520868), and the NMR spectrometers were
      purchased in part with a National Institute Of Health grant (1 S10 RR04981). The
      CD spectrometer and analytical ultracentrifuge are part of the UW Biophysics
      Instrumentation Facility (NSF BIR-9512577).

PMID- 10941082
TI  - Complimentary Polytopic Interactions Complimentary Polytopic Interactions, Part
      1. This work was supported by BDH (Merck Ltd.) and the EPSRC. The
      photoconductivity experiment and synthesis of large-core molecules 2 and 3 are
      reported elsewhere.4, 12.

PMID- 10941083
TI  - Rhodium-Rhodium Bonds in Edge-Sharing Coplanar Dinuclear Complexes Generous
      financial support from DGES (Projects PB98-641, PB95-318, and PB94-1186) and a
      fellowship (to M.S.) are gratefully acknowledged.

PMID- 10941084
TI  - Synthesis of chiral, enantiopure zirconocene imido complexes: highly selective
      kinetic resolution and stereoinversion of allenes, and evidence for a stepwise
      cycloaddition/retrocycloaddition reaction mechanism.

PMID- 10941085
TI  - Oxygenation of Hydrocarbons Mediated by Mixed-Valent Basic Iron Trifluoroacetate
      and Valence-Separated Component Species under Gif-Type Conditions Involves Carbon
      and Oxygen-Centered Radicals This work was supported by the U.S. Environmental
      Protection Agency and the NIH/NIEHS (superfund).

PMID- 10941086
TI  - Synthesis, Characterization, and Catalytic Activity of a Large-Pore
      Tridirectional Zeolite, H-ITQ-7 We thank the Spanish CICYT for financial support
      (Project MAT97-1016-C02-01).

PMID- 10941087
TI  - Infinite, Linear, Unbranched Borynide Chains in LiB(x)-Isoelectronic to Polyyne
      and Polycumulene The financial support by the Swiss National Science Foundation
      (projects 21-36586.92 and 4030-032775) is gratefully acknowledged. We thank Dr.
      V. Shklover for SEM pictures, Dr. M. Spahr for magnetic measurements, Dr. T.
      Chatterij and Dr. E. Souard for the neutron diffraction experiments, and Prof.
      Dr. S. Roth, Prof. Dr. H. Kuzmany, Prof. H. D. Lutz, and Dr. E. Suchanek for
      spectroscopic investigations.

PMID- 10941088
TI  - A New, Simple Route to Novel Gold Clusters: Structure of an Au(6)Ag Wheel with a
      Gold Rim This research was supported by the Direccion General de Ensenanza
      Superior (PB 98-0542) and the Engineering and Physical Sciences Research Council.

PMID- 10941089
TI  - Photoregulation of the DNA Polymerase Reaction by Oligonucleotides Bearing an
      Azobenzene We should like to thank Professor Kazunari Taira for valuable
      comments. This work was partially supported by the Grant-in-Aid for Scientific
      Research from the Ministry of Education, Science, and Culture, Japan (Molecular
      Synchronization for Design of New Materials System). The support of the grant
      from the "Research for the Future" Program of the Japan Society for the Promotion
      of Science (JSPS-RFTF97I00301) is also acknowledged.

PMID- 10941090
TI  - A Convenient Synthesis of alpha-Halomethylene Aldols or beta-Halo-alpha
      (hydroxyalkyl)acrylates Using the Chalcogeno-Baylis-Hillman Reaction This work
      was supported in part by a Grant-in-Aid for Scientific Research (Priority Areas
      Nos. 10133244 and 11120247) from the Ministry of Education, Science, Sports, and
      Culture, Japan.

PMID- 10941091
TI  - Base-Specific Minor Groove Site Binding in Metallo-Nucleobase Polymers This work
      was financially supported by the EPSRC and the BBSRC. The EPSRC mass spectrometry
      service at the University of Wales, Swansea, is acknowledged.

PMID- 10941092
TI  - Coordinated and Clathrated Molecular Diiodine in

PMID- 10941093
TI  - Thermosensitive, Reversibly Cross-Linking Gels with a Shape "Memory"

PMID- 10941095
TI  - Microchips as Controlled Drug-Delivery Devices.
AB  - Controlled-release systems are common in a number of product areas, including
      foods, cosmetics, pesticides, and paper. Microencapsulated systems, for example,
      are used for the release of flavors and vitamins in foods, fragrances in
      perfumes, and inks in carbonless copy paper. Controlled-release systems for drug
      delivery first appeared in the 1960s and 1970s. In the past three decades, the
      number and variety of controlled release systems for drug-delivery applications
      has increased dramatically. Many of these use polymers having particular physical
      or chemical characteristics such as biodegradability, biocompatibility, or
      responsiveness to pH or temperature changes. However, recent advances in the
      field of microfabrication have created the possibility of a new class of
      controlled-release systems for drug delivery, namely, that of small, programmable
      devices. Their small size, potential for integration with microelectronics, and
      ability to store and release chemicals on demand could make controlled-release
      microchips useful in a number of areas, including medical diagnostics, analytical
      chemistry, chemical detection, industrial process monitoring and control,
      combinatorial chemistry, microbiology, and fragrance delivery. More importantly,
      drug-delivery microchips resulting from this convergence of controlled release
      and microfabrication technologies may provide new treatment options to clinicians
      in their fight against disease.

PMID- 10941096
TI  - Hypervalent Bonding in One, Two, and Three Dimensions: Extending the Zintl-Klemm
      Concept to Nonclassical Electron-Rich Networks.
AB  - We construct a theory for electron-rich polyanionic networks in the intermetallic
      compounds of heavy late main group elements, building a bonding framework that
      makes a connection to well-understood hypervalent bonding in small molecules such
      as XeF(4), XeF(2), and I(3)(-). What we do is similar in spirit to the analogy
      between the Zintl-Klemm treatment of classical polyanionic networks and the octet
      rule for molecules. We show that the optimal electron count for a linear chain of
      a heavy main group element is seven electrons per atom, six electrons per atom
      for a square lattice, and five electrons per atom for a simple cubic lattice.
      Suggestions that these electron counts are appropriate already exist in the
      literature. We also derive electron counts for more complicated topologies,
      including one-dimensional ladders and one dimensional strips cut from a square
      lattice. We also study pairing (Peierls) distortions from these ideal geometries
      as well as other deformations. The presence of s-p mixing (or its absence) plays
      a critical role in the propensity for pairing and, in general, in determining the
      geometrical and electronic structure of these phases. Hypervalent bonding goes
      along with the relative absence of significant s-p interaction; there is a
      continuum of such mixing, but also a significant difference between the second
      row and heavier elements. We attribute the existence of undistorted metallic
      networks of the latter elements to diminished s-p mixing, which in turn is due to
      the contraction of less-screened s orbitals relative to p orbitals down the
      groups in the Periodic Table. The number of electrons in the polyanionic network
      may be varied experimentally. An important general principle emerges from our
      theoretical analysis: upon oxidation a hypervalent structure transforms into a
      classical one with the same lattice dimensionality, while upon Peierls distortion
      the hypervalent structures transform into classical ones with the lattice
      dimensionality reduced. Dozens of crystal structure types, seemingly unrelated to
      each other, may be understood using the unifying concept of electron-rich
      multicenter bonding. Antimonides, which are explored in great detail in the
      current work, conform particularly well to the set of electron counting rules for
      electron-rich nonclassical networks. Some deviation up and down from the ideal
      electron count is exhibited by known stannides and tellurides. We can also make
      sense of the bonding in substantially more complicated alloys, including
      La(12)Mn(2)Sb(30) and Tl(4)SnTe(3). The hypervalent electron counting scheme
      developed in this paper, along with the classical Zintl-Klemm electron counting
      rules, gives an easy qualitative understanding of bonding in a wide variety of
      intermetallic compounds of heavy main group elements.

PMID- 10941097
TI  - Was Leonardo a Chemist? This work was supported by the Ministry of Education and
      Cultura (D.G.I.C.Y.T., grant PB98-0997). I am grateful to the Britannica Center,
      Chicago, for kindly providing further information on the biographies and
      scientific contributions of Leonardo da Vinci.

PMID- 10941098
TI  - Building Photogenic Molecules-Molecules Made for Direct Individual Observation
      The author thanks Teri Odom and Charles Lieber (Harvard University), and Ken-ichi
      Sugiura and Yoshiteru Sakata (Osaka University) for supplying STM images for
      Figures 1 a and 1 c of this article.

PMID- 10941099
TI  - Oligopyridine Liquid Crystals-Novel Building Blocks for Supermolecular
      Architectures Based on Metal Coordination and Hydrogen Bonding.

PMID- 10941100
TI  - Five- and Seven-Membered Rings from Alkenyl(methoxy)carbene Complexes and Methyl
      Ketone Enolates This work was supported by DGICYT (Grant PB97-1271).

PMID- 10941101
TI  - Spectroscopic Evidence for a 4-Methylidene Imidazol-5-one in Histidine and
      Phenylalanine Ammonia-Lyases We thank Prof. G. E. Schulz and Dipl.-Chem. M.
      Baedeker (University of Freiburg) for providing us with the new PAL expression
      system and Dr. M. Stieger (Hoffmann-La Roche, Basel, Switzerland) for vector
      pREP4-GroESL carrying the HSP-60 system. D.R. and D.M. thank the Land of Baden
      Wurttemberg for a scholarship for graduate students. The work was supported by
      the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.

PMID- 10941102
TI  - Tris(pyrazolyl)methanesulfonates: A Novel Class of Water-Soluble Ligands.

PMID- 10941103
TI  - From Glucose to Cyclooctanic Carbaglucose: A New Class of Carbohydrate Mimetics.

PMID- 10941104
TI  - A Silver(I) Coordination Polymer Chain Containing Nanosized Tubes with Anionic
      and Solvent Molecule Guests This work was supported by the National Nature
      Science Foundation of China. M.C.H. thanks the Croucher Foundation of Hong Kong
      for financial support.

PMID- 10941105
TI  - Methanophenazine: Structure, Total Synthesis, and Function of a New Cofactor from
      Methanogenic Archaea This work was supported by the Deutsche
      Forschungsgemeinschaft (Sonderforschungsbereich 416; grants De 488/6-1 and De
      488/4-2) and the Fonds der Chemischen Industrie. We are grateful to Drs. J. Paust
      and H. Jaedicke (BASF AG, Ludwigshafen) and Dr. R. K. Muller (Hoffmann-La Roche
      Ltd., Basel) for generously providing chemicals.

PMID- 10941106
TI  - First Artificial Receptor for Caffeine-A New Concept for the Complexation of
      Alkylated Oxopurines This work was supported by the Fonds der Chemischen
      Industrie (Liebig fellowships for S.R.W. and C.A.S.) and the Deutsche Akademie
      der Naturforscher Leopoldina/BMBF (postdoctoral fellowship for C.A.S.). We are
      particularly grateful to Prof. Dr. Julius Rebek, Jr. for fruitful discussions and
      all his support for this project.

PMID- 10941107
TI  - Calcium-Catalyzed Selective and Quantitative Transformation of CH(4) and CO into
      Acetic Acid This work was supported in part by the Grants-in-Aid for Scientific
      Research on Priority Area No. 283 "Innovative Synthetic Reactions" and Scientific
      Research (A) No. 09355031 from the Ministry of Education, Science, Sports, and
      Culture of Japan (Monbusho). M.A. thanks the Monbusho for financial support.

PMID- 10941108
TI  - BABAR-Phos Rhodium Complexes: Reversible Metal Insertion into a Three-Membered
      Ring and Catalytic Hydroborations This work was supported by the ETH Zurich and
      the National Swiss Science Foundation.

PMID- 10941109
TI  - Halogen-Magnesium Exchange via Trialkylmagnesates for the Preparation of Aryl-
      and Alkenylmagnesium Reagents This work was supported by a Grant-in-Aid for
      Scientific Research from the Ministry of Education, Science, Sports, and Culture,
      Japan.

PMID- 10941110
TI  - Lactone Formation by Rhodium-Catalyzed C-C Bond Cleavage of Cyclobutanone We
      thank Dr. T. Tanaka (Kyoto University) for GC analysis of H(2), and Dr. M. Miura
      (Osaka University) for helpful discussions. Support from Monbusho (Grant-in-Aid
      for Scientific Research on Priority Areas, No. 283: Innovative Synthetic
      Reactions) is gratefully acknowledged.

PMID- 10941111
TI  - Ligand Electronic Effect in Enantioselective Palladium-Catalyzed Copolymerization
      of Carbon Monoxide and Propene This work was supported by the ETH Zurich. We
      thank Novartis AG and Solvias AG, Basel, for the donation of chemicals.

PMID- 10941112
TI  - Versatile Indole Synthesis by a 5-endo-dig Cyclization Mediated by Potassium or
      Cesium Bases We thank the DFG (Leibniz-Programm) and the Fonds der Chemischen
      Industrie for generous financial support. A.L.R. and C. K. thank the Humboldt
      Foundation and the BASF AG, respectively, for fellowships. W.D. was supported by
      the BMBF program (03 D 0056 2). We thank Dr. J. Henkelmann (BASF AG) for helpful
      discussions and the BASF AG for the generous gift of chemicals.

PMID- 10941113
TI  - Novel Synthesis of Borane Complexes of Cyclic Phosphanes Using Ruthenium
      Catalyzed Olefin Metathesis This work was supported by the European Community
      Training and Mobility Research Programme (COSSAC, ERBFMRXCT 980193 to M.S.) and
      by the Nuffield Foundation (NAL/00046/G).

PMID- 10941114
TI  - Total Synthesis of Luzopeptin E2 This work was supported by the NIH (CA-55268),
      the NSF (CHE 95-26183), the R. A. Welch Foundation (C-1007), the A. P.Sloan
      Foundation (fellowship to M.A.C., 1994-1998), the MENRT, the CNRS, and the Region
      Rhone-Alpes. We are grateful to Ms. Laurence Rousset and Dr. Denis Bouchu for
      recording the mass spectral data.

PMID- 10941115
TI  - A Third-Generation Bicyclopropylidene: Straightforward Preparation of 15,15'
      Bis(hexaspiro

PMID- 10941116
TI  - Cross-Linked Scandium-Containing Dendrimers: A New Class of Heterogeneous
      Catalysts.

PMID- 10941117
TI  - A New Palladium-Catalyzed Intramolecular Cyclization: Synthesis of 1-Aminoindole
      Derivatives and Functionalization of their Carbocylic Rings.

PMID- 10941118
TI  - Spin Crossover in a Supramolecular Fe(4)(II)

PMID- 10941119
TI  - Ag(3)SnP(7): A Polyphosphide with a Unique <!

PMID- 10941120
TI  - Fixation of Dinitrogen to a Mesoscale Solid Salt Using a Titanium
      Oxide/Conducting Polymer System The authors thank T. Shibuya of Idemitsu Kosan
      Co. for help with the XPS analyses, F. Kaneuchi of JASCO for the FTIR
      measurements, and T. Tohara of Edax Japan K.K. for the energy dispersive X-ray
      analyses. Partial support of this work was provided by The Thermal and Electric
      Energy Technology Foundation.

PMID- 10941121
TI  - Fatty Acid-Oligo(ethylene glycol) Ester Forms Ion Channels in Lipid Membranes
      This contribution was supported by the Deutsche Forschungsgemeinschaft (SFB 424:
      Molekulare Orientierung als Funktionskriterium in chemischen Systemen).

PMID- 10941122
TI  - Aluminum Fluoride as a Storage Matrix for Atomic Hydrogen This work was supported
      by Deutsche Forschungsgemeinschaft and by the Fonds der Chemischen Industrie. We
      thank Dr. E. Janata (HMI Berlin), Dr. B. Ziemer, Dr. M. Pach and Dr. J. Bartoll
      (HU Berlin) for the assistance with the experimental work.

PMID- 10941123
TI  - Intermediate-Range Order in Amorphous Nitridic Ceramics: Lessons from Modern
      Solid-State NMR Spectroscopy This work was supported by the Deutsche
      Forschungsgemeinschaft (SFB 408).

PMID- 10941124
TI  - Tecto-RNA: One-Dimensional Self-Assembly through Tertiary Interactions This work
      was carried out in Strasbourg with the support of grants to N.B.L. from the NIH
      (1R15 GM55898) and the NIH Fogarty Institute (1-F06-TW02251-01) and the support
      of the CNRS to L.J. The authors wish to thank Eric Westhof for his support and
      encouragement of this work.

PMID- 10941125
TI  - Novel IBX-Mediated Processes for the Synthesis of Amino Sugars and Libraries
      Thereof We thank Dr. D. H. Huang, Dr. G. Siuzdak, and Dr. R. Chadha for NMR
      spectroscopic, mass spectrometric, and X-ray crystallographic assistance,
      respectively, and Prof. H. M. R. Hoffmann and Prof. A. Eschenmoser for helpful
      discussions. We also thank Dr. Maria-Rosa Rodriguez and Mr. Keith Wilcoxen of
      these laboratories for early intermediates leading to 9-12. This work was
      financially supported by the National Institutes of Health (USA), The Skaggs
      Institute for Chemical Biology, fellowships from the Ministerio de Educacion y
      Cultura, Spain (J.A.V.) and the National Science Foundation (P.S.B), and grants
      from Array Biopharma, Pfizer, GlaxoWellcome, Merck, Schering Plough, Hoffmann
      LaRoche, Boehringer Ingelheim, DuPont, and Abbott Laboratories.

PMID- 10941126
TI  - Novel Reactions Initiated by Titanocene Methylidenes: Deoxygenation of
      Sulfoxides, N-Oxides, and Selenoxides We thank Drs. D. H. Huang and G. Suizdak
      for NMR spectroscopic and mass spectroscopic assistance, respectively. Financial
      support for this work was provided by The Skaggs Institute for Chemical Biology,
      the National Institutes of Health (USA), fellowships from the National Science
      Foundation (S.A.S.) and the Alfred Benzons Foundation (K.B.S.), and grants from
      Abbott, Amgen, Boehringer-Ingelheim, GlaxoWellcome, Hoffmann-LaRoche, DuPont,
      Merck, Novartis, Pfizer, and Schering Plough.

PMID- 10941127
TI  - Asymmetric Synthesis of Phorboxazole B-Part I: Synthesis of the C(20)-C(38) and
      C(39)-C(46) Subunits Financial support was provided by the National Institutes of
      Health (GM-33328) and the National Science Foundation. An American Cancer Society
      Postdoctoral Fellowship to T.E.S. and an NSF Predoctoral Fellowship to V.J.C. are
      gratefully acknowledged. The NIH BRS Shared Instrumentation Grant Program 1-S10
      RR04870 and the NSF (CHE 88-14019) are acknowledged for providing NMR facilities.

PMID- 10941128
TI  - Asymmetric Synthesis of Phorboxazole B-Part II: Synthesis of the C(1)-C(19)
      Subunit and Fragment Assembly Financial support has been provided by the National
      Institutes of Health (GM-33328) and the National Science Foundation. The NIH BRS
      Shared Instrumentation Grant Program 1-S10-RR04870 and the NSF (CHE 88-14019) are
      acknowledged for providing NMR facilities.

PMID- 10941129
TI  - Asymmetric, Stereocontrolled Total Synthesis of Paraherquamide A This work was
      supported by the NIH (Grant CA 70375). The Japanese Society for the Promotion of
      Science (JSPS) is acknowledged for providing support to H.T. Mass spectra were
      obtained on instruments supported by the NIH Shared Instrumentation Grant (GM
      49631). We also wish to thank Dr. Timothy Blizzard (Merck & Co.) for providing an
      authentic sample of natural paraherquamide A. We also wish to acknowledge Dr.
      Byung H. Lee (Pharmacia-Upjohn Co.) for providing NMR spectra and an authentic
      specimen of 14-oxoparaherquamide B. We also wish to thank Dr. Alfredo Vazquez for
      assistance with purification and characterization of synthetic paraherquamide A.

PMID- 10941130
TI  - Hexanitroisobutene Dianion Salts This research was sponsored in part by the US
      Department of Energy IPP program under contract DE-AC05-96OR22464 with the Oak
      Ridge National Laboratory, managed by the Lockheed Martin Energy Research Corp.
      CNDO/2 calculations were performed by Dr. A. V. Belik and Dr. V. A.
      Shlyapochnikov (N. D. Zelinsky Institute of Organic Chemistry).

PMID- 10941131
TI  - Superacid-Catalyzed Selective Formylation-Rearrangement of Isoalkanes with Carbon
      Monoxide to Branched Ketones Chemistry in Superacids, Part 51. Part 50: G. A.
      Olah, G. Rasul, M. Hachoumy, A. Burrichter, G. K. S. Prakash, J. Am. Chem. Soc.
      2000, 122, 2737. Support of our work by the Loker Hydrocarbon Research Institute
      is gratefully acknowledged.

PMID- 10941132
TI  - Completely Fused Diporphyrins and Triporphyrin This work was supported by Grant
      in-Aids for Scientific Research (No. 11223205) from the Ministry of Education,
      Science, Sports, and Culture of Japan and by CREST (Core Research for Evolutional
      Science and Technology) of Japan Science and Technology Corporation (JST). A.T.
      thanks the JSPS Research Fellowship for Young Scientists. We also thank Dr. M.
      Shiro of the Rigaku Corporation for his help in obtaining the single-crystal X
      ray data of 5.

PMID- 10941133
TI  - What Is the Structure of Glabrescol? Stereoselective Synthesis of Reported
      Glabrescol We thank Professor Jacobs, University of the West Indies, for the NMR
      spectra of natural glabrescol. This work was supported by a Grant-in-Aid for
      Scientific Research (No. 11672132) from the Ministry of Education, Science,
      Sports, and Culture of Japan.

PMID- 10941134
TI  - Beneficial Effect of ortho-Methoxy Groups in the Asymmetric Ring Opening of meso
      Epoxides with Silicon Tetrachloride Catalyzed by Chiral ortho
      Methoxyphenyldiazaphosphonamide Lewis Bases We thank the CNRS for financial
      support. O.L. acknowledges the CNRS and Region PACA for a doctoral fellowship. We
      thank Dr. M. Giorgi and Prof. M. Pierrot for their kind assistance with the X-ray
      analysis of compound 1 and Dr. A. Tenaglia for fruitful discussions.

PMID- 10941135
TI  - Nicotine-induced excitation of midbrain dopamine neurons in vitro involves
      ionotropic glutamate receptor activation.
AB  - Presynaptic nicotinic acetylcholine receptors (nAChR) on glutamatergic as well as
      GABAergic synaptic terminals are considered to play a major role in mediating
      nicotinic effects on neurons in many parts of the brain. However, to what extent
      the excitatory effect of nicotine on the dopamine (DA) neurons in the ventral
      tegmental area (VTA) is mediated via their glutamatergic input remains unclear.
      The excitatory effect of nicotine on these cells was therefore studied by means
      of intracellular recordings from a midbrain slice preparation in the presence of
      antagonists to NMDA and non-NMDA receptors and compared to the effect of nicotine
      alone. Our results show that the excitatory effect of nicotine is markedly
      reduced both in the presence of 2-amino-5-phosphonopentanoic acid (AP5) and 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX), i.e., from 115 +/- 14.3% to 63.4 +/-
      11.0% and 63.2 +/- 13.6%, respectively. The coapplication of both antagonists did
      not have an additional effect in reducing the nicotine-induced increase in firing
      frequency. These findings clearly indicate that ionotropic glutamate receptor
      activation partly, but not entirely, mediates the excitatory effect of nicotine
      on DA neurons in VTA. In addition, we have pharmacologically characterized the
      nicotinic effect by the use of different nAChR antagonists, i.e., dihydro-beta
      erythroidine (DHBE), mecamylamine, and methyllycaconitine (MLA). DHBE and
      mecamylamine but not MLA completely blocked the effect of nicotine, indicating
      that nAChRs other than alpha(7)-subtype are involved in the nicotine-induced
      excitation of the dopamine neurons in the brain slice preparation.

PMID- 10941136
TI  - Nicotinic receptor-mediated regulation of dopamine transporter activity in rat
      prefrontal cortex.
AB  - The objective of this study was to determine whether nicotine could selectively
      influence dopamine levels in the prefrontal cortex as compared with other
      dopaminergic areas of brain. Using a superfusion system, we found that nicotine
      and other agonists at nicotinic acetylcholine receptors enhanced the release of
      radiolabeled dopamine that was stimulated by 10 microM amphetamine from slices
      prepared from rat prefrontal cortex. In contrast, nicotine had no effect on
      amphetamine-stimulated [(3)H]dopamine release from slices of nucleus accumbens
      nor striatum. Under the conditions used, which included no added calcium to
      exclude contribution by exocytotic release, nicotine had no effect on basal
      release of [(3)H]dopamine. The enhancement by nicotine was concentration
      dependent, reaching a maximum at 5 microM, and producing less release at higher
      concentrations. Enhancement by nicotine was fully reversed by 30 microM dihydro
      beta-erythroidine, and by 10 microM mecamylamine, but was not affected by alpha
      bungarotoxin. The potencies of nicotine, epibatidine, cytisine, and A85380 to
      enhance amphetamine-stimulated dopamine release, as well as the sensitivity of
      nicotine enhanced release to antagonists, are consistent with mediation via a
      high-affinity nicotinic acetylcholine receptor containing alpha 4 and beta 2
      subunits, the major species of nicotinic receptor in forebrain. Since low
      dopaminergic activity in prefrontal cortex is correlated with cognitive deficits
      in schizophrenia, our findings may help explain why these deficits are improved
      in schizophrenics by smoking or nicotine administration.

PMID- 10941137
TI  - Differential effects of coadministration of fluoxetine and WAY-100635 on
      serotonergic neurotransmission in vivo: sensitivity to sequence of injections.
AB  - Serotonin 5-HT(1A) receptor antagonists potentiate the effects of serotonin
      reuptake inhibitors on extracellular serotonin levels in a variety of brain
      regions. These effects are quite variable, however, with reports indicating
      potentiations of anywhere from 100-1900%. One factor that might impact the
      magnitude of such potentiations is the timing of administration of the two
      agents; reports in which the reuptake inhibitor is given prior to the serotonin
      receptor antagonist consistently report larger potentiations than reports in
      which the antagonist is given first. To test this relationship directly,
      microdialysis and electrophysiology studies were performed to assess the
      magnitude of increase in extracellular serotonin and changes in cellular activity
      produced by the serotonin reuptake inhibitor fluoxetine and the 5-HT(1A) receptor
      antagonist WAY-100635 under various dosing regimens. In microdialysis studies,
      when WAY-100635 (0.5 mg/kg s.c.) was administered 80 min after fluoxetine (10
      mg/kg i.p.) the increase in serotonin was more than twice that observed when the
      compounds were coadministered. In electrophysiology studies in vivo, WAY-100635
      reversed the depression of cell firing produced by fluoxetine when administered
      30 min after fluoxetine, but when the two compounds were coadministered, a
      depression in firing rate was observed comparable to that produced by fluoxetine
      alone. In contrast, slice recording studies showed that WAY-100635 blocked the
      effects of fluoxetine regardless of the order of administration. These results
      indicate that fluoxetine and WAY-100635 can interact in a fashion not predicted
      by the currently accepted model. It is likely that neuronal circuitry outside of
      the raphe nuclei underlies this relationship.

PMID- 10941139
TI  - Multisecond oscillations in the subthalamic nucleus: effects of apomorphine and
      dopamine cell lesion.
AB  - Clinical and preclinical data indicate that the subthalamic nucleus (STN) plays a
      critical role in mediating the hyper- and hypoactive behavioral states associated
      with increases and decreases in dopamine receptor stimulation in the basal
      ganglia. The present study investigates effects of dopamine receptor stimulation
      on slow multisecond oscillations in firing rates in STN neurons. Extracellular,
      single-unit recordings were performed in locally anesthetized and immobilized
      rats which were either intact or had received unilateral 6-OHDA lesions of the
      medial forebrain bundle. The majority (64%) of spike trains recorded from STN
      neurons exhibited periodic oscillations in firing rate within the range of 2-60
      sec, with an average period of 24 sec. The distribution of these baseline
      periodicities was not altered by unilateral 6-OHDA lesion, but periods were
      significantly shortened by systemic administration of the D1/D2 agonist
      apomorphine. This effect was observed in a greater proportion of neurons recorded
      from 6-OHDA-lesioned rats as compared to intact rats, was notably diminished in
      rats systemically anesthetized with chloral hydrate, and did not correlate with
      drug-induced changes in firing rate. These oscillations are similar to slow
      periodicities in firing rate recently reported in other basal ganglia nuclei. The
      possibility that these periodic oscillations in firing rate play a significant
      role in basal ganglia function was supported by the observation that the time of
      onset of apomorphine induced alterations in amplitude and periodicity of slow
      oscillations in STN spike trains is coincident with the onset of behavioral
      effects of this drug in 6-OHDA-lesioned animals. Synapse 38:38-50, 2000.
      Published 2000 Wiley-Liss, Inc.

PMID- 10941138
TI  - Piperazine analog of vesamicol: in vitro and in vivo characterization for
      vesicular acetylcholine transporter.
AB  - The probes to detect vesicular acetylcholine transporter (VAChT) in vivo are
      important to evaluate the mapping and function in cholinergic system. To develop
      high-specific and high-affinity radiotracer for single photon emission computed
      tomography, we investigated piperazine analogs which replaced the piperidine ring
      of (-)-vesamicol with a piperazine ring. We found that the piperazine analog of
      iodobenzovesamicol, trans-5-iodo-2-hydroxy-3-[4-phenylpiperazinyl] tetralin
      (DRC140), had high affinity for VAChT in rat brain. We carried out binding assay
      in subcellular fraction of the rat brain. The highest B(max) for [(125)I]-DRC140
      binding was observed in the synaptic vesicle fraction (1,751 fmol/mg protein),
      followed by the crude vesicle (821 fmol/mg protein) and the P2 fraction (187
      fmol/mg protein). These K(d) values were similar to the affinity of highly
      purified synaptic vesicular fraction (K(d) = 0.3 nM) with a one-site model. The
      possibility that [(125)I]-DRC140 recognizes sigma receptor was excluded by our
      finding large inhibition constants (K(i) = 849 nM for haloperidol, K(i) = 3,052
      nM for 1,3-di(2-tolyl)guanidine). In vivo distribution studies with the [(123)I]
      DRC140 in rats showed a rapid brain uptake. The highest brain area was in
      striatum, followed by frontal cortex, occipital cortex, and hippocampus. The
      lowest brain area was cerebellum. The radioactivity of high-accumulated areas in
      ex vivo autoradiography was reduced by a preinjection of (-)-vesamicol and these
      levels were reduced to the radioactivity in cerebellum. These results show that
      [(125)I]-DRC140 can provide extremely high specific tracer with excellent brain
      permeability as a ligand for single photon emission computed tomography.

PMID- 10941140
TI  - Differential expression of GABA(A) receptor subunit mRNAs and ligand binding
      sites in rat brain following phencyclidine administration.
AB  - Recent biochemical observations have suggested the abnormalities in the gamma
      amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present
      study, we investigated the subunits gene expressions and ligand binding of the
      GABA(A) receptor following acute and chronic administration of phencyclidine
      (PCP), which induces schizophrenia-like symptoms, in rats using in situ
      hybridization and in vitro quantitative autoradiography. PCP i.p. administration
      at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of
      alpha 1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (
      6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate
      gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations
      for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3
      mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal
      cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebellum
      (-15%) were significantly decreased. In addition, [(35)S]t
      butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the
      frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%)
      following chronic PCP treatment, while no changes were observed following acute
      PCP treatment. These results indicate that single and repeated administrations of
      PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD)
      receptor subunits mRNA and its receptor binding in the brain.

PMID- 10941141
TI  - Ventral pallidal injections of a mu antagonist block the development of
      behavioral sensitization to systemic morphine.
AB  - Acute activation of opioid receptors in the ventral pallidum increases motor
      behaviors in rats. The present study was designed to investigate the possibility
      that the ventral pallidum influences motor responses induced by chronic opiate
      treatments and to examine the receptors that may be involved in such an effect.
      For five consecutive days, ambulations were quantified after rats received once
      daily intraperitoneal (i.p.) injections of morphine (10 mg/kg) or saline
      following bilateral intra-ventral pallidal injections of either saline (0.5
      microl/hemisphere), the mu antagonist CTOP (2. 1 microg/0.5microl/hemisphere), or
      the D1 antagonist SCH23390 (0.25 microg/0.5microl/hemisphere). Behavioral
      sensitization to an acute morphine challenge (10 mg/kg i.p.) was assessed 72 h
      after terminating the repeated treatment regimen. Rats who repeatedly received
      the intra-ventral pallidal saline + i.p. morphine exhibited increases in
      ambulations during the chronic treatment protocol and this effect was greatly
      enhanced (i.e., sensitized) following the post withdrawal acute morphine
      challenge. Rats repeatedly treated with intra-ventral pallidal CTOP + i.p.
      morphine did not display a motor response either during the chronic treatment
      regime or to the acute morphine challenge; an effect not seen when CTOP was
      injected into brain structures located dorsal to the ventral pallidum. The rats
      repeatedly treated with intra-ventral pallidal injections of SCH23390 + i.p.
      morphine demonstrated a motor response during the chronic protocol but the
      magnitude of this response was not significantly enhanced by the acute morphine
      challenge. These results demonstrate that: 1) mu opioid and D1-like dopamine
      receptors in the ventral pallidum influence the increase in locomotion that
      occurs during repeated morphine treatments; and 2) mu opioid (but not D1)
      receptors in the ventral pallidum are important in the postwithdrawal sensitized
      response to morphine. Such observations indicate that the ventral pallidum plays
      a critical role in morphine-induced behavioral sensitization.

PMID- 10941142
TI  - Quantitation of striatal and extrastriatal D-2 dopamine receptors using PET
      imaging of [(18)F]fallypride in nonhuman primates.
AB  - [(18)F]Fallypride is a highly selective, high-affinity dopamine D-2 receptor
      ligand. The high affinity, K(D) = 30 pM, makes it a suitable candidate for
      visualizing both striatal and extrastriatal binding in the brain. In this work,
      dynamic PET studies of two macaque monkeys were acquired along with arterial
      plasma samples. Compartmental analysis and Logan plots were used to analyze the
      striatum, thalamus, frontal, and temporal cortices and to validate a reference
      region of analysis which yields a distribution volume ratio (DVR). The cerebellum
      was used as the reference region. The results indicate that all methods of
      analysis are in close agreement over all the analyzed regions in the brain. The
      average DVRs for the two monkeys was found to be: caudate = 26, putamen = 29,
      thalamus = 3.8, frontal ctx = 1.7, and temporal ctx = 1.7 on a high-resolution
      PET scanner. It was found that a scan time of 2 h is needed to accurately
      estimate the DVR for all regions of the brain. The striatal regions require the
      longest to linearize and are the most sensitive to variations in the average
      tissue-to-plasma efflux constant, k(2). For the extrastriatal regions, the effect
      of the k(2) term on DVR calculation is negligible. Repeatability measurements for
      all regions were found to be within 10% using the DVR parameter.

PMID- 10941143
TI  - Effects of crus cerebri lesions and repeated amphetamine treatment on the
      activity of nigral dopaminergic neurons.
AB  - Previous research suggests that the firing rate of dopamine (DA) neurons in the
      substantia nigra pars compacta (SNC) may be altered by repeated DA agonist
      treatment. Because changes in the frequency of DA activity could reflect the
      firing patterns (e.g., bursting) of the neurons sampled, this study examined both
      the firing rate and pattern of SNC DA neurons after long-term amphetamine (AMPH)
      treatment (5 mg/kg d-AMPH s.c. twice daily for 6 days). To assess the
      contribution of postsynaptic feedback from the forebrain, unilateral electrolytic
      lesions were made to the crus cerebri (CC), containing the striatonigral pathway,
      prior to AMPH treatment. Single-unit activity of presumed SNC DA neurons was
      recorded in adult male rats under urethane anesthesia. Spontaneous firing rate
      was reduced by AMPH treatment, relative to saline vehicle, but was unaffected by
      CC or sham lesions. Neurons categorized as bursting had faster rates of activity
      than nonbursting cells. AMPH treatment reduced the number of bursts seen in
      intact rats but increased bursting in lesioned rats. These results suggest that
      changes in DA firing rate previously found after chronic AMPH may reflect altered
      patterns of activity. In addition, the effects of long-term AMPH on the firing
      patterns of DA neurons appear to be mediated by fibers in the CC.

PMID- 10941144
TI  - Positron emission tomography of radioligand binding in porcine striatum in vivo:
      haloperidol inhibition linked to endogenous ligand release.
AB  - The ligands N-methylspiperone and haloperidol both bind to D(2)-like dopamine
      receptors. The competitive nature of the binding over a wide range of haloperidol
      concentrations and the effect on dopamine release have never been tested in vivo.
      We determined the competitive interaction between 3-N-[(11)C]methylspiperone
      ([(11)C]NMSP) and haloperidol binding to striatal dopamine D(2)-like receptors
      with positron emission tomography (PET) of pig brain. [(11)C]NMSP tomography was
      performed with haloperidol at five different plasma concentrations maintained
      constant by programmed infusion. Kinetic parameters of ligand competition for
      binding in the striatum were determined by deconvolving time-activity curves of
      the striatum and cerebellum from metabolite-corrected arterial plasma [(11)C]NMSP
      and haloperidol concentrations. Two types of [(11)C]NMSP-binding sites were
      evident in the striatum, both saturable by haloperidol administration. The
      preponderant or primary sites bound [(11)C]NMSP irreversibly, as dopamine D2-like
      receptors, while the secondary sites bound [(11)C]NMSP reversibly, as do
      serotonin S2 receptors. Woolf-Hanes plots revealed the predicted approximately
      linear relationships between the binding indices and the haloperidol plasma
      concentration. For the irreversible binding sites, this relationship indicated a
      50% inhibitory concentration of haloperidol of 2 nM in plasma and a maximum
      binding capacity of 64 pmol cm(-3) in striatum. For the reversible binding sites,
      the relationship indicated a 50% inhibitory plasma concentration of haloperidol
      of 1 nM and a maximum binding capacity of 4.5 pmol cm(-3). Second-order
      polynomial Eadie-Hofstee-Scatchard plots were consistent with increased
      competition from an endogenous ligand of the irreversibly binding sites only with
      increasing doses of haloperidol. At the highest haloperidol dose, this
      hypothetical endogenous ligand had risen 6-7-fold. We contend that this reveals
      the release of dopamine by high concentrations of haloperidol.

PMID- 10941145
TI  - Transgenic mice overexpressing truncated trkB neurotrophin receptors in neurons
      have impaired long-term spatial memory but normal hippocampal LTP.

PMID- 10941146
TI  - Regulation of the rat oligodendroglia cell line OLN-93 by antisense transfection
      of butyrylcholinesterase.
AB  - Butyrylcholinesterase (BChE) is a glial cell marker with unknown function. For
      neuroepithelial cells, BChE has been shown to regulate cell division and
      expression of the postmitotic marker acetylcholinesterase (AChE), while similar
      studies are lacking for glial cells. By transducing an antisense-5'BChE cDNA
      expression vector via calcium phosphate precipitation, we have analyzed the
      effect of BChE inhibition on proliferation and differentiation of rat
      oligodendroglia-derived OLN-93 cells. OLN-93 cells were chosen because they are
      highly proliferative, while expressing markers of differentiated oligodendrocytes
      (Richter-Landsberg and Heinrich, 1996). First, we established that OLN-93 cells
      do express BChE protein, albeit chiefly in an inactive state, and that BChE was
      decreased by antisense-5'BChE transfection. Cell proliferation was also strongly
      diminished, protein kinase C (PKCalpha) was upregulated, and expression of
      cytoskeletal and cell surface proteins was altered. In particular,
      immunoreactivities of the intermediate filament proteins vimentin and the cell
      adhesion protein F11 were detected, indicating that BChE-inhibited OLN-93 cells
      have shifted toward an astrocytic phenotype. These data support a role of the
      glia marker BChE in CNS glial cell proliferation and differentiation, achieved
      via a nonenzymatic mechanism. The possible biomedical impact of BChE protein,
      e.g., on CNS nerve regeneration, is briefly discussed.

PMID- 10941147
TI  - Oligodendrocytes in brain and optic nerve express the beta3 subunit isoform of
      Na,K-ATPase.
AB  - The Na,K-ATPase, which catalyzes the active transport of Na(+) and K(+), has two
      principal subunits (alpha and beta) that have several genetically distinct
      isoforms. Most of these isoforms are expressed in the nervous system, but certain
      ones are preferentially expressed in glia and others in neurons. Of the beta
      isoforms, beta1 predominates in neurons and beta2 in astrocytes, although there
      are some exceptions. Here we demonstrate that beta3 is expressed in rat and mouse
      white matter oligodendrocytes. Immunofluorescence microscopy identified beta3 in
      oligodendrocytes of rat brain white matter in typical linear arrays of cell
      bodies between fascicles of axons. The intensity of stain peaked at 20 postnatal
      days. beta3 was identified in cortical oligodendrocytes grown in culture, where
      it was expressed in processes and colocalized with antibody to
      galactocerebroside. In the mouse and rat optic nerve, beta3 stain was seen in
      oligodendrocytes, where it colocalized with carbonic anhydrase II. For
      comparison, optic nerve was stained for the beta1 and beta2 subunits, showing
      distinct patterns of labelling of axons (beta1) and astrocytes (beta2). The C6
      glioma cell line was also found to express the beta3 isoform preferentially.
      Since beta3 was not found at detectable levels in astrocytes, this suggests that
      C6 is closer to oligodendrocytes than astrocytes in the glial cell lineage.

PMID- 10941148
TI  - Prolonged corticosterone treatment of adult rats inhibits the proliferation of
      oligodendrocyte progenitors present throughout white and gray matter regions of
      the brain.
AB  - It is well established that glucocorticoids inhibit the proliferation of
      progenitor cells that occurs in the hippocampal dentate gyrus of adult mammals.
      Active cell proliferation also occurs in the subventricular zone (SVZ) of the
      lateral ventricle and, to a lesser extent, throughout white and gray matter
      regions of the adult brain. The aim of the present study was to determine whether
      extrahippocampal cell proliferation is also affected by glucocorticoids. The cell
      proliferation marker bromodeoxyuridine (BrdU) was administered to control rats,
      to adrenalectomized rats, and to rats treated with a daily injection of
      corticosterone (10 mg/kg) for a period of 15 days. In control and
      adrenalectomized rats, high to low numerical densities of BrdU-labeled nuclei
      were detected within the different forebrain regions examined. In rats treated
      with corticosterone, a dramatic decrease of cell proliferation was detected in
      the dentate gyrus, but also throughout all white and gray matter regions
      examined, except for the SVZ of the lateral ventricle. Double-labeling
      experiments indicated that throughout the different white and gray forebrain
      regions examined, except for the SVZ, BrdU-labeled nuclei were essentially
      associated with cells immunostained for the marker of oligodendrocyte progenitors
      NG2. These data indicate that glucocorticoids inhibit the proliferation of
      oligodendrocyte precursors located throughout the white and gray matter regions
      of the adult rat brain. Since the proliferation of oligodendrocyte precursors
      plays a major role in the processes of remyelination, these data raise the
      question of possible detrimental effects of therapeutic treatments of CNS trauma
      based on the administration of glucocorticoids.

PMID- 10941149
TI  - Areas of demyelination do not attract significant numbers of schwann cells
      transplanted into normal white matter.
AB  - If Schwann cell transplantation is to be used as a therapy for demyelinating
      disease, it is important to know if the number of transplanted cells and their
      transplantation site affects the extent of remyelination. Primary Schwann cell
      cultures were obtained from neonatal rat sciatic nerve, purified, and expanded
      using bovine pituitary extract and forskolin. Areas of persistent demyelination
      were created in the dorsal funiculus of the thoracolumbar spinal cord of rats by
      injecting ethidium bromide into white matter exposed to 40 Gy of X-irradiation,
      and a high and low number of Schwann cells were transplanted, into either the
      area of demyelination or the dorsal funiculus cranial to the area of
      demyelination. Animals were perfused 4 weeks after transplantation. After
      injection of 4 x 10(4) cells into the area of demyelination, the area of Schwann
      cell remyelination was 0.88 +/- 0.16 mm(2), while following the injection of 3 x
      10(3) cells it was significantly smaller, 0.29 +/- 0.09 mm(2). After implantation
      of Schwann cells 1-3 mm (mean 2.5 mm) cranial to the area of demyelination, only
      one of the eight animals (a high-dose animal) showed extensive Schwann cell
      remyelination. In this animal, the cells were transplanted within 1 mm of the
      area of demyelination, well within the length of tissue over which cells are
      passively spread by the injection procedure (1-3 mm). Our results show that
      significant numbers of transplanted Schwann cells are not attracted through
      normal tissue to areas of demyelination and when transplanted into areas of
      demyelination the extent of myelination is related to the number of Schwann cells
      transplanted.

PMID- 10941150
TI  - Thioredoxin reductase and glutathione synthesis is upregulated by t
      butylhydroquinone in cortical astrocytes but not in cortical neurons.
AB  - The electron donors glutathione and thioredoxin play many vital roles in the
      mechanisms of cells to cope with oxidative stress. Critical to such antioxidant
      functions are the ability to synthesize glutathione and keep it reduced via
      glutathione reductase and the ability to reduce oxidized-thioredoxin via
      thioredoxin reductase. The rate-limiting enzyme for glutathione synthesis, gamma
      glutamylcysteine synthase, is regulated by the antioxidant response element,
      whereas little is known about the regulation of expression of the selenoenzyme
      thioredoxin reductase. There were several objectives in this study. One was to
      determine whether the phase II enzyme inducer t-butylhydroquinone would increase
      thioredoxin reductase in neural cells; we found that both cytosolic and
      mitochondrial thioredoxin reductase activity and protein content is increased in
      cortical astrocytes, but not in cortical neurons. A second objective was to
      determine whether there are differences in the ability of t-butylhydroquinone to
      increase glutathione content in astrocytes and neurons; we found that glutathione
      is increased in astrocytes but not neurons. Finally, t-butylhydroquinone addition
      did not affect glutathione reductase activity in neurons and caused only a modest
      increase in astrocytes. Our findings emphasize the central role that astrocytes
      play in the antioxidant activities of the CNS. Our findings also suggest that
      thioredoxin reductase and gamma-glutamylcysteine synthase belong to the same
      synexpression group.

PMID- 10941151
TI  - Death signaling pathway induced by pyrrolidine dithiocarbamate-Cu(2+) complex in
      the cultured rat cortical astrocytes.
AB  - The chelating and antioxidant effects of pyrrolidine dithiocarbamate (PDTC) have
      been investigated extensively for preventing cell death induced by different
      insults. However, the toxic effects of PDTC have been studied only recently and
      fewer studies on the toxic effects on astrocytes have been reported. In our
      study, we demonstrated that both PDTC and Cu(2+) alone were rated as only weakly
      toxic in inducing cell death in cortical astrocytes with IC(50) of 300 microM and
      180 microM, respectively. However, PDTC and Cu(2+) in the complex form markedly
      potentiated with each other by about 1,000-fold with IC(50) of 0.3 microM PDTC
      plus 10 microM Cu(2+). Other metals at concentrations of 3-10 microM (VO(4)(5+),
      Cr(6+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Zn(2+), Pb(2+), Bi(2+), Ba(2+), UO(2+),
      Cs(+), SeO(4)(2-), La(3+)) had no such potentiating effects on PDTC. Changes in
      morphology (nuclear condensation), apoptotic body formation, and hypodiploidity
      of DNA suggested that the PDTC-Cu(2+) complex induced cell death through an
      apoptotic process. Further studies showed that the PDTC-Cu(2+) complex decreased
      mitochondrial membrane potential, increased hydrogen peroxide production, and
      depleted GSH contents. After the increased oxidative stress, PDTC-Cu(2+) complex
      differentially activated JNKs, ERK, p38 and caspase 3, which caused PARP
      degradation in a time-dependent manner. All these effects were consistent with
      the increased cellular Cu contents. The nonpermeable copper-specific chelator
      bathocuproine disulfonate (BCPS), but not the permeable Cu(2+) chelator
      neocuproine, abolished all the observed effects. Antioxidants (N-acetylcysteine
      [NAC], vitamin C), catalase, and Cu(2+)-binding proteins (albumin, hemoglobin,
      and higher serum) reduced the cytotoxic effects of PDTC-Cu(2+) complex. We
      concluded that the death signaling pathway of PDTC-Cu(2+) complex was mediated by
      oxidative stress and subsequent JNK activation. These findings imply that PDTC, a
      widely used pesticide and medicine that is capable of penetrating the blood-brain
      barrier, may cause neurotoxicity through astrocyte dysfunction.

PMID- 10941152
TI  - Phagocytosis of neuronal or glial debris by microglial cells: upregulation of MHC
      class II expression and multinuclear giant cell formation in vitro.
AB  - Most CNS pathologies are accompanied by the occurrence of activated, phagocytic
      microglial cells. We intended to investigate whether (1) isolated microglial
      cells removed from the CNS cytokine network sustain their capacity to acquire an
      activated phenotype when challenged with cellular or noncellular debris; and (2)
      different substrates lead to different patterns of microglial activation. It was
      observed that although removed from their usual surroundings microglial cells
      preserve their ability to transform to an amoeboid morphology, form
      multinucleated giant cells, and enhance their expression of MHC class II when
      exposed to membranes of neuronal or glial origin. Furthermore, cellular
      substrates derived from primary hippocampal neuronal cultures, neuroblastic cells
      (B50), or glial cells were all able to induce similar morphological changes and
      enhanced expression of MHC class II. In contrast, phagocytosis of Latex beads
      induced an amoeboid morphology but no increase in the expression of
      immunologically relevant molecules. Interferon-beta (IFN-beta), a substance
      clinically used in the treatment of the relapsing-remitting form of multiple
      sclerosis, was shown to inhibit the phagocytosis-induced upregulation of MHC
      class II. In summary, phagocytic microglial cells are independent from the CNS
      cytokine network in their transition from a resting to an activated phenotype;
      and different cellular substrates, regardless whether they are of neuronal,
      glial, or even malignant origin, result in similar morphological and functional
      changes.

PMID- 10941153
TI  - GFAP null astrocytes are a favorable substrate for neuronal survival and neurite
      growth.
AB  - During the development of the CNS, astrocytes play a key role as a substrate for
      neuronal migration and axonal growth. These neuron-astrocyte interactions could
      be regulated, in part, by the astrocytic cytoskeleton. Nestin, vimentin, and
      glial fibrillary acidic protein (GFAP) are the three identified proteins
      constitutive of intermediate filaments present in astrocytes. In the present
      study, we used mice deficient in GFAP to define the influence of the major
      protein of the astrocytic cytoskeleton on neuron survival and axonal growth in a
      model of neuron-astrocyte coculture. We observed that GFAP null astrocytes are a
      better substrate for neuronal survival and neurite outgrowth than wild-type
      astrocytes. This may be correlated with the relatively late occurrence of GFAP
      expression in astrocyte maturation when the early steps of neurogenesis are
      completed.

PMID- 10941154
TI  - High-dose intra-arterial cisplatin and concurrent hyperfractionated radiation
      therapy in patients with locally advanced primary squamous cell carcinoma of the
      head and neck: report of a phase II study.
AB  - BACKGROUND: This phase II study evaluates the tolerability and efficacy of
      concurrent hyperfractionated radiation therapy (HFX-RT) and high-dose intra
      arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma
      of the head and neck (SCCHN). METHODS: Between December 1995 and November 1997,
      20 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8-79.2
      Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150 mg/m(2) given at
      the start of RT boost treatment [start of week 6]). Seventeen patients (85%) had
      T4 disease, and 14 (70%) had N2/ N3 disease. RESULTS: Grade 3-5 acute toxicity
      was limited to one grade 4 (5%) and 14 grade 3 (70%) mucosal events. No grade 3/4
      hematologic toxicity was observed. Median weight loss during therapy was 9%
      (range, 2%-16%). Eighteen patients had complete response (90%) at the primary
      site; 14 were confirmed pathologically. Among 17 patients with positive neck
      disease, 16 (94%) achieved complete response in the neck, including 12 of 13
      patients with N2/N3 disease who underwent planned neck dissection. Active follow
      up ranges from 12 to 32 months (median, 20 months) with 11 patients alive without
      disease, 5 dead of disease, and 4 dead of intercurrent disease. Eighteen patients
      (90%) remained disease free at the primary site, and the locoregional control
      rate is 80%. CONCLUSIONS: High-dose IA cisplatin and concurrent HFX-RT as used in
      this study is feasible and warrants further investigation. The high complete
      response rate and low grade 4 toxicity in this highly unfavorable subset of
      patients appears better than previously reported chemoradiation regimens for more
      favorable patients.

PMID- 10941155
TI  - Esthesioneuroblastoma: the Johns Hopkins experience.
AB  - BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon malignant neoplasm of the
      upper nasal cavity. Therapeutic management approaches for this neoplasm lack
      uniformity and there is no universally accepted staging system. METHODS: A
      retrospective review of 27 patients with histologically confirmed ENB managed at
      The Johns Hopkins Hospital. RESULTS: Eighty-five percent of patients had surgical
      resection as part of their disease management. Complete surgical resection was
      achieved in 62% of patients who had a craniofacial resection. Eighty percent of
      patients with negative surgical margins remain with no evidence of disease, with
      a median follow-up of 5.6 years. Adjuvant radiation therapy was beneficial to 62%
      of patients with positive surgical margins. Clinical responses were observed with
      cisplatin- and etoposide-containing chemotherapy regimens in patients with
      advanced disease. A revised staging system based on our experience is proposed.
      CONCLUSIONS: ENB is best managed by craniofacial resection with complete tumor
      resection. Adjuvant radiation therapy is warranted in patients that remain with
      positive histologic margins of resection. Chemotherapy with cisplatin- and
      etoposide-containing regimens may be useful for palliation of advanced disease.

PMID- 10941156
TI  - Positive surgical margins in neck dissection specimens in patients with head and
      neck squamous cell carcinoma and the effect of radiotherapy.
AB  - BACKGROUND: To evaluate the outcome after surgery and radiotherapy for extensive
      nodal disease in patients with primary head and neck cancer. METHODS: Between
      1973 and 1995, 77 from a total of 1398 patients had histopathologic evidence of
      positive margins in 85 neck dissection specimens for squamous cell carcinoma of
      the oral cavity, oropharynx, larynx, or hypopharynx. Postoperative radiotherapy
      with a curative dose was given to 50 necks. Ipsilateral neck recurrence was
      defined as the relevant event, and cumulative survival distributions were
      estimated by the Kaplan-Meier method. Differences between groups were analyzed
      with the log rank test. RESULTS: Disease-free survival was 24.9% at 2 years, and
      disease-specific survival was 33.6% at 2 years. After restriction of the 50
      patients who received postoperative curative radiotherapy, the time to neck
      recurrence was stratified according to irradiation dosage, with 62.5 Gy as the
      cutoff point. A statistically significant difference was found for patients
      treated with 62.5 Gy or more, with a regional control rate of 75.6% at 2 years (p
      <.036). CONCLUSIONS: The overall outcome after neck dissection with positive
      surgical margins is poor. Considerable improvement is achieved by postoperative
      radiotherapy treatment with dosages of 62.5 Gy or more.

PMID- 10941157
TI  - Neck lymph node metastases to the posterior triangle apex: evaluation of clinical
      and histopathological risk factors.
AB  - BACKGROUND: Dissection of posterior triangle apex (APEX) is a surgical step in
      supraomohyoid and lateral neck dissections. The prevalence of lymphatic
      metastases at this site and the clinicohistopathologic conditions that influence
      their occurrence have not been established. We have evaluated the prevalence and
      the risk factors for cervical metastases in lymph nodes of the APEX. METHODS:
      Sixty-two neck dissections were performed in 51 patients with squamous cell
      carcinoma of the oropharynx, hypopharynx, oral cavity, glottic larynx, and
      supraglottic larynx or with primary occult tumor. We correlated the presence of
      positive metastases in the APEX with the neck level involved either clinically
      (CLIN) or histopathologically (H/P) and with the number of CLIN- or H/P-positive
      neck levels with metastases. The prevalence of metastases in the APEX in elective
      (N0) and therapeutic (N+) neck dissections was also compared. This prevalence was
      also compared with that for each neck level. The histopathologic comparisons
      between the APEX and the neck levels were calculated for N0, N+, and all neck
      dissections. The primary site of tumor was correlated with the presence of H/P
      positive nodes in the APEX. RESULTS: The overall prevalence of lymphatic
      metastases in the APEX was 6.5%. The prevalence in N0 neck dissections was 2.3%
      and in N+ neck dissections it was 16.7%. The prevalence of lymphatic metastases
      in the APEX for primary tumors of pharynx was 23.1%, for the oral cavity it was
      3.6%, and it was 0% for other sites. Metastases in the APEX were not influenced
      by the neck level with CLIN or H/P metastases in N+ necks. The number of CLIN- or
      H/P-positive neck levels had no influence on histopathologic metastases in the
      APEX. Factors that influenced metastases in the APEX were positive
      histopathologic metastases at level II for N0 neck dissections and positive
      histopathologic metastases at level II or III for all neck dissections. All the
      comparisons were analyzed using Fisher's or Poisson's test. CONCLUSIONS: The
      prevalence of histopathologic metastases in the APEX in N+ necks is 7.3 times
      greater than that of N0 necks and for primary tumors of pharynx it was 6.4 times
      greater than for the oral cavity and significantly greater than for the larynx.
      Histopathologic metastases at level II for clinically N0 necks and
      histopathologic metastases to level II or III for all neck dissections are risk
      factors for metastases in the APEX. The number of positive levels did not
      influence the prevalence of metastases in the APEX. There are no isolated
      metastases in the APEX of the posterior triangle.

PMID- 10941158
TI  - The submental island flap in head and neck reconstruction.
AB  - BACKGROUND: The submental island flap (SIF) is a new alternative in the
      reconstruction of various head and neck defects. We present our preliminary
      experience in the use of this flap and describe the surgical technique. METHODS:
      Nine patients underwent reconstruction with the SIF between January 1998 and July
      1999. The SIF has been used for the reconstruction of the cervical esophageal
      stenosis in 2 patients, floor of mouth and tongue defects in 6 patients, and a
      hemilaryngectomy defect in 1 patient. RESULTS: With the exception of one partial
      flap loss caused by arterial insufficiency, no flap failures were observed. All
      the donor site defects but one were closed primarily. One patient who underwent
      reconstruction of a hemilaryngectomy defect underwent revision surgery because of
      intractable hair growth on the transferred skin paddle. Marginal mandibular nerve
      function was intact in all the cases. CONCLUSIONS: When combined with the
      reported experience of other surgeons, our preliminary experience showed that the
      SIF was an excellent alternative in the reconstruction of head and neck defects
      because of its reliability, versatility, and relative ease of application.

PMID- 10941159
TI  - The effects of conjugated deferoxamine in porcine skin flaps.
AB  - BACKGROUND: The free radical scavenger, deferoxamine (DFO) has been shown to
      reduce skin flap necrosis; however, its shortcomings are its toxicity and short
      plasma half-life. METHODS: This study investigates the effects of the less toxic,
      longer acting conjugated form, DFO-Hespan (DFO-H), to ischemic porcine skin
      flaps. During the study, DFO-H plasma concentrations and flap viability were
      evaluated over 10 days. RESULTS: Steady DFO serum levels were maintained with no
      evidence of systemic side effects. However, DFO-H was not effective in increasing
      porcine skin flap viability. Mean treated flap viability (n = 18) was 36.2% +/-
      1.7% (mean +/- SE ) vs control (n = 16) 35.8% +/- 2.6%, p =.9. CONCLUSION: DFO-H
      conjugation increases its half-life and its systemic tolerance for DFO. However,
      this conjugation may also reduce DFO's effectiveness to preserve flap survival
      probably by decreasing its ability to reach the intracellular oxygen free
      radicals. In addition, further studies are needed to investigate whether longer
      DFO administration given postoperatively can be more effective in reducing
      ischemic injury.

PMID- 10941160
TI  - Chromosome 22q a frequent site of allele loss in head and neck carcinoma.
AB  - BACKGROUND: Loss of heterozygosity (LOH) correlates with inactivated tumor
      suppressor genes. LOH at chromosome arm 22q has been found in a variety of human
      neoplasms, suggesting that this region contains a tumor suppressor gene(s) other
      than NF2 important to tumorigenesis. The aim of this study was to evaluate the
      presence of LOH on chromosome 22q11.2-13 and determine whether there was a
      relationship between loss in this genomic region and tumor histologic parameters,
      anatomic site, and survival in patients with squamous cell carcinoma of the head
      and neck (HNSCC). METHODS: Fifty matched blood and HNSCC tumor samples taken at
      the time of surgical treatment were evaluated for LOH by use of four
      microsatellite markers mapping to 22q11.2-q13. Clinical information was available
      for all patients. The frequency and distribution of LOH was correlated with
      clinical (age, sex, use of tobacco and alcohol, site of primary tumor, clinical
      stage, adjuvant therapy and overall survival) and histologic parameters
      (histopathologic stage, tumor differentiation). RESULTS: LOH at 22q was found in
      19 of 50 (38%) informative tumors. The respective incidence of allelic loss for
      the patients was as follows: 28% at D22S421, 10% at D22S277, 8% at D22S446, and
      4% at D22S280. No statistical differences were apparent with a mean follow-up of
      30 months. Laryngeal tumors showed a higher incidence of LOH compared with oral
      tumors. CONCLUSIONS: These results suggest that the D22S277 locus may be closely
      linked to a tumor suppressor gene (TSG) and involved in upper aerodigestive tract
      carcinogenesis. In particular, laryngeal tumors may harbor another putative TSG
      on 22q11.2-q12.3 that may play a role in aggressive stage III/IV disease.

PMID- 10941161
TI  - The relationship between genetic susceptibility to head and neck cancer with the
      expression of common fragile sites.
AB  - BACKGROUND: Numerous studies have recently been conducted to investigate genetic
      mechanisms in cancer causes and pathogenesis. Some of these studies have shown
      that there were certain specific chromosomal defects in normal cells of cancer
      patients and in their first-degree relatives. It was suggested that these
      individuals were susceptible to cancer development when compared with people
      without these defects. Materials and Methods Chromosomal anomalies, such as gaps,
      breaks, and acentric fragments, and fragile site expression rates were determined
      in peripheral blood lymphocyte cultures in 14 head and neck cancer patients, 17
      first-degree relatives of these patients, and 20 healthy individuals as a control
      group in this study. RPMI 1640 medium, composed of aphidicolin, 5
      bromodeoxyuridine, and caffeine were used for the induction of fragile sites.
      RESULTS: In cytogenetic and statistical evaluation, it was observed that both
      chromosomal aberration rates and fragile site expression frequencies in head and
      neck cancer patients and in their first-degree relatives were significantly
      greater than the control group (p <.05). It was found that fragile site
      expression was site specific in head and neck cancer patients and in their first
      degree relatives. These specific sites were determined to be 1p21-22, 1q21, 1q25,
      2q21, 2q31-33, 3p14, 16q22-23, 18q21, and 22q12 sites. CONCLUSIONS: These
      findings support studies showing that the fragile sites might be unstable factors
      in human genomes and their expression could be affected by some genetic factors,
      such as tumor suppressor genes and mismatch repair genes, and by some
      environmental factors, such as benzo (a) pyrene, dimethylnitrosamine, and
      dimethylsulfate. In conclusion, fragile sites may be playing an important role in
      the genetic tendency to head and neck cancer. Overexpression of these sites in
      normal lymphocytes may be used as a reliable marker to determine the genetic
      susceptibility in head and neck cancer patients and in their first-degree
      relatives.

PMID- 10941162
TI  - Prognostic value of c-erbB2 and other markers in patients treated with
      chemotherapy for recurrent head and neck cancer.
AB  - BACKGROUND: Chemotherapy is widely used in patients with recurrent head and neck
      cancer, but no clear markers are available that can predict response to treatment
      or survival in these patients. METHODS: Twenty-nine patients evaluated in this
      study had recurrent head and neck squamous carcinomas, previously treated with
      surgery and/or radiotherapy. Patients received either cisplatin and 5
      fluorouracil (5-FU) (n = 15) or cisplatin and paclitaxel (Taxol) (n = 14).
      Expression of c-erbB2, p53, glutathione S-transferase pi, multidrug resistance
      associated protein, thymidylate synthase, and glutathione synthetase were
      evaluated in biopsy tissues. RESULTS: Response to chemotherapy was significantly
      correlated with improved survival (progression-free survival, p =.0005; overall
      survival, p =. 007). Of the factors examined, expression of c-erbB2 was
      associated with significantly decreased progression-free survival (p =.023) and
      overall survival (p =.029). This was seen in patients treated with
      cisplatin/taxol but not in patients treated with cisplatin/5-FU. CONCLUSION:
      Expression of c-erbB2 may be a clinically useful predictor of survival in this
      group of patients.

PMID- 10941163
TI  - Genetic polymorphisms in head and neck cancer risk.
AB  - OBJECTIVE: To assess whether genetic polymorphisms implicated as risk factors for
      other tobacco-associated malignancies are associated with altered risk of head
      and neck squamous cell carcinoma. DESIGN: Case-control study. SUBJECTS: One
      hundred sixty patients with head and neck squamous cell carcinoma recruited from
      a university-based head and neck oncology clinic and 149 population-based
      controls. METHODS: Genotyping of the CYP1A1 (Ile462Val), GSTM1 (null), GSTP1
      (Ile105Val), GSTT1 (null), and P53 (Arg72Pro) genes was performed by polymerase
      chain reaction-based techniques on DNA prepared from peripheral blood. In
      addition, a questionnaire was used to collect demographic information from each
      subject. RESULTS: Cases were significantly older (p <.0001) and had significantly
      greater tobacco use (p <.0001) and were more likely to be male (p <.0001) than
      were control subjects, thus confirming known risk factors for this disease. When
      cases and controls were compared by simple chi-square analysis, only the
      frequency of CYP1A1 (Ile462Val) polymorphism was significantly different between
      cases and controls (OR =.42; 95% CI =.18-.99; p <.04). However, with a logistic
      regression model to control for known risk factors, we were unable to demonstrate
      a significant association with head and neck cancer for any of the polymorphisms
      tested, including CYP1A1. CONCLUSIONS: This population fails to identify a
      relationship between the above-mentioned polymorphisms and head and neck cancer.

PMID- 10941164
TI  - Radio-guided surgery in recurrent renal hyperparathyroidism: report of a case.
AB  - BACKGROUND: It has been demonstrated that radio-guided surgery offers several
      advantages in treating primary hyperparathyroidism. Even if it is considered less
      helpful in renal hyperparathyroidism, it could be of tremendous advantage in the
      treatment of persistent or recurrent secondary hyperparathyroidism. METHODS: We
      report a case of recurrent secondary hyperparathyroidism treated by the use of
      radio-guided surgery. The preoperative assessment consisting of ultrasonography,
      magnetic resonance imaging, and 99mTc-sestamibi scintigraphy identified a
      parathyroid in the upper mediastinum. The patient underwent a radio-guided neck
      re-exploration that allowed a rapid localization and excision of the ectopic
      gland, which was located in the anterosuperior mediastinum, in front of the
      trachea, between the innominant and the left common carotid artery. RESULTS: The
      operative time was 45 minutes. The patient was discharged on the first
      postoperative day. A decrease in serum calcium and parathyroid hormone was
      observed subsequently. A follow-up of 6 months did not show any recurrence.
      CONCLUSIONS: The case reported indicates that radio-guided surgery can help
      surgeons detect parathyroid tissue in selected cases of renal
      hyperparathyroidism.

PMID- 10941165
TI  - Paraganglioma of the thyroid: two cases that clarify and expand the clinical
      spectrum.
AB  - BACKGROUND: Paragangliomas (PGs) can, on rare occasions, arise within the thyroid
      parenchyma presumably from displaced laryngeal paraganglia. On the basis of a
      limited number of reported cases, thyroid PGs invariably affect women, they are
      always benign, and they are usually mistaken for some other more common thyroid
      lesion. METHODS: We describe the histopathologic features, immunohistochemical
      findings, and clinical characteristics of two thyroid PGs. RESULTS: One tumor was
      incidentally discovered in a 55-year-old man during evaluation of a carotid
      bruit. The other tumor aggressively invaded the trachea and esophagus of a 52
      year-old woman with a presumed long-standing nodular goiter. In both cases, the
      initial pathologic evaluation suggested medullary thyroid carcinoma. Both
      patients are alive without recurrent disease after surgical resection.
      CONCLUSIONS: These cases emphasize the need to consider PG in the differential
      diagnosis of neuroendocrine thyroid tumors, even in those tumors involving men or
      behaving in a locally aggressive fashion. Failure to do so carries grave
      implications regarding patient prognosis and management.

PMID- 10941166
TI  - Stratification of stage IV SCC of the oropharynx.

PMID- 10941167
TI  - Overcoming the transclavicular approach: the transmanubrial approach to the
      thoracic inlet.

PMID- 10941168
TI  - Introduction: what do we owe to the frog's eye in retinal research? A historical
      perspective.

PMID- 10941169
TI  - Photoreceptor cells in the Xenopus retina.
AB  - This review summarizes our present state of knowledge about spectrally different
      photoreceptor cell types in the Xenopus retina. The classification of the
      photoreceptors was based on morphology, combined with immunolabelling with
      various anti-visual pigment antibodies and other molecular probes on semithin
      sections and retinal wholemounts. The majority of photoreceptors is represented
      by rods. Altogether 97-98% of the total rod population consists of the principal
      ("red") rods that are selectively labeled by N-terminal specific anti-bovine
      rhodopsin monoclonal antibodies (mAbs) and are maximally sensitive to green
      light. The other, rare, blue-sensitive rod type ("green rod") is thinner, not
      stained by these antibodies but binds C-terminal specific anti-rhodopsin mAbs.
      The major representatives of the cones are red-sensitive and consist of a
      morphologically heterogeneous group comprising both (principal and accessory)
      members of double cones, as well as large single cones. Outer segments in this
      group are selectively labeled by mAb COS-1, specific to the L/M group of cone
      visual pigments. Another, relatively rare cone type is similar in size, but
      slightly smaller than the large single cone and is not labeled by mAb COS-1. This
      cone type is assumed to have a blue-sensitive cone visual pigment. The third,
      least abundant, and immunocytochemically distinct cone type is a small single
      (miniature) cone, which binds mAb OS-2 relatively strongly, and anti-rhodopsin
      mAbs 4B4 and 1D4 weakly. By exclusion, this small single cone may be identical
      with the UV-sensitive cone. Further studies are needed, however, to identify the
      color sensitivity of the latter two cone types.

PMID- 10941170
TI  - Photoreceptor classes and transmission at the photoreceptor synapse in the retina
      of the clawed frog, Xenopus laevis.
AB  - The photoreceptor population in Xenopus consists of a green-sensitive rod
      (lambda(max) = 523 nm), a blue-sensitive rod (lambda(max) = 445 nm) and three
      classes of cone. The largest cone is red-sensitive (lambda(max) = 611 nm). The
      intermediate cone is presumed to be blue-sensitive based on physiological
      criteria, whereas the miniature cone may be UV-sensitive. Horizontal cells (HC)
      are of two sorts: axon-bearing and axonless. The axon-bearing HC is of the
      luminosity type and probably contacts all types of photoreceptor. The axonless HC
      is of the chromaticity type and contacts only intermediate (blue) cones and at
      least one type of rod. During development dendrites of HCs and bipolar neurons
      penetrate photoreceptor bases. A progressive maturation of HC and bipolar
      synapses with rods and cones occurs between tadpoles stages 37/8 and 46.
      Neighboring rods and cones are joined by gap junctions. During this same period,
      the outer segments are laid down and photopigments synthesized. A linear relation
      was found between the quantum capturing ability of the rod and its absolute
      threshold. Mature rods of the Xenopus retina release glutamate in a calcium
      dependent manner. Glutamate release was found to be a linear function of calcium
      influx through L-type calcium channels. Both types of HC possess ionotropic
      glutamate receptors of the AMPA subtype.

PMID- 10941172
TI  - Symphony of rhythms in the Xenopus laevis retina.
AB  - The photoreceptor layer in the retina of Xenopus laevis harbors a circadian
      clock. Many molecular components known to drive the molecular clock in other
      organisms have been identified in Xenopus, such as XClock, Xper2, and Xcrys,
      demonstrating phylogenetic conservation. This model system displays a wide array
      of rhythms, including melatonin release, ERG rhythms, and retinomotor movements,
      suggesting that the ocular clock is important for proper retinal function. A flow
      through culture system allows measurements of retinal rhythms such as melatonin
      release in vitro over time from a single eyecup. This system is suited for
      pharmacological perturbations of the clock, and has led to important observations
      regarding the circadian control of melatonin release, the roles of light and
      dopamine as entraining agents, and the circadian mechanisms regulating
      retinomotor movements. The development of a transgenic technique in Xenopus
      allows precise and reliable molecular perturbations. Since it is possible to
      follow rhythms in eyecups obtained from adults or tadpoles, the combination of
      the flow-through culture system and the transgenic technique leads to the fast
      generation of transgenic tadpoles to monitor the effects of molecular
      perturbations on the clock.

PMID- 10941173
TI  - Amacrine cells of the anuran retina: morphology, chemical neuroanatomy, and
      physiology.
AB  - Amacrine cells are third-order retinal interneurons, projecting their processes
      into the inner plexiform layer. Historically, they were not considered as neurons
      first. By the middle of the 20th century, their neuronal nature was confirmed,
      and their enormous diversity established. Amacrine cells have been most
      successfully subdivided into morphological categories based on two parameters:
      diameter of the dendritic field and ramification pattern in the inner plexiform
      layer. Works combining anatomy, physiology, and neurochemistry are scarce and in
      the case of the anuran retina, the situation is even worse. Correlation between
      morphology, neurochemistry, and physiology is little studied. Here we try to
      build up a database and pinpoint some of the missing data. Obtaining those could
      help to better understand retinal function. Sporadic attempts did not make it
      possible to develop a comprehensive catalog of morphologically distinct amacrine
      cell types in the anuran retina. The number of morphologically identified
      amacrine cells currently stands at 16. The list of neurochemically identified
      distinct cell types can be given as follows: five types GABA-containing cell
      types with secondary markers and at least one without; two glycinergic cell types
      and one interplexiform cell where glycine colocalizes with somatostatin; one
      dopaminergic amacrine cell and also a variant of this with interplexiform
      morphology; two types of serotoninergic cells; three NADPHdiaphorase-positive
      cells, one substance P-positive cell type without identified second marker; one
      CCK-positive cell type without identified second marker and the calbindin
      positive cells (at least one but potentially more types). This adds up to 19 cell
      types, out of which two are interplexiform in character. This is more than that
      could be identified by purely morphological means. Out of Cajal's original 13
      amacrine cell types described in the frog retina, 5 parallel unequivocally with
      neurons defined by neurochemistry. Three others have one close match each, but
      their exact identity is uncertain. The remaining amacrine cells have more than
      one potential matches. At the same time, on one hand the amacrine cell named two
      layered by Cajal so far has no match among the neurochemically identified
      amacrine cells. On the other hand, the interplexiform subtype of the dopaminergic
      cell, the somatostatin-containing glycinergic interplexiform cell, the starburst
      cell, and the bistratified neuropeptide Y-immunoreactive cell have no match among
      Cajal's cells. All in all, the number of known amacrine and interplexiform cells
      now stands at at least 21 in the anuran retina. Physiological characterization of
      amacrine cells shows that their general features seem to be rather similar to
      those described in tiger salamander retina. In Xenopus retina, morphologically
      and physiologically identified amacrine cells responded to light stimulation most
      frequently with ON-OFF characteristics. Immunhistochemical identification of the
      recorded and dye injected cells showed that amacrine cells of the "same
      physiological type" might have different morphology. In other words, amacrine
      cells with different morphology can respond similarly to illumination. Even so,
      small differences between almost identical responses may reflect that the cell
      they stem from indeed belongs to different cell types.

PMID- 10941171
TI  - Mesopic state: cellular mechanisms involved in pre- and post-synaptic mixing of
      rod and cone signals.
AB  - At least twice daily our retinas move between a light adapted, cone-dominated
      (photopic) state and a dark-adapted, color-blind and highly light-sensitive rod
      dominated (scotopic) state. In between is a rather ill-defined transitional state
      called the mesopic state in which retinal circuits express both rod and cone
      signals. The mesopic state is characterized by its dynamic and fluid nature: the
      rod and cone signals flowing through retinal networks are continually changing.
      Consequently, in the mesopic state the retinal output to the brain contained in
      the firing patterns of the ganglion cells consists of information derived from
      both rod and cone signals. Morphology, physiology, and psychophysics all
      contributed to an understanding that the two systems are not independent but
      interact extensively via both pooling and mutual inhibition. This review lays
      down a rationale for such rod-cone interactions in the vertebrate retinas. It
      suggests that the important functional role of rod-cone interactions is that they
      shorten the duration of the mesopic state. As a result, the retina is maintained
      in either in the (rod-dominated) high sensitivity photon counting mode or in the
      second mode, which emphasizes temporal transients and spatial resolution (the
      cone-dominated photopic state). Experimental evidence for pre- and postsynaptic
      mixing of rod and cone signals in the retina of the clawed frog, Xenopus, is
      shown together with the preeminent neuromodulatory role of both light and
      dopamine in controlling interactions between rod and cone signals. Dopamine is
      shown to be both necessary and sufficient to mediate light adaptation in the
      amphibian retina.

PMID- 10941174
TI  - Muller glial cells in anuran retina.
AB  - Whereas in the brain, the activity of the neurons is supported by several types
      of glial cells such as astrocytes, oligodendrocytes, and ependymal cells, the
      retina (evolving from the brain during ontogenesis) contains only one type of
      macroglial cell, the Muller (radial glial) cells, in most vertebrates including
      the anurans. These cells span the entire thickness of the tissue, and thereby
      contact and ensheath virtually every type of neuronal cell body and process. This
      intimate topographical relationship is reflected by a multitude of functional
      interactions between retinal neurons and Muller glial cells. Muller cells are the
      principal stores of retinal glycogen, and are thought to fuel retinal neurons
      with substrate (lactate/pyruvate) for their oxidative metabolism. Furthermore,
      Muller cells are involved in the control and homeostasis of many constituents of
      the extracellular space, such as potassium and perhaps other ions, signaling
      molecules, and of the extracellular pH. They also seem to play important roles in
      recycling mechanisms of photopigment molecules and neurotransmitter molecules
      such as glutamate and GABA. By containing the main retinal stores of glutathione,
      Muller cells may protect retinal neurons against free radicals. Moreover, Muller
      cells express receptors for many neuroactive substances, and may also release
      such substances to their neighbouring neurons. Thus, Muller cells exert many
      functions crucial for signal processing in the normal retina. Moreover, Muller
      cells change their properties in cases of retinal disease and injury, and may
      either support the survival of neuronal cells or accelerate the progress of
      neuronal degeneration.

PMID- 10941175
TI  - Synaptology of the inner plexiform layer in the anuran retina.
AB  - The inner plexiform layer of the retina is a synaptic layer mostly devoid of
      perikarya. It contains the processes of three major neuron types: the bipolar
      cells, which carry information from the photoreceptors, the ganglion cells, which
      are the output elements of the retina, and the amacrine cells, which are able to
      influence the communication between the former two. Since amacrine cells are the
      most diverse retinal neurons, they are in a position to carve out and delineate
      the neural circuits of the inner retina. The aim of this review is to offer a
      summary of findings related to the general synaptology of the inner retina in
      frogs and also to provide some insight into the synaptic organization of
      neurochemically identified amacrine cells. The main conclusions of this paper are
      as follows: (i) Most contacts are formed between amacrine cells. (2) Direct
      bipolar to ganglion cell synapses exist, but are rare in the anuran retina. (3)
      All neurochemically identified amacrine cell types receive inputs from bipolar
      cells, but not all of them form reciprocal contacts with bipolar cell axon
      terminals. (4) A major inhibitory transmitter, gamma-aminobutyric acid, is
      involved in more than 50% of the synapses. Since contacts between inhibitory
      elements were often observed, disinhibitory circuits must also play a role in
      retinal information processing. (5) Reciprocal relationship between dopaminergic
      and gamma-aminobutyric acid-containing cells have been confirmed. Similar
      situation was observed in case of serotoninergic and gamma-aminobutyric acid
      positive elements. No contacts were verified between serotoninergic and
      dopaminergic elements. (6) Both monoamine- and neuropeptide-containing amacrine
      cells establish direct contacts with ganglion cell dendrites, providing a
      morphological basis for neuromodulatory influence on the output elements of the
      retina. Unfortunately, only a handful of studies have been carried out to
      identify the synaptic connections between neurochemically identified cells in the
      anuran retina. Double-label studies at the electron microscope level to reveal
      the synaptic relationship of cell populations containing two different
      transmitters/modulators are extremely rare. Further insight into retinal synaptic
      circuitries could be gained with a combination of electrophysiology and
      morphology at the electron microscopic level. These studies must also involve
      identification of the transmitter receptors on identified cell types. Only after
      this step can the function of different synaptic circuitries be better
      approximated.

PMID- 10941176
TI  - Neuromodulation of ligand- and voltage-gated channels in the amphibian retina.
AB  - To understand information processing in the retina, it is important to identify
      and characterize the types of synaptic receptors and intrinsic ion channels in
      retinal neurons. In order to achieve a high degree of adaptability, retinal
      synapses have evolved multiple neuromodulatory mechanisms. Light or modulatory
      agents can alter the efficacies of both electrical and chemical synaptic
      transmission in the retina. Recent studies indicate that interaction of voltage
      gated channels with those activated by neurotransmitters plays a significant role
      in shaping the light-evoked postsynaptic responses of retinal neurons. The fact
      that both types of channels are subject to modulation by multiple second
      messenger-mediated intracellular processes is a clear indicator of the importance
      of neuromodulation in retinal function. The whole-cell patch clamp technique
      provides a means to study mechanisms of regulation of ion channels by controlling
      intracellular as well as the extracellular environment. This review describes the
      experimental evidence, mostly obtained in our laboratory, which indicates the
      important role of Ca-dependent neuromodulatory processes in the regulation of
      signal transmission in the vertical pathway of the amphibian retina.

PMID- 10941177
TI  - Cerebral microvascular architecture in the common tree shrew (Tupaia glis)
      revealed by plastic corrosion casts.
AB  - The vascularization of the cerebrum (cerebral cortex and basal ganglia) in the
      common tree shrew (Tupaia glis) has been studied in detail using vinyl injection
      and vascular corrosion cast/SEM techniques. It is found that the arterial supply
      of the cerebral cortex are from cortical branches of the middle cerebral artery
      (MCA) and of the anterior cerebral artery (ACA). These arteries are in turn
      branches of the internal carotid artery (ICA). In addition, the cerebral cortex
      receives the blood from the cortical branches of the posterior cerebral artery
      (PCA) that originates from the basilar artery (BA). These cortical arteries gives
      rise to rectilinear orientated intracortical arteries that are divided into dense
      capillary networks to supply the cerebral cortex. The capillary networks drain
      the blood into intracortical veins and then into the tributaries of major
      superficial cerebral veins. The basal ganglia (caudate and lentiform nuclei) are
      supplied by central or perforating branches of the ACA and MCA. These central or
      medullary arteries give rise to arterioles that ramify into dense capillary
      plexuses. The venous blood from both nuclei drains into venules and finally into
      the tributaries of internal cerebral veins. It is obvious that on the ventral
      aspect, the diameter of the lateral striate artery (LSA) and of the penetrating
      arterioles from the MCA are much smaller than that of the MCA. These arterioles
      have few side branches while the peripheral branches of the superficial cerebral
      arteries exhibit several series of branches that are gradually reduced in
      diameter before branching into intracortical arteries. This could be one of the
      reasons why the rupture of cerebral arteries in man mostly occurs in the those
      originating from the ventral surface rather than from the dorsolateral surface.

PMID- 10941178
TI  - Localization of soluble major histocompatibility class II-peptide complexes on T
      cell surface.
AB  - Affinity purified major histocompatibility (MHC)-peptide complexes are
      heterodimeric cell surface glycoproteins and are known to recognize antigen
      specific CD4(+) T cell receptors (TCRs). In general, the affinity of MHC-peptide
      complexes to TCRs are considered very low with a K(D) of 5 x 10(-5) M and,
      therefore, stabilization of these complexes on T cell surface was not reported
      earlier. This could be due to (1) incomplete occupancy of MHC molecules with
      antigenic peptides, (2) variability of the binding constant of peptides to MHC
      molecules, (3) presence of endogenously bound peptides in MHC preparations, or
      (4) a combination of these. Using well-characterized HLA-DR2 complex loaded with
      a high affinity immunodominant epitope analog from human myelin basic protein
      (MBP), which shows release of gamma-IFN by specific stimulation of transformed
      human T cell clone (SS8T). The present report demonstrates a method for the
      localization of bound MHC class II-peptide complexes on T cell surface by
      backscatter electron imaging using in-lens Field Emission Scanning Electron
      Microscopy (FESEM). The localization is specific to the complex recognized by the
      TCR on MHC class II (DR2) and MBP peptide restricted human T cells.

PMID- 10941179
TI  - Za Zdorovie! 'To your health!' in Russian.

PMID- 10941180
TI  - Hunting the arbiters of neurodegeneration.

PMID- 10941181
TI  - Making sense of making hair cells.

PMID- 10941182
TI  - New imaging techniques for early diagnosis of Alzheimer's disease.

PMID- 10941183
TI  - Transcriptional dysregulation in Huntington's disease.
AB  - Although the gene responsible for Huntington's disease was discovered in 1993,
      the pathogenic mechanisms by which mutant huntingtin causes neuronal dysfunction
      and death remain unclear. However, increasing evidence suggests that mutant
      huntingtin disrupts the normal transcriptional program of susceptible neurons.
      Thus, transcriptional dysregulation might be an important pathogenic mechanism in
      Huntington's disease.

PMID- 10941184
TI  - KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis of epilepsy: implications
      for therapy.
AB  - In 1998, the discovery of two novel genes KCNQ2 and KCNQ3, mutated in a rare
      inherited form of epilepsy known as benign familial neonatal convulsions, for the
      first time enabled insight into the molecular etiology of a human idiopathic
      generalized epilepsy syndrome. These disease genes encode subunits of neuronal M
      type K+ channels, key regulators of brain excitability. Analogies between benign
      familial neonatal convulsions and other channelopathies of skeletal and cardiac
      muscle, including periodic paralysis, myotonia and the long QT syndrome, provide
      clues about the nature of epilepsy-susceptibility genes and about the fundamental
      basis of epilepsy as an episodic disorder. It now appears that the KCNQ2/KCNQ3 K+
      channels that are mutated in benign familial neonatal convulsions represent an
      important new target for anti-epileptic drugs. In the future, the identification
      of ion channel defects as predisposing factors in the common epilepsies could
      herald a new era of genotype-specific therapies.

PMID- 10941185
TI  - Serine proteases and brain damage - is there a link?
AB  - The protective blood-brain barrier normally allows diffusion of small molecules
      such as oxygen and carbon dioxide, and transport of essential nutrients, but
      excludes large proteins and other blood constituents from the interstitial space
      of the CNS. However, head trauma, stroke, status epilepticus and other
      pathological conditions can all compromise the integrity of this barrier, and
      allow blood proteins as large as albumin to gain access to the extracellular
      spaces that surround neurons and glia. Given their possible entry into brain
      tissue during cerebrovascular insult, the effects of blood-derived proteases such
      as thrombin, tissue plasminogen activator and plasmin in the CNS have come under
      increasing scrutiny. Evidence now supports a role for serine proteases in the
      sequence of events that can lead to glial scarring, edema, seizure and neuronal
      death.

PMID- 10941186
TI  - Cell death, DNA breaks and possible rearrangements: an alternative view.

PMID- 10941187
TI  - Reply

PMID- 10941188
TI  - Confusion between neuronal apoptosis and activation of programmed cell death
      mechanisms in acute necrotic insults.

PMID- 10941189
TI  - Reply

PMID- 10941190
TI  - Negative symptoms: the 'pathology' of motivation and goal-directed behaviour.
AB  - In many neurological and psychiatric disorders, including Alzheimer's disease and
      schizophrenia, symptoms are present that appear to reflect an essential absence
      of normal movement, cognition and emotional states. These negative symptoms might
      reflect fundamental impairments in basic brain mechanisms that underlie goal
      directed behaviour. Knowledge of the pathology and pathophysiology of these
      diseases, combined with evidence from basic science, offers opportunities for
      understanding the neurobiological basis of goal-directed behaviour, particularly
      the interaction between limbic structures and striato-thalamo-cortical circuits.
      The study of patients with negative symptoms also provides opportunities for
      testing cognitive models of goal-directed behaviour, and eventually to map such
      models onto the neurobiology of both normal and abnormal behaviour.

PMID- 10941191
TI  - Linking DNA damage and neurodegeneration.
AB  - Many human pathological conditions with genetic defects in DNA damage responses
      are also characterized by neurological deficits. These neurological deficits can
      manifest themselves during many stages of development, suggesting an important
      role for DNA repair or processing during the development and maintenance of the
      nervous system. Although the molecular neuropathology associated with such
      deficits is largely unknown, many of the responsible gene defects have been
      identified. The current rapid progress in elucidation of molecular details
      following gene identification should provide further insight into the importance
      of DNA processing in nervous system function.

PMID- 10941192
TI  - Coupling of the IP3 receptor/Ca2+ channel with Ca2+ storage proteins
      chromogranins A and B in secretory granules.
AB  - The secretory granules of neuroendocrine cells, which function as an inositol
      (1,4,5)-trisphosphate-sensitive intracellular Ca2+ store, contain both the
      inositol (1,4,5)-trisphosphate receptor/Ca2+ channel and the high-capacity low
      affinity Ca2+ storage proteins, chromogranins A and B. Chromogranins A and B,
      which exist in approximately 2 mm range in the secretory granules, can bind 50
      100 mol of Ca2+/mol with dissociation constants of 2-4 mm. These proteins
      interact directly with the inositol (1,4,5)-trisphosphate receptor/ Ca2+ channel
      at the intragranular pH 5.5, not only changing the conformation of the inositol
      (1,4,5)-trisphosphate receptor/Ca2+ channel but also modulating the channel
      activity. Given the homo- and heterotetrameric existence of both the inositol
      (1,4,5)-trisphosphate receptor/Ca2+ channel and chromogranins A and B, these
      tetrameric proteins appear to interact, thus controlling the intracellular Ca2+
      concentration.

PMID- 10941193
TI  - Clustering of inhibitory neurotransmitter receptors at developing postsynaptic
      sites: the membrane activation model.
AB  - Recent studies indicate an important role of cytoskeleton-associated and lipid
      anchored proteins in the formation of inhibitory postsynaptic membrane
      specializations. Membrane apposition of the tubulin-binding protein gephyrin is
      essential for the recruitment of inhibitory glycine receptors and GABAA receptors
      to developing postsynaptic sites. Newly disclosed interactions between gephyrin,
      exchange factors for G proteins of the Rho and Rac families, the translational
      regulator RAFT1, and actin-binding proteins like profilin might integrate
      activity-dependent and trophic-factor-mediated signals at developing postsynaptic
      sites. A model of inhibitory neurotransmitter receptor clustering, is proposed,
      in which this process is initiated by receptor-driven activation of
      phosphatidylinositol 3-kinase.

PMID- 10941194
TI  - Endogenous morphine.
AB  - It is now well accepted that endogenous morphine is present in animals, both in
      invertebrates and vertebrates. It is a key signaling molecule that plays an
      important role in downregulating physiological responses, such as those in the
      immune system, including immune elements in the CNS. It has been demonstrated
      that a specific mu-opiate-receptor subtype, mu3, mediates these downregulatory
      effects through release of NO. This article examines morphine as an endogenous
      signaling molecule, in terms of its role in neural and immune regulation.

PMID- 10941195
TI  - Tissue engineering designs for the future: new logics, old molecules.

PMID- 10941196
TI  - Osteogenesis coordinated in C3H10T1/2 cells by adipogenesis-dependent BMP-2
      expression system.
AB  - A novel tissue engineering for bone formation has been proposed, to make
      osteoblast differentiation balanced by transfecting the mesenchymal stem cells
      with a gene encoding human bone morphogenetic protein-2 (hBMP-2) under the
      control of adipocyte specific lipoprotein lipase (LPL) promoter. Due to the
      promoter specificity, the initiation of BMP transcription is dependent on
      adipogenesis. For 14-day culture in the presence of ascorbic acid (asc) and beta
      glycerophosphate (gly), nontransfected mouse embryonic fibroblast C3H10T1/2
      (10T1/2) cells showed extensive accumulation of lipid droplets and adipocyte
      specific enzyme glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression, but
      exhibited neither BMP-2 expression, high alkaline phosphatase (ALP) activity
      which reflects osteoblast phenotype. On the other hand, transfected 10T1/2 cells
      showed hBMP-2 expression, high ALP activity and low level of G3PDH. mRNA
      expression accompanied with minimal lipid droplets. These results indicate that
      10T1/2 cells are proved to be differentiated with maintaining coordinated balance
      of adipogenesis and osteogenesis, when they are transfected by the gene encoding
      hBMP-2 under the control of LPL promoter.

PMID- 10941198
TI  - Novel method for the quantitative assessment of cell migration: a study on the
      motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL)
      cells.
AB  - A novel method of quantitating cell migration has been proposed for the potential
      utilization of tissue engineered scaffolds. Applying Alt's conservation law to
      describe the motion of first passage ACL and MCL cells, we have developed a
      quantitative method to assess innate differences in the motility of cells from
      these two ligamentous tissues. In this study, first passage ACL and MCL cells
      were cultured from four mature New Zealand white rabbits. One side of the cell
      monolayer was scraped completely away to create a wound model. The cell moved
      into the cell-free area, and cell density profiles were analyzed at 6 h and 12 h.
      Values of the random motility coefficient (mu) were then estimated by curve
      fitting the 6 h and 12 h data to a mathematical model, derived from the
      conservation law of cell flux. During 6 h of incubation in medium supplemented
      with 1% FBS, MCL cells (mu(MCL) = 4.63 +/- 0.65 X 10(-6) mm(2)/sec) were
      significantly (p < 0.05) more mobile than ACL cells (mu(ACL) = 2.51 +/- 0.31 X
      10(-6) mm(2)/sec). At 12 h, the MCL cells also appeared to move faster (mu(ACL) =
      4.39 +/- 0.63 X 10(-6) mm(2)/sec, mu(MCL) = 6.59 +/- 1.47 X 10(-6) mm(2)/sec),
      but the difference was not statistically significant (p = 0.18). Exposure of the
      cells to growth factors PDGF-BB or bFGF for 6 h had no significant effect on the
      migration of the ACL and MCL cells. However, exposure of the ACL cells (p < 0.05)
      and the MCL cells (p = 0.19) to 1 ng/mL of PDGFBB for 12 h enhanced their
      migration. Incubation with a high concentration (100 ng/mL) of PDGF-BB or bFGF at
      concentrations tested (1 or 100 ng/mL) for 12 h, produced little or no migratory
      stimulation on these ligament cells. Our findings support the previous
      qualitative observations made by numerous investigators. The novel methodology
      developed in this study may provide a basis for tissue engineering, and the
      results may be applied to tissue reconstruction techniques of the knee ligaments.

PMID- 10941199
TI  - Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system.
AB  - Our laboratory has investigated hepatocyte transplantation using biodegradable
      polymer matrices as an alternative treatment to end-stage liver disease. One of
      the major limitations has been the insufficient survival of an adequate mass of
      transplanted cells. This study investigates a novel method of dynamic seeding and
      culture of hepatocytes in a flow perfusion system. In experiment I, hepatocytes
      were flow-seeded onto PGA scaffolds and cultured in a flow perfusion system for
      24 h. Overall metabolic activity and distribution of cells were assessed by their
      ability to reduce MTT. DNA quantification was used to determine the number of
      cells attached. Culture medium was analyzed for albumin content. In Experiment
      II, hepatocyte/polymer constructs were cultured in a perfusion system for 2 and 7
      days. The constructs were examined by SEM and histology. Culture medium was
      analyzed for albumin. In experiment I, an average of 4.4 X 10(6) cells attached
      to the scaffolds by DNA quantification. Cells maintained a high metabolic
      activity and secreted albumin at a rate of 13 pg/cell/day. In experiment II, SEM
      demonstrated successful attachment of hepatocytes on the scaffolds after 2 and 7
      days. Cells appeared healthy on histology and maintained a high rate of albumin
      secretion through day 7. Hepatocytes can be dynamically seeded onto biodegradable
      polymers and survive with a high rate of albumin synthesis in the flow perfusion
      culture system.

PMID- 10941197
TI  - Evaluation of osteoblast response to porous bioactive glass (45S5) substrates by
      RT-PCR analysis.
AB  - Previous studies have shown that neonatal rat calvaria osteoblasts elaborate
      substantial amounts of extracellular material with bone-like characteristics when
      cultured on porous bioactive glass substrates in vitro. However, the osteoblastic
      response to this material has not been fully characterized. The objective of this
      study was to characterize osteoblast response to porous bioactive glass
      substrates following the expression of the classical markers for osteoblast
      differentiation. In this study we synthesized porous bioactive glass substrates,
      seeded them with osteoblast-like cells (ROS 17/2.8) and followed the temporal
      expression of alkaline phosphatase (AP) activity, as well as the expression of
      mRNA for collagen type I (Coll-1), osteonectin (OSN), osteopontin (OPN),
      osteocalcin (OCN), and bone sialoprotein (BSP). The data confirm that porous
      bioactive glass substrates are capable of supporting the in vitro growth and
      maturation of osteoblast-like cells. At a porosity of 42% and an average pore
      size of 80 microm, the substrates promote the expression and maintenance of the
      osteoblastic phenotype. The results additionally suggest that there is both a
      solution-mediated and a surface-controlled effect on cell activity.

PMID- 10941200
TI  - Enhancing hepatocyte adhesion by pulsed plasma deposition and polyethylene glycol
      coupling.
AB  - Decreased hepatocyte adhesion to polymeric constructs limits the function of
      tissue engineered hepatic assist devices. We grafted adhesion peptides (RGD and
      YIGSR) to polycaprolactone (PCL) and poly-L-lactic acid (PLLA) in order to mimic
      the in vivo extracellular matrix and thus enhance hepatocyte adhesion. Peptide
      grafting was done by a novel technique in which polyethylene glycol (PEG)
      adhesion peptide was linked to allyl-amine coated on the surface of PCL and PLLA
      by pulsed plasma deposition (PPD). Peptide grafting density, quantified by radio
      iodinated tyrosine in YIGSR, was 158 fmol/cm(2) on PLLA and 425 fmol/cm(2) on PCL
      surfaces. The adhesion of hepatocytes was determined by plating 250,000
      hepatocytes/well (test substrates were coated on 12 well plates) and quantifying
      the percentage of adhered cells after 6 h by MTT assay. Adhesion on PCL surfaces
      was significantly enhanced (p < 0.05) by both YIGSR (percentage of adhered cells
      = 53 +/- 7%) and RGD (53 +/- 12%) when compared to control surfaces (31 +/- 8%).
      Hepatocyte adhesion on PLLA was significantly (p < 0.05) enhanced on PLLA-PEG-RGD
      surfaces (76 +/- 14%) compared to control surfaces (42 +/- 19%) and more (68 +/-
      25%) but not statistically significant (p = 0.15) on PLLA-PEG-YIGSR surfaces
      compared to control surfaces. These results indicate that hepatocyte adhesion to
      PCL and PLLA based polymeric surfaces can be enhanced by a novel adhesion peptide
      grafting technique using pulsed plasma deposition and PEG cross-linking.

PMID- 10941201
TI  - Cultured human keratinocytes on type I collagen membranes to reconstitute the
      epidermis.
AB  - The development of new techniques and modifications to overcome some of the
      disadvantages in cultured keratinocyte grafting has been motivated by several
      well-known drawbacks in the use of cultured epithelial autografts such as long
      culture periods, lack of adherence, difficulty in handling, lack of dermal
      substrates, and high costs. Two recent insights have influenced further research.
      On the one hand, it has been shown that the use of undifferentiated proliferative
      cells in fibrin glue suspensions is effective in epithelial reconstitution. On
      the other hand, the enzymatic release of cells from the culture surfaces is a
      critical step leading to at least temporary destruction of anchoring structures
      of the cultured cells. In this study, we tried to combine these two aspects in an
      attempt to modify common modalities of keratinocyte transplantation. To avoid
      dispase dissolving of the cultured cells, keratinocytes were seeded onto bovine
      collagen type I membranes without feeder layers and under serum-free culture
      conditions. Subconfluent monolayers of cultured human keratinocytes were
      transplanted as an upside-down graft on collagen membranes (keratinocyte collagen
      membrane grafts [KCMG], n = 12) after 3 days of culture or as membrane grafts
      alone (n = 12) onto standard nude mice full-thickness wounds. Fully
      differentiated epidermis was found at 21 days after grafting KCMG with
      persistence of human keratinocytes. This study demonstrates that upside-down
      grafts of undifferentiated monolayers of keratinocytes on non-cross-linked bovine
      type I collagen membranes do lead to an early reconstitution of multilayered
      squamous epithelium with enhanced wound healing compared to the control group.
      The upside down KCMG grafting technique is able to transfer actively
      proliferative keratinocytes and simplifies the application compared to
      conventional epithelial sheet grafting.

PMID- 10941202
TI  - Minimally invasive technique of auricular cartilage harvest for tissue
      engineering.
AB  - Tissue engineered human cartilage is presently being utilized in clinical
      research programs in a variety of medical disciplines including otolaryngology,
      urology, and orthopedics. In this study, we present a new methodology for
      auricular cartilage harvest that can be applied to tissue engineering. Eight 16
      week-old pigs were subjected to a traditional open cartilage harvest technique
      involving suture closure, while the other ear was subjected to the closed
      stitchless cartilage harvest, using a 12-gauge core biopsy needle. Surgical time
      was significantly (p < 0.0001) shorter (3.5 +/- 2.8 min for closed vs. 14.4 +/- 5
      min for open), and no sutures where utilized in the closed technique. Sample
      weights were significantly (p < 0.00001) greater (0.115 +/- 0.028 g vs. 0.045 +/-
      0.005 g) for the closed techniques. However, the minimally invasive closed
      technique had fewer incidents of bruising, hematoma, long-term stitch abscess,
      and scarring. Cell culture data shows no disadvantage to either technique with
      regards to cell growth characteristics. Final histological data from donor ears
      indicates favorable results with the minimally invasive technique. This technique
      preserves cell viability and isolation efficiency while decreasing surgical time
      and lessening postoperative complications.

PMID- 10941203
TI  - New pulsatile bioreactor for in vitro formation of tissue engineered heart
      valves.
AB  - Two potential obstacles to the creation of implantable tissue engineered heart
      valves are inadequate mechanical properties (ability to withstand hemodynamic
      stresses) and adverse host-tissue reactions due to the presence of residual
      nondegraded polymer scaffold. In an attempt to address these problems, we
      developed an in vitro cell culture system that provides physiological pressure
      and flow of nutrient medium to the developing valve constructs. It is anticipated
      that in vitro physical stress will stimulate the tissue engineered heart valve
      construct to develop adequate strength prior to a possible implantation. Long
      term in vitro development will be realized by an isolated and thereby
      contamination-resistant system. Longer in vitro development will potentially
      enable more complete biodegradation of the polymeric scaffold during in vitro
      cultivation. This new dynamic bioreactor allows for adjustable pulsatile flow and
      varying levels of pressure. The system is compact and easily fits into a standard
      cell incubator, representing a highly isolated dynamic cell culture setting with
      maximum sterility, optimal gas supply and stable temperature conditions
      especially suited for long-term experiments.

PMID- 10941204
TI  - Patentability of treatment of human beings in Australia.

PMID- 10941205
TI  - Extracellular matrix cell adhesion peptides: functional applications in
      orthopedic materials.
AB  - This review describes research on selected peptide sequences that affect cell
      adhesion as it applies in orthopedic applications. Of particular interest are the
      integrin-binding RGD peptides and heparin-binding peptides. The influence of
      these peptides on cell adhesion is described. Cell adhesion is defined as a
      sequence of four steps: cell attachment, cell spreading, organization of an actin
      cytoskeleton, and formation of focal adhesions. RGD sequences clearly influence
      cell attachment and spreading, whereas heparin-binding sequences appear to be
      less efficient. Collectively, these sequences appear to promote all steps of cell
      adhesion in certain cell types. This review also addresses issues related to
      peptide immobilization, as well as potential complexities that may develop as a
      result of using these versatile cell-binding sequences. Also described are future
      directions in the field concerning use of existing and more sophisticated peptide
      substrata.

PMID- 10941206
TI  - Silicon micromachining to tissue engineer branched vascular channels for liver
      fabrication.
AB  - To date, many approaches to engineering new tissue have emerged and they have all
      relied on vascularization from the host to provide permanent engraftment and mass
      transfer of oxygen and nutrients. Although this approach has been useful in many
      tissues, it has not been as successful in thick, complex tissues, particularly
      those comprising the large vital organs such as the liver, kidney, and heart. In
      this study, we report preliminary results using micromachining technologies on
      silicon and Pyrex surfaces to generate complete vascular systems that may be
      integrated with engineered tissue before implantation. Using standard
      photolithography techniques, trench patterns reminiscent of branched architecture
      of vascular and capillary networks were etched onto silicon and Pyrex surfaces to
      serve as templates. Hepatocytes and endothelial cells were cultured and
      subsequently lifted as single-cell monolayers from these two-dimensional molds.
      Both cell types were viable and proliferative on these surfaces. In addition,
      hepatocytes maintained albumin production. The lifted monolayers were then folded
      into compact three-dimensional tissues. Thus, with the use microfabrication
      technology in tissue engineering, it now seems feasible to consider lifting
      endothelial cells as branched vascular networks from two-dimensional templates
      that may ultimately be combined with layers of parenchymal tissue, such as
      hepatocytes, to form three-dimensional conformations of living vascularized
      tissue for implantation.

PMID- 10941207
TI  - A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve
      regeneration.
AB  - Alternatives to autografts have long been sought for use in bridging neural gaps.
      Many entubulation materials have been studied, although with generally
      disappointing results in comparison with autografts. The purpose of this study
      was to design a more effective neural guidance conduit, to introduce Schwann
      cells into the conduit, and to determine regenerative capability through it in an
      in vivo model. A novel, fully biodegradable polymer conduit was designed and
      fabricated for use in peripheral nerve repair, which approximates the macro- and
      microarchitecture of native peripheral nerves. It comprised a series of
      longitudinally aligned channels, with diameters ranging from 60 to 550 microns.
      The lumenal surfaces promoted the adherence of Schwann cells, whose presence is
      known to play a key role in nerve regeneration. This unique channel architecture
      increased the surface area available for Schwann cell adherence up to five-fold
      over that available through a simple hollow conduit. The conduit was composed of
      a high-molecular-weight copolymer of lactic and glycolic acids (PLGA) (MW
      130,000) in an 85:15 monomer ratio. A novel foam-processing technique, employing
      low-pressure injection molding, was used to create highly porous conduits
      (approximately 90% pore volume) with continuous longitudinal channels. Using this
      technique, conduits were constructed containing 1, 5, 16, 45, or more
      longitudinally aligned channels. Prior to cellular seeding of these conduits, the
      foams were prewet with 50% ethanol, flushed with physiologic saline, and coated
      with laminin solution (10 microg/mL). A Schwann cell suspension was dynamically
      introduced into these processed foams at a concentration of 5 X 10(5) cells/mL,
      using a simple bioreactor flow loop. In vivo regeneration studies were carried
      out in which cell-laden five-channel polymer conduits (individual channel ID 500
      microm, total conduit OD 2.3 mm) were implanted across a 7-mm gap in the rat
      sciatic nerve (n = 4), and midgraft axonal regeneration compared with autografts
      (n = 6). At 6 weeks, axonal regeneration was observed in the midconduit region of
      all five channels in each experimental animal. The cross-sectional area
      comprising axons relative to the open conduit cross sectional area (mean 26.3%,
      SD 10. 1%) compared favorably with autografts (mean 23.8%, SD 3.6%). Our
      methodology can be used to create polymer foam conduits containing longitudinally
      aligned channels, to introduce Schwann cells into them, and to implant them into
      surgically created neural defects. These conduits provide an environment
      permissive to axonal regeneration. Furthermore, this polymer foam-processing
      method and unique channeled architecture allows the introduction of neurotrophic
      factors into the conduit in a controlled fashion. Deposition of different factors
      into distinct regions within the conduit may be possible to promote more
      precisely guided neural regeneration.

PMID- 10941208
TI  - Influence of glial growth factor and Schwann cells in a bioresorbable guidance
      channel on peripheral nerve regeneration.
AB  - Using an established rat peripheral nerve regeneration model, we investigated the
      role of glial growth factor (GGF) in nerve regeneration in combination with a
      novel bioresorbable poly(lactic-co-glycolic) acid (PLGA) guide in vivo. Schwann
      cells, established from a 1-cm segment of excised rat sciatic nerve, were
      isolated and seeded onto nerve guides with or without GGF (n = 24/group). Living
      nerve guides were re-established in these animals, and nerve regeneration was
      assessed over a period of 12 weeks. Histological studies revealed a reduction in
      the total axon count and the number of myelinated axons in the presence of
      exogenously added Schwann cells compared to saline controls. In contrast, the
      addition of GGF alone enhanced the total number of axons and significantly
      increased the number of blood vessels. Although combining GGF with Schwann cells
      negated the enhanced numbers of axons and blood vessels seen with GGF alone, this
      combination resulted in the highest myelination index and the fastest conduction
      velocities recorded. The PLGA guide material did not trigger any histologically
      detectable host response and was permissive for nerve regeneration in this animal
      model. The results from this study demonstrate the potential utility of this
      guide in vivo and establish a promotional role for GGF in nerve regeneration.

PMID- 10941209
TI  - Microencapsulation of normal and transfected L929 fibroblasts in a HEMA-MMA
      copolymer.
AB  - Mouse L929 fibroblasts transfected to express a secreted form of human alkaline
      phosphatase (SEAP) were encapsulated in approximately 400-microm
      poly(hydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA) microcapsules
      as a baseline for the use of genetically engineered cells in encapsulation
      therapy. Although incubation of microcapsules with serum-containing medium
      resulted in maintaining the number of live encapsulated cells with the passage of
      time, incubation in a serum-free medium resulted in a three-fold proliferation of
      the encapsulated cells within a 3-week observation period. Similar to the results
      for incubation with serum-containing medium, co-encapsulation with a bovine
      dermal type I collagen, i.e., the inclusion of a matrix in the core of the
      capsules, resulted in maintenance of the initial number of live cells with the
      passage of time. SEAP measurements indicated that the transfected cells not only
      continued to express the transgene product after encapsulation, but also adapted
      to the capsule microenvironment to secrete SEAP at progressively larger amounts
      with the passage of time. However, SEAP expression only occurred when the
      transfected cells (encapsulated or non-encapsulated) were cultivated in serum
      containing medium.

PMID- 10941210
TI  - Encapsulation matrices for neurotrophic factor-secreting myoblast cells.
AB  - Encapsulated-cell therapy is an emerging technology that entails implantation of
      cell-containing devices that secrete therapeutic factors. One potential
      application of this technology is the delivery of neurotrophic factors to treat
      neurodegenerative disease. These devices typically use an internal matrix to
      serve as a cell scaffold. This study compares collagen-coated polyethylene
      terephthalate (PET) yarn scaffold versus collagen as a matrix for engineered
      C2C12 myoblasts. C2C12 cells transfected to secrete ciliary neurotrophic factor
      (CNTF) were immobilized in matrices and encapsulated into hollow fiber membrane
      devices. Encapsulated cells were monitored in vitro for viability, morphology,
      and factor secretion. Two independent methods (histology assessment and metabolic
      assay) were used to estimate viable cell density; a high correlation between the
      methods was found. After 4 weeks, encapsulated devices with PET scaffold had an
      almost nine-fold greater number of viable cells compared to collagen. PET matrix
      devices contained a thick annulus of compact, highly oriented cells. Collagen
      matrix devices contained sparse viable cells in a thin rim. Secretion assays
      showed cells in PET matrix released approximately four-fold the amount of CNTF
      versus cells in collagen (averaging 542 and 129 ng/day per device for PET and
      collagen matrix, respectively). The choice of encapsulation matrix was found to
      have a profound effect on cell morphology, level of secreted factor, and
      viability of encapsulated C2C12 cells.

PMID- 10941211
TI  - Viability of HEMA-MMA microencapsulated model hepatoma cells in rats and the host
      response.
AB  - Small diameter hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA; 75% HEMA)
      microcapsules containing an aggregate of viable rat hepatoma H4IIEC3 cells, after
      implantation into an omental pouch in Wistar rats, contained viable cells at 7
      days but not 14 days. A similar transplantation of microencapsulated aggregates
      of human hepatoma HepG2 cells did not result in viable cells even at 7 days. The
      loss of viability was attributed to the tissue reaction, because both
      encapsulated cell types remained viable in vitro. However, it is not clear if the
      cells lost their viability in vivo, leading to the aggressive tissue reaction or
      if the latter caused the cells to starve or otherwise die. The tissue reactions
      to microcapsules containing rat or human hepatoma cells at day 1 was one cell
      layer thick and avascular. At later times, tissue reactions were comprised of
      three regions: macrophages, fibroblasts, and some foreign body giant cells
      apposed to the polymer membrane, a dense region of fibroblasts and collagen, and
      a region of vascularized granulation tissue. Prompt vascularization of the tissue
      reactions occurred after 4 days and was maintained for up to 14 days. Even at 14
      days, immune cells were observed, suggesting a continued immune response toward
      antigens shed from the encapsulated cells.

PMID- 10941212
TI  - Fabrication of a trileaflet heart valve scaffold from a polyhydroxyalkanoate
      biopolyester for use in tissue engineering.
AB  - Previously, we reported the implantation of a single tissue engineered leaflet in
      the posterior position of the pulmonary valve in a lamb model. The major problems
      with this leaflet replacement were the scaffold's inherent stiffness, thickness,
      and nonpliability. We have now created a scaffold for a trileaflet heart valve
      using a thermoplastic polyester. In this experiment, we show the suitability of
      this material in the production of a biodegradable, biocompatible scaffold for
      tissue engineered heart valves. A heart valve scaffold was constructed from a
      thermoplastic elastomer. The elastomer belongs to a class of biodegradable,
      biocompatible polyesters known as polyhydroxyalkanoates (PHAs) and is produced by
      fermentation (Metabolix Inc., Cambridge, MA). It was modified by a salt leaching
      technique to create a porous, three-dimensional structure, suitable for tissue
      engineering. The trileaflet heart valve scaffold consisted of a cylindrical stent
      (1 mm X 15 mm X 20 mm I.D.) containing three valve leaflets. The leaflets were
      formed from a single piece of PHA (0.3 mm thick), and were attached to the
      outside of the stent by thermal processing techniques, which required no
      suturing. After fabrication, the heart valve construct was allowed to crystallize
      (4 degrees C for 24 h), and salt particles were leached into doubly distilled
      water over a period of 5 days to yield pore sizes ranging from 80 to 200 microns.
      Ten heart valve scaffolds were fabricated and seeded with vascular cells from an
      ovine carotid artery. After 4 days of incubation, the constructs were examined by
      scanning electron microscopy. The heart valve scaffold was tested in a pulsatile
      flow bioreactor and it was noted that the leaflets opened and closed. Cells
      attached to the polymer and formed a confluent layer after incubation. One
      advantage of this material is the ability to mold a complete trileaflet heart
      valve scaffold without the need for suturing leaflets to the conduit. Second
      advantage is the use of only one polymer material (PHA) as opposed to hybridized
      polymer scaffolds. Furthermore, the mechanical properties of PHA, such as
      elasticity and mechanical strength, exceed those of the previously utilized
      material. This experiment shows that PHAs can be used to fabricate a three
      dimensional, biodegradable heart valve scaffold.

PMID- 10941213
TI  - Patent issue: supplier liability in medical implants and devices: the
      "Biomaterials Access Assurance Act".

PMID- 10941214
TI  - Abstracts of "The 2nd annual meeting of the japanese society for tissue
      engineering"

PMID- 10941215
TI  - The growth and morphological behavior of salivary epithelial cells on matrix
      protein-coated biodegradable substrata.
AB  - The purpose of this study was to examine the growth and morphology of a salivary
      epithelial cell line (HSG) in vitro on several biodegradable substrata as an
      important step toward developing an artificial salivary gland. The substrates
      examined were poly-L-lactic acid (PLLA), polyglycolic acid (PGA), and two co
      polymers, 85% and 50% PLGA, respectively. The substrates were formed into 20- to
      25-mm disks, and the cells were seeded directly onto the polymers or onto
      polymers coated with specific extracellular matrix proteins. The two copolymer
      substrates became friable over time in aqueous media and proved not useful for
      these experiments. The purified matrix proteins examined included fibronectin
      (FN), laminin (LN), collagen I, collagen IV, and gelatin. In the absence of
      preadsorbed proteins, HSG cells did not attach to the polymer disks. The cells,
      in general, behaved similarly on both PLLA and PGA, although optimal results were
      obtained consistently in PLLA. On FN-coated PLLA disks, HSG cells were able to
      form a uniform monolayer, which was dependent on time and FN concentration.
      Coating of disks with LN, collagen I, and gelatin also promoted monolayer growth.
      This study defines the conditions necessary for establishing a monolayer
      organization of salivary epithelial cells with rapid proliferation on a
      biodegradable substrate useful for tissue engineering.

PMID- 10941216
TI  - Biodegradable foam coating of cortical allografts.
AB  - Clinical outcomes of bone allograft procedures may be improved by modifying the
      surface of the graft with an osteoconductive biopolymeric coating. In this
      comparative in vitro study, we evaluated the dimensional stability, mechanical
      strength, hydrophilicity, and water uptake of biodegradable foams of
      poly(propylene fumarate) (PPF) and poly(d,l-lactic-co glycolic acid) (PLGA) when
      applied as surface coatings to cortical bone. Cortical bone samples were divided
      into four groups: Type I, untreated bone; Type II, laser-perforated bone; Type
      III, partially demineralized bone; and Type IV, laser-perforated and partially
      demineralized bone. Results show that PPF wets easily, achieving 12.5% wt/wt in
      30 min. Compressive tests on the PPF foam material showed that the compressive
      strength was 6.8 MPa prior to in vitro incubation but then gradually reduced to
      1.9 MPa at 8 weeks. Push-out and pulloff strength tests showed that initially
      both PPF and PLGA foam coatings had comparable adherence strengths to the
      cortical bone samples (100-150 N). When additional geometrical surface alteration
      by perforation and demineralization of the bony substrate was employed, in vitro
      adherence of the PPF foam coating was further increased to 120 N, demonstrating a
      statistically significant improvement of push-out strength throughout the entire
      8-week observation period (p<0.0002 for all four data points). The pore geometry
      of PPF-foam coatings changed little over the 2-month evaluation period. In
      comparison, PLGA foam coating around the cortical bone samples rapidly lost
      structure with a decrease of 67% in strength seen after 1-week in vitro
      incubation. These new types of bone allografts may be particularly useful where
      the use of other replacement materials is not feasible or practical.

PMID- 10941217
TI  - Identifying a site for maximum delivery of oxygen to transplanted cells.
AB  - For in vivo cell implantation techniques to be successful, the energy and
      metabolic substrate requirement of the cells being grown must be met. Certain
      cells with high-energy requirements (e.g., hepatocytes, pancreatic island cells)
      experience a high degree of cell death after implantation due to a limited supply
      of oxygen. We proposed that the pleural cavity might be an oxygen-rich
      environment and hence an excellent site for cell implantation. To test the
      hypothesis that the delivery of oxygen to the pleural cavity is directly
      proportional to the inspired oxygen concentration we measured the pO(2) of saline
      instilled in the pleural cavity as compared to that of the peritoneal cavity. We
      postulated that the physiologic basis for any difference was the result of direct
      diffusion of oxygen into the pleural space across the alveoli. The study was
      conducted on sheep (n = 6), after induction of general anesthesia, in two phases,
      control and experimental. Saline was instilled into the peritoneal and pleural
      cavities via catheters, after equilibration at given FiO(2), the pO(2) of the
      paline aspirated from the two cavities was compared. In the experimental group,
      animals were sacrificed (no circulation) and ventilated. The same sequence of
      steps as in the control phase were repeated. In the control group, the pO(2) of
      saline aspirated from the pleural cavity approached the arterial pO(2) at all
      FiO(2) levels. The pO(2) of the peritoneal saline aspirate fell over time. In the
      experimental phase (no circulation), the pO(2) of the pleural cavity saline rose
      to >400 mm Hg. We conclude that this is a result of direct diffusion and is a
      potential source of unlimited oxygen supply not dependent on vascular supply.

PMID- 10941218
TI  - Galalpha(1,3)Gal epitope in porcine small intestinal submucosa.
AB  - Small intestinal submucosa (SIS) is a naturally occurring, acellular biomaterial
      derived from porcine jejunum, which promotes constructive tissue remodeling when
      applied as a xenogeneic graft material. Galactosyl-alpha(1,3)galactose (Gal) is a
      cell-associated epitope responsible for hyperacute rejection of porcine whole
      organ xenografts in primates. Because SIS is harvested from porcine tissue, it
      may contain the Gal epitope. The goals of this study were to determine if Gal is
      present in SIS and, if it is present, to determine if human serum complement can
      be activated in vitro following exposure to porcine-derived SIS. SIS was probed
      for Gal by immunohistochemical methods and by lectin-peroxidase staining. SIS
      stained strongly positive with human serum, which contains naturally occurring
      antibodies to Gal, followed by anti-immunoglobulin G (IgG) or anti-IgM peroxidase
      conjugate. Blocking with the lectin I-B(4), which is specific for the Gal
      epitope, decreased the intensity of staining. Exposure of SIS to alpha
      galactosidase reduced staining to negligible amounts. The Gal epitope is
      distributed transmurally throughout the SIS material. Subtyping of the
      immunoglobulins that bind to SIS showed that IgG(2) is the major immunoglobulin
      of human plasma that binds to SIS. SIS did not activate complement in vitro as
      measured by radioimmunoassay for C3a.

PMID- 10941219
TI  - eNOS-overexpressing endothelial cells inhibit platelet aggregation and smooth
      muscle cell proliferation in vitro.
AB  - Endothelial cell seeding of synthetic small diameter vascular grafts (SSDVG) has
      been shown to diminish thrombosis and intimal hyperplasia, resulting in improved
      graft patency. However, endothelial cell retention on seeded grafts when exposed
      to physiological shearing conditions remains poor. We report that the genetic
      engineering of endothelial cells to overexpress endothelial nitric oxide synthase
      (eNOS), may create improved anti-thrombotic and anti-hyperplastic endothelial
      cell phenotypes for SSDVG seeding. eNOS-overexpressing endothelial cells may
      potentially overcome the biochemical loss due to shear induced reduction in
      endothelial cell coverage on SSDVG. Bovine aortic endothelial cells (BAEC) were
      transfected with the human eNOS gene, and co-incubated with either human whole
      blood or bovine aortic smooth muscle cells (BASMC) in vitro. eNOS-transfected
      BAEC significantly overexpressed eNOS compared to control beta-Gal-transfected
      and untransfected BAEC up to 120 h post transfection. In co-incubation and co
      culture assays, human platelet aggregation decreased by 46% and BASMC
      proliferation decreased by 67.2% when compared to incubation with untransfected
      BAEC.

PMID- 10941220
TI  - Comparison of analytical methods for quantitation of isolated porcine hepatocyte
      yields.
AB  - As cell-based therapies receive approval for clinical evaluation and use, the
      development of reliable methods to quantify cell number and control the dose of
      therapy delivered is becoming increasingly important. An example is the
      determination of the number and volume of primary porcine hepatocytes used in an
      extracorporeal treatment for patients with liver disease. Conventional cell
      counting using optical microscopy was compared against two alternate methods to
      quantify isolated porcine hepatocytes: (1) automated cell counting using a
      commercially available particle characterization instrument, and (2) quantitation
      by cell mass. Methods were compared based on accuracy, precision, specificity,
      linear range, and ruggedness. The automated method delivered substantially
      improved accuracy, precision, and ruggedness when compared to the conventional
      optical method. It also provided valuable information about the size distribution
      of cell preparations, which often contained clumps of cells, and showed that
      processing steps such as cryopreservation can alter the size characteristics of a
      cell population. The automated method was also faster, and was well suited to use
      in a commercial manufacturing process. The mass-based method was simple and
      inexpensive, but suffered from nonlinearity at low cell concentrations. Automated
      cell quantitation using a commercially available particle characterization
      instrument proved to be the preferred method for obtaining accurate and
      consistent porcine hepatocyte counts in a timely manner.

PMID- 10941221
TI  - In vivo magnetic resonance imaging and relaxometry study of a porous hydrogel
      implanted in the trapezius muscle of rabbits.
AB  - In vivo magnetic resonance imaging (MRI) and relaxometry were performed to assess
      noninvasively the tissue reaction and the biological integration of hydrogels
      made of poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) after implantation in
      the trapezius muscle of rabbits. The benefits of incorporating RGD peptide
      sequences in the polymer backbone were also investigated. The histological status
      of each implant was probed by the trend of their transversal relaxation times,
      T(2), while their biocompatibility was evaluated by analyzing the host tissue
      response through the evolution of the relaxation times of the adjacent muscle
      tissue. MR results showed the good acceptability of both hydrogels by the host
      tissue. The transversal relaxation curves of each implant exhibited two distinct
      phases as a function of implantation time: (1) a monoexponential phase, dominated
      by the influx of fluids inside the implants; and (2) a biexponential phase
      related to the infiltration of cells and the granulation tissue formation within
      the porous structure of each polymer. These MR findings were correlated with the
      results of conventional histological analyses. The present study demonstrates the
      effectiveness of MR methods in noninvasively monitoring the biocompatibility and
      histological status of implanted porous biomaterials.

PMID- 10941222
TI  - De novo formation of adipose tissue by controlled release of basic fibroblast
      growth factor.
AB  - De novo adipogenesis at the implanted site of a basement membrane extract
      (Matrigel) was induced through controlled release of basic fibroblast growth
      factor (bFGF). bFGF was incorporated into biodegradable gelatin microspheres for
      its controlled release. When the mixture of Matrigel and bFGF-incorporated
      gelatin microspheres was implanted subcutaneously into the back of mice, a
      clearly visible fat pad was formed at the implanted site 6 weeks later.
      Histologic examination revealed that the de novo formation of adipose tissue
      accompanied with angiogenesis was observed in the implanted Matrigel at bFGF
      doses of 0.01, 0.1, and 1 microg/site, the lower and higher doses being less
      effective. The de novo formation induced by the bFGF-incorporated microspheres
      was significantly higher than that induced by free bFGF of the same dose. The
      mRNA of a lipogenesis marker protein, glycerophosphate dehydrogenase, was
      detected in the formed adipose tissues, biochemically indicating de novo
      adipogenesis. Free bFGF, the bFGF-incorporated gelatin microspheres, or Marigel
      alone and bFGF-free gelatin microspheres with or without Matrigel did not induce
      formation of adipose tissue. This de novo adipogenesis by mixture of Matrigel and
      the bFGF-incorporated gelatin microspheres will provide a new idea for tissue
      engineering of adipose tissue.

PMID- 10941223
TI  - The American Inventors Protection Act of 1999.

PMID- 10941224
TI  - Ethics Summit. II: Creating a sustaining structure for an ethics alliance of oral
      health organizations.

PMID- 10941225
TI  - Sustaining alliances for integrity.
AB  - Research in business ethics has shown that value-grounded organizations
      outperform their counterparts in business terms and that industries can
      successfully regulate themselves. The market in health care, systems theory, and
      stakeholder analysis are used to generate a set of five potential core values to
      sustain an Ethics Alliance of Oral Health Organizations.

PMID- 10941226
TI  - Discursive ethics, conflicts of interest, and the elephant in the reception area.

PMID- 10941227
TI  - There are no spectators in ethics.

PMID- 10941228
TI  - The search for a common ethic: the Ethics Alliance of Oral Health Organizations.

PMID- 10941229
TI  - The infinity of opportunity: breaking barriers to technological change in
      dentistry.
AB  - This essay characterizes the nature of the technologically current dental office
      and identifies challenges to be overcome in accelerating the introduction of
      technology. These challenges include dentists' preference for serial introduction
      of incremental change, lack of a network for communicating information on
      technology, the dental market of small and independent offices that make it
      difficult for manufacturers to finance innovative products, and the need to
      integrate technological change in dental education.

PMID- 10941230
TI  - Technology meets ergonomics in the dental clinic: new toys for old games?
AB  - Although there have been considerable advances in dental equipment, the
      introduction of such technology has often been piecemeal and "rushed to market."
      As a result there has been insufficient attention paid to ergonomic
      considerations and a systematic approach to, and theory of, dental ergonomics
      have not yet emerged.

PMID- 10941231
TI  - Translating clinical practice into evidence-based research through the use of
      technology.
AB  - Gaps exist in the extent to which technology has been fully integrated into
      dental practices. This is partially the result of continuously emerging
      technologies and partially attributable to different attitudes among dentists
      toward innovation. Further development of Evidence-Based Dentistry is needed
      before it becomes a productive and widely used part of practice.

PMID- 10941232
TI  - The future is coming and it will be amazing: computers in dentistry.
AB  - The computer in the dental office, especially at chairside, provides both "high
      tech" and "high touch" benefits. Single entry of data has the benefit of accuracy
      and time savings. It also makes data available regarding the practice in an easy
      to-use fashion. Some suggestions are offered to those contemplating the addition
      of a computer system to their offices.

PMID- 10941233
TI  - ADA Department on Dental Informatics.

PMID- 10941234
TI  - The ethical complexities of dual relationships in dentistry.
AB  - Dual relationships hold the potential for conflict because each relationship
      involves expectations for behavior and these expectations may be inconsistent.
      Examples are provided in the dental situation involving romantic, social,
      financial, and familial second relationships. Care must be exercised by dentists
      not to abuse the power of their position.

PMID- 10941235
TI  - A new look at dentistry's first ethical question.

PMID- 10941236
TI  - Identity.

PMID- 10941237
TI  - Error in medicine. A grim fairy tale.

PMID- 10941238
TI  - Snake oil and empty promises.

PMID- 10941239
TI  - JCAHO provides a good start.

PMID- 10941240
TI  - JCAHO: is that your final answer?

PMID- 10941241
TI  - Indicators of performance: are errors the initial driving force?

PMID- 10941242
TI  - Utilization review in Maryland hospitals. A synopsis of the Maryland Insurance
      Administration's study.

PMID- 10941243
TI  - Medical office survival. Activity based costing for physicians.

PMID- 10941244
TI  - Independence for people with disabilities. A physician's primer on assistive
      technology.

PMID- 10941245
TI  - [Oncology caught between economics and efficiency].

PMID- 10941246
TI  - [Infusiontherapy with 5-fluorouracil ("infusional" 5-FU) in solid tumors].
AB  - BACKGROUND: 5-FU is an important anticancer agent for many tumor entities.
      Because of the historical development of this compound it was predominantly
      administered as a bolus application, although it was well known that the
      antineoplastic activity of this antimetabolite is improved by prolonged
      administration schedules (protracted infusion ["infusional"] of 5-FU). Since port
      a-cath systems and portable pumps became available, "infusional" 5-FU containing
      chemotherapies were intensively investigated in various tumors known to be
      susceptible to 5-FU. INDICATIONS: The largest experience with "infusional" 5-FU
      +/- folinic acid +/- other cytostatic drugs exists in gastrointestinal tumors.
      Meanwhile this way of 5-FU application is well established in the first- and
      second-line chemotherapy of metastatic colorectal and gastric cancer where it
      contributes to a clinically relevant improvement of the prognosis of these
      tumors. Other tumor entities where "infusional" 5-FU-based chemotherapies showed
      first positive results are i.e. breast cancer and esophageal cancers.

PMID- 10941248
TI  - [Economic evaluation in oncology].
AB  - With the growing financial restrictions, economic evaluations in public health
      are becoming increasingly relevant. The pressure on justifying increasing costs
      is considerable, particularly in the field of oncology, where highly acclaimed
      treatment methods exist and are newly developed. In order to determine the
      efficiency of a medical measure, different study types of varying complexity were
      designed and employed according to the conditions of the structure. The
      advantages and disadvantages of the different study forms are discussed on the
      basis of the folinic acid example.

PMID- 10941247
TI  - [Nonhormonal prevention of breast cancer].
AB  - BACKGROUND: Despite the use of currently available drug therapies, the life
      expectancy of patients with metastasized breast cancer can still only be extended
      by about 14 to 16 months in comparison to a completely untreated patient
      population. In light of these figures, and the associated economic costs, all
      possible means to reduce the incidence of the disease are of great potential
      importance and must be examined seriously. PREVENTION: Increased consumption of
      alcohol is a risk factor for breast cancer. Increased intake of phytoestrogens,
      dietary fiber, and beta-carotene as well as regular physical activity and normal
      body weight lower the risk of breast cancer. The increased risk of breast cancer
      associated with alcohol consumption can be reduced by adequate intake of folate.
      The significance of retinoids is at present ambiguous. CONCLUSION: Effective
      preventive measures, along with adequate early detection schemes, are the best
      means of reducing mortality due to breast cancer. Both folate and retinoids
      deserve to be subjected to further studies. It would also be desirable to
      supplement currently ongoing adjuvant therapy trials with studies examining the
      use of folate versus placebo.

PMID- 10941249
TI  - [Economic criteria for covering medical interventions by the German Public Health
      Insurance].
AB  - Decisions about covering a medical intervention by German public health
      insurances are made by the "Bundesausschuss". Such decisions are subject to
      medical and economic considerations. The methods of these evaluations are
      internationally accepted. Any new intervention has to show effectiveness,
      efficacy, and consider cost-effectiveness.

PMID- 10941251
TI  - [Thiazolidinediones in type 2 diabetes].

PMID- 10941250
TI  - [The transplant pharmacy].

PMID- 10941252
TI  - [Salmonella enterica infections].

PMID- 10941253
TI  - [Creatine--placebo or useful supplement?].

PMID- 10941254
TI  - [New reference values for nutritional requirements].

PMID- 10941255
TI  - Homocysteine: a history in progress.
AB  - This paper shows that the linkage between basic science and clinical research has
      characterized the field of sulfur amino acid metabolism since 1810, when
      Wollaston isolated cystine from a human bladder stone. The nature and
      consequences of this relationship are discussed.

PMID- 10941256
TI  - Methylenetetrahydrofolate reductase polymorphisms, folate, and cancer risk: a
      paradigm of gene-nutrient interactions in carcinogenesis.
AB  - Recent epidemiologic studies suggest that common polymorphisms of
      methylenetetrahydrofolate reductase (MTHFR) with allele frequencies up to 35% in
      the general North American population may modulate cancer risk. In some cancers,
      folate and other nutrients involved in the MTHFR metabolic pathway appear to
      interact with MTHFR polymorphisms to further modify cancer risk. In
      carcinogenesis, MTHFR polymorphisms thus provide a paradigm of gene-nutrient
      interactions, an emerging and important topic in the field of nutrition and
      cancer. Furthermore, MTHFR polymorphisms and MTHFR-nutrient interactions provide
      an opportunity to identify an ideal target group of individuals, at high risk of
      developing cancer, for rational, effective, and safe chemoprevention using these
      nutrients.

PMID- 10941257
TI  - Leptin and bone: does the brain control bone biology?
AB  - The means by which obesity leads to high bone density and protects individuals
      from osteoporosis is not known. The study of bone biology in two mouse models of
      obesity, leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice,
      points to a role for leptin in the control of bone density. When leptin action is
      missing in these mice, bone density is high. This is true despite concurrent
      hypogonadism and hypercortisolism, two strong proresorptive signals that would
      normally lead to low bone density. Curiously, leptin does not have a direct
      effect on osteoblasts, which suggests the existence of a central, neuroendocrine
      pathway that controls bone mass.

PMID- 10941258
TI  - Retinoic acid induces the degradation of the leukemogenic protein encoded by the
      promyelocytic leukemia gene fused to the retinoic acid receptor alpha gene.
AB  - Acute promyelocytic leukemia (APL) cells carry a mutated gene that is the result
      of a translocation in which the retinoic acid receptor alpha (RAR alpha) gene is
      fused to the promyelocytic leukemia (PML) gene, coding for a fusion protein,
      PML/RAR alpha. Its presence is the single event that causes APL in transgenic
      mice. All-trans-retinoic acid (atRA) induces the proteolytic degradation of
      PML/RAR alpha by ubiquitination and proteolysis. RAR alpha itself is also
      degraded by atRA treatment, a process representing a possible feedback mechanism
      to turn off RAR alpha's stimulation of transcription.

PMID- 10941259
TI  - Low nutrient intake contributes to adverse clinical outcomes in hospitalized
      elderly patients.
AB  - A prospective cohort study on hospitalized elderly patients revealed that
      inadequate nutrient intake during hospitalization was associated with adverse
      clinical outcomes and increased morbidity. Because this occurred in patients who
      were initially assessed as being in good health, it emphasizes the need for
      continuous nutritional surveillance of hospitalized elderly patients.

PMID- 10941260
TI  - Vitamin D-deficient rickets: a multifactorial disease.
AB  - We present a case of an African-American child with vitamin D-deficient rickets.
      In addition to being solely breast-fed for the period of 1 year, he resided in
      New England, where exposure to ultraviolet light is limited owing to its northern
      latitude and long cold winters. He presented with classical signs of nutritional
      rickets and was immediately responsive to treatment with vitamin D
      supplementation.

PMID- 10941261
TI  - [Basic micro-electrophysiologic techniques used in neurobiology].
AB  - Problems of application of microelectrophysiological techniques in neurobiology
      are addressed. Authors focused on five basic recording techniques: micro-EEG,
      multi unit activity, single unit activity, intracellular recording and patch
      clamp techniques.

PMID- 10941262
TI  - [Use of trans-slice technique for microencephalographic examinations in vitro].
AB  - The present paper reviews the experimental data concerning the use of trans-slice
      preparation technique in investigation of theta-like activity generation in the
      limbic cortex. Specific aspects of the technical arrangement of the hippocampal
      formation and entorhinal cortex microelectroencephalographic registration were
      emphasized.

PMID- 10941263
TI  - [Microelectrode methods applied to investigate plant responses].
AB  - Electrophysiological methods, such as intracellular potential recording, ion
      activity measurements, patch-clamp were described. Special attention was paid to
      their modifications allowing application to plant cells.

PMID- 10941264
TI  - [Field potential recording for investigation of synaptic plasticity in vitro].
AB  - The in vitro brain slice preparations have been widely employed for investigation
      of the cellular mechanisms underlying long-term potentiation and long-term
      depression of synaptic transmission in the rodent hippocampus. The determination
      of spatiotemporal patterns of activation by means of current source-density
      analysis of evoked field potentials allows for the use of field potential
      recording in the research on neocortical synaptic plasticity, in particular in
      horizontal connections of the motor cortex.

PMID- 10941265
TI  - [Intracellular ion channels: properties, function and experimental methodology].
AB  - Ion channels selective for potassium or chloride ions are present in membranes of
      intracellular organelles such as mitochondria, sarcoplasmic (endoplasmic)
      reticulum, nucleus, synaptic vesicles, and chromaffin, and zymogen granules. They
      are probably important in cellular events such as compensation of electrical
      charges during intracellular transport of Ca2+ and H+ and regulation of organelle
      volume changes. This review describes the basic properties, and current
      hypotheses concerning the functional role, and some aspects of experimental
      methodology of intracellular ion channels studies.

PMID- 10941266
TI  - [Bacterial ion canals].
AB  - After an overview of potassium and chloride ion channels found in bacterial inner
      membrane this review focuses on mechanosensitive ion channels from the inner
      membrane of Escherichia coli. Mechanosensitive channels, MscL and MscS, have
      major roles in managing the transition from high to low environments. Biochemical
      and genetic studies of MscL, combined with structural information derived from X
      ray crystalography, have brought the knowledge of how a mechanosensitive channel
      senses membrane tension. Physiological studies on MscL and on MscS have
      demonstrated how the mechanosensitive channels contribute to the bacterial
      membrane response upon hypo-osmotic stress.

PMID- 10941267
TI  - [Photophobic response in Stentor coeruleus--electrophysiologic investigations].
AB  - It is widely known that the phototransduction process in vertebrate photoreceptor
      cells are mediated by cGMP-gated ionic channels. The recent electrophysiological
      study showed that the cGMP-gated channels are also present in light sensitive
      protozoan ciliate Stentor coeruleus. These channels might play a key role in
      phototransduction process which leads to the photophobic behavior in the ciliate.
      The basic biophysical and pharmaceutical properties of cGMP-gated channels in
      Stentor indicate high similarity to those in vertebrate photoreceptor cells.

PMID- 10941268
TI  - [Application of electrophysiological methods in vivo to study circadian clock
      mechanisms in mammals].
AB  - The suprachiasmatic nuclei (SCN) of the hypothalamus and the intergeniculate
      leaflet (IGL) of the thalamic lateral geniculate complex are two main oscillators
      for circadian timing system. A lot of anatomical evidences indicated a strong
      neuronal connections between SCN and IGL. Relatively less, however, is know about
      the electrophysiology and functional interactions between SCN and IGL. The
      spontaneous firing rate of SCN neurons exhibits a remarkable circadian rhythm
      with a higher activity in the day and a lower at the night both in vivo and in
      vitro preparations. However, these rhythms my represent only clock output rather
      then the intrinsic clock mechanism. Last data described for the first time
      ultradian rhythmic neuronal oscillation recorded in vivo in the rat SCN and IGL.
      These isoperiodic phasic discharge probably constitute a basis necessary to
      generate circadian rhythms in mammals.

PMID- 10941269
TI  - [Anatomic and functional identification of sensory neurons in neurophysiologic
      studies].
AB  - The electrophysiological studies indicate that peripheral autonomic and primary
      sensory neurones display a wide variety of ionic currents. The experiments aimed
      at biophysical and pharmacological analysis of ionic currents are frequently
      performed on isolated neurones devoid of axones and dendrites. Consequently the
      ionic currents recordings are limited to the cell soma. The function of somatic
      ionic channels is largely unknown. We suggest that the functional meaning of the
      somatic ionic currents can be facilitated by analysis currents properties in
      functionally identified neurones. Examples are given of different biophysical and
      pharmacological currents properties in cardiac, glandular, cutaneous and muscular
      sympathetic neurones. It is concluded that the resting and reflex activity in
      different categories of sympathetic neurones may be profoundly affected by the
      biophysical properties of ionic channels expressed in their soma.

PMID- 10941270
TI  - [Effects of steroid hormones on nicotinic acetylcholine receptor channel
      kinetics].
AB  - Classically steroid hormones acts through genomic mechanism. In the last period
      there is more evidence that some steroid hormones exert fast (in order of
      seconds) effects on membrane receptors. In the presented work we analysed the
      effects of some steroid hormones on muscle acetylcholine receptor (AChR) channel
      kinetics. We divided steroid hormone on two groups which exert different effects.
      The first group including hydrocortisone (HC), corticosterone (COR),
      dexamethasone decrease the mean open time increasing the number of openings in
      bursts. The effects do not depend on agonist concentration. Some effects of HC
      and COR are voltage-dependent. The mechanism of such voltage dependent action
      caused by steroids hormones that are uncharged molecules, is unknown. Some
      experiments suggest however that an agonist molecule is involved in the mechanism
      of steroid action. The second group consists of progesterone, some of its
      derivatives and deoxycorticosterone. For this group the most evident effect was
      decrease in the probability of openings without a decrease in the mean open time.
      The effect depends on agonist concentration, suggesting an involvement of an
      agonist molecule in the mechanism. For this hormones an involvement of an charged
      agonist molecule does not however induce a voltage dependency. Most probably two
      groups of steroids acts on different part of the AChR. The localization of a
      steroid action site can be crucial for inducing voltage dependency.

PMID- 10941271
TI  - [Modification of bioelectric functions in the nervous system as a result of
      neurotoxin action].
AB  - Natural neurotoxins are promising molecules in the actual search for the
      development of alternative pest management since chemical insecticides pose
      unacceptable risks to the environment and to health. The aim of the article is to
      describe the application of two electrophysiological methods (double-oil-gap
      technique used on cockroach isolated giant axon and microelectrode technique used
      on cockroach neurosecretory DUM cells in situ) to study neurotoxin effects on
      insect nervous system function.

PMID- 10941272
TI  - [Regulation of potassium channel function in T lymphocytes by intracellular
      second messengers for calcium, cyclic AMP and membrane lipid metabolites].
AB  - This review focuses on the influence of well-known intracellular second
      messengers on the activity of potassium channels expressed in human T
      lymphocytes. Basic biophysical properties of the channels are briefly presented.
      Available data on the regulatory role of intracellular calcium and cyclic AMP is
      reviewed. Finally, a possible influence of lipid compounds, especially high
      density lipoproteins, lysophospholipids and sphingolipids, on the expression and
      activity of potassium channels in human T lymphocytes is discussed.

PMID- 10941273
TI  - [Electrophysiologic tests for testing the effects of antidepressant drugs and
      corticosterone on reactivity of serotonin receptors in the hippocampus].
AB  - Disturbances in the serotonin (5-HT) system and the limbic-hypothalamo-pituitary
      adrenal axis (LHPA) have been implicated in the pathophysiology of depression. It
      is well established that hippocampus is a central component of limbic circuitry
      that participates in the modulation of cognition, mood and behavior, and is
      involved in the control of the LHPA axis. Therefore, the hippocampus provides a
      unique environment to study the interplay between serotonergic system,
      antidepressants and corticosteroids. Activity of hippocampal cells can be
      modulated by 5-HT via inhibitory 5-HT1A and excitatory 5-HT4 receptors. Repeated
      treatment with antidepressants increases the responsiveness of hippocampal
      pyramidal neurons to the 5-HT1A and attenuates the responsiveness to the 5-HT4
      receptor agonists, with a time course which correlates with the delayed onset of
      the therapeutic effect of antidepressants in humans. Moreover, repeated
      corticosterone, which may constitute a model of a prolonged nonadaptable stress,
      has opposite effect on hippocampal responsiveness to the 5-HT1A and 5-HT4
      receptor activation. Such an action results in an enhancement of the 5-HT
      mediated inhibition by antidepressants and a reduction in the inhibitory effect
      of 5-HT by corticosterone which may be relevant to antidepressant/antiaxiety and
      proaxiety effects, respectively, of both treatments.

PMID- 10941274
TI  - [Electrophysiological description of synaptic transmission and its modulation by
      pharmacologic factors].
AB  - Synaptic transmission between neurons plays a key role in signal transduction in
      the central nervous system (CNS). Postsynaptic currents can be routinely recorded
      using the patch-clamp technique but mechanisms underlying their kinetics are not
      entirely clear. Model simulations and experimental evidence indicate that the
      time course of synaptic agonist is extremely fast and short lasting implying that
      activation of postsynaptic receptors takes place in conditions of extreme non
      equilibrium. For this reason, studies of postsynaptic receptors' kinetics
      requires ultrafast agonist application techniques able to mimic synaptic
      conditions, the goal that only recently has been technically achieved. In the
      present paper, examples of kinetic studies of synaptic currents and current
      responses to ultrafast agonist applications are presented. Examples are given
      that pharmacological modulation of synaptic receptors strongly depends on the non
      equilibrium conditions of receptors' activation. Application of kinetic studies
      to determine subtypes of synaptic receptors are also presented and discussed.

PMID- 10941275
TI  - Biobehavioral responses to stress in females: tend-and-befriend, not fight-or
      flight.
AB  - The human stress response has been characterized, both physiologically and
      behaviorally, as "fight-or-flight." Although fight-or-flight may characterize the
      primary physiological responses to stress for both males and females, we propose
      that, behaviorally, females' responses are more marked by a pattern of "tend-and
      befriend." Tending involves nurturant activities designed to protect the self and
      offspring that promote safety and reduce distress; befriending is the creation
      and maintenance of social networks that may aid in this process. The
      biobehavioral mechanism that underlies the tend-and-befriend pattern appears to
      draw on the attachment-caregiving system, and neuroendocrine evidence from animal
      and human studies suggests that oxytocin, in conjunction with female reproductive
      hormones and endogenous opioid peptide mechanisms, may be at its core. This
      previously unexplored stress regulatory system has manifold implications for the
      study of stress.

PMID- 10941276
TI  - How the propagation of error through stochastic counters affects time
      discrimination and other psychophysical judgments.
AB  - The performance of fallible counters is investigated in the context of pacemaker
      counter models of interval timing. Failure to reliably transmit signals from one
      stage of a counter to the next generates periodicity in mean and variance of
      counts registered, with means power functions of input and standard deviations
      approximately proportional to the means (Weber's law). The transition diagrams
      and matrices of the counter are self-similar: Their eigenvalues have a fractal
      form and closely approximate Julia sets. The distributions of counts registered
      and of hitting times approximate Weibull densities, which provide the foundation
      for a signal-detection model of discrimination. Different schemes for weighting
      the values of each stage may be established by conditioning. As higher order
      stages of a cascade come on-line the veridicality of lower order stages degrades,
      leading to scale-invariance in error. The capacity of a counter is more likely to
      be limited by fallible transmission between stages than by a paucity of stages.
      Probabilities of successful transmission between stages of a binary counter
      around 0.98 yield predictions consistent with performance in temporal
      discrimination and production and with channel capacities for identification of
      unidimensional stimuli.

PMID- 10941278
TI  - Bias in proportion judgments: the cyclical power model.
AB  - When participants make part-whole proportion judgments, systematic bias is
      commonly observed. In some studies, small proportions are overestimated and large
      proportions underestimated; in other studies, the reverse pattern occurs.
      Sometimes the bias pattern repeats cyclically with a higher frequency (e.g.,
      overestimation of proportions less than .25 and between .5 and .75;
      underestimation otherwise). To account for the various bias patterns, a cyclical
      power model was derived from Stevens' power law. The model proposes that the
      amplitude of the bias pattern is determined by the Stevens exponent, beta (i.e.,
      the stimulus continuum being judged), and that the frequency of the pattern is
      determined by a choice of intermediate reference points in the stimulus. When
      beta < 1, an over-then-under pattern is predicted; when beta > 1, the under-then
      over pattern is predicted. Two experiments confirming the model's assumptions are
      described. A mixed-cycle version of the model is also proposed that predicts
      observed asymmetries in bias patterns when the set of reference points varies
      across trials.

PMID- 10941277
TI  - Discreteness and interactivity in spoken word production.
AB  - Five theories of spoken word production that differ along the discreteness
      interactivity dimension are evaluated. Specifically examined is the role that
      cascading activation, feedback, seriality, and interaction domains play in
      accounting for a set of fundamental observations derived from patterns of speech
      errors produced by normal and brain-damaged individuals. After reviewing the
      evidence from normal speech errors, case studies of 3 brain-damaged individuals
      with acquired naming deficits are presented. The patterns these individuals
      exhibit provide important constraints on theories of spoken naming. With the help
      of computer simulations of the 5 theories, the authors evaluate the extent to
      which the error patterns predicted by each theory conform with the empirical
      facts. The results support a theory of spoken word production that, although
      interactive, places important restrictions on the extent and locus of
      interactivity.

PMID- 10941279
TI  - Visual perception of dynamic properties: cue heuristics versus direct-perceptual
      competence.
AB  - Constructivist and Gibsonian approaches disagree over the possibility of direct
      perceptual use of advanced information. A trenchant instance concerns visual
      perception of underlying dynamic properties as specified by kinematic patterns of
      events. For the paradigmatic task of discrimination of relative mass in observed
      collisions, 2 mathematical models are developed, 1 model representing a direct,
      invariant-based approach, and 1 representing a cue-heuristic approach. The models
      enable a critical experimental design with distinct predictions concerning
      performance data and confidence ratings. Although pretraining results were mixed,
      the invariant-based model was empirically confirmed after a minimal amount of
      training: Competence entails the use of advanced kinematic information in a
      direct-perceptual ("sensory") mode of apprehension, in contrast to beginners' use
      of simpler cues in an inferential ("cognitive") mode.

PMID- 10941280
TI  - Gamma-range oscillations in backward-masking functions and their putative neural
      correlates.
AB  - Backward-masking functions have been hitherto categorized into two types,
      commonly named Type A and Type B. The analysis of a model of Retino-Cortical
      Dynamics produces the prediction that spatially localized stimuli should reveal
      an oscillatory metacontrast function. The predicted new type of metacontrast
      masking function was investigated in a psychophysical experiment. The results
      show oscillatory metacontrast functions with significant power in the gamma range
      (30-70 Hz). A marked decrease in the oscillations is observed when the spatial
      extent of the stimuli is increased. The theoretical basis of the study relates
      the oscillations found in the metacontrast function to gamma-range oscillations
      observed in scalp and intracerebral recordings. The qualitative agreement between
      the model and data provides support for this putative relationship.

PMID- 10941281
TI  - How experts' adaptations to representative task demands account for the expertise
      effect in memory recall: comment on Vicente and Wang (1998).
AB  - K. A. Ericsson and W. Kintsch's (1995) theoretical framework of long-term working
      memory (LTWM) accounts for how experts acquire encoding and retrieval mechanisms
      to adapt to real-time demands of working memory during representative
      interactions with their natural environments. The transfer of the same LTWM
      mechanisms is shown to account for the expertise effect in unrepresentative
      "contrived" memory tests. Therefore, K. J. Vicente and J. H. Wang's (1998)
      critique of the generalizability of the LTWM framework is rejected. Their
      proposed refutation of LTWM accounts is found to be based on misrepresented
      facts. The process-based framework of LTWM is shown to be superior to their
      product theory because it can explain interactions of the expertise effect in
      "contrived" recall under several testing conditions differing in presentation
      rate, instructions, and memory procedures.

PMID- 10941282
TI  - Expertise effects in memory recall: comment on Vicente and Wang (1998).
AB  - K. J. Vicente and J. H. Wang (1998) proposed a "constraint attunement hypothesis"
      to explain the large effects of domain expertise on memory recall observed in a
      number of task domains. They claimed to have found serious defects in alternative
      explanations of these effects, which their theory overcomes. Reexamination of the
      evidence shows that their theory is not novel but has been anticipated by those
      they criticized and that other current published theories of the phenomena do not
      have the defects that Vicente and Wang attributed to them. Vicente and Wang's
      views reflect underlying differences about (a) emphasis on performance versus
      process in psychology and (b) how theories and empirical knowledge interact and
      progress with the development of a science.

PMID- 10941283
TI  - Revisiting the constraint attunement hypothesis: reply to Ericsson, Patel, and
      Kintsch (2000) and Simon and Gobet (2000).
AB  - This article is part of an exchange concerning the contributions of the
      constraint attunement hypothesis (CAH) to the understanding of expertise effects
      in memory recall. K. A. Ericsson, V. Patel, and W. Kintsch (2000) and H. A. Simon
      and F. Gobet (2000) claim that the CAH is not novel and that existing theories of
      this phenomenon do not have the limitations that were attributed to them. In this
      reply, the CAH is argued to be the only theory of expertise effects in memory
      recall to adopt the abstraction hierarchy as a theory of the environment, a
      feature that has important theoretical implications. Also, other theories focus
      on psychological mechanisms but have not satisfied the burden of scientific proof
      required of process theories. Progress can be made by integrating the
      complementary advantages of existing theories into a unified theory that
      acknowledges the equally important roles of the organism and the environment.

PMID- 10941285
TI  - The role of computational models in neuropsychological investigations of
      language: reply to Ruml and Caramazza (2000).
AB  - W. Ruml and A. Caramazza's (2000) analysis of the model of normal and aphasic
      lexical access proposed by G. S. Dell, M. F. Schwartz, N. Martin, E. M. Saffran,
      and D. A. Gagnon (1997) is completely at odds with current practice concerning
      the use of models in psychology. An evaluation of Dell et al.'s original claims
      using Ruml and Caramazza's model parameters sustains these claims in all
      respects.

PMID- 10941284
TI  - An evaluation of a computational model of lexical access: comment on Dell et al.
      (1997).
AB  - The computational model of lexical access proposed by G. S. Dell, M. F. Schwartz,
      N. Martin, E. M. Saffran, and D. A. Gagnon (1997) is evaluated. They argued that
      fits of their model to naming data obtained from normal and brain-damaged
      patients support assumptions regarding interactivity in the lexicon, global
      damage in aphasia, and continuity between normal and aphasic naming behavior.
      Additional analysis reveals that the model fits the empirical data poorly and
      that the claims Dell et al. made on the basis of the model's performance would
      not follow even if the model were accurate. Although use of a novel automatic
      regression procedure improved the model's fit, it cannot account for 5 of Dell et
      al.'s 21 patients (24%), and its limitations were found to be inherent in its
      design. It is argued that claims such as those made by Dell et al. can only be
      addressed by considering evidence from multiple related tasks and by comparing
      multiple computational models.

PMID- 10941286
TI  - [Current neurological findings support psychosomatic assumptions].

PMID- 10941287
TI  - [Mental illness and physical disorders].
AB  - Close association between mental disorders, e.g. depressive or anxiety disorders,
      and numerous physical diseases has been consistently reported in clinical studies
      of patients with specific medical disorders, as well as among persons undergoing
      treatment for mental disorders. Accurate classification of this comorbidity has
      major implications for diagnosis, treatment, and course of both the psychological
      disorders and concomitant somatic diseases. The article summarises studies and
      reviews of comorbidity of mental disorders and selected somatic conditions
      (oncological, cardiovascular, endocrinological, and musculo-skeletal disorders).
      Methodological issues, risk factors, possible mechanisms of comorbidity, and
      implications of these associations for diagnosis, treatment, and planning of
      future studies are described.

PMID- 10941288
TI  - [Are the children of fatherless families more frequently emotionally disturbed in
      adult life?].
AB  - It has been the subject of numerous debates recently whether children who grew up
      without fathers suffer more than others under the long-term consequences of their
      fatherless childhood. In 1994 we conducted a large-scale population-based
      investigation over a hundred subjects who had grown up without father to
      establish standardized norms for various psychometric questionnaires that were
      also relevant to this issue. This allows us to contribute to the discussion with
      some concrete data, which correspond without exception with the dominant trend of
      other research results. Whereas there was evidence to support the view that some
      children of fatherless families do indeed suffer from increased emotional
      disturbance in later life, there were also indications that others even profited
      emotionally from their fatherless childhood. In the area of bodily complaints the
      results were confounded to a high degree with gender differences, showing that
      women are more frequently negatively affected, and men more positively.

PMID- 10941289
TI  - [Therapeutic goals and indications: psychotherapy patient's self-reports during
      diagnostic assessment].
AB  - Although individual therapeutic goals are considered to be important factors
      motivating patients to engage in therapeutic work, they have gained little
      attention in empirical research. In the present study, patients were given a
      questionnaire containing 24 therapeutic goals which could be rated according to
      their subjective relevance on a 5-point scale. N = 152 patients (mean age 34.5
      years, 59.2% female) who presented at a university psychotherapy outpatient
      department to attend a diagnostic interview participated in the study. "To solve
      my problems" and "to get relief from my complaints" were the goals that were
      rated as most important. Goals pertaining to mental health such as more
      contentness and calmness, self-assertion and insight scored high, too. Three
      rational scales were constructed: 1. insight, 2. sociability, and 3. self
      assertion. These scales were correlated with both patients' causal attributions
      and therapy expectations in plausible ways. However, the general strength of
      intercorrelations point of the conception patients goals were not very succinct
      at the time of the intake interview. Indication groups regarding specific
      therapeutic measures did not differ with respect to therapy goals. Only the
      general decision whether to recommend a psychotherapeutic intervention or not
      seemed to be influenced by patients' therapeutic aims.

PMID- 10941290
TI  - [Illness behavior and expectations on physician-patient relationships of medical
      students in the second and fifth year of education].
AB  - We investigated illness behaviour and treatment expectations of future
      physicians. 209 medical students in their second and 110 students in their fifth
      year of education were examined by means of a specific questionnaire and the
      Biographic Inventory for Diagnosis of Abnormal Behaviour (BIV). As to our
      questionnaire we found a six factors solution that could explain 44% of the
      variance. Students in the fifth year of education were more critical towards
      physicians, waited longer until they took advantage of professional help, tried
      more to influence both the diagnostic and therapeutic process and they adhered
      stronger to a psychosocial concept of illness than the second year students.
      Women desired more psychological support and fell back on household remedies more
      often than men. Students who had experienced a poor parent-child-relationship
      also were dissatisfied with their physician-patient-relationship. Introverted
      students were less demanding towards their physicians and more often searched for
      help in the lay system than extroverted students. With these factors, behaviour,
      experiences and attitudes of medical students with reference to a potential or
      actual patient role can be well described.

PMID- 10941291
TI  - [Treatment for asthma and international recommendations].
AB  - This is a short review of current "asthma guidelines". It is an opportunity to
      discuss briefly the pro and cons of the guidelines as such, and also of the
      Evidence-Based Medicine (EBM), as well as the links between guidelines and EBM.
      We try to define what are the guidelines and what they are not.

PMID- 10941292
TI  - [Chronic obstructive pulmonary disease (COPD) and international guidelines].
AB  - This is a short summary of the present situation of the guidelines about the
      diagnosis, management and treatment of COPD. Some insights on the future GOLD
      guidelines to be published during this year are presented, as well as some
      possible future treatments to come, according to some articles concerning
      promising new drugs.

PMID- 10941293
TI  - [Evidence-based medicine: treatment of chronic hepatitis C. Liege Study Group on
      Viral Hepatitis].
AB  - The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The
      major characteristic of virus C is its tendency to chronicity in more than 85% of
      cases. Generally asymptomatic, HCV infection may also evolve with time to
      cirrhosis and hepatocellular carcinoma. During the last few years, HCV-related
      end-stage cirrhosis has become the first cause of liver transplantation. In 10
      years only, very significant progress has been made in the knowledge of the
      virus, not only in the field of diagnosis but also in therapy. Several consensus
      conferences taking last discoveries into account have been organized in order to
      promote recommendations useful for the management of hepatitis C patients. The
      aim of this short overview is to summarize practical recommendations that emerged
      recently from consensus meetings.

PMID- 10941294
TI  - [Gastroesophageal reflux in the adult: diagnosis and treatment].
AB  - Gastro-oesophageal reflux is a frequent problem affecting up to one third of the
      Belgian adult population. It is most often a benign non evolutive disease. It is
      however frequently chronic, with a significant negative impact on quality of
      life. The diagnostic and therapeutic management must be adapted to each
      individual case. In the majority of cases, the purpose of therapy is the control
      of symptoms and, in a small number of cases with severe oesophagitis the aim is a
      complete and persistent healing of lesions. A Franco-Belgian consensus meeting on
      diagnostic and therapeutic management of gastro-oesophageal reflux disease in
      adults was recently held. Guidelines have been proposed. The aim of the present
      paper is to highlight the main principles of these guidelines and to comment on
      their adjustment to current belgian medical practice.

PMID- 10941295
TI  - [Guidelines for the management of Helicobacter pylori: recent opinion of the
      French National Society of Gastroenterology].
AB  - Guidelines for management of Helicobacter pylori are in constant evolution since
      its discovery in 1982 by Marshall and Warren. This article presents and comments
      recent guidelines developed under the auspices of the "Societe Nationale
      Francaise de Gastroenterologie".

PMID- 10941296
TI  - [Guidelines concerning the treatment of rectal cancer].
AB  - Curative resection of primary tumor and metastases is the only way to obtain a
      prolonged survival. Several additional treatments are under evaluation; some are
      already routinely proposed, in order to reduce the tumor size and to allow
      surgery, to reduce the recurrence rate, and to give a better survival in case of
      unresectable metastases. Even in case of unresectable metastases, resection of
      the primary tumor should be envisaged, as quality of life with an evolving rectal
      tumor is very poor.

PMID- 10941297
TI  - [Adjuvant treatment of breast cancer: meta-analysis and therapeutic
      recommendations].
AB  - Adjuvant chemotherapy and hormonotherapy have a major impact on relapse-free and
      overall survival of patients with early-stage breast cancer. Providing effective
      medical care for these patients is an important public health issue. We reviewed
      the results of the meta-analysis performed by the "Early Breast Cancer Trialists'
      Cooperative Group". We summarize the recommendations and guidelines proposed by
      the International Consensus Panel during the St Gallen Conference, 1998. We
      discussed also the methodology used by the "Federation National des Centres de
      Lutte Contre le Cancer" in France to establish guidelines for the adjuvant
      treatment of breast cancer. Faster development and validation of effective
      treatments will only be possible if participation in clinical trials become more
      acceptable to the public as well as to the medical community.

PMID- 10941298
TI  - [Recommendations of the Belgian Lipid Club for the diagnosis and treatment of
      hyperlipidemias: summary for the practitioner].
AB  - The present paper summarizes the last recommendations of the Belgian Lipid Club
      for the diagnosis and treatment of hyperlipidaemias which were published in 1999.
      These guidelines are in agreement with the "Recommendations of the second Task
      Force of European and other societies on Coronary Protection", published in 1998.
      We will briefly describe the evidence supporting the treatment of dyslipidaemias,
      especially hypercholesterolaemia, to improve coronary prognosis of at high risk
      subjects as well as the general strategies, lipid objectives and therapeutic
      means, in a practical way for the clinician.

PMID- 10941299
TI  - [Recommendations for the treatment of obesity].
AB  - Obesity represents a major medical problem which is now considered more seriously
      from a scientific, clinical and economical point of view. Such an evolution was
      mandatory when considering the usual contempt for what is now considered as a
      chronic disease and especially the charlatanism which was observed among medical
      and non-medical spheres. Hence, as for numerous other pathologies, international
      guidelines have recently been published to optimize the management of obesity,
      from the view point of efficacy and, more particularly, safety. We will summarize
      the main recommendations as far as diet and physical treatment, pharmacotherapy
      and bariatric surgery are concerned. Finally, we will briefly describe general
      guidelines on the management of obese subjects taking into account the degree of
      weight excess and the presence of complications.

PMID- 10941300
TI  - [GLycemic control in the diabetic patient. Recommendations after the DCCT and
      UKPDI studies].
AB  - Diabetes mellitus is a chronic disorder characterized by microvascular and
      cardiovascular complications that substantially increase the morbidity and
      mortality associated with the disease. Several studies showed the association
      between the complications of diabetes and elevated blood glucose levels. Clinical
      trials have also demonstrated that treatment that lowers blood glucose reduces
      the risks of diabetic complications (mainly microvascular complications). The
      control of diabetes is assessed by frequent measurements of HbA1c. A reasonable
      goal in type 1 diabetes is a value of HbA1c < or = 7.2%. In type 2 diabetes, the
      optimal goal is a value of HbA1c < or = 6.5%, but a value < or = 8% seems to be
      an acceptable goal in these patients.

PMID- 10941301
TI  - [Guidelines for the treatment of arterial hypertension in diabetic patients].
AB  - Diabetes mellitus is frequently associated with arterial hypertension and the
      combination of the two entities markedly increases the cardiovascular risk and
      accelerates the progression of microangiopathy (more particularly nephropathy) in
      both type 1 and type 2 diabetic patients. Numerous international guidelines have
      been published during the last few years to help the practitioner in targeting
      ideal arterial blood pressure levels (lower in diabetic than in non-diabetic
      patients) and in selecting first-choice antihypertensive agents. We will
      concisely summarize the main messages of these recommendations and insist upon
      the persistence of uncertainties, or even the existence of inconsistencies, more
      particularly regarding preferential indications of antihypertensive agents in
      diabetic patients.

PMID- 10941302
TI  - [Chronic renal failure: management suggestions based on scientific evidence].
AB  - Chronic renal failure whatever its etiology is a progressive disease, associated
      with important morbidity and mortality. Most patients will require renal
      replacement therapies (hemodialysis, peritoneal dialysis or transplantation). An
      early follow up by nephrologists, an optimal control of hypertension and of the
      glomerular hyperfiltration syndrome, might allow slowing the rate of evolution of
      nephropathies. At least, this approach allows to delay complications of renal
      failure and to improve the patient survival. Guidelines based on scientific
      studies are presently available to approach the treatment of chronic renal
      failure.

PMID- 10941303
TI  - [Guidelines for the treatment of depression].
AB  - Depression is a common psychiatric disorder with a lifetime prevalence estimated
      of 17%. About 25% of the patients develop chronic depression. Diagnosis and
      treatment are not easy to establish. The authors summarize the latest data on
      this topic, and suggest Guidelines based upon Consensus Conferences and Evidence
      Based Medicine.

PMID- 10941304
TI  - [Guidelines for the treatment of alcoholism].
AB  - Alcoholism is a chronic disorder that results from genetic, psychosocial and
      environmental factors. General practitioners who provide continuous care can have
      a major role in the follow-up of patients with alcohol-related problems, by
      providing screening and assessment, patient education and referral to a
      specialist if indicated. Treatment of alcohol-dependence now benefits from clear
      guidelines. The authors summarize the latest data in this field.

PMID- 10941305
TI  - [Guidelines for the treatment of anxiety disorders in adults].
AB  - The treatment of anxiety disorders has considerably improved and become more
      precise over the last two decades, on the basis of empirical results. The
      evidence of their efficacy is best established for panic disorder, obsessive
      compulsive disorder and social phobia. The pharmacological treatment and the
      psychotherapeutical approaches of these three categories will be briefly
      reviewed, using data from well conceived studies and recommendations of experts.
      Thus, for each of these disorders, this article attempts to provide the physician
      with practical treatment guidelines.

PMID- 10941306
TI  - [Guidelines for the treatment of opiate addiction].
AB  - Over the past 20 years, scientific progress have revolutionised our understanding
      of the nature of opiate addiction and its various possible treatments. Addiction
      is a chronic illness treatable if the treatment is well-delivered and tailored to
      the needs of the particular patient. There is indeed an array of treatments that
      can effectively reduce drug use, help manage drug cravings, prevent relapses and
      restore people to productive social functioning. The treatment of drug addiction
      will be part of a long-term, medical, psychological and social perspective.

PMID- 10941307
TI  - [Guidelines for the management of patients with HIV infection. I. Adolescents and
      adults. Liege Working Group on HIV Infection].
AB  - The management of HIV infected patient requires an approach that must put in
      balance profits expected from a tritherapy (suppression of viral replication,
      immune reconstitution) and problems related to treatment (difficulty of
      adherence, side effects, long-term toxicity, resistance). Controversies appear
      currently on the institution of a precocious treatment, on the use of protease
      inhibitors at initiation, in order to preserve choices when a modification is
      necessary. Many concepts, in investigation, are described in the management of a
      therapeutic failure. Resistance testings progressively find their place in the
      follow-up. Modes of prophylaxis-interruption of opportunistic infections are
      established, as well as is the management of professional postexposure. The
      question remains on how best to advise seropositive couples, about conception,
      and to elaborate recommendations after non-professional postexposure.

PMID- 10941308
TI  - [Guidelines for the management of patients with HIV infection. II. Pregnant women
      and children. Liege Working Group on HIV Infection].
AB  - The management of the HIV infected child is nearly identical to the adult.
      Nevertheless, there are many clinical, immunological and virological details.
      Difficulties evoked for the adult have an even bigger importance, in view of the
      foreseeable longevity of these children under treatment. The reduction of the
      mother to child transmission, thanks to the AZT-caesarean association, must be
      continued. The use of anti-retroviral drugs during pregnancy requires a sustained
      attention because of the potential risks and benefits for the foetus and mother.
      The long-term impact of these drugs, in children exposed during pregnancy,
      remains unknown. The follow-up of these children therefore remains important.

PMID- 10941309
TI  - [Factual approach to the treatment of genital herpes].
AB  - Genital herpes is a sexually transmitted disease. After the primary infection,
      the virus establishes a life-long latency in the sacral dorsal root ganglia.
      Recurrences may occur at an unpredictable rate. The clinical signs are not always
      easy to recognize and viral identification techniques may be helpful such as
      immunohistochemistry and in situ hybridization on Tzanck smears and muco
      cutaneous biopsies. The treatment of genital herpes can follow one of three
      strategies using antiviral drugs, non-specific immunomodulators, and vaccination.
      The new oral antiviral drugs decrease the severity of clinical manifestations
      without, however, providing a definitive cure. In this article recent knowledge
      about the clinical aspects, differential diagnosis, diagnostic methods, treatment
      options and management is reviewed.

PMID- 10941310
TI  - [Why should we treat onychomycosis with patience and perseverance? How can we
      overcome therapeutic failure?].
AB  - Antifungal treatments for onychomycoses may be long and expensive without,
      however, affording the guarantee of success. A review of the literature reveals
      that the current topical treatments and the oral intake of fluconazole are of
      long duration. They show moderate clinical efficacy and/or a pharmaco-economic
      profile less favorable than those of intermittent itraconazole therapy and
      terbinafine continuous therapy. Between the latter two options, itraconazole has
      some advantages because of its broad spectrum of activity against diverse types
      of fungi responsible for onychomycoses. The fungicidal activity of terbinafine
      exhibited in vitro cannot unfortunately be claimed in the in vivo situation when
      treating a patient. Some interactions exist between these antifungals and a few
      other drugs. Other side effects are rare and usually discrete and reversible.

PMID- 10941311
TI  - [Involutional osteoporosis in women: therapeutic strategy. Recommendations of the
      Belgian Bone Club].
AB  - Osteoporosis is now considered as a major public health issue and a serious
      threat for the quality of life of elderly women. Several new compounds are
      currently marketed for the prevention and treatment of involutional osteoporosis
      in women. Therefore, it is important to offer to the practitioners pragmatic
      solutions to be used for the rational management of this disorder. This article
      is the result of a national consensus offering practical guidelines for the
      management of osteoporotic patients, based on the current published data.

PMID- 10941312
TI  - [Towards a consensus regarding androgen substitution therapy for andropause].
AB  - "Andropause" or "male climateric" refer to the term "menopause" in the women. The
      parallelism between both entities is however only partial since the decrease of
      gonadal function in the male is very different from one individual to the other.
      Some men present a gonadal deficiency together with an increase gonadotropin
      function as early as in the 40s while others show normal testicular function at
      80 or later! It appears that besides genetic factors many life events (stress,
      obesity, sedentarity...) can "precipitate" testicular failure. Besides the major
      symptoms of sexual impotency and loss of libido, testosterone deficiency also
      induces reversible modification in lipid profile, muscle strength, bone density
      ... and on some cognitive and psychological parameters. It is therefore
      reasonable to treat androgen deficiency in early or late aging provided a
      cautious urological check-up has been realized before treatment. The mode of
      administration (i.m., p.o., or transdermal) will depend on the principal goal of
      the treatment and on the wish of the patient! An annual clinical and biological
      urological assessment is mandatory.

PMID- 10941313
TI  - [Consensus on the clinical approach to erectile dysfunction in patients with
      cardiovascular disease].
AB  - The most common physical risk factors for erectile dysfunction (ED) are
      atherosclerosis, heart disease, hypertension and diabetes. Since accessibility to
      easy and efficacy drug for ED therapy, GPs are increasingly at the front line in
      the management of ED and are often best-placed to discuss this problem with
      cardiovascular male patients. This consensus aims to provide practical advice on
      the management of ED in patients with diagnosed cardiovascular disease and also
      addresses the assessment of the cardiovascular risk in restoring sexual activity
      in these patients. A risk assessment algorithm has been drawn up to aid
      clinicians in deciding the level of cardiovascular risk that would be associated
      with a return of sexual activity as well as criteria for referral to specialists
      for further cardiac evaluation. Treatment options are briefly reviewed and follow
      up process identified.

PMID- 10941314
TI  - [Initiation and discontinuation of antiepileptic treatment].
AB  - The actual decision regarding whether or not to treat a patient presenting a
      first seizure must be individualized, considering both the probability of a
      recurrence, and the perceived risks/benefits ratio of the treatment. The latter
      depends on the physician's assessment of the potential morbidity of another
      seizure versus the potential morbidity of antiepileptic drug therapy. In many
      situations, there is no single correct answer to the question "Should this
      patient be treated?". The same evaluation of the potential risks and benefit of
      stopping the treatment arises again when the patient has been seizure-free for a
      sufficient period of time. The patient must be informed of the pros and cons and
      should always be associated with the decision.

PMID- 10941315
TI  - [The non-recommendations in the treatment of osteoarthritis and rheumatoid
      arthritis, or why is evidence-based medicine so difficult (still) to apply to
      rheumatology?].
AB  - The speed with which the phrase "Evidence-Based Medicine" has entered our
      language has been astonishing. Virtually all medical areas are concerned, but it
      probably applies best when clearcut diagnosis can be made or when mortality or
      well-defined morbidity are the outcomes, two conditions not really frequently
      encountered in rheumatology. We will discuss why rheumatology is probably not
      ready yet for the concept and will systematically review why "Evidence-Based
      Medicine" could in fact be "evidence-biased medicine". We will emphasize why
      evidence-based medicine can not replace the personal experience and knowledge of
      patients, two major corner-stones in the clinician's daily work, but should
      simply be an access to scientific data for the benefit of both patient and
      physician.

PMID- 10941316
TI  - [On evidence-based medicine and therapy recommendations. Epilogue].

PMID- 10941317
TI  - Breastfeeding--a gradual return to mother's autonomy.
AB  - The aim of this study, the final in a series, was to assess mothers' perceptions
      of some aspects of midwifery care in relation to breastfeeding. These included
      conflicting advice and its possible effect on breastfeeding outcomes; whether
      information considered crucial to the maintenance of breastfeeding was provided
      by health professionals; and whether mother's autonomy was encouraged following
      the implementation of antenatal breastfeeding workshops. A structured, self
      administered questionnaire was mailed to 550 women who delivered in 1994
      approximately one year after the birth of their child. The results obtained were
      compared to those achieved in a 1991 survey of a similar population. Of the 247
      respondents, 33.5% considered they had received conflicting advice, with 18.6%
      commenting they felt this had negatively influenced how successfully they had
      breastfed. Three quarters of the women surveyed indicated they received
      information on the factors considered crucial for the maintenance of lactation.
      Seventy-eight percent (78%) said they usually or always attached the baby for
      themselves. Fifty-three percent (53%) of the mothers breastfed for more than six
      months, and 37.7% were still breastfeeding at 12 months.

PMID- 10941318
TI  - The counselling needs of breastfeeding women.
AB  - The aim of this study was to identify the needs of a sample of 1520 people who
      contacted Nursing Mothers' Association of Australia (NMAA) Breastfeeding
      Counsellors for help during the week 19 to 25 October 1998. The majority (98.8%)
      of those who made contact with NMAA Counsellors were mothers or expectant
      mothers. Mothers of babies in the birth-to-three-month age bracket accounted for
      more than half (51.1%) of all counselling contacts. The five greatest areas of
      need for those who sought help from NMAA Counsellors were reassurance (58.6%),
      feed frequency (26.5%), positioning and attachment (18.1%), looking after
      yourself (16.3%) and fatigue/tiredness (15.3%).

PMID- 10941319
TI  - Breastfeeding and Chinese mothers living in Australia.
AB  - This study sought information on the breastfeeding rates, knowledge and beliefs
      of 101 migrant Chinese mothers living in south-west Sydney. Differences in
      beliefs about breastfeeding and bottle-feeding practices between migrant and
      indigenous groups of mothers were also examined. Sixty-five percent of Chinese
      mothers were fully breastfeeding their infants on discharge, with a further 6.9%
      partially breastfeeding. However, only 34% were still breastfeeding at three
      months. The most important factor to influence mothers' choice to breastfeed was
      the belief that it was 'good for the baby', whilst mothers choosing to bottle
      feed were influenced by low milk supply and the belief that it was easier.
      Similar beliefs about breastfeeding and bottle-feeding were held by indigenous
      and migrant Chinese mothers, although concerns about the baby becoming too
      attached were markedly higher in the migrant group and may be related to sudden
      drops in breastfeeding rates at three months. Focusing ethno-specific services
      upon continuation of breastfeeding throughout the first six months of the
      infant's life is recommended, with a Chinese mothers' breastfeeding support
      network being posed as a possible approach.

PMID- 10941320
TI  - Impetigo on the areola and nipple.

PMID- 10941321
TI  - Heart rate variability, mortality, and exercise in patients with end-stage renal
      disease.
AB  - CONTEXT: Cardiac autonomic function has been associated with mortality in
      patients with end-stage renal disease. It is unknown whether end-stage renal
      disease patients who have succumbed to sudden cardiac death can be better
      identified by a newer test of heart rate variability that uses spectral analysis,
      rather than laboratory evoked measures. OBJECTIVE: This series of studies sought
      to characterize cardiac autonomic function in patients awaiting kidney
      transplantation, identify factors associated with heart rate variability,
      identify tests which distinguish patients at-risk for death, and compare evoked
      measures with 24-hour heart rate variability measures. PATIENTS: Data were
      collected on 184 nondiabetics, 60 type 1 diabetics, and 34 type 2 diabetics with
      end-stage renal disease, all of whom had been referred for kidney
      transplantation. MAIN OUTCOME MEASURES: The 278 patients and 67 healthy control
      subjects underwent evoked tests (changes in heart rate with deep breathing and
      Valsalva maneuver) and 24-hour heart rate variability Holter monitoring (time and
      frequency domains). Five patients had sudden cardiac deaths during the study.
      RESULTS: Data showed that end-stage renal disease patients, particularly
      diabetics, had compromised autonomic function. The standard deviation of all R-to
      R intervals for the electrocardiogram recording (< 50 minutes in 60% of the
      deceased patients), a 24-hour heart rate variability time domain measure, holds
      the promise of identifying patients at increased risk for death. Exercise was
      identified as a factor associated with better autonomic function. Examining
      relationships between 24-hour heart rate variability and characteristics of
      patients who succumb to death could make quantification of the mortality risk for
      individual pretransplant end-stage renal disease patients possible, much as it
      has in other populations. The data from this study may also make it possible to
      design interventions, such as exercise, aimed at reducing mortality risk.

PMID- 10941322
TI  - Left internal mammary artery graft retransplantation from the recipient to the
      donor heart: a case report.
AB  - A case of heart transplantation with concomitant coronary artery bypass graft is
      reported. The patient was an alternate transplant list candidate with a history
      of bilateral below-knee amputation and 2 previous myocardial revascularization
      procedures. The previously used and patent left internal mammary artery graft was
      successfully removed and retransplanted from the recipient to the donor heart.

PMID- 10941323
TI  - The role of daclizumab in balancing resources for inpatient and outpatient
      transplant services.
AB  - Transplant professionals have the dual responsibility of achieving acceptable
      clinical outcomes and controlling costs. One approach transplant centers have
      used to control transplant-related costs has been to decrease patients' length of
      stay, and thus it has decreased significantly in the last 6 years. This reduction
      in resource consumption has been accomplished by increased efficiency in
      providing transplantation services, expanding the number of outpatient services
      available, and integrating new technologies. Future cost containment measures by
      payers, especially Medicare, will continue to require that transplant centers
      manage resources and meet financial objectives while achieving acceptable
      clinical outcomes. Daclizumab, a new immunosuppressive drug, is used as an
      example in this article, which assesses its value in helping meet resource
      management and financial goals.

PMID- 10941324
TI  - Management of variations in blood pressure during care of organ donors.
AB  - The organ procurement coordinator commonly must correct and maintain the arterial
      blood pressure during donor care. This article reviews considerations in the
      accurate measurement of the blood pressure, causes of hypertension and
      hypotension, and desirable standards to use in order to provide adequate organ
      perfusion. Recommendations are presented for treatment of hypotension in a
      titrated response of intravenous fluids, inotropic support, and vasopressor
      infusion to maintain the mean arterial pressure above 65 mm Hg. Collaborative
      interaction between the coordinator and physician consultant remains important
      throughout management of blood pressure changes during donor care.

PMID- 10941325
TI  - Recommendations for mechanical ventilation during donor care.
AB  - The organ procurement coordinator usually directs adjustments to the mechanical
      ventilator during donor care. It is often difficult to achieve optimal oxygen
      uptake and carbon dioxide removal while avoiding barotrauma or undesirable
      effects on the cardiac output. Interrelationships among a variety of ventilator
      parameters must be understood in order to achieve the desired goal of providing
      the best organs possible. These recommendations review the key ventilator
      parameters of tidal volume; positive end-expiratory pressure; auto-positive end
      expiratory pressure; fraction of inspired oxygen; and flowrate and frequency and
      their interactions in controlling peak, plateau, and mean and end-expiratory
      airway pressures.

PMID- 10941326
TI  - Use of an HBV-DNA hybridization assay in the evaluation of equivocal hepatitis B
      virus tests in solid organ donors.
AB  - CONTEXT: Serological markers for the hepatitis B virus are routinely used in the
      evaluation of potential organ donors. However, serological tests can be
      associated with significant false or equivocal results and may not be indicative
      of the true risk of hepatitis B infection. Studies have recently questioned the
      significance of an isolated hepatitis B core antibody test in evaluating the
      suitability of solid organs for transplantation. The ability to detect hepatitis
      B virus DNA may prove useful when the diagnosis of hepatitis B infection is in
      doubt. DESIGN: Serum samples from 16 donors with equivocal or positive hepatitis
      B core antibody and/or hepatitis B surface antigen serological screening tests
      were retrospectively tested for the presence of hepatitis B DNA. Any available
      follow-up data on the placement of organs from these donors was obtained.
      RESULTS: One of the 16 (6.3%) donors tested positive for the presence of
      hepatitis B DNA, but organs from this donor were not recovered or transplanted.
      Follow-up on 14 organs recovered and transplanted from 6 donors in this group did
      not show clinical and/or laboratory evidence of hepatitis B infection in the
      recipients. CONCLUSIONS: In our donor population, there was a low incidence
      (6.3%) of donors with equivocal or positive hepatitis B core antibody and/or
      hepatitis B surface antigen serological screening tests who subsequently
      demonstrated the presence of detectable hepatitis B DNA. Posttransplantation
      follow-up of the recipients of 14 recovered organs failed to demonstrate any
      cases of posttransplant hepatitis B infection.

PMID- 10941327
TI  - Fears and concerns expressed by families in the donation discussion.
AB  - Previous research has identified specific fears and concerns among the general
      public about organ and tissue donation. However, little to none of that research
      has dealt with fears and concerns at the time of the donation discussion. In this
      study, 180 experienced coordinators ranked the fears and concerns most commonly
      heard during the donation discussion. They further classified the fears and
      concerns according to the ease with which they can be addressed. Subsequently,
      the fears and concerns were classified in 4 groups: often heard and easy to deal
      with, often heard and hard to deal with, seldom heard and easy to deal with,
      seldom heard and hard to deal with. The results can be used to stimulate further
      research on family fears and concerns, to train and retrain coordinators to
      address those concerns in the donation discussion, and to improve existing
      strategies for increasing organ and tissue donation.

PMID- 10941328
TI  - Improving public awareness of organ transplantation in Japan.
AB  - The goals of the Japanese chapter of the Transplant Recipients International
      Organization are to act as a mediator in the provision of mutual aid to
      transplant recipients, candidates, and their families and to provide education in
      both the public and professional arenas to promote organ transplantation in
      Japan. Since 1991, members of the Japanese chapter of the Transplant Recipients
      International Organization have acted as volunteer facilitators for more than 150
      transplant candidates and recipients. The organization's activities have included
      fund-raising to cover the costs of transplantation, preparing an original donor
      card for distribution, and petitioning members of the Diet (the Japanese
      legislative body) 14 times, including speaking at public hearings twice and
      submitting a petition requesting early passage of the organ transplant bill. The
      Japanese Diet finally passed an organ transplant bill in June 1997. The
      activities of the Japanese chapter of the Transplant Recipients International
      Organization have contributed to the promotion of organ transplantation in Japan
      and to understanding and support for transplantation within the Japanese
      community as a whole.

PMID- 10941329
TI  - Organ donation and transplantation as health programs in Italy.
AB  - Organ and tissue donation and transplantation have a role in public health
      programs as organizational projects designed by public health departments to
      increase the quality and number of donations and transplantations. These programs
      serve as communication projects to inform public opinion on cerebral death, organ
      and tissue shortages, procurement and allocation rules, and the quality of life
      of transplanted patients. The health department of Emilia-Romagna created a
      regional law and a multimedia communication program for these purposes, resulting
      in a 95% increase of cadaver donor in 4 years. In 1995, regional activity reached
      the European mean level and afterwards surpassed it. In 1997, the bone bank was
      activated, followed in 1998 by the heart valve and vascular segment bank. The
      regional health department now considers transplant activities a primary goal;
      human and professional relations between intensive care units and the transplant
      reference center are considered crucial; cooperation among health departments,
      medical teams involved in organ procurement and transplant activities has been
      fostered, and the local coordination network has been active and efficient. The
      public information campaign has proven important in providing information both to
      professionals and citizens.

PMID- 10941330
TI  - Lung cancer cytology. Something old, something new.

PMID- 10941331
TI  - Positive and negative interference of the Chinese medicine Chan Su in serum
      digoxin measurement. Elimination of interference by using a monoclonal
      chemiluminescent digoxin assay or monitoring free digoxin concentration.
AB  - An over-the-counter Chinese medicine, Chan Su, is used as a cardiotonic agent. We
      demonstrated significant digoxin-like immunoreactivity in various organic and
      aqueous extracts of Chan Su. For example, when a 20-microL aliquot of an aqueous
      extract of Chan Su powder (1 mg/mL) was added to a 2-mL aliquot of a drug-free
      serum, the observed digoxin-like immunoreactivity was 2.76 ng/mL (3.53 nmol/L)
      digoxin equivalent using the fluorescence polarization immunoassay (FPIA). The
      magnitude of interference was much lower (0.94 ng/mL [1.20 nmol/L]) with the
      microparticle enzyme immunoassay (MEIA), and no interference was observed with
      the chemiluminescent assay (CLIA). We also observed a significant positive
      interference of the extract with the serum digoxin measurement using FPIA. In
      contrast, we observed a negative interference (falsely lowered digoxin
      concentration) of the extract in the serum digoxin measurement with the MEIA. The
      extract had no effect on the serum digoxin measurement with the CLIA. By taking
      advantage of the high protein binding of Chan Su and only 25% protein binding of
      digoxin, we further demonstrated that positive interference of Chan Su in the
      FPIA and negative interference of Chan Su in the MEIA of digoxin could be
      eliminated by monitoring the free digoxin concentration.

PMID- 10941332
TI  - Performance characteristics of the COBAS AMPLICOR hepatitis C virus MONITOR Test,
      version 2.0.
AB  - We evaluated the performance characteristics of the COBAS AMPLICOR Hepatitis C
      Virus (HCV) MONITOR Test, version 2.0. Dilution studies using patient specimens
      demonstrated a lower limit of detection of 1,000 copies per milliliter. The assay
      was linear from 1,000 to 1 million HCV RNA copies per milliliter. Within-run
      precision and between-run precision were acceptable (approximately 0.100 and 0.14
      SD for log10 [copies per milliliter]). A comparison of this version of the test
      (y), with the manual AMPLICOR HCV MONITOR Test, version 1.0 (x), yielded the
      following Deming regression equation: y = 1.004(+/- 0.04)x + 0.654(+/- 0.22);
      Sy/x?D = 0.336; n = 92; r2 = 0.846; r = 0.920. Further comparison of the COBAS
      version 2.0 assay (x) with the QUANTIPLEX HCV bDNA Test (y) yielded the following
      Deming regression equation: y = 0.943 (+/- 0.130)x + 0.473 (+/- 0.717); Sy/x?D =
      0.194; n = 26; r2 = 0.600; r = 0.774. Version 2.0 detected the spectrum of HCV
      genotypes better than version 1.0.

PMID- 10941333
TI  - Cytokeratin 8 immunostaining pattern and E-cadherin expression distinguish
      lobular from ductal breast carcinoma.
AB  - Immunohistochemistry using antibodies to cytokeratin 8 can serve as a valuable
      diagnostic tool for the differentiation of lobular from ductal carcinomas of the
      breast. In contrast with ductal carcinomas, which exhibit a peripheral
      predominant immunostaining pattern, adjacent tumor cells "molding" to each other,
      lobular carcinomas exhibit a ring-like perinuclear immunostaining pattern,
      creating a "bag of marbles" appearance with neighboring tumor cells. This
      immunostaining pattern is stable even in the tumors that otherwise do not exhibit
      characteristic histomorphologic features (i.e., solid or pleomorphic type of a
      lobular carcinoma) and tumors that mimic growth patterns characteristic of the
      respective other tumor type (i.e., targetoid or single-file growth pattern in a
      ductal carcinoma). Furthermore, we demonstrate that ductal carcinomas express E
      cadherin in a similar peripheral-predominant immunostaining pattern (33/33
      cases), while all 15 lobular carcinomas were negative for E-cadherin, suggesting
      a role for E-cadherin in the architectural organization of the cytoskeletal
      scaffolding within the tumor cells.

PMID- 10941334
TI  - Cytologic features useful for distinguishing small cell from non-small cell
      carcinoma in bronchial brush and wash specimens.
AB  - One blinded observer (C.D.S.) retrospectively reviewed 76 previously diagnosed
      and biopsy-confirmed malignant bronchial brush and wash specimens, 46 non-small
      cell and 30 small cell carcinomas, obtained from 55 patients. Each case was
      scored for the presence or absence of 36 standard criteria (architectural,
      cytoplasmic, and nuclear). Logistic regression analysis was used to determine
      which criteria were most useful for separating small cell from non-small cell
      lesions. Although no single criterion displayed 100% sensitivity and specificity
      for small cell cancer, univariate statistical analysis indicated that 3
      individual criteria (nuclear molding, finely granular or "salt and pepper"
      chromatin, and scant delicate cytoplasm) were more than 90% sensitive and
      specific in cases of small cell carcinoma. The presence of nuclear molding alone
      provided the best fit for the logistic regression model. When nuclear molding was
      present, the odds of a small cell diagnosis increased more than 300-fold. Nuclear
      molding, finely granular or salt and pepper chromatin, and scant, delicate
      cytoplasm are the 3 most sensitive and specific cytomorphologic features
      traditionally used to separate small cell from non-small cell carcinoma. Nuclear
      molding alone represents the most significant cytomorphologic feature for
      distinguishing between these malignant lesions.

PMID- 10941335
TI  - An optimized battery of eight antibodies that can distinguish most cases of
      epithelial mesothelioma from adenocarcinoma.
AB  - An immunocytochemical battery comprising 9 antibodies specifically distinguishes
      80% of the epithelial malignant mesotheliomas from adenocarcinomas. The
      discriminatory power of antibodies to calretinin was tested together with this
      battery to determine whether the performance thereby could be improved. The study
      comprises 119 mesotheliomas of epithelial or mixed phenotype and 57
      adenocarcinoma metastases in the pleural cavity. The differences between the 2
      groups were highly significant for all recorded parameters, but typical
      reactivity for all parameters was seen in only 6 (5.0%) of the 119 mesotheliomas.
      An algorithm based on stepwise logistic regression was used to interpret
      divergent reaction patterns. Most diagnostic information was obtained with 8 of
      the parameters studied. The resulting algorithm identified almost 90% of the
      mesotheliomas with high specificity. The battery can be performed in 2 steps:
      several adenocarcinomas first are diagnosed with a few antibodies, applying the
      rest of the battery on the remaining unresolved cases.

PMID- 10941336
TI  - Cytology of angiosarcoma. Findings in fourteen fine-needle aspiration biopsy
      specimens and one pleural fluid specimen.
AB  - We report the cytologic features of 15 cases of angiosarcoma from various sites
      and include 14 fine-needle aspiration (FNA) biopsy specimens and 1 pleural fluid
      specimen. Six were initial diagnoses with histologic confirmation; an additional
      case in the liver was an initial diagnosis without tissue confirmation. One case
      represented lymph node metastasis from a primary prostatic epithelioid
      angiosarcoma. In 10 cases, immunohistochemical staining for factor VIII-related
      antigen, CD34, CD31, or Ulex europaeus agglutinin I was performed on the cytology
      or histology specimen. The aspirates varied in cellularity, and the degree of
      nuclear atypia ranged from relatively bland in a case of low-grade angiosarcoma
      of the prostate to highly pleomorphic in a lymph node metastasis from a facial
      cutaneous angiosarcoma. Vasoformative features such as intracellular RBCs, well
      formed vessels, attempts at microacinar/lumen formation, and intracytoplasmic
      lumens were variably present. The background was bloody in all specimens, with
      necrosis in rare cases. This cytologic series emphasizes that the cytologic
      features are heterogeneous but that the diagnosis can be suggested by fine-needle
      aspiration (FNA) when vasoformative features are present. The diagnosis can be
      made conclusively by FNA with immunocytochemical confirmation of endothelial
      differentiation.

PMID- 10941337
TI  - Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the
      lung in southern China.
AB  - Having reviewed the data on 3,663 consecutive cases of primary lung carcinoma in
      southern China, we found that 32 cases could meet the criteria for
      lymphoepithelioma-like carcinoma (LELC) of the lung. To study the relationship
      between pulmonary LELC and Epstein-Barr virus (EBV) infection, we used in situ
      hybridization and immunohistochemistry techniques to detect the EBV-encoded small
      nonpolyadenylated RNA (EBER), latent membrane protein 1 (LMP1), and viral capsid
      antigen (VCA) in 32 cases of LELC and 19 cases of non-LELC lung carcinoma. Of the
      32 cases, 30 (94%) showed EBER positivity. Of the 30 EBER-positive pulmonary LELC
      cases, 16 and 7 expressed LMP1 and VCA, respectively. In contrast with LELC, none
      of the 19 cases of non-LELC lung carcinoma showed EBER-, LMP1-, or VCA-positive
      signals in carcinoma cells. The results demonstrate that there is a close
      relationship between EBV infection and pulmonary LELC. EBV infection may have an
      essential role in the tumorigenesis of pulmonary LELC. EBV latent infection is
      the main status in pulmonary LELC except for individual EBV entering into a lytic
      cycle.

PMID- 10941338
TI  - Immunohistochemical and in situ hybridization studies of influenza A virus
      infection in human lungs.
AB  - Influenza viruses are responsible for acute febrile respiratory disease. When
      deaths occur, definitive diagnosis requires viral isolation because no
      characteristic viral inclusions are seen. We examined the distribution of
      influenza A virus in tissues from 8 patients with fatal infection using 2
      immunohistochemical assays (monoclonal antibodies to nucleoprotein [NP] and
      hemagglutinin [HA]) and 2 in situ hybridization (ISH) assays (digoxigenin-labeled
      probes that hybridized to HA and NP genes). Five patients had prominent
      bronchitis; by immunohistochemical assay, influenza A staining was present
      focally in the epithelium of larger bronchi (intact and detached necrotic cells)
      and in rare interstitial cells. The anti-NP antibody stained primarily cell
      nuclei, and the anti-HA antibody stained mainly the cytoplasm. In 4 of these
      cases, nucleic acids (ISH) were identified in the same areas. Three patients had
      lymphohistiocytic alveolitis and showed no immunohistochemical or ISH staining.
      Both techniques were useful for detection of influenza virus antigens and nucleic
      acids in formalin-fixed paraffin-embedded tissues and can enable further
      understanding of fatal influenza A virus infections in humans.

PMID- 10941339
TI  - Peripheral T-cell lymphoma complicated by a proliferation of large B cells.
AB  - We studied 14 cases that showed a morphologic appearance of peripheral T-cell
      lymphoma and contained substantial numbers of CD20+ large B cells. In all but 2
      cases, the CD20+ large cells showed a mix of kappa and lambda light chain
      expression. Two cases showed a focal predominance of kappa expression. In situ
      hybridization using the EBER1 probe for detection of Epstein-Barr virus (EBV) RNA
      was performed on every case. EBV RNA was present in 10 cases. Of 8 cases with EBV
      RNA stained by immunohistochemistry for the latent membrane protein of EBV, 6
      were positive. Double-labeling immunohistochemistry and in situ hybridization
      confirmed that EBV was present in the large B cells. Polymerase chain reaction
      (PCR) analysis showed a clonal rearrangement of the T-cell receptor (TCR)-gamma
      chain gene in 12 of 13 cases tested. One additional case showed a clonal
      rearrangement of the TCR-beta chain gene by Southern blot hybridization. PCR
      analysis showed a clonal immunoglobulin gene rearrangement in 5 cases, a
      suggestion of a clonal rearrangement in 1, an oligoclonal pattern in 4, and a
      polyclonal pattern in 4. The finding of large B and T cells may result in a
      misdiagnosis of a reactive process or of T-cell-rich B-cell lymphoma. The
      presence of EBV in some cases could cause further confusion with the reactive T-
      and B-immunoblastic proliferation of infectious mononucleosis.

PMID- 10941340
TI  - Detection of chromosome 11q13 breakpoints by interphase fluorescence in situ
      hybridization. A useful ancillary method for the diagnosis of mantle cell
      lymphoma.
AB  - We assessed cytologic specimens from 11 mantle cell lymphomas (MCLs) and 32 other
      B-cell non-Hodgkin lymphomas (NHLs) for 11q13 breakpoints using a 2-color
      fluorescence in situ hybridization (FISH) assay that uses an 11q13 probe centered
      on the CCND1 gene and a centromeric chromosome 11 probe (CEP11). The number of
      nuclei in 200 cells were counted, and results were expressed as an 11q13/CEP11
      ratio. All MCLs showed a high percentage of interphase nuclei with 3 or more
      11q13 signals (mean, 74.8%; range 57%-90%). In contrast, in other B-cell NHLs the
      mean percentage of cells with 3 or more 11q13 signals was 9.2%. All MCLs had an
      elevated 11q13/CEP11 ratio (mean, 1.38). The mean ratio for other B-cell NHLs was
      0.99. Two non-MCL cases, 1 large B-cell and 1 B-cell unclassified NHL, had high
      11q13/CEP11 ratios of 1.15 and 1.30, respectively. Conventional cytogenetic
      analysis performed on the former case revealed a t(5;11)(q31;q13). Interphase
      FISH analysis using 11q13 and CEP11 probes is a convenient ancillary method for
      assisting in the diagnosis of MCL. This commercially available assay is simple to
      use on cytology or imprint specimens, and results can be obtained within 24
      hours.

PMID- 10941341
TI  - Follicular lymphoma can be distinguished from benign follicular hyperplasia by
      flow cytometry using simultaneous staining of cytoplasmic bcl-2 and cell surface
      CD20.
AB  - The distinction between benign follicular hyperplasia (FH) and follicular
      lymphoma (FL) is sometimes problematic. We wanted to determine whether the
      expression of bcl-2 of FH was quantitatively different from that of FL, using
      surface CD20 expression as a discriminator of the various lymphoid compartments.
      Lymph node cell suspensions from 12 cases of FH and 17 cases of FL were analyzed
      by flow cytometry using a combined surface CD20 and intracellular bcl-2 staining.
      CD20- T cells in FH demonstrated the same bcl-2 expression as the CD20+ mantle
      cells, but the bright CD20+ germinal center cells showed near absence of bcl-2
      expression. In contrast, the neoplastic cells of FL showed greater bcl-2
      expression than the T cells of the same tumors and all cell populations of FH.
      This difference was particularly significant between the neoplastic B cells of FL
      and the germinal center cells of FH. The combined analysis of CD20 and bcl-2
      should be useful for the differential diagnosis between FH and FL and
      particularly applicable to limited samples or when B-cell clonality is in
      question. Whether the quantitation of bcl-2 expression can be of further
      discriminatory value in malignant lymphomas remains to be determined.

PMID- 10941342
TI  - Large B-cell lymphoma of thyroid. Two cases with a marginal zone distribution of
      the neoplastic cells.
AB  - We report 2 cases of B-cell lymphoma of the thyroid in which although a marginal
      zone distribution of the neoplastic cells was present, the cytologic features of
      the cells indicated large cell lymphoma. One of the cases showed an accumulation
      of crystalline inclusions within the cytoplasm of the neoplastic cells. Many of
      these inclusion-bearing cells showed plasmacytoid features. By
      immunohistochemical studies performed on formalin-fixed paraffin-embedded tissue,
      both of the cases showed a B-cell phenotype as indicated by CD20 expression, and
      1 showed kappa light chain restriction. In both cases, Ki-67 staining
      corroborated the impression of an aggressive neoplasm with staining of 50% and
      90% of the tumor cells. Both patients received cyclophosphamide, doxorubicin,
      vincristine, and prednisone with radiation therapy, and both are without evidence
      of disease after 17 and 18 months of follow-up. It is important to recognize this
      pattern of large B-cell lymphoma of the thyroid gland. While the indolent course
      typical of most low-grade extranodal marginal zone lymphomas is not likely in
      these cases, the outcome may be favorable if patients are treated aggressively
      with therapy for large cell lymphoma.

PMID- 10941343
TI  - Association of the prothrombin G20210A mutation with factor V Leiden in a
      midwestern American population.
AB  - The prothrombin G20210A mutation has been identified as a risk factor for
      thrombosis. We studied the relationship between prothrombin G20210A and factor V
      Leiden mutations in patients with thrombophilia. The first 264 patients for whom
      these molecular diagnostic studies were requested at our institution were
      included in the study. For 116 of the 264 patients, additional coagulation test
      results were available in the laboratory database. The prothrombin G20210A
      mutation was found in 16 (6.1%) of the patients and the factor V Leiden mutation
      in 44 (16.7%). Of the 16 patients with the prothrombin G20210A mutation, 8 also
      carried factor V Leiden; this association was significant. In contrast, only 2
      patients of the 116 with additional coagulation testing harbored more than 1
      prothrombotic risk factor. These data support the hypothesis that thrombophilia
      is a multigenic disorder. Among unselected samples from a Midwestern population
      evaluated for thrombotic risk factors, the prevalence of factor V Leiden and
      prothrombin G20210A mutations are similar to those found in other populations in
      the Western world.

PMID- 10941344
TI  - A survey of aPTT reporting in Canadian medical laboratories. The need for
      increased standardization. Thrombosis Interest Group of Canada.
AB  - A survey of all licensed medical laboratories performing activated partial
      thromboplastin time (aPTT) testing in Canada was undertaken; the response rate
      was 50.7%. Preanalytic phase of testing seemed generally satisfactory, although
      46% of laboratories were still using 3.8% or a 129-mmol/L concentration of
      citrate, and only 59% of institutions routinely performed testing to verify the
      platelet-poor status of the plasma used for aPTT testing. There were also
      concerns relating to the speed and duration of centrifugation for specimen
      preparation. While more than 67% of institutions had established an individual
      therapeutic range for aPTT testing, only 47% of laboratories verified this range
      with heparinized samples. Approximately 67% of the institutions that had verified
      the range had done this by spiking heparin concentrations into pooled plasma
      rather than using ex vivo specimens from patients receiving heparin therapy.
      There seemed to be a need for increased education about circumstances under which
      the therapeutic range should be rechecked and current standards for screening for
      the lupus anticoagulant. More than 71% of Canadian institutions surveyed used low
      molecular-weight heparin, which may obviate many of the issues surrounding aPTT
      testing. Overall performance as documented by survey results seemed similar to
      that reported for the United States and Australasia.

PMID- 10941345
TI  - Improved platelet counting using two-dimensional laser light scatter.
AB  - Clinical management of platelet disorders depends on accurate platelet counts. We
      evaluated a new analytic approach for platelet counting based on improved
      platelet discrimination. Current automated counting methods provide accurate
      platelet counts for most samples but often are unable to discriminate platelets
      accurately from nonplatelet particles such as microcytic RBCs, RBC fragments, and
      cellular debris that may falsely elevate platelet counts. The new approach
      measures 2 light-scatter angles of platelets and nonplatelet particles as they
      pass through a laser beam. The volume and refractive index of each platelet and
      particle are derived from the light-scatter measurements using the Mie scattering
      theory. Together, these 2 measurements provide improved platelet discrimination
      compared with 1-dimensional methods. With its improved discrimination, 2
      dimensional platelet analysis provides more accurate platelet counts in samples
      containing interfering particles and may contribute to more effective clinical
      management of patients with platelet disorders.

PMID- 10941346
TI  - Too optimistic?

PMID- 10941347
TI  - Benign transport of breast epithelium?

PMID- 10941348
TI  - Another variable in lymph node biopsy.

PMID- 10941349
TI  - Serotonin syndrome. Presentation of 2 cases and review of the literature.
AB  - Serotonin syndrome is an underreported complication of pharmacotherapy that has
      been relatively ignored in the medical literature. We discuss 2 recent cases seen
      at our institution and 39 cases described in the English-language literature
      since 1995. We found that patients with serotonin syndrome most often (74.3%)
      presented within 24 hours of medication initiation, overdose, or change in
      dosage. The most common presenting symptoms and signs were confusion, agitation,
      diaphoresis, tachycardia, myoclonus, and hyperreflexia. The prevalences of
      hypertension, coma/unresponsiveness, seizures, and death were not as prominent in
      our study as previously reported, perhaps reflecting earlier recognition and
      intervention. The most common therapeutic intervention was supportive care alone
      (48% of patients). The use of 5-hydroxytryptamine (5-HT) antagonists such as
      cyproheptadine, however, has become more common and might reduce the duration of
      symptoms. Only 1 death occurred, and most patients (57.5%) had complete
      resolution of their symptoms within 24 hours of presentation. The increased use
      of serotonergic agents (alone and in combination) across multiple medical
      disciplines presents the possibility that the prevalence and clinical
      significance of this condition will rise in the future. Internists will need to
      be increasingly aware of and prepared for this pharmacologic complication.
      Prevention, early recognition of the clinical presentation, identification and
      removal of the offending agents, supportive care, and specific pharmacologic
      therapy are all important to the successful management of serotonin syndrome.

PMID- 10941350
TI  - Bacteremic and nonbacteremic pneumococcal pneumonia. A prospective study.
AB  - We prospectively identified cases of pneumococcal pneumonia and used stringent
      criteria to stratify them into bacteremic and nonbacteremic cases. Although
      patients were distributed among racial groups in proportion to all patients seen
      at this medical center, the proportion of African-Americans with bacteremic
      disease was significantly increased. All patients had at least 1 underlying
      condition predisposing to pneumococcal infection, and most had several. Although
      the mean number of predisposing factors was greater among bacteremic patients
      than nonbacteremic patients, only alcohol ingestion was significantly more
      common. Nearly one-third of patients had substantial anemia (hemoglobin < or = 10
      g/dL) on admission, which may have predisposed to infection. In the case of other
      laboratory abnormalities, such as albumin, creatinine, and bilirubin, it was
      difficult to determine which abnormality might have predisposed to pneumococcal
      infection and which might have resulted from it. The radiologic appearance was
      varied. Airspace consolidation and air bronchogram on chest X-ray were highly
      associated with bacteremic disease, as was the presence of pleural effusion.
      Although the Pneumonia Patient Outcomes Research Team (PORT) risk score was a
      predictor of mortality, it did not help to predict the presence of bacteremia in
      an individual case. Most patients who died in the first week in hospital were
      bacteremic, and a high PORT risk score with bacteremia reliably predicted a high
      likelihood of a fatal outcome. Eleven patients had extrapulmonary disease with
      meningitis, empyema, and septic arthritis predominating; all of these patients
      were bacteremic. The antibiotic susceptibility of our strains correlated well
      with those that have been reported in the United States during the years of this
      study. The use of numerous antibiotics of different classes in many patients,
      especially those who were the most ill, precluded analysis of outcome based on
      antibiotic therapy. Only 17 patients had been vaccinated. Since nearly all
      patients had conditions for which pneumococcal vaccine is recommended and more
      than one-third had been hospitalized in the preceding 6 months, the low rate of
      vaccination can be regarded as a missed opportunity to administer a potentially
      beneficial vaccine.

PMID- 10941351
TI  - Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review
      of the literature. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines"
      Pulmonaires (GERM"O"P).
AB  - Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis primarily
      associated with necrotizing glomerulonephritis and pulmonary capillaritis. In
      this retrospective study of 29 patients with MPA and alveolar hemorrhage (AH), we
      characterized the pulmonary manifestations at presentation and assessed the short
      and long-term outcome. AH was diagnosed when bronchoalveolar lavage was
      macroscopically bloody, or contained hemosiderin-laden macrophages, in the
      absence of lung infection or pulmonary edema. MPA was diagnosed when AH was
      associated with focal segmental necrotizing glomerulonephritis at kidney biopsy
      or pathologically proved small-vessel vasculitis. There were 17 women and 12 men,
      with a mean age of 55.8 +/- 16.7 years. The onset was rapidly progressive, but in
      8 (28%) patients, symptoms preceded the diagnosis for more than 1 year. The most
      constant systemic findings associated with AH were glomerulonephritis in 28 (97%)
      patients; fever (62%); myalgia and arthralgia (52%); weight loss (45%); ear,
      nose, and throat symptoms (31%); and skin involvement (17%). Lung opacities were
      bilateral in 26 (90%) patients, most frequently involving the lower part of the
      lungs. Bronchoalveolar lavage, performed in 27 patients, was hemorrhagic in 25
      (93%), and contained numerous siderophages in others. Most patients were severely
      anemic (mean hemoglobin, 8.1 +/- 1.8 g/dL). ANCA, present in 27 (93%) patients,
      gave a perinuclear (14), cytoplasmic (11), or mixed (1) pattern. Mean serum
      creatinine level was 407 +/- 415 mumol/L. Renal biopsy confirmed the presence of
      necrotizing glomerulonephritis in 27 patients. Patients were treated with
      corticosteroids (100%), cyclophosphamide (79%), plasmapheresis (24%), dialysis
      (28%), and mechanical ventilation (10%). The overall mortality rate was 31% (9
      patients). Deaths were related to vasculitis (5 patients) or side effects of
      treatment (4). Deaths were more frequent in aged or mechanically ventilated
      patients. The 5-year survival rate was 68%. The recovery of respiratory function
      among survivors was clinically considered complete in 20 (69%) patients. However,
      7 patients (24%) had persistent alterations on pulmonary function tests. Of the
      11 patients who had relapses, 2 died from AH.

PMID- 10941352
TI  - Medical hazards of the tear gas CS. A case of persistent, multisystem,
      hypersensitivity reaction and review of the literature.
AB  - A 30-year-old incarcerated man was sprayed with the "tear gas" ortho
      chlorobenzylidene malononitrile (CS). He was hospitalized 8 days later with
      erythroderma, wheezing, pneumonitis with hypoxemia, hepatitis with jaundice, and
      hypereosinophilia. During the subsequent months he continued to suffer from
      generalized dermatitis, recurrent cough and wheezing consistent with reactive
      airways dysfunction syndrome, and eosinophilia. These abnormalities responded to
      brief courses of systemic corticosteroid but recurred off therapy. The dermatitis
      resolved gradually over 6-7 months, but the patient still had asthma-like
      symptoms a year following exposure. Patch testing confirmed sensitization to CS.
      The mechanism of the patient's prolonged reaction is unknown but may involve cell
      mediated hypersensitivity, perhaps to adducts of CS (or a metabolite) and tissue
      proteins. This is the first documented case in which CS apparently caused a
      severe, multisystem illness by hypersensitivity rather than direct tissue
      toxicity. Both the ethics and safety of CS use remain controversial, in part
      because of the difficulty documenting sporadic injuries received in the field,
      and also because the charged circumstances surrounding CS use may lead to both
      underreporting and exaggerated claims of medical harm. The medical literature on
      CS focuses mainly on its immediate irritant effects and on transient dermal and
      ocular injuries, with only 2 prior case reports of acute lung injury related to
      CS exposure. Given the paucity of documented lasting effects despite its
      widespread use for more than 3 decades, CS appears to be safe when deployed
      (outdoors) in a controlled manner, but it can cause important injuries if misused
      or if applied to a sensitized individual.

PMID- 10941353
TI  - Clinically significant and biopsy-documented renal involvement in primary Sjogren
      syndrome.
AB  - Clinically significant renal involvement in patients with primary Sjogren
      syndrome (pSS) has been described previously only in isolated case reports. The
      prevalence and significance of the 2 described syndromes, interstitial nephritis
      (IN) and glomerulonephritis (GMN), are not well known. In a cohort of 471
      patients with pSS who were followed for a mean of 10 years, 20 patients (4.2%)
      developed overt renal disease. Eighteen patients underwent a percutaneous renal
      biopsy; 2 patients declined. Ten patients had IN, 8 patients had GMN, and 2
      patients presented with both entities. Glomerular histology disclosed changes
      compatible with membranoproliferative GMN in 5 patients and mesangial
      proliferative GMN in 4 patients. Patients with IN had a younger disease onset
      compared with patients with GMN (mean, 36.8 compared with 46.0 yr, p 5 0.063).
      Patients with GMN had longer disease duration compared with patients with IN
      (mean, 2.2 compared with 8.0 yr, p 5 0.001). The majority of patients with GMN
      (80%) had mixed monoclonal cryoglobulinemia IgMk (type II) and lower complement
      C4 levels. Two patients (both with GMN) developed chronic renal failure requiring
      hemodialysis. Overall, clinically significant renal involvement is infrequent in
      pSS. IN occurs early in the disease process, while GMN is a late sequela and may
      have a less favorable prognosis.

PMID- 10941354
TI  - Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3
      Aspergillus Study Group.
AB  - A review of representative cases of invasive aspergillosis was conducted to
      describe current treatment practices and outcomes. Eighty-nine physicians
      experienced with aspergillosis completed case forms on 595 patients with proven
      or probable invasive aspergillosis diagnosed using modifications of the Mycoses
      Study Group criteria. Pulmonary disease was present in 56%, with disseminated
      infection in 19%. The major risk factors for aspergillosis were bone marrow
      transplantation (32%) and hematologic malignancy (29%), but patients had a
      variety of underlying conditions including solid organ transplants (9%), AIDS
      (8%), and pulmonary diseases (9%). Overall, high antifungal failure rates
      occurred (36%), and complete antifungal responses were noted in only 27%.
      Treatment practices revealed that amphotericin B alone (187 patients) was used in
      most severely immunosuppressed patients while itraconazole alone (58 patients) or
      sequential amphotericin B followed by itraconazole (93 patients) was used in
      patients who were less immunosuppressed than patients receiving amphotericin B
      alone. Response rate for patients receiving amphotericin B alone was poor, with
      complete responses noted in only 25% and death due to or with aspergillosis in
      65%. In contrast, patients receiving itraconazole alone or following amphotericin
      B had death due to or with Aspergillus in 26% and 36%, respectively. These
      results confirm that mortality from invasive aspergillosis in severely
      immunosuppressed patients remains high even with standard amphotericin B.
      Improved responses were seen in the less immunosuppressed patients receiving
      sequential amphotericin B followed by itraconazole and those receiving
      itraconazole alone. New approaches and new therapies are needed to improve the
      outcome of invasive aspergillosis in high-risk patients.

PMID- 10941355
TI  - Aspergillus valve endocarditis in patients without prior cardiac surgery.
AB  - Aspergillus native valve endocarditis in patients who have not had cardiac
      surgery is uncommon. We report 3 cases and review 58 other adult patients
      reported in the English-language literature. Sixty-seven percent of the patients
      had underlying immunosuppression. The clinical features were fever (74%), embolic
      episodes (69%), a new or changing heart murmur (41%), and sudden visual loss
      (13%). Patients with mural endocarditis were more often immunosuppressed,
      especially due to solid organ transplants, but had lower frequency of heart
      murmurs and embolic episodes. Echocardiography revealed a vegetation in 78% of
      all the cases in which it was performed. Examination and culture of biopsy
      material often helped to establish a diagnosis of Aspergillus infection. Twenty
      five patients had an antemortem diagnosis. These patients received a mean
      cumulative amphotericin B dose of 27 mg/kg. Twenty percent (3/15) of patients who
      received combined surgical and medical therapy survived, compared to none of
      those who received medical therapy alone (p = 0.08). Patients who survived were
      not immunosuppressed. We conclude that native valve aspergillus infective
      endocarditis is uniformly fatal without surgical intervention and antifungal
      therapy.

PMID- 10941356
TI  - Central nervous system aspergillosis in patients with human immunodeficiency
      virus infection. Report of 6 cases and review.
AB  - Central nervous system (CNS) aspergillosis is a relatively uncommon complication
      of human immunodeficiency virus (HIV) infection. We describe 6 patients with the
      acquired immunodeficiency syndrome (AIDS) who developed CNS aspergillosis, and we
      review a total of 33 cases of CNS aspergillosis among HIV-infected individuals
      that were diagnosed by histology and/or culture. All patients were diagnosed with
      advanced HIV infection. Major risk factors for the disease included neutropenia
      and corticosteroid use. The most common presenting symptoms were nonspecific
      neurologic manifestations including headache, cranial or somatic nerve weakness
      or paresthesia, altered mental status, and seizures. The most common sites of
      additional Aspergillus involvement were the lungs, sinuses, ears, and orbits,
      while in one-fourth of the cases CNS was the only site of Aspergillus infection.
      The final diagnosis of CNS aspergillosis was made on autopsy in more than half
      the cases, and medical treatment of CNS aspergillosis was unsuccessful in all
      cases. CNS aspergillosis should be included in the differential diagnosis of HIV
      infected patients who present with nonspecific neurologic symptoms and signs. If
      we take into account the much higher prevalence of invasive aspergillosis of the
      lungs, the findings in the present report suggest that CNS aspergillosis in HIV
      infected individuals occurs more often as a result of direct extension from the
      sinuses, orbits, and ears than through hematogenous spread from the lungs.
      Physicians should be aware that the CNS might be the only site of Aspergillus
      involvement and include CNS aspergillosis in the differential diagnosis of HIV
      infected patients presenting with focal neurologic signs and symptoms, especially
      when the head CT reveals hypodense lesions.

PMID- 10941357
TI  - Aspergillosis update.

PMID- 10941358
TI  - [Radiology in Russia--chief landmarks (75th anniversary of the Russian scientific
      center of radiology of the RF Health Ministry)].

PMID- 10941359
TI  - [Problems of radiologic diagnosis in oncology].

PMID- 10941362
TI  - [Computerized tomography of solitary lung metastasis].
AB  - Experience has pointed to a rather low potential of traditional procedures of
      roentgenography and tomography in detecting small foci (ca. 4-5 cm in dia.).
      Metastases are often not seen in the shadow of the ribs, diaphragm and cardio
      vascular complex. X-ray computed tomography (CT) is a method of choice for early
      diagnosis and further tracking tumor process in the lung. Superior spatial
      resolution offers complete summation-free visualization of the lung parenchyma.
      Provision of more data, including information on "occult" pathology in the lung,
      is instrumental in confirming or rejecting diagnosis of solitary tumor.

PMID- 10941361
TI  - [Long-term results of interstitial gamma-therapy for cancer of the mucosa of
      tongue and oral cavity fundus].
AB  - The methodology and end results of interstitial radiotherapy and combined and
      complex limb-preserving treatment for carcinoma of the mucosa of the tongue and
      fundus of the oral cavity have been studied. 60Co ionizing radiation pin-sources
      with high-level activity at tips were employed.

PMID- 10941360
TI  - [Diagnosis of prostate cancer].

PMID- 10941363
TI  - [Results of combined treatment of patients with rectal cancer using a single
      preoperative radiotherapy dose of 7.5 Gy].
AB  - The results of 3-year combined and surgical treatment of 173 patients with rectal
      tumors are discussed. Single dose of 7.5 Gy was administered to 83 patients on
      the eve of radical surgery. Ninety patients in control received radical surgery
      alone. One-, two- and three-year radical cure rates in the study group were
      higher by 22.9, 21.2 and 29.3%, respectively, while 3-year recurrence-free
      survival in the same group was 2.7 times that in the surgical patients.

PMID- 10941364
TI  - [Single preoperative radiation exposure for stage II breast cancer].
AB  - The efficacy of different combinations of radiotherapy and mastectomy after
      Madden was compared in 411 patients with stage II breast tumors. The least
      likelihood of local reccurence (4.5 +/- 1.3%) was recorded after single exposure
      before mastectomy and with/without adjuvant irradiation of the regional
      lymphatics (group I); it appeared 1.5 times as high (7.0 +/- 2.1%) after
      mastectomy + postoperative irradiation (group II) while the highest frequency
      (14.8 +/- 5.4%) was registered after surgery alone (group III). Relapse-free 10
      year survival was observed in 63.5 +/- 4.7 (group I), 77.4 +/- 4.6 (group II) and
      46.2 +/- % (group III), respectively, the difference between group I and II being
      significant. Therefore, postoperative radiotherapy in conjunction with mastectomy
      (Madden) should be recommended for stage II breast carcinoma when the breast
      cannot be salvaged.

PMID- 10941365
TI  - [Monitoring the changes of the lesion and of the patient's health condition in
      the course of radiotherapy].
AB  - The effect of therapy of malignancies is at present monitored by X-ray procedures
      on the basis of the dynamics of the size of lesion. Since such approach fails to
      provide data on the structure of lesion changes and response to treatment, it is
      suggested that structural changes in cells of exposed tissues can by monitored by
      using densitometric data obtained from mammograms and (computed) tomograms, to
      assess density changes in tumor and adjacent normal tissues. Recovery involves
      certain systemic changes which can be identified using certain peripheral blood
      indices; the latter are evaluated using non-statistical applications of the
      theory of pattern recognition and cluster analysis.

PMID- 10941366
TI  - [Results of peripheral densitometry in a population of postmenopausal women].
AB  - Osteodensity was compared in 582 postmenopausal patients with such pathologies as
      urogenital atrophy, osteoporosis, vulvar craurosis, breast carcinoma, hyperplasia
      and endometrial carcinoma. A double-photon Z-ray densitometer with a computer
      program designed for postmenopausal women examination was employed. It was shown
      that osteodensity measurements can distinguish two opposite patterns of
      homeostasis in postmenopause: involute-atrophic vs. hyperplastic processes in
      target tissues characterized by high oncological susceptibility. However, if
      strict and clear distinctions are applied, many patterns of pathology combination
      so typical of postmenopause will stay outside the classification. Much in further
      studies of the problem will depend on progress made in investigation of estrogen
      receptors in target tissues.

PMID- 10941367
TI  - [New trends in the radiodiagnosis of extensive malignancies of the maxilla and
      nasal cavity and paranasal sinus mucosa].
AB  - Application of computed (CT) and magnetic resonance tomography (MRT) provided
      means of precise sitting of tumor and identifying boundaries of adjacent tissue
      involvement. The study established certain characteristics of CT detection of
      bone damage. It also showed MRT superiority in visualizing the soft-tissue
      component of neoplasm and distinguishing between tumor tissue and concomitant
      secondary inflammation.

PMID- 10941368
TI  - [Current diagnosis and combined and radiation therapy of pancreato-biliary cancer
      in patients with jaundice].
AB  - The effectiveness of therapy of pancreato-biliary cancer in jaundice patients has
      been raised due to introduction of sparing slightly-invasive (percutaneous,
      transhepatic) procedures for suppression of choleostasis and restoring biliary
      return to intestine. Also, such measures as pancreato-digestive anastomosis,
      radical surgery to compensate jaundice-related functional and morphological
      disorders and changes in the liver as well as perfection of procedures of
      combined and radiation therapy were used.

PMID- 10941370
TI  - [Radiotherapy for cystadenoma of the trachea].
AB  - Radiation as a method of treatment was carried out in 16 (25.0%) out of 64
      patients with tracheal adenocystoma (radical dosage of 50-70 Gy (12) and
      palliative--40-48 Gy (4). The dosimetric profile consisted of the cervical,
      cervico-thoracic, thoracic and bifurcation sections of the trachea. Complete
      resorption of tumor was registered in 12, partial--3, no effect in 1 cases. Three
      , five- and ten-year survival was 65.2 +/- 12.6; 55.9 +/- 13.5 and 10.4 +/-
      13.1%, respectively.

PMID- 10941369
TI  - [Treatment for squamous cell carcinoma of the trachea].
AB  - Treatment of squamous-cell tracheal tumors was given to 85 patients. Surgery was
      carried out in 48 (56.5%), radical resection--22 (25.9%). Distant metastases
      detected preoperatively in 19 (22.4%) patients were an absolute contraindication
      for radical surgery. Combined therapy was received by 14 cases without any grave
      postoperative complications. Three- and five-year survival after combined and
      surgical treatment was 59.9 +/- 10.5 and 40.9 +/- 10.5%, respectively. Radiation
      was given to 48 (56.5%) patients. This group included 26 cases of palliative
      operations and exploratory laparatomy. Three- and five-year survival after
      radiation was 30.1 +/- 6.7 and 27.6 +/- 6.7%, respectively.

PMID- 10941371
TI  - [Lung cancer: 30-year experience of surgical and combined treatment].
AB  - 6,212 lung cancer patients have been examined and treated. The data on surgical
      and combined treatment of 2,702 patients have been analyzed. Postoperative
      complication incidence has dropped to 5.4% in recent years. End results have
      improved due to use of organ-saving, reconstructive and plastic procedures for
      the bronchi and trachea in conjunction with radiotherapy.

PMID- 10941372
TI  - [Surgical, radiation and combined treatment of multiple primary malignancies of
      the respiratory system].
AB  - Surgery for primary multiple malignant tumors of the respiratory system was
      carried out in 141 patients. Reconstruction, plastic operations and sparing
      resections were performed in 79 cases (68.5%). Five-year survival after radical
      surgery was 43.8%.

PMID- 10941373
TI  - [Invasive methods in complex radiologic diagnosis of breast diseases].
AB  - The report deals with such present-day invasive procedures of breast examination
      as X-ray-controlled puncture, puncture using X-ray contrast, Cytoguide video
      accessory unit controlled puncture biopsy, "pistol-needle" application,
      ultrasound aiming puncture, pneumocystography, ductography and preoperative
      interstitial marking of nonpalpable masses. If latest invasive procedures are
      used during complex examination of the breast, diagnostic accuracy can be raised
      to 95-97%.

PMID- 10941375
TI  - [Various aspects of individualized planning of computerized radiotherapy for
      uterine and ovarian cancer].
AB  - The study was concerned with radiotherapy planning using individual data on
      tissue volume to be treated. The investigation used criteria based on
      correlations of TDF, actual volume identified by ultrasound, computed and
      magnetic resonance tomography and dose fractionation regime. As a result, grave
      complication rates dropped 3 times including cases of locally advanced tumors,
      non-traditional dose fractionation and advanced regimens of polychemotherapy.

PMID- 10941374
TI  - [Current potential of sonography for primary and specific diagnosis of
      endometrial cancer].
AB  - Findings on sonography diagnostic potential to be used in screening for
      endometrial carcinoma suggested an ultrasound examination of 235 postmenopausal
      patients who had had no relevant complaints. As a result, criteria of ultrasound
      screening for endometrial tumors in postmenopausal patients were worked out.
      Later, sonography was carried out in 596 endometrial carcinoma patients with a
      view to verify the diagnosis. It pointed to inadequate identification of
      microinvasive carcinoma (up to 5 mm) by transabdominal and transvaginal scanning.
      Sonography, however, efficiently diagnosed marked infiltration (9.4%), organ
      involvement (88.4%) and metastatic lesions in the ovaries.

PMID- 10941376
TI  - [Radiotherapy of cerebellar medulloblastoma in children].
AB  - Out of 108 children with brain tumors, aged 3-15, receiving radiotherapy in 191
      1997, cerebral medulloblastoma was identified in 37 (34%). After total or
      subtotal excision of tumor, the latter were given 4-12 cycles of
      polychemotherapy. The brain and spinal marrow was exposed to 30-35 Gy followed by
      aiming 50-55 Gy irradiation of posterior cranial fossa. Three patients received
      radiation for recurrent tumor. One patient suffered demyelination as complication
      after repeated exposure. Out of 32 follow-up patients, 19 have survived an
      average of 33 months while 13 died having survived an average of 21 months. The
      main causes of failed therapy proved local progression of tumor and dissemination
      via liquor. Radical extent of surgery was used as the main prognostic factor.

PMID- 10941377
TI  - [Diagnostic significance of puncture biopsy for renal neoplasms].
AB  - 234 ultrasound-controlled punctures were performed for diagnostic purposes. Bulk
      renal material was sampled in 98.4% and neoplasia diagnosed by morphological
      analysis in 96.8%.

PMID- 10941378
TI  - [Value of prophylactic investigation of thoracic organs in victims of the
      Chernobyl power plant disaster].
AB  - Relatively low morbidity of tuberculosis of the lung (2 per 1,500) and
      comparatively high morbidity of ling cancer were reported in 1995-1997 among the
      liquidators of Chernobyl nuclear power station disaster. Risk of malignant
      disease involved in X-ray check-ups of the chest has been identified. Low
      diagnostic value of photoroentgenography for lung tumors has been reported.

PMID- 10941379
TI  - [Use of information technology in oncology practice at the Moscow Research
      Institute of Diagnosis and Surgery].
AB  - The report deals with introduction of such modern information technologies as
      electronic processing of documents and access to INTERNET data into diagnostic
      and therapeutic practice.

PMID- 10941380
TI  - Sprains of the radial collateral ligament of the metacarpophalangeal joint of the
      thumb. A series of 14 cases.
AB  - Fourteen surgically treated radial sprains of the M.P. joint of the thumb, are
      reported. 8 were recent cases, 6 were longstanding. At the time of surgery, the
      extensor head was severed in 4 cases, the APB tendon in 6 cases, the dorsal
      articular capsule in 9. The radial collateral ligament was elongated 6 times,
      ruptured 4 times, and presented bony avulsion in 4 cases. The mean postoperative
      immobilization was 37 days. 13 patients were reviewed with a mean follow-up of 22
      months. Only eight were satisfied. The mean loss of motion was 27 degrees. The
      mean laxity, assessed on specific dynamic X-rays, was 6 degrees. 3 patients
      presented with radiographic arthritis, all of them with chondral lesions at the
      time of surgery. Despite the absence of Stener's lesion, the authors recommend
      surgery when volar subluxation or radial laxity is observed > 10 degrees.

PMID- 10941381
TI  - Comparison of tendon suspension-interposition and silicon spacers in the
      treatment of degenerative osteoarthritis of the base of the thumb.
AB  - In a retrospective study, 75 patients with tendon suspension-interposition
      arthroplasty were compared with 27 patients with prosthetic replacement of the
      trapezium for CMC I osteoarthritis. A significant decrease in pain and an
      increase in subjective strength was observed in both groups. The extent of change
      was not significantly different between the two groups. Although there was
      radiographically less proximalisation of the thumb in the patient group with
      silastic interposition, objective strength and range of motion was not
      significantly different between the two groups. Since the results of
      trapeziectomy for the treatment of degenerative osteoarthritis of the base of
      thumb with or without silicone interposition are comparable, the use of silastic
      implants, with their inherent complications, no longer seems to be justified.
      There might be a place for the condylar type of implants in low-demand rheumatoid
      patients, in whom as much bone stock as possible should be preserved.

PMID- 10941382
TI  - [Metaphysis fracture of the distal radius: Kapandji's or Py's pinning?].
AB  - The authors report a prospective and randomized study comparing two pinning
      techniques for fractures of the distal radius. The series compared 42 patients
      treated by Kapandji's intrafocal pinning (Group I) and 46 patients treated by
      Py's isoelastic pinning (Group II). Secondary displacement was observed in 7
      patients in group I and in 2 patients in Group II. Secondary displacement of K
      wire was observed in 6 patients in group I and in no patient in group II.
      Functional results were analysed according to jakim's criteria. A significant
      difference was observed between the two groups, for global scores, objectives
      scores and radiological scores, with better results for Py's pinning. No
      significant difference was observed for subjective scores advantages of Py's
      pinning were: stability of isoelastic wires preventing posterior comminution and
      no need for radioscopic control. Kapandji's pinning is proposed in cases of lower
      and unstable fractures in teenagers without focal comminution and in T fractures.
      In the other cases of metaphyseal fractures with posterior displacement, Py's
      pinning could be proposed.

PMID- 10941383
TI  - [Sea urchin sting synovitis. Report of 4 cases].
AB  - Accidental sea urchin stings do not usually have any pathological consequences.
      However, cutaneous, synovial or toxic diseases can develop in some predisposed
      subjects, or under predisposing circumstances. The diagnosis, sometimes very
      delayed, can be difficult. Four personal cases of reactive arthritis or
      tenosynovitis, three of which affected the hand, are reported. All patients were
      cured after one or several surgical excisions. Antibiotics were not effective.
      The main clinical presentations, particularly delayed synovitis, are described.
      The various pathogenic hypotheses are in favour of an immunological reaction to
      the envelope protein of the sea urchin spikes.

PMID- 10941384
TI  - [MRI in the postoperative assessment of pseudoarthrosis of the scaphoid bone
      treated by corticocancellous bone graft. Report of 31 cases].
AB  - Thirty one scaphoid pseudarthroses treated by corticocancellous bone graft
      between November 1985 and December 1988 were reviewed with a mean follow-up of
      33.9 months. Clinical examination assessed pain, wrist mobility, and strength of
      grip. Radiological assessment evaluated consolidation of the corticocancellous
      graft, the presence or absence of graft resorption and the possible presence of
      radiocarpal osteoarthritis. A discordance between clinical and radiographic
      results was observed. Six patients had an excellent or good clinical result, but
      a poor radiological result and one patient with a poor clinical result presented
      an excellent radiological result. We therefore decided to use MRI to more clearly
      define the cause of this discordance and to verify the viability of the graft.

PMID- 10941385
TI  - Idiopathic tumoral calcinosis associated with congenital malformation of the
      hand. Case report.
AB  - The authors describe a case of tumoral calcinosis of the hand in a three-year-old
      child, involving the digits and carpus, and associated with ectrodactyly. The
      clinical features, diagnostic imaging procedures, particularly radiography and
      MRI, and therapeutic approach, in most cases radical excision, of this rare soft
      tissue tumour are discussed.

PMID- 10941386
TI  - Irreducible dorsal dislocation of the interphalangeal joint of the thumb due to
      the palmar plate. A case report.
AB  - Dorsal dislocation of the thumb interphalangeal joint is rare. Only very few
      cases of irreducible dislocation has been reported at this joint. The authors
      report a case of compound irreducible dislocation due to the palmar plate
      interposition. The sesamoid, the flexor pollicis longus have been reported to
      block reduction of the dorsal dislocation of the thumb interphalangeal joint
      doctors on casualities should not insist if reduction is not easily obtained, the
      patient should then be guide towards a surgical team for surgical treatment.

PMID- 10941387
TI  - [In vivo study of kinematics of the elbow using electromagnetic goniometer].
AB  - We used an electromagnetic goniometer to study the angular and translations
      displacements between the humerus and the 2 bones of the forearm. The
      electromagnetic gionometer allows acquisition of the coordinates and analysis of
      the 6 degrees of motion. To validate our external fixation apparatus, we used a
      fresh body upper limb. At first, a series of measurements was conducted with the
      apparatus. We then performed a series of measurements, by fixing the transmitter
      and receiver with external fixation pins directly inserted into the bones of the
      arm and forearm. To assess the reproducibility of our method, we chose a healthy
      subject. We performed 20 measurements over his right and left elbows. In order to
      study normal elbow kinematics, we performed measurements on 10 healthy subjects.
      The study of rotation showed that the apparatus was adapted to measure flexion
      extension. It limited pronation-supination movement to about 26.7 degrees.
      Abduction was increased by 19.7 degrees by our apparatus during flexion
      extension, but abduction was reliable within a 2 degrees range for pronation
      supination. The sliding movements recorded during flexion-extension were reliable
      within approximately 3 mm for frontal translations, 6 mm for fitting, and 1 mm
      for external translations. For the sliding movements recorded in pronation
      supination, frontal translations were reliable within about 7 mm, fitting was
      reliable within 1.9 mm and external translations were reliable within about 2.9
      mm. During flexion-extension of the elbow, flexion-extension, frontal
      translations and external translations were reproducible. The reproducibility
      test showed that only 6 measurements were reproducible. The kinematic elbow study
      of a healthy subject showed that the average amplitude of flexion-extension was
      close to the measurement observed with the manual goniometer. The results in the
      healthy subject showed that the elbow is more stable during pronation-supination
      than during flexion-extension. This preliminary study should allow us, in the
      near future, to study elbow prosthesis kinematics.

PMID- 10941388
TI  - [Technical improvement of the Kapandji-Sauve operation, called "Technique III"].
AB  - The tendon of the ECU in its sheath is the main element of stability of the ulnar
      stump. In the original procedure, it was necessary first to cut the ulna for
      downwards tilting of the ulnar head, so as to open the distal radio-ulnar joint
      to remove its cartilages. It is better to leave the ulnar head in place, just
      widening the dorsal aspect of the DRUJ and peel its cartilages. The ulnar head is
      then fixed with a cancellous screw in its place in the sigmoid notch. Just above
      this fixation, it is necessary to separate the ECU tendon included in its sheath
      from the ulnar shaft, only along a limited line 10-15 mm long, where the ulnar
      resection will be made. The ECU tendon is therefore not disconnected from the
      ulnar stump, which is better stabilized. In contrast with the original technique
      the ulnar resection is made in a second stage, with two ents: a distal and
      transverse ent, above the head fixation, and a proximal and oblique ent, making a
      tip on the medical side of the ulnar stump. Ulnar resection is consequently
      minimized by means of this obliquity. It is very important to check that this tip
      is 5 mm from the ulnar head cut in supination. The first eight cases show better
      stability of the stump and fast recovery of amplitudes of prono-supination. The
      patient feels "comfortable" after a period of two to six months. These advantages
      justify replacement of the previous technique by this procedure.

PMID- 10941389
TI  - [In Process Citation]

PMID- 10941390
TI  - Restoration of wrist extension by tendon transfer in cases of obstetrical
      brachial plexus palsy.
AB  - Sequelae from obstetrical brachial plexus palsy are sometimes severe even after
      early microsurgical repair. Tendon transfer may improve hand function but to
      date, there is no large series that has been published on the results. Fifty-six
      children with obstetrical brachial plexus palsies were operated on for lack of
      wrist extension. A functional assessment scale was developed. Postoperatively,
      42.5% of patients achieved an active wrist extension, 32.5% a static wrist
      extension. The extent of paralysis seems to influence the results. Some tendon
      transfert seems to give better results. The age at the time of transfert has no
      influence on the out come.

PMID- 10941391
TI  - Syndactyly in Apert syndrome. Utility of a prognostic classification.
AB  - The authors report a series of 36 patients of Apert's Syndrome in whom a genetic
      analysis was performed. 2 major types of mutation were found (S252W and P253R).
      The correlation between the type of mutation and certain clinical abnormalities
      allowed validation of Upton's modification of Blauth's classification and also
      helped add a prognostic indicator for the intellectual development of the child.
      Thus, global treatment of the child should take into account not just the
      clinical abnormalities but also its intellectual prospects.

PMID- 10941392
TI  - [Burn-induced contraction cicatrix in children. Review of 79 cases].
AB  - Post-burn flexion contractures of the hands are evaluated in this retrospective
      study concerning eighty-six hands of seventy-nine children in the pediatric
      surgery unit of the University hospital of Dakar from 1971 to 1995. A peak
      frequency was found among 2-months-old males. Fire (flames or embers) is the most
      frequent etiology (49.5%). The initial treatment of these burns is more often
      inadequate because it is performed in dispensaries (small clinics) or at home and
      then causes severe sequelae. Among the methods of treatment, excision with graft
      gives the best results in short flexion contractures. Isolated Z plasty can be
      used successfully. Our follow-up is short (6 months) but the results are
      relatively good. Among the factors influencing the results, the seriousness of
      the lesions, the type of surgical treatment, immobilization and physiotherapy are
      the most significant.

PMID- 10941393
TI  - Assessment of hand after brain damage with the aim of functional surgery.
AB  - The semiology of the hand after brain damage is really rich. Its clinical
      evaluation remains quite difficult and must be integrated in the neuro-orthopedic
      and cognitive context. Deficiency, neuropsychological, analytic and functional
      status, must be assessed before any surgical decision aiming the improvement of
      prehension. Neuropsychological evaluation precise the hemispheric specialization:
      right hemisphere lesions conduct to unilateral spatial neglect while left
      hemispherical lesions determine language troubles and gesture impairment
      (apraxia). The analytical evaluation describes motor and sensitive function and
      assesses spasticity and pain. Concerning the functional assessment, the
      Enjalbert's score seems to be the most adapted to the upper limb. The assessment
      of hand deficiency and its origin is necessary to orientate the surgical decision
      and includes the Zancolli classification for the fingers and wrist and the House
      classification for the thumb. These classification used for cerebral palsy seems
      to be insufficient for all the different situations occurring after brain damage.
      A new classification is proposed based on 3 parameters: fingers extension, thumb
      abduction and supination. Surgical decision should be examined only after an
      adapted rehabilitation program.

PMID- 10941394
TI  - Osteoligamentoplasty and limited dorsal capsulodesis for chronic scapholunate
      dissociation.
AB  - Treatment of chronic scapholunate dissociation remains unsatisfactory. As the
      dorsal part of scapholunate interosseous ligament (SLIL) seems to be the
      "critical corner" of the scapholunate stability, its replacement by an analogous
      structure could restore scapholunate stability. A procedure is described which
      combines reconstruction of the dorsal region of the SLIL by means of an
      osteoligamentous autograft, harvested at the carpus (dorsal trapezoidometacarpal
      II ligament) and limited dorsal capsulodesis. The limited dorsal capsulodesis is
      performed using the scaphotriquetral head of the dorsal intercarpal ligament left
      attached to the distal pole of the scaphoid and fixed with a bone anchor on the
      dorsal aspect of the lunate. The osteoligamentous autograft prevents scapholunate
      dissociation and dorsal scaphoid subluxation. The dorsal capsulodesis limits
      scaphoid flexion and allows synergistic scapholunate mobility. This combination
      should stabilize the scaphoid in the horizontal as well as sagittal planes. The
      advantages of this technique are: 1) a single incision; 2) replacement of a
      ligament by an analogous autograft; 3) faster healing by bone-to-bone apposition;
      4) more anatomic and physiologic reconstruction. Three patients are presented to
      illustrate the technique.

PMID- 10941395
TI  - The Herbert screw for delayed union and non-union of scaphoid fractures: a review
      of twenty-two cases.
AB  - We retrospectively reviewed 22 patients with delayed or non-union of scaphoid
      fractures treated with the Herbert screw. In 15 cases, we used an additional bone
      graft, taken from the iliac crest in all but two cases. The mean follow-up was 18
      months (range: 6-40 months). Twelve of the 14 non-unions and 7 of the 8 delayed
      unions healed. Eleven patients were pain-free, 7 had minor symptoms, one had
      major symptoms but still considered his situation to be improved and two did not
      obtain any clinical improvement.

PMID- 10941396
TI  - A trans STT, trans capitate perilunate dislocation of the carpus. A case report.
AB  - We report a case of carpal injury not previously described, associating three
      lesions of the carpus secondary to a hyperextension mechanism: fracture of the
      capitate, scapho-trapezio-trapezoid sprain and lunotriquetral ligament rupture.
      The patient was operated by percutaneous pinning after closed reduction. The
      capitate fracture was not fixed. At follow-up, the patient had no restriction of
      his everyday activities and was very satisfied.

PMID- 10941397
TI  - Analysis of two bone-prosthesis interfaces and membranes from non-cemented
      trapeziometacarpal prostheses.
AB  - The non-cemented Ledoux trapeziometacarpal prosthesis has a high failure rate. In
      order to better understand the mechanism responsible for pain and loosening, we
      thoroughly analysed the membranes surrounding the prosthesis and the bone
      prosthesis interface in two trapezia, each containing a Ledoux cup, which were
      resected after unsuccessful implantation. Serial sections, perpendicular to the
      longitudinal axis of the implanted cup, allowed histological examination of the
      interface and were used to quantify bone apposition. The tissues surrounding the
      prosthesis showed a foreign-body reaction to particles identified as titanium.
      The interface showed bony integration of the cup, mainly on the radial side and
      on the proximal part of the cup, with an appositional index of 28%. Our findings
      suggest that bony apposition might not be sufficient to ensure successful
      anchoring of the Ledoux cup in the trapezium in the presence of an intense
      foreign body reaction to titanium. Moreover, the presence of metal might be
      secondary to micromotion of the wings of the metallic part of the cup, induced by
      axial movement of the underlying polyethylene during pinch grip. The combination
      of polyethylene as an expander and titanium may need to be reviewed.

PMID- 10941398
TI  - Experimental median nerve repair by fresh or frozen nerve autografts and
      xenografts.
AB  - The authors described the reconstruction of a terminal branch of the brachial
      plexus (the median nerve) by different kinds of peripheral nerve grafts, in rats.
      Fresh or frozen autografts from Sprague-Dawley rats and fresh or frozen
      xenografts from Beagle dogs were used. Three, six, nine and twelve months after
      grafting, rats underwent histological assessment (muscle, nerve and spinal cord)
      and simple functional assessment by the grasping test. The immune reaction was
      prevented by the freezing and thawing method that had rendered xenografts
      acellular. This process allowed a satisfactory reinnervation of the flexor carpi
      radialis muscle (FCR) and a function recovery about 75% of control value.
      Nevertheless, the force recovery in rats that received frozen grafts was slower
      than those received fresh autografts. Probably, the destruction of cellular
      elements by freezing produced a deficient environment for nerve regeneration.
      However, this gap was partially compensated at twelve months after surgery by the
      maturation and the secondary adaptation of regenerated nerve fibers. Theses
      results showed that the force recovery is directly correlated to the capability
      of the nerve fibers to reproduce, histologically, a next to normal nerve pattern.

PMID- 10941399
TI  - Hormonal regulation of alternative splicing.

PMID- 10941400
TI  - Mechanism of tissue-specific alternative RNA processing of the calcitonin CGRP
      gene.

PMID- 10941401
TI  - RNA processing and the control of spermatogenesis.
AB  - The testis is a rich source for expression of mechanisms for gene regulation.
      Germ cell expansion and differentiation require many cellular changes and
      regulatory steps. In the developing germ cells, the length of mRNA transcripts
      often vary as the cells mature, reflecting the ongoing regulatory changes. Due to
      the numerous maturation stages that germ cells must undergo, novel gene
      regulation strategies have been developed that provide for flexible gene
      expression and protein function. Some of the methods employed in the testis to
      alter gene expression and function include the initiation of transcription at
      alternative start sites, the splicing in or out exons to alter the properties of
      the resulting protein, changes in the site of polyadenylation to control mRNA
      stability, and delays in the translation of transcripts to ensure a source of
      protein late in germ cell development after transcription ceases. Using these
      varied expression strategies, individual genes are able to perform different
      functions that can be directed to specific development timepoints.

PMID- 10941402
TI  - Connections between pre-mRNA processing and regulation of the eukaryotic cell
      cycle.

PMID- 10941403
TI  - Role of phosphorylation in pre-mRNA splicing.

PMID- 10941404
TI  - RNA editing.

PMID- 10941405
TI  - Polyadenylation and control of neuroendocrine gene expression.

PMID- 10941406
TI  - Reproductive and offspring developmental effects following maternal inhalation
      exposure to methanol in nonhuman primates.
AB  - INTRODUCTION: In an effort to improve air quality and decrease dependence on
      petroleum, the federal government, industry, and other groups have encouraged
      development of alternative fuels such as methanol to substitute for gasoline or
      diesel fuel. Methanol is also a candidate to provide the hydrogen for fuel cells,
      which are being developed for a variety of power sources (including motor vehicle
      engines). Before people are exposed to increased concentrations of methanol, the
      potential health effects of such exposures require study. Methanol, a simple
      alcohol containing one carbon atom, occurs naturally in plants and animals and
      participates in human metabolism. People regularly consume low doses of methanol
      in fruits, vegetables, and fermented beverages as well as soft drinks and foods
      sweetened with aspartame (which breaks down to methanol in the gastrointestinal
      tract). Despite its ubiquitous presence, methanol can be highly toxic if
      sufficient quantities are consumed. Ingestion of methanol (usually in the form of
      wood alcohol or tainted alcoholic beverages) can result in metabolic acidosis,
      blindness, and even death. Although the body has the capacity to metabolize the
      low doses of methanol to which people are regularly exposed, it cannot handle
      high doses because too much methanol overwhelms the body's ability to remove a
      toxic metabolite (formate). When formate accumulates, methanol poisoning occurs.
      One factor that regulates the rate at which formate is removed is the liver level
      of a derivative of the vitamin folic acid. People who are deficient in folic acid
      (including 15% to 30% of pregnant women) may be particularly susceptible to the
      toxic effects of methanol. If methanol were to be widely adopted as a fuel,
      environmental exposures would increase through ingestion of contaminated drinking
      water, inhalation of vapors from evaporative and other emissions, and dermal
      contact. Current concentrations of methanol in ambient air are very low, 1 to 30
      parts per billion (ppb). If all motor vehicles in the United States were
      converted to 100% methanol fuel, methanol levels in ambient air are estimated to
      increase approximately 1,000-fold (to 1 to 10 ppm in cities) and in a worst-case
      situation could occasionally reach concentrations as high as 200 ppm in enclosed
      spaces (HEI 1987). Inhaling these concentrations of methanol for short periods of
      time is not predicted to affect formate production and thus should not present a
      health risk. However, little is known about the consequences of long-term
      inhalation of methanol vapors, especially in susceptible populations of pregnant
      women and developing fetuses. HEI, therefore, developed a research program to
      address this information gap. APPROACH: Dr. Thomas Burbacher and colleagues of
      the University of Washington studied the effects of long-term exposure to
      methanol vapors on metabolism and reproduction in adult female monkeys (Macaca
      fascicularis) and developmental effects in their offspring, who were exposed
      prenatally to methanol. The investigators exposed adult female monkeys (11 to 12
      animals/group) to one of four concentrations of methanol vapors (0, 200, 600, and
      1,800 ppm) for 2.5 hours a day, seven days a week during the following periods:
      (1) before breeding, (2) during breeding, and (3) during pregnancy. They
      collected blood from the adults at regular intervals to monitor methanol levels
      (which served as a marker of internal dose) and formate concentrations. They also
      conducted pharmacokinetic studies to determine whether methanol disposition
      (which includes absorption, distribution, metabolism, and excretion) was altered
      as a result of repeated methanol exposures and to assess pregnancy-related
      changes. Because high doses of methanol damage the central nervous system, the
      infants (8 to 9 animals/group) were examined at regular intervals during the
      first nine months of life to assess their growth and neurobehavioral development.
      RESULTS: Exposure to methanol vapors did n

PMID- 10941407
TI  - Some physiological and psychophysiological signs of neuroticism level in healthy
      persons.
AB  - OBJECTIVE: To study cardiac reactivity on presentation of cardiotropic drug
      odour, perception of this odour and autonomic nervous system activity in high
      personality neuroticism healthy women. DESIGN: Cross sectional. SUBJECTS: 28
      healthy female undergraduate university student volunteers in the age range 21 to
      29 years. MAIN OUTCOME MEASURES: Eysenck Personality Questionnaire, threshold of
      nicethamidum odour detection, statistical parameters of electrocardiographic R-R
      intervals variance, Strain Index of cardiac regulatory systems (as a measure of
      the balance between sympathetic and parasympathetic system activities). RESULTS:
      Six subjects with low neuroticism level (LNL) and eight persons with high
      neuroticism level (HNL) were selected out of 28 young women volunteers using the
      Eysenck Personality Questionnaire. Baseline cardiac rhythm of the HNL group had a
      high level of stability and high values of the Strain Index which are
      characteristic of increased activity of the sympathetic nervous system. Increased
      variability of the cardiac rhythm and low values of Strain Index indicated
      elevated parasympathetic nervous system activity in LNL persons. HNL subjects
      also had low cardiac reactivity on presentation of nicethamidum solutions and
      high detection thresholds of odour stimuli. CONCLUSIONS: High neuroticism level
      in healthy females affects the balance between sympathetic and parasympathetic
      nervous system activities, cardiac reactivity on presentation of nicethamidum
      odour as well as perception of this odour. Low cardiac responsiveness to
      stimulatory effect of cardiotropic drug and increased sympathetic nervous system
      activity should be taken into consideration when planning treatment of neurotic
      subjects.

PMID- 10941409
TI  - Factors influencing timing of seeking health care among patients with sexually
      transmitted diseases in Kampala, Uganda.
AB  - OBJECTIVE: To identify predictors for timing of seeking health care among
      patients with sexually transmitted diseases (STDs). DESIGN AND SETTING: A cross
      sectional study at the old Mulago hospital STD clinic in Kampala the capital city
      of Uganda. SUBJECTS: A convenience sample of 138 patients with STDs were
      interviewed on social-demographic, STD symptoms, health seeking behaviour, condom
      use, sexual behaviour, and knowledge about STDs. MAIN OUTCOME MEASURES: Early
      seekers (who sought care before 14 days) and late seekers (who sought care > or =
      14 days of symptoms) were compared on the above variables using bivariate and
      multivariate logistic regression analyses. RESULTS: On multivariate analysis,
      only two variables, having sex at least once during the period with symptoms (OR
      7.27; 95% CI 3.02 to 17.51) and not having sex with a casual partner in the last
      three months (OR 3.23; 95% CI 1.14 to 9.09) predicted late seeking of health
      care. CONCLUSIONS: Having sex at least once while symptomatic is a strong
      predictor of delay in seeking care and may be related to severity of symptoms.
      There is need to strengthen health education messages about the importance of
      seeking care immediately no matter how minor the symptoms. More research is
      needed to identify predictors for having sex while symptomatic.

PMID- 10941408
TI  - Risk awareness of HIV/AIDS among commercial farm workers in Zimbabwe.
AB  - OBJECTIVE: To determine levels of perceived risk of HIV infection and the
      determinants of these perceptions among commercial farm workers. DESIGN: Cross
      sectional. SETTING: Commercial farms in Manicaland, Mashonaland Central,
      Mashonaland West and Mashonaland East provinces of Zimbabwe. SUBJECTS: 406 male
      and 411 female adults. MAIN OUTCOME MEASURES: Perceived risk of HIV infection.
      RESULTS: Out of 33 female respondents aged less than 20 years, 19 (57.6%)
      reported that they had no chance of acquiring the HIV infection. The majority
      (15) of these 19 teenagers indicated that they had no chance of being HIV
      infected because they had sex only with their spouses. Of the respondents aged 20
      years or more, 235 (64.6%) males and 182 (55.3%) females reported that they had
      no chance of being HIV infected (OR = 1.47, 95% CI 1.07 to 2.02, p = 0.016). Most
      males (57.0%) and females (59.9%) of age 20 years or more said that they had no
      chance of being HIV infected because they had sex with only their spouses. Among
      the respondents of age 20 years or more who indicated they had a moderate to high
      chance of being infected or were already infected, 35 (33.3%) of the males
      reported that they had multiple partners and 41 (40.6%) of the females reported
      that their spouses had multiple partners. CONCLUSION: In general, despite high
      seroprevalence rates in Zimbabwe, many individuals do not perceive themselves at
      risk. Future health education intervention studies should seek to increase the
      general perception of low risk so that adequate precaution can be taken against
      being infected.

PMID- 10941410
TI  - Supernumerary molar teeth: observations in the skulls.
AB  - OBJECTIVE: To study the prevalence of supernumerary molar teeth in the skull
      collection of the Zimbabwe Museum of Human Sciences. DESIGN: Cross sectional
      anatomical observations on human skulls. SETTING: Zimbabwe Museum of Human
      Sciences, Harare, and the Department of Anatomy, University of Zimbabwe, Mount
      Pleasant, Harare. SUBJECTS: 153 skulls with intact maxillae and 112 mandibles
      from the skeletal collections of the Zimbabwe Museum of Human Sciences
      representing the Black Zimbabwean population. MAIN OUTCOME MEASURES: Observations
      on the presence and location of supernumerary molars in the upper and the lower
      jaws of the human skulls as well as the diameters of supernumerary molars.
      RESULTS: Two fourth molars were observed in two upper jaws and their prevalence
      was 0.76%. One fully erupted fourth molar was observed on the left side of the
      upper jaw distal to the third molar in the alveolar arch of the female skull aged
      40 years. Another impacted fourth molar was observed on the right side of the
      upper jaw of the female aged less than 25 years and was present on maxillary
      tuberosity. No fourth molars were observed in lower jaw collections. CONCLUSIONS:
      It appears that the supernumerary molars occur rarely. It would be appropriate to
      evaluate the prevalence of supernumerary teeth in Zimbabwean population based on
      clinical and radiological examination rather than observations in the skulls.

PMID- 10941411
TI  - Primary renal carcinoid: report of a case.
AB  - A 28 year old female presented with a right renal mass. She was treated with a
      radical nephrectomy. Histologically the tumour revealed the classical appearance
      of a carcinoid. The opposite kidney contained a multilocular cystic renal cell
      carcinoma. The histogenesis of a renal carcinoid is discussed.

PMID- 10941412
TI  - Progress towards polio eradication in Zimbabwe.

PMID- 10941413
TI  - Pharmacogenomics: today, tomorrow and beyond.

PMID- 10941414
TI  - Are Bartonella significant emerging pathogens in southern Africa?

PMID- 10941415
TI  - Genetic analysis of interferon and other mammalian signaling pathways.
AB  - Systematic forward genetics, so powerful for analyzing pathways in haploid
      organisms, has contributed much less to our understanding of diploid mammalian
      cells. With Ian Kerr, we have used regulated expression of selectable markers in
      heavily mutagenized cells to isolate mutant mammalian cell lines defective in
      eight different proteins required for interferon signaling. These cells have been
      valuable in studying the roles of the deleted Janus Kinase (JAK), signal
      transducer and activator of transcription (STAT), and receptor proteins in
      interferon and other signaling pathways. Mutant cells defective in the induction
      of class II major histocompatibility complex (MHC) antigens by interferon-gamma
      or in repressing interferon-regulated genes have also been obtained. More
      recently, mutant cells unresponsive to double-stranded RNA, tumor necrosis factor
      alpha (TNF-alpha), or interleukin-1 (IL-1) have been isolated and characterized
      and a mutant line defective in expressing the tumor suppressor protein p53 has
      also been obtained. Systematic forward genetics can now be applied more easily to
      mammalian cells, to help elucidate signaling pathways.

PMID- 10941416
TI  - Form from function in visual system development.

PMID- 10941417
TI  - Genes and genomes.

PMID- 10941418
TI  - Signals for tissue induction and organ formation in vertebrate embryos.

PMID- 10941419
TI  - Probing the intracellular life of bacteria.

PMID- 10941420
TI  - DNA and RNA polymerases: structural diversity and common mechanisms.

PMID- 10941421
TI  - In vitro selection and directed evolution.

PMID- 10941422
TI  - Hypertension and related risk factors in type 2 diabetes mellitus.
AB  - METHODS: The correlation between hypertension and related risk factors has been
      studied in 733 type 2 diabetic patients. Hypertension was more frequent in women
      (65.35%) than in men (50.35%) (p < 0.0001). RESULTS: Hypertensive patients showed
      older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than
      normotensive. In the diabetic group on diet only basal insulinaemia was higher (p
      < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such
      a difference, was not seen in patients of both sexes treated with oral
      hypoglycaemic agents; besides there was no difference in fasting C-peptide levels
      between hypertensive and normotensive insulin treated patients. In both sexes
      hypertension was independently correlated with age, BMI, increased urinary
      albumin excretion, triglycerides. The strongest correlation was with the family
      history of hypertension. On the contrary there was no correlation between
      hypertension and waisthip ratio. CONCLUSIONS: In conclusion, the association
      between hypertension and type 2 diabetes depends on various risk factors, but a
      relationship with insulin levels is not surely demonstrable.

PMID- 10941423
TI  - IGF-1 and IGFBP in congenital and acquired hypothyroidism after long-term
      replacement treatment.
AB  - BACKGROUND: Thyroid hormones are involved in the regulation of the GH/IGF axis.
      Hypothyroidism is associated with a reduction in GH pulsatility and in GH
      response to stimulatory tests. In hypothyroidism, serum levels of IGF-1 and IGFBP
      3 fall and these changes are reversed after short term replacement with L-T4.
      This study was undertaken to determine the effect of long term replacement
      therapy with T4 in IGF-1 and IGFBP-3 serum levels. METHODS: The study included 12
      patients affected with hypothyroidism and in replacement treatment with T4. They
      were divided into 3 groups according to age at the beginning of treatment. Group
      A consisted of 4 pre-pubertal subjects with Congenital Hypothyroidism (CH)
      diagnosed with neonatal screening, where T4 treatment was started within 15 days
      of life. Group B consisted of 5 young adults where CH was clinically diagnosed at
      the median age of 6 months and replacement therapy started at this age. Group C
      consisted of 3 subjects affected with hypothyroidism secondary to thyroiditis
      where diagnosis and replacement treatment were delayed at age 11, 12 and 14
      respectively. All subjects were matched with a control of the same age, sex,
      weight and pubertal stage. RESULTS: FT3, FT4 and TSH were in the normal range
      both in patients and in controls. No correlation was found between FT3 or FT4 and
      IGF-1 or IGFBP-3 serum levels. IGF-1 serum levels in group A (198 +/- 122 ng/ml)
      were significantly lower than that in group B (624 +/- 105, p < 0.001) and in
      group C (649 +/- 98, p = 0.003). IGFBP-3 serum levels in group A (1.98 +/- 0.56
      micrograms/ml) were significantly lower than in group B (3.65 +/- 1.10, p = 0.03)
      and in group C (4.13 +/- 0.49, p = 0.003). The increase in IGF-1 and IGFBP-3
      levels was seen also in control groups B and C when compared with control group
      A. IGF-1 and IGFBP-3 were positively correlated with age both in patients and in
      controls. A linear correlation was found between IGF-1 and IGFBP-3 which was
      positive for controls (r = 0.946, p < 0.001) and patient group A and B (r =
      0.839, p = 0.005) but tended to be negative for patient group C (r = -0.65,
      n.s.). CONCLUSIONS: Our data demonstrate that long term replacement therapy in
      children with hypothyroidism is associated with a physiological increase in IGF-1
      and IGFBP-3. The positive correlation between IGF-1 and IGFBP-3 levels in group A
      and B confirm the efficacy of long term replacement treatment on the IGF-1/BP-3
      axis in pre- and post-pubertal patients treated for CH. However, this correlation
      tended to be negative in patients with hypothyroidism secondary to thyroiditis,
      suggesting that the cause of thyroid insufficiency and/or the age at the
      beginning of replacement therapy may have a role in the post-pubertal hormonal
      status in IGF-1 and IGFBP-3 balance.

PMID- 10941424
TI  - IGF-1 levels in different conditions of low somatotrope secretion in adulthood:
      obesity in comparison with GH deficiency.
AB  - BACKGROUND: It is widely accepted that IGF-I synthesis and release depend on GH
      secretion as well as on the nutritional status and vary with age. Based on these
      premises, after the definition of normal IGF-I levels during lifespan, in a large
      population of normal subjects of both sexes, our aim was to verify IGF-I levels
      in large groups of adult patients with GH deficiency or obesity, a condition in
      which a reduced somatotrope secretion is well known. METHODS: To this goal, IGF-I
      levels were assayed after acid-ethanol extraction, in 326 normal subjects (NS, 98
      men and 228 women, age 20-80 yrs, BMI 17.9-26.1 kg/m2), 54 patients with GH
      deficiency (GHD, 24 men and 30 women, age 20-80 yrs, BMI 18.2-27.1 kg/m2), and
      195 patients with obesity (OB, 33 men and 162 women, age 17-71 yrs, BMI 27.7-64.9
      kg/m2). In NS, IGF-I levels were similar in both sexes and showed a progressive
      decrease with age. No correlation was present between IGF-I and BMI in NS. Median
      IGF-I levels and the 3rd centile in NS when considered per decade were: III) 230
      and 108.6; IV) 220 and 129.8; V) 150.5 and 72.4; VI) 163.0 and 62.4; VII) 110 and
      41.6; VIII) 82 and 24.7 micrograms/l. In GHD, IGF-I levels were independent on
      sex and did not show reduction during lifespan. Mean IGF-I levels in GHD were
      lower than that in NS (64.5 +/- 5.9 vs 171.3 +/- 4.8 micrograms/l, p < 0.01) and
      did not correlate with age or BMI. Analyzing individual IGF-I levels, in GHD, in
      the III and IV decade 21/24 patients had IGF-I levels lower than 3rd centile
      while, up to the VIII decade, only 10/30 had IGF-I levels below normal limits. In
      OB, IGF-I levels were independent on sex but, like in NS, showed a progressive
      decrease with age and were independently, negatively correlated with BMI but not
      with WHR. Analyzing individual IGF-I levels, in OB, IGF-I levels were below 3rd
      centile in 10/77 patients in the III and IV decade and in only 8/108 patients up
      to the VIII decade. Mean IGF-I levels in the whole OB population (179.6 +/- 5.9
      micrograms/l) were higher (p < 0.01) than those in GHD (64.5 +/- 5.9
      micrograms/l) while only in the IV decade IGF-I levels in OB group were lower (p
      < 0.02) than those in NS (184.7 +/- 12.6 micrograms/l vs 224.0 +/- 9.2
      micrograms/l). CONCLUSIONS: In conclusion, present data confirm that IGF-I levels
      depends on GH secretion as well as on nutritional status, being negatively and
      independently correlated with age and BMI. IGF-I assay is not a reliable test for
      the diagnosis of GH deficiency in adulthood though it gives good discrimination
      between GHD and normal subjects up to 40 yrs of age. In spite of low GH
      secretion, IGF-I levels are only slightly reduced in obesity, probably as
      consequence of hyperinsulinism.

PMID- 10941425
TI  - [The use of FSH in adolescents and young adults with idiopathic, unilateral, left
      varicocele not undergoing surgical intervention. Preliminary study].
AB  - BACKGROUND: To study gonadal function in young patients suffering from left
      varicocele. METHODS:  DESIGN: prospective study. SETTING: university laboratory
      and clinical services. PATIENTS: 20 boys (age range: 15-20 yrs; mean +/- DS: 17.9
      +/- 1.48 yrs), affected by left idiopathic varicocele. INTERVENTION: high
      purified urinary FSH s.c. (Metrodin HP 75, Ares-Serono), three times every week,
      for three months. MAIN OUTCOME MEASURES: seminal fluid examination before and
      after therapy (WHO). RESULTS: At the end of the study period a statistically
      increase of sperm density/ml (38.45 x 10(6) vs 49.10 x 10(6), total sperm
      number/ejaculate with forward motility (37.41 x 10(6) vs 48.52 x 10(6)) and a
      decrease of atypical forms (54.35% vs 49.60%) has been observed; the increase of
      the total sperm number/ejaculate after FSH treatment greater than 50% compared
      with basal values allows to define 9 patients as responders. CONCLUSIONS: In this
      study the FSH treatment in young people with varicocele leads to a statistically
      significant increase in the seminal fluid parameters and may characterize a group
      of patients who may have a better prognostic outcome regarding the tubular
      gonadal function and thus the fertility potential in adult life.

PMID- 10941427
TI  - Physiopathology of the renin-angiotensin system in the ovary.
AB  - The present review confirms the existence of the so-called "ovarian-derived
      prorenin-angiotensin cascade". It also describes the physiopathology of the
      system and, consequently, its role in the genesis of phenomena concerning
      reproductive function such as ovulation, steroid synthesis and folliculogenesis.
      Moreover, the "ovarian-derived prorenin-angiotensin cascade" appears to play an
      important role in the aetiopathogenesis of diseases such as ovarian tumours,
      ovarian hyperstimulation syndrome and ectopic pregnancy.

PMID- 10941428
TI  - [Biologically inactive growth hormone].

PMID- 10941426
TI  - [Nutritional status, obesity, and metabolic balance in pediatric patients with
      type I diabetes mellitus].
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate the nutritional status
      of children with type 1 diabetes and to search for possible influences of changes
      in body composition on aspects of diabetes. METHODS: A group of 96 diabetic
      subjects (41 males and 55 females) were studied, aged between 3 and 19 years old.
      The following parameters were examined: weight, stature, 5 skin folds, 7
      circumferences, bioelectric impedance, arterial pressure, cholesterolemia,
      triglyceridemia, insulin dose, HbA1c and duration of disease. RESULTS: Obesity
      and overweight were present in 34.5% of the sample, but obesity was only observed
      in females (25.5%). There was also a high percentage of underweight subjects
      (11.5% of the entire sample). The mean values of weight BMI, 5 skin folds, 4
      circumferences, FM (calculated using fold measurement and BIA) and AFA were
      higher in females, whereas mean values of waist/hip ratio and waist/thigh ratio
      and FFM (in % of body weight) were higher in males. A close correlation was also
      found between the 4 weight classes (underweight, normal weight, overweight,
      obese) and the majority of marker parameters for adiposity (5 folds, 4
      circumferences, BIA, FM calculated using BIA, fold measurement and AFA). Of the
      other parameters examined (mean duration of disease, HbA1c assay, daily insulin
      dose, total cholesterolemia, triglycerididemia, arterial pressure), only the
      daily insulin dose showed higher values in females in 3 weight classes
      (underweight, normal weight and obese). Following a comparison with the control
      population (2469 subjects), higher mean values were found in the latter compared
      to diabetic subjects, but only in relation to 3 skin folds (tricipital,
      subscapular and suprailiac) and one circumference (forearm). CONCLUSIONS: The
      study shows a high frequency of overweight and obesity in children with type 1
      diabetes, comparable to that in the healthy population. The finding of a higher
      frequency of obesity in diabetic females might be explained by their advanced
      puberal status, given that almost all the obese diabetic females were aged
      between 10 and 19 years old. The study confirms the validity of a number of
      anthropometric measurements (BMI, folds, circumference) and BIA in the evaluation
      of nutritional status in terms of body composition.

PMID- 10941429
TI  - Congenital hypopituitarism in a 48-year old adult. Natural course, hormonal study
      and MRI evidence.
AB  - A case of Congenital Hypopituitarism (CH) in an untreated 48 yr-old-man is
      reported. The hormonal studies demonstrated a panhypopituitarism and MR imaging
      revealed absence of pituitary stalk, small anterior pituitary remnant on the
      sella floor and ectopic neurohypophysis at the tuber cinereum. The pattern of
      hormonal responsiveness suggests that CH encompasses findings typical of primary
      anterior pituitary disease and those of hypothalamic dysfunction.

PMID- 10941430
TI  - A case of primary hydatidosis of the thyroid gland.
AB  - A 54-year-old woman presented with an expansive mass in the anterior cervical
      region (front of the neck) with abscess. Laboratory tests and thyroid profile
      proved normal. Surgical exploration revealed a hydatid cyst in the left lobe of
      the thyroid gland with parasitic metastasis of the left lateral cervical lymph
      node chain. Postoperative examination of the nodule showed it to be a solitary
      primary thyroid hydatid cyst.

PMID- 10941431
TI  - [Bullous dermatitis self-induced].
AB  - In three patients, two women aged 37 and 20 years and a man aged 46 years, a
      blistering skin condition was observed. Histopathological examination of the skin
      lesions revealed a blister level just beneath the stratum granulosum, which is
      proof of a friction blister. The patients were suffering from bullous dermatitis
      artefacta or bullous pathomimia. This is a psychiatric disorder characterised by
      rubbing skin blisters but denying self-infliction. Early diagnosis is important
      to prevent unnecessary drug therapy and chronic morbidity. The typical histology
      supports the doctor in his suspected diagnosis. A supportive and empathic dual
      disciplinary approach (by somatic physician and psychosocial worker) is
      recommended, avoiding direct confrontation with the self-inflicted nature of the
      lesions, and using the 'narrow escape' strategy, avoiding loss of face of the
      patient.

PMID- 10941432
TI  - [Cognitive impairment and dementia in hypertension; the effect of
      antihypertensive medication].
AB  - The prevalence and incidence of both degenerative (Alzheimer) and vascular
      dementias rise exponentially with aging. In both forms of dementia hypertension
      is a predisposing factor. The interval between the onset of hypertension and the
      manifestation of dementia amounts to 12-15 years. A complicating factor is the
      observation that initial dementia may be accompanied by secondary decrease in
      blood pressure. A preventive effect of current antihypertensive treatment is
      likely, according to preliminary evidence (particularly with regard to the use of
      the calcium antagonist nitrendipine), but the hopeful perspective of protection
      against dementias through antihypertensive treatment remains to be confirmed by
      further prospective comparative trials.

PMID- 10941433
TI  - [Immunology in the medical practice. XXXI. Hereditary immune deficiencies:
      relationship between clinical symptoms and abnormalities of the immune system].
AB  - Severe congenital immunodeficiency diseases occur in approximately 1:10,000
      newborns, in Western Europe and North America. They are characterised by
      recurrent infections, mostly caused by opportunistic micro-organisms, and
      autoimmune phenomena. In many patients the immune deficiency occurs as part of a
      syndrome. An immunological dysfunction may be caused by total absence, strong
      reduction or dysfunction of one or more cellular elements or of cell-associated
      or cellular secretion products. It is convenient to divide the immune system into
      a cellular compartment (with specific T and B cells, and non-specific natural
      killer cells and myelomonocytes), a compartment for cellular interactions
      (adhesion, costimulation and communication through cytokines) and an aspecific
      opsonization compartment. In cases of deficient humoral immunity treatment
      options are antimicrobial drugs and substitution therapy with immunoglobulins, in
      cases of phagocytic dysfunction the application of intracellularly active
      antibiotics and in cases of disturbances of cellular immunity allogeneic
      transplantation of haematopoietic stem cells and in the future perhaps the repair
      of the genetic defect by somatic gene therapy.

PMID- 10941434
TI  - [Clinical thinking and decision making in practice. A patient with persistent
      fever].
AB  - A 20-year old man was admitted to hospital with fever and malaise after travel to
      India. He was soon found to have typhoid fever, caused by a multi-drug resistant
      Salmonella typhi. According to in-vitro resistance testing he was treated with
      cefotaxim, but fever and shivering were still present after 7 days of cefotaxim,
      with liver enzyme disturbances. The physicians caring for him started an
      extensive search for possible complications of typhoid fever, and they thought of
      the possibility of an alternative disease to explain the fever. When cefotaxim
      was stopped all symptoms and signs disappeared. During every medication, drug
      fever is a possibility. This diagnosis can only be supported by discontinuing the
      use and if necessary, restarting it (dechallenge and rechallenge).

PMID- 10941436
TI  - [Chronic low back pain: exercise therapy, multidisciplinary programs, NSAID's,
      back schools and behavioral therapy effective; traction not effective; results of
      systematic reviews].
AB  - OBJECTIVE: To inventory the current state of the art regarding the effectiveness
      of conservative treatment of chronic low back pain. DESIGN: Systematic reviews.
      METHOD: The relevant literature from the period January 1966-September 1999 was
      retrieved via Medline, Embase, PsychLit and the Cochrane Library and via
      reference lists in the articles found. The methodological quality of the studies
      was assessed using criteria for internal validity. On the basis of the number of
      examinations, their quality and the consistency of the findings, conclusions were
      subdivided into four levels of strength of scientific evidence. RESULTS: There
      was strong evidence that exercise therapy and multidisciplinary treatment
      programmes were effective in chronic low back pain, and moderate evidence that
      non-steroidal anti-inflammatory drugs (NSAIDs), back schools and behavioural
      therapy were effective in chronic low back pain. There was also strong evidence
      that traction was not effective in chronic low back pain. Strong evidence for
      effectiveness of many other commonly used interventions was lacking.

PMID- 10941435
TI  - [Acute low back pain: activity, NSAID's and muscle relaxants effective; bedrest
      and targeted exercise not effective; results of systematic reviews].
AB  - OBJECTIVE: To inventory the current state of the art regarding the effectiveness
      of conservative treatment of acute low back pain. DESIGN: Systematic reviews.
      METHOD: The relevant literature from the period January 1966-September 1999 was
      retrieved via Medline, Embase, Psychlit and the Cochrane Library and via
      reference lists in the articles found. The methodological quality of the studies
      was assessed using criteria for internal validity. On the basis of the number of
      examinations, their quality and the consistency of the findings, conclusions were
      subdivided into four levels of strength of scientific evidence. RESULTS:
      Approximately two-thirds of the randomised trials in the field of back pain were
      of poor methodological quality. There was strong evidence that advice to stay
      active, non-steroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants were
      effective in acute low back pain. There was also strong evidence that bed rest
      and specific exercises were not effective in acute low back pain. Strong evidence
      for effectiveness of many other commonly used interventions was lacking.

PMID- 10941437
TI  - [Septic arthritis in two young children caused by unusual gram-negative
      pathogens].
AB  - Two children, a girl aged 2 years and a boy aged 10 months, were moderately ill
      with signs of inflammation of the left and the right knee, respectively. Both had
      had pharyngitis, and the boy also had paronychia of the right foot. The Gram
      preparation of synovial fluid showed Gram-positive cocci in the girl, while
      Kingella kingae was cultured. In the boy, a Moraxella was cultured from the
      synovial fluid using an aerobic blood culture system. Both recovered without
      sequelae after adequate antibiotic treatment. The micro-organisms cultured were
      Gram-negative bacteria, which are rarely seen in septic arthritis and are
      difficult to demonstrate. In young children, septic arthritis often presents with
      mild symptoms and inconclusive laboratory findings. Even if the Gram preparation
      of the synovial fluid shows no micro-organisms, unusual pathogens may be isolated
      by means of an aerobic blood culture system.

PMID- 10941438
TI  - Cross-species amplification, non-invasive genotyping, and non-Mendelian
      inheritance of human STRPs in Savannah baboons.
AB  - Twenty-nine human microsatellite primer pairs were screened for their utility in
      the cross-species amplification of baboon DNA derived from both blood and feces
      as part of a larger study to identify paternal half sisters in a population of
      wild baboons (Papio cynocephalus). Forty-one percent (12/29) of the human primers
      successfully amplified baboon DNA. Of these 12 primers, six amplified fragments
      that were both polymorphic and heterozygous (mean number of alleles = 6, mean
      heterozygosity = 87%) and yielded repeatable results. However, only five of these
      six simple tandem repeat polymorphisms (STRPs) showed patterns of Mendelian
      inheritance (i.e., mothers and offspring shared at least one allele at each
      locus), and were therefore useful for determining relatedness between
      individuals. Analysis of the sixth primer revealed non-Mendelian inheritance,
      i.e., three of the six known mother-daughter pairs had no shared alleles. This
      failure was probably due to non-specific fragment amplification, and may have
      resulted from a different STRP locus being amplified in mother and daughter. This
      finding highlights the importance of sampling DNA from known parent-offspring
      pairs when screening microsatellite primers for genetic studies. Multiple,
      independent replications of genotypes and Mendelian checks are both particularly
      important when using cross-species amplification or when using a low-quality
      source of DNA.

PMID- 10941439
TI  - Lifetime reproductive success, longevity, and reproductive life history of female
      yellow baboons (Papio cynocephalus) of Mikumi National Park, Tanzania.
AB  - The relationship between longevity and lifetime reproductive success (LRS) was
      studied in free-ranging female baboons of Mikumi National Park, Tanzania. A
      severe population decline occurred between the 12th and 20th years of the study.
      The total sample consisted of 72 females born and reaching adulthood before the
      start of the population decline. There were 27 females who were adult at the
      start of the study and 45 who became adult within the 12 years prior to the
      decline. The subjects were studied until all 72 were dead and all of their
      offspring were either dead or at least six years old; this took 24 years. The
      relationship of longevity to LRS was statistically significant for the total
      sample and for both sub-samples, with 70% of the total variance in LRS accounted
      for by longevity. Longevity was linked to LRS via a chain of statistically
      significant relationships: The longer the life span, the longer the reproductive
      life; the longer the reproductive life, the more offspring produced; the more
      offspring produced, the higher the LRS. Mean LRS, life span, and reproductive
      longevity all differed between the two sub-samples. Since the sub-samples were
      time-linked to a population decline affecting longevity, either sub-sample
      separately would fail to reflect the broader picture. This illustrates the
      importance of appreciable sample sizes from long-term studies in helping
      understand the dynamics between life history estimates and ecological conditions
      in variable environments.

PMID- 10941440
TI  - Death of a wild chimpanzee community member: possible outcome of intense sexual
      competition.
AB  - Our observations strongly support the view that a lethal gang attack occurred
      against a young adult male within a wild chimpanzee (Pan troglodytes
      schweinfurthii) community. This is the first report of such an occurrence. At
      least three adult male chimpanzees are believed to have been involved in the
      attack. This case is unusual because the attack was fatal, involved directed
      group aggression within a community, and was not linked to the overthrow of the
      alpha male. During the period before the attack, the percentage of cycling
      females in the community was very low (15 males:17 females, a maximum of two
      regularly cycling). This fact, coupled with the presence of one female in full
      genital tumescence, may have incited and escalated the violence of the attack.
      The lethal attack is interpreted as an act of intra-community male sexual
      competition resulting in the complete exclusion of one male from estrous females.

PMID- 10941441
TI  - Genetic comparison between different populations of Eulemur macaco flavifrons in
      northwest Madagascar using RAPD markers.
AB  - Eulemur macaco flavifrons, the Sclater's black lemur, is a critically endangered
      subspecies of northwest Madagascar, which is not yet protected by any reserve. In
      order to study the feasibility of creating such a reserve, an area of outstanding
      biological importance was selected in the region of Maromandia-Sahamalaza, which
      is probably the only remaining place which would permit the long-term survival of
      the Sclater's black lemur. To determine if genetic management is needed for the
      Sahamalaza black lemur population, its genetic variability was estimated with
      random amplified polymorphic DNA (RAPD) markers and compared with other
      populations. These comparisons demonstrate that the Sahamalaza black lemurs have
      a genetic variability equivalent to those in other areas. Thus, we conclude that
      no genetic management is required at the present time.

PMID- 10941442
TI  - Urinary progesterone in free-ranging red howler monkeys (Alouatta seniculus):
      preliminary observations of the estrous cycle and gestation.
AB  - The goals of this study were to develop and validate a radioimmunoassay (RIA) for
      measurement of unconjugated progesterone (P) concentrations in the urine of red
      howler monkeys (Alouatta seniculus) and to use urinary P profiles to characterize
      the reproductive cycle of this species. Analysis of P profiles from two females
      provided a preliminary estimate of the length of the estrous cycle (mean days +/-
      S.E.M. = 29.5 +/- 1.5; n = 2), and indicated that one female red howler copulated
      throughout two apparent estrous cycles. Urinary P concentrations during two
      confirmed pregnancies (211.8 +/- 29.7 ng P/ml) were higher (P < 0.05) than during
      the luteal phase (77.4 +/- 10.6 ng P/ml; n = 4) of the cycle.

PMID- 10941443
TI  - Seasonality of matings and births in captive Sichuan golden monkeys
      (Rhinopithecus roxellana).
AB  - This study, based on three years of mating behavior observations and 10 years of
      birth records, reveals that Sichuan golden monkeys in captivity displayed a
      marked seasonality of mating behavior and births. The peak of matings occurred
      around October, and births occurred in March-June. The birth peak followed the
      mating peak by six to seven months. This seasonal cycle of matings and births was
      similar to observations made in the wild, where both temperature and food
      resources were favorable in spring. The time delay between peaks of matings and
      births was the approximate length of gestation, which implies that mating
      behavior was concentrated during the period of conception. We suggest that the
      peak of births in captive Sichuan golden monkeys occurred during the time of year
      with the most favorable environmental conditions, and the peak of matings
      corresponded with the period of conception.

PMID- 10941444
TI  - [Severe obstetric complications nescessitating hospitalization and intensive
      care: a ten year retrospective study].
AB  - OBJECTIVES: To assess the serious maternal morbidity during pregnancy, delivery
      and post partum, which led to an hospitalization in a medical or surgical
      intensive care unit. STUDY DESIGN: A Retrospective study was carried out on a
      period of ten years, from July 1986 to July 1996, in the University Teaching
      Hospital of Besancon. PATIENTS: The criterions of inclusion come from the
      definition of the serious maternal morbidity decided by the Inserm: any admission
      of a pregnant woman in a medical or surgical intensive care unit in the 42 days
      of the post-partum, whatever the term of the pregnancy and the type of the post
      partum, extra uterine pregnancy, spontaneous miscarriage and medical or voluntary
      abortion. METHODS: Forty-six patient's medical file hospitalized in a medical or
      surgical intensive care unit between July, 1st 1986 and July, 31st 1996, have
      been studied. RESULTS: The analysis of the cause underline the gravity of the
      pathologies handled with young patients and initially healthy, the short length
      of controlled ventilation and hospitalization, the avoidability of great number
      of transfer in an intensive care unit, and the lack of hospitalization due to
      anaesthesia. The frequency of hospitalisation in an intensive care unit during
      and after the pregnancy was estimated at 0.17% of lives births. CONCLUSION: The
      serious maternal morbidity could be an indicator of the quality of the obstetrics
      cares which would complete the study of the maternal mortality. The potential
      gravity of the complication of the pregnancy and the delivery require better care
      of this patients.

PMID- 10941445
TI  - [Risk factors for mortality in abdominal aortic surgery].
AB  - OBJECTIVE: To analyse pre and peroperative variables for predicting mortality
      after abdominal aortic surgery. STUDY DESIGN: Prospective study. PATIENTS: We
      prospectively included 658 consecutive patients undergoing abdominal aortic
      surgery from January 1993 to July 1997. METHODS: Age, gender, hypertension,
      history of myocardial infarction or coronary revascularization, angina pectoris,
      diabetes, arrhythmia, cardiac insufficiency, serum creatinine > 150 mumol.L-1,
      beta-blockers therapy, calcium channel inhibitors, angiotensin converting enzyme
      inhibitors were preoperative analysed variable. Type of aortic disease (anuerysms
      versus aortic occlusion), duration of surgery, blood loss, type of laparotomy
      (medium versus lombotomy) were peroperative analysed variables. Haemoglobinemia
      was monitored during surgery and patients were transfused if haemoglobinaemia <
      80 g.L-1. RESULTS: Thirty-three patients died after aortic surgery (5%). In
      multivariate analysis, angina pectoris (OR = 5.47, P < 0.001), chronic
      obstructive bronchopulmonary disease (OR = 2.27, P = 0.05) and duration of
      surgery (OR = 1.60, P < 0.001) were the independent predictive factors of
      mortality. Age, blood loss were predictive factors only in univariate analysis.
      CONCLUSION: Angina pectoris and COBP were the two independent preoperative
      factors of mortality. The duration of surgery was the only peroperative factor.
      Well monitored blood loss was not a predictive factor.

PMID- 10941446
TI  - [Clinical evaluation of alarm efficieny in intensive care].
AB  - OBJECTIVE: To evaluate the efficiency of haemodynamic and respiratory monitoring
      system by a clinical analysis of the alarms. STUDY DESIGN: Observational
      prospective study. PATIENTS: 25 patients who presented acute respiratory distress
      syndrome and who were monitored with haemodynamic and respiratory monitoring.
      METHODS: Each minute, a bedside clinical observer analysed alarms from the
      monitoring according to detection or absence to clinical events. Four situations
      were defined to statistical descriptive analysis: a) false positive (FP); b) true
      positive (TP); c) false negative (FN); and d) true negative (TN). True positive
      alarm which induced consequences on patients care were also analysed. RESULTS:
      15,013 minutes allowed the recordings of 3,665 alarms, 44% from arterial
      pressure, 17% from SpO2 and 12% from airways maximal pressure. 46% were false
      positive alarms inducing a noisy pollution. The positive predictive value PPV =
      TP/(TP + FP) of these alarms were respectively 51% for arterial pressure, 18% for
      SpO2 and 100% for Paw. Only 5% of true positive alarms induced consequences on
      patients care. CONCLUSION: This protocol allowed the evaluation of monitoring
      efficiency. This kind of evaluation may help to improve monitoring capacity with
      reducing noisy pollution from false positive alarms.

PMID- 10941447
TI  - [Severe hyponatremic encephalopathy after pediatric surgery: report of seven
      cases and recommendations for management and prevention].
AB  - BACKGROUND: The infusion of hypotonic solutions in the perioperative period can
      lead to the development of hyponatraemic encephalopathy which is a severe, life
      threatening but preventable complication. CLINICAL PRESENTATION: Seven children
      aged 3-6 yr, ASA 1 or 2, operated on for a scheduled surgical procedure,
      presented at the 11th postoperative hour with seizures or status epilepticus,
      associated with vomiting (5/7), and a constant loss of consciousness (median
      Glasgow Coma Scale at 7), while one child presented with a respiratory arrest. At
      arrival in ICU, serum sodium was 120 mmol.L-1. All children had received in the
      perioperative period an hypotonic solution infusion (mainly dextrose 5%), at a
      high rate for most of them. Management included mechanical ventilation (3/7),
      antiepileptic drugs (7/7), fluid restriction (7/7), sodium chloride infusion
      (5/7), and diuretics (6/7). Serum sodium increased to a mean of 135 mmol.L-1 in
      12 hours. Six children had a good neurologic outcome while one child died from
      brain death. CONCLUSION: The use of hypotonic solute in the perioperative period
      can lead to hyponatremic encephalopathy, a severe neurologic complication of
      acute hyponatremia. It must be prevented by the use of appropriate solutions i-e
      isotonic fluids in regards of the low free water elimination capacities of the
      surgical patient.

PMID- 10941448
TI  - [Parasigmoid abscess revealed by anaerobic osteomyelitis].
AB  - We report the case of a 66 year-old-patient, who profited by a laminectomy T4 to
      T7 for spinal cord compression due to an osteomyelitis. Bacteriological samples
      showed positives gram cocci and Bacteroides fragilis by the culture. The
      systematic research of a primitive source permitted to find a parasigmoidis
      abscess, which was treated by a sigmoidectomy with a colorectal anastomosis.

PMID- 10941449
TI  - [Syringomyelia discovered in the course of peridural anesthesia].
AB  - Neurological symptoms after epidural anaesthesia suggest complications due to
      anaesthetic procedure. We report the case of a child who underwent perineal
      surgery in a gynaecological position under general and epidural anaesthesia, who
      experienced the day after surgery hypoesthesia of the whole left lower limb
      without any motor deficit. Magnetic resonance imaging excluded spinal
      compression, but revealed syringomyelic cavity extending from T9 to T11.
      Electromyogram evaluation was normal. Clinical signs completely vanished within
      24 hours. This case emphasizes that the apparition of neurological signs after
      central nerve blocks is not only a complication of regional anaesthesia, but may
      reveal unknown neuropathy or result from surgical position or surgical procedure.
      Meticulous neurological examination, magnetic resonance imaging and
      electromyogram are immediately required.

PMID- 10941450
TI  - [Acute acalculous cholecystitis following hepatic artery embolism in multiple
      trauma].
AB  - We have reported a case of acute acalculous cholecystitis occurring after hepatic
      artery embolization in a woman sustaining multiple traumatic injuries. Although
      many classical factors such as shock, sepsis, transfusion or narcotic
      administration may be involved in the genesis of gall-bladder necrosis, we have
      discussed the possible involvement of hepatic artery embolization in the
      ischaemic process. Indeed, this mechanism has already been reported in non
      traumatic patient following hepatic tumor chemoembolization.

PMID- 10941451
TI  - [Survey of practices of anesthetists and intensive care physicians in blood
      transfusion and blood monitoring].
AB  - In this paper, based on the results of a questionnaire, the author carried out a
      descriptive study about all the knowledges of the anaesthesists medicine on 1999
      new law of blood transfusion. This work pointed out the progress that is still to
      be done, justifying a specialized formation in transfusion for all the people
      working in anaesthesiology.

PMID- 10941452
TI  - [The "impact factor" of anesthesia and intensive care journals].
AB  - The "impact factor" (IF) of scientific journals is defined as the number of
      citations obtained over a one-year period of articles published during the two
      previous years in a journal, divided by the number of articles published in that
      journal during the preceding two years. The IF, initially devised as an indicator
      of the quality of a journal, is at present mainly considered as an indicator of
      the quality of an article contained in that journal. However the IF of a journal
      is not equivalent to the actual impact of an article. Therefore the IF is not an
      accurate tool for assessment of the scientific quality of the author of that
      article. The IFs of journals published in English are significantly higher than
      the IFs of those in another language, mainly as English is the language used for
      international communication and as English speaking authors rarely cite articles
      published in another language. The IF of the journal of the French society for
      anaesthesiology and intensive care, the Annales francaises d'anesthesie et de
      reanimation (Afar), is about seven times below the IF of Anesthesiology, which
      has the highest IF in the category "Anesthesiology". From 1992 to 1998, the
      relative impact value of the Afar has increased by 429%. However the absolute
      value remains low.

PMID- 10941453
TI  - [Unexpected occurrence of cardiac arrest during chloroquine preventive therapy].

PMID- 10941454
TI  - [Systemic arterial hypotension induced by paracetamol administration: nurse's
      anecdotes or facts from the intensive care unit?].

PMID- 10941455
TI  - [Obligations to inform patients are now the same in public and private health
      care institutions].

PMID- 10941456
TI  - [Criteria for the choice of a curare agent for prolonged administration and
      resuscitation].

PMID- 10941457
TI  - [Malignant hyperthermia and new halogen agents].

PMID- 10941458
TI  - [What anesthetic for the cirrhotic patient?].

PMID- 10941459
TI  - [A new anterior approach to the sciatic nerve].

PMID- 10941460
TI  - [Influenza virus and its variants. Physiopathology of influenza].

PMID- 10941461
TI  - [National surveillance of influenza in France: the regional influenza observation
      group].

PMID- 10941462
TI  - [Clinical specifics of influenza in the child].

PMID- 10941463
TI  - [Variability in the symptoms of influenza].

PMID- 10941464
TI  - [Post-influenza acute myositis].

PMID- 10941465
TI  - [Severe respiratory form of influenza in the child].

PMID- 10941466
TI  - [Influenza and the pregnant women].

PMID- 10941467
TI  - [Influenza in the child: risk groups].

PMID- 10941468
TI  - [Virologic diagnostics of influenza].

PMID- 10941469
TI  - [Influenza: antibiotics and other treatments].

PMID- 10941470
TI  - [Antivirals in the curative treatment of children].

PMID- 10941471
TI  - [Antivirals in influenza: mechanism of action and the resistance phenomenon].

PMID- 10941472
TI  - [Current anti-influenza vaccine utilization].

PMID- 10941473
TI  - [Recommendations for children in the case of influenza pandemic].

PMID- 10941474
TI  - [Lyme disease in Upper Normandy: report of a hospital survey].
AB  - This study presents the results of a hospital survey on Lyme disease in children
      living in upper Normandy, a region that is quite densely wooded (with 18% forest
      areas and woods). The aim of this survey was to assess the prevalence of this
      disease in children from the Seine-Maritime and L'Eure, hospitalized in pediatric
      wards in the Seine-Maritime department, which includes Rouen, Dieppe, Fecamp,
      Elbeuf, and Le Havre. Fifteen cases of Lyme disease were diagnosed between
      September 1988 and June 1997. The children (6 girls and 9 boys) were aged between
      5 and 14 years old. Only 7 subjects showed primary symptoms, while secondary
      symptoms were observed in 12 children. In the study population, a high prevalence
      (11 out of the 15 children) of neurological disorders was found. The following
      secondary symptoms were noted: 5 cases of erythema migrans, 2 cases of non
      malignant cutaneous lymphocytoma, and 4 cases which in fact had previously
      displayed primary clinical signs (3 subjects with erythema migrans and 1 subject
      with non-malignant cutaneous lymphocytoma); 7 cases of uni- or bilateral facial
      paralysis, the most frequent neurological manifestation with or without
      lymphocytic meningitis; 1 case of central vestibular syndrome with a hyperalgesic
      meningoradicular reaction in the vicinity of the tick bite; 1 case of peripheral
      radicular involvement and intense pain in the left lower limb; 4 cases of ocular
      disorders (3 diplopias, 1 bilateral conjunctivitis complicated by kerato-uveitis,
      1 bilateral complete cecitis). Only 10 child had rheumatological symptoms, i.e.,
      Lyme arthritis of the right knee. Treatment consisted of amoxicillin (10
      children) administered at a dosage of 50 to 100 mg/kg/d over a period ranging
      from 10 days to 1 month, or ceftriaxone (7 children) at a dosage of 50 to 100
      mg/kg/d administered intravenously over a period ranging from 8 days to 3 weeks.
      Two of the children received combined antibiotic therapy, and 5 subjects had
      adjunct corticotherapy.

PMID- 10941475
TI  - [Macrolides and Pseudomonas aeruginosa infection].
AB  - Several unique effects of subinhibitory concentrations of C14 and C15 macrolides
      on Pseudomonas aeruginosa infection are described in vitro: P. aeruginosa
      virulence factors inhibition, bacterial biofilm disruption, P. glycoprotein
      expression upregulation, anti-inflammatory and immunoregulatory effects. Clinical
      trials in vivo are warranted to assess the potential usefulness of macrolides for
      treatment of chronic infections caused by P. aeruginosa.

PMID- 10941476
TI  - [Viral co-infections in immunocompetent infants with bronchiolitis: prospective
      epidemiologic study].
AB  - The nature of viral infection was prospectively investigated in 202
      immunocompetent infants with bronchiolitis. Nasal aspirates were evaluated by
      immunofluorescence assay, viral isolation technique and polymerase-chain-reaction
      hybridization assay. In 55 infants (27%) more than one respiratory virus were
      detected. A Rotavirus was found in 40 infants (20%), without any relationship
      with the respiratory viral status, respiratory syncytial virus being the main
      virus (46/55), and the association of respiratory syncytial virus and adenovirus
      being the most frequent (21/55). No difference was found between monoviral
      infections on the one hand and simultaneous viral infections on the other hand
      according to age, weight, neonatal disease, past history of personal or familial
      atopy, central temperature, Silverman's index, oxygen dependency, length of
      hospitalization, microbiology data. There was no indication that simultaneous
      virus infections were associated with an increased severity of the bronchiolitis
      in immunocompetent infants.

PMID- 10941477
TI  - [Relationship between respiratory syncytial virus bronchiolitis and asthma].
AB  - Data of the literature over the last 20 years indicate that infantile asthma,
      although heterogeneous, often appears following RSV bronchiotitis, especially
      when sufficiently severe to justify hospitalisation. The risk of developing
      episodes of wheezing (bronchial obstruction syndrome) over the following 2 to 3
      years is higher than 50%, but estimations vary according to the authors.
      Functional disturbances (pulmonary distension, nonspecific bronchial
      hypperreactivity, hypoxia), with or without associated clinical symptoms, may be
      observed several months to several years after hospitalisation for bronchiolitis.
      On the other hand, mild bronchiolitis, and most of the recurrent expiratory
      obstructive syndromes with asymptomatic free intervals between episodes do not
      appear to carry a risk of functional sequelae. Children suffering from severe
      bronchiolitis usually develop a severe bronchial obstruction syndrome. In asthma,
      the percentage of IgE-dependent sensitization is less than 20% before the age of
      4 years. The presence of positive skin tests and/or specific serum IgE directed
      against the usual allergens are associated with the persistence of asthma during
      the childhood. Similarly, the appearance of wheezing after the age of 3 years (or
      recurrence after this age) is associated with the persistence of asthma.
      Prospective studies of cohorts followed since birth show that pre-existing
      functional abnormalities can promote the appearance of bronchiolitis and
      bronchial obstruction syndrome. Asthma in infants comprises several phenotypes
      with very different prognoses.

PMID- 10941478
TI  - [Verotoxin-producing Escherichia coli infections: study of its prevalence in
      children in the Auvergne region].
AB  - Verotoxin producing Escherichia coli (VTEC) have been associated with disease
      outbreaks of diarrhea hemorrhagic colitis and hemolytic-uremic syndrome in
      humans. Contamination occurs mainly by ingestion of beef and dairy products, but
      water and person to person transmission have also been described. Most of the
      clinical signs are due to the production of Stx1 and/or Stx2 Shiga toxins, also
      called verotoxins. Other virulence factors include enterohemolysin, and the
      product of the eae gene, intimin, involved in the attaching and effacing
      adherence phenotype. The predominant serotype is O157:H7, but VTEC strains of
      more than one hundred serotypes can cause human disease. In order to determine
      the prevalence of VTEC infections among children in the central part of France,
      stool samples from hospitalized children were examined for stx1 and stx2 genes by
      using a polymerase chain reaction (PCR) technique. From October 1997 to September
      1998, 658 stool samples were analysed: among them 19 (3%) were stx-PCR positive.
      Only 8 children out of 19 had diarrhea, and for 5 of them, an enteric pathogen
      other than VTEC was isolated. VTEC strains were isolated from 10 samples: most of
      the isolates did not produce verotoxins at a high level, and they did not belong
      to serotypes associated with pathogenicity, which might explain the absence of
      relationship between VTEC isolation and pathogenicity in our study.

PMID- 10941479
TI  - [Pathology of Haemophilus infections: current situation in pediatrics].
AB  - Haemophilus influenzae is the main pathogen in community-acquired infections in
      children. Prior to the introduction of H. influenzae type b immunization (Hib),
      capsular type b H. influenzae was the most invasive type of H. influenzae, and
      was the major cause of meningitis in children in France and many developing
      countries. The introduction of a Hib vaccine program results in rapid and
      dramatic decline in the incidence of Hib infections in children. The resistance
      rate to beta-lactam antibiotics is slowly increasing with beta-lactamase
      production. Third generation cephalosporins are used for the treatment of
      invasive infection (meningitis etc.). The empiric treatment of otitis and
      respiratory tract infections in children is the combination of clavulanic acid
      and amoxicillin or third generation cephalosporins.

PMID- 10941480
TI  - [Intradermal tuberculin test].
AB  - Mantoux test expresses a delayed hypersensitivity induced after either BCG
      vaccination or a BK contact. In France, a purified protein fraction is used. The
      quality of technique and lecture are essential. The lowest positivity limit is >
      5 mm. Sensitivity and specificity are imperfect. For the interpretation of
      positivity, the most important factors are the age of vaccination (the younger
      the child is, the lower the reaction is) and the infection prevalence rate in the
      group considered (the lowest it is, the highest a criteria may be used for
      induration > 15 mm). The background is most important for interpretation. The
      main situations are a postvaccinal test, a diagnosis of infection (or illness) or
      the environment of a contagious adult. A lot of situations are less clear and
      require the knowing of a risk factor (risk people, contagion...). In spite of
      these limits, Mantoux test is the only valid technique, useful when considered
      with other points: collective (prevalence of the illness in some groups) or
      individual (contagion, clinical or radiological signs...).

PMID- 10941481
TI  - [Bacterial meningitis in infants 1 to 8 weeks old].
AB  - Bacterial meningitis in the newborn and infant remains a serious problem, with a
      mortality rate of 24% and a morbidity rate ranging from 30 to 50%. This
      retrospective study conducted between January 1982 and December 1997, aims to
      characterize the epidemiology of bacterial meningitis in infants less than 60
      days of age. Thirty-five infants between 6 and 60 days of age, hospitalized for
      bacterial meningitis in the pediatric units of Edouard-Herriot Hospital in Lyon,
      France, were included. The clinical presentation was not specific for most cases,
      hyperthermia being the most common symptom (97%). Neurological symptoms such as
      bulging fontanelle or nuchal rigidity were present in 30% and 8% of the cases,
      respectively. The four predominant meningeal pathogens were: group B
      streptococcus (36%), Escherichia coli (28%), meningogoccus (8.6%) and
      Staphylococcus aureus (8.6%). This study emphasizes the importance of prompt
      diagnosis, including CSF evaluation, and antimicrobial therapy in infants less
      than 2 months of age presenting an isolated fever.

PMID- 10941482
TI  - [Childhood visceral leishmaniasis in Provence].
AB  - Fifty-nine cases of children with visceral leishmaniasis were retrospectively
      studied in a survey of hospital records in the Provence region of South France
      concerning a 15 years period (1981 to 1997). None of the children was
      immunocompromised. The mean age was 31 months but 10 children were younger than
      one year. The male/female ratio was 0.73. Fever and splenomegaly were present in
      90% and 100% of the cases respectively. Anemia, leukopenia and thrombocytopenia
      were commonly observed. A medullogram was systematically performed, but direct
      microscopic examination of the bone marrow identified Leishmania in only 78% of
      the cases. In these patients, specific serology and genomic amplification using
      polymerase chain reaction were useful tools for the diagnosis. All patients were
      initially treated with meglumine antimonate (Glucantime). Twenty-six (44%)
      receiving the drug experienced at least one adverse event during treatment.
      Treatment failure occurred in 6 children (10%), who were subsequently cured with
      liposomal amphotericin B. Three additional children were treated with liposomal
      amphotericin B. All the children were finally cured and no death was observed.
      Pediatric visceral leishmaniasis is an uncommon disease in the endemic area of
      South France. Resistance to antimonial therapy occurs in children as well as in
      adults. Liposomal amphotericin B appears as an effective therapy for visceral
      leishmaniasis in children and could be used as a first-line treatment.

PMID- 10941483
TI  - [Marshall syndrome: results of a retrospective national survey].
AB  - Marshall's syndrome or periodic fever syndrome was first described in 1987 in the
      USA based on observations of 12 children under the age of five with periodic
      fever (> 38 degrees C) and accompanying aphtous stomatitis, pharyngitis, and
      cervical adenopathy (PFAPA). In 1998, a national retrospective study was carried
      out in France by the pediatric infectious pathology group, and a semeiological
      analysis was made of 22 cases. The main characteristics of Marshall's syndrome
      found in this patient population were in agreement with those reported in the
      literature. The onset of symptoms occurred between the age of 3 months and 12
      years, with a mean age of 5 years; no geographical or ethnic predisposing factors
      were noted. The diagnosis of symptoms was subsequently established at an age
      ranging from 5 months to 16 years, with a mean age of 6.5 years. It was
      determined that following an initial phase of generalized clinical manifestations
      (asthenia, cranial neuritis, dysphagia, anorexia), the symptoms become
      stereotyped, with the sudden appearance of high fever (> 40 degrees C),
      shivering, aphtous stomatitis, pharyngitis, and cervical adenopathy. Other
      symptoms such as cranial neuritis, arthralgia, and abdominal pain may also be
      present (50% of cases in the present study), but due to their variability of
      appearance they are of lesser diagnostic value. The main characteristic of
      Marshall's syndrome is its periodic aspect; with fever occurring every 6 to 9
      weeks, with a mean interval of 66 days before recurrence of fever compared to the
      shorter interval of 21 to 28 days reported in the literature. After excluding the
      presence of an infection, the differential diagnosis includes the following:
      familial Mediterranean fever, hyper IgD syndrome, and feverish neutropenia.
      During the periods of fever, an inflammatory syndrome with hyperleucocytosis and
      a marked increase in C-reactive protein (CRP) levels and sedimentation rate is
      observed. The most effective treatment seems to be the early administration of
      corticoids during the initial phase, prior to the appearance of more specific
      symptoms. The prognosis is excellent, with a progressive decrease in the
      incidence of periodic fever and an absence of complications. However, the
      etiology of Marshall's syndrome has not yet been determined.

PMID- 10941484
TI  - [Uro-nephropathies detected in utero. What strategy for postnatal survival?].

PMID- 10941485
TI  - [Perinatal administration of dexamethasone. What benefits in the premature
      infant].

PMID- 10941486
TI  - [Study of passive smoking measured by urinary cotinine in maternal and child
      protective health centers in North-Pas-de-Calais].
AB  - BACKGROUND: The aim of the study was to determine the circumstances of exposure
      to environmental tobacco smoke, to evaluate its importance by measurement of
      urinary cotinine, and to study the relationship with the children's medical
      history. POPULATION AND METHODS: It was a prospective investigation realized in
      20 outpatient pediatric clinics. The parents answered a questionnaire to assess
      the child's exposure as well as the child's medical and surgical history.
      Cotinine was measured in urine samples collected during the visit. Concentrations
      > 6 ng/mL were considered to be positive. RESULTS: Two hundred and one children
      were included in the study (mean age 17 months, extremes: 1-72 months), 107 of
      whom were exposed to environmental tobacco smoke. Urinary cotinine was found to
      be positive in 27 cases (13%). There was a positive relation between passive
      tobacco exposure and positive urinary cotinine (P < 0.001). Eighty of 201 mothers
      and 135 of 185 fathers smoked. There was a relation between positive urinary
      cotinine and the mother's smoking, as well as with a history of upper respiratory
      tract infection (rhinitis, otitis media) or adenoidectomy. No relation was found
      between a history of bronchiolitis and passive smoking. CONCLUSIONS: Passive
      tobacco exposure is very frequently encountered in our region. Urinary cotinine,
      which can be easily measured, might constitute an efficient tool in order to
      convince the parents of the reality of passive smoking.

PMID- 10941488
TI  - [Management of adolescents in pediatric hospitals. A national survey].
AB  - Hospital care of adolescents is a challenge for pediatric teams because of the
      characteristics and specific problems of this age group. METHODS: In 1996, a
      questionnaire was sent to all French public pediatric wards, 300 (i.e., 78%) of
      which participated. The goal of this survey was to investigate the facts and
      limitations encountered with hospitalization of patients 12 years and older.
      RESULTS: Data show that for more than half of the pediatric wards, the adolescent
      patient admission rate is higher than 10%. The upper age for hospitalization
      shows a shift towards adulthood, with 73% of the wards admitting adolescents up
      to 18 years of age. The main reasons for pediatric admission in this age group
      are somatic complaints, chronic diseases and suicide attempts. Psychosocial
      problems and psychiatric disorders are perceived as the most difficult to manage.
      However, a majority of pediatric wards appears to have an environment suitable
      for multidisciplinary networking. At the time of the survey, 39 wards (16%) had
      beds specifically destined for adolescents. These wards differed from others by
      their higher number of suicidal and anorexic inpatients. CONCLUSIONS: Our study
      shows that pediatric wards are in the avant-garde of adolescent hospital care and
      it brings new data on the various problems encountered in these patients. It
      stresses the special needs of pediatric teams today in the field of adolescent
      medicine and calls for the development of specific educational programs.

PMID- 10941487
TI  - [Mortality in a pediatric hospital. Six-year retrospective study].
AB  - AIMS: To define the characteristics of patients dying in a pediatric hospital,
      including causes and modes of death. PATIENTS AND METHODS: This retrospective,
      descriptive, epidemiologic study was performed between 1 January 1990 and 31
      December 1995. All patients who died in the hospital between these dates were
      included. Patients already dead on arrival (sudden infant death syndrome,
      children deceased during their transport), and those whose hospital records could
      not be found, were excluded. RESULTS: A total of 375 children were studied,
      including 195 neonates. The sex ratio was 1.3. Ninety-one percent of deaths took
      place in three departments: intensive care, neurosurgery-neurology and oncology.
      Median duration of hospitalization was three days. The most common causes of
      deaths were accidents, neurologic diseases (particularly among neonates) and
      tumours. Analysis of modes of death revealed that 41.1% occurred following
      unsuccessful resuscitation, 38.8% were the result of withdrawal of life-support
      or a 'do not resuscitate' order and 21.6% resulted from brain death. Evolution of
      modes of death over the six years showed a reduction of cases with unsuccessful
      resuscitation, an increase in decisions of 'do not resuscitate' orders and
      withdrawal of life-support and no change in rates of brain death. Organs were
      made available for transplantation from 12 of the 81 children with brain death
      (14.8%). CONCLUSION: Accidents were the most common cause of death. The
      distribution of deaths showed a clear increase in withdrawal or withholding of
      life-support care, relying on ethical decisions, which are more frequent than
      some years ago.

PMID- 10941489
TI  - [Lymphomas in children infected with HIV-1].
AB  - PURPOSE: To describe the features of lymphoma in human immunodeficiency virus
      (HIV)-infected children, their treatments and the outcome of patients. RESULTS:
      We analyzed seven HIV-infected children (four by mother-to-child transmission and
      three by transfusion) (25 months to 18.5 years old) with lymphoma (one Hodgkin's
      disease and six non-Hodgkin's lymphomas). All of them presented with a severe
      immunodepression and a high viral load. Five of six were high grade-B cell non
      Hodgkin's lymphoma of large-cell histologies (immunoblastic or centroblastic).
      Five were extranodular disease and three were metastatic at diagnosis. Epstein
      Barr virus was detected in four tumors. Five of seven received a multiagent
      chemotherapy. Toxicity was high. Treatment for the skin T lymphoma consisted of
      radiation therapy. Five children were complete responders (with survival three
      years, 2.5 years, 12, 18 and 18 months) and two died of progression of lymphoma
      (four and five months later). CONCLUSION: Incidence of lymphoma is increased in
      HIV-infected children. Anticancer chemotherapy regimens that include aggressive
      supportive care and concomitant antiretroviral therapy or immunotherapy may yield
      high survival rates.

PMID- 10941491
TI  - [Fallopian tube torsion in a 15-year-old adolescent].
AB  - Isolated Fallopian tube torsion in teenagers is extremely rare and diagnosis is
      difficult. Coelioscopy is necessary, but surgery often occurs too late for tube
      conservation. CASE REPORT: A case of Fallopian tube torsion bringing about a cyst
      is presented. Diagnostic difficulties, echography, treatment and cause are
      discussed. CONCLUSION: Early diagnosis and surgical intervention is mandatory
      when isolated Fallopian tube torsion is suspected.

PMID- 10941490
TI  - [Hemolytic anemia in a newborn after maternal treatment with nitrofurantoin at
      the end of pregnancy].
AB  - Drug administration during the last trimester of pregnancy may have adverse
      effects for the newborn. CASE REPORT: A hemolytic anemia occurred during the
      first hours of life in a full-term neonate whose mother had taken nitrofurantoin
      during the last month of pregnancy. CONCLUSION: The immature enzymatic systems of
      the neonate are exposed to this adverse effect and justify the recommendation not
      to prescribe nitrofurantoin at the end of pregnancy.

PMID- 10941492
TI  - [Epstein-Barr virus. An unusual cause of acute myocarditis in children].
AB  - Epstein-Barr virus does not belong to the principal causative agents of acute
      myocarditis, whose diagnosis and pathogenesis are often difficult to determine.
      Treatment is also controversial regarding the use of anti-inflammatory or
      immunosuppressive therapy. CASE REPORT: We describe a 13-month-old girl, admitted
      for acute heart failure, in whom cardiac catheterization with endomyocardial
      biopsy revealed an acute myocarditis. Acute viral titers indicated infectious
      mononucleosis caused by Epstein-Barr virus, and the virus genome was identified
      with a polymerase chain reaction in the patient's serum. The patient had clinical
      improvement after corticosteroid administration. CONCLUSION: The different
      diagnostic tools and the screening examinations to determine the causative agent
      of myocarditis are discussed. The frequency of Epstein-Barr virus in pathogenesis
      is also considered. The favorable outcome with immunosuppressive therapy suggests
      its administration in cases of acute myocarditis.

PMID- 10941493
TI  - [Perinatal thrombocytopenia of maternal origin].
AB  - Maternal causes of perinatal thrombocytopenia include neonatal alloimmune
      thrombocytopenia, autoimmune disorders, intrauterine infections and hypertensive
      diseases. The diagnosis of these pathologies is difficult because they can occur
      in sick neonates, but also in healthy babies without a history suggesting
      illness. The treatment has to be quickly established in order to decrease
      eventual hemorrhagic complications. These latter can be amplified by several
      clinical circumstances and especially by the platelet immaturity of this time of
      life. The risk of recurrence for the next pregnancies has to be determined and
      can lead to diagnostic or therapeutic measures during the antenatal period.

PMID- 10941494
TI  - [Radiologic case of the month. Myositis ossificans].

PMID- 10941495
TI  - [Menstrual cycle disorders in adolescents].
AB  - Long cycles and excessive uterine bleeding are the most common menstrual
      disorders in adolescents. Long cycles usually result from a benign transitory
      functional disorder which spontaneously resolves within two to three years after
      menarche; however, this diagnosis can only be retained in the absence of
      hirsutism or galactorrhea as revealing symptoms of functional ovarian
      hyperandrogenism, polycystic ovary syndrome, late form of congenital adrenal
      hyperplasia or hyperprolactinemia; ovarian failure will be considered in case of
      isolated long cycles persisting more than two years after menarche. Excessive
      uterine bleeding usually occurs early after menarche. Although the main cause is
      functional, resulting from anovulation and the related absence of progesterone,
      coagulation disorders must always be excluded. Management of these disorders are
      described.

PMID- 10941496
TI  - [The double system of child protection: a French original].
AB  - France has a double system of child welfare as decreed by the law of July 1989.
      Social welfare is under the responsibility of the Regional Council (social
      services, early childhood health services, and child protection services). These
      type of services require the family's collaboration with respect to the proposals
      concerning child protection: financial aid, family counseling, and placement. In
      case of severe danger, or if it is impossible to obtain the family's
      collaboration, the child's judge can order family counseling or placement. None
      of these measures modifies parental authority. A child in danger and the child's
      best interest are the two fundamental concepts which ought to guide social
      welfare and children's court workers in choosing the best possible protection
      measure.

PMID- 10941497
TI  - [Hand infections in children].
AB  - Subcuticular whitlow is the most frequent form of hand infections in children,
      mainly resulting from the penetration of a foreign body such as a thorn bush or
      onychophagy. Local antispesis, Dakin's fluid baths and eventually antibiotics
      directed toward Staphylococcus aureus are usually effective therapies. Extension
      to a subcutaneous whitflow needs surgery. Specific treatment must be used in case
      of fungal and herpetic whitlows. Paronychia tendinosa is a severe form of
      infection affecting flexor tendons sheaths with a high risk of sequelae; it
      requires an emergency surgical excision and i.v. anti-Staphylococcus aureus
      antibiotics therapy. Hand bites need particular attention and systematic surgical
      advice.

PMID- 10941498
TI  - [Knowledge and traditional practice of mothers about neonatal care].

PMID- 10941508
TI  - An improved nonfluorescent detection system for in situ hybridization in plants.
AB  - Molecular cytogenetics, particularly the localization of DNA sequences by in situ
      hybridization, has increased our understanding about the genomic structure of
      plants and animals. We demonstrate here the application of an improved
      nonfluorescent in situ hybridization system detection (DAKO GenPoint system) to
      plant chromosomes. Using this system, highly repetitive 18S-25S rRNA genes were
      mapped on Vicia faba chromosomes (2n = 12). The modified method of this
      horseradish peroxidase based enzymatic detection system gave satisfactory results
      that are comparable to fluorescent signal detection.

PMID- 10941509
TI  - A review of fluorescence in situ hybridization (FISH): current status and future
      prospects.
AB  - Fluorescence in situ hybridization (FISH) is a powerful technique for detecting
      DNA or RNA sequences in cells, tissues and tumors. This molecular cytogenetic
      technique enables the localization of specific DNA sequences within interphase
      chromatin and metaphase chromosomes and the identification of both structural and
      numerical chromosome changes. FISH is quickly becoming one of the most
      extensively used cytochemical staining techniques owing to its sensitivity and
      versatility, and with the improvement of current technology and cost
      effectiveness, its use will surely continue to expand. Here we review the wide
      variety of current applications and future prospects of FISH technology.

PMID- 10941510
TI  - Detection of mineralized structures in early stages of development of marine
      Teleostei using a modified alcian blue-alizarin red double staining technique for
      bone and cartilage.
AB  - We have developed a procedure for staining cartilage and bone in fish larvae as
      small as 2 mm (notochord length), for which standard alcian blue/alizarin red
      procedures did not give positive and/or consistent results. Small calcified
      structures only 100-200 microns in length can be clearly visualized. The method
      is suitable for both ontogenic studies during early stages of skeletal
      development in most marine fishes (e.g., Sparus aurata L., Solea senegalensis
      Kaup), whose larvae at hatching are often only a few millimeters long and for
      detecting skeletal abnormalities in small larvae. This procedure can also be used
      for specimens that have been preserved in 100% ethanol for up to two years.

PMID- 10941511
TI  - Localization of protease-activated receptors-1 and -2 in human mast cells:
      indications for an amplified mast cell degranulation cascade.
AB  - Protease-activated receptors (PARs) belong to a family of G-coupled seven
      transmembrane receptors that are activated by a proteolytic cleavage of their N
      termini. Recent studies suggest the involvement of protease-activated receptors-1
      and -2 (PAR-1, PAR-2) activators in mast cell degranulation in various
      physiological and pathophysiological processes in inflammatory responses.
      Although PAR-1 and PAR-2 activating proteases, thrombin and tryptase, have been
      associated with mast cell activation, PAR-1 and PAR-2 have not been localized
      within these cells. We describe here the localization of PAR-1 and PAR-2 in mast
      cells from various normal human tissues using immunohistochemical and double
      immunofluorescence techniques. The presence of these receptors on the membrane
      may explain the actions of accessible extracellular thrombin and tryptase for
      mast cell activation. In addition to the membrane labeling, these receptors are
      also localized on the membrane of the intracellular tryptase-positive granules,
      which may function to sustain further mast cell degranulation upon exocytosis.
      The localization of these two receptors in mast cells suggests a novel mechanism
      for controlling mast cell activation through regulation of PAR-1 and PAR-2.

PMID- 10941512
TI  - In situ detection of a PCR-synthesized human pancentromeric DNA hybridization
      probe by color pigment immunostaining: application for dicentric assay
      automation.
AB  - We report a low cost and efficient method for synthesizing a human pancentromeric
      DNA probe by the polymerase chain reaction (PRC) and an optimized protocol for in
      situ detection using color pigment immunostaining. The DNA template used in the
      PCR was a 2.4 kb insert containing human alphoid repeated sequences of
      pancentromeric DNA subcloned into pUC9 (Miller et al. 1988) and the primers
      hybridized to internal sequences of the 172 bp consensus tandem repeat associated
      with human centromeres. PCR was performed in the presence of biotin-11-dUTP, and
      the product was used for in situ hybridization to detect the pancentromeric
      region of human chromosomes in metaphase spreads. Detection of pancentromeric
      probe was achieved by immunoenzymatic color pigment painting to yield a permanent
      image detected at high resolution by bright field microscopy. The ability to
      synthesize the centromeric probe rapidly and to detect it with color pigment
      immunostaining will lead to enhanced identification and eventually to automation
      of various chromosome aberration assays.

PMID- 10941513
TI  - HPLC analyses of cultures of Phoma spp.: differentiation among groups and species
      through secondary metabolite profiles.
AB  - The metabolite profiles of 26 isolates of the blackleg fungus (Leptosphaeria
      maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode ex Fr.)
      Desm.), obtained from diverse parts of the world (part of the International
      Blackleg Crucifer Network collection), were studied utilizing specific culture
      conditions, HPLC analysis, and a set of chemical markers. This fungus is the
      causative agent of blackleg disease of brassica oilseeds; a virulent strain of
      the pathogen has caused significant rapeseed (Brassica napus L., and B. rapa L.)
      and canola (B. napus L., and B. rapa L.) losses in Canada, and is also considered
      a serious agricultural problem worldwide. Effective surveys of blackleg epidemics
      require simple and reliable analytical methodology to differentiate among the
      diverse groups of isolates. The chemical analysis of phytotoxins and related
      secondary metabolites is perhaps one of the most discriminating and the least
      ambiguous methods for differentiation of Phoma blackleg isolates. Following HPLC
      analyses, the 26 isolates could be placed in three main groups, irrespective of
      country of origin: isolates producing phomamide and sirodesmins, isolates
      producing indolyl dioxopiperazines, and isolates producing polyketides.
      Discussion of the implications of our findings and suggestions for species
      reclassification are provided.

PMID- 10941514
TI  - Effects of the Fusarium spp. mycotoxins fusaric acid and deoxynivalenol on the
      growth of Ruminococcus albus and Methanobrevibacter ruminantium.
AB  - The Fusarium spp. mycotoxins fusaric acid and deoxynivalenol (DON) were tested
      for antimicrobial activity against Ruminococcus albus and Methanobrevibacter
      ruminantium. The growth of both organisms was inhibited by fusaric acid as low as
      15 micrograms/mL (84 microM) but not by DON, at levels as high as 100
      micrograms/mL (338 microM). No synergistic inhibitory effect was observed with
      DON plus fusaric acid. Neither organism was able to adapt to the fusaric acid and
      responses of each organism to the compound were different. The optical density
      (OD) maximum for R. albus, but not for M. ruminantium, was diminished after 28
      days incubation at concentrations of fusaric acid below 240 micrograms/mL.
      Inhibition of R. albus started before significant growth had occurred, while M.
      ruminantium doubled twice before the onset of inhibition. Responses to picolinic
      acid, an analog of fusaric acid, were also dramatically different between the two
      microorganisms with M. ruminantium exhibiting a severe lag followed by a complete
      recovery of growth, while R. albus was only slightly inhibited with no lag. These
      results suggest that the mechanism of fusaric acid inhibition is specific to each
      microorganism. This is the first demonstration of the common mycotoxin fusaric
      acid inhibiting the growth of rumen bacteria.

PMID- 10941515
TI  - Recovery and viability of Cryptosporidium parvum oocysts and Giardia intestinalis
      cysts using the membrane dissolution procedure.
AB  - Previously, the cellulose acetate membrane filter dissolution method was reported
      to yield Cryptosporidium parvum oocyst recoveries of 70.5%, with recovered
      oocysts retaining their infectivity. In contrast, high spike doses (approximately
      1 x 10(5) Cryptosporidium parvum oocysts and Giardia intestinalis cysts) yielded
      recoveries ranging from 0.4% to 83.9%, and 3.2% to 90.3%, respectively, in this
      study. Recoveries with low spike doses (approximately 100 (oo)cysts) continued to
      demonstrate high variability also. Efforts to optimize the method included
      increased centrifugation speeds, suspension of the final concentrate in deionized
      water for organism detection on well slides, and analysis of the entire
      concentrate. A comparison of two monoclonal antibodies was also conducted to
      identify potential differences between antibodies in detection of organisms.
      Archived source and finished water samples were spiked, yielding variable
      recoveries of C. parvum oocysts (11.8% to 71.4%) and G. intestinalis cysts (7.4%
      to 42.3%). Effects of organic solvents used in the membrane dissolution procedure
      on the viability of recovered (oo)cysts was determined using a fluorogenic vital
      dyes assay in conjunction with (oo)cyst morphology, which indicated > 99%
      inactivation. These data indicate that the membrane dissolution procedure yields
      poor and highly variable (oo)cyst recoveries, and also renders the majority of
      recovered organisms non-viable.

PMID- 10941516
TI  - Selective isolation and distribution of Actinobispora strains in soil.
AB  - A simplified enrichment method for selective isolation of Actinobispora strains
      from soil is described. Actinobispora spores were tolerant to dry-heat treatment
      at 110 degrees C for 15 min. Actinobispora was more resistant to 1 microgram/mL
      leucomycin, 1 microgram/mL novobiocin, and 0.5 microgram/mL tunicamycin than
      Streptomyces dominant in soil, which prevents selective isolation of
      Actinobispora. Percentages of Actinobispora colonies on the isolation plate were
      increased by addition of antibiotics and dry-heat treatment of the soil samples.
      By combining the techniques described above, this genus was isolated from 105 out
      of 574 soil samples (18% of the samples tested). It was recovered from the soil
      samples with pH values ranging 5.0 to 8.9, and 78% of strains were isolated from
      neutral soil (pH 6.0-8.0). A number of Actinobispora strains were isolated from
      various soils around the world. Actinobispora strains are widely distributed in
      the world at relatively high frequency.

PMID- 10941517
TI  - Role of the outer membrane in the accumulation of quinolones by Serratia
      marcescens.
AB  - Accumulation of four quinolones by Serratia marcescens was measured
      fluorometrically. The passage of quinolones through the outer membrane was
      studied in both lipopolysaccharide-deficient and porin-deficient mutants. The
      lipopolysaccharide (LPS) layer formed a partially effective barrier for highly
      hydrophobic quinolones such as nalidixic acid. Quinolones with a low relative
      hydrophobicity coefficient seemed to pass preferentially through the water-filled
      Omp3 porin channels. Results were confirmed when Omp3 was cloned in a porin
      defective Escherichia coli.

PMID- 10941518
TI  - Evaluation of polyclonal-antibody-based immunoassays for detection of Sclerotinia
      sclerotiorum on canola petals, and prediction of stem rot.
AB  - The potential for using polyclonal-antibody-based immunoassays for detection of
      Sclerotinia sclerotiorum on canola petals as part of a disease prediction model
      was investigated. A commercial ELISA kit designed for Sclerotinia homoeocarpa was
      evaluated for specificity to S. sclerotiorum in comparison to other Sclerotinia
      spp., and known phyllosphere fungi. This polyclonal-antibody-based kit cross
      reacted with antigens from other Sclerotinia spp., and fungi, and absorbance
      values obtained from S. sclerotiorum-infested canola petals were poorly
      correlated with percentages of infested petals as determined by plating on semi
      selective medium, except when petals were incubated at high humidity for 24 h at
      20 degrees C-22 degrees C prior to ELISA evaluation. Additional polyclonal
      antibodies were prepared from mycelial and semi-purified cell wall antigens, and
      these antibodies were more specific to S. sclerotiorum than the ELISA kit.
      However, absorbance values obtained from S. sclerotiorum-infested canola petals
      were poorly correlated with percentages of infested petals as determined by
      plating on semi-selective medium. The results are discussed in relation to the
      use of polyclonal-antibody-based immunoassays for the prediction of epidemics or
      crop risk from sclerotinia stem rot of canola.

PMID- 10941519
TI  - Effect of delivery method and population size of Trichoderma harzianum on growth
      response of unrooted chrysanthemum cuttings.
AB  - In a previous study, addition of Trichoderma harzianum Rifai isolate T-12 to a
      propagative medium resulted in improved performance of chrysanthemum cuttings.
      However, root and shoot growth of one cultivar, 'Dark Bronze Charm', were more
      responsive to a lower (5 g T-12/kg medium) than higher (25 g T-12/kg medium) rate
      of fungal propagules, suggesting potential phytotoxicity at higher
      concentrations. The objectives of this study were to investigate higher rates of
      T-12 medium amendment for phytotoxicity, and to examine an alternative method of
      delivering the fungus to the propagative medium in order to obtain a more uniform
      response from cuttings. Isolate T-12 was added to the propagative medium as
      either a powdered peat-bran amendment (0, 5, or 50 g T-12/kg medium) or as
      alginate prills (80 or 800 g T-12/kg medium). There were no differences among
      treatments on day seven, but by day 21, shoot fresh weight and heights were
      significantly greater for plants treated with prills at 800 g T-12/kg medium.
      Both prill treatments resulted in greater shoot height on day 14 and 21 than all
      other treatments, which were similar to controls. Amendment with T-12 powder at
      50 g/kg increased root length, but 80 g/kg medium added as prills decreased root
      dry weight compared to the control. The highest rate of T-12 (800 g prills/kg
      medium) had no effect on root growth. This suggests that moderate, rather than
      high rates of T-12 are more effective in promoting rooting of unrooted
      chrysanthemum, and that there is a potential for phytotoxic effects on root
      growth with higher rates.

PMID- 10941520
TI  - Identification and characterization of nuclease activities in anaerobic
      environmental samples.
AB  - DNA-degrading activity from anaerobic samples of bovine ruminal fluid, primary
      anaerobic digestor wastewater, freshwater sediments, and marine sediments was
      observed in the presence of 5 mM EDTA. Nuclease activity experiments involved
      exposing salmon chromosomal DNA to the environmental samples in 50 mM pH 7.2
      buffer, incubating at 37 degrees C, and subjecting the products to
      electrophoresis. The same stock and concentration of EDTA used in these assays (5
      mM) completely inhibited commercial grade DNase. Nuclease activity in two of the
      samples, ruminal fluid and wastewater, was further characterized. DNA degradation
      in the ruminal sample was significantly reduced when EDTA or citrate
      concentrations were increased to 50 mM or above. DNA degradation activity in
      ruminal fluid was associated with material that passed through a 0.22-micron
      filter, but wastewater activity was associated with material retained by a 3
      micron filter. Degradation activity in the wastewater was resistant to heat
      pretreatment, whereas the rumen activity was heat-labile (70 degrees C, 60 min).
      These results demonstrated the biochemical complexity of these two environments
      and that high molecular weight DNA has a short half-life in these anaerobic
      environments.

PMID- 10941521
TI  - Inoculation of somatic embryos of sweet potato with an arbuscular mycorrhizal
      fungus improves embryo survival and plantlet formation.
AB  - Responses of somatic embryos of sweet potato (Ipomoea batata (L.) Poir., cv.
      White Star) at different developmental stages to in vitro inoculation with Glomus
      etunicatum (Becker and Gerdemann) (isolate INVAM FL329) were evaluated. Somatic
      embryos were grown in glass tubes containing sterilized vermiculite and sand. A
      layer of natrosol plus White's medium was used as a carrier for arbuscular
      mycorrhizal (AM) fungal spores. Survival of embryos inoculated with AM fungi was
      significantly (P < 0.05) greater than that of noninoculated embryos at the rooted
      cotyledonary-torpedo and rooted-elongated-torpedo developmental stages.
      Mycorrhizae significantly (P < 0.05) increased plantlet formation only when
      inoculation occurred at the rooted-elongated-torpedo developmental stage. The
      growth stage at which the embryos were inserted into the glass tubes exerted a
      significant influence upon plantlet formation, and plantlet formation was further
      enhanced by inoculation with G. etunicatum. Plantlet formation was greatest at
      the rooted-elongated-torpedo stage. These results demonstrate that inoculation of
      somatic embryos with AM fungi improves embryo survival and plantlet formation,
      and could enhance use of somatic embryos as synthetic seeds.

PMID- 10941522
TI  - The importance of recA mutant strains for the study of antifungal genes in
      Pseudomonas aureofaciens PA147-2.
AB  - Pseudomonas aureofaciens PA147-2 shows antifungal activity toward a variety of
      plant pathogenic fungi. We have been investigating the molecular mechanisms
      underlying the fungal inhibition, and during these studies it was observed that
      the use of pLAFR3-based cosmids for in trans complementation of mutants lacking
      antifungal activity is hindered by cosmid instability. It was hypothesised that
      the cosmid stability could be improved by inactivation of recA. The recA gene of
      PA147-2 was cloned and shown to complement recA mutants of E. coli, restoring
      RecA-dependent functions when expressed in trans. Two recA mutants of PA147-2
      were constructed. Both of these mutants show sensitivity to DNA damage. Cosmid
      pPS2122 restores antifungal activity to a mutant by allele exchange, but is
      unstable in trans. The stability of pPS2122 is shown to be improved in a recA
      mutant of PA147-2 with respect to the wild type.

PMID- 10941523
TI  - Substrate-dependent differential expression of Humicola grisea var. thermoidea
      cellobiohydrolase genes.
AB  - Transcription of fungal cellulase genes may be affected by substrate induction.
      We studied the expression of Humicola grisea var. thermoidea cellobiohydrolase
      genes (cbh1.1 and cbh1.2) under induction by several soluble and insoluble carbon
      sources. Using the RT-PCR technique, the cbh1.2 transcript was detected in all
      the conditions assayed along the growth curve. Catabolite repression, which
      frequently occurs in other fungal celluloytic systems, was not observed. On the
      other hand, cbh1.1 transcription was shown to be driven by insoluble and complex
      lignocellulosic substrates. In summary, the cbh1.2 gene product is constitutively
      produced, while cbh1.1 seems to respond to a distinct regulatory mechanism.

PMID- 10941524
TI  - Streptomyces halstedii K122 produces the antifungal compounds bafilomycin B1 and
      C1.
AB  - Streptomyces halstedii K122 was previously found to produce antifungal compounds
      on solid substrates that inhibit radial growth of fungi among Ascomycetes,
      Basidiomycetes, Deuteromycetes, Oomycetes, and Zygomycetes, and strongly affected
      hyphal branching and morphology. During growth of S. halstedii K122 in submerged
      culture, no antifungal activity could be detected. However, cultivation of S.
      halstedii in thin (1 mm) liquid substrate layers in large surface-area tissue
      culture flasks caused intense growth and sporulation of S. halstedii K122, and
      the biologically active compounds could be extracted from the mycelium with
      methanol. Antifungal compounds were purified using C18 solid phase extraction and
      silica gel column chromatography, and identified as bafilomycins B1 and C1, using
      2D NMR and FAB MS. Production of bafilomycins, which are specific inhibitors of
      vacuolar ATPases, has not been reported from S. halstedii previously. Minimum
      inhibitory concentrations (MIC) of bafilomycins B1 and C1, amphotericin B, and
      nikkomycin Z were determined at pH 5.5 and 7.0 for the target fungi Aspergillus
      fumigatus, Mucor hiemalis, Penicillium roqueforti, and Paecilomyces variotii.
      Penicillium roqueforti was the most sensitive species to all the compounds
      investigated. The MIC values for amphotericin B were 0.5-4 micrograms.mL-1 for
      the fungi tested, and pH did not affect the toxicity. The MIC values for
      nikkomycin Z ranged from < 0.5 microgram.mL-1 for Mucor hiemalis to > 500
      micrograms.mL-1 for Aspergillus fumigatus, and pH had no influence on toxicity.
      Bafilomycins B1 and C1 were equally active against the fungal species tested,
      with MIC values in the range of < 0.5-64 micrograms.mL-1. All fungi were more
      sensitive to both bafilomycin B1 and C1 at pH 7.0 than at pH 5.5.

PMID- 10941526
TI  - Molecular cloning, heterologous expression, and functional characterisation of a
      malate synthase gene from Streptomyces coelicolor A3(2).
AB  - With the rapid generation of genetic information from the Streptomyces coelicolor
      genome project, deciphering the relevant gene products is critical for
      understanding the genetics of this model streptomycete. A putative malate
      synthase gene (aceB) from S. coelicolor A3(2) was identified by homology-based
      analysis, cloned by polymerase chain reaction, and fully sequenced on both
      strands. The putative malate synthase from S. coelicolor has an amino acid
      identity of 77% with the malate synthase of S. clavuligerus, and possesses an
      open reading frame which codes for a protein of 540 amino acids. In order to
      establish the identity of this gene, the putative aceB clones were subcloned into
      the expression vector pET24a, and heterologously expressed in Escherichia coli
      BL21(DE3). Soluble cell-free extracts containing the recombinant putative malate
      synthase exhibited a specific activity of 1623 (nmol.mg-1.min-1), which is an
      increment of 92-fold compared to the non-recombinant control. Thus, the gene
      product was confirmed to be a malate synthase. Interestingly, the specific
      activity of S. coelicolor malate synthase was found to be almost 8-fold higher
      than the specific activity of S. clavuligerus malate synthase under similar
      expression conditions. Furthermore, the genomic organisation of the three
      Streptomyces aceB genes cloned thus far is different from that of other bacterial
      malate synthases, and warrants further investigation.

PMID- 10941525
TI  - Isolation of a new laccase isoform from the white-rot fungi Pycnoporus
      cinnabarinus strain ss3.
AB  - Two extracellular laccase isoforms (Lac I and Lac II) produced by the white-rot
      fungus Pycnoporus cinnabarinus from the monokaryotic strain ss3 were purified
      from ferulic-acid-induced liquid culture medium using ammonium sulphate
      precipitation, followed by anion-exchange chromatography on a Mono Q column.
      Strain ss3 is the first generation of the parental strain P. cinnabarinus I-937.
      The new isolated isoform, Lac II, consists of an 86,000 molecular weight protein
      as determined by SDS polyacrylamide gel electrophoresis. The N-terminal amino
      acid sequences of both isoforms were determined, and compared to known laccase
      protein sequences of other organisms.

PMID- 10941527
TI  - Clay minerals protect bacteriophage PBS1 of Bacillus subtilis against
      inactivation and loss of transducing ability by UV radiation.
AB  - The effect of UV radiation on the survival of and transduction by phage PBS1 of
      Bacillus subtilis, free or adsorbed on the clay minerals montmorillonite (M) and
      kaolinite (K), was studied. After free or clay-associated phage (approximately
      10(7) PFU.mL-1) was irradiated with UV light (254 nm) for 0, 1, 2, 5, 10, and 30
      min and then allowed to infect B. subtilis FB300 (thiB4 metA29 argF4 Rfmr), the
      phage was titered, and Met+ transductants were enumerated on selective media.
      After 1 min of irradiation, the titer of free and clay-associated phage decreased
      significantly (approximately 1.6 times for free phage, and approximately 4.9 and
      6.8 times for M and K, respectively), whereas the transduction frequency
      increased significantly (approximately 3 times for free phage and approximately
      1.4 and 2.2 times for M and K, respectively). The titer and transduction
      frequency of clay-associated phage remain essentially constant between 1 and 10
      min of irradiation, whereas the titer of free phage decreased by approximately 1
      order of magnitude after 5 min of irradiation. When free phage was irradiated for
      10 min, the titer and transduction frequency decreased by approximately 2 and 0.5
      orders of magnitude, respectively, whereas 30 min of irradiation was necessary to
      obtain comparable decreases with clay-associated phage. These results indicated
      that phages are protected to some extent from UV radiation when adsorbed on clay
      minerals.

PMID- 10941528
TI  - Long-lived alpha emitters in radioimmunotherapy: the mischievous progeny.

PMID- 10941529
TI  - Controversies in sentinel lymph node biopsy for breast cancer.
AB  - Sentinel lymph node biopsy, validated in melanoma staging, is currently under
      investigation for breast cancer staging. Reports suggest that the sentinel lymph
      node has a high predictive value in determining the presence of axillary
      metastases. Identification of a sentinel lymph node that is free of metastatic
      tumor cells may eliminate the necessity of performing a standard axillary lymph
      node dissection with its attendant morbidity. Numerous techniques are utilized to
      identify the sentinel node with approximately the same success rate. This paper
      will address some of the controversial areas of sentinel lymph node biopsy and
      offer an option for physicians who want to develop a sentinel lymph node program
      in their hospital.

PMID- 10941530
TI  - Evaluation of 225Ac for vascular targeted radioimmunotherapy of lung tumors.
AB  - Several alpha particle emitting radioisotopes have been studied for use in
      radioimmunotherapy. Ac-225 has the potential advantages of a relatively long half
      life of 10 days, and a yield of 4 alpha emissions in its decay chain with a total
      energy release of approximately 28 MeV. A new, 12 coordination site chelating
      ligand, HEHA, has been chemically modified for coupling to targeting proteins
      without loss of chelating ability. HEHA was coupled with MAb 201B which binds to
      thrombomodulin and accumulates efficiently in murine lung. Ac-225 was bound to
      the HEHA-MAb 201B conjugate and injected into BALB/c mice bearing lung tumor
      colonies of EMT-6 mammary carcinoma. Biodistribution data at 1 and 4 h
      postinjection indicated that, as expected, 225Ac was delivered to lung
      efficiently (> 300% ID/g). The 225Ac was slowly released from the lung with an
      initial t1/2 = 49 h, and the released 225Ac accumulated in the liver. Injection
      of free HEHA was only partially successful in scavenging free 225Ac. In addition
      to the slow release of 225Ac from the chelate, data indicated that decay
      daughters of 225Ac were also released from the lung. Immediately after organ
      harvest, the level of 213Bi, the third alpha-decay daughter, was found to be
      deficient in the lungs and to be in excess in the kidney, relative to equilibrium
      values. Injected doses of 225Ac MAb 201B of 1.0 microCi, delivering a minimum
      calculated absorbed dose of about 6 Gy to the lungs, was effective in killing
      lung tumors, but also proved acutely radiotoxic. Animals treated with 1.0 microCi
      or more of the 225Ac radioconjugate died of a wasting syndrome within days with a
      dose dependent relationship. We conclude that the potential for 225Ac as a
      radioimmunotherapeutic agent is compromised not only by the slow release of 225Ac
      from the HEHA chelator, but most importantly by the radiotoxicity associated with
      decay daughter radioisotopes released from the target organ.

PMID- 10941531
TI  - Mapping sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue
      dye, and intraoperative gamma-probe.
AB  - The purpose of the present work was two-fold: 1) to evaluate the predictive value
      of the sentinel lymph node (sLN) versus the axillary-node status in patients with
      T1-T2 breast cancer, and 2) to form an experimental basis for a randomized trial
      in which one group of patients with non-metastatic sLN will not have axillary
      dissection. Of a group of 284 patients considered for this analysis, 264 had a T1
      cancer (16 T1a, 37 T1b and 211 T1c), while 20 had a T2 cancer; 243 patients were
      in clinical stage N0 and 41 were N1. All patients underwent lymphoscintigraphy 18
      hr before surgery: 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids
      (particle size between 50-80 nm) was injected subdermally at the cutaneous
      projection of the tumor. Static gamma-camera images were acquired every 10-15
      minutes until scintigraphic identification of the sLN. At surgery, 1-2 mL of
      Patent-Blue Violet was injected subdermally, and the sLN was searched by gamma
      probe and by the dye method. The surgically isolated sLN was processed for
      intraoperative Hematoxylin & Eosin (H&E) histology, then for delayed histological
      and immunohistochemical examinations. The sLN was successfully identified by the
      combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases
      (97.9%). The Patent-Blue dye technique alone identified fewer sLNs than the
      radioisotopic procedure alone (56.3% versus 97.2%). Analysis of the predictive
      value of the sLN as to the status of axillary lymph nodes was limited to 197
      patients undergoing standard axillary dissection irrespective of the sLN status.
      Overall, 63/191 (33%) identified sLNs were metastatic, the sLN alone being
      involved in 37/63 (58.7%) patients; a positive axilla status with negative sLN
      was found in 10/73 patients with metastatic involvement (13.7% false-negative
      rate). In conclusion, subdermal lymphoscintigraphy was confirmed to be an
      effective technique for sLN mapping; the addition of Patent-Blue dye minimally
      improved intra-surgical identification of the sLN. There was a high, but not
      absolute, correlation between a negative sLN and a negative axilla.

PMID- 10941532
TI  - Neutron activation of NDDP, a liposomal platinum antitumor agent.
AB  - Cis-bis-neodecanoato-trans-R,R-1,2-diamminocyclohexane platinum (II) [NDDP] is a
      liposome-entrapped platinum compound currently, in phase II clinical trials, that
      has been shown to undergo intraliposomal activation. The objective of this study
      was to determine the feasibility of activating NDDP and using the induced
      radioactivity to monitor NDDP distribution and penetration. METHODS: Neutron
      activation analysis (NAA) was done on NDDP using the nuclear reactor at Texas A &
      M University, College Station, Texas. After a 3-hour irradiation, the NDDP
      samples were analyzed using an HPGE (high purity germanium) detector to determine
      the activation of the radioisotopic platinum. This was followed by HPLC-UV
      analysis to determine the stability of NDDP after exposure to the reactor's core.
      RESULTS: Platinum radioisotopes were produced along with potassium-40 and sodium
      24. Irradiation did not result in any significant degradation of NDDP.
      CONCLUSIONS: (1) Irradiating fully synthesized NDDP is feasible for diagnostic
      use if a purification step is taken after the irradiation, and (2) radiation
      exposure is lessened by irradiating NDDP after synthesis rather than starting
      with high-specific-activity isotopes.

PMID- 10941533
TI  - Rhenium-188-HEDP in the palliative treatment of bone metastases.
AB  - INTRODUCTION: Rhenium-188-HEDP (188Re-HEDP) is a new and attractive
      radiopharmaceutical for the treatment of bone pain due to metastases. As a
      product of a 188W/188Re generator it is convenient for clinical use. With a short
      physical half life of 16.9 hours and a maximal beta-energy of 2.1 MeV, it is
      suitable for therapy. METHODS: We investigated the influence of 188Re-HEDP on
      pain relief, analgesic intake and impairment of bone marrow function in 15
      patients. All patients were interviewed using standardized questions before, and
      1, 2, 3, 4, 8, and 12 weeks after therapy. Blood samples were drawn weekly for 12
      weeks, and a blood count was performed. Patients underwent gamma camera imaging
      to determine the radionuclide accumulation 4, 20, and 28 hours after therapy. The
      patients were treated with 1600 to 3459 MBq of 188Re-HEDP. RESULTS: Patients
      showed an improvement of the Karnofsky performance index from 74 +/- 8% to 84 +/-
      11% 12 weeks after therapy. This improvement was statistically significant (p =
      0.001). Eighty percent of the patients described pain relief and reduction of
      analgesics. Twenty percent of the patients could discontinue their analgesics.
      Mean platelet count decreased from (284 +/- 84)*10(3)/microliter to (205 +/-
      62)*10(3)/microliter, and mean leukocyte count from (7.5 +/-
      1.5)*10(3)/microliter to (5.9 +/- 2.1)*10(3)/microliter after therapy. The
      maximal differences between the values of platelets and leukocytes before and
      after therapy were not statistically significant (p = 0.021 and p = 0.094).
      Prostate specific antigen decreased from 95 +/- 83 ng/ml to 41 +/- 21 ng/ml, the
      difference was not statistically significant (p = 0.443). The bone accumulation
      4, 20, and 28 hours after therapy was 1.3 +/- 0.5%, 0.6 +/- 0.3%, and 0.45 +/-
      0.2% of the injected dose of a single metastasis, and 57 +/- 17%, 15.5 +/- 2% and
      11 +/- 3% in the whole body, respectively. The effective half-life of 188Re-HEDP
      was 15.3 +/- 3.0 hours in the bone metastases, and 11.4 +/- 2.8 hours in the
      whole body. This corresponds to a residence time of 0.22 +/- 0.25 hours in the
      bone metastases, and of 10.54 +/- 2.59 hours in the whole body. CONCLUSION: In a
      small patient population, 188Re-HEDP therapy for bone pain palliation was
      effective and was associated with minimal toxicity.

PMID- 10941534
TI  - The TH1 and TH2 cytokine network in healthy subjects: suggestions for
      experimental studies to create prognostic and diagnostic indices for
      biotherapeutic treatments.
AB  - In vivo and in vitro studies have demonstrated the selective regulatory effect
      that TH1 and TH2 cytokines reciprocally exert in the regulation of the
      polarization of precursor cells into TH1 or TH2 types. The study of the network
      relationships between TH1 and TH2 (TH1/TH2) cytokines in healthy subjects could
      lead to a better understanding of how the physiological network of cytokines
      regulates the immune response. Such study could lead to gain suggestions for
      follow-up experiments to create prognostic and diagnostic indices for
      biotherapeutic treatments of patients. Hence we determined serum levels
      (environment network) and PBMC production (cellular network) of IL2, IFN gamma,
      IL4, IL6 and IL10 in the peripheral blood of healthy subjects; these cytokines
      made up our networks under basic conditions. Both men and women were studied as
      hormones can influence the polarization of TH1 and TH2 cells. Cytokines within
      the physiological network function simultaneously so multivariate statistical
      methods were used to study TH1/TH2 relationships. The use of mathematical
      modelling is the only effective way of studying the immune system as a whole. The
      physiological TH1/TH2 network under activation conditions was evaluated by
      incorporating: sIL2R and sIL6R into the basic environment network model and the
      production levels of cytokines by PBMC after PHA stimulus, into the basic
      cellular network model. The influence of APC was evaluated by adding: serum
      levels of TNF alpha and IL1 beta to the environment network model, and production
      levels of IFN gamma, IL10 and IL6, after stimulus with LPS, to the cellular
      network model. Our results led us to hypothesize that the physiological network
      of TH1/TH2 cytokines regulates TH polarization by means of specific relationships
      between TH1 and TH2 cytokines, which may be different in men and women. These
      relationships could be studied experimentally to create prognostic and diagnostic
      indices for more efficient prevention programs and biotherapeutic treatments of
      patients.

PMID- 10941535
TI  - Mitogenic activity of gelatin to murine spleen cells.
AB  - We reported previously that gelatin stimulates the growth of spleen cells in
      vitro. Tritium thymidine (3H-TdR) uptake into phytohemagglutinin (PHA)-stimulated
      spleen cells as well as intact spleen cells was augmented by gelatin. These
      findings suggest that gelatin serves as a mitogen for lymphoid cells. In this
      study, the target of action of gelatin was investigated. Tritium thymidine uptake
      into T cell-rich fraction was enhanced by incubation with 7.5 mg/ml of gelatin
      for 48 hours. The level of 3H-TdR uptake into B cell-rich fraction was not
      definitely increased by gelatin. Flow cytometric analysis confirmed these
      findings. Namely, it showed that treatment of spleen cells with 7.5 mg/ml gelatin
      increased a ratio of CD3-positive cells and decreased that of CD19-positive
      cells. Tritium thymidine uptake into natural killer cell-rich fraction was
      augmented by gelatin in a similar fashion to T cell-rich fraction. Tritium
      thymidine uptake into macrophages was very low and not affected by gelatin.
      Tritium thymidine uptake into macrophage-precursors was very low but was enhanced
      by gelatin. These findings suggest that gelatin could be used as an agent of
      cancer biotherapy.

PMID- 10941537
TI  - Effect of cisplatin-based chemotherapy on emergence of cisplatin resistance, and
      its correlation with intracellular glutathione levels and accumulation of p53
      protein in human ovarian cancer.
AB  - Forty-seven ovarian cancer cases in which 20 were previously treated with
      cisplatin (cisPt) based chemotherapy, were checked for in vitro chemosensitivity
      using MTT assay. The drugs included in the study were cisPt, adriamycin (ADR),
      epirubicin (EPR) and etoposide (ETO). The logarithemic concentrations (0.1, 1.0,
      10.0 and 100.0 micrograms/ml) of these drugs were used in the MTT assay. The IC50
      values for these drugs in the above tumor samples were calculated. The effect of
      pretreatment with cisPt based chemotherapy on the emergence of drug resistance,
      expression of p53 protein (detected using immunohistochemical method by employing
      monoclonal antibody to p53) and intracellular glutathione (GSH) levels was also
      studied. Our results demonstrated the superiority of EPR in terms of its efficacy
      as compared to the other drugs used in the study. EPR was effective in both,
      previously cisPt-exposed and cisPt-unexposed ovarian cancer cases indicating its
      importance as a second line chemotherapy in the refractory ovarian carcinoma
      cases. Pre-exposure to cisPt based chemotherapy appears to result in the
      emergence of cisPt resistance, elevated intracellular GSH levels as well as p53
      positivity. A statistically significant correlation was also observed between ADR
      and EPR resistance and p53 positivity (P < 0.01 and 0.05 respectively).

PMID- 10941536
TI  - Involvement of lipid peroxidation, oncogene expression and induction of apoptosis
      in the antitumorous activity of ferric-sorbitol-citrate.
AB  - We described before that iron-containing, anti-anaemic drug, ferric-sorbitol
      citrate complex (FSC) inhibited proliferation of various murine cancer cells in
      vitro and caused tumour regression in vivo, but did not affect proliferation of
      the non-malignant cells. The aim of this study was to evaluate further the
      anticancer activity mechanism of FSC using human colon cancer cell line CaCo2.
      After treatment with FSC for 72 hours impaired proliferative ability and
      viability of CaCo2 cells as observed. Growth modification caused by FSC involved
      diminished expression of Bcl-2, and over-expression of mp53 proto-oncogenes,
      accompanied by increased incidence of apoptosis. Immunostaining the cells
      applying monoclonal antibodies for lipid peroxidation product 4-hydroxynonenal
      (HNE) showed that FSC-iron increased intracellular HNE, but did not induce severe
      HNE-mediated oxidative stress. Thus, antitumorous mechanism of FSC involves
      modulation of oncogene expression and induction of apoptosis apparently not
      triggered by lipid peroxidation-mediated oxidative stress, although FSC might
      restore endogenous HNE production in the CaCo2 cells to level resembling
      physiological for various non-malignant cells and tissues. Higher dose of FSC
      increased also number of intracellular ferritin positive CaCo2 cells.

PMID- 10941539
TI  - Assessing ventricular function.

PMID- 10941538
TI  - Predicting mitral regurgitation following percutaneous mitral valvotomy with the
      Inoue balloon: comparison of two echocardiographic scoring systems.

PMID- 10941540
TI  - Recent advances in dobutamine stress echocardiography.
AB  - Dobutamine stress echocardiography (DSE) is a reliable cardiac risk stratifier
      that has widespread applicability because of its clinical accuracy and cost
      effectiveness. Dobutamine has positive inotropic and chronotropic effects and is
      commonly used in patients who cannot exercise or achieve an adequate heart rate
      response with exercise. Recently available long-term results from several
      independent clinical trials, combined with enhancements in image quality, have
      improved the ability to detect significant coronary artery disease and determine
      myocardial viability. Dobutamine stress echocardiography has an excellent safety
      profile with clinical results superior to regular exercise electrocardiography
      and comparable with exercise echocardiography and radionucleotide perfusion
      stress imaging. Low-dose dobutamine response can accurately predict dysfunctional
      yet viable myocardial regions that may improve with revascularization. Clinical
      studies are now available refining the common use of DSE preoperatively in female
      patients with valvular disease, as well as in the emergency department.
      Dobutamine stress echocardiography does have some limitations in discriminating
      particular regions of ischemia when multiple ventricular segments are involved
      and when the imaging is suboptimal. It can be applied using minimal additional
      resources in an otherwise functioning echocardiography laboratory and, with
      appropriate training, can result in clinical results comparable with those of
      large-scale multicenter trials. Ongoing improvements in technology and the
      development of new reagents such as myocardial contrast agents hold promise for
      further advancement in the near future.

PMID- 10941541
TI  - A comparison of brachial artery flow-mediated vasodilation using upper and lower
      arm arterial occlusion in subjects with and without coronary risk factors.
AB  - BACKGROUND: The ultrasound assessment of brachial artery flow-mediated
      vasodilation provides a noninvasive means for measuring endothelial function. The
      test is performed using either upper or lower arm blood pressure cuff arterial
      occlusion to induce hyperemia. Upper arm occlusion produces a greater hyperemic
      stimulus. Brachial artery flow-mediated vasodilation is abnormal in the presence
      of coronary risk factors. HYPOTHESIS: The study sought to compare the ability of
      the upper and lower arm occlusion techniques to differentiate endothelial
      function in subjects with and without risk factors. METHODS: We measured brachial
      artery flow-mediated vasodilation in 20 subjects, 10 without and 10 with a single
      risk factor (hypertension, hypercholesterolemia, or cigarette smoking) using both
      the upper and lower arm occlusion techniques (5 min blood pressure cuff
      occlusion). Using 11 MHz ultrasound, Doppler blood flow velocities were measured
      before and immediately after cuff deflation. Brachial artery vasodilation was
      measured 1 min after cuff deflation, compared with baseline, and expressed as a
      percent increase. RESULTS: The immediately postocclusion hyperemia (% increase in
      flow) was significantly greater (p < 0.01) using the upper versus the lower arm
      technique in both the normal (530 +/- 152 vs. 383 +/- 51%) and the risk factor
      (583 +/- 153 vs. 409 +/- 114%) groups. Flow-mediated vasodilation was
      significantly greater (p < 0.01) using the upper arm versus the lower arm
      occlusion technique in both the normal (13.4 +/- 5.3 vs. 5.6 +/- 3.4%) and risk
      factor (7.9 +/- 3.6 vs. 3.9 +/- 2.2%) groups. Vasodilation was significantly
      greater (p < 0.01) in the normal subjects than in the risk factor subjects (13.4
      +/- 5.3 vs. 7.9 +/- 3.6%) using the upper arm technique, but was not
      statistically different in the two groups using the lower arm technique.
      CONCLUSIONS: Our study demonstrates that upper arm compared with lower arm cuff
      occlusion undertaken to induce hyperemia for the assessment of brachial artery
      flow-mediated vasodilation results in significantly greater hyperemia and
      vasodilation. Flow-mediated vasodilation obtained using the upper arm technique
      better separates subjects with and without coronary risk factors.

PMID- 10941542
TI  - High variability of retrograde fast pathway sensitivity to adenosine.
AB  - BACKGROUND: Adenosine is widely used as a tool to assess the effectiveness of
      radiofrequency ablation of concealed accessory pathways. HYPOTHESIS: The goal of
      this study was to determine the reliability of this test by studying the
      retrograde fast pathway sensibility in a large patient population with typical
      atrioventricular (AV) nodal reentry tachycardias. We sought also to determine
      whether AV nodal properties were predictive of a retrograde fast pathway
      sensitivity to adenosine. METHODS: In all, 124 patients with inducible AV nodal
      reentrant tachycardia were included in this study. All patients received a
      clinically used standard dose of 12 mg adenosine during ventricular pacing, with
      500 ms and a constant ventriculoatrial (VA) conduction via the fast pathway.
      Electrophysiologic parameters of the AV node were determined in all patients in
      order to correlate them with the adenosine sensitivity of the retrograde pathway.
      RESULTS: In 74 patients, the injection of 12 mg adenosine resulted in a transient
      VA block, whereas no VA block occurred in the remaining 50 patients. In two
      patients, concealed accessory pathways were unmasked after the injection of
      adenosine. The adenosine sensitivity of the retrograde fast pathway was
      associated with longer retrograde conduction times and cycle lengths during AV
      nodal reentrant tachycardias. CONCLUSION: This study shows a high variability of
      retrograde fast pathway sensitivity to adenosine. Thus, in 40% of patients the
      lack of VA block after adenosine injection is not specific for persistent
      accessory pathway function after radiofrequency ablation. Electrophysiologic
      properties of patients with AV nodal reentrant tachycardias were different in
      patients with and without adenosine-sensitive retrograde fast pathways, possibly
      indicating differential patterns of penetration of the retrograde fast pathway
      into the compact AV node.

PMID- 10941544
TI  - Increased platelet activation and endothelial dysfunction in patients with atrial
      fibrillation immediately following percutaneous balloon mitral valvuloplasty.
AB  - BACKGROUND: Immediately following percutaneous balloon mitral valvuloplasty
      (PBMVP), patients have a 3% risk of systemic thromboembolism. HYPOTHESIS: We
      hypothesized that this may in part be due to an increase in hypercoagulability
      (as indicated by abnormal coagulation, platelet activation, and endothelial
      dysfunction) in such patients. METHODS: We measured indices of platelet
      activation [soluble P-selectin (sPsel), ELISA], endothelial dysfunction [von
      Willebrand factor (vWf), ELISA], and coagulation (fibrinogen, modified Clauss) in
      16 patients (15 women, mean age 59 +/- 10 years) with chronic atrial fibrillation
      admitted for PBMVP, and 16 healthy age- and gender-matched controls. Blood
      samples were obtained as follows: (1) peripheral venous samples prior to PBMVP,
      immediately following PBMVP, and 24 h after PBMVP; and (2) arterial samples prior
      to and immediately following PBMVP. RESULTS: Patients with mitral stenosis and
      chronic atrial fibrillation demonstrated significantly higher mean levels of vWf
      [148 (SD 24) vs. 102 (SD 37); t-test, p < 0.001] and plasma fibrinogen [4.2 (SD
      0.8) vs. 3.3 (SD 0.8); p = 0.003] at baseline than matched healthy controls.
      There was a nonsignificant trend toward lower median sP-sel levels in patients
      with mitral stenosis [64 (inter quartile range 47-91) vs. 109 (46-128); Mann
      Whitney test, p = 0.08]. Following PBMVP, there was a significant increase in
      venous sP-sel levels immediately post procedure (paired Wilcoxon test, p = 0.03)
      and at 24 h afterward (p = 0.01). Arterial s-Psel levels correspondingly
      increased immediately post procedure (p = 0.008). There was a significant
      increase in mean venous (at 24 h) but not arterial vWf levels post PBMVP. There
      were no significant changes in mean venous or arterial plasma fibrinogen levels
      following PBMVP. CONCLUSION: Patients with mitral stenosis and chronic atrial
      fibrillation have increased plasma levels of vWf and fibrinogen levels compared
      with healthy controls, suggesting increased endothelial dysfunction and
      coagulation at baseline in these patients. The increased levels of sP-sel
      immediately post procedure and at 24 h, in association with increased vWf levels
      at 24 h after PBMVP, are in keeping with an increase in platelet activation and
      endothelial dysfunction following PBMVP. These changes may contribute to the
      increased risk of thromboembolism following PBMVP and suggest the need for
      adequate antithrombotic therapy following PBMVP.

PMID- 10941543
TI  - Clinical and nonclinical correlates of racial and ethnic differences in
      recommendation patterns for coronary revascularization.
AB  - BACKGROUND: We sought to determine whether gender or racial differences exist in
      recommendations for coronary revascularization in a multiracial patient
      population undergoing their first coronary angiography at an academic institution
      from 1990-1993 for the evaluation of coronary artery disease (CAD). HYPOTHESIS:
      For patients with clinically significant CAD, no racial differences exist in the
      recommendation to revascularization following coronary angiography. METHODS: The
      main outcome measure was a recommendation for coronary revascularization such as
      percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass
      graft (CABG) for patients with clinically significant CAD (n = 590). The primary
      multiple logistic regression analysis focused on only those patients with
      angiographically severe disease, defined as triple-vessel or left main CAD (n =
      180). Race was trichotomized into Hispanic, black, and white to ascertain whether
      any differential effects of race/ethnicity existed while controlling for age,
      gender, ejection fraction, angina, diabetes, hypertension, and peripheral
      vascular disease. A medical record review for all patients with severe CAD, who
      were given a recommendation for medical therapy, was conducted to ascertain
      whether previously unmeasured clinical factors or nonclinical factors may have
      precluded a PTCA/CABG recommendation. RESULTS: Hispanics with severe disease were
      significantly less likely than whites to be given a recommendation for PTCA/CABG
      following angiography [odds ratio (OR) = 0.39; 95% confidence interval (CI)
      (0.17, 0.92)]. Blacks were 67% as likely as whites to be given such a
      recommendation [OR = 0.67; 95% CI (0.17, 2.71)]. Medical records, reviewed for 35
      of 40 of these patients given a recommendation for medical therapy, revealed that
      6 patients eventually had PTCA/CABG within 6 months due to precipitating ischemic
      events; 9 had such severe or diffuse disease that revascularization did not
      appear to be an alternative, and 2 patients opted for medical therapy.
      CONCLUSIONS: Racial differences were manifested in the recommendations made
      following angiography and may be explained by previously unmeasured clinical as
      well as nonclinical factors.

PMID- 10941545
TI  - Medical management of significant coronary angiographic stenoses: outcome of 60
      patients observed for 433 patient years.
AB  - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has become
      routine in the management of patients with stable angina pectoris and significant
      coronary stenoses, while medical management of such patients has declined.
      HYPOTHESIS: The purpose of the present study was to evaluate the outcome of 60
      patients at the Virginia Heart Institute with stable angina pectoris, observed
      between 1976 and 1997, who had documented evidence of severe angiographic disease
      but were elected to be monitored and managed in an outpatient pharmacologic
      rehabilitation program. METHODS: Sixty patients with significant stenoses by
      coronary angiography (21 with single-vessel, 26 with double-vessel, and 13 with
      triple-vessel) without impaired ventricular function, exercise-induced ischemia
      or hypotension, limited exercise performance, malignant arrhythmias, or drug
      intolerance were enrolled in a program of pharmacologic rehabilitation and
      observed for an average of 7.2 years. RESULTS: Among the 60 patients, there were
      6 deaths at a mean interval of 8.3 years. Two deaths were in patients ineligible
      for revascularization. Another patient who died had refused revascularization
      after new-onset left ventricular dysfunction, and another died intraoperatively
      during abdominal aortic aneurysm repair. Two patients died while exercising.
      Thirteen patients underwent follow-up catheterization for worsening angina; 11 of
      13 showed progression, predominantly from new lesions. Four of 11 were referred
      for revascularization; 7 of 11 continued medical treatment; 49 patients were
      stable on medical therapy throughout the period of observation. CONCLUSION:
      Medical management of selected patients with significant coronary stenoses is
      safe and effective.

PMID- 10941546
TI  - Immediate and late clinical and angiographic outcomes after GFX coronary
      stenting: is high-pressure balloon dilatation necessary?
AB  - BACKGROUND: The GFX stent is a balloon-expandable stent made of sinusoidal
      element of stainless steel. The adjunct high-pressure balloon dilatations were
      usually recommended in routine stenting procedure. HYPOTHESIS: The aim of this
      study was to evaluate the immediate and long-term clinical and angiographic
      outcomes and to investigate the necessity of high-pressure balloon dilatation
      during GFX stenting. METHODS: In all, 172 consecutive patients underwent single
      12 or 18 mm GFX stent implantation in 188 native coronary lesions. Two types of
      stenting technique were used: (1) stent size of a final stent-to-artery ratio of
      1:1 (inflation pressure > 10 atm, high-pressure group), and (2) stent size of 0.5
      mm bigger than reference vessel (inflation pressure < or = 10 atm, low-pressure
      group). The adjunct high-pressure balloon dilatations were performed only in
      cases of suboptimal results. RESULTS: The adjunct high-pressure balloon
      dilatation was required in 11 of 83 lesions (13%) in the high-pressure group and
      in 7 of 105 lesions (7%) in the low-pressure group (p = 0.203). Procedural
      success rate was 100%. There were no significant differences of in-hospital and
      long-term clinical events between the two groups. The overall angiographic
      restenosis rate was 17.7%; 18.4% in the high-pressure group and 17.1% in the low
      pressure group (p = 0.991). CONCLUSIONS: The GFX stent is a safe and effective
      device with a high procedural success rate and favorable late clinical outcome
      for treatment of native coronary artery disease. Further randomized trials may be
      needed to compare stenting techniques in GFX stent implantation.

PMID- 10941547
TI  - Changes of the T-wave amplitude and angle: an early marker of altered ventricular
      repolarization in hypertension.
AB  - BACKGROUND: The heterogeneity of ventricular repolarization is an important
      proarrhythmic factor. QT dispersion has been proposed to reflect the
      inhomogeneity of ventricular repolarization, but a poor reproducibility limits
      its clinical applicability. Reliable noninvasive methods to quantify
      abnormalities in ventricular repolarization are still lacking. The T-loop
      morphology analysis is a novel method aimed at quantifying ventricular
      repolarization. HYPOTHESIS: To test the ability of the T-loop morphology analysis
      to discriminate between hypertensive patients and healthy subjects, 105
      hypertensive patients (mean age 63.6 +/- 12.3 years) and 110 healthy controls
      (mean age 49.7 +/- 14.3 years) were evaluated. METHODS: The maximum QT interval
      (QT maximum), the minimum QT interval (QT minimum), and their difference (QT
      dispersion) were calculated from a digitally recorded 12-lead electrocardiogram
      (ECG) in both study groups. X, Y, and Z leads were reconstructed from the 12-lead
      ECG, and the amplitude of the maximum T vector (T amplitude) and the angle
      between the maximum T vector and X axis (T angle) were calculated from the
      projection of the T loop in the frontal plane. RESULTS: T amplitude (p < 0.001),
      T angle (p = 0.05), and QT dispersion (p = 0.04) were significantly different
      between hypertensive patients and controls, while QT maximum (p = 0.14) and QT
      minimum (p = 0.35) did not differ between the groups. T amplitude was the only
      marker which differed between hypertensive patients without ECG criteria for left
      ventricular hypertrophy and controls (p = 0.002). CONCLUSIONS: T-loop features
      and particularly T amplitude are significantly different between hypertensive
      patients and healthy controls and may serve as early markers of repolarization
      abnormalities in a hypertensive population.

PMID- 10941549
TI  - Exercise conditioning and heart rate variability: evidence of a threshold effect.
AB  - BACKGROUND: A protective effect of exercise in preventing sudden cardiac death is
      supported by studies in healthy populations as well as in patients with cardiac
      disease. The mechanisms involved in this protective effect are unknown.
      HYPOTHESIS: We hypothesized that exercise conditioning would beneficially alter
      autonomic nervous system tone, measured by heart rate variability. METHODS: We
      prospectively studied 20 cardiac patients enrolled in a Phase 2 12-week cardiac
      rehabilitation program following a recent cardiac event. The patients underwent
      24 h Holter monitoring at program entry and 12 weeks later. Heart rate
      variability analysis was assessed for both time domain and spectral analysis.
      RESULTS: The group demonstrated a modest mean conditioning effect, indicated by
      an average reduction in resting heart rate from 81 +/- 16 to 75 +/- 12 beats/min
      (p = 0.03), and an increase in training METS from 2.1 +/- 0.4 to 3.3 +/- 1.1 (p <
      0.0001). Overall, 15 of 20 (75%) patients demonstrated increased total and high
      frequency power, and mean high-frequency power was significantly increased (3.9
      +/- 1.4 vs. 4.4 +/- 1.0 ln, p = 0.05). When stratified according to the magnitude
      of exercise conditioning, patients achieving an increase of > 1.5 training METS
      demonstrated significant increases in SDNN, SDANN index, SDNN index, pNN50, total
      power, and high-frequency power (all p < 0.05) (see text for explanation of
      abbreviations). CONCLUSIONS: Exercise conditioning improves heart rate
      variability in cardiac patients, particularly in patients who achieve a threshold
      of > 1.5 training METS increase over a 12-week period. These study results are
      supportive of the concept that exercise training lowers the risk of sudden
      cardiac death via increased vagal tone, which likely beneficially alters
      ventricular fibrillatory and ischemic thresholds.

PMID- 10941548
TI  - Left ventricular myocardial remodeling and contractile state in chronic aortic
      regurgitation.
AB  - BACKGROUND: In chronic aortic regurgitation, eccentric hypertrophy, with combined
      concentric hypertrophy of the left ventricle, is an important adaptive response
      to volume overload, which in itself is a compensatory mechanism for permitting
      the ventricle to normalize its afterload and to maintain normal ejection
      performance (physiologic hypertrophy). However, progressive dilatation of the
      left ventricle leads to depressed left ventricular (LV) contractility and
      myocardial structural changes, including cellular hypertrophy and interstitial
      fibrosis (pathological hypertrophy). HYPOTHESIS: The study was undertaken to
      determine the relationship between left ventricular myocardial structure and
      contractile function in 14 patients with chronic aortic regurgitation by cardiac
      catheterization and endomyocardial biopsies. METHODS: Myocardial cell diameter
      and percent interstitial fibrosis were obtained from biopsy samples. Contractile
      function was evaluated from the ratio of end-systolic wall stress to end-systolic
      volume index (ESS/ESVI) and the ejection fraction-end-systolic stress (EF-ESS)
      relationship, which was obtained from 30 normal control subjects. RESULTS:
      Myocardial cell diameter correlated significantly with the ESVI (r = 0.72, p <
      0.005), ejection fraction (r = -0.58, p < 0.05), and ESS/ESVI (r = -0.58, p <
      0.05). The percent interstitial fibrosis also correlated inversely with ESS/ESVI
      (r = -0.71, p < 0.005). Compared with very few patients with an ESVI < 70 ml/m2,
      the majority of patients with ESVI > or = 70 ml/m2 had a cell diameter of > or =
      30 microns and a percent interstitial fibrosis of > or = 10%. The nine patients
      who had depressed contractile function, as assessed from the EF-ESS relationship,
      had a higher percent interstitial fibrosis (p < 0.05) than five patients showing
      a normal EF-ESS relationship, despite the fact that there was no significant
      difference in myocardial cell diameter between them. Thus, advanced cellular
      hypertrophy and excessive interstitial fibrosis were significantly and
      independently associated with myocardial contractile dysfunction and appeared to
      be responsible for ventricular remodeling. CONCLUSION: Our findings suggest that
      in many patients with aortic regurgitation, eccentric hypertrophy changes its
      nature from physiologic to nonphysiologic during the earlier stages in the course
      of the disease rather than during the stage described previously.

PMID- 10941550
TI  - Influence of angiotensin-converting enzyme gene polymorphism on development of
      athlete's heart.
AB  - BACKGROUND AND HYPOTHESIS: Genetic influence on development of athlete's heart is
      uncertain. This study investigated whether angiotensin-converting enzyme (ACE)
      gene polymorphism influenced development of athlete's heart. METHODS: Forty-three
      participants in a 100-km ultramarathon were classified on the basis of ACE gene
      polymorphism into a deletion group (n = 26) and an insertion group (n = 17).
      Echocardiograms were recorded to determine left ventricular end-diastolic and end
      systolic diameters, interventricular septal thickness, left ventricular posterior
      wall thickness, left ventricular mass, and ejection fraction. RESULTS: Left
      ventricular end-diastolic diameter (65.5 +/- 4.0 mm) and left ventricular mass
      (369.5 +/- 73.9 g) were significantly larger in the subjects with deletion than
      in those with insertion (57.4 +/- 4.2 mm, 306.5 +/- 93.7 g). However, no
      significant differences in the other parameters were noted. CONCLUSIONS: In long
      distance runners, ACE gene polymorphism of the D/D and D/I genotypes has a
      stronger influence on left ventricular hypertrophy than polymorphism of the I/I
      genotype.

PMID- 10941551
TI  - True-positive exercise electrocardiogram/false-negative thallium-201 scintigram:
      a proposal of a mechanism for the paradox.
AB  - A 72-year-old man with exertional angina had a strongly positive exercise
      electrocardiogram (EECG) with a negative thallium-201 myocardial perfusion
      scintigram (Tl). Arteriography revealed triple-vessel coronary artery disease,
      for which he underwent aortocoronary bypass grafting. Repeat EECG was negative,
      and it was again associated with a negative Tl. The false-negative Tl on the
      first test was felt to be due to a rare phenomenon of homogeneously distributed
      reversible exercise-induced myocardial ischemia, leading to a uniform radiotracer
      count density. The even distribution of ischemia would also be expected to render
      a false-negative EECG, due to electrocardiographic cancellation, and this is
      frequently the case. However, in the patient presented herein, we propose that
      the ischemic cardiac apex rendered the EECG strongly positive because its
      position was not opposed by an ischemic muscular region, and thus an uncancelled
      ischemic ST-segment vector was generated. This hypothesis is supported by our
      recent work showing the unique role of the ischemic apex (among all the other
      myocardial territories) in rendering the EECG positive.

PMID- 10941552
TI  - Ruptured papillary muscle with unilateral pulmonary edema.

PMID- 10941553
TI  - David Scherf.

PMID- 10941554
TI  - An overview of the epidemiology of cutaneous melanoma.
AB  - Incidence of cutaneous melanoma has increased over the last several decades.
      Screening for melanocytic lesions is an effective approach to reducing incidence.
      This article presents information useful in melanoma screening, including
      histologic types of tumors, measurements, and anatomic sites. Causes of tumors,
      including ultraviolet radiation and the role of steroid hormones, are discussed.
      In addition, the presence of atypical and benign nevi is addressed.

PMID- 10941555
TI  - Melanoma. Screening and education.
AB  - Identification of early and thin cutaneous melanoma has a significant impact on
      overall survival. Through education efforts physicians, health care providers,
      and the public can identify risk categories that may benefit from screening.
      Early detection and screening efforts may have a number of barriers to overcome,
      but ultimately should lead to an overall reduction of mortality.

PMID- 10941556
TI  - Under the microscope. Surgeons, pathologists, and melanocytic nevi.
AB  - Predicting the biologic behavior of melanocytic neoplasms (benign versus
      malignant) based on histology is one of the most difficult challenges in surgical
      pathology and dermatology. Success in the field of melanocytic neoplasia can be
      achieved by two means: performing excisions or biopsies that maximize the
      obtainable histologic information and providing sufficient history.

PMID- 10941557
TI  - Malignant melanoma, dysplastic melanocytic nevi, and Spitz tumors. Histologic
      classification and characteristics.
AB  - The classification and pertinent histopathologic features of cutaneous melanoma,
      dysplastic melanocytic nevi, and Spitz tumors are presented. A discussion on
      melanoma emphasizes an objective approach to classification based on
      histomorphologic features including location in the skin, disposition and
      frequency of melanocytes, other specific morphologic features, and cell type.
      Other topics addressed include common and unusual variants of melanoma, the use
      of immunohistochemistry, and the histopathologic reporting of melanoma.

PMID- 10941558
TI  - Clinical classification and staging.
AB  - The identification of increasingly powerful prognostic factors has led to
      sequential modifications of the cutaneous melanoma staging system. Changes in the
      staging system are anticipated as more refined prognostic factors are identified.
      This article provides an overview of the system, including a brief history and an
      introduction to recent advances in staging of patients with primary melanoma
      (i.e., sentinel lymphadenectomy). Practical recommendations for a stage-specific
      workup for the patient, which are especially important given the need for quality
      care in an increasingly cost-conscious environment, are provided.

PMID- 10941559
TI  - Staging work-up and post-treatment surveillance of patients with melanoma.
AB  - Strategies based on evidence are required to accurately stage and effectively
      follow patients with melanoma. The goal of staging is to define the extent of
      disease at the time of presentation to direct and assign prognosis. Patient
      surveillance is performed to assess treatment results and detect recurrences
      amenable to further treatment. Staging and surveillance require careful use of
      resources to be cost effective. This article addresses preoperative staging and
      post-treatment surveillance of patients with melanoma and outlines a method of
      follow-up based on available data.

PMID- 10941560
TI  - The clinical spectrum of pigmented lesions.
AB  - This article presents the clinical features of a spectrum of pigmented lesions.
      It begins with benign lesions that may be confused with melanocytic nevi, such as
      lentigines, seborrheic keratoses, and dermatofibromas. The next section focuses
      on the various types of melanocytic nevi, including congenital, blue, and Spitz
      nevi. A description of atypical nevi is provided, followed by an outline of the
      clinical characteristics of each subtype of cutaneous melanoma. The clinical
      characteristics of various pigmented lesions are illustrated.

PMID- 10941561
TI  - Surgical management of the primary melanoma.
AB  - Conservative margins of resection have proven safe for malignant melanomas
      arising in a wide variety of anatomic sites. Reconstruction, however, can be a
      challenge in cosmetically sensitive areas. This article summarizes the authors'
      management philosophy, including reconstruction.

PMID- 10941562
TI  - Lymphatic mapping and sentinel lymph node biopsies.
AB  - Once melanoma cells leave the skin and travel to the lymph nodes, they have
      metastasized, thereby reducing chances for the patient's long-term, disease-free
      survival. Methods for tracing and removing lymph nodes include elective lymph
      node dissection, lymphoscintigraphy, and sentinel lymph node biopsy. This article
      reviews the concepts, procedures, and effectiveness of these techniques.

PMID- 10941563
TI  - Regional lymph node dissections in malignant melanoma.
AB  - Considerable controversy surrounds the application of regional lymphadenectomy in
      the treatment of cutaneous melanoma in patients with clinically negative nodes;
      however, therapeutic lymph node dissection for clinically positive nodes has
      shown clear benefits. Opponents of elective lymph node dissection (ELND) for
      clinically negative nodes believe that because 80% of patients with clinical
      Stage I disease have histologically negative nodes at the time of resection of
      the primary tumor, prophylactic excision of the regional nodes is unnecessary.
      Some clinicians have failed to demonstrate a survival advantage for ELND. With
      the recent introduction of sentinel lymph node dissection, it may be possible to
      select patients who are likely to benefit from ELND. The authors recommend ELND
      based on the identification of metastatic cells within the sentinel lymph node in
      all patients with primary melanomas with a thickness of at least 1.0 mm.

PMID- 10941564
TI  - The use of isolated limb perfusion to manage recurrent malignant melanoma.
AB  - Hyperthermic isolated limb perfusion (ILP) effectively treats locally recurrent
      metastatic disease in malignant melanoma of the extremities. The goal of ILP is
      to decrease the rate of further recurrent disease and eradicate tumor load to
      achieve wound hygiene and preservation of limb function. This article reviews the
      development over the last 45 years of ILP in the treatment of malignant melanoma,
      describes the surgical technique of ILP, and reviews the results of clinical
      trials with various chemotherapeutic agents. It discusses the recent addition of
      tumor necrosis factor alpha to the list of drugs currently being explored in
      hyperthermic ILP, in the ongoing attempt to improve the treatment for recurrent
      malignant melanoma of the extremities.

PMID- 10941565
TI  - Systemic chemotherapy.
AB  - The main use of systemic chemotherapy in metastatic melanoma remains palliative.
      Dacarbazine (dimethyl-1-triazeno imidazole-4-carboxamide [DTIC]) is the standard
      chemotherapy agent for advanced disease. The combination chemotherapy and
      biochemotherapy regimens have achieved higher response rates, but have not led to
      durable remission or improved survival. The field of systemic therapy remains in
      need of a more effective and less toxic treatment strategy.

PMID- 10941566
TI  - Systemic treatment of malignant melanoma.
AB  - Once there is evidence of systemic involvement in malignant melanoma, treatment
      options become severely limited and the disease is virtually incurable. There
      are, however, options available to treat patients, including single-agent
      chemotherapy, single-agent biologic response modifier (BRM), combination
      chemotherapy, and the combination of chemotherapeutic agents and BRMs. These
      treatment modalities and their indications for use are discussed.

PMID- 10941567
TI  - Epidemiology and pathology of Densovirinae.

PMID- 10941568
TI  - Molecular biology of Densovirinae.

PMID- 10941569
TI  - Densovirinae as gene transfer vehicles.
AB  - Densoviruses present an attractive opportunity to develop expression vectors for
      insects. They exhibit several features that are beneficial for such vectors. The
      genomes of densoviruses are among the smallest of animal DNA viruses, and,
      therefore are easier to use for cloning and transfection procedures. The fact
      that cloned densovirus genomes are infectious greatly simplifies their
      applications. It seems that both densovirus promoters have high constitutive
      activity and they can be further transactivated with NS. The major nonstructural
      protein, NS1, can retain its functions even if fused to a foreign protein. If the
      recombinant genome carrying a gene of interest is supplied with the missing virus
      functions, it can be packaged into transducing particles. The packaging capacity
      of the densovirus particles can accommodate a foreign gene encoding a polypeptide
      of up to 150 kDa. Finally, the functions missing from the recombinant densovirus
      genome that are necessary for the production of transducing particles can be
      supplied in several different ways: they can be expressed from a helper plasmid,
      in cells transformed with the virus genes, or from an RNA virus. The last two
      methods produce transducing particles which are free of wild type virus.
      Densovirus transducing particles can be used for the delivery and expression of a
      gene of interest in insect cell culture or living insects. Transducing particles
      expressing reporter genes can be valuable tools in the study of viral
      pathogenesis and perhaps in the genetic manipulation of insects.

PMID- 10941570
TI  - Infectiology and pathology of human adeno-associated viruses.

PMID- 10941571
TI  - Molecular biology of adeno-associated viruses.

PMID- 10941572
TI  - Adeno-associated viruses as gene transfer vehicles.

PMID- 10941573
TI  - Epidemiology and pathology of erythroviruses.

PMID- 10941574
TI  - Molecular biology of erythroviruses.

PMID- 10941575
TI  - Erythroviruses as gene transfer vehicles.

PMID- 10941576
TI  - Epidemiology and pathology of autonomous parvoviruses.

PMID- 10941577
TI  - Molecular biology of autonomous parvoviruses.

PMID- 10941578
TI  - Autonomous parvoviruses as gene transfer vehicles.

PMID- 10941579
TI  - Airway management and direct laryngoscopy. A review and update.
AB  - Direct laryngoscopy is the direct visualization of the larynx while using a rigid
      laryngoscope to distract the structures of the upper airway. This article reviews
      the anatomy relevant to laryngoscopy and then presents a stepwise approach to the
      procedure. Alternative intubation techniques, positioning, laryngoscopy blades,
      and stylets are then covered. Pharmacologic adjuncts are discussed briefly as
      they relate to the difficult airway and incorporation into overall airway
      management.

PMID- 10941580
TI  - Emergent airway management. Indications and methods in the face of confounding
      conditions.
AB  - Optimal airway management requires an experienced caregiver, attention to detail,
      and knowledge of the patient's physiology. A variety of pharmacologic agents have
      proved useful in obtaining a secure airway and minimizing risk to the patient.
      Depending on the skills of the caregiver, oral intubation has become the
      preferred means of airway control in most patients. Advances in technique,
      equipment, and pharmacology have greatly improved the art of airway management;
      however, there is no substitute for an experienced clinician.

PMID- 10941581
TI  - Emergent management of the airway. New pharmacology and the control of
      comorbidities in cardiac disease, ischemia, and valvular heart disease.
AB  - Once it is decided that the patient in distress requires tracheal intubation, the
      primary goal is to secure the airway as quickly and safely as possible to assure
      adequate oxygenation and ventilation. The clinician should quickly review the
      patient's history, physical examination findings, and laboratory data to
      determine the presence of cardiovascular disease, assess intravascular volume
      status, and formulate a plan for induction of anesthesia. The stresses of
      hypoxia, hypercarbia, acidosis, and extreme fatigue result in near-maximal
      sympathetic outflow that is manifest as tachycardia, labile blood pressure, and
      increased myocardial contractility. The astute clinician should anticipate that
      the tachycardia and hypertension associated with laryngoscopy and tracheal
      intubation is followed by a period of hypotension. This postintubation
      hypotension results from the acute marked attenuation of the sympathetic tone
      associated with resolution of hypoxia and hypercarbia, direct drug-induced
      negative inotropic effect, and vasodilation. The decrease in sympathetic vascular
      tone may result in hypotension by exacerbating the decrease in cardiac preload
      and afterload from hypovolemia. In addition, the use of positive pressure
      ventilation and positive end-expiratory pressure (PEEP) in these hypovolemic
      patients will further decrease ventricular preload by impeding venous return,
      leading to profound hypotension. Several pharmacologic agents are required to
      treat effectively the hemodynamic perturbations associated with induction,
      laryngoscopy, and tracheal intubation. Most sedative hypnotic agents that are
      administered for induction provide minimal to no analgesia. Patients are most
      often given a combination of drugs to provide adequate sedation, analgesia to
      blunt the noxious stimuli, and muscle relaxation to facilitate the laryngoscopy.
      The major challenge is to choose a combination of drugs that at the appropriate
      doses, effectively blunt the responses to intubation without contributing to
      postlaryngoscopy hypotension. One can use several strategies to accomplish these
      goals; administration of a narcotic analgesic before induction decreases the dose
      of induction agent and can attenuate the sympathetic response to intubation.
      Because of the prevalence of cardiovascular disease and hypovolemia in this
      population of patients, all chosen drugs should have minimal negative effect on
      cardiac function and patients with hypovolemia should be hydrated. Most clinical
      studies have been performed in hemodynamically stable patients, so the routine
      dosages of sedative hypnotics should be reduced substantially and titrated to
      effect. An additional strategy is to treat significant hemodynamic perturbations
      with vasopressors, vasodilators, short-acting selective beta-1 blockers, and
      inotropic agents. The choice of vasoactive agent depends on the magnitude of the
      hemodynamic response and the presence of specific underlying cardiovascular
      pathology.

PMID- 10941582
TI  - Bridges to establish an emergency airway and alternate intubating techniques.
AB  - In this article, a number of alternatives to direct laryngoscopy are examined.
      These alternatives include the laryngeal mask airway (LMA; LMA North America, San
      Diego, CA), cuffed oropharyngeal airway (COPA; Mallinckrodt, St. Louis, MO), and
      Combitube (Kendall-Sheridan, Mansfield, MA), that have been designed to act as
      bridges to establish an airway. Other devices, such as rigid stylets, the
      lightwand (a blind technique) and indirect fiberoptic rigid stylets, such as the
      Bullard scope, Upsher scope, and Wu scope are also briefly discussed.

PMID- 10941583
TI  - The role of fiberoptic bronchoscopy in airway management of the critically ill
      patient.
AB  - Fiberoptic bronchoscopes (FOB) play a pivotal role in airway management in the
      operating room and critical care environments. This article examines the role of
      FOBs in modern airway management based on a review of recent literature and
      personal experience.

PMID- 10941584
TI  - Augmented fiberoptic intubation.
AB  - Patients who are difficult to intubate are randomly encountered. Patients who are
      in the postoperative period or who have suffered trauma have a greater chance of
      being difficult to intubate. The ability to quickly mobilize trained personnel
      and advanced equipment provides the best chance for a good outcome for these
      patients. Practice in placement of and intubation with LMAs is an important step
      toward providing an extensive safety net for patients needing intubation.

PMID- 10941585
TI  - Transtracheal oxygen delivery.
AB  - Tracheal insufflation of oxygen has at least three major uses for chronic oxygen
      supplementation through a percutaneous catheter, it is an adjunctive measure to
      enhance gas exchange during mechanical ventilation, and it provides an emergency
      therapy for oxygen delivery with upper airway obstruction. In this article the
      mechanisms of gas exchange and techniques of oxygen delivery are described for
      each of these major uses.

PMID- 10941587
TI  - Pediatric airway issues.
AB  - Airway management in the pediatric patient requires an understanding and
      knowledge of the differences and characteristics unique to the child and infant.
      New and exciting techniques are currently being explored and developed for
      management of the pediatric airway. Technology in the area of imaging has allowed
      clinicians to better visualize the airway and aberrations of it. Presently, there
      are many different modes and routes of ventilation and oxygenation that are being
      applied to the pediatric patient for different disease states. Work continues to
      probe for methods and ways that will allow us to take care of infants and
      children better and to provide the safest and most effective means of delivering
      that care. No doubt, there will be more advances and exciting ideas to come that
      lead to better management of the pediatric airway.

PMID- 10941586
TI  - Surgical airway management in the intensive care unit.
AB  - Despite having been a known surgical procedure for over 5000 years, the specifics
      of how, when, and why to perform a surgical airway are still debated. With new
      procedures, equipment, and techniques, operative airway management is becoming
      more complex. New methods of surgical airway management have to be evaluated
      against the gold standard, which will always be the open tracheostomy performed
      in the operating room. Unlike Dr. Jackson in 1909, surgeons today have to
      evaluate these new procedures not only by their efficacy but also by their cost
      effectiveness.

PMID- 10941588
TI  - Airway management in the obstetric patient.
AB  - In summary, the need to manipulate the airway in the pregnant patient requires
      careful consideration and substantial planning. Anatomic and physiologic changes
      of pregnancy, coexisting conditions, and the potential for aspiration all carry a
      risk of morbidity and, indeed, mortality. Preparation, including early and
      repeated airway evaluations throughout pregnancy and labor, is encouraged.
      Knowledge of an emergency airway algorithm and a well thought-out plan for
      difficult intubations are imperative. Equipment must be available and in good
      condition. Finally, proper education and review for individuals involved in the
      delivery of care on the labor floor are mandatory. Although it is not always
      possible to control the manner in which these patients present, it is usually
      possible to control the environment into which they present.

PMID- 10941589
TI  - Teaching airway management skills. How and what to learn and teach.
AB  - It is important to instruct all individuals involved in patient care in airway
      management. The degree of skills actually taught depends on the student.
      Currently, there are many options for teaching. Mannequin training is the one
      best suited to instruct a large number of students in a variety of skills.
      Training of surgical and obstetric residents improves relations, may improve
      patient safety, and educates these individuals regarding the risks of failed
      intubation. Actual clinical decisions regarding patient management are based on
      the airway examination. There is room for improvement in instruction, even in
      anesthesiology programs. Various techniques must be taught and practiced. As more
      anesthesiologists become trained and then train other physicians, the number of
      cases in the Closed Claims Study involving the airway will continue to decrease.

PMID- 10941590
TI  - Organization of personnel and resources for airway management in the hospital and
      office environment.
AB  - Good airway management depends on a system that emphasizes teamwork to expedite
      care and minimize errors. By understanding the accreditation and licensing
      requirements, appropriate personnel and equipment can be allocated along cost
      effective guidelines. Newer techniques for management of the difficult airway,
      such as the laryngeal mask airway (LMA; LMA North America, San Diego, CA) and
      flexible fiberoptic bronchoscope, provide alternatives to the emergency
      cricothyrotomy. A program of continuous quality improvement and clinical
      guidelines will enhance patient care and suggest intelligent use of airway
      resources.

PMID- 10941591
TI  - Otto Lowenstein: neurologic and ophthalmologic testing methods during his
      lifetime.
AB  - Lowenstein's work on the pupil is well known in this country and in Europe. It
      constituted, however, only one of many of his fields of interest. In all of them
      his contributions were based on experiments in which accurate, objective
      recording replaced mere observation with the unaided eye. The resulting traces,
      obtained under stable conditions and with well-defined stimuli, revealed specific
      normal or pathologic reaction patterns, and these, in turn, allowed recognition,
      quantification and localization of the underlying physiologic mechanisms or
      pathologic defects. During the early decades of this century Lowenstein invented
      and built his own instruments. And as more advanced technical means became
      available, he adopted these, so that his methods became more elegant and less
      time-consuming. This history forms an interesting parallel to the development of
      work done by others throughout the twentieth century.

PMID- 10941592
TI  - General Mikhail Kutuzov: one-eyed defender of Moscow.
AB  - General Mikhail Kutuzov was a charismatic Russian general, most remembered for
      his defense of Moscow against Napoleon. He was in and out of favor with the
      emperor, Alexander I, but in times of crisis, on more than one occasion he was
      called back to lead the Russian Forces. From the standpoint of ophthalmology, it
      is of interest that while fighting the Turks, Kutuzov sustained two separate
      severe head wounds that ultimately led to loss of sight in his right eye. A
      portrait of General Kutuzov hangs in the Hermitage Museum in St. Petersburg,
      Russia, Kutuzov's birthplace. In the portrait Kutuzov is standing with his left
      side facing forward, presumably to hide his disfigured right eye. He lost the
      Battle of Austerlitz against Napoleon and at best gained a draw at the Battle of
      Borodino. Nevertheless, the latter battle was the beginning of the end for
      Napoleon's Grand Armee. They entered a deserted Moscow, part of Kutuzov's
      scorched earth policy that left no food or housing for the enemy, and with the
      Russian winter rapidly approaching, Napoleon began his long retreat from Russia.
      As with the German army, the harsh winter claimed many casualties while Kutuzov
      added to the French misery by harassing the retreating army from the rear. Of
      450,000 French soldiers, only 10,000 returned to France.

PMID- 10941593
TI  - Three pioneers in the early history of neuroradiology: the Snyder lecture.
AB  - The early history of neuroradiology is linked to three pioneers who worked during
      the first half of the 20th century. Two were neuropsychiatrists and one was a
      neurosurgeon. Arthur Schuller, a Viennese neuropsychiatrist, was the first to
      study systematically the X-ray skull changes caused by intracranial disease. He
      is generally regarded as the 'father of neuroradiology'. Walter Dandy, the great
      neurosurgeon of Johns Hopkins, introduced ventriculography and
      penumoencephalography. Egas Moniz, a Portuguese neuropsychiatrist, developed
      cerebral angiography, and was awarded the Nobel Prize in Medicine for originating
      prefrontal lobotomy. The work of these three pioneers laid the basis through
      which modern neuroradiology became a separate discipline.

PMID- 10941594
TI  - Alan C. Woods, Sr., M.D. A giant in his time.
AB  - Alan C. Woods, Sr. was born in Baltimore in 1889 and died there in 1963 after
      living a full life. He excelled in ophthalmology and medical school leadership,
      patient care, scientific investigation, promulgation of ideas, clear thinking and
      writing, love of literature and most dramatic of all, he made a life of fun and
      play for his family, friends, colleagues and the ophthalmologists he trained.
      Late in his professional life, 1958, the year he received the Gonin Medal in
      recognition of his work, he made his most important contribution, recognition and
      clarification of the Ocular Histoplasmosis Syndrome.

PMID- 10941595
TI  - Dowager-duchess lorgnettes.

PMID- 10941596
TI  - Emil Gruening.
AB  - Emil Gruening was the first chief of ophthalmology at the Mount Sinai Hospital,
      in New York City. The hospital started in a couple of brownstone tenement
      buildings in lower Manhattan. Some eye patients were cared for there and many
      more after moving to much larger buildings at 66th Street and Lexington Avenue.
      Gruening came to the United States from Posen in Prussia and soon afterwards
      joined the Union army. From Appomattox he returned to New York for completion of
      his medical studies. He went to Europe and studied with such notables as von
      Graefe and Helmholtz. He did cataract surgery with a Graefe knife, with a nurse
      at times holding his beard out of the way. He also did ear, nose, and throat
      surgery. There is a drawing of him doing a mastoid operation on a child with
      Abraham Jacobi, the father of American pediatrics, watching him. While at Mt.
      Sinai, William Wilmer participated in the transplant of a rabbit eye into a
      patient, but went on to achieve greater things in the field. When Gruening died,
      Wilmer wrote that next to his own father he respected Gruening more than any man
      he knew. Emil's son Ernest became Governor of Alaska and Senator from Alaska.
      When Gruening retired the Eye service was jointly run by Charles H. May and Carl
      Koller, but those are other tales to tell.

PMID- 10941597
TI  - The effect of technology on the indications for cataract surgery.
AB  - Before the introduction of modern ophthalmic surgical technology following World
      War II, cataract extraction was easier and safer to perform if the cataract was
      far advanced (mature) and both eyes were involved. The surgeon was constrained
      from early surgery by the frequency of severe complications, the long
      convalescent period, and the distortions of aphakic glasses. Now it is easier to
      perform phacoemulsification and implant lenses in the early stages of cataract
      formation when the nucleus is soft and the posterior lens capsule has not been
      weakened with age. Also, modern small-incision extracapsular cataract extraction
      has a low rate of complications and a short convalescent period. It is feasible
      to extract a clear lens or one with minimal opacifications and have a grateful
      patient. The surgeon is capable of improving the refractive state of the eye by
      selecting the power of the intraocular lens. These facts have led to instances
      where cataracts have been extracted that were responsible for minimal or no
      symptoms.

PMID- 10941598
TI  - The Galezowski tradition in Paris.
AB  - Xavier Galezowski (1832-1907) was born in Poland, received his first MD degree in
      St. Petersburg, Russia, and a second MD degree in Paris. He established an
      important ophthalmologic clinic in Paris, which trained many prominent
      ophthalmologists and treated numerous patients. He published many articles and
      textbooks.

PMID- 10941599
TI  - Synthesis and pharmacological evaluations of N-(substituted benzoylamino)-5
      carbethoxymethyl-1,2,3,6-tetrahydropyridines as potential antiinflammatory
      agents.
AB  - In a continuing effort to enhance antiinflammatory activities, a series of
      1,2,3,6-tetrahydropyridines, 4-tert butyl (9a), 4-methoxy (9b), 2-fluoro (9c), 3
      chloro (9d) and 3,4-dichloro (9e) benzoylamino-5-carbethoxymethyl-1,2,3,6
      tetrahydropyridines, were synthesized and evaluated for their antiinflammatory
      activities. Antiinflammatory activities were screened in animal models employing
      carrageenan induced paw-edema assay on the male Sprague-Dawley rat. Relative
      potencies for carrageenan induced paw-edema assay were 1, 0.07, > 0.03, 0.14, 0.4
      and 0.12 for indomethacin (IC50 = 3 mg/kg), 9a, 9b, 9c, 9d and 9e, respectively.
      These novel tetrahydropyridines were assessed for nonsteroidal antiinflammatory
      drug-mediated inhibition of nitric oxide generation in RAW 264.7 macrophage cell
      line using Griess' reagent. Relative potencies for inhibition of nitric oxide
      generation by macrophages stimulated with lipopolysaccharide (1 microgram/ml)
      were 1, 0.48, 0.44, 0.43, 0.45 and 0.45 for indomethacin (IC50 = 0.434 mM), 9a,
      9b, 9c, 9d and 9e, respectively. The results show that novel tetrahydropyridines
      have moderate antiinflammatory activities and that they inhibit nitric oxide
      production by inhibiting inducible nitric oxide synthase.

PMID- 10941600
TI  - Changes in paraoxonase and apolipoprotein A-I, B, C-III and E in subjects with
      combined familiar hyperlipoproteinemia treated with ciprofibrate.
AB  - The aim of our study was to determine whether, in patients with familiar combined
      hyperlipoproteinemia (FCH), ciprofibrate produces changes in paraoxonase, which
      acts as an antioxidant. A further aim was to estimate changes in serum levels of
      apolipoproteins, especially in apolipoprotein (apo) A-I and apoC-III. One of the
      mechanisms of action of fibrates is the activation apo A-I biosynthesis and the
      inhibition of apoC-III production. It is performed in the liver through
      peroxisome proliferator activated receptor (PPAR)-alpha activity. We found that
      ciprofibrate administration enhanced production of apoA-I and paraoxonase
      transport capacity. Decreases in paraoxonase during ciprofibrate treatment were
      not statistically significant but increases in serum levels of apoA-I were
      statistically significant. Levels of apoC-III were decreased, which suggests that
      ciprofibrate belongs in the group of fibrates that influences lipoprotein
      metabolism through PPAR-alpha activity.

PMID- 10941601
TI  - Antihypertensive and antihyperlipidemic effects of Achillea wilhelmsii.
AB  - Achillea wilhelmsii C. Koch (Asteraceae) is widely found in different parts of
      Iran. This plant is full of flavonoids and sesquiterpene lactones, which have
      been shown to be effective in lowering blood lipids and hypertension. We
      conducted a double-blind placebo controlled clinical trial to study the
      antihyperlipidemic and antihypertensive effects of Achillea drops. We randomly
      selected 120 men and women, aged 40-60 years, and divided them in two distinct
      groups of moderate hyperlipidemic and primary hypertensive subjects. They were
      treated either with hydroalcoholic extract or with placebo in the form of 15-20
      drops twice daily for more than 6 months. Blood pressure and serum lipids (total
      cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol and high
      density lipoprotein (HDL) cholesterol) were measured in the groups for 3 periods
      of 2 months each. The mean and standard deviation of alternations in these
      variables between the group taking placebo and that taking drugs was calculated
      by Student's t-test. The results showed a significant decrease in triglycerides
      after of 2 months while decreases in triglycerides, total cholesterol and LDL
      cholesterol were significant after 4 months. Levels of HDL-cholesterol were
      significantly increased after 6 months' treatment. A significant decrease was
      observed in diastolic and systolic blood pressure after 2 and 6 months,
      respectively (p < 0.05).

PMID- 10941602
TI  - Bifidobacteria and lactobacilli in human health.
AB  - The gastrointestinal microflora is a complex ecological system, normally
      characterized by a flexible equilibrium. The most important role of the
      microflora, from the point of view of the host, is probably to act in
      colonization resistance against exogenous, potentially pathogenic,
      microorganisms. Bifidobacteria and lactobacilli are Gram-positive lactic acid
      producing bacteria constituting a major part of the intestinal microflora in
      humans and other mammals. Administration of antimicrobial agents may cause
      disturbances in the ecological balance of the gastrointestinal microflora with
      several unwanted effects such as colonization by potential pathogens. To maintain
      or reestablish the balance in the flora, supplements of intestinal
      microorganisms, mainly bifidobacteria and lactobacilli, sometimes called
      probiotics, have been successfully used. This article reviews the role of
      bifidobacteria and lactobacilli in human health.

PMID- 10941603
TI  - The comorbidity of eating disorders and personality disorders: a meta-analytic
      review of studies published between 1983 and 1998.
AB  - Comorbid personality disorders in eating disordered patients may seriously affect
      the treatment and course of their illness. Several studies show such a
      comorbidity, though with inconsistent findings. Qualitative reviews attribute
      this to methodological shortcomings, but the qualitative method may itself create
      new shortcomings. To circumvent this, the present, more extensive review applies
      a meta-analytic approach. Using the databases MEDLINE and PSYCHLIT, the 28
      articles published between 1983 and 1998 that presented empirical evidence for an
      eating disorder and personality disorder comorbidity suitable for meta-analysis
      were included. We found a higher proportion of eating disordered patients with
      any personality disorder (average proportion = 0.58) related to comparison groups
      (average proportion = 0.28). Compared with anorexia nervosa patients, a higher
      proportion of patients with bulimia nervosa had a concurrent cluster B
      personality (average proportion = 0.44) and a borderline personality disorder
      (average proportion = 0.31). However, no differences between anorexia nervosa and
      bulimia nervosa patients in proportions of cluster C were found (average
      proportion = 0.45 and 0.44 respectively). Patients with eating disorders and
      patients with bulimia nervosa in particular, should be routinely assessed for a
      concurrent personality disorder using structured clinical interviews. In future
      research, more stringent assessment procedures are highly recommended to address
      the question of causality between eating disorders and personality disorders, and
      how eating disorder symptoms and personality disorder symptoms are related to
      treatment effects.

PMID- 10941604
TI  - Prevalence and gender differences in eating attitudes and physical activity among
      Norwegians.
AB  - The aim of the study was to examine gender differences in self-reported eating
      disorder symptoms in relation to the main reasons for participating in physical
      activity and the amount of weekly training among Norwegian adults. The study
      sample consisted of 3084 persons. Scores were obtained for the Eating Disorder
      Inventory (EDI) and from a self-constructed questionnaire concerning physical
      activity and sociodemographic information. The results showed that women had
      twice the risk for > 40 EDI scores than men (Odds Ratio = 2.45, 95% Confidence
      Interval 1.97-3.05). The main predictors for the weekly amount of physical
      activity were associated with improvement in physical performance. Both sexes
      with > 40 EDI scores participated in activity that resulted in body weight
      reduction and improved physical appearance. The results gave reasons to focus
      further on the narrowing gap between genders concerning eating disorder
      attitudes. The amount of weekly physical activity was not a predictor for high
      EDI scores. The pattern and type of activity may be more important in relation to
      pathological eating attitudes and exercise-related behavior.

PMID- 10941605
TI  - Psychometric development of a multidimensional measure of weight-related
      attitudes and behaviors.
AB  - Most weight control programs facilitate weight loss by encouraging participants
      to adopt healthy eating patterns and increase physical activity. There is a need
      for a relatively brief measure of eating habits and physical activity that could
      be used to evaluate changes in behavior during weight loss treatment. The purpose
      of this series of four studies was to develop and validate such a measure, which
      was subsequently named the Weight Loss Behavior Scale (WLBS). Study 1 (n = 533)
      included item and scale development and examination of the WLBS's factor
      structure and internal consistency. Study 2 (n = 226) evaluated the test-retest
      reliability and convergent validity of its subscales. Study 3 examined their
      reliability and internal consistency scales in a predominantly overweight sample
      (n = 36). Study 4 evaluated the WLBS as a treatment outcome measure in a weight
      loss intervention (n = 50). Study 1 found that the WLBS contained five internally
      consistent and stable factors: 1) Concern with Dieting and Weight, 2) Exercise,
      3) Overeating, 4) Avoidance of Fattening Foods and Sweets, and 5) Emotional
      Eating. Study 2 found convergent validity for the WLBS by assessing the
      correlation of its factors/scales with established inventories of comparable
      constructs, e.g., dietary restraint, disinhibited eating, and physical activity.
      Test-retest reliability of the five scales was also supported in this second
      study. In Study 3, support for the internal consistency and test-retest
      reliability of the WLBS among overweight individuals was found. Study 4 found
      that all scales significantly changed in the expected directions after a 5-month
      behavioral weight loss treatment. The findings from this series of studies
      suggest that the WLBS is a reliable and valid self-report inventory of cognitive
      and behavioral scales associated with weight control that can be utilized as an
      outcome measure for weight loss interventions.

PMID- 10941606
TI  - Prevalence and dimensionality in adolescent eating problems.
AB  - Prevalence of three eating problem dimensions (body concerns, dieting, and loss
      of control over eating) was studied in a Norwegian sample consisting of 4129
      normal adolescents aged 12-16. The existence of eating problem dimensionality had
      been demonstrated in an earlier study of the same sample, and is in line with the
      reasoning presented in both restraint theory and the continuum hypothesis for
      eating disorders. Body concern was the most dominant dimension in both genders in
      the present study, whereas loss of control over eating was the least dominant for
      girls. For boys, both the dieting and the loss of control over eating dimension
      showed a low dominance. Older girls reported significantly more eating problems
      than younger girls, but this difference was not found for boys. The results are
      discussed and taken to support restraint theory and the continuum hypothesis. It
      is concluded that the study gives support to the view of the relationship between
      the three dimensions as cumulative and developmental, and that longitudinal
      research should be conducted to examine how these eating problems are related to
      later eating disorders.

PMID- 10941607
TI  - Night eating syndrome. Preliminary results.
AB  - Clinical aspects of the "night eating syndrome" (NES) are described. Recent
      studies, also referred to in the present report, have revealed certain triggering
      factors of this syndrome, but do not reveal the nature of the relationship
      between awakening and compulsory need for food. According to the psychodynamic
      interpretation, these subjects eat at night to replace dreaming, to which they
      offer strong resistance, whilst according to the psychobiological interpretation,
      motivational stimuli develop the irresistible and repeated desire for food.
      Within a post-rational cognitive theoretical model, the compulsion to food would
      be the mode through which subjects obtain a modified conscious state necessary to
      appease the suffering due to an experience of emptiness and incapacity.
      Psychological support associated with pharmacological treatment (benzodiazepine,
      gamma-hydroxybutyric acid) has been shown, in a personal series, to be effective
      both upon the sleep disorder and craving.

PMID- 10941608
TI  - Weight loss after dieting with behavioral modification for obesity: the
      predicting efficiency of some psychometric data.
AB  - The aim of the study was to identify the predicting efficiency of some
      psychometric data on weight loss after behavior modification in moderately obese
      patients. A group of patients on a weight loss program with a moderately
      hypoenergetic diet plus behavior modification therapy for 24 weeks completed the
      Eating Inventory (EI), the Eating Disorder Inventory (EDI), the Body Shape
      Questionnaire (BSQ) and the Body Attitude Questionnaire (BAQ). Correlations
      between the pre-diet and post-treatment scores were evaluated by stepwise
      regression analysis. The weight loss percentage was positively correlated with
      the EDI Bulimia scale and the BAQ Feeling Fat, and negatively with the EDI Body
      Dissatisfaction and Interpersonal Distrust scores. These findings indicate the
      true effectiveness of the behavior modification technique employed to extinguish
      bulimic behaviors. Furthermore, it can be suggested that realistic attitudes
      towards own fatness with a strong motivation and a good relationship with the
      therapist guarantee a greater weight loss.

PMID- 10941609
TI  - Differences and similarities in the personality structure of 327 women with
      eating disorders.
AB  - The symptomatology of Eating Disorders (ED) varies considerably and it is of
      interest to determine whether one can attribute this to different personality
      structures and hence establish the most effective treatment. The present study
      investigates the psychopathological characteristics of clinical ED subjects
      divided by diagnostic subtypes, age at onset and duration of disorder on
      admission. Three hundred and twenty-seven women were administered the EAT 40 and
      MMPI. One-way ANOVA and Bonferroni post-hoc multiple comparisons were performed
      on subsamples: no significant differences emerged with regard to age at onset and
      duration of ED, whereas the diagnostic subtypes obtained significantly different
      MMPI validity scale scores. These results can be referred to a common core of ED
      represented by cognitive organization and personal meaning.

PMID- 10941610
TI  - Born a hundred years ago.

PMID- 10941611
TI  - Research in reproduction: the Indian scenario in the last decade [I].
AB  - The physiology of reproduction attempts to decipher the biological basis of
      procreation. Fundamental advances in the biology of reproduction are essential to
      decipher this process. In this article, an attempt has been made to chronicle
      some recent advances in our understanding of the biology of reproduction during
      the last decade based on the contributions of scientists working in India.

PMID- 10941612
TI  - Interaction of pentazocine with calcium channel blocking drugs during chemical
      and thermal pain in mice.
AB  - The present study was designed to investigate the antinociceptive interaction of
      a clinically used opioid, pentazocine which produces its analgesic effect mainly
      through kappa receptors, with some calcium channel blockers (CCBs, viz.
      Diltiazem, flunarizine, nimodipine and verapamil--each representing one chemical
      class) in formalin and tail flick tests in mice. All the CCBs, except verapamil,
      significantly inhibited the formalin-induced pain response in a dose-dependent
      manner. However, none of these drugs affected tail flick latency at any of the
      studied doses. Pentazocine showed a significant antinociceptive response in both
      pain models, although a high dose was required to increase the tail flick
      latency. Pretreatment with all CCBs, individually enhanced the analgesic effect
      of pentazocine in both formalin and tail flick tests. In the latter test of
      nociception, a per se ineffective dose of pentazocine, showed a significant
      analgesic response in presence of CCB dose which itself was not effective in the
      test. Chronic concomitant administration of diltiazem with pentazocine did not
      prevent the development of tolerance to the opioid compound. However, diltiazem
      when given in combination with pentazocine to pentazocine-tolerant animals, it
      effectively reversed the tolerance. Results of the study thus suggest that
      concomitant treatment with CCBs, irrespective of their chemical nature, not only
      potentiate the antinociceptive effect of pentazocine in opioid naive animals in
      both tonic and acute nociceptive tests but also reverse the pentazocine
      tolerance.

PMID- 10941613
TI  - Effects of dietary selenium (SE) on morphology of testis and cauda epididymis in
      rats.
AB  - Selenium is an essential micronutrient for animals. To determine whether its
      excess in diet induces morphological changes within the male reproductive system,
      a detailed qualitative and quantitative evaluation of the changes in the
      histology of the testis and cauda epididymis was undertaken in male rats. Adult
      male albino rats were fed 6 and 8 ppm Se in diet for 6 and 9 weeks. Each male
      consuming 6 ppm Se was mated with two untreated females, their offsprings were
      allowed to mature upto 12 weeks of age. The testes and cauda epididymes of male
      rats were prepared for light microscopy. Excess of dietary Se caused dose-time
      dependent reduction in body weight and reproductive organ weights but increase in
      number of morphologically abnormal spermatozoa. Histopathological studies of the
      testes and cauda epididymis have revealed that Se-rich diets cause dose-time
      dependent reduction in tubular diameter, epithelial height, number of
      spermatogenic cells and disintegration of cellular associations in the
      seminiferous tubules of testes along with reduction in the diameter of cauda
      epididymal tubules and pseudostratification of their epithelial lining. Progeny
      (feeding on normal diet) of paternally treated rats has shown retarded growth.

PMID- 10941614
TI  - Prenatal exposure of an alcoholic beverage (Arrack) on fetal lipid metabolism in
      rats.
AB  - The objective of this study was to determine the effects of a country liquor
      (Arrack) and the equivalent quantity of ethanol on liver function and lipid
      metabolism in utero. Female rats of average weight 125 g were exposed to Arrack
      (12 ml/kg body weight/day) and ethanol (3.2 ml/kg body weight/day) for 15 days
      before conception and throughout gestation. On 13th day and 19th day of
      gestation, altered liver function and hyperlipidemia was seen in the fetus of
      both the treated groups. Altered liver function was evidenced by the increased
      activity of alcohol dehydrogenase and glutamic pyruvic transaminase or alanine
      amino transferase (GPT). Hyperlipidemia was caused by increased biosynthesis
      since the incorporation of 14C acetate to lipids and activities of HMG CoA
      reductase and lipogenic enzymes were elevated. Arrack seemed to potentiate the
      toxicity induced by alcohol indicating the role of non ethanolic portion. Hepatic
      functions of the 13th day fetuses were effected to a lesser degree than the 19th
      day hepatic liver.

PMID- 10941615
TI  - Differential effect of a polyherbal formulation-OB-200G in male and female mice
      subjected to forced swim stress.
AB  - The antistress effect of a polyherbal formulation-OB-200G (500 mg/kg. p.o.) was
      studied in both male and female mice subjected to forced swim stress. Fluoxetine
      (10 mg/kg, i.p.) was chosen as standard drug for comparison. Exposure of mice to
      chronic stress regime resulted in decreased body weight in both male and female
      mice, increased sweetened food intake, anxiety, depression and locomotor activity
      in stressed female mice as compared to unstressed control (normal) mice.
      Treatment with OB-200G resulted in a further decrease in body weight, increased
      food intake and locomotor activity in both stressed male and female mice. It also
      reduced immobility time, decreased latency to enter and increased number of
      entries and time spent in mirror chamber in stressed female mice. Administration
      of fluoxetine (10 mg/kg, i.p.) decreased body weight and food intake in both
      stressed male and female mice. Fluoxetine treatment also increased time spent in
      mirror chamber and decreased immobility time in stressed female mice. Thus, like
      fluoxetine, OB-200G decreased body weight and produced antianxiety and
      antidepressant effects in stressed female mice and may prove beneficial in obese
      patients reported to be more susceptible to stress-related psychological
      disorders.

PMID- 10941616
TI  - Effect of N-2-mercaptopropionylglycine in limiting myocardial reperfusion injury
      following 90 minutes of ischemia in dogs.
AB  - Present study was designed to examine the effectiveness of N-2-mercaptopropionyl
      glycine (MPG) on oxygen free radical (OFR) mediated reperfusion injury. Twenty
      dogs underwent 90 min of left anterior descending (LAD) coronary artery occlusion
      followed by 4 h of reperfusion. In control animals (n = 12), 115 ml of saline was
      infused through left atrium at the onset of reperfusion whereas treated animals
      (n = 8) received loading dose of MPG (40 mg/kg) infused through left atrium for 1
      h followed by maintenance dose (25 mg/kg) for remaining 3 hours. Percentage area
      of necrosis vis-a-vis area at risk and percentage necrosis in left ventricular
      mass in MPG treated animals was significantly lower in comparison to control
      animals. Reperfusion in control group increased the lipid peroxidation and
      lowered glutathione (GSH) and superoxide dismutase (SOD) activity. MPG treatment
      significantly lowered the lipid peroxidation whereas GSH and SOD levels in
      necrotic zone were higher than in control. The above results suggest that MPG can
      offer a significant cardioprotection against oxidative stress in canine model.

PMID- 10941617
TI  - Brainstem auditory evoked potential responses in iron-deficient anemic children.
AB  - Iron deficiency is a major health problem in developing countries manifesting not
      only as overt anemia but also involving the CNS resulting in cognitive and
      behavioral deficits. Iron is an important nutrient and essential element involved
      in myelin formation and neurotransmitter synthesis and thus contributes to normal
      neurological activity. Hypomyelination has been reported in iron deficient states
      with possible neural conduction defects. The brainstem auditory evoked potential
      response is used extensively to identify lesions associated with various
      demyelinating diseases and hence has been used in the present study to observe
      the effect of iron deficiency on sensory brain function. A trend of increased
      absolute and interpeak latencies and reduced amplitudes of the waves leading to a
      definite linear correlation between the severity of anemia and the degree of
      neurophysiological deficit suggests a subclinical involvement of the auditory
      pathway in the brainstem of iron deficient children.

PMID- 10941618
TI  - Trend of blood pressure in north Indian children.
AB  - In the summer of 899 School Children (473 boys and 426 girls) aged 6-11 years in
      Aligarh district, Northern part of India were measured of blood pressure, height
      and weight. Systolic, diastolic and mean arterial blood pressure have a strong
      positive correlation with age, height and weight (P < 0.001). There is no
      significant difference in SBP, DBP and MBP among the boys and girls of
      corresponding age. Inspite of sample fluctuation weight has shown a strong
      correlation with blood pressure (P < 0.001) among both sexes in any of the age
      groups.

PMID- 10941619
TI  - Task related changes in contingent negative variation (CNV) response of
      endogenous evoked potentials.
AB  - Contingent negative variation (CNV) is a slow negative cortical potential shift,
      which occurs during a warned foreperiod reaction time paradigm. Most studies of
      evoked potentials have concentrated on components occurring during the first 300
      msec, although there are important and recordable aspects of signal processing
      occurring well beyond 300 msec e.g. late negative slow wave. CNV has proven
      sensitive to a number of psychological variables, none of which can yet be
      singled out as a definitive or exclusive correlate. Changes are expected if
      measured after a rigorous mental exercise. CNV was measured in 20 normal male
      subjects aged between 18 and 20 years. CNV was recorded twice in each subject
      before and after the administration of a mental task. The auditory mental task
      comprised repeating in reverse order string of random digits read out to the
      subject at a uniform speed of 1 per second. The visual mental task comprised
      reading laterally inverted type written text. Each subject had to undergo 2
      sessions in separate sittings. The latency and amplitude of waves N1, P3,
      orientation (O), expectancy (E), CNV, reaction time (RT) were recorded. These
      values recorded before and after the task were compared statistically using
      student's unpaired t-test. The significant latencies recorded before and after
      the auditory task were, N1: 88.00 +/- 11.96 and 100.00 +/- 21.52 msec, P3: 289.00
      +/- 54.85 and 299.00 +/- 52.91 msec, reaction time (RT): 102 +/- 17.05 msec and
      123 +/- 17.5 msec, and in case of visual task, N1: 88 +/- 13.16 msec and 99.00 +/
      16.51 msec, reaction time (RT): 107 +/- 11.74 msec and 127 +/- 13.42 msec
      respectively. All other CNV wave latencies and amplitude changes were
      insignificant. Hence task effects sensory perception as reflected by increased
      latency of the long latency response N1 and the cortical integrative processes
      resulting in increased reaction time.

PMID- 10941620
TI  - 5-fluorouracil (5-FU) induces the formation of giant cells and sloughing of
      seminiferous epithelium in the rat testis.
AB  - The chemotherapeutic agent, 5-fluorouracil (5-FU) has been widely used in the
      treatment of a variety of cancers. Its effect on the testis has not been
      substantially studied. Present study was conducted to evaluate the gonadotoxicity
      of 5-FU in male albino rats. Animals were injected with single dose of 5-FU (10,
      50 and 100 mg/kg, i.p.) and sampled on 1, 3, 15 and 30 day post exposure. Animals
      were anaesthetised, testes were perfusion fixed by Bouin's fluid. Five micron
      thick paraffin sections were stained with haematoxylin and eosin. Slides were
      screened for the incidence of partially and extensively sloughed tubules. Data
      were analysed by Mann Whitney 'U' test. Only 100 mg/kg induced multinucleated
      cells on 3rd day. All doses of 5-FU induced sloughing of the seminiferous
      epithelium. Maximum number of partially sloughed tubules were seen on third day.
      Partial sloughing was not dose dependent except on 15th day. The extensive
      sloughing was dose dependent except on 30th day. The result indicates that all
      the doses of 5-FU tested in this study cause sloughing of epithelium and only 100
      mg/kg induces the formation of giant cells on third day.

PMID- 10941621
TI  - Influence of kinnow juice on the pharmacokinetics of sustained release
      theophylline in healthy male volunteers.
AB  - The effect of kinnow juice on the pharmacokinetics of a single dose of sustained
      release theophylline was investigated in healthy male volunteers. In a two phased
      open cross-over randomized study, ten healthy male volunteers were given
      sustained release theophylline (300 mg) along with 300 ml of water or kinnow
      juice, a routinely used citrus juice in India. Blood samples were collected at
      different time points from 0-48 hours. Plasma was assayed for theophylline by a
      HPLC method and various pharmacokinetic parameters were calculated and compared.
      The theophylline levels were lower at all the time points with kinnow juice co
      administration as compared to water but were significantly so only during the
      absorption phase from 1-4 hours. The values for all the pharmacokinetic
      parameters evaluated were on the lower side with kinnow juice except Tmax which
      was slightly delayed. None of these alterations was found to be significantly
      different. The results indicate that since there is an interference with the
      absorption of the drug, the patients may be advised not to consume kinnow juice
      when taking a slow release theophylline preparation and the monitoring of plasma
      concentrations of theophylline in patients who routinely consume kinnow juice in
      their diet might be helpful in better management of these patients.

PMID- 10941622
TI  - Statistical estimation of height from arm span in north Indian subjects.
AB  - We measured height and arm span of 400 males and 231 female subjects between 16
      83 years of age. Arm span exceeded height in 82.6% subjects. Mean height to arm
      span ratio was 0.9711 and 0.9816 in males and females respectively, and was not
      significantly correlated with age. Linear regression equations were generated for
      both sexes for prediction of height from arm span and age. The use of height to
      arm span ratio was found to be a less suitable method than the use of regression
      equations in estimating height from arm span.

PMID- 10941623
TI  - Nitric oxide level in children with pulmonary hypertension.
AB  - Nitric oxide is a gas and free radical, which modulates pulmonary and vascular
      tone. Pulmonary vascular endothelial cell produce the nitric oxide. To define the
      relation between nitric oxide and hemodynamic parameters in children with
      pulmonary hypertension, we measured the nitric oxide concentrations of the right
      atrium, right ventricle, pulmonary artery, left ventricle and aorta in 40
      patients during cardiac catheterizations. Patients were divided into two groups
      according to their pulmonary arterial pressure. In group I, the mean pulmonary
      arterial pressure was higher than 25 mmHg and in group II, lower than 25 mmHg.
      Pulmonary nitric oxide level in group I was significantly lower than group II (P
      < 0.05). The right ventricle and mean pulmonary arterial pressures, pulmonary
      vascular resistance and pulmonary flow/systemic flow of the patients in group I
      were significantly higher than those of group II (P < 0.05). In conclusion, we
      found low nitric oxide levels in patients with pulmonary hypertension and
      congenital heart defects.

PMID- 10941624
TI  - The effect of moderate swimming exercise on antioxidant enzymes and lipid
      peroxidation levels in children.
AB  - Strenuous exercise is characterized by increased oxygen consumption and the
      disturbance between intracellular pro-oxidant and antioxidant homeostasis.
      Although there are several studies related to an increase in antioxidant enzyme
      activity in adults doing exercise, the effect of regular exercise on antioxidant
      enzymes and lipid peroxidation levels has not been examined in children. In our
      study, the effects of a four week regular swimming exercise on antioxidant
      enzymes (superoxide dismutase and glutathione peroxidase) activities in
      erythrocytes and plasma thiobarbituric acid reactive substances (TBARS) levels,
      an indicator of lipid peroxidation, were investigated in previously untrained
      healthy children. We found that superoxide dismutase (SOD) activity was increased
      significantly following a four week swimming course (from 581.1 +/- 146.2 to
      791.1 +/- 221.9 U/gHb, P < 0.01). Conversly, plasma TBARS levels were decreased
      from 1.1 +/- 0.4 to 0.9 +/- 0.3 nmol/ml (P < 0.05). Glutathione peroxidase (GPx)
      activity appeared to increase following swimming course, albeit not statistically
      significant (from 45.5 +/- 16.5 to 50.3 +/- 14.8 U/gHb). According to these
      findings, regular swimming exercise has beneficial effects on antioxidant defence
      in healthy children.

PMID- 10941625
TI  - Effect of acute and chronic administration of L-arginine on morphine induced
      inhibition of gastrointestinal motility.
AB  - Effect of acute and chronic administration of L-arginine on morphine induced
      gastrointestinal inhibition was tested in rats. In the test for acute effect, L
      arginine (200 mg/kg, i.v.) was given 10 minutes before the charcoal meal test. In
      the test for chronic effects, L-arginine (200 mg/kg, i.v.) was given twice a day
      for 4 days. Charcoal meal test was done on the fifth day. Morphine was
      administered 45 minutes before the charcoal meal test. Results showed that acute
      administration of L-arginine did not affect the morphine's action on the GIT. In
      contrast, chronic administration of L-arginine reversed the morphine induced
      decrease in gastrointestinal motility. The reversal was however, not complete.
      This data suggests that inhibition of NO may be one of the mechanism of morphine
      induced constipation.

PMID- 10941626
TI  - Antiulcer activity and the mechanism of action of magaldrate in gastric
      ulceration models of rat.
AB  - The present study was undertaken to investigate the mechanism of cytoprotective
      effects of magaldrate in aspirin plus pylorus-ligation model and ethanol-induced
      gastric ulcer model in rats. Magaldrate (60 mg/kg, p.o.) produced a significant
      reduction in the ulcer index and significant increase in mucus content in ethanol
      induced gastric ulceration in rats. In aspirin plus pylorus-ligation model
      magaldrate produced significant decrease in ulcer index, total acidity and
      protein content (PR). It did not produce any significant change in volume of
      gastric secretion. However, it produced significant increase in total
      carbohydrate (TC) level but not in ratio between TC and proteins. It also
      produced a significant decrease in lipid peroxidation (as expressed by
      thiobarbituric acid reactive substance). Our data suggests the cytoprotective
      action of magaldrate on gastric mucosal cells which may be due to protection of
      gastric mucosa from lipid peroxidation.

PMID- 10941627
TI  - Effect of the 5-HT3 receptor antagonist ondansetron on amphetamine-induced
      hyperactivity and stereotypy in rats.
AB  - The effects of different doses of ondansetron (0.1, 0.5, 1, 2 mg/kg) administered
      intra-peritoneally were studied on amphetamine-induced hyperactivity and
      stereotypy in wistar rats. Ondansetron was administered 30 minutes prior to d
      amphetamine (3 mg/kg, i.p.). Ondansetron in doses of 0.5 and 1 mg/kg
      significantly decreased the mean number of head dippings and crossings in the
      hole board test and in doses of 0.1 and 0.5 mg/kg significantly decreased the
      average stereotypic score. Since the hyperactivity and stereotypy are dopamine
      mediated, the effect of ondansetron to reduce these states suggests a potential
      role for ondansetron in conditions with dopamine excess.

PMID- 10941628
TI  - Bone changes during simulated weightlessness in rats.
AB  - Weightless environment due to prolonged Space mission results in decreased
      mineralisation of the weight bearing bones. Hind limb unweighting (HU) in rats by
      tail suspension was used to simulate the effect of weightlessness on tibia. Adult
      male albino rats were divided into two groups as (i) Control (CON, n = 12) and
      (ii) HU for 15 days (HU, n = 18). After 15 days of HU tibia from all the animals
      were removed and subsequently dried and ashed. The calcium content of these bones
      were then determined. HU resulted in atrophic changes in the weight bearing bone,
      tibia, due to the reductions of water content (-35.8%), organic matrix (-12.2%)
      and calcium content (-33.4%). The reduction in the dry wt of tibia (-13.5%) was
      due to proportionate reductions in the organic matrix and total mineral content
      of the bone. The reduction in the mineral content was solely due to the reduction
      in calcium content of the bone.

PMID- 10941629
TI  - Therapy of acanthamoeba keratitis--an experimental study.
AB  - The study was conducted to determine the efficacy of various drugs/agents in the
      treatment of experimentally induced Acanthamoeba Keratitis (A. keratitis). Thirty
      rabbits were divided into 5 equal treatment groups and polyhexamethylene
      biguanide (PHMB) 0.02%, fluconazole 0.2%, povidone iodine 5%, aprotinin 40 IU/ml
      and normal saline were administered in a double blind manner, at a dose of one
      drop, 5 times/day. Neomycin 1700 U/ml was used as a common drug in all groups,
      with same frequency. Post therapy subsidence of lid oedema, mucopurulent
      discharge, conjunctival congestion, corneal epithelial defect and anterior
      chamber reactions were noted. Average healing time in days (Mean +/- S.D.) were
      13.67 +/- 1.21, 22 +/- 1.41, 23.5 +/- 1.05, 17.0 +/- 1.41 and 28.0 +/- 1.90 for
      PHMB, fluconazole, povidone iodine, aprotinin and normal saline respectively. Lid
      oedema, mucopurulent discharge and conjunctival congestion improved faster in
      PHMB and aprotinin treated eyes. The results of this study suggest that PHMB is a
      better drug for A. keratitis, while aprotinin may be used as an adjuvant drug in
      the management of A. keratitis.

PMID- 10941630
TI  - Polyamines in relation to human benign breast rectal ovarian and endometrial
      tumour.

PMID- 10941631
TI  - PEFR in cement pipe factory workers in relation to smoking.

PMID- 10941632
TI  - Dose of hemodialysis and survival: can we trust important outcomes to a flawed
      measure?

PMID- 10941633
TI  - Membrane distillation of human plasma ultrafiltrate and its theoretical
      applications to haemodialysis techniques.
AB  - Membrane Distillation (MD) is a technique that allows the extraction of water
      from aqueous solutions. The basic principle is that vapour, but not liquid water,
      can pass through hydrophobic micro-porous membranes, along a temperature
      gradient, with consequent separation of water from solutes. In this study we
      evaluated the possibility to utilise MD to extract water from Plasma
      Ultrafiltrate (PU) of patients with Chronic Renal Failure (CRF). The experiments
      were carried out in vitro by a hydro-phobic polypropylene hollow-fibre
      distillation module; PU was obtained by a CRF patient utilising a high
      permeability polisulphone membrane. The results show that water can be extracted
      by MD from PU of CRF subjects at a constant rate and that none of the substances
      analysed in PU was able to pass through the polypropilene membrane. In the future
      MD could integrate extra-corporeal blood purification techniques allowing the re
      utilisation of plasmatic water thus ameliorating the treatment of uraemia.

PMID- 10941634
TI  - Comparison of the quality of life in hemodialysed (HD) and peritoneally dialysed
      (CAPD) patients using the EORTC QLQ-C30 questionnaire.
AB  - BACKGROUND: The aim of the paper was to assess reliability and validity of the
      QLQ-C30 questionnaire in studying the quality of life in dialysed patients, and
      then to compare the life quality in patients on hemodialysis (HD), continuous
      ambulatory peritoneal dialysis (CAPD) and healthy controls. The present study
      included 65 HD patients, 22 CAPD patients and a group of 76 healthy volunteers.
      METHODS: Quality of Life Questionnaire (QLQ-C30), Hospital Anxiety and Depression
      Scale (HADS), Cantrill ladder. RESULTS: The EORTC QLQ-C30 questionnaire appeared
      to be a reliable and valid tool for assessing the quality of life in dialysis
      patients. HD patients had significantly poorer quality of life in the areas of
      physical, social, cognitive and emotional functioning in comparisons to the
      controls. CAPD patients were not significantly different life quality-wise from
      controls, except for their social and professional life.

PMID- 10941635
TI  - In vitro and in vivo uric acid lowering by artificial cells containing
      microencapsulated genetically engineered E. coli DH5 cells.
AB  - Increase in systemic uric acid occurs in renal insufficiency, gout, chemotherapy,
      and other diseases. Dialysis can lower this metabolite but is expensive. The use
      of drugs can, sometime, result in side effects. Therefore, a suitable affordable
      method for this is required. In this article, for the first time, we report the
      use of artificial cells containing micro encapsulated genetically engineered E.
      Coli DH5 cells for lowering uric acid in vitro and in vivo. Results show that
      this novel approach has the ability to significantly lower uric acid from 84.80
      +/- 3.40 mg/dl to 9.32 +/- 0.05 mg/dl in vitro and from the plasma of the
      experimental animals from the control levels of 71.00 +/- 27.49 mg/dl to 20.33 +/
      17.92 mg/dl in vivo. Continued daily oral administration maintained the plasma
      uric acid concentration of experimental uremic rats to the normal plasma uric
      acid level range during the entire test period.

PMID- 10941637
TI  - Origin and appearance of HITS induced by prosthetic heart valves: an in vitro
      study.
AB  - Patients with mechanical heart valve prostheses show significantly enhanced
      numbers of HITS detected by transcranial Doppler ultrasound. In order to assess
      the origin of HITS formation, an in vitro study was set out to quantify valve
      induced microemboli for mechanical and bioprosthetic valves under various
      circulatory conditions by means of Ultrasound-Doppler-Sonography. At the same
      time the influence of CO2 partial pressure on HITS rate vas investigated. It can
      be summarised that for mechanical heart valve prostheses a strong correlation
      exists between left ventricular dp/dtmax and the detected HITS rates. It was also
      demonstrated that a bioprosthesis generates significantly less HITS than a
      mechanical valve. The origin of HITS is gaseous since the tests were carried out
      using a cell-free filtered water-glycerol test fluid. The HITS rate could be
      increased by increasing the amount of dissolved gas within the test fluid. The
      results support the hypothesis that cavitation is the key factor in the
      appearance of gaseous microemboli at heart valve prostheses.

PMID- 10941636
TI  - Vasoconstrictive eicosanoid responses to extracorporeal circulation with or
      without an oxygenator in fetal lambs.
AB  - INTRODUCTION: This study measured levels of vasoconstrictive eicosanoids during
      ovine fetal cardiac bypass and compared the measurements between two groups: (1)
      a group in which the placenta functioned as the only source of oxygen supply
      during the bypass (the placenta group), and (2) a group in which an artificial
      oxygenator, instead of the placenta, was included in the bypass circuit (the
      oxygenator group). MATERIALS AND METHODS: A total of 16 fetal lambs were randomly
      assigned into either the oxygenator group or the placenta group. Following
      anesthesia, the fetal cardiac bypass procedure was performed. The placenta group
      used a centrifugal pump as the pumping device without an oxygenator during the
      bypass. The bypass circuit in the oxygenator group consisted of a roller pump and
      a membrane oxygenator. The fetal cardiac bypass procedure was performed for 30
      minutes at normothermia in both groups. For the measurements of thromboxane
      B2(TXB2) and prostaglandin E2 (PGE2), blood samples were taken before the bypass,
      at 5 minutes, 15 minutes, and 30 minutes after the start of cardiac bypass, and
      at 15 minutes after weaning from the bypass. TXB2 and PGE2 levels were determined
      by radioimmunoassay with PGE2(125I) and TXB2(125I) assay systems. Hemodynamic
      observations and arterial blood gas analyses were done every 10 minutes. RESULTS:
      The mean arterial pressure and heart rate ranged from 69.8 to 82.6 mmHg and 169
      to 182/min during the bypass in the oxygenator group, and from 14.4 to 44.7 mmHg
      and 64.3 to 75/min in the placenta group. Arterial blood gas analysis showed
      severe hypercapnia and hypoxemia with acidosis during and after the bypass in the
      placenta group. Bypass flow rates were maintained at 140.3-164.0 ml/kg/min in the
      oxygenator group, while flow rates were suboptimal (74.3-97.0 ml/kg/min) in the
      placenta group. There were no statistically significant differences in PGE2
      concentrations before, during, or after bypass, although the placenta group
      displayed a tendency to higher measurements during bypass, compared to the
      oxygenator group. The placenta group also showed higher TXB2 measurements than
      the oxygenator group during the bypass (p = 0.0457). CONCLUSIONS: We have
      demonstrated increase measurements of PGE2 and TXB2 in the placenta group when
      compared with the oxygenator group in an ovine fetal cardiac bypass model,
      although the PGE2 difference failed to reach statistical significance.

PMID- 10941638
TI  - Conditions required for a hybrid artificial liver support system using a
      PUF/hepatocyte-spheroid packed-bed module and it's use in dogs with liver
      failure.
AB  - We studied the effects of a hybrid artificial liver support system we developed
      on dogs with hepatic failure. The system consisted of a multi-channel
      polyurethane foam packed-bed culture module, including primary dog hepatocyte
      spheroids. Blood ammonia was well metabolized by 20 g hepatocytes, but the other
      functions such as glucose concentration, total bile acid concentration, and
      survival time required 30 g hepatocytes to improve conditions. We found that we
      should use a culture substratum that easily forms spheroids, and that an
      artificial liver module should be used as soon as possible after spheroid
      formation by hepatocytes in the module.

PMID- 10941639
TI  - A single institution's experience (1982-1999) with plasma-exchange therapy in
      patients with fulminant hepatic failure.
AB  - Fulminant hepatic failure is a rare, but often fatal complication of acute viral
      hepatitis. This condition, in absence of orthotopic liver transplantation (OLTx)
      surgery, is associated with a high mortality rate, despite the improvement of
      general intensive care. Plasma-exchange (PEx) therapy has been long used to treat
      FHF, in particular by removing toxic substances and correcting the severe
      coagulopathy. In this study we describe our experience with PEx treatment of FHF,
      beginning in 1982. Seventy patients affected with FHF due to various causes (HBV
      = 40; cryptogenic/non-A, non-E = 15; Amanita phalloides = 8; other = 7) were
      treated with PEx (altogether 348 sessions). Overall survival rate, comprising
      patients undergoing OLTx, was 51%, a little higher than what we observed in
      patients (N = 49) treated solely by PEx, i.e., 41%. The best outcome predictor
      was FHF aetiology, owing to the good survival rate in patients with Amanita
      phalloides intoxication and the very poor prognosis of patients suffering from
      cryptogenic/non-A, non-E FHF. Moreover, the marked increase in prothrombin time
      and alpha-fetoprotein levels after 48 hours from admission was associated with a
      good prognosis, whereas the patient's age and coma grade were not clearly
      predictive of survival. Additionally, lymphocyte subpopulation, resulting in a
      CD4/CD8 ratio lower than 1.0 along with CD8 activation with HLA-DR strong
      expression, were associated with a high rate of mortality and morbidity. Our data
      indicate that PEx therapy can improve survival in patients with sufficient
      residual capacity of liver regeneration. Moreover, the identification of certain
      prognostic factors may be useful for the rational planning of therapeutic
      strategy in FHF.

PMID- 10941640
TI  - Design and in vitro testing of a voice-producing element for laryngectomized
      patients.
AB  - A voice-producing element has been developed to improve speech quality after
      laryngectomy. The design process started with the formulation of a list of
      requirements. The lip principle has the best potential for fulfilling the
      requirements. A numerical model was made to find the optimal geometry of an
      element based on the lip principle. Extensive in vitro tests were performed to
      check all requirements. For this a test set-up with realistic acoustic and
      aerodynamic properties was developed. Results show that the protruding lip length
      dominates fundamental frequency, cross-sectional area dominates flow resistance
      and relation between flow and fundamental frequency. Most requirements have been
      fulfilled; both for males and females a potentially good functioning prototype
      could be selected. Clinical experiments will be performed to confirm the quality
      of the voice-producing prosthesis.

PMID- 10941641
TI  - Optics of refractive surgery.

PMID- 10941642
TI  - Market trends in refractive surgery.

PMID- 10941643
TI  - Comanagement of refractive surgery.

PMID- 10941644
TI  - Managing patient expectations.

PMID- 10941645
TI  - Photorefractive keratectomy.
AB  - In this chapter, we have reviewed important aspects of PRK. A thorough
      understanding of the preoperative assessments, techniques, and postoperative
      management is essential to achieve satisfactory visual outcomes. Laser safety
      checks are mandatory. A well-functioning excimer laser with good optics is
      required. The surgeon must avoid any decentration or global tilt. All aspects of
      the technique must be performed with attention to detail. The postoperative
      management requires frequent follow-up visits and psychological reinforcement of
      a healing process that is not instantaneous. PRK is a procedure in evolution.
      Although the results today are impressive, the complications in the future will
      continue to decrease with changes in lasers, techniques, and pharmacological
      management.

PMID- 10941646
TI  - Microkeratomes.

PMID- 10941647
TI  - LASIK complications.

PMID- 10941648
TI  - Diffuse lamellar keratitis: identification and management.

PMID- 10941649
TI  - Management of flap striae.
AB  - There have been no comprehensive investigations of striae after LASIK. The
      ophthalmic literature has few reports, and no one consistent therapy has been
      recommended. Striae are relatively uncommon; nevertheless, refractive surgeons
      need a systematic approach in prevention and therapy for striae. Careful flap
      handling and positioning can prevent many striae. Early recognition is very
      important and makes treatment significantly more likely to eliminate or reduce
      the striae. If the striae are identified within 24 hours, lifting and refloating
      will likely result in resolution of the striae. If the striae are more imbedded
      and have been present longer, additional techniques, such as those discussed, are
      helpful. New techniques will likely be developed because of an increase in
      lamellar procedures and an increase in the occurrence of striae.

PMID- 10941650
TI  - Central islands and decentered ablations after LASIK.

PMID- 10941651
TI  - LASIK enhancements.
AB  - As the field of refractive surgery continues to evolve, an increasing number of
      surgical options are available for LASIK enhancements. Nonetheless, older methods
      such as AK continue to play an important role in enhancement procedures.
      Improvements in instruments and techniques allow for previously made LASIK flaps
      to be safely lifted for additional myopic or hyperopic ablations. Newer methods
      such as Intacs placement provide an effective option for patients who are not
      good candidates for further ablative procedures. These advancements allow
      refractive surgeons to treat a wider range of myopia, hyperopia, and astigmatism
      effectively in eyes with a history of LASIK surgery.

PMID- 10941652
TI  - LASIK after penetrating keratoplasty.

PMID- 10941653
TI  - Laser-assisted in situ keratomileusis for correction of secondary hyperopia after
      radial keratotomy.

PMID- 10941654
TI  - Bioptics.

PMID- 10941655
TI  - TopoLink LASIK.

PMID- 10941656
TI  - Refractive surgery for hyperopia.

PMID- 10941657
TI  - Hyperion laser thermokeratoplasty for hyperopia.

PMID- 10941658
TI  - Astigmatism management.

PMID- 10941659
TI  - Intacs: the intrastromal corneal ring.

PMID- 10941660
TI  - Phakic iris claw artisan intraocular lens for correction of high myopia and
      hyperopia.

PMID- 10941661
TI  - Intraocular phakic implants in the anterior chamber.

PMID- 10941662
TI  - The STAAR posterior chamber phakic intraocular lens.

PMID- 10941663
TI  - The AMO array foldable silicone multifocal intraocular lens.

PMID- 10941664
TI  - Fifty years of solid-phase extraction in water analysis--historical development
      and overview.
AB  - The use of an appropriate sample handling technique is a must in an analysis of
      organic micropollutants in water. The efforts to use a solid phase for the
      recovery of analytes from a water matrix prior to their detection have a long
      history. Since the first experimental trials using activated carbon filters that
      were performed 50 years ago, solid-phase extraction (SPE) has become an
      established sample preparation technique. The initial experimental applications
      of SPE resulted in widespread use of this technique in current water analysis and
      also to adoption of SPE into standardized analytical methods. During the decades
      of its evolution, chromatographers became aware of the advantages of SPE and,
      despite many innovations that appeared in the last decade, new SPE developments
      are still expected in the future. A brief overview of 50 years of the history of
      the use of SPE in organic trace analysis of water is given in presented paper.

PMID- 10941665
TI  - Contributions of theory to method development in solid-phase extraction.
AB  - The kinetic and retention properties of solid-phase extraction devices are
      reviewed from the perspective of method development strategies. Models based on
      frontal analysis are used to correct retention properties of solid-phase
      extraction devices to account for the fact that too few theoretical plates are
      provided for retention to be independent of kinetic factors. The available
      pressure drop for the sampling device largely dictates the choice of useful
      particle sizes and maximum bed length. The use of octanol--water partition
      coefficients and extrapolated values of the retention factor obtained by liquid
      chromatography are poor empirical models for the estimation of breakthrough
      volumes with water as the sample solvent. The solvation parameter model provides
      an adequate description of sorbent retention for the estimation of breakthrough
      volumes, rinse solvent volume and composition, and elution solvent volume and
      composition. Combining the frontal analysis and solvation parameter models offers
      a comprehensive approach to computer-aided method development in solid-phase
      extraction. This is the first step in the development of a structure-driven
      approach to method development in solid-phase extraction that should be more
      reliable and less tedious than traditional trial and error approaches.

PMID- 10941666
TI  - Investigation into the effects of temperature and stirring rate on the solid
      phase extraction of diuron from water using a C18 extraction disk.
AB  - A novel experimental method for determining the equilibrium constant, Keq, and
      the uptake rate constant, kup, for the solid-phase extraction (SPE) of diuron
      from water using a C18 Empore extraction disk is reported. Log Keq and log kup
      are determined at 7.0, 11.0, 18.0 and 23.0 degrees C and for stirring rates of
      100, 200 and 400 rpm. From a Van 't Hoff plot of log Keq versus T-1 the enthalpy
      of sorption, delta H0, is shown to be negative which indicates that the
      thermodynamic process of uptake is exothermic. The rate of stirring has no effect
      on log Keq over the temperature range 7.0-23.0 degrees C. The enthalpy of
      activation, delta H0, calculated from Arrhenius plots of log kup versus T-1 at
      100, 200 and 400 rpm show that the kinetic process of uptake is endothermic. At
      100 rpm the rate of uptake is limited by the aqueous diffusion of diuron. At 200
      rpm or greater the aqueous diffusion layer around the disk is sufficiently small
      to prevent diffusion from being a limiting factor. The method described in this
      paper is limited to the analysis of analytes that contain a significant UV
      chromophore and are relatively soluble in water, but it can also be used to
      investigate pH and salinity effects on the SPE of diuron from water.

PMID- 10941667
TI  - Recent developments in polymer-based sorbents for solid-phase extraction.
AB  - A review with 136 references on the principles and recent developments in the
      solid-phase extraction based on polymer sorbents is presented. New polymer-based
      materials, chromatographic modes, experimental configurations are described and
      their advantages for a rapid sample preparation of certain classes of compounds
      with different functional groups are discussed and compared to silica-based
      sorbents.

PMID- 10941668
TI  - Graphitized carbons for solid-phase extraction.
AB  - The objective of this review is to provide updated information about the most
      important features of graphitized carbonaceous sorbents used for solid-phase
      extraction (SPE) of organic compounds from liquid natural matrices or extracts.
      The surface characteristics of graphitized carbon blacks and porous graphitic
      carbons are described which are responsible for the various types interactions
      (hydrophobic, electronic and ion-exchange) with analytes. The method development
      is given which is based on the prediction from liquid chromatographic retention
      data obtained using porous graphitic carbon. Emphasis is placed on their
      capability for trapping very polar and water-soluble analytes from aqueous
      samples. Comparison is made between carbon-based SPE sorbents and other reversed
      phase materials such as octadecyl silicas and highly cross-linked copolymers.
      Especially, the difficulty encountered for the desorption of some strongly
      retained analytes is explained by LC data and solutions are given for optimizing
      the composition and volume of the desorption solution. Many examples illustrate
      the various common features of graphitized carbons which are the extraction of
      very polar analytes and multiresidue extractions. Some applications are specific
      to graphitized carbon black due to the presence of surface functional groups.
      They include the extraction of anionic compounds such as benzene and naphthalene
      sulfonates or acidic pesticides. Other applications are specific to porous
      graphitic carbon due to its flat and homogeneous surface. One example is the
      trace extraction of coplanar polychlorinated biphenyls (PCBs), dibenzo-p-dioxins
      and dibenzofurans from other PCB congeners.

PMID- 10941669
TI  - Automating solid-phase extraction: current aspects and future prospects.
AB  - This paper reviews current trends and techniques in automated solid-phase
      extraction. The area has shown a dramatic growth the number of manuscripts
      published over the last 10 years, including applications in environmental
      science, food science, clinical chemistry, pharmaceutical bioanalysis, forensics,
      analytical biochemistry and organic synthesis. This dramatic increase of more
      that 100% per year can be attributed to the commercial availability of higher
      throughput 96-well workstations and extraction plates that allow numerous samples
      to be processed simultaneously. These so-called parallel-processing workstations
      represent the highest throughput systems currently available. The advantages and
      limitations of other types of systems, including discrete column systems and on
      line solid-phase extraction are also discussed. Discussions of how automated
      solid-phase extractions can be developed, generic approaches to automated solid
      phase extraction, and three noteworthy examples of automated extractions are
      given. The last part of the review suggests possible near- and long-term
      directions of automated solid-phase extraction.

PMID- 10941670
TI  - Matrix solid-phase dispersion.
AB  - Matrix solid-phase dispersion (MSPD) is a patented process, first reported in
      1989, for conducting simultaneous disruption and extraction of solid and semi
      solid samples. MSPD permits complete fractionation of the sample matrix
      components as well as the ability to selectively elute a single compound or
      several classes of compounds from the same sample. The method has been applied to
      the isolation of drugs in food animal tissues but has also found wide application
      in the analysis of herbicides, pesticides and pollutants from animal tissues,
      fruits, vegetables and other matrices. The present article provides a review of
      MSPD applications in these and related fields and discusses the factors known to
      affect MSPD methods. Both the practical and theoretical aspects of MSPD are also
      presented.

PMID- 10941671
TI  - Sorbent trapping of volatile organic compounds from air.
AB  - The use of sorbents in trapping volatile organic compounds in air for subsequent
      analysis is reviewed. Sorbents are classified in accordance with the mechanism
      used to recover the trapped compounds, either solvent or thermal desorption. The
      use of sorbents is contrasted with other sampling procedures, such as collecting
      whole air samples using canisters. New developments such as solid-phase
      microextraction are described. In particular, emphasis is placed on a holistic
      approach to sampling and analysis, and communication is encouraged between those
      who take samples in the field, and those who perform the analysis.

PMID- 10941672
TI  - Evolution of solid-phase microextraction technology.
AB  - The main objective of this contribution is to describe the development of the
      concepts, techniques and devices associated with solid-phase microextraction, as
      a response to the evolution of understanding of the fundamental principles behind
      this technique. The discussion begins with an historical perspective on the very
      early work conduced almost a decade ago. As new fundamental understanding about
      the functioning of the technology developed, new ways of constructing and using
      the SPME devices evolved.

PMID- 10941673
TI  - Solid-phase extraction for multiresidue analysis of organic contaminants in
      water.
AB  - To overcome the limitations of the detection systems associated with gas or
      liquid chromatography, a sample pretreatment is required with the objective to
      provide a sample fraction enriched with all the target analytes and as free as
      possible from other matrix components. There is now no doubt that solid-phase
      extraction (SPE) has now become the method of choice for carrying out
      simultaneously the extraction and concentration of many compounds in aqueous
      samples. Many recent applications of SPE to multiresidue analysis are reviewed
      with an emphasis on the importance of the choice of the sorbent and of the sample
      volume. SPE is particularly well adapted to multiresidue analysis including
      compounds from a wide range of polarity or characterized by various physico
      chemical properties. However, SPE is not completely free from practical problems
      inherent to the nature of the compounds or to the coupling to the chromatographic
      systems. Many examples are reported to illustrate these problems which can in
      most cases be circumvented. New developments in SPE are also reviewed.

PMID- 10941674
TI  - Multiresidue methods using solid-phase extraction techniques for monitoring
      priority pesticides, including triazines and degradation products, in ground and
      surface waters.
AB  - The review describes the use of solid-phase extraction (SPE) techniques for
      monitoring priority pesticides in ground and surface waters. The focus is on
      triazine herbicides and their degradation products. Data concerning the fate,
      occurrence, properties and extraction of triazines and their degradation products
      using different SPE techniques are tabulated and discussed.

PMID- 10941675
TI  - Solid-phase extraction of acidic herbicides.
AB  - A discussion of solid-phase extraction method development for acidic herbicides
      is presented that reviews sample matrix modification, extraction sorbent
      selection, derivatization procedures for gas chromatographic analysis, and clean
      up procedures for high-performance liquid chromatographic analysis. Acidic
      herbicides are families of compounds that include derivatives of phenol (dinoseb,
      dinoterb and pentachlorophenol), benzoic acid (acifluorfen, chloramben, dicamba,
      3,5-dichlorobenzoic acid and dacthal--a dibenzoic acid derivative), acetic acid
      [2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid
      (MCPA) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)], propanoic acid
      [dichlorprop, fluazifop, haloxyfop, 2-(4-chloro-2-methylphenoxy)propanoic acid
      (MCPP) and silvex], butanoic acid [4-(2,4-dichlorophenoxy)butanoic acid (2,4-DB)
      and 4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB)], and other miscellaneous
      acids such as pyridinecarboxylic acid (picloram) and thiadiazine dioxide
      (bentazon).

PMID- 10941677
TI  - Solid-phase extraction of polycyclic aromatic compounds.
AB  - Solid-phase extraction (SPE) for two groups of polyaromatic compounds--polycyclic
      aromatic hydrocarbons and naphthalenesulfonates--with completely different
      problems in the extraction process are reviewed. The sorbents used in each case
      and the different steps of SPE are studied. Particular problems encountered in
      the SPE of each group are described. Adsorption problems of PAHs which require an
      organic solvent or a surfactant to be added to the sample are explained. The need
      of ion-pair solid-phase extraction for extracting naphthalenesulfonates and the
      influence of the inorganic species in the extraction are discussed. The on-line
      systems are described for both group of compounds.

PMID- 10941676
TI  - Solid-phase extraction of quaternary ammonium herbicides.
AB  - This paper highlights recent advances in the solid-phase extraction (SPE) of
      quaternary ammonium herbicides in water, soil, plant and biological samples.
      After a brief introduction summarizing the properties of quaternary ammonium
      herbicides and the difficulties involved in measuring them, attention is paid
      primarily to solid supports used for isolation and concentration, pre-treatments
      required for the different matrices, and eluents applied for quantitative
      desorption of these analytes. The determination techniques used after SPE and
      applications of the proposed SPE methodology are also briefly discussed.

PMID- 10941678
TI  - Solid-phase extraction of phenols.
AB  - Sample preparation for phenol analysis using solid-phase extraction (SPE) is
      reviewed. The scope of the review has been restricted to the literature dealing
      with the analysis of phenols as the main objective. The use, advantages and
      disadvantages of silica sorbents, polymeric, functionalized, carbon-based and
      mixed available sorbents, when applied to the separation and preconcentration of
      phenols, as well as the available experimental devices, are discussed. Other
      aspects such as phenol derivatisation prior to SPE, solid-phase microextraction,
      matrix effects and the storage of phenols in SPE cartridges, have been also
      discussed.

PMID- 10941679
TI  - Solid-phase extraction for combinatorial libraries.
AB  - Solid-phase extraction (SPE) has during the last three years emerged as a
      convenient method for the purification of compound libraries prepared by solution
      synthesis. The widespread use of SPE in combinatorial chemistry can be explained
      by straightforward SPE method development facilitated by the availability of
      numerous commercial SPE resins. High-speed automated SPE is readily accomplished
      by taking advantage of commercial laboratory robot systems. The present review
      summarizes and discusses advancements made in the use of different SPE resins and
      molecule tagging techniques for optimization of ion-exchange, reversed-phase,
      normal-phase and fluorous-phase SPE in combinatorial chemistry.

PMID- 10941680
TI  - Update on solid-phase extraction for the analysis of lipid classes and related
      compounds.
AB  - This article provides information on the different procedures and methodologies
      developed when solid-phase extraction (SPE) is used for lipid component
      separation. The analytical systematics, established by different authors and
      designed to separate groups of compounds and also specific components by using a
      combination of chromatographic supports and solvents are presented. The review
      has been divided into three parts, which we consider well defined: edible fats
      and oils, fatty foods and biological samples. Separations of non-polar and polar
      lipids is the most extensive systematic, although many other published methods
      have been established to isolate specific components or a reduced number of
      components from edible fats and oils, fatty foods or biological samples
      susceptible to further analysis by other quantitative techniques.

PMID- 10941681
TI  - Ion-pair solid-phase extraction.
AB  - Solid-phase extraction (SPE) is a technique widely employed by analytical
      chemists. SPE cartridges are available in a wide variety of formats containing
      media with diverse chemistries. This paper will review ion-pair SPE, one of the
      less frequently applied, and presumably less well-known techniques. Advantages of
      this technique over more conventional reversed-phase or ion-exchange SPE include
      selectivity, compatibility with rapid evaporative concentration, and potential
      application to multiclass multiresidue analysis.

PMID- 10941682
TI  - Solid- and liquid-phase extraction for the gas chromatographic-tandem mass
      spectrometric quantification of 2,3-dinor-thromboxane B2 and 2,3-dinor-6-oxo
      prostaglandin F1 alpha in human urine.
AB  - Whole body synthesis of thromboxane A2 is best assessed by quantifying non
      invasively its major urinary metabolite, i.e., 2,3-dinor-thromboxane B2 (2,3-dn
      TxB2), by gas chromatography-mass spectrometry (GC-MS) or GC-tandem MS. Methods
      based on these techniques usually require a series of extraction and purification
      procedures including solid-phase extraction (SPE) and thin-layer chromatography
      (TLC) or liquid chromatographic separation of authentic or derivatized 2,3-dn
      TxB2. Taking advantage of the inherent accuracy of GC-tandem MS and the high
      selectivity of the extraction of methoximated 2,3-dn-TxB2 on phenylboronic acid
      SPE cartridges we developed a method that involves only SPE steps prior to
      quantification by GC-tandem MS. The method was validated by performing in
      parallel an additional TLC step. Method mean accuracy and precision were of the
      order of 103% and 95%, respectively. The method allows furthermore co-processing
      of the same urine sample to quantify accurately and rapidly the major urinary
      metabolite of prostacyclin, i.e., 2,3-dn-6-oxo-prostaglandin (PG) F1 alpha, by GC
      tandem MS. The limit of detection of the method was below each 5 pg of 2,3-dn
      TxB2 and 2,3-dn-6-oxo-PGF1 alpha per 5 ml of urine. Our study suggests that dinor
      metabolites of isothromboxanes and isoprostacyclins are not abundantly present in
      human urine.

PMID- 10941683
TI  - Trace determination of antifouling compounds by on-line solid-phase extraction
      gas chromatography-mass spectrometry.
AB  - A new method based on solid-phase extraction (SPE) on-line coupled to gas
      chromatography-mass spectrometry through an on-column interface has been applied
      to determine three antifouling compounds in water samples. Parameters affecting
      the SPE process and transfer step have been optimised and the method developed
      has been applied to the analysis of marinas, fishing ports and Ebro river water.
      The method allows the analytes to be detected at 0.01 microgram l-1 in SIM
      acquisition mode by preconcentrating only 10 ml of water sample. Different marina
      and fishing port water samples have been analysed and Irgarol 1051 has been found
      in some of them at a concentration level equal or lower than 0.05 microgram l-1.

PMID- 10941684
TI  - On-line preconcentration of niobium(V) and tantalum(V) as 4-(2-pyridylazo)
      resorcinol-citrate ternary complexes in geological samples by ion interaction
      high-performance liquid chromatography.
AB  - 4-(2-Pyridylazo) resorcinol (PAR) and citrate were used as pre-column complexing
      agents for the determination of Nb(V) and Ta(V) as ternary complexes in
      geological samples. Aliquots of 2 ml of the standard and sample solutions
      containing the Nb(V) and Ta(V) complexes were loaded onto a concentrator column
      (C18, 0.4 cm x 4.6 mm) with a carrier mobile phase comprising 20% (v/v) methanol
      and containing 5 mM acetic acid, 5 mM citric acid and 10 mM tetrabutylammonium
      bromide (TBABr), pH 6.5 at 2 ml/min for 2 min, with the effluent being directed
      to waste. An automatic switching valve was then switched to flush both complexes
      from the concentrator column onto a C18 analytical column using a mobile phase
      comprising 32% (v/v) methanol and containing 5 mM acetic acid, 5 mM citric acid
      and 3 mM TBABr, pH 6.5 for 2.5 min. The switching valve was then switched back to
      the original position, and cleaned with methanol for 7 min to eliminate unwanted
      species still adsorbed to the concentrator column. This procedure prevented later
      eluting compounds from reaching the analytical column, which reduced the overall
      run time. The detection limits of Nb(V) and Ta(V) (determined at a signal-to
      noise ratio of 3, detection wavelength of 540 nm and a 2-ml sample volume) were
      0.012 and 0.039 ppb for Nb(V) and Ta(V), respectively. Recoveries of Nb(V) and
      Ta(V) were 99.4 and 96.2%, respectively. The HPLC results obtained from the
      reference granite and basalt samples agreed well with inductively coupled plasma
      MS and certified values, but the HPLC method yielded slightly low values of the
      Nb/Ta ratio.

PMID- 10941685
TI  - On-line dual-precolumn-based trace enrichment for the determination of polar and
      acidic microcontaminants in river water by liquid chromatography with diode-array
      UV and tandem mass spectrometric detection.
AB  - Dual-pre-column-based trace enrichment combined on-line with liquid
      chromatography-diode-array UV and tandem mass spectrometric detection was used to
      determine a wide polarity range of organic microcontaminants in river water.
      Various sorbents were studied for their extraction efficiency of (highly) polar
      and acidic compounds and their ability to selectively remove humic substances,
      which are normally co-extracted and interfere in the UV detection of polar
      microcontaminants. An optimised on-line dual-pre-column set-up with PLRP-S in the
      first pre-column and Hysphere-1 in the second pre-column was used to study the
      analytical performance of the procedure. Tandem MS was used for confirmation
      purposes and to quantify the organic microcontaminants in river water at the low
      ng/l level. In addition, the influence of the type of sample (drinking and river
      water) on suppression of analyte responses in electrospray ionization MS was
      studied.

PMID- 10941686
TI  - Solid-phase microextraction in pesticide residue analysis.
AB  - The applications of solid-phase microextraction (SPME) for sample preparation in
      pesticide residue analysis are reviewed in this paper taking into account the
      different approaches of this technique coupled mainly to gas chromatography but
      also to high-performance liquid chromatography. A complete revision of the
      existing literature has been made considering the different applications divided
      according to the pesticide families (organochlorine, organophosphorus, triazines,
      thiocarbamates, substituted uracils, urea derivatives and dinitroanilines among
      others) and the sample matrices analysed which included environmental samples
      (water and soil), food samples and biological fluids. Details on the analytical
      characteristics of the procedures described in the reviewed papers are given, and
      new trends in the applications of SPME in this field are discussed.

PMID- 10941687
TI  - Application of solid-phase microextraction for determination of organic vapours
      in gaseous matrices.
AB  - This paper reviews the practical applications of solid-phase microextraction
      (SPME) in the analysis of organic vapours which are pollutants of atmospheric
      air, indoor air and workplace air. Applications to headspace of solids and
      liquids such as different waters, soils, food, etc., are also included. Problems
      related to calibration in SPME analysis of gaseous matrices are also dealt with.
      Calibration procedures and apparatus for generation of standard gaseous mixtures
      are described. Advantages and limitations of SPME based gas chromatographic
      methods of air organic pollutants are discussed.

PMID- 10941688
TI  - Application of solid-phase microextraction to the recovery of explosives and
      ignitable liquid residues from forensic specimens.
AB  - A current review of the application of solid-phase microextraction (SPME) to the
      analysis of ignitable liquids and explosive residues is presented along with
      experimental results demonstrating the relative effects of controllable
      variables. Variables discussed include fiber chemistry, adsorption and desorption
      temperatures, extraction and desorption times, fiber sampling placement (direct,
      headspace, and partial headspace) and matrix effects, including water content.
      SPME is shown to be an inexpensive, rapid and sensitive method for the analysis
      of ignitable liquids and high explosives residues from solid debris samples and
      from aqueous samples. Explosives are readily detected at parts per trillion
      concentrations and ignitable liquids are reproducibly detected at levels below
      those using conventional methods.

PMID- 10941689
TI  - Role of solid-phase microextraction in the identification of highly volatile
      pheromones of two Rhinoceros beetles Scapanes australis and Strategus aloeus
      (Coleoptera, Scarabaeidae, Dynastinae).
AB  - Solid-phase microextraction (SPME) samplings from live insects or natural
      secretion allowed one to identify the aggregation pheromones of the pest beetles
      Scapanes australis and Strategus aloeus by efficient and rapid isolation of their
      highly volatile (72 < M(r) < 116) components. S. australis male pheromone was
      identified as a 84:12:4 (w/w) mixture of 2-butanol [67:33 (R)-(-):(S)-(+) ratio],
      3-hydroxy-2-butanone and 2,3-butanediol [43:17:40 (R,R)-(-):(S,S)-(+):meso
      ratio], and S. aloeus pheromone as a 95.5:4.0:0.5 (w/w) mixture of 2-butanone, 3
      pentanone and sec.-butyl acetate by GC-MS using conventional and chiral capillary
      columns. This is the first report of Scarabaeidae pheromones based on such small
      and common molecules.

PMID- 10941690
TI  - Solid-phase micro-extraction of drugs from biological matrices.
AB  - Solid phase micro-extraction was originally designed as a technique for the
      solvent-free analysis of volatile organic contaminants in environmental samples.
      However, a wide variety of applications are now being pursued, including the
      analysis of drugs from a variety of matrices. In this review, the analysis of
      drugs by SPME from biological and related matrices, including water, urine,
      blood, hair and saliva, is discussed. A general overview of the special problems
      and techniques involved in SPME from biological matrices is presented, along with
      specific references and discussion of the analysis of many types of drugs and
      metabolites. It is seen that SPME is a highly versatile and flexible technique
      for these analyses.

PMID- 10941691
TI  - Evidence for selectivity of absorption of volatile organic compounds by a
      polydimethylsiloxane solid-phase microextraction fibre.
AB  - Solid-phase microextraction using a 30 microns polydimethylsiloxane fibre has
      been used to sample the volatile organic compounds from standard mixtures and
      from mixtures produced by the decomposition of organic compounds. This method of
      sampling has been compared with the direct injection of an aliquot of headspace
      gas and shows an enrichment factor of approximately 100 over a 1 ml gas injection
      for organosulphur gases such as dimethyldisulphide. The performance of the fibre
      has been evaluated with respect to accuracy and precision at several
      concentrations in representing the composition of multicomponent mixtures. It was
      found that the presence of a second component in a gas sample reduced the
      capacity of the fibre to absorb the primary component. The selectivity of the
      fibre for various volatile compounds with differing functionality was also
      studied. It was found that the non-polar polydimethylsiloxane fibre
      preferentially absorbed the non-polar components of a mixture, e.g. nonane and,
      correspondingly, under reported the more polar components, e.g. ethanol. Hence,
      the fibre discriminates in favour of non-polar and against polar components in a
      mixture in comparison with direct analysis of a headspace sample. Thus,
      quantitation of a component in a multi-component mixture is liable to error from
      competitive interference from other components. A major advantage of the
      technique, however, is that it does not absorb, and therefore introduce, water
      into the analytical system.

PMID- 10941692
TI  - Primary prevention studies and the healthy elderly: evaluating barriers to
      recruitment.
AB  - Although primary prevention studies are important tools in helping the healthy
      elderly stay healthy, recruiting from a community-based cohort of healthy elderly
      individuals for a primary prevention study involves numerous barriers. To better
      identify and understand these barriers, we conducted and evaluated a
      comprehensive recruitment strategy for a primary prevention study testing aspirin
      in an HMO population. In the recruitment phase, we identified healthy individuals
      (65 years of age or older) who were members of a large, group-model HMO in Oregon
      and Washington, and used computerized medical database screening, statistical
      sampling, health plan mailings, e-mail communication with primary care providers,
      and the experience of a well-established research clinic in an effort to enroll
      health elderly in this primary prevention trial. Among a random sample of 47,453
      eligible patients over the age of 65, 44% responded to recruitment efforts, but
      only 3% were enrolled--an overall yield of slightly less than 2%. To evaluate
      these results, we then conducted focus groups with 225 randomly selected
      "eligible refusers." We determined that healthy elders were hesitant to give up
      their choice to use aspirin, unwilling to travel to the research center, and
      reluctant to risk their tenuous hold on good health to participate in a study of
      primary prevention. Awareness of these attitudes is an indispensable step toward
      designing effective recruitment strategies for primary prevention studies
      involving the healthy elderly.

PMID- 10941693
TI  - Abstinence education for urban youth.
AB  - Teen sexual problems in the U.S. are reaching enormous proportions. Attempts to
      prevent common problems, pregnancy and sexually transmitted diseases, are
      underway through the persistent efforts of community, health, academic and
      government organizations. Abstinence education is one of the current attempts.
      However, the lack of well defined theoretical frameworks and analyses of outcomes
      have limited progress in the study of abstinence education. This article
      describes a pilot program in abstinence-only education provided to six groups of
      young teens within an urban middle school. The framework for the program,
      cognitive social learning theory, is described and operationalized. Student
      pretest-posttest attitudes, open-ended written comments about the program and the
      researchers' anecdotes about behavioral changes in the students are the outcome
      measures. Positive attitudes about premarital abstinence increased for all six
      groups; for four of the six groups the increase was statistically significant.

PMID- 10941694
TI  - Attitudes of physicians regarding receiving and storing patients' genetic testing
      results for cancer susceptibility.
AB  - In order to determine interest in and support for a genetic counseling program
      for heritable cancers, a four-item questionnaire was sent to 700 physicians in
      San Diego County likely to encounter patients with significant family histories
      of cancer. Included in the questionnaire was an item requesting information about
      physician attitudes and practices regarding their record keeping for patient
      results of genetic testing for cancer susceptibility. Ninety-two questionnaires
      were returned for a response rate of 13%. The low response rate introduces
      caution when interpreting the results, particularly if the physicians most
      interested in the topic were the most likely to respond. In this light, of note
      was the marked variability found in the attitudes of respondents regarding where
      the results of patients' genetic testing results should be placed in relation to
      the medical record. Whereas one group of physicians would place the testing
      results into the medical record, just as they would any laboratory test result,
      other physicians do not even want written notice of the results in order to
      maintain patient confidentiality. Another group acknowledges the sensitivity of
      the information, but prefers to store genetic testing results separately, as they
      would results of HIV testing or history of psychiatric treatment. Genetic testing
      for cancer susceptibility is associated with patient concerns regarding
      confidentiality of testing results and fears of the consequences of release of
      this information to insurance companies. While the small and possibly biased
      sample must be considered when interpreting the results, the lack of consistency
      among physicians about where to store genetic testing results in terms of the
      patient medical record underscores the need for both a consensus statement and
      legal protection for both patient and physician. Variability in physician
      practices suggests that the process of obtaining informed consent for genetic
      testing should include a discussion with the patient about how the
      confidentiality of test results will be maintained.

PMID- 10941695
TI  - Older, hypertensive, and hypercholesterolemic fairgoers visit more booths and
      differ in their health concerns at a community health fair.
AB  - The purpose of this study was to determine whether persons attending a community
      health fair had different health concerns and booth visitation patterns based on
      their risk factor profiles. All fairgoers were encouraged to complete an
      anonymous survey of demographic information, top 4 health concerns, and selected
      cardiac risk factors. Over the five-hour duration of the fair, 329 surveys were
      collected from about 450 fairgoers. There were no exclusion criteria for the
      survey. The fair was sponsored by the Maryland Chapter of the American College of
      Physicians, organized by medical students from the University of Maryland and
      Johns Hopkins University, and included 23 booths on a variety of health topics.
      Older fairgoers and fairgoers with a self-reported history of high blood pressure
      or elevated cholesterol showed an increased interest in hypertension and heart
      disease (p < 0.05). Older fairgoers also showed an increased interest in health
      topics related to aging, such as estrogen replacement therapy and geriatric
      medicine. Older, hypertensive and hypercholesterolemic fairgoers visited an
      increased mean number of total booths when compared to other respondents (p <
      0.05). Most booths reported a higher percentage of older, hypertensive, and
      hypercholesterolemic visitors than the overall percentage of fairgoers who
      reported these risk factors. These results suggest that booth visitation patterns
      of health fair participants may be viewed as a deliberate attempt by at risk
      populations to access health information particular to their needs.

PMID- 10941696
TI  - A national survey of sun safety activities at U.S. zoos.
AB  - Skin cancer incidence in the United States has increased. Exposure to ultraviolet
      radiation (UVR) is a major risk factor for skin cancer. Every year, millions of
      children with their families visit outdoor leisure facilities such as zoos where
      overexposure to UVR may occur. This study was conducted to assess the proportion
      of U.S. zoos that provided sun safety activities during the summer of 1998 and
      their willingness to incorporate skin cancer prevention strategies at their
      facility in the future. A 56 item self-administered questionnaire was mailed to
      140 zoos accredited by the American Zoo and Aquarium Association. A follow-up
      telephone survey was also conducted with 33 mail non-respondents. The response
      rate was 97% (N = 136). Results revealed that in the summer of 1998, only 5% of
      zoos provided sun safety recommendations to visitors and 25% of zoos provided
      recommendations to their employees. The recommendations made most often to
      visitors and employees were to use sunscreen and wear protective clothing. Eighty
      five percent of zoos indicated interest in providing sun safety activities at
      their facilities in the future. The next step will be to design environmentally
      appropriate sun safety programs for zoos and to encourage zoos to implement these
      programs.

PMID- 10941697
TI  - Kentucky pharmacists' opinions and practices related to the sale of cigarettes
      and alcohol in pharmacies.
AB  - The objective of the study was to augment important findings from a 1996
      statewide survey of Indiana pharmacists regarding their opinions and practices
      related to the sale of cigarettes and alcohol in pharmacies. More specifically,
      this study was designed (1) to determine opinions and practices of Kentucky
      pharmacists' related to the sale of cigarettes and alcohol; (2) compare these
      findings with results from the Indiana study; and (3) to gather information on
      health promotion activities by Kentucky pharmacists. A structured survey
      questionnaire was designed and reviewed by a jury of experts and subsequently
      administered to half of the 1182 pharmacies in Kentucky. Collected data were
      analyzed by using descriptive and inferential statistical methods. Findings
      reveal that 45 percent of responding pharmacists sell cigarettes in their stores
      even though 88 percent think that their stores should not sell cigarettes.
      Approximately 34 percent of the pharmacies in non-dry counties sell alcoholic
      beverages while more than four-fifths of the pharmacists (81%) think pharmacies
      should not sell alcoholic beverages. After adjusting by type of pharmacy, no
      statistical difference was found in retail-chain pharmacy sales of cigarettes and
      alcohol in either Kentucky or Indiana. However, independent pharmacies in
      Kentucky were less likely to sell cigarettes and alcohol compared to independent
      Indiana pharmacies. Study results also revealed that most pharmacists agree the
      use of cigarettes and alcohol are important causes of morbidity and pre-mature
      mortality and that pharmacists should play a role in health promotion and disease
      prevention through their relationship with the public. However, the majority do
      not ask their patients about their smoking and alcohol habits and do not
      participate in health education/promotion programs for the general community.

PMID- 10941698
TI  - The Mayman contributions.

PMID- 10941699
TI  - On the object relational texture of affects.
AB  - Marty Mayman will be remembered as a uniquely gifted clinician, diagnostician,
      supervisor, and teacher. In this article, I link his distinctive capacity for
      empathic understanding to his reliance on self-representational and object
      representational concepts as a vehicle for accessing the inner life of his
      participant. Mayman's special brand of empathy was remarkable for its sensitivity
      to nuance as well as its ability to strike a chord with vivid resonance. His
      understanding of ego development included the notion that self-representation and
      object representation make up part of the internalized structure of all ego
      functions. Self- and object representations can be thought of as embedded in the
      individual's subjective experience of the very performing of those ego functions.
      Self- and object representations can also be thought of as embedded in the
      individual's attitudes toward the exercising of particular ego functions, for
      example, where the individual struggles with whether or not he or she feels a
      sense of permission to "own" or exercise specific ego capacities. In this
      article, I apply the use of self- and object representation as a way of
      "texturizing" the ego to the way object relations are embedded within affects. I
      use some Early Memory Test (Mayman, 1968) material to elucidate the role of
      object relational themes in the specific way in which affects are experienced.

PMID- 10941700
TI  - Martin Mayman's early memories technique: bridging the gap between personality
      assessment and psychotherapy.
AB  - In this article, we describe Martin Mayman's approach to early childhood memories
      as a projective technique, beginning with his scientific interest in learning
      theory, coupled with his interest in ego psychology and object relations theory.
      We describe Mayman's contributions to the use of the early memories technique to
      inform the psychotherapy process, tying assessment closely to psychotherapy and
      making assessment more useful in treatment. In this article, we describe a
      representative sample of research studies that demonstrate the reliability and
      validity of early memories, followed by case examples in which the early memories
      informed the therapy process, including issues of transference and
      countertransference.

PMID- 10941701
TI  - Martin Mayman: his work and his place.

PMID- 10941702
TI  - On the science of Rorschach research.
AB  - Wood et al.'s (1999b) article contained several general points that are quite
      sound. Conducting research with an extreme groups design does produce effect
      sizes that are larger than those observed in an unselected population.
      Appropriate control groups are important for any study that wishes to shed light
      on the characteristics of a targeted experimental group and experimental validity
      is enhanced when researchers collect data from both groups simultaneously.
      Diagnostic efficiency statistics--or any summary measures of test validity-
      should be trusted more when they are drawn from multiple studies conducted by
      different investigators across numerous settings rather than from a single
      investigator's work. There should be no question that these points are correct.
      However, I have pointed out numerous problems with specific aspects of Wood et
      al.'s (1999b) article. Wood et al. gave improper citations that claimed
      researchers found or said things that they did not. Wood et al. indicated my data
      set did not support the incremental validity of the Rorschach over the MMPI-2
      when, in fact, my study never reported such an analysis and my data actually
      reveal that the opposite conclusion is warranted. Wood et al. asserted there was
      only one proper way to conduct incremental validity analyses even though experts
      have described how their recommended procedure can lead to significant
      complications. Wood et al. cited a section of Cohen and Cohen (1983) to bolster
      their claim that hierarchical and step-wise regression procedures were
      incompatible and to criticize Burns and Viglione's (1996) regression analysis.
      However, that section of Cohen and Cohen's text actually contradicted Wood et
      al.'s argument. Wood et al. tried to convince readers that Burns and Viglione
      used improper alpha levels and drew improper conclusions from their regression
      data although Burns and Viglione had followed the research evidence on this topic
      and the expert recommendations provided in Hosmer and Lemeshow's (1989) classic
      text. Wood et al. oversimplified issues associated with extreme group research
      designs and erroneously suggested that diagnostic studies were immune from
      interpretive confounds that can be associated with this type of design. Wood et
      al. ignored or dismissed the valid reasons why Burns and Viglione used an extreme
      groups design, and they never mentioned how Burns and Viglione used a homogeneous
      sample that actually was likely to find smaller than normal effect sizes. Wood et
      al. also overlooked the fact that Burns and Viglione identified their results as
      applying to female nonpatients; they never suggested their findings would
      characterize those obtained from a clinical sample. Wood et al. criticized
      composite measures although some of the most important and classic findings in
      the history of research on personality recommend composite measures as a way to
      minimize error and maximize validity. Wood et al. also were mistaken about the
      elements that constitute an optimal composite measure. Wood et al. apparently
      ignored the factor-analytic evidence that demonstrated how Burns and Viglione
      created a reasonable composite scale, and Wood et al. similarly ignored the clear
      evidence that supported the content and criterion related validity of the EMRF.
      With respect to the HEV, Wood et al. created a z-score formula that used the
      wrong means and standard deviations. They continued to use this formula despite
      being informed that it was incorrect. Subsequently, Wood et al. told readers that
      their faulty z-score formula was "incompatible" with the proper weighted formula
      and asserted that the two formulas "do not yield identical results" and "do not
      yield HEV scores that are identical or even very close." These published claims
      were made even though Wood et al. had seen the results from eight large samples,
      all of which demonstrated that their wrong formula had correlations greater than
      .998 with the correct formula. At worst, it seems that Wood et al. (199

PMID- 10941703
TI  - Interaction of therapeutic process and alliance during psychological assessment.
AB  - Utilizing a collaborative therapeutic assessment (TA) model proposed by Finn and
      Tonsager (1997), we examined the interaction between therapeutic alliance and in
      session process during the assessment phase of treatment. This study compares the
      utility of the TA model (n = 38) versus a traditional information gathering model
      (n = 90) of assessment. The results of this study indicate that the use of a TA
      model may decrease the number of patients who terminate treatment against medical
      advice. The Session Evaluation Questionnaire (Stiles & Snow, 1984), Combined
      Alliance Short Form (Hatcher & Barends, 1996), and Penn Helping Alliance
      Questionnaire-Revised (Barber & Crits-Christoph, 1996) can reliably measure the
      patient's experience of the assessment. The psychological assessment process may
      impact the patient's experience of assessment feedback and aid in the development
      of a therapeutic alliance. The therapeutic alliance developed during the
      assessment was found to be related to alliance early in psychotherapy. We discuss
      the theoretical, clinical, and research implications of these findings.

PMID- 10941704
TI  - The Millon adolescent clinical inventory and psychopathy.
AB  - We investigated the ability of the Millon Adolescent Clinical Inventory (MACI;
      Millon, 1993) to assess psychopathy as measured by the Psychopathy Checklist-
      Revised (PCL-R; Hare, 1991). Participants were 90 adolescents in an inpatient
      psychiatric unit. The MACI Substance Abuse Proneness (r = .47), Unruly (r = .43),
      and Submissive (r = -.42) scales correlated most strongly with the PCL-R. Using a
      discriminant function analysis, the Substance Abuse Proneness scale correctly
      distinguished between high- and low-psychopathy groups in 79% of cases. Using a
      rational approach, we developed a psychopathy content scale using 20 MACI items.
      This content scale correlated with the PCL-R (r = .60) and distinguished high-
      and low-psychopathy groups in 83% (kappa = .66) of cases (sensitivity = 85%,
      specificity = 81%).

PMID- 10941705
TI  - Selected Rorschach variables of psychopathic juvenile offenders.
AB  - Despite the widely accepted utility of assessing psychopathic personality
      features in forensic and clinical settings, the Hare Psychopathy Checklist
      Revised (PCL-R; Hare, 1991) stands virtually alone in its ability to do so with
      adequate reliability and validity. Recent studies have demonstrated the
      effectiveness of the Rorschach Inkblot Method in assessing psychopathy in adult
      samples, but almost no studies are currently available investigating the
      Rorschach's ability to assess the condition in younger samples of precisely
      defined psychopathic groups. In this study, 66 male juvenile offenders, ages 14
      to 17, were placed into 3 groups according to level of psychopathy as measured by
      the youth version of the PCL-R (PCL:YV; Forth, 1995). Nine Rorschach variables
      conceptually related to various psychopathic features were investigated. Two of
      the variables (Reflections and Texture Responses) demonstrated statistically
      significant differences across groups (p < .05). Two additional variables (Vista
      and White Space) were produced in patterns consistent with existing research,
      although only to a weak degree. The remaining variables (Egocentricity Index,
      Form Dimension, Pure Human Content, Inanimate Movement, and Diffuse Shading) did
      not differ across groups in the predicted directions. Overall, these results
      offer some support for the validity of the Rorschach as a method of detecting
      certain psychopathic personality features, including pathological narcissism and
      interpersonal detachment, in adolescent male offenders.

PMID- 10941706
TI  - Rorschach protocols from children and adolescents diagnosed with posttraumatic
      stress disorder.
AB  - Rorschach protocols from 35 children and adolescents with posttraumatic stress
      disorder (PTSD) and 35 with oppositional defiant disorder (ODD) were compared.
      Both groups revealed significant differences from the normative tables on the
      same 12 variables: SCZI, DEPI, CDI, X + %, EgoC, Afr, T, EA, P, WSumC, RawSumSS,
      and WgtSumSS. However, as predicted, 4 of those variables, the Schizophrenic
      Index (SCZI) and 3 of the criterion tests that comprise it (X + %, RawSumSS, and
      WgtSumSS) were significantly different between the PTSD and ODD groups, with the
      PTSD group responding with more extreme scores. These findings contradict Exner's
      (1993) statement that only people with schizophrenia can be "defined or
      conceptualized as having both the problems of disordered thinking and inaccurate
      perception" (p. 356). Children and adolescents with PTSD also display these
      problems when trauma interrupts the child's naive belief that the world has
      predictable rules, the people in it are trustworthy and fair, and punishment and
      pain are consequences of bad behavior. When young victims cannot comprehend or
      make sense of what has happened to them, life becomes irrational, illogical, and
      confusing. Exner's SCZI does what it was designed to do: identify individuals
      with disordered thinking and inaccurate perception. Therefore, SCZI should be
      renamed the Perception and Thinking Index (PATI) to reflect its function rather
      than a diagnostic category.

PMID- 10941707
TI  - Assessment of hostility in patients with coronary heart disease.
AB  - One of the problems in efforts to more clearly conceptualize hostility is the
      amount of method variance, which ranges from self-report techniques to interview
      based methods and mirrors the multidimensional nature of hostility and related
      constructs. In addition, rather few studies concerned with the assessment of
      hostility have specifically used samples of coronary heart disease (CHD)
      patients. The purpose of this study was, therefore, to examine the
      multidimensionality of the construct of hostility in a sample of male coronary
      patients with some frequently used instruments. Factor analysis was used to
      detect the relevant underlying constructs, which were assessed using a variety of
      hostility measures in a sample of cardiac patients undergoing baseline assessment
      in an ongoing health-education intervention study. Measurement included both
      questionnaires and interviews. Participants (N = 235) were divided into 3
      diagnostic groups: patients who had recently undergone (a) a myocardial
      infarction, (b) coronary artery bypass grafting, or (c) percutaneous transluminal
      coronary angioplasty. A 4-factor solution appeared to provide the best fit, and
      the following factors were isolated: Anger-Out, Negative Affect, Coping, and
      Anger-In. All intercorrelations were less than .50. Medical diagnosis did not
      differ with regard to the 4 factors found. The total hostility construct as
      measured by the structured interview (SI) did not fit into the 4-factor model.
      This study was the first to show that dimensions of anger and hostility
      constitute valid and relevant aspects of the general construct of hostility for a
      representative group of CHD patients. The 4 aspects of hostility isolated using
      some well-known hostility questionnaires and the SI explained most of the
      observed variance. Although the SI appeared to tap more general state anger, the
      4 aspects of hostility may be differentially related to health in those who are
      coronary prone. Future studies on the role of hostile or negative emotions in CHD
      patients should, therefore, pay greater attention to the multidimensional nature
      of hostility and may clearly benefit from the use of the 4-factor model described
      in this article.

PMID- 10941708
TI  - Aging and middle ear resonance.
AB  - Tympanograms for probes ranging from 250 through 2000 Hz were evaluated for 467
      older adults. Measures of middle ear resonant frequency were compared across age
      groups (48-59, 60-69, 70-79, 80-90 years) and gender. No significant age group
      trends were observed for middle ear resonant frequency. Middle ear resonant
      frequencies were significantly higher for older women than for older men, but the
      differences were small.

PMID- 10941709
TI  - Comparison of performance across three directional hearing aids.
AB  - This study compared the speech recognition performance of 12 hearing-impaired
      listeners fit with three commercially available behind-the-ear hearing aids in
      both directional and omnidirectional modes. One digitally programmable analog and
      two "true digital" hearing aids were selected as test instruments. Testing was
      completed in both "living room" and anechoic room environments. Speech
      recognition was examined using modified forms of the Hearing in Noise Test and
      the Nonsense Syllable Test. The single competing stimuli of these tests were
      replaced with five uncorrelated competing sources. Results revealed a significant
      speech recognition in noise advantage for all directional hearing aids in
      comparison to their omnidirectional counterparts. Maximum performance of the
      directional hearing aids did not significantly vary across circuit type,
      suggesting that processing differences did not affect maximum directional hearing
      aid performance. In addition, the results suggest that performance in one
      reverberant environment cannot be used to accurately predict performance in an
      environment with differing reverberation.

PMID- 10941710
TI  - Hearing-aid-processed tone pips: electroacoustic and ABR characteristics.
AB  - The auditory brainstem response (ABR) recorded while wearing a hearing aid may
      supply supplemental information about the benefit and appropriateness of the
      hearing aid for certain infants. The purposes of this study were (1) to determine
      the effects of different output limiting circuits on the acoustics of tone-pip
      stimuli used for ABR recordings and (2) assess how changes in hearing-aid
      processed stimuli affect ABR characteristics. Electroacoustic input/output
      functions to tone-pip stimuli were constructed for three different output
      limiting circuits (wide dynamic range compression, output compression, and linear
      with peak clipping) available in a programmable hearing aid. Wave V latency and
      amplitude functions were then measured to the same stimuli and hearing aid
      settings in five normal-hearing adults. Electroacoustic results showed that none
      of the output limiting circuits, including linear peak clipping, were effectively
      activated by tone pips compared to the hearing aid performance to continuous
      tones. Aided wave V latency and amplitude functions were asymptotic to high
      stimulus levels, suggesting that cochlear output was in saturation.

PMID- 10941711
TI  - Auditory temporal and spectral resolution in normal and impaired hearing.
AB  - Temporal, spectral, and combined temporal-spectral resolution of hearing was
      assessed by recording masked hearing thresholds. The masker was an octave band
      noise. Spectral resolution was assessed by introducing a spectral gap of half an
      octave bandwidth in the masker. A 50-msec gap assessed temporal resolution. The
      spectral and temporal gaps were used separately or simultaneously. Normal-hearing
      and hearing-impaired subjects participated. For each masking condition, the
      subjects were tested at masker levels 50, 60, 70, and 80 dB SPL and at test-tone
      frequencies 0.5, 1, 2, and 4 kHz. Normal-hearing subjects showed reduced masking
      with spectral and temporal gaps. The combination of spectral and temporal gap
      reduced masking further. The release of masking was dependent upon the masker
      level. Hearing-impaired subjects showed less release of masking than normal
      hearing subjects. The degree of hearing impairment was inversely related to
      release of masking. Reliability of the test procedure was assessed.

PMID- 10941712
TI  - Test-retest stability and short-term habituation of the N1 and gamma band
      response.
AB  - The gamma band response (GBR) is an exogenous, cortically generated, event
      related potential that occurs between 20- and 170-msec post-stimulus onset. The
      auditory GBR is superimposed on the transient evoked middle and long latency
      cortical auditory evoked potentials and demonstrates a peak spectral frequency
      between 30 and 40 Hz. The present investigations were conducted to evaluate the
      test-retest stability and short-term habituation of the GBR. Both the GBR and N1
      were recorded from six normal-hearing, neurologically intact subjects
      (Investigation 1, test-retest stability) and two subjects with intractable
      epilepsy with implanted subdural electrode grid arrays (Investigation 2, short
      term habituation characteristics). For Investigation 1, the test-retest interval
      was 1 month. For Investigation 2, 300 samples were acquired per stimulus block (a
      10-minute interval) and then subaveraged in blocks of 25 to 50 samples each.
      Results suggest that (1) like N1, the GBR shows high repeatability (qualitative)
      and test-retest stability (quantitative) and (2) the GBR does not demonstrate
      evidence of short-term habituation.

PMID- 10941713
TI  - Stimulus length uncertainty with dichotic digit recognition.
AB  - Dichotic digit listening was made more difficult by interleaving one-, two-,
      three-, and four-pair digits within a test list in which the subjects did not
      know a priori the number of digit pairs presented on a given trial, thereby
      introducing listener uncertainty. Twenty right-handed (mean age = 26.8 years) and
      20 left-handed adults (mean age = 24.0) with normal hearing and 40 right-handed
      adults in the 60- to 75-years age range (mean age = 67.2) with mild-to-moderate
      sensorineural hearing loss were evaluated. Compared to traditional paradigms, the
      uncertainty of stimulus length (one, two, three, or four pairs) reduced overall
      recognition performance on stimuli presented to both ears of all groups, but the
      reduction was more pronounced for the left ear than for the right ear. The
      recognition performance of the right-handed subjects was more homogeneous than
      the performance of the left-handed subjects. In comparison to the young subjects,
      the 60- to 75-year-old group had substantially reduced recognition performance.

PMID- 10941714
TI  - Longitudinal study of serum copper and zinc levels and their distribution in
      blood proteins after acute myocardial infarction.
AB  - The levels and distribution of serum Cu and Zn were studied in patients diagnosed
      with acute myocardial infarction from the day of admission to the Cardiovascular
      Intensive Care Unit until the 10th day following the attack. The results obtained
      show that Cu increases significantly (p < 0.01) after the 5th day after the acute
      myocardial infarction, while Zn decreases significantly (p < 0.01) with respect
      to the control group from the first day on, with the lowest values being found on
      the 3rd day after the attack. Further, total serum Cu showed an excellent
      correlation with the albumin-bound and globulin-bound Cu (ceruloplasmin), as well
      as with the concentrations of both serum protein fractions. In contrast, total
      serum Zn only presents this correlation with Zn bound to albumin, but not with Zn
      bound to globulin nor with the albumin concentration. These findings suggest the
      existence of some type of relationship between the two fractions of the element
      bound to protein. This relationship is probably different for both metals.

PMID- 10941715
TI  - Gold and palladium burden from dental restoration materials.
AB  - From 81 volunteers (16 without dental restorations, 65 with gold crowns or
      inlays) samples of saliva before and after chewing gum, blood, serum, urine and
      faeces were taken and analysed for gold (Au) and palladium (Pd). The Au
      concentration in all analysed biomonitors correlates significantly to the number
      of teeth with gold restorations. For Pd the correlations were still significant,
      but weaker than for Au. Persons with gold restorations show maximal Au and Pd
      concentrations, 10(2)-10(3) higher than the background burden. The calculated
      maximal daily Au load in saliva (1.38 mg Au per day) reaches the range of an oral
      Au therapy for rheumatoid arthritis with 6 mg Auranofin (= 1.74 mg Au per day).
      During this therapy severe and frequent side effects are reported. In contrast,
      the Au concentration in serum maximally reached from Au restorations, amounts to
      only approximately 1/20 of the Au level during arthritis therapy. But even under
      subtherapeutic doses of 1 mg Auranofin/day severe side effects have been reported
      (4 out of 56 cases). The mean Au blood concentration from 1 mg Auranofin daily
      was only 3 times higher than our maximum value. A toxicological classification of
      the Pd values is difficult, because no toxicological threshold limit has been
      established, especially for the low-level long-term burden with Pd.

PMID- 10941716
TI  - Dietary cadmium decreases lipid peroxidation in the liver and kidneys of the bank
      vole (Clethrionomys glareolus).
AB  - The effect of elevated levels of dietary cadmium on lipid peroxidation in the
      liver and kidneys of a small rodent, the bank vole, was determined in the present
      study. Males and females, aged 1 month, were given diets containing 0.40 and 80
      mg Cd per kg; liver and kidneys were removed for TBA-RS as well as iron, copper,
      zinc, cadmium and metallothionein analyses at the end of 6 weeks. Dietary Cd
      significantly decreased the TBA-RS level in the liver and kidneys of both sexes;
      however, this effect appeared to be dose-dependent only for the male liver. The
      changes in hepatic and renal TBA-RS paralleled closely those of tissue iron.
      Copper concentration decreased significantly only in the male liver, while
      hepatic and renal zinc were not influenced by dietary Cd. The concentrations of
      Cd and metallothionein in the liver and kidneys increased significantly in a dose
      dependent fashion. Regression analysis confirmed that TBA-RS in both organs
      correlated closely with iron. The data suggest that dietary Cd decreases hepatic
      and renal lipid peroxidation indirectly, through lowering the tissue iron
      concentration.

PMID- 10941717
TI  - Lithium effect on testicular tissue and spermatozoa of viscacha (Lagostomus
      maximus maximus). A comparative study with rats.
AB  - We investigated the effect of lithium chloride administration (Sigma): 1 mmol/kg
      b.w. i.p./day for 35 days on the testes and sperm of viscacha (Lagostomus maximus
      maximus), a nocturnal rodent found only in the pampas of Argentina. The
      histological study showed that hypospermatogenesis and the sperm number per mL
      decreased markedly in comparison with the controls (treatment group: 315 x 10(6)
      +/- 77 x 10(6); control group: 693 x 10(6) +/- 39 x 10(6), Means +/- SEM,
      Student's t-test: p < 0.05). The sperm motility and viability were also affected.
      Under the same treatment, the testicular tissue and the sperm of rats were not
      damaged. Moreover, lithium induced these changes when the plasm levels were
      within the therapeutic range in humans. Our results provide evidence for the
      claim that viscacha testes and sperm react very sensitively to low doses of
      lithium, whereas these concentrations do not produce damage in rats.

PMID- 10941718
TI  - Effect of supplementation with organic selenium on mercury status as measured by
      mercury in pubic hair.
AB  - The purpose of this study was to evaluate the effect of four months of yeast
      based selenium supplementation on selenium and mercury status in subjects with
      low serum selenium. The study was carried out in Rakvere, Estonia. Pubic hair
      mercury, serum selenium and blood selenium concentrations in 23 subjects (serum
      selenium < 90 micrograms/l) were investigated before and after selenium
      supplementation. Thirteen subjects were randomized into the selenium
      supplementation group and ten into the placebo group. The selenium
      supplementation group received daily 100 micrograms of selenomethionine. Selenium
      supplementation reduced pubic hair mercury level by 34% (p = 0.005) and elevated
      serum selenium by 73% and blood selenium by 59% in the supplemented group (p <
      0.001 for both). The study indicates that mercury accumulation in pubic hair can
      be reduced by dietary supplementation with small daily amounts of organic
      selenium in a short range of time.

PMID- 10941719
TI  - Concentrations of copper, zinc and various elements in serum of patients with
      bronchial asthma.
AB  - In this study, serum copper, zinc, magnesium, iron and calcium concentrations
      were investigated in 40 patients with bronchial asthma (BA) and in 43 healthy
      subjects. Copper and calcium levels were found to be increased in patients with
      BA compared to the control group (p < 0.001 and p < 0.001 respectively). On the
      other hand, the serum zinc level was significantly lower in healthy subjects (p <
      0.01). No changes were found in serum magnesium and iron levels in patients with
      BA compared to controls. In addition to various elements, certain serum proteins
      such as albumin, transferrin and ferritin were also assessed to determine whether
      there was a relationship between the elements and proteins in patients with BA.
      There was only a significant decrease in albumin concentration in patients with
      BA (p < 0.05).

PMID- 10941720
TI  - Determination of iron, copper, zinc, magnesium and selenium in plasma and
      erythrocytes in neurosurgical patients.
AB  - A direct method for determination of Fe, Cu, Zn, Mg and Se in erythrocytes was
      developed. The aim of the present study was to establish a method for examining
      perioperative levels of the above mentioned elements simultaneously in
      erythrocytes and plasma by atomic absorption spectrophotometry in 11 patients
      undergoing neurosurgery for acute spinal nerve compressions because of
      intervertebral disk prolapses. Reference values for erythrocytes were 11.49 +/-
      3.48 mmol/mmol Hb; 0.82 +/- 0.087 mmol/mmol Hb; 9.01 +/- 2.20 mmol/mmol Hb; 0.104
      +/- 0.032 mmol/mmol Hb; 0.07 +/- 0.050 mmol/mmol Hb for iron, copper, zinc,
      magnesium, and selenium, respectively. Postoperative erythrocyte concentrations
      did not differ significantly compared to those obtained preoperatively and
      remained within the reference ranges perioperatively. For plasma the following
      reference values were used: 19.0 +/- 8.0 mmol/l (Fe); 20.1 +/- 8.2 mmol/l (Cu);
      15.4 +/- 4.6 mmol/l (Zn); 0.9 +/- 0.15 mmol/l (Mg); 1.02 +/- 0.3 mmol/l (Se).
      There was a significant decrease in the concentration of copper in plasma (13.41
      +/- 3.46 mmol/l, p < 0.1) and zinc (10.73 +/- 2.73 mmol/l, p < 0.1) immediately
      postoperative, iron (10.56 +/- 3.91 mmol/l, p < 0.1) and zinc on day 1 (11.28 +/-
      1.88 mmol/l, p < 0.10), and a significant postoperative increase of copper on day
      5 (18.81 +/- 3.97 mmol/l, p < 0.1), postoperatively. The mean plasma
      concentrations of iron, copper, zinc magnesium and selenium remained within the
      reference ranges during the entire period.

PMID- 10941721
TI  - Application of focused-microwave wet digestion to the determination of trace
      metals in human gallstones by ICP/AES.
AB  - We propose an analytical digestion method for trace metal determination (Co, Cr,
      Cu, Fe, Mn, Ni and Zn) in gallstones, in an attempt to facilitate detection of
      their origin. The method consists of sample digestion with HNO3 and H2O2 by means
      of focused microwave. Metals are quantified by inductively coupled plasma atomic
      emission spectroscopy. The effect of calcium concentration in the analytical
      solutions was studied. Cu, Fe, Mn and Zn were detected in all the samples
      analysed and the highest concentrations were obtained for Cu and Fe, especially
      in black-pigmented gallstones. The reproducibility in terms of %RSD, determined
      in the gallstones with the lowest metal content, was below 5% for Cu, between 10%
      and 15% for Mn and Zn and up to 25% for Fe.

PMID- 10941722
TI  - Elements in autopsy liver tissue samples from Greenlandic Inuit and Danes. II.
      Iron measured by X-ray fluorescence spectrometry.
AB  - The purpose of this study was to measure the content of iron (Fe) in liver tissue
      samples from urbanized Greenlandic Inuit using X-ray fluorescence spectrometry,
      and compare the results with those obtained in liver tissue samples from
      urbanized Danes. Normal liver tissue samples were obtained at autopsy from 50
      Greenlandic Inuit (27 men, 23 women) with a median age of 61 years (range 23-83)
      and from 72 Danes (42 men, 30 women) with a median age of 62 years (range 15-87).
      In the entire series, there was no significant difference between liver iron in
      Inuit compared with Danes. Likewise, there was no significant gender difference
      concerning liver iron content, either in Inuit or in Danes. The median iron
      content (with 5-95 percentile) in Inuit was 17.23 mmol/kg dry liver (5.80-91.80)
      and in Danes 16.51 mmol/kg dry liver (7.83-39.05). However, when stratified
      according to age, a trend was revealed showing that Inuit men and women < or = 50
      years had a lower liver iron content than Danes (p = 0.05 and p = 0.08) whereas
      Inuit men and women > 50 years had a higher liver iron content than Danes (p =
      0.18 and p = 0.02). There was a significant correlation between liver iron
      content and age in both Inuit men (rs = 0.49, p = 0.01) and in women (rs = 0.64,
      p = 0.003), but not in Danes. In Inuit, the median hepatic iron index (liver iron
      content divided by age) was 0.33 in men and 0.32 in women. The median estimated
      iron content in the whole liver was 6.54 mmol (365 mg) in Inuit men and 5.41 mmol
      (302 mg) in Inuit women (p = 0.6). There was no correlation between hepatic iron
      index and age. In Danes, the median hepatic iron index was 0.46 in men and 0.29
      in women (p = 0.01). There was a significant inverse correlation between hepatic
      iron index and age in the two genders and in the entire series (rs = -0.71, p =
      0.0001). The results indicate that young and middle-aged urbanized Inuit have
      slightly smaller iron stores than urbanized Danes, whereas elderly Inuit have
      higher iron stores than Danes. In Danes, iron stores plateau at 30 to 40 years of
      age in men and some years after the menopause in women. In Inuit, iron stores
      continue to increase in old age, probably to due a lifelong dietary intake of
      haem iron.

PMID- 10941723
TI  - A preliminary clinical investigation into the potential of blood lead levels to
      measure bone resorption in patients with skeletal metastases, using ICP-MS.
AB  - A simple, accurate and precise method to measure lead levels in whole blood by
      inductively coupled plasma-mass spectrometry (ICP-MS) has been developed. Blood
      samples were diluted (1 + 9) with 0.1% v/v Triton X-100 and 0.1% v/v nitric acid,
      and gave a limit of detection of 0.06 microgram/l (3sn). Spiking experiments
      demonstrated recoveries of 100 +/- 10% and verification against Seronorm
      reference and BCR certified reference materials gave experimental values in close
      agreement to the reference values. The methodology was used to conduct a
      feasibility study, involving a preliminary clinical investigation to assess the
      potential of whole blood lead levels as biochemical markers to measure bone
      resorption in patients with skeletal metastases and receiving treatment. The
      results from this feasibility study showed that the method remained under
      analytical control, giving inter and intra assay coefficients of variation of <
      5%. This feasibility study also showed that the changes in the blood lead levels
      within individual patients were measurable and in many cases the patient's
      observed clinical performance demonstrated similar trends to the blood lead
      levels measured over time. Overall the results were encouraging and showed
      promise. Further and more detailed investigations into the use of lead and other
      trace metals as biomarkers of bone resorption is warranted.

PMID- 10941724
TI  - Review of publications.

PMID- 10941725
TI  - Methylmercury accumulation in tissues and its effects on growth and appetite in
      captive great egrets.
AB  - To test the hypothesis that fledging wading birds would be more at risk from
      mercury toxicosis than younger nestlings, captive great egret nestlings were
      maintained as controls or were dosed from 1- to 14-wk-old with 0.5 or 5 mg
      methylmercury chloride/kg wet weight in fish. Birds dosed with 5 mg/kg suffered
      from subacute toxicosis at wk 10-12. Growing feather concentrations were the most
      closely correlated with cumulative mercury consumed per weight. Blood
      concentrations of mercury increased more rapidly after 9 wk in all groups when
      feathers stopped growing. Total mercury accumulated in tissues in concentrations
      in the following order: growing scapular feathers > powderdown > mature scapular
      feathers > liver > kidney > blood > muscle > pancreas > brain > bile > fat > eye.
      The proportion of total mercury that was methylated depended upon tissue type and
      dose group. Selenium accumulated in liver in direct proportion to liver mercury
      concentrations. After wk 9, appetite and weight index (weight/bill length)
      declined significantly in both dosed groups. At current exposure levels in the
      Everglades (Florida, USA) mercury deposited in rapidly growing feathers may
      protect nestlings from adverse effects on growth until feathers cease growing.

PMID- 10941726
TI  - Histologic, neurologic, and immunologic effects of methylmercury in captive great
      egrets.
AB  - Captive great egret (Ardea albus) nestlings were maintained as controls or were
      dosed with methylmercury chloride at low (0.5), and high doses (5 mg/kg, wet
      weight) in fish. Low dosed birds were given methylmercury at concentrations
      comparable to current exposure of wild birds in the Everglades (Florida, USA).
      When compared with controls, low dosed birds had lower packed cell volumes, dingy
      feathers, increased lymphocytic cuffing in a skin test, increased bone marrow
      cellularity, decreased bursal wall thickness, decreased thymic lobule size, fewer
      lymphoid aggregates in lung, increased perivascular edema in lung, and decreased
      phagocytized carbon in lung. High dosed birds became severely ataxic and had
      severe hematologic, neurologic, and histologic changes. The most severe lesions
      were in immune and nervous system tissues. By comparing responses in captive and
      wild birds, we found that sublethal effects of mercury were detected at lower
      levels in captive than in wild birds, probably due to the reduced sources of
      variation characteristic of the highly controlled laboratory study. Conversely,
      thresholds for more severe changes (death, disease) occurred at lower
      concentrations in wild birds than in captive birds, probably because wild birds
      were exposed to multiple stressors. Thus caution should be used in applying
      lowest observed effect levels between captive and wild studies.

PMID- 10941728
TI  - Hematologic and serum chemistry values of the captive European wildcat.
AB  - Hematologic and serum chemistry values were determined for 20 adult captive
      European wildcats (Felis silvestris) in Lleida (Catalonia, Spain). Seven wildcats
      (4 females and 3 males) were captured in the wild and 13 (4 females and 9 males)
      were born and raised in captivity. Samples were collected between September and
      December from 1993 to 1998. Blood was obtained by jugular venipuncture after
      administration of either ketamine and xylazine or ketamine and medetomidine.
      Females had significantly higher mean eosinophil counts, albumin concentration,
      (and A/G ratio) and lower mature neutrophil counts, although these differences
      were not clinically relevant. Results for many of the blood parameters fall
      within the reference range for domestic cats. Mean values for alanine
      aminotransferase, aspartate aminotransferase, creatine phosphokinase, and lactate
      dehydrogenase activities as well as blood urea nitrogen, glucose, and sodium
      concentrations were higher than the upper limit of the reference range for
      domestic cats.

PMID- 10941727
TI  - The effect of dietary aflatoxin on wild turkey poults.
AB  - Aflatoxins, toxic metabolites of Aspergillus flavus or Aspergillus parasiticus,
      cause poor feed utilization, decreased weight gains, depressed immune function,
      liver dysfunction, coagulation abnormalities, and death in a wide variety of
      species including humans. Conservationists have become concerned that
      increasingly popular wildlife feeding or baiting practices could expose wildlife
      to toxic amounts of aflatoxin-contaminated grains. In particular, the effects of
      aflatoxins on the wild turkey (Meleagris gallopova silvestris) are of concern
      because the conspecific domestic turkey is highly susceptible to aflatoxins. To
      evaluate the effect of dietary aflatoxin on wild turkeys, four groups of 4-mo-old
      wild turkeys were fed diets containing either 0, 100, 200, or 400 micrograms
      aflatoxin/kg feed for 2 wk in September and October 1996. Aflatoxin-fed poults
      had decreased feed consumption and weight gains as compared with control poults.
      Decreased liver-to-body weight ratios, liver enzyme alterations, slightly altered
      blood coagulation patterns, and mild histologic changes indicated low-level liver
      damage. Compromise of cell-mediated immunity was indicated by decreased
      lymphoblast transformation. The effects were apparent in all treatment groups to
      variable levels, but significant differences most often were found at 400
      micrograms aflatoxin/kg feed. This study shows that short-term aflatoxin
      ingestion by wild turkeys can induce undesirable physiologic changes; therefore,
      exposure of wild turkeys to feeds containing aflatoxin levels of 100 micrograms
      aflatoxin/kg feed or more should be avoided.

PMID- 10941729
TI  - Evaluation of zuclopenthixol acetate to decrease handling stress in wapiti.
AB  - Handling stress and capture myopathy are important consequences of intensively
      managing wildlife species. Over the last 15 yr, the use of long-acting
      neuroleptic (LAN) drugs in wildlife has increased, and these drugs have become a
      valuable tool for decreasing capture and handling stress in many species. At this
      time, reports on the use of these drugs in North American species are limited.
      The major objective of this study was to evaluate the use of the LAN,
      zuclopenthixol acetate (Clopixol-Acuphase), to decrease both quantifiable and
      subjective measurements of stress and activity in wild wapiti (Cervus elaphus,
      North American elk). This blinded, randomized study took place in February 1999
      in Manitoba (Canada) and involved 11 animals receiving the drug and 12 animals
      acting as controls. At 24 hr after drug administration, there were measurable and
      significant decreases in the stress and activity of treated animals versus
      controls during handling. Treated animals had significantly lower mean body
      temperatures (39.0 versus 40.6 C), less hemoconcentration (mean packed cell
      volume 0.42 versus 0.49, mean hemoglobin 159.09 versus 181.75 g/L, mean total
      protein 65.0 versus 70.25 g/L), lower mean serum cortisol (97.91 versus 139.50
      mmol/L), lower mean blood lactate (3.39 versus 5.98 mmol/L), and were less
      metabolically acidotic (mean pHv 7.45 versus 7.34, mean bicarbonate 29.36 versus
      24.25 mmol/L, mean base excess 5.64 versus -0.83 mmol/L). Only control animals
      had evidence of muscle damage based on serum biochemistry (creatine phosphate
      values of two animals of 42,080 and 25,887 U/L). No animals developed clinical
      capture myopathy, and no animals died. Measurable effects of this drug were still
      apparent at 72 hr post-administration. The results of this study support the use
      of Clopixol-Acuphase in wapiti as a means to decrease handling stress and
      activity.

PMID- 10941730
TI  - Microbes in tree swallow semen.
AB  - A frequently hypothesized but poorly studied cost of multiple mating in birds is
      that exposure to pathogenic sexually transmitted microbes (STM's) can lower
      reproductive success. Conversely, female birds may benefit from high frequencies
      of copulation and multiple copulation partners if they receive cloacal
      inoculations of beneficial STM's that can either protect them against future
      encounters with pathogens and/or serve as therapy against present infection. We
      examined the semen of 30 male tree swallows (Tachycineta bicolor) in 1998 to
      determine the presence and prevalence of potential pathogenic and beneficial
      STM's. Semen was collected directly from males after applying gentle pressure to
      the cloaca and we used standard microbiological techniques to identify microbes.
      We found that 19 of 30 samples contained one or more types of microbes. In these
      19 positive samples, we isolated both pathogenic and beneficial microbes from 11,
      only pathogenic microbes from seven, and only beneficial microbes from one. This
      variation among males suggests that females would benefit from considering a
      particular male's potential as a donor of either pathogenic or beneficial STM's
      as a criterion for mate choice. There were few significant differences between
      males with pathogen-infected semen and those without pathogens in their semen in
      measures of size, morphology, and ectoparasite score and feather damage.
      Likewise, there were few significant differences between males with beneficial
      Lactobacilli spp. in their semen and those without Lactobacilli spp. in their
      semen in measures of size, morphology, and ectoparasite score and feather damage.
      We were unable to determine if there was a relationship between microbe presence
      and prevalence on reproductive performance.

PMID- 10941731
TI  - Validation of the fluorescence polarization assay and comparison to other
      serological assays for the detection of serum antibodies to Brucella abortus in
      bison.
AB  - A number of serological tests were compared for the detection of antibodies to
      Brucella abortus in bison (Bison bison). The performance of the fluorescence
      polarization assay (FPA) in both the preliminary evaluation and a subsequent
      blind validation indicated that this test was the most suitable for serological
      diagnosis of brucellosis in bison. The sensitivity and specificity in the
      preliminary evaluation were 92.1% and 99.4%, respectively. The sensitivity and
      specificity in a subsequent blind study were 96.3% and 97.6%, respectively. In a
      double blind study conducted on bison vaccinated with B. abortus strain 19, the
      data suggests that the FPA can differentiate bison infected with B. abortus from
      bison vaccinated with B. abortus strain 19. Both the indirect immunoassay
      (IELISA) and the competitive immunoassay (CELISA) performed nearly as well as the
      FPA. The buffered antigen plate agglutination test (BPAT) and the complement
      fixation test (CFT) did not perform as well as the FPA, CELISA or the IELISA in
      both studies. The FPA is a homogeneous assay eliminating the washing steps and
      reducing incubation to minutes rather than hours saving on time, equipment,
      materials, reagents and cost. These attributes, together, with its excellent
      sensitivity and specificity make the FPA an attractive test for the detection of
      serum antibodies to Brucella abortus in bison.

PMID- 10941732
TI  - Safety and efficacy of Brucella abortus strain RB51 vaccine in captive pregnant
      elk.
AB  - Brucella abortus strain RB51 is a laboratory-derived rough mutant of virulent B.
      abortus strain 2308 used as a vaccine because it induces antibodies that do not
      react on standard brucellosis serologic tests. Strain RB51 vaccine was evaluated
      in pregnant captive elk (Cervus elaphus) to determine (1) if it induced abortion
      and (2) if it protected against abortion following subsequent challenge. The time
      period of this study (February-June, 1998) was similar to field conditions where
      elk are vaccinated and possibly exposed to B. abortus. Fourteen elk were randomly
      and equally divided into vaccinated and control groups. The vaccinated group was
      vaccinated intramuscularly with 1.03 x 10(10) colony-forming units (CFU) of
      strain RB51 and seroconverted postvaccination. Antibodies to strain RB51 were
      detected by a modification of an existing dot-blot assay. Both groups were
      challenged 40 days postvaccination with 9.8 x 10(6) CFU of B. abortus strain 2308
      administered intraconjunctivally. The first abortion occurred 38 days
      postchallenge. Abortion occurred in all control elk and in five of seven
      vaccinated elk 5 to 12 wk postchallenge (P = 0.23). Mixed strain RB51 and 2308
      infections were present in fetuses and vaginas from the vaccinated group whereas
      only strain 2308 was cultured from control group fetuses and vaginal swabs.
      Further evaluation of strain RB51 will be necessary to determine if it will be
      safe and efficacious in free-ranging pregnant elk.

PMID- 10941733
TI  - Safety of Brucella abortus strain RB51 in bull elk.
AB  - Some of the elk (Cervus elaphus nelsoni) of the Greater Yellowstone Area
      (Wyoming, Idaho, Montana; USA) are infected with Brucella abortus, the bacterium
      that causes bovine brucellosis. Brucella abortus strain RB51 vaccine is being
      considered as a means to control B. abortus induced abortions in cow elk.
      However, the most probable vaccination strategies for use in free-ranging elk
      might also result in some bull elk being inoculated, thus, it is important to
      insure that the vaccine is safe in these animals. In the winter of 1995, 10 free
      ranging bull elk calves were captured, tested for B. abortus antibodies, and
      intramuscularly inoculated with 1.0 x 10(9) colony forming units (CFU) of B.
      abortus strain RB51. Blood was collected for hemoculture and serology every 2 wk
      after inoculation for 14 wk. Beginning 4 mo postinoculation and continuing until
      10 mo postinoculation elk were serially euthanized, necropsied, and tissues
      collected for culture and histopathology. These elk cleared the organism from the
      blood within 6 wk and from all tissues within 10 mo. No lesions attributable to
      B. abortus were found grossly and only minimal to mild lymphoplasmacytic
      epididymitis was found in a few elk on histologic examination. In a separate
      study, six adult bull elk from Wind Cave National Park (South Dakota, USA) were
      taken to a ranch near Carrington (North Dakota, USA). Three were orally
      inoculated with approximately 1.0 x 10(10) CFU of RB51 and three were inoculated
      with corn syrup and saline. Ninety days post-inoculation semen was examined and
      cultured from these bulls. Strain RB51 was not cultured from their semen at that
      time. There were no palpable abnormalities in the genital tract and all elk
      produced viable sperm. Although they contain small sample sizes, these studies
      suggest that B. abortus strain RB51 is safe in bull elk.

PMID- 10941734
TI  - Efficacy of a type C botulism vaccine in green-winged teal.
AB  - We tested the efficacy of a single dose of Botumink toxoid for protecting wild
      green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium
      botulinum type C. We challenged control and immunized ducks with four different
      doses of type C botulinum toxin to determine the LD50 for this species and to
      evaluate vaccine protection. Fewer immunized ducks were affected with botulism
      than control ducks, indicating that a single dose of Botumink toxoid could
      increase the survival of ducks during epizootics. However, the frequency of
      immunized ducks with signs of botulism increased with the challenge dose of
      botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green
      winged teal LD50, about 50% of the immunized ducks were affected. We believe an
      improved vaccine or a better delivery system is required to justify immunization
      of wild birds for experimental survival studies.

PMID- 10941735
TI  - Serologic and molecular evidence of Ehrlichia spp. in coyotes in California.
AB  - In order to determine the role of coyotes in the epidemiology of granulocytic and
      monocytic ehrlichial agents in California (USA), we tested 149 serum samples for
      antibodies against Ehrlichia equi, E. risticii, and E. canis, using an indirect
      immunofluorescent antibody test. Polymerase chain reaction (PCR) assay was used
      to survey for the presence of members of the E. phagocytophila genogroup, E.
      risticii and E. canis in blood samples of 95 coyotes. Sixty-eight (46%) samples
      were seropositive for E. equi, two (1%) for E. risticii and none of the samples
      had antibodies reactive to E. canis. Two and one coyote were positive for E.
      risticii and members of the E. phagocytophila genogroup by PCR assay,
      respectively. In contrast, the 95 samples were negative for E. canis by PCR.
      Ninety-five percent of the 68 E. equi seropositive coyotes and the one coyote PCR
      positive for members of the E. phagocytophila genogroup originated from a coastal
      area. However, the two E. risticii seropositive coyotes and the two coyotes PCR
      positive for E. risticii were from northern California. Sequence analysis of the
      three amplified PCR products revealed the agent to be similar in two coyotes to
      the sequences of E. risticii from horses originating from northern California and
      identical in one coyote to the agent of human granulocytic ehrlichiosis and E.
      equi from California. Thus, coyotes are exposed to granulocytic ehrlichiae and E.
      risticii and may play a role in the epidemiology of these ehrlichial agents in
      California.

PMID- 10941736
TI  - Epizootic vesicular disease in captive California sea lions.
AB  - An epizootic of vesicular disease occurred in a group of semi-domesticated
      California sea lions (Zalophus californianus) during the months of April and May
      1997. Ten castrated mature male sea lions, ages 12 to 19 yr, were housed in three
      adjacent open-ocean net enclosures in San Diego Bay (California, USA). Four
      animals (40%) developed oral and extremity vesicles, anorexia, and were reluctant
      to perform learned behaviors. One animal developed vesicles but maintained a
      normal appetite and behavior. The remaining animals showed no clinical signs of
      infection. Virus (designated FADDL 7005) was isolated from four of the five
      animals that developed vesicles. Serum antibody titers to FADDL 7005, a
      previously untyped calicivirus, were demonstrated in animals that showed any
      combination of clinical signs and in two animals that did not show any clinical
      signs. No virus was isolated from five fecal samples collected from four of the
      group animals. Clinical signs lasted 4 to 20 days in affected animals. All
      affected animals recovered from infection. An experimental swine was inoculated
      with FADDL 7005 and developed vesicular disease, which was transmitted to another
      experimental swine upon contact. It is proposed that FADDL 7005 is a new San
      Miguel sea lion virus.

PMID- 10941737
TI  - A morbillivirus antibody survey of Atlantic walrus, narwhal and beluga in Canada.
AB  - A longitudinal serologic survey was conducted for morbillivirus antibodies in
      Atlantic walruses (Odobenus rosmarus rosmarus), narwhal (Monodon monoceros), and
      beluga (Delphinapterus leucas) from the Northwest Territories, Nunavut and the
      St. Lawrence estuary (Canada). Sixty-five of 131 (50%) walruses sampled between
      1984 and 1993 had detectable morbillivirus neutralizing antibodies. Positive
      walrus were identified from four of five Arctic sampling sites, to as far back as
      1984. Prevalence of morbillivirus neutralizing antibodies in walruses from Foxe
      Basin ranged from a high of 76% (n = 21) in 1993 to a low of 22% (n = 28) in
      1984. Limitations in sample acquisition may have produced underestimates for the
      1984 data. There are no reports of clinical morbillivirus infection in walruses.
      Our results are consistent with the hypothesis that a morbillivirus similar or
      identical to phocine distemper virus (PDV) has circulated among walrus
      populations of the eastern Canadian Arctic, at least since the early 1980s. No
      narwhal (n = 79) or beluga (n = 445) from Arctic waters were identified as having
      antibodies to dolphin morbilivirus (DMV) above the threshold serum dilution of
      log2 4. Also, none of the beach-cast cetacean carcasses (n = 28) from the Gulf of
      St. Lawrence and the St. Lawrence estuary were positive for antibodies to DMV.
      This indicates that Gulf of St. Lawrence, St. Lawrence estuary, and Arctic
      cetaceans either have not been exposed to DMV or an antigenically related
      morbillivirus, or are not susceptible to infection.

PMID- 10941738
TI  - Antigenic, phenotypic and molecular characterization confirms Babesia odocoilei
      isolated from three cervids.
AB  - Babesia isolates from an elk (Cervus elaphus canadensis) and a caribou (Rangifer
      tarandus caribou) with fatal infections were compared to Babesia odocoilei
      (Engeling isolate) from white-tailed deer (Odocoileus virginianus) by
      experimental infection, serologic, and small subunit ribosomal RNA (SSU rRNA)
      gene sequence analysis studies. Both the indirect fluorescent antibody test and
      immunoprecipitation assays demonstrated antigenic variation among the isolates.
      Experimental infection studies showed no clinical differences among the isolates.
      Nucleotide sequence analysis showed that the elk and caribou Babesia sp. isolates
      possessed SSU rRNA genes with identical sequences to that of B. odocoilei. A
      phylogenetic tree constructed from SSU rRNA gene sequences shows that B.
      odocoilei is most closely related to Babesia divergens, both of which branch
      together in the true babesia clade.

PMID- 10941739
TI  - Sylvatic trichinellosis in southwestern Spain.
AB  - The epidemiology of Trichinella spp. in their main sylvatic hosts, wild boar (Sus
      scrofa ferus and red fox (Vulpes vulpes), in Extremadura (southwestern Spain) was
      studied. We examined 88 Trichinella spp.-positive wild boar muscle-tissue samples
      from a total of 29,333 killed animals, referred to the Veterinary Parasitology
      Department (University of Extremadura, Spain) by the Extremadura Veterinary
      Service. Additionally, 227 red foxes killed during the hunting season and thus
      not subject to veterinary controls were examined for trichinellosis. Trichinella
      spp. larvae were found in six (3%) of the red foxes. All samples were examined
      using direct diagnostic techniques, including trichinoscopy and artificial
      digestion. The mean intensity of infection was 74.8 larvae/g (LPG) of muscle
      tissue in wild boars, compared to 30.6 LPG in foxes. Trichinella spiralis (sensu
      stricto) predominated over T. britovi in wild boars. Random amplified polymorphic
      DNA (RAPD) and alloenzyme typing showed that 74% of infected wild boars had only
      T. spiralis, 21% had only T. britovi, and 5% showed mixed infections. In
      contrast, 33% of infected foxes were infected only with T. spiralis, while 67%
      had T. britovi, suggesting a clear predominance of the latter in foxes. We
      suspect the existence of a paranthropic or sylvatic cycle in large areas of this
      region; given the ease of transfer between sylvatic and domestic or semi-domestic
      animals, this implies a high epidemiological risk.

PMID- 10941740
TI  - Use of a two-step Percoll gradient for separation of loggerhead sea turtle
      peripheral blood mononuclear cells.
AB  - In order to determine a suitable procedure for isolating peripheral blood
      mononuclear cells (PBMCs) from loggerhead sea turtles (Caretta caretta), blood
      was collected using three different anticoagulants (sodium heparin, sodium
      citrate or potassium EDTA) and separated using a single step commercially
      prepared arabinogalactan gradient of 1.077 g/ml density or multiple step Percoll
      gradients between 1.053 and 1.076 g/ml density (40-60% stock isotonic Percoll
      suspension). Heparinized blood centrifuged over a two-step 45/55% (1.059/1.070
      g/ml) Percoll gradient yielded 99 to 100% mononuclear cells at the 45/55%
      interface. Mononuclear cell viability ranged from 85 to 97% with cell yields up
      to 9.2 x 10(6) cells/mL. An unexpected finding was a population of low density
      granulocytes migrating to 40% (1.053 g/ml) and 45% Percoll layers in the multiple
      step gradients. These granulocytes could be eliminated from the PBMC preparation
      by use of the two-step 45/55% Percoll gradient. Isolated PBMCs can be used for
      cellular immunology and toxicology studies on these threatened marine organisms
      for which other tissues can usually be obtained only sporadically from post
      mortem specimens.

PMID- 10941741
TI  - Blood plasma chemistries from wild mourning doves held in captivity.
AB  - Despite the extensive amount of research conducted on mourning doves (Zenaida
      macroura), no biochemical reference values exist for this species. Our objective,
      therefore, was to establish base line clinical chemistry reference values for
      mourning doves to assist with establishing clinical diagnoses. Wild mourning
      doves were captured 19 March 1996 to 8 August 1996, and 6 February 1998 to 12 May
      1998; blood samples were collected from 382 mourning doves. Plasma biochemical
      values were established for glucose, sodium, potassium, chloride, enzymatic CO2,
      albumin, total protein, globulin, calcium, phosphorus, cholesterol, magnesium,
      aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lactate
      dehydrogenase (LDH), and uric acid. These reference values are invaluable for
      determining diagnosis of diseases of the gastrointestinal, hepatic, renal,
      cardiovascular, musculoskeletal, and endocrine systems.

PMID- 10941742
TI  - Immobilization of wild ocelots with tiletamine and zolazepam in southern Texas.
AB  - Telazol was used to immobilize nine wild ocelots (Leopardus pardalis) captured in
      box-traps in southern Texas (USA) between May 1997 and April 1998. Mean (+/- SD)
      intramuscular dosage rate of 5.05 (+/- 0.76) mg/kg produced an induction time of
      3.7 +/- 1.8 min. Duration of cataleptic anesthesia was 67.4 +/- 19.8 min and
      ocelots stood 50.0 +/- 30.7 min after emergence from cataleptic anesthesia.
      Ocelots recovered to their preinjection condition 129.7 +/- 28.8 min after first
      standing and 250.8 +/- 55.1 min after initial injection. We observed no adverse
      reactions to Telazol aside from minor loss of thermoregulatory control. Telazol
      administered at 5 mg/kg was an effective and safe immobilizing agent for wild
      ocelots.

PMID- 10941743
TI  - Survival of Trichomonas gallinae in white-winged dove carcasses.
AB  - Survival of Trichomonas gallinae was examined in white-winged dove (Zenaida
      asiatica) carcasses to assess whether birds that have been dead up to 8 hr can be
      sampled reliably for this protozoan. Carcasses of 100 T. gallinae-positive white
      winged doves were separated into four groups of 25 birds, representing 2, 4, 6,
      and 8 hr post mortem sampling intervals and placed into an environmental chamber
      maintained at 27 C and 75% relative humidity. Live T. gallinae were isolated in
      96, 100, 100, and 92% of the carcasses at each of the respective post mortem
      intervals. The experiment was repeated with another 100 carcasses of T. gallinae
      positive white-winged doves placed in the environmental chamber, this time
      maintained at 27 C and 40% relative humidity. Live T. gallinae occurred in 96,
      100, 96, and 100% of the carcasses at each of the respective post mortem
      intervals. Across both trials, the overall ability to detect positive birds from
      sampling carcasses up to 8 hrs post mortem was 97%. An a posteriori experiment
      was conducted in which 23 and 18 carcasses from the second trial were maintained
      in the environmental chamber at 27 C and 40% relative humidity and resampled at
      24 and 48 hr post mortem, respectively. Live trichomonads were isolated from 91
      and 44% of the carcasses at 24 and 48 hr, respectively. Results suggest live T.
      gallinae can be obtained from dove carcasses reliably up to 8 hr and possibly up
      to 24 hr after host death. The ability for T. gallinae to survive within this
      time interval can aid wildlife personnel in monitoring this protozoan at hunter
      check stations or obtaining samples from recently killed birds.

PMID- 10941744
TI  - Evaluation of host preferences by helminths and ectoparasites among black-tailed
      jackrabbits in northern California.
AB  - Fifty-four black-tailed jackrabbits (Lepus californicus) (five juvenile males, 22
      adult males, five juvenile females, and 22 adult females) from Humboldt County,
      California (USA) were evaluated for sex and age-specific differences in parasite
      prevalences and intensities, 26 February through 30 October 1996. Nematodes found
      included Biogastranema leporis in 42 hares (78% prevalence), Rauschia
      triangularis in 26 hares (48%), Trichostrongylus calcaratus in 14 hares (26%),
      and Trichuris sylvilagi in two hares (4%). Cestodes found included Taenia sp.
      cysticerci in five hares (9%) and Taenia sp. coenurus found in one hare (2%).
      Ectoparasites found included the ticks Dermacentor variabilis on 10 hares (19%)
      and Ixodes spinipalpis (= Ixodes neotomae) on nine hares (17%), as well as the
      anoplurid louse Haemodipsus setoni on 12 hares (22%). No significant differences
      in the parasite prevalences or intensities were found between male and female
      jackrabbits; this was for all males and females collectively, juvenile males and
      females only, as well as adult males and females only. Combining male and female
      hosts, adult jackrabbits had a significantly higher prevalence of B. leporis and
      R. triangularis compared to juveniles. This is the first known report of
      Trichostrongylus calcaratus, Rauschia triangularis, Trichuris sylvilagi, and
      Dermacentor variabilis among black-tailed jackrabbits and the first known report
      of T. calcaratus and T. sylvilagi in the western USA. This is the first published
      report of I. spinipalpis, the vector for Lyme disease in California, on black
      tailed jackrabbits.

PMID- 10941745
TI  - Strigea falconispalumbi in Eurasian buzzards from Germany.
AB  - Eighty-three free-living Eurasian buzzards (Buteo buteo) from three different
      areas in Germany were examined for adult stages and the metacercaria of the
      trematode Strigea falconispalumbi. Prevalences of adult parasites in the small
      intestine was 36% (Berlin/Brandenburg), 28% (Lower Saxony) and 3% (Baden
      Wurttemberg). Metacercaria in the connective tissue of the neck were found in
      58%, 55%, and 10% of birds from the respective areas. Significant differences in
      the prevalence of S. falconispalumbi adults and metacercaria between the areas
      were attributed to the different abundance of freshwater which is the key habitat
      for two intermediate hosts.

PMID- 10941746
TI  - Parelaphostrongyliasis in white-tailed deer in Missouri.
AB  - The heads of 137 white-tailed deer (Odocoileus virginianus) were collected on the
      opening day of the 1996 Missouri (USA) fire-arms deer season and surveyed for the
      presence of meningeal worm (Parelaphostrongylus tenuis). Eighteen percent of the
      deer examined were infected. Mean intensity of infection was 2.0 (range 1-7).
      There were no significant differences of infection or mean intensity when deer
      were classified and compared according to sex or age class.

PMID- 10941747
TI  - Gastric intramural hematoma and hemoperitoneum in a captive northern fur seal.
AB  - A 16-yr-old adult male northern fur seal (Callorhinus ursinus) was found dead in
      its outdoor pool in November 1995. The animal was maintained at Mystic Aquarium
      (Mystic, Connecticut, USA) from March 1980 to November 1995. Gross necropsy
      findings included hemoperitoneum and locally extensive gastric intramural
      hemorrhage that involved the posterior fundic, antral, and pyloric regions and
      extended into the duodenum. The gastric mural thickening grossly resembled
      hemangioma, and the gastric serosa was ruptured at the site of maximal mural
      expansion. In histologic sections of the stomach, a cribiform network of fibrin,
      which encompassed numerous variably-sized aggregates of closely packed
      erythrocytes, markedly expanded the submucosa. No vascular endothelium was
      identified in serial histologic sections of the expanded gastric submucosa
      stained with hematoxylin and eosin or immunohistochemically with antibodies to
      vimentin and Factor VIII-related antigen, establishing an absence of hemangioma.
      Carstairs' and Weigert's histochemical stains confirmed that the framework
      expanding the submucosa was fibrin. Although the appearance of the gastric wall
      resembled hemangioma, a population of neoplastic endothelial cells was not
      identified within the submucosal expansion of hemorrhage and fibrin, and
      microscopic evidence was most consistent with the diagnosis of gastric intramural
      hematoma. This lesion is a rare pathologic event that has not been reported in
      marine mammals, but one that should be included in diagnostic considerations of
      hemoperitoneum and gastric mural expansion.

PMID- 10941748
TI  - Sarcoma of possible nerve sheath origin in a captive muskrat.
AB  - A captive adult female muskrat (Ondatra zibethicus) was found dead without
      previous signs of disease. At necropsy, abdominal organs were infiltrated with a
      poorly demarcated, soft, tan tissue. Microscopically this tissue was composed of
      neoplastic cells assuming two distinct growth characteristics consistent with
      Antoni A and B patterns. Ultrastructurally, the neoplastic cells were
      pleomorphic, lacked junctional devices, had abundant mitochondria and
      ergastoplasm, and frequently were closely associated with extracellular collagen.
      Immunocytochemical examination of tumor cells demonstrated sporadic expression of
      neuron specific enolase. Microscopic tumor metastases to the myocardium,
      ascending aorta, lungs and visceral pleura were present. This is the first report
      of a sarcoma compatible with a malignant peripheral nerve sheath tumor in a
      muskrat.

PMID- 10941749
TI  - Absence of antibodies against canine distemper virus in free-ranging populations
      of the Eurasian badger in Great Britain.
AB  - Canine distemper virus (CDV) is a serious disease of wild carnivores throughout
      the world. In Europe, infection has been detected in several carnivores including
      the Eurasian badger (Meles meles). In the present study 182 badger blood samples
      were collected from an intensively studied population of wild badgers in
      southwestern England (January-July, 1997), and a further 286 from throughout
      southern Britain (June 1996-November 1998). A neutralizing peroxidase-linked
      antibody test was used for the detection of antibodies against CDV. All the
      samples were negative for CDV antibodies, suggesting that in contrast to mainland
      Europe, the disease may be either absent or maintained at low levels in British
      badgers.

PMID- 10941750
TI  - First report of myxomatosis in Mexico.
AB  - An outbreak of myxomatosis occurred between September and October 1993 on a
      rabbit farm in Punta Colnett (Ensenada, Baja California in northwestern Mexico,
      Transpeninsular Highway, km 128) and was confirmed by the Mexico-USA Commission
      for Prevention of Foreign Diseases of Animals (CPA). This represents the first
      officially confirmed case of the disease in Mexico. Like the cases in California
      (USA), the brush rabbit (Sylvilagus bachmani) seems to be the carrier of the
      virus, since serum samples from wild rabbits from different areas of the
      peninsula of Baja California were found to contain antibodies against the myxoma
      virus.

PMID- 10941751
TI  - Bovine virus diarrhea virus in free-living deer from Denmark.
AB  - Free-living deer are suggested as a possible source of infection of cattle with
      bovine virus diarrhea (BVD) virus. To examine this hypothesis blood samples from
      476 free-living deer were collected during two different periods and tested for
      BVD virus and antibody in Denmark. In 1995-96, 207 animals were tested. These
      included 149 roe deer (Capreolus capreolus), 29 fallow deer (Dama dama), 20 red
      deer (Cervus elaphus) and one sika deer (Cervus sika). For the remaining eight
      animals no species information was available. In 1998-99, 269 animals were tested
      including 212 roe deer and 57 red deer. The animals were selected from areas with
      a relatively high prevalence of cattle herds with a BVD persistent infection
      status in 1997 and 1998. All 207 samples from 1995-96 were found antibody
      negative except two samples from red deer. Only 158 of the 207 samples were
      tested for virus and were all found negative. Of the 269 samples from 1998-99 all
      but one were antibody negative. The positive sample was from a red deer. All
      samples were virus-negative. It appears that BVD infection does not occur in roe
      deer in Denmark. The presence of antibody in a few red deer from various
      districts in Jutland probably results from cattle to deer transmission, rather
      than spread among deer. Hence, the possibility of free-living deer as a source of
      infection for cattle in Denmark seems to be remote.

PMID- 10941752
TI  - An epizootic of hemorrhagic disease in white-tailed deer in Missouri.
AB  - As part of a white-tailed deer (Odocoileus virginianus) survival study in
      Missouri (USA) we were actively monitoring 97 radio-collared deer when 8 (8%)
      died. This mortality, which occurred from 20 August to 23 September 1996,
      consisted of five adult females, two yearling females and one yearling male.
      Based on the seasonality of this mortality and the isolation of epizootic
      hemorrhagic disease virus (EHDV) serotype 2 from one of these animals, we believe
      that these losses resulted from an epizootic of hemorrhagic disease. The remains
      of five unmarked deer that may have died from HD also were found on the study
      area during this same period. During the fall following this mortality, we tested
      serum from 96 deer taken by hunters in the immediate area. Fifteen (16%) were
      positive for EHDV or bluetongue virus (BTV) antibodies as determined by agar gel
      immunodiffusion tests. Serum neutralization test results indicated that previous
      infections were caused by EHDV virus serotype 2. Based on these data, and
      assuming that there was no prior exposure to EHDV serotype 2 in this population,
      the exposure rate for this epizootic was 24% of which 8% died. We noted hoof
      interruptions in only two of the 96 deer sampled. During this mortality event,
      the Missouri Department of Conservation received no reports of dead deer, and
      without the radio-monitored animals the event would have been undetected.

PMID- 10941753
TI  - Attempted transmission of Ehrlichia chaffeensis among white-tailed deer by
      Amblyomma maculatum.
AB  - A deer was needle-exposed intravenously to Ehrlichia chaffeensis (Rickettsiales:
      Ehrlichieae) in canine macrophage (DH82) cells and 7 days later was infested with
      laboratory-reared Amblyomma maculatum (Koch) (Acari:Ixodidae) nymphs for
      acquisition feeding. After molting, the adult ticks were allowed to feed on a
      naive deer. The organism was reisolated from the needle-exposed deer by cell
      culture and E. chaffeensis DNA was detected in the deer's blood by PCR. Similar
      isolation/recovery techniques were used for the tick-exposed deer and no evidence
      of infection was found. Although these findings must be considered as preliminary
      owing to inadequate controls, the data suggest that A. maculatum is probably not
      a suitable vector for E. chaffeensis.

PMID- 10941754
TI  - Brucellosis in ringed seals and harp seals from Canada. lforbes@em.agr.ca.
AB  - A novel Brucella sp. was isolated from lymph nodes of four ringed seals (Phoca
      hispida) collected near Pangnirtung (Baffin Island, Canada) in January and
      February 1995 and in one harp seal (Phoca groenlandica) collected near the
      Magdalen Islands (Gulf of St. Lawrence, Canada) in March 1996. Bacteriological
      characteristics were the same for all five isolates. The colonies were typical of
      Brucella spp., but took 2 to 5 days longer than the traditional species to appear
      on primary isolation media. Biotyping results did not match any of the known
      biovars of Brucella, but were similar to isolates of the genus Brucella
      previously reported from marine mammals inhabiting other areas of the northern
      hemisphere. This is the first confirmed report of brucellosis in marine mammals
      from Canada, and the first report of this organism in ringed and harp seals.

PMID- 10941755
TI  - State of the Journal: 2000.

PMID- 10941757
TI  - An examination of state Medicaid financing arrangements for early childhood
      development services.
AB  - OBJECTIVE: To determine the extent to which Medicaid finances early childhood
      development services, either on a capitated or fee-for-service basis, and to
      gauge future interest in financing such services. METHODS: We analyzed state
      Medicaid managed care contracts in effect in April 1998 in 45 states using
      capitated arrangements for children at the end of 1997 to ascertain whether state
      Medicaid agencies financed any of six types of early childhood development
      services, including parent counseling, home visiting, comprehensive assessments,
      telephone advice lines, parent education classes, and case management. We also
      conducted structured telephone surveys with the same 45 states' Medicaid managed
      care directors. RESULTS: Overall, state Medicaid agencies finance few early
      childhood development services on a capitated or fee-for-service basis. Case
      management was the most popular service to be paid for fee-for-service. Parent
      education was the most popular service required in managed care contracts. Parent
      counseling and telephone advice lines for information on child development or
      parenting issues were the services least likely to be reimbursed through either
      Medicaid financing mechanism. CONCLUSION: To date, Medicaid agencies generally
      have not required managed care plans to cover early childhood development
      services, nor have they paid for such services on a fee-for-service basis.
      However, 17 states expressed an interest in expanding early childhood development
      services, particularly home visiting, parent education, and telephone advice
      lines. Nonetheless, several challenges exist in expanding Medicaid financing,
      including the need for more evidence on cost-effectiveness and greater political
      support for promoting early childhood development.

PMID- 10941756
TI  - Use of high-technology care among women with high-risk pregnancies in the United
      States.
AB  - OBJECTIVE: Infant mortality has been reduced dramatically with the development of
      perinatal regionalized high-technology care. Our objective was to assess use of
      high technology care among women with high-risk pregnancies in the urban and
      rural United States. METHODS: The 1988 National Maternal and Infant Health Survey
      was linked to the 1988 American Hospital Association survey of all obstetrical
      hospitals. Hospitals were classified into five levels of care based on services
      and staffing. Women were classified as having high-risk pregnancies using two
      definitions: (1) gestational age < 34 weeks and birthweight < 1500 g (High Risk
      I) and (2) the first definition or an antenatal high-risk medical diagnoses (High
      Risk II). Analyses assessed the proportion of high-risk women delivering in
      appropriate locations in the rural and urban United States and explored how
      personal characteristics, insurance status, and use and source of prenatal care
      influenced where high-risk women delivered. RESULTS: 71.2% of High Risk I and
      55.9% of High Risk II women delivered in a high-technology facility (Level IIA or
      III). Fifty percent of HRI rural women delivered in tertiary high-technology
      hospitals and 39% of HRII rural women delivered in a high-technology hospital.
      High-risk urban women were two to three times more likely to deliver in a high
      technology facility compared to their rural counterparts. The multivariate
      analysis showed that Black high-risk women were more likely to deliver in a high
      technology setting and that receipt of prenatal care in a private setting lowered
      the odds of delivering in a high-technology setting when other factors were
      controlled. CONCLUSIONS: In an era where regionalized perinatal care was not
      threatened by managed care, a large proportion of high-risk women received care
      in less than optimal settings. Rural high-risk women delivered in high-technology
      hospitals less often than their urban counterparts. The multivariate analyses
      implied that the potential barriers to care may be more important among those
      considered more socially advantaged, who may be more at the mercy of managed
      care. The current reimbursement environment, which discourages referral to
      specialists and high-technology care, could result in less access today.

PMID- 10941758
TI  - Healthcare charges and use in commercially insured children enrolled in managed
      care health plans in Washington State.
AB  - OBJECTIVE: To determine the relative importance of enrollee, physician, medical
      group, and healthcare plan characteristics as determinants of healthcare use and
      expenditures in commercially insured children < 18 years of age enrolled in
      managed care health plans. We focused on the effects of age and benefit level,
      the two most important predictors of cost and utilization in our study of adults.
      METHODS: This study included 67,432 commercially insured children who were
      between 1 and 18 years of age, and were cared for by 790 primary care physicians,
      who practiced in 60 medical care groups in Washington State. Plan enrollment and
      utilization data for 1994 were linked to a survey of medical care groups
      contracting with three managed care health plans. Benefit level for each enrollee
      was defined as low, medium, or high and was based on cost sharing by the health
      plan for hospitalization, outpatient care, and emergency department services. The
      three outcome measures included estimated total per member per year charges,
      number of ambulatory visits, and hospital days. RESULTS: In multivariate
      analysis, enrollee age was the most important determinant of total charges, with
      younger children incurring higher charges and utilization. For children 5 years
      and younger, mean total per member per year charges were $617 in the low-benefit
      category and $878 in the high category (p < .0001). These differences were less
      apparent for children 6-12 years ($355 versus $420, p = .012), and were not
      statistically significant for children 13 years and older ($503 versus $552, p =
      .14). The annual number of visits increased with benefit level for children of
      all ages. CONCLUSIONS: Enrollee age and benefit level were the most important
      determinants of healthcare use and expenditures in children enrolled in managed
      care health plans.

PMID- 10941759
TI  - Measurement error in prenatal care utilization: evidence of attenuation bias in
      the estimation of impact on birth weight.
AB  - OBJECTIVE: Errors in the measurement of the timing and number of prenatal care
      visits may produce downward bias in estimates of the impact of prenatal care use
      on birth outcomes. This paper examines the extent of attenuation bias from
      measurement error in the estimation of the effect of prenatal care use on birth
      weight. METHODS: Data were analyzed from the 1980 National Natality Survey, a
      nationally representative sample of live births with information on prenatal care
      utilization from three sources: birth certificates, medical provider surveys, and
      maternal surveys. The extent of attenuation bias in estimates of the impact of
      different measures of prenatal care use on birth weight was examined by comparing
      estimates robust to measurement error (including instrumental variables) with
      ordinary least squares results. RESULTS: There is considerable disagreement in
      measures of prenatal care across the three data sources, with correlations in the
      utilization measures computed from different sources around 0.5. The results also
      show evidence of attenuation bias from measurement error in estimates of the
      impact of prenatal care on birth weight for both White and Black mothers.
      Attenuation bias was least severe for information from the birth certificate
      report of prenatal care. CONCLUSIONS: Because of measurement error, previous
      studies may have underestimated the effect of prenatal care utilization on birth
      weight. Corrected estimates, however, do not suggest that prenatal care is a
      major predictor of birth weight. In addition, part of what previous analyses have
      interpreted as adverse selection bias may in fact be attenuation bias due to
      measurement error.

PMID- 10941760
TI  - Does the Vaccines for Children program influence pediatric nurse practitioner
      referral of disadvantaged children to public vaccine clinics?
AB  - OBJECTIVE: Concerns about financial barriers to vaccination led to the creation
      of the Vaccines for Children (VFC) program, which provides free vaccines to
      states for disadvantaged children. Our objective was to understand the effect of
      free vaccine and insurance on pediatric nurse practitioners' (PNPs) likelihood of
      referring children to public vaccine clinics. Although referral from the medical
      home to public vaccine clinics is preferable to not vaccinating, there are
      disadvantages, including the potential for windows of inadequate protection and
      fragmentation of care. METHODS: A standardized survey was conducted by trained
      personnel using computer-assisted telephone interviewing. We interviewed a
      national random sample of primary care PNPs in 1997. RESULTS: In 1997, 252 of 271
      (93%) directly contacted PNPs were interviewed. The percentage of respondents
      receiving free vaccines was 82%. Among PNPs not receiving free vaccines, the
      percentages stating that they were likely to refer insured, Medicaid insured, and
      uninsured children to public vaccine clinics were 7%, 27%, and 67%, respectively.
      In contrast, among PNPs receiving free vaccines, only 46% would refer an
      uninsured child and 10% a Medicaid child. CONCLUSIONS: Most respondents received
      free vaccine supplies in 1997. Based on current PNP data and previous physician
      data, most clinicians who do not receive free vaccine supplies are likely to
      refer uninsured children to public vaccine clinics. In contrast, clinicians who
      receive free vaccine supplies are much more likely to vaccinate uninsured and
      Medicaid-insured children.

PMID- 10941761
TI  - Research trends in mother-child healthcare, 1966-1995.
AB  - OBJECTIVE: To explore trends in mother-child healthcare (MCHC) research over the
      past 30 years. METHODS: Classifications of Medline articles were made at 5-year
      intervals using Medical Subject Headings (MeSH) as classifiers. Papers were
      classified in mutually and non-mutually exclusive categories by subject (mother
      and four age groups of children) and type of research (clinical, basic,
      epidemiologic, and unclassified) and its various combinations. RESULTS: The
      number of MCHC papers increased from 34,110 in 1966 to 65,028 in 1995, but the
      proportion of all Medline articles (18-21%) was relatively stable. There were
      remarkable long-term temporal stabilities in the proportions of MCHC papers of
      mothers and the four age groups of children. Most papers dealt with child (46%)
      and adolescents (45%), and only 11% studied mother and children together.
      Regression analysis indicated that a linear increase in number of MCHC papers in
      Medline (1053/year) was represented largely by single-age and combinations of age
      children, especially adolescence. However, the slope for mother-plus-children
      papers (113/year) was substantially higher than for mothers alone (64/year).
      Clinical papers (52%) were the dominant type of MCHC research, but the
      proportions of basic and epidemiologic papers and their combinations with
      clinical papers have increased substantially in the past decade. CONCLUSIONS:
      There has been a dominance of clinical and child-related papers in MCHC research,
      which may be a reflection of restricted outlooks of specialists in the area. This
      may change soon if the tendency toward increasing numbers of basic and
      epidemiologic papers holds.

PMID- 10941762
TI  - Child care health consultation: the Connecticut experience.
AB  - OBJECTIVES: The quality of child care is of increasing national concern. Federal
      initiatives are recommending child care health consultation to promote healthy,
      safe, and developmentally appropriate care. However, few studies have
      investigated the implementation of this recommendation. The purpose of this study
      was to explore the experience of Connecticut child care center directors and
      their health consultants who were engaged in mandated, weekly, on-site health
      consultation. METHODS: One hundred Connecticut child care center directors and
      their health consultants participated in a mailed, self-administered survey. The
      centers were stratified by region and selected by random probability sampling.
      Descriptive analyses of the data examined the perspectives of both groups.
      RESULTS: Eighty-four percent of the child care center directors reported that
      health consultation visits were important or very important for the management of
      their programs. Eighty-one percent of the health consultants believed that their
      directors considered the visits important or very important. The reported tasks
      of the health consultants were consistent with regulatory requirements. Cost was
      cited as a factor that negatively influenced access to services by at least 37%
      of the director sample. Demographics of the sample, description of the role, and
      recommendations by directors and health consultants are included. CONCLUSIONS:
      Health consultation visits were highly valued among this sample as an effective
      means of promoting children's health and development in child care centers.
      Future initiatives should promote child care health consultation through
      training, infrastructure development, and funding of health consultation
      services.

PMID- 10941763
TI  - A pediatrician's view. Skin manifestations of bioterrorism.
AB  - The physician must be in contact with the local public health infrastructure as
      soon as a potential biological agent is perceived as possible. Most states are
      now setting up contingency plans and means to address these issues in a
      systematic way. This involves using local health departments, police departments,
      fire departments, National Guard units, and federal agencies such as the CDC and
      the FBI. The key component, however, is actually identifying a biological agent
      in the community and then moving quickly to isolate those who may be at risk of
      spreading the infection.

PMID- 10941764
TI  - The diagnosis and management of acne.

PMID- 10941765
TI  - Bacterial skin infections in children: the common and the not so common.

PMID- 10941766
TI  - Insect and arachnid stings, bites, infestations, and repellents.

PMID- 10941767
TI  - Making rash decisions in the diaper area.

PMID- 10941769
TI  - [We speak out: relatives of mentally ill take a stand].

PMID- 10941768
TI  - Hemangiomas: when to worry.

PMID- 10941771
TI  - [Satisfaction of relatives with the process of deinstitutionalization].
AB  - During the last eight years we arranged an extensive process of change in
      Eckardtsheim, a part of Bethel in the city of Bielefeld. As part of the process
      of deinstitutionalization we tried to change institutional needs into the needs
      for help and support of the individuals. One important part of this process was
      working with family members of our clients in a variety of intervention
      strategies. We evaluated the relatives within the concept of customer orientation
      in different viewpoints. All family members got a mailed questionnaire (n =
      1,068) in which they were questioned on their expectations and satisfaction with
      the most important aspects concerning the cooperation between family members and
      the treatment of the patients. We implemented support programs for the family
      members and asked them to judge these programs and the general process of change
      in the institution. 42% answered, mostly brothers and sisters. We received
      general support for our programs with a lot of individual criticism to certain
      parts of the process. Brothers and sisters were sceptical about
      deinstitutionalization of patients who had been institutionalized for decades.
      Working with families in these situations demands different ways of intervention,
      like information about the hospitalized family members and about the
      institutional change process as well as individualized support for the family
      members themselves. Services for the family members of long term hospitalized
      patients are extremely important and necessary for a positive outcome in the
      process of deinstitutionalization.

PMID- 10941770
TI  - [Ecologic distribution of mental disorders in urban areas. Review of six decades
      of ecologic research in psychiatry].
AB  - In 1939, Robert Faris and Warren Dunham published their pioneering work on
      "Mental disorders in urban areas". They investigated the distribution of mental
      disorders in Chicago. In the following decades, a number of studies using a
      similar design were carried out in various cities in the United States and in
      Europe, which largely replicated Faris' and Dunham's findings. The concentration
      of most psychiatric disorders in certain problem areas indicates the existence of
      a relationship between their distribution and unfavorable social conditions.
      However, the intention of ecological studies to find strong evidence for the
      psycho-social cause of mental disorders, especially of schizophrenia, failed. In
      schizophrenia, social selection leading to a particular spatial distribution of
      schizophrenic patients as a consequence of their illness or premorbid condition
      seems to be the most important factor. Rather than making a substantial
      contribution to the search for the causes of mental disorders as has been assumed
      up to now, identifying high risk areas of psychiatric disorders may serve as a
      rational basis for service planning and the allocation of resources.

PMID- 10941772
TI  - [Expectations of psychiatric patients from their outpatient and inpatient
      treatment].
AB  - OBJECTIVE: This study describes patient evaluations about treatment interventions
      and the subjective value of specific treatment expectations. METHOD: A random
      sample of 425 out-patients and in-patients was assessed to evaluate importance of
      treatment interventions and specific expectations of psychiatric treatment.
      RESULTS: Preferences regarding treatment interventions varied among diagnostic
      groups. Psychiatric patients ranked medication and supporting therapeutic
      conversations the highest. Sociodemographic characteristics, numbers of previous
      hospitalizations, quality of life and social abilities influenced treatment
      expectations. A patient's perception of dissatisfying quality of life and high
      social vulnerability increased the need for social assistance. CONCLUSION:
      Subjective treatment expectations of psychiatric patients should be the start-out
      for every treatment-regime. Socially vulnerable patients should be identified and
      specific treatment plans should be developed at treatment-start.

PMID- 10941773
TI  - [Video technology--a medium for milieu therapy?].
AB  - Video technology has been in use in the psychiatric field for more than 20 years
      for diagnostic, scientific, co-therapeutic or educational purposes. However,
      little is known of its potential applications and impact as an instrument in
      psychotherapy or environmental therapy. For this reason a new cinematographic
      project applying widespread video technology in environmental therapy, too, has
      been launched. All patients at our psychiatric hospital are involved in film
      selection, can cooperate at different organizational levels, and have regular
      opportunities to see films. The technical, the organizational and, in particular,
      the legal preconditions are set out, followed by a report on experience gained in
      use of video films within the setting of a psychiatric hospital. Reference is
      also made to economic aspects, therapeutic effects and contraindications.

PMID- 10941774
TI  - [Discharge summary--business card of the psychiatric hospital?].
AB  - OBJECTIVE: Hospital discharge letters represent important means of communication
      between clinicians and physicians in private practice. They greatly contribute to
      continuous patient management. METHODS: A survey of the literature is carried out
      to provide a basis for an optimal psychiatric discharge letter. RESULTS:
      Deficiencies in quality of discharge summaries have been mentioned in many
      studies. These mainly concern delay and length of the letters. Well-structured
      form letters are preferred. Diagnosis, results of investigations, medication, and
      treatment after discharge are considered the most important details in the
      letter. CONCLUSIONS: Summarizing the results, the requirements for an optimal
      psychiatric discharge letter should be implemented in clinical practice to
      improve the record and also consumer satisfaction. Computer-generated discharge
      summaries can improve speed of delivery by using a standardized documentation
      system in psychiatry and new information technology.

PMID- 10941775
TI  - [Does modification of documentation result in a reduction of medication to
      involuntary patients?].
AB  - OBJECTIVE: The effects of modification of documentation on the administration of
      psychotropic medication to involuntary patients in hospital were investigated.
      METHODS: The charts of 414 inpatients on the acute-ward were reviewed two months
      before and two months after a new form for documentation of rationales for
      medication administration to involuntary patients was instituted. A follow-up was
      carried out for a two-month period a year later. RESULTS: The percentage of
      patients who received medication involuntarily, 70% of whom were schizophrenic,
      fell by over half, from 12% to 5%, after additional standardized documentation
      for the use of such medications was instituted. The number of medications
      administered to involuntary patients fell from 80 to 21, a reduction of 74%. The
      effects were stable over the course of one year. CONCLUSIONS: Modification of
      documentation seems to reduce the use of medication with involuntary patients.

PMID- 10941776
TI  - [Perspectives on medical research by relatives of patients with Creutzfeldt-Jakob
      disease].
AB  - OBJECTIVE: To assess the attitude of Creutzfeldt-Jakob patients relatives and of
      relatives of cognitively unimpaired individuals towards dementia research by a
      questionnaire survey. METHODS: 42 relatives of cases and 41 controls who were
      interviewed within the german part of the European Union collaborative study of
      CJD were asked to answer structured questions concerning their personal attitude
      towards three hypothetical projects: a diagnostic research project without
      personal benefit, a project with possible therapeutic option and a study of
      hereditary dementia. RESULTS: 31 relatives of cases and 26 relatives of the
      controls were willing to participate in this survey. In both groups the
      willingness to participate in dementia research is high. Research without
      approval of patients or relatives is rejected in most cases. Relatives want to
      decide to which extent genetic results are used for scientific or personal
      purposes. CONCLUSIONS: Although research with (and for) demented patients is
      restricted by the law in many countries to certain limits, relatives are willing
      to participate in these efforts to a greater extend than expected. As long as the
      responsible physicians will respect their demented patients as severely ill human
      beings, the view towards research is this field might be as positive as shown in
      this sample.

PMID- 10941777
TI  - [Agoraphobia with panic disorder or epilepsy? Differential diagnostic
      considerations in a case].
AB  - This paper describes a patient suffering from agoraphobia with panic disorder and
      with a history of self-induced epileptic seizures. The anxiety syndrome causing
      the admission to hospital could be diagnosed as non epileptic. He was treated
      successfully with a behaviour therapy. We discuss the possible interactions
      between anxiety disorders and epileptic seizures and some diagnostic
      demarcations. We conclude that even people with mild forms of epilepsy may
      develop an anxiety disorder arising from the fear of again getting epileptic
      seizures. To work out the different syndromes of epileptic seizures and of panic
      attacks should be part of the therapy.

PMID- 10941778
TI  - [Acute psychotic reaction related to the change of government in Austria].

PMID- 10941779
TI  - Quorum regulation of luminescence in Vibrio fischeri.
AB  - Luminescence in Vibrio fischeri is controlled by a population density-responsive
      regulatory mechanism called quorum sensing. Elements of the mechanism include:
      LuxI, an acyl-homoserine lactone (acyl-HSL) synthase that directs synthesis of
      the diffusible signal molecule, 3-oxo-hexanoyl-HSL (V. fischeri autoinducer-1,
      VAI-1); LuxR, a transcriptional activator protein necessary for response to VAI
      1; GroEL, which is necessary for production of active LuxR; and AinS, an acyl-HSL
      synthase that catalyzes the synthesis of octanoyl-HSL (VAI-2). The population
      density-dependent accumulation of VAI-1 triggers induction of lux operon
      (luxICDABEG; genes for luminescence enzymes and for LuxI) transcription and
      luminescence by binding to LuxR, forming a complex that facilitates the
      association of RNA polymerase with the luxoperon promoter. VAI-2, which
      apparently interferes with VAI-1 binding to LuxR, operates to limit premature
      luxoperon induction. Hierarchical control is imposed on the system by 3':5'
      cyclic AMP (cAMP) and cAMP receptor protein (CRP), which are necessary for
      activated expression of luxR. Several non-lux genes in V. fischeri are controlled
      by LuxR and VAI-1. Quorum regulation in V. fischeri serves as a model for
      LuxI/LuxR-type quorum sensing systems in other gram-negative bacteria.

PMID- 10941780
TI  - The Euprymna scolopes-Vibrio fischeri symbiosis: a biomedical model for the study
      of bacterial colonization of animal tissue.
AB  - The diversity of microorganisms found in the marine environment reflects the
      immense size, range of physical conditions and energy sources, and evolutionary
      age of the sea. Because associations with living animal tissue are an important
      and ancient part of the ecology of many microorganisms, it is not surprising that
      the study of marine symbioses (including both cooperative and pathogenic
      interactions) has produced numerous discoveries of biotechnological and
      biomedical significance. The association between the bioluminescent bacterium
      Vibrio fischeri and the sepiolid squid Euprymna scolopes has emerged as a
      productive model system for the investigation of the mechanisms by which
      cooperative bacteria initiate colonization of specific host tissues. The results
      of the last decade of research on this system have begun to reveal surprising
      similarities between this association and the pathogenic associations of disease
      causing Vibrio species, including those of interest to human health and
      aquaculture. Studies of the biochemical and molecular events underlying the
      development of the squid-vibrio symbiosis can be expected to continue to increase
      our understanding of the factors controlling both benign and pathogenic bacterial
      associations.

PMID- 10941781
TI  - Bacterial signals and antagonists: the interaction between bacteria and higher
      organisms.
AB  - It is now well established that bacteria communicate through the secretion and
      uptake of small diffusable molecules. These chemical cues, or signals, are often
      used by bacteria to coordinate phenotypic expression and this mechanism of
      regulation presumably provides them with a competitive advantage in their natural
      environment. Examples of coordinated behaviors of marine bacteria which are
      regulated by signals include swarming and exoprotease production, which are
      important for niche colonisation or nutrient acquisition (e.g. protease breakdown
      of substrate). While the current focus on bacterial signalling centers on N
      Acylated homoserine lactones, the quorum sensing signals of gram-negative
      bacteria, these are not the only types of signals used by bacteria. Indeed, there
      appears to be many other types of signals produced by bacteria and it also
      appears that a bacterium may use multiple classes of signals for phenotypic
      regulation. Recent work in the area of marine microbial ecology has led to the
      observation that some marine eukaryotes secrete their own signals which compete
      with the bacterial signals and thus inhibit the expression of bacterial
      signalling phenotypes. This type of molecular mimicry has been well characterised
      for the interaction of marine prokaryotes with the red alga, Delisea pulchra.

PMID- 10941782
TI  - Microbial symbionts of marine invertebrates: opportunities for microbial
      biotechnology.
AB  - Marine invertebrates are sources of a diverse array of bioactive metabolites with
      great potential for development as drugs and research tools. In many cases,
      microorganisms are known or suspected to be the biosynthetic source of marine
      invertebrate natural products. The application of molecular microbiology to the
      study of these relationships will contribute to basic biological knowledge and
      facilitate biotechnological development of these valuable resources. The
      bryostatin-producing bryozoan B. neritina and its specific symbiont "Candidatus
      Endobugula sertula" constitute one promising model system. Another fertile
      subject for investigation is the listhistid sponges that contain numerous
      bioactive metabolites, some of which originate from bacterial symbionts.

PMID- 10941783
TI  - Microbial gene transfer: an ecological perspective.
AB  - Microbial gene transfer or microbial sex is a means of exchanging loci amongst
      prokaryotes and certain eukaryotes. Historically viewed as a laboratory artifact,
      recent evidence from natural populations as well as genome research has indicated
      that this process may be a major driving force in microbial evolution. Studies
      with natural populations have taken two approaches- either adding a defined donor
      with a traceable gene to an indigenous community, and detecting the target gene
      in the indigenous bacteria, or by adding a model recipient to capture genes being
      transferred from the ambient microbial flora. However, both approaches usually
      require some cultivation of the recipient, which may result in a dramatic
      underestimation of the ambient transfer frequency. Novel methods are just
      evolving to study in situ gene transfer processes, including the use of green
      fluorescent protein (GFP)-marked plasmids, which enable detection of
      transferrants by epifluorescence microscopy. A transduction-like mechanism of
      transfer from viral-like particles produced by marine bacteria and thermal spring
      bacteria to Escherichia coil has been documented recently, indicating that broad
      host range transduction may be occurring in aquatic environments. The sequencing
      of complete microbial genomes has shown that they are a mosaic of ancestral
      chromosomal genes interspersed with recently transferred operons that encode
      peripheral functions. Archaeal genomes indicate that the genes for replication,
      transcription, and translation are all eukaryotic in complexity, while the genes
      for intermediary metabolism are purely bacterial. And in eukaryotes, many
      ancestral eukaryotic genes have been replaced by bacterial genes believed derived
      from food sources. Collectively these results indicate that microbial sex can
      result in the dispersal of loci in contemporary microbial populations as well as
      having shaped the phylogenies of microbes from multiple, very early gene transfer
      events.

PMID- 10941784
TI  - The multiple identities of Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is a ubiquitous marine bacterium and human pathogen. The
      organism possesses multiple cell types appropriate for life under different
      circumstances. The swimmer cell, with a single polar flagellum, is adapted to
      life in liquid environments. The polar flagellum is powered by the sodium motive
      force and can propel the bacterium at fast speeds. The swarmer cell, propelled by
      many proton-powered lateral flagella, can move through highly viscous
      environments, colonize surfaces, and form multicellular communities which
      sometimes display highly periodic architecture. Signals that induce
      differentiation to the surface-adapted cell type are both physical and chemical
      in nature. Surface-induced gene expression may aid survival, whether attached to
      inanimate surfaces or in a host organism. Genetic rearrangements create
      additional phenotypic versatility, which is manifested as variable opaque and
      translucent colony morphotypes. Discovery that a LuxR homolog controls the opaque
      cell type implicates intercellular signaling as an additional survival strategy.
      The alternating identities of V. parahaemolyticus may play important roles in
      attachment and detachment, how bacterial populations adapt to growth on surfaces,
      form structured communities, and develop biofilms.

PMID- 10941785
TI  - Non-flagellar swimming in marine Synechococcus.
AB  - Certain marine unicellular cyanobacteria of the genus Synechococcus exhibit a
      unique type of swimming motility characterized by the absence of flagella and of
      any other obvious organelle of motility. Although the mechanism responsible for
      this phenomenon remains mysterious, recent advances have included the development
      of testable models as well as the identification of a cell-surface polypeptide
      that is required for the generation of thrust. These developments, as well as the
      future research directions they suggest, are discussed.

PMID- 10941786
TI  - Petroleum biodegradation in marine environments.
AB  - Petroleum-based products are the major source of energy for industry and daily
      life. Petroleum is also the raw material for many chemical products such as
      plastics, paints, and cosmetics. The transport of petroleum across the world is
      frequent, and the amounts of petroleum stocks in developed countries are
      enormous. Consequently, the potential for oil spills is significant, and research
      on the fate of petroleum in a marine environment is important to evaluate the
      environmental threat of oil spills, and to develop biotechnology to cope with
      them. Crude oil is constituted from thousands of components which are separated
      into saturates, aromatics, resins and asphaltenes. Upon discharge into the sea,
      crude oil is subjected to weathering, the process caused by the combined effects
      of physical, chemical and biological modification. Saturates, especially those of
      smaller molecular weight, are readily biodegraded in marine environments.
      Aromatics with one, two or three aromatic rings are also efficiently biodegraded;
      however, those with four or more aromatic ring are quite resistant to
      biodegradation. The asphaltene and resin fractions contain higher molecular
      weight compounds whose chemical structures have not yet been resolved. The
      biodegradability of these compounds is not yet known. It is known that the
      concentrations of available nitrogen and phosphorus in seawater limit the growth
      and activities of hydrocarbon-degrading microorganisms in a marine environment.
      In other words, the addition of nitrogen and phosphorus fertilizers to an oil
      contaminated marine environment can stimulate the biodegradation of spilled oil.
      This notion was confirmed in the large-scale operation for bioremediation after
      the oil spill from the Exxon Valdez in Alaska. Many microorganisms capable of
      degrading petroleum components have been isolated. However, few of them seem to
      be important for petroleum biodegradation in natural environments. One group of
      bacteria belonging to the genus Alcanivorax does become predominant in an oil
      contaminated marine environment, especially when nitrogen and phosphorus
      fertilizers are added to stimulate the growth of endogenous microorganisms.

PMID- 10941787
TI  - Marine Bacillus spores as catalysts for oxidative precipitation and sorption of
      metals.
AB  - The oxidation of soluble manganese(II) to insoluble Mn(III,IV) oxide precipitates
      plays an important role in the environment. These Mn oxides are known to oxidize
      numerous organic and inorganic compounds, scavenge a variety of other metals on
      their highly charged surfaces, and serve as electron acceptors for anaerobic
      respiration. Although the oxidation of Mn(II) in most environments is believed to
      be bacterially-mediated, the underlying mechanisms of catalysis are not well
      understood. In recent years, however, the application of molecular biological
      approaches has provided new insights into these mechanisms. Genes involved in Mn
      oxidation were first identified in our model organism, the marine Bacillus sp.
      strain SG-1, and subsequently have been identified in two other phylogenetically
      distinct organisms, Leptothrix discophora and Pseudomonas putida. In all three
      cases, enzymes related to multicopper oxidases appear to be involved, suggesting
      that copper may play a universal role in Mn(II) oxidation. In addition to
      catalyzing an environmentally important process, organisms capable of Mn(II)
      oxidation are potential candidates for the removal, detoxification, and recovery
      of metals from the environment. The Mn(II)-oxidizing spores of the marine
      Bacillus sp. strain SG-1 show particular promise, due to their inherent
      physically tough nature and unique capacity to bind and oxidatively precipitate
      metals without having to sustain growth.

PMID- 10941788
TI  - Formation of magnetosomes in magnetotactic bacteria.
AB  - The ability of magnetotactic bacteria to orient and migrate along geomagnetic
      field lines is based on intracellular magnetic structures, the magnetosomes,
      which comprise nano-sized, membrane bound crystals of magnetic iron minerals. The
      formation of magnetosomes is achieved by a biological mechanism that controls the
      accumulation of iron and the biomineralization of magnetic crystals with a
      characteristic size and morphology within membrane vesicles. This paper focuses
      on the current knowledge about magnetotactic bacteria and will outline aspects of
      the physiology and molecular biology of magnetosome formation. The
      biotechnological potential of the biomineralization process is discussed.

PMID- 10941789
TI  - Pressure response in deep-sea piezophilic bacteria.
AB  - Several piezophilic bacteria have been isolated from deep-sea environments under
      high hydrostatic pressure. Taxonomic studies of the isolates showed that the
      piezophilic bacteria are not widely distributed in terms of taxonomic positions,
      and all were assigned to particular branches of the Proteobacteria gamma
      subgroup. A pressure-regulated operon from piezophilic bacteria of the genus
      Shewanella, S. benthica and S. violacea, was cloned and sequenced, and downstream
      of this operon another pressure regulated operon, cydD-C, was found. The cydD
      gene was found to be essential for the bacterial growth under high-pressure
      conditions, and the product of this gene was found to play a role in their
      respiratory system. Results obtained later indicated that the respiratory system
      in piezophilic bacteria may be important for survival in a high-pressure
      environment, and more studies focusing on other components of the respiratory
      chain have been conducted. These studies suggested that piezophilic bacteria are
      capable of changing their respiratory system in response to pressure conditions,
      and a proposed respiratory chain model has been suggested in this regard.

PMID- 10941790
TI  - Microbial adaptations to the psychrosphere/piezosphere.
AB  - Low temperature and high pressure deep-sea environments occupy the largest
      fraction of the biosphere. Nevertheless, the molecular adaptations that enable
      life to exist under these conditions remain poorly understood. This article will
      provide an overview of the current picture on high pressure adaptation in cold
      oceanic environments, with an emphasis on genetic experiments performed on
      Photobacterium profundum. Thus far genes which have been found or implicated as
      important for pressure-sensing or pressure-adaptation include genes required for
      fatty acid unsaturation, the membrane protein genes toxR and rseC and the DNA
      recombination gene recD. Many deep-sea bacteria possess genes for the production
      of omega-3 polyunsaturated fatty acids. These could be of biotechnological
      significance since these fatty acids reduce the risk of cardiovascular disease
      and certain cancers and are useful as dietary supplements.

PMID- 10941791
TI  - Adaptation of proteins from hyperthermophiles to high pressure and high
      temperature.
AB  - Further clarification of the adaptations permitting the persistence of life at
      temperatures above 100 degrees C depends in part on the analysis of adaptive
      mechanisms at the protein level. The hyperthermophiles include both Bacteria and
      Archaea, although the majority of isolates growing at or above 100 degrees C are
      Archaea. Newly described adaptive features of hyperthermophiles include proteins
      whose structural integrity persists at temperatures up to 200 degrees C, and
      under elevated hydrostatic pressure, which in some cases adds significant
      increments of stability.

PMID- 10941793
TI  - The Purloined Letter: bacterial orthologs of archaeal NMN adenylyltransferase are
      domains within multifunctional transcription regulator NadR.

PMID- 10941792
TI  - The RND permease superfamily: an ancient, ubiquitous and diverse family that
      includes human disease and development proteins.
AB  - A previous report identified and classified a small family of gram-negative
      bacterial drug and heavy metal efflux permeases, now commonly referred to as the
      RND family (TC no. 2.6). We here show that this family is actually a ubiquitous
      superfamily with representation in all major kingdoms. We report phylogenetic
      analyses that define seven families within the RND superfamily as follows: (1)
      the heavy metal efflux (HME) family (gram negative bacteria), (2) the
      hydrophobe/amphiphile efflux-1 (HAE1) family (gram negative bacteria), (3) the
      nodulation factor exporter (NFE) family (gram negative bacteria), (4) the SecDF
      protein-secretion accessory protein (SecDF) family (gram negative and gram
      positive bacteria as well as archaea), (5) the hydrophobe/amphiphile efflux-2
      (HAE2) family (gram positive bacteria), (6) the eukaryotic sterol homeostasis
      (ESH) family, and (7) the hydrophobe/amphiphile efflux-3 (HAE3) family (archaea
      and spirochetes). Functionally uncharacterized proteins were identified that are
      members of the RND superfamily but fall outside of these seven families. Some of
      the eukaryotic homologues function as enzymes and receptors instead of (or in
      addition to) transporters. The sizes and topological patterns exhibited by
      members of all seven families are shown to be strikingly similar, and statistical
      analyses establish common descent. Multiple alignments of proteins within each
      family allow derivation of family-specific signature sequences. Structural,
      functional, mechanistic and evolutionary implication of the reported results are
      discussed.

PMID- 10941794
TI  - High level production of thermostable alpha-amylase from Sulfolobus solfataricus
      in high-cell density culture of the food yeast Candida utilis.
AB  - The alpha-amylase from Sulfolobus solfataricus has the commercially important
      ability to hydrolyze glycosyltrehalose and can be used for the production of
      trehalose from soluble starch. We have produced this enzyme in the food yeast
      Candida utilis at extremely high levels. Because the S. solfataricus gene was
      previously shown to be very poorly expressed, the gene was resynthesized based on
      codons preferentially found in the highly expressed C. utilis glyceraldehyde-3
      phosphate dehydrogenase (GAP) gene. Expression of this synthetic gene under the
      control of the GAP promoter yielded biologically active alpha-amylase, accounting
      for more than 50% of the soluble protein. Comparison of the expression levels of
      various chimeric constructs of the synthetic and native genes indicated that the
      production level of the alpha-amylase was improved more than 2x10(4)-fold by
      substituting the native gene with the synthesized one. Northern analysis revealed
      the formation of short mRNAs in transformants with constructs containing native
      gene fragments, suggesting that premature termination of the transcripts is
      responsible for the low production level. The alpha-amylase-producing C. utilis
      cells were grown up to 92 grams dry cell weight per liter in a synthetic medium,
      yielding 12.3 g/l alpha-amylase which accounts for up to 27% of total cell
      proteins.

PMID- 10941795
TI  - Automation of yeast two-hybrid screening.
AB  - We have developed an automated format for screening yeast two-hybrid libraries
      for protein-protein interactions. The format consists of a liquid array in which
      pooled library subsets of yeast, expressing up to 1000 different cDNAs, are mated
      to a yeast strain of the opposite mating type, expressing a protein of interest.
      Interactors are detected by a liquid assay for beta-galacsidase following
      prototrophic selection. The method is demonstrated by the detection of
      interactions between two encoded yeast RNA polymerase subunits in simulated
      libraries of varied complexity. To demonstrate its utility for large scale
      screening of complex cDNA libraries, two nuclear receptor ligand-binding domains
      were screened through two cDNA libraries arrayed in pooled subsets. Screening
      these libraries yielded clones which had previously been identified in
      traditional yeast two hybrid screens, as well as several new putative interacting
      proteins. The formatting of the cDNA library into pooled subsets lends itself to
      functional subtraction of the promiscuous positive class of interactor from the
      library. Also, the liquid arrayed format enables electronic handling of the data
      derived from interaction screening, which, together with the automated handling
      of samples, should promote large-scale proteome analysis.

PMID- 10941796
TI  - The catabolite control protein CcpA controls ammonium assimilation in Bacillus
      subtilis.
AB  - Carbon catabolite repression of several catabolic operons in Bacillus subtilis is
      mediated by the repressor CcpA. An inactivation of the ccpA gene has two distinct
      phenotypes: (i) catabolite repression of catabolic operons is lost and (ii) the
      growth of bacteria on minimal medium is severely impaired. We have analyzed the
      physiological properties of a ccpA mutant strain and show that the ccpA mutation
      does not affect sugar transport. We have isolated extragenic suppressors of ccpA
      that suppress the growth defect (sgd mutants). Catabolite repression of beta
      xylosidase synthesis was, however, not restored suggesting that the suppressor
      mutations allow differentiation between the phenotypes of the ccpA mutant. A
      close inspection of the growth requirements of the ccpA mutant revealed the
      inability of the mutant to utilize inorganic ammonium as a single source of
      nitrogen. An intact ccpA gene was found to be required for expression of the
      gltAB operon encoding glutamate synthase. This enzyme is necessary for the
      assimilation of ammonium. In a sgd mutant, gltAB operon expression was no longer
      dependent on ccpA, suggesting that the poor expression of the gltAB operon is
      involved in the growth defect of the ccpA mutant.

PMID- 10941797
TI  - RecA interacts with Klenow and enhances fidelity of DNA synthesis in vitro.
AB  - To understand the molecular basis of RecA-mediated DNA-repair, we tested the
      replicative fidelity of the large fragment of Pol I (Klenow) in RecA-DNA
      complexes in vitro. Klenow synthesis was error-prone in naked DNA substrates but
      essentially error-free in RecA coated complexes. Escherichia coli SSB, causes no
      such improvement in Klenow fidelity. RecA filaments promote better exonucleolytic
      proofreading by Klenow than on naked DNA substrates at select sites when
      replication is "stalled" due to a missing dNTP. Addition of RecA to pyrene
      sulfonylchloride-labeled Klenow resulted in a specific increase in steady-state
      fluorescence anisotropy and a concomitant decrease in fluorescence lifetime.
      These observations suggest the possibility of a direct interaction between RecA
      and Klenow even in the absence of DNA which may mediate the observed improvement
      in Klenow fidelity.

PMID- 10941798
TI  - Anaerobic degradation of ethylbenzene and toluene in denitrifying strain EbN1
      proceeds via independent substrate-induced pathways.
AB  - Denitrifying strain EbN1 utilizes either ethylbenzene or toluene as the sole
      source of organic carbon under strictly anoxic conditions. When cells were grown
      on ethylbenzene, 1-phenylethanol and acetophenone were detected in the culture
      supernatant. However, these two compounds were not observed when cells were grown
      on benzoate. Growth on ethylbenzene, 1-phenylethanol, or acetophenone strictly
      depended on the presence of CO2, whereas growth on benzoate did not. These
      results suggest that strain EbN1 degrades ethylbenzene via 1-phenylethanol and
      acetophenone as intermediates, and that acetophenone is subsequently
      carboxylated. In suspensions of benzoate-grown cells, induction was required for
      degradation of ethylbenzene, 1-phenylethanol, and acetophenone. Induction was
      also required for toluene-grown cells to gain activity to degrade ethylbenzene,
      and, conversely, for ethylbenzene-grown cells to degrade toluene. In accordance
      with our findings from these studies, two-dimensional gel electrophoretic
      analysis of extracts of cells grown on benzoate, acetophenone, ethylbenzene, or
      toluene showed that a number of substrate-specific proteins were induced in
      strain EbN1. Growth on toluene or ethylbenzene induced a distinct set of
      proteins. However, some of the induced proteins in ethylbenzene or acetophenone
      grown cells were identical. This agrees with the finding that acetophenone is an
      intermediate in the degradation of ethylbenzene.

PMID- 10941799
TI  - Ribose utilization in Lactobacillus sakei: analysis of the regulation of the rbs
      operon and putative involvement of a new transporter.
AB  - A 7-kb DNA fragment of Lactobacillus sakei, containing the rbsD, rbsK and rbsR
      genes was sequenced. The genes responsible for ribose utilization are organized
      differently from what was previously described for model organisms such as
      Escherichia coli and Bacillus subtilis. No gene encoding RbsA, RbsB and RbsC, the
      subunits of the ribose ABC-transporter, were present in the rbs gene cluster.
      Instead, we found an open reading frame coding for RbsU, a protein similar to
      GltA, the glucose transporter of Staphylococcus xylosus. The disruption of rbsK,
      encoding the ribokinase, impaired growth on ribose. The disruption of rbsR,
      encoding the repressor, had no effect on the ability to grow on ribose, but led
      to overexpression of a large transcript corresponding to rbsU, rbsD and rbsK,
      suggesting that RbsU might be involved in ribose utilization. Ribose uptake and
      phosphorylation assays on the wild type strain and various mutants showed that,
      in ptsI mutants, both ribose uptake and phosphorylation are increased. These
      increased activities can explain the faster growth rate on ribose that was
      observed in ptsI mutants. The phosphotransferase system is thus involved in the
      negative regulation of ribose utilization. This regulation might not act at the
      transcriptional level since the overexpression of the rbs genes in the rbsR
      mutant did not lead to the same phenotype. A gene sharing high similarity scores
      with ackA genes, encoding the acetate kinase, was found upstream from the rbs
      gene cluster. The unusual location of this gene is maybe not fortuitous since
      acetate kinase is involved in ribose catabolism.

PMID- 10941800
TI  - Sequence motifs determine structure and Ca++-binding by EF-hand proteins.
AB  - Prediction of protein structural and functional characteristics based on specific
      motif interactions could serve as a powerful tool in many facets of the
      biological sciences. Such improvements in protein modeling will be instrumental
      in the enhancement of drug design. A new approach to a sequence description of EF
      hand motifs with more than one EF-hand domain is presented here; this permits
      precise insight into the structural and functional properties of many members of
      the EF-hand superfamily of calcium-binding proteins. Three separate regular
      expressions, or signatures, are used to describe an EF-hand motif, and specific
      relationships must exist between the two sequence motifs for the two neighboring
      EF-hands in a given calcium-binding domain. Specifically, each of the sequence
      motifs has a conserved phenylalanine. These two phenylalanine residues are
      separated by 57+/-10 amino acid residues but interact closely with each other in
      the tertiary structure of the calcium-binding domain. Changes in conserved
      residues in the sequence motifs have been shown experimentally to decrease or
      eliminate the ability of the protein to bind calcium. This new approach of use of
      multiple sequence motifs, with motif interrelationships, yields a highly specific
      and robust tool for the prediction of structural and functional properties of new
      and novel proteins.

PMID- 10941801
TI  - Expression and characterization of E. coli-produced soluble, functional human
      dihydroorotate dehydrogenase: a potential target for immunosuppression.
AB  - Human dihydroorotate dehydrogenase (huDHODH) is essential for de novo
      biosynthesis of pyrimidines and the target of two immunosuppressive drugs,
      brequinar and the leflunomide metabolite A77-1726 (Chen et al., 1992; Davis et
      al., 1996). Using a T7 RNA polymerase expression system, we produced huDHODH as a
      fusion protein containing an amino-terminal decahistidine tag. Escherichia coli
      growth and expression conditions were optimized to enhance huDHODH solubility and
      to permit purification of the enzyme in the absence of detergent. Soluble
      huDHODH, purified by a simple two-step procedure, was catalytically active,
      monomeric, and contained a flavin mononucleotide (FMN) cofactor in a 1:1
      FMN/protein molar ratio. Kinetic analysis showed that huDHODH uses a two site
      ping-pong mechanism, where DHO is oxidized at one site and the second substrate,
      ubiquinone, is reduced at the other. This result is consistent with the mechanism
      proposed for bovine liver DHODH (Hines and Johnston, 1989).

PMID- 10941803
TI  - The predictive value of attributes of pain to classify rheumatoid arthritis.
AB  - Out of 2300 patients with rheumatic diseases 1627 were analysed to develop a
      classification of rheumatoid arthritis based on clinical attributes of pain. Of
      these, 641 patients had the disease and 986 were controls with other rheumatic
      conditions. For traditional format classification, six of eight variables were
      selected: pain at a fixed joint; symmetrical pain; continuous pain; pain mainly
      present at night or in the morning; pain following joint pressure; and pain
      decreased by load/movement. The occurrence of four or more of these features was
      associated with a 72.1% sensitivity and a 79.1% specificity. A classification
      tree constructed on four features that showed the greatest diagnostic power
      (symmetrical pain, pain mainly present at night or in the morning, pain at joint
      pressure, continuous pain), was associated with a 75.8% sensitivity and a 77.0%
      specificity.

PMID- 10941802
TI  - Patients with fibromyalgia benefit from aerobic endurance exercise.
AB  - Fibromyalgia (FM) is a disorder characterised by diffuse widespread
      musculoskeletal aching and stiffness and multiple tender points [1]. Its
      pathophysiology is poorly understood. The influence of aerobic endurance exercise
      on pain in patients with FM was investigated. Twenty-seven patients (25 female, 2
      male) participated in a controlled clinical study and performed 12 weeks of
      jogging, walking, cycling or swimming following a given schedule. Twelve
      sedentary FM patients (11 female, 1 male) served as controls. Before and after
      training both the study and the control groups were evaluated
      spiroergometrically. Tender point pain was quantified by dolorimetry. The painful
      body surface was estimated by a pain body diagram, and its intensity by a visual
      analogue scale and a ranking scale. Patients trained for an average of 25 min two
      to three times a week, with an average intensity of 50% of maximal oxygen uptake
      (VO2max). Unlike the control group, the training group exhibited a decrease in
      heart rate and VO2 and an increase in respiratory quotient during submaximal
      workload. Maximal performance capacity and VO2max remained unchanged, whereas the
      wattpulse (watt/heart rate) improved at maximal workload. Pain parameters
      remained unchanged in the control group, but in the training group the mean
      number of positive tender points (15.4/12.7), the mean pain threshold of the
      gluteal tender point (2.89 kp/3.50 kp) and the painful body surface (18%/15% body
      surface) decreased significantly. Subjective general pain condition deteriorated
      in two patients but improved in 17. Our results suggest a positive effect of
      aerobic endurance exercise on fitness and well-being in patients with FM.

PMID- 10941804
TI  - A first molecular approach towards CGG repeat expansion in FMR1 gene in systemic
      lupus erythematosus and in Sjogren's syndrome: a preliminary report.
AB  - Co-occurrent autoimmune disease and fragile X syndrome has been reported in the
      literature and we have therefore studied the expansion of Cytosine-Guanine
      Guanine (CGG) repeat in FMR1 gene in a series of females with autoimmune diseases
      such as systemic lupus erythematosus and Sjogren's syndrome, with PCR and
      Southern blot methods. The average length of trinucleotide repeat was not
      increased in these female patients as compared with controls. These preliminary
      data on a short series of patients suggest a possible absence of trinucleotide
      repeat expansion abnormality associated with autoimmune diseases such as systemic
      lupus erythematosus and Sjogren's syndrome.

PMID- 10941805
TI  - CLINHAQ scale--validation of a Hebrew version in patients with fibromyalgia.
      Clinical Health Assessment Questionnaire.
AB  - Assessment of health status in patients with rheumatic disease, including
      fibromyalgia (FM), using structured questionnaires has become an important
      approach to evaluate treatment and outcome. The objectives of this study were to
      validate a translated version of the Clinical Health Assessment Questionnaire
      (CLINHAQ) to be used by Hebrew-speaking populations, and specifically to evaluate
      its usefulness in fibromyalgia syndrome (FM). The CLINHAQ was translated into
      Hebrew and administered to 90 women with FM along with the Hebrew versions of the
      Fibromyalgia Impact Questionnaire (FIQ) and the Quality of Life (QOL) Scale. The
      CLINHAQ includes scales of functional disability, helplessness, anxiety and
      depression, as well as assessment of current health status and satisfaction with
      this. All subjects were asked about the presence and severity (assessed by visual
      analogue scale) of current FM symptoms (pain, fatigue, anxiety etc.); a count of
      18 tender points was conducted by thumb palpation, and tenderness thresholds were
      measured by dolorimetry. Test-retest reliability was assessed by Pearson
      correlation coefficients, and internal consistency was evaluated with Cronbach's
      alpha coefficient of reliability. Construct validity was tested by correlating
      the CLINHAQ items with measures of symptom severity, count of tender point,
      tenderness thresholds, physical functioning measured by FIQ, and with a score of
      QOL. Test-retest reliability coefficients ranged from 0.82 to 0.99, and
      Cronbach's alpha coefficients from 0.725 to 0.929. Significant moderate to high
      correlations were obtained between most subscales of CLINHAQ and measures of
      physical functioning, quality of life and severity of FM symptoms. In conclusion,
      the CLINHAQ is a reliable and valid instrument for measuring health status and
      physical functioning in Israeli women with FM.

PMID- 10941806
TI  - Changes of CD4/CD8 ratio and interleukin-16 in systemic lupus erythematosus.
AB  - The authors investigated changes in the ratio of CD4+ to CD8+ T cells (CD4/CD8
      ratio) and T-cell activation, indicated by human leukocyte antigen (HLA)-DR
      expression, in patients with systemic lupus erythematosus (SLE) following
      treatment. An increase was observed in the CD4/CD8 ratio as well as a decrease in
      the expression of HLA-DR on T cells with the improvement of clinical
      manifestations on treatment with steroids or cyclosporine (CSA). In addition,
      steroid treatment suppressed whereas CSA treatment exerted no perceptible
      influence on the serum interleukin (IL)-16 level, concurrent with changes in T
      cell phenotypes. This indicated that the mechanism of the change in the CD4/CD8
      ratio differed depending on the drug, and CD8+ T cells could play an important
      role in reducing this ratio. The CD4/CD8 ratio and HLA-DR expression may be good
      indicators of therapeutic efficacy in some SLE patients.

PMID- 10941807
TI  - Oxidant/antioxidant status of the erythrocytes from patients with rheumatoid
      arthritis.
AB  - It has been suggested that enzymatic and/or non-enzymatic antioxidant systems are
      impaired in rheumatoid arthritis (RA) and hence patients are exposed to oxidant
      stress. This study aimed to establish whether this is really the case. Fasting
      blood samples were obtained from 24 patients with rheumatoid arthritis and 20
      controls. The activities of erythrocyte superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) enzymes and
      malondialdehyde (MDA), oxidant resistant (OR) and non-enzymatic superoxide
      radical scavenger activity (NSSA) values were measured in both groups. Patients
      with RA had higher SOD and XO activities and MDA levels than did the controls.
      However, NSSA and OR levels were found to be decreased, and CAT and GSH-Px
      activities unchanged in the study group. Results suggest that excessive free
      radical production through the xanthine-xanthine oxidase system is the primary
      factor in rheumatoid arthritis, rather than an impaired antioxidant system. The
      therapeutic use of XO enzyme inhibitors and some antioxidants can be beneficial
      in this regard.

PMID- 10941808
TI  - Utilisation and costs of investigations, and accuracy of diagnosis of polymyalgia
      rheumatica by family physicians.
AB  - To determine the utilisation and costs of investigations, and the accuracy of
      polymyalgia rheumatica (PMR) by family physicians, a retrospective chart review
      of 123 patients referred to a tertiary care rheumatology clinic was undertaken.
      The accuracy of diagnosis of PMR in the cohort was 24%. A variable number of
      investigations and costs occurred prior to referral, ranging from $110 in those
      with an unspecified locomotor diagnosis, through $74 in those with a correct
      diagnosis of PMR, to $24 where no diagnosis was entertained. In general, these
      costs were considered higher than necessary to make the diagnosis compared to
      those advocated by rheumatologists. We conclude that there is a low accuracy of
      diagnosis of PMR and an overutilisation of investigations, with resultant
      increased costs, by family physicians referring patients with PMR. Appropriate
      educational interventions are required to address both diagnostic and
      investigational needs.

PMID- 10941809
TI  - High incidence of parvovirus B19 DNA in synovial tissue of patients with
      undifferentiated mono- and oligoarthritis.
AB  - A common problem in rheumatological practice is inflammatory joint disease that
      cannot be classified. The prognosis of such undifferentiated arthritides is
      uncertain. The synovial tissue of 41 consecutive patients with various forms of
      arthritis was tested for the presence of viral DNA in a diagnosis-unaware
      fashion, using the polymerase chain reaction (PCR). Of all tested viruses,
      cytomegalovirus and parvovirus B19 were positive (each in 10 patients, two double
      positives), whereas herpes simplex virus was positive in two patients. Rubella
      virus RNA was detected in three specimens. When the positivity for viral material
      was analysed in terms of distribution among the various diagnostic groups, it
      became evident that five out of 10 parvovirus B 19-positive patients belonged to
      the undifferentiated arthritis group, whereas cytomegalovirus-positive patients
      were spread among all diagnostic groups. This indicates the possibility of a new
      diagnostic category of undifferentiated mono- and oligoarthritis, which can be
      identified by the presence of parvovirus B19 DNA in synovial tissue.

PMID- 10941810
TI  - A 'made in one piece' skeleton in a 22-year-old man suffering from sickle cell
      anaemia.
AB  - A 22-year-old African male with known sickle cell anaemia was referred by a
      Congolese medical centre with a request to improve his poor physical condition.
      He was unable to walk, stand or sit because his large joints and his spine were
      either ankylosed or very rigid. Radiographs showed joint fusion from the third to
      the fifth cervical vertebrae, of both hips, of the left knee, and a bilateral
      osteonecrosis of the humeral head. There was no scintigraphic evidence for an
      active osteomyelitis (99mTc-MDP (methyldiphosphonate) bone scan, Tc monoclonal
      antigranulocyte scan and 99mTc sulphur colloid scan). To improve his mobility the
      right femoral head was resected in June 1997; 14 days later the left femoral head
      was resected. Four months after the resection of the right hip, a right
      uncemented total hip prosthesis was implanted on this side. One month later the
      same type of hip arthroplasty was performed on the left side. During the
      postoperative rehabilitation period the patient regained autonomy. We have found
      no previous reports of such severe and multiple joint complications in a single
      patient suffering from sickle cell anaemia.

PMID- 10941811
TI  - Sensitivity of the HEp-2000 substrate for the detection of anti-SSA/Ro60
      antibodies.
AB  - Anti-SSA/Ro antibodies are the most prevalent type of antinuclear antibody (ANA).
      Anti-SSA/ Ro-positive sera may recognise two proteins: a 52 kDa (Ro52) and a 60
      kDa (Ro60) subunit. We studied the sensitivity for Ro60 detection using the HEp
      2000 substrate, which consists of HEp-2 cells transfected with Ro60 cDNA in an
      anti-SSA/Ro-positive population consecutively identified by double
      immunodiffusion (DID) with thymus/spleen nuclear extract and line immunoassay
      (LIA) with recombinant Ro52 and Ro60. One hundred and twenty-seven consecutive
      anti-SSA/Ro-positive sera defined by DID with thymus/spleen nuclear extract and
      LIA using recombinant Ro52 and Ro60 were analysed on HEp-2000 and DID with
      natural Ro60. Of these, 91 were anti-Ro60 positive on LIA and/ or DID with
      natural Ro60. The HEp-2000 substrate detected 70/91 (sensitivity 77%) and
      correlated strongest with DID. Most of the missed anti-Ro60-positive sera had
      high ANA intensity. The substrate did not detect monospecific anti-Ro52
      antibodies (sensitivity 9.7%; 3/31). HEp-2000 substrate can therefore be
      considered a reliable, simple and alternative method for DID in the detection of
      anti-Ro60 reactivity. Special follow-up should be given to sera with strong ANA
      patterns in which the SSA/Ro60 staining pattern may be hidden.

PMID- 10941812
TI  - Serum creatine kinase in patients with rheumatic diseases.
AB  - Serum creatine kinase (CK) activity is reduced in some conditions, including
      rheumatic diseases, but the aetiology and significance remain to be clarified.
      The aim of this study was to investigate relationships between serum CK activity
      and other muscle enzymes, muscle mass, renal function, steroid use and disease
      activity in patients with rheumatic diseases. Serum CK activity was measured in
      sera from 498 patients with rheumatic diseases: rheumatoid arthritis (RA, n =
      145), systemic lupus erythematosus (SLE, n = 31), spondyloarthropathies (SpA, n =
      35), polyarthralgia/arthritis (Poly, n = 74), miscellaneous group (MI, n = 46),
      and in non-inflammatory arthropathies (NIA, n = 167) as controls. Serum CK level
      was significantly reduced in RA (45.4 +/- 1.9 IU/l), SLE (46.4 +/- 4.2 IU/l), SpA
      (64.7 +/- 5.6 IU/l) and MI (63.4 +/- 4.8 IU/l), but not in poly (70.2 +/- 3.1
      IU/l), compared to controls (78.9 +/- 2.4 IU/l) (P < 0.05). CK values correlated
      with aspartate aminotransferase (AST), erythrocyte sedimentation rate (ESR), body
      mass index (BMI) and platelets (Plat) in RA; ESR and haemoglobin (Hb) in SLE,
      AST, ESR and Hb in SpA; lactate dehydrogenase (LDH), AST, ESR and Hb in Poly;
      LDH, AST, ESR, Hb and Ccr in MI; and LDH, AST and ESR in controls. In all
      patients with rheumatic diseases CK level was significantly correlated with LDH,
      AST, alanine aminotransferase (ALT), ESR, C-reactive protein (CRP) and BMI and
      prednisolone dose, but not with Ccr, age and disease duration. In conclusion, our
      data support the possibility that reduced CK activity is inversely correlated
      with inflammatory activity and correlated with other muscle enzymes, muscle mass
      and steroid use, but not with renal function, age and disease duration in
      rheumatic diseases.

PMID- 10941813
TI  - Psoriatic arthritis: interrelationships between skin and joint manifestations
      related to onset, course and distribution.
AB  - To assess the relationships between skin and joint disease, 70 patients with
      psoriatic arthritis were consecutively evaluated. Data were obtained regarding
      age, sex, duration of disease, age at onset, and flares of both skin and joint
      disease. Rheumatological assessment included morning stiffness, number of
      swollen, tender and deformed joints, involvement of distal interphalangeal joints
      (DIP), presence of dactylitis, Achilles tendinitis, and clinical lumbar and
      cervical involvement. Skin assessment included recording of the distribution of
      skin lesions and nail involvement, and grading of psoriasis severity using the
      PASI. The scalp was the most frequently involved site. Significant correlation
      was found between the PASI score and the number of deformed joints and Schober's
      test. The scalp score was found to correlate with the number of swollen joints,
      deformed joints, sausage finger and DIP involvement. Synchronous flares of skin
      and joint were significantly more frequent in the patients with onset of skin and
      joint diseases within the same year. Likewise, these patients showed a highly
      significant association between the PASI score and the number of tender, swollen
      and deformed joints, Schober's test and cervical involvement, whereas no such
      associations were found among patients with separate onset of skin and joint
      diseases.

PMID- 10941814
TI  - Evaluation of cerebrospinal fluid for the presense of anticardiolipin antibodies
      (aCL) in NP-SLE patients.
AB  - Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to
      the presence of anticardiolipin antibodies (aCL) in the patient's sera. The aim
      of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in
      SLE patients with NP features. Fifteen SLE patients were studied, all with NP
      features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and
      blood-brain barrier impairment. Sera and CSF were tested by ELISA for the
      presence of aCL-IgG and aCL-IgM with and without beta2 glycoprotein (beta2 GPI)
      cofactor. CSF and sera of 50 low back pain patients served as controls. Six
      patients were aCL(+) and nine aCL(-). In all patients the general CSF examination
      was normal. In all patients the value of indices of intrathecal IgG synthesis
      were normal but oligoclonal protein was present in the CSF of three patients. In
      none of the patients was the blood-brain barrier impaired. Neither aCL-IgG nor
      aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in
      patients without cofactor beta2 GPI and with cofactor were as follows: for IgG
      class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative).
      We could not detect aCL in the CSF of patients with NP-SLE, even if sera were
      positive for aCL.

PMID- 10941815
TI  - Disseminated zygomycosis simulating cerebrovascular disease and pulmonary
      alveolar haemorrhage in a patient with systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) may be complicated with serious
      cerebrovascular accidents and pulmonary alveolar haemorrhage. The authors report
      an autopsy-proven angioinvasive zygomycosis in a patient with SLE. The clinical
      features of systemic zygomycosis in this patient masqueraded as SLE-related
      stroke and pulmonary haemorrhage. The case demonstrates that the simultaneous
      occurrence of complications that clinically suggest pulmonary haemorrhage and
      multiple brain infarcts in SLE patients should include the rare disseminated
      zygomycosis in the differential diagnosis.

PMID- 10941816
TI  - Endoscopic management of severe subglottic stenosis in Wegener's granulomatosis.
AB  - The optimal treatment for severe subglottic stenosis secondary to Wegener's
      granulomatosis remains controversial. We report the case of a symptomatic middle
      aged woman who was successfully treated with intratracheal dilation and
      intralesional injection of corticosteroids. The literature related to this issue
      is being reviewed.

PMID- 10941817
TI  - A case of Churg-Strauss syndrome presenting with cortical blindness.
AB  - A 46-year-old woman with a sudden sight loss due to infarction of the occipital
      lobes is reported. The association of pulmonary disease, digital ischaemia,
      polyneuropathy and peripheral eosinophilia led to a diagnosis of Churg-Strauss
      syndrome. Her vision partially improved by a treatment with steroids and monthly
      i.v. cyclophosphamide. To our knowledge, this is the first case of CSS with a
      sudden loss of vision due to bilateral occipital infarction.

PMID- 10941818
TI  - Dysphagia with multiple autoimmune disease.
AB  - Myasthenia gravis (MG) and polymyositis (PM) are organ-specific autoimmune
      diseases. Occasional reports describe patients with clinical and pathologic
      features of both. Achalasia is idiopathic in nature, but autoimmune and
      inflammatory mechanisms have been proposed for this disorder as well. We describe
      a patient with dysphagia who was diagnosed at different points in time with all
      these three rare conditions. Despite at least putatively having immune mechanisms
      in common, an association between the three has not been previously described.

PMID- 10941819
TI  - Lipoprotein(a) and lipids in relation to inflammation in rheumatoid arthritis.
AB  - The aim of this study is to evaluate whether lipoprotein(a) (Lp(a)) acts as the
      acute phase reactant and whether changes of lipids are related to inflammation in
      rheumatoid arthritis (RA). Lp(a) and lipids were measured after an overnight
      fast, before and after 14 days use of antiinflammatory agents and correlated with
      laboratory findings in 21 untreated RA patients and 19 healthy controls. Nine
      (42.3%) of 21 RA patients and 6 (31.6%) of 19 controls had high Lp(a) levels (>
      30 mg/dl) and the Lp(a) level was higher in RA patients compared with controls
      (27.1 +/- 5.3 vs 19.0 +/- 4.2 mg/dl) without significant difference (p > 0.05).
      There was no significant correlation between ESR and Lp(a) and lipids in RA
      patients except for HDL cholesterol (r = -0.563, p = 0.008). After
      antiinflammatory agent use for 14 days, change in ESR (ESRsample1-ESRsample2) was
      significantly and negatively correlated to changes in total and HDL cholesterols
      in RA patients. In conclusion, although Lp(a) tended to be higher in RA, we could
      not find a distinct acute phase pattern of Lp(a). But changes in total and HDL
      cholesterols were negatively correlated with inflammation in RA. Our data support
      the phenomenon that dyslipoproteinemia observed in RA is associated with
      inflammation.

PMID- 10941820
TI  - JCA in adult life: a study of long-term outcome in patients with JCA or adult RA.

PMID- 10941821
TI  - Serum neopterin levels in Behcet's syndrome.

PMID- 10941823
TI  - Molecular events of bacterial-induced maturation of dendritic cells.
AB  - In order to protect the body from infectious microorganisms, mammals have
      developed powerful lines of defense, consisting in innate and adaptive immune
      responses. The innate response is phylogenetically more ancient and, for a long
      time, it has been considered to be broadly directed to microorganisms. However,
      the discovery of a new class of receptors, involved in recognition of patterns
      characteristic of groups of microorganisms (the toll-like receptor family) has re
      evaluated the role of the innate immune system as a discriminating system.
      Indeed, there is increasing evidence that the induction of different types of
      effector adaptive responses are directed by the innate immune system after
      recognition of particular groups of pathogens. The central role of Dendritic
      cells (DC) in the induction of adaptive immune responses towards infectious
      agents has been extensively described, but, recently, a new role of DC as a link
      between the non-antigen- and the antigen-specific responses has been proposed. DC
      have, indeed, the capacity to recruit and activate cells of the innate immune
      system upon inflammation. Thus. understanding the interaction of bacteria with
      DC, and the early molecular events resulting from this interaction may shed some
      light on the mechanisms of initiation of the immune response to infectious agents
      and on aspects of invasiveness, pathogenicity, and the persistence of certain
      bacteria.

PMID- 10941822
TI  - Chemokines and dendritic cell traffic.
AB  - Localization in tissues and migration to lymphoid organs are essential steps in
      the immunobiology of dendritic cells (DC). Chemokines play an important role in
      guiding the traffic of DC. Receptor expression and responsiveness to
      constitutively made chemokines account for the presence of DC in normal tissues.
      Inflammatory chemokines and nonchemokine attractants promote recruitment and
      localization of DC at sites of inflammation and infection. Upon exposure to
      maturation signals, DC undergo a chemokine receptor switch, with down-regulation
      of inflammatory chemokine receptors followed by induction of CCR7. These
      temporally coordinated events allow DC to leave tissues and to localize in
      lymphoid organs by responding to CCR7 agonists. DC are also present in tumors
      that produce chemokines, but their significance remains to be defined. In
      addition to responding to chemokines, DC are a major source of certain chemokines
      such as macrophage-derived chemokine. The interaction of DC with chemokines is
      essential to the function of these cells in normal and pathological conditions
      and may provide tools for novel therapeutic strategies.

PMID- 10941825
TI  - Human immunodeficiency virus type 1 replication, immune activation, and
      circulating cytotoxic T cells against uninfected CD4+ T cells.
AB  - Cytotoxic T lymphocytes (CTL) that kill uninfected activated CD4+ T cells can be
      induced in vitro by stimulating CD8+ T cells with activated autologous CD4+ T
      cells. Similar CTL have been detected in circulating T cells from human
      immunodeficiency virus type I (HIV)-infected individuals. To define the in vivo
      correlates of this CTL activity, we studied plasma beta-2 microglobulin and HIV
      RNA levels, T-lymphocyte subset counts, and expression of CD28 on CD8+ T cells
      concurrently with circulating CTL activity against uninfected CD4+ T cells in 75
      HIV-infected individuals at different stages of disease progression. Mean values
      of each parameter were compared in subsets of this group of 75 segregated on the
      basis of this CTL activity. The group with CTL against uninfected activated CD4+
      T lymphocytes had more CD8+ T cells, a higher percentage of CD28 CD8+ T cells,
      and higher plasma levels of HIV RNA and beta-2 microglobulin. CTL against
      uninfected activated CD4+ T cells were predominantly CD28 and in HIV-infected
      individuals were associated with immunological or virological evidence of
      progressive disease. In HIV infection, circulating CTL activity against
      uninfected activated CD4+ T lymphocytes is associated with immune activation,
      CD8+ T cell expansion, accumulation of CD28 CD8+ T cells, and inadequate
      suppression of HIV replication.

PMID- 10941824
TI  - Active immunization of humans with dendritic cells.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells specialized to initiate
      T-cell immunity. The development of methods to generate large numbers of DCs has
      facilitated their application for immunotherapy. Recent studies have demonstrated
      the safety and immunogenicity of DCs in humans and have begun to outline the
      durability, kinetics, and nature of the elicited T-cell responses. However, DC
      based immunotherapy remains a challenge and several parameters need to be
      examined to optimize immune responses, in order to maximize clinical efficacy
      against cancer and infectious diseases.

PMID- 10941826
TI  - Immune response of SLE patients to peptides based on the complementarity
      determining regions of a pathogenic anti-DNA monoclonal antibody.
AB  - We have examined the humoral and cellular responses of SLE patients to peptides
      based on the complementarity-determining regions (CDR) of a monoclonal anti-DNA
      antibody with a major idiotype- 16/6 Id, in comparison to their responses to the
      whole 16/6 Id-bearing antibody. Sera of 63% of the SLE patients had antibodies
      that bound the 16/6 Id, 80% had antibodies to one of the CDR-based peptides, and
      40% of the patients reacted with both CDRs. Sera of only a few controls reacted
      with either the 16/6 Id (6%) or the CDR based peptides (4%) (P < 0.01).
      Peripheral blood lymphocytes (PBL) of 39% of the patients proliferated in
      response to the 16/6 Id or to one of the CDR-based peptides (37%), while in the
      control group the proliferation rates were 66% to the 16/6 Id and 59% to one of
      the CDR-based peptides (P < 0.05). The correlation between (both) the humoral and
      cellular immune responses to the CDR-based peptides and to the 16/6 Id suggests
      the relevance of these peptides to the 16/6 Id and provides additional
      information on the pathogenic moiety of the latter antibody.

PMID- 10941828
TI  - Antigen-specific regulation of CD1 expression in humans.
AB  - During the last decade the CD1 family of cell surface glycoproteins has been
      implicated in the presentation of nonpeptide antigens in man. Recent findings by
      our group indicate that CD1 molecules also can be involved in the presentation of
      certain bacterial proteins. However, CD1a, b, and c (group 1 CD1 molecules) are
      not present at significant levels on circulating monocytes unless their
      expression is induced by cytokines such as granulocyte-macrophage colony
      stimulating factor (GM-CSF). In this study we investigated the cell surface
      expression of CD1 molecules following the antigenic stimulation in vivo via
      immunization of healthy volunteers with tetanus toxoid vaccine and in vitro cell
      cultures using the same antigen. Both the in vivo and in vitro studies
      demonstrated clear up-regulation of the surface expression of CD1a, b, and c on
      monocytes as a result of antigenic stimulation with tetanus toxoid, supporting
      the idea that CD1 molecules participate in the presentation of this protein
      antigen in man. In vitro, antigen-triggered expression of these molecules was
      mediated by GM-CSF, since neutralization of this cytokine with specific antibody
      totally abrogated CD1a, b, and c expression. In contrast to the group 1 CD1
      molecules, CD1d was found to be constitutively expressed on the majority of
      circulating monocytes and B lymphocytes prior to immunization. There was no
      effect of antigenic stimulation with tetanus toxoid on the cell surface
      expression of CD1d, suggesting major differences in regulation of the expression
      and function of the different CD1 molecules in humans. Altogether our results
      point to antigen-driven up-regulation of CD1a, b, and c expression on human
      monocytes that is mediated by GM-CSF and no effect on CD1d expression.

PMID- 10941827
TI  - Cytotoxic T-lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA
      vaccination.
AB  - We recently have reported that Wilms' tumor gene WT1 is highly expressed not only
      in leukemias but also in various types of solid tumors and that WT1 protein is a
      novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited
      by immunization with 9-mer WT1 peptides capable of binding to major
      histocompatibility complex (MHC) class I molecules. In the present study, plasmid
      DNA encoding murine full-length WT1 protein was injected intramuscularly into
      C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against
      the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a
      MHC class I-restricted manner. Furthermore, the vaccinated mice rejected the
      challenges of WT1-expressing tumor cells and survived with no signs of
      autoimmunity caused by the CTLs. These results demonstrated that vaccination with
      the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein,
      resulting in the acquisition of rejection activity against challenges of WT1
      expressing tumor cells. This WT1 DNA vaccination may find clinical application
      for various types of solid tumors as well as leukemias.

PMID- 10941829
TI  - Elevation of IL-18 in human sepsis.
AB  - Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine that
      shares biochemical features with IL-1beta and acts in part by inducing interferon
      gamma (IFN-gamma). Endotoxic bacterial lipopolysaccharide (LPS) (1 or 2 ng/kg)
      was insufficient to increase plasma IL-18 in five healthy adults measured 3, 12,
      and 24 hr following challenge. In contrast, in the first 96 hr of admission to
      the surgical intensive care unit, mean maximal serum IL-18 was elevated (1,122 +/
      259 pg/ml) in nine septic patients compared to six healthy adults (191 +/- 42
      pg/ml), P < 0.01). Serum IL-18 concentrations in septic patients did not
      correlate with other measured inflammatory mediators: tumor necrosis factor, IL
      6, IL-10, or secretory leukocyte protease inhibitor. Therefore, IL-18 circulates
      in healthy adults and is a component of the human systemic inflammatory response.
      Further, stimuli other than LPS may induce IL-18 production in vivo in human
      sepsis.

PMID- 10941832
TI  - Sample sequencing of the human major histocompatibility complex class I region
      identifies further new genes.
AB  - We used sample sequencing, a technique which generates random genomic sequence
      from cosmid clones and compares them with sequences deposited in the GenBank
      databases, to identify new genes in the class I region of the human major
      histocompatibility region. We isolated and ordered cosmid clones from a flow
      sorted chromosome (Chr) 6 cosmid library, generating cosmid contigs covering
      approximately one third of the HLA class I region. Fifteen of these cosmids were
      then sample sequenced. A total of 216,694 bp of genomic sequence was generated
      and compared with sequences deposited in GenBank databases. In addition to
      identifying established class I region genes, a number of potential new genes
      were identified, including several which were not included in the recent major
      histocompatibility complex (MHC) consensus sequence map. Of particular interest
      are several new transcripts in the psoriasis susceptibility region.

PMID- 10941831
TI  - Antioxidative capacity in patients with common variable immunodeficiency.
AB  - Highly reactive oxygen species (ROS) are involved in T-cell activation and in the
      defense against environmental pathogens. An imbalance of ROS generation,
      detoxifying scavenger enzymes, and molecules with antioxidant capacity could
      contribute to the increased susceptibility to cancer and infections in severe
      humoral immunodeficiency. We studied antioxidant status, i.e., plasma antioxidant
      capacity (TEAC), retinol, alpha-to-copherol, ubiquinol, and the number of
      activated T cells in 16 patients with common variable immunodeficiency (CVID)
      compared to age-matched healthy controls. As expected, patients showed
      significantly increased levels of activated HLA-DR and CD45RO-expressing T cells.
      Plasma levels of the endogenous ROS scavenger ubiquinol (Q 10) were significantly
      lower in patients as compared to controls. However, patients showed only slightly
      reduced levels of TEAC as well as the exogenous antioxidants retinol and alpha
      tocopherol. Although no correlation of the number of activated T cells and
      antioxidant capacity could be demonstrated, an increase in ROS and a diminished
      reactive oxygen scavenger capacity may be involved in the disease process in
      patients with common variable immunodeficiency.

PMID- 10941830
TI  - The [HLA-B18, F1C30, DR3] conserved extended haplotype carries a susceptibility
      gene for IgD deficiency.
AB  - We showed previously that the conserved extended MHC haplotype [HLA-B8, SCO1,
      DR3] carries recessive susceptibility genes for IgA and IgG4 deficiency and
      dominant genes for IgD and IgG3 deficiency. [HLA-B18, F1C30, DR3] has similar
      class II and III regions to [HLA-B8, SC01, DR3] and is common in the Basques. We
      therefore studied serum immunoglobulin concentrations in Basque homozygotes,
      heterozygotes, and noncarriers of (FIC30, DRB1*0301, DRB3*02, DQA1*0501.
      DQB1*0201) (F1C30, DR3). As shown by others, no subjects were deficient in IgA,
      IgM, or IgG subclasses. In contrast, 29% of homozygotes and three of seven double
      heterozygotes with (SC01, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201) (presumed
      homozygotes for IgD deficiency susceptibility genes) were IgD deficient. Thus,
      32% of presumed homozygotes were IgD deficient compared with 1.6% of noncarriers.
      Of haplotype heterozygotes, 25% were IgD deficient. The high frequency of IgD
      deficiency in both homozygotes and heterozygotes for (F1C30, DR3) suggests a
      partially penetrant dominant susceptibility gene for IgD deficiency on [HLA-B18,
      F1C30, DR3].

PMID- 10941833
TI  - Impaired expression of MHC class I molecules on mouse testicular germ cells is
      mainly caused by the post-transcriptional mechanism.
AB  - In this study, we examined expression of the major histocompatibility complex
      (MHC) class I molecules and of the mRNAs for MHC class I-mediated antigen
      presentation machinery molecules in highly purified C57BL/6 mouse testicular germ
      cells. Although H2 class I molecules were not detected on the cell surface, small
      amounts of the molecules were detected inside the cells by flow cytometric and
      immunoprecipitation analyses. Interferon (IFN)gamma treatment did not affect
      expression of the molecules on the surface by flow cytometric analysis. In
      addition, expression of mRNAs for MHC class I-mediated antigen presentation
      machinery molecules in the germ cells was analyzed by reverse transcription
      polymerase chain reaction analysis. The faint constitutive expression of mRNAs
      for H2-K, beta2-microglobulin (beta2m), tapasin, and calnexin was observed in the
      cells. IFNgamma treatment up-regulated expression of mRNAs for H2-K, beta2m, TAP1
      (a peptide transporter), and LMP2 (a proteosomal subunit). These findings
      indicate that impaired expression of MHC class I molecules on the cell surface of
      mouse testicular germ cells is mainly caused by the post-transcriptional
      regulatory mechanism.

PMID- 10941834
TI  - Genetics of atopy in a mouse model: polymorphism of the IL-5 receptor alpha
      chain.
AB  - To study the genetics of atopy systematically we established a mouse model that
      provides the general phenotype of atopy: the early response characteristic of IgE
      dependent eczema or atopic dermatitis, and the diagnostic test of atopy, the skin
      prick test. Using an immediate cutaneous hypersensitivity test (ICHS) against
      birch pollen extract we could classify A/J and C57BL/6 (B6) inbred mouse strains
      respectively as high responder and low responders. The F1 hybrids were found to
      be high responders with incomplete penetrance. Backcrossing F1 mice to the low
      responder B6 strain yielded three classes of responders, high, intermediate, and
      low. A genome-wide microsatellite screen of the backcross progeny disclosed
      suggestive linkage to a microsatellite marker on chromosome 6 close to the locus
      of the IL-5 receptor alpha chain. Its allelic variation in A/J and B6 strains was
      investigated and two major differences were detected. Firstly, a nucleotide
      exchange in the 5' untranslated region of B6 mRNA resulted in increased
      transcription/translation of a reporter construct. Higher expression of the
      receptor on the cell surface would be expected to favor an allergic immune
      response. Secondly, the two alleles are differentially spliced so as to yield two
      soluble isoforms in A/J mice versus one in B6 mice. Higher expression of soluble
      IL-5R would be expected to reduce the level of allergy through capture of IL-5.
      Thus both findings conform to the expectation based on susceptibility to atopy
      and thus identify the IL-5R alpha chain as a likely contributor to the genetics
      of atopy.

PMID- 10941835
TI  - Genes encoding human killer-cell Ig-like receptors with D1 and D2 extracellular
      domains all contain untranslated pseudoexons encoding a third Ig-like domain.
AB  - Human killer-cell immunoglobulin-like receptors (KIR) show three types of
      organization of their extracellular domains: D0-D1-D2 in KIR3D, D1-D2 in the
      majority of KIR2D, and D0-D2 in KIR2DL4 and the novel KIR2DL5. The gene for a
      KIR2DL3 variant, which has a D1-D2 structure, has been shown previously to have a
      nonexpressed region (pseudoexon 3) that is paralogous to the exon encoding the D0
      domain of other KIR. This pseudoexon is not expressed because it is skipped
      during splicing of pre-mRNA. In this study, we demonstrate that all eight genes
      encoding human KIR with D1-D2 configuration (KIR2DL1-KIR2DL3, KIR2DS1-KIR2DS5)
      have similarly untranslated pseudoexons. Whereas the pseudoexons of four of these
      KIR genes bear nonsense mutations and/or altered splicing sites, the pseudoexons
      in the other four KIR genes have no major structural abnormalities, indicating
      that other mechanisms are responsible for inactivation of their exons 3. A
      comparison of the sequences on pseudoexons 3 with the paralogous expressed exons
      suggests that an exonic splicing enhancer may be necessary for the expression of
      exon 3 in KIR genes.

PMID- 10941837
TI  - Genomic organization of the human leukocyte immunoglobulin-like receptors within
      the leukocyte receptor complex on chromosome 19q13.4.
AB  - The leukocyte immunoglobulin (Ig)-like receptors (LIRs) comprise a family of cell
      surface receptors that couple to either activating or inhibitory signals
      depending on the nature of their transmembrane and cytoplasmic domains. We
      describe the organization and fine localization of the genes for LIR-1 and LIR-5,
      which are inhibitory receptors, and LIR-6, which is an activating receptor. The
      genomic organization of all three genes is highly conserved from the signal
      peptide through the membrane-proximal Ig domain but diverges thereafter depending
      on the inhibitory or activating nature of the gene product. The 3' untranslated
      region of the gene for LIR-6 contains a 37-base pair repeat not present in the
      LIR-1 or LIR-5 genes. 5' rapid amplification of cDNA ends defined the putative
      transcription initiation site of the LIR-5 gene, which is TATA-less. A nucleotide
      substitution in the LIR-5 gene led to loss of an intron present in the 5'
      untranslated region of the LIR-1 and LIR-6 genes. Differences in the genomic
      structure of these three LIR genes suggests possible mechanisms for their
      differential expression in cells of hematopoietic lineage. The three genes are in
      a region of Chromosome 19q13.4 that is immediately centromeric of the killer cell
      Ig-like receptor genes and are separated from one another by approximately 20 to
      30 kb, suggesting that they arose by gene duplication from a common ancestor.

PMID- 10941836
TI  - Transcriptional enhancers of immunoglobulin light chain genes in Atlantic cod
      (Gadus morhua).
AB  - The organization of immunoglobulin heavy (H) chain genes in teleosts resembles
      that of mammals and amphibians, whereas light (L) chain genes are arranged in
      multiple clusters of variable (VL), joining (JL), and constant (CL) region
      segments. Sequence analysis of two Atlantic cod genomic clones (14,966 and 13,116
      bp in length) revealed a very compact IgL chain locus with the VL genes in
      opposite transcriptional orientation to the JL and the CL genes. This suggests
      the possibility of rearrangements between clusters by inversion. Each cluster
      spans approximately 2.1 kb and distances between clusters vary between 2.1 and
      4.8 kb. To gain insight into the transcriptional regulation of this complex,
      multiclustered locus, chloramphenicol acetyl transferase reporter constructs
      containing 14 different DNA segments from the two genomic clones were transfected
      into channel catfish B and non-B-cell lines, as well as into mouse B-cell lines.
      These studies showed strong enhancer activity downstream of the CL region in
      three out of six L chain gene clusters when assayed in fish, but not in mouse B
      cells. Interestingly, both mouse and human lambda enhancers exhibited strong
      activity in the fish B cells, while the mouse 3' kappa enhancer did not. This
      suggests that transcription factors similar to those involved in mammalian lambda
      expression are present in B cells from teleosts.

PMID- 10941838
TI  - Variable region diversity of the Atlantic cod (Gadus morhua L.) immunoglobulin
      heavy chain.
AB  - This study was undertaken to determine whether a lack of VH domain diversity
      could explain, in part, the failure of Atlantic cod to respond to immunization
      with the production of specific antibodies. The variability of cod VH regions was
      studied in 113 cDNA and 2 genomic clones. A fourth VH family and a second
      putative JH element were identified. The expressed VH repertoire showed a clear
      bias in the pattern of VH family utilization, with about 80% of the clones
      belonging to the VH-III family. Furthermore, the VH-III family was complex and
      could be subdivided into several subfamilies, while little variation was seen
      within the other families. The VH family bias gives a somewhat reduced
      variability of the VH gene region of cod, but not lower than that of the rabbit
      IgM repertoire. The H chain CDR3 region of cod was longer than that of trout,
      frog and mouse, and also highly variable in sequence, probably reflecting a
      relative importance of this region in cod. On the other hand, the CDR3 length
      variability was restricted, and this may reduce the diversity of the cod VH
      region.

PMID- 10941839
TI  - RAG expression is restricted to the first year of life in the Mexican axolotl.
AB  - The developmental expression of the RAG1 gene in the Mexican axolotl
      hematopoietic organs was studied. RAG1 mRNAs were first detected in trunk
      extracts from 6-week-old larvae, and in head and trunk extracts of 8- and 9-week
      old larvae. RAG1 is expressed in the thymus at all stages of development, until
      its natural involution after 12 months of age. In contrast, although RAG1
      transcripts were present in the spleen and liver of the young larvae, they were
      not detected in the liver after 4.5 months and in the spleen after 8 months. No
      RAG1 mRNA expression was observed in the spleens or livers of 24-month-old
      hyperimmunized axolotls. The developmental expression of the RAG2 protein was
      also analyzed in axolotl thymus, spleen, and liver extracts using specific anti
      RAG2 antibodies. RAG2 was readily detected at 7 months, but not in hematopoietic
      organs of 12- and 24-month-old axolotls. The presence of RAG1 transcripts was
      limited to the sub-capsular area of the thymus lobes, as detected by in situ
      hybridization. Discrete clusters of labeled cells were observed in the spleen
      sections, and a relatively large number of labeled cells were located in the
      hepatic peripheral hematopoietic layer of 3-month-old axolotls. The first
      appearance of RAG1 gene products in the axolotl hematopoietic organs is thus well
      correlated with the first production of rearranged T-cell and B-cell receptor
      mRNAs, 40-60 days after fertilization.

PMID- 10941840
TI  - Quantitative analysis of XG blood group and CD99 antigens on human red cells.
AB  - CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative
      polymorphism co-regulated with the Xga blood group polymorphism. The co
      expression of X-linked MIC2 and XG genes is presumably controlled at the
      transcriptional level by a single XGR locus in the pseudoautosomal region of
      sexual chromosomes. This locus is composed of two alleles, XGR(low) and
      XGR(high), which determine low or high CD99 levels (CD99-L, CD99-H) and the Xg(a
      )/ Xg(a+) status. To test this hypothesis, the phenotypic relationship between
      Xga and CD99 antigens on human RBCs was investigated by quantitative flow
      cytometry using NBL-1 (anti-Xga) and 12E7 (anti-CD99) monoclonal antibodies and
      semi-quantitative estimate of membrane proteins and RNA by Western blot and
      Northern blot, respectively. The antibody binding capacity of RBCs, which is an
      estimation of the antigen density, was determined for 118 blood donors including
      60 males and 58 females. Xg(a+) RBCs, which all belong to the group of CD99-H
      expressors, carry 159+/-13 and 960+/-50 copies of Xga and CD99 molecules/cell,
      respectively. Xg(a-) RBCs have no Xga antigen, but are subdivided into CD99-H
      (all male) and CD99-L expressors carrying 747+/-28 and 200+/-22 CD99 copies/cell,
      respectively, with identical CD99 levels between CD99-L males and females.
      However, among males, the CD99 expression was higher in Xg(a+) than in Xg(a
      )/CD99-H individuals (P<0.01). In addition, CD99-H expressors in Xg(a+) males
      could be clearly subdivided into two categories, high and super high expressors,
      which are presumably heterozygous and homozygous for the XGR(high) allele, which
      fits the above hypothesis. This was not the case for Xg(a+) females where CD99-H
      subcategories were not found. Quantitative differences were confirmed by Western
      blot analysis of red cell membrane preparations from individuals of different Xga
      and CD99 phenotypes and by Northern blot analysis showing that the reticulocytes
      from CD99-L individuals expressed a reduced level of MIC2 transcripts compared to
      CD99-H donors. These findings further support the hypothesis of a single genetic
      control of CD99 and Xga expression by the XGR locus.

PMID- 10941841
TI  - Evidence for association and linkage between atopy, airway hyper-responsiveness,
      and the beta subunit Glu237Gly variant of the high-affinity receptor for
      immunoglobulin E in the French-Canadian population.
AB  - Following detection of linkage between atopy and chromosome 11q13 markers,
      association between this disorder and variants of the beta subunit of the high
      affinity receptor for immunoglobulin E (FcepsilonRI-beta, a candidate gene for
      asthma-related conditions co-localizing within the same region) was reported in
      Australian, British and Japanese populations. Investigations in several other
      ethnic groups failed to replicate these observations. Due to the complexity of
      defining intermediate phenotypes related to asthma, detection of such
      associations may have been hampered by clinical misclassifications. To assess
      whether the FcepsilonRI-beta gene was involved in atopy and/or airway
      hyperresponsiveness (AHR) in the French-Canadian population, we conducted a case
      control study in 200 subjects using strict criteria for asthma and related
      conditions. The Ile181Leu and Glu237Gly FcepsilonRI-beta sequence variants were
      tested exploiting two amplification refractory mutation systems. No association
      was detected between atopy or AHR and the Ile181Leu FcepsilonRI-beta variant.
      However, a strong association was observed between atopy and the Glu237Gly
      FcepsilonRI-beta variant (odds ratio=12.25). Four large Eastern Quebec families
      (n=106 subjects) were also recruited to perform a genetic linkage study. We
      observed suggestive evidence of linkage between atopy and the Glu237Gly
      FcepsilonRI-beta variant (Zmax=2.30). This study is the first to detect the
      presence of an association between atopy and the Glu237Gly FcepsilonRI-beta
      variant in French-Canadians. Our data suggest that a susceptibility locus for
      atopy is located on chromosome 11q13 in this population.

PMID- 10941842
TI  - Extensive gene duplications and a large inversion characterize the human
      leukocyte receptor cluster.
AB  - The chromosomal region 19q13.4 harbors the human leukocyte receptor cluster (LRC)
      which has been demonstrated to contain 19 genes encoding leukocyte-expressed
      receptors of the immunoglobulin (Ig) superfamily. A spotted PAC library was used
      to construct a contig of 65 overlapping clones spanning the complete LRC. Within
      the 900 kb covered by the contig, we identified one cluster containing killer
      cell inhibitory receptor genes and two clusters containing Ig-like transcript
      (ILT) genes. Of these, the second ILT cluster, located at the centromeric end of
      the LRC, was previously unknown. Detailed analysis of the ILT receptor genes in
      this cluster revealed one novel (ILT11) and six already known ILT genes. The two
      ILT clusters are transcribed in opposite directions and are separated by about
      200 kb, which contains two leukocyte-associated inhibitory receptor (LAIR) genes.
      The data suggest that the two ILT clusters, each including one LAIR locus, arose
      from a single ancestral ILT/LAIR cluster by inverse duplication of a c large
      genomic fragment. Furthermore, the NK cell-expressed NKp46 gene was localized 20
      kb telomeric of FCAR; and 14 novel genes mapping within the LRC were identified
      by cDNA selection. Together with the gene for the ribosomal protein S9 (RPS9),
      which had previously been assigned to 19q13.4, the total number of LRC genes is
      now 44. Of these, 29 belong to the Ig superfamily.

PMID- 10941843
TI  - Sequence and diversity of the rat delta T-cell receptor.
AB  - The cDNA sequence of the delta T-cell receptor (TCRD) in the adult Lewis rat
      thymus was determined using the technique of rapid amplification of cDNA ends.
      Sixteen variable region genes (TCRDV), two diversity regions (TCRDD), two joining
      regions (TCRDJ), and a single constant region gene (TCRDC) were identified. The
      sixteen unique TCRDV genes identified represented eight different subfamilies in
      the rat and were highly conserved (>80% nucleotide identity) to corresponding
      mouse sequences. Extensive junctional diversity was observed in the rat, with
      both TCRDD regions (TCRDD1 and TCRDD2) utilized in the majority of cDNA clones
      identified. The two TCRDJ genes were highly conserved and corresponded to TCRDJ1
      and TCRDJ2 in the mouse; the majority of clones utilized TCRDJ1. The TCRDC region
      in the rat was 91.1% identical to the mouse TCRDC gene and was highly conserved
      to other species. Although extensive sequence information about mouse gamma-delta
      T-cell receptor genes is available, current knowledge of rat gamma-delta T-cells
      is limited. The sequence analysis presented in this study adds to our
      understanding of gamma-delta T-cells in general, and it may be utilized to study
      the role of gamma-delta T-cells in immune-mediated disease and transplantation
      models previously established in the rat.

PMID- 10941844
TI  - Expression and cellular localization of the protein encoded by the 1C7 gene: a
      recently described component of the MHC.
AB  - The major histocompatibility complex (MHC) is located on human Chromosome 6 and
      includes clusters of class I, class II, and class III genes. Centromeric to the
      class I region is a cluster of genes designated as MHC class IV encoding genes
      involved in immunity and inflammation, including the 1C7 gene. The human 1C7 gene
      has several alternatively spliced forms and potentially codes for proteins with
      at least three unique carboxy termini. 1C7 mRNA in human (h1C7) is present in
      spleen, tonsil, B and NK cell lines, and with a different splicing pattern in
      liver. The 1C7 RNA and protein are present at highest levels in the germinal
      center of the lymphoid follicles in tonsil. The protein is expressed in NKL
      cells, tonsil, and unexpectedly in brain. In contrast, the mouse 1C7 gene is
      transcribed in liver but is predicted to be a pseudogene. However, the 1C7
      homologue expressed in rat is predicted to have long stretches of amino acids
      essentially identical to the human protein.

PMID- 10941845
TI  - Selection of T-cell epitopes from foot-and-mouth disease virus reflects the
      binding affinity to different cattle MHC class II molecules.
AB  - The major histocompatibility complex (MHC)-restricted selection of T-cell
      epitopes of foot-and-mouth disease virus (FMDV) by individual cattle MHC class II
      DR (BoLA-DR) molecules was studied in a direct MHC-peptide binding assay. By in
      vitro priming of T lymphocytes derived from animals homozygous for both MHC class
      I and II, five T-cell epitopes were analyzed in the context of three MHC class II
      haplotypes. We found that the presentation of these T-cell epitopes was mediated
      by DR molecules, since blocking this pathway of antigen presentation using
      monoclonal antibody TH14B completely abolished the proliferative responses
      against the peptides. To study the DR-restricted presentation of these T-cell
      epitopes, a direct MHC-peptide binding assay on isolated cattle DR molecules was
      developed. Purified cattle MHC class II DR molecules of the BoLA-DRB3*0201, BoLA
      DRB3*1101, and BoLA-DRB3*1201 alleles were isolated from peripheral blood
      mononuclear cells. For each allele, one of the identified T-cell epitopes was
      biotinylated, and used as a marker peptide for the development of a competitive
      MHC-peptide binding assay. Subsequently, the T-cell epitopes of FMDV with
      functionally defined MHC class II specificity were analyzed in this binding
      assay. The affinity of the epitopes to bind to certain DR molecules was
      significantly correlated to the capacity to induce T-cell proliferation. This
      demonstrated at the molecular level that the selection of individual T-cell
      epitopes found at the functional level was indeed the result of MHC restriction.

PMID- 10941846
TI  - Association of the interleukin-4 receptor alpha variant Q576R with Th1/Th2
      imbalance in connective tissue disease.

PMID- 10941847
TI  - Molecular basis of antigenic differences between the RT7 alleles of rat CD45.

PMID- 10941848
TI  - Rfp-Y genotype affects the fate of Rous sarcomas in B2B5 chickens.

PMID- 10941849
TI  - A novel alloreactivity-controlling locus, Alan1, mapped to mouse chromosome 17.

PMID- 10941850
TI  - Polymorphism in the 2B4 gene of inbred mouse strains.

PMID- 10941851
TI  - Detection of a polymorphism in exon 8 of the human CD86 gene.

PMID- 10941852
TI  - Aims in the management of gastroesophageal reflux disease: a gastroenterologist's
      viewpoint.
AB  - Relieving heartburn and healing esophagitis may appear to be primary aims in the
      management of gastroesophageal reflux disease, but systematic consideration of
      the issues demonstrates that there are discrepancies between the fundamental aims
      of medical management and the aims selected for study in trials of drug efficacy.
      The initial aims of management are those concerned with diagnosis, patient
      assessment and the provision of explanation and advice. The therapeutic
      objectives are alleviating symptoms, preventing complications and, if possible,
      avoiding recurrence, and should ideally be judged in terms of health gain,
      including quality of life improvement. Obtaining value for money, by maximizing
      the health gain in relation to the cost of the overall medical intervention must
      also be acknowledged as a desirable aim of management, with the proviso that
      physicians must always treat each patient as an individual and individualize
      clinical management appropriately.

PMID- 10941853
TI  - Revisional surgery after colon interposition for benign oesophageal disease.
AB  - Although the short-term results of colon interposition for replacement of the
      oesophagus in part or as a whole are known to be satisfactory, there have been
      several reports of functional problems associated with total replacement in the
      long-term follow-up of patients. We have retrospectively studied patients who
      have required revisional surgery for anatomical and functional sequelae over a 7-
      to 38-year period. Although the short-segment colon interpositions have been
      relatively trouble free, several mechanical and functional problems requiring
      revisional surgery have been encountered in the long-term follow-up of patients
      who underwent long-segment colon interposition.

PMID- 10941854
TI  - Functional evaluation of the ileocolic sphincter transplanted to the neck using
      microsurgery technique: a manometric study in dogs.
AB  - The usefulness of ileocolic sphincter (ICS) transplantation to the neck after a
      total laryngopharyngectomy was investigated in 12 mongrel dogs. The authors aimed
      to evaluate the influence of the transplantation on ICS pressure amplitude and
      ICS length, and on ICS resistance to intracecal pressure increase.
      Electromanometric measurements showed that ICS pressure amplitude and length
      presented no changes after the procedure. Also, there was no significant change
      in ICS resistance. However, long-term follow-up studies are needed to determine
      whether the ileocolic transition maintains the properties observed in the
      immediate postoperative period.

PMID- 10941855
TI  - The stapled, uncut gastroplasty for hiatal hernia: 24 years' follow-up.
AB  - A simple, tension-free, in situ gastroplasty was devised in the late 1960s and
      early 1970s to avoid the recurrences and complications of the Collis and Nissen
      hiatal hernioplasties. Long-term follow-up has now been completed on 153
      patients. For this procedure, the anterior gastric wall is stapled, not cut, and
      the fundoplication is performed on the cardia and the neoesophagus created by the
      stapling and is sutured under the diaphragm. A total of 161 patients underwent
      the stapled, uncut gastroplasty and were followed for up to 24 years. Conditions
      included reflux in 145, organic stricture in 23, giant hiatal hernia in 14 (with
      or without obstruction) and collagen esophagus in six. Post-operative tests
      included subjective symptom evaluation by questionnaire, esophageal manometry and
      24-h pH monitoring. Of the total 161 patients, 89 were followed up for 2-10 years
      and 64 for 1-24 years; seven were lost to follow-up and one died soon after the
      operation. The stapled, uncut gastroplasty and fundoplication produced 95%
      excellent and good results (Matthews classification grade I and II). After the
      procedure, the esophagus was significantly lengthened (from 2.55 +/- 0.96 to 3.2
      +/- 0.32 cm; p < 0.001) and sphincter pressure was significantly increased (from
      6.35 +/- 3.5 to 27.3 +/- 6.82 mmHg; p < 0.0001). No leakage, bleeding, or
      'slipped' recurrence was observed. Only one patient experienced dissolution of
      the wrap and recurrent symptoms. Aspiration, scleroderma, stricture and short
      esophagi, post-gastrectomy gastric remnants and hiccups were treated with
      excellent and good long-term results. The stapled, uncut gastroplasty has
      universal application with excellent results, not only in typical cases of
      gastroesophageal reflux, but also in complicated situations such as short
      esophagus, strictures, or dysperistaltic and aperistaltic esophagus.

PMID- 10941856
TI  - Prognostic value of the lower esophageal sphincter gradient and acid exposure in
      the follow-up of antireflux operations.
AB  - Eighty-eight consecutive patients with antireflux fundoplication had manometry
      and pH recording pre- and post-operatively at 6 months and 1, 3 and 5 years for a
      mean follow-up of 30.6 months. Failure occurred in nine patients (11.4%). For the
      whole group of patients, surgery produced a significant increase in the lower
      esophageal sphincter (LES) pressure gradient from 9.5 +/- 6.3 to 14.6 +/- 6.7
      mmHg and a significant decrease in acid exposure from 20.6% +/- 17.6% to 5.5% +/-
      8.8% at 6 months. There was a similar change in pressure (p < 0.0005) and pH (p <
      0.002) in the successful but not in the failure group. Over time, the values
      remained stable in both groups. Post-operative LES pressure was significantly
      correlated with the outcome at 6 months (p < 0.02), and the pH was inversely
      correlated at 5 years (p < 0.039). This study confirms the early predictive value
      of the post-operative LES pressure. Esophageal acid exposure remains a reliable
      marker of the outcome. However, recurrences remain unexplained by LES pressure
      measurement and long-term follow-up using manometry and pH recording does not
      bring additional valuable data.

PMID- 10941857
TI  - The endoscopic treatment of benign esophageal strictures by balloon dilatation.
AB  - Benign strictures of the esophagus are serious illnesses that have a great
      adverse effect on the quality of life of patients. There are several methods of
      treatment. In this study the endoscopical balloon dilatation technique was used.
      All dilatations were performed under analgosedation, and plastic balloons (6-25
      mm) were used. Ninety dilatations were performed between 1995 and 1997. Twenty
      two patients were diagnosed as having benign stenosis of the esophagus. We
      evaluated the effectiveness and the complication rate of the method. All patients
      except two showed immediate improvement: 59% were cured; 18% had at least one
      recurrence of the stenosis; 9% had improvement but treatment continues; 14%
      required other treatment. We encountered two cases with major complications, i.e.
      perforation. Balloon dilatation seems to be an effective and safe method for
      treatment of the benign esophageal strictures and is well tolerated by patients.
      Endoscopic control is sufficient, and radiographic control is not required.
      Randomized prospective studies are needed to establish the role of this method in
      comparison with other treatments.

PMID- 10941858
TI  - Laparoscopic myotomy in achalasia: intraoperative evidence for myotomy of the
      gastric cardia.
AB  - The myotomy performed for achalasia of the esophagus should divide all of the
      constricting, diseased muscular elements that obstruct the esophagogastric
      junction (EGJ). Whether the disease process includes proximal gastric as well as
      esophageal components is as yet unclear, but anatomic evidence complemented by
      clinical data suggest that the disease process does not end at the evanescent and
      poorly defined EGJ. Clinical reports from enthusiastic proponents of a particular
      operative approach for achalasia have not been illuminating in this regard,
      because all patients are improved to some degree post-operatively, and there are
      no objective parametric standards for the evaluation of swallowing function. This
      study reports a series of patients in whom endoscopic viewing was used to judge
      the adequacy of myotomy after 'esophageal' myotomy. The question posed by this
      study was, 'Does esophageal myotomy remove all constricting elements at the
      gastroesophageal junction?' Laparoscopic myotomy was performed in 48 patients
      with a diagnosis of achalasia; these patients are the most recent in a total
      cohort of 72 patients operated upon for achalasia during the past 20 years.
      Myotomy was begun on the esophagus, and extended to the esophagogastric junction;
      anatomic landmarks, including the appearance of submucosal veins, guided the
      initial dissection. Intraoperative endoscopy was then performed to determine
      whether there was residual constriction of the channel between the esophagus and
      stomach; if so, myotomy was extended onto the gastric cardia until visual
      evidence of obstruction had disappeared. All patients had either Toupet
      fundoplication or Dor fundoplication after myotomy. There were obvious
      constricting elements distal to the gastroesophageal junction in 90% of the
      patients. These patients required extension of the myotomy onto the stomach for
      an average of 15 mm. All but one patient had improved swallowing post
      operatively. Eight patients required 'stretch' of the distal esophagus/cardia
      within the first year post-operatively; one patient was reoperated for fibrous
      scar obstruction of the distal esophagus. Esophageal myotomy limited to the
      esophageal muscle does not remove all constricting elements at the
      gastroesophageal junction; as a result, the extended myotomy must be complemented
      by an antireflux procedure during operations for achalasia.

PMID- 10941859
TI  - Echoendoscopic evaluation of botulinum toxin intrasphincteric injections in
      Chagas' disease achalasia.
AB  - Botulinum toxin (BT) has recently been indicated as an alternative treatment of
      idiopathic achalasia with a success rate of 60-70%. One-third of BT-treated cases
      either fail to respond or fail to sustain the response beyond 6 months. An
      explanation for BT therapeutic failure would be that the lower esophageal
      sphincter muscular layer (LES) may be missed as injection is delivered 'blindly'.
      We aimed to evaluate the percentage of exact endoscopically 'blind' LES punctures
      using echoendoscopy after the injection of BT for the treatment of Chagas'
      achalasia (CA). Five patients with CA (mean age 53 years) were randomized to
      receive 1.2 ml of BT or the same amount of saline injected endoscopically.
      Echoendoscopy was performed immediately after puncture. Patients were evaluated
      by the clinical score of dysphagia, radiological examination, upper endoscopy and
      esophageal manometry and followed up for 6 months. All puncture sites were
      identified: 17 out of 20 (85%) in the muscle layer and 3 out of 20 (15%) in the
      submucosa. The three patients in the treatment group showed clinical improvement
      (average clinical score fell from 14 to 2 after 7 days, and remained at 4 after 6
      months of follow-up). The mean pressure of the LES dropped by 29%. Neither
      patient in the placebo group showed clinical improvement, and the mean pressure
      of the LES increased by 35%. Endoscopic 'blind' injection of BT into the LES
      through endoscopy for the management of achalasia is a safe and reproducible
      technique and has a high percentage of exactness.

PMID- 10941860
TI  - Role of oesophageal manometry in clinical practice.
AB  - The present study evaluates the role of oesophageal manometry in clinical
      practice. Over 5 years, 347 consecutive patients were evaluated in our
      oesophageal laboratory. The reasons for referral were: dysphagia (11.5%), gastro
      oesophageal reflux disease (GORD) (46.7%), non-cardiac chest pain (28.5%),
      connective tissue disease (6.9%) and other symptomatology (6.3%). Patients were
      classified into the following five groups according to the referral diagnosis:
      dysphagia (40 patients), gastro-oesophageal reflux disease (GORD) (162 patients),
      non-cardiac chest pain (99 patients), connective tissue disease (24 patients) and
      other symptomatology (22 patients). Abnormalities in oesophageal motility were
      detected in 90% of patients with dysphagia, in 40.1% of patients with GORD, in
      47.5% of subjects with non-cardiac chest pain, in 45.8% of patients with
      connective tissue disease and in 18.2% of subjects with other symptomatology. The
      high prevalence of abnormalities in the dysphagia group was statistically
      significant (p < 0.001), and the range of 95% confidence intervals (0.81-0.99)
      suggests that the value found may be a reasonably good estimate of percentage of
      anomalies detectable in the dysphagia patient population. In the dysphagia group,
      the initial diagnosis was confirmed in 40% of patients and changed in 52.5%; in
      only 7.5% of cases were the manometry results not relevant for determining an
      appropriate diagnosis. Manometry substantially contributed to patients receiving
      the correct treatment in 82.5% of cases (p < 0.001 among all groups). In the GORD
      group and in the non-cardiac chest pain group, the results of manometry were not
      relevant for confirming or changing a diagnosis in 59.8% and 53.5% of cases
      respectively; nevertheless, in both groups, on the basis of manometry results,
      the treatment was changed in 42.5% of patients (p < 0.01 vs. other symptomatology
      group). In conclusion, on the basis of the present data, we can emphasize the
      usefulness of oesophageal manometry assessment in patients with dysphagia or non
      cardiac chest pain, with negative routine examinations, and also in patients with
      refractory GORD who have been considered for antireflux surgery.

PMID- 10941861
TI  - Radionuclide oesophageal transit scintigraphy--a useful method for verification
      of oesophageal dysmotility by cervical vertebropathy.
AB  - We followed up a group of 43 patients suffering from cervical vertebropathy.
      Dynamic scintigraphy revealed a significant prolongation of oesophageal transit
      time of 10 ml of labelled liquid (mean transit time, MTT) in comparison with a
      control group. Patients treated with acupuncture showed a significant reduction
      in MTT in comparison with patients receiving a placebo needle application. The
      group of patients treated with manipulative techniques showed in addition to
      symptom alleviation a significant reduction in MTT. Dynamic scintigraphy
      facilitates verification of oesophageal dysmotility in patients suffering from
      vertebropathy and enables the success of therapy to be readily monitored.

PMID- 10941862
TI  - Esophageal motor disturbances in progressive systemic sclerosis.
AB  - Ten patients with progressive systemic sclerosis (PSS) and esophageal symptoms
      (group 1) and 10 control subjects were studied. Esophageal electromanometry using
      the intermittent pull-through technique and catheter perfusion with distilled
      water were performed in all patients and individuals. The variables studied were
      pressure amplitude in the lower esophageal sphincter (LES) (mmHg) and deglutition
      wave amplitude (mmHg at 5, 10 and 15 cm above LES). In PSS patients, the average
      LES pressure was 18.5 +/- 4.6 mmHg, and in control subjects it was 27 +/- 6.5
      mmHg (p < 0.01). Deglutition wave amplitude at 5, 10 and 15 cm above LES was 13.2
      +/- 7.5 mmHg, 12 +/- 3.7 mmHg and 15 +/- 3.3 mmHg, respectively, in PSS patients.
      In control subjects, it was 67.6 +/- 12.5 mmHg, 58.6 +/- 20.9 mmHg and 52.4 +/-
      21.4 mmHg (p < 0.001). In PSS patients, the pressure amplitude in LES and in the
      body of the esophagus was lower than in control subjects. In PSS patients,
      esophageal manometry showed the absence of normal peristalsis.

PMID- 10941863
TI  - Effect of bombesin on esophageal motility in humans.
AB  - We have investigated the effect of bombesin on esophageal motility and explored
      the mechanism of action of bombesin. Eight healthy subjects were studied in
      random order during intravenous administration of (1) bombesin, (2) bombesin +
      vagal cholinergic receptor blockade with atropine and (3) bombesin +
      somatostatin. Lower esophageal sphincter pressure (LESP) and esophageal body
      motility were recorded continuously by Dent-sleeve manometry. Bombesin
      significantly (p < 0.01) increased LESP from 20 +/- 2 mmHg to 43 +/- 6 mmHg.
      Neither atropine nor somatostatin significantly reduced the bombesin-induced
      increases in LESP. Bombesin significantly (p<0.05) increased peristaltic wave
      amplitude (from 61 +/- 4 to 105 +/- 9 mmHg) and duration (from 2.9 +/- 0.2 to 4.8
      +/- 0.3 s) in the mid and distal part of the esophagus. Neither atropine nor
      somatostatin significantly reduced the esophageal body motor response to
      bombesin. In conclusion (1) bombesin significantly increases LESP and affects
      esophageal body motility by increasing peristaltic wave amplitude and duration
      and (2) the effect of bombesin on esophageal motility is not dependent on vagal
      cholinergic mechanisms and is not mediated by the action of gastrointestinal
      hormones released by bombesin.

PMID- 10941864
TI  - Dietary interference with the use of Bilitec to assess bile reflux.
AB  - The Bilitec probe, which uses bilirubin as a marker for the detection of duodeno
      oesophageal reflux, is subject to interference from strongly coloured foods,
      which can cause erroneously high bilirubin absorbance readings. To overcome this
      problem it is necessary to ingest a diet that is free from such substances. We
      tested the bilirubin absorbance of 32 different food substances in an in vitro
      environment, including many of the foods that are currently recommended for
      consumption during Bilitec studies. 'Dry' foods were blended with water, 'non
      dry' solid foods were blended undiluted, and breakfast cereals were blended with
      milk. Blended mixtures were then tested for bilirubin absorption either undiluted
      or after mixing with hydrochloric acid. The 'absorbance' of weakly coloured foods
      was usually less than the commonly accepted threshold of 0.14, and the
      'absorbance' of strongly coloured foods was usually above this. The 'absorbance'
      of three substances was higher in an acid environment. Three of the currently
      recommended foods had a sufficiently high 'absorbance' to interfere with readings
      in the clinical situation. Of the 32 substances tested, only 13 are suitable when
      the 'absorbance' threshold is set at 0.14. This number can be increased to 19 if
      the threshold is increased to 0.20. From the foods evaluated, enough are suitable
      at the 0.14 threshold to enable a suitable diet to be constructed for most
      patients. Furthermore, many potentially acceptable foods remain untested.
      Clarification of appropriate food substances will help patients to be aware which
      foods are safe to eat, so that food interference can be prevented during Bilitec
      studies.

PMID- 10941865
TI  - Mallory-Weiss syndrome in children.
AB  - The aim of the study was to evaluate the incidence and the etiology of Mallory
      Weiss syndrome in children. The study population comprised 2720 children aged 5
      months to 18 years who had undergone upper gastrointestinal endoscopy. Mallory
      Weiss syndrome was diagnosed in eight (0.3%) of the examined children. Endoscopic
      examination in five of them revealed linear mucosal tears, mostly above and in
      one case also below the gastroesophageal junction. In three children a linear
      scar in the lower portion of the esophagus was seen. No signs of active bleeding
      were revealed in any of the cases. In four children, Mallory-Weiss syndrome was
      accompanied by gastritis and duodenitis; two of these children had Helicobacter
      pylori infection. The concomitant diseases were H. pylori-positive duodenal ulcer
      (1), bronchial asthma and gastroesophageal reflux disease (1), carbon monoxide
      poisoning (1). In one case Mallory-Weiss syndrome was diagnosed in early
      pregnancy. Mallory-Weiss syndrome should be considered, along with others, as a
      cause of acute upper gastrointestinal bleeding in children. There is a great
      variety of etiologic factors in Mallory-Weiss syndrome in children.

PMID- 10941866
TI  - Botulinum toxin for oropharyngeal dysphagia: case report of flexible endoscope
      guided injection.
AB  - Botulinum toxin (BT) has been used in neurology, ophthalmology,
      otorhinolaryngology and gastroenterology. Twenty-four patients with oropharyngeal
      dysphagia treated with BT injection into the cricopharyngeal muscle were
      reported, with good results in up to 79% of the patients. Different techniques
      were used to inject BT: percutaneous (guided by electromyography, computed
      tomography or videofluoroscopy) or direct injection during esophagoscopy (with a
      rigid esophagoscope). We report the first case of oropharyngeal dysphagia treated
      by BT injection into the cricopharyngeal muscle using a flexible scope, with
      clinical, radiological and manometric improvement. A reduction in the disability
      score 4 to 2 and sustained capacity to maintain adequate oral caloric intake were
      observed. The patient was also able to have the tracheotomy orifice closed and
      the gastrostomy tube removed after 3 months. Manometry showed a 38% reduction in
      the upper esophageal sphincter pressure with the presence of pharyngeal waves
      that were previously absent. After 1 year of follow-up, the patient was in good
      condition with mild dysphagia for solid foods. This is another case of complex
      dysphagia and relative hyperfunction of the cricopharyngeal muscle successfully
      treated with BT injection.

PMID- 10941867
TI  - Multiple solitary leiomyomata of the esophagus.
AB  - The present report communicates a case of multiple solitary leiomyomata of the
      esophagus. This is an uncommon condition in which multiple, non-confluent, benign
      esophageal tumors arise in the same patient. The ideal treatment is enucleation
      of the lesions, but when these are--as in the case reported--huge and annular, or
      affect the gastroesophageal junction, resection of the gullet must be performed.

PMID- 10941868
TI  - Smooth muscle tumors of the esophagus: clinicopathological findings in six
      patients.
AB  - Preoperatively, it is difficult to discriminate leiomyoma and leiomyosarcoma of
      the esophagus, which are rare smooth muscle tumors. The objective of this study
      was to evaluate the clinicopathological findings of this unusual lesion. A search
      of the surgery archives of the Toyama Prefectural Central Hospital of Pathology
      revealed six cases of esophageal smooth muscle tumors. Clinicopathological
      findings were reviewed retrospectively. Only three patients (50%) presented with
      dysphagia, and the remaining three patients were asymptomatic. These patients
      underwent surgical excision. Histologically four of the six tumors were
      leiomyomas, and the other two tumors were leiomyosarcomas. Two tumors were in the
      upper to middle esophagus, and the remaining four were in the distal esophagus.
      On endoscopic examination, all tumors were noted to be polypoid. The two
      leiomyosarcomas measured over 5 cm and the four leiomyomas less than 4 cm.
      Neither ulceration nor necrosis proved to be of use in discriminating leiomyoma
      and leiomyosarcoma. The two patients with leiomyosarcoma died of liver metastasis
      10 and 22 months after the treatment. Patients with leiomyosarcoma presented with
      distant metastasis and/or recurrence, with hematogeneous metastasis being the
      predominant type of recurrence.

PMID- 10941869
TI  - Symptomatic mediastinal lymphatic cyst after esophagectomy.

PMID- 10941870
TI  - Diversity of mouse lipoxygenases: identification of a subfamily of epidermal
      isozymes exhibiting a differentiation-dependent mRNA expression pattern.
AB  - By using reverse transcription-polymerase chain reaction technology (RT-PCR) and
      Northern blot analysis, the tissue-specific mRNA expression patterns of seven
      mouse lipoxygenases (LOX)--including 5S-, 8S-, three isoforms of 12S-, 12R-LOX,
      and a LOX of an as-of-yet unknown specificity, epidermis-type LOX-3 (e-LOX-3)-
      were investigated in NMRI mice. Among the various tissues tested epidermis and
      forestomach were found to express the broadest spectrum of LOX. With the
      exception of 5S- and platelet-type 12S-LOX (p12S-LOX) the remaining LOX showed a
      preference to exclusive expression in stratifying epithelia of the mouse, in
      particular the integumental epidermis. The expression of the individual LOX in
      mouse epidermis was found to depend on the state of terminal differentiation of
      the keratinocytes. mRNA of epidermis-type 12S-LOX (e12S-LOX) was detected in all
      layers of neonatal and adult NMRI mouse skin, whereas expression of p12S-LOX, 12R
      LOX, and e-LOX-3 was restricted to suprabasal epidermal layers of neonatal and
      adult mice. 8S-LOX mRNA showed a body-site-dependent expression in that it was
      detected in stratifying epithelia of footsole and forestomach but not in back
      skin epidermis. In the latter, 8S-LOX mRNA was strongly induced upon treatment
      with phorbol esters. With the exception of e12S-LOX and p12S-LOX, the isozymes
      that are preferentially expressed in stratifying epithelia are structurally
      related and may be grouped together into a distinct subgroup of epidermis-type
      LOX.

PMID- 10941871
TI  - Purification, molecular cloning, and expression of the gene encoding fatty acid
      13-hydroperoxide lyase from guava fruit (Psidium guajava).
AB  - Guava fruit was identified as a particularly rich source of 13-hydroperoxide
      lyase activity. The enzyme proved stable to chromatographic procedures and was
      purified to homogeneity. Based on gel filtration and gel electrophoresis, the
      native enzyme appears to be a homotetramer with subunits of 55 kD. Starting with
      primers based on the peptide sequence, the enzyme was cloned by polymerase chain
      reaction with 3' and 5' rapid amplification of cDNA ends. The sequence shows
      approximately 60-70% identity to known 13-hydroperoxide lyases and is classified
      in cytochrome P450 74B subfamily as CYP74B5. The cDNA was expressed in
      Escherichia coli (BL21 cells), with optimal enzyme activity obtained in the
      absence of isopropyl-beta-D-thiogalactopyranoside and delta-aminolevulinic acid.
      The expressed enzyme metabolized 13(S)-hydroperoxylinolenic acid over 10-fold
      faster than 13(S)-hydroperoxylinoleic acid and the 9-hydroperoxides of linoleic
      and linolenic acids. 13(S)-Hydroperoxylinolenic acid was converted to 12-oxododec
      9(Z)-enoic acid and 3(Z)-hexenal, as identified by gas chromatography-mass
      spectrometry. The turnover number with this substrate, with enzyme concentration
      estimated from the Soret absorbance, was approximately 2000/s, comparable to
      values reported for the related allene oxide synthases. Distinctive features of
      the guava 13-hydroperoxide lyase and related cytochrome P450 are discussed.

PMID- 10941872
TI  - Gastroprotection of DNA with a synthetic cholic acid analog.
AB  - The oral delivery of functional DNA to the gastrointestinal system would
      constitute a desirable, noninvasive method for potentially treating a variety of
      diseases. The digestive process, however, remains a formidable barrier. This
      dilemma may be addressed by using targeted liposomes both to protect the
      polynucleotide and to deliver the therapeutic DNA with high tissue specificity.
      The present study represents the initial steps toward developing a novel gene
      delivery system designed to interact with the enterohepatic receptors of the
      small intestine. Two cholic acid esters were synthetically modified at position
      C(3) to incorporate a DNA-binding domain. These novel compounds were evaluated
      for their ability to protect DNA from the nucleases found in gastrointestinal
      segments. Additionally, the compounds were screened as a component of a gene
      delivery vector. Formulations containing the new bile salt derivatives protected
      DNA from degradation for more than 2 h and were capable of transfecting cultured
      NIH 3T3 cells.

PMID- 10941874
TI  - Do glycerolipids display lateral heterogeneity in the thylakoid membrane?
AB  - The lateral heterogeneity of lipids in the thylakoid membrane has been questioned
      for over 20 yrs. It is generally believed that glycerolipids are asymmetrically
      distributed within the plane of the membrane. In the present investigation, we
      isolated several thylakoid membrane domains by using sonication followed by
      separation in an aqueous dextran-polyethylene glycol two-phase system. This
      technique, which avoids detergent treatments, allowed us to obtain stroma and
      grana lamellae vesicles as well as grana central core and grana margin vesicles
      from thylakoids. The relative distribution of the four lipid classes, i.e.,
      monogalactosyldiacylglycerol, digalactosyldiacylglycerol,
      sulfoquinovosyldiacylglycerol, and phosphatidylglycerol, was found to be
      statistically identical in all four thylakoid fractions and in whole thylakoids.
      Similarly, the relative amount of fatty acids in each individual lipid and the
      eight main phosphatidylglycerol molecular species was identical in all thylakoid
      membrane fractions tested as well as in the intact thylakoid membrane. Based on
      presently available procedures for obtaining thylakoid subfractions that are
      unable to discriminate microdomains within the membrane, it is concluded that
      glycerolipids are evenly distributed within the plane of the thylakoid membrane.
      These data are discussed in terms of "bulk" and "specific" lipids.

PMID- 10941873
TI  - Liver and intestinal fatty acid-binding protein expression increases phospholipid
      content and alters phospholipid fatty acid composition in L-cell fibroblasts.
AB  - Although fatty acid-binding proteins (FABP) differentially affect fatty acid
      uptake, nothing is known regarding their role(s) in determining cellular
      phospholipid levels and phospholipid fatty acid composition. The effects of liver
      (L)- and intestinal (I)-FABP expression on these parameters were determined using
      stably transfected L-cells. Expression of L- and I-FABP increased cellular total
      phospholipid mass (nmol/mg protein) 1.7- and 1.3-fold relative to controls,
      respectively. L-FABP expression increased the masses of choline
      glycerophospholipids (ChoGpl) 1.5-fold, phosphatidylserine (PtdSer) 5.6-fold,
      ethanolamine glycerophospholipids 1.4-fold, sphingomyelin 1.7-fold, and
      phosphatidylinositol 2.6-fold. In contrast, I-FABP expression only increased the
      masses of ChoGpl and PtdSer, 1.2- and 3.1-fold, respectively. Surprisingly, both
      L- and I-FABP expression increased ethanolamine plasmalogen mass 1.6- and 1.1
      fold, respectively, while choline plasmalogen mass was increased 2.3- and 1.7
      fold, respectively. The increase in phospholipid levels resulted in dramatic 48
      and 33% decreases in the cholesterol-to-phospholipid ratio in L- and I-FABP
      expressing cells, respectively. L-FABP expression generally increased
      polyunsaturated fatty acids, primarily by increasing 20:4n-6 and 22:6n-3, while
      decreasing 18:1n-9 and 16:1n-7. I-FABP expression generally increased only 20:4n
      6 proportions. Hence, expression of both I- and L-FABP differentially affected
      phospholipid mass, class composition, and acyl chain composition. Although both
      proteins enhanced phospholipid synthesis, the effect of L-FABP was much greater,
      consistent with previous work suggesting that these two FABP differentially
      affect lipid metabolism.

PMID- 10941875
TI  - Dietary n-3 long-chain polyunsaturated fatty acid deprivation, tissue lipid
      composition, ex vivo prostaglandin production, and stress tolerance in juvenile
      Dover sole (Solea solea L.).
AB  - Larval Dover sole fed an Artemia diet supplemented with n-3 long-chain (C20 +
      C22) polyunsaturated fatty acids (PUFA) are known to be more resistant to low
      temperature injury. Here we explore the relationship between tissue fatty acid
      composition and tolerance of stressful environmental conditions over the larval
      and early juvenile periods. Artemia nauplii supplemented with n-3 long-chain PUFA
      deficient and PUFA-enriched oil emulsions were fed to two groups of larvae. Whole
      body tissue samples from the resulting PUFA-deficient and -enriched juveniles
      possessed 12.1 and 21.9% n-3 long-chain PUFA, respectively. These differences
      were at the expense of C18 PUFA, while proportions of saturated fatty acids,
      monounsaturated fatty acids, and total PUFA were unaffected. Brain and eye
      tissues from the PUFA-deficient fish contained lower levels of 22:6n-3, known to
      be important for optimal nervous system function, incorporating instead a range
      of fatty acids of lower unsaturation. PUFA-deprived juveniles showed
      substantially greater mortality when exposed to a combination of low temperature
      and low salinity, as well as to high temperature and to hypoxia. After adaptation
      to the different diets, both dietary groups were fed a common formulated feed
      high in n-3 long-chain PUFA. Tissue PUFA in both groups progressively increased
      to the same high value, with a consequent loss of the differences in cold
      susceptibility. These correlated changes support a link between dietary
      manipulation of n-3 long-chain PUFA and development of a stress-sensitive
      phenotype. PUFA deprivation had no detectable effect upon static hydrocarbon
      order of purified brain membranes (as assessed by fluorescence polarization) but
      was associated with an increase in the whole-body content of prostaglandins. We
      conclude that susceptibility to environmental stress is responsive to dietary n-3
      long-chain PUFA manipulation, possibly due to altered tissue development or the
      overproduction of eicosanoids.

PMID- 10941876
TI  - Long-term feeding of dietary oils alters lipid metabolism, lipid peroxidation,
      and antioxidant enzyme activities in a teleost (Anabas testudineus Bloch).
AB  - Anabas testudineus (climbing perch), average body weight 21+/-1 g, were
      maintained in culture tanks and fed a 35% protein feed plus an additional
      supplementation of three dietary oils (20% each of coconut oil, palm oil, or cod
      liver oil). Body weight gain was similar among all groups. However, several
      hepatic lipogenic enzymes such as malic enzyme (ME), NADP-isocitrate
      dehydrogenase (ICDH), glucose 6-phosphate dehydrogenase (G6PDH), 6
      phosphogluconate dehydrogenase (6PGDH) and beta-hydroxy-1-methyl glutaryl CoA
      reductase (HMG CoA reductase) were assayed, and they responded differently.
      Hepatic ME and G6PDH activities showed a significant decrease in the coconut oil
      and palm oil groups, but there was no significant change in ICDH activity. The
      6PGDH activities were reduced, whereas HMG CoA reductase activity was increased
      in the palm oil-treated group. Cholesterol synthesis in the liver and muscle
      increased in the palm oil-treated group, but liver phospholipids did not show any
      significant change in fish supplemented with oils rich in saturated fatty acids.
      Triacylglycerol and free fatty acid concentrations were high in the coconut oil-
      and palm oil-supplemented groups. Lipid peroxidation products such as
      thiobarbituric acid-reactive substances and conjugated dienes decreased in the
      same two groups. Antioxidant potential was high in all groups as evidenced by
      increased activity of superoxide dismutase, glutathione peroxidase, and
      glutathione content. The results of this study indicate that in fish, dietary
      lipids depress hepatic lipogenic activity as well as lipid peroxidation products
      by maintaining high levels of antioxidant enzymes.

PMID- 10941877
TI  - Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid
      composition and function.
AB  - Although essential to host defense, neutrophils are also involved in numerous
      inflammatory disorders including rheumatoid arthritis. Dietary supplementation
      with relatively large amounts of fish oil [containing >2.6 g eicosapentaenoic
      acid (EPA) plus 1.4 g docosahexaenoic acid (DHA) per day] can attenuate
      neutrophil functions such as chemotaxis and superoxide radical production. In
      this study, the effects of more moderate supplementation with fish oil on
      neutrophil lipid composition and function were investigated. The rationale for
      using lower supplementary doses of fish oil was to avoid adverse gastrointestinal
      problems, which have been observed at high supplementary concentrations of fish
      oil. Healthy male volunteers aged <40 yr were randomly assigned to consume one of
      six dietary supplements daily for 12 wk (n = 8 per treatment group). The dietary
      supplements included four different concentrations of fish oil (the most
      concentrated fish oil provided 0.58 g EPA plus 1.67 g DHA per day), linseed oil,
      and a placebo oil. The percentages of EPA and DHA increased (both P < 0.05) in
      neutrophil phospholipids in a dose-dependent manner after 4 wk of supplementation
      with the three most concentrated fish oil supplements. No further increases in
      EPA or DHA levels were observed after 4 wk. The percentage of arachidonic acid in
      neutrophil phospholipids decreased (P < 0.05) after 12 wk supplementation with
      the linseed oil supplement or the two most concentrated fish oil supplements.
      There were no significant changes in N-formyl-met-leu-phe-induced chemotaxis and
      superoxide radical production following the dietary supplementations. In
      conclusion, low-to-moderate amounts of dietary fish oil can be used to manipulate
      neutrophil fatty acid composition. However, this may not be accompanied by
      modulation of neutrophil functions such as chemotaxis and superoxide radical
      production.

PMID- 10941878
TI  - Preferential loss of visceral fat following aerobic exercise, measured by
      magnetic resonance imaging.
AB  - The aim of this study was to use whole-body magnetic resonance imaging (MRI)
      together with biochemical and anthropometric measurements to study the influence
      of regular moderate exercise with no dietary intervention on adipose tissue
      distribution in nonobese healthy women. We found significant decreases in both
      total (28.86+/-2.24 vs. 27.00+/-2.27 liters, P < 0.05) and regional fat depots
      (visceral fat: 1.68+/-0.21 vs. 1.26+/-0.18 liters, P < 0.01) using whole-body MRI
      despite no significant change in body weight, body mass index, or the waist-to
      hip ratio. Interestingly, no changes in body fat content were found using
      anthropometry or impedance. There was a significant increase in high density
      lipoprotein cholesterol (1.58+/-0.06 vs. 1.66+/-0.08 mmol/L P < 0.02) following
      exercise although there were no changes in other blood lipids such as
      triglycerides. In summary, moderate aerobic exercise over a period of 6 mon
      resulted in a preferential loss in visceral fat in nonobese healthy women, and
      this may help to explain some of the health benefits associated with regular and
      moderate physical activity.

PMID- 10941879
TI  - Conjugated linoleic acid supplementation in humans: effects on body composition
      and energy expenditure.
AB  - Recent animal studies have demonstrated that dietary conjugated linoleic acid
      (CLA) reduces body fat and that this decrease may be due to a change in energy
      expenditure. The present study examined the effect of CLA supplementation on body
      composition and energy expenditure in healthy, adult women. Seventeen women were
      fed either a CLA capsule (3 g/d) or a sunflower oil placebo for 64 d following a
      baseline period of 30 d. The subjects were confined to a metabolic suite for the
      entire 94 d study where diet and activity were controlled and held constant.
      Change in fat-free mass, fat mass, and percentage body fat were unaffected by CLA
      supplementation (0.18+/-0.43 vs. 0.09+/-0.35 kg; 0.01+/-0.64 vs. -0.19+/-0.53 kg;
      0.05+/-0.62 vs. -0.67+/-0.51%, placebo vs. CLA, respectively). Likewise, body
      weight was not significantly different in the placebo vs. the CLA group (0.48+/
      0.55 vs. -0.24+/-0.46 kg change). Energy expenditure (kcal/min), fat oxidation,
      and respiratory exchange ratio were measured once during the baseline period and
      during weeks 4 and 8 of the intervention period. At all three times, measurements
      were taken while resting and walking. CLA had no significant effect on energy
      expenditure, fat oxidation, or respiratory exchange ratio at rest or during
      exercise. When dietary intake was controlled, 64 d of CLA supplementation at 3
      g/d had no significant effect on body composition or energy expenditure in adult
      women, which contrasts with previous findings in animals.

PMID- 10941880
TI  - Conjugated linoleic acid supplementation in humans: effects on circulating leptin
      concentrations and appetite.
AB  - Conjugated linoleic acid (CLA) has been demonstrated to reduce body fat in
      animals. However, the mechanism by which this reduction occurs is unknown. Leptin
      may mediate the effect of CLA to decrease body fat. We assessed the effects of 64
      d of CLA supplementation (3 g/d) on circulating leptin, insulin, glucose, and
      lactate concentrations in healthy women. Appetite was assessed as a physiological
      correlate of changes in circulating leptin levels. Analysis of plasma leptin
      concentrations adjusted for adiposity by using fat mass as a covariate showed
      that CLA supplementation significantly decreased circulating leptin
      concentrations in the absence of any changes of fat mass. Mean leptin levels
      decreased over the first 7 wk and then returned to baseline levels over the last
      2 wk of the study in the CLA-treated group. Appetite parameters measured at
      around the time when the greatest decreases in leptin levels were observed showed
      no significant differences between supplementation and baseline determinations in
      the CLA-supplemented group or between the CLA and placebo-supplemented groups.
      There was a nonsignificant trend for mean insulin levels to increase toward the
      end of the supplementation period in CLA-treated subjects. CLA did not affect
      plasma glucose and lactate over the treatment period. Thus, 64 d of CLA
      supplementation in women produced a transient decrease in leptin levels but did
      not alter appetite. CLA did not affect these parameters in a manner that promoted
      decreases of adiposity.

PMID- 10941881
TI  - Determination of the conjugated linoleic acid-containing triacylglycerols in New
      Zealand bovine milk fat.
AB  - Reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet
      (UV) detection at 233 nm was used to separate, quantify, and identify the
      triacylglycerols (TAG) of milk fat that contain conjugated linoleic acid (CLA).
      The absorbance at 233 nm was substantially due to CLA-TAG (chromatography of some
      representative TAG devoid of CLA, such as tripalmitin and triolein, showed poor
      responses at 233 nm, 1/800th that of CLA-TAG). A CLA molar extinction coefficient
      at 233 nm of 23,360 L mol(-1) cm(-1) and an HPLC UV response factor were obtained
      from a commercially available cis-9,trans-11-CLA standard. This molar extinction
      coefficient was only 86% of reported literature values. Summation of all
      chromatographic peaks absorbing at 233 nm using the corrected response factor
      gave good agreement with independent determinations of total CLA by gas
      chromatography and UV spectrophotometry. This agreement allowed quantification of
      individual CLA-TAG peaks in the HPLC separation of a typical New Zealand bovine
      milk fat. Three CLA-containing TAG, CLA-dipalmitin, CLA-oleoyl-palmitin and CLA
      diolein, were prepared by interesterification of tripalmitin with the respective
      fatty acid methyl esters and used to assign individual peaks in the reversed
      phase chromatography of total milk fat, of which CLA-oleoyl-palmitin was
      coincident with the largest UV peak. Band fractions from argentation thin-layer
      chromatography of total milk fat were similarly employed to identify five
      predominant CLA-TAG groups in total milk fat: CLA-disaturates, CLA-oleoyl
      saturates, CLA-vaccenyl-saturates, CLA-vaccenyl-olein, and CLA-diolein.

PMID- 10941882
TI  - Gas chromatography-high resolution selected-ion mass spectrometric identification
      of trace 21:0 and 20:2 fatty acids eluting with conjugated linoleic acid isomers.
AB  - High-resolution selected-ion recording (SIR) of the exact molecular ion mass was
      used to confirm unambiguously the presence of conjugated linoleic acid (CLA)
      derivatives in biological matrices and standard mixtures and to differentiate non
      CLA derivatives from CLA derivatives in the CLA region of the gas chromatogram.
      The success of this method was based on the selectivity of the SIR technique and
      its sensitivity, which was comparable to that of flame-ionization detection. A
      minor fatty acid methyl ester (FAME) was identified as methyl heneicosanoate
      (21:0), and six isomers of 20:2 FAME were found to elute in the CLA region.
      Isomerization of a standard CLA mixture resulted in a non-CLA flame-ionization
      response eluting in the CLA region of the gas chromatogram. It is therefore
      recommended that the identification of minor CLA isomers in natural products or
      biological matrices should include their direct confirmation by mass
      spectrometry.

PMID- 10941883
TI  - A comparison of lycopene and astaxanthin absorption from corn oil and olive oil
      emulsions.
AB  - The effect of different oils on the absorption of carotenoids was investigated in
      mesenteric lymph duct cannulated rats. Sixteen treatment emulsions containing
      increasing concentrations of either lycopene (LYC) or astaxanthin (AST) (5, 10,
      15, 20 micromol/L) were prepared with olive oil or corn oil and continuously
      infused into the duodenum of the rat. Absorption of carotenoids into the
      mesenteric lymph duct was determined. Absorption of LYC and AST from both oils
      increased with the amount infused into the duodenum. The average recovery of AST
      in the lymph from the olive oil emulsion was 20% but was decreased to 13% from
      emulsions containing corn oil. Lycopene was not as well absorbed as AST. The
      average recovery of LYC was 6% from olive oil emulsions but only 2.5% when
      infused with corn oil. The LYC used in this study was isolated from tomato paste
      and was primarily in the all-trans form. We did not observe any significant
      isomerization of all-trans LYC to 9-cis LYC during absorption. We conclude that
      the type of oil with which a carotenoid is consumed can influence its absorption.

PMID- 10941884
TI  - Cervical pedicle screw insertion: assessment of safety and accuracy with computer
      assisted image guidance.

PMID- 10941885
TI  - Prospective functional evaluation of the surgical treatment of neurogenic
      claudication in patients with lumbar spinal stenosis.
AB  - A prospective evaluation of patients with lumbar spinal stenosis undergoing
      operative treatment was performed using treadmill-bicycle functional testing as
      well as Oswestry and Visual Analog Pain scales for self-assessment. Thirty-two
      patients undergoing spinal stenosis decompression with and without a concomitant
      spinal fusion were prospectively evaluated, preoperatively and a minimum of 2
      years postoperatively. Surgical treatment was demonstrated to produce significant
      improvement in walking ability, and to a lesser degree, in the ability to bicycle
      2 years postoperatively. Improvement in patient function demonstrated on the
      Oswestry questionnaire correlated with decreased pain observed on the Visual
      Analog Pain scale. The treadmill-bicycle test appears to be a useful tool for the
      differential diagnosis of neurogenic claudication and may be used as an objective
      test of postoperative outcome.

PMID- 10941886
TI  - The usefulness of electrical stimulation for assessing pedicle screw placements.
AB  - The purpose of this study was to further establish the efficacy of pedicle screw
      stimulation as a monitoring technique to avoid nerve root injury during screw
      placement. The study population consisted of 662 patients in whom 3,409 pedicle
      screws were placed and tested by electrical stimulation. If stimulation resulted
      in a myogenic response at a stimulation intensity of 10 mA or less, the placement
      of the screw was inspected. Inspection was necessary for 3.9% of the screw
      placements in 15.4% of the study population. None of the patients in the study
      experienced any new postoperative neurologic deficits. These findings provide
      guidelines for the interpretation of stimulation data and support the use of this
      technique as an easy, inexpensive, and quick method to reliably assess screw
      placements and protecting neurological function.

PMID- 10941887
TI  - Prospective comparison of the effect of direct current electrical stimulation and
      pulsed electromagnetic fields on instrumented posterolateral lumbar arthrodesis.
AB  - The purpose of this prospective study was to compare the effect of adjunctive
      direct current (DC) electrical stimulation and pulsed electromagnetic field
      therapy (PEMF) on augmentation of instrumented lumbar fusion. Sixty-one patients
      undergoing lumbar spine fusion were enrolled in the study and randomized to one
      of three treatment protocols: 1) adjunctive PEMF group (n = 22) fitted with
      Spinal-Stim model 8212(AME) within 30 days of surgery; 2) DC group (n = 17) had a
      SpF-2T stimulator(EBI) implanted at the time of surgery; or 3) control group (n =
      22). The fusion mass bone mineral density (BMD) assessment was performed on 3
      month and 1-year radiographs for each patient. Lateral flexion-extension and
      anteroposterior radiographs were evaluated at 1 year to determine the presence of
      fusion. Clinical outcome patient analyses were performed at 1 year. At 1-year
      follow-up, radiographic fusion and fusion mass bone density were not
      significantly different among the groups. In the nonstimulated group, there were
      43% excellent, 43% good, and 14% fair results. In the PEMF group, there were 35%
      excellent, 50% good, 10% fair, and 5% poor results. In the DC group, there were
      32% excellent, 37% good, and 31% fair results. The results of the current study
      suggest that electrical stimulation does not significantly enhance fusion rate in
      instrumented lumbar arthrodesis, although we observed a statistically
      insignificant trend toward increased fusion mass BMD in the electrically
      stimulated groups. The significance of increased BMD remains unknown.

PMID- 10941889
TI  - Is there a need for lumbar orthosis in mild compression fractures of the
      thoracolumbar spine?: A retrospective study comparing the radiographic results
      between early ambulation with and without lumbar orthosis.
AB  - Compression fractures of the thoracolumbar spine are common in spinal trauma.
      Most patients are treated with early ambulation. Bracing is an option not always
      recommended by the treating team. There are no definite recommendations so far
      regarding the need for lumbar orthosis in this type of injury. The authors
      retrospectively compared two methods for treating patients with compression as
      great as 30%: early ambulation with and without lumbar orthosis. The results show
      that although demographic variables, type of injury, and cause of injury were
      similar between the groups, neither treatment emerged as superior. Thoracolumbar
      fractures with compression as much as 30% can be treated with early ambulation
      and no external support. Close clinical and radiographic follow-up is essential.

PMID- 10941888
TI  - Injuries of the thoracolumbar spine associated with restraint use in head-on
      motor vehicle accidents.
AB  - Many authors have described spinal and bodily injuries associated with seat belt
      use. However, most reports have focused primarily on lap seat belts and resultant
      flexion-distraction injuries. This retrospective chart review studies the
      relation between the specific type of restraint or air bag and the resultant
      thoracolumbar spinal injury subtype and associated bodily injuries. The charts of
      221 patients who had sustained thoracolumbar fractures in motor vehicle accidents
      during a 10-year period were reviewed, and 37 patients were identified whose
      accidents were clearly described as a frontal collision and whose specific form
      of restraint was recorded. Among the 15 patients who used a shoulder strap and
      lap belt device (three-point restraint), 12 patients sustained burst fractures
      (80%) compared with 4 of the 14 patients (28.6%) restrained with lap seat belts
      alone. Life-threatening intraabdominal injuries occurred in 57.1% of lap-belted
      victims and in 26.7% of patients who used three-point restraints, and the
      character of these injuries also differed. No patients in an automobile in which
      an air bag deployed sustained major associated bodily injuries. Among restrained
      occupants of head-on motor vehicle accidents who have sustained a thoracolumbar
      fracture, patients using lap belts are more likely to sustain the classic flexion
      distraction injury patterns, whereas patients using three-point restraints may
      sustain a higher incidence of burst fractures. In addition, three-point
      restraints are associated with a decreased risk of intraabdominal injury compared
      with lap seat belts.

PMID- 10941890
TI  - Iatrogenic lumbar spondylolisthesis: treatment by anterior fibular and iliac
      arthrodesis.
AB  - A retrospective independent radiographic and chart review was undertaken for 17
      patients who underwent a unique anterior salvage procedure for iatrogenic and
      progressive postoperative spondylolisthesis. This one-stage anterior
      transabdominal discectomy, reduction, stabilization, and arthrodesis was first
      performed in 1979. Of the 17 patients, all complained of leg pain, 14 of back
      pain, 11 had neurogenic claudication, and 2 were bedridden preoperatively because
      of their pain. Of the 17 patients, 7 had no neurologic deficits, 2 had cauda
      equina syndrome, and the remaining 8 had motor root deficits. The average number
      of posterior operations before our salvage procedure was 1.8, with a range of 1
      to 3. Eight patients had an average of 1.6 attempts at posterior arthrodesis,
      with a range of 1 to 3 procedures. Two patients had a grade I spondylolisthesis,
      11 a grade II, and 4 a grade III. Follow-up was available for 16 patients from 2
      years and 3 months to 11 years and 5 months after the index operation (mean, 6
      years and 5 months). One patient with severe cardiovascular disease died
      perioperatively. This anterior procedure was able to restore spinal stability and
      decompress the neural elements in 13 of 16 patients. Eleven obtained a solid
      arthrodesis. Three patients required further spinal surgery: two posterior
      fusions for symptomatic nonunions and one posterior foraminotomy for persistent
      foraminal stenosis. No patient deteriorated neurologically, the two with cauda
      equina syndrome recovered, and all but one patient with motor root deficits
      recovered fully. At latest follow-up, there were six excellent, seven good, and
      three fair results. There were no poor results. Although technically difficult
      and troubled by complications, the relative historical merits and principles of
      this unique anterior salvage procedure probably warrant further consideration,
      especially in light of evolving anterior surgical technologies.

PMID- 10941891
TI  - Adult tethered cord syndrome.
AB  - Although often overlooked, the diagnosis of adult "tethered cord syndrome" (TCS)
      is important because the manifestations of this syndrome are readily reversible
      by untethering. Too often, adult patients with TCS are misdiagnosed as having
      "failed back syndrome" or other unrelated spinal problems. As a result, many
      patients are treated with modalities which fail to improve neurological function.
      The aims of this review are to acquaint readers with the pathophysiology,
      symptomatology, diagnosis, and treatment of adult TCS based on author's
      experience in 70 cases. Adult TCS manifested by severe back and leg pain, a
      subtle onset of motor/sensory changes and musculoskeletal deformities is
      correlated to TCS pathophysiology and imaging studies. Timely diagnosis of TCS
      can lead to pain relief and restoration of neurologic function and patient
      gratification.

PMID- 10941892
TI  - The management of one-level anterior cervical corpectomy with fusion using
      Atlantis hybrid plates: preliminary experience.
AB  - To limit high pseudarthrosis rates encountered after cervical procedures for
      adjacent two-level disease, one-level anterior corpectomy with fusion was
      performed using the newly available Atlantis hybrid plates (fixed screws placed
      superiorly and variable screws placed inferiorly). Eight one-level anterior
      corpectomies with fusion were performed using iliac autografts and Atlantis
      hybrid plates. Nurick and Medical Outcomes Trust Short Form 36 scores were
      recorded before operation (Nurick grade 2.3) and 6 months after operation. Fusion
      status was followed an average of 9 months (range, 8 to 11 months). Fusion was
      confirmed an average of 6 months after operation in seven patients, when the mean
      Nurick grade was 0.2 and all had improved on the eight Medical Outcomes Trust
      Short Form 36 health scales. Atlantis plates contributed to successful fusion in
      seven of eight patients undergoing one-level anterior corpectomy with fusion
      using Atlantis hybrid plates.

PMID- 10941893
TI  - Results of cervical laminoplasty and a comparison between single and double trap
      door techniques.
AB  - Thirty-seven patients were studied for an average of 32.1 months after canal
      expansive laminoplasty for the treatment of multiple-level cervical stenosis
      caused by spondylosis, ossification of posterior longitudinal ligament, prolapsed
      intervertebral disc, and other conditions. Short-term and medium-term results
      were recorded clinically, using the scoring system proposed by the Japanese
      Orthopedic Association. The canal expansion was also recorded with radiological
      studies. The improvement rate was good to excellent in 58.3% of the patients.
      Postoperative neurological deterioration occurred in only four patients. Poorer
      results were observed in female patients and in those in whom surgery was
      delayed. Surgery within 12 months of onset of symptoms gave good results. Serious
      complications occurred in only two patients. There were 12 patients who were
      treated with the single trap-door (unilateral) laminoplasty and 25 patients
      treated with the double trap-door (sagittal splitting of the spinous processes)
      laminoplasty; their results were compared. There was no significant difference in
      neurological outcome between the two methods.

PMID- 10941894
TI  - Biomechanical evaluation of occipital fixation.
AB  - Many studies have shown a positive correlation among screw pullout strength,
      screw insertional torque, bone thickness, and areal bone mineral density (BMD)
      measured by dual-energy X-ray absorptiometry. Variations are significant in the
      anatomy of the occipital bone. But no studies have correlated these variables
      with respect to the two locations commonly used for plate fixation to the
      occiput. The purpose of this study was to determine the thickness and quality of
      the occipital bone and to correlate these variables with the insertional torque
      of screws and the pullout strength of plates secured into two different locations
      on the occiput. The occiputs of 12 adult human fresh frozen cadaveric specimens
      were used. The specimens were analyzed by dual-energy X-ray absorptiometry.
      Direct thickness measurements of the occiput were performed. Areal and volumetric
      BMD were measured. A simple pelvic reconstruction plate (3.2 mm) was fixed to the
      occiput either laterally or at the midline with bicortical 4-mm cancellous
      screws. Torque was recorded at the time of insertion of each screw. Axial pullout
      tests were performed on all specimens. The peak load, failure load, stiffness,
      and energy to failure were recorded for each construct. Statistical analysis
      showed that the average thickness of occipital bone is greater in the midline
      than laterally. Occipital bone is thicker and screw torque is greater close to
      the inion. There is a positive correlation between bone thickness, areal BMD as
      measured by dual-energy X-ray absorptiometry, screw insertional torque, and
      strength of fixation. A plate fixed in the midline region of the occiput provides
      more rigid fixation than a plate fixed laterally. Areal BMD correlates better
      than volumetric BMD with bone thickness and is a reliable predictor of the
      strength of occipital fixation.

PMID- 10941895
TI  - Neck pain secondary to radiculopathy of the fourth cervical root: an analysis of
      12 surgically treated patients.
AB  - Neck pain can originate from any number of factors. Perhaps the most difficult
      symptom complex to resolve is axial neck pain arising from upper cervical nerve
      root compression. The purpose of this study is to report the results of surgical
      intervention in a series of patients with neck pain from C4 radiculopathy. Twelve
      consecutive patients who were diagnosed with C4 radiculopathy were
      retrospectively reviewed (follow-up, 22+/-16.3 months). Patients underwent either
      anterior cervical discectomy and fusion or posterior laminoforaminotomy at the C3
      C4 segment. The results show that a good to excellent clinical result can be
      achieved in most patients (92% in our series). The importance of identifying
      patients with C4 radiculopathy lies in the fact that surgery can alter the
      natural history of neck pain secondary to upper cervical root radiculopathy,
      unlike axial neck pain from degenerative disk disease.

PMID- 10941896
TI  - A plate-rod device for treatment of cervicothoracic disorders: comparison of
      mechanical testing with established cervical spine in vitro load testing data.
AB  - Posterior cervical internal fixation has long been accomplished using wires,
      hooks, and rods. More recently, the cervical lateral mass screw and plate or rod
      systems have been used effectively in unstable lower cervical spine disorders.
      Each form of fixation has its advantages and disadvantages. Interspinous wiring
      and lateral mass screw placement obviate canal penetration in the cervical region
      but are associated with a potential neurologic risk as a result of canal
      encroachment. Minor canal intrusion by laminar hooks in the thoracic spine pose a
      lesser neurologic risk than in the cervical region. To exploit the benefits and
      safety features of spinal instrumentation, a combination plate rod construct
      (PRC) has been developed that obviates canal penetration in the cervical region
      by way of lateral mass and cervical pedicle screw fixation and hooks or wires in
      the thoracic spine. A biomechanical analysis of the PRC device was performed and
      compared with the in vivo maximal load data of the cervical spine and established
      maximal load data of the Roy-Camille posterior cervical fixation system. The PRC
      has greater strength and resistance to failure than is necessary to sustain
      maximal in vivo cervical spine loads, and it has also compared favorably with the
      parameters of the Roy-Camille system. The PRC device, or variations on it, is an
      excellent option for spinal fixation across the cervicothoracic junction because
      of its superior biomechanical qualities and versatility in stabilizing a complex
      anatomic junction of the spine.

PMID- 10941897
TI  - Isolated posterior column dysfunction: an unusual presentation of spondylotic
      myelopathy.
AB  - Two patients with previously unreported clinically evident myelopathy caused by
      herniated intervertebral disks are described. These patients had isolated
      posterior column dysfunction in the lower extremities without motor deficits,
      abnormal reflexes, spinothalamic sensory abnormalities, or sphincter changes. The
      level of cord compression was significantly more cranial than suggested by
      clinical localization, and the results of initial radiographic studies were
      unremarkable. Study of posterior column dysfunction using somatosensory evoked
      potentials was helpful in localizing the lesions and guiding appropriate
      neuroradiologic studies.

PMID- 10941898
TI  - Primary bone tumors of the femur presenting with spinal symptoms: a report of two
      cases and review of the literature.
AB  - Two case reports of femoral bone lesions simulating lumbar spinal disease are
      presented. Physical examination and case history were strongly suggestive of
      lumbar spinal pathology. In case 1, surgical resection of a venous hemangioma in
      the lumbar epidural space was performed but did not relieve pain. In case 2,
      conservative treatments for a protruded disk were performed for 3 months before
      an accurate diagnosis was made. After correct diagnoses were made, excision of
      the femoral tumors brought rapid relief of all abnormal findings in both cases.
      Compared with other causes of sciatica, femoral bone tumors are rare. However,
      careful attention should be paid to rule out these lesions if the diagnosis of a
      lumbar spinal disease is uncertain. Bone scintigraphy seems to be a sensitive
      diagnostic method to detect extraspinal osseous lesions.

PMID- 10941899
TI  - CT-guided intraarticular injection of the sacroiliac joint.

PMID- 10941900
TI  - The immunological effects of taxanes.
AB  - In the past decade, taxanes have gained notoriety as promising chemotherapeutic
      agents against different forms of cancer. These molecules were initially
      characterized as mitotic inhibitors, and their anti-neoplastic actions were
      attributed to their ability to suppress cellular division via microtubule
      stabilization. Less appreciated is the observation that taxanes induce other
      biological effects, especially in the immune system. For example, taxanes are
      immunostimulatory against neoplasms, supporting the idea that these agents
      suppress cancer through several mechanisms and not solely through inhibiting cell
      division. In addition, these drugs potentially regulate other aspects of immune
      function, such as lymphocyte activation, giving further support to their
      immunomodulatory capacity. In summary, taxanes effect multiple actions and
      potentially have greater therapeutic application beyond cancer chemotherapy.

PMID- 10941901
TI  - Immunological properties of a single-chain fragment of the anti-idiotypic
      antibody ACA125.
AB  - Vaccination with anti-idiotypic antibodies has been described as a promising
      concept for treatment of several malignant diseases. The murine monoclonal anti
      idiotypic antibody ACA125 imitates a specific epitope of the tumor-associated
      antigen CA125 expressed by 80% of ovarian carcinomas. In the first clinical trial
      it could be shown that mAb ACA125 is able to elicit anti-anti-idiotypic
      antibodies (Ab3) with anti-CA125 specificity in patients with advanced ovarian
      cancer. In order to improve the capabilities of anti-idiotype vaccines we
      generated a genetically engineered single-chain fragment (scFv) ACA125 composed
      of heavy- and light-chain variable regions connected by a flexible linker. The
      antigenicity of scFv ACA125 was demonstrated by immunizing rats i.p. with scFv or
      complete mAb in complete/incomplete Freund's adjuvants (CFA/IFA) or precipitated
      by aluminium hydroxide. Negative control groups included applications of
      irrelevant mouse IgG or adjuvants alone. Anti-anti-idiotypic antibodies (Ab3)
      directed against the mAb ACA125 as well as specific anti-CA125 antibodies (Ab1')
      could be detected in all animals treated with scFv in CFA/IFA. Nevertheless,
      antibody titers were lower than when the complete mAb ACA 125 was used.
      Suprisingly, an increase of specificity could not be observed in scFv-immunized
      animals, which had been expected because of the lack of heavy- and light-chain
      constant regions that could raise rather unspecific anti-isotypic and anti
      allotypic rat anti-(mouse Ig) antibodies (RAMA). In contrast, the RAMA responses
      detected in these rats were even stronger than those following immunization with
      complete mAb ACA125. In conclusion, the anti-idiotypic scFv ACA125 alone cannot
      improve the immunogenic features of the corresponding mAb, but provides a useful
      tool for the further development of genetic vaccines.

PMID- 10941902
TI  - Influence of interferon gamma on modulation of Fas expression by human colon
      carcinoma cells and their subsequent sensitivity to antigen-specific CD8+
      cytotoxic T lymphocyte attack.
AB  - The inability of certain neoplastic populations to undergo Fas-mediated death by
      immune effector mechanisms may confer a selective survival advantage, which may
      contribute to tumor escape. In this study, we examined the role of Fas-mediated
      lysis in a human-antigen (Ag)-specific cytotoxic T lymphocyte (CTL)/colon
      carcinoma cell model, and the regulation of the lytic phenotype by interferon
      gamma (IFNgamma). Previously, we have identified mutated ras peptides reflecting
      the valine-for-glycine substitution at position 12 as unique HLA-A2-restricted,
      CD8+ CTL neo-epitopes. Peptide-specific CTL, established from both normal and
      carcinoma-bearing individuals, lysed in vitro a HLA-A2+ primary colon
      adenocarcinoma cell line, SW480, harboring the naturally occurring ras mutation.
      Pretreatment of SW480 cells with IFN-gamma was necessary to promote efficient Ag
      specific CTL killing, although the mechanisms by which IFNgamma influenced the
      lytic outcome remains to be elucidated. Here, we show, by phenotypic analysis of
      SW480 cells, a significant up-regulation of HLA-A2, ICAM-1 and Fas molecules
      after IFNgamma pretreatment, which paralleled their sensitivity to lysis with
      anti-Fas stimuli. Moreover, nearly half of the lytic response to IFNgamma-treated
      SW480 cells was inhibited by neutralizing anti-Fas or anti-Fasligand (FasL) mAb,
      revealing for the first time an important functional role for Fas/FasL
      interactions in carcinoma cell killing by human Ag-specific CTL. mAb against HLA
      A2, ICAM-1, the alpha T cell receptor (TCR) and Fas molecules inhibited lysis;
      however, if these CTL were preactivated to express functional FasL and then used
      as effectors, only anti-Fas mAb efficiently blocked lysis. IFNgamma also
      increased pro-caspase-3 protein expression and its subsequent activation in SW480
      cells following Ag-specific CTL attack. Peptide-based caspase inhibitors blocked
      both caspase-3 activation and CTL-mediated lysis. Overall, these data suggested
      that IFNgamma (a) facilitated both Ag-dependent and Ag-independent events as a
      prerequisite for efficient CTL/target interactions, FasL up-regulation and
      triggering of Fas-dependent, as well as Fas-independent lysis (perforin); and (b)
      enhanced or restored a Fas-sensitive phenotype in SW480 cells, reflecting
      modulation of cell-surface and intracellular elements of the Fas pathway. Thus,
      IFNgamma may play an important role in the regulation of a human neoplastic cell
      death phenotype, which may have implications for our understanding of the
      processes of both tumor evasion and tumor regression following Ag-specific CTL
      attack.

PMID- 10941903
TI  - Localization of an antibody to CD74 (MHC class II invariant chain) to human B
      cell lymphoma xenografts in nude mice.
AB  - The tumor-specific localization of an anti-CD74 Ab, LL1, was demonstrated in nude
      mice bearing xenografts of human B-cell lymphoma. This Ab, conjugated to
      radionuclides emitting Auger electrons, including 125I and 111In, was previously
      reported to kill tumor cells in vitro effectively and specifically. The cytotoxic
      potency of this Ab is due to its uptake and catabolism at a very high level,
      which also affected the Ab biodistribution experiments. Thus, Ab localization to
      the tumor was only detected if a "residualizing" radiolabel was used, meaning a
      label that is trapped within cells, usually within lysosomes, after catabolism of
      the Ab to which it was conjugated. Similar results were obtained with three
      different residualizing labels: 111In conjugated via the chelators benzyl
      diethylenetriaminepentaacetic acid (DTPA) or 1.4,7,10-tetra-azacyclododecane-N,
      N', N", N"'-tetraacetic acid (DOTA), or 131I-dilactitol-tyramine, a residualizing
      form of iodine. The Ab protein dose could be high, 0.5 mg/mouse, without causing
      a decrease in specific tumor uptake, probably reflecting the high capacity for
      uptake. Moreover, tumors of moderate size were found to cause rapid, specific
      removal of the Ab from the blood, also a result of catabolic processes. This
      induced blood clearance naturally affected the Ab localization experiments, but
      this factor could be circumvented by increasing the Ab protein dose. Using a
      different Ab, anti-(mature MHC class II), the ability of Ab to penetrate
      relatively large solid tumors was investigated. Complete saturation of antigenic
      sites was observed in tumors up to 0.3 g in size, but quite high Ab protein doses
      were required, 5.0 mg/ mouse. These results provide a rationale for attempting
      therapy with radiolabeled LL1.

PMID- 10941904
TI  - Noscapine inhibits tumor growth with little toxicity to normal tissues or
      inhibition of immune responses.
AB  - Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as
      an oral anti-tussive agent and has shown very few toxic effects in animals or
      humans. Recently, we reported that noscapine binds stoichiometrically to tubulin
      and promotes microtubule polymerization. Noscapine causes growth arrest of tumor
      cells in mitosis and induces apoptosis of tumor cells in vitro. Previous
      experiments also showed that noscapine has potent antitumor activity in mice when
      administered parenterally or by gastric lavage. Here, we report that the anti
      mitotic effect was specific to noscapine since closely related compounds did not
      inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to
      be effective in reducing the growth of the lymphoma and increasing the survival
      of tumor-bearing mice when administered in the drinking water. It is noteworthy
      that, noscapine showed little or no toxicity to kidney, liver, heart, bone
      marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral
      noscapine did not inhibit primary immune responses, which are critically
      dependent upon proliferation of lymphoid cells. Thus, our results indicate that
      noscapine has the potential to be an effective chemotherapeutic agent for the
      treatment of human cancer.

PMID- 10941905
TI  - Inhibition of tumor growth by poly(ethylene glycol) derivatives of anti-ErbB2
      antibodies.
AB  - Poly(ethylene glycol) (PEG) modification of substances with antitumor activity
      was shown to enhance penetration into growing solid tumors and extend antitumor
      effects. Accordingly, PEG was introduced as a modifier to two types of monoclonal
      antibodies (N12 and L26) specific to the ErbB2 (HER2) oncoprotein. These
      antibodies suppress the growth of tumors overexpressing ErbB2 (e.g. N87 human
      tumor) and the effect of PEG on their antitumor activity was evaluated. Methoxy
      PEG-maleimide conjugated to sulfhydryl groups at the hinge region of the
      antibodies impaired their antibody binding to N87 tumor cells and did not enhance
      the antitumor inhibitory activity in tumor-bearing mice. A branched N
      hydroxysuccinimide-activated PEG (PEG2), conjugated through amino groups of the
      protein, was used for binding to the whole antibody (Ab) or to its monomeric Fab'
      fragment. When tested against N87 cells in vitro, the binding activity and
      antitumor cytotoxic effects of Ab-PEG2 were mostly preserved. PEG2 modification
      did not seem to alter the tumor-inhibitory activity of the antibodies in vivo and
      the same pattern of tumor development was observed during the first few weeks
      following administration. However, the stimulating effects of PEG were observed
      at later stages of tumor growth since tumor development was either slowed down or
      completely arrested. Furthermore, a second tumor implanted into the same mice
      during this later stage was significantly or completely inhibited, as compared to
      results in mice injected with the unmodified antibody. The Fab'-PEG2 monomeric
      derivative was also shown to be effective in inhibiting the growth of a second
      tumor. The extended and prolonged enhancing effect of PEG on the antitumor
      activity of antibodies or Fab' fragments directed against ErbB2 may be of
      importance in the treatment of ErbB2-overexpressing neoplasms.

PMID- 10941906
TI  - Functional assessment in vitro of human-complement-dependent antibody-induced
      cytotoxicity of neoplastic cells.
AB  - The complement system is one potential cytotoxic effector mechanism that might be
      effective in immunotherapy of cancer using monoclonal antibodies (mAb) directed
      against tumor antigens. In order to evaluate the treatment outcome from trials
      using mAb in cancer patients, assessment of complement-dependent cytotoxicity
      (CDC) may therefore be of interest. Here we describe the elaboration of a CDC
      assay in vitro using a rat hepatoma cell line, H4-II-E, as target cells
      sensitised with mAb F12, directed against the tumor-associated ganglioside
      antigen fucosyl-GMI. Sensitised cells were incubated with various concentrations
      of fresh serum as complement source for 48 h and cytotoxicity was then assessed
      by the tetrazolium bromide (MTT) test. A large variation in CDC efficacy was
      observed between individual serum donors. No differences in CDC could be seen
      between healthy donors and cancer patients. The CDC showed a strong correlation
      to the serum concentrations of complement factor C4, supporting the validity of
      the assay. Our results suggest that there may be significant variations in
      complement function within and between individuals that might influence the
      outcome of clinical mAb therapy. The H4/F12 CDC assay described here, together
      with measurement of individual complement factors. such as C4, should be further
      validated in cancer patients at various disease stages and phases of treatment.

PMID- 10941907
TI  - Single-chain antibodies against human insulin-like growth factor I receptor:
      expression, purification, and effect on tumor growth.
AB  - Insulin-like growth factors (IGF) I and II are potent mitogens for a variety of
      cancer cells. The proliferative and anti-apoptotic actions of IGF are mediated by
      the IGF-I receptor (IGF-IR), to which both IGF-I and IGF-II bind with high
      affinity. To investigate the mitogenic and anti-apoptotic activities of IGF-IR
      and to achieve better inhibition of IGF-IR function, single-chain antibodies
      against human IGF-IR (alphaIGF-IR scFvs) were constructed and expressed. IgG cDNA
      encoding variable regions of light and heavy chains (VL and VH) from mouse IgG
      were cloned from a hybridoma producing the 1H7 alphaIGF-IR monoclonal antibody
      [Li et al., Biochem Biophys Res Commun 196: 92-98 (1993)]. The splice-overlap
      extension polymerase chain reaction was used to assemble a gene encoding the
      alphaIGF-IR scFv, including the N-terminal signal peptide, VL, linker peptide,
      VH, and C-terminal DYKD tag. Two types of soluble alphaIGF-IR scFvs, a prototype
      alphaIGF-IR scFv and its alternative type alphaIGF-IR scFv-Fc, were constructed
      and expressed in murine myeloma cells. alphaIGF-IR scFv-Fc, containing the human
      IgG1 Fc domain, was stably expressed in NS0 myeloma cells, using a glutamine
      synthase selection system, and purified from the conditioned medium of stable
      clones by protein-A--agarose chromatography. Levels of alphaIGF-IR scFv-Fc
      expression ranged from 40 mg/l to 100 mg/l conditioned medium. Sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis analysis under reducing and
      nonreducing conditions indicated that alphaIGF-IR scFv-Fc is a dimeric antibody.
      alphaIGF-IR scFv-Fc retained general characteristics of the parental 1H7
      monoclonal antibody except that its binding affinity for IGF-IR was estimated to
      be approximately 10(8) M(-1), which was one-order of magnitude lower than that of
      1H7 monoclonal antibody. Injection of alphaIGF-IR scFv-Fc (500 microg/mouse,
      twice a week) significantly suppressed MCF-7 tumor growth in athymic mice. These
      results suggest that the alphaIGF-IR scFv-Fc is a first-generation recombinant
      alphaIGF-IR for the potential development of future alphaIGF-IR therapeutics.

PMID- 10941908
TI  - Therapeutic potential of chimeric anti-(ganglioside GD3) antibody KM871:
      antitumor activity in xenograft model of melanoma and effector function analysis.
AB  - KM871 is a chimeric antibody recognizing ganglioside GD3, which is one of the
      major gangliosides expressed on the cell surface of human tumors of
      neuroectodermal origin. This study demonstrates the antitumor activity of KM871
      against human melanoma xenografts in nude mice, and analyzes the effector
      function operating in mice. In a well-established tumor model, KM871 showed
      antitumor activity against H-15 and SK-MEL-28 human melanoma but not against H
      187 and G361 human melanoma when administered intravenously 5 days/week for 2
      weeks. The G361 tumor became sensitive when KM871 was first administered on the
      day of tumor inoculation. In this assay, it was observed that almost all the mice
      were tumor-free, but a few mice developed tumors. Therefore, we examined the
      amount and expression pattern of GD3 antigen on G361 tumors escaping from KM871
      treatment, but no change was observed. Next we examined the optimal
      administration schedule for KM871 in mice, using H-15 melanoma. KM871 showed
      antitumor activity when administered intravenously either 5 days/week for 2 weeks
      or three biweekly doses. However, the effect of the former schedule was stronger
      than three biweekly doses. To compare the effector function in humans and mice,
      we studied the complement-mediated cytotoxicity, antibody-dependent cell-mediated
      cytotoxicity and antibody-dependent macrophage-mediated cytotoxicity of KM871
      using complement or effector cells prepared from humans and mice. It was found
      that the antibody-dependent cell-mediated cytotoxicity exerted by
      polymorphonuclear cells and antibody-dependent macrophage-mediated cytotoxicity
      were the only antitumor mechanism of KM871 in mice. However their action was very
      weak compared with that in humans, and complement-mediated cytotoxicity, which
      was strong in humans, was not observed in mice. Therefore, the antitumor activity
      of KM871 against human melanomas evaluated by the nude mouse model might be
      underestimated. These results indicate that KM871 shows good antitumor activity
      against GD3-positive human melanoma and the antitumor activity expected in humans
      might be superior to that of the nude mouse model.

PMID- 10941909
TI  - Comparison of in vitro antibody-targeted cytotoxicity using mouse, rat and human
      effectors.
AB  - Antibodies can direct tumor cell lysis by activating complement-mediated and cell
      mediated cytoxicities (antibody-dependent cell-mediated cytotoxicity, ADCC).
      Clinical translation of these effects into successful cancer therapy has been
      slow. Choosing an appropriate animal model to test new therapeutic strategies is
      difficult because of species differences in immunological effector functions. In
      previous work, we found that an unmodified anti-ganglioside mouse IgG3 monoclonal
      antibody (mAb), 3F8, could successfully treat clinical tumors in humans and
      experimental tumors in rats but not experimental tumors in mice. We explored the
      reasons for this species difference by performing in vitro antibody-dependent
      cytotoxicity assays comparing the potency of polymorphonuclear neutrophils (PMN),
      natural killer (NK) cells and complement from the three species: mouse, rat and
      human. 3F8-dependent complement-mediated cytotoxicity produced more than 70%
      specific release when human and rat sera were used and only 20% with mouse serum.
      PMN-mediated ADCC was 35%-70% with human effectors, 25%-60% with rat and
      undetectable with mouse. Human eosinophils did not contribute to this ADCC.
      Cytotoxicity utilizing interleukin-2-activated NK cells was antibody-independent
      in all three species but the specific release was 60%-70% with human and rat NK
      cells and 10% with mouse NK cells. These data suggest that, for mouse IgG3, the
      rat may provide a more relevant rodent model than the mouse for testing the in
      vivo antitumor effects of monoclonal antibodies.

PMID- 10941910
TI  - Pharmacokinetics and biodistribution of a light-chain-shuffled CC49 single-chain
      Fv antibody construct.
AB  - Murine monoclonal antibodies to tumor-associated glycoprotein 72 (anti-TAG-72 mAb
      B72.3 and CC49) are among the most extensively studied mAb for immunotherapy of
      adenocarcinomas. They have been used clinically to localize primary and
      metastatic tumor sites; however, murine mAb generally induce potent human anti
      (mouse antibody) responses. The immunogenicity of murine mAb can be minimized by
      genetic humanization of these antibodies, where non-human regions are replaced by
      the corresponding human sequences or complementary determining regions are
      grafted into the human framework regions. We have developed a humanized CC49
      single-chain antibody construct (hu/muCC49 scFv) by replacing the murine CC49
      variable light chain with the human subgroup IV germline variable light chain
      (Hum4 VL). The major advantages of scFv molecules are their excellent penetration
      into the tumor tissue, rapid clearance rate, and much lower exposure to normal
      organs, especially bone marrow, than occur with intact antibody. The biochemical
      properties of hu/muCC49 scFv were compared to those of the murine CC49 scFv
      (muCC49 scFv). The association constants (Ka) for hu/muCC49 and muCC49 constructs
      were 1.1 x 10(6) M(-1) and 1.4 x 10(6) M(-1) respectively. Pharmacokinetic
      studies in mice showed similar rapid blood and whole-body clearance with a half
      life of 6 min for both scFv. The biodistribution studies demonstrated equivalent
      tumor targeting to human colon carcinoma xenografts for muCC49 and hu/ muCC49
      scFv. These results indicate that the human variable light-chain subgroup IV can
      be used for the development of humanized or human immunoglobulin molecules
      potentially useful in both diagnostic and therapeutic applications with TAG-72
      positive tumors.

PMID- 10941911
TI  - New methods to approach immunotherapy of cancer--and strategies of tumours to
      avoid elimination. Conference report, on behalf of EUCAPS. European Cancer
      Research Consortium.
AB  - Owing to the intense effort of numerous investigators, the number of tumour
      antigens potentially of use for clinical immunotherapy continues to increase. At
      the same time, further strategies employed by tumour cells to avoid destruction
      by the immune system are being uncovered. A combined onslaught to target tumour
      cells and prevent their "escape" will be required for successful immunotherapy.
      Progress in this area was the subject of a meeting supported by the European
      Cancer Research Consortium "EUCAPS", which was held in London in February 2000.
      This conference was the second of a series, the first of which was summarised
      previously in this journal [Pawelec G et al. (1999) Cancer Immunol Immunother 48:
      214].

PMID- 10941912
TI  - Conference on cancer vaccines.

PMID- 10941913
TI  - Porous carriers for biomedical applications based on alginate hydrogels.
AB  - Macroporous scaffolds are typically utilized in tissue engineering applications
      to allow for the migration of cells throughout the scaffold and integration of
      the engineered tissue with the surrounding host tissue. A method to form
      macroporous beads with an interconnected pore structure from alginate has been
      developed by incorporating gas pockets within alginate beads, stabilizing the gas
      bubbles with surfactants, and subsequently removing the gas. Macroporous
      scaffolds could be formed from alginate with different average molecular weights
      (5-200 kDa) and various surfactants. The gross morphology, amount of
      interconnected pores, and total void volume was investigated both qualitatively
      and quantitatively. Importantly, macroporous alginate beads supported cell
      invasion in vitro and in vivo.

PMID- 10941914
TI  - Structural response and relative strength of a laminated composite hip
      prosthesis: effects of functional activity.
AB  - To obtain a better appreciation for the structural performance of a laminated
      composite hip prosthesis (CP), we examined in situ prosthesis structural response
      and relative strengths as a function of walking and stair climbing using our
      previously developed analysis guidelines. Accordingly, we examined overall
      prosthesis structural response utilizing a global continuum level modeling
      approach and prosthesis relative strengths using a local microstructural (or ply
      level) modeling approach. As a reference and control, we examined the structural
      performance of the intact natural femur (NAT) and a titanium alloy (Ti) based hip
      prosthesis. In terms of the overall structural response, i.e., the
      femur/prosthesis deformational response, stem/bone interfacial stress transfer,
      and calcar strain energy density restored, the performance of the CP prosthesis
      was moderately improved over that of the control Ti prosthesis and better
      approximates the NAT response. In terms of relative strength, we found that the
      neck of the CP prosthesis failed for all activities with the exception of the mid
      stance phase of level walking. However, the prosthesis appears to have sufficient
      relative strength for function at positions distal to the neck of the prosthesis.
      While these results dampen enthusiasm for consideration of laminated composite
      hip prostheses designed with a shape based on a metal alloy implant, they
      indirectly support consideration of alternate hip prosthesis structural designs
      such as using a better supported prosthesis neck or utilizing metal/composite
      hybrid constructions. Importantly, our simulation and analysis approach could be
      utilized in the design of other laminated composite biomedical structural
      components.

PMID- 10941915
TI  - Synthesis and degradation characteristics of salicylic acid-derived
      poly(anhydride-esters).
AB  - A biodegradable poly(anhydride-ester) was synthesized by melt condensation
      polymerization of the acetylated monomer to yield a novel polymeric prodrug. The
      polymer we have synthesized is composed of alkyl chains linked by ester bonds to
      aromatic moieties, specifically salicylic acid--the active component of aspirin.
      With the medicinal properties attributed to salicylic acid and the ease of
      metabolism, the incorporation of this compound into a polymer backbone yields a
      polymeric prodrug that may have potential in a variety of applications (i.e.,
      inflammatory bowel disease). For these reasons, we have designed a synthetic
      scheme that yields the desired poly(anhydride-ester). The in vitro hydrolytic
      degradation of these polymers has been performed and results indicate that the
      polymer degradation rate is pH-dependent.

PMID- 10941916
TI  - A comparison of the inflammatory response to a polydimethylsiloxane implant in
      male and female Balb/c mice.
AB  - The implantation of biomaterials elicits a host response that influences the long
      term behavior of implanted medical devices. This foreign body response is
      governed by cells of the immune system. Because sexual dimorphism in the immune
      system is well-established, a comparative study of the foreign body response in
      male and female mice was initiated. Eight-week-old male and female Balb/c mice
      received two subcutaneous implants in the interscapular region of a smooth
      peroxide-catalyzed polydimethylsiloxane (PDMS) and were sacrificed at 2, 14, 42,
      70, and 105 days after implantation (n = 6 per sex per time point). Controls for
      each time point underwent the surgical procedure but received no implant. Tissue
      from the implant or surgical site was fixed, processed, and paraffin-embedded for
      histopathological evaluation and immunohistochemical (IHC) staining for tumor
      necrosis factor-alpha TNF-alpha) and interleukin-1 beta (IL-1beta). In control
      animals, an inflammatory response was observed at 2 days that was decreased by 14
      days and absent after 42 days. At 2 and 14 days after PDMS implantation, a mild
      to moderate inflammatory reaction was observed around implants. The peak response
      was seen at 14 days, and granulation tissue, composed primarily of fibroblasts,
      macrophages, and neutrophils, was first observed at this time. After 105 days,
      the implantation site was surrounded by mature connective tissue, which had
      minimal numbers of macrophages and neutrophils, with severity scores that did not
      differ significantly in males and females. The immunostaining for TNF-alpha and
      IL-1beta followed similar temporal patterns, with both reaching a peak at the two
      week time point and remaining elevated, compared to level of expression in the
      controls, throughout the 105 day observation period. Staining for both cytokines
      in the implanted animals was generally higher in females than in males, although
      this difference was significant only for IL-1beta. These results suggest subtle
      differences between males and females in the activity of peri-implant
      inflammatory cells.

PMID- 10941917
TI  - Paclitaxel loaded poly(L-lactic acid) microspheres for the prevention of
      intraperitoneal carcinomatosis after a surgical repair and tumor cell spill.
AB  - A controlled release delivery system for paclitaxel was developed using poly(L
      lactic acid) to provide local delivery to the peritoneal cavity. Microspheres
      were made in 1-40 and 30-120 microm size ranges. In an in vitro release study, 30
      120 microm microspheres loaded with 10, 20 and 30% paclitaxel exhibited a burst
      phase of release for 3 days followed by an apparently zero-order phase of
      release. At all loadings, 20-25% of the original load of paclitaxel was released
      after 30 days. The effect of microsphere size on retention in the peritoneal
      cavity was assessed. Control 1-40 microm microspheres were injected
      intraperitoneally in rats. The rats received either insufflation of the
      peritoneal cavity using 11 mmHg CO2 or no further treatment. After sacrifice,
      microspheres with diameters less than 24 microm were observed in the lymphatic
      system after being cleared from the peritoneal cavity through fenestrations in
      the diaphragm. Insufflation of the peritoneal cavity had no effect on the size of
      microspheres that were cleared. Efficacy studies were carried out using 30-120
      microm microspheres that were of sufficient size to be retained in the peritoneal
      cavity. In a model of a tumor cell spill after a cecotomy repair, 100 mg of 30
      120 microm microspheres containing 30% paclitaxel were effective in preventing
      growth of tumors in the peritoneal cavity at both 2 and 6 weeks post-surgery. No
      gross or histologically evident tumor growth was observed on any peritoneal
      surfaces or in the surgical wound site. Rats receiving control microspheres all
      showed tumor cell implantation and growth after 2 weeks.

PMID- 10941918
TI  - Use of Raman spectroscopy in the characterisation of the acid-base reaction in
      glass-ionomer cements.
AB  - Raman spectra of various combinations of glass-ionomer cement components have
      been compared with those of the reactants and the salts of polyacrylic and
      tartaric acids. The components consisted of a fast-setting acid-degradable dental
      glass (containing, inter alia, oxides of Si, Al, Ca, Ba and Na), polyacrylic acid
      (PAA) and/or tartaric acid (TA). On the addition of water to the glass and
      tartaric acid, Raman spectroscopy indicated loss of acid and production of
      tartrate salts within seconds of mixing. Mixtures containing the glass, PAA and
      water in mass ratios 2:1:(0.1-4) reacted to form polyacrylate salts. The maximum
      fraction of unreacted PAA was found to decrease linearly with initial water/PAA
      mass ratio to a minimum of approximately 20% when this ratio exceeds 1.5. The
      data are consistent with 5.6 moles of water being required when each mole of
      acidic groups is neutralised. In newly prepared cements containing glass, water,
      polyacrylic and tartaric acids, polyacrylic acid and its salts, in both ionised
      and solid state form, can be detected. After about 1 h, however, Raman peaks
      associated with ionised species disappear.

PMID- 10941919
TI  - Surface roughness, porosity and wettability of gentamicin-loaded bone cements and
      their antibiotic release.
AB  - In this study, the release of gentamicin as a function of time was measured for
      six different gentamicin-loaded bone cements and related with the surface
      roughness, porosity and wettability of the cements. Initial release rates varied
      little between the six bone cements (CMW1, CMW3, CMW Endurance, CMW 2000,
      Palacos, and Palamed) and ranged from 8.6 to 14.1 microg/cm2/h. The total amounts
      of gentamicin released after 1 week varied between 4.0 and 5.3% of the total
      amount of antibiotic incorporated for the CMW cements and was 8.4% for Palacos.
      Palamed released after 1 week significantly more of the gentamicin incorporated
      (17.0%). The wettability of all cements was similar (water contact angles between
      70 and 80 degrees), but the surface roughness and the porosity of the cements
      varied markedly. Initial release rates increased with surface roughness, although
      the correlation coefficient was low (0.64), while total amounts released
      increased linearly (correlation coefficient 0.97) with the bulk porosity of the
      cements. Consequently, it can be concluded that the release kinetics of
      gentamicin from bone cements is controlled by a combination of surface roughness
      and porosity.

PMID- 10941920
TI  - The rate of change of pH of lactic acid exposed to glass-ionomer dental cements.
AB  - The rate of change of pH of aqueous lactic acid at pH 4.2-4.5 (i.e. a little
      below that of active caries in vivo) in contact with disks of various commercial
      glass-ionomer cements has been determined in two configurations. In the first of
      them, a thin film set-up, 20 microl of solution was spread across the surface of
      a cement disk (diameter: 13 mm), and its pH determined by pressing a flat-ended
      electrode against the film at varying time intervals. In the second, a similar
      disk was immersed in 1.5 ml of solution, removed after varying time intervals,
      after which the pH of the solution was measured using a round-ended electrode.
      The latter measurement was more reliable, in that the pH electrode had time to
      equilibrate, whereas the former was more realistic because the film was
      approximately the same thickness as that of saliva on a tooth surface. Both
      series of experiments showed measurable differences in pH after only 30 s, with
      the thin-film configuration showing a range of pH changes of 0.5-1.2 units
      depending on the cement and the small volume configuration showing a range of 0.1
      0.5 units, also depending on the cement. After 10 min, in the small volume
      experiments, the pH had generally increased further. The extent and speed of the
      change in pH led to the conclusion that ability of glass-ionomers to increase pH
      is likely to be an important mechanism of caries protection under clinical
      conditions.

PMID- 10941921
TI  - Effect of TiO2-Ag2O additives on the formation of calcium phosphate based
      functionally graded bioceramics.
AB  - The combined effect of titanium dioxide and silver oxide on the in situ formation
      of biphasic calcium phosphate ceramics was investigated. Titania (5-20 mol%) was
      mixed with pure hydroxyapatite (HA) or HA containing Ag2O (10-20 mol%) and was
      heated to 900 degrees C for 12 h. The sintered samples were found to contain
      tricalcium phosphate (beta-TCP) and other phases along with HA depending upon the
      amount as well as the type of the additives used as evidenced by X-ray powder
      diffraction (XRD) and fourier transform infrared (FT-IR) spectroscopic studies.
      Enhanced TCP formation with reduced impurity phases was observed with TiO2-Ag2O
      addition. In vitro solubility study in phosphate buffer at physiological
      conditions shows the resorbable nature of these materials. A functionally graded
      material (FGM) structure was formed by spreading TiO2-Ag2O mixture on the surface
      of the HA green compact and heating at 900 degrees C. The FGM shows gradient
      structure of TCP and HA from the surface to the interior of the pellet in
      addition to titania and silver phases.

PMID- 10941922
TI  - Bone formation in calcium-phosphate-coated titanium mesh.
AB  - The osteogenic activity of porous titanium fiber mesh and calcium phosphate (Ca
      P)-coated titanium fiber mesh loaded with cultured syngeneic osteogenic cells was
      compared in a syngeneic rat ectopic assay model. In 30 syngeneic rats, (Ca-P)
      coated and non-coated porous titanium implants were subcutaneously placed either
      without or loaded with cultured rat bone marrow (RBM) cells. Fluorochrome bone
      markers were injected at 2, 4, and 6 weeks. The rats were sacrificed, and the
      implants were retrieved at 2, 4, and 8 weeks post-operatively. Histological
      analysis demonstrated that none of the (Ca-P)-coated and non-coated meshes alone
      supported bone formation at any time period. In RBM-loaded implants, bone
      formation started at 2 weeks. At 4 weeks, bone formation increased. However, at 8
      weeks bone formation was absent in the non-coated titanium implants, while it had
      remained in the (Ca-P)-coated titanium implants. Also, in (Ca-P)-coated implants
      more bone was formed than in non-coated samples. In general, osteogenesis was
      characterized by the occurrence of multiple spheres in the porosity of the mesh.
      The accumulation sequence of the fluorochrome markers showed that the newly
      formed bone was deposited in a centrifugal manner starting at the center of a
      pore. Our results show that the combination of Ti-mesh with RBM cells can indeed
      generate bone formation. Further, our results confirm that a thin Ca-P coating
      can have a beneficial effect on the bone-generating properties of a scaffold
      material.

PMID- 10941923
TI  - Effect of a neutral citrate solution on the fluoride release of resin-modified
      glass ionomer and polyacid-modified composite resin cements.
AB  - The effect of 0.01 mol/l citrate solution at pH = 7 on the fluoride release is
      compared for the resin-modified glass ionomer cements (RM-GIC) GC Lining LC,
      PhotacBond, Vitremer and Vitrebond and for the polyacid-modified composite resins
      (PAM-C) Variglass and Dyract by means of the six-month fluoride release profiles
      at 37 degrees C. The fluoride release of both RM-GIC and PAM-C increases in the
      neutral citrate solution as compared to water, which can be explained by the
      ability of citrate to complex metal ions and hence to degrade the glass as well
      as the polysalt matrix of the cement. Although RM-GIC release more fluoride than
      PAM-C in water as well as in citrate solution, the relative increase in fluoride
      release upon immersion in citrate solution is most pronounced for PAM-C. Whereas
      for the latter citrate affects both the short-term and long-term fluoride
      release, for RM-GIC only the long-term fluoride release is affected. This
      suggests that the action of citrate increases with decreasing importance of the
      polysalt formation in the hardening of the material. This could be explained on
      the basis of the difference in the chemical properties of the cement matrix.

PMID- 10941924
TI  - Interspecies transmission and receptor recognition of influenza A viruses.

PMID- 10941925
TI  - Dithiothreitol enhances Listeria monocytogenes mediated cell cytotoxicity.
AB  - The hybridoma Ped-2E9 based cytotoxicity assay was developed to distinguish
      virulent from avirulent Listeria species in 6 hr. The cytotoxicity effect on Ped
      2E9 was reported to be primarily due the cytolytic action of listeriolysin O
      (LLO), produced by L. monocytogenes. In this study, the effect of a reducing
      agent, dithiothreitol (DTT, 0-2 mM) that is known to activate LLO was
      investigated to make the Ped-2E9 based cytotoxicity assay an even more sensitive
      and rapid. Also, we examined the effect of fetal bovine serum (FBS, 0-50%), a
      common ingredient of tissue culture media on cytotoxicity. A DTT concentration of
      0.5 mM gave an optimum cytotoxicity effect, which could be measured by both
      alkaline phosphatase (AP) and lactate dehydrogenase (LDH) assays in just 1.5-2
      hr. FBS, at levels between 10 to 50%, significantly inhibited Listeria-mediated
      cytotoxicity. Concentrated culture filtrates from L. monocytogenes or LLO
      producing recombinant L. innocua (prfA+ hlyA+) strain also caused cytotoxicity
      effects, which were observed by scanning electron microscopy or a cytotoxicity
      assay in 2-3 hr. Interestingly, addition of DTT to culture filtrates produced
      100% cell cytotoxicity in just 15 min. This indicated that LLO activity, which is
      responsible for Ped-2E9 cytotoxicity, was augmented several folds with the
      addition of a reducing agent. Examination of Listeria isolates belonging to
      different serogroups from clinical sources or naturally contaminated meat
      products with DTT gave cytotoxicity results in 2 hr, which were comparable to the
      5-hr assay analyzed concurrently without DTT. These results indicated that DTT,
      which activated the LLO, could be used in the cytotoxicity assay to enhance
      Listeria-mediated Ped-2E9 cell cytotoxicity. This knowledge will greatly assist
      us to develop a user-friendly rapid assay to screen cytopathogenic properties of
      Listeria species.

PMID- 10941926
TI  - Development of hyperfimbriated strains of Vibrio cholerae O1.
AB  - The Vibrio cholerae O1 and O139 fimbrillin genes (fimA or mshA) were amplified by
      polymerase chain reaction and cloned into an Escherichia coli pCR vector. These
      clones were sequenced. The fimA sequences were found to be identical between V
      cholerae O1 and O139. One of the plasmids was digested with EcoR I and inserted
      into the EcoR I site of pGEX-3X. The plasmid pVPP thus obtained was transferred
      into strains of wild-type V cholerae O1 Bgd17 (classical in biotype) and its
      fimbriated strain by electroporation. The recombinant plasmid pVPP overexpressed
      mature fimbriae following induction of the tac promoter with isopropyl-beta-D
      thiogalactopyranoside. The cloned gene product was purified to homogeneity by
      sucrose-linear gradient centrifugation (7.8 mg of fimbriae/L-culture). All the
      properties of the recombinant fimbriae (e.g., subunit structure, hydrophobicity,
      hemagglutinating activity sensitive to D-mannose and D-glucose and
      immunogenicity) were identical to those of the wild-type fimbriae. This
      overexpression system will be extremely useful for rapid, inexpensive preparation
      of large amounts of fimbriae for vaccine design and development.

PMID- 10941927
TI  - Constitutively expressed phoP inhibits mouse-virulence of Salmonella typhimurium
      in an Spv-dependent manner.
AB  - In Salmonella typhimurium, the transcription of several virulence genes including
      spvB is regulated by the PhoP/PhoQ regulatory system. To further examine the
      relationship between the PhoP/PhoQ and Spv systems for virulence in mice, we
      examined a non-polar phoP mutation combined with different virulence plasmid
      genotypes for effects on virulence of S. typhimurium in the mouse model. PhoP
      /Spv+ and PhoP-/Spv- mutants were not detectably recovered from the spleens of
      subcutaneously or orally inoculated mice. The phoP gene constitutively expressed
      from the lacZ promoter of a low copy number vector (phoP(C)) only partially
      complemented the non-polar phoP mutation for mouse-virulence in both the Spv+ and
      Spv- backgrounds; both PhoP(C) strains exhibited virulence equal only to a
      PhoP+/Spv- strain. Interestingly, in a PhoP+ background, the phoP(C) gene reduced
      splenic infection of the Spv+ but not Spv- salmonellae after subcutaneous or oral
      inoculation compared with the PhoP+ parents. Additionally, the phoP(C) gene in an
      Spv+ background reduced the net growth of salmonellae in macrophages in vitro;
      phoP(C) in an Spv- background was without effect. These data suggest that the
      constitutive expression of the phoP gene attenuates the virulence of S.
      typhimurium in mice in an Spv-dependent manner.

PMID- 10941928
TI  - Phylogenetic and taxonomic heterogeneity of Cryptococcus humicolus by analysis of
      the sequences of the internal transcribed spacer regions and 18S rDNA, and the
      phylogenetic relationships of C. humicolus, C. curvatus, and the genus
      Trichosporon.
AB  - The phylogenetic and taxonomic heterogeneity of a rare opportunistic yeast
      pathogen, Cryptococcus humicolus, was revealed by analysis of the sequence of the
      internal transcribed spacer (ITS) region. Sixteen strains of C. humicolus showed
      a wide diversity in their ITS sequences. In addition, their 18S rDNA sequences
      were determined and used to analyze the phylogenetic relationships among C.
      humicolus and related yeasts. On trees constructed by the Neighbor-Joining and
      Maximum Parsimony methods, C. humicolus strains were phylogenetically closely
      related to each other with the exception of one strain, and they clustered with
      C. curvatus and Trichosporon species with high bootstrap values. Three C.
      humicolus strains obtained from humans belonged to the group of Trichosporon
      serotype I species. The results suggest that C. humicolus is a genetically
      heterogeneous species which should be reclassified on the basis of DNA sequence
      data.

PMID- 10941929
TI  - Modification of autolysis by synthetic peptides derived from the presumptive
      binding domain of Staphylococcus aureus autolysin.
AB  - The autolytic cell wall hydrolase of Staphylococcus aureus, Atl, contains three
      highly cationic repeats in the central region of the amino acid sequence, and the
      repeats are presumed to have the role of binding the enzyme to some components on
      the cell surface. To explain the possible function of the repeats, we synthesized
      a number of 10- to 30-mer oligopeptides based on the Atl amino acid sequence
      (Thr432-Lys610) containing repeat 1, and examined their effects on the autolysis
      of S. aureus cells. When the peptides were added to a cell suspension of S.
      aureus under low ionic strength conditions, five peptides, A10, A11, A14, A16 and
      B9, showed immediate increases in optical density (OD) of the cell suspension
      accompanied by decreases in viable cell counts. After the immediate increases,
      the ODs for A10 and A14 changed little in the first 2 hr. In contrast, the ODs
      for A11 and A16 decreased rapidly. When peptide A10 was added to suspensions of
      heat-killed whole cells, crude cell walls and a crude peptidoglycan preparation,
      their ODs were increased approximately 2-fold. In contrast, the OD was not
      increased when the peptide was added to a suspension of pure peptidoglycan from
      which anionic polymers had been removed. Light microscopic and transmission
      electron microscopic study showed that A10 and A14 inhibited autolysis and that
      A11 and A16 induced autolysis earlier than the control. These results suggest
      strongly that the peptides adsorb to and precipitate on the anionic cell surface
      polymers such as teichoic acid and lipoteichoic acid via ionic interaction. The
      effects of peptides on the autolysis may be the results of the modification of S.
      aureus autolysin activities. These peptides, especially the 10-mer peptide B9
      (PGTKLYTVPW) that represents the C-terminal half of A10 and N-terminal half of
      A11, may be important segments for Atl to bind to the cell surface.

PMID- 10941930
TI  - Blockade of Salmonella enteritidis passage across the basolateral barriers of
      human intestinal epithelial cells by specific antibody.
AB  - Antibodies specific to Salmonella enteritidis (S.E.) were obtained from immunized
      egg yolk, and their protective effects against S.E. were studied by using
      monolayer-cultured human intestinal epithelial cells, Caco-2 and T84. The
      Salmonella adherence and entry to the cells were partially inhibited by the
      antibodies. The antibodies inhibited the decrease in transepithelial electrical
      resistance (TEER) of the intestinal epithelial monolayers and IL-8 secretion of
      the cells induced by S.E. invasion. Also, the antibodies blocked the penetration
      of bacteria through the cell layer although they did not inhibit the growth of
      bacteria in the cells. Confocal microscopic photographs revealed the bacteria in
      the infected monolayer cells were bound to antibodies. These results indicate
      that anti-S.E. antibodies may protect the cells from destruction induced by S.E.
      invasion in intestinal epithelial cells in addition to the partial inhibition of
      adhesion and invasion of S.E. at the cell surface. Passive antibodies against
      invasive bacteria would be useful to prevent the migration of S.E. to blood not
      only at the cell surface but also inside of intestinal epithelial cells.

PMID- 10941931
TI  - Mutation of aromatic amino acid residues located at the amino- and carboxy
      termini of Escherichia coli heat-stable enterotoxin Ip reduces the efficiency of
      the toxin to cross the outer membrane.
AB  - Heat-stable enterotoxin Ip (STIp) of Escherichia coli is synthesized as a
      precursor form consisting of pre- (amino acid residues 1 to 19), pro- (amino acid
      residues 20 to 54) and mature (amino acid residues 55 to 72) regions. Mature STIp
      (bioactive STIp) is formed in the periplasmic space after the precursor is
      proteolytically processed and the mature STIp translocates across the outer
      membrane through the secretory system including TolC, an outer membrane protein
      of E. coli. However, it remains unknown how the mature STIp is recognized by this
      secretory system. In this study, we investigated the amino acid residues of STIp
      involved in its translocation across the outer membrane. We prepared mutant STIp
      genes by site-directed mutagenesis and analyzed translocation of the mutant STIps
      across the outer membrane. Deletion of the Phe or Tyr residue at position 3 or
      18, respectively, decreased the efficiency of translocation of STIp across the
      outer membrane. To confirm the involvement of these amino acid residues, we
      further mutated the codons for these amino acid residues to that for Gly. These
      mutations also decreased the efficiency of extracellular secretion of STIp. In
      contrast, substitution of Phe-3 and Syr-18 with Tyr and Phe, respectively, did
      not affect the efficiency of translocation of the toxin. These results indicated
      that the aromatic amino acid residues at positions 3 and 18 in the mature region
      are important for the ability of STIp to cross the outer membrane.

PMID- 10941932
TI  - Differential level in co-down-modulation of CD4 and CXCR4 primed by HIV-1 gp120
      in response to phorbol ester, PMA, among HIV-1 isolates.
AB  - HIV-1 enters cells through interacting with cell surface molecules such as CD4
      and chemokine receptors. We generated recombinant soluble gp120s derived from T
      cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) HIV-1 strains using
      a baculovirus expression system and investigated the association of CD4-gp120
      complex with the chemokine receptor and/or other surface molecule(s). For
      monitoring the co-down-modulations of the CD4-gp120 complex, a cytoplasmic domain
      deletion mutant (tailless CD4), which is not capable of undergoing down
      modulation by itself in response to phorbol ester PMA, was used. Our studies
      revealed both cell-type and HIV-1 strain-specific differences. We found that T
      tropic gp120s were capable of priming co-down-modulation with tailless CD4 by
      interacting with CXCR4, whereas M-tropic SF162 gp120 could not after PMA
      treatment even in the presence of CCR5. Among the T-tropic HIV-1 envelopes, IIIB
      gp120 was the most potent. Furthermore, the ability of gp120 to prime the PMA
      induced co-down-modulation of tailless CD4 appeared to be dependent on the
      concentration of the principal coreceptor CXCR4. Nevertheless, the observation
      that IIIB gp120 strongly primed tailless CD4 co-down-modulation on human
      osteosarcoma HOS cells that express undetectable levels of surface CXCR4 raised
      the possibility that membrane component(s) other than those recently identified
      can be involved in down-modulation of the CD4/gp120 complexes.

PMID- 10941933
TI  - The relative frequencies of G serotypes of rotaviruses recovered from
      hospitalized children with diarrhea: A 10-year survey (1987-1996) in Japan with a
      review of globally collected data.
AB  - Since rotavirus vaccines aim to protect children from severe diarrhea, knowledge
      of the prevailing G serotypes among rotaviruses from hospitalized children is
      essential. Thus, we determined the G serotypes of rotaviruses collected from
      children with acute diarrhea in a local referral hospital in Akita, Japan, over
      the 10-year period between January 1987 and December 1996. Based on the
      assumption that rotaviruses with an identical electropherotype possess the same G
      serotype, the G serotypes of 488 rotavirus-positive specimens that were
      classified into 63 electropherotypes were determined by enzyme-linked
      immunosorbent assay with a supplementary use of G typing by reverse transcription
      PCR. The relative frequencies over the 10-year period were 77.0 (G1), 14.5 (G2),
      2.7 (G3) and 5.3% (G4), leaving the possibility that only 0.4% had G serotypes
      uncommon to human rotaviruses. Of 24,050 rotaviruses extracted by reviewing 63
      serotyping studies in literature, the relative frequencies of the four major G
      serotypes were 50.6 (G1), 9.3 (G2), 7.2 (G3) and 11.6% (G4). As to uncommon G
      serotypes, only 0.9% were described as serotypes other than G1-4, and our
      estimate for potential uncommon serotypes were at most 8.1%. Thus, both this long
      term study focusing on the rotaviruses only from severe cases in a single
      hospital in Japan and the global review of G serotypes published to date indicate
      that the primary target of any rotavirus vaccines should be rotaviruses
      possessing serotypes G1-4.

PMID- 10941934
TI  - Interleukin-8 secretion of human epithelial and monocytic cell lines induced by
      middle ear pathogens.
AB  - Otitis media with effusion (OME) is one of the most common diseases in children.
      Alloiococcus otitidis, a new gram-positive bacterial species, was isolated from
      the middle ear fluid of children with OME; however, the pathogenic role of this
      bacteria is yet unknown. In this study, the ability of cultured epithelial cell
      lines (Hep-2 and Hela) and monocytic cell lines (THP-1 and U 937) to secrete
      chemokine interleukin-8 (IL-8) in response to the A. otitidis organism and three
      bacterial organisms mainly detected from middle ear fluid in OME, and bacterial
      cell components was investigated. When stimulated with four viable bacterial
      cells, epithelial cells and monocytes secreted IL-8 in a time-dependent manner.
      The monocytes produced significantly higher levels of IL-8 than the epithelial
      cells. Compared with that by viable bacterial cells, IL-8 secretion by stimulated
      epithelial cells and monocytes was reduced when the bacteria were heated and
      treated with glutaraldehyde. With bacterial stimulations, cell treatment of
      interferon-gamma caused monocytes to increase the induction of IL-8 production,
      however, the induction of monocyte differentiation caused monocytes to reduce the
      induction of IL-8 production. Furthermore, epithelial cells and monocytes
      stimulated by four viable bacterial organisms physically separated from cultured
      cells reduced the induction of IL-8 compared with directly stimulated cells, and
      monocytes stimulated with soluble extracts prepared from A. otitidis organisms
      produced IL-8 in a dose-dependent manner. These results suggest that part of the
      IL-8 stimulation of the A. otitidis organism may exist in a diffusable factor
      released by the bacteria or soluble components of the bacteria itself.

PMID- 10941935
TI  - Sensitive enzyme-linked immunosorbent assays for the detection of bacterial
      superantigens and antibodies against them in human plasma.
AB  - Enzyme-linked immunosorbent assays for the quantitation of bacterial
      superantigens, staphylococcal enterotoxins A, B and C, toxic-shock syndrome toxin
      1 and streptococcal pyrogenic exotoxin A, were developed. The assays had
      sensitivity to quantitate these toxins to 1.4, 5.9, 16.3, 2.5 and 4.3 pg/ml,
      respectively, in a buffer including 50% human plasma. It takes only 150 min to
      complete the assays after plate preparation. Specificity of the assays agreed
      with those of reverse latex agglutination assay. We also developed enzyme-linked
      immunosorbent assays to detect antibodies against these five superantigens. The
      assays are expected to be significant tools for the study of superantigens in
      several diseases.

PMID- 10941936
TI  - Genetic analysis of the ycgJ-metB-cysK-ygaG operon negatively regulated by the
      VirR/VirS system in Clostridium perfringens.
AB  - The 5'-flanking region of the metB-cysK-ygaG operon, whose expression is
      negatively regulated by the VirR/VirS system in C. perfringens, was analyzed. The
      region contained the ycgJ, mscL, and colA genes encoding a hypothetical protein,
      a large conductance mechanosensitive channel protein, and kappa-toxin
      (collagenase), respectively. Northern analysis revealed that the ycgJ gene was
      transcribed as a 4.9-kb operon together with the metB-cysK-ygaG genes and that
      this operon was negatively regulated by the VirR/VirS system. It is indicated
      that the pfoA (theta-toxin or perfringolysin O), colA, and ycgJ-metB-cysK-ygaG
      genes that belong to the VirR/VirS regulon are situated very close together in a
      26.5-kb region of the chromosome, but do not form a pathogenic island.

PMID- 10941937
TI  - Expression of fimbriae and hemagglutination activity in Shigella boydii.
AB  - This report describes the presence of type 1 fimbriae on Shigella boydii 5 which
      agglutinate guinea pig erythrocytes and feature mannose-sensitive adherence.
      Morphologically, the fimbriae were thin, rigid cylinders 2-5 microm in length and
      35 nm in diameter, and the organella retained axial holes. This is the first
      study to have revealed the existence of type 1 fimbriae on S. boydii.

PMID- 10941938
TI  - Characterization of monoclonal antibodies against Hokkaido strain tick-borne
      encephalitis virus.
AB  - A tick-borne encephalitis (TBE) patient was found in Hokkaido in 1993, and TBE
      viruses were isolated from animals and ticks in our previous studies. To develop
      a diagnostic reagent to identify TBE viruses, monoclonal antibodies (Mabs) were
      produced against the TBE virus strain Hokkaido (Oshima 5-10). Seven Mabs were
      obtained which reacted with the envelope protein of the Oshima 5-10 strain. These
      Mabs were flavivirus genus-specific, TBE virus complex-specific or TBE virus type
      specific. The Mabs are applicable for identification of TBE virus strains.

PMID- 10941939
TI  - Mumps virus can suppress the effective augmentation of HPC-induced apoptosis by
      IFN-gamma through disruption of IFN signaling in U937 cells.
AB  - Cells of the human promonocytic cell line U937 were found to be sensitive to
      hexadecylphosphocholine (HPC), which is a potential anticancer drug. Induction of
      apoptosis was found in U937 cells after treatment with HPC for 24 to 48 hr. The
      apoptosis in U937 cells exposed to HPC was increased significantly in the
      presence of interferon-gamma (IFN-gamma). The augmentation of HPC-induced
      apoptosis by IFN-gamma is repressed in cells (U937-MP) persistently infected with
      mumps virus. A persistently infected cell line, U937-MP, showed poor induction of
      signal transducers and activators of transcription-1alpha (STAT-alpha), STAT-2,
      p48 and IFN-regulatory factor-1 (IRF-1), which are closely correlated with
      interferon-alpha (IFN-alpha) and IFN-gamma signaling pathways. Expression of MHC
      class-I or class-II was augmented by IFN-alpha or IFN-gamma in U937 cells, but
      not in persistently infected cells. Therefore, it is suggested that the IFN-gamma
      signaling pathway plays an important role in the augmentation of HPC-induced
      apoptosis. Mumps virus can suppress the IFN-gamma signaling pathway and
      subsequent development of apoptosis.

PMID- 10941940
TI  - Hepatitis C virus NS5B RNA replicase specifically binds ribosomes.
AB  - Hepatitis C virus (HCV) non-structural protein 5B (NS5B) is an RNA replicase. We
      expressed full-length NS5B (591 amino acid residues) in Escherichia coli as a
      fusion protein with maltose binding protein (MBP-NS5B). MBP-NS5B was recovered in
      the soluble fraction after centrifugation at 40,000 x g and affinity-purified
      with amylose resin. The purified MBP-NS5B had a high-level of poly (A), oligo (U)
      dependent UMP incorporation with a Km of 2 microM for UTP. Surprisingly, the
      enzymatically active MBP-NS5B was sedimented by ultracentrifugation at 160,000 x
      g. The pellet contained 16S and 23S ribosomal RNAs, suggesting that ribosomes
      were associated with MBP-NS5B. Ribosomes and MBP-NS5B were subsequently co
      purified on amylose resin. Deletion study revealed that either the N-terminal
      (amino acid residues 1-107) or the C-terminal (amino acid residues 498-591)
      region of NS5B were sufficient for this association with ribosomes. We further
      found that NS5B also bound with human ribosomes. Our results implicate a novel
      mechanism of coupling between replication and translation of the viral genome in
      the life cycle of HCV.

PMID- 10941941
TI  - Cardiology services after stress testing: are there sex differences? A population
      based study.
AB  - To test the hypothesis that, in a population-based cohort of persons undergoing
      stress tests, female sex was negatively associated with the use of cardiology
      visits in persons with no documented coronary artery disease (CAD) but that this
      association did not exist when CAD was established. Sex differences in the use of
      invasive cardiac procedures have been clearly documented, but data on physician
      encounters, an integral part of care, are lacking. A population-based cohort
      consisting of all Olmsted County, Minnesota residents who underwent an initial
      stress test in 1987, 1988, and 1989 in Olmsted County was examined. Medical
      records were reviewed for baseline characteristics including CAD diagnosis
      status, test results, and cardiology visits in the year following the stress
      test. Regression models were constructed to determine whether sex is
      independently associated with the probability of a visit. In the year after
      stress testing, there was no difference between the sexes in the use of inpatient
      (OR for female sex 0.88, 95% CI 0.62-0.97, P = 0.365) and outpatient/consultative
      (OR for female sex 1.24, 95% CI 0.95-1.61, P = 0.6) cardiology visits. Women
      were, however, less likely to receive preventive cardiology visits (OR for female
      sex 0.77, 95% CI 0.62-0.97, P = 0.02). This was largely related to less use of
      preventive visits among older women with documented coronary artery disease
      (CAD). In the absence of documented CAD, when the stress test was positive, women
      were less likely to receive preventive visits. In this geographically defined
      population within one year after an initial stress test, there was no sex
      difference in the use of in-patient or out-patient visits but women were less
      likely to receive preventive cardiology visits in the year after stress testing.
      Further studies are needed to understand the reasons for and impact of these care
      patterns.

PMID- 10941942
TI  - Where do developing World clinicians obtain evidence for practice: a case study
      on pneumonia.
AB  - There are few data on the practice of evidence based medicine in the developing
      world, nor on the actual sources of evidence that clinicians use in practice. To
      test the hypothesis that there was variation between and within developing
      countries in the proposed management of a patient with hospital acquired
      pneumonia, and that part of the variation can be explained by the sources of
      evidence used. Questionnaire responses to hypothetical case history.
      Investigators from 6 centres within the International Clinical Epidemiology
      Network (INCLEN) in China, Thailand, India, Egypt, and Kenya. Doctors chosen to
      represent primary and secondary hospital practice in the regions of the study
      centres. Investigations and initial treatments which would be ordered for a
      hypothetical 60-year-old woman who develops pneumonia 5 days after hospital
      admission, whether local data on antibiotic sensitivities are available and where
      information would be obtained to guide management. Chest x-ray and sputum gram
      stain/culture were consistently the most commonly ordered investigations, there
      being much greater variation in the initial treatment choices with either
      penicillin, a third-generation cephalosporin or aminoglycoside being the most
      popular choice. Textbooks were the commonest form of information source, and
      access to a library, textbooks and journals were statistically significantly
      associated with appropriate choice of investigations, but not treatment. Access
      to local antibiotic sensitivities was associated with appropriate initial
      treatment choice. Improving access to information in the literature and to local
      data may increase the practice of evidence-based medicine in the developing
      world.

PMID- 10941943
TI  - Intravesical chemotherapy prophylaxis in primary superficial bladder cancer: a
      meta-analysis of 3703 patients from 11 randomized trials.
AB  - The impact of intravesical chemotherapy prophylaxis on recurrence of superficial
      transitional cell carcinoma of the bladder is poorly defined. The objective of
      this report is to present a meta-analysis of the available clinical trial data to
      quantify the effect of intravesical chemotherapy on tumor recurrence following
      complete transurethral resection (TURB) in patients with newly diagnosed
      superficial bladder cancer. A prospective protocol outlining the above meta
      analysis was initially developed followed by a thorough search of the existing
      published literature using strict eligibility criteria. Eleven randomized trials
      were found that met protocol specifications. These studies contained data on 3703
      patients that were statistically combined using a fixed effects model (Peto). The
      outcome of interest was the proportion of patients recurring at 1, 2, and 3 years
      post-TURB. Combining all 11 studies using 1-year recurrence as the outcome
      measure yielded a Peto odds ratio (ORp) of 0.56, demonstrating a 44% reduction in
      1-year recurrence among patients treated with intravesical chemotherapy versus
      those treated with TURB alone. A statistical test for heterogeneity (Q) showed
      these data to be heterogenous (the studies are not measuring an effect of the
      same size). Sensitivity analyses were performed to determine sources of
      heterogeneity. These tests suggest that chemotherapy treatment schedule may
      account for the wide variation in tumor recurrence rates across studies. When the
      available clinical trial data were stratified by duration of treatment, the meta
      analysis showed that intravesical chemotherapy decreased tumor recurrence from
      30% to 80% depending on the outcome of interest (i.e., recurrence at 1, 2, or 3
      years post-TURB). Intravesical chemotherapy appears to have a major impact on
      decreasing the chance of recurrence of superficial transitional cell carcinoma of
      the bladder. This is in contrast to prior analyses suggesting only modest
      efficacy in this clinical setting (i.e., on the order of a 14% reduction in
      recurrence).

PMID- 10941944
TI  - Health care seeking behavior following a health survey: impact on prevalence
      estimates of chronic diseases.
AB  - This article addresses the time sequence between a population health survey and
      subsequent health care use and how this changes the incidence estimates of
      selected chronic diseases. A cardiovascular survey of a representative sample of
      the adult population of Manitoba, Canada was linked with the health insurance
      claims database. Of the 2792 subjects in the survey, 98% were linked
      successfully, using an encrypted personal health insurance number. Five years of
      physician claims data for the survey participants were reviewed including 18
      months prior to and 42 months following the survey. Survey participants started
      seeking confirmation of possible hypertension as soon as they received blood
      pressure information at the interview. Confirmation of diabetes and elevated
      cholesterol were not completed until 3-4 months after participants had received
      the laboratory test results. As many as 4.6 times more new cases of hypertension
      per month, 5.1 times more cases of elevated cholesterol, and 3.3 times more cases
      of diabetes were diagnosed following the survey. Surveys designed to determine
      the prevalence of specific chronic diseases generate new cases within a short
      time afterwards, thus affecting the original prevalence estimates. The process of
      assessing the burden of disease in a population is dynamic rather than static,
      and comparisons across populations need to take into account the frequency and
      recency of past surveys.

PMID- 10941945
TI  - The cost diary: a method to measure direct and indirect costs in cost
      effectiveness research.
AB  - From a societal perspective long-term clinical trials or follow-up studies should
      preferably not only include an evaluation of the health effect for the patient,
      but also an economic evaluation. In order to yield comprehensive medical and
      nonmedical resource use data, we at least partly depend on respondents' recall
      for collecting these costing data. A patient cost diary was developed in order to
      estimate total resource use, expenses, and lost production due to illness and
      treatment. We applied the cost diary in two randomized clinical trials evaluating
      the cost-effectiveness of behavioral rehabilitation in 205 fibromyalgia and
      chronic low back pain patients. The use of the diary was evaluated, studying the
      feasibility, the influence of the period of data collection on the results, and
      some aspects of validity. Eighty-five percent of the patients completed at least
      one diary and in total 68% of the diaries were returned. Although the results for
      the three alternative periods of data collection (keeping the diary 1 week every
      month, 2 weeks every 2 months, or a full year) were not significantly different,
      they were only moderately correlated. Finally, self-reported specialist care
      contacts were generally in agreement with data from an insurance company.
      However, for physiotherapy contacts there were differences between the self
      reported and insurance data. This study shows how the cost diary might be used
      successfully in cost-effectiveness studies.

PMID- 10941946
TI  - Occurrence and risk factors of oral candidiasis treated with oral antifungals in
      seniors using inhaled steroids.
AB  - Oral candidiasis (OC) is a frequent side effect of inhaled corticosteroids
      (iCSTs). This study estimated occurrence and significance of risk factors of OC
      treated with antifungals in users of iCSTs under conditions of normal use. This
      retrospective analysis used data drawn from drug insurance plan records in
      Quebec, Canada. The sample contained 27,000 seniors using anti-asthma medications
      during 1990. Three years of data (1989-1991) were searched for use of oral
      antifungals concurrent with exposure to iCSTs. A case-control study examined
      factors leading to increased probability of first incidence of OC in new users of
      iCSTs. Three-year occurrence for OC was 7%. Increased risk for a first occurrence
      of OC was significantly associated with higher doses of iCST, increased length of
      iCST exposure, use of antibiotics, use of oral steroids, having three or more
      prescribers, a history of use of both high and low strengths of iCST, and
      concurrent use of oral steroids and diabetes medications. The occurrence of OC is
      relatively high. Knowledge of factors leading to increased risk could facilitate
      the targetting of patients who need timely intervention, under conditions of
      normal use.

PMID- 10941947
TI  - An effectiveness trial of a diagnostic test in a busy outpatients department in a
      developing country: issues around allocation concealment and envelope
      randomization.
AB  - Methods to ensure allocation concealment in a randomized controlled trial in a
      busy outpatients department may disrupt usual clinical behavior, and thereby
      modify the effect of a diagnostic test. In a clinical trial of chest radiography
      in ambulatory children, concealment was maintained by means of sealed
      sequentially numbered manila envelopes. Baseline information was collected on all
      potential participants before they were presented to a clinician for a decision
      on inclusion in the trial. Excluded patients were followed up. Of 59 excluded
      patients, only 16 allocation envelopes had been opened or were not accounted for,
      although 12 of these had non-radiograph allocations (P = 0.05). There was no
      difference between patients excluded from radiograph and non-radiograph groups in
      baseline characteristics or primary outcome measure. Most of the improper
      exclusions occurred early in the study; improved monitoring and feedback reduced
      the problem. Sealed opaque sequentially numbered envelopes may be appropriate for
      trials of diagnostic tests in settings where centralized randomization is not
      feasible, and given careful monitoring of the enrollment process.

PMID- 10941948
TI  - Smoking characteristics, antioxidant vitamins, and carotid artery wall thickness
      among life-long smokers.
AB  - We studied the associations between the common carotid-intima-media thickness
      (IMT), as a marker of atherosclerosis, and smoking characteristics and
      antioxidant vitamins among 158 male life-long cardiovascular disease (CVD)-free
      smokers. An "increased" carotid IMT was defined as the upper 25%. The prevalence
      of increased IMT was 2.5 times (odds ratio (OR) = 2.5; 95% CI: 1.1, 5.6) higher
      among smokers inhaling smoke deeply into the lungs than among moderate and non
      inhalers. This association decreased when adjusted for other CVD risk factors.
      Smokers with an increased carotid IMT did not differ significantly in mean
      antioxidant vitamin intake and status with the remaining group. However,
      classical CVD risk factors contributed importantly to increased carotid IMT. In
      our study, depth of inhalation was the only smoking characteristic associated
      with carotid IMT although attenuated after adjustment for traditional risk
      factors for CVD. Furthermore, in these life-long smokers not using any vitamin
      supplements, no associations were found for antioxidant vitamins.

PMID- 10941949
TI  - Assessment of environmental tobacco smoke exposure in children with asthmatic
      symptoms by questionnaire and cotinine concentrations in plasma, saliva, and
      urine.
AB  - To validate a detailed questionnaire for assessment of environmental tobacco
      smoke (ETS) exposure by the biomarker cotinine in various media, a population
      based study in the urban area of Malmo, Sweden was performed in children aged 8
      13 years with and without asthmatic symptoms. There were strong correlations
      between urinary and saliva cotinine concentrations and also, though to a lesser
      extent, between these media and plasma. Even a detailed questionnaire gave only a
      rough picture of the ETS exposure, as indicated by the biomarkers. In a
      multivariate model, the most significant questionnaire-derived predictor of the
      cotinine levels was the maternal smoking habits; other questionnaire variables
      gave only a minimal explained variance. Children with a history of asthmatic
      symptoms had statistically significantly lower median cotinine levels in urine
      and saliva compared to referent children, most likely because of the antismoking
      information to their parents. This should be considered in epidemiological
      studies of ETS risks.

PMID- 10941950
TI  - Analysis of menstrual diary data across the reproductive life span applicability
      of the bipartite model approach and the importance of within-woman variance.
AB  - The nature of variability in menstrual function has not been adequately described
      or quantified across the reproductive life span. This article evaluates the
      applicability of the bipartite model approach to the analysis of menstrual data
      and the relative importance of within-woman variability across the reproductive
      life span using data from the Tremin Trust data, a large prospective study in
      which women maintained menstrual diaries throughout their reproductive life. We
      first consider how the boundaries of the Gaussian portion of the distribution
      change with age, and reflect upon the implications of these distribution changes
      for definitions of normal cycling. We next estimate the change in mean cycle
      length, in between- and within-woman variance and in the probability of having a
      nonstandard cycle across the reproductive life span. Finally, we characterize the
      dynamics of menstrual cycling within women over time at various points in the
      reproductive life span.

PMID- 10941951
TI  - Heroin and opiate emergencies in Vienna: analysis at the municipal ambulance
      service.
AB  - Vienna suffered an epidemic of heroin abuse in recent years, with drug-deaths due
      to opioids increasing from 62 in 1991 to 143 in 1993. The aim of this study was
      to make observations about illicit opioid-use with the ambulance service as a
      data source. From June 1994 to August 1995, the structured run records of the
      ambulance service were reviewed. Those with a presumptive diagnosis of "heroin or
      opiate" overdose were collected, characteristics of emergencies and patients were
      analyzed. The run records demonstrated a large number of non-fatal emergencies
      due to opioids, involving 528 men and 179 women in 1087 emergencies. These
      emergencies were on the average 6.8 times as prevalent as drug-fatalities. A
      group of 189 persons could be identified, who caused 52.2% of all emergencies and
      showed a threefold mortality rate during the observation period. In Vienna, the
      records of the municipal ambulance service provided valuable insights on opioid
      abuse. We suggest local analysis of non-fatal emergencies due to opioids, as this
      might lead to a new source of information on illicit abuse of these drugs.

PMID- 10941952
TI  - Diagnostic performance of biopsy-based methods for determination of Helicobacter
      pylori infection without a reference standard.
AB  - Endoscopic biopsy-based tests are considered to be the reference method for
      diagnosing Helicobacter pylori infection and monitoring antibiotic treatment, but
      unbiased data on their diagnostic performance is lacking. In this study we
      evaluated the diagnostic performance of culture, histology and rapid urease
      testing of antral biopsies separately and in combination. Antral biopsies were
      taken from consecutive patients undergoing upper gastrointestinal endoscopies at
      a single center between January 1995 and May 1997. The biopsies were examined for
      culture, histology, and CLOtest. The diagnostic performance, i.e., the
      sensitivity and specificity of the tests was estimated with 7 non-linear
      equations in 7 unknowns. To determine sources of heterogeneity that may have
      biased the results, data were stratified for age, gender, and whether they were
      taken before or after anti-Helicobacter antibiotic treatment. During the study
      period 631 patients underwent 869 upper gastrointestinal endoscopies. In 122
      (14%) of the antral specimens the test results of culture, histology and CLOtest
      differed. Based on the nonlinear regression techniques we estimated that in 347
      tests (40%) H. pylori infection was present. Overall sensitivity, specificity,
      positive and negative predictive value for each test were as follows: culture
      91.4%, 96.3%, 94.2%, 94.4%, respectively; histology 90.3%, 97.8%, 96.4%, 93.8%,
      respectively; CLOtest 94.9%, 96.7%, 95.0%, 96.6%, respectively. In combination,
      the three tests provided the definitive diagnosis, either non-infected or
      infected, in 862 out of the 869 tests. Sensitivity of gastric antral histology
      was 64.9% (95% CI: 38-86) in females who did and 84.5% (95% CI: 77-90) in females
      who did not have had recent antibiotic therapy to cure the infection.
      Approximately 5-10% of H. pylori infected patients, were mis-diagnosed with a
      single biopsy-based test taken from the gastric antrum. Only a combination of
      bacterial culture, histological examination and the CLOtest represents an
      appropriate reference standard for research purposes to identify infected
      patients.

PMID- 10941953
TI  - European surveillance on Creutzfeldt-Jakob disease: a case-control study for
      medical risk factors.
AB  - Medical risk factors for Creutzfeldt-Jakob disease (CJD) were analyzed in a
      prospective ongoing case-control study based on European CJD surveillance.
      Detailed data on past and recent medical history were analyzed in 405 cases and
      controls matched by sex, age, and hospital. Data were correlated with
      polymorphism at codon 129 of the prion protein gene. Our analysis did not support
      a number of previously reported associations and failed to identify any common
      medical risk factor for CJD. Although not statistically significant, brain
      surgery was associated with an increased risk of CJD. A detailed medical history
      should be obtained in every suspected CJD case in order to identify iatrogenic
      sources of CJD.

PMID- 10941954
TI  - Occurrence of chronic obstructive pulmonary disease among Canadians and sex
      related risk factors.
AB  - The etiology of chronic obstructive pulmonary disease (COPD) has not been fully
      understood. This analysis assessed the prevalence of COPD and its risk factors
      among Canadian men and women. The analysis was based on the data from 7210
      subjects aged 35 to 64 years who participated in the first cycle of National
      Population Health Survey in 1994-1995. COPD was considered present if an
      affirmative response was given to the question: "Do you have chronic bronchitis
      or emphysema diagnosed by a health professional?" In order to take the complex
      survey design into account, analytic weights incorporating a design effect were
      used in all statistical analyses. The prevalence of COPD was 2.1% in nonsmokers,
      2.7% in ex-smokers, and 8.2% in smokers in women. In men, the corresponding
      prevalence was 0.8%, 2.9%, and 3.5%, respectively. The adjusted odds ratio for
      current smoking men and women who started smoking before age of 18 years was 3.0
      and 5.9 compared with their nonsmoking counterparts. Overweight women
      demonstrated a 2.4-fold increase in the prevalence of COPD compared with women
      with normal weight. Men from low-income families had an odds ratio of 3.7
      compared with those from high-income families. A history of allergy was
      significantly related to COPD in both men and women. COPD was common among
      Canadian women. Early initiation of smoking and being overweight had stronger
      relationships to the prevalence of COPD in women than in men. On the contrary,
      household income was more strongly related to COPD for men than for women.

PMID- 10941956
TI  - RDAs hung out to DRI.

PMID- 10941955
TI  - Improving drug treatment in general practice.
AB  - In the international Drug Education Project, an educational program involving
      auditing and feedback in peer groups to improve the treatment of asthma and
      urinary tract infections (UTI) was developed and tested in primary care.
      Individualized feedback was provided and discussed in 24 Dutch peer groups
      showing doctors their prescribing practices and underlying reasons for treatment.
      A parallel, randomized controlled design was used to test the effect on
      competence and actual prescribing; in one study arm doctors received feedback on
      asthma treatment and in the other on UTI treatment. Especially the messages to
      treat asthma exacerbations with oral corticosteroids (17% increase) and to
      prescribe short courses for UTI (decrease duration of 1.8 days) brought about
      large improvements. Both messages concerned acute situations, and were clear and
      relatively easy for GPs to implement. GPs will experience more barriers when
      changing maintenance treatment of an asthma patient, which could explain the more
      limited success of this part of the educational program: the proportion of
      patients treated with inhaled corticosteroids increased 5%. A ceiling effect was
      experienced regarding drug choice for UTI.

PMID- 10941957
TI  - Is our approach to treating chronic hepatitis C all wrong?

PMID- 10941958
TI  - A charter of rights for children, parents and families seen and cared for by
      pediatric gastroenterologists.

PMID- 10941959
TI  - Copper homeostasis in infant nutrition: deficit and excess.

PMID- 10941960
TI  - Hepatitis B vaccination and control of hepatitis B-related liver disease.

PMID- 10941961
TI  - Gastrointestinal response to food: artificial or not?

PMID- 10941962
TI  - A multicenter long-term safety and efficacy trial of preterm formula supplemented
      with long-chain polyunsaturated fatty acids.
AB  - BACKGROUND: The tissue accretion of long-chain polyunsaturated fatty acids is
      compromised in infants born prematurely. Human milk contains long-chain
      polyunsaturated fatty acids, but most preterm infant formulas do not. The long
      term effects of preterm formula supplemented with arachidonic acid and
      docosahexaenoic acid, in proportions typical of those in human milk, were
      therefore investigated. METHODS: In this double-blind, randomized study, 288
      preterm infants received experimental formula (n = 77), unsupplemented (control)
      formula (n = 78), or human milk (n = 133) until 48 weeks postconceptional age
      (PCA). Term formula, without supplemental long-chain polyunsaturated fatty acids,
      was administered from 48 to 92 weeks PCA to formula-fed infants and to infants
      weaned from human milk. Anthropometric and fatty acid data were assessed by using
      analysis of variance. RESULTS: At 92 weeks PCA, no statistically significant
      anthropometric measurement differences were found except for midarm
      circumference, which was smaller in human milk-fed infants than in those fed
      formula. Phospholipid concentrations were similar in the experimental and human
      milk-fed groups, and docosahexaenoic acid levels were significantly greater than
      in the control group. The types and incidences of adverse events were similar
      among the feeding groups. CONCLUSIONS: The results of this study demonstrate the
      efficacy and long-term safety of preterm formula supplemented with long-chain
      polyunsaturated fatty acids.

PMID- 10941963
TI  - Absorption of milk-borne insulin-like growth factor-I into portal blood of
      suckling rats.
AB  - BACKGROUND: Insulin-like growth factors (IGFs) are potent mitogens that have been
      implicated in control of growth and development during the perinatal period.
      These hormones are also present in biologically significant quantities in
      mammalian milks. Although one site of action of these IGFs may be at the
      intestinal level, current information about whether they pass intact into the
      circulation is conflicting. METHODS: To test the hypothesis that milk-borne IGFs
      are absorbed into blood in receptor-active form, suckling rats were given either
      recombinant human (rh)125I-IGF-I or -II (4 x 10(6) counts per minute [cpm]), and
      the activity present in portal and cardiac blood was examined at 5, 10, 20, and
      30 minutes after ingestion for presence of appropriate molecular weight peptides
      in these samples. In selected samples, purified radioactive samples were tested
      for their ability to bind competitively to crude membranes bearing IGF receptors.
      RESULTS: The results of these studies indicate that rh125I-IGF-I is absorbed in
      receptor-active form into the portal circulation and that maximal amounts are
      present 20 to 30 minutes after ingestion. Estimation of the presence of intact
      hormone was made on the basis of the elution profile of samples when run on gel
      chromatography as well as reversed-phase high-performance liquid chromatography.
      Isolated samples from portal blood also bound competitively to placental
      membranes bearing IGF receptors. In contrast, rh125I-IGF-II could not be
      demonstrated in receptor-active form in portal blood. Chromatography showed
      appropriate sized peaks with greater activity in portal than cardiac samples, but
      competitive binding was not appreciated. CONCLUSIONS: It is likely that at least
      milk-borne IGF-I is absorbed intact and may exert effects on liver and other
      peripheral tissues. In addition, this study lends further credence to the
      possibility of an enterohepatic circulation for IGF-I.

PMID- 10941964
TI  - Efficacy of ursodeoxycholic acid in the treatment of primary sclerosing
      cholangitis in children.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to be beneficial in
      reducing disease activity in adult patients with primary sclerosing cholangitis
      (PSC). However, there has been little published regarding PSC in children and no
      studies investigating the efficacy of UDCA as a treatment for PSC. METHODS: This
      retrospective study included 10 children who were found to have the diagnosis of
      PSC during the past 15 years at the Texas Children's Hospital and Herman
      Hospital, both in Houston, Texas. The male:female ratio was 8:2, the median age
      of onset was 12 years (range, 1-17 years), and eight patients had coexistent
      inflammatory bowel disease (IBD; six ulcerative colitis, one Crohn's disease, one
      unspecified). At the time of diagnosis, five patients were asymptomatic, all of
      whom had IBD with elevated liver enzymes and three of whom had hepatomegaly. Nine
      patients were treated with UDCA. The one patient who did not receive UDCA was
      lost to follow-up soon after diagnosis. The mean dose of UDCA was 17 mg/kg with
      the doses ranging from 9 to 37 mg/kg. RESULTS: There were no side effects from
      the medication recorded for any of the patients. These patients showed a
      significant reduction in alkaline phosphatase, alanine aminotransferase,
      aspartate aminotransferase, and gamma-glutamyl transferase at 1, 3, 6, 15, and 20
      months after treatment. CONCLUSIONS: This study demonstrates that children with
      PSC treated with UDCA have significant improvements in liver biochemical indices.
      However, the long-term effect of UDCA on clinical outcome is unknown.

PMID- 10941965
TI  - Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth
      weight infants.
AB  - BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive
      enteral and parenteral nutriture that provides greater daily riboflavin (vitamin
      B2) than does term infant nutriture, and elevated plasma riboflavin develops in
      these infants after birth. The purpose of this study was to measure plasma and
      urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition.
      Our hypothesis was that elevated plasma riboflavin develops in VLBW infants
      because of high daily intake and immature renal riboflavin elimination. METHODS:
      Eighteen clinically healthy VLBW infants received parenteral nutrition and
      preterm infant formula during the first postnatal month. On postnatal days 10 and
      28, the infants received specially prepared riboflavin-free enteral and
      parenteral nutrition for the 24-hour study period. Serial collections of plasma
      were made at time 0 and at 12 and 24 hours. Urine was collected continuously for
      the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin
      concentration. RESULTS: During the 24-hour riboflavin-free study period on
      postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/-
      SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on
      postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and
      urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the
      24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5
      hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin
      elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased
      40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral
      nutrition and preterm infant formula had elevated plasma riboflavin on postnatal
      days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin
      elimination was greater on postnatal day 28 than on postnatal day 10. Plasma
      riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of
      plasma and urine riboflavin in VLBW infants suggests a lower daily intake would
      maintain plasma riboflavin close to normal.

PMID- 10941966
TI  - Liver abnormalities during growth hormone treatment.
AB  - BACKGROUND: Occasional and transient increase in liver enzymes is reported during
      growth hormone (GH) treatment in girls with Turner syndrome (TS). METHODS:
      Retrospectively, the specific role of GH treatment on liver and muscular enzymes
      was evaluated in 78 patients (48 boys; age range 4.0-20.8 years) affected by GH
      deficiency (GHD) who had been treated with GH for at least 1 year (range: 1-15
      years). All patients had normal serum levels of liver and muscular enzymes before
      GH therapy was started. RESULTS: A clinically asymptomatic and mild increase in
      serum transaminase levels was observed in 6 of 78 patients with GHD during GH
      treatment; 3 (3.8%) of the patients showed an isolated, transitory and self
      limiting increase in serum liver transaminase levels which was noticed 6 to 12
      months after GH treatment was started, and normalized spontaneously within 3 to 6
      months, without stopping the therapy. Three additional patients showed a
      transitory mild increase both in aspartate aminotransferase (AST) and creatine
      phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The
      increase in transaminase levels was not related to the brand of GH preparations
      nor to the dosage administered. CONCLUSIONS: A mild, transient, self-limiting
      increase in serum transaminase may occur during GH treatment. Concomitant
      determination of CK serum levels may quickly differentiate muscular from hepatic
      hypertransaminasemia. Except for persistent cases, this condition does not
      generally require further investigations.

PMID- 10941967
TI  - Fatty acid content of plasma lipid fractions, blood lipids, and apolipoproteins
      in children fed milk products containing different quantity and quality of fat.
AB  - BACKGROUND: Differences in fatty acid content of plasma lipid fractions and serum
      lipid concentrations were investigated among young children fed different milk
      diets composed to achieve a recommended saturated fat intake. METHODS: Thirty
      eight healthy children were randomly assigned to one of four feeding groups at 12
      months: 1) low-fat milk (1.0 g/dL cow's milk fat); 2) standard-fat milk (3.5 g/dL
      cow's milk fat); 3) partially vegetable fat milk (3.5 gtat/dL fat; 50% vegetable
      fat: rapeseed oil); and 4) full vegetable-fat milk (3.5 gtat/dL fat; 100%
      vegetable fat: palm, coconut, and soy oil). Plasma fatty acids, blood lipids, and
      apolipoproteins were analyzed at 15 months, and dietary intakes at 12, 15, and 18
      months. RESULTS: There were significantly lower percentage contributions of
      saturated fatty acids in plasma triglycerides in children fed low-fat milk or
      milk with 50% or 100% vegetable fat than in children fed standard-fat milk.
      Plasma polyunsaturated fatty acid levels were significantly higher in children
      fed milks with vegetable fat than in children fed standard-fat milk. Plasma
      saturated and polyunsaturated fatty acids in triglycerides most closely reflected
      dietary intake. Blood lipid concentrations were lower in children fed milk with
      50% vegetable fat. CONCLUSIONS: Children fed milk with 50% or 100% vegetable fat,
      together with high vegetable-fat and low milk-fat dairy products have lower
      percentages of plasma saturated fatty acids and higher percentages of
      polyunsaturated fatty acids than children fed standard- or low-fat milk and dairy
      products.

PMID- 10941969
TI  - Apparent life-threatening events in a neonate with severe lesions of esophagus
      and stomach.

PMID- 10941968
TI  - Artificial formula induces precocious maturation of the small intestine of
      artificially reared suckling rats.
AB  - BACKGROUND: The artificially reared rat model was used successfully to study the
      effect of nutrition during the early postnatal period on growth and development
      of the neonate. Overgrowth and morphologic changes of the gastrointestinal tract
      are known consequences of artificial rearing. The major goal of our study was to
      elucidate whether artificial rearing-enhanced gut development is caused by
      artificial diet or by gastrostomy and the artificial rearing technique itself.
      METHODS: Suckling rats at day 8 of age underwent intragastric cannulation and
      were machine fed either a cow's milk-based artificial rat's milk substitute or
      pooled rat's milk for 4 days. Dam-fed littermates served as a control. RESULTS:
      Body growth did not differ in the three experimental groups. In rats receiving
      rat's milk substitute, small intestinal wet weight was approximately 60% greater
      than in rats fed rat's milk or control rats. Additionally, the entire small
      intestine was approximately 20% longer in the rat's milk substitute group.
      Morphologically, rat's milk substitute-fed pups demonstrated significantly
      greater intestinal villus length and crypt depth compared with rat's milk-fed or
      control rats. Jejunum and midjejunum of the rat's milk and control groups did not
      differ in these parameters. Intestinal sucrase activity of rat's milk substitute
      fed rats was significantly elevated compared with rat's milk-fed rats or control
      animals. CONCLUSIONS: These results indicate that cow's milk-based formula, not
      gastrostomy or artificial feeding technique, is a principal cause of the small
      intestine overgrowth and precocious maturation of some intestinal functions
      observed in artificially reared sucklings.

PMID- 10941970
TI  - Crohn's disease presenting with Henoch-Schonlein purpura.

PMID- 10941971
TI  - Treatment of microvillus inclusion disease by intestinal transplantation.

PMID- 10941972
TI  - Intestinal duplication presenting as spontaneous hemoperitoneum.

PMID- 10941973
TI  - Gastrointestinal autonomic nerve tumor: the youngest case reported in the
      literature.

PMID- 10941974
TI  - Microvillous inclusion disease: an evolving condition.

PMID- 10941975
TI  - Azathioprine-induced lung toxicity and efficacy of cyclosporin A in a young girl
      with type 2 autoimmune hepatitis.

PMID- 10941977
TI  - Allergic colitis presenting in the first day of life: report of three cases.
AB  - Allergic colitis can occur within hours of birth and should be considered in the
      differential diagnosis of any newborn in whom hematochezia develops. This
      diagnosis should be considered after excluding infectious and anatomic disorders
      common to this age group. The diagnosis is supported by the healthy appearance of
      affected infants and specific proctosigmoidoscopic and histopathologic findings.
      Infants with allergic colitis usually respond to withdrawal of the offending
      antigen, by the use of hydrolyzed cow's milk protein formula or more elemental
      formulas, or if the infant has been breast fed, by the strict removal of the
      offending antigen from the breast-feeding mother's diet.

PMID- 10941976
TI  - Non-Hodgkin lymphoma presenting as a solitary rectal polyp.

PMID- 10941978
TI  - An unusual presentation of congenital hypothyroidism: a report of two cases.

PMID- 10941979
TI  - Spontaneous biliary perforation: biloma resembling a small bowel duplication
      cyst.

PMID- 10941980
TI  - Clinical quiz. Necrotizing fascitis.

PMID- 10941981
TI  - Aerophagia as cause of gaseous abdominal distention in a toddler.

PMID- 10941982
TI  - Manifestations of Munchausen syndrome by proxy in pediatric gastroenterology.

PMID- 10941984
TI  - NASPGN and ESPGHAN on the use of cisapride.

PMID- 10941983
TI  - Cisapride guidelines.

PMID- 10941985
TI  - Ranges of psychiatric morbidity in the old and the very old--results from the
      Berlin Aging Study (BASE).
AB  - The purpose of this study was to determine prevalence rates of psychiatric
      morbidity in the elderly, distinguishing different levels of psychiatric caseness
      as compared to the diagnoses of the DSM-III-R. In a cross-sectional population
      based study in Berlin (West), Germany, 516 people aged 70 to 95+ were randomly
      selected from the obligatory city registry (1990-1993) and stratified by age and
      gender (N = 43 men and N = 43 women in each of six 5-year age groups).
      Psychiatric and physical examinations were carried out in an extensive
      standardized assessment. Distinct psychopathological syndromes occurred in 72.7%
      of the elderly (54.6% of the men, 79.1% of the women). A clinically defined
      psychiatric disorder was found in 49.4% of the elderly (95% confidence interval
      43.9%- 54.9%; 36.4% of the men, 54.0% of the women). Excluding insomnia, the
      overall psychiatric morbidity was 40.4% (30.9% m, 43.8% w). Excluding clinical
      diagnoses that were not otherwise specified in the DSM-III-R, the overall
      prevalence of specified DSM-III-R diagnoses was 23.5% (16.3% m, 26.0% w).
      Excluding dementia, which is known to be age-related, the prevalence was 11.3%
      (8.5% m, 12.2% w) and no significant effect between the age groups was seen. A
      considerable proportion of clinically relevant psychiatric morbidity in the
      elderly does not meet the criteria of specified DSM-III-R diagnoses, although
      these cases are in need of care. The data show that the threshold and severity of
      caseness accounts for important differences when overall psychiatric morbidity is
      assessed.

PMID- 10941986
TI  - Quality of life in psychiatry: a systematic contribution to construct validation
      and the development of the integrative assessment tool "modular system for
      quality of life".
AB  - The aim of the present study is to contribute to an ongoing validation process of
      the Quality of Life (QoL) construct in the clinical field by investigating its
      internal structure. Eight (inter)nationally validated questionnaires have been
      analyzed by an integrative approach in a multicenter study. Data has been
      collected in a mentally healthy (n = 479), a depressed (n = 171) and a
      schizophrenic (n = 139) sample. Apart from conventional psychometric criteria a
      similarity structure analysis (SSA) within a facet analytic methodology has been
      applied. A dimensional structure of the resulting integrative questionnaire
      "Modular System for Quality of Life" (MSQoL) could be generated that consists of
      one "G-factor" (life in general) and six specific dimensions (physical health,
      vitality, psychosocial relationships, material resources, affect, leisure time).
      This basic structure represents a core module measured by 47 items which is
      sufficiently valid for all three samples. The empirical structures of healthy,
      depressed and schizophrenic samples fulfill the first law of attitude and share a
      common variance of 95%. In addition, there are four specific modules (demography,
      family, partnership, profession). No specific modules could be identified for the
      psychopathological subgroups. The conclusion can be drawn that QoL is construed
      very similar by all three investigated populations which is the base for
      searching for quantitative differences and profiles. The MSQoL integrates the non
      redundant components of eight QoL-instruments, is psychometrically able to assess
      the basic structure and can be completed within a cumulative research design by
      items specific for a particular setting.

PMID- 10941987
TI  - Eight month follow-up of delinquent adolescents: predictors of short-term
      outcome.
AB  - Clinicians working with young delinquents are concerned with finding methods to
      predict recidivism in these subjects. It has not been investigated yet to what
      extent psychiatric assessment can be of any help in this field. In this study, we
      investigated whether psychiatric assessment can help to predict recidivism in
      already delinquent adolescents. By means of semi-structured psychiatric
      assessment (Child Assessment Schedule), developmental interview of the parents
      and self-report instruments, we assessed the psychiatric status of 72 delinquent
      adolescents, adjudicated before the Juvenile Court of Antwerp (Belgium). A follow
      up of criminal status after eight months was conducted. Self-report
      questionnaires by the subjects did not differentiate recidivists from non
      recidivists, while parent questionnaires did. Through a semi-structured
      interview, we found that a diagnosis of conduct disorder significantly predicts
      recidivism, while subjects with ADHD and substance abuse show a tendency towards
      more recidivism. We were unable, however, due to the small number of subjects
      showing a psychiatric disorder (e. g. ADHD and PTSD) unrelated to conduct
      disorder, to assess the relative contribution of these disorders to the
      recidivism rate. This study found that psychiatric assessment of delinquent
      adolescents could be of help in predicting recidivism. The necessity of gathering
      information from parents and teachers is demonstrated. Future research should
      include a more extensive group of a delinquent adolescent and should focus on the
      effect of therapeutic interventions.

PMID- 10941988
TI  - Suidical ideation in severe depression.
AB  - Suicidal ideation and communication were investigated for 89 suicide victims with
      a primary severe depression and matched controls. The selection of patients was
      based on multiaxial ratings of all hospitalised patients between 1956 and 1969. A
      blind record evaluation was performed, including scores on Beck's Scale for
      Suicidal Ideation and additional items apart from that scale. There was no
      relation between high scores on the Beck's scale and completed suicide. In the
      male group, suicidal ideation "beyond one's own will" was related to suicide.
      Female suicides that had made an attempt showed higher suicidal ideation than
      female suicides who had not. A substantial minority of the women (22%) committed
      suicide without showing any previous intent. Only 5% of the male suicides had
      shown no previous intent to commit suicide.

PMID- 10941989
TI  - Changes of the neurotransmitter serotonin but not of hormones during short time
      music perception.
AB  - We studied the impact of the perception of pleasant and unpleasant music, as
      rated by healthy subjects with a psychometric scale, on the hormones prolactin
      and ACTH. In addition, the neurotransmitter serotonin (5-HT) was studied using
      the platelet model for central neurotransmission of 5-HT. We did not observe any
      significant changes of prolactin and ACTH during the perception of different
      kinds of music. The 5-HT content of platelets, however, was higher during the
      perception of pleasant music as compared to the perception of unpleasant music
      indicating an increased release of 5-HT during unpleasant music (748 ng/10(9)
      platelets vs. 699 ng/10(9) platelets; p<0.014). The difference of the 5-HT level
      was significantly correlated to the score of unpleasantness as rated by the
      subjects. Our data suggest that perception of unpleasant music induces increased
      release and decreased peripheral and possibly also central intracellular content
      of 5-HT.

PMID- 10941990
TI  - Anxiety among Israeli soldiers during the Gulf War.
AB  - The impact of stress was investigated among Israeli soldiers during the Gulf War.
      The study included 40 healthy young adults in active service. Their scores on the
      Hamilton Anxiety Rating Scale were evaluated during the first week of the war.
      Our subjects were divided into two equal sub-groups (N=20); combatants and
      auxiliary personnel. Higher levels of anxiety were found among the combatants.
      Factor analysis revealed three differing factors: arousal symptoms, numbing and
      distraction. We discuss the possible explanations for these differences.

PMID- 10941991
TI  - Abnormal information processing in dementia of Alzheimer type. A study using the
      event-related potential's field.
AB  - Electrical field changes of event-related potentials (ERPs) were investigated in
      26 patients with dementia of Alzheimer's type (DAT) and 12 age-matched normal
      subjects. The patients were assessed with the Clinical Dementia Rating and Mini
      Mental State. Each patient selected had only mild to moderate mental disability.
      Auditory oddball stimulation was presented at 1.5 s intervals and 1,000 Hz for
      the nontarget and 2,000 Hz for the target tones, both at 85 dB. The target tones
      were 20% of all the tones. The reference-independent data (latency, global field
      power: GFP, dissimilarity index: DISS and location of centroids) were obtained
      and analyzed for each ERP component. The momentary electric strength or
      'hilliness' of the ERPs landscape was indicated by GFP. The patients showed
      prolonged latencies and decreased P300 GFP amplitudes and of N100 GFP. These
      findings suggest that the abnormal electrical field of ERP may reflect abnormal
      information processing following the attentional process for target stimuli in
      DAT patients.

PMID- 10941992
TI  - Psychiatric morbidity and comorbidity following accidental man-made traumatic
      events: incidence and risk factors.
AB  - The aims of this study were to examine the incidence and risk factors of major
      depression, bipolar disorder, psychoactive substance use, psychotic and anxiety
      disorders in relation to post-traumatic stress disorders (PTSD) in a study group
      exposed to two different traumatic events, i.e. 128 fire and 55 motor vehicle
      accident victims. Data have been collected 7-9 months after the traumatic event.
      The diagnosis of axis-I diagnoses, other than PTSD, was made according to DSM-III
      R criteria using the Structured Interview according to the DSM-III-R. The
      incidence of new-onset major depression was 13.4%, generalised anxiety disorder
      (GAD) 12.6 %, agoraphobia 10.2% and psychoactive substance use disorders 6%.
      Simple phobia, panic disorder and obsessive compulsive disorder had a much lower
      incidence (< 2.0%). Fifty-one percent of the victims with PTSD had one or more
      additional axis-I diagnoses, major depression (26.2%), agoraphobia (21.0%) and
      generalised anxiety disorder (24.6 %) being the most common. Physical injury was
      the single best predictor for major depression. The best predictors for the
      development of new-onset anxiety disorders, other than PTSD, were: type and
      horror of the trauma, the extent of physical injury, the loss of control during
      the traumatic event, contextual stimuli, younger age and female sex. IN
      CONCLUSION: comorbid disorders, such as depression, GAD and agoraphobia, commonly
      occur within the first few months after man-made accidental traumata. Trauma
      variables, which are known to be related to the development of PTSD, are also
      related to the occurrence of these comorbid disorders.

PMID- 10941993
TI  - Psychiatric disorder and dysfunction in the UK National Survey of Psychiatric
      Morbidity.
AB  - BACKGROUND: Psychiatric symptoms are wide-spread in the general population, but
      have little effect on performance. Deficits in performance and psychiatric
      symptoms may be the end point of processes common to both, or they may be caused
      by quite different factors. In this paper we examine the epidemiological
      distribution of psychiatric symptoms and performance deficits, as indicated by
      difficulties in activities of daily living (ADL). We hypothesised that ADL
      difficulties are partly independent of psychiatric symptoms, and that this is
      reflected in a different demographic distribution. METHOD: The household
      component of the National Surveys of Psychiatric Morbidity was based on a sample
      of around ten thousand subjects selected at random from the population of Great
      Britain. Psychiatric symptoms were elicited by lay interviewers using the revised
      Clinical Interview Schedule. Performance was assessed by asking about
      difficulties experienced in performing seven types of everyday activity. In this
      paper, our chosen variables were overall symptom and ADL deficit scores, and
      these were related to standard demographic variables. RESULTS: There were
      significant differences in the epidemiological distribution of psychiatric
      symptoms and ADL difficulties. In particular, men experienced more ADL
      difficulties at a given symptom level than women. There were also differences in
      relation to social class, employment status, marital status, ethnic group and
      age. CONCLUSIONS: ADL deficits and psychiatric symptoms are related in the
      general population, and this probably represents common factors in their origin.
      However, discrepancies in the social distribution of these phenomena suggest
      there are also aetiological differences. These do not appear to be the result of
      the impact of physical illness on activities of daily living. Our results
      emphasise that ADL difficulties should be studied separately, particularly in
      investigations of treatment seeking.

PMID- 10941994
TI  - Psychiatric admissions at different levels of the national health care services
      and male criminality: the Northern Finland 1966 Birth Cohort study.
AB  - BACKGROUND: It has earlier been suggested that one-third of violent offenders are
      recorded in psychiatric case registers. Our aim was to study whether violent and
      non-violent offenders differ with respect to admissions to any health care
      inpatient service due to psychiatric disorders. METHODS: We used a genetically
      homogeneous, general population database from the Northern Finland 1966 Birth
      Cohort, together with the Finnish Hospital Discharge Register and national crime
      registers. RESULTS: We found that one-third of violent and one-fourth of non
      violent male offenders had at least one hospital admission due to a psychiatric
      disorder before the age of 32. Sixty-five violent criminals - 1.2% of all cohort
      males (n = 5636) - accounted for 14.4% of all psychiatric treatment days. The
      admission rates among both violent and non-violent male offenders were
      significantly higher when compared with males with no criminal history. Among
      violent males, only half (55.5%) of the inpatient hospital days due to
      psychiatric disorders occurred in psychiatric hospitals. The corresponding
      percentages for non-violent criminals and non-criminals were 64.9% and 74.1%,
      respectively. Among the violent offenders, one-third of hospital inpatient days
      occurred in university hospitals or central hospitals, and only 1.9% of them
      occurred in a comprehensive community care system. CONCLUSIONS: Violent
      offenders' admission rates due to a psychiatric diagnosis are high, and they are
      frequently treated at an inappropriate health care level.

PMID- 10941995
TI  - The gender gap in depression reconsidered: the influence of marital and
      employment status on the female/male ratio of treated incidence rates.
AB  - BACKGROUND: The consistently observed predominance of female over male rates in
      depression - in treated as well as in untreated populations - has never been
      satisfactorily explained. Among the many possible biological and psychosocial
      explanations, marital and employment status have not been extensively studied and
      virtually nothing is known about the combined effect of these variables on sex
      differences in depression. A main reason for this lack of knowledge is the
      limited number of cases available in epidemiological studies. METHODS: The
      present paper examines the combined effects of marital and employment status on
      sex differences in depression rates by analysing in-patient admission rates of
      all depressed patients aged 18-67 admitted for the first ever time to the
      Department of Psychiatry of the University of Vienna from a strictly defined
      catchment area over a period of 42 months. Stepwise Poisson regression analyses
      were carried out in order to identify the relative contribution of these
      variables to the variance of first ever in-patient admission rates for
      depression. RESULTS: A total of 2599 depressed patients fulfilled the inclusion
      criteria. When analysed separately, sex, marital status and employment status
      were shown to have distinct influences, with the "not married" carrying a two
      fold higher risk than the married (2:1), and female sex (1.7:1) as well as not
      being employed (1.7:1) showing similar but smaller effects. In the detailed
      combined analysis, marriage was significantly less advantageous for women than
      for men, while sex differences disappeared completely in the widowed group. Also,
      there was no sex difference in the employed divorced; in the employed widowed
      there was even a slight preponderance in men. The highest rates were found in not
      employed divorced women, the lowest in employed married men. CONCLUSION: While in
      patient admissions are certainly selective in relation to epidemiological data,
      the large sample made it possible to perform combined analyses of sex, marital
      status and employment status. It was shown that the statement of a female
      preponderance in depression, which was found for the total sample, is a gross
      oversimplification. If marital and employment status are considered
      simultaneously, the sex differences disappear in some subgroups and in some are
      even reversed. We suggest that the combined influence of marital and employment
      status should be studied in epidemiological studies as well before conclusions
      about the influence of sex on depression rates are drawn.

PMID- 10941996
TI  - Public belief systems about the helpfulness of interventions for depression:
      associations with history of depression and professional help-seeking.
AB  - BACKGROUND: Previous research has found that there are major differences between
      public and professional beliefs about the helpfulness of interventions for
      depression. The public appear to be guided by general belief systems about the
      helpfulness of medical, psychological and lifestyle interventions rather than by
      specific knowledge about what interventions are effective for depression. The
      present paper examines the effect that experiencing depression and receiving
      treatment might have on these beliefs. METHOD: The study involved a postal survey
      of 3109 adults from a region of New South Wales, Australia. Respondents were
      presented with a vignette describing a person with depression. They were asked to
      rate the likely helpfulness of various types of professional and non-professional
      help and of pharmacological and non-pharmacological interventions for the person
      described in the vignette. Respondents also completed the Goldberg Depression
      Scale and were asked whether they had ever had an episode of depression and
      whether they had seen a counsellor or a doctor for it at the time. Structural
      equation modelling was used to investigate the associations of history of
      depression and professional help-seeking with belief systems. RESULTS: A three
      factor model was found to fit the helpfulness ratings, with factors reflecting
      beliefs in medical, psychological and lifestyle interventions. People who had
      sought help for depression were less likely to believe in the helpfulness of
      lifestyle interventions and more likely to believe in medical interventions. As
      well as these general associations with belief systems, having sought help for
      depression had a number of specific associations with beliefs. Controlling for
      general belief systems, those who had sought help were more likely to rate
      antidepressants, holidays, massage and new recreational pursuits as helpful, and
      were less likely to rate ECT and family as helpful. Those who had a history of
      depression but had not sought help were more likely to rate counselling as
      helpful, and less likely to rate family as helpful. Those with current depressive
      symptoms were less likely to rate telephone counselling, family and friends as
      helpful. CONCLUSION: Having sought help for depression is associated with general
      belief systems about the helpfulness of lifestyle and medical interventions and
      also has some associations with specific beliefs that may reflect experiences
      with treatment (e.g. the helpfulness of antidepressants). Those currently
      depressed or with a history of depression are less likely to regard family as
      helpful, possibly due to poorer social support. Generally speaking, having sought
      help is associated with beliefs closer to those of professionals.

PMID- 10941997
TI  - Effect of different recruitment sources on the composition of a bipolar disorder
      case registry.
AB  - BACKGROUND: Conducting research on low-prevalence conditions presents an ongoing
      challenge for clinical and services researchers. Recruitment through health
      professionals versus other forms of self-referral may affect study group
      composition. METHODS: We compared members of a voluntary case registry for
      bipolar disorder who were recruited through a variety of sources including health
      professionals, support groups, an Internet website, and mailings, brochures, and
      other general public relations activities. We also compared the cost of
      recruitment methods. We hypothesized that self-referred registry members would be
      of higher socioeconomic status and less likely to be in treatment compared to
      members recruited through health professionals. RESULTS: Registrants referred
      through the Internet and patient support groups were better educated and more
      likely to be married than other registrants. However, Internet registrants were
      younger, had fewer lifetime hospitalizations and were more likely to be working.
      Nearly all registrants were in treatment with a psychiatrist. Local registrants
      were predominantly recruited through health professionals and public
      presentations. Registrants outside of the local region most often learned about
      the registry from patient support groups and the Internet. Local registrants were
      less likely to be using non-lithium mood stabilizers. Recruitment through public
      relations efforts was the most expensive method of recruitment, and the Internet
      website was the cheapest. CONCLUSIONS: Diverse recruitment methods can expand the
      population available for clinical trials. For services research, the Internet and
      patient support groups are less expensive ways to identify persons served in
      diverse settings and health plans, but these recruitment methods yield a sample
      that is better educated than the remainder of the population. It remains a
      difficult task to identify minorities and persons not in treatment.

PMID- 10941998
TI  - Generality of support sources and psychometric properties of a scale of perceived
      social support in Turkey.
AB  - PURPOSE: The purpose of the study was to check the generality of the structure of
      social support sources as measured by the Multidimensional Scale of Perceived
      Social Support (MSPSS) and to examine the instrument's psychometric properties in
      Turkey. A previous study in Turkey showed that the definitions of support sources
      may differ across cultures and an attempt was made in the present study to
      incorporate definitions to make the scale more meaningful in Turkey. METHOD:
      Three samples (psychiatry, surgery, and normal), each consisting of 50 subjects,
      were selected from a hospital in Turkey. No significant demographic differences
      were present between the samples. Factor analysis, Cronbach's alpha, correlations
      with other validated scales, and group comparisons were used for the analyses.
      RESULTS: The original three support sources (family, friends, significant other)
      were found. However, in this version of the MSPSS the Family and the Significant
      other subscales incorporated definitions more meaningful in our samples. Internal
      consistency was high and correlations with the other scales showed adequate
      validity, particularly for the psychiatry and the surgery samples. The psychiatry
      sample reported the lowest levels of support. CONCLUSION: The generality of
      support sources, with some differing definitions, was supported. The psychometric
      properties of the MSPSS were adequate for it to be used in Turkey. However,
      social support may be especially relevant for groups with psychological/medical
      problems, and support from close people (particularly the family) may be
      especially predictive of health.

PMID- 10941999
TI  - Fifty years of the congress of neurological surgeons: foundations, objectives,
      and legacies.
AB  - As the Congress of Neurological Surgeons (CNS) approaches its 50th anniversary,
      we review the genesis of our professional society, the environment in which it
      was created, and the legacies it has established. The CNS was the first
      nonexclusive, international neurosurgical organization with no ostensible
      limitations to membership. From its unpretentious origins, the CNS has grown
      remarkably in size and scope, yet it has remained focused on its original primary
      objectives: education, the young neurosurgeon, membership, and volunteerism for
      the benefit of our specialty. During its 50-year history, the CNS has established
      a number of lasting legacies that have positively influenced the development and
      maturation of our chosen specialty. Neurosurgery is unique in having benefited
      from two strong national member organizations to ensure representation of
      different generations and perspectives for policy-making, to provide for two
      comprehensive annual meetings and complimentary journals, to broaden the
      representation for neurosurgery in our interaction with outside agencies, and to
      minimize the cost of services provided on behalf of neurosurgeons.

PMID- 10942000
TI  - Stereotactic radiosurgery in the treatment of metastatic disease to the brain.
AB  - OBJECTIVE: In recent years, stereotactic radiosurgery has been growing in
      popularity as a treatment modality for metastatic disease to the brain. The
      technique has advantages of reduced cost and low morbidity compared with open
      surgical treatment. Furthermore, it avoids the potential cognitive side effects
      of fractionated whole-brain radiotherapy. We undertook this study to determine
      the usefulness of adjuvant radiation therapy and to determine prognostic factors
      in patients treated with stereotactic radiosurgery. METHODS: We reviewed our
      series of patients with metastatic tumors treated using gamma knife stereotactic
      radiosurgery from August 1994 to February 1999. Nonparametric methods were used
      to compare treatment subgroups by demographic features including age, Karnofsky
      Performance Scale score, diagnosis, and systemic disease status. Univariate and
      multivariate analyses of survival and freedom from progression were performed
      using Kaplan-Meier and Cox proportional hazards regression techniques. RESULTS:
      This study included 190 patients harboring 431 lesions who were treated in 263
      treatment sessions. The median follow-up after radiosurgery was 36 weeks for all
      patients. The median actuarial survival from the time of radiosurgery in all
      patients was 34 weeks. When patients were stratified according to tumor
      histology, those without melanoma had a median survival of 39 weeks, and those
      with melanoma had a median survival of 28 weeks. The cause of death could be
      determined in 122 (92%) of the patients known to have died during the data
      capture period. For patients harboring melanoma, death was attributable to
      systemic disease in 31 (47%), to central nervous system-related processes in 29
      (44%), and to unknown causes in 6 (9%). For non-melanoma patients, death was
      attributable to systemic disease in 45 (68%), to central nervous system-related
      processes in 17 (26%), and to unknown causes in 4 (6%). Significantly improved
      survival (P = 0.002) was observed in patients with controlled systemic disease.
      No significant difference in survival could be ascertained for patients
      presenting with up to four lesions, although patients with a total tumor volume
      greater than 9 cc had shortened survival. No survival benefit could be
      demonstrated for whole-brain radiotherapy administered either concomitantly or
      after radiosurgery. CONCLUSION: Factors correlated with significantly improved
      survival included controlled systemic disease and non-melanoma histology. We
      found no significant survival benefit that could be discerned from adjuvant whole
      brain radiotherapy in this patient group.

PMID- 10942001
TI  - Comparison of anatomic and neurophysiological methods for subthalamic nucleus
      targeting.
AB  - OBJECTIVE: The subthalamic nucleus (STN) has recently become the surgical target
      of choice for the treatment of medically refractory idiopathic Parkinson's
      disease. A number of anatomic and physiological targeting methods have been used
      to localize the STN. We retrospectively reviewed the various anatomic targeting
      methods and compared them with the final physiological target in 15 patients who
      underwent simultaneous bilateral STN implantation of deep brain stimulators.
      METHODS: The x, y, and z coordinates of our localizing techniques were analyzed
      for 30 STN targets. Our final targets, as determined by single-cell
      microelectrode recording, were compared with the following: 1) targets selected
      on coronal magnetic resonance inversion recovery and T2-weighted imaging
      sequences, 2) the center of the STN on a digitized scaled Schaltenbrand-Wahren
      stereotactic atlas, 3) targeting based on a point 13 mm lateral, 4 mm posterior,
      and 5 mm inferior to the midcommissural point, and 4) a composite target based on
      the above methods. RESULTS: All anatomic methods yielded targets that were
      statistically significantly different (P < 0.001) from the final physiological
      targets. The average distance error between the final physiological targets and
      the magnetic resonance imaging-derived targets was 2.6 +/- 1.3 mm (mean +/-
      standard deviation), 1.7 +/- 1.1 mm for the atlas-based method, 1.5 +/- 0.8 mm
      for the indirect midcommissural method, and 1.3 +/- 1.1 mm for the composite
      method. Once the final microelectrode-refined target was determined on the first
      side, the final target for the contralateral side was 1.3 +/- 1.2 mm away from
      its mirror image. CONCLUSION: Although all anatomic targeting methods provide
      accurate STN localization, a combination of the three methods offers the best
      correlation with the final physiological target. In our experience, direct
      magnetic resonance targeting was the least accurate method.

PMID- 10942002
TI  - Predictors in the treatment of difficult-to-control seizures by electrical
      stimulation of the centromedian thalamic nucleus.
AB  - OBJECTIVE: To evaluate the efficacy of chronic electrical stimulation of
      centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control
      seizures. METHODS: Thirteen patients underwent ESCM for periods ranging from 12
      to 94 months (mean, 41.2 mo) with electrodes stereotactically placed in both
      centromedian nuclei and connected to internalized stimulation systems. Electrode
      placement was guided by ventriculography and confirmed with magnetic resonance
      imaging before stimulation systems were internalized. Anatomic and
      electrophysiological confirmation of the electrodes' position was accomplished by
      plotting electrode position on anatomic sections of Schaltenbrand and Bailey's
      atlas, and testing cortical recruiting responses and electroencephalogram
      desynchronization elicited by acute low- or high-frequency stimulation,
      respectively. RESULTS: Improvement was highly significant for generalized
      tonicoclonic seizures and atypical absences. Better results were obtained for
      Lennox-Gastaut syndrome. These results were accompanied by a significant decrease
      in generalized spike-wave and secondary synchronous discharges, as well as focal
      spikes in the frontal regions. In contrast, ESCM reduced neither complex partial
      seizures nor focal spikes in temporal regions. Outcomes using ESCM for
      generalized epilepsy were better in patients in whom anatomic and
      electrophysiological confirmation of electrode placement was correct than in
      those in whom the target was missed bilaterally (P < 0.001). The effect was
      sustained during the observation period and was better for longer-term than for
      shorter-term stimulation periods. CONCLUSION: ESCM is an efficient and safe
      procedure for controlling certain seizure types, if patient selection and
      stereotactic placement are satisfactory.

PMID- 10942003
TI  - Cluster analysis of diffusion tensor magnetic resonance images in human head
      injury.
AB  - OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic
      brain injury in humans, and its evolution in the acute phase, remain unresolved.
      This study aimed to characterize the topographical nature of the
      pathophysiological changes in human traumatic brain injury with diffusion tensor
      magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic
      resonance imaging data were acquired from five patients undergoing elective
      ventilation for management of traumatic focal contusion or hematomas. The
      diffusion tensor and the T2-weighted intensity were then computed for every voxel
      in the image data set for each patient. The topographical distribution of
      abnormalities in the trace of the diffusion tensor and T2-weighted images were
      characterized by cluster analysis. RESULTS: In four patients with technically
      satisfactory data, a narrow band of tissue was observed in the periphery of focal
      lesions, which was characterized by selective reduction in the trace of the
      diffusion tensor, without any associated increase in the T2-weighted signal
      intensity. CONCLUSION: This change is interpreted as indicating either a partial
      redistribution of water from the extra- to intracellular compartment, or a
      reduction in the diffusivity of water in the intracellular or cytosolic
      environment. These diffusion and T2-weighted characteristics are also found in
      early ischemic change, hence, such regions may represent potentially salvageable
      tissue at risk of permanent damage. The study illustrates the advantage of using
      information contained within the diffusion tensor in addition to more
      conventional imaging sequences.

PMID- 10942004
TI  - Management of severe traumatic brain injury by decompressive craniectomy.
AB  - OBJECTIVE: The beneficial effect of decompressive craniectomy in the treatment of
      head trauma patients is controversial. The aim of our study was to assess the
      value of unilateral decompressive craniectomy in patients with severe traumatic
      brain injury. METHODS: We retrospectively investigated 49 patients who underwent
      decompressive craniectomy. Intracranial pressure, cerebral perfusion pressure,
      therapy intensity level, and cranial computed tomographic scan features (midline
      shift, visibility of ventricles, gyral pattern, and mesencephalic cisterns) were
      evaluated before and after craniectomy. The gain of intracranial space was
      calculated from cranial computed tomographic scans. Patient outcome was graded
      using the Glasgow Outcome Scale. RESULTS: Thirty-one patients (63.3%) underwent
      rapid surgical decompression within 4.5 +/- 3.8 hours after trauma; in 18
      patients (36.7%), delayed surgical decompression was performed 56.2 +/- 57.0
      hours after injury. Patients younger than 50 years or patients who underwent
      rapid surgical decompression had a significantly better outcome than older
      patients or patients who underwent delayed surgical decompression. Craniectomy
      significantly decreased midline shift and improved visibility of the
      mesencephalic cisterns. The state of the mesencephalic cisterns correlated with
      the distance of the lower border of the craniectomy to the temporal cranial base.
      Alterations in intracranial pressure, cerebral perfusion pressure, and therapy
      intensity level were not significant. The overall mortality of the patients
      corresponded to the reports of the Traumatic Coma Data Bank (1991). CONCLUSION:
      Although there was a significant decrease in midline shift after craniectomy,
      this did not translate into decompressive craniectomy demonstrating a beneficial
      effect on patient outcome.

PMID- 10942005
TI  - Cognitive deficits before treatment among patients with brain tumors.
AB  - OBJECTIVE: There are few data available on the cognitive deficits of patients
      with primary or secondary intracranial mass lesions before treatment. The aim of
      the present study was to document the incidence of cognitive impairments among
      patients with brain tumors of the frontal or temporal lobes, immediately after
      diagnosis but before the commencement of treatment. METHODS: One hundred thirty
      nine patients were neuropsychologically examined using standardized psychometric
      testing procedures that measured various aspects of memory, attention, language,
      and executive functions. Furthermore, reports by the patients of their own
      cognitive functioning in the weeks before treatment were recorded. RESULTS: With
      the classification of test performances below the 10th percentile as impaired,
      more than 90% of patients displayed impairments in at least one area of
      cognition. Impairments of executive functions were observed for 78% of patients,
      and impairments of memory and attention were observed for more than 60% of
      patients. Analysis of the correlation between the patients' own reports and the
      neuropsychological assessment results revealed only a weak relationship. No
      effects of anticonvulsant drugs on cognition were observed. CONCLUSION: The
      present findings suggest that most patients with brain tumors of the frontal or
      temporal lobes demonstrate impairments of cognitive functioning at the time of
      diagnosis. Therefore, for quality assessments of neurosurgical procedures,
      baseline evaluations of cognitive measures should be performed.

PMID- 10942006
TI  - Cerebral hyperperfusion syndrome after percutaneous transluminal stenting of the
      craniocervical arteries.
AB  - OBJECTIVE: Cerebral hyperperfusion syndrome is a recognized complication of
      carotid endarterectomy, with a reported incidence of 0.3 to 1.2%. The incidence
      of cerebral hyperperfusion after endovascular revascularization procedures of the
      craniocervical arteries remains unknown. We evaluated the incidence of cerebral
      hyperperfusion syndrome in our endovascular revascularization series. To our
      knowledge, there are no previous studies evaluating the incidence of
      hyperperfusion syndrome after percutaneous transluminal angioplasty/stenting.
      METHODS: Between March 1996 and February 2000, 140 patients underwent
      percutaneous transluminal angioplasty/stenting of the craniocervical arteries at
      our institution. In all patients, selective bilateral arteriography of the
      carotid and vertebral arteries was performed to document the sites of
      craniocervical stenosis and collateral blood flow and the results of the
      endovascular revascularization procedure. We then reviewed all pertinent medical
      records, arteriographic films, and sectional imaging studies to determine the
      incidence of cerebral hyperperfusion in this series. RESULTS: Seven patients
      (5.0%) developed clinical or radiological manifestations of cerebral
      hyperperfusion. In the target group, percutaneous transluminal stenting achieved
      a 90 to 100% reduction in stenotic lesions (mean stenosis, 91%) of the carotid (n
      = 5) and vertebral (n = 2) arteries. All seven patients remained neurologically
      stable immediately after treatment. There was delayed development of clinical and
      radiographic findings, suggestive of cerebral hyperperfusion. Six patients showed
      evidence of ipsilateral hemispheric edema, including two patients who developed
      intracranial hemorrhage (one parenchymal, one parenchymal and subarachnoid)
      documented by computed tomographic brain scans. Symptoms resolved within 72 hours
      in the four patients without hemorrhage. The two patients with hemorrhage
      recovered during a more protracted period (range, 3 wk to 6 mo). There were no
      long-term sequelae or deaths during a cumulative follow-up of 84 months (mean
      follow-up, 12 mo). CONCLUSION: Hyperperfusion syndrome is an uncommon but
      potentially serious complication of extracranial and intracranial angioplasty and
      stenting procedures. The clinical manifestations are similar to hyperperfusion
      syndrome after carotid endarterectomy; however, the prevalence may be greater in
      the high-risk cohort commonly referred for endovascular treatment. Our findings
      suggest that patients undergoing endovascular stenting procedures should be
      closely monitored for evidence of hyperperfusion, with careful monitoring of
      blood pressure, heart rate, and anticoagulation. Further research is needed to
      confirm that cerebral hyperperfusion is the pathogenesis of this condition.

PMID- 10942007
TI  - Multimodality treatment of nongalenic arteriovenous malformations in pediatric
      patients.
AB  - OBJECTIVE: Previously reported series of arteriovenous malformations (AVMs) in
      pediatric patients have primarily used a single-modality treatment approach of
      either surgery, radiosurgery, or embolization, with significant treatment-related
      morbidity and mortality. At our institution, we have used a combined
      multidisciplinary team approach of all three treatment modalities, alone or in
      combination, to minimize complications and to maximize efficacy in the management
      of these lesions. METHODS: We retrospectively reviewed 40 consecutive pediatric
      patients with AVMs seen at our institution from 1991 to 1999. A multidisciplinary
      team planned the treatment for each AVM. The treatment modality consisted of the
      following approaches: surgery alone in 14 patients, a combination of endovascular
      embolization and surgery in 6 patients, radiosurgery alone in 11 patients, a
      combination of endovascular embolization and radiosurgery in 2 patients, and a
      combination of radiosurgery and surgery in 2 patients. Four patients are
      receiving ongoing multistaged treatment for reduction of the nidus size for
      eventual surgical resection or radiosurgical obliteration of large, complex
      lesions. In one patient, no treatment was recommended. RESULTS: The clinical
      outcomes for the overall series were 95.0% excellent or good (Glasgow Outcome
      Scale score 5 or 4), 2.5% fair (Glasgow Outcome Scale score 3), and 2.5% dead.
      Radiographic efficacy in the patients who have completed treatment was 92.9%
      complete obliteration of their AVMs and 7.1% incomplete obliteration. Of the 10
      patients who had seizures, 9 are seizure-free. CONCLUSION: A combined
      multimodality approach of surgery, radiosurgery, and embolization in managing
      AVMs in pediatric patients can improve outcomes and minimize morbidity and
      mortality.

PMID- 10942008
TI  - Surgical approaches for the treatment of aneurysms on the P2 segment of the
      posterior cerebral artery.
AB  - OBJECTIVE: The P2 segment of the posterior cerebral artery has remained a
      challenging region to expose surgically. We establish a surgical strategy for P2
      segment aneurysms. METHODS: Each segment of the posterior cerebral artery was
      classified according to Zeal and Rhoton's classification. Fourteen of 18 P2
      segment aneurysms were surgically treated. The patient's outcome, the aneurysm
      location, and the surgical procedures were evaluated. A cadaveric study was
      performed to clarify the surgical view obtained via three different surgical
      approaches. RESULTS: Nine aneurysms were clipped, two were trapped, one was
      coated, and one was excised with parent artery reconstruction. Cerebral
      revascularization techniques were used for three patients. The pterional approach
      exposed the anterior half of the P2a segment. The subtemporal approach revealed
      the P2a segment, but its exposure was restricted by its localization in the
      ambient cistern. Via the occipital interhemispheric transtentorial approach, the
      P2p segment was visible and could be manipulated. When the posterior half of P2a
      segment was high on a coronal view of magnetic resonance imaging, it was
      extremely hard to access via any approach. CONCLUSION: A surgical strategy for
      the P2 aneurysm can be planned with accurate prediction of the aneurysm location.
      When the localization of an aneurysm on the posterior half of P2a segment is
      high, a resection of brain tissue may be required.

PMID- 10942009
TI  - Modification of peri-insular hemispherotomy and surgical results.
AB  - OBJECTIVE: We modified the peri-insular hemispherotomy technique devised by
      Villemure and Mascott. Our modified technique and the surgical results obtained
      with this method are presented. METHODS: The frontoparietal operculum is
      resected, and the resection cavity is connected with the lateral ventricle.
      Through this cavity, a transventricular corpus callosotomy and resection of the
      medial temporal structures are performed. RESULTS: This technique was used for 34
      patients, with satisfactory surgical results. Cerebrospinal fluid shunt placement
      was necessary for five patients, and incomplete callosal sectioning was
      postoperatively detected in three cases. CONCLUSION: Our modification of the peri
      insular hemispherotomy can be safely and effectively used to treat epilepsy
      caused by hemispheric lesions, even in cases without ventricular dilation.

PMID- 10942010
TI  - Intraoperative computed tomography for complex craniocervical operations and
      spinal tumor resections.
AB  - OBJECTIVE: To improve intraoperative observation of unexposed anatomic features
      and to verify surgical correction, a mobile computed tomographic (CT) scanner has
      been introduced into the operating room. To date, intraoperative CT scanning has
      been used predominantly for intracranial procedures. We report on the expanded
      use of intraoperative CT scanning for spinal surgery, because CT scanning
      provides excellent observation of osseous pathological features. We report on our
      first 17 cases, which involved complex craniocervical operations and spinal tumor
      resections. METHODS: The Tomoscan M CT scanner (Philips Medical Systems,
      Eindhoven, The Netherlands) is mobile and consists of a translatable gantry, a
      translatable table, and an operator's workstation. In the operating room, the
      patient is placed on the CT table and prepared in the usual manner. The aperture
      of the gantry is covered with sterile plastic drapes. The gantry is docked to the
      table for intraoperative CT scanning as needed for navigation and verification
      during surgery. Each series of scans requires approximately 15 to 20 minutes.
      RESULTS: Our initial experience with neurosurgical spinal cases demonstrated that
      the use of intraoperative CT scanning changed the course of surgery in 6 of 17
      cases. CT scanning was beneficial in facilitating adequate ventral clival and
      craniocervical decompressions, promoting more complete tumor resections, and
      verifying correct graft and instrument placement before surgical closing. Other
      settings in which we have found the mobile CT scanner useful include the
      neurointerventional suite and the intensive care unit; it is also useful for
      radiotherapy planning. CONCLUSION: On the basis of findings for our first 17
      spinal surgery cases, we conclude that intraoperative CT scanning of the spine is
      both feasible and beneficial for select complex spinal procedures from the
      craniocervical junction to the sacrum.

PMID- 10942011
TI  - Navigation-guided opening of the internal auditory canal via the retrosigmoid
      route for acoustic neuroma surgery: cadaveric, radiological, and preliminary
      clinical study.
AB  - OBJECTIVE: We investigated the usefulness of a microscope-based navigational
      system (Multi Koordinaten Manipulator; Zeiss, Oberkochen, Germany) for removal of
      the posterior wall of the internal auditory canal (IAC) via the retrosigmoid
      route. METHODS: A cadaveric study was performed to assess the navigational
      localization error for the retrosigmoid approach to the IAC. Computed tomographic
      findings for 47 acoustic neuroma cases were divided into three groups, on the
      basis of the relationship between the labyrinth and the sigmoid-fundus line
      (medial, on the line, or lateral). Furthermore, the shortest distances between
      the most medial labyrinthine extension and the resection line were measured. In
      20 acoustic neuroma operations, the different features and the practicality of
      the microscope-based navigational system for opening of the IAC were evaluated.
      RESULTS: The mean anatomic localization errors were 0.67 +/- 0.2 mm (95th
      percentile, 1.32 mm) for navigation to the IAC and 0.71 +/- 0.37 mm (95th
      percentile, 1.68 mm) for navigation to the posterior semicircular canal. The
      average distances between the most medial labyrinthine extension and the
      resection line were 3.65, 3.36, and 2.0 mm for the lateral, on-the-line, and
      medial groups, respectively. Direct contouring of structures at risk does not
      take into account the localization error, nor does it provide reliable
      navigational information. A novel indirect contouring concept that takes into
      account the localization error (the safety corridor method) was therefore
      introduced. CONCLUSION: The value of navigational assistance for opening of the
      IAC is promising but still limited. Further development is required before the
      clinical effects of this navigational approach can be evaluated.

PMID- 10942012
TI  - The epidemiology of brain arteriovenous malformations.
AB  - OBJECTIVE: Common estimates of the prevalence rate for pial arteriovenous
      malformations (AVMs) of the brain vary widely, and their accuracy is
      questionable. Our objective was to critically review the original sources from
      which these rates were derived and to establish best estimates for both the
      incidence and prevalence of the disease. METHODS: We reviewed all of the relevant
      original literature: autopsy series, the Cooperative Study of Intracranial
      Aneurysms and Subarachnoid Hemorrhage and related analyses, and other population
      based studies. We also modeled the confidence intervals of estimates for a
      process of low prevalence such as AVMs. RESULTS: Many of the prevalence estimates
      (500-600/100,000 population) were based on autopsy data, a source that is
      inherently biased. Other estimates (140/100,000 population) originated from an
      inappropriate analysis of data from the Cooperative Study. The most reliable
      information comes from a population-based study of Olmsted County, MN, but
      prevalence data specific to AVMs was not found in that study. CONCLUSION: The
      estimates for AVM prevalence that are published in the medical literature are
      unfounded. Because of the rarity of the disease and the existence of asymptomatic
      patients, establishing a true prevalence rate is not feasible. Owing to variation
      in the detection rate of asymptomatic AVMs, the most reliable estimate for the
      occurrence of the disease is the detection rate for symptomatic lesions: 0.94 per
      100,000 person-years (95% confidence interval, 0.57-1.30/100,000 person-years).
      This figure is derived from a single population-based study, but it is supported
      by a reanalysis of other data sources. The prevalence of detected, active (at
      risk) AVM disease is unknown, but it can be inferred from incidence data to be
      lower than 10.3 per 100,000 population.

PMID- 10942013
TI  - Attenuation of brain edema, blood-brain barrier breakdown, and injury volume by
      ifenprodil, a polyamine-site N-methyl-D-aspartate receptor antagonist, after
      experimental traumatic brain injury in rats.
AB  - OBJECTIVE: Traumatic brain injury (TBI) has been shown to induce a significant
      change in polyamine metabolism. Polyamines and polyamine-dependent calcium influx
      play an important role in mediating the effects of excitotoxic amino acids at the
      N-methyl-D-aspartate (NMDA) receptor site. We studied the effects of ifenprodil,
      known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, on
      brain edema formation, blood-brain barrier breakdown, and volume of injury after
      TBI. METHODS: Experimental TBI was induced in Sprague-Dawley rats by a controlled
      cortical impact device, functioning at a velocity of 3 m/s to produce a 2-mm
      deformation. Ifenprodil or saline (10 mg/kg) was injected intraperitoneally
      immediately after the cortical impact injury and then every 90 minutes until 6
      hours after TBI. Blood-brain barrier breakdown was evaluated quantitatively 6
      hours after injury by fluorometric assay of Evans blue extravasation. Brain water
      content, an indicator of brain edema, was measured with the wet-dry method 24
      hours after TBI. Injury volume was quantitated from the brain slices stained with
      2% cresyl violet solution 7 days after TBI. RESULTS: Blood-brain barrier
      breakdown was significantly lower in the traumatic cortex of the ifenprodil
      treated group than in the saline-treated group (84.4 +/- 26.8 microg/g versus
      161.8 +/- 27 microg/g, respectively, P < 0.05). Brain edema was significantly
      reduced in the cortex of the ifenprodil-treated group relative to that in the
      saline-treated group (80.9 +/- 0.5% versus 82.4 +/- 0.6% respectively, P < 0.05).
      Ifenprodil treatment reduced injury volume significantly (14.9 +/- 8.1 mm3 versus
      24.4 +/- 6.7 mm3, P < 0.05). CONCLUSION: The polyamine-site NMDA receptor
      antagonist ifenprodil affords significant neuroprotection in a controlled
      cortical impact brain injury model and may hold promise for the discovery and
      treatment of the mechanism of delayed neurological deficits after TBI.

PMID- 10942014
TI  - Time-dependent astroglial changes after gamma knife radiosurgery in the rat
      forebrain.
AB  - OBJECTIVE: Using an experimental rat model and a clinically relevant treatment
      dose, we performed gamma knife radiosurgery to define the hyperacute radiation
      effects in normal rat forebrain, the time dependence of the astrocytic reaction,
      and the participation of astrocytes in the healing process after single-dose
      gamma radiation injuries. METHODS: Seventy-one rats underwent radiosurgical
      treatment (4-mm collimator) of the caudate-putamen nucleus (single-fraction
      maximal dose of 100 Gy) and were killed at times ranging from 3 hours to 90 days.
      Serial cryostat brain sections were processed with the immunohistochemical avidin
      biotin complex technique, using anti-glial fibrillary acidic protein as the
      primary antibody (to identify astrocytes). RESULTS: Vascular changes, including
      endothelial hyperplasia and vessel wall thickening, were identified as the
      earliest postradiation manifestations and continued throughout the observation
      period. Astrocytes reacted to the radiation injury with hyperplasia and
      hypertrophy. At earlier time points (3-24 h), proliferation was the predominant
      reaction. The expression of glial fibrillary acidic protein in the proliferating
      and hypertrophic astrocytes formed an initial peak in the adjacent corpus
      callosum 3 days after radiosurgery and peaked within the target site between 14
      and 30 days. Astrocytic proliferation and hypertrophy were also observed in
      distant cortices (frontal, parietal, insular, and piriform cortices) and in the
      hippocampus. No necrosis was observed less than 30 days after irradiation. By Day
      90, necrotic lesions with a mean diameter of 4 mm were identified, with glial
      scar at their peripheries. Astrocytic morphological features varied according to
      the distance from the necrosis. The irradiated side contained more glial
      fibrillary acidic protein-containing cells than did the nonirradiated
      contralateral side. CONCLUSION: During the early phase after radiation,
      vasculopathy was the first morphological change and may serve as the initiating
      factor for subsequent changes. Reactive astrocytes appeared not only at the
      target site but also in the surrounding regions; the severity of injury was
      determined by the distance from the target.

PMID- 10942015
TI  - Fiber dissection technique: lateral aspect of the brain.
AB  - OBJECTIVE: The fiber dissection technique involves peeling away the white matter
      tracts of the brain to display its three-dimensional anatomic organization. Early
      anatomists demonstrated many tracts and fasciculi of the brain using this
      technique. The complexities of the preparation of the brain and the execution of
      fiber dissection have led to the neglect of this method, particularly since the
      development of the microtome and histological techniques. Nevertheless, the fiber
      dissection technique is a very relevant and reliable method for neurosurgeons to
      study the details of brain anatomic features. METHODS: Twenty previously frozen,
      formalin-fixed human brains were dissected from the lateral surface to the medial
      surface, using the operating microscope. Each stage of the process is described.
      The primary dissection tools were handmade, thin, wooden spatulas with tips of
      various sizes. RESULTS: We exposed and studied the myelinated fiber bundles of
      the brain and acquired a comprehensive understanding of their configurations and
      locations. CONCLUSION: The complex structures of the brain can be more clearly
      defined and understood when the fiber dissection technique is used. This
      knowledge can be incorporated into the preoperative planning process and applied
      to surgical strategies. Fiber dissection is time-consuming and complex, but it
      greatly adds to our knowledge of brain anatomic features and thus helps improve
      the quality of microneurosurgery. Because other anatomic techniques fail to
      provide a true understanding of the complex internal structures of the brain, the
      reestablishment of fiber dissection of white matter as a standard study method is
      recommended.

PMID- 10942016
TI  - Persistent trigeminal artery: a unique anatomic specimen--analysis and
      therapeutic implications.
AB  - OBJECTIVE: Persistent primitive carotid-basilar artery anastomoses are uncommon,
      and are usually seen on an angiogram or discovered at autopsy. The most frequent
      type of anastomosis is the persistent trigeminal artery. METHODS: A single case
      of a medial variation of the persistent trigeminal artery, as seen in a well
      preserved human adult anatomic specimen injected with red latex, is presented,
      and the anatomy of this uncommon anastomosis is discussed. RESULTS: This specimen
      is unique in its clear preservation of the artery, which arises from the medial
      portion of the right intracavernous carotid artery and gives rise to two
      branches, the inferior hypophyseal artery and the dorsal meningeal artery to the
      clivus. CONCLUSION: A new variation of the persistent trigeminal artery is
      described, which is important to support the possibility that more than one
      variety of carotid-basilar anastomosis exists in this region.

PMID- 10942017
TI  - How many neurosurgeons does it take to write a research article? Authorship
      proliferation in neurosurgical research.
AB  - OBJECTIVE: Authorship proliferation in biomedical research has become rampant;
      the proportion of single-author articles is decreasing, the percentage of
      multiauthor articles is increasing, and the number of authors per publication is
      increasing. To determine whether authorship trends in the North American
      neurosurgical literature parallel trends observed in other areas of the
      biomedical literature, I studied original neurosurgical research articles
      published in the past 50 years. METHODS: I sampled clinical, anatomic, and
      laboratory investigations in Neurosurgery and the Journal of Neurosurgery at 10
      year intervals from 1945 to 1995. For each research article, I determined the
      number of authors, the countries of origin, and the educational degrees of the
      authors. RESULTS: The mean number of authors per article has increased steadily
      in the past 50 years, from 1.8 (standard deviation, +/-0.8) authors per article
      in 1945 to 4.6 (standard deviation, +/-2.1) authors in 1995. The proportion of
      single-author articles is decreasing; these articles accounted for 43% of
      articles in 1945 and only 3% of articles in 1995. Increases in the proportions of
      non-M.D. authors and of articles originating outside the United States were also
      observed. CONCLUSION: The proliferation of multiauthor articles and the decrease
      in the proportion of single-author articles in the neurosurgical literature
      parallel trends observed in many other areas of biomedical research. Possible
      explanations include larger research teams, variable or absent journal criteria
      for defining authorship, and the increased awarding of "gift" authorships.

PMID- 10942018
TI  - Effects of the "special bomb": recollections of a neurosurgeon in Hiroshima,
      August 8-15, 1945.
AB  - This article recountsOFF (Shimada) Kishi's experience when he was appointed as
      chief of the First Investigation Committee that evaluated the damage caused by
      the atom bomb dropped on Hiroshima.

PMID- 10942019
TI  - Osteosarcoma of the temporal fossa with hemorrhagic presentation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Excluding tumors of hematopoietic origin, osteosarcomas
      are the most common bone tumor, although involvement of the brain or cranial base
      is rare. CLINICAL PRESENTATION: A 16-year-old girl with an osteosarcoma of the
      temporal fossa presented with an intracerebral hemorrhage. The management
      strategy of this lesion, including the operative interventions, is described.
      INTERVENTION: Several modes of treatment were undertaken, including radical
      resection of the cranial base lesion and excision of the cavernous sinus after a
      cervical internal carotid artery-to-middle cerebral artery vein bypass graft.
      CONCLUSION: The patient was alive and without evidence of disease 11 months after
      presentation but died shortly thereafter of complications related to adjuvant
      therapies.

PMID- 10942020
TI  - Sporadic unilateral vestibular schwannoma with islets of meningioma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Vestibular schwannomas with meningioma islets have been
      rarely reported in the literature; they have been observed only among patients
      with neurofibromatosis Type II. We present a case of a sporadic mixed tumor in a
      patient without neurofibromatosis Type II that was not suspected before surgery.
      CLINICAL PRESENTATION: A 59-year-old female patient presented with clinical signs
      of progressive loss of hearing. Her family history did not include evidence of
      neurological diseases. Magnetic resonance imaging scans revealed a typical
      unilateral vestibular schwannoma. INTERVENTION: The tumor presented with invasion
      of the surrounding arachnoid membrane, as well as Cranial Nerves VII and VIII.
      Preservation of the facial nerve with complete removal of the tumor was not
      possible. Therefore, Cranial Nerve VII reconstruction was performed. CONCLUSION:
      The concomitant occurrence of schwannomas and meningiomas infiltrating the
      arachnoid membrane might be related to poor clinical outcomes for patients with
      neurofibromatosis Type II, with respect to preservation of facial and acoustic
      nerves. Among sporadic schwannomas, this phenomenon is extremely rare.

PMID- 10942021
TI  - Primary intracerebral Hodgkin's disease mimicking meningioma: case report.
AB  - OBJECTIVE AND IMPORTANCE: A rare case of dura-based primary cerebral Hodgkin's
      disease clinically and radiographically indistinguishable from a meningioma is
      described. CLINICAL PRESENTATION: A 55-year-old immunocompetent woman presented
      with headaches and ataxia. Magnetic resonance images demonstrated a circumscribed
      diffusely enhancing mass with a dural tail attached to the cerebellar tentorium.
      INTERVENTION: Operative inspection also suggested a meningioma, but a frozen
      section of the firm mass revealed an inflammatory lesion. Subsequent pathological
      analysis demonstrated Hodgkin's disease, nodular sclerosing type. An extensive
      workup revealed no systemic disease. CONCLUSION: This case illustrates the rare
      occurrence of primary intracranial Hodgkin's disease and its mimicry of
      meningioma.

PMID- 10942022
TI  - Giant anterior communicating artery aneurysm infiltrated with a primary cerebral
      lymphoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Central nervous system lymphomas exhibit angiotropic
      characteristics. Nevertheless, direct association with an intracranial aneurysm
      is very rarely reported. We present a case of a giant aneurysm infiltrated with a
      large cell non-Hodgkin's lymphoma. The incidence of primary central nervous
      system lymphoma is increasing, and similar cases may become more frequent in the
      future. CLINICAL PRESENTATION: A 65-year-old man had presented with a giant
      anterior cerebral artery aneurysm, new onset of seizures, aphasia, and
      hemiparesis. The aneurysm was treated with Guglielmi detachable coils. Six months
      later, the patient exhibited fever and neurological deterioration. Magnetic
      resonance images suggested an enhancing lesion posterior to the neck of the
      aneurysm. Antibiotic treatment given elsewhere was unsuccessful. INTERVENTION: A
      craniotomy for a suspected abscess was performed, with removal of the aneurysm
      and clipping of the neck. The aneurysm sac appeared to be filled with thrombus
      and pus. The results of aerobic, anaerobic, and fungal cultures were negative.
      Postoperative magnetic resonance images demonstrated a residual mass, posterior
      to the aneurysm within the striatum and the internal capsule. Histological
      examination of the aneurysm wall revealed a large B-cell lymphoma. The diagnosis
      was confirmed by a stereotactic biopsy. Radiation therapy resulted in a transient
      decrease in the size of the lesion. CONCLUSION: Although the tumor was not
      apparent on the initial imaging studies, it may have been the cause of the
      patient's presenting symptoms. Infiltration of the aneurysm wall by the lymphoma
      also raises the possibility of a causal relationship. As the incidence of primary
      central nervous system lymphoma is reported to be on the increase, awareness this
      uncommon association of an aneurysm and malignant lymphoma is of value.

PMID- 10942023
TI  - Fenestration of the posteroinferior cerebellar artery: case report.
AB  - OBJECTIVE AND IMPORTANCE: Fenestrations of cerebral arteries are rare, but very
      important to diagnose given their high association with saccular aneurysms. We
      present the first reported case of a fenestration of the posteroinferior
      cerebellar artery (PICA). CLINICAL PRESENTATION: A 62-year-old man who presented
      with a subarachnoid hemorrhage underwent repeated four-vessel cerebral
      angiography. An isolated right PICA abnormality consistent with a dissection or
      fenestration was revealed. INTERVENTION: The patient underwent surgical
      exploration of his PICA, which confirmed a PICA fenestration without an
      associated saccular aneurysm. The fenestration was wrapped with cotton.
      CONCLUSION: Our case report illustrates the novel anatomic finding of a
      fenestration of the PICA. Knowledge of this entity would be helpful in the
      differential diagnosis of a posterior fossa subarachnoid hemorrhage.

PMID- 10942024
TI  - Inflammatory aneurysm and neurocysticercosis: further evidence for a causal
      relationship? Case report.
AB  - OBJECTIVE AND IMPORTANCE: Two cases of inflammatory aneurysms in patients with
      neurocysticercosis have been reported previously. Clinical and radiographic
      studies suggest a causal relationship. CLINICAL PRESENTATION: A man with
      neurocysticercosis presented with an acute subarachnoid hemorrhage from a left
      middle cerebral artery aneurysm. INTERVENTION: The patient underwent a craniotomy
      and clipping of his aneurysm. Diffuse inflammatory changes and multiple
      cysticercal cysts were found throughout the left sylvian fissure. CONCLUSION: The
      patient had an uneventful recovery. Angiography suggested an inflammatory rather
      than a congenital aneurysm. Although rare, neurocysticercosis may induce aneurysm
      formation in the appropriate setting.

PMID- 10942025
TI  - Pathological laughter as a presenting symptom of massive trigeminal neuromas:
      report of four cases.
AB  - OBJECTIVE AND IMPORTANCE: This is a report of four cases of huge trigeminal
      neuromas that presented with the principle symptom of pathological laughter (PL).
      CLINICAL PRESENTATION: All four patients were male and were in either the third
      or fourth decade of life. In addition to PL, there were neurological deficits
      related to trigeminal nerve, brainstem, and cerebellar dysfunctions.
      INTERVENTION: All tumors were radically excised via a lateral basal temporal
      approach. The PL was cured immediately after surgery. CONCLUSION: PL sometimes
      precedes other neurological manifestations and may be a useful localizing sign.
      The clinical and radiological features in our cases suggest that PL is a result
      of extra-axial compression of the pons and adjoining neural structures.

PMID- 10942026
TI  - Intraarterial recombinant tissue plasminogen activator for ischemic stroke: an
      accelerating dosing regimen.
AB  - OBJECTIVE: Urokinase has been conventionally used for intraarterial thrombolysis
      in acute ischemic stroke. Recently, due to the withdrawal of urokinase from the
      market, attention has been focused on recombinant tissue plasminogen activator (r
      tPA) for intraarterial administration. Data is limited regarding the
      intraarterial dose, efficacy, and safety profile of this agent. METHODS: We
      prospectively studied 8 consecutive patients with acute ischemic stroke who were
      referred for intraarterial lysis. Each patient was considered by the treating
      neurologist to be a poor candidate for intravenous therapy. We administered a
      maximum total dose of 40 mg of r-tPA intraarterially via superselective
      catheterization. Angiograms were obtained after each 10 mg of r-tPA, and
      responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI)
      criteria for perfusion and degree of thrombus. RESULTS: Initial National
      Institutes of Health Stroke Scale (NIHSS) scores ranged from 16 to 21. Intervals
      from presentation to treatment initiation ranged from 1 to 8 hours. After
      administration of r-tPA, neurological improvement (decrease in NIHSS score > or
      =2) was observed in 4 patients. Mean perfusion grade improved from a pretreatment
      score of 0 with increasing doses of r-tPA to 1.1 +/- 1.0 with 10 mg, 1.5 +/- 1.4
      with 20 mg, 2.0 +/- 0.8 with 30 mg, and 2.7 +/- 1.0 with 40 mg. Mean thrombus
      degree decreased from a pretreatment score of 4 with increasing doses of r-tPA to
      2.8 +/- 1.2 after 10 mg, 2.6 +/- 1.4 after 20 mg, 1.9 +/- 1.5 after 30 mg, and
      1.4 +/- 1.5 after 40 mg. Asymptomatic intraparenchymal hemorrhage was observed on
      CT scan in 2 patients at 24 hours. CONCLUSION: Our study suggests that
      intraarterial r-tPA in doses up to 40 mg is relatively safe. The dose appears to
      facilitate the recanalization process by lysis of local thrombus and improvement
      in distal flow.

PMID- 10942027
TI  - Altered baroreflex responses in alpha7 deficient mice.
AB  - The autonomic nervous system controls and coordinates several cardiovascular
      functions, including heart rate, arterial pressure, blood flow and vasomotor
      tone. Neuronal nicotinic acetylcholine receptors (nAChRs) are the interface
      between the nervous system and the cardiovascular system, but it is not known
      which nAChR subtypes regulate autonomic function in vivo. Nicotinic AChRs
      containing the alpha7 subunit are a candidate subtype in autonomic ganglia.
      Stimulation of these nAChRs can increase neurotransmitter release via presynaptic
      mechanisms, as well as mediate fast synaptic transmission via postsynaptic
      mechanisms. To investigate the role of the alpha7 nAChR subunit in cardiac
      autonomic function, we measured baroreflex-mediated responses in alpha7 null
      mice. Here we show that the alpha7 null mice have impaired sympathetic responses
      to vasodilatation, as sodium nitroprusside infusion triggered a 48% heart rate
      increase in wild type mice but only a 21% increase in the alpha7 nulls (P <
      0.001). The mutant mice developed supersensitivity to adrenergic agonists,
      although norepinephrine release from sympathetic nerve terminals could be
      elicited through mechanisms alternative to nAChR stimulation. Baroreflex-mediated
      parasympathetic responses were normal in alpha7 null mice. The decreased
      baroreflex-mediated tachycardia in alpha7 mutant mice indicates that alpha7
      containing nAChRs participate in the autonomic reflex that maintains blood
      pressure homeostasis. The alpha7 mutant mice may serve as a model of baroreflex
      impairment arising from autonomic dysfunction.

PMID- 10942028
TI  - Nicotinic modulation in an animal model of a form of associative learning
      impaired in Alzheimer's disease.
AB  - Eyeblink classical conditioning is a widely used associative learning paradigm
      that has striking behavioral and neurobiological parallels between humans and
      other mammals. Eyeblink conditioning is impaired in older organisms, and patients
      with Alzheimer's disease (AD) are impaired beyond the normal aging deficit. The
      cholinergic system is of demonstrated involvement in eyeblink conditioning.
      Blockade of nicotinic cholinergic receptors with mecamylamine prolonged
      acquisition of conditioned responses (CRs) in young adult rabbits, and the
      nicotinic agonist, GTS-21 ameliorated conditioning deficits in older rabbits.
      Galantamine induces allosteric modulation of nicotinic cholinergic receptors to
      increase acetylcholine release as well as acting as an acetylcholinesterase
      inhibitor. Galantamine doses of 0.0, 1.0, 2.0, 3.0, and 4.0 mg/kg were tested in
      ten daily sessions in 40 retired breeder rabbits (mean age = 29 months) in the
      750 ms delay conditioning paradigm. A dose of 3 mg/kg galantamine was effective
      in improving conditioning in older rabbits, enabling them to achieve learning
      criterion rapidly and to produce a very high percentage of CRs. Control tests of
      rabbits in explicitly unpaired conditions demonstrated that non-associative
      factors could not account for the results. The efficacy of galantamine in a
      learning paradigm that shows severe impairment in AD indicates that the drug may
      be effective as a cognition-enhancer in AD.

PMID- 10942029
TI  - Central nicotinic receptors, neurotrophic factors and neuroprotection.
AB  - The multiple combinations of nAChR subunits identified in central nervous
      structures possess distinct pharmacological and physiological properties. A
      growing number of data have shown that compounds interacting with neuronal nAChRs
      have, both in vivo and in vitro, the potential to be neuroprotective and that
      treatment with nAChR agonists elicit long-lasting improving of cognitive
      performance in a variety of behavioural tests in rats, monkeys and humans.
      Epidemiological and clinical studies suggested also a potential
      neuroprotective/trophic role of (-)-nicotine in neurodegenerative disease, such
      as Alzheimer's and Parkinson's disease. Taken together experimental and clinical
      data largely indicate a neuroprotective/trophic role of nAChR activation
      involving mainly alpha7 and alpha4beta2 nAChR subtypes, as evidenced using
      selective nAChR antagonists, and by potent nAChR agonists recently found
      displaying efficacy and/or larger selective affinities than (-)-nicotine for
      neuronal nAChR subtypes. A neurotrophic factor gene regulation by nAChR
      signalling has been taken into consideration as possible mechanism involved in
      neuroprotective/trophic effects by nAChR activation and has evidenced an
      involvement of the fibroblast growth factor (FGF-2) gene as a target of nAChR
      signalling. These findings suggested that FGF-2 could be involved, according to
      the FGF-2 neurotrophic functions, in nAChR mechanisms mediating the neuronal
      survival, trophism and plasticity.

PMID- 10942030
TI  - Genetic dissection of nicotine-related behaviour: a review of animal studies.
AB  - Nicotine has a broad spectrum of behavioural effects. A considerable body of data
      has emerged indicating genetic factors regulate the behavioural effects of
      nicotine. Experimental genetic techniques have been invaluable in generating
      knowledge on the interrelationship of genetic factors and behavioural
      responsiveness to nicotine. Three different approaches have been invoked to
      explore the relationship of genetic factors to response to nicotine. Firstly, the
      classical genetic tool of inbred lines has been exploited to delineate genetic
      influences in the effects of nicotine. Secondly, the use of selectively bred
      lines has been profitably employed to reveal genetic differences in behavioural
      responses, such as cognition and exploration, to nicotine. These approaches have
      also provided useful information on the contribution of genetic factors
      influencing nicotinic receptors function. Finally the molecular genetic technique
      of gene targetting to create mice with null mutations of specific genes in the
      central nervous system, which is having a tremendous impact in drug addiction
      research, has also been employed to gain insight into the molecular and cellular
      basis of nicotine action. These techniques are proving to be invaluable in
      dissecting the role of different subunits of the nicotinic acetylcholine
      receptors on behaviour. This paper provides a survey of the animal studies that
      have used the above mentioned techniques to gain insight into genetic basis of
      the behavioural effects of nicotine.

PMID- 10942031
TI  - Neuronal nicotinic acetylcholine receptors: from the gene to the disease.
AB  - The neuronal nicotinic acetylcholine receptors are excitatory ligand-gated
      channels. Widely expressed throughout the peripheral and central nervous system,
      their properties depend upon their subunit composition. Furthermore, genetic
      studies have revealed a high degree of variation at the genomic level and
      alternative splicing of the mRNAs coding for these integral membrane proteins. In
      particular, genes coding for alpha4 and alpha7 subunits harbour a high degree of
      polymorphisms. Although well characterised at their molecular and functional
      level, the role of these receptors in the central nervous system remains obscure.
      Despite accumulating evidence for the participation of nicotinic receptors in
      disorders of the central nervous system including nicotinic addiction,
      Parkinson's disease, Alzheimer's disease and Tourette's syndrome, the exact role
      of these receptors is still speculative. Because most of these phenotypes are
      complex and genetically heterogeneous, the investigation is difficult. However,
      in the past few years, significant progress has been made in understanding the
      contribution of nicotinic acetylcholine receptors to the origin of epilepsies and
      schizophrenia. By concentrating on the latest results gained for these diseases,
      we discuss in this review the possible relationships between neuronal nicotinic
      receptors and neurological and psychiatric disorders.

PMID- 10942032
TI  - Genetic and pharmacological strategies identify a behavioral function of neuronal
      nicotinic receptors.
AB  - The studies outlined here used pharmacological and genetic approaches to attempt
      to identify the nicotinic receptors that modulate nicotine-induced seizures. Full
      blown clonic-tonic seizures were induced by intracerebroventricular (i.c.v.)
      injection of nicotine, the alpha4beta2 selective agonist ABT-418 and the alpha7
      selective GTS-21. Cytisine, which is a partial agonist at alpha4beta2-type
      receptors, produced partial seizures. DHbetaE and MLA did not block nicotine
      induced seizures. Instead, both antagonists caused seizures. Restriction fragment
      length polymorphisms (RFLPs) for the alpha7 receptor were identified in two
      inbred strains (C3H and DBA) that differ in sensitivity to nicotine-induced
      seizures. F2 mice derived from a C3H x DBA cross that were homozygous for the C3H
      variant of the alpha7 RFLP were more sensitive to nicotine-induced seizures than
      were F2 mice that were homozygous for the DBA RFLP. In a study that used RI
      strains derived from two selectively bred mouse lines (LS and SS), an association
      between sensitivity to nicotine-induced seizures and an RFLP associated with the
      alpha4 gene was found. These data support the assertion that both alpha4 and
      alpha7 receptor types are involved in modulating convulsions produced by
      nicotine.

PMID- 10942033
TI  - Effects of chronic oral nicotine treatment and its withdrawal on locomotor
      activity and brain monoamines in mice.
AB  - The effects of chronic nicotine and its withdrawal on locomotor activity and
      brain monoamines were studied using a new animal model of administering nicotine
      in the drinking water to male NMRI mice as the sole source of fluid. Locomotor
      activity as well as cerebral concentrations of dopamine (DA), 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine
      (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA) and 3-methoxy-4
      hydroxyphenylethyleneglycol (MOPEG) were measured post mortem on the 50th day of
      nicotine administration or at 12-14 or 23-25 h after withdrawal. On the 50th day
      of drug administration the chronically nicotine-treated mice were more active
      than the control mice drinking tap water and after withdrawal from nicotine the
      locomotor activity dropped to the level of the controls. In chronically nicotine
      treated mice the striatal concentrations of DOPAC, HVA and 5-HIAA, hypothalamic 5
      HIAA and NA as well as cortical NA were elevated. The concentrations of DOPAC,
      HVA and 5-HIAA reversed to control levels within 23-25 h after withdrawal from
      nicotine. The nicotine-induced elevation of the hypothalamic NA concentration was
      still significant at 23-25 h after withdrawal. At 12-14 h after withdrawal the
      hypothalamic concentration of MOPEG was increased. In conclusion, our findings on
      locomotor activity suggest that administration of nicotine in the drinking water
      to mice for several weeks seems to be a relevant method to study nicotine
      dependence. Furthermore, the alterations found in cerebral DA, NA and 5-HT
      metabolism during chronic nicotine administration indicate that all three
      cerebral transmitter monoamines might be involved in nicotine dependence and
      withdrawal.

PMID- 10942034
TI  - The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of
      nicotine dependence.
AB  - A majority of habitual tobacco smokers find it very difficult to quit the habit
      because they become addicted to the nicotine present in tobacco smoke. Nicotine,
      like other psychostimulant drugs of abuse, increases dopamine release in the
      principal terminal field of the mesolimbic system, the nucleus accumbens, and
      there is evidence that this mediates the 'rewarding' properties of the drug,
      which reinforce its self-administration. This review focuses on the working
      hypothesis that addiction to nicotine, and other psychostimulant drugs, depends
      upon their ability to evoke a sustained increase in dopamine release directly
      into the extracellular space which lies between the cells in the nucleus
      accumbens where it stimulates extra-synaptic dopamine receptors. It is suggested
      that increased stimulation of these receptors is associated with increased
      incentive learning or the attribution of increased incentive salience to the cues
      associated with acquisition and delivery of the drug. The hypothesis proposes
      that these cues can become conditioned reinforcers of drug-taking behaviour. The
      receptors, which mediate the effects of nicotine on mesoaccumbens dopamine
      neurones, are desensitised by sustained exposure to nicotine at concentrations
      commonly found in the plasma of habitual smokers. It is proposed that, at times
      when the plasma nicotine concentration is sufficiently high to cause
      desensitisation of the receptors, tobacco smoking is maintained by the
      conditioned reinforcers present in the tobacco smoke. The hypothesis predicts,
      therefore, that conditioned reinforcement may play a more important role in the
      addiction to tobacco than for most other addictive behaviours. As a result,
      studies with nicotine have the potential to contribute to our understanding of
      the neurobiology of addiction which cannot easily be explored using drugs, such
      as cocaine and amphetamine, which invariably increase dopamine overflow in the
      forebrain.

PMID- 10942035
TI  - Nicotinic mechanisms involved in the dopamine activating and reinforcing
      properties of ethanol.
AB  - Ethanol shares with all major dependence producing drugs the ability to activate
      brain mesocorticolimbic dopamine neurons, an important part of the brain reward
      systems. This dopamine activation may be involved in mediating the positive
      reinforcing effects of ethanol. The mechanisms of action of ethanol in its
      activation of this dopamine system remain, however, to be elucidated. A selective
      pharmacological interference with these mechanisms may offer a possibility to
      reduce the reinforcing properties of ethanol without simultaneously interfering
      with the reinforcing properties of natural rewards. Ethanol has been shown to
      directly influence the function of various ligand-gated ion-channels. Several of
      these are located on or nearby mesocorticolimbic dopamine neurons. One such
      receptor is the nicotinic acetylcholine receptor (nAChR). The present article
      reviews a series of investigations aimed at investigating whether nAChRs are
      involved in the dopamine activating and reinforcing properties of ethanol. To
      this end acute and chronic behavioral and neurochemical experiments were
      performed in mice and rats. The results obtained indicate that central nAChRs in
      the ventral tegmental area are involved in mediating the mesolimbic dopamine
      activating and reinforcing effects of ethanol. Furthermore, the ethanol-induced
      activation of these receptors is probably indirect, subsequent to a primary
      interference of ethanol in the nucleus accumbens. Moreover, subchronic nicotine
      treatment enhances the reinforcing and dopamine activating properties of ethanol.
      This long-term effect may, however, derive from autonomic adaptations in response
      to intermittent blockade of peripheral nAChRs (rather than from intermittent
      stimulation of central receptors), and appears to be associated with development
      of a disinhibitory behavior that could involve also other neurotransmitters, e.g.
      serotonin. Taken together, these findings could provide a neurobiological
      explanation to the often observed co-abuse of nicotine and ethanol in man.
      Furthermore, since the behavioral models applied previously have predicted
      therapeutic drug effects in the clinic, the results suggest that selective
      blockade of the ventral tegmental nAChRs that are involved in the above effects
      may provide a new pharmacological alternative in the treatment of alcoholism.

PMID- 10942036
TI  - Role of alpha7 nicotinic receptors in nicotine dependence and implications for
      psychiatric illness.
AB  - It has previously been shown that the reinforcing and dependence-producing
      properties of nicotine depend to a great extent on activation of nicotinic
      receptors within the ventral tegmental area (VTA), i.e. the site of origin of the
      mesolimbocortical dopaminergic projection. Based on the data reviewed in the
      present study, it is suggested that nicotine by stimulating presynaptic alpha7
      nicotinic receptors within the VTA, that are probably localized on glutamatergic
      afferents from the medial prefrontal cortex, produces sequentially an increase in
      glutamate concentrations, stimulation of NMDA receptors found on dopamine (DA)
      containing neurons in the VTA, enhanced firing activity of VTA-DA neurons,
      augmented DA release in the nerve terminal regions, and enhanced c-fos expression
      in the dopaminergic projection areas through activation of D1-DA receptors. In
      addition, it appears that alpha7 nicotinic receptors within the VTA are directly
      involved in nicotine-related reward and withdrawal responses. These data may be
      instrumental in understanding how nicotine interacts with the mesolimbocortical
      dopaminergic system, which is perhaps the most important component of the neural
      mechanisms underlying nicotine dependence. These results may also contribute to
      unraveling the cellular basis of nicotine's association with neuropsychiatric
      disorders, thereby offering the prospect of new therapeutic advances for their
      treatment.

PMID- 10942037
TI  - Rats exhibiting acute behavioural tolerance to nicotine have more [125I]alpha
      bungarotoxin binding sites in brain than rats not exhibiting tolerance.
AB  - Adult male Sprague-Dawley rats trained to discriminate nicotine (0.4 mg/kg, s.c.
      vs vehicle) using a two-lever food-reinforced operant discriminative stimulus
      (DS) paradigm were tested as to the ability of each subject to develop acute
      tolerance to nicotine. Nicotine (0.8 mg/kg, s.c.) was administered to nicotine
      trained rats in their home cage and each rat tested as to its ability to detect a
      2nd dose of nicotine (0.4 mg/kg, s.c.) injected at 30 min intervals thereafter
      (90-180 min). Tolerance was determined by evaluating nicotine-correct responding
      during a 2 min test session. The results of this experiment indicated that 8 out
      of 31 rats (26%) displayed acute tolerance (desensitizers); 18 rats (58%) did not
      exhibit acute tolerance (non-desensitzers) and five rats (16%) fell into a middle
      group and were designated as neither desensitizers or non-desensitizers. The mode
      time for acute tolerance was 150 min, with each desensitizer rat displaying a
      unique temporal profile which was replicable 4-5 weeks later. Receptor
      autoradiographic analysis indicated no significant differences in [3H]epibatidine
      binding sites in the brains of desensitizers and non-desensitizers. In contrast,
      [125I]alpha-bungarotoxin binding was significantly higher in a number of brain
      regions in desensitizers. In situ hybridization analysis revealed no difference
      in alpha7 nAChR subunit mRNA levels between desensitizers and non-desensitizers.
      These observations can be interpreted to suggest that the ability to display
      acute tolerance to nicotine is contingent upon the ability to upregulate alpha7
      nAChRs. These data may also be central to understanding the variability of
      tobacco use in humans, which may be contingent on the ability of the receptors
      binding to alpha-bungarotoxin to be responsive to nicotine-induced
      desensitization.

PMID- 10942038
TI  - Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological
      studies.
AB  - The relationship between smoking and neurological diseases has always been
      controversial. Even the expected association between smoking and increased risk
      for cerebrovascular disease has been debated for years. It was at the end of the
      1980s that smoking became definitively accepted as a risk factor for ischemic
      stroke. More recently, two other neurological diseases have been studied in
      relation to smoking: Parkinson's disease (PD) and Alzheimer's disease (AD). Many
      epidemiological studies have found a highly significant negative association
      between cigarette smoking and these two neurodegenerative disorders. The risk of
      AD or PD in nonsmokers has generally been about twice that of smokers. That is,
      patients with AD or PD are approximately 50% less likely to have smoked
      cigarettes during their lifetime than are age- and gender-matched controls.
      Alternatively, cigarette smokers are 50% less likely to have PD or AD than are
      age- and gender-matched nonsmokers. This statistically significant negative
      association has been interpreted as suggesting that cigarette smoking exerts an
      undefined, biologic, neuroprotective influence against the development of PD and
      AD. A review of all studies that either support or refute this hypothesis is
      presented separately for PD and AD.

PMID- 10942039
TI  - Nicotinic treatment for degenerative neuropsychiatric disorders such as
      Alzheimer's disease and Parkinson's disease.
AB  - Nicotinic systems play an important role in the neural basis of working memory
      and attention. Recent progress in understanding of the structure, function, and
      distribution of central nervous system (CNS) nicotinic receptors and their
      pharmacology has opened up new possibilities for novel CNS therapeutics with
      nicotinic agents. In this paper, we review the theoretical justification and the
      experimental evidence supporting these developments. We focus on the applications
      of nicotinic agonists in CNS disorders that are degenerative in nature, namely
      Parkinson's disease and Alzheimer's disease. We suggest that there is
      considerable potential for therapeutic applications in the near future.
      Clinically, two major issues remain: (a) the selectivity of effects, that is,
      developing compounds which are selective in producing improvement in cognition,
      motor function, attention, or pain without significant side-effects; and (b) the
      realistic likelihood of long-term improvements in everyday functioning in people
      who have degenerative diseases.

PMID- 10942040
TI  - Neuronal nicotinic receptors in synaptic functions in humans and rats:
      physiological and clinical relevance.
AB  - The present report describes the participation of nicotinic receptors (nAChRs) in
      controlling the excitability of local neuronal circuitries in the rat hippocampus
      and in the human cerebral cortex. The patch-clamp technique was used to record
      responses triggered by the non-selective agonist ACh and the alpha7-nAChR
      selective agonist choline in interneurons of human cerebral cortical and rat
      hippocampal slices. Evidence is provided that functional alpha7- and alpha4beta2
      like nAChRs are present on somatodendritic and/or preterminal/terminal regions of
      interneurons in the CA1 field of the rat hippocampus and in the human cerebral
      cortex and that activation of the different nAChR subtypes present in the
      preterminal/terminal areas of the interneurons triggers the tetrodotoxin
      sensitive release of GABA. Modulation by nAChRs of GABAergic transmission, which
      can result either in inhibition or disinhibition of pyramidal neurons, depends
      both on the receptor subtype present in the interneurons and on the agonist
      acting upon these receptors. Not only do alpha7 nAChRs desensitize faster than
      alpha4beta2 nAChRs, but also alpha7 nAChR desensitization induced by ACh lasts
      longer than that induced by choline. These mechanisms, which appear to be
      retained across species, might explain the involvement of nAChRs in cognitive
      functions and in such neurological disorders as Alzheimer's disease and
      schizophrenia.

PMID- 10942041
TI  - Development of ligands for in vivo imaging of cerebral nicotinic receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain functions.
      Findings from postmortem studies and clinical investigations have implicated them
      in the pathophysiology and treatment of Alzheimer's and Parkinson's diseases and
      other CNS disorders (e.g. Tourette's syndrome, epilepsy, nicotine dependence).
      Therefore, it ultimately might be useful to image nAChRs noninvasively for
      diagnosis, for studies on how changes in nAChRs might contribute to cerebral
      disorders, for development of therapies targeted at nAChRs, and to monitor the
      effects of such treatments. To date, only (S)-(-)-nicotine, radiolabeled with
      11C, has been used for external imaging of nAChRs in human subjects. Since this
      radiotracer presents drawbacks, new ligands, with more favorable properties, have
      been synthesized and tested. Three general classes of compounds, namely, nicotine
      and its analogs, epibatidine and related compounds, and 3-pyridyl ether
      compounds, including A-85380, have been evaluated. Analogs of A-85380 appear to
      be the most promising candidates because of their low toxicity and high
      selectivity for the alpha4beta2 subtype of nAChRs.

PMID- 10942042
TI  - Nicotinic acetylcholine receptors during prenatal development and brain pathology
      in human aging.
AB  - Nicotinic acetylcholine receptor (nAChRs) proteins and gene transcripts are
      already present in human prenatal brain and spinal cord at 4-6 weeks gestation,
      and a clear age-related increase in number of nAChRs was apparent during first
      trimester. In pons, there was also a parallel increase in the alpha7 mRNA level
      with age. The highest specific binding of [3H]epibatidine and [3H]cytisine was
      detected in spinal cord, pons and medulla oblongata, and binding of [125I]alpha
      bungarotoxin was highest in spinal cord, medulla oblongata and mesencephalon.
      From the late fetal stage brain nAChRs have been shown to fall with increasing
      age. During aging (between 40 and 100 years) high affinity nicotine binding in
      the frontal cortex decreases in parallel with glutamate NMDA receptor binding
      ([3H]MK801). In the hippocampal formation and entorhinal cortex nicotine binding
      also declines with age, in common with [125I]alpha-bungarotoxin in the entorhinal
      cortex, but NMDA receptor binding remains unchanged. These reductions in nicotine
      binding with age may predispose the neo- and archicortex to the loss of nAChRs
      observed in age-associated neurodegenerative conditions. By contrast no loss in
      nAChR binding with aging is observed in the thalamus and only after the 70th
      decade in the striatum, although in Alzheimer's disease, Parkinson's disease and
      Lewy body dementia deficits in nAChRs are observed in these areas and may be
      associated with specific disease-related processes.

PMID- 10942043
TI  - The brain alpha7 nicotinic receptor may be an important therapeutic target for
      the treatment of Alzheimer's disease: studies with DMXBA (GTS-21).
AB  - A large decrease in brain nicotinic receptor levels occurs in Alzheimer's
      disease, relative to muscarinic and other receptors. Neurons possessing high
      affinity nicotinic receptors seem particularly vulnerable. The low affinity
      nicotinic receptors which selectively bind alpha-bungarotoxin are not
      significantly affected. The major nicotinic receptor subtype which binds this
      toxin is a homo-oligomer composed of alpha7 subunits. Due to its exceptionally
      high calcium ion selectivity, this particular receptor can be considered as a
      ligand-gated calcium channel. Alpha7 receptors are found in regions of the brain
      which are important for cognition, including cerebral cortex and hippocampus.
      Hippocampal receptors are largely confined to GABAergic interneurons. Alpha7
      receptors seem less likely than alpha4-beta2 receptors to be up-regulated in
      number and down-regulated in function as a result of chronic agonist exposure. A
      family of nicotinic agonists based upon the marine animal toxin anabaseine have
      been synthesized and investigated. One of these compounds, DMXBA [3-(2,4
      dimethoxybenzylidene)-anabaseine; code name GTS-21] has displayed promising
      characteristics during phase I clinical tests. In the rat DMXBA is selectively
      agonistic upon alpha7 nicotinic receptors. In addition it is a moderately potent
      antagonist at alpha4-beta2 receptors. DMXBA enhances a variety of cognitive
      behaviors in mice, monkeys, rats and rabbits. It also displays neuroprotective
      activity upon cultured neuronal cells exposed to beta-amyloid or deprived of NGF.
      The compound is much less toxic than nicotine and does not affect autonomic and
      skeletal muscle systems at doses which enhance cognitive behavior. Phase I
      clinical tests indicate that large doses can be safely administered orally
      without adverse effects. Psychological tests on healthy young male subjects
      indicate a positive effect of DMXBA on some measures of cognition. While DMXBA is
      a much weaker partial agonist on human alpha7 receptors than upon rat alpha7
      receptors, its 4-hydroxy metabolite has been shown to have excellent efficacy on
      both receptors. Thus, some of the physiological and behavioral effects of GTS-21
      may be due to the actions of this primary metabolite.

PMID- 10942044
TI  - Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?
AB  - Nicotine exerts a number of different effects on the nervous system by
      interacting with neuronal nicotinic acetylcholine receptors (nAChRs). These
      effects are mediated by its interaction with different nAChR subtypes, and this
      has led to the finding of subtype specific agonists and antagonists. In the
      search for subtype-selective drugs, we have synthesized some compounds derived
      from 4-oxystilbene, two of which (MG624 and F3) are selective ligands for the
      chick neuronal alphaBgtx receptors containing the alpha7 and/or alpha8 subunits.
      They have an antagonist action on oocyte-expressed chick and rat alpha7 subtypes.
      These compounds are selective toward the alpha7-containing receptors in chick,
      but, in mammals, although they still retain their potency toward alpha7
      containing receptors, they are also active in non-alpha7-containing receptors.

PMID- 10942045
TI  - Tacrine interacts with different sites on nicotinic receptor subtypes in SH-SY5Y
      neuroblastoma and M10 cells.
AB  - The effect of chronic treatment with the cholinesterase inhibitor tacrine on
      nicotinic receptor subtypes was investigated in human SH-SY5Y neuroblastoma cells
      and in a fibroblast cell line (M10 cells) stably transfected with alpha4beta2
      nicotinic receptors. Tacrine significantly increased the number of nicotinic
      receptors in SH-SY5Y cells, in a concentration dependent manner (10(-9) to 10(-4)
      M), when using [3H]epibatidine as labelled ligand. Chronic tacrine treatment of
      M10 cells significantly increased and decreased the number of alpha4beta2
      nicotinic receptors in a concentration dependent manner (10(-9) to 5 x 10(-6) M
      and 2 x 10(-5) to 10(-4) M, respectively). The tacrine induced increase of
      nicotinic receptors in SH-SY5Y cells, was not blocked in the presence of the
      nicotinic antagonists tubocurarine or mecamylamine. A further increase in the
      number of nicotinic receptors was, however, observed in the presence of
      mecamylamine. This study demonstrates that the effect of tacrine on the number of
      nicotinic receptor subtypes is different in human SH-SY5Y neuroblastoma and M10
      cells. The up-regulation of different nicotinic receptor subtypes obtained with
      tacrine might be achieved through interaction via different binding sites on the
      receptor, i.e. the acetylcholine binding site as well as an allosteric site.

PMID- 10942047
TI  - Expression of nicotinic acetylcholine receptors in Alzheimer's disease:
      postmortem investigations and experimental approaches.
AB  - Nicotinic ligand binding studies have shown rather early that the cholinoceptive
      system is affected in Alzheimer's disease (AD). Today, molecular histochemistry
      enables one to study the nicotinic acetylcholine receptor (nAChR) subunit
      expression on the cellular level in human autopsy brains, in animal models and in
      in vitro approaches, thus deciphering the distribution of nAChRs and their role
      as potential therapeutic targets. The studies on the nAChR expression in the
      frontal and temporal cortex of AD patients and age-matched controls could
      demonstrate that both, the numbers of alpha4- and alpha7-immunoreactive neurons
      and the quantitative amount, in particular of the alpha4 protein, were markedly
      decreased in AD. Because the number of the corresponding mRNA expressing neurons
      was unchanged these findings point to a translational/posttranslational rather
      than a transcriptional event as an underlying cause. This assumption is supported
      by direct mutation screening of the CHRNA4 gene which showed no functionally
      important mutations. To get more insight into the underlying mechanisms, two
      model systems organotypic culture and primary hippocampal culture - have been
      established, both allowing to mimic nAChR expression in vitro. In ongoing studies
      the possible impact of beta-amyloid (Abeta) on nAChR expression is tested.
      Preliminary results obtained from primary cultures point to an impaired nAChR
      expression following Abeta exposure.

PMID- 10942046
TI  - Allosterically potentiating ligands of nicotinic receptors as a treatment
      strategy for Alzheimer's disease.
AB  - One of the most prominent cholinergic deficit in Alzheimer's disease (AD) is the
      reduced number of nicotinic acetylcholine receptors (nAChR) in the hippocampus
      and cortex of AD patients, as compared to age-matched controls. This deficit
      results in reduced nicotinic cholinergic excitation which may not only impair
      postsynaptic depolarization but also presynaptic neurotransmitter release and
      Ca2+-dependent intracellular signaling, including transcriptional activity.
      Presently, the most common approach to correct the nicotinic cholinergic deficit
      in AD is the application of cholinesterase inhibitors. Due to the resulting
      increase in synaptic acetylcholine levels, both in concentration and time,
      additional nAChR molecules, e.g. those more distant from the ACh release sites,
      could be activated. As an obvious disadvantage, this approach affects cholinergic
      neurotransmission as a whole, including muscarinic neurotransmission. As a novel
      and alternative approach, a treatment strategy which exclusively targets
      nicotinic receptors is suggested. The strategy is based on a group of modulating
      ligands of nicotinic receptors, named allosterically potentiating ligands (APL),
      which increase the probability of channel opening induced by ACh and nicotinic
      agonists, and in addition decrease receptor desensitization. The action of APL on
      nicotinic receptors is reminiscent of that of benzodiazepines on GABA(A)
      receptors and of that of glycine on the NMDA-subtype of glutamate receptor.
      Representative nicotinic APL are the plant alkaloids physostigmine, galanthamine
      and codeine, and the neurotransmitter serotonin (5HT). The potentiating effect of
      APL on nicotinic neurotransmission has been shown by whole-cell patch-clamp
      studies in natural murine and human neurons, and in murine and human cell lines
      expressing various subtypes of neuronal nAChR.

PMID- 10942048
TI  - The International Network for Cancer Treatment and Research (INCTR).

PMID- 10942049
TI  - African Organisation for Research and Training in Cancer (AORTIC) to be
      reactivated.

PMID- 10942050
TI  - Health spending in UK to rise: how much will there be for cancer?

PMID- 10942051
TI  - Management of relapsed Hodgkin's disease patients with high-dose chemotherapy and
      marrow stem-cell transplantation.

PMID- 10942052
TI  - The contribution of molecular markers to the prediction of response in the
      treatment of breast cancer: a review of the literature on HER-2, p53 and BCL-2.
AB  - BACKGROUND: The selection of therapies for breast cancer is today based on
      prognostic features (chemotherapy, radiotherapy), hormone receptor status
      (hormonal therapy) and HER-2 status (trastuzumab therapy). HER-2, p53 and BCL-2
      are tumour-related proteins that have the potential to further improve
      individualisation of patient management, by predicting response to chemotherapy,
      hormonal therapy and radiotherapy. MATERIALS AND METHODS: This paper reviews the
      rationale for the use of these proteins as predictive factors, as well as the
      published literature addressing the use of each one to predict response to
      hormonal therapy, chemotherapy and radiotherapy. RESULTS: HER-2, p53 and BCL-2
      remain inadequately assessed as predictive factors in breast cancer. HER-2
      evaluation is required for the selection of patients for trastuzumab (Herceptin)
      therapy, as trials of this therapy have been limited to HER-2 overexpressors. HER
      2 overexpression may be predictive of resistance to hormonal therapy.
      Anthracyclines are effective therapy for breast cancer regardless of HER-2
      status, but patients whose tumours overexpress HER-2 appear to receive the
      greatest relative benefit from this therapy. Studies of HER-2 as a predictor of
      response to CMF and to radiotherapy are inconclusive at this time. No data yet
      exist to support the use of p53 or BCL-2 as predictive factors in the therapy of
      breast cancer. CONCLUSIONS: At this point in time, there is inadequate evidence
      to support the use of HER-2, p53 or BCL-2 to guide the selection of hormonal
      therapy, chemotherapy or radiotherapy for breast cancer.

PMID- 10942053
TI  - High-dose BEAM chemotherapy with autologous peripheral blood progenitor-cell
      transplantation for unselected patients with primary refractory or relapsed
      Hodgkin's disease.
AB  - BACKGROUND: The use of autologous peripheral blood progenitor cells (PBPC)
      expedites hematologic recovery and reduces the costs of transplantation in
      comparison with autologous bone marrow; however, its efficacy in patients with
      Hodgkin's disease has been questioned. We evaluated the results of autologous
      PBPC transplantation in a population of unselected and uniformly treated patients
      with primary refractory or relapsed Hodgkin's disease. PATIENTS AND METHODS:
      Forty consecutive adult patients with primary refractory (n = 7) or relapsed (n =
      33) Hodgkin's disease received high-dose BEAM (BCNU, etoposide, ara-C, and
      melphalan) followed by autologous PBPC infusion. Twenty-four patients (60%)
      received high-dose BEAM as outpatients. Consolidative radiation therapy was
      administered to 14 patients (35%). RESULTS: Thirty-seven patients (92%) achieved
      a post transplant complete response. The 3-year progression-free survival (PFS)
      was 69%, and the 3-year overall survival (OS) was 77%, with a median follow-up of
      surviving patients of 28 months. Severe non-hematologic toxicities included
      gastrointestinal side effects (diarrhea 17%, mucositis 25%), and interstitial
      pneumonitis (15%). One patient died of acute transplant-related complications
      (mortality rate 2.5%). Strong predictors of poor PFS were chemoresistant versus
      chemosensitive/untested disease (actuarial PFS 89% versus 22%, P = 0.0000) and
      stage IIB-IV versus I-IIA at relapse/progression (86%, versus 46%, P = 0.005).
      All five patients with elevated lactate dehydrogenase at the time of
      transplantation died of their disease. There was a trend toward worse PFS for
      patients receiving a higher number of CD34+ cells (> or = 11 x 10(6) per kg).
      CONCLUSIONS: High-dose BEAM chemotherapy with autologous PBPC transplantation is
      associated with low mortality and results in satisfactory PFS for patients with
      primary refractory or relapsed Hodgkin's disease. The subset of patients with
      progressive disease at the time of transplantation performs poorly and may
      benefit from alternative strategies.

PMID- 10942055
TI  - Semen analysis and cryoconservation before treatment in Hodgkin's disease.
AB  - BACKGROUND: The prophylaxis of the late effects of chemotherapy and radiotherapy
      has become one of the major concerns in the management of Hodgkin's disease (HD).
      Unlike other complications, male sterility could be managed by prior semen
      preservation (SP). PATIENTS AND METHODS: To evaluate the semen quality of
      patients with HD and the outcome of insemination, we reviewed spermograms of
      patients who underwent SP before any treatment. The following criteria were
      necessary: 1) age > 16 and < 50; 2) HD of any stage; 3) informed about male
      sterility after HD treatment; 4) fully consenting. RESULTS: Such a proposal was
      made to 316 men, and 94 fulfilled the criteria. All patients underwent an initial
      chemotherapy. Mean age of the cohort was 27.5 years (range 16-48 years).
      Pretherapeutic staging of HD revealed 38 stage I (40%), 38 II (38%), 14 III (15%)
      and 4 IV (4%). Semen analysis before cryoconservation showed an overall 53% of
      normal or subnormal cases (50 cases). The analysis of semen quality and
      spermatozoid amount according to various parameters failed to find a correlation
      with stage, B symptoms, age, or biologic data (LDH, WBC, platelets, ESR). The use
      of cryopreserved semen was requested by 13 patients; 88 inseminations were
      performed leading to 9 pregnancies and 2 births. CONCLUSIONS: The low rate of
      success with cryopreserved semen in these cases suggests the need for a more
      careful design of non-toxic chemotherapy regimens in combined modality treatment.

PMID- 10942054
TI  - Multicenter phase II trial of docetaxel and carboplatin in patients with stage
      IIIB and IV non-small-cell lung cancer.
AB  - PURPOSE: To evaluate the safety and efficacy of docetaxel and carboplatin as
      first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: In this multicenter, phase II trial, 33 patients with
      previously untreated stage IIIB (n = 8) or IV (n = 25) NSCLC received intravenous
      infusions of docetaxel 80 mg/m2 followed immediately by carboplatin dosed to AUC
      of 6 mg/ml/min (Calvert's formula) every three weeks. Patients also received
      dexamethasone 8 mg orally twice daily for three days beginning one day before
      each docetaxel treatment. Filgrastim was not allowed during the first cycle and
      was added only if a patient experienced febrile neutropenia or grade 4
      neutropenia lasting > or = 7 days. RESULTS: There were 1 complete and 11 partial
      responses for an objective response rate of 43% (95% CI: 24%-63%) in 28 evaluable
      patients and 36% (95% CI: 20%-55%) in the intent-to-treat population. The median
      duration of response was 5.5 months (range 3.0-12.5 months). The median survival
      was 13.9 months (range 1-35+ months); one-year survival was 52%. The most common
      toxicity was hematologic, which included grade 4 neutropenia (79% of patients and
      7% percent of cycles) and febrile neutropenia (15% of patients); there were no
      episodes of grade 3 or 4 infection. The most common severe nonhematologic
      toxicities were asthenia (24%) and myalgia (12%); there were no grade 3 or 4
      neurologic effects. CONCLUSIONS: The combination of docetaxel and carboplatin has
      an acceptable toxicity profile and is active in the treatment of previously
      untreated patients with advanced NSCLC. This combination is being evaluated in a
      randomized phase III trial involving patients with advanced and metastatic NSCLC.

PMID- 10942056
TI  - Incidence and risk factors of central nervous system relapse in histologically
      aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal
      central nervous system prophylaxis: a GELA study on 974 patients. Groupe d'Etudes
      des Lymphomes de l'Adulte.
AB  - BACKGROUND: Incidence of central nervous system (CNS) recurrence in patients with
      aggressive non-Hodgkin's lymphoma who did not receive meningeal prophylaxis is
      about 5%. Controversy remains regarding risk factors associated with such an
      event preventing a rational approach of prophylactic strategies. PATIENTS AND
      METHODS: We analyzed a cohort of 974 patients with aggressive lymphoma in
      complete remission (CR). All the patients received a CNS prophylaxis consisting
      of intrathecal injections and intravenous high-dose methotrexate. The risk
      repartition on the basis of the international prognostic index (IPI) of these 974
      CR-patients was low (L): 41%, low-intermediate (LI): 27%, high-intermediate (HI):
      19%, high (H): 13%. RESULTS: The incidence of isolated CNS relapse was 1.6%. In a
      first multivariate logistic regression analysis an increased LDH (P = 0.05, RR =
      5) and the presence of more than one extranodal site (P = 0.05, RR = 3) were
      identified as independent risk factors for isolated CNS relapse. Another
      multivariate analysis incorporating IPI as a unique parameter showed that only
      IPI remained significantly associated with a higher risk of CNS relapse (L-LI:
      0.6% vs. HI H: 4.1%, P = 0.002; RR = 7). CONCLUSION: Prophylaxis notably reduces
      the risk of CNS recurrence in the higher risk patients. By contrast, we propose
      the deletion of prophylactic intrathecal injections in the lower risk patients.

PMID- 10942057
TI  - A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL.
AB  - BACKGROUND: Standard therapy for lymphoma consists of a cyclophosphamide (C),
      doxorubicin, vincristine (V), and prednisone (P) (CHOP) combination regimen.
      Liposomal daunorubicin (DaunoXome) is an alternative to doxorubicin for patients
      with lymphoma because of its more favorable safety profile and potentially more
      selective uptake in lymphoma. The objectives of this study were to determine the
      maximum tolerated dose (MTD) of liposomal daunorubucin with CVP (COP-X) and the
      tolerability of the regimen in patients with indolent lymphoma. PATIENTS AND
      METHODS: Patients with low-grade and intermediate-grade lymphoma having adequate
      cardiac, hepatic, and renal function were enrolled. Patients received C 750
      mg/m2, V 1.4 mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50-100 mg/m2 i.v.
      on day 1 and P 100 mg p.o. on days 1-5. MTD was the liposomal daunorubicin dose
      associated with 20% dose-limiting toxicity (ANC < 500/mm3 for > 5 days or febrile
      neutropenia). RESULTS: Twenty patients, median age 59 years, were treated. The
      liposomal daunorubicin MTD combined with CVP was 70-80 mg/m2, depending on
      patient population. No significant non-hematologic toxicity occurred. Response
      rate was 44% (2 complete and 5 partial responses). CONCLUSIONS: A liposomal
      daunorubicin dose of 80 mg/m2 in the COP-X regimen was well tolerated with little
      nonhematologic toxicity.

PMID- 10942058
TI  - Caelyx in malignant mesothelioma: a phase II EORTC study.
AB  - BACKGROUND: The use of doxorubicin has shown some activity in malignant
      mesothelioma but prolonged administration is hampered by cardiotoxicity. Caelyx,
      a new liposomal and pegylated form of doxorubicin has shown a better
      pharmacokinetic and toxic profile then doxorubicin. In a phase II study, the
      efficacy and toxicity of Caelyx was tested in previously untreated patients with
      malignant pleural mesothelioma. PATIENTS AND METHODS: Thirty-three patients who
      had measurable or evaluable histologically confirmed malignant pleural
      mesothelioma were included in the study. Caelyx (45 mg/m2) was given i.v. on
      outpatient base every four weeks for nine cycles or till progression or
      unacceptable toxicity occurred. RESULTS: Of the 33 patients, 32 were evaluable
      for toxicity and 31 for response. Two patients had a partial response (6%, 95%
      confidence interval: 0.2%-20.2%). The median survival was 13 months. Forty
      percent of the patients received >6 cycles. Toxicity was mild with palmar plantar
      erythrodysesthesia being most pronounced (62% grade 1-2, 6% grade 3) and of
      limited duration. Ten percent of patients had grade 3 anemia and 3% grade 3
      thrombocytopenia. Two patients (6%) had grade 3 or 4 cardiac toxicity, which was
      not drug related. CONCLUSION: At the prescribed dose, single agent Caelyx is well
      tolerated but its activity in chemotherapy-naive mesothelioma patients does not
      warrant further investigation as a single agent.

PMID- 10942059
TI  - Sentinel node biopsy as a practical alternative to axillary lymph node dissection
      in breast cancer patients: an approach to its validity.
AB  - BACKGROUND: Sentinel node biopsy (SNB) has been proposed as an alternative to
      axillary lymph-node dissection (ALND) in breast cancer. Before implementing SNB
      in our practice, we wished to test its validity by comparing it to the standard
      ALND, both in our hands and with other reported series. PATIENTS AND METHODS: One
      hundred thirty-two patients were included prospectively. SNB and immediate ALND
      were performed. For SNB, a technetium-colloid was used to produce preoperative
      lymphoscintigraphy and intraoperative gamma-probe search for the SN. Serial
      sectioning and immunostains were used on the SN. A comprehensive review of the
      literature was done in order to run a meta-analysis of diagnostic tests using a
      summary receiver operating characteristic curve (SROC) to calculate the pooled
      parameters of sensitivity and associated 95% confidence interval (95% CI),
      including our own data. RESULTS: Our technical success rate was 96%. Local
      sensitivity was 96%, with a 95% CI from 85%-99%. Seven patients were upstaged by
      the SNB. A literature search identified 18 studies published from 1996-1999.
      Estimates of sensitivity ranged from 83%-100%. The pooled data meta-analysis gave
      a global sensitivity of 91%, with a 95% CI from 89%-93%. The area under the
      global SROC curve was 0.9967. CONCLUSIONS: The minimally invasive SNB was shown
      to be a practical alternative to ALND. We propose to use local as well as global
      sensitivity and associated 95% CI to test the validity of SNB in the clinical
      setting. Due to limitations of ALND as the golden standard, SNB can in fact be
      considered a more accurate method for nodal staging.

PMID- 10942060
TI  - The interferon-alpha regulation of interferon regulatory factor 1 (IRF-1) and IRF
      2 has therapeutic implications in carcinoid tumors.
AB  - BACKGROUND: Interferon regulatory factor 1 (IRF-1) has been demonstrated to
      possess antiproliferative and tumor suppressor functions, on the contrary. IRF-2
      has been suggested to induce oncogenetic effect in some cell lines, but not
      evaluated in tumor patients. PATIENTS AND METHODS: In 35 carcinoid tumor
      patients, expressions of IRF-1 and IRF-2 were investigated by
      immunohistochemistry and their values were analyzed with clinical treatment
      response. In carcinoid tumor cell line, Bonl, effects of IFN-alpha on the
      expression of both IRF-1 and IRF-2 mRNAs and proteins were determined by Northern
      blot, RNase protection assays and Western blot analysis. RESULTS: IFN-alpha up
      regulated the expression of IRF-1 and IRF-2 both in vivo and in vitro. In
      carcinoid tumors, IFN-alpha treatment led to a significant increase in the
      expression of IRF-1 (P < 0.001) and IRF-2 (P < 0.001). Moreover, the IRFs
      induction was correlated with the clinical response of IFN-alpha treatment,
      although their baseline values were not predictive. In addition, expressions of
      IRF-1 and IRF-2 were significantly correlated with the p68 kinase expression (P =
      0.032 and P = 0.0176, respectively) and the expression of IRF-1 protein was
      positively correlated with that of IRF-2 (r = 0.671, P = 0.0001) tested in the
      same specimens. CONCLUSIONS: IRF-1 as well as IRF-2 have therapeutic implications
      in carcinoid tumors during treatment with interferon-alpha and IRFs induction
      might be used as indicators of response to treatment with interferon-alpha.

PMID- 10942061
TI  - Patterns of relapse and subsequent management following high-dose chemotherapy
      with autologous haematopoietic support in relapsed or refractory Hodgkin's
      lymphoma: a two centre study.
AB  - BACKGROUND: High-dose chemotherapy has an established role in recurrent or
      refractory Hodgkin's lymphoma (HL) although a significant proportion of patients
      subsequently relapse. This manuscript describes the clinical characteristics of
      such patients and documents their further management at two major UK cancer
      centres. PATIENTS AND METHODS: Between 1987 and 1996 one hundred patients with
      recurrent or refractory HL received high-dose chemotherapy (HDCT) with autologous
      haematopoietic rescue. All had recurred within 12 months of initial therapy or
      had two or more recurrences. RESULTS: With a median follow-up of 2 years, 56
      patients are currently progression-free. There were six treatment-related deaths.
      One patient died of pneumonia in remission. Thirty-seven patients have relapsed,
      intrapulmonary disease being seen for the first time in 53% and recurrence at
      previous sites of disease in 81%. Following recurrence, therapy was determined by
      circumstances: either one agent at a time was used (single sequential approach)
      or multiagent chemotherapy was chosen. There was a survival advantage for those
      who achieved a symptomatic response (13 vs. 4 months median, P = 0.0001). A trend
      towards longer survival was seen for those whose disease recurred beyond six
      months following high-dose chemotherapy and in those who received combination
      chemotherapy. CONCLUSIONS: These results confirm that HDCT with autologous
      haematopoietic support is inadequate for about half the patients who receive it
      for high-risk HL. Relapse in the site of prior disease is the most likely pattern
      with intrapulmonary disease for the first time occurring frequently. It is
      possible to administer further chemotherapy after failure of HDCT, and both
      objective as well as subjective benefit can be achieved. A few patients appear to
      get long-term benefit from further treatment.

PMID- 10942062
TI  - A phase I-II study of concomitant chemoradiotherapy with paclitaxel (one-hour
      infusion), 5-fluorouracil and hydroxyurea with granulocyte colony stimulating
      factor support for patients with poor prognosis head and neck cancer.
AB  - BACKGROUND: Concomitant chemoradiotherapy is an effective treatment modality for
      advanced head and neck cancer, but improved regimens are needed. We sought to
      define the toxicities, recommended phase II dose, and outcome of a combination
      chemotherapy regimen with concomitant hyperfractionated radiotherapy in patients
      with poor prognosis cancers of the head and neck, including those having received
      prior curative intent radiotherapy. PATIENTS AND METHODS: From 1995 until 1997,
      54 patients were treated, 25 of whom had received a prior full course of
      radiotherapy to the head and neck. Patients were treated with 5-fluorouracil (5
      FU) 600 mg/m2/day continuous infusion x 5 days (days 1-5), hydroxyurea, 500 mg
      p.o. bid x 11 doses (days 1-6) and paclitaxel (60-150 mg/m2) by one-hour infusion
      on day 2 using a dose escalation strategy. Radiotherapy was given concomitantly
      on days 2-6, 150 cGy bid. Each of 4-5 cycles was delivered every other week.
      RESULTS: The MTD of paclitaxel was 100 mg/m2. The regimen was feasible;
      radiotherapy was delivered at a median of 7300 cGy and 83% of patients received >
      or = 80% planned dose intensity. Hematological toxicity, with granulocyte colony
      stimulating factor, was very mild. Dose limiting toxicities were mucositis and
      dermatitis. Despite poor prognosis, two-year survival was 45%. CONCLUSIONS: The
      recommended phase II dose of this regimen is 5-FU 600 mg/m2/day x 120 hours (days
      1-5), hydroxyurea 500 mg p.o. b.i.d. x 11 doses (days 1-6), paclitaxel 100 mg/m2
      over one hour on day 2, and radiotherapy 150 cGy b.i.d. days 2-6. Concomitant
      chemotherapy and re-irradiation was feasible on this protocol and resulted in
      long-term survival in patients without other curative intent options.

PMID- 10942063
TI  - Weekly administration of bendamustine: a phase I study in patients with advanced
      progressive solid tumours.
AB  - BACKGROUND: The cytotoxic agent bendamustine combines a purine-like benzimidazol
      and alkylating nitrogen mustard group. The clinically tolerated dose for single
      bolus bendamustine is 215 mg/m2, for fractionated therapy on four consecutive
      days 85 mg/m2. The maximum tolerated dose of a day 1 and 8 (q4w) 30 min infusion
      schedule was recently found to be 160 mg/m2, mouth dryness and fatigue were dose
      limiting. Our current phase I trial was designed to define the recommended dose
      of a new weekly short infusion schedule. PATIENTS AND METHODS: Patients with
      refractory malignant tumours qualified for the trial after written informed
      consent was obtained. Bendamustine was given as a 30-min i.v. infusion weekly for
      up to eight consecutive weeks. RESULTS: Twelve patients (8 male, 4 female, median
      age 57.5 years, range 42-64) were enrolled in this trial. At the starting dose of
      80 mg/m2, two patients had dose-limiting toxicity (fatigue grade 3, mouth dryness
      grade 3, fever grade 4 Common Toxicity Criteria). No dose-limiting events were
      observed in six patients treated at 60 mg/m2. An intermediate dose level of 70
      mg/m2 was studied in three younger, less heavily pretreated patients, was well
      tolerated and not associated with dose-limiting events. Haematological toxicity
      was mild except for grade 3-4 lymphocytopenia, occurring in 11 of 12 patients.
      Bendamustine was found to induce long-lasting panlymphocytopenia with predominant
      B-cell cytotoxicity. CONCLUSIONS: The maximum tolerated dose of weekly
      bendamustine given as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigue
      and fever are dose-limiting. The recommended dose for phase II trials is 60
      mg/m2.

PMID- 10942064
TI  - Phase I open study of the effects of ascending doses of the cytotoxic
      immunoconjugate CMB-401 (hCTMO1-calicheamicin) in patients with epithelial
      ovarian cancer.
AB  - PURPOSE: We have performed a phase I study of the cytotoxic immunoconjugate CMB
      401 in women with epithelial ovarian cancer (EOC). CMB-401 is a directed
      chemotherapy that comprises a genetically engineered human antibody against
      polymorphic epithelial mucin, to which is attached covalently two to three
      molecules, on average, of the cytotoxic antibiotic calicheamicin. The primary
      objectives of this two-centre study were to identify end-organ toxicities and to
      establish the maximum tolerated dose (MTD). PATIENTS AND METHODS: Thirty-four
      patients aged 37-75 years with progressive EOC not amenable to platinum/standard
      therapy, and with satisfactory WHO performance status (0-2) were recruited.
      Patients had received a mean of 3.2 previous chemotherapeutic regimens with a
      median interval since last chemotherapy of 182 days (range 34-1217). Patients
      received up to four cycles of a dual infusion of 35 mg/m2 hCTMO1 'predose'
      followed by doses of CMB-401 which were increased for each cohort--a regimen
      which minimises drug uptake in normal tissues whilst enhancing delivery to the
      ovarian tumour. CMB-401 dosing commenced at 2 mg/m2 and progressed via seven
      cohorts to 16 mg/m2. RESULTS: CMB-401 was generally well tolerated. However,
      transient fever and emesis occurred, necessitating routine prophylaxis, and
      increasingly significant malaise was reported as the dose increased. WHO grade 3
      4 toxicities, irrespective of causality, included: anaemia 21%, granulocytopenia
      9%, thrombocytopenia 9%, liver transaminases 3%, sepsis 3%, haemorrhage 6%,
      nausea/vomiting 76%; pulmonary 6%, and conscious state/somnolence 6%. The MTD was
      reached at 16 mg/m2. During the study four patients had a greater than 50%
      reduction in CA125, and three patients had radiological evidence of reduction in
      tumour bulk. CONCLUSIONS: CMB-401 appears to have an acceptable toxicity profile
      with demonstrable activity against EOC.

PMID- 10942065
TI  - Acute deterioration of Charcot-Marie-Tooth disease IA (CMT IA) following 2 mg of
      vincristine chemotherapy.
AB  - BACKGROUND: Severe up to life-threatening neuropathy has been observed in
      patients with hereditary neuropathies receiving vincristine. CASE REPORT: A 52
      year-old female painter suffering from high-grade non-Hodgkin's lymphoma (stage
      IVB) was treated with a total of 4 mg of vincristine during two courses of CHOP
      chemotherapy (cyclophosphamide, vincristine, adriamycin, prednisone). At onset of
      treatment no neurological problems were reported. There was good lymphoma
      response to chemotherapy. At the same time, however, the patient gradually
      developed dysphagia, dysarthria, muscular weakness of both lower and upper
      extremities, areflexia, paraesthesia of the fingertips and bilateral sensory
      impairment of feet and lower legs. These symptoms continually worsened over a
      period of seven weeks until she was unable to walk or to perform her work.
      Electrophysiological studies showed peripheral axonal and demyelinative
      sensorimotor neuropathy in correlation to histological findings. Molecular
      analysis revealed 17p11.2 duplication typical for Charcot-Marie-Tooth disease IA.
      While continuing chemotherapy without the use of vincristine the patient's
      neurologic symptoms slowly recovered within six months. CONCLUSION: Prior to
      administration of vincristine family and patient history as well as physical
      examination should be performed carefully to look for underlying hereditary
      neuropathy. For those patients with a clinical history or symptoms suggestive for
      CMT nerve conduction velocity studies and on an individual base even molecular
      genetic analysis are necessary to prevent serious neurologic complications.
      worsened significantly resulting in dependency on a wheelchair and inability to
      perform her work as a painter. Finally she consulted a neurologist and was
      admitted to hospital for further diagnostic studies and continuation of treatment
      for her lymphoma in March 1998 with a provisional diagnosis of severe vincristine
      induced neuropathy. Medical history at time of admission included
      hyperthyroidism, that was currently treated with propylthiouracil, a MALT
      lymphoma 1983, that was treated surgically only, and a meningoencephalitis in
      1968. No further medication was taken. In addition she had a history of Lyme
      disease since 1993 with positive IgM-titer until December 1997, when antibiotic
      therapy with doxycycline and ceftriaxone was administered successfully. Family
      history obtained on admission revealed that her mother had non-specific
      neuropathic symptoms as well as a poorly defined foot deformities of the mother's
      father. The patient's brother does not show any neurologic impairment and is in
      good physical health.

PMID- 10942066
TI  - Metastatic extragonadal seminoma associated with cardiac transplantation.
AB  - A 37-year-old man who had successfully undergone cardiac transplantation for
      dilated cardiomyopathy presented with a history of severe pain over his left
      shoulder, rib cage and thoracic spine. Clinical examination revealed the presence
      of bony tenderness over these sites, but there was no other clinical evidence of
      malignancy. Further investigations suggested the presence of multiple bony
      metastases. Bone biopsy revealed extensive bone marrow infiltration by large
      undifferentiated cells showing pronounced cytoplasmic vacuolation with a striking
      granulomatous reaction. Immunocytochemistry revealed these anaplastic cells to be
      cytokeratin and placenta-like alkaline phosphatase positive but S100, CD30 and
      lymphoid marker negative. Analyses by in situ hybridisation of these cells
      revealed no evidence of Epstein-Barr virus infection. Overall the pathology
      suggested a diagnosis of metastatic seminoma. Confirmation of this diagnosis was
      obtained by the analysis of serum human chorionic gonadotrophin which was
      elevated at 90 IU/l. In the absence of testicular or retroperitoneal disease, it
      is very likely that this unusual case of metastatic seminoma was related to the
      patient's immunosuppressive therapy, which at diagnosis included cyclosporin and
      prednisolone. The patient was successfully treated with cisplatin based
      chemotherapy and decreased immunosuppression and remains in complete remission
      one year after completion of chemotherapy. Seminoma is an uncommon complication
      of prolonged immunosuppression with very few cases being described in the
      literature post-organ transplantation. This case shows that the clinical
      presentation of this treatable tumour in this patient population can be unusual
      and difficult to diagnose.

PMID- 10942067
TI  - Malignant peritoneal mesothelioma treated by continuous hyperthermic peritoneal
      perfusion chemotherapy.
AB  - Malignant mesothelioma of the peritoneum is a rare tumour for which the
      therapeutic approach has not yet been standardized. The efficacy of the current
      regimes is limited. Effective locoregional therapy is crucial, since this tumour
      is most often confined to the peritoneal cavity at the time of the initial
      diagnosis and remains there for much of its clinical course. If and when
      haematogenous metastases occur, they rarely contribute to the death of the
      patient, which is often caused by the overgrowth of the primary tumour and its
      local complications. A case of diffuse malignant peritoneal mesothelioma treated
      by cytoreductive surgery and continuous hyperthermic peritoneal perfusion with
      cisplatin is reported. The patient received systemic combination chemotherapy
      postoperatively. She is in good condition and free of disease 28 months after her
      treatment. Continuous hyperthermic peritoneal perfusion chemotherapy has recently
      been used in patients with secondary peritoneal carcinomatosis from digestive and
      gynecological malignancies with promising results. It is also possible that the
      same treatment alone or in combination with systemic chemotherapy may be
      effective in the treatment of primary peritoneal malignancies, as in the case of
      diffuse peritoneal mesothelioma.

PMID- 10942069
TI  - Serum endostatin levels in patients with hepatocellular carcinoma.

PMID- 10942068
TI  - Salvage treatment of advanced non-small-cell lung cancer previously treated with
      docetaxel-based front-line chemotherapy with irinotecan (CPT-11) in combination
      with cisplatin.
AB  - BACKGROUND: A phase II study was conducted in order to determine the toxicity and
      efficacy of the combination of CPT-11 and cisplatin, as salvage treatment in
      patients with advanced non-small-cell lung cancer (NSCLC), progressing after a
      docetaxel-based front-line regimen. PATIENTS AND METHODS: Thirty-one patients
      (median age 61 years) with NSCLC, were enrolled. Twenty-six (84%) patients were
      male, twenty-five (81%) had disease stage IV, and twenty-eight (90%) had a
      performance status (WHO) 0-1. CPT-11 was administered as a 60-minute i.v.
      infusion at the dose of 100 mg/m2 on day 1 and 110 mg/m2 on day 8; cisplatin was
      administered at the dose of 80 mg/m2 on day 8, after CPT-11 administration.
      Treatment was repeated every three weeks. RESULTS: A total of 110 chemotherapy
      cycles were administered. In an intention-to-treat analysis 7 patients (23%; 95%)
      Introduction confidence interval (95% CI): 8%-37%) achieved a partial response, 6
      (19%) had stable disease, and 18 (58%) progressive disease. Three of responders
      had failed a previous docetaxel-carboplatin combination. The median duration of
      response was 3 months, the median TTP 8 months and the median survival for the
      entire group 8 months. Grade 3-4 neutropenia was observed in 16 (52%) patients
      and in two cases this was febrile. Grade 3 and 4 thrombocytopenia occurred in two
      (7%) patients, respectively. Grade 3 and 4 diarrhea was seen in 10 (33%)
      patients, grade 2-3 neurotoxicity in 2 (6%), and fatigue grade 2-3 in 12 (39%).
      Other toxicities were mild. CONCLUSIONS: The combination of CPT-11 and cisplatin
      has manageable toxicity and interesting activity as salvage treatment of patients
      with advanced NSCLC, previously treated with a docetaxel-based front-line
      regimen.

PMID- 10942070
TI  - Phase II trial of low-dose cyclophosphamide, leucovorin, high-dose 5-fluorouracil
      24-hour continuous infusion and tamoxifen in advanced biliary tract cancer.

PMID- 10942071
TI  - Mast cells in UV-B-induced immunosuppression.
AB  - Degranulating dermal mast cells in UV-B-irradiated skin have been implicated for
      many years in the mechanisms of irradiation erythema. There is now considerable
      evidence that dermal mast cells are important to the processes by which both UV-B
      radiation and cis-urocanic acid (cis-UCA) suppress immune responses to
      sensitizing antigens applied to non-irradiated/non-cis-UCA-exposed sites. Mast
      cell-depleted mice are resistant to the immunosuppressive effects of UV-B
      radiation and cis-UCA for 'systemic' immunomodulation. However, these mice gain
      responsiveness if the dorsal skin is reconstituted six weeks prior to irradiation
      or cis-UCA administration at that site with cultured bone-marrow-derived mast
      cells from +/+ mice. The molecular triggers for initiating mast-cell
      degranulation are being actively sought. Evidence suggests that histamine, and
      not tumour necrosis factor alpha, is the major mast-cell product that signals
      altered immune responses to sensitizing antigens applied to non-irradiated, non
      cis-UCA-exposed sites. Histamine may have multiple roles, but experiments with
      indomethacin administered to mice have shown that one process involves induction
      of prostanoid production.

PMID- 10942072
TI  - Photobehaviour of Hydra (Cnidaria, Hydrozoa) and correlated mechanisms: a case of
      extraocular photosensitivity.
AB  - The morpho-functional organization correlated to photosensitivity in Cnidaria is
      that of ocelli and extraocular photoreception. Several examples of the second
      type of organization are reported. The photosensitivity of the cnidarian Hydra is
      of the extraocular (neural or dermal) type. The effects of photic stimulation
      (applied according to various experimental protocols: steady condition; step
      stimulus; single, twin, or repetitive pulses; different polarities and
      chromaticities of steady, step and pulse stimulation and different phases of
      pulse application) on the modulation of various bioelectric events linked to the
      periodic behaviour of the animal are reviewed. The mechanisms correlated with the
      photobehaviour of Hydra, as well as the problems still open on the molecular
      mechanisms of phototransduction, are discussed.

PMID- 10942073
TI  - The fluorescent oxidation products of dihydroxyphenylalanine and its esters.
AB  - Dihydroxyphenylalanine (DOPA), its methyl ester (DOPAM) and the N-acetylated
      derivative of the ester (DOPAMNA) are found to undergo rapid oxidation in air
      saturated alkaline solution. Some of the products of oxidation exhibit
      fluorescent emission in the 300-500 nm spectral range and their excitation
      emission spectra have been determined in acidic and alkaline aqueous solutions.
      The spectral distributions and positions of the maxima depend on the pH of the
      solution. Excitation-emission maxima associated with the protonated phenolic form
      of the compounds occur at shorter wavelengths than those of the conjugate base.
      At some pH values the phenolic forms of these molecules are excited and undergo
      rapid deprotonation in the excited state; as a consequence, emission is observed
      from the phenolate anion. The fluorescence excitation-emission spectrum of an
      authentic sample of 3,4-dihydroxycinnamic (caffeic) acid has also been determined
      and features of the fluorescence spectra of the principal oxidation products are
      consistent with the presence of 3,4-hydroxycinnamoyl compounds in solutions of
      oxidized DOPAM and DOPAMNA.

PMID- 10942074
TI  - UV-B-induced generation of free radicals in blood platelets.
AB  - UV-B irradiation of blood-platelet concentrates is used in transfusion practice
      to prevent the development of post-transfusion alloimmunization and inactivate
      viruses and bacteria in the concentrates. UV-B radiation may affect the blood
      platelet metabolism and function; therefore we have investigated the effect of UV
      B irradiation on free radical production in blood platelets. Our results show
      that exposure of pig blood platelets to UV-B radiation (0.36 and 1.08 J/cm2)
      induces the generation of free radicals measured by the chemiluminescence method
      (respectively 28 and 148.6% above the control). The superoxide radical level
      after UV-B irradiation measured by the cytochrome c reduction method shows only a
      slight increase (p > 0.05). Free radical generation induced by UV-B radiation is
      dependent partly on blood-platelet activation and enzymatic pathways, since we
      have shown that wortmannin, an inhibitor of phosphatidylinositide 3-kinase,
      reduces the level of radicals formed in blood platelets after UV-B irradiation.
      This indicates that free radicals generated in blood platelets after stimulation
      by UV-B radiation are involved in platelet activation and metabolism of platelet
      polyphosphoinositides.

PMID- 10942075
TI  - Antioxidant adaptive response of human mononuclear cells to UV-B: effect of
      lipoic acid.
AB  - Supplementation of human mononuclear cells with 3 and 6 mM of lipoic acid
      produces an inhibition of the antioxidant adaptive response triggered by
      treatment with UV-B light (0.30 W/m2 for 15 min). Supplementation with 1.5 mM of
      lipoic acid gives no conclusive results. The adaptive response is characterized
      by an increase in the activities of superoxide dismutase, catalase, glutathione
      peroxidase and DT-diaphorase. Catalase (5.5 +/- 0.6 pmol/mg prot) increases its
      activity by up to 22 +/- 3 pmol/mg prot, after irradiation with UV-B.
      Supplementation with 3 and 6 mM of lipoic acid completely inhibits the adaptive
      response. The activities of the membrane-bound mitochondrial enzymes succinate
      dehydrogenase and cytochrome oxidase do not increase after UV-B exposure.
      Moreover, their activities are found to decrease and the addition of lipoic acid
      does not prevent this effect. The inhibition of the antioxidant response by
      lipoic acid in human cells appears as indirect evidence of the existence of
      oxidative stress in the development of this response. As lipoic acid behaves as
      an effective antioxidant, it seems that its action decreases the intracellular
      oxidative signals necessary to develop the adaptive response in human mononuclear
      cells.

PMID- 10942076
TI  - Contribution of phosphoinositide-dependent signalling to photomotility of
      Blepharisma ciliate.
AB  - The effect of experimental procedures designed to modify an intracellular
      phosphoinositide signalling pathway, which may be instrumental in the photophobic
      response of the protozoan ciliate Blepharisma japonicum, has been investigated.
      To assess this issue, the latency time of the photophobic response and the cell
      photoresponsiveness have been assayed employing newly developed computerized
      videorecording and standard macro-photographic methods. Cell incubation with
      neomycin, heparin and Li+, drugs known to greatly impede phosphoinositide
      turnover, causes evident dose-dependent changes in cell photomotile behaviour.
      The strongest effect on photoresponses is exerted by neomycin, a potent inhibitor
      of polyphosphoinositide hydrolysis. The presence of micromolar concentrations of
      neomycin in the cell medium causes both prolongation of response latency and
      decrease of cell photoresponsiveness. Neomycin at higher concentrations (> 10
      microM) abolishes the cell response to light at the highest applied intensity. A
      slightly lower inhibition of cell responsiveness to light stimulation and
      prolongation of response latency are observed in cells incubated in the presence
      of heparin, an inositol trisphosphate receptor antagonist. Lithium ions, widely
      known to deplete the intracellular phosphoinositide pathway intermediate,
      inositol trisphosphate, added to the cell medium at millimolar level, also cause
      a slowly developing inhibitory effect on cell photoresponses. Mastoparan, a
      specific G-protein activator, efficiently mimics the effect of light stimulation.
      In dark-adapted ciliates, it elicits ciliary reversal with the response latency
      typical for ciliary reversal during the photophobic response. Sustained treatment
      of Blepharisma cells with mastoparan also suppresses the photoresponsiveness, as
      in the case of cell adaptation to light during prolonged illumination. The
      mastoparan-induced responses can be eliminated by pretreatment of the cells with
      neomycin. Moreover, using antibodies raised against bovine transducin, a cross
      reacting protein with an apparent molecular mass of about 55 kDa in the
      Blepharisma cortex fraction is detected on immunoblots. The obtained results
      indirectly suggest that the changes in internal inositol trisphosphate level,
      possibly elicited by G-protein-coupled phospholipase C, might play a role in the
      photophobic response of Blepharisma. However, further experiments are necessary
      to clarify the possible coupling between the G-protein and the putative
      phospholipase C.

PMID- 10942078
TI  - Preparation protocols for high-activity photosystem II membrane particles of
      green algae and higher plants, pH dependence of oxygen evolution and comparison
      of the S2-state multiline signal by X-band EPR spectroscopy.
AB  - Photosystem II (PS II) membrane particles are particularly well suited for
      various types of spectroscopic investigations on the PS II manganese complex.
      Here we present: (1) a preparation protocol for PS II membrane particles of
      higher plants, which yields exceptionally high oxygen-evolution activity due to
      the use of glycinebetaine as a PS II-stabilizing agent; (2) preparation protocols
      for highly active PS II membrane particles for the green algae Scenedesmus
      obliquus and Chlamydomonas reinhardtii; (3) a determination of pH dependence of
      oxygen evolution for spinach and Scenedesmus; (4) a comparison of the EPR
      multiline signal observed in the S2-state of green algae and higher plants of PS
      II membrane particles. A clearly broader type of multiline EPR signal is observed
      in green algae.

PMID- 10942077
TI  - Skin-photosensitizing properties of Zn(II)-2(3), 9(10), 16(17), 23(24)-tetrakis
      (4-oxy-N-methylpiperidinyl) phthalocyanine topically administered to mice.
AB  - A Zn-phthalocyanine derivative bearing four 4-oxy-N-methyl-piperidinyl peripheral
      substituents has been formulated in an azone-containing gel for topical
      administration and its potential as a photodynamic therapy agent has been
      investigated. The phthalocyanine displays an intense absorbance in the 680 nm
      range and shows a high photosensitizing activity toward a model biological
      substrate (N-acetyl-L-tryptophanamide). Upon administration of 20 microg cm(-2)
      onto the dorsal skin of Balb/c mice, maximal phthalocyanine concentrations (ca.
      64.2 ng mg(-1) of skin) are reached at 1 h after the deposition. The
      photosensitizer appears to be localized in the epidermal layers, since (a) no
      detectable amounts of phthalocyanine are recovered from the mouse blood and
      liver; and (b) upon photoactivation with a diode laser at 675 nm, only the
      epidermis is heavily damaged, as shown by histological and ultrastructural
      analysis. The photodamage is largely of inflammatory nature and an essentially
      complete healing of the damaged skin is observed at 72 h after the end of the
      phototreatment. The minimal phototoxic dose for 20 microg cm(-2) photosensitizer
      and 675 nm irradiation is found to be (150 mW cm(-2)-120 J cm(-2)) or (180 mW cm(
      2)-100 J cm(-2)).

PMID- 10942079
TI  - Spectroscopic detection of photoproducts in lecithin model system after 8
      methoxypsoralen plus UV-A treatment.
AB  - Photoreactions of 8-methoxypsoralen (8-MOP) in the presence of synthetic
      lecithins esterified at the beta-position with linoleic/oleic and gamma-palmitic
      acid (PCd2/d1pal) have been studied. Following UV-A (320-400 nm) irradiation, the
      photoproducts separated by thin-layer chromatography are analysed by UV
      absorption spectroscopy, nuclear magnetic resonance and mass spectroscopy. The
      new isolated products are lecithin double cyclobutane adducts, PC-(8-MOP)2, fatty
      acid-8-MOP split adducts from phosphatidylcholine and lecithin adducts with photo
      oxidized 8-MOP. The photolysis performed in the presence of 8-MOP is related to
      the previously reported lecithin cyclobutane adducts with psoralen. A
      hypothetical scheme of lecithin photolysis under PUVA (psoralen + UV-A) treatment
      is proposed. We suggest that photolysis of lecithin may have a significant role
      in the chain of reactions triggered in cell membrane submitted to PUVA treatment.

PMID- 10942080
TI  - Light-stress-induced pigment changes and evidence for anthocyanin photoprotection
      in apples.
AB  - Fruit of two apple (Malus domestica Borkh.) cultivars, differing in their ability
      to produce anthocyanin pigments when exposed to sunlight, have been studied using
      reflectance spectroscopy. Comparison of the spectra shows that apple anthocyanins
      in vivo possess a symmetric absorption band at 500-600 nm with a maximum near 550
      nm. Anthocyanins considerably increase light absorption by apples. In on-tree
      ripening Zhigulevskoe apples, accumulating high amounts of anthocyanin pigments,
      chlorophyll contents in sunlit and shaded sides of the fruits are found to be
      similar. In contrast, frequently considerably lower chlorophyll content is
      estimated in sunlit compared with shaded sides of Antonovka apples exhibiting low
      potential for anthocyanin formation. Sunlight also brings about an increase of
      carotenoid content over that of chlorophylls and accumulation of substances
      responsible for light absorption in the range 350-400 nm. The rates of high-light
      induced chlorophyll bleaching in red zones of fruit containing anthocyanins are
      considerably lower than those in green zones and decrease with an increase in the
      pigment content. Anthocyanins show more stability to irradiation than
      chlorophylls. A protective function of anthocyanins against both light-induced
      stress in, and damage to, apples is suggested. It is proposed that anthocyanins
      function as an effective internal light trap filling the chlorophyll absorption
      gap in the green-orange part of the visible spectrum.

PMID- 10942081
TI  - A comparative study of the cellular uptake, localization and phototoxicity of
      meta-tetra(hydroxyphenyl) chlorin encapsulated in surface-modified submicronic
      oil/water carriers in HT29 tumor cells.
AB  - The poor selectivity of photosensitizers for tumor tissue remains a drawback in
      photodynamic therapy (PDT) and could be improved by adapted formulations. The
      cellular uptake, localization and phototoxicity of meta
      tetra(hydroxyphenyl)chlorin (mTHPC) encapsulated in submicronic colloidal
      carriers have been studied in macrophage-like J774 cells and HT 29 human
      adenocarcinoma cells. Nanocapsules with an external layer made of poly(D,L lactic
      acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG NCs), PLA coated
      with poloxamer 188 (polox PLA NCs) and oil/water nanoemulsion (NE) have been
      examined. The cellular uptake by J774, as determined by microspectroflorimetry,
      is reduced with mTHPC encapsulated into surface-modified NCs--PLA-PEG and polox
      PLA--compared with naked PLA, indicating a possible limitation of the clearance
      of such carriers by the reticuloendothelial system. Encapsulation also modifies
      the interaction between mTHPC and HT29 cells. Compared with the manufacturer's
      solution (PEG, ethanol, water), the cellular uptake is strongly reduced. However,
      the HT29 phototoxicity is much less affected and a protecting effect against
      plasma proteins is observed. Fluorescence microscopy reveals a specific punctate
      fluorescence pattern with PLA-PEG and polox PLA NCs in contrast to a more diffuse
      distribution with NE and solution, indicating that photodamage targeting could be
      different. These findings suggest that photosensitizers encapsulated into surface
      modified nanocapsules could be a promising approach for improving PDT efficacy
      and this has to be confirmed in vivo.

PMID- 10942082
TI  - Protochlorophyllide and chlorophyll forms in dark-grown stems and stem-related
      organs.
AB  - Protochlorophyllide contents and the spectral properties together with
      photoactivities of native protochlorophyllide forms have been studied in dark
      forced stems of 26 and epicotyls or hypocotyls of 9 plant species. The 77 K
      fluorescence emission spectra show that a form emitting at 629-631 nm is general
      in these organs. Besides this short-wavelength form, other protochlorophyllide
      forms emitting at 636, 645 and around 650-655 nm are found with various relative
      amplitudes. The pigment contents show good correlation with the ratio of short-
      to long-wavelength forms, i.e., the higher this ratio is, the less
      protochlorophyllide is detected. In addition to protochlorophyllide, several dark
      grown plants also contain chlorophylls. In some cases only one chlorophyll form
      appears with emission maximum at 678-680 nm; other plants have forms
      characteristic of the fully developed photosynthetic apparatus (with maxima at
      685, 695 and 730-740 nm). Flash illumination can transform only the 645 and 650
      655 nm protochlorophyllide forms, the shorter-wavelength-emitting forms being
      inactive. Plant species with dominating 629-636 nm protochlorophyllide forms
      cannot accumulate chlorophyll on continuous illumination of natural intensity,
      and they became photodamaged. The structural or molecular background of the
      appearance of the different protochlorophyllide and chlorophyll forms and the
      reasons for their photosensitivity are discussed.

PMID- 10942083
TI  - Mycosporine-like amino acids in the marine dinoflagellate Gyrodinium dorsum:
      induction by ultraviolet irradiation.
AB  - Cultures of the marine dinoflagellate Gyrodinium dorsum have been exposed to
      polychromatic radiation (photosynthetically active radiation and UV) from a solar
      simulator for up to 72 h. Different irradiance spectra in the ultraviolet are
      produced by inserting cut-off filters between lamp and samples. The mycosporine
      like amino acid (MAA) content and composition are investigated by spectroscopic
      and chromatographic analysis. The study reveals that G. dorsum contains a complex
      mixture of several aminocyclohexenimine-MAAs and one aminocyclohexenone-MAA. UV
      irradiation around 320 nm induces an increase in the concentration of all MAAs in
      the samples. In contrast, exposure to short-wavelength UV-B radiation results in
      decreased overall MAA production. Furthermore, there is a spectral shift in the
      absorption of the MAA mixture towards shorter wavelengths, indicating that short
      wavelength UV-B induces an altered MAA composition. The amount of MAAs is
      normalized to the chlorophyll a concentration.

PMID- 10942084
TI  - Substituent effects on electrophilicity of flavins: an experimental and semi
      empirical molecular orbital study.
AB  - The reactivities of the triplet excited states of several flavins with different
      N(10)-phenyl substituents have been found to be very similar. There is a good
      correlation between semi-empirical molecular orbital calculations at the
      MINDO/AM1 level and observed redox potentials. However, the most interesting
      observation is that the substituent effects are very small; this suggests that
      the N(10)-phenyl substituents are nearly perpendicular to the plane of the main
      ring due to their steric interactions with the main isoalloxazine system.
      Computed calculations as well as the fact that similar absorption maxima are
      obtained for 3-methyl-10-phenylisoalloxazine and 3-methyl-10-methylisoalloxazine
      are in agreement with this prediction.

PMID- 10942085
TI  - A semiempirical study for the ground and excited states of free-base and zinc
      porphyrin-fullerene dyads.
AB  - The ground and excited states of a covalently linked porphyrin-fullerene dyad in
      both its free-base and zinc forms (D. Kuciauskas et al., J. Phys. Chem. 100
      (1996) 15926) have been investigated by semiempirical methods. The excited-state
      properties are discussed by investigation of the character of the molecular
      orbitals. All frontier MOs are mainly localized on either the donor or the
      acceptor subunit. Thus, the absorption spectra of both systems are best described
      as the sum of the spectra of the single components. The experimentally observed
      spectra are well reproduced by the theoretical computations. Both molecules
      undergo efficient electron transfer in polar but not in apolar solvents. This
      experimental finding is explained theoretically by explicitly considering solvent
      effects. The tenth excited state in the gas phase is of charge-separated
      character where an electron is transferred from the porphyrin donor to the
      fullerene acceptor subunit. This state is stabilized in energy in polar solvents
      due to its large formal dipole moment. The stabilization energy for an apolar
      environment such as benzene is not sufficient to lower this state to become the
      first excited singlet state. Thus, no electron transfer is observed, in agreement
      with experiment. In a polar environment such as acetonitrile, the charge
      separated state becomes the S, state and electron transfer takes place, as
      observed experimentally. The flexible single bond connecting both the donor and
      acceptor subunits allows free rotation by ca. +/- 30 degrees about the optimized
      ground-state conformation. For the charge-separated state this optimized geometry
      has a maximum dipole moment. The geometry of the charge-separated state thus does
      not change relatively to the ground-state conformation. The electron-donating
      properties of porphyrin are enhanced in the zinc derivative due to a reduced
      porphyrin HOMO-LUMO energy gap. This yields a lower energy for the charge
      separated state compared to the free-base dyad.

PMID- 10942086
TI  - Lysozyme photo-oxidation by singlet oxygen: properties of the partially
      inactivated enzyme.
AB  - This work studies the behaviour of partially inactivated lysozyme formed by the
      effect of singlet oxygen, which was obtained through the irradiation of the
      native enzyme solution with polychromatic visible light using Methylene Blue as a
      sensitizer. The polyacrylamide gel analysis of the partially inactivated lysozyme
      solution shows the presence of different protein fractions. One of them, which
      corresponds to 53% of the original enzyme, has the same migration as the native
      enzyme. The others are a mixture of fractions (47%) that show slower migration to
      the cathode. When this experiment is carried out in the presence of sodium
      dodecyl sulfate, only one fraction is obtained, which rules out the presence of
      covalently aggregated forms of lysozyme. The partially inactivated lysozyme has
      lost 74% of the fluorescence emission of the tryptophan (Trp) residues. By using
      the anionic quencher iodide, it is determined that 45 and 36% of the fluorescence
      emission arising from the native and partially inactivated enzyme, respectively,
      are due to Trp residues exposed to the solvent. Michaelis-Menten constants
      (K(in)) of 0.296 and 0.511 (mg/ml) and maximum initial rates (Vmax) of 0.295 and
      0.190 (mg/ml min) are determined for the native and the partially inactivated
      enzyme solutions, respectively. The same inactivation profile is found when the
      denaturing effect of increasing urea concentration on both the native and
      partially inactivated lysozyme is studied. It is postulated that the partially
      inactivated lysozyme solution is composed of one protein fraction with enzymatic
      activity similar to that of the native enzyme and also of a mixture of fractions
      (47% of the total enzyme) with very low activity and characterized by a high
      tryptophan photo-oxidation.

PMID- 10942087
TI  - The role of virion membrane protein endocytosis in the herpesvirus life cycle.
AB  - Endocytosis of cellular surface membrane proteins is a well-characterized, common
      occurrence. Internalization of cell surface receptors, often with bound ligands,
      aid in global events, such as cellular metabolism, as well as in specific,
      directed functions, such as the induction of signal transduction cascades or
      immune function. Some, but not all, herpesvirus membrane proteins are
      internalized from the plasma membrane by a process similar to receptor-mediated
      endocytosis. No known functions, however, have been ascribed to endocytosis of
      these proteins. In this review, we consider the function of herpesvirus membrane
      protein endocytosis. We compare and contrast the endocytosis and intracellular
      trafficking of two pseudorabies virus membrane proteins, the type I glycoprotein,
      gE, and the type II, tail-anchored membrane protein, Us9, and discuss the
      possible function of their internalization during the virus life cycle.

PMID- 10942088
TI  - The predictive value of uvulo-palatoglossal junctional ulcers as an early
      clinical sign of exanthem subitum due to human herpesvirus 6.
AB  - BACKGROUND: The clinical sign of uvulo-palatoglossal junctional (UPJ) ulcers was
      first noted in 1983 in a 5.5-month-old baby with exanthem subitum (ES). An
      earlier prospective clinical study showed that there was a strong association of
      UPJ ulcers and occurrence of ES with a positive predictive value of 95.3% and
      negative predictive value of 100%. OBJECTIVE: To determine the value of uvulo
      palatoglossal junctional (UPJ) ulcers as an early clinical sign of exanthem
      subitum (ES) due to human herpesvirus 6 (HHV 6) infection. STUDY DESIGN: A case
      control study of 20 febrile children with UPJ ulcers versus 26 febrile children
      without UPJ ulcers. These children were followed up for any development of ES and
      investigated for human herpesvirus 6 (HHV 6) as the causative agents of the
      febrile episodes. RESULTS: In this study, 20 out of 46 febrile children aged 3
      months to 3 years with UPJ ulcers were virologically and/or serologically
      confirmed to be due to primary HHV 6 infection. The rest of the 26 children
      without ulcers did not have HHV 6 infection. Of the 20 children with UPJ ulcers,
      only 17 of the 19 children with adequate follow-up till subsidence of fever
      developed ES. None of the 26 children without UPJ ulcers developed ES.
      CONCLUSION: Statistically, there was a significant association of UPJ ulcers as
      an early sign of ES with a positive predictive value of 89.5% and negative
      predictive value of 100%. This finding also suggests that the presence of UPJ
      ulcers is a useful pathognomic clinical sign of symptomatic primary HHV 6
      infection.

PMID- 10942089
TI  - An outbreak of enterovirus 71 infection in Taiwan, 1998. II. Laboratory diagnosis
      and genetic analysis.
AB  - BACKGROUND: An epidemic of enterovirus 71 (EV71) occurred in Taiwan from April to
      December of 1998, with two peaks, one in June and the other in October. Many
      enteroviruses were isolated in our laboratory from 258 cases during this
      outbreak. Approximately half of the enteroviruses isolated were EV71 and one
      fifth were coxsackievirus A16. OBJECTIVES: To analyze laboratory findings in the
      EV71 epidemic of 1998 in Taiwan, various EV71 specimens in different cell lines
      were examined. In addition, genetic analysis of 5' non-coding region (NCR) was
      performed to analyze the strain variation in this outbreak. RESULTS: The
      cytopathic effect induced by EV71 was observed 2-13 (mean of 4.5) days post
      inoculation in Vero cells and 4-15 (mean of 6.6) days in green monkey kidney
      (GMK) cells inoculated with throat swabs. Of the total positive EV71 cases, virus
      was most frequently obtained from throat swabs (91.7%), less from stools (64.8%),
      and none from cerebral spinal fluid (CSF). Molecular analyses of EV71 by
      sequencing the 5' NCR of 34 strains obtained from different clinical categories
      and various geographic areas showed that their sequences differed (0-13 bp in 681
      bp sequenced) by approximately 0-2%. The sequences of these isolates differed
      from EV71 prototype BrCr or MS strain by 17.5-19%, with the exception of two
      samples which exhibited nucleotide variation by only 8.9 and 8.2%, when compared
      to the MS strain. CONCLUSION: EV71 was most frequently isolated from throat swab
      specimens in Vero cells. The molecular analyses of the 5' NCR of EV71 revealed
      that most isolates from this epidemic belonged to a group of closely related
      clones and only two were in a different group which was clustered with the EV71
      MS strain.

PMID- 10942090
TI  - Peripheral CD4+/CD8+ T-lymphocyte counts estimated by an immunocapture method in
      the normal healthy south Indian adults and HIV seropositive individuals.
AB  - BACKGROUND: Flow cytometry is the standard method for the estimation of CD4/CD8
      counts, but the high initial investment for this instrument and costly reagents
      make it unaffordable to most of the centers in a developing country like India.
      OBJECTIVES: To evaluate the feasibility of an alternate system for the estimation
      of CD4 and CD8 counts in normal south Indian adults and validate the usefulness
      of this assay to monitor the counts in HIV seropositive individuals. STUDY
      DESIGN: Forty-six normal healthy adults and 68 HIV seropositive individuals both
      belonging to south Indian linguistic groups were enrolled in this cross-sectional
      study. The HIV seropositive individuals included 54 HIV-1, 9 HIV-2 and 5 HIV 1&2
      infected individuals serologically confirmed by one of the commercial Immunoblot
      kits. The Capcellia CD4/CD8 whole blood assay, an immuno-capture ELISA based kit
      from Sanofi DIAGNOSTICS Pasteur, (France) was used with a few modifications in
      the procedure to measure the CD4 and CD8 counts. RESULTS: The mean CD4 cell
      counts were 1048 (central 95 centile only), 746 and 424 for the normal healthy
      adults, asymptomatic HIV seropositives and symptomatic HIV patients,
      respectively, and the mean CD8 counts were 595, 889 and 732, respectively.
      Statistically significant differences were observed in the CD4 cell counts
      between HIV seronegative healthy adults and asymptomatic (P < 0.001) as well as
      asymptomatic and symptomatic (P < 0.05) HIV infected individuals. The mean CD4
      counts of asymptomatic HIV-2 infected individuals was significantly higher than
      the counts of asymptomatic HIV-1 infected individuals (P < 0.05). CONCLUSIONS:
      This is an user friendly test and can be an alternate to flow cytometry for the
      estimation of peripheral T-lymphocyte subsets in developing countries. The assay
      system has certain limitations inherent to ELISA techniques.

PMID- 10942091
TI  - Detection of sporadic cases of Norwalk-like virus (NLV) and astrovirus infection
      in a single Irish hospital from 1996 to 1998.
AB  - BACKGROUND: 'Norwalk-like viruses' (NLV) and astroviruses are recognised as the
      most important etiologic agents of viral gastroenteritis, excluding rotaviruses.
      However, neither of these two groups of viruses is routinely screened for in
      Irish hospital laboratories. OBJECTIVE: The objective of this study was to
      examine faeces collected from patients with non-bacterial, non-rotaviral
      gastroenteritis and examine if NLVs and astroviruses could be identified as the
      causative agents of the illness. STUDY DESIGN: Faecal specimens were collected
      from a single Irish hospital from February 1996 to June 1998. Three hundred and
      sixty samples were tested for the presence of NLVs using newly designed inosine
      containing degenerate primers. Two hundred and three faecal specimens from
      paediatric patients were screened for the presence of astroviruses. RESULTS: the
      results of the screening study were that 29 (8%) specimens were found to be
      positive for NLV by reverse transcription polymerase chain reaction (RT-PCR) and
      15 (7%) specimens from paediatric patients were found to be positive for
      astroviruses. Genotyping of the NLV-positive samples determined that four of the
      isolates were from genotype I (G1) and 25 were G2. The G2 positive specimens were
      further subtyped by oligonucleotide probing and the majority (n = 21) were found
      to be subtype P2-B, with four isolates being typed as P2-A. No P1-B isolates were
      found. CONCLUSIONS: This is the first report of detection of sporadic cases of
      NLV and astrovirus in Ireland. The results obtained highlight the need for
      continued surveillance of these viruses and the development of rapid detection
      systems for use in clinical laboratories.

PMID- 10942092
TI  - Evaluation of BioStar FLU OIA assay for rapid detection of influenza A and B
      viruses in respiratory specimens.
AB  - BACKGROUND: Demand for the rapid diagnosis of influenza infections has increased
      with the advent of the availability of neuraminidase antiviral therapy for
      influenza A and B. Several rapid assays that detect both influenza A and B are
      now available. OBJECTIVES: In this study we compared the performance of the
      BioStar FLU OIA assay to Bartels Viral Respiratory Screening and Identification
      Kit (Bartels Inc., Issaquah, WA), and cell culture. STUDY DESIGN: A total of 145
      patient specimens for influenza virus detection submitted in either viral
      transport medium or in sterile containers were evaluated by the three methods.
      Specimen types included nasal washings, nasal swabs, sputum, throat swabs, and
      bronchial alveolar lavage (BAL) fluids. RESULTS: Fifty six positive specimens
      were identified based on culture and/or DFA. Of these, 30 specimens were positive
      by the OIA assay for an overall sensitivity of 54%. The OIA assay detected 48% (n
      = 21) of the 44 culture positive specimens and 81% (n = 29) of the 36 DFA
      positive specimens. Eighty six of the 89 culture/DFA negative samples were
      negative by the OIA assay (97% specificity). Analysis of the OIA assay
      sensitivity from samples submitted in M4 transport medium or in sterile
      containers revealed that M4 transport medium does not reduce the sensitivity of
      the OIA assay. Fifteen of the 27 positive samples submitted in M4 transport
      medium were positive by the OIA assay (56% sensitivity) compared to 15 of 29
      positive samples transported in sterile containers (52% sensitivity). Twelve
      specimens were either culture and/or DFA positive for viruses other than
      influenza, but negative by the OIA assay, suggesting that there was no cross
      reactivity of the OIA assay with the other virus types recovered in this study.
      CONCLUSIONS: The overall excellent specificity of the BioStar FLU OIA allows for
      treatment of positive patients for influenza, however, a negative result should
      be confirmed by DFA and culture.

PMID- 10942093
TI  - Human herpesvirus 8 glycoprotein K8.1: expression, post-translational
      modification and localization analyzed by monoclonal antibody.
AB  - BACKGROUND: The genome of human herpesvirus 8 (HHV-8) contains at least 84 open
      reading frames, including the highly immunogenic K8.1. Other studies have
      determined that K8.1 gene generates at least two spliced transcripts in the HHV-8
      infected BCBL-1 cells, termed as glycoprotein (gp)K8.1A and gpK8.1B. OBJECTIVE:
      To analyze the expression, post-translational modification and localization of
      HHV-8 gpK8.1 by monoclonal antibody (mAb). STUDY DESIGN: Mabs to HHV-8 produced
      by conventional hybridization and several clones identified. A mAb was used by
      various immunological assays to analyze HHV-8 K8.1 proteins in BCBL-1- and Sf9
      insect cells. RESULTS: MAb clone 19B4 identified a 0.75-kb insert from the
      lambdaZAP cDNA expression library of 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced BCBL-1 cells. Sequence analysis revealed that the cDNA insert corresponds
      to the published spliced ORF K8.1 mRNA of HHV-8. By immunofluorescence assay, the
      mAb stained the cell membrane, cytoplasm and perinuclear region of TPA induced
      BCBL-1 cells and showed no cross-reactivity with other herpesviruses. By
      immunoblotting assay, mAb 19B4 reacted with two species polypeptides giving a
      diffuse band with rMW from 42 to 64 kDa (gpK8.1A) and two closely migrating
      polypeptides of rMW 35/37 kDa (gpK8.1B). Both species were labeled by
      [14C]glucosamine, indicating that they are glycosylated and only gpK8.1A was
      detected in the virions. Expression of the full length K8.1 derived from cDNA in
      baculovirus system confirmed that these two glycoproteins are encoded by K8.1
      gene. Enzymatic deglycosylation with endoF/peptide-N-glycosidase F, led to the
      reduction of rMW of both polypeptides whereas deglycosylation with O-glycosidase
      led only the reduction of rMW of K8.1A. CONCLUSION: The mAb 19B4 reacts
      specifically with BCBL-1 and Sf9 cells infected with recombinant baculovirus
      containing HHV-8 K8.1 gene. In several assays the mAb reacts with gpK8.1A and
      gpK8.1B. Only the mature spliced gpK8.1A is incorporated into virion. Enzymatic
      deglacosylation determined that gpK8.1A is N- and O-glycosylated, whereas gpK8.1B
      may lack O-glycosylation.

PMID- 10942094
TI  - Sequence analysis of the HIV-1 protease coding region of 18 HIV-1-infected
      patients prior to HAART and possible implications on HAART.
AB  - BACKGROUND: The majority of HIV-infected patients are treated with highly active
      antiretroviral therapy (HAART) consisting of a combination of inhibitors of the
      protease (PIs) and the reverse transcriptase (RTIs). Analysis of mutations within
      these enzymes which are associated with development of resistance to the applied
      inhibitors is of major clinical importance. In particular, pre-existing mutations
      in previously untreated individuals may adversely influence the efficacy of
      HAART. OBJECTIVES: The sequences of the protease coding regions of 18 HIV-1
      infected patients were analysed prior to HAART. STUDY DESIGN: DNA was extracted
      from whole blood samples of HIV-1-infected treatment-naive patients. The protease
      coding region was amplified by nested PCR and sequenced directly. The resulting
      amino acid substitutions were analysed for known mutations associated with known
      resistance to PIs. RESULTS: In all 18 analysed individuals we found 1-10 amino
      acid substitutions per patient in their HIV-1 protease coding region. These
      mutations occurred altogether at 27 positions of the 99 amino acids of the
      protease coding region. Seven of these mutated positions are associated with
      described resistance to PIs. Altogether, 15 of the 18 patients (83%) carried at
      least one such resistance-conferring alteration in their protease coding region.
      All patients are currently followed up during their present therapy to detect
      possible resistance formation to the applied PIs. CONCLUSIONS: A large variety of
      pre-existing mutations associated with resistance to PIs was observed prior to
      their treatment. As none of the patients ever received HAART before and infection
      with resistant viral strains is very unlikely, these amino acid substitutions
      evidently reflect natural polymorphism of the HIV-1 protease coding region.

PMID- 10942095
TI  - Combined endocrine treatment of elderly postmenopausal patients with metastatic
      breast cancer. A randomized trial of tamoxifen vs. tamoxifen + aminoglutethimide
      and hydrocortisone and tamoxifen + fluoxymesterone in women above 65 years of
      age.
AB  - The efficacy of combined endocrine therapy with tamoxifen (TAM),
      aminoglutethimide (AG), and hydrocortisone (H) or tamoxifen and fluoxymesterone
      (FLU) was evaluated against treatment with tamoxifen alone in 311 patients above
      65 years of age with a first recurrence of a metastatic breast cancer. A total of
      279 patients were eligible. The response rates were assessed for 258 fully
      evaluable patients and were the following for the TAM (N = 94), the TAM+AG+H (N =
      83), and the TAM+FLU (N = 81) groups, respectively, PR: 14, 18, and 21%, and CR:
      20, 11, and 23%. The overall response rates are not statistically different (p =
      0.30). The 95% CL of difference in response rates for TAM vs. TAM+AG+H are -9-19%
      and for TAM vs. TAM+FLU -4-25%. Time to treatment failure was comparable with
      median values of 9.2, 7.7, and 9.2 months in the TAM, TAM+AG+H, and TAM + FLU
      group, respectively (p = 0.17). The corresponding figures for survival are median
      times of 22.0, 24.1, and 21.1 months with a p-value of 0.62. Toxicity was more
      pronounced in both the combined treatment groups, and could in most instances be
      attributed to treatment with either AG+H or FLU. Currently, new specific
      aromatase inhibitors with lesser toxicity than AG are being evaluated in
      combination with TAM for treatment of primary and metastatic breast cancer. In
      conclusion, the simultaneous use of TAM and AG +H or FLU does not seem to improve
      the therapeutic efficacy in elderly postmenopausal patients with metastatic
      disease. So far, combined endocrine therapy in this group of patients should only
      be used in the context of clinical trials.

PMID- 10942097
TI  - Breast cancer incidence in relation to smoking cessation.
AB  - High plasma levels of oestrogens are associated with increased breast cancer
      risk. If smoking, as has been suggested, have both a tumour initiating mutagenic
      effect and a protective anti-oestrogenic effect, one would assume that smokers
      who give up smoking have the highest incidence of breast cancer. This was
      evaluated in the follow-up of a cohort of 10,902 women of whom 4,359 were
      premenopausal. Record-linkage with official cancer registries yielded 416
      incident cases during an average follow-up of 13.6 years. The adjusted relative
      risk in all ex-smokers was 1.31 (1.02-1.69), as compared to never smokers, and in
      premenopausal ex-smokers it was 1.57 (1.07-2.30). Breast cancer incidence in
      premenopausal ex-smokers was inversely related to time since cessation, (p for
      trend = 0.01), and was highest among the women who had given-up smoking less than
      12 months before screening: 2.76 (1.55-4.91). There was no significant
      association between current smoking and breast cancer risk. We conclude that
      incidence of breast cancer in premenopausal women who have given up smoking is
      higher than it is in smokers and never smokers. To what extent this may be
      related to endocrine effects associated with smoking cessation remains to be
      evaluated.

PMID- 10942096
TI  - Breast cancer prognostic significance of a single nucleotide polymorphism in the
      proximal androgen response element of the prostate specific antigen gene
      promoter.
AB  - Prostate Specific Antigen (PSA) expression by breast epithelial cells is
      associated with favorable breast cancer prognosis. In preliminary studies, we
      found that a nucleotide variation (G-->A) at position -158 in the androgen
      response element (ARE-1) of the PSA promoter was present in four out of 9 breast
      tumors examined and in a breast carcinoma cell line. We have now determined the
      nucleotide composition at position -158 of DNA extracted from 148 well
      characterized breast tumors and compared tumor genotype with that of controls
      without cancer, with tumor PSA concentration and with clinicopathological
      variables, overall survival and disease free survival. The G-->A base change at
      position -158 is a polymorphism. Allelotypes were similarly distributed in breast
      cancer patients and controls. The Mann-Whitney U Test showed a significantly
      higher tumor PSA concentration in tumors that presented a homozygous G as opposed
      to homozygous A genotype. Genotype at position -158 was not associated with
      clinicopathological variables in contingency table analysis. Univariate Cox
      regression models showed a 28% reduction in risk for death in patients with
      homozygous G genotype compared to those with homozygous A genotype (P = 0.03).
      However, ARE-1 genotype did not significantly add to the prognostic power in the
      multivariate model of overall survival. In summary, the base change at position 
      158 is a polymorphism that may affect breast cancer prognosis, but further
      studies are required to confirm this possibility and to investigate the relevance
      of this polymorphism in terms of breast cancer susceptibility.

PMID- 10942098
TI  - Psychological distress following first recurrence of disease in patients with
      breast cancer: prevalence and risk factors.
AB  - OBJECTIVES: To investigate the prevalence of and risk factors for psychological
      distress following first recurrences of breast cancer. PATIENTS AND METHODS: The
      sample was drawn consecutively from the inpatient and outpatient populations of
      the National Cancer Center Hospital in Japan during an 18-month period from July
      1996 to December 1997. Of the 56 eligible patients, 55 women aged 30-73 year with
      recurrent breast cancer participated in the study. The prevalence of
      psychological distress, including major depressive disorder and adjustment
      disorders was evaluated according to the Structured Clinical Interview for the
      Diagnostic and Statistical Manual of Mental Disorders, Third edition-revised (DSM
      III-R). Risk factors for psychological distress were analyzed with a logistic
      regression model. RESULTS: Of the 55 subjects, 42% met the DSM-III-R criteria for
      major depressive disorder or adjustment disorders. Major depressive disorder was
      seen in 4 (7%), and adjustment disorders in 19 (35%). Logistic regression
      analysis showed that a disease-free interval of less than 24 months significantly
      predicted a diagnosis of major depressive disorder or adjustment disorders (odds
      ratio 5.28, 95% confidence interval; 1.28-21.8, p = 0.02). CONCLUSIONS: These
      results suggest that it is important for all oncology staff to pay careful
      attention to the psychological health of patients who have been informed of their
      cancer recurrence, and that some psychosocial intervention is necessary for
      preventing distress in patients facing early recurrence.

PMID- 10942099
TI  - Pilot studies on the p53 gene in nipple aspirate fluid from patients with breast
      cancer.
AB  - Nipple Aspirate Fluid (NAF) from patients with breast cancer is a potential
      source of exfoliated tumour material amenable to molecular biological study, but
      few such data have been reported. In this study we demonstrate that polymerase
      chain reaction (PCR) amplification of p53 gene DNA is achievable in a proportion
      of NAF samples from breast cancer patients. Subsequently four NAF samples from
      patients whose primary tumours were identified as having a defined p53 mutation
      were studied by single stranded conformational polymorphism analysis (SSCP). Two
      samples yielded PCR product indistinguishable from wild type and two yielded no
      product. Whilst no cancer-related genetic mutations were demonstrated in NAF
      samples, further study is warranted.

PMID- 10942100
TI  - Patients' understanding of their own disease and survival potential in patients
      with metastatic breast cancer.
AB  - PURPOSE: To investigate the effect of understanding their own disease by patients
      with metastatic breast cancer on their survival potential after being informed by
      their physician. PATIENTS AND METHODS: Two hundred and fourteen women with
      metastatic breast cancer who participated in a multi-institutional, randomized
      phase III trial (Japan Clinical Oncology Group (JCOG) Study 8808) were asked
      whether they understood their own disease after being given information about the
      clinical trial. They were classified into two groups on the basis of whether they
      understood or not. We estimated their survival after the time of registration and
      derived relative hazard ratios from Cox's proportional hazards model. RESULTS:
      There were 190 patients in the 'better understanding' group and 24 in the 'poor
      understanding' group. Median survival times after registration were 28.3 and 16.1
      months, respectively. The 'better understanding' group showed a significant
      difference from the 'poor understanding' group (p = 0.016). In multivariate
      regression analysis, patients who did not understand still showed poorer survival
      than those who understood (hazard ratio = 2.09; 95% confidence interval (CI) 1.16
      3.78; p = 0.014). CONCLUSION: These results support the supposition that
      patients' understanding of information about their disease may influence their
      survival. Thus, it is important to evaluate patients' recognition about
      information even after obtaining their consent. However, further investigation is
      needed to clarify the exact nature of this relationship.

PMID- 10942101
TI  - Application of the van nuys prognostic index in a retrospective series of 367
      ductal carcinomas in situ of the breast examined by serial macroscopic
      sectioning: practical considerations.
AB  - The Van Nuys prognostic index (VNPI) was thought to be useful for predicting
      response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS).
      We applied the VNPI under the conditions defined by Silverstein et al., in 367
      retrospective DCIS entirely sectioned into serial macroscopic 2 mm slices (155
      patients had radiotherapy, median follow-up 71 months). The percentage of
      positive blocks with DCIS was also estimated for each specimen with cut-offs at
      30% and 60% to obtain three scores. One hundred and ninety five lesions had a low
      VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local
      recurrences (half invasive, all in the group without radiotherapy) in the low
      VNPI group. The local recurrence rate increased with size (p = 0.001), with
      reduction of distance to margins (p = 0.05), with histologic grade (p = 0.02),
      with percentage of positive blocks (p = 0.0003) and with VNPI score (p = 0.03).
      The percentage of positive blocks was the only independent predictor for local
      recurrence (p = 0.0001). CONCLUSION: (1) The VNPI was a local recurrence rate
      predictor between the low and the intermediate groups but in our series the low
      VNPI group had a surprisingly high local recurrence rate. (2) Only prospective
      studies will assess the importance of margin width and the role of radiotherapy
      in maintaining local control. (3) Estimation of the percentage of positive blocks
      is simple, may be an alternative when measurement of DCIS is difficult and should
      be taken into account.

PMID- 10942102
TI  - A comparison of cell cycle markers in well-differentiated lobular and ductal
      carcinomas.
AB  - Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are
      similar in many respects and their histologic features occasionally overlap.
      Despite the many similarities, some clinical follow-up data and the patterns of
      metastasis suggest that ILC and IDC are biologically distinct. Unfortunately,
      most breast cancer research has focused almost exclusively on the ductal subtype
      or has not stressed the biologic or molecular genetic distinctions between breast
      carcinoma subtypes. Several reports have suggested the possibility that ILCs and
      IDCs differ with respect to expression of antigens involved in proliferation and
      cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation
      of cell cycle related antigens in ILCs, including histologic variants thought to
      represent aggressive neoplasms, and IDCs matched for histologic grade (Modified
      Bloom-Richardson Grade I). We believe that different antigen expression profiles
      could elucidate the biological distinctiveness of breast carcinoma subtypes and
      possibly provide diagnostically relevant information. We studied the expression
      of the following antigens in 28 archived, formalin-fixed ILCs and 34 well
      differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2
      neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs
      expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of
      IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately
      10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of
      ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed
      p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs
      expressed bcl-2. None of the apparent differences were statistically significant.
      The ILC variants demonstrated immunophenotypes that were essentially similar to
      ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show
      similar proliferation and cell cycle control antigen profiles. Despite their
      unusual histologic features, most ILC variants appear to maintain a
      characteristic ILC immunophenotype.

PMID- 10942103
TI  - Improving discussion of surgical treatment options for patients with breast
      cancer: local medical opinion leaders versus audit and performance feedback.
AB  - We studied whether a hospital intervention utilizing medical opinion leaders and
      performance feedback reduced the proportion of women who reported that surgeons
      did not discuss options prior to surgery for early stage breast cancer. Opinion
      leaders provided clinical education to their peers using a variety of strategies
      and were selected for their ability to influence their peers. Performance
      feedback involved distributing performance reports that contained data on the
      outcomes of interest as well as on other treatment patterns. Twenty-eight
      hospitals in Minnesota were randomized to the intervention or to a control group
      that received performance feedback only. The proportion of patients at
      intervention hospitals who said that their surgeon did not discuss options
      decreased significantly (p < 0.001) from 33% to 17%, but a similar decrease was
      observed among control hospitals. Using medical opinion leaders to intervene in
      hospitals appeared as effective as performance feedback.

PMID- 10942104
TI  - Isolated supravalvular aortic stenosis: functional haploinsufficiency of the
      elastin gene as a result of nonsense-mediated decay.
AB  - We have used single-strand conformation and heteroduplex analyses of genomic
      amplimers to identify point mutations within the elastin gene (ELN) in patients
      with non-syndromic supravalvular aortic stenosis (SVAS) from a total of eight
      unrelated families. Six novel point mutations were identified. We have collected
      detailed clinical information on mutation carriers and demonstrated significant
      non-penetrance in some of the families. Together with the new mutations described
      here, 14 point mutations have been reported in SVAS patients, and 10 of these
      result in premature stop codons (PTCs). We have analyzed the expression of ELN
      alleles in skin fibroblasts from one SVAS patient and shown that PTC mutations
      indeed result in selective elimination of mutant transcripts. Inhibition of the
      nonsense-mediated decay mechanism by cycloheximide resulted in the stabilization
      of mutant elastin mRNA. Allelic inactivation by the ELN mutation in this patient
      led to an overall decrease of the steady state levels of elastin mRNA. Finally,
      we have demonstrated reduced synthesis and secretion of tropoelastin by skin
      fibroblasts from the same SVAS patient. We conclude that PTC mutations in ELN
      result in nonsense-mediated decay of mutant mRNA in this patient. Given the
      predominance of PTC mutations in SVAS, we suggest that functional
      haploinsufficiency may be a pathomechanism underlying most cases of non-syndromic
      SVAS.

PMID- 10942105
TI  - The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese
      male workers.
AB  - A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2)
      may influence alcohol-induced liver injury because of higher production of
      acetaldehyde in the liver. In the present study, we examined relationships
      between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among
      Japanese male workers. Study subjects were 385 male workers in a metal plant in
      Japan, who were free from hepatic viruses and did not have higher
      aminotransferase activities (<100). The subjects completed a questionnaire on
      alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined
      by the PCR method followed by restriction-enzyme digestion. In the moderately and
      heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower
      levels than those with ALDH2*1/*1 for all three parameters of liver function,
      whereas no such differences were observed in the least-drinking group. Multiple
      linear-regression analysis, adjusting for age, obesity, and smoking habits,
      revealed that aspartate aminotransferase activity was positively associated with
      alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine
      transferase activity was negatively associated with alcohol intake only in those
      with ALDH2*1/*2. The present study indicates that effects of alcohol intake on
      liver-function biomarkers are likely to be modified by the ALDH2 genotype in
      adult males.

PMID- 10942106
TI  - Exclusion of NFIL3 as the gene causing hereditary sensory neuropathy type I by
      mutation analysis.
AB  - Hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant peripheral
      neuropathy affecting sensory and motor neurons. The disease involves distal
      sensory loss, distal muscle wasting and weakness, and variable neural deafness.
      The HSN1 locus has been mapped to a genetic interval of 3-4 cM on chromosome
      9q22.1-q22.3 and is flanked by markers D9S1781 and FB19B7. This interval contains
      the gene NFIL3, a transcription factor that is regulated by the cytokine IL-3.
      Northern blot analysis of NFIL3 showed a ubiquitously expressed 2.2-kb mRNA.
      Expression was highest in the lung, with lower levels of expression in the brain
      and spinal cord. Mutation analysis by direct sequencing of reverse
      transcription/polymerase chain reaction products from HSN-I patients excluded the
      coding region of the NFIL3 from being involved in the pathogenesis of HSN-I.

PMID- 10942107
TI  - Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in
      spinocerebellar ataxia patients and distribution of CAG repeats at the SCA1, SCA2
      and SCA6 loci in nine ethnic populations of eastern India.
AB  - To identify various subtypes of spinocerebellar ataxias (SCAs) among 57 unrelated
      individuals clinically diagnosed as ataxia patients we analysed the SCA1, SCA2,
      SCA3, SCA6, SCA7 and DRPLA loci for expansion of CAG repeats. We detected CAG
      repeat expansion in 6 patients (10.5%) at the SCA1 locus. Ten of the 57 patients
      (17.5%) had CAG repeat expansion at the SCA2 locus, while four had CAG expansion
      at the SCA3/MJD locus (7%). At the SCA6 locus there was a single patient (1.8%)
      with 21 CAG repeats. We have not detected any patient with expansion in the SCA7
      and DRPLA loci. To test whether the frequencies of the large normal alleles in
      SCA1, SCA2 and SCA6 loci can reflect some light on prevalence of the subtypes of
      SCAs we studied the CAG repeat variation in these loci in nine ethnic sub
      populations of eastern India from which the patients originated. We report here
      that the frequency of large normal alleles (>31 CAG repeats) in SCA1 locus to be
      0.211 of 394 chromosomes studied. We also report that the frequency of large
      normal alleles (>22 CAG repeats) at the SCA2 locus is 0.038 while at the SCA6
      locus frequency of large normal alleles (>13 repeats) is 0.032. We discussed our
      data in light of the distribution of normal alleles and prevalence of SCAs in the
      Japanese and white populations.

PMID- 10942109
TI  - Genomic organisation and chromosomal localisation of two members of the KCND ion
      channel family, KCND2 and KCND3.
AB  - To follow a candidate gene approach for the involvement of the KCND2 and KCND3
      genes (Kv4.2 and Kv4.3) in the pathogenesis of the long QT syndrome (LQTS) and
      Brugada syndrome, it is necessary to determine the genomic organisation of KCND2
      and KCND3. We therefore resolved the intron-exon boundaries and flanking intronic
      sequences and found that KCND2 consisted of six exons and KCND3 of seven exons.
      Subsequently, we designed the oligonucleotide primers needed for amplifying the
      coding exons of both KCND2 and KCND3 and established conditions for polymerase
      chain reaction amplification of each exon from genomic DNA. Furthermore, the
      chromosomal localisation of KCND2 and KCND3 was determined as 7q31 and 1p13.2,
      respectively. This information should facilitate the systematic screening of
      KCND2 and KCND3 exons for mutations in (inherited) arrhythmia syndromes, such as
      LQTS and Brugada.

PMID- 10942108
TI  - Two pregnancies after preimplantation genetic diagnosis for osteogenesis
      imperfecta type I and type IV.
AB  - Osteogenesis imperfecta (OI) is an autosomal dominant genetic disorder
      characterized by the presence of brittle bones and decreased bone mass
      (osteopenia), as a result of mutations in the genes that encode the chains of
      type I collagen, the major protein of bone. The clinical features of the disease
      range from death in the perinatal period to normal life span with minimal
      increase in fractures. The present report describes two polymerase chain reaction
      (PCR)-based assays allowing preimplantation genetic diagnosis (PGD) on the one
      hand for OI type I, the mildest form, and on the other hand for OI type IV, which
      is intermediate in severity between OI type I and OI type III. In the couple
      referred for PGD for OI type I, the female partner carried a 1-bp deletion in
      exon 43 of the COL1A1 gene, resulting in a premature stop codon in exon 46. The
      synthesis of too little type I procollagen results from such a non-functional or
      COL1A1 null allele. In the other couple, referred for PGD for OI type IV, the
      male partner carried a G to A substitution in exon 19 of the COL1A2 gene, which
      results in an abnormal gene product due to an alphaGly247 (GGT) to Ser (AGT)
      substitution (G247S). Both mutations result in the loss of a specific restriction
      enzyme recognition site and can therefore be detected by PCR amplification
      followed by restriction fragment analysis. PCR amplification of genomic DNA of
      the parents-to-be with one of the two primers fluorescently labelled, followed by
      automated laser fluorescence (ALF) gel electrophoresis of the amplified and
      restricted fragments, allowed a distinction between the healthy and affected
      genotypes. PCR on single Epstein-Barr-virus (EBV)-transformed lymphoblasts
      resulted in acceptable amplification efficiencies (87% and 85% for OI type I and
      OI type IV respectively) and the allele drop-out (ADO) rate was assessed at 11.5%
      and 11.1% for OI type I and OI type IV respectively. With research blastomeres,
      100% amplification rates were obtained and no contamination was observed in the
      blank controls, which validated the tests for clinical application. Embryos
      obtained after intracytoplasmic sperm injection (ICSI) were evaluated for the
      presence of the normal genotype of the non-affected parent. For OI type I, two
      frozen-thawed ICSI-PGD cycles and two fresh ICSI-PGD cycles were carried out for
      the same couple. The transfer of two unaffected embryos in the last cycle
      resulted in a twin pregnancy. A twin pregnancy was also achieved in one clinical
      ICSI-PGD cycle for OI type IV.

PMID- 10942110
TI  - Mechanisms of maternal aneuploidy: FISH analysis of oocytes and polar bodies in
      patients undergoing assisted conception.
AB  - We have examined unfertilised oocytes and their first polar bodies (PBs) to
      determine the way in which the frequency of whole chromosome imbalance compares
      with that involving single chromatids and whether the precocious separation of
      chromatids prior to anaphase I affects all pairs of chromosomes. We have applied
      the technique of fluorescent in situ hybridisation in a three-stage method by
      using locus-specific probes for chromosomes 13 and 21 and alpha-satellite probes
      for chromosomes 1, 9, 16, 18 and X to determine the chromosome status of oocytes
      and their PBs. We obtained analysable results from 127 oocytes and 57 PBs from 72
      patients of average age 33 years. Six oocytes and three PBs had extra signals
      but, of these, three were derived from a single patient, aged 26. Anomalies were
      seen in chromosomes 13, 16, 18, X and, notably, 21 but none were observed in
      chromosomes 1 and 9. Half of the anomalies involved additional chromatids rather
      than whole chromosomes. Since particular chromatids were found to be prematurely
      separated in the metaphase II oocyte, this may provide further evidence for an
      additional mechanism of maternal aneuploidy that operates at anaphase II.
      Detailed analyses of both oocytes and PBs have elucidated possible mechanisms
      leading to aneuploid gametes in this group of patients with fertility problems.

PMID- 10942111
TI  - Gene structures of the human non-neuronal monoamine transporters EMT and OCT2.
AB  - Non-neuronal monoamine transporters OCT1, OCT2, and EMT, which are all members of
      the amphiphilic solute facilitator family, control signal transmission by
      removing released transmitters, such as dopamine, noradrenaline, adrenaline, 5
      hydroxytryptamine, and histamine, from the extracellular space. In the current
      study, we have isolated human EMT (gene symbol SLC22A3) and OCT2 (SLC22A2) genes
      and report the gene and promoter organization. Both genes consist of 11 coding
      exons, with consensus GT/AG splice sites and conserved intron locations. The EMT
      gene is 77 kb, and the OCT2 gene is 45 kb in size. For the EMT gene, two
      transcription start points were identified by inverse polymerase chain reaction
      based on mRNA from Caki-1 cells. The EMT promoter, located within a CpG island,
      lacks a consensus TATA box but contains a prototypical initiator element and a
      number of potential binding sites for ubiquitous transcription factors Sp1 and NF
      1. In contrast, the OCT2 promoter is not associated with a CpG island, contains a
      putative TATA box, and potential binding sites for specific transcription
      factors, such as HFH-8 and IK2. Since EMT and OCT2 may play important roles in
      catecholamine homeostasis and, as such, are candidate genes in human disease, the
      present results provide a basis for the analysis of genetic variation and the
      regulation of transcription.

PMID- 10942112
TI  - Confirmation of linkage of Duane's syndrome and refinement of the disease locus
      to an 8.8-cM interval on chromosome 2q31.
AB  - Duane's syndrome is a congenital abnormality of eye movement, which may be
      inherited as an autosomal dominant trait but usually occurs sporadically. Genetic
      mapping in a Mexican family has recently identified a locus for Duane's syndrome
      within a 17.8-cM region of chromosome 2q31. The region was flanked by the
      microsatellite markers D2S2330 and D2S364. We performed linkage and haplotype
      analysis in a four-generation UK family with autosomal dominant transmission of
      Duane's syndrome. Linkage to 2q31 was confirmed with a maximum logarithm of
      differences (lod) score of 3.3 at theta = 0. The genetic interval was reduced to
      an 8.8-cM region between markers D2S326 and D2S364 that includes the candidate
      homeobox D gene cluster.

PMID- 10942113
TI  - Structure and polymorphism of the human gene for the interferon-induced p78
      protein (MX1): evidence of association with alopecia areata in the Down syndrome
      region.
AB  - Alopecia areata (AA) is a chronic inflammatory disease characterised by patchy
      hair loss with T cell infiltration of hair follicles. AA occurs in approximately
      0.1% of the general population, but this is increased to 9% in Down syndrome
      (DS). DS is associated with an additional copy (full or partial) of chromosome
      21, and the DS region may potentially include genes involved in the pathogenesis
      of AA. MX1 is the gene encoding the interferon-induced p78 protein (MxA). MxA
      protein confers resistance to influenza viruses, and we have previously shown
      that MxA protein is strongly expressed in lesional anagen hair bulbs from
      patients with AA but not in normal follicles. We therefore studied the possible
      involvement of MX1 in the pathogenesis of AA. To establish markers in the MX1
      region which could be screened by PCR-based methods, we defined the human MX1
      exon/intron organisation and screened the exons and the introns by conformation
      sensitive gel electrophoresis. We found that the MX1 gene contains 17 exons
      extending over 33 kb. The size and sequence of the region from exon 6 to exon 16
      are highly conserved between human and mouse. Screening of 4747 bp within the MX1
      gene revealed four single nucleotide polymorphisms in intron 6. These
      polymorphisms are concentrated within 147 bp and show strong linkage
      disequilibrium. In a case-control association study for the MX1 (+9959)
      polymorphism in 165 AA patients and 510 controls we found a significant
      association of this marker with AA (odds ratio 1.79, 95% CI 1.21-2.66, chi2 =
      8.464, P = 0.0036). The risk of disease was greater for patchy AA (mild disease)
      and with early age at onset (odds ratio 2.34, 95% CI 1.24-4.43, P = 0.0072),
      providing new evidence of genetic heterogeneity in AA. Our demonstration of
      genetic association between the MX1 gene and disease supports the hypothesis that
      this is a new candidate gene in AA.

PMID- 10942114
TI  - Molecular genetic analysis of severe protein C deficiency.
AB  - Severe protein C deficiency is a rare, early onset, venous thrombotic condition
      that is inherited as an autosomal recessive trait. The protein C (PROC) genes of
      nine unrelated individuals with severe protein C deficiency were sequenced
      yielding a total of 13 different lesions. Eight of these were novel, including a
      gross gene deletion, three missense mutations, two micro-deletions, a splicing
      mutation and a single base-pair substitution in the HNF-3 binding site in the
      PROC gene promoter. Evidence for the pathogenicity of the mutations detected was
      obtained by molecular modelling, in vitro splicing assay and reporter gene assay.
      Neither the plasma protein C activity level nor the nature of the PROC gene
      lesions detected were found to be a good prognostic indicator of the age of onset
      or clinical severity of thrombotic symptoms. Other factors may thus complicate
      the relationship between genotype and clinical phenotype. Indeed, in two
      patients, the inheritance of either one or two Factor V Leiden alleles in
      addition to two PROC gene lesions could have served to precipitate the thrombotic
      events. No association was however apparent between clinical severity and the
      possession of a particular promoter polymorphism genotype. Despite the absence of
      a clear genotype-phenotype relationship, the molecular genetic analysis of the
      severe recessive form of protein C deficiency potentiates both the counselling of
      affected families and the provision of antenatal exclusion diagnosis.

PMID- 10942115
TI  - Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with
      tyrosinemia type III.
AB  - Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by
      the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in
      the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation
      and increased excretion of tyrosine and phenolic metabolites. Only a few cases
      with the disorder have been described, and the clinical spectrum of the disorder
      is unknown. Reported patients have presented with mental retardation or
      neurological symptoms or have been picked up by neonatal screening. We have
      identified four presumed pathogenic mutations (two missense and two nonsense
      mutations) in the HPD gene in three unrelated families encompassing four
      homozygous individuals and one compound heterozygous individual with tyrosinemia
      type III. Furthermore, a number of polymorphic mutations have been identified in
      the HPD gene. No correlation of the severity of the mutation and enzyme
      deficiency and mental function has been found; neither do the recorded tyrosine
      levels correlate with the clinical phenotype.

PMID- 10942116
TI  - Application and evaluation of denaturing HPLC for molecular genetic analysis in
      tuberous sclerosis.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant disorder characterised by the
      development of hamartomas in multiple tissues and organs. TSC exhibits locus
      heterogeneity with genes at 9q34 (TSC1) and 16p13.3 (TSC2) that have 21 and 41
      coding exons, respectively. The mutational spectrum at both loci is wide and
      previous studies have shown that 60%-70% of cases are sporadic and represent new
      mutations. We have formatted denaturing high performance liquid chromatography
      (DHPLC) for rapid screening of all coding exons of TSC1 and TSC2. DHPLC analysis
      detected likely disease-causing mutations in 103 of 150 unrelated cases (68%),
      compared with 92/150 (61%) and 87/150 (58%) for single-strand conformation
      polymorphism analysis (SSCP) and conventional heteroduplex analysis (HA),
      respectively. Capital, consumable and labour costs were determined for each exon
      screening procedure. Estimated costs per patient sample depended on throughput,
      particularly for DHPLC, where a high proportion of costs are fixed, and were
      pounds sterling 257, pound sterling 216 and pound sterling 242 for DHPLC, SSCP
      and HA, respectively, assuming a throughput of 252 samples per year, or pound
      sterling 354, pound sterling 233 and pound sterling 259, assuming a throughput of
      126 samples per year. DHPLC had the advantages of increased sensitivity and
      reduced labour costs when compared with more traditional approaches to exon
      screening but, unless expensive DHPLC equipment is being efficiently utilised for
      a very high proportion of the time available, overall costs are slightly higher.

PMID- 10942117
TI  - Acquired pericentric inversion of chromosome 9 in essential thrombocythemia.

PMID- 10942118
TI  - Gene symbol: VHL. Disease: pancreatic cancer.

PMID- 10942119
TI  - Gene symbol: VHL. Disease: Von-Hippel-Lindau syndrome.

PMID- 10942120
TI  - Reconstruction of nasal defects larger than 1.5 centimeters in diameter.
AB  - OBJECTIVE: To review the repair of larger nasal defects (> 1.5 cm in diameter)
      and the vascular supply to the forehead flap. STUDY DESIGN: Retrospective chart
      review (1994-1999) and cadaver analysis of forehead flap vasculature. METHODS:
      Chart review was made of patients with cutaneous nasal defects greater than 1.5
      cm in diameter. An intravascular silicone cast was used to detail the arterial
      supply to forehead flaps focusing on contribution from the supratrochlear and
      angular vessels. RESULTS: In 127 patients with nasal defects, 76 defects were
      greater than 1.5 cm in diameter and were repaired with a midline forehead flap
      (44 [58%]), paramedian forehead flap (3 [4%]), single-stage midline forehead flap
      (8 [11%]), interpolated melolabial flap (5 [7%]), local nasal flap (7 [9%]), or
      skin graft (9 [12%]). All original defects were modified to some degree with an
      aggressive application of the nasal esthetic subunit principle. Forty-three
      patients (57%) had cartilage grafts, 18 (24%) had a full-thickness defect
      requiring repair of the internal lining, and 11 (14%) had some degree of
      complication, although no patient had full-thickness necrosis of a flap or
      required a second flap. Analysis of the vascular pedicle to the midline and
      paramedian forehead flaps demonstrated significant contributions from the angular
      artery. Skin paddles from a midline and paramedian forehead flap had similar
      vascular arcades. CONCLUSIONS: Nasal reconstruction has reached a standard of
      consistent esthetic results with restoration of nasal function. The midline
      forehead flap is dependable and robust and leaves a donor site scar consistent
      with the principle of esthetic units.

PMID- 10942121
TI  - Genome-wide screening for radiation response factors in head and neck cancer.
AB  - INTRODUCTION: Radiation therapy is an integral part of the treatment of head and
      neck cancer. Factors predicting radiation response are ill defined. The aim of
      this study was to identify genetic aberrations associated with radiation response
      in cell lines derived from head and neck squamous cell carcinomas (HNSCC) using
      comparative genomic hybridization (CGH) for genome-wide screening. METHODS: Five
      cell lines derived from HNSCC were subjected to a single course of radiation (400
      cGy) in parallel with a similarly handled, untreated control. Cellular response
      to radiation was determined on posttreatment days 1, 2, 3, 4, and 5 using a cell
      viability assay (MTT assay). Radiation response was defined as 35% or greater
      decrease in cell survival relative to control. Tumor doubling time was determined
      by cell counts performed at day 0 and 1 for each cell line. All experiments were
      done in quadruplicate. CGH analysis was performed by differentially labeling DNA
      from tumor and normal tissue with fluorescent agents. The labeled DNAs were
      simultaneously hybridized to normal metaphase chromosomes. Image analysis for
      fluorescence intensity along the entire length of each metaphase chromosome
      allowed generation of a color ratio, which was used to detect copy number
      changes. RESULTS: Radioresistance was identified in two of five cell lines. The
      tumor doubling time was not a predictor of radiation response. CGH identified a
      complex pattern of aberrations, with gain of 3q common to all cell lines. The
      number of genetic aberration was higher in radiation-sensitive cell lines than in
      radiation-resistant ones. No recurrent aberrations were unique to the radiation
      resistant cell lines. Recurrent gains at 7p and 17q and losses at 5q, 7q, and 18q
      were unique to the radiation-sensitive cell lines. CONCLUSIONS: The number of
      aberrations identified by CGH analysis may be a predictor of radiation response.
      A large study of primary tumors is warranted to confirm this association and
      identify specific genetic aberrations associated with radiation response.

PMID- 10942122
TI  - Head and neck cancer in cardiothoracic transplant recipients.
AB  - INTRODUCTION: There is an increased incidence of cancer in patients after organ
      transplantation. We reviewed a large series of cardiothoracic transplant
      recipients to determine the incidence and natural history of head and neck
      malignancy. METHODS: A total of 1069 heart (n = 855), heart/lung (n = 111), and
      lung (n = 103) transplants were performed at Stanford University from January
      1968 to February 1998. Demographic data, risk factors, and disease course were
      evaluated in patients who developed cancer. The mean length of follow-up was
      8.9+/-5.2 years. RESULTS: One hundred twenty patients (11.2%) developed 547 non
      lymphomatous malignancies. The mean number of malignancies per cancer patient was
      4.6. The average time from transplantation to development of cancer was 63.1
      months. A total of 50.5% of malignancies presented in the head and neck; 96.4% of
      these were cutaneous in origin and 3.6% were noncutaneous. Of cutaneous
      malignancies, 79.3% were squamous cell carcinoma and 15.9% were basal cell
      carcinoma Cutaneous malignancies most commonly presented on the scalp, cheek,
      lip, and neck. Noncutaneous malignancies involved the oral cavity (5), thyroid
      (4), and parotid (1). Thirteen percent of cutaneous head and neck cancers behaved
      aggressively, requiring extensive management including radical surgery,
      radiation, and/or chemotherapy. A total of 34.2% of cancer patients developed
      metastases and 54.9% of cancer patients died as a direct result of cancer. A
      total of 68% of cancer patients were smokers and 23.8% had significant alcohol
      use. CONCLUSION: Transplant recipients have an increased incidence of cancer
      presenting in the head and neck. Malignancies in transplant patients behave more
      aggressively than in the general population. Recognition of this aggressive
      biological behavior and heightened cancer surveillance should result in improved
      outcomes.

PMID- 10942123
TI  - Esthesioneuroblastoma and sinonasal undifferentiated carcinoma: impact of
      histological grading and clinical staging on survival and prognosis.
AB  - OBJECTIVES: Hyams proposed a histological grading system for
      esthesioneuroblastoma in which grade I tumors have an excellent prognosis and
      grade IV tumors are uniformly fatal. The Hyams grading system predated advanced
      craniofacial techniques, extensive use of immunohistochemistry, and the
      recognition of sinonasal undifferentiated carcinoma (SNUC) as a distinct entity.
      Therefore we aimed to determine whether Hyams classification is useful in
      predicting outcome for esthesioneuroblastoma and SNUC. STUDY DESIGN: A
      retrospective review of cases from 1970 to 1999. METHODS: Twenty-six patients (12
      with esthesioneuroblastoma and 14 with SNUC) were reviewed. The Kadish clinical
      stage was determined, and histopathological slides were reviewed and graded using
      the Hyams system. RESULTS: Kadish staging was available for 26 patients (2
      patients with stage A tumors; 7 with stage B; and 17 with stage C). Of the 8
      evaluable patients with Kadish stage A or B tumors, 6 remained disease free for
      more than 2 years compared with only 5 of the 17 Kadish stage C tumors. Slides
      were available for Hyams grading in 21 patients (2 patients with grade I tumors;
      4 with grade II; 4 with grade III; and 11 with grade IV). Of the 6 patients with
      Hyams grade I or II tumors, 4 remained disease free for more than 2 years
      compared with only 4 of the 15 patients with Hyams grade III or IV tumors. Of
      note, three patients with Kadish stage C tumors (two with esthesioneuroblastoma,
      one with SNUC) and two patients with Hyams grade IV tumors (one with
      esthesioneuroblastoma and one with SNUC) survived for more than 5 years.
      CONCLUSIONS: Both the Hyams grading system and the Kadish staging system can be
      used as independent predictors of outcome. Although limited by small numbers, the
      results of this study demonstrate that patients with either advanced clinical
      stage or pathological grade of esthesioneuroblastoma or SNUC have poor prognosis,
      but that long-term survival is possible in these patients if aggressive treatment
      is used.

PMID- 10942124
TI  - Patterns of swallowing after supraglottic laryngectomy.
AB  - OBJECTIVE: To understand the anatomical and physiological basis for early
      recovery of swallowing function after supraglottic laryngectomy. STUDY DESIGN:
      Retrospective review. METHODS: The records of nine patients who had undergone
      supraglottic laryngectomy at the Stratton Veteran's Administration Hospital
      (Albany, NY) between 1994 and 1998 were reviewed. Videofluoroscopic swallowing
      studies were obtained on all patients as early as was safely possible and were
      reviewed by a multidisciplinary team of physicians, nurses, and speech
      pathologists with regard to anatomical and functional differences between
      successful and unsuccessful recovery of swallowing function. RESULTS: Five of
      nine patients resumed regular diets including thin liquids within 1 year of
      surgery; three patients remained dependent on enteral support. Swallowing success
      was most closely associated with short oropharyngeal transit time and an
      anterosuperior position of the larynx. Laryngeal positioning, tongue base
      mobility, and placement and coordination of the bolus for maximum swallowing
      efficiency can be improved with time and speech therapy. CONCLUSIONS: Factors
      that placed patients at significantly higher risk for aspiration included low
      laryngeal position and delayed oropharyngeal transit time. Tight lingual
      laryngeal closure did not completely prevent aspiration. At the time of the
      initial surgical procedure it may be important to position the laryngeal remnant
      as far superior and anterior under the tongue base as possible.

PMID- 10942125
TI  - The aspiration-irrigation maneuver.
AB  - OBJECTIVES/HYPOTHESIS: To compare cultures obtained from the aspiration
      irrigation maneuver (AIM) with other reports and compare diagnostic and
      therapeutic value after AIM versus the Proetz maneuver and needle aspiration
      irrigation. STUDY DESIGN: Patients with radiographic evidence (mucous membrane
      thickness greater than 6 mm, air-fluid levels, or complete opacification) and
      symptoms (nocturnal cough, fever, postnasal drainage [PND], otitis, mucopurulent
      discharge from the nose) of sinus disease who were referred from pediatrician
      and/or family physician and who otherwise would be candidates for surgery were
      selected to receive treatment with AIM. The study was divided into three separate
      groups (54 patients who were age 8 years and younger, 54 patients who were age 9
      years and older, and 32 adult patients who were treated with both needle
      aspiration and AIM. METHODS: Using Bernoulli's principle and the Venturi effect,
      saline and a vacuum apparatus were used to capture the contents of the sinuses
      for culture, and results were compared with results of needle aspirate cultures.
      RESULTS: Children's cultures from group 1 compared favorably with the literature
      (Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae or a
      combination of these); cultures in patients age 9 years and older revealed a
      greater variety of bacteria, depending on chronicity of infection, and a high
      incidence of Staphylococcus aureus (beta-lactamase positive). There was a 66%
      correlation of AIM with needle aspiration. CONCLUSIONS: AIM was found to be a
      safe, simple, painless, and inexpensive adjunct to the diagnosis and treatment of
      sinus disease.

PMID- 10942126
TI  - Efficacy of computed tomographic image--guided endoscopic sinus surgery in
      residency training programs.
AB  - OBJECTIVE: To determine the efficacy of computed tomographic image-guided
      endoscopic surgery in the hands of inexperienced surgeons. STUDY DESIGN: Four
      second-year otolaryngology residents, with no prior experience performing
      ethmoidectomies, performed endoscopic sinus surgery (ESS) on formalin-fixed human
      cadaveric specimens with and without the aid of computer-assisted surgery (CAS).
      METHODS: Each resident was asked to identify critical sinus, orbital, and skull
      base structures while performing a total ethmoidectomy and multiple sinusotomies.
      Their surgical accuracy (percentage of correctly identified structures), total
      operative time, and incidence of major complications were recorded for each side.
      A total of 16 sides were evaluated (8 with and 8 without CAS). Statistical
      significance between groups was determined by means of Pearson's chi2 analysis.
      RESULTS: Statistical analysis showed a significant difference (P = .001) in the
      mean accuracy of identifying critical anatomical landmarks between the CAS (97%)
      and non-CAS (76.8%) groups. Although not statistically significant, operative
      time appeared to be longer in the group using CAS (average of 67 vs. 80 min).
      Three major intracranial complications were documented only in the group not
      using CAS. CONCLUSIONS: Although, unquestionably, a thorough knowledge of the
      anatomy remains essential for performing ESS, CAS improves surgical accuracy and
      reduces the risk of major intracranial or intraorbital complications for
      residents. In additional, our data suggest that this technology may enhance
      surgical efficiency and improve the learning curve by reducing operative time
      (below one's normal baseline) while maintaining a greater than 90% accuracy in
      identifying critical anatomical landmarks.

PMID- 10942127
TI  - Endoscopic stapled diverticulotomy: treatment of choice for Zenker's
      diverticulum.
AB  - OBJECTIVE: To evaluate the efficacy and safety of endoscopic stapled
      diverticulotomy in the treatment of patients with Zenker's diverticulum. STUDY
      DESIGN: Cohort study. METHODS: Fourteen elderly patients (11 men and 3 women)
      with Zenker's diverticulum were evaluated in a community hospital setting from
      July 1996 to November 1999. Before surgery patients had significant dysphagia,
      regurgitation, cough, or aspiration pneumonia. The common septum between the
      diverticulum and cervical esophagus was visualized with a Weerda
      diverticuloscope. While using videoendoscopic monitoring, the septum was divided
      and the edges simultaneously sealed with a linear endoscopic stapler. Average
      operative time was 31 minutes. RESULTS: The operation was successfully performed
      in 11 of 14 patients. In the three unsuccessful cases, one patient's pouch was
      too small to staple and the other two patients had a septum that was difficult to
      visualize with the diverticuloscope. There was no significant postoperative
      morbidity or mortality. Patients started a liquid diet on the first postoperative
      day and resumed a soft diet a week later. They were usually discharged on the
      first postoperative day. Most patients reported significant improvement with
      resolution of dysphagia and regurgitation. CONCLUSIONS: Compared with the
      traditional open technique, the endoscopic stapled diverticulotomy technique is
      safe, quick, and effective and requires a shorter length of stay in the hospital.
      Therefore it has become our treatment of choice for elderly, high-risk patients
      with a large (>2 cm) hypopharyngeal (Zenker's) diverticulum.

PMID- 10942128
TI  - Temporal approach for resection of juvenile nasopharyngeal angiofibromas.
AB  - OBJECTIVE: To describe a lateral preauricular temporal approach for resection of
      juvenile nasopharyngeal angiofibroma (JNA). STUDY DESIGN: A retrospective review
      of five patients with JNA tumors that were resected by a lateral preauricular
      temporal approach. METHODS: The medical records of five patients who underwent
      resection of JNA tumors via a lateral preauricular temporal approach were
      reviewed, and the following data collected: tumor extent, blood loss, hospital
      stay, and surgical complications. RESULTS: Five patients with JNA tumors had
      resection by a lateral preauricular temporal approach. These tumors ranged from
      relatively limited disease to more extensive intracranial, extradural tumors.
      Using the staging system advocated by Andrews et al., these tumors included
      stages II, IIIa, and IIIb. Four patients (stages II, IIIa, IIIa, and IIIb) who
      underwent primary surgical excision had minimal blood losses and were discharged
      on the first or third postoperative day with minimal transient complications
      (mild trismus, frontal branch paresis, serous effusion, and cheek hypesthesia).
      The remaining patient (stage IIIb) did well after surgery, despite having
      undergone preoperative radiation therapy and sustaining a significant
      intraoperative blood loss. There have been no permanent complications or tumor
      recurrences. CONCLUSIONS: A lateral preauricular temporal approach to the
      nasopharynx and infratemporal fossa provides effective exposure for resection of
      extradural JNA tumors. The advantages of this approach include a straightforward
      route to the site of origin, the absence of facial and palatal incisions, and
      avoidance of a permanent ipsilateral conductive hearing loss.

PMID- 10942129
TI  - Cranioplasty in acoustic neuroma surgery.
AB  - OBJECTIVES: To measure the incidence of postoperative headaches after
      retrosigmoid resections of acoustic neuromas and to evaluate the impact of
      cranioplasty on the prevention and management of these headaches. STUDY DESIGN: A
      prospective evaluation was performed on 30 consecutive patients who underwent a
      cranioplasty after retrosigmoid excision of their acoustic neuroma. The results
      were compared with 30 historical control patients who underwent the same
      procedure but did not have reconstruction with a cranioplasty. The patients were
      evaluated by review of office records and via telephone questionnaire. METHODS:
      One group of patients (30 patients) had no cranioplasty, and the other group of
      30 patients had primary reconstruction with a titanium mesh-acrylic cranioplasty.
      All 60 patients were asked to report on the duration and severity of their
      headaches by means of a standard questionnaire, grading their symptoms on a scale
      of 1 to 4. The data were subjected to chi2 and Student t test statistical
      analyses. RESULTS: New-onset, postoperative headaches occurred in 27% of
      patients, 23% in the cranioplasty group compared with 30% in the group without
      cranioplasty (a difference that was not statistically significant [P = .158]).
      However, there was a statistically significant difference in the severity of the
      headaches (P<.03). The headaches in the cranioplasty group were less severe and
      were not disabling. There were no complications, infections, or extrusions
      related to the cranioplasty. CONCLUSIONS: Cranioplasty has not been able to
      eliminate postoperative headaches. However, the use of cranioplasty has
      significantly decreased the severity of postoperative headaches after
      retrosigmoid excision of acoustic neuromas.

PMID- 10942130
TI  - Intratympanic gentamicin for the treatment of unilateral Meniere's disease.
AB  - OBJECTIVE: To determine the efficacy of intratympanic gentamicin instillation as
      treatment of incapacitating unilateral Meniere's disease, using a predetermined
      regimen with a fixed dose. STUDY DESIGN: A prospective study from a single
      institution between 1988 and 1998. METHODS: One hundred fourteen patients were
      enrolled in this study. Gentamicin (26.7 mg/mL) was administered three times
      daily for 4 consecutive days. The Committee on Hearing and Equilibrium Guidelines
      for Reporting Treatment Results in Meniere's Disease of the American Academy of
      Otolaryngology and Head and Neck Surgery (1985) were used. RESULTS: Comprehensive
      data were available for 90 individuals. Complete control of vertigo was achieved
      in 76 (84.4%), substantial control in 8 (9.0%), limited control in 2 (2.2%), and
      insignificant control in 4 (4.4%) patients. Disability scores at the end of 2
      years were as follows: 76 patients (84.4%) had no disability, 5 (5.6%) had mild
      disability, 2 (22%) had moderate disability, and 7(7.8%) had severe disability.
      Caloric testing responses, as determined using electronystagmography, were as
      follows: 71% of the patients had an absent ice-water response, 16% had a positive
      ice-water response, and in 13% there continued to be present a bithermal
      response. Hearing was worse in 22 patients (25.6%), unchanged in 41 (48.2%), and
      improved in 22 (25.6%). CONCLUSIONS: Intratympanic gentamicin administration
      using this particular protocol is an effective treatment option for patients with
      disabling unilateral Meniere's disease. Hearing loss is a distinct possibility,
      and patients should be advised accordingly.

PMID- 10942131
TI  - Arytenoid adduction combined with Gore-Tex medialization thyroplasty.
AB  - OBJECTIVE: To describe the technique of combined Gore-Tex medialization
      thyroplasty with arytenoid adduction and to determine the long-term vocal outcome
      of patients treated for unilateral vocal cord paralysis with this procedure.
      STUDY DESIGN: A retrospective chart review and patient reevaluation for patients
      treated at The University of Iowa Hospitals and Clinics between May 1995 and June
      1999. METHODS: The review addressed patient demographics, perioperative and long
      term complications, and voice outcomes. Details of the surgical technique are
      provided within the manuscript. RESULTS: Seventy-two Gore-Tex medialization
      procedures were completed. Arytenoid adduction was included in 22 of these
      procedures. This subset of patients was compared with the patients treated with
      Gore-Tex alone. No major postoperative complications occurred in either group.
      Preoperative and postoperative voice and videostroboscopy data were available for
      19 arytenoid adduction patients and 25 Gore-Tex alone patients. On a seven-point
      scale (6 [severely abnormal] --> 0 [normal voice]), the average patient rating of
      voice dysfunction improved from 4.2 to 1.6 (arytenoid adduction) and 4.5 to 2.8
      (Gore-Tex alone). Maximum phonation time improved from 6.9 seconds to 16.7
      seconds in the arytenoid adduction group. Subjective voice assessment employing
      the four-point GRBAS scale (3 [severely abnormal] --> 0 [normal]) identified
      average improvement from an overall grade of 2.1 to 0.8 arytenoid adduction and
      2.2 to 1.5 in the Gore-Tex alone group. Improvement was identified in the vocal
      quality of breathiness from 1.9 to 0.2 (arytenoid adduction) and 1.9 to 0.9 (Gore
      Tex alone). CONCLUSIONS: The combined technique of Gore-Tex medialization
      thyroplasty and arytenoid adduction provide functional results that appear to
      exceed the improvement attained with medialization alone.

PMID- 10942132
TI  - Intratumoral hypericin and KTP laser therapy for transplanted squamous cell
      carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: To test intratumoral photodynamic therapy (IPDT) as a new
      treatment for squamous cell carcinoma in a preclinical tumor model. STUDY DESIGN
      AND METHODS: Human P3 squamous carcinoma cells were transplanted subcutaneously
      in athymic nude mice and allowed to grow into 300- to 500-mm3 tumors. Hypericin
      dye at 1 microg/gm of body weight was injected intratumorally (IT) or
      intravenously (IV). After 4 hours hypericin biodistribution was assessed in
      ethanol extracts from tissues by fluorescence spectroscopy. IPDT also was tested
      by KTP laser fiberoptic insertion in tumors 4 hours after IT dye injection
      compared to KTP532 laser therapy alone (532 nm, 1W, 40-60 J, 0.6-mm fiber).
      RESULTS: Hypericin concentration in tissues was as follows: (IT vs. IV) for
      tumors (3660 vs. 135 ng dye/gm tissue), lung (760 vs. 6345), liver (75 vs. 935),
      blood (65 vs. 480) compared to skin (465 vs. 110) or muscle (335 vs. 80) adjacent
      to the squamous cell tumors. Four hours after dye injection, the tumor exhibited
      bright orange fluorescence when excited by KTP 532-nm green laser light. The IPDT
      treated tumors had a 3.32+/-0.32-mm radius of cell destruction when H&E-stained
      sections were examined compared with 2.5+/-0.38 mm for the laser only control
      group (n = 10, P = .003). CONCLUSIONS: This pilot study indicates laser IPDT with
      hypericin induces a significant increase in tumor necrosis compared with laser
      alone and may be useful as a less invasive adjuvant treatment for recurrent or
      inoperable human squamous cell cancers of the head and neck.

PMID- 10942133
TI  - Preservation of olfaction in anterior skull base surgery.
AB  - OBJECTIVES/HYPOTHESIS: In selected unilateral tumors and defects of the anterior
      skull base, the preservation of contralateral olfaction is achievable through a
      localized subcranial approach without compromising surgical objectives of
      resection or repair. STUDY DESIGN: Description of a functional adaptation of
      anterior skull base surgical techniques through a retrospective patient series.
      METHODS: Nine patients underwent anterior skull base surgery for unilateral
      cribriform plate disease including four malignant and two benign tumors, two
      encephaloceles, and one iatrogenic cribriform injury with cerebrospinal
      rhinorrhea. All nine patients consented to a localized subcranial approach to the
      anterior skull base to preserve the contralateral olfactory nerves. In four
      patients with benign disease a portion of the ipsilateral nerves was additionally
      conserved. Postoperative olfaction was assessed objectively with a commercially
      available smell test. Indications, technique, results, and complications are
      reported and discussed. RESULTS: All patients had eradication of disease with
      preservation of functional olfaction CONCLUSIONS: Conservation of olfaction is
      possible in selected cases of anterior skull base surgery when the lesion is
      unilaterally confined.

PMID- 10942134
TI  - Transforming growth factor-beta type II receptors and smad proteins in follicular
      thyroid tumors.
AB  - OBJECTIVE: Resistance to transforming growth factor (TGF)-beta-mediated cell
      growth inhibition is a well-known pathogenic mechanism in epithelial neoplasia.
      TGF-beta signaling requires normal function of downstream mediators such as TGF
      beta receptors (TbetaRs) and Smad proteins. The goal of this study is to
      investigate the expression of components of the TGF-beta signaling pathway in
      follicular tumors of the thyroid. STUDY DESIGN: Twenty follicular thyroid
      neoplasms were classified as adenomas (11) or minimally invasive follicular
      carcinomas (9) according to current pathological criteria. Protein expression was
      evaluated to identify differences between benign and malignant tumors that could
      be used as an adjunct to histopathological analysis. METHODS: Paraffin-embedded
      tissue sections containing tumor and adjacent nonneoplastic parenchyma were
      analyzed by immunohistochemistry for the expression of TbetaR type II (TbetaR-II)
      and Smad2, Smad4, Smad6, and Smad7. Expression of each protein in the tumor was
      compared with that of the corresponding adjacent nonneoplastic thyroid
      parenchyma. RESULTS: TbetaR-II expression was lost in 78% of the carcinomas. In
      the remaining 22%, TbetaR-II was preserved but Smad2 expression was lost. In all
      conventional adenomas, however, TbetaR-II expression was maintained. Furthermore,
      all tumors with normal expression of all proteins were adenomas. CONCLUSIONS:
      Downregulation of TbetaR-II is a consistent abnormality in follicular carcinomas
      and can be used to differentiate minimally invasive carcinomas from adenomas.
      Also, downregulation of Smad proteins is another mechanism by which carcinomas
      can become independent from TGF-beta-mediated growth inhibition.

PMID- 10942135
TI  - Odontogenic keratocysts: a clinicopathological study in Hong Kong Chinese.
AB  - OBJECTIVE: To analyze the clinicopathological features of odontogenic keratocysts
      in Chinese patients. STUDY DESIGN: Retrospective analysis. METHODS: The clinical
      records and pathological features of odontogenic keratocysts from 69 ethnic Hong
      Kong Chinese patients (40 male and 29 female patients) were reviewed. RESULTS:
      The male-to-female ratio was 1.4:1; patient age ranged from 6 to 69 years with a
      modal peak in the third decade (mean age, 28 y; median age, 23 y). The
      preoperative diagnosis was correct in 78% of the cases and the most common
      misdiagnosis was dentigerous cyst. Sixty-two percent of the cysts were found in
      the mandible, and 38% in the maxilla. Multiple cysts occurred in 9% (including
      three cases of basal cell nevus syndrome). Histologically, 82.6%, 5.8%, and 11.6%
      of the cysts were parakeratinized, orthokeratinized, and mixed types,
      respectively. Patients with multiple cysts all showed parakeratinization. The
      majority (80%) of the cysts were lined by epithelia with a thickness of five to
      eight cells. Surface corrugation, subepithelial split, suprabasal split,
      satellite microcysts, epithelial islands, significant inflammation, hyaline
      bodies, and dystrophic calcification were present in 10%, 81%, 25%, 38%, 42%,
      46%, 7%, and 10% of cysts, respectively. The overall recurrence rate was 240%,
      with a median time for first recurrence of 19 months (range, 1 mo-22 y). Cysts
      showing orthokeratinization or mixed types of keratinization recurred less often
      than parakeratinized cysts. Recurrence had the same type of keratinization as the
      initial cyst. CONCLUSIONS: Pathological examination of keratocysts is important,
      because keratocysts have different clinicopathological features and carry a risk
      for clinical misdiagnosis.

PMID- 10942136
TI  - Microvascular angiogenesis and apoptosis in the survival of free fat grafts.
AB  - OBJECTIVES/HYPOTHESIS: Autologous fat is an ideal material for augmentation in
      plastic surgery because of its minimal tissue reaction and easy availability, but
      its long-term graft survival is somewhat unpredictable. This study was conducted
      to determine how fat grafts get their vascular supply from the recipient bed and
      why they keep reducing in volume and weight. STUDY DESIGN: Experimental study
      using animal models. METHODS: The expression of vascular endothelial growth
      factor (VEGF) in grafted fat tissue was examined by using immunohistochemical
      staining, and apoptotic cell death in the grafted fat was studied by using
      terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-uridine triphosphate
      (dUTP)-biotin nick end-labeling method. Twenty-five Wistar rats were used as
      models of free fat grafts. Fat tissue taken from inguinal fat pads was grafted to
      the back skin with an 18-gauge needle injection. RESULTS: The weight of the
      injected fat was significantly reduced on the 180th day compared with the
      original weight (32% +/- 10%). VEGF+ cells were observed in fibrous connective
      tissue of the grafts on days 7 and 30 but not after day 90. Apoptotic cells were
      also observed on days 7 and 30. CONCLUSIONS: Angiogenic factors including VEGF
      started to revascularize the graft around day 7, and the extent of the
      vasculature was not reduced after the revascularization. In addition to necrosis
      in the graft's early stages, apoptosis induced by many factors in the graft's
      environment is also, at least in part, a cause of long-term volume reduction of
      the fat graft. Thus clinical application of angiogenic factors such as VEGF to
      fat grafts and control of apoptosis may contribute to improvements in fat
      grafting techniques.

PMID- 10942137
TI  - Prognostic significance of p53/bcl-2 co-expression in patients with laryngeal
      squamous cell carcinoma.
AB  - OBJECTIVE: The p53, bcl-2, and bax genes are known to be involved in control of
      cell cycle progression and regulation of apoptotic cell death. Although they are
      frequently altered in laryngeal squamous cell carcinoma, their clinical relevance
      is not yet fully understood. In the present study, individual and combined
      expressions of these genes were related with patient survival as well as with
      proliferative and apoptotic activity. DESIGN: Retrospective study. METHODS:
      Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that
      were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl
      2, and bax protein expression by immunohistochemistry. Apoptotic cells were
      visualized using the nick end labeling method. To assess proliferative activity
      of tumors, mitotic indices were determined. RESULTS: Age of patients, advanced
      disease (stages HI and IV), high mitotic activity, positive bcl-2 expression,
      high level of p53 expression, and p53/bcl-2 co-expression were significantly
      associated with shortened overall survival in univariate analysis. In
      multivariate analysis, only age and p53/bcl-2 co-expression had independent
      prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax
      ratios, were not associated with patient outcome. A significant positive
      correlation was found between apoptotic and mitotic activity. However, protein
      levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of
      tumor cells. CONCLUSIONS: The co-expression of p53/bcl-2 was an independent
      predictor of patient outcome and had a prognostic value superior to both
      parameters considered separately. The rate of apoptosis mainly counterbalanced
      proliferative activity but appeared not to be significantly influenced by p53,
      bcl-2, and bax.

PMID- 10942138
TI  - Molecular pathogenesis in sporadic head and neck paraganglioma.
AB  - HYPOTHESIS: Similar to familial tumors, sporadic head and neck paragangliomas are
      associated with chromosomal deletions at either 11q13 or 11q22-23. BACKGROUND:
      Familial paragangliomas are inherited in an autosomal dominant pattern with
      genomic imprinting of the maternal allele. Genetic studies of familial
      paragangliomas have localized the causative genetic defect to two separate loci:
      11q13.1 and 11q22-23. The molecular pathogenesis of sporadic head and neck
      paragangliomas has not been studied. METHODS: Blood and tumor samples from
      patients with sporadic head and neck paragangliomas were screened for deletions
      on chromosome 11 using DNA microsatellite markers and polymerase chain reaction.
      Polymerase chain reaction-amplified alleles from tumor specimens were compared
      with those from the blood of eight patients. A greater than 50% reduction in band
      intensity (as determined by densitometric analysis) between blood and tumor
      sample was indicative of a chromosomal deletion. RESULTS: Three of the eight
      patients were found to have deletions at chromosome 11q: two at chromosome 11q22
      23 and one at 11q13. CONCLUSIONS: Sporadic head and neck paragangliomas are
      associated with deletions at chromosome 11q13 and 11q22-23. It is thus likely
      that sporadic and familial paragangliomas share a similar molecular pathogenesis.

PMID- 10942139
TI  - Sphenoid marsupialization for chronic sphenoidal sinusitis.
AB  - OBJECTIVES: To review experience with sphenoid marsupialization and describe the
      technique using new instrumentation. STUDY DESIGN: Retrospective review of five
      cases of chronic sphenoid sinusitis that were resistant to standard medical and
      surgical methods, which were treated by sphenoid marsupialization. METHODS:
      Charts were reviewed and patients were interviewed regarding postoperative
      resolution of symptoms. RESULTS: Five cases of recalcitrant sphenoid sinusitis
      were reviewed. All patients had headache before surgery, and two had visual
      disturbance. In follow-up ranging from 1 to 87 months, all were free of symptoms
      related to the sphenoid sinus. CONCLUSIONS: Marsupialization is an effective
      method of exteriorizing a chronically infected sphenoid sinus. The use of
      functional endoscopic sinus surgery instruments and the TAC attachment of the
      Midas Rex drill make this surgery possible.

PMID- 10942140
TI  - Quantitative analysis of eotaxin and RANTES messenger RNA in nasal polyps:
      association of tissue and nasal eosinophils.
AB  - OBJECTIVES/HYPOTHESIS: Nasal polyps develop in the ethmoidal and middle turbinate
      area, often in relation to inflammatory conditions. Their exact etiology and
      pathogenesis are still under debate. Histologically, the polyps are infiltrated
      by a number of inflammatory cells, with eosinophil predominating in most
      specimens. This finding suggests that the nasal polyp is an inflammatory growth
      that is controlled by the local environment. The chemokines eotaxin and RANTES
      (regulated on activation normal T cell expressed and secreted) have been
      postulated to be involved in the recruitment and activation of eosinophils to
      certain inflamed tissues. The purpose of this study was to investigate eotaxin
      and RANTES mRNA expression in nasal polyps and its effect on tissue and nasal
      eosinophils. METHODS: Nasal polyps (917 allergic and 30 nonallergic cases) were
      obtained from endoscopic sinus surgery, and 15 normal inferior turbinates also
      were taken. Immunohistochemical staining for eosinophils and quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) tests for eotaxin and RANTES
      mRNA expression were performed, and the concentration of nasal eosinophil
      cationic protein (ECP) was measured. RESULTS: The amounts of eotaxin mRNA in the
      allergic nasal polyps were 11.4 times higher and the levels in the nonallergic
      polyps were 6.4 times higher than in the normal inferior turbinate. However, the
      RANTES mRNA expression did not show any differences among the three groups.
      Tissue eosinophilia and nasal ECP levels were significantly correlated with
      eotaxin mRNA level but not with RANTES mRNA expression. CONCLUSION: Nasal polyp
      eosinophilic infiltration and activation correlate mainly with increased eotaxin
      gene expression rather than with RANTES expression.

PMID- 10942141
TI  - Neurological consequences of scuba diving with chronic sinusitis.
AB  - Sinus barotrauma from scuba diving is relatively common, usually self-limiting,
      and often the result of transient nasal pathology. We describe serious
      neurological sequelae occurring in two scuba divers who had chronic sinusitis We
      suggest guidelines for evaluating and treating divers who have chronic sinusitis.
      Divers with nasal or sinus pathology should be aware of the potentially serious
      consequences associated with scuba diving even after endoscopic sinus surgery to
      correct this condition.

PMID- 10942142
TI  - Ultracytochemical localization of the NADPH-d activity in the human nasal
      respiratory mucosa in vasomotor rhinitis.
AB  - OBJECTIVES: Description of the ultrastructural localization of nitric oxide
      synthase in the blood vessels of the nasal respiratory mucosa in patients with
      vasomotor rhinitis. STUDY DESIGN: This research was conducted on seven patients-
      men and women, ages 20 to 45 years--suffering from vasomotor rhinitis and who had
      undergone surgical therapy for reduction of the inferior turbinates. METHODS: To
      study the ultrastructural localization of nitric oxide synthase, NADPH-diaphorase
      cytochemistry was employed. Samples of the nasal mucosa were obtained from
      inferior turbinates. RESULTS: The endothelial cells of the arterioles,
      capillaries, venules and cavernous sinuses revealed a distribution of the
      enzymatic activity similar to that found in unaffected subjects. A strong
      enzymatic activity was recognized in the smooth muscle cells of the cavernous
      sinuses. The smooth muscle cells of arterioles and venules were generally found
      to be negative to enzymatic reaction. CONCLUSIONS: This study suggests that the
      vascular disorders of the vasomotor rhinitis depend, at least in part, from
      nitric oxide synthase induction in the smooth muscle cells of the cavernous
      sinuses.

PMID- 10942143
TI  - Botulinum toxin for essential tremor of the voice with multiple anatomical sites
      of tremor: a crossover design study of unilateral versus bilateral injection.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the relative efficacy of unilateral and
      bilateral injections of botulinum toxin injection (BOTOX) in the treatment of
      essential tremor of the voice (ETV). STUDY DESIGN: Prospective open-label
      crossover study. METHODS: Patients referred to the Neurolaryngology Clinic at
      Toronto General Hospital with a diagnosis of ETV were eligible for the study.
      Patients were sequentially assigned to receive BOTOX as either a bilateral 2.5-U
      or a unilateral 15-U electromyography-guided injection, followed by the
      alternative injection 16 to 18 weeks later. Acoustic, aerodynamic, and
      nasopharyngoscopic data were collected approximately 2, 6, 10, and 16 weeks after
      each injection. Patients were asked to provide a perceptual evaluation of BOTOX
      effects at the conclusion of the study. RESULTS: Three of 10 patients
      demonstrated an objective reduction in tremor severity with bilateral injection,
      and 2 of 9 with unilateral injection. However, 8 of 10 patients wished to be re
      injected at the conclusion of the study. A reduction in vocal effort appeared to
      be coincident with reduction in laryngeal airway resistance after BOTOX
      injection. CONCLUSIONS: Using objective acoustic measures, only a small
      proportion of patients achieved benefit from BOTOX injection for ETV. However, a
      majority of patients in our study benefited from a subjective reduction in vocal
      effort that may have been attributable to reduced laryngeal airway resistance.

PMID- 10942144
TI  - In vivo measurements of temporal bone on reconstructed clinical high-resolution
      computed tomography scans.
AB  - PURPOSE: To retrospectively assess the accuracy of measurements of temporal bone
      anatomy made from reconstructed clinical high-resolution computed tomography
      (HRCT) scans. METHODS: Nine HRCT scans were performed on unselected clinical
      cases in which the subjects had a temporal bone study judged to be normal. The
      orbitomeatal line was prescribed for the direct axial sections. Variations in
      head position (rotation at the neck and lateral bending of the neck) were
      corrected by using the software supplied by the manufacturer. All measurements
      were done on standard 1-mm axial sections and axial reconstructions obtained from
      1-mm coronal slices. The images were viewed at 4000 Hounsfield units (HU) window
      width and 1000 HU window level. Measurements (n = 3) made on 1-mm direct axial
      HRCT scans were compared with the measurements made on reconstructed axial HRCT
      images from the same nine patients. These values were also compared with
      published cadaver data. RESULTS: The measurements obtained from axial
      reconstructed and direct HRCT series approximated each other in each of the nine
      individual studies and also fell within the range of published cadaver values.
      They demonstrated the expected normal temporal bone variability between
      individuals. CONCLUSION: Useful anatomic approximations can be measured in vivo
      from reconstructed clinical HRCT images. Pitfalls are improper window settings,
      head tilt, and rotation. This protocol is widely available and can be implemented
      retrospectively from clinical HRCT scans.

PMID- 10942145
TI  - DFNA9 is a progressive audiovestibular dysfunction with a microfibrillar deposit
      in the inner ear.
AB  - OBJECTIVES: Several mutations in the COCH gene were recently identified in
      American and European families with DFNA9, an autosomal dominant progressive
      sensorineural hearing loss with onset in high frequencies. Our preliminary
      vestibular studies in one American family indicated progressive vestibular
      dysfunction. More complete vestibular studies in European families have shown
      vestibular abnormalities in the affected individuals. Our temporal bone studies
      on two families with DFNA9 revealed, in addition to neurosensory degeneration, a
      unique acidophilic deposit in the membranous labyrinths of the affected
      individuals. The purposes of this study were 1) to further investigate the
      vestibular abnormalities in members of one American family for the purposes of
      genotype-phenotype correlation and 2) to investigate the electron microscopic
      structure of the acidophilic deposit to obtain further insights into the
      pathogenesis of DFNA9. STUDY DESIGN: Prospective analysis. METHODS: Extensive
      vestibular testing was performed in some unaffected and affected members of a
      family with DFNA9. One temporal bone was analyzed by electron microscopy of
      celloidin-embedded tissue. RESULTS AND CONCLUSIONS: The findings indicate
      progressive vestibular dysfunction in many of the patients affected with hearing
      loss. Thus, despite different mutations in the COCH gene, the American and
      European families manifest auditory and vestibular dysfunction. Electron
      microscopic analysis shows the spiral ligament to be enriched for a highly
      branched non-banded microfibrillar substance that is decorated with
      glycosaminoglycan granules. Additionally, the spiral ligament lacks the 67-nm
      thick straight periodically banded bundles of type II collagen that are normally
      abundant in this structure. A speculative pathogenetic model is proposed for this
      unique disease and its relationship with other late-onset or adult-onset
      audiovestibular diseases and Meniere's disease is investigated.

PMID- 10942146
TI  - Effectiveness of the particle repositioning maneuver in subtypes of benign
      paroxysmal positional vertigo.
AB  - OBJECTIVES: To assess the efficacy of the particle repositioning maneuver (PRM)
      in patients presenting with idiopathic benign paroxysmal positional vertigo
      (BPPV) compared with those with evidence of additional peripheral
      vestibulopathies. METHODS: Retrospective administration of the Dizziness Handicap
      Inventory (DHI) to 41 patients with primary BPPV and 31 patients with secondary
      BPPV to subjectively evaluate their symptoms before and after the PRM. RESULTS:
      Both groups indicated a marked improvement in symptoms after the PRM. Only two
      patients reported an increase in their symptoms after the PRM and both had
      secondary BPPV. CONCLUSIONS: The PRM was found to be highly effective in all
      forms of BPPV, but careful history and judicious testing may identify patients
      requiring additional intervention to relieve their symptoms.

PMID- 10942147
TI  - Variability of Eustachian tube function: comparison of ears with retraction
      disease and normal middle ears.
AB  - OBJECTIVE: To explore the short-term and longterm variability of tubal opening
      and closing in ears with advanced retractions and in healthy ears. STUDY
      DESIGN/METHODS: Twenty ears with retraction type middle ear disease (R-MED) and
      20 normal ears underwent direct recording of the middle ear pressure during
      repeated forced openings, equalization of +100 daPa and -100 daPa by swallowing,
      Valsalva inflation, and forceful sniffing. Tests were performed twice (separated
      by 30 min) on each of 2 days separated by 3 to 4 months. RESULTS: There was
      considerable intraindividual variability of the forced opening pressure and the
      closing pressure in both groups, within as well as between sessions and test
      days. Although the variability was 1.5 to 2 times higher in ears with retraction
      than in the normal group, mean Po and Pc did not differ between the groups.
      Compared with normal ears, ears with retraction changed more frequently from a
      positive to negative test response, or vice versa, when re-tested after 30
      minutes. Rates of positive response in the equalization and Valsalva tests were
      significantly lower in diseased ears compared with normal ears. CONCLUSIONS:
      Eustachian tube opening and closing functions vary more in ears with retraction
      disease than in normal ears, which is consistent with the variable clinical
      course of R-MED and implies that single tubal function tests have little
      prognostic value on the individual level.

PMID- 10942149
TI  - Closed laryngectomy using the automatic linear stapling device.

PMID- 10942148
TI  - Assessment of gustatory function by means of tasting tablets.
AB  - OBJECTIVE: To develop a simple test for the screening of gustatory function in
      clinical settings. STUDY DESIGN: We tested 101 healthy volunteers (44 male and 57
      female volunteers; mean age, 47 y) with the following gustatory test: the
      substances sucrose (sweet), citric acid (sour), sodium chloride (salty), and
      caffeine (bitter) were presented as tablets (diameter 4 mm) similar to common
      sweetener tablets. For quantitative assessment of whole-mouth gustatory function
      we used six different dosages with dilutions of each tastant in 50% steps. The
      highest dosage could be easily detected (sucrose, 30 mg; citric acid, 3 mg;
      sodium chloride, 2 mg; caffeine, 2 mg), and the lowest concentration was within
      threshold range. METHODS: Twenty-eight tablets (six different dosages of the four
      basic tastes plus four tasteless tablets) were tried in a randomized order. The
      entire test required 15 to 20 minutes. To evaluate the within-subject test-retest
      reliability, sessions were repeated after 1 week. Results were compared with
      those obtained by means of a conventional three-drop, forced-choice procedure
      using the method of ascending limits. RESULTS: Results of the new gustatory test
      were significantly correlated with those obtained using the three-drop, forced
      choice procedure (correlation coefficient [r] = 0.66, P<.001). In general, women
      performed better than men. Furthermore, younger subjects exhibited a
      significantly higher gustatory sensitivity in both tests compared with older
      subjects. CONCLUSIONS: This quantitative test of whole-mouth gustatory function
      is easy to use, can be self-administered, requires little time, and has a long
      shelf-life. It appears to be suited for routine clinical assessment of gustatory
      function.

PMID- 10942150
TI  - Use of the linear stapler for pharyngoesophageal closure after total
      laryngectomy.

PMID- 10942151
TI  - Canal wall window tympanomastoidectomy.

PMID- 10942152
TI  - Preservation of the integrity of the infraorbital nerve in facial translocation.

PMID- 10942153
TI  - Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human
      carotid endarterectomy.
AB  - We sought to test the hypothesis of an antioxidant effect of dipyridamole in vivo
      in a model of cerebral hypoperfusion. Twenty-one patients (65+/-10 years, 11 men)
      undergoing carotid endarterectomy were allocated in two groups (group 1, 10 with
      dipyridamole, 200 mg p.o., 3-4 h before surgery; group II, 11 with placebo) in a
      double-blind placebo-controlled randomized design. Blood was sampled from
      ipsilateral jugular bulb, and plasma vitamin E content was assayed before, after
      15 and 30 min of clamp, and 2 and 10 min after declamping. In 12 of them,
      lipoperoxides were assayed. Vitamin E plasma content decreased significantly in
      group II (rest, 3.71+/-0.22 mmol/mol of cholesterol, 100%) after clamp (91.5% of
      rest, p < 0.01) and remained unchanged during declamping (90.9% of rest, p <
      0.01), but did not change in group I (rest, 3.5+/-0.44 mmol/mol of cholesterol,
      100%) during clamping (99.9% of rest; p = NS) and after declamping (97.6% of
      rest; p = NS). Lipoperoxide concentration did not change in group I (rest, 302+/
      8 a.u.; clamp, 296+/-13 a.u.; p = NS vs. rest; declamp, 304+/-8 a.u.; p = NS vs.
      rest), and increased significantly in group II (rest, 313+/-5 a.u.; clamp, 352+/
      9 a.u.; p < 0.01 vs. rest; declamp, 343+/-6 a.u.; p < 0.05 vs. rest). Cerebral
      oxidative stress associated with human carotid endarterectomy can be attenuated
      by pretreatment with oral dipyridamole.

PMID- 10942154
TI  - Combination therapy with inhaled nitric oxide and intravenous dobutamine during
      pulmonary hypertension in the rabbit.
AB  - Combination therapy with an intravenous inovasodilator and inhaled nitric oxide
      (NO) may be appropriate in patients with pulmonary hypertension and associated
      right ventricular failure. We examined whether dobutamine and inhaled NO would
      have additive pulmonary vasodilator effects in experimental pulmonary
      hypertension. Pulmonary hypertension was produced in anesthetized, mechanically
      ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was
      administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled
      NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular
      resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output
      (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no
      effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so
      that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect
      on systemic hemodynamics. This study suggests that the combination of dobutamine
      and inhaled NO should produce additive pulmonary vasodilation in patients with
      pulmonary hypertension and associated right ventricular dysfunction.

PMID- 10942155
TI  - Interaction between monocytes and vascular smooth muscle cells enhances matrix
      metalloproteinase-1 production.
AB  - Matrix metalloproteinase-1 (MMP-1) plays an important role in atherosclerotic
      plaque rupture. The purpose of this study was to investigate the expression of
      MMP-1 by cell-to-cell interactions between monocytes and vascular smooth muscle
      cells (VSMCs). Human VSMCs and THP-1 cells (human monocytoid cells) were
      cocultured. MMP-1 levels were measured by enzyme-linked immunosorbent assay.
      Collagenolytic activity was determined by fluorescent labeled-collagen digestion.
      Immunohistochemistry was performed to determine which types of cells produce MMP
      1. Adding THP-1 cells to VSMCs markedly increased the MMP-1 levels and activity
      of the culture media. MMP-1 levels were maximal when the cellular ratio of THP-1
      cells/VSMCs was 1.0. Immunohistochemistry revealed that both types of cells in
      the coculture produced MMP-1. Separated coculture experiments showed that both
      direct contact and a soluble factor(s) contributed to MMP-1 production.
      Neutralizing anti-interleukin (IL)-6 and tumor necrosis factor-alpha antibodies
      inhibited coculture conditioned medium-induced MMP-1 production by VSMCs and THP
      1 cells. Protein kinase C inhibitors, tyrosine kinase inhibitors, and a mitogen
      activated protein kinase inhibitor significantly inhibited MMP-1 production by
      cocultures. Direct cell-to-cell interaction between THP-1 cells and VSMCs
      enhanced MMP-1 synthesis in both types of cells. Increased local MMP-1 production
      and activity induced by monocyte-VSMC interaction play an important pathogenic
      role in atherosclerotic plaque rupture.

PMID- 10942157
TI  - Oculohypotensive effect of angiotensin-converting enzyme inhibitors in acute and
      chronic models of glaucoma.
AB  - We have studied the effects of various angiotensin-converting enzyme (ACE)
      inhibitors on intraocular pressure (IOP) of rabbits with experimentally induced
      ocular hypertension and their mechanism of action. Acute ocular hypertension was
      induced by infusion of 5% glucose (15 ml/kg) through marginal ear vein, whereas
      chronic glaucoma was induced by injection of alpha-chymotrypsin into the
      posterior chamber of the eye. IOP was measured by tonometer. All ACE inhibitors
      were instilled topically in the eye in a sterile solution. The effect of ACE
      inhibitors also was studied on serum cholinesterase (true and pseudo) and the
      enzyme ACE in vitro. Enalaprilat, ramiprilat, and fosinopril produced a time
      dependent decrease of IOP in both acute and chronic models of ocular hypertension
      in rabbits. The decrease in IOP was observed for >4 h, and the extent of decrease
      was comparable to that with both pilocarpine and betaxolol. Prodrugs enalapril
      and ramipril failed to produced any change in IOP. Losartan also produced a
      significant decrease in IOP in the chronic model of ocular hypertension in
      rabbits. All the three ACE inhibitors were found to inhibit ACE activity in
      aqueous humor. The enzyme cholinesterase was found to be inhibited by
      enalaprilat, ramiprilat, and fosinopril. However, atropine did not alter the IOP
      lowering effect of enalaprilat in rabbits. Indomethacin pretreatment produced
      slight but significant inhibition of the IOP-lowering effect of enalaprilat in
      rabbits. Our data suggest that ACE inhibitors enalaprilat, ramiprilat, and
      fosinopril produce a significant ocular hypotensive effect in acute and chronic
      models of ocular hypertension in rabbits. Inhibition of ACE in aqueous humor, and
      in ocular tissues, resulting in reduced angiotensin II formation, could be one of
      the major mechanisms responsible for the IOP reduction by ACE inhibitors in
      rabbits.

PMID- 10942156
TI  - Phosphodiesterase type 5 inhibition enhances vasorelaxation caused by
      nitroprusside in guinea pig intact heart and isolated aorta.
AB  - Increased vascular smooth muscle cyclic guanine monophosphate (cGMP) results in
      vascular relaxation. The vascular effects of stimulating cGMP production with 10(
      8)-10(-4) M nitroprusside (NP) and inhibiting cGMP hydrolysis with 10(-8)-10(-4)
      M zaprinast (ZAP), a selective type V inhibitor of cGMP phosphodiesterase (PDE),
      were assessed in isolated guinea pig hearts and aortic rings. Coronary flow (CF)
      IC50 values for NP and ZAP, respectively, were 0.8+/-0.1 x 10(-6) M and 3.6+/-0.1
      x 10(-6) M; for coronary sinus pO2 IC50 values were 0.7+/-0.1 x 10(-6) M and
      3.7+/-0.1 x 10(-6) M. CF increased by 13+/-2% with 10(-6) NP, and by 12+/-2% with
      10(-5) M ZAP; percentage O2 extraction (%O2E) decreased by 17+/-3% with NP and
      28+/-4% with ZAP. Together, 10(-6) M NP + 10(-5) M ZAP augmented the increased in
      CF to 23+/-3% of control, and the decrease in percentage O2 extraction (%O2E) to
      40+/-4% of control. Other cardiac effects of NP and ZAP were minimal. In
      norepinephrine preconstricted aortic rings, the IC50 for relaxation was elicited
      at 0.4+/-0.1 x 10(-6) M NP and 6.1+/-0.1 x 10(-6) M ZAP. NP given with ZAP gave a
      logarithmic relation so that IC50 [NP] = -(57 log10 [ZAP]) + 416; R2 = 0.95. NP,
      3 x 10(-7) M; ZAP, 3 x 10(-6) M; and NP + ZAP combined increased aortic tissue
      cGMP by eight-, nine-, and 15-fold, respectively. Inhibiting cGMP hydrolysis may
      be an effective approach to augment vasorelaxation elicited by cGMP synthesis in
      the heart.

PMID- 10942158
TI  - Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and
      female sex.
AB  - Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean
      normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats
      showed enhanced maximum contractility in response to norepinephrine; impaired
      smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and
      impaired relaxation in response to acetylcholine (ACh), compared with their lean
      counterparts. The abnormalities were similar in male and female cp/cp rats. The
      NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited
      ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The
      inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no
      reduction in maximal relaxation, and was absent in cp/cp females. These effects
      suggest that the relative importance of NO in the endothelial modulation of
      smooth muscle contractility is greater in male rats. The results are consistent
      with a decreased role for endothelial NO in the cp/cp rats of both sexes and a
      reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO
      independent mechanism is not affected in the female cp/cp rats. The relatively
      small differences between males and females in smooth muscle cell and vascular
      function may contribute to sex-related differences in the atherogenesis,
      vasospasm, and ischemic damage associated with the obese insulin-resistant state.

PMID- 10942159
TI  - Nitrotyrosine causes selective vascular endothelial dysfunction and DNA damage.
AB  - Vascular endothelial dysfunction is recognized as a contributor to a wide array
      of cardiovascular disease states, but the initiating events involved are
      incompletely defined. Elevated plasma levels of free 3-nitro-L-tyrosine (3NT,
      biomarker of peroxynitrite formation) have been measured in settings of
      endothelial dysfunction, but its pathologic significance is unknown. We tested
      the hypothesis that clinically demonstrated concentrations of 3NT can induce
      vascular and endothelial dysfunction in vitro. Further studies evaluated
      involvement of DNA fragmentation and/or apoptosis as a potential mechanism.
      Preincubation of rat thoracic aorta segments with 3NT (100, 250 microM) resulted
      in selective, concentration-dependent impairment of acetylcholine (ACH) maximal
      response, with no change in KCL, phenylephrine, nitroprusside, or ACH EC50
      effects (ACH Emax, 53+/-2, 42+/-5, 31+/-2%; Control, 100 microM, 250 microM 3NT).
      Vascular segments treated with 3NT also demonstrated concentration-dependent DNA
      damage, assessed using DNA nick-end labeling techniques (TUNEL staining),
      compared with control (TUNEL-positive nuclei/linear mm: 5.4+/-1.2, 13.7+/-1.2,
      16.9+/-3.2; Control, 100 microM, 250 microM 3NT), which was confined to the
      endothelial layer. Equimolar tyrosine had no significant effects. Frequency of
      positively stained nuclei was statistically correlated to extent of endothelial
      dysfunction (p < 0.01). Free 3NT is apparently more than a benign biomarker in
      vivo, and may contribute to vascular endothelial dysfunction through promotion of
      DNA damage and/or apoptosis.

PMID- 10942160
TI  - Impaired vasodilatation response to amrinone in the forearm of patients with
      congestive heart failure: role of endothelium-derived nitric oxide.
AB  - Recent in vitro experiments have shown that amrinone enhances the release of
      nitric oxide (NO) from the endothelium and induces NO mediated vasodilatation.
      This in vivo study examined whether amrinone causes vasodilatation mediated by
      endothelium-derived NO, and whether this effect is attenuated in patients with
      endothelial dysfunction. Eight patients with congestive heart failure and 10 age-
      and sex-matched healthy volunteers were studied. Forearm blood flow (FBF) was
      measured before and during infusion of drugs of acetylcholine, amrinone, and
      nitroglycerin in incremental doses. After the completion of these measurements,
      100 micromol of N(G)-monomethyl-L-arginine (L-NMMA) was infused intraarterially.
      Thereafter, FBF measurement in response to incremental doses of amrinone was
      repeated. Infusion of incremental doses of amrinone caused a comparable increase
      in amrinone plasma concentration in both groups. Baseline FBF was 3.2+/-0.79
      ml/min/100 ml in controls vs. 2.91+/-0.79 ml/min/100 ml in patients (p = 0.43).
      In both groups, FBF increased in response to acetylcholine, amrinone, and
      nitroglycerin. During infusion of the highest dose of nitroglycerin, FBF was not
      different between the two groups (p = 0.51); however, FBF during infusion of the
      highest doses of acetylcholine and amrinone was significantly less in patients
      than in controls: 9.75+/-2.69 vs. 24.87+/-8.65 ml/min/100 ml (p < 0.001) and
      3.79+/-1.21 vs. 7.15+/-2.06 ml/min/100 ml (p < 0.001), respectively. L-NMMA
      significantly depressed the increase in FBF in response to amrinone in controls,
      but not in patients. In conclusion, the selective PDE III inhibitor, amrinone,
      has endothelium-derived NO-mediated vasodilating effects in addition to direct
      effects. This property may be impaired in patients with endothelial dysfunction.

PMID- 10942161
TI  - 17Beta-estradiol increases intracellular calcium concentration through a short
      term and nongenomic mechanism in rat vascular endothelium in culture.
AB  - 17Beta-estradiol (E2) plays an important role in Ca2+ fluxes in several cell
      types. It has been proposed that some of its effects are of nongenomic origin E2
      at vascular smooth muscle level can block calcium entry through L-type calcium
      channels, this mechanism cannot include vascular endothelial cells (VECs), in
      which increases in the intracellular calcium concentration ([Ca2+]i) are
      necessary to NO synthesis. We used male rat aorta ECs in culture loaded with fura
      2 and a fluorescence imaging system to evaluate the short-term effects of E2 on
      [Ca2+]i kinetics. We explored the participation of the intracellular steroid
      receptor on the effects induced by E2, using tamoxifen (1 microM) and ICI 182,780
      (10 microM). Our results showed that E2 (like bradykinin) induced an increase in
      [Ca2+]i. Such agonist-like effects showed a biphasic curve behavior. The 17beta
      estradiol effects were not modified by the presence of the intracellular
      estradiol-receptor antagonist tamoxifen, but it is blocked in the presence of the
      ICI 182,780. The 17beta-estradiol effects were obtained even with restriction of
      steroid-free diffusion into cells (17beta-estradiol-bovine serum albumin).
      Phospholipase Cbeta activity is involved in these effects, because U-73122, a
      PLCbeta inhibitor, blocked E2 effects. All E2 effects were of rapid onset
      (milliseconds), exerted at the membrane level, and of rapid offset. We conclude
      that estradiol can influence the endothelium physiologic responses through
      effects of nongenomic origin.

PMID- 10942162
TI  - Vasoconstriction to endothelin-1 is blunted in non-insulin-dependent diabetes: a
      dose-response study.
AB  - The haemodynamic hypothesis for the pathogenesis of diabetic microangiopathy
      argues that an initial increase in microvascular blood flow leads to
      microvascular sclerosis and disturbed autoregulation. Endothelin-1 (ET-1) is an
      endothelium-derived vasoconstrictor peptide that contributes to basal vascular
      tone. Impairment of the vasoconstrictor response to ET-1 could result in
      hyperperfusion and subsequent microvascular damage. The purpose of this study was
      to determine whether vascular responses to ET-1 are impaired in patients with non
      insulin-dependent diabetes mellitus (type 2 diabetes). Ten patients with type 2
      diabetes and nine control subjects underwent brachial artery cannulation. Forearm
      blood flow was measured using strain-gauge venous occlusion plethysmography. ET-1
      in three doses of 5, 10, and 20 pmol/min and 0.9% saline placebo was infused in a
      balanced double-blind randomised manner. Vascular smooth muscle function also was
      assessed using sodium nitroprusside. Control subjects showed vasoconstriction to
      ET-1 of 5 (p < 0.05), 10 (p < 0.05), and 20 pmol/min (p < 0.01). In the diabetic
      group, there was no significant response to ET-1 at 5 pmol/min (p > 0.05);
      however, significant vasoconstriction developed at 10 and 20 pmol/min (p < 0.01).
      There was a significant difference in response to ET-1 at 5 pmol/min between the
      diabetic and control groups (p < 0.05). Responses to sodium nitroprusside were
      similar in both groups (p > 0.05). Patients with type 2 diabetes have a blunted
      vasoconstrictor response to ET-1 despite preserved vascular smooth muscle
      function.

PMID- 10942163
TI  - Effects of azimilide on cardiovascular tissues from normo- and hypertensive rats.
AB  - We tested whether azimilide has potential for use in the treatment of heart
      failure. Azimilide, > or =3 x 10(-5) M, had no effect on the quiescent Wistar
      Kyoto (WKY) rat aorta, or mesenteric and intralobar pulmonary arteries. Azimilide
      > or =3 x 10(-5) M relaxed the KCl-contracted aorta and portal vein. Azimilide,
      10(-7)-10(-5) M, prolonged the WKY left ventricular action potential and
      augmented the force of contraction of left ventricle strips from 12- and 22-month
      old WKY rats. Spontaneously hypertensive rats (SHRs), at ages 12 and 22 months,
      are models of cardiac hypertrophy and failure, respectively. The augmentation of
      force with azimilide was similar on 12- and 22-month-old WKY rats and 12-month
      old SHRs but reduced on the 22-month-old SHR left ventricle. Azimilide, 3 x 10(
      6) and 10(-5) M, augmented the force responses of the 22-month-old SHR left
      ventricle by 40 and 50%, respectively. As azimilide is a vasodilator and positive
      inotrope in the rat, and the positive inotropic effect is present in heart
      failure, azimilide should undergo further testing as a positive inotrope for the
      treatment of heart failure.

PMID- 10942164
TI  - Inhibition of the ER-kinase cascade by PD98059 and UO126 counteracts ischemic
      preconditioning in pig myocardium.
AB  - Our previous studies suggested a protective role of the extracellular signal
      regulated kinases (ERKs) cascade in ischemic preconditioning (IP) in the porcine
      heart. To test this hypothesis further, we studied the influence of the novel
      specific inhibitors of mitogen-activated protein kinase kinases (MEK 1/2) PD98059
      (PD) and UO126 (UO) in IP. The substances were infused intramyocardially and UO
      also systemically in anesthetized, ventilated, open-chested, male pigs. The local
      intramyocardial PD and UO infusions occurred before IP and during both
      reperfusion (RP) phases of IP via four pairs of needles (three pairs verum, one
      solvent) into the risk area (RA). The IP design included two cycles of 10-min
      left anterior descending artery (LAD) occlusion and 10 min RP, followed by 40 min
      of occlusion (index ischemia) and of 60 min of RP. Biopsies of the areas of drug
      infusion were taken after the second RP cycle of IP. By Western blot analysis,
      the phosphorylation of ERK 1/2 and of the downstream transcription factor Elk-1
      were measured, and the activities of the ERKs were tested by in gel
      phosphorylation. Only small infarcts were detected in the control group animals
      with the IP period [infarct size (IS), infarct area/risk area; IS, 2.5+/-0.1%].
      Significant wedge-shaped infarcts were seen around the area of the PD and UO
      infusions. The effects of PD and UO were concentration dependent. The maximal
      dose of UO126 (7.5 mg systemically) was associated with an IS of 68.7+/-2.0%. At
      the end of IP, we observed a significant increase in phosphorylation and
      activities of ERKs. PD (50 microM) induced a 50% inhibition of ERK-1 and 56% of
      ERK-2 activities. Phosphorylated ERK-1 and ERK-2 were decreased after
      microinfusion of both PD and UO (50 microM). Microinfusion of 50 microM PD also
      significantly decreased the phosphorylation of Elk-1 (to 59.2+/-8.3% of control
      conditions). We demonstrate for the first time in vivo that the inhibition of
      ERKs by PD and UO results in a complete cancellation of IP.

PMID- 10942165
TI  - Effect of spironolactone and its metabolites on contractile property of isolated
      rat aorta rings.
AB  - Spironolactone and its active metabolites canrenone and potassium canrenoate are
      normally used as antihypertensive drugs. Although they are classified as
      antagonists of aldosterone, their mechanism of action cannot be ascribed solely
      to the regulation of ion transport in the distal tubule of nephrons. Here we have
      evaluated the effects of spironolactone, canrenone, and potassium canrenoate on
      contractile properties of isolated rat aorta rings. Spironolactone (1-300
      microM), canrenone (1-300 microM), and potassium canrenoate (0.01-10 mM), in a
      concentration-dependent manner, relaxed rat aorta rings precontracted with
      phenylephrine (1 microM) or KCl (40 mM). These relaxant effects were not affected
      by prior treatment with either aldosterone (100 microM), glibenclamide (10
      microM), or tetraethylammonium (10 mM), excluding the possibility that these
      drugs can be involved in either the nongenomic effect of aldosterone or on
      activation of potassium channels. Spironolactone and canrenone at concentrations
      of 30 and 100 microM, but not at 10 microM, and potassium canrenoate at
      concentrations of 0.3 and 1 mM, but not at 0.1 mM, significantly inhibited the
      phenylephrine (0.001-3 microM) concentration-response curve. Conversely, all
      tested concentrations of spironolactone (10, 30, and 100 microM), canrenone (10,
      30, and 100 microM), and potassium canrenoate (0.1, 0.3, and 1 mM) significantly
      inhibited the concentration-response curve induced by cumulative concentrations
      of KCI (10-80 mM). Because both phenylephrine- and KCl-induced contractions imply
      an intracellular Ca2+ influx, we suggest that these drugs could act through an
      inhibition of voltage-dependent Ca2+ channels.

PMID- 10942166
TI  - Renal effects of prolonged cyclooxygenase inhibition when angiotensin II levels
      are elevated.
AB  - We examined the renal functional and hemodynamic changes induced by prolonged
      cyclooxygenase (COX) inhibition when angiotensin II levels are elevated during
      several consecutive days. The effects induced by the infusion of either initially
      subpressor or pressor angiotensin II doses (1 and 5 ng/kg/min) were examined in
      dogs with or without the simultaneous infusion of meclofenamate (5
      microg/kg/min). Experiments were performed in conscious permanently instrumented
      dogs. Infusion of the lower angiotensin II dose alone (n = 6) caused a late 12+/
      2% increase in arterial pressure, a 25+/-6% decrease in renal blood flow (RBF),
      and a transitory decrease in urinary sodium excretion. COX inhibition reduced the
      hypertension and renal vasoconstriction, but enhanced the sodium retention,
      induced by the lower dose angiotensin II infusion (n = 6). The higher angiotensin
      II dose (n = 6) caused a 25+/-4% increase in arterial pressure, a 24+/-5%
      decrease in RBF, and a transitory decrease in urinary sodium excretion. Finally,
      COX inhibition did not modify the renal effects elicited by the higher
      angiotensin II dose (n = 6). The results of this study suggest that endogenous
      prostaglandins play an important role in the regulation of the renal and systemic
      changes induced by prolonged administration of initially subpressor angiotensin
      II doses. It has also been demonstrated that prolonged COX inhibition does not
      modify the renal functional and hemodynamic changes elicited by the long-term
      infusion of a pressor angiotensin II dose.

PMID- 10942167
TI  - Estrogen increases eNOS and NOx release in human coronary artery endothelium.
AB  - Estrogen protects against the development of coronary heart disease in women.
      This study was designed to examine the direct effects of estrogen on nitric oxide
      release and endothelial nitric oxide synthase (eNOS) expression in cultured human
      coronary artery endothelial cells (HCAECs). NOx (nitrate, nitrite, and nitric
      oxide) was measured by the chemiluminescence method. Prolonged treatment (48 h)
      of the cells with 17beta-estradiol (E2beta), but not 17alpha-estradiol (E2alpha),
      resulted in a 2.3-fold increase in basal NOx release in HCAECs and an enhanced
      adenosine triphosphate (ATP)- and calcium ionophore A23187-induced NOx release.
      The effects of E2beta on endothelial NOx release were blocked by estrogen
      receptor antagonist ICI 182,780. E2beta had no effect on basal and ATP-stimulated
      intracellular Ca2+ concentrations in HCAECs. However, E2beta significantly
      increased eNOS protein levels, as determined by Western analysis. We conclude
      that estrogen increases NOx release in HCAECs, which is independent of cytosolic
      Ca2+ mobilization and is mediated by the upregulation of eNOS.

PMID- 10942168
TI  - Simvastatin acts synergistically with ACE inhibitors or amlodipine to decrease
      oxygen consumption in rat hearts.
AB  - Statin drugs, which are cholesterol-lowering agents, can upregulate endothelial
      nitric oxide synthase (eNOS) in isolated endothelial cells independent of lipid
      lowering. We investigated the effect of short-term simvastatin administration on
      NO-mediated regulation of myocardial oxygen consumption (MV(O2)) in tissue from
      rat hearts. Male Wistar rats were divided into (a) control group (n = 14), and
      (b) simvastatin group (n = 10, 20 mg/kg/day by oral gavage). After 2 weeks, left
      ventricular myocardium was isolated to measure MV(O2) using a Clark-type oxygen
      electrode, and aortic plasma nitrates and nitrites (NOx) were measured. Baseline
      plasma NOx levels (19+/-2.6 in control vs. 20+/-2.5 microM/L in simvastatin) and
      baseline MV(O2) (288+/-23 in control vs. 252+/-11 nmol/g/min; p = 0.09) were not
      significantly different between the two groups. NO-dependent regulation of MV(O2)
      in response to bradykinin, ramipril, or amlodipine was augmented in simvastatin
      rats compared with controls (p < 0.05). Decrease of MV(O2) from baseline in
      response to highest doses in control versus simvastatin groups was as follows
      bradykinin, -28+/-5% vs. -44+/-6%; ramipril, -35+/-5% vs. -50+/-8%; and
      amlodipine, -32+/-9% vs. -42+/-3%. Response to highest dose of NO donor S-nitroso
      N-acetyl penicillamine (SNAP) was not significantly different in the two groups (
      55+/-5% vs. -52+/-7%). Treatment with Nw-nitro-L-arginine methyl ester, inhibitor
      of NO synthesis, attenuated the effect of bradykinin, ramipril, and amlodipine on
      MV(O2) (p < 0.05). In conclusion, short-term administration of simvastatin in
      rats potentiates the ability of angiotensin-converting enzyme (ACE) inhibitors
      and amlodipine to cause NO-mediated regulation of MV(O2).

PMID- 10942169
TI  - Treatment with acarbose may improve endothelial dysfunction in streptozotocin
      induced diabetic rats.
AB  - We sought to determine whether a single reduction of hyperglycemia and those
      derivatives from nonenzymatic protein glycosylation may be effective in reducing
      the development of diabetic endothelial dysfunction. Therefore, we investigated
      how acarbose, an inhibitor of intestinal alpha-glucosidase that reduce
      hyperglycemia by lowering glucose absorption, may prevent the impairment of
      acetylcholine (ACh)-induced endothelium-dependent relaxations observed in
      isolated vascular segments from untreated streptozotocin-induced diabetic rats.
      When administered after diabetes induction, 10 mg/kg acarbose decreased modestly
      the enhancement of blood glucose and glycosylated hemoglobin (HbA1c) levels, but
      not those of advanced glycosylation end products (AGEs). This effect was linked
      to a partial improvement of ACh-induced responses both in conductance vessels,
      such as aortic segments, and resistance vasculature, like mesenteric
      microvessels. When acarbose was introduced after 6 weeks of untreated diabetes,
      blood glucose, HbA1c, and AGE levels were not affected and endothelial
      dysfunction remained unchanged in mesenteric microvessels, whereas a small
      improvement was observed in aortic segments. The addition of 100 U/ml superoxide
      dismutase enhanced the impaired relaxations to values similar to vessels from
      nondiabetic rats, indicating a main role for superoxide anions in diabetes
      induced endothelial dysfunction. We conclude that hyperglycemia itself or
      elevated HbA1c, but not plasma AGEs, are related to enhanced oxidative stress and
      to the impairment of endothelium function associated to diabetes. This process
      can be partially prevented by reducing glucose absorption with acarbose.

PMID- 10942170
TI  - Potentiating effects on contractions by purified baicalin and baicalein in the
      rat mesenteric artery.
AB  - The effects of purified baicalin and baicalein from the traditional Chinese herb,
      Huangqin, on contractions induced by phenylephrine, U46619, and high
      extracellular K+ were investigated in isolated rat mesenteric arteries. Both
      baicalin (1-100 microM) and baicalein (1-50 microM) potentiated the contractile
      response to phenylephrine in a concentration-related manner. Both flavonoids (10
      microM) also enhanced the U46619- or 40 mM K+-induced contractions. Baicalein
      (100-300 microM) reduced the phenylephrine-induced tone. Prazosin at 1 microM did
      not affect U46619-induced contraction in the absence and presence of baicalein or
      baicalin. Neither baicalin (1-100 microM) nor baicalein (1-100 microM) affected
      the basal tension. Removal of the functional endothelium abolished the
      potentiating effects of baicalin and baicalein in arteries preconstricted by both
      constrictors. Pretreatment of endothelium-intact rings with 100 microM N(G)-nitro
      L-arginine also potentiated phenylephrine- or U46619-induced contraction but
      completely inhibited the effects of baicalin and baicalein. Pretreatment with 1
      mM L-arginine reversed the enhancing effect of baicalin but not of baicalein on
      phenylephrine-evoked contraction. Pretreatment with 10 microM baicalin or 10
      microM baicalein significantly reduced the endothelium-dependent relaxation
      induced by acetylcholine or ionomycin. These results indicate that both baicalin
      and baicalein potentiated the evoked contractile response, likely through
      inhibition of nitric oxide formation and/or release in the endothelium.

PMID- 10942171
TI  - Minoxidil inhibits proliferation and migration of cultured vascular smooth muscle
      cells and neointimal formation after balloon catheter injury.
AB  - The goal of the study was to investigate the in vitro and in vivo inhibition of
      minoxidil on smooth muscle cell (SMC) proliferation and migration as well as
      neointimal formation. The in vitro effect of minoxidil was investigated by Boyden
      chamber assay and cell-cycle analysis. To evaluate the in vivo effect, we treated
      the animals with minoxidil in their drinking water before and after balloon
      catheter injury to carotid artery. Results showed that minoxidil inhibited SMC
      migration across type I collagen membrane in a dose-related manner (13.5% by 0.01
      mg/ml; p < 0.05; 16.8% by 0.05 mg/ml: p < 0.01; 40.4% by 0.25 mg/ml; p < 0.001;
      and 65.8% by 1.25 mg/ml; p < 0.001). Minoxidil (0.8 mg/ml) increased the number
      of SMCs in G1 phase (p < 0.05) and decreased the number of SMCs in S phase (p <
      0.001). In vivo minoxidil treatment reduced neointimal mass by 31.7% (120 mg/L)
      and 42.3% (200 mg/L), respectively. Data demonstrate that minoxidil inhibits
      vascular SMC proliferation and migration both in vitro and in vivo, and therefore
      may be useful to inhibit SMC hyperplasia that occurs in restenosis and other
      vascular diseases.

PMID- 10942172
TI  - A comparison of carvedilol and metoprolol antioxidant activities in vitro.
AB  - Carvedilol is a vasodilating beta-blocker and antioxidant approved for treatment
      of mild to moderate hypertension. angina, and congestive heart failure.
      Metoprolol is a beta1-selective adrenoceptor antagonist. When carvedilol and
      metoprolol were recently compared in clinical trials for heart failure, each
      showed beneficial beta-blocker effects such as improved symptoms, quality of
      life, exercise tolerance, and ejection fraction, with no between-group
      differences. When thiobarbituric acid reactive substance (TBARS) levels were
      measured in serum as an indirect marker of free radical activity, there were also
      no between-group differences. However, we had noted superior cardioprotection by
      carvedilol in comparison to metoprolol in ischemia and reperfusion models. We
      therefore examined antioxidant activity directly in cells and tissues. Here we
      show that in cultured rat cerebellar neurons, and in brain and heart membranes,
      carvedilol has far greater antioxidant activity than metoprolol, which is
      essentially inactive as an antioxidant in these model systems. The antioxidant
      activity of carvedilol could be explained by a greater degree of lipophilicity,
      as measured by its ClogP value of 3.841 as contrasted to a ClogP value of 1.346
      for metoprolol. Alternatively, the molecular structure of carvedilol favors redox
      recycling, which the structure of metoprolol does not. Therefore, carvedilol
      could have additional pharmacologic effects that are favorable for long-term
      therapy.

PMID- 10942173
TI  - The monoethylglycinexylidide test does not impair psychometric performance in
      patients with chronic hepatitis or cirrhosis.
AB  - Lidocaine (LID) is an aminoethylamide used in hepatology to perform the
      monoethylglycinexylidide (MEGX) test for the evaluation of liver function in
      patients with cirrhosis (CIR) or chronic hepatitis (CH). The authors evaluated
      whether the MEGX test changes psychometric performance in patients with chronic
      liver disease and, in particular, whether it might trigger subclinical
      portosystemic encephalopathy in patients with CIR. Thirty patients with CIR and
      20 patients with CH were studied. They underwent a standard-dose MEGX test,
      before and after which a psychometric test was administered and blood pressure,
      heart rate, and adverse effects were recorded. The MEGX test did not modify
      psychometric performance. Mean arterial blood pressure and heart rate did not
      change at the end of the MEGX test in either patients with CH or CIR. Adverse
      effects were present in 66% of all patients during lidocaine injection and lasted
      up to 3 minutes afterwards. They were more frequent in patients with CH than in
      patients with CIR (85% vs 53%). No relationship was found between adverse effects
      and lidocaine dosage, nor between adverse effects and MEGX or lidocaine
      concentration at 15 minutes. Standard-dose MEGX test does not worsen or trigger
      portosystemic encephalopathy in CIR. Adverse effects were frequent but mild.

PMID- 10942174
TI  - Variable correlation between 6-mercaptopurine metabolites in erythrocytes and
      hematologic toxicity: implications for drug monitoring in children with acute
      lymphoblastic leukemia.
AB  - Nineteen pediatric patients affected by acute lymphoblastic leukemia (ALL) were
      examined weekly with respect to 6-mercaptopurine nucleotide (6-MPN) and 6
      thioguanine nucleotide (6-TGN) levels in erythrocytes during the course of
      maintenance treatment with 6-MP 50 mg/m2 per d and results were related to
      various parameters of bone marrow function to assess, in the same individual, the
      level of reliability of 6-MP metabolites in predicting a later change in
      peripheral blood cell counts. Median values for 6-MPN and 6-TGN were 57 and 200
      pmol/8 x 10(8) erythrocytes, respectively, as measured by reversed-phase high
      performance liquid chromatography (HPLC). 6-TGN levels in erythrocytes were
      inversely related with white blood cell count (r = -0.463, p < 0.0001, n = 361),
      absolute neutrophil count (r = -0.386, p < 0.0001, n = 347), erythrocyte (r = 
      0.354, p < 0.0001, n = 287), and platelet counts (r = -0.24, p < 0.0001, n = 319)
      in the majority of patients (n = 10-12), while no correlation was found for 6
      MPN. In the remaining children, no evidence of correlation was demonstrated
      between 6-TGN levels and myelotoxicity. The results confirm the role of 6-TGN as
      the reference cytotoxic metabolite for evaluating the exposure to 6-MP and
      identifying treatment compliance in ALL children but indicate the limits of a
      follow-up based solely on metabolite levels and suggest that a more correct
      approach remains the double monitoring of 6-TGN and blood cell count with
      differential.

PMID- 10942175
TI  - Ketobemidone may alter busulfan pharmacokinetics during high-dose therapy.
AB  - The authors report a possible interaction between ketobemidone and busulfan
      during myeloablative treatment of a patient with acute myeloid leukemia. At the
      time of admission, the patient was receiving ketobemidone 1,000 mg/d as analgesic
      for a rectal fissure. The patient started conditioning prior to bone marrow
      transplantation with busulfan (1 mg/kg x 4 for 4 days). High busulfan plasma
      concentrations were observed after the first dose and the next doses were reduced
      to 0.7 mg/kg. The kinetics of both drugs revealed that an increase in
      ketobemidone concentration was followed by an increase in busulfan levels.
      Substituting ketobemidone with morphine resulted in a decrease in busulfan
      concentration despite increasing the dose once more to 1 mg/kg.

PMID- 10942176
TI  - Ciprofloxacin disposition in elderly patients with LRTI being treated with
      sequential therapy (200 mg intravenously twice daily followed by 500 mg per os
      twice daily): comparative pharmacokinetics and the role of therapeutic drug
      monitoring.
AB  - Ciprofloxacin is a fluoroquinolone antibiotic effective in the treatment of lower
      respiratory tract infections (LRTI). The aim of this study was to assess the
      pharmacokinetic appropriateness of a standard switch i.v./os regimen of
      ciprofloxacin (200 mg i.v. bid for 3 to 5 days followed by 500 mg os bid for 7 to
      10 days) frequently used in routine clinical practice in the treatment of elderly
      patients with mild to moderate LRTI. The pharmacokinetic study was performed on a
      cohort of 17 elderly inpatients. Blood samples were collected in steady state
      conditions at appropriate intervals. Ciprofloxacin serum concentrations were
      analyzed using an HPLC method and pharmacokinetic parameters were estimated using
      the WinNonlin software package. The pharmacokinetic data were at least partially
      different from those obtained by other authors in elderly patients (lower Cmax
      after i.v. administration and higher CL both after i.v. and oral administration).
      Cmax after a 1-hour 200-mg infusion were similar to those observed during the 500
      mg bid peroral regimen (2.1 +/- 0.9 mg/L vs 2.6 +/- 1.0 mg/L; p = 0.054). The
      absolute oral bioavailability (84.1%) allowed a total body exposure 2.1-fold
      greater after 500 mg bid oral administration than after 200 mg bid i.v.
      administration (AUC(0-tau) 11.4 +/- 4.3 mg/L x h vs 5.5 +/- 1.8 mg/L x h). The
      results show that in malabsorption-free elderly patients a regimen of 500 mg os
      bid may be considered a valid therapeutic approach from the beginning of therapy
      for mild to moderate LRTI caused by sensitive microorganisms (MIC < 0.1 mg/L). In
      fact, because the peak serum level to MIC ratio (Cmax/MIC) and the area under the
      inhibitory serum concentration-time curve (AUIC24 = AUC24h/MIC) are actually
      considered major pharmacodynamic determinants for the outcome of treatment with
      fluoroquinolones, this regimen could guarantee both a better pharmacokinetic
      exposure than the 200 mg i.v. bid regimen and a cost-effective treatment of LRTI.
      However, because of the great pharmacokinetic interindividual variability
      observed a normalized dosage per kg (3 mg/kg/12h i.v. and 8 mg/kg/12h os) should
      be considered, especially for body weight >90 kg and, whenever possible, TDM of
      AUC(0-tau) or at least of Cmax should be performed to individualize therapy in
      this subpopulation.

PMID- 10942177
TI  - CYP2D6*10 alleles are not the determinant of the plasma haloperidol
      concentrations in Asian patients.
AB  - The authors we investigated the relationship between plasma levels of haloperidol
      (HAL) and the number of CYP2D6*10 (*10) alleles in 66 Japanese inpatients with
      schizophrenia (male = 61, female = 5) on HAL. Plasma HAL level was determined by
      an enzyme immunoassay method. Daily dose of HAL was 1.5-36 (mean +/- SD = 12.3 +/
      7.6) mg or 0.02-0.49 (0.21 +/- 0.13) mg/kg body weight. Plasma HAL levels ranged
      from 1.4 to 47.4 (12.4 +/- 9.5) ng/mL. No significant difference in the plasma
      HAL levels was observed between the subjects with no, one, and two *10 alleles
      (one-way analysis of variance: 56.1 +/- 20.3, 61.0 +/- 20.3, and 63.3 +/- 20.3
      ng/mL/mg/kg, respectively, F(2,63) = 0.65, p = 0.52). These results are not
      supportive of the previous report that plasma HAL levels can be predicted by the
      number of *10 alleles in Asian patients.

PMID- 10942178
TI  - Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme
      activity.
AB  - Thioridazine is metabolized in humans by CYP2D6 to mesoridazine, which is an
      active metabolite. Two or more CYP2D6 substrates are seldom given simultaneously
      to elderly patients because potentially dangerous metabolic interactions may
      occur. It may be valuable to know the CYP2D6 metabolic capacity of such patients
      to avoid drug interactions, which depend on the metabolic phenotype. The goal of
      this study was to evaluate the use of the mesoridazine/thioridazine ratio for the
      estimation of CYP2D6 enzyme capacity. A sensitive and reliable method has been
      developed for the determination of thioridazine and its metabolites, mesoridazine
      and sulforidazine. Commonly used central nervous system (CNS) comedications do
      not interfere with the method. A group of 27 chronic patients with mental illness
      receiving monotherapy with thioridazine were studied. There were 23 men and 4
      women between 37 and 80 years old (mean +/- SD: 61.2 +/- 10.2). The
      thioridazine/mesoridazine ratio correlated with the debrisoquine metabolic ratio
      (r = 0.74, p < 0.001). Therefore, the authors suggest that the measurement of
      thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity
      during treatment.

PMID- 10942179
TI  - Relationship between efficacy, tolerance, and plasma drug concentration of
      ritonavir in children with advanced HIV infection.
AB  - The relationship between ritonavir plasma concentration, efficacy, and tolerance
      was evaluated in 31 children with advanced HIV infection who were receiving a
      triple therapy with ritonavir as protease inhibitor. Median CD4+ lymphocyte count
      and median viral load before the initiation of ritonavir-containing combination
      therapy were 1320 cells/mL and 5 log10 copies/mL, respectively. Ritonavir was
      given at a dose ranging from 300 to 450 mg/m2 twice daily. The median follow-up
      of triple therapy was 19 months. Response was defined as a drop of viremia of
      more than 1 log. Plasma drug levels were determined twice during the observation
      period: after at least 4 weeks and after 3 months of combined treatment. Samples
      were collected before (residual) and 2 hours (T2) after drug intake. Cholesterol,
      triglycerides, alanine transaminase, aspartate transaminase, and gamma-glutamyl
      transpeptidase were assessed at the same time. The median values of ritonavir
      residual and T2 levels were 1.64 mg/L and 5.9 mg/L at observation 1 and 3.35 mg/L
      and 6.29 mg/L at observation 2, respectively. According to virologic response,
      median residual concentrations of ritonavir were 3.17, 2.52, and 1.04 mg/L for
      the complete, the partial, and the no-response groups. The authors observed a
      wide intersubject variability of ritonavir concentrations with an increase in
      residual levels between the two observation periods. Residual levels were
      correlated with virologic response whereas there was no direct association
      between T2 levels and long-term response. Patients with complete or partial
      response displayed statistically significantly higher residual concentrations
      than the no-response group. No correlation could be demonstrated between elevated
      plasma drug concentrations and abnormal cholesterol or triglycerides values.
      These results emphasize the importance of a sustained high ritonavir
      concentration to achieve optimal treatment efficacy. Furthermore, these results
      prove the clinical benefit of therapeutic drug monitoring and could potentially
      improve patient evaluation in terms of treatment efficacy, compliance, and viral
      resistance.

PMID- 10942180
TI  - Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in
      plasma, saliva, and urine.
AB  - Twenty-five healthy volunteers were given 100 mg caffeine orally and several
      estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation
      was performed by correlation of different parameters in plasma, saliva, and urine
      to two measures of caffeine clearance, CL(oral) and CL(137X-->17X) that served as
      standards of reference. Two subjects were excluded because of noncompliance with
      a caffeine-free diet. In the remaining 23 subjects, both plasma and saliva total
      clearances of caffeine were highly correlated with each other (r(s) = 0.97, p <
      0.0001). The ratio 17X/137X restricted to one sampling point taken 4 hours after
      dose, showed a high correlation (r(s)) with CL(oral) and CL(137X-->17X) in plasma
      (0.84/0.83) and saliva (0.82/0.77) (p < 0.0001 for all the correlation values)
      where 17X is 1,7-dimethylxanthine (paraxanthine) and 137X is 1,3,7
      trimethylxanthine (caffeine). Additionally, the ratio (AFMU + 1U + 1X + 17U +
      17X)/137X in a 0-24 hours urine sampling showed the highest correlation with
      CL(137X-->17X) (r(s) = 0.85, p < 0.001) where AFMU is 5-acetylamino-6-formylamino
      3-methyluracil, 1U is 1-methyluracil, 1X is 1-methylxanthine, and 17U is 1,7
      dimethyluric acid. The major estimates of CYP1A2 activity were significantly less
      in nonsmoking females, and this probably was related to the use of oral
      contraceptives in this subpopulation. In summary, among caffeine-based approaches
      for CYP1A2, the authors recommend either plasma or saliva 17X/137X ratio and the
      urinary (AFMU + 1U + 1X + 17U + 17X)/137X ratio during a sampling interval of at
      least 8 hours, starting at time zero since caffeine intake. These indices are
      simple, reliable, and relatively inexpensive estimates of CYP1A2 activity to be
      used in the study of human populations.

PMID- 10942181
TI  - Simultaneous determination of fenfluramine and phentermine in urine using gas
      chromatography mass spectrometry with pentafluoropropionic anhydride
      derivatization.
AB  - Fenfluramine and phentermine ('fen-phen') are stimulants used primarily for
      weight loss that have a causative association with serious health problems.
      Though voluntarily removed from the market by their manufacturers and the FDA in
      September of 1997, both drugs occasionally reappear in the clinical and forensic
      setting from individuals who retained old prescriptions, transported the drugs
      from foreign countries, or 'stockpiled' the medications immediately before their
      removal from the market. The authors describe an analytical method for
      simultaneous detection of fenfluramine, phentermine, and the internal standard, N
      propylamphetamine, in urine using pentafluoropropionic anhydride derivatization.
      Detection using and mass spectrometry is described. Baseline resolution of the
      analytes was achieved in the presence of four other common sympathomimetic
      amines. The increased molecular weights, better peak profiles, and characteristic
      fragments containing portions of both derivatizing agent and parent compound aid
      in the unambiguous identification of these analytes.

PMID- 10942183
TI  - Time-dependent absorption of therapeutic drugs by the gel of the Greiner Vacuette
      blood collection tube.
AB  - Stability of therapeutic drugs in sera collected in Becton-Dickinson VACUTAINER
      serum separator SST tubes has been well studied. Recently, the Greiner Vacuette
      serum separator tube has become available for blood collection. However,
      stability of therapeutic drugs in sera when the specimen is collected in the
      Greiner tube has not been reported. The authors studied the stability of 15
      commonly monitored drugs in sera when stored on the gel of the Greiner serum
      separator tubes. The drugs studied were amikacin, gentamycin, tobramycin,
      vancomycin, digoxin, quinidine, theophylline, carbamazepine, phenobarbital,
      phenytoin, valproic acid, tricyclic antidepressants, salicylate, acetaminophen,
      and ethanol. The authors compared the concentrations of drugs in sera stored in
      plain tubes (no gel) and in sera stored in the Greiner tubes containing serum
      separator gel. They observed a significant decline in the concentrations of
      tricyclic antidepressants when stored in the Greiner tubes. Interestingly,
      concentrations of amitriptyline declined more than its metabolite nortriptyline
      and concentration of imipramine also decreased more than its metabolite
      desipramine. The concentration of carbamazepine also decreased slightly over time
      when serum was stored in the Greiner tube. Although declines in carbamazepine
      concentrations on prolonged storage in the Greiner tubes were statistically
      significant, the decreases may not be clinically significant. The concentrations
      of the other drugs studied did not decline when stored in the Greiner tubes. The
      authors conclude that the Greiner brand tube is not suitable for blood collection
      for analysis of tricyclic antidepressants.

PMID- 10942182
TI  - Stability of sirolimus (rapamycin) in whole blood.
AB  - The effects of storage time (0-8 days), temperature (4 degrees C and 30 degrees C
      in dark and light), and freeze-thaw cycles on the stability of sirolimus in blood
      were examined. Sirolimus quantification was undertaken using HPLC-electrospray
      tandem mass spectrometry. Whole blood samples supplemented with sirolimus (5.0,
      15.0, and 30.0 microg/L) and pooled renal and heart transplant samples were found
      to be stable during the 8 days under all conditions (<10% decrease in
      concentration). No significant difference was observed in sirolimus concentration
      between freshly collected patient samples and sirolimus-supplemented samples
      (5.0, 15.0, and 30.0 microg/L) after three freeze-thaw cycles (p > 0.198). In
      conclusion, blood samples can be transported with or without cooling for up to 8
      days without sirolimus results being compromised. The reanalysis of sirolimus
      samples, which may entail freeze-thaw cycles, can be undertaken if the number of
      cycles is three or less.

PMID- 10942184
TI  - Correlation of serum and salivary levels of pentoxifylline.
AB  - Twelve healthy volunteers were treated with 400 mg pentoxifylline at 1000 and
      2200 hours in a randomized crossover design with a washout period of 1 week.
      Serum and saliva samples were analyzed for unchanged pentoxifylline by high
      performance liquid chromatography. Saliva to serum ratios and pharmacokinetic
      parameters of pentoxifylline were calculated. Significant (p < 0.05) correlation
      between serum and salivary levels of pentoxifylline was observed for the
      treatments at 1000 and 2200 hours. Although the mean saliva/serum ratios of
      pentoxifylline in the postabsorption phase were found to be higher for the 2200
      hour treatment than the 1000-hour treatment, this difference was not
      statistically significant (p > 0.05). Further, no significant (p > 0.05)
      difference was noted between the mean pharmacokinetic parameters of
      pentoxifylline whether computed through serum or through salivary levels for
      either treatment. Hence, saliva can be used in place of serum/plasma in
      pharmacokinetic and interaction studies of pentoxifylline.

PMID- 10942185
TI  - Saliva as a specimen for monitoring compliance but not for predicting plasma
      concentrations in patients with HIV treated with indinavir.
AB  - The presence of the HIV-protease inhibitor indinavir in saliva was analyzed to
      investigate whether salivary indinavir concentrations are applicable to monitor
      compliance and/or predict plasma indinavir levels. Fourteen HIV-infected
      outpatients treated with indinavir and 24 healthy volunteers who ingested a
      single dose of indinavir were included. Paired plasma and citric-acid-stimulated
      saliva samples were analyzed by high-performance liquid chromatography (HPLC).
      Stimulated salivary indinavir concentrations showed a high correlation (r = 0.85,
      p < 0.01) with corresponding plasma levels. The median saliva/plasma ratio was
      65% (P25 50%; P75 94%). The ratios were independent of the plasma concentration;
      however, a relation with time after ingestion was seen. The unbound fraction of
      indinavir in plasma was not significantly correlated with the saliva/plasma ratio
      after stimulated saliva collection, in contrast with a subset of nonstimulated
      saliva from healthy volunteers, where we did find a significant correlation.
      Although stimulated salivary indinavir concentrations are highly correlated with
      plasma concentrations, it is not possible to predict plasma indinavir levels by
      the salivary concentrations for purposes of therapeutic drug monitoring, due to
      large interindividual and intraindividual variation. Nevertheless, monitoring
      compliance by measuring the presence of indinavir in saliva is possible:
      ingestion of indinavir can be assessed with a sensitivity of 84.8% in the whole
      dosing interval or with 98.8% between 1 and 6 hours after the last dose, which is
      comparable with plasma.

PMID- 10942186
TI  - Therapeutic drug monitoring of sertraline: variability factors as displayed in a
      clinical setting.
AB  - This report describes sertraline pharmacokinetics derived from routine
      therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic
      method with ultraviolet detection was established for routine sertraline TDM, and
      924 analyses were performed from April 1995 to May 1997. Extensive predefined
      inclusion/exclusion criteria were applied to increase the validity of
      scientifically evaluated data. Subsequently, 605 samples (65.5%) were excluded.
      The remaining 319 samples from 319 patients, representative of steady state
      trough specimens and accompanied by essential clinical information provided on
      request forms, were scrutinized. A pronounced interindividual variability was
      observed. Smokers had significantly lower concentration-to-dose (C/D) mean ratios
      of serum sertraline (s-sert) and its main metabolite desmethylsertraline (s
      dsert) than nonsmokers. Higher s-sert and s-dsert C/D mean ratios were found in
      elderly patients than in adults aged less than 65 years. In a subset of 20
      patients in whom repeated TDM analyses were performed, observed intraindividual
      sertraline TDM outcome variability was low. The results highlight sertraline TDM
      as a tool for individual dose optimization and evaluation of patient drug
      compliance as well as drug-drug interactions.

PMID- 10942187
TI  - Histologic determinants of monoethylglycinexylidide formation in patients with
      chronic hepatitis C.
AB  - Patients affected by chronic hepatitis C (CHC) display a peculiar histologic
      picture characterized by the presence of steatosis and bile duct damage in
      addition to evidence of inflammation, necrosis, and fibrosis. In the staging of
      these patients, functional evaluation may be considered a complementary tool. The
      monoethylglycinexylidide (MEGX) test has been used in diagnostic and prognostic
      assessment of chronic liver disease as a quantitative liver function test. In
      this study the authors evaluated whether different sampling times for the test
      could reflect different histologic patterns. The authors studied 82 patients with
      biopsy-proven CHC who underwent functional evaluation by means of MEGX test. The
      authors found that MEGX15 better reflected the histologic findings of necrosis
      and inflammation, and MEGX60 the presence of fibrosis. Neither steatosis nor bile
      duct damage showed a strong correlation with either sampling time. Moreover, MEGX
      levels showed a progressive decrease as histologic grading of chronic hepatitis
      progressively increased. Stepwise regression analysis identified necrosis and
      inflammation as histologic variables associated with both MEGX15 and MEGX30, and
      fibrosis as a variable associated with MEGX60. These results suggest that a
      decline in liver metabolic function corresponds to a progressive increase in
      liver damage, and that this circumstance should be taken into account when
      prescribing drugs to patients with CHC.

PMID- 10942188
TI  - Comparison of topiramate concentrations in plasma and serum by fluorescence
      polarization immunoassay.
AB  - Topiramate has been recently licensed as an antiepileptic drug. A fluorescence
      polarization immunoassay (FPIA), the Innofluor, has been developed to determine
      topiramate in heparinized plasma. Since therapeutic drug monitoring laboratories
      may not have control over collection of the samples submitted to them, it is
      important for analytical methods to be robust and able to cope with any specimen.
      The effect of different anticoagulants on the topiramate FPIA assay was
      investigated by collecting blood from 50 patients with epilepsy being maintained
      on a range of topiramate doses as part of their therapy. After venesection the
      blood was divided among four tubes: plain, heparinized, EDTA, and
      fluoride/oxalate. Erythrocytes were separated by centrifugation and supernatant
      fluid frozen to await duplicate assay by FPIA. Results were compared by means of
      Altman and Bland difference plots which indicated that there was no significant
      difference between values obtained with heparinized plasma and the other fluids.
      It was concluded that the Innofluor assay is robust and gives similar results
      when blood samples are collected into any of the specified anticoagulants.

PMID- 10942189
TI  - Simultaneous determination of the five HIV-protease inhibitors: amprenavir,
      indinavir, nelfinavir, ritonavir, and saquinavir in human plasma by solid-phase
      extraction and column liquid chromatography.
AB  - A sensitive and selective liquid chromatographic assay has been developed for the
      determination of the five protease inhibitors currently approved by the Food and
      Drug Administration (FDA) (amprenavir, indinavir, nelfinavir, ritonavir, and
      saquinavir) in a single run. Pretreatment of a 1-mL plasma sample spiked with
      internal standard was made by a solid-phase extraction procedure using a
      polymeric reversed-phase sorbent. Liquid chromatography was performed using a
      narrowbore C18 reversed-phase column and gradient elution. A double ultraviolet
      detection at 265 nm (amprenavir) and at 210 nm (indinavir, nelfinavir, ritonavir,
      saquinavir and internal standard) was used. Calibration curves were linear in the
      range 25-10000 ng/mL and the assay has been validated over the range 25-5000
      ng/mL. Average accuracy at four concentrations was in the range of 100.5-104.2%
      and 96.9-100.5% for within-day and between-day, respectively. The coefficients of
      variation were less than 10%. Mean absolute recoveries varied from 85.4%
      (ritonavir) to 98.8% (saquinavir). No metabolite of the protease inhibitors was
      found to coelute with the drugs of interest or with the internal standard. At
      this time, among the tested drugs, especially all the presently licensed
      nucleoside and nonnucleoside reverse transcriptase inhibitors that can be used in
      combination with the protease inhibitors, none was found to interfere with the
      assay. This method is now in use in the authors' laboratory for the therapeutic
      monitoring of the HIV-protease inhibitors.

PMID- 10942190
TI  - Evaluation of the AxSYM monoclonal cyclosporin assay and comparison with
      radioimmunoassay.
AB  - Recently, a semiautomated fluorescence polarization immunoassay (FPIA) for
      determination of parent cyclosporin (CsA) has been developed for the Abbott AxSYM
      system. The new CsA assay measures the drug from an extracted whole blood
      specimen. The authors report here the evaluation of this new assay and the
      comparison with a previously validated radioimmunoassay (RIA) method (CYCLO-Trac
      SP). To assess the imprecision, the authors used tri-level controls supplied by
      both Abbott and Bio-Rad manufacturers. The within-run CV ranged from 4.4% to 7.3%
      and the between-day CV ranged from 4.4% to 7.6%. Mean recovery of the drug from
      clinical specimens spiked with kit calibrators was 108.4%. Fluorescence
      polarization immunoassay AxSYM (y) was correlated to RIA (x) by using 132 trough
      blood specimens (44 renal, 44 liver, and 44 heart) from transplant recipients and
      resulted in the following Passing-Bablok linear regression equation: y = 6.7 +
      0.97x, r = 0.989, S(x/y) = 12.9. The percentage of overestimation (mean, range)
      by FPIA AxSYM versus RIA was (3.8%, range -17.7% to 39.1%). The results observed
      with this new method from follow-up studies in patients during the early course
      after transplant were not consistently higher than those obtained by RIA. These
      findings contrast with previously reported results that compared FPIA TDx assay
      with RIA. The authors conclude that FPIA AxSYM is a precise method for measuring
      CsA and offers results similar to those obtained by RIA with a marked reduction
      in assay time.

PMID- 10942191
TI  - Plasma concentrations of risperidone and 9-hydroxyrisperidone: effect of
      comedication with carbamazepine or valproate.
AB  - To evaluate the pharmacokinetic interaction between risperidone and the mood
      stabilizing agents carbamazepine and valproic acid, steady state plasma
      concentrations of risperidone and 9-hydroxyrisperidone (9-OH-risperidone) were
      compared in patients treated with risperidone alone (controls, n = 23) and in
      patients comedicated with carbamazepine (n = 11) or sodium valproate (n = 10).
      The three groups were matched for sex, age, body weight, and antipsychotic
      dosage. Plasma concentrations of risperidone and 9-OH-risperidone did not differ
      between valproate-comedicated patients and controls. By contrast, the
      concentrations of both compounds were lower in patients taking carbamazepine,
      although the difference reached statistical significance only for the metabolite
      (p < 0.001). The sum of the concentrations of risperidone and 9-OH-risperidone in
      patients receiving carbamazepine (median 44 nmol/L) was also significantly lower
      than in patients receiving valproate (168 nmol/L) and in controls (150 nmol/L).
      In five patients assessed with and without carbamazepine comedication, dose
      normalized plasma risperidone and 9-OH-risperidone concentrations were
      significantly lower when the patients received combination therapy than when they
      received risperidone alone. In three patients assessed with and without
      valproate, no major changes in the levels of risperidone and its metabolite were
      observed. These findings demonstrate that carbamazepine markedly decreases the
      plasma concentrations of risperidone and its active 9-OH-metabolite, probably by
      inducing CYP3A4-mediated metabolism. This interaction is likely to be clinically
      significant. Conversely, valproic acid does not cause any major change in plasma
      antipsychotic levels.

PMID- 10942192
TI  - Evaluation of analytical and clinical performance of a dual-probe phenotyping
      method for CYP2D6 polymorphism and CYP3A4 activity screening.
AB  - A bioanalytical method for the determination of dextromethorphan (DEX) and its
      metabolites dextrorphan (DTX), 3-methoxymorphinan (3MM), and 3-hydroxymorphinan
      (3HM) in human urine was developed for CYP2D6 phenotyping and CYP3A4 activity
      measurements in clinical pharmacology studies using dextromethorphan administered
      in a drinking solution as substrate. The method was evaluated by thorough
      conventional validation and by a cross-validation of the method with a previously
      applied method for dextromethorphan and dextrorphan only (CYP2D6 phenotyping).
      Cross-validation with the former method showed no significant differences in
      measured concentrations of volunteer samples. This guaranteed the consistency of
      epidemiologic data in the database collected from two methods. For the CYP2D6 and
      CYP3A4 evaluations, the clinical parameters are ratios of concentrations. It
      appeared that severe variance in individual concentrations generally did not
      influence the variance of ratios significantly, because experimental errors in
      concentrations of two analytes proved to correlate considerably. For CYP2D6
      values around the antimodes, the chance of a misclassification is very small. The
      chance of classifying an extensive metabolizer as a poor metabolizer or vice
      versa is negligible. For CYP3A4 activity determinations it was concluded that in
      general a change in dextromethorphan/3-methoxymorphinan (DEX/3MM) ratios of 10%
      or more as detected with the current method, is a significant increase or
      decrease in the activity of CYP3A4. The authors concluded that they had obtained
      an analytically valid and clinically reliable bioanalytical method for the
      determination of dextromethorphan and its metabolites dextrorphan, 3
      methoxymorphinan, and 3-hydroxymorphinan in human urine for CYP2D6 phenotyping
      and CYP3A4 activity measurements for clinical pharmacology studies.

PMID- 10942193
TI  - Extract versus herb: effect of formulation on the absorption rate of botanical
      ephedrine from dietary supplements containing Ephedra (ma huang).

PMID- 10942194
TI  - Response to letter from van Gelder. Drug interaction between mycophenolate
      mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring
      in renal transplant patients.

PMID- 10942195
TI  - Ligation of Fc receptor of macrophages stimulates protein kinase C and anti
      leishmanial activity.
AB  - Fc receptors are known to express on the surface of mature monocytes, macrophages
      and lymphocytes. In this study a ligand e.g. liposomal IgG (human IgG coupled to
      PE-liposome via carbodimide reaction) was developed to ligate the Fc receptor of
      macrophages. When liposomal IgG was incubated with macrophages at 37 degrees C
      for 5 min, it induced the macrophage activation which suppress the parasite
      burden approximately to an extent of 60%, 50% and 45%, when macrophages were
      infected with UR6, AG83 and GE1 strains of L-donovani respectively. Superior
      efficacy of liposomal IgG were achieved compared to the treatment with free IgG
      and free liposomes. The activity of protein kinase C (PKC) has been found to be
      higher in the Fc receptor targeted macrophage membrane fraction, suggesting its
      translocation from the cytosol. Staurosporine, a potent inhibitor of the enzyme
      protein kinase C (PKC) has been found to protect the parasite inside the
      macrophage indicating the role of PKC in the signaling process. The liposomal IgG
      treatment has been found to induce the generation of significant amount of
      superoxide and hydrogen peroxide which helped to suppress the parasite burden.
      Further when liposomal IgG were incubated with IFN-gamma primed, LPS activated
      macrophages, a significant amount of NO release was also noticed, indicating its
      role in parasite killing. The above results suggest that Fc receptor mediated
      activation by liposomal IgG may be used as an alternative approach to kill
      parasites intracellularly.

PMID- 10942196
TI  - Characterization of fibroblast cytoplasmic proteins that bind to the 3' UTR of
      human catalase mRNA.
AB  - The excessive expression of catalase protein and its activity in cultured skin
      fibroblast from Zellweger Syndrome (ZS), a disorder of peroxisomal biogenesis,
      was found to be regulated at the translational level (J. Neurochem. 67: 2373
      2378, 1996). Overall there is a considerable increase in the association of
      catalase mRNA with polysomes in ZS cell lines as compared to control indicating
      translational upregulation. To investigate the possibility that RNA-protein
      interactions are involved in the mediation of this increase in translation, the
      interaction between 3' untranslated region of human catalase mRNA and human
      fibroblast cytoplasmic proteins were investigated by RNA gel shift assay
      technique. Competition experiments demonstrated that all the 600 bases of 3' UTR
      (of human catalase gene) was required for efficient binding. Catalase RNA-
      protein interaction was sensitive to the altered redox state in these in vitro
      assays and this RNA-protein interaction could be enhanced by the addition of beta
      mercaptoethanol in cytoplasm from control fibroblast but not in cytoplasm from ZS
      fibroblast. UV cross linked RNA-protein complexes on SDS polyacrylamide gel
      electrophoresis revealed the presence of at least four protein bands with
      approximate molecular masses of 38 kDa, 50 kDa, 66 kDa and 80 kDa. The potential
      role of these mRNA binding proteins in the regulation of catalase gene expression
      is discussed.

PMID- 10942197
TI  - Upstream regulatory elements in chick heme oxygenase-1 promoter: a study in
      primary cultures of chick embryo liver cells.
AB  - Previously, chick heme oxygenase-1 (cHO-1) gene was cloned by us and two regions
      important for induction by sodium arsenite were identified. These two regions
      were found to contain consensus sequences of an AP-1 (-1580 to -1573) and a
      MRE/cMyc complex (-52 to -41). In the current study, the roles of these two
      elements in mediating the sodium arsenite or cobalt chloride dependent induction
      of cHO-1 were investigated further. DNA binding studies and site-directed
      mutagenesis studies indicated that both the AP-1 and MRE/cMyc elements are
      important for the sodium arsenite induction, while cobalt chloride induction
      involves only the AP-1 element. Electrophoretic mobility shift assays showed that
      nuclear protein binding to the AP-1 element was increased by both sodium arsenite
      or cobalt chloride treatment, whereas the binding of proteins to the MRE/cMyc
      element showed a high basal expression in untreated cells and the binding
      activity was only slightly increased by sodium arsenite treatment. Site-directed
      mutagenesis studies showed that, to completely abolish sodium arsenite induction,
      both the AP-1 and MRE/cMyc elements must be mutated; mutation of either element
      alone resulted in only a partial effect. In contrast, a single mutation at AP-1
      element was sufficient to reduce the cobalt chloride induction almost completely.
      The MRE/cMyc complex plays a major role in the basal level expression, and shares
      some similarities to the upstream stimulatory factor element (USF) identified in
      the promoter regions of mammalian HO-1 genes and other stress regulated genes.
      Because sodium arsenite is known to cause oxidative stress and because activation
      of AP-1 proteins has been shown to be a key step in the oxidative stress response
      pathway, we also explored the possibility that the induction of the cHO-1 gene by
      sodium arsenite is mediated through oxidative stress pathway(s) by activation of
      AP-1 proteins. We found that pretreatment with antioxidants (N-acetyl cysteine or
      quercetin) reduced the induction of the endogenous cHO-1 message or cHO-1
      reporter construct activities induced by sodium arsenite or cobalt chloride.
      These antioxidants also reduced the protein binding activities to the AP-1
      element in the electrophoretic mobility shift assays. In summary, induction of
      the cHO-1 gene by sodium arsenite or cobalt chloride is mediated by activation of
      the AP-1 element located at -1,573 to -1,580 of the 5'UTR.

PMID- 10942198
TI  - Activation of mitogen-activated protein kinases during natural freezing and
      thawing in the wood frog.
AB  - The responses of mitogen-activated protein kinase (MAPK) family members,
      including ERK (extracellular signal-regulated kinase), JNK (c-Jun NH2-terminal
      kinase), and p38, in the metabolic responses to whole animal freezing (up to 24 h
      frozen at -2.5 degrees C) and thawing (up to 4 h at 5 degrees C after a 12 h
      freeze) were examined in four organs (liver, kidney, heart, brain) of the freeze
      tolerant wood frog Rana sylvatica. Levels of the active phosphorylated form of
      p38 increased within 20 min as an early response to freezing in liver and kidney
      but rose later (after 12 h) in heart. Both JNK and p38 were activated during
      thawing in liver, kidney and heart with temporally-distinct patterns in each
      organ. The only MAPK response to freeze/thaw in frog brain was a transient
      elevation of p38 after 90 min thawing. ERK activity did not respond to
      freeze/thaw in any organ. The levels of c-Fos increased during freezing in kidney
      and brain whereas c-Jun was unaffected by freeze/thaw. Organ-specific responses
      by MAPKs, particularly p38, suggest that these may have roles in regulating
      metabolic or gene expression responses that may be adaptive in dealing with
      freezing stress or metabolic recovery during thawing.

PMID- 10942200
TI  - Vanillin as an antioxidant in rat liver mitochondria: inhibition of protein
      oxidation and lipid peroxidation induced by photosensitization.
AB  - Using rat liver mitochondria, as model systems, we have examined the ability of
      the natural compound and the food-flavoring agent, vanillin to protect membranes
      against oxidative damage induced by photosensitization at concentrations normally
      used in food preparations. Vanillin, at a concentration of 2.5 mmol/L, has
      afforded significant protection against protein oxidation and lipid peroxidation
      in hepatic mitochondria induced by photosensitization with methylene blue plus
      light. The effect observed was both time- and concentration-dependent. The
      inhibitory effect is similar to ascorbic acid and the singlet oxygen quencher,
      diazabicyclo[2.2.2]octane (DABCO) but less effective than sodium azide and
      glutathione. Examination of possible mechanisms responsible for the observed
      protection, showed that vanillin has a significant ability to quench singlet
      oxygen (1O2), a reactive species responsible for damage induced during
      photosensitization by Type II mechanism. Hence, this flavoring compound, due to
      its antioxidant ability, may have potential to prevent oxidative damage to
      membranes in mammalian tissues and thereby the ensuing diseased states.

PMID- 10942199
TI  - MET-88, a gamma-butyrobetaine hydroxylase inhibitor, improves cardiac SR Ca2+
      uptake activity in rats with congestive heart failure following myocardial
      infarction.
AB  - We previously reported that MET-88, 3-(2,2,2-trimethylhydrazinium) propionate,
      improved left ventricular diastolic dysfunction induced by congestive heart
      failure (CHF) in rats. The present study was designed to investigate the
      mechanism by which MET-88 improved the cardiac relaxation impaired in CHF rats.
      The left coronary artery of the animals was ligated, and the rats were then
      orally administered vehicle (control), MET-88 at 50 or 100 mg/kg or captopril at
      20 mg/kg for 20 days. Myocytes were isolated from the non-infarcted region in the
      left ventricle, and cell shortening and [Ca2+]i transients were measured with a
      video-edge detector and by fluorescence analysis, respectively. In CHF control
      rats, the diastolic phase of cell shortening was prolonged compared with that of
      the sham-operated (sham) rats. This prolongation was prevented by treatment with
      MET-88 at 100 mg/kg or captopril at 20 mg/kg. CHF control rats also showed an
      increase in the decay time of [Ca2+]i transients compared with sham rats. MET-88
      at 100 mg/kg and captopril at 20 mg/kg attenuated the increase in decay time of
      [Ca2+]i transients. Ca2+ uptake activity of the sarcoplasmic reticulum (SR)
      isolated from the non-infarcted region in the left ventricle was measured, and
      Lineweaver-Burk plot analysis of the activity was performed. CHF control rats
      revealed a decrease in the Vmax for SR Ca2+ uptake activity without alteration in
      Kd. MET-88 at 100 mg/kg significantly prevented the decrease in Vmax, but had no
      effect on Kd. Also, treatment with MET-88 at 100 mg/kg improved myocardial high
      energy phosphate levels impaired in CHF rats. These results suggest that one of
      the mechanisms by which MET-88 improved cardiac relaxation in CHF rats is based
      on the amelioration of [Ca2+]i transients through increase of SR Ca2+ uptake
      activity.

PMID- 10942201
TI  - Cerebral antioxidant status and free radical generation following glutathione
      depletion and subsequent recovery.
AB  - This study was aimed to evaluate the oxidative damage, production of reactive
      oxygen species and the status of antioxidative defenses following cerebral GSH
      depletion induced by two classical depletors, diethylmaleate (DEM, 3 mmol/kg,
      i.p.) and phorone (PHO, 4 mmol/kg, i.p.). The treatment decreased (40-43%) brain
      glutathione levels at 2 h, followed by a partial recovery at 24 h. Cerebral
      glutathione depletion by these agents increased the levels of superoxide anion
      and hydroxyl radical at both the time intervals; however, hydrogen peroxide was
      high at 24 h only. It also produced a dramatic increase in the protein carbonyls
      at 2 h but not at 24h, without any significant effect on lipid peroxidation and
      conjugated diene levels. These rats showed a significantly lowered superoxide
      dismutase activity both at 2 h and 24 h of exposure, as compared to controls.
      Glutathione depletion enhanced catalase activity markedly at 2 h, followed by
      some recovery at 24 h. While Se-independent glutathione peroxidase (GPx) and
      glutathione S-transferase activities were increased at both 2 and 24 h time
      intervals, Se-dependent GPx and glucose-6-phosphate dehydrogenase were induced at
      2 h only. Glutathione depletion decreased ceruloplasmin and vitamin E levels
      significantly at 2 h. However, ascorbic acid remained unaffected. It may be
      concluded that an acute cerebral glutathione depletion generates higher levels of
      reactive oxygen species, which may be responsible for oxidative modification of
      proteins. Some of these changes appear to recover soon after an activation of a
      variety of cellular antioxidant defense mechanisms and glutathione restoration.
      It appears that central nervous system is highly vulnerable to oxidative damage
      following a moderate glutathione depletion that may result from certain diseases
      or xenobiotic exposures.

PMID- 10942202
TI  - Sequestered actin in chick embryo fibroblasts.
AB  - Chick embryo fibroblasts contain about 75-100 microM unpolymerized actin and at
      least four proteins which can bind actin monomers, actin depolymerizing factor
      (ADF), gelsolin, profilin, and thymosin beta4 (Tbeta4). Fibroblast extracts are
      analyzed by non-denaturing polyacrylamide gel electrophoresis and immunoblotting
      where most of the G-actin is detected as a complex with Tbeta4. When fibroblast
      extracts are fractionated by gel filtration and the fractions are analyzed by
      PAGE and HPLC, most of the G-actin elutes in a peak that also contains Tbeta4 at
      an overall molar ratio of 1.9:1 relative to actin. Gelsolin, profilin, and ADF
      are also detectable in the gel filtration eluate and at least partly coelute with
      actin, and account for only a minor fraction of the soluble actin pool. These
      observations indicate that under the growth conditions studied, Tbeta4 is the
      major actin-sequestering protein in fibroblasts.

PMID- 10942203
TI  - Protein kinase C-gamma phorbol-binding domain involved in protein-protein
      interaction.
AB  - Protein kinase C-gamma (PKC-gamma) contains two cysteine-rich regions (Cys1,
      Cys2) responsible for interaction with phospholipids. However, previous
      experiments suggested that, only Cys1 represents the high affinity site involved
      in diacylglycerol-dependent activation of PKC-gamma. This raises the question
      whether Cys2 might participate in other functions of the PKC-gamma regulatory
      domain. The purpose of our studies was to examine the ability of Cys2 domain to
      bind cellular proteins. The Cys2 domain (residues 92-173) was expressed as a
      fusion protein with glutathione-S-transferase (GST) in Escherichia coli and
      purified. In order to investigate protein-protein interaction of Cys2 domain we
      used affinity column and an overlay assay. Our results demonstrate that the Cys2
      domain of PKC-gamma binds several proteins from rat brain extracts. In the
      absence of phospholipids the Cys2 domain binds some proteins in the cytosolic
      fraction of rat brain, but no binding was detected with the proteins extracted
      from particulate fraction. Ca2+ at 1 microM concentration potentiated binding of
      cellular proteins to Cys2 domain. In the absence of Ca2+ the Cys2 domain binds
      proteins in the cytosolic fraction of rat brain in the presence of
      phosphatidylserine and to the lesser extend in the presence of
      phosphatidylinositol but neither phosphatidylcholine nor
      phosphatidylethanolamine. These results suggest that the Cys2 domain of PKC-gamma
      has the ability to interact with two classes of proteins. One class binds the
      Cys2 domain in the phosphatidylserine dependent fashion, and the other proteins
      bind Cys-2 domain in the Ca2+ dependent and phospholipid independent manner.

PMID- 10942205
TI  - Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of
      secoisolariciresinol diglucoside (SDG).
AB  - Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant
      activity and has been shown to prevent hypercholesterolemic atherosclerosis. An
      investigation was made of the effects of SDG on the development of diabetes in
      diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes
      [insulin dependent diabetes mellitus (IDDM)] to determine if this type of
      diabetes is due to oxidative stress and if SDG can prevent the incidence of
      diabetes. The rats were divided into three groups: Group I, BioBreeding normal
      rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp
      treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was
      determined by measuring lipid peroxidation product malondialdehyde (MDA) an index
      of level of reactive oxygen species in blood and pancreas; and pancreatic
      chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of
      diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by
      glycosuria and hyperglycemia. SDG prevented the development of diabetes by
      approximately 71%. Development of diabetes was associated with an increase in
      serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in
      development of diabetes by SDG was associated with a decrease in serum and
      pancreatic-MDA and an increase in antioxidant reserve. These results suggest that
      IDDM is mediated through oxidative stress and that SDG prevents the development
      of diabetes.

PMID- 10942204
TI  - Toxoplasma gondii induces the secretion of monocyte chemotactic protein-1 in
      human fibroblasts, in vitro.
AB  - Secretion of Monocyte Chemotactic Protein-1 (MCP-1) by fibroblasts infected with
      Toxoplasma gondii was studied in vitro. A significantly higher MCP-1 secretion
      was observed 24 h after infection by live tachyzoites. Analysis of chemokine mRNA
      transcripts by RNase protection assay revealed that this MCP-1 secretion seems
      associated with increased MCP-1 mRNA expression. However, these increased levels
      of MCP-1 secretion and expression were not obtained after stimulation by heat
      killed tachyzoites or parasites pre-treated by a specific inhibitor of
      phosphatidylcholine-specific phospholipase C (D609). Inhibition of parasite
      multiplication by pyrimethamine did not modify MCP-1 secretion. Thus, it appeared
      that the active penetration of T. gondii in cells was of major importance in the
      induction of MCP-1 secretion. None of the other chemokines studied by RNase
      protection assay (lymphotactin, RANTES, IP-10, MIP-1alpha, MIP-1beta, IL-8, and I
      309) were expressed after infection by live tachyzoites. We also found that MCP-1
      secretion induced by live T. gondii is blocked by inhibitors of nuclear factor
      (NF)-kappaB activation, ALLN and MG132. Such data indicate that NF-kappaB could
      be involved in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute
      to the recruitment of monocytes and lymphocytes and thus participate in the
      control of T. gondii infection and in its pathogenesis.

PMID- 10942206
TI  - Dietary alterations in protein, carbohydrates and fat increase liver protein
      turnover rate and decrease overall growth rate in the rainbow trout (Oncorhynchus
      mykiss).
AB  - We have determined the protein-turnover rates and nucleic-acid concentrations in
      the liver of trout (Oncorhynchus mykiss) fed on two different isocaloric diets:
      low-protein/high-fat and non-carbohydrate/high-fat. Compared to controls, the
      partial replacement of protein with fat significantly decreased the protein
      accumulation rate and protein-retention efficiency in the liver whilst increasing
      the fractional protein-synthesis and protein-degradation rates as well as protein
      synthesis efficiency. The complete replacement of carbohydrates with fat
      significantly lowered the protein-accumulation rate and protein-retention
      efficiency, but enhanced both the protein-synthesis and protein-degradation rates
      as well as protein-synthesis capacity. The protein:DNA and RNA:DNA ratios
      decreased considerably on both diets. Total DNA decreased in fish on a low
      protein/high-fat diet but did not change in those on a non-carbohydrate/high-fat
      diet. The absolute protein-synthesis rate registered no significant change under
      any of the nutritional conditions. Both the experimental diets did however raise
      the fractional protein-synthesis rate significantly, due to enhanced protein
      synthesis efficiency when protein was partially replaced with fat and to enhanced
      protein-synthesis capacity when carbohydrates were completely replaced with fat.
      Our results show the capacity of the liver to adapt its turnover rates and
      conform to different nutritional conditions. They also point to the possibility
      of controlling fish growth by dietary means.

PMID- 10942207
TI  - Thermal analysis of the plasma membrane Ca2+-ATPase.
AB  - The plasma membrane Ca2+-ATPase is a well known enzyme in eucaryotes able to
      extrude calcium to the extracellular space in order to restore intracellular
      calcium to very low levels. This ATPase needs plasma membrane lipids such as
      acidic phospholipids in order to maintain its activity. In this study, we
      investigated the role that calcium and cholesterol play on the thermal stability
      of the Ca2+-ATPase isolated from cardiac sarcolemma and erythrocyte membranes.
      Calcium showed a stabilizing and protective effect when the enzyme was exposed to
      high temperatures. This stabilizing effect showed by calcium was potentiated in
      the presence of cholesterol. These protection effects were reflected on several
      thermodynamic parameters such as T50, deltaHvh and apparent deltaG, indicating
      that calcium might induce a conformational change stabilized in the presence of
      cholesterol that confers enzyme thermostability. The effect shown by cholesterol
      on deltaHvh and apparent deltaH++ open the possibility that this lipid decreases
      cooperativity during the induced transition. Despite that a binding site for
      cholesterol has not been identified in the plasma membrane Ca2+-ATPase, our
      results supports the proposal that this lipid interacts with the enzyme in a
      direct fashion.

PMID- 10942208
TI  - Activation of NFkappaB is necessary for IL-1beta-induced cyclooxygenase-2 (COX-2)
      expression in human gingival fibroblasts.
AB  - The immediate-early cyclooxygenase-2 (COX-2) gene encodes an inducible
      prostaglandin synthase enzyme which is implicated in inflammatory and
      proliferative diseases. COX-2 is highly induced during cell activation by various
      factors, including mitogens, hormones and cytokines. Since pro-inflammatory
      cytokine IL-1beta has been shown to induce prostaglandin E2 (PGE2) release in
      human gingival fibroblasts (HGF), here we analyzed the effect of IL-1beta on the
      expression of COX-2 and the activation of NFkappaB in HGF. Northern hybridization
      analysis revealed that IL-1beta (200 pg/ml) increased the expression of COX-2
      mRNA in HGF. The effect of IL-1beta was abrogated by herbimycin A, a protein
      tyrosine kinase inhibitor, and enhanced by orthovanadate, a protein tyrosine
      phosphatase inhibitor. IL-1beta-induced PGE2 release was blocked by the tyrosine
      kinase inhibitor and increased by the tyrosine phosphatase inhibitor. The results
      of transient transfection assays using chimeric constructs of the human COX-2
      promoter (nt -1432 approximately +59) ligated to a luciferase reporter gene
      indicated that IL-1beta stimulated the transcriptional activity approximately 1.5
      fold. Gel mobility shift assays with a radiolabelled COX-2-NFkappaB
      oligonucleotide (nts-223 to-214) revealed an increase in the binding of nuclear
      proteins from IL-1beta-stimulated HGF. This increase of DNA-protein complex
      formation induced by IL-1beta was blocked by herbimycin A and another tyrosine
      kinase inhibitor, genistein. These results suggest that NFkappaB is an important
      transcription factor for IL-1beta-induced COX-2 gene expression, and is involved
      in inducing COX-2 gene transcription through tyrosine phosphorylation in HGF.

PMID- 10942209
TI  - Copper sensitizes the mitochondrial permeability transition to
      carboxytractyloside and oleate.
AB  - Addition of 5 microM copper to rat kidney mitochondria enhances the effect of
      carboxyatractyloside and oleate on pore opening, in a cyclosporin A-sensitive
      fashion. The effects of the pair copper-carboxyatractyloside were observed on
      matrix Ca2+ efflux, mitochondrial swelling and on the transmembrane electric
      gradient. The effect of Cu2+ emphasizes the importance of membrane thiol groups
      located, probably, in the ADP/ATP translocase (ANT), on permeability transition.
      It was also found that Cu2+ does not block the fluorescent label of ANT by eosin
      5-maleimide, but abolishes the inhibition by CAT on the labeling. This suggests
      that the binding of Cu2+ to cysteine residues of ANT promotes a conformational
      change in the carrier, strengthening the effect of CAT and oleate on membrane
      leakage.

PMID- 10942210
TI  - Apolipoprotein E gene expression is reduced in apolipoprotein A-I transgenic
      mice.
AB  - The levels of plasma apolipoprotein (apo) E, an anti-atherogenic protein involved
      in mammalian cholesterol transport, were found to be 2-3 fold lower in mice over
      expressing human apoA-I gene. ApoE is mainly associated with VLDL and HDL-size
      particles, but in mice the majority of the apoE is associated with the HDL
      particles. Over-expression of the human apoA-I in mice increases the levels of
      human apoA-I-rich HDL particles by displacing mouse apoA-I from HDL. This results
      in lowering of plasma levels of mouse apoA-I. Since plasma levels of apoE also
      decreased in the apoA-I transgenic mice, the mechanism of apoE lowering was
      investigated. Although plasma levels of apoE decreased by 2-3 fold, apoB levels
      remained unchanged. As expected, the plasma levels of human apoA-I were almost 5
      fold higher in the apoAI-Tg mice compared to mouse apoA-I in WT mice. If the over
      expression of human apoA-I caused displacement of apoE from the HDL, the levels
      of hepatic apoE mRNA should remain the same in WT and the apoAI-Tg mice. However,
      the measurements of apoE mRNA in the liver showed 3-fold decreases of apoE mRNA
      in apoAI-Tg mice as compared to WT mice, suggesting that the decreased apoE mRNA
      expression, but not the displacement of the apoE from HDL, resulted in the
      lowering of plasma apoE in apoAI-Tg mice. As expected, the levels of hepatic apoA
      I mRNA (transgene) were 5-fold higher in the apoAI-Tg mice. ApoE synthesis
      measured in hepatocytes also showed lower synthesis of apoE in the apoAI-Tg mice.
      These studies suggest that the integration of human apoA-I transgene in mouse
      genome occurred at a site that affected apoE gene expression. Identification of
      this locus may provide further understanding of the apoE gene expression.

PMID- 10942212
TI  - Dehydroascorbic acid irreversibly inhibits hexokinase activity.
AB  - The oxidized form of vitamin C (dehydroascorbic acid, DHA) completely and
      irreversibly inactivates recombinant human hexokinase type I, in a pseudo-first
      order fashion. The inactivation reaction occurs without saturation, indicating
      that DHA does not form a reversible complex with hexokinase. Further
      characterization of this response revealed that the inactivation does not require
      oxygen and that dithiothreitol, while able to prevent the DHA-mediated loss of
      enzyme activity, failed to restore the activity of the DHA-inhibited enzyme.
      Inactivation was not associated with cleavage of the peptide chain or cross
      linking. The decay in enzymatic activity was however both dependent on
      deprotonation of a residue with an alkaline pKa and associated with covalent
      binding of DHA to the protein. In addition, inactivation of hexokinase decreased
      or increased, respectively, in the presence of the substrates glucose or MgATP.
      Finally, amino acid analysis of the DHA-modified hexokinase revealed a decrease
      of cysteine residues. Taken together, the above results are consistent with the
      possibility that covalent binding of the reagent with a thiol group of cysteine
      is a critical event for the DHA-mediated loss of hexokinase activity.

PMID- 10942211
TI  - High density lipoprotein, apolipoprotein A-I, and coronary artery disease.
AB  - High density lipoproteins (HDL), one of the main lipoprotein particles
      circulating in plasma, is involved in the reverse cholesterol transport. Several
      lines of evidence suggest that elevated levels of HDL is protective against
      coronary heart disease. The role of HDL in the removal of body cholesterol and in
      the regression of atherosclerosis add to the importance of understanding the
      molecular-cellular processes that determine plasma levels of HDL. Factors
      modulating plasma levels of HDL may have influence on the predisposition of an
      individual to premature coronary artery disease. Apolipoprotein (apo) A-I is the
      main apolipoprotein component of HDL and, to a large extent, sets the plasma
      levels of HDL. Thus, understanding the regulation of apoA-I gene expression may
      provide clues to raise plasma levels of HDL. This review discusses the various
      pathways that alter plasma levels of HDL. Since apoA-I is the main protein
      component of HDL and determines the plasma levels of HDL, this review also covers
      the regulation of apoA-I gene expression.

PMID- 10942214
TI  - Dexamethasone induced cardiac hypertrophy in newborn rats is accompanied by
      changes in myosin heavy chain phenotype and gene transcription.
AB  - Cardiac hypertrophy has been observed in newborn infants treated with
      dexamethasone (DEX). This study was undertaken to examine whether DEX-induced
      hypertrophy in newborn rats is associated with redistribution of cardiac myosin
      heavy chain (MHC) isoforms and, if so, the effects involve transcriptional
      regulation. Newborn rats were injected with either DEX (1 mg/kg/day; s.c.) or
      equivalent volume normal saline for 1, 3, 5, 7 or 9 days. Hypertrophy was
      quantified by heart dry/wet wt ratios, heart/body wt ratios, and total protein
      content of the myocardium. Changes in the expression of cardiac MHC mRNA were
      characterized by northern blot and slot blot analyses, using isoform specific
      probes for alpha- and beta-MHC genes. DEX effect on alpha-MHC gene transcription
      was analyzed by transiently transfecting various alpha-MHC promoter/CAT reporter
      constructs into primary cultures of cardiac myocytes derived from one day old rat
      pups. DEX administration into newborn rats produced significant cardiac
      hypertrophy ranging from 23% at day 1 to 59% at 9 days. The hypertrophy was
      accompanied by immediate increase (83%) in steady state level of the alpha-MHC
      mRNA within one day and a maximum increase (148%) at 7 days of treatment. The
      steady state level of beta-MHC mRNA declined by 25% at day 1 and a maximum
      decrease of 54% at day 7 of DEX treatment. The changes in MHC mRNA were also
      reflected in their protein levels as determined by V1 and V3 isozyme analysis.
      DEX treatment of primary cultures of cardiomyocytes following transfection with
      alpha-MHC promoter/CAT reporter constructs resulted in increased CAT expression
      in a dose dependent manner. The minimum alpha-MHC gene sequences responding to
      DEX treatment were located between the -200 to -74-bp region of the gene,
      resulting in 2-fold and 6-fold activation of CAT reporter after 0.05 and 0.1 mM
      doses of DEX, respectively. Our data indicate that DEX induced cardiac
      hypertrophy in newborn rats is accompanied by increased expression of alpha-MHC
      and decreased expression of beta-MHC. The alpha-MHC effects are mediated in part
      through transcriptional mechanisms.

PMID- 10942215
TI  - Idiopathic immune thrombocytopenic purpura: an update.

PMID- 10942216
TI  - The use of electron microscopy in the investigation of the ultrastructural
      morphology of immune thrombocytopenic purpura platelets.
AB  - Ultrastructural studies have proven useful for the accurate identification and
      classification of certain lymphoid and hematopoietic disorders; however, the
      value of electron microscopy in the diagnosis and clinical management of platelet
      pathology is less well defined. Electron microscopy has been used to evaluate
      inherited platelet disorders. In these disorders, certain platelet structural
      defects can be characteristic. Recently, we investigated the ultrastructural
      morphology and immunogold localization of IgG in platelets from patients with
      idiopathic thrombocytopenic purpura (ITP). The accelerated platelet destruction
      of ITP is mediated by antiplatelet autoantibodies directed against platelet
      surface glycoproteins and by the functional capacity of the reticuloendothelial
      system. The basic dysregulation that occurs in these patients remains
      unexplained. Traditionally, laboratory investigation of ITP has focused on the
      development of serologic assays to measure the autoantibodies. As an alternative
      investigative approach, determination of the immunomorphologic characteristics of
      platelet-associated IgG (PAIgG) in ITP platelets may prove useful in the
      diagnosis or clinical management of patients with ITP. Our results showed that
      the ultrastructural morphology of ITP platelets is similar to that observed for
      normal platelets. No structural abnormalities are observed in ITP platelets.
      Immunogold labeling of IgG within alpha-granules of ITP platelets is
      significantly higher than that of normal platelets. Additionally, in some ITP
      platelets, immunogold labeling is also observed on the platelet surface and
      within channels of the open-cannalicular system. In comparison, immunogold
      labeling of these structures in normal platelets, is rare, or absent. In
      conclusion, electron microscopic studies should contribute to furthering our
      understanding of this common autoimmune disorder, and may provide possible
      biological explanations for the increased levels of PAIgG in platelets from
      patients with ITP.

PMID- 10942213
TI  - Analogous structural motifs in myelin basic protein and in MARCKS.
AB  - Myelin basic protein (MBP) and myristoylated alanine-rich C-kinase substrate
      (MARCKS) are similar in terms of having extended conformations regulated by their
      environment (i.e., solubilised or lipid-associated), N-terminal modifications, a
      dual nature of interactions with lipids, binding to actin and Ca2+-calmodulin,
      and being substrates for different kinds of protein kinases. The further sequence
      similarities of segments of MBP with lipid effector regions of MARCKS, and
      numerous reports in the literature, support the thesis that some developmental
      isoform of MBP functions in signal transduction.

PMID- 10942217
TI  - Can drugs cause autoimmune thrombocytopenic purpura?
AB  - A wide range of medications can cause life-threatening immune thrombocytopenia
      (ITP), hemolytic anemia, or neutropenia in sensitive individuals. The antibodies
      associated with these conditions usually require soluble drug to be present in
      order to react with the cell membrane glycoproteins for which they are specific.
      However, some patients make drug-independent antibodies (autoantibodies) as well.
      Occasionally, only autoantibodies are produced following exposure to a drug.
      Although drugs and other small molecules can become conjugated to proteins in
      vivo, which may induce an immune response, only fragmentary information is
      available to explain how exogenous substances sometimes perturb the immune system
      in such a way that antibodies capable of causing immune cytopenia are produced.
      Platelets are affected by drug-induced antibodies more often than any other blood
      element. For many drug-induced thrombocytopenias, the targeted membrane
      glycoproteins are readily accessible for laboratory investigation and methods for
      detecting the responsible antibodies are well developed. Techniques for studying
      cellular aspects of the immune response induced by drugs through in vitro
      manipulation of T and B lymphocytes are also advancing rapidly. Studies of drug
      induced ITP may provide clues to the general mechanisms whereby drugs and other
      xenobiotics induce immune diseases. Clinicians should consider the possibility of
      an exogenous trigger in patients who present with apparent autoimmune
      thrombocytopenia.

PMID- 10942218
TI  - Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura.
AB  - Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which
      antiplatelet autoantibodies bind to antigens on the surface of platelets,
      resulting in their destruction. The newer antigen-specific (phase III) assays can
      detect platelet-associated and plasma autoantibodies in approximately 75% and 50%
      of patients, respectively. Antiplatelet autoantibodies bind to both platelets and
      megakaryocytes and preliminary evidence suggests that they not only cause
      platelet destruction but can also decrease platelet production either by
      interfering with megakaryocyte proliferation/maturation or by causing
      intramedullary platelet destruction. Autoantibodies are capable of activating
      complement and causing platelet phagocytosis both in vitro and in vivo. Many
      platelet-associated and plasma autoantibodies from ITP patients are light chain
      restricted, which suggests a clonal origin. Approximately 75% of platelet
      autoantigens are localized to either the platelet glycoprotein (GP) IIb/IIIa or
      Ib/IX complex. Inhibition of the binding of autoantibodies from several ITP
      patients by either another ITP autoantibody or by a monoclonal anti-GPIIb/IIIa
      antibody suggests that the antigenic repertoire in chronic ITP may be limited.
      Most autoantigens on GPIIb/IIIa appear to be conformational since they are
      dependent on the presence of divalent cations. A variety of new investigative
      techniques have localized a few autoantigens to specific regions of the
      cytoplasmic or extracellular regions of both GPIIb/IIIa and GPIb/IX.

PMID- 10942219
TI  - Advances in the diagnosis of idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) remains a clinical diagnosis made by
      the exclusion of other causes of thrombocytopenia. It is based on the patient's
      history, physical examination, and complete blood cell count, as well as
      examination of the blood film. Over the last four decades, a number of platelet
      antibody tests have been developed to aid the diagnosis of ITP. They can be
      divided chronologically into three groups. Phase I assays measure a functional
      change in control platelets after incubation with test serum. Because their
      sensitivity and specificity are low, they are no longer used to diagnose ITP.
      Phase II assays measure platelet-associated IgG by three different approaches.
      They lack the ability to differentiate between pathologic and nonpathologic
      platelet-associated IgGs. These assays are sensitive (80% to 90%) but their
      specificity is too low for them to be diagnostically useful. Phase III assays are
      the latest development in platelet serology testing. They measure glycoprotein
      specific platelet antibodies by different approaches, namely, immunoblot,
      immunoprecipitation, and glycoprotein immobilization. Despite their high
      specificity, they suffer from low sensitivity (47% to 60%), which must be
      improved if they are to be clinically useful for the diagnosis of ITP.

PMID- 10942220
TI  - Fc receptor blockade and immune thrombocytopenic purpura.
AB  - Inhibition of antibody-coated platelet destruction in patients with immune
      thrombocytopenic purpura (ITP) is a well-known mechanism of treatment effect. A
      number of interventions that would ameliorate the thrombocytopenic effect of ITP
      patient plasma when infused into normal recipients were demonstrated in 1965.
      Subsequently, the antibody-coated chromium-labeled red blood cell clearance study
      was developed to allow direct in vivo assessment of Fc receptor (FcR) blockade.
      This was first demonstrated for corticosteroids but more extensive investigation
      began with the study of intravenous infusions of gammaglobulin (IVIg). The
      unequivocal demonstration of FcR blockade following IVIg Initiated novel
      approaches. One involved the infusion of a monoclonal anti-FcRIII ligand-blocking
      antibody into patients with refractory ITP. The efficacy of this treatment
      demonstrated that FcR blockade was not an epiphenomenon but rather an important
      mechanism of the increase in the platelet count in patients with ITP.
      Confirmation of its importance was obtained from the infusion of intravenous (IV)
      anti-D and the use of the isolated Fc piece of IgG. Recent studies have begun to
      explore the possibility of a monoclonal anti-FcRI and monoclonal anti-Ds. In
      summary, FcR blockade is an important mechanism of treatment effect in patients
      with ITP. Cytokine release as a consequence of this interaction and other
      immunomodulatory effects have only begun to be studied.

PMID- 10942221
TI  - Laparoscopic splenectomy in chronic idiopathic thrombocytopenic purpura.
AB  - Splenectomy remains the definitive treatment for idiopathic thrombocytopenic
      purpura (ITP). Issues related to timing of splenectomy, perioperative management
      of platelet count, deep vein thrombosis prophylaxis, and preoperative vaccination
      are not standardized. Predicting the outcome of splenectomy is desirable but,
      again, consistent evidence for a particular approach is lacking. Laparoscopic
      splenectomy, first introduced in 1991, has removed some of the barriers to
      acceptance of splenectomy and may well change its place in the various treatment
      algorithms. This article reviews current knowledge with respect to laparoscopic
      splenectomy and provides an analysis of current evidence regarding issues of
      safety, efficacy, and cost effectiveness. Surgical technique is briefly reviewed.
      The information is drawn from a comprehensive analysis of the literature, as well
      as my own large experience with laparoscopic splenectomy, the majority of which
      has been focused on laparoscopic splenectomy for ITP.

PMID- 10942222
TI  - Management of idiopathic thrombocytopenic purpura in pregnancy.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a relatively common autoimmune
      disorder among women of child-bearing age. It has a frequency of approximately
      one to two per 1,000 live births, accounting for about 3% of all cases of
      maternal thrombocytopenia at delivery. ITP in pregnancy necessitates the
      management of two patients, the mother and her baby; hence, the close
      collaboration of a multidisciplinary group composed of a hematologist,
      obstetrician, and pediatrician is essential. Our understanding of
      thrombocytopenia in pregnancy has evolved considerably over the last decade, yet
      the optimal diagnostic and treatment strategies for ITP in pregnancy continues to
      create controversy. In reviewing the recent literature, there is resurgence in
      the trend towards treating these patients in a more conservative fashion. This
      review will summarize the current approach to the diagnosis of ITP in pregnancy,
      as well as explore the pertinent and controversial issues of investigation and
      management.

PMID- 10942223
TI  - Management of patients with chronic, refractory idiopathic thrombocytopenic
      purpura.
AB  - Chronic refractory idiopathic thrombocytopenic purpura (ITP) is defined as ITP
      with persistent thrombocytopenia despite conventional initial management with
      prednisone and splenectomy. Rare in children, It may occur in as many as one
      third of adults with ITP. The goal of treatment is not cure of the ITP, but only
      to achieve a safe platelet count, which is arbitrarily assumed to be greater than
      30,000 to 50,000/microL. The risk for major bleeding seems great only when the
      platelet count is less than 10,000/microL. Treatment of patients with moderate
      thrombocytopenia and no clinically important bleeding symptoms should be avoided.
      There is no accepted algorithm for management of patients with chronic refractory
      ITP. Observation without specific treatment must be considered a cornerstone of
      management. Combination regimens of Immunosuppressive agents may be required for
      patients with severe and symptomatic thrombocytopenia. Additional supportive care
      measures are also important.

PMID- 10942224
TI  - Approach to the investigation and management of immune thrombocytopenic purpura
      in children.
AB  - Childhood immune thrombocytopenic purpura (ITP) is typically a benign, self
      limiting disorder occurring in young (<10 years of age) previously healthy
      children. More than 80% of such children enter a complete sustained remission
      within a few weeks to a few months of initial presentation, irrespective of any
      therapy given. The major concern is the small but finite (0.1 to 0.9%) risk of
      intracranial hemorrhage, which occurs in children with very low platelet counts
      (<20 x 10(9)/L), and is the justification for treatment to increase the
      circulating platelet count. Effective treatment strategies are single-dose
      intravenous immunoglobulin G (IVIgG; approximately 1 g/kg) and medium to high
      dose corticosteroids, administered orally or parenterally. The necessity for
      initial bone marrow aspiration and hospitalization continues to be debated. In
      children with chronic ITP, defined by persistence of thrombocytopenia for > or =6
      months, splenectomy should be considered for the relatively small subgroup with
      symptomatic, severe thrombocytopenia who have either failed an adequate trial (>
      or = 12 months) of primary therapy (IVIgG, intravenous anti-D, corticosteroids)
      or are intolerant of such therapy. Laparoscopic splenectomy is preferred over
      open splenectomy. Children who fail to respond to splenectomy ( < or = 20% of
      cases) should be evaluated for the presence of accessory spleens; their
      management is often difficult and must be individualized. In severe refractory
      cases, second-line therapies (such as azathioprine or vinca alkaloids) need to be
      considered. Secondary ITP in children is relatively rare and is sometimes
      associated with other autoimmune cytopenias (Evan's syndrome, ITP with autoimmune
      neutropenia). These cases often respond poorly to conventional medical therapies
      and response rates to splenectomy are considerably lower than in children with
      primary chronic ITP.

PMID- 10942226
TI  - Programmed cell death regulation: basic mechanisms and therapeutic opportunities.
AB  - The molecular mechanisms responsible for induction or inhibition of apoptosis
      signal transduction have been intensively investigated during the past few years.
      Information gained from mechanistic studies and from structural analysis of
      apoptosis regulatory proteins has provided considerable insight into the pathways
      that determine whether a cell will live or die. Many of these advances were
      recently presented at the American Association for Cancer Research Special
      Conference on 'Programmed Cell Death Regulation: Basic Mechanisms and Therapeutic
      Opportunities'. This mini-review will discuss the current state of knowledge
      regarding apoptosis signaling pathways and the function of apoptosis regulatory
      proteins.

PMID- 10942225
TI  - Anti-idiotype vaccines for human follicular lymphoma.
AB  - Cancer vaccines are conceived as therapeutic tools, in contrast to the
      prophylactic vaccines that have resolved the problem of a number of infectious
      diseases in a highly cost-effective way. Over the last decade, anti-idiotype
      vaccines for human follicular lymphoma have started to come into their own.
      Whereas 10 years ago it was not even known whether patients could be immunized
      against an antigen of their own tumor, a phase III clinical trial based on this
      finding is now already underway. The rapidity of this development encourages the
      hope that active immunotherapy may become decisive in oncology sooner than
      expected. Many important results have already been achieved. These include
      evidence of vaccine-induced, tumor-specific humoral and cellular responses along
      with the first documented molecular remissions following vaccination. Crucial
      questions still awaiting an answer include: do Id vaccines actually cure at least
      a fraction of FL patients? What is the most effective vaccine formulation? Is it
      possible to reduce the workload involved in producing an effective Id vaccine?

PMID- 10942227
TI  - Duration of second complete remission compared with first complete remission in
      patients with acute myeloid leukemia. Eastern Cooperative Oncology Group.
AB  - The prognosis for patients with acute myeloid leukemia in first relapse is
      generally poor. The ability to induce a second complete remission (CR) with the
      same chemotherapy used in initial induction therapy is limited. Remission
      inversion rate, defined as achieving a longer second CR than the first CR in
      response to standard chemotherapy for relapse, is important in assessing studies
      of novel chemotherapy or immunologic treatment strategies for patients with
      relapsed disease. One hundred and twenty-four patients entered on two Eastern
      Cooperative Oncology Group (ECOG) studies for patients with relapsed AML were
      analyzed to determine the remission inversion rate. Twenty-two of the 124
      patients (18%; 95% confidence interval 12-26%) experienced a longer second CR
      duration than the first CR duration by at least 2 months. Inversion of CR
      duration is thus not a rare event. The inversion frequency reported here
      establishes a baseline upon which future studies in relapsed disease need to be
      defined.

PMID- 10942228
TI  - Low-dose cytarabine maintenance therapy vs observation after remission induction
      in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial
      (E5483).
AB  - The Eastern Cooperative Oncology Group (ECOG) conducted a prospective phase III
      study in patients with relapsed/refractory acute myeloid leukemia (AML) to
      evaluate whether administration of repeated courses of low-dose cytarabine (LDAC)
      maintenance therapy after induction of complete remission in advanced AML would
      improve disease-free and overall survival. Patients with AML in second/later
      relapse or refractory disease were first treated with a combination of high-dose
      cytarabine and amsacrine. Those who achieved complete remission were then
      randomized to observation or to receive LDAC, 10 mg/m2 subcutaneously twice a day
      x2 21 days every 2 months until relapse occurred. Of 86 patients eligible for
      randomization, 41 patients were assigned to receive LDAC and 45 patients to
      observation. The median disease-free survival was 7.4 months for patients
      assigned to LDAC compared to 3.3 months for patients receiving no additional
      therapy, P= 0.084. The median survival from randomization was 10.9 months and 7.0
      months for patients receiving LDAC maintenance chemotherapy and observation,
      respectively (P= 0.615). The data from this study suggest that LDAC maintenance
      therapy given to patients with advanced AML who achieve complete remission can
      increase disease-free survival compared to observation, but does not improve
      overall survival. Nevertheless, because of the ineffectiveness and toxicity of
      intensive post-remission chemotherapy in this circumstance, LDAC maintenance
      therapy, a tolerable outpatient regimen, offers the potential for improved
      quality of life.

PMID- 10942229
TI  - Pilot studies of species-specific chemotherapy of childhood acute lymphoblastic
      leukemia using genotype and immunophenotype.
AB  - Genotype and immunophenotype can be used to define biological species of acute
      lymphoblastic leukemia (ALL). The purpose of these two pilot studies, conducted
      between 1986 and 1994, was to explore the feasibility and acceptability of
      classifying ALL in this manner for selection of treatment rather than using
      conventional risk for failure factors such as age and initial white blood cell
      count. The possibility that conventional risk factors would be overcome and
      survival improved by this approach was also considered. Flow cytometry and
      chromosome analysis were used to classify the ALL of 150 children into one of
      five biologic categories as defined by cell surface antigens, DNA index and
      chromosome number and arrangement. Chemotherapy regimens depended on the assigned
      category. There was no provision for cranial irradiation and use of alkylating
      agents, anthracyclines and epipodophyllotoxins was restricted in order to reduce
      risk of late adverse sequelae. All patients are included in the analysis
      regardless of presenting condition or adherence to protocol. The majority of
      patients were Mexican-American or African-American. Eight-year event-free
      survival (EFS) is 60.7% (+/-4%) and 8-year overall survival (OAS) 72.6% (+/
      3.7%). EFS and OAS varied significantly among the biologic categories despite
      differences in chemotherapy regimens. When the patients with B-precursor ALL were
      retrospectively classified by current Pediatric Oncology Group (POG) criteria, 8
      year EFS was 82% (+/-7.3%) for the good risk group, 68.9% (+/-5.9%) for the
      standard risk and 48.8% (+/-7.6%) for the poor risk, all significant differences.
      However, when retrospectively classified according to the Rome/NCI prognostic
      criteria the 8-year EFS for standard risk patients was 69.1% (+/-5.1%) and for
      high risk 58.8% (+/-6.9%), not a statistically significant difference. Numbers of
      T cell and B cell patients are too few for comparison. Gender and ethnicity
      influenced survival as in treatment based on prognostic factors. Initial central
      nervous system (CNS) relapse occurred in five patients (3%) and combined CNS and
      hematological relapse in six (3%). Factors significantly associated with CNS and
      combined relapse were leukemic pleocytosis in the initial CSF sample, pro-B
      immunophenotype and DNA index <1.16, but not initial white blood cell count. Only
      three survivors appear to have serious late adverse sequelae, the only neurologic
      the result of asparaginase-induced cortical vein thrombosis. The results suggest
      that use of biologic species as defined by immunophenotype and genotype to select
      therapy of ALL is feasible and acceptable but under the conditions of these
      studies offered no apparent therapeutic advantage over conventional risk
      grouping. However, the introduction of molecular genotyping and novel gene
      targeted therapeutic agents justify further exploration of this approach.

PMID- 10942230
TI  - Double induction strategy including high dose cytarabine in combination with all
      trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic
      leukemia. German AML Cooperative Group.
AB  - A prospective multicenter study was performed to investigate the clinical and
      molecular results of intensified double induction therapy including high-dose
      cytarabine (ara-C) in combination with ATRA in newly diagnosed acute
      promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance
      therapy. Fifty-one patients, diagnosed and monitored from December 1994 to June
      1999, were evaluated. The median age was 43 (16-60) years. The morphologic
      diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients
      the initial white blood cell counts were > or =5 x 10(9)/l. The cytogenetic or
      molecular proof of the translocation t(15;17) was a mandatory prerequisite for
      eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of
      the PML/RARalpha transcript in 45 cases. The rate of complete hematological
      remission was 92% and the early death rate 8%. Monitoring of minimal residual
      disease by RT-PCR of PML/RARalpha (sensitivity 10(-4)) showed negativity in 29 of
      32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation,
      and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18
      months after diagnosis, respectively. After a median follow-up of 27 months, the
      estimated actuarial 2 years overall and event-free survival were both 88% (79,
      97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic
      efficacy of this treatment strategy is demonstrated by a rapid and extensive
      reduction of the malignant clone and by a low relapse rate. The results suggest
      that the intensity of the induction chemotherapy combined with ATRA is one of the
      factors which may have a critical influence on the outcome of APL. A randomized
      trial should assess the value of an induction therapy including ATRA and high
      dose ara-C in comparison to standard-dose ara-C.

PMID- 10942231
TI  - Long-term follow-up confirms the benefit of all-trans retinoic acid in acute
      promyelocytic leukemia. European APL group.
AB  - First results of a randomized trial (APL91 trial) and other randomized or non
      randomized studies have shown that ATRA followed by chemotherapy significantly
      increased event-free survival (EFS) and survival, and decreased the incidence of
      relapse by comparison to chemotherapy alone in newly diagnosed APL. We present
      here long-term follow-up of the APL91 trial. In this trial, 101 patients had been
      randomized between ATRA followed by three courses of daunorubicin-AraC
      chemotherapy (ATRA group) and the same chemotherapy alone (chemotherapy group).
      Results were reanalyzed 73 months after closing of patient entry. Updated results
      of APL 91 trial found a Kaplan-Meier estimate of EFS and relapse rate at 4 years
      of 63% and 31% in the ATRA group, as compared to 17% and 78% in the chemotherapy
      group (P= 10(-4) and relative risk 2.95, P= 10(-4) and relative risk 3.68,
      respectively). Kaplan-Meier survival at 4 years was 76% in the ATRA group and 49%
      in the chemotherapy group (P= 0.026, relative risk 2.7). In the chemotherapy
      group, seven of the 27 relapses occurred after 18 months, but no relapse was seen
      after 43 months. In the ATRA group, four of the 17 relapses occurred after 18
      months, including two late relapses (at 58 and 74 months). In the chemotherapy
      group, 23 of the 25 patients who relapsed achieved a second CR with ATRA, and the
      Kaplan-Meier estimate of second relapse was 40% at 30 months. In the ATRA group,
      the 10 patients who relapsed and were retreated with ATRA achieved a second CR.
      In conclusion, long-term results of APL91 trial confirm the superiority of the
      combination of ATRA and chemotherapy over chemotherapy alone in newly diagnosed
      APL, and that ATRA should be incorporated in the front-line treatment of APL.

PMID- 10942232
TI  - Erythropoietic reconstitution, macrophages and reticulin fibrosis in bone marrow
      specimens of CML patients following allogeneic transplantation.
AB  - A clinicopathological study was conducted on 351 bone marrow trephine biopsies
      derived from 124 patients with chronic myeloid leukemia (CML) at standardized
      endpoints before and after allogeneic bone marrow transplantation (BMT). The
      purpose was to investigate quantitative changes of the nucleated erythroid
      precursor cell population and other associated features such as resident bone
      marrow macrophages and myelofibrosis and to elucidate their relevance on
      engraftment parameters. Monoclonal antibodies were applied for the identification
      of erythroid precursors and the labeling of mature macrophages; argyrophilic
      (reticulin-collagen) fibers were demonstrated by a silver impregnation technique.
      Following morphometric analysis of the pregraft bone marrow specimens statistical
      evaluation was in line with an adverse correlation between early to moderate
      reticulin fibrosis and amount of erythropoiesis. Moreover, a significant
      relationship was calculable between numbers of erythroid precursors and CD68+
      macrophages. After myelo-ablative therapy and BMT a pronounced decrease in
      cellularity and in the quantity of erythropoiesis was found. Comparable with the
      pregraft samples, a significant association between erythroid precursors and
      macrophages could be determined in the regenerating donor bone marrow. A
      pretransplant relevant reduction of the red cell lineage and a manifest
      (reticulin) myelofibrosis indicating an advanced stage of disease were
      accompanied by a significant delay to reach transfusion independence. This result
      was further supported by comparable findings in trephine biopsies performed in
      the early post-transplant period (second month after BMT). Corresponding
      examinations revealed an enhancement of fiber density and a decrease in
      erythropoiesis in those patients who did not conform with the usually accepted
      criteria for successful engraftment. In conclusion, compelling evidence has been
      produced that a significantly reduced amount of erythroid precursors, which is
      usually associated with myelofibrosis in the pretransplant bone marrow, exerts an
      impairment to undisturbed hematopoietic reconstitution. Moreover, a close spatial
      and numerical relationship between the erythroid lineage and resident (mature)
      macrophages is observable, in particular in the state of regeneration after BMT.

PMID- 10942233
TI  - Participation of granulocyte colony-stimulating factor in the growth regulation
      of leukemia cells from Philadelphia chromosome-positive acute leukemia and blast
      crisis of chronic myeloid leukemia.
AB  - Granulocyte colony-stimulating factor (G-CSF) has been shown to support the
      growth of multipotential hematopoietic stem cells in addition to the cells of
      neutrophilic lineage. Philadelphia chromosome (Ph1)-positive leukemia has its
      origin in the hematopoietic stem cell. In the present study, we demonstrated that
      the proliferation of leukemic cells from chronic myeloid leukemia in blast crisis
      (CML-BC) and Ph1-positive acute lymphoblastic leukemia (ALL) cases is frequently
      stimulated with G-CSF in vitro. We next studied a total of 12 leukemic cell lines
      established from CML-BC (n= 6) and Ph1-positive acute leukemia (n= 6): four
      'myeloid', five 'biphenotypic', and three 'lymphoid' types. All cell lines
      expressed G-CSF receptor (G-CSFR) in flow cytometric analysis, but their
      proliferative response to G-CSF in 3H-thymidine incorporation assay varied. The
      'biphenotypic' cell lines expressed G-CSFR at higher levels and showed the most
      pronounced response to G-CSF. The 'lymphoid' cell lines showed intermediate G
      CSFR expression with the modest response to G-CSF. Unexpectedly, 'myeloid' cell
      lines showed lower G-CSFR expression and lower G-CSF response compared with
      'biphenotypic' cell lines. In three of four 'myeloid' cell lines, proliferation
      was partially inhibited by an addition of anti-G-CSF neutralizing monoclonal
      antibody into culture medium. Further, the % inhibition of 3H-thymidine uptake of
      cell lines positively correlated with the amount of their intracellular G-CSF
      measured by enzyme immunoassay, suggesting an autocrine growth mechanism via the
      G-CSF/G-CSFR interaction. These results suggest that G-CSF play an important role
      in the growth regulation of leukemia cells from Ph1-positive acute leukemia and
      CML-BC.

PMID- 10942235
TI  - Increase in mutant frequencies in mice expressing the BCR-ABL activated tyrosine
      kinase.
AB  - The acquisition of the Philadelphia (Ph) chromosome (or BCR-ABL translocation)
      represents a detrimental pathophysiological event in humans. The activated
      tyrosine kinases, which are produced by this translocation, are associated with
      fatal hematological malignancies. The initial molecular dissection of BCR-ABL has
      linked the expression of this constitutively activated kinase with enhanced
      genomic instability. We directly evaluated the consequence of BCR-ABL expression
      on genomic instability using the Big Blue in vivo mutagenesis mouse system. We
      report that the expression of BCR-ABL in both spleens and kidneys confers a
      mutator phenotype represented by a statistically significant elevation in mutant
      frequencies.

PMID- 10942234
TI  - Combination of interferon alpha with either Ara-C or ATRA in vitro reduces the
      selective action of interferon against CML CFU-GM.
AB  - Although interferon (IFN)-alpha has no specific inhibitory effect on the plating
      efficiency of granulocyte-macrophage colony-forming cells (CFU-GM) from patients
      with chronic myeloid leukaemia (CML), it does selectively inhibit the replating
      ability (secondary colony formation) of CML CFU-GM. Thus, amplification of CFU-GM
      may be a target for IFN-alpha and other agents used in the treatment of CML. Here
      we examined whether cytarabine (Ara-C) or all-trans retinoic acid (ATRA) exert
      similar effects and whether they might in combination with IFN-alpha enhance its
      efficacy. We found that Ara-C preferentially inhibits the formation of CML CFU-GM
      compared to normal CFU-GM, but this inhibition was not increased by addition of
      IFN-alpha. When Ara-C was added to cultures containing IFN-alpha, the inhibition
      of replating by CML progenitors was abrogated. ATRA increased significantly the
      plating efficiency of normal CFU-GM. The addition of IFN-alpha to ATRA had no
      effect on CML or normal colony numbers. However, addition of ATRA to cultures
      containing IFN-alpha reversed the selective inhibition of CML CFU-GM replating
      seen in cultures containing IFN-alpha alone. In four IFN-alpha/Ara-C experiments,
      secondary CML patient-derived colonies were examined by fluorescence in situ
      hybridisation (FISH). All of them were Ph chromosome positive. No significant
      effects on CFU-GM production were observed when CML primitive haemopoietic
      progenitor cells were investigated in a delta (delta) assay. Thus we conclude
      that combining IFN-alpha with Ara-C or ATRA neutralises the effect of IFN-alpha
      on CML CFU-GM. This observation provides a rationale for treating patients with
      alternating courses of IFN-alpha and Ara-C or ATRA, rather than giving either of
      these two agents in combination with IFN-alpha.

PMID- 10942236
TI  - Inhibition of RNA transcription: a biochemical mechanism of action against
      chronic lymphocytic leukemia cells by fludarabine.
AB  - Fludarabine is a nucleotide analog effective in the clinical treatment of chronic
      lymphocytic leukemia (CLL) and other indolent lymphocytic malignancies. Although
      the incorporation of fludarabine into DNA is a key event in causing cytotoxicity
      in proliferating leukemia cells, the precise mechanisms by which fludarabine
      kills CLL cells remain unclear because of the quiescent nature of this
      malignancy. The present study demonstrated that inhibition of RNA transcription
      correlated significantly with the cytotoxic action of fludarabine in CLL cells.
      In contrast, suppression of the low level of DNA synthesis did not affect the
      survival of the leukemia cells. In addition, inhibition of fludarabine
      incorporation into cellular DNA through repair synthesis in CLL cells did not
      alter the cytotoxicity of this drug. Rather, inhibition of RNA synthesis by
      fludarabine led to a specific diminishment of certain cellular proteins from CLL
      cells. The combination of fludarabine with another RNA synthesis inhibitor,
      actinomycin D, or with the protein synthesis inhibitor, puromycin, substantially
      enhanced the cytotoxic activity against CLL cells. These results suggest that
      termination of mRNA transcription and the consequent depletion of proteins
      required for cell survival may be a novel biochemical mechanism of action of
      fludarabine in CLL cells. Thus, inhibition of RNA/protein synthesis may provide a
      new therapeutic strategy for the treatment of CLL patients.

PMID- 10942237
TI  - Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia.
AB  - Recent studies have shown that angiogenesis may be involved in the pathogenesis
      of hematopoietic malignancies, apart from its well-characterized role in the
      growth and metastasis of solid tumors. In this study, we quantified the degree of
      angiogenesis in B cell chronic lymphocytic leukemia (B-CLL) by measuring the
      microvessel density and hotspot density in bone marrow trephine biopsy sections
      with B-CLL involvement (n = 12) and compared it to normal bone marrow sections (n
      = 11). The B-CLL samples had a mean microvessel count/high power field (hpf) of
      7.64 while the control samples had a mean microvessel count/hpf of 2.11 (P =
      0.0001). The mean hotspot density in the B-CLL sections (14.83/hotspot) was also
      significantly higher (P = 0.0008) than the mean hotspot density in control bone
      marrow sections (7.09/hotspot). Both the microvessel density and hotspot density
      correlated positively with the clinical stage of the B-CLL patients. In a
      separate cohort of B-CLL patients, the median urine level of the angiogenic
      peptide, basic fibroblast growth factor (2216.5 pg/g, n = 14), was significantly
      higher (P = 0.0001) than the bFGF level in normal controls (1,084 pg/g, n = 58).
      These results indicate that angiogenesis may be involved in the pathogenesis of B
      CLL.

PMID- 10942238
TI  - Improved assessment of minimal residual disease in B cell malignancies using
      fluorogenic consensus probes for real-time quantitative PCR.
AB  - PCR of clonally rearranged immunoglobulin heavy chain (IgH) gene sequences is
      increasingly used for detection of minimal residual disease (MRD) in lymphoid
      malignancies. Inherent quantitating problems are the main drawbacks of
      traditional PCR technologies. These limitations have been overcome by the
      recently developed real-time quantitative PCR (RQ PCR) technology. However,
      clinical application of the few published RQ PCR assays targeting immune gene
      rearrangements is hampered by the expensive and time-consuming need for
      individual hybridization probes for each patient. We have developed a new RQ PCR
      strategy targeting clonally rearranged IgH sequences that solves this problem.
      The method uses only two different JH hybridization probes and four downstream JH
      primers homologous to consensus germline JH gene segments. In combination with an
      allele-specific upstream (ASO) primer the consensus JH probes and primers allow
      quantitation of about 90% of possible IgH rearrangements. In a series of 22 B
      lineage ALL the new assay allowed the detection of one to 10 blasts in a
      background of 10(5) normal cells. To prove the clinical utility we quantified MRD
      in 23 follow-up samples of six ALL patients with the new assay in comparison with
      a published RQ PCR technique that used individually designed primer/probe sets.
      We showed that the sensitivity of the new RQ PCR assay was slightly higher for
      four of the six cases and about 100-fold higher for one case, enabling detection
      of an increasing MRD level as an indicator of subsequent relapse 44 weeks earlier
      compared to the ASO probe assay in this particular patient. The results suggest,
      that the novel RQ PCR assay is a rapid, technically simple, reliable, and
      sensitive alternative to traditional quantification assays and simplifies current
      approaches of monitoring MRD in clinical trials.

PMID- 10942239
TI  - Application of germline IGH probes in real-time quantitative PCR for the
      detection of minimal residual disease in acute lymphoblastic leukemia.
AB  - Large-scale clinical studies on detection of minimal residual disease (MRD) in
      acute lymphoblastic leukemia (ALL) have shown that quantification of MRD levels
      is needed for reliable MRD-based risk group classification. Recently, we have
      shown that 'real-time' quantitative PCR (RQ-PCR) can be applied for this purpose
      using patient-specific immunoglobulin (Ig) and T cell receptor (TCR) gene
      rearrangements as PCR targets with TaqMan probes at the position of the
      junctional region and two germline primers. Now, we tested an alternative
      approach on 35 immunoglobulin heavy chain (IGH) gene rearrangements, by designing
      three germline JH TaqMan probes to be used in combination with one of six
      corresponding germline JH primers and one allele specific oligonucleotide (ASO)
      primer complementary to the junctional region. In nine cases in which both
      approaches were compared, at least similar (n = 4) or slightly higher (n= 5)
      maximal sensitivities were obtained using an ASO primer. The ASO primer approach
      reached maximal sensitivities of at least 10(-4) in 33 out of 35 IGH
      rearrangements. The reproducible range for accurate quantification spanned four
      to five orders of magnitude in 31 out of 35 cases. In 13 out of 35 rearrangements
      the stringency of PCR conditions had to be increased to remove or diminish
      background signals; this only concerned the frequently occurring JH4, JH5 and JH6
      gene rearrangements. After optimization of the conditions (mainly by increasing
      the annealing temperature), only occasional aspecific amplification signals were
      observed at high threshold cycle (CT) values above 42 cycles and at least six
      cycles above the CT value of the detection limit. Hence, these rare aspecific
      signals could be easily discriminated from specific signals. We conclude that the
      here presented set of three germline JH Taq-Man probes and six corresponding
      germline JH primers can be used to develop patient-specific RQ-PCR assays, which
      allow accurate and sensitive MRD analysis in almost all IGH gene rearrangements.
      These results will facilitate standardized RQ-PCR analysis for MRD detection in
      large clinical studies.

PMID- 10942240
TI  - Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab
      zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines,
      but is inactive on P-glycoprotein-expressing sublines.
AB  - Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676,
      has recently been introduced to clinics as a promising drug to treat patients
      with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of
      CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60,
      NOMO-1, NB4, NKM-1, K562, Daudi, and the multidrug-resistant sublines, NOMO-1/ADR
      and NB4/MDR, was investigated by cell cycle distribution and morphology. These
      studies were done by a video-microscopic system, DNA fragmentation, dye exclusion
      and 3H-thymidine uptake after analysis of CD33, CD34, P-glycoprotein (P-gp),
      multidrug resistance (MDR)-associated protein and lung-related protein on these
      cells. A dose-dependent, selective cytotoxic effect of CMA-676 was observed in
      cell lines that expressed CD33, and was dependent on the amount of CD33 and the
      proliferative speed of the cells. Sensitive cells were temporally arrested at the
      G2/M phase before undergoing morphological changes. CMA-676 is not effective on P
      gp-expressing multidrug-resistant sublines compared with parental cell lines. MDR
      modifiers, MS209 and PSC833, restored the cytotoxic effect of CMA-676 in P-gp
      expressing sublines. CMA-676 is a promising agent in the treatment of patients
      with AML that expresses CD33. The combined use of CMA-676 and MDR modifiers may
      increase the selective cytotoxic effect in multidrug-resistant AML.

PMID- 10942241
TI  - Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to
      lovastatin.
AB  - Lovastatin, a competitive inhibitor of HMG-CoA reductase, reportedly inhibits
      proliferation and induces apoptosis of tumor cells with MDR-1 coded P
      glycoprotein (Pgp) expression. In this study we investigated the sensitivity to
      lovastatin of eight myeloid leukemia cell lines: K562, NOMO-1, NB4 and its
      retinoic acid (RA) resistant subline NB4/RA, and their multidrug-resistant (MDR)
      sublines: K562/ADR, NOMO-1/ADR, NB4/MDR and NB4/RA/MDR. MTT and apoptosis assays
      revealed that K562/ADR, NOMO-1/ADR and NB4/RA/MDR were more sensitive to
      lovastatin than their parental cell lines, while NB4/MDR showed the same level of
      sensitivity as parental NB4 cells, which already were very sensitive to
      lovastatin. Significant elevation of transcript levels of HMG-CoA reductase was
      observed by semiquantitative RT-PCR analysis in more than three lovastatin
      sensitive MDR sublines, but not in NB4/MDR compared with the parental cell lines.
      HMG-CoA reductase mRNA levels were up-regulated more than two-fold by the
      exposure to lovastatin in all of the parental non-Pgp-expressing cell lines. In
      NB4/MDR, HMG-CoA reductase mRNA level was elevated to a similar extent as in
      parental NB4, whereas in three other MDR sublines which showed preferential
      sensitivity to lovastatin, their HMG-CoA reductase mRNA levels were not
      significantly elevated after 24- and 48-h treatment with lovastatin. These
      results indicate a connection between drug resistance and regulation of the
      mevalonate pathway, and further strengthen the clinical possibility that drug
      resistant leukemias would be susceptible to treatment with lovastatin.

PMID- 10942242
TI  - Cytotoxic and clastogenic effects of a DNA minor groove binding methyl sulfonate
      ester in mismatch repair deficient leukemic cells.
AB  - Mismatch repair deficiency contributes to tumor cell resistance to O6-guanine
      methylating compounds and to other antineoplastic agents. Here we demonstrate
      that MeOSO2(CH2)2-lexitropsin (Me-Lex), a DNA minor groove alkylating compound
      which generates mainly N3-methyladenine, has cytotoxic and clastogenic effects in
      mismatch repair-deficient leukemic cells. Moreover, MT-1 cells, which express p53
      upon drug treatment and possess low levels of 3-methylpurine DNA glycosylase
      activity, are more susceptible to cytotoxicity induced by Me-Lex, with respect to
      p53-null and 3-methylpurine DNA glycosylase-proficient Jurkat cells. In both cell
      lines, the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide, which inhibits
      base excision repair capable of removing N-methylpurines, increases cytotoxicity
      and clastogenicity induced by Me-Lex or by temozolomide, which generates low
      levels of N3-methyl adducts. The enhancing effect is more evident at low Me-Lex
      concentrations, which induce a level of DNA damage that presumably does not
      saturate the repair ability of the cells. Nuclear fragmentation induced by Me-Lex
      + 3-aminobenzamide occurs earlier than in cells treated with the single agent.
      Treatment with Me-Lex and 3-aminobenzamide results in augmented expression of p53
      protein and of the X-ray repair cross-complementing 1 transcript (a component of
      base excision repair). These results indicate that N3-methyladenine inducing
      agents, alone or combined with poly(ADP-ribose) polymerase inhibitors, could open
      up novel chemotherapeutic strategies to overcome drug resistance in mismatch
      repair-deficient leukemic cells.

PMID- 10942243
TI  - Role of the membrane form of human colony-stimulating factor-1 (CSF-1) in
      proliferation of multipotent hematopoietic FDCP-mix cells expressing human CSF-1
      receptor.
AB  - Because IL-3-dependent multipotential FDCP-Mix cells expressing human colony
      stimulating factor-1 (CSF-1) receptor did not proliferate in response to soluble
      CSF-1, we investigated whether their proliferation would be induced in co-culture
      with adherent cells expressing the membrane form of CSF-1 (MemCSF-1). FDCP-Mix
      cells with high CSF-1R expression (NAF21 cells) were placed on stromal MS-5 cells
      or STO fibroblasts expressing MemCSF-1 (2M-1 cells and STO-M2 cells,
      respectively), in absence of IL-3. NAF21 cells bound significantly to 2M-1 cells
      as compared to control FDCP-Mix cells. Adhesion of NAF21 cells was inhibited by
      anti-huCSF-1 antibodies, as well as anti-huCSF-1R antibodies. Interestingly,
      NAF21 cells proliferated on both 2M-1 and STO-M2 cells but with very different
      kinetics. Moreover, NAF21 cell proliferation was also supported by glutaraldehyde
      fixed 2M-1 cells or highly concentrated MS-5 cell culture supernatant, but not by
      CSF-1 coated on culture dishes. These results strongly suggest that MemCSF-1/CSF
      1R interaction mediates a specific adhesion of NAF21 cells to stromal cells and
      allows stimulation of hematopoietic cells by stromal cell-derived factors
      expressed in a membrane-bound form or concentrated within the extracellular
      matrix. Thus, cytokine receptors deficient in mitogenic signalling may
      nevertheless have a regulatory role in hematopoietic progenitor cell
      proliferation by acting as adhesion molecules.

PMID- 10942244
TI  - Rapid tumor formation and development of neutrophilia and splenomegaly in nude
      mice transplanted with human cells expressing human T cell leukemia virus type I
      or Tax1.
AB  - Human T cell leukemia virus type I (HTLV-I) or its transcriptional
      transactivator, Tax1, was introduced into a human osteosarcoma cell line, HOS,
      and a Moloney murine sarcoma virus-positive HOS cell line, S+L-HOS. These HTLV-I-
      or Tax1-expressing cells were injected subcutaneously into nude mice to
      investigate the effects of HTLV-I on their tumorigenicities. HOS cells did not
      form any tumors even in the presence of HTLV-I or Tax1. S+L-HOS cells did form
      small tumors in two-thirds of nude mice. Infection of S+L-HOS cells with HTLV-I,
      or transduction of Tax1 into S+L-HOS cells markedly facilitated the tumor
      formation, and the tumor-bearing mice showed marked splenomegaly and
      neutrophilia. Elevated levels of granulocyte colony-stimulating factor (G-CSF)
      were detected in sera of these mice and also in the culture supernatants of Tax1
      expressing human cells, suggesting that G-CSF in the mouse sera was produced by
      the human cells. In sera of some mice with splenomegaly and neutrophilia, high
      levels of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) were
      observed, suggesting that Tax1 produced by human cells induced mouse cells to
      produce mGM-CSF. Only S+L-HOS cell lines expressing Tax1 showed high
      tumorigenicity in nude mice. Thus, this system will be a useful model of tumor
      formation, splenomegaly and neutrophilia dependent on Tax1.

PMID- 10942245
TI  - Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis
      by green tea in animal models of human high-grade non-Hodgkin's lymphoma.
AB  - Recent reports suggest that green tea consumption may prevent or delay the growth
      of human cancer, possibly by impairing tumor invasion and/or by an anti
      angiogenic effect. In NOD/SCID mice transplanted intraperitoneally with human non
      Hodgkin's lymphoma (NHL) cell lines, Namalwa, RAP1-EIO and HS-Sultan, green tea
      prevented 50% of Namalwa tumors (P = 0.0017 by log-rank) and significantly
      inhibited RAP1-EIO and HS-Sultan tumor growth. Notably, treatment with the
      chemotherapy drug cyclophosphamide at the maximum tolerable dose was unable to
      prevent Namalwa tumor occurrence. In the three models evaluated, the frequency of
      apoptotic endothelial and tumor cells was significantly increased in mice given
      green tea compared to controls. These results support further trials in NHL to
      evaluate whether green tea, alone or in combination with chemotherapy, may delay
      or prevent disease progression.

PMID- 10942246
TI  - Mantle cell lymphoma proliferates upon IL-10 in the CD40 system.
AB  - Mantle cell lymphoma (MCL) is a B cell non-Hodgkin's lymphoma, characterized by a
      poor response to therapy and short survival. To assess the proliferative
      capacity, we cultured MCL cells, using irradiated 3T6 mouse fibroblasts
      transfected with human CD40L ('CD40 system') in the presence of different
      cytokines. Proliferation was measured by 3H-thymidine incorporation and by CFSE
      fluorescence. Thirteen out of 16 MCL cases proliferated well in the CD40 system.
      In 10 cases a strong response upon further addition of IL-10 was seen, whereas IL
      4 had an additional effect in only four cases. CFSE staining of cells before and
      after culture showed an increased number of cell divisions in the IL-10/CD40L
      stimulated cells. The MCL cells remained CD5+CD19+. Neither plasma cell
      differentiation nor isotype switching was seen. The light chain expression was
      strictly monoclonal. IL-1beta, IL-2, IL-6, G-CSF and GM-CSF did not stimulate MCL
      proliferation. IL-10 receptor expression correlated with the response to IL-10 in
      the culture system and the effect of added IL-10 could be blocked by antibodies
      directed against IL-10 and the IL-10 receptor. Autocrine IL-10 production by the
      MCL cells was detected in eight of 10 cases tested. IL-10 receptor blocking
      decreased proliferation when no exogenous IL-10 was used in four of seven cases
      tested. EBV assessed by EBER in situ hybridization was not detected in six cases
      tested. In conclusion, MCL can successfully be cultured upon CD40 stimulation if
      3T6 CD40L+ cells are used. In this context IL-10 is a costimulatory factor. IL-10
      receptor expression seems to correlate with response to CD40 crosslinking and IL
      10. Autocrine IL-10 production might play a role in the proliferation of this
      lymphoma. This culture system may be useful to test new treatment strategies for
      this, thus far, therapy-resistant lymphoma.

PMID- 10942247
TI  - BCL10 is not the gene inactivated by mutation in the 1p22 deletion region in
      mantle cell lymphoma.
AB  - The BCL10 gene has recently been cloned from the 1p22 breakpoint of the
      translocation t(1 ;14)(p22;q32) observed in mucosa-associated lymphoid tissue
      (MALT) lymphoma. BCL10 was shown to be a proapoptotic-signaling gene encoding a
      protein that contains an amino-terminal caspase recruitment domain (CARD).
      Mutations within the BCL10 coding region resulting in truncated BCL10 proteins
      with loss of their proapoptotic function and preservation of their NF-kappaB
      activating function were detected in MALT lymphoma. Based on these findings it
      was proposed that BCL10 might have tumor suppressor function. Deletions involving
      1p22 are commonly observed in mantle cell lymphoma (MCL). To investigate its role
      in MCL we have analyzed a series of 15 MCL for deletion and mutation of BCL10.
      Monoallelic 1p22 deletions were detected by fluorescence in situ hybridization in
      five of the 15 cases and were shown to affect BCL10 in all cases. BCL10 was
      screened for mutations by DNA sequencing of RT-PCR amplified transcripts. In none
      of the 15 MCL cases studied were mutations found in the BCL10 coding region. A
      previously reported polymorphism exhibiting a silent 24C > G substitution was
      found in eight MCL cases and in four healthy probands. A missense mutation 13G >T
      resulting in a substitution of a serine by an alanine was seen in one of the
      controls. Our results strongly suggest that BCL10 is not the candidate tumor
      suppressor gene inactivated by deletion or mutation in band 1p22 in MCL.

PMID- 10942248
TI  - The detection of contaminating clonal cells in apheresis products is related to
      response and outcome in multiple myeloma undergoing autologous peripheral blood
      stem cell transplantation.
AB  - In the present paper, we report on the use of the heteroduplex PCR technique to
      detect the presence of clonally rearranged VDJ segments of the heavy chain
      immunoglobulin gene (VDJH) in the apheresis products of patients with multiple
      myeloma (MM) undergoing autologous peripheral blood stem cell (APBSC)
      transplantation. Twenty-three out of 31 MM patients undergoing APBSC
      transplantation with VDJH segments clonally rearranged detected at diagnosis were
      included in the study. Samples of the apheresis products were PCR amplified using
      JH and VH (FRIII and FRII) consensus primers and subsequently analyzed with the
      heteroduplex technique, and compared with those obtained at diagnosis. 52% of
      cases yielded positive results (presence of clonally rearranged VDJH segments in
      at least one apheresis). The presence of positive results in the apheresis
      products was not related to any pretransplant characteristics with the exception
      of response status at transplant. Thus, while no one patient with positive
      apheresis products was in complete remission (CR), negative immunofixation,
      before the transplant, five cases (46%) with negative apheresis were already in
      CR at transplant (P = 0.01). The remaining six cases with heteroduplex PCR
      negative apheresis were in partial remission before transplant. Patients with
      clonally free products were more likely to obtain CR following transplant (64% vs
      17%, P= 0.02) and a longer progression-free survival, (40 months in patients
      transplanted with polyclonal products vs 20 with monoclonal ones, P = 0.03).
      These results were consistent when the overall survival was considered, since it
      was better in those patients with negative apheresis than it was in those with
      positive (83% vs 36% at 5 years from diagnosis, P= 0.01). These findings indicate
      that the presence of clonality rearranged VDJH segments is related to the
      response and outcome in MM transplanted patients.

PMID- 10942249
TI  - Spotlight on apoptosis. Introduction.

PMID- 10942250
TI  - Cell death beyond apoptosis.
AB  - Though the term apoptosis was originated in pathology and developmental biology
      as an alternative to necrosis, the tissue necrosis with inflammation is
      irrelevant to cell culture conditions where apoptosis is mostly studied.
      Furthermore, no one single morphological feature is either necessary or
      sufficient to define apoptosis. The emerging biochemical definition, a cell death
      with caspase activation, allows the distinction of alternative forms of cell
      death. Thus, inhibition of caspases delays but does not prevent cell death. Slow
      cell death without caspase activation may nevertheless be associated with DNA
      fragmentation. Oncogenic Ras, Raf, and mitogen-activated kinases inhibit
      apoptosis by affecting the cytochrome C/caspase-9 pathway but may arrest growth
      and cause slow cell death with delayed DNA fragmentation. Such 'slow' cell death
      without caspase activation is often caused by chemotherapeutic drugs. Whether a
      cell will undergo apoptosis or slow death depends not only on a chemotherapeutic
      agent but also on the readiness of cellular caspases. Therefore, one can
      distinguish apoptosis-prone (eg leukemia) vs apoptosis-resistant cells. Cell
      susceptibilities to spontaneous, starvation-induced and drug-induced apoptosis
      are correlated and characterize an apoptosis-prone phenotype. Finally,
      distinction of slow cell death allows rephrasing of a question regarding the goal
      of cancer therapy: apoptosis vs slow cell death, or cancer cell-selectivity
      regardless of the mode of cell death.

PMID- 10942251
TI  - Death and decoy receptors and p53-mediated apoptosis.
AB  - Recently, several tumor necrosis factor receptor 1 (TNF-R1) and Fas-related death
      receptors have been discovered and include DR3, DR4, DR5 and DR6. These receptors
      contain an extracellular region containing varying numbers of cysteine-rich
      domains and an intracellular region that contains the death domain. The death
      receptors are activated in a ligand-dependent or independent manner and transduce
      apoptotic signals via their respective intracellular death domains. In addition
      to death receptors, several decoy molecules have also been identified and include
      DcR1/TRID, DcR2/TRUNDD, DcR3 and osteoprotegrin (OPG). The decoy molecules do not
      transduce apoptotic signals but rather compete with the death receptors for
      ligand binding and thereby inhibit ligand-induced apoptosis. Recent evidence
      suggests that p53 upregulates the expression of death receptors Fas and DR5, and
      thus, may mediate apoptosis in part via Fas and/or DR5. However, p53 also
      regulates the expression of TRAIL decoy receptors DcR1/TRID and DR2/TRUNDD.
      Although the significance of p53-dependent regulation of decoy receptors remains
      unclear, evidence suggests that DcR1/TRUNDD appears to inhibit 53-mediated
      apoptosis. It is, therefore, possible that p53 may blunt its DR5-dependent
      apoptotic effects by controlling the levels of decoy receptors.

PMID- 10942252
TI  - The most unkindest cut of all: on the multiple roles of mammalian caspases.
AB  - The caspases, first discovered almost a decade ago, are intracellular cysteine
      proteases which have been shown to play an essential role in the initiation and
      execution phases of apoptotic cell death. Numerous strategies for the activation
      and inhibition of these 'killer' proteases have evolved, including the regulation
      of caspase expression and function at the transcriptional and post-translational
      level, as well as the expression of viral and cellular inhibitors of caspases.
      Emerging evidence in recent years has also implicated the caspases in various,
      nonapoptotic aspects of cellular physiology, such as cytokine processing during
      inflammation, differentiation of progenitor cells during erythropoiesis and lens
      fiber development, and proliferation of T lymphocytes, thus attesting to the
      pleiotropic functions of these proteases. The present review aims to discuss the
      multiple roles of the mammalian caspases with particular emphasis on their
      activation and regulation in cells of leukemic origin and the attendant
      possibilities of therapeutic intervention.

PMID- 10942254
TI  - The common deletion 657del5 in the Nibrin gene is not a major risk factor for B
      or T cell non-Hodgkin lymphoma in a pediatric population.

PMID- 10942253
TI  - Quantitative analysis of TEL/AML1 fusion transcripts by real-time RT-PCR assay in
      childhood acute lymphoblastic leukemia.

PMID- 10942255
TI  - Overexpression of heat shock protein 60 and the survival of blast in acute
      myeloid leukemia after induction therapy.

PMID- 10942256
TI  - Quantitation of PML-RARalpha transcripts in APL patients.

PMID- 10942257
TI  - On the acceptance of new experimental findings in science: is replication the
      key.

PMID- 10942258
TI  - Responses of the circadian system of rats to conditioned and unconditioned
      stimuli.
AB  - The circadian systems of rodents respond to light pulses presented during the
      subjective night with phase shifts and altered cellular activity in the
      suprachiasmatic nuclei (SCN), including expression of immediate-early genes
      (IEGs) such as c-fos. A recent study showed that a nonphotic stimulus (an air
      disturbance generated by a fan) that does not normally induce the expression of c
      fos-like immunoreactivity in the SCN of rats can be made to do so after being
      paired repeatedly with a light pulse in a Pavlovian conditioning paradigm.
      Furthermore, after conditioning (but not after noncontingent exposure to these
      stimuli), the fan also induced phase shifts in activity and body temperature
      rhythms comparable to those produced by light. The authors performed three
      experiments designed to replicate and extend these findings in rats. In
      experiment 1, rats were tested for conditioning effects of repeated pairings of a
      light pulse with a neutral air disturbance under a full photoperiod. In
      experiment 2, a modified conditioning paradigm was used in which a skeleton
      photoperiod served as both the entraining zeitgeber and the unconditioned
      stimulus. Animals in the paired and unpaired training conditions were exposed to
      both the light pulse and the air disturbance, but the air disturbance signaled
      the onset of light in the paired condition only. Phase shifts of wheel-running
      activity rhythms and gene expression in the SCN, intergeniculate leaflet, and
      paraventricular nucleus of the thalamus were assessed in animals following either
      of the training conditions or the control procedures. Experiment 3 assessed
      whether the air disturbance could entrain the circadian activity rhythms of rats
      with or without previous pairing with light in a classical conditioning paradigm.
      No evidence for classical conditioning, nor for unconditioned effects of the air
      disturbance on the circadian system, was found in these studies.

PMID- 10942259
TI  - Conditioned stimulus control in the circadian system: two tales tell one story.

PMID- 10942260
TI  - Learning and circadian behavior.

PMID- 10942261
TI  - Effects of the 5HT1A agonist/antagonist BMY 7378 on light-induced phase advances
      in hamster circadian activity rhythms during aging.
AB  - The entrainment of some circadian rhythms in rodents and humans to the
      environmental light-dark cycle deteriorates during aging. Recent evidence
      suggests that the time-keeping ability of the circadian pacemaker maintains its
      endogenous period in both hamsters and humans. This suggests that any changes in
      the coupling between environmental cues and the circadian pacemaker are not due
      to changes in "clock speed," but rather due to a weakened coupling between the
      afferent systems relaying environmental information and the circadian pacemaker
      located in the suprachiasmatic nucleus. The suprachiasmatic nucleus receives
      serotonergic input from the raphe nuclei, and serotonergic 5HT1A,7 agonists have
      been reported to lose their circadian phase-adjusting efficacy during aging in
      hamsters. In the present study, the authors report the effects of a novel
      serotonergic agonist BMY 7378 on light-induced phase advances during aging in the
      hamster. The present report demonstrates that BMY 7378 is a highly efficacious
      chronobiotic that more than doubles the magnitude of light-induced phase shifts
      in hamster wheel-running activity rhythms. Light-induced phase advances in
      hamster wheel-running activity of at least 6 h following a single systemic dose
      of BMY 7378 are routinely observed. Furthermore, BMY 7378 potentiation of phase
      shifts is maintained in old hamsters, suggesting that BMY 7378 has a different
      site of activity than previously reported 5HT1A,7 agonists that have a diminished
      effect on circadian phase during aging.

PMID- 10942262
TI  - Photoperiod and temperature interact to affect the GnRH neuronal system of male
      prairie voles (Microtus ochrogaster).
AB  - Individuals of numerous species limit energy expenditure during winter by
      inhibiting reproduction and other nonessential functions. To time these
      adaptations appropriately with the annual cycle, animals rely on environmental
      cues that predict, well in advance, the onset of winter. The most commonly
      studied environmental factor that animals use to time reproduction is
      photoperiod. Rodents housed in short photoperiods in the laboratory or in
      naturally declining day lengths exhibit pronounced alterations in reproductive
      function concomitant with alterations in the hypothalamic gonadotropin-releasing
      hormone neuronal system. Because animals in their natural environment use factors
      in addition to photoperiod to time reproduction, the present study sought to
      determine the independent effects of photoperiod and temperature, as well as the
      interaction between these factors, on reproductive parameters and the GnRH
      neuronal system. Male prairie voles were housed in either long (LD 16:8) or short
      (LD 8:16) day lengths for 10 weeks. Animals in each photoperiod were further
      subdivided into groups housed in either mild (i.e., 20 degrees C) or low (i.e., 8
      degrees C) temperatures. As shown with immunohistochemistry, voles that underwent
      gonadal regression in response to short photoperiods and long-day voles housed in
      low temperatures (and maintained large gonads) exhibit higher GnRH-immunoreactive
      (GnRH-ir) neuron numbers in the preoptic area/anterior hypothalamus (POA/AH)
      relative to all other groups. In addition, voles that underwent gonadal
      regression in response to both short days and low temperatures did not exhibit an
      increase in GnRH-ir neuron numbers compared to long-day, mild-temperature
      controls. These data suggest that photoperiod and temperature interact to
      influence reproductive function potentially by alterations of the GnRH neuronal
      system.

PMID- 10942263
TI  - Circadian regulation of visually evoked potentials in the domestic pigeon,
      Columba livia.
AB  - The avian circadian and visual systems are integrally related and together
      influence many aspects of birds' behavior and physiology. Certainly, light cycles
      and their visual perception are the major zeitgebers for circadian rhythms, but
      do circadian rhythms affect vision? To assess whether visual function is
      regulated on a circadian basis, flash-evoked electroretinograms (ERGs) and vision
      evoked potentials (VEPs) from the optic tectum (TeO) were recorded simultaneously
      in domestic pigeons at different circadian phases in a light-dark regime (LD) and
      in constant darkness (DD), while feeding activity was measured to determine
      circadian phase. In both LD and DD, the amplitudes of ERG b-waves were higher
      during the day than at night and latencies of a- and b-waves were longer at
      night. The median effective intensity for ERG a-wave was marginally higher during
      the day than during the night, indicating greater sensitivity at night, but this
      rhythm did not persist in DD. The amplitudes of TeO VEPs were also greater during
      the day, and latencies were greater at night in LD and DD. Together, the data
      indicate that a circadian clock regulates pigeon visual function at several
      integrative levels.

PMID- 10942264
TI  - Circadian thermoregulation in suckling rabbit pups.
AB  - The rabbit pup is well suited to track the age-dependent development of periodic
      thermoregulation during the suckling period. Since the litters are regularly
      nursed once per day for a total of 3 to 4 min, an exogenous, metabolic, nonphotic
      periodic variable is supposed to have an impact on the 24-h rhythm of body
      temperature. The authors monitored the course of core body temperature during the
      suckling period of 20 pups by means of a transmitter implanted intraperitoneally
      on day 3 postpartum. The 24-h mean rose from an average of 37.8+/-0.3 degrees C
      on day 4 of life to 39.5+/-0.2 degrees C at weaning on day 27, for 2 out of 20
      pups, and day 28, for 18 out of 20 pups. In constant dim illumination, the pups
      exhibited a 24-h rhythm even on postnatal day 4, which consolidated around days 5
      to 7. The rhythm consisted of a significant anticipatory rise of 0.4 to 0.6
      degrees C above the respective 24-h mean commencing 2.5 to 3.5 h prior to
      nursing. Milk intake was followed by a further increase of temperature for an
      additional 0.3 to 0.6 degrees C. Then the temperature dropped for 1.2 to 1.5
      degrees C within 1 to 3 h and returned to average 3 to 5 h later. During a 48-h
      fast, the rhythm continued to exist, though in a modified shape: the anticipatory
      component persisted almost unchanged; a further elevation of temperature,
      however, did not occur. Thus, the anticipatory component apparently is generated
      endogenously and the second surge represents an exogenous suckling-induced,
      thermogenic peak. When maternal nursing was advanced for 15 min/day for a total
      of 5 h, the temperature rhythm of the pups followed the shift of the zeitgeber in
      parallel. These data confirm the assumption that a circadian rhythm exists during
      the first postnatal days of the rabbit and that this rhythm is entrained by the
      24-h nursing rhythm. The authors suggest that the biological significance of a
      feeding entrainable oscillator (FEO) in the rabbit might be to activate the pups
      prior to the periodic nursing visit of the rabbit doe. Thus, the pups are
      prepared to quantitatively use the one and only short nursing episode per day for
      maximal milk ingestion.

PMID- 10942265
TI  - Temperature-independence of circannual variations in circadian rhythms of golden
      mantled ground squirrels.
AB  - In golden-mantled ground squirrels, phase angles of entrainment of circadian
      locomotor activity to a fixed light-dark cycle differ markedly between subjective
      summer and winter. A change in ambient temperature affects entrainment only
      during subjective winter when it also produces pronounced effects on body
      temperature (Tb). It was previously proposed that variations in Tb are causally
      related to the circannual rhythm in circadian entrainment. To test this
      hypothesis, wheel-running activity and Tb were monitored for 12 to 14 months in
      castrated male ground squirrels housed in a 14:10 LD photocycle at 21 degrees C.
      Animals were treated with testosterone implants that eliminated hibernation and
      prevented the marked winter decline in Tb; these squirrels manifested circannual
      changes in circadian entrainment indistinguishable from those of untreated
      animals. Both groups exhibited pronounced changes in phase angle and alpha of
      circadian wheel-running and Tb rhythms. Seasonal variation in Tb is not necessary
      for circannual changes in circadian organization of golden-mantled ground
      squirrels.

PMID- 10942266
TI  - Seasonal variation of depression and other moods: a longitudinal approach.
AB  - The present study examined the effect of season of the year on depression and
      other moods. Previous work, primarily cross sectional or retrospective in design
      and involving clinically depressed or seasonally affective disordered samples,
      has suggested that mood changes as a function of season. However, the literature
      also shows conflicting and/or inconsistent findings about the extent and nature
      of this relationship. Importantly, these prior studies have not adequately
      answered the question of whether there is a seasonal effect in nondepressed
      people. The present study employed a longitudinal design and a large sample drawn
      from a normal population. The results, based on those participants for whom mood
      measures were collected in each season, demonstrated strong seasonal effects.
      Beck Depression Inventory (BDI) scores were highest in winter and lowest in
      summer. Ratings on scales of hostility, anger, irritability, and anxiety also
      showed very strong seasonal effects. Further analyses revealed that seasonal
      variation in BDI scores differed for females and males. Females had higher BDI
      scores that showed strong seasonal variation, whereas males had lower BDI scores
      that did not vary significantly across season of the year.

PMID- 10942267
TI  - Effect of biological suspensions on the position of the binodal curve in aqueous
      two-phase systems.
AB  - This study is concerned with the influence of biological suspension on the
      position of the binodal curve in aqueous two-phase systems (ATPSs). Three
      different biological suspensions (i.e., disrupted yeast, E. coli homogenate and
      fermentation broth from Trichoderma harzianum) were selected and their impact
      upon ATPS performance was evaluated on the basis of changing volume ratio (Vr)
      and the position of the binodal curve of biological ATPSs (added with biomass).
      Biological ATPSs with initial Vr greater than 1 and long (>40%, w/w) tie-line
      length (TLL), exhibited significant changes in Vr when compared with that from
      non-biological systems. Such behaviour was associated with the top phase biomass
      accumulation. It was shown that the addition of the biological suspensions used
      in this study to ATPSs caused the binodal curve to displace towards the origin,
      which was associated with the critical contribution of the bio-polymer (present
      in the systems) to the phase formation. The practical implementation of ATPSs for
      the purification of biological materials exploiting the information reported in
      this study is discussed.

PMID- 10942268
TI  - Model process for separation based on unfolding and refolding of chymotrypsin
      inhibitor 2 in thermoseparating polymer two-phase systems.
AB  - For the design of a new separation process based on unfolding and refolding of
      protein, the partitioning behaviour of proteins was studied in thermoseparating
      polymer two-phase systems with varying pH and temperature. Chymotrypsin inhibitor
      2 (CI2), which unfolds reversibly in a simple two-state manner, was partitioned
      in an aqueous two-phase system (ATPS) composed of a random copolymer of ethylene
      oxide and propylene oxide (Breox) and dextran T-500. Between 25 and 50 degrees C,
      the partition coefficients of CI2 in Breox-dextran T-500 systems remain constant
      at neutral pH. However, there is a drastic increase at pH values below 1.7, 2.1,
      and 2.7 at 25, 40 and 50 degrees C, respectively. The partitioning behavior of
      CI2 was also investigated in thermoseparating water-Breox systems at 55-60
      degrees C, where CI2 was partitioned to the polymer-rich phase at pH values below
      2.4. These results on the CI2 partitioning can be explained by the conformational
      difference between the folded and the unfolded states of the protein, where the
      unfolded CI2 with a more hydrophobic surface is partitioned to the relatively
      hydrophobic Breox phase in both systems. A separation process is presented based
      on the partitioning behavior of unfolded and refolded CI2 by control of pH and
      temperature in thermoseparating polymer two-phase systems. The target protein can
      be recovered through (i) selective separation in Breox-dextran systems, (ii)
      refolding in Breox phase, and (iii) thermoseparation of primary Breox phase.

PMID- 10942270
TI  - Analysis of compression of polymer mushrooms using self-consistent field theory.
AB  - A number of new technologies, including new-generation biomaterials and
      chromatography resins, are based on passivation and modification of surfaces by
      terminally attaching polymer chains to the surface. However, little is known
      about these systems at the molecular level. In this work the compression of a
      single end-grafted polymer chain (or mushroom) by a disc of finite radius was
      investigated using a self-consistent field (SCF) lattice model. In accordance
      with results predicted using scaling theory [Subramanian et al., Europhys. Lett.
      29 (1995) 285 and Macromolecules 29 (1996) 4045], the compressed chain undergoes
      a smooth escape transition. However, under the assumption of angular symmetry, a
      first-order escape transition of the end-grafted chain is not observed,
      suggesting that the formation of a tether is required for the predicted phase
      transition. Segment density distributions and compression energies are calculated
      in a cylindrical lattice. The energy required to compress a chain increases
      monotonically as the disc is moved closer to the surface and becomes independent
      of chain length at strong compressions where the work of compression involves
      only confinement of the tether joining the escaped chain fraction to the grafting
      point.

PMID- 10942269
TI  - Investigation of mathematical methods for efficient optimisation of aqueous two
      phase extraction.
AB  - Mathematical strategies were applied to optimise the extraction of recombinant
      leucine dehydrogenase from E. coli homogenates and endoglucanase 1 from culture
      filtrates of Trichoderma reesei in polyethylene glycol-phosphate systems. The
      goal was to test mathematical tools which could facilitate the optimisation
      procedure in aqueous two-phase systems. A modified simplex approach, the method
      of steepest ascent and a genetic algorithm were successfully applied and
      compared. The methods differ in the height of the optimum found, the number of
      experiments and the time required. The genetic algorithm proved to be an
      optimisation procedure which can be used well in aqueous two-phase systems. The
      simplex procedure has to be further improved.

PMID- 10942271
TI  - Analysis of brush-particle interactions using self-consistent-field theory.
AB  - Non-specific protein adsorption can be reduced by attaching polymer chains by one
      end to a sorbent surface. End-grafted polymer modified surfaces have also found
      application in size-based chromatographic bioseparations. To better understand
      how to tailor surfaces for these applications, a numerical SCF model has been
      used to calculate theoretical results for the polymer density distribution of
      interacting polymer chains around a solute particle positioned at a fixed
      distance from a surface. In addition, the excess energy required to move the
      particle into the polymer chains (interaction energy) is calculated using a
      statistical mechanical treatment of the lattice model. The effect of system
      variables such as particle size, chain length, surface density and Flory
      interaction parameters on density distributions and interaction energies is also
      studied. Calculations for the interaction of a solute particle with a surface
      covered by many polymer chains (a brush) show that the polymer segments will fill
      in behind the particle quite rapidly as it moves toward the surface. When there
      is no strong energetic attraction between the polymer and solute we predict that
      the interaction energy will be purely repulsive upon compression due to losses in
      conformational entropy of the polymer chains. Above a critical chain length,
      which depends upon particle size, a maximum in the force required to move the
      particle toward the surface is observed due to an engulfment of the particle as
      chains attempt to access the free volume behind the particle. If an attraction
      exists between the polymer and solute, such that a minimum in the interaction
      energy is seen, the optimum conditions for solute repulsion occur at the highest
      surface density attainable. Long chain length can lead to increased solute
      concentration within the polymer layer due to the fact that an increased number
      of favourable polymer-solute contacts are able to occur than with short chains at
      a similar entropic penalty.

PMID- 10942273
TI  - Surfactant aggregates (solloids) adsorbed on silica as stationary chromatographic
      phases: structures and properties.
AB  - The structure and physical properties of solloids (surfactant aggregates adsorbed
      on surfaces) adsorbed on particles are of general interest. The relationship
      between solloid structure and properties of hexadecyltrimethylammonium bromide
      (HTAB), cetylpyridinium chloride (CPC) and cetylpyridinium salicylate (CPS)
      adsorbed on silica particles was studied by electron paramagnetic resonance (EPR)
      spectroscopy using the spin-probes peroxylaminedisulfonate (PADS) and 4-[N,N
      dimethyl-N-(n-hexadecyl)ammonium]-2,2,6,6-tetramethylpiperidin yl-N-oxy bromide
      (HTAB*). Using HTAB* incorporated in HTAB, CPC and CPC solloids and comparing the
      results to those in micelles, it was determined that for silica around pH 4 the
      solloids are very similar in properties to the micelles. This is consistent with
      a linear solvation-energy relationship (LSER) analysis of solute equilibration
      data which indicates that at pH 5 HTAB solloids have similar properties to HTAB
      micelles. The PADS spin-probe appears to be more sensitive to changes in the
      properties of the double layer, and substantial differences were observed between
      HTAB, CPC and CPS and as a function of HTAB concentration for HTAB solloids on
      silica.

PMID- 10942272
TI  - Model for the partition of metal ions in aqueous two-phase systems.
AB  - A model for the partition of metal ions in aqueous two-phase systems (ATPS) has
      been developed. The partition coefficient of a metal ion D(M), is a function of
      several variables of the ion (size, charge and electronegativity),
      characteristics of the ATPS such as type of salt, salt concentration and PEG
      concentration and additional inorganic salt present in the ATPS. The model has
      been tested for complex anions of BiX4- (BiCl4-, BiBr4- and BiI4-) and cations
      from groups I and II (Na+, Cs+, Ca2+, Sr2+ and Ba2+) giving a good correlation in
      both systems. It was found that for these systems partition coefficient increases
      with ion size and the variables Y which is a characteristic of the ATPS and Z
      which is a characteristic of the additional salt present in the system. The
      partition coefficient of BiX4- increases with the variable X which is a
      characteristic of the electrical interactions of the metal ion. The cations from
      groups II and I exhibit the opposite behavior, which is attributable to the ion
      charge.

PMID- 10942274
TI  - New aqueous two-phase system based on cashew-nut tree gum and poly(ethylene
      glycol).
AB  - The characterisation of a new system based on cashew-nut tree gum, a branched
      acidic heteropolysaccharide found in Brazil, and poly(ethylene glycol) (PEG) was
      studied. Phase diagrams are provided for the PEG-cashew-nut tree gum system. The
      influence of PEG molecular mass, tie-line length and pH on bovine serum albumin
      (BSA) partition was investigated. Protein partition coefficient was little
      influenced by changing PEG molecular mass. Increasing the tie-line length
      decreased the partition. Increasing the pH also raised the BSA partition
      coefficient. It is shown that systems formed by PEG and cashew-nut tree gum may
      be considered as an interesting alternative for use in protein purification.

PMID- 10942275
TI  - Stimuli-responsive separation of proteins using immobilized liposome
      chromatography.
AB  - The possibility of the stimuli-responsive separation of proteins was investigated
      using immobilized liposome chromatography (ILC) as novel aqueous two-phase
      systems. The specific capacity factor (k(s)) of beta-galactosidase, obtained by
      analysis of ILC, was varied by changing the pH of the solution and was maximized
      at the specific pH of 5 (k(s),max = 5.57). The k(s) values were found to
      correspond well with their local hydrophobicities, which can be determined by the
      aqueous two-phase partitioning method. The variation of k(s), therefore,
      indicates a change in the surface properties of a protein during conformational
      change under pH stimuli. A similar phenomenon is observed in the case of other
      proteins (alpha-glucosidase, k(s),max = 11.3 at pH 4; carbonic anhydrase from
      bovine, k(s),max = 6.53 at pH 4). The difference in the height and/or the
      position of the peaks of the ks-pH curves of each protein suggests a difference
      in their pH denaturation in the ILC column. Based on these results, the mutual
      separation of the above proteins at pH 4 could be successfully performed by
      selecting their specific capacity factor as a design parameter.

PMID- 10942276
TI  - Immobilized liposome chromatography for refolding and purification of protein.
AB  - Small unilamellar liposomes were utilized as a kind of aqueous two-phase system
      and artificial chaperone which specifically recognize protein conformation with
      fluctuated structure. Liposomes showed highly selective binding ability to
      conformationally changed proteins treated with various concentrations of
      guanidinium hydrochloride, as evaluated by immobilized liposome chromatography
      (ILC). In refolding of proteins, liposomes bound to refolding intermediate of
      proteins and prevented them from forming intermolecular aggregates. Refolding of
      bovine carbonic anhydrase, lysozyme and ribonuclease A was significantly improved
      in the presence of liposomes. Furthermore, by utilizing ILC, refolding of
      proteins was also successfully and simply carried out with considerable high
      reactivation yield.

PMID- 10942277
TI  - Drowning-out crystallisation of sodium sulphate using aqueous two-phase systems.
AB  - A novel method to obtain crystals of pure, anhydrous salt, using aqueous two
      phase systems was studied. A concentrated salt solution is mixed with
      polyethylene glycol (PEG), upon which three phases are formed: salt crystals, a
      PEG-rich liquid and a salt-rich liquid. After removal of the solid salt, a two
      phase system is obtained. Both liquid phases are recycled, allowing the design of
      a continuous process, which could be exploited industrially. The phase diagram of
      the system water-Na2SO4-PEG 3350 at 28 degrees C was used. Several process
      alternatives are proposed and their economic potential is discussed. The process
      steps needed to produce sodium sulphate crystals include mixing, crystallisation,
      settling and, optionally, evaporation of water. The yield of sodium sulphate
      increases dramatically if an evaporation step is used.

PMID- 10942278
TI  - Naphthol- and resorcinol-based azo dyes as metal ion complexants in aqueous
      biphasic systems.
AB  - Aqueous biphasic systems (ABS) are comprised of both a polymer-rich phase (e.g.,
      polyethylene glycol, PEG) and a salt-rich phase [e.g., (NH4)2SO4] such that both
      phases are 80% water on a molar basis. ABS have demonstrated applications as
      environmentally-friendly methods to separate relatively hydrophobic anionic
      species, such as pertechnetate and mercury halide anionic complexes, from high
      ionic strength solutions although partitioning of hydrated metal ions, such as
      Fe3+ and actinides, to the PEG-rich phase is negligible without the addition of a
      metal ion complexant to the system. Four naphthol- or resorcinol-based dyes; 1-(2
      pyridylazo)-2-naphthol (PAN), 1-(thiazolylazo)-2-naphthol (TAN), 4-(2-pyridylazo)
      resorcinol (PAR) and 4-(2-thiazolylazo)-resorcinol (TAR), each incorporating a
      naphthol or resorcinol with an ortho azo functional group, have been studied as
      metal ion extractants in ABS as a function of pH. In the PEG-2000/ (NH4)2SO4 ABS,
      the distribution ratios of Fe3+, Co2+ and Ni2- were enhanced by several orders of
      magnitude at high pH in contrast to the behavior of Cs+, Cd2+ and Eu3+ whose
      partitioning behavior was largely unaffected by the presence of these extractants
      at any pH. The three extracted metal ions, Fe3+, Co2+ and Ni2+, could be stripped
      by contact with a fresh salt phase at low pH.

PMID- 10942279
TI  - Polymer recycling in aqueous two-phase extractions using thermoseparating
      ethylene oxide--propylene oxide copolymers.
AB  - This is a study on the recovery and recycling of copolymer in aqueous two-phase
      systems containing random copolymers of ethylene oxide (EO) and propylene oxide
      (PO). The random copolymers separate from water solution when heated above the
      lower critical solution temperature (LCST). The primary phase systems were
      composed of EOPO copolymer and hydroxypropyl or hydroxyethyl starch. After phase
      separation the upper EOPO phase was removed and subjected to temperature induced
      phase separation. Copolymers with different EO/PO compositions have been
      investigated, EO50P050 [50% EO and 50% PO (w/w)], EO30PO70 and EO20P080. The
      temperature required for thermoseparation decreases when the PO content of the
      copolymer is increased. The effect on the recovery of copolymer after addition of
      salts, a second polymer or protein was investigated. The added components
      increased the recovery of copolymer after thermoseparation, e.g., increased the
      amount copolymer separated from the water phase after thermoseparation. Recycling
      of copolymer and measurements of polymer concentrations in the primary top and
      bottom phases after repeated recycling steps was performed. The fluctuation in
      polymer concentration of the phases was very small after recycling up to four
      times. Partitioning of the proteins BSA and lysozyme was studied in primary phase
      systems after recycling of copolymer. The partition coefficients of total protein
      and lysozyme was not significantly changed during recycling of copolymer. More
      than 90% of the copolymer could be recovered in the thermoseparation step by
      optimising the temperature and time for thermoseparation. In repeated phase
      partitionings in EOPO-starch systems the EO50PO50 copolymer could be recovered to
      77% including losses in primary system and thermoseparation, which is equivalent
      to a total copolymer reuse of 4.3 times.

PMID- 10942280
TI  - Investigation of aqueous biphasic systems for the separation of lignins from
      cellulose in the paper pulping process.
AB  - In efforts to apply a polymer-based aqueous biphasic system (ABS) extraction to
      the paper pulping process, the study of the distribution of various lignin and
      cellulosic fractions in ABS and the effects of temperature on system composition
      and solute partitioning have been investigated. The partitioning of three lignin
      species (Indulin AT, Indulin C, and Reax 85A) have been studied in ABS prepared
      from stock solutions of 40% (w/w) poly(ethylene glycol) (PEG)-2000 and increasing
      concentrations of K2CO3, (NH4)2SO4, and NaOH. The partitioning of these lignins
      is affected by the free energy of hydration of the salt forming the ABS, the tie
      line length, and the dissociation of the sulfonic acid and hydroxyl groups of the
      distributed solutes. The partitioning of fibrous cellulose and diethylaminoethyl
      cellulose have been studied in 40% (w/w) PEG-2000-(NH4)2SO4 ABS. The hydrophilic
      nature of these species is important in terms of their phase preference when
      designing a polymer-based aqueous biphasic extraction process for use in a paper
      pulping process. Both cellulosic samples do not dissolve, but rather report to
      the salt-rich phase of an ABS. In both chemical pulping and Organosolv pulping,
      temperatures in excess of 120 degrees C are needed to solubilize the lignin from
      the cellulose fraction of wood. To study the effects of temperature on the phase
      diagram and solute partitioning, phthalic acid and NH499TcO4 (as system probes)
      have been partitioned in 40% (w/w) PEG-2000-(NH4)2SO4 ABS at known tie line
      lengths as a function of temperature. Temperature does not appear to affect the
      partitioning results beyond the expected increase in phase divergence as
      temperature is increased. The PEG-2000 polymer itself appears to be stable to
      chemical pulping conditions.

PMID- 10942281
TI  - Solvatochromic studies in polyethylene glycol--salt aqueous biphasic systems.
AB  - The polarities of the co-existing phases of a polyethylene glycol (PEG)-2000
      K3PO4 aqueous biphasic system (ABS) have been examined using Reichardt's
      carboxylated pyridinium-N-phenoxybetaine dye as a probe. Using this probe, the
      polarities of these phases have been compared to those of conventional solvent
      extraction systems and micellar systems using values obtained from the
      literature. In general, these extraction systems are comparable in polarity to
      rather polar solvents. Data on the free energy of transfer of solvents suggests
      that this may be due to the failure of the probe to account for the real polarity
      of the salt-rich phase compared to the polymer-rich phase. Examination of the
      monophasic region of these systems suggests that the reason for this is that the
      probe is partitioned to a discreet solvent domain dominated by PEG, even though
      phase separation of the solution is not observed. The use of linear free energy
      relationships for the characterization of ABS is briefly discussed.

PMID- 10942282
TI  - Diffusion of lysozyme in gels and liquids. A general approach for the
      determination of diffusion coefficients using holographic laser interferometry.
AB  - A study on diffusion measurements of the protein lysozyme in liquids and agarose
      gels, at different pH and ionic strengths, has been performed using holographic
      laser interferometry. The measurements showed that the diffusive flux was very
      dependent on pH and ionic strength when the protein was not at its isoelectric
      point or when the charge of the lysozyme molecules was not screened by ions in
      the solution. Evaluation of the experimental data with Fick's law, resulted in
      diffusion coefficients for lysozyme that are strongly dependent on pH and ionic
      strength. Evaluation of the experimental data using a more general transport
      model, based on chemical potential gradients instead of concentration gradients
      resulted in lysozyme diffusion coefficients that are independent of pH and ionic
      strength. The chemical potential was estimated by using the Poisson-Boltzmann
      equation.

PMID- 10942283
TI  - Partitioning and diffusion of large molecules in fibrous structures.
AB  - This paper consists of three parts. In the first part we present diffusion and
      partition coefficients of proteins in agarose that were measured with gel
      permeation chromatography. In the second part we present a partition model which
      includes the effects of solute concentration and of cosolutes. In the third part
      we modify and extend Ogston's diffusion equation to account for the effects of
      solute and fiber flexibility, solute concentration and cosolutes. We find good
      agreement between the proposed models and data from the literature.

PMID- 10942284
TI  - Viscosity prediction of polyethylene glycol-dextran-water solutions used in
      aqueous two-phase systems.
AB  - The dynamic viscosities of aqueous polyethylene glycol and dextran, and
      poly(ethylene glycol)-dextran-water solutions were measured at temperatures of
      30, 50 and 70 degrees C. The poly(ethylene glycol) having a relative molecular
      mass of 8000, and dextran samples with relative molecular masses of 37 500, 494
      000, and 2 000 000 were used. A one-parameter Grunberg-like equation proposed
      earlier by us was used for estimating the values of viscosity of poly(ethylene
      glycol)-dextran-water solutions. The disposable parameter a for this temperature
      range was calculated as 1.81 for PEG 8000-dextran 37 500-water solutions, as 2.36
      for PEG 8000-dextran 494 000-water solutions, and as 2.57 for PEG 8000-dextran 2
      000 000-water solutions. It was observed that the relative errors get larger as
      the relative molecular mass of the dextran increases but vary between 0.00 and
      9.37 in absolute value. In view of the results obtained here and before, we may
      claim that the proposed model works constantly well at different temperatures
      giving comparable values for the disposable parameter a.

PMID- 10942285
TI  - Relative hydrophobicity of organic compounds measured by partitioning in aqueous
      two-phase systems.
AB  - Partitioning of a variety of organic compounds, the majority of which represent
      therapeutic drugs, was examined in an aqueous dextran-polyethylene glycol (Dex
      PEG) two-phase system containing 0.15 M NaCl in 0.01 M sodium phosphate buffer at
      pH 7.3 and in an octanol-buffer (0.15 M NaCl in 0.01 M sodium phosphate buffer,
      pH 7.3) system. The possibility of introducing compounds to be partitioned in an
      aqueous two-phase system with dimethyl sulfoxide, and the effect of this solvent
      on the solute partitioning was explored. Relative hydrophobicity of the compounds
      was estimated and expressed in equivalent numbers of methylene units. Comparison
      of the results obtained for several subsets of compounds in the octanol-buffer
      and in aqueous Dex-PEG two-phase systems clearly demonstrates the advantage of
      aqueous two-phase partitioning for the hydrophobicity measurements over
      partitioning in octanol-buffer system.

PMID- 10942286
TI  - Kinetics of phase separation under different process and design parameters in
      aqueous two-phase systems.
AB  - A practical study is presented of the effect of height/diameter (H/D) ratio of
      settlers on the kinetics of phase separation in aqueous two-phase systems
      (ATPSs). Poly(ethylene glycol) (PEG) 1000-phosphate systems with the presence of
      undiluted and diluted whey and disrupted yeast were used in batch studies. The
      influence of the biological suspensions on the rate of phase separation was
      investigated. It was observed that, phase separation time is much faster when
      disrupted suspension was used. The addition of undiluted suspensions to ATPSs
      slowed the process of phase separation. When the batch settler with a large cross
      section area (H/D ratio less than one) was used, the phases separated much faster
      than in a settler with a H/D ratio greater than one. Conclusions are drawn
      concerning the characterisation of the process and design parameters involved in
      the phase separation for the design of appropriate equipment.

PMID- 10942287
TI  - Conformational transition and mass transfer in extraction of proteins by AOT-
      alcohol--isooctane reverse micellar systems.
AB  - We examined quantitatively the effect of alcohols on protein and reverse micellar
      structure. We used circular dichroism (CD) to compare the effects of various
      alcohols on the protein structure, and percolation phenomena to evaluate the
      effects of various alcohols on reverse micellar structure. Upon the addition of
      alcohols to the bulk aqueous phase, proteins were denatured significantly,
      depending on the alcohol species and concentration, suggesting that use of
      alcohol directly to the stripping solution is not effective in back-extraction
      processes of proteins. In the present study, a new method, a small amount of
      alcohol is added to the surfactant-organic solution to improve the back
      extraction behaviors of proteins. Practically, in the back-extraction process,
      the alcohols suppressing the cluster formation of reverse micelles (high value of
      beta1), remarkably improved the back-extraction behavior of proteins. In
      addition, the same alcohol molecules showed a positive effect on the rate and
      fraction of protein back-extraction. From a result of the CD measurement of the
      back-extracted proteins, it was known that the alcohols added to reverse micellar
      solution allowed the proteins to back-extract safely without causing structural
      changes. These results show that the values of beta(t), defined by the variation
      of percolation processes, and the back-extraction behaviors of proteins have a
      good relationship, suggesting that the back-extraction processes were controlled
      by the micellar-micellar and protein-micellar interactions.

PMID- 10942288
TI  - Protein refolding using stimuli-responsive polymer-modified aqueous two-phase
      systems.
AB  - The function of a stimuli-responsive polymer was studied for the utilization of
      protein unfolding and refolding in protein separation using aqueous two-phase
      systems (ATPS). Poly(ethylene glycol) (PEG) bound to a thermo-reactive
      hydrophobic head (poly(propylene oxide)-phenyl group (PPO-Ph group)) was used as
      the functional ligand to modify the PEG phase of the aqueous two-phase systems.
      Firstly, refolding of carbonic anhydrase from bovine (CAB) was examined in the
      presence of PPO-Ph-PEG at various temperatures. The refolding yield of CAB was
      strongly enhanced and aggregate formation was suppressed by addition of PPO-Ph
      PEG at a specific temperature (50-55 degrees C). The change in the local
      hydrophobicity of CAB and PPO-Ph-PEG was characterized using the aqueous two
      phase partitioning method and a hydrophobic fluorescent probe. The local
      hydrophobicity of CAB was maximized at 60 degrees C. The local hydrophobicity of
      PPO-Ph-PEO was also found to be increased above 45 degrees C. A simple model for
      CAB refolding, which includes (i) PPO-Ph-PEG complex formation and CAB in the
      intermediate state and (ii) refolding and release of native CAB from the PPO-Ph
      PEG surface, is suggested based on the evaluated surface hydrophobicity.

PMID- 10942289
TI  - Determination of the dissociation constant of valine from acetohydroxy acid
      synthase by equilibrium partition in an aqueous two-phase system.
AB  - An aqueous polyethylene glycol/salt two-phase system was used to estimate the
      dissociation constant, K(dis), of the Escherichia coli isoenzyme AHAS III
      regulatory subunit, ilvH protein, from the feedback inhibitor valine. The amounts
      of the bound and free radioactive valine in the system were determined. A
      Scatchard plot of the data revealed a 1:1 valine-protein binding ratio and K(dis)
      of 133+/-14 microM. The protein did not bind leucine, and the ilvH protein
      isolated from a valine resistant mutant showed no valine binding. This method is
      very simple, rapid and requires only a small amounts of protein compared to the
      presently used equilibrium dialysis method.

PMID- 10942290
TI  - Poly(ethylene glycol)-based aqueous biphasic systems: effect of temperature on
      phase equilibria and on partitioning of 1,10-phenanthroline-copper(II) sulphate
      complex.
AB  - Solvent extraction is a proven technology for the selective removal and recovery
      of metal ions from aqueous solutions: the use of aqueous biphase systems can be
      attractive for many separation processes. These systems have usually been used
      previously at temperatures around 25 degrees C; however it is possible that
      better separations may be achieved at other temperatures: phase diagrams have
      been determined for a polyethylene glycol (AMW 3350)-ammonium sulphate-water
      system over the temperature range 269-343 K and the effect of temperature on
      partitioning has been determined for 1,10-phenanthroline-copper(II) sulphate
      complex.

PMID- 10942291
TI  - Partitioning of whey proteins, bovine serum albumin and porcine insulin in
      aqueous two-phase systems.
AB  - Partitioning of the proteins from cheese whey, bovine serum albumin and porcine
      insulin were analysed using aqueous two-phase systems (ATPS) prepared with PEG
      phosphate, PEG-citrate and PEG-maltodextrin (MD). Proteins were quantified
      through one of the following methods: FPLC, Bradford and spectrophotometry at 280
      nm. Results showed that whey proteins partitioned unevenly on the phases of the
      systems used, with alpha-lactoalbumin (alpha-La) concentrated in the upper phase
      and beta-lactoglobulin (beta-Lg) in the lower. Albumin in PEG-MD systems
      concentrated in the MD-rich lower phase. Porcine insulin showed great affinity
      with the PEG-rich phase, its partition coefficient was always over 10 and
      increases with PEG molecular mass.

PMID- 10942292
TI  - Bioaffinity extraction of glucoamylase in aqueous two-phase systems using starch
      as free bioligand.
AB  - Aqueous two-phase systems with bioligands bound to the polymer, usually
      polyethylene glycol (PEG), have high selectivity. However, such kind of systems
      can be costly since some specific synthetic ligands are expensive, making them
      non-viable for bioaffinity extraction of low-cost proteins. The use of free
      bioligands is an alternative for decreasing the high cost of these systems. This
      work describes the use of starch as a free bioligand on the partition of
      glucoamylase in PEG 300-phosphate system. The results were separated into two
      parts. In the first part, analysis of the starch distribution between the phases
      showed one-sided distribution to the bottom phase. In the second part, filtered
      broth from submerged cultivation of Aspergillus awamori, containing glucoamylase
      and contaminants, was submitted to the extraction in the system with starch. In
      the system without starch, glucoamylase and contaminants are partitioned in the
      upper phase. Upon starch addition, the partition coefficient of glucoamylase was
      decreased nine-fold without altering the partition of contaminants. These results
      indicate the possibility of separation of enzymes with high-molecular-mass and
      hydrophilic substrates, like glucoamylase, cellulase and pullulanase, from their
      contaminants in a one-step extraction. Since systems made of low-molecular-mass
      PEG partitioned almost all of the proteins to the upper phase, the separation can
      be achieved by extraction of the target enzyme in the bottom phase, as in the
      case of the presented study.

PMID- 10942293
TI  - Study on heterogeneity of beta-glucosidase from Aspergillus species by using
      counter-current distribution.
AB  - beta-Glucosidase plays a key role in cellulose degradation by cleaving its
      cellobiose units to glucose. The heterogeneity of the enzyme has been studied
      earlier by isoelectric focusing and several isoforms were found in the culture
      filtrate of Trichoderma and Aspergillus species. An aqueous two-phase system is
      an alternative fractionation method in which proteins are separated according to
      their net charge and surface properties. A dextran 500-poly(ethylene glycol) 8000
      system was used to study the distribution of beta-glucosidase of different
      origins. To investigate the heterogeneity of enzymes 56- and 145-step thin-layer
      counter-current distributions were carried out. beta-Glucosidase produced by
      Aspergillus niger and Aspergillus carbonarius has been shown to consist of at
      least three isoenzymes by applying this method. The three forms of A. niger show
      the corresponding partition ratios with G values of 0.13, 0.22 and 0.31; and A.
      carbonarius 0.14, 0.22 and 0.36, respectively. However, the relative amount of
      these isoforms differs strongly between the two microorganisms.

PMID- 10942294
TI  - Bovine serum albumin partitioning in an aqueous two-phase system: effect of pH
      and sodium chloride concentration.
AB  - The partitioning of bovine serum albumin (BSA) in a polyethylene glycol 3350 (8%
      w/w)-dextran 37 500 (6% w/w)-0.05 M phosphate aqueous two-phase was investigated
      at different pHs, at varying concentrations of sodium chloride at 20 degrees C.
      The effect of NaCl concentration on the partition coefficient of BSA was studied
      for the PEG-dx systems with initial pH values of 4.2, 5.0, 7.0, 9.0, and 9.8. The
      NaCl concentrations in the phase systems with constant pH value were 0.06, 0.1,
      0.2, 0.3, and 0.34 M. It was observed that the BSA partition coefficient
      decreased at concentrations smaller than 0.2 M NaCl and increased at
      concentrations greater than 0.2 M NaCl for all systems with initial pHs of 4.2,
      5.0, 7.0, 9.0, and 9.8. It was also seen that the partition coefficient of BSA
      decreased as the pH of the aqueous two-phase systems increased at any NaCl salt
      concentration studied.

PMID- 10942295
TI  - Partitioning of bovine serum albumin in an aqueous two-phase system: optimization
      of partition coefficient.
AB  - Partitioning of proteins in aqueous two-phase systems has been shown to provide a
      powerful method for separating and purifying mixtures of biomolecules by
      extraction. There are many factors which influence the partition coefficient K,
      the ratio of biomolecule concentration in top phase to that in the bottom phase,
      in aqueous two-phase systems. In this work, the partition behavior of pure bovine
      serum albumin in aqueous two-phase systems was investigated in order to see the
      effects of changes in phase properties on the partition coefficient K. pH and
      concentration of NaCl salt were found to be the factors having influence on K.
      Optimal conditions of these factors were obtained using the Box-Wilson
      experimental design. The optimum value of K was found as 0.018 when NaCl
      concentration, and pH were 0.0195 M and 8.9, respectively, for a phase system
      composed of 8% (w/w) polyethylene glycol 3350-6% (w/w) dextran 37 500-0.05 M
      phosphate at 20 degrees C.

PMID- 10942296
TI  - Application of aqueous two-phase partition to the production of homogeneous
      preparations of fluorescently labelled human serum albumin.
AB  - The development of a traceable molecular probe was investigated for the
      monitoring of partition behaviour of biomolecules in aqueous two-phase systems.
      This work was based upon the selective labelling of the free thiol group of human
      serum albumin (i.e. Cys34) with the fluorophore N-(iodoacetylaminoethyl)-5
      naphthylamine-1-sulphonic acid. The preparation of homogeneously labelled protein
      required purification operations. A succession of five processes was successfully
      applied, comprising two size-exclusion chromatographic operations by gel
      filtration and a series of three appropriately manipulated aqueous two-phase
      systems comprising PEG 1450 and phosphate salt. Aqueous two-phase partitioning is
      herein presented as an alternative to difficult separation and could be applied
      for 'fine' purifications.

PMID- 10942297
TI  - Peptides partitioning in an aqueous dextran-polyethylene glycol two-phase system.
AB  - Partitioning of glycine, lysine and aspartic acid and their oligopeptides in an
      aqueous dextran-polyethylene glycol two-phase system containing 0.15 M NaCl in
      0.01 sodium phosphate buffer, pH 7.3 and 0.11 M sodium phosphate buffer, pH 7.3
      was examined. Relative hydrophobicity of the amino acid residues and peptide
      bonds was estimated and expressed in equivalent numbers of methylene units.
      Analysis of a series of reversed di- and tripeptides in terms of relative
      hydrophobicity showed that the additivity principle does hold for the
      hydrophobicity of short peptides. The relative hydrophobicity of peptides is
      affected by the ionic composition of aqueous media as well as by the type of
      amino acid residues forming peptide bonds in a given peptide sequence.

PMID- 10942298
TI  - Purification of acetohydroxy acid synthase by separation in an aqueous two-phase
      system.
AB  - Extraction in a polyethylene glycol (PEG)-phosphate aqueous two-phase system was
      considered as a primary step in purification of the acetohydroxy acid synthase
      III large catalytic subunit from an E. coli extract. Extraction optimization was
      achieved by varying the system parameters. Two systems with the following weight
      compositions were chosen for purification: PEG-2000 (16%)-phosphate (6%) and PEG
      4000 (14%)-phosphate (5.5%)-KCl (8%), both at pH 7.0 and 1 mg total protein per 1
      g system. Significant purification was achieved by a single extraction step with
      70% recovery of the enzyme. After an additional ion-exchange chromatography step,
      pure enzyme was obtained in a 50% overall yield.

PMID- 10942299
TI  - Purification of soybean peroxidase (Glycine max) by metal affinity partitioning
      in aqueous two-phase systems.
AB  - Combining two concepts in downstream processing, this work investigates the
      partitioning of a crude soybean peroxidase (Glycine max) in an aqueous two-phase
      system by metal affinity. A liquid-liquid extraction process using metal ligands
      was developed in two steps with the aim of purifying the enzyme peroxidase. PEG
      4000 was activated using thionyl chloride, covalently linked to iminodiacetic
      acid (IDA), and the specific metal ligand Cu2+ was attached to the PEG 4000-IDA.
      In the first step, the system was composed of 14% (w/w) PEG 4000-IDA-Cu2+ and 8%
      (w/w) Na2SO4, and the peroxidase partitioned mainly to the top phase (K = 24). In
      the second step, a system formed by 14% PEG 4000 and 10% phosphate was used to
      revert the value of the partition coefficient of peroxidase to the bottom salt
      rich phase (K = 0.05), thereby achieving a recovery of 64% of the purified
      enzyme.

PMID- 10942300
TI  - Partitioning of peptides and recombinant protein-peptide fusions in
      thermoseparating aqueous two-phase systems: effect of peptide primary structure.
AB  - Genetic engineering has been used for fusion of peptides, with different length
      and composition, on a protein to study the effect on partitioning in an aqueous
      two-phase system. The system was composed of dextran and the thermoseparating
      ethylene oxide-propylene oxide random copolymer, EO30P070. Peptides containing
      tryptophan, proline, arginine or aspartate residues were fused at the C-terminus
      of the recombinant protein ZZ-cutinase. The aim was to find effective tags for
      the lipolytic enzyme cutinase for large-scale extraction. The target protein and
      peptide tags were partitioned separately and then together in the fusion proteins
      in order to gain increased understanding of the influence of certain amino acid
      residues on the partitioning. The salt K2SO4 was used to reduce the charge
      dependent salt effects on partitioning and to evaluate the contribution to the
      partition coefficient from the hydrophobic-hydrophilic properties of the amino
      acid residues. The effect of Trp on peptide partitioning was independent of the
      difference in primary structure for (Trp)n, (Trp-Pro)n, (Ala-Trp-Trp-Pro)n and
      was only determined by the number of Trp. The effect of the charged residues, Arg
      and Asp, was dependent on the surrounding residues, i.e. if they were situated
      next to Trp or not. The partitioning behaviour observed for the peptides was
      qualitatively and in some cases also quantitatively the same as for the fusion
      proteins. The effect of the salts sodium perchlorate and triethylammonium
      phosphate on the partitioning was also studied. The salt effects observed for the
      peptides were qualitatively similar to the effects observed for the fusion
      proteins.

PMID- 10942302
TI  - Partitioning behavior of amino acids in aqueous two-phase systems with recyclable
      volatile salts.
AB  - As part of an ongoing research effort on aqueous two-phase systems (ATPSs) with
      volatile salts, this work describes the partitioning behavior of a series of
      amino acids, namely L-serine, glycine, L-alanine, L-valine, L-methionine, L
      isoleucine, and L-phenylalanine, in these systems. The results show that amino
      acids partition in a similar way in polymer-volatile salt ATPSs and in
      traditional polymer-salt ATPSs. Increasing amino acid hydrophobicities lead to
      increasing partition coefficients. Moreover, the common linear relationship
      between the logarithm of the partition coefficient and the tie line length is
      observed here as well. Furthermore, the relation between relative partition
      coefficients and relative hydrophobicities of amino acids in the extraction
      systems investigated in this work is comparable to that in other extraction
      systems.

PMID- 10942301
TI  - Affinity partitioning of a poly(histidine)-tagged integral membrane protein,
      cytochrome bo3 ubiquinol oxidase, in a detergent--polymer aqueous two-phase
      system containing metal-chelating polymer.
AB  - A system has been developed for selective partitioning of membrane proteins. For
      the first time, an integral membrane protein, cytochrome bo3 ubiquinol oxidase
      from Escherichia coli, has been affinity partitioned in an aqueous two-phase
      system. The systems used were different detergent/polymer aqueous two-phase
      systems containing a metal-chelating polymer, such as poly(ethyleneglycol)
      iminodiacetic acid-Cu(II) as well as dextran-iminodiacetic acid-Cu(II). Many non
      ionic detergents, such as alkyl(polyethyleneoxide) (CmEOn), Triton, Tween and
      alkylglucosides, form two-phase systems in mixture with polymers, such as dextran
      and poly(ethyleneglycol), i.e., a micelle-enriched phase in equilibrium with a
      polymer-enriched phase are formed. In general, membrane proteins partition
      strongly to the micelle phase. We show that it is possible to selectively
      partition a poly(histidine)-tagged integral membrane protein into the polymer
      phase by metal affinity partitioning, with a shift in the partitioning
      coefficient from 0.015 to 4.8 (300-fold). The affinity partitioning was
      characterized and the effects of ligand concentration, pH, time, salts, buffer
      type, imidazole and charged detergent are discussed. Thus, a fast and mild
      affinity procedure for the purification of integral membrane proteins can be
      developed in affinity detergent/polymer aqueous two-phase systems, and the method
      is especially suitable for the purification of labile integral membrane proteins,
      such as receptors.

PMID- 10942303
TI  - Phase behavior and protein partitioning in aqueous two-phase systems of cationic-
      anionic surfactant mixtures.
AB  - Cationic-anionic surfactant mixtures can form aqueous two-phase systems. Such
      aqueous surfactant two-phase systems (ASTP systems) can be used for separation
      and purification of biomaterials. In this work we investigated the phase behavior
      and the partitioning of BSA and lysozyme in the ASTP system formed by mixtures of
      dodecyltriethylammonium bromide and sodium dodecylsulfate (SDS). The pseudo
      ternary phase diagram of these mixtures at low total surfactant concentrations
      contains two narrow two-phase regions, which represent two kinds of different
      ASTP systems formed when cationic and anionic surfactants are in excess,
      respectively (called ASTP-C and ASTP-A). The phase separation is associative, one
      phase is surfactant-rich, and the other phase is surfactant-depleted. Mechanisms
      behind the phase behavior are discussed. The phase behavior, especially phase
      separation time and phase volume ratio, is strongly influenced by total
      concentration and molar ratio of mixed surfactants. The effect of molar ratio is
      strong, which enables one to get desired phase systems also at very low total
      concentration by tuning the molar ratio of the surfactants. It was shown that the
      marked differences of surfactant concentration between the phases makes proteins
      distribute with different partitioning coefficients. The charges on the micellar
      surface, which can be adjusted by tuning the molar ratio of cationic surfactants
      to anionic surfactants, enhance the selectivity of protein partitioning by
      electrostatic effects. At pH 7.1, in the ASTP-C systems, negatively charged BSA
      is concentrated in the surfactant-rich phase and positively charged lysozyme in
      the surfactant-depleted phase, while in ASTP-A systems, a totally opposite
      partitioning was observed. It was shown that lysozyme could retain activity in
      ASTP systems.

PMID- 10942304
TI  - Partitioning of xylanolitic complex from Penicillium janthinellum by an aqueous
      two-phase system.
AB  - This work evaluates the influences of five parameters (pH, PEG molecular mass,
      PEG concentration, concentration of buffer K2HPO4-KH2PO4 and NaCl concentration)
      on xylanolitic complex partitioning produced by P. janthinellum in aqueous two
      phase systems, using a 2(5) factorial experimental design. A mathematical model
      to quantify the influence of these parameters was attained and statistically
      tested. The optimum point for total protein extraction was obtained under the
      following conditions: pH 7.0, PEG 10 000, 3.67% PEG, 10% potassium phosphate and
      12.4% NaCl. The partition coefficient (K) value experimentally obtained was 5.25
      and that predicted by the model was 5.89.

PMID- 10942305
TI  - Extraction in aqueous two-phase systems of alkaline xylanase produced by Bacillus
      pumilus and its application in kraft pulp bleaching.
AB  - The aim of this work was to extract and to purify xylanase, produced by Bacillus
      pumilus from the crude fermentation broth, using aqueous two-phase systems
      (ATPS). The xylanase was extracted by partitioning in ATPS composed of phosphate
      and polyethylene glycol (PEG). The effect of tie-line length, PEG molecular mass
      and NaCl concentrations upon the purification factors and yields of xylanase were
      investigated by statistical design. The best system studied was that containing
      22% PEG6000, 10% K2HPO4 and 12% NaCl with a purification factor of 33 and a 98%
      yield of enzyme activity. This system was also used for continuous extraction in
      a pulsed caps column. Subsequently, the xylanase from the crude fermentation
      broth was tested in hardwood kraft pulp bleaching.

PMID- 10942306
TI  - Isoelectric precipitation of soybean protein using carbon dioxide as a volatile
      acid.
AB  - A novel process is presented for the isoelectric precipitation of soy protein,
      using carbon dioxide as a volatile acid. By contacting a soy meal extract with
      pressurized carbon dioxide, the solution pH was decreased to the isoelectric
      region of the soy proteins. Complete precipitation of the precipitable soy
      proteins could be achieved for protein concentrations up to 40 g/l at pressures
      less than 50 bar. Isoelectric precipitation with a volatile acid enabled accurate
      control of the solution pH by pressure and eliminated the local pH overshoot,
      usual in conventional precipitation techniques. The advantage of the improved
      precipitation control was reflected by the morphology of the precipitate
      particles. Protein aggregates formed by CO2 were perfectly spherical whereas
      protein precipitated by sulfuric acid had an irregular morphology. The influence
      of process variables to control particle size is discussed.

PMID- 10942307
TI  - Applications of aqueous two-phase partition to isolation of membranes from
      plants: a periodic NADH oxidase activity as a marker for right side-out plasma
      membrane vesicles.
AB  - Phase separations using standardized mixtures of polyethylene glycol, dextran and
      potassium phosphate are used widely to prepare highly purified plasma membranes
      from plants and in the preparation of chloroplast subfractions. Other uses
      include the removal of right side-out plasma membrane vesicles as contaminants
      from Golgi apparatus, endoplasmic reticulum and tonoplast (vacuole membrane)
      fractions and separation of right side-out and inside-out plasma membrane
      vesicles. The higher degree of separation between plasma membranes into the upper
      phase and internal membranes into the lower phase is in large measure due to the
      fact that only plasma membranes are oriented cytoplasmic side in. Most other
      membranes are oriented cytoplasmic side-out. This property extends to separations
      of right side-out and inside-out plasma membrane vesicles and to the separation
      of right side-out and inside-out sub-mitochondrial particles. The inside-out
      vesicles partition into the lower phase whereas the right side-out vesicles
      remain in the upper phase. The lack of efficacy of aqueous two-phase partitioning
      in other types of membrane separations is apparently due to the fact that surface
      characteristics that may distinguish different internal membranes are not located
      at the cytosolic membrane surface. At present there are no direct enzymatic
      markers for right side-out plasma membrane vesicles from plants. Demonstrations
      of sidedness and estimates of fraction purity are based on measurements of
      latency of marker enzymes, e.g., ATPases, at the cytosolic surface. This report
      describes a periodic NADH oxidase as an enzyme marker for right side-out plasma
      membrane vesicles not requiring detergent disruptions of vesicles for measurement
      of activity.

PMID- 10942308
TI  - Aqueous two-phase partition applied to the isolation of plasma membranes and
      Golgi apparatus from cultured mammalian cells.
AB  - Partitioning in dextran-poly(ethylene)glycol (PEG) aqueous-aqueous phase systems
      represents a mature technology with many applications to separations of cells and
      to the preparation of membranes from mammalian cells. Most applications to
      membrane isolation and purification have focused on plasma membranes, plasma
      membrane domains and separation of right side-out and inside-out plasma membrane
      vesicles. The method exploits a combination of membrane properties, including
      charge and hydrophobicity. Purification is based upon differential distributions
      of the constituents in a sample between the two principal compartments of the two
      phases (upper and lower) and at the interface. The order of affinity of animal
      cell membranes for the upper phase is: endoplasmic reticulum <mitochondria<Golgi
      apparatus<lysosomes and endosomes< plasma membranes. Salt concentrations and
      temperature affect partitioning behavior and must be precisely standardized. In
      some cases, it is more fortuitous to combine aqueous two-phase partition with
      other procedures to obtain a more highly purified preparation. A procedure is
      described for preparation of Golgi apparatus from transformed mammalian cells
      that combines aqueous two-phase partition and centrifugation. Also described is a
      periodic NADH oxidase, a new enzyme marker for right side-out plasma membrane
      vesicles not requiring detergent disruptions for measurement of activity.

PMID- 10942309
TI  - Affinity partitioning of biotinylated mixed liposomes: effect of charge on biotin
      -NeutrAvidin interaction.
AB  - The partitioning behaviour of biotinylated mixed liposomes in aqueous
      poly(ethylene glycol)/dextran two-phase systems containing NeutrAvidin-dextran
      suggests that the biotin-NeutrAvidin affinity interaction is charge dependent.
      Biotinylated phosphatidylcholine liposomes with a low negative surface charge
      distributed in the NeutrAvidin-containing bottom phase at neutral pH, but the
      introduction of additional negative charges by including phosphatidylserine or
      the surfactant sodium dodecylsulfate in the liposomes caused them to distribute
      in the poly(ethylene glycol)-rich top phase instead. By gradually lowering the pH
      of the affinity two-phase system below the isoelectric point (6.3) of
      NeutrAvidin, negatively charged phosphatidylserine/phosphatidylcholine liposomes
      increasingly were attracted by NeutrAvidin to the bottom phase. It is suggested
      that acidic amino acids present at the rim of the biotin-binding pocket of
      NeutrAvidin may interact electrostatically with charged residues of the closely
      apposed liposome surface affecting the affinity interaction.

PMID- 10942310
TI  - Purification of rabbit lacrimal gland plasma membranes by aqueous two-phase
      affinity partitioning.
AB  - We describe the purification of lacrimal gland plasma membranes by affinity
      partitioning using a two-phase system containing polyethylene glycol and dextran
      in which wheat germ agglutinin conjugated to dextran is used as affinity ligand.
      When partitioning a microsomal fraction, the plasma membrane marker 5'
      nucleotidase was obtained in the affinity ligand-containing bottom phase, whereas
      the endoplasmic reticulum marker NADH-ferricyanide reductase remained in the top
      phase. The affinity partitioning behaviour of components involved in exocytosis
      and cellular signalling was also examined.

PMID- 10942311
TI  - Aroma compounds recovery from mycelial cultures in aqueous two-phase processes.
AB  - This paper presents the evaluation of the potential use of aqueous two-phase
      systems (ATPS) for the recovery of 6-pentyl-alpha-pyrone (6PP) produced by
      Trichoderma harzianum. The partition behaviour of 6PP and Trichoderma harzianum
      mycelium (biomass) in polyethylene glycol (PEG)-salt (phosphate and sulphate) and
      PEG-dextran ATPS was investigated. The influence of defined system parameters
      (e.g. molecular mass of PEG and dextran, volume ratio, etc.) on the partition
      behaviour of 6PP and Trichoderma harzianum mycelium was evaluated to select under
      which conditions 6PP and mycelium partition to opposite phases. In PEG-dextran
      systems either large extraction phases were required or mycelium and 6PP
      partitioned to the same phase. ATPS comprising V(r)=0.23, PEG 8000 6.6% w/w and
      sulphate 14.0% w/w provided the best conditions to satisfy the process
      requirement of biomass accumulation into the bottom phase and 6PP concentration
      in the top phase.

PMID- 10942312
TI  - Recovery in aqueous two-phase systems of nanoparticulates applied as surrogate
      mimics for viral gene therapy vectors.
AB  - The partition behaviour of nanoparticulate inclusion bodies (IBs) in various
      states of purity were evaluated as surrogate mimics for adenovirus and retrovirus
      products in method scouting experiments with aqueous two-phase systems (ATPSs).
      Such systems are proposed for effective, high capacity downstream processing
      (DSP) of viral gene therapy vectors. Studies with mimics provided simple
      descriptions of particle partition which may benefit the field of vector DSP,
      where experimental material is rarely available for research and development in
      quantities and concentrations representative of clinical manufacture.
      Polyethylene glycol (PEG)-salt and PEG-dextran ATPSs were screened in respect of
      the partition recovery of IBs from crude feedstocks. Select candidate systems
      were similarly evaluated with limited preparations of adenovirus and retrovirus
      with respect to fractional recoveries of infectivity and particle number.
      Maintenance of the former was good, whilst comparison of the latter with
      quantitation of unwashed and washed IBs indicated poor utilisation of the
      inherent high capacities of ATPSs in viral experiments. This is discussed in the
      context of the volumetric throughput and capacities reported in the literature
      for the recovery of infective viruses in ultracentrifugation and chromatographic
      processes.

PMID- 10942313
TI  - Simultaneous accumulation of low-molecular-mass RNA at the interface along with
      accumulation of high-molecular-mass RNA on aqueous two-phase system partitioning.
AB  - On partitioning in the potassium phosphate-PEG aqueous two-phase system, the
      simultaneous accumulation of the low-molecular-mass RNA at the interface along
      with accumulation of the coexisting high-molecular-mass RNA was quantitatively
      shown. The low-molecular-mass RNA was inherently partitioned between the top and
      bottom phases if partitioned alone. However, the low-molecular-mass RNA was
      caught in the interface to a significant extent if partitioned with the
      coexisting high-molecular-mass RNA. The degree of the accumulation of low
      molecular-mass RNA increased with an increase in the content of the coexisting
      high-molecular-mass RNA, while the high-molecular-mass RNA was mostly accumulated
      at the interface.

PMID- 10942314
TI  - Cold cataracts: a naturally occurring aqueous two-phase system.
AB  - The cytoplasm of the eye lenses shows a liquid-liquid phase transition similar to
      the one observed in aqueous two-phase systems. This phenomenon is known as cold
      cataracts. We have studied the solution behavior of the main protein fractions
      that constitute the lenses' cytoplasm using small-angle neutron scattering and
      dynamic light scattering. Our results provide evidence that an intricate balance
      of forces underlines the physical phenomena responsible for the optical
      properties of the lenses and for the phase transition that is observed as the
      temperature is lowered below some critical value. These forces include solvent
      mediated forces besides the more conventional Coulombic and dispersion forces.
      This study suggests that solvent mediated forces must be included to successfully
      model liquid-liquid phase transitions like the ones observed in cold cataracts or
      in aqueous two-phase systems.

PMID- 10942315
TI  - Lowering of plasma LDL cholesterol in hamsters by the tomato glycoalkaloid
      tomatine.
AB  - Tomatoes contain the steroidal glycoalkaloid tomatine, which has been reported to
      form strong, insoluble complexes with cholesterol in vitro. To determine whether
      tomatine can reduce dietary cholesterol absorption and plasma levels of
      cholesterol and triglycerides, we fed hamsters a high-fat, high-cholesterol diet
      with 0.05-0.2% added tomatine in the diet. The tomatine diets induced lowering of
      serum low-density lipoprotein (LDL) without changing high-density lipoprotein
      (HDL) cholesterol. Compared to the control diets, four- to fivefold more labeled
      dietary cholesterol and coprostanol was excreted in the feces of the tomatine-fed
      hamsters. The amount of cholesterol excreted in the feces corresponded to the
      amount of tomatine in the diet. These observations suggest that due to the
      formation of an insoluble tomatine-cholesterol complex and its excretion in the
      feces, very little dietary tomatine is absorbed from the digestive tract into the
      blood stream. They are also consistent with the reported low oral toxicity of
      tomatine compared to other glycoalkaloids.

PMID- 10942316
TI  - Estrogenic activity of flavonoids in mice. The importance of estrogen receptor
      distribution, metabolism and bioavailability.
AB  - The in vivo estrogenic potential of the flavonoids apigenin, kaempferol,
      genistein and equol was investigated in immature female mice. Genistein and
      equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17-20,
      100 mg/kg body weight], was found to significantly increase uterine weights and
      the overall uterine concentration of estrogen receptor alpha (ERalpha). In
      kaempferol- and equol-exposed mice the cytosolic ERalpha concentration was
      significantly increased as compared to the solvent control, which is speculated
      to result in an increased sensitivity of the uterus to subsequently encountered
      estrogens. Oral administration of equol, genistein, biochanin A and daidzein to 6
      week-old female mice revealed a great variation in their systemic
      bioavailability. The urinary recovery of equol was thus over 90% of a single
      gavage administered dose, whereas the urinary recoveries of biochanin A,
      genistein and daidzein were 16, 11 and 3%, respectively. Most of the metabolites
      were either hydroxylated or dehydrogenated forms of the parent compounds. The in
      vitro estrogenic potency of some of the metabolites was greater than that of the
      parent compounds, whereas others were of similar or lower potency.
      Bioavailability, metabolism, the ability to alter ERalpha distribution in the
      uterus and the estrogenic potential of parent compound and metabolites may thus
      contribute to the differences in in vivo estrogenicity of dietary flavonoids.

PMID- 10942317
TI  - Interleukin-6-deficient mice refractory to IgA dysregulation but not anorexia
      induction by vomitoxin (deoxynivalenol) ingestion.
AB  - Dietary exposure to the trichothecene vomitoxin (VT) causes feed refusal and
      elevates IgA production in the mouse. Based on the observations that IL-6 can
      cause anorexia and promote IgA production and that gene expression of this
      cytokine is increased in vivo and ex vivo on VT exposure, we hypothesized that IL
      6 is an essential cytokine in VT-induced feed refusal and IgA dysregulation. To
      test this hypothesis, the effects of dietary VT on feed intake, weight gain,
      serum IgA levels and kidney mesangial IgA deposition in an IL-6-"knockout" mouse
      (B6129-IL6(tmi Kopf)) were compared to those in both a corresponding "wildtype"
      (B6129F2) and a previously characterized "sentinel" strain (B6C3F1) that possess
      the intact gene for this cytokine. IL-6 deficiency did not alter the capacity of
      VT to cause feed refusal or impair weight gain. VT-fed B6129F2 and B6C3F1 mice
      had significantly higher serum IgA concentrations than did their corresponding
      controls fed clean diet, whereas significant differences were not observed
      between IL-6 KO mice fed VT or control diets. Kidneys taken from VT-fed wild-type
      and sentinel mice had significantly increased mesangial IgA deposition as
      compared to controls. While slight increases in mesangial IgA were observed in VT
      fed IL-6 KO mice, mean fluorescence intensities were significantly less than that
      found in the corresponding wild-type and sentinel strains. IL-6 KO mice appeared
      to be less prone to the development of microscopic haematuria following VT
      exposure than were the corresponding wild-type and sentinel strains. In total,
      the results suggested that IL-6-deficient mice were refractory to VT-induced
      dysregulation of IgA production and development of IgA nephropathy, whereas
      chronic VT-mediated nutritional effects related to feed intake and weight gain
      were unaffected.

PMID- 10942318
TI  - Inhibition of gastric mucosal damage by methylglyoxal pretreatment in rats.
AB  - The effect of methylglyoxal pretreatment on gastric mucosal injuries caused by
      80% ethanol, 25% NaCl and 0.2 M NaOH, was investigated in rats. The effects
      caused by pylorous ligation accumulated gastric acid secretions and ethanol
      induced changes in gastric mucus secretions, levels of proteins, nucleic acid,
      malondialdehyde (MDA) and non-protein sulfhydryl groups were also investigated.
      Methylglyoxal pretreatment at oral doses of 50, 100 and 200 mg/kg body weight was
      found to provide a dose-dependent protection against the ulcerogenic effects of
      different necrotizing agents used. With the same dose regimen methylglyoxal
      offered significant protection against ethanol-induced damage on the parameters
      evaluated for histopathology. Furthermore, the pretreatment afforded a dose
      dependent inhibition of pylorous ligated accumulation of gastric acid secretions
      and ethanol-induced depletion of stomach wall mucus, proteins, nucleic acids, NP
      SH contents and an increase in the MDA levels in gastric tissue. The protective
      effect of methylglyoxal against ethanol-induced damage to the gastric wall mucosa
      may be mediated through its effect on mucous production, proteins, nucleic acids,
      NP-SH groups and its free-radical scavenging property under the influence of
      polyamines stimulated by ornithine decarboxylase activity (ODC).

PMID- 10942319
TI  - Effect of taurine on toxicity of oxidized fish oil in rats.
AB  - An attempt was made to study the effect of dietary taurine on the toxicity of
      oxidized fish oil in male Wistar rats. The rats were fed different diets with or
      without supplement of 5% taurine and 3% oxidized fish oil. After feeding diet
      with 3% oxidized fish oil and 5% taurine at the same time, taurine could improve
      the decrease of body weight and the glutathione (GSH) level in the liver, and the
      increase of relative ratios of liver and kidney weight to body weight and
      thiobarbituric acid-reactive substances (TBARS) level in the liver of rats caused
      by oxidized fish oil It also could reduce the activities of aspartate
      transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) in
      the plasma of rats caused by oxidized fish oil. It was also found that taurine
      possessed a good recovering effect and a short-term preventing effect from the
      toxicity of oxidized fish oil in rats. Judging from these data, this indicates
      that taurine may play an important role in reducing the toxic effect of oxidized
      fish oil in rats.

PMID- 10942320
TI  - Immunoaffinity column as clean-up tool for determination of trace amounts of
      microcystins in tap water.
AB  - Trace amounts of microcystins (MCs) in drinking water should be monitored because
      of their potential hazard for human health as an environmental tumor promoter. We
      describe here a new clean-up tool with immunoaffinity column (IAC) for
      determination of trace amounts of MCs (from pg to microg/litre) in tap water. The
      water samples were concentrated with IAC clean-up and MCs levels were determined
      by HPLC with UV detection or enzyme-linked immunosorbent assay (ELISA). In the
      combination with HPLC analysis, mean recovery of microcystin-LR (MCLR),-RR and-YR
      spiked to tap water were 91.8%, 77.3% and 86.4%, respectively, in the range 2.5
      100 microg/litre. The chromatogram of MCs-spiked tap water sample cleaned up with
      IAC showed effective elimination of the impurities compared to that with
      octadecyl silanized cartridge, which had been cleaned up with a conventional
      method. Also, in the combination with highly sensitive ELISA, mean recovery of
      MCLR spiked to tap water was 80% in the range 0.1-1000 ng/litre. The combined
      methods developed here can detect pg to microg/litre of MCs in tap water. The
      overall results indicated that IAC will be suitable as a clean-up tool for trace
      amounts of MCs in tap water.

PMID- 10942321
TI  - Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach
      cancer risk: results from analyses in the Netherlands Cohort Study.
AB  - Both carcinogenic and anticarcinogenic properties have been reported for the
      synthetic antioxidants butylated hydroxyanisole (BHA) and butylated
      hydroxytoluene (BHT). The association between dietary intake of BHA and BHT and
      stomach cancer risk was investigated in the Netherlands Cohort Study (NLCS) that
      started in 1986 among 120,852 men and women aged 55 to 69 years. A semi
      quantitative food frequency questionnaire was used to assess food consumption.
      Information on BHA or BHT content of cooking fats, oils, mayonnaise and other
      creamy salad dressings and dried soups was obtained by chemical analysis, a Dutch
      database of food additives (ALBA) and the Dutch Compendium of Foods and Diet
      Products. After 6.3 years of follow-up, complete data on BHA and BHT intake of
      192 incident stomach cancer cases and 2035 subcohort members were available for
      case-cohort analysis. Mean intake of BHA or BHT among subcohort members was 105
      and 351 microg/day, respectively. For consumption of mayonnaise and other creamy
      salad dressings with BHA or BHT no association with stomach cancer risk was
      observed. A statistically non-significant decrease in stomach cancer risk was
      observed with increasing BHA and BHT intake [rate ratio (RR) highest/lowest
      intake of BHA = 0.57 (95% confidence interval (CI): 0.25-1.30] and BHT = 0.74
      (95% CI: 0.38-1.43). In this study, no significant association with stomach
      cancer risk was found for usual intake of low levels of BHA and BHT.

PMID- 10942322
TI  - 13-week drinking water toxicity study of hydrogen peroxide with 6-week recovery
      period in catalase-deficient mice.
AB  - A GLP OECD guideline study was conducted to evaluate the subchronic toxicity of
      hydrogen peroxide (HP) when administered continuously in the drinking water of
      catalase-deficient (C57BL/6N) mice and reversibility of toxic effects. Groups of
      mice (15/sex/group) received solutions of 0, 100, 300, 1000 or 3000 ppm HP in
      distilled water for 13 weeks; five/sex/group continued on untreated distilled
      water for an additional 6 weeks. Animals drinking 3000 ppm HP exhibited depressed
      water and food consumption and body weight. Females drinking 1000 ppm HP had
      reduced water consumption with intermittent effects on food consumption, but no
      body weight effects. HP administration did not produce any mortality, clinical
      signs, hematological effects or organ weight effects on brain, liver, kidneys,
      adrenals, testes, heart or spleen. Total protein and globulin were depressed
      among high dose males. Mild to minimal duodenal mucosal hyperplasia was noted in
      animals receiving 1000 and 3000 ppm HP and one male receiving 300 ppm for 13
      weeks. There were no other histopathological findings. All effects noted during
      the treatment period, including the duodenal hyperplasia, were reversible during
      the 6-week recovery period. Females dosed with 300-3000 ppm HP during the
      treatment period showed increased water consumption during the recovery period.
      The no-observed-effect level (NOEL), based on duodenal mucosal hyperplasia, is
      100 ppm in drinking water or 26 and 37 mg/kg/day HP, respectively, for males and
      females.

PMID- 10942323
TI  - Subchronic toxicity of chlorpropham (CIPC) in ICR mice.
AB  - Male and female ICR mice were given 0, 1875, 7500 or 30,000 ppm of chlorpropham
      (CIPC) in the diet for 13 weeks. Methemoglobin levels of male and female mice in
      the 7500 and 30,000 ppm groups were significantly elevated. Hemoglobin
      concentration, packed cell volume, mean corpuscular volume, mean corpuscular
      hemoglobin, mean corpuscular hemoglobin concentration and white blood cell count
      of male and female mice in the 30,000 ppm group were significantly increased.
      Dose-dependent splenomegaly was observed in male and female mice in the 7500 and
      30,000 ppm group. Congestion, increased hemosiderin deposition and increased
      extramedullary hematopoiesis in the spleen, hematopoietic cell hyperplasia and
      hemosiderin deposition in bone marrow was observed dose dependently in male and
      female mice in the 7500 or 30,000 ppm group. Eosinophilic granular cytoplasm of
      hepatocytes, sinusoidal dilatation, hemosiderin deposition, extramedullary
      hematopoiesis and necrosis of hepatocytes were observed in the liver of male and
      female mice in the 30,000 ppm group. Hemosiderin deposition was increased in the
      kidney of male and female mice in the 30,000 ppm group. Administration of CIPC in
      diet for 13 weeks caused methemoglobinemia and splenomegaly in ICR mice.

PMID- 10942324
TI  - Direct and translactational effect of arecoline alkaloid on the clocimum oil
      modulated hepatic drug metabolizing enzymes in mice.
AB  - The present study assesses the potential of arecoline alkaloid, by direct
      exposure in lactating dams and translactational exposure in neonates, to modulate
      the efficacy of clocimum oil as a blocking agent in chemopreventive pathway.
      Clocimum oil (25 or 50 microl/dam/day) induced a significant increase in the
      hepatic levels of phase II glutathione S-transferase (GST) and acid-soluble
      sulfhydryl in lactating dams and suckling neonates while the elevated levels of
      hepatic phase I cytochrome b5 (Cyt. b5) and cytochrome P-450 (P450) were observed
      only in the dams. Arecoline (0.6 mg/dam/day) alone did not modulate the hepatic
      GST and sulfhydryl levels in either dams or pups, although significant induction
      was observed in the hepatic levels of Cyt. b5, P450 and malondialdehyde (MDA) in
      lactating dams and suckling neonates. Clocimum oil-modulated hepatic levels of
      phase II components were depressed whereas phase I enzymes and lipid peroxides
      levels were further elevated by clocimum oil-plus-arecoline treatment. The direct
      or translactationally augmented levels of bioactivated species of the
      administered compounds, via enhanced phase I oxidative catalysis and less
      efficient GST/GSH conjugational detoxication, may suggest the antagonistic
      influence of arecoline on chemopreventive efficacy of clocimum oil.

PMID- 10942326
TI  - Tumour growth while waiting: does it really matter?

PMID- 10942325
TI  - The relative toxicity of compounds in mainstream cigarette smoke condensate.
AB  - Many different in vivo and in vitro tests are currently used to assess the
      toxicity of chemicals and complex mixtures such as cigarette smoke condensate. In
      vivo tests include assays in rodents to determine carcinogenicity, tumorigenicity
      and reproductive effects In vitro tests of mutagenicity are conducted with both
      bacterial and mammalian cell systems. A first step towards lowering the toxicity
      of cigarette smoke condensate is the identification of the relevant compound
      However, changing the concentration of a given smoke component may not linearly
      alter the biological activity of the complex mixture due to interactive effects.
      The "effective toxicity" of a chemical constituent is a function of the
      concentration, the metabolic fate, the potency in in vivo and in vitro assays,
      and the ability to reach the target tissues. The logarithm of the octanol-water
      partition coefficient (log P) is an important parameter since it affects
      metabolism, biological transport properties and intrinsic toxicity. Using
      concentration data from the International Agency for Cancer Research (IARC),
      biological activity data from the Registry of Toxic Effects of Chemical
      Substances (RTECS) database and measured and calculated log P values, we have
      rank ordered some of the important compounds in cigarette smoke condensate by
      their measured or potential toxicity. Condensates from different cigarette
      brands, tar categories and styles vary in their concentrations of these
      compounds. Chemicals of greater commercial or scientific interest may be toxicity
      tested more extensively, thereby increasing the probability of positive test
      results and highlighting the need for consideration of structure-activity
      relationships.

PMID- 10942327
TI  - Waiting times for cancer treatment.

PMID- 10942328
TI  - Lung cancer treatment waiting times and tumour growth.
AB  - We report a single-centre prospective audit of 29 lung cancer patients who were
      awaiting radical (potentially curative) radiotherapy. This was the total number
      assessed as suitable for radical treatment by one consultant during 1999. At the
      time of assessment they had been newly diagnosed and staged with a computed
      tomographic (CT) scan of chest. They had a subsequent CT scan prior to starting
      treatment for the purpose of planning the radiation fields. We have now measured
      tumour size on the diagnostic scans and compared this with the size on the
      planning scans. We have documented the delay between diagnostic and planning CT
      scanning and the total time between first hospital visit and starting treatment.
      Two patients had progression of symptoms while on the waiting list, making them
      unfit for radical treatment, and another four had tumour progression on planning
      CT such that the tumour volume was too large for radical treatment. Therefore,
      21% of potentially curable patients became incurable on the waiting list. The
      delay between diagnostic and planning CT scans ranged from 18 to 131 days (median
      54), with increases in the cross-sectional tumour size over that period ranging
      zero to 373%. The delay between the first hospital visit and starting treatment
      was 35-187 days (median 94); between the date of the radiotherapy request and the
      starting date for treatment it was 23-61 days (median 44). Limited access to
      specialists is the reason most often advanced for the poor performance of the UK
      in treating lung cancer. This study demonstrates that, even for the select
      minority of patients who have specialist referral and are deemed suitable for
      potentially curative treatment, the outcome is prejudiced by waiting times that
      allow tumour progression.

PMID- 10942329
TI  - Anthracyclines and cardiotoxicity.

PMID- 10942330
TI  - Anthracyclines and cardiotoxicity.

PMID- 10942331
TI  - A doxorubicin-based regimen used in the treatment of elderly patients with high
      grade non-Hodgkin's lymphoma.
AB  - A retrospective analysis was performed on 66 patients, aged 70 years or older,
      who received treatment with a weekly doxorubicin-containing regimen (VAPEC-B) for
      high grade non-Hodgkin's lymphoma (NHL). Two dosing schedules were employed. The
      choice of regimen was at the discretion of the treating clinician and reflected
      the performance status of the patient and the predicted tolerance to
      chemotherapy. Forty-nine patients received a half-dose schedule and 17 the full
      dose schedule. Those receiving the half-dose regimen had a lower median
      performance status and received a lower dose intensity of chemotherapy (45%
      versus 83%). However, the outcomes of the two groups were similar: complete
      remission rate 41% versus 47%, and 5-year overall survival 36% versus 23%, for
      the half- and full-dose groups, respectively. A similar proportion of patients
      (51% versus 59%) completed each regimen, although there were more delays in
      treatment delivery experienced in those receiving the full dose. Half-dose VAPEC
      B is an effective treatment option for elderly patients with high-grade NHL and
      has comparable efficacy with other published regimens. The use of such low-dose
      doxorubicin-containing regimens in elderly patients with high-grade NHL requires
      further investigation.

PMID- 10942332
TI  - The role of radiotherapy in patients undergoing mastectomy for carcinoma of the
      breast.
AB  - Several factors, including T stage, nodal involvement, grade, the presence of
      lymphovascular invasion, and possibly involved or close surgical margins, have
      been found to affect local recurrence after mastectomy. The majority of
      recurrences will occur in the first 5 years and 50% of patients will have
      metastatic disease at the time of recurrence. Early studies on the use of
      adjuvant radiotherapy are difficult to interpret owing to poor radiotherapy
      techniques, inadequate dose or a variety of confounding variables within a
      particular trial. More recent reports have confirmed that adjuvant radiotherapy
      will reduce the risk of local recurrence and in tumours of <5 cm with involved
      nodes, produce a reduction in breast cancer deaths. Improvements in breast cancer
      mortality may however be counterbalanced by increases in cardiac events and
      deaths caused by second malignancies. This stresses the importance of using
      megavoltage irradiation and avoiding excess cardiac doses particularly when
      treating left-sided tumours. Adjuvant radiotherapy combined with tamoxifen has
      been shown to produce an improvement in both local control and survival in
      postmenopausal node-positive patients who have undergone mastectomy. Adjuvant
      radiation combined with systemic chemotherapy has a significant effect on local
      recurrence and probably on survival in node-positive patients after mastectomy.
      There is little controversy over its role in patients with tumours >5 cm, with
      more than four nodes involved or with one to three nodes with extracapsular
      extension, or in those in whom axillary surgery has been deemed inadequate (i.e.
      <10 nodes). Debate still exists concerning T1/T2, G1/G2 tumours with only one to
      three nodes involved when the axillary surgery has been satisfactory (>10 nodes).
      The ongoing Intergroup trial may answer this question but until then other
      factors such as tumour grade and the presence of lymphovascular invasion can be
      included in the equation to determine which of the patients in the latter group
      should receive postoperative radiotherapy. Controversy still exists about what
      fields should be irradiated and in particular whether the supraclavicular fossa
      and internal mammary node chain should be included in adjuvant therapy. The EORTC
      is presently conducting a randomized trial, which should give us the answer.
      Treatment at relapse on the chest wall may require a combination of surgery,
      radiotherapy and chemotherapy, depending on previous therapy. If radiotherapy has
      not previously been used, then wide-field irradiation should be administered,
      including both chest wall and supraclavicular fossa with or without the axilla,
      depending on the extent of previous axillary surgery and the risk of lymphoedema.
      Re-irradiation after radical adjuvant radiotherapy can be considered only for
      selected patients when an adequate discussion with them has taken place with
      regard to the relative benefits versus toxicity.

PMID- 10942333
TI  - Fine-needle aspiration cytology in tumour diagnosis: uses and limitations.

PMID- 10942334
TI  - An audit of indications and techniques for supraclavicular fossa irradiation in
      early breast cancer in the United Kingdom.
AB  - This article describes an audit of the indications and techniques used by
      clinical oncologists in the United Kingdom (UK) in the delivery of adjuvant
      radiotherapy to the supraclavicular fossa (SCF) in patients with early breast
      cancer. A postal questionnaire was sent to one consultant clinical oncologist in
      each UK radiotherapy centre in November 1999. These were the same individuals
      listed in the Maher Committee Report as providing breast cancer services. Forty
      one out of 51 completed forms were returned. The results show significant
      variation in the indications for SCF irradiation and for the definition of the
      radiotherapy target volume. We discuss the possible basis for the variations
      found in the audit. There was broad agreement on technique, in particular on the
      need for matching the tangential and SCF fields and maintaining patient position
      between fields, factors that are likely to minimize serious morbidity, including
      brachial plexus injury.

PMID- 10942335
TI  - Palliative care activity in a medical oncology unit: the implications for
      oncology training.
AB  - There has been a nationwide reorganization of cancer services since publication
      of the Calman-Hine report, which encourages the integration of high-quality
      palliative care into all areas of cancer provision. Details of the daily clinical
      care activity for medical oncology inpatients are not collected routinely. A
      prospective survey of activity was carried out in a large teaching hospital, in
      order to ascertain the extent to which palliative care is exercised in a medical
      oncology unit, alongside other aspects of care provision. Almost a quarter (23%)
      of the admissions were for palliative care, either alone or in combination with
      another aspect of care. Palliative care activity accounted for 34% (169 bed-days)
      of daily activity, compared with 32% (163 bed-days) for the administration of
      chemotherapy. A high proportion of patients receive palliative care on medical
      oncology wards, consideration therefore needs to be given to the place of formal
      training in palliative medicine for oncology trainees.

PMID- 10942336
TI  - Preoperative ECF chemotherapy in gastro-oesophageal adenocarcinoma.
AB  - Epirubicin, cisplatin and continuous 5-fluorouracil (5-FU) infusion (ECF) has
      been reported to result in high clinical response rates in advanced gastro
      oesophageal adenocarcinoma and is currently the 'gold standard' chemotherapy
      regimen for this tumour site. Despite this, its role as preoperative
      (neoadjuvant) treatment is unproven and therefore remains under investigation. We
      report our experience using ECF (intravenous epirubicin 50 mg/m2 and cisplatin 60
      mg/m2 every 3 weeks, with continuous infusion of 5-FU 200 mg/m2 per day) as
      preoperative treatment in locally advanced adenocarcinoma of the lower
      oesophagus, gastro-oesophageal junction and stomach. Of the 23 patients treated
      (median age 54 years), 19 had potentially resectable disease, four were
      unresectable and seven had radiological evidence of lymph node involvement. A
      median of four cycles of ECF was delivered (range 1-6). Ten of 12 patients (83%)
      with dysphagia reported improvement of symptoms. Clinical disease progression
      occurred in six patients (26%) during chemotherapy. WHO grade 3 or 4 toxicity
      occurred in six patients (26%): four haematological, one mucositis, one vomiting.
      Seventeen patients (74%) proceeded to surgery; 14 (61%) were resected and three
      were unresectable. There were two (12%) postoperative deaths from respiratory
      failure. Major pathological response was seen in three patients (13%): one
      pathological complete response, two microscopic residual disease. Two patients
      had Stage II (T2N(0-1)) disease and nine were Stage III (T(3-4)N(0-1)). None of
      the patients with initially unresectable disease was rendered resectable. After a
      median follow-up interval of 33 months (range 26-53), the overall median survival
      was 12 months and 2-year survival was 30%. All patients who were initially
      unresectable or had radiological evidence of lymph node involvement have died.
      Therefore, despite good symptomatic response rates, ECF chemotherapy given in the
      preoperative setting did not appear to improve the outcome of patients with
      unresectable or radiologically lymph node-positive gastro-oesophageal
      adenocarcinoma. The role of ECF chemotherapy in resectable tumours is unclear and
      is currently under investigation in the randomized MRC Adjuvant Gastric
      Infusional Chemotherapy (MAGIC) study.

PMID- 10942337
TI  - Restoration of vision by radiotherapy for severe, acute, steroid-refractory,
      congestive thyroid orbitopathy.
AB  - We report the case history of a patient treated with radiotherapy for severe
      acute thyroid orbitopathy that failed to respond to high-dose corticosteroid
      therapy. The clinical response to irradiation was rapid, dramatic and sustained
      after extended follow-up. Although radiotherapy has been used in dysthyroid eye
      disease, there remains debate over the precise indications for and the timing of
      its utilization. A review of the literature on the use of radiotherapy for acute
      thyroid orbitopathy has been undertaken, emphasizing its steroid-sparing
      potential and its role in avoiding the necessity for surgical orbital
      decompression.

PMID- 10942338
TI  - Psoriasis and radiotherapy: exacerbation of psoriasis following radiotherapy for
      carcinoma of the breast (the Koebner phenomenon).
AB  - We report the case history of a patient with a known history of psoriasis, who
      developed an exacerbation of the treated skin area after radiotherapy for
      carcinoma of the breast. This illustrates the Koebner phenomenon, with the
      replication of a dermatosis at the site of skin trauma.

PMID- 10942339
TI  - Absence of immunohistochemical evidence for human herpesvirus 8 (HHV8) in oral
      cavity plasmablastic lymphoma in an HIV-positive man.

PMID- 10942341
TI  - Should we discuss smoking histories with our cancer patients?

PMID- 10942340
TI  - Chylothorax due to carcinoid tumour.

PMID- 10942343
TI  - Age, sex and anthropometric status of children in an African pastoral community.
AB  - The study objective was to explore sex differences in anthropometric status of
      children from a semi-nomadic population of Datoga pastoralists living in northern
      Tanzania and test the hypothesis that any differences would be related to age-
      and gender-specific work activities. Anthropometric measurements made on 438
      individual children (0-18 years) were used to assess the association of various
      anthropometric measures of achieved growth status with age, sex and season of
      measurement. There was a high overall prevalence of indicators of undernutrition
      but the risk of undernutrition was not uniformly distributed within the child
      population. Comparison of cross-sectional mean anthropometric scores suggested
      that children over 5 years, girls 5-8 years, boys 9-12 years and teenagers were
      found to be at highest risk of undernutrition as assessed by various indicators.
      Although the prevalence of all indicators of undernutrition showed a significant
      increase with age, the prevalence of indicators of undernutrition did not show a
      statistically significant sex difference within any age group. There was little
      evidence of sex-preferential treatment of children or strongly biased sex ratios
      or mortality rates. Taken together, these results indicate that the
      anthropometric status of children may be associated with the age- and gender
      specific pattern of work activities typical of this population. Possible
      mechanisms through which anthropometric status may be influenced by work
      activities are hypothesized.

PMID- 10942342
TI  - Bone mineral density in older non-Hispanic Caucasian and Mexican-American women:
      relationship to lean and fat mass.
AB  - PRIMARY OBJECTIVE: The prevalence of osteoporotic fracture is higher in non
      Hispanic Caucasian (NHC) than Mexican-American (MA) women in the USA. The present
      study examined bone mineral density (BMD) in these two ethnic groups and the
      association between BMD and body composition. RESEARCH DESIGN: Cross-sectional.
      SUBJECTS: Sixty-two NHC and 54 MA women, aged 60-86 years, with a body mass index
      (kgm(-2)) of <30. METHODS: BMD (gcm(-2)) of the spine (L2-4), hip (femoral neck,
      trochanter, Ward's triangle) and whole body was determined by dual-energy X-ray
      absorptiometry (DXA). Bone mineral-free lean mass (LM) and fat mass (FM) and
      several ratios of body fat distribution were also assessed by DXA. RESULTS: There
      was no difference in age (NHC, 69.5+/-0.7; MA 69.5+/-0.9 years; mean +/- SEM) or
      body mass, but MA women were shorter with a higher truncal adiposity (p < 0.001).
      There was no significant difference in BMD between groups, however, adjusting for
      height resulted in higher hip and whole body BMD in MA women (p < 0.01). When
      volumetric bone density was calculated (bone mineral apparent density; BMAD, gcm(
      3)), a trend for higher values in MA women was observed at the femoral neck (p =
      0.018). LM contributed independently to BMD at the spine and hip in NHC women,
      with FM also contributing at the femoral neck. In MA women, LM was an independent
      contributor to lumbar spine and trochanter BMD, and both LM and FM contributed to
      whole body BMD. However, the effects of LM and FM were removed in both groups
      when BMD was adjusted for body or bone size, the only exception being at the
      trochanter in NHC women. CONCLUSIONS: These results indicate that MA women have
      higher bone density at the proximal femur than NHC women, which may partially
      account for their lower rate of hip fracture. Further, differences in bone
      density between the two ethnic groups do not appear to be dependent on soft
      tissue composition.

PMID- 10942345
TI  - A continuous decline in menarcheal age in Denmark.
AB  - We report a renewed decline in mean menarcheal age in a large Danish sample after
      a period with a halt in the trend towards earlier age at menarche in many North
      European countries. In our study based on retrospective data from six different
      samples constituting 42784 women, we find a continuously declining mean
      menarcheal age in Denmark among women born in the years 1964-1973. In a sample of
      textile workers born in the years 1939-1968 (n = 12605) we find a 1 year higher
      mean menarcheal age. This indicates that menarcheal age is still delayed in
      certain groups in Denmark. This leaves the possibility that the menarcheal age
      could fall even further in the future.

PMID- 10942344
TI  - Cord blood apolipoprotein-E genotype distribution and plasma lipid indices in
      newborns of different ethnicity.
AB  - We hypothesized that apolipoprotein-E (apo-E) genotypes would be associated with
      plasma lipid indices in newborns of South Asian (SA) ancestry but not in newborns
      of African (Afr) ancestry. Cord blood was obtained by consecutive sampling at
      maternity hospitals in the Caribbean Islands of Trinidad and Curacao.
      Apolipoprotein-E genotypes, cholesterol, triglycerides, apo-A, apo-B and
      Lipoprotein (a) (Lp(a)) were measured in 294 newborns in Trinidad and 234 in
      Curacao. The apo-B/apo-AI ratio and an adapted lipid tetrad index (i.e.
      cholesterol x triglycerides x Lp(a)/apo-AI) were calculated. In Trinidad, apo-E
      allele frequencies and genotype distributions of Afr and SA were significantly (p
      < 0.001) different (Afr: n = 71: apo-e2 : e3 : e4 = 10.4 : 66.4 : 23.2%; SA: n =
      98; e2 : e3 : e4 = 3.5 : 83.1: 13.4%). The Mixed group (SA + Afr) had apo-E
      allele frequencies in between those of SA and Afr groups (n = 115; e2 : e3 : e4 =
      7 : 76 : 17%). Lipid indices of appropriate for gestational age and term newborns
      were comparable, except for lower Lp(a) (SA = 29+/-4; Afr = 46+/-5; Mixed = 41+/
      5 mg L(-1)) and lower adapted lipid tetrad index (29.4+/-4.8; 41.9+/-5.4; 41.4+/
      7.0) in SA. Apo-E allele frequencies of Curacao newborns were: apo-e2 : e3 : e4 =
      10.5 : 72.6 : 16.9%. Their Lp(a) levels were significantly higher (68+/-3 mg L(
      1)) than that of the Trinidadian sample (38+/-3; p < 0.0001). Apolipoprotein-E4
      had an apo-B-increasing effect and apo-E2 an apo-B-decreasing effect in Afr (r =
      0.192, p = 0.003). Among Africans from Trinidad and Curacao variations in apo-E4
      and apo-E2 are associated with an apo-B-increasing effect and an apo-B-decreasing
      effect, respectively. There was no relationship between apo-E polymorphism and
      lipids among South Asians.

PMID- 10942346
TI  - Morphology and performance of world championship triathletes.
AB  - Performance is related to body morphology in many sports. With triathlon making
      its debut into the Olympic programme in 2000, it was deemed important to
      determine which physical characteristics of elite-level triathletes were
      significantly related to performance. Seventy-one elite and junior elite
      triathletes, from 11 nations, competing at the 1997 World Triathlon Championships
      were measured on a battery of 28 anthropometric dimensions. A factor analysis was
      conducted, which reduced the number of variables to four and these were used in a
      stepwise linear regression to determine which morphological factors were
      important to performance. Elite triathletes were significantly (p < 0.05) faster
      than their junior counterparts (males 1:52:26 vs. 2:03:23 and females 2:07:01 vs.
      2:14:05) and showed less variation in performance times. Run time variation was
      the largest of the component disciplines and tended to show the importance of
      this discipline to the final outcome. Following a factor analysis the four
      distinguishable morphological factors that emerged were: robustness, adiposity,
      segmental lengths and skeletal mass. Relating these factors to the total time
      obtained by the triathletes in this study yielded a regression equation that
      correlated significantly with all triathletes, accounting for 47% of the variance
      in total triathlon duration. The regression equations illustrated the importance
      of low levels of adiposity for elite triathletes for total time and most of the
      subdisciplines. The other factor that showed importance was that proportionally
      longer segmental lengths contributed to successful swimming outcome.

PMID- 10942347
TI  - Galton's midparent height revisited.
AB  - Galton (Journal of the Anthropological Institute of Great Britain and Ireland,
      15, 246-263, 1886) defined midparent height as the average of the two parental
      heights. An alternative is to average the parental heights after converting them
      to standard deviation scores (SDSs). The aim of the paper is to compare the two
      midparent height calculations, and to see if they explain the imputation
      procedure used by Galton to adjust for the difference in adult height between
      daughters and sons. He multiplied daughters' heights by 1.08 before averaging
      them with sons' heights. Using data from 17 national height references it is
      shown that this procedure is equivalent to averaging the height SDSs of the sons
      and daughters. It demonstrates that midparent height SDS obtained by averaging
      the height SDSs of the two parents is a valid alternative to conventional
      midparent height.

PMID- 10942348
TI  - Persistent variations in average height between countries and between socio
      economic groups: an overview of 10 European countries.
AB  - PRIMARY OBJECTIVES: This paper aims to provide an overview of variations in
      average height between 10 European countries, and between socio-economic groups
      within these countries. DATA AND METHODS: Data on self-reported height of men and
      women aged 20-74 years were obtained from national health, level of living or
      multipurpose surveys for 1987-1994. Regression analyses were used to estimate
      height differences between educational groups and to evaluate whether the
      differences in average height between countries and between educational groups
      were smaller among younger than among older birth cohorts. RESULTS: Men and women
      were on average tallest in Norway, Sweden, Denmark and the Netherlands and
      shortest in France, Italy and Spain (range for men: 170-179 cm; range for women:
      160-167 cm). The differences in average height between northern and southern
      European countries were not smaller among younger than among older birth cohorts.
      In most countries average height increased linearly with increasing birth-year
      (approximately 0.7-0.8 cm/5 years for men and approximately 0.4 cm/5 years for
      women). In all countries, lower educated men and women on average were shorter
      than higher educated men (range of differences: 1.6-3.0 cm) and women (range of
      differences: 1.2-2.2 cm). In most countries, education-related height differences
      were not smaller among younger than among older birth cohorts. CONCLUSIONS: The
      persistence of international differences in average height into the youngest
      birth cohorts indicates a high degree of continuity of differences between
      countries in childhood living conditions. Similarly, the persistence of education
      related height differences indicates continuity of socio-economic differences in
      childhood living conditions, and also suggests that socio-economic differences in
      childhood living conditions will continue to contribute to socio-economic
      differences in health at adult ages.

PMID- 10942349
TI  - Secular trend in age at menarche for women born between 1920 and 1979 in Rio de
      Janeiro, Brazil.
AB  - PRIMARY OBJECTIVE: This article presents data on the secular trend in age at
      menarche for 1955 women from 16 to 76 years of age born between 1920 and 1979 and
      studied under the Nutrition and Health Survey conducted in the municipality of
      Rio de Janeiro, Brazil, in 1996. METHODS AND PROCEDURES: Age at menarche was
      defined by the retrospective method. Women were grouped according to decade of
      birth, and the trend was estimated using simple linear regression between age at
      menarche and year of birth for the following specific periods: 1920-1940, 1920
      1960, 1960-1979 and 1920-1979. MAIN OUTCOMES AND RESULTS: Mean age at menarche
      decreased from 13.07 to 12.40 years when comparing the group of women born in the
      1920s with the 1970s birth cohort, corresponding to a mean rate of -0.0123 years
      per year (p < 0.001). The downward trend was -0.0120 years per year (p > 0.05)
      for the 1920s, 30s and 40s, -0.0093 years per year (p < 0.05) for the period from
      1920 to 1960, and -0.0224 years per year (p < 0.01) for the 1960s/70s.
      CONCLUSIONS: The results suggest a secular trend in age at menarche. The
      literature points to such environmental variables as improved living conditions
      and expanded access to health services. Within this context, age at menarche
      could be used as a marker for social development.

PMID- 10942350
TI  - Re: Identifying population differences in lung function: results from the Allied
      Dunbar national fitness survey.

PMID- 10942351
TI  - Adolescent sexual behavior: estimates and trends from four nationally
      representative surveys.
AB  - CONTEXT: Accurate information about trends over time in adolescent sexual
      behavior is essential to understand changes in adolescent pregnancy and sexually
      transmitted diseases and to monitor the progress of health promotion activities
      in the United States METHODS: Estimates from the National Survey of Family Growth
      (NSFG), the National Survey of Adolescent Males (NSAM), the Youth Risk Behavior
      Survey (YRBS) and the National Longitudinal Study of Adolescent Health (Add
      Health) were compared. While methodologies and populations varied by survey,
      adolescents aged 15-17 who attend high school were a common subpopulation among
      all four. For each survey, the prevalence of sexual intercourse, contraceptive
      use and multiple sexual partners was measured in this population. RESULTS: Trend
      comparisons fell into four categories. First, some similar significant trends
      were found across surveys. The proportion of all males and of white males who
      reported ever having had sexual intercourse decreased significantly, while condom
      use rose significantly among males in both the NSAM and the YRBS. For such
      behaviors as ever having had sexual intercourse (among Hispanic males and black
      females), using the pill and using the condom (among all females) and having four
      or more lifetime sexual partners (among white males), a significant trend was
      found in one survey while a similar but nonsignificant trend was found in
      another. Several trend comparisons were not significant in any survey. Finally,
      having had intercourse in the past three months (among all males and all
      females), having had two or more partners in the past three months (for males)
      and having had four or more lifetime sexual partners (among white females and all
      males) showed a significant trend in one survey but lacked a parallel
      nonsignificant trend in another. Prevalence estimates in 1995 differed
      significantly in at least one comparison of surveys for all behaviors except
      having four or more lifetime sexual partners (both genders) and having two or
      more recent sexual partners (females). Gender differences within the YRBS and
      between the NSFG and the NSAM generally were consistent. CONCLUSIONS: Trends over
      time and gender differences were similar across surveys, underscoring their value
      for tracking adolescent sexual behaviors. Differences in prevalence estimates
      across surveys probably result from differences in question wording, diverse
      interview settings and modes of data collection, and varying statistical power.
      These findings suggest a need to increase our understanding of how methodologies
      influence survey response in research on adolescents.

PMID- 10942352
TI  - Explaining demographic trends in teenage fertility, 1980-1995.
AB  - CONTEXT: The teenage birthrate rose sharply in the late 1980s and early 1990s,
      and then declined in the 1990s. Attempts to explain these changes have failed to
      account for the changing environment in which adolescents live. METHODS: Data
      from the 1995 cycle of the National Survey of Family Growth are used to compare
      the experiences of three cohorts of teenage females in the 1980s and 1990s. A
      life-course framework is used to examine trends in characteristics of adolescents
      and adolescent mothers over time, and event-history analyses are conducted to
      determine which characteristics are associated with the risk of a teenage birth
      in each cohort. A comparison of the predicted probabilities from hazard analyses
      shows how changes in the context of adolescence across the cohorts help explain
      changes in the probability of a teenage birth over time. RESULTS: Factors
      associated with the increase in the teenage birthrate in the 1980s include
      negative changes in family environments (such as increases in family disruption)
      and an increase in the proportion of teenagers having sex at an early age.
      Factors associated with the recent decline in the teenage birthrate include
      positive changes in family environments (such as improvements in maternal
      education), formal sex education programs and discussions with parents about sex,
      stabilization in the proportion of teenagers having sex at an early age and
      improved contraceptive use at first sex. Sexually experienced teenagers in the
      mid- 1990s were younger, on average, at first sex than were their counterparts in
      the 1980s, and thus are at an increased risk of a teenage birth. Partner factors,
      including nonvoluntary first sexual experiences, were not associated with the
      risk of a adolescent birth in any cohort. CONCLUSIONS: Programs to further reduce
      the teenage birthrate should take into account the role of family stability,
      parent-child communication, sex education programs and engagement in school, as
      well as attempt to reduce the proportion of adolescents having sex at an early
      age and to improve contraceptive use. The increasing risk levels among sexually
      experienced teenagers suggest that current programs may be reducing sexual
      activity among adolescents already at a low risk of a teenage birth, without
      addressing the needs of those at highest risk.

PMID- 10942353
TI  - Why are US women not using long-acting contraceptives?
AB  - CONTEXT: Given the level of unintended pregnancy in the United States, it is
      somewhat surprising that hormonal implants and injectables-methods that are long
      acting, reversible, highly effective and convenient--have not attained the
      popularity enjoyed by other medical methods. Knowing the reasons why women have
      so far spurned these methods might lead to the design and implementation of
      interventions and targeted social marketing to promote their use. METHODS: Data
      from the 1993 and 1995 rounds of the National Survey of Women are used to examine
      the reasons women gave for not having used the implant or injectables, whether
      they intended to use these methods and how their attitudes toward them may
      influence their decision to use such methods in the future. Logistic regression
      models were used to identify the social and demographic characteristics that
      influence women's decisions not to use these methods. RESULTS: Fewer than 2% of
      women who were at risk of an unintended pregnancy in 1995 were using the implant,
      and under 3% were using the injectable. Women gave three major reasons for not
      using either of these methods: lack of knowledge; fear of side effects or health
      hazards; and satisfaction with the method they were currently using. Age,
      education, marital status, parity and current contraceptive method strongly
      predicted fear of side effects, lack of knowledge and satisfaction with the
      current method as reasons for not using the implant or the injectable. For
      example, women aged 30 or older and those with a college education were half as
      likely as younger women and those with no college education to mention fear of
      side effects as their main reason for not using the implant. Likewise, single
      women, women with one or more children and those using a barrier method were 2-3
      times as likely as married women, childless women and those using a medical
      method to attribute nonuse to the implant's side effects. Few women said they
      intended to use these methods in the next 12 months: 5% for the implant and 10%
      for the injectable. Single women, women with no college education, women with
      children, women wanting to have a child (or another child) and women with
      positive attitudes toward the effect of using an injectable were significantly
      more likely to say they intended to use the injectable. Nevertheless, substantial
      proportions of women reported quite negative attitudes about these methods.
      CONCLUSIONS: The low prevalence of use and the low level of use intention for the
      implant and for injectables raise questions about the promise for the future of
      these methods. Each method seems to appeal to certain subgroups of women,
      however. Thus, if proper interventions and social marketing are targeted to such
      groups, they may be disabused of misperceptions regarding these methods and
      possibly become more willing to try them.

PMID- 10942354
TI  - Acceptability of a novel vaginal microbicide during a safety trial among low-risk
      women.
AB  - CONTEXT: The increasing recognition that women who are unable or unwilling to
      discuss or use condoms with their sexual partners need female-controlled methods
      for preventing sexually transmitted diseases (STDs), including HIV, has led to
      considerable focus on the development of vaginal microbicides. While many such
      products are being tested for safety and effectiveness, clinical trials generally
      overlook another key factor in a product's impact on infection rates-its
      acceptability to users. METHODS: A Phase I clinical trial of a microbicidal gel
      included an assessment of the product's acceptability among 27 low-risk
      participants. Information on acceptability was gathered from structured
      interviews, participants' daily diaries and unstructured exit interviews.
      RESULTS: Participants reported only minor side effects of product use, such as
      itching, burning and difficulty urinating; two women developed candida infections
      while participating in the study. None of the side effects could be conclusively
      linked to use of the gel. Some women noted product discharge and messiness as
      drawbacks of the method, but this experience varied according to how often the
      women applied the gel. For example, one-third of those who used it once daily
      said that at least some of the time, it was too "wet or drippy," compared with
      two-thirds of women who inserted the gel twice a day. However, participants
      considered these "nuisance factors" that could be outweighed by the potential
      protective characteristics of the product. The majority reported that they would
      use the product if it were available and proven efficacious, and if they
      perceived that they were at risk of STD infection. CONCLUSIONS: Additional
      testing of this product is urgently needed. Furthermore, as other products
      approach Phase I testing, acceptability assessments should be a key component of
      clinical trials.

PMID- 10942355
TI  - British general practitioners' attitudes toward abortion.
AB  - CONTEXT: Women in Great Britain may obtain abortions only if they meet certain
      criteria and the procedure is approved by two physicians. Since seeing a general
      practitioner is typically a woman's first step toward obtaining an abortion,
      these doctors' attitudes about the procedure are very important. METHODS: In
      1999, a random sample of 702 general practitioners participated in a mailed
      survey regarding their attitudes toward abortion and the British Abortion Act.
      RESULTS: Four in five respondents considered themselves broadly prochoice, and
      three in five believed that the current law should be liberalized to give women
      the right to obtain an abortion without regard as to reason. Three-quarters of
      doctors favored government provision of free abortions, and one-quarter thought
      that the current law places an unreasonable burden on general practitioners.
      However, physicians' opinions about whether the abortion decision should be the
      woman's alone depended on the pregnancy's gestation, and three-fifths of
      respondents said that the law was appropriate. Among doctors who were broadly
      antiabortion, one-fifth favored women's right to choose, and two-thirds supported
      the current law; however, nearly half opposed government funding of abortion
      services, and one-quarter did not feel that physicians need to reveal their
      antiabortion stance to patients. CONCLUSIONS: Although Great Britain's abortion
      law is more restrictive than those in many other developed countries, general
      practitioners have largely positive attitudes toward women's access to abortion
      and toward the existing law. Their occasionally contradictory views, however,
      suggest that some areas are potentially problematic.

PMID- 10942356
TI  - Has Canadian contraceptive use really declined?

PMID- 10942358
TI  - "How I treat": a new style of clinical review article

PMID- 10942357
TI  - Understanding pregnancy intentions: a problem in evidence everywhere.

PMID- 10942359
TI  - Highly efficient gene transfer into cord blood nonobese diabetic/severe combined
      immunodeficiency repopulating cells by oncoretroviral vector particles
      pseudotyped with the feline endogenous retrovirus (RD114) envelope protein.
AB  - Limited expression of the amphotropic envelope receptor is a recognized barrier
      to efficient oncoretroviral vector-mediated gene transfer. Human hematopoietic
      cell lines and cord blood-derived CD34(+) and CD34(+), CD38(-) cell populations
      and the progenitors contained therein were transduced far more efficiently with
      oncoretroviral particles pseudotyped with the envelope protein of feline
      endogenous virus (RD114) than with conventional amphotropic vector particles.
      Similarly, human repopulating cells from umbilical cord blood capable of
      establishing hematopoiesis in immunodeficient mice were efficiently transduced
      with RD114-pseudotyped particles, whereas amphotropic particles were ineffective
      at introducing the proviral genome. After only a single exposure of CD34(+) cord
      blood cells to RD114-pseudotyped particles, all engrafted nonobese
      diabetic/severe combined immunodeficiency mice (15 of 15) contained genetically
      modified human bone marrow cells. Human cells that were positive for enhanced
      green fluorescent protein represented as much as 90% of the graft. The use of
      RD114-pseudotyped vectors may be advantageous for therapeutic gene transfer into
      hematopoietic stem cells. (Blood. 2000;96:1206-1214)

PMID- 10942361
TI  - How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic
      syndrome.
AB  - Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
      are, in adults, clinically and pathologically indistinguishable except for the
      severity of renal failure. They are best described as a single disorder, TTP-HUS,
      because the diagnostic evaluation and initial management are the same. Treatment
      with plasma exchange, available for more than 20 years, has dramatically altered
      the course of disease in adults with TTP-HUS. Plasma exchange has improved
      survival rates from 10% to between 75% and 92%, creating urgency for the
      initiation of treatment. This has resulted in decreased stringency of diagnostic
      criteria, which in turn has resulted in a broader spectrum of disorders for which
      the diagnosis of TTP-HUS is considered. Long-term follow-up has revealed
      increasing frequencies of relapse and of chronic renal failure. Although the
      increased survival rate is dramatic and recent advances in understanding the
      pathogenesis of these syndromes are remarkable, clinical decisions remain
      empirical. Therefore, the management decisions for patients with suspected TTP
      HUS rely on individual experience and opinion, resulting in many different
      practice patterns. Multipractice clinical trials are required to define optimal
      management. (Blood. 2000;96:1223-1229)

PMID- 10942360
TI  - A ligand-receptor signaling threshold model of stem cell differentiation control:
      a biologically conserved mechanism applicable to hematopoiesis.
AB  - A major limitation to the widespread use of hematopoietic stem cells (HSC) is the
      relatively crude level of our knowledge of how to maintain these cells in vitro
      without loss of the long-term multilineage growth and differentiation properties
      required for their clinical utility. An experimental and theoretical framework
      for predicting and controlling the outcome of HSC stimulation by exogenous
      cytokines would thus be useful. An emerging theme from recent HSC expansion
      studies is that a net gain in HSC numbers requires the maintenance of critical
      signaling ligand(s) above a threshold level. These ligand-receptor complex
      thresholds can be maintained, for example, by high concentrations of soluble
      cytokines or by extracellular matrix- or cell-bound cytokine presentation.
      According to such a model, when the relevant ligand-receptor interaction falls
      below a critical level, the probability of a differentiation response is
      increased; otherwise, self-renewal is favored. Thus, in addition to the identity
      of a particular receptor-ligand interaction being important to the regulation of
      stem cell responses, the quantitative nature of this interaction, as well as the
      dynamics of receptor expression, internalization, and signaling, may have a
      significant influence on stem cell fate decisions. This review uses examples from
      hematopoiesis and other tissue systems to examine existing evidence for a role of
      receptor activation thresholds in regulating hematopoietic stem cell self-renewal
      versus differentiation events. (Blood. 2000;96:1215-1222)

PMID- 10942362
TI  - CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from
      human cord blood induced by granulocyte-macrophage colony-stimulating factor:
      chemotaxis and adhesion induced by its ligands, interferon gamma-inducible
      protein 10 and monokine induced by interferon gamma.
AB  - CXC chemokine receptor 3 (CXCR3), which is known to be expressed predominately on
      memory and activated T lymphocytes, is a receptor for both interferon gamma (IFN
      gamma)-inducible protein 10 (gamma IP-10) and monokine induced by IFN-gamma
      (Mig). We report the novel finding that CXCR3 is also expressed on CD34(+)
      hematopoietic progenitors from human cord blood stimulated with granulocyte
      macrophage colony-stimulating factor (GM-CSF) but not on freshly isolated CD34(+)
      progenitors. Freshly isolated CD34(+) progenitors expressed low levels of CXCR3
      messenger RNA, but this expression was highly up-regulated by GM-CSF, as
      indicated by a real-time quantitative reverse transcriptase-polymerase chain
      reaction technique. gamma IP-10 and Mig induced chemotaxis of GM-CSF-stimulated
      CD34(+) progenitors by means of CXCR3, since an anti-CXCR3 monoclonal antibody
      (mAb) was found to block gamma IP-10-induced and Mig-induced CD34(+) progenitor
      chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming
      units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated
      CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding
      confirmed by the observation that anti-CXCR3 mAb blocked these functions of
      gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha.
      gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b)
      was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+)
      progenitors. Moreover, gamma IP-10 and Mig stimulated CXCR3 redistribution and
      cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results
      indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as
      the effects of GM-CSF on them, may be especially important in the
      cytokine/chemokine environment for the physiologic and pathophysiologic events of
      differentiation of CD34(+) hematopoietic progenitors into lymphoid and myeloid
      stem cells, subsequently immune and inflammatory cells. These processes include
      transmigration, relocation, differentiation, and maturation of CD34(+)
      hematopoietic progenitors. (Blood. 2000;96:1230-1238)

PMID- 10942363
TI  - Nonmyeloablative stem cell transplantation for congenital immunodeficiencies.
AB  - The optimal approach for stem cell transplantation in children with
      immunodeficiency has yet to be determined. Conditioning therapy is necessary for
      reliable engraftment and full immune reconstitution; however, the beneficial
      effect of cytoreductive conditioning is counterbalanced by increased short- and
      long-term treatment-related toxicity. Whether bone marrow transplantation with a
      nonmyeloablative preparative regimen was sufficient for the establishment of
      donor immune reconstitution, with the resultant correction of disease phenotype,
      was investigated. Eight patients with severe immunodeficiency states underwent T
      cell replete bone marrow transplantation from a human leukocyte antigen-matched
      unrelated (n = 6) or sibling (n = 2) donor with nonmyeloablative conditioning
      using a fludarabine-melphalan-anti-lymphocyte globulin-based regimen. All
      patients had severe organ dysfunction that precluded transplantation with
      conventional conditioning. All patients were engrafted with predominantly donor
      hematopoiesis, and the duration of neutropenia was brief. Significant acute graft
      versus-host disease (GVHD) did not develop, but one patient had limited chronic
      GVHD. One patient died of disease recurrence, and 3 have stable, mixed chimerism.
      At a median follow-up of 1 year, all patients have had good recovery of CD3(+) T
      cell numbers, and 6 of 7 evaluable patients have normal phytohemagglutinin
      stimulation indices. The rate of immune reconstitution is comparable with that of
      historical controls undergoing standard myeloablative protocols. Two patients
      with CD40 ligand deficiency now show significant expression, and a patient with
      adenosine deaminase deficiency has improved deoxy adenosine triphosphate
      metabolites. In summary, it has been demonstrated that nonmyeloablative stem cell
      transplantation permits rapid engraftment from both sibling and unrelated donors
      with minimal toxicity even in the presence of severe organ dysfunction. If long
      term immune reconstitution of patients treated with this protocol is
      demonstrated, it is believed this approach might offer significant advantages
      compared with standard protocols by combining adequate immune reconstitution with
      reduced short- and long-term toxicity. (Blood. 2000;96:1239-1246)

PMID- 10942364
TI  - Definition of relapse risk and role of nonanthracycline drugs for consolidation
      in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and
      GIMEMA cooperative groups.
AB  - Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA
      trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a
      similarly high antileukemic efficacy in terms of complete remission and disease
      free survival rates. To better investigate these studies and the prognostic
      factors influencing relapse risk, this study analyzed the updated results of 217
      patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA
      (n = 109). All patients received identical induction (AIDA schedule) and
      maintenance. For consolidation, GIMEMA patients received 3 courses including
      idarubicin/cytarabine, mitoxantrone/etoposide, and
      idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same
      drugs and dose schedule of idarubicin and mitoxantrone with the omission of
      nonintercalating agents. Depending on whether molecular relapses were classified
      as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse
      free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%,
      respectively. Minor differences observed between the 2 patient cohorts were
      negligible. Multivariate regression analysis of RFS showed that initial leukocyte
      (WBC) and platelet counts were the only variables with independent prognostic
      value. The resulting predictive model for RFS demonstrated its capability of
      segregating patients into low-risk (WBC count </= 10 x 10(9)/L, platelet count >
      40 x 10(9)/L), intermediate-risk (WBC count </= 10 x 10(9)/L, platelets </= 40 x
      10(9)/L), and high-risk (WBC count > 10 x 10(9)/L) groups, with distinctive RFS
      curves (P <.0001). The conclusions are that omission of nonanthracycline drugs
      from the AIDA regimen is not associated with reduced antileukemic efficacy and a
      simple predictive model may be used for risk-adapted therapy in this disease.
      (Blood. 2000;96:1247-1253)

PMID- 10942365
TI  - Effect of postremission chemotherapy before human leukocyte antigen-identical
      sibling transplantation for acute myelogenous leukemia in first complete
      remission.
AB  - Allogeneic bone marrow transplantation is an effective postremission strategy for
      patients with acute myelogenous leukemia (AML) in first complete remission (CR).
      The value of administering consolidation chemotherapy before human leukocyte
      antigen (HLA)-identical sibling transplantation is not established. Outcomes of
      patients with AML in first CR receiving no consolidation therapy, standard-dose
      cytarabine consolidation therapy, and high-dose cytarabine consolidation therapy
      before HLA-identical sibling transplantation were compared. Five-year treatment
      related mortality rates were 30% (95% confidence interval [CI], 18% to 42%) in
      patients receiving no consolidation chemotherapy, 22% (95% CI, 17% to 28%) in
      those receiving standard-dose cytarabine consolidation, and 24% (95% CI, 17% to
      31%) in those receiving high-dose cytarabine (P = NS). Five-year cumulative
      incidences of relapse were 19% (10% to 30%), 21% (16% to 27%), and 17% (11% to
      24%), respectively (P = NS). Five-year probabilities of leukemia-free survival
      were 50% (36% to 63%), 56% (49% to 63%), and 59% (50% to 66%), respectively (P =
      NS). Five-year probabilities of overall survival were 60% (46% to 71%), 56% (49%
      to 63%), and 60% (51% to 67%), respectively (P = NS). The data indicate that
      postremission consolidation with cytarabine before allogeneic transplantation for
      AML in first CR is not associated with improved outcome compared to proceeding
      directly to transplantation after successful induction. (Blood. 2000;96:1254
      1258)

PMID- 10942366
TI  - Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B
      cell non-Hodgkin lymphoma: updated results and long-term follow-up of the
      University of Michigan experience.
AB  - CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non
      Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59
      chemotherapy-relapsed/refractory patients treated with iodine (131)I tositumomab
      in a phase I/II single-center study. Fifty-three patients received individualized
      therapeutic doses, delivering a specified total-body radiation dose (TBD) based
      on the clearance rate of a preceding dosimetric dose. Six patients received
      dosimetric doses only. Dose-escalations of TBD were conducted separately in
      patients who had or had not undergone a prior autologous stem cell transplant
      (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT
      = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated
      with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and
      therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients
      responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low
      grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate
      grade NHL (P =.005). For all 42 responders, the median progression-free survival
      was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7
      years. Sixteen patients were re-treated after progression; 9 responded and 5 had
      a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%)
      had human anti-mouse antibodies detected. Long-term, 5 patients developed
      elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia
      and 3 with solid tumors. A single, well-tolerated treatment with iodine (131)I
      tositumomab can, therefore, produce frequent and durable responses in NHL,
      especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266)

PMID- 10942367
TI  - Soluble stem cell factor receptor (CD117) and IL-2 receptor alpha chain (CD25)
      levels in the plasma of patients with mastocytosis: relationships to disease
      severity and bone marrow pathology.
AB  - Systemic mastocytosis is a disease of mast cell proliferation that may be
      associated with hematologic disorders. There are no features on examination that
      allow the diagnosis of systemic disease, and mast cell-derived mediators, which
      may be elevated in urine or blood, may also be elevated in individuals with
      severe allergic disorders. Thus, the diagnosis usually depends on results of bone
      marrow biopsy. To facilitate evaluation, surrogate markers of the extent and
      severity of the disease are needed. Because of the association of mastocytosis
      with hematologic disease, plasma levels were measured for soluble KIT (sKIT) and
      soluble interleukin-2 receptor alpha chain (sCD25), which are known to be cleaved
      in part from the mast cell surface and are elevated in some hematologic
      malignancies. Results revealed that levels of both soluble receptors are
      increased in systemic mastocytosis. Median plasma sKIT concentrations as
      expressed by AU/mL (1 AU = 1.4 ng/mL) were as follows: controls, 176 (n = 60);
      urticaria pigmentosa without systemic involvement, 194 (n = 8); systemic indolent
      mastocytosis, 511 (n = 30); systemic mastocytosis with an associated hematologic
      disorder, 1320 (n = 7); aggressive mastocytosis, 3390 (n = 3). Plasma sCD25
      levels were elevated in systemic mastocytosis; the highest levels were associated
      with extensive bone marrow involvement. Levels of sKIT correlated with total
      tryptase levels, sCD25 levels, and bone marrow pathology. These results
      demonstrate that sKIT and sCD25 are useful surrogate markers of disease severity
      in patients with mastocytosis and should aid in diagnosis, in the selection of
      those needing a bone marrow biopsy, and in the documentation of disease
      progression. (Blood. 2000;96:1267-1273)

PMID- 10942368
TI  - B7-2-positive myeloma: incidence, clinical characteristics, prognostic
      significance, and implications for tumor immunotherapy.
AB  - Deficiencies in B7:CD28 costimulation are considered to be one of the major
      causes of the failure to generate a tumor-specific immune response. Up-regulating
      the expression of the B7 molecules on malignant B cells has been shown to
      stimulate cytotoxic T cells. Plasma cells from patients with myeloma express a
      tumor-specific idiotype but lack CD80 (B7-1) and have a variable expression of
      CD86 (B7-2). This study has identified the incidence and clinical significance of
      high CD86 expression on plasma cells at diagnosis and studied the ability of
      trimeric human CD40 ligand (huCD40LT) to up-regulate the expression of the B7
      family on malignant plasma cells. CD86 expression on plasma cells was increased
      in 54% of the patients studied at diagnosis (n = 35) and was associated with a
      significantly shorter survival (median, 28 versus 57 months; chi(2) = 4.6; P
      =.03) and a higher tumor load (patients with more than 50% bone marrow plasma
      cells, 47% versus 6%; chi(2) = 7.2; P =.005). CD86 expression was highest on
      immature and primitive plasma cells (CD38(++), CD45(+)) of both patients and
      controls and was associated with a CD40(+), CD20(+), CD19(-), CD138(+) phenotype.
      The shortened survival was associated with high CD86 only on mature (CD38(++),
      CD45(-)) plasma cells (chi(2) = 7.6; P =.006). There was no significant
      correlation between high CD86 and other known prognostic markers, including serum
      beta(2)-microglobulin, serum thymidine kinase, and labeling index. The addition
      of huCD40LT to short-term cultures up-regulated both CD80 and CD86 expression on
      B cells (CD19(+)) and CD80 on plasma cells (CD38(++)), but did not up-regulate
      CD86 expression on plasma cells. Thus, B7-2-positive myeloma consists of a
      subgroup of patients with a relatively poor prognosis, and CD40LT may be useful
      in immunotherapy protocols because it up-regulates CD80 expression on malignant
      plasma cells without inducing B7-2-positive myeloma. (Blood. 2000;96:1274-1279)

PMID- 10942369
TI  - Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma:
      a report from the German Hodgkin Lymphoma Study Group.
AB  - To determine prognostic factors and treatment outcome, patients with primary
      progressive Hodgkin lymphoma (HD) registered in the database of the German
      Hodgkin Lymphoma Study Group (GHSG) were analyzed retrospectively. Detailed
      records from randomized prospective multicenter trials performed between 1988 and
      1998 of 3807 patients recruited in these trials were reviewed. The median age of
      the 206 patients available was 34 years (range, 16-71). Fifty-seven patients
      (28%) in intermediate stage and 149 patients (72%) in advanced stage developed
      progressive disease (PD). One hundred and fifty-three patients (74%) were treated
      with salvage chemotherapy, 47 patients (23%) with salvage radiotherapy, and 6
      patients (3%) did not receive any therapy due to rapid PD. Seventy patients (34%)
      were treated with high-dose chemotherapy (HDCT) and autologous stem cell
      transplantation. The 5-year freedom from second failure (FF2F) and overall
      survival (OS) for all patients were 17% and 26%, respectively. The 5-year FF2F
      and OS for patients treated with HDCT were 31% and 43%, respectively. In
      multivariate analysis low Karnofsky performance score at the time of progression
      (P <.0001), age above 50 years (P =.019), and failure to attain a temporary
      remission on first-line treatment (P =.0003) were significant adverse prognostic
      factors for OS. Patients with none of these risk factors had a 5-year OS of 55%
      compared with 0% for patients with all 3 of these unfavorable prognostic factors.
      Although HDCT is a reasonable option for selected patients with primary
      progressive HD, the majority did not receive HDCT. Interestingly, salvage
      radiotherapy gave promising results in patients with localized PD. (Blood.
      2000;96:1280-1286)

PMID- 10942370
TI  - A new morphologic classification system for acute promyelocytic leukemia
      distinguishes cases with underlying PLZF/RARA gene rearrangements.
AB  - Acute promyelocytic leukemia (APL) is typified by the t(15;17) translocation,
      which leads to the formation of the PML/RARA fusion gene and predicts a
      beneficial response to retinoids. However, approximately 10% of all APL cases
      lack the classic t(15;17). This group includes (1) cases with cryptic PML/RARA
      gene rearrangements and t(5;17) that leads to the NPM/RARA fusion gene, which are
      retinoid-responsive, and (2) cases with t(11;17)(q23;q21) that are associated
      with the PLZF/RARA fusion gene, which are retinoid-resistant. A key issue is how
      to rapidly distinguish subtypes of APL that demand distinct treatment approaches.
      To address this issue, a European workshop was held in Monza, Italy, during June
      1997, and a morphologic, immunophenotypic, cytogenetic, and molecular review was
      undertaken in 60 cases of APL lacking t(15;17). This process led to the
      development of a novel morphologic classification system that takes into account
      the major nuclear and cytoplasmic features of APL. There were no major
      differences observed in morphology or immunophenotype between cases with the
      classic t(15;17) and those with the cryptic PML/RARA gene rearrangements. Auer
      rods were absent in the t(5;17) case expressing NPM/RARA. Interestingly, this
      classification system distinguished 9 cases with t(11;17)(q23;q21) and, in
      addition, successfully identified 2 cases lacking t(11;17), which were
      subsequently shown to have underlying PLZF/RARA fusions. The PLZF/RARA cases were
      characterized by a predominance of blasts with regular nuclei, an increased
      number of Pelger-like cells, and by expression of CD56 in 4 of 6 cases tested.
      Use of this classification system, combined with an analysis for CD56 expression,
      should allow early recognition of APL cases requiring tailored molecular
      investigations. (Blood. 2000;96:1287-1296)

PMID- 10942371
TI  - Characterization of acute promyelocytic leukemia cases lacking the classic
      t(15;17): results of the European Working Party. Groupe Francais de Cytogenetique
      Hematologique, Groupe de Francais d'Hematologie Cellulaire, UK Cancer
      Cytogenetics Group and BIOMED 1 European Community-Concerted Action "Molecular
      Cytogenetic Diagnosis in Haematological Malignancies".
AB  - Acute promyelocytic leukemia (APL) is typified by the t(15;17), generating the
      PML-RAR alpha fusion and predicting a beneficial response to retinoids. However,
      a sizeable minority of APL cases lack the classic t(15;17), prompting the
      establishment of the European Working Party to further characterize this group.
      Such cases were referred to a workshop held in Monza, Italy and subjected to
      morphologic, cytogenetic, and molecular review, yielding 60 evaluable patients.
      In the majority (42 of 60), molecular analyses revealed underlying PML/RAR alpha
      rearrangements due to insertions (28 of 42) or more complex mechanisms, including
      3-way and simple variant translocations (14 of 42). Metaphase fluorescence in
      situ hybridization (FISH) demonstrated that insertions most commonly led to
      formation of the PML-RAR alpha fusion gene on 15q. In 11 of 60 workshop patients,
      PLZF/RAR alpha rearrangements were identified, including 2 patients lacking the
      t(11;17)(q23;q21). In one case with a normal karyotype, FISH analysis revealed
      insertion of RAR alpha into 11q23, and PLZF-RAR alpha was the sole fusion gene
      formed. Two patients were found to have t(5;17), one with a diffuse nuclear NPM
      staining pattern and with NPM-RAR alpha and RAR alpha-NPM transcripts detected.
      In the other with an unbalanced der(5)t(5;17)(q13;q21) and a nucleolar NPM
      localization pattern, an NPM/RAR alpha rearrangement was excluded, and FISH
      revealed deletion of one RAR alpha allele. In the remaining 5 workshop patients,
      no evidence was found for a rearrangement of RAR alpha, indicating that in rare
      instances, alternative mechanisms could mediate the differentiation block that
      typifies this disease. This study highlights the importance of combining
      morphologic, cytogenetic, and molecular analyses for optimal management of APL
      patients and better understanding of the pathogenesis of the disease. (Blood.
      2000;96:1297-1308)

PMID- 10942372
TI  - Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory
      proteins.
AB  - Resting lymphocytes are refractory to gene transfer using Moloney murine leukemia
      virus (MMLV)-based retroviral vectors because of their quiescent status.
      Recently, it has been shown that lentiviral vectors are capable of transferring
      genes into nondividing and terminally differentiated cells. We used human
      immunodeficiency virus type-1 (HIV-1)-based vectors expressing enhanced green
      fluorescent protein (EGFP) driven by different promoters (CMV, MPSV, or PGK) and
      investigated their ability to transduce human T- and B-cell lines, as well as
      resting or activated primary peripheral and umbilical cord blood lymphocytes. The
      effects of the presence or the absence of HIV-1 accessory proteins (Vif, Vpr,
      Vpu, and Nef) in the vector system were also assessed. Flow cytometry analysis
      showed no differences in the ability of these vectors of transferring the
      reporter gene into lymphocytic lines and mitogen-stimulated primary lymphocytes
      in the presence or the absence of HIV-1 accessory proteins (APs). Similarly,
      viral supernatants generated in the presence of accessory genes could efficiently
      transduce various subsets of resting lymphocytes and provide long-term expression
      of the transgene. No significant transduction-induced changes in cell activation
      or cycling status were observed and Alu-HIV-1 long terminal repeat polymerase
      chain reaction (LTR PCR) analysis demonstrated integration of the vector
      sequences at the molecular level. In contrast, in the absence of HIV-1 APs,
      lentiviral vectors failed to integrate and express the transgene in resting
      lymphocytes. These results show that transduction of primary resting lymphocytes
      with HIV-1-based vectors requires the presence of viral accessory proteins.
      (Blood. 2000;96:1309-1316)

PMID- 10942373
TI  - Lentiviral vectors for efficient delivery of CD80 and granulocyte-macrophage-
      colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid
      leukemia cells to induce antileukemic immune responses.
AB  - Cell vaccines engineered to express immunomodulators have shown feasibility in
      eliminating leukemia in murine models. Vectors for efficient gene delivery to
      primary human leukemia cells are required to translate this approach to clinical
      trials. In this study, second-generation lentiviral vectors derived from human
      immunodeficiency virus 1 were evaluated, with the cytomegalovirus (CMV) promoter
      driving expression of granulocyte-macrophage-colony-stimulating factor (GM-CSF)
      and CD80 in separate vectors or in a bicistronic vector. The vectors were
      pseudotyped with vesicular stomatitis virus G glycoprotein and concentrated to
      high titers (10(8)-10(9) infective particles/mL). Human acute lymphoblastic
      leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia cell
      lines transduced with the monocistronic pHR-CD80 vector or the bicistronic pHR
      GM/CD vector became 75% to 95% CD80 positive (CD80(+)). More important,
      transduction of primary human ALL and AML blasts with high-titer lentiviral
      vectors was consistently successful (40%-95% CD80(+)). The average amount of GM
      CSF secretion by the leukemia cell lines transduced with the pHR-GM-CSF
      monocistronic vector was 2182.9 pg/10(6) cells per 24 hours. Secretion was
      markedly lower with the bicistronic pHR-GM/CD vector (average, 225.7 pg/10(6)
      cells per 24 hours). Lower amounts of CMV-driven messenger RNA were detected with
      the bicistronic vector, which may account for its poor expression of GM-CSF.
      Primary ALL cells transduced to express CD80 stimulated T-cell proliferation in
      an autologous mixed lymphocyte reaction. This stimulation was specifically
      blocked with monoclonal antibodies reactive against CD80 or by recombinant
      cytotoxic T-lymphocyte antigen 4-immunoglobulin fusion protein. These results
      show the feasibility of efficiently transducing primary leukemia cells with
      lentiviral vectors to express immunomodulators to elicit antileukemic immune
      responses. (Blood. 2000;96:1317-1326)

PMID- 10942374
TI  - Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal
      phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte
      response in vitro.
AB  - Dendritic cells (DCs) genetically modified to continually express and present
      antigens may be potent physiologic adjuvants for induction of prophylactic or
      therapeutic immunity. We have previously shown that an env and nef deleted HIV-1
      vector (HIV-1 delta EN) pseudotyped with VSV-G transduced monocyte-derived
      macrophages as well as CD34(+) precursors of DCs. Here we extended these findings
      with HIV-1 delta EN to highly differentiated human DCs derived in culture from
      circulating monocytes (DCs). In addition, a new vector derived from HIV-1 delta
      EN but further deleted in its remaining accessory genes vif, vpr, and vpu (HIV-1
      delta EN V(3)) was also tested. Both vectors efficiently transduced DCs.
      Transduction of DCs did not significantly alter their viability or their
      immunophenotype when compared with untransduced DCs. Furthermore, the phagocytic
      potential of immature DCs, as well as their ability to differentiate into mature
      DCs capable of stimulating T-cell proliferation, was not affected. Finally, DCs
      transduced by the HIV-1 delta EN vector were able to elicit a primary antiviral
      cytotoxic T-cell response in autologous CD8 T cells. These results suggest that
      HIV-1-based vectors expressing viral antigens may be useful for in vivo active
      immunization as well as ex vivo priming of cytotoxic T cells for adoptive T-cell
      therapy. (Blood. 2000;96:1327-1333)

PMID- 10942375
TI  - Mild preconditioning and low-level engraftment confer methotrexate resistance in
      mice transplanted with marrow expressing drug-resistant dihydrofolate reductase
      activity.
AB  - Effective engraftment of hematopoietic cells targeted for gene transfer is
      facilitated by cytoreductive preconditioning such as high-dose total body
      irradiation (TBI). To minimize the adverse side effects associated with TBI,
      experiments were conducted to determine whether sublethal doses of TBI would
      allow sufficient engraftment of MTX-resistant hematopoietic cells to confer
      survival on recipient mice administered MTX. FVB/N animals were administered 1,
      2, or 4 Gy TBI (lethal dose, 8.5 Gy), transplanted with 10(7) FVB/N transgenic
      marrow cells expressing an MTX-resistant dihydrofolate reductase (DHFR)
      transgene, and then administered MTX daily for 60 days. Control mice administered
      1 Gy with or without subsequent transplantation of normal marrow cells succumbed
      to MTX toxicity by day 45. In contrast, nearly all animals transplanted with
      transgenic marrow survived MTX administration, regardless of the TBI dose used
      for preconditioning. The donor DHFR transgenic marrow engraftment level was
      proportional to the preconditioning dose of TBI but was surprisingly reduced in
      animals given 2 or 4 Gy TBI and subsequently administered MTX when compared with
      control animals administered phosphate-buffered saline. Animals preconditioned
      with 1 Gy were also protected from MTX toxicity when transplanted with reduced
      amounts (5 x 10(6) and 1 x 10(6) cells) of DHFR transgenic donor marrow,
      resulting in low-level (approximately 1%) engraftment. In conclusion, very mild
      preconditioning allows sufficient low-level engraftment of genetically modified
      stem cells for in vivo manifestation of the modified phenotype, suggesting the
      usefulness of mild preconditioning regimens in human gene therapy trials
      targeting hematopoietic stem cells. (Blood. 2000;96:1334-1341)

PMID- 10942376
TI  - Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in
      myelofibrosis.
AB  - Idiopathic myelofibrosis (MF) is a myeloproliferative syndrome characterized by
      an increase in bone marrow collagen. Megakaryocytes (Mks), which store growth
      factors in their alpha granules, are known to be involved in the pathogenesis of
      MF. Previously, mice given bone marrow grafts infected with a retrovirus carrying
      murine thrombopoietin (TPO) complementary DNA developed a disease resembling
      human idiopathic MF. In this study, we used this murine model (TPO mice) to
      determine whether release of alpha granules is responsible for fibroblast
      activation and development of fibrosis. The intracellular trafficking of several
      alpha-granule proteins (von Willebrand factor, fibrinogen, and transforming
      growth factor beta (TGF beta), which are stored in the granule matrix; and
      alpha(IIb)beta(3) integrin and P-selectin (CD62p), which are located in the alpha
      granule membrane) was studied with immune electron microscopy in bone marrow Mks
      from TPO mice. P-selectin immunolabeling increased consistently and was
      occasionally found lining the demarcation membrane system. Evidence of extensive
      emperipolesis was also found in TPO mouse Mks, involving almost exclusively
      neutrophil and eosinophil polymorphonuclear (PMN) cells with altered morphologic
      features. In parallel, the host Mks had myeloperoxidase-positive granules
      scattered in their cytoplasm, associated with marked ultrastructural cytoplasmic
      alterations and ruptured alpha-granule membranes. Similar observations were made
      in bone marrow biopsy specimens from 12 patients with idiopathic MF; indeed,
      there was an increased rate of emperipolesis involving mostly PMN cells, abnormal
      P-selectin expression, and mutual subcellular PMN and Mk alterations. This study
      indicates that in idiopathic MF, abnormal P-selectin distribution in Mks induces
      selective sequestration of PMN cells. This results in a release of alpha-granular
      proteins and growth factors, which in turn induces fibroblast activation and
      fibrosis deposition. (Blood. 2000;96:1342-1347)

PMID- 10942377
TI  - Identification of a GATA-overlapping sequence within the enhancer of the murine
      GPIIb promoter that induces transcriptional deregulation in human K562 cells.
AB  - The human and the murine glycoprotein platelet IIb (GPIIb) promoters are
      megakaryocyte specific in human and murine cell systems, respectively. Here we
      show that the murine promoter is, however, highly active when transfected in K562
      human cells in which the human promoter is almost inactive. A murine promoter, in
      which the enhancer element was replaced by the human, retrieves its
      megakaryocytic specificity in human cell lines. The human and murine GATA-binding
      sites located in the enhancer region display slight sequence divergence next to
      the consensus GATA core sequence. Gel shift experiments show that, although the
      murine and the human GATA sequences both bind GATA-1, the murine sequence alone
      forms an additional complex (B) not detected with the human sequence. When the
      murine GATA-containing region is replaced by the human in the context of the
      murine GPIIb promoter, megakaryocyte specificity is restored in the human cell
      lines. A G nucleotide 3 to GATA appears crucial because its substitution
      abrogates B but not GATA-1 binding and restores megakaryocyte specificity to the
      murine promoter. Conversely, substitution of the human GATA-1 binding sequence by
      its murine homologue that binds both GATA-1 and complex B induces an abnormal
      activity for the human promoter in K562 cells. Altogether, our data suggest that
      limited changes in the GATA-containing enhancer of the GPIIb promoter can induce
      the recruitment of accessory proteins that could be involved in alteration of a
      megakaryocyte-restricted gene activation program. (Blood. 2000;96:1348-1357)

PMID- 10942379
TI  - Hematopoietic-specific beta 1 tubulin participates in a pathway of platelet
      biogenesis dependent on the transcription factor NF-E2.
AB  - The cellular and molecular bases of platelet release by terminally differentiated
      megakaryocytes represent important questions in cell biology and hematopoiesis.
      Mice lacking the transcription factor NF-E2 show profound thrombocytopenia, and
      their megakaryocytes fail to produce proplatelets, the microtubule-based
      precursors of blood platelets. Using mRNA subtraction between normal and NF-E2
      deficient megakaryocytes, cDNA was isolated encoding beta1 tubulin, the most
      divergent beta tubulin isoform. In NF-E2-deficient megakaryocytes, beta1 tubulin
      mRNA and protein are virtually absent. The expression of beta1 tubulin is
      exquisitely restricted to platelets and megakaryocytes, where it appears late in
      differentiation and localizes to microtubule shafts and coils within
      proplatelets. Restoring NF-E2 activity in a megakaryoblastic cell line or in NF
      E2-deficient primary megakaryocytes rescues the expression of beta1 tubulin. Re
      expressing beta1 tubulin in isolation does not, however, restore proplatelet
      formation in the defective megakaryocytes, indicating that other critical factors
      are required; indeed, other genes identified by mRNA subtraction also encode
      structural and regulatory components of the cytoskeleton. These findings provide
      critical mechanistic links between NF-E2, platelet formation, and selected
      microtubule proteins, and they also provide novel molecular insights into
      thrombopoiesis. (Blood. 2000;96:1366-1373)

PMID- 10942378
TI  - Myeloid differentiation of FdCP1 cells is dependent on Stat5 processing.
AB  - The IL-3 family of cytokines transduces signals through Stat5 and regulates
      myeloid development. Previous studies have determined that a carboxy terminally
      truncated isoform of Stat5 is activated in immature myeloid cells. This isoform,
      which lacks a transcriptional activation domain, is generated by a protein
      processing event. To determine whether Stat5 cleavage plays an important role in
      the growth and maturation of myeloid progenitors, the FdCP1 model of myeloid
      maturation was evaluated. FdCP1 cells are IL-3-dependent myeloid progenitors that
      differentiate into monocytes when cultured in granulocyte macrophage-colony
      stimulating factor (GM-CSF). Consistent with their immature phenotype, when FdCP1
      cells are cultured in IL-3 they exhibit robust protease activity and signal
      through truncated Stat5 isoforms. In contrast, maturation leads to a loss of
      protease activity and a switch to the expression to full-length Stat5 isoforms.
      Introduction of a noncleavable, full-length Stat5 mutant into undifferentiated
      FdCP1 cells leads to a partially differentiated phenotype and prevents further
      differentiation in response to GM-CSF. These results support our hypothesis that
      Stat5 processing is important for myeloid maturation. (Blood. 2000;96:1358-1365)

PMID- 10942380
TI  - Distinct functional properties of highly purified hematopoietic stem cells from
      mouse strains differing in stem cell numbers.
AB  - We have previously demonstrated that young adult DBA/2 (DBA) mice have more stem
      cells than C57BL/6 (B6) mice, as measured in a cobblestone area-forming cell
      (CAFC) assay using unfractionated marrow. To study the nature of this difference,
      we have now compared the proliferative fate of single, highly enriched Sca-1(+)c
      kit(+)Lin(-) stem cells from these strains. Although equal in frequency,
      functional comparison revealed that Sca-1(+)c-kit(+)Lin(-) cells from DBA mice
      contained twice as many cells with CAFC activity. DBA clones persisted much
      longer in vitro, and developed later in time. To assess whether these differences
      were of any functional relevance in vivo, we compared engraftment of lethally
      irradiated mice transplanted with 1000 B6 or DBA Sca-1(+)c-kit(+)Lin(-) cells.
      Recipients of enriched DBA cells recovered much faster than animals transplanted
      with B6 cells. We also studied endogenous hematopoietic recovery after 5
      fluorouracil (5-FU) treatment in vivo. Progenitors and peripheral blood cells
      recovered twice as fast in DBA mice. Thus, DBA stem cells have superior
      proliferative potential compared with phenotypically identical stem cells
      obtained from B6 mice. Such genetically determined quantitative and qualitative
      differences in stem cell behavior likely contribute to the dramatically different
      hematopoietic recovery rates observed in human transplant patients. (Blood.
      2000;96:1374-1379)

PMID- 10942381
TI  - Homing and engraftment potential of Sca-1(+)lin(-) cells fractionated on the
      basis of adhesion molecule expression and position in cell cycle.
AB  - Engraftment potential of hematopoietic stem cells (HSCs) is likely to be
      dependent on several factors including expression of certain adhesion molecules
      (AMs) and degree of mitotic quiescence. The authors investigated the functional
      properties and engraftment potential of Sca-1(+)lin(-) cells subfractionated on
      the basis of expression, or lack thereof, of CD11a, CD43, CD49d, CD49e, or CD62L
      and correlated that expression with cell cycle status and proliferative potential
      of engrafting fractions. Donor-derived chimerism in mice receiving CD49e(+) or
      CD43(+) Sca-1(+)lin(-) cells was greater than that in mice receiving cells
      lacking these 2 markers, while Sca-1(+)lin(-) cells positive for CD11a and CD62L
      and bright for CD49d expression mediated minimal engraftment. AM phenotypes
      enriched for engraftment potential contained the majority of high proliferative
      potential-colony forming cells, low proliferative potential-colony forming cells,
      and cells providing rapid in vitro expansion. Cell cycle analysis of AM
      subpopulations revealed that, regardless of their bone marrow repopulating
      potential, Sca-1(+)lin(-) AM(-) cells contained a higher percentage of cells in
      G(0)/G(1) than their AM(+) counterparts. Interestingly, engrafting phenotypes,
      regardless of the status of their AM expression, were quicker to exit G(0)/G(1)
      following in vitro cytokine stimulation than their opposing phenotypes. When
      engrafting phenotypes of Sca-1(+)lin(-) AM(+) or AM(-) cells were further
      fractionated by Hoechst 33342 into G(0)/G(1) or S/G(2)+M, cells providing long
      term engraftment were predominantly contained within the quiescent fraction.
      These results define a theoretical phenotype of a Sca-1(+)lin(-) engrafting cell
      as one that is mitotically quiescent, CD43(+), CD49e(+), CD11a(-), CD49d(dim),
      and CD62L(-). Furthermore, these data suggest that kinetics of in vitro
      proliferation may be a good predictor of engraftment potential of candidate
      populations of HSCs. (Blood. 2000;96:1380-1387)

PMID- 10942382
TI  - Intramedullary apoptosis of hematopoietic cells in myelodysplastic syndrome
      patients can be massive: apoptotic cells recovered from high-density fraction of
      bone marrow aspirates.
AB  - A higher percentage of apoptotic cells (apoptotic index or AI) is consistently
      found in bone marrow (BM) biopsies compared to BM aspirates of patients with
      myelodysplastic syndrome (MDS). Most studies have only investigated the low
      density fraction (LDF) mononuclear cells from BM aspirates following density
      separation for AI determination. In the present study, both LDF and high-density
      fraction (HDF) cells for AI were examined by electron microscopy (EM) in 10 MDS
      patients and 4 healthy donors. Matched BM biopsies were subjected to AI detection
      by in situ end labeling (ISEL) of fragmented DNA. The results indicate that in
      LDF and HDF cells, AI is consistently higher in MDS patients (8.5% vs 1.5%,
      respectively; P =.039) compared to healthy donors (27% vs 4%, respectively; P =.
      004). The BM biopsy AI was also higher in MDS patients than in healthy donors (3+
      vs 0+, respectively; P =.036). In addition, in MDS patients, more apoptotic cells
      were found in HDF cells than in LDF cells (27% vs 8.5%, respectively;P =.0001).
      All stages of maturation, ranging from blasts to terminally mature cells
      belonging to all 3 lineages, were represented in the dying cells in both
      compartments. Using EM, typical Pelger-Huett-type cells appeared to be apoptotic
      granulocytes. Both LDF and HDF cells should be examined for an accurate
      estimation of apoptotic cells because AI would be underestimated if only the LDF
      cells were studied. Ultrastructural studies consistently show a higher AI in BM
      biopsies compared to BM aspirates despite the correction factor of HDF cells
      provided by AI. This may represent the actual extant state, which could
      conceivably be due to a higher concentration of proapoptotic signals in the
      biopsies. (Blood. 2000;96:1388-1392)

PMID- 10942384
TI  - Thrombasthenic mice generated by replacement of the integrin alpha(IIb) gene:
      demonstration that transcriptional activation of this megakaryocytic locus
      precedes lineage commitment.
AB  - To analyze the transcriptional activity of the gene encoding the alpha subunit of
      the platelet integrin alpha(IIb)beta(3) during the hematopoietic differentiation,
      mice were produced in which the herpes virus thymidine kinase (tk) was introduced
      in this megakaryocytic specific locus using homologous recombination technology.
      This provided a convenient manner in which to induce the eradication of
      particular hematopoietic cells expressing the targeted gene. Results of
      progenitor cell cultures and long-term bone marrow (BM) assays showed that the
      growth of a subset of stem cells was reduced in the presence of the antiherpetic
      drug ganciclovir, demonstrating that the activation of the toxic gene occurs
      before the commitment to the megakaryocytic lineage. Furthermore the knock-in of
      the tk gene into the alpha(IIb) locus resulted in the knock-out of the alpha(IIb
      )gene in homozygous mice. Cultures of BM cells of these animals, combined with
      ultrastructural analysis, established that the alpha(IIb) glycoprotein is
      dispensable for lineage commitment and megakaryocytic maturation. Platelets
      collected from alpha(IIb)-deficient mice failed to bind fibrinogen, to aggregate,
      and to retract a fibrin clot. Moreover, platelet alpha-granules did not contain
      fibrinogen. Consistent with these characteristics, the mice displayed bleeding
      disorders similar to those in humans with Glanzmann thrombasthenia. (Blood.
      2000;96:1399-1408)

PMID- 10942383
TI  - The alpha-defensins stimulate proteoglycan-dependent catabolism of low-density
      lipoprotein by vascular cells: a new class of inflammatory apolipoprotein and a
      possible contributor to atherogenesis.
AB  - Inflammation may contribute to the pathogenesis of atherosclerosis. On the basis
      of previous reports that human atherosclerotic lesions contain alpha-defensins, a
      class of cationic proteins released by activated neutrophils, the study was
      designed to ask whether defensins modulate the binding and catabolism of low
      density lipoprotein (LDL) by human vascular cells. The results of the study
      demonstrated that defensin stimulated the binding of (125)I-LDL to cultured human
      umbilical vein endothelial cells, smooth muscle cells, and fibroblasts
      approximately 5-fold in a dose-dependent and saturable manner. Defensin and LDL
      formed stable complexes in solution and on cell surfaces. Stimulation of LDL
      binding by defensin was not inhibited by antibodies against the LDL-receptor (LDL
      R), or by recombinant receptor-associated protein, which blocks binding of
      ligands to the alpha(2)-macroglobulin receptor/LDL-R-related protein and other
      LDL-R family members. Furthermore, defensin stimulated the binding, endocytosis,
      and degradation of LDL by fibroblasts lacking LDL-R. Stimulation of LDL
      degradation by defensin was inhibited approximately 75% by low concentrations of
      heparin (0.2 units/mL) and was similarly reduced in CHO cells lacking heparan
      sulfate-containing proteoglycans. The effect of defensin was substantially
      increased in cells overexpressing the core protein of the syndecan-1 heparan
      sulfate proteoglycan. The alpha-defensins released from activated neutrophils may
      provide a link between inflammation and atherosclerosis by changing the pattern
      of LDL catabolism from LDL-R to the less efficient LDL-R-independent,
      proteoglycan-dependent pathway. (Blood. 2000;96:1393-1398)

PMID- 10942385
TI  - Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a target glycoprotein
      in drug-induced thrombocytopenia.
AB  - Drug-induced immune thrombocytopenia (DITP) is a serious complication of drug
      treatment. Previous studies demonstrated that most drug-dependent antibodies
      (DDAbs) react with the platelet membrane glycoprotein (GP) complexes IIb/IIIa and
      Ib/IX/V. We analyzed the sera from 5 patients who presented with DITP after
      intake of carbimazole. Notably, thrombocytopenia induced by carbimazole was
      relatively mild in comparison to patients with DITP induced by quinidine. The
      sera reacted with platelets in an immunoassay on addition of the drug. In
      immunoprecipitation experiments with biotin-labeled platelets and endothelial
      cells, reactivity with the platelet endothelial cell adhesion molecule-1 (PECAM
      1, CD31) could be demonstrated, whereas neither GPIIb/IIIa nor GPIb/IX was
      precipitated in the presence of the drug. These results could be confirmed by GP
      specific immunoassay (MAIPA) using monoclonal antibodies (mabs) against PECAM-1.
      In addition, the binding of DDAbs could be abolished by preincubation with
      soluble recombinant PECAM-1. Carbimazole-dependent antibodies showed similar
      reactivity with platelets carrying the Leu(125) and Val(125) PECAM-1 isoforms,
      indicating that this polymorphic structure, which is located in the first
      extracellular domain, is not responsible for the epitope formation. Binding
      studies with biotin-labeled mutants of PECAM-1 and analysis of sera with mabs
      against different epitopes on PECAM-1 in MAIPA assay suggested that carbimazole
      dependent antibodies prominently bound to the second immunoglobulin homology
      domain of the molecule. Analysis of 20 sera from patients with quinidine-induced
      thrombocytopenia by MAIPA assay revealed evidence that DDAbs against PECAM-1 are
      involved in addition to anti-GPIb/IX and anti-GPIIb/IIIa. We conclude that PECAM
      1 is an important target GP in DITP. (Blood. 2000;96:1409-1414)

PMID- 10942386
TI  - The cJun N-terminal kinase (JNK) signaling pathway mediates induction of
      urokinase-type plasminogen activator (uPA) by the alkylating agent MNNG.
AB  - The monofunctional alkylating agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) is
      a widespread environmental carcinogen that causes DNA lesions, leading to cell
      death. However, MNNG can also trigger a cell-protective response by inducing the
      expression of DNA repair/transcription-related genes. We demonstrate that the
      urokinase-type plasminogen activator (uPA) gene product, a broad spectrum
      extracellular protease to which no DNA repair function has been assigned, is
      transcriptionally induced by MNNG in C2C12 and NIH3T3 cells. This induction
      required an AP1-enhancer element located at -2.4 kilobase (kb), because it was
      abrogated by deletion of this site. MNNG was found to induce the activation of
      JNK/SAPK and p38 mitogen-activated protein kinases (MAPKs). Accordingly, we
      attempted to assess the contribution of each of these MNNG-inducible MAPKs to uPA
      gene induction by this alkylating agent. Coexpression of dominant negative
      versions of kinases of the JNK pathway, such as catalytically inactive forms of
      MEKK1, MKK7, and JNKK, and of cytoplasmic JNK-inhibitor JIP-1, as well as
      treatment of cells with curcumin (which blocks JNK activation by MNNG), inhibited
      MNNG-induced uPA transcriptional activity. In contrast, neither dominant negative
      MKK6 nor SB203580, which specifically inhibit p38 MAP kinase activation,
      abrogated the MNNG-induced effect. Taken together, our results show that the JNK
      signaling pathway links external MNNG stimulation and AP1-dependent uPA gene
      expression, providing the first functional dissection of a transcription-coupled
      signal transduction pathway for MNNG. (Blood. 2000;96:1415-1424)

PMID- 10942387
TI  - Recombinant staphylokinase variants with reduced antigenicity due to elimination
      of B-lymphocyte epitopes.
AB  - Site directed mutagenesis (350 variants) of recombinant staphylokinase (SakSTAR),
      a potent fibrin-selective thrombolytic agent, was undertaken in order to reduce
      its antigenicity while maintaining its potency. Variants with K35A, (ie, Lys[K]
      in position 35 substituted with Ala[A]), E65D or E65Q, K74R or K74Q, E80A+D82A,
      K130T, and K135R displayed increased enzymatic activity or reduced binding of
      human staphylokinase-specific antibodies. Additive mutagenesis identified 8
      variants with intact thrombolytic potencies, which absorbed down to less than a
      third of SakSTAR-specific antibodies. Intra-arterial administration in 61
      patients with peripheral arterial occlusion caused no significant allergic
      reactions. Median neutralizing antibody titers (with 15 to 85 percentiles),
      expressed as microgram (microg) compound neutralized per milliliter plasma, were
      4.4 (0.3 to 49) for the variants, compared with 12 (4 to 100) in 70 patients
      given wild-type SakSTAR (P =.002 by Mann-Whitney rank sum test). Overt
      neutralizing antibody induction (more than 5 microg compound neutralized per
      milliliter plasma) was observed in 57 of 70 patients (81%) given wild-type
      SakSTAR, but only in 28 of 60 patients (47%) treated with variants (P <.0001 by
      Fisher exact test). On the basis of this study, the variant SakSTAR (K35A, E65Q,
      K74R, D82A, S84A, T90A, E99D, T101S, E108A, K109A, K130T, K135R) (code SY155) has
      been selected for further clinical development. (Blood. 2000;96:1425-1432)

PMID- 10942388
TI  - Platelet adhesion to collagen in healthy volunteers is influenced by variation of
      both alpha(2)beta(1) density and von Willebrand factor.
AB  - Platelet thrombus formation on collagen is initiated by platelet GPIb interaction
      with von Willebrand factor (vWF) bound to collagen, followed by firm attachment
      of the platelet to collagen by the integrin alpha(2)beta(1). Platelet and plasma
      vWF levels and alpha(2)beta(1) density on the platelet surface are highly
      variable among normal subjects; however, little is known about the consequences
      of this variability on platelet adhesion to collagen. A population of 32 normal
      subjects was studied to evaluate the relation between genetic and phenotypic
      variations of alpha(2)beta(1) density on the platelet surface, plasma vWF levels,
      platelet vWF levels, and adenosine diphosphate and adenosine triphosphate
      concentrations on the one hand and platelet adhesion to collagen under flow on
      the other hand. Platelet adhesion to collagen types I and III under flow was
      correlated with plasma levels of vWF (r(2) = 0.45 and 0.42, respectively) and
      alpha(2)beta(1) density on the platelet surface (r(2) = 0.35 and 0.17, not
      significant). Platelet adhesion to collagen type IV under flow was significantly
      correlated with platelet vWF levels (r(2) = 0.34) and alpha(2)beta(1) density on
      the platelet surface (r(2) = 0.42). Platelet adhesion to collagen types I and III
      depends on both plasma levels of vWF and alpha(2)beta(1) density on the platelet
      surface, whereas platelet adhesion to collagen type IV is mediated by both
      platelet vWF levels and alpha(2)beta(1) density on the platelet surface. (Blood.
      2000;96:1433-1437)

PMID- 10942389
TI  - HIV-1 gp120- and gp160-induced apoptosis in cultured endothelial cells is
      mediated by caspases.
AB  - The immune dysfunction and cell destruction that occur in the human
      immunodeficiency virus (HIV)-infected host appear to result from the direct
      cytopathic effects of viral infection and the effects of viral proteins on
      uninfected bystander cells. Recently, the alpha-chemokine receptor CXCR4 has been
      reported to mediate apoptosis in neuronal cells and in CD4(+) and CD8(+) T cells
      after its binding to HIV-1 envelope proteins. In the current study, it was
      observed that human umbilical vein endothelial cells (HUVEC) undergo apoptosis
      after their treatment with the HIV-1 envelope proteins gp120/160. Anti-CXCR4
      monoclonal antibody decreased HIV-1 gp120/160-induced apoptosis, suggesting that
      the CXCR4 chemokine receptor mediates the apoptotic effects of these HIV envelope
      glycoproteins. Further studies revealed that caspases play an important role in
      this process because the pretreatment of cells with a general caspase enzyme
      inhibitor decreased the extent of HUVEC apoptosis induced by gp120/160. In
      addition, it was found that caspase-3 was activated on HIV-1 gp120/160 treatment
      of these cells. It was also observed that gp120/160 treatment slightly increased
      the expression of the pro-apoptotic molecule Bax. These results suggest that HIV
      1 envelope glycoproteins can disrupt endothelial integrity through the
      interaction with CXCR4, thereby facilitating virus transit out of the bloodstream
      and contributing to the vascular injury syndromes seen in acquired
      immunodeficiency syndrome. (Blood. 2000;96:1438-1442)

PMID- 10942390
TI  - Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A)
      affecting the prothrombinase complex in a thrombophilic family.
AB  - The study of the molecular bases of thrombophilia in a large family with 4
      symptomatic members is reported. Three thrombophilic genetic components (FV
      R506Q, FV H1299R, and PT 20210G/A), all affecting the activity of the
      prothrombinase complex, were detected alone and in combination in various family
      members. In addition, a newly identified missense mutation (factor V [FV]
      Y1702C), causing FV deficiency, was also present in the family and appeared to
      enhance activated protein C (APC) resistance in carriers of FV R506Q or FV H1299R
      by abolishing the expression of the counterpart FV allele. The relationships
      between complex genotypes, coagulation laboratory findings, and clinical
      phenotypes were analyzed in the family. All symptomatic family members were
      carriers of combined defects and showed APC resistance and elevated F1 + 2
      values. Evidence for the causative role of the FV Y1702C mutation, which affects
      a residue absolutely conserved in all 3 A domains of FV, factor VIII, and
      ceruloplasmin, relies on (1) the absolute cosegregation between the mutation and
      FV deficiency, both in the family and in the general population; (2) FV antigen
      and immunoblot studies indicating the absence of Y1702C FV molecules in plasma of
      carriers of the mutation, despite normal levels of the FV Y1702C messenger RNA;
      and (3) molecular modeling data that support a crucial role of the mutated
      residue in the A domain structure. These findings help to interpret the variable
      penetrance of thrombosis in thrombophilic families and to define the molecular
      bases of FV deficiency. (Blood. 2000;96:1443-1448)

PMID- 10942391
TI  - SHIP inhibits Akt activation in B cells through regulation of Akt membrane
      localization.
AB  - Activation of the serine/threonine kinase Akt and the regulation of its
      activation are recognized as critical in controlling proliferative/survival
      signals via many hematopoietic receptors. In B lymphocytes, the B-cell receptor
      (BCR)-mediated activation of Akt is attenuated by co-cross-linking of BCR with
      the inhibitory receptor Fc gamma RIIB1, and the binding of the SH2 domain
      containing inositol phosphatase, SHIP, to Fc gamma RIIB1. Because SHIP
      dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3) and activation
      of Akt requires PIP3, the destruction of this phospholipid has been proposed as
      the mechanism for Akt inhibition. However, upstream kinases that activate Akt,
      such as PDK1, also require PIP3 for activation. In this report, we addressed
      whether SHIP inhibits Akt directly at the level of Akt recruitment to the
      membrane, indirectly through PDK recruitment/phosphorylation of Akt, or both. We
      generated stable B-cell lines expressing a regulatable, but constitutively
      membrane-bound Akt that still required PDK-dependent phosphorylation for
      activation. Several lines of evidence suggested that activation of this membrane
      targeted Akt is not inhibited by Fc gamma RIIB1/SHIP and that PDK is not a target
      for SHIP-mediated inhibition. These data demonstrate that SHIP inhibits Akt
      primarily through regulation of Akt membrane localization. We also observed
      during these studies that Fc gamma RIIB1/SHIP does not inhibit p70(S6k)
      activation, even though several other PIP3-dependent events were down-regulated.
      Because the enhanced activation of Akt in the absence of SHIP correlates with
      hyperproliferation in the myeloid lineage, our data have implications for SHIP
      and Akt-dependent regulation of proliferation in the hematopoietic lineage.
      (Blood. 2000;96:1449-1456)

PMID- 10942392
TI  - Cloning of human early B-cell factor and identification of target genes suggest a
      conserved role in B-cell development in man and mouse.
AB  - Early B-cell factor (EBF) is a helix-loop-helix transcription factor suggested to
      be essential for B-cell development in the mouse. Several genetic targets for EBF
      have been identified in mice, among these the surrogate light chain lambda5 and
      the signal-transducing molecules Igalpha (mb-1) and Igbeta (B29). This article
      reports cloning of the human homologue of EBF, hEBF. This protein has 93%
      sequence and 98.8% amino acid homology with mouse EBF. The encoded protein binds
      DNA and is expressed in cells of the B lineage, but not in cell populations
      representing T lymphocytes or myeloid cells. It is also shown that EBF-binding
      sites are functionally conserved in the human mb-1 and B29 promoters because hEBF
      interacts with these in the electrophoretic mobility shift assay (EMSA) and have
      the ability to increase the activity of reporter constructs under the control of
      these promoters in nonlymphoid HeLa cells. A third genetic target for hEBF is the
      promoter of the human surrogate light chain 14.1. This promoter contains 5
      independent binding sites capable of interacting with hEBF in the EMSA, and the
      activity of the promoter was induced 24-fold in co-transfection experiments.
      These findings suggest that the human homologue of mouse EBF displays conserved
      biochemical features as well as genetic targets, indicating that this protein
      also has an important role in human B-cell development. (Blood. 2000;96:1457
      1464)

PMID- 10942393
TI  - Coadministration of interleukin-18 and interleukin-12 induces a fatal
      inflammatory response in mice: critical role of natural killer cell interferon
      gamma production and STAT-mediated signal transduction.
AB  - The administration of therapeutic doses of recombinant cytokines to patients with
      malignant disease can be complicated by systemic toxicities, which in their most
      severe form may present as a systemic inflammatory response. The combination of
      interleukin (IL)-18 and IL-12 has synergistic antitumor activity in vivo yet has
      been associated with significant toxicity. The effects of IL-18 plus IL-12 were
      examined in a murine model, and it was found that the daily, simultaneous
      administration of IL-18 and IL-12 resulted in systemic inflammation and 100%
      mortality within 4 to 8 days depending on the strain employed. Mice treated with
      IL-18 plus IL-12 exhibited unique pathologic findings as well as elevated serum
      levels of proinflammatory cytokines and acute-phase reactants. The actions of
      tumor necrosis factor-alpha did not contribute to the observed toxicity, nor did
      T or B cells. However, toxicity and death from treatment with IL-18 plus IL-12
      could be completely abrogated by elimination of natural killer (NK) cells or
      macrophages. Subsequent studies in genetically altered mice revealed that NK-cell
      interferon-gamma mediated the fatal toxicity via the signal transducer and
      activator of transcription pathway of signal transduction. These data may provide
      insights into methods of ameliorating cytokine-induced shock in humans. (Blood.
      2000;96:1465-1473)

PMID- 10942394
TI  - Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell
      associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected
      rhesus monkeys.
AB  - Major histocompatibility class I-peptide tetramer technology and simian
      immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys were used to
      clarify the distribution of acquired immunodeficiency syndrome virus-specific
      cytotoxic T lymphocytes (CTL) in secondary lymphoid organs and to assess the
      relationship between these CTL and the extent of viral replication in the various
      anatomic compartments. SIVmac Gag epitope-specific CD8(+) T cells were evaluated
      in the spleen, bone marrow, tonsils, thymus, and 5 different lymph node
      compartments of 4 SIVmac-infected rhesus monkeys. The average percentage of
      CD8(+) T lymphocytes that bound this tetramer in all the different lymph node
      compartments was similar to that in peripheral blood lymphocytes in individual
      monkeys. The percentage of CD8(+) T cells that bound the tetramer in the thymus
      was uniformly low in the monkeys. However, the percentage of CD8(+) T cells that
      bound the tetramer in bone marrow and spleen was consistently higher than that
      seen in lymph nodes and peripheral blood. The phenotypic profile of the tetramer
      binding CD8(+) T lymphocytes in the different lymphoid compartments was similar,
      showing a high expression of activation-associated adhesion molecules and a low
      level expression of naive T-cell-associated molecules. Surprisingly, no
      correlation was evident between the percentage of tetramer-binding CD8(+) T
      lymphocytes and the magnitude of the cell-associated SIV RNA level in each
      lymphoid compartment of individual monkeys. These studies suggest that a dynamic
      process of trafficking may obscure the tendency of CTL to localize in particular
      regional lymph nodes or that some lymphoid organs may provide milieus that are
      particularly conducive to CTL expansion. (Blood. 2000;96:1474-1479)

PMID- 10942395
TI  - Immunity to WT1 in the animal model and in patients with acute myeloid leukemia.
AB  - The Wilms' tumor (WT1) gene participates in leukemogenesis and is overexpressed
      in most types of leukemia in humans. WT1 is also detectable in many types of
      lung, thyroid, breast, testicular, and ovarian cancers and melanoma in humans.
      Initial studies evaluated whether immune responses to murine WT1 can be elicited
      in mice. Murine and human WT1 are similar. Thus, mouse models might lead to
      resolution of many of the critical issues for developing WT1 vaccines. C57/BL6
      (B6) mice were injected with synthetic peptides from the natural sequence of WT1
      containing motifs for binding to major histocompatibility (MHC) class II
      molecules. Immunization induced helper T-cell responses specific for the
      immunizing WT1 peptides and antibody responses specific for WT1 protein.
      Screening of multiple murine cancer cell lines identified 2 murine cancers, TRAMP
      C and BLKSV40, that "naturally" overexpress WT1. Immunization with MHC class I
      binding peptides induced WT1 peptide-specific cytotoxic T-lymphocyte (CTL) that
      specifically lysed TRAMP-C and BLKSV40. WT1 specificity of lysis was confirmed by
      cold target inhibition. No toxicity was noted by histopathologic evaluation in
      the WT1 peptide-immunized animals. WT1 peptide immunization did not show any
      effect on TRAMP-C tumor growth in vivo. Immunization of B6 mice to syngeneic
      TRAMP-C elicited WT1-specific antibody, demonstrating that WT1 can be immunogenic
      in the context of cancer cells. To evaluate whether WT1 might be similarly
      immunogenic in humans, serum from patients with leukemia was evaluated for pre
      existing antibody responses. Western blot analyses showed WT1-specific antibodies
      directed against the N-terminus portion of the WT1 protein in the sera of 3 of 18
      patients with acute myeloid leukemia (AML). (Blood. 2000;96:1480-1489)

PMID- 10942396
TI  - Histone deacetylase inhibitors suppress IL-2-mediated gene expression prior to
      induction of apoptosis.
AB  - Histone deacetylase (HDAC) inhibitors can induce transcriptional activation of a
      number of genes and induce cellular differentiation as histone acetylation levels
      increase. Although these inhibitors induce apoptosis in several cell lines, the
      precise mechanism by which they do so remains obscure. This study shows that HDAC
      inhibitors, sodium butyrate and trichostatin A (TSA), abrogate interleukin (IL)-2
      mediated gene expression in IL-2-dependent cells. The HDAC inhibitors readily
      induced apoptosis in IL-2-dependent ILT-Mat cells and BAF-B03 transfectants
      expressing the IL-2 receptor betac chain, whereas they induced far less apoptosis
      in cytokine-independent K562 cells. However, these inhibitors similarly increased
      acetylation levels of histones in both cells. Although histone hyperacetylation
      is believed to lead to transcriptional activation, the results showed an
      abrogation of IL-2-mediated induction of c-myc, bag-1, and LC-PTP gene
      expression. This observed abrogation of gene expression occurred prior to
      phosphatidylserine externalization, a process that occurs in early apoptotic
      cells. Considering the biologic role played by IL-2-mediated gene expression in
      cell survival, these data suggest that its abrogation may contribute to the
      apoptotic process induced by HDAC inhibitors. (Blood. 2000;96:1490-1495)

PMID- 10942398
TI  - High incidence of chromosome 13 deletion in multiple myeloma detected by
      multiprobe interphase FISH.
AB  - Multiple myeloma (MM) is a hypoproliferative malignancy yielding informative
      karyotypes in no more than 30% of newly diagnosed cases. Although cytogenetic and
      molecular deletion of chromosome 13 is associated with poor prognosis, a MM tumor
      suppressor gene (TSG) has not been identified. To localize a minimal deleted
      region of chromosome 13, clonotypic plasma cells from 50 consecutive patients
      with MM were subjected to interphase fluorescence in situ hybridization (FISH)
      analysis using a panel of 11 probes spanning the entire long arm of chromosome
      13. Whereas chromosome 13 abnormalities were absent in plasma cells from 25
      normal donors, 86% of patients with MM demonstrated such aberrations.
      Heterogeneity, both in deletion frequency and extent, was confirmed by
      simultaneous FISH with 2 chromosome 13 probes. Deletion hot spots were noted at
      D13S272 (70%) and D13S31 (64%), 2 unlinked loci at 13q14. Homozygous deletions at
      these loci occurred in 12% (simultaneously in 8%) of the cases. Molecular
      deletions were found in all 14 patients with morphologic deletions, in 21 of 24
      with uninformative karyotypes, and 8 of 12 patients with karyotype abnormalities
      lacking chromosome 13 deletion. Homozygous deletion of any marker was noted in 4%
      with low and in 36% with higher plasma cell labeling index greater than 0. 4% (P
      =.01). The absence of increasing deletion incidence and extent with therapy
      duration suggests that the observed lesions are not induced by treatment. The
      high incidence and extent of chromosome 13 deletions require the correlation of
      specific deletion(s) with poor prognosis. These analyses will provide valuable
      guidance toward cloning of an MM-TSG. (Blood. 2000;96:1505-1511)

PMID- 10942397
TI  - Gene expression networks underlying retinoic acid-induced differentiation of
      acute promyelocytic leukemia cells.
AB  - To elucidate the molecular mechanism of all-trans-retinoic acid (ATRA)-induced
      differentiation of acute promyelocytic leukemia (APL) cells, the gene expression
      patterns in the APL cell line NB(4) before and after ATRA treatment were analyzed
      using complementary DNA array, suppression-subtractive hybridization, and
      differential-display-polymerase chain reaction. A total of 169 genes, including 8
      novel ones, were modulated by ATRA. The ATRA-induced gene expression profiles
      were in high accord with the differentiation and proliferation status of the
      NB(4) cells. The time courses of their modulation were interesting. Among the 100
      up-regulated genes, the induction of expression occurred most frequently 12-48
      hours after ATRA treatment, while 59 of 69 down-regulated genes found their
      expression suppressed within 8 hours. The transcriptional regulation of 8 induced
      and 24 repressed genes was not blocked by cycloheximide, which suggests that
      these genes may be direct targets of the ATRA signaling pathway. A balanced
      functional network seemed to emerge, and it formed the foundation of decreased
      cellular proliferation, maintenance of cell viability, increased protein
      modulation, and promotion of granulocytic maturation. Several cytosolic signaling
      pathways, including JAKs/STAT and MAPK, may also be implicated in the symphony of
      differentiation. (Blood. 2000;96:1496-1504)

PMID- 10942399
TI  - Antileukemic efficacy of 2-deoxycoformycin in monocytic leukemia cells.
AB  - 2'-Deoxycoformycin (dCF) as a single agent has been reported to be less effective
      against myeloid than against lymphoid malignancies in clinical trials. However,
      previous studies have shown that in the presence of 2'-deoxyadenosine (dAd),
      human monocytoid leukemia cell lines are much more sensitive to dCF with regard
      to the inhibition of cell proliferation. Thus, dCF might be useful for treating
      monocytoid leukemia with the aid of dAd analogs. The antiproliferative effects of
      dCF in combination with dAd or its derivatives were examined on normal and
      malignant blood and bone marrow cells. In the presence of 10 micromol/L dAd, the
      concentration of dCF required to inhibit the viability of primary monocytoid
      leukemia cells was much lower than that required to inhibit normal or non
      monocytoid leukemic cells. Among the dAd analogs, 9-beta-D
      arabinofuranosyladenine (AraA) was also effective in combination with dCF.
      Athymic nude mice were inoculated with human monocytoid leukemia U937 cells and
      treated with dCF or a dAd analog or both. Although dCF alone slightly but
      significantly prolonged the survival of mice inoculated with U937 cells, combined
      treatment with dCF and AraA markedly prolonged their survival. These data suggest
      that the combination of dCF and AraA may be useful for the clinical treatment of
      acute monocytic leukemia. (Blood. 2000;96:1512-1516)

PMID- 10942400
TI  - High incidence of alternatively spliced forms of deoxycytidine kinase in patients
      with resistant acute myeloid leukemia.
AB  - Deficiency of functional deoxycytidine kinase (dCK) is a common characteristic
      for in vitro resistance to cytarabine (AraC). To investigate whether dCK is also
      a target for induction of AraC resistance in patients with acute myeloid leukemia
      (AML), we determined dCK messenger RNA (mRNA) expression in (purified) leukemic
      blasts and phytohemagglutinin-stimulated T cells (PHA T cells) from patients with
      chemotherapy-sensitive and chemotherapy-resistant AML. In control samples from
      healthy donors (PHA T cells and bone marrow), only wild-type dCK complementary
      DNA (cDNA) was amplified. Also, in (purified) leukemic blasts from patients with
      sensitive AML, only wild-type dCK cDNAs were observed. These cDNAs coded for
      active dCK proteins in vitro. However, in 7 of 12 (purified) leukemic blast
      samples from patients with resistant AML, additional polymerase chain reaction
      fragments with a deletion of exon 5, exons 3 to 4, exons 3 to 6, or exons 2 to 6
      were detected in coexpression with wild-type dCK. Deletion of exons 3 to 6 was
      also identified in 6 of 12 PHA T cells generated from the patients with resistant
      AML. The deleted dCK mRNAs were formed by alternative splicing and did code for
      inactive dCK proteins in vitro. These findings suggest that the presence of
      inactive, alternatively spliced dCK mRNA transcripts in resistant AML blasts may
      contribute to the process of AraC resistance in patients with AML. (Blood.
      2000;96:1517-1524)

PMID- 10942401
TI  - Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and
      may exert an antileukemic effect via inhibition of angiogenesis.
AB  - Arsenic trioxide (As(2)O(3)) has recently been used successfully in the treatment
      of acute promyelocytic leukemia and has been shown to induce partial
      differentiation and apoptosis of leukemic cells in vitro. However, the mechanism
      by which As(2)O(3) exerts its antileukemic effect remains uncertain. Emerging
      data suggest that the endothelium and angiogenesis play a seminal role in the
      proliferation of liquid tumors, such as leukemia. We have shown that activated
      endothelial cells release cytokines that may stimulate leukemic cell growth.
      Leukemic cells, in turn, can release endothelial growth factors, such as vascular
      endothelial growth factor (VEGF). On the basis of these observations, we
      hypothesized that As(2)O(3) may interrupt a reciprocal loop between leukemic
      cells and the endothelium by direct action on both cell types. We have shown that
      treatment of proliferating layers of human umbilical vein endothelial cells
      (HUVECs) with a variety of concentrations of As(2)O(3) results in a reproducible
      dose- and time-dependent sequence of events marked by change to an activated
      morphology, up-regulation of endothelial cell adhesion markers, and apoptosis.
      Also, treatment with As(2)O(3) caused inhibition of VEGF production in the
      leukemic cell line HEL. Finally, incubation of HUVECs with As(2)O(3) prevented
      capillary tubule and branch formation in an in vitro endothelial cell
      differentiation assay. In conclusion, we believe that As(2)O(3 )interrupts a
      reciprocal stimulatory loop between leukemic cells and endothelial cells by
      causing apoptosis of both cell types and by inhibiting leukemic cell VEGF
      production. (Blood. 2000;96:1525-1530)

PMID- 10942402
TI  - PML/RAR alpha fusion protein expression in normal human hematopoietic progenitors
      dictates myeloid commitment and the promyelocytic phenotype.
AB  - The role of fusion proteins in acute myeloid leukemia (AML) is well recognized,
      but the leukemic target cell and the cellular mechanisms generating the AML
      phenotype are essentially unknown. To address this issue, an in vitro model to
      study the biologic activity of leukemogenic proteins was established. Highly
      purified human hematopoietic progenitor cells/stem cells (HPC/HSC) in bulk cells
      or single cells are transduced with retroviral vectors carrying cDNA of the
      fusion protein and the green fluorescent protein (GFP), purified to homogeneity
      and induced into multilineage or unilineage differentiation by specific
      hematopoietic growth factor (HGF) combinations. Expression of PML/RAR alpha
      fusion protein in human HPC/HSC dictates the acute promyelocytic leukemia (APL)
      phenotype, largely through these previously unreported effects: rapid induction
      of HPC/HSC differentiation to the promyelocytic stage, followed by maturation
      arrest, which is abolished by retinoic acid; reprogramming of HPC commitment to
      preferential granulopoietic differentiation, irrespective of the HGF stimulus
      (transduction of single sibling HPC formally demonstrated this effect); HPC
      protection from apoptosis induced by HGF deprivation. A PML/RAR alpha mutated in
      the co-repressor N-CoR/histone deacetylase binding region lost these biologic
      effects, showing that PML/RAR alpha alters the early hematopoietic program
      through N-CoR-dependent target gene repression mechanisms. These observations
      identify the cellular mechanism underlying development of the APL phenotype,
      showing that the fusion protein directly dictates the specific lineage and
      differentiation stage of leukemic cells. (Blood. 2000;96:1531-1537)

PMID- 10942403
TI  - Peyer's patch eosinophils: identification, characterization, and regulation by
      mucosal allergen exposure, interleukin-5, and eotaxin.
AB  - The gastrointestinal immune system is traditionally thought to be composed of
      lymphocytes located within Peyer's patches and the lamina propria. We have
      recently reported that eosinophils also reside in the gastrointestinal tract
      during healthy states, in particular, within the lamina propria, and that these
      cells substantially increase after oral allergen exposure. We now demonstrate the
      presence of eosinophils in Peyer's patches and characterize the signals that
      regulate the accumulation of eosinophils in Peyer's patches. In contrast to the
      lamina propria, intestinal Peyer's patches have very low levels of eosinophils
      under healthy states. However, elevated levels of interleukin-5 (IL-5), generated
      by transgenic or pharmacologic approaches, result in a dramatic increase in
      eosinophil levels in Peyer's patches. Most eosinophils are located in the outer
      cortex and interfollicular regions of the Peyer's patches. To dissect the
      mechanism of eosinophil trafficking to Peyer's patches, the role of eotaxin was
      examined. Mice transgenic for IL-5 and genetically deficient in eotaxin were
      found to have reduced levels of eosinophils in Peyer's patches compared with IL-5
      transgenic mice. To prove that eosinophils also traffic to Peyer's patches in
      wild-type mice, allergic hypersensitivity was induced and Peyer's patches were
      examined. Exposure to mucosal allergen promoted marked accumulation of
      eosinophils in Peyer's patches and this process was attenuated in eotaxin
      deficient mice. In summary, these data demonstrate that elevated levels of IL-5
      and mucosal allergen exposure promote eotaxin-dependent eosinophil trafficking to
      Peyer's patches. These studies suggest that eosinophils may cooperate with
      lymphocytes in the development of mucosal immune responses in the
      gastrointestinal tract. (Blood. 2000;96:1538-1544)

PMID- 10942404
TI  - Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to
      erythropoietic protoporphyria.
AB  - Ferrochelatase (FECH; EC 4.99.1.1) catalyzes the terminal step of the heme
      biosynthetic pathway. Defects in the human FECH gene may lead to erythropoietic
      protoporphyria (EPP), a rare inherited disorder characterized by diminished FECH
      activity with protoporphyrin overproduction and subsequent skin photosensitivity
      and in rare cases liver failure. Inheritance of EPP appeared to be autosomal
      dominant with possible modulation by low expression of the wild-type FECH allele.
      Animal FECHs have been demonstrated to be [2Fe-2S] cluster-containing proteins.
      Although enzymatic activity and stability of the protein appear to be dependent
      on the presence of the [2Fe-2S] cluster, the physiologic role of the iron-sulfur
      center remains to be unequivocally established. Three of the 4 [2Fe-2S] cluster
      coordinating cysteines (ie, C403, C406, and C411 in the human enzyme) are located
      within the C-terminal domain. In this study 5 new mutations are identified in
      patients with EPP. Three of the point mutations, in 3 patients, resulted in FECH
      variants with 2 of the [2Fe-2S] cluster cysteines substituted with tyrosine,
      serine, and glycine (ie, C406Y, C406S, and C411G) and with undetectable enzymatic
      activity. Further, one of the patients exhibited a triple point mutation (T(1224)
      ->A, C(1225)-->T, and T(1231)-->G) leading to the N408K/P409S/C411G variant. This
      finding is entirely novel and has not been reported in EPP. The mutations of the
      codons for 2 of the [2Fe-2S] cluster ligands in patients with EPP supports the
      importance of the iron-sulfur center for the proper functioning of mammalian FECH
      and, in at least humans, its absence has a direct clinical impact. (Blood.
      2000;96:1545-1549)

PMID- 10942406
TI  - Epolones induce erythropoietin expression via hypoxia-inducible factor-1 alpha
      activation.
AB  - Induction of erythropoietin (Epo) expression under hypoxic conditions is mediated
      by the heterodimeric hypoxia-inducible factor (HIF)-1. Following binding to the
      3' hypoxia-response element (HRE) of the Epo gene, HIF-1 markedly enhances Epo
      transcription. To facilitate the search for HIF-1 (ant)agonists, a hypoxia
      reporter cell line (termed HRCHO5) was constructed containing a stably integrated
      luciferase gene under the control of triplicated heterologous HREs. Among various
      agents tested, we identified a class of substances called epolones, which induced
      HRE-dependent reporter gene activity in HRCHO5 cells. Epolones are fungal
      products known to induce Epo expression in hepatoma cells. We found that epolones
      (optimal concentration 4-8 micromol/L) potently induce HIF-1 alpha protein
      accumulation and nuclear translocation as well as HIF-1 DNA binding and reporter
      gene transactivation. Interestingly, the activity of a compound related to the
      fungal epolones, ciclopirox olamine (CPX), was blocked after addition of ferrous
      iron. This suggests that CPX might interfere with the putative heme oxygen
      sensor, as has been proposed for the iron chelator deferoxamine mesylate (DFX).
      However, about 10-fold higher concentrations of DFX (50-100 micromol/L) than CPX
      were required to maximally induce reporter gene activity in HRCHO5 cells.
      Moreover, structural, functional, and spectrophotometric data imply a
      chelator:iron stoichiometry of 1:1 for DFX but 3:1 for CPX. Because the iron
      concentration in the cell culture medium was determined to be 16 micromol/L, DFX
      but not CPX function can be explained by complete chelation of medium iron. These
      results suggest that the lipophilic epolones might induce HIF-1 alpha by
      intracellular iron chelation. (Blood. 2000;96:1558-1565)

PMID- 10942405
TI  - Sequential phosphorylation of protein band 3 by Syk and Lyn tyrosine kinases in
      intact human erythrocytes: identification of primary and secondary
      phosphorylation sites.
AB  - Treatment of intact human erythrocytes with pervanadate induces Tyr (Y)
      phosphorylation of the transmembrane protein band 3; in parallel, the activity of
      the immunoprecipitated tyrosine kinases Syk and Lyn is increased. When
      erythrocytes are incubated with pervanadate together with PP1, a specific
      inhibitor of Src kinases, including Lyn, the Y-phosphorylation of band 3 is only
      partially reduced. Indeed, the PP1-resistant phosphorylation of band 3 precedes
      and is a prerequisite for its coimmunoprecipitation with Lyn, which interacts
      with the phosphoprotein via the SH2 domain of the enzyme, as proven by binding
      competition experiments. Upon recruitment to primarily phosphorylated band 3, Lyn
      catalyzes the secondary phosphorylation of the transmembrane protein. These data
      are consistent with the view that band 3 is phosphorylated in intact erythrocytes
      by both PP1-resistant (most likely Syk) and PP1-inhibited (most likely Lyn)
      tyrosine kinases according to a sequential phosphorylation process. Similar
      radiolabeled peptide maps are obtained by tryptic digestion of (32)P-band 3
      isolated from either pervanadate-treated erythrocytes or red cell membranes
      incubated with exogenous Syk and Lyn. It has also been demonstrated by means of
      mass spectrometry that the primary phosphorylation of band 3 occurs at Y8 and
      Y21, while the secondary phosphorylation affects Y359 and Y904. (Blood.
      2000;96:1550-1557)

PMID- 10942407
TI  - Molecular heterogeneity of the Jk(null) phenotype: expression analysis of the
      Jk(S291P) mutation found in Finns.
AB  - Polymerase chain reaction genotyping of 32 unrelated Jk(null) individuals
      originating predominantly from Polynesia and Finland indicated that all were
      homozygous for the JK*B polymorphism and that 17 of 32, including the 14
      Polynesians, carried a 3'-acceptor splice site mutation of intron 5 that resulted
      in the skipping of exon 6 (called mutation Jk delta 6). The remaining 15 Jk(null)
      donors from Finland were homozygous for a new T871C transition resulting in a
      S291P amino acid substitution at a consensus N-glycosylation site of the Jk
      polypeptide. Transcription-translation assays revealed that the Jk(S291P) mutant
      was translated into a glycosylated component as efficiently as the wild-type Jk
      polypeptide (wt Jk)] in the presence of microsomes, thus indicating that the
      S291P mutation has no effect on the N-glycosylation pattern of the Jk protein.
      Expression studies in Xenopus oocytes revealed that the Jk(S291P) polypeptide
      functions as a urea transporter, but the transport activity and the membrane
      expression level of the mutant protein was reduced to a similar extent. A
      substantial fraction of the mutant protein was retained intracellularly
      suggesting that the transit to the plasma membrane was reduced, presumably
      because of the S-->P mutation. After transfection in erythroleukemia K562 cells
      the wild-type, but not the mutant, protein was efficiently expressed at the cell
      surface. Because the Jk(S291P) mutant polypeptide was not present in human red
      cells from Jk(null) individuals, expression data in the erythroid context clearly
      indicates that the S-->P mutation is the molecular basis of the Finnish Jk(null)
      phenotype. (Blood. 2000;96:1566-1573)

PMID- 10942408
TI  - Blood group A and B antigens are strongly expressed on platelets of some
      individuals.
AB  - It is widely thought that expression of ABH antigens on platelets is insufficient
      to materially affect the survival of ABH-incompatible platelets in transfusion
      recipients, but anecdotal reports of poor survival of A and B mismatched
      platelets suggest that this is not always the case. The A and B antigen
      expression on platelets of 100 group A(1) and group B blood donors was measured,
      and 7% and 4%, respectively, had platelets whose A and B antigen levels
      consistently exceeded the mean plus 2 SD. On the basis of flow cytometric and
      statistical analysis, donors whose platelets contained higher than normal levels
      of A antigen were subdivided into 2 groups, designated Type I and Type II ("high
      expressers"). Serum A(1)- and B-glycosyltransferase levels of A and B high
      expressers were significantly higher than those of group A(1) and B individuals
      with normal expression. H antigen levels were low on the red cells of high
      expressers, indicating that the anomaly affects other cell lineages.
      Immunochemical studies demonstrated high levels of A antigen on various
      glycoproteins (GPs) from high-expresser platelets, especially GPIIb and PECAM
      (CD31). The A(1) Type II high-expresser phenotype was inherited as an autosomal
      dominant trait in one family. The sequences of exons 5, 6, and 7 of the A(1)
      transferase gene of one Type II A(1) high expresser and exon 7 from 3 other genes
      were identical to the reported normal sequences. Further studies are needed to
      define the molecular basis for the high-expresser trait and to characterize its
      clinical implications. (Blood. 2000;96:1574-1581)

PMID- 10942409
TI  - Hydroxyurea-induced marked oscillations of platelet counts in patients with
      polycythemia vera.
AB  - Two prospectively studied patients with polycythemia vera (PV) whose platelet
      counts showed marked periodic fluctuation during treatment with hydroxyurea (HU)
      are reported. Cycle lengths in both were approximately 28 to 30 days. In one
      patient, the cyclic process was no longer evident when treatment with HU was
      withheld, and it reappeared on treatment rechallenge. Circulating thrombopoietin
      (TPO) levels fluctuated out of phase with the platelet count despite markedly
      reduced TPO-receptor (c-Mpl) expression in bone marrow megakaryocytes. These
      observations suggest that the cyclic phenomenon may be related to both a
      transient state of HU-induced depletion of megakaryocytes and a concentration
      dependent mitigation by TPO of the HU effect on megakaryocytes and their
      precursors. It is conceivable that the affected patients harbor a megakaryocyte
      progenitor pool whose apoptotic activity is differently modulated by either HU or
      high concentrations of TPO. (Blood. 2000;96:1582-1584)

PMID- 10942410
TI  - Somatic mosaicism and compound heterozygosity in female hemophilia B.
AB  - Sequencing the complete factor IX gene of 2 sisters with hemophilia B with
      different phenotypes and no family history of hemorrhagic diathesis revealed a
      common 5' splice site mutation in intron 3 (T6704C) in both and an additional
      missense mutation (I344T) in one. The presence of dysfunctional antigen in the
      latter strongly suggested that these mutations are in trans. Neither mutation was
      found in leukocyte DNA from the asymptomatic parents, but the mother was in
      somatic mosaicism for the shared splice site mutation. This case illustrates the
      importance of defining the phenotype and considering somatic mosaicism in
      sporadic cases. It underlines the limitations of complete gene sequencing for the
      detection of mosaicism and has implication for genetic counseling. (Blood.
      2000;96:1585-1587)

PMID- 10942411
TI  - Reassessment of interactions between hematopoietic receptors using common beta
      chain and interleukin-3-specific receptor beta-chain-null cells: no evidence of
      functional interactions with receptors for erythropoietin, granulocyte colony
      stimulating factor, or stem cell factor.
AB  - Mice lacking both the gene encoding the shared receptor for granulocyte
      macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5
      common beta-chain (B(c)) and the gene for the IL-3 specific receptor (BIL3) were
      generated. This was achieved by targeting the B(c) locus in embryonic stem cells
      that were heterozygous for a null mutation of BIL3. Cells from mice generated
      with the doubly targeted embryonic stem cells were unresponsive to all 3
      cytokines. Considerable previous data suggested a role for common beta-chain
      (beta(c)) in modulating signaling of cytokines including erythropoietin (EPO), G
      CSF, and stem cell factor (SCF). However, bone marrow cells from mice lacking
      beta(c) and beta(IL3) showed normal responsiveness to these cytokines. Thus,
      there was no evidence for a biologically significant interaction between
      signaling via beta(c) or beta(IL3) and signaling by EPO, G-CSF, or SCF.
      Previously documented biochemical phenomena, including receptor transmodulation,
      receptor transphosphorylation, and even direct physical interaction, involving
      the beta(c)/beta IL-3 receptor systems do not reflect genuine interactions of
      physiological significance in primary hematopoietic cells. This study provided
      results that challenge conclusions previously established using a variety of
      biochemical assays. (Blood. 2000;96:1588-1590)

PMID- 10942413
TI  - Coagulation and fibrinolytic activities in 2 siblings with beta(2)-glycoprotein I
      deficiency.
AB  - beta(2)-Glycoprotein I (beta(2)GPI) is a major antigen for antiphospholipid
      antibodies, and its multiple in vitro functions have been reported. This
      glycoprotein not only down-regulates thrombin formation by inhibiting contact
      activation or prothrombinase activity, but also up-regulates coagulation by
      reducing protein C anticoagulant activity. However, the in vivo roles of
      beta(2)GPI remain obscure. Coagulation and fibrinolytic characteristics were
      investigated in individuals with beta(2)GPI deficiency. An apparently healthy
      woman and her brother are homozygotes for beta(2)GPI deficiency. In these
      patients, Russell viper venom time was shortened (40.4 seconds; normal range,
      47.8 +/- 4.95 seconds), but all markers of thrombin generation and fibrin
      turnover were within normal ranges. Exogenous activated protein C adequately
      prolonged the clotting time of the beta(2)GPI-deficient plasma, and euglobulin
      lysis time was also normal. Thus, elevated thrombin generation, enhancement of
      activated protein C response, and an altered fibrinolytic system were not found
      in congenitally beta(2)GPI-deficient plasma. (Blood. 2000;96:1594-1595)

PMID- 10942412
TI  - Polarized expression of bone morphogenetic protein-4 in the human aorta-gonad
      mesonephros region.
AB  - In the mammal, definitive hematopoietic stem cells (HSCs) are first derived from
      mesodermal cells within a region of the embryonic para-aortic splanchnopleura
      known as the aorta-gonad-mesonephros (AGM). Within this region, HSCs are thought
      to arise from hemangioblast precursors located in the ventral wall of the dorsal
      aorta. However, the factors that regulate HSC development in vivo are still
      largely unknown. Bone morphogenetic protein (BMP)-4, a member of the transforming
      growth factor beta (TGF-beta) superfamily of growth factors, is a potent
      ventralizing factor and has been implicated in the commitment of embryonic
      mesodermal cells to a hematopoietic fate in a number of systems. In the human
      AGM, we find that BMP-4 is expressed at high levels, and with striking polarity,
      in a region of densely packed cells underlying intra-aortic hematopoietic
      clusters. In contrast, TGF-beta1 is expressed predominantly by hematopoietic
      cells within the clusters. These findings implicate both BMP-4 and TGF-beta1 in
      the initiation and regulation of hematopoiesis in the human AGM. Furthermore, the
      distribution of BMP-4 expression is highly suggestive of a direct role in the
      specification of human hematopoietic cells from embryonic mesoderm in vivo.
      (Blood. 2000;96:1591-1593)

PMID- 10942414
TI  - Human erythrocyte pyrimidine 5-nucleotidase, PN-I, is identical to p36, a protein
      associated to lupus inclusion formation in response to alpha-interferon.
AB  - Erythrocyte maturation is accompanied by RNA degradation and release of
      mononucleotides. We have previously purified PN-I, a pyrimidine nucleotidase
      whose deficiency is associated with hemolytic anemia. Computer-aided analysis of
      PN-I tryptic and CNBr peptide sequences revealed substantial identity with
      tryptic peptide sequences reported for p36, an alpha-interferon-induced protein.
      PN-I partial sequences were matched through the expressed sequence tag database
      with different human complementary DNA (cDNA) clones, whose sequences were
      exploited to screen a human placenta cDNA library. PN-I cDNA, coding for a 286
      residue protein, was expressed in Escherichia coli, yielding a fully active
      recombinant enzyme. The recombinant protein sequence comprised the peptide
      sequences determined for PN-I and p36. Rabbit antisera raised against two
      peptides deriving from p36 and PN-I tryptic digestions, respectively, recognized
      both wild-type and recombinant PN-I. Molecular properties of the two proteins
      were essentially the same. We conclude that p36 and PN-I are identical proteins.
      (Blood. 2000;96:1596-1598)

PMID- 10942415
TI  - Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions.
AB  - Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate
      the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus
      (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked
      immunosorbent assay was developed for vIL-6 and applied to the study of PEL.
      Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL),
      it was not detectable in any of the control effusions. As expected, all PEL
      effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained
      detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have
      previously been shown to induce vascular endothelial growth factor, which in turn
      can increase vascular permeability. The results of the current study suggest that
      these cytokines play a central role in the pathogenesis and manifestations of
      PEL. (Blood. 2000;96:1599-1601)

PMID- 10942416
TI  - Severe hereditary spherocytosis and distal renal tubular acidosis associated with
      the total absence of band 3.
AB  - Absence of band 3, associated with the mutation Coimbra (V488M) in the homozygous
      state, caused severe hereditary spherocytosis in a young child. Although prenatal
      testing was made available to the parents, it was declined. Because the fetus
      stopped moving near term, an emergency cesarean section was performed and a
      severely anemic, hydropic female baby was delivered. She was resuscitated and
      initially kept alive with respiratory assistance and hypertransfusion therapy.
      Cord blood smears revealed erythroblastosis, poikilocytosis, and red cells with
      stalk-like elongations. Band 3 and protein 4.2 were absent; spectrin, ankyrin,
      and glycophorin A were significantly reduced. Renal tubular acidosis was detected
      by the age of 3 months. Nephrocalcinosis appeared soon thereafter. After 3 years
      of follow-up the child is doing reasonably well on a regimen that includes
      regular blood transfusions and daily bicarbonate supplements. The long-term
      prognosis remains uncertain given the potential for hematologic and renal
      complications. (Blood. 2000;96:1602-1604)

PMID- 10942417
TI  - Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic
      large-cell lymphoma.
AB  - Oncogenic anaplastic lymphoma kinase (ALK) fusion proteins (nucleophosmin-ALK
      [NPM-ALK] and other variants) are expressed in many cases of anaplastic large
      cell lymphoma (ALCL) but are absent from normal tissues. The possibility that ALK
      proteins are immunogenic was investigated with the use of an immunocytochemical
      technique to screen plasma from ALK-positive ALCL on transfectants expressing ALK
      proteins and by an in vitro kinase assay. Circulating antibodies against NPM-ALK
      protein were present in all ALK-positive ALCL patients (11 out of 11 cases)
      studied while 10 patients also had antibodies recognizing normal ALK protein.
      Weak antibodies reactive with NPM-ALK (which may represent anti-NPM
      autoantibodies) were detected by the in vitro kinase assay in 3 of the 10 control
      samples (but not by immunocytochemistry). The presence of anti-ALK antibodies may
      be relevant to the relatively good prognosis of ALK-positive ALCL. The
      immunocytochemical technique for detecting anti-ALK activity is simple and
      semiquantative and may provide a means of detecting B-cell responses to other
      tumor-associated molecules. (Blood. 2000;96:1605-1607)

PMID- 10942418
TI  - Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg
      syndrome.
AB  - Waardenburg syndrome (WS) is an autosomal dominant disorder with an incidence of
      1 in 40 000 that manifests with sensorineural deafness and pigmentation defects.
      It is classified into four types depending on the presence or absence of
      additional symptoms. WS1 and WS3 are due to mutations in the PAX3 gene whereas
      some WS2 cases are associated with mutations in the microphthalmia-associated
      transcription factor (MITF) gene. The WS4 phenotype can result from mutations in
      the endothelin-B receptor gene (EDNRB), in the gene for its ligand, endothelin-3
      (EDN3), or in the SOX10 gene. PAX3 has been shown to regulate MITF gene
      expression. The recent implication of SOX10 in WS4 prompted us to test whether
      this transcription factor, known to cooperate in vitro with PAX3, is also able to
      regulate expression from the MITF promoter. Here we show that SOX10, in synergy
      with PAX3, strongly activates MITF expression in transfection assays. Analyses
      revealed that PAX3 and SOX10 interact directly by binding to a proximal region of
      the MITF promoter containing binding sites for both factors. Moreover, SOX10 or
      PAX3 mutant proteins fail to transactivate this promoter, providing further
      evidence that the two genes act in concert to directly regulate expression of
      MITF. In situ hybridization experiments carried out in the dominant megacolon
      (DOM:) mouse, confirmed that SOX10 dysfunction impairs MITF: expression as well
      as melanocytic development and survival. These experiments, which demonstrate an
      interaction between three of the genes that are altered in WS, could explain the
      auditory-pigmentary symptoms of this disease.

PMID- 10942419
TI  - Mutations in the N-terminus of the X-linked retinitis pigmentosa protein RP2
      interfere with the normal targeting of the protein to the plasma membrane.
AB  - The X-linked retinitis pigmentosa (XLRP) gene, RP2, codes for a novel 350 amino
      acid protein of unknown function. We have identified putative sites for N
      terminal acyl modification by myristoylation and palmitoylation in the RP2
      protein. The RP2 protein is expressed ubiquitously in human tissues at relatively
      low levels (0.01% of total protein) and has a predominantly plasma membrane
      localization in cultured cells, as would be expected if the protein was subject
      to dual N-terminal acylation. Furthermore, mutagenesis of residues potentially
      required for N-terminal acylation prevents targeting of RP2 to the plasma
      membrane and the N-terminal 15 amino acids of the protein appear to be sufficient
      for this targeting. Our data suggest that the protein is dually acylated and that
      the palmitoyl moiety is responsible for targeting of the myristoylated protein
      from intracellular membranes to the plasma membrane. The effect of two mutations,
      which have been reported as causes of XLRP, R118H and DeltaS6, were investigated.
      The R118H mutation does not affect the normal plasma membrane localization of
      RP2; in contrast, the DeltaS6 mutation interferes with the targeting of the
      protein to the plasma membrane. Therefore, the DeltaS6 mutation may cause XLRP
      because it prevents normal amounts of RP2 reaching the correct cellular locale,
      whereas the R118H mutation is in a region of the protein that is vital for
      another aspect of RP2 function in the retina.

PMID- 10942420
TI  - Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.
AB  - We have previously developed a functional assay in yeast for the copper
      transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant
      ATP7B proteins revealed that several were able to completely, or nearly
      completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was
      disrupted, indicating that these ATP7B proteins retained copper transport
      activity. We analyzed the intracellular localization of these active WND ATP7B
      variant proteins using transient transfection of Chinese hamster ovary cells and
      triple-label immunofluorescence microscopy, as a second possible aspect of
      defective function. Two ATP7B variants, Asp765Asn and Leu776Val, which have
      normal copper transport activity in yeast, retained partial normal Golgi network
      localization, but were predominantly mislocalized throughout the cell. Asp765Asn
      and Leu776Val proteins were capable of only partial copper-dependent
      redistribution. WND variant protein Arg778Leu, which has defective function in
      yeast, was extensively mislocalized, presumably to the endoplasmic reticulum.
      ATP7B variant proteins Gly943Ser, which has nearly normal function in yeast, and
      CysProCys/Ser (mutation of the conserved CysProCys motif to SerProSer), inactive
      in yeast, were localized normally but were unable to redistribute in response to
      copper. Localization data from this study, combined with functional data from our
      yeast studies, provide a biochemical mechanism that can explain in part the
      variable biochemical features of WND, in particular the normal holo-ceruloplasmin
      levels observed in some patients. Our data have direct implications for WND
      diagnosis, indicating that decreased serum ceruloplasmin concentration is not
      likely to be observed with certain genetic variants of WND.

PMID- 10942421
TI  - The X-linked mouse mutation Bent tail is associated with a deletion of the Zic3
      locus.
AB  - Bent tail (BN:) is a spontaneous, semi-dominant mutation on the mouse X
      chromosome that produces tail deformities and, rarely, open neural tube defects.
      Analysis of 292 normal male and affected male and female progeny from an
      intraspecific back-cross involving BN: supports a gene order of cen-DXMit89-18.5
      +/- 2.3 cM-DXMit166-1.4 +/- 0.7 cM-BN:-1.0 +/- 0.6 cM-DXMit140 -4.8 +/- 1.3 cM
      DXBay6-tel. A high frequency of sex chromosomal non-disjunction, unrelated to the
      BN: mutation, was also identified in the background strain. Refined genetic and
      physical mapping of the BN: critical region demonstrate that the mutation is
      associated with a <170 kb submicroscopic deletion that includes the anonymous
      microsatellite marker DXMit208 as well as the entire Zic3 locus. Human mutations
      in ZIC3 are associated with left-right axis malformations (MIM 306955, 208530,
      207100). Abnormalities of abdominal and thoracic situs were also detected in
      viable BN: males and females. The presence of anal and spinal abnormalities in
      some of the human patients and the deletion of Zic3 in BN: mice support a key
      role for this gene in neural tube development and closure.

PMID- 10942422
TI  - Linkage and association of tumor necrosis factor receptor 2 locus with
      hypertension, hypercholesterolemia and plasma shed receptor.
AB  - Tumor necrosis factor (TNF) receptor 2 (TNF-R2) has been implicated in insulin
      resistance and metabolic syndrome disorders, one of which is hypertension (HT).
      We therefore decided to test markers in and near the TNF-R2 gene (TNFRSF1B) for
      linkage and association with HT, as well as hypercholesterolemia, and plasma
      levels of the shed soluble receptor (sTNF-R2). The linkage study, which involved
      200 HT Anglo-Celtic Caucasian sibpairs, indicated a sharp, significant linkage
      peak centered at TNFRSF1B (multipoint maximum LOD score = 2. 6 and 3.1 by
      weighted and unweighted MAPMAKER/SIBS, respectively; two-point LOD scores = 2.9
      and 3.9 by weighted and unweighted SPLINK, respectively; P = 10(-4) by identical
      by-state chi(2)). The case-control study in 134 unrelated HTs who were the
      offspring of two HT parents and 197 normotensives (NTs) whose parents were both
      NTs, indicated possible association of TNFRSF1B with HT by haplotype analysis (P
      = 0.008). Plasma sTNF-R2 was elevated in HTs (P < 0. 0001) and showed a
      correlation with systolic and diastolic blood pressure (BP) (P < 0.0002). A
      genotypic effect of TNFRSF1B on plasma sTNF-R2, as well as total, low and high
      density lipoprotein cholesterol, and diastolic BP was observed. These
      observations are consistent with a scheme leading to raised BP and
      hypercholesterolemia. In conclusion, TNFRSF1B may be a candidate gene for HT and
      other metabolic syndrome abnormalities.

PMID- 10942423
TI  - The Conradi-Hunermann-Happle syndrome (CDPX2) and emopamil binding protein: novel
      mutations, and somatic and gonadal mosaicism.
AB  - The Conradi-Hunermann-Happle (CHH) syndrome (X-chromosomal dominant
      chondrodysplasia punctata type II; MIM 302960) is an X-linked dominant disorder
      that is characterized by ichthyosis, chondrodysplasia punctata, cataracts and
      short stature. The disease occurs almost exclusively in females and shows
      increased disease expression in successive generations (anticipation). Recently,
      causative mutations in the emopamil binding protein (EBP) have been identified.
      To better appreciate the genetics of this syndrome we analyzed the EBP gene in
      seven independent families using PCR, conformation-sensitive gel electrophoresis,
      direct sequencing and restriction enzyme analysis. We found five novel mutations:
      three nonsense mutations in exon 2 and exon 3 and two frameshift mutations, one
      deletion in exon 4 and an insertion in exon 5. In two families, known mutations
      affecting exon 2 were identified. Surprisingly, we failed to detect the mutation
      in a grandmother exhibiting minor disease symptoms such as sectorial cataract and
      attribute this to gonadal and somatic mosaicism. Gonadal mosaicism appeared also
      to be involved in the case of healthy parents having two affected girls, one of
      whom died due to the disease. We conclude that gonadal mosaicism has to be
      considered when dealing with seemingly sporadic cases.

PMID- 10942424
TI  - CAG tract of MJD-1 may be prone to frameshifts causing polyalanine accumulation.
AB  - Machado-Joseph disease (MJD) is one of several disorders caused by the expansion
      of a coding CAG repeat (exp-CAG). The presence of intranuclear inclusions (INIs)
      in patients and cellular models of exp-CAG-associated diseases has lead to a
      nuclear toxicity model. Similar INIs are found in oculopharyngeal muscular
      dystrophy, which is caused by a short expansion of an alanine-encoding GCG
      repeat. Here we propose that transcriptional or translational frameshifts
      occurring within expanded CAG tracts result in the production and accumulation of
      polyalanine-containing mutant proteins. We hypothesize that these alanine
      polymers deposit in cells forming INIs and may contribute to nuclear toxicity. We
      show evidence that supports our hypothesis in lymphoblast cells from MJD
      patients, as well as in pontine neurons of MJD brain and in in vitro cell culture
      models of the disease. We also provide evidence that alanine polymers alone are
      harmful to cells and predict that a similar pathogenic mechanism may occur in the
      other CAG repeat disorders.

PMID- 10942425
TI  - Creation of a mouse model for non-neurological (type B) Niemann-Pick disease by
      stable, low level expression of lysosomal sphingomyelinase in the absence of
      secretory sphingomyelinase: relationship between brain intra-lysosomal enzyme
      activity and central nervous system function.
AB  - Most lysosomal storage diseases result in neurodegeneration, but deficiencies in
      the same enzymes can also lead to syndromes without neurologic manifestations.
      The hypothesis that low levels of residual, intra-lysosomal enzymatic activities
      in the central nervous system (CNS) are protective has been difficult to prove
      because of inconsistencies in assays of tissue samples. Experimental correction
      of lysosomal enzyme deficiencies in animal models suggests that low-level
      enzymatic activity may reduce CNS pathology, but these results are difficult to
      interpret owing to the partial and transient nature of the improvements, the
      presence of secretory hydrolases, and other confounding factors. Using a novel
      transgenic/knockout strategy to manipulate the intracellular targeting of a
      hydrolase, we created a mouse that stably expresses low levels of lysosomal
      sphingomyelinase (L-SMase) in the complete absence of secretory sphingomyelinase
      (S-SMase). The brains of these mice exhibited 11.5-18.2% of wild-type L-SMase
      activity, but the cerebellar Purkinje cell layer, which is lost by 4 months of
      age in mice completely lacking L- and S-SMase, was preserved for at least 8
      months. The L-SMase activities in other organs were 1-14% of wild-type levels,
      and by 8 months of age all peripheral organs had accumulated sphingomyelin and
      demonstrated pathological intracellular inclusions. Most importantly, L-SMase
      expressing mice showed no signs of the severe neurologic disease observed in
      completely deficient mice, and their life span and general health were
      essentially normal. These findings show that stable, continuous, low-level
      expression of intra-lysosomal enzyme activity in the brain can preserve CNS
      function in the absence of secretory enzyme or other confounding factors.

PMID- 10942426
TI  - Characterization of a nuclear 20S complex containing the survival of motor
      neurons (SMN) protein and a specific subset of spliceosomal Sm proteins.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease of motor neurons
      caused by reduced levels of functional survival of motor neurons (SMN) protein.
      Cytoplasmic SMN directly interacts with spliceosomal Sm proteins and facilitates
      their assembly onto U snRNAs. Nuclear SMN, in contrast, mediates recycling of pre
      mRNA splicing factors. In this study, we have addressed the function of SMN in
      the nucleus. We show that a monoclonal antibody directed against SMN inhibits pre
      mRNA splicing. Interestingly, the mode of inhibition suggests a novel role for
      SMN in splicing that occurs prior to, or in addition to, its role in recycling.
      Using biochemical fractionation and anti-SMN immunoaffinity chromatography, we
      identified two distinct nuclear SMN complexes termed NSC1 and NSC2. The
      biochemical properties and protein composition of NSC1 were determined in detail.
      NSC1 migrates in sucrose gradients as a U snRNA-free 20S complex containing at
      least 10 proteins. In addition to SMN, these include the SMN-interacting protein
      1 (SIP-1), the putative helicase dp103/Gemin3, the novel dp103/Gemin3-interacting
      protein GIP1/Gemin4 and three additional proteins with apparent masses of 43, 33
      and 18 kDa, respectively. Most surprisingly, NSC1 also contains a specific subset
      of spliceosomal Sm proteins. This shows that the SMN-Sm protein interaction is
      not restricted to the cytoplasm. Our data imply that nuclear SMN affects splicing
      by modulating the Sm protein composition of U snRNPs.

PMID- 10942427
TI  - Molecular effects of calcium binding mutations in Marfan syndrome depend on
      domain context.
AB  - Mutations in the human fibrillin-1 (FBN-1) gene cause Marfan syndrome (MFS), an
      autosomal dominant disease of connective tissue. Fibrillin-1, a 350 kDa
      extracellular calcium binding protein, is a major structural component of 10-12
      nm microfibrils and consists predominantly of two repeated module types: the
      calcium binding epidermal growth factor-like (cbEGF) domain and the transforming
      growth factor beta1 binding protein-like (TB) domain. A group of reported FBN-1
      mutations is predicted to reduce calcium binding to cbEGF domains by removal of a
      side chain ligand for calcium. These mutations occur in two protein domain
      contexts, either in a cbEGF preceded by a TB domain or in a cbEGF preceded by
      another cbEGF domain. In this study we have used three proteases to probe
      structural changes caused by an N2144S MFS calcium binding mutation in a TB6
      cbEGF32 and a cbEGF32-33 domain pair, and an N2183S mutation in the cbEGF32-33
      pair. N-terminal sequence analysis of domain pairs digested in the presence and
      absence of calcium show that: (i) domain interactions between TB6 and cbEGF32 are
      calcium independent, despite the presence of a calcium binding site in cbEGF32;
      (ii) domain interactions between cbEGF32 and cbEGF33 are calcium dependent; and
      (iii) an N-->S mutation causes increased proteolytic susceptibility only when
      located in cbEGF33, consistent with a key role for interdomain calcium binding in
      rigidifying cbEGF domain linkages. These data demonstrate for the first time that
      the structural consequences of calcium binding mutations in fibrillin-1 cbEGF
      domains can be influenced by domain context.

PMID- 10942428
TI  - Identification of PEX3 as the gene mutated in a Zellweger syndrome patient
      lacking peroxisomal remnant structures.
AB  - Peroxisome biogenesis disorders, of which 13 complementation groups have been
      identified, are subdivided with regard to two major dysfunctions: peroxisomal
      matrix protein import and peroxisomal membrane synthesis. Detectable remnant
      membrane structures are evident only in the former. Molecular defects have been
      defined in 10 PEX genes, including eight related to protein import and two to
      membrane synthesis. We now have evidence that the human complete cDNA encoding
      Pex3p, a peroxisomal membrane protein (PMP) factor for the proper localization of
      PMPs, rescues the import of both PMP and the matrix protein in fibroblasts from a
      Zellweger syndrome patient of complementation group G. This patient was
      homozygous for a 1 base insertion in the codon for V182, which resulted in a
      change of codon (182-183) and introduced a termination codon (184), which
      inactivated PMP and matrix protein import by Pex3p. A PEX3-defective CHO mutant
      clone, ZPG208, was of the same complementation group as group G.

PMID- 10942429
TI  - A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and
      premature fusion of calvarial sutures.
AB  - Pfeiffer syndrome is a classic form of craniosynostosis that is caused by a
      proline-->arginine substitution at amino acid 252 (Pro252Arg) in fibroblast
      growth factor receptor 1 (FGFR1). Here we show that mice carrying a Pro250Arg
      mutation in Fgfr1, which is orthologous to the Pfeiffer syndrome mutation in
      humans, exhibit anterio-posteriorly shortened, laterally widened and vertically
      heightened neurocraniums. Analysis of the posterior and anterior frontal,
      sagittal and coronal sutures of early post-natal mutant mice revealed premature
      fusion. The sutures of mutant mice had accelerated osteoblast proliferation and
      increased expression of genes related to osteoblast differentiation, suggesting
      that bone formation at the sutures is locally increased in Pfeiffer syndrome. Of
      note, dramatically increased expression of core-binding transcription factor
      alpha subunit type 1 (Cbfa1) accompanied premature fusion, suggesting that Cbfa1
      may be a downstream target of Fgf/Fgfr1 signals. This was confirmed in vitro,
      where we demonstrate that transfection with wild-type or mutant Fgfr1 induces
      Cbfa1 expression. The induced expression was also observed using Fgf ligands
      (Fgf2 and Fgf8). These studies provide direct genetic evidence that the Pro252Arg
      mutation in FGFR1 causes human Pfeiffer syndrome and uncovers a molecular
      mechanism in which Fgf/Fgfr1 signals regulate intramembraneous bone formation by
      modulating Cbfa1 expression.

PMID- 10942430
TI  - Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones
      with truncated N-terminal huntingtin: their role in suppression of aggregation
      and cellular toxicity.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by polyglutamine expansion in the disease protein, huntingtin. In HD
      patients and transgenic mice, the affected neurons form characteristic ubiquitin
      positive nuclear inclusions (NIs). We have established ecdysone-inducible stable
      mouse Neuro2a cell lines that express truncated N-terminal huntingtin (tNhtt)
      with different polyglutamine lengths which form both cytoplasmic and nuclear
      aggregates in a polyglutamine length- and inducer dose-dependent manner. Here we
      demonstrate that newly synthesized polyglutamine-expanded truncated huntingtin
      interacts with members of Hsp40 and Hsp70 families of chaperones in a
      polyglutamine length-dependent manner. Of these interacting chaperones, only Hdj
      2 and Hsc70 frequently (Hdj-2 > Hsc70) co-localize with both the aggregates in
      the cellular model and with the NIs in the brains of HD exon 1 transgenic mice.
      However, Hdj-2 and Hsc70 do not co-localize with cytoplasmic aggregates in the
      brains of transgenic mice despite these chaperones being primarily localized in
      the cytoplasmic compartment. This strongly suggests that the chaperone
      interaction and their redistribution to the aggregates are two completely
      different phenomena of the cellular unfolded protein response. This unfolded
      protein response is also evident from the dramatic induction of Hsp70 on
      expression of polyglutamine-expanded protein in the cellular model. Transient
      overexpression of either Hdj-1 or Hsc70 suppresses the aggregate formation;
      however, suppression efficiency is much higher in Hdj-1 compared with Hsc70.
      Overexpression of Hdj-1 and Hsc70 is also able to protect cell death caused by
      polyglutamine-expanded tNhtt and their combination proved to be most effective.

PMID- 10942431
TI  - Molecular and genetic characterization of sarcospan: insights into sarcoglycan
      sarcospan interactions.
AB  - Autosomal recessive limb girdle muscular dystrophies 2C-2F represent a family of
      diseases caused by primary mutations in the sarcoglycan genes. We show that
      sarcospan, a novel tetraspan-like protein, is also lost in patients with either a
      complete or partial loss of the sarcoglycans. In particular, sarcospan was absent
      in a gamma-sarcoglycanopathy patient with normal levels of alpha-, beta- and
      delta-sarcoglycan. Thus, it is likely that assembly of the complete, tetrameric
      sarcoglycan complex is a prerequisite for membrane targeting and localization of
      sarcospan. Based on our findings that sarcospan is integrally associated with the
      sarcoglycans, we screened >50 autosomal recessive muscular dystrophy cases for
      mutations in sarcospan. Although we identified three intragenic polymorphisms, we
      did not find any cases of muscular dystrophy associated with primary mutations in
      the sarcospan gene. Finally, we have identified an important case of limb girdle
      muscular dystrophy and cardiomyopathy with normal expression of sarcospan. This
      patient has a primary mutation in the gamma-sarcoglycan gene, which causes
      premature truncation of gamma-sarcoglycan without affecting assembly of the
      mutant gamma-sarcoglycan into a complex with alpha-, beta- and delta-sarcoglycan
      and sarcospan. This is the first demonstration that membrane expression of a
      mutant sarcoglycan-sarcospan complex is insufficient in preventing muscular
      dystrophy and cardiomyopathy and that the C-terminus of gamma-sarcoglycan is
      critical for the functioning of the entire sarcoglycan-sarcospan complex. These
      findings are important as they contribute to a greater understanding of the
      structural determinants required for proper sarcoglycan-sarcospan expression and
      function.

PMID- 10942432
TI  - Genomic sequence and transcriptional profile of the boundary between
      pericentromeric satellites and genes on human chromosome arm 10q.
AB  - The organization of centromeric heterochromatin has been established in a number
      of eucaryotes but remains poorly defined in human. Here we present 1025 kb of
      contiguous human genomic sequence which links pericentromeric satellites to the
      RET proto-oncogene in 10q11.2 and is presumed to span the transition from centric
      heterochromatin to euchromatin on this chromosome arm. Two distinct domains can
      be defined within the sequence. The proximal approximately 240 kb consists of
      arrays of satellites and other tandem repeats separated by tracts of complex
      sequence which have evolved by pericentromeric-directed duplication. Analysis of
      32 human paralogues of these sequences indicates that most terminate at or within
      repeat arrays, implicating these repeats in the interchromosomal duplication
      process. Corroborative PCR-based analyses establish a genome-wide correlation
      between the distribution of these paralogues and the distribution of satellite
      families present in 10q11. In contrast, the distal approximately 780 kb contains
      few tandem repeats and is largely chromosome specific. However, a minimum of
      three independent intrachromosomal duplication events have resulted in >370 kb of
      this sequence sharing >90% identity with sequences on 10p. Using computer-based
      analyses and RT-PCR we confirm the presence of three genes within the sequence,
      ZNF11/33B, KIAA0187 and RET, in addition to five transcripts of unknown
      structure. All of these transcribed sequences map distal to the satellite arrays.
      The boundary between satellite-rich interchromosomally duplicated DNA and
      chromosome-specific DNA therefore appears to define a transition from
      pericentromeric heterochromatin to euchromatin on the long arm of this
      chromosome.

PMID- 10942433
TI  - Evidence of a linkage disequilibrium between polymorphisms in the human estrogen
      receptor alpha gene and their relationship to bone mass variation in
      postmenopausal Italian women.
AB  - Bone mineral density (BMD), the major determinant of osteoporotic fracture risk,
      has a strong genetic component. The discovery that inactivation of estrogen
      receptor alpha (ERalpha) gene is associated with low BMD indicated ERalpha as a
      candidate gene for osteoporosis. We have investigated the role of three ERalpha
      gene polymorphisms [intron 1 PVU:II and XBA:I RFLPs and TA dinucleotide repeat
      polymorphism 5' upstream of exon 1] in 610 postmenopausal women. There was a
      strong linkage disequilibrium between intron 1 polymorphic sites and also between
      these sites and the microsatellite (TA)(n) dinucleotide polymorphism, with a high
      degree of coincidence of the short TA alleles and the presence of PVU:II and
      XBA:I restriction sites. No significant relationship between intron 1 RFLPs and
      BMD was observed. A statistically significant correlation between (TA)(n) repeat
      allelic variants and lumbar BMD was observed (P = 0.04, ANCOVA), with subjects
      with a low number of repeats (TA < 15) showing the lowest BMD values. We observed
      a statistically significant difference in the mean +/- SD number of TA repeats
      between analyzed women with a vertebral fracture (n = 73) and the non-fracture
      group, equivalent to 2.9 (95% CI 1.56-5.72) increased fracture risk in women with
      a low number of repeats (TA < 15). We conclude that in this large population
      sample the (TA)(n) dinucleotide repeat polymorphism at the 5' end of the ERalpha
      gene accounts for part of the heritable component of BMD and might prove useful
      in the prediction of vertebral fracture risk in postmenopausal osteoporosis.

PMID- 10942434
TI  - Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor
      growth, plays a critical role in the maintenance of retinal structure and in
      neural tube closure (Knobloch syndrome).
AB  - Knobloch syndrome (KS) is an autosomal recessive disorder defined by the
      occurrence of high myopia, vitreoretinal degeneration with retinal detachment,
      macular abnormalities and occipital encephalocele. The KS causative gene had been
      assigned to a 4.3 cM interval at 21q22.3 by linkage analysis of a large
      consanguineous Brazilian family. We reconstructed the haplotypes of this family
      with ten additional markers (five were novel) and narrowed the candidate interval
      to a region of <245 kb, which contains 24 expressed sequence tags, the KIAA0958
      gene and the 5' end of the COL18A1 gene. We identified a homozygous mutation at
      the AG consensus acceptor splice site of COL18A1 intron 1 exclusively among the
      12 KS patients, which was not found among 140 control chromosomes. This mutation
      predicts the creation of a stop codon in exon 4 and therefore the truncation of
      the alpha1(XVIII) collagen short form, which was expressed in human adult retina.
      These findings provide evidence that KS is caused by mutations in COL18A1 which,
      therefore, has a major role in determining the retinal structure as well as in
      the closure of the neural tube. Therefore, we show for the first time that the
      absence of a collagen isoform impairs embryonic cell proliferation and/or
      migration as a primary or secondary effect.

PMID- 10942435
TI  - Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant
      osteopetrosis.
AB  - Although the gene defects for several mouse mutants with severe osteopetrosis are
      known, the genes underlying human infantile malignant recessive osteopetrosis
      remain elusive. Osteopetrosis is thought to be caused by a defect in osteoclast
      function. These cells degrade bone material in a tightly sealed extracellular
      compartment that is acidified by a vacuolar (V)-type H(+)-ATPase. Genes encoding
      components of the acidification machinery are candidate genes for osteopetrosis.
      In five of ten patients with infantile malignant osteopetrosis, we now
      demonstrate five different mutations in OC116, the gene encoding the a3 subunit
      of the V-ATPase from osteoclasts. Two independent patients were homozygous for
      mutations that predict a total loss of function by severely truncating the
      protein. By affecting a splice site, another homozygous mutation deletes 14 amino
      acids within the N-terminus, which interacts with other subunits of the proton
      pump. On the other hand, in four patients no mutations were found, and one
      patient from a consanguineous family did not show homozygosity at the OC116
      locus, suggesting that mutations in at least one different gene may underlie
      osteopetrosis. Our work shows that mutations in the gene encoding the a3 subunit
      of the proton pump are a rather common cause of infantile osteopetrosis and
      suggests that this disease is genetically heterogeneous.

PMID- 10942436
TI  - The genome project alibi: towards a genetic reductionism?

PMID- 10942437
TI  - Writing for journals: a paradigm lost?

PMID- 10942438
TI  - Wealth and health in relation to birth defects mortality.

PMID- 10942439
TI  - Medical genetics, the human genome project and public health.

PMID- 10942440
TI  - Coffee, pancreatic cancer and the question of causation.

PMID- 10942441
TI  - Exposures, mutations and the history of causality.

PMID- 10942442
TI  - Coffee, K-ras mutations and pancreatic cancer: a heterogeneous aetiology or an
      artefact?

PMID- 10942443
TI  - Coffee, pancreatic cancer, and K-ras mutations: updating the research agenda.

PMID- 10942444
TI  - Infant mortality and congenital anomalies from 1950 to 1994: an international
      perspective.
AB  - STUDY OBJECTIVE: To provide an international perspective on the impact of
      congenital anomalies on infant mortality from 1950 to 1994. DESIGN: Population
      based study based on data obtained from vital statistics reported to the World
      Health Organisation. SETTINGS: 36 countries from Europe, the Middle East, the
      Americas, Asia, and the South Pacific. RESULTS: On average, infant mortality
      declined 68.8 per cent from 1950 to 1994. In the countries studied, infant
      mortality attributable to congenital anomalies decreased by 33.4 per cent,
      although it recently increased in some countries in Central and Latin America and
      in Eastern Europe. Anomalies of the heart and of the central nervous system
      accounted for 48.9 per cent of infant deaths attributable to congenital
      anomalies. During 1990-1994, infant mortality attributable to congenital
      anomalies was inversely correlated to the per capita gross domestic product in
      the countries studied. At the same time, the proportion of infant deaths
      attributable to congenital malformations was directly correlated with the per
      capita gross domestic product. CONCLUSIONS: Congenital malformations account for
      an increasing proportion of infant deaths in both developed and developing
      countries. Infant mortality attributable to congenital anomalies is higher in
      poorer countries although as a proportion of infant deaths it is greater in
      wealthier countries. Conditions such as spina bifida, whose occurrence can be
      reduced through preventive strategies, still cause many infant deaths. The
      apparent increase of infant mortality because of congenital anomalies in some
      countries should be investigated to confirm the finding, find the causes, and
      provide prevention opportunities.

PMID- 10942445
TI  - Determinants of leisure time physical activity in rural compared with urban older
      and ethnically diverse women in the United States.
AB  - STUDY OBJECTIVE: Determinants of leisure time physical activity (LTPA) in rural
      middle aged and older women of diverse racial and ethnic groups are not well
      understood. This study examined: (1) urban-rural differences in LTPA by
      sociodemographic factors, (2) urban-rural differences in LTPA determinants, and
      (3) the pattern of relations between LTPA determinants and LTPA. DESIGN: A
      modified version of the sampling plan of the Behavioral Risk Factor Surveillance
      Survey (BRFSS) was used. Zip codes were selected with 20% or more of each of the
      following race/ethnic groups: African American, American Indian/Alaskan Native
      (AI/AN), and Hispanic. A comparison group of white women were also surveyed using
      standard BRFSS techniques. PARTICIPANTS: Rural (n=1242) and urban (n=1096) women
      aged 40 years and older from the US Women's Determinants Study. MAIN RESULTS:
      Rural women, especially Southern and less educated women, were more sedentary
      than urban women. Rural women reported more personal barriers to LTPA, cited
      caregiving duties as their top barrier (compared with lack of time for urban
      women), and had greater body mass indices. Rural women were less likely to report
      sidewalks, streetlights, high crime, access to facilities, and frequently seeing
      others exercise in their neighbourhood. Multivariate correlates of sedentary
      behaviour in rural women were AI/AN and African American race, older age, less
      education, lack of enjoyable scenery, not frequently seeing others exercise,
      greater barriers, and less social support (p<0.05); and in urban women, older
      age, greater barriers, less social support (p<0.05), and less education (p<0.09).
      CONCLUSIONS: Rural and urban women seem to face different barriers and enablers
      to LTPA, and have a different pattern of determinants, thus providing useful
      information for designing more targeted interventions.

PMID- 10942446
TI  - Passive smoking at work: the short-term cost.
AB  - STUDY OBJECTIVE: To estimate the impact of passive smoking at work on use of
      health care services and absenteeism. DESIGN: Cross sectional survey. SETTING: A
      workforce in Hong Kong. PARTICIPANTS: 5142 never-smoking police officers in a
      total sample of 9926. MAIN RESULTS: A consistently strong association was found
      among men between length of time exposed to passive smoking at work and self
      reported consultations with a doctor, use of medicines and time off work. Results
      for women were similar but most were not statistically significant. CONCLUSIONS:
      The exposure of healthy adults to passive smoking at work is related to
      utilisation of health care services and extra time off work. This results in
      costs to the health services, to employers and to those exposed.

PMID- 10942447
TI  - An epidemiological study of the relative importance of damp housing in relation
      to adult health.
AB  - STUDY OBJECTIVE: To examine the association between damp housing and adult
      health, taking into account a wide range of other factors that may influence
      health and could confound this relation. PARTICIPANTS AND SETTING: A general
      population sample of adults, aged 18-64, from Oxfordshire, Buckinghamshire,
      Berkshire and Northamptonshire. DESIGN: Secondary analysis of responses to a
      postal questionnaire survey carried out in 1997 with a 64% response rate (8889 of
      13 800). Housing dampness was assessed by self report. Health was measured by
      responses to a series of questions including presence of asthma and longstanding
      illness generally, use of health services and perceived health status (the SF
      36). The effect of damp was examined using the chi(2) test and one way analysis
      of variance. Significant associations with the various health outcomes were
      further explored taking into account 35 other housing, demographic, psychosocial
      and lifestyle variables using stepwise logistic and linear regression. MAIN
      RESULTS: Bivariate analyses indicated that damp was associated with the majority
      of health outcomes. Regression modelling however, found that being unable to keep
      the home warm enough in winter was a more important explanatory variable. Worry
      about pressure at work and to a lesser extent about money, showed an independent
      association with perceived health status equal to or greater than that of the
      housing environment, including cold housing, and that of health related
      lifestyles. CONCLUSIONS: This study shows that being unable to keep the home warm
      enough in winter is more strongly associated with health outcomes than is damp
      housing. However, as cold and damp housing are closely related, it is likely that
      their combined effects are shown in these results. The importance of worry as an
      independent predictor of health status needs testing in other studies. Its
      prevalence and relative importance suggest that it may be a significant
      determinant of public health.

PMID- 10942448
TI  - Trends in Belgian premature avoidable deaths over a 20 year period.
AB  - STUDY OBJECTIVES: To analyse over a 20 year period the level and trends in the
      "EC avoidable death indicators". DESIGN: The Years of Potential Life Lost (YPLL)
      method applied to curative and preventive avoidable mortality indicators in
      Belgium for four successive five year periods, countrywide as well as by
      district, separately for women and men. Ratios of YPLL rates (age standardised)
      describe changes between 1974-78 and 1990-94. SETTING: Belgium for the periods
      1974-78, 1980-84, 1985-89, 1990-94. PARTICIPANTS: All avoidable death cases aged
      1-64. MAIN RESULTS: Ratio of YPLL rates indicated a more favourable development
      between 1974-78 and 1990-94 in the EC avoidable indicators than in all causes
      premature mortality. The EC avoidable mortality indicators have been assigned to
      two categories, curative indicators and preventive indicators. The best ratio of
      YPLL rates was found in curative indicators for men but the largest gains in YPLL
      rates over the periods come from the "preventive indicators" in men. For women,
      malignant neoplasm of the breast rose to the first ranked in 1985-1989 and 1990
      1994, where it contributed to more years of YPLL loss than motor vehicle
      accidents, and malignant neoplasm of the trachea, bronchus and lung had risen to
      the fifth ranked since 1985-89. The order of the top causes for men did not
      change between 1974 and 1994, except for cirrhosis of liver, which rose from the
      fifth to the fourth rank. In the particular case of one "preventive indicator",
      malignant neoplasm of the trachea, bronchus and lung, the regional analysis of
      time trend between 1974-78 and 1990-94 showed more districts with a favourable
      development for both men and women in the Flemish region than in Wallonia.
      CONCLUSION: The YPLL method combined with the avoidable mortality indicators
      enabled us to compare the changes of curative and preventive EC avoidable
      indicators between 1974-78 and 1990-94. In the case of malignant neoplasm of the
      trachea, bronchus and lung, which is of major concern to the health promotion
      policies, changes over the periods have widened a "north/south" health contrast.

PMID- 10942449
TI  - Changes in cardiovascular risk factors in different socioeconomic groups: seven
      year trends in a Chinese urban population.
AB  - STUDY OBJECTIVE: To analyse trends in socioeconomic differences in cardiovascular
      disease risk factors among an urban Chinese population using educational
      attainment as the socioeconomic indicator. DESIGN: Population surveys with
      randomly selected independent samples were carried out in 1989 and in 1996.
      Educational attainment, blood pressure, body mass index, cigarette smoking and
      lack of leisure time physical activity were determined. SETTING: Urban areas of
      the city of Tianjin, China. PARTICIPANTS: A total of 14 275 respondents aged 25
      64 years. MAIN RESULTS: Diastolic blood pressure increased and the proportion of
      people without leisure time physical activity decreased in both sexes during the
      study period. The prevalence of smoking and the number of cigarettes smoked daily
      increased significantly among men. Smoking decreased in the least educated men
      and increased in those who had studied at least to college level. Body mass index
      decreased across all educational strata in women, but blood pressure increased in
      women with at least college level education. CONCLUSIONS: These data reveal a
      different picture in trends in the association of education and cardiovascular
      risk factors from those depicted in developed countries. This highlights the need
      for an effective intervention programme in the study population.

PMID- 10942451
TI  - Leadership for health. How can we ensure that the values and principles of public
      health become central to health and social policy?

PMID- 10942450
TI  - Cost and health consequences of reducing the population intake of salt.
AB  - STUDY OBJECTIVE: The aim was to estimate health and economic consequences of
      interventions aimed at reducing the daily intake of salt (sodium chloride) by 6 g
      per person in the Norwegian population. Health promotion (information campaigns),
      development of new industry food recipes, declaration of salt content in food and
      taxes on salty food/subsidies of products with less salt, were possible
      interventions. DESIGN: The study was a simulation model based on present age and
      sex specific mortality in Norway and estimated impact of blood pressure
      reductions on the risks of myocardial infarction and stroke as observed in
      Norwegian follow up studies. A reduction of 2 mm Hg systolic blood pressure
      (range 1-4) was assumed through the actual interventions. The cost of the
      interventions in themselves, welfare losses from taxation of salty
      food/subsidising of food products with little salt, cost of avoided myocardial
      infarction and stroke treatment, cost of avoided antihypertensive treatment,
      hospital costs in additional life years and productivity gains from reduced
      morbidity and mortality were included. RESULTS: The estimated increase in life
      expectancy was 1.8 months in men and 1.4 in women. The net discounted (5%) cost
      of the interventions was minus $118 millions (that is, cost saving) in the base
      case. Sensitivity analyses indicate that the interventions would be cost saving
      unless the systolic blood pressure reduction were less than 2 mm Hg, productivity
      gains were disregarded or the welfare losses from price interventions were high.
      CONCLUSION: Population interventions to reduce the intake of salt are likely to
      improve the population's health and save costs to society.

PMID- 10942452
TI  - Balkans briefing 6. Picking up the pieces: reflections on the initial stages of
      the reconstruction of the health care system in Kosovo, July 1999.

PMID- 10942453
TI  - Two and a half minutes with the president

PMID- 10942454
TI  - Management of menorrhagia in primary care-impact on referral and hysterectomy:
      data from the Somerset Morbidity Project.
AB  - OBJECTIVE: To investigate the management of menorrhagia in primary care and its
      impact on referral and hysterectomy rates. DESIGN: Prospective observational
      study. SETTING: 11 general practices from the Somerset Morbidity Project.
      SUBJECTS: 885 women consulting their general practitioner with menorrhagia over
      four years. MAIN OUTCOME MEASURES: Proportions of these women investigated and
      treated with drugs in primary care, referred to a gynaecologist and undergoing
      operative procedures. The relation between investigation and prescribing in
      primary care and referral to and surgery in secondary care. RESULTS: Less than
      half of women had a vaginal examination (42%, 95% CI 39% to 45%), or a full blood
      count (39%, 95% CI 36% to 43%). Almost a quarter of women, 23% (95% CI 20% to
      26%), received no drugs and 37% (95% CI 34% to 40%) received norethisterone. Over
      a third, 38% (95% CI 34% to 40%), of women were referred, and once referred 43%
      (95% CI 38% to 48%) of women were operated on. Women referred to a gynaecologist
      were significantly more likely to have received tranexamic acid and/or mefenamic
      acid in primary care (chi(2)=16.4, df=1, p<0.001). There were substantial between
      practice variations in management, for example in prescribing of tranexamic acid
      and/or mefenamic acid (range 16% to 72%) and referral to gynaecology (range 24%
      to 52%). There was a significant association between high referral and high
      operative rates (Spearman's correlation coefficient=0.86, p=0.001). CONCLUSIONS:
      Substantial differences in management exist between practices when investigating
      and prescribing for menorrhagia in primary care. Rates of prescribing of
      effective medical treatment remain low. The decision to refer a woman impacts
      markedly on her chances of subsequently being operated on. Effective management
      in primary care may not reduce referral or hysterectomy rates.

PMID- 10942455
TI  - Social and gender variation in the prevalence, presentation and general
      practitioner provisional diagnosis of chest pain.
AB  - OBJECTIVES: To describe the prevalence of Rose angina and non-exertional chest
      pain in men and women in socioeconomically contrasting areas; to describe the
      proportions of men and women who present with the symptom of chest pain and who
      receive a provisional general practitioner diagnosis of coronary heart disease;
      to assess the effects of gender and deprivation. DESIGN: Two random general
      population samples in socially contrasting areas were surveyed using the Rose
      angina questionnaire: the case notes of people identified with chest pain were
      reviewed. SETTING: Glasgow conurbation. PARTICIPANTS: 1107 men and women, aged 45
      64, with chest pain. OUTCOME MEASURES: Prevalence of Rose angina and non
      exertional chest pain; the proportions who had presented with chest pain and
      received a general practitioner's provisional diagnosis of coronary heart
      disease. RESULTS: There was no difference between social groups in the prevalence
      of all chest pain but a greater proportion of those in deprived groups had Rose
      angina and a greater proportion of these had the more severe grade. The
      proportion of people who had presented with chest pain was higher among
      socioeconomically deprived groups but there was no difference in the proportions
      receiving a general practitioner provisional diagnosis of coronary heart disease.
      Men were more likely to present with chest pain than women and were more likely
      to receive a provisional general practitioner diagnosis of coronary heart
      disease. CONCLUSIONS: No evidence was found of social differences in patient
      presentation or general practitioner diagnosis that might explain reported
      variations in uptake of cardiology services. In contrast, gender variation may
      originate in part from differences in patient presentation and general
      practitioner diagnosis. Further investigation of socioeconomic variations in
      uptake of cardiology services should focus later in the care pathway, on general
      practitioner referral patterns and clinical decisions taken in secondary care.

PMID- 10942456
TI  - Housing standards and excess winter mortality.

PMID- 10942457
TI  - Physicians should provide moral leadership to their communities: Presidential
      address.

PMID- 10942458
TI  - Amniotic fluid index values after preterm premature rupture of the membranes and
      subsequent perinatal infection.
AB  - OBJECTIVE: Our purpose was to determine whether an amniotic fluid index (AFI) <5
      cm after preterm premature rupture of the membranes is associated with an
      increased risk of perinatal infection. STUDY DESIGN: We performed a nonconcurrent
      prospective analysis of 225 singleton pregnancies complicated by preterm
      premature rupture of the membranes, with delivery between 24 and 32 weeks'
      gestation. All included patients received 2 doses of betamethasone antenatally,
      in the first 24 hours after admission, and broad-spectrum antibiotic prophylaxis.
      Patients were categorized into 2 groups on the basis of a 4-quadrant AFI <5 cm (n
      = 131) or > or =5 cm (n = 94). Perinatal outcomes analyzed included latency until
      delivery, mode of delivery, and frequencies of clinical chorioamnionitis,
      postpartum endometritis, and culture-proved early neonatal sepsis. Continuous
      data were evaluated for normal distribution and tested for significance with the
      Student t test. Categoric data were tested with the chi(2) and Fisher exact
      tests. Multiple logistic regression analyses were performed with
      chorioamnionitis, endometritis, and early-onset neonatal sepsis each as the
      dependent variable in separate analyses. All 2-sided P values <.05 were
      considered significant. RESULTS: Both groups were similar with respect to
      selected demographics, gestational age at rupture of the membranes, birth weight,
      and maternal group B streptococcal colonization. Patients with an AFI <5 cm
      demonstrated a shorter mean latency until delivery (5.5 +/- 4.0 vs 14.1 +/- 5.2)
      (mean +/- SD) days (P =.02), greater frequency of amnioinfusion therapy (23.6% vs
      5.3%) (P <.001), and cesarean delivery for nonreassuring fetal testing (18.3% vs
      4. 3%) (P =.01). Multiple logistic regression analysis showed that an AFI <5 cm
      was the only significant risk factor independently associated with early-onset
      neonatal sepsis (P =.004) and chorioamnionitis (P =.024). CONCLUSIONS: An AFI <5
      cm after preterm premature rupture of the membranes between 24 and 32 weeks'
      gestation is associated with an increased risk of perinatal infection and a
      shorter latency preceding delivery.

PMID- 10942459
TI  - The distribution of pelvic organ support in a population of female subjects seen
      for routine gynecologic health care.
AB  - OBJECTIVE: This study was undertaken to describe the distribution of pelvic organ
      support stages in a population of women seen at outpatient gynecology clinics for
      routine gynecologic health care. STUDY DESIGN: This was an observational study.
      Women seen for routine gynecologic health care at four outpatient gynecology
      clinics were recruited to participate. After informed consent was obtained
      general biographic data were collected regarding obstetric history, medical
      history, and surgical history. Women then underwent a pelvic examination. Pelvic
      organ support was measured and described according to the pelvic organ prolapse
      quantification system. Stages of support were evaluated by variable for trends
      with Pearson chi(2) statistics. RESULTS: A total of 497 women were examined. The
      average age was 44 years, with a range of 18 to 82 years. The overall
      distribution of pelvic organ prolapse quantification system stages was as
      follows: stage 0, 6.4%; stage 1, 43.3%; stage 2, 47.7%; and stage 3, 2.6%. No
      subjects examined had pelvic organ prolapse quantification system stage 4
      prolapse. Variables with a statistically significant trend toward increased
      pelvic organ prolapse quantification system stage were advancing age, increasing
      gravidity and parity, increasing number of vaginal births, delivery of a
      macrosomic infant, history of hysterectomy or pelvic organ prolapse operations,
      postmenopausal status, and hypertension. CONCLUSION: The distribution of the
      pelvic organ prolapse quantification system stages in the population revealed a
      bell-shaped curve, with most subjects having stage 1 or 2 support. Few subjects
      had either stage 0 (excellent support) or stage 3 (moderate to severe pelvic
      support defects) results. There was a statistically significant trend toward
      increased pelvic organ prolapse quantification system stage of support among
      women with many of the historically quoted etiologic factors for the development
      of pelvic organ prolapse.

PMID- 10942460
TI  - Accurate repair of the prolapsed vagina by use of measured lateral flaps.
AB  - OBJECTIVE: We report our experience with a technique for planning the final
      vaginal caliber and location of the vaginal apex in patients with severe vaginal
      prolapse. STUDY DESIGN: During the 2-year period ending April 1998, the technique
      was used in all 27 patients who were undergoing vaginal repair of prolapse
      performed by Mitchel S. Hoffman, MD, and who desired to retain the vagina but
      required at least partial excision. The major steps included determination of
      sites for lateral apical support, definition of the desired introital caliber,
      marking of the measured lateral vaginal flaps, excision of the intervening
      epithelium (and uterus if present, n = 14), high peritoneal closure, closure of
      the anterior vaginal wall, placement of apical supporting sutures, and completion
      of closure with tying of supporting sutures. Small flaps were designed for the 8
      patients who did not anticipate further sexual intercourse. RESULTS: The only
      intraoperative complication was hemorrhage >1000 mL in 3 patients. Immediate
      anatomic results were considered excellent for 26 patients. The only early
      postoperative complication was hemorrhage in a patient being treated with an
      anticoagulant; she responded to conservative management. Follow-up was available
      for 24 patients (21-42 months of follow-up; mean, 29 months). All patients had
      complete relief of prolapse symptoms. Anatomic results remained excellent for 21
      of the 24 patients; in the remaining 3 patients asymptomatic grade 2 cystoceles
      developed at 6 to 12 months. Three patients had new urinary symptoms that
      persisted. Nine patients resumed sexual intercourse, with no difficulties noted.
      CONCLUSION: Defining the vaginal apex and designing lateral vaginal flaps
      facilitate the precise creation of an anatomically and functionally appropriate
      vagina, with reasonable morbidity, good symptomatic relief, and mild alteration
      of surrounding organ function.

PMID- 10942461
TI  - Initial development of a system-wide maternal-fetal outcomes assessment program.
AB  - OBJECTIVE: This study was undertaken to develop a comprehensive risk-assessment
      approach capable of evaluating maternal and fetal outcomes. STUDY DESIGN: Data
      from 10,984 women and 11,066 infants delivered at 79 military treatment
      facilities in the United States from 1995 to 1997 were used to develop two
      individual but complementary risk-adjustment models for maternal and, separately,
      fetal outcomes. A range of maternal and delivery-related risk variables and
      clinically important outcomes were identified by expert opinion and selected and
      weighted with ordinal logistic regression analysis. Receiver operating
      characteristic curves for the maternal and fetal models were determined.
      Variation across the facilities in risk-adjusted performance was also evaluated.
      RESULTS: Risk factors and poor outcomes were rare for both mothers and infants,
      with 96.9% of infants and 97.7% of mothers having good or excellent outcomes
      (0.7% mortality and 0.01% mortality, respectively). Despite the low frequency of
      poor outcomes both models performed well, with receiver operating characteristic
      curves of 0.75 for maternal outcomes and 0.78 for infant outcomes. When the
      models were applied to the military treatment facilities, there were significant
      differences among facilities in risk-adjusted outcomes. Twenty-four of the
      facilities in the study (30%) had outcomes odds ratios that were significantly >1
      or significantly <1 (P <.05). There did not appear to be any relationship between
      the performance of a military treatment facility for maternal outcome and that
      for infant outcome. CONCLUSION: Complementary risk models for maternal and infant
      outcomes were developed that had satisfactory discriminatory power across a
      variety of facilities within a large health system. With further development and
      refinement this approach holds promise of being able to detect variations in risk
      adjusted performance that could be used to identify best practices. The results
      might also be used to help coordinate and improve the quality of care for the
      entire conception-to-delivery process.

PMID- 10942462
TI  - Ethical theory and principles: do they have any relevance to problems arising in
      everyday practice?
AB  - This review of ethical theories with application to two difficult obstetric cases
      will allow the practicing obstetrician and gynecologist to use these theories to
      help resolve difficult ethical dilemmas. In the first case a pregnant human
      immunodeficiency virus-infected woman refuses to take triple preventive therapy,
      with potential fetal harm. In the second case a couple with a quintuplet
      multifetal pregnancy needs assistance to decide about selective termination to
      effect fetal reduction.

PMID- 10942463
TI  - Optimal pregnancy outcome in a minimal-stimulation in vitro fertilization
      program.
AB  - OBJECTIVE: We sought to provide a cost-beneficial approach to in vitro
      fertilization for infertile patients who could not afford the standard treatment
      with in vitro fertilization and to determine the optimal level of minimal ovarian
      stimulation to achieve acceptable pregnancy rates. STUDY DESIGN: We performed a
      retrospective cohort study of 216 patients who underwent "minimal stimulation" in
      vitro fertilization between January 1994 and December 1998. During the first half
      of this study, various minimal ovarian stimulation protocols were performed in
      our private, free-standing center for in vitro fertilization. More recently, more
      ovarian stimulation, including a 4-day protocol featuring gonadotropin-releasing
      hormone agonist flare (ultrashort flare), was used. Clinical pregnancy outcome,
      multiple gestation, complications, and maternal age were compared between the
      first and second halves of this study. RESULTS: The average ages of patients in
      the first half (phase 1) and the second half (phase 2) were similar, 32.4 +/- 0.3
      versus 32.6 +/- 0.3 years, respectively. An average of 3.5 oocytes per retrieval
      was obtained in phase 1 versus 5.9 oocytes in phase 2. Failure to retrieve
      oocytes occurred in 3% of all cases. The mean number of embryos transferred per
      patient was 2.0 in phase 1 versus 2.4 in phase 2. In phase 1, 16.1% of patients
      failed to have viable embryos for transfer, in comparison with 9.7% in phase 2.
      The overall clinical pregnancy rate per retrieval was 16.9% in phase 1 versus 36.
      6% in phase 2. Multiple gestation occurred in 5.0% of clinical pregnancies in
      phase 1 but increased to 33% in phase 2, with 9 sets of twins and 6 sets of
      triplets. The implantation rate was 9.3% for phase 1 versus 23.3% for phase 2.
      The clinical pregnancy rates per retrieval for phase 2 patients were 41.6% in
      women < or =34 years old and 25.6% for those > or =35 years old. No case of
      ovarian hyperstimulation syndrome was noted. CONCLUSIONS: Minimal ovarian
      stimulation in the setting of in vitro fertilization offers a cost-beneficial
      alternative to standard treatment with in vitro fertilization in infertile
      patients who are <35 years old and in women <40 years old who have adequate
      oocyte reserve. More stimulation improves outcome. Minimalstimulation in vitro
      fertilization provides an alternative for those patients who cannot afford
      standard in vitro fertilization or who are concerned with exposure to high
      dosages of fertility medications.

PMID- 10942464
TI  - Does augmented growth impose an increased risk of fetal death?
AB  - OBJECTIVE: Our purpose was to examine the risk of fetal death associated with
      augmented fetal growth. STUDY DESIGN: All live births recorded in Virginia
      between January 1, 1991, and December 31, 1993, were examined. Mortality rates
      were examined for infants born at or beyond 24 weeks' gestational age with
      weights between the 75th and 90th percentiles, from the 90th to the 95th
      percentile, and >95th percentile. RESULTS: Mortality rates were found to rise
      only slightly with birth weights >90th percentile. A recorded diagnosis of
      maternal diabetes, however, was associated with a significant risk in the
      presence of augmented fetal growth. Augmented fetal growth without maternal
      glucose intolerance showed no increase in mortality. CONCLUSION: Augmented fetal
      growth in the absence of maternal glucose intolerance appeared not to be
      associated with a significant increase in the risk of death among these births.
      Increased risk was found when augmented fetal growth was associated with maternal
      diabetes.

PMID- 10942465
TI  - Fetal hydrolaparoscopy and endoscopic cystotomy in complicated cases of lower
      urinary tract obstruction.
AB  - OBJECTIVE: Vesicoamniotic shunting may be difficult or impossible in selected
      cases of fetal lower obstructive uropathy. The purpose of this article is to
      describe the performance of fetal hydrolaparoscopy and endoscopic fetal cystotomy
      in two fetuses with complicated lower obstructive uropathy. STUDY DESIGN: Fetal
      hydrolaparoscopy-endoscopic fetal cystotomy was performed in a patient with a
      markedly thickened bladder that could not be entered percutaneously. A
      peritoneoamniotic (bridge) shunt was also placed. Fetal hydrolaparoscopy
      endoscopic fetal cystotomy was performed in a second patient with a collapsed
      bladder from a previous vesicocentesis, because vesicoinfusion resulted in
      further ascites. Fetal cystoscopy was performed after endoscopic fetal cystotomy,
      and posterior urethral valves were ablated with neodymium:yttrium-aluminum-garnet
      laser energy. A vesicoamniotic shunt was left in place. RESULTS: Adequate bladder
      drainage was obtained in both cases. The first baby required bilateral nephrotomy
      and a permanent cystotomy at birth and is scheduled for a bladder expansion
      procedure at the age of year. The second patient had premature rupture of
      membranes and fetal death from treatment of this complication 5 days after the
      original procedure. CONCLUSION: Fetal hydrolaparoscopy-endoscopic fetal cystotomy
      can be performed in complicated cases of lower obstructive uropathy. The
      procedure involves the creation of a defect in the bladder dome under direct
      endoscopic visualization within a spontaneous or intentional hydroperitoneum.
      Peritoneoamniotic shunting, vesicoamniotic shunting, or ablation of posterior
      urethral valves may then be performed. Fetal hydrolaparoscopy-endoscopic fetal
      cystotomy should be reserved only for complicated cases of lower obstructive
      uropathy in which conventional vesicoamniotic shunting is not safely possible.
      Further experience with fetal hydrolaparoscopy-endoscopic fetal cystotomy is
      necessary to establish its risks and benefits.

PMID- 10942466
TI  - Sexually transmitted infection and teenage sexuality.
AB  - The twin epidemics of sexually transmitted infection and nonmarital pregnancy and
      their consequences are two of the most significant issues faced by Americans
      today. Approximately 900,000 teenagers become pregnant each year. Research
      indicates that these pregnancies often limit future educational and economic
      opportunities for mother, father, and child. Sexually transmitted infections also
      pose a major threat to adolescents. For example, during a 3-year study of
      sexually active women at a major university, 60% were infected with human
      papillomavirus. Research indicates that adolescents, especially female ones, are
      physically more susceptible to sexually transmitted infections than adults. There
      have been a number of attempts by the medical and public health communities to
      confront these problems. In fact, the most popular strategy of the past 15 years
      has relied on increasing contraceptive use. For reduction of sexually transmitted
      infections, this approach depends on condoms, and for reduction of pregnancy, on
      oral contraceptives. The problem with condom-based approaches, however, is that
      physicians are often unaware of the limitations in the protection provided by
      condoms from sexually transmitted infections. For example, condoms offer
      inadequate protection from 3 of the most common sexually transmitted infections
      human papillomavirus, type 2 herpesvirus, and chlamydia. By helping adolescents
      delay their sexual debut, we can offer hope to the greatest number of teens.
      Physicians can take the lead in emphasizing this approach both with their
      patients and in their medical organizations.

PMID- 10942467
TI  - Detection of Neisseria gonorrhoeae and Chlamydia trachomatis colonization of the
      gravid cervix.
AB  - OBJECTIVES: The aims of the study were to determine whether a Gram stain of
      cervical mucus can accurately rule out infection with Neisseria gonorrhoeae or
      Chlamydia trachomatis and to compare a diagnostic test that is based on the
      polymerase chain reaction with a deoxyribonucleic acid probe in the detection of
      these organisms. STUDY DESIGN: Gravid patients were screened for N gonorrhoeae
      and C trachomatis with a deoxyribonucleic acid probe, Gram stain, and analysis
      with the polymerase chain reaction. A normal, noninfected sample was defined by
      <10 polymorphonuclear leukocytes per high-power field on the Gram stain. Standard
      statistical methods were used to compare results of the Gram stain and the
      deoxyribonucleic acid probe, as well as to compare results of deoxyribonucleic
      acid probe hybridization and polymerase chain reaction analysis. A P value of
      <.05 was considered statistically significant. RESULTS: Patient enrollment
      totaled 519. The prevalence of infection as determined by deoxyribonucleic acid
      probe hybridization was 1.4% for N gonorrhoeae (7/518) and 6.8% for C trachomatis
      (35/518). The cervical Gram stain predicted the absence of infection in 17%
      (90/518) of patients, with a negative predictive value of 99% for N gonorrhoeae
      and 97% for C trachomatis. African American race, age <20 years, and unmarried
      status were all predictors of the presence of C trachomatis or N gonorrhoeae
      cervicitis. For the patients who lacked these risk factors (n = 74), the Gram
      stain had 100% negative predictive value. Analysis with the polymerase chain
      reaction detected 8 additional patients with C trachomatis and 105 additional
      patients with N gonorrhoeae, in comparison with deoxyribonucleic acid probe
      hybridization. CONCLUSION: The cervical Gram stain can accurately predict the
      absence of N gonorrhoeae and C trachomatis in gravid women. Analysis with the
      polymerase chain reaction indicates that N gonorrhoeae and C trachomatis are
      significantly more prevalent in this population than previously reported.

PMID- 10942468
TI  - Vaginal infections in human immunodeficiency virus-infected women.
AB  - OBJECTIVE: This study was undertaken to compare the frequencies of vaginal
      infections among human immunodeficiency virus-infected women with those among
      human immunodeficiency virus-seronegative women. STUDY DESIGN: Human
      immunodeficiency virus-seropositive women attending a comprehensive care center
      for human immunodeficiency virus disease at the outpatient department of an inner
      city hospital in Houston underwent rigorous gynecologic evaluation for sexually
      transmitted diseases, including evidence of vaginal infections such as bacterial
      vaginosis, vulvovaginal candidiasis, and trichomonal vaginitis. Demographic
      information was collected, as was information regarding disease classification
      and degree of immunosuppression. Data regarding sexually transmitted diseases,
      data regarding vaginal infections, and demographic information were collected
      from a cohort of human immunodeficiency virus-seronegative women attending a
      sexually transmitted disease and family planning clinic at the same institution.
      The two groups were compared to determine whether there were any differences
      between them in the frequencies of sexually transmitted diseases and vaginal
      infection. Data analysis used the t test for parametric data and the Fisher exact
      test for nonparametric data where appropriate. P <.05 was considered significant.
      Statistical analysis was performed with the SAS (SAS Institute, Inc, Cary, NC)
      statistical software package. RESULTS: There was no difference in age between the
      2 groups. The human immunodeficiency virus-infected group was predominantly
      African American (80.5%), whereas the human immunodeficiency virus-seronegative
      control group was more evenly divided between African American women (45.8%) and
      Latinos (41.7%; P <.0001). Although there was no significant association between
      HIV infection and sexually transmitted diseases in general, there were
      significant associations between human immunodeficiency virus infection and
      bacterial vaginosis (P =.02), vulvovaginal candidiasis (P =.001), and trichomonal
      vaginitis (P =. 003). CONCLUSION: Human immunodeficiency virus-infected women had
      increased frequencies of vaginal infections, including bacterial vaginosis,
      vulvovaginal candidiasis, and trichomonal vaginitis, with respect to human
      immunodeficiency virus-seronegative control subjects. No differences between the
      2 groups were seen in the frequencies of sexually transmitted diseases.

PMID- 10942469
TI  - Should intravenous tocolysis be considered beyond 34 weeks' gestation?
AB  - OBJECTIVE: Our purpose was to assess the incidence of respiratory distress
      syndrome in nonindigent women with uncomplicated preterm labor between 34 and 36
      weeks' gestation. STUDY DESIGN: All women seen between June 1, 1992, and April
      15, 1999, with uncomplicated preterm labor and intact membranes and delivering
      between 34 and 36 weeks' gestation were analyzed. Rates of respiratory distress
      syndrome after delivery were calculated. A chi(2) analysis was performed, and a P
      value of <.05 was considered statistically significant. RESULTS: Respiratory
      distress syndrome was noted in 8 (17.4%) of 46 infants delivered at 34 weeks'
      gestation, in comparison with 5 (6.3%) of 80 infants and 7 (4.2%) of 165 infants
      delivered at 35 and 36 weeks' gestation, respectively (P =.008). The rate of
      respiratory distress syndrome after delivery at 34 weeks was significantly higher
      than at 35 weeks (P =.048). CONCLUSION: The rate of respiratory distress syndrome
      after delivery at 34 weeks is significantly higher than at either 35 or 36 weeks'
      gestation in our population.

PMID- 10942470
TI  - A comparison of visual analyses of intrapartum fetal heart rate tracings
      according to the new national institute of child health and human development
      guidelines with computer analyses by an automated fetal heart rate monitoring
      system.
AB  - OBJECTIVES: The aim of this study was to compare the visual analyses of fetal
      heart rate tracings by observers according to recent National Institute of Child
      Health and Human Development interpretative guidelines both with each other and
      with those of a computerized fetal heart rate analysis and alerting system. STUDY
      DESIGN: One-hour sections of intrapartum fetal heart rate records were analyzed
      by a computerized monitoring system (Hewlett-Packard TraceVue; HP GmbH,
      Boblingen, Germany) and by 4 observers (a registered obstetric nurse, a certified
      nurse-midwife, an obstetrics resident physician, and a physician maternal-fetal
      medicine faculty member) instructed to use the new National Institute of Child
      Health and Human Development guidelines. We compared specific alerts, baseline
      rates, frequencies of accelerations and decelerations, and signal quality
      assessments generated by the TraceVue system and the observers. Power analysis
      indicated that 50 tracings were required to detect interobserver and observer
      computer agreement levels of 80% +/- 10%. Statistical comparisons used kappa
      coefficient, chi(2) test, and analysis of variance with repeated measures as
      appropriate. RESULTS: Levels of agreement between observer pairs and the computer
      did not vary significantly across successive 10-minute intervals. Overall levels
      of interobserver agreement for baseline rate, tracing quality assessment,
      frequencies of accelerations and decelerations, and alerts ranged from 45% to 99%
      and were highest for baseline rate and signal loss and lowest for acceleration
      and deceleration counts. Interobserver agreement for alerts was relatively high
      (range, 72%-84%), with virtually no difference between any of the observers and
      the computer (range, 76.9%-79.2%; kappa = 0.25). CONCLUSION: Use of the National
      Institute of Child Health and Human Development guidelines for visual fetal heart
      rate interpretation did not increase agreements on most fetal heart rate features
      beyond those expected by chance or noted in previous reports. These guidelines
      did appear to blunt some interpretive differences, possibly as a result of
      observer background. Although levels of agreement on fetal heart rate features
      differed, agreements on clinical alerts were similar among all observers and a
      computerized fetal heart rate monitoring system. Computer analysis of fetal heart
      rate tracings could eliminate interobserver variation that results from visual
      analysis and could produce more consistent clinical responses to normal and
      abnormal fetal heart rate patterns.

PMID- 10942471
TI  - Cauterization of hydrosalpinges before in vitro fertilization is an effective
      surgical treatment associated with improved pregnancy rates.
AB  - OBJECTIVE: Our purpose was to determine whether proximal tubal cauterization is
      an effective method of reversing the decreased pregnancy rates seen in patients
      undergoing in vitro fertilization-embryo transfer with hydrosalpinges present.
      STUDY DESIGN: We studied a group of 94 patients with tubal factor infertility.
      Sixty patients had hydrosalpinges documented by either hysterosalpingography or
      laparoscopy, or both. Forty-five had surgical treatment of hydrosalpinges by
      salpingectomy or by proximal tubal cauterization. In vitro fertilization-embryo
      transfer was performed within 3 months after surgery. Pregnancy and implantation
      rates were compared. RESULTS: Patients with hydrosalpinx had significantly
      decreased clinical pregnancy and implantation rates per cycle (14% and 8%,
      respectively) compared with those of patients undergoing proximal tubal
      cauterization before the in vitro fertilization cycle (73% and 36%,
      respectively). These pregnancy and implantation rates are comparable with those
      found in patients with tubal factor infertility without hydrosalpinges (53% and
      22%, respectively), as well as in salpingectomy-treated patients (46% and 24%,
      respectively). CONCLUSIONS: Proximal tubal cauterization is effective in
      reversing the adverse effects of hydrosalpinges.

PMID- 10942472
TI  - Late third-trimester treatment of rectovaginal group B streptococci with
      benzathine penicillin G.
AB  - OBJECTIVE: We sought to determine the efficacy of late third-trimester benzathine
      penicillin G administration in eradicating maternal group B streptococcal
      colonization at delivery. STUDY DESIGN: We performed a prospective trial of late
      third-trimester treatment with benzathine penicillin G versus observation in 78
      obstetric patients colonized with group B streptococci. Patients were screened by
      use of rectovaginal swabs cultured in selective media between 34 and 37 completed
      weeks' gestation. Patients with positive cultures were offered antepartum
      treatment with 4.8 million units of intramuscular benzathine penicillin G or
      observation. Participants in both groups were recultured at their delivery
      admission before receiving standard intrapartum therapy. The primary outcome was
      the frequency of persistent maternal group B streptococcal colonization at the
      delivery admission. Other outcome variables included semiquantitative growth
      characteristics of all group B streptococcal cultures, the frequency of neonatal
      sepsis, and adverse maternal effects. Data were analyzed by the Student t test
      for continuous variables and the chi(2) or Fisher exact test for categoric
      variables, with significance established at P <.05. RESULTS: Both groups were
      similar with respect to selected demographics, gestational age at delivery, and
      frequency of heavy group B streptococcal growth in initial screening cultures.
      The mean interval from treatment until delivery was 19.4 +/- 7.5 days (mean +/-
      SD). There were no cases of neonatal sepsis in either group or any adverse
      maternal effects attributed to the treatment. Group B streptococcal culture
      characteristics at delivery admission were as follows. Positive results for group
      B streptococci were found in 7 (25%) treated patients and 41 (82%) patients under
      observation (relative risk, 0.30; 95% confidence interval, 0.16-0.59; P <.0001).
      Positive results for heavy growth of group B streptococci were found in 0 (0%)
      treated patients and 31 (62%) patients under observation (relative risk, 0.01;
      95% confidence interval, 0.00-0.12; P <.0001). CONCLUSIONS: Treating group B
      streptococci carriers with benzathine penicillin G in the late third trimester
      eradicates or significantly reduces maternal group B streptococcal colonization
      at delivery. This may provide an adjuvant therapy to those mothers at risk for
      receiving inadequate intrapartum antibiotic prophylaxis against group B
      streptococci.

PMID- 10942473
TI  - Blastocyst transfer: a useful tool for reduction of high-order multiple
      gestations in a human assisted reproduction program.
AB  - OBJECTIVE: We evaluated the efficacy of blastocyst transfer in decreasing the
      incidence of high-order multiple gestations after in vitro fertilization. STUDY
      DESIGN: We conducted a retrospective analysis of 218 patients who were undergoing
      in vitro fertilization and by our criteria of three 8-cell embryos on day 3 could
      receive either a day 3 transfer of cleaved embryos or a day 5 transfer of
      blastocysts. Ongoing pregnancy rates, implantation rates (determined by the total
      number of visualized gestational sacs), and multiple pregnancy rates were
      compared between the 2 groups. RESULTS: Respective day 3 and day 5 ongoing
      pregnancy rates (61% and 51%) and implantation rates (35% and 33%) were not
      significantly different. There were 9 triplet or higher gestations in the day 3
      group and 0 in the day 5 group. CONCLUSION: Blastocyst transfer can be used to
      reduce the number of embryos transferred and the resultant incidence of high
      order multiple pregnancies while maintaining high pregnancy rates.

PMID- 10942474
TI  - Two-stage cervical cancer screening: an alternative for resource-poor settings.
AB  - OBJECTIVE: We sought to introduce 2-stage cervical cancer screening in which 2
      screening tests are performed sequentially (the second test is performed only if
      the first result is positive), followed by treatment if both test results are
      abnormal. STUDY DESIGN: A total of 1423 women from Cape Town, South Africa, were
      screened by direct visual inspection, human papillomavirus deoxyribonucleic acid
      testing, cytologic testing, and cervicography. If an abnormality was identified
      with any test, women were referred for colposcopy. RESULTS: Direct visual
      inspection, cytologic testing, human papillomavirus deoxyribonucleic acid
      testing, and cervicography, when used alone, identified 24, 26, 23, and 23 cases
      of disease (high-grade squamous intraepithelial lesion or cancer) per 1000 women,
      respectively, and would classify 182, 71, 137, and 112 women without disease as
      having abnormal results. Two-stage screening with direct visual inspection first,
      followed by cytologic testing, human papillomavirus deoxyribonucleic acid
      testing, or cervicography, would detect 18, 16, and 18 cases per 1000 women,
      respectively, and would substantially reduce the number of women without disease
      who were classified as having abnormal results. CONCLUSION: Two-stage screening
      for cervical cancer provides an attractive alternative to conventional screening
      for low-resource settings.

PMID- 10942475
TI  - Oral contraceptive use and glucose metabolism in a national sample of women in
      the united states.
AB  - OBJECTIVE: This study was undertaken to determine whether users of oral
      contraceptives in a nationally representative population of US women had elevated
      levels of measures of glucose metabolism. STUDY DESIGN: Cross-sectional data from
      the Third National Health and Nutrition Examination Survey (1988-1994) included
      hemoglobin A(1c) levels and fasting glucose, insulin, and C-peptide levels. Means
      were compared among those who had never used oral contraceptives, current users
      of oral contraceptives, and former users of oral contraceptives, with and without
      adjustment for potential confounders. RESULTS: The vast majority of current users
      of oral contraceptives were using low-dose estrogen formulations. The two most
      common preparations were a triphasic formulation containing 0. 035 mg ethinyl
      estradiol and 0.5, 0.75, and 1 mg norethindrone (23. 9%) and a monophasic
      formulation containing 0.035 ethinyl estradiol and 1 mg norethindrone (20.7%).
      Current users of oral contraceptives did not have elevated values for any of the
      four measures of glucose metabolism. Hemoglobin A(1c) level and fasting glucose,
      insulin, and C-peptide levels were not related to duration of current use, age at
      which use began, or major formulation type. Among women who were former users of
      oral contraceptives there was no evidence of higher values among those who had
      recently ceased use. CONCLUSION: Oral contraceptive formulations currently
      available in the United States are not associated with an adverse glucose
      metabolic profile.

PMID- 10942476
TI  - Utility of bipolar electrocautery scissors for abdominal hysterectomy.
AB  - OBJECTIVE: This was an evaluation of usefulness of bipolar electrocautery
      scissors for abdominal hysterectomy. STUDY DESIGN: Fifty women with uterine
      fibromatosis underwent abdominal hysterectomy: 25 randomly selected patients were
      operated on with conventional technique and the other 25 patients were operated
      on with bipolar electrocautery scissors. In both groups operating time, number of
      ligations, and blood loss were assessed. Data were compared by analysis of
      variance and chi(2) test as appropriate. RESULTS: In the bipolar group the
      average operating time was 25% shorter than in the conventional group (P <.01),
      and the number of ligations and the amount of blood loss were significantly
      reduced (P <.01). There was no increase in the complication rate. CONCLUSIONS:
      Bipolar electrocautery scissors were confirmed to be safe and useful for open
      surgery by reducing the operating time and blood loss without increasing
      postoperative morbidity. Thus their use would lower the cost of surgery.

PMID- 10942477
TI  - An appraisal of screening for maternal type-specific herpes simplex virus
      antibodies to prevent neonatal herpes.
AB  - Almost all neonatal herpes simplex virus infections occur as a result of first
      episode maternal infection during late pregnancy when delivery occurs before the
      development of protective maternal antibodies. Screening of pregnant women for
      the presence of type-specific herpes simplex virus antibodies has therefore been
      suggested as a means of identifying women vulnerable to herpes simplex virus
      acquisition and subsequent transmission of herpes simplex virus to their
      neonates. Couples in whom herpes simplex virus serotype discordance is identified
      could be counseled regarding sexual behavior modification to avoid maternal
      herpes simplex virus infection. However, the ramifications of routine screening
      for herpes simplex virus susceptibility during pregnancy could be profound in
      terms of costs, prenatal care delivery, and even social duress. The recent US
      Food and Drug Administration approval of type-specific herpes simplex virus
      antibody assays for clinical use lends temporal urgency to the need for a
      critical examination of the relevant data. After we performed such an evaluation
      and created a decision analysis model to assess the potential cost-effectiveness
      of herpes simplex virus antibody screening, we concluded that screening for
      maternal type-specific herpes simplex virus antibodies cannot be recommended to
      prevent neonatal herpes.

PMID- 10942478
TI  - Cervical cancer practice patterns and appropriateness of therapy.
AB  - OBJECTIVE: This study was undertaken (1) to describe practice patterns for
      treatment of cervical cancer on a national scale, including patient
      characteristics associated with receiving appropriate versus inappropriate
      therapy, and (2) to determine whether mortality rate differences exist between
      patients who were treated appropriately and those who were treated
      inappropriately. STUDY DESIGN: We defined treatment appropriateness in cases of
      cervical cancer according to general recommendations for therapy for each
      International Federation of Gynecology and Obstetrics stage. In an analysis of
      data obtained from the Surveillance, Epidemiology, and End Results Program for
      1988 through 1994 we determined the associations of patient demographic
      characteristics and tumor characteristics with treatment appropriateness. The
      association between treatment appropriateness and overall mortality for as long
      as 7 years of follow-up was adjusted for age; marital status; Surveillance,
      Epidemiology, and End Results Program location; International Federation of
      Gynecology and Obstetrics stage of disease; lymph node status; tumor grade; and
      histologic classification. RESULTS: Overall 90% of all patients were found to
      have received appropriate therapy. Important variables significantly associated
      with being treated inappropriately versus appropriately included age <40 years,
      positive nodal status, and International Federation of Gynecology and Obstetrics
      stage IB disease. Important variables significantly associated with receiving no
      therapy versus receiving appropriate therapy were age >/=60 years, International
      Federation of Gynecology and Obstetrics stage IV disease, positive nodal status,
      and unknown nodal status. In a comprehensive model that included demographic
      factors and tumor characteristics, the adjusted hazard ratio for mortality among
      patients who were treated inappropriately versus appropriately was 0.87 (95%
      confidence interval, 0.70-1.09). The adjusted hazard ratio for mortality among
      patients who did not receive therapy versus those who were treated appropriately
      was 2.92 (95% confidence interval, 2.44-3.48). CONCLUSIONS: In an analysis of
      data from a tumor registry, cervical cancer practice patterns were generally
      found to follow accepted treatment guidelines. Appropriateness of therapy did not
      vary widely according to demographic variables. Although patients who received no
      therapy had an elevated risk of death with respect to that of patients who were
      treated appropriately, patients who were treated inappropriately had a mortality
      rate similar to that among those who were treated appropriately (perhaps because
      of limitations in Surveillance, Epidemiology, and End Results Program data).
      Results of this preliminary study suggest a need for further research on
      effectiveness of cervical cancer therapies in the general population.

PMID- 10942479
TI  - Estrogen replacement in perimenopause-related depression: a preliminary report.
AB  - OBJECTIVES: We examined the efficacy of estrogen in the treatment of depression
      in perimenopausal women with and without hot flushes. STUDY DESIGN: Women with
      perimenopause-related depression were randomized in a double-blind parallel
      design to receive either 17beta-estradiol or placebo for 3 weeks. Subsequently,
      women receiving estradiol during the first 3 weeks continued receiving estradiol
      for an additional 3 weeks, whereas women who had received placebo crossed over to
      estradiol for 3 weeks. Outcome measures included standardized mood rating scales
      and a visual analog scale self-report instrument. RESULTS: Of 34 female subjects,
      16 received estradiol first and 18 received placebo first. After 3 weeks of
      estradiol, standardized mood rating scale scores and visual analog scale symptom
      scores (eg, sadness, anhedonia, and social isolation) were significantly
      decreased compared with baseline scores (P <.01) and were significantly lower
      than scores in women receiving placebo (P <.01), who showed no significant
      improvement. Neither the presence of hot flushes nor the duration of treatment (3
      weeks vs 6 weeks) influenced outcome. A full or partial therapeutic response was
      seen in 80% of subjects receiving estradiol and 22% of those receiving placebo.
      CONCLUSION: In this preliminary study estradiol replacement effectively treats
      perimenopausal depression independent of its salutary effects on vasomotor
      symptoms.

PMID- 10942480
TI  - Pregnancies after reconstructive surgery for congenital cervicovaginal atresia.
AB  - Eighteen women aged 12 to 20 years with congenital cervicovaginal atresia were
      treated with a new technique of surgical canalization. All are now having regular
      menses. Two pregnancies have been achieved, with delivery of viable neonates.
      Surgical correction of this anomaly during adolescence may aid in restoration of
      menstrual and reproductive function.

PMID- 10942481
TI  - Fetal response to maternally administered morphine.
AB  - OBJECTIVE: We sought to determine the effects of maternally administered morphine
      on fetal response. STUDY DESIGN: Singleton pregnancies requiring fetal blood
      sampling were enrolled. Only study patients were given morphine intramuscularly.
      Maternal vital signs, fetal heart rate, biophysical profile score, and umbilical
      artery Doppler indices (systolic/diastolic ratio, resistance index, and
      pulsatility index) were completed before and after fetal blood sampling. Maternal
      and cord blood morphine concentrations were measured. RESULTS: Ten study and 6
      control patients were enrolled. A significantly lower biophysical profile score
      was observed in study patients (P =.001) as a result of absent fetal breathing
      movements and nonreactive nonstress tests. Gross and fine fetal movements were
      unaffected. A significant correlation was measured between the biophase morphine
      concentration and each of the Doppler indices. CONCLUSION: Morphine administered
      to the mother causes a significant decrease in the biophysical profile score.
      Correlation between the biophase morphine concentration and the Doppler indices
      was calculated. These results suggest that morphine acts as a vasoconstrictor of
      the placental vasculature but do not support the use of intramuscular morphine to
      suppress fetal movement.

PMID- 10942482
TI  - Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous
      abortion.
AB  - OBJECTIVE: This study was undertaken to investigate a possible link between first
      trimester diagnosis of bacterial vaginosis and cessation of pregnancy at < or =20
      weeks' gestation. STUDY DESIGN: Women (n = 228) who received routine prenatal
      care in Flanders, Belgium, during the first trimester (14 weeks' gestation) and
      had a living singleton fetus were examined for microbiologic flora of the vagina.
      Bacterial vaginosis was assessed either clinically (Amsel et al criteria),
      microscopically (clue cells), or by culture of bacterial vaginosis-associated
      bacteria. Data were analyzed univariately (relative risk) and multivariately.
      RESULTS: The presence of bacterial vaginosis at the first prenatal visit was
      strongly associated with subsequent early pregnancy loss (relative risk, 5.4; 95%
      confidence interval, 2.5-11). After multivariate analysis bacterial vaginosis,
      Mycoplasma hominis, and Ureaplasma urealyticum but not other microorganisms
      remained associated with an increased risk of miscarriage. CONCLUSION: Bacterial
      vaginosis and mycoplasmas may play causative roles in spontaneous abortion and
      early pregnancy loss.

PMID- 10942483
TI  - Graphic analysis of actively managed labor: prospective computation of labor
      progress in 500 consecutive nulliparous women in spontaneous labor at term.
AB  - OBJECTIVE: Active management has been shown to shorten the length of labor and
      reduce the incidence of prolonged labor. We examined the influence of this
      protocol on the rate of cervical dilatation by calculating a mean partogram to
      explain how this acceleration is achieved. STUDY DESIGN: We retrospectively
      analyzed partograms of cervical dilation in 500 consecutive nulliparous women in
      spontaneous labor at term with a singleton fetus in a cephalic presentation;
      cesarean deliveries were not excluded. Mean cervical dilations at admission and
      mean time intervals to reach 2, 3, 4, 6, 8, and 10 cm of dilatation and delivery
      were calculated, with 95% confidence intervals, both for the whole cohort and
      specifically in women with cervical dilatations <3 cm at admission. These data
      were used to construct mean partograms. RESULTS: The mean duration of labor was
      6.1 hours. The mean cervical dilatation at admission was 1. 7 cm; all but 2.8%
      were delivered within 12 hours. The cesarean rate was 5.4%. The mean partogram,
      with narrow 95% confidence intervals, shows a rapid active phase after a much
      shorter latent phase than reported in other analyses of labor. CONCLUSION: Active
      management reduces the duration of first labor mainly by shortening the latent
      phase in association with amniotomy at very early cervical dilatations and does
      not delay the diagnosis of labor until the active phase has begun.

PMID- 10942484
TI  - Risk factors for adverse maternal outcomes among women with HELLP (hemolysis,
      elevated liver enzymes, and low platelet count) syndrome.
AB  - OBJECTIVE: This study was undertake to determine risk factors for adverse
      maternal outcomes among women with HELLP (hemolysis, elevated liver enzymes, and
      low platelet count) syndrome. STUDY DESIGN: Maternal medical records of
      pregnancies complicated by HELLP syndrome managed between July 1, 1992, and April
      30, 1999, were reviewed. Risk factors evaluated included maternal age, parity,
      race, previous preeclampsia, chronic hypertension, gestational age at diagnosis,
      mean arterial blood pressure, nadir blood platelet count (<50,000 cells/microL vs
      > or =50,000 cells/microL), and peak serum levels of aspartate aminotransferase
      and lactate dehydrogenase. Maternal outcome variables analyzed included
      eclampsia, abruptio placentae, disseminated intravascular coagulopathy, pulmonary
      edema, pleural effusion, ascites, acute renal failure, liver hematoma, need for
      transfusion of blood products, cesarean delivery, and death. Statistical analysis
      was performed with the Student t test, the chi(2) test, and logistic regression
      analysis. RESULTS: A total of 183 women with HELLP syndrome were studied.
      Eclampsia was present in 6%, abruptio placentae was present in 10%, and
      disseminated intravascular coagulopathy was present in 8%. Forty-one women (22%)
      required transfusion of blood products. Incidence of eclampsia significantly
      decreased with increasing gestational age, from 16% at < or =28 weeks' gestation
      to 3% at >32 weeks' gestation (P <.05) and was higher among African American
      patients than among white patients (12% vs 3%; P <.05). Logistic regression
      analysis showed an independent relationship between eclampsia and race (P <.05).
      Incidence of abruptio placentae was higher among women with previous preeclampsia
      than among women without this clinical history (26% vs 5%; P <.05). Disseminated
      intravascular coagulopathy was significantly associated with abruptio placentae
      (P <.0001) and acute renal failure (P <.0001). A nadir platelet count of <50,
      000/microL, a peak serum aspartate aminotransferase level of >150 U/L, and a peak
      serum lactate dehydrogenase level of >1400 U/L were not independent risk factors
      for adverse outcome. CONCLUSIONS: Among women with HELLP syndrome, African
      American race is a risk factor for eclampsia. Both acute renal failure and
      abruptio placentae are associated with disseminated intravascular coagulopathy.
      Laboratory parameters of HELLP syndrome are not independent risk factors for
      adverse maternal outcome.

PMID- 10942485
TI  - Estrogen augments the vasodilatory effects of vascular endothelial growth factor
      in the uterine circulation of the rat.
AB  - OBJECTIVE: Pregnancy augments uterine artery vasodilatation in response to
      vascular endothelial growth factor, although the underlying mechanism is not
      known. The aim of this study was to test the hypothesis that estrogen and
      progesterone, the primary sex steroids of pregnancy, are responsible for this
      effect through increased endothelial secretion of nitric oxide. STUDY DESIGN:
      Adult female Sprague-Dawley rats underwent oophorectomy at 9 weeks of age with
      concomitant placement of 21-day timed-release pellets containing either 17beta
      estradiol (n = 6) or progesterone (n = 6), or a combination of these (n = 6).
      Control rats also underwent oophorectomy but did not receive hormone replacement
      (n = 6). Two to 3 weeks after oophorectomy the rats were killed and the main
      uterine artery was dissected free, cannulated in an arteriograph, and pressurized
      to 50 mm Hg. After constriction with phenylephrine, concentration-response curves
      to vascular endothelial growth factor (0.1-20 nmol/L) were performed to compare
      arterial sensitivity to and maximal effects of vascular endothelial growth factor
      among the 4 treatment groups. Vessels were then treated with N omega-nitro-L 
      arginine (0.24 mmol/L), an inhibitor of nitric oxide synthase, and the maximally
      effective concentration of vascular endothelial growth factor was reapplied to
      evaluate the relative contribution of nitric oxide to the overall effect.
      RESULTS: Comparisons of the effective concentration of vascular endothelial
      growth factor that elicited 50% of the maximal dilatation revealed the vessels of
      the estrogen group to be approximately 10 times more sensitive than the control
      group (0.4 +/- 0.11 nmol/L vs 4.2 +/- 1.13 nmol/L, respectively; P <. 05).
      Responses of vessels from the progesterone and combined groups were intermediate
      (progesterone, 2.3 +/- 0.66 nmol/L; combined, 1.1 +/- 0.28 nmol/L). Maximal
      vasodilatory responses were greatest in the groups with treatment including
      estrogen (estrogen, 61% +/- 3. 1%; combined, 54% +/- 3.4%; progesterone, 42% +/-
      5.8%, control, 40% +/- 3.5%; P <.05). Addition of N omega-nitro-L -arginine
      inhibited maximal vascular endothelial growth factor-induced dilatation by
      approximately 40% irrespective of treatment group. CONCLUSION: The presence of
      estrogen rather than progesterone leads to an enhancement of vascular endothelial
      growth factor-induced arterial dilatation during pregnancy. This effect results
      from a proportional increase in endothelial nitric oxide secretion, along with
      that of another, as yet unidentified vasodilatory substance.

PMID- 10942486
TI  - Triplets: outcomes of expectant management versus multifetal reduction for 127
      pregnancies.
AB  - OBJECTIVE: Our purpose was to compare outcomes of women with triplet gestations
      conceived via assisted reproductive technology who chose expectant management or
      multifetal pregnancy reduction. STUDY DESIGN: We performed a retrospective review
      of all women who initiated assisted reproductive technology cycles from August
      1995 through July 1997 with ultrasonographic documentation of triplets exhibiting
      fetal heart tones at 9 weeks of gestation (N = 127). Patients were then uniformly
      referred to a maternal-fetal medicine specialist and to 3 centers offering
      multifetal pregnancy reduction. RESULTS: Thirty-six percent of patients (46/127)
      chose multifetal pregnancy reduction with 95% undergoing reduction to twins. In
      the expectant management group, 13.6% of pregnancies were reduced spontaneously
      after 9 weeks of gestation. The "take home" infant per delivery rates for the
      multifetal pregnancy reduction and expectant management groups were 87% and
      90.1%, respectively (P =.66). The mean gestational ages at delivery (+/-SE) for
      the multifetal pregnancy reduction and expectant management groups were 33.25 +/-
      1. 03 weeks and 32.04 +/- 0.58 weeks (P =.23), and the mean birth weights of
      infants delivered at >24 weeks of gestation were 2226 +/- 79 and 1796 +/- 44,
      respectively (P <.0001). There were no significant differences in perinatal
      mortality, gestational age at delivery, or "take home" infant per delivery rates
      between these groups. CONCLUSIONS: These data suggest that multifetal pregnancy
      reduction does not have a significant impact on the probability of live birth or
      on gestational age at delivery for women with triplets conceived with assisted
      reproductive technology.

PMID- 10942487
TI  - Lack of relationship between diurnal rhythms in fetal heart rate and maternal
      cortisol concentration.
AB  - In 9 pregnancies complicated by intrauterine growth restriction, 24-hour fetal
      heart rate recordings were made before and after betamethasone treatment to study
      the influence of cortisol on diurnal fetal heart rate rhythms. Maternal and fetal
      rhythms were correlated and did not change after betamethasone administration. We
      conclude that diurnal fetal heart rate rhythms are synchronized by the mother
      through a mechanism other than adrenal control.

PMID- 10942488
TI  - The clinical utility of fetal cell sorting to determine prenatally fetal E/e or
      e/e Rh genotype from peripheral maternal blood.
AB  - OBJECTIVE: This study was undertaken to determine the fetal E/e or e/e Rh
      genotype prenatally from peripheral maternal blood by examining sorted fetal
      cells from alloimmunized and nonalloimmunized pregnancies. STUDY DESIGN: Eighteen
      maternal peripheral venous blood samples were obtained before amniocentesis from
      15 pregnant women who were homozygous for the e allele. Five were not
      alloimmunized and 10 were alloimmunized. The mononuclear cell layer was isolated
      from the maternal blood and enriched for fetal nucleated red blood cells by flow
      cytometry with monoclonal antibodies to CD36 or CD71 and to glycophorin A. Eight
      samples were treated with CD45 monoclonal antibody-coated magnetic beads before
      they were sorted to deplete the maternal sample of leukocytes (CD45(+) cells). We
      defined the positive fetal cell fractions as the monoclonal antibody positive
      sorted cells derived from the maternal samples. These included sorted cells that
      were CD36(+)/glycophorin A(+), CD71(+)/glycophorin A(+) and CD45(-) cells that
      were sorted to become CD45(-)/CD36(+)/glycophorin A(+) or CD45(
      )/CD71(+)/glycophorin A(+). The negative fractions were the cells that were
      negative for either CD36/glycophorin A or CD71/glycophorin A or were the CD45(+)
      cells. Deoxyribonucleic acid was isolated from all fractions and amplified by
      polymerase chain reaction with allele-specific primers for the E or e Rh genes.
      Gel electrophoresis was performed to detect fetal E/e or e/e Rh genotype. The
      fetal E/e or e/e Rh genotype was confirmed by serologic and deoxyribonucleic acid
      testing. The accuracy of E/e or e/e Rh genotype determination from the positive
      cell fractions was compared with that of E/e or e/e Rh genotype determination
      from the negative fractions. RESULTS: Fetal E/e or e/e Rh genotype was determined
      correctly in 17 of 18 of the fetal cell enriched positive fractions (94%). Fetal
      E/e or e/e Rh genotype was determined correctly in 11 of 14 of the maternal
      samples in the negative unselected cell fractions (79%). Fetal E/e or e/e Rh
      genotype was determined correctly in 15 of 16 sample fractions that underwent
      magnetic bead separation with CD45 and were subsequently sorted into positive and
      negative fractions (94%). Fetal E/e or e/e Rh genotype was determined correctly
      in 13 of 13 of the samples obtained from the alloimmunized pregnancies (100%).
      CONCLUSIONS: The use of monoclonal antibodies for cell sorting or for magnetic
      separation predicted fetal E/e or e/e Rh genotype from peripheral maternal blood
      correctly in as many as 100% of alloimmunized pregnancies. Thus noninvasive fetal
      E/e or e/e Rh genotyping can be performed by polymerase chain reaction
      amplification of the rare fetal cells in maternal blood. The correct prediction
      of fetal E/e or e/e Rh genotype from the cell population not selected by the
      monoclonal antibodies suggests that there are fetal cell types other than fetal
      nucleated erythrocytes that can also be used as a source of fetal
      deoxyribonucleic acid for noninvasive genetic diagnosis. Improved technology may
      provide methods less laborious than cell sorting to accurately determine fetal Rh
      type from different fetal cell types that circulate in maternal blood.

PMID- 10942489
TI  - Vaginal fetal fibronectin measurements from 8 to 22 weeks' gestation and
      subsequent spontaneous preterm birth.
AB  - OBJECTIVE: We sought to determine the range of fetal fibronectin values in the
      vagina from 8 to 22 weeks' gestation, the factors associated with both low and
      high values, and whether high values are associated with gestational age at
      birth. STUDY DESIGN: Vaginal fetal fibronectin was quantitatively determined in a
      prospective cohort study of 13,360 women being evaluated for participation in the
      National Institute of Child Health and Human Development Maternal-Fetal Medicine
      Unit treatment trials for bacterial vaginosis and Trichomonas vaginalis. Fetal
      fibronectin values were correlated with gestational age at screening, race, the
      presence of bacterial vaginosis and Trichomonas vaginalis, and gestational age at
      delivery. RESULTS: Vaginal fetal fibronectin values at each gestational age
      ranged from unmeasurable to >1000 ng/mL, with median values always being <10
      ng/mL. Fetal fibronectin values declined progressively with increasing
      gestational age at sampling. Bacterial vaginosis and black race were associated
      with higher values, whereas nulliparity was associated with lower values. High
      values after 13 weeks' gestation were associated with a 2- to 3-fold increased
      risk of subsequent spontaneous preterm birth overall and a 4-fold increased risk
      of very early preterm birth. CONCLUSION: Elevated vaginal fetal fibronectin
      levels from 13 to 22 weeks' gestation are associated with a significantly
      increased risk of spontaneous preterm birth.

PMID- 10942490
TI  - Prenatal diagnosis of symptomatic congenital cytomegalovirus infection.
AB  - OBJECTIVE: The aim of this study was to evaluate whether the amniotic viral load
      of mothers with primary cytomegalovirus infection correlate with fetal or
      neonatal outcomes. STUDY DESIGN: Sixty-eight of 138 pregnant women with primary
      infection defined by immunoglobulin G seroconversion or the presence of
      immunoglobulin M with low immunoglobulin G avidity accepted amniocentesis.
      Polymerase chain reaction and quantitative polymerase chain reaction were used to
      detect amniotic fluid cytomegalovirus. Cytomegalovirus infection in neonates was
      determined by means of urinary viral isolation during the first week after birth
      or the histologic examination of tissue from aborted fetuses. RESULTS:
      Cytomegalovirus infection was found in 16 fetuses and neonates (23%), 5 of whom
      had symptoms. Quantitative polymerase chain reaction showed that the presence of
      >/=10(3) genome equivalents predicted mother-child infection with 100%
      probability; >/=10(5) genome equivalents predicted the development of a
      symptomatic infection. CONCLUSION: Fewer than expected cytomegalovirus-infected
      fetuses are at risk for development of cytomegaloviral disease, and this fact may
      be useful in counseling pregnant women with primary cytomegalovirus infection.

PMID- 10942491
TI  - Pemphigoid gestationis: a review.
AB  - Pemphigoid gestationis is a rare autoimmune vesiculobullous skin disease closely
      related to the pemphigoid group of blistering disorders. It is unique in that it
      is most frequently associated with pregnancy. Diagnosis is made on the basis of
      the presence of a subepidermal vesicle on routine histologic examination and of
      linear deposition of the third component of complement along the basement
      membrane zone of perilesional skin. Abnormal expression of major
      histocompatibility complex class II molecules in the placenta may trigger the
      initiating immunologic event in this organ, which is followed by cross-reactivity
      with an antigen present in the skin and the characteristic cutaneous signs of the
      disease. The immunogenetics of this disorder are interesting. A role for the
      involvement of major histocompatibility complex class II antigens seems likely
      because of the association with human leukocyte antigens DR3 and DR4. Major
      histocompatibility complex class III associations have also been observed, as has
      a high frequency of anti-human leukocyte antigen antibodies. We review the
      current understanding of the molecular biologic and immunogenetic properties of
      this disease and discuss treatment and potential impact on the fetus.

PMID- 10942492
TI  - Management of autonomic hyperreflexia with magnesium sulfate during labor in a
      woman with spinal cord injury.
AB  - Autonomic hyperreflexia, one of the gravest complications of delivery among women
      with spinal cord injury, has been treated with spinal or epidural anesthesia but
      not always successfully. We discovered dramatically beneficial effects of
      magnesium sulfate on autonomic hyperreflexia during labor in a patient with
      spinal cord injury at a high level.

PMID- 10942493
TI  - Vaginal subtotal hysterectomy and sacrospinous colpopexy: an option in the
      management of uterine prolapse.
AB  - Interest in vaginal hysterectomy is rising. Controversy remains regarding the
      value of conservation of the cervix at hysterectomy. Subtotal vaginal
      hysterectomy is a simple procedure that carries a low risk of morbidity. In
      combination with sacrospinous fixation it can be an option in the management of
      patients with marked uterine prolapse who desire retention of the cervix. The
      technique is described, and a case is reported.

PMID- 10942494
TI  - Successful application of extracorporeal membrane oxygenation and intra-aortic
      balloon counterpulsation as lifesaving therapy for a patient with amniotic fluid
      embolism.
AB  - A woman in labor was noted to have amniotic fluid embolism. Extracorporeal
      membrane oxygenation and intra-aortic balloon counterpulsation were performed
      post partum, and the vital signs became stable. The ensuing recovery was
      uneventful. We conclude that extracorporeal membrane oxygenation and intra-aortic
      balloon counterpulsation should be considered to save the life of a patient with
      amniotic fluid embolism and left ventricular failure unresponsive to medical
      therapy.

PMID- 10942495
TI  - Postoperative tailored radiotherapy for locally advanced breast carcinoma during
      pregnancy: a therapeutic dilemma.
AB  - A 45-year-old woman with breast carcinoma was found to be pregnant during
      postoperative radiotherapy. The pregnancy was desired. We performed in vivo and
      phantom radiation dosimetry. No effects on the embryo or treatment disadvantages
      for the patient were expected. Thirty-six months post partum the baby is healthy
      and the mother is free of disease.

PMID- 10942496
TI  - Primary amenorrhea caused by crushing trauma of the pelvis.
AB  - An 18-year-old woman sought treatment for primary amenorrhea. Crushing trauma of
      the pelvis in her childhood had caused separation between the uterine corpus and
      the cervix. Through a combined abdominal and vaginal approach the continuity of
      the uterine outflow tract was restored. Years later, after in vitro
      fertilization, the patient was delivered of a healthy term baby in an elective
      cesarean procedure.

PMID- 10942497
TI  - Pyoderma gangrenosum after cesarean delivery.
AB  - In this reported case of pyoderma gangrenosum after cesarean delivery, deep
      ulceration involved the entire lower abdomen before immunosuppressive treatment
      was started. Initial high doses of prednisolone followed by low doses of
      cyclosporine A led to complete resolution of the skin lesions. This case report
      illustrates the importance of early diagnosis and effective systemic
      immunosuppressive therapy of pyoderma gangrenosum.

PMID- 10942498
TI  - Isolated elevation of serum alkaline phosphatase level in an uncomplicated
      pregnancy: a case report.
AB  - Serum level of alkaline phosphatase of placental origin was increased >10-fold in
      a 28-year-old pregnant woman. Repeated abdominal ultrasonographic scans yielded
      negative results for hepatobiliary disease. After delivery of a healthy baby, the
      placenta showed no major pathologic characteristics, and the alkaline phosphatase
      level returned to the reference range.

PMID- 10942499
TI  - Exacerbation of endometriosis as a result of premenopausal tamoxifen exposure.
AB  - A 41-year-old woman with a history of endometriosis had breast carcinoma
      diagnosed and treated with tamoxifen. A pelvic mass was subsequently diagnosed
      and observed on serial ultrasonographic examinations to increase in size. At
      surgery extensive endometriosis was found. Exacerbation of endometriosis by
      tamoxifen may become more common as tamoxifen is used more frequently to reduce
      the risk of breast cancer among premenopausal women.

PMID- 10942500
TI  - Vulvar epithelial inclusion cyst as a late complication of childhood female
      traditional genital surgery.
AB  - Epithelial inclusion cysts may be a late complication of traditional female
      genital surgery. We present the case of a 19-year-old Eritrean woman who had been
      circumcised at birth and sought treatment for an enlarging vulvar mass that arose
      after the onset of puberty. Symptoms included pain, pruritus, and interference
      with walking.

PMID- 10942501
TI  - Cardiotoxic transplacental effect of idarubicin administered during the second
      trimester of pregnancy.
AB  - Polychemotherapy including idarubicin was administered during the second
      trimester to treat acute lymphoblastic leukemia. The infant delivered at 28
      weeks' gestation had acute cardiac failure attributed to the cardiotoxic effect
      of idarubicin. Cardiotoxicity may be caused by idarubicin's biophysical
      properties that facilitate its transplacental passage. Idarubicin should be used
      with extreme caution during pregnancy.

PMID- 10942502
TI  - Nifedipine as a safe and effective tocolytic agent in the treatment of preterm
      labor.

PMID- 10942504
TI  - Placental tissue and inhibition of uterine contraction by nitric oxide donors.

PMID- 10942506
TI  - Comments on sequential use of instruments at operative vaginal delivery.

PMID- 10942508
TI  - Vaginal breech deliveries.

PMID- 10942510
TI  - Hormone replacement therapy in breast cancer survivors.

PMID- 10942511
TI  - Treatment threshold probability for vaginitis.

PMID- 10942513
TI  - Clinical assessment of paravaginal defects.

PMID- 10942515
TI  - Retinoids and ovarian cancer.
AB  - Each year, an estimated 26,000 women in the United States are diagnosed with
      ovarian cancer. During any given year, approximately 14,500 women die from this
      disease. Ovarian cancer is the seventh most common cancer in women worldwide,
      after breast, cervix, colon/rectum, stomach, corpus uteri, and lung cancers. In
      the U.S., ovarian cancer is the second most common gynecologic cancer, and is the
      fourth leading cause of solid tumor cancer deaths among women. Currently,
      postoperative chemotherapy of ovarian cancer is still suboptimal. Drug resistance
      is a common problem resulting in only 20 approximately 30% overall 5-year
      survival rates. Clearly, continued development of alternative therapeutic
      strategies is essential for the management of this fatal disease. A number of
      recent studies have suggested that retinoids may play a potential role as an
      ovarian cancer chemotherapeutic agent. Retinoids, the natural and synthetic
      derivatives of vitamin A, have been shown to inhibit the growth of human ovarian
      cancer cells both in vivo and in culture. This review will initially summarize
      what is known about the pathological and molecular characteristics of ovarian
      carcinoma. It will then describe retinoid metabolism and the role of the cellular
      and nuclear retinoid binding proteins in mediating retinoid action. Following
      this general review of retinoids and their function, data supporting the role of
      retinoic acid as a suppresser of ovarian carcinoma cell growth will be presented.
      Particular attention will be paid to studies suggesting that members of the RB
      family of proteins and RB2/p130, in particular, are the molecular targets
      responsible for retinoid mediated inhibition of ovarian carcinoma cell growth.
      This review will then conclude with a brief discussion of two synthetic
      retinoids, 4 HPR R(fenretinide) and AHPN/CD437, which have been shown to induce
      apoptosis in ovarian tumor cells. It will be clear from the studies summarized in
      this review that retinoids represent a potentially powerful alternative to
      present chemotherapeutic approaches to the treatment of late stage ovarian
      cancer.

PMID- 10942516
TI  - Regulation of cell volume via microvillar ion channels.
AB  - A novel mechanism of cellular volume regulation is presented, which ensues from
      the recently introduced concept of transport and ion channel regulation via
      microvillar structures (Lange K, 1999, J Cell Physiol 180:19-35). According to
      this notion, the activity of ion channels and transporter proteins located on
      microvilli of differentiated cells is regulated by changes in the structural
      organization of the bundle of actin filaments in the microvillar shaft region.
      Cells with microvillar surfaces represent two-compartment systems consisting of
      the cytoplasm on the one side and the sum of the microvillar tip (or, entrance)
      compartments on the other side. The two compartments are separated by the
      microvillar actin filament bundle acting as diffusion barrier ions and other
      solutes. The specific organization of ion and water channels on the surface of
      microvillar cell types enables this two-compartment system to respond to hypo-
      and hyperosmotic conditions by activation of ionic fluxes along electrochemical
      gradients. Hypotonic exposure results in swelling of the cytoplasmic compartment
      accompanied by a corresponding reduction in the length of the microvillar
      diffusion barrier, allowing osmolyte efflux and regulatory volume decrease (RVD).
      Hypertonic conditions, which cause shortening of the diffusion barrier via
      swelling of the entrance compartment, allow osmolyte influx for regulatory volume
      increase (RVI). Swelling of either the cytoplasmic or the entrance compartment,
      by using membrane portions of the microvillar shafts for surface enlargement,
      activates ion fluxes between the cytoplasm and the entrance compartment by
      shortening of microvilli. The pool of available membrane lipids used for cell
      swelling, which is proportional to length and number of microvilli per cell,
      represents the sensor system that directly translates surface enlargements into
      activation of ion channels. Thus, the use of additional membrane components for
      osmotic swelling or other types of surface-expanding shape changes (such as the
      volume-invariant cell spreading or stretching) directly regulates influx and
      efflux activities of microvillar ion channels. The proposed mechanism of ion flux
      regulation also applies to the physiological main functions of epithelial cells
      and the auxiliary action of swelling-induced ATP release. Furthermore, the
      microvillar entrance compartment, as a finely dispersed ion-accessible peripheral
      space, represents a cellular sensor for environmental ionic/osmotic conditions
      able to detect concentration gradients with high lateral resolution. Volume
      regulation via microvillar surfaces is only one special aspect of the general
      property of mechanosensitivity of microvillar ionic pathways.

PMID- 10942517
TI  - AP-1 and C/EBP transcription factors contribute to mda-7 gene promoter activity
      during human melanoma differentiation.
AB  - Treatment of human melanoma cells with a combination of recombinant fibroblast
      interferon (IFN-beta) and the protein kinase C (PKC) activator mezerein (MEZ)
      causes a rapid and irreversible suppression in growth and terminal cell
      differentiation. Temporal subtraction hybridization combined with random clone
      selection, reverse Northern hybridization, high throughput microchip cDNA array
      screening, and serial cDNA library arrays permit the identification and cloning
      of genes that are differentially expressed during proliferative arrest and
      terminal differentiation in human melanoma cells. A specific melanoma
      differentiation associated (mda) gene, mda-7, exhibits reduced expression as a
      function of melanoma progression from melanocyte to metastatic melanoma. In
      contrast, treatment of metastatic melanoma cells with IFN-beta + MEZ results in
      expression of mda-7 mRNA and protein. To evaluate the mechanism underlying the
      differential expression of mda-7 as a function of melanoma progression and
      induction of growth arrest and differentiation in human melanoma cells the
      promoter region of this gene has been isolated from a human placental genomic
      library and characterized. Sequence analysis by GCG identifies multiple
      recognition sites for the AP-1 and C/EBP transcription factors. Employing a
      heterologous mda-7 luciferase gene reporter system, we demonstrate that ectopic
      expression of either AP-1/cJun or C/EBP can significantly enhance expression of
      the mda-7 promoter in melanoma cells. In contrast, a dominant negative mutant of
      cJun, TAM67, is devoid of promoter-enhancing ability. Western blot analyses
      reveals that cJun and the C/EBP family member C/EBP-beta are physiologically
      relevant transcription factors whose expression corresponds with mda-7 mRNA
      expression. Electrophoretic mobility shift assays (EMSA) performed using nuclear
      protein extracts from terminally differentiated human melanoma cells document
      binding to regions of the mda-7 promoter that correspond to consensus binding
      sites for AP-1 and C/EBP. These results provide further mechanistic insights into
      the regulation of the mda-7 gene during induction of terminal cell
      differentiation in human melanoma cells.

PMID- 10942518
TI  - EGF receptor residues leu(679), leu(680) mediate selective sorting of ligand
      receptor complexes in early endosomal compartments.
AB  - Dileucine-based motifs have been shown to regulate endosomal sorting of a number
      of membrane proteins. Previously, we have shown that the dileucine motif
      Leu(679), Leu(680) in the juxtamembrane domain of the human epidermal growth
      factor receptor is involved in the endosome-to-lysosome transport of ligand
      receptor complexes. Substitution of alanine residues for Leu(679), Leu(680) led
      to a reduction in ligand-induced receptor degradation without affecting
      internalization. In the current study, we have further characterized ligand
      dependent intracellular sorting of EGF receptors containing a L679A, L680A.
      Immunocytochemical studies reveal that although mutant receptors redistribute
      from the cell surface to transferrin receptor-positive endocytic vesicles similar
      to wild-type following ligand stimulation, their accumulation in Lamp-1-positive
      late endosomes/lysosomes is retarded compared to wild-type. Kinetic analysis of
      (125)I-EGF trafficking shows that reduced accumulation of internalized mutant
      receptors in Lamp-1-positive vesicles is due to rapid recycling of ligand
      receptor complexes from early endocytic compartments. In addition, the fraction
      of intracellular (125)I-EGF that is transported to late endocytic compartments in
      cells with mutant receptors is not as efficiently degraded as it is in cells with
      wild-type receptors. Furthermore, wild-type receptors in endocytic vesicles
      isolated by Percoll gradient fractionation are more resistant to in vitro
      digestion with proteinase K than mutant receptors. We propose that mutant
      receptors interact inefficiently with lysosomal sorting machinery, leading to
      their increased recycling. Our results are consistent with a model in which the
      Leu(679), Leu(680) signal facilitates sequestration of ligand-receptor complexes
      into internal vesicles of multivesicular endosome-to-lysosome transport
      intermediates.

PMID- 10942520
TI  - Is there a glycosaminoglycan-related heterogeneity of the thymic epithelium?
AB  - We determined the synthesis and secretion of glycosaminoglycans by three distinct
      preparations of mouse cultured thymic epithelial cells. These comprised primary
      cultures of thymic nurse cells (TNCs), which are normally located within the
      cortex of the thymic lobules, as well as two murine thymic epithelial cells,
      bearing a mixed, yet distinct, cortico-medullary phenotype. We first identified
      and measured the relative proportions of the various glycosaminoglycans in the
      three epithelial cells. Non-sulfated glycosaminoglycans are preponderantly
      secreted by the TNCs, while the sulfated glycans (particularly heparan sulfate)
      are relatively more abundant on the cell surface. The three types of epithelial
      cells differ markedly in their heparan sulfate composition, mainly due to
      different patterns of N- and O-sulfation. In addition, the cells differ in the
      synthesis and secretion of other glycosaminoglycans. Thus, TNCs secrete high
      amounts of dermatan sulfate + chondroitin sulfate to the culture medium. IT-76M1
      cells secrete high proportions of heparan sulfate while 2BH4 cells show a more
      equilibrated proportion of dermatan sulfate/chondroitin sulfate and heparan
      sulfate. The three epithelial cells also differ in their capacity to produce
      hyaluronic acid and 2BH4 cells are distinguished by their high rate of synthesis
      of this glycosaminoglycan. In conclusion, our results show that distinct thymic
      epithelial cells can synthesize different types of glycosaminoglycans. Although
      it remains to be definitely determined whether these differences reflect the in
      vivo situation, our data provide new clues for further understanding of how
      glycosaminoglycan-mediated interactions behave in the thymus.

PMID- 10942519
TI  - Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by
      retinoic acid receptors.
AB  - Retinoids have great promise in the area of cancer therapy and chemoprevention.
      These natural and synthetic derivatives of vitamin A have been shown to play an
      important role in regulating cell differentiation and proliferation. While all
      trans-retinoic acid (ATRA) has been demonstrated to inhibit the growth of several
      ovarian tumor cell lines, other ovarian carcinoma cell lines have been found to
      be resistant to retinoid dependent growth suppression. Interestingly, a novel
      synthetic retinoid, CD437 or AHPN, has been demonstrated to inhibit the growth of
      both ATRA-sensitive (CA-OV3) and ATRA-resistant (SK-OV3) ovarian tumor cell lines
      as well as to induce apoptosis. The overall goal of this research was to
      understand the mechanism by which AHPN/CD437 induces apoptosis in ovarian tumor
      cell lines. Since a number of studies have demonstrated the importance of nuclear
      receptors (RARs and RXRs) in mediating cellular responses to retinoids, we wished
      to determine the role of RARs in mediating the AHPN/CD437 response. We modulated
      RAR level and function by overexpressing either wild type RAR-gamma or a pan
      dominant negative mutant of all RAR subtypes called RAR-beta (R269Q), or through
      the use of an RAR-gamma antagonist, MM11253. We found that inhibition of RAR
      function reduced but did not eliminate induction of apoptosis in both CA-OV3 and
      SK-OV3 cells by AHPN/CD437. Likewise, overexpression of wild type RAR-gamma was
      found to increase apoptosis after treatment with AHPN/CD437. Our results suggest
      that in ovarian carcinomas, AHPN/CD437 induced apoptosis is mediated at least in
      part via an RAR pathway.

PMID- 10942521
TI  - Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene
      expression in oxidatively-challenged astroglia.
AB  - Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that reduces
      superoxide anion to hydrogen peroxide in cell mitochondria. MnSOD is
      overexpressed in normal aging brain and in various central nervous system
      disorders; however, the mechanisms mediating the upregulation of MnSOD under
      these conditions remain poorly understood. We previously reported that cysteamine
      (CSH) and other pro-oxidants rapidly induce the heme oxygenase-1 (HO-1) gene in
      cultured rat astroglia followed by late upregulation of MnSOD in these cells. In
      the present study, we demonstrate that antecedent upregulation of HO-1 is
      necessary and sufficient for subsequent induction of the MnSOD gene in neonatal
      rat astroglia challenged with CSH or dopamine, and in astroglial cultures
      transiently transfected with full-length human HO-1 cDNA. Treatment with potent
      antioxidants attenuates MnSOD expression in HO-1-transfected astroglia, strongly
      suggesting that intracellular oxidative stress signals MnSOD gene induction in
      these cells. Activation of this HO-1-MnSOD axis may play an important role in the
      pathogenesis of Alzheimer disease, Parkinson disease and other free radical
      related neurodegenerative disorders. In these conditions, compensatory
      upregulation of MnSOD may protect mitochondria from oxidative damage accruing
      from heme-derived free iron and carbon monoxide liberated by the activity of HO
      1.

PMID- 10942523
TI  - Isolation, characterization, and chondrogenic potential of human bone marrow
      derived multipotential stromal cells.
AB  - Multipotential bone marrow stromal cells have the ability to differentiate along
      multiple connective tissue lineages including cartilage. In this study, we
      developed an efficient and reproducible procedure for the isolation of stromal
      cells from bone marrow aspirates of normal human donors based on the expression
      of endoglin, a type III receptor of the transforming growth factor-beta (TGF
      beta) receptor family. We demonstrate that these cells have the ability of
      multiple lineage differentiation. Stromal cells represented 2-3% of the total
      mononuclear cells of the marrow. The cells displayed a fibroblastic colony
      formation in monolayer culture and maintained similar morphology with passage.
      Expression of cell surface molecules by flow cytometry displayed a stable
      phenotype with culture expansion. When cocultured with hematopoietic CD34(+)
      progenitor cells, stromal cells were able to maintain their ability to support
      hematopoiesis in vitro. Culture expanded stromal cells were placed in a 3
      dimensional matrix of alginate beads and cultured in serum-free media in the
      presence of TGFbeta-3 for chondrogenic lineage progression. Increased expression
      of type II collagen messenger RNA was observed in the TGFbeta3 treated cultures.
      Immunohistochemistry performed on sections of alginate beads detected the
      presence of type II collagen protein. This isolation procedure for stromal cells
      and the establishment of the alginate culture system for chondrogenic progression
      will contribute to the understanding of chondrogenesis and cartilage repair.

PMID- 10942522
TI  - Osteogenic protein-1 differentially regulates the mRNA expression of bone
      morphogenetic proteins and their receptors in primary cultures of osteoblasts.
AB  - The mRNA expression patterns of several bone morphogenetic proteins (BMPs) and
      their receptors (BMPRs) in long-term primary cultures of fetal rat calvaria (FRC)
      cells were examined by Northern analysis. Their temporal orders of expression
      were correlated with those of several biochemical markers characteristic of
      osteoblastic cell differentiation. Distinct temporal patterns of expression of
      BMPs and BMPRs during osteoblastic cell differentiation were observed. BMP-2 and
      BMP-7 mRNA levels did not change significantly. BMP-4 mRNA expression increased
      and reached a peak prior to matrix formation. BMP-5 mRNA expression increased
      during the mineralization phase and BMP-6 mRNA expression increased throughout
      all phases of cell differentiation. Effects of BMP-7 (Osteogenic Protein-1; OP-1)
      on the expression patterns of several other members of the BMP family and the
      receptors were also studied. OP-1 downregulated the BMP-4, -5, and -6 mRNA levels
      by a maximal of 2-fold, 1.5-fold, and 6-fold, respectively. OP-1 did not change
      significantly the OP-1 and BMP-2 mRNA expression. Of the three type I BMPR
      examined, OP-1 upregulated ActR-I and BMPR-IA mRNA expression slightly but with
      statistical significance. OP-1 downregulated BMPR-IB mRNA expression slightly. OP
      1 upregulated BMPR-II mRNA expression by a maximum of 2-fold. Our findings
      demonstrate that OP-1 differentially regulates the mRNA expression of several
      related members of the BMP family and their receptors in osteoblasts. The
      observations suggest that OP-1 action on osteoblastic cells involves a complex
      regulation of gene expression of related members of the BMP family and their
      receptors in a cell differentiation stage dependent manner.

PMID- 10942524
TI  - Perturbation of EGF-activated MEK1 and PKB signal pathways by TGF-beta1
      correlates with perturbation of EGF-induced cyclin D1 and DNA synthesis by TGF
      beta1 in C3H 10T1/2 cells.
AB  - In mouse C3H 10T1/2 cells, we previously reported that TGF-beta1 first delays and
      later potentiates EGF-induced DNA synthesis corresponding to an inhibition of EGF
      induced cyclin D1 expression at t = 13 h. We report here that in accord with DNA
      synthesis kinetics, TGF-beta1 initially suppresses EGF-induced cyclin D1
      expression then later releases the inhibition. Furthermore, TGF-beta1 also first
      decreases and later potentiates the levels of EGF-activated MEK1/MAPK and PKB,
      indicating the existence of cross talk between TGF-beta 1- and EGF-activated
      signal transduction pathways. PD98059, the specific inhibitor of MEK1,
      significantly blocks EGF-induced DNA synthesis, whereas wortmannin, the PI3K
      inhibitor, exerts a modest inhibitory effect, which suggests that the activation
      of MEK1-MAPK pathway plays a major role in EGF-induced DNA synthesis and the
      activation of PI3K-PKB pathway plays a minor role. Upon examination of mechanisms
      underlying the cross talk, it was discovered that application of TGF-beta1
      triggers a rapid association between Raf-1 and catalytic subunits of PKA, which
      are reported to be able to inactivate Raf-1 upon activation. Therefore, TGF-beta1
      may activate PKA to inhibit the EGF-activated MEK1-MAPK pathway. The wortmannin
      sensitive phosphorylation at the thr(389) site is necessary for activation of
      p70s6K, an important kinase involved in mitogen-stimulated protein synthesis.
      Although we found that EGF-stimulated p70s6K phosphorylates through a MAPK
      dependent and a MAPK-independent (wortmannin-sensitive) pathway, TGF-beta1 failed
      to block EGF-triggered phosphorylation of p70s6K at thr(389) and
      thr(421)/ser(424) sites, implying that PKB inhibition by TGF-beta1 may result
      from inhibition of PDK1 activity instead of inhibition of PI3K activity. These
      data also suggest that TGF-beta1 may selectively perturb certain EGF-activated
      MAPK pools.

PMID- 10942525
TI  - Endotoxin increases intercellular resistance in microvascular endothelial cells
      by a tyrosine kinase pathway.
AB  - Gap junction communication between microvascular endothelial cells has been
      proposed to contribute to the coordination of microvascular function. Septic
      shock may attenuate microvascular cell-to-cell communication. We hypothesized
      that lipopolysaccharide (LPS) attenuates communication between microvascular
      endothelial cells derived from rat hindlimb skeletal muscle. Endothelial cells
      grown in monolayers expressed mRNA for connexin 37, 40, and 43. The expression of
      connexin 43 protein was confirmed, but connexin 40 protein was not detected by
      immunocytochemistry or immunoblot analysis. Intercellular resistance between
      cells of the monolayer, calculated using a Bessel function model, was increased
      from 3.3 to 5.3 MOmega by LPS. The effect was seen after 1 h of exposure and
      required a minimum concentration of 10 ng/ml. Intercellular resistance returned
      to normal 1 h following removal of LPS. Neither the response to LPS, nor its
      reversal, was blocked by the protein synthesis inhibitor cycloheximide (10
      microg/ml). Pretreatment of monolayers with the tyrosine kinase inhibitors PP-2
      (10 nM), lavendustin-C (1 microM), and geldanamycin (200 nM) prevented this LPS
      response; geldanamycin was also able to reverse the response. Inhibitors of MAP
      kinases, PD 98059 (5 microM) and SB 202190 (5 microM), and PKC (500 nM
      bisindolylmaleimide I) were unable to block the LPS response. We propose that LPS
      attenuates cell-to-cell communication through a signaling pathway that is
      tyrosine kinase dependent.

PMID- 10942526
TI  - Interleukin-2 induces cell cycle perturbations leading to cell growth inhibition
      and death in malignant mesothelioma cells in vitro.
AB  - Previous report indicated that Interleukin-2 (IL-2) is able to inhibit the growth
      of IL-2-receptor-positive cancer cell lines without any involvement of the immune
      system, through IL-2-induced alterations of the cell cycle kinetics. In this
      study we provide evidence that IL-2 exerts anti-proliferative effect on three
      human malignant mesothelioma (MMe) cells in vitro, while no effects were observed
      on normal human mesothelial cell (HMC) primary cultures. The growth inhibitory
      effect of IL-2 on neoplastic cells appeared to depend on the baseline
      proliferative status of these cells. Indeed, in highly proliferating MMe cells,
      we observed a reduction of malignant cells in the S-phase of the cell cycle, with
      an accumulation in G0/G1, followed by apotosis for longer incubations or exposure
      to higher doses. On the contrary, in MMe cells proliferating at lower rate, IL-2
      induces only a late cytotoxic effect, leading to apoptosis, without significantly
      affecting the cell cycle. IL-2Rbeta mRNA was detectable by RT-PCR in all MMe
      cells, IL-2Ralpha mRNA in one only out the three assayed and IL-2Rgamma mRNA in
      none. In addition, mRNA specific for the IL-2Rbeta-associated Jak-1 tyrosine
      kinase was expressed in all MMe cell lines, further suggesting that IL-2Rbeta may
      play a role in the observed effects. Very low, albeit detectable, levels of IL
      2Rbeta chain appeared to be expressed at the cell surface of MMe cells by
      indirect immunofluorescence and FACS analyses. Finally, Ca(++) fluxes were
      rapidly induced when MMe cells were exposed to exogenous IL-2.

PMID- 10942527
TI  - Cell injury unmasks a latent proangiogenic phenotype in mice with increased
      expression of FGF2 in the retina.
AB  - Fibroblast growth factor-2 (FGF2) is a potent mitogen for vascular endothelial
      cells and exogenous administration of FGF2 stimulates angiogenesis. However,
      increased expression of FGF2 in the retina does not cause angiogenesis. One
      possible explanation is that FGF2 may not be capable of initiating angiogenesis
      unless it is administered in pharmacologic levels or there is coexpression of
      another angiogenic factor. Alternatively, there may be control mechanisms that
      sequester FGF2 in vivo, preventing it from manifesting its in vitro angiogenic
      activity. We tested the first hypothesis by crossing mice that express FGF2 in
      the retina with mice that express vascular endothelial growth factor (VEGF) in
      the retina. Surprisingly, despite comparable levels of VEGF expression, mice that
      expressed both FGF2 and VEGF had significantly less neovascularization than mice
      that expressed VEGF alone. The second hypothesis was tested by treating Rho/FGF2
      transgenic mice with low-intensity laser photocoagulation that disrupts
      photoreceptors, but does not rupture Bruch's membrane, or intense laser that
      ruptures Bruch's membrane. In Rho/FGF2 transgenics, but not wild type mice,
      choroidal neovascularization developed in areas of low-intensity laser. Both wild
      type and transgenic mice developed choroidal neovascularization in areas of
      intense laser that ruptured Bruch's membrane, but the area of neovascularization
      was significantly greater in transgenics. These data suggest that increased
      retinal expression of FGF2 is angiogenic only when it is accompanied by cell
      injury that overcomes sequestration control mechanisms.

PMID- 10942528
TI  - Increased expression of IGF-binding protein-5 in Duchenne muscular dystrophy
      (DMD) fibroblasts correlates with the fibroblast-induced downregulation of DMD
      myoblast growth: an in vitro analysis.
AB  - In DMD the progressive loss of muscle ability and concomitant increasing fibrosis
      might originate from, besides other causes, the fibroblast paracrine inhibition
      of satellite cell "growth." In this study we report that in myoblast/fibroblast
      coculture experiments, the presence of DMD fibroblasts negatively interfered with
      DMD myoblast growth to an extent directly proportional to the percentage of DMD
      fibroblasts present in the mixed-cell cultures. Moreover, the observation that
      media conditioned with proliferating DMD fibroblasts inhibited the growth of DMD
      myoblasts more seriously than did control fibroblast-conditioned media suggested
      a paracrine effect by diffusible factors. IGF-binding proteins could act as such
      diffusible factors; in fact, IGFBP-5 transcript increased threefold in DMD
      fibroblasts proliferating in DMD muscle extracts, whereas IGFBP-3 mRNA decreased.
      In addition, high levels of IGFBP-5 protein were detected in DMD fibroblast
      conditioned media. In neutralizing IGFBP-5 in DMD fibroblast-conditioned media by
      means of specific antibodies, or inhibiting IGFBP-5 gene expression in DMD
      fibroblasts by means of oligo antisense, the fibroblast-conditioned media lost
      inhibitory power over DMD myoblast proliferation.

PMID- 10942529
TI  - Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in
      human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell
      cycle regulators and induction of G1 arrest and apoptosis.
AB  - There is an increasing interest in identifying potent cancer preventive and
      therapeutic agents against prostate cancer (PCA). In a recent study, we showed
      that a polyphenolic fraction isolated from grape seeds (hereafter referred to as
      GSP) that is substantially rich in antioxidant procyanidins exerts exceptionally
      high preventive effects against tumorigenesis in a murine skin model. In the
      present study, we investigated the anticarcinogenic effect of GSP against PCA by
      employing DU145 human prostate carcinoma cells. GSP treatment (10-100 microg/mL
      doses for 2-6 d) of cells resulted in a highly significant (P < 0.01-0.001)
      inhibition of cell growth in both dose- and time-dependent manner. Compared with
      the vehicle, 2 d of GSP treatment resulted in 27, 39, and 76% growth inhibition
      at 50, 75, and 100 microg/mL doses, respectively, whereas 28-97% and 12-98%
      inhibition was evident at 10-100 microg/mL doses of GSP after 4 and 6 d of
      treatment, respectively. These doses of GSP also resulted in dose- and time
      dependent cell death (6-50%, P <0.1-0. 001) that was later characterized as
      apoptotic death. In molecular mechanistic studies, treatment of DU145 cells with
      GSP at 25-75 microg/mL doses for 24, 48, and 72 h resulted in 77-88%, 65-93%, and
      38-98% reduction, respectively (P < 0.001), in phospho-extracellular signal
      regulated protein kinase (ERK) 1 and 78%, 19-76%, and 63-71% reduction (P < 0.1
      0.001) in phospho-ERK2 levels, respectively. In other studies, similar doses of
      GSP showed up to 1.9-fold increases in Cip1/p21 and a significant (P < 0.001)
      decrease in cyclin-dependent kinase (CDK) 4 (up to 90% decrease), CDK2 (up to 50%
      decrease), and cyclin E (up to 60% decrease). GSP treatment of DU145 cells also
      resulted in a significant (P < 0.001) G1 arrest in cell-cycle progression in a
      dose-dependent manner. The growth-inhibitory and cell-death effects of GSP were
      also observed in another human PCA line, LNCaP. Together, these results suggest
      that GSP may exert strong anticarcinogenic effect against PCA and that this
      effect possibly involves modulation of mitogenic signaling and cell-cycle
      regulators and induction of G1 arrest, cell-growth inhibition, and apoptotic
      death. Mol. Carcinog. 28:129-138, 2000.

PMID- 10942530
TI  - Differential expression of p16(INK4a) in azoxymethane-induced mouse colon
      tumorigenesis.
AB  - Alterations in the p16(INK4a) gene have been implicated in the pathogenesis of
      different human cancers and animal tumors. We postulated that alterations in the
      p16(INK4a) gene may also be involved in mouse colon tumorigenesis induced by the
      chemical carcinogen azoxymethane (AOM). In the present study, p16(INK4a) deletion
      status and its expression were examined in an AOM-induced mouse colon tumor
      model. Polymerase chain reaction-based deletion analysis of p16(INK4a) exon 2
      showed no deletions in the colon tumors. The expression and localization of
      p16(INK4a) and its gene product were examined by reverse transcription-polymerase
      chain reaction and immunohistochemical analyses, respectively. The p16(INK4a)
      mRNA levels were low, and in some cases undetectable, in control colon tissue.
      However, colon tumors exhibited an eightfold increase in p16(INK4a) mRNA level
      when compared with control colon tissue (P < 0.01). Whereas control colon
      epithelium was uniformly negative for p16(INK4a) immunoreactivity, p16(INK4a)
      immunoreactive cells were markedly increased in preneoplastic lesions and
      adenomas isolated from AOM-treated mice. To further examine the p16(INK4a)
      regulatory pathway, the retinoblastoma tumor-suppressor protein (Rb) was also
      examined immunohistochemically in these tissues. A heterogeneous Rb
      immunostaining was observed in preneoplastic lesions and adenomas.
      Immunohistochemical analysis also showed a reciprocal relationship between
      p16(INK4a) and Rb protein expression. These findings suggest that alterations in
      the p16(INK4a)/Rb pathway may play an important role in AOM-induced mouse colon
      tumorigenesis. Mol. Carcinog. 28:139-147, 2000.

PMID- 10942531
TI  - Inhibition of ultraviolet B-induced AP-1 activation by theaflavins from black
      tea.
AB  - Theaflavins are believed to be key active components in black tea for
      chemoprevention of cancer. However, the molecular mechanisms underlying the
      inhibitory effects of theaflavins are not clear. With the JB6 mouse epidermal
      cell line, we investigated the effects of theaflavins on ultraviolet (UV) B
      radiation-induced activator protein-1 (AP-1)-dependent transcriptional activation
      and compared them with (-)-epigallocatechin-3-gallate (EGCG), a major green tea
      polyphenol that has cancer chemopreventative activity. Theaflavins and EGCG
      inhibited UVB-induced AP-1 activation in a concentration-dependent manner. The
      inhibitory effects of theaflavins were stronger than those of EGCG. We found that
      theaflavins significantly inhibited activation of extracellular signal-regulated
      protein kinases and c-jun NH(2)-terminal kinases. Because the transcription
      factor AP-1 is important in the process of tumor promotion, the inhibitory effect
      of these polyphenols on AP-1 activation may further explain the anti-tumor
      promotion action of these tea constituents. Mol. Carcinog. 28:148-155, 2000.

PMID- 10942532
TI  - Ki-ras and the characteristics of mouse lung tumors.
AB  - Codon 12 mutations are frequent in the Ki-ras oncogene in human lung
      adenocarcinomas, but the effects of these alterations have not been well
      characterized in lung epithelial cells. Murine primary lung tumors derived from
      peripheral epithelial cells also may present Ki-ras mutations and are useful
      models for study of early phases of tumor development. One hypothesis is that Ki
      ras mutation and/or a Ki-ras p21 increase could enhance Ki-ras p21-GTP and cell
      cycle stimulation through raf-1 and extracellularly regulated protein kinases
      (Erks). We examined lung tumors 1-7 mm in largest dimension initiated in male
      Swiss mice by N-nitrosodimethylamine for pathologic type, Ki-ras mutations and
      levels of total Ki-ras p21, Ki-ras p21 bound to GTP, raf-1, Erk1 and Erk2 and
      their phosphorylated (activated) forms, and proliferating cell nuclear antigen.
      Total Ki-ras p21 and activated ras-GTP were not significantly greater in tumors
      than in normal lung or in tumors with versus those without Ki-ras mutations.
      Carcinomas with Ki-ras mutations were significantly smaller than those without
      mutations. Carcinomas were significantly larger than adenomas only for tumors
      without mutations. High levels of Erk2 and correlation of Erk2 amount with ras
      GTP were specific characteristics of tumors with Ki-ras mutations. Size of all
      tumors correlated with ras-GTP but not with proliferating cell nuclear antigen.
      Raf-1 was expressed mainly in alveolar macrophages in normal lung but was focally
      upregulated in papillary areas of some tumors. The results indicate that Ki-ras
      influences the characteristics of lung tumors, but a linear ras-raf-Erk-cell
      cycle control sequence does not adequately characterize tumorigenic events in
      this model. Mol. Carcinog. 28:156-167, 2000.

PMID- 10942533
TI  - Promotion of hepatocarcinogenesis by phenobarbital in c-myc/TGF-alpha transgenic
      mice.
AB  - Previous work has shown that phenobarbital (PB) can promote cell survival in
      double transgenic c-myc/transforming growth factor (TGF)-alpha mice. This was
      achieved through a suppression of cell death brought about, at least in part, by
      a general increase in the level of bcl-2 protein and a decrease in TGF-beta1 in
      treated versus untreated animals. No changes were found in TGF-beta type II
      receptor or in bcl-X(L) protein levels. In the present work, we followed these
      animals for up to 31 wk of age (28 wk of treatment), by which time numerous
      tumors could be observed. A PB-dependent decrease in tumor latency and a
      significant increase in multiplicity were seen. No statistically significant
      changes in the phenotype of foci, nodules, or neoplasms were observed after PB
      administration, and no effect on median tumor size was detected. Levels of the
      anti-apoptotic protein bcl-2 did not correlate with tumor formation in PB-treated
      animals. However, in untreated mice, bcl-2 was higher in tumors than in
      surrounding tissue in all tumors examined. We believe that the PB-dependent
      modification of tumorigenesis in the livers of c-myc/TGF-alpha mice was
      predominantly a result of the ability of this drug to block cell death during the
      early stages of tumor development. The effect of PB was exerted apparently by a
      pathway similar to, but separate from, that of TGF-alpha. However, these pathways
      appear to converge downstream, having common effectors in the form of bcl-2
      family proteins. Mol. Carcinog. 28:168-173, 2000.

PMID- 10942536
TI  - Viscosity of Nonionic Polymer/Anionic Surfactant Complexes in Water.
AB  - The polymer-micelle model, formerly established by Cabane, is revised to develop
      a new viscosity equation to describe the dependence of dilute solution viscosity
      on polymer concentration in PEG/SDS aqueous solutions. Two parameters inthe new
      equation were proposed to characterize the influence of the polymer solution
      viscosity on the added surfactant. The viscosity data of polyethylene glycol
      (PEG) solutions containing sodium dodecyl sulfate (SDS) were measured by the
      Ubbelohde dilution viscometer and the new equation proved to be in good agreement
      with the experimental data. Copyright 2000 Academic Press.

PMID- 10942534
TI  - BRCA2-null embryonic survival is prolonged on the BALB/c genetic background.
AB  - Women who inherit mutations in the BRCA2 cancer susceptibility gene have an 85%
      chance of developing breast cancer. The function of the BRCA2 gene remains
      elusive, but there is evidence to support its role in transcriptional
      transactivation, tumor suppression, and the maintenance of genomic integrity.
      Individuals with identical BRCA2 mutations display a different distribution of
      cancers, suggesting that there are low-penetrance genes that can modify disease
      outcome. We hypothesized that genetic background could influence embryonic
      survival of a Brca2 mutation in mice. Brca2-null embryos with a 129/SvEv genetic
      background (129(B2-/-)) died before embryonic day 8. 5. Transfer of this Brca2
      mutation onto the BALB/cJ genetic background (BALB/c(B2-/-)) extended survival to
      embryonic day 10.5. These results indicate that the BALB/c background harbors
      genetic modifiers that can prolong Brca2-null embryonic survival. The extended
      survival of BALB/c(B2-/-) embryos enabled us to ask whether transcriptional
      regulation of the Brca1 and Brca2 genes is interdependent. The interdependence of
      Brca1 and Brca2 was evaluated by studying Brca2 gene expression in BALB/c(B1-/-)
      embryos and Brca1 gene expression in BALB/c(B2-/-) embryos. Nonisotopic in situ
      hybridization demonstrated that Brca2 transcript levels were comparable in
      BALB/c(B1-/-) embryos and wild-type littermates. Likewise, reverse transcriptase
      polymerase chain reactions confirmed Brca1 mRNA expression in embryonic day 8.5
      BALB/c(B2-/-) embryos that was comparable to Brca2-heterozygous littermates.
      Thus, the Brca1 and Brca2 transcripts are expressed independently of one another
      in Brca1- and Brca2-null embryos. Mol. Carcinog. 28:174-183, 2000.

PMID- 10942537
TI  - Three-Dimensional Arrays Formed by Monodisperse TiO(2) Coated on SiO(2) Spheres.
AB  - Uniform coatings of TiO(2) on monodisperse spheres of silica have been obtained.
      The resulting particle sizes are within the range 0.4 to 1 um. The thickness of
      the coating can be controlled by adjusting nuclei sizes (silica sphere), reaction
      times, and water and surfactant concentrations. The TiO(2)/SiO(2) spheres were
      sedimented to achieve structures with three-dimensional order. Three-dimensional
      ordered materials with higher refractive index were obtained by transforming the
      amorphous titania layer to rutile by thermal treatment with improved mechanical
      rigidity. The sphere composition, quality, and morphology have been assessed by
      different techniques. Copyright 2000 Academic Press.

PMID- 10942535
TI  - Distinct expression of CDX2 and GATA4/5, development-related genes, in human
      gastric cancer cell lines.
AB  - CDX2 is a tumor-suppressor homeobox gene involved in colon carcinogenesis, but
      its role in gastric cancer is unknown. Although GATA4, -5 and, -6 transcription
      factors have distinct functions in the regulation of gastrointestinal epithelial
      cell differentiation, there have been no reports regarding GATA4/5/6 alterations
      in gastrointestinal carcinomas. By using a semiquantitative reverse transcription
      polymerase chain reaction assay, we studied the expression of gut development
      related genes CDX2/1 and GATA4/5/6 in 11 human gastric cancer cell lines. The
      expression of CDX2 appeared to progressively decrease with the transition from
      well differentiated to poorly differentiated cancer cell lines. CDX1 was below
      detectable levels in all cell lines. The expression of GATA4 and GATA5 was
      undetectable in four and six cell lines, respectively, whereas the majority of
      the cell lines expressed GATA6 abundantly. These results suggest that CDX2 and
      GATA4/5 may be associated with the carcinogenesis of the stomach. Mol. Carcinog.
      28:184-188, 2000.

PMID- 10942538
TI  - Study of the Adsorption of Glutathione on a Gold Electrode by Using
      Electrochemical Quartz Crystal Impedance, Electrochemical Impedance Spectroscopy,
      and Cyclic Voltammetry.
AB  - Adsorption of a biological peptide, glutathione, on a gold electrode was studied
      by using electrochemical quartz crystal impedance (EQCI), electrochemical
      impedance spectroscopy (EIS), and cyclic voltammetry (CV) techniques. The time
      courses of responses of piezoelectric and electrochemical impedance parameters
      were simultaneously obtained during the adsorption processes of the two forms of
      peptide, oxidized and reduced glutathione. It was found that the frequency curve
      due to the oxidized glutathione (GSSG) adsorption exhibited a character of a sum
      of two exponential functions. For reduced glutathione (GSH), the frequency
      adsorption curve could be expressed by a first-order reaction kinetic model and
      the corresponding kinetic parameters at different amounts of GSH were obtained.
      The heterogeneous charge-transfer rate constants of ferricyanide/ferrocyanide
      before and after the peptide adsorption were determined by CV and EIS methods,
      respectively. According to the simple equivalent electric network of the
      electrochemical interface, the electrochemical impedance parameters were also
      obtained. The results showed that the proposed method should be found in wider
      applications in interfacial biochemistry studies since these combined techniques
      have advantages in real time multidimensional information including
      electrochemical and electrochemical impedance parameters. Copyright 2000 Academic
      Press.

PMID- 10942539
TI  - Incompatibility and Phase Separation in a Bovine Serum Albumin/beta-Casein/Water
      Ternary Film at the Air-Water Interface.
AB  - Thermodynamic incompatibility and two-dimensional phase separation in a bovine
      serum albumin (BSA)/beta-casein/water ternary film at the air-water interface has
      been studied using an epifluorescence microscopy technique. The incompatibility
      between BSA and beta-casein at the air-water interface was deduced from deviation
      of the experimental equilibrium composition of the proteins in the mixed
      saturated monolayer film from that predicted by the Langmuir-type competitive
      adsorption model at various bulk concentration ratios. Fluorescence microscopy of
      the mixed monolayer film showed distinct phase-separated BSA-rich and beta-casein
      rich regions coexisting with inhomogeneous mixed regions. BSA always tended to be
      the dispersed phase and beta-casein the continuous phase. It is suggested that
      because the free energy at the "interfaces" between the phase-separated regions
      is generally higher than at other regions of the film, they may act as zones of
      instability in protein-stabilized foams and possibly emulsions. Copyright 2000
      Academic Press.

PMID- 10942540
TI  - Stability of Streaming in an Electrified Maxwell Fluid Sheet Influenced by a
      Vertical Periodic Field in the Absence of Surface Charges.
AB  - The problem of electroviscoelastic Kelvin-Helmholtz waves of Maxwellian fluids
      under the influence of a vertical periodic electric field is studied in the
      absence of surface charges. The system is composed of a streaming dielectric
      fluid sheet of finite thickness embedded between two different streaming semi
      infinite dielectric fluids. Due to the streaming flow and the influence of a
      periodic force, a mathematical simplification is considered. The weak
      viscoelastic effects are taken into account so that their contributions are
      demonstrated in the boundary conditions. The approximate equations of motion are
      solved in the absence of viscoelastic effects. The solutions of the linearized
      equations of motion and boundary conditions lead to two simultaneous Mathieu
      equations of damping terms having complex coefficients. Symmetric or
      antisymmetric deformation that relaxes the coupled Mathieu equations and yields a
      single Mathieu equation is considered. Stability criteria are discussed and
      numerical estimation shows that the increase in the sheet thickness plays a
      destabilizing effect in the presence or in the absence of the field frequency as
      well as the field intensity. In the absence of the field frequency the velocity
      ratio between the upper fluid velocity and the sheet velocity has a destabilizing
      influence, while that between the velocity of the lower fluid and the velocity of
      the sheet has a stabilizing influence. Moreover, the viscosity ratios have a
      damping influence while the elasticity ratios have a destabilizing influence.
      Furthermore, a range of general deformations of the surface deflections is
      studied. Moreover, the stability behavior for the resonance cases is studied and
      discussed. The coupled Mathieu equations are analyzed by the multiple scale
      method. The numerical examination for stability yields some changes in the
      stability behavior. The fluid sheet thickness plays a stabilizing role in the
      presence of a constant field while the damping role is observed for the resonance
      case. Similar results are found for both the stratified velocities and the
      stratified relaxation times. The dual role of the stratified viscosities is
      observed in the presence or the absence of the field frequency. Copyright 2000
      Academic Press.

PMID- 10942541
TI  - Diffusion Coefficients of Three Organic Solutes in Aqueous Sodium Dodecyl Sulfate
      Solutions.
AB  - Tracer diffusion coefficients of phenol, toluene, and benzoic acid in aqueous
      solutions of sodium dodecyl sulfate (SDS) were measured by the Taylor dispersion
      technique. In addition, the viscosities and densities of the SDS solutions were
      measured. For phenol and toluene, the effect of micelle formation on the
      diffusion coefficient is pronounced. When the SDS concentration is below the
      critical micelle concentration (cmc), the diffusion coefficients are almost
      independent of the SDS concentration. However, above the cmc there is a rapid
      decrease in the diffusion coefficients, and the apparent diffusion coefficients
      of the two solutes are the weighted average of free solute diffusion and the
      micelle diffusion. A model is presented to describe the diffusion behavior of the
      two solutes in aqueous micellar solutions of SDS. The interaction between the two
      solutes and the micelles has been investigated and the fraction of each solute
      that is solubilized by the micelles is estimated from the measured apparent
      diffusion coefficient. For benzoic acid, the diffusion coefficient is dependent
      on the joint contribution of the benzoic acid molecules that are solubilized by
      the micelles as well as the corresponding benzoate ions. The effect of micelle
      formation on the diffusion coefficient of benzoic acid is not as pronounced as
      for phenol and toluene. Copyright 2000 Academic Press.

PMID- 10942542
TI  - Thermal and Structural Behavior of Milk Fat.
AB  - The thermal and structural properties of unstable varieties of triacylglycerols
      (TGs) crystallizing in milk fat globules of cream are examined in the range -8-
      +50 degrees C using a new instrument allowing simultaneously time-resolved
      synchrotron X-ray diffraction at both wide and small angles as a function of
      temperature (XRDT) and high sensitivity differential scanning calorimetry (DSC).
      Small angle X-ray diffraction shows that the unstable alpha form first formed by
      cream quenching to -8 degrees C corresponds in fact to two different lamellar
      phases corresponding to 2L (47 A) and 3L (70.4 A) arrangements of TGs. The
      bilayered structure is very unstable since it disappears during the course of a
      20-min isothermal conditioning at -8 degrees C. On fast heating, the crystalline
      evolution of cream TGs demonstrates the monotropic character of their
      polymorphism. The structural and thermal behaviors of cream which are compared to
      that of its anhydrous milk fat isolated from the cream (C. Lopez et al., J. Dairy
      Sci., submitted) show that the crystallization occurring in emulsion droplets is
      similar to bulk. However, the comparison of XRD peak widths indicates that the TG
      crystallization is more disordered in emulsion. This disorder is attributed to
      the constraints due to the interface curvature in emulsion droplets. Copyright
      2000 Academic Press.

PMID- 10942543
TI  - Micellar Interactions in Nonionic/Ionic Mixed Surfactant Systems.
AB  - To study the influence of the chemical nature of headgroups and the type of
      counterion on the process of micellization in mixed surfactant systems, the cmc's
      of several binary mixtures of surfactants with the same length of hydrocarbon
      tail but with different headgroups have been determined as a function of the
      monomer composition using surface tension measurements. Based on these results,
      the interaction parameter between the surfactant species in mixed micelles has
      been determined using the pseudophase separation model. Experiments were carried
      out with (a) the nonionic/anionic C(12)E(6)/SDS ((hexa(ethyleneglycol) mono-n
      dodecyl ether)/(sodium dodecyl sulfate)), (b) amphoteric/anionic DDAO/SDS
      ((dodecyldimethylamine oxide)/(sodium dodecyl sulfate)), and (c)
      amphoteric/nonionic C(12)E(6)/DDAO mixed surfactant systems. In the case of the
      mixed surfactant systems containing DDAO, experiments were carried out at pH 2
      and pH 8 where the surfactant was in the cationic and nonionic form,
      respectively. It was shown that the mixtures of the nonionic surfactants with
      different kinds of headgroups exhibit almost ideal behavior, whereas for the
      nonionic/ionic surfactant mixtures, significant deviations from ideal behavior
      (attractive interactions) have been found, suggesting binding between the head
      groups. Molecular orbital calculations confirmed the existence of the strong
      specific interaction between (1) SDS and nonionic and cationic forms of DDAO and
      between (2) C(12)E(6) and the cationic form of DDAO. In the case for the
      C(12)E(6)/SDS system, an alternative mechanism for the stabilization of mixed
      micelles was suggested, which involved the lowering in the free energy of the
      hydration layer. Copyright 2000 Academic Press.

PMID- 10942544
TI  - Surface Chemical Studies on Pyrite in the Presence of Polysaccharide-Based
      Flotation Depressants.
AB  - The interaction of dextrin and guar gum with pyrite has been investigated through
      adsorption, flotation, and electrokinetic measurements. The adsorption densities
      of the polysaccharides onto pyrite reveal a region of higher adsorption density
      in the pH range 7.5-11, with a maximum around pH 10 for both polymers. The
      isotherms exhibit Langmuirian behavior. The adsorption density of guar gum onto
      pyrite is higher than that of dextrin. Electrokinetic measurements indicate a
      decrease in the electrophoretic mobility values in proportion to the
      concentration of the polymer added. Co-precipitation tests confirm polymer-ferric
      species interaction in the bulk solution, especially in the pH range 5.5-8.5. The
      pH range for higher adsorption, significant co-precipitation, and appreciable
      depression of pyrite encompass each other. XPS and FTIR spectroscopic studies
      provide evidence in support of chemical interaction between hydroxylated pyrite
      and the hydroxyl groups of the polymeric depressants. Copyright 2000 Academic
      Press.

PMID- 10942545
TI  - Geometrical Description of Contact Line Fluctuations in Heterogeneous Systems
      with Controlled Wettability.
AB  - The understanding of contact line fluctuations in heterogeneous systems of
      controlled wettability is relevant to many industrial processes. Despite its
      importance, it is poorly understood. Here, we present results on an experimental
      study of fluid displacement on modified Hele-Shaw cells with surface defects as
      heterogeneities. The system wettability is controlled by defect surface coverage.
      Three different surface coverage regimes were studied. For each one, the
      morphology and deformation energy of the displacement front is determined. The
      width front is described in terms of two exponents, the roughness exponent
      (alpha) and the one that describes its growth (beta). In all cases, it is found
      that the width increases logarithmically in time up to a characteristic value,
      where a crossover to a saturation behavior is observed. The crossover time is a
      function of the surface coverage. For low coverage 0.51</=beta</=0.59 and
      0.65</=alpha</=0.67. For medium and high coverage the values obtained for the
      exponents are similar to those of directed percolation. The deformation energy
      associated with the displacement front morphology makes it possible to identify
      the individual pinning role of the surface defects. Copyright 2000 Academic
      Press.

PMID- 10942546
TI  - An Exact Solution to the Electrostatic Interaction between an Ion-Penetrable
      Sphere and an Ion-Penetrable Rod.
AB  - No exact solution for the free energy of electrostatic interaction for a charged
      sphere and rod geometry in an electrolyte solution has yet been proposed. This
      geometry is interesting because it can be applied to describe macromolecules
      interacting with a random fiber-matrix for modeling of hindered transport in
      diffusional systems. Here we present an analytical approach that yields an exact
      solution to the problem for ion-penetrable-also called "soft"-sphere and
      infinitely long rod. This solution is compared to a published finite-element
      analysis of the same system with nonpenetrable-also called "hard"-sphere and
      infinitely long rod maintaining a constant surface charge density restriction.
      For any ionic strength or ratio of rod radius to sphere radius the ion-penetrable
      method yields an electrostatic free energy of interaction which is lower than
      that given by the analysis for hard bodies. This free energy is significantly
      lower for most parameter value combinations and therefore suggests that one
      should carefully examine the system being modeled to determine if it is
      approximated better by a hard body or ion-penetrable body approach. Copyright
      2000 Academic Press.

PMID- 10942547
TI  - Rheological and Electrokinetic Properties of Sodium Montmorillonite Suspensions.
AB  - In this article, we describe the rheology of Na montmorillonite suspensions as a
      function of pH, at constant ionic strength. The observed behavior is discussed
      quantitatively in terms of the potential energy of interaction between particles,
      keeping in mind the anisotropic nature of clay particles. The extended DLVO model
      that includes electrostatic, van der Waals, and polar acid-base contributions to
      the total energy is used. It is found that face-to-face interactions are
      virtually independent of pH, whereas edge-to-edge interactions are most
      attractive at the isoelectric point of edges (pH approximately 7). The most
      significant variations occur in face-to-edge potential energy, with strong
      attractions at pH<7. Steady-state viscometry showed that the yield stress
      decreases up to an order of magnitude between pH 3 and pH 7, with a much slower
      rate of decrease in the 7-11 pH interval. Concerning oscillatory measurements, it
      is found that both the elastic (G') and viscous (G") moduli are practically
      independent of frequency. It is also demonstrated that G'>G", the difference
      being larger at acid pH values. These results, in addition to potential energy
      calculations, suggest the existence of an elastic, coagulated structure up to pH
      7, whereas as the pH is increased such structure is more relaxed because of
      electrostatic repulsions. Similar conclusions are reached when creep-recovery
      data are analyzed. Copyright 2000 Academic Press.

PMID- 10942548
TI  - Rheological and Electrokinetic Properties of Sodium Montmorillonite Suspensions.
AB  - Because of their particular electric surface properties and crystal structure,
      most clay minerals possess a very high ion exchange capacity. Furthermore, the
      surface charge distribution is anisotropic: while faces of the laminar clay
      particles have a negative, pH-independent charge, edges may be positive or
      negative, depending on pH. In this work, we propose to contribute new data on
      particle-particle interaction and charge distribution, by means of measurements
      of the low-frequency dielectric dispersion (LFDD) of the clay suspensions.
      Because of the nonspherical shape of clay particles, there are no theoretical
      models capable of explaining the experimental relaxation spectra. Hence, we limit
      ourselves to obtaining indirect information by comparing LFDD spectra in
      different experimental conditions. The quantities of interest in LFDD are the
      value of the low-frequency dielectric constant, epsilon'(r)(0), and the
      characteristic or relaxation frequency, omega(cr). These two parameters were
      measured varying the weight fraction, straight phi, of clay (0.5, 1, and 1.5%
      w/v) and the pH of the dispersion medium (5, 7, and 9), while maintaining the
      ionic strength constant ([NaCl]=10(-4) M). It was found that the characteristic
      relaxation frequency of the dielectric constant was pH-dependent, with a
      significant minimum at pH 7 in all cases. The results are interpreted as the
      superposition of two independent relaxation phenomena, associated with edges and
      faces. With respect to the weight fraction influence, we have found a linear
      behavior of epsilon'(r)(0) with straight phi at pH 9, indicating the existence of
      no significant interaction between particles. However, at pH 7 a slight deviation
      of linearity is observed, and at pH 5 we observe a clearly nonlinear behavior,
      indicating a stronger degree of interaction between particles. This is in good
      agreement with the initial assumption that at acid pH values, the electric
      surface charge of faces is negative, whereas the edges possess a positive charge,
      thus favoring attractive face-to-edge interaction. Copyright 2000 Academic Press.

PMID- 10942549
TI  - Forces between Carboxylic Acid Surfaces in Divalent Electrolyte Solutions.
AB  - The behavior of self-assembled monolayers of thiohexadecanoic acid adsorbed onto
      gold interacting in asymmetric 2:1 electrolytes has been studied with direct
      force measurements. The effects of two divalent cations (Mg(2+) and Ca(2+)) were
      studied at concentrations ranging from 1 uM to 10 mM. As compared to interactions
      in the presence of Na(+), the divalent ions adsorb strongly to the surfaces, with
      the effect of lowering the surface potential and decreasing the double-layer
      repulsion. At concentrations above 10 uM, the Ca(2+) ions were found to adsorb
      stronger than Mg(2+). Ca(2+) ions cause charge reversal at high concentrations,
      and the net interactions at 10 mM were attractive over the measurable range.
      Copyright 2000 Academic Press.

PMID- 10942550
TI  - Polydispersity during the Formation and Growth of the Stober Silica Particles
      from Small-Angle X-Ray Scattering Measurements.
AB  - The early stages of formation of Stober silica particles have been investigated
      in situ during the hydrolysis and condensation of tetraethylorthosilicate under
      base-ammonia conditions in different alcoholic solvents. Time-resolved ultra
      small-angle X-ray scattering by the entities produced in the solutions is used
      for structural characterization and monitoring of the growth kinetics of the
      particles. Our primary focus is to assess the polydispersity of the formed
      colloidal particles and its evolution as a function of time. We first applied a
      maximum entropy analysis of the scattering data to determine the size
      distribution and the time evolution of the size distribution of the colloidal
      particles. Second, we extended the cumulant method to analyze our earlier small
      angle X-ray scattering data (H. Boukari, J. S. Lin, and M. T. Harris, J. Colloid
      Interface Sci. 194, 311, 1997; Chem. Mater. 9, 2376, 1997) and search for the
      presence of a distribution of fractal particles. The maximum entropy analysis
      indicates that there is a continuous nucleation of particles during the
      synthesis, and that this takes place within a relatively narrow size
      distribution. The cumulant analysis shows that, except at later times, the data
      are not adequate to confirm conclusively the presence of a distribution of
      fractal dimension at any time during the experiment. We discuss the impact of
      these results on growth kinetic models proposed for this system. Copyright 2000
      Academic Press.

PMID- 10942551
TI  - Sedimentation Potential and Velocity in a Concentrated Suspension of Soft
      Particles.
AB  - A theory of sedimentation in a concentrated suspension of spherical soft
      particles (i.e., polyelectrolyte-coated particles) is developed to obtain general
      expressions for sedimentation velocity of soft particles and sedimentation
      potential in the suspension. An Onsager relation between sedimentation potential
      and electrophoretic mobility of spherical soft particles in concentrated
      suspensions is derived for the case of low potentials and nonoverlapping
      electrical double layers of adjacent particles. Copyright 2000 Academic Press.

PMID- 10942552
TI  - Initial Stage Dynamics of Bridging Flocculation of Polystyrene Latex Spheres with
      Polyethylene Oxide.
AB  - The kinetics of bridging flocculation of polystyrene latex (PSL) particles
      induced by addition of excess polyethylene oxide (PEO) in the initial stage was
      studied using standardized mixing flow generated in an end-over-end rotation
      apparatus. To clarify the effect of the rate of polymer supply, flocculation
      experiments were performed by changing polymer concentration (C(p)). As was found
      in previous investigation, the progress of flocculation is divided into two
      stages. The first stage is characterized by an enhancement of the rate of
      flocculation by polymer addition. The increase in polymer concentration results
      in a higher enhancement but in a shorter duration for this stage. In the second
      stage, the flocculation is essentially stopped due to the appearance of steric
      stabilization. It was found that the ultimate degree of flocculation goes through
      a maximum against C(p). That is, when C(p)>==1.0 ppm, the ultimate degree of
      flocculation decreases with increased C(p). In this region, a clear crossover
      from the first stage to the second stage was observed. In the extreme case,
      evidence of a slight setback of flocculation was confirmed, which implies the
      breakup of metastable bridges by the application of additional fluid shear. When
      C(p)<==1.0 ppm, the ultimate degree of flocculation decreases with decreased
      C(p). The crossover from the first stage to the second stage appears more gradual
      at lower C(p). These results were observed irrespective of ionic strength. This
      result was interpreted as the elimination of a bare surface due to the spreading
      of a steric layer of adsorbed polymer. The characteristic time for reconformation
      of the polymer at a bare colloidal surface was estimated to be a few seconds.
      Copyright 2000 Academic Press.

PMID- 10942553
TI  - Dynamics of Wetting.
AB  - We consider the dynamics of spreading of a small drop over a smooth solid
      surface. The analysis is concerned with complete wetting and accounts for
      capillary, viscous, and van der Waals effects, with two spreading geometries
      considered: cylindrical and axisymmetric. A complete description of the drop
      thickness, slope, and curvature profiles is provided. The model is not based on
      any fitting parameter, and the spreading laws are found to be in good agreement
      with published data obtained by different experimental techniques. The study
      evaluates the relative magnitudes of capillary, viscous, and disjoining-pressure
      effects and discusses the asymptotic form of the film profile and the existence
      of a singularity at the three-phase contact line. The model allows determination
      of the complete distribution of viscous dissipation in the whole drop, and the
      rate of viscous dissipation is related to the losses of the liquid drop free
      energy. Copyright 2000 Academic Press.

PMID- 10942554
TI  - Solution Properties of Star-Shaped Polystyrenes Having Peripheral Charged Ions.
AB  - Functionalized polystyrene stars were prepared by copolymerization of polystyryl
      lithium with divinylbenzene in a mixture of benzene/tetrahydropyran, where the
      polystyrene arms were prepared by anionic polymerization using [2-[(N,N
      dimethylamino)-methyl]phenyl]lithium as the initiator. These functional stars
      were converted by quaternization with methyl iodide into polystyrene stars having
      peripheral positive charges. We studied the charge effects on the solution
      properties of such stars. The hydrodynamic dimension of peripheral charged
      polystyrene (PS) stars depended strongly on the solubility parameter between PS
      segments and solvent. Copyright 2000 Academic Press.

PMID- 10942555
TI  - Diffusion Effects in the Wetting of a Contaminated Surface.
AB  - Industrial wetting situations often involve the presence of a third component
      near an interface, potentially modifying the local effective capillary balance.
      We here consider a simplified situation in which a drop is placed on a substrate
      supporting a thin layer of "contamination." As spreading of the drop to
      equilibrium occurs, the contaminant diffuses into the drop, modifying the
      effective substrate/drop interfacial free energy (increasing it, it is assumed).
      Thus the kinetics of spreading are altered. The essential effect when the final
      equilibrium contact angle is zero is that of accelerating the process. However,
      when the final value of contact angle is finite, "overshoot" may occur. The drop
      spreads beyond its equilibrium state and then retracts to attain its equilibrium
      state asymptotically at long times. Copyright 2000 Academic Press.

PMID- 10942556
TI  - An Improved Method for Calculating Zeta-Potentials from Measurements of the
      Electrokinetic Sonic Amplitude.
AB  - The surface electric properties of the commercially available silica, Monospher
      1000 (Fa. Merck), have been studied by conductivity and ESA (electrokinetic sonic
      amplitude) experiments. It could be shown that accounting for the contribution of
      the stagnant layer to surface conductivity is indispensable in the interpretation
      of electrokinetic data at low ionic strength. A general method has been put
      forward which allows to take into account the total, experimentally accessible
      surface conductivity in the evaluation of ESA data of moderately concentrated
      suspensions. This includes additional conductivity measurements which serve for
      the independent estimation of the total relative surface conductivity. The
      resulting zeta-potentials are clearly higher than those obtained after neglecting
      the contribution of the stagnant layer to surface conductivity. In addition, the
      ionic mobilities of potassium and magnesium in the hydrodynamically stagnant
      layer have been investigated in some detail. It has been found that the ionic
      mobility of potassium is of the same order of magnitude as in the bulk solution
      while the mobility of magnesium is significantly reduced. Copyright 2000 Academic
      Press.

PMID- 10942557
TI  - Drag and Torque on Clusters of N Arbitrary Spheres at Low Reynolds Number.
AB  - Hydrodynamics of particle clusters suspended in viscous fluids is a subject of
      considerable theoretical and practical importance. Using a multipole expansion of
      the flow velocity in a series of spherical harmonics, Lamb's fundamental solution
      of the Stokes flow outside a single sphere is generalized in this work to the
      case of N nonoverlapping spheres of arbitrary size with slip boundary conditions.
      The expansion coefficients are found by transforming the boundary conditions to
      the Lamb form and by transforming the spherical coordinates and solid spherical
      harmonics centered at different spheres. The problem is reduced to the solution
      of the linear system of equations for the expansion coefficients, which is
      carried out numerically. Based on the developed theory, the relation between the
      hydrodynamic and gyration radius of fractal-like aggregates with different
      structure is established. In another application, an asymptotic slip-regime
      dependence of the aggregate hydrodynamic radius on the Knudsen number and the
      number of particles is found by performing calculations of drag forces acting on
      the gas-borne fractal-like and straight chain aggregates. A good agreement is
      shown in comparing predictions of the described theory with available
      experimental and theoretical results on motion of various small sphere clusters
      in viscous fluid. Copyright 2000 Academic Press.

PMID- 10942558
TI  - Biosorption of Heavy Metal Ions to A Marine Microalga, Heterosigma akashiwo
      (Hada) Hada.
AB  - A fundamental study of the application of marine microalga to the aqueous-phase
      separation of toxic heavy metals was carried out. The biosorption characteristics
      of cadmium and lead ions were determined with marine microalga, Heterosigma
      akashiwo (Hada) Hada, which was inactivated by steam sterilization. A simple
      metal-binding model was used for the description of metal-binding data. The
      results showed that the biosorption of bivalent metal ions to H. akashiwo was due
      to monodentate binding to two different types of acidic sites: carboxylic- and
      phosphatic-type sites. Copyright 2000 Academic Press.

PMID- 10942559
TI  - Electrolyte Anion Affinity and Its Effect on Oxyanion Adsorption on Goethite.
AB  - The influence of various types of background electrolytes (NaCl, NaNO(3), and
      NaClO(4)) on the proton adsorption and on the adsorption of sulfate and phosphate
      on goethite have been studied. Below the PZC the proton adsorption on goethite
      decreases in the order Cl>NO(3)>ClO(4). The decreasing proton adsorption affects
      the adsorption of oxyanions on goethite. Anion adsorption of strongly binding
      polyvalent anions is lower in the studied electrolytes in the order
      Cl<NO(3)<ClO(4). The ion pair formation constants of monovalent electrolyte
      anions on the goethite surface are derived from proton adsorption data. It is
      shown that the derived ion pair formation constants enable the prediction of the
      effect of different electrolyte anions on adsorption of polyvalent anions.
      Especially at low oxyanion and high electrolyte concentrations the differences
      between the electrolytes influence the anion adsorption considerably. The effect
      is in principle not different for anions with a higher affinity for goethite,
      such as phosphate in comparison with sulfate, but the effect is only there if the
      particles are positively charged, which in the case of phosphate is only the case
      at relatively low P concentration and sufficiently low pH values. Copyright 2000
      Academic Press.

PMID- 10942560
TI  - Preparation of Micrometer Size Budesonide Particles by Precipitation.
AB  - Particles of different shape, size and crystallinity of budesonide, a
      hydrocortisone streroid, were prepared by precipitation. The method is based on
      taking advantage of the different solubility of this material in certain organic
      solvents (ethanol, acetone) and water or alcanes. In principle, to solutions of
      budesonide, water was added until the solids precipitate or the same solute in
      mixed solvents was carefully separated by evaporation of the more volatile
      component at room temperature. The morphology, size, and stability of the
      resulting particles were sensitive to the evaporation technique, stirring, and
      presence of a stabilizing agent. Copyright 2000 Academic Press.

PMID- 10942561
TI  - Intermediates Produced in the Electron-Transfer Processes of
      Phenothiazine/Semiconductor Systems.
AB  - Phenothiazine radical cation PTH(+*) and phenothiazine dication PTH(2+) produced
      by photoinduced electron transfer in phenothiazine/semiconductor systems have
      been studied by using ESR, UV-visible absorption, and fluorescence spectroscopic
      methods. It is found that the PTH(+*) was generated by electron transfer from
      (1)PTH* and (3)PTH* to the conduction band of the semiconductors besides PTH(+*)
      resulted in the photoionization of PTH as well as PTH(2+) produced by electron
      transfer from PTH(+*) to the conduction band of the semiconductors successively.
      Very significant supplementary information provided by UV-visible absorption,
      ESR, and resonance Raman spectra of PTH(+*) and PTH(2+), which were obtained by
      oxidation of PTH with lead tetraacetate, not only confirmed the two-step mono
      electron-transfer mechanism proposed for interpretation of electron-transfer
      processes in PTH/semiconductor systems but also demonstrated that the two
      successive electron-transfer steps were corresponding to the removal of a p
      electron at the nitrogen atom and a p-electron at the sulfur atom in the PTH
      molecule, respectively. Consequently, the nonplanar configuration of the PTH
      molecule changed into a planar configuration of the PTH(2+). Copyright 2000
      Academic Press.

PMID- 10942562
TI  - Templated Synthesis of CdS/PAN Composite Nanowires under Ambient Conditions.
AB  - CdS/PAN (polyacrylonitrile) composite nanowires were prepared by templated
      synthesis under ambient conditions, using a 4 : 1 (v/v) distilled water-isopropyl
      alcohol solvent mixture and Na(2)S(2)O(3) as sulfur source. Transmission electron
      microscopy images showed typical CdS/PAN nanowires with diameters less than 6 nm
      and lengths from 200 nm to 1 um. CdS/PAN nanowires were also characterized by FT
      infrared spectra (FTIR), X-ray powder diffraction (XRD) patterns, and UV-vis
      spectra. It is found that the feed mole ratio of CdCl(2) to AN exerts a
      significant influence on the formation and morphology of CdS/PAN nanowires. In
      addition, possible mechanism of the reactive process was presented. Copyright
      2000 Academic Press.

PMID- 10942563
TI  - Kinetics of the Formation and Dissolution of Ni Precipitates in a
      Gibbsite/Amorphous Silica Mixture.
AB  - There have been a number of studies that have examined metal precipitation
      reactions on an array of natural soil materials. While many of these
      investigations have focused on model single-component systems, recent research
      has appeared on metal precipitation on soils and clay fractions of soils.
      However, few studies have explored mixed model component systems, which may lead
      to a better understanding of metal reactions on soils and clay fractions.
      Furthermore, only a few studies have appeared on the stability of the metal
      surface precipitates. In light of this, we investigated Ni sorption and
      dissolution kinetics and mechanisms on a mixture of gibbsite and amorphous silica
      by combining macroscopic studies with X-ray absorption fine structure (XAFS) and
      diffuse reflectance spectroscopies (DRS), and high-resolution thermogravimetric
      analysis (HRTGA). Batch sorption experiments were conducted at pH 7.5 and at
      different reaction times to elucidate the sorption process and to study the role
      of residence time on metal precipitate stability. Spectroscopic and HRTGA
      investigations revealed alpha-Ni(OH)(2) precipitates formed on the
      gibbsite/silica mixture initially and over time evolved to a Ni phyllosilicate.
      The available Si source was derived from partial dissolution of the sorbent
      during Ni sorption. With increasing residence time, the precipitate phases
      drastically increased in stability, as shown by decreasing amounts of Ni release
      as effected by nitric acid (HNO(3)) and ethylenediaminetetraacetic acid (EDTA)
      treatments. This aging effect may be explained by the silicate-for-nitrate
      exchange during the first days of reaction and subsequently by silicate
      polymerization and partial grafting onto the hydroxide layers to form a
      phyllosilicate precursor phase (R. G. Ford, A. C. Scheinost, K. G. Scheckel, and
      D. L. Sparks, Environ. Sci. Technol. 33(18), 3140-3144, 1999). Copyright 2000
      Academic Press.

PMID- 10942564
TI  - Thermodynamics of Chromium(VI) Anionic Species Sorption onto Surfactant-Modified
      Montmorillonite Clay.
AB  - Batch sorption experiments performed on Cr(VI) species sorption showed a
      significantly enhanced removal of inorganic hexavalent chromium anionic species
      from aqueous solution by montmorillonite clays modified with quaternary amine,
      hexadecyltrimethylammonium (HDTMA) bromide. Unmodified clay had no affinity for
      chromium(VI) species. The sorption of Cr(VI) species has been carried out as a
      function of pH, contact time, adsorbate concentration (4.14x10(-5) to 8.62x10(-3)
      M), and temperature (5-45 degrees C). The surfactant-modified clay surface was
      stable when exposed to extremes in pH. The optimum pH for maximum sorption of
      Cr(VI) species was found to be at pH 1 and was constant between pH 2 and pH 6.
      The sorption data obtained was well described by DKR and Langmuir sorption
      isotherms. Sorption energy (E) for (i) surfactant sorption by montmorillonite
      clay and (ii) sorption of chromium(VI) species by surfactant modified clay have
      been computed from the DKR equation. Sorption energy evaluated for the sorption
      of both surfactant and Cr(VI) species showed that an ion-exchange mechanism was
      operative. The mechanism of retention appears to be replacement of counterion of
      the surfactant by Cr(VI) anionic species. Adsorbent capacity for the sorption of
      Cr(VI) species has been evaluated from the Langmuir sorption isotherm data.
      Thermodynamic parameters (Delta H degrees, Delta S degrees and Delta G degrees )
      for surfactant sorption on montmorillonite clay and Cr(VI) sorption by modified
      clay have been evaluated. The specific rate constant for sorption of Cr(VI)
      species on modified montmorillonite was rapid during the first 10 min and
      equilibrium was found to be attained within 30 min. The sorption of Cr(VI)
      species onto modified montmorillonite clay followed first-order rate kinetics.
      Copyright 2000 Academic Press.

PMID- 10942565
TI  - Adsorption Behavior of Amino Acids on a Stainless Steel Surface.
AB  - The adsorption behavior of various amino acids on a stainless steel surface was
      investigated at 30 degrees C and over a pH range of 3-10. Acidic and basic amino
      acids except histidine adsorbed remarkably at pH 3-4 and 7-10, respectively, and
      showed Langmuir-type adsorption isotherms. The effects of pH and ionic strength
      on the adsorption isotherms were investigated to analyze the interactions between
      amino acids and adsorption sites on the stainless steel. Hydrophobic amino acids
      and glycine showed only small adsorbed amounts at all pHs tested. For the acidic
      and basic amino acids, reversibility of the absorption and the influence of the
      ionic strength on the adsorption behavior were examined. The adsorption isotherms
      of the derivatives of aspartic acid were also measured in order to examine the
      contribution of the carboxylic groups of acidic amino acids to the adsorption.
      Furthermore, a Fourier-transform infrared spectroscopic analysis and
      semiempirical molecular orbital calculation were carried out to analyze the
      ionization states and the configuration of the amino acids adsorbed on a
      stainless steel surface. These investigations suggest that the acidic and basic
      amino acids adsorb through two electrostatic interactions of two ionized groups
      in the amino acid with a stainless steel surface. Copyright 2000 Academic Press.

PMID- 10942566
TI  - Rates of Mass Transfer and Adsorption of Hexadecyltrimethylammonium Bromide at an
      Expanding Air-Water Interface.
AB  - An overflowing cylinder (OFC) provides a convenient method for studying
      nonequilibrium liquid interfaces under steady-state conditions. In the presence
      of surfactants in solution, large accelerations in the surface velocity are
      observed as a result of Marangoni effects. The surface expansion rate is
      approximately uniform over the surface of the OFC and falls in the range of 1-10
      s(-1). In this paper, a quantitative model is presented for the mass transport to
      the expanding surface of the OFC. The model is then used to analyze experimental
      measurements of surface expansion rates and surface excess for solutions of a
      cationic surfactant, hexadecyltrimethylammonium bromide (CTAB), obtained by laser
      Doppler scattering and neutron reflection, respectively. The experimental results
      are in satisfactory agreement with the predictions of diffusion-controlled
      adsorption close to the critical micelle concentration (cmc). At concentrations
      well above and well below the cmc, kinetic barriers to adsorption appear to
      exist. The data at low concentrations are discussed in terms of a model for mass
      transport through the electrical double layer. At high concentrations, double
      layer effects are negligible and steric barriers to adsorption are postulated.
      Copyright 2000 Academic Press.

PMID- 10942567
TI  - Use of Pyrene Spectroscopic Probes in the Study of Colloidal Systems.
AB  - The interfacial behavior of polyethylene oxide (PEO) end-labeled with the often
      used fluorescent probe pyrene was monitored to asess the effect of use of such
      hydrophobic probes on system behavior. Mixtures of labeled and unlabeled PEO were
      adsorbed on silica and the resulting suspension properties noted. The suspension
      behavior was found to be markedly different, depending on the ratio of labeled-to
      unlabeled PEO employed. While it was "safe" to use pyrene probes in amounts of 3%
      or less for spectroscopic investigation of PEO effects, it was found that ratios
      equal to, or greater than, 1 : 3 produced anomalous behavior of the silica
      suspensions. This was manifested in the form of decreased suspension stability,
      as evidenced by significantly higher settling rates. Similar experiments using
      free pyrene revealed that these effects could be attributed to the chemical
      attachment of the pyrene probe to the polyethylene oxide chain. Fluorescence
      spectroscopy was used to simultaneously monitor the behavior of the adsorbed
      polyethylene oxide molecules. These results were used to explain the observed
      suspension behavior as a function of the labeled-to-unlabeled polymer mixing
      ratio. Bridging effects facilitated by hydrophobic interaction between pyrene end
      groups is proposed as the reason for the observed phenomena. Copyright 2000
      Academic Press.

PMID- 10942568
TI  - Fractal-like Aggregates: Relation between Morphology and Physical Properties.
AB  - A number of modern technological applications require a detailed calculation of
      the physical properties of aggregated aerosol particles. For example, in probing
      soot aerosols by the method called laser-induced incandescence (LII), the soot
      clusters are suddenly heated by a short, powerful laser pulse and then cool down
      to the temperature of the carrier gas. LII sizing is based on rigorous
      calculation of the soot aggregate heat-up and cooling and involves prediction of
      laser light absorption and energy and mass transfer between aggregated particles
      and the ambient gas. This paper describes results of numerical simulations of the
      mass or energy transfer between the gas and fractal-like aggregates of N
      spherical particles in either the free-molecular or continuum regime, as well as
      the light scattering properties of random fractal-like aggregates, based on
      Rayleigh-Debye-Gans (RDG) theory. The aggregate geometries are generated
      numerically using specially developed algorithms allowing "tuning" of the fractal
      dimension and prefactor values. Our results are presented in the form of easily
      applicable scaling laws, with special attention paid to relations between the
      aggregate gyration radius and the effective radius describing various transport
      processes between the aggregates and the carrier gas. Copyright 2000 Academic
      Press.

PMID- 10942569
TI  - Film Drainage between Colliding Drops at Constant Approach Velocity: Experiments
      and Modeling.
AB  - Experiments and modeling of the drainage of the thin liquid film between two
      deformable spherical drops approaching each other at constant velocity in another
      liquid are being presented. Two numerical models based on the lubrication theory
      have been developed considering the cases of immobile or mobile drop interfaces.
      The absolute film thickness and the thinning rate have been measured using laser
      interferometry for a wide range of capillary numbers. In all studied cases, the
      model with immobile interfaces was found to give the best predictions of the
      experimental time evolution of the film thickness and radial expansion. These
      results made it possible to derive a typical time scale of the drainage process.
      Copyright 2000 Academic Press.

PMID- 10942570
TI  - Vibrational Spectroscopy Study of Selenate and Sulfate Adsorption Mechanisms on
      Fe and Al (Hydr)oxide Surfaces.
AB  - The coordination and speciation of selenate (SeO(4)) and sulfate (SO(4)) on
      goethite and Al oxide were studied using Raman and ATR-FTIR spectroscopy. Raman
      spectra were collected from pastes of suspensions containing 4 mM SeO(4) or
      SO(4). For SO(4), complementary data were collected by ATR-FTIR spectroscopy in
      goethite systems with 1 mM SO(4) and in Al oxide systems with 4 mM SO(4). The
      combined data set of Raman and ATR-FTIR spectra indicate that both inner- and
      outer-sphere surface complexes of SeO(4) and SO(4) occur on these metal
      (hydr)oxide surfaces. These spectral data show that SeO(4) and SO(4) have a
      similar complexation behavior on the same adsorbent. On goethite, these form
      predominantly monodentate inner-sphere surface complexes at pH <6, while at pH >6
      these anions exist predominantly as outer-sphere surface complexes. On Al oxide,
      in contrast, these anions exist predominantly as outer-sphere surface complexes,
      but a small fraction is also present as an inner-sphere complex at pH <6. A
      comparison of the spectral intensities of these anions on goethite and Al oxide
      shows that complexation of these anions with Al oxide is weaker than with Fe
      oxide. Copyright 2000 Academic Press.

PMID- 10942571
TI  - Comparative Study on the Structure of Water in Reverse Micelles Stabilized with
      Sodium Bis(2-ethylhexyl) Sulfosuccinate or Sodium Bis(2-ethylhexyl) Phosphate in
      n-Heptane.
AB  - The microstructure of water solubilized in H(2)O/surfactant/n-heptane ternary
      systems has been investigated by employing (1)H-NMR and FT-IR spectroscopic
      techniques. Two reverse micellar systems were prepared and studied, i.e., sodium
      bis(2-ethylhexyl) sulfosuccinate in n-heptane (H(2)O/AOT/n-heptane) and sodium
      bis(2-ethylhexyl) phosphate in n-heptane (H(2)O/NaDEHP/n-heptane). (1)H-NMR data
      showed that the chemical shift of water protons for the AOT and NaDEHP reverse
      micelles varied downfield and upfield, respectively, with an increase of the
      water content. The opposite shift directions with increasing water content are
      interpreted as due to a composition change of the solubilized water associated
      with head-groups and sodium counterions in reverse micellar systems. On the basis
      of deconvolution results of FT-IR spectra, a four-component model is proposed to
      interpret the FT-IR and (1)H-NMR results. Copyright 2000 Academic Press.

PMID- 10942572
TI  - Preparation of Hydrophobically Modified Poly(amidoamine) Dendrimer-Encapsulated
      Gold Nanoparticles in Organic Solvents.
AB  - HAuCl(4) in aqueous solution was extracted to toluene or chloroform using a
      hydrophobically modified poly(amidoamine) dendrimer. Then, by reduction of Au(3+)
      ions with dimethylamineborane, gold nanoparticles in the size range of 2-4 nm
      were obtained in toluene or chloroform. It is suggested that gold nanoparticles
      are encapsulated by the dendrimer. Copyright 2000 Academic Press.

PMID- 10942573
TI  - Electrical Conductivity of a Concentrated Suspension of Soft Particles.
AB  - A general expression for the electrical conductivity of a concentrated suspension
      of spherical soft particles (polyelectrolyte-coated particles) is obtained for
      the case where the overlapping of the electrical double layers of adjacent
      particles is negligible by using Kuwabara's cell model. It is shown that in the
      limit of very low potentials the obtained conductivity expression reduces to
      Maxwell's relation with respect to the volume fraction of the particle core and
      the contribution from the polyelectrolyte layer becomes negligible. An
      approximate conductivity expression is derived for the case of low potentials.
      Copyright 2000 Academic Press.

PMID- 10942574
TI  - Transcriptional activation of the granulocyte-macrophage colony-stimulating
      factor receptor gene in cell mutants.
AB  - Retroviral insertional mutagenesis has proven to be a powerful in vivo approach
      for identifying genetic mutations involved in tumorigenesis or developmental
      abnormalities. Applying this approach to an in vitro system, where experimental
      design can be readily manipulated, would greatly increase its efficacy. In this
      study, we sought to determine whether retroviral insertional mutagenesis could be
      used to isolate cell mutants, in which the transcriptional activation of a
      receptor gene has occurred. Cells of the myeloid progenitor cell line FDC-P1(M),
      which do not express the alpha receptor subunit (GMRalpha) for granulocyte
      macrophage colony-stimulating factor (GM-CSF), were infected and selected for
      growth in GM-CSF. Over 100 mutants were isolated at a frequency up to ninefold
      higher than that of uninfected controls. Expression of GMRalpha in these mutants
      was confirmed by blocking proliferation with GM-CSF antibodies, detection of high
      affinity receptors, and Northern blot analysis. Significantly, in 7/18 mutants
      analyzed, gross DNA rearrangements had occurred in the GMRalpha locus. These
      rearrangements were demonstrated to be due to intergenic rearrangements,
      juxtaposing an active enhancer/promoter upstream of the GMRalpha gene. In one
      mutant it could be demonstrated that the wild-type allele was also expressed,
      providing evidence that secondary mutations had occurred. The implications of
      these results for retroviral insertional mutagenesis are discussed.

PMID- 10942575
TI  - Association between the calcium-binding protein calretinin and cytoskeletal
      components in the human colon adenocarcinoma cell line WiDr.
AB  - Calretinin (CR) is a Ca(2+)-binding protein (CaBP) of the EF-hand family
      expressed in a cell-type-specific manner and thought to act as a Ca(2+) buffer.
      Based upon previous studies, CR can undergo Ca(2+)-induced conformational
      changes, suggesting that it may also belong to the subfamily of Ca(2+)-sensor
      proteins that are characterized by their ability to interact with target ligands.
      To elucidate the role of CR, we used the undifferentiated colon adenocarcinoma
      cell line WiDr, which expresses significant amounts of CR. It has been shown
      previously that combined treatment with an inducer of differentiation sodium
      butyrate (NaBt) and a cell growth inhibitor hexamethylene bisacetamide (HMBA) or
      treatment with CR antisense oligonucleotides is down-regulating CR in parallel
      with a decrease of cell growth, suggesting a possible involvement of CR in
      maintaining the undifferentiated phenotype of WiDr cells. Furthermore, CR is
      absent from normal colon cells and from well-differentiated colon adenocarcinoma
      cell lines (e.g., Caco-2). Since members of the EF-hand family of proteins are
      interacting with cytoskeletal components, we investigated the possible
      association of CR with the cytoskeleton in WiDr cells. With double
      immunofluorescence stainings and immunoprecipitation experiments, we show close
      association of CR with intermediate filaments or microtubules in WiDr cells.
      Treatment with NaBt either disrupted or strongly diminished this interaction,
      respectively. The same effect was observed after elevation of [Ca(2+)](i) by
      applying the ionophore A-23187. These data suggest that CR may contribute to the
      transformation of enterocytes by interfering with the differentiation process,
      i.e., acting at both levels: cell shape dynamics and mitosis.

PMID- 10942576
TI  - Spermine oxidation leads to necrosis with plasma membrane phosphatidylserine
      redistribution in mouse leukemia cells.
AB  - Oxidation by copper/quinone-containing serum amine oxidases (SAO) is a well-known
      cause of polyamine cytotoxicity. Spermine oxidation exerts potent
      immunosuppressive effects in animal cells, but the cell death mechanism involved
      remains unclear. We compared biochemical and morphological parameters of SAO
      mediated cell death in L1210 mouse leukemia cells with normal or amplified
      ornithine decarboxylase gene expression with those observed during apoptosis
      induced by deregulated polyamine uptake or by okadaic acid. None of the
      characteristic features of apoptotic cell death (e.g., chromatin condensation,
      nuclear fragmentation, internucleosomal DNA cleavage, poly(ADP-ribose) polymerase
      cleavage) were observed during spermine oxidation-mediated cell death, which was
      clearly necrotic by morphological criteria. Inhibition of a wide spectrum of
      caspases did not prevent SAO-dependent cell death, whereas N-acetylcysteine
      completely abolished the cytotoxic effects of spermine oxidation. Catalase only
      delayed spermine oxidation-induced cell death without affecting its modality or
      preventing depletion of intracellular glutathione, suggesting that both H(2)O(2)
      and aminoaldehydes generated by SAO-mediated spermine oxidation contribute to SAO
      induced necrosis. Interestingly, redistribution of phosphatidylserine to the
      outer leaflet of the plasma membrane, usually a diagnostic feature of apoptosis,
      preceded necrotic cytolysis triggered by spermine oxidation. Thus, L1210 cell
      death caused by SAO-mediated spermine oxidation has all the attributes of primary
      necrosis, but is also accompanied by loss of phospholipid asymmetry, indicating
      that the latter phenomenon may not be unique to apoptosis. Phosphatidylserine
      exposure, a potent engulfment signal for phagocytes, might contribute to the
      immunosuppressive effects of plasma polyamines through a controlled and rapid
      necrotic process involving SAO.

PMID- 10942578
TI  - Bioactive motifs of agouti signal protein.
AB  - The switch between the synthesis of eu- and pheomelanins is modulated by the
      interaction of two paracrine signaling molecules, alpha-melanocyte stimulating
      hormone (MSH) and agouti signal protein (ASP), which interact with melanocytes
      via the MSH receptor (MC1R). Comparison of the primary sequence of ASP with the
      known MSH pharmacophore provides no suggestion about the putative bioactive
      domain(s) of ASP. To identify such bioactive motif(s), we synthesized 15-mer
      peptides that spanned the primary sequence of ASP and determined their effects on
      the melanogenic activities of murine melanocytes. Northern and Western blotting
      were used, together with chemical analysis of melanins and enzymatic assays, to
      identify three distinct bioactive regions of ASP that down-regulate
      eumelanogenesis. The decrease in eumelanin production was mediated by down
      regulation of mRNA levels for tyrosinase and other melanogenic enzymes, as occurs
      in vivo, and these effects were comparable to those elicited by intact
      recombinant ASP. Shorter peptides in those motifs were synthesized and their
      effects on melanogenesis were further investigated. The amino acid arginine,
      which is present in the MSH peptide pharmacophore (HFRW), is also in the most
      active domain of ASP (KVARP). Our data suggest that lysines and an arginine (in
      motifs such as KxxxxKxxR or KxxRxxxxK) are important for the bioactivity of ASP.
      Identification of the specific ASP epitope that interacts with the MC1R has
      potential pharmacological applications in treating dysfunctions of skin
      pigmentation.

PMID- 10942579
TI  - Cytoskeletal disruption accelerates caspase-3 activation and alters the
      intracellular membrane reorganization in DNA damage-induced apoptosis.
AB  - In actinomycin D (AD)-induced apoptosis, caspase-3 activation and DNA cleavage in
      human megakaryoblastic leukemia CMK-7 cells were greatly accelerated by tubulin
      and actin polymerization inhibitors [e.g., colcemid (CL) and cytochalasin D (CD),
      respectively], but the acceleration was not found with Taxol or phalloidin. A
      decrease in mitochondrial transmembrane potential, release of cytochrome c into
      the cytosol, and cleavage of procaspase-9 to its active form preceded the
      activation of caspase-3 and, moreover, all of these events began earlier and/or
      proceeded faster in cells treated with AD plus CL or CD than in cells treated
      with AD only. These results suggest that cytoskeletal disruption in the apoptotic
      cells promotes damage of the mitochondrial membrane, resulting in the enhanced
      release of cytochrome c necessary for the activation of caspase-9 that initiates
      the caspase cascade. On the other hand, apoptotic bodies were rapidly formed from
      cells treated with AD and CL, but were suppressed when treated with AD and CD.
      Intracellular membranes and the actin system were reorganized to surround the
      nuclear fragments in the AD- and CL-treated cells, but such a membrane system was
      not formed in the presence of CD, implying that the apoptotic bodies are formed
      via reorganization of intracellular membranes under regulation by actin
      polymerization. Thus, the cytoskeletal change in CMK-7 cells has a strong effect
      on the early biochemical process as well as on the later morphologic process in
      AD-induced apoptosis.

PMID- 10942577
TI  - Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced
      cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the
      retinoblastoma protein-related p107 protein.
AB  - The actin cytoskeleton has been found to be required for mitogen-stimulated cells
      to passage through the cell cycle checkpoint. Here we show that selective
      disruption of the actin cytoskeleton by dihydrocytochalasin B (H(2)CB) blocked
      the mitogenic effect in normal Swiss 3T3 cells, leading to cell cycle arrest at
      mid to late G(1) phase. Cells treated with H(2)CB remain tightly attached to the
      substratum and respond to mitogen-induced MAP kinase activation. Upon
      cytoskeleton disruption, however, growth factors fail to induce
      hyperphosphorylation of the retinoblastoma protein (pRb) and the pRb-related
      p107. While cyclin D1 induction and cdk4-associated kinase activity are not
      affected, induction of cyclin E expression and activation of cyclin E-cdk2
      complexes are greatly inhibited in growth-stimulated cells treated with H(2)CB.
      The inhibition of cyclin E expression appears to be mediated at least in part at
      the RNA level and the inhibition of cdk2 kinase activity is also attributed to
      the decrease in cdk2 phosphorylation and proper subcellular localization. The
      expression patterns of cdk inhibitors p21 and p27 are similar in both untreated
      and H(2)CB-treated cells upon serum stimulation. In addition, the changes in
      subcellular localization of pRb and p107 appear to be linked to their
      phosphorylation states and disruption of normal actin structure affects nuclear
      migration of p107 during G(1)-to-S progression. Taken together, our results
      suggest that the actin cytoskeleton-dependent G(1) arrest is linked to the cyclin
      cdk pathway. We hypothesize that normal actin structure may be important for
      proper localization of certain G(1) regulators, consequently modulating specific
      cyclin and kinase expression.

PMID- 10942580
TI  - Analysis of mtDNA copy number and composition of single mitochondrial particles
      using flow cytometry and PCR.
AB  - Mitochondrial DNA (mtDNA) is a multicopy, maternally inherited, genome.
      Individuals frequently carry a mixture of genetically distinct mtDNA molecules
      whose proportions may vary between sexual generations or among tissues from the
      same individual. Analyses of the genetic composition of mitochondria have
      previously relied on electron microscopy and have not permitted the genotype of
      single mitochondria to be determined. We have developed flow cytometry techniques
      to isolate single mitochondrial particles and PCR-based assays to determine the
      mtDNA copy number and composition of individual particles. In a first application
      of this method, we studied mitochondrial particles from fibroblast cells
      heteroplasmic for the tRNA lys(8344) point mutation, associated with myoclonus
      epilepsy and ragged red fiber (MERRF). Individual mitochondrial particles
      contained between 0 and 11 mtDNA molecules with a mean of 2.0 (95% CI 1.6-2.4).
      The majority (75%) of the mitochondrial particles from which a PCR product was
      obtained contained only one type of mtDNA, consistent with the low mean mtDNA
      copy number. The method developed may be applied to studies of the copy number
      and distribution of mtDNA genomes in different cell types.

PMID- 10942581
TI  - A detailed analysis of cyclin A accumulation at the G(1)/S border in normal and
      transformed cells.
AB  - The temporal relationship between cyclin A accumulation and the onset of DNA
      replication was analyzed in detail. Five untransformed and nine transformed
      asynchronously growing cell cultures were investigated using a triple
      immunofluorescence staining protocol combined with computerized evaluation of
      staining intensities in individual cells. The simultaneous staining of BrdU,
      cyclin A, and cyclin E made it possible to determine the cell cycle position of
      each cell investigated. Cells at the G(1)/S border were identified on the basis
      of cyclin E content and were further analyzed with respect to cyclin A and BrdU
      content. A method was developed to calculate objective thresholds defining the
      highest staining intensity found in the negative cells in the population. Using
      the thresholds we could distinguish cells with minute amounts of cyclin A and
      BrdU from truly negative cells. We show that the onset of cyclin A accumulation
      and the start of DNA replication occurs at the same time, or deviating by a few
      minutes at the most. We also show that cyclin A accumulates continuously during
      S. This study clearly demonstrates that nuclear cyclin A can be used as a
      reliable marker for the S and G(2) phases in both normal and transformed
      interphase cells.

PMID- 10942582
TI  - CLED: a calcium-linked protein associated with early epithelial differentiation.
AB  - Although it has been well established that Ca(2+) plays a key role in triggering
      keratinocyte differentiation, relatively little is known about the molecules that
      mediate this signaling process. By analyzing a bovine corneal epithelial
      subtraction cDNA library, we have identified a novel gene that we named CLED
      (calcium-linked epithelial differentiation), which encodes a messenger RNA
      present in all stratified squamous epithelia, hair follicle, the bladder
      transitional epithelium, and small intestinal epithelium. The deduced amino acid
      sequence of CLED, based on a bovine partial cDNA and its full-length, human and
      mouse homologues that have been described only as ESTs, contains 2 EF-hand Ca(2+)
      binding domains, a myristoylation motif, and several potential protein kinase
      phosphorylation sites; the CLED protein is therefore related to the S100 protein
      family. In all stratified squamous epithelia, the CLED message is associated with
      the intermediate cell layers. Similar CLED association with cells that are above
      the proliferative compartment but below the terminally differentiated compartment
      is seen in hair follicle, bladder, and small intestinal epithelia. The only
      exception is corneal epithelium, where CLED is expressed in both basal and
      intermediate cells. The presence of CLED in corneal epithelial basal cells, but
      not in the adjacent limbal basal (stem) cells, provides additional, strong
      evidence for the unique lateral heterogeneity of the limbal/corneal epithelium.
      These results suggest that CLED, via Ca(2+)-related mechanisms, may play a role
      in the epithelial cell's commitment to undergo early differentiation, and that
      its down-regulation is required before the cells can undergo the final stages of
      terminal differentiation.

PMID- 10942583
TI  - Accumulation of a form of p27(Kip1) not associated with Cdk-cyclin complexes in
      transforming growth factor-beta-arrested Mv1Lu cells.
AB  - The p27(Kip1) cyclin-dependent kinase inhibitor translocates in response to
      transforming growth factor-beta to a Cdk2-cyclin E complex inhibiting its
      catalytic activity, but the p27(Kip1) protein levels are unaffected [1]. We show
      here that transforming growth factor-beta induces the accumulation of a form of
      p27(Kip1) representing a subpopulation of total p27(Kip1) in growth-arrested
      Mv1Lu epithelial cells. The inducible p27(Kip1) is detectable only by a specific
      p27(Kip1) monoclonal antibody recognizing a native form of p27(Kip1). The
      increase in this subset of p27(Kip1) correlates with G(1) arrest and withdrawal
      of the cells from the cycle induced by transforming growth factor-beta, serum
      starvation, or contact inhibition. In contrast to the majority of p27(Kip1) in
      the cells, the transforming growth factor-beta-inducible p27(Kip1) is devoid of
      cyclin-dependent kinase/cyclin interactions. The results indicate that growth
      arresting treatments induce the accumulation of non-cyclin-dependent kinase-bound
      p27(Kip1), which may function as a reservoir for inhibition of Cdk2-cyclin E
      activities.

PMID- 10942584
TI  - Breakdown of cytoskeletal proteins during meiosis of starfish oocytes and
      proteolysis induced by calpain.
AB  - Meiosis reinitiation in starfish oocytes is characterized by Ca(2+) transients in
      the cytosol and in the nucleus and is accompanied by the disassembly of the
      nuclear envelope, a process which is likely to be mediated by the cleavage of
      selected proteins. We have used mass spectrometry analysis (mass profile
      fingerprinting) on 2D polyacrylamide gels of extracts of oocytes in which meiosis
      resumption was induced by 1-methyladenine and have identified five proteins that
      were specifically degraded: alpha-tubulin, lamin B, dynamin, and two kinds of
      actin. They are all components of the cytoskeleton or associated with it. We then
      investigated whether calpain, which is activated by the increase in cell Ca(2+),
      could cleave the same proteins that became degraded under the influence of 1
      methyladenine and thus be involved in nuclear membrane breakdown. The
      investigation was prompted by the finding that microinjection of calpain into the
      nuclei of prophase arrested oocytes induced meiosis in the absence of 1
      methyladenine. Incubation of prophase arrested (disrupted) oocytes with calpain
      produced a 2D gel protein pattern in which some of the degradation products
      coincided with those seen in oocytes challenged with 1-methyladenine.

PMID- 10942585
TI  - Involvement of EAT/mcl-1, an anti-apoptotic bcl-2-related gene, in murine
      embryogenesis and human development.
AB  - Apoptosis plays an important regulatory role in mammalian embryogenesis and
      development. EAT/mcl-1 (EAT), an anti-apoptotic bcl-2-related gene, was isolated
      during the early differentiation of a human embryonal carcinoma cell line, an
      event which serves as a model of early embryogenesis. EAT is involved in
      apoptotic regulation and is believed to also function as an immediate-early gene.
      Thus it was hypothesized that EAT would be expressed during early embryogenesis
      and would be involved in the regulation of apoptosis during this critical period.
      To clarify this early expression, two antibodies to EAT were generated by use of
      immunizing oligopeptide (aa 37-55) and recombinant protein (aa 31-229) for use in
      immunohistochemistry and immunoblotting, respectively. With these antibodies, we
      then determined EAT expression during murine embryogenesis and in human
      development, using human fetal tissue of 6 to 23 gestational weeks. During murine
      embryogenesis, the EAT protein was found to be rapidly induced after
      fertilization, to peak at the 2-cell stage, to remain constant until the 8-cell
      stage, and then to decrease to below unfertilized egg levels in blastocysts. EAT
      expression patterns in early human development were found to essentially overlap
      those observed in adult tissues which suggest that EAT expression continues until
      adulthood in terminally differentiated tissues. Among tissues distinct to fetal
      development, EAT was detected in the mesonephric (Wolffian) duct and
      paramesonephric (Mullerian) duct. It is also noteworthy that prominent EAT
      immunoreactivity was also observed in large primary oocytes in 21-week fetal
      ovary, but was not detected in primordial germ cells in 23-week fetal testis. In
      summary, EAT expression was detected in hematopoietic, epithelial, neural,
      endocrine, and urogenital cells; this provides evidence that EAT, as an anti
      apoptotic molecule, possibly functions to regulate apoptosis during development
      in these systems.

PMID- 10942586
TI  - Rapid up-regulation of peptide elongation factor EF-1alpha protein levels is an
      immediate early event during oxidative stress-induced apoptosis.
AB  - Hydrogen peroxide (H(2)O(2)) induces apoptosis in cultured cells, in a dose
      dependent manner. Treatment with H(2)O(2) causes decreased mitochondrial
      respiration, along with DNA degradation and the formation of an oligonucleosomal
      ladder, all hallmarks of apoptotic cell death. In this report, we investigate
      alterations in expression of a peptide elongation factor, EF-1alpha, during
      oxidative challenge. EF-1alpha protein levels undergo rapid increase upon
      treatment with H(2)O(2); however, whereas sublethal doses of H(2)O(2) stimulate
      only transient increases of EF-1alpha protein levels, lethal doses produce
      sustained elevation of EF-1alpha levels. Furthermore, pretreatment of H9c2(2-1)
      cells with transcriptional inhibitors fails to abolish the oxidant-induced
      increase in EF-1alpha, and Northern blotting analysis reveals that EF-1alpha mRNA
      levels remain steady throughout the H(2)O(2) treatment period, suggesting that
      the up-regulation of EF-1alpha is mediated posttranscriptionally. Transient
      transfection with an antisense EF-1alpha cDNA protects against hydrogen peroxide
      mediated cytotoxicity in proportion to the degree of repression of EF-1alpha
      protein levels, suggesting that up-regulation of EF-1alpha plays a role in
      expediting the execution of the apoptotic program in response to oxidative
      stress.

PMID- 10942587
TI  - TGF-beta-mediated cell cycle arrest of HPV16-immortalized human ectocervical
      cells correlates with decreased E6/E7 mRNA and increased p53 and p21(WAF-1)
      expression.
AB  - Transforming growth factor beta (TGF-beta) suppresses proliferation and
      potentiates apoptosis of HPV16-immortalized human cervical epithelial cells
      (ECE16-1). Exposure of ECE16-1 to TGF-beta1 increased expression of p53 and
      induced cell cycle arrest. We examined, by Western blotting, expression of p53
      and related cell cycle regulatory proteins after treatment. p53 levels increased
      as a function of time and dose. Increased p53 appeared to be active, since TGF
      beta1 treatment increased the activity of a p53 transcriptional response element
      in a luciferase reporter plasmid. Additionally, the proteins of the p53-regulated
      genes, p21(WAF1), mdm2, and Bax, were increased with similar time and dose
      responses. We did not observe consistent changes in protein levels of cyclin D,
      cyclin E, CDK4, CDK6, CDK2, p27(Kip1), p16(INK4a), or RNA levels of p15(INK4b).
      Activity of CDK4 or 6, measured by phosphorylation of an Rb fragment, remained
      constant during the response period; however, activity of CDK2 (phosphorylation
      of histone H1) decreased. Concordantly, increased levels of p21(WAF1) were
      immunoprecipitated with anti-CDK2 antibodies. During treatment, the
      phosphorylation state of Rb shifted to a hypophosphorylated form. mRNA for the
      HPV E6/E7 genes decreased; however, significant changes in the E7 protein were
      not observed, while increased levels of Rb immunoprecipitated with anti-E7
      antibodies were observed. These data are consistent with the following model. In
      ECE16-1 cells, there exists a fine balance between inhibitory levels of p53 and
      Rb and the antagonists, E6 and E7. TGF-beta1 treatment decreases steady-state
      levels of E6/E7 mRNA, which results in a shifted balance (lowered activity of E6)
      in favor of increased p53 expression, resulting in activation of the cell cycle
      inhibitory gene, p21(WAF1). This protein binds the cyclin E/CDK2 complex that
      maintains Rb in a phosphorylated state. Rb shifts to a hypophosphorylated state,
      resulting in G1 arrest, presumably by binding E2F transcription factors.

PMID- 10942588
TI  - Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to
      monitor the kinetics of cell spreading to artificial surfaces.
AB  - This article describes the optimization of an experimental technique referred to
      as electric cell-substrate impedance sensing (ECIS) to monitor attachment and
      spreading of mammalian cells quantitatively and in real time. The method is based
      on measuring changes in AC impedance of small gold-film electrodes deposited on a
      culture dish and used as growth substrate. Based on experimental data and
      theoretical considerations we demonstrate that high-frequency capacitance
      measurements (f = 40 kHz) are most suited to follow the increasing surface
      coverage of the electrode due to cell spreading. The excellent time resolution of
      the method allowed an in-depth analysis of cell spreading kinetics under various
      experimental conditions. Using ECIS we studied the attachment and spreading of
      epithelial MDCK cells (strain II) on different protein coatings, and investigated
      the influence of divalent cations on spreading kinetics. We quantified the
      inhibitory effect of soluble peptides that mimic the recognition sequence of
      fibronectin and other extracellular matrix proteins (RGDS). We also applied the
      ECIS technique to monitor the detachment of confluent fibroblastic cell layers
      (WI38/VA-13) by means of these peptides.

PMID- 10942589
TI  - The manganese cation disrupts membrane dynamics along the secretory pathway.
AB  - The endoplasmic reticulum and Golgi apparatus play key roles in regulating the
      folding, assembly, and transport of newly synthesized proteins along the
      secretory pathway. We find that the divalent cation manganese disrupts the Golgi
      apparatus and endoplasmic reticulum (ER). The Golgi apparatus is fragmented into
      smaller dispersed structures upon manganese treatment. Golgi residents, such as
      TGN46, beta1,4-galactosyltransferase, giantin, and GM130, are still segregated
      and partitioned correctly into smaller stacked fragments in manganese-treated
      cells. The mesh-like ER network is substantially affected and peripheral ER
      elements are collapsed. These effects are consistent with manganese-mediated
      inhibition of motor proteins that link membrane organelles along the secretory
      pathway to the cytoskeleton. This divalent cation thus represents a new tool for
      studying protein secretion and membrane dynamics along the secretory pathway.

PMID- 10942590
TI  - An integral membrane protein from the nuclear pore complex is also present in the
      annulate lamellae: implications for annulate lamella formation.
AB  - Annulate lamellae (AL) are cytoplasmic arrays of stacked membrane cisternae
      containing densely packed pore complexes which are similar in structure to the
      nuclear pore complexes (NPCs) and thus referred to as annulate lamella pore
      complexes (ALPCs). We have recently shown that the integral nuclear pore membrane
      protein POM121 tagged with green fluorescent protein was correctly targeted to
      the nuclear pores (H. Soderqvist et al., 1997, Eur. J. Biochem. 250, 808-813).
      Here we have investigated if POM121 fused to three tandem molecules of yellow
      fluorescent protein (YFP) (POM121-YFP(3)) also was able to distribute in the
      extensive and well-characterized AL of RC37 and BMGE cells. Transfected RC37 or
      BMGE cells displayed YFP fluorescence around the nuclear envelope, as well as in
      the cytoplasmic AL structures. The YFP fluorescence colocalized perfectly with
      immunostaining using antibodies specific for different NPC proteins. The AL of
      both transfected and untransfected BMGE cells resisted extractions with Tx-100
      and 250 mM NaCl, but were completely solubilized at 450 mM NaCl. Loss of YFP
      fluorescence and immunostaining for other NPC proteins correlated under all
      extraction conditions tested, suggesting that overexpressed POM121-YFP(3) had
      become an integrated part both of the NPCs and of the ALPCs. Furthermore, we have
      generated a stable BHK cell line expressing POM121-YFP(3) located exclusively at
      the nuclear pores. Treatment with vinblastine sulfate, which induces formation of
      AL in a variety of cells, resulted in distribution of POM121-YFP(3) into
      cytoplasmic foci colocalizing with immunostaining for peripheral NPC proteins.
      Taken together, the results show that YFP-tagged POM121 is able to distribute in
      drug-induced or naturally occurring AL, suggesting that POM121 is a natural
      constituent of ALPCs. In COS cells, which normally lack or have very little AL,
      YFP-tagged POM121 distributed in the nuclear pores when expressed at low levels.
      However, at high expression levels the YFP fluorescence also distributed in a
      number of brightly fluorescing cytoplasmic dots or foci, which were not present
      in untransfected cells. This was also true for untagged POM121. The cytoplasmic
      foci varied in size from 0. 1 to 2 microm and were distinctly located in the
      immediate vicinity of ER cisternae (without colocalizing) and also contained
      other nuclear pore proteins, indicating that they may represent cytoplasmic AL.
      This idea is supported by time-lapse studies of postmitotic assembly of these
      structures. This raises the question of the role of POM121 in ALPC and NPC
      biogenesis.

PMID- 10942591
TI  - Altered response of a human squamous cell carcinoma cell line to 1, 25
      dihydroxyvitamin D(3) after transfer of a normal chromosome 11.
AB  - Previous work in our laboratory using functional assays for tumorigenicity
      identified a tumor suppressor element on human chromosome 11q for the cutaneous
      squamous cell carcinoma cell line A388.6TG.c2. In this report, we screened a
      variety of agents for differential effects on A388.6TG.c2 compared to a growth
      suppressed chromosome 11 microcell hybrid of A388.6TG.c2. One of the agents, 1,
      25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3); calcitriol), exerted a growth-altering
      effect on A388.6TG.c2, which formed rounded cell clusters across the surface of
      the raft by Day 6 of treatment. In contrast, full-length chromosome 11 hybrids of
      A388.6TG.c2, as well as two other squamous cell carcinoma cell lines (FaDu and
      A431), when treated with 1,25(OH)(2)D(3), failed to demonstrate this cell
      clumping phenotype. To pursue the hypothesis that the growth suppressor element
      is involved in altering the response to 1, 25(OH)(2)D(3), we tested microcell
      hybrids carrying t(X;11) chromosomes lacking large portions of 11q. Although
      these hybrids, like the parent A388.6TG.c2 cells, demonstrated extensive growth
      in organotypic cultures, they failed to form cell clusters with 1, 25(OH)(2)D(3)
      treatment. These results suggest that the chromosome 11 element that alters the
      response to 1,25(OH)(2)D(3) is distinct from the growth-suppressing element. An
      examination of differentiation marker expression revealed identical patterns of
      basal and suprabasal markers for A388.6TG.c2 and for a chromosome 11 hybrid with
      or without treatment with 1,25(OH)(2)D(3). Finally, characterization of candidate
      tumor suppressor gene PPP2R1B, which encodes for a subunit of protein phosphatase
      2A (PP2A), showed seemingly insignificant alterations by cDNA sequence analysis.
      Collectively, the data suggest that human chromosome 11 contains two different
      tumor suppressor elements that may account for the two areas of loss of
      heterozygosity observed on the long arm of this chromosome.

PMID- 10942592
TI  - Cell types required to efficiently innervate human muscle cells in vitro.
AB  - Previous studies carried out in our laboratory have shown that myofibers formed
      by fusion of muscle satellite cells from donors with spinal muscular atrophy
      (SMA) type I or II undergo a characteristic degeneration 1.5-3 weeks after
      innervation with rat embryonic spinal cord explants. The only cells responsible
      for degeneration of innervated cocultures are SMA muscle satellite cells. In
      order to study the kinetics of nerve and muscle cell degeneration in nerve-muscle
      cocultures implicating SMA muscle cells, we attempted to simplify the nervous
      component of the coculture and identify the nerve cell types necessary for a
      successful innervation. We demonstrate here that motoneurons alone were unable to
      innervate myotubes. However, when three cell types (motoneurons, sensory neurons,
      and Schwann cells) were added onto a reconstituted muscular component consisting
      of cloned muscle satellite cells and cloned muscular fibroblasts, myotubes
      contracted, indicating that functional neuromuscular junctions were formed. We
      concluded that the three cell types were required for a successful innervation.
      Moreover, we studied the effects of culture medium conditioned by different
      combinations of nerve cells on innervation; we observed that physical contacts
      among sensory neurons, motoneurons, and myotubes are required for a successful
      innervation; in contrast Schwann cells can be replaced by a Schwann-cell
      conditioned medium, indicating that these cells produce a putative soluble
      "innervation-promoting factor." Obviously such a reconstituted system does not
      reflect the in vivo situation but it allows the formation of functional motor
      synapses and could therefore allow us to elucidate neuromuscular disease
      pathogenesis, especially that of spinal muscular atrophy.

PMID- 10942593
TI  - Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis
      genes in systemic sclerosis.
AB  - We have used representational difference analysis (RDA) to identify up-regulated
      genes in skin fibroblasts from fibrotic lesions obtained from patients with
      systemic sclerosis (scleroderma). RDA of cDNA libraries derived from fibroblasts
      from involved and uninvolved skin detected several differentially expressed
      genes. One such gene consistently up-regulated in scleroderma cells coded for
      human connective tissue growth factor (CTGF). Other studies described here show
      that the CTGF protein is readily detected in cultures of systemic sclerosis
      fibroblasts but was not detected in comparable normal cells. High levels of CTGF
      are also evident in biological fluids from patients with systemic sclerosis.
      TGFbeta stimulates CTGF production in both normal and systemic sclerosis
      fibroblasts with the latter found to be higher producers. Moreover, an analysis
      of constitutive and TGFbeta-induced CTGF gene activation showed altered and
      elevated transcriptional responses in systemic sclerosis cells compared with
      controls. CTGF stimulated a two- to threefold increase in proalpha1(I) collagen
      and fibronectin synthesis by both dermal and lung fibroblasts in culture and
      promoted significant matrix remodeling of fibroblast-populated three-dimensional
      collagen lattices. A direct relation between the overexpression of CTGF and
      elevated collagen synthesis was suggested by the observation that transfection of
      a CMV-CTGF cDNA construct and protein expression in fibroblasts increased the
      transcription of a Col 1alpha2 promoter-reporter construct to levels seen in
      systemic sclerosis fibroblasts. Using Col 1alpha2 promoter deletion constructs
      the CTGF responsive element was localized to the first 379 bp upstream of the
      transcriptional start site. These data indicate that there is an overexpression
      of CTGF in the systemic sclerosis cells, probably due to increased gene
      transcription, and suggest that the dysregulation of CTGF production is an
      important factor in fibroblast activation and the excessive deposition of
      collagen in systemic sclerosis.

PMID- 10942594
TI  - Specific inhibition of rRNA transcription and dynamic relocation of fibrillarin
      induced by mercury.
AB  - Current evidence suggests that the nucleolus is composed of different
      substructures that are dynamic and form in response to the requirement for new
      ribosome synthesis. Thus, agents that disrupt nucleolar organization may
      deregulate basic cellular events and eventually contribute to human disease. Here
      we report that environmentally relevant concentrations (5 microM) of inorganic
      mercury induce a redistribution of nucleolar protein fibrillarin from the
      nucleolus to the nucleoplasm in epithelial cell lines. Since treatment with
      transcription inhibitors led to a similar relocation of fibrillarin, the effects
      of mercury on transcription were studied by run-on transcription assays: mercuric
      ions specifically blocked synthesis of ribosomal RNA, whereas activity of RNA
      polymerase II remained unchanged and occurred throughout the nucleoplasm.
      Moreover, we show by double-labeling that inhibition of nucleolar transcription
      and redistribution of fibrillarin occur simultaneously, underlining that
      fibrillarin relocation is a consequence of the blockade of ribosomal RNA
      synthesis by mercury. We also detected redistribution of fibrillarin in vivo,
      e.g., in splenic cells of mice chronically exposed to HgCl(2). Thus, implications
      of this alteration of nuclear structure and function for mercury-induced
      autoimmunity are discussed.

PMID- 10942595
TI  - A visual intracellular classification strategy for uncharacterized human
      proteins.
AB  - The human cDNA and genomic sequencing projects will result in the identification
      and isolation of some 140,000 genes, the majority of which lack predicted
      functions and for which the cellular localizations are not known. The
      identification and characterization of protein components of specific cell
      structures and machineries are essential steps not only toward defining functions
      of genes but also toward understanding cell function and regulation. We describe
      here a new approach, termed PROLOC, which uses full-length cDNAs for systematic
      classification of novel proteins as a functional pointer. We have PCR-amplified
      25 uncharacterized human genes and expressed the encoded proteins as GFP fusions
      in a human cell line. This pilot project has identified novel proteins associated
      with the nucleolus, mitochondria, the ER, the ER-Golgi-intermediate compartment
      (ERGIC), the GC, the plasma membrane, and cytoplasmic foci. This visual
      classification approach may be scaled up to handle a large number of novel genes
      and permit the generation of a global cellular protein localization map. Such
      information should be valuable for many aspects of functional genomics and cell
      biology.

PMID- 10942596
TI  - Determinants of NPC1 expression and action: key promoter regions,
      posttranscriptional control, and the importance of a "cysteine-rich" loop.
AB  - Mutations in the NPC1 gene cause Niemann-Pick type C disease, which is
      characterized by the accumulation of free cholesterol and other lipids in
      lysosomes. The NPC1 glycoprotein is located in a late endosomal compartment that
      transiently interacts with lysosomes. To identify factors regulating NPC1
      expression and action, we analyzed the function of the human NPC1 promoter in
      human-derived ovarian, hepatic, and neuronal cells. A fragment containing the
      first 208 base pairs upstream from the major transcription initiation site was
      sufficient to drive near maximal NPC1 promoter activity. Deletion analysis
      revealed that sequences between base pairs -111 and -37 play an important role in
      controlling NPC1 transcription. Treatment of proliferating granulosa cells with
      30 microM progesterone, which induces a reversible phenocopy of the cholesterol
      trafficking defect of Niemann-Pick type C disease, increased NPC1 mRNA levels
      threefold. The protein synthesis inhibitor, cycloheximide, also increased NPC1
      mRNA levels, augmenting the progesterone-induced increase in NPC1 mRNA abundance.
      Progesterone treatment was shown to increase the mRNA half-life, but did not
      affect NPC1 promoter activity. Cysteine residues in a "cysteine-rich" loop
      predicted to reside in the intralumenal compartment of vesicles containing NPC1
      were mutated, resulting in proteins that were incapable of correcting the
      cholesterol trafficking defect in CT60 cells, a Chinese hamster cell line in
      which the endogenous NPC1 gene is inactivated. Converting isoleucine 1061, also
      predicted to lie within the cysteine-rich loop, to a threonine residue
      inactivated the protein as well. The I1061T mutation is one of the most common
      mutations in Niemann-Pick type C disease. All of the cysteine-rich loop mutants
      were localized to cholesterol-engorged lysosomes in a pattern mimicking the
      distribution of NPC1 in progesterone-treated cells. A recombinant protein
      representing the cysteine-rich loop was shown to bind to a zinc-NTA agarose
      column. We conclude: (1) that cis elements residing in the first 111 base pairs
      upstream from the transcription start site are critical for transcription of the
      NPC1 gene; (2) that NPC1 expression is subject to posttranscriptional regulation
      in response to treatments that disrupt NPC1 function; and (3) that an
      intralumenal cysteine-rich loop with zinc-binding activity is critical to NPC1's
      ability to unload lysosomal cargo.

PMID- 10942598
TI  - Induction of ribosomal subunits misassembly by antisense RNAs to control cell
      growth.
AB  - The assembly of ribosomal subunits starting from free ribosomal RNA and protein
      of Dictyostelium discoideum was induced in vitro in the presence of several
      oligoribonucleotides complementary to defined sequences of ribosomal RNA. The
      reconstituted particles had a full complement of ribosomal proteins, but did not
      function in an in vitro protein synthesis system and were disassembled following
      interaction with mRNA. The same result was obtained in vivo by fusing the
      oligodeossiribonucleotides coding for the selected oligoribonucleotides to the
      promoter of the gene coding for contact site A protein. This gene is expressed
      only in the first part of development. Transfected growing cells, transferred in
      developing buffer in the presence of pulses of cAMP, accumulated significant
      amounts of the oligoribonucleotides. When retransferred to the growth medium,
      they grew progressively more slowly, until their doubling time doubled,
      apparently due to the availability of a limiting amount of functional ribosomes.
      To avoid disassembly of misassembled subunits (G. Mangiarotti et al., 1997, J.
      Biol. Chem. 272, 27818-27822), two oligoribonucleotides complementary to
      sequences present at the 5' ends of pre-17S and pre-26S RNAs were also induced to
      accumulate during early development with the same technique. When transfected
      cells were retransferred to the growth medium, their rate of growth declined
      rapidly to zero and cells died, apparently because they were unable to
      disassemble misassembled ribosomal subunits and avoid their entry into
      polyribosomes. This technique to perturb protein synthesis, arrest cell growth,
      and cause cell suicide will be tested in abnormally growing animal cells.

PMID- 10942597
TI  - Rab11b is essential for recycling of transferrin to the plasma membrane.
AB  - Members of the Rab family of small GTPases play important roles in membrane
      trafficking along the exocytic and endocytic pathways. The Rab11 subfamily
      consists of two highly conserved members, Rab11a and Rab11b. Rab11a has been
      localized both to the pericentriolar recycling endosome and to the trans-Golgi
      network and functions in recycling of transferrin. However, the localization and
      function of Rab11b are completely unknown. In this study green fluorescent
      protein (GFP)-tagged Rab11b was used to determine its subcellular localization.
      GFP-Rab11b colocalized with internalized transferrin, and using different mutants
      of Rab11b, the role of this protein in transferrin uptake and recycling was
      examined. Two of these mutants, Rab11b-Q/L (constitutively active) and Rab11b-S/N
      (constitutively inactive), strongly inhibited the recycling of transferrin.
      Interestingly, both of them had no effect on transferrin uptake. In contrast, the
      C-terminally altered mutant Rab11b-DeltaC, which cannot be prenylated and
      therefore cannot interact with membranes, did not interfere with wild-type Rab11b
      function. From these data we concluded that functional Rab11b is essential for
      the transport of internalized transferrin from the recycling compartment to the
      plasma membrane.

PMID- 10942599
TI  - Molecular cloning and analysis of a group of genes differentially expressed in
      cells which overexpress the Hoxa-1 homeobox gene.
AB  - The homeobox gene Hoxa-1 is transcriptionally regulated by retinoic acid (RA) and
      encodes a transcription factor which has been shown to play important roles in
      cell differentiation and embryogenesis. In order to clone and characterize target
      genes of Hoxa-1, we utilized differential hybridization screening and cDNA
      subtractive hybridization methods to identify genes which are differentially
      expressed in F9-10, a murine F9 teratocarcinoma stem cell line which expresses
      high levels of exogenous Hoxa-1, compared to F9 wild-type stem cells, which do
      not express endogenous Hoxa-1 mRNA in the absence of RA. Twenty-eight candidate
      genes were identified; these genes encode very diverse proteins, including
      signaling molecules such as BMP-4, the enzyme superoxide dismutase, the cell
      adhesion molecule cadherin-6, proteins involved in gene transcription such as HMG
      1 and SAP18, homeodomain-containing proteins Gbx-2 and Evx-2, and cell cycle
      regulatory proteins such as the retinoblastoma binding protein-2. Clone 104
      encodes a novel protein; the expression of the clone 104 mRNA is also regulated
      in a fashion very similar to that of the exogenous Hoxa-1 gene in another F9 cell
      line, called F9-tet-Hoxa1-8, in which the exogenous Hoxa-1 mRNA expression is
      tightly regulated by a Tet-off gene expression system. These data strongly
      suggest that clone 104 is a direct downstream target of the transcription factor
      Hoxa-1. The cDNA sequence of clone 104 is related to that of human ubiquitin
      carboxyl-terminal hydrolase T. Further characterization of these putative Hoxa-1
      target genes will aid in delineating the functions of the Hoxa-1 protein in the
      differentiation processes which occur during embryogenesis.

PMID- 10942600
TI  - Mitogen-independent phosphorylation of S6K1 and decreased ribosomal S6
      phosphorylation in senescent human fibroblasts.
AB  - The p70 ribosomal S6 kinase (S6K1) is rapidly activated following growth factor
      stimulation of quiescent fibroblasts and inhibition of this enzyme results in a
      G(1) arrest. Phosphorylation of the ribosomal S6 protein by S6K1 regulates the
      translation of both ribosomal proteins and initiation factors, leading to an
      increase in protein synthesis. We have examined the activation of S6K1 in human
      fibroblasts following mitogen stimulation. In early passage fibroblasts S6K1 is
      activated following serum stimulation as evidenced by increased kinase activity
      and site-specific phosphorylation. In contrast, site-specific phosphorylation of
      S6K1 at Thr421/Ser424 is diminished in senescent fibroblast cultures. A second
      phosphorylation site within S6K1 (Ser411) is phosphorylated even in the absence
      of serum stimulation and the enzyme shows increased phosphorylation as judged by
      decreased electrophoretic mobility. Inhibitor studies indicate that this
      phosphorylation is dependent upon the mammalian target of rapamycin, PI 3-kinase,
      and the MAPK pathway. In order to understand the consequences of the altered
      phosphorylation of the S6K1, we examined the phosphorylation state of the
      ribosomal S6 protein. In early passage fibroblasts the ribosomal S6 protein is
      phosphorylated upon serum stimulation while the phosphorylation of the ribosomal
      S6 protein is drastically reduced in senescent fibroblasts. These results suggest
      that the intracellular regulators of S6K1 are altered during replicative
      senescence leading to a deregulation of the enzyme and a loss of ribosomal S6
      phosphorylation.

PMID- 10942601
TI  - Epidermal growth factor receptor signaling activates met in human anaplastic
      thyroid carcinoma cells.
AB  - Overexpression of Met is a common finding in thyroid carcinomas. Recently, we
      reported on overexpression and ligand-independent constitutive activation of Met
      in anaplastic thyroid carcinoma cells. In the present study we have investigated
      a putative mechanism for this phenomenon. Cell lines with constitutively
      activated Met expressed both TGF-alpha mRNA and protein. Western blot analysis
      revealed expression of receptors for epidermal growth factor (EGFR) in all
      carcinoma cell lines; in tumor cells with elevated levels of TGF-alpha mRNA there
      was a constitutive tyrosine phosphorylation of the EGFRs. Preincubation of
      carcinoma cells with suramin decreased EGFR activation and downregulated Met
      expression as well as the ligand-independent phosphorylation of Met. Similar
      results were obtained with a EGFR tyrosine kinase inhibitor, AG 1478. The MEK
      inhibitor U0126 had an even more pronounced effect compared to AG 1478,
      indicating a Ras/MAPK-mediated signal in the regulation of Met expression and
      activation. Inhibition of EGFR signaling also decreased proliferation of the
      anaplastic thyroid carcinoma cells. Thus, aberrant activation of EGFRs may lead
      to an overexpression and activation of Met, which may be of importance for the
      malignant phenotype of anaplastic thyroid carcinomas.

PMID- 10942602
TI  - Cyclin E-cdk2 phosphorylation promotes late G1-phase degradation of MyoD in
      muscle cells.
AB  - Proliferating myoblasts already express MyoD before the induction of
      differentiation. Overexpression of MyoD in normal and transformed cell lines was
      shown to block cells from entering S phase, suggesting that the MyoD growth
      suppressive effect must be tightly controlled in growing myoblasts. Here we show
      that during G1 phase, but not in G2, MyoD abundance is down-regulated by the
      ubiquitin-proteasome pathway through phosphorylation of serine 200. Roscovitine,
      a specific inhibitor of cyclin-Cdk2 complexes, prevents both phosphorylation and
      degradation of MyoD in G1. Inhibition of the ubiquitin-dependent proteasome
      pathway by MG132 results in stabilization of MyoD-wt, with little effect on a
      MyoD mutant where serine 200 is replaced by an alanine. Our results show that
      MyoD Ser200 is the substrate for phosphorylation by cyclin E-Cdk2 stimulating its
      degradation by the ubiquitin-proteasome system which controls MyoD levels in G1.
      Phosphorylation/degradation of MyoD at the end of G1 thus represents the
      regulatory checkpoint in growing myoblasts allowing progression into S phase in a
      manner similar to the recently examplified cdk2-phosphorylation/degradation of
      p27(Kip1).

PMID- 10942603
TI  - Activation of caspases measured in situ by binding of fluorochrome-labeled
      inhibitors of caspases (FLICA): correlation with DNA fragmentation.
AB  - Activation of caspases is the key event of apoptosis and new methods are needed
      to assay this event, particularly in situ, in individual cells. To measure in
      situ caspases activation in the present study we employed fam-VAD-fmk and fam
      VEID-fmk, the fluorochrome (fam)-labeled inhibitors of caspases (FLICA), which
      through the fluoromethylketone (fmk) moiety bind to active center of the
      activated enzymes. The peptide moiety of these inhibitors defines their
      specificity; VAD is generic to most caspases and VEID is caspase-6 specific. The
      frequencies of cells showing caspases activation were compared with those showing
      DNA fragmentation (detected by the TUNEL assay) in the same cultures. Apoptosis
      of HL-60 cells was induced by DNA topoisomerase I inhibitor camptothecin (CPT) or
      tumor necrosis factor-alpha combined with cycloheximide (TNF-alpha + CHX). The
      cells that bound FLICA had morphological changes typical of apoptosis. The
      intensity of their fluorescence was measured by laser scanning cytometry. Maximal
      rate of activation of the caspases, measured by the increase in frequency of the
      cells that bound fam-VAD-fmk, occurred between 30 and 90 min after the
      administration of TNF-alpha + CHX and between 2 and 4 h after the administration
      of CPT. In the CPT-treated cultures about 30% fewer cells bound fam-VEID-fmk than
      fam-VAD-fmk which suggests that the activation of caspase-6 was delayed or was
      not induced in some cells. A strong overall correlation between the cytometric
      assays of the apoptotic index based on the detection of caspases activation by
      the FLICA and the TUNEL assay was observed. The data indicate that FLICA offers a
      rapid and convenient method of assessing caspase's activation in individual cells
      and can also be used to estimate the frequency of apoptosis.

PMID- 10942604
TI  - Increasing fidelity in parsimony analysis of dorid nudibranchs by differential
      weighting, or a tale of two genes.
AB  - Phylogenetic analyses of 22 dorid nudibranch species and 2 outgroup
      (dendronotacean and notaspidean) species were performed using sequences from two
      different mitochondrial genes (16S rRNA and COI). Several methods of differential
      weighting (positional, transformational, and combined) were explored using
      character congruence between the linked data sets as an optimality criterion.
      Most weighting schemes gave an increase in congruence as well as phylogenetic
      signal. The optimal weighting scheme according to the criterion was successive
      weighting of each character (positional weighting) with 1/(number of steps) in
      combination with LN weighting of character changes (transformational weighting).
      The cladogram from the optimal weighting scheme was, in general, congruent with
      existing classifications. One exception is the genus Goniodoris, which was
      paraphyletic if Okenia aspersa was not also included.

PMID- 10942605
TI  - A rapid heuristic algorithm for finding minimum evolution trees.
AB  - The minimum sum of branch lengths (S), or the minimum evolution (ME) principle,
      has been shown to be a good optimization criterion in phylogenetic inference.
      Unfortunately, the number of topologies to be analyzed is computationally
      prohibitive when a large number of taxa are involved. Therefore, simplified,
      heuristic methods, such as the neighbor-joining (NJ) method, are usually employed
      instead. The NJ method analyzes only a small number of trees (compared with the
      size of the entire search space); so, the tree obtained may not be the ME tree
      (for which the S value is minimum over the entire search space). Different
      compromises between very restrictive and exhaustive search spaces have been
      proposed recently. In particular, the "stepwise algorithm" (SA) utilizes what is
      known in computer science as the "beam search," whereas the NJ method employs a
      "greedy search." SA is virtually guaranteed to find the ME trees while being much
      faster than exhaustive search algorithms. In this study we propose an even faster
      method for finding the ME tree. The new algorithm adjusts its search
      exhaustiveness (from greedy to complete) according to the statistical reliability
      of the tree node being reconstructed. It is also virtually guaranteed to find the
      ME tree. The performances and computational efficiencies of ME, SA, NJ, and our
      new method were compared in extensive simulation studies. The new algorithm was
      found to perform practically as well as the SA (and, therefore, ME) methods and
      slightly better than the NJ method. For searching for the globally optimal ME
      tree, the new algorithm is significantly faster than existing ones, thus making
      it relatively practical for obtaining all trees with an S value equal to or
      smaller than that of the NJ tree, even when a large number of taxa is involved.

PMID- 10942606
TI  - Testing morphological concepts of orders of pleurocarpous mosses (Bryophyta)
      using phylogenetic reconstructions based on TRNL-TRNF and RPS4 sequences.
AB  - The ordinal classification of pleurocarpous mosses rests on characters such as
      branching mode and architecture of the peristome teeth that line the mouth of the
      capsule. The Leucodontales comprise mainly epiphytic taxa, characterized by
      sympodial branching and reduced peristomes, whereas the Hypnales are primarily
      terricolous and monopodially branching. The third order, the Hookeriales, is
      defined by a unique architecture of the endostome. We sampled 78 exemplar taxa
      representing most families of these orders and sequenced two chloroplast loci,
      the trnL-trnF region and the rps4 gene, to test the monophyly and relationships
      of these orders of pleurocarpous mosses. Estimates of levels of saturation
      suggest that the trnL-trnF spacer and the third codon position of the rps4 gene
      have reached saturation, in at least the transitions. Analyses of the combined
      data set were performed under three optimality criteria with different sets of
      assumptions, such as excluding hypervariable positions, downweighting the most
      likely transformations, and indirect weighting of rps4 codon positions by
      including amino acid translations. Multiple parallelism in nonsynonymous
      mutations led to little or no improvement in various indices upon inclusion of
      amino acid sequences. Trees obtained under likelihood were significantly better
      under likelihood than the trees derived from the same matrix under parsimony. Our
      phylogenetic analyses suggest that (1) the pleurocarpous mosses, with the
      exception of the Cyrtopodaceae, form a monophyletic group which is here given
      formal recognition as the Hypnidae; (2) the Leucodontales are at least
      paraphyletic; and (3) the Hypnales form, with most members of the Leucodontalean
      grade, a monophyletic group sister to a Hookerialean lineage. The
      Hypopterygiaceae, Hookeriales, and a clade composed of Neorutenbergia,
      Pseudocryphaea, and Trachyloma likely represent a basal clade or grade within the
      Hypnidae. These results suggest that mode of branching and reduced peristomes are
      homoplastic at the ordinal level in pleurocarpous mosses.

PMID- 10942607
TI  - A phylogeny of the trimeresurus group of pit vipers: new evidence from a
      mitochondrial gene tree.
AB  - The Trimeresurus group is an important radiation of over 40 Asian pit viper
      species. Once considered congeneric, four genera are generally currently
      recognized (Trimeresurus sensu stricto, Ovophis, Protobothrops, and
      Tropidolaemus) but relationships within and between these are still unclear. This
      study, based on mitochondrial cytochrome b sequences, is the first to include a
      large number of species (21) and demonstrates that the current taxonomy does not
      adequately represent either the relationships or the genetic diversity present in
      the complex. Although many deeper nodes are not strongly supported, the following
      novel conclusions are all well supported: (1) the paraphyly of Trimeresurus sensu
      stricto, (2) the presence of several divergent clades within Trimeresurus sensu
      stricto, (3) the paraphyly of some widespread, medically significant, species,
      (4) the nonmonophyly of Ovophis, and (5) the monophyly of Protobothrops. Mapping
      of morphological characters onto the mitochondrial tree further supports the four
      groups proposed for Trimeresurus sensu stricto.

PMID- 10942608
TI  - Phylogeny of the syrphoidea (Diptera) inferred from mtDNA sequences and
      morphology with particular reference to classification of the pipunculidae
      (Diptera).
AB  - Sequence data from 420 bp of mitochondrial 12s ribosomal DNA and 490 bp of 16s
      rDNA were analyzed for 27 species of Syrphoidea (Diptera) and two outgroup taxa.
      Morphological data for the Pipunculidae were combined with the pipunculid
      molecular data set. A partition homogeneity test on these data sets revealed no
      significant incongruence. The pipunculid phylogeny from molecular data closely
      resembles the published phylogeny based on morphology, with differences only with
      respect to the Nephrocerinae. There is very strong support for the monophyly of
      the Pipunculinae and the Chalarinae. The Nephrocerinae are hypothesized to be
      paraphyletic. Within the Syrphidae, there is support for a monophyletic Syrphinae
      and Microdontinae, but the Eristalinae are paraphyletic. More data are needed to
      resolve the eristaline phylogeny.

PMID- 10942609
TI  - Phylogenetic relationships, morphological incongruence, and geographic speciation
      in the fontinalaceae (Bryophyta).
AB  - Nuclear ribosomal DNA (internal transcribed spacer region) and chloroplast DNA
      (trnL-trnF region) were sequenced from 40 samples representing all three genera
      (Brachelyma, Dichelyma, and Fontinalis) and 18 species of the aquatic moss
      family, Fontinalaceae. Phylogenetic reconstructions recovered from separate and
      combined analyses were used to test the hypotheses that Fontinalis and Dichelyma
      are monophyletic (Brachelyma is monotypic), that groups of species within
      Fontinalis based on leaf morphology (keeled, concave, plane) form monophyletic
      groups, and that species delineation based on morphological characters within
      Fontinalis are congruent with nr- and cpDNA gene trees. Using Brachelyma subulata
      to root the tree, both Dichelyma and Fontinalis are monophyletic and
      patristically divergent (each united by >15 synapomorphic mutations). Groups of
      species within Fontinalis defined by leaf morphology are polyphyletic and it is
      clear that leaf morphology is labile in the genus. As defined morphologically,
      species of Fontinalis are nonmonophyletic for both nr- and cpDNA sequences and
      populations of some morphological taxa are separated in widely divergent clades.
      Molecular evidence suggests that at least some morphospecies are artificial,
      defined by convergent leaf forms. The weight of the evidence indicates that F.
      antipyretica is positively paraphyletic, with European populations more closely
      related to (i.e., share a more recent common ancestor with) European endemic
      species than to North American populations that are morphologically conspecific.
      North American populations are more closely related to North American endemic
      species.

PMID- 10942610
TI  - The evolution of the atpbeta-rbcL intergenic spacer in the epacrids (Ericales)
      and its systematic and evolutionary implications.
AB  - Sequence data from the noncoding region separating the plastid genes atpbeta and
      rbcL were gathered for 27 epacrid taxa, representing all previously recognized
      infrafamilial groups, and four outgroup taxa (Ericaceae), to address several
      persistent phylogenetic questions in the group. Parsimony analyses were conducted
      on these data, as well as on a complementary rbcL sequence dataset assembled from
      the literature and the combined dataset. The atpbeta-rbcL spacer was notable for
      the high frequency of insertion-deletion mutations (indels); their distributions
      were coded as binary characters and included as a adjunct matrix in some of the
      analyses. The phylogenetic patterns derived from the spacer and rbcL data and the
      combined analyses, both including and excluding the indel data, concur in
      resolving seven major lineages corresponding to the tribes of Crayn et al. (1998,
      Aust. J. Bot. 46, 187-200), viz. Prionoteae, Archerieae, Oligarrheneae,
      Cosmelieae, Richeeae, Epacrideae, and Styphelieae. The relationships of the
      tribes and within Styphelieae, however, are not convincingly resolved. Minor
      conflicts in the positions of some taxa between the spacer and the rbcL trees are
      poorly supported. Among epacrids, the spacer region provided more cladistically
      informative characters than rbcL and resulted in trees with lower homoplasy.
      Further, the spacer data, when analyzed alone and when combined with rbcL,
      resolved several clades that could not be retrieved on rbcL data alone and
      provided increased support for many other relationships. The evolution of a
      putative three-base inversion associated with a hairpin secondary structure in
      the spacer region is discussed in the light of the inferred phylogeny.

PMID- 10942611
TI  - Molecular phylogeny of parasitic zygomycota (Dimargaritales, zoopagales) based on
      nuclear small subunit ribosomal DNA sequences.
AB  - We analyzed sequence data of the 18S rDNA gene from representatives of nine
      mycoparasitic or zooparasitic genera to infer the phylogenetic relationships of
      these fungi within the Zygomycota. Phylogenetic analyses identified a novel
      monophyletic clade consisting of the Zoopagales, Kickxellales, Spiromyces, and
      Harpellales. Analyses also identified a monophyletic mycoparasitic-zooparasitic
      Zoopagales clade in which Syncephalis, Thamnocephalis, and Rhopalomyces form a
      sister group to a Piptocephalis-Kuzuhaea clade. Although monophyly of the
      mycoparasitic Dimargaritales received strong bootstrap and decay index support,
      phylogenetic relationships of this order could not be resolved because of the
      unusually high rate of base substitutions within the 18S rDNA gene. Overall, the
      18S gene tree topology is weak, as reflected by low bootstrap and decay index
      support for virtually all internal nodes uniting ordinal and superordinal taxa.
      Nevertheless, the 18S rDNA phylogeny is mostly consistent with traditional
      phenotypic-based classification schemes of the Fungi.

PMID- 10942612
TI  - Mitochondrial phylogeny of extant Hawaiian tree snails (Achatinellinae).
AB  - Hawaiian tree snails in the endemic subfamily Achatinellinae display a staggering
      variety of shell colors and banding patterns. Despite numerous attempts to
      classify this morphological variation, a conclusive phylogeny has not been
      proposed. To improve conservation efforts, we sought to better understand the
      species identities and phylogenetic relationships among the extant species of
      Achatinella and Partulina using partial mitochondrial 16S ribosomal DNA
      sequences. The reconstructed phylogeny showed a high degree of support for more
      recent branches, but gave little support to deeper nodes. The most confident
      branches challenge previous systematic arrangements of these snails, grouping
      species that previously had been placed into different subgenera. High levels of
      sequence divergence within some species may reflect the long-term isolation of
      subpopulations. Rapid rates of sequence divergence may have saturated base
      substitutions and contributed to the lack of resolution of higher-order
      relationships. We did not find support for the monophyly of the Achatinella
      species, nor thus for a single colonization of Oahu from Maui Nui.

PMID- 10942613
TI  - Molecular phylogenetic position of Japanese Abies (Pinaceae) based on chloroplast
      DNA sequences.
AB  - The phylogenetic positions of Japanese Abies species (A. firma, A. homolepis, A.
      veitchii, A. sachalinensis, and A. mariesii) were revealed based on nucleotide
      sequences of chloroplast DNA. First, rbcL sequences of 24 Abies species worldwide
      were analyzed to clarify the phylogenetic position of the Japanese Abies within
      this genus. While 4 of the Japanese species formed a monophyletic group with
      almost no sequence divergence, A. mariesii was placed into a clearly different
      group with North American species. Second, to clarify the relationships among the
      species in the monophyletic group, sequences of rbcL, matK, and six spacer
      regions (total ca. 5 kb) were analyzed for 12 species of the group, with A.
      mariesii as an outgroup. Although a unique sequence and some species-specific
      sequences were detected in A. mariesii and in A. firma and A. homolepis,
      respectively, A. veitchii and A. sachalinensis gave identical sequences for all
      the sequenced regions.

PMID- 10942615
TI  - Utility of the mitochondrial cytochrome oxidase II gene for resolving
      relationships among black flies (Diptera: simuliidae).
AB  - The complete mitochondrial cytochrome oxidase II gene was sequenced from 17 black
      flies, representing 13 putative species, and used to infer phylogenetic
      relationships. A midge (Paratanytarsus sp.) and three mosquitoes (Aedes aegypti,
      Anopheles quadrimaculatus, and Culex quinquefasciatus) were used as outgroup
      taxa. All outgroup taxa were highly divergent from black flies. Phylogenetic
      trees based on weighted parsimony (a priori and a posteriori), maximum
      likelihood, and neighbor-joining (log-determinant distances) differed
      topologically, with deeper nodes being the least well-supported. All analyses
      supported current classification into species groups but relationships among
      those groups were poorly resolved. The majority of phylogenetic signal came from
      closely related sister taxa. The CO-II gene may be useful for exploring
      relationships at or below the subgeneric level, but is of questionable value at
      higher taxonomic levels. The weighting method employed gave phylogenetic results
      similar to those reported by other authors for other insect CO-II data sets. A
      best estimate of phylogenetic relationships based on the CO-II gene is presented
      and discussed in relation to current black fly classification.

PMID- 10942614
TI  - Molecular phylogenetic relationships of pond frogs distributed in the Palearctic
      region inferred from DNA sequences of mitochondrial 12S ribosomal RNA and
      cytochrome b genes.
AB  - The evolutionary relationships of pond frogs distributed in the Far East and
      Europe were investigated by analyses of nucleotide sequences of mitochondrial 12S
      ribosomal RNA (12S rRNA) and cytochrome b (cyt b) genes. The nucleotide sequences
      of a 412-bp segment of the 12S rRNA gene and a 534-bp segment of the cyt b gene
      were determined by the PCR-direct sequencing method using 19 frogs belonging to
      six species and one subspecies distributed in the Palearctic region. Phylogenetic
      trees were constructed by the neighbor-joining and maximum-likelihood methods
      using Rana catesbeiana or Xenopus laevis as an outgroup. The 412-bp segment of
      the 12S rRNA gene contained 65 variable sites including gap sites, and the 534-bp
      segment of the cyt b gene contained 160 variable sites. The nucleotide sequence
      divergences of the 12S rRNA gene were 0.25-4.83% within the Far Eastern frogs,
      0.25-6.22% within the European frogs, and 8.74-11.24% between the Far Eastern and
      the European frogs, whereas those of the cyt b gene were 3.64-14.73% within the
      Far Eastern frogs, 0.38-14.42% within the European frogs, and 16.53-23.58%
      between the Far Eastern and the European frogs. Although most nucleotide
      substitutions were at the third codon position of the cyt b gene and were silent
      mutations, 4 amino acid replacements occurred within the Far Eastern frogs, 4
      within the European frogs, and 11 between the Far Eastern and the European frogs.
      The phylogenetic trees constructed from the nucleotide sequence divergences
      showed slightly different topologies for the 12S rRNA and cyt b genes. R.
      esculenta from Ukraine was closely related to R. lessonae from Luxembourg in both
      the 12S rRNA and the cyt b gene sequences.

PMID- 10942616
TI  - Phylogenetic analysis of the repleta species group of the genus Drosophila using
      multiple sources of characters.
AB  - The species in the repleta group of the genus Drosophila have been placed into
      five subgroups-the mulleri, hydei, mercatorum, repleta, and fasciola subgroups.
      Each subgroup has been further subdivided into complexes and clusters. Extensive
      morphological and cytological analyses of the members of this species group have
      formed the foundation for the proposed relationships among the members of the
      repleta species group. Fifty-four taxa, including 46 taxa belonging to the
      repleta species group, were sequenced for fragments of four genes-16S ribosomal
      DNA (16S), cytochrome oxidase II (COII), and nitrogen dehydrogenase 1 (ND1) of
      the mitochondrial genome and a region of the hunchback (hb) nuclear gene. We also
      generated a partial data set of elongation factor 1-alpha (Ef1alpha) sequences
      for a subset of taxa. Our analysis used both DNA characters and chromosomal
      inversion data. The phylogenetic hypothesis we obtained supports many of the
      traditionally accepted clades within the mulleri subgroup, but the monophyly of
      taxonomic groups outside of this subgroup appears not to be supported.
      Phylogenetic analysis revealed one well-supported, highly resolved clade that
      consists of closely related members of the mulleri and buzzatii complexes. The
      remaining taxa, a wide assortment of taxonomic groups, ranging from members of
      other species groups to members of several subgroups and members of three species
      complexes from the mulleri subgroup are found in poorly supported arrangements at
      the base of the tree.

PMID- 10942617
TI  - Phylogeny of the scathophagidae (Diptera, calyptratae) based on mitochondrial DNA
      sequences.
AB  - The family Scathophagidae constitutes, together with members of the families
      Muscidae, Fannidae, and Anthomyiidae, the Muscoidea superfamily. The species
      Scathophaga stercoraria has been used extensively to investigate questions in
      animal ecology and evolution, particularly as a model system for studies of sperm
      competition and life history evolution. However, no phylogenetic studies have
      ever been performed on the Scathophagidae and the relationships within this
      family remain unclear. This study represents a molecular approach aimed at
      uncovering the phylogenetic relationships among 61 species representing 22 genera
      of Scathophagidae. A fragment of the terminal region of the mitochondrial gene
      COI (subunit I of the cytochrome oxidase gene) was sequenced in scathophagid
      species covering a wide geographic area, as well as a diverse spectrum of
      ecological habitats. Several clades grouping different genera and species have
      been identified, but the resolution power of the COI was insufficient to
      establish the exact relationships between these clades. The molecular data
      confirm the existence of a group consisting of the genera Delina, Chylizosoma,
      and Americina, which could represent the subfamily Delinae. Concerning the
      controversial position of the genus Phrosia, our data clearly suggest that it
      should be removed from the Delinae and placed within the genus Cordilura.
      Monophyly of most genera was confirmed, except for the genus Scathophaga, which
      should be divided into several different taxa.

PMID- 10942618
TI  - The anaemia of infection.
AB  - Anaemia is a common finding in infected individuals, and in many cases is an
      indicator of disease activity and/or duration. The term 'anaemia of infection'
      refers to a specific syndrome related to the more broadly defined 'anaemia of
      chronic disease'. In this syndrome, cytokines produced as part of the host
      response to infection induce anaemia by well-defined pathophysiological
      mechanisms. In this chapter, the diagnosis, significance, pathophysiology and
      treatment of the anaemia of infection will be reviewed. Other mechanisms which
      can produce anaemia in infected individuals will also be reviewed.

PMID- 10942619
TI  - Haemophagocytic syndrome associated with infections.
AB  - Haemophagocytic syndromes (HS) are the clinical manifestation of an increased
      macrophagic activity with haemophagocytosis. Pathophysiology is related to a
      deregulation of T-lymphocytes and excessive production of cytokines. The main
      clinicobiological features are fever, hepatosplenomegaly, adenopathies, skin
      rash, neurological features, cytopenias, hypertriglyceridaemia,
      hyperferritinaemia and coagulopathy. Diagnosis is based on examination of the
      bone marrow which shows benign histiocytes actively phagocytosing haemopoietic
      cells. Acquired HS are mostly associated with an underlying disease such as
      immunodeficiency, haematological neoplasias and autoimmune diseases. Infection
      associated HS was originally described by Risdall in 1979, in viral disease.
      Since the initial description HS has also been documented in patients with
      bacterial, parasitic or fungal infections. Epstein-Barr virus (EBV) is the
      causative agent in most cases. In EBV-associated HS, which sometimes has a fatal
      course, unregulated T-cell reaction or uncontrolled B-cell proliferation may
      release cytokines. Management of HS consists of early diagnosis, careful
      screening for, and prompt treatment of, infections and detection and therapy of
      any underlying disease. Prognosis of infection-associated haemophagocytic
      syndrome (IAHS) is better than that in other types of secondary HS. Management of
      cytokine imbalance should be useful to improve the outcome and reduce the
      mortality rate in these cases.

PMID- 10942620
TI  - Disseminated intravascular coagulation and purpura fulminans secondary to
      infection.
AB  - Infection is one of the commonest causes of disseminated intravascular
      coagulation (DIC). DIC is a complex disorder that results from an imbalance of
      the pro- and anticoagulant regulatory pathways. This chapter will explain the
      cellular and molecular basis of the disorder and consider the rationale behind
      current and experimental treatment strategies.

PMID- 10942621
TI  - Haematological associations of Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV) is one of eight human herpesviruses and is ubiquitous.
      Primary infection with EBV in childhood is generally silent, but often causes
      overt diseases such as infectious mononucleosis (IM) and lymphoproliferative
      disorders (LPD). The latter occurs in immunologically compromised individuals.
      Historically, EBV has been thought to be aetiologically linked to human
      malignancies such as EBV genome-positive Burkitt's lymphoma (BL) and
      nasopharyngeal carcinoma (NPC). Furthermore, studies using recent developments in
      molecular and immunological diagnostic approaches have suggested that this virus
      has a causative role in a spectrum of human diseases of previously unknown
      pathogenesis, including chronic active EBV infection syndrome (CAEBV), EBV
      related haemophagocytic lymphohistiocytosis (HLH), and certain disorders such as
      EBV genome-positive T-cell lymphoma, natural killer (NK) cell leukaemia/lymphoma,
      Hodgkin's disease (HD) and gastric carcinoma. This chapter reviews recent
      progress regarding EBV-associated diseases.

PMID- 10942622
TI  - Haematological aspects of HIV infection.
AB  - Multiple interacting factors contribute to the haematological manifestations of
      HIV disease. The effects of HIV-1 infection influence all haemopoietic cell
      lineages resulting in a spectrum of haematological abnormalities. Even in the
      absence of other pathological processes, bone marrow morphology is invariably
      abnormal, and anaemia, neutropenia and thrombocytopenia are all common during the
      course of disease. Intercurrent opportunistic infections may cause bone marrow
      suppression or induce specific cytopenias. Therapies used to treat HIV and its
      complications are frequently implicated as the cause of haematological
      dysfunction, and many have significant myelotoxic side-effects. Insights into the
      molecular basis for many of these abnormalities have permitted a clearer
      understanding of the pathophysiology of HIV-1 infection. Recombinant human growth
      factors that may be used to treat isolated cytopenias or to ameliorate the
      myelotoxic effects of other essential therapies. Lymph opoietic growth factors
      and the use of gene modified cells provide future therapeutic strategies that may
      alter the course of HIV disease.

PMID- 10942623
TI  - Human T-lymphotropic virus type 1 infection.
AB  - Human T-cell lymphotropic virus type-1 (HTLV-1) is aetiologically associated with
      adult T-cell leukaemia/lymphoma (ATL). HTLV-1 infection can also lead to various
      non-malignant diseases, for example, HTLV-1 associated myelopathy/tropical
      spastic paraparesis and HTLV-1 uveitis. HTLV-1 is endemic in southern Japan and
      the Caribbean. HTLV-1 infection is mainly transmitted by either breast-feeding,
      sexual intercourse or blood transfusions. Primary prevention of HTLV-1 in endemic
      areas by screening of blood and by refraining from breast-feeding have been
      successful. The incidence of ATL is rather low among HTLV-1 carriers (<5%). The
      precise mechanism of development of ATL remains unknown. It is a multiple-step
      process which does not require viral expression in the later stages of
      leukaemogenesis. Many samples have mutations of the tumour suppressor genes, p53
      and/or p16(INK4A). Four subtypes of ATL have been identified, each having
      distinctive clinical features. Monoclonal integration of HTLV-1 proviral DNA into
      tumour cells is found in each of the subtypes. At present, no effective therapy
      for ATL exists.

PMID- 10942624
TI  - Haematological consequences of parvovirus B19 infection.
AB  - Parvovirus B19, a member of the Erythrovirus genus, is the only member of the
      Parvoviridae family known to be pathogenic in humans. Erythroviruses are so named
      because of their tropism and selective replication in erythroid progenitor cells.
      Haematological consequences of B19 infection arise due to a direct cytotoxic
      effect on erythroid progenitors in bone marrow with interruption of erythrocyte
      production. In addition, the physiology of host haematopoiesis and competence of
      the immune response each determines clinical manifestations of B19 infection: in
      individuals with underlying haemolytic disorders, B19 infection causes transient
      aplastic crisis; in immunocompromised patients, persistent B19 infection may
      develop that manifests as pure red cell aplasia and chronic anaemia; B19
      infection in utero may result in fetal death, hydrops fetalis, or congenital
      anaemia. Diagnosis is based on examination of bone marrow and B19 virological
      studies. Treatment of persistent infection with immunoglobulin leads to a prompt
      resolution of the anaemia.

PMID- 10942625
TI  - Haematology in dengue and dengue haemorrhagic fever.
AB  - Dengue fever (DF) and dengue haemorrhagic fever (DHF) are caused by the dengue
      virus. The major pathophysiological hallmark that distinguishes DHF from DF is
      plasma leakage as a result of increased vascular permeability. Following this
      leakage, hypovolaemic shock occurs as a consequence of a critical plasma volume
      loss. Constant haematological abnormalities occurring in DHF and frequently
      include bone marrow suppression, leucopenia and thrombocytopenia. An enhanced
      immune response of the host to a secondary DV infection is a feature of DHF and
      leads to many consequences. These are immune complex formation, complement
      activation, increased histamine release and a massive release of many cytokines
      into the circulation, leading to shock, vasculopathy, thrombopathy and
      disseminated intravascular coagulation (DIC). The mechanisms underlying the
      bleeding in DHF are multiple. These are vasculopathy, thrombopathy and DIC.
      Thrombopathy consists of thrombocytopenia and platelet dysfunction. DIC is
      prominent in patients with shock. The most severe DIC and massive bleeding are
      the result of prolonged shock and cause a fatal outcome. The mechanisms of
      thrombopathy and DIC and the proper management of DHF are reviewed and discussed.

PMID- 10942626
TI  - Blood and bone marrow changes in malaria.
AB  - A variety of abnormalities in the number, morphology and function of blood and
      bone marrow cells may be found in Plasmodium falciparum and P. vivax malaria. In
      a non-immune individual, the nature of such abnormalities depends on the time
      after infection. In others it is determined by the pattern and intensity of
      malaria transmission in the area and the extent of host immunity. Severe anaemia
      may occur in children with chronic falciparum malaria and low parasitaemia as
      well as in patients with complicated acute falciparum malaria with high
      parasitaemia. However, the mechanisms underlying the anaemia in these two
      situations appear to be different. The possible roles of parasite products, T
      cell-derived cytokines produced in response to the infection, macrophage
      activation and hyperplasia, macrophage-derived factors such as tumour necrosis
      factor-alpha, and macrophage dysfunction in the pathogenesis of the
      haematological abnormalities are discussed.

PMID- 10942627
TI  - Eosinophilia and helminthic infections.
AB  - Among microbial agents, helminths are the most common cause of eosinophilia. An
      approach to the evaluation of a patient with eosinophilia is outlined, with
      particular emphasis on clues in the history, examination and routine laboratory
      data that can help with the diagnosis. Multiple helminthic infections have been
      associated with eosinophilia, and the characteristic modes of spread, clinical
      manifestations, diagnostic tests and therapeutic considerations of these
      infections are discussed.

PMID- 10942629
TI  - Preface

PMID- 10942628
TI  - Index

PMID- 10942630
TI  - The Growth Hormone Research Society.

PMID- 10942631
TI  - Reduced GLUT1 expression in Igf1-/- null oocytes and follicles.
AB  - Granulosa cells provide nutritional and trophic support for growing oocytes in
      ovarian follicles. The granulosa cells closest to the oocyte produce abundant
      insulin-like growth factor 1 (IGF1) and the IGF1 receptor is highly expressed by
      oocytes, suggesting that granulosa-derived IGF1 may have trophic effects on
      oocyte growth and development. To investigate this possibility, in the present
      study we used in situ hybridization and immunohistochemistry to examine glucose
      transporter (GLUTs 1, 3 & 4) expression in follicles from pre-pubertal Igf1-/-
      and littermate wildtype (wt) mice. Pre-pubertal mice were used for this study
      because the Igf1 null mice do not mature sexually. GLUT1 mRNA and
      immunoreactivity were most abundant in oocytes and in granulosa cells immediately
      surrounding the oocyte. Expression of this transporter was significantly reduced
      in Igf1 null oocytes and granulosa cells and was restored by exogenous IGF1
      treatment to wt levels. These effects on GLUT expression were significant at both
      the mRNA and immunoreactive protein levels. Oestrogen treatment significantly
      increased GLUT1 levels in oocytes and granulosa from both wt and Igf1-/-,
      although the latter were still significantly lower than wt. Oocyte glycogen
      stores, determined by PAS staining, did not appear different in Igf1-/- and wt
      mice.GLUT3 was expressed in thecal cells surrounding growing follicles and was
      not appreciably different in Igf1 null compared with wt ovaries. GLUT4 expression
      was not detected in the prepubertal mouse ovary. Together with observations from
      previous studies showing that ovulation is blocked in Igf1 null mice, the present
      data suggest that IGF1's augmentation of granulosal and oocyte GLUT1 expression
      may be essential for oocyte maturation and successful ovulation.

PMID- 10942633
TI  - GH receptors and signalling

PMID- 10942632
TI  - A nine-month, placebo-controlled study of the effects of growth hormone treatment
      on lipoproteins and LDL size in abdominally obese men.
AB  - Abdominal/visceral obesity is associated with blunted growth hormone (GH)
      secretion and an unfavourable lipoprotein pattern. In this study, the effect of
      GH treatment on LDL size and on serum lipoprotein concentrations was determined
      in abdominally obese men. Thirty men, aged 48-66 years, with a body mass index
      (BMI) of 25-35 kg/m(2)and a waist:hip ratio of >0.95, received treatment with GH
      (9. 5 microg/kg/day) or placebo for 9 months. Serum concentrations of total
      cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein
      B (apoB) were reduced (P<0.05, P<0.05 and P<0.001 vs placebo, respectively).
      Serum lipoprotein(a) [Lp(a)] concentration increased (P<0.05 vs. placebo). Mean
      low density lipoprotein (LDL) particle diameter was marginally increased by
      active treatment as compared with placebo (P =0.08). No changes were observed in
      the serum concentrations of high density lipoprotein-cholesterol (HDL-C),
      apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE). In conclusion, 9 months
      of GH treatment in abdominally obese men beneficially reduced serum
      concentrations of TC, LDL-C and apoB, and marginally increased mean LDL diameter,
      while serum Lp(a) increased. The ultimate effect of GH therapy on the
      cardiovascular risk remains, however, to be determined.

PMID- 10942634
TI  - Drug-resistant viral hepatitis.

PMID- 10942635
TI  - Multi-drug resistant HIV-1.

PMID- 10942636
TI  - Clinical isolates of Staphylococcus aureus exhibit diversity in fnb genes and
      adhesion to human fibronectin.
AB  - OBJECTIVES: The fibronectin-binding proteins (FnBPs) of Staphylococcus aureus are
      involved in the pathogenesis of infection, but their characteristics in clinical
      isolates are incompletely defined. The aim of this study was to evaluate
      phenotypic and genotypic characteristics of the FnBPs of a large collection of
      recent isolates. METHODS: The adherence of 163 S. aureus isolates to immobilized
      fibronectin was compared with that of S. aureus 8325-4 using a microtitre assay.
      The presence of the genes encoding the fibronectin-binding proteins FnBPA and
      FnBPB was evaluated by Southern dot blot using probes specific for region A of
      fnbA or fnbB. RESULTS: The adherence of clinical isolates to fibronectin
      (expressed as a percentage of the mean adherence of S. aureus 8325-4) was 56%
      125% for 155 isolates (95%), and less than 20% for eight isolates (5%). Adherence
      of the bacterial group associated with orthopaedic implant-associated infection
      was significantly greater than that for isolates associated with nasal carriage,
      endocarditis, or septic arthritis/osteomyelitis. Southern dot blot demonstrated
      that 126/163 isolates had two genes (77%) and 37/163 had one detectable gene
      (23%). There was no difference in adherence between isolates with one or two fnb,
      but isolates associated with invasive disease (endocarditis or primary septic
      arthritis and/or osteomyelitis) were more likely to have two genes. CONCLUSIONS:
      These data demonstrate diversity in the FnBPs of clinical isolates of S. aureus.
      The findings suggest that the interplay between pathogenesis and a single
      virulence determinant is unlikely to be a uniform process across a spectrum of
      infections. This confirms the need to extend the study of staphylococcal
      pathogenesis from the laboratory to non-uniform populations of clinically
      relevant isolates.

PMID- 10942637
TI  - Molecular mimicry in infectious encephalitis and neuritis: binding of antibodies
      against infectious agents on Western blots of human nervous tissue.
AB  - OBJECTIVES: To study the occurrence of cross-reactivities of antibodies against
      infectious agents with human nervous tissue. METHODS: Binding of 25 antibodies
      against 17 neurotropic pathogens comprising Borrelia burgdorferi, Toxoplasma
      gondii, and various DNA and RNA viruses to Western blots of human cortex and
      myelin from central and peripheral nervous system was investigated. RESULTS:
      Fourteen of the 25 antibodies tested showed binding to Western blots of human
      nervous tissue, suggesting the presence of shared epitopes. Binding of 11
      antibodies against 10 pathogens to cortex and/or myelin correlated with the
      tissue targeted by neuropathological lesions. Three antibodies did not show such
      correlation; 11 antibodies did not bind at all. CONCLUSIONS: Our results suggest
      that shared epitopes between infectious agents and human nervous tissues are more
      common than previously expected. Thus, molecular mimicry should be considered
      more frequently as a possible pathogenetic mechanism, among others, inducing
      tissue damage in encephalitis and neuritis caused by various pathogens.

PMID- 10942638
TI  - Prevalence of HIV among pregnant women in Dundee 1988-1997: evidence to gauge the
      effectiveness of HIV prevention measures.
AB  - OBJECTIVES: During November 1988-July 1990, an HIV prevalence survey of pregnant
      women in Dundee, which used a combined voluntary diagnostic testing and voluntary
      unlinked anonymous approach, revealed a rate of 0.3%, the highest recorded
      prevalence among such a population in the U.K. at the time. To determine if, and
      why, any changes in HIV prevalence had occurred during the early to mid 1990s,
      further studies were conducted. METHODS: During January 1993-December 1997,
      antenatal patients of, and women undergoing therapeutic termination of pregnancy
      at, Ninewells Hospital, Dundee, were offered a diagnostic HIV antibody test. For
      those declining, residual sera from rubella specimens were tested for HIV
      antibodies using an unlinked anonymous approach which did not necessitate the
      securement of informed consent. Information about injecting drug use was obtained
      from all women and linked to their HIV test results. RESULTS: For all pregnant
      women, a significant decline in HIV prevalence (P<0.05) from 0.3% (19/6228)
      during 1988-1990 to 0.12% (22/17899) during 1993-1997 was observed. For those who
      injected drugs, prevalence decreased significantly (P<0.05) from 27.5% (11/40) to
      7% (6/85), while among women who had never injected drugs prevalence decreased
      slightly, but not significantly (P>0.05), from 0.13% (8/6188) to 0.09%
      (16/17814).Prevalence in the non-injectors who reported no sexual intercourse
      with an injector was low at 0.04% (8/17682) during 1993-1997. No significant
      trends in HIV prevalence were seen over the 5 years up to 1997. CONCLUSION: The
      decline in HIV prevalence among pregnant women in Dundee during the early to mid
      1990s can be explained predominantly by the control of HIV transmission among the
      city's injectors, and from them to the wider heterosexual population. It is
      likely that interventions designed to reduce needle/syringe sharing among
      injectors have been successful. It is imperative that the preventive effort is
      not allowed to be weakened.

PMID- 10942639
TI  - Does blood type B protect against haemolytic uraemic syndrome? An analysis of the
      1996 Sakai outbreak of Escherichia coli O157:H7 (VTEC O157) infection. The Osaka
      HUS Critical Care Study Group.
AB  - OBJECTIVES: Expression of the P1 blood type antigen is suggested to have a
      protective effect against post-enteropathic haemolytic uraemic syndrome (HUS).
      The B blood type may also protect against HUS, since terminal trisaccharide
      sequences similar to those of the B blood type determinants are reported to have
      an affinity to Vero cytotoxin that is 23% as strong as that of the P1
      determinants. Thus, we studied whether ABO blood types were related to the
      occurrence or severity of HUS. METHODS: We obtained clinical and laboratory data
      of 49 HUS patients treated in 14 critical care facilities during the 1996
      Escherichia coli O157:H7 outbreak in Sakai, Japan. We retrospectively studied
      whether ABO blood types were related to the occurrence or severity of HUS.
      RESULTS: The numbers of patients with blood types A, B, O or AB were 29, 8, 12,
      and 0, respectively. For each blood type, the number of patients with severe
      renal complications was 16, 6, 9, and 0, respectively. The distribution of blood
      types among the HUS patients deviated from a population-based distribution of
      blood types (P<0.05, Chi-squared test); i.e., the frequency of the A blood
      phenotype was significantly higher among our HUS patients. However, there was no
      significant difference in the frequency of patients with the A antigen (A and AB
      blood groups) among our HUS patients, whereas the frequency of B antigen
      expression was significantly lower (P<0.05, Chi-squared test). The risk of severe
      renal complications did not appear to be related to ABO blood types. CONCLUSIONS:
      Our data suggest that expression of the B antigen has a protective effect against
      the onset of HUS, but that it does not affect the severity of the disease.

PMID- 10942640
TI  - Adherence, side effects and efficacy of stavudine plus lamivudine plus nelfinavir
      in treatment-experienced HIV-infected patients.
AB  - OBJECTIVES: To evaluate adherence, side effects and efficacy of a modality of
      highly active antiretroviral therapy (HAART) in HIV-infected patients. METHODS:
      In a cohort, prospective study, 65 previously treated patients received stavudine
      plus lamivudine plus nelfinavir. Fifty-three participants (81%) had a history of
      intravenous drug use. Patients were evaluated at 3-month intervals. The
      association of adherence with demographic variables, hepatitis C virus infection,
      number of stopped antiretroviral regimens, HIV RNA level, CD4 cell count, and
      adverse effects to drugs was assessed. RESULTS: After a median follow-up of 12
      months, 30 participants (46%) showed adequate adherence in all visits. An
      association was observed between adherence and female sex: 18 of 47 men (38%) vs.
      12 of 18 women (67%) presented adequate adherence in all visits (P=0. 0416). An
      association was also observed between adherence and low baseline HIV RNA level
      (P=0.0229). Discontinuation of treatment took place because of refusal to take
      medication in 11 participants (17%) and because of side effects in seven
      participants (11%). Undetectable HIV RNA level was achieved in 26 patients (40%)
      at 3 months and in lower percentages at months 6, 9 and 12. CONCLUSIONS: Overall
      adherence to the employed HAART regimen was poor. Female sex and low baseline HIV
      RNA were associated with better adherence. Refusal to take medications and side
      effects were the main reasons to stop therapy. At 3 months' follow-up,
      virological efficacy was achieved in 40% of patients.

PMID- 10942641
TI  - The reproducibility of sputum gram film interpretation.
AB  - OBJECTIVES: To evaluate the reproducibility with which microbiologists interpret
      Gram-stained sputa and examine the effect of the smear preparation method.
      METHODS: Two hundred and ten coded slides prepared directly from a purulent
      portion of sputum (DS) and 140 slides prepared after homogenization of the same
      sputum (HS) were examined by three experienced microbiologists. A proportion of
      the slides prepared by each method were recorded and represented to the raters.
      Intraobserver and interobserver variation was assessed using the kappa statistic
      (kappa). RESULTS: Evaluation of the smear as being infected and predicting
      Streptococcus pneumoniae as the infecting organism showed the greatest
      intraobserver agreement (kappa=0.74-0.82) and interobserver agreement (kappa=0.50
      0.82). The agreement concerning the number of cells and infection with
      Haemophilus influenzae was only fair to moderate. Differences in the
      interpretation of smears prepared by the two methods could be explained by the
      intrinsic disagreement that occurs when the same smear is examined twice. The
      positive predictive value of a positive S. pneumoniae smear for a positive
      culture ([10(6)/ml) was 81% with the DS and 97% with the HS. CONCLUSION: In this
      laboratory, a sputum Gram film interpretation suggesting infection with S.
      pneumoniae was reproducible and predictive of a significant positive culture.

PMID- 10942642
TI  - Tuberculosis of the central nervous system in children: a 20-year survey.
AB  - OBJECTIVE: To review our experience of central nervous system (CNS) tuberculosis
      at a major British paediatric tertiary referral centre, following the
      introduction of CT Scan facilities. METHODS: This was a retrospective case survey
      (prospective in nine patients) of patients admitted to Great Ormond Street over a
      20-year period (1977-1997), who fulfilled criteria for a diagnosis of CNS
      tuberculosis. Data were collected with regard to the clinical, laboratory and
      demographic characteristics of patients, as well as results of radiological
      investigations and data on clinical outcome. RESULTS: We identified 38 children
      with CNS tuberculosis: 23 with tuberculous meningitis (TBM), 10 with tuberculous
      meningitis and associated tuberculomas and five with tuberculomas alone. The mean
      age of this group was 3.7 years, ranging from 8 months to 16 years. Only 14 (37%)
      were of Caucasian origin. A contact source was identified in 18 patients (47%).
      Previous BCG had only been given to six (16%). The main clinical symptoms and
      signs present on admission were alteration in consciousness in 30 patients (79%),
      focal neurological signs in 25 (66%) and fever in 25 (66%). Seizures were
      observed in 20 patients (53%) and meningism in 18 (47%). Mycobacterium
      tuberculosis was either cultured or identified by acid-fast stain from CSF or
      brain tissue from 24 patients (63%). The Mantoux reaction was positive in 17/33
      (51%); abnormalities of the chest X-ray were found in 15 (40%). Cranial CT scans
      of the patients presenting with TBM showed hydrocephalus in 31 patients (94%),
      and basilar enhancement in 27 (93%) out of the 29 patients who received
      intravenous contrast. Anti-tuberculous therapy administered varied according to
      current recommendations of the period; concurrent steroids were given to 31
      patients (82%). Neurosurgical procedures were required in the majority of
      patients with TBM, 25 (76%). In five patients with TBM, new tuberculoma developed
      during treatment. The overall mortality for our group of patients was 13%, whilst
      permanent neurological sequelae were seen in 47% of the patients. None of the
      patients who received BCG either died or had severe sequelae. Mortality and
      morbidity rates were higher in the first 10 years of the study and amongst those
      patients admitted in Stage III disease. CONCLUSIONS: CNS tuberculosis continues
      to be a condition which carries significant morbidity and mortality. Early
      diagnosis and prompt initiation of treatment are essential to improve the poor
      outcome.

PMID- 10942644
TI  - Assessment of antibiotic prescription in acute respiratory infections in adults.
      The Spanish Study Group on Antibiotic Treatments.
AB  - OBJECTIVE: This study aims to ascertain the variability in the use of antibiotics
      for the treatment of acute respiratoryinfections in several hospital emergency
      services in Spain, as well as the appropriateness of antibiotics prescription
      through evaluation by a panel of experts using available scientific evidence.
      METHOD: A cross-sectional study was carried out in the emergency services of 10
      hospitals in different Spanish regions. We chose patients diagnosed as having
      acute respiratory infection, aged over 14 years. Among the collected variables
      were: type of respiratory infection, antibiotic prescription, comorbidity,
      qualification of the prescribing doctor and hospital admission. The consensus
      conference held by a panel of experts established first choice treatment and the
      alternative and inappropriate use for each respiratory infection, based on the
      available scientific evidence. All the observed prescriptions in our study were
      classified according to this pattern. RESULTS: A sample of 2899 acute respiratory
      infections was studied (5.5% of all emergencies). Antibacterial agent treatment
      was prescribed in 82.6% of these, varying according to the infection between
      98.5% of pneumonias and 49% of croup-influenza-common cold. The most commonly
      used antibiotics were amoxicillin-clavulanate and cefuroxime. The global
      percentage of inappropriate prescription was 40.5% (95% CI; 35.4-45.5). The
      prescriptions were inappropriate in 16.9% of cases of pharyngotonsillitis, 17.8%
      of chronic bronchitis, 26.9% of acute bronchitis, 29.3% of pneumonias, 30.8% of
      otitis and sinusitis and in 70.8% of croup, flu, common cold and non-specified
      infections. Significant variability among participating centres was observed,
      both in choice of antibiotics and in their degree of appropriateness.
      CONCLUSIONS: There is excessive use of antimicrobial drugs in acute respiratory
      infections, and the majority are used for viral infections. There is
      indiscriminate use of broad spectrum antibiotics, which are valid in some
      infections but clearly inappropriate in others. Similarly, there are important
      differences in the choice of antibiotics and their degree of appropriateness
      among hospitals.

PMID- 10942643
TI  - Persistence of viruses in upper respiratory tract of children with asthma.
AB  - OBJECTIVES: Nasopharyngeal swabs of 50 asthmatic children in the symptom-free
      period were examined for the presence of adenoviruses, rhinoviruses and
      coronaviruses. A control group of 20 healthy individuals was included in this
      study. METHODS: A polymerase chain reaction was used to detect adenovirus DNA and
      rhinovirus and coronavirus complementary DNA. The fragments of amplified genetic
      material were visualized with the use of agarose gel electrophoresis. RESULTS:
      Adenovirus DNA was found in 78.4% of asthmatic children, rhinovirus RNA in 32.4%
      and coronavirus RNA in 2.7%. Adenovirus DNA was detected in one of the 20
      nasopharyngeal swabs of healthy controls; the rest of the control samples were
      negative. CONCLUSIONS: The persistent presence of viruses in the upper
      respiratory tract of asthmatic children shows a possible connection between viral
      infections and asthma.

PMID- 10942645
TI  - Vertebral osteomyelitis caused by Streptococcus agalactiae.
AB  - Streptococcus agalactiae is a rare cause of vertebral osteomyelitis. We present
      four cases of spondylitis caused by this micro-organism and a review of 20 cases
      previously described in the literature. Only seven patients (29%) were under 50
      years of age. Diabetes mellitus and neoplasms were the most frequent underlying
      conditions, although 37.5% of the patients did not have any predisposition. Neck
      or back pain was the most common symptom. Diagnosis depended mainly on magnetic
      resonance imaging. Blood cultures were positive in 50% of the patients. The
      duration of antibiotic therapy was 6 weeks for most patients. The outcome was
      favourable, with none of the patients suffering serious sequelae.

PMID- 10942646
TI  - Favourable outcome of haemolytic uraemic syndrome in an HIV-infected patient
      treated only with prednisone.

PMID- 10942648
TI  - Breast implant infection in a cat owner due to Pasteurella multocida.

PMID- 10942647
TI  - A rare infection caused by Chryseomonas luteola.

PMID- 10942649
TI  - Salmonella infantis osteomyelitis in sickle cell disease.

PMID- 10942650
TI  - Does Helicobacter pylori colonize the vagina of pregnant women?

PMID- 10942651
TI  - Comparisons of hepatitis B and C and HIV prevalence rates.

PMID- 10942652
TI  - Filamented Pseudomonas aeruginosa and a markedly high level of endotoxin in
      cerebrospinal fluid.

PMID- 10942653
TI  - An unusual case of pulmonary abscess.

PMID- 10942654
TI  - What's new in HIV
AB  - This issue goes to press as the world media turns its eyes on the World Aids
      Conference being held in Durban, South Africa. No doubt "the gap" in HIV care
      provision between developed and developing nations which the last congress in
      Geneva sought to bridge will seem wider than ever. Reports from the conference
      will follow in future issues, but in this one we focus on problems commonly faced
      by clinicians primarily caring for intravenous drug users. Mark Wright and Janice
      Main give an overview of the management of co-infection with HIV and Hepatitis C
      viruses, and Ray Brettle discusses the difficulties of antiretroviral selection
      in the context of methadone and other recreational drug use. Copyright 2000 The
      British Infection Society.

PMID- 10942655
TI  - Shifting sands in a pluralist world. Good practice: a guide for neurosurgeons.
      World Federation of Neurosurgical Societies European Association of Neurosurgical
      Societies.

PMID- 10942656
TI  - The Australian Association of Neurologists--50 years of age.

PMID- 10942657
TI  - The development of a concept of mild head injury.
AB  - Medical and literary sources have described head injury and its effects from
      early Egyptian times. Though milder injury - concussion - must have been
      familiar, there was little specific written about it until the latter part of the
      18th century. Descriptions of persisting symptoms appear in the 19th century, and
      discussion of their origin and management has continued and intensified since
      then. There have been several major issues. How does mechanical trauma produce a
      temporary loss of neurological function and is there some lasting damage? When
      symptoms persist do they follow a pattern which we recognise as occurring with
      structural lesions, or are the symptoms a functional reaction to the injury and
      other life events? Are they both?Over the last 50 years these issues have been
      debated, often with heat. Whatever the final judgment the present task would seem
      to be to provide a service to deal with the clinical situation.

PMID- 10942658
TI  - The current use of botulinum toxin.
AB  - Botulinum toxin is the most potent neurotoxin known, and has been in clinical use
      since the late 1970s. The toxin inhibits the release of acetylcholine from nerve
      terminals by inhibiting transport of the synaptic vesicles, thus causing
      functional denervation lasting up to 6 months. Our understanding of the mechanism
      of action of the toxin and the spectrum of diseases treatable with this agent
      continues to increase. Efficacy has been demonstrated in hemifacial spasm,
      dystonia, spasticity, hyperhidrosis and other conditions. Alternative serotypes
      are used in some centres, generally after the development of immunoresistance to
      the standard toxin (serotype A), and are likely to be in routine use in the near
      future. This paper reviews the history, pharmacology and current uses of
      botulinum toxin.

PMID- 10942659
TI  - Symptomatic lumbar spinal arachnoiditis: fact or fallacy?
AB  - It is generally accepted that chronic adhesive lumbar arachnoiditis is a cause of
      symptoms, notably back pain and/or pain (of almost any type, not necessarily
      'anatomical') in the lower limbs, although there is no clearly defined clinical
      pattern which is clearly associated with this syndrome. There is no doubt that
      arachnoiditis occurs as a pathological and radiological entity due to a number of
      causes. In the view of the present authors, the nexus between the pathology and
      radiology on the one hand, and the patients' symptoms on the other hand, has not
      been demonstrated with any degree of scientific rigor.

PMID- 10942660
TI  - The postconcussion syndrome after mild head trauma: is brain damage
      overdiagnosed? Part 1.
AB  - Many investigators attribute the postconcussion syndrome following mild closed
      head injury to permanent brain damage. The evidence supporting this conclusion is
      reviewed, including the force necessary to cause permanent brain damage; the
      basis for determining whether the patient was exposed to sufficient force in the
      accident to permanently damage the brain; the basis for determining whether the
      patient actually has permanent brain damage (not just brain dysfunction)
      traceable to the accident; and whether the location and severity of brain damage
      is sufficient to account for the postconcussion syndrome. CONCLUSION: the
      evidence for permanent traumatic brain damage as the cause of the postconcussion
      syndrome following mild closed head injury is weak.

PMID- 10942661
TI  - The efficacy of spinal cord stimulation for chronic pain.
AB  - A prospective study was undertaken to evaluate the efficacy of spinal cord
      stimulation (SCS) in the management of chronic pain syndrome. The study included
      all patients who underwent this procedure at the Royal Melbourne Hospital and the
      Melbourne Private Hospital over a period of two years. A total of 29 patients
      were managed by the end of June 1996. These patients were carefully screened by a
      neurosurgeon (JVR) and a psychiatrist. Of these, 26 patients had a follow up
      evaluation at the end of August 1996. From the group of 29 patients, four
      patients failed to obtain any relief during the trial phase of the procedure and
      thus did not have the stimulator implanted permanently. From the 25 patients who
      proceeded to have the stimulator implanted, 11 patients had a variable beneficial
      response, three patients found it to be of marginal benefit, six had no benefit,
      three patients initially had a good response but subsequently gained no benefit
      whilst two patients were uncertain of its benefit. It thus appears that SCS was
      of benefit in 50% of our carefully selected patients with chronic pain syndromes.

PMID- 10942662
TI  - Accuracy and clinical applicability of a passive marker based frameless
      neuronavigation system.
AB  - A passive marker system permits the inclusion of an unlimited number of
      instruments and other devices during frameless stereotaxy. The aim of this study
      was to evaluate the accuracy and clinical applicability of a passive marker based
      frameless image guided system (VectorVision; BrainLab, Heimstetten, Germany)
      developed for surgical planning and intraoperative image guidance. The system was
      first applied to a plastic phantom to determine the accuracy of the system by
      measuring the difference between the actual probe position and its analogous
      position on the monitor screen. The navigational device was subsequently applied
      to 40 procedures for brain tumours and cavernomas. The mean error value between
      the image on the monitor screen and the real location in the phantom and the
      clinical study was 1.45 mm (+/-0.99) and 4.05 mm (+/-3.62), respectively. Many
      different instruments could be employed as pointing devices. It was helpful in
      minimising the size of the craniotomy. An average lengthening of the surgical
      procedure of 20 minutes was experienced. The neuronavigation system proved to be
      a useful surgical tool to approach and detect lesions larger than 5 mm in
      diameter. The passive marker technology is intuitive and enables the surgeon to
      use his or her own instruments at any time as a pointing device, thus avoiding
      further costs for specially designed surgical equipment.

PMID- 10942663
TI  - Experience in surgical management of tumours involving the cavernous sinus.
AB  - Potential injury to the neurovascular structures within the cavernous sinus often
      prohibits aggressive removal of tumours involving it, however, fully
      understanding the anatomy and selecting an appropriate surgical approach can
      often resolve this problem with acceptable morbidity. Moreover, a tumour may
      originate from different anatomical structures of the cavernous sinus which will
      influence the difficulty and outcome of the surgery. In general, tumours in this
      region can be classified as intradural, intracavernous and invasive types. The
      strategy of surgical treatment varies among these different anatomical types.
      Therefore, preoperative evaluation of tumours in the cavernous sinus is critical
      for the selection of an appropriate microsurgical approach. During the past 5
      years, 12 tumours involving the cavernous sinus have been operated upon which
      included four neuromas, three meningiomas, three cavernous haemangiomas, one
      plasmacytoma and one chondroma. Nine of these twelve tumours were totally
      resected after one or two operations. There was no surgical mortality and the
      most common morbidity was transient cranial nerve palsy. At 2 months after
      surgery there was no additional postoperative cranial nerve deficit in all the
      patients; however, one patient developed a postoperative middle cerebral artery
      infarct due to accidental injury to the internal carotid artery during surgery.
      The respectability of the tumour mostly depends on its consistency and the
      involvement of the adjacent anatomy. The pathoanatomical features of the tumours
      and the clinicoradiological findings, as well as the selection of the
      microsurgical approach, are discussed.

PMID- 10942664
TI  - Music and cerebral hemodynamics.
AB  - Previous studies performed by positron emission tomography and Transcranial
      Doppler (TCD) found a different cerebral activation during musical stimuli in
      musicians compared to non-musicians. The aim of our study is to evaluate by means
      of TCD, possible different pattern of cerebral activation during the performance
      of different musical tasks in musicians, non-musicians and lyrical singers. Our
      findings show a left hemispheric activation in musicians and a right one in non
      musicians. Preliminary data on lyrical singers' activation patterns need further
      confirmation with a larger population. These data could be related to a different
      approach to music listening in musicians (analytical) and non-musicians who are
      supposed to have an emotional approach to music.

PMID- 10942665
TI  - Selection of treatment modalities for cerebral arteriovenous malformations: a
      retrospective analysis of 348 consecutive cases.
AB  - The objective was to establish the selection criteria for the optimal management
      modalities for cerebral arteriovenous malformations. We analysed the
      complications and late outcomes in 348 consecutive cases (132 microsurgical
      resections, 202 stereotactic radiosurgeries, 8 embolisations only, 6 combined
      treatments) managed at Yonsei University Hospital from 1988 to 1997. Files for
      all patients were analysed. The outcome was classified into good for the patients
      who returned to their previous job with or without neurological deficits, fair
      for the patients who were unable to return to work but performed daily activities
      independently with minor deficits, and poor for the patients who were performing
      dependent daily activities with major deficits. The outcome of microsurgery was
      considered good in 108 patients (81.8%), fair in 18 (13.6%), poor in 4 (3.1%),
      and 2 (1.5%) patients died. Initial insults and haemodynamic complications were
      the major cause of an unfavourable outcome. The cumulative occlusion rate of the
      nidus after radiosurgery was 10.2% within 12 months, 75.3% within 24 months, and
      89.8% within 36 months. Perilesional imaging changes with neurological deficits
      (4 permanent and 6 transient, 4.8%) and haemorrhage (16 patients, 7.7%) during
      the latent interval were the major cause of an unfavourable outcome (1 poor, 4
      dead after radiosurgery). Postradiosurgery bleeding occurred frequently within 6
      months (6 patients), and between 13 and 24 months (8 patients). In conclusion,
      selection of treatment modality for cerebral AVMs depends on the preoperative
      evaluation of the risk/benefit ratio in each case. Microsurgical removal, which
      eliminates the risk of bleeding immediately, is preferred for lesions in non
      eloquent areas. Radiosurgery is an effective treatment modality for small lesions
      in eloquent areas, but has a substantial risk of haemorrhage during the latency
      period. Results of this study suggest that microsurgical removal should be
      considered for lesions in eloquent areas with high haemorrhage risk, such as
      prior haemorrhage, medium to large size lesion, and single deep venous drainage.

PMID- 10942667
TI  - Minimally invasive surgical exposure of the extreme high cervical internal
      carotid artery: anatomical study.
AB  - The purpose of this study is to investigate a minimally invasive access to a high
      cervical lesion involving the internal carotid artery. Using 13 fixed cadaveric
      preparations, we sought to design a surgical approach that would cause minimal
      involvement of the surrounding structures and maximal exposure to the extreme
      high cervical area. This technique preserves the function and integrity of the
      mandible, sternocleidomastoid, posterior belly of digastric and styloid process
      muscles. The method uses retraction and mobilisation of those muscles, as well as
      decompression of the facial from the stylomastoid foramen. The internal carotid
      artery is exposed up to the entry point into the carotid canal. The cranial
      nerves IX, X, XI and XII are kept in sight up to the jugular foramen. This
      approach creates a wide corridor into the deep high cervical and inferior cranial
      base area and can be utilised for high cervical carotid lesions and tumours
      related to the artery.

PMID- 10942666
TI  - The occurrence of autoimmune diseases in patients with multiple sclerosis and
      their families.
AB  - The aims of this study were to determine whether the occurrence of autoimmune
      diseases is increased in patients with multiple sclerosis (MS) and their families
      and whether this is influenced by the type of MS. We conducted a case-control
      study using a questionnaire design to determine whether the prevalence of 11
      autoimmune diseases is increased in patients with MS and their first-degree
      relatives compared to a random population control group and their first-degree
      relatives. We found that the total combined prevalence of the 11 autoimmune
      diseases was higher in the MS patients than in the controls, with an odds ratio
      of 1.7 (95% confidence interval 0.9-3.2; P = 0.10) increasing to 1.9 (1.0-3.5; P
      = 0.05) after adjusting for age. For persons aged under 60 years, the odds ratio
      was 2.3 (1.1-4.6). We also found that there was a significant increase in the
      total combined prevalence of the autoimmune diseases in the first-degree
      relatives of MS patients compared to the first-degree relatives of the control
      group (P = 0.003, odds ratio 2.2, confidence interval 1.3-3.7). Patients with
      primary progressive MS did not differ from patients with relapsing-remitting or
      secondary progressive MS in the personal or familial occurrence of autoimmune
      disease. In conclusion, although there were sources of possible bias, this study
      suggests that individuals with MS have a genetic predisposition to autoimmunity
      in general.

PMID- 10942668
TI  - Petrosal approach for a large right posterior cerebral artery (P2) aneurysm.
AB  - A seven year old girl presented with recurrent headaches Computed tomography (CT)
      magnetic resonance imaging (MRI) and angiography showed a 2 cm aneurysm at the P2
      segment of the right posterior cerebral artery. The aneurysm was trapped
      successfully by a petrosal approach. The patient made an excellent recovery
      except for a transient fourth nerve palsy.

PMID- 10942669
TI  - World Federation of Neurosurgical Societies European Association of Neurosurgical
      Societies Good practice: a guide for neurosurgeons.

PMID- 10942670
TI  - The Holmes-Adie plus syndrome.
AB  - A clinical syndrome of tonic pupil associated with tendon areflexia was first
      described by Holmes and Adie; autonomic neuropathy and peripheral neuropathy can
      be associated. The postulated mechanism of areflexia in Holmes-Adie syndrome is a
      synaptic disorder of the spinal reflex pathways. We report a case of a Holmes
      Adie syndrome variant with hitherto unreported cranial neuropathy. A 41 year old
      woman developed insidious onset of sensory symptoms related to her left
      trigeminal and chorda tympani nerves over a few months. Physical examination
      showed generalised tendon areflexia and a left sided Adie's pupil. Imaging did
      not reveal any structural abnormality. Electrophysiological studies demonstrated
      an absent blink reflex on stimulating the left supraorbital and infraorbital
      nerves. These findings were suggestive of a dysfunction affecting the brain stem
      reflex arc. The pathophysiological process of Holmes-Adie syndrome may be more
      widespread than previously thought.

PMID- 10942671
TI  - Cellular blue naevus of the scalp with brain invasion.
AB  - A case of a 28 year old woman with an intracranial cellular blue naevus (CBN)
      which was believed to be the extension from a pigmented skin/scalp lesion is
      reported. There was no similar pigmented skin lesion noted on other parts of her
      body. Radical intervention, including wide excision of the affected skin of the
      scalp, removal of the underlying pigmented skull bone and wide excision of the
      pigmented dura, together with wide excision of the intracranial mass, were
      performed. The skin defect was covered by rotation flap and free skin graft. The
      dura was closed by grafting with fascia lata. The skull defect was left open and
      would be repaired later at a second planned surgery.

PMID- 10942672
TI  - Chronic inflammatory demyelinating polyneuropathy associated with membranous
      glomerulonephritis: case report.
AB  - A case of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) with
      Membranous Glomerulonephritis (MGN) is reported. This is the second case recorded
      in the literature and the article compares this case with the other reported
      case, including immunological implications.

PMID- 10942673
TI  - Expressive language disorder after infarction of left lentiform nucleus.
AB  - A 53 year old bilingual woman presented with apraxia of speech and writing in
      English and German after ischaemic infarction of the left posterior lentiform
      nucleus. Detailed language assessment revealed impairments of articulation,
      verbal fluency, auditory repetition, interpretation of complex semantic
      relationships, formulation of definitions and verbal short-term memory. The case
      illustrates the role of the basal ganglia in speech planning, word retrieval and
      verbal short-term memory.

PMID- 10942674
TI  - Asymptomatic schwannoma of the oculomotor nerve: case report.
AB  - Intracranial oculomotor schwannoma without neurofibromatosis is rare and is
      usually symptomatic. Only one case of asymptomatic oculomotor schwannoma has been
      previously reported. We present a case of intracranial oculomotor schwannoma
      which caused no signs or symptoms. Microsurgical resection of this tumour
      resulted in oculomotor palsy. We reviewed 7 reported cases and the findings
      indicated that radical removal of the tumour invariably caused or worsened the
      oculomotor palsy. The reason why the tumour caused no symptoms in this case was
      unclear. However, improvements in diagnostic methods such as magnetic resonance
      imaging (MRI) may increase the detection of such asymptomatic cases. Indications
      for surgical treatment should be established.

PMID- 10942675
TI  - Ruptured spinal arteriovenous malformation causing cauda equina syndrome: case
      report.
AB  - We describe the case of an acute cauda equina syndrome secondary to a confined
      subarachnoid bleed from a spinal arteriovenous malformation. The patient was
      elderly and made a complete neurological recovery following surgery.

PMID- 10942676
TI  - Rathke's cleft cyst with large frontal extension: unusual shape and
      pathomechanism of its formation.
AB  - The patient was a 62 year old woman who presented with a visual field defect.
      Magnetic resonance images showed an intra-and supra-sellar low intensity mass on
      T1 weighted images. The preoperative diagnosis was craniopharyngioma, Rathke's
      cleft cyst (RCC) or arachnoid cyst. The patient underwent transsphenoidal surgery
      & the pathological diagnosis was RCC. We conclude that although RCC has a round,
      ovoid or dumb-bell shaped configuration, it may present a unusual shape in cases
      with preconditions, as were seen in our patient.

PMID- 10942677
TI  - 'Chemotherapy is useful in treatment of gliomas'.

PMID- 10942678
TI  - Counterpoint--chemotherapy is useful in the treatment of gliomas.

PMID- 10942680
TI  - News and notices

PMID- 10942679
TI  - Chemotherapy is useful in the treatment of gliomas. Discussant.

PMID- 10942681
TI  - Diary of events

PMID- 10942682
TI  - Tourniquets in arterial bypass surgery.
AB  - BACKGROUND: successful infra-popliteal bypass depends on precise, atraumatic
      technique in performing the distal anastomosis. The use of a tourniquet
      facilitates the distal anastomosis, reducing dissection, avoiding traumatising
      clamping of the vessels and providing an "uncluttered" operating field. Despite
      these advantages the technique is under-used. OBJECTIVES: to review the use of
      tourniquets in arterial reconstruction, with particular reference to safety
      issues and complications. DESIGN, METHODS AND MATERIALS: a Medline search was
      performed (last search Feb. 2000), and keywords from relevant papers were used to
      perform subsequent searches. References were reviewed from each relevant paper.
      RESULTS: no randomised controlled trials were found. The review details reported
      use of tourniquets in arterial reconstruction, including techniques, outcomes and
      potential complications. CONCLUSION: the use of a tourniquet is a safe and
      effective technique to facilitate arterial reconstruction.

PMID- 10942683
TI  - Vascular and stromal features in the skin of the lower limb in patients with
      chronic critical limb ischaemia (CLI) and oedema.
AB  - OBJECTIVE: peripheral oedema is often observed in limbs affected by chronic
      critical limb ischaemia (CLI) and is mainly subcutaneous in distribution.
      Previous work has shown that capillary filtration coefficient (CFC) in limbs with
      CLI and oedema was twice as great as that in the contralateral limb. These
      changes might be due to morphological changes. Transmission electron microscopy
      (TEM) was used to examine the morphological features of the capillary walls and
      surrounding stromal tissues in the skin of these limbs. MATERIAL AND METHODS:
      eight patients with unilateral CLI and peripheral pitting oedema (four men, four
      women, a mean age of 81+/-6.9 years) was studied. Skin biopsies were taken from
      the pulp of the first toe, interdigital space between the first and second digits
      and dorsal part of forefoot just prior to amputation. RESULTS: stromal oedema and
      dilated capillaries were most prominent in the distal part of the foot. Some of
      the capillaries were filled with blood cells and some were empty. The endothelium
      of the dilated vessels was elongated and distended. In some patients a number of
      capillaries were collapsed with degenerate endothelial cells. <<<<Gaps>>>>, i.e.
      large openings, were found between the elongated oedematous endothelial cells.
      The basal lamina was thickened in all patients. Stromal haemorrhage and
      degeneration were seen in approximately 50% of patients. CONCLUSION: CLI causes
      ultrastructural changes in the capillary endothelium and surrounding stroma. The
      presence of large gaps between endothelial cells as well as an increased
      capillary pressure may enhance transcapillary transudation, and are most likely
      the causative factors in the formation of the ischaemic oedema. The stromal
      haemorrhage as well as degeneration probably signifies a terminal stage of CLI.

PMID- 10942684
TI  - Postoperative delirium in patients with chronic lower limb ischaemia: what are
      the specific markers?
AB  - OBJECTIVES: we determined the incidence and specific markers of postoperative
      delirium in elderly patients with chronic lower limb ischaemia. PATIENTS AND
      METHODS: since April, 1995, 110 patients aged 60 years or older (mean: 71.6+/-6.6
      years) who underwent bypass surgery were assessed regarding aetiological factors
      of delirium: age, sex, dementia, body-mass index, hypertension, diabetes,
      cerebral disease, laboratory test results, severity of limb ischaemia, type of
      arterial occlusion, operative time, and blood transfusion. RESULTS: discriminant
      analysis showed statistical significance in the following five variables: age
      >/=70 years; critical limb ischaemia (and/or ankle pressure <40 mmHg); dementia;
      duration of operation >/=7 hours; low serum albumin. The overall percentage of
      cases correctly classified was 78.2% (Wilks>> Lambda=0.695, p<0.001); the
      standardized regression coefficients of the five variables were 0.648, 0.500,
      0.329, 0.218, and 0.200, respectively. In logistic regression, the regression
      coefficients for old age and critical limb ischaemia were 2.646 (14.1 of odds
      ratio; 95% confidence interval, 2.7-72.0) and 1.337 (3.8; 1.3-10.9),
      respectively. CONCLUSIONS: the incidence of postoperative delirium in elderly
      patients with chronic lower-limb ischaemia was as high as 42.3%, and an age of
      over 70 years and critical limb ischaemia were identified as specific markers,
      with 14.1 times and 3.8 times the odds of suffering from delirium after bypass
      surgery.

PMID- 10942685
TI  - Expression of cyclo-oxygenase-2 in human atherosclerotic carotid arteries.
AB  - OBJECTIVES: the preventive effect of acetylsalicylic acid in cardiovascular
      disease may be due to inhibition of platelet aggregation mediated by COX-1, but
      may in addition be due to anti-inflammatory effects by inhibition of COX-2. The
      objective of this study was to analyse the expression of COX-1 and COX-2 in
      atherosclerotic and healthy vascular walls. DESIGN: the expression COX-1 and COX
      2 was analysed in biopsies from human atherosclerotic carotid arteries and from
      healthy mammary arteries and saphenous veins. MATERIALS: vascular biopsies were
      obtained from patients undergoing carotid endarterectomy or coronary bypass
      surgery. METHODS: RT-PCR was used for mRNA analysis and for localization of
      proteins we used immunohistochemistry. RESULTS: COX-2 was found in
      atherosclerotic plaques: in macrophages, in some smooth muscle cells and in
      endothelial cells of small vessels in the lesions. In non-atherosclerotic blood
      vessels, COX-2 was detected in the endothelium of the vasa vasorum in the
      adventitia. COX-1 was found in the endothelium in healthy and in atherosclerotic
      vessels. CONCLUSIONS: the expression of COX-2 by inflammatory and vascular cells
      in atherosclerotic arteries suggests that products of this enzyme may be
      important in the pathogenesis of atherosclerosis.

PMID- 10942686
TI  - Eversion carotid endarterectomy generates fewer microemboli than standard carotid
      endarterectomy.
AB  - OBJECTIVES: to test whether the occurrence of microembolism differed between
      eversion and standard carotid endarterectomy (CEA). DESIGN: prospective, non
      randomised transcranial Doppler (TCD) monitoring study of 61 patients. MATERIALS
      AND METHODS: eversion CEA was performed in 27 and standard CEA in 34 patients.
      Surgery was performed under general anaesthesia. Three (5%) patients had a shunt
      inserted based on continuous EEG monitoring. Continuous middle cerebral artery
      TCD monitoring (EME, TC-4040) was performed intraoperatively and for 45 min
      postoperatively on day 1, day 2-3, day 4-5 and after 3 months. Unidirectional
      signals lasting >25 ms, having intensities of >9 dB were considered to represent
      embolic events. RESULTS: intraoperative embolic events were detected in 50 (93%)
      of 54 patients in whom successful intraoperative TCD monitoring was achieved.
      Events occurred most frequently immediately following clamp release (85%),
      without difference between the two techniques. Embolic events were encountered
      postoperatively in four (15%) and 16 (48%) patients having eversion and standard
      CEA, respectively (p< 0.02). Four patients developed new neurological symptoms
      equally distributed between eversion and standard CEA. Two (3%) deficits were
      permanent and two transient. The patency of the carotid bifurcation was confirmed
      in all instances with duplex scanning. CONCLUSION: we identified a surprisingly
      high number of postoperative embolic events as detected with transcranial Doppler
      in patients who had undergone carotid surgery using standard endarterectomy, as
      compared to patients who underwent eversion endarterectomy. Whether this
      difference has any clinical implication has yet to be proved.

PMID- 10942687
TI  - Are we still performing inappropriate carotid endarterectomy?
AB  - OBJECTIVES: the 1998 ECST final report suggests that the decision to operate on
      patients with greater than 70% symptomatic stenosis should be based on a
      statistical model incorporating age, sex and degree of stenosis. The aim of this
      study was to identify patients operated on the basis of the 1991 reports who
      would not now be offered surgery according to the 1998 ECST recommendations and
      to determine the surgical morbidity and mortality arising from these
      <<<<inappropriate>>>> CEAs. METHODS: interrogation of a prospectively gathered
      database of all CEAs performed for symptomatic stenosis between 1st January 1994
      and 1st May 1998. CEAs were classified as <<<<beneficial>>>>, <<<<uncertain>>>>
      or <<<<hazardous>>>> according to the 1998 ECST recommendations. RESULTS: there
      were 154 males and 72 females (median age (range) was 67 (39-85) and 65 (38-81),
      respectively). In males 101 (66%) of CEAs were <<<<beneficial>>>>, 51 (33%) were
      <<<<uncertain>>>> and only two (1%) were <<<<hazardous>>>>. In women, the
      corresponding proportions were 13 (18%), 45 (63%) and 14 (19%), respectively. The
      combined peri-operative major stroke (Rankin 3-5) and death rate was 1.8% (4
      patients). Of these, three, one and zero patients were in the <<<<beneficial>>>>,
      <<<<uncertain>>>> and <<<<hazardous>>>> groups. CONCLUSIONS: strict adherence to
      the 1998 ECST recommendations would reduce by 50% the number of CEAs currently
      performed in this vascular unit and, in general, would restrict CEA to a higher
      risk group. The validity of the ECST model requires further evaluation.

PMID- 10942688
TI  - Outcome of acute renal failure following surgical repair of ruptured abdominal
      aortic aneurysms.
AB  - OBJECTIVES: to establish the mortality of ARF following surgical repair of
      ruptured abdominal aortic aneurysms (AAAs) and to identify clinical variables
      which might assist in predicting outcome. DESIGN, MATERIALS AND METHODS: all
      cases of ARF complicating repair of ruptured AAAs treated at Leicester General
      Hospital between 1984 and 1996 were identified in a retrospective study based on
      review of clinical records. The main outcome measures were overall mortality,
      duration of hospital treatment and renal function in survivors. RESULTS: in 65
      cases identified, overall hospital mortality was 75%. Six patients did not
      receive RRT, since their clinical state was judged irreversible; all died. Of the
      16 survivors, 11 were left with irreversible renal impairment and one patient
      required maintenance dialysis. Over half of the survivors had died at 5 years>>
      follow-up. Non-survivors had more vascular disease (p=0.048), required more
      surgery during AAA repair (p=0.042) and were more likely to have developed
      multiple organ failure (p=0.01). A clinical severity score based on these three
      variables allowed stratification into prognostic groups. CONCLUSIONS: ARF
      following surgical repair of ruptured AAA has an overall hospital mortality of
      75%. A clinical severity score, calculated at the time dialysis was considered,
      may assist in prediction of outcome.

PMID- 10942689
TI  - Interleukin-10 appearance following thoraco-abdominal and abdominal aortic
      aneurysm repair is associated with the duration of visceral ischaemia.
AB  - OBJECTIVES: to evaluate the plasma IL-10 levels during elective operative repair
      of thoraco-abdominal and abdominal aortic aneurysm repair. To study whether IL-10
      plasma levels are associated with the duration of cross-clamping (ischaemia) and
      clinical outcome. MATERIALS: fifteen consecutive patients undergoing surgery for
      TAAA and 10 consecutive patients undergoing surgical repair of AAA were included.
      METHODS: plasma concentrations of IL-10 were measured by ELISA technique.
      Clinical outcome of the TAAA patients was prospectively analysed. RESULTS: during
      aortic clamping IL-10 was produced in both populations. The plasma IL-10 peak
      (934+/-172 pg/ml) of the TAAA group was seen at 4 h after declamping and remained
      detectable after 48 h. The plasma IL-10 peak (212+/-32 pg/ml) of the AAA group
      was seen 30 min after declamping and fell to undetectable levels by 24 h. These
      data show that the peak IL-10 plasma levels in TAAA repair are significantly
      (p<0.05) higher compared to the peak IL-10 plasma levels as seen during AAA
      repair. A positive correlation was seen between cross-clamping and peak plasma IL
      10 and organ dysfunction. CONCLUSIONS: IL-10 plasma concentrations appear higher,
      later and are longer detectable in patients undergoing TAAA. Correlations were
      seen with duration of cross-clamping and MSOD.

PMID- 10942690
TI  - Are there seasonal patterns to ruptured aortic aneurysms and dissections of the
      aorta?
AB  - OBJECTIVE: to test the hypothesis that there are seasonal increases in aortic
      aneurysm ruptures and dissections. METHODS: a retrospective, population-based
      time series analysis of hospital admissions for dissection and rupture of the
      aortic aneurysm in the Province of Ontario from 1988-1997. Analyses were carried
      out on weekly and monthly aggregations of hospital admissions. RESULTS: there is
      weak statistical evidence of seasonality in the weekly time series (BKS=0.0987,
      p=0.03) and no evidence of seasonality in the monthly time series. There is no
      evident seasonality in the time plots. The incidence of dissections increased
      significantly over the study period while the incidence of ruptures decreased.
      CONCLUSIONS: this large population-based study, contrary to other published
      reports, fails to find convincing evidence of seasonality in rupture or
      dissection of aortic aneurysm though did demonstrate contrasting trends in
      incidence.

PMID- 10942691
TI  - Maximal aneurysm diameter follow-up is inadequate after endovascular abdominal
      aortic aneurysm repair.
AB  - BACKGROUND: follow-up after endovascular abdominal aortic aneurysm repair (EAR)
      generally consists of serial diameter measurements. A size change after EAR,
      however, is the consequence of alterations of the excluded aneurysm sac volume.
      OBJECTIVE: to assess the agreement between diameter measurements and volume
      measurements after endovascular aneurysm repair. PATIENTS AND METHODS: from 53
      consecutive patients scheduled for EAR, follow-up of at least 6 months was
      available in 35 patients. CTA was performed on all patients at discharge, at 6
      months and yearly thereafter. The resulting 113 datasets were processed on a
      workstation in a blinded and random order. Maximal aneurysm diameter (DMAX) was
      measured along the central lumen line. Total aneurysm volume was measured by
      manual segmentation. All measurements of an individual patient were compared with
      each other, resulting in 149 comparisons. The significance of individual size
      changes was classified based on the 95% confidence limits of the intra-observer
      variability, using difference-of-means analysis. DMAX changes were compared to
      volume changes. RESULTS: in 37% of the comparisons, discordance was found between
      DMAX and volume measurements. A decrease in aneurysm size was missed using DMAX
      in 14% of cases and an increase in 19% of cases. CONCLUSION: aneurysm size
      changes after EAR are not noticed using maximal diameter measurements in over one
      third of cases.

PMID- 10942692
TI  - The impact of stent design on proximal stent-graft fixation in the abdominal
      aorta: an experimental study.
AB  - OBJECTIVE: to study the proximal fixation of different aortic stent grafts in
      comparison to a hand-sewn anastomosis. DESIGN: experimental study. MATERIAL: the
      infrarenal aorta of 16 human cadavers were exposed, left in situ and transected 3
      cm above the aortic bifurcation to mimic an infrarenal aortic neck. Stent grafts
      were deployed through a sheath 5 cm into the aorta. Ancure, Talent, Vanguard,
      Zenith and a Palmaz based stent graft were assessed. In addition a polyester
      graft was anastomosed to the aorta by running sutures. Distal force was applied
      to the grafts in increments of 0.5 Newton until the stent grafts were completely
      dislodged from the aorta. The displacement force (DF) was thereby determined.
      RESULTS: a force of 150 N (140-160) applied to the hand-sewn graft resulted in
      tearing of the aorta, without breakage of the sutures. The median displacement
      force was for Talent 4.5 N (1.3-5.5), Vanguard 9.0 N (3. 5-12), Ancure 12.5 N (12
      14), Zenith 24 N (23-26.5) and Palmaz 25 N (17-25). Ballooning the stent after
      deployment improved fixation in some cases. CONCLUSIONS: a sutured anastomosis
      fixates a graft better than any stent design tested. Hooks and barbs improve the
      fixation of self-expandable stents. Balloon dilatation of the proximal stent
      after deployment might increase fixation further. Balloon expandable stents seem
      to provide good fixation without the use of hooks and barbs.

PMID- 10942693
TI  - Intermittent groin swelling following a polytetrafluoroethylene iliofemoral
      graft.

PMID- 10942694
TI  - Aneurysm of the middle colic artery--case report and literature review.

PMID- 10942695
TI  - Severe hypertension and childhood epilepsy in a 23-year-old Caucasian woman.

PMID- 10942696
TI  - A life-threatening case of a left upper quadrant mass.

PMID- 10942697
TI  - Relief of leg ischaemia by caesarean section: a case report of aortic dissection
      during pregnancy.

PMID- 10942698
TI  - Infectious aneurysm formation after depot acupuncture.

PMID- 10942699
TI  - Diminished epiphyseal growth following iatrogenic vascular trauma.

PMID- 10942700
TI  - Abnormal intracellular ca(2+)homeostasis and disease.
AB  - A whole range of cell functions are regulated by the free cytosolic
      Ca(2+)concentration. Activator Ca(2+)from the extracellular space enters the cell
      through various types of Ca(2+)channels and sometimes the Na(+)/Ca(2+)-exchanger,
      and is actively extruded from the cell by Ca(2+)pumps and Na(+)/Ca(2+)
      exchangers. Activator Ca(2+)can also be released from internal Ca(2+)stores
      through inositol trisphosphate or ryanodine receptors and is taken up into these
      organelles by means of Ca(2+)pumps. The resulting Ca(2+)signal is highly
      organized in space, frequency and amplitude because the localization and the
      integrated free cytosolic Ca(2+)concentration over time contain specific
      information. Mutations or functional abnormalities in the various
      Ca(2+)transporters, which in vitro seem to induce trivial functional alterations,
      therefore, often lead to a plethora of diseases. Skeletal-muscle pathology can be
      caused by mutations in ryanodine receptors (malignant hyperthermia, porcine
      stress syndrome, central-core disease), dihydropyridine receptors (familial
      hypokalemic periodic paralysis, malignant hyperthermia, muscular dysgenesis) or
      Ca(2+)pumps (Brody disease). Ca(2+)-pump mutations in cutaneous epidermal
      keratinocytes and cochlear hair cells lead to, skin diseases (Darier and Hailey
      Hailey) and hearing/vestibular problems respectively. Mutated Ca(2+)channels in
      the photoreceptor plasma membrane cause vision problems. Hemiplegic migraine,
      spinocerebellar ataxia type-6, one form of episodic ataxia and some forms of
      epilepsy can be due to mutations in plasma-membrane Ca(2+)channels, while
      antibodies against these channels play a pathogenic role in all patients with the
      Lambert-Eaton myasthenic syndrome and may be of significance in sporadic
      amyotrophic lateral sclerosis. Brain inositol trisphosphate receptors have been
      hypothesized to contribute to the pathology in opisthotonos mice, manic
      depressive illness and perhaps Alzheimer's disease. Various abnormalities in
      Ca(2+)-handling proteins have been described in heart during aging, hypertrophy,
      heart failure and during treatment with immunosuppressive drugs and in diabetes
      mellitus. In some instances, disease-causing mutations or abnormalities provide
      us with new insights into the cell biology of the various Ca(2+)transporters.

PMID- 10942701
TI  - Use of co-loaded Fluo-3 and Fura Red fluorescent indicators for studying the
      cytosolic Ca(2+)concentrations distribution in living plant tissue.
AB  - A method for visualisation of cytosolic [Ca(2+)] distribution was applied to
      living plant tissue. A mixture of the fluorescent probes Fluo-3 and Fura Red was
      used. The emitted fluorescence was scanned simultaneously in two channels with a
      laser-scanning confocal microscope and rationing was performed. The homogeneity
      of the Fluo-3/Fura Red concentration ratio throughout the tissue after AM-ester
      loading was proven. In vitro calibration permitted conversion of Fluo-3/Fura Red
      fluorescence ratios to [Ca(2+)] values. Apparent K(D)of 286 nM, R(min)of 0.43 and
      R(max)of 18 were calculated. The in vivo determination of extreme ratio values
      was performed by permeabilizing the plasmalemma for Ca(2+)with a ionophore and
      manipulating the extracellular [Ca(2+)]. The resultant R(minv)of 1.33 and
      R(maxv)of 2.69 for vegetative apices, and R(mini)of 1.26 and R(maxi)of 3.45 for
      apices induced to flowering, suggested incomplete equalization of extra- and
      intracellular Ca(2+)levels in these experiments. In Chenopodium rubrum, the
      cytosolic [Ca(2+)] patterns of apical tissue obtained using Fluo-3 and Fura Red
      were significantly different between vegetative apices and apices after
      photoperiodic flower induction. This methodological approach may also be helpful
      for studying cytosolic [Ca(2+)] distribution in other living plant tissues.

PMID- 10942702
TI  - Calmodulin regulates the disassembly of cortical F-actin in mast cells but is not
      required for secretion.
AB  - Secretion is dependent on a rise in cytosolic Ca(2+)concentration and is
      associated with dramatic changes in actin organization. The actin cortex may act
      as a barrier between secretory vesicles and plasma membrane. Thus, disassembly of
      this cortex should precede late steps of exocytosis. Here we investigate
      regulation of both the actin cytoskeleton and secretion by calmodulin. Ca(2+),
      together with ATP, induces cortical F-actin disassembly in permeabilized rat
      peritoneal mast cells. This effect is strongly inhibited by removing endogenous
      calmodulin (using calmodulin inhibitory peptides), and increased by exogenous
      calmodulin. Neither treatment, however, affects secretion. Low concentrations (
      approximately 1 microM) of a specific inhibitor of myosin light chain kinase, ML
      7, prevent F-actin disassembly, but not secretion. In contrast, a myosin
      inhibitor affecting both conventional and unconventional myosins, BDM, decreases
      cortical disassembly as well as secretion. Observations of fluorescein
      calmodulin, introduced into permeabilized cells, confirmed a strong (Ca(2+)
      independent) association of calmodulin with the actin cortex. In addition,
      fluorescein-calmodulin enters the nuclei in a Ca(2+)-dependent manner. In
      conclusion, calmodulin promotes myosin II-based contraction of the membrane
      cytoskeleton, which is a prerequisite for its disassembly. The late steps of
      exocytosis, however, require neither calmodulin nor cortical F-actin disassembly,
      but may be modulated by unconventional myosin(s).

PMID- 10942703
TI  - Regulation of fertilization-induced Ca(2+)spiking in the mouse zygote.
AB  - Fertilization-induced Ca(2+)spiking in mouse zygotes ceases at the end of pre-G1
      as pronuclei (PN) form. In the present studies we found that there was no
      consistent temporal relationship between PN formation and cessation of spiking.
      We also show that nucleate and anucleate fragments of zygotes, obtained by
      bisection of fertilized eggs prior to PN formation, both ceased spiking at times
      that did not depend on the presence of the PN. We, therefore, concluded that
      formation of the PN does not cause spiking cessation. The possibility that
      cessation of the fertilization-induced Ca(2+)spiking may be mediated by a redox
      sensitive mechanism affecting the sensitivity of Ca(2+)release from internal
      stores is proposed. At first mitosis, a small proportion of zygotes show low
      amplitude calcium spikes prior to pronuclear envelope breakdown (PNEBD), whereas
      all zygotes spiked at this time in the presence of high extracellular Ca(2+)and
      dithiothreitol. Nucleated zygotic fragments also spiked before PNEBD whereas
      anucleated ones rarely did. Exit from G2 was required for this spiking to be
      observed in nucleated zygotes or fragments. Arrest in M-phase resulted in the
      appearance of a prolonged series of small amplitude spikes. It is concluded that
      the spiking at mitosis is cell cycle regulated and may differ qualitatively in
      its control from that at fertilization.

PMID- 10942704
TI  - Endothelin-stimulated Ca(2+)signaling and endothelin receptor expression are
      decreased by parathyroid hormone treatment in UMR-106 osteoblastic osteosarcoma
      cells.
AB  - Modulation of endothelin (ET-1)-induced [Ca(2+)](i)transients and receptor
      expression by parathyroid hormone (PTH) was studied in UMR-106 osteoblastic
      osteosarcoma cells. Ca(2+)signaling was assessed with Fura-2, and ET receptor
      mRNA expression was determined using ET(A)- and ET(B)-specific primers and RT-PCR
      amplification. ET-1 binding in UMR-106 cell membranes was also measured. PTH
      pretreatment for 8 h decreased the [Ca(2+)](i)transients elicited by ET-1 and by
      the ET(B)-selective agonist sarafotoxin 6c (S6c). When ET(B)receptors were
      desensitized by pretreatment with S6c or blocked with the ET(B)-selective
      antagonist BQ-788, the remaining ET(A)component of the signal was also decreased
      by PTH pretreatment. In contrast, [Ca(2+)](i)transients elicited by
      PGF(2alpha)and ionomycin were increased following PTH pretreatment, indicating
      that the effect of PTH to decrease ET-1-stimulated transients was selective. PTH
      pretreatment also decreased [(125)I]ET-1 binding and ET(A)and ET(B)mRNA, with
      maximal effects at approximately 8 h. ET-1 was not detectable in medium from
      either control or PTH treated UMR-106 cultures, suggesting that the decreased
      expression of ET receptors was not due to enhanced ET production and subsequent
      homologous desensitization. The downregulation of ET receptors in osteoblasts by
      PTH pretreatment may serve as a homeostatic mechanism in bone.

PMID- 10942705
TI  - Mechanisms of sodium pump regulation.
AB  - The Na(+)-K(+)-ATPase, or sodium pump, is the membrane-bound enzyme that
      maintains the Na(+) and K(+) gradients across the plasma membrane of animal
      cells. Because of its importance in many basic and specialized cellular
      functions, this enzyme must be able to adapt to changing cellular and
      physiological stimuli. This review presents an overview of the many mechanisms in
      place to regulate sodium pump activity in a tissue-specific manner. These
      mechanisms include regulation by substrates, membrane-associated components such
      as cytoskeletal elements and the gamma-subunit, and circulating endogenous
      inhibitors as well as a variety of hormones, including corticosteroids, peptide
      hormones, and catecholamines. In addition, the review considers the effects of a
      range of specific intracellular signaling pathways involved in the regulation of
      pump activity and subcellular distribution, with particular consideration given
      to the effects of protein kinases and phosphatases.

PMID- 10942706
TI  - Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl(-)/HCO(3)(-) secretion in T84
      cells in vitro.
AB  - ACE, accessory cholera enterotoxin, the third enterotoxin in Vibrio cholerae, has
      been reported to increase short-circuit current (I(sc)) in rabbit ileum and to
      cause fluid secretion in ligated rabbit ileal loops. We studied the ACE-induced
      change in I(sc) and potential difference (PD) in T84 monolayers mounted in
      modified Ussing chambers, an in vitro model of a Cl(-) secretory cell. ACE added
      to the apical surface alone stimulated a rapid increase in I(sc) and PD that was
      concentration dependent and immediately reversed when the toxin was removed. Ion
      replacement studies established that the current was dependent on Cl(-) and
      HCO(3)(-). ACE acted synergistically with the Ca(2+)-dependent acetylcholine
      analog, carbachol, to stimulate secretion in T84 monolayers. In contrast, the
      secretory response to cAMP or cGMP agonists was not enhanced by ACE. The ACE
      stimulated secretion was dependent on extracellular and intracellular Ca(2+) but
      was not associated with an increase in intracellular cyclic nucleotides. We
      conclude that the mechanism of secretion by ACE involves Ca(2+) as a second
      messenger and that this toxin stimulates a novel Ca(2+)-dependent synergy.

PMID- 10942707
TI  - Selective mobilization of CD14(+)CD16(+) monocytes by exercise.
AB  - Strenuous, anaerobic exercise leads to an increase of leukocytes that are
      mobilized from the marginal pool. We have analyzed in human peripheral blood the
      effect of exercise on the number of CD14(+)CD16(+) monocytes as determined by two
      color immunofluorescence and flow cytometry. We show herein that this type of
      monocyte responds with a dramatic up to 4.8-fold increase. Mobilization does not
      occur after 1 min at 100 or 200 W but 1 min at 400 W leads to a twofold increase
      of the CD14(+)CD16(+) monocytes immediately after exercise. The numbers remain
      high at 5 min and gradually decrease to reach the initial level at 20 min
      postexercise. After 20 min of rest, the CD14(+)CD16(+) monocytes can be mobilized
      again by a second exercise. The CD14(+)CD16(+) monocytes appear to be mobilized
      from the marginal pool where they preferentially home because of a higher
      expression of adhesion molecules like CD11d and very late antigen-4. Exercise
      goes along with an increase of catecholamines, and mobilization of the
      CD14(+)CD16(+) monocytes can be substantially reduced by treatment of donors with
      the beta-adrenergic receptor blocker propranolol. Mobilization of CD14(+)CD16(+)
      monocytes by a catecholamine-dependent mechanism may contribute to the increase
      of these cells in various clinical conditions.

PMID- 10942708
TI  - Acute glucose-induced downregulation of PKC-betaII accelerates cultured VSMC
      proliferation.
AB  - Accelerated vascular smooth muscle cell (VSMC) proliferation contributes to the
      formation of atherosclerotic lesions. To investigate protein kinase C (PKC)
      betaII functions with regard to glucose-induced VSMC proliferation, human VSMC
      from aorta (AoSMC), a clonal VSMC line of rat aorta (A10), and A10 cells
      overexpressing PKC-betaI (betaI-A10) and PKC-betaII (betaII-A10) were studied
      with the use of three techniques to evaluate glucose effects on aspects affecting
      proliferation. High glucose (25 mM) increased DNA synthesis and accelerated cell
      proliferation compared with normal glucose (5.5 mM) in AoSMC and A10 cells, but
      not in betaI-A10 and betaII-A10 cells. The PKC-betaII specific inhibitor CGP
      53353 inhibited glucose-induced cell proliferation and DNA synthesis in AoSMC and
      A10 cells. In flow cytometry analysis, high glucose increased the percentage of
      A10 cells at 12 h after cell cycle initiation but did not increase the percentage
      of betaI-A10 or betaII-A10 cells entering S phase. PKC-betaII protein levels
      decreased before the peak of DNA synthesis, and high glucose further decreased
      PKC-betaII mRNA and protein levels in AoSMC and A10 cells. These results suggest
      that high glucose downregulates endogenous PKC-betaII, which then alters the
      normal inhibitory role of PKC-betaII in cell cycle progression, resulting in the
      stimulation of VSMC proliferation through acceleration of the cell cycle.

PMID- 10942709
TI  - Connexin46 mutations linked to congenital cataract show loss of gap junction
      channel function.
AB  - Human connexin46 (hCx46) forms gap junctional channels interconnecting lens fiber
      cells and appears to be critical for normal lens function, because hCx46
      mutations have been linked to congenital cataracts. We studied two hCx46 mutants,
      N63S, a missense mutation in the first extracellular domain, and fs380, a frame
      shift mutation that shifts the translational reading frame at amino acid residue
      380. We expressed wild-type Cx46 and the two mutants in Xenopus oocytes.
      Production of the expressed proteins was verified by SDS-PAGE after metabolic
      labeling with [(35)S]methionine or by immunoblotting. Dual two-microelectrode
      voltage-clamp studies showed that hCx46 formed both gap junctional channels in
      paired Xenopus oocytes and hemi-gap junctional channels in single oocytes. In
      contrast, neither of the two cataract-associated hCx46 mutants could form
      intercellular channels in paired Xenopus oocytes. The hCx46 mutants were also
      impaired in their ability to form hemi-gap-junctional channels. When N63S or
      fs380 was coexpressed with wild-type connexins, both mutations acted like "loss
      of function" rather than "dominant negative" mutations, because they did not
      affect the gap junctional conductance induced by either wild-type hCx46 or wild
      type hCx50.

PMID- 10942710
TI  - Two distinct inactivation processes related to phosphorylation in cardiac L-type
      Ca(2+) channel currents.
AB  - We investigated the inactivation process of macroscopic cardiac L-type Ca(2+)
      channel currents using the whole cell patch-clamp technique with Na(+) as the
      current carrier. The inactivation process of the inward currents carried by Na(+)
      through the channel consisted of two components >0 mV. The time constant of the
      faster inactivating component (30.6 +/- 2.2 ms at 0 mV) decreased with
      depolarization, but the time constant of the slower inactivating component (489
      +/- 21 ms at 0 mV) was not significantly influenced by the membrane potential.
      The inactivation process in the presence of isoproterenol (100 nM) consisted of a
      single component (538 +/- 60 ms at 0 mV). A protein kinase inhibitor, H-89,
      decreased the currents and attenuated the effects of isoproterenol. In the
      presence of cAMP (500 microM), the inactivation process consisted of a single
      slow component. We propose that the faster inactivating component represents a
      kinetic of the dephosphorylated or partially phosphorylated channel, and
      phosphorylation converts the kinetics into one with a different voltage
      dependency.

PMID- 10942711
TI  - Skeletal muscle fiber quality in older men and women.
AB  - Whole muscle strength and cross-sectional area (WMCSA), and contractile
      properties of chemically skinned segments from single fibers of the quadriceps
      were studied in 7 young men (YM, 36.5 +/- 3. 0 yr), 12 older men (OM, 74.4 +/-
      5.9 yr), and 12 older women (OW, 72.1 +/- 4.3 yr). WMCSA was smaller in OM
      compared with YM (56.1 +/- 10.1 vs. 79.7 +/- 13.1 cm(2); P = 0.031) and in OW
      (44.9 +/- 7.5; P < 0.003) compared with OM. Age-related, but not sex-related,
      differences in strength were eliminated after adjusting for WMCSA. Maximal force
      was measured in 552 type I and 230 type IIA fibers. Fibers from YM (type I = 725
      +/- 221; type IIA = 792 +/- 271 microN) were stronger (P < 0.001) than fibers
      from OM (I = 505 +/- 179; IIA = 577 +/- 262 microN) even after correcting for
      size. Type IIA fibers were stronger (P < 0.005) than type I fibers in YM and OM
      but not in OW (I = 472 +/- 154; IIA = 422 +/- 97 microN). Sex-related differences
      in type I and IIA fibers were dependent on fiber size. In conclusion, differences
      in WMCSA explain age-related differences in strength. An intrinsic defect in
      contractile proteins could explain weakness in single fibers from OM. Sex-related
      differences exist at the whole muscle and single fiber levels.

PMID- 10942712
TI  - Hypertonic inhibition of exocytosis in neutrophils: central role for osmotic
      actin skeleton remodeling.
AB  - Hypertonicity suppresses neutrophil functions by unknown mechanisms. We
      investigated whether osmotically induced cytoskeletal changes might be related to
      the hypertonic inhibition of exocytosis. Hyperosmolarity abrogated the
      mobilization of all four granule types induced by diverse stimuli, suggesting
      that it blocks the process of exocytosis itself rather than individual signaling
      pathways. Concomitantly, osmotic stress provoked a twofold increase in F-actin,
      induced the formation of a submembranous F-actin ring, and abolished
      depolymerization that normally follows agonist-induced actin assembly. Several
      observations suggest a causal relationship between actin polymerization and
      inhibition of exocytosis: 1) prestimulus actin levels were inversely proportional
      to the stimulus-induced degranulation, 2) latrunculin B (LB) prevented the
      osmotic actin response and restored exocytosis, and 3) actin polymerization
      induced by jasplakinolide inhibited exocytosis under isotonic conditions. The
      shrinkage-induced tyrosine phosphorylation and the activation of the Na(+)/H(+)
      exchanger were not affected by LB. Inhibition of osmosensitive kinases failed to
      prevent the F-actin change, suggesting that the osmotic tyrosine phosphorylation
      and actin polymerization are independent phenomena. Thus cytoskeletal remodeling
      appears to be a key component in the neutrophil-suppressive, anti-inflammatory
      effects of hypertonicity.

PMID- 10942713
TI  - Potassium channels in basolateral membrane vesicles from necturus enterocytes:
      stretch and ATP sensitivity.
AB  - We have previously reported that ATP-inhibitable K(+) channels, in vesicles
      derived from the basolateral membrane of Necturus maculosus small intestinal
      cells, exhibit volume regulatory responses that resemble those found in the
      intact tissue after exposure to anisotonic solutions. We now report that
      increases in K(+) channel activity can also be elicited by exposure of these
      vesicles to isotonic solutions containing glucose or alanine that equilibrate
      across these membranes. We also demonstrate that swelling after exposure to a
      hypotonic solution or an isotonic solution containing alanine or glucose reduces
      inhibition of channel activity by ATP and that this finding cannot be simply
      attributed to dilution of intravesicular ATP. We conclude that ATP-sensitive,
      stretch-activated K(+) channels may be responsible for the well-established
      increase in basolateral membrane K(+) conductance of Necturus small intestinal
      cells after the addition of sugars or amino acids to the solution perfusing the
      mucosal surface, and we propose that increases in cell volume, resulting in
      membrane stretch, decreases the sensitivity of these channels to ATP.

PMID- 10942714
TI  - Calpain activity in fast, slow, transforming, and regenerating skeletal muscles
      of rat.
AB  - Fiber-type transitions in adult skeletal muscle induced by chronic low-frequency
      stimulation (CLFS) encompass coordinated exchanges of myofibrillar protein
      isoforms. CLFS-induced elevations in cytosolic Ca(2+) could activate proteases,
      especially calpains, the major Ca(2+)-regulated cytosolic proteases. Calpain
      activity determined by a fluorogenic substrate in the presence of unaltered
      endogenous calpastatin activities increased twofold in low-frequency-stimulated
      extensor digitorum longus (EDL) muscle, reaching a level intermediate between
      normal fast- and slow-twitch muscles. micro- and m-calpains were delineated by a
      calpain-specific zymographical assay that assessed total activities independent
      of calpastatin and distinguished between native and processed calpains. Contrary
      to normal EDL, structure-bound, namely myofibrillar and microsomal calpains, were
      abundant in soleus muscle. However, the fast-to-slow conversion of EDL was
      accompanied by an early translocation of cytosolic micro-calpain, suggesting that
      myofibrillar and microsomal micro-calpain was responsible for the twofold
      increase in activity and thus involved in controlled proteolysis during fiber
      transformation. This is in contrast to muscle regeneration where m-calpain
      translocation predominated. Taken together, we suggest that translocation is an
      important step in the control of calpain activity in skeletal muscle in vivo.

PMID- 10942715
TI  - Properties and submitochondrial localization of pig and rat renal phosphate
      activated glutaminase.
AB  - Two pools of phosphate-activated glutaminase (PAG) were separated from pig and
      rat renal mitochondria. The partition of enzyme activity corresponded with that
      of the immunoreactivity and also with the postembedding immunogold labeling of
      PAG, which was associated partly with the inner membrane and partly with the
      matrix. The outer membrane was not labeled. PAG in intact mitochondria showed
      enzymatic characteristics that were similar to that of the membrane fraction and
      also mimicked that of the polymerized form of purified pig renal PAG. PAG in the
      soluble fraction showed properties similar to that of the monomeric form of
      purified enzyme. It is indicated that the pool of PAG localized inside the inner
      mitochondrial membrane is dormant due to the presence of high concentrations of
      the inhibitor glutamate. Thus the enzymatically active PAG is assumed to be
      localized on the outer face of the inner mitochondrial membrane. The activity of
      this pool of PAG appears to be regulated by compounds in the cytosol, of which
      glutamate may be most important.

PMID- 10942716
TI  - Functional cross talk after activation of P2 and P1 receptors in oviductal
      ciliated cells.
AB  - The presence of ATP and adenosine receptors and their role in controlling ciliary
      activity in oviductal ciliated cells was studied by measuring the ciliary beat
      frequency (CBF) in oviductal tissue cultures. ATP, adenosine, and related
      compounds increased the CBF in a dose-dependent manner. We established that P2
      receptors of subtype 2Y(2) and P1 receptors of subtype A(2a) mediated the
      responses to ATP and adenosine, respectively. We found evidence to suggest that
      stimulation of ciliary activity by ATP requires D-myo-inositol 1,4, 5
      trisphosphate [Ins(1,4,5)P(3)] metabolism, intracellular Ca(2+) mobilization, and
      protein kinase C activation. On the other hand, the adenosine effect is mediated
      by activation of a G(s) protein-dependent pathway that enhances cAMP
      intracellular levels. To study the interaction between P2 and P1 receptors, cells
      were stimulated simultaneously with both agonists. We observed a synergistic
      increase of the CBF even at agonist concentrations (100 nM) that did not produce
      a significant response when added separately to the culture. Furthermore, a
      blocker of the cAMP pathway produced a reduction of the ATP response, whereas a
      blocker of the Ins(1,4,5)P(3) pathway also produced an inhibition of the
      adenosine response. Our evidence demonstrates that both ATP and adenosine
      receptors are present in a single ciliated cell and that a mechanism of cross
      talk could operate in the transduction pathways to control ciliary activity.

PMID- 10942717
TI  - Multilocular fat cells in WAT of CL-316243-treated rats derive directly from
      white adipocytes.
AB  - Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT)
      of rats treated with the beta3-adrenoceptor agonist, CL-316243 (CL). Objectives
      were to determine whether these multilocular adipocytes derived from cells that
      already existed in the WAT or from proliferation of precursor cells and whether
      new mitochondria contained in them were typical brown adipocyte mitochondria. Use
      of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL
      treatment showed that most multilocular cells derived from cells already present
      in the WAT. Morphological techniques showed that at least a subpopulation of
      unilocular adipocytes underwent conversion to multilocular mitochondria-rich
      adipocytes. A small proportion of multilocular adipocytes ( approximately 8%) was
      positive for UCP1 by immunohistochemistry. Biochemical techniques showed that
      mitochondrial protein recovered from WAT increased 10-fold and protein isolated
      from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a
      different protein composition of new mitochondria isolated from WAT from that of
      mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT
      to contain both UCP1, but at a much lower concentration than in BAT mitochondria,
      and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize
      that multilocular adipocytes present at 7 days of CL treatment have two origins.
      First, most come from convertible unilocular adipocytes that become multilocular
      and make many mitochondria that contain UCP3. Second, some come from a cell that
      gives rise to more typical brown adipocytes that express UCP1.

PMID- 10942718
TI  - Satellite cell proliferation in low frequency-stimulated fast muscle of
      hypothyroid rat.
AB  - Satellite cell proliferation was assessed in low-frequency-stimulated hypothyroid
      rat fast-twitch muscle by 5-bromo-2'-deoxyuridine (BrdU) labeling and subsequent
      staining of labeled muscle nuclei, and by staining for proliferating cell nuclear
      antigen (PCNA). BrdU labeling and PCNA staining were highly correlated and
      increased approximately fourfold at 5 days of stimulation, decayed thereafter,
      but remained elevated over control in 10- and 20-day stimulated muscles. Myogenin
      mRNA was approximately 4-fold elevated at 5 days and 1.5-fold at 10 days.
      Staining for myogenin protein yielded results similar to that for PCNA and BrdU.
      Furthermore, a detailed examination of the pattern of myogenin staining revealed
      that the number of myogenin-positive nuclei was elevated in the fast pure IIB
      fiber population at 5 and 10 days of chronic low-frequency stimulation. By 20
      days, myogenin staining was observed in transforming fast fibers that coexpressed
      embryonic and adult myosin heavy chain isoforms. In the slower fiber populations
      (i.e., IIA and I), myogenin-positive transforming fibers that coexpressed
      embryonic myosin heavy chain, appeared already at 5 days. Thus the satellite cell
      progeny on slower fibers seemed to proliferate less and to fuse earlier to their
      associated fibers than the satellite cell progeny on fast fibers. We suggest that
      the increase in muscle nuclei of the fast fibers might be a prerequisite for fast
      to-slow fiber type transitions.

PMID- 10942719
TI  - Regulation of secretion of PTHrP by Ca(2+)-sensing receptor in human astrocytes,
      astrocytomas, and meningiomas.
AB  - Parathyroid hormone-related protein (PTHrP) is the major mediator of the humoral
      hypercalcemia of malignancy and of malignant osteolysis associated with skeletal
      metastases of common epithelial cancers. PTHrP secretion is regulated by the
      extracellular calcium concentration ([Ca(2+)](o)) in several types of normal and
      malignant cells. Because the [Ca(2+)](o)-sensing receptor (CaR) is a key mediator
      of [Ca(2+)](o)-regulated hormone secretion [e.g., of parathyroid hormone (PTH) by
      parathyroid chief cells], we investigated the expression of the CaR and PTHrP in
      normal and neoplastic glial cells and studied the effects of [Ca(2+)](o) on PTHrP
      secretion. Our results show that primary embryonic human astrocytes (HPA) express
      CaR mRNA and protein as detected by RT-PCR and Western analysis, respectively.
      Furthermore, astrocytomas and meningiomas also express the CaR at similar levels
      as assessed by RT-PCR and Northern and Western blot analyses. HPA and
      astrocytomas express transcripts encoding all three known isoforms of PTHrP
      [PTHrP(139), PTHrP(141), and PTHrP(173), comprising 139, 141, and 173 predicted
      amino acid residues, respectively] as assessed by RT-PCR, whereas meningiomas
      express only the first two of these. Finally, elevated levels of [Ca(2+)](o) and
      other polycationic CaR agonists dose dependently stimulate PTHrP secretion from
      HPA, astrocytomas, and meningiomas, although both basal and high [Ca(2+)](o)
      stimulated rates of PTHrP secretion are approximately 2. 5-fold higher in HPA
      than in the glial tumors studied here. Therefore, our results show that HPA,
      astrocytomas, and meningiomas express both the CaR and PTHrP and that CaR
      agonists stimulate PTHrP secretion.

PMID- 10942721
TI  - Impairment of NF-kappaB activation and modulation of gene expression by
      calpastatin.
AB  - To address the involvement of the calpain system in both basal and silica-induced
      nuclear factor (NF)-kappaB activation, several human bronchial epithelial cell
      lines were established in which an intracellular inhibitor of calpain,
      calpastatin, was stably expressed. Reduced basal and silica-induced inhibitor
      (IkappaBalpha) degradation and NF-kappaB activation were observed in cells stably
      overexpressing calpastatin. In addition, the cells in which calpain was
      constitutively inhibited by the overexpression of calpastatin exhibited a notable
      morphological change. Whereas empty vector-transfected cells displayed a
      morphology indistinguishable from that of parental cells, cells overexpressing
      calpastatin exhibited a mosaic morphological change with reduced formation of
      lamella 30 min after the cells were seeded. Genefilter microarray experiments, in
      which 3,965 human genes can be evaluated for their expression at the same time,
      showed that calpastatin downregulated genes encoding several membrane-associated
      proteins or nuclear proteins and upregulated genes of collagen alpha2, DAZ, and
      mitochondrial capsule selenoprotein. These results suggest that, in addition to
      their proteolytic activities on cytoskeletal proteins and other cellular
      regulatory proteins, calpain-calpastatin systems can also affect the expression
      levels of genes encoding structural or regulatory proteins.

PMID- 10942720
TI  - gp120-induced alterations of human astrocyte function: Na(+)/H(+) exchange, K(+)
      conductance, and glutamate flux.
AB  - Many human immunodeficiency virus (HIV)-infected patients suffer from impaired
      neurological function and dementia. This facet of the disease has been termed
      acquired immunodeficiency syndrome (AIDS)-associated dementia complex (ADC).
      Several cell types, including astrocytes and neurons, are not productively
      infected by virus but are involved in ADC pathophysiology. Previous studies of
      rat astrocytes showed that an HIV coat protein (gp120) accelerated astrocyte
      Na(+)/H(+) exchange and that the resultant intracellular alkalinization activated
      a pH-sensitive K(+) conductance. The present experiments were conducted to
      determine whether gp120 affected human astrocytes in the same fashion. It was
      found that primary human astrocytes express a pH-sensitive K(+) conductance that
      was activated on intracellular alkalinization. Also, gp120 treatment of whole
      cell clamped human astrocytes activated this conductance specifically.
      Furthermore, gp120 inhibited glutamate uptake by primary human astrocytes. These
      altered physiological processes could contribute to pathophysiological changes in
      HIV-infected brains. Because the gp120-induced cell physiological changes were
      partially inhibited by dimethylamiloride (an inhibitor of Na(+)/H(+) exchange),
      our findings suggest that modification of human astrocyte Na(+)/H(+) exchange
      activity may provide a means of addressing some of the neurological complications
      of HIV infection.

PMID- 10942723
TI  - Differential Ca(2+) sensitivity of skeletal and cardiac muscle ryanodine
      receptors in the presence of calmodulin.
AB  - Calmodulin (CaM) activates the skeletal muscle ryanodine receptor Ca(2+) release
      channel (RyR1) in the presence of nanomolar Ca(2+) concentrations. However, the
      role of CaM activation in the mechanisms that control Ca(2+) release from the
      sarcoplasmic reticulum (SR) in skeletal muscle and in the heart remains unclear.
      In media that contained 100 nM Ca(2+), the rate of (45)Ca(2+) release from
      porcine skeletal muscle SR vesicles was increased approximately threefold in the
      presence of CaM (1 microM). In contrast, cardiac SR vesicle (45)Ca(2+) release
      was unaffected by CaM, suggesting that CaM activated the skeletal RyR1 but not
      the cardiac RyR2 channel isoform. The activation of RyR1 by CaM was associated
      with an approximately sixfold increase in the Ca(2+) sensitivity of
      [(3)H]ryanodine binding to skeletal muscle SR, whereas the Ca(2+) sensitivity of
      cardiac SR [(3)H]ryanodine binding was similar in the absence and presence of
      CaM. Cross-linking experiments identified both RyR1 and RyR2 as predominant CaM
      binding proteins in skeletal and cardiac SR, respectively, and [(35)S]CaM binding
      determinations further indicated comparable CaM binding to the two isoforms in
      the presence of micromolar Ca(2+). In nanomolar Ca(2+), however, the affinity and
      stoichiometry of RyR2 [(35)S]CaM binding was reduced compared with that of RyR1.
      Together, our results indicate that CaM activates RyR1 by increasing the Ca(2+)
      sensitivity of the channel, and further suggest differences in CaM's functional
      interactions with the RyR1 and RyR2 isoforms that may potentially contribute to
      differences in the Ca(2+) dependence of channel activation in skeletal and
      cardiac muscle.

PMID- 10942722
TI  - ATP induces dephosphorylation of myosin light chain in endothelial cells.
AB  - In cultured porcine aortic endothelial monolayers, the effect of ATP on myosin
      light chain (MLC) phosphorylation, which controls the endothelial contractile
      machinery, was studied. ATP (10 microM) reduced MLC phosphorylation but increased
      cytosolic Ca(2+) concentration ([Ca(2+)](i)). Inhibition of the ATP-evoked
      [Ca(2+)](i) rise by xestospongin C (10 microM), an inhibitor of the inositol
      trisphosphate-dependent Ca(2+) release from endoplasmic reticulum, did not affect
      the ATP-induced dephosphorylation of MLC. MLC dephosphorylation was prevented in
      the presence of calyculin A (10 nM), an inhibitor of protein phosphatases PP-1
      and PP-2A. Thus ATP activates MLC dephosphorylation in a Ca(2+)-independent
      manner. In the presence of calyculin A, MLC phosphorylation was incremented after
      addition of ATP, an effect that could be abolished when cells were loaded with
      the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N, N,N',N'-tetraacetic acid
      acetoxymethyl ester (10 microM). Thus ATP also activates a Ca(2+)-dependent
      kinase acting on MLC. In summary, ATP simultaneously stimulates a functional
      antagonism toward both phosphorylation and dephosphorylation of MLC in which the
      dephosphorylation prevails. In endothelial cells, ATP is the first physiological
      mediator identified to activate MLC dephosphorylation by a Ca(2+)-independent
      mechanism.

PMID- 10942724
TI  - Multiple receptor activation elicits synergistic IP formation in nonpigmented
      ciliary body epithelial cells.
AB  - We have examined the interaction between muscarinic and alpha(2)-adrenergic
      receptor activation on inositol phosphate (IP) formation in the nonpigmented
      cells of the ciliary body epithelium (NPE cells) of the rabbit. We have compared
      these changes with those previously observed in the intracellular free Ca(2+)
      concentration. Whereas muscarinic receptor activation causes an increase in
      intracellular Ca(2+) and IP formation, activation of alpha(2)-receptors does not
      significantly increase either intracellular Ca(2+) or IPs over basal levels.
      However, simultaneous activation of muscarinic and alpha(2)-adrenergic receptors
      with the specific agonists carbachol and UK-14304 produces massive Ca(2+)
      increases and results in a synergistic increase in IP formation. This synergistic
      IP formation is inhibited by both muscarinic and alpha(2)-adrenergic receptor
      antagonists as well as by pertussis toxin and an inhibitor of phospholipase C. IP
      formation is predominantly independent of intracellular Ca(2+), because it is
      decreased but not prevented by blocking the entry of Ca(2+) with LaCl(3) or
      chelating intracellular Ca(2+) with 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid. Thus synergistic IP formation underlies, at least in part, the
      synergistic increase in intracellular Ca(2+) resulting from simultaneous
      activation of muscarinic and alpha(2)-adrenergic receptors.

PMID- 10942725
TI  - Differential regulation of tight junction permeability during development of the
      retinal pigment epithelium.
AB  - The retinal pigment epithelium (RPE) is an epithelial region of the blood-brain
      barrier. During embryogenesis, permeability of the barrier gradually decreases. A
      culture model of RPE development revealed differences in how tight junctions
      regulate the paracellular diffusion of ionic and nonionic solutes (Ban Y and
      Rizzolo LJ. Mol Vis 3: 18, 1997). To examine these differences, the permeation of
      ionic and nonionic monosaccharides was compared with mannitol, and the permeation
      of the alkali metals was compared with sodium. The order of permeation was 3-O
      methlyglucose = glucosamine = mannitol > N-acetylneuraminic acid. The ratio of N
      acetylneuraminic acid to mannitol permeability decreased with embryonic age of
      the RPE or exposure to retinal-conditioned medium. Neither the ratio nor the
      permeability was affected by inhibiting transcytosis. The ratio increased if
      tight junctions were disrupted in low-calcium medium. The permeation of cations
      followed the sequence cesium > rubidium > potassium = sodium > lithium and was
      unaffected by embryonic age or retinal-conditioned medium. These results are
      considered in terms of a model in which the size distribution, charge, or number
      of open junctional pores could be modulated. It suggests that different
      subpopulations of pores can be regulated independently during development.

PMID- 10942726
TI  - Differences in regulation of pH(i) in large (>/=10 nuclei) and small (</=5
      nuclei) osteoclasts.
AB  - Osteoclasts are multinucleated cells that resorb bone by extrusion of protons and
      proteolytic enzymes. They display marked heterogeneity in cell size, shape, and
      resorptive activity. Because high resorptive activity in vivo is associated with
      an increase in the average size of osteoclasts in areas of greater resorption and
      because of the importance of proton extrusion in resorption, we investigated
      whether the activity of the bafilomycin A(1)-sensitive vacuolar-type H(+)-ATPase
      (V-ATPase) and amiloride-sensitive Na(+)/H(+) exchanger differed between large
      and small osteoclasts. Osteoclasts were obtained from newborn rabbit bones,
      cultured on glass coverslips, and loaded with the pH-sensitive indicator 2', 7'
      bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Intracellular pH (pH(i)) was
      recorded in single osteoclasts by monitoring fluorescence. Large (>/=10 nuclei)
      and small (</=5 nuclei) osteoclasts differed in that large osteoclasts had a
      higher basal pH(i), their pH(i) was decreased by bafilomycin A(1) addition or
      removal of extracellular Na(+), and the realkalinization upon readdition of Na(+)
      was bafilomycin A(1) sensitive. After acid loading, a subpopulation of large
      osteoclasts (40%) recovered by V-ATPase activity alone, whereas all small
      osteoclasts recovered by Na(+)/H(+) exchanger activity. Interestingly, in 60% of
      the large osteoclasts, pH(i) recovery was mediated by both the Na(+)/H(+)
      exchanger and V-ATPase activity. Our results show a striking difference between
      pH(i) regulatory mechanisms of large and small osteoclasts that we hypothesize
      may be associated with differences in the potential resorptive activity of these
      cells.

PMID- 10942727
TI  - Modification of biophysical properties of lung epithelial Na(+) channels by
      dexamethasone.
AB  - There is considerable interest in identifying the basic mechanisms by which
      dexamethasone alters ion transport across the adult alveolar epithelium. Herein,
      we incubated synchronized A549 cells, a human alveolar epithelial cell line, with
      dexamethasone (1 microM) for 24-48 h. When normalized to HPRT (a housekeeping
      gene), A549 beta- and gamma-subunit mRNA levels for the human amiloride-sensitive
      epithelial sodium channel (hENaC), assessed by RT-PCR, increased by 1.6- and 17
      fold respectively, compared with control values (P < 0.05). These changes were
      abolished by actinomycin D, indicating transcriptional regulation. Western
      blotting studies revealed that dexamethasone also increased expression of beta-
      and gamma-hENaC protein levels. In contrast, alpha-hENaC mRNA increased by
      onefold (P > 0.05) and alpha-hENaC protein level was unchanged. Incubation of
      A549 cells with dexamethasone increased their whole cell amiloride-sensitive
      sodium currents twofold and decreased the K(0.5) for amiloride from 833 +/- 69 to
      22 +/- 5.4 nM (mean +/- SE; P < 0.01). Single channel recordings in the cell
      attached mode showed that dexamethasone treatment increased single channel open
      time and open probability threefold and decreased channel conductance from 8.63
      +/- 0.036 to 4. 4 +/- 0.027 pS (mean +/- SE; P < 0.01). We concluded that
      dexamethasone modulates the amiloride-sensitive Na(+) channels by differentially
      regulating the expression of beta- and gamma-subunits at the mRNA and protein
      levels in the human A549 cell line, with little effect on alpha-hENaC subunit.

PMID- 10942728
TI  - Cloning and functional expression of human retinal kir2.4, a pH-sensitive
      inwardly rectifying K(+) channel.
AB  - To identify novel potassium channel genes expressed in the retina, we screened a
      human retina cDNA library with an EST sequence showing partial homology to
      inwardly rectifying potassium (Kir) channel genes. The isolated cDNA yielded a
      2,961-base pair sequence with the predicted open reading frame showing strong
      homology to the rat Kir2. 4 (rKir2.4). Northern analysis of mRNA from human and
      bovine tissues showed preferential expression of Kir2.4 in the neural retina. In
      situ hybridization to sections of monkey retina detected Kir2.4 transcript in
      most retinal neurons. Somatic hybridization analysis and dual-color in situ
      hybridization to metaphase chromosomes mapped Kir2.4 to human chromosome 19 q13.1
      q13.3. Expression of human Kir2. 4 cRNA in Xenopus oocytes generated strong,
      inwardly rectifying K(+) currents that were enhanced by extracellular
      alkalinization. We conclude that human Kir2.4 encodes an inwardly rectifying K(+)
      channel that is preferentially expressed in the neural retina and that is
      sensitive to physiological changes in extracellular pH.

PMID- 10942729
TI  - Effects of microtubules and microfilaments on [Ca(2+)](i) and contractility in a
      reconstituted fibroblast fiber.
AB  - We used a reconstituted fiber formed when 3T3 fibroblasts are grown in collagen
      to characterize nonmuscle contractility and Ca(2+) signaling. Calf serum (CS) and
      thrombin elicited reversible contractures repeatable for >8 h. CS elicited dose
      dependent increases in isometric force; 30% produced the largest forces of 106 +/
      12 microN (n = 30), which is estimated to be 0.5 mN/mm(2) cell cross-sectional
      area. Half times for contraction and relaxation were 4.7 +/- 0.3 and 3.1 +/- 0.3
      min at 37 degrees C. With imposition of constant shortening velocities, force
      declined with time, yielding time-dependent force-velocity relations. Forces at 5
      s fit the hyperbolic Hill equation; maximum velocity (V(max)) was 0.035 +/- 0.
      002 L(o)/s. Compliance averaged 0.0076 +/- 0.0006 L(o)/F(o). Disruption of
      microtubules with nocodazole in a CS-contracted fiber had no net effects on
      force, V(max), or stiffness; force increased in 8, but decreased in 13, fibers.
      Nocodazole did not affect baseline intracellular Ca(2+) concentration
      ([Ca(2+)](i)) but reduced ( approximately 30%) the [Ca(2+)](i) response to CS.
      The force after nocodazole treatment was the primary determinant of stiffness and
      V(max), suggesting that microtubules were not a major component of fiber internal
      mechanical resistance. Cytochalasin D had major inhibitory effects on all
      contractile parameters measured but little effect on [Ca(2+)](i).

PMID- 10942730
TI  - In vitro system to study realistic pulsatile flow and stretch signaling in
      cultured vascular cells.
AB  - We developed a novel real-time servo-controlled perfusion system that exposes
      endothelial cells grown in nondistensible or distensible tubes to realistic pulse
      pressures and phasic shears at physiological mean pressures. A rate-controlled
      flow pump and linear servo-motor are controlled by digital proportional-integral
      derivative feedback that employs previously digitized aortic pressure waves as a
      command signal. The resulting pressure mirrors the recorded waveform and can be
      digitally modified to yield any desired mean and pulse pressure amplitude,
      typically 0-150 mmHg at shears of 0.5-15 dyn/cm(2). The system accurately
      reproduces the desired arterial pressure waveform and cogenerates physiological
      flow and shears by the interaction of pressure with the tubing impedance.
      Rectangular glass capillary tubes [1-mm inside diameter (ID)] are used for real
      time fluorescent imaging studies (i. e., pH(i), NO, Ca(2+)), whereas silicon
      distensible tubes (4-mm ID) are used for more chronic (i.e., 2-24 h) studies
      regarding signal transduction and gene expression. The latter have an elastic
      modulus of 12.4. 10(6) dyn/cm(2) similar to in vivo vessels of this size and are
      studied with the use of a benchtop system. The new approach provides the first in
      vitro application of realistic mechanical pulsatile forces on vascular cells and
      should facilitate studies of phasic shear and distension interaction and
      pulsatile signal transduction.

PMID- 10942731
TI  - Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle
      cells.
AB  - We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in
      skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide
      donor sodium nitroprusside prevented many of the effects of calcium ionophore on
      C(2)C(12) muscle cells, including preventing talin proteolysis and release into
      the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular
      protein. These results indicate that nitric oxide inhibition of calpain protected
      the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell
      permeable calpastatin peptide also protected the cells from proteolysis,
      confirming that ionophore-induced proteolysis was primarily calpain mediated. The
      activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside,
      and this inhibition was reversed by dithiothreitol. Previous incubation with the
      active site-targeted calpain inhibitor I prevented most of the sodium
      nitroprusside-induced inhibition of m-calpain activity. These data suggest that
      nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site
      cysteine. The results of this study indicate that nitric oxide produced
      endogenously by skeletal muscle and other cell types has the potential to inhibit
      m-calpain activity and cytoskeletal proteolysis.

PMID- 10942732
TI  - A metabolic control analysis of kinetic controls in ATP free energy metabolism in
      contracting skeletal muscle.
AB  - A system analysis of ATP free energy metabolism in skeletal muscle was made using
      the principles of metabolic control theory. We developed a network model of ATP
      free energy metabolism in muscle consisting of actomyosin ATPase, sarcoplasmic
      reticulum (SR) Ca(2+)-ATPase, and mitochondria. These components were sufficient
      to capture the major aspects of the regulation of the cytosolic ATP-to-ADP
      concentration ratio (ATP/ADP) in muscle contraction and had inherent homeostatic
      properties regulating this free energy potential. As input for the analysis, we
      used ATP metabolic flux and the cytosolic ATP/ADP at steady state at six
      contraction frequencies between 0 and 2 Hz measured in human forearm flexor
      muscle by (31)P-NMR spectroscopy. We used the mathematical formalism of metabolic
      control theory to analyze the distribution of fractional kinetic control of
      ATPase flux and the ATP/ADP in the network at steady state among the components
      over this experimental range and an extrapolated range of stimulation frequencies
      (up to 10 Hz). The control analysis showed that the contractile actomyosin ATPase
      has dominant kinetic control of ATP flux in forearm flexor muscle over the 0- to
      1.6-Hz range of contraction frequencies that resulted in steady states, as
      determined by (31)P-NMR. However, flux control begins to shift toward
      mitochondria at >1 Hz. This inversion of flux control from ATP demand to ATP
      supply control hierarchy progressed as the contraction frequency increased past 2
      Hz and was nearly complete at 10 Hz. The functional significance of this result
      is that, at steady state, ATP free energy consumption cannot outstrip the ATP
      free energy supply. Therefore, this reduced, three-component muscle ATPase system
      is inherently homeostatic.

PMID- 10942733
TI  - Clathrin in gastric acid secretory (parietal) cells: biochemical characterization
      and subcellular localization.
AB  - Clathrin from H-K-ATPase-rich membranes derived from the tubulovesicular
      compartment of rabbit and hog gastric acid secretory (parietal) cells was
      characterized biochemically, and the subcellular localization of membrane
      associated clathrin in parietal cells was characterized by immunofluorescence,
      electron microscopy, and immunoelectron microscopy. Clathrin from H-K- ATPase
      rich membranes was determined to be comprised of conventional clathrin heavy
      chain and a predominance of clathrin light chain A. Clathrin and adaptors could
      be induced to polymerize quantitatively in vitro, forming 120-nm-diameter
      basketlike structures. In digitonin-permeabilized resting parietal cells, the
      intracellular distribution of immunofluorescently labeled clathrin was suggestive
      of labeling of the tubulovesicular compartment. Clathrin was also unexpectedly
      localized to canalicular (apical) membranes, as were alpha-adaptin and dynamin,
      suggesting that this membrane domain of resting parietal cells is endocytotically
      active. At the ultrastructural level, clathrin was immunolocalized to canalicular
      and tubulovesicular membranes. H-K-ATPase was immunolocalized to the same
      membrane domains as clathrin but did not appear to be enriched at the specific
      subdomains that were enriched in clathrin. Finally, in immunofluorescently
      labeled primary cultures of parietal cells, in contrast to the H-K-ATPase,
      intracellular clathrin was found not to translocate to the apical membrane on
      secretagogue stimulation. Taken together, these biochemical and morphological
      data provide a framework for characterizing the role of clathrin in the
      regulation of membrane trafficking from tubulovesicles and at the canalicular
      membrane in parietal cells.

PMID- 10942734
TI  - Elevation of resting mitochondrial membrane potential of neural cells by
      cyclosporin A, BAPTA-AM, and bcl-2.
AB  - This study tested the hypothesis that the activity of the mitochondrial membrane
      permeability transition pore (PTP) affects the resting mitochondrial membrane
      potential (DeltaPsi) of normal, healthy cells and that the anti-apoptotic gene
      product Bcl-2 inhibits the basal activity of the PTP. DeltaPsi was measured by
      both fluorometric and nonfluorometric methods with SY5Y human neuroblastoma cells
      and with GT1-7 hypothalamic cells and PC12 pheochromocytoma cells in the absence
      and presence of Bcl-2 gene overexpression. The resting DeltaPsi of Bcl-2
      nonexpressing PC12 and wild-type SY5Y cells was increased significantly by the
      presence of the PTP inhibitor cyclosporin A (CsA) or by intracellular Ca(2+)
      chelation through exposure to the acetoxymethyl ester of 1, 2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). The DeltaPsi of Bcl-2
      overexpressing PC12 cells was larger than that of Bcl-2-negative cells and not
      significantly increased by CsA or by Ca(2+) chelation. CsA did not present a
      significant effect on the DeltaPsi monitored in unstressed GT1-7 cells but did
      inhibit the decrease in DeltaPsi elicited by the addition of t-butyl
      hydroperoxide, an oxidative inducer of the mitochondrial permeability transition.
      These results support the hypothesis that an endogenous PTP activity can
      contribute to lowering the basal DeltaPsi of some cells and that Bcl-2 can
      regulate the endogenous activity of the mitochondrial PTP.

PMID- 10942735
TI  - Dependence of KCC2 K-Cl cotransporter activity on a conserved carboxy terminus
      tyrosine residue.
AB  - K-Cl cotransporters (KCC) play fundamental roles in ionic and osmotic
      homeostasis. To date, four mammalian KCC genes have been identified. KCC2 is
      expressed exclusively in neurons. Injection of Xenopus oocytes with KCC2 cRNA
      induced a 20-fold increase in Cl(-)-dependent, furosemide-sensitive K(+) uptake.
      Oocyte swelling increased KCC2 activity 2-3 fold. A canonical tyrosine
      phosphorylation site is located in the carboxy termini of KCC2 (R1081-Y1087) and
      KCC4, but not in other KCC isoforms. Pharmacological studies, however, revealed
      no regulatory role for phosphorylation of KCC2 tyrosine residues. Replacement of
      Y1087 with aspartate or arginine dramatically reduced K(+) uptake under isotonic
      and hypotonic conditions. Normal or near-normal cotransporter activity was
      observed when Y1087 was mutated to phenylalanine, alanine, or isoleucine. A
      tyrosine residue equivalent to Y1087 is conserved in all identified KCCs from
      nematodes to humans. Mutation of the Y1087 congener in KCC1 to aspartate also
      dramatically inhibited cotransporter activity. Taken together, these results
      suggest that replacement of Y1087 and its congeners with charged residues
      disrupts the conformational state of the carboxy terminus. We postulate that the
      carboxy terminus plays an essential role in maintaining the functional
      conformation of KCC cotransporters and/or is involved in essential regulatory
      protein-protein interactions.

PMID- 10942736
TI  - The role of hydroxyl radical as a messenger in Cr(VI)-induced p53 activation.
AB  - The present study investigates whether reactive oxygen species (ROS) are involved
      in p53 activation, and if they are, which species is responsible for the
      activation. Our hypothesis is that hydroxyl radical (.OH) functions as a
      messenger for the activation of this tumor suppressor protein. Human lung
      epithelial cells (A549) were used to test this hypothesis. Cr(VI) was employed as
      the source of ROS due to its ability to generate a whole spectrum of ROS inside
      the cell. Cr(VI) is able to activate p53 by increasing the protein levels and
      enhancing both the DNA binding activity and transactivation ability of the
      protein. Increased cellular levels of superoxide radicals (O(2)(-).), hydrogen
      peroxide (H(2)O(2)), and.OH radicals were detected on the addition of Cr(VI) to
      the cells. Superoxide dismutase, by enhancing the production of H(2)O(2) from
      O(2)(-). radicals, increased p53 activity. Catalase, an H(2)O(2) scavenger,
      eliminated.OH radical generation and inhibited p53 activation. Sodium formate and
      aspirin,.OH radical scavengers, also suppressed p53 activation. Deferoxamine, a
      metal chelator, inhibited p53 activation by chelating Cr(V) to make it incapable
      of generating radicals from H(2)O(2). NADPH, which accelerated the one-electron
      reduction of Cr(VI) to Cr(V) and increased.OH radical generation, dramatically
      enhanced p53 activation. Thus.OH radical generated from Cr(VI) reduction in A549
      cells is responsible for Cr(VI)-induced p53 activation.

PMID- 10942737
TI  - Endothelial dysfunction in men with small LDL particles.
AB  - BACKGROUND: It is unknown whether LDL particle size is, independent of other
      lipids and lipoproteins, associated with endothelial dysfunction in vivo. METHODS
      AND RESULTS: We determined in vivo endothelial function in 34 healthy men by
      measuring forearm blood flow responses to intrabrachial artery infusions of
      acetylcholine (ACh, an endothelium-dependent vasodilator) and sodium
      nitroprusside (an endothelium-independent vasodilator). LDL peak particle size
      was measured with gradient gel electrophoresis. Men with small LDL particles (LDL
      diameter </=25.5 nm, n=10) had a 39% lower blood flow response to ACh than men
      with large LDL particles (LDL diameter >25. 5 nm, n=24, blood flow 6.9+/-3.6
      versus 11.4+/-5.1 mL/dL. min, P=0. 006). The groups had comparable LDL
      cholesterol concentrations (3. 9+/-0.6 versus 3.7+/-1.0 mmol/L, men with small
      versus large LDL particles), blood pressure, glucose concentrations, and body
      mass indexes. LDL size (r=0.45, P=0.01) but not HDL cholesterol (r=0.31, P=0.09)
      or triglycerides (r=-0.19, P=0.30) was significantly correlated with endothelium
      dependent vasodilation. Serum triglyceride concentrations and LDL size were
      inversely correlated (r=-0.44, P=0.01). In multivariate regression analysis, LDL
      size was the only significant determinant of the ACh-induced increase in blood
      flow. Sodium nitroprusside-stimulated endothelium-independent vasodilation was
      similar in both groups. CONCLUSIONS: Small LDL particles are associated with
      impaired in vivo endothelial function independent of HDL and LDL cholesterol and
      triglyceride concentrations. LDL size may therefore mediate adverse effects of
      hypertriglyceridemia on vascular function.

PMID- 10942738
TI  - Cost-effectiveness of treating hyperlipidemia in the presence of diabetes : who
      should be treated?
AB  - BACKGROUND: The objective of this study was to estimate the long-term costs and
      benefits of treating hyperlipidemia among diabetic patients with and without
      known cardiovascular disease after validating the Cardiovascular Life Expectancy
      Model. METHODS AND RESULTS: The model estimates were compared with the
      Scandinavian Simvastatin Survival Study (4S) and used to estimate the long-term
      costs and benefits of treatment with simvastatin. Simulations were performed for
      men and women, 40 to 70 years of age, having pretreatment LDL cholesterol values
      of 5.46, 4.34, and 3.85 mmol/L (211, 168, and 149 mg/dL). We forecasted the long
      term risk of cardiovascular events, the need for medical and surgical
      interventions, and the associated costs in 1996 US dollars. The model validated
      well against the observed results of the of the 4S diabetic patients. In this
      validation, the model estimates fell within the 95% confidence interval of the
      observed results for 7 of the 8 available end points (coronary deaths, total
      deaths, and so forth). Treatment with simvastatin for patients with
      cardiovascular disease is cost-effective for men and women, with or without
      diabetes. Among diabetic individuals without cardiovascular disease, the benefits
      of primary prevention were also substantial and the cost-effectiveness ratios
      attractive across a wide range of assumptions ( approximately $4000 to $40 000
      per year of life saved). These conclusions were robust even among diabetics with
      lower baseline LDL values and smaller LDL reductions as observed in the
      Cholesterol and Recruitment Events (CARE) trial. CONCLUSIONS: Among adults with
      hyperlipidemia, the presence of diabetes identifies men and women among whom
      lipid therapy is likely to be effective and cost-effective even in the absence of
      other risk factors or known cardiovascular disease.

PMID- 10942739
TI  - Dose-finding, safety, and tolerability study of an oral platelet glycoprotein
      IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral
      atherosclerotic disease.
AB  - BACKGROUND: Antiplatelet therapy is the mainstay of the treatment and secondary
      prevention of cardiovascular and cerebrovascular ischemic events. We assessed the
      safety, tolerability, and pharmacodynamics of lotrafiban, an oral platelet
      glycoprotein IIb/IIIa inhibitor, as a secondary prevention strategy in patients
      with cerebrovascular or cardiovascular disease. METHODS AND RESULTS: Overall, 451
      patients with a recent cardiovascular or cerebrovascular acute ischemic event
      were randomized in a double-blind fashion to 1 of 5 dosing regimens for 12 weeks:
      placebo or 5, 20, 50, or 100 mg lotrafiban, both twice daily with 300 to 325 mg/d
      aspirin. The primary end point was the incidence and tolerability of major and
      minor bleeding during treatment. Secondary end points included inhibition of
      platelet aggregation and clinical events. The placebo and lotrafiban 5-mg groups
      had similarly low rates of minor and major bleeding, but the 100-mg arm was
      terminated early because of excess major bleeding. Protocol-defined
      thrombocytopenia (<100 000 platelets/microL) occurred in 5 lotrafiban-treated
      patients (1.4%, 95% CI 0.2% to 2.7%) and 1 placebo patient (1.1%, 95% CI 0% to
      3.1%). Three lotrafiban-treated patients had a nadir platelet count <20
      000/microL (0.9%, 95% CI 0% to 1.8%). Lotrafiban produced dose-dependent
      inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly
      from placebo, whereas 100 mg inhibited aggregation by nearly 100%. CONCLUSIONS: 
      Lotrafiban provides dose-dependent platelet inhibition when administered to a
      range of patients with atherosclerosis. The level of platelet inhibition appears
      to correlate with bleeding risk and drug tolerability.

PMID- 10942740
TI  - Randomized crossover comparison of DDDR versus VDD pacing after atrioventricular
      junction ablation for prevention of atrial fibrillation. The atrial pacing peri
      ablation for paroxysmal atrial fibrillation (PA (3)) study investigators.
AB  - BACKGROUND: Some clinical data suggest that atrial-based pacing prevents
      paroxysmal atrial fibrillation (AF). This study tested the hypothesis that DDDR
      pacing compared with VDD pacing prevents AF after atrioventricular (AV) junction
      ablation. METHODS AND RESULTS: Patients were randomized to DDDR pacing (n=33) or
      to VDD pacing (n=34) after AV junction ablation and followed every 2 months for 6
      months. Patients then crossed over to the alternate pacing mode and were followed
      for an additional 6 months. Primary analysis included the time to first
      recurrence of sustained AF (duration >5 minutes), total AF burden, and the
      development of permanent AF. The time to first episode of AF was similar in the
      DDDR group (0.37 days, 95% CI 0.1 to 1.3 days) and the VDD pacing group (0.5
      days, 95% CI 0.2 to 1.7 days, P=NS). AF burden increased over time in both groups
      (P<0.01). At the 6-month follow-up, AF burden was 6.93 h/d (95% CI 4. 37 to 10.96
      h/d) in the DDDR group and 6.30 h/d (95% CI 3.99 to 9.94 h/d) in the VDD group
      (P=NS). Twelve (35%) patients in the DDDR group and 11 (32%) patients in the VDD
      group had permanent AF within 6 months of ablation. Within 1 year of follow-up,
      43% of patients had permanent AF. CONCLUSIONS: DDDR pacing compared with VDD
      pacing does not prevent paroxysmal AF over the long term in patients in the
      absence of antiarrhythmic drug therapy after total AV junction ablation. Many
      patients have permanent AF within the first year after ablation.

PMID- 10942741
TI  - Treating electrical storm : sympathetic blockade versus advanced cardiac life
      support-guided therapy.
AB  - BACKGROUND: Electrical storm (ES), defined as recurrent multiple ventricular
      fibrillation (VF) episodes, often occurs in patients with recent myocardial
      infarction. Because treating ES according to the Advanced Cardiac Life Support
      (ACLS) guidelines yields a poor outcome, we evaluated the efficacy of sympathetic
      blockade in treating ES patients and compared their outcome with that of patients
      treated according to the ACLS guidelines. METHODS AND RESULTS: Forty-nine
      patients (36 men, 13 women, mean age 57+/-10 years) who had ES associated with a
      recent myocardial infarction were separated into 2 groups. Patients in group 1
      (n=27) received sympathetic blockade treatment: 6 left stellate ganglionic
      blockade, 7 esmolol, and 14 propranolol. Patients in group 2 (n=22) received
      antiarrhythmic medication as recommended by the ACLS guidelines. Patient
      characteristics were similar in the 2 groups. The 1-week mortality rate was
      higher in group 2: 18 (82%) of the 22 patients died, all of refractory VF; 6
      (22%) of the 27 group 1 patients died, 3 of refractory VF (P<0.0001). Patients
      who survived the initial ES event did well over the 1-year follow-up period:
      Overall survival in group 1 was 67%, compared with 5% in group 2 (P<0.0001).
      CONCLUSIONS: Sympathetic blockade is superior to the antiarrhythmic therapy
      recommended by the ACLS guidelines in treating ES patients. Our study emphasizes
      the role of increased sympathetic activity in the genesis of ES. Sympathetic
      blockade-not class 1 antiarrhythmic drugs-should be the treatment of choice for
      ES.

PMID- 10942743
TI  - Effects of biatrial pacing in prevention of postoperative atrial fibrillation
      after coronary artery bypass surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) is common after coronary artery bypass
      surgery (CABG) and results in prolonged hospitalization. The purpose of this
      study was to evaluate the efficacy of biatrial pacing in preventing post-CABG AF
      compared with single-site atrial pacing. METHODS AND RESULTS: A total of 132
      patients who had no history of AF and who underwent CABG were randomized to 1 of
      the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right
      atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive
      atrial pacing was performed for 5 days. The incidence of AF was significantly
      reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%; RA,
      33.3%; control, 41. 9%; P<0.05). The mean length of hospital stay was
      significantly reduced in the BiA group. At baseline, the mean P-wave duration
      (P(dur)) and dispersion (P(dis)) were not prolonged. BiA pacing resulted in the
      most significant percentage of reduction in P(dis) when compared with the LA or
      RA groups (BiA, 42+/-8%; LA, 13+/-6%; RA, 10+/-9%; P<0.05 for BiA versus LA or
      RA). No significant differences existed in mean P(dur) and P(dis) between
      patients who developed AF and those who remained in sinus rhythm at baseline.
      However, only those patients who remained in sinus rhythm had a significant
      reduction in mean P(dur) and P(dis) after pacing therapy. CONCLUSIONS: Biatrial
      overdrive pacing is more effective in preventing post-CABG AF than single-site
      atrial pacing; this therapy also results in a shortened hospital stay. The
      overall reduction in atrial activation time with BiA pacing was reflected in the
      reduction in P(dis).

PMID- 10942742
TI  - Randomized comparison of antiarrhythmic drug therapy with implantable
      defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest
      Study Hamburg (CASH).
AB  - BACKGROUND: We conducted a prospective, multicenter, randomized comparison of
      implantable cardioverter-defibrillator (ICD) versus antiarrhythmic drug therapy
      in survivors of cardiac arrest secondary to documented ventricular arrhythmias.
      METHODS AND RESULTS: From 1987, eligible patients were randomized to an ICD,
      amiodarone, propafenone, or metoprolol (ICD versus antiarrhythmic agents
      randomization ratio 1:3). Assignment to propafenone was discontinued in March
      1992, after an interim analysis conducted in 58 patients showed a 61% higher all
      cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months.
      The study continued to recruit 288 patients in the remaining 3 study groups; of
      these, 99 were assigned to ICDs, 92 to amiodarone, and 97 to metoprolol. The
      primary end point was all-cause mortality. The study was terminated in March
      1998, when all patients had concluded a minimum 2-year follow-up. Over a mean
      follow-up of 57+/-34 months, the crude death rates were 36.4% (95% CI 26.9% to
      46.6%) in the ICD and 44.4% (95% CI 37.2% to 51.8%) in the amiodarone/metoprolol
      arm. Overall survival was higher, though not significantly, in patients assigned
      to ICD than in those assigned to drug therapy (1-sided P=0.081, hazard ratio
      0.766, [97.5% CI upper bound 1.112]). In ICD patients, the percent reductions in
      all-cause mortality were 41.9%, 39.3%, 28. 4%, 27.7%, 22.8%, 11.4%, 9.1%, 10.6%,
      and 24.7% at years 1 to 9 of follow-up. CONCLUSIONS: During long-term follow-up
      of cardiac arrest survivors, therapy with an ICD is associated with a 23%
      (nonsignificant) reduction of all-cause mortality rates when compared with
      treatment with amiodarone/metoprolol. The benefit of ICD therapy is more evident
      during the first 5 years after the index event.

PMID- 10942744
TI  - Randomized, double-blind trial of simultaneous right and left atrial epicardial
      pacing for prevention of post-open heart surgery atrial fibrillation.
AB  - BACKGROUND: The purpose of this study was to assess simultaneous right and left
      atrial pacing as prophylaxis for postoperative atrial fibrillation. METHODS AND
      RESULTS: In a double-blind, randomized fashion, 118 patients who underwent open
      heart surgery were assigned to right atrial pacing at 45 bpm (RA-AAI; n=39),
      right atrial triggered pacing at a rate of >/=85 bpm (RA-AAT; n=38), or
      simultaneous right and left atrial triggered pacing at a rate of >/=85 bpm (Bi
      AAT; n=41). Holter monitoring was performed for 4. 8+/-1.4 days after surgery to
      assess for episodes of atrial fibrillation lasting >5 minutes. The prevalence of
      postoperative atrial fibrillation was significantly less in the patients
      randomized to biatrial AAT pacing when compared with the other 2 pacing regimens
      (P=0.02). An episode of atrial fibrillation occurred in 4 (10%) of 41 patients in
      the Bi-AAT group compared with 11 (28%) of 39 patients in the RA-AAI group
      (P=0.03 versus Bi-AAT) and 12 (32%) of 38 patients in the RA-AAT group (P=0.01
      versus Bi-AAT). There was no difference in the occurrence of atrial fibrillation
      between the right atrial AAI and AAT groups (P=0.8). There was no significant
      difference among the 3 groups with regard to the number of postoperative hospital
      days (7.3+/-4.2 days), morbidity (5.1%), or mortality rate (2.5%). CONCLUSIONS:
      Simultaneous right and left atrial triggered pacing is well tolerated and
      significantly reduces the prevalence of post-open heart surgery atrial
      fibrillation.

PMID- 10942745
TI  - Quantitative ultrasonic tissue characterization can identify high-risk
      atherosclerotic alteration in human carotid arteries.
AB  - BACKGROUND: Recently, ultrasonic tissue characterization of the composition of
      plaques has been performed in a quantitative fashion on the basis of integrated
      backscatter (IBS) analysis, but most of those studies have used high-frequency
      ultrasound to obtain microscopic images. METHODS AND RESULTS: We performed B-mode
      measurement and IBS signal analysis with acoustic densitometry with a 7.5-MHz
      linear-array transducer in freshly excised human aortas (n=58) (normal,
      atheromatous, and fibrous tissue) obtained at autopsy. Atheromatous and fibrous
      tissue had a similar intima-media thickness (IMT), but the IBS value in
      atheromatous specimens was lower than that in fibrous specimens. We further
      applied this method to human carotid ultrasonography. The subjects were young (80
      regions), middle aged with 1 or no coronary risk factors (low risk) (120
      regions), middle aged with >/=2 coronary risk factors (high risk) (240 regions),
      or elderly (80 regions) or were patients with myocardial infarction (MI) with
      multivessel disease (90 regions). The IMT was similar in middle-aged, elderly,
      and MI subjects. In contrast, the IBS value was significantly higher in elderly
      subjects and lower in high-risk middle-aged and MI subjects compared with that in
      low-risk middle-aged subjects. The percent of regions diagnosed as atheromatous
      (IBS less than mean minus 2-SD value of IBS in young subjects) was 11% in low
      risk middle-aged subjects, 29% in high-risk middle-aged subjects, and 63% in the
      MI group. CONCLUSIONS: In conjunction with conventional B-mode imaging, IBS
      analysis with carotid ultrasonography appeared to provide prognostic information
      to identify a high-risk group with systemic atherosclerosis, which could lead to
      coronary heart disease in individuals with early-stage disease.

PMID- 10942746
TI  - Specific cellular features of atheroma associated with development of neointima
      after carotid endarterectomy: the carotid atherosclerosis and restenosis study.
AB  - BACKGROUND: The purpose of this study was to investigate whether some cellular
      and molecular features of tissue retrieved at carotid endarterectomy are
      associated with the extent of neointima formation at ultrasound follow-up.
      METHODS AND RESULTS: One hundred fifty patients were studied. Endarterectomy
      specimens were tested by immunocytochemistry with the use of (1) monoclonal
      antibodies that identify smooth muscle cells (SMCs) and fetal-type SMCs on the
      basis of smooth muscle and nonmuscle myosin content, (2) the anti-macrophage HAM
      56, and (3) the anti-lymphocyte CD45RO. The maximum intima-media thickness (M
      IMT) of the revascularized vessel was assessed by the use of B-mode
      ultrasonography 6 months after surgery. The M-IMT values were related positively
      to the number of SMCs (r=0.534, P<0.0005) and negatively to that of macrophages
      and lymphocytes (r=-0.428, P<0.0005, and -0.538, P=0.001, respectively). Patients
      were classified as class 1 (M-IMT </=1.0 mm), class 2 (1. 0<M-IMT</=1.3 mm), and
      class 3 (M-IMT >1.3 mm). An abundance of SMCs, mostly of fetal type, was found in
      the plaque of class 3 patients, whereas lesions from class 1 patients were rich
      in macrophages and lymphocytes. In the multivariate analysis, factors related to
      M-IMT were the number of SMCs and the percentage of fetal-type SMCs present in
      the plaque. CONCLUSIONS: Although the classic risk factors did not play a role,
      an abundance of SMCs and a scarcity of macrophages characterized the primary
      lesion of patients in whom neointima developed after surgery. In patients in whom
      neointima did not develop, lesions were rich in macrophages and lymphocytes. This
      approach can be useful in defining patients at risk of restenosis.

PMID- 10942747
TI  - Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E
      deficient mouse.
AB  - BACKGROUND: Human herpesviruses have been implicated but not proven to be
      involved in the etiology of atherosclerosis. To determine whether there is a
      causal relationship, the effect of herpesvirus infection on the development of
      atherosclerosis was assessed in the apolipoprotein E-deficient (apoE-/-) mouse.
      METHODS AND RESULTS: In the present study, 3- to 4-week-old apoE-/- mice were
      infected with murine gamma-herpesvirus-68 (MHV-68). Atheroma formation was
      accelerated over a 24-week period in infected apoE-/- mice compared with control
      uninfected apoE-/- mice. Acceleration of atherosclerosis was reduced by antiviral
      drug administration. Histological analysis of the atheromatous plaques showed no
      difference between lesions of infected and control mice. Viral mRNA was present
      in the aortas of infected mice before lesion development on day 5 after
      infection. This suggests that the virus may initiate endothelial injury, which is
      believed to be an early event in the development of atherosclerosis. Therefore,
      the virus may play a direct role in atherosclerosis rather than be an "innocent
      bystander." CONCLUSIONS: These data demonstrate that a gamma-herpesvirus can
      accelerate atherosclerosis in the apoE-/- mouse. This study provides the first
      report of a murine model in which to study the causative role of herpesvirus
      infection in the development of atherosclerosis.

PMID- 10942748
TI  - CC chemokine I-309 is the principal monocyte chemoattractant induced by
      apolipoprotein(a) in human vascular endothelial cells.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerosis; however,
      the mechanisms are unclear. We previously reported that Lp(a) stimulated human
      vascular endothelial cells to produce monocyte chemotactic activity. The
      apolipoprotein(a) [apo(a)] portion of Lp(a) was the active moiety. METHODS AND
      RESULTS: We now describe the identification of the chemotactic activity as being
      due to the CC chemokine I-309. The carboxy-terminal domain of apo(a) containing 6
      type-4 kringles (types 5 to 10), kringle V, and the protease domain was
      demonstrated to contain the I-309-inducing portion. Polyclonal and monoclonal
      anti-I-309 antibodies as well as an antibody against a portion of the
      extracellular domain of CCR8, the I-309 receptor, inhibited the increase in
      monocyte chemotactic activity induced by apo(a). I-309 antisense oligonucleotides
      also inhibited the induction of endothelial monocyte chemotactic activity by
      apo(a). I-309 mRNA was identified in human umbilical vein endothelial cells.
      Apo(a) induced an increase in I-309 protein in the endothelial cytoplasm and in
      the conditioned medium. Immunohistochemical studies have identified I-309 in
      endothelium, macrophages, and extracellular areas of human atherosclerotic
      plaques and have found that I-309 colocalized with apo(a). CONCLUSIONS: These
      data establish that I-309 is responsible for the monocyte chemotactic activity
      induced in human umbilical vein endothelial cells by Lp(a). The identification of
      the endothelial cell as a source for I-309 suggests that this chemokine may
      participate in vessel wall biology. Our data also suggest that I-309 may play a
      role in mediating the effects of Lp(a) in atherosclerosis.

PMID- 10942749
TI  - Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells
      attenuates mitogenic signaling via G protein-coupled and platelet-derived growth
      factor receptors.
AB  - BACKGROUND: Neointimal hyperplasia involves activation of smooth muscle cells
      (SMCs) by several G protein-coupled receptor (GPCR) agonists, including
      endothelin-1, angiotensin II, thrombin, and thromboxane A(2). Signaling of many
      GPCRs is diminished by GPCR kinase-2 (GRK2). We therefore tested whether
      overexpression of GRK2 in SMCs could diminish mitogenic signaling elicited by
      agonists implicated in the pathogenesis of neointimal hyperplasia. METHODS AND
      RESULTS: Overexpression of GRK2 was achieved in primary rabbit aortic SMCs with a
      recombinant adenovirus. Control SMCs were infected with an empty vector
      adenovirus. Inositol phosphate responses to endothelin-1, angiotensin II,
      thrombin agonist peptide, and platelet-derived growth factor (PDGF) were
      attenuated by 37% to 72% in GRK2-overexpressing cells (P<0.01), but the response
      to the thromboxane A(2) analogue U46619 was unaffected. GRK2 also inhibited SMC
      [(3)H]thymidine incorporation stimulated not only by these agonists (by 30% to
      60%, P<0.01) but also by 10% FBS (by 35%, P<0. 05). However, GRK2 overexpression
      had no effect on epidermal growth factor-induced [(3)H]thymidine incorporation.
      Agonist-induced tyrosine phosphorylation of the PDGF-beta receptor, but not the
      epidermal growth factor receptor, was reduced in GRK2-overexpressing SMCs. GRK2
      overexpression also reduced SMC proliferation in response to endothelin-1, PDGF,
      and 10% FBS by 62%, 51%, and 29%, respectively (P<0.01), without any effect on
      SMC apoptosis. CONCLUSIONS: GRK2 overexpression diminishes SMC mitogenic
      signaling and proliferation stimulated by PDGF or agonists for several GPCRs.
      Gene transfer of GRK2 may therefore be therapeutically useful for neointimal
      hyperplasia.

PMID- 10942750
TI  - Adenosine primes the opening of mitochondrial ATP-sensitive potassium channels: a
      key step in ischemic preconditioning?
AB  - BACKGROUND: Adenosine can initiate ischemic preconditioning, and mitochondrial
      ATP-sensitive potassium (K(ATP)) channels have emerged as the likely effectors.
      We sought to determine the mechanistic interactions between these 2 observations.
      METHODS AND RESULTS: The mitochondrial flavoprotein oxidation induced by
      diazoxide (100 micromol/L) was used to quantify mitochondrial K(ATP) channel
      activity in intact rabbit ventricular myocytes. Adenosine (100 micromol/L)
      increased mitochondrial K(ATP) channel activity and abbreviated the latency to
      mitochondrial K(ATP) channel opening. These potentiating effects were entirely
      prevented by the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline
      (100 micromol/L) or by the protein kinase C inhibitor polymyxin B (50
      micromol/L). The effects of adenosine and diazoxide reflected mitochondrial
      K(ATP) channel activation, because they could be blocked by the mitochondrial
      K(ATP) channel blocker 5-hydroxydecanoate (500 micromol/L). In a cellular model
      of simulated ischemia, adenosine mitigated cell injury; this cardioprotective
      effect was blocked by 5-hydroxydecanoate but not by the surface-selective K(ATP)
      channel blocker HMR1098. Moreover, adenosine augmented the cardioprotective
      effect of diazoxide. A quantitative model of mitochondrial K(ATP) channel gating
      reproduced the major experimental findings. CONCLUSIONS: Our results support the
      hypothesis that adenosine receptor activation primes the opening of mitochondrial
      K(ATP) channels in a protein kinase C-dependent manner. The findings provide
      tangible links among various key elements in the preconditioning cascade.

PMID- 10942751
TI  - Increased activity of nuclear factor-kappaB participates in cardiovascular
      remodeling induced by chronic inhibition of nitric oxide synthesis in rats.
AB  - BACKGROUND: Chronic inhibition of endothelial nitric oxide (NO) synthesis by the
      administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces
      early vascular inflammatory changes [monocyte infiltration into coronary vessels,
      nuclear factor-kappaB (NF-kappaB) activation, and monocyte chemoattractant
      protein-1 expression] as well as subsequent arteriosclerosis (medial thickening
      and perivascular fibrosis) and cardiac fibrosis. However, no direct evidence for
      the importance of NF-kappaB in this process is known. METHODS AND RESULTS: We
      examined the effect of a cis element decoy strategy to address the functional
      importance of NF-kappaB in the pathogenesis of cardiovascular remodeling. We
      found here that in vivo transfection of cis element decoy oligodeoxynucleotides
      against NF-kappaB to hearts prevented the L-NAME-induced early inflammation and
      subsequent coronary vascular medial thickening. In contrast, NF-kappaB decoy
      oligodeoxynucleotide transfection did not decrease the development of fibrosis,
      the expression of transforming growth factor-beta(1) mRNA, or systolic pressure
      overload induced by L-NAME administration. CONCLUSIONS: The NF-kappaB system
      participates importantly in the development of early vascular inflammation and
      subsequent medial thickening but not in fibrogenesis in this model. The present
      study may provide a new aspect of how endothelium-derived NO contributes to anti
      inflammatory and/or antiarteriosclerotic properties of the vascular endothelium
      in vivo.

PMID- 10942752
TI  - Transcatheter implantation of a bovine valve in pulmonary position: a lamb study.
AB  - BACKGROUND: Pulmonary regurgitation can lead to severe right ventricular
      dysfunction, which is a delicate postoperative problem in the long-term follow-up
      of patients who had surgery for congenital heart diseases. Clinical conditions of
      patients suffering from pulmonary valve incompetence are improved by valve
      replacement with a prosthetic valve. To date, the surgical approach is the only
      option to replace a pulmonary valve. We report the first experience of
      percutaneous pulmonary valve implantation. METHODS AND RESULTS: A fresh bovine
      jugular vein containing a native valve was sutured into a vascular stent and then
      cross-linked with a 0.6% glutaraldehyde solution for 36 hours. After being hand
      crimped onto a balloon catheter, the device was inserted percutaneously according
      to standard stent-placing techniques. The valved stent was finally deployed in
      the position of the native pulmonary valve of the lamb. Hemodynamic evaluation
      was carried out before and 2 months after implantation. Anatomic evaluation was
      finally performed. Percutaneous pulmonary valve replacement was successful in 5
      lambs. No complications were noted. Early and late angiographic and hemodynamic
      studies confirmed a good position of the stents with a competent valve at the end
      of the protocol. One stent was slightly stenotic, with macroscopically visible
      calcifications. CONCLUSIONS: Nonsurgical implantation of pulmonary valves is
      possible in the lamb. This new technique is similar to standard stent
      implantation. Thus, it should be feasible in humans, in whom it will lead to a
      significant reduction of reoperations in patients in need of pulmonary valve
      replacement.

PMID- 10942753
TI  - Images in cardiovascular medicine. Labile repolarization from "cell to bedside".

PMID- 10942754
TI  - Improved regional wall motion 6 months after direct myocardial revascularization
      (DMR) with the NOGA DMR system.

PMID- 10942755
TI  - Sentinel emergency departments report safety net frayed by uninsured and managed
      care.

PMID- 10942756
TI  - Interaction of linker for activation of T cells with multiple adapter proteins in
      platelets activated by the glycoprotein VI-selective ligand, convulxin.
AB  - The snake venom toxin convulxin activates platelets through the collagen receptor
      glycoprotein VI (GPVI)/Fc receptor gamma-chain (FcR gamma-chain) complex leading
      to tyrosine phosphorylation and activation of the tyrosine Syk and phospholipase
      Cgamma2 (PLCgamma2). In the present study, we demonstrate that convulxin is a
      considerably more powerful agonist than collagen or the GPVI-selective collagen
      related peptide (CRP). Confirmation that the response to convulxin is mediated
      solely via Syk was provided by studies on Syk-deficient platelets. The increase
      in phosphorylation of the FcR gamma-chain is associated with marked increases in
      tyrosine phosphorylation of downstream proteins including Syk, linker for
      activation of T cells (LAT), SLP-76, and PLCgamma2. The transmembrane adapter LAT
      coprecipitates with SLP-76 and PLCgamma2, as well as with a number of other
      adapter proteins, some of which have not been previously described in platelets,
      including Cbl, Grb2, Gads, and SKAP-HOM. Gads is constitutively associated with
      SLP-76 and is probably the protein bridging its association with LAT. There was
      no detectable association between Grb2 and SLP-76 in control or stimulated cells,
      suggesting that the interaction of LAT with Grb2 is present in a separate complex
      to that of LAT-Gads-SLP-76. These results show that the trimeric convulxin
      stimulates a much greater phosphorylation of the FcR gamma-chain and subsequent
      downstream responses relative to CRP and collagen, presumably because of its
      ability to cause a greater degree of cross-linking of GPVI. The adapter LAT
      appears to play a critical role in recruiting a number of other adapter proteins
      to the surface membrane in response to activation of GPVI, presumably at sites of
      glycolipid-enriched microdomains, enabling an organized signaling cascade that
      leads to platelet activation.

PMID- 10942757
TI  - Isolation and characterization of gomesin, an 18-residue cysteine-rich defense
      peptide from the spider Acanthoscurria gomesiana hemocytes with sequence
      similarities to horseshoe crab antimicrobial peptides of the tachyplesin family.
AB  - We have purified a small size antimicrobial peptide, named gomesin, from the
      hemocytes of the unchallenged tarantula spider Acanthoscurria gomesiana. Gomesin
      has a molecular mass of 2270.4 Da, with 18 amino acids, including a pyroglutamic
      acid as the N terminus, a C-terminal arginine alpha-amide, and four cysteine
      residues forming two disulfide bridges. This peptide shows marked sequence
      similarities to antimicrobial peptides from other arthropods such as tachyplesin
      and polyphemusin from horseshoe crabs and androctonin from scorpions.
      Interestingly, it also shows sequence similarities to protegrins, antimicrobial
      peptides from porcine leukocytes. Gomesin strongly affects bacterial growth, as
      well as the development of filamentous fungi and yeast. In addition, we showed
      that gomesin affects the viability of the parasite Leishmania amazonensis.

PMID- 10942758
TI  - Roles of individual N-glycans for ATP potency and expression of the rat P2X1
      receptor.
AB  - P2X(1) receptor subunits assemble in the ER of Xenopus oocytes to homotrimers
      that appear as ATP-gated cation channels at the cell surface. Here we address the
      extent to which N-glycosylation contributes to assembly, surface appearance, and
      ligand recognition of P2X(1) receptors. SDS-polyacrylamide gel electrophoresis
      (PAGE) analysis of glycan minus mutants carrying Gln instead of Asn at five
      individual NXT/S sequons reveals that Asn(284) remains unused because of a
      proline in the +4 position. The four other sites (Asn(153), Asn(184), Asn(210),
      and Asn(300)) carry N-glycans, but solely Asn(300) located only eight residues
      upstream of the predicted reentry loop of P2X(1) acquires complex-type
      carbohydrates. Like parent P2X(1), glycan minus mutants migrate as homotrimers
      when resolved by blue native PAGE. Recording of ATP-gated currents reveals that
      elimination of Asn(153) or Asn(210) diminishes or increases functional expression
      levels, respectively. In addition, elimination of Asn(210) causes a 3-fold
      reduction of the potency for ATP. If three or all four N-glycosylation sites are
      simultaneously eliminated, formation of P2X(1) receptors is severely impaired or
      abolished, respectively. We conclude that at least one N-glycan per subunit of
      either position is absolutely required for the formation of P2X(1) receptors and
      that individual N-glycans possess marked positional effects on expression levels
      (Asn(154), Asn(210)) and ATP potency (Asn(210)).

PMID- 10942759
TI  - Glycine-rich region of mitochondrial processing peptidase alpha-subunit is
      essential for binding and cleavage of the precursor proteins.
AB  - Mitochondrial processing peptidase, a metalloendopeptidase consisting of alpha-
      and beta-subunits, specifically recognizes a large variety of mitochondrial
      precursor proteins and cleaves off amino-terminal extension peptides. The alpha
      subunit has a characteristic glycine-rich segment in the middle portion. To
      elucidate the role of the region in processing functions of the enzyme, deletion
      or site-directed mutations were introduced, and effects on kinetic parameters and
      substrate binding of the enzyme were analyzed. Deletion of three residues of the
      region, Phe(289) to Ala(291), led to a dramatic reduction in processing activity
      to practically zero. Mutation of Phe(289), Lys(296), and Met(298) to alanine
      resulted in a decrease in the activity, but these mutations had no apparent
      effect on interactions between the two subunits, indicating that reduction in
      processing activity is not due to structural disruption at the interface
      interacting with the beta-subunit. Although the mutant enzymes, Phe289Ala,
      Lys296Ala, and Met298Ala, had an approximate 10-fold less affinity for substrate
      peptides than did that of the wild type, the deletion mutant, delta 289-291,
      showed an extremely low affinity. Thus, shortening of the glycine-rich stretch
      led to a dramatic reduction of interaction between the enzyme and substrate
      peptides and cleavage reaction, whereas mutation of each amino acid in this
      region seemed to affect primarily the cleavage reaction.

PMID- 10942760
TI  - The platelet integrin alpha IIbbeta 3 has an endogenous thiol isomerase activity.
AB  - Integrins are cysteine-rich heterodimeric cell-surface adhesion molecules that
      alter their affinity for ligands in response to cellular activation. The
      molecular mechanisms involved in this activation of integrins are not understood.
      Treatment with the thiol-reducing agent, dithiothreitol, can induce an activation
      like state in many integrins suggesting that cysteine-cysteine dithiol bonds are
      important for the receptor's tertiary structure and may be involved in activation
      induced conformational changes. Here we demonstrate that the platelet-specific
      integrin, alpha(IIb)beta(3), contains an endogenous thiol isomerase activity,
      predicted from the presence of the tetrapeptide motif, CXXC, in each of the
      cysteine-rich repeats of the beta(3) polypeptide. This motif comprises the active
      site in enzymes involved in disulfide exchange reactions, including protein
      disulfide isomerase (EC ) and thioredoxin. Intrinsic thiol isomerase activity is
      also observed in the related integrin, alpha(v)beta(3), which shares a common
      beta-subunit. Thiol isomerase activity within alpha(IIb)beta(3) is time-dependent
      and saturable, and is inhibited by the protein-disulfide isomerase inhibitor,
      bacitracin. Furthermore, this activity is calcium-sensitive and is regulated in
      the EDTA-stabilized conformation of the integrin. This novel demonstration of an
      enzymatic activity associated with an integrin subunit suggests that altered
      thiol bonding within the integrin or its substrates may be locally modified
      during alpha(IIb)beta(3) activation.

PMID- 10942761
TI  - Lysyl oxidase activates the transcription activity of human collagene III
      promoter. Possible involvement of Ku antigen.
AB  - Lysyl oxidase is an extracellular enzyme that controls the maturation of collagen
      and elastin. Lysyl oxidase and collagen III often show similar expression
      patterns in fibrotic tissues. Therefore, we investigated the influence of lysyl
      oxidase overexpression on the promoter activity of human COL3A1 gene. Our results
      showed that when COS-7 cells overexpressed the mature form of lysyl oxidase, the
      activity of the human COL3A1 promoter was increased up to an average of 12 times
      when tested by luciferase reporter assay. The effect was specific, because other
      promoters were not affected. Moreover, lysyl oxidase effect was abolished by beta
      aminopropionitrile, a specific inhibitor of its catalytic activity.
      Electrophoretic mobility shift assay showed a binding activity in the region from
      -101 to -77 that was significantly increased by lysyl oxidase overexpression. The
      binding was specifically competed by the cold probe, and the mutagenesis of this
      region abolished both the binding activity in gel retardation and lysyl oxidase
      stimulation of COL3A1 promoter in transfection experiments. We identified the
      binding activity as Ku antigen in its two components: Ku80 and Ku70. This study
      suggests a new coordinated mechanism by which lysyl oxidase might control the
      development of fibrosis.

PMID- 10942762
TI  - Characterization of luminal paneth cell alpha-defensins in mouse small intestine.
      Attenuated antimicrobial activities of peptides with truncated amino termini.
AB  - Paneth cells at the base of small intestinal crypts secrete apical granules that
      contain antimicrobial peptides including alpha-defensins, termed cryptdins. Using
      an antibody specific for mouse cryptdin-1, -2, -3, and -6, immunogold
      localization studies demonstrated that cryptdins are constituents of mouse Paneth
      cell secretory granules. Several cryptdin peptides have been purified from rinses
      of adult mouse small intestine by gel filtration and reverse-phase high
      performance liquid chromatography. Their primary structures were determined by
      peptide sequencing, and their antimicrobial activities were compared with those
      of the corresponding tissue forms. The isolated luminal cryptdins included
      peptides identical to the tissue forms of cryptdin-2, -4, and -6 as well as
      variants of cryptdin-1, -4, and -6 that have N termini truncated by one or two
      residues. In assays of antimicrobial activity against Staphylococcus aureus,
      Escherichia coli, and the defensin-sensitive Salmonella typhimurium phoP(-)
      mutant, full-length cryptdins had the same in vitro antibacterial activities
      whether isolated from tissue or from the lumen. In contrast, the N-terminal
      truncated (des-Leu), (des-Leu-Arg)-cryptdin-6, and (des-Gly)-cryptdin-4 peptides
      were markedly less active. The microbicidal activities of recombinant cryptdin-4
      and (des-Gly)-cryptdin-4 peptides against E. coli, and S. typhimurium showed that
      the N-terminal Gly residue or the length of the cryptdin-4 N terminus are
      determinants of microbicidal activity. Innate immunity in the crypt lumen may be
      modulated by aminopeptidase modification of alpha-defensins after peptide
      secretion.

PMID- 10942763
TI  - Replacement of the distal glycine 139 transforms human heme oxygenase-1 into a
      peroxidase.
AB  - The human heme oxygenase-1 crystal structure suggests that Gly-139 and Gly-143
      interact directly with iron-bound ligands. We have mutated Gly-139 to an alanine,
      leucine, phenylalanine, tryptophan, histidine, or aspartate, and Gly-143 to a
      leucine, lysine, histidine, or aspartate. All of these mutants bind heme, but
      absorption and resonance Raman spectroscopy indicate that the water coordinated
      to the iron atom is lost in several of the Gly-139 mutants, giving rise to
      mixtures of hexacoordinate and pentacoordinate ligation states. The active site
      perturbation is greatest when large amino acid side chains are introduced. Of the
      Gly-139 mutants investigated, only G139A catalyzes the NADPH-cytochrome P450
      reductase-dependent oxidation of heme to biliverdin, but most of them exhibit a
      new H(2)O(2)-dependent guaiacol peroxidation activity. The Gly-143 mutants, all
      of which have lost the water ligand, have no heme oxygenase or peroxidase
      activity. The results establish the importance of Gly-139 and Gly-143 in
      maintaining the appropriate environment for the heme oxygenase reaction and show
      that Gly-139 mutations disrupt this environment, probably by displacing the
      distal helix, converting heme oxygenase into a peroxidase. The principal role of
      the heme oxygenase active site may be to suppress the ferryl species formation
      responsible for peroxidase activity.

PMID- 10942764
TI  - Attractive interhelical electrostatic interactions in the proline- and acidic
      rich region (PAR) leucine zipper subfamily preclude heterodimerization with other
      basic leucine zipper subfamilies.
AB  - Basic region-leucine zipper (B-ZIP) proteins homo- or heterodimerize to bind
      sequence-specific double-stranded DNA. We present circular dichroism (CD) thermal
      denaturation data on vitellogenin promoter-binding protein (VBP), a member of the
      PAR subfamily of B-ZIP proteins that also includes thyroid embryonic factor,
      hepatocyte leukemia factor, and albumin site D-binding protein. VBP does not
      heterodimerize with B-ZIP domains from C/EBP alpha, JUND, or FOS. We describe a
      dominant negative protein, A-VBP, that contains the VBP leucine zipper and an
      acidic amphipathic protein sequence that replaces the basic region critical for
      DNA binding. The acidic extension forms a coiled coil structure with the VBP
      basic region in the VBP.A-VBP heterodimer. This new alpha-helical structure
      extends the leucine zipper N-terminally, stabilizing the complex by 2.0 kcal/mol.
      A-VBP abolishes DNA binding of VBP in an equimolar competition assay, but does
      not affect DNA binding even at 100-fold excess of CREB, C/EBP alpha, or FOS/JUND.
      Likewise, proteins containing the acidic extension appended to seven other
      leucine zippers do not inhibit VBP DNA binding. We show that conserved g <--> e'
      or i, i' +5 salt bridges are sufficient to confer specificity to VBP by mutating
      the C/EBPalpha leucine zipper to contain the g <--> e' salt bridges that
      characterize VBP. A-VBP heterodimerizes with this mutant C/EBP, preventing it
      from binding to DNA. These conserved g <--> e' electrostatic interactions define
      the specificity of the PAR subfamily of B-ZIP proteins and preclude interaction
      with other B-ZIP subfamilies.

PMID- 10942765
TI  - Functional reconstitution of substrate transport by purified multidrug resistance
      protein MRP1 (ABCC1) in phospholipid vesicles.
AB  - The 190-kDa multidrug resistance protein MRP1 (ABCC1) is a polytopic
      transmembrane protein belonging to the ATP-binding cassette transporter
      superfamily. In addition to conferring resistance to various antineoplastic
      agents, MRP1 is a transporter of conjugated organic anions, including the
      cysteinyl leukotriene C(4) (LTC(4)). We previously characterized the ATPase
      activity of reconstituted immunoaffinity-purified native MRP1 and showed it could
      be stimulated by its organic anion substrates (Mao, Q., Leslie, E. M., Deeley, R.
      G., and Cole, S. P. C. (1999) Biochim. Biophys. Acta 1461, 69-82). Here we show
      that purified reconstituted MRP1 is also capable of active transport of its
      substrates. Thus LTC(4) uptake by MRP1 proteoliposomes was osmotically sensitive
      and could be inhibited by two MRP1-specific monoclonal antibodies. LTC(4) uptake
      was also markedly reduced by the competitive inhibitor, S-decyl-glutathione, as
      well as by the MRP1 substrates 17 beta-estradiol 17-beta-(d-glucuronide),
      oxidized glutathione, and vincristine in the presence of reduced glutathione. The
      K(m) for ATP and LTC(4) were 357 +/- 184 microm and 366 +/- 38 nm, respectively,
      and 2.14 +/- 0.75 microm for 17 beta-estradiol 17-beta-(d-glucuronide). Transport
      of vincristine required the presence of both ATP and GSH. Conversely, GSH
      transport was stimulated by vincristine and verapamil. Our data represent the
      first reconstitution of transport competent purified native MRP1 and confirm that
      MRP1 is an efflux pump, which can transport conjugated organic anions and co
      transport vincristine together with GSH.

PMID- 10942766
TI  - Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2
      creates the MPM-2 phosphoepitope on Ser-1469.
AB  - DNA topoisomerase II alpha is required for chromatin condensation during
      prophase. This process is temporally linked with the appearance of mitosis
      specific phosphorylation sites on topoisomerase IIalpha including one recognized
      by the MPM-2 monoclonal antibody. We now report that the ability of mitotic
      extracts to create the MPM-2 epitope on human topoisomerase II alpha is abolished
      by immunodepletion of protein kinase CK2. Furthermore, the MPM-2 phosphoepitope
      on topoisomerase II alpha can be generated by purified CK2. Phosphorylation of C
      truncated topoisomerase II alpha mutant proteins conclusively shows, that the MPM
      2 epitope is present in the last 163 amino acids. Use of peptides containing all
      conserved CK2 consensus sites in this region indicates that only the peptide
      containing Arg-1466 to Ala-1485 is able to compete with topoisomerase II alpha
      for binding of the MPM-2 antibody. Replacement of Ser-1469 with Ala abolishes the
      ability of the phosphorylated peptide to bind to the MPM-2 antibody while a
      peptide containing phosphorylated Ser-1469 binds tightly. Surprisingly, the MPM-2
      phosphoepitope influences neither the catalytic activity of topoisomerase II
      alpha nor its ability to form molecular complexes with CK2 in vitro. In
      conclusion, we have identified protein kinase CK2 as a new MPM-2 kinase able to
      phosphorylate an important mitotic protein, topoisomerase II alpha, on Ser-1469.

PMID- 10942767
TI  - Cpr6 and Cpr7, two closely related Hsp90-associated immunophilins from
      Saccharomyces cerevisiae, differ in their functional properties.
AB  - Hsp90 is an abundant cytosolic molecular chaperone. It controls the folding of
      target proteins including steroid hormone receptors and kinases in complex with
      several partner proteins. Prominent members of this protein family are large
      peptidyl prolyl cis/trans isomerases (PPIases), which catalyze the cis/trans
      isomerization of prolyl peptide bonds in proteins and possess chaperone activity.
      In Saccharomyces cerevisiae, two closely related large Hsp90-associated PPIases,
      Cpr6 and Cpr7, exist. We show here that these homologous proteins bind with
      comparable affinity to Hsp90 but exhibit significant structural and functional
      differences. Cpr6 is more stable than Cpr7 against thermal denaturation and
      displays an up to 100-fold higher PPIase activity. In contrast, the chaperone
      activity of Cpr6 is much lower than that of Cpr7. Based on these results we
      suggest that the two immunophilins perform overlapping but not identical tasks in
      the Hsp90 chaperone cycle.

PMID- 10942768
TI  - A nuclear localization signal is essential for stress-induced dimer-to-trimer
      transition of heat shock transcription factor 3.
AB  - Expression of heat shock genes is regulated mainly at the level of transcription
      by heat shock transcription factors (HSFs). In avian, HSF1 and HSF3 are
      maintained in a cryptic monomer and dimer form, respectively, in the cytoplasm in
      the absence of stress. Upon heat stress, they undergo conformational change
      associated with the formation of a trimer and nuclear translocation. In this
      study, we identified regions that are necessary for the dimer-to-trimer
      transition of chicken HSF3 (cHSF3) upon stress conditions. One of these regions
      coincides with a functional nuclear localization signal (NLS) of cHSF3 that was
      recognized by a nuclear transport receptor importin alpha. Point mutations of
      basic amino acids in the NLS inhibit both nuclear translocation and trimer
      formation of cHSF3. These results demonstrate that the NLS acts positively on the
      trimer formation of cHSF3 upon stress conditions.

PMID- 10942769
TI  - Nramp 2 (DCT1/DMT1) expressed at the plasma membrane transports iron and other
      divalent cations into a calcein-accessible cytoplasmic pool.
AB  - Nramp2, also known as DMT1 and DCT1, is a 12-transmembrane (TM) domain protein
      responsible for dietary iron uptake in the duodenum and iron acquisition from
      transferrin in peripheral tissues. Nramp2/DMT1 produces by alternative splicing
      two isoforms differing at their C terminus (isoforms I and II). The subcellular
      localization, mechanism of action, and destination of divalent cations
      transported by the two Nramp2 isoforms are not completely understood. Stable CHO
      transfectants expressing Nramp2 isoform II modified by addition of a hemaglutinin
      epitope in the loop defined by the TM7-TM8 interval were generated.
      Immunofluorescence with permeabilized and intact cells established that Nramp2
      isoform II is expressed at the plasma membrane and demonstrated the predicted
      extracytoplasmic location of the TM7-TM8 loop. Using the fluorescent, metal
      sensitive dye calcein, and a combination of membrane-permeant and -impermeant
      iron chelators, Nramp2 transport was measured and quantitated with respect to
      kinetic parameters and at steady state. Iron transport at the plasma membrane was
      time- and pH-dependent, saturable, and proportional to the amount of Nramp2
      expression. Iron uptake by Nramp2 at the plasma membrane was into the nonferritin
      bound, calcein-accessible so-called "labile iron pool." Ion selectivity
      experiments show that Nramp2 isoform II can also transport Co(2+) and Cd(2+) but
      not Mg(2+) into the calcein-accessible pool. Parallel experiments with
      transfectants expressing the lysosomal Nramp1 homolog do not show any divalent
      cation transport activity, establishing major functional differences between
      Nramp1 and Nramp2. Monitoring the effect of Nramp2 on the calcein-sensisitve
      labile iron pool allows a simple, rapid, and nonisotopic approach to the
      functional study of this protein.

PMID- 10942770
TI  - Regulation of transcription of the human presenilin-1 gene by ets transcription
      factors and the p53 protooncogene.
AB  - The expression of the human presenilin-1 cellular gene is suppressed by the p53
      protooncogene. The rapid kinetic of the down-regulation has suggested that it may
      result from a primary mechanism. We show here that p53 also suppresses the
      transcription of a presenilin-1 promoter-chloramphenicol acetyltransferase
      reporter synthetic gene in transient infection assays in neuroblastoma (SK-N-SH)
      and hepatoma (HepG2) cell lines. Only a minimum promoter including sequences from
      -35 to + 6 from the transcription initiation is sufficient to confer down
      regulation. We have previously defined a crucial DNA element controlling 90% of
      the expression of the gene within the same short area, and the identification of
      the transcription factors involved should also provide insights into the
      regulation of PS1 by p53. This region contains an Ets transcription factor
      binding motif, and a 2-base pair alteration within the core sequence (GGAA to
      TTAA) of the Ets consensus also reduced transcription by more than 90%. We now
      show that Ets1 and Ets2 indeed transactivate a PS1 promoter-chloramphenicol
      acetyltransferase reporter including the (-35 to +6) fragment. Furthermore, in
      vitro translated Ets2 binds specifically to the -10 Ets motif in electrophoretic
      mobility shift assays. Therefore, Ets1/2 factors bind specifically to the -10 Ets
      element and activate PS1 transcription. We also show that the coactivator p300
      enhances the activation by Ets1 and Ets2 as well as the repression by p53. p300
      is known to interact with p53 as well as with Ets1 and Ets2. We show that p53
      does not bind directly to the PS1 promoter. Hence the repression of PS1
      transcription by p53 is likely to be mediated through protein-protein
      interactions.

PMID- 10942771
TI  - Regulation of the human O(6)-methylguanine-DNA methyltransferase gene by
      transcriptional coactivators cAMP response element-binding protein-binding
      protein and p300.
AB  - O(6)-Methylguanine-DNA methyltransferase (MGMT)(1), a ubiquitous DNA repair
      protein, removes O(6)-alkylguanine from DNA, including cytotoxic O(6)
      chloroethylguanine induced by chemotherapeutic N-alkyl N-nitrosourea-type drugs,
      e.g. 1,3-bis(2-chloroethyl)-1-nitrosourea. Treating the pancreatic carcinoma cell
      line MIA PaCa-2 with trichostatin A (TSA), a specific inhibitor of histone
      deacetylase, increased MGMT mRNA and protein levels by 2-3-fold. Surprisingly,
      TSA treatment increased MGMT promoter-dependent luciferase activity by some 40
      fold in a transient reporter expression assay. Deletion and point mutation
      analysis showed that two AP-1 binding sites in the MGMT promoter are involved in
      activation by TSA. Ectopic expression of the transcriptional coactivators cAMP
      response element-binding protein-binding protein (CBP) and p300, which have
      intrinsic histone acetyltransferase activity, enhanced luciferase expression.
      Overexpression of adenovirus E1A, which binds CBP/p300, strongly inhibited both
      basal and TSA-inducible MGMT promoter activity, while a mutant E1A, defective in
      binding CBP/p300, did not. Chromatin immunoprecipitation assays revealed that TSA
      treatment increased histone acetylation in the endogenous MGMT promoter region,
      which also showed association with CBP/p300. Taken together, our results indicate
      that targeted histone acetylation results in the remodeling of chromatin by
      recruitment of the coactivator CBP/p300, and constitutes an important step in
      regulating MGMT expression.

PMID- 10942773
TI  - Rapid kinetics of regulator of G-protein signaling (RGS)-mediated Galphai and
      Galphao deactivation. Galpha specificity of RGS4 AND RGS7.
AB  - Regulator of G-protein signaling (RGS) proteins accelerate GTP hydrolysis by
      Galpha subunits speeding deactivation. Galpha deactivation kinetics mediated by
      RGS are too fast to be directly studied using conventional radiochemical methods.
      We describe a stopped-flow spectroscopic approach to visualize these rapid
      kinetics by measuring the intrinsic tryptophan fluorescence decrease of Galpha
      accompanying GTP hydrolysis and Galpha deactivation on the millisecond time
      scale. Basal k(cat) values for Galpha(o), Galpha(i1), and Galpha(i2) at 20
      degrees C were similar (0.025-0.033 s(-1)). Glutathione S-transferase fusion
      proteins containing RGS4 and an RGS7 box domain (amino acids 305-453) enhanced
      the rate of Galpha deactivation in a manner linear with RGS concentration. RGS4
      stimulated rates could be measured up to 5 s(-1) at 3 microm, giving a catalytic
      efficiency of 1.7-2.8 x 10(6) m(-1) s(-1) for all three Galpha subunits. In
      contrast, RGS7 showed catalytic efficiencies of 0.44, 0.10, and 0.02 x 10(6) m(
      1) s(-1) toward Galpha(o), Galpha(i2), and Galpha(i1), respectively. Thus RGS7 is
      a weaker GTPase activating protein than RGS4 toward all Galpha subunits tested,
      but it is specific for Galpha(o) over Galpha(i1) or Galpha(i2). Furthermore, the
      specificity of RGS7 for Galpha(o) does not depend on N- or C-terminal extensions
      or a Gbeta(5) subunit but resides in the RGS domain itself.

PMID- 10942772
TI  - Parkinson's disease-associated alpha-synuclein is more fibrillogenic than beta-
      and gamma-synuclein and cannot cross-seed its homologs.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically
      characterized by the presence of intracytoplasmic Lewy bodies. Recently, two
      point mutations in alpha-synuclein were found to be associated with familial PD,
      but as of yet no mutations have been described in the homologous genes beta- and
      gamma-synuclein. alpha-Synuclein forms the major fibrillar component of Lewy
      bodies, but these do not stain for beta- or gamma-synuclein. This result is very
      surprising, given the extent of sequence conservation and the high similarity in
      expression and subcellular localization, in particular between alpha- and beta
      synuclein. Here we compare in vitro fibrillogenesis of all three purified
      synucleins. We show that fresh solutions of alpha-, beta-, and gamma- synuclein
      show the same natively unfolded structure. While over time alpha-synuclein forms
      the previously described fibrils, no fibrils could be detected for beta- and
      gamma-synuclein under the same conditions. Most importantly, beta- and gamma
      synuclein could not be cross-seeded with alpha-synuclein fibrils. However, under
      conditions that drastically accelerate aggregation, gamma-synuclein can form
      fibrils with a lag phase roughly three times longer than alpha-synuclein. These
      results indicate that beta- and gamma-synuclein are intrinsically less
      fibrillogenic than alpha-synuclein and cannot form mixed fibrils with alpha
      synuclein, which may explain why they do not appear in the pathological hallmarks
      of PD, although they are closely related to alpha-synuclein and are also abundant
      in brain.

PMID- 10942774
TI  - Mammalian target of rapamycin-dependent phosphorylation of PHAS-I in four (S/T)P
      sites detected by phospho-specific antibodies.
AB  - The role and control of the four rapamycin-sensitive phosphorylation sites that
      govern the association of PHAS-I with the mRNA cap-binding protein, eukaryotic
      initiation factor 4E (eIF4E), were investigated by using newly developed phospho
      specific antibodies. Thr(P)-36/45 antibodies reacted with all three forms of PHAS
      I that were resolved when cell extracts were subjected to SDS-polyacrylamide gel
      electrophoresis. Thr(P)-69 antibodies bound the forms of intermediate and lowest
      mobility, and Ser(P)-64 antibodies reacted only with the lowest mobility form. A
      portion of PHAS-I that copurified with eIF4E reacted with Thr(P)-36/45 and Thr(P)
      69 antibodies but not with Ser(P)-64 antibodies. Insulin and/or amino acids
      increased, and rapamycin decreased, the reactivity of all three antibodies with
      PHAS-I in both HEK293 cells and 3T3-L1 adipocytes. Immunoprecipitated epitope
      tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also
      phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were
      incubated with the activating antibody, mTAb1. Interestingly, the phosphorylation
      of Thr-69 and Ser-64 was much more sensitive to inhibition by rapamycin-FKBP12
      than the phosphorylation of Thr-36/45, and the phosphorylation of Ser-64 by mTOR
      was facilitated by phosphorylation of Thr-36, Thr-45, and Thr-69. In these
      respects the phosphorylation of PHAS-I by mTOR in vitro resembles the ordered
      phosphorylation of PHAS-I in cells.

PMID- 10942775
TI  - Critical role of Smads and AP-1 complex in transforming growth factor-beta 
      dependent apoptosis.
AB  - Transforming growth factor-beta1 (TGF-beta1) induces not only cell growth
      inhibition but also apoptosis in hepatocytes, myeloid cells, and epithelial
      cells. Although Smad proteins are identified as key signal transducers in TGF
      beta1-dependent growth inhibition, their roles in the induction of apoptosis are
      unclear. We show here that both Smad proteins and AP-1 complex are involved in
      TGF-beta1 signaling for apoptosis. Overexpression of a dominant-negative Smad3
      mutant or Smad7, both of which impair Smad-mediated signal transduction, inhibits
      TGF-beta1-dependent apoptosis. Only the JunD. FosB form of the AP-1 complex is
      markedly activated during TGF-beta1-dependent apoptosis. FosB substantially
      enhances Smad3. Smad4-dependent transcription, and dominant-negative FosB blocks
      TGF-beta1-dependent apoptosis but not growth inhibition. Expression of JunD.FosB
      enhances induction of apoptosis by TGF-beta1. Moreover, JunD.FosB binds to the 12
      O-tetradecanoyl-13-acetate-responsive gene promoter element and recruits
      Smad3.Smad4 to form a multicomponent complex. These results suggest that Smad
      proteins and AP-1 complex synergize to mediate TGF-beta1-dependent apoptosis.

PMID- 10942776
TI  - Multiple ISWI ATPase complexes from xenopus laevis. Functional conservation of an
      ACF/CHRAC homolog.
AB  - The nucleosomal ATPase ISWI is the catalytic subunit of several protein complexes
      that either organize or perturb chromatin structure in vitro. This work reports
      the cloning and biochemical characterization of a Xenopus ISWI homolog.
      Surprisingly, whereas we find four complex forms of ISWI in egg extracts, we find
      no functional homolog of NURF. One of these complexes, xACF, consists of ISWI,
      Acf1, and a previously uncharacterized protein of 175 kDa. Like both ACF and
      CHRAC, this complex organizes randomly deposited histones into a regularly spaced
      array. The remaining three forms include two novel ISWI complexes distinct from
      known ISWI complexes plus a histone-dependent ATPase complex. This comprehensive
      biochemical characterization of ISWI underscores the evolutionary conservation of
      the ACF/CHRAC family.

PMID- 10942777
TI  - Dehydroaltenusin, a mammalian DNA polymerase alpha inhibitor.
AB  - Dehydroaltenusin was found to be an inhibitor of mammalian DNA polymerase alpha
      (pol alpha) in vitro. Surprisingly, among the polymerases and DNA metabolic
      enzymes tested, dehydroaltenusin inhibited only mammalian pol alpha.
      Dehydroaltenusin did not influence the activities of the other replicative DNA
      polymerases, such as delta and epsilon; it also showed no effect even on the pol
      alpha activity from another vertebrate (fish) or plant species. The inhibitory
      effect of dehydroaltenusin on mammalian pol alpha was dose-dependent, and 50%
      inhibition was observed at a concentration of 0.5 microm. Dehydroaltenusin
      induced inhibition of mammalian pol alpha activity was competitive with the
      template-primer and non-competitive with the dNTP substrate. BIAcore analysis
      demonstrated that dehydroaltenusin bound to the core domain of the largest
      subunit, p180, of mouse pol alpha, which has catalytic activity, but did not bind
      to the smallest subunit or the DNA primase p46 of mouse pol alpha. These results
      suggest that the dehydroaltenusin molecule competes with the template-primer
      molecule on its binding site of the catalytic domain of mammalian pol alpha,
      binds to the site, and simultaneously disturbs dNTP substrate incorporation into
      the template-primer.

PMID- 10942778
TI  - Antiproliferative properties of sphingosine 1-phosphate in human hepatic
      myofibroblasts. A cyclooxygenase-2 mediated pathway.
AB  - Proliferation of hepatic myofibroblasts (hMF) is central for the development of
      fibrosis during liver injury, and factors that may limit their growth are
      potential antifibrotic agents. Sphingosine 1-phosphate (S1P) is a bioactive
      sphingolipid with growth-regulating properties, either via Edg receptors or
      through intracellular actions. In this study, we examined the effects of S1P on
      the proliferation of human hMF. Human hMF expressed mRNAs for the S1P receptors
      Edg1, Edg3, and Edg5. These receptors were functional at nanomolar concentrations
      and coupled to pertussis toxin-sensitive and -insensitive G proteins, as
      demonstrated in guanosine 5'-3-O-(thio)triphosphate binding assays. S1P potently
      inhibited hMF growth (IC(50) = 1 microm), in a pertussis toxin-insensitive
      manner. Analysis of the mechanisms involved in growth inhibition revealed that
      S1P rapidly increased prostaglandin E(2) production and in turn cAMP, two growth
      inhibitory messengers for hMF; C(2)-ceramide and sphingosine, which inhibited hMF
      proliferation, did not affect cAMP levels. Production of cAMP by S1P was
      abolished by NS-398, a selective inhibitor of COX-2. Also, S1P potently induced
      COX-2 protein expression. Blocking COX-2 by NS-398 blunted the antiproliferative
      effect of S1P. We conclude that S1P inhibits proliferation of hMF, probably via
      an intracellular mechanism, through early COX-2-dependent release of
      prostaglandin E(2) and cAMP, and delayed COX-2 induction. Our results shed light
      on a novel role for S1P as a growth inhibitory mediator and point out its
      potential involvement in the negative regulation of liver fibrogenesis.

PMID- 10942780
TI  - Regulation by glucocorticoids of expression and activity of rBSC1, the Na+
      K+(NH4+)-2Cl- cotransporter of medullary thick ascending limb.
AB  - To assess whether glucocorticoids regulate rBSC1, the apical Na(+)-K(+)(NH(4)(+))
      2Cl(-) cotransporter of kidney medullary thick ascending limb (MTAL), studies
      were performed in normal rats, adrenalectomized (ADX) rats, and ADX rats infused
      with dexamethasone for 6 days. The effects of dexamethasone on rBSC1 were also
      studied in vitro using isolated rat MTAL segments. Cotransport activity was
      estimated by intracellular pH measurements; rBSC1 protein was quantified in MTAL
      crude membranes by immunoblotting analysis, and mRNA was quantified by
      quantitative reverse transcription-polymerase chain reaction. The abundance of
      rBSC1 protein and mRNA increased in ADX rats infused with dexamethasone compared
      with ADX rats (p < 0. 04). In addition, application of dexamethasone for 1-3 h to
      MTALs caused rBSC1 protein and mRNA abundance and cotransport activity to
      significantly increase in a hyperosmotic medium (450 mosmol/kg of H(2)O)
      containing 0.7 nm arginine vasopressin, which is an in vitro experimental
      condition that resembles the in vivo MTAL environment. Results obtained in
      various media and with 8-bromo-cAMP indicated that stimulation of rBSC1
      expression by glucocorticoids required interactions between glucocorticoid
      receptor- and cAMP-dependent factors. Up to 100 nm d-aldosterone had no effect on
      cotransport activity in vitro. Thus glucocorticoids directly stimulate MTAL rBSC1
      expression and activity, which contributes to glucocorticoid-dependent effects on
      the renal regulation of acid-base balance and urinary concentrating ability.

PMID- 10942779
TI  - Degradation of membrane-bound ganglioside GM1. Stimulation by
      bis(monoacylglycero)phosphate and the activator proteins SAP-B and GM2-AP.
AB  - According to our hypothesis (Furst, W., and Sandhoff, K. (1992) Biochim. Biophys.
      Acta 1126, 1-16) glycosphingolipids of the plasma membrane are digested after
      endocytosis as components of intraendosomal and intralysosomal vesicles and
      membrane structures. The lysosomal degradation of glycosphingolipids with short
      oligosaccharide chains by acid exohydrolases requires small, non-enzymatic
      cofactors, called sphingolipid activator proteins (SAPs). A total of five
      activator proteins have been identified as follows: namely the saposins SAP-A, 
      B, -C, and -D, which are derived from the single chain SAP-precursor protein
      (prosaposin), and the GM2 activator protein. A deficiency of prosaposin results
      in the storage of ceramide and sphingolipids with short oligosaccharide head
      groups. The loss of the GM2 activator protein blocks the degradation of the
      ganglioside GM2. The enzymatic hydrolysis of the ganglioside GM1 is catalyzed by
      beta-galactosidase, a water-soluble acid exohydrolase. The lack of ganglioside
      GM1 accumulation in patients suffering from either prosaposin or GM2 activator
      protein deficiency has led to the hypothesis that SAPs are not needed for the
      hydrolysis of the ganglioside GM1 in vivo. In this study we demonstrate that an
      activator protein is required for the enzymatic degradation of membrane-bound
      ganglioside GM1 and that both SAP-B and the GM2 activator protein significantly
      enhance the degradation of the ganglioside GM1 by acid beta-galactosidase in a
      liposomal, detergent-free assay system. These findings offer a possible
      explanation for the observation that no storage of the ganglioside GM1 has been
      observed in patients with either isolated prosaposin or isolated GM2 activator
      deficiency. We also demonstrate that anionic phospholipids such as
      bis(monoacylglycero)phosphate and phosphatidylinositol, which specifically occur
      in inner membranes of endosomes and in lysosomes, are essential for the activator
      stimulated hydrolysis of the ganglioside GM1. Assays utilizing surface plasmon
      resonance spectroscopy showed that bis(monoacylglycero)phosphate increases the
      binding of both beta-galactosidase and activator proteins to substrate-carrying
      membranes.

PMID- 10942781
TI  - An anti-oncogenic role for decorin. Down-regulation of ErbB2 leads to growth
      suppression and cytodifferentiation of mammary carcinoma cells.
AB  - The leucine-rich proteoglycan decorin interacts with the epidermal growth factor
      receptor and triggers a signaling pathway that leads to growth suppression. We
      find that decorin causes a functional inactivation of the oncogenic ErbB2 protein
      in breast carcinoma cells. Upon de novo expression of decorin, the ErbB2 protein
      is reduced by approximately 40%, whereas its degree of tyrosyl phosphorylation is
      almost completely abrogated. Both co-culture experiments or experiments with
      recombinant decorin demonstrate an initial induction of ErbB2 tyrosine kinase,
      followed by a profound and long-lasting down-regulation of its activity. This
      leads to growth inhibition and cytodifferentiation of mammary tumor cells and a
      concurrent suppression of their tumorigenic potential in vivo. These decorin
      mediated effects appear to involve the activation of ErbB4, which in turn would
      block the phosphorylation of heterodimers containing either ErbB2 or ErbB3. These
      results provide an explanation for the heightened decorin levels around invasive
      carcinomas and suggest that decorin may function as a natural antagonist of
      neoplastic cells enriched in ErbB2.

PMID- 10942782
TI  - Plasmin-mediated macrophage reversal of low density lipoprotein aggregation.
AB  - Evidence suggests that aggregated low density lipoprotein (AgLDL) accumulates in
      atherosclerotic lesions. Previously, we showed that AgLDL induces and enters
      surface-connected compartments (SCC) in human monocyte-derived macrophages by a
      process we have named patocytosis. Most AgLDL taken up by these macrophages in
      the absence of serum is stored in SCC and remains undegraded. We now show that
      macrophages released AgLDL (prepared by vortexing or treatment with phospholipase
      C or sphingomyelinase) from their SCC when exposed to 10% human lipoprotein
      deficient serum (LPDS). Macrophages also took up AgLDL in the presence of LPDS,
      but subsequently released it. In both cases, the released AgLDL was
      disaggregated. Although the AgLDL that macrophages took up could not pass through
      a 0.45-micrometer filter, >60% of AgLDL could pass this filter after release from
      the macrophages. Disaggregation of AgLDL was verified by gel-filtration
      chromatography and electron microscopy that also showed particles larger than
      LDL, reflecting fusion of LDL that aggregates. The factor in serum that mediated
      AgLDL release and disaggregation was plasmin generated from plasminogen by
      macrophage urokinase plasminogen activator. AgLDL release was decreased >90% by
      inhibitors of plasmin (epsilon-amino caproic acid and anti-plasminogen mAb), and
      also by inhibitors of urokinase plasminogen activator (plasminogen activator
      inhibitor-1 and anti-urokinase plasminogen activator mAb). Moreover, plasminogen
      could substitute for LPDS and produce similar macrophage release and
      disaggregation of AgLDL. Because only plasmin bound to the macrophage surface is
      protected from serum plasmin inhibitors, interaction of AgLDL with macrophages
      was necessary for reversal of its aggregation by LPDS. The released disaggregated
      LDL particles were competent to stimulate LDL receptor-mediated endocytosis in
      cultured fibroblasts. Macrophage-mediated disaggregation of aggregated and fused
      LDL is a mechanism for transforming LDL into lipoprotein structures size
      consistent with lipid particles found in atherosclerotic lesions.

PMID- 10942784
TI  - Mathematical modeling of mortality dynamics of mammalian populations exposed to
      radiation.
AB  - A mathematical model is developed which describes the dynamics of radiation
      induced mortality of a non-homogeneous (in radiosensitivity) mammalian
      population. It relates statistical biometric functions with statistical and
      dynamic characteristics of a critical system in organism of specimens composing
      this population. The model involves two types of distributions, the normal and
      the log-normal, of population specimens with respect to the radiosensitivity of
      the critical system cells. This approach suggests a new pathway in developing the
      methods of radiation risk assessment.

PMID- 10942783
TI  - Effects of treatment or/and vaccination on HIV transmission in homosexuals with
      genetic heterogeneity.
AB  - Several mutant genes in HIV co-receptors (e.g., CCR5, CCR2 and CXCR4) have been
      correlated with susceptibility to HIV or/and rate of progression to AIDS. Some of
      these genes have high allele frequencies in general populations. Their effects on
      the HIV/AIDS dynamics may be significant. To study such genetic heterogeneity,
      Hsu Schmitz [S.-F. Hsu Schmitz, A mathematical model of HIV transmission in
      homosexuals with genetic heterogeneity, J. Theoret. Med. (to appear)] proposed a
      one-sex model with susceptibles classified by genotype as having no, partial or
      full natural resistance to HIV infection and infecteds classified as rapid,
      normal or slow progressors. The example of CCR5-Delta32 mutation in San Francisco
      gay men indicated that the normal progressors are most responsible for disease
      spread. The per-partnership transmission rates of rapid and slow progressors are
      identified as key parameters. The present manuscript extends the previous one by
      considering the intervention of treatment or/and vaccination. Detailed
      investigations are illustrated by using the same example of CCR5-Delta32 mutation
      in San Francisco gay men. Treating only newly infected individuals or vaccinating
      only newly recruited susceptibles is not effective enough for disease control.
      When both measures are applied, the epidemic may be eradicated if the
      transmission rate of slow progressors is not too large, and treatments and
      vaccines in use are of decent quality.

PMID- 10942785
TI  - Estimation of HIV infection and incubation via state space models.
AB  - By using the state space model (Kalman filter model) of the HIV epidemic, in this
      paper we have developed a general Bayesian procedure to estimate simultaneously
      the HIV infection distribution, the HIV incubation distribution, the numbers of
      susceptible people, infective people and AIDS cases. The basic approach is to use
      the Gibbs sampling method combined with the weighted bootstrap method. We have
      applied this method to the San Francisco AIDS incidence data from January 1981 to
      December 1992. The results show clearly that both the probability density
      function of the HIV infection and the probability density function of the HIV
      incubation are curves with two peaks. The results of the HIV infection
      distribution are clearly consistent with the finding by Tan et al. [W.Y. Tan,
      S.C. Tang, S.R. Lee, Estimation of HIV seroconversion and effects of age in San
      Francisco homosexual populations, J. Appl. Stat. 25 (1998) 85]. The results of
      HIV incubation distribution seem to confirm the staged model used by Satten and
      Longini [G. Satten, I. Longini, Markov chain with measurement error: estimating
      the 'true' course of marker of the progression of human immunodeficiency virus
      disease, Appl. Stat. 45 (1996) 275].

PMID- 10942786
TI  - Influence of vertical and mechanical transmission on the dynamics of dengue
      disease.
AB  - We formulate a non-linear system of differential equations that models the
      dynamics of transmission of dengue fever. We consider vertical and mechanical
      transmission in the vector population, and study the effects that they have on
      the dynamics of the disease. A qualitative analysis as well as some numerical
      examples are given for the model.

PMID- 10942787
TI  - An intuitive formulation for the reproductive number for the spread of diseases
      in heterogeneous populations.
AB  - The thresholds for mathematical epidemiology models specify the critical
      conditions for an epidemic to grow or die out. The reproductive number can
      provide significant insight into the transmission dynamics of a disease and can
      guide strategies to control its spread. We define the mean number of contacts,
      the mean duration of infection, and the mean transmission probability
      appropriately for certain epidemiological models, and construct a simplified
      formulation of the reproductive number as the product of these quantities. When
      the spread of the epidemic depends strongly upon the heterogeneity of the
      populations, the epidemiological models must account for this heterogeneity, and
      the expressions for the reproductive number become correspondingly more complex.
      We formulate several models with different heterogeneous structures and
      demonstrate how to define the mean quantities for an explicit expression for the
      reproductive number. In complex heterogeneous models, it seems necessary to
      define the reproductive number for each structured subgroup or cohort and then
      use the average of these reproductive numbers weighted by their heterogeneity to
      estimate the reproductive number for the total population.

PMID- 10942788
TI  - The role of the t-PA I/D and PAI-1 4G/5G polymorphisms in African-American adults
      with a diagnosis of myocardial infarction or venous thromboembolism.
AB  - To determine whether or not the PAI-1 4G/5G and t-PA I/D polymorphisms in African
      Americans were linked to cardiovascular disease, the association of these
      polymorphisms to disease expression was analyzed in a recently completed case
      control study of myocardial infarction or venous thromboembolism among African
      Americans. All African-Americans patients with a history of venous
      thromboembolism attending an anticoagulant clinic, and patients with a history of
      a MI attending a cardiology clinic at a large local urban public hospital were
      eligible for inclusion as cases in the study. In this study it was observed that
      there was a statistically significant association between the D allele of the t
      PA I/D polymorphism and venous thromboembolism and a nonsignificant association
      between the D allele and myocardial infarction among African-Americans. t-PA
      antigen levels were statistically significantly higher among both myocardial
      infarction and venous thromboembolism cases compared with control subjects. The
      genotypes were unrelated to t-PA plasma levels. There was no association between
      either myocardial infarction or venous thromboembolism and the 4G/5G PAI-1
      genotype. It was also found that genotype frequencies for both PAI-1 4G/5G and t
      PA I/D polymorphisms in African-American adults were different from those
      reported for both U.S. Causcians and Europeans.

PMID- 10942789
TI  - Atipamezole, an imidazoline-type alpha(2)-adrenoceptor inhibitor, binds to human
      platelets and inhibits their adrenaline-induced aggregation more effectively than
      yohimbine.
AB  - To investigate the usefulness of atipamezole [MPV-1248, 4-(2-ethyl-2, 3-dihydro
      1H-inden-2-yl)-1H-imidazole], a novel alpha(2)-adrenoceptor-specific antagonist,
      as a tool in platelet studies, the ability of this antagonist: (1) to bind to
      platelet alpha(2)-adrenoceptors, and (2) to inhibit adrenaline-induced platelet
      aggregation was compared to that of yohimbine, another commonly used alpha(2)
      adrenoceptor antagonist. It was found that atipamezole binds to platelet alpha(2)
      adrenoceptors more effectively than yohimbine: [3H]atipamezole has more than
      three times higher alpha(2)-adrenoceptor binding affinity in intact gel-filtered
      human platelets (equilibrium dissociation constant (K(d)) 0.7+/-0.21 vs. 2.9+/
      0.77 nM, p<0.05), but only one-third of the binding capacity of [3H]yohimbine
      (B(max) 27.0+/-3.8 vs. 100+/-19 pM/10(5) cells, p<0.01). Functionally, in
      comparison with yohimbine, an almost threefold lower concentration of atipamezole
      inhibited adrenaline (5 microM)-induced platelet aggregation. A concentration of
      atipamezole, which inhibited this aggregation by 50% (IC(50)), was 0.37+/-0.07
      microM, whereas IC(50) for yohimbine was 0.98+/-0.12 microM, p<0.0001. Thus,
      atipamezole represents a functionally undisputed alpha(2)-adrenoceptor
      antagonist, more effective than yohimbine. Its distinct binding profile as a
      radioligand also suggests the presence of imidazol(in)e binding sites in
      platelets.

PMID- 10942790
TI  - Molecular cloning of glycoprotein Ib-binding protein, flavocetin-A, which
      inhibits platelet aggregation.
AB  - Flavocetin-A is a strong platelet aggregation inhibitor isolated from the venom
      of Trimeresurus flavoviridis. It binds specifically to platelet glycoprotein Ib
      with high affinity and inhibits von Willebrand factor-dependent platelet
      aggregation. The apparent molecular weight of flavocetin-A is 149 kDa. It
      consists of two subunits, alpha (17 kDa) and beta (14 kDa). The amino acid
      sequences of the alpha and beta subunits were determined from cloned cDNAs.
      Deduced amino acid sequences showed signal peptide-sequences of 23 amino acids
      for both alpha and beta subunits, mature peptide sequences of 135 amino acids for
      the alpha subunit, and 125 amino acids for the beta subunit. The amino acid
      sequences of alpha and beta subunits show high degrees of homology to those of C
      type lectin-like venom proteins such as habu coagulation factors IX/X-binding
      protein (IX/X-bp), botrocetin, and alboaggregin-B. The cysteinyl residues of
      flavocetin-A, IX/X-bp, and botrocetin are conserved, except that flavocetin-A
      contains Cys 135 in the alpha subunit and Cys 3 in the beta subunit. We assumed
      that the arrangements of disulfide bridges in flavocetin-A are similar to those
      of IX/X-bp and botrocetin, and the additional Cys 135 of the alpha subunit and
      Cys 3 of the beta subunit are involved in novel disulfide bridges. These findings
      suggested that the additional disulfide bridges formed with Cys 135 of the alpha
      subunit and Cys 3 of the beta subunit cause polymerization of C-type lectin-like
      heterodimers.

PMID- 10942791
TI  - Antiplatelet activity of Staphylococcus aureus lipoteichoic acid is mediated
      through a cyclic AMP pathway.
AB  - In this study, Gram-positive Staphylococcus aureus lipoteichoic acid (LTA) dose
      dependently (0.1-1.0 microg/mL) and time dependently (10-60 min) inhibited
      platelet aggregation in human platelets stimulated by agonists (i.e., thrombin
      and collagen). LTA also dose dependently inhibited intracellular Ca(2+)
      mobilization in human platelets stimulated by collagen. In addition, LTA (0.5 and
      1.0 microg/mL) dose dependently increased the formation of cyclic AMP but not
      cyclic GMP in platelets. LTA (0.5 and 1.0 microg/mL) did not significantly
      increase the production of nitrate within a 10-min incubation period. Rapid
      phosphorylation of a platelet protein of M(r) 47,000, a marker of protein kinase
      C activation, was triggered by PDBu (0.03 microM). This phosphorylation was dose
      dependently inhibited by LTA (0.5 and 1.0 microg/mL) within a 10-min incubation
      period. Furthermore, LTA (0.5 and 1.0 microg/mL) also inhibited platelet
      aggregation induced by PDBu (0.03 microM) in human platelets. These results
      indicate that the antiplatelet activity of LTA may be involved in the increase of
      cyclic AMP, leading to inhibition of intracellular Ca(2+) mobilization and
      protein kinase C activity. Therefore, LTA-mediated alteration of platelet
      function may contribute to bleeding diathesis in septicemic and endotoxemic
      patients.

PMID- 10942793
TI  - Protease nexin-2/Amyloid beta-protein precursor regulates factor VIIa and the
      factor VIIa-tissue factor complex.
AB  - Protease nexin-2/amyloid beta-protein precursor (PN-2/AbetaPP) and its Kunitz
      protease inhibitory (KPI) domain were characterized as inhibitors of factor VIIa
      (FVIIa) and factor VIIa-tissue factor complex (FVIIa-TF). PN-2/AbetaPP and KPI
      domain inhibited FVIIa with an apparent K(i) of 1.1+/-0.2x 10(-7) M and 1.5+/
      0.1x10(-7) M, respectively. When soluble tissue factor (TF(1-219)) was present,
      there was increased FVIIa inhibition by PN-2/AbetaPP or KPI domain (K(i)=7.8+/
      0.3x10(-8) M and 6.8+/-0.6x10(-8) M, respectively). When relipidated tissue
      factor (TF(1-243)) was present, the K(i) of FVIIa inhibition by PN-2/AbetaPP
      increased 4.7-fold further. PN-2/AbetaPP complexed with FVIIa, as shown on gel
      filtration and solid phase binding assay. The apparent second-order rate constant
      of inhibition of FVIIa by PN-2/AbetaPP in the absence of TF(1-219) was less than
      that of the FVIIa-TF(1-219) complex. Antithrombin in the absence of TF(1-219)
      also had a lower apparent second-order rate constant of inhibition than in its
      presence. In a mixture that included FVIIa, relipidated TF(1-243) and factor X,
      PN-2/AbetaPP or KPI domain had an IC(50) at 65 and 250 nM, respectively;
      antithrombin and heparin (1 U/mL) had an IC(50) of 12.8 nM. These data indicate
      that tissue factor promoted the inhibition of FVIIa by PN-2/AbetaPP or KPI
      domain, but antithrombin was a better inhibitor of soluble FVIIa-TF in extrinsic
      tenase.

PMID- 10942794
TI  - Determination of the N-terminal amino acid sequence of the purified prothrombin
      from a patient with liver cirrhosis.
AB  - The reasons for the decreased functional activity of prothrombin in liver
      diseases are still speculative. When a highly purified preparation of prothrombin
      from a patient with liver cirrhosis is available, the cause of prothrombin
      abnormalities may be researched on a molecular basis. In this study, prothrombin
      (6.7 mg) was purified from the ascites fluid (1130 mL) of a patient with liver
      cirrhosis by barium citrate adsorption, ammonium sulfate elution, DEAE Sephacel
      and Heparin Sepharose CL-6B column chromatography steps. The molecular weight of
      this prothrombin was the same as that of normal prothrombin purified from a
      normal plasma pool. The specific activities were found to be 3.36 U/mg in the one
      stage clotting assay and 28.9 U/mg in the staphylocoagulase/chromogenic substrate
      assay, while the normal prothrombin specific activities were 3.92 U/mg and 30.1
      U/mg respectively. When N-terminal amino acid sequence analysis was carried out,
      it was seen that the first 20 residues were identical to the normal human
      prothrombin excepting the Gla at position #14.

PMID- 10942792
TI  - Sphingosine 1-phosphate stimulates G(i)- and Rho-mediated vascular endothelial
      cell spreading and migration.
AB  - Sphingosine 1-phosphate (Sph-1-P) is a bioactive lipid released from activated
      platelets, which may be involved in angiogenesis. We, hence, investigated Sph-1-P
      effects on human umbilical vein endothelial cells (HUVECs) from a viewpoint of
      angiogenesis. Sph-1-P facilitated HUVEC spreading on the basement membrane
      component Matrigel, at concentrations ranging from 10 to 250 nM. This stimulatory
      response induced by Sph-1-P was blocked by pertussis toxin and C3 transferase
      (from Clostridium botulinum), which inactivate G(i)-type heterotrimeric G protein
      and Rho, respectively. Furthermore, Sph-1-P, in the modified Boyden's chamber
      assay, stimulated HUVEC migration in a concentration-dependent manner, up to 250
      nM. Checkerboard analysis revealed that Sph-1-P markedly induces directional
      migration (chemotaxis), but a random motility (chemokinesis) was also enhanced.
      The stimulatory effect of Sph-1-P on HUVEC migration was much stronger than that
      of other bioactive lipids, and again inhibited by pertussis toxin and by C3
      transferase. Our present results that Sph-1-P induces endothelial spreading and
      migration through G(i)-coupled cell surface receptor(s) and Rho are consistent
      with a recent report on the role of this platelet-derived sphingolipid as a novel
      regulator of angiogenesis.

PMID- 10942795
TI  - Intrinsic coagulation pathway: an activation threshold.
AB  - The activation threshold for the intrinsic pathway of coagulation was
      experimentally determined in stirred recalcified plasma from the dependence of
      plasma clotting time after activation by celite. Concentration of factor XIa was
      used as a measure of activation. At free calcium concentrations below 0.45 mM,
      plasma clotting time depended nonlinearly on the factor XIa concentration: with
      decreasing concentration of factor XIa (or celite), the clotting time
      dramatically increased until no coagulation was observed at concentrations of
      factor XIa below the threshold. As the free calcium concentration increased, the
      threshold concentration of factor XIa sharply decreased, from 30 pM at 0.35 mM
      free calcium to less than 3 pM at 0.45 mM. In the range of free calcium
      concentrations from 0.45 mM to physiologic ones, plasma coagulated even in the
      absence of celite in plastic cuvettes. This fact and extremely low threshold
      concentrations of factor XI (on the order of 0.5 pM) preclude determining the
      factor XI threshold at physiologic free calcium. As factor XIa is localized to
      the activating surfaces, observing the local surface concentrations of factor XIa
      and the dynamics of fibrin formation in systems without stirring may solve the
      problem.

PMID- 10942797
TI  - Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic
      implications in osteosarcoma and Ewing sarcoma.
AB  - We examined alterations of the p16INK4, p14ARF, p15, TP53, and MDM2 genes in 30
      osteosarcomas and 24 Ewing sarcomas. Among 21 osteosarcomas and 24 Ewing
      sarcomas, p16INK4, p14ARF, and p15 abnormalities were found in 4 (19%), 2 (9%),
      and 3 (14%) osteosarcomas, respectively, and in 4 (17%), 3 (13%), and 4 (17%)
      Ewing sarcomas, respectively. The alterations of p16INK4, p14ARF, and p15
      included homozygous deletions spanning all 3 genes, methylation of p16INK4 or
      p15, and a nonsense mutation of p16INK4, which simultaneously caused a missense
      mutation of p14ARF. Alterations of TP53 were found in 15 (50%) of 30
      osteosarcomas and 1 (3%) of 24 Ewing sarcomas. None of the sarcomas showed MDM2
      amplification. While TP53 abnormalities were far more frequent in osteosarcoma
      than in Ewing sarcoma, alterations of p16INK4, p14ARF, and p15 were present at
      similar frequencies in the two types of sarcoma. The event-free survival (EFS)
      was worse in Ewing sarcoma patients with p16INK4 and p14ARF mutation/deletion
      than in those without the mutation/deletion (P = 0.019), and EFS was worse in
      osteosarcoma patients with TP53 alterations than in those without TP53
      alterations (P = 0.048). The different incidence of TP53 abnormalities in the 2
      types of sarcoma may reflect differences of the molecular processes through which
      the 2 types of tumor develop.

PMID- 10942796
TI  - Experimental thrombosis I: relation with fibrinogen and other haemostatic
      parameters.
AB  - Epidemiological studies have shown that the haemostatic parameters Fibrinogen
      (Fg), Factor VII (F VII), Factor VIII (F VIII), von Willebrand factor (vWF),
      Tissue Plasminogen Activator (t-PA), Plasminogen Activator Inhibitors (PAI) are
      risk factors/markers of ischemic cardiovascular disease. Ferritin (sFER) and
      Leukocytosis have also been implicated. In the present study we have followed the
      levels of fibrinogen, von Willebrand factor and thrombomodulin in relation to
      lipids, iron and the appearance of atherosclerotic lesions in New Zealand rabbits
      fed with a cholesterol enriched diet for a two-month period compared with a group
      of control rabbits. Hematocrit and white blood cell count (WBC) were measured in
      parallel. In hyperchlesterolemic rabbits the levels of fibrinogen and von
      Willebrand factor increased progressively, showing a positive correlation with
      the increasing cholesterol levels. There was an increase in soluble
      thrombomodulin beginning at the eighth week of study. In addition, these animals
      showed gross intimal atherosclerotic lesions in the whole extension of their
      aortas. Immunohistochemical studies showed the presence of fibrin(ogen) related
      antigen throughout the arterial wall and in the central portions of the
      atheromas. In the control group there was no formation of atherosclerotic plaques
      and all haemostatic, haematological and biochemical parameters were within the
      normal range. WBC and sFER levels were unaffected in both groups. Our results
      show that increased levels of fibrinogen and von Willebrand factor, known
      coronary risk factors, are strongly associated with the formation of
      atherosclerotic plaques in rabbits. The plaques contain a considerable amount of
      fibrinogen related antigen.

PMID- 10942798
TI  - Fluorescence in situ hybridization detection of two telomeres on the short arm of
      a derived chromosome 16 in an infant with thrombocytopenia.
AB  - We report a case of severe thrombocytopenia with an abnormal bone marrow
      karyotype described by G-banding analysis as t(16;21)(p?13;q11). Using
      fluorescence in situ hybridization (FISH) analysis with whole chromosome paints,
      the chromosome rearrangement was shown to be more complex, with the additional
      cryptic involvement of the long arm of chromosome 3. The chromosome rearrangement
      involved the breakpoints 3q26, 16p13.3, and 21q11; this rearrangement has not
      been previously described. The size of genomic material translocated from the
      chromosome 16 homologue was too small to be detected by chromosome paint. A 16p
      specific telomeric probe was hybridized to locate the translocated 16p material.
      The 16p telomeric unique sequence DNA was retained on the der(16) chromosome,
      indicating a more distal breakpoint. This study demonstrates that telomeric
      translocations can occur that would be undetected by telomeric-specific FISH
      probes.

PMID- 10942799
TI  - Apparently unrelated clones shown by spectral karyotyping to represent clonal
      evolution of cryptic t(10;11)(p13;q23) in a patient with acute monoblastic
      leukemia.
AB  - The accurate genetic classification of acute leukemia is of the utmost clinical
      importance for treatment stratification. In the present study, we report on a
      young girl with aggressive acute monoblastic leukemia (AML) (M5b) with skin,
      lymph node, and bone marrow involvement, in whom cytogenetic analysis revealed
      three clones with different secondary chromosomal changes. Two clones had the
      secondary +8 and del(9q) aberrations, with the der(11)t(1;11) in the second one;
      the third clone was apparently unrelated to the others, and had add(7)(p?21),
      13,+22. Using the spectral karyotyping (SKY) technique, we found that all three
      clones originated from a common clone that harbored the hidden primary
      t(10;11)(p13;q23) or its derivatives, suggesting clonal evolution. The first
      clone had the balanced t(10;11), the second had its derivative, der(10)t(10;11),
      and the third had the other derivative, der(11)t(10;11). On fluorescence in situ
      hybridization (FISH), MLL gene splitting, with translocation of its centromeric
      portion to 10p, and deletion of its telomeric portion, was demonstrated. In
      conclusion, the detection of the very poor prognostic t(10;11) aberration in AML,
      was possible by complementing the traditional cytogenetic analysis with SKY and
      FISH.

PMID- 10942800
TI  - Loss of 14q and 22q in gastrointestinal stromal tumors (pacemaker cell tumors).
AB  - Gastrointestinal stromal tumors (GISTs), also referred to as "gastrointestinal
      pacemaker cell tumors (GIPACT)" are mesenchymal neoplasms that are phenotypically
      similar to the interstitial cells of Cajal (ICC). Cytogenetic studies of this
      entity are rare and molecular cytogenetic studies utilizing chromosome-specific
      probes are nonexistent. In the current study, cytogenetic and molecular
      cytogenetic analysis of 12 histologically and immunohistochemically confirmed
      GISTs revealed loss of a whole chromosome 14 or region(s) of 14q in 8 tumors
      evaluated (67%) and loss of a whole chromosome 22 or region(s) of 22q in 8 (67%)
      patients. Loss of 14q and 22q were observed in histologically benign and
      malignant GISTs. Structural rearrangements of chromosome 1 were observed in 2
      malignant GISTs. These findings indicate that loss of 14q and 22q are nonrandom,
      early events in GIST tumorigenesis and suggest that tumor suppressor genes
      responsible for the development of this neoplasm may be located on these
      chromosomal arms.

PMID- 10942801
TI  - Stepwise genetic changes associated with progression of nontumorigenic HPV-18
      immortalized human prostate cancer-derived cell line to a malignant phenotype.
AB  - Cytogenetics, fluorescence in situ hybridization (FISH), and comparative genomic
      hybridization (CGH) were used to identify genes that are involved in the
      development and progression of prostate cancer. For that purpose, we chose a cell
      line established in vitro from a prostatic adenocarcinoma which was
      nontumorigenic in nude mice and followed its progression to a tumorigenic cell
      line. Stepwise changes were observed in the cell line as it became tumorigenic.
      The composite karyotype at the nontumorigenic stage (CA-HPV-10) was 68
      approximately 77,XXY,-(1, 9, 13, 14, 19, 22),+(4, 5, 11, 18, 20, 21),+(del(1)
      (q23q31)=M1 (two copies), +der(9)t(1;9)(q24 approximately q31;p23)=M5(two
      copies), der(14)t(14;?)(q10;?)=M17 in the majority of metaphases. These two
      derivative chromosomes were also observed a previous study. Our CGH analysis
      clearly showed that this deleted region in M1 is, in fact, translocated with
      derivative M5 and, in reality, is amplified. The cell line established from
      nodule (SCID 5019 p11), showed a number of new changes, as described; however,
      the most significant change was amplification of the 8q23 approximately qter
      region, harboring c-myc. This region was translocated with chromosomes 2, 4, and
      16 as der(2)t(2;8)(q33;q23)=M12, der(4)t(4;8)(q34;q23)=M11, and
      der(16)t(8;16)(q24;q21)=M9. We deduce from our study that amplification of c-myc
      and other genes in the 8q23 approximately qter region were important in
      progression but did not lead to tumorigenicity. The population that became
      tumorigenic (SCID 5019 II) showed almost all of the same changes in the karyotype
      as observed in the nodular cell line; the only significant change was the
      appearance of der(11)t(4;11)(q32;q22)=M7 and the addition of another copy of
      t(3q;7p)=M2. These new changes lead to loss of chromosomes 3p, 4pter
      approximately q34, 6, 7q21 approximately qter, 11q22 approximately qter, and 18q,
      and gain of 3q, 7p, 8q23 approximately qter, and 11pter approximately q22, before
      the cell line became tumorigenic. The clonal selection of the population is
      proven by the presence of a number of the same derivative chromosomes in both the
      nodular and tumorigenic cell line. As it progressed to tumorigenicity, some of
      the same changes observed in the original study re-appear at different stages of
      malignancy, although it was absent in the nontumorigenic cell line. These are:
      der(16)t(8;16)(q24;q21)=M9 in the nodular cell line and
      der(11)t(4;11)(q32;q22)=M7 in the tumorigenic cell line. In our system,
      amplification of c-myc and other genes in der(2)t(2;8)(q33;q23)=M12,der(4)
      t(4;8)(q34;q23)=M11 together with the presence of der(16)t(8;16)(q24;q21)=M9 and
      der(11)t(4;11)(q32;q22)=M5 makes the cell line tumorigenic. It is either
      nontumorigenic, with the presence of a marker equivalent to der(16)=M9 and
      der(11)=M7 observed in the original study, and only nodular (SCID 5019 p11,
      present study), with the presence of number of markers with c-myc amplification
      (M9, M11, and M12). There is accumulation of all the above-mentioned changes in
      the same cell before it becomes tumorigenic.

PMID- 10942803
TI  - Cytogenetic studies in patients with mastocytosis.
AB  - Chromosomal aberrations in hematopoietic cells are common in malignant
      hematological disorders and have also been reported in some patients with
      mastocytosis. In this study, 34 patients with either urticaria pigmentosa or
      systemic mastocytosis were investigated by cytogenetic analysis of bone marrow
      cells. A follow-up investigation was performed in 22 patients. Clones with
      chromosome abnormalities were found in 32% of the patients at the first
      examination and in 27% at the second examination; in total, 41% of the patients
      had an abnormal clone in at least one examination. No clinical correlation was
      found with regard to cytogenetic results, with the exception of four patients who
      had an associated hematological disease and poor prognosis. In the second
      examination, only 6 patients had an unchanged chromosome pattern, and 4 of the
      patients with an initial normal pattern had appearance of abnormal clones;
      however, in 7 patients, the initial abnormal cells disappeared. The abnormalities
      were, among others, deletions of chromosomes 5, 7, 11, and 20. The proportion of
      cells with structural or numerical chromosome changes was higher in comparison
      with reported control groups. The frequency and type of chromosome abnormalities
      in bone marrow cells from patients with mastocytosis was about the same as
      observed in other chronic myeloproliferative disorders and myelodysplastic
      syndromes, diseases which also developed in 4 of our patients. An association
      between malignant hematological disorders and mastocytosis have been suggested by
      us and others. The chromosome abnormalities maybe reflect a genetic instability
      of the hematopoietic cells in mastocytosis.

PMID- 10942802
TI  - Clonal chromosome abnormalities in enchondromas and chondrosarcomas.
AB  - We report cytogenetic findings in short-term cell cultures from five enchondromas
      and four chondrosarcomas. Clonal chromosome aberrations were found in one case of
      enchondroma, and in all cases of chondrosarcoma. The only enchondroma with
      nonrandom abnormalities had a reciprocal t(8;17)(q23;p13), and monosomies 9, 19,
      and/or 22. In contrast to the few karyotypic findings in one of five
      enchondromas, the four chondrosarcomas were commonly characterized by cytogenetic
      heterogeneity, with a tendency for increasing karyotypic complexity in higher
      grade tumors. Two cases, one grade III and one metastasizing grade II
      chondrosarcoma, revealed hypodiploid stem- and sidelines with loss of chromosomes
      6, 10, 13, 14, and 22, as common chromosomal abnormalities, suggesting a distinct
      karyotypic pattern in a subset of biologically aggressive chondrosarcomas.

PMID- 10942804
TI  - Simultaneous presence of t(2;8)(p12;q24) and t(14;18)(q32;q21) in a B-cell
      lymphoproliferative disorder with features suggestive of an aggressive variant of
      splenic marginal-zone lymphoma.
AB  - We report a case of an aggressive variant of splenic marginal-zone lymphona
      (SMZL) with circulating villous lymphocytes. The karyotype of all examined cells
      had multiple structural and numerical abnormalities, including two lymphoma
      characteristic translocations, t(2;8)(p12;q24) and t(14;18)(q32;q21). Based on a
      literature review of cytogenetic aberrations of splenic lymphoma with villous
      lymphocytes (SLVL) and SMZL, this is apparently the first documentation of these
      two translocations in a case of SMZL, and could reflect the heterogeneity of the
      disorder.

PMID- 10942805
TI  - Trisomy 10 in acute myeloid leukemia. Three additional cases from the database of
      the Japan Adult Leukemia Study Group (JALSG) AML-92 and AML-95.
AB  - To clarify the clinical and hematologic features of a rare numerical chromosome
      abnormality, we searched for trisomy 10 in acute myelogenous leukemias (AMLs)
      using the database of the Japan Adult Leukemia Study Group (JALSG) AML 92 and 95.
      Among the sequentially registered patients of JALSG-AML 92 (655 patients) and
      JALSG-AML 95 (531 patients), chromosome results were obtained in 1,074 patients
      (90.6%), and we found 3 patients with trisomy 10 as a sole abnormality. The first
      patient had an AML-M1 morphology with CD7 antigen; the patient obtained complete
      remission (CR) with the first course of chemotherapy. The second patient had an
      AML-M1 morphology without expressing CD7 antigen; this patient obtained CR, but
      relapsed 3 months later, and underwent allogeneic bone marrow transplantation. He
      suffered from chronic graft-versus-host disease and expired 38 months after the
      AML diagnosis. The third patient had AML-M0 with CD7 positivity. He obtained CR;
      however, brain abscess and cerebral hemorrhage occurred. In the literature, the
      mean age of patients with trisomy 10 AML is 57.8 years, the gender ratio is M/F =
      1.5, and the frequency of M0/M1/M2 is 85.7%. A high incidence (81. 8%) of CD7
      expression of leukemia cells is notable. About 73% of patients survived for
      greater than 12 months.

PMID- 10942806
TI  - Association of t(9;11)-MLL AF9 and trisomy 8 in an AML-M5 preceded by
      pancytopenia.
AB  - The implication of MLL gene rearrangements in the prognosis of acute myeloblastic
      leukemia is an issue of considerable current interest. We report a case of a
      young man who initially presented with a pancytopenia and went on to develop a
      highly-aggressive acute myeloblastic leukemia. At this time, the karyotypic study
      revealed trisomy 8, a t(9;11) was demonstrated by fluorescence in situ
      hybridization (FISH) and the MLL/AF4 rearrangement by reverse transcriptase
      polymerase chain reaction (RT-PCR).

PMID- 10942807
TI  - Numerical chromosomal changes in metastatic prostate cancer following anti
      androgen therapy: fluorescence in situ hybridization analysis of 5 Japanese
      cases.
AB  - We used fluorescence in situ hybridization with centromere-specific probes for
      chromosomes 7, 8, 10, and Y to determine the copy number of these chromosomes in
      metastatic prostate cancers of five Japanese cases. Freshly prepared samples were
      obtained from prostate needle biopsies at different phases of clinical treatment;
      pretreatment, 1 week, 4 weeks, 12 weeks, 24 weeks post-treatment (PT), and
      clinical relapse. Gain of chromosomes 7 and 8, as noted in pretreatment samples;
      however, in post-treatment specimens (four of five cases), a remarkable reduction
      in the number of cells with extra copies of these chromosomes was detected. This
      decrease in the number of cells with additional chromosome 7 and 8 signals was
      correlated with the clinicohistopathological findings until 4 weeks PT.
      Chromosomes Y and 10 did not show numerical aberrations before treatment or
      changes in cells with aneusomy after treatment in all five cases. Our results
      suggest that gains of chromosomes 7 and 8 correlate with high grade and stage,
      and that changes in the cell number with aneusomy of chromosomes 7 and 8 reflect
      the clinical effects of anti-androgen therapy at an early phase, which may also
      indicate the androgen dependency of prostate cancer cells.

PMID- 10942808
TI  - The "Atlas of genetics and cytogenetics in oncology and haematology" on the
      internet and a review on infant leukemias.
AB  - The "Atlas of Genetics and Cytogenetics in Oncology and Haematology" (URL:
      http://www.infobiogen.fr/services/chromcancer) is a database devoted to
      chromosome abnormalities in cancer, cancer-prone diseases, and genes involved in
      cancer. The information is concise and updated. This database is made for and by
      cytogeneticists, molecular biologists, clinicians in oncology and hematology, and
      pathologists, who are encouraged to contribute. The database is herein presented,
      together with an example concerning congenital leukemias.

PMID- 10942809
TI  - A t(1;22)(p13;q13) in four children with acute megakaryoblastic leukemia (M7),
      two with Down syndrome.
AB  - We report four children with acute megakaryoblastic leukemia (AML-M7) and
      t(1;22)(p13;q13), two of them with Down syndrome; their ages were 7 months, and
      6, 7, and 10 years. These findings differ from those reported in children with M7
      and t(1;22) at the age of presentation (exclusively under 1-year-old) and in the
      two cases associated with Down syndrome (t[1;22],+21c) that may be due to the
      high heterogeneity of the chromosomal changes in children with AML. We cannot
      disregard ethnic difference distribution of chromosomal changes and age of
      presentation in Mexican children with AML.

PMID- 10942810
TI  - Trisomy/ tetrasomy of chromosome 8 and +i(8q) as the sole chromosome abnormality
      in three adult patients with myelomonocytic leukemia.
AB  - We report three cases of tetrasomy 8 associated with myeloid disease. Two
      patients had chronic myelomonocytic leukemia (CMMoL) and the other had acute
      monocytic leukemia (AML M5 FAB). Two patients had trisomy/tetrasomy chromosome 8
      as the sole abnormality. The other patient with CMMoL had two normal 8
      chromosomes plus one isochromosome 8q; this is the first case of long arm
      chromosome 8 tetrasomy without short arm 8 monosomy. This cytogenetic finding
      suggests the importance of the genes located in the long arms of chromosome 8.

PMID- 10942811
TI  - Analysis of telomeric repeats and telomerase activity in human colon carcinoma
      cells with gene amplification.
AB  - COLO320DM and COLO320HSR are cell lines derived from a human malignant
      neuroendocrine colon carcinoma. Both lines have a 30-40-fold amplification of a
      large DNA domain containing the MYC oncogene. By using fluorescence in situ
      hybridization techniques with a MYC probe, we could demonstrate that MYC
      amplicons are contained in a large marker chromosome in COLO320HSR cells, in
      double minutes (dmin) of COLO320DM cells, and in the interstitial regions of 3-4
      additional chromosomes in both cell lines. Amplicons in homogeneous staining
      regions (HSRs) comprise normal MYC genes, while dmin chromosomes contain PVT/MYC
      chimeras. Although both cell lines showed similar levels of telomerase activity,
      the telomere length and telomere distribution in chromosomal termini were
      considerably lower in COLO320DM than in COLO320HSR cells. This indicates that the
      average telomere length in cancer cells is regulated no only by the rates of
      telomerase activity but also by some other non-enzymatic mechanisms.

PMID- 10942812
TI  - Cells for drug delivery platforms.

PMID- 10942813
TI  - Cellular transplants as sources for therapeutic agents.
AB  - Soluble factors normally produced by cells of the human body are of increasing
      importance as potential therapeutic agents. Although considerable progress has
      been made in understanding the etiology and pathogenesis of disease, in
      developing animal models and newer experimental therapeutics, few discoveries
      have been translated into clinically effective ways of delivering the multiple
      therapeutic agents obtained from living mammalian cells. This review examines the
      use of transplanted cells as alternatives to conventional delivery systems to
      deliver a variety of protein based therapeutic agents. The chapter begins with a
      set of questions to establish the complexity and challenges of this form of drug
      delivery. The following section focuses the discussion on our understanding of
      genetic engineering, tissue engineering, and some areas of developmental biology
      as they relate to the development of this nascent field. Much of the discussion
      has a neuro/endocrine emphasis. The chapter ends by listing the basic ingredients
      needed to push the use of transplanted cells toward medical practice and some
      general comments about future developments.

PMID- 10942815
TI  - Immunocompatibility and biocompatibility of cell delivery systems.
AB  - Immunoisolation therapy overcomes important disadvantages of implanting free
      cells. By mechanically blocking immune attacks, synthetic membranes around
      grafted cells should obviate the need for immunosuppression. The membrane used
      for encapsulation must be biocompatible and immunocompatible to the recipient and
      also to the encapsulated graft. The ability of the host to accept the implanted
      graft depends not only on the material used for encapsulation, but also on the
      defense reaction of the recipient, which is very individual. Such a reaction
      usually starts as absorption of cell-adhesive proteins, immunoglobulins,
      complement components, growth factors and some other proteins on the surface of
      the device. The absorption of proteins is difficult to avoid, but the amount and
      specificity of absorbed proteins can be controlled to some extent by selection
      and modification of the device material. If the adsorption of proteins to the
      surface of the implanted material is reduced, the overgrowth of the device with
      fibroblast-like and macrophage-like cells is also reduced. Cell adhesion at the
      surface of the implanted device is, in addition to the selected polymeric
      material, greatly influenced by the device content. Xenografts trigger a more
      vigorous inflammatory reaction than allografts, most probably due to the release
      of antigenic products from encapsulated deteriorated and dying cells which
      diffuse through the membrane and activate adhering immune cells. There is an
      evident effect of autoimmune status on the fate of the encapsulated graft. While
      encapsulated xenogeneic islets readily reverse streptozotocin-induced diabetes in
      mice, the same xenografts are short-functioning in NOD autoimmune diabetes-prone
      mice. Autoantibodies, to which most devices are impermeable, are not involved.
      Among the cytotoxic factors which are responsible for the limited survival of the
      encapsulated graft the most important are cytokines and perhaps some other low
      molecular-weight factors released by activated macrophages at the surface of the
      encapsulating membrane.

PMID- 10942814
TI  - Technology of mammalian cell encapsulation.
AB  - Entrapment of mammalian cells in physical membranes has been practiced since the
      early 1950s when it was originally introduced as a basic research tool. The
      method has since been developed based on the promise of its therapeutic
      usefulness in tissue transplantation. Encapsulation physically isolates a cell
      mass from an outside environment and aims to maintain normal cellular physiology
      within a desired permeability barrier. Numerous encapsulation techniques have
      been developed over the years. These techniques are generally classified as
      microencapsulation (involving small spherical vehicles and conformally coated
      tissues) and macroencapsulation (involving larger flat-sheet and hollow-fiber
      membranes). This review is intended to summarize techniques of cell encapsulation
      as well as methods for evaluating the performance of encapsulated cells. The
      techniques reviewed include microencapsulation with polyelectrolyte complexation
      emphasizing alginate-polylysine capsules, thermoreversible gelation with agarose
      as a prototype system, interfacial precipitation and interfacial polymerization,
      as well as the technology of flat sheet and hollow fiber-based
      macroencapsulation. Four aspects of encapsulated cells that are critical for the
      success of the technology, namely the capsule permeability, mechanical
      properties, immune protection and biocompatibility, have been singled out and
      methods to evaluate these properties were summarized. Finally, speculations
      regarding future directions of cell encapsulation research and device development
      are included from the authors' perspective.

PMID- 10942816
TI  - Cell delivery to the central nervous system.
AB  - A dysfunctional central nervous system (CNS) resulting from neurological
      disorders and diseases impacts all of humanity. The outcome presents a staggering
      health care issue with a tremendous potential for developing interventive
      therapies. The delivery of therapeutic molecules to the CNS has been hampered by
      the presence of the blood-brain barrier (BBB). To circumvent this barrier,
      putative therapeutic molecules have been delivered to the CNS by such methods as
      pumps/osmotic pumps, osmotic opening of the BBB, sustained polymer release
      systems and cell delivery via site-specific transplantation of cells. This review
      presents an overview of some of the CNS delivery technologies with special
      emphasis on transplantation of cells with and without the use of polymer
      encapsulation technology.

PMID- 10942817
TI  - Cell transplantation for endocrine disorders.
AB  - Current hormonal replacement therapy for endocrine disorders cannot,
      unfortunately, reproduce the complex metabolic interactions of hormones. The
      organ or cell transplantation would be a more physiological approach to the
      treatment of endocrine disorders. For decades, remarkable progress in organ or
      cell transplantation in endocrine disorders has been made, especially in recent
      years. But there are many limitations in the widespread application of
      allotransplantation because of rejection. Various methods of immunomanipulations
      designed to overcome rejection have been proposed, which include
      immunosuppression, immunomodulation and immunoisolation. The transplantation of
      immunoisolated cells and some clinical results of the transplants were reviewed.
      Also a perspective for future directions on endocrine cell transplantation was
      provided in this review. Human islet cell transplantation for the cure of
      diabetes was emphasized in this chapter and other cell transplantation for
      endocrine disorders was also discussed briefly, including parathyroid tissue
      transplantation, bioartificial thyroid transplantation and adrenal cell
      transplantation.

PMID- 10942818
TI  - Gene therapy approaches for modulating bone regeneration.
AB  - Following injury, bone has the ability to regenerate itself to a form and
      function nearly indistinguishable from the pre-injury state. However, if the
      injury is beyond a critical limit, recovery will not occur without therapeutic
      interventions. Autografts and implants with banked bone continue as the
      treatments of choice, although each exhibits limitations and liabilities.
      Alternatives have included the utilization of bone-graft substitutes that may
      incorporate bone derivatives and soluble signaling molecules such as mitogens and
      morphogens. In addition, an evolving treatment modality, gene therapy, offers an
      exciting avenue for bone regeneration. This review presents some of the current
      concepts for developing a rational gene therapy approach in bone regeneration.

PMID- 10942819
TI  - Endothelial cell delivery for cardiovascular therapy.
AB  - Obstructive atherosclerotic vascular disease stands as one of the greatest public
      health threats in the world. While a number of therapies have been developed to
      combat vascular disease, endothelial cell delivery has emerged as a distinct
      therapeutic modality. In this article, we will review the anatomy of the normal
      blood vessel and the biology of the intact endothelium, focusing upon its
      centrality in vascular biology and control over the components of the vascular
      response to injury so as to understand better the motivation for a cell-based
      form of therapy. Our discussion of cell delivery for cardiovascular therapy will
      be divided into surgical and interventional approaches. We will briefly recount
      the development of artificial grafts for surgical vascular bypass before turning
      our attention towards endothelial cell seeded vascular grafts, in which
      endothelial cells effectively provide local delivery of endogenous endothelial
      secretory products to maintain prosthetic integrity after surgical implantation.
      New techniques in tissue and genetic engineering of vascular grafts and whole
      blood vessels will be presented. Methods for percutaneous interventions will be
      examined as well. We will evaluate results of endoluminal endothelial cell
      seeding for treatment of restenosis and gene therapy approaches to enhance
      endogenous re-endothelialization. Finally, we will examine some innovations in
      endothelial cell delivery that may lead to the development of endothelial cell
      implants as a novel therapy for controlling proliferative vascular arteriopathy.

PMID- 10942820
TI  - Validation of volume measurements in esophageal pseudotumors using 3D endoluminal
      ultrasound.
AB  - The purpose of this study was to validate the accuracy and reliability of volume
      measurements using three-dimensional (3D) endoluminal ultrasound (ELUS) in canine
      pseudotumor esophageal specimens in vitro. Pseudotumors were created by injecting
      various volumes of US gel (0.1-1.0 ml) into canine esophageal specimens. A
      stepping-motor was used to pull either a 9, 12.5 or 20 MHz transducer through the
      lumen of the specimen at 1.5 mm/s. Images were downloaded to a LIFE computer
      system for 3D reconstruction. Volume measurements were made by two investigators
      and compared to spiral CT images. Averaging across all measurements, the average
      magnitude of error was 8.7% in individual US determinations and 11. 9% in CT
      measures. Volumes estimated from images spaced 0.5 and 1.0 mm apart, from images
      in the original and reconstructed planes, and from different scan frequencies,
      produced percentage errors that were not statistically significantly different
      from each other on ELUS. 3D ELUS can be used accurately and reproducibly to
      measure tumor volumes with a low mean percent in vitro.

PMID- 10942821
TI  - Fetal ear assessment and prenatal detection of aneuploidy by the quantitative
      three-dimensional ultrasonography.
AB  - The purposes of this study were to use quantitative three-dimensional (3-D)
      ultrasonography to establish the normal charts of three fetal ear-growth indexes,
      (ear length, ear width and ear area), and to validate their efficacy in the
      prenatal diagnosis of fetal trisomies, either separately or as a combination.
      Using quantitative 3-D ultrasonography, we performed a prospective study to
      measure the three fetal ear growth indexes (i.e., ear length, ear width and ear
      area) in 129 singleton pregnancies, including 122 normal fetuses and 7 trisomies.
      The ear shape was also evaluated in these fetuses using both 2-D and 3-D
      ultrasonography. Our results showed that: First, 3-D ultrasonography offers
      better visualization and easier evaluation of fetal ears than 2-D
      ultrasonography. Second, when using the quantitative assessment of 3-D
      ultrasonography, the measurements of ear length, ear width and ear area were all
      correlated significantly with gestational age in normal pregnancies (r = 0.881,
      0.848, and 0.890, respectively). In addition, 3 of 7 fetal trisomies had ear
      length below the tenth percentile, 1 had ear width below the tenth percentile,
      and 2 had ear area below the tenth percentile. Furthermore, with the combination
      of these three measurements, (including ear length, ear width and ear area), the
      sensitivity in detecting fetal trisomies was elevated to 57.1% and the
      specificity was 83.2%. In conclusion, 3-D ultrasonography reduces the limitations
      of 2-D ultrasonography in the evaluation of fetal ears. However, fetal ear
      measurement may not be used as a single ultrasonographic parameter in identifying
      aneuploid fetuses. We recommend using the combination of these three ear growth
      indexes to enhance the detection rate of aneuploidy.

PMID- 10942822
TI  - Intervertebral disc structure: observation by a novel use of ultrasound imaging.
AB  - The internal structure of intervertebral discs is clinically important in the
      management of back pain. No current routine imaging modality is able to image
      disc structure satisfactorily. The aim of this work was to investigate and
      validate ultrasound imaging so that it might be applied to assessment of
      structural integrity and degree of degeneration. The optimum imaging technique
      was determined using a 3.5 MHz probe in one female subject. The applicability of
      this technique to investigate disc structure in the entire thoracolumbar spine
      was further investigated in 13 subjects. The optimum disc imaging technique was
      found to be a posterolateral approach, 1 to 2 cm lateral of the dorsal midline,
      that revealed structure within the disc not apparent using other approaches. It
      was demonstrated that posterolateral imaging introduces a smaller reproducibility
      error in measurements of linear dimensions close to the disc. It is possible to
      observe internal structure within the disc between T11 and L3 in at least 54% of
      individuals.

PMID- 10942823
TI  - Ultrasonic tissue characterization evaluates myocardial viability and ischemia in
      patients with coronary artery disease.
AB  - To evaluate whether or not ultrasonic tissue characterization (UTC) can detect
      jeopardized or salvageable myocardium in patients having chronic coronary artery
      disease, we studied 103 patients with sequential UTC, dobutamine stress
      echocardiography (DSE) and (201)thallium stress-reinjection single-photon
      emission computed tomography (T1-SPECT). This revealed that the weighted
      amplitude of the cyclic modulation of integrated backscatter was larger for the
      myocardium with less ischemia burden or greater viability (p<0.001). The segments
      with larger ischemia burden or the nonviable myocardium demonstrated the contrary
      result. Using the receiver-operating characteristic curve analyses to determine
      the cutoff value of weighted amplitude for various predictions, UTC can detect
      ischemia in normokinetic myocardium (kappa = 0.34 compared to DSE or T1-SPECT)
      and viability in dyssynergic myocardium (kappa = 0.57 compared to DSE and 0.45,
      to T1-SPECT). These observations show that UTC may prove useful in the
      identification and pathophysiological understanding of myocardial ischemia and
      viability.

PMID- 10942824
TI  - Colour Doppler ultrasound in vesicovaginal fistulas.
AB  - The purpose was to evaluate the feasibility of diagnosing vesicovaginal fistulas
      by colour Doppler ultrasound with contrast media. Twelve consecutive patients
      were examined by vaginoscopy, methylene blue test, cystogram and cystoscopy. For
      ultrasound examination, the bladder was filled with saline. Then diluted contrast
      media (Levovist) was instilled. Colour Doppler ultrasound revealed a jet
      phenomenon through the bladder wall toward the vagina, proving the existence of
      the fistula. Eleven patients had vesicovaginal fistulas, one patient a
      vesicoureterovaginal fistula. Colour Doppler ultrasound had correct results in 11
      of 12 patients (92%). In follow-up examinations of four patients during a
      prolonged drainage of the bladder, we could correctly demonstrate the closure of
      one fistula. Colour Doppler ultrasound with contrast media is a new useful
      diagnostic tool in the evaluation and follow-up of vesicovaginal fistulas. It is
      less invasive than cystoscopy and needs no radiation exposure. The examination is
      well tolerated by the patients.

PMID- 10942825
TI  - Systemic assessment of fetal hemodynamics by Doppler ultrasound.
AB  - The aim of our study was to investigate the parameters of fetal circulation of
      normal pregnancies and their relationship to fetal cardiac output. We performed a
      cross-sectional study of 315 normal singleton pregnancies between 20 and 40
      weeks' gestation without fetal chromosomal or structural malformations. After
      follow-up to delivery, 212 patients who fit all the criteria were enrolled for
      final analysis. Blood flow velocity waveforms were obtained from the tricuspid
      and mitral ventricular inflow, ascending aorta (AAO), pulmonary artery (PA),
      middle cerebral artery (MCA), renal artery (RA), umbilical artery (UA),
      descending aorta (DAO), inferior vena cava (IVC) and ductus venosus (DV) using
      duplex (real-time Doppler) ultrasound (US) scanner. The peak velocity of DV, AAO,
      PA and MCA were also obtained. At the intracardiac level, the ratio of peak flow
      velocity of E wave to peak flow velocity of A wave (E:A ratio) of mitral valve
      (MV) increased more rapidly than tricuspid valve (TV) E:A ratio. For the great
      vessels, aortic peak velocity remained higher than the pulmonary peak velocity
      with advancing gestation. The cardiac output closely correlated to the cardiac
      compliance and flow resistance indices at arterial and venous level. The
      acceleration time in the fetal arteries increased with advancing gestation in
      AAO, PA, MCA and DAO, but it decreased in RA and kept constant in UA. In
      addition, the acceleration time of UA was unrelated to cardiac output. The
      changes of the fetal intracardiac, arterial and venous impedances were remarkable
      through the gestation and related to cardiac output. Fetal cardiac output
      correlated well with the changes of arterial resistance, except with the DAO. The
      ventricular compliance increased with advancing gestation, especially in the left
      side, and was highly related to the change of cardiac output. The acceleration
      time in major arteries positively correlated with the gestational age and cardiac
      output, except in UA and RA; this indicates the difference of the changes of mean
      arterial pressure in uteroplacental circulation, fetal organs and great vessels.
      In conclusion, the fetal cardiac output correlated well with the ventricular
      compliance and was influenced by both hemodynamic changes in peripheral
      resistance and mean arterial pressure.

PMID- 10942826
TI  - Feasibility of mitral flow assessment by echo-contrast ultrasound, part I:
      determination of the properties of echo-contrast agents.
AB  - Data on the ultrasonic properties of commercially available contrast agents are
      limited by being instrument-dependent, especially with regard to their
      backscattering properties. The present work describes methods of measurements
      that provide instrument-independent estimations of a contrast agent's attenuation
      coefficient and integrated backscatter index and provide them as functions of its
      concentration. The two studied commercially available contrast agents were
      Albunex and Levovist SHU 508-A, both representative of agents in common use for
      echocardiography. The attenuation coefficients and integrated backscatter indices
      of both agents were found to be a linear function of their concentrations.
      Proportionality coefficients +/- their standard deviations are provided.
      Actually, square root values of the averaged backscatter indices normalized with
      respect to the rms of the reference signal were determined. The coefficients of
      proportionality were found to be: C(A) = 3.11+/-0.1813 dB/mm; C(L) = 0.07+/-0.005
      dB/mm for attenuation coefficients of the Albunex and Levovist contrast agents,
      respectively, and the corresponding values for backscattering were: D(A) = 0.07+/
      0.0054; D(L) = 0.02+/-0.0012. Being apparatus-independent, the findings of the
      study are important prerequisites for the use of these echo-contrast agents as an
      indicator in research for a quantitative assessment of blood flow.

PMID- 10942827
TI  - Feasibility of mitral flow assessment by echo-contrast ultrasound, part II:
      experimental study on a mechanical model of the left heart.
AB  - The feasibility of assessing mitral flow by means of ultrasonic monitoring of
      backscattered power from an echo-contrast agent in the left atrium and left
      ventricle was studied. A mechanical model of the left heart was built in which
      two thin rubber balloons connected to each other in a feedback loop via two
      artificial heart valves mimicked the left atrium and left ventricle. The model
      was driven by compressed air. Its input and output flows were measured as the
      functions of a pacing rate, driving pressure and artificially introduced mitral
      regurgitation. These were compared with the corresponding data derived from the
      ultrasonic measurements that are based on the correlation between echo-contrast
      agent concentration in the volume of interest and the flow through it. Algorithms
      for quantitative estimations of forward stroke volume (cardiac output) and mitral
      regurgitation are given. This study shows, for the first time, both analytically
      and experimentally, that the pulsating modulation of contrast agent concentration
      vs. time curves in the ventricle and atrium volumes is closely related to the
      pulsating nature of the flow in the system. It also shows that the amplitude of
      the atrium concentration modulation is directly proportional to the maximum value
      of the incoming (to atrium) flow.

PMID- 10942828
TI  - An in vitro comparison of ultrasonic contrast agents in solutions with varying
      air levels.
AB  - The performance, in particular, the stability of ultrasound (US) contrast agents
      has yet to be assessed. An in vitro system has been set up to investigate the
      properties of ultrasonic contrast agents under different suspension conditions.
      This is designed to contribute to the optimal use of agents in clinical practice.
      In this study, the contrast agents were introduced into solutions of different
      oxygen concentration levels, as might be encountered in blood, and their relative
      performance was assessed in terms of decay in the solution environment. The
      partial pressures of oxygen in those solutions ranged between 1.5 and 26 kPa.
      Three IV and one arterial contrast agents were used: Levovist, DMP115, Quantison
      and Myomap. Levovist showed the highest sensitivity to oxygen concentration in
      the solution, and the other three proved tolerant for the above values of oxygen
      concentrations.

PMID- 10942829
TI  - Study of ultrasonic contrast agents using a dual-frequency band technique.
AB  - We have developed a dual-frequency band technique to study frequency-dependent
      phenomena associated with ultrasonic contrast agents. Our technique uses a
      superimposed high-frequency (10 MHz) broad-band ultrasound (US) pulse to
      investigate contrast agent interaction with a low-frequency (e.g., 0.5 MHz)
      ultrasonic field. Our digitally controlled system has the ability to produce two
      colinear, confocal US pulses at different center frequencies, to adjust the
      relative phasing and pulse repetition frequency of each pulse, and to acquire
      digital backscatter data. A series of experimental studies demonstrated that the
      high-frequency backscatter signal responded to several phenomena induced in
      contrast agent particles by the low-frequency beam. These phenomena included
      radial pulsations, nonlinear oscillations and depletion. Initial results also
      demonstrated a relative phase shift between the high- and low-frequency signals;
      this shift is due to a difference in sound velocity at these frequencies, and it
      may convey information about the contrast agent concentration.

PMID- 10942830
TI  - Ultrasound shear wave imaging for bone.
AB  - Recently, a computer-controlled scanning ultrasound (US) imaging system was
      developed in our laboratory. It includes a pair of broadband 48-MHz focusing
      copolymer transducers. The apertures of the transducers and their f-numbers were
      identically equal to 2 mm and 2.25, respectively. A specimen can be moved in a 10
      microm increment in its plane and its normal direction can be rotated along the
      US propagation direction. It can be used to produce transmission-mode images of
      shear waves, as well as longitudinal waves for solid specimens. Shear waves in
      solids were generated by mode conversion. The results of the longitudinal and
      shear-wave US images for a piece of compact bovine bone obtained using this
      system are presented. Shear-wave images combined with longitudinal images can
      provide a more complete mechanical characterization of bone.

PMID- 10942831
TI  - Nonlinear stress-strain relationships in tissue and their effect on the contrast
      to-noise ratio in elastograms.
AB  - The practice of elastography is generally limited to small applied compressions
      (typically 1%), under the assumption of a linear stress-strain relationship in
      biological tissue. However, the recent reports of larger applied compressions and
      precompression levels to increase the strain contrast violate the above
      assumption. The nonlinear stress-strain relationships in different breast tissue
      types significantly alter the contrast in elastography, especially for large
      applied compression. The moduli of normal fibrous and glandular breast tissue
      (along with cancerous lesions) are strain-dependent, with tissue stiffness
      increasing with applied compression. In this paper, we illustrate that the strain
      dependence of the modulus has a significant impact on the elastographic contrast
      and on the contrast-to-noise ratio, and may even cause a reversal of the contrast
      in certain situations. This paper also emphasizes the effect of the
      precompression strain level on the strain contrast.

PMID- 10942832
TI  - Intrinsic spectral broadening (ISB) in ultrasound Doppler as a combination of
      transit time and local geometrical broadening.
AB  - Doppler signals collected with a focused transducer are known to be affected by
      the so-called intrinsic spectral broadening (ISB). This article aims to point out
      how ISB is, in general, related to both the limited lateral extent of a focused
      beam (leading to a finite transit time), and the presence of several local
      insonation angles around the beam axis, due to focusing and diffraction effects
      (local geometrical broadening). The influence of these two elementary spectral
      contributions on the whole ISB is shown by considering the Doppler signal as
      simultaneously modulated in amplitude and frequency, and applying well-known
      relationships employed in the communication field. Such an analysis reveals that
      transit time and local geometrical broadening are two different phenomena, whose
      simultaneous knowledge is necessary for correctly evaluating the overall ISB.
      Finally, thanks to a novel technique for separately measuring transit time and
      local geometrical broadening effects on transducers with markedly different
      focusing properties, more than 1000 experimental acquisitions show how a proper
      combination of such measured contributions gives an accurate ISB estimation,
      confirming the theoretical expectations.

PMID- 10942833
TI  - A fast rotating scanning unit for real-time three-dimensional echo data
      acquisition.
AB  - Most three-dimensional (3-D) echocardiography (3-DE) systems today are based on
      off-line methods where a large number of cross-sectional 2-D scans have to be
      acquired sequentially before a 3-D image can be reconstructed. Because
      acquisition is done step-by-step based on ECG triggering plus respiratory gating,
      this introduces motion artefacts and takes significant acquisition time. Another
      3-D approach is based on 2-D transducers and parallel beam-forming. Such a system
      is very complex. In this manuscript, a fast continuously-rotating scanning unit,
      based on a 64-element phased-array transducer, is described. Typical rotation
      speed of the 3-D unit is 8 rotations per s. Therefore, 16 3-D volume datasets can
      be acquired per s in real-time. The first clinical examples as acquired with this
      probe are presented.

PMID- 10942834
TI  - MRI detection of the thermal effects of focused ultrasound on the brain.
AB  - This study tested the hypothesis that MRI thermometry can be correlated with the
      different degrees of tissue damage observed after focused ultrasound (US)
      exposure of brain. The brains of 6 rabbits were sonicated to calibrate the MRI
      proton resonant shift with temperature. In addition, 13 rabbits were sonicated at
      acoustic powers ranging from 3.5 to 17.5 W. The experiments were performed in a
      1.5-T MRI scanner with the temperature-sensitive phase imaging used during the
      sonications of 4-5 different locations in each rabbit. MR images were obtained 2
      h and 2 days after the sonications, depending on when the animals were
      sacrificed. Whole brain histologic evaluation was performed by sectioning the
      brain and performing a microscopic investigation. The MRI-derived temperature
      elevation was found to correlate well with the degree of tissue damage. In
      addition to the common histology findings, apoptotic cells were observed in the
      lesions. The T1-weighted contrast enhanced and T2-weighted scans both detected
      the brain damage. The applied acoustic power did not correlate well with the
      degree of damage. As a conclusion, the results showed that the measurement of
      temperature elevations by MRI during sonications can improve the accuracy and
      safety of clinical US brain surgery.

PMID- 10942835
TI  - Plasma preparation from whole blood using ultrasound.
AB  - A technique to efficiently separate plasma from human whole blood is described.
      Essentially, 3-mL samples are held on the axis of a tubular transducer and
      exposed for 5.7 min to an ultrasonic standing wave. The cells concentrate into
      clumps at radial separations of half wavelength. The clumps grow in size and
      sediment under gravity. A distinct plasma/cell interface forms as the cells
      sediment. The volume of clarified plasma increases with time. The separation
      efficiencies of transducers of 29-mm and 23-mm internal diameters driven, by test
      equipment, at radial resonances of 3.4 and 1.5 MHz, respectively, were compared.
      The average efficiency of separation was 99.6% at 1.5 MHz and 99.4% with the 3.4
      MHz system. The cleared plasma constituted 30% of the sample volume at 1.5 MHz
      and 25% at 3. 4 MHz. There was no measurable release of haemoglobin or potassium
      into the suspending phase, indicating that there was no mechanical damage to
      cells at either frequency. A total of 114 samples from volunteers and patients
      were subsequently clarified in a 1.5-MHz system driven by an integrated
      generator. The average efficiency of clarification of blood was 99.76% for the
      latter samples. The clarification achieved is a significant improvement on that
      previously reported (98.5%) for whole blood exposed to a planar ultrasonic
      standing wave field (Peterson et al. 1986). We have, therefore, now achieved a
      six-fold reduction of cells in plasma compared to previous results.

PMID- 10942836
TI  - Acceleration of thrombolysis with ultrasound through the cranium in a flow model.
AB  - Thrombolysis is an efficient therapy for hyperacute stroke within a limited time
      window. Neurological outcome depends on the recanalization time of the occluded
      vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic
      fibrinolysis in vitro. We examined the effects of transcranially applied US on
      recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow
      model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model
      and treated with rt-PA during 1-MHz US exposure (0.5 W/cm(2); spatial peak,
      temporal peak intensity). Transcranial and direct US application in combination
      with rt-PA significantly (p<0.001) shortened recanalization time, increased
      perfusion flow and reperfusion rate in comparison with rt-PA-mediated
      thrombolysis alone. Recanalization rate within 30 min was 90-100% in the US
      exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest
      that transcranial application of 1-MHz US may accelerate reperfusion and
      recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated
      thrombolysis. Shortening of recanalization time could contribute to optimizing
      effects of acute thrombolytic stroke therapy.

PMID- 10942846
TI  - New Initiative. Neuropsychopharmacology Online Rapid Publication.

PMID- 10942837
TI  - Ultrasound enhancement of liposome-mediated cell transfection is caused by
      cavitation effects.
AB  - Cationic liposomes (CL) are widely used vectors for gene transfer. Recently,
      ultrasound (US) was reported to enhance liposome-mediated gene transfer to
      eucaryotic cells in culture. The present study was aimed at studying the effects
      of 2-MHz pulsed Doppler US on malignant brain tumor cells transfection by
      cationic liposome/plasmid-DNA complexes (lipoplexes). Cationic liposomes
      consisting of DOSPA/DOPE were complexed with a plasmid carrying the cDNA encoding
      green autofluorescent protein (EGFP). Rodent (9L) and canine (J3T) glioma cells
      were exposed to pulsed US in the presence of EGFP-lipoplexes. A diagnostic
      transcranial Doppler device (MultiDop L) was used for insonation for 30, 60, and
      90 s at 2 MHz/0.5 W/cm(2). To eliminate US reflection and cavitation, a custom
      made absorption chamber was designed, where US is applied through a water tank
      before interacting with the cells and is fully absorbed after passing through the
      cell layer. Expression of the marker gene EGFP was quantified by FACS analysis
      and intravital fluorescent microscopy. Cell viability was accessed by Trypan Blue
      staining. US treatment of tumor cells on microplates for 60 s yielded a
      significant increase in transfection rates without damaging the cells, but 90-s
      treatment killed most of the cells. In the absorption chamber, no significant
      effects of US on transfection were noted. Additional experiments employed US
      contrast agent (Levovist, Schering) which was able to significantly increase
      tumor cell transfection rate by enhancing cavitation effects, and also severely
      damaged most cells when applied at a concentration of 200 mg/mL. In conclusion,
      our results support the assumption that US effects on lipoplex transfection rates
      in brain tumor cells in culture are mediated by cavitation effects.

PMID- 10942847
TI  - To model a psychiatric disorder in animals: schizophrenia as a reality test.
AB  - Animal modeling has been instrumental in dissecting pathophysiological mechanisms
      and designing more effective therapies in many areas of medicine but not so in
      psychiatry. The critical obstacle in modeling psychiatric disorders has been
      limited information about their origin and underlying neural mechanisms.
      Recently, with rapidly growing knowledge about the neurobiology and genetics of
      psychiatric disorders, animal models of these diseases are gaining popularity in
      psychiatric research. New models of schizophrenia mimic biological phenomena
      associated with the clinical condition, particularly developmental changes in the
      cortex, abnormalities of glutamate neurotransmission, and genetic characteristics
      of selected behavioral traits. The biological fidelity of some aspects of these
      new models suggests that they will be useful in the development of new therapies,
      in identifying candidate genes, and in providing new insights about
      pathophysiology and etiology.

PMID- 10942848
TI  - The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood
      flow in dorsolateral prefrontal cortex of monkeys performing a spatial working
      memory task.
AB  - Research indicates that norepinephrine enhances the working memory functions of
      the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A
      adrenoceptors. The current study examined the effects of the alpha-2A
      adrenoreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPECT
      measures of regional cerebral blood flow (rCBF) in monkeys performing a spatial
      working memory task. Animals were infused with the SPECT blood flow tracer, Tcm
      99m ECD, through an indwelling intravenous catheter while performing the working
      memory task. Guanfacine treatment significantly improved cognitive performance of
      the working memory task, and significantly increased rCBF values in the
      dorsolateral PFC, the brain region most tightly associated with performance of
      spatial working memory tasks. In contrast, guanfacine had no significant effect
      on rCBF in the superior temporal cortex, an auditory association area unrelated
      to task performance. These data are consistent with the hypothesis that alpha-2A
      adrenoceptor stimulation preferentially enhances functioning of the PFC.

PMID- 10942849
TI  - Synergistic effects of olanzapine and other antipsychotic agents in combination
      with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex.
AB  - To understand the mechanism of the clinical efficacy of olanzapine and fluoxetine
      combination therapy for treatment-resistant depression (TRD), we studied the
      effects of olanzapine and other antipsychotics in combination with the selective
      serotonin uptake inhibitors fluoxetine or sertraline on neurotransmitter release
      in rat prefrontal cortex (PFC) using microdialysis. The combination of olanzapine
      and fluoxetine produced robust, sustained increases of extracellular levels of
      dopamine ([DA](ex)) and norepinephrine ([NE](ex)) up to 361 +/- 28% and 272 +/-
      16% of the baseline, respectively, which were significantly greater than either
      drug alone. This combination produced a slightly smaller increase of serotonin
      ([5-HT](ex)) than fluoxetine alone. The combination of clozapine or risperidone
      with fluoxetine produced less robust and persistent increases of [DA](ex) and
      [NE](ex). The combination of haloperidol or MDL 100907 with fluoxetine did not
      increase the monoamines more than fluoxetine alone. Olanzapine plus sertraline
      combination increased only [DA](ex). Therefore, the large, sustained increase of
      [DA](ex), [NE](ex), and [5-HT](ex) in PFC after olanzapine-fluoxetine treatment
      was unique and may contribute to the profound antidepressive effect of the
      olanzapine and fluoxetine therapy in TRD.

PMID- 10942850
TI  - The effects of an alpha-2 adrenergic agonist, guanfacine, on rCBF in human cortex
      in normal controls and subjects with focal epilepsy.
AB  - Alpha-2 noradrenergic agonists may have wide applicability in the treatment of
      pre-frontal cortex deficits in primates and behavioral dysfunction in man. We
      have undertaken this study to determine the effect of an alpha-2 agonist,
      guanfacine, on regional cerebral blood flow (rCBF) in humans. Three subject
      groups were evaluated: normal controls, subjects with frontal lobe epilepsy
      (FLE), and subjects with temporal lobe epilepsy (TLE). All underwent a number of
      PET scans using 15O-water, with half before and half after a single dose of
      guanfacine. A wide area of increased rCBF was seen in the frontal lobe, maximal
      at the central region, following guanfacine in controls and subjects with TLE.
      Smaller areas of decrease in rCBF were seen in the posterior temporal-occipital
      cortex. In the FLE group a decrease in rCBF was seen in the dorsal prefrontal
      cortex on the epileptogenic side with only small increases seen in the mid- to
      anterior temporal perisylvian areas. The ability of alpha-2 agonists to enhance
      performance of tasks reliant on prefrontal cortex, without improving tasks
      believed to rely on intact temporal-hippocampal function, may be explained by
      these results. Epileptogenic zones appear to create both direct and indirect
      changes in patterns of drug response. Further studies on the cognitive properties
      of these agents in humans should be encouraged.

PMID- 10942851
TI  - Neurosteroids ameliorate conditioned fear stress: an association with sigma
      receptors.
AB  - Mice exhibited a marked suppression of motility (conditioned fear stress) when
      placed in an environment in which they had previously received an electric
      footshock. This conditioned fear stress response was dose-dependently attenuated
      by neurosteroids such as dehydroepiandrosterone sulfate (DHEAS; 25 and 50 mg/kg,
      s.c.) and pregnenolone sulfate (PREGS; 10-50 mg/kg, s.c.), and by a putative
      sigma(1) receptor agonist, (+)-N-allylnormetazocine ((+)-SKF-10,047; 3 and 6
      mg/kg, s.c.). However, progesterone (PROG; 10-50 mg/kg, s.c. ) and
      allopregnanolone (5 and 20 mg/kg, s.c.) had no effect on this stress response.
      The attenuating effects of DHEAS (50 mg/kg, s.c.), PREGS (50 mg/kg, s.c.), and
      (+)-SKF-10,047 (6 mg/kg, s.c.) were reversed by NE-100 (5 mg/kg, i.p.), a
      sigma(1) receptor antagonist and PROG (5 or 10 mg/kg, i.p.). When DHEAS (25
      mg/kg) was co-administered with (+)-SKF-10,047 (3 mg/kg) at doses that do not
      affect the conditioned fear stress response by themselves, motor suppression was
      significantly attenuated. In mice showing the conditioned fear stress response,
      the serum concentration of DHEAS was lower than that in non-shocked mice. These
      results suggest that the attenuating effects of DHEAS and PREGS on the
      conditioned fear stress response are mediated via sigma(1) receptors and that
      PROG has a sigma(1) receptor antagonistic property. Further, the endogenous DHEAS
      may be involved in the expression of conditioned fear stress response in mice.

PMID- 10942852
TI  - beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro:
      implications for antidepressant therapy.
AB  - A novel strategy for improving the treatment of depressive illness is
      augmentation of antidepressants with a 5-HT1(1A) autoreceptor antagonist.
      However, trials using the 5-HT1(1A)/beta-blocker pindolol are proving
      inconsistent. We report how positron emission tomography (PET) and in vitro
      autoradiography can inform trials of antidepressant augmentation. We show that in
      healthy volunteers, in vivo, pindolol (n = 10) and penbutolol (n = 4), but not
      tertatolol (n = 4) occupy the human 5-HT(1A) receptors, at clinical doses.
      Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high
      affinity for human 5-HT(1A) receptors in post-mortem brain slices (n = 4).
      Pindolol shows preference for 5-HT(1A) autoreceptors versus the post-synaptic
      receptors both in vitro and in vivo. Our data reveal that pindolol doses used in
      antidepressant trials so far are suboptimal for significant occupancy at the 5
      HT(1A) autoreceptor. Penbutolol or higher doses of pindolol are candidates for
      testing as antidepressant augmenting regimes in future clinical trials.

PMID- 10942854
TI  - Expression of fos-related antigens in the nucleus accumbens during opiate
      withdrawal and their attenuation by a D2 dopamine receptor agonist.
AB  - Previous studies from this laboratory indicated that D2 dopamine (DA) receptors
      within the nucleus accumbens (NAc) are important for regulating somatic signs of
      opiate withdrawal. The present study measured the expression of Fos-related
      antigens (FRAs) within the NAc during opiate withdrawal to determine whether
      decreases in somatic withdrawal signs produced by a D2 receptor agonist are
      accompanied by related changes in accumbens neuronal activity. In an initial
      experiment, quantitative analyses of FRA immunoreactivity revealed increases in
      the number of FRA-positive cells throughout the NAc of opiate dependent animals
      undergoing naltrexone-precipitated withdrawal relative to dependent or non
      dependent animals that did not experience withdrawal. A second experiment showed
      that somatic signs and FRA expression within the NAc could each be attenuated
      when the D2 agonist propylnorapomorphine (NPA; 0.1 or 0.3 mg/kg, i.p.) was
      administered prior to naltrexone-precipitated withdrawal. These findings suggest
      that D2 regulation of neuronal activity within the NAc may be important for the
      expression of opiate withdrawal symptoms.

PMID- 10942853
TI  - Potentiation by (-)Pindolol of the activation of postsynaptic 5-HT(1A) receptors
      induced by venlafaxine.
AB  - The increase of extracellular 5-HT in brain terminal regions produced by the
      acute administration of 5-HT reuptake inhibitors (SSRI's) is hampered by the
      activation of somatodendritic 5-HT(1A) autoreceptors in the raphe nuclei. The
      present in vivo electrophysiological studies were undertaken, in the rat, to
      assess the effects of the coadministration of venlafaxine, a dual 5-HT/NE
      reuptake inhibitor, and (-)pindolol on pre- and postsynaptic 5-HT(1A) receptor
      function. The acute administration of venlafaxine and of the SSRI paroxetine (5
      mg/kg, i.v.) induced a suppression of the firing activity of dorsal hippocampus
      CA(3) pyramidal neurons. This effect of venlafaxine was markedly potentiated by a
      pretreatment with (-)pindolol (15 mg/kg, i.p.) but not by the selective beta
      adrenoceptor antagonist metoprolol (15 mg/kg, i.p.). That this effect of
      venlafaxine was mediated by an activation of postsynaptic 5-HT(1A) receptors was
      suggested by its complete reversal by the 5-HT(1A) antagonist WAY 100635 (100
      microg/kg, i.v.). A short-term treatment with VLX (20 mg/kg/day x 2 days)
      resulted in a ca. 90% suppression of the firing activity of 5-HT neurons in the
      dorsal raphe nucleus. This was prevented by the coadministration of (-)pindolol
      (15 mg/kg/day x 2 days). Taken together, these results indicate that (-)pindolol
      potentiated the activation of postsynaptic 5-HT(1A) receptors resulting from 5-HT
      reuptake inhibition probably by blocking the somatodendritic 5-HT(1A)
      autoreceptor, but not its postsynaptic congener. These results support and extend
      previous findings providing a biological substratum for the efficacy of pindolol
      as an accelerating strategy in major depression.

PMID- 10942855
TI  - N-[1-(2-benzo[b]thiophenyl)Cyclohexyl]- piperidine (BTCP) exerts cocaine-like
      actions on drug-maintained responding in rats.
AB  - The effects of N-[1-(2-benzo[b]thiophenyl)cyclohexyl]- piperidine (BTCP), a
      phencyclidine derivative that acts as a potent dopamine reuptake inhibitor, were
      examined on cocaine self-administration in rats. The effects of BTCP (0, 4, 8,
      16, and 32 mg/kg, i.p.) on cocaine self-administration were tested against
      cocaine doses on both the ascending (0.0625 mg/infusion) and descending (0.25
      mg/infusion) limb of the dose-response function. BTCP decreased self
      administration of the 0.25-mg cocaine dose in a dose-dependent manner. A 16-mg/kg
      dose of BTCP that strongly suppressed self-administration of the 0.25-mg cocaine
      dose increased the intake at the 0.0625-mg dose of cocaine. Moreover, cocaine and
      BTCP pretreatments produced similar patterns of decreases in self-administration
      of cocaine on the descending limb of the dose-response function. The results
      suggest that BTCP has cocaine-like actions and produces a leftward shift of the
      dose-response curve for cocaine self-administration, indicating that the
      phencyclidine analog may substitute under certain conditions for the reinforcing
      effects of cocaine in self-administering rats.

PMID- 10942856
TI  - Buprenorphine-induced changes in mu-opioid receptor availability in male heroin
      dependent volunteers: a preliminary study.
AB  - A principle of opioid pharmacotherapy is that high medication doses should occupy
      fractionally more opioid receptors that mediate heroin effects. In this
      preliminary study we examined in vivo mu opioid receptor (muOR) binding in three
      healthy opioid-dependent volunteers during maintenance on 2 and 16 mg sublingual
      buprenorphine (BUP) liquid, and after detoxification (0 mg) under double-blind,
      placebo-controlled conditions, and once in matched controls. Binding measures
      were obtained with the muOR-selective radioligand [11C]carfentanil (CFN) and PET
      4 hrs after BUP administration. BUP induced dose-dependent reductions in muOR
      availability, 36-50% at 2 mg and 79-95% at 16 mg relative to placebo. Heroin
      abusers also had greater muOR binding potential in the inferofrontal cortex and
      anterior cingulate regions during placebo, compared to matched controls. Further
      studies are warranted to examine the relationship of muOR availability with BUP
      therapeutic actions, and the clinical implications of increased muOR binding
      during withdrawal.

PMID- 10942857
TI  - Context-specific enhancement of glutamate transmission by cocaine.
AB  - The repeated injection of cocaine causes an increase in the capacity of a
      subsequent acute injection to elevate extracellular glutamate levels in the
      nucleus accumbens, and the present study sought to determine if the elevation in
      extracellular glutamate is regulated by the pairing of environmental stimuli with
      drug administration. Three treatment groups were injected daily for seven days
      with saline or cocaine (15 mg/kg, ip); 1) injection of saline in the home cage,
      2) injection of cocaine in the home cage (cocaine-unpaired), and 3) injection of
      cocaine in the test apparatus (cocaine-paired). Three weeks following the last
      daily injection dialysis probes were placed into the nucleus accumbens and all
      rats were injected with saline followed by cocaine. Basal levels of extracellular
      glutamate were significantly reduced in the cocaine-paired treatment group.
      Moreover, only in the cocaine-paired group did the cocaine injection elevate
      extracellular glutamate. Repeated administration of cocaine also produces an
      enduring increase in the motor stimulant response to an acute cocaine injection
      and it was previously found that administration of the alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid and kainic acid glutamate receptor antagonist 6
      cyano-7-nitroquinoxaline-2, 3-dione inhibited the sensitized, but not the acute
      motor, response to cocaine. In this study it was found that the motor stimulant
      response elicited by cocaine was blunted by pretreatment of the nucleus accumbens
      with 6-cyano-7-nitroquinoxaline-2,3-dione only in animals receiving daily cocaine
      injections in the paired environment. In contrast, the N-methyl-D-aspartate
      glutamate receptor antagonist R-(-)-3-(2-carboxypiperazin-4-yl)-propyl-1
      phosphonic acid did not significantly affect cocaine-induced motor activity in
      any treatment group. These data support a hypothesis that environmental stimuli
      previously associated with daily cocaine administration can modulate glutamate
      transmission in the nucleus accumbens in a manner affecting cocaine-induced
      behavior.

PMID- 10942858
TI  - Do physicians judge a study by its cover? An investigation of journal attribution
      bias.
AB  - The effect of a journal's prestige on readers' impressions of an article is
      unknown. Two hypotheses were tested: first, that attribution of a study to a
      "high" prestige journal would be associated with improved impressions and
      attribution to a "low" prestige journal would be associated with diminished
      impressions; and second, that formal training in epidemiology and biostatistics
      would mitigate the effects of this journal attribution bias. The study was
      designed as a trial among a random sample of 264 internists. Participants were
      asked to read an article and an abstract from either the Southern Medical Journal
      (SMJ) or the New England Journal of Medicine (NEJM). Questionnaires were
      constructed that either attributed the article or abstract to its source or
      presented it as unattributed. After each article or abstract, respondents were
      asked to rate the quality of the study, the appropriateness of the methodology
      employed, the significance of the findings, and its likely effects on their
      practice. A 20-point impression score was created based on responses to these
      statements. The effect of attribution to a specific journal and formal
      epidemiology training on impression scores were assessed using linear regression.
      Of the 399 eligible participants, 264 questionnaires were returned (response rate
      66%). Differences in impression scores associated with attribution of an article
      or abstract to the NEJM were.71 [95% C.I. (-.44-1.87)] and.50 [95% C.I. (-.87
      1.87)] respectively; differences in impression scores associated with attribution
      of an article or abstract to the SMJ were -.12 [95% C.I. (-1.53-1.30)] and -.95
      [95% C.I. (-2.41-.52)]. A stratified analysis demonstrated that epidemiology
      training did not meaningfully alter the effect of journal attribution on
      participants' impression scores. If journal attribution bias exists, it is likely
      to exert small and clinically insignificant effects when physicians read articles
      carefully. Formal training in epidemiology and biostatistics does not appear to
      alter these results.

PMID- 10942859
TI  - Functional status and perceived quality of life in adults with and without
      chronic conditions.
AB  - The objective of this study was to evaluate the association between self-reported
      functional status and quality of life in adults with and without chronic
      conditions. Data were obtained on functional status (Sickness Impact Profile,
      SIP), and perceived quality of life (Perceived Quality of Life Scale, PQoL) from
      454 persons in nine groups with widely varying levels of functional status and
      disability. Multiple regression was used to analyze the association controlling
      for demographic characteristics (age, gender, educational level, income, marital
      status), self-rated health status, and depressive symptoms. PQoL was lowest for
      persons using wheelchairs and highest for older well adults. Scores decreased as
      SIP scores increased. Overall, being older, reporting better functional status,
      and having fewer depressive symptoms were significantly associated with higher
      quality of life (adjusted R(2) = 0.60). This pattern held for most subgroups,
      although the association was much lower for adults with AIDS and younger well
      adults where ceiling effects were observed in functional status. Functional
      status and perceived quality of life are highly associated but are distinct in
      many populations. Depressive symptoms and self-rated health are important
      mediators of the relationship to include in future studies. Amelioration of
      depressive symptoms through environmental modification and individual treatment
      are potential strategies for improving on this association in adults with chronic
      conditions.

PMID- 10942860
TI  - Do medical devices have enhanced placebo effects?
AB  - Although the placebo in a clinical trial is often considered simply a baseline
      against which to evaluate the efficacy of a clinical intervention, there is
      evidence that the magnitude of placebo effect may be a critical factor in
      determining the results of a trial. This article examines the question of whether
      devices have enhanced placebo effects and, if so, what the implications may be.
      While the evidence of an enhanced placebo effect remains rudimentary, it is
      provocative and therefore worthy of further study. Suggestions are made,
      therefore, for how such an effect can be investigated without violating the
      principles of informed consent.

PMID- 10942861
TI  - Canadian Acute Respiratory Illness and Flu Scale (CARIFS): development of a valid
      measure for childhood respiratory infections.
AB  - Although acute respiratory infection (ARI) is the most frequent clinical syndrome
      in childhood, there is no validated measure of its severity. Therefore a parental
      questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale
      (CARIFS). A process of item generation, item reduction, and scale construction
      resulted in a scale composed of 18 items covering three domains; symptoms (e.g.,
      cough); function (e.g., play), and parental impact (e.g., clinginess). The
      validity of the scale was evaluated in a study of 220 children with ARI.
      Construct validity was assessed by comparing the CARIFS score with physician,
      nurse, and parental assessment of the child's health. Data were available from
      206 children (94%). The CARIFS correlated well with measures of the construct
      (Spearman's correlations between 0.36 and 0.52). Responsiveness was shown, with
      90% of children having a CARIFS score less than a quarter of its initial value,
      by the tenth day.

PMID- 10942862
TI  - Predictive validity of symptoms and signs in the neck and shoulders.
AB  - A standardized examination protocol was developed for the assessment of neck and
      shoulder disorders in primary health care. We investigated to what extent the
      symptoms and signs can predict sick leave due to neck and shoulder disorders. Our
      study involved 474 patients seeking medical advice from an occupational health
      service. Most of the 20 symptoms and 15 signs of the protocol were associated
      with the number of sick leave days within the 60-day postexamination period, but
      only three symptoms (short duration, high pain intensity, and continuous pain)
      and two signs (pain in the upper limb during rotation of head and pain in the
      shoulder during abduction of arm) retained their significance in a multivariate
      model. No unambiguous subset of protocol items can be suggested for general use.
      The predictive validity should be tested in other populations and settings before
      a conclusion is drawn about the external validity of the results.

PMID- 10942863
TI  - Iron stores and coronary artery disease: a clinical application of a method to
      incorporate measurement error of the exposure in a logistic regression model.
AB  - Rates of coronary artery disease (CAD) increase sharply after menopause. We
      examined the hypotheses that high iron stores, as measured by plasma ferritin
      levels, are a risk factor for CAD and that the increase in iron stores after
      menopause is at least in part responsible for the rise in CAD in women. We also
      investigated measurement error of plasma ferritin using a Bayesian conditional
      independence model and incorporated it into the estimation of the odds ratio (OR)
      for males. Cases had >/=1 coronary artery stenosis >/=70%. Controls had no
      visible coronary lesions on angiography. The median plasma ferritin level was 48
      mg/L (interquartile range: 28 to 86) among 244 cases and 45 mg/l (24 to 85) among
      140 controls. The multivariate analyses among females, males, and females and
      males combined did not support an association between plasma ferritin levels and
      CAD (OR for one unit change in log ferritin 1.01, 95% CI 0.71-1.44, OR 0.95, 95%
      CI 0.66-1.37 and OR 0.95, 95% CI 0.75-1.21, respectively). Accounting for the
      measurement error of ferritin in males slightly improved the precision of the
      estimate of the OR but did not unmask an association (OR: 0.94, 95% CI 0.69
      1.30). We conclude that high ferritin levels before or after menopause are not
      associated with CAD. Measurement error might be considered in situations where a
      one-time measurement is assumed to be representative of long-term exposure.

PMID- 10942864
TI  - Competing risk adjustment reduces overestimation of opportunistic infection rates
      in AIDS.
AB  - To illustrate the importance of adjusting the estimates of cumulative incidence
      of acquired immunodeficiency syndrome (AIDS) related illnesses for competing risk
      of other causes of death, we compared unadjusted and adjusted (for competing
      events) incidence estimates for four AIDS illnesses: pneumocystis cavinii
      pneumonia (PCP), mycobacterium avium complex (MAC), cytomegalovirus (CMV), and
      esophageal candidiases. The study population was patients followed by the Johns
      Hopkins Hospital AIDS Service between 1989 to 1995. Ratios of 4 year unadjusted
      incidence estimates to 4 year adjusted incidence estimates for the four diseases
      ranged from 1.38 to 1.86, corresponding to cumulative death rates of 61% to 69%.
      For CMV, the ratios of 4 year unadjusted to adjusted incidence estimates for five
      groups of patients ranged from 1.5 to 2.33, corresponding to cumulative death
      rates of 48% to 78%. We conclude that ignoring the competing risk of death can
      result in substantial overestimation of disease occurrence, which may give
      misleading results in estimating and comparing the occurrence of a disease of
      interest.

PMID- 10942865
TI  - Assessing the Saskatchewan database for outcomes research studies of depression
      and its treatment.
AB  - This study was conducted to evaluate the validity of using the Saskatchewan
      Health administrative claims databases for conducting depression research. To
      develop a claims-based definition of depression, we identified a cohort of
      individuals who began a "new" period of antidepressant use (no use 180 days
      prior) from which we selected a stratified random sample (n = 600) for medical
      record abstraction. The medical record diagnosis was used as the gold standard
      for judging our database definitions of depression. After defining a primary
      database definition of depression, we tried to refine it using medically probable
      scenarios and assessed refinement by agreement statistics. Defining depression
      with ICD9 codes 296 (affective disorders), 309 (adjustment reaction), and 311
      (depressive disorders), the sensitivity (Se), specificity (Sp), positive (PV+)
      and negative predictive (PV-) values were: 71%, 85%, 86%, and 70%, respectively.
      Algorithms that limited the number of false-negatives resulted in: Se = 84% and
      PV- = 77% whereas those that limited false-positives resulted in: Sp = 90% and
      PV+ = 86%. Although our depression definition requires treatment with
      antidepressants, this definition will allow us to conduct future studies of
      depression and its treatment using the Saskatchewan Health databases.

PMID- 10942866
TI  - Risk of myocardial infarction after oophorectomy and hysterectomy.
AB  - To determine the risk of developing a first myocardial infarction after a
      hysterectomy and/or oophorectomy. Case-cohort analysis performed among 17,126
      women in the Uppsala Health Care Region of Sweden, who had undergone a
      hysterectomy and/or oophorectomy in 1965 to 1983. Record linkage was used for
      follow-up and medical records to ascertain the actual history of oophorectomy.
      Risk estimates were calculated by relating the observed number of cases in the
      cohort to that expected on the basis of incidence rates in the population.
      Overall, 214 cases of myocardial infarction were observed. In premenopausal women
      a bilateral oophorectomy alone tended to increase the relative risk 1.6; 95% CI
      0.8-3.1, but this operation combined with hysterectomy increased the risk only
      among those aged 50 and over at surgery. Hysterectomy at premenopausal age or
      unilateral oophorectomy did not alter the risk of myocardial infarction. In
      naturally menopausal women, hysterectomy-mainly for uterine myoma-was associated
      with a four-fold increase in relative risk (3.8; 95% CI 1.9-7.8). Hysterectomy
      for treatment of myoma performed after a natural menopause is linked to an excess
      risk for myocardial infarction. Bilateral oophorectomy before menopause may
      increase the risk of myocardial infarction.

PMID- 10942867
TI  - Chin-Shan Community Cardiovascular Cohort in Taiwan-baseline data and five-year
      follow-up morbidity and mortality.
AB  - A cohort consisting of 3602 residents (82.8% of the target population) aged 35
      years and older was established in 1990 in the Chin-Shan Community, a suburb 20
      miles outside of metropolitan Taipei, Taiwan. The long-term objective was to
      investigate the prospective impact on cardiovascular health in a society
      undergoing transition from a developing to a developed nation. This article
      presents the study design, selected baseline risk factors of cardiovascular
      diseases (CVD), and CVD events at the 5-year follow-up evaluation with an
      emphasis on sociodemographic differences. The multivariate logistic regression
      analyses revealed that white-collar individuals were more likely than blue-collar
      workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL
      C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2
      2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR =
      1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and
      CVD/sudden death, and at moderately higher risk for coronary artery disease and
      diabetes, although both these trends were not significant. Men were more likely
      than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they
      were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8).
      The risk of CVD/sudden death was higher for men than for women during the follow
      up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as
      a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%)
      use in men. In conclusion, individuals of higher socioeconomic status have a
      higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD
      events.

PMID- 10942868
TI  - Functional decline among older adults: comparing a chronic disease cohort and
      controls when mortality rates are markedly different.
AB  - In studies of functional status decline in older persons, the strategy for
      handling deaths during follow-up may influence policy implications. We compared
      301 older ESRD dialysis patients with 322 controls to determine whether
      functional decline over 3 years among dialysis patients exceeded that of "normal
      aging." We used two different statistical methods and, for each, compared results
      when deaths were excluded and then included in the analysis. Dialysis patients
      incurred a larger follow-up mortality rate and were more impaired at baseline.
      Findings based on functional transition over time, assessed by a nominal
      variable, were sensitive to whether or not deaths were included in the analysis.
      However, findings based on nonparametric methods for an ordinal scale (functional
      impairment) were not sensitive to whether or not deaths were included in the
      analysis. Analyzing data with and without deceased subjects may be the most
      comprehensive approach to comparing two cohorts over time.

PMID- 10942869
TI  - Meta-analysis of diagnostic tests for acute sinusitis.
AB  - To facilitate management of acute sinusitis, we conducted a meta-analysis of
      published studies comparing diagnostic tests for this disorder. Thirteen studies
      were identified through literature search. Based on sinus puncture/aspiration
      (considered most accurate), 49-83% of symptomatic patients had acute sinusitis.
      Compared with puncture/aspiration, radiography offered moderate ability to
      diagnose sinusitis (summary receiver operator curve [SROC] area, 0.83). Using
      sinus opacity or fluid as the criterion for sinusitis, radiography had
      sensitivity of 0.73 and specificity of 0.80. Studies evaluating ultrasonography
      revealed substantial variation in test performance. The clinical evaluation,
      particularly risk scores formally incorporating history and physical examination
      findings, had moderate ability to identify patients with positive radiographs
      (SROC area, 0.74). Many studies were of poor quality, with inadequately described
      test methods and unblinded test interpretation. In conclusion, acute sinusitis is
      common among symptomatic patients. Radiography and clinical evaluation
      (especially risk scores) appear to provide useful information for diagnosis of
      sinusitis.

PMID- 10942870
TI  - Test-retest reliability of an epidemiological instrument for Parkinson's disease.
AB  - Reliability testing was conducted on a survey instrument for a genetic
      epidemiological study of Parkinson's disease (PD). Information on demographics,
      medical history, places of residence, and occupations was collected. The
      instrument was administered to 11 pairs of siblings discordant for PD and then re
      administered after 4 weeks. Twenty of 22 (91%) subjects completed and returned
      the retest questionnaire. Overall reliability of the instrument was acceptable
      (kappa = 0.88). This instrument could be used to elicit reliable information from
      similar profiled subjects in future investigations.

PMID- 10942871
TI  - Examination of the factor structure of physical activity behaviors.
AB  - Multiple physical activity recommendations exist for behaviors that vary in type
      and intensity (e.g., vigorous physical activity, strengthening exercises,
      moderate physical activity). The present study examined underlying dimensions of
      physical activity behaviors and determined the extent to which factors correspond
      to national health recommendations. Fifteen variables were drawn from six self
      report measures and subjected to factor analysis with quartimax rotation.
      Participants were 547 university seniors (56% female; 60% Caucasian; mean age =
      25 years). TV watching, the only index of sedentary behavior, did not load highly
      with other items, and was analyzed separately. Three interpretable factors were
      found: variables related to vigorous physical activity loaded highly on Factor 1;
      flexibility and strengthening items loaded highly on Factor 2; and moderate and
      housework activity loaded highly on Factor 3. Factors corresponded closely to
      national recommendations. Unweighted factor scores and TV watching correlated
      significantly with physiological indicators of fitness, supporting construct
      validity.

PMID- 10942872
TI  - Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine
      (BrdU) and proliferating cell nuclear antigen (PCNA) assays.
AB  - Cell proliferation in the human colorectum can be measured using
      bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays.
      Using data from the National Cancer Institute's Polyp Prevention Trial, these two
      assays are compared using correlation coefficients and variance components
      analysis. Adjusting for fixed as well as for the random effects of between-biopsy
      and scoring variation, the estimated correlation is 0.46 for the log labeling
      index and 0.45 for log proliferative height. This is an estimate of the highest
      correlation that can be achieved by taking multiple biopsies scored by multiple
      scorers. For single biopsies, the estimated correlation is 0.16 and 0.10,
      respectively. There are significant differences between the variance components
      for the two assays. For example, for log labeling index, PCNA has a lower
      variation between biopsies than BrdU, but higher variation between scorings. When
      used in a clinical or epidemiological setting, it is important to take multiple
      biopsies at multiple time points.

PMID- 10942873
TI  - Abdominal adiposity and clustering of multiple metabolic syndrome in White, Black
      and Hispanic americans.
AB  - PURPOSE: The aim of this study was to evaluate the association of abdominal
      adiposity assessed by waist circumference (WC) with clustering of multiple
      metabolic syndromes (MMS) in White, Black and Hispanic Americans. MMS was defined
      as the occurrence of two or more of either hypertension, type 2 diabetes
      mellitus, dyslipidemia, hypertriglyceridemia or hyperinsulinemia. METHODS: The
      number of MMS and fasting insulin (a surrogate measure of MMS) were each used as
      dependent variables in gender-specific multiple linear regression models,
      adjusting for age, smoking and alcohol intake. The contribution of WC to
      interethnic differences in clustering of MMS and fasting insulin concentration
      was assessed in gender-specific linear regression models. The risk of MMS due to
      large waist was estimated by comparing odds ratio for men with WC >/= 102 cm with
      those with WC < 102, and women with WC >/= 88 cm with women with WC < 88 cm in
      the logistic regression model adjusting for age, smoking and alcohol intake.
      RESULTS: WC was positively and independently associated with clustering of MMS
      and increased fasting insulin concentration adjusting for age, smoking and
      alcohol intake in the three ethnic groups (p < 0.01). Black ethnicity was
      associated with clustering of MMS and fasting insulin concentration (p < 0.01).
      Hispanic ethnicity was also associated with clustering of MMS in men and
      associated with fasting insulin concentration in both men and women (p < 0.01).
      In both men and women, the risk of MMS clustering was strongly associated with
      increased WC in all ethnic groups independent of BMI. CONCLUSION: WC appears to
      be a marker for multiple metabolic syndromes in these ethnic groups. The results
      of this investigation lend support to the view that waist measurement should be
      considered as a clinical variable for assessing the risk of cardiovascular
      diseases.

PMID- 10942874
TI  - Reproducibility of resting blood pressure and heart rate measurements. The
      HERITAGE Family Study.
AB  - PURPOSE: This study determined the reproducibility of resting systolic and
      diastolic blood pressure, mean arterial pressure, and heart rate (the average of
      three measures/day). METHODS: The data were obtained on two separate days prior
      to an exercise training intervention in a sample of 822 subjects participating in
      the HERITAGE Family Study. The same protocol was conducted across three days in
      an intracenter quality control substudy, which included an additional 60
      subjects. RESULTS: Reproducibility estimates included technical error,
      coefficient of variation within subjects, and intraclass correlation with results
      expressed by sex, race, age, cuff size, BMI, and %fat. Since the data were
      collected across four Clinical Centers, the reproducibility estimates were also
      computed separately for each Center. The systolic, diastolic, and mean arterial
      blood pressures were highly reproducible with technical errors less than 5.1
      mmHg, coefficients of variation of less than 7. 0% and intraclass correlations >
      0.75. The heart rates were slightly less reproducible. These results were fairly
      consistent across subject populations and across all four Clinical Centers.
      CONCLUSION: It is concluded that within subject day-to-day variations are small
      compared to between subject variance for resting systolic, diastolic, and mean
      arterial blood pressure and heart rate at each of the Clinical Centers for all of
      the HERITAGE Family Study data. This makes it appropriate to pool the data and
      analyze it for changes subsequent to endurance exercise training and to determine
      the possible genetic basis for these changes.

PMID- 10942875
TI  - Ten-year follow-up for male twins divided into high- or low-risk groups for
      ischemic heart disease based on risk factors measured 25 years previously.
AB  - PURPOSE: To undertake medical follow-up in white males in the National Heart,
      Lung, and Blood Institute (NHLBI) twin study, previously divided on the basis of
      cardiovascular disease risk factors. METHODS: Tree structured survival analysis
      (TSSA) used at a mean age of 63 years to classify twins into high and low risk
      subgroups for ischemic heart disease (IHD) found that subjects at a mean age of
      48 years were at highest risk with high systolic blood pressures and low high
      density lipoprotein cholesterol levels. Low risk subjects had lower blood
      pressures, better pulmonary function tests, and a negative family history for IHD
      or low post load plasma glucose levels. Medical record review was performed ten
      years later at the 4th Examination of the NHLBI twin cohort conducted in 1995
      1997. RESULTS: The percentage of men in the NHLBI twin study who died nearly
      tripled (from 9.3% to 25.8%) in the ten-year period between the ages of 63 and 73
      years. Deaths have tended to remain higher in DZ than MZ twins (27.8% versus
      23.7%). At Exam 4, the relative risk of IHD (fatal or non-fatal) was 5.24 times
      higher for those in the high risk group than those in the low risk class (95%
      confidence limit 2.72-10.07, p < 0.0001 and 5.86 for any cardiovascular disease
      (95% confidence limit 3.03-11.33). The proportion of deaths from IHD in subjects
      with a high risk profile at entry was 51.7%, and 70.0% had died from all
      cardiovascular related disease. CONCLUSION: The present results indicate TSSA
      remained effective in classifying subjects into subgroups with greater risk of
      morbidity and mortality related to cardiovascular disease after ten additional
      years.

PMID- 10942876
TI  - A comparison of cervical pathology between United States Air Force women who did
      and did not serve in the Persian Gulf War.
AB  - PURPOSE: The purpose of this study was to look objectively at cervical
      cytological differences between women Gulf War female veterans (GWFV) and Gulf
      War-era active duty females not deployed to the Gulf (NDF) during Operation
      Desert Shield/Desert Storm using Pap smear results. METHODS: A cohort of 6715
      active duty Air Force women who also served on active duty between August 7, 1990
      March 1, 1991 provided at least one Pap smear as part of routine medical care
      during 1994. Of these, 1446 were identified as GWFV and 5269 were identified as
      NDF. Diagnoses were compared using Chi-square tests with Yate's continuity
      correction. RESULTS: There were no differences between the two groups, overall,
      in the diagnosis of other than within normal limits (OTWNL), the diagnoses of
      significant disease or in Bethesda system diagnoses in each of the three years
      for which comparisons were made. GWFV diagnosed in the 26-30 age group were
      significantly more likely to have a diagnosis of OTWNL than were NDF in the same
      age group in 1994. There were no differences between the two groups in any other
      age category. CONCLUSIONS: The data provide little support for the hypothesis
      that a difference exists between GWFV and NDF with respect to abnormal cervical
      cytology.

PMID- 10942877
TI  - Epidemiology of erectile dysfunction: a community-based study in rural New York
      State.
AB  - PURPOSE: Few published population-based studies that deal with the prevalence of
      erectile dysfunction (ED) involve rural populations. This study determined the
      prevalence and determinants of ED among a rural population. It also evaluated the
      relevance of some major predictors of help-seeking decisions. METHODS: A self
      administered survey was conducted by mail among 5198 randomly selected men 50-76
      years old, living in four rural counties in Central New York State. RESULTS: The
      response rate was 44.7% and the participation rate among respondents was 71.0%.
      Mean ages of men reporting and those not reporting ED were 64.5 7.2 and 59.8 7.2
      years respectively. The mean duration of self-reported ED was 4.9 4.6 years. The
      overall prevalence of ED was 46.3% while the minimum prevalence was estimated as
      21.3%. Age-specific prevalence was 26.0%, 34.9%, 46.9%, 57.8% and 69.4% among men
      50-54, 55-59, 60-64, 65-69, and 70-76 years old respectively. There was a
      statistically significant relationship between age, socio-economic status,
      perceived state of health and erectile function status (p < 0.001). However,
      socio-economic status, marital status, perceived state of health and age were not
      significant predictors of help-seeking decisions. CONCLUSIONS: The prevalence of
      ED among men 50-76 years old in rural Central New York State is at least 21.3%
      and may be as high as 46.3%. Age, perceived state of health and socio-economic
      status were found to be important determinants of erectile dysfunction among this
      population. For purposes of comparative analyses, future epidemiological studies
      should report both the overall and minimum rates among men with clinically
      relevant erectile dysfunction.

PMID- 10942878
TI  - Neighborhood poverty as a predictor of intimate partner violence among White,
      Black, and Hispanic couples in the United States: a multilevel analysis.
AB  - PURPOSE: This study assessed the contribution of neighborhood poverty, measured
      at the census tract level, to the risk of male-to-female and female-to-male
      partner violence (MFPV, FMPV) among white, black, and Hispanic couples in the
      United States. METHODS: As part of the 1995 National Alcohol Survey, a
      representative sample of married/cohabiting couples was obtained through a
      multistage, multicluster household probability sampling frame. The outcome
      variables, MFPV and FMPV, were measured through the Conflict Tactics Scale, Form
      R. Sociodemographic, psychosocial, and alcohol consumption covariates that were
      statistically significant through bivariate analysis were retained as individual
      level predictors. Neighborhood poverty, indicating residence in a census tract
      where greater than 20% of the population lived below the Federal poverty line,
      was assessed by appending 1990 Census data to the primary data set. Multilevel
      logistic regression models were constructed, with separate analyses performed for
      each outcome (MFPV, FMPV) among the white, black, and Hispanic couples. RESULTS:
      Couples residing in impoverished neighborhoods are at increased risk for both
      MFPV and FMPV. The association between residence in an impoverished neighborhood
      and MFPV was statistically significant for black couples (Odds Ratio [OR] 2.87;
      95% Confidence Interval [CI] 1.36, 6.07). The association between residence in an
      impoverished neighborhood and FMPV was statistically significant for black
      couples and white couples. CONCLUSIONS: Characteristics of the socioenvironment,
      such as neighborhood poverty, are associated with the risk of partner violence,
      particularly among black couples. Policies aimed at reducing community poverty
      may contribute to effective partner violence prevention strategies.

PMID- 10942880
TI  - Puberty-associated differences in total cholesterol and triglyceride levels
      according to sex in French children aged 10-13 years.
AB  - PURPOSE: To assess the relationships between lipid levels and sexual maturity,
      independently of age-related differences, and to investigate possible differences
      related to sexual maturity across the percentiles of the lipid distributions.
      METHODS: Fasting serum total cholesterol and triglyceride concentrations were
      measured in 6577 boys and 6605 girls, aged from 10 to 13 years, with different
      Tanner stages. The total cholesterol and triglyceride mean and percentile levels
      were estimated according to age and Tanner stage by ordinary least squares and
      percentile regression models, separately in both sexes. RESULTS: In boys and
      girls, total cholesterol levels were significantly associated with pubertal stage
      after controlling for age. At age 12, the estimated mean levels in boys varied
      from 4.82 mmol/L for Tanner 1 to 4.41 for Tanner 5. The corresponding values were
      5.05 and 4.62 mmol/L in girls, for whom the association with maturity was
      stronger in the upper than in the lower percentiles (p < 0.0001); between the
      extreme Tanner stages, the 95th percentiles of total cholesterol differed by 0.80
      mmol/L, in comparison to 0.19 mmol/L for the 5th percentiles. Therefore, 1. 8% of
      girls and 0.7% of boys were classified differently whether Tanner stage was used
      or not to assess hypercholesterolemia (concentrations in the upper 5% of the
      distributions). Triglycerides were positively related to sexual maturity
      independently of age, but the discrepancies between classifications were lower;
      1.1% in girls and 0.4% in boys. CONCLUSIONS: Our findings emphasize the
      importance of sexual maturity, even for a given age, for interpreting lipid
      levels in children.

PMID- 10942879
TI  - Segregation analysis of drinking problem in elderly men and their first-degree
      relatives from the Western Collaborative Group Study.
AB  - PURPOSE: The purpose of this study is to determine the mode of inheritance of
      alcohol-related drinking problems. METHODS: Family history was collected by
      interview from 493 elderly male participants (probands) in a follow-up
      cardiovascular exam of healthy white men living in the San Francisco Bay Area and
      Los Angeles. Segregation analysis was used to test for the presence of a major
      gene effect underlying the liability to develop an alcohol-related drinking
      problem. RESULTS: The results showed that the liability to drinking problem is
      due, in part, to a single major gene with no residual effects from shared
      familial influences. CONCLUSIONS: These results suggest that at least one major
      gene is involved in the genetic predisposition to develop drinking problem in
      late adulthood.

PMID- 10942881
TI  - Differences in echocardiographic findings and systemic hemodynamics among non
      diabetic American Indians in different regions: The Strong Heart Study.
AB  - PURPOSE: This study was undertaken to determine whether differences in left
      ventricular (LV) and systemic hemodynamic findings exist between American Indians
      in different regions that might contribute to known differences in cardiovascular
      morbidity rates among American Indians. METHODS: We compared echocardiography
      results in 290 non-diabetic Strong Heart Study (SHS) participants in Arizona, 595
      in Oklahoma and 572 in North/South Dakota (ND/SD). RESULTS: Participants in the 3
      regions were similar in age and gender but those in Arizona had the highest body
      mass indices and lowest heart rates while those in ND/SD had the lowest diastolic
      blood pressures (BP). In analyses that adjusted for significant covariates, ND/SD
      participants had larger aortic (Ao) anular, Ao root, and LV chamber size as well
      as higher cardiac output and lower peripheral resistance, whereas Arizona
      participants had increased LV wall thickness and mass and reduced LV myocardial
      contractility. These findings may contribute to the known high rates of
      cardiovascular events in ND/SD Indians and to the proportionately higher rate of
      cardiovascular death than of non-fatal cardiovascular events that has been
      recently documented in Arizona Indians. CONCLUSIONS: Application of
      echocardiography to non-diabetic SHS participants reveals that LV chamber and
      arterial size are larger in ND/SD Indians and that LV wall thicknesses and mass
      are higher and LV myocardial contractility lower in Arizona Indians, possibly
      contributing to the higher than expected rates of cardiovascular morbidity and
      mortality among Indians in Arizona.

PMID- 10942882
TI  - A fifty year mortality follow-up study of veterans exposed to low level chemical
      warfare agent, mustard gGas.
AB  - PURPOSE: To determine if there is an increased risk of any cause specific
      mortality associated with low level mustard gas exposure among World War II Navy
      veterans. METHODS: A retrospective mortality follow-up study was conducted
      comparing the mortality of World War II Navy veterans who received low-level non
      lethal exposures of mustard gas to that of World War II Navy veterans who were
      not exposed. This study identified 1545 Navy recruits stationed at Bainbridge,
      Maryland, between 1944-1945, who voluntarily participated in mustard gas chamber
      tests. These veterans were exposed to mustard gas while wearing protective
      clothing and masks. Control veterans consisted of 2663 Navy veterans who served
      at the same location and time as the exposed, but did not participate in chamber
      tests. Cause specific mortality risks associated with mustard gas exposure and
      level of mustard gas exposure were examined using adjusted and unadjusted
      relative risk estimates. RESULTS: There was no excess of any cause specific
      mortality associated with varying levels of mustard gas exposures among Navy
      veterans subject to the chamber tests. CONCLUSIONS: The levels of mustard gas
      exposures experienced by World War II veterans, which were sufficient to cause
      skin reactions (erythema, vesicles, and ulceration), were not associated with any
      increased risk of cause specific mortality.

PMID- 10942883
TI  - Light-induced rod and cone cell death and regeneration in the adult albino
      zebrafish (Danio rerio) retina.
AB  - Light-induced photoreceptor cell degeneration has been studied in several
      species, but not extensively in the teleost fish. Furthermore, the continual
      production of rods and cones throughout the teleost's life may result in
      regeneration of lost rods and cones. We exposed adult albino zebrafish to 7 days
      of constant darkness, followed by 7 days of constant 8000 lux light, followed by
      28 days of recovery in a 14-h light:10-h dark cycle. We characterized the
      resulting photoreceptor layer cell death and subsequent regeneration using
      immunohistochemistry and light microscopy. Within the first 24 h of constant
      light, the zebrafish retina exhibited widespread rod and cone cell apoptosis.
      High levels of cell proliferation within the inner nuclear layer (INL) were
      observed within the first 3 days of constant light, as assessed by
      immunodetection of proliferating cell nuclear antigen and BrdU labeling. The
      proliferating cells within the INL were closely associated with the radial
      processes of Muller glia, similar to the pluripotent retinal stem cells observed
      during embryonic development. Using antibodies generated against the individual
      zebrafish opsins, we determined that rods and the green, blue, and ultraviolet
      cone cells were replaced within the 28 day recovery period. While both rods and
      cones were replaced, the well-ordered cone cell mosaic was not reestablished.

PMID- 10942884
TI  - Interaction of BDNF and testosterone in the regulation of adult perineal
      motoneurons.
AB  - In androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus
      (SNB), we investigated the interaction of BDNF (brain-derived neurotrophic
      factor) and testosterone to understand whether each factor gates the ability of
      the other to regulate androgen receptor expression and soma size, and whether
      each factor requires the presence of the other for its action. We axotomized SNB
      motoneurons and applied BDNF or PBS (phosphate-buffered saline) to the cut ends
      of the axons in rats that were castrated and treated with either testosterone or
      placebo. Control groups were either not castrated or not axotomized, or had
      intact SNB axons and were castrated and treated with testosterone or placebo. We
      found that testosterone determined the expression of nuclear androgen receptor,
      and this effect was enhanced by both BDNF and contact with the target muscles.
      The effect of BDNF on androgen receptor expression was seen only when
      testosterone was present. In the regulation of soma size, BDNF dominated. The
      application of BDNF completely compensated for the loss of testosterone in
      castrated males so that the testosterone effect on soma size was seen only in
      intact SNB motoneurons and in axotomized motoneurons treated with PBS. Moreover,
      testosterone increased androgen receptor and soma size in axotomized SNB
      motoneurons, indicating that testosterone can act on sites other than the target
      muscles of the SNB to regulate each of these. These results indicate that the
      regulation of androgen receptor by testosterone does not require BDNF, but the
      regulation of androgen receptor by BDNF does require testosterone. The regulation
      of soma size by BDNF does not require high expression of nuclear androgen
      receptor.

PMID- 10942885
TI  - Protein expression patterns of identified neurons and of sprouting cells from the
      leech central nervous system.
AB  - It has previously been shown that cephalic, segmental, and caudal ganglia from
      the medicinal leech show differences in their protein composition. Here we
      studied whether the neuronal reorganization that occurs in cultured segmental
      ganglia from the medicinal leech is accompanied by detectable changes in the
      protein expression pattern. Using silver-stained two-dimensional gels we showed
      that after 5 and 12 days in culture changes in the protein patterns can be
      detected in isolated ganglia. The changes observed in the two-dimensional gels
      occurred concomitantly with a sprouting of serotoninergic neurites and a
      decreased transmitter content of dopaminergic neurites as shown by using the
      glyoxylic acid condensation reaction. In addition, we present evidence that
      Retzius cells, which can be identified by their characteristic morphology and
      action potential waveform, exhibit biochemically unique properties with respect
      to their protein expression pattern.

PMID- 10942886
TI  - The distribution and developmental regulation of NMDA receptor subunit proteins
      in the outer and inner retina of the rat.
AB  - In order to investigate whether N-methyl-D-aspartate (NMDA) receptors with
      distinct pharmacological properties are differentially distributed within the
      retinal layers, the spatial distribution and temporal regulation of all NMDA
      receptor subunits was analyzed in parallel on the protein level in the rat retina
      during development. Immunohistochemistry was performed on retinal sections at
      different developmental ages between embryonic (E) days 20/21 and the adult stage
      using specific antibodies against NMDA subunits (NR1, NR2A-D). All NMDA subunits
      were expressed in the rat retina postnatally but showed different spatial
      patterns. In particular, and in contrast to previous in situ hybridization
      studies, labeling of NR2 subunits was observed in horizontal cell bodies and in
      the outer plexiform layer, indicating that functional NMDA receptors are
      expressed in this retinal cell type in the rat. Expression of NR2D was restricted
      to the inner retina and seemed to be involved in neurotransmission within the rod
      pathway. In the inner plexiform layer (IPL), distinct patterns of labeling were
      observed for different NMDA subunits. NR1 was found in two bands which can be
      related to the off- and on-signal pathways, whereas NR2A and NR2B were located in
      two bands within the off-sublaminae of the IPL. The antibody against NR2C was
      distributed throughout the whole IPL, and NR2D was expressed exclusively in the
      innermost part of the IPL where rod bipolar cell terminals terminate. Distinct
      bands of immunoreactivity in the IPL were observed only from P14 on. In
      conclusion, there are clear differences in the spatial distribution and temporal
      expression of NMDA receptor subtypes in the rodent retina. This indicates that
      specific retinal cells selectively express glutamate receptors composed of
      different subunit combinations and thus display different pharmacological and
      kinetic properties.

PMID- 10942887
TI  - Reciprocal interactions between perisynaptic Schwann cells and regenerating nerve
      terminals at the frog neuromuscular junction.
AB  - The perisynaptic Schwann cell (PSC) has gained recent attention with respect to
      its roles in synaptic function, remodeling, and regeneration at the vertebrate
      neuromuscular junction (NMJ). Here we test the hypothesis that, following nerve
      injury, processes extended by PSCs guide regenerating nerve terminals (NTs) in
      vivo, and that the extension of sprouts by PSCs is triggered by the arrival of
      regenerating NTs. Frog NMJs were double-stained with a fluorescent dye, FM4-64,
      for NTs, and fluorescein isothiocyanate (FITC)-tagged peanut agglutinin (PNA) for
      PSCs. Identified NMJs were imaged in vivo repeatedly for several months after
      nerve injury. PSCs sprouted profusely beginning 3-4 weeks after nerve transection
      and, as reinnervation progressed, regenerating NTs closely followed the preceding
      PSC sprouts, which could extend tens to hundreds of microns beyond the original
      synaptic site. The pattern of reinnervation was dictated by PSC sprouts, which
      could form novel routes joining neighboring junctions or develop into new
      myelinated axonal pathways. In contrast to mammals, profuse PSC sprouting in frog
      muscles was not seen in response to axotomy alone, and did not occur at
      chronically denervated NMJs. Instead, sprouting coincided with the arrival of
      regenerating NTs. Immunofluorescent staining revealed that in muscle undergoing
      reinnervation 4 weeks after axotomy, 91% of NMJs bore PSC sprouts, compared to
      only 6% of NMJs in muscle that was chronically denervated for 4 weeks. These
      results suggest that reciprocal interactions between regenerating NTs and PSCs
      govern the process of reinnervation at frog NMJs: regenerating NTs induce PSCs to
      sprout, and PSC sprouts, in turn, lead and guide the elaboration of NTs.

PMID- 10942889
TI  - Matrix metalloproteinase-3 removes agrin from synaptic basal lamina

PMID- 10942888
TI  - Effects of gonadal steroids during pubertal development on androgen and estrogen
      receptor-alpha immunoreactivity in the hypothalamus and amygdala.
AB  - Perinatal development is often viewed as the major window of time for
      organization of steroid-sensitive neural circuits by steroid hormones. Behavioral
      and neuroendocrine responses to steroids are dramatically different before and
      after puberty, suggesting that puberty is another window of time during which
      gonadal steroids affect neural development. In the present study, we investigated
      whether the presence of gonadal hormones during pubertal development affects the
      number of androgen receptor and estrogen receptor alpha-immunoreactive (AR-ir and
      ER alpha-ir, respectively) cells in limbic regions. Male Syrian hamsters were
      castrated either before or after pubertal development, and 4 weeks later they
      received a single injection of testosterone or oil vehicle 4 h prior to tissue
      collection. Immunocytochemistry for AR and ER alpha was performed on brain
      sections from testosterone-treated and oil-treated males, respectively. Adult
      males that had been castrated before puberty had a greater number of AR-ir cells
      in the medial preoptic nucleus than adult males that had been castrated after
      puberty. There were no significant differences in ER alpha-ir cell number in any
      of the brain regions examined. The demonstration that exposure to gonadal
      hormones during pubertal development is associated with reduced AR-ir in the
      medial preoptic nucleus indicates that puberty is a period of neural development
      during which hormones shape steroid-sensitive neural circuits.

PMID- 10942890
TI  - Simultaneous estimation of T(G2+M), T(S), and T(pot) using single sample dynamic
      tumor data from bivariate DNA-thymidine analogue cytometry.
AB  - BACKGROUND: Estimating the duration of S phase (T(S) ) and the potential doubling
      time (T(pot) ) from a single time measurement of the movement of cells using
      bivariate cytometry is common. However, these estimates require an assumption of
      the duration of G2 + M (T(G2+M) ). Inspection of the measured dynamic quantities,
      relative movement [RM(t)], fractions of labeled divided and undivided cells
      (f(lu)(t) and f(ld)(t)) suggests that T(G2+M), T(S), and T(pot) can be determined
      simultaneously. METHODS: An equation connecting the growth of the cell
      population, time, and the dynamic quantities was determined. The equation cannot
      be solved analytically, but accurate approximations can be used to find T(pot).
      From this result, the value of T(G2+M) can be determined from f(ld)(t), and T(S)
      can be determined from RM(t). RESULTS: Kinetic parameters obtained from single
      time estimates using the new method compared to those obtained from the analysis
      of multiple time-point measurements of MCa-K and MCa-4 murine tumors are shown to
      be in close agreement. Moreover, estimates of T(G2+M) in MCa-4 tumors, treated
      with paclitaxel, provide extra information on the changes in T(G2+M). When
      applied to the rat R3327-G prostate tumor model following androgen ablation, a
      correlation analysis of the T(pot) values obtained by the new and previous single
      time-point methods demonstrates that the rank order from shortest to longest
      T(pot) values are largely preserved. CONCLUSIONS: The new procedure makes direct
      estimation of T(G2+M) possible from single time-dynamic measurements. The results
      from previous studies on T(S) and T(pot) are largely unchanged, but extra
      information is now available.

PMID- 10942891
TI  - Lymphoma discrimination by computerized triple matrix analysis of list mode data
      from three-color flow cytometric immunophenotypes of bone marrow aspirates.
AB  - BACKGROUND: The goal of this study was to evaluate a self-learning algorithm for
      the computer classification of information extracted from flow cytometric
      immunophenotype list mode files from high-grade non-Hodgkin's lymphoma (NHL),
      Hodgkin's disease (HD), and multiple myeloma (MM). Materials and Methods Bone
      marrow aspirates (BMA) were obtained from untreated NHL (n = 51), HD (n = 9), or
      MM (n = 13) patients. Bone marrow aspirates were not infiltrated in NHL and HD
      patients as confirmed by thorough histologic and cytologic investigation;
      however, MM patients showed an infiltration rate >50% by malignant myeloma cells.
      Peripheral blood leukocyte (PBL) samples were taken from age-matched healthy
      volunteers (n = 44) as easily available control material. A second control group
      of 15 healthy volunteers, from whom BMA and PBL samples were available, allowed
      us to differentiate whether the observed classification results on malignant
      samples were due to the malignant process or simply to the inherent differences
      between BMA and PBL. Bone marrow aspirates and PBL were analyzed by the same
      immunophenotyping antibody panel (CD45/14/20, CD4/8/3, kappa/CD19/5,
      lambda/CD19/5). The acquired list mode data files were analyzed and classified by
      the self-learning triple matrix classification algorithms CLASSIF1 following a
      priori separation of the data into a learning set and unknown test set. After
      completion of the learning phase, known patient samples were reclassified and
      unknown samples prospectively classified by the algorithm. RESULTS: Highly
      discriminatory information was extracted for the various lymphoma entities. The
      most discriminating information was encountered in antibody binding, antibody
      binding ratios, and relative antibody surface density parameters of leukocytes
      rather than in percentage frequencies of discrete leukocyte subpopulations.
      Samples from healthy controls were classified as normal in 97.2% of the cases,
      whereas those of NHL, HD, and MM patients were on average correctly classified in
      80. 8% of the cases. CONCLUSIONS: Although no detectable lymphoma cells were
      present in BMA of NHL and HD patients, the CLASSIF1 classification of the
      immunophenotypes of morphologically normal cells provided a surprisingly good
      disease discrimination equal or better than that obtained by examining
      pathological lymph nodes according to the respective literature. The results are
      suggestive for a lymphoma-related and disease-specific antigen expression shift
      on normal hematopoietic bone marrow cells that can be used to discriminate the
      underlying disease (specificity of unspecific changes), i.e., in this case NHL
      from HD. Multiple myeloma patients were discriminated by changes on malignant as
      well as on normal bone marrow cells.

PMID- 10942892
TI  - Quantitative study of dynamic behavior of cell monolayers during in vitro wound
      healing by optical flow analysis.
AB  - BACKGROUND: In vitro wound healing assays are experimental models commonly used
      to analyze cell behavior during the migration process. A new approach is proposed
      for the quantification of cell motility based on an optical flow method. METHODS:
      We assumed that cell-population dynamics can be defined by an a priori affine
      motion model. Identified model parameters are used as motion descriptors
      quantifying both elementary and complex cell movements, either at the wound
      margins or within the cell monolayer. RESULTS: When compared with the estimation
      of cell motility calculated from wound area temporal variation, it allows a more
      detailed and precise characterization of cell population movements. Comparative
      analysis of normal and cancerous cell lines revealed that typical measured
      velocities were about 2 microm/h and 7 microm/h for L929 and HeLa cells,
      respectively, at the beginning of the wound closure. The quantification of the
      effect of Hoechst 33342 on cell dynamics showed a similar behavior for control
      and stained cells within 20 h after wound scratching, but then a decreased
      velocity of stained cells. CONCLUSIONS: The results demonstrate that this
      approach can be used to gain new insights into the dynamic changes induced by the
      extracellular environment and by anticancer drugs.

PMID- 10942893
TI  - Efficient generation of stably electrotransfected human hematopoietic cell lines
      without drug selection by consecutive FACsorting.
AB  - BACKGROUND: Current methods to establish stably transfected cell lines by
      nonviral techniques involve coselection for a drug selection marker. However,
      this approach suffers from several drawbacks. We developed a fluorescence
      activated cell sorting (FACS)-based protocol for the selection and isolation of
      stable hematopoietic electrotransfectants without the need for selective growth
      conditions. METHODS: Leukemic K562 cells were electroporated with the enhanced
      green fluorescent protein (EGFP) reporter gene and FACsorted to obtain stably
      EGFP-expressing cells. Stable EGFP(+) clones were established by single-cell
      sorting. RESULTS: Efficiency of stable EGFP gene expression increased steadily in
      function of number of consecutive FACsorts. Stable transfectants (>99% EGFP(+))
      were obtained after four FACsorts. Furthermore, several single-cell derived
      clones with variable levels of stable EGFP expression were isolated and cultured
      without the use of selective growth media. CONCLUSIONS: EGFP is an effective
      selection marker for the generation and isolation of stably transfected
      hematopoietic cell clones without the need for selection in toxic media that
      could create a potentially undesirable stress environment for stably transfected
      cells.

PMID- 10942894
TI  - Use of fluorescence genomic in situ hybridization (GISH) to detect the presence
      of alien chromatin in wheat lines differing in nuclear DNA content.
AB  - BACKGROUND: Many times small differences in genome size are reported between or
      within plant species in which no cytologic confirmation is made. Attempts to
      repeat these studies have met with limited success. The controversy then becomes
      whether or not these small differences that were not confirmed cytologically are
      real. The present study was undertaken to determine if the approximately 1%
      nuclear variation seen by flow cytometry among wheat lines selected for aluminum
      response was due to actual chromatin differences. METHODS: The three parental
      wheat cultivars used in the aluminum selection along with the isolines resulting
      from the selection were analyzed. One parental line had previously been reported
      to have alien chromatin substituted for the corresponding wheat homologous
      chromatin. Genomic in situ hybridization was used to determine the presence or
      absence of rye chromatin in three cultivars and six near-isolines of wheat.
      RESULTS: Upon observing metaphase chromosomes of the Century parent and its
      isolines, two of the chromosomes were observed to be one-half yellow-orange,
      indicating rye chromatin with the remaining portion of the chromosomes and the
      other 40 wheat chromosomes having no label indicating wheat chromatin. In the
      Chisholm parent and its isolines, none of the chromosomes were labeled,
      indicating the absence of rye chromatin. In addition, none of the third parents'
      chromosomes had the rye yellow-orange signal. CONCLUSIONS: The wheat lines with
      the larger DNA contents were observed to have alien DNA present. DNA differences
      between the normal wheat chromosomes and the substituting alien chromatin were
      calculated based on total chromosome length. The increase in genome size of the
      wheat lines containing the alien chromatin appears to be the result of the alien
      chromatin having approximately 43% more DNA than the wheat chromatin it is
      replacing. Thus, the small DNA difference previously reported by flow cytometry
      was demonstrated to be a real DNA variation due to the presence of small
      fragments of alien chromosomes added to the wheat genome.

PMID- 10942895
TI  - Individual Escherichia coli cells studied from light scattering with the scanning
      flow cytometer.
AB  - BACKGROUND: Flow cytometry is a powerful tool for the analysis of individual
      particles in a flow. Differential light scattering (an indicatrix) was used for
      many years to obtain morphologic information about microorganisms. The
      indicatrices play the same role for individual particle recognition as a spectrum
      for substance characterization. We combined two techniques to analyze the
      indicatrix of the cells for the purpose of developing a database of light
      scattering functions of cells. METHODS: The scanning flow cytometer (SFC) allows
      the measurement of the entire indicatrix of individual particles at polar angles
      ranging from 5 degrees to 100 degrees. In this work, light-scattering properties
      of Escherichia coli have been studied both experimentally and theoretically with
      the SFC and the T-matrix method, respectively. The T-matrix method was used
      because of the nonspherical shape of E. coli cells, which were modeled by a
      prolate spheroid. RESULTS: The indicatrices of E. coli cells were stimulated with
      T-matrix method at polar angles ranging from 10 degrees to 60 degrees. The
      absolute cross-section of light scattering of E. coli has been determined
      comparing the cross section of polystyrene particles modeled by a homogeneous
      sphere. The E. coli indicatrices were compared for logarithmic and stationary
      phases of cell growth. CONCLUSIONS: The indicatrices of E. coli were reproducible
      and could be used for identification of these cells in biologic suspensions. The
      angular location of the indicatrix minimum can be used in separation of cells in
      logarithmic and stationary phases. To use effectively the indicatrices for that
      purpose, the light-scattering properties of other microorganisms have to be
      studied.

PMID- 10942896
TI  - Actin assembly induced by polylysine beads or purified phagosomes: quantitation
      by a new flow cytometry assay.
AB  - BACKGROUND: Actin assembly on biological membranes is a poorly understood
      process. We have previously shown that phagosomal membranes could induce actin
      assembly in the presence of thymosin beta4 (an actin sequestering protein that
      inhibits nonspecific nucleation), via the barbed ends of actin filaments.
      METHODS: Here, we have developed an in vitro system based on fluorescein-labeled
      G (monomeric) actin and flow cytometry analysis, which allowed us to quantify de
      novo actin assembly on the cytoplasmic side of purified phagosomes. To
      standardize the system, we also used latex beads covalently coupled with
      polylysine, which efficiently promote actin nucleation. RESULTS: Flow cytometry
      analysis showed that the percentage of polylysine beads positive for F-actin
      filaments increased in a time- and G-actin concentration-dependent manner.
      Incubation of phagosomes with reagents affecting actin dynamics allowed us to
      extend our previous data showing that the phagosomal membranes assemble actin
      filaments de novo. Finally, our results pin-point a potential role for gelsolin
      as a positive regulator of actin assembly on the phagosomal membrane.
      CONCLUSIONS: We propose that our system could facilitate the development of other
      in vitro assays for the analysis of actin assembly and its links to signaling in
      cells.

PMID- 10942897
TI  - Optimization of cell permeabilization for multiparametric flow cytometric
      analysis with lectin staining.
AB  - BACKGROUND: This study was undertaken in mice to develop a reproducible procedure
      of cell permeabilization, allowing intracellular protein staining by
      immunofluorescence (i.e., Bcl-2) without losing surface labeling especially for
      lectins (i.e., B220 and peanut agglutinin [PNA]). This article reports results
      obtained with different permeabilization protocols. METHODS: Lymphoid cells were
      extracted and prepared from Peyer's patches and spleen. After surface labeling
      using anti-B220-Cy-chrome and PNA-biotin/streptavidin-phycoerythrin, we
      comparatively tested three permeabilization protocols: saponin 0.3%, methanol
      70%, and the commercial kit Dako Intrastain. Final Bcl-2 staining was performed
      and cells were analyzed by flow cytometry. RESULTS: With 0.3% saponin as the
      permeabilization reagent, a significant loss of lectin labeling was observed when
      comparing mono PNA and triple (i.e. , B220-PNA-Bcl-2) staining (74.8% and 22.5%
      positive cells, respectively). Quality of PNA staining was conserved with
      Intrastain when comparing multiparametric versus monoparametric stainings (82. 4%
      of positive cells versus 78.3%, respectively). Intrastain preserved scatter
      characteristics (69.9% of total cells in the lymphocyte gate with Intrastain
      versus 13.7% with saponin 0.3% and 20.9% with methanol 70%). This protocol has
      been used for a preliminary multiparametric analysis in order to quantify Bcl-2
      expression in PNA/B220-positive cells. CONCLUSION: This protocol may be useful to
      assess simultaneously lectin cell surface labeling and intracellular target
      staining.

PMID- 10942898
TI  - Modulation of daunorubicin cellular resistance by combination of P-glycoprotein
      blockers acting on drug efflux and intracellular drug sequestration in Golgi
      vesicles.
AB  - BACKGROUND: S9788 and PSC833 were developped as P-glycoprotein (Pgp) blockers and
      found to act additionally on daunorubicin subcellular distribution, involving
      different putative targets. On this basis, combinations of S9788 and PSC833 were
      evaluated in Pgp-expressing MCF7(DXR) cells in which we recently demonstrated
      that daunorubicin was sequestered in Golgi vesicles (Bour-Dill et al.: Cytometry,
      39: 16-25, 2000). METHODS: Combinations of S9788 and PSC833 consisted in
      complementary fractions of iso-effective concentrations (IEC) leading to 90%
      (IEC90) and median (IEC50) reversion of daunorubicin resistance. Resistance
      modulation was assessed using cytotoxicity assays, flow cytometry determination
      of intracellular daunorubicin, and fluorescence microscopy analysis of
      daunorubicin subcellular distribution. RESULTS: Individually, both S9788 and
      PSC833 were found to be very potent with IEC90 of 5 and 15 micromol/l, and IEC50
      of 0.1 and 0.2 micromol/l, respectively, for S9788 and PSC833. When combined,
      synergistic cytotoxicity was observed for both IEC90 and IEC50 combinations while
      intracellular daunorubicin fluorescence was only synergistically increased for
      IEC90 combinations. For IEC50 combinations, no increase in intracellular
      fluorescence was observed, and fluorescence microscopy examination of the cells
      suggested that daunorubicin sequestration in Golgi vesicles could be modulated at
      concentrations that do not significantly increase daunorubicin cellular
      concentration. Using immunofluorescence and reverse transcription-polymerase
      chain reaction analyses, multidrug resistance-associated protein, major vault
      lung-resistance protein, and anthracycline-resistance associated protein were not
      found to be implicated. CONCLUSIONS: Synergistic combinations of S9788 and PSC833
      might offer alternative ways to decrease the toxicity generated by high-dose Pgp
      blockers without altering the efficacy of the resistance modulation.

PMID- 10942899
TI  - Distinction between HLA class I-positive and -negative cervical tumor
      subpopulations by multiparameter DNA flow cytometry.
AB  - BACKGROUND: The study of the molecular-genetic basis of heterogeneity of HLA
      class I expression in solid tumors is hampered by the lack of reliable rapid cell
      by-cell isolation techniques. Hence, we studied the applicability of a flow
      cytometric approach (Corver et al.: Cytometry 2000;39;96-107). METHODS: Cells
      were isolated from five fresh cervical tumors and simultaneously stained for CD45
      or vimentin (fluorescein isothiocyanate fluorescence), Keratin (R-phycoerythrin
      fluorescence), HLA class I (APC fluorescence), and DNA (propidium iodide
      fluorescence). A dual-laser flow cytometer was used for fluorescence analysis.
      Tissue sections from the corresponding tumors were stained for HLA class I
      antigens, keratin, vimentin, or CD45. RESULTS: Flow cytometry enabled the
      simultaneous measurement of normal stromal cells (vimentin positive),
      inflammatory cells (CD45 positive), epithelial cells (keratin positive), and DNA
      content readily. Normal stromal/inflammatory cells served as intrinsic HLA class
      I-positive as well as DNA-diploid references. Good DNA histogram quality was
      obtained (average coefficient of variation < 4%). Intratumor keratin positive
      subpopulations differing in HLA class I expression as well as DNA content could
      be clearly identified. Losses of allele-specific HLA class I expression found by
      immunohistochemistry were also detected by flow cytometry. CONCLUSIONS: We
      conclude that multiparameter DNA flow cytometry is a powerful tool to study loss
      of HLA class I expression in human cervical tumors. The method enables flow
      sorting of discrete tumor and normal cell subpopulations for further molecular
      genetic analysis.

PMID- 10942901
TI  - Cytogenetic monitoring of cardiology unit hospital workers exposed to Doppler
      ultrasound.
AB  - We studied the effects of ultrasound on the peripheral blood lymphocytes of
      medical personnel from a cardiology unit working with colour Doppler ultrasonic
      equipment. Cytogenetic risks from ultrasound exposure were assessed by analysis
      of chromosome aberrations, sister chromatid exchanges (SCE), study of cell-cycle
      kinetics and micronucleus assay. We found significant increases (P < 0.001) in
      the total number of chromosome aberrations, mainly due to chromatid breaks and
      acentric fragments, increases in the total number of micronuclei and SCE and
      disturbances in cell-cycle kinetics in the exposed group compared to the control.
      In spite of their limitations, the results of the present investigation indicate
      that individuals occupationally exposed to ultrasound may experience an increased
      genotoxic risk and strongly emphasize the need for more research into the nature
      and extent of the biological consequences to medical personnel working with
      Doppler ultrasound.

PMID- 10942900
TI  - L-lactate protects in vitro acetylcholinesterase (AChE) from inhibition by
      paraoxon (E 600).
AB  - Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of
      serine hydrolases, is frequent. Oximes are the only enzyme reactivators
      clinically available. Recent work has shown that lactate is able to reduce in
      vitro the POX effects on butyrylcholinesterase (BChE). Most of the acute clinical
      symptoms, however, are caused by inhibition of acetylcholinesterase (AChE).
      Effects of lactate on the inhibition of AChE by POX were assessed in vitro in
      plasma of 12 (six male, six female) healthy human volunteers. The determinations
      were repeated using different lactate and different POX concentrations. The AChE
      activity determinations were performed in the following settings: (BL) baseline
      (untreated plasma); (a) after addition of POX to plasma (pl + POX); (b) after POX
      and plasma were incubated and then lactate was added (pl + POX/lact); (c) after
      addition of lactate to plasma (pl + lact); (d) after lactate and plasma were
      incubated and then POX was added (pl + lact/POX); (e) after lactate and POX were
      incubated and then added to plasma (lact + POX/pl). In the micro- and millimolar
      ranges, lactate is able to protect in vitro AChE from inhibition by POX when
      added to human plasma prior to POX or when incubated with POX prior to addition
      to plasma. Lactate added to plasma after POX has no protective effect. In a
      second set of experiments, the effect of lactate on AChE activity was determined.
      At high millimolar concentrations, lactate itself inhibits AChE non-competitively
      (mixed inhibition) to an extent comparable to POX (inhibition constant K(I) = 254
      mM).

PMID- 10942902
TI  - Modification of the proteinase/anti-proteinase balance in the respiratory tract
      of Sprague-Dawley rats after single intratracheal instillation of benzo[A]pyrene
      coated onto Fe(2)O(3) particles.
AB  - Available data suggest that repeated concurrent exposure to haematite (Fe(2)O(3))
      and benzo[A]pyrene (B[A]P) results in a decreased latency and an increased
      incidence of lung tumours in rodents compared to exposure to B[A]P alone.
      Moreover, the reactive oxygen species (ROS) formed by the lung cells themselves
      and/or by activated inflammatory cells may possibly contribute to the development
      of pulmonary disorders such as cancer formation. In order to investigate the
      precise role of iron in the injury induced by B[A]P-coated onto Fe(2)O(3)
      particles, we tend to address the hypothesis that Fe(2)O(3) and B[A]P, alone or
      in association, can induce oxidative stress conditions (malondialdehyde) and/or
      inflammatory reactions (interleukin-6) and thereby disrupt the proteinase/anti
      proteinase balance (cathepsins B and L, polynuclear neutrophil (PNN) elastase,
      alpha-1 proteinase inhibitor (alpha(1)PI) and its inhibitory capacity) in the rat
      respiratory tract. Thus, Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles
      produce oxidative stress conditions through not only iron-catalysed oxidative
      reactions but also inflammatory processes. However, B[A]P initiates only
      inflammatory responses. These pollutants generate increased levels of proteases
      and decrease the concentrations of free alpha(1)PI. There is also a clear
      relationship between the partial inactivation of alpha(1)PI and the occurrence of
      ROS after exposure to Fe(2)O(3), alone or as a carrier of B[A]P. Hence, the
      proteinase/anti-proteinase balance might be more disrupted by Fe(2)O(3) or B[A]P
      coated onto Fe(2)O(3) particles than by B[A]P alone. These results suggest a
      mechanism that can explain why B[A]P-coated onto Fe(2)O(3) particles are more
      injurious than B[A]P alone.

PMID- 10942903
TI  - Allometric respiration/body mass data for animals to be used for estimates of
      inhalation toxicity to young adult humans.
AB  - The relationship between body weight (BW) and respiratory minute volume (V(m))
      was reviewed by collecting a database from the literature. The data were
      separated into anaesthetized and non-anaesthetized groups. Only young adult
      terrestrial mammals were included in the final data set. This database is the
      largest to be reported to date, is the first to separate the anaesthetized and
      non-anaesthetized groups and is matched to the target population of young, fit
      adult humans. The data set of non-anaesthetized animals contained 142 studies
      representing 2616 animals and 18 species from mice at 12 g body weight to horses
      and a giraffe at ca. 500 kg body weight. Analysis of the data indicated a power
      law (allometric) relationship between the minute volume and body weight. The
      resulting allometric equations for the empirical relationship between minute
      volume and body weight are: log(10)V()(m)= -0.302 + 0.809 log(10)BW and V(m) =
      0.499 BW(0.809)where V(m) is the minute volume (l min(-1)) and BW is the body
      weight (kg). From these equations, a minute volume of 15.5 lmin(-1)was obtained
      for a 70 kg human in the same physiological and/or emotional state as the
      animals. The results of the analyses were compared to other empirical studies in
      the literature, the more recent of which also indicated a scaling factor of 0.8.
      The relationship between minute volume and body weight is recommended for use in
      estimating the inhalation toxicity to young adult humans (military personnel),
      because this is the first study to use a large database focused exclusively upon
      non-anaesthetized young adult terrestrial mammals.

PMID- 10942904
TI  - Two-generation reproduction and developmental neurotoxicity study with sodium
      chlorite in the rat.
AB  - The potential for sodium chlorite to produce reproductive toxicity, developmental
      neurotoxicity and alterations in hematology and thyroid hormones was evaluated in
      Sprague-Dawley rats administered sodium chlorite in the drinking water
      continuously for two generations. The F(0) generation animals (30 of each gender
      per group) and F(1) generation animals (25 of each gender per group) selected to
      rear the F(2) generation were allowed free access to drinking water containing 0,
      35, 70 or 300 ppm sodium chlorite for a 10-week prebreed period, through mating
      for males and through mating, gestation and lactation for females. These drinking
      water concentrations corresponded to sodium chlorite doses of approximately 4, 8
      and 30 mg kg(-1) day(-1) for males and 5, 10 and 39 mg kg(-1) day(-1) for
      females, respectively. Evaluations included standard reproductive and postnatal
      indices, sperm morphology and motility, estrous cyclicity, a functional
      observational battery, motor activity, auditory startle, swim maze, hematology,
      serum thyroid hormone analyses and histopathology of reproductive and nervous
      system tissues. Sodium chlorite resulted in a decrease in water consumption in
      all groups and a decrease in food consumption and body weights in the 70 and 300
      ppm groups. There was no evidence of reproductive toxicity. Pup body weight was
      decreased in the 300 ppm group and small delays were observed in the time to
      preputial separation and vaginal opening. Mild anemia and mild methemoglobinemia
      were observed for animals in the 300 ppm group. Thyroid hormone levels were not
      affected by treatment. Changes to the nervous system were limited to small
      decreases in amplitude of auditory startle response for postnatal day (PND) 25
      pups in the 70 and 300 ppm groups and a small decrease in absolute brain weight
      for PND 11 pups in the 300 ppm group. These effects were considered to be of
      questionable neurotoxicological significance. Based on the results of this study,
      the no-observed-effect level (NOEL) for effects on reproduction and thyroid
      hormones is 300 ppm. The no-observed-adverse-effect levels (NOAEL) for
      hematological toxicity and neurotoxicity are considered to be 70 and 300 ppm,
      respectively.

PMID- 10942905
TI  - Cytotoxicity of some potential DNA intercalators (carbazole, acridine and
      anthracene derivatives) evaluated through neutrophil chemiluminescence.
AB  - A modifying effect of potential DNA intercalators, belonging to a group of
      carbazole, acridine and anthracene derivatives, on the course of luminol
      dependent chemiluminescence of neutrophils (polymorphonuclear leucocytes; PMNL)
      in the process of phagocytosis was studied. This effect was also examined in
      reactive-oxygen-species-generating non-cellular reaction systems consisted of
      myeloperoxidase or xanthine oxidase. Adriamycin (Doxorubicin), which is widely
      applied to neoplasm therapy, was used as a reference intercalator in the
      conducted experiments. It was demonstrated that some structurally different
      derivatives of carbazole inhibited the light emission from N-formyl-methionyl
      leucyl-phenylalanine (fMLP)-induced neutrophils to the same degree as adriamycin.
      It can be suggested that the same inhibitory effect was caused by either a
      different cellular distribution of the derivatives or different interactions of
      the derivatives with reactive oxygen species in the investigated systems.
      Measurements of chemiluminescence suggested that the thiol group in one of the
      carbazole derivatives could strongly interfere with oxidative cell metabolism. In
      contrast to the analogous derivative of carbazole, both anthracene and acridine
      derivatives, possessing an N-1'-hydroxyethyl-ethylenodiamino group, induced
      different increases in chemiluminescence accompanying the process of neutrophil
      phagocytosis. Cytotoxicity of the investigated derivatives, being tested
      previously in cancer cells with a sulphorhodamine B assay, was found to possess a
      specific representation in the complex picture of the derivative-caused
      modification both of neutrophil and enzymatic non-cellular chemiluminescence. We
      suggest that chemiluminescence assays may serve as a helpful tool in the primary
      screening of drug cytotoxicity.

PMID- 10942906
TI  - Beryllium-induced toxicity and its prevention by treatment with chelating agents.
AB  - The efficacy of Tiron and calcium disodium EDTA in the treatment of experimental
      beryllium intoxication was investigated in rats. Beryllium nitrate was
      administered intramuscularly (50 mg kg(-1)) once only, provoking duration
      dependent changes. Maximum changes were recorded after a 7-day regimen.
      Considerable inhibition was recorded in protein and glycogen contents, as well as
      in the activity of alkaline phosphatase, glucose-6-phosphatase, acid phosphatase
      and lipid peroxidation. These parameters were restored considerably with
      chelation therapy, but comparatively Tiron offered better protection. These
      findings were further confirmed by atomic adsorption spectrophotometry. Tiron was
      found to be significantly more effective than CaNa(2)EDTA in reducing the
      beryllium concentration in the liver, kidney and lungs.

PMID- 10942907
TI  - Evaluation of subchronic (13-week) and reproductive toxicity potential of
      intravaginal gel-microemulsion formulation of a dual-function phenyl phosphate
      derivative of bromo-methoxy zidovudine (compound whi-07) in B(6)C(3)F(1) mice.
AB  - Heterosexual transmission of human immunodeficiency virus (HIV) accounts for 90%
      of all new infections worldwide and significantly contributes to new acquired
      immunodeficiency syndrome (AIDS) cases in the USA. In a systematic effort to
      develop a microbicidal contraceptive capable of preventing HIV transmission as
      well as providing fertility control, we previously identified novel phenyl
      phosphate derivatives of 3'-azido-3'-deoxythymidine (zidovudine) that exhibit
      potent anti-HIV and spermicidal activities. This study reports the preclinical
      studies of our lead compound WHI-07, 5-bromo-6-methoxy-5,6-dihydro-3'
      azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate, for use as a dual
      function topical microbicide. In vivo toxicity studies in non-human primates and
      rodents given WHI-07 (20 mg kg(-1)) intravenously and intraperitonealy,
      respectively, had no detectable adverse effects on hematological and clinical
      chemistry profiles. The 13-week subchronic and reproductive toxicity potential of
      an intravaginal gel-microemulsion formulation of WHI-07 was studied in mice to
      support its further development as a dual-function microbicide. Groups of ten
      female B(6)C(3)F(1) mice were exposed intravaginally to a gel-microemulsion
      formulation containing 0, 0.5, 1.0 or 2.0% WHI-07, 5 days a week, for 13
      consecutive weeks. On a molar basis, these concentrations represent 1400-5700
      times their in vitro spermicidal potency EC(50)) and 1.4 x 10(6)-5.7 x 10(6)
      times their in vitro anti-HIV activity(50)). After 13 weeks of intravaginal
      treatment, half of the treated mice were evaluated for toxicity and the other
      half were mated with untreated males to evaluate potential reproductive and
      developmental effects. The endpoints that were evaluated included survival, body
      weight gain, hematological and clinical chemistries, absolute and relative organ
      weights and histopathology. The WHI-07 applications did not cause weight loss,
      morbidity, mortality or specific tissue lesions detectable by histopathology.
      Repeated intravaginal exposure of mice to WHI-05 for 13 weeks had no adverse
      effects on subsequent reproductive performance (100% fertile), neonatal survival
      (>95%) or pup development. These findings collectively show that the experimental
      dual-function anti-HIV and contraceptive agent WHI-07 did not cause significant
      acute or subchronic toxicity.

PMID- 10942908
TI  - Interactive and delayed effects of pyridostigmine and physical stress on
      biochemical and histological changes in peripheral tissues of mice.
AB  - Gulf War veterans were taking pyridostigmine orally against possible exposure to
      nerve agents as well as being under physical stress. This study was designed to
      investigate the delayed effects of pyridostigmine and treadmill exercise on
      cholinesterase activity, lipid peroxidation and histology of peripheral tissues
      of mice. Male NIH Swiss mice were divided into four groups of 15 animals each and
      treated as follows: sedentary control; exercise training for 10 weeks;
      pyridostigmine (1.2 mg kg(-1), p.o.) for 2 weeks during weeks 5 and 6; and
      pyridostigmine plus exercise training. The mice were sacrificed 24 h after the
      last exercise, and blood, triceps muscle and sciatic nerve were isolated and
      analyzed. The group treated with pyridostigmine alone showed decreased plasma
      butyrylcholinesterase (BChE) activity (87% of control), whereas pyridostigmine
      plus exercise significantly decreased the BChE activity (79% of control),
      indicating an interactive effect of the combination. Acetylcholinesterase (AChE)
      activity did not alter significantly in red blood cells, platelets or sciatic
      nerve with either of the treatments. However, AChE activity in triceps muscle
      decreased significantly (78% of control) in the group treated with pyridostigmine
      plus exercise. Creatine phosphokinase activity in plasma increased slightly
      (compared to control, pyridostigmine or exercise group) in mice treated with
      pyridostigmine plus exercise, which may be indicative of perturbation in the
      integrity of the skeletal muscle due to combination. However, there were no
      obvious histological abnormalities in the triceps muscle detected between
      experimental and control groups. Interaction of pyridostigmine and exercise
      significantly increased the concentration of the end product of lipid
      peroxidation (malondialdehyde) (124% of control) in triceps muscle, indicating an
      oxidative stress response of the combination. These results indicate that
      physical stress enhanced the delayed toxic effects of a subchronic oral dose of
      pyridostigmine primarily in the skeletal muscle of mice.

PMID- 10942909
TI  - Epidermal cytokines in murine cutaneous irritant responses.
AB  - Investigations on cytokines in skin irritancy or non-immunological irritant
      contact dermatitis (ICD) should improve our understanding of their complex
      mechanism. Numerous studies showed, however, that similar epidermal cytokines
      have been detected in irritant and allergic reactions, suggesting a lack of
      specific cytokines that clearly differentiate allergic from irritant reactions
      even though the pathomechanisms between allergic contact dermatitis (ACD) and ICD
      are distinguished. Recent data, however, indicate that some mediators may be
      restricted to allergic responses (contact hypersensitivity). This could provide
      the impetus to study their implication on irritant reactions. We overview the
      epidermal cytokines involved in irritant responses compared to those in contact
      hypersensitivity based on published results of studies using in vitro cell
      cultured murine keratinocytes and in vivo murine models.

PMID- 10942910
TI  - Disordered eating among adolescents: associations with sexual/physical abuse and
      other familial/psychosocial factors.
AB  - OBJECTIVE: To examine associations between disordered eating behaviors and a
      range of familial/psychosocial factors, including sexual and physical abuse
      experiences, among adolescent girls and boys. METHOD: A statewide representative
      sample of 9,943 students in Grades 7, 9, and 11 in Connecticut completed a
      comprehensive survey on adolescent health within their schools. The present
      analysis focused on measures of disordered eating, sexual and physical abuse,
      familial factors, peer support, and depressive symptoms. RESULTS: Youth at
      increased risk for disordered eating included those who perceived family
      communication, parental caring, and parental expectations as low and those who
      reported sexual or physical abuse experiences. After adjusting for differences in
      familial/psychosocial factors, associations between abuse experiences and
      disordered eating were weakened. However, youth who reported sexual abuse were
      still at increased risk for disordered eating, even after adjusting for physical
      abuse, sociodemographics, and familial/psychosocial factors (girls: odds ratio
      [OR] = 1.99, 95% confidence interval [CI] = 1.51, 2.64; boys: OR = 4.88, 95% CI =
      2.94, 8.10). Youth reporting physical abuse were also at increased risk for
      disordered eating after adjusting for sexual abuse, sociodemographics, and
      familial/psychosocial factors (girls: OR = 2. 00, 95% CI = 1.52, 2.62; boys: OR =
      1.95, 95% CI = 1.26, 3.04). DISCUSSION: The findings suggest that strong familial
      relationships may decrease the risk for disordered eating among youth reporting
      abuse experiences, but both sexual and physical abuse are strong independent risk
      factors for disordered eating among both adolescent girls and boys.

PMID- 10942911
TI  - Which comes first in the pathogenesis of bulimia nervosa: dieting or bingeing?
AB  - OBJECTIVE: Clinical experience has indicated that dieting usually precedes the
      onset of binge eating in the development of bulimia nervosa (BN). However, data
      confirming this in nonclinical, representative samples are lacking. METHOD: Using
      results obtained from the National Women's Study (NWS), we were able to determine
      the chronological relationship between age of onset of significant dieting
      (attempting to lose 15 lbs) and onset of bingeing in 85 respondents who met DSM
      III-R criteria for BN. These respondents were a subset of over 3,000 female adult
      U.S. women who completed a random telephone interview (averaging 40 min and
      including screenings for rape, sexual molestation, aggravated assault,
      posttraumatic stress disorder [PTSD], and BN). RESULTS: We found that the age of
      first serious attempt to diet preceded the age of first binge in 46% of cases.
      There were no significant differences in histories of victimization experiences
      among the groups. First binge preceded first serious diet in 37% of cases, and
      these behaviors occurred during the same age in 17% of cases. DISCUSSION: These
      data confirm that dieting is more likely to precede binge eating, although binge
      eating precedes significant dieting in a substantial proportion of bulimic
      respondents.

PMID- 10942912
TI  - An epidemiological study of eating disorders in Iran.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of anorexia
      nervosa (AN) and bulimia nervosa (BN) as well as the prevalence of weight
      concerns and weight loss behaviors among schoolgirls in Tehran, Iran. METHOD: A
      two-stage approach was used. We screened a large sample of adolescent girls aged
      15-18 (n = 3, 100) with a Persian translation of the Eating Attitudes Test (EAT
      26). Girls who screened positively were further evaluated with the Eating
      Disorder Diagnostic Inventory and a supplementary clinical interview. RESULTS:
      Results showed a lifetime prevalence of 0.9% for AN, 3.2% for BN, and 6.6% for
      the partial syndrome. Body dissatisfaction and a desire to be thin were common in
      this population. DISCUSSION: This study suggests that the prevalence of eating
      disorders among female adolescents in Teheran is comparable to prevalence rates
      reported by studies in Western societies, and somewhat higher than what has been
      reported in other non-Western societies.

PMID- 10942913
TI  - Effects of acute food deprivation on eating behavior in eating disorders.
AB  - OBJECTIVE: Effects of acute food deprivation on eating behavior in bulimic
      patients and controls were investigated. It was predicted that food deprivation
      would increase overall food intake and result in overeating in bulimics. METHOD:
      Following 19 hr of food deprivation (in which breakfast and lunch were skipped),
      or no deprivation, food intake was measured in 9 inpatients with anorexia nervosa
      (binge eating/purging subtype, ANB), 10 inpatient (BN/in) and 9 outpatient
      (BN/out) normal-weight bulimics, and 11 unrestrained and 10 restrained controls.
      RESULTS: A general trend for increased food intake following deprivation was
      found. However, only BN/in patients consumed significantly more and selected
      higher energy foods following deprivation. ANB patients demonstrated the greatest
      degree of variability in intake and the least magnitude of change in ratings as a
      function of eating. DISCUSSION: A period of acute food deprivation did not
      trigger marked eating pathology as evidenced by overconsumption. Chronic dietary
      restraint may be a more potent precipitating factor in overeating than absolute
      number of hours of food restriction.

PMID- 10942914
TI  - Assessment of macronutrient and micronutrient intake in women with anorexia
      nervosa.
AB  - OBJECTIVE: The purpose of this study is to evaluate the accuracy of diet history
      compared to observed food intake in the nutritional assessment of women with
      anorexia nervosa (AN) and healthy age-matched controls. METHOD: One-month diet
      history was compared to 1-day observed food intake in 30 women with AN and 28
      control subjects. RESULTS: Reported intake by diet history was similar to
      observed intake for macronutrient composition and fat intake for patients with
      AN. Reported energy intake was higher than observed intake (1,602 +/- 200 kcal
      vs. 1,289 +/- 150 kcal, p <.05), but was in agreement with predicted energy
      expenditure by the Harris-Benedict equation (1,594 +/- 18 kcal, p =.97) in
      patients with AN. Micronutrient intake by diet history was highly correlated with
      observed intake in patients with AN. More than one half of the patients with AN
      failed to meet the recommended dietary allowance (RDA) for vitamin D, calcium,
      folate, vitamin B12, zinc, magnesium, and copper when assessed by diet history.
      In contrast to patients with AN, diet history did not correlate with observed
      intake of energy, macronutrients, or most micronutrients among the controls.
      DISCUSSION: Diet history is an accurate tool to assess fat intake and
      macronutrient composition in patients with AN and demonstrates significant
      micronutrient deficiencies in this population. The agreement between total energy
      intake and predicted energy expenditure supports the overall utility of the diet
      history in the nutritional assessment of patients with AN.

PMID- 10942915
TI  - Cytokine production in patients with anorexia nervosa, bulimia nervosa, and
      obesity.
AB  - OBJECTIVE: We previously reported elevated serum levels of the cytokines
      interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients
      with anorexia nervosa (AN). We investigated the cellular production of these two
      cytokines and of interferon-gamma (IFN-gamma), interleukin-1alpha (IL-1alpha),
      and tumor necrosis factor-alpha (TNF-alpha) in subjects with AN, bulimia nervosa
      (BN), and obesity as well as in normal-weight control subjects. METHODS:
      Supernatant fluids from isolated peripheral blood mononuclear cells (PBMC)
      incubated with and without concanavalin A (ConA) were assayed for cytokine
      concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant
      differences across the four groups were found in the stimulated cellular
      production of IFN-gamma and IL-6. Stimulated IFN-gamma production was elevated in
      the AN group compared to controls. IL-6 production was significantly elevated in
      obese subjects relative to the two normal-weight groups, BN and controls, and
      tended to be higher in the AN group than in the controls, but not significantly
      so. IL-1alpha production was greater in obese subjects. CONCLUSION: The findings
      of increased IFN-gamma production and a tendency toward increased IL-6 production
      (both of which suppress food intake in animals) in individuals who severely
      restrict food intake suggest a potential role for these cytokines in the
      pathogenesis of AN. Elevated IL-6 and IL-1alpha production by PBMC in obese
      individuals requires further investigation to determine if these cytokines
      contribute to the development or perpetuation of obesity.

PMID- 10942916
TI  - Criterion validity of the multiaxial assessment of eating disorders symptoms.
AB  - OBJECTIVE: The purpose of this investigation was to establish the criterion
      validity of the Multiaxial Assessment of Eating Disorders Symptoms (MAEDS). The
      MAEDS is a brief, comprehensive, self-report measure for the evaluation of eating
      disorders treatment outcome. It assesses six symptoms associated with eating
      disorders with subscales for binge eating, purgative behavior, avoidance of
      forbidden foods, restrictive eating, fear of fatness, and depression. METHOD: To
      establish criterion validity, we compared the subscale scores of the MAEDS across
      four eating disorder diagnoses, specified by subtype (bulimia nervosa, purging
      type; anorexia nervosa, binge-eating/purging type; anorexia nervosa, restricting
      type; and binge eating disorder). Participants who did not meet the full
      diagnostic criteria for an eating disorder, but who did meet criteria for a
      partial syndrome eating disorder, were grouped with the full eating disorder
      diagnostic subtypes. RESULTS: The criterion validity of the MAEDS was supported
      by the pattern of subscale scores for the different eating disorder diagnostic
      groups. Also, with few exceptions, persons diagnosed with anorexia nervosa,
      bulimia nervosa, and binge eating disorder, in comparison to subthreshold cases
      of anorexia nervosa, bulimia nervosa, and binge eating disorder, had equivalent
      scores on the subscales of the MAEDS. DISCUSSION: These findings support the
      criterion validity of the MAEDS and add to a growing literature that questions
      differences in severity of eating disorder symptoms in full syndrome versus
      partial syndrome cases.

PMID- 10942917
TI  - Test-retest reliability of the eating disorder examination.
AB  - OBJECTIVE: The purpose of this investigation was to determine the test-retest
      reliability of the Eating Disorder Examination (EDE). METHOD: This study examined
      the test-retest and interrater reliability of the EDE in 20 adult women with a
      range of eating disorder symptoms. Trained assessors administered the EDE to
      participants on two separate occasions, ranging from 2 to 7 days apart. RESULTS:
      Test-retest correlations were.7 or greater for all subscales and measures of
      eating disorder behaviors except for subjective bulimic episodes and subjective
      bulimic days. Interrater reliability was uniformly high with correlations
      above.9. DISCUSSION: Results provide further support for the reliability of the
      EDE, but suggest that smaller binge episodes may not be reliable indicators of
      eating pathology.

PMID- 10942918
TI  - Children into DSM don't go: a comparison of classification systems for eating
      disorders in childhood and early adolescence.
AB  - OBJECTIVE: To evaluate the reliability of diagnostic classification systems for
      eating disorders when applied to children and young adolescents. METHOD: Eighty
      one patients were randomly selected from a population of 226 children (age 7-16)
      presenting with eating difficulties to a specialist clinic. Diagnoses were
      assigned according to three classification systems: the 10th edition of the
      International Classification of Diseases (ICD 10), the 4th edition of the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and Great Ormond
      Street (GOS) criteria. Ratings were performed by two clinicians blind to the
      diagnosis of the other. RESULTS: Interrater reliability values (kappa) for the
      three systems were 0.357 (ICD 10), 0.636 (DSM-IV), and 0.879 (GOS). Using DSM
      criteria, more than 50% of children were classified as eating disorder not
      otherwise classified (EDNOS) or could not be classified. DISCUSSION: DSM-IV and
      ICD 10 criteria are of little value in the classification of the eating
      difficulties of children. The GOS criteria, which were developed for this age
      range, are more reliable. The classification of eating disorders in childhood
      needs reevaluation.

PMID- 10942919
TI  - Open treatment of overweight binge eaters with phentermine and fluoxetine as an
      adjunct to cognitive-behavioral therapy.
AB  - OBJECTIVE: This open clinical trial examined the efficacy of treating obese
      patients with binge eating disorder (BED) with phentermine and fluoxetine in the
      setting of cognitive-behavioral therapy (CBT). METHOD: Sixteen obese women
      received individual CBT along with phentermine/fluoxetine. Treatment goals
      included elimination of binge eating, weight loss, and reduced psychological
      distress. Following active treatment, patients were offered once-monthly
      maintenance treatment for 3 years. RESULTS: Patients showed significant reduction
      in binge frequency, weight loss, and psychological distress at the end of active
      treatment, but regained most of the weight within 1 year. At 18-month follow-up,
      there was an ongoing reduction in binge eating for patients who continued
      maintenance. DISCUSSION: Treatment produced comparable binge suppression and more
      weight loss than most reported studies of CBT alone. However, there is
      significant weight regain, particularly following medication discontinuation.
      This study does not support the long-term clinical utility of adding
      phentermine/fluoxetine to CBT for BED.

PMID- 10942920
TI  - Restraint, tendency toward overeating and ice cream consumption.
AB  - OBJECTIVE: The examination of the prediction of grams of ice cream eaten by
      preload, restraint, susceptibility toward overeating, and interaction terms.
      METHOD: A milkshake-ice cream study on 200 females using the Restraint Scale (RS)
      and the restraint and disinhibition scales from the Three-Factor Eating
      Questionnaire (TFEQ) and the Dutch Eating Behavior Questionnaire (DEBQ).
      Restraint and tendency toward disinhibition are treated as continuous variables
      in hierarchical step up multiple regression analyses. RESULTS: There was no
      disinhibition effect, as subjects did not overeat after the milkshake, neither in
      function of their restraint nor in function of their tendency toward overeating
      or any interactions between these. Tendency toward overeating was the most
      important variable for ice cream consumption. Restraint itself, the part that
      remained after tendency toward overeating had been partialed out, was not related
      to ice cream consumption. In terms of its association with ice cream consumption,
      the DEBQ disinhibition scale seems more promising than the TFEQ disinhibition
      scale. DISCUSSION: Restraint theory seems mainly valid for dieters with a
      tendency toward overeating. Tendency toward overeating may even be a better
      predictor than restraint, opening the possibility that overeating precedes
      dieting.

PMID- 10942921
TI  - Assessment of shape- and weight-based self-esteem in adolescents.
AB  - OBJECTIVES: The Adolescent version of the Shape and Weight-Based Self-Esteem
      (SAWBS-A) Inventory provides a contextual measure of the importance of shape and
      weight to overall feelings of self-worth. The psychometric properties of the
      adult SAWBS Inventory have been previously established. The present research
      examined the psychometric properties of this measure in adolescent females, and
      compared structural aspects of self-concept in symptomatic and nonsymptomatic
      individuals. METHOD: A school sample of 197 adolescents completed the SAWBS-A
      Inventory and measures to assess concurrent and discriminant validity. A
      subsample completed the SAWBS-A Inventory a second time, 1 week later. RESULTS:
      SAWBS-A scores were stable over 1 week and correlated with measures of eating
      disorder symptomatology. The scores also discriminated between adolescents
      reporting few or no disturbed eating symptoms and possible/probable cases.
      Comparison of self-esteem profiles in these two groups revealed that in addition
      to body, the groups differed in the extent to which facial appearance contributed
      to feelings of self-worth. CONCLUSIONS: The SAWBS-A Inventory may be useful in
      examining structural dimensions of self-esteem in adolescents.

PMID- 10942922
TI  - Geographic hematology: an evolving concept.

PMID- 10942923
TI  - Abnormal regulation of HFE mRNA expression does not contribute to primary iron
      overload.
AB  - BACKGROUND AND OBJECTIVES: Hereditary hemochromatosis (HHC) is a common,
      recessively inherited, genetic disorder associated with an abnormality of the HFE
      gene. Subjects homozygous for a point mutation in the gene coding sequence,
      leading to the amino acid substitution C282Y, are usually affected by the
      disease. A second point mutation, causing the amino acid substitution H63D, has
      been described, and compound heterozygotes for the two mutations or homozygotes
      for the H63D mutation are at risk of developing a milder form of HHC. In
      populations of northern European origin the C282Y substitution accounts for more
      than 90% of cases of HHC. In Italy, however, fewer than 70% of patients with HHC
      are homozygous or compound heterozygous for HFE mutations. Even in the absence of
      mutations in its coding region, the HFE gene might be involved in the
      pathogenesis of HHC through inhibition of transcription of the gene or reduced
      stability of its mRNA. DESIGN AND METHODS: Since little is known about the
      regulation of HFE expression, we investigated 17 subjects heterozygous for one of
      the HFE mutations and with biochemical evidence of iron overload and compared the
      levels of wild type and mutated mRNAs in their peripheral blood cells. c-DNA
      regions flanking the mutated codons were amplified by reverse transcriptase
      polymerase chain reaction (PCR). PCR products derived from the two alleles were
      differentiated and quantified by digestion with restriction enzymes,
      electrophoresis in an agarose gel stained with ethidium bromide and densitometric
      scanning of the gel. RESULTS: In all cases wild type and mutated mRNAs were
      expressed at similar levels, suggesting that reduced expression of an HFE allele
      coding a normal protein is not involved in the pathogenesis of iron overload.
      However, we can not rule out that a tissue specific regulation of HFE expression
      in the cells directly involved in iron absorption is altered and contributes to
      the pathogenesis of the disease. E INTERPRETATION AND CONCLUSIONS: Our results
      suggest that primary iron overload is a multigenic syndrome; this hypothesis is
      strongly supported by the recent demonstration that the juvenile hemochromatosis
      locus maps to human chromosome 1q.

PMID- 10942924
TI  - Report of the Spanish Gaucher's disease registry: clinical and genetic
      characteristics.
AB  - BACKGROUND AND OBJECTIVES: Since 1993 the demographic, clinical, analytical,
      genetic and follow-up data of Spanish patients with Gaucher's disease (GD) have
      been collected in an anonymous national database. Some statistical analyses of
      these data are reported concerning the distribution, clinical and genetic
      characteristics of GD in Spain and the response to enzyme replacement therapy
      (ERT) is evaluated. DESIGN AND METHODS: We performed a cohort study in Spanish GD
      patients by national inquiry, submitted by mail to 75 Spanish hospitals (over 300
      beds) directed to internal medicine, hematology and pediatric departments. The
      questionnaire included 30 questions (gender, height, weight, date of birth, date
      of diagnosis, abode and number of relatives affected, bone crises, neurologic
      symptoms, other symptoms, liver and spleen size, hemoglobin, leukocyte and
      platelet count, tartrate resistant acid phosphatase, ALT/AST, chitotrioxidase
      activity, total plasma cholesterol, triglycerides, high density lipoprotein
      cholesterol, enzymatic activity of acid -glycosides, mutation, X-ray examination,
      magnetic resonance imaging-MRI-evaluation, spleen removal, and orthopedic
      procedures (ERT, date of first infusion). Each case with a presumed diagnosis was
      considered an enrolled patient. Written informed consent was obtained from all
      patients. The cases without enzymatic or genetic diagnosis were studied in a
      reference laboratory (the same for all the samples). Clinical status was
      evaluated by Zimran's severity score index. The enzymatic activity of acid 
      glycosides was determined in cellular extracts of peripheral blood granulocytes
      by a fluorescent method using an artificial substrate (4-methyl-umbelliferyl -D
      glycoside). Polymerase chain reaction (PCR) molecular analysis was performed in
      DNA samples to characterize the mutations (N370S, L444P, IVS2+1, 84GG, D409H,
      R463C and G377S) of the glycoside genes. Two groups were created according to age
      at diagnosis: children under 15 years and adults, in order to evaluate clinical,
      genetics and follow-up. Effectiveness of ERT was evaluated using objective
      parameters (hemoglobin, platelets, liver and spleen size, skeletal lesions),
      before and after therapy. In patients under ERT, quality of life (QOL) was
      assessed by a SF-36 modified inquiry, including 22 questions. Statistical
      analysis including descriptive and frequency distribution for each variable was
      performed, the ANOVA test was used to identify differences between groups. Paired
      t-tests (before and during therapy) were carried out. The degree of linear
      association among measured variables was estimated by Pearson's correlation.
      RESULTS: By December 1999 one hundred and fifty-five patients from 117 families
      had been included from 66 Spanish Hospitals; the inquiry was complete for 114
      patients. Mean age at diagnosis: 24.0+/-16.9 years, M/F: 72/83. No symptoms were
      present at diagnosis in 19.3%; visceral disease was present in 95.6% and bone
      disease in 62.4%. Hemoglobin levels, leukocyte and platelet counts were below the
      normal range in 62.3% of cases. Higher acid phosphatase levels were observed in
      99% of cases; biochemical liver dysfunction tests were found in 42.9%. The test
      for acid glycosidase showed a marked decrease in enzymatic activity. Morphologic
      documentation (spleen or liver tissue, bone marrow biopsy or aspirate) of GD was
      obtained in 71% of the patients. The most frequent mutations observed were N370S
      (46.3% of the alleles detected), and L444P (18.5%). In 18.7% of the cases the
      disease was stable or progressing slightly; in 23.8% the spleen had been removed
      between 1-14 years after diagnosis and 60.6% were under ERT. Children showed both
      greater liver enlargement and higher SSI (p = 0.0001). There was a correlation
      between SSI and clinical or analytical data in adults patients for spleen size
      (Z: 3.142; CI: 0. 173-0.637; p= 0.0017). In 35 patients on ERT, clinical and
      analytic data improved as did self-evaluated QOL (p< 0.0001). (A

PMID- 10942925
TI  - Angiogenic factors in multiple myeloma: higher levels in bone marrow than in
      peripheral blood.
AB  - BACKGROUND AND OBJECTIVES: To study the role of some soluble factors in the
      process of angiogenesis that accompanies multiple myeloma (MM). DESIGN AND
      METHODS: The concentrations of three well-known angiogenic peptides, vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and
      hepatocyte growth factor (HGF) were evaluated by an ELISA method. All of these
      factors were measured in the plasma obtained from peripheral blood (PB) and bone
      marrow (BM) aspirates of 34 patients affected by plasma cell disorders. This
      series included one patient with a solitary extramedullary plasmacytoma, 17
      patients with MM at diagnosis, and 16 with previously treated MM. RESULTS: In all
      the patients, the concentration of each angiogenic factor was higher in bone
      marrow than in peripheral blood. Mean values of the three angiogenic factors in
      BM or in PB were lower in stage I than stage II-III. One patient with
      extramedullary solitary myeloma had high levels of VEGF and bFGF but this
      increase was not found in the other 6 patients with extramedullary disease when
      compared with patients without extramedullary disease. VEGF and bFGF did not
      correlate with each other while HGF showed a weak correlation with VEGF and a
      stronger one with bFGF. Moreover, VEGF correlated with features of disease
      activity, such as C-reactive protein, and 2-microglobulin, while both bFGF and
      HGF showed an inverse correlation with albumin level. No correlation was found
      between VEGF, bFGF and HGF levels and age, M protein level, osteolytic lesions,
      or percentage of BM plasma cells. Since angiogenic factors may be released by
      normal cells in response to hypoxia, we also evaluated erythropoietin (EPO)
      levels (which correlate with the hypoxic stimulus) both in PB and BM plasma of
      these patients but none of the measured angiogenic factors correlated with EPO
      levels. Interpretation and Conclusions. Several soluble factors may play a role
      in the angiogenic activity described in MM but their contribution to the
      progression of disease may be different. The finding of higher levels of these
      factors in BM than in PB might indicate that the bone marrow environment is their
      major source. Concentrations of angiogenic factors parallel the activity of
      disease and are independent of the hypoxic stimulus.

PMID- 10942927
TI  - Etoposide, mitoxantrone and prednisone: a salvage regimen with low toxicity for
      refractory or relapsed non-Hodgkin's lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Relapsed non-Hodgkin's lymphoma (NHL) is preferably
      treated with high-dose therapy and stem cell support. However, not all patients
      qualify for intensive chemotherapy. We evaluated the efficacy and toxicity of a
      new salvage chemotherapy regimen designed for patients with relapsed or
      refractory NHL who are not appropriate candidates for high-dose therapy (HDT).
      DESIGN AND METHODS: Seventy-nine patients received a regimen consisting of
      etoposide (350 mg/m(2) i.v. day 1), mitoxantrone (14 mg/m(2) i.v. day 1) and
      prednisone (80 mg/m(2) p.o. days 1-5) (EMP). The majority had aggressive NHL.
      Twenty-one patients were elderly, i.e. >60 years of age; RESULTS: The overall
      response rate in the 79 patients was 38% as compared to 67% in the elderly. The
      progression-free survival was 54% and 30% at 12 months and 24 months,
      respectively. The toxicity of the regimen was relatively low. No toxic deaths
      have occurred. In 28 of 231 cycles (12%) a CTC-grade 2-4 infection was
      encountered. Twenty-one hospital admissions were necessary because of infection
      or fever. Other toxicity was rare. Toxicity was not greater in the elderly
      patients. WHO performance status 2-4 and elevated serum lactate dehydrogenase
      (LDH) concentrationv were adverse prognostic factors for response as well as for
      overall survival. Another adverse prognostic factor for response was age <60
      years. INTERPRETATION AND CONCLUSIONS: EMP is a new salvage regimen with a
      relatively low toxicity. It should be considered for patients with relapsed or
      refractory NHL who are not candidates for standard reinduction therapy and stem
      cell transplantation.

PMID- 10942926
TI  - Calcium antagonists potentiate P-glycoprotein-independent anticancer drugs in
      chronic lymphocytic leukemia cells in vitro.
AB  - BACKGROUND AND OBJECTIVES: A major obstacle to the successful use of chemotherapy
      in the treatment of leukemia and other cancers is the emergence of drug
      resistance. One of the most studied resistance mechanisms is mediated by P
      glycoprotein, which can be modulated by calcium channel blockers. Here we
      investigated whether the Ca(2+) channel blockers verapamil and nifedipine are
      toxic alone and in combination with P-glycoprotein-independent anticancer drugs
      against chronic lymphocytic leukemia (CLL) cells in vitro. DESIGN AND METHODS:
      Verapamil cytotoxicity was investigated in peripheral blood samples of 35
      patients with B-cell CLL and 10 healthy control subjects. Cytotoxicity was
      assessed in in vitro 4-day cultures using 14C-leucine incorporation as an
      indicator of cell viability. Interactions were tested with Ca2+ channel blockers
      and cyclosporine or 7 anticancer drugs: (i) chlorambucil, (ii) 2
      chlorodeoxyadenosine, (iii) cisplatin, (iv) fludarabine, (v) prednisolone, (vi)
      adriamycin, and (vii) vincristine. The mode of cell death was assessed by annexin
      binding and DNA ladder formation. RESULTS: Verapamil induced dose- and time 
      dependent death of CLL cells in vitro. A statistically significant effect (p =
      0.0085) was noted with as little as 4 microM verapamil. The mode of cell death
      was apoptotic as determined by annexin positivity and condensation of verapamil
      treated cells. Verapamil effectively potentiated the toxicity of cyclosporine and
      all the anticancer drugs mentioned above. Furthermore, nifedipine, a more
      specific L-type calcium channel antagonist, significantly potentiated the effect
      of chlorambucil against CLL cells. Interpretation and Conclusions. Calcium
      channel blockers enhance the effect of P-glycoprotein-independent anticancer
      drugs remarkably. This indicates that the death signals initiated by calcium
      depletion and anticancer drugs together facilitate cell death. This novel finding
      opens a new avenue to modulate, by using calcium channel antagonists, the effect
      of traditional anticancer drugs having different mechanisms of P-glycoprotein
      independent action.

PMID- 10942928
TI  - Amifostine, a reactive oxigen species scavenger with radiation- and chemo
      protective properties, inhibits in vitro platelet activation induced by ADP,
      collagen or PAF.
AB  - BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) generation has been
      suggested to represent an important regulatory mechanism of platelet reactivity
      in both physiologic and pathologic conditions; consistent with this hypothesis is
      the observation that free-radical scavengers may inhibit platelet activation,
      thus contributing to the regulation of their reactivity. The purpose of the
      present study is to study the in vitro effects of amifostine (WR-2721, ethyol ),
      a selective cytoprotective agent for normal tissues against the toxicities of
      chemotherapy and radiation, on platelet activation induced by the physiologic
      agonists ADP, collagen and PAF. DESIGN AND METHODS: The effect of amifostine,
      added to the experimental system at final concentrations ranging from 10(-7) M to
      10(-5) M, was studied on platelet aggregation induced by the following
      physiologic agonists at the given concentrations: ADP (1 microM), collagen (2
      microg/mL), and PAF (0.1 microg/mL). Platelet aggregation was investigated using
      a platelet ionized calcium aggregometer and was expressed as the percentage
      change in light transmission. Furthermore, thromboxane B((2)) (TxB((2))) levels
      and nitric oxide (NO) production were determined by radioimmunoassay and by
      evaluating the total nitrite/nitrate concentration using a commercially available
      colorimetric kit, respectively, both in the control system and after the addition
      of amifostine. RESULTS: Amifostine inhibited both platelet aggregation and
      TxB((2)) production induced by ADP, collagen and PAF, in a dose-dependent manner.
      Amifostine proved to be an effective inhibitor of platelet function and the
      effect was more pronounced if platelets were stimulated with ADP, intermediate
      when collagen was the chosen agonist, and less evident, though present, when PAF
      was used. Platelets stimulated with ADP, collagen or PAF produced significant
      amounts of NO over the baseline. When amifostine was added at a final
      concentration of 5 microM, it significantly increased ADP, collagen and PAF
      induced NO production, which suggests that NO release by activated platelets was
      involved in the inhibitory effect of amifostine. INTERPRETATION AND CONCLUSIONS:
      Amifostine proved to be an effective inhibitor of platelet activation induced in
      vitro by physiologic inducers. This previously unrecognized effect was more
      evident with the weak agonist ADP and was related to reduced NO consumption by
      free radicals generated during platelet activation. Amifostine proved to be not
      only a powerful cytoprotectant, but, more generally, a therapeutic agent endowed
      with several relevant, though largely unknown, biological effects. Finally, our
      data once again support the concept that oxidative balance is of crucial
      importance in regulating platelet reactivity in both health and disease.

PMID- 10942929
TI  - Assessment of patient capability to self-adjust oral anticoagulant dose: a
      multicenter study on home use of portable prothrombin time monitor (COAGUCHECK).
AB  - BACKGROUND AND OBJECTIVES: Self-testing and self-monitoring with portable
      prothrombin time (PT) monitors has been shown to be feasible and safe. However
      the ability of patients on chronic oral anticoagulant therapy (OAT) to self
      adjust their dose without specific training has never been properly evaluated.
      The aims of this study were to evaluate: 1) the ability of patients on chronic
      OAT to self-adjust their dose without specific training; 2) the integration of a
      portable PT monitor (Coagucheck, Roche Diagnostics, Germany) for home use into
      routine patient care in anticoagulation clinics. DESIGN AND METHODS: A nested
      case-control study was conducted in four centers of the Italian Federation of
      Anticoagulation Clinics (FCSA). Patients (n=78) on stable OAT for at least 6
      months (cases: 47 men, 31 women, age range: 18-75 years) were enrolled on a
      volunteer basis after passing an Abbreviated Mental Test and providing informed
      consent. After three instruction sessions on the use of Coaguchek, subjects
      performed the PT test at home, communicated the INR results to the Center and
      suggested the dose adjustment and date for next control as they thought
      appropriate. However, they were requested to follow the prescription made by the
      Center. Controls (78 subjects) matched by age (+/- 5 years), sex and therapeutic
      range with the cases, were selected from among those who attended the
      anticoagulation clinics and managed by usual care. RESULTS: When compared with
      the dose prescribed by the Clinic, the dose suggested by warfarin and
      acenocoumarol users was equal to or within +/- 6% of the mean weekly dose in 80%
      and 82% of suggestions, respectively. Time spent in the therapeutic range during
      the study was the same (80%) for cases and controls. INTERPRETATION AND
      CONCLUSIONS: Selected patients on chronic anticoagulant therapy can acquire a
      satisfactory ability for self-adjustment of OAT dose without specific training.

PMID- 10942930
TI  - Immune reconstitution after autologous hematopoietic stem cell transplantation in
      relation to underlying disease, type of high-dose therapy and infectious
      complications.
AB  - BACKGROUND AND OBJECTIVES: Autologous peripheral stem cell transplantation
      (APSCT) is increasingly used for various hematologic malignancies and solid
      tumors. The objective of this study was to analyze the immune reconstitution
      after APSCT and see if there was any correlation with diagnosis, age, type of
      high-dose therapy, CD34(+) selection of the autograft and double vs single APSCT.
      DESIGN AND METHODS: Lymphocyte subset recovery was studied in 46 consecutive
      patients with hematologic malignancies and breast cancer, who underwent APSCT.
      Eleven patients with multiple myeloma received tandem autografts. Thirty-one
      patients were given total body irradiation (TBI) as part of the high-dose
      treatment. Eighteen patients received a CD34(+) selected graft. The percentage
      and absolute numbers of lymphocyte populations, T-cells (CD2(+), CD3(+)), B-cells
      (CD19(+)), NK cells (CD56(+ )CD3(-) and CD16(+)CD3(-)) and T-cell subpopulations
      (CD4(+), CD8(+), CD4(+)CD45RA(+), CD4(+ )CD45RO(+), CD4(+)DR(+), CD8(+
      )CD45RO(+), CD8(+)DR(+)), were monitored with flow cytometry during the first
      year after APSCT. RESULTS: The total B-cell (CD19(+)) and T-cell (CD3(+)) counts
      were reconstituted to normal levels 2-4 months after APSCT. All patients had a
      low CD4/CD8 ratio during the observation period, related to both a low number of
      CD4(+) cells and elevated numbers of CD8(+) cells. The low number of CD4(+) cells
      was due to a persistently low level of naive CD4(+)CD45RA(+) cells. A high
      proportion of the CD8+ cells displayed a phenotype compatible with activated T
      cells (CD8(+)DR(+)) up to 10 months after autografting. The number of NK cells
      (CD56(+)3(-) or CD16(+)3(-)) reached normal values within one month post
      transplant. No single variable, such as diagnoses, age, TBI as part of the high
      dose treatment, tandem autografting or CD34(+) selection of the graft, influenced
      the immune or hematopoietic reconstitution and no correlation with documented
      infectious complications was found. INTERPRETATION AND CONCLUSIONS: Despite
      heterogeneity of diseases, age, initial treatment and high-dose regimens,
      lymphocyte subset analysis did not reveal any differences in hematopoietic or
      immune reconstitution. All patients had a low CD4(+)/CD8(+) ratio during at least
      the first year post-transplant, caused by a persistent increase of CD8(+)
      lymphocytes and a constant reduction of CD4(+) lymphocytes, making the patients
      susceptible to infections for a prolonged period of time post-transplant.

PMID- 10942931
TI  - Allogeneic transplantation of G-CSF mobilized peripheral blood stem cells from
      unrelated donors: a retrospective analysis.
AB  - BACKGROUND AND OBJECTIVES: Allogeneic peripheral blood stem cell transplantation
      (PBSCT) from matched siblings has lead to clinical results comparable to those of
      standard bone marrow transplantation (BMT). We report the outcome of 79 patients
      transplanted with PBSC from unrelated donors. DESIGN AND METHODS: In 61 cases
      PBSC were used for primary transplantation whereas 18 patients were treated for
      relapse or graft-failure. In 35 patients receiving primary transplants, T-cell
      depletion (TCD) using CD34 positive selection of PBSC with or without additional
      T-cell depletion had been performed to reduce the risk of graft-versus-host
      disease (GvHD). RESULTS: The rate of primary graft-failure was higher (20%) in
      the TCD group than in that receiving unmanipulated grafts (UM) (5%, p=0.007).
      Patients with standard risk (n=34) receiving first transplants had a
      significantly better overall (60.4% vs. 24%, p=0.02) and disease-free survival
      (57.2% vs. 22.3%, p=0.006) compared to a high risk group of patients (n=21).
      There were no differences in the speed of neutrophil and platelet engraftment
      between TCD and UM transplants. As expected, the cumulative risk for acute GvHD
      grade II.-IV was significantly higher in the patients who had received UM grafts
      (71.8% vs. 38.1%, p=0.005). Although a trend towards a better survival rate was
      observed after TCD transplantation (52.2%) compared to the UM group (38.1%), this
      difference was not statistically significant. The probability of relapse was
      significantly higher in patients after UM transplants (38.8% vs. 8. 4%). This
      apparent paradox is explained by the higher number of high-risk patients in this
      group (p=0.03). Multivariable analysis of disease-free survival revealed risk
      category (p=0.02) and use of ATG (p=0.03) to be of significant impact. All
      patients (n=6) with non-malignant diseases are alive with full donor chimerism.
      INTERPRETATION AND CONCLUSIONS: These data show that PBSC from unrelated donors
      can be transplanted either unmanipulated or CD34 selected. Prospective studies
      comparing BMT with PBSCT from unrelated donors are needed in defined disease
      categories.

PMID- 10942932
TI  - Follow-up of chimerism status after allogeneic HLA-mismatched stem cell
      transplantation by detection of non-shared HLA alleles.
AB  - BACKGROUND AND OBJECTIVES: Chimerism studies after allogeneic transplantation are
      usually performed using cytogenetic analysis, PCR-VNTR or PCR-STR. Here, we
      report an alternative method for following the chimerism status after an HLA
      mismatched stem cell transplantation (SCT), detecting the presence of non-shared
      HLA alleles by reference-strand mediated conformation analysis (RSCA). DESIGN AND
      METHODS: We tested this new approach on allogeneic related haploidentical SCT,
      unrelated cord blood transplantation, and HLA-mismatched unrelated donor SCT. The
      quantification of the chimerism was performed by laser detection of fluorescent
      labeled primers on an automated DNA sequencer. RESULTS: In all cases this
      technique was able to detect mixed chimeras. The technique detected above 5% of
      residual cells when the analysis was based on HLA-class I and above 3% for HLA
      class II. This sensitivity is similar to that of the PCR-VNTR analysis.
      INTERPRETATION AND CONCLUSIONS: This method avoids the need to search for an
      informative locus (which is essential for PCR-VNTR or -STR). Moreover, we did not
      find the phenomenon of preferential amplification that is observed with most
      VNTR, thus avoiding the need for construction of standard curves to quantify
      mixed chimeras. We conclude that the detection of the non-shared HLA alleles by
      RSCA is a useful approach for chimerism follow-up after HLA-mismatched SCT.

PMID- 10942933
TI  - The lung as a target organ in patients with hematologic disorders.
AB  - The lung is one of the organs most severely affected by complications during the
      course of hematologic disorders. In the last years an impressive amount of
      progress has been made in clarifying the pathogenesis of lung diseases,
      particularly those occurring in conditions of severe immunosuppression such as
      bone marrow transplantion, acquired immunodeficiency syndrome or leukemia.
      Peculiar anatomical characteristics render the lung parenchyma highly susceptible
      to infections, but the clinical outcome is due not only to the injury induced by
      the pathogens but also to their interactions with inflammatory cells and
      particularly to the effects of a wide network of secreted cytokines.
      Polymorphonuclear cells, macrophages, lymphocytes and structural pulmonary cells
      (epithelial cells, interstitial cells) generate a variety of cytokines and growth
      factors which, in turn, may be responsible for the majority of the clinical
      effects in response to infections, such as those of Pneumocystis carinii and
      cytomegalovirus, but also to certain drugs or to radiation. The pathogenesis of
      graft-versus-host disease (GVHD) is still poorly understood, but animal models
      seem to demonstrate the involvement of a number of cytokines and growth factors,
      together with toxic effects induced by conditioning regimens.

PMID- 10942935
TI  - Sweet's syndrome and myelodysplasia: two entities with a common pathogenetic
      mechanism? A case report.

PMID- 10942934
TI  - Juvenile hemochromatosis associated with B-thalassemia treated by phlebotomy and
      recombinant human erythropoietin.
AB  - Juvenile hemochromatosis is a rare genetic disorder that causes iron overload.
      Clinical complications, which include liver cirrhosis, heart failure,
      hypogonadotropic hypogonadism and diabetes, appear earlier and are more severe
      than in HFE-related hemochromatosis. This disorder, therefore, requires an
      aggressive therapeutic approach to achieve iron depletion. We report here the
      case of a young Italian female with juvenile hemochromatosis who was unable to
      tolerate frequent phlebotomy because of coexistent ss-thalassemia trait. The
      patient was successfully iron-depleted by combining phlebotomy with recombinant
      human erythropoietin.

PMID- 10942936
TI  - Cutaneous flagellate pigmentation by bleomycin.

PMID- 10942937
TI  - Bone marrow aspiration from the posterior iliac crest and spine using a sterile
      and pyrogen free disposable spinal needle (Yale spinal 18 Gx31/2") without local
      anesthetic.

PMID- 10942938
TI  - Diagnosis of iron deficiency in patients infected with human immunodeficiency
      virus.

PMID- 10942940
TI  - Cytoplasmic overexpression of p53 and p21(ras) in megaloblastic anemia.

PMID- 10942939
TI  - Screening for iron overload and HFE mutations in a university hospital.

PMID- 10942941
TI  - Acute monocytic leukemia in the adult presenting with associated extramedullary
      gastric infiltration and ascites.

PMID- 10942942
TI  - Molecular and clinical prognostic factors in BFM-treated childhood acute
      lymphoblastic leukemia patients: a single institution series.

PMID- 10942943
TI  - Chronic lymphocytic leukemia and Hodgkin's disease. Clinicopathologic study of
      three cases with good prognosis.

PMID- 10942944
TI  - CD3(-) large granular lymphocyte leukemia with clonal rearrangement of the gamma
      and beta genes of the T-cell receptor.

PMID- 10942946
TI  - Role of endosonography in rectal lymphoma.

PMID- 10942945
TI  - Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia
      type T-cell lymphoma by combined methotrexate and prednisone.

PMID- 10942947
TI  - Hepatitis C virus infection and new association with extrahepatic disease:
      multiple myeloma.

PMID- 10942948
TI  - Kaposi's sarcoma after allogeneic bone marrow transplantation in a child.

PMID- 10942949
TI  - Platelet cryopreservation using second-messenger effector and low-dose (2%)
      dimethyl sulfoxide. In vitro evaluation of post-thawing platelet activity with
      the platelet function analyzer.

PMID- 10942950
TI  - Anti-D immunoglobulin in children with newly diagnosed immune thrombocytopenic
      purpura: a pilot study.

PMID- 10942951
TI  - Treatment of refractory ITP with extracorporeal immunoadsorption over a protein-A
      sepharose column: a report of two cases.

PMID- 10942952
TI  - Programmed versus non-programmed freezing of umbilical cord blood.

PMID- 10942953
TI  - Identification of one novel and three other point mutations in the protein C gene
      of five unrelated brazilian patients with hereditary protein C deficiency.

PMID- 10942954
TI  - Oral anticoagulants and cyclosporin A.

PMID- 10942955
TI  - Fatal visceral varicella-zoster infection following rituximab and chemotherapy
      treatment in a patient with follicular lymphoma.

PMID- 10942956
TI  - Cyclosporine treatment of acquired hemophilia due to factor VIII antibodies.

PMID- 10942957
TI  - Bridging the gap with ORF ESTs.

PMID- 10942958
TI  - Large-scale screening on small scale.

PMID- 10942959
TI  - New biopharmaceuticals in the USA: trends in development and marketing approvals
      1995-1999.
AB  - The Tufts Center for the Study of Drug Development has collected data on the
      clinical and approval phases of the 26 new biopharmaceuticals approved by the US
      Food and Drug Administration between 1980 and 1999. Here, the data for
      biopharmaceuticals approved between 1995 and 1999 are presented grouped by
      product category, review status, orphan-drug designation and therapeutic
      indication, and the mean phase lengths are compared. They are also compared with
      the data for approvals during the periods 1982-1989, 1990-1994 and 1996-1998.

PMID- 10942960
TI  - Synthesis of hierarchical materials.
AB  - A major goal of material science is to produce hierarchical materials that are
      ordered on all length scales, from the molecular (1-100 A) via the nano (10-100
      nm) to the meso (1-100 microm). In these materials, the larger-scale properties
      can be controlled by choosing molecular characteristics. Methods developed to
      produce three-dimensional, bulk-like hierarchical structures include biomimetic
      methods, which use polypeptides as building blocks, and amphiphile and colloidal
      templating, which use amphiphilic or colloidal mesophases as templates for
      inorganic mesoporous materials. Designing finite mesostructures with a given
      geometry still remains a challenge.

PMID- 10942961
TI  - Synthetic spider silk: a modular fiber.
AB  - Spiders make their webs and perform a wide range of tasks with up to seven
      different types of silk fiber. These different fibers allow a comparison of
      structure with function, because each silk has distinct mechanical properties and
      is composed of peptide modules that confer those properties. By using genetic
      engineering to mix the modules in specific proportions, proteins with defined
      strength and elasticity can be designed, which have many potential medical and
      engineering uses.

PMID- 10942962
TI  - Downstream processing of plasmid DNA for gene therapy and DNA vaccine
      applications.
AB  - Interest in producing large quantities of supercoiled plasmid DNA has recently
      increased as a result of the rapid evolution of gene therapy and DNA vaccines.
      Owing to the commercial interest in these approaches, the development of
      production and purification strategies for gene-therapy vectors has been
      performed in pharmaceutical companies within a confidential environment.
      Consequently, the information on large-scale plasmid purification is scarce and
      usually not available to the scientific community. This article reviews
      downstream operations for the large-scale purification of plasmid DNA, describing
      their principles and the strategy used to attain a final product that meets
      specifications.

PMID- 10942963
TI  - The development of optical nanosensors for biological measurements.
AB  - This article discusses and documents the basic concepts of, and developments in,
      the field of optical nanosensors and nanobiosensors. It describes the progression
      of this field of research from its birth up to the present, with emphasis on the
      techniques of sensor construction and their application to biological systems.
      After a brief overview of the techniques for fabricating nanometer-sized optical
      fibers, we describe the various types of transducer and bioreceptor molecule
      presently used for nanosensor and nanobiosensor fabrication.

PMID- 10942964
TI  - Mitochondrial gene therapy: an arena for the biomedical use of inteins.
AB  - Mitochondrial DNA (mtDNA) mutations underlie many rare diseases and might also
      contribute to human ageing. Gene therapy is a tempting future possibility for
      intervening in mitochondriopathies. Expression of the 13 mtDNA-encoded proteins
      from nuclear transgenes (allotopic expression) might be the most effective gene
      therapy strategy. Its only confirmed difficulty is the extreme hydrophobicity of
      these proteins, which prevents their import into mitochondria from the cytosol.
      Inteins (self-splicing 'protein introns') might offer a solution to this problem:
      their insertion into such transgenes could greatly reduce the encoded proteins'
      hydrophobicity, enabling import, with post-import excision restoring the natural
      amino acid sequence.

PMID- 10942965
TI  - Journal of Pharmacy & Pharmaceutical Sciences: a medium of scientific
      communication for the 21st century.

PMID- 10942966
TI  - Bioequivalence and interchangeability of narrow therapeutic range drugs. Canadian
      Society for Pharmaceutical Sciences discussion.

PMID- 10942967
TI  - Racemic drugs: racemic mixture, racemic compound, or pseudoracemate?

PMID- 10942968
TI  - The calcium channel blocker controversy - a caution to physicians and pharmacist.

PMID- 10942969
TI  - Buccal mucosa as a route for systemic drug delivery: a review.
AB  - Within the oral mucosal cavity, the buccal region offers an attractive route of
      administration for systemic drug delivery. The mucosa has a rich blood supply and
      it is relatively permeable. It is the objective of this article to review buccal
      drug delivery by discussing the structure and environment of the oral mucosa and
      the experimental methods used in assessing buccal drug permeation/absorption.
      Buccal dosage forms will also be reviewed with an emphasis on bioadhesive
      polymeric based delivery systems

PMID- 10942970
TI  - A simple and efficient method for radiolabeling of preformed liposomes.
AB  - A simple and efficient method for radiolabeling preformed liposomes was developed
      using hepatobiliary imaging agent (99m)Tc-diisopropyl iminodiacetic acid ((99m)Tc
      DISIDA). Chloroform extraction of (99m)Tc-DISIDA from aqueous solutions results
      in 80% radioactivity in the organic phase due to its lipophilic properties.
      However, with the presence of reduced glutathione (gamma-Glu-Cys-Gly), chloroform
      extraction results in only 30% of label in the organic phase because the (99m)Tc
      DISIDA complex undergoes reduction decomposition to more hydrophilic species by
      reaction with glutathione. The incorporation efficiency of the (99m)Tc-DISIDA
      into the liposomes containing reduced glutathione was greater than 90%. The
      labeled liposomes were stable up to 24 h in saline and 90% FBS after preparation.
      Biodistribution studies in mice showed that (99m)Tc labeled liposomes accumulated
      in liver and spleen at 24 h postinjection, unlike (99m)Tc-DISIDA. Compared to
      hexamethylpropyleneamine oxime (HMPAO), the (99m)Tc-DISIDA compound is much
      cheaper and has a longer shelf life when used for liposome labeling. The labeling
      technique described here could be used for monitoring pharmacokinetic and
      pharmacodynamic changes of liposomes, and tumor or infection imaging when coupled
      with targeting antibodies.

PMID- 10942971
TI  - Isolation and pharmacological characterization of microsomal human liver
      flumazenil carboxylesterase.
AB  - PURPOSE: In vivo the biotransformation of the imidazobenzodiazepine antagonist
      flumazenil leads to the formation of two metabolites, flumazenil acid and N
      demethylated flumazenil. In the present study we investigated the role of
      carboxylesterases for the metabolism of flumazenil. METHODS: We purified a non
      specific carboxylesterase (EC 3.1.1.1) from human liver microsomes that catalyzes
      the hydrolysis of flumazenil to flumazenil acid and, in presence of methanol the
      formation of flumazenil methyl ester an in vivo unknown metabolite. The
      purification procedure included solubilization of the microsomes obtained from
      human livers with Triton X-100 and subsequent chromatography of the 100,000 x g
      supernatant on blue-sepharose, DEAE-sepharose, hydroxyapatite and final
      chromatofocusing. RESULTS: The purified esterase isozyme exhibited an apparent
      subunit molecular weight of 59 kDa as estimated by SDS gelelectrophoresis, a
      native molecular weight of 170 kDa determined by a calibrated gel filtration
      column suggesting that the active enzyme is a trimer. The isoelectric point of
      the enzyme was approximately 5.4. The specific activities of the purified enzyme
      were 5.8 nmol/(min*mg protein) protein for the formation of flumazenil acid and
      31 nmol/(min*mg protein) for the synthesis of the flumazenil methylester. The
      purified enzyme obeys simple Michaelis-Menten kinetics with K(M) values of 665
      microM for flumazenil acid, 1011 mM for methanol and 900 microM for the
      flumazenil methylester. PMSF, a specific inhibitor for serine proteases and
      mammalian acetylcholinesterase, completely inhibited the formation of flumazenil 
      acid and the flumazenil methylester at a concentration of 100 microM. No
      synthesis of the flumazenil -methylester could be observed by incubation of the
      purified esterase with flumazenil acid in the presence of methanol leading to the
      conclusion that the enzymatically catalyzed reaction is a transesterification.
      The purified esterase was digested with endoproteinase LysC. A 15 amino acid long
      peptide was isolated and showed identical matches to carboxylesterase cDNAs from
      human liver and lung. CONCLUSION: Our results show that carboxylesterase isozymes
      play an important role in the detoxification and metabolism of flumazenil.
      Because of enzymatic, catalytic and structural properties a similarity of the
      characterized flumazenil carboxylesterase with human liver cocaine
      carboxylesterase is possible.

PMID- 10942972
TI  - [Should fibromyalgia survive the century?].

PMID- 10942973
TI  - [Do hematopoietic growth factors have a role in the treatment of drug-induced
      agranulocytosis?].
AB  - PURPOSE: Our study was aimed at determining the role of hematopoietic growth
      factor in drug-induced agranulocytosis. METHODS: Fifty-five cases of drug-induced
      agranulocytosis were reviewed and subdivided retrospectively into a G-CSF group
      (n = 15) and an untreated group (n = 40). Mortality and hematological recovery
      (number of days required for neutrophil counts to exceed 1.5 x 10(9)/L) were
      studied in the two groups. RESULTS: The mean granulocyte count was 0.09 x
      10(9)/L. All patients presented infection. In the G-CSF group, no mortality (0%
      versus 5%, P = 0.85) and a shorter recovery time (8.1 versus 9.5 days P = 0.39)
      were observed. No significant difference between the two groups was observed in
      either the duration of antibiotic therapy (9.3 days in the G-CSF group versus
      10.1 days in the untreated group, P = 0.51) or duration of hospitalization (10
      days in the treated group versus 11 days in the G-CSF group, P = 0.46).
      CONCLUSION: Our results as well as a literature review indicate that G-CSF could
      decrease the time to hematological recovery and perhaps reduce mortality.
      However, the exact role of hematopoietic growth factors requires further
      investigations.

PMID- 10942974
TI  - [Hematologic and immunologic manifestations of primary cytomegalovirus infections
      in non-immunocompromised hospitalized adults].
AB  - PURPOSE: Cytomegalovirus (CMV) infection in non-immunocompromised adults can
      sometimes induce hematological and immunological disorders that may mislead
      diagnosis. METHODS: Case reports of hospitalized non-immunocompromised adults
      with positive serology for CMV including the presence of immunoglobulin M or
      seroconversion were assessed in a retrospective study (1981-1998). We focused on
      clinical and biological abnormalities showing the role of CMV in disruption of
      functioning of hematological and immunological systems. RESULTS: Among 115
      patients, lymphoma-like syndrome with large adenopathies and/or splenomegaly was
      diagnosed in eight patients, uncovering underlying CMV infection. Lymphoma was
      accompanied by hematoma in two patients. Three patients presented leg purpura
      (with thrombotic thrombocytopenic purpura in one case), one patient had cutaneous
      vasculitis and on other a Still's disease. Blood abnormalities were mononucleosis
      (64%), anemia (20%), and thrombopenia (25%) often of peripheral or hemolytic
      origin or due to hypersplenia. Electrophoresis of serum proteins showed an
      increase in immune globulins in 56% of the cases and monoclonal abnormality in
      nine cases. Immunological assessment was conducted in 18 patients. At least one
      abnormality was depicted in ten patients, consisting of either antinuclear, anti
      platelet or anti smooth muscle antibodies, cryoglobulinemia, rheumatoid factor,
      or reduced complement fixation. CONCLUSION: Testing for CMV infection can be of
      value in case of blood or immunological disorders associated with clinical or
      biological signs. Although hematological disorders occur early, they are rarely
      severe. Immunological disorders are rarely symptomatic, but often raise issues
      regarding the potential genesis of immune diseases in at-risk patients.

PMID- 10942975
TI  - [IGM hyperimmunoglobulinemia anti-phosphatidylethanolamine antibodies of the IgM
      isotype: clinical and biological study of 72 patients with immune disorders].
AB  - PURPOSE: Antiphosphatidylethanolamine antibodies (aPE) are zwitterionic
      antiphospholipid antibodies that have been recently described in antiphospholipid
      syndrome. IgM is the most frequently observed isotype. We assessed the potential
      relationship between serum IgM levels and their presence. METHODS: Seventy-two
      patients (66 females, 6 males) positive for aPE of the IgM isotype were followed
      up for 2 years. They suffered from either an autoimmune disease or had clinical
      signs suggesting the existence of antiphospholipid syndrome or other immune
      disorders. Seventy-two control patients (58 females, 14 males) of similar age,
      with other immune disorders were also included in the study. For each of them,
      the IgM level was obtained and hyper-immunoglobulinemia M (hyper-IgM) was defined
      as a value upper than 2.5 g/L. Search for aPE of the IgM isotype was made using
      an in-house Elisa test. RESULTS: Half of the aPE-positive patients had serum
      hyper-IgM, whereas none of the aPE-negative patients had hyper-IgM. All IgMs were
      polyclonal. There was a positive correlation (r = 0.57, P = 0.001) between the
      level of IgM and the optical densities obtained by Elisa. The presence of a hyper
      IgM did not modify the clinical manifestations (arterial and venous thromboses,
      recurrent fetal losses), nor the positivity of lupus anticoagulant,
      anticardiolipin and anti-beta-2-glycoprotein 1 antibodies. CONCLUSION: The
      positive correlation between the IgM level and aPE level is of value, as it
      suggests a possible relationship between lymphocytic activation and auto
      antibodies production, which does not concern only aPE. Further studies regarding
      the antigenic specificity of IgM will probably provide further insights on IgM
      and phospholipid interactions.

PMID- 10942976
TI  - [Erythrocyte adhesion to vascular endothelium: clinical applications].
AB  - INTRODUCTION: The objectives of this paper are to review the environmental
      factors, the different erythrocyte ligands and the corresponding endothelial
      receptors involved in adhesion. CURRENT KNOWLEDGE AND KEY POINTS: Leukocyte
      adhesion to vascular endothelium is related to inflammation and has been widely
      studied. The adhesion of erythrocytes to vascular endothelium has been
      investigated more recently, mainly in the physiopathology of three diseases:
      diabetes mellitus, sickle cell disease and malaria. The three diseases are
      characterized by microvascular complications and are deleterious for the red
      blood cell membrane. They lead to abnormal erythrocyte adhesion to vascular
      endothelium. Thus better understanding of the mechanisms involved in red blood
      cell adhesion to the endothelium is important since it might lead to the
      development of new therapeutic targets. Progress in this field might contribute
      to therapeutic improvement in sickle cell disease and to the development of an
      antimalarial vaccine. FUTURE PROSPECTS AND PROJECTS: However, additional studies
      focusing on in vivo endothelium heterogeneity, the different subpopulations of
      red blood cells and the diversity of Plasmodium falciparum strains are required.
      The consequences of such erythrocytes/endothelium interactions on the endothelial
      functions remain to be established.

PMID- 10942977
TI  - [Falls, frailty and osteoporosis in the elderly: a public health problem].
AB  - INTRODUCTION: Elderly people can be subdivided into three groups: healthy elderly
      persons (65-70% of the population), elderly subjects with diseases (about 5%) and
      frail old people. Frailty represents "age-related physiologic vulnerability
      resulting from impaired homeotasic stock and a reduced capacity of the organism
      to withstand stress". It could lead elderly subjects to pathological, barely
      reversible, ageing. CURRENT KNOWLEDGE AND KEY POINTS: One of the main objective
      of geriatricians is to develop useful screening tools to identify people at high
      risk, thus allowing them to benefit from preventive interventions as early as
      possible. It has been suggested that the decline in homeostatic stock involves
      numerous physiological systems. Those at the core of frailty would be
      neuromuscular changes resulting in sarcopenia, neuroendocrine dysregulation, and
      immune disorders. A recent study has shown that increased levels of interleukin 6
      is a risk factor for frailty. FUTURE PROSPECTS AND PROJECTS: Work in progress
      aimed at identification of at-risk patients should: lead to early detection; draw
      attention on underestimated fields such as the nutritional status, sarcopenia, or
      gait disorders; promote the development of the standardized gerontological
      evaluation in order to identify the different components of frailty; and promote
      the development of non-pharmacological programmes including physical training,
      nutritional managing, and optimal social life.

PMID- 10942978
TI  - [Clinical trials in the elderly: ethical and methodologic considerations].
AB  - INTRODUCTION: Based on a literature review, main ethical and methodological
      issues raised by the implementation of randomized clinical trials involving
      elderly patients are discussed. CURRENT KNOWLEDGE AND KEY POINTS: Despite their
      rapidly growing number and the subsequent significant increase in consumption of
      health care services and its cost, elderly patients have seldom been involved in
      clinical trials. FUTURE PROSPECTS AND PROJECTS: However, the need for accurate
      scientific information on which relevant therapeutic decisions regarding this
      vulnerable population may be based has introduced marked changes in attitudes
      towards either clinical trials conducted in the elderly or requirements of
      various licensing authorities in regard to assessment of new drugs in elderly
      patients. Although difficulties pertaining to controlled clinical trials
      involving elderly patients may hamper both planning and carrying out of studies,
      completion of such trials may be achieved.

PMID- 10942979
TI  - [Multiple medullary and extramedullary plasmacytomas in an HIV infected female
      patient].
AB  - INTRODUCTION: Before the HIV infection era, plasmocyte tumor rarely occurred in
      patients younger than 40 years of age. Less frequent than lymphomas, the
      incidence of these blood diseases has however substantially increased in HIV
      infected patients. In these patients, in addition to onset at earlier age, their
      clinical presentation is quite different and extramedullary plasmocytomas in
      unexpected locations are more common. EXEGESIS: We report the case of a 29-year
      old HIV-infected female patient in whom were diagnosed occipital, parotidal,
      sphenoidal, epidural, and uterine plasmocytomas for which chemotherapy and
      subsequent radiotherapy were successful. The increase in the incidence of
      plasmocyte tumors in HIV-infected patients might be facilitated by Epstein Barr
      Virus (EBV) co-infection, HIV-related chronic antigenic stimulation, and
      secretion of interleukin 6 by infected lymphocytes. CONCLUSION: Plasmocyte tumors
      belong to neoplasia whose incidence is increased in HIV infection. Their
      currently poor diagnosis should be improved by highly active antiretroviral
      therapies allowing enhanced chemotherapy with possibility of autograft.

PMID- 10942980
TI  - [Splenic vascular occlusion in the course of pancreatic cancer].
AB  - INTRODUCTION: Pancreatic cancer is responsible for 6,000 deaths per year in
      France. During the course of the disease, venous thrombosis is common.
      Conversely, arterial thrombosis is rarely described. EXEGESIS: We report the case
      of a 59-year-old patient with pancreatic adenocarcinoma. Treatment by gemcitabine
      allowed rapid and persistent improvement of the body weight and a prolonged
      survival (18 months). Sudden complication, i.e. splenic arterial thrombosis,
      reversed the favorable outcome. CONCLUSION: Splenic venous thrombosis is a
      frequent complication occurring in the course of pancreatic cancer. It is easily
      diagnosed using abdominal computerized tomography. Arterial thrombosis is rarely
      observed. It might be due to either sporadic, unexpected, occurrence of cases
      related to the evolution of underlying pathological mechanisms, or to omitted
      treatment of vascular complications, as until the introduction of new anticancer
      drugs this disease was considered to be of very poor prognosis.

PMID- 10942981
TI  - [Thyrotoxic periodic paralysis: two new cases in Blacks].
AB  - INTRODUCTION: Thyreotoxic hypokalemic periodic paralysis (THPP) has mainly been
      described in Asian people. It is rare in Caucasians, and only 12 cases were
      reported in Blacks. EXEGESIS: We report two cases of THPP in black patients.
      Hypokalemia was important in case number 1, leading to severe flaccid tetraplegia
      with respiratory and cardiac complications, but was only mild in case number 2.
      Complete relief of paralysis was observed under potassic treatment in the first
      case and spontaneously in the second one. Hyperthyroidism was established only on
      the basis of biological tests in case number 1, and had been previously diagnosed
      but undertreated in case number 2. CONCLUSION: Whatever the patient's race, acute
      paralysis with hypokalemia requires testing for hyperthyroidism, even in the
      absence of suggestive clinical signs.

PMID- 10942982
TI  - [An irresistible weight gain].

PMID- 10942983
TI  - [A painful abdominal syndrome].

PMID- 10942984
TI  - [Superior vena cava syndrome revealing rhabdomyosarcoma in an adult].

PMID- 10942985
TI  - [Spontaneous paroxysmal hypothermia. Discussion of a case of a high level
      athlete].

PMID- 10942986
TI  - [Agranulocytosis connected with the taking of mianserin: a complication to be
      feared in the aged].

PMID- 10942987
TI  - Respiratory system inertance: investigation in a physical inertance model.
AB  - For analysis of respiratory system mechanics the very complex structure of the
      respiratory system is strongly simplified to a simple resistance-compliance
      model. While for most patients this simplification seems sufficient, in patients
      with pulmonary disease this model is inappropriate. Additionally, to regional
      inhomogeneity throughout the lung, large volume accelerations due to the strongly
      decreased respiratory system compliance together with a mass increase of the
      patients' lungs, i.e. an increased respiratory system inertance Irs, result in a
      significant inertive pressure contribution. The aim of this study was to develop
      a physical inertance model, and its description by conventional methods of
      respiratory monitoring. Its parameters are adjustable within the physiological
      range, with Irs between 0.06 and 0.2 mbar.s2.l-1. The model proved well with
      static and dynamic analysis of respiratory system parameters. Using our physical
      model it is possible to evaluate new methods of respiratory monitoring and to
      investigate experimentally the interrelationship of respiratory system
      parameters.

PMID- 10942988
TI  - Mechanical modeling of soft biological tissues for application in virtual reality
      based laparoscopy simulators.
AB  - For application in a Virtual Reality (VR) based laparoscopic surgery simulator,
      computationally efficient algorithms for the description of the mechanical
      behavior of soft tissue have been developed. The explicit Finite Element Method
      has turned out to be a robust method for this purpose provided that absolute
      strain formulations are applied. Furthermore, a VR model of a uterus and its
      adnexe has been generated and simulation results are presented.

PMID- 10942989
TI  - Telemedicine of the future: teleneuropathology.
AB  - The chief relevance of telemedicine lies in its capability to link medical
      practitioners and remote hospitals to larger or specialized facilities in a very
      fast electronic manner. This may become even more important due to current
      increase in subspecialization and demand for more precise diagnosis and
      consultation in difficult cases. A network attaching small clinics or
      laboratories to larger and more specialized units, and to highly specialized
      referral centers may improve the professional standard of health care services
      and education. For a wider use, a technological standardization will be required,
      since the existence of several types of computer and numerous image manipulation
      programs, have resulted in a proliferation of file formats. However, every
      potential user or client of telemedicine should keep in mind, that
      standardization also includes legal and ethical issues such as patient
      confidentiality and malpractice avoidance. The adoption of workable guidelines
      and protocols is required. Telepathology in general and teleneuropathology in
      particular is the practice of pathology at a distance, viewing digitized images
      of histological slides on a video monitor rather than directly through a light
      microscope. For the transmission of the digitized images from a telemicroscope to
      the remote diagnostic video monitor, different technologies such as ordinary
      telephone lines, broadband telecommunications channels, and the Internet can be
      used. The transmitted images may serve for primary neuropathological diagnosis,
      teleconsultation, quality assurance, proficiency testing, and distance learning.
      Static-imaging and dynamic-imaging are the two major competing technologies of
      telemicroscopy. Static-imaging systems appear to have levels of diagnostic
      accuracy which are not satisfactory for diagnostic neuropathology. On the
      contrary, high levels of diagnostic accuracy can be achieved using dynamic
      imaging systems with the transmission of live video images in real time and by
      using a robotized telemicroscope with the possibility to examine the entire
      histological specimen under control of the remote teleneuropathologist.

PMID- 10942990
TI  - PACS and multimodality in medical imaging.
AB  - A PACS (Picture Archiving and Communication System) is a system that is able to
      store, exchange, display and manipulate images and associated diagnoses from any
      modality within a hospital in a timely and cost-effective way. Several
      developments, such as the DICOM standard, fast and convenient networking, and new
      storage solutions for large amounts of data, make the setup of such a PACS system
      possible. As the information acquired with various imaging modalities is then
      available and often complementary, it is desirable for the clinician to have a
      point-by-point spatial co-registration of images from different modalities in
      order to enable a synergistic use of the multimodality imaging of a patient for
      increased diagnostic accuracy. Various types of algorithms are available for the
      matching of medical images from the same or from different modalities. Co
      registration algorithms based on voxel properties consist of a similarity or
      dissimilarity measure and an iterative or non-iterative method minimizing the
      dissimilarity or maximizing the similarity between the two images by a
      transformation of one image relative to the other.

PMID- 10942991
TI  - Simulation of human gait using computed torque control.
AB  - This paper presents a method for the mathematical modeling of both the single and
      double support phases of the human gait. The governing equations are obtained by
      considering the linkage model to be in a floating state and the foot-ground
      interaction is imposed in the form of geometric constraints. Two stages for the
      single support phase and one stage for the double support phase are considered,
      each described by a different foot-ground constraint. Feedback controller
      functioning according to the computed torque control method is used to achieve
      the normal gait described by the hip and ankle trajectories. Weighted least
      square optimization is used to solve the redundancy of control torques during the
      double support phase. The geometric simulation indicates that the imposed
      trajectories can be realized by the proposed model with some deviations in joint
      motions. The control strategy is tested by artificially perturbing the
      trajectories. The corrective actions are able to resume the desired pattern
      within half cycle, but with control torque magnitudes considerably away from
      reasonable limits. This is attributed to the insufficiency of the planar
      kinematic model and the assumption that the joint torques are unbounded.

PMID- 10942992
TI  - The effect of stem geometry on stresses within the distal cement mantle in total
      hip replacement.
AB  - Cement-stem debonding is one of the most common reasons for failure in Total Hip
      Replacement (THR). Four similar THR prostheses design configurations were
      investigated with reference to the influence of mechanical stress occurring in a
      cement mantle of differing thicknesses and potentially affecting clinical
      performance. Non-linear finite element analysis was performed on constant cement
      mantle thicknesses of 1, 2, and 4 millimetres. The results obtained indicate
      stress levels within the cement mantle decrease with increasing cement mantle
      thickness. The prosthesis distal tip is shown to have particular significance.
      Truncation of the distal tip hemisphere to a flat profile for the fixation of a
      centralizer increases the cement stresses.

PMID- 10942994
TI  - [Strategy of the law "About Food" in the Byelorussian Republic].

PMID- 10942993
TI  - Circumcision in paediatric surgery using an ultrasound dissection scalpel.
AB  - In contrast to electrocautery, the ultrasound dissection scalpel allows tissue
      dissection and haemostasis to be performed without the danger of thermal tissue
      damage or burning caused by uncontrolled active current. In a clinical
      application study performed on 24 boys with an average age of six years, we
      examined whether the use of this instrument is also practical in a routine
      operation such as circumcision. It was possible to perform all operations with
      the ultrasound dissection scalpel (Ultracision, manufactured by Ethicon) by the
      classic technique without the additional use of electrocautery for haemostasis.
      Although dissecting speed is slower than with conventional instruments, the fact
      that simultaneous haemostasis is possible meant that operations could be carried
      out quickly and with minimal bleeding. There were no perioperative complications
      such as haemorrhaging or burning. All children were examined postoperatively over
      an average of 3 weeks (range 1-8 weeks). Wound healing was completely without
      complications for 22 patients (92%). One patient (4%) suffered a candidal
      infection in the first postoperative week. One further patient (4%), who was
      already suffering preoperatively from an extended chronic inflammation of the
      prepuce, developed pronounced swelling postoperatively. Heavy scarring occurred
      subsequently in both cases. Our results show that the advantages of the
      ultrasound dissection scalpel, e.g. gentle tissue dissection with simultaneous
      haemostasis, can also be used to advantage for a technically simple operation
      such as circumcision without having to fear the risks of electrocautery.

PMID- 10942995
TI  - [The new methodic approach to the study of nutrition of pregnant women].
AB  - The author offers a modern technique of study of a nutrition of the pregnant
      women. It is based on use of a questionnaire-polling method, including the data
      of obstetrical anamnesis and basic characteristics of a social and economic
      status. The developed questionnaire, which contains seven sections, including
      data connected with the social and economic status, with moving activity of the
      women, with the values of consumption of the basic food substances, mode of a
      feed, pernicious habits, body weight of a pregnant woman.

PMID- 10942996
TI  - [Effects of lipids obtained from the liver of marine animals on the immunologic
      status and hematologic indices of rats].
AB  - The influence of lipids received from liver of king crab (Paralithodes
      camtschatica) and liver of pollack on some indices of immunologic status of an
      organism and hematologic indices in rats was studied. The animals were divided
      into three groups in dependence from kind of lipid in diet: the control group
      received in the composition of lipid component of diet--lard and sunflower oil in
      the ratio 1:1, the second group--lard and lipid from pollack liver (1:1), the
      third group--lard and lipid from crabs liver (1:1). The differences of rations
      concerned their lipid component. The content of triglycerides in a liver of
      pollack compounded--73%, in a liver of crabs--50%, the content of phospholipids
      in a liver of pollack--12%, in a liver of crabs it is much more--20%; the total
      sun of omega-3 acids in the experimental group is practically identical: 23.8 and
      23.1% accordingly. Some simulate influence of lipid from liver of crabs on the
      quantity of antibody forming cells of a spleen was noted. The tendency to
      decreasing of indices of humoral immunity was founded in rats, which received
      diet with lipid from liver of pollack. The decrease of the quantity of
      lymphocytes and the increase of the quantity of eosinophilic leukocytes in a
      peripheral blood of animals this group was noted in comparison with control and
      other experimental groups.

PMID- 10942997
TI  - [A specialized product with antioxidant action in the treatment of lipid
      disorders in experimental hyperlipoproteinemia].
AB  - At an experimental model of alimentary hyperlipoproteinemia the medical effect of
      specialized product "Zolotoi Rog", a composition of biologically active
      substances, antioxidants and honey, isolated from marine organisms, was analysed.
      The hypolipidemic effect of this product was defined at violations of lipid
      metabolism of blood and liver of animals. Deterioration of the processes of
      lipids peroxidation and raising activity of antioxidant system of an organism,
      were revealed.

PMID- 10942999
TI  - [Use of dietary fiber in experimental hepatitis in rats].
AB  - Hepatitis is most widespread form of a lesion of a liver taking an essential
      place among the causes of invalidity of the population. In present work the
      created food fibres allocated from various vegetative raw material are described.
      Is shown the food fibres of bean crops and secondary resources of processing of a
      grapes improve a general condition of laboratory animals with a liver struck by
      hepatitis.

PMID- 10942998
TI  - [Effects of infant formula feeding on the distribution of copper in the body of 8
      day-old rats].
AB  - The oxidase activity of ceruloplasmin (Cp, EC 1.16.3.1), the content of
      immunoreactive Cp and copper ion concentration were measured in the serum of
      eight day-old rats receiving either breast feeding (control group) or commercial
      nutritive mixture which has been recommended for the newborn children beginning
      from zero age (experimental group). It was shown that the artificial feeding
      caused almost 3-fold increase of Cp oxidase activity and copper content in the
      serum when compared to age-matched controls. No changes in the copper content per
      Cp molecule were observed. Dot-hybridization of the total liver polyribosomal RNA
      with Cp [32P]cDNA showed that the increased Cp level in the blood of the rats of
      experimental group correlated well with the level of expression of Cp gene. The
      copper content in the liver of experimental rats was two times lower that in
      control animals while no differences was found in the brain copper content
      between two groups of rats. The role of the regulation of Cp gene expression in
      the lactating mammary gland and of milk Cp in the copper homeostasis in the
      newborn body is discussed.

PMID- 10943001
TI  - [Effects of biologically active food additives with different contents of
      vitamins on the vitamin status in humans].
AB  - The comparative study of influence of two biologically active food additives with
      the different contents of vitamins is carried out: a drink "Zolotoi Shar", the
      dose of vitamins in which makes 50-90% from recommended daily consumption, and
      "Vitabalance 2000", the contents of vitamins in which at 2-17 of time exceeds
      need of organism. The use of both additives within 3 weeks resulted in increase
      of levels of vitamins C, A, E, B2, B6 and carotenoids in blood serum. However if
      in case of consumption of a drink an authentic level was reached only for vitamin
      C and beta-carotene, in a case "Vitabalance 2000" for all investigated vitamins
      except vitamin A. Thus, if the consumption of a drink has lowered frequency of
      deficiency of 3-4 vitamins, but has not allowed to liquidate it completely, in
      case of "Vitabalance 2000" consumption the simultaneous deficiency 3-4 vitamins.
      The received data allow to believe the biologically active food additives
      containing vitamins in amounts exceeding recommended consumption, are convenient
      for fast liquidation of hypovitaminoses, and the preparations containing vitamins
      in doses making 30-50% from need of organism, are acceptable for daily filling of
      insufficient consumption of vitamins with a usual diet for a long time.

PMID- 10943000
TI  - [Effectiveness of dietary non-starch polysaccharides in experimental toxic
      hepatitis].
AB  - The efficiency of some polysaccharides was investigated in mice with an
      experimental toxic hepatitis. Hepatitis was induced by the oral administration of
      10% solution CCl4 in olive oil at a dosage of 3 ml/kg body weight every day
      during 7 days. After that tested substances were administrated every day 30-40
      min before a feeding at a dosage of 150 mg/kg body weight during 14-21 days.
      Results showed that a calcium alginate, two low-methoxyl pectins (one with the
      degree of esterification about 50% and other with the degree of esterification
      less 5%), fucoidan, and chitozan, but not lambda-carrageenan and kappa
      carrageenan, have beneficial affects on liver total lipid, glycogen,
      malondialdehyde, and diene conjugates as well as on blood total lipid and alanine
      aminotransferase activity in animals with experimental toxic hepatitis.

PMID- 10943002
TI  - [Special features of actual nutrition and nutritional status of children living
      in the Yamal-Nenets Autonomous District].
AB  - Actual nutrition of children living at boarding-school of the Yamal-Nenets
      autonomous district and also characteristics of their health, such as capacity
      for work, vitamin metabolism, physical development and activity of bio-oxidant
      systems of organism have been studied. The obtained results have become the basis
      for developing scientifically substantiated principles of creating balanced
      nutrition ration with antioxidant properties for the children living at the Far
      North.

PMID- 10943003
TI  - [Use of a specialized soft drink based on plant raw material in nutrition of
      patients with diabetes mellitus].
AB  - The using of the low calorie soft drink "Forest gift" based on plant raw and
      enriched with vitamin C and iodine by patients with diabetes mellitus has
      resulted in the improvement of carbohydrates metabolism, provision of iodine and
      vitamin C and oxidant status of organism. Obtained data has promised to recommend
      this product for using in patient's ration.

PMID- 10943004
TI  - [Predicting effectiveness of omega-3 polyunsaturated fatty acid dietary treatment
      of patients with ischemic heart disease].
AB  - The possibility of using some erythrocyte fatty acids relations describing their
      metabolic interconversion for predicting efficiency of the omega-3
      polyunsaturated fatty acid diet has been justified. This method can be used to
      judge the individual sensitivity of patients with ischemic heart disease to diet
      treatment.

PMID- 10943005
TI  - [Clinical-metabolic evaluation of the effectiveness of the olive oil use in
      patients with cardiovascular diseases].
AB  - Investigation of influence of diet with olive oil on clinical, metabolic and
      immune indices in patients with ischemic heart disease and hypertension was
      conducted. As a result of the diet modified by the lipid component positive
      effect on the course of the diseases and lipid spectrum of blood, pronounced
      action on some indices of cell immunity, intensity of processes of lipid
      peroxidation were observed.

PMID- 10943006
TI  - [Biologically active food supplements in comprehensive therapy of patients with
      ischemic heart disease and hypertension and the background of overweight].
AB  - The influence of anti-atherosclerotic diet with including some biologically
      active additives, with contain vitamins C, E, beta-carotene, Zn, Cr, Se was
      studied in 80 patients with ischemic heart disease, hypertension disease. The
      usage of biologically active additives during 4 weeks has promoted positive
      changes of clinical symptoms of diseases against a background of lowering of
      serum cholesterol, triglycerides and increasing of IgA, IgG, vitamins A, E, C.

PMID- 10943007
TI  - [Effects of omega-3 polyunsaturated fatty acids of vegetable and animal origin on
      clinical and metabolic indicators and the intensity of lipid peroxidation in
      patients with ischemic heart disease and impaired carbohydrate tolerance].
AB  - Use fish and vegetable PUFA omega-3 from "Eicolen" in diet of patients with
      ischemic heart disease and ischemic heart disease complicated by impaired glucose
      tolerance resulted in positive dynamic of clinical manifestation, blood lipids
      and coagulograms of the patients, and did not influence significantly on lipid
      peroxidation.

PMID- 10943008
TI  - [Effects of mixture of fermented whey SGOL-1-40 ("Sgidolac") and sterilized milk
      on the course of experimental tuberculosis].
AB  - The effect of enzymolic whey SGOL 1-40 ("Sgidolac") and sterilized milk mixture
      on experimental tuberculosis process with mice has been investigated. The mice of
      CBA line infected with tuberculosis (Type H37Rv) and been given this mixture
      (rate SGOL 1-40 to milk 1:5) per os immediately after the infection at the amount
      of 0.5 g/Kg body weight per day every day, perished on 42-nd day, meanwhile the
      mice that had received the mixture 3 weeks before the infection and all the
      period after it, died on 46-th day he mice in the control group (infected and
      untreated) died on the 38-th day. The positive treatment and prophylactic effect
      of the SGOL 1-40 and milk mixture on the tuberculosis process has been stated and
      morphologically proved.

PMID- 10943009
TI  - [Experimental animal study of the safety of biologically active food supplement
      obtained from ginseng root].
AB  - The aim of present study was an investigations of safety of product "Bioton-1"
      which is suggested as biologically active food additive. Long-term intake the
      product "Bioton-1" by the rats Wistar during 6 month at doses of 0.75 ml per kg
      of body weight hadn't an unfavorable effects on integral, biochemical,
      hemotologic and morphologic parameters of animals. It was shown on two
      generations of rats that "Bioton-1" hadn't an embryotoxic, gonadotoxic and
      teratogenic effects and also hadn't negative effect on growth and development of
      posterity of rats. Including into the diet of rats product "Bioton-1" at dose of
      0.25 per kg of body weight during the whole life hadn't an effect on animals life
      duration.

PMID- 10943010
TI  - [Dietetic canned food using ocean fish and plant components].
AB  - The results of the creating canned ground goods of a new kind are described in
      this article. The main character references of food value of hake and the canned
      ground foods based on it. It has been established that the new products of
      safety. Clinical tests have been showed the efficiency of including these canned
      goods in the menu of fat patients, also with heavy obesity. Dietetic canned
      ground foods on the base of oceanic fishes with plant additives.

PMID- 10943011
TI  - [Study of the effects of pectin substances under conditions of ontogenesis
      impairment by a complex of chemical factors].
AB  - In the experimental conditions the use of homogenized fruits and vegetables
      mashed potatoes with the addition of the water-extracted apple-pectin Classic AF
      702 as a protector of a toxic action of xenobiotic for the conservation of
      reproductive ability of the organism and the optimum development of posterity.

PMID- 10943012
TI  - [Use of computers for processing thin-layer chromatograms based on an example of
      red food dyes].
AB  - On an example of definition of the forbidden red dye amaranth E123 in a mix with
      other red food dyes (azorubin E122 and ponso 4R E124) the method of quantitative
      processing think level chromatograms was developed. The method includes transfer
      of chromatogram in a digital kind by scanning and processing of the received
      image with the help of the program Adobe Photoshop 5.0. The average values of
      detection of dyes on the developed method make for azorubin, amaranth and ponso
      4R accordingly 95.6, 97.1 and 99.4% with correlation coefficients 0.98, 0.98 and
      0.99.

PMID- 10943013
TI  - [Enteral feeding. History of beginnings and problem development].

PMID- 10943014
TI  - The changing face of the leader.
AB  - Leadership theory has identified leadership as a process or skill of
      transformation of organizations and society. Managerial theorists have seen
      leadership as a role within management, and have argued from a distinctly
      organizational perspective. During the last decade, mental health executives have
      gravitated from the leadership is policy emphasis to one of management
      accommodation to major changes in the health environment. The most noteworthy of
      these changes has been the dominance of private markets in health and the
      introduction throughout the mental health services sector of management
      techniques of managed care. Leadership is once again ascendant as a result of the
      failure of several of these initiatives, notably prior authorization of care, and
      a renewed public policy emphasis on needs of persons who are mentally ill. Major
      opportunities confronting the contemporary leader/manager include advocacy,
      diversity, and information management.

PMID- 10943015
TI  - Who's in charge here anyway? Managing the management split in mental health
      organizations.
AB  - Most mental health organizations are run by chief executive officers (CEOs) who
      are not physicians, with medical directors reporting to the CEOs. In this article
      the historical and organizational origins of this arrangement are reviewed. The
      well known disadvantages of shared management are discussed, as are the less
      obvious advantages. Through case vignettes the authors illustrate how bifurcated
      leadership can promote productive and creative administrative decisions.
      Guidelines are offered for strengthening collaborations between non-medical and
      medical mental health program directors.

PMID- 10943016
TI  - The role of the psychiatrist as medical director: a survey of psychiatric
      administrators.
AB  - Previous surveys of public and community psychiatrists have demonstrated that
      medical directors perform a wider variety of tasks, and experience increased job
      satisfaction, compared to staff psychiatrists. Notwithstanding respondents'
      belief that clinical collaboration tasks contribute most to job satisfaction, the
      performance of administrative tasks is most highly correlated with overall job
      satisfaction. The current survey was undertaken to determine whether these
      findings could be replicated among hospital-based psychiatrists. Demographic and
      job characteristic profiles of hospital-based psychiatrists were clearly
      distinguished from those of community psychiatrists. Despite these differences,
      task profiles and job satisfaction parameters of hospital-based psychiatrists
      were comparable to those previously reported for community psychiatrists.

PMID- 10943017
TI  - Psychiatric leadership and the clinical team: simulated in vivo treatment
      planning performance as teamwork proxy and learning laboratory.
AB  - Leadership is an important consideration at many levels within behavioral
      healthcare systems. The authors developed a training program in a large public
      hospital system that focused on psychiatric leadership and clinical team
      functioning. In a learning laboratory format, they used videotaped patient
      simulations as a stimulus for multidisciplinary treatment planning sessions.
      Structured self-assessments were performed using a preliminary Scale for
      Leadership Assessment and Team Evaluation (SLATE). Videotaping the sessions
      provided an additional team self-assessment tool. Other educational activities
      supplemented the sessions, and teams proposed steps for transferring their
      learning to other units. The authors emphasize that leadership must foster team
      learning, which involves developing adaptive capacities and applying them to new
      clinical situations.

PMID- 10943018
TI  - Trends in domestic violence service and leadership: implications for an
      integrated shelter model.
AB  - Domestic violence is a dangerous and prevalent social problem affecting up to 4
      million women and countless children annually. Shelters offer safety and an
      opportunity for change during the crisis of family violence. These individuals
      also have the potential for retraumatization if leadership within the program
      recapitulates the abuse and coercion felt at home. This article reviews three
      related trends through the lens of power and control--domestic violence policy
      and service, models of leadership, and the study of traumatic stress disorders
      and recovery--and describes their implications for modern shelter service
      delivery.

PMID- 10943019
TI  - Advocating for persons who are mentally ill: a history of mutual empowerment of
      patients and profession.
AB  - The author reviews the history of advocacy for mentally ill individuals. Through
      organizations such as the National Mental Health Association and the National
      Alliance for the Mentally Ill, collaboration among professionals, consumers, and
      concerned citizens is enhanced. The common causes and differences among
      organizations are discussed within the context of how psychiatrists can realize
      leadership strategies to further advance advocacy for mentally ill persons and
      for the profession.

PMID- 10943020
TI  - ANSI update: maximum permissible ambient noise levels for audiometric test rooms.
AB  - The American National Standards Institute (ANSI) specifies maximum permissible
      ambient noise levels (MPANLs) allowed in an audiometric test room to ensure that
      hearing thresholds obtained down to 0-dB HL will not be elevated due to masking
      by ambient noise. MPANLs were originally specified in 1960 and have been revised
      in 1977, 1991, and most recently in 1999. The purpose of this report is to offer
      an overview by providing a historical perspective of the MPANLs recently
      specified by ANSI (ANSI S3.1--1999), the rationale for revising the MPANLs, the
      new computational method used for determining the 1999 MPANLs, the ANSI S3.1-
      1999 octave and one-third octave band MPANLs, and information concerning
      compliance with the new MPANLs.

PMID- 10943021
TI  - Year 2000 position statement: principles and guidelines for early hearing
      detection and intervention programs. Joint Committee on Infant Hearing.

PMID- 10943022
TI  - Ambient noise levels in nursing homes: implications for audiometric assessment.
AB  - Conducting hearing tests and hearing screenings in the nursing home environment
      can be a challenge. One issue which may affect the validity of the test results
      is the level of ambient noise in those facilities when a sound-treated booth is
      not available. This study sampled the ambient noise levels in ten different
      nursing homes and compared those results to the ANSI S3.1--1999 criteria for
      maximum permissible ambient noise levels. Based on the results of this
      investigation, the use of insert earphones for air conduction assessments is
      recommended when a sound-treated booth is unavailable and noise levels exceed the
      ANSI criteria. Other suggestions regarding air-conduction and bone-conduction
      assessments are discussed.

PMID- 10943023
TI  - Computer-automated clinical technique for tinnitus quantification.
AB  - This study addresses the need for uniformity in techniques for clinical
      quantification of tinnitus. Because automation can be an effective means to
      achieve standardization, this laboratory is developing techniques to perform
      computer-automated tinnitus testing. The present study was conducted to
      demonstrate the feasibility of obtaining reliable tinnitus measures using a fully
      automated system. A computer-controlled psychoacoustical system was developed to
      quantify tinnitus loudness and pitch using a tone-matching technique. Hearing
      thresholds were also obtained as part of the procedure. The system generated test
      stimuli and simultaneously controlled a notebook computer positioned in the sound
      chamber facing the patient. The notebook computer displayed instructions for
      responding and relayed response choices through on-screen "buttons" that the
      patient touched with a pen device. Twenty individuals with tinnitus were
      evaluated with the technique over two sessions, and responses were analyzed for
      test-retest reliability. Analyses revealed good reliability of thresholds,
      loudness matches, and pitch matches. These results demonstrate that use of a
      fully automated system to obtain reliable measurements of tinnitus loudness and
      pitch is feasible for clinical application.

PMID- 10943024
TI  - Screening for hearing loss and middle-ear disorders in children using TEOAEs.
AB  - The purpose of this research was to obtain the sensitivity and specificity of
      transient evoked otoacoustic emission (TEOAE) screening procedures compared with
      conventional audiometric pure-tone screening and tympanometry. Pass/refer values
      were obtained from a group of 297 ears of 152 preschool and school-aged children,
      3 to 8 years of age. The sensitivity and specificity of the TEOAE screenings
      compared with the pure-tone screenings were 81% and 95%, respectively. The
      sensitivity and specificity of TEOAE screenings compared with tympanometric
      screenings were 60% and 91%, respectively.

PMID- 10943025
TI  - Influenza and pneumococcal immunization 'blitz' in an inner city area: downtown
      eastside of Vancouver, British Columbia.

PMID- 10943026
TI  - International conference on mosquito control--recommendation.

PMID- 10943027
TI  - Annual report of the National Influenza Surveillance Scheme, 1999.
AB  - An effective national surveillance system is an essential component of a program
      for the control of influenza. The National Influenza Surveillance Scheme includes
      data from sentinel general practice consultations for influenza-like illness,
      laboratory reports of influenza and absenteeism rates from a national employer.
      The 1999 season peaked between May and September with maximal activity between
      July and August. Influenza A was the dominant type in all States and Territories
      with influenza A H3N2 viruses predominating and influenza A H1N1 occurring
      sporadically. There was no evidence of significant drift among the H3N2 isolates
      (A/Sydney-like strains) whereas the H1N1 isolates showed significant antigenic
      changes from the vaccine strain A/Beijing/262/95 and were closely related to a
      new variant A/New Caledonia/20/99. A small peak in influenza B activity occurred
      towards the end of the influenza season and isolates remained closely related to
      the vaccine reference strain B/Beijing/184/93.

PMID- 10943028
TI  - Review of leptospirosis notifications in Queensland and Australia: January 1998
      June 1999.
AB  - The World Health Organization/Food and Agricultural Organization Collaborating
      Centre for Reference and Research on Leptospirosis, Western Pacific Region,
      accredited since 1958, is part of Queensland Health Scientific Services, which
      provide tertiary level support in epidemiology, surveillance, training and
      diagnosis for hospitals and pathology laboratories across the State. Databases
      for leptospirosis on a global, Australian and State-wide basis are maintained on
      site and support public health authorities in Australia, WHO and the
      International Leptospirosis Society. Queensland data collated and analysed from
      leptospirosis questionnaires, and a brief overview of Australian data based on
      questionnaire responses for notified cases from 1998 to June 1999, are
      summarised. The increase in leptospirosis notifications (77%) during 1998
      possibly signalled greater awareness of the disease by clinicians. There was a
      significant increase in leptospirosis notifications for children and students and
      a high rate of hospitalisation of cases. An outbreak in North Queensland during
      the first half of 1999 resulted in 184 notifications with over 50% of cases
      hospitalised. Polymorphic presentation of the disease with severe pulmonary
      haemorrhage is associated in particular with the serovar australis. Serovar
      zanoni continues to be a major cause of severe clinical leptospirosis. Several
      cases were diagnosed in tourists. One of these cases presented with severe
      respiratory distress and required 14 days in hospital.

PMID- 10943029
TI  - A cluster of leptospirosis among abattoir workers.
AB  - In early December 1998, the Northern Rivers Public Health Unit (north-eastern New
      South Wales) was alerted to a possible cluster of leptospirosis cases by the
      supervising scientist of the Western Pacific Region World Health
      Organization/Food and Agricultural Organization Collaborating Centre for
      Reference and Research on Leptospirosis. Investigation revealed a cluster of
      eight leptospirosis cases diagnosed during October and November 1998. All were
      employees of a local meat works. Leptospira serovars isolated included pomona and
      hardjo. Symptoms included headache, fever, muscle pain, sore eyes, abdominal
      pain, vomiting, jaundice, and rash. Five of the eight cases were hospitalised.
      The infection could not be traced to any particular source. Unfortunately,
      records of stock killed during the exposure periods were not available. All cases
      reported exposure to large volumes of animal urine during the course of their
      work. Protective clothing provided included an apron, gloves, and rubber boots.
      All of the patients said they wore rubber boots and seven of the eight wore the
      apron provided. Only two patients reported wearing gloves, the remainder thought
      these were too difficult to work in.

PMID- 10943030
TI  - A re-evaluation of immunisation coverage estimates from the Australian Childhood
      Immunisation Register.
AB  - Immunisation coverage reporting using data from the Australian Childhood
      Immunisation Register is likely to underestimate immunisation uptake. Since 1997,
      several initiatives have been introduced to improve both immunisation uptake and
      notification of immunisation encounters. These initiatives seemed likely to have
      changed previous coverage estimates. Re-calculation of immunisation coverage
      estimates for the previously reported cohorts was undertaken. This used current
      Australian Childhood Immunisation Register data--especially the immunisation
      history form and the impact of catch-up immunisations--to evaluate delayed
      reporting. Previous coverage estimates published in Communicable Diseases
      Intelligence were shown to be at least 2% to 4% below estimates based on data now
      held by the Australian Childhood Immunisation Register, with greater differences
      observed in particular jurisdictions.

PMID- 10943031
TI  - Diphtheria in Australia, recent trends and future prevention strategies.

PMID- 10943032
TI  - Communicable Diseases Surveillance. Presentation of NNDSS data.
AB  - In the March 2000 issue an additional summary table was introduced. Table 1
      presents 'date of notification' data, which is a composite of three components:
      (i) the true onset date from a clinician, if available, (ii) the date the
      laboratory test was ordered, or (iii) the date reported to the public health
      unit. Table 2 presents data by report date for information only. In Table 2 the
      report date is the date the public health unit received the report. Table 1 now
      includes the following summary columns: total current month 2000 data; the totals
      for previous month 2000 and corresponding month 1999; a 5 year mean which is
      calculated using previous, corresponding and following month data for the
      previous 5 years (MMWR Weekly Feb 25, 2000:49(07);139-146); year to date (YTD)
      figures; the mean for the year to date figures for the previous 5 years; and the
      ratio of the current month to the mean of the last 5 years.

PMID- 10943033
TI  - [The use of photo-acoustic stimulation in dental practice].
AB  - Photo-acoustic stimulation provides a powerful stimulation of the central nervous
      system, whereas it relaxes the body. Authors found it useful to eliminate simple
      anxiety, and to reduce salivary secretion in the oral cavity. The combination of
      photo-acoustic stimulation with hypnotic techniques has been found as an
      excellent method to treat oro-facial psychogenic symptoms and denture
      intolerance. In the case of odonto-phobic patients, the combined method has been
      found less effective than hypnotic techniques alone.

PMID- 10943034
TI  - [Large cysts of dental origin in the maxilla].
AB  - The authors give a common survey of clinical and pathological appearance of cysts
      of maxillary sinuses, especially their dental origin. They review the
      possibilities of diagnosis and show the treatment technic they used the past 4
      years on 11 cases. They emphasise the importance of radiological controlling the
      root canal treated teeth and the role of the dentist in instructing the patient
      about this.

PMID- 10943035
TI  - [Therapeutic solution for a combined endo-periodontal lesion. Case report].
AB  - The endo-periodontal lesion may lead to diagnostic and therapeutic difficulties
      in general dental practice. In the present case endo-periodontal inflammation of
      the lower left first molar caused the patient's complaints. The inflammation of
      periodontal and pulpal origin was separated although they simultaneously were
      present in the same time. Endo-periodontal lesion can be treated by endodontic
      and periodontal care and sometimes complemented by surgery. Scaling and
      polishing, as well as root planing were performed following the endodontic
      treatment of distal root, then the tooth was dissected and the mesial root was
      removed. Finally the remained distal part of molar was used as a bridge abutment.
      Combined endo-periodontal lesion can be cured with appropriate treatment as root
      filling, periodontal treatment, supplemented with tooth dissection.

PMID- 10943036
TI  - [Accuracy of two methods of age determination by teeth in the Hungarian
      population].
AB  - The authors tested two methods of age estimation through dental examination. 42
      autopsy cases, ages 18 to 79, were randomly selected by the University Medical
      School of Pecs, Department of Forensic Medicine in 1997-1998. After the
      odontograms were taken, one tooth from each individual was removed from the
      corpses and examined using both the Gustafson's and the Johanson's methods for
      age calculation. The results according to both methods showed a large standard
      deviation. It suggests the necessity of national data base and the re-examination
      of all of the methods tested on different population samples. The authors of this
      paper would like to inspire a revival of Hungarian forensic odontostomatology.

PMID- 10943037
TI  - [The clinical value of determination of fibronectin: the endothelium lesion
      marker in EPH-gestosis].
AB  - Plasma fibronectin concentration, AT III, PAI-1 and platelet count in 115
      patients with gestosis, chronic hypertension and in physiological pregnancy were
      estimated. The obtained results indicate the significant fibronectin increase in
      gestosis patients. The positive correlation between fibronectin concentration and
      gestosis index was found. PAI-1 activity appeared to be the only haemostatic
      parameter which significantly increased in toxaemia. Prophylaxis with
      acetylosalicylic acid did not affect the fibronectin concentration. Fibronectin
      determination allows to differentiate toxaemic patients from the chronic
      hypertension cases. The high specificity and sensitivity of the test implies its
      important clinical role.

PMID- 10943038
TI  - [Urinary trypsin inhibitor in pregnant women with normal and pathological course
      of pregnancy].
AB  - Urinary trypin inhibitor concentration (UTI) was measured by Fritz and all method
      in the groups of women: non-pregnant (I), pregnant (II), in pregnancy complicated
      by EPH-gestosis (III) and in the prolongated pregnancy (IV). Furthermore, in the
      urine from the investigated group the index protein/creatinine was established.
      There was noticed the statistically significant increase in the UTI concentration
      in II, III, IV groups comparing to the non-pregnant group--I, and the increase in
      UTI in III and IV group in comparison to group II. The UTI measurement in the
      pregnant women connected with the index protein/creatinine could be significant
      for diagnosing of the pathology of pregnancy.

PMID- 10943039
TI  - [Comparison of cathepsin-B-like activity and CA 125 assays use in ovarian cancer
      diagnosis].
AB  - BACKGROUND: Determination of serum cathepsin B-like activity was used as a
      diagnostic marker of ovarian cancer. The aim of this study was to compare its
      diagnostic utility with CA 125 assay. METHODS: In 50 patients with epithelial
      ovarian cancer and 20 with ovarian cyst cathepsin B-like activity by fluorimety
      and CA 125 concentration by luminiscence immunoassay, were determined. The
      obtained results were compared by two cut-off values computed from the data
      obtained in healthy controls and ovarian cysts (cathepsin B: 11 and 108 mU/ml; CA
      125: 35 and 135 U/ml), respectively. RESULTS: In differential diagnosis between
      ovarian carcinomas and ovarian cysts cathepsin B shows similar specificity (95%)
      as CA 125 but higher sensitivity (63.5% vs 50%). Both cathepsin B and CA 125 are
      good predictors of tumour response and recurrence CONCLUSIONS: Adding CA 125
      determination to cathepsin B-like activity in the laboratory diagnostics of
      ovarian cancer increased the sensitivity and positive predictive values as
      compared to the use of cathepsin B alone.

PMID- 10943040
TI  - [Radiotherapy and coagulation system in women with cancer of the genital tract].
AB  - The question in the study was whether radiotherapy of women with neoplasma of
      genital tract leads to coagulation activation. The study group consisted of 51
      women with cervical carcinoma (20 cases), endometrial carcinoma (22 cases) or
      ovarian neoplasma (9 cases). Fractionated dose of ionic energy were applied as
      follows: 200 cGy per day, 5 days a week, therapeutic dose of 4,500-5,000 cGy.
      Five coagulological tests were used. Hypercoagulability was found out prior to
      radiotherapy: statistically significantly elevated level of fibrinogen and higher
      thrombin-antithrombin III complexes (TAT) than in the control group. After
      radiotherapy the level of fibrinogen, prothrombin index, aPTT and TAT level did
      not undergo statistically significant changes. IN CONCLUSION: Hypercoagulability
      in women with gynecological malignancy is an effect of the disease itself.
      Radiotherapy does not rise coagulation activation.

PMID- 10943041
TI  - [Laparoscopic myomectomy].
AB  - OBJECTIVES: The aim of our study was clinical analysis of the factors influencing
      on laparoscopic myomectomy. STUDY DESIGN: Retrospective analysis of the operative
      protocols. MATERIAL AND METHODS: Two hundred nineteen women had laparoscopy
      because of unexplained infertility (n = 109) unexplained infertility and myomas
      (n = 41), myomas (n = 36), endometriosis suspicion (n = 20) ovarian cyst (n = 9)
      or pelvic pain syndrome (n = 4). RESULTS: Among 299 myomas 186 were extirpated
      during laparoscopy. In 39 cases suturing of the myometrium was necessary.
      Electrocautery was performed in 27 cases and laser-vaporisation in 8. In 28 women
      the operation was postponed because of small myomas and mainly poor operative
      technique (beginning of the learning curve). In two of them second laparoscopy
      was performed after GnRH therapy. An analysis of the factors which enable
      laparoscopic myomectomy was performed. The most important factors are: size and
      number of the myomas, localization in the myometrium, experienced hands and
      operative room equipment. CONCLUSIONS: Uterine myomas are one of the indications
      to operative laparoscopy. Meticulous analysis of the operative conditions as well
      as the assessment of the team experience should always precede laparoscopy.

PMID- 10943042
TI  - [Prognostic factors in treatment of neoplasms as the dissipative structures].
AB  - The aim of the study is to define the systemic prognostic factors in the neoplasm
      according to thermodynamic theory of cancer a the self-organising dissipative
      structure. As the local, so called "specific" factors seem to be not adequate one
      should look for more general ones. It is shown, that such general factors as
      hormonal state of women' organism, preterm births, lactation, infertility
      treatment are important.

PMID- 10943043
TI  - [Immunological aspects of recurrent spontaneous abortion].
AB  - Recent studies emphasise an important role of immunological mechanisms in
      pregnancy maintenance. Therefore, unravelling mechanisms regulating
      placentogenesis are critical to understanding the pathogenesis of recurrent
      spontaneous abortion (RSA). Author gives review concerning about auto- and
      alloimmunological aspects of RSA.

PMID- 10943044
TI  - [Report from 7th European conference on infectious diseases in obstetrics and
      gynecology].

PMID- 10943045
TI  - Computerized classification of temporomandibular joint sounds.
AB  - Sounds, such as clicking and/or crepitation, evoked in the temporomandibular
      (jaw) joint during function may indicate pathology. Analysis of the reduced
      interference time-frequency distribution of these sounds is of diagnostic value.
      However, visual evaluation is expensive and error prone, and there is, thus, a
      need for automated analysis. The aim of this study was to find the optimal signal
      representation and pattern recognition method for computerized classification of
      temporomandibular joint sounds. Concepts of time-shift invariance with and
      without scale invariance were employed and mutually compared. The automated
      analysis methods provided classification results that were similar to previous
      visual classification of the sounds. It was found that the classifier performance
      was significantly improved when scale invariance was omitted. This behavior
      occurred because scale invariance interfered with the frequency content of the
      signal. Therefore, scale invariance should not be pursued in the classification
      scheme employed in this study.

PMID- 10943046
TI  - Improved heart rate variability signal analysis from the beat occurrence times
      according to the IPFM model.
AB  - The heart rate variability (HRV) is an extended tool to analyze the mechanisms
      controlling the cardiovascular system. In this paper, the integral pulse
      frequency modulation model (IPFM) is assumed. It generates the beat occurrence
      times from a modulating signal. This signal is thought to represent the autonomic
      nervous system action, mostly studied in its frequency components. Different
      spectral estimation methods try to infer the modulating signal characteristics
      from the available beat timing on the electrocardiogram signal. These methods
      estimate the spectrum through the heart period (HP) or the heart rate (HR)
      signal. We introduce a new time domain HRV signal, the Heart Timing (HT) signal.
      We demonstrate that this HT signal, in contrast with the HR or HP, makes it
      possible to recover an unbiased estimation of the modulating signal spectra. In
      this estimation we avoid the spurious components and the low-pass filtering
      effect generated when analyzing HR or HP.

PMID- 10943047
TI  - Characterization of sleep spindles using higher order statistics and spectra.
AB  - This work characterizes the dynamics of sleep spindles, observed in
      electroencephalogram (EEG) recorded from humans during sleep, using both time and
      frequency domain methods which depend on higher order statistics and spectra. The
      time domain method combines the use of second- and third-order correlations to
      reveal information on the stationarity of periodic spindle rhythms to detect
      transitions between multiple activities. The frequency domain method, based on
      normalized spectrum and bispectrum, describes frequency interactions associated
      with nonlinearities occurring in the observed EEG.

PMID- 10943048
TI  - Rejection of the maternal electrocardiogram in the electrohysterogram signal.
AB  - The electrohysterogram (EHG) signal is mainly corrupted by the mother's
      electrocardiogram (ECG), which remains present despite analog filtering during
      acquisition. Wavelets are a powerful denoising tool and have already proved their
      efficiency on the EHG. In this paper, we propose a new method that employs the
      redundant wavelet packet transform. We first study wavelet packet coefficient
      histograms and propose an algorithm to automatically detect the histogram mode
      number. Using a new criterion, we compute a best basis adapted to the denoising.
      After EHG wavelet packet coefficient thresholding in the selected basis, the
      inverse transform is applied. The ECG seems to be very efficiently removed.

PMID- 10943049
TI  - Noise-resistant pulse oximetry using a synthetic reference signal.
AB  - We describe a noise-resistant pulse oximetry algorithm suited to both signal
      reconstruction and oxygen saturation estimation. The algorithm first detects
      relatively clean signal sections from which the heart rate is estimated. The
      heart rate is used to construct a synthetic reference signal that matches an
      idealized pulse signal. An adaptive filter continuously processes the sensor
      signals, reconstructing signals in a linear subspace defined by the reference
      signal. A projective subspace algorithm is then applied to find the oxygenation
      level of the blood. We show that under specific circumstances this algorithm
      solves the sufficiency condition for signal reconstruction in linear saturation
      estimators. The core principle of using a frequency modulated synthetic reference
      signal can be applied to adaptive filtering of other physiological signals
      controlled by the heartbeat, such as blood pressure and electrocardiogram.

PMID- 10943050
TI  - Estimation of 3-D conduction velocity vector fields from cardiac mapping data.
AB  - A method to estimate three-dimensional (3-D) conduction velocity vector fields in
      cardiac tissue is presented. The speed and direction of propagation are found
      from polynomial "surfaces" fitted to space-time (x, y, z, t) coordinates of
      cardiac activity. The technique is applied to sinus rhythm and paced rhythm
      mapped with plunge needles at 396-466 sites in the canine myocardium. The method
      was validated on simulated 3-D plane and spherical waves. For simulated data,
      conduction velocities were estimated with an accuracy of 1%-2%. In experimental
      data, estimates of conduction speeds during paced rhythm were slower than those
      found during normal sinus rhythm. Vector directions were also found to differ
      between different types of beats. The technique was able to distinguish between
      premature ventricular contractions and sinus beats and between sinus and paced
      beats. The proposed approach to computing velocity vector fields provides an
      automated, physiological, and quantitative description of local electrical
      activity in 3-D tissue. This method may provide insight into abnormal conduction
      associated with fatal ventricular arrhythmias.

PMID- 10943051
TI  - Neuro-computing versus linear statistical techniques applied to liver transplant
      monitoring: a comparative study.
AB  - This paper explores the potential for the application of neurocomputing in on
      line monitoring in the liver transplantation domain. It extends our previously
      documented work to provide both an assessment of the performance gains achievable
      by incorporating temporal and dynamical information about the measurements made
      on a patient as well as presenting a novel computerized clinical decision aid for
      this domain. A comparison of the performance of linear and nonlinear
      classification system is made and used to motivate the final selection of the
      diagnostic inputs.

PMID- 10943052
TI  - The forward EEG solutions can be computed using artificial neural networks.
AB  - Study of electroencenphalography (EEG) is the one of the most utilized methods in
      both basic brain research and clinical diagnosis of neurological disorders.
      Recent technological advances in computer and electronic systems have allowed the
      EEG to be recorded from large electrode arrays. Modeling the brain waves using a
      head volume conductor model provides an effective method to localize functional
      generators within the brain. However, the forward solutions to this model, which
      represent theoretical potentials in response to current sources within the volume
      conductor, are difficult to compute because of time-consuming numerical
      procedures utilized in either the boundary element method (BEM) or the finite
      element method (FEM). This paper presents a novel computational approach using an
      artificial neural network (ANN) to map two vectors of forward solutions. These
      two vectors correspond to different head models but with respect to the same
      current source. The input vector to the ANN is based on the spherical head model,
      which can be computed efficiently but involves large errors. The output vector
      from the ANN is based on the spheroidal model, which is more precise, but
      difficult to compute directly using the traditional means. Our experiments
      indicate that this ANN approach provides a remarkable improvement over the BEM
      and FEM methods: 1) the mean-square error of computation was only approximately
      0.3% compared to the exact solution; 2) the online computation was extremely
      efficient, requiring only 168 floating point operations per channel to compute
      the forward solution, and 10.2 K-bytes of storage to represent the entire ANN.
      Using this approach it is possible to perform real-time EEG modeling accurately
      on personal computers.

PMID- 10943053
TI  - Distributed computing for membrane-based modeling of action potential
      propagation.
AB  - Action potential propagation simulations with physiologic membrane currents and
      macroscopic tissue dimensions are computationally expensive. We, therefore,
      analyzed distributed computing schemes to reduce execution time in workstation
      clusters by parallelizing solutions with message passing. Four schemes were
      considered in two-dimensional monodomain simulations with the Beeler-Reuter
      membrane equations. Parallel speedups measured with each scheme were compared to
      theoretical speedups, recognizing the relationship between speedup and code
      portions that executed serially. A data decomposition scheme based on total ionic
      current provided the best performance. Analysis of communication latencies in
      that scheme led to a load-balancing algorithm in which measured speedups at 89 +/
      2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and
      heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy
      dynamic membrane equations exceeded 3.0 with eight distributed workstations.
      Cluster speedups were comparable to those measured during parallel execution on a
      shared memory machine.

PMID- 10943054
TI  - Analysis of passive elastic joint moments in paraplegics.
AB  - In the functional electrical stimulation of the lower extremity of paraplegics to
      achieve standing and walking, a mathematical model describing the passive elastic
      joint moments is essential in order to implement model-based control algorithms.
      In a previous investigation of ten normal persons we had found significant
      coupling of passive, elastic joint moments between neighboring joints due to
      muscle groups that span both joints (biarticular muscles). Thus, we now
      investigated the biarticular coupling in six paraplegic patients. A comparison to
      the averaged results of the ten normal persons showed that while the biarticular
      joint moment coupling due to the gastrocnemius muscle was well preserved in all
      patients, the coupling due to the rectus femoris was greatly reduced and the
      coupling due to the hamstring muscle group was negligible. We offer
      pathophysiologically based explanations for these characteristic differences
      including the speculation that the predominantly extensor-type spasticity in our
      patients exercises mainly the anti-gravity muscles such as the gastrocnemius and
      the rectus femoris, while permitting greater atrophy of the hamstring muscle
      group. A previously presented double-exponential equation that predicts the joint
      moments under consideration of the neighboring joint angles could be fitted well
      to the experimental data.

PMID- 10943055
TI  - Studies of detrusor-sphincter synergia and dyssynergia during micturition in rats
      via fractional Brownian motion.
AB  - In normal humans, the bladder is supposed to empty by a synergistic contraction
      of the detrusor and relaxation of the sphincter during micturition. By contrast,
      suprasacral spinal cord injury (SCI) patients usually will have both of them
      contract simultaneously and result in the so-called detrusor-sphincter
      dyssynergia. In this study, the cystometrograms of the detrusor and the
      electromyograms of external urethral sphincter of intact and SCI female Wistar
      rats are used to investigate the detrusor-sphincter synergia and dyssynergia
      during micturition. Due to the statistical self-similarity of the waveforms, the
      cystometrogram is modeled as discrete-time fractional Brownian motion and the
      electromyogram as discrete-time fractional Gaussian noise. Fractal dimensions of
      both of them are calculated and used as indices in the investigation of synergia.
      Results indicate that, for intact rats, the sphincter muscle is not only active
      but also recruited in a synchronous fashion with the detrusor. Furthermore, clear
      cut measure using the fractal dimensions can be used to diagnose detrusor
      sphincter synergia and dyssynergia.

PMID- 10943056
TI  - Second-order model of membrane electric field induced by alternating external
      electric fields.
AB  - With biological cells exposed to ac electric fields below 100 kHz, external field
      is amplified in the cell membrane by a factor of several thousands (low-frequency
      plateau), while above 100 kHz, this amplification gradually decreases with
      frequency. Below 10 MHz, this situation is well described by the established
      first-order theory which treats the cytoplasm and the external medium as pure
      conductors. At higher frequencies, capacitive properties of the cytoplasm and the
      external medium become increasingly important and thus must be accounted for.
      This leads to a broader, second-order model, which is treated in detail in this
      paper. Unlike the first-order model, this model shows that above 10 MHz, the
      membrane field amplification stops decreasing and levels off again in the range
      of tens (high-frequency plateau). Existence of the high-frequency plateau could
      have an important impact on present theories of high-frequency electric fields
      effects on cells and their membranes.

PMID- 10943057
TI  - A micromachined silicon depth probe for multichannel neural recording.
AB  - A process of making a new type of silicon depth-probe microelectrode array is
      described using a combination of plasma and wet etch. The plasma etch, which is
      done using a low temperature oxide (LTO) mask, enables probe thickness to be
      controlled over a range from 5 to 90 mu. Bending tests show that the probe's
      mechanical strength depends largely on shank thickness. More force can be applied
      to thicker shanks while thinner shanks are more flexible. One can then choose a
      thickness and corresponding mechanical strength using the process developed. The
      entire probe shaping process is performed only at low temperature, and thus is
      consistent with the standard CMOS fabrication. Using the probe in recording from
      rat's somatosensory cortex, we obtained four channel simultaneous recordings
      which showed clear independence among channels with a signal-to-noise ratio
      performance comparable with that obtained using other devices.

PMID- 10943058
TI  - A clinically oriented video-based system for quantification of eyelid movements.
AB  - A field-worthy system was developed to quantify the eyelid movements in clinical
      sites. The system consists of a home-use charge-coupled device video camera, a
      processing unit, and a personal computer. A white marker of 4-mm diameter and 30
      mg weight is attached to the lower margin of the upper eyelid. The processing
      unit automatically detects the vertical displacement of the upper edge of the
      marker. One marker is attached to each eye so that the movements of the both
      eyelids are measured with one camera simultaneously. The measurement error of the
      system was evaluated in experiments on eight healthy subjects and eight patients
      with eyelid paralysis. The mean of the absolute error of peak amplitudes
      occurring in 2 min was 0.81 mm, with the worst error being +1.7 mm. The
      reproducibility of the mean peak amplitude measured on five consecutive days was
      within 1 mm. The mean peak amplitudes of both eyes were measured preoperatively
      and postoperatively for approximately three months for three patients who were
      operated on to remove vestibular schwannoma. The results demonstrated basic
      clinical utility of the system.

PMID- 10943059
TI  - Noise performance design of CMOS preamplifier for the active semiconductor neural
      probe.
AB  - A systematic design guideline is presented for the noise performance of
      preamplifier for semiconductor neural probe which contains on-chip electronic
      circuitry. The overall signal-to-noise ratio (SNR) is calculated considering the
      spectral characteristics of the measured extracellular action potential and the
      low-frequency noise spectrum of the CMOS device from typical fabrication
      processes. An analytical expression of the output noise power is derived, and
      utilized to tailor the frequency response and device parameters which are
      controllable by the circuit designer. An analysis of the output SNR of a two
      stage CMOS differential amplifier is given and the major factors which have
      significant effects on the SNR are determined. We showed that a little deviation
      of the input device sizes and transconductance ratio from the optimal values can
      significantly deteriorate the SNR. Quantitative information of the preamplifier
      circuit parameters for satisfactory noise performance is provided.

PMID- 10943060
TI  - Can the light-addressable potentiometric sensor (LAPS) detect extracellular
      potentials of cardiac myocytes?
AB  - The light-addressable potentiometric sensor (LAPS) measures localized photo
      induced currents from a silicon wafer, which are dependent on the local surface
      potential and on the intensity of the light pointer. In this study the ability of
      the LAPS to record extracellular potentials of adherent cells was investigated.
      Time dependent LAPS photocurrent signals that correlated in time with
      contractions were recorded from beating cardiac myocytes cultured on LAPS
      surfaces. Signals could be recorded both when the LAPS was biased to working
      points where the photocurrent was maximally sensitive to potential changes and
      when it was biased to working points where the photocurrent was insensitive to
      changes in surface potential. Therefore, signals could not be predominantly
      created by changes in extracellular potential and might be related to mechanical
      contractions. One possible explanation might be, that the cell-induced modulation
      of photocurrents arose as a result of cell shape changes. Such alterations in
      cell shape might have focused and defocused the light pointer and, thus,
      modulated its intensity. To further test this hypothesis, height changes of
      beating cardiac myocytes were measured with an atomic force microscope (AFM).
      They were found to match well with signals derived from LAPS measurements.
      Therefore, it can be concluded, that LAPS signals were mainly determined by the
      periodic changes in shape of beating heart cells, and this interference precludes
      the measurements of extracellular electrophysiological potentials from these
      cells.

PMID- 10943061
TI  - Evidence for roles of the activating function in electric stimulation.
AB  - The hypothesis that the activating function drives transmembrane voltage changes
      (delta Vm) has been tested in hearts. Optical delta Vm were measured during
      activating functions produced with nonuniform and uniform transparent electrodes.
      When a nonuniform electrode was used to produce [equation: see text], the signs
      of delta Vm and [equation: see text] matched. The extracellular voltage
      gradients, often assumed important, did not predict delta Vm. When a uniform
      electrode was used to eliminate [equation: see text], the signs of delta Vm
      matched the signs of [equation: see text] estimated from variations in heart
      width. Demonstration of the activating function as a determinant of stimulation
      may improve research and therapy that use electric stimulation.

PMID- 10943062
TI  - Digital X-ray stereophotogrammetry for cochlear implantation.
AB  - Multielectrode, intracochlear implant systems are effective treatment for
      profound sensorineural hearing loss. In some cases, these systems do not perform
      well, which may be partially due to variations in implant location within the
      cochlea. Determination of each electrode's position in a patient's inner ear
      provides an in vivo basis for both the cochlear modeling of electrical fields and
      the future design of electrode arrays that deliver electrical stimulation to
      surviving auditory neurons, and may improve speech processor programming for
      better speech recognition. We developed an X-ray stereophotogrammetric approach
      to localize implanted electrodes in three dimensions. Stereophotogrammetry of
      implanted electrodes is formulated in weak perspective geometry, with knowledge
      of a three-dimensional (3-D) reference structure and electrode positions in each
      of two digital stereo-images. The localization error is theoretically,
      numerically, and experimentally quantified. Both numerical and experimental
      results demonstrate the feasibility of the technique.

PMID- 10943063
TI  - Vibration arthrometry in patients with knee joint disorders.
AB  - Physiological patellofemoral crepitus (PPC) is the vibration signal produced by
      the knee joint during slow motion (less than 5 degrees per second), which can be
      measured by vibration arthrometry (VAM). By using the autoregressive (AR) model
      for the PPC signals of patients with knee osteoarthritis, the study analyzes the
      PPC signals to evaluate the condition of patellar-femoral joint cartilage.
      Accordingly, we can divide osteoarthritis into three types, type 1: the cartilage
      of patellar-femoral joint is intact, the osteoarthritis found in the femoral
      tibial joint surface; type 2: degeneration occurs in the surface cartilage of
      both the femoral-tibial joint and the femoral trochlea, but not on the patellar
      surface; type 3: both patellar-femoral and femoral-tibial joints have
      osteoarthritis. For the analysis, the intraclass distance of AR coefficients and
      spectral power ratio of dominant poles are adopted. Based on the proposed method,
      two cases of type 1, six of type 2, and 28 of type 3 were found in 36 cases of
      knee osteoarthritis. This is in agreement with the operative findings. For
      comparison, the PPC signals of 10 subjects with normal knees (without pain or
      wound history) were also measured. The results of analysis of the 10 normal
      subjects were consistent and clearly differentiable from those of the
      osteoarthritis patients. Therefore, the proposed method is efficient for the
      analysis of the condition of patellar-femoral joint cartilage and VAM may become
      an alternative way of noninvasive diagnosis of knee osteoarthritis.

PMID- 10943064
TI  - Limit cycle oscillations in pacemaker cells.
AB  - In recent decades, several mathematical models describing the pacemaker activity
      of the rabbit sinoatrial node have been developed. We observe that membrane
      voltage and membrane charge are treated as independent dynamic variables in some
      of those models, resulting in an infinite number of limit cycles. Then we display
      numerical results from a new model where membrane voltage (v) is not a dynamic
      variable, and observe a limit cycle oscillation that can be reached from many
      different initial conditions.

PMID- 10943065
TI  - Comments on "Fusion of body surface potential and body surface Laplacian signals
      for electrocardiographic imaging".

PMID- 10943066
TI  - Intratypic differentiation & partial nucleotide sequencing of poliovirus isolates
      of northern India.
AB  - The potential resolving power of molecular epidemiological studies has enhanced
      the precision and reliability of poliovirus (PV) surveillance. PV has an error
      prone RNA polymerase responsible for rapid evolution of genome (approximately 10(
      2) nt substitution/site/year), during inter and intra-human passages. The present
      study included a serotyped panel of 60 PV (42 PV type-1, 13 PV type-2 and 5 PV
      type-3) isolated during 1997. They were differentiated into vaccine (Sabin) and
      wild strains by two methods viz., genotype specific RNA probe hybridization (Rpro
      Hy) based on genotypic variability; and ELISA that uses cross-absorbed antiserum
      (Pab-E) based on phenotypic variability. For obtaining information on molecular
      epidemiology, partial nucleotide sequencing (VP1/2A region) of five clinical PV
      isolates was also done. Three of the 60 isolates (two PV type-1 and one PV type
      3) intratyped, could not be differentiated correctly by either method. Genotypic
      characterization of PV isolates was done for confirmation of intratyping results.
      All five wild PV1 sequenced belonged to the same genotype (> 85% homology) and
      sequence divergence among the strains was < or = 4.5 per cent. This indicated
      circulation of a single genetic lineage in the area.

PMID- 10943067
TI  - Antigen distribution pattern of Japanese encephalitis virus in Culex
      tritaeniorhynchus, C. vishnui & C. pseudovishnui.
AB  - Distribution of Japanese encephalitis (JE) virus antigen in different tissues of
      mosquitoes was studied in three species viz., Culex tritaeniorhynchus, C. Vishnui
      and C. pseudovishnui. Overall per cent positivity was higher in the
      intrathoracically infected as compared to the orally infected mosquitoes,
      suggesting the existence of a midgut barrier. The cells at the junction of the
      foregut-midgut, and midgut-hindgut showed intense fluorescence from the second
      day post feeding onwards. This suggests that the dissemination of virus takes
      place from these regions of the gut. A small number of salivary glands were found
      negative even though fluorescence was seen in the respective head squashes,
      suggesting involvement of the salivary gland barrier in these mosquitoes. Though
      there was no difference in the salivary gland positivity between these three
      species, the salivary gland area positivity was high in C. tritaeniorhynchus
      mosquitoes. Presence of virus antigen in the ovaries and developing eggs of these
      three species on the third day suggests the possibility of transovarial
      transmission of virus even in the first gonotrophic cycle which may have
      epidemiological importance.

PMID- 10943068
TI  - Production of siderophores & effect of iron restriction on the protein profiles
      of Aeromonas species isolated from water & patients suffering from acute
      diarrhoeal disease.
AB  - Among 48 strains of Aeromonas species, 21 isolates from patients suffering from
      acute diarrhoea and 27 from metropolitan water samples grown under iron
      restricted conditions, 45 strains produced siderophores. Forty one of the 46
      strains tested produced siderophores on chrome azurol S (CAS) agar, while 43
      isolates did so when the culture supernatants of the bacterial isolates grown in
      minimal medium were assayed with chrome azurol S assay solution. The whole cell
      protein profiles of A. hydrophila strains grown under iron restricted conditions
      expressed new proteins that were not detected in those cultured in iron rich
      conditions. Five high molecular weight proteins ranging from 70 to 96 kDa were
      distinctly absent in cultures grown in the presence of iron, indicating their
      role in iron acquisition by the aeromonads.

PMID- 10943069
TI  - Evaluation of E test for susceptibility testing of Mycobacterium tuberculosis to
      primary anti tubercular drugs.
AB  - BACKGROUND & OBJECTIVES: Antimicrobial susceptibility tests for tuberculosis take
      weeks and delayed therapy can lead to an increase in disease incidence. The E
      test is a new concept for minimum inhibitory concentrations (MIC) determinations
      for antimicrobial agents that is based on a predefined antibiotic gradient on a
      plastic strip calibrated with a continuous logarithmic MIC scale covering 15 two
      fold dilutions. The present study was undertaken to evaluate E test strips for
      susceptibility testing of Mycobacterium tuberculosis. METHODS: Twenty five
      clinical isolates of M. tuberculosis were tested for the four first line
      antitubercular drugs by E test and were compared with standard proportion method.
      The inoculum turbidity was adjusted to McFarland 3.0 standard and agar plates
      (Middle brook 7H11 agar) were inoculated and preincubated (37 degrees C in 7-10%
      CO2) for 24 h after which time, the E test strips were placed on the agar surface
      which were incubated under same conditions. The MIC was interpreted as the point
      at which the ellipse intersected the 'E test' strip as described in E test
      technical guide. RESULTS: Of the 25 strains, susceptibility as determined by both
      methods for isoniazid (INH), rifampin, ethambutol and streptomycin was found in
      22 (88%), 20 (80%), 24 (96%) and 18 (72%) strains respectively. Agreement between
      E test and proportion method was 96 per cent for INH, 92 per cent for rifampin
      and 100 per cent for ethambutol and streptomycin each. However, sensitivity could
      be predicted after 7-10 days by E test and exact MIC could also be determined.
      INTERPRETATION & CONCLUSIONS: E test method was found to be rapid, accurate,
      reliable and easy to perform. It can be employed for routine susceptibility
      testing for antitubercular drugs.

PMID- 10943070
TI  - Association of vitamin D receptor genotypes with the susceptibility to pulmonary
      tuberculosis in female patients & resistance in female contacts.
AB  - To find out whether non-HLA genes such as vitamin D receptor (VDR) and
      Interleukin-1 receptor antagonist (IL-1RA) are associated with the susceptibility
      or resistance to pulmonary tuberculosis (PTB), genotyping of VDR, and IL-1RA
      genes was carried out in PTB patients (n = 202) and control subjects (n = 109).
      No marked difference in the frequency of the variant VDR genotypes was seen
      between the PTB patients as a whole and control subjects. However, a significant
      (P < 0.02) increase of VDR genotype tt (mutant homozygotes) was seen in the
      female PTB patients when compared to female contacts (spouses of male patients).
      Similarly, a significant (P < 0.02) increase of TT genotype (wild type
      homozygotes) was observed in female contacts compared to female patients. An
      opposite picture of the VDR genotype frequencies was seen in male patients and
      male contacts (spouses of female patients). Moreover, an increased frequency of
      tt genotype was observed in quiescent male patients compared to male relapse
      patients while no such difference was observed in female quiescent and relapse
      patients. These differences were not significant. No difference in the genotype
      frequencies of IL-1RA genes was seen between PTB patients and control subjects.
      The present study suggested that the genotype tt of vitamin D receptor gene may
      be associated with susceptibility to pulmonary TB in female patients, and the
      genotype TT may be associated with resistance in female contacts.

PMID- 10943071
TI  - Significance of circulating immune complexes in myasthenia gravis.
AB  - In this study, circulating immune complexes (CICs) were isolated and
      characterized in the sera of myasthenia gravis (MG) patients with thymoma and MG
      patients without any thymic lesions. High titres of antistriational antibodies in
      the CICs were demonstrated by an indirect immunofluorescence (IF) method in 60
      per cent (15/25) MG patients with thymoma. The CICs showed a steady decrease in
      these 15 patients during the post thymectomy period. Antistriational antibodies
      in the CICs of MG patients without thymic lesions were not detected by IF method.
      The results of this study emphasised the usefulness of estimation of CICs in the
      overall management of MG patients with thymoma.

PMID- 10943072
TI  - The effects of dioxin on reproduction and development.
AB  - The developmental effects of dioxin are important because of the high sensitivity
      of mammals as well as the irreversibility and longevity of the effects. In animal
      experiments, exposure to dioxin during pregnancy and lactation induce various
      functional effects on offspring at very low doses. In humans, even if there is no
      exposure to dioxin after birth, there might be effects on thyroid function in
      infants exposed to dioxin from breast milk. In this report, low-dose
      developmental effects of dioxins on offspring in animal experiments and human
      studies were reviewed. In terms of risk assessment, methods to describe
      dosimetry, models to describe dose-response and approaches to express health risk
      are discussed.

PMID- 10943073
TI  - Occupational dermatoses from one-component epoxy coatings containing a modified
      polyamine hardener.
AB  - In an electronics plant, 2 one-component epoxy coatings containing a modified
      polyamine hardener were used as covering materials for protecting important
      information on police radio circuit boards. The resinous parts of the coatings
      consisted of epoxy resins based on diglycidyl ether of bisphenol F. The hardener
      was a dimethylaminopropylamine (DMAPA)-epoxy adduct and contained about 0.16%
      free DMAPA. Of 105 workers, 17 (16%) were diagnosed to have work-related
      dermatitis but were not patch tested. The hands were the commonly affected region
      (13 out of 17 cases). The latent period of dermatitis was very short (mean 21.5
      days). The work-related dermatoses were closely related to the type of work and
      working periods. In the present study, hand protection and the introduction of
      automation have been demonstrated to be useful for the prevention of epoxy
      coating dermatitis.

PMID- 10943074
TI  - Associations of body mass index and percentage body fat by bioelectrical
      impedance analysis with cardiovascular risk factors in Japanese male office
      workers.
AB  - To determine whether body mass index (BMI, kg/m2) or percentage body fat (%BF) by
      bioelectrical impedance analysis (BIA) better reflects the cardiovascular risk
      profile, we examined the associations among BMI, %BF by BIA, and cardiovascular
      risk factors (systolic blood pressure (SBP), diastolic blood pressure (SBP), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), LDL-C/HDL-C ratio, and triglycerides (TG)) in 1,217 Japanese male office
      workers aged 25 to 59 years. From stepwise regression analyses of cardiovascular
      risk factors on age, BMI, alcohol intake, and cigarette smoking, significant
      correlates were, in the order of relative importance: age, BMI, and alcohol
      intake for SBP and DBP (the cumulative percentage of variation; 14.9% and 21.3%,
      respectively); age, BMI, and alcohol intake (negative) for LDL-C (11.0%); BMI
      (negative), alcohol, and cigarette smoking (negative) for HDL-C (19.9%); BMI,
      alcohol intake (negative), age, and cigarette smoking for LDL-C/HDL-C ratio
      (23.1%); and BMI, age, cigarette smoking, and alcohol intake for Log TG (21.7%).
      From stepwise regression analyses using %BF by BIA as an independent factor, %BF
      by BIA was also significantly associated with each cardiovascular risk factor,
      but the decrease in explained variance for each cardiovascular risk factor was
      0.2-4.5%, compared with the model using BMI as an independent factor. These
      results suggest that BMI may better reflect blood pressure or serum lipid profile
      than %BF by BIA.

PMID- 10943075
TI  - Study on work load of matrons under shift work in a special nursing home for the
      elderly.
AB  - In order to find out the work load of matrons under shift work in a special
      nursing home for the elderly (SNH), six healthy female matrons volunteered to
      participate in the present study. For each subject, care working time, heart
      rate, walking steps, estimated energy expenditure and working time in different
      postures were determined during day shift work (540 min) and night shift work
      (960 min). Although the time on duty, working and recess were significantly
      longer in night shift work than day shift work, the percentages of working and
      recess time to duty time were nearly the same regardless of shift work. The
      longest care work in each shift work was individual care of residents in the SNH.
      The maximum, minimum and mean heart rate and percentages to estimated maximal
      heart rate were similar in each shift work. Although total walking steps in night
      shift work were significantly larger than those in day shift work, steps per hour
      did not differ between them. The estimated total energy expenditure (kcal) was
      significantly higher in night shift work than in day shift work; however, the
      work intensity (kcal/kg/min) was significantly higher in day shift work. The
      longest length and larger percentage of working time were observed in standing
      posture in each shift work. These findings suggest that physical activity and
      energy expenditure of matrons under either shift work in the SNH seem to be high.
      Further studies are needed to clarify the work load of matrons engaged in SNH to
      formulate countermeasures.

PMID- 10943076
TI  - The chemiluminescent response from human monocyte-derived macrophages exposed to
      various mineral fibers of different sizes.
AB  - The aims of the present work were to quantify ability to induce lucigenin
      dependent chemiluminescence (CL) from 6-9 day-old human monocyte-derived
      macrophages exposed to various mineral fibers, and to examine the relationship
      between ability to induce CL and fiber size. All fiber samples induced the CL
      response from the cells. The relationship between the number of fibers
      administered and the CL response was examined on all fiber samples by linear
      regression. The slope of the regression line supplies an approximation of the
      ability to induce CL. A strong increased correlation between geometric-mean
      length of fibers and ability to induce CL was observed for the seven fiber
      samples more than 6 microns in length (r = 0.9895). Geometric-mean width and the
      ability to induce CL showed no correlation. However, among the two fiber samples
      having a similar length distribution (RF2, RF3), the wider width sample (RF3, 2.4
      microns) demonstrated lower ability to induce the CL than the narrower width
      sample (RF2, 1.1 microns). The present method enabled comparison of ability to
      induce lucigenin-dependent CL from human monocyte-derived macrophages for various
      mineral fibers with different sizes. Our findings suggested the possibility that
      ability to induce O2- production increased with fiber length, when fibers are
      longer than approximately 6 microns.

PMID- 10943077
TI  - Combined effects of traffic and electromagnetic fields on the immune system of
      fertile atopic women.
AB  - Object of this preliminary study was the immune response to high or low frequency
      electromagnetic fields (ELMF) of non-atopic and atopic fertile women with uniform
      exposure to toxic compounds produced by traffic. Women were divided in group A
      (non-atopic, non-exposed to ELMF); B (atopic, non-exposed to ELMF); C (non
      atopic, exposed to ELMF); D (atopic, exposed to ELMF). "In vitro" cell
      proliferation of peripheral blood mononuclear cells (PBMC) of atopic women
      (groups B and D) stimulated by phytohaemoglutinin (PHA) was reduced. The ELMF
      exposed women (groups C and D) showed lower levels of blood NK CD16(+)-CD56+
      lymphocyte subpopulations and of "in vitro" production of interferon-gamma (both
      spontaneously and in presence of PHA) by PBMC, suggesting that ELMF reduces blood
      cytotoxic activity. Serum IgE of the atopic women exposed to ELMF (group D) was
      higher than that of the other groups. Linear discriminant analysis including
      serum zinc and copper (essential enzymes for immune functions), blood lead and
      urinary transtrans muconic acid, a metabolite of benzene (markers of exposure to
      traffic) and key parameters of immune functions (CD16(+)-CD56+ lymphocyte subset,
      serum IgE, interferon-gamma produced by PBMC in presence of PHA, stimulation
      index of blastogenesis) showed absence of significant difference between groups A
      and C and a marked separation of groups B and D. This datum suggests that ELMF
      have a greater influence on atopic women exposed to traffic than on non-atopic
      ones.

PMID- 10943078
TI  - Asbestos exposure in a shipyard area, northeastern Italy.
AB  - The Monfalcone area, northeastern Italy, is a small industrial district
      (population 60,000), with a large shipyard. In order to monitor asbestos exposure
      in this area, a series of 3,640 necropsies, carried out at the Monfalcone
      Hospital between October 1979 and September 1998, were investigated. The thoracic
      cavities were examined for pleural plaques; these were classified into three
      classes (small, moderate, large). Routine histological sections of lung tissue
      were examined for asbestos bodies. Isolation and counting of asbestos bodies were
      performed in 1,075 cases. Lifetime occupational data were collected in 1,277
      cases. Pleural plaques were observed in 70.5% among men and in 23.8% among women.
      The prevalences of pleural plaques did not show significant variations during the
      study period. Asbestos bodies were found on routine lung sections in 23.7% of men
      and 3.0% of women. The shipyard workers, the most numerous category in the
      series, were characterized by high prevalence of pleural plaques (total 86.7%,
      large 32.4%), high prevalence of asbestos bodies on routine lung sections
      (35.3%), and high amounts of lung asbestos bodies after isolation. The present
      data indicate that asbestos exposure may reach alarming levels in the shipyard
      areas.

PMID- 10943079
TI  - Chronic inhalation toxicity and carcinogenicity studies of 3-chloro-2
      methylpropene in BDF1 mice.
AB  - Chronic toxicity and carcinogenicity studies of 3-chloro-2-methylpropene (CMP),
      which has been widely used as an insecticide and chemical intermediate, were
      carried out in BDF1 mice. CMP was administered to mice in groups of 50 male and
      50 female mice by the inhalation route 5 days per week for 104 weeks at doses of
      0, 50, 100 or 200 ppm. Male and female mice in the CMP-exposed groups had
      decreased body weight but no noticeable clinical signs when compared with the
      control group. Dose-related increases in the incidences of gastric mucosal
      hyperplasia and squamous cell papilloma were observed in both sexes, and squamous
      cell carcinoma was observed in only one male mouse in the 100 ppm group. An
      increased incidence of Harderian gland adenoma in female mice was also
      recognized. In the nasal cavity, eosinophilic exudate associated with atrophy of
      olfactory epithelia, respiratory metaplasia of olfactory epithelia and olfactory
      gland, and eosinophilic changes in respiratory and olfactory epithelia were
      increased in both sexes.

PMID- 10943080
TI  - Effects of sulfur dioxide inhalation on plasma vitamin C and ceruloplasmin in
      ageing rats.
AB  - Ageing is associated with changes in physical characteristics and decline of many
      physiological functions. It has been accepted that the oxidative stress or damage
      induced by free radicals is related to ageing. Three age groups, 3, 12 and 24
      months, were used to investigate whether age-associated changes in some
      parameters (vitamin C and ceruloplasmin) in the plasma of male Swiss-Albino rats
      and to observe possible effects of sulfur dioxide (SO2) for 6 weeks on the same
      parameters. Rats were exposed to 10 ppm SO2 1 hr/day, 7 days/week for 6 weeks.
      Control groups were exposed to filtered air in the same conditions. An effect of
      SO2 on those parameters was observed. The level of vitamin C and ceruloplasmin in
      plasma were decreased in young, middle-aged and old groups in response to SO2.

PMID- 10943081
TI  - Construction of an exposure chamber for animals and its use for inhalation
      exposure to welding fumes and gases.
AB  - An inhalation exposure system, consisting of an inhalation chamber and an
      generating and feeding device for welding fumes and gases with a welding robot,
      was constructed and examined for its application to experimental toxicology for
      ventilatory responses of conscious rats to welding fumes and gases. The exposure
      system allowed an inhalation of fresh welding fumes and gases, and could supply
      airflow containing stable concentrations of fumes and ozone even the levels
      exceeding those corresponding occupational exposure limit values were supplied
      into the exposure chamber. The air temperature in the chamber was kept constant
      under rat's physiological conditions. Rats were exposed to fresh welding fumes
      and gases and examined for their ventilatory responses with a body plethysmograph
      in the chamber. A transient increase in breathing frequency with a concomitant
      decrease in the tidal volume was observed within several minutes immediately
      after the start of welding operation. The rapid, shallow breathing response
      disappears after repeated exposures, indicating rapid adaptation of this
      ventilatory response to inhalation of welding fumes and gases.

PMID- 10943082
TI  - Effect of platinum coordination complex (PtCx) on citrate uptake by rat renal
      brush border membrane vesicles (BBMV): direct effect of cisplatin.
AB  - Platinosis (severe dermatitis and/or asthma) may be broadly defined as the
      effects of soluble platinum salts on people exposed to them occupationally.
      Platinum coordination complexes are widely used in the treatment of a variety of
      solid tumors. However, the clinical use of cisplatin (the most useful agent) is
      limited by the development of nephrotoxicity. High dose exposure of soluble
      platinum could possibly induce nephrotoxicity, occupationally. Urinary citrate is
      freely filtered at the glomerulus, and its reabsorption in the proximal tubule is
      the major determinant of rate. In this study, we exposed isolated rat renal brush
      border membrane vesicles (BBMV) to cisplatin and examined their citrate uptake
      characteristics. BBMV were prepared by the divalent cation precipitation method.
      Citrate uptake was measured by the Millipore rapid membrane filtration technique.
      The preincubation of BBMV with 5 mM of cisplatin for 4 and 8 hours significantly
      inhibited citrate uptake compared with that of the control BBMV. These findings
      might contribute to nephrotoxicity in cisplatin therapy.

PMID- 10943084
TI  - Is there a better way to die? Isn't it time we talk about it?

PMID- 10943083
TI  - Creating notifications tailored for individual workers by using a database: a
      conceptual framework and its application.
AB  - Although prevention strategies to assure good mental health in the workplace have
      become important, worker notification in studies using psychometric tests has
      rarely been discussed. Until now it has been difficult to prepare a large number
      of notifications that are tailored well for individual workers. We have developed
      a system to create notifications that explain the results for individual workers
      in plain language using a relational database (RDB). First, scores for each test
      were divided into categories and the workers' data was classified. Then,
      explanations were written for each category. RDB software read component files
      into a database file, integrated all data, and printed out notifications. After
      the system was developed, we realized its high potential for use in occupational
      health care, as well as in many other fields. We also report an example of its
      application.

PMID- 10943085
TI  - Assignment of benefits is 'standard practice'.

PMID- 10943086
TI  - The IOM report on medical errors ... medicine under a microscope.

PMID- 10943087
TI  - Let's help the children.

PMID- 10943088
TI  - Organ donation.

PMID- 10943089
TI  - Factors associated with the vaccination of international travelers: a
      multivariate analysis.
AB  - Travel medicine practice in the United States has not been extensively studied.
      This study included 1078 consecutive patients who presented to a university-based
      travel medicine clinic from 1990 through 1994. Analyses of patient demographics,
      clinic attendance, itineraries, and vaccinations were conducted. Mean patient age
      (+/- SD) was 37.4 +/- 16.2 years; 626 (58.1%) of the patients were male. Travel
      duration was 103.1 +/- 242.3 days (median, 21 days), and lead time (defined as
      the time between clinic presentation and departure for the purpose of this study)
      was 23.8 +/- 26.5 days (median, 16 days). Destination was the strongest
      independent factor affecting vaccination practices. A lead time of 31 or more
      days was associated with significantly elevated odds ratios for all
      immunobiologicals except immune globulin. These findings underscore the need to
      educate the traveling public, healthcare providers, and the travel industry about
      the benefits of seeking medical consultation at least 1 month prior to
      international travel.

PMID- 10943090
TI  - Carcinoid tumor in Meckel's diverticulum: laparoscopic treatment and review of
      the literature.
AB  - Meckel's diverticulum is a common anomaly of the small intestine that occurs in
      approximately 2% of the population, often found incidentally at the time of
      abdominal exploration. Carcinoid tumors in a Meckel's diverticulum have been
      reported in only 111 cases. The author describes a patient who presented for
      elective cholecystectomy and who during laparoscopy was found to have an abnormal
      appearing ileal diverticulum. The resected specimen contained a carcinoid tumor.
      The decision-making process in treating these patients is reviewed along with a
      discussion of the laparoscopic treatment of intra-abdominal pathologic conditions
      found incidentally at the time of elective surgery.

PMID- 10943091
TI  - Benzodiazepine toxicity with profound suppression of the electroencephalogram.
AB  - The authors report the case of a 60-year-old man with respiratory distress
      secondary to exacerbation of chronic obstructive pulmonary disease, right lower
      lobe pneumonia, and severe bronchospasm. High doses of lorazepam were given
      intravenously after failure to control bronchospasm and agitation with
      bronchodilators and mucolytic agents; the patient was unresponsive to all stimuli
      while receiving lorazepam. Electroencephalography revealed a profoundly
      suppressed pattern without accompanying low-voltage fast activity--this was
      reversible following withdrawal of the lorazepam.

PMID- 10943092
TI  - Use of a computer-assisted clinical case (CACC) SOAP note exercise to assess
      students' application of osteopathic principles and practice.
AB  - Osteopathic medical students are future osteopathic physicians, and how they view
      the manipulative aspect of patient care will have an effect on the
      distinctiveness of osteopathic medicine. To encourage students' application of
      osteopathic principles and practice, a Web-based computer-assisted clinical case
      (CACC) was designed, for which students were required to submit a SOAP
      (Subjective, Objective, Assessment, Plan) note. Results from the CACC-SOAP note
      exercise indicate that the experience engages medical students and can determine
      the students' abilities to recognize osteopathic principles in patient care.

PMID- 10943093
TI  - Clinical research: the process.

PMID- 10943094
TI  - The mechanism of anatomical structure in its relation to osteopathy. 1911.

PMID- 10943095
TI  - The emerging concept of the osteopathic lesion. 1948.

PMID- 10943096
TI  - [Self-treatment instruction of patients with type 1 diabetes. Report from
      hospitals belonging to Working Group for Structured Diabetes Therapy (ASD) in
      Germany 1998].
AB  - AIM: Intensified insulin therapy is the therapy of choice for patients with
      diabetes Type I. Intensified insulin therapy includes an basis-bolus insulin
      injection regimen or continuous subcutaneous insulin infusion, several times
      daily blood glucose self-monitoring, self-adaptation of insulin dosages by the
      patients themselves and a far-reaching liberalization of nutrition. The patients
      learn self management of diabetes therapy in a structured treatment and teaching
      program. The effectivity of this program is evaluated in the routine care.
      PATIENTS AND METHOD: A peer-review quality circle was formed as an official
      working group of the German Diabetes Association based on the formation of a
      working group (Arbeitsgemeinschaft fur Strukturierte Diabetestherapie [ASD]) of
      presently 135 general internal medicine departments from city, country and
      university hospitals throughout the country. The group attempted to document and
      to improve the quality of structure and process of Type-I diabetes care in its
      participating institutions by a system of peer supervision. Systematic follow-up
      examinations of 50 consecutive Type-I diabetic patients 12 to 15 months after
      participation in the program confirm the outcome quality. The working group meets
      every year to discuss the results non anonymously. A PC-system (DIQUAL) was
      developed for collecting, checking and pooling of the outcome data. RESULTS: From
      1992 a representative sample of 6.555 patients with Type-I diabetes was examined.
      At the first time in 1998 the outcome results of 1.789 patients were analyzed
      depending on the therapeutic goals. In patients with a high initial HbA1c (> or =
      8%) an improvement from 9.8 to 8.0% was reached going together with a reduction
      of severe hypoglycemia from 0.23 to 0.13/patient/year. In patients with an
      acceptable initial HbA1c (< 8%) the frequency of severe hypoglycemia could be
      reduced from 0.65 to 0.24/patient/year without any deterioration in metabolic
      control. Furthermore the incidence of ketoacidosis with hospitalization and the
      inpatient days were reduced significantly. CONCLUSION: A substantial improvement
      of HbA1c and reduction of acute complications, especially of severe hypoglycemia
      in patients with Type-I diabetes were reached by participation in a structured
      teaching and treatment programme in clinical routine care.

PMID- 10943097
TI  - [Patients with diabetes mellitus: psychosocial stress and use of psychosocial
      support: a multicenter study].
AB  - BACKGROUND: In a multicenter study the association of psychosocial stress and the
      use of psychosocial support in patients with diabetes mellitus was evaluated.
      PATIENTS AND METHOD: In a sample of 410 patients with diabetes mellitus (Type I:
      n 157, Type II: n = 253) stress in different facets of daily life was assessed
      using the revised Questionnaire on Stress in Patients with Diabetes (QSD-R). Self
      constructed items were used to assess the use of psychosocial support during the
      course of the illness. Diabetics with a mean global stress score above standard
      deviation were defined as extremely handicapped and compared to the less
      handicapped sample. RESULTS: Extreme psychosocial stress could be found in 68
      diabetics (16.6%). Not the type of diabetes but the use of insulin within the
      Type-II diabetic sample revealed an impact on psychosocial stress. Diabetics with
      extreme psychosocial stress showed worse diabetic control compared to less
      stressed diabetics. Profiles of psychosocial stress showed maximal stress with
      regard to depression in both types of diabetes; this was followed by fear of
      hypoglycemia in the sub-sample of Type I and physical complaints in the sub
      sample of Type-II diabetics. Family members, primary care physicians and
      diabetologists were the main sources of psychosocial support. CONCLUSION: A
      considerable number of diabetic patients suffers from extreme psychosocial stress
      often associated with poor diabetic control. These patients need psychosocial
      care which should primarily be offered in diabetologic centers incorporating both
      the patients' family and family background.

PMID- 10943098
TI  - [Long-term toxic sequelae of the treatment of Hodgkin's disease].
AB  - In recent years, continuous optimization of therapy has decisively improved the
      prognosis of Hodgkin's disease. However, this improvement in overall survival has
      also led to an increase in several possible late effects which the clinician must
      be aware of. Due to the appearance of chronic fatigue symptoms, cardiopulmonary
      problems, hypothyreosis and damage to the gonadal system including azoospermia
      and ovarian insufficiency, the mostly young patients often suffer a persistent
      reduction in quality of life. In addition, the increased incidence of second
      malignancies following successful primary treatment presents a considerable
      problem. While complete remission and prolonged survival were previously the main
      objectives in the therapy of malignant lymphomas, reduction or avoidance of
      toxicity is now becoming more and more central. This development has led to the
      increasing importance of late sequelae and quality of life as endpoints in modern
      therapy trials in oncology.

PMID- 10943099
TI  - [Lowered intrarenal protein degradation--an alternative path to
      glomerulosclerosis and tubulo-interstitial fibrosis].
AB  - Chronic renal failure is the consequence of progressive glomerulosclerosis and
      tubulo-interstitial fibrosis. The initiating hallmark of nephrosclerosis
      represents nephronal hypertrophy, due to an accumulation of proteins in the
      glomeruli and tubulointerstitium. From experimental and clinical investigations
      the conclusion can be drawn that the disturbed intrarenal protein balance with
      the consequent nephronal hypertrophy is at least partly the result of reduced
      protein degradation. Potential factors involved in impaired renal proteinase
      activities are cytokines like transforming growth factor beta 1 (TGF-beta 1),
      angiotensin II and advanced glycation endproducts (AGEs). CONCLUSION:
      Nephrosclerosis as the common histological endpoint of chronic renal
      insufficiency is the result of an interaction between many pathogenetic factors.
      Its growing understanding implies the possibility of new therapeutic options to
      retard the progressive course of chronic renal failure.

PMID- 10943100
TI  - [Imported viral infections in international travel; from the virtual to real
      epidemiology of pandemics].
AB  - Viruses have become more mobile alongside with increasing human mobility and
      speed of travel. At the same time we get access to information on viral outbreaks
      and epidemics from large parts of the world faster than ever before. Two recent
      epidemics will be presented to explore the value and the consequences of
      communicating epidemiological information through the Internet. The epidemiology,
      clinical features, diagnostic procedures and prophylaxis of imported viral
      infections are presented. Risk factors for the emergence and resurgence of viral
      diseases are being discussed.

PMID- 10943101
TI  - [Progressive dyspnea, angina pectoris and weight loss in a 76-year old patient].
AB  - BACKGROUND: Cardiac metastases are a rare finding. The primary diagnosis of a
      malignant disease by cardial metastases is a curiosity. CASE REPORT: A 76-year
      old patient presented with dyspnea, angina pectoris and body weight loss.
      Echocardiography showed a circular pericardial effusion and intramyocardial
      masses with high echodensity in the right atrial and the right ventricular wall.
      MIR was not diagnostic of the intramyocardial masses. The pericardiocentesis was
      negative. The procedures revealed an intestinal type gastric adenocarcinoma.
      CONCLUSION: Echocardiography is an established method for the diagnosis of
      cardiac metastases.

PMID- 10943102
TI  - [Bone marrow granulomatosis in Q-fever].
AB  - BACKGROUND: Petersdorf and Beeson defined Fever of Unknown Origin (FUO) as an
      illness characterized by rectal temperature exceeding 38.3 degrees C on at least
      3 occasions, evolving during at least 3 weeks, with no diagnosis reached after 1
      week of in-patient investigation. A quarter of FUO cases is caused by infectious
      diseases, most often hidden abscesses, subacute endocarditis and tuberculosis.
      CASE REPORT: In a 29-year-old patient with undulating fever of 3 months duration
      solely the demonstration of bone marrow fibrin ring granulomas led to the
      diagnosis of protracted Q-fever. The diagnosis later has been proved by elevated
      Coxiella burnetii antibody titers. CONCLUSION: The case report underlines the
      diagnostic value of bone marrow biopsy in the evaluation of fever of unknown
      origin.

PMID- 10943103
TI  - [Acute mesenterial artery occlusion--an unusual symptom of primary
      antiphospholipid antibody syndrome].
AB  - BACKGROUND: The antiphospholipid-antibody syndrome (APS) is a thrombophilic
      disorder, in which venous and arterial thrombosis can occur. We report the rare
      case of a patient with mesenteric infarction due to primary APS. CASE REPORT: A
      46-year-old male patient was admitted to the hospital because of severe abdominal
      pain. A laparotomy was performed and revealed infarction of a jejunal loop which
      was resected. At pathohistological examination mesenteric artery infarction was
      found. Preoperatively prolonged partial thromboplastin time led to coagulation
      analysis. Lupus anticoagulant and anticardiolipin antibodies were found.
      TREATMENT: The diagnosis of primary APS was made and the patient was treated with
      aspirin (100 mg/day) and low molecular weight heparin (2,500 IE/day) permanently.
      Eighteen months after mesenteric infarction the patient is free of further
      thromboembolic events.

PMID- 10943104
TI  - [Dyspnea and abdominal pain in a woman with pericardial tumor: a rare
      complication of the Noonan syndrome].

PMID- 10943105
TI  - Births, marriages, divorces, and deaths: provisional data for September 1999.

PMID- 10943106
TI  - [Incidence and distribution of t(12;21) in prognostic groups of pediatric acute
      lymphoblastic leukemia].
AB  - The authors investigated by reverse transcription-polymerase chain reaction the
      incidence of the t(12;21)(p13;q22) translocation among 130 pediatric acute
      lymphoblastic leukemia registered by the Hungarian Pediatric Oncology Workgroup.
      The distribution of this translocation was analysed in the ploidy categories as
      defined by the flow cytometric DNA analysis and interphase cytogenetics. The
      incidence of the translocation proved to 19%, the positive patients' age ranged
      between 2 and 14 with an average of 5.8 years. Ninety percent of the leukemic
      patients harbouring the t(12;21) exhibited the precursor B-cell phenotype, 10%
      coexpressed myeloid markers. Coexistence of the t(12;21) with the m-bcr type of
      Philadelphia translocation was not observed. Ninety five percent of the t(12;21)
      positive children was diploid by flow cytometry whereas the same figure proved to
      be 58% using interphase cytogenetics. This difference was due to the hypo- and
      pseudodiploidy undetectable by flow cytometry but revealed by interphase
      cytogenetics. The authors conclude that the t(12;21) positive patients which
      seemed to be homogeneous at gross DNA level were markedly heterogeneous with
      interphase cytogenetics and this might explain the inconsistent data in the
      literature in connection with prognostic significance of the t(12;21).

PMID- 10943107
TI  - [The effects of statins on stroke and cardiovascular incidence in randomized,
      placebo-controlled trials with clinical endpoints].
AB  - In the mortality statistics behind the coronary heart disease and cancer the
      stroke is the third leading cause of death. The risk factors of stroke and
      coronary heart disease are similar, but in a recent meta-analysis (Prospective
      Studies Collaboration) on 450,000 patients from 45 studies didn't find close
      correlation between the occurrence of stroke and the cholesterol level. In the
      Multiple Risk Factor Intervention Trial the incidence of haemorrhagic and non
      haemorrhagic stroke was analysed separately and a significant correlation has
      been found between the high cholesterol level and occurrence of the non
      haemorrhagic stroke. The great statin trials in a large scale of patients' groups
      (different cholesterol and risk levels at the inclusion) beside the decline of
      coronary events proved a decrease in stroke incidence too. The mechanism of
      action of the statins on stroke is not known: beside the cholesterol lowering
      effect the so called pleiotropic effects (plaque stabilisation, improvement of
      endothelial dysfunction and antithrombotic properties) and a direct effect on
      vascular tone could get importance. The fact that statins could improve the
      incidence of coronary events with 24-34%, that of stroke with 10-31%, suggests,
      that this drugs has to be used more frequently in the clinical practice.

PMID- 10943108
TI  - [Symptoms of fungal esophagitis in alcoholic liver disease].
AB  - Symptoms related to fungal esophagitis were studied in patients with alcoholic
      liver disease who underwent upper gastrointestinal endoscopy. Data of 517
      patients were studied retrospectively (group I) and 100 alcoholic liver disease
      patients, that were successively admitted to hospital, were enrolled in the
      prospective part (group II). Out of the 41 cases with fungal esophagitis found in
      group I, data of 38 could be evaluated. In group II 13 of the 93 evaluable
      patients had fungal esophagitis; according to Kodsi's grading 10 patients had
      grade 1., one patient grade 2. and two patients grade 2-3. oesophagitis. There
      was no case with grade 4. esophagitis. The rate of symptoms among the 51 patients
      with fungal esophagitis was: anorexia 23 (45.0%), abdominal pain 22 (43.1%),
      vomiting 17 (33.3%), nausea 15 (29.4%), occult gastrointestinal bleeding 12
      (23.5%), weight loss 9 (17.6%), melena 7 (13.7%), bloating 6 (11.7%), acidic
      regurgitation 3 (5.8%), haematemesis 2 (3.9%), thoracic pain 2 (3.9%), singultus
      1 (1.9%), odynophagia 0 and dysphagia 0. In 7 patients (13.7%) none of the
      studied symptoms could be identified. Despite the relatively high frequency of
      symptom free fungal esophagitis reported in the literature, the total lack of
      odynophagia and dysphagia in our patient group was remarkable. In the lack of
      deglutition disorders the other symptoms do not raise the suspicion of
      esophagitis. The diagnosis in such cases can be established only by endoscopy.

PMID- 10943109
TI  - [Potentials of screening for Chlamydia trachomatis in Hungary: cost-benefit
      analysis].
AB  - Untreated chlamydial infections of the genital tract may cause a wide range of
      serious complications, which could be prevented by screening. Cost-effectiveness
      analysis based on previously reported epidemiological study among pregnant women
      was carried out to develop and evaluate cost-effectiveness of age-based screening
      (women younger than 20 years old) for Chlamydia trachomatis in Hungary. Three
      kind of screening strategies were used: a) no screening, b) screening by using
      ELISA test and c) screening by amplified Gen-Probe diagnostic test. Young age and
      unmarried status were significant predictors of the chlamydial infection.
      Prevalence of chlamydial infection was 11.4% in the group of age younger then 20
      years. Strategy b) was more cost-effective than neither testing nor treating.
      Strategy c) was less cost-effective than non screening, unless certain conditions
      were satisfied. If the cost of the diagnostic test were less or equal than 2,000
      HUF or the prevalence of infection in women were greater than 17%, screening
      strategy c) would be more cost-effective than no screening. Although screening by
      using ELISA test was more cost-effective than screening by amplified Gen-Probe
      test, additionally 10,000 infected cases could be prevented using amplified Gen
      Probe method for screening Chlamydia trachomatis.

PMID- 10943111
TI  - [Minimally invasive gallbladder surgery].

PMID- 10943110
TI  - [Impending paradoxical embolism].
AB  - The case history of a 49-year-old female patient is reported, who was operated on
      because of varicose vein in the left lower extremity. A few days after the
      operation serious signs of cerebrovascular insult appeared. The clinical picture
      and the result of an urgent transoesophageal echocardiography are described; a
      serpentine thrombus was found to be trapped in the patent foramen ovale. During
      continuous intravenous heparin treatment, the patient gradually recovered, but a
      residual neurological deficit could be detected on discharge from the hospital.
      Six days after the admission, repeated transoesophageal echocardiographic
      examination showed no signs of intracardiac thrombus. The clinical feature of the
      illness, the predisposing factors, the diagnostic and therapeutic possibilities
      are discussed.

PMID- 10943112
TI  - [Minimally invasive gallbladder surgery].

PMID- 10943113
TI  - Neuroepithelial 'compartments' and the specification of vestibular projections.
AB  - The implication that there exist coherent vestibulo-ocular neuron pools with
      specific functions may provide new insight into how conjugate eye movements are
      synthesized within the vestibulo-ocular reflex. The systematic relationship
      between pool position and synergistic principle terminations, the 'hodological
      mosaic' suggests, moreover, a determinate groundplan established by developmental
      mechanisms operative at early stages in the hindbrain neuroepithelium. From such
      a groundplan, evolutionary and use-dependent modifications could mold
      connectivity patterns functionally appropriate for each species and individual.
      How the expression of developmentally regulatory genes contributes to
      establishing the mosaic organization of the vestibular system is the current
      focus of our research.

PMID- 10943114
TI  - Antero-posterior boundaries and compartments in the cerebellum: evidence from
      selected neurological mutants.

PMID- 10943116
TI  - Lineage, development and morphogenesis of cerebellar interneurons.

PMID- 10943115
TI  - Climbing fiber synapse elimination during postnatal cerebellar development
      requires signal transduction involving G alpha q and phospholipase C beta 4.

PMID- 10943117
TI  - Transgenic methods for directing gene expression to specific neuronal types:
      cerebellar granule cells.

PMID- 10943118
TI  - The function of cerebellar Golgi cells revisited.

PMID- 10943119
TI  - Precise spike timing of tactile-evoked cerebellar Golgi cell responses: a
      reflection of combined mossy fiber and parallel fiber activation?

PMID- 10943120
TI  - Unravelling cerebellar circuitry: an optical imaging study.

PMID- 10943121
TI  - Electrotonic coupling synchronizes interneuron activity in the cerebellar cortex.

PMID- 10943122
TI  - Unipolar brush cells of the vestibulocerebellum: afferents and targets.

PMID- 10943123
TI  - Topography of cerebellar nuclear projections to the brain stem in the rat.
AB  - The organization of the cerebellum is characterized by a number of parallel and
      parasagittally ordered olivocorticonuclear modules; as such, the cerebellar
      nuclei basically function as output system of these modules. The present study
      provides a comprehensive and detailed description of the organization of the
      connections from the cerebellar nuclei to the brain stem in the rat. Thirteen
      small injections with the anterograde tracer Phaseolus vulgaris leucoagglutinin
      or biotinylated dextran amine which were centered on various aspects of the
      cerebellar nuclear complex are described and are illustrated with serial plots
      detailing the distribution of labeled varicosities throughout the brain stem. In
      every case at least 1,000 an up to 36,000 varicosities were plotted. All
      injections resulted in some or heavy labeling concentrated within specific
      regions of the contralateral inferior olivary complex and, usually, in some
      labeling of the contralateral ventrolateral thalamus. However, apart from these
      two areas it is shown that the cerebellar projections are generally very
      widespread and may be found throughout the entire brain stem. Below, only a
      survey of main projection areas will be given. Terminal arborizations originating
      from the rostral part of the medial cerebellar nucleus are mostly found in the
      caudal half of the brain stem with emphasis on the vestibular nuclear complex,
      whereas its caudal part rather connects to midbrain areas. Terminals that
      originate from the dorsolateral protuberance of the medial cerebellar nucleus are
      distributed more evenly throughout the brain stem and are mostly confined to
      reticular areas. The interstitial cell groups, interspersed between the medial
      and both interposed cerebellar nuclei, provide major projections to the
      ipsilateral vestibular nuclear complex and contralateral mesodiencephalic
      regions. However, reticular areas are also targeted over a large rostrocaudal
      range. The medial part of the posterior interposed nucleus sends most projections
      to the caudomedial red nucleus, prerubral regions and parvicellular reticular
      formation, all contralateral to the injection site. Projections that originate
      from more laterally placed injections are directed, apart from the inferior
      olivary complex, to the rostral half of the contralateral brain stem, where most
      labeled varicosities are found in the superior colliculus and zona incerta. The
      anterior interposed nucleus specifically targets the inferior olive, the red
      nucleus, the pontine reticulotegmental nucleus, the prectectum and the
      ventrolateral thalamic nucleus. More laterally placed injections also project to
      the ipsilateral parvicellular reticular formation and deep layers of the spinal
      trigeminal complex. The latter areas are more specifically targeted by the
      dorsolateral hump. In addition, its projections are found in the red nucleus and
      pretectum but do not seem to reach the ventrolateral thalamus. Projections from
      the lateral cerebellar nucleus are all characterized by a widespread distribution
      of terminals. Especially, the caudal aspect of the nucleus sends, apart from
      projections to the deep mesencephalic nucleus, red nucleus, periaquaductal gray,
      pretectum, prerubral area, and several thalamic regions, prominent projections to
      the caudal brain stem which terminate in the inferior olive and gigantocellular
      reticular formation. Projections from the ventral, parvicellular part of the
      nucleus are mostly, but not exclusively, directed to the rostral half of the
      brain stem and mainly terminate in the pararubral area, accessory oculomotor
      nuclei, pretectal areas, zona incerta, and in the parafascicular and
      ventrolateral thalamic nuclei. We conclude that the impact of the cerebellar
      nuclei on the brain stem is widespread; projections from different regions of the
      same cerebellar nucleus may show important differences in distribution of labeled
      terminals. On the other hand, injections placed in different cerebellar nuclei
      may result in a simila

PMID- 10943124
TI  - The entire trajectory of single climbing and mossy fibers in the cerebellar
      nuclei and cortex.
AB  - The present study has revealed that OC axons gave rise to a number of thin
      collaterals. Due to the abundance of these non-CF thin collaterals, it seems
      better to make a distinction between the terms CFs and OC axons, as was done in
      the present paper. The present findings on the innervation of PC dendrites by CFs
      are basically similar to those in previous reports (Ramon y Cajal, 1911; Palay
      and Chan-Palay, 1974). The number of swellings on a single CF in the present
      study (n = 250) is comparable to a previously measured value in the rat (n = 288;
      Rossi et al., 1993) and larger than a value in the frog (n = about 100 beads;
      Llinas et al., 1969). The average number of CFs per OC axon in this study was
      close to the number (n = about 7) inferred in the rat by counting the total
      number of IO neurons and PCs (Schild, 1970). Contact of interneurons by some
      swellings of CFs in the molecular layer was emphasized by Scheibel and Scheibel
      (1954) in their study with Golgi staining. Despite the contact of CF terminals on
      interneurons, the formation of a synaptic structure between them has been
      excluded in an electron-microscopic study (Hamori and Szentaothai, 1980). On the
      other hand, electrophysiological studies have demonstrated a weak excitatory
      effect of CFs on some interneurons (Eccles et al., 1966). Terminals in the
      granular layer were originated either from thin collaterals of OC axons or from
      retrograde collaterals of CF terminal arborizations. The former was the main
      source of swellings in the granular layer. The morphology of the thin collaterals
      in the present study was consistent with "globose varicosities connected by a
      fine thread" as described in Golgi preparations and electron micrograms (Chan
      Palay and Palay, 1971). Swellings of thin collaterals (about 1.7% of the total
      number of swellings per OC axon) were most abundant in the upper portion of the
      granular layer just underneath the PC layer, in which Golgi cells are usually
      located. Furthermore, some of these swellings were observed to touch presumed
      Golgi cells in the present study, which is consistent with electron-microscopic
      findings on the innervation of somata of Golgi cells by thin collaterals (Hamori
      and Szentaothai, 1980; Chan-Palay and Palay, 1971). Inferior olive stimulation
      has been shown electrophysiologically to have a weak direct excitatory effect on
      Golgi cells (Eccles et al., 1966). Ninety-one percent of the OC axons examined
      had nuclear collaterals; since the possibility of insufficient staining could not
      be excluded, this percentage may be an underestimation. The ratio of swellings in
      the cerebellar nuclei versus those of CF terminal arborizations was about 0.036
      in individual OC axons in the present study. However, since the volume of the
      cerebellar nuclei is much smaller than that of the cerebellar cortex, and
      significant convergence of input from OC axons to cerebellar nucleus neurons is
      present (Sugihara et al., 1996), cerebellar nucleus projection of OC fibers can
      still be functionally important. Some swellings seemed to make contact with the
      soma and the proximal portions of dendrites of large neurons in the present
      study, which is consistent with the steep rising phase of postsynaptic excitatory
      potentials in cerebellar nucleus neurons following IO stimulation (Kitai et al.,
      1977; Shinoda et al., 1987). Although intracellular potentials were presumably
      recorded only from large output neurons in the cerebellar nuclei, the present
      study suggested that small neurons were also innervated by OC axons. The present
      study revealed that virtually all reconstructed LRN axons projected not only to
      the Cx as mossy fibers, but also to the DCN including the VN by their axon
      collaterals. None of the LRN neurons specifically projected to the DCN without
      projecting to the Cx, namely all axon terminals of LRN neurons in the DCN and VN
      belonged to axon collaterals of mossy fibers projecting to the Cx. (ABSTRACT
      TRUNCATED)

PMID- 10943125
TI  - Micro-organisation of cerebellar modules controlling forelimb movements.

PMID- 10943126
TI  - Gating of climbing fibre input to cerebellar cortical zones.

PMID- 10943127
TI  - GABAergic modulation of olivary oscillations.

PMID- 10943128
TI  - Analysis of the discharge pattern of floccular Purkinje cells in relation to
      vertical head and eye movement in the squirrel monkey.
AB  - Purkinje (P) neurons are highly irregular in their discharge patterns having a
      high coefficient of variation. We have developed a method to extract the signal
      from these noisy neurons employing multiple linear regression against the input
      signals that are causal in P-cell firing, namely retinal slip, head motion
      parameters, and the efference copy of the oculomotor commands. This method was
      shown to extract all of the experimental stimulus-related signal as the residual
      following extraction had the same amplitude distribution and spectral content as
      those of the spontaneous discharge of P-cells when no external stimuli were
      applied. The method enables us to decompose P-cell firing modulation into
      components mediated by mossy fiber inputs to flocculus, that is, retinal slip,
      vestibular and oculomotor efference copy signals. By evaluating these components
      in relation to VOR adaptation, one can argue that one role of the flocculus is in
      converting these sensory and efference copy input signals into eye movement
      related signals in conjunction with VOR motor learning.

PMID- 10943129
TI  - Hypotheses about the neural trigger for plasticity in the circuit for the
      vestibulo-ocular reflex.

PMID- 10943130
TI  - On the nature of gain changes of the optokinetic reflex.

PMID- 10943131
TI  - Use-dependent changes in synaptic strength at the Purkinje cell to deep nuclear
      synapse.

PMID- 10943132
TI  - Time window control: a model for cerebellar function based on synchronization,
      reverberation, and time slicing.
AB  - We present a new hypothesis of cerebellar function that is based on
      synchronization, delayed reverberation, and time windows for triggering spikes.
      Our model suggests that granule cells admit mossy fiber activity to the parallel
      fibers only if the Golgi cells are firing synchronously and if the mossy-fiber
      spikes arrive within short and well-defined time windows. The concept of time
      window control organizes neuronal activity in discrete 'time slices' that can be
      used to discern meaningful information from background noise. In particular,
      Purkinje cell activity can trigger rebound spikes in deep cerebellar nuclei
      cells, which project via brain stem nuclei and mossy fibers back to the
      cerebellar cortex. Using a detailed model of deep cerebellar nuclei cells, we
      demonstrate that the delayed firing of rebound spikes is a robust mechanism so as
      to ensure that the reverberated activity re-arrives in the mossy fibers just
      during the granule-cell time window. Large network simulations reveal that
      synaptic plasticity (LTD and LTP) at the parallel fiber/Purkinje cell synapses
      that relies on the timing of the parallel fiber and climbing fiber activities
      allows the system to learn, store, and recall spatiotemporal patterns of spike
      activity. Climbing fiber spikes function both as teacher and as synchronization
      signals. The temporal characteristics of the climbing fiber activity are due to
      intrinsic oscillatory properties of inferior olivary neurons and to reverberating
      projections between deep cerebellar nuclei, the mesodiencephalic junction, and
      the inferior olive. Thus, the reverberating loops of the mossy fiber system and
      climbing fiber system may interact directly with the time windows provided by the
      circuitry of the cerebellar cortex so as to generate the appropriate spatio
      temporal firing patterns in the deep cerebellar nuclei neurons that control
      premotor systems. In future studies the model will be extended in that high
      frequency simple spike activities will be included and that their relevance for
      motor control will be addressed.

PMID- 10943133
TI  - Electrophysiological behavior of Purkinje cells and motor coordination in
      calretinin knock-out mice.

PMID- 10943134
TI  - Contralateral cerebellar involvement in conditioned eyeblink responses.

PMID- 10943135
TI  - Involvement of the cerebellum in a new temporal property of the conditioned
      eyeblink response.

PMID- 10943136
TI  - [Imaging procedures in the region of neck blood vessels: DSA, MRA, CT
      angiography].

PMID- 10943137
TI  - [Tumors of the anterior skull base. Effects of perioperative imaging on adjuvant
      radiotherapy planning].
AB  - OBJECTIVES: Treatment of anterior skull base tumours is still considered being a
      major challenge for all involved disciplines. Surgical management, complications,
      as well as the role of imaging for multimodality treatment options should be
      evaluated critically. PATIENTS AND METHODS: 57 patients underwent
      interdisciplinary one step trans-basal approaches for resection of benign and
      malignant anterior fossa tumours. Beside assessment of surgical results and
      perioperative morbidity, in 13 patients with malignant tumours perioperative
      imaging was evaluated with regard to further possible radio-oncological treatment
      options. RESULTS: Applying trans-basal approaches radical tumour resection could
      be achieved in all cases independent of tumor-size (diameter 12-114 mm).
      Permanent postoperative complications (until 6 months postoperatively) were found
      in 4 cases (7%), transient complications in 7 cases (12.3%). Evaluation of
      perioperative imaging showed a heterogen use of different imaging modalities and
      revealed lack of standardization, hampering further planning of radiation
      therapy. CONCLUSION: Treatment of anterior skull base tumours requires a maximum
      level of standardization of perioperative imaging, to grant a successful surgical
      and radio-oncological interdisciplinary patient management.

PMID- 10943138
TI  - [Dynamic magnetic resonance tomography (MRI): a follow-up study after femur core
      decompression and instillation of recombinant human bone morphogenetic protein-2
      (rhBMP-2) in avascular femur head necrosis].
AB  - OBJECT: The aim of the study was to test the use of dynamic magnetic resonance
      imaging study with Gd-DTPA-application and the dynamic changes of signal
      intensity at patients with avascular femoral head necrosis after having installed
      rhBMP-2 and/or decompressed the core. MATERIAL AND METHODS: Six patients with
      avascular necrosis of the femoral head ARCO-stage I- or II-lesions were treated
      surgically by femoral head core decompression. Three of these patients were
      additionally treated with rhBMP-2-instillation. The progression or regression
      could be confirmed by T1- and T2-weighted spinecho-sequences (zero, four, ten,
      sixteen weeks and 24 months follow up). RESULTS: Corresponding ARCO
      classification with partly more sensitive measurement of vitality signs in
      comparison to the optical x-ray classification. The objective, quantitative
      measurement of signal intensity post contrast medium reduces the influence of
      experience and level of education. The dynamic sequences results are
      reproducible. CONCLUSION: The dynamic magnetic resonance imaging study after Gd
      DTPA-application and the dynamic changes of signal intensity after Gd-DTPA
      enhancement in the necrotic areas of the femoral head were the important subject
      of our study and it seems, that these sequencies and the ascertainment of signal
      intensity changes will be an efficient method for judgement of vitality,
      vascularisation and perfusion after therapeutical intervention. Combination of
      femoral head core decompression and rhBMP-2-instillation for the purpose of
      osseous regeneration seems to stabilize the affection.

PMID- 10943139
TI  - [Reversible cyclosporin A-induced leukoencephalopathy: a case report and
      differential diagnosis discussion].
AB  - The pathogenesis of Cyclosporin A (CsA) induced toxic leukoencephalopathy is
      unclear. CCT and CMRI reveal hypodense respectively hyperintense bilateral and
      symmetrical changes predominantly in the posterior white matter. We report a
      patient with a severe CsA induced toxic leukoencephalopathy in whom clinical
      symptoms (complete loss of brainstem functions, coma) and morphological changes
      in CCT and CMRI were completely reversible after immunosuppression with CsA has
      been stopped. We furthermore discuss the differential diagnoses of CCT and CMRI
      findings.

PMID- 10943140
TI  - [Use of the ROC method in image quality problems in roentgen mammography. I. ROC
      analysis as image quality test procedure].

PMID- 10943141
TI  - . . . The greatest of these is charity.

PMID- 10943142
TI  - Confusion in the ranks.

PMID- 10943143
TI  - Doctors "give back" to make their communities ... and their world ... a better
      place.

PMID- 10943144
TI  - Health care serious business for coalitions. Groups make a difference in
      community health care delivery.

PMID- 10943145
TI  - Loss prevention case of the month. Would it have affected the outcome?

PMID- 10943146
TI  - New program development in academic medical centers: the story of geriatrics in
      Tennessee.

PMID- 10943147
TI  - An autonomy supportive model of geriatric team function.
AB  - Interdisciplinary teams play a critical role in the delivery of geriatric health
      care. Health care professionals are commonly left to develop teamwork skills by
      chance. Medical team function differs from traditional group theory in that all
      members are caregivers. A non-competitive supportive atmosphere is appropriate
      for patient care. We propose a participatory (autonomy supportive) model
      fostering self-realization and positive reinforcement as an organizing
      philosophy. The primary group task is to maximize patient functional independence
      and personal goals. Leadership is task-dependent.

PMID- 10943148
TI  - Reporting deaths to the medical examiner.

PMID- 10943149
TI  - Vanderbilt morning report. Idiopathic polymyositis as the initial manifestation
      of lupus erythematosus.

PMID- 10943150
TI  - [Clinical manifestations and diagnosis of childhood mediastinal tumors].
AB  - Mediastinal tumors make up as high as 7% of the malignant neoplasms in children
      and are encountered in all age groups, slightly more commonly in preschool
      children. Three main groups of common symptoms that are typical of mediastinal
      tumors are identified. These include 1) symptoms associated with tumor
      compression of thoracic organs; 2) neurological disorders associated with
      compression or destruction of ganglionary nodes; 3) general symptoms. Posterior
      mediastinal tumors are diagnosed by X-ray in 85% of cases. X-ray computed
      tomography makes it possible to judge of the initial site of a neoplasm, the
      presence of inclusions, the status of adjacent organs and tissues, the density of
      a pathological focus. Gallium-67 citrate radionuclide study allows one to make an
      early differential diagnosis between a solid formation and lymph proliferative
      disease. The lack of morphological verification of a diagnosis requires the use
      of transthoracic aspiration biopsy whose diagnostic value enhances when it is
      made under guidance of ultrasound or X-ray computed tomography.

PMID- 10943152
TI  - [Diagnosis and treatment of large-cell anaplastic lymphoma in children].
AB  - Thirty eight children with large-cell anaplastic lymphomas have been recently
      treated at the Pediatric Department of Malignant Lymphomas, Russian Cancer
      Research Center, Russian Academy of Medical Sciences. Cytoimmunological studies
      have revealed that 24 patients had 4 types of cellular elements of large-cell
      anaplastic lymphoma: Kil(+), Kil(+)B, B-cell, and T-cell lymphomas in 11, 2, 8,
      and 3 children, respectively. Intensive chemotherapy was performed in relation to
      the immunophenotype.

PMID- 10943151
TI  - [Diagnosis of germinogenic ovarian tumors in girls].
AB  - The paper covers the problems of diagnosis of germinogenic ovarian tumors in
      girls, which make up as high as 80% of all malignant ovarian tumors. For timely
      diagnosis, it is necessary to take into account clinical data, the levels of
      tumor markers (alpha-fetoprotein, chorionic gonadotropin) and ultrasound
      findings. This all is rather sufficient to verify the diagnosis of ovarian tumor
      lesions. Other additional studies are aimed at establishing where the process
      extends.

PMID- 10943153
TI  - [Ultrasound tomography in diagnosis of malignant soft tissue tumors in children].
AB  - Ultrasound findings of 50 children with soft tissue sarcomas of the trunk and
      limbs were analyzed. There was a high proportion of diagnostic errors (62%),
      which resulted in the choice of adequate therapeutical measures at early stages
      of therapy and in advanced disease. The reasons of the errors were as follows:
      nonspecificity of the first clinical manifestations of soft tissue sarcomas;
      ignorance of instrumental studies that establishes a diagnosis in time;
      outpatient physicians' unconcern of cancer, misunderstanding of the nontumor
      nature of disease; no scientifically grounded algorithm of studies. Echographic
      signs that characterize malignancy, their changes over a therapy, ultrasound
      pattern due to posttherapeutical changes are considered.

PMID- 10943154
TI  - [Organ-preserving surgical interventions in unilateral nephroblastomas in
      children].
AB  - The paper presents data available in the literature and the authors' own findings
      of organ-preserving treatment of 9 children with unilateral nephroblastoma. It
      proposes absolute and relative indications for organ-preserving treatment in this
      pathology.

PMID- 10943155
TI  - [Study of tumor cells sensitivity in patients with acute leukemia to cytokines
      and their combined use with drugs in vitro by MTT analysis].
AB  - MTT analysis has yielded data on the sensitivity of leukemia cells isolated from
      64 patients with acute leukemia to the cytokines G-KSF?, GM-KSF, interferon-alpha
      2b and their combined use with drugs, such as cytosar, vepeside, doxorubicin,
      vincrastine, L-asparaginase. The mean in vitro survival of leukemia cells in
      children with acute lymphoblast cell leukemia (ALCL) was 1.9 times less than that
      in acute myeloblast cell leukemia (AMCL) (p < 0.001), that in new cases of ALL
      was 2.3 times less than in relapses (p = 0.024). The stimulating effect of GM-KSF
      on the survival rates of leukemia cells was seen in 64.7% of patients with AML.
      That of GM-KSF was recorded in 21.4% of cases. The survival of lymphoblast cells
      isolated from children with ALL did not differ greatly in the absolute majority
      of cases (by more than 30%) in the presence of growth factor in the medium. The
      cytotoxicity of XII with medium growth factor decreased in most cases. However,
      some cases (more frequently in AML than ALCL) displayed a higher cytotoxicity of
      XII, particularly cytosar in the presence of G-KSF and GM-KSFG; LC50 of Ara-C
      decreased by 30% or more in the presence of growth factor in 36% of patients.
      Incubation with interferon alpha 2b caused a reduction in the survival of
      leukemia cells, which was more pronounced in children with ALL. Interferon-alpha
      2b caused an increase in the cytotoxic effect of XII on leukemia cells in ALL to
      a greater extent; cytosar, vepeside, and doxorubicin enhanced the effect by 1.47,
      1.39, and 2.35 times, respectively.

PMID- 10943156
TI  - [Use of subgrafting doses of peripheral stem cells is a new approach to
      overcoming hematological toxicity of multiple intensive courses of chemotherapy
      in children].
AB  - The authors examined 8 patients with pretreated relapsing or resistant solid
      tumors (Wilms'--4, rhabdomyosarcoma--3, synovial sarcoma--1) who received 16
      courses of chemotherapy: iphosphamide, 1800 mg/m2/day (days 1-5), vepeside, 100
      mg/m2/day (days 1-5), and carboplatin 500 mg/m2/day (day 1) (IVC) and 18 courses
      of therapy wherein iphosphamide was replaced by cyclophosphanum, 400 mg/m2/day
      (days 1-5) (CVC). The patients received 2-4 induction courses (n = 18) and 1-5
      consolidation courses (n = 16) with reinfusion of peripheral stem cells (PSC).
      All PSC separations were performed after the first or second courses of IVC/CVE.
      There were no significant increases in the duration of leukopenia and
      thrombocytopenia, in the incidence of infection with a higher ordinal of a course
      performed by PSC maintenance. The findings suggest that the small doses of PSC
      stimulated by colony-stimulating factor can maintain hemopoiesis and decrease the
      rate of the estimated bone marrow depletion long after repeated courses of
      chemotherapy in patients with prognostically poor solid tumors.

PMID- 10943157
TI  - [Low-intensity lasers in pediatric oncology].
AB  - The paper outlines the outcomes of treatment for complications associated with
      chemo- and radiation therapy in children with malignant neoplasms by using low
      intensity laser radiation. The use of this therapy may reduce the duration of
      treatment of these complications by 1.5-2 times. The use of low-intensity laser
      radiation in the treatment of other complications that are common in pediatric
      oncological care is briefly described.

PMID- 10943158
TI  - [Evaluation of accelerography in use of muscular relaxants in children with
      oncological pathology].
AB  - The paper presents the results of study of neuromuscular conduction and
      neuromuscular block by accelerography (TOF) in 100 children operated on for
      abdominal, retroabdominal, and mediastinal tumors. The currently available
      myorelaxants Arduan, Tracrium, and Mivacron are studied. There is evidence for
      the high informative and prognostic values of accelerography, in infusion of
      drugs in particular, which makes it possible to lower the total dose of muscular
      relaxants, to avoid decurarization, and to change myoplegia policy in accordance
      with the intraoperative situation.

PMID- 10943159
TI  - [Epidermal growth factor receptors in malignant and benign tumors in children].
AB  - The radioligand technique was used to study the amount of epidermal growth factor
      receptors (EGFR) in malignant and benign tumors in 32 children aged 8 months to
      17 years. The membranous fraction of 11 of the 32 tumors studied showed EGFR
      equal to 10.1 to 1327 fmol/mg (163.0 +/- 117.5 fmol/mg, median 38.0 fmol/mg). The
      greatest amount of EGFR was found in breast fibroadenomas. There was no clear
      relationship of the frequency and level of EGFR expression to a nosological tumor
      entity in children. A possible role of the EGFR system in tumors in children is
      discussed.

PMID- 10943160
TI  - [Tyrosine metabolism, antioxidative system and free radical lipid oxidative
      processes in children with pigmented nevus and melanoma].
AB  - The plasma levels of tyrosine and the lipid peroxidation intermediate malonic
      dialdehyde (MDA) were measured in children with pigmental nevus and melanoma.
      They were found to have antioxidative protective failure. The presence of
      pigmental nevus predetermines the high incidence of tyrosine metabolic
      abnormalities. In children with pigmental nevus and melanoma, there was an
      impairment in the correlation of the parameters of tyrosine metabolism, the rate
      of free radical lipid peroxidation processes, and the status of the antioxidative
      system. The findings suggest that children with pigmental nevus may be referred
      to as a high cancer risk group and monitoring of these parameters should be
      recommended at follow-up of pigmental nevi.

PMID- 10943161
TI  - [Some indices of gastrointestinal tract status in children cured fro malignant
      neoplasms].
AB  - A total of 2255 individuals who cured from oncological diseases in childhood in
      Moscow in 1978 to 1997 have been studied. Most (60%) children undergone special
      treatment have serious visceral abnormalities. The authors examined the negative
      impact of a special treatment on the gastrointestinal mucosa and changes in its
      function after termination of special therapy in 79 cured patients. The most
      common diagnosed abnormalities included biliary dyskinesis (17-20%),
      dysbacterioris (16%), gastritis (7%). No abnormal gastrointestinal changes were
      detected in 37%.

PMID- 10943162
TI  - [Specific features of stem cell (CD34+) subvariant of acute lymphoblast cell
      leukemia in children].
AB  - The authors have examined 134 children with acute lymphoblast cell leukemia
      (ALCL) who were treated at the Research Institute of Pediatric Oncology and
      Hematology, Russian Cancer Research Center, in January 1990 to November 1999, and
      followed up till March 1, 1999. The mean duration of follow-ups was 57.46 +/-
      2.87 months. The minimum follow-up was 4 months. The immunophenotypical features
      of stem cell immunological subvariant of ALCL identified from the presence of 10%
      or 15% of CD34+ lymphoblast cells were similar in the leukemia clone. There is
      evidence for the isolation of the least mature, stem-cell immunological
      subvariant of ALCL in children. The immunophenotypic features of stem-cell ALCL
      in children were as follows: the expression of myeloid antigens (linear and
      different marker leukemias) and the higher rates of involvement of B-cell
      leukemias. The clinical and hematological features of stem-cell versus CD34
      negative ALCL in children were the low levels of leukocytes (p = 0.009) and blast
      cells (p = 0.018) in the peripheral blood at diagnosis. At the same time, stem
      cell ALCL showed a poorer prognosis. Moreover, blast cell CD34 antigen expression
      deteriorated prognosis for pre-pre-B (common) immunological variant of ALCL (p =
      0.035). Intensified ALCL treatment programmes improved relapseless survival of
      patients with stem-cell ALCL (p = 0.0042).

PMID- 10943163
TI  - [Ways of antioxidative prevention of complications in immediate postoperative
      period in children with nephroblastoma].
AB  - The parameters of the activity of the antioxidative system (AOS) were studied in
      85 patients aged 1 to 14 years who had nephroblastoma in the immediate
      postoperative period. They were compared with those in healthy children. To
      prevent AOS failure, Group 1 patients with nephroblastoma received ascorbic acid
      (AA) in a dose of 15 mg. Group 2 patients took a larger dose (25-30 mg) in
      combination with alpha-tocopherol. It was ascertained that the small dose of AA
      did not prevent AOS failure in the postoperative period while its larger doses
      prevented significant manifestations of antioxidative protective deficit, by
      reducing the incidence and severity of postoperative trophic complications.

PMID- 10943164
TI  - [Sociomedical service in the care system for children with oncological diseases].
AB  - Children with oncological diseases and their families receive no adequate social
      and psychological support, which adversely affects the outcomes of treatment and
      prognosis in patients and in those who have been cured from malignant tumors and
      deteriorates their and their families' life quality. A concept of sociomedical
      measures, which has been worked out at the Research Institute of Pediatric
      Oncology and Hematology, N. Blokhin Russian Cancer Research Center, is built on
      the principle of interdisciplinary approach to providing care to children with
      malignant tumors and it implies the rendering the patient and his or her family
      various social and psychological supports at all stages of specialized care.

PMID- 10943165
TI  - [Current problems of primary and recurrent thyroid cancer treatment].

PMID- 10943166
TI  - Malaria.

PMID- 10943167
TI  - Revision of the International Health Regulations.

PMID- 10943168
TI  - Global Salm-Surv on Internet.

PMID- 10943169
TI  - But is it nursing research?

PMID- 10943170
TI  - Hardships and personal strategies of Vietnam War nurses.
AB  - This study describes hardships faced in Vietnam and personal strategies used to
      deal with these hardships as defined by 24 female military nurses who served
      during the war. Purposive sampling was used, and data were generated using four
      core questions and in-depth interviews. The research methodology was
      phenomenology, incorporating data analysis procedures of Colaizzi, Lincoln and
      Guba, and Van Manen. Eight hardship and nine personal strategy themes were
      identified. This study found that caring for young, severely injured, and
      disfigured soldiers was a significant hardship and that nurses struggled with the
      moral dilemmas inherent in mass casualty situations, triage policies, and the
      practice of returning recovered soldiers to combat. Most nurses relied on
      personally proven and familiar strategies to reduce or buffer the effects of
      emotional hardships, whereas some discovered and used new strategies.

PMID- 10943171
TI  - A feminist critique of breast cancer research among Korean women.
AB  - Studies indicate ethnic differences in incidence, mortality, and survival rate of
      breast cancer. Despite the low incidence rate of breast cancer among the Korean
      population, Koreans are reported to be less likely to survive breast cancer. In
      this article, using a feminist perspective, the reasons why Korean women have
      been reported to be less likely to survive breast cancer are analyzed through a
      critical review of research among Korean women. A total of 469 studies (145
      unpublished master's theses and doctoral dissertations and 324 articles published
      in South Korea and in the United States) were reviewed, analyzed, and critiqued
      in terms of biases present in the research process. Through a feminist critique
      of the literature, four possible reasons are proposed: androcentric views and
      assumptions underlying the research, modesty issues imbedded in Korean culture,
      the victim-blaming tendency of Korean culture, and intense emotions without
      adequate support.

PMID- 10943172
TI  - Severe visual impairment in older women.
AB  - The purpose of this qualitative, phenomenological study was to uncover the
      meaning of severe visual impairment to older women diagnosed with macular
      degeneration, a leading cause of blindness in older adults. The research question
      for the study was, What is the lived experience of severe visual impairment in
      older women diagnosed with macular degeneration? Participants were eight women,
      aged 63 to 85 years, who had been diagnosed with macular degeneration and who had
      severe visual deficits. Data were gathered through audiotaped interviews.
      Interview recordings were transcribed and later analyzed using a modified Giorgi
      methodology. The meaning of severe visual impairment emerged as "persisting
      toward unfolding ways of being in the world sparked by personal discoveries
      amidst enveloping losses while embracing a realistic awareness with steadfast
      positivism." Findings from this study were congruent with the theory of Human
      Becoming. Study findings highlight factors that may place older women with severe
      visual deficits at risk for lower levels of well-being.

PMID- 10943173
TI  - Integrating clinical quality improvement strategies with nursing research.
AB  - Bridging the research-practice gap has been a focus of concern for nursing and
      other health care disciplines. The challenge in linking research and practice is
      for practitioners to use consistently the best available evidence in their
      clinical practice and for researchers to engage in clinically relevant research
      that provides practitioners with the evidence to do so. The authors of this
      article advocate that blending Clinical Quality Improvement (CQI) strategies with
      research methodology is a means of bridging the research-practice gap. The
      process of blending CQI strategies and nursing research is described in this
      article.

PMID- 10943174
TI  - Translation and validation of Caregiving Satisfaction Scale into Korean.
AB  - The purpose of this study was to establish the equivalence and to examine the
      psychometric properties of a Korean translation of the Caregiving Satisfaction
      Scale (CSS). A convenience sample of 44 bilingual Koreans was selected. The
      Cronbach's alpha for the English and Korean versions were .87 and .90,
      respectively. There was significant mean difference between items 3 and 12 of the
      English items and their Korean translations. Pearson's Correlations demonstrated
      that 13 of the 15 CSS items had significant correlations (r = .35-.75, p < .05)
      between two versions. The correlation between total scores of both versions was
      .86 (p < .001). Overall, none of the items would be regarded as having
      unacceptable numeric properties. According to the fine process for translation,
      back-translation, and bilingual field test, the Korean version of the CSS appears
      to have concrete construct validity and reliability for use in measuring
      caregiver satisfaction in the Korean population.

PMID- 10943175
TI  - Job uncertainty and health status for nurses during restructuring of health care
      in Alberta.
AB  - The Alberta health care system experienced dramatic changes after provincial
      funding cuts to health care from 1993 to 1996. As a result, stressors for nurses
      increased. The question of whether job uncertainty, working conditions, cognitive
      appraisal, and coping strategies influence the health of registered nurses in a
      context of health care restructuring was examined. Lazarus and Folkman's
      Transactional Model of Stress was used as the conceptual framework. A total of
      271 registered nurses employed in a large, urban, acute-care teaching hospital
      responded to a self-administered survey questionnaire. Using multiple regression
      analysis, depression and self-reported physical health were analyzed. The data
      suggest that the threat of being placed on recall, having a coworker bumped or
      laid off, and perceived job security were adversely related to physical health.
      High primary appraisal of threat was associated with high levels of depression
      and poor physical health. In addition, the findings suggest that various coping
      strategies had both buffering and exacerbating effects on physical health and
      depression.

PMID- 10943176
TI  - Mailed survey follow-ups--are postcard reminders more cost-effective than second
      questionnaires?
AB  - Finding cost-effective ways to increase response to mailed surveys is a concern
      for many nurse researchers. This study compared two follow-up methods: sending a
      second questionnaire packet versus sending a reminder postcard to those who did
      not respond to an initial mailing. Although the second questionnaire yielded a
      higher response than did the postcard, the cost per additional response was
      approximately 2 1/2 times higher for the questionnaire than for the postcard when
      the differential cost of the two mailings is considered.

PMID- 10943177
TI  - Traumatic dislocation of the hip.

PMID- 10943178
TI  - Description of a dislocation of the head of the femur, complicated with its
      fracture; with remarks by John Birkett (1815-1904). 1869.

PMID- 10943179
TI  - The pathologic features and mechanism of traumatic dislocation of the hip.
AB  - The term traumatic dislocation of the hip encompasses a heterogenous group of
      dislocations, and more commonly, fracture-dislocations which have been
      subclassified. The current study describes the pathologic features in terms of an
      anatomic description of the displaced parts of the joint and what is known of the
      associated injured structures in each of the subtypes. The events that lead to
      traumatic dislocation of the hip are well documented, but understanding of the
      mechanics of the injury can only be presumptive.

PMID- 10943180
TI  - Classification of traumatic hip dislocation.
AB  - The commonly used classification systems of hip dislocation are based on the
      direction of the dislocation and the presence of associated lesions. However, no
      rating system can reliably predict the patient's outcome and prognosis based on
      the initial presentation and classification. In general, patients with anterior
      dislocations have the best prognosis. Other factors affecting the prognosis are
      the associated injuries and more importantly the delay between dislocation and
      reduction.

PMID- 10943181
TI  - Diagnosis and imaging studies of traumatic hip dislocations in the adult.
AB  - Traumatic dislocation of the hip represents a major injury that is associated
      with significant morbidity. In particular, the risk of osteonecrosis of the
      femoral head is greatly affected by the time it takes to reduce the hip.
      Therefore, thorough understanding of the clinical and radiologic features is
      essential if this injury is to be recognized and treated promptly. Most patients
      present in severe distress after a high-energy injury such as a motor vehicle
      accident. Associated injuries, particularly of the knee, are common and the leg
      usually is held in a specific posture characteristic of the direction of
      dislocation. Plain anteroposterior radiographs of the pelvis will clearly show
      the dislocation in most patients but lateral views or a computed tomography scan
      may be required to confirm the diagnosis and to show the direction if the signs
      are subtle. Associated acetabular wall fractures and femoral head fractures also
      may be identified by computed tomography scans. After reduction, plain
      radiographs alone are not adequate to assess reduction; computed tomography is
      more sensitive in detecting osteochondral fragments and may reliably detect
      residual subluxation of 2 mm in any part of the joint. Magnetic resonance imaging
      is useful in detecting changes of osteonecrosis but rarely is indicated in the
      early treatment of this condition.

PMID- 10943182
TI  - Initial treatment of traumatic hip dislocations in the adult.
AB  - The initial treatment of traumatic hip dislocations is critical to successful
      treatment of this injury. It generally is agreed that prompt reduction with the
      patient under anesthesia or sedation is required. Delay in reduction of posterior
      hip dislocations is associated with avascular necrosis of the hip. Occasionally
      the hip dislocation will be irreducible. Various methods to reduce hip
      dislocations have been described in the literature. The superiority of one
      particular technique has not been shown and the choice of reduction maneuver must
      be tailored to the condition of the patient. Traumatic hip dislocations often are
      associated with multiple injuries that may limit the options available for
      initial treatment of the hip dislocation. Adherence to general principles of
      skeletal reduction will increase the ease of reduction and decrease the risk of
      iatrogenic injury during reduction. Additional clinical and radiographic
      evaluation of the hip that was reduced often is necessary to determine whether
      subsequent open treatment is required.

PMID- 10943183
TI  - A review of the treatment of hip dislocations associated with acetabular
      fractures.
AB  - Traumatic dislocation of the hip is an extremely severe injury. Although
      previously considered an uncommon lesion, it now is seen more often as a result
      of motor vehicle accidents. In most cases, dislocation of the hip is associated
      with fractures of the acetabulum, which ultimately can result in a higher
      incidence of complications than the complications observed in pure simple
      dislocations. Early recognition and prompt closed reduction of the dislocated hip
      constitute the cornerstone of proper treatment of this injury. Once the
      dislocation is reduced, definitive treatment of the acetabular fracture can be
      delayed to obtain a precise diagnostic evaluation. If surgical reconstruction of
      the acetabular fracture is indicated, it is done best in the first 10 days after
      the injury. A few patients in whom nonconcentric reduction, failed closed
      reduction, or impaired neurologic status occurs after reduction will require
      early open reduction and internal fixation of the fracture. Complications can be
      caused by the initial injury or by the treatment. Avascular necrosis of the
      femoral head, degenerative osteoarthritis, and heterotopic ossification are the
      main complications encountered in patients with unsatisfactory final results.
      Despite a perfect reduction of the hip dislocation and anatomic reduction of the
      acetabular fracture, a significant degenerative process of the hip is expected
      when the patient is assessed at long-term followup.

PMID- 10943184
TI  - Functional outcome of patients with femoral head fractures associated with hip
      dislocations.
AB  - Fracture of the femoral head after hip dislocation is a relatively rare injury
      often associated with a poor functional outcome. Twenty-six patients who
      sustained femoral head fractures were evaluated using radiographs, clinical
      examinations, and a validated outcome scoring system. The Short Form-12 was used
      to assess functional outcome. Patients whose fractures were stabilized with 3-mm
      cannulated screws and washers had a poor functional outcome. When evaluated with
      an odds ratio analysis, the use of Kocher-Langenbeck posterior approach was
      associated with a 3.2 times higher incidence of the patients having avascular
      necrosis develop when compared with the Smith-Petersen approach. A literature
      review combined with the current series confirms that the principles of early
      reduction of hip dislocation, early stabilization, anatomic reduction of the
      fracture, and rigid fixation are critical principles to attain good results. The
      Brumback classification system provides superior differentiation of different
      fracture types when compared with the Pipkin classification. The Smith-Petersen
      anterior surgical approach is recommended for the majority of patients with
      femoral head fractures. Three-millimeter cannulated screws with threaded washers
      are contraindicated for use in stabilizing femoral head fractures, and should not
      be used in any joint because of dissociation between the screw and the washer.

PMID- 10943185
TI  - Open reduction and internal fixation of posterior wall fractures of the
      acetabulum.
AB  - The results of 94 patients with posterior wall fractures of the acetabulum
      associated with hip instability treated within 3 weeks of injury by open
      reduction and internal fixation were reviewed. Patients were followed up for an
      average of 3.5 years (range, 1-13 years). Fracture reductions were graded as
      anatomic (0-1 mm displacement) in 92 patients and imperfect (2-3 mm displacement)
      in two patients, as determined by plain radiography. However, postoperative
      computed tomography scans obtained in 59 patients revealed incongruency of more
      than 2 mm in six patients and fracture gaps of 2 mm or more in 44 patients.
      Complications included deep wound infection (one patient), deep vein thrombosis,
      (seven patients), and revision surgery to redirect an errant screw (one patient).
      Clinical outcome was graded as excellent in 34 patients (36%), good in 49 (52%),
      fair in two (2%), and poor in nine (10%). Radiographic results were excellent in
      79 hips (84%), good in four (4%), fair in two (2%), and poor in nine (10%). There
      was a strong association between clinical outcome and radiographic grade.
      Variables identified as risk factors for an unsatisfactory result included age
      greater than 55 years, a delay greater than 24 hours from the time of injury for
      reduction of a hip dislocation, a residual fracture gap greater than 1 cm, and
      severe intraarticular comminution. The apparent disparity between the accuracy of
      surgical fracture reduction, as determined by plain radiographs obtained
      postoperatively, and clinical outcome is explained only partially by the
      limitations of plain radiography. Other variables are involved, many of which are
      under the surgeon's control but some are not. As is the case with other
      acetabular fracture types, the best results are predicated on anatomic fracture
      reduction.

PMID- 10943186
TI  - Osteonecrosis of the femoral head after traumatic hip dislocation in the adult.
AB  - Osteonecrosis of the femoral head is most commonly classified according to the
      system of Ficat and Arlet, and the choice of treatment is based directly on the
      corresponding stage. Therefore it is important to accurately determine the stage
      of the disease because it has important bearings on the patient's clinical
      course. Patients with Stage I lesions (preradiologic stage of the disease)
      usually can be treated with pulsed electromagnetic fields with or without a core
      decompression, bone grafting and decompression, and rotational intertrochanteric
      osteotomy. These procedures are equally applicable for patients with Stage II
      lesions but frequently additional measures such as vascularized fibular grafting
      and intertrochanteric osteotomy may be necessary. Patients with Stages III and IV
      lesions also may be treated in a similar way, especially if one wishes to avoid
      total hip arthroplasty, especially in younger patients. The trapdoor procedure
      with autogenous cancellous bone and cortical bone grafting can be successful in
      Stage III osteonecrosis of the hip in patients with small- to medium-sized
      lesions. When core decompression is used to treat patients with Stage III
      lesions, an 89% satisfactory outcome can be expected providing that the lesion is
      small and central, and does not have head depression. Many times the number and
      variety of procedures tend to reflect the relatively poor results and the desire
      to avoid total hip arthroplasty. Arthrodesis continues to be an excellent and
      predictable treatment option and may be indicated when unilateral trauma is the
      etiology.

PMID- 10943187
TI  - Knee injuries in traumatic hip dislocation.
AB  - Of 187 patients treated at the author's institutions for fracture and/or
      dislocation of the hip during a 10-year period (1985-1994), 46 patients (25%)
      with a knee injury on the same side as the hip injury were evaluated 6 months to
      11 years after the initial accident (mean, 3.65 years). Thirty-nine patients
      (85%) had symptoms or clinical signs in the knee. Ligamentous injuries overlooked
      in the initial examination were found in seven patients. Knee injuries often
      accompany hip fracture and/or dislocation, and can be produced by direct or
      indirect trauma. A delayed diagnosis of such injuries may lead to their treatment
      in the sequela phase, which complicates the final outcome. Therefore, an
      exhaustive physical examination is recommended for patients with traumatic hip
      dislocation to detect potential injuries to the ipsilateral knee. Early diagnosis
      and treatment of such injuries greatly improve final outcome.

PMID- 10943188
TI  - Nerve injury in traumatic dislocation of the hip.
AB  - Neurologic injury often accompanies traumatic dislocation and fracture
      dislocation of the hip. A review of the literature reveals an incidence of
      approximately 10% in adults and 5% in children. The sciatic nerve, usually the
      peroneal branch, is most often injured, and this complication can be seen after
      all types of posterior fracture-dislocations and simple posterior dislocations.
      The sciatic nerve can be acutely lacerated, stretched, or compressed, or later
      encased in heterotopic ossification. Neurologic examination at the time of injury
      often is difficult but is extremely important. Once a nerve injury is discovered,
      prompt closed reduction must be attempted to relieve distortion of the nerve from
      a dislocated femoral head or displaced acetabular fracture. Considerable
      controversy surrounds the recommendations for additional treatment of nerve
      injury once the hip has been reduced. At least partial recovery of nerve function
      occurs in 60% to 70% of patients, with no clear correlation with injury or
      treatment type. Rehabilitation of patients with sciatic nerve injury must begin
      as early as possible and should focus on the prevention of an equinus foot
      deformity. Magnetic resonance neurography may become useful in the future for
      initial evaluation of patients with this injury.

PMID- 10943189
TI  - Coxarthrosis after traumatic hip dislocation in the adult.
AB  - Sixteen percent of patients with uncomplicated hip dislocations have
      posttraumatic arthritis develop. Incidences as high as 88% are reported for
      patients with dislocations associated with severe acetabular fractures. The
      surgical treatment of patients with posttraumatic arthritis includes arthroscopy,
      arthrodesis, osteotomy, and arthroplasty. Although arthroplasty offers the best
      solution for the painful arthritic hip in the older or inactive patient, the
      treatment of an active patient in the prime of life with severe osteoarthritis of
      the hip is problematic. In the younger, active patient, it may be prudent to
      consider alternative treatment in an attempt to avoid, or delay, total hip
      arthroplasty. Although improving the longevity of primary arthroplasty is
      desirable, measures to prevent or delay the onset of the osteoarthritis seem more
      appropriate. Arthroscopic lavage, debridement and chondral abrasion, and
      osteochondral fragment removal after dislocation may have a role in the treatment
      of young patients with the early stages of coxarthrosis. Any patient with
      isolated posttraumatic arthritis of the hip who has a life expectancy greater
      than 30 years may be a candidate for hip arthrodesis. The ideal candidates for
      hip arthrodesis are only laborers younger than 35 years of age. Osteotomy of the
      hip for posttraumatic arthritis remains an appealing alternative for many
      patients because of the long-term failures of total hip arthroplasty. The
      clinical results of osteotomy are variable and do not match the results of a
      total hip arthroplasty. However, primary arthroplasty may fail, and revision
      arthroplasty is routinely more difficult and shorter lived than the primary
      operation.

PMID- 10943190
TI  - Hip dislocation in patients with multiple injuries. A followup investigation.
AB  - The combination of traumatic hip dislocation and multiple trauma have not been
      well documented in the medical literature to date. The role of surgery therefore
      has not been well defined in these patients. During a 12-year period, 29
      consecutive patients with 31 traumatic hip dislocations with concomitant Injury
      Severity Scores exceeding 18 points were treated at the authors' institution. An
      initial satisfactory closed reduction was achieved in 23 patients, two patients
      had failed reductions, and four patients had noncongruous reductions. Open
      surgical procedures were done on these patients and on 10 additional patients who
      had associated acetabular or femoral head fractures. Overall, seven patients from
      the group died including two patients who had surgical procedures. From 17 living
      patients who did not require surgery for failed or noncongruous reductions, 13
      patients were available for followup at a mean of 8 years after their injury. The
      clinical results at this followup were excellent in three hips, good in seven
      hips, and fair in four hips. The radiologic results, however, showed that five
      patients had early (Grades I and II according to Matta) hip degeneration and
      seven patients had Grade II (according to Ficat) avascular necrosis of the
      femoral head. These changes were not clinically significant at this followup and
      it is proposed that these results justify a policy of active treatment of
      traumatic hip dislocation in patients with multitrauma.

PMID- 10943191
TI  - Traumatic dislocation of the hip in children.
AB  - In the current study, the incidence, presentation, and treatment of traumatic
      dislocation of the hip in children will be discussed. The complications and the
      possible pathologic changes behind the development of avascular necrosis are
      described. Most children have a good outcome after this injury, perhaps because a
      concomitant fracture is unusual. The results in children are significantly better
      than results in adults.

PMID- 10943192
TI  - Zoster paresis of the shoulder. Case report and review of the literature.
AB  - More than 95% of people in the United States are infected with the varicella
      zoster virus at some time in life, and this infection usually is manifested as
      chicken pox during childhood. The virus then establishes a latent infection of
      sensory ganglia, from which it may reactivate many years later to cause herpes
      zoster (shingles), a cutaneous painful rash along a dermatomal distribution. Less
      commonly, the varicella zoster virus may result in myotomal motor weakness or
      paralysis in addition to a painful dermatomal rash. A case of unilateral left C5
      C6 segmental paresis attributable to herpes zoster in an otherwise healthy
      individual and a current review of the literature are presented. A case of zoster
      paresis of the shoulder muscles is presented to remind the orthopaedic community
      that this diagnosis may be confused with other diagnoses, including rotator cuff
      tear, and should be considered in the differential diagnosis of shoulder pain and
      shoulder girdle muscle weakness.

PMID- 10943193
TI  - Growth factor expression in the osteophytes of the human femoral head in
      osteoarthritis.
AB  - Osteoarthritis is characterized by marked osteophyte formation consisting of new
      cartilage and bone. Because several growth factors are known to be involved in
      chondrogenesis and osteogenesis, the expression of transforming growth factor
      beta 1 and basic fibroblast growth factor in the osteophytes of the human femoral
      heads in osteoarthritis were examined. Transforming growth factor-beta 1
      messenger ribonucleic acid was detected in the osteophytes by reverse
      transcription-polymerase chain reaction. All of the nine examined osteophytes
      expressed transforming growth factor-beta 1 messenger ribonucleic acid, whereas
      one of four osteoarthritic femoral heads and none of four osteonecrotic femoral
      heads expressed transforming growth factor-beta 1 messenger ribonucleic acid. The
      extent of transforming growth factor-beta 1 messenger ribonucleic acid expression
      varied among the osteophytes. Transforming growth factor-beta 1 or basic
      fibroblast growth factor was analyzed in osteophytes immunohistochemically.
      Transforming growth factor-beta 1 was localized in the superficial cells in the
      osteophyte cartilage, but it was scarcely detected in the superficial cells in
      the degenerative articular cartilage. Basic fibroblast growth factor was detected
      in the cells in the whole layer of osteophyte cartilage and in the articular
      cartilage. There was a difference in the localization, which suggests the
      different roles of transforming growth factor-beta 1 and basic fibroblast growth
      factor in bone and cartilage metabolism in osteophyte formation.

PMID- 10943195
TI  - Delayed proximal repair and distal realignment after patellar dislocation.
AB  - Twenty athletes with distal malalignment who sustained unilateral traumatic
      patellar dislocation remained impaired by chronic instability. Surgery was
      performed at a mean age of 18 years. Posttraumatic attenuation of the medial
      patellofemoral ligament was repaired near the margin of the patella in 10 knees
      and avulsion or attenuation posterior to the vastus medialis obliquus in 10
      knees. Advancement of the medial patellomeniscal ligament at the margin of the
      patella and normalization of the Q angle to 10 degrees by tibial tubercle
      osteotomy were performed in each knee. Distal lateral retinacular release without
      release of the normal vastus lateralis tendon was performed. Results were judged
      according to Turba et al, and activity levels were evaluated per guidelines of
      the International Knee Documentation Committee. Eighteen (90%) patients achieved
      good or excellent results and were unimpaired at a minimum of 24 months. Two
      patients achieved fair subjective results with some impairment in vigorous
      activity. There was no recurrent instability. Radiographically, the mean
      preoperative patellofemoral congruence angle improved from 20 degrees to 0
      degree. Athletes who sustain an initial traumatic patellar dislocation after
      physeal closure and in whom conservative management fails can be treated
      successfully by repair of the medial patellofemoral ligament at the site of
      disruption and advancement of the medial patellomeniscal ligament combined with
      correction of an elevated Q angle.

PMID- 10943194
TI  - Elevated levels of lipoprotein(a) in familial bone marrow edema syndrome of the
      hip.
AB  - There is controversy whether bone marrow edema syndrome represents a distinct
      transient disease or reflects an early reversible phase of spontaneous
      osteonecrosis of the hip. Hypofibrinolysis on the basis of elevated plasma levels
      of plasminogen activator inhibitor or lipoprotein(a) or both has been reported to
      favor the development of bone marrow edema syndrome and nontraumatic avascular
      necrosis. The current authors report on the familial occurrence of transient bone
      marrow edema syndrome of the hip in three female family members. Plasma
      concentrations of lipoprotein(a) were elevated in all three patients, whereas
      serum levels of plasminogen activator inhibitor were within normal ranges. This
      first familial description of transient bone marrow edema syndrome of the hip
      strongly suggests that a genetically determined elevation of lipoprotein(a) may
      be an important predisposing factor in these patients.

PMID- 10943196
TI  - Osteochondral defects in the knee. A treatment using lateral patella autografts.
AB  - Sixteen patients (13 males and three females; average age, 27 years) with large
      symptomatic osteochondral defects of the femoral condyle were treated with an
      osteochondral autograft taken from the ipsilateral lateral patellar facet. Two
      patients had bilateral procedures for a total of 18 knees. These patients were
      followed up prospectively with an average followup of 7.6 years (range, 2-14.6
      years). Cincinnati knee scores showed significant changes, from an average
      preoperative score of 37 to an average final followup score of 85. In all of the
      patients, knee function was improved, and they were able to return to their
      normal lifestyle with minimal or no restriction. Eighty-one percent of patients
      have returned to a high level of functioning.

PMID- 10943197
TI  - Gastrocnemius myotendinous flap for patellar or quadriceps tendon repair, or
      both.
AB  - The authors' experience with simultaneous reconstruction of the quadriceps
      femoris or patellar tendon or both and soft tissue defect using a
      musculotendinous unit of the gastrocnemius muscle is presented. Five patients
      with a partial or complete defect of the quadriceps or patellar tendon or both
      and additional large soft tissue defects underwent reconstruction applying this
      technique as a one-stage surgical procedure in different variations. In cases
      with a partial defect of the tendon or loss of tendon thickness, the thick
      aponeurosis from the deeper aspect of the gastrocnemius was dissected and
      transferred as a pedicled tendon flap to reconstruct the tendon defect. In cases
      with a complete defect of the tendon, the superficial layer of the Achilles
      tendon together with the deep aponeurotic layer of the gastrocnemius muscle
      served to reconstruct the tendon. In both procedures the gastrocnemius muscle
      belly provided soft tissue coverage and was covered with a split thickness skin
      graft. One patient had a marginal deep necrosis develop that had to be covered
      with the other gastrocnemius muscle in a second operation. One patient with
      chronic polyarthritis and infection of his knee prosthesis declined additional
      reconstruction surgery and had the leg amputated. The average followup was 3.5
      years. All patients achieved good results in active extension of the knee with an
      extension deficit of only 5 degrees to 15 degrees. The range of flexion was at
      least 90 degrees. The surgical technique described in this report provides
      functional tendon reconstruction and adequate soft tissue repair simultaneously.

PMID- 10943198
TI  - Factors affecting long-term results after arthroscopic partial meniscectomy.
AB  - The purpose of this study was to determine functional and radiographic changes on
      long-term followup of knees with isolated meniscal tears. Sixty-seven patients
      were evaluated retrospectively with an average of 12.2 years' followup using the
      scale of Tapper and Hoover. The criteria for the radiographic results were the
      Fairbank's changes as the standard comparing the preoperative and the
      postoperative conditions of the affected knee with the contralateral knee.
      Seventy-nine percent of the patients had a satisfactory outcome in terms of
      function. The amount of meniscus removed and the Outerbridge classification of
      the articular cartilage at the time of the meniscectomy were determining factors
      for long-term functional results. Osteoarthritic deterioration was seen in 48% of
      patients after the surgery, but radiographic deterioration after arthroscopic
      partial meniscectomy was mild on long-term followup. Medial meniscectomy and the
      amount of meniscus removed were risk factors for postoperative radiographic
      change. Age, gender, and the degree of cartilage degeneration at the time of
      operation, in contrast, showed no significant association. Arthroscopic partial
      meniscectomy for isolated meniscal injury yields favorable functional results but
      leads to significantly increased osteoarthritic change in the long-term.

PMID- 10943199
TI  - Curve progression and spinal growth in brace treated idiopathic scoliosis.
AB  - The risk of progression of idiopathic scoliosis is correlated primarily to
      factors that predict potential remaining skeletal growth. The aim of the current
      study was to evaluate spinal growth, measured as the length of the scoliotic
      spine on serial longitudinal radiographs, and its relationship to progression of
      the scoliotic curve. The retrospective study was based on measurements made on
      standing anteroposterior radiographs of 60 patients with adolescent idiopathic
      scoliosis. In all patients, a Boston brace was prescribed during the followup
      period. Despite brace treatment, a significantly greater average progression rate
      of the scoliotic curve was seen in periods of rapid to moderate growth (> or = 10
      mm per year) compared with periods of small or no growth (< 10 mm per year). The
      difference in progression rates concerned the increase of the Cobb angle and the
      increase of lateral deviation and axial rotation. These findings indicate the
      length of the spine measured on subsequent radiographs is an excellent parameter
      to determine spinal growth and thus an excellent predictor of scoliosis
      progression. With the presented growth charts, which were derived from the
      measured individual growth velocity values of the patients in the study, it is
      possible to predict future spinal growth at different chronologic ages.

PMID- 10943200
TI  - Thoracolumbar kyphoscoliosis in Larsen's syndrome. A case report.
AB  - Severe thoracolumbar kyphosis in Larsen's syndrome is rare. A successful 10-year
      treatment course, including T2-L4 subfascial rod placement when the patient was 6
      years 3 months of age, nine periodic lengthenings, and definitive surgery at age
      14 years 4 months is presented. From preoperative to 2-year postoperative
      definitive surgery, the patient's T1 to S1 spine length increased from 19 to 36
      cm. The patient's 83 degrees thoracolumbar kyphosis was transformed to 45 degrees
      kyphosis and 28 degrees lumbar lordosis, and scolioses of 95 degrees and 65
      degrees were reduced to 64 degrees and 50 degrees.

PMID- 10943201
TI  - Massive bone allograft reconstruction in high-grade osteosarcoma.
AB  - From 1986 to 1994, 112 bone allograft reconstructions were performed in patients
      with high-grade osteosarcoma in whom neoadjuvant chemotherapy was administered.
      The allograft reconstruction was used in arthrodesis in 44 cases (41 knees, three
      ankles), as an intercalary graft in 39 (28 femurs, 11 tibias), as an
      osteoarticular graft in 22 (three proximal and/or distal humeri, six distal
      femurs, 13 proximal tibias), and as an allograft and prosthesis composite in
      seven (two proximal humeri, one proximal femurs, four proximal tibias). In 20
      patients an autologous vascularized fibula was used to augment the allograft.
      Functional results were excellent or good in 74% of the patients after the
      primary surgery, and in 83% of the patients after secondary surgery.
      Complications include delayed union (49%) and fracture (27%), although there were
      no cases of deep infection. The incidence of delayed union, but not infection or
      fracture, was increased by the use of chemotherapy.

PMID- 10943202
TI  - Analysis of 12q13-15 genes in parosteal osteosarcoma.
AB  - The region q13-15 of chromosome 12 frequently is altered in human sarcomas, and
      several genes, such as SAS, CDK4, and MDM2, have been found to be amplified in
      bone and soft tissue sarcomas. These genes and their products were studied by
      quantitative polymerase chain reaction and immunohistochemical analysis in 25
      parosteal osteosarcoma samples (22 Grades I or II, three dedifferentiated) to
      evaluate if the possible alterations detected of the genes on chromosome 12 could
      have a role in the development of this rare bone tumor. Immunohistochemical
      analysis was performed on formalin fixed, paraffin embedded tumor sections to
      evaluate CDK4 and MDM2 protein expression. To measure the degree of SAS and CDK4
      gene amplification, quantitative polymerase chain reaction was done on
      deoxyribonucleic acid derived from the same samples. The results showed that CDK4
      protein was expressed in 92% of the cases. Strong and uniform CDK4 and MDM2
      immunoreactivity was found respectively in three of three and two of three
      dedifferentiated parosteal osteosarcomas. SAS and CDK4 genes were found to be
      amplified fourfold in two Grade II tumors and in one dedifferentiated tumor.
      These findings, which should be investigated further, might suggest a possible
      role of the chromosome 12 genes in the pathogenesis of parosteal osteosarcoma.

PMID- 10943203
TI  - Primary rhabdomyosarcoma of long bone. A case report.
AB  - A case of rhabdomyosarcoma of the femur in a 45-year-old man is reported. The
      patient had a good response to intraarterial chemotherapy and was functionally
      well 4 years after limb salvage surgery.

PMID- 10943204
TI  - Calcaneus fractures with subluxation of the posterior facet. A surgical
      indication.
AB  - The charts and radiographs of 118 patients with 126 intraarticular fractures of
      the calcaneus were reviewed retrospectively. Eleven of 126 (8.7%) calcaneal
      fractures had injuries consisting of intraarticular calcaneal fracture, lateral
      subluxation or dislocation of the posterior facet, fracture extension into the
      calcaneocuboid joint, peroneal tendon subluxation, subluxation of the talus in
      the ankle mortise, and complete disruption of the anterior talofibular and
      calcaneal fibular ligaments or fracture of the lateral malleolus. There were six
      women and five men. The average age was 40 years (range, 17-65 years). The
      mechanism of injury was a motor vehicle accident in eight and a fall from a
      height in three. According to the classification of Sanders et al eight fractures
      were Type II, one was Type III, and two were Type IV. Followup at an average of
      26 months (range, 14-38 months) showed that eight of 11 patients (72.7%) had
      either good or excellent results. When lateral subluxation of the posterior facet
      of the calcaneus is identified with a preoperative computed tomography scan,
      operative management is indicated, and the surgeon should search for associated
      injuries that should be addressed at the time of surgery.

PMID- 10943205
TI  - Should calcaneal fractures be treated surgically? A meta-analysis.
AB  - A MEDLINE search from 1980 through 1996 revealed 1845 articles dealing with
      calcaneal fractures. Six of these articles that compared operative versus
      nonoperative treatment for displaced calcaneal fractures met the minimum criteria
      for inclusion in a meta-analysis. A statistical summary of information across the
      six articles revealed a trend for surgically treated patients to be more likely
      to return to the same type of work as compared with nonoperatively treated
      individuals. There also was a trend for nonoperatively treated patients to have a
      higher risk of experiencing severe foot pain than did operatively treated
      patients. Unfortunately, none of the other outcomes could be summarized formally
      across studies using statistical techniques because of variability in reporting
      across studies. Although the tendency was always for operatively treated patients
      to have better outcomes (reaching statistical significance in some of the
      articles), the strength of evidence to recommend operative treatment for
      displaced intraarticular calcaneal fractures remains weak. A large prospective
      randomized controlled trial should be able to answer this question.

PMID- 10943206
TI  - In vitro biomechanical evaluation of the double loop suture for flexor tendon
      repair.
AB  - Fifty-one fresh frozen human anatomic specimen flexor superficialis and profundus
      tendons that had been transected completely were repaired using the double loop,
      the single loop, and the modified Kessler techniques, and the resistances to
      mechanical distraction at 1, 2, and 3 mm and the ultimate load to failure were
      compared. The mechanical distraction at 1, 2, and 3 mm created nearly identical
      gaps at the tendon repair sites. There was no significant difference among the
      three repair techniques to resisting distraction at 1 and 2 mm. However, the
      double loop technique presented a mean resistance force of 22.0 N to distraction
      at 3 mm and 45.8 N in load to failure, which was significantly greater than the
      single loop (18.8 N at 3 mm distraction and 31.5 N failure load) and the modified
      Kessler (19.0 N at 3 mm distraction and 26.0 N failure load). This suggests the
      double loop technique may be superior to the single loop and the modified Kessler
      techniques in resisting gap in the range of forces generated in the early
      rehabilitation protocol.

PMID- 10943207
TI  - A biomechanical comparison of Schuhli nuts or cement augmented screws for plating
      of humeral fractures.
AB  - Schuhli locking nuts can be used in poor quality cortical bone to enhance
      fixation stability as an alternative to cement augmented screws. This study
      compared the fixation strength and stability of plate constructs using Schuhli
      locking nuts with standard screws and cement augmented screws for fixation of
      simulated humeral shaft fractures in a test model with osteoporosis. The
      constructs were tested in axial compression, 4-point bending, and torsion to
      determine fixation stability. The humeri were cycled in torsion (4.5 Nm) for 1000
      cycles to simulate upper extremity use during the early postoperative period and
      retested for stability. The Schuhli locking nuts and cement augmented screws had
      significantly greater fixation stability than the standard screws before (range,
      6-14 times greater) and after cycling in torsional loading (range, 3-3.6 times
      greater). Although cement augmented screws and Schuhli augmentation showed
      increased fixation stability compared with the standard screws in axial and 4
      point bending before cycling (range, 1.3-1.4 times greater), this was not
      significant. Compared with Schuhli fixation, cement augmented screws showed no
      significant difference in fixation stability in all loading modes before and
      after cycling. Schuhli locking nuts offer the stability of cement augmentation
      while avoiding its potential adverse effects on fracture healing with
      extravasation and thermal necrosis.

PMID- 10943208
TI  - Serum creatine kinase isoenzyme BB in mammalian osteopetrosis.
AB  - In mammalian osteopetrosis the different mutations exemplify reduced bone
      resorption leading to net accumulation of bone. Recently, high blood levels of
      creatine kinase-BB have been reported in some human forms, suggesting it as a
      marker of osteopetrosis. In the current study serum creatine kinase-BB was
      evaluated in relation to known osteoclastic pathophysiology in two human types of
      autosomal dominant osteopetrosis at baseline and after stimulation with
      triiodothyronine and in four different rodent mutations. Creatine kinase-BB was
      increased markedly in Type 2 autosomal dominant osteopetrosis and in the incisors
      absent rat, both characterized by large numbers of giant osteoclasts, and did not
      change significantly after stimulation. Although creatine kinase-BB was unchanged
      in Type 1 autosomal dominant osteopetrosis at baseline and after stimulation, the
      rodent counterparts characterized by small osteoclasts, microphthalmic and
      osteopetrotic mice and toothless rats, had significantly decreased levels.
      Similar differences were observed in both types of autosomal dominant
      osteopetrosis compared with controls concerning tartrate resistant acid
      phosphatase. Creatine kinase-BB in mammalian osteopetrosis is related to
      osteoclastic number and size, where it probably reflects the differentiation and
      maturation of inactive bone resorbing cells. The isoenzyme does not seem to be a
      valuable screening marker for osteopetrosis.

PMID- 10943209
TI  - Cartilage repair with autogenic perichondrium cell and polylactic acid grafts.
AB  - The repair of articular cartilage injuries remains a challenge, with many of the
      current therapeutic strategies based on the grafting or recruitment of
      chondrogenic tissues or cells. This 1-year study compared the repair of a 3.7-mm
      diameter by 3-mm deep osteochondral defect in the medial femoral condyle of 24
      New Zealand White rabbits; the defect was obtained using an autogenic
      perichondrium cell polylactic acid composite graft with a contralateral control
      in which the osteochondral defect remained empty. To elucidate the effect of host
      immune responses on the repair process after perichondrium cell transplantation,
      the results of the autogenic perichondrium cell polylactic acid graft group were
      compared with those obtained in the authors' previous 1-year study of allogenic
      perichondrium cell polylactic acid composite grafts implanted in a similar model.
      One year after surgery, the repair site underwent gross inspection and
      histologic, histomorphometric, biochemical, and biomechanical analyses. The
      autogenic perichondrium cell polylactic acid graft group (92%) and the control
      group in which the osteochondral defect remained empty (88%) resulted in a high
      percentage of grossly acceptable repairs. The autogenic grafts appeared to
      augment the intrinsic healing capacity of the animals (as compared with the
      animals in the No Implant Group). The autogenic perichondrium cell polylactic and
      grafts improved the histologic appearance and percentage of Type II collagen of
      the cartilaginous repair tissue. Compared with allogenic grafts, the autogenic
      grafts had better reconstitution of the subchondral bone. However, the results of
      this experimental model suggest a suboptimal concentration of glycosaminoglycans
      in the neocartilage matrix, a depressed surface of the repair tissue, a
      histologic appearance that was not equivalent to that of normal articular
      cartilage, and reduced biomechanical properties for the repair tissue. The future
      application of growth factors to this model may yield a treatment that can be
      applied in the clinical arena.

PMID- 10943210
TI  - Chondronecrosis of the hip. The protective role of the ossific nucleus in an
      animal model.
AB  - The presence of the ossific nucleus and its role in reducing the risk of ischemic
      necrosis in developmental dysplasia of the hip remains a matter of controversy.
      Ischemic necrosis of the pre-osseous capital femoral epiphysis, defined as
      chondronecrosis, was evaluated in a rabbit model. Histologic evidence of
      chondronecrosis after casting in maximum abduction was greater in 1-day-old New
      Zealand White rabbits before the radiographic appearance of the ossific nucleus,
      compared with 16-day-old New Zealand White rabbits with an ossific nucleus
      already present. This preliminary study supports the hypothesis that the ossific
      nucleus may decrease the risk of intracapsular compressive ischemic injury to the
      developing capital femoral epiphysis in a rabbit model.

PMID- 10943211
TI  - Distal femoral lytic lesion in a 14-year-old boy.

PMID- 10943212
TI  - 15 cases of dislocation of the first metatarsophalangeal joint have been
      reported.

PMID- 10943213
TI  - [Guidelines, recommendations and positions].

PMID- 10943214
TI  - [Upcoding--a risk for the use of diagnosis-related groups].
AB  - BACKGROUND: Upcoding id defined by a systematic and deliberate shift in the case
      mix of a hospital in order to improve reimbursement. Upcoding is frequently
      mentioned as a reason for ineffective reimbursement under a DRG payment system.
      METHOD: A systematic literature search identified relevant studies concerning the
      extent of the Upcoding. Results are used for estimating the magnitude of Upcoding
      in Germany. RESULTS: Studies showed different estimates for Upcoding. Transferred
      to Germany roughly up to 1% of the payments for inpatient care are estimated to
      Upcoding. After 4 to 5 years the level of Upcoding decreases. To what extent
      Upcoding could be taken into account when setting the DRG reimbursement fees,
      remains open. Regarding the creation of epidemiological time series Upcoding
      causes a abrupt change in statistics. However this disadvantage is offset by the
      more complete coding under a DRG payment system. CONSEQUENCES: When setting the
      DRG reimbursement fees the elimination of the contribution of Upcoding share to
      the total shift in case mix can only be done retrospectively. Thus a rule for
      compensation of subsequent years is likely. Likewise the possibly different
      distribution of Upcoding among hospitals and their departments requires further
      investigation.

PMID- 10943215
TI  - [The Referral Field Hospital of the Emergency Response Unit (ERU) of the German
      Red Cross].
AB  - INTRODUCTION: Emergency Response units (ERUs) have been developed as a part of
      the International Federation of Red Cross and Red Crescent Societies strategy to
      provide fast and effective medical and technical help to victims of disasters of
      any kind. ERUs provide timely, professional and organised response in a
      standardised and streamlined way by a balanced composition of professional staff
      and predesigned equipment. METHODS: The German Red Cross ERUs "Referral Hospital"
      and "Specialised Water" took part in the world wide humanitarian help for
      refugees during the Kosovo war and actually for earthquake victims in Turkey.
      During the Kosovo-operation the ERU "Referral Hospital" and "Specialised Water"
      were situated in Macedonia close to the kosovarian boarder at refugee camp
      Stenkovec I. The Field-Hospital was responsible for all kind of medical
      emergencies, for a total number of more than 50,000 refugees. RESULTS: During the
      mission 6225 patients were treated in our Out Patient Department; 541 were
      hospitalised. Among those 102 medium and major surgical procedures and 105
      deliveries were performed. Surprisingly there was no increased rate of infections
      or perinatal deaths. CONCLUSIONS: During the Kosovo war and actually in Turkey
      the ERU concept prove itself to be a powerful strategy to provide fast needed
      medical help to victims of different kind of disasters. Humanitarian work in
      situations of war, internal disorder and various states of emergency in foreign
      countries and cultures demand flexibility and the ability to improvise while
      working under such conditions. The confrontation with non-combatants injured by
      buried landmines is underlining the growing world-wide demand for a total ban on
      these vile weapons.

PMID- 10943216
TI  - [Late spreading of tuberculosis in tubercular spondylitis].
AB  - HISTORY AND ADMISSION DIAGNOSIS: A 65-year-old man, known to have had a gastric
      ulcer and chronic rheumatoid arthritis as well as alcohol and nicotine abuse, was
      admitted because of suspected endocarditis. Physical examination revealed marked
      pain on pressure over the throacic spine. Vesicular breath sounds were reduced
      over the entire thorax and there was a systolic murmur over Erb's point (above
      the right clavicle). There was a purulent bursitis over the olecranon.
      INVESTIGATIONS: Abnormal laboratory tests were: elevated C-reactive protein,
      elevated leucocyte count (up to 33 thousand during the hospital stay). Smears
      from the bursitis and blood cultures revealed Staph. aureus. Computed tomography
      demonstrated a fracture of the 7th thoracic vertebra with a paravertebral
      abscess. Echocardiography showed anatherosclerotic aortic valve with floating
      particles. DIAGNOSIS, TREATMENT AND COURSE: Treatment of the suspected
      staphylococcal bacteraemia with purulent bursitis, spondylitis and aortic valvar
      endocarditis was begun with broad-spectrum antibiotics, but the patient soon
      developed a severe acute respiratory distress syndrome and he died of multi-organ
      failure. Autopsy revealed as cause of death left heart failure with aortic valvar
      endocarditis and gelatinour pneumonia caused by late tubercular dissemination
      from the tubercular spondylitis. CONCLUSION: Tuberculosis can be a life
      threatening infection. Uncharacteristic history and extrapulmonary manifestations
      can make it very difficult to arrive at the correct diagnosis.

PMID- 10943217
TI  - [Tubercular psoas abscess].
AB  - HISTORY AND ADMISSION FINDINGS: A 43-year-old patient suffered from fatigue,
      nocturnal sweating, rigor and a weight loss of 5 kg over the last 4 weeks. A year
      before he had been anaemic and he was treated with omeprazole and iron. On
      admission physical examination was unremarkable, except for the known swelling in
      the right flank. His general condition was good. INVESTIGATIONS: Computed
      tomography showed an extensive abscess of the right psoas muscle with deplacement
      of the right ureter, causing hydronephrosis, and infiltration of the abdominal
      wall. Cytological and bacteriological tests of the abscess aspirate indicated
      tuberculosis. TREATMENT AND COURSE: The abscess markedly shrank within 2 months
      of starting antituberculosis treatment, which was continued for another 4 months.
      A catheter, which had been inserted into the right ureter to relieve
      hydronephrosis, was remowed without further complications. CONCLUSION: Because of
      an increase in the number of immigrants from countries with a high incidence of
      tuberculosis or HIV infection, extrapulmonary tuberculosis should be included in
      the differential diagnosis, such as in this case of a psoas muscle abscess.
      Despite the size of the abscess surgical intervention is rarely required because
      it will heal under appropriate antituberculosis treatment.

PMID- 10943218
TI  - [New developments in phototherapy].

PMID- 10943219
TI  - [Hantavirus infections].

PMID- 10943220
TI  - [Primary and secondary prevention of coronary heart disease. A position paper of
      the International Task Force for the Prevention of Coronary Heart Disease].

PMID- 10943221
TI  - [Surgical strategies for the treatment of chronic mitral valve insufficiency].

PMID- 10943222
TI  - Preventing, stopping, or reversing coronary artery disease--triglyceride-rich
      lipoproteins and associated lipoprotein and metabolic abnormalities: the need for
      recognition and treatment.
AB  - A substantial number of treated patients with or at high risk for coronary artery
      disease continue to have fatal and nonfatal coronary artery events in spite of
      significant reduction of elevated levels of low-density lipoprotein cholesterol.
      Other lipoprotein abnormalities besides an elevated level of low-density
      lipoprotein cholesterol contribute to risk of coronary artery disease and
      coronary artery events, and the predominant abnormalities that appear to explain
      much of this continued risk are an elevated serum triglyceride level and a low
      level of high-density lipoprotein cholesterol. Most patients with coronary artery
      disease have a mixed dyslipidemia with hypertriglyceridemia, which is associated
      and metabolically intertwined with other atherogenic risk factors, including the
      presence of triglyceride-rich lipoprotein remnants, low levels of high-density
      lipoprotein cholesterol, small, dense, low-density lipoprotein particles,
      postprandial hyperlipidemia, and a prothrombotic state. Aggressive treatment of
      these patients needs to focus on these other lipoprotein abnormalities as much as
      on low-density lipoprotein cholesterol. Combination drug therapy will usually be
      required. Reliable assessment of risk of coronary artery disease from lipoprotein
      measurements and response to therapy requires inclusion of all atherogenic
      lipoproteins in laboratory measurements and treatment protocols. At present this
      may be best accomplished by use of non-high-density lipoprotein cholesterol
      (total cholesterol minus high-density lipoprotein cholesterol) calculated from
      standard laboratory lipoprotein values. Ultimately, a more comprehensive
      assessment of coronary artery disease risk and appropriate therapy may include
      measurement of lipoprotein subclass distribution including determination of low
      density lipoprotein particle concentration and sizes of the various lipoprotein
      particles.

PMID- 10943223
TI  - Time travel.

PMID- 10943224
TI  - Quality improvement movement--jump start from the Leapfrog Group.

PMID- 10943225
TI  - From promises to performance: a look at four innovative technology packages that
      might revolutionize health care.

PMID- 10943226
TI  - Blood feud.

PMID- 10943227
TI  - E-health goes to the doctor. Affordable technology opens portals for physician
      practices.

PMID- 10943228
TI  - In the borderland between health and disease following the Gulf War.

PMID- 10943229
TI  - Triptans to the rescue: effective therapy for migraine headaches in the
      workplace.

PMID- 10943230
TI  - Effectiveness of sumatriptan in reducing productivity loss due to migraine:
      results of a randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To determine the effect of sumatriptan on migraine-related workplace
      productivity loss. PATIENTS AND METHODS: In this randomized, double-blind,
      placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of
      sumatriptan or matching placebo to treat a moderate or severe migraine within the
      first 4 hours of a minimum of an 8-hour work shift. Outcome measures included
      productivity loss and number of patients returning to normal work performance 2
      hours after injection and across the work shift, time to return to normal work
      performance, and time to headache relief. RESULTS: A total of 206 patients
      underwent screening, 140 (safety population) of whom returned for clinic
      treatment. Of these 140 patients, 119 received migraine treatment in the
      workplace (intent-to-treat population), 116 of whom comprised the study
      population. Of these 116 patients, 76 self-administered sumatriptan, and 40 self
      administered placebo. Sumatriptan treatment tended to reduce median productivity
      loss 2 hours after injection compared with placebo (25.2 vs 29.9 minutes,
      respectively; P = .14). Significant reductions in productivity loss were obtained
      across the work shift after sumatriptan treatment compared with placebo (36.8 vs
      72.6 minutes, respectively; P = .001). Significantly more sumatriptan-treated
      patients vs placebo-treated patients experienced shorter return to normal work
      performance at 2 hours (53/76 [70%] vs 12/40 [30%], respectively) and across the
      work shift (64/76 [84%] vs 23/40 [58%], respectively; P < .001). Significantly
      more sumatriptan-treated patients experienced headache relief 1 hour after
      injection compared with placebo-treated patients (48/76 [63%] vs 13/40 [33%],
      respectively; P = .004). CONCLUSION: Across an 8-hour work shift, sumatriptan was
      superior to placebo in reducing productivity loss due to migraine.

PMID- 10943232
TI  - Increasing use of bronchoscopic needle aspiration to diagnose small cell lung
      cancer.
AB  - OBJECTIVE: To review pathology reports to determine whether a temporal change in
      diagnostic procedures that included bronchoscopic needle aspiration (BNA) in
      evaluation of small cell lung cancer (SCLC) had occurred. METHODS: A
      retrospective review of the computerized pathology database of the Wake Forest
      University Baptist Medical Center from 1990 to 1998 was performed. All pathology
      reports of patients newly diagnosed with SCLC were reviewed and abstracted.
      RESULTS: The number of patients newly diagnosed with SCLC during the 9-year study
      period totaled 277. Of these, 173 underwent bronchoscopy. From January 1990 to
      December 1991, 32% (8/25) of bronchoscopies done in patients with SCLC included
      BNA compared with 81% (120/148) (P < .001) from January 1992 to December 1998. In
      addition to the increased use of BNA in patients with SCLC undergoing
      bronchoscopy, the overall diagnostic yield for BNA in SCLC significantly
      increased over the 9-year study period from 50% (4/8) in 1990 and 1991 to 88%
      (106/120) thereafter (P = .001). Overall sensitivity of BNA during bronchoscopy
      was 86% for SCLC with only a small increase in sensitivity with use of all
      procedures (including BNA) to 91%. The use of forceps biopsy and bronchial
      brushings decreased over this period. CONCLUSION: With progressive experience
      with BNA, the frequency of its performance and its diagnostic yield in patients
      with SCLC increased markedly. The SCLC yield may be a worthwhile marker of BNA
      program development.

PMID- 10943231
TI  - Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in
      patients with atrial fibrillation referred for atrioventricular ablation.
AB  - OBJECTIVE: To determine the frequency of tachycardia-related cardiomyopathy in
      patients with atrial fibrillation and systolic dysfunction referred for
      atrioventricular node ablation. PATIENTS AND METHODS: This prospective
      multicenter cohort study was conducted at 16 tertiary care centers. The ejection
      fraction was measured before and 3 and 12 months after atrioventricular node
      ablation. Patients with reduced systolic function (ejection fraction < or = 45%)
      before atrioventricular ablation were included in this study. Patients whose
      ejection fraction increased by at least 15 percentage points and to higher than
      45% were considered to have tachycardia-related cardiomyopathy. RESULTS: Of 63
      patients with systolic dysfunction, 48 had at least 1 adequate follow-up
      echocardiographic study. Sixteen (25%) of the 63 had marked improvement in the
      ejection fraction (mean +/- SD change, 27 +/- 8 percentage points) to a value
      higher than 45% after ablation. CONCLUSIONS: Tachycardia-related cardiomyopathy
      is common in patients with atrial fibrillation and systolic dysfunction referred
      for atrioventricular node ablation. This diagnosis should be considered in all
      patients in whom systolic dysfunction occurs subsequent to or concomitant with
      onset of atrial fibrillation.

PMID- 10943233
TI  - Concurrence of inflammatory bowel disease and multiple sclerosis.
AB  - OBJECTIVES: To quantify the coexistence of inflammatory bowel disease (IBD) and
      multiple sclerosis (MS) and to characterize the diseases when they coexist.
      PATIENTS AND METHODS: In this retrospective study of medical records spanning
      1950 through 1995, the diagnoses of Crohn disease (CD), ulcerative colitis (UC),
      and MS were based on review of inpatient and outpatient records by a
      gastroenterologist and a neurologist. RESULTS: We identified 4 residents of
      Olmsted County, Minnesota, with IBD (3 UC, 1 CD) who had concurrent, clinically
      definite MS; all had mild neurologic disease with little disability. These
      comprised 1% of the IBD and 1.8% of the MS cohort. The CD patient had undergone
      terminal ileal resection; of the UC patients, 2 had pancolitis, and 1 had
      proctosigmoiditis. The observed prevalence of MS at onset of IBD was 3.7 times
      the expected (95% confidence interval, 0.8-10.8). We also reviewed the records of
      32 referral patients with both diagnoses. Disability from MS was moderate at
      median follow-up of 8.5 years. By 15 years, ambulation was impaired in most
      patients. Neurologic disability was similar between patients with CD and UC.
      CONCLUSIONS: Concurrence of the 2 diseases was greater than expected. Although MS
      and IBD may share common predisposing factors, not enough information is
      available to speculate about possible mechanisms.

PMID- 10943234
TI  - Results of direct percutaneous endoscopic jejunostomy, an alternative method for
      providing jejunal feeding.
AB  - OBJECTIVE: To assess the results of direct percutaneous endoscopic jejunostomy
      (DPEJ) as a method for jejunal feeding. PATIENTS AND METHODS: We conducted a
      retrospective study of all patients who were referred for DPEJ between October
      1998, when the procedure was implemented at our institution, and January 2000.
      Medical records were reviewed to assess technical success, complications, and the
      need for repeat procedures. Patient satisfaction with DPEJ was also evaluated by
      means of standardized telephone interviews. RESULTS: In 26 (72%) of 36 patients,
      DPEJ placement was successful. During the mean follow-up of 107 days, none of the
      patients with DPEJ required reintervention for tube malfunction or displacement.
      Two patients developed a persistent enterocutaneous fistula following the removal
      of the DPEJ tube. No other procedure-related complications were noted. Fifteen
      (78%) of 19 patients who responded to follow-up questions reported an overall
      satisfaction rating of 8 or higher on a 10-point scale (1, completely
      dissatisfied, to 10, completely satisfied). CONCLUSIONS: We conclude that DPEJ is
      an effective and safe method for providing jejunal tube feeding. A low
      reintervention rate along with high patient satisfaction makes DPEJ an attractive
      alternative to the more commonly placed jejunostomy feeding tubes.

PMID- 10943235
TI  - Gulf War illnesses: causes and controversies.
AB  - Numerous studies investigating Gulf War illnesses have documented that, while
      Gulf War veterans are no more likely to die or be hospitalized, they complain of
      more symptoms than their non-Gulf War counterparts and are more likely to seek
      medical treatment and disability retirement. Proposed causes include exposure to
      chemical and microbiological agents and psychological factors. No definitive
      evidence has emerged to link chemical exposures to these illnesses, although
      epidemiological studies and animal research suggest possible synergistic effects
      to multiple exposures. Microbiological agents are unlikely to be etiologic.
      Psychological and cultural factors undoubtedly contribute to a number of
      illnesses, but their exact role requires further study. Based on a review of the
      scientific and popular literature, it is reasonable to conclude that Gulf War
      illnesses remain a poorly defined group of symptom clusters. Well-controlled
      research from independent groups is required to answer the numerous questions
      that have arisen from this illness outbreak.

PMID- 10943236
TI  - Gerty Cori--Nobel laureate in medicine or physiology.

PMID- 10943237
TI  - Prevention and treatment of osteoporosis in women with breast cancer.
AB  - Women who have had breast cancer may be at higher risk for osteoporosis than
      other women. First, they are more likely to undergo early menopause, due to
      chemotherapy-induced ovarian failure or oopherectomy. In addition, chemotherapy
      may have a direct adverse effect on bone mineral density (BMD), and osteoclastic
      activity may increase from the breast cancer itself. While estrogen therapy is
      considered standard for the prevention and treatment of osteoporosis, use of
      estrogen in women with a history of breast cancer is usually contraindicated. The
      approach to osteoporosis in women with breast cancer is also affected by the use
      of tamoxifen in many, as this drug appears to have opposite effects on BMD in
      premenopausal and postmenopausal women. We have reviewed therapeutic alternatives
      for the prevention and treatment of osteoporosis, focusing on patients with a
      history of breast cancer. Alendronate and raloxifene are currently approved in
      the United States for the prevention of osteoporosis; alendronate, raloxifene,
      and calcitonin are approved for treatment. Alendronate has the greatest positive
      effect on BMD and reduces the incidence of vertebral and nonvertebral fractures.
      Raloxifene and calcitonin appear to reduce the incidence of vertebral fractures;
      their effects on the incidence of nonvertebral fractures are not yet proven.
      Although no published studies specifically address the use of these approved
      agents for osteoporosis in women with breast cancer, understanding their relative
      effects on BMD in postmenopausal women in general will facilitate therapy
      selection in this population. Postmenopausal women with a history of breast
      cancer should undergo bone mineral analysis. Normal results and absence of other
      risk factors ensure that calcium and vitamin D intake are adequate. If osteopenia
      or other risk factors are present, preventive therapy with alendronate or
      raloxifene should be considered. For osteoporosis, treatment with alendronate
      should be strongly considered. Raloxifene and calcitonin are alternatives when
      alendronate is contraindicated. Further studies are needed to evaluate the
      optimal timing of initial bone mineral analysis in premenopausal women after
      breast cancer diagnosis and to determine the value of preventive treatment in
      women scheduled to undergo chemotherapy.

PMID- 10943239
TI  - Herbal therapy: what a clinician needs to know to counsel patients effectively.
AB  - The use of herbal medicine in the United States has been increasing at a steady
      pace over the past decade. Most recent estimates suggest that the US population
      spends $5 billion per year for herbal supplements alone. Herbal supplements are
      receiving increasing exposure through national media, in lay journals, and more
      recently in the scientific press. Interest in herbal medicine has been
      facilitated by multiple factors, including the perception that pharmaceutical
      medications are expensive, overprescribed, and often dangerous. Alternatively,
      herbal medicine is often perceived as being "natural" and is therefore considered
      safe. While the growth of the herbal medicine industry in the United States can
      probably not continue at this accelerated pace indefinitely, there is little
      indication of any major slowing. Therefore, patients will continue to use herbal
      medications. Knowledge of these preparations (including their potential benefits
      and risks as well as their ability to interact with pharmaceutical medications)
      will enable physicians to provide a balanced and objective view to patients
      seeking information on herbal therapy.

PMID- 10943238
TI  - Gene therapy for atherosclerotic cardiovascular disease: a time for optimism and
      caution.
AB  - Cardiovascular disease is the leading cause of death in the Western world, and
      gene therapy approaches to several cardiovascular disorders have been proposed.
      One of the major stumbling blocks to be overcome before widespread clinical use
      of this technology is how to deliver DNA efficiently and safely to cells in vivo.
      While delivery of DNA alone is inefficient, use of viral vectors may overcome
      this problem. Adenoviral vectors are most commonly used in cardiovascular gene
      delivery, but toxicity related to these vectors remains a concern. In addition,
      duration of gene expression with use of these vectors is limited, which may be
      advantageous in settings in which transient expression is satisfactory to obtain
      a therapeutic effect. Gene therapy has been suggested as an approach to multiple
      conditions, including restenosis after angioplasty, therapeutic
      neovascularization, and bypass graft restenosis. Phase 1 clinical trials were
      recently reported. While proof of principle has been established in preclinical
      animal models, convincing efficacy data in humans do not yet exist. Improvements
      in vector technology and methods of catheter-mediated vascular gene delivery are
      needed before widespread clinical application of this therapy.

PMID- 10943240
TI  - Recalcitrant pyoderma gangrenosum treated with thalidomide.
AB  - Pyoderma gangrenosum is a painful, noninfectious, ulcerating skin disorder often
      associated with systemic disease. Thalidomide has been used to treat many
      inflammatory dermatologic conditions and has been reintroduced in the United
      States to treat immune-modulated diseases such as pyoderma gangrenosum. The
      patient described, a 47-year-old man, had histologically confirmed pyoderma
      gangrenosum that did not respond to treatment with several courses of
      methylprednisolone. The ulcer healed with 10 weeks of oral thalidomide
      administration.

PMID- 10943241
TI  - Brugada-type electrocardiographic pattern induced by cocaine.
AB  - Right bundle branch block with coved ST-segment elevation in leads V1 through V3
      is the electrocardiographic (ECG) marker of the Brugada syndrome. We describe a
      healthy young man with a normal baseline ECG in whom a transient Brugada pattern
      was observed repeatedly after recreational cocaine use. Intravenous
      administration of procainamide and subsequent intravenous propranolol followed by
      noradrenaline failed to reproduce the Brugada sign. An electrophysiologic study
      performed in the presence of the Brugada ECG pattern showed no inducible
      arrhythmias. This case illustrates that, in susceptible individuals, cocaine may
      provoke the Brugada sign. The clinical importance of this cocaine-induced ECG
      abnormality is currently unknown.

PMID- 10943242
TI  - Recurrent lumbar ependymoma presenting as headache and communicating
      hydrocephalus.
AB  - We describe a patient with a recurrent spinal cord ependymoma who initially
      presented with symptoms of increased intracranial pressure rather than symptoms
      directly relating to involvement of the conus medullaris. Brain magnetic
      resonance imaging with gadolinium showed communicating hydrocephalus. Magnetic
      resonance imaging of the entire spinal cord with gadolinium revealed recurrent
      tumor. Postoperatively, a permanent ventriculoperitoneal shunt was placed.
      Recognition of the association between spinal cord ependymoma and hydrocephalus
      is important in the evaluation of patients with headache.

PMID- 10943243
TI  - Autoimmune hemolytic anemia in a patient with autosomal dominant chronic
      mucocutaneous candidiasis.
AB  - Chronic mucocutaneous candidiasis is a heterogeneous immunodeficiency syndrome
      characterized by recurrent candidal infections of the skin, nails, and mucous
      membranes. The syndrome can be associated with autoimmune conditions, especially
      endocrine disorders. Typically, inheritance is autosomal recessive, and abnormal
      T-cell-mediated immunity is thought to be the underlying deficit. We describe a
      27-year-old man with chronic mucocutaneous candidiasis inherited in an autosomal
      dominant fashion, in whom both lymphocyte blastogenesis and delayed-type skin
      reactivity to Candida antigens were normal. Notable features of the case include
      autoimmune hemolytic anemia, probable hypoparathyroidism, and hypogonadal
      hypogonadism.

PMID- 10943244
TI  - Meningeal involvement in Wegener granulomatosis.
AB  - We describe 2 cases and review the literature on the spectrum of clinical
      manifestations associated with meningeal involvement in patients with Wegener
      granulomatosis (WG). A 31-year-old man and a 60-year-old woman with WG in
      complete clinical remission developed severe chronic headaches. No inflammatory
      activity was detectable at sites of previous disease activity, and nonspecific
      markers of inflammation were within normal limits. However, both patients had
      persistently elevated titers of antineutrophil cytoplasmic antibodies
      (cytoplasmic staining pattern). Cerebrospinal fluid examinations showed no
      abnormalities that suggested inflammation, infection, or malignancy. Head
      magnetic resonance imaging with gadolinium contrast revealed enhancement of the
      dura in both patients, and a meningeal biopsy in 1 patient confirmed active WG.
      Both patients' symptoms resolved after reinstitution of aggressive
      immunosuppressive therapy.

PMID- 10943245
TI  - 22-year-old woman with severe microcytic anemia.

PMID- 10943246
TI  - Recertifying in the art of medicine: what I would tell young physicians.

PMID- 10943247
TI  - Successful extubation with use of C1 esterase inhibitor concentrate in a patient
      with hereditary angioedema.

PMID- 10943248
TI  - Inherited thrombophilia, hypercoagulability, and risk factors for
      atherosclerosis.

PMID- 10943249
TI  - Physostigmine treatment of gamma-hydroxybutyric acid overdose: appropriate or
      inappropriate use of a reversal agent?

PMID- 10943250
TI  - Physostigmine treatment of gamma-hydroxybutyric acid overdose: appropriate or
      inappropriate use of a reversal agent?

PMID- 10943251
TI  - Prevalence and health consequences of stalking--Louisiana, 1998-1999.

PMID- 10943252
TI  - Progress toward poliomyelitis eradication--European region, 1998-June 2000.

PMID- 10943253
TI  - Hepatitis C virus infection among firefighters, emergency medical technicians,
      and paramedics--selected locations, United States, 1991-2000.

PMID- 10943254
TI  - Use of FDA-approved pharmacologic treatments for tobacco dependence--United
      States, 1984-1998.

PMID- 10943255
TI  - Outbreak of aseptic meningitis associated with multiple enterovirus serotypes-
      Romania, 1999.

PMID- 10943256
TI  - Neonatal skin care.
AB  - The relative importance of neonatal health and neonatal skin care has been
      highlighted in recent years as infant mortality rates have decreased while death
      rates during the neonatal period remain unacceptably high in many areas of the
      world. During the neonatal period, many newborns develop preventable, clinically
      apparent skin problems, and many more, especially preterm neonates, experience
      morbidity caused by compromised skin barrier integrity. Several strategies are
      available for protecting the integrity and promoting the hygiene of the skin and
      augmenting its function as a barrier to TEWL and heat loss and the entrance of
      infectious or toxic agents. Research defining optimal applications of many of
      these strategies, however, and the development of new approaches in skin care is
      one of the greatest challenges in pediatric dermatology and holds promise for
      improving neonatal outcome in the future. The ability to modulate epidermal
      barrier function and integrity relies largely on the topical use of protective
      materials and substances and manipulation of the external environment. As
      understanding of epidermal barrier development advances, perhaps pharmacologic
      manipulation of barrier development, as now practiced for augmentation of
      neonatal lung maturity, will become a reality. In the meantime, greater awareness
      among neonatal health care practitioners of state-of-the-art strategies for
      optimizing skin integrity in neonates is an important step toward improving
      neonatal health.

PMID- 10943257
TI  - Vascular and pigmented birthmarks.
AB  - Vascular and pigmentary lesions compromise most birthmarks. Lesions range from
      uncommon, to very common, some being essentially normal variants. The natural
      history of these varies from being transient phenomena of no significance to
      permanent cutaneous findings that may be associated with significant systemic
      complications or diseases. This article describes the most frequently encountered
      clinically important birthmarks, including congenital nevi, hypopigmented
      lesions, vascular malformations and hemangiomas, discussing clinical
      presentation, diagnosis, and findings that should prompt early assessment and
      treatment.

PMID- 10943258
TI  - Cutaneous signs of neural tube dysraphism.
AB  - Cutaneous markers have a crucial role in the detection and diagnosis of occult
      neural tube dysraphism. Recognition of these stigmata and appropriate radiologic
      imaging decrease the long-term morbidity of this condition.

PMID- 10943259
TI  - Dermatologic clues to inherited disease.
AB  - Genetic diseases often have cutaneous manifestations, which can be the first or
      most prominent signs of the underlying problem. Recognition of these dermatologic
      clues allows prompt diagnosis and intervention. In this article, the authors have
      attempted to outline several important examples of genodermatoses.

PMID- 10943260
TI  - Managing acne in adolescents.
AB  - Acne is the most common skin disorder affecting adolescents. Although no cure
      exists for acne, most patients benefit from currently available medications, and
      most can be managed effectively by their primary care providers. By offering this
      care, pediatricians can reduce the emotional burden of acne and help to prevent
      the permanent scarring so commonly seen in the past.

PMID- 10943261
TI  - Office-based treatment of pediatric skin disease.
AB  - This article is divided into three sections. The first is a selected review of
      important points that will enhance practitioners' treatment or approach to many
      of the disorders covered in depth elsewhere in this issue. It is hoped that this
      will reduce the reliance on specialists in the current managed care environment.
      The second section deals with "truisms for a happy practice." These should help
      practitioners of any specialty, field, or service industry who deal with parents
      and children. The final section is devoted to information management and what is
      available to practitioners to enhance their knowledge and the knowledge of their
      patients.

PMID- 10943262
TI  - Topical therapies and medications in the pediatric patient.
AB  - Topical medications and therapies are necessary for the proper management of skin
      diseases in children; however, physicians must be aware of the differences in
      percutaneous absorption and the risks for toxicity from topical medications,
      which are often unique to infants and children. Topical therapy must be
      individualized, and success often depends on proper vehicle selection, ease of
      application, and cost to patients and their families. Although many commercially
      available topical therapies are not FDA approved for use in children, recently
      enacted legislation has served to stimulate much-needed drug research in
      pediatric patients. New therapies on the horizon, such as tacrolimus, may prove
      to be equally efficacious and less toxic.

PMID- 10943263
TI  - Atopic dermatitis in infants and children. An update.
AB  - The goal in treating patients with atopic dermatitis is to maintain adequate
      hydration while decreasing pruritus and inflammation. It is also important to
      recognize factors that are responsible for flares. Although the etiology of
      atopic dermatitis remains unknown, therapies are being developed targeting
      immunologic defects in this disease.

PMID- 10943264
TI  - Allergic contact dermatitis.
AB  - Allergic contact dermatitis (ACD) in children is underrecognized. It is often
      confused with antibody-mediated allergies such as urticaria or allergic rhinitis,
      but the mechanism in ACD involves T lymphocytes and not antibody. Surprisingly,
      sensitization to common allergens is likely to occur in infancy. All contact
      allergens are weak allergens requiring repeated exposure over long periods of
      time. Detection of specific allergens is by epicutaneous (patch) testing and will
      provide the basis for allergen avoidance therapeutic strategies.

PMID- 10943265
TI  - Diaper dermatitis.
AB  - The primary goals of preventing and treating diaper dermatitis include keeping
      the skin dry, protected, and infection free. Frequent diaper changes with the
      superabsorbent disposable diapers may be the best tactic for infants' skin, if
      not the environment. Also, the more time that infants spend without diapers, the
      less dermatitis they experience, but a practical balance must be struck. Gentle
      cleansing and barrier creams are beneficial, and candidal infection must be
      treated. Finally, any recalcitrant diaper dermatitis must be further investigated
      to uncover underlying disease (Fig. 6).

PMID- 10943266
TI  - Infestations in the pediatric patient.
AB  - This article specifically focuses on arthropods that act as ectoparasites to the
      human host. A cutaneous eruption caused by the larvae of roundworms is briefly
      discussed.

PMID- 10943267
TI  - Pediatric skin tumors.
AB  - This article summarizes several malignant childhood neoplasms and benign tumors
      that can mimic malignancies. Because malignant skin tumors are rare in children,
      parents and physicians often are not sufficiently suspicious to ensure that an
      early diagnosis can be made. Many malignant skin tumors have features that
      suggest a vascular or hemangioma-like lesion. Because hemangiomas occur in 10% of
      infants, it is often considered prudent to adopt a wait-and-see attitude;
      however, if the lesion is too firm to be a hemangioma or its growth pattern does
      not follow that of a typical hemangioma, additional options should be considered.
      To manage childhood skin malignancies, one needs expert consultation, early
      biopsy, and correct histopathologic interpretation.

PMID- 10943268
TI  - The Swedish Two-County Trial twenty years later. Updated mortality results and
      new insights from long-term follow-up.
AB  - The benefit of invitation to mammographic screening observed in this trial is
      maintained as a highly significant 32% reduction in breast cancer mortality.
      Mammographic screening for breast cancer continues to save lives after up to 20
      years. Screening derives this benefit by improving the distribution of tumors
      diagnosed with respect to prognostic categories based on node status, size, and
      histology of tumors. There is potential for modern screening programs with
      shorter interscreening intervals to achieve even greater improvements in
      prognostic category and greater reductions in breast cancer mortality.
      Mammography can discriminate a subpopulation of high-risk cases, those displaying
      casting-type calcifications on the mammogram, among very small tumors, with
      fundamental implications for diagnosis and treatment.

PMID- 10943270
TI  - Imaging of breast masses.
AB  - The American College of Radiology Breast Imaging and Reporting Data System (ACR
      BI-RADS) defines a mass as a space-occupying lesion seen in at least two
      projections. This article focuses on the management of breast masses with
      mammography and ultrasonography. Recommended work-up pathways are modified for
      nonpalpable masses, palpable masses in women over the age of 30, and palpable
      masses in women under the age of 30. The suggested protocols are based on
      scientific peer-reviewed literature whenever possible, but when evidence based
      studies are not available, the author relies on expert opinion.

PMID- 10943269
TI  - Ductal carcinoma in situ. Implications for screening mammography.
AB  - Ductal carcinoma in situ (DCIS) now represents 20% of all newly diagnosed breast
      cancers because of increased detection by screening mammography. Twenty year
      relative survival rates are 97%. Postsurgical and histological studies and recent
      molecular biological studies indicate that most cases of DCIS will progress to
      invasive carcinoma if not detected by mammography. Screening mammography studies
      support the need for annual versus less frequent screenings to detect DCIS before
      further progression.

PMID- 10943271
TI  - Successful methods to reduce false-positive mammography interpretations.
AB  - Several approaches to mammographic interpretation and breast imaging management
      have been developed that substantially reduce the frequency of false-positive
      cases, involving both recall examinations and biopsies, without meaningfully
      reducing the detection of nonpalpable favorable-prognosis cancers. By applying
      these approaches successfully, on a nationwide scale, radiologists should be able
      to demonstrate convincingly that the benefits of mammography far outweigh the
      risks of false-positive interpretations. The challenge we face is to learn to use
      the approaches effectively, thereby achieving widespread use.

PMID- 10943272
TI  - Optimizing techniques in screen-film mammography.
AB  - This article provides a practical approach to the steps needed to optimize
      mammography techniques. Those steps consist of a series of activities that begin
      with the choice of mammography film, then choosing the optimum film processing
      for that film type, selecting the appropriate technique factors for exposure, and
      the proper viewing of processed mammography films. In each area, the basic
      physics underlying film and film processing, mammography equipment performance,
      image contrast, and image display, are used to determine optimized mammography
      techniques.

PMID- 10943273
TI  - Double reading.
AB  - Clearly, the cost of double reading varies with the approach used. The
      Massachusetts General Hospital method can only lead to an increase in recalls and
      the costs that these engender (anxiety for the women recalled, trauma from any
      biopsies obtained, and the actual monetary costs of additional imaging and
      interventions). It is of interest that one potential cost, the concern that women
      recalled may be reluctant to participate again in screening, does not seem to be
      the case. Women who are recalled appear to be more likely to participate in
      future screening. Double interpretation where there must be a consensus between
      the interpreting radiologists, and if this cannot be reached a third arbiter, is
      the most labor intensive, but can reduce the number of recalls in a double
      reading system. Computer systems have been developed to act as a second reader.
      The films must be digitized and then fed through the reader, but studies suggest
      that the computer can identify cancers that may be overlooked by a human reader.
      The challenge is to do this without too many false-positive calls. If the
      radiologist finds the false-positives are too numerous and distracting, then the
      system is not used. As digital mammographic systems proliferate, and computer
      algorithms become more sophisticated, the second human reader will likely be
      replaced by a computer-aided detection system and double reading will become the
      norm.

PMID- 10943274
TI  - Computer-aided detection and diagnosis of breast cancer.
AB  - The limitations of radiologists when interpreting mammogram examinations provides
      a reasonable, if not compelling, basis for application of computer techniques
      that have the potential to improve diagnostic performance. Computer algorithms,
      at their present state of development, show great promise for clinical use. It
      can be expected that such use will only improve as computer technology and
      computer methods continue to become more formidable. The eventual role of
      computers in mammographic detection and diagnosis has not been fully defined, but
      their effect on practice may one day be very significant.

PMID- 10943275
TI  - False-negative mammograms. Medical, legal, and risk management implications.
AB  - From a strictly biologic perspective, delay in diagnosis of breast cancer is
      axiomatic. The number of cell divisions that must occur before detection is
      possible by either clinical or mammographic methods means that a finite time has
      occurred in which the outcome for any given case may have already been
      determined. That early detection and diagnosis of breast cancer lead to improved
      survival may be intuitive, but clinical trials have been necessary to validate
      the concept. Delay in diagnosis is unavoidable but the period of delay may be
      lessened in many cases, prompting earlier intervention and impacting outcomes.
      Mammography is an important vehicle for such earlier intervention and the issue
      of the false-negative mammogram is of concern to the radiology community, the lay
      community, and the courts. Mammographic interpretation has not yet approached a
      sufficiently standardized benchmark. Detection and diagnosis are dependent on a
      series of factors that need to be integrated to achieve the dual goals of timely
      intervention for bonafide purposes and reduction of unnecessary procedures and
      interventions. Some of the reasons for delay in diagnosis are unavoidable,
      beginning with the absence of clinical or imaging features of malignancy and
      extending to limitations of sufficiently specific features to prompt
      intervention. On the other hand, other reasons are avoidable and attention to
      many of these causes should lessen the incidence of such delay. Regardless of the
      reason, those women who feel that their breast cancer should have been diagnosed
      at an earlier time may consider subjecting their mammographic studies to
      independent reviews. At such a point, the precise reasons for delay may be better
      analyzed, all in an attempt to provide an adequate reconciliation of what has
      come to be known as the false-negative mammogram.

PMID- 10943276
TI  - The Mammography Quality Standards Act. An overview of the regulations and
      guidance.
AB  - The MQSA has imposed a set of federal regulations on every facility and
      radiologist that performs or interprets mammograms. Because annual inspections
      and paperwork are somewhat burdensome, many hope that in the future the process
      of FDA inspections might be streamlined for facilities with good track records
      and few, if any, findings at inspection. This would serve to reduce facility
      inconvenience and the costs of regulatory compliance without compromising patient
      care and outcomes. Currently, however, although not all personnel are required to
      be familiar with the regulations, key individuals should be conversant with the
      rules, FDA guidance, and methods that the facility has devised to comply with the
      regulations.

PMID- 10943277
TI  - Equipment, technique, quality assurance, and accreditation for imaging-guided
      breast biopsy procedures.
AB  - Needle biopsy diagnosis of breast lesions can be performed using fine needle
      aspiration or large core needle biopsy techniques. Imaging guidance using
      mammographic stereotactic devices or sonography can accurately guide biopsy
      probes into suspicious lesions. Choice of the biopsy probe in any individual
      patient will depend upon equipment availability, lesion characteristics, breast
      configuration, and cost considerations. Quality control and quality assurance
      programs should be instituted to maintain a high level of patient care.
      Facilities performing these biopsies can obtain accreditation to attest to the
      quality of their biopsy program.

PMID- 10943278
TI  - Clinical management issues in percutaneous core breast biopsy.
AB  - Percutaneous imaging-guided core biopsy is a less invasive and less expensive
      alternative to surgical biopsy for the evaluation of breast lesions. Percutaneous
      core biopsy is most often used for evaluation of BI-RADS category 4 lesions, but
      may also be helpful in the evaluation of some BI-RADS category 5 lesions.
      Stereotactic guidance is particularly useful for calcifications; for masses that
      can be seen with ultrasound, ultrasound guidance may be preferable because of the
      absence of radiation and lower cost. The automated core biopsy needle is
      excellent for mass lesions, but directional vacuum-assisted biopsy is superior
      for calcifications. Directional vacuum-assisted biopsy may also be preferable for
      small lesions that may require placement of a localizing clip and lesions that
      are superficial or in thin breasts. The more expensive ABBI device has
      substantial limitations, and its role in percutaneous breast biopsy has not been
      demonstrated. Complete removal of the mammographic target can occur at
      percutaneous biopsy, and is a more frequent event when the larger tissue
      acquisition devices are used. Complete removal of the mammographic target does
      not ensure complete excision of the histologic process. Further investigation is
      necessary to determine in which lesions, if any, complete removal of the target
      is advantageous. Epithelial displacement can occur during all breast needling
      procedures, but may be less frequent at directional vacuum-assisted biopsy than
      at fine-needle aspiration or automated core biopsy. There is no evidence that
      displaced cells are of biologic significance, but displaced DCIS can mimic
      infiltrating carcinoma. The pathologist should be aware of the findings of
      epithelial displacement, to avoid misdiagnosing DCIS as infiltrating ductal
      carcinoma. Some lesions warrant repeat biopsy or surgical excision after
      percutaneous core biopsy. Repeat biopsy is warranted if histologic findings and
      imaging findings are discordant. Surgical excision is warranted for lesions
      yielding a percutaneous diagnosis of ADH or possible phyllodes tumor. Controversy
      exists regarding the need for surgical excision after percutaneous diagnosis of
      radial scar, papillary lesion, ALH, or LCIS. Follow-up is necessary if
      percutaneous biopsy yields benign findings concordant with imaging
      characteristics. Follow-up protocols vary, but all require substantial commitment
      of time and resources. We have an embarassment of riches for performing
      percutaneous core biopsy of the breast. It can be estimated that approximately 1
      million breast biopsies will be performed this year to diagnose approximately
      200,000 breast cancers. Percutaneous core biopsy may spare many of these women
      the need for a more deforming, invasive, and expensive surgical biopsy. Further
      work is necessary to optimize criteria for patient selection, develop and define
      the role of new technologies for tissue acquisition, refine protocols for
      management after percutaneous breast biopsy, and assess long-term outcome, so
      that more women can benefit from this minimally invasive approach to breast
      diagnosis.

PMID- 10943279
TI  - Identification of the sentinel node in patients with breast cancer.
AB  - Sentinel node analysis represents a significant advance in the diagnosis and
      treatment of invasive breast cancer. The traditional crude method of full
      axillary dissection for assessing the status of the axillary nodes can now be
      discarded in favor of the much more elegant and modern approach of minimally
      invasive sentinel node analysis and its attendant elimination of the morbidity of
      traditional axillary node dissection. The many impediments to and pitfalls in the
      technique of sentinel node analysis, however, must be recognized and overcome for
      the procedure to be reliable and consistently successful. The use of ultrasound
      and a smaller particle size can help overcome many of these pitfalls. Because
      ultrasound identification of the axillary sentinel node in patients with invasive
      breast cancer is possible, it may allow for percutaneous excision of these nodes
      in the future (Fig. 8). Combining percutaneous excision and ablation of the
      primary breast carcinoma with percutaneous excision of the sentinel node allows
      for the nonsurgical treatment of small breast cancers in the future. The modern
      breast radiologist should be at the forefront of these advances.

PMID- 10943281
TI  - Economic challenges in breast imaging. A survivor's guide to success.
AB  - Most breast imaging centers today operate under financial strain. Among
      strategies designed to improve their bottom line, more efficient use of the
      radiologist's time is the most fundamental strategy and the one most likely to
      succeed in all breast imaging centers. Tasks performed by the radiologist that
      are not directly related to interpretation and consultation should be shifted to
      other personnel. Other strategies that may help some breast imaging centers
      include accepting only self-paying patients, renegotiating the hospital contract,
      performing more interventional procedures, and extending the hours of operation.
      Measures that can improve the economic efficiency of screening mammography
      include batch interpretation of mammograms; paperwork reduction; brief automated
      reports; limiting requests for previous films from other facilities to only
      potentially necessary cases; dedicated screening mammography examination rooms;
      reduction in recall rates; and, in certain circumstances, extension of breast
      center hours. Measures that can improve the economic efficiency of diagnostic
      mammography performance and interpretation include dedicated diagnostic
      mammography examination rooms, automated film rotators, improved scheduling, and
      efficient work-flow patterns for examination performance. Measures that can
      improve the economic efficiency of both screening and diagnostic mammography
      include improved triage of screening and diagnostic patients, reminder telephone
      calls to confirm mammography appointments, greater use of medical assistants to
      help the radiologists and technologists, and streamlined film library procedures
      and operations. Measures that can improve the economic efficiency of breast
      interventional procedures include preprocedure work-up, establishment of
      scheduling protocols, and greater involvement of technologists and medical
      assistants in assisting the radiologist who performs the interventional
      procedures. All of these methods are intended to create a breast imaging center
      that is cost efficient while maintaining a patient-friendly atmosphere and
      diagnostic accuracy.

PMID- 10943280
TI  - An introduction to economic issues in breast imaging.
AB  - Marked increases in national health care costs, along with governmental coverage
      of health care costs for the elderly under Medicare, have resulted in increased
      government regulation of medical reimbursement rates. Private insurers and HMOs
      now provide reimbursements that are frequently the same or lower than those from
      Medicare. Reimbursement rates for mammography have been particularly restricted.
      Although screening mammography appears to be as cost-effective as other commonly
      accepted medical interventions, some third-party payors have been reluctant to
      reimburse screening mammography because of its perceived effect on overall health
      care costs. An objective analysis shows that inclusion of coverage for screening
      mammography, however, even beginning at age 40 years, has only a slight effect on
      total health care costs. Adequate reimbursement for screening mammography
      supports an effort that provides substantial reduction in deaths from breast
      cancer.

PMID- 10943282
TI  - The breast imaging center. Successful management in today's environment.
AB  - Radiologists, because of their expertise in mammography and other diagnostic and
      imaging tests, are assuming an increasing role in the diagnosis of breast cancer,
      but are faced with decreasing reimbursements and a shortage of trained
      mammographers. Delegation of many physicians' tasks to nonphysician employees is
      more cost-effective. Reimbursements must be increased to support radiologists in
      their expanded role.

PMID- 10943283
TI  - Digital mammography, sestamibi breast scintigraphy, and positron emission
      tomography breast imaging.
AB  - Digital mammography allows for the separate optimization of image acquisition and
      display. Through this technology, and the application of image processing and
      computer aided diagnosis, breast cancer detection and breast lesion diagnosis
      might be improved. Besides the obvious data storage, retrieval, and transmission
      advantages that digital mammography will allow, additional advances such as
      tomosynthesis, dual energy mammography and digital subtraction mammography are in
      development. The possible future utility of Sestamibi breast scintigraphy and
      breast imaging with positron emission tomography is also discussed.

PMID- 10943284
TI  - Screen-film and digital mammography. Image quality and radiation dose
      considerations.
AB  - Factors affecting image quality and patient dose in screen-film and digital
      mammography have been discussed. Some proposed parameters for judging image
      quality and breast exposure measurements and dose calculations relating to
      changes in image quality factors have been reviewed. It is important to remember
      that the goal in making a mammogram is to obtain as much diagnostic information
      as possible at the lowest dose compatible with that information. As noted
      previously, this necessitates compromises (i.e., an optimization of factors that
      affect image quality). These include beam quality, compression, imaging geometry,
      grids, receptor characteristics, processing of the film or digital image, and
      display and viewing conditions. If this is done correctly, a high-quality
      mammogram can be obtained at a reasonably low dose to the patient. The goal is
      not simply to use as low a dose as possible, because if this is done there is a
      large risk of degrading the performance of mammography in detecting or accurately
      characterizing small, node-negative cancers.

PMID- 10943285
TI  - MR imaging of the breast.
AB  - The results of clinical investigation suggest that MR imaging can provide
      clinically important information that cannot be obtained with conventional
      imaging methods, and that this modality will, in the future, be an invaluable
      adjunctive breast imaging tool just as breast ultrasound is today. MR imaging
      appears to be the most accurate method for the detection of implant failure, and
      although it is the most costly of the available implant imaging techniques, it
      may be the study of choice when there is a question of implant integrity that
      cannot be answered with conventional methods. MR imaging as a method to detect,
      diagnose, and stage breast cancer remains in the investigational stage. The
      specificity of MR imaging appears limited because of the overlap in the
      enhancement kinetics and morphologic appearance of benign and malignant lesions.
      In selected cases, the identification of certain morphologic features, such as
      internal septations or the absence of enhancement, may be used to classify a
      lesion as benign, offering an alternative to percutaneous or excisional biopsy.
      MR imaging appears to be very sensitive for the visualization of both invasive
      carcinoma and DCIS. Perhaps most important, MR imaging can detect invasive and
      noninvasive breast carcinoma that is both mammographically and clinically occult,
      offering the potential for more accurate breast cancer staging and optimized
      treatment planning. MR imaging is emerging as perhaps the most promising imaging
      modality for breast cancer detection to date. Published results, however, are
      from studies with relatively small numbers of patients. The results of these
      studies should be validated in a large-scale clinical trial before MR imaging is
      implemented clinically, outside of research settings. This type of clinical
      investigation is needed to define the technical requirements for optimal imaging,
      to define interpretation criteria, to develop accurate MR imaging guided
      localization and biopsy systems, to define the clinical indications for which MR
      imaging should be used as an adjunct to conventional imaging methods, and to
      address the issue of cost-effectiveness. One such trial, an international, multi
      institutional study funded by the National Cancer Institute, is presently
      underway.

PMID- 10943286
TI  - Society of Breast Imaging residency and fellowship training curriculum.
AB  - A recently developed Society of Breast Imaging curriculum for residency training
      is intended to provide guidance to residents and their mentors, and to practicing
      radiologists who want to keep up to date in screening, diagnosis, and
      interventional procedures. The curriculum contains lists of key concepts in 14
      subject areas: epidemiology; anatomy; pathology, and physiology; equipment and
      technique; quality control; interpretation; problem-solving mammography;
      ultrasound; interventional procedures; reporting and medicolegal aspects;
      screening; MR imaging; therapeutic considerations; and patient management
      principles. The curriculum also makes recommendations about residency training,
      including the number of examinations the resident should interpret, and the time
      the resident should spend in breast imaging. Recommendations for fellowship
      training are also discussed.

PMID- 10943287
TI  - Allergen vaccines for specific diagnosis.

PMID- 10943288
TI  - Percutaneous and intracutaneous diagnostic tests of IgE-mediated diseases
      (immediate hypersensitivity).

PMID- 10943289
TI  - In vitro diagnostic tests of IgE-mediated diseases.

PMID- 10943290
TI  - Diagnostic tests for urticaria and angioedema.

PMID- 10943291
TI  - Ocular allergic diseases: differential diagnosis, examination techniques, and
      testing.

PMID- 10943292
TI  - Intranasal disease and provocation.

PMID- 10943293
TI  - Lung disease.

PMID- 10943294
TI  - Food allergy: current diagnostic methods and interpretation of results.

PMID- 10943295
TI  - Determining allergic versus nonallergic drug reactions.
AB  - Drug sensitivity is a major clinical problem that is incompletely understood.
      Much effort continues in identifying patients at risk for developing drug
      sensitivities, predicting the various immune mechanisms most likely to be
      activated by a specific drug, and developing more reliable tests to identify the
      drug-allergic patient.

PMID- 10943296
TI  - Fiberoptic rhinoscopy.

PMID- 10943297
TI  - Diagnostic assessment of otitis media.
AB  - Accurate diagnosis of OM is important but often difficult. To enhance the
      likelihood of accurate diagnosis, pneumatic otoscopy is the preferred method of
      examination generally available to clinicians. Findings by pneumatic otoscopy
      should be coupled with the presence or absence of symptoms and signs to delineate
      a diagnosis of AOM or OME. Tympanometry can be a useful adjunct in the clinical
      assessment of middle ear effusion. Audiometry is particularly important for
      patients with recurrent or chronic middle ear disease.

PMID- 10943298
TI  - Imaging of the upper airway and sinuses.
AB  - Before imaging the sinusitis patient, the clinican needs to establish diagnostic
      goals and be aware of the limitations of imaging. When reviewing imaging studies
      of the paranasal sinuses, the clinician needs a basic understanding of the
      anatomy of the ostiomeatal complex and sinonasal cavity, the common anatomical
      variants, and the typical appearances of inflammatory, infectious, and neoplastic
      etiologies.

PMID- 10943299
TI  - Diagnostic tests for type IV or delayed hypersensitivity reactions.

PMID- 10943300
TI  - Controversial and unproven diagnostic tests for allergic and immunologic
      diseases.

PMID- 10943301
TI  - Interactions between wingless and frizzled molecules in Drosophila.

PMID- 10943302
TI  - The heterotrimeric G protein genes of Caenorhabditis elegans.

PMID- 10943303
TI  - Programmed cell death and its regulation and initiation in C. elegans.

PMID- 10943304
TI  - Presenilin proteins and their function during embryonic development and
      Alzheimer's disease.

PMID- 10943305
TI  - Cell-cell interaction during Drosophila embryogenesis: novel mechanisms and
      molecules.

PMID- 10943306
TI  - The roles of BMPs, BMP antagonists, and the BMP signaling transducers Smad1 and
      Smad5 during dorsoventral patterning of the zebrafish embryo.

PMID- 10943307
TI  - Genetic dissection of heart development.

PMID- 10943308
TI  - Eph receptors and ephrins are key regulators of morphogenesis.

PMID- 10943309
TI  - Eph receptor tyrosine kinases and their ligands in development.

PMID- 10943310
TI  - Embryonic patterning of Xenopus mesoderm by Bmp-4.

PMID- 10943311
TI  - The Indian hedgehog--PTHrP system in bone development.

PMID- 10943312
TI  - Hedgehog signaling in animal development and human disease.

PMID- 10943313
TI  - Vaccination therapy for malignant disease: the clinical perspective.

PMID- 10943314
TI  - Tumor antigens.

PMID- 10943315
TI  - Costimulatory molecules in vaccine design.

PMID- 10943316
TI  - Application of T cell immunotherapy for human viral and malignant diseases.

PMID- 10943317
TI  - Immune monitoring in cancer immunotherapy.

PMID- 10943318
TI  - Retroviral vectors for cancer gene therapy.

PMID- 10943319
TI  - CpG oligonucleotides as immune adjuvants.

PMID- 10943320
TI  - DNA vaccination against cancer antigens.

PMID- 10943321
TI  - Skin cancer--prospects for novel therapeutic approaches.

PMID- 10943322
TI  - The hybrid cell vaccination approach to cancer immunotherapy.

PMID- 10943323
TI  - T cell receptor peptides for the vaccination therapy of multiple sclerosis.

PMID- 10943324
TI  - Regulatory aspects of cancer gene therapy and DNA vaccination.

PMID- 10943325
TI  - The mechanism of action of anti-inflammatory drugs.

PMID- 10943326
TI  - Human group-V phospholipase-A2 expression in Pichia pastoris and its role in
      eicosanoid generation.

PMID- 10943327
TI  - Fatty-acid substrate interactions with cyclo-oxygenases.

PMID- 10943329
TI  - Leukotriene-A4 hydrolase: probing the active sites and catalytic mechanisms by
      site-directed mutagenesis.

PMID- 10943328
TI  - Structure, function and inhibition of cyclo-oxygenases.

PMID- 10943330
TI  - The regulation of cyclooxygenase-1 and -2 in knockout cells and cyclooxygenase
      and fever in knockout mice.

PMID- 10943331
TI  - Leukotriene-B4 receptor and signal transduction.

PMID- 10943332
TI  - Lipoxins, aspirin-triggered 15-epi-lipoxin stable analogs and their receptors in
      anti-inflammation: a window for therapeutic opportunity.
AB  - LXs and 15-epimer LXs are generated during cell-cell interactions that occur
      during multicellular host response to inflammation, tissue injury or host
      defense. Results indicate that they are present in vivo during human illness and
      carry predominantly counter-regulatory biological actions opposing the action of
      well-characterized mediators of inflammation that appear to lead to resolution of
      the inflammatory response or promotion of repair and wound healing. The first
      selective receptor of LXA4 was identified by direct ligand binding and was cloned
      and characterized. Its signaling involves a novel polyisoprenyl-phosphate pathway
      that directly regulates PLD (Levy et al. 1999a). LX- and 15-epimer-LX-stable
      analogs that resist metabolic inactivation were designed, synthesized and shown
      to be potent LX mimetics and novel topically active anti-inflammatory agents in
      animal models. These new investigational tools enable structure-function studies
      of LX signal transduction, further elucidation of the role of LX and 15-epimer LX
      in host responses and exploitation of their potent bioactions in the design of
      novel pharmacologic agents.

PMID- 10943333
TI  - Lipoxin-stable analogs: potential therapeutic downregulators of intestinal
      inflammation.

PMID- 10943334
TI  - The role of eicosanoids in tumor growth and metastasis.

PMID- 10943335
TI  - [A little bit of history and truth in science and Venezuelan microbiology].

PMID- 10943336
TI  - The sophisticated survival strategies of the pathogen Listeria monocytogenes.
AB  - The function of the ActA protein of Listeria monocytogenes has been partially
      elucidated. These results illustrate the sophistication with which intracellular
      pathogens like Listeria use the host cell to their advantage, and have provided
      new insights into some of the molecular mechanisms of complex cell functions such
      as actin-promoted cell motility. The clarification of these processes is of
      fundamental importance not only for understanding elementary processes such as
      development and growth, but also for the treatment of both diseases caused by
      cytopathogenic bacteria such as Listeria and pathophysiological processes arising
      from disorders in cell motility and cell adhesion.

PMID- 10943337
TI  - Structure and properties of the outer membranes of Brucella abortus and Brucella
      melitensis.
AB  - The brucellae are Gram-negative bacteria characteristically able to multiply
      facultatively within phagocytic cells and which cause a zoonosis of world-wide
      importance. This article reviews the structure and topology of the main
      components (lipopolysaccharide, native hapten polysaccharide, free lipids and
      proteins) of the outer membranes of Brucella abortus and B. melitensis, as well
      as some distinctive properties (permeability and interactions with cationic
      peptides) of these membranes. On these data, an outer membrane model is proposed
      in which, as compared to other Gram-negatives, there is a stronger hydrophobic
      anchorage for the lipopolysaccharide, free lipids, porin proteins and
      lipoproteins, and a reduced surface density of anionic groups, which could be
      partially or totally neutralized by ornithine lipids. This model accounts for the
      permeability of Brucella to hydrophobic permeants and for its resistance to the
      bactericidal oxygen-independent systems of phagocytes.

PMID- 10943338
TI  - Cosmopolitan distribution of the large composite microbial mat spirochete,
      Spirosymplokos deltaeiberi.
AB  - Inocula from organic-rich black muds immediately underlying intertidal laminated
      microbial mats dominated by Microcoleus chthonoplastes yielded large, variable
      diameter spirochetes. These unusual spirochetes, previously reported only from
      the Alfacs Peninsula at the delta of the Ebro river in northeast Spain, contain
      striking arrays of cytoplasmic granules packed into their protoplasmic cylinders.
      On several occasions, both in summer and winter, the huge spirochetes were
      recognized in samples from mats growing in the Sippewissett salt marsh at Woods
      Hole Massachusetts. They were also seen in similar samples from microbial mats at
      North Pond, Laguna Figueroa, Baja California Norte, Mexico. The identity of these
      spirochetes was confirmed by electron microscopy: number and disposition of
      flagella, composite structure, measurements of their distinctive cytoplasmic
      granules. The granules, larger, more conspicuous and present in addition to
      ribosomes, are hypothesized to contain ATPases. As culture conditions worsen,
      these spirochetes retract into membrane-bounded round bodies in which they form
      refractile inclusions. From morphology and behavior we conclude the North
      American spirochetes from both Atlantic and Pacific intertidal microbial mats are
      indistinguishable from those at the delta of the Ebro river. We conclude a
      cosmopolitan distribution for Spirosymplokos deltaeiberi.

PMID- 10943339
TI  - Cloning, characterization and chromosomal localization of a repeated sequence in
      Crypthecodinium cohnii, a marine dinoflagellate.
AB  - Genomic DNA of Crypthecodinium cohnii has been extracted in the presence of
      cetylmethylammonium bromide and hydrolysed by 13 restriction enzymes. No typical
      ladder-like pattern or isolated band of satellite sequences were found with any
      of these enzymes. A "mini" genomic DNA library had been made and screened by
      reverse hybridization to isolate highly repeated sequences. Seven such DNA
      fragments were sequenced. The copy number of one of them (Cc18), 226 bp long, was
      estimated at around 25,000, representing 0.06% of the total genome. Cc18 was
      found to be included in a higher fragment of 3.0 kb by Southern blot analysis
      after cleavage by PstI. This higher molecular weight fragment could be composed
      either of tandemly repeated Cc18 sequences, or by only one or a very low copy
      number of Cc18. In this latter case, these fragments, also repeated 25,000 times
      would represent 1 to 2% of the total genome. Genomic localization of Cc18 by in
      situ hybridization on squashed C. cohnii cells showed that it was widely
      distributed on the different chromosomes. All the chromosomes observed displayed
      Cc18 labeling, which appeared homogeneously distributed. The ability of Cc18 to
      be a specific molecular marker to distinguish sibling C. cohnii species is
      discussed.

PMID- 10943340
TI  - Numerical taxonomy of heavy metal-tolerant nonhalophilic bacteria isolated from
      hypersaline environments.
AB  - A total of 232 metal-tolerant bacterial strains were isolated from water and
      sediment samples collected in different hypersaline environments located in
      Cadiz, Huelva and Moron de la Frontera (Spain). They were isolated on a medium
      containing mercury, chromium, cadmium, copper or zinc. These halotolerant
      isolates were analyzed by numerical taxonomy techniques by using the simple
      matching (SSM) and Jaccard (SJ) coefficients; clustering was achieved using the
      unweighted pair group method with averages (UPGMA) algorithm. At the 81% and 83%
      similarity level, different numbers of phenons were obtained for Gram-negative
      and Gram-positive halotolerant microorganisms. Most of the 48 Gram-negative metal
      tolerant strains studied were grouped into nine phenons, representing the genera
      Pseudoalteromonas, Alteromonas, Xanthomonas, Pseudomonas, Alcaligenes and
      Enterobacteria. The 72 Gram-positive metal-tolerant strains grouped into eight
      phenons, with only 15 strains left unassigned. Most of the isolates were assigned
      to the genus Bacillus (seven phenons), and one phenon comprised microorganisms
      with phenotypic characteristics similar to those of the genus Celullomonas.

PMID- 10943341
TI  - Efficient phagocytosis of Klebsiella pneumoniae strains that poorly bind to human
      polymorphonuclear leukocytes.
AB  - The phagocytosis process of unencapsulated MIAT-negative strains that, although
      binding very poorly to human polymorphonuclear leukocytes (PMN) at 4 degrees C,
      are efficiently killed by these cells at 37 degrees C, was studied. At 37 degrees
      C the number of bacteria bound to the PMN external surface was similar to that
      observed at 4 degrees C (about 100 bacteria/100 PMN after 60 min); on the
      contrary the number of internalized bacteria was much higher (from 500
      bacteria/100 PMN after 60 min). Interactions between phagocytosis-sensitive
      Klebsiella pneumoniae strains (PSK) and PMN were then compared with those of two
      isogenic Escherichia coli strains with and without type 1 fimbriae. Whereas PSK
      strain binding to blocked PMN was very slow and became significant only after 5-6
      h, that of phagocytosis-sensitive fimbriated E. coli was rapid and efficient.
      Phagocytosis-resistant, non fimbriated E. coli strain bound with an efficiency
      that, within the first 60 min, was not very different from that of the PSK
      strains. However, longer incubations led to increases in PSK binding, whereas
      unfimbriated E. coli remained constant. PSK and fimbriated E. coli strains were
      efficiently internalized and killed, whereas the unfimbriated E. coli strain was
      not. It is suggested that PMN can phagocytize unopsonized bacteria through two
      different mechanisms. By one mechanism, observed with the fimbriated E. coli
      strain, PMN bind many more bacteria than those they can internalize. By the
      other, observed with PSK strains, PMN bind only the bacteria they can immediately
      internalize.

PMID- 10943342
TI  - Multicolonization of human nasopharynx due to Neisseria spp.
AB  - The colonization due to Neisseria spp. in the nasopharynx of forty healthy adults
      was studied by using a selective medium that allows the differentiation of
      Neisseria species and inhibits the rest of pharyngeal microbiota. The medium
      detected a variety of colonial morphology types and some metabolic
      characteristics of the isolates. We demonstrated the multicolonization by several
      Neisseria spp. in the same individual, and we isolated several strains of the
      same species, after analysis by pulsed-field gel electrophoresis (PFGE) patterns
      obtained from the different colonial types previously identified as the same
      species. The forty adults studied were colonized by 112 forms of Neisseria spp.,
      and twelve colonization patterns were obtained: one species (45%), two (45%),
      three (7.5%) and four (2.5%). N. perflava-N. sicca, either alone or in
      combination with other species was the most frequent isolate (92.5%). The
      analysis of PFGE patterns obtained from different colonial types revealed the
      multicolonization by several strains of the same species in some individuals.
      This fact was found in N. perflava-N. sicca (50%) and N. mucosa (2.5%).

PMID- 10943343
TI  - Microbe Hunters revisited.

PMID- 10943345
TI  - Learning science and doing science. How closely are they related?

PMID- 10943344
TI  - Lourens G. M. Baas Becking (1895-1963). Inspirator for many (micro)biologists.

PMID- 10943346
TI  - [Science in Colombia: from utopia to reality].

PMID- 10943347
TI  - Candida albicans: genetics, dimorphism and pathogenicity.
AB  - Candida albicans is a dimorphic fungus that causes severe opportunistic
      infections in humans. Recent advances in molecular biology techniques applied to
      this organism (transformation systems, gene disruption strategies, new reporter
      systems, regulatable promoters) allow a better knowledge of both the molecular
      basis of dimorphism and the role of specific genes in Candida morphogenesis.
      These same molecular approaches together with the development of appropriate
      experimental animal models to analyze the virulence of particular mutants, may
      help to understand the molecular basis of Candida virulence.

PMID- 10943348
TI  - The cell wall structure: developments in diagnosis and treatment of candidiasis.
AB  - Candidiasis are among the fungal infections the most difficult to diagnose and
      treat. Research focused on specific fungal components which are absent in the
      host, such as the cell wall has lead to a better understanding of Candida
      albicans pathogenicity and clinical impact. The cell wall is responsible for
      antigenic expression and primary interaction with the host. It is composed mainly
      of beta-glucans, chitin and mannoproteins, which account for the rigidity of the
      wall and for the fungal morphology. Of these components, mannoproteins might
      carry a "morphogenetic code" which might modulate the molecular architecture of
      the cell wall. The features of specific cell wall proteins as part of building
      blocks to form this structure is revised, and the usefulness of monoclonal
      antibodies obtained against cell wall components to study those processes,
      together with their clinical applicability, is discussed.

PMID- 10943349
TI  - Candida adherence phenomena, from commensalism to pathogenicity.
AB  - Molecules present in the most external layers of Candida cells are essential for
      the adherence to host surfaces, playing a pivotal role in the pathophysiology of
      candidiasis. Receptors for fibrinogen, fibronectin and other components of the
      extracellular matrix have been described in Candida surfaces. Their expression
      may be influenced by particular host conditions, and these changes may be
      important in the transition from commensalism to pathogenicity. Surface proteins
      are also essential in the interactions of the fungal cell with the various
      constitutive, inducible defense host mechanisms that act during candidiasis.

PMID- 10943350
TI  - Yarrowia lipolytica: a model organism for protein secretion studies.
AB  - This paper reviews the advantages of the yeast Yarrowia lipolytica as a tool in
      the study of protein secretion. Work has been focused on the early steps leading
      the polypeptide, from the cytoplasmic ribosomes where it is synthesized, to the
      lumen of the endoplasmic reticulum. Using a thermosensitive allele of the 7SL
      RNA, the first in vivo evidence for a co-translational translocation was shown.
      Genetic screens allowed the identification of several new components of the
      translocation apparatus: Sls1p, an ER lumenal component involved in both
      translocation and lumenal transit; Tsr1p, involved in SRP-ribosome targeting;
      Tsr3p. Major translocation partners were also identified by reverse genetics
      (Sec61p, Sec62p, Kar2p, Srp54p, Sec65p).

PMID- 10943351
TI  - Non-conventional yeasts as hosts for heterologous protein production.
AB  - Yeasts are an attractive group of lower eukaryotic microorganisms, some of which
      are used in several industrial processes that include brewing, baking and the
      production of a variety of biochemical compounds. More recently, yeasts have been
      developed as host organisms for the production of foreign (heterologous)
      proteins. Saccharomyces cerevisiae has usually been the yeast of choice, but an
      increasing number of alternative non-Saccharomyces yeasts has now become
      accessible for modern molecular genetics techniques. Some of them exhibit certain
      favourable traits such as high-level secretion or very strong and tightly
      regulated promoters, offering significant advantages over traditional bakers'
      yeast. In the present work, the current status of Kluyveromyces lactis, Yarrowia
      lipolytica, Hansenula polymorpha and Pichia pastoris (the best-known alternative
      yeast systems) is reviewed. The advantages and limitations of these systems are
      discussed in relation to S. cerevisiae.

PMID- 10943352
TI  - The role of non-Saccharomyces yeasts in industrial winemaking.
AB  - The fermentation of grape juice into wine is a complex microbiological process,
      in which yeasts play a central role. Traditionally, identification and
      characterization of yeast species have been based on morphological and
      physiological characteristics. However, the application of molecular biology
      techniques represents an alternative to the traditional methods of yeast
      identification and are becoming an important tool in solving industrial problems.
      Although Saccharomyces cerevisiae is responsible for the alcoholic fermentation,
      the presence of non-Saccharomyces species could be important since they produce
      secondary metabolites, which can contribute to the final taste and flavor of
      wines.

PMID- 10943353
TI  - The fungus Ustilago maydis, from the aztec cuisine to the research laboratory.
AB  - Ustilago maydis is a plant pathogen fungus responsible for corn smut. It has a
      complex life cycle. In its saprophitic stage, it grows as haploid yeast cells,
      while in the invasive stage it grows as a mycelium formed by diploid cells. Thus,
      a correlation exists between genetic ploidy, pathogenicity and morphogenesis.
      Dimorphism can be modulated in vitro by changing environmental parameters such as
      pH. Studies with auxotrophic mutants have shown that polyamines play a central
      role in regulating dimorphism. Molecular biology approaches are being employed
      for the analysis of fundamental aspects of the biology of this fungus, such as
      mating type regulation, dimorphism or cell wall biogenesis.

PMID- 10943354
TI  - Lamarck and the prehistory of ecology.

PMID- 10943355
TI  - Meeting the biospheres: on the translations of Vernadsky's work.

PMID- 10943356
TI  - [Society facing the impact of techno-scientific progress].

PMID- 10943357
TI  - [Science and scientific production in Latin America. The Latindex project].

PMID- 10943358
TI  - Prions: an evolutionary perspective.
AB  - Studies in both prion-due diseases in mammals and some non-Mendelian hereditary
      processes in yeasts have demonstrated that certain proteins are able to transmit
      structural information and self-replication. This induces the corresponding
      conformational changes in other proteins with identical or similar sequences.
      This ability of proteins may have been very useful during prebiotic chemical
      evolution, prior to the establishment of the genetic code. During this stage,
      proteins (proteinoids) must have molded and selected their structural folding
      units through direct interaction with the environment. The proteinoids that
      acquired the ability to propagate their conformations (which we refer to as
      conformons) would have acted as reservoirs and transmitters of a given structural
      information and hence could have acted as selectors for conformational changes.
      Despite the great advantage that arose from the establishment of the genetic
      code, the ability to propagate conformational changes did not necessarily
      disappear. Depending on the degree of involvement of this capacity in biological
      evolution, we propose two not mutually exclusive hypotheses: (i) extant prions
      could be an atavism of ancestral conformons, which would have co-evolved with
      cells, and (ii) the evolution of conformons would have produced cellular
      proteins, able to transmit structural information, and, in some cases,
      participating in certain processes of regulation and epigenesis. Therefore,
      prions could also be seen as conformons of a conventional infectious agent (or
      one that co-evolved with it independently) that, after a longer or shorter
      adaptive period, would have interacted with conformons from the host cells.

PMID- 10943359
TI  - Human enteric viruses in the water environment: a minireview.
AB  - Water virology started around half a century ago, with scientists attempting to
      detect poliovirus in water samples. Since that time, other enteric viruses
      responsible for gastroenteritis and hepatitis, among a great variety of virus
      strains, have replaced enteroviruses as the main target for detection in the
      water environment. Technical molecular developments, polymerase-chain reaction
      (PCR) amplification being the method of choice, enable the detection of
      fastidious health-significant viruses. However, shortcomings of molecular
      procedures include their potential incompatibility with concentration methods,
      indispensable to reduce the water sample volume to assay for viruses, the
      inability to discern between infectious and non infectious material. On the other
      hand, these procedures are restrained to sophisticated laboratories and detection
      of alternative indicator organisms has been proposed. Bacterial indicators fail
      to give a reliable clue of the virological quality of water. Selected
      bacteriophage groups appear as a better choice for their use as virus indicators.

PMID- 10943360
TI  - Molecular mechanisms of Salmonella invasion: the type III secretion system of the
      pathogenicity island 1.
AB  - Salmonella spp. are facultative intracellular pathogens which are able to enter
      into non-phagocytic cells as an essential step in their pathogenic life cycle.
      The majority of the molecular determinants involved in this entry process are
      encoded in a pathogenicity island located at the centisome 63 of the bacterial
      chromosome, and belong to a specialized protein secretion system termed "type
      III" or "contact-dependent". This secretion system is used by Salmonella spp. and
      several other bacterial pathogens to translocate bacterial effector proteins into
      the eukaryotic cell. Thus, a bidirectional biochemical cross-talk with the host
      cell is initiated, which leads to several responses such as membrane ruffling,
      bacterial internalization and the activation of various transcription factors.

PMID- 10943361
TI  - Yeast communities associated with sugarcane in Campos, Rio de Janeiro, Brazil.
AB  - Yeast communities associated with sugarcane leaves, stems and rhizosphere during
      different phases of plant development were studied near Campos, in Rio de
      Janeiro, Brazil. Atmospheric temperature, soil granulometry and pH, and sugar
      cane juice degree Brix and pH were determined. Yeast communities associated with
      sugarcane were obtained after cellular extraction by shaking, blending and
      shaking plus sonication, and cultured on Yeast Nitrogen Base Agar plus glucose
      (0.5%) and Yeast Extract-Malt Extract Agar. No significant differences in yeast
      counts were found among the cellular extraction treatments and culture media. 230
      yeast cultures were identified according to standard methods, and distinct yeast
      communities were found for each substrate studied. The prevalent species isolated
      from sugarcane were Cryptococcus laurentii, Cryptococcus albidus, Rhodotorula
      mucilaginosa and Debaryomyces hansenii.

PMID- 10943362
TI  - Candida albicans fibrinogen binding mannoprotein: expression in clinical strains
      and immunogenicity in patients with candidiasis.
AB  - A 58 kDa cell wall-associated fibrinogen binding mannoprotein (mp58), previously
      characterized by our group in a Candida albicans laboratory strain (ATCC 26555),
      was found to be also present in the cell wall of clinical isolates of this
      fungus. Most strains examined appear to have functional mp58 species, as detected
      by their ability to bind fibrinogen. Western immunoblot analysis, with a
      monovalent polyclonal antibody generated against the mp58 species from strain
      ATCC 26555, revealed differences in recognition patterns depending on the strain
      tested and the culture conditions used. Serum samples from normal and Candida
      infected individuals were examined for the presence of antibodies against mp58 by
      Western immunoblotting. None of the sera from control individuals and patients
      suffering from superficial candidiasis contained antibodies against mp58.
      However, positive reactivity with this antigen and other cell wall constituents
      was detected for all sera from patients with confirmed systemic candidiasis.
      Together, these results suggest that mp58 could play an active role during
      infection and may be useful as a specific antigenic marker for candidiasis.

PMID- 10943363
TI  - A protocol for PCR in situ hybridization of hyphomycetes.
AB  - A protocol for application of Polymerase Chain Reaction (PCR) in situ
      hybridization for the detection of hyphomycetes is presented. The experiments are
      exemplary carried out with strains of the genera Penicillium and Cladosporium.
      The small ribosomal subunit is amplified in situ by PCR using fungal specific
      primers. The amplicon is used as target region for a fluorescein-marked probe.
      The permeability of the fungal cell wall for the primers and the probe can be
      successfully achieved by enzymatic treatment with beta-glucanase. The protocol
      can be used as a basis for further development of in situ hybridization with
      taxon specific probes.

PMID- 10943364
TI  - Colimetry of marine waters off Fortaleza (Ceara State, Brazil) and detection of
      enteropathogenic Escherichia coli strains.
AB  - Bacteriological analyses of seawater from three main beaches in Fortaleza, Brazil
      were performed during 1997. Thirty-six samples per beach were collected for a
      total of 108 samples. For Meireles Beach, 44% of the samples had MPN total
      coliforms values of at least 1100 or over 2400/100 ml, followed by Formosa and
      Diarios beaches showing lower counts. For fecal coliforms the highest numbers
      were demonstrated for Formosa, followed by Meireles and Diarios beaches in this
      descending order: 13.0%, 11.1% and 8.3%, respectively. Escherichia coli strains
      were identified in 76.8% of the 108 samples. Among 295 strains of E. coli, 21
      belonged to serogroups O25, O26, O91, O112, O119, O158 and O164. Strains from
      serogroup O26 were tested using PCR, ELISA and Vero cells to detect Verotoxins
      VT1 and VT2 and all strains were negative. No LT and ST, as determined by ELISA
      and suckling mice assays, were detected among the 295 strains. All strains of E.
      coli were sensitive to ampicillin, cephalothin, gentamicin, tetracycline,
      sulfametox-trimethoprim, chloramphenicol and ciprofloxacin. Although the E. coli
      strains were not toxigenic, their presence in high numbers could be of public
      health significance.

PMID- 10943365
TI  - Partial characterization and photolabeling of a Rhizobium meliloti polysaccharide
      methyltransferase with S-adenosylmethionine.
AB  - S-Adenosylmethionine (SAM) has been used to directly cross-link a polysaccharide
      specific methyltransferase isolated from Rhizobium meliloti HA. This peculiar
      enzyme transfers a methyl group to the 2-O-galacturonosyl residue of a
      teichuronic type polysaccharide and was very unstable. The apparent Km for SAM
      was 0.46 mM. The Hill coefficient, n, was 1. The enzyme had an optimum pH of 8.2
      and requires Mn2+ at concentration of 2 mM. The enzyme was inactivated by saline
      concentrations of 120 mM or greater and was eluted from Superose columns with an
      apparent molecular weight of 28 kDa. The isoelectric point was close to 7.0. To
      elucidate the relationship between chemical structure and catalytic function,
      (3H)SAM was cross-linked to the enzyme and the enzymatic activity was assayed in
      presence and in absence of commercial substrate analogs. Cross-linking was
      performed by direct irradiation of enzyme and (3H)SAM. The uptake of
      radioactivity was linear up to about 20 min and then reached a plateau. This
      irreversible junction is specific, as shown by a number of different criteria.
      Several competitive inhibitors were able to affect this photoactivated cross
      linkage. As the concentration of inhibitors increased, both, the level of
      photolabeling and enzyme activity always decreased. The SAM-enzyme adduct was
      shown to be a single protein band by SDS polyacrylamide gel electrophoresis.

PMID- 10943366
TI  - Clair C. Patterson (1922-1995), discoverer of the age of the Earth.

PMID- 10943367
TI  - One hundred years of centrioles: the Henneguy-Lenhossek theory, meeting report.

PMID- 10943368
TI  - Foreign languages in tertiary education. An assessment.

PMID- 10943369
TI  - Year's comments for 1998.

PMID- 10943370
TI  - Ten years of CIBE symposia, 1989-1998.

PMID- 10943371
TI  - The renaissance of microbiology.
AB  - Microbiology is finally occupying its true position as the pre-eminent field in
      life sciences. This is due to advances in molecular techniques that confirm the
      evolutionary significance of the biology of microbes. It is anticipated that the
      use of comparative genomics will provide information that will advance the
      understanding of mechanisms of pathogenesis and the importance of secondary
      metabolism in social microbiology. More emphasis on studies of microbial
      diversity will increase its value in both fundamental microbiology and its
      industrial applications.

PMID- 10943372
TI  - Induction of microbial secondary metabolism.
AB  - Precursors often stimulate production of secondary metabolites either by
      increasing the amount of a limiting precursor, by inducing a biosynthetic enzyme
      (synthase) or both. These are usually amino acids but other small molecules also
      function as inducers. The most well-known are the auto-inducers which include
      gamma-butyrolactones (butanolides) of the actinomycetes, N-acylhomoserine
      lactones of Gram-negative bacteria, oligopeptides of Gram-positive bacteria, and
      B-factor (3'-[1-butylphosphoryl] adenosine) of Amycolatopsis mediterranei. The
      actinomycete butanolides exert their effects via receptor proteins which normally
      repress chemical and morphological differentiation (secondary metabolism and
      differentiation into aerial mycelia and spores respectively) but, when complexed
      with the butanolide, can no longer function. Homoserine lactones of Gram-negative
      bacteria function at high cell density and are structurally related to the
      butanolides. They turn on plant and animal virulence, light emission, plasmid
      transfer, and production of pigments, cyanide and beta-lactam antibiotics. They
      are made by enzymes homologous to Lux1, excreted by the cell, enter other cells
      at high density, bind to a LuxR homologue, the complex then binding to DNA
      upstream of genes controlled by "quorum sensing" and turning on their expression.
      Quorum sensing also operates in the case of the peptide pheromones of the Gram
      positive bacteria. Here, secretion is accomplished by an ATP binding casette (ABC
      transporter), the secreted pheromone being recognized by a sensor component of a
      two-component signal transduction system. The pheromone often induces its own
      synthesis as well as those proteins involved in protein/peptide antibiotic
      (including bacteriocins and lantibiotics) production, virulence and genetic
      competence. The B-factor of A. mediterranei is an inducer of ansamycin
      (rifamycin) formation.

PMID- 10943373
TI  - Bacterial evolution and the cost of antibiotic resistance.
AB  - Bacteria clearly benefit from the possession of an antibiotic resistance gene
      when the corresponding antibiotic is present. But do resistant bacteria suffer a
      cost of resistance (i.e., a reduction in fitness) when the antibiotic is absent?
      If so, then one strategy to control the spread of resistance would be to suspend
      the use of a particular antibiotic until resistant genotypes declined to low
      frequency. Numerous studies have indeed shown that resistant genotypes are less
      fit than their sensitive counterparts in the absence of antibiotic, indicating a
      cost of resistance. But there is an important caveat: these studies have put
      resistance genes into naive bacteria, which have no evolutionary history of
      association with the resistance genes. An important question, therefore, is
      whether bacteria can overcome the cost of resistance by evolving adaptations that
      counteract the harmful side-effects of resistance genes. In fact, several
      experiments (in vitro and in vivo) show that the cost of antibiotic resistance
      can be substantially diminished, even eliminated, by evolutionary changes in
      bacteria over rather short periods of time. As a consequence, it becomes
      increasingly difficult to eliminate resistant genotypes simply by suspending the
      use of antibiotics.

PMID- 10943374
TI  - Evolution of the clusters of genes for beta-lactam antibiotics: a model for
      evolutive combinatorial assembly of new beta-lactams.
AB  - beta-Lactam antibiotics are produced by prokaryotic and eukaryotic organisms. The
      genes for beta-lactam biosynthesis are organized in clusters but the location of
      the different genes is not identical. Biosynthesis genes are clustered with genes
      for resistance (bla, pbp) and for the efflux of the antibiotic (cmcT) in
      prokaryotes. Comparison of proteins reveals much larger differences for primary
      metabolism enzymes than for beta-lactam biosynthesis enzymes in producing
      organisms. This suggests a horizontal transfer of the beta-lactam antibiotic
      biosynthesis genes.

PMID- 10943375
TI  - Evolution of bacterial resistance to antibiotics during the last three decades.
AB  - Bacterial resistance to antibiotics is often plasmid-mediated and the associated
      genes encoded by transposable elements. These elements play a central role in
      evolution by providing mechanisms for the generation of diversity and, in
      conjunction with DNA transfer systems, for the dissemination of resistances to
      other bacteria. At the University Hospital of Zaragoza, extensive efforts have
      been made to define both the dissemination and evolution of antibiotic resistance
      by studying the transferable R plasmids and transposable elements. Here we
      describe the research on bacterial resistance to antibiotics in which many
      authors listed in the references have participated. The aspects of bacterial
      resistance dealt with are: (i) transferable resistance mediated by R plasmids in
      Gram-negative bacteria, (ii) R plasmid-mediated resistance to apramycin and
      hygromycin in clinical strains, (iii) the transposon Tn1696 and the integron In4,
      (iv) expression of Escherichia coli resistance genes in Haemophilus influenzae,
      (v) aminoglycoside-modifying-enzymes in the genus Mycobacterium with no relation
      to resistance, and (vi) macrolide-resistance and new mechanisms developed by Gram
      positive bacteria.

PMID- 10943376
TI  - Crucial crises in biology: life in the deep biosphere.
AB  - The origin and evolution of life on Earth are the result of a series of crises
      that have taken place on the planet over about 4500 millions of years since it
      originated. Biopoiesis (origin of life), ecopoiesis (origin of ecosystems) and
      the first ecosystems (stromatolites and microbial mats), as well as
      eukaryopoiesis (origin of nucleated cells) are revised. The paper then focuses on
      the study of the deep biosphere, describing ecosystems never found before, which
      are independent of solar radiation and have changed previous assumptions about
      the requirements of life; even the concept of biosphere, as Vernadsky defined it,
      has increased its scope. Since the discovery, in 1987, of bacteria growing in the
      crevices of rocks at 500 m deep, in boreholes drilled near the Savanna River,
      Aiken, South Carolina, other bacteria have been found in the deep subsurface
      reaching depths of about 3 km (e.g., in the Columbia River Basalt Group, near
      Richland, Washington state), in an anaerobic, hot, high-pressure environment.
      Some kinds of microorganisms can thrive at such depths, living in many cases a
      geochemical existence, by using very specialized metabolisms, which depend on the
      local environments. The existence of organisms independent from photosynthetic
      production is the most outstanding, novel feature of the deep biosphere. Living
      beings might not need other energy and chemical sources than those which occur in
      the development of all planetary bodies. Life, therefore, could even be an
      ineluctable outcome of planetary evolution and, as a corollary, a natural
      continuation of the usual development of physical phenomena in the universe.

PMID- 10943377
TI  - Selection of very small differences in bacterial evolution.
AB  - As the Science of Biology is constantly changing due to new discoveries and
      advanced techniques it is essential that a systematic study of the environmental
      causes of natural selection on microorganisms be conducted. Very small phenotypic
      differences among individuals within bacterial populations arise as a result of
      spontaneous genetic variation, but the evolutionary importance of these small
      changes is frequently considered to be non-significant. Recent in vitro
      experiments indicate that efficient selection of these very small differences may
      take place in environmental compartments where a particular intensity of the
      selective agent is exerted. Model studies based on competition between bacterial
      populations only differing in one or two amino acid changes of a detoxifying
      antibiotic enzyme (e.g. beta-lactamase) have shown that at a narrow range of
      antibiotic concentrations the variant population is strongly selected over the
      original type, despite the extremely low phenotypic differences in antibiotic
      susceptibility. These selective concentrations are expected to occur in precise
      environmental compartments (selective compartments). Due to the high frequency of
      structured habitats in natural environments, the intensity of selective agents is
      commonly exerted along certain gradients. Each one of the points forming these
      gradients (or intersection among gradients) may have a particular selective
      ability for a specific genetic variant. Considering the environment as a
      composition of an extremely high number of specific selective compartments may
      help to understand the existence of high levels of genetic variability in natural
      bacterial populations. This may be one of the clues towards the unraveling of
      bacterial evolution.

PMID- 10943378
TI  - The evolution of function: a new method to assess the phylogenetic value of
      ribosomal sensitivity to antibiotics.
AB  - Thirty-five archaeal, bacterial and eukaryotic translational systems have been
      proved against forty different protein synthesis inhibitors with diverse domain
      and functional specificities. The inhibition curves generated in every ribosome
      antibiotic combination had previously shown interesting similarities among
      organisms belonging to the same phylogenetic group. This opened the possibility
      of using such functional information for developing evolutionary studies. A new
      mathematical method based on the main data components analysis has been developed
      to extract most of the information contained in the inhibition curves. The
      phenograms obtained closely resemble those generated by the small ribosomal
      subunit rRNA sequence comparison and such functional clustering is also congruent
      when a particular subset of organisms and/or antibiotics is used. These results
      prove the phylogenetic value of our functional analysis and suggest that the
      ribosome represents an interesting intersection between genotypic and phenotypic
      (functional) information stored in organisms.

PMID- 10943379
TI  - Control mechanisms of bacteriophage phi 29 DNA expression.
AB  - The phage phi 29 regulatory protein p4 activates the late promoter A3 by
      stabilizing the binding of Bacillus subtilis RNA polymerase (RNAP) as a closed
      complex. Interaction between the two proteins occurs through amino acid Arg120 in
      protein p4 and the C-terminal domain of the RNAP alpha subunit (alpha-CTD). In
      addition to its role as activator of the late transcription, protein p4 represses
      early transcription from the A2b and A2c promoters, that are divergently
      transcribed. Binding of p4 to its recognition site at the A3 promoter displaces
      the RNAP from promoter A2b, both by steric hindrance and by the curvature induced
      upon p4 binding. At the A2c promoter, the RNAP cooperates with p4 binding in such
      a way that promoter clearance is prevented. Interestingly, amino acid Arg120 in
      p4 and the alpha-CTD in B. subtilis RNAP are involved in the interactions that
      lead to transcription repression at promoter A2c. To investigate how this
      interaction leads to activation at PA3 and to repression at PA2c, mutant
      promoters were constructed. In the absence of a -35 consensus box for sigma A
      RNAP activation was observed, while in its presence repression occurred. The
      results support the idea that overstabilization of RNAP at the promoter over a
      threshold level leads to repression.

PMID- 10943380
TI  - The foot-and-mouth disease RNA virus as a model in experimental phylogenetics.
AB  - Phylogenetic reconstruction methods are subject to two types of limitations: our
      knowledge about the true history of organisms and the gross simplification
      implied in the numerical simulation models of the relationships between them. In
      such a situation, experimental phylogenetics provides a way to assess the
      accuracy of the phylogenetic reconstruction methods. Nonetheless, this capacity
      is only feasible for organisms in which replication and mutation rates are high
      enough to provide valuable data. On the other hand, experimental phylogenetics
      also provides insights on the main evolutionary processes acting on viral
      variability under different population dynamics. Our study with the foot-and
      mouth disease virus (FMDV) strongly suggests that the phylogenetic reconstruction
      methods can infer erroneous phylogenies due to nucleotide convergences between
      isolates belonging to different experimental lineages. We also point out that the
      diverse evolutionary mechanisms acting in different experimental dynamics
      generate alterations and change the frequencies of genetic variants, which can
      lead to the misinterpretation of the real evolutionary history.

PMID- 10943381
TI  - Morphogenesis by symbiogenesis.
AB  - Here we review cases where initiation of morphogenesis, including the
      differentiation of specialized cells and tissues, has clearly evolved due to
      cyclical symbiont integration. For reasons of space, our examples are drawn
      chiefly from the plant, fungal and bacterial kingdoms. Partners live in symbioses
      and show unique morphological specializations that result when they directly and
      cyclically interact. We include here brief citations to relevant literature where
      plant, bacterial or fungal partners alternate independent with entirely
      integrated living. The independent, or at least physically unassociated stages,
      are correlated with the appearance of distinctive morphologies that can be traced
      to the simultaneous presence and strong interaction of the plant with individuals
      that represent different taxa.

PMID- 10943382
TI  - Mitochondrial DNA: a tool for populational genetics studies.
AB  - Mitochondria are cellular organelles that have the function of the oxidative
      phosphorilation and the formation of ATP. In humans, the mtDNA is a double
      stranded, circular, covalent closed molecule of 16.5 kb. The mtDNA is inherited
      as a haploid from the mother and heteroplasmy has been found rarely. From a
      populational perspective, it could be considered as a system of small, sexually
      isolated demes, or clonal lineages, with an evolutionary rate 5 to 10 times
      faster than the nuclear genome. All these characteristics make this molecule
      ideal for evolutionary studies. We present two applications of this molecule in
      genetical studies. One of these is referred to the Balearic Islands populations,
      Majorca, Minorca, Ibiza, and Chuetas. The other example is the populational
      dynamics of the different mitochondrial haplotypes in Drosophila subobscura. We
      also discuss the importance of nuclear markers to complete these studies as well
      as the study of the Y chromosome to compensate the bias produced by the study of
      only the mtDNA.

PMID- 10943383
TI  - What is microbiology gaining from genomics?

PMID- 10943384
TI  - Comparative biochemistry of CO2 fixation and the evolution of autotrophy.
AB  - Carbon dioxide fixation is a polyphyletic trait that has evolved in widely
      separated prokaryotic branches. The three principal CO2-assimilation pathways are
      (i) the reductive pentose-phosphate cycle, i.e. the Calvin-Benson cycle; (ii) the
      reductive citric acid (or Arnon) cycle; and (iii) the net synthesis of acetyl-CoA
      from CO/CO2, or Wood pathway. Sequence analysis and the comparative biochemistry
      of these routes suggest that all of them were shaped to a considerable extent by
      the evolutionary recruitment of enzymes. Molecular phylogenetic trees show that
      the Calvin-Benson cycle was a relatively late development in the (eu)bacterial
      branch, suggesting that some form(s) of carbon assimilation may have been
      operative before chlorophyll-based photosynthesis. On the other hand, the ample
      phylogenetic distribution of both the Arnon and the Wood pathways does not allow
      us to infer which one of them is older. However, different lines of evidence,
      including experimental reports on the NiS/FeS-mediated C-C bond formation from CO
      and CH3SH are used here to argue that the first CO2-fixation route may have been
      a semi-enzymatic Wood-like pathway.

PMID- 10943385
TI  - Accelerated evolution in bacterial endosymbionts of aphids.
AB  - When compared with free living bacteria, it is proposed that there are at least
      two endosymbiotic processes in aphids based on the A + T content as well as the
      increased evolutionary rate of the beta-subunit of the F-ATPase complex in
      different endosymbiotic bacteria. The first well established process corresponds
      to the integration of Buchnera aphidicola more than 150 million years ago. The
      other is postulated to correspond to new endosymbiotic processes in which the
      bacteria involved contain less A + T and show a lower increase of evolutionary
      rates when compared with B. aphidicola. It is proposed, therefore, that
      endosymbioses are active processes in aphid evolution.

PMID- 10943386
TI  - Adaptive responses in Chlamydomonas reinhardtii.
AB  - The photosynthetic single cellular alga Chlamydomonas reinhardtii has been used
      as a model organism to examine in detail the physiological, biochemical and
      molecular processes of photosynthesis, flagella synthesis and movement, mineral
      stress, interactions between nucleus, chloroplasts and mitochondria and other
      processes. In this review we summarize part of the current knowledge on adaptive
      responses in C. reinhardtii when it is exposed to oxidative stress and to changes
      in light intensity, concentration of minerals, herbicides and metals. The
      individual responses are linked in order to understand the response of the cell,
      which is continuously subjected to fluctuations, as a whole.

PMID- 10943388
TI  - Construction of plasmid vectors bearing a NotI-expression cassette based on the
      lac promoter.
AB  - We have constructed two plasmid vectors for cloning and expression of DNA
      fragments controlled by the lac promoter as a NotI-expression cassette. Whereas
      plasmid pSJ33 allows mobilization of the expression cassette into a wide variety
      of Gram-negative bacteria by RP4-mediated conjugation, the low-copy-number
      plasmid pSJP18Not facilitates cloning and expression in Escherichia coli when
      high gene dosage may be detrimental. In addition to their suitable cloning
      features (e.g. multiple cloning site, lacZ alpha fragment, compatible with ColE1
      derived vectors), these plasmids are particularly useful as auxiliary vectors for
      cloning of the expression cassettes at the NotI site of mini-transposon elements
      [1, 2] and their eventual stable insertion into the host chromosome.

PMID- 10943387
TI  - Construction of a new Streptococcus pneumoniae-Escherichia coli shuttle vector
      based on the replicon of an indigenous pneumococcal cryptic plasmid.
AB  - The nucleotide sequence of a cryptic plasmid (pRMG1) isolated from a type 1
      Streptococcus pneumoniae has been determined and two recombinant plasmids, pRMGE1
      and pRMGE2, bearing the pRMG1 replicon have been constructed. pRMGE2 is a shuttle
      vector for Escherichia coli and S. pneumoniae. The important characteristics of
      this cloning vector are: a size of 5.5 kb including a 1.4 kb fragment of pRMG1
      (containing a double-stranded replication origin and an open reading frame
      encoding a putative replication initiation protein), a multicloning site, two
      antibiotic resistance markers for selection of plasmid containing cells, and blue
      white colony screening in E. coli for identification of insert-containing
      plasmids.

PMID- 10943389
TI  - Inactive and temperature-sensitive folding mutants of aldehyde dehydrogenase of
      Escherichia coli.
AB  - Aldehyde dehydrogenase, encoded by the aldA gene in Escherichia coli, is inactive
      in nitrosoguanidine induced mutant strain ECL40 and temperature-sensitive in
      spontaneous mutant strain JA104. Both mutants were proven, by complementation
      experiments, to have a functional aldA regulator and promoter. In spite of no
      immunodetection of the aldA product, its specific transcript was present in the
      mutant extracts. It was subsequently proven that the immunodetection of aldehyde
      dehydrogenase in these mutants required denaturation, revealing that cells
      lacking the enzyme activity had the inactive protein in their extracts. Thus, the
      mutations seemed to affect the protein conformation. The temperature-sensitive
      aldehyde dehydrogenase did not show, neither in vivo nor in vitro, a different
      thermal stability compared to the wild type enzyme. In this temperature-sensitive
      strain, the recovery of active aldehyde dehydrogenase, in the presence of
      rifampicin but not of chloramphenicol, when cells grown at 37 degrees C were
      shifted to 30 degrees C indicated that this mutation affected the folding process
      of the protein at the restrictive temperature. Sequencing of the two mutant aldA
      corresponding genes determined a single amino acid change of Pro to Leu at
      position 182 for strain ECL40, and of Val to Met at position 145 for strain
      JA104. These mutations were thought to possibly promote changes in the local
      flexibility in the first case, and to perturb the packing of residues by steric
      hindrance in the second case.

PMID- 10943390
TI  - Snow algae of the Sierra Nevada, Spain, and High Atlas mountains of Morocco.
AB  - Snow algae (Chlorophyta) are reported from the Sierra Nevada mountains in
      southern Spain and the High Atlas mountains of Morocco. Populations of the snow
      algae Chlamydomonas sp., coloring the snow orange-red, were collected from Pico
      de Veleta, Spain, while snow samples from Mt. Neltner in the High Atlas
      mountains, contained resting spores of an orange-green colored Chloromonas sp.
      Other microbes observed in snow samples include bacteria, fungi, heterotrophic
      euglenids, diatoms, nematodes, and heterotrophic mastigotes (flagellated
      protists). This is the first report of snow algae from the Sierra Nevada
      mountains of Spain and from the Afro-alpine environment.

PMID- 10943391
TI  - Influence of the insecticide dimethoate on arbuscular mycorrhizal colonization
      and growth in soybean plants.
AB  - Application to the soil of the insecticide dimethoate had no effect on the growth
      of soybean colonized by the arbuscular mycorrhizal (AM) fungus Glomus mosseae and
      by the indigenous AM fungus. The application of the recommended concentration of
      dimethoate decreased the percentage of colonization of soybean by the indigenous
      AM population, but no significant effect was observed on the colonization of
      soybean inoculated with G. mosseae. The insecticide did not affect the
      germination of G. mosseae spores; however, 0.5 mg/l of dimethoate increased the
      germination of Gigaspora roseae and 5 mg/l of dimethoate decreased the
      germination of Scutellospora castaneae spores.

PMID- 10943392
TI  - Cesare Emiliani (1922-1995): the founder of paleoceanography.

PMID- 10943393
TI  - Basic research and the challenges of microbiology for the 21st century.

PMID- 10943395
TI  - A two-year walk with David Hopwood.

PMID- 10943394
TI  - David Hopwood and the emergence of Streptomyces genetics.
AB  - Streptomyces spp. are unusual among bacteria in growing as mycelial colonies with
      sporulating aerial hyphae. They are very important as the source of most of the
      major antibiotics. Pioneering work by David Hopwood in the 1950s and 1960s
      established Streptomyces coelicolor A3(2) as the model system for the genus.
      Since then he has led successive key phases of research on this organism. In the
      1970s, plasmids were discovered and characterised, and used both to establish
      conditions for transformation and in the subsequent development of cloning
      vectors. Protoplasts were exploited in both transformation and highly efficient
      cell fusion. In the 1980s, the early cloning of resistance genes from antibiotic
      producing strains was followed by the cloning of antibiotic biosynthetic gene
      clusters, and the development of general methods and probes for the cloning of
      such clusters from diverse species. Analysis of these gene sets led to wide
      ranging inferences about the biosynthesis of the important polyketide class of
      antibiotics, and to the production of hybrid antibiotics, and then, in the last
      decade, to more sophisticated combinatorial biosynthesis of designer molecules.
      In parallel, David Hopwood's work has also provided a crucial platform for
      studies of the regulation of the morphological and physiological differentiation
      that is manifested by sporulating antibiotic-producing colonies. Most recently,
      his involvement in the physical mapping of the entire 8 Mb genome of S.
      coelicolor A3(2) has culminated in its complete DNA sequencing: a project that
      should be completed under his management during the year 2000.

PMID- 10943396
TI  - Synthesis of the bacterial magnetosome: the making of a magnetic personality.
AB  - Magnetotactic bacteria synthesize intracellular, enveloped, single magnetic
      domain crystals of magnetite (Fe3O4, Fe2+Fe2(3+)O4) and/or greigite (Fe3S4)
      called magnetosomes. The magnetosomes contain well-ordered crystals that have
      narrow size distributions and consistent species- and/or strain-specific
      morphologies. These characteristics are features of a process called biologically
      controlled mineralization in which an organism exerts a great degree of
      crystallochemical control over the nucleation and growth of the mineral particle.
      Because of these features, the mineral particles have been used as biomarkers
      although not without controversy. These unique structures impart a permanent
      magnetic dipole moment to the cell causing it to align and swim along geomagnetic
      field lines, a behavior known as magnetotaxis. The apparent biological advantage
      of magnetotaxis is that it aids cells in more efficiently locating and
      maintaining position in vertical chemical gradients common in many natural
      aquatic environments.

PMID- 10943397
TI  - Bacterial symbioses. Predation and mutually beneficial associations.
AB  - The endosymbiotic theory, which has proved to explain the origin of mitochondria
      and chloroplasts, also posits the origin of nucleus and other cellular organelles
      that could have derived from ancient relationships among bacteria. It seems that
      predation might have been a prerequisite to the establishment of symbiosis as a
      source of evolutionary novelty. This review describes current different examples
      of bacteria able not only to attack and degrade other bacteria, but also to
      establish stable symbiotic relationships with different eukaryotic organisms.

PMID- 10943398
TI  - Characterization of beet necrotic yellow vein furovirus from Spanish sugar beets.
AB  - Rhizomania is a viral disease, caused by beet necrotic yellow vein furovirus
      (BNYVV), which was detected in Spanish sugar beets in 1988, it being focused on
      the Castilla y Leon region. BNYVV has five RNA fragments with specific functions,
      and the different composition and proportion of RNA in the virions allow their
      separation and the characterization of their activities during the development of
      the disease. Thirty-six samples of sugar beet rootlets and frozen pulps from
      three different sugar beet zones of Castilla y Leon were analyzed by DAS-ELISA
      and Immunocapture-Reverse Transcription-Polymerase Chain Reaction (IC-RT-PCR)
      using specific primers. The identity of the cDNA products was confirmed by nested
      PCR and restriction fragment length polymorphism (RFLP). The uniformity of the
      patterns obtained by RFLP analyses with nine endonucleases showed the existence
      of a unique strain of BNYVV in 80,000 Ha of crop surface which could be explained
      by a recent arrival of the rhizomania disease to this region. The isolates
      studied were more similar to type A, which has been previously described in
      BNYVV, but a non-expected cleavage site for this molecular group was observed
      with endonuclease HincII on the RNA-2 IC-RT-PCR product (nt 2133-3293) in the
      thirty-six Spanish samples and also in a North American strain taken as
      reference. The use of frozen pulps obtained as a previous step to the industrial
      extraction of sugar avoids problems due to erratic distribution of the virus in
      the roots, provides repetitive results for a particular sample, and facilitates
      epidemiological and distributional studies on rhizomania disease.

PMID- 10943399
TI  - Dinoflagellate chromosome behaviour during stages of replication.
AB  - In most dinoflagellate species, chromosomes are characterized by an almost
      continuous condensation of the nucleofilaments throughout the cell cycle and the
      absence of longitudinal differentiation as Q, G, or C banding. Their supercoiled
      architecture is maintained by divalent cations and structural RNAs. Their
      chromatin is devoid of histones and nucleosomes and their DNA composition is
      distinctive: in several species, more than 60% of thymines are replaced by a rare
      base, hydroxymethyluracil. We report here an immunofluorescence (conventional and
      confocal laser scanning microscopy, CLSM) and immunogold transmission electron
      microscopy (TEM) analysis of some stages of the early replication process in
      Prorocentrum micans dinoflagellate cells, after long pulse incorporation (3, 6 or
      9 days) with 50 micrograms/ml bromodeoxyuridine (BrdU) in the presence of 5
      fluoro-2'-deoxyuridine (FUdR) and BrdU antibody technique (BAT) detection. The
      large DNA content (45 pg per nucleus) of P. micans cells is compacted on 100
      chromosomes, 10 microns in length. In early S-phase, DNA replication sites are
      revealed as fluorescent domains organized in clusters, which appear in the
      periphery of the nucleus unlike other eukaryotes. In late S-phase, the number of
      labelled clusters increased; helically distributed, they did not appear
      synchronously in the whole chromosome. Under TEM, spherical domains of equivalent
      diameter appeared located all along the chromosomes after 6 days BrdU pulse.
      Replication occurs, but in our experimental conditions, segregation of daughter
      chromosomes was never observed. The blockade of the cell cycle after BrdU
      incorporation intervening just before the segregation of daughter chromosomes is
      discussed.

PMID- 10943400
TI  - Vertical migration behaviour of diatom assemblages of Wadden Sea sediments
      (Dangast, Germany): a study using cryo-scanning electron microscopy.
AB  - The vertical migration behaviour of diatom assemblages inhabiting Wadden Sea
      sediments near Dangast (Germany) was investigated using cryo-scanning electron
      microscopy. The diatom assemblages were dominated by small Navicula species.
      Intertidal sediments which were located at different distances from the high tide
      level or stayed submerged even throughout low tides were chosen. Samples were
      prepared and cryofixed in the field. Sampling was restricted to three sets: (i)
      before the onset of vertical migration, (ii) 3 to 5 h after the onset of vertical
      migration, and (iii) before the area became flooded again or just prior to dusk.
      The diatom assemblages inhabiting the different types of sediments did not always
      show the same response. When the tidal cycle exposed the sediment surfaces during
      the night cell densities increased in the early morning hours with the onset of
      light. Later on, although the photon flux density was still increasing, cell
      densities stayed constant or decreased before the water flooded the areas around
      noon. In experiments in which the water drained off around noon and the areas
      became exposed throughout the entire afternoon, cell densities increased even up
      to dusk when the photon flux density had dropped to values below 20 microM
      photons m-2 s-1. In an experiment in which the last sampling occurred at 10.15
      pm, when the photon flux density had already declined below 10 microM photons m-2
      s-1, cell densities had decreased to lower values. This was ca. 1 h before the
      area was flooded again. Finally, cryo-scanning electron microscopy revealed
      frequently occurring micro-patches of diatom assemblages which could be
      differentiated into typical areas of lower and higher cell densities further
      complicating the pattern of light or water cover induced movements.

PMID- 10943401
TI  - Evaluation of Xanthomonas campestris survival in a soil microcosm system.
AB  - Xanthomonas campestris pv. campestris is a pathogen of cruciferous plants. We
      studied the survival of the wild type strain and mutant derivatives which are
      deficient in exopolysaccharide (EPS) or in extracellular protease synthesis in
      soil microcosms in order to test the hypothesis that, in this environment,
      adherence to soil particles and scavenging of nutrients are very important
      strategies for bacterial survival. In sterile soil microcosms, differences in
      survival were only observed between the EPS producer and its mutant. In non
      sterile soil experiments, survival of Prt- mutant was similar to EPS- mutant,
      suggesting that both characteristics have a strong influence in survival in the
      presence of the natural bacterial community. Bacterial decrease represented by
      the slope of regression lines was higher in non-sterile soil microcosms due to
      the influence of biotic interactions.

PMID- 10943402
TI  - A rapid procedure for the isolation of plasmid DNA from environmental bacteria.
AB  - The INSTA-MINI-PREP method, a rapid protocol for plasmid DNA extraction, was
      originally developed to prepare plasmid DNA from 1 to 3 ml miniprep Escherichia
      coli cultures. Direct extraction of plasmid DNA is achieved by a two-phase
      solution which is separated by centrifugation in the presence of the INSTA-PREP
      gel barrier material. This method has been successfully tested on various
      environmental Salmonella strains, although it was not suitable for Pseudomonas
      aeruginosa and enterococci strains. The INSTA-MINI-PREP method is a new
      alternative procedure to screen plasmid contents of Salmonella and E. coli
      strains rapidly and easily.

PMID- 10943403
TI  - The key action cell factory, an initiative of the European Union.

PMID- 10943404
TI  - Microbial pathogenesis.

PMID- 10943405
TI  - Interactions between encapsulated Neisseria meningitidis and host cells.
AB  - A major feature of Neisseria meningitidis is its ability to invade human brain
      meninges. To access the meninges, the bacteria must cross the blood-brain barrier
      (BBB), which is one of the tightest barriers in the body. Therefore, N.
      meningitidis must have evolved some type of sophisticated means to bypass the
      physical properties of this cellular barrier. As N. meningitidis is encapsulated
      when present in the bloodstream, this review will focus on the mechanisms that
      encapsulated N. meningitidis has developed to interact with host cells and will
      suggest ways in which these mechanisms may be helpful for crossing the BBB.

PMID- 10943407
TI  - Intracellular parasitism and molecular determinants of Legionella virulence.
AB  - Bacteria of the genus Legionella are intracellular parasites and major human
      pathogens. They bind to surface receptors, penetrate eukaryotic cells and
      initiate complex disorders during phagocytosis. These disorders include
      inhibition of oxidative burst, a decrease in phagosome acidification, the
      blocking of phagosome maturation and changes in organelle trafficking. As a
      result, the microorganisms prevent the bactericidal activity of the phagocyte and
      transform the phagosome into a niche for their replication. Biological,
      biochemical and molecular-genetic approaches have been used to identify a panel
      of bacterial products that may be involved in Legionella virulence. They include
      cytotoxins, several enzymes and a set of genes thought to encode proteins of the
      export machinery. However, despite distinct progress in research, the molecular
      mechanisms underlying intracellular parasitism in Legionella are unclear.

PMID- 10943406
TI  - Molecular aspects of Bordetella pertussis pathogenesis.
AB  - The molecular mechanisms of Bordetella virulence are now well understood, and
      many virulence factors have been identified and characterized at the molecular
      level. These virulence factors can be grouped into two major categories:
      adhesins, such as filamentous hemagglutinin, pertactin and fimbriae, and toxins,
      such as pertussis toxin, adenylate cyclase, dermonecrotic toxin and tracheal
      cytotoxin. The production of most virulence factors is coordinately regulated by
      a two-component signal transduction system composed of the regulator BvgA and the
      sensor protein BvgS. The adhesins and toxins act in concert to establish
      infection. Some adhesins exert their effects synergically or are redundant
      functioning only in the absence of another adhesin, illustrating the importance
      of adhesion in infection. Most virulence factors are secreted into the culture
      supernatant or exposed at the surface of the bacterial cell. A notable exception
      is dermonecrotic toxin, which remains in the cytoplasmic compartment of bacterial
      cells. Most virulence factors are produced by all of the three major Bordetella
      species, B. pertussis, B. parapertussis and B. bronchiseptica. However, some,
      such as pertussis toxin and the tracheal colonization factor, are only produced
      by B. pertussis. Our understanding of Bordetella virulence at the molecular level
      has led to the development of new acellular vaccines against whooping cough, and
      of genetically attenuated B. pertussis strains to be used as recombinant live
      bacterial vaccine vectors for homologous and heterologous protection.

PMID- 10943408
TI  - Molecular mechanisms of malaria sporozoite motility and invasion of host cells.
AB  - Malaria sporozoites have the unique capacity to invade two entirely different
      types of target cell in the mosquito vector and the vertebrate host during the
      course of the parasite's life cycle. Although little is known about the specific
      interaction of the sporozoite with its target cells, two sporozoite proteins,
      circumsporozoite (CS) and thrombospondin-related adhesive protein (TRAP), have
      been shown to play important roles in the invasion of both cell types. CS protein
      is a multifunctional protein involved in sporogony, invasion of the salivary
      glands, the specific arrest of sporozoites in the liver sinusoid, gliding
      motility of the sporozoite, and hepatocyte recognition and entry. TRAP has been
      shown to be critical for sporozoite infection of the mosquito salivary glands and
      liver cells, and is essential for sporozoite gliding motility. This review will
      focus on the involvement of these molecules in sporozoite motility and the
      invasion of host cells.

PMID- 10943409
TI  - The Yersinia high-pathogenicity island.
AB  - A pathogenicity island present only in highly pathogenic strains of Yersinia (Y.
      enterocolitica 1B, Y. pseudotuberculosis I and Y. pestis) has been identified on
      the chromosome of Yersinia spp. and has been designated High-Pathogenicity Island
      (HPI). The Yersinia HPI carries a cluster of genes involved in the biosynthesis,
      transport and regulation of the siderophore yersiniabactin. The major function of
      this island is thus to acquire iron molecules essential for in vivo bacterial
      growth and dissemination. The presence of an integrase gene and att sites
      homologous to those of phage P4, together with a G + C content much higher than
      the chromosomal background, suggests that the HPI is of foreign origin and has
      been acquired by chromosomal integration of a phage. The HPI can excise from the
      chromosome of Y. pseudotuberculosis and is found inserted into any of the three
      copies of the asn tRNA loci present in this species. A unique characteristic of
      the HPI is its wide distribution in various enterobacteria. Although first
      identified in Yersinia spp., it has subsequently been detected in other genera
      such as E. coli, Klebsiella and Citrobacter.

PMID- 10943410
TI  - Functional organization of the gene cluster involved in the synthesis of the
      pneumococcal capsule.
AB  - Streptococcus pneumoniae is a major human pathogen and its capsular
      polysaccharide has been shown to be the main virulence factor. The molecular
      organization of the genes governing the formation of this capsule was not studied
      until the 1990s. The capsular clusters (cap) of eight of the 90 known
      pneumococcal types have now been studied. The cap operon, located between the
      dexB and aliA genes, is arranged as a central region comprising the genes coding
      for the specific-type polysaccharide, flanked by open reading frames that are
      mostly common to all of the serotypes. The biochemical functions of 24 genes
      required for capsular polysaccharide biosynthesis have been elucidated but the
      precise role of the flanking regions in capsular formation is unknown. The
      natural genetic transformation characteristic of pneumococci, the arrangement of
      the cap locus and the abundance of transposable elements at this locus favor the
      genetic variability of the capsule in this microorganism. These well-documented
      observations together with the finding that some genes located outside the cap
      cluster may also participate in capsule formation increase the complexity of
      pneumococcal infection control.

PMID- 10943411
TI  - The virulence plasmids of Salmonella.
AB  - Certain Salmonella serovars belonging to subspecies I carry a large, low-copy
      number plasmid that contains virulence genes. Virulence plasmids are required to
      trigger systemic disease; their involvement in the enteric stage of the infection
      is unclear. Salmonella virulence plasmids are heterogeneous in size (50-90 kb),
      but all share a 7.8 kb region, spv, required for bacterial multiplication in the
      reticuloendothelial system. Other loci of the plasmid, such as the fimbrial
      operon pef, the conjugal transfer gene traT and the enigmatic rck and rsk loci,
      may play a role in other stages of the infection process. The virulence plasmid
      of Salmonella typhimurium LT2 is self-transmissible; virulence plasmids from
      other serovars, such as Salmonella enteritidis and Salmonella choleraesuis, carry
      incomplete tra operons. The presence of virulence plasmids in host-adapted
      serovars suggests that virulence plasmid acquisition may have expanded the host
      range of Salmonella.

PMID- 10943413
TI  - Benjamin Elazari Volcani (1915-1999): sixty-three years of studies of the
      microbiology of the Dead Sea.

PMID- 10943412
TI  - Bacterial toxins modifying the actin cytoskeleton.
AB  - Numerous bacterial toxins recognize the actin cytoskeleton as a target. The
      clostridial binary toxins (Iota and C2 families) ADP-ribosylate the actin
      monomers causing the dissociation of the actin filaments. The large clostridial
      toxins from Clostridium difficile, Clostridium sordellii and Clostridium novyi
      inactivate, by glucosylation, proteins from the Rho family that regulate actin
      polymerization. In contrast, the cytotoxic necrotic factor from Escherichia coli
      activates Rho by deamidation and increases the formation of actin filaments. The
      enterotoxin of Bacteroides fragilis is a protease specific for E-cadherin and it
      promotes the reorganization of the actin cytoskeleton. The bacterial toxins that
      modify the actin cytoskeleton induce various cell disfunctions including changes
      in cell barrier permeability and disruption of intercellular junctions.

PMID- 10943415
TI  - Year's comments for 1999.

PMID- 10943414
TI  - Microbiological patents.

PMID- 10943416
TI  - Not plants or animals: a brief history of the origin of Kingdoms Protozoa,
      Protista and Protoctista.
AB  - In the wake of Darwin's evolutionary ideas, mid-nineteenth century naturalists
      realized the shortcomings of the long established two-kingdom system of
      organismal classification. Placement in a natural scheme of Protozoa, Protophyta,
      Phytozoa and Bacteria, microorganisms that exhibited plant-like and animal-like
      characteristics but obviously differed in organization from larger plants and
      animals, challenged traditional classification. The attempts of naturalists to
      classify these organisms outside the constraints of the plant and animal kingdoms
      led to concepts of additional kingdoms (Protozoa, Protista, Protoctista, etc.) to
      accommodate the nature of these organisms as not true plants or animals.

PMID- 10943417
TI  - Isolation and typing methods for the epidemiologic investigation of
      thermotolerant campylobacters.
AB  - Thermotolerant campylobacters, C. jejuni, C. coli, C. lari and C. upsaliensis,
      are spiral bacteria involved in human enteric disease. The prevalence of these
      emerging pathogens, mainly C. jejuni and to a lesser extent C. coli, as etiologic
      agents of enteric disease in industrialized countries has increased over the last
      decade. The isolation and culture of these microorganisms is tedious and time
      consuming mainly due to their complex nutritional and environmental requirements.
      This review discusses the techniques and methods developed for the selective
      isolation of thermotolerant campylobacters from food, environmental and clinical
      samples. Additionally, both traditional and newer molecular biology techniques
      applied to this group of thermophilic organisms for typing and taxonomic purposes
      are summarized.

PMID- 10943418
TI  - Enumeration and isolation of viral particles from oligotrophic marine
      environments by tangential flow filtration.
AB  - A method for concentrating, enumerating and isolating viral particles from marine
      water samples was developed and evaluated. The method consists of a concentration
      step by a tangential flow filtration (TFF) system, ultrafiltration by centrifugal
      concentrator, and visualization by transmission electron microscopy (TEM). This
      procedure allows to reduce volumes of ca. 21 of seawater to 10-20 microliters,
      which can be dispensed on electron microscopy grids to count total viral
      particles. This method allows the recovery of small numbers of viral particles
      from oligotrophic seawater samples, in which viral numbers ranged from 10(5) to
      10(6) viral particles/ml. The tangential flow filtration system was evaluated as
      quantitative technique using suspensions of two different bacteriophages (T6 and
      phi X174) in autoclaved seawater. Recovery rates varied depending on both the
      viral morphology and flow rate; recovery percentages reached 117.4% for T6 and
      60.6% for phi X174 using low flow rate.

PMID- 10943419
TI  - Light absorption by phototrophic bacteria: effects of scattering, cell
      concentration and size of the culture vessel.
AB  - This article analyzes how absorption of light by suspensions of phototrophic
      bacteria is modulated by changes in the biomass of the culture, the size of the
      culture vessel and by the presence of refractile structures within the cells.
      Increases in biomass and culture size result in higher rates of light absorption
      but in the decrease of the amount of energy available per cell. The presence of
      refractile structures has different consequences depending on the biomass
      concentration. In dense cultures, the accumulation of refractile structures
      increases the reflection of light, and also reduces specific light absorption. In
      diluted cultures, however, the effect is the opposite, and refractile structures
      seem to increase light absorption.

PMID- 10943420
TI  - Identification of synergistic interactions among microorganisms in biofilms by
      digital image analysis.
AB  - Digital image analysis showed that reductions in biofilm plating efficiency were
      due to the loss of protection provided by two benzoate-degrading strains of
      Pseudomonas fluorescens. This loss in protection was due to the spatial
      separation of the protective organisms from benzoate-sensitive organisms during
      the dilution process. Communities were cultivated in flow cells irrigated with
      trypticase soy broth. When the effluent from these flow cells was plated on 0.15%
      benzoic acid, satellite colonies formed only in the vicinity of primary colonies.
      A digital image analysis procedure was developed to measure the size and spatial
      distribution of these satellites as a function of distance from the primary
      colony. The size of satellites served as a measure of growth, and the number per
      unit area served as a measure of survival. At the three dilutions tested, the
      size and concentration of satellite colonies varied inversely with distance from
      the primary colonies. When these measurements were plotted, the slopes were used
      to quantify the effect of bacterial association on the growth and survivability
      of the satellites. In the absence of the primary colonies, satellites grew in
      axenic culture only at low benzoate concentrations. Thus benzoate-degrading
      organisms are capable of creating a protective microenvironment for other members
      of biofilm communities.

PMID- 10943421
TI  - Study of lichens with different state of hydration by the combination of low
      temperature scanning electron and confocal laser scanning microscopies.
AB  - The use of techniques such as low temperature scanning electron microscopy
      (LTSEM) and confocal laser scanning microscopy (CLSM) allows the study of lichen
      thalli in different states of hydration and also near the natural state. The
      spatial organization of desiccated thalli, with reduced, very compact algal
      layers, is different from that of hydrated ones. Sometimes, the observation with
      transmission electron microscopy (TEM) of photobiont pyrenoids from desiccated
      thalli reports pyrenoids with a central part of a weak stained matrix lacking
      pyrenoglobuli, named "empty zones". "Empty zones" are not distinguishable with
      LTSEM and do not present immunolabelling with rubisco antibody in TEM. These
      zones could be originated by an expansion process during rehydration produced in
      chemical fixation.

PMID- 10943422
TI  - Aerobic and facultative anaerobic heterotrophic bacteria associated to
      Mediterranean oysters and seawater.
AB  - A comparative study on the composition and seasonal fluctuations of the main
      heterotrophic bacterial groups and species isolated from Mediterranean oysters
      and their growing-seawater was carried out. For the study we used 574 strains
      isolated from Marine Agar (MA) and submitted to numerical analysis of phenotypic
      traits in previous studies, plus 323 isolates recovered on Thiosulphate Citrate
      Bile Sucrose (TCBS) agar from the same samples and identified in this study.
      Oyster samples were dominated by halophilic fermentative bacteria during most of
      the year with predominance of two Vibrio species, V. splendidus (at temperatures
      lower than 20 degrees C), and V. harveyi (at higher temperatures). On the
      contrary, Vibrio spp. was not the predominant microbiota of seawater, where most
      isolates had remained unidentified but corresponded to alpha-Proteobacteria, as
      shown by rDNA hybridization with phylogenetic probes in this study. Among the
      strict aerobes that could be identified, none of them showed a clear dominance,
      and many different groups were represented in very low percentages, in contrast
      with the major species from oyster samples. Shannon-Weaver diversity index
      revealed significant differences between both types of samples. No apparent
      seasonality was found in the distribution of seawater species, in sharp contrast
      with oyster-associated bacteria.

PMID- 10943423
TI  - Characterization of Bacillus strains of marine origin.
AB  - A total of twenty aerobic endospore-forming bacilli, isolated from marine
      invertebrates and sea water of different areas of the Pacific Ocean, were
      taxonomically characterized. Most of the bacilli (11 strains) of marine origin
      belonged to the species Bacillus subtilis, according to their phenotypic
      characteristics, antibiotic susceptibility profiles, and fatty acids patterns. A
      group of four alkaliphilic strains formed a separate cluster that was tentatively
      classified as B. horti. One isolate, KMM 1717, associated with a sponge from the
      Coral Sea was identified as B. pumilus. Two strains, Bacillus KMM 1916 and KMM
      1918, showed antibiotic sensitivity profiles similar to B. licheniformis, but
      they had a distinct fatty acid composition and peculiar phenotypic traits. The
      taxonomic affiliation of KMM 1810 and KMM 1763 remained unclear since their fatty
      acid composition and antibiotic sensitivity patterns were not resembled with none
      of these obtained for Bacillus strains.

PMID- 10943424
TI  - The bicentennial of a forgotten giant: Lazzaro Spallanzani (1729-1799).

PMID- 10943425
TI  - The Baltimore affair: a different view.

PMID- 10943426
TI  - The HIV challenge to breastfeeding.

PMID- 10943427
TI  - HIV and infant feeding: to breastfeed or not to breastfeed: the dilemma of
      competing risks. Part 2.
AB  - The discovery of the human immunodeficiency virus (HIV) in breastmilk in 1985,
      and subsequent research, supports the hypothesis that breastfeeding provides a
      route of transmission to the nursing baby. Various routes of infection and
      relative rates of transmission have been studied in many parts of the world,
      leading to the blanket guideline that babies of HIV-infected mothers should not
      be breastfed, if a safe alternative can be provided. However, due to the limits
      inherent in various studies and various testing methods, the exact frequency of
      breastmilk transmission of HIV during the course of lactation remains unknown,
      and the conclusions drawn are thus conflicting and confusing. Replacement feeding
      of young babies with non-human milks and other foods may be hazardous in poverty
      stricken populations in Africa and elsewhere, and still more research suggests
      that there are several properties in human milk that may provide specific
      protection to the baby of an infected mother. The possibility of providing the
      mother's own treated expressed breastmilk to the baby at risk of HIV infection
      via breastfeeding is an alternative which has yet to be fully explored and ways
      that this could be accomplished are examined. Those of us working with mothers
      and babies need more information before we can assist mothers living with HIV to
      make truly informed decisions about the safest way to feed their babies. Topics
      requiring urgent further attention are outlined.

PMID- 10943428
TI  - Breastfeeding--natural fertility control/LAM: an effective option?

PMID- 10943429
TI  - Breastmilk and infection--a brief overview.

PMID- 10943430
TI  - Ready for birth--but what about breastfeeding?
AB  - This paper examines and discusses a range of influences on the experience of
      breastfeeding. Primarily, the impact of antenatal education, the experience of
      labour, birth and postnatal problems on the initiation and duration of
      breastfeeding are discussed.

PMID- 10943431
TI  - Toxic, bioaccumulative and persistent chemicals in central and eastern Europe-
      state-of-the-art report.
AB  - Organic substances that are persistent, bioaccumulative and have toxic
      characteristics likely to cause adverse effects on human health or have
      environmental effects are called PBTs (Persistent, Bioaccumulative, Toxic
      substances). The report "Persistent, Bioaccumulative and Toxic Chemicals in
      Central and Eastern European Countries--State-of-the-art Report" was prepared by
      a group of scientists from the Czech Republic, Slovakia, Poland and Estonia and
      was published on the Internet (http:?recetox.chemi.muni.cz/).

PMID- 10943432
TI  - Comparing evaluation about the occurrence of persistant organic-chemical
      compounds in Bavaria and the Czech Republic.
AB  - From 1995 to '97 Bavarian Ministry sponsored a voluminous project to evaluate
      data in literature and other non published data from agencies concerning to POP's
      in order to compare the environmental situation in both countries.

PMID- 10943433
TI  - Occurrence of persistent organic pollutants (PAHs, PCDD and PCDF) in fly ash
      generated in coal-fired thermal and power plants in Silesia, Poland.

PMID- 10943434
TI  - Polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans in soil samples
      from selected industrial and airport areas in Croatia.

PMID- 10943435
TI  - Polychlorinated naphthalenes in soil, sediment, and biota collected near a former
      chloralkali plant in coastal Georgia, USA.
AB  - Concentrations of total polychlorinated naphthalenes (PCNs) as high as 23
      micrograms/g, dry wt, were found in sediments contaminated by the disposal of
      wastes from chlor-alkali processes. Concentrations of total PCNs in blue crab,
      fish and birds were 3- to 5-orders of magnitude less than that in sediments. The
      profile of PCN congeners in biota was predominated by tetra- or penta
      chloronaphthalenes, while hepta- and octa-chloronaphthalenes were dominant in
      sediments. The 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) estimated
      for PCNs in sediments and biota were greater than those reported for PCBs, PCDDs
      or PCDFs. These results suggest that chlor-alkali process is a source of PCNs
      found in the environment.

PMID- 10943436
TI  - The evaluation of dioxin emissions from pilot scale incineration of
      organochlorine compounds.
AB  - Formation of the dioxins was investigated in case of two fuel types (kerosene
      dichlorobenzene and kerosene-dichloroethane) on a pilot scale liquid waste
      incinerator. It was determined the effect of the molecule structure (aromatic,
      aliphatic) and Cl content (1, 3 and 6%) of the liquids and the combustion
      parameters (O2 content, residence time and temperature). In some experiments
      particulate matters (fly ash and soot) were injected. The measured dioxin
      concentrations ranged up to 160 ng/Nm3 or till 10 ng/Nm3 TEQ, except at addition
      of soot where extremely high dioxin concentrations (up to 750 ng/Nm3, or 30
      ng/Nm3 TEQ) were measured. Main conclusions of the experiment are: The
      incineration of aromatic chlorinated products produce almost 10 times higher
      dioxin concentrations than the aliphatic ones. A relatively low dioxin
      concentration is caused at low (1 to 3%) feed Cl contents while over a threshold
      value of more than 3% Cl intensifies sharply the dioxin formation. The dioxin
      generation can be characterized with concentrations measured at 600-650 degrees
      C. Dioxin toxicity reduction occurs when cooling down to 200-250 degrees C.
      Changes between these sampling temperatures can be explained mostly by sorption
      phenomena occurring between dioxin content of flue gases and solid deposits.

PMID- 10943437
TI  - Metabolism and activation of polychlorinated biphenyls (PCBs).

PMID- 10943438
TI  - Mechanisms of toxicity of PCB metabolites: generation of reactive oxygen species
      and glutathione depletion.

PMID- 10943439
TI  - Effect of PCBs on the activation of the transcription factors AP-1 and NF-kappa
      B.

PMID- 10943441
TI  - The effect of selected scavengers on radiolytic degradation of 2,4-dichlorophenol
      for environmental purposes.

PMID- 10943440
TI  - Effects of lipids and antioxidants on PCB-mediated dysfunction of vascular
      endothelial cells (EC).
AB  - Our findings suggest that exposure to specific environmental contaminants can
      trigger diseases of the vasculature, e.g., cardiovascular disease. In addition,
      high-fat diets may potentiate and diets high in antioxidant nutrients may protect
      against PCB-mediated endothelial cell dysfunction. Our data give an insight into
      the potential use of vitamin E and related antioxidants to limit PCB-mediated
      cell injury. These studies are significant for providing new insights into
      potential nutrition interventions in diseases that can be induced by the toxicity
      of PCBs and other halogenated compounds.

PMID- 10943442
TI  - Long-term potentiation in CA1 region of rat brain slices is blocked by PCB 153.

PMID- 10943443
TI  - Human health effects of polychlorinated biphenyls.

PMID- 10943444
TI  - Levels of PCBs, PCDDs and PCDFs in human milk of mothers living in four districts
      of the Czech Republic.

PMID- 10943445
TI  - Organochlorine pesticides residues in human breast adipose tissue in Poland.

PMID- 10943446
TI  - Persistent polychlorinated compounds in foods in Hungary.

PMID- 10943447
TI  - Evaluation of cytotoxicity, dioxin-like activity and estrogenicity of complex
      environmental mixtures.
AB  - Complex organic extracts from soils and sediments collected in an industrial
      region of the Czech Republic were tested with in vitro recombinant cell lines for
      their potential dioxin-like and estrogenic activity and cytotoxicity. For dioxin
      like toxicity tested on H4IIE-luc cells complete dose-responses were obtained
      with all extracts. The MCF-7-luc cell line used for determination of estrogen
      receptor-mediated activity was sensitive to the cytotoxic effects of the soil and
      sediment extracts. Dose dependent cytotoxicity was observed with most samples.
      Significant estrogenic activity was found in all samples. The toxic or estrogenic
      equivalents based on the analytically determined concentrations of organic
      pollutants with known dioxin-like or estrogenic potency were calculated and
      compared to the bioassay-derived estimates. Fractionation along with mass-balance
      calculation enabled identification of the most active fraction and classes of
      compounds. Polycyclic aromatic hydrocarbons were identified as the group of
      compounds responsible for most of the TCDD-like activity as well as for important
      portion of estrogenic activity.

PMID- 10943448
TI  - Effect of PCB 118 on the filtering behaviour of the freshwater mussel Anodonta
      cygnaea L.

PMID- 10943449
TI  - Vertical profile of dioxin-like and estrogenic potencies in a sediment core from
      Tokyo Bay, Japan.
AB  - Dioxin-like and estrogenic activities were measured in a sediment core collected
      from Tokyo Bay using in vitro bioassays after fractionating sediment extracts
      into three fractions by florisil column chromatography. Target analytes including
      polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polycyclic
      aromatic hydrocarbons (PAHs) and nonylphenol (NP) were measured by gas
      chromatography-mass spectrometry (GC-MS) or high performance liquid
      chromatography (HPLC) techniques. NP concentrations were greater in surface
      sediments (0 to 12 cm) than those in sub-surface (12-30 cm). The maximum observed
      PCN concentration was 5 ng/g, whereas that of PCBs was 300 ng/g. Concentrations
      of PCBs in fraction 1 (F1) were not high enough to induce significant luciferase
      activities in H4IIE-luc cells. Significant dioxin-like activities were found in
      fractions 2 (F2) and 3 (F3). PAH concentrations were correlated with dioxin-like
      activities measured in F2. Compounds that contribute to the dioxin-like
      activities in F3 were not identified yet. Significant estrogenic activities were
      observed in F2 samples, which may be related to the presence of certain
      estrogenic PAHs. F3 samples were cytotoxic to MCF-7 cells and therefore their
      estrogenic potential could not be estimated.

PMID- 10943450
TI  - Organochlorine pesticides as endocrine disruptors in wildlife.
AB  - Many xenobiotic compounds introduced into the environment by human activity have
      been shown to adversely affect wildlife. The ubiquitous distribution of many
      contaminants and the documented, nonlethal, multigenerational effects on the
      reproductive, endocrine, and immune systems have lead to concerns that wildlife
      worldwide are affected. The reproductive disorders reported to date in wildlife
      include reduced fertility, reduced hatchability, reduced viability of offspring,
      impaired hormone secretion or activity and modified reproductive anatomy. The
      endocrine system exhibits an organizing effect on the developing embryo. Thus, a
      disruption of the normal hormonal signals can permanently modify the organization
      and future function of the reproductive system. An understanding of the
      developmental consequences of endocrine disruption in wildlife can lead to new
      indicators of exposure to endocrine disrupting contaminants. Thus, wildlife serve
      as important sentinels of ecosystem health, including human public health. An
      ecoepidemiological approach examining wildlife reproductive abnormalities
      combined with traditional toxicological studies identifying causation can provide
      the best model for predicting ecosystem concerns due to environmental
      contamination.

PMID- 10943451
TI  - Primary mono-layer cell cultures as model system for studying of environmental
      toxic agents: organochlorine compounds.
AB  - Organic pollution of water and soil has various harmful effects on biological
      systems (1). Chlorine substituted benzol compounds are one these xenobiotic
      substances, which are toxic to the environment (2). They can also accumulate in
      plant and animal tissues (3), which provides ample reason to study the effects of
      sublethal doses of chloro-benzols on various cell cultures. In this study the
      toxic effects of chloro-benzols were investigated on avian fibroblast and
      mammalian hepatocyte cultures. The fibroblast cultures were prepared from eggs
      preadapted to chloro-benzol during a fourteen-day-long incubation period. The
      Wistar rat hepatocyte monolayer cultures were exposed to a direct treatment of
      1,2,4-tri-chloro-benzol (0.01 microgram/ml-1 microgram/ml) for 3 hours. Following
      the treatment with chloro-benzol, the viability of the cells was measured,
      together with lactic dehydrogenase activity, in both kinds of cultures. The
      effect of tri-chloro-benzol treatment on chicken eggs was not significant. The
      cells of chicken embryos were not damaged after the 1,2,4-tri-chloro-benzol
      treatment. The hepatocyte cultures showed the toxic effects of 1,2,4-tri-chloro
      benzol after the direct and acute treatment. The cell viability decreased and the
      LDH activity increased significantly. These results show that the primary cell
      cultures are suitable for studying the effects of organochlorine compounds.

PMID- 10943452
TI  - Chloride ions formation during degradation of organochloride compounds using TiO2
      deposited on glass microspheres.
AB  - Aqueous solutions containing 200 mg/dm3 of p,p'-DDT and methoxychlor were
      photodegraded for 60 min in UV/TiO2/O2 system and chloride ions concentration and
      pH were measured. From 60 to 80% of the investigated pesticides were eliminated
      after treatment. Over 27% of chlorine atoms were splitted off for methoxychlor
      and 10% for p,p'-DDT. The experimental data suggest, that chlorine atoms were
      removed from the -CCl3 moiety but the chlorine atoms bound to aromatic ring were
      left intact at this step of photodegradation.

PMID- 10943453
TI  - Pine needles as biomonitoring indicator of organochlorine compounds pollution in
      Croatia.

PMID- 10943454
TI  - Toxicity of chlorinated phenolic compounds occurring in pulp mill effluents.

PMID- 10943455
TI  - Natural degradation of organochloride compounds in some Romanian surface waters.

PMID- 10943456
TI  - Exposure assessment: forgotten component of risk assessment.

PMID- 10943458
TI  - The impacts of exposure to organic compounds occurrence of natural origin in
      thermal water on health in Bekes, Hungary.
AB  - Deep thermal well (75 degrees C) in Bekes county, South East Hungary has been
      studied. The chemical measurements showed that the thermal water coming from deep
      geological layers (> 800 m) contains up to 117.2, 35.2, 30.2 and 26 micrograms/l
      of benzene, toluene, ethylbenzene, and xylenes, respectively. The objectives of
      this study are: to measure these naturally occurring compounds; estimating to
      potential risk and hazard index for the population who are using this well mainly
      for swimming and health baths; assessing the relationship between exposure to
      environmental chemical and human health; and to stimulate thinking about possible
      broader uses of risk assessment in identifying and solving public health
      problems. This paper is not intended as a complete study concerning the four
      measured compounds. A particular emphasis on benzene which is highly toxic and
      carcinogenic has been paid. The exposure assessment of benzene based on Risk
      Assistant model was done. The results showed that the Hazard Quotient (H.Q.) for
      benzene is more than 1 (requiring actions) and the probability of getting cancer
      from this exposure is 8E-5 exhibiting high risk for exposed population.

PMID- 10943457
TI  - Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls
      (PCBs): implications for risk assessment.
AB  - Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative and toxic
      contaminants in the environment. Individual PCB congeners exhibit different
      physico-chemical properties and biological activities which result in different
      environmental distributions and toxicity profiles. The variable composition of
      PCB residues in environmental matrices and their different mechanisms of
      toxicity, complicate the development of scientifically based regulations for the
      risk assessment. Various approaches for the assessment of risks of PCBs have been
      critically examined. Recent developments in the toxic equivalency factor (TEF)
      approach for the assessment of toxic effects due to dioxin-like PCBs have been
      examined. PCB exposure studies which describe non-dioxin-like toxic effects,
      particularly neuro-behavioral effects and their effective doses in animals were
      also considered. A comparative assessment of effective doses for dioxin-like and
      non-dioxin-like effects by PCBs was made to evaluate the relative significance of
      non-ortho and ortho-substituted PCBs in risk assessment. Using mink as an
      example, relative merits and implications of using TEF and total PCB approaches
      for assessing the potential for toxic effects in wildlife was examined.

PMID- 10943459
TI  - Human health risk assessment and management in hazardous waste site contaminated
      by polychlorinated benzenes.
AB  - The improper management of large quantity of chemical waste of a chemical plant
      caused considerable soil contamination on a temporary hazardous waste disposal
      site. Initial and action-oriented exposure and health risk assessment was carried
      out in early 90's. The dominant contaminants were tetrachlorobenzenes (TeCBs),
      pentachlorobenzene and hexachlorobenzene (HCB). Concentration of TeCBs in top
      soil layer and vadoze zone exceeded several g/kg. After taking appropriate
      technical measures quantitative health risk assessment was performed for the
      target population living in the surrounding settlements. Health risk estimates to
      HCB ingested or inhaled with suspended dust and soil particulates showed that
      carcinogenic risk values lower than 10(-6) i.e. below the acceptable risk. For
      other chlorobenzenes that cause non-cancer toxic effects risk quotients showed
      marked health hazard inside the dump and small potential risk in vicinity.
      However, this assessment is based on limited monitoring data, additional
      information is needed to substantiate this conclusion.

PMID- 10943460
TI  - Hazardous waste as environment pollutant and risk factor of employees.

PMID- 10943461
TI  - Elements referring to Romanian regulations for risk assessment of environmental
      chemicals.

PMID- 10943462
TI  - Risk assessment of manganese.
AB  - The concentration of manganese was determined in the work environment of eight
      enterprises by welding and metal processing (198 samples) as well as in
      biological samples (blood, hair) of workers (180 samples). Industrially exposed
      individuals had significantly higher levels of manganese in blood and hair than
      the control group--7.6 times higher in blood and 3.2 times higher in hair.
      Neurobehavioral examination was performed by physician and specific questionnaire
      (Q16) containing 16 "yes" or "no" items relating to neuropsychiatric symptoms. It
      is possible to use the level of manganese in biosamples as the indicator of
      health risk by occupationally exposed individuals.

PMID- 10943463
TI  - Sensitivity analysis of risk assessment programs to various input parameters.
AB  - HESP 2.b risk assessment program was studied in detail concerning the effect of
      changing different input parameters for the output ADI values calculated by the
      program. We used the standard Netherlands 1.0 scenario offered by the program.
      With this we fixed a lot of input parameters which define the area, human and
      animal recipient parameters etc. The remaining 31 unfixed parameters were fixed
      at first to "BASE" input values and the BASE output values were calculated by
      HESP. Later we chose only one parameter at a time and changed it to an another
      value. The calculated ADI values were then compared to BASE output values. Seven
      parameters (soil type, soil usage, site length, soil pH, groundwater fraction in
      drinking water, basement floor type and Qev) were studied. We found, that
      changing soil pH or Qev have not any influence on the output ADI values in case
      of any contaminant. Soil type change has not any effect on the output ADI value
      in case of Pb or Cd but it seems to play important role in all cases of the four
      organic material we investigated. Changing soil usage have influence on the
      output ADI value almost in every case. It seems to be linear relation between the
      maximal concentration of contaminant and calculated ADI. Changing the site length
      and basement floor type gave in some cases different ADI values compared to BASE
      values. If we alter the groundwater fraction in drinking water we got usually
      different ADI values. With Risc Human risk assessment program we got similar
      results: nor the changes in soil type, site diameter or soil pH gave any changes
      in output ADI values. Our results hint that using HESP and Risc Human requires
      enhanced caution.

PMID- 10943464
TI  - Organochlorine pesticides in Bulgaria--regulatory aspects and exposure.

PMID- 10943465
TI  - Risk assessment of some agrochemicals on earthworms.

PMID- 10943466
TI  - On the role of animal models in risk assessment of neurotoxic pesticides.
AB  - A complication is given on the elements of risk assessment of hazardous
      neurotoxic pesticides, using data from human epidemiological studies, as well as
      animal experiments. Well-controlled laboratory studies of neurotoxicity have the
      potential to provide adequate exposure and effect data for accurate hazard
      identification. Using animal models of neurotoxicity as highly sensitive
      behavioral and neurophysiological methods as a function of doses, provide data
      for human low dose extrapolation by mathematical models. To reduce risk ("risk
      management") some examples are given how to handle properly neurotoxic pesticides
      with high risk.

PMID- 10943467
TI  - Overview of insecticide toxicity.

PMID- 10943468
TI  - A broad-based evaluation of pesticide-exposed children.
AB  - Research tends to center on the individual exposed to endocrine disruptors,
      frequently using a disease centered medical model for evaluative purposes.
      Pesticides, like many other contaminants, disrupt the endocrine system. A
      normative growth and developmental model was used to evaluate four- and five-year
      old Mexican children living in agricultural areas relying on the use of
      pesticides and compared the children to those living in a non-agricultural
      community. The purpose was to determine if the children of any given community
      were at risk from exposure, in contrast to identifying specific children with
      multiple deficits. Anthropological methods were adapted to provide a rapid
      community assessment approach. Living conditions, social and cultural conditions
      and genetics were similar in all groups studied. Growth, in terms of height and
      weight were alike for children in both areas. Differences existed in
      developmental skills, as measured through play behaviors. Neuro-muscular
      deficits, in terms of coordination and stamina, were found with the children in
      the agricultural communities. The heavier exposed children also exhibited neuro
      mental deficits, as measured through the use of drawing and memory problems. No
      child excelled or performed poorly on all activities. One important outcome of
      the study was that behavior standards designed for American children did not
      always apply to these children due to different expectations placed on the child.
      Future research needs to examine if other endocrine disrupting compounds create
      similar developmental deficits.

PMID- 10943469
TI  - Small subchronic doses of the pesticide dimethoate and/or cadmium and lead
      treatment causes disturbances in the chromosomes of young rats.
AB  - Small doses of Dimethoate (DM) and cadmium (Cd) which in themselves proved to be
      harmless in causing chromosome aberrations, potentiate each other's toxic effect
      concerning both numerical and structural aberrations caused in rat bone marrow
      cells. The toxic effect of lead (Pb) was not enhanced by DM.

PMID- 10943470
TI  - Analytical and biological data to the environmental-toxicological behaviour of
      Verbutin pesticide.
AB  - Ecotoxicological characteristics of a new insecticide synergist, MBB-599
      (proposed common name: Verbutin) was investigated. The studies included the
      determination of the hydrolysis, the biodegradability, the adsorption and
      desorption characteristics in soil and the effects on living systems (bacterium,
      alga, Daphnia, and fish) as well.

PMID- 10943471
TI  - Evaluation of a Hungarian acaricide original molecule based on its environmental
      toxicological studies.
AB  - The results of the environmental toxicological investigations and their results
      of a new hungarian acaricide molecule (SZI-121) developed by the CHINOIN were
      summarized. The toxicological effects of the test item on different
      ecotoxicological test systems were investigated in the following tests:
      Bacterium, alga, and plant growth inhibition tests, acute immobilization and 21
      days reproduction tests on Daphnia magna, acute fish test, closed bottle test,
      mobility, aerob degradation and adsorption/desorption tests on three different
      soils. No toxic effect was found in the bacterium, alga, plant growth inhibition
      and acute fish tests in the highest concentrations used. In the Daphnia
      immobilization test 0.14 mg/l LC50 value was established in the concentration
      range of 0.0128-40 mg/l applied. The test item showed similar characteristics as
      the reference item during the mobility test in soils, the adsorption/desorption
      study and the degradation investigations. In order to determine the environmental
      degradation rate further degradation investigations, as well as the nitrogen
      mineralization test and the model of concentration change in natural waters were
      performed.

PMID- 10943472
TI  - Experimentally induced functional changes of the nervous system caused by
      subchronic combined administration of heavy metals and an organophosphate
      pesticide.

PMID- 10943473
TI  - Results of the general toxicity and genetic studies of an insecticide
      intermediate.
AB  - Methyl-chrysanthemate is one of the intermediates of pyrethroid type
      insecticides. The acute toxicity of the test item was investigated in rats after
      single oral, dermal and inhalation applications. The irritation effect was
      determined by Draize method. Buehler method was applied to evaluate the
      sensitization potential of the test item. The mutagenic effect was assessed on
      Salmonella typhimurium strains. Furthermore metaphase chromosome aberration assay
      was performed on CHO cell line to check the structural chromosome aberrations.

PMID- 10943474
TI  - Histological examination of CAM treated with irritative pesticides.
AB  - The potential irritancy of compounds may be detected by observing adverse changes
      which occur in the chorioallantoic membrane (CAM) of the egg after exposure to
      tested chemicals. In our experiment irritating pesticides (Fusilade S, Karathene
      LC) and a technical component of pesticide (Trend) are tested and their effects
      are examined on tissue structure of CAM. After 10-11 days of incubation of
      chicken embryos the chorioallantoic membrane becomes trilaminar. The outer layer
      is chorionic epithelium between the two rows of cuboidal cells, thin-walled
      vascular sinuses can be found. In the intermediate layer, the mesenchyme, well
      developed blood vessels can be seen. The inner layer is formed by allantoic
      epithelium. After the treatment with Fusilade S the wall of the blood vessels was
      damaged, and blood diffused from the blood vessels. After the treatment with
      Karathane LC rupture of the wall of the blood vessels could be seen and blood
      appeared around the blood vessels. Blood vessels of the yolk sac were frequently
      damaged under CAM.

PMID- 10943475
TI  - Parental education as a confounder in the assessment of low level lead effect on
      psychological functions in children.

PMID- 10943476
TI  - Behavioural effects of subchronic lead treatment in combination with ethanol in
      rats.
AB  - The effect of lead acetate administration during perinatal (1. prenatal, 2.
      prenatal and suckling period, 3. prenatal + suckling period + 4 weeks after
      weaning) development in combination with ethanol was investigated in Wistar rats
      at the age of 12 weeks on open-field behaviour and auditory startle response.
      Lead intoxication has on the investigated behavioural parameters the most
      pronouncing effect when applied during the days 5-15 of pregnancy.

PMID- 10943477
TI  - Acute pulmonary effects of single intratracheal exposure to metallic sulphates in
      rats.

PMID- 10943478
TI  - Effects of chronic, intrauterine organic and inorganic mercury intoxication on
      the epileptogenicity of developing rat.

PMID- 10943479
TI  - Effect of chronic low-dose developmental methylmercury intoxication on
      epileptogenicity in rats.

PMID- 10943480
TI  - Acute effects of inhalation exposure to organic solvents in rats.

PMID- 10943481
TI  - Role of environmental factors on the reproducibility of Lemna test.

PMID- 10943482
TI  - Conventional and alternative acute oral toxicity tests in toxicological practice.

PMID- 10943483
TI  - Muta Mouse--validation studies.

PMID- 10943484
TI  - Studies on the toxic interaction between monensin and tiamulin in rats.

PMID- 10943485
TI  - Carcinogenicity of medicinal drugs: a survey of IARC monographs.

PMID- 10943486
TI  - Application of GC-FID and GC-MS for assessing PAHs in suspended dust.
AB  - The social concern about polycyclic aromatic hydrocarbons (PAHs) is due to the
      awareness that several of them are carcinogens and are present in polluted air.
      Several epidemiological investigations have tried to assess the influence of air
      pollution on the incidence in the population (1). Some authors have suggest that
      1-10% of the incidence of lung cancer is caused by air pollution (2, 3). Several
      sources, e.g. traffic, oil heating, wood stoves, industry may contribute PAHs to
      the air pollution. Therefore continuous air pollution control applying selective
      and precise analytical procedures is needed. The submitted work presents results
      of examination of sixteen polycyclic aromatic hydrocarbons [naphthalene,
      acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene,
      pyrene, chrysene, benzo(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene,
      benzo(a)pyrene, indeno(1,2,3-cd)pyrene, dibenzo(a, h)anthracene,
      benzo(ghi)perylene] settled on particles of 10 microns fractions of ashes,
      emitted from industrial and communication sources. Samples of suspended dust were
      collected at twelve measuring points, from May to June 1998, in 24-hour cycles,
      in accordance with US EPA methodology. PAHs were extracted from suspended dust in
      a Soxhlet apparatus and then exposed to extraction in a liquid-solid system
      (solid extraction-SPE) to eliminate redundant pollution, which may interfere with
      compounds by determined analysis. Samples were then analyzed using by capillary
      gas chromatographs "Varian" model 3400 with FID and MS detectors. Results of
      analysis make it possible to determine the influence of industry and traffic on
      atmospheric pollution, to compare results of two analytical methods (GC-FID and
      GC-MS).

PMID- 10943487
TI  - H2O2/UV/air oxidation of organic contaminants in the gas-sparged cyclone reactor.
AB  - In the last decade advanced oxidation processes (AOPs) have been gaining
      importance for destruction of waste as cleaner methods enabling conversion of
      organic contaminants to harmless species. Photodegradation processes in the
      presence of hydrogen peroxide (H2O2), ozone (O3) and titanium dioxide (TiO2) are
      most frequently offered for wastewater treatment. The novel gas-sparged reactor
      equipped with UV lamp proved to be an efficient system for photochemical
      degradation. In this investigation 80 ppm aqueous solution of phenol was treated
      for 40 minutes. 13% of phenol was eliminated in the UV/air system and 73% in the
      UV/H2 O2/air system at 80 l/min air flowrate. Air sparging did not result in
      phenol removal with the gas phase.

PMID- 10943488
TI  - Determination of PAHs and BTEX in air in Zabrze City.

PMID- 10943489
TI  - Application of gel permeation chromatography and HPLC method with fluorescence
      detector to determination of benzo(a)pyrene in food samples.
AB  - During the last three decades contamination of food by traces of toxic substances
      has been the object of intensive research in modern food toxicology. Various
      classes of compounds of different origin were detected in food and beverages. In
      particular nitrosamines and polynuclear aromatic hydrocarbons attracted
      attention, due to their mutagenic and cancerogenic potential (1, 2). Traces of
      PAHs have been detected in many foods, including vegetables, vegetable oils,
      fruits, grains, sea food, grilled and roasted meat, smoked fish, coffee and tea.
      PAHs in food are only a part of the general problem of PAH pollution in the
      environment. The numerous types of PAHs--some 100 have been isolated and
      identified in food and in the environment--are a challenge to modern analytical
      technique. Various chromatographic procedures, including column, paper and thin
      layer chromatography have been applied to isolate these substances from
      contaminated samples. Some of these methods give satisfactory results, especially
      in the determination of single PAHs including benzo(a)pyrene (3). Gas
      chromatography and HPLC are the techniques most widely used to meet these
      analytical demands. Very important are pretreatment of food samples and clean-up
      procedures. In Slovakia limits for B)a)P in food are: 0.001 mg/kg in smoked meat
      and fish products; 0.003 mg/kg in paprika, pepper, sausages. Other PAHs (from US
      EPA 16 PAH) have no limits. This paper describes determination of benzo(a)pyrene
      in different food samples by gel permeation chromatography and the HPLC method
      with a fluorescence detector. State Veterinary Institute (SVU) in Dolny Kubin
      (Slovakia) is authorized for determination of benzo(a)pyrene in all samples,
      which are imported to Slovakia. Many samples with excessive of benzo(a)pyrene
      were from Baltic Sea (especially smoked sprats).

PMID- 10943490
TI  - Biodegradation and genotoxicity of some chemical plant protection products.

PMID- 10943491
TI  - Evaluation of eutrophication of lakes Lielais Baltezers and Mazais Baltezers.

PMID- 10943492
TI  - Ecotoxicological experiences on Lemna minor test system.
AB  - Are plants generally less sensitive to toxicity than aquatic animals as indicated
      by some authors (1)? The use of phytotoxicity (higher plant) tests as a part of
      ecotoxicology is relatively underdeveloped. The objective of this study was to
      compare the results of the OECD Lemna Growth Inhibition Test with other mainly
      used test systems. Three toxicants were tested applying the Alga Growth
      Inhibition Test (Seleneastrum capricornutum), the Daphnia Immobilization Test
      (Daphnia magna) and the MICROTOX-test (Photobacterium phosphoreum). Duckweed
      plants were found to be sensitive to the chemicals tested, with nearly 100%
      inhibition of frond production occurring in the highest concentrations. The
      plants in some samples showed lesions (break up of the colony structure) and loss
      of green pigments (chlorosis), others showed localized dead tissues (necrosis).
      In addition to the morphological deviations (appearance) there is a wide range of
      characteristics to be observed on the test plants: number of fronds, number of
      plants, biomass, dry weight, mortality, CO2 and O2 exchange, concentration of
      chlorophyll a and chlorophyll b. It is consistent that the number of fronds is
      slightly more sensitive than or the same as the number of plants and that the
      biomass tend to be somewhat more tolerant than those for the number of plants
      (2). Applying the simplest way of observation, changes in the frond number were
      recorded. As Lemna minor show a characteristical sensitivity to the different
      kind of chemicals, it is a promising indicator of aquatic toxicity.

PMID- 10943493
TI  - Utilization of microbiotests to assess the contamination of water-bases.
AB  - In the present study 4 hazardous wastes originated from 4 different typical
      industrial activities (leachates of waste oil, waste stockpiles of aluminium
      factory, sewage of leather industry and of the chemical industry) were examined
      with several Toxkit microbiotests: the Algaltoxkit, the Protoxkit, the Daphtoxkit
      and the Thamnotoxkit. The data obtained with the microbiotests were compared to
      those obtained with the standard conventional acute toxicity tests. The goal of
      the study was to try out the reproducibility of the tests on the same samples,
      prepared in the same laboratory and provided to all the participants of the
      interlaboratory exercise. The first reproducibility evaluation of the tests was
      made with the reference toxicant potassium dichromate (K2Cr2O7). The outcome was
      that the lowest coefficients of variation were found at the Thamnotoxkit and
      highest with Algaltoxkit. The same findings were observed with the industrial
      waste samples. Different responses were obtained depending on the preparation and
      the character of the waste. For example, whereas a strong (and highest) toxic
      effect was found with the Thamnotoxkit, the algal cells in the Algaltoxkit test
      grew better than in the controls, when exposed to the same waste sample. The
      sensitivity of the Protoxkit ciliates was the lowest for all the wastes examined.
      In conclusion of this study, the experience gained and data obtained indicate
      that the Toxkit microbiotests are suited for routine monitoring after
      modification of some technical aspects.

PMID- 10943494
TI  - The effect of the combined liquid artificial fertilizer on the embryogenesis of
      birds.

PMID- 10943495
TI  - An algorithmic approach to evaluation of the flatfoot. Avoidance of pitfalls.
AB  - The authors have attempted to lead the reader through a comprehensive and
      systematic diagnosis of the patient with the flatfoot. The authors followed the
      familiar SOAP format. Within each of the major steps (subjective findings,
      objective findings, assessment, and plan) a systematic algorithm is proposed.
      These are designed with the objective of comprehensively evaluating the patient.
      This should dissuade the reader from myopically approaching the flatfoot, and
      potentially missing comorbid or etiologic systemic disease. A brief introduction
      to a systematic treatment philosophy is also presented. Unfortunately exhaustive
      discussion of each of the steps would require a separate article. The authors
      hope that the controversies highlighted will stimulate further research into this
      subject. It is also hoped that anyone approaching the patient with flexible
      flatfoot would avoid some of the dogmatic philosophies that have plagued this
      subject. Until well-developed scientific research answering the basic questions
      is done, all currently available approaches are based on opinion and personal
      bias.

PMID- 10943496
TI  - Risk factors that may adversely modify the natural history of the pediatric
      pronated foot.
AB  - Flatfoot is one of the most common conditions seen in pediatric podiatry
      practice. There is no universally accepted definition for flatfoot. Flatfoot is a
      term used to describe a recognizable clinical deformity created by malalignment
      at several adjacent joints. Clinically, a flatfoot is one that has a low or
      absent longitudinal arch. Determining flexibility (physiologic) or rigidity
      (pathologic) is the first step in management. A flexible flat foot will have an
      arch that is present in open kinetic chain (off weight-bearing) and lost in
      closed kinetic chain (weight-bearing). A rigid flatfoot has loss of the
      longitudinal arch height in open and closed kinetic chain. According to Mosca,
      "The anatomic characteristics of a flatfoot are excessive eversion of the
      subtalar complex during weight-bearing with plantarflexion of the talus,
      plantarflexion of the calcaneus in relation to the tibia, a dorsiflexed and
      abducted navicular and a supinated forefoot." Normally developing infants have a
      flexible flatfoot and gradually develop a normal arch during the first decade of
      life. When evaluating an infant for a pronated condition, the examiner must also
      consider other risk factors that may affect the foot in its overall development.
      These contributing factors will play a role in the development of a treatment
      plan. The risk factors include ligamentous laxity, obesity, rotational
      deformities, tibial influence, pathological tibia varum, equinus, presence of an
      os tibiale externum, and tarsal coalitions. The authors realize other less
      significant factors exist but are not as detrimental to the foot as the primary
      ones discussed in depth. The primary risk factors that affect the pronated foot
      have been outlined. The clinician should always examine for these conditions when
      presented with a child exhibiting pronatory changes. A thorough explanation to
      the parents as to the consequential effects of these risk factors and their
      effects on the pediatric pronated foot is paramount to providing an acceptable
      comprehensive treatment program. Children often are noncompliant with such
      treatments as stretching and orthotic maintenance. The support of the parents is
      crucial to maintaining an effective treatment program continued at home.

PMID- 10943497
TI  - The oblique talus deformity. What is it, and what is its clinical significance in
      the scheme of pronatory deformities?
AB  - The advantage for maintaining oblique talus deformity as a diagnostic entity is
      obvious. It describes a deformity that is somewhere between the severe form of
      flexible pes planus and congenital convex pes valgus. It is important to
      recognize that the two subsets (oblique talus deformity with maintenance of the
      calcaneal inclination angle and oblique talus deformity with reversal of the
      calcaneal inclination) differ from congenital convex pes valgus by the absence of
      dislocation of the talonavicular joint. In many cases, the talonavicular joint is
      merely pushed to its maximum range, and does not even meet the definition of
      subluxation. Maintaining these distinctions prevents overdiagnosis of congenital
      convex pes valgus. Additionally, better evaluation of treatment for congenital
      convex pes valgus results because those cases with better prognosis and better
      response to nonsurgical intervention are not included in the data for the
      management of congenital convex pes valgus.

PMID- 10943498
TI  - Subtalar arthroereisis in the neurologically normal child.
AB  - The problem of hypermobile or flexible flatfoot in children has been well
      documented in the medical literature for many years, and refers to a foot that
      has excessive motion in the form of pronation at the subtalar joint. The clinical
      presentation of a hypermobile flatfoot can be observed in all three planes. The
      use of arthroereisis to treat hypermobile flatfoot has been shown to effect the
      foot in all three planes; however, the most significant clinical improvement
      usually is seen in the frontal plane where a dramatic reduction of calcaneovalgus
      is often apparent. The authors provide figures and procedure for the surgical
      insertion of the subtalar arthroereisis (STA) peg.

PMID- 10943500
TI  - Congenital vertical talus.
AB  - The author provides a description of the deformity congenital vertical talus,
      including characteristics and contributing factors. Also outlined are the
      incidence, cause, and pathogenesis; radiographic features; anatomy; and treatment
      of the condition. The author includes results and discussion of surgical
      treatment.

PMID- 10943499
TI  - Sta-Peg arthroereisis for treatment of the planovalgus foot in cerebral palsy.
AB  - The Sta-Peg procedure is most effective in the non-rigid foot in which reasonable
      muscle balance can be attained. Where such balance cannot be attained or where
      rigid deformity exists, this procedure will not solve the problem and should not
      be used. The authors want to emphasize that this study pertains to the use of Sta
      Peg in the valgus foot caused by cerebral palsy. The procedure is rarely needed
      in the flexible flatfoot of a normal child.

PMID- 10943501
TI  - Pronation. The orthotist's view.
AB  - Pronation of the foot is one of the commonest reasons for prescribing orthotics
      for the lower extremity. Many different bracing systems are available for the
      management of this complex problem. To select the most efficient method for a
      given case, the healthcare professional and the orthotist must have a firm
      understanding of the pathophysiology of pronation and the special requirements of
      each patient. Additionally, the medical condition resulting in pronation and
      necessitating bracing may alter after the selection of the orthoses. Selection of
      cases for treatment depends on the type, because pronatory deformities can be
      grouped according to markers that are cause specific. The use of orthotic therapy
      as a modifier of the natural history in simple pronation remains controversial.

PMID- 10943502
TI  - Flatfoot deformity pathogenesis. A trilogy.
AB  - The significant conclusion from this trilogy is that most developmental flatfeet
      are present at birth. It is likely that intrauterine forces and fetal foot
      position initially create the abnormal bony relationships between anatomically
      normal bones. This bony relationship is present before the child takes his first
      step. Second, as the result of this abnormal relationship between normal bones,
      the active muscular force balance between opposing muscle groups is distorted.
      This allows one muscle to have a mechanical advantage over its antagonist. This
      actively maintains and progressively worsens the abnormal bony relationship.
      Third, this abnormal bony relationship and disturbed muscular mechanical
      advantage exert their influence immediately at the point of heel contact in the
      gait cycle. At this point, the foot and posterior talocalcaneal joint are
      dorsiflexed relative to the supporting surface so that the majority of motion
      occurs in the transverse body plane. Finally, the goal of an orthotic device is
      to simply give the disadvantaged (muscularly challenged) muscle groups more time
      in the gait cycle to re-establish the normal bony relationships. The orthotic
      will restore the foot to a stable sturdy foundation acting as an effective lever
      mechanism that can propel the body forward efficiently in gait. Much of the
      author's previous discussion is a natural progression of ideas that originated
      during training with the late James V. Ganley, DPM. He was a proponent of the
      philosophy that the talus was blamed for causing a flatfoot deformity. Ganley
      felt that the talus was relatively innocent in the cause of this condition and
      the remainder of the bones of the foot were the true villains in the pathogenesis
      of the valgus foot. However, Ganley regarded the abnormal bone relationships of
      the deformity as if they are passive in nature. This article places emphasis on
      how the active muscular forces create the abnormal bony relationships.

PMID- 10943504
TI  - The rigid flatfoot. Tarsal coalitions.
AB  - Tarsal coalitions are the major cause of painful rigid flatfoot deformity in
      children and adolescents. Talocalcaneal and calcaneonavicular coalitions are the
      most common sites. They are often bilateral and may be asymptomatic. They
      represent a failure of fetal mesenchymal differentiation, and onset of symptoms
      in children often corresponds to the time of ossification of the fibrous or
      cartilaginous coalition. The most common presenting symptom is pain, and
      diagnosis is aided by plain radiographs and computerized tomography. Some
      patients respond to conservative measures, but surgical treatment is often
      required. Resection and interposition of fat or tendon (talocalcaneal) or muscle
      (calcaneonavicular) are the most common operative treatments, with arthrodesis
      reserved for symptomatic recurrences, patients with degenerative changes, and
      those with multiple coalitions.

PMID- 10943505
TI  - The biology of Cryptosporidium.

PMID- 10943506
TI  - Laboratory diagnosis of Cryptosporidium parvum infection.

PMID- 10943503
TI  - Surgical treatment of the child's and adolescent's flexible flatfoot.
AB  - Operative intervention for juvenile flexible flatfoot is considered after a
      protracted course of orthotics and shoe modifications have failed to relieve
      associated symptoms. Surgical treatment options include hindfoot fusion, soft
      tissue procedures, calcaneal osteotomies, limited midtarsal arthrodeses,
      combination techniques, and subtalar arthroereisis. Long-term, high success rates
      have been documented with use of combination procedures and the anterior
      calcaneal osteotomy of Evans.

PMID- 10943507
TI  - Clinical aspects of human cryptosporidiosis.

PMID- 10943508
TI  - Host immune responses against Cryptosporidium.

PMID- 10943509
TI  - Gene discovery in Cryptosporidium parvum: expressed sequence tags and genome
      survey sequences.

PMID- 10943511
TI  - Biology of microsporidia.

PMID- 10943510
TI  - Epidemiology and strain variation of Cryptosporidium parvum.

PMID- 10943512
TI  - Diagnosis and clinical aspects of human microsporidiosis.

PMID- 10943513
TI  - Immunology of microsporidiosis.

PMID- 10943514
TI  - Molecular phylogeny and diagnostic approaches to microsporidia.
AB  - Knowledge about the phylum Microspora and its relationship to humans is in a
      period of rapid growth as noninvasive diagnostic techniques for microsporidia
      have been developed and are being applied to both clinical and epidemiologic
      studies. As these techniques have improved, new microsporidian pathogens and
      reservoir hosts of the microsporidia infecting humans are being identified.
      Recent phylogenetic data suggest that microsporidia are related to the fungi.
      This information may prove useful in investigations into new therapeutic
      strategies for these emerging human pathogens.

PMID- 10943515
TI  - Epidemiology and zoonotic aspects of microsporidia of mammals and birds.

PMID- 10943516
TI  - Lipid formulations of amphotericin B.
AB  - The incidence of systemic fungal infections, especially in immunocompromised
      patients, has continued to increase during the past few decades. Treatment with
      conventional amphotericin B has been the standard care for the majority of
      patients with invasive fungal infections, despite its associated toxicity. Three
      lipid formulations of amphotericin B have now been approved for use in the United
      States. The pharmacology, pharmacokinetics, clinical experience, toxicity, dosing
      strategies, and cost of these three preparations--amphotericin B lipid complex,
      amphotericin B colloidal dispersion, and liposomal amphotericin B--were reviewed
      in detail in this chapter. The clinical data indicate that lipid formulations of
      amphotericin B represent an important therapeutic modality in the management of
      invasive fungal infections.

PMID- 10943517
TI  - Cost-effectiveness in the use of antibiotics.

PMID- 10943518
TI  - Topical antibacterial agents: role in prophylaxis and treatment of bacterial
      infections.

PMID- 10943519
TI  - The fluoroquinolones after ciprofloxacin and ofloxacin.

PMID- 10943520
TI  - Trends in treatment of antimicrobial-resistant enterococcal infections.

PMID- 10943521
TI  - Update on culture-negative endocarditis.

PMID- 10943522
TI  - Non-typhoid Salmonella: a review.

PMID- 10943523
TI  - Acute bronchitis in the healthy adult.

PMID- 10943524
TI  - Management of otitis media with antimicrobial agents.

PMID- 10943525
TI  - The child with congenital toxoplasmosis.

PMID- 10943526
TI  - A current approach to the management of tuberculosis infection.

PMID- 10943527
TI  - Respiratory syncytial virus infections in immunocompromised adults.
AB  - The past decade has witnessed a growing appreciation of the existence, frequency,
      and potential lethality of community respiratory virus infections such as RSV in
      some subsets of immunocompromised adults. The enigmatic "idiopathic pneumonia"
      and "pneumonia of unknown origin" have become more fathomable. As a result, a
      simple upper respiratory illness in a high-risk immunocompromised adult is no
      longer viewed as trivial. The paramount importance of simple hygienic practices
      has been underscored, and contamination of high-risk immunocompromised patients
      with respiratory secretions is now discouraged with the same rigor as
      contamination with urine, feces, or blood. Likewise, the risks and benefits of
      administering intensive chemotherapy in the setting of a seemingly benign upper
      respiratory illness are now weighed heavily. The diagnosis is suspected and
      pursued, and the available therapies are administered promptly. Widespread
      efforts are now under way to elucidate the pathogenesis of these viral pneumonias
      and to identify the immunodeficiencies predisposing patients to serious disease.
      In addition, efforts are being made to develop effective diagnostic,
      prophylactic, and therapeutic strategies. The growing need for more effective,
      easier-to-administer, less costly antiviral therapy is apparent.

PMID- 10943528
TI  - Infections of long intravenous lines: new developments and controversies.

PMID- 10943530
TI  - Herpes simplex of the ocular anterior segment.

PMID- 10943529
TI  - Endophthalmitis.

PMID- 10943531
TI  - Update on chronic granulomatous disease: the concept of the near-normal host.

PMID- 10943532
TI  - Anthrax: clinical features, pathogenesis, and potential biological warfare
      threat.

PMID- 10943533
TI  - Inpatient dermatology. The difficulties, the reality, and the future.
AB  - Changes in the health care delivery system have profoundly affected medical
      dermatology in the United States. Although a significant number of patients are
      still being admitted for skin and skin-related disorders, only a minority are now
      admitted by dermatologists. An analysis of the mechanics of such a change and a
      national perspective is presented.

PMID- 10943534
TI  - The effect of health care delivery systems on admission to and treatment at an
      inpatient dermatology unit.
AB  - The University of Miami Department of Dermatology has maintained an active
      inpatient unit. Analysis of data from a 12 month period from 1995-1996 showed 562
      admissions. Cutaneous lymphoma, psoriasis, and chronic wounds accounted for over
      half the admissions. Most patients were insured by a fee-for-service system, and
      compared to patients insured by managed care systems or patients who were
      indigent, fee-for-service patients had the shortest length of stay. Using a case
      mix severity index, indigent patients had the greatest disease severity followed
      by fee-for-service patients. Patients enrolled in managed care systems had the
      least severity suggesting that factors other than disease severity alone may play
      a role in determining why patients are admitted.

PMID- 10943535
TI  - Inpatient dermatology. United Kingdom and United States similarities: moving with
      the times or being relegated to the back bench?
AB  - Financial and managerial pressures have resulted in the rationalization of
      inpatient dermatology beds in the United Kingdom. Although these two countries
      have different populations and health care systems, both have been subject to
      similar drives toward cost containment. Advances in dermatology have broadened
      the reach of outpatient-based dermatological care that provides for most skin
      patients; however, inpatient treatment remains an important and essential
      therapeutic option for a group of patients. Dermatologic inpatient care may be
      inadequately and inefficiently provided by nondermatologists. It is important to
      ensure that the quality of dermatology inpatient services is maintained at the
      highest standard while using, and working within, a constantly evolving system of
      health care. Only then can dermatologists tailor the specialty to maximize the
      benefits for the patients and the profession as a whole.

PMID- 10943536
TI  - Erythroderma.
AB  - Erythroderma can be caused by a variety of underlying dermatoses, infections, and
      systemic diseases. Many of the findings on history, physical examination, and
      laboratory evaluation are nondiagnostic. Distinctive clinical and laboratory
      features pointing to a specific disease may be evident, however. Conclusive
      clinicopathologic correlation may require multiple and repeated skin biopsies.
      The prognosis of erythroderma has improved with the advent of innovative
      dermatologic therapies (e.g., cyclosporine and synthetic retinoids) and advances
      in the management of systemic manifestations. Death from sepsis, cardiac failure,
      adult respiratory distress syndrome, and capillary leak syndrome continue to be
      rarely reported. A high index of suspicion for these complications must be
      maintained to facilitate early medical intervention.

PMID- 10943537
TI  - Cutaneous T-cell lymphoma and cutaneous graft-versus-host disease. Two
      indications for photopheresis in dermatology.
AB  - Dermatologists are frequently involved in the management of cutaneous T-cell
      lymphoma (CTCL) and graft-versus-host disease (GVHD). The similarities of these
      two entities are reviewed in the context of clinical and histologic findings,
      pathogenesis, and therapy. Photopheresis therapy (extracorporeal
      photochemotherapy) is used in the treatment of both entities, and the mechanisms
      underlying the responses represent yet another striking similarity of these two
      crippling dermatologic diseases.

PMID- 10943538
TI  - Treatment of patients hospitalized for psoriasis.
AB  - Life quality of patients with severe forms of psoriasis can be greatly improved
      with an appropriate inpatient therapy. In an effort to better understand how to
      treat this disorder, this article explores several aspects of inpatient treatment
      for severe psoriasis. Special attention is given to the Goeckerman regimen,
      combination therapies, and some innovative approaches that may shorten the
      hospital stay and prolong the remission periods of the disease.

PMID- 10943539
TI  - Pulse glucocorticoids.
AB  - High-dose intravenous (i.v.) methylprednisolone has been used therapeutically in
      a number of medical fields to avoid the complications and side effects of long
      term glucocorticoid (GC) therapy and because of the perception that high-dose
      i.v. methylprednisolone may have "special" therapeutic effects. It is possible
      that aggressive early therapy with GCs allows for a more rapid taper of GCs and
      therefore prevents some of the dose-related side effects associated with long
      term use. Some of the neurologic and rheumatologic literature related to multiple
      sclerosis and lupus nephritis suggest that i.v. methylprednisolone has
      therapeutic effects that are different from those of conventional doses of oral
      prednisone. There is still considerable debate about this in nondermatologic
      fields, and extrapolation of the role of pulse i.v. methylprednisolone to
      dermatologic disease, where trials are lacking, is difficult. Given this subset
      of possible candidates of this therapy as suggested by anecdotal reports, there
      is at least a rationale for considering the use of this modality in a subset of
      patients.

PMID- 10943540
TI  - Intravenous immunoglobulin in autoimmune and inflammatory dermatoses. A review of
      proposed mechanisms of action and therapeutic applications.
AB  - Off-label use of intravenous immunoglobulin (IVIG) at high doses has resulted in
      numerous anecdotal reports of its effectiveness in a variety of autoimmune and
      inflammatory conditions. Despite its growing acceptance as a viable therapeutic
      option in the management of several such disorders, the poorly defined mechanism
      of action of IVIG has stifled its rational therapeutic application. The lack of
      carefully designed prospective randomized clinical trials has further fueled
      controversy and mitigates against optimal application of this burgeoning therapy.
      Nevertheless, some standardization of IVIG therapy is slowly advancing that
      promises to support the use of this treatment for a growing number of autoimmune
      and inflammatory dermatoses.

PMID- 10943541
TI  - Pulse intravenous cyclophosphamide therapy for dermatologic disorders.
AB  - Cyclophosphamide is a potent immunosuppressive agent that has an important role
      in the treatment of autoimmune, neoplastic, granulomatous, and neutrophilic
      disorders. Pulse intravenous cyclophosphamide has been shown to be efficacious
      for several dermatologic disorders, particularly pemphigus vulgaris, with a low
      incidence of toxicity reported. As reported earlier, studies performed on the use
      of pulse intravenous cyclophosphamide in the treatment of a variety of
      dermatology-related diseases strongly suggest that the toxicities frequently
      noted with the use of oral cyclophosphamide therapy may be significantly less
      common with pulse intravenous administration of cyclophosphamide. The short
      follow-up period of patients treated with this modality so far, however, requires
      constant vigilance for the development of side effects, particularly secondary
      malignancy. At this time, pulse intravenous cyclophosphamide is a promising
      treatment modality with an acceptable risk profile for moderate-to-severe
      dermatologic diseases recalcitrant to standard therapy. Prospective comparative
      trials are needed to assess further the efficacy and toxicity of this therapy.

PMID- 10943542
TI  - Other novel immunosuppressants.
AB  - The use of immunosuppressive agents in dermatology has increased widely. The role
      of these medications has become increasingly important for the treatment of
      dermatologic disorders in an inpatient setting, where there is frequently a
      requirement for highly potent, fast-acting, effective agents. This article
      presents an overview of the general application, mechanisms of action,
      metabolism, and adverse effects commonly associated with systemic
      immunosuppressive agents used in dermatology.

PMID- 10943543
TI  - Toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is a rare but life-threatening adverse drug
      reaction. Implicated drugs are sulfonamides, anticonvulsants, allopurinol, and
      pyrazolone derivatives. Recently, advances in pathogenesis have been made in two
      directions. It is now known that (1) most patients with TEN have an abnormal
      metabolism to the culprit drug; and (2) the mechanism leading to epidermal
      necrolysis seems to be a cell-mediated cytotoxic reaction. The treatment remains
      symptomatic.

PMID- 10943544
TI  - Cutaneous (non-HIV) infections.
AB  - Cutaneous infections continue to represent a large proportion of inpatient
      dermatology. Though most infectious skin diseases do not warrant hospitalization,
      some do and can rapidly become fatal if not treated promptly. A selected group of
      infections are reviewed--primary cutaneous infections, exotoxin-mediated
      syndromes, and systemic infections--that warrant hospitalization. Dermatologists
      play a critical role in the synthesis of patient history and appreciation of
      morphologic skin disease, which, when coupled with appropriate lab tests, may
      help to establish a diagnosis allowing for the timely implementation of effective
      and targeted therapy.

PMID- 10943545
TI  - HIV and AIDS in inpatient dermatology. Approach to the consultation.
AB  - In the inpatient setting, the dermatologic consultant is called on to address the
      whole spectrum of cutaneous disease seen in HIV/AIDS patients, with severity
      varying from severe life-threatening to less serious conditions that dramatically
      affect quality of life. Rather than reviewing a "laundry list" of conditions
      associated with HIV/AIDS or the most severe conditions, this article aims to
      demonstrate a systematic approach to inpatient dermatology consultation in
      HIV/AIDS patients and to briefly review several common and interesting topics
      frequently addressed in the inpatient setting (e.g., medications issues, and
      phototherapy in HIV-infected patients).

PMID- 10943546
TI  - Skin grafting.
AB  - No longer an option of last resort, skin grafting has become a technique that is
      routinely and sometimes preferentially considered as skin replacement for burns,
      chronic ulcers, and skin defects after cutaneous surgical procedures. When
      selected as the best alternative for wound closure, autologous skin grafts are
      commonly considered the gold standard. Availability of autologous grafts is a
      major obstacle, however, and the search for a manufactured skin replacement has
      continued. In cases in which autologous grafts cannot be performed, skin
      substitutes have become an attractive alternative.

PMID- 10943547
TI  - Inpatient dermatology consultation.
AB  - Common dermatologic conditions and skin signs of systemic disease are routinely
      present in hospitalized patients. Rapid detection and identification of these
      changes can have a significant impact on the patient's hospital course. Inpatient
      dermatology consultation can improve diagnostic accuracy, efficiency, and
      treatment of hospitalized patients with cutaneous findings. This article
      discusses the clinical aspects of inpatient dermatology consultation and the
      features of effective consultation.

PMID- 10943548
TI  - Recognition and management of unusual cutaneous tumors.
AB  - This article has briefly outlined some of the more unusual cutaneous neoplasms
      that may be encountered in a dermatologic practice. Although rare, they must
      always be kept in mind and included in the differential diagnosis. Because of the
      highly aggressive nature of many of these tumors, delay in diagnosis and
      treatment could be fatal. A high level of suspicion is necessary for the correct
      prebiopsy diagnosis.

PMID- 10943549
TI  - Cold-shock response and adaptation.

PMID- 10943550
TI  - Cold shock response in Escherichia coli.
AB  - Sensing a sudden change of the growth temperature, all living organisms produce
      heat shock proteins or cold shock proteins to adapt to a given temperature. In a
      heat shock response, the heat shock sigma factor plays a major role in the
      induction of heat shock proteins including molecular chaperones and proteases,
      which are well-conserved from bacteria to human. In contrast, no such a sigma
      factor has been identified for the cold shock response. Instead, RNAs and RNA
      binding proteins play a major role in cold shock response. This review describes
      what happens in the cell upon cold shock, how E. coli responds to cold shock, how
      the expression of cold shock proteins is regulated, and what their functions are.

PMID- 10943551
TI  - Cold shock response in Bacillus subtilis.
AB  - Following a rapid decrease in temperature, the physiology of Bacillus subtilis
      cells changes profoundly. Cold shock adaptation has been monitored at the level
      of membrane composition, adjustment in DNA topology, and change in cytosolic
      protein synthesis/composition. Some major players in these processes (cold-stress
      induced proteins and cold acclimatization proteins, CIPs and CAPs) have been
      identified and mechanisms in cold shock acclimatization begin to emerge; however,
      important questions regarding their cellular function still need to be answered.

PMID- 10943552
TI  - Cold shock response and low temperature adaptation in psychrotrophic bacteria.
AB  - Psychrotrophic bacteria are capable of developing over a wide temperature range
      and they can grow at temperatures close to or below freezing. This ability
      requires specific adaptative strategies in order to maintain membrane fluidity,
      the continuance of their metabolic activities, and protein synthesis at low
      temperature. A cold-shock response has been described in several psychrotrophic
      bacteria, which is somewhat different from that in mesophilic microorganisms: (i)
      the synthesis of housekeeping proteins is not repressed following temperature
      downshift and they are similarly expressed at optimal and low temperatures (ii)
      cold-shock proteins or Csps are synthesized, the number of which increases with
      the severity of the shock (iii) a second group of cold-induced proteins, i.e. the
      cold acclimation proteins or Caps, comparable with Csps are continuously
      synthesized during prolonged growth at low temperature. Homologues to CspA, the
      major cold-shock protein in E. coli, have been described in various
      psychrotrophs, but unlike their mesophilic counterparts, they belong to the group
      of Caps. Although they have been poorly studied, Caps are of particular
      importance since they differentiate psychrotrophs from mesophiles, and they are
      probably one of the key determinant that allow life at very low temperature.

PMID- 10943553
TI  - Responses to cold shock in cyanobacteria.
AB  - Acclimation of cyanobacteria to low temperatures involves induction of the
      expression of several families of genes. Fatty acid desaturases are responsible
      for maintaining the appropriate fluidity of membranes under stress conditions.
      RNA-binding proteins, which presumably act analogously to members of the
      bacterial Csp family of RNA chaperones, are involved in the maintenance of the
      translation under cold stress. The RNA helicase, whose expression is induced
      specifically by cold, might be responsible for modifying inappropriate secondary
      structures of RNAs induced by cold. The cold-inducible family of CIp proteins
      appears to be involved in the proper folding and processing of proteins. Although
      genes for cold-inducible proteins in cyanobacteria are heterogeneous, some common
      features of their untranslated regulatory regions suggest the existence of a
      common factor(s) that might participate in regulation of the expression of these
      genes under cold-stress conditions. Studies of the patterns of expression of cold
      inducible genes in cyanobacteria have revealed the presence of a cold-sensing
      mechanism that is associated with their membrane lipids. Available information
      about cold-shock responses in cyanobacteria and molecular mechanisms of cold
      acclimation are reviewed in this article.

PMID- 10943554
TI  - Molecular responses of plants to cold shock and cold acclimation.
AB  - The Plant Kingdom encompasses a grouping of mostly sessile organisms that show
      extreme variation in morphology, size, ecological adaptation, life cycle, and
      climatic tolerance. With the exception of low elevation tropical environments,
      plants living just about anywhere else in the world may be subject to
      temperatures below that which are optimal for growth and survival. Consequently,
      the range of tolerance to low temperature stress in the Plant Kingdom is as great
      as the natural variation in low temperatures. For mesophilic plants, sub-optimal
      low temperature could range from 15 degrees C down to -55 degrees C. In the past
      10 years, more than 100 genes have been shown to be preferentially expressed in
      response to low temperatures. Significant progress in understanding the responses
      of plants to low temperature has occurred in the areas of signal perception and
      transduction pathways, transcriptional control and the characterization of a
      variety of stress-related proteins. A common aim of much of the research on cold
      stress in plants is to find ways to enhance the stress tolerance and reduce
      economic losses.

PMID- 10943555
TI  - Cold shock response in mammalian cells.
AB  - Compared to bacteria and plants, the cold shock response has attracted little
      attention in mammals except in some areas such as adaptive thermogenesis, cold
      tolerance, storage of cells and organs, and recently, treatment of brain damage
      and protein production. At the cellular level, some responses of mammalian cells
      are similar to microorganisms; cold stress changes the lipid composition of
      cellular membranes, and suppresses the rate of protein synthesis and cell
      proliferation. Although previous studies have mostly dealt with temperatures
      below 20 degrees C, mild hypothermia (32 degrees C) can change the cell's
      response to subsequent stresses as exemplified by APG-1, a member of the HSP110
      family. Furthermore, 32 degrees C induces expression of CIRP (cold-inducible RNA
      binding protein), the first cold shock protein identified in mammalian cells,
      without recovery at 37 degrees C. Remniscent of HSP, CIRP is also expressed at 37
      degrees C and developmentary regulated, possibly working as an RNA chaperone.
      Mammalian cells are metabolically active at 32 degrees C, and cells may survive
      and respond to stresses with different strategies from those at 37 degrees C.
      Cellular and molecular biology of mammalian cells at 32 degrees C is a new area
      expected to have considerable implications for medical sciences and possibly
      biotechnology.

PMID- 10943556
TI  - The major facilitator superfamily.
AB  - In 1998 we updated earlier descriptions of the largest family of secondary
      transport carriers found in living organisms, the major facilitator superfamily
      (MFS). Seventeen families of transport proteins were shown to comprise this
      superfamily. We here report expansion of the MFS to include 29 established
      families as well as five probable families. Structural, functional, and
      mechanistic features of the constituent permeases are described, and each newly
      identified family is shown to exhibit specificity for a single class of
      substrates. Phylogenetic analyses define the evolutionary relationships of the
      members of each family to each other, and multiple alignments allow definition of
      family-specific signature sequences as well as all well-conserved sequence
      motifs. The work described serves to update previous publications and allows
      extrapolation of structural, functional and mechanistic information obtained with
      any one member of the superfamily to other members with limitations determined by
      the degrees of sequence divergence.

PMID- 10943557
TI  - Modular assembly of voltage-gated channel proteins: a sequence analysis and
      phylogenetic study.
AB  - Voltage-sensitive cation-selective ion channels of the voltage-gated ion channel
      (VGC) superfamily were examined by a combination of sequence alignment and
      phylogenetic tree construction procedures. Segments of the alpha-subunits of K+
      selective channels homologous to the structurally elucidated KcsA channel of
      Streptomyces lividans were multiply aligned, and this alignment provided the
      database for computer-assisted structural analyses and phylogenetic tree
      construction. Similar analyses were conducted with the four homologous repeats of
      the alpha-subunits from representative Ca2+- and Na+-selective channels, as well
      as with the ensemble of K+, Ca2+ and Na+ channels. In both the single subunit of
      the K+ channels and the individual repeats of the Ca2+ and Na+ channels, the
      analyses suggest the occurrence of at least two tandemly arranged modules
      corresponding to the predicted voltage-sensor domain and the pore domain. The
      phylogenetic analyses reveal strict clustering of segments according to cation
      selectivity and repeat unit. We surmise that the pore module of the prokaryotic
      K+ channel was the primordial polypeptide upon which other modules were
      superimposed during evolution in order to generate phenotypic diversity. These
      observations may prove applicable to all members of the VGC family yet to be
      discovered throughout the prokaryotic and eukaryotic kingdoms.

PMID- 10943558
TI  - Novel phosphotransferase systems revealed by bacterial genome analysis: the
      complete repertoire of pts genes in Pseudomonas aeruginosa.
AB  - We herein describe all genes encoding constituents of the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS) in the 6Mbp genome of
      the opportunistic human pathogen, Pseudomonas aeruginosa. Only four gene clusters
      were found to encode identifiable PTS homologues. These genes clusters encode
      novel multidomain proteins, two complete sugar-specific PTS phosphoryl transfer
      chains for the metabolism of fructose and N-acetylglucosamine, and a complex
      regulatory system that may function to coordinate carbon and nitrogen metabolism.
      No previously characterized organism has been shown to exhibit such a novel and
      restricted complement of PTS proteins.

PMID- 10943559
TI  - Occurrence of mazEF-like antitoxin/toxin systems in bacteria.
AB  - The mazEF locus of Escherichia coil located in an operon together with the
      upstream relA gene (encoding ATP:GTP 3'-pyrophosphotransferase; (p)ppGpp
      synthetase), encodes an antitoxin/toxin system which might play a role in
      programmed cell death under stress and starvation conditions at high cell
      densities. By homology searches, chromosomally encoded orthologous systems were
      identified in a variety of bacteria, sometimes without the MazE-like antitoxin,
      and several bacterial species possess multiple MazEF-like systems (paralogs). In
      many gram positive bacteria, the mazEF-locus is located directly upstream of the
      sigB (stress sigma factor sigmaB) operon in a putative operon together with the
      upstream dal (aIr) gene (encoding D-alanine racemase). The acidic antitoxins are
      less conserved than the basic toxins. The differences in genomic organization of
      the mazEFloci in E. coli versus those in gram positive bacteria might indicate
      their association with different stress response regulons in these organisms. A
      study on the sigmaB operon of Staphylococcus aureus showed that the mazF gene of
      this organism is cotranscribed with the sigmaB operon in response to heat shock,
      providing the first example that the expression of the mazEFlocus might be indeed
      associated with stress responses.

PMID- 10943560
TI  - A specialized version of the HD hydrolase domain implicated in signal
      transduction.

PMID- 10943561
TI  - Life with no sugars?

PMID- 10943562
TI  - A reporter gene assay for inhibitors of the bacterial phosphoenolpyruvate: sugar
      phosphotransferase system.
AB  - The phosphoenolpyruvate:sugar phosphotransferase system (PTS) plays a key role in
      sugar uptake and metabolic regulation in bacteria. PTS proteins form a divergent
      phosphorylation cascade. Enzyme I (EI) is at the top of the cascade and mediates
      phosphoryl-transfer from phosphoenolpyruvate to the phosphoryl-carrier protein
      HPr, which then distributes the phosphoryl-groups to the different carbohydrate
      transporters. In addition, some PTS proteins have a regulatory function in
      catabolite repression, inducer exclusion and chemotaxis which is modulated by
      their degree of phosphorylation in response to the availability of substrates.
      Using as a reporter the IacZ gene under control of the bgl t2 transcriptional
      terminator and as an effector the transcriptional antiterminator LicT from B.
      subtilis, a two-plasmid reporter gene system was constructed in order to monitor
      PTS activity. LicT, when present at low concentration in E. coli, is inactivated
      by EI/HPr-dependent phosphorylation and conversely is active in a ptsl- mutant
      lacking El. Active LicT allows for transcriptional readthrough at bgl t2,
      resulting in a full-length lacZ transcript. Beta-galactosidase activities are
      increased 4-8-fold in a ptsl+ strain growing on PTS substrates relative to growth
      on non-PTS substrates and approximately 30-fold in a ptsl- mutant. This gain-of
      function in response to dephosphorylation of El or lack of active El can be used
      to monitor changes of El activity caused by mutations and environmental factors
      and for screening and validation of inhibitors of the PTS as potentially novel
      antibacterial compounds.

PMID- 10943563
TI  - Epitope tagging analysis of the outer membrane folding of the molecular usher
      FaeD involved in K88 fimbriae biosynthesis in Escherichia coli.
AB  - To analyse the outer membrane folding of the molecular usher FaeD, tagged
      derivatives were prepared and their expression, tag-localisation and functioning
      in K88 fimbriae biosynthesis was studied. A semi-random insertion mutagenesis
      approach with factor Xa cleavage sites yielded six tagged FaeD derivatives. A
      site-directed mutagenesis approach in which c-myc epitopes were inserted yielded
      twenty-one different derivatives. Four tagged FaeD constructs were not expressed
      in the outer membrane as full-sized proteins to levels that could be detected by
      using immunoblotting analyses. Two of these had an insertion in the amino
      terminal part of FaeD, whereas the other two had a tag inserted in the carboxyl
      terminal part. The latter ones yielded stable carboxyl-terminally shortened
      truncates of about 70 kDa, as did other mutations in this region. Six tagged
      derivatives were expressed but the location of the tag with respect to the outer
      membrane could not be determined, possibly due to shielding. Functional analysis
      showed that insertion of a tag in two regions of FaeD, a central region of
      approximately 200 amino acid residues (a.a. 200-400) and the carboxyl-terminal
      region (a.a. 600-end), resulted in a defective K88 fimbriae biosynthesis. In
      frame deletions in the amino-terminal region of FaeD abolished fimbriae
      production. The integrity of these regions is obviously essential for fimbriae
      biosynthesis. Based on the results and with the aid of a computer analysis
      programme for the prediction of outer membrane beta-strands, a folding model with
      22 membrane spanning beta-strands and two periplasmioc domains has been
      developed.

PMID- 10943565
TI  - The role of Escherichia coli RNase E and RNase III in the processing of the
      citQRP operon mRNA from Lactococcus lactis biovar diacetylactis.
AB  - Citrate transport in Lactococcus lactis biovar diacetylactis (L. diacetylactis)
      is catalyzed by citrate permease P (CitP), which is encoded by the plasmidic citP
      gene. Two partial overlapping open reading frames citQ and citR are located
      upstream of citP. These two genes, together with citP, constitute the
      citQRPoperon. In this report it was shown that in L. diacetylactis and
      Escherichia coli, cit mRNA is subject to the same specific cleavages at a complex
      secondary structure which includes the central region of citQ and the 5'-end of
      citR. The role of ribonucleases in the fate of the cit mRNA processing was
      investigated in E. coli RNase mutant strains. The results obtained indicate that
      both endoribonucleases RNase E and RNase III are involved in the generation of
      mRNA processed species. RNase E is responsible for the major cleavages detected
      within citQ and upstream of citR, whereas RNase III cleaves citR within its
      ribosomal binding site. Preliminary results indicate the existence of a RNaselll
      like enzyme in L. diacetylactis. Based on these results, a model for the role of
      cit mRNA processing in the expression of citP is presented.

PMID- 10943564
TI  - The LysE superfamily: topology of the lysine exporter LysE of Corynebacterium
      glutamicum, a paradyme for a novel superfamily of transmembrane solute
      translocators.
AB  - In Corynebacterium glutamicum the LysE carrier protein exhibits the unique
      function of exporting L-lysine. We here analyze the membrane topology of LysE, a
      protein of 236 amino acyl residues, using PhoA- and LacZ-fusions. The amino
      terminal end of LysE is located in the cytoplasm whereas the carboxy-terminal end
      is found in the periplasm. Although 6 hydrophobic domains were identified based
      on hydropathy analyses, only five transmembrane spanning helices appear to be
      present. The additional hydrophobic segment may dip into the membrane or be
      surface localized. We show that LysE is a member of a family of proteins found,
      for example, in Escherichia coil, Bacillus subtilis, Mycobacterium tuberculosis
      and Helicobacter pylori. This family, which we have designated the LysE family,
      is distantly related to two additional protein families which we have designated
      the YahN and CadD families. These three families, the members of which exhibit
      similar sizes, hydropathy profiles, and sequence motifs comprise the LysE
      superfamily. Functionally characterized members of the LysE superfamily export L
      lysine, cadmium and possibly quarternary amines. We suggest that LysE superfamily
      members will prove to catalyze export of a variety of biologically important
      solutes.

PMID- 10943566
TI  - Construction of efficient centromeric, multicopy and expression vectors for the
      yeast Kluyveromyces marxianus using homologous elements and the promoter of a
      purine-cytosine-like permease.
AB  - Efficient centromeric and multicopy vectors have been constructed for the yeast
      Kluyveromyces marxianus using homologous ARS and centromere sequences. A
      homologous promoter of a purine-cytosine permease gene called PCPL3 has been
      cloned, using an expression system based on GUS. Its strength has been estimated
      in K. marxianus by putting the homologous beta-glucosidase gene under its
      control. This promoter is very efficient as activities higher than the ones
      obtained with the Saccharomyces cerevisiae PGK promoter were obtained. This
      promoter appears to be constitutive in various conditions tested. Its five
      transcription start sites have been mapped, and a derivative expression vector
      for K. marxianus has been constructed.

PMID- 10943567
TI  - Aptamers.

PMID- 10943568
TI  - Aptamers as therapeutic and diagnostic agents.
AB  - Aptamers are oligonucleotides derived from an in vitro evolution process called
      SELEX. Aptamers have been evolved to bind proteins which are associated with a
      number of disease states. Using this method, many powerful antagonists of such
      proteins have been found. In order for these antagonists to work in animal models
      of disease and in humans, it is necessary to modify the aptamers. First of all,
      sugar modifications of nucleoside triphosphates are necessary to render the
      resulting aptamers resistant to nucleases found in serum. Changing the 2'OH
      groups of ribose to 2'F or 2'NH2 groups yields aptamers which are long lived in
      blood. The relatively low molecular weight of aptamers (8000-12000) leads to
      rapid clearance from the blood. Aptamers can be kept in the circulation from
      hours to days by conjugating them to higher molecular weight vehicles. When
      modified, conjugated aptamers are injected into animals, they inhibit
      physiological functions known to be associated with their target proteins. A new
      approach to diagnostics is also described. Aptamer arrays on solid surfaces will
      become available rapidly because the SELEX protocol has been successfully
      automated. The use of photo-cross-linkable aptamers will allow the covalent
      attachment of aptamers to their cognate proteins, with very low backgrounds from
      other proteins in body fluids. Finally, protein staining with any reagent which
      distinguishes functional groups of amino acids from those of nucleic acids (and
      the solid support) will give a direct readout of proteins on the solid support.

PMID- 10943569
TI  - In vitro selection of nucleic acids for diagnostic applications.
AB  - In vitro selection methods have proven to be extraordinarily adept at generating
      a wide variety of nucleic acid-binding species (aptamers) and catalysts
      (ribozymes). To date, selected nucleic acids have primarily been of academic
      interest. However, just as antibodies have proven utility as 'universal
      receptors' that can be crafted against a huge variety of ligands and can be
      readily adapted to diagnostic assays, aptamers may yet find application in
      assays. A new class of research reagents, aptazymes, are not mere mimics of
      antibodies but in fact allow the direct transduction of molecular recognition to
      catalysis. Aptamers and aptazymes may prove to be uniquely useful for the
      development of chip arrays for the detection and quantitation of a wide range of
      molecules in organismal proteomes and metabolomes.

PMID- 10943570
TI  - Chemically modified nucleic acid aptamers for in vitro selections: evolving
      evolution.
AB  - Combinatorial library selections through the systematic evolution of ligands by
      exponential enrichment (SELEX) technique identify so-called nucleic acid aptamers
      that bind with high-affinity and specificity to a wide range of selected
      molecules. However, the modest chemical functionality of nucleic acids poses some
      limits on their versatility as binders and catalysts, and, furthermore, the
      sensitivity of pure RNA- and DNA-based aptamers to nucleases restricts their use
      as therapeutic and diagnostic agents. Here we review synthetic chemistries for
      modifying nucleotides that have been developed to enhance the affinity of
      aptamers for targets and to increase their stability in biological fluids.
      Implementation of in vitro selections with modified nucleotides promises to be an
      elegant technique for the creation of ligands with novel physical and chemical
      properties and is anticipated to have a significant impact on biotechnology,
      diagnostics and drug development. The current molecular designs and applications
      of modified nucleotides for in vitro selections are reviewed, along with a
      discussion of future developments expected to further the utility of this
      approach in both practical and theoretical terms.

PMID- 10943571
TI  - Structure, recognition and discrimination in RNA aptamer complexes with
      cofactors, amino acids, drugs and aminoglycoside antibiotics.
AB  - Through the use of in vitro selection techniques, a number of RNA aptamers have
      been selected for their ability to bind ligands with high affinity and
      specificity. The three-dimensional solution structures of a number of these
      complexes have been solved within the last 4 years. This review focuses on the
      structural characterization of the RNA aptamers bound to the cofactors FMN and
      AMP, the amino acids arginine and citrulline, the drug theophylline and the
      aminoglycoside antibiotic tobramycin in solution. Analysis of the structural
      features of these complexes allows the identification of molecular themes in RNA
      aptamer structure, recognition and discrimination.

PMID- 10943572
TI  - Are factor V Leiden carriers who use oral contraceptives at extreme risk for
      venous thromboembolism?
AB  - BACKGROUND: Major concern was raised by an earlier study regarding oral
      contraceptive use in women with the factor V Leiden mutation. A more than 30-fold
      increase in relative risk for venous thromboembolism was reported; for
      homozygotes, the relative risk was as much as 100-fold or more. OBJECTIVE: To
      replicate the reported risk estimates with a new population-based case-control
      study. METHODS: Eighty women with a diagnosis of venous thromboembolism were
      consecutively identified and compared with population-based controls (n = 406).
      Factor V Leiden mutation was identified by genotype analysis. The evaluation was
      performed with conditional logistic regression (matched for 5-year age group).
      RESULTS: Matched, adjusted odds ratios (OR) for idiopathic venous thromboembolism
      in women without and with the factor V Leiden mutation who used oral
      contraceptives were 4.1 (95% confidence interval (CI) 2.1-7.8) and 10.2 (95% CI
      1.2-88.4), respectively. The adjusted OR for factor V Leiden carriers was 2.0
      (95% CI 1.0-4.4). The OR for women with the factor V Leiden mutation and oral
      contraceptive use versus no factor V Leiden mutation and no oral contraceptive
      use was 10.2 (95% CI 3.8-27.6). CONCLUSION: The results confirm the increased
      relative risk of idiopathic venous thromboembolism for users of oral
      contraceptives and factor V Leiden carriers. However, we suspect that the true
      risk for women who are factor V Leiden carriers may be increased two- to four
      fold rather than seven-fold or more, and that the risk for the combination of
      factor V Leiden and oral contraceptive use may be increased in the order often-
      to 15-fold rather than over 30-fold.

PMID- 10943573
TI  - Norplant: reasons for discontinuation and side-effects.
AB  - OBJECTIVE: To study the side-effects and reasons for the discontinuation of
      Norplant. METHODS: The study was based on the analysis of the medical records of
      265 Norplant users, who obtained Norplant from two clinics of the Family Planning
      Association of Pakistan and who were followed for 5 years. RESULTS: The most
      common reason (29.4%) for the discontinuation of Norplant was menstrual
      disturbances, followed by medical problems (4.1%), desire for more children
      (3.1%) and family problems (3.1%). The major side-effects were weight gain,
      breast tenderness, headache and dizziness. Only 7.7% of users mentioned any
      change in sexual behavior and 69.6% of the complaints leading to Norplant removal
      developed within 6 months of insertion. CONCLUSION: The extent and nature of the
      side-effects experienced by Pakistani women using Norplant are similar and
      comparable to those reported from other countries.

PMID- 10943574
TI  - Acceptability of Norplant at a well-woman clinic in Turkey.
AB  - OBJECTIVE: To make an assessment of the acceptability and cost of subdermal
      implants, a new method in Turkey, in a free-choice environment. METHODS: The
      records of women attending a university well-woman clinic in Istanbul, Turkey,
      were analyzed retrospectively. Among other contraceptives registered in the
      country, the women were offered subdermal contraceptive implants (Norplant)
      during counselling sessions. The women who chose implants were invited to attend
      for follow-up three times during the first 12 months and were advised to return
      annually thereafter. An estimation of cost was performed for Norplant, using the
      government price of the implant and the wage rates of public-sector staff. An
      estimation of cost was also performed for oral contraceptives. RESULTS: Among the
      5650 women who applied to the Clinic for contraception between 1 January 1995 and
      31 December 1998, 274 women decided to use implants, giving an initial acceptance
      rate of 5.1%. Continuation rates were 91.8%, 71.6% and 42.5% at 12 months, 24
      months and 36 months, respectively. There were no pregnancies within the study
      period. The only demographic characteristic that was positively related to the
      acceptability of Norplant was younger age. The cost of contraception with
      Norplant was found to be lower than that for oral contraceptives. CONCLUSION: The
      high initial acceptance and continuation rates, combined with its high efficacy,
      make Norplant a valuable tool for Turkey's National Family Planning Program.
      Contraception with Norplant is also a cost-effective method, at least for the
      public sector.

PMID- 10943575
TI  - A comparative investigation of contraceptive reliability, cycle control and
      tolerance of two monophasic oral contraceptives containing either drospirenone or
      desogestrel.
AB  - OBJECTIVE: To assess the contraceptive reliability, cycle control and tolerance
      of a new monophasic oral contraceptive (Yasmin) containing 30 microg
      ethinylestradiol and 3 mg drospirenone and compare it with a preparation
      containing an equal dose of ethinylestradiol combined with 150 microg desogestrel
      (Marvelon). METHODS: A multicenter, open-label, randomized study was carried out
      in 26 European centers. Contraceptive efficacy, cycle control and tolerance
      (including body weight, blood pressure and heart rate) were assessed over 26
      cycles, plus a 3-month follow-up period. RESULTS: Of 900 women who were
      randomized, 887 started treatment and 627 completed the 26 cycles plus follow-up
      (310 in the ethinylestradiol/drospirenone group and 317 in the
      ethinylestradiol/desogestrel group). Both study preparations were found to be
      effective with regard to contraceptive reliability and cycle control was good.
      There were six pregnancies (three in each group), but none were considered to
      have been the result of method failures. The subjective and objective tolerances
      were good in both groups. A statistically significant difference was found in
      body weight changes between the two groups. While there was an increase in mean
      body weight in the ethinylestradiol/desogestrel group from cycle 5 onward, the
      mean body weight per cycle in the ethinylestradiol/drospirenone group was
      slightly below the baseline value throughout the study. The incidence
      ofpremenstrual symptoms was higher in the ethinylestradiol/drospirenone group
      than in the ethinylestradiol/desogestrel group during the 6 months prior to the
      study, but lower during treatment. The rates ofdysmenorrhea were identical under
      both treatments but the symptoms were more often mild and less often severe in
      the ethinylestradiol/drospirenone group. CONCLUSION: The combination of 30 microg
      ethinylestradiol combined with 3 mg drospirenone provides effective oral
      contraception and good cycle control, and is well tolerated.
      Ethinylestradiol/drospirenone had a more favorable effect on body weight than
      ethinylestradiol/desogestrel, with the mean body weight remaining lower than
      baseline for the majority of the women.

PMID- 10943576
TI  - Randomized comparative trial in parous women of the frameless GyneFix and the
      TCu380A intrauterine devices: long-term experience in a Chinese family planning
      clinic.
AB  - OBJECTIVE: To compare the clinical performance of two intrauterine devices (the
      frameless GyneFix intrauterine device (IUD) and the TCu380A IUD) during long-term
      use. STUDY DESIGN: This was a randomized comparative study. A total of 157
      insertions of the GyneFix IUD were compared with 156 insertions of the TCu380A
      IUD in the Tianjin Municipal Institute for Family Planning, China. Only parous
      women were included in the study. Insertions were conducted by the first three
      authors. The trial extended over a 9-year period, with over 10,000 woman-months
      of experience. RESULTS: The study showed that both devices are highly
      efficacious. No pregnancies occurred with the GyneFix IUD (cumulative pregnancy
      rate 0.0), compared to one pregnancy with the TCu380A IUD (cumulative pregnancy
      rate 0.64). The cumulative expulsion rate with the GyneFix IUD was 1.91 (three
      expulsions occurred, two of which were during the first 6 months), compared to a
      cumulative expulsion rate of 5.13 (eight expulsions) with the TCu380A (p =
      0.1112). The total use-related discontinuation rate (terminations were mainly due
      to bleeding disturbances) was significantly lower (p = 0.0051) with the GyneFix
      IUD (4.46) than with the TCu380A IUD (14.10) and resulted in a higher rate of
      continuation with the GyneFix IUD compared to the TCu380A IUD (92.36 versus
      83.97). Neither perforations nor cases of pelvic inflammatory disease were
      encountered with either device in this study, demonstrating the safety of the
      anchoring system. CONCLUSION: The results of the present clinical trial are in
      agreement with the findings of other multicenter, randomized, comparative,
      clinical trials that have investigated these two IUDs in China, as well as with
      the findings of other large-scale international studies conducted with the
      frameless IUD.

PMID- 10943577
TI  - Profile and opinions of the female Persona user in The Netherlands.
AB  - OBJECTIVES: The primary objective of this study was to investigate the profile of
      the Dutch Persona user and her opinion about this relatively new way of natural
      birth control. The results of the study were used to draw conclusions for the
      suitability for Persona as a contraceptive method. METHOD: Data from 137 users of
      the device were obtained from structured questionnaires. RESULTS: The 'Persona
      woman' is typically in a steady relationship, highly educated and has an above
      average income. She wants to have a contraceptive method with no side-effects and
      desires children in the future. She is therefore looking for information about
      her own cycle. It is remarkable that one in four women uses the system to help in
      planning a pregnancy instead of avoiding one. CONCLUSIONS: Persona seems to be a
      welcome alternative for natural family planning and for couples who have no
      absolute negative attitude towards a(nother) child, but want to postpone their
      first pregnancy or to space pregnancies. The method is not reliable enough to be
      used as the only contraceptive method when a couple absolutely wants to prevent a
      pregnancy. Another conclusion that can be drawn is that the method improves
      fertility awareness.

PMID- 10943578
TI  - Factors affecting the selection of a reversible or an irreversible contraceptive
      method in a developing country.
AB  - OBJECTIVES: To evaluate the factors that may affect the selection of a reversible
      or an irreversible contraceptive method. METHODS: In an urban area of a
      developing country, demographic characteristics, educational and income levels,
      and previously used contraceptive methods were retrospectively reviewed for 3
      years from the files of women who had chosen reversible or irreversible
      contraceptive methods. Student's t test and the chi2 test were used to analyze
      the data obtained from the two groups of women. RESULTS: Out of a total of 8078
      women, 595 (7.4%) selected surgical sterilization, while 7483 (92.6%) preferred
      reversible methods such as intrauterine devices (38.1%), combined oral
      contraceptives (13.9%), condoms (40%) and Norplant (0.6%). Compared to those who
      preferred reversible methods, the women with surgical sterilization had a higher
      mean age (33.9 +/- 4.2 years versus 29.6 +/- 3.9 years), mean gravidity (3.8 +/-
      0.9 versus 2.3 +/- 1.2) and mean number of living children (2.6 +/- 0.8 versus
      2.1 +/- 1.1) (p < 0.01). These women had also higher rates of high-school
      education (37.3% versus 30.1%) and previous modern contraceptive use (78.1%
      versus 71.2%) (p < 0.01). None of the women with surgical sterilization, but 1770
      (33.0%) of those who chose reversible methods, had fewer than two living
      children. CONCLUSIONS: These data suggest that irreversible contraceptive methods
      tend to be chosen by older women with higher educational levels, who have decided
      that their family is complete and who have at least two children.

PMID- 10943579
TI  - The cost of the menstrual cycle in young Swedish women.
AB  - The purpose of this study was to evaluate the cost of the menstrual cycle for
      young Swedish women aged 14-20 years. The young women were randomly selected and
      interviewed by a trained female psychologist; a total of 68 young women completed
      the interviews. Twenty of the girls used oral contraceptives, while 48 had
      natural periods. The oral contraceptive users had a lighter menstrual flow and
      shorter periods (1 day less) than the girls with natural menstruation. The oral
      contraceptive users experienced less menstrual pain, used fewer painkillers and
      did not stay at home during their periods as often as the girls with natural
      periods. The cost of sanitary protection products was about US$1 per month less
      for the oral contraceptive users. Girls taking oral contraceptives also avoided
      stained underwear and soiled bedlinen significantly more often than the non-oral
      contraceptive users. The study design did not allow for cost estimates on soiled
      underwear, bedlinen or lost work- or schooldays. The results of the study
      indicate that expenditures related to the menstrual cycle are considerable for
      young Swedish women.

PMID- 10943580
TI  - The role of gonadotropins in follicular development and their use in ovulation
      induction protocols for assisted reproduction.
AB  - During the 1960s, hypogonadotropic patients with polycystic ovary syndrome and
      those with clomiphene citrate resistance were the first to achieve pregnancy
      after urinary human menopausal gonadotropin (hMG) administration plus
      preovulatory human chorionic gonadotropin injection, with cumulative pregnancy
      rates ranging from 40% to 80% after six to 12 treatment cycles. Ever since,
      dramatically more progress has been achieved regarding methods and medication in
      assisted conception techniques, involving both a rapidly increased number of
      subfertile couples, as well as many practitioners in obstetrics and gynecology.
      The purpose of this review was to highlight the most crucial historical steps of
      this remarkable process, by emphasizing the role of gonadotropins in ovulation
      induction protocols according to the various clinical categories of subfertile
      patients. In the late 1970s, urinary hMG was the most widely used gonadotropin
      for ovarian stimulation during in vitro fertilization-embryo transfer for
      assisted reproduction. The often concurrent problems of premature luteinizing
      hormone (LH) surges and premature luteinizations, and thus cancellations of the
      cycles, were efficiently overcome by 'reversible medical hypophysectomy',
      performed by gonadotropin releasing hormone (GnRH) analogs, introduced in 1982.
      According to its initiation and duration, GnRH analog use was divided into three
      protocols: the long, most widely used, protocol, which was the best for
      suppression of endogenous, high tonic LH levels, especially in polycystic ovary
      syndrome and normogonadotropic patients; and the short and ultra-short protocols,
      which were mainly used in poor responders to ovarian stimulation treatment, older
      or hypergonadotropic patients with ovarian failure, because of the well-known
      'flare-up phenomenon'. Recently, GnRH antagonists, which directly do not permit
      GnRH action by binding to the GnRH gonadotropic cell receptors, have been used,
      but no final results from large, multicenter clinical trials that are still being
      undertaken have yet been achieved. Various sub-products of urinary hMG have been
      produced since the 1980s, with the intention of eliminating most or all of the
      LH, such as a form with a 3:1 proportion ratio between follicle stimulating
      hormone (FSH) and LH, as well as a form resulting in the removal of almost all of
      the LH, the 'pure' urinary FSH. Finally, in the mid-1990s, recombinant pure FSH
      was produced in vitro from hamster ovarian cell cultures. The theoretical basis
      for the broad use of pure urinary FSH and recombinant FSH is that the very low
      endogenous LH levels after pituitary desensitization are sufficient for proper
      theca steroidogenesis; still, data in the literature and clinical experience may
      be controversial upon that issue. From the clinical point of view, clinicians
      nowadays tend to stimulate polycystic ovary syndrome patients with recombinant
      FSH plus the application of GnRH analogs in a long protocol. However, in poor
      responders, patients in whom ovulation is resistant to clomiphene citrate, those
      older than 40 years or hypergonadotropic patients with ovarian failure, urinary
      hMG, because endogenous LH levels are obviously not sufficient for proper
      steroidogenesis in the theca cells of the follicles of these patients, is
      necessary in add to the administration of GnRH analogs in a short or ultra-short
      protocol. Regarding normogonadotropic women (the majority of patients), most
      authors agree with the long-protocol application of GnRH analogs. In these
      patients, it is not certain whether recombinant FSH alone is sufficient for the
      best possible induction or whether exogenous LH administration in the form of
      urinary hMG still remains necessary.

PMID- 10943581
TI  - Carotid artery disease: is the debate over?

PMID- 10943582
TI  - The reliability of leg circumference assessment: a comparison of spring tape
      measurements and optoelectronic volumetry.
AB  - The purpose of this study was to compare the reliability of repeated spring tape
      measurements with optoelectronic volumeter measurements for the assessment of
      lower leg circumferences. The limb circumferences at mid-calf and ankle level of
      both legs were measured three times using a spring tape measure as well as an
      optoelectronic volumeter. In all, 30 healthy volunteers participated in the
      study. Test reliability and repeatability were described through the process
      related and between-subject variances and variance-derived parameters such as the
      reliability coefficient (intraclass correlation coefficient, RC), the relative
      precision (RP), and the coefficient of repeatability (CR). A higher value for the
      RC and a lower value for the RP indicate that the test variability is
      predominantly due to between-subject variance and not to test process-related
      variance. RCs for both methods, independent of whether measurements were taken at
      calf or at ankle level, always exceeded 0.95. RPs were in the same order of
      magnitude for both methods but lower for measurements at calf than at ankle level
      (range: RPcalf 6.36-8.74%; range: RPankle 12.49-18.56%). CRs for both methods
      were low and of comparable magnitude (CR range: 4.8-7.7), although slightly
      smaller for the spring tape. When measurement results from the spring tape and
      the volumeter were compared, results achieved with the volumeter were
      significantly longer than those from the spring tape (p<0.05). Results from both
      methods were linearly in good agreement and there was no proportional bias;
      differences shown were due to a significant constant bias regarding the
      volumeter. Circumference measurements taken by spring tape and by optoelectronic
      volumetry are both characterized by a comparably high reliability. However, these
      methods cannot be used in an interchangeable way because a constant bias exists
      for volumetry, resulting in significantly larger circumferences compared with
      those measured using the spring tape.

PMID- 10943583
TI  - Short-term treatment with transdermal nicotine affects the function of canine
      saphenous veins.
AB  - Experiments were designed to determine the effects of nicotine treatment on the
      functions of saphenous veins used for coronary artery bypass grafts in dogs. Dogs
      received either no treatment or transdermal nicotine for 5 weeks at doses of 11
      mg, 22 mg or 44 mg/day. Saphenous veins were removed and suspended for the
      measurement of isometric force in organ chambers. Endothelium was removed
      mechanically from some rings. N(G)-mono-methyl-L-arginine (L-NMMA; 10(-4) M) was
      used to inhibit the production of nitric oxide. Contractions to alpha2-adrenergic
      stimulation were decreased in veins from dogs treated with a 22-mg/day dose of
      transdermal nicotine. In addition, endothelium-dependent relaxations to adenosine
      diphosphate (10(-8)-10(-4) M) and the calcium ionophore A23,187 (10(-8)-10(-6) M)
      were decreased in veins from dogs with a 22-mg/day dose and increased in veins
      from dogs treated with a 44-mg/day dose. These relaxations were inhibited by L
      NMMA. Plasma concentrations of oxidized products of nitric oxide were decreased
      only in dogs treated with 22 mg/day of nicotine. The relaxation of rings without
      endothelium (direct response on the smooth muscle) to nitric oxide were not
      altered by nicotine treatment. These results suggest that the short-term
      treatment of dogs with intermediate (22 mg/day) but not low (11 mg/day) or high
      (44 mg/day) doses of transdermal nicotine decreases the endothelial function of
      veins used for coronary artery bypass grafts. Therefore, changes in plasma
      products of nitric oxide and endothelium-dependent relaxations mediated by nitric
      oxide are related to the dose of nicotine treatment.

PMID- 10943584
TI  - Effect of cloricromene on intermittent claudication. A randomized, double-blind,
      placebo-controlled trial in patients treated with aspirin: effect on claudication
      distance and quality of life. CRAMPS Investigator Group. Cloricromene Randomized
      Arteriopathy Multicenter Prospective Study.
AB  - The main aim of medical treatment for intermittent claudication (IC) is the
      reduction of mortality and morbidity from ischemic cardiovascular disease.
      However, symptomatic treatment with the aim of improving exercise performance and
      the overall quality of life may also be an important target of the clinical
      management of patients with intermittent claudication. Cloricromene, a drug with
      antithrombotic and anti-ischemic activities, has previously shown some promising
      results in patients with claudication. We have carried out a clinical trial to
      assess the effect of cloricromene on the claudication distance and on the quality
      of life of patients with IC chronically treated with aspirin. A total of 159
      patients with IC, Stage II (Fontaine), were enrolled in a double-blind,
      randomized, prospective, multicenter study comparing cloricromene (100 mg orally
      b.i.d.) or an identical placebo for 6 months. All patients received 160 mg/day
      aspirin. The primary end-point was the improvement of initial claudication
      distance (ICD) at 6 months as measured by a standardized treadmill test. The
      secondary end-points were the absolute claudication distance (ACD) at 6 months,
      the percentage of patients defined as responders to treatment (improvement of ICD
      of at least 40%), changes in the ischemic window (IW), quality of life as
      assessed by the SF-36 questionnaire, and the occurrence of major cardiovascular
      events. The ICD increased in both treatment groups, with a non-significant
      difference at 6 months in favor of cloricromene of +12.3 m. The ACD, percentage
      of responders to treatment and ischemic window also improved in both groups with
      a slight, non-significant trend in favor of cloricromene. Pretreatment quality of
      life scores showed only a slight worsening compared with an age-matched, healthy
      population and did not change upon treatment. A post hoc subgroup analysis showed
      a significant benefit from cloricromene in patients with an ICD at enrollment
      higher than the median of the patient population. In conclusion, treatment with
      cloricromene for 6 months does not significantly improve claudication in patients
      with Stage II Fontaine peripheral arteriopathy chronically treated with aspirin.
      An improvement of 40-60 m in the ICD on a standardized treadmill test does not
      translate into a self-perceived improvement in the quality of life as assessed by
      the SF-36 questionnaire.

PMID- 10943585
TI  - Long-term benefit of thrombolytic therapy in patients with pulmonary embolism.
AB  - A total of 23 of the 40 patients who had angiographically proven pulmonary
      embolism and who had initially been randomized to an IV infusion of heparin (n =
      11) or a thrombolytic agent (urokinase or streptokinase, n = 12) were restudied
      after a mean follow-up of 7.4 years to measure the right-sided pressures and to
      evaluate their response to exercise during supine bicycle ergometry. Results
      showed that, at rest, the pulmonary artery (PA) mean pressure and the pulmonary
      vascular resistance (PVR) were significantly higher in the heparin group compared
      with the thrombolytic group (22 vs. 17 mmHg, p<0.05, and 351 vs. 171 dynes s(-1)
      cm(-5), p<0.02, respectively). During exercise both parameters rose to a
      significantly higher level in the heparin group (from rest to exercise, PA: 22-32
      mmHg, p<0.01; PVR: 351-437 dynes s(-1) cm 5, p<0.01, respectively), but not in
      the thrombolytic group (rest to exercise, PA: 17-19 mm Hg, p = NS; PVR: 171-179
      dynes s(-1) cm(-5), p = NS). It is concluded that thrombolytic therapy preserves
      the normal hemodynamic response to exercise in the long term and may prevent
      recurrences of venous thromboembolism and the development of pulmonary
      hypertension.

PMID- 10943586
TI  - Local drug delivery: an emerging approach in the treatment of restenosis.
AB  - Very limited success has been demonstrated with systemic pharmacological
      treatment to reduce the incidence of restenosis following angioplasty in
      patients. The lack of success of many of the pharmacotherapeutic agents in
      reducing the restenosis rates post-angioplasty and following stent implementation
      is believed to arise from inadequate concentrations of the agents at the lesion
      site. This has led to the development of various local delivery devices that
      would ideally deliver and retain adequate amounts of drug to the vessel wall for
      sufficient periods of time to ensure a therapeutic effect without inducing
      further injury or compromising blood flow. Local dosing would avoid systemic
      toxicity, and the use of modified balloon catheters or coated stents might enable
      percutaneous approaches.

PMID- 10943587
TI  - Antisense and gene therapy to prevent restenosis.
AB  - A primary pathologic response to vascular injury is the proliferation and
      migration of vascular smooth muscle cells and the development of neointimal
      lesions. An increasing body of knowledge regarding the molecular and genetic
      basis of neointimal disease has created a unique opportunity for the treatment of
      this complex disorder. Gene therapy attempts to correct pathobiological processes
      by either inhibiting or correcting cellular functions at the level of gene
      expression. These endpoints are achieved by the delivery of either functional
      genes or oligonucleotides, capable of interfering with a cell's programmed
      machinery. Since the early 1990s, the evolution of this technology, along with an
      ever-expanding source of pathobiological information, has led to many novel
      approaches for the treatment of restenosis in arterial balloon injury as well as
      vein graft bypass failure. Using a variety of targets, inhibition of
      proliferation has predominantly been achieved through direct disruption of the
      cell cycle machinery. In addition, others have demonstrated successful inhibition
      by interfering with the signals for cellular proliferation or the enhancement of
      anti-proliferative stimuli. As this exciting therapeutic alternative evolves,
      improvements in safety, specificity and efficiency will enhance the likelihood of
      widespread clinical application.

PMID- 10943588
TI  - A contemporary approach to thrombolytic therapy for pulmonary embolism.
AB  - Successfully utilized contemporary pulmonary embolism thrombolysis reverses right
      heart failure rapidly and safely. This therapeutic approach may lower mortality
      from pulmonary embolism and reduce morbidity from chronic pulmonary hypertension.
      Unlike myocardial infarction thrombolysis, a 2-week 'time window' is available,
      during which treatment can be initiated. A high concentration of the thrombolytic
      agent is administered in a brief infusion lasting several hours. No special
      laboratory testing is needed. Currently, the only contemporary thrombolytic
      regimen for pulmonary embolism that is approved by the Food and Drug
      Administration is tissue plasminogen activator, in a dose of 100 mg/2 h. New
      thrombolytic agents under development for pulmonary embolism include reteplase,
      saruplase, and recombinant staphylokinase. Future clinical trials will require
      multicenter collaboration and will focus on relevant endpoints such as the
      reduction of mortality and recurrent venous thromboembolism.

PMID- 10943589
TI  - Arteritis of the temporal and subclavian artery.

PMID- 10943590
TI  - The iron hypothesis: claim vs. hypothesis.

PMID- 10943591
TI  - Chromium, exercise, and body composition.
AB  - Chromium is an essential trace element involved in the metabolism of
      carbohydrates, lipids, and proteins mainly by increasing the efficiency of
      insulin. Chromium deficiency affects the maintenance of normal glucose tolerance
      and healthy lipid profiles. The Estimated Safe and Adequate Daily Dietary Intake
      for chromium is 50 to 200 microg/d for adults. However, the dietary intake of
      chromium in humans is often suboptimal. Chromium assessment has proven to be a
      challenge due to the low amounts of chromium present in biological materials and
      the absence of a reliable indicator of chromium status. Recently, chromium has
      been touted as an agent for increasing lean body mass and decreasing percent body
      fat. This article reviews the various studies that have been conducted to
      investigate the relationship of chromium with exercise and body composition.

PMID- 10943592
TI  - Grain processing and nutrition.
AB  - Whole grains provide a wide range of nutrients and phytochemicals that optimize
      health. Epidemiologic studies support the protectiveness of whole grain
      consumption for cardiovascular disease and cancer. Dietary guidance endorses
      increased whole grains in our diet. A crucial question remaining is the effect of
      processing of whole grains on their content of nutrients and phytochemicals.
      Although processing is often considered to be a negative attribute in nutrition,
      and some forms of processing reduce nutritional value, many factors support the
      importance of processing of grains to enhance grain consumption. First, whole
      grains as harvested are generally not consumed directly by humans but require
      some processing prior to consumption. While refining, that is, removal of the
      bran and the germ, reduces the nutrient content of grain, milling of grains
      otherwise concentrates desirable grain components and removes poorly digested
      compounds and contaminants. Cooking of grains generally increases digestibility
      of nutrients and phytochemicals. Studies in both animal models and humans support
      the notion that processed grains are often nutritionally superior to unprocessed
      grains, probably because of enhanced nutrient bioavailability in processed
      grains. Processing of grains also provides shelf-stable products that are
      convenient and good tasting for consumers.

PMID- 10943593
TI  - Hydration number and water activity models for the sucrose-water system: a
      critical review.
AB  - The nature of various molecular interactions occurring in the sucrose-water
      system and the structure of the aqueous solution are outlined briefly. The
      thermodynamic implications of these interactions are discussed, with special
      emphasis placed on the sucrose hydration number and the water activity
      coefficient. The existing "chemical" models of water activity, due to Scatchard
      (1921), Stokes and Robinson (1966), Schonert (1986), and Van Hook (1987), are
      evaluated in detail, including their predictive ability for dilute solutions and
      their limiting behavior in the region of high sucrose content. Some suggestions,
      based on the sucrose association mechanism, are made with regard to possible
      reformulations of the existing activity models that could result in a powerful
      thermodynamic model of the system.

PMID- 10943594
TI  - Stability of YKL-40 concentration in blood samples.
AB  - The stability of YKL-40, a mammalian member of the family of 18
      glycosylhydrolases, in blood samples handled under different temperatures and
      different time intervals before centrifugation was studied in paired serum and
      plasma samples from 25 healthy premenopausal Danish women. Significant elevations
      of YKL-40 were found in 8 paired serum samples left on the clot for more than 3 h
      at room temperature compared to paired serum samples left on the clot for 3 h or
      less. Significant elevations of YKL-40 were found in 8 paired plasma (EDTA)
      samples left on the blood cells for more than 8 h at room temperature compared to
      paired plasma (EDTA) samples left on the blood cells for 8 h or less. No
      elevations were found in YKL-40 levels in serum samples left on the clot at 4
      degrees C for 24 h or in plasma (EDTA) samples left on the blood cells for 72 h
      before centrifugation. Significantly lower concentrations of YKL-40 were measured
      in plasma (EDTA) compared with paired serum samples with a serum/plasma ratio of
      1.4 in samples left on the clot or on blood cells at 4 degrees C for up to 24 h.
      Repetitive freezing and thawing had no significant effect on the measured YKL-40
      concentrations. In conclusion, we have shown that YKL-40 is very dependent on the
      handling procedures. All the blood samples must be processed into plasma (EDTA)
      within 8 h at room temperature or into serum in less than 3 h at room
      temperature. If this is not possible, the blood samples must be stored at 4
      degrees C until processed.

PMID- 10943595
TI  - Inactivation of antioxidant enzymes by peroxynitrite.
AB  - Exposure of hemolysates and whole erythrocytes to peroxynitrite (bolus of 50
      micromol dm(-3)-2 mmol dm(-3)) was found to inactivate erythrocyte antioxidant
      enzymes: glutathione peroxidase > superoxide dismutase > catalase. Inactivation
      of antioxidant enzymes by peroxynitrite may be one reason for the secondary
      oxidative stress in peroxynitrite-treated cells. When hemoglobin was not
      converted into the cyanmet form, an apparent activation of glutathione peroxidase
      activity by peroxynitrite was observed in hemolysates; this effect was
      artifactual and due to the pseudoenzymatic glutathione peroxidase activity of
      hemoglobin.

PMID- 10943596
TI  - Prognostic evaluation of primary non-small cell lung carcinoma patients using
      biological fluid variables. A systematic review.
AB  - We have systematically reviewed the biomedical literature to try to establish
      whether laboratory variables might give any additional prognostic information in
      non-small-cell lung cancer (NSCLC) patients independently of the usual
      radioclinical parameters. In each study, we acknowledged the independent
      prognostic value of a biological fluid variable if it had been demonstrated
      through a multivariate statistical analysis in which at least the following had
      been included: patient's weight loss, age, gender, performance status, histology,
      stage and extent of the disease. The clearest conclusion that can be derived from
      the 42 studies we reviewed is that it remains to be clearly demonstrated whether
      or not the "new" tests (tumour markers, p53 antibodies, etc.) are superior to the
      "old" tests (serum LDH, calcium, albumin or other proteins, blood cell counts,
      etc.), even though a number of studies did suggest that serum cyfra 21-1 has a
      pre-therapeutic prognostic significance in NSCLC. From the four studies in which
      the same powerful statistical methodologies were used (i.e. Cox models in
      association with RECPAM analysis), it could be derived that serum calcium and
      perhaps the blood neutrophil and lymphocyte counts might have independent pre
      therapeutic prognostic significance in advanced NSCLC. Further studies are needed
      to demonstrate whether repeated measurements during therapeutic follow-up can
      bring any independent prognostic information. Provided that both laboratory and
      statistical expertise is clearly guaranteed in future primary studies published
      in this particular biomedical field, it might perhaps become possible to propose
      laboratory variables as additional prognostic parameters in NSCLC.

PMID- 10943598
TI  - Activation of coagulation during treatment with haemodialysis.
AB  - Generation of factor XII, thrombin antithrombin complexes, prothrombin fragment
      1+2 and thrombus precursor protein has been monitored in 16 subjects during
      haemodialysis. Immediately after starting treatment, contact of blood with the
      negatively charged surfaces of the polyacrylnitril membrane AN-69 resulted in a 9
      45% decrease in factor XII activity. Peak concentrations for thrombin
      antithrombin complexes (50 to 120 microg/L) were observed 30 min after the start
      of haemodialysis. Establishment of thrombus precursor protein concentrations
      yielded steadily increasing results without any tendency to decrease during
      treatment. Determination of thrombin antithrombin complexes is considered to
      establish the most sensitive short-term reacting parameter indicating activation
      of coagulation. A steady generation of fibrin and fibrinogen-fibrin complexes
      during treatment with haemodialysis is indicated by increasing results for
      thrombus precursor protein. In order to prevent clotting during haemodialysis, an
      additional supplementation of anticoagulant is needed.

PMID- 10943597
TI  - Evaluation of urinary bladder cancer antigen as a marker for diagnosis of
      transitional cell carcinoma of the urinary bladder.
AB  - The purpose of the present study was to assess a new quantitative urinary tumor
      marker for transitional cell carcinoma of the urinary bladder (TCC), measuring
      fragments of cytokeratin 8 and 18 in the urine (UBC). Urine samples of 355
      individuals (77 healthy volunteers, 111 patients with benign urologic disorders,
      167 patients with histologically proven bladder cancer) were examined for the
      presence of UBC antigen. Samples of all patients were obtained prior to therapy.
      Compared to healthy volunteers or patients with benign urologic disease, patients
      with TCC had significantly higher median urinary levels of UBC antigen (0 vs.
      4.18 vs. 7.46 microg/g creatinine; p<0.001, and p<0.01, respectively). UBC
      antigen levels were positively correlated with tumor grade and stage. Patients
      with invasive TCC had significantly higher levels of UBC antigen than patients
      with superficial TCC (p<0.001). Elevated levels of UBC antigen were also found in
      patients with benign urologic disorders (median: 4.18 microg/g creatinine vs.
      7.46 microg/g creatinine in cancer patients). Using a cutoff of 14.06 microg/g
      creatinine (corresponding to 95% specificity in the group of healthy
      individuals), sensitivity of UBC antigen ranged between 21.6% (pTa) and 75%
      (pT4). Overall specificity was 76.6%. Based on our data we conclude that the UBC
      antigen test in its current format is not clinically useful for detection of
      bladder cancer.

PMID- 10943599
TI  - Wide variations in the testing of lactose tolerance: results of a questionnaire
      study in Finnish health care centres.
AB  - About 70% of the world's adult population is unable to digest lactose, the sugar
      found naturally only in milk. This disability leads to gastrointestinal symptoms
      called lactose intolerance. In Finland, many patients visit health care centres
      because they are suffering from gastrointestinal symptoms. A few of them are
      diagnosed as being lactose intolerant. However, a far larger number diagnose
      themselves as suffering from lactose intolerance. Therefore the diagnostic tests
      used should be carefully validated and standardized in clinical laboratories
      throughout the country. The aim of this questionnaire study was to clarify the
      situation centres with adult patients in Finnish health care and to try to
      standardize procedures for administering lactose tolerance tests.

PMID- 10943600
TI  - Contrasting cardiac regional responses of A-type and B-type natriuretic peptide
      to experimental chronic heart failure.
AB  - OBJECTIVE: The aim of this study was to examine the regional myocardial variation
      in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) synthesis
      during development of congestive heart failure (CHF). METHODS: Heart failure was
      induced by left atrial rapid pacing for 3 weeks in pigs. The gene expression of
      ANP and BNP was measured by northern blot analysis and the peptide concentration
      in myocardial tissue and plasma by radioimmunoassay (RIA). RESULTS: At the end of
      the pacing period pulmonary capillary wedge pressure (PCWP) and right atrial
      pressure (RAP) increased, and cardiac output (CO) decreased compared to sham
      operated controls (PCWP: 17.6 +/- 1.9 vs. 3.1 +/- 0.9 mmHg) (RAP: 10.4 +/- 1.7
      vs. 2.2 +/- 0.6 mmHg) (CO: 3.5 +/- 0.4 vs. 5.3 +/- 0.3 l/min), indicating a state
      of moderate to severe CHF. The gene expression and tissue concentration of BNP
      was low in sham pigs, but was strongly increased in all cardiac regions, and
      especially in the left ventricle, during CHF. In contrast, ANP was mainly
      produced in the atria both in normal and heart failure conditions. The relative
      increases in mRNA levels, tissue concentrations and circulating peptide
      concentrations were more profound for BNP than for ANP. CONCLUSIONS: In response
      to CHF induction, ANP and BNP respond differently across the cardiac regions.
      Strong expression of the BNP gene was only found in the heart failure state,
      while ANP was clearly expressed also in the normal state. These findings support
      the concept of BNP being superior to ANP as a biochemical marker of CHF.

PMID- 10943601
TI  - Peptidoglycan and lipoteichoic acid, components of the streptococcal cell wall,
      have marked and differential effects on adhesion molecule expression and the
      production of reactive oxygen species in human whole blood leukocytes.
AB  - To elucidate the pathophysiology of infections with Streptococcus pyogenes we
      applied flow cytometric techniques to study dose-response and time-related
      effects of the streptococcal cell-wall-derived components lipoteichoic acid (LTA
      0.005 to 50 microg/ml) and peptidoglycan (10 and 100 microg/ml) on the expression
      of leukocyte adhesion molecules, the CD14 receptor, and the production of
      leukocyte reactive oxygen species (ROS). LTA (50 microg/ml, 1-2 h) markedly
      increased the expression of CD11b (approximately 5-fold), CD11c (approximately 2
      fold) and CD11a. Concomitantly, CD62L was downregulated (60%). Peptidoglycan
      alone or in combination with LTA had little effect on adhesion molecules, except
      for an amplification of the downregulation of CD62L to 90%. Monocyte CD14
      expression was doubled by LTA. Leukocyte ROS production was 10-fold and 5-fold
      increased by peptidoglycan in granulocytes and monocytes, respectively. LTA alone
      had no effect, while the combination of peptidoglycan with LTA doubled the
      increase in ROS caused by peptidoglycan. CONCLUSION: LTA and peptidoglycan had
      marked and differential effects: LTA caused mainly adhesion molecule modulation,
      whereas peptidoglycan mainly increased ROS production. These changes are
      important in inflammatory cell activation and recruitment, intracellular
      microbial killing and adverse tissue injury.

PMID- 10943603
TI  - LH release in mink (Mustela vison). Pattern of the LH surge and effect of
      metabolic status.
AB  - The mink is a seasonal breeder with induced ovulation and delayed implantation.
      Reproductive processes are strongly influenced by energy supply and body
      condition. Items for which there is paucity or complete lack of data were the
      main objectives of this study: the temporal relationship between copulation and
      the pre-ovulatory LH surge and the influence of energy supply on LH release. A
      total of 30 yearling female mink with a well defined metabolic status was used.
      Twelve females kept in the laboratory were measured in six consecutive one-week
      balance periods each including the measurement of heat production by means of
      indirect calorimetry, and 18 females were kept under conventional farm
      conditions. The animals were fed so as to maintain energy balance (CON), flush
      fed by 2 weeks food restriction followed by 2 weeks refeeding (FLUSH), or kept in
      a negative energy balance (NEG). Plasma concentrations of the thyroid hormones,
      IGF-1 and insulin were determined weekly (n = 12), or 1 week after change in
      energy supply to the FLUSH group (n = 18). On the day of mating, blood samples
      for LH and oestradiol-17beta (E2) were taken before and immediately after mating
      and then 4, 8, 12, 24, 30 and 48 h thereafter. Frequent blood samplings, each
      lasting 60 min, were taken during the LH surge from two other females surgically
      fitted with venous access ports. Peak concentrations of LH were recorded on the
      first sampling, an average 16 min after mating. The concentrations remained
      elevated for 12 h, but almost decreased to basal values 24 h after mating. Plasma
      E2 was high before mating and peak values were attained 4 h after mating after
      which it decreased. Energy supply had no significant influence on LH and E2, but
      there was a tendency for a more sluggish LH release in NEG animals. The lack of
      response in FLUSH animals was explained by these animals having a lower intake of
      metabolisable energy than CON animals, the total intake not being significantly
      different from the NEG group. Plasma concentrations of thyroid hormones, IGF-1
      and insulin were not significantly affected by the treatment, but in FLUSH
      animals the values mirrored energy supply, and in the NEG group, the values
      tended to decrease during the course of the experiment. It was concluded that the
      pre-ovulatory LH surge is an immediate response to mating, and that reproductive
      activity in the mink is maintained over a wide range of energy supply and body
      condition.

PMID- 10943602
TI  - QTc interval length and QT dispersion as predictors of mortality in patients with
      non-insulin-dependent diabetes.
AB  - Patients with non-insulin-dependent diabetes (NIDDM) are at independent risk of
      cardiovascular death. The reason is only partially understood. The aim of our
      study was therefore to evaluate the impact of corrected QT interval length (QTc)
      and QT dispersion (QT-disp) on mortality in a cohort of 324 Caucasian NIDDM
      patients. A resting 12-lead ECG was recorded at baseline. Maximum (QT-max) and
      minimum QT (QT-min) intervals were measured, and QT-max was corrected for heart
      rate (QTc-max). QT-disp was defined as the difference between QT-max and QT-min.
      QTc-max was 454 (376-671) ms(1/2) (median (range)) and QT-disp 61 (0-240) ms.
      Prolonged QTc interval (PQTc), defined as QTc-max > 440 ms(1/2), was present in
      67% of the patients and prolonged QT-disp (PQT-disp), defined as QT-disp > 50 ms,
      was present in 51%. During the 9-year follow-up period, 100 patients died (52
      from cardiovascular diseases). Thirty-seven percent of the patients with PQTc
      died compared with 17% with normal QTc interval (p<0.001). The Cox proportional
      hazard model, including putative risk factors at baseline, revealed the following
      independent predictors of all cause mortality; QTc-max (p<0.05), age (p<0.0001),
      albuminuria (p<0.01), retinopathy (p<0.01), HbA1c (p<0.05), insulin treatment
      (p<0.01), total cholesterol (p<0.01), serum creatinine (p<0.05) and presence of
      cardiac heart disease based on Minnesota coded ECG (p<0.001). Whereas QT-disp was
      not a predictor, QTc-max interval was an independent predictor of cardiovascular
      mortality. Our study showed a high prevalence of QTc and QT-disp abnormalities
      and indicated that QTc-max but not QT-disp is an independent predictor of all
      cause and cardiovascular mortality in NIDDM patients.

PMID- 10943604
TI  - Age-related changes in apparent digestibility in growing kittens.
AB  - The ability of the growing kitten to digest protein, fat, carbohydrate, dry
      matter and energy were assessed. Kittens were divided into two groups; one group
      was fed a wet diet, the other a dry diet. Both groups were allowed ad libitum
      access to food. Apparent digestibility of the two diets, and kitten bodyweights
      were measured over a 24-week period. There were no significant differences in
      mean bodyweight between the two groups. Digestible energy intake of the kittens
      decreased with increased age; regression analysis of the data generated two
      fitted models which appeared to accurately predict the digestible energy intake
      between 39 and 41 weeks of age. There was a significant (P < 0.05) effect of diet
      on the apparent digestibility of protein, organic-matter and dry-matter. Age had
      a significant (P < 0.05) effect on the apparent digestibility of all the
      parameters measured. Newman-Keuls multiple range tests showed that apparent
      digestibility of carbohydrate, organic-matter and total energy significantly (P <
      0.05) increased in kittens older than 19 weeks. This suggests that the digestive
      capacity of the younger cat may be affected by the physiological development of
      the gut, and dietary induced enzyme modulation.

PMID- 10943605
TI  - Use of a variable electrical pulsing sequence in rabbit oocyte activation.
AB  - Variability in oocyte activation sensitivity to electrical stimuli was shown in
      two types of oocytes (i.e., oocytes with a whole first polar body: w-PB 1 and
      those with a fragmented PB 1: f-PB 1), of a similar post-ovulatory age. In order
      to initiate the normal activation display (i.e., extrusion of the second polar
      body), the w-PB 1 oocytes required, on average, 3.6 +/- 0.2 pulses and the f-PB 1
      oocytes 2.9 +/- 0.1 pulses (p = 0.18). From both experimental series carried out
      in this work, the average haploid activation rates were 68% and 70% for w-PB1 and
      f-PB1 oocytes, respectively. Oocyte type did not affect the haploid embryo
      developmental ability observed at 24 h of culture (8-cell stage: 33-35% in Series
      1 and 23-26% in Series 2), nor at 32 h of culture (16-cell stage: 77-93% and
      morula stage: 34-41%; Series 2). Therefore, in further experiments, the f-PB 1
      oocytes may also be used as potential forerunners of haploid embryos, almost up
      to the morula stage.

PMID- 10943606
TI  - The effect of a mixed-management system on the release of oxytocin, prolactin,
      and cortisol in ewes during suckling and machine milking.
AB  - Milk yield and plasma oxytocin (OT), prolactin (PRL), and cortisol (CORT) during
      suckling and machine milking were measured in multiparous ewes subjected to a
      mixed management system of 3 sucklings and two daily milkings. Peak hormones were
      significantly increased and were similar during suckling and milking for PRL (181
      vs. 163.3 ng x mL(-1)) and CORT (12.5 vs. 11.5 ng x mL(-1)). During the period of
      exclusive suckling, OT was always significantly released (90.3 pg x mL(-1));
      however, during the period of mixed management, OT concentrations only increased
      during suckling compared to milking (91.7 vs. 13.1 pg x mL(-1)). The mean volume
      of milk obtained during suckling (632 mL) was significantly higher than during
      milking (255 mL). Thus, during a mixed management system, oxytocin and prolactin
      releases are not under similar central regulation. A mixed system, without OT
      release during milking, does not contribute to accelerate the conditioning of
      ewes for machine milking.

PMID- 10943607
TI  - A biphasic action of estradiol on estrogen and progesterone receptor expression
      in the lamb uterus.
AB  - Regulation of the uterine expression of estrogen and progesterone receptors was
      studied in 20 three-month-old lambs that were not treated or treated with
      estradiol- 17beta. Determinations of receptors were performed by binding assays
      in the nuclear and cytosolic fractions, receptor mRNAs by solution hybridization,
      and estrogen receptor protein by an enzyme-immunoassay. Estradiol treatment
      decreased the receptor binding capacity of both receptors and the levels of
      immunoreactive estrogen receptor 12 h after injection in the absence of decreased
      receptor mRNAs, suggesting that the initial decrease is due to degradation of the
      proteins or that mRNAs are translated into new receptor proteins at a reduced
      rate. The mRNA levels increased after estradiol treatment suggesting that the
      replenishment phase consists of synthesis of new receptors rather than recycling
      of inactivated receptors.

PMID- 10943608
TI  - Fraction of proliferating cells in granulosa during terminal follicular
      development in high and low prolific sheep breeds.
AB  - During terminal development of antral follicles, granulosa cells progressively
      lose their proliferative activity. Romanov (ovulation rate = 3) and Ile-de-France
      (ovulation rate = 1) breeds of sheep were compared for fractions of proliferating
      granulosa cells, determined by in vitro continuous [3H] thymidine labelling. In
      both breeds, the fraction of proliferating cells decreased with increasing
      follicular size according to a sigmoid-shaped curve. After linearization, the
      slope of the regression line was higher (in absolute value) in Romanov, compared
      to Ile-de-France ewes (p = 0.02). In vivo FSH treatment led to a decrease in the
      slope of the regression line in Romanov ewes only (p = 0.03). These results
      suggest that during terminal follicular development (1) the rate of cell cycle
      exit is higher in granulosa cells of Romanov, compared to lie-de-France
      follicles, and (2) Romanov granulosa cells are more responsive to exogenous FSH
      in term of proliferation. These mechanisms may underlie differential dynamics of
      follicular development in poly- and mono-ovulating breeds of sheep.

PMID- 10943609
TI  - Culture of porcine spermatogonia: effects of purification of the germ cells,
      extracellular matrix and fetal calf serum on their survival and multiplication.
AB  - Initial studies to establish an in vitro system allowing survival and
      multiplication of porcine spermatogonia are described. Purified spermatogonia
      from 3-week-old pigs were cultured for 9 days alone or in the presence of Sertoli
      cells in either control medium or in medium supplemented with 5%, fetal calf
      serum (FCS). Under either condition the number and the viability of the cells
      decreased with time. but both parameters were positively influenced by the
      presence of FCS. However, very few, if any, spermatogonia were able to take up
      BrdU under either condition. In another series of experiments, small fragments of
      seminiferous tubules from 3-week-old pigs were cultured in the presence of FCS,
      or seeded on an extracellular matrix. Under these conditions the number of cells
      decreased between day 0 and day 2 or day 5, then it remained roughly constant
      until the end of the culture. The number of spermatogonia decreased 2.5 fold
      during the two-week culture period. Spermatogonia were able to incorporate BrdU
      until the end of the experiment. The number of BrdU-labeled spermatogonia was
      higher when tubule-segments were seeded on an extracellular matrix. Then, the
      effects of the association of FCS and extracellular matrix were tested. The
      number of spermatogonia, during the whole culture period, was higher in serum
      containing cultures than in serum-free cultures. As for the number of
      spermatogonia able to incorporate BrdU at -different days, is decreased 3 fold
      between day 2 and 14 irrespective of the culture conditions. By contrast, the
      number of spermatogonia, labeled with BrdU between day 1 and 2, measured on days
      5 to 14 of culture, was higher in serum-containing cultures. Finally, the number
      of spermatogonia labeled between day 1 and 2 was higher from day 5 onward than
      the number of spermatogonia able to take up BrdU between days 4 and 13. Taken
      together, these results indicate that intercellular communication and
      extracellular matrix are important for spermatogonia multiplication and that FCS
      promotes the survival of spermatogonia under in vitro conditions.

PMID- 10943610
TI  - Improved survival of idiopathic dilated cardiomyopathy in the 1990s.
AB  - To analyze the recent change in the long-term survival of patients with dilated
      cardiomyopathy (DCM), the present study comprised consecutive 111 patients with
      ejection fraction <50% and left ventricular end-diastolic diameter >58 mm. who
      were admitted to hospital from January 1983 to December 1994. The patients were
      divided into 2 groups: group A who were diagnosed before 1989 and group B
      diagnosed after 1990. Basic characteristics at diagnosis, including age, NYHA
      functional class, left ventricular end-diastolic diameter and ejection fraction,
      were similar between these 2 groups. Calculated survival rate at 5 years was
      90.0% in group B in contrast to 62.3% in group A. Event-free survival also
      improved in group B. In group B, beta-blockers and angiotensin converting enzyme
      inhibitors were more frequently used than in group A (p<0.0001) whereas digitalis
      and other positive inotropic agents were significantly less used. Left
      ventricular ejection fraction was significantly improved during the follow-up
      period in patients treated with beta-blockers compared with those not treated
      with beta-blockers. These data indicate a significant improvement in the survival
      of patients with dilated cardiomyopathy after 1990, which may be explained by the
      change of medical treatment, especially the use of beta-blockers.

PMID- 10943611
TI  - Neurally mediated syncope and arrhythmias: a study of syncopal patients using the
      head-up tilt test.
AB  - Understanding the causes of syncope in patients with arrhythmia is important in
      determining the therapeutic interventions. Neurally mediated syncope (NMS) was
      evaluated in 55 patients with various arrhythmias. The head-up tilt test with or
      without isoproterenol infusion induced NMS in 41 (74%) patients. When these
      patients was categorized into 3 types, depending on the development of syncope,
      vasodilatation was significant in a majority of patients. In 46% of patients with
      tachyarrythmias, NMS was accompanied by an increase in extrasystole. It was
      concluded that the evaluation of vasodilatation is important for the preventive
      strategy of NMS in patients with arrhythmias and that NMS may induce arrhythmias.

PMID- 10943612
TI  - Implications of marked fatty infiltration around and in the atrophic
      atrioventricular node in elderly patients with permanent pacemaker implantation
      for symptomatic sick sinus syndrome.
AB  - The present study undertook an extensive analysis of the histopathological
      findings of the atrioventricular conduction system in 14 elderly patients treated
      with permanent pacemakers for sick sinus syndrome (SSS). Special attention was
      given to the lowest Wenckebach block points of atrioventricular conduction during
      rapid atrial pacing, and ventricular rate or duration of ventricular pause during
      chronic atrial fibrillation. An electrophysiological study (EPS) was conducted
      under sinus rhythm in 13 patients and under junctional escape rhythm in 1
      patient. Three of the 14 cases showed a lower Wenckebach block point of 130
      beats/min or less. Two of these 3 cases showed excessive fatty infiltration
      around the atrionodal junction area and into the atrophic atrioventricular node
      (AVN) itself. Of the 6 patients who had chronic atrial fibrillation after
      pacemaker implantation, 2 cases showed a slow ventricular response of less than
      60 beats/min and/or a long ventricular pause of 3.3 s. One of the 2 cases showed
      a lower Wenckebach block point of 130 beats/min at the time of EPS. The other,
      who later progressed to idiopathic atriomegaly, also showed marked fatty
      infiltration around the AVN. This fatty lesion was closely associated with
      diffuse disruption of the muscular fibers connecting the atrophic AVN with the
      atrium. In addition, most of the remaining cases also had an atrophic AVN. In
      conclusion, a sparse or absent atrionodal connection and an atrophic AVN due to
      excessive fatty infiltration in the atrionodal transitional area should be
      investigated in atrioventricular conduction disturbances in the elderly with SSS.

PMID- 10943613
TI  - Abnormal coronary flow profiles at rest and during rapid atrial pacing in
      patients with hypertrophic cardiomyopathy.
AB  - To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy
      (HCM), coronary flow velocity was measured in the left anterior descending
      coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8
      normal controls. The average peak velocity (APV), percent increase of APV (%APV),
      and APV during systole (Vs) and diastole (Vd) were calculated at rest and during
      rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90
      beats/min, while in the controls the APV increased continuously until the heart
      rate reached 130 beats/min [%APV (130 beats/min); 103+/-30% in HCM vs 139+/-23%
      in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased,
      whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a
      peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased
      continuously until the heart rate reached 130 beats/min. The acceleration rate of
      early diastolic flow was significantly lower in HCM than in the controls (1.85+/
      0.66 vs 3.18+/-1.62 m/s2, p<0.03). This abnormal response might be due to an
      increase in the reverse systolic flow and a decrease in the diastolic flow,
      probably caused by a slow acceleration of early diastolic flow velocity in the
      LAD.

PMID- 10943614
TI  - Elevated circulating levels of basic fibroblast growth factor and vascular
      endothelial growth factor in patients with acute myocardial infarction.
AB  - Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor
      (VEGF) have both shown strong angiogenetic effects in ischemic animal models and
      it has been reported that these growth factors were increased after acute
      myocardial ischemia. However, there have been few reports on the serum levels of
      bFGF and VEGF after acute myocardial infarction (AMI), in particular there has
      not been a comparative study of bFGF and VEGF in human subjects. The time course
      of circulating levels of bFGF and VEGF was examined in 36 patients with AMI who
      were within 24h of the onset of the AMI. The serum bFGF and VEGF levels of 50 age
      and sex-matched healthy volunteers served as the baseline value. All the
      patients had undergone coronary angiography on the day of admission (Day 0), but
      prior to that the serum bFGF and VEGF levels were examined by enzyme-linked
      immunoassay. The serum bFGF and VEGF levels were also evaluated on Days 7, 14 and
      28. Creatine kinase, myosin light chain I and troponin-T were measured
      subsequently and radionuclide examinations were performed during the early phase
      of AMI to determine the infarct size. The serum bFGF levels were significantly
      increased at Day 0 and were maintained until Days 7 and 14. Although serum VEGF
      levels at Day 0 were similar to the baseline values, they showed a remarkable
      increase by Days 7 and 14. A high serum level of bFGF was detected in the acute
      phase of AMI, and a later increase in VEGF was determined in the sub-acute phase,
      which suggest that these 2 growth factors play an important role at different
      time points of the reconstructing process of infarcted myocardial tissue.

PMID- 10943615
TI  - Role of cytokines and adhesion molecules in ischemia and reperfusion in patients
      with acute myocardial infarction.
AB  - Although acute myocardial infarction (AMI) may involve both plaque rupture and
      ischemia-reperfusion injury, the pathogenesis of these phenomena is unclear. To
      elucidate the pathogenesis of AMI, serial measurements of platelet activating
      factor (PAF), interleukin-6 and cell adhesion molecules were made in patients
      with AMI. The PAF levels were measured upon hospital admission and at 24 and 72h
      in 8 patients with AMI. Serum levels of interleukin-6, soluble E-selectin (sE
      selectin), soluble intercellular adhesion molecule-1 and soluble vascular cell
      adhesion molecule- 1 (sVCAM- 1) were measured upon admission and at 24 h and 4
      weeks in 30 patients with AMI and 15 patients with stable effort angina. PAF
      levels were higher in patients with AMI than in normal volunteers; the increased
      levels lasting at least 72h. In contrast, interleukin-6 increased at 24h. sE
      selectin was elevated at admission and sVCAM-1 increased later. sE-selectin
      levels upon admission in patients with additional ST-segment elevation after
      reperfusion were significantly higher than those in patients without ST
      elevation. In patients with AMI, the time-course of changes in blood levels of
      cytokines varied according to the individual substances. Although it is unclear
      what is the precise role of each of the cytokines in the pathophysiology of AMI,
      sE-selectin may be possibly related to the reperfusion injury in the infarcted
      myocardium.

PMID- 10943616
TI  - Alterations in sarcoplasmic reticulum and angiotensin II receptor type 1 gene
      expression in spontaneously hypertensive rat hearts.
AB  - Left ventricular hypertrophy (LVH) is an adaptive change in response to
      hypertensive pressure overload. Some evidence indicates that the decrease in
      sarcoplasmic reticulum (SR) Ca2+-ATPase mRNA expression, which may contribute to
      a diastolic dysfunction of the heart, occurs in the experimental pressure
      overload model. Also, recent studies have demonstrated that angiotensin II (Ang
      II) and angiotensin II receptor type 1 (AT1) play important roles in LVH. The
      purpose of this study was to investigate the function of the SR and the role of
      AT1 in genetic hypertension in spontaneously hypertensive rats (SHR) at ages 10
      and 18 weeks. In SHR, cardiac hypertrophy has already developed at 10 weeks of
      age. SR Ca2+-ATPase activity and mRNA expression were significantly lower in SHR
      than in Wistar-Kyoto rats (WKY). Plasma renin activity in SHR was unchanged
      compared with WKY, whereas the Ang II concentration in SHR was significantly
      higher than that in WKY. AT1 mRNA expression in SHR was similar to that in WKY.
      These results suggest that in the early stage of hypertension in SHR Ang II may
      stimulate hypertrophy in the cardiomyocytes through the AT1, which is not
      downregulated by a high concentration of Ang II.

PMID- 10943617
TI  - Generation of free radicals and the damage done to the sarcoplasmic reticulum
      during reperfusion injury following brief ischemia in the canine heart.
AB  - Free radical generation was studied by the electron spin resonance (ESR)
      technique using alpha-phenyl N tert butyl nitrone (PBN) in a brief ischemia
      reperfusion model of the canine heart, and correlated with biochemical changes of
      the sarcoplasmic reticulum (SR). ESR spectra (aH=0.3-0.4mT, aN=1.43-1.58mT) were
      observed as PBN spin adducts, which peaked at levels 5-fold above the control
      levels at 5 min after reperfusion. The simulated coupling constants of PBN spin
      adducts suggested that the sample should contain at least 2 carbon-centered
      radicals at 5 min after reperfusion (radical A: aH=0.350mT, aN=1.485mT; radical
      B: aH=0.370mT, aN=1.615 mT). At this time point, a significant reduction in Ca
      ATPase activity of the SR was found without degradation of the major ATPase
      protein. Superoxide dismutase (SOD) significantly reduced the intensity of the
      PBN spin adduct signals and preserved the Ca-ATPase activity of the SR to 80% of
      the control level. Reperfusion injury after brief ischemia may be the result of
      inactivation of intracellular Ca-ATPase by free radicals generated during
      reperfusion, and SOD contributes to the protective effect by scavenging the
      radicals.

PMID- 10943618
TI  - Fluorescence spectrum analysis of atherosclerotic plaque using doxycycline.
AB  - Using doxycycline (DOXY), fluorescence spectrum analysis was performed on
      arteriosclerotic lesions, and the efficacy of this method was examined in basic
      and clinical studies. In the basic study, DOXY 50 mg was administered
      intravenously to arteriosclerotic rabbits, and the thoracoabdominal aorta
      removed. Fluorescence spectral analysis was performed on each specimen, and the
      fluorescence spectral pattern, peak intensity and degree of intimal hypertrophy
      were studied. In the clinical study, DOXY 200 mg was administered intravenously
      to 6 human subjects with stable angina and coronary arterial stenosis of greater
      than 90%, and coronary angiography, coronary angioscopy and fluorescence spectral
      analysis were performed. DOXY accumulation in the arteriosclerotic intima of
      rabbit aortae was confirmed. The fluorescence spectrum was monomodal, peaking at
      around 532 nm. In the noncalcification group, significant correlation was
      observed between peak intensity and arteriosclerotic intimal thickness. Using
      DOXY as a fluorescent marker, it was possible to assess the level of
      arteriosclerotic intimal hypertrophy. Clinically, it was possible to obtain the
      DOXY spectrum of the coronary arteries.

PMID- 10943619
TI  - Photodynamic therapy for the prevention of intimal hyperplasia in balloon-injured
      rabbit arteries.
AB  - This study was performed to demonstrate accumulation of the photosensitizer
      hematoporphyrin derivative (HPD) in atherosclerosis and to determine whether
      intimal hyperplasia, the main cause of restenosis after angioplasty, can be
      inhibited by photodynamic therapy (PDT). Forty Japanese White rabbits were
      subjected to balloon endothelial injury in the common iliac artery. Five groups
      of rabbits, ie, immediately after, or 3, 7, 14 or 28 days after the balloon
      injury, were injected with HPD. These rabbits were sacrificed 24h after HPD
      administration, and HPD fluorescence was investigated in the injured arteries by
      fluorescence microscopy. Other groups of rabbits were injected with HPD 24h
      before PDT, and they were then subjected to intravascular Hg-Xe flash-lamp
      irradiation immediately after (0D-PDT), or 3 days (3D-PDT), 7 days (7D-PDT), or
      14 days (14D-PDT) after the balloon injury. All rabbits were sacrificed 28 days
      after the balloon injury, and histological sections of PDT-treated arteries were
      examined by light microscopy. Slight, uniform HPD accumulation was observed in
      the injured media immediately after the balloon injury, and throughout the entire
      media and the neointima on day 7. On day 14, HPD accumulation had diminished in
      the media and increased in the intima, and on day 28 no HPD remained in the
      media. In the 0D- or 3D-PDT groups, no inhibition of intimal hyperplasia was
      observed. In contrast, there was significant inhibition of intimal hyperplasia in
      the 7D- and 14D-PDT groups, and the most effective inhibition was in the 7D-PDT
      group. This study demonstrated that PDT with HPD inhibits smooth muscle cell
      growth and decreases the intimal hyperplasia response in rabbits.

PMID- 10943620
TI  - Mitral valve thrombus attached to the intact mitral valve associated with distal
      embolism.
AB  - A 61-year-old man was referred for cardiac investigation because embolism was
      suspected to be the cause of the sudden onset of severe pain in his right leg
      after a surgical procedure. The electrocardiogram revealed no atrial
      fibrillation. Transthoracic echocardiography demonstrated a tumor-like echo at
      the anterior mitral leaflet, and transesophageal echocardiography documented a
      mass 13x9mm in size, attached by a stalk to the left atrial side of the anterior
      mitral leaflet. The other parts of the mitral valve appeared to be intact. At
      emergency surgery, the mass was located in the center of the left atrial side of
      the anterior mitral leaflet. It mimicked a myxoma and had a stalk arising from
      the anterior leaflet. After resection of the mitral valve mass, catheter thrombo
      embolectomy was performed and several long pieces of fresh thrombus were removed.
      On histological examination, the mass consisted of fresh thrombus tissue. No
      cellular component or myxoma tissue was documented. The distal embolus also
      consisted of fresh thrombus tissue. This is the first case of a thrombus of the
      intact mitral valve without atrial fibrillation.

PMID- 10943621
TI  - Left ventricular free wall rupture in acute fulminant myocarditis during long
      term cardiopulmonary support.
AB  - A 77-year-old woman with acute myocarditis developed cardiogenic shock soon after
      admission and was given mechanical cardiopulmonary support. Echocardiography
      revealed severe global left ventricular hypokinesia. After 5 days of mechanical
      support, left ventricular wall motion gradually began to improve, but the patient
      died of cardiac tamponade on day 13. At necropsy, a free wall rupture was found
      where the apical akinetic area bordered the basal portion, an area which had
      shown better wall motion. Left ventricular free wall rupture in acute myocarditis
      has not been reported, but this case indicates that it may occur in fulminant
      myocarditis when a cardiopulmonary support system is used.

PMID- 10943622
TI  - Hemolytic anemia in native valve infective endocarditis: a case report and
      literature review.
AB  - Hemolytic anemia is a rare manifestation of infective endocarditis. A 19-year-old
      man with a small ventricular septal defect developed right-sided infective
      endocarditis with huge vegetations involving the tricuspid valve, the ventricular
      septal defect, and the pulmonary valve. Intravascular hemolysis was suggested by
      the presence of numerous fragmented erythrocytes, giant platelets and
      polychromasia of the red blood cells. The direct Coombs test was positive, and
      there were spherocytes and splenomegaly, findings that suggested an immune
      mediated mechanism also played a role in the hemolysis. The hematological picture
      persisted despite antibiotic therapy and recovered only after surgical removal of
      the vegetations, tricuspid and pulmonary valvectomy, and patch closure of the
      ventricular septal defect.

PMID- 10943623
TI  - Ventriculoatrial shortening achieved in Wolff-Parkinson-White syndrome by
      programmed right ventricular pacing.
AB  - A 47-year-old woman with a left-sided Kent bundle showed marked reduction of the
      ventriculoatrial conduction time during extrastimuli at the right ventricular
      apex and outflow tract. The degree of reduction was greater than 6 years ago. A
      'supernormal conduction' in the ventricle and the Kent bundle could have been
      responsible for this phenomenon.

PMID- 10943624
TI  - Improvement of regional myocardial and coronary blood flow reserve in a patient
      treated with enhanced external counterpulsation: evaluation by nitrogen-13
      ammonia PET.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive treatment for chronic
      stable angina, which works by recruiting and developing the coronary collateral
      vessels. Coronary perfusion and coronary flow reserve (CFR) were evaluated by
      nitrogen-13 (13N) ammonia positron emission tomography (PET) in a patient who had
      undergone EECP. The patient, who had 3-vessel coronary artery disease, required a
      percutaneous transluminal coronary angioplasty (PTCA) for the right coronary
      artery. The PTCA was successful, but 6 months later he again felt chest
      oppression. The coronary angiography showed re-stenosis at the PTCA site, and
      other progressive coronary stenosis. The patient was again treated with EECP for
      35 h. The 13N-ammonia PET was performed both at baseline and during dipyridamole
      provocation, before and after EECP treatment. Coronary perfusion of each
      myocardial wall increased at the baseline (anterior: 0.52-0.75; septal: 0.48
      0.66; lateral: 0.61-0.68; inferior: 0.46-0.57 ml min(-1) g(-1), and the CFRs in
      the septal and inferior walls (septal: 2.07-2.15; inferior: 1.99-2.06) also
      increased after the treatment. Thus, the EECP treatment improved both coronary
      perfusion at baseline and CFR, which suggests that it may be one of the choices
      for treatment of angina.

PMID- 10943625
TI  - Two-stage repair for aortic regurgitation complicated by severe coarctation of
      the thoracoabdominal aorta due to Takayasu's arteritis.
AB  - Takayasu's arteritis is a rare inflammatory aortoarteritis of unknown etiology
      and causes stenoocclusive disease of the aorta and its branches as well as aortic
      regurgitation. A surgical case of Takayasu's arteritis is presented. A 56-year
      old female exhibited aortic regurgitation complicated by severe coarctation of
      the thoracoabdominal aorta due to Takayasu's arteritis. In this case, a 2-staged
      repair, consisting of an axillofemoral bypass and an aortic valve replacement,
      was successfully performed.

PMID- 10943626
TI  - Primary leiomyosarcoma of the left atrium.
AB  - A 69-year-old woman with symptoms of congestive heart failure had a left atrial
      leiomyosarcoma, an extremely rare cardiac tumor, which obstructed the mitral
      valve and pulmonary veins. Surgical resection was performed, but no other
      adjuvant therapy was administered because the patient refused it. Recurrence of
      the tumor occurred soon after surgery and the patient died 81 days
      postoperatively.

PMID- 10943627
TI  - Uncommon atrial flutter originating in the left atrioventricular groove:
      emergence after successful catheter ablation for a left concealed accessory
      pathway.
AB  - This report describes a 49-year-old male with concealed Wolff-Parkinson-White
      syndrome in whom a true uncommon atrial flutter suddenly emerged 2 weeks after
      successful catheter ablation of a left-sided accessory pathway. The earliest
      atrial activation during the atrial flutter was recorded at the posterolateral
      mitral annulus 2 cm proximal to the previous successful ablation site for the
      accessory pathway. Two applications of radiofrequency (RF) current directed at
      the supravalvular mitral annulus could not terminate the atrial flutter. A
      subsequent delivery of RF current directed at the subvalvular annulus, where a
      local fragmented potential preceded the earliest atrial activation, eliminated
      the atrial flutter.

PMID- 10943628
TI  - Clarithromycin associated with torsades de pointes.
AB  - Two cases of QT prolongation and torsades de pointes (TdP) are presented. The
      patients had been taking clarithromycin (400 mg/day) for respiratory disease.
      Although erythromycin is reportedly associated with TdP, this is the first report
      of clarithromycin associated with TdP in the absence of other drugs already known
      to produce QT prolongation.

PMID- 10943629
TI  - Coronary artery bypass grafting in a patient with human immunodeficiency virus:
      role of perioperative active anti-retroviral therapy.
AB  - In a patient with severe ischemic heart disease and advanced human
      immunodeficiency virus (HIV) infection, vigorous perioperative treatment with
      anti-retroviral agents was given and coronary artery bypass surgery using
      cardiopulmonary bypass was successfully performed. This strategy could become the
      standard for patients with cardiovascular disease and advanced HIV infection. The
      following aspects of this case require further investigation: (1) lack of a
      reactive increase in the neutrophil count, (2) transient extreme reduction of
      lymphocytes, and (3) a relative decrease in the CD8+ cell ratio.

PMID- 10943630
TI  - Familial atrial septal defect and atrioventricular conduction disturbance
      associated with a point mutation in the cardiac homeobox gene CSX/NKX2-5 in a
      Japanese patient.
AB  - Atrial septal defect (ASD) is the most common form of congenital cardiac defect
      in humans. Recently, point mutations in the cardiac homeobox gene CSX/NKX2-5 have
      been reported to cause the autosomal dominant form of familial ASD. Notably, all
      the affected patients exhibit atrioventricular conduction disturbance and some of
      them died suddenly. The first case of familial ASD with a mutation of the
      CSX/NKX2-5 gene in a Japanese patient is reported here. Identification of
      CSX/NKX2-5 mutations in ASD patients would be very important because the
      existence of such mutations may predict sudden cardiac death.

PMID- 10943632
TI  - Allergen immunotherapy: does it work and, if so, how and for how long?

PMID- 10943631
TI  - Family size, infection and atopy: the first decade of the "hygiene hypothesis".

PMID- 10943634
TI  - Oral corticosteroids for exacerbations of chronic obstructive pulmonary disease.

PMID- 10943633
TI  - Prophylaxis of Pneumocystis carinii pneumonia: too much of a good thing?

PMID- 10943635
TI  - Smoking cessation.

PMID- 10943636
TI  - Traveller's thrombosis.

PMID- 10943637
TI  - Interferon gamma-1b therapy for cryptogenic fibrosing alveolitis.

PMID- 10943638
TI  - Obesity, respiratory function and breathlessness.

PMID- 10943639
TI  - New developments in the treatment of obstructive sleep apnoea.

PMID- 10943640
TI  - Inhaled nitric oxide treatment for preterm infants with hypoxic respiratory
      failure.

PMID- 10943641
TI  - Detection of early lung cancer.

PMID- 10943642
TI  - Management of febrile neutropenia in low risk cancer patients.

PMID- 10943643
TI  - Outcome measures in asthma.

PMID- 10943644
TI  - Vegan diet in physiological health promotion.
AB  - We have performed a number of studies including dietary interventions and cross
      sectional studies on subjects consuming uncooked vegan food called living food
      (LF) and clarified the changes in several parameters related to health risk
      factors. LF consists of germinated seeds, cereals, sprouts, vegetables, fruits,
      berries and nuts. Some items are fermented and contain a lot of lactobacilli. The
      diet is rich in fiber. It has very little sodium, and it contains no cholesterol.
      Food items like berries and wheat grass juice are rich in antioxidants such as
      carotenoids and flavonoids. The subjects eating living food show increased levels
      of carotenoids and vitamins C and E and lowered cholesterol concentration in
      their sera. Urinary excretion of sodium is only a fraction of the omnivorous
      controls. Also urinary output of phenol and p-cresol is lowered as are several
      fecal enzyme levels which are considered harmful. The rheumatoid arthritis
      patients eating the LF diet reported amelioration of their pain, swelling of
      joints and morning stiffness which all got worse after finishing LF diet. The
      composite indices of objective measures showed also improvement of the rheumatoid
      arthritis patients during the intervention. The fibromyalgic subjects eating LF
      lost weight compared to their omnivorous controls. The results on their joint
      stiffness and pain (visual analogue scale), on their quality of sleep, on health
      assessment questionnaire and on general health questionnaire all improved. It
      appears that the adoption of vegan diet exemplified by the living food leads to a
      lessening of several health risk factors to cardiovascular diseases and cancer.
      Rheumatoid patients subjectively benefited from the vegan diet which was also
      seen in serum parameters and fecal analyses.

PMID- 10943645
TI  - Vitality diagnostics and preventive medicine for the well-being of people at
      advanced age.
AB  - This paper emphasises the importance of vitality diagnostics in relation to
      healthy ageing and prevention of age-associated diseases. Ageing, reducing the
      reserve capacity, decreases the adaptability of various systems and increases the
      risk of functional disorders. The early recognition and treatment of functional
      disorders in vitality diagnostics laboratories provides an opportunity to prevent
      or delay the onset of degenerative diseases related to advanced age.

PMID- 10943647
TI  - Behavioural medicine in health promotion.
AB  - Behavioural medicine is a rapidly developing interdisciplinary field that
      integrates the physiological and psychosocial aspects of human behaviour and
      applies them to prevention. In the early stage of chronic non-infectious
      illnesses of great epidemiological significance the most important risk factors
      are the reversible psychophysiological regulation disturbances. According to the
      behavioural medicine model depressive symptomatology, hopelessness, anxiety, non
      adaptive ways of coping, dysfunctional attitudes are common risk factors in the
      background of self-destructive behavioural disturbances, such as smoking, alcohol
      and drug abuse and suicidal behaviour. The basic link between physiological and
      psychological phenomena is the decision making process, the cognitive appraisal,
      evaluation of the given situation, which is very subjective and depends on the
      socialization process. The modern civilised way of life continuously creates
      situations in which we experience loss of control, and therefore the
      psychological and physiological balance can only be obtained with great
      difficulty. Especially under conditions of sudden cultural and socioeconomic
      transition strengthening adaptive ways of coping and preventing emotional
      disturbances are fundamental in health promotion.

PMID- 10943646
TI  - Atherosclerosis risk factors in children of high risk families.
AB  - The Objective of this study was to determine the frequency of care reactive
      atherosclerosis risk factors in children of parents with premature coronary heart
      disease observed before their 45 years of age for the promotion of the
      effectivity of the preventive work started in childhood and adolescent ages.
      METHODS: Height and weight was measured. Body mass index (BMI) was calculated.
      Fat analysis was performed in children with overweight. Blood pressure was
      measured and both 24 hour monitoring and fundoscopy were performed in cases with
      a blood pressure higher than 90 centile values. Fasting blood sugar (BS) level
      was measured. Oral glucose tolerance test was made in cases with a fasting BS
      level higher than 5 mmol/l. Serum total cholesterol (TC), HDL-cholesterol (HDLC)
      and total triglyceride (TT) levels were measured and LDL-cholesterol (LDLC) level
      was calculated. The plasma thiobarbituric acid reactive system (TBARS) was
      investigated. Statistical analyses were performed by chi2 and Student t-probes.
      Data of 1140 offsprings and 457 referents without any high atherosclerotic risk
      family history were analyzed. RESULTS: BMI of 87 offsprings was higher than the
      90 centile value. The fat percent of the body of these children was higher than
      40. The blood pressure of 311 children and adolescents was higher than the 90
      centile value. Fasting BS level was higher than 5 mmol/l in 47 cases 17 of them
      showed a pathologic oral glucose tolerance test. High serum TC level was observed
      in 67 cases, high serum TT level was found in 8 cases. 245 offsprings had a low
      serum HDLC level. The plasma TBARS level was high in 241 cases. Data of referents
      differed significantly from those of offsprings. Their serum TC, LDLC levels and
      plasma TBARS level were lower, serum HDLC level was higher than that of children
      and adolescents with high risk atherosclerotic family history. CONCLUSION: Risk
      factors of atherosclerosis are detectable in children and adolescents of high
      risk families. The measurement of these factors may help the efficacy of the
      preventive work.

PMID- 10943648
TI  - Is it reasonable to involve kinesiology in medical education?
AB  - The purpose of this study is to argue for teaching kinesiology for medical
      students. To become familiar with the basics of the science of human motions is
      essential for the medical practice. There is substantial evidence that regular
      physical exercise is beneficial to improve health and prevent disease, and has a
      key place among the strategies in therapy and rehabilitation. However, before
      prescription of exercise programmes the physician must take into consideration
      all the benefits and risks of that exercise. The present curriculum offers
      insufficient information about the physiological effects and physiologically
      essential limits of physical exercise. Therefore, a regular study of human
      motions is required by the medical practice. The need for such education is also
      shown by the everlasting interest of medical students in credit courses of
      kinesiology and sports physiology.

PMID- 10943649
TI  - The way teaching human physiology can support primary prevention.
AB  - In this article, a rationale is provided to prove that teaching human physiology-
      according to its definition and characteristics--could effectively support also
      the cause of health culture and prevention by establishing an appropriate, high
      level scientific background knowledge in the medical schools. The concept of a
      reform curriculum of integrative physiology developed in order to serve this task
      is outlined. An international cooperation is suggested to develop further this
      concept.

PMID- 10943650
TI  - An approach to primary prevention from the aspect of applied physiology.
AB  - The main reason for our decreasing population number--a most remarkable indicator
      of the inadequacy of our health culture--is the high rate of overall mortality.
      In its background one finds a number of risk factors of high prevalence, such as
      hypertension disease, addiction pathology, reduced stress tolerance as well as
      physical and psychic inactivity. Patterns of life that are positive are scarce
      and as yet not attractive or efficient. The spirit of primary prevention is yet
      far from permeating medicine; the most the clinical side did realize has been a
      recognition of the population's need for regular medical screenings. A completely
      new approach that involves prevention programs embracing the whole of society,
      and an elaboration of new strategies are badly needed to achieve a desirable
      change in the present set of values. One of the already available remedies is to
      give full and science-based support to the positive life patterns in our culture,
      for instance by demonstrating how physiology can be applied to human life, by
      putting the latter within a broader scope, namely that of psychophysiology and
      social psychology. In this framework the elements to be discussed are such
      aspects of culture as dietary habits, physical exercise, and mental and sexual
      hygiene. Placing greater emphasis on sports and intense habitual physical
      exercise can promote a healthier lifestyle, above all in our youth.

PMID- 10943651
TI  - Central thermoregulatory effects of neuropeptide Y and orexin A in rats.
AB  - Orexin A and neuropeptide Y that are known to induce a feeding response when
      applied centrally, in the present studies also caused hypothermia. Neuropeptide Y
      elicited hypothermia by depressing metabolic rate (without affecting heat loss
      mechanisms), while orexin A acted through enhancing peripheral heat loss (without
      affecting metabolic rate). Neither peptide induced coordinated thermoregulatory
      changes, both of them appeared to influence thermoregulation via different
      effector mechanisms.

PMID- 10943652
TI  - The effect of detraining on echocardiographic parameters due to injury.
AB  - Regular exercise training modifies the morphological and functional properties as
      well as the autonomous regulation of the heart. Such changes constitute what is
      termed an athletic heart, and were found to be reversible so after a
      discontinuation of regular exercise cardiac parameters gradually return to the
      non-athletic values. As yet, however, it has not been fully settled 1) how long a
      period of detraining is necessary to elicit such reversion, and 2) whether the
      various characteristics of an athletic heart would move concurrently or the time
      course of their change is different. In order to get more insight, the
      echocardiographic correlates of these problems were studied in 22 female and 23
      male physical education students forced by an injury to discontinue their
      exercise for some time. A sex and age matched group of non-athletic subjects and
      data published about a group of elite athletes served as contrast. The studied
      resting parameters were the wall thickness and internal diameter of the left
      ventricle, left ventricular relative muscle mass, relative stroke volume and
      cardiac output, and heart rate. It was inferred that--in respect of the
      echographical parameters--the time taken until the first signs of detraining
      depended on the athlete's previously attained level of conditioning, and that
      there was a definite order of sequence in that functional changes preceded
      morphological ones.

PMID- 10943653
TI  - Characteristics influencing changes in aerobic performance of children aged 7-9.
AB  - Interpretation of the actual level of aerobic endurance in a growing child is
      difficult. Endurance capacity per se is influenced by a number of factors, e.g.
      by genetic endowment, developmental rate, body composition and habitual physical
      activity. The respective effects of these factors cannot be distinctly separated
      from one another, so their particular role is not clearly definable in the
      various age periods. The aim of our investigation was to define the actual level
      of aerobic endurance performance in children aged 7-9, and to analyse the
      relevant factors that may affect this kind of performance according to the
      different level of sport activities. Two primary school classes (N=42) were
      selected for the experiment. Both groups had physical education classes every day
      (five times a week). One group (AG, N=31) consisted of children taking part in
      regular sport courses at least twice a week (e.g. basket ball, karate, triathlon
      swimming and gymnastics), as well, the other group (NAG, N=11) served as
      comparison group. Aerobic performance was estimated by measuring
      cardiorespiratory response during a Jaeger treadmill run using a "vita maxima"
      (all-out) testing protocol. The subjects were measured in the Laboratory for
      Spiroergometry of the Hungarian University of Physical Education twice, in 1997
      and 1998. Body composition was assessed by the Drinkwater-Ross [4] body mass
      fractionation technique. Robustness of the body was described by using the
      plastic index (PLX) of Conrad's growth type [2], morphological age (MORF AGE) was
      estimated by using the method of Meszaros and Mohacsi [5]. Exercise performance
      was studied in the laboratory by using a Jaeger 6000 LE model treadmill and a
      Jaeger mu-DATASPIR model gas analyser. The functional status of the subjects'
      cardiopulmonary system was estimated by spiroergometric parameters and total
      mechanical work (WORK). The AG group had a better endurance performance in 1998
      than that of non-athletic group. A factor analytic study (principal component
      method) of the employed variables revealed that the higher level of endurance
      fitness in the athletic group was not only affected by growth in size, but also
      by an increased level of cardiorespiratory performance capacity.

PMID- 10943654
TI  - Exhaled carbon monoxide concentration increases after exercise in children with
      cystic fibrosis.
AB  - Oxidative stress and hypoxia, which may occur in cystic fibrosis patients (CF) at
      rest and may be worsened by exercise, induce the expression of heme oxygenase
      (HO)-1, resulting in increased carbon monoxide (CO) formation. We tested that
      exhaled CO level (eCO) was higher in CF patients than in healthy subjects, and
      that exercise increased CO production. Exhaled CO was measured electrochemically
      in 15 CF patients and 15 control subjects at rest (T0), immediately (T1) and 60
      minutes after a symptom-limited incremental bicycle exercise test (T60). Arterial
      oxygen saturation (TcO2) was monitored transcutaneously. Data are given as mean+/
      SEM. Baseline eCO was 1.90+/-0.26 ppm in the control and 1.93+/-0.27 ppm in the
      CF group. In both groups eCO was lower at T1 than at rest. In the control group
      eCO was also low at T60, but in the CF group it was increased compared to
      baseline level at this timepoint. Exercise caused oxyhemoglobin desaturation in
      CF patients which was related to the increase in eCO measured at T60 (r=0.67,
      p<0.01). Our findings suggest that exercise modulates the level of exhaled CO
      partly by worsening oxygenation in CF patients.

PMID- 10943655
TI  - Cold pressor test and retinal capillary perfusion in vasospastic subjects with
      and without capsular glaucoma (a preliminary study).
AB  - PURPOSE: Using the cold pressor test the authors investigated the change in
      retinal and neuroretinal capillary perfusion in vasospastic patients suffering
      from capsular glaucoma (CG) and in vasospastic control subjects. METHODS: Changes
      in retinal and optic nerve head capillary perfusion induced by the cold pressor
      test (one hand immersed in 4 degrees C water for 30 seconds, then in 30 degrees C
      water for 2 minutes) was measured using the Heidelberg Retina Flowmeter in 4
      patients with CG and in 5 healthy control subjects. Previously all subjects
      showed a reduction of cutaneous capillary flow higher than 70% in the cold
      pressor test (vasospastic reaction). One eye per subject was investigated. Two
      images were obtained for each phase (baseline, cold phase and warm phase), and
      the better quality image from each phase was selected for the measurements. One
      location on the temporal neuroretinal rim and one location on the temporal retina
      outside the peripapillary area were selected for the HRF measurements. RESULTS:
      In the CG group neuroretinal rim "Volume" decreased by 26.05%, "Flow" by 25.82%
      and "Velocity" by 23.91% (p<0.05), retinal "Volume" decreased by 12.30%
      (p=0.051), and retinal "Flow" by 22.36% (p=0.01) in the cold phase. All these
      parameters returned to the corresponding baseline values in the warm phase. In
      the control group a significant decrease was observed in retinal "Volume"
      (15.96%), "Flow" (17.81%), and "Velocity" (16.11%) in the cold phase (p<0.05),
      which diminished in the warm phase but remained still significant for "Flow" and
      "Velocity". CONCLUSION: Cutaneous cold provocation can induce an immediate
      decrease in retinal and optic nerve head capillary perfusion at least in a part
      of the vasospastic subjects with or without capsular glaucoma. This decrease
      diminishes or disappears quickly when the hand is immersed in warm water. To
      evaluate the potential role of cold-induced retinal and optic nerve head
      vasoconstriction in the pathogenesis of capsular glaucoma further investigations
      are necessary since this reaction was also present in the vasospastic control
      subjects.

PMID- 10943656
TI  - Application of an anti-HQIgY antibody for the measurement of IgY concentrations
      of hen's and quail's serum and yolk.
AB  - The development of a sensitive ELISA for the measurement of quail IgY (QIgY) was
      the main purpose of our study. The suitable antibody (AB) was prepared in
      rabbits. Both quail IgY (QIgY) and hen IgY (HIgY) were precipitated by this
      developed AB. For this reason it was marked as anti-hen-quail-IgY (a-HQIgY). The
      purified AB was conjugated with horseradish peroxidase (aHQIgY-HRP) and a
      sensitive direct ELISA was developed, based on this labeled AB. The prepared
      aHQIgY AB which was used in this developed ELISA method was suitable for the
      measurement of total and specific IgY concentration in domestic hen (Gallus
      domesticus) and Japanese quail (Coturnix coturnix japonica) either. As a result
      of our experiments it is very likely that there are identical sequences of IgYs
      of both species. This part of IgY has good antigen character at the same time.
      Probably, this phenomenon has occurrence in other Galliform species, too. Further
      investigations will be carried out in this field.

PMID- 10943657
TI  - Correlation of EEG asymmetry and hypnotic susceptibility.
AB  - Hypnosis research of the last decades confirmed that some cortical regions show
      characteristic modification of spontaneous brain electrical activity as a
      function of hypnotic responsiveness. Using FFT spectrum of 16 channel EEG
      recording, it was demonstrated that in highly susceptible subjects the right
      parieto-temporal region show more electric power than the left one while the low
      susceptibles have left side predominance or equilibrated power in all
      derivations. If a specific (Ericksonian) indirect hypnosis induction was
      administered, the same right side preponderance could be recorded in low
      susceptibles, too. On the basis of these results we can confirm the importance of
      the right parieto-temporal associative area in the alteration of consciousness
      characterizing hypnotic state.

PMID- 10943658
TI  - Validity of viscoelastic models of blood vessel wall.
AB  - Quantitative description of biomechanical behaviour of the blood vessel wall is
      needed for understanding normal and pathologic functions of the vascular system.
      In this study we investigated the stress relaxation of blood vessels. Strips were
      cut from the vessel wall and they were stretched in a stepwise manner until they
      tore. The mechanical stress (approximately 10(5)-10(6) Pa) induced in the strips
      was determined. This showed an initial steep rise and then a slow, near
      exponential decay (stress relaxation) after each step of stretch. For the
      mathematical description we used two technical models (the Maxwell and the Kelvin
      model--they are built of two elastic elements and of one viscous element), as
      well as a one-dimensional continuum mechanical model. The moduli of the models
      were identified with a curve fitting method. Our aim was to compare these models
      in order to elucidate, which one describes the rheological behaviour of the blood
      vessel more correctly. The results of our analysis show that the corresponding
      moduli diverge from each other in the Maxwell and Kelvin models: that is, they
      depend on the mode of the assumed connection between the mechanical units. In
      contrast, moduli of the continuous model are unambiguous. We conclude that the
      continuous model properly describes the stress relaxation of the vascular wall.
      Its advantage over the technical models is that moduli describing the
      viscoelastic behaviour of the tissue do not depend on the not wholly well-known
      structure of the wall components.

PMID- 10943659
TI  - Gender differences in the echocardiographic characteristics of the athletic
      heart.
AB  - Differences between males and females in the effects of regular physical training
      on the heart were investigated by echocardiography in 579 male (nonathletes: 122,
      athletes: 457) and in 336 (nonathletes: 84, athletes: 252) female subjects of
      variable age. The age groups were: children (<15 yr.), adolescent-young (15-18
      yr.), young adult (19-30 yr.), adult (31-45 yr.) and people elder than 45 yr
      older (45<). Hypertrophy characterised by relative left ventricular muscle mass
      (rel.LVMM) of the athletic heart was manifest also in the females, but in
      comparison with the males female values were much lower both in the unconditioned
      and in the conditioned groups. In people belonging to the oldest groups no
      differences were seen either between the males and females or between athletes
      and nonathletes. In comparing nonathletic subjects, females showed smaller left
      ventricular contractility as reflected by a higher LVET/QT ratio and an increased
      ability of diastolic relaxation as indicated by a higher E/A ratio. Physical
      training induced a more marked development when the initial level was lower,
      namely, in the contractility of the females, and in the compliance of the males.
      No intersex difference was seen in the modified regulation of the athletic heart,
      characterised by a lower resting heart rate and slower circumferential shortening
      velocity (VCF).

PMID- 10943660
TI  - Galanin mediated inhibitory nervous modulation of cutaneous vascular reactions.
AB  - Noxious stimulation induces local inflammatory responses in a variety of mammals
      but these reactions are only faint in avian species. The possibility that
      endogenous galanin inhibits neurogenic vascular responses in avians was tested in
      the wing skin of anaesthetized pigeons. Intraarterial infusion of nanomolar
      concentrations of the specific galanin antagonist M35 dose dependently enhanced
      the small mustard oil induced increase of skin blood flow measured by means of a
      Laser Doppler Imager. Similarly, the small transient vasodilatation following
      electrical stimulation of a cutaneous nerve was also enhanced by M35. The effect
      of M35 was not observed after chronic denervation. Coperfusion of M35 dose
      dependently augmented the histamine and bradykinin induced plasma extravasation
      revealed by skin microdialyses, but this effect was abolished in the chronically
      denervated skin. However, chronic denervation per se enhanced the plasma
      extravasation induced by histamine but not by bradykinin and this effect was
      diminished by coperfusion of galanin. The results suggest an inhibitory
      modulation of cutaneous neurogenic inflammatory reactions by endogenous galanin
      in the pigeon.

PMID- 10943661
TI  - Hyperphagia in cold-adapted rats: a possible role for neuropeptide Y.
AB  - The feeding response to intracerebroventricular injection of neuropeptide Y or to
      starvation is greater in cold-adapted than in non-adapted rats, suggesting that
      with cold-adaptation the central sensitivity to this peptide is increased.
      Hypometabolism and hypothermia (which usually follow the administration of
      neuropeptide Y) cannot, however, be demonstrated in the course of cold-adaptation
      per se.

PMID- 10943662
TI  - Exercise-physiological approach in the analysis of blood glucose curves.
AB  - The effect of a single bout of oral glucose administration on the blood glucose
      level during three hours of observation was studied at rest in 6 physical
      education students and in 6 elite walkers with different physical condition. The
      influence of the physical condition on the observed data was also investigated.
      The evaluation of the glucose tolerance test (OGTT) was first built on a
      mathematical model and it was developed by a new method. The point of the brand
      new method is the interrelationship between the relative percentage differences
      of blood glucose values, which is analysed as a function of time. The data of the
      new method better reflect the alterations of blood glucose regulation after oral
      administration of glucose. The new method contributes to the more accurate
      analysis of OGTT curves for beside estimation of the absolute values, it
      considers the relative differences, thus a thorough examination of the glucose
      metabolism can be carried out. It opens new potentialities in the analysis of the
      individual, absorptive, hormonal and fitness-dependent effects of different
      carbohydrates that are used abundantly by athletes.

PMID- 10943663
TI  - RNA shape space topology.
AB  - The distinction between continuous and discontinuous transitions is a long
      standing problem in the theory of evolution. Because continuity is a topological
      property, we present a formalism that treats the space of phenotypes as a
      (finite) topological space, with a topology that is derived from the
      probabilities with which one phenotype is accessible from another through changes
      at the genotypic level. The shape space of RNA secondary structures is used to
      illustrate this approach. We show that evolutionary trajectories are continuous
      if and only if they follow connected paths in phenotype space.

PMID- 10943664
TI  - Asymmetry of configuration space induced by unequal crossover: implications for a
      mathematical theory of evolutionary innovation.
AB  - Evolution can be regarded as the exploration of genetic or morphological state
      space by populations. In traditional models of population and quantitative
      genetics, the state space can be formally represented as a configuration space
      with clearly defined concepts of neighborhood and distance, defined by the action
      of variational operators such as mutation and/or recombination. In this paper, we
      describe a process where no genetic configuration space closure (and hence, no
      non-arbitrary notion of distance and neighborhood) exists. The process is gene
      duplication by means of unequal crossover, which we regard as an example of an
      "innovation" process that changes the state space of the system rather than
      exploring a closed state space. We assert that such processes are qualitatively
      distinct from representations of the adaptation process, which occur on regular
      configuration spaces.

PMID- 10943665
TI  - The evolution and understanding of hierarchical complexity in biology from an
      algebraic perspective.
AB  - We develop the rigorous notion of a model for understanding state transition
      systems by hierarchical coordinate systems. Using this we motivate an algebraic
      definition of the complexity of biological systems, comparing it to other
      candidates such as genome size and number of cell types. We show that our
      complexity measure is the unique maximal complexity measure satisfying a natural
      set of axioms. This reveals a strong relationship between hierarchical complexity
      in biological systems and the area of algebra known as global semigroup theory.
      We then study the rate at which hierarchical complexity can evolve in biological
      systems assuming evolution is "as slow as possible" from the perspective of
      computational power of organisms. Explicit bounds on the evolution of complexity
      are derived showing that, although the evolutionary changes in hierarchical
      complexity are bounded, in some circumstances complexity may more than double in
      certain "genius jumps" of evolution. In fact, examples show that our bounds are
      sharp. We sketch the structure where such complexity jumps are known to occur and
      note some similarities to previously identified mechanisms in biological
      evolutionary transitions. We also address the question of, How fast can
      complexity evolve over longer periods of time? Although complexity may more than
      double in a single generation, we prove that in a smooth sequence of t
      "inclusion" steps, complexity may grow at most from N to (N + 1)t + N, a linear
      function of number of generations t, while for sequences of "mapping" steps it
      increases by at most t. Thus, despite the fact that there are major transitions
      in which complexity jumps are possible, over longer periods of time, the growth
      of complexity may be broken into maximal intervals on which it is bounded above
      in the manner described.

PMID- 10943666
TI  - Duplication of modules facilitates the evolution of functional specialization.
AB  - The evolution of simulated robots with three different architectures is studied
      in this article. We compare a nonmodular feed-forward network, a hardwired
      modular, and a duplication-based modular motor control network. We conclude that
      both modular architectures outperform the non-modular architecture, both in terms
      of rate of adaptation as well as the level of adaptation achieved. The main
      difference between the hardwired and duplication-based modular architectures is
      that in the latter the modules reached a much higher degree of functional
      specialization of their motor control units with regard to high-level behavioral
      functions. The hardwired architectures reach the same level of performance, but
      have a more distributed assignment of functional tasks to the motor control
      units. We conclude that the mechanism through which functional specialization is
      achieved is similar to the mechanism proposed for the evolution of duplicated
      genes. It is found that the duplication of multifunctional modules first leads to
      a change in the regulation of the module, leading to a differentiation of the
      functional context in which the module is used. Then the module adapts to the new
      functional context. After this second step the system is locked into a
      functionally specialized state. We suggest that functional specialization may be
      an evolutionary absorption state.

PMID- 10943667
TI  - Shapes in the shadow: evolutionary dynamics of morphogenesis.
AB  - This article investigates the evolutionary dynamics of morphogenesis. In this
      study, morphogenesis arises as a side-effect of maximization of number of cell
      types. Thus, it investigates the evolutionary dynamics of side-effects.
      Morphogenesis is governed by the interplay between differential cell adhesion,
      gene-regulation, and intercellular signaling. Thus, it investigates the potential
      to generate complex behavior by entanglement of relatively "boring" processes,
      and the (automatic) coordination between these processes. The evolutionary
      dynamics shows all the hallmarks of evolutionary dynamics governed by nonlinear
      genotype phenotype mapping: for example, punctuated equilibria and diffusion on
      neutral paths. More striking is the result that interesting, complex
      morphogenesis occurs mainly in the "shadow" of neutral paths which preserve cell
      differentiation, that is, the interesting morphologies arise as mutants of the
      fittest individuals. Characteristics of the evolution of such side-effects in the
      shadow appear to be the following: (1) The specific complex morphologies are
      unique (or at least very rare) among the set of de novo initiated evolutionary
      histories. (2) Similar morphologies are reinvented at large temporal distances
      during one evolutionary history and also when evolution is restarted after the
      main cell differentiation pattern has been established. (3) A mosaic-like
      evolution at the morphological level, where different morphological features
      occur in many combinations, while at the genotypic level recombination is not
      implemented and genotypes diverge linearly and at a constant rate.

PMID- 10943668
TI  - The intrastromal corneal ring in clinical refractive surgery: reference to
      results in rabbit eyes.
AB  - BACKGROUND: The intrastromal corneal ring (ISR) is a refractive device recently
      introduced for clinical application that is implanted in the mid-peripheral
      corneal stroma in order to correct myopia without invasion of the central optical
      zone. First clinical results of intracorneal ring segment implantation were
      published recently. These results reveal striking similarities to our own
      experimental data, only briefly published up to now. The aim of this study is to
      present the refractive and histopathological data of ISR implants in rabbits and
      to compare these results with the clinical data actually available. METHODS:
      Expansion/constriction effects were evaluated with a ring of constant size (7.5 x
      0.5 x 0.2 mm) in channels of 7.0, 7.5, or 8.0 mm in diameter, volume effects by
      implantation of 7.5-mm rings with varying thickness (0.2, 0.3, 0.4 mm) into a
      channel of 7.5 mm, respectively. Refractive power was measured preoperatively and
      at day (D) 7, D14, D30 for the first and the second experiment, plus D60, D90 for
      the second experiment. Histological evaluations of the induced morphological
      changes were additionally performed at all time intervals. RESULTS: Significant
      (P<0.05) flattening of the cornea was obtained in all but the first (constant
      ring, 7.0-mm channel) implants postoperatively at D7 and/or D14, with mean
      dioptric changes up to -5.03+/-2.92 compared with controls. However, from D30 on,
      there was no statistically significant difference between operated and control
      eyes. Biomicroscopy and histology of the implanted eyes revealed good
      biocompatibility, with only rare major complications such as stromal abscess or
      massive neovascularization. CONCLUSIONS: Although our implantation technique
      differs slightly from that employed in the recent FDA studies, our results tend
      to confirm the maximal achievable refractive change of about -5 dpt with this
      procedure. Furthermore, this study is the first to demonstrate that in rabbits,
      ISR implantation has only a shortterm effect on refractive power. Our results
      indicate that long-term refractive follow-up may be necessary in human eyes prior
      to the introduction of ISRs as a routine procedure in refractive surgery.

PMID- 10943669
TI  - Bilateral optic neuropathy after bone marrow transplantation and cyclosporin A
      therapy.
AB  - BACKGROUND: Cyclosporin A (CsA) is widely used as a prophylactic and therapeutic
      agent against graft-versus-host disease after bone marrow transplantation. Under
      this condition optic neuropathy has been found and considered as a possible side
      effect of cyclosporin A. CASE REPORT: A 52-year-old man presented with bilateral
      optic disc swelling and visual loss 6 months after bone marrow transplantation.
      Cyclosporin A was the only medication with a known neurotoxic side effect. After
      cessation of cyclosporin A and treatment with oral prednisone, vision improved
      within 2 months. Optic disc swelling ameliorated within 6 months but partial
      optic atrophy developed. DISCUSSION: Cyclosporin A given after bone marrow
      transplantation may have caused bilateral optic neuropathy in our patient.
      Microangiopathy of the optic nerve may be the pathogenetic mechanism.

PMID- 10943670
TI  - Search for an optimal combination of structural and functional parameters for the
      diagnosis of glaucoma. Multivariate analysis of confocal scanning laser
      tomograph, blue-on-yellow visual field and retinal nerve fiber layer data.
AB  - BACKGROUND: The purpose of this study was to evaluate which of the structural and
      functional parameters--the Heidelberg Retina Tomograph (HRT), white-on-white
      (W/W) and blue-on-yellow (B/Y) visual fields and semiquantitative retinal nerve
      fiber layer (RNFL) scoring parameters--can give the best separation between non
      glaucomatous and glaucomatous eyes. METHODS: Fifty-five subjects were included in
      this study: 32 nonglaucomatous subjects with mean age of 54 years, and 23
      patients with ocular hypertension or glaucoma and mean age of 59 years. The HRT
      with software 1.11, the Humphrey 30-2 W/W and lens coloration-corrected B/Y
      visual fields, and semiquantitative RNFL scores were utilized. Stepwise logistic
      regression analysis was used in finding, from a given set of parameters, a best
      discriminating parsimonious subset to a logistic model, the discriminatory
      performance of which was evaluated by the area under the ROC curve. RESULTS: When
      all the structural and functional variables were considered, the RNFL total
      overall score gave the best separation between glaucomatous and non-glaucomatous
      eyes (ROC area 0.98). Without the RNFL scores and optic disc size-dependent HRT
      parameters in the model, the cup shape measure was selected first (ROC area
      0.88). In the second step the RNFL thickness was selected (ROC area 0.91), and in
      the third step the corrected B/Y mean deviation (MD) was selected (ROC area
      0.91). With only the HRT parameters in the model, the cup/disc ratio was selected
      first (ROC area 0.88). However, when the groups were matched for optic disc size,
      all disc size-dependent HRT variables lost their discriminant power. CONCLUSION:
      Cup shape measure and RNFL thickness, together with age- and lens coloration
      corrected MD of the B/Y perimetry provided good discrimination between healthy
      individuals and patients with glaucoma.

PMID- 10943671
TI  - Relationship between anticoagulant medication and massive intraocular hemorrhage
      in age-related macular degeneration.
AB  - BACKGROUND: A massive intraocular hemorrhage in the course of age-related macular
      degeneration (AMD) is a devastating event. We set out to determine the role of
      anticoagulant therapy prescribed for vascular or cardiac indications in the
      development of a massive hemorrhage. METHODS: A retrospective case-controlled
      study was conducted of 50 cases of age-related macular degeneration complicated
      by massive subretinal and vitreous hemorrhage. The control group consisted of 50
      cases of AMD with small subretinal hemorrhage. RESULTS: There was a significant
      difference in the use of anticoagulant medication (warfarin sodium) between the
      groups. The difference in the use of antiplatelet medication (aspirin) between
      the groups was not significant. A patient with a massive intraocular hemorrhage
      and AMD is 11.6 times more likely to use anticoagulant medication. It appeared
      that more than 50% of the patients in the massive hemorrhage group were allowed
      to stop the anticoagulant medication. CONCLUSION: Anticoagulant medication poses
      a significant risk in the development of a massive intraocular hemorrhage in
      patients with exudative AMD. Antiplatelet medication poses a less significant
      risk. Physicians prescribing anticoagulant medication should be informed about
      the macular status of the patient. the In case of neovascular AMD, anticoagulant
      medication should be prescribed only for absolute systemic indications.

PMID- 10943672
TI  - N-methyl-D-aspartate receptor subunit mRNA expression in human retinal ganglion
      cells.
AB  - PURPOSE: To determine the expression of mRNA coding for different N-methyl-D
      aspartate receptor (NR) subunits in the human retina. METHODS: In five human eyes
      the distribution of NR subunit mRNA was determined by in situ hybridization using
      35S-labeled cRNA probes. In 100 consecutive retinal ganglion cells of each eye
      the level of mRNA expression of the different NR subunits was qualitatively
      graded. RESULTS: Ninety-three percent of retinal ganglion cells expressed mRNA
      coding for NR1, 9% for NR2A, 28% for NR2B, 86% for NR2C, and 84% for NR2D. The
      pattern of expression did not vary among the five eyes. CONCLUSION: These data
      establish distinct expression profiles of NR subunits in human retinal ganglion
      cells and suggest the development of specific NR ligands to reduce excitotoxic
      retinal ganglion cell loss.

PMID- 10943673
TI  - Increased growth factor activity in the aqueous humour of patients with
      exfoliation syndrome.
AB  - BACKGROUND: To investigate the growth factor activity in the aqueous humour of
      patients with exfoliation syndrome (XFS). METHODS: We collected 154 aqueous
      humour samples (69 from patients with XFS and 85 from age-matched controls) prior
      to routine extracapsular cataract surgery. Growth factor activity was
      investigated using a [3H]thymidine incorporation assay on McCoy cells that
      assesses DNA synthesis. Albumin concentration was measured by a radio-immunoassay
      as an index of blood aqueous barrier integrity. N-Acetylglucosaminidase (NAG)
      activity, a marker of cellular breakdown, was ascertained by a fluorometric
      method. RESULTS: XFS aqueous samples exhibited significantly higher growth factor
      activity than to the control samples (P<0.001). Albumin concentration was also
      higher in the XFS group. NAG activity was similar in the two groups. No
      relationship between growth factor activity and the other parameters investigated
      was found. CONCLUSIONS: Increased growth factor activity was detected in the
      aqueous humour of patients with XFS. This finding may be related to the
      pathogenesis of XFS.

PMID- 10943674
TI  - What happens to tears inside the efferent lacrimal passage? An animal
      experimental study.
AB  - BACKGROUND: To determine whether absorption of protein components of the tear
      fluid occurs in normal efferent tear ducts, an animal experiment was carried out.
      METHODS: Iodinated albumin was dropped into eyes of female rats. After 10, 20 or
      60 min the rats were killed, blood collected and the heads embedded for
      histological examination. Serum was obtained from the clotted blood and the
      radioactivity in a protein sediment and the combined supernatants counted. In a
      second approach, serum was fractionated by molecular mass and radioactivity in
      the fractions measured. Furthermore, autoradiographs of rat head sections were
      performed. RESULTS: Uptake of radioactivity into the serum was low, but increased
      with time. After 60 min maximal incorporation of the applied radioactivity into
      the blood was 0.13%; most (70-80%) of the incorporated radioactivity was not
      protein bound. Gel chromatographic separation according to molecular mass yielded
      fractionated peaks of radioactivity corresponding to albumin with maximal 4.8
      Bq/ml serum, iodinated tyrosine (5.5 Bq/ml), and free iodine (237 Bq/ml; each
      after 60 min). Histologically the rat efferent lacrimal tear ducts showed a
      multilayered lining epithelium with integrated goblet cells in a characteristic
      arrangement of several cells. In autoradiographs of rat head sections no
      transport of radioactivity could be visualized. CONCLUSION: In rats only traces
      of iodinated albumin are incorporated from the efferent lacrimal tear ducts into
      the blood. A higher proportion of the radioactivity is taken up as the
      proteolytic degradation product of bovine serum albumin to free amino acids, and
      96% of the radioactivity incorporated was free iodine, probably as a contaminant
      of the iodinated preparation.

PMID- 10943675
TI  - Glutamine synthetase and marker enzymes of the blood-retina barrier in fetal
      bovine retinal pigment epithelial cells.
AB  - BACKGROUND: Glutamine synthetase is involved in the recycling of synaptically
      released glutamate and GABA and in the detoxification of ammonia. It is present
      in the Muller cells of the neural retina but not in the retinal pigment
      epithelial (RPE) cells of adult mammals. In human retinal pathological conditions
      glutamine synthetase has also been detected in RPE cells. In this case glutamine
      synthetase may provide the cells with glutamine needed for proliferation.
      Proliferation is also intense during retinal development. METHODS: We studied the
      distribution of glutamine synthetase immunoreactivity in fetal bovine retinae,
      especially in the RPE. The maturity of the RPE was demonstrated by histochemical
      detection of gamma-glutamyltranspeptidase, alkaline phosphatase and Na/K-ATPase
      as marker enzymes for the blood-retina barrier and by electron microscopy.
      RESULTS: We found that in the first 3 months of gestation glutamine synthetase
      immunoreactivity is located exclusively in the RPE. During the 3rd month the
      marker enzymes of the blood-retina barrier begin to appear. From the 4th month
      on, RPE cells are glutamine synthetase immunonegative. CONCLUSION: Glutamine in
      RPE cells in early development may supply glutamine for the intensely
      proliferating cells in the retina. Glutamine synthetase immunoreactivity in human
      retinal pathological conditions may indicate reinduction of an enzyme used in
      earlier development.

PMID- 10943676
TI  - Apoptosis is present in the primate macula at all ages.
AB  - BACKGROUND: It has become increasingly clear that apoptosis is a main event in
      photoreceptor cell death in a variety of retinal degenerations. We investigated
      the role of apoptosis in the physiologically aging primate macula. METHODS:
      Twenty maculae of rhesus monkeys, aged 6-34 years, were investigated. Apoptosis
      was determined in formalin-fixed, paraffin-embedded eyes using the TUNEL (TdT
      mediated dUTP-biotin nick end labeling) method and quantitatively analyzed.
      Morphology of TUNEL-positive cells was studied by confocal laser microscopy and
      transmission electron microscopy. The thickness of the outer nuclear layer (ONL)
      was determined by image analysis. Furthermore, expression of apoptosis-regulating
      proteins Bcl-x, Fas and Fas Ligand was studied by immunohistochemistry. RESULTS:
      TUNEL-positive nuclei showed apoptotic features on confocal laser microscopy.
      They were scattered and sparsely found in the macula, most frequently in the ONL.
      The thickness of the ONL decreased with increasing age. Apoptosis was found
      equally distributed at all ages, although in the two oldest maculae up to 13
      times more apoptosis was found. Expression of Bcl-x, Fas and Fas Ligand was equal
      at all ages. CONCLUSION: Our findings indicate that apoptosis in the primate
      macula occurs at all ages at similar rates, possibly increasing in the oldest age
      group, and may account for the decreasing thickness of the primate macula with
      age.

PMID- 10943677
TI  - Epinephrine, but not dexamethasone, induces apoptosis in retinal pigment
      epithelium cells in vitro: possible implications on the pathogenesis of central
      serous chorioretinopathy.
AB  - BACKGROUND: The pathogenesis of central serous chorioretinopathy is poorly
      understood. It is believed to be due to dysfunction of the retinal pigment
      epithelium and/or choroid and has been associated with elevated levels of
      epinephrine and administration of corticosteroids. Epinephrine and
      corticosteroids have previously been shown to induce apoptosis (programmed cell
      death) in various types of cells. The objective of this study was to investigate
      whether these agents can induce apoptosis in cultured retinal pigment epithelium
      cells. This may help elucidate the pathogenesis of central serous
      chorioretinopathy. METHODS: Third-passage porcine retinal pigment epithelium
      cells were grown to confluence and incubated for 1-7 days in culture medium
      containing epinephrine (10(2)-10(9) pg/ml) or a corticosteroid, dexamethasone (4
      4x10(4) ng/ml). The cultures were evaluated for apoptosis by phase-contrast
      microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling. RESULTS: Epinephrine (7x10(7)-10(9) pg/ml) induced apoptosis in a
      dose- and time-dependent manner. Exposure to lower concentrations of epinephrine
      (10(2)-6x10(7) pg/ml) and all tested levels of dexamethasone did not result in
      apoptosis. CONCLUSION: Retinal pigment epithelium cells may undergo apoptosis
      following exposure to elevated levels of epinephrine. These findings suggest a
      possible pathophysiologic mechanism for the development of central serous
      chorioretinopathy.

PMID- 10943678
TI  - Synthesis of hyaluronan by normal and wounded rabbit iris.
AB  - BACKGROUND: Endogenous hyaluronan has been found in different tissues in the
      normal and traumatized eye. However, the main source, the biological aspects and
      the full potential role of hyloronan are still unclear. METHODS: Hyaluronan
      production was studied both in organ culture and in vivo, using a double-label
      protocol with [35S]sulfate and [3H]glucosamine. RESULTS: [3H]glucosamine and
      [35S]sulfate were incorporated into hyaluronan and sulfated glycosaminoglycans in
      normal and in traumatized iris tissue in organ culture and in vivo. There was low
      relative hyaluronan synthesis in vivo, only 2% of total incorporated
      [3H]glucosamine in normal irides. Increased relative incorporation of
      [3H]glucosamine into hyaluronan was seen after operative trauma to iris tissue
      both in vivo and in vitro. CONCLUSION: Our findings demonstrate synthesis of
      hyaluronan by normal and traumatized iris. The iris seems to be the most
      important source of aqueous hyaluronan.

PMID- 10943679
TI  - The effect of corticosteroid and cyclosporin A on murine corneal allograft
      rejection.
AB  - BACKGROUND: The immunomodulatory T-helper type 1 (Th1) cytokine interferon-gamma
      (IFN-gamma) was measured in serum and cornea to ascertain its general
      contribution to corneal graft rejection and to establish a rational basis for the
      decision for or against systemic therapy. METHODS: Eight groups of differently
      treated BALB/c (H-2d) mice received a C3H (H-2 k) corneal graft. There was one
      saline-treated control group and two groups that received intramuscular
      cyclosporin A (CsA) for 14 or 40. Three groups received systemic or topical,
      systemic plus topical corticosteroid treatment, which was combined with CsA in
      two further groups. To measure the IFN-gamma level by enzyme-linked immunosorbent
      assay (ELISA), blood was taken by heart puncture and corneae were excised at the
      limbus. RESULTS: Five days of systemic corticosteroid and 14 days of CsA had no
      significant effect on graft survival. A 40-day CsA treatment and a 40-day
      combined corticosteroid treatment significantly prolonged graft survival. An 80
      day topical corticosteroid treatment produced additional prolongation. IFN-gamma
      could not be detected (limit of detection 25 pg/ml) in any of the serum samples,
      while significantly increased amounts of IFN-gamma were detected in the
      supernatants of the corneal tissue 13 or 14 days after allogeneic but not
      syngeneic corneal graft, corresponding to 9.5 pg, 5.1 pg and 1.8 pg per cornea.
      CONCLUSION: The detection of Th1 cytokines in the cornea but not the serum of
      mice at the time of allograft rejection is in accordance with the finding of long
      lasting dose-dependent immunosuppression of topical steroids and the inefficacy
      of short-term systemic CsA and corticosteroids.

PMID- 10943680
TI  - Survival of corneal allografts following adenovirus-mediated gene transfer of
      interleukin-4.
AB  - BACKGROUND: Genetic manipulation of the donor cornea ex vivo prior to
      transplantation may allow modulation of the allogeneic immune response following
      penetrating keratopasty. In this study we investigated the effect of adenovirus
      mediated gene transfer of the Th2 cytokine interleukin-4 (IL-4) to rat corneas in
      an experimental keratoplasty model. METHODS: Ex vivo manipulation of Wistar-Furth
      rat corneas was performed using E1/E3-deleted adenoviral vectors transferring the
      gene for rat IL-4 (AdrIL-4) under control of the CMV promoter. Following
      transfection with AdrIL-4 (2 x 10(8) pfu) in DMEM/2% FCS for 3 h, donor corneas
      were transplanted in MHC class I/II-incompatible Lewis rats. Fifty-two Lewis rats
      were randomly assigned to receive either nontransfected grafts (n=32), AdrIL-4
      transfected grafts (n=8), or syngeneic grafts (n=12). RESULTS: The rejection rate
      of AdrIL-4-transfected grafts (85.7%) could not be reduced as compared to
      controls (62.9%). In addition, the mean survival time of AdrIL-4-transfected
      grafts (12.6+/-4.5 days) did not differ (P>0.05) from that for untreated
      transplants (14.1+/-3.8 days). CONCLUSIONS: Our results indicate that
      overexpression of IL-4 is not sufficient to reduce the rejection rate of corneal
      allografts in an experimental keratoplasty model. Further investigations are
      necessary to identify the reasons for failure and establish more efficient
      modulatory approaches.

PMID- 10943681
TI  - R-(+)-verapamil, S-(-)-verapamil, and racemic verapamil inhibit human retinal
      pigment epithelial cell contraction.
AB  - PURPOSE: To evaluate the effects of R-(+)-verapamil, S-(-)-verapamil, and the
      racemate on in vitro contraction of human retinal pigment epithelial cells.
      METHODS: RPE cells from human donor eyes were enzymatically dissociated and
      cultured on collagen gels. Transdifferentiated RPE cells (seventh and eighth
      passage) were used for experiments. The contraction assays were treated with
      different concentrations (10-1000 microM) of R-(+)-verapamil, S-(-)-verapamil,
      and racemic verapamil. RESULTS: Verapamil inhibited the gel contraction of human
      RPE cells. R-(+)-verapamil, S-(-)-verapamil, and racemic verapamil acted equally
      in a dose-dependent manner from 10-1000 microM. CONCLUSION: The results indicate
      the effectiveness of verapamil to inhibit the contraction of RPE cells. R-(+)
      verapamil is recommended because it is associated with fewer systemic and local
      side effects.

PMID- 10943682
TI  - Why can't you tickle yourself?
AB  - It is well known that you cannot tickle yourself. Here, we discuss the proposal
      that such attenuation of self-produced tactile stimulation is due to the sensory
      predictions made by an internal forward model of the motor system. A forward
      model predicts the sensory consequences of a movement based on the motor command.
      When a movement is self-produced, its sensory consequences can be accurately
      predicted, and this prediction can be used to attenuate the sensory effects of
      the movement. Studies are reviewed that demonstrate that as the discrepancy
      between predicted and actual sensory feedback increases during self-produced
      tactile stimulation there is a concomitant decrease in the level of sensory
      attenuation and an increase in tickliness. Functional neuroimaging studies have
      demonstrated that this sensory attenuation might be mediated by somatosensory
      cortex and anterior cingulate cortex: these areas are activated less by a self
      produced tactile stimulus than by the same stimulus when it is externally
      produced. Furthermore, evidence suggests that the cerebellum might be involved in
      generating the prediction of the sensory consequences of movement. Finally,
      recent evidence suggests that this predictive mechanism is abnormal in patients
      with auditory hallucinations and/or passivity experiences.

PMID- 10943683
TI  - Suppression of vision by transcranial magnetic stimulation: a third mechanism.
AB  - We recently reported three periods when single-pulse transcranial magnetic
      stimulation (TMS) of the occipital pole impaired performance on a forced-choice
      visual letter-identification task. TMS-induced suppression during these periods
      is best explained by a blink-associated covering of the pupils and by a direct
      interference with letter-processing neural activity. We now report TMS-induced
      suppression at times that seem too late for the suppression to be explained by
      the first mechanism and too early for the suppression to be explained by the
      second mechanism. The most likely explanation is a blink-associated interference
      with letter-processing neural activity.

PMID- 10943684
TI  - Differential response in the human amygdala to racial outgroup vs ingroup face
      stimuli.
AB  - Here we describe response in the human amygdala to the presentation of racial
      outgroup vs ingroup faces. Functional magnetic resonance imaging (fMRI) measures
      of brain activity were acquired while subjects who identified themselves as White
      or Black viewed photographs of both White and Black faces. Across all subjects,
      we observed significantly greater blood oxygen-level-dependent (BOLD) signal in
      the amygdala to outgroup vs ingroup faces, but only during later stimulus
      presentations. A region of interest (ROI)-based analysis of these voxels revealed
      a significant interaction between amygdala response to outgroup and ingroup faces
      over time. Specifically, the greater amygdala activation to outgroup faces during
      later stimulus presentations was the result of amygdala response habituation to
      repeated presentations of ingroup faces with sustained responses to outgroup
      faces. The present results suggest that amygdala responses to human face stimuli
      are affected by the relationship between the perceived race of the stimulus face
      and that of the subject. Results are discussed as consistent with a role for the
      amygdala in encoding socially and/or biologically relevant information. We
      conclude that researchers seeking to study brain responses to face stimuli in
      human subjects should consider the relationship between the race of subjects and
      stimuli as a significant potential source of variance. Moreover, these data
      provide a foundation for future related studies in the neuroscience of social
      cognition and race.

PMID- 10943685
TI  - Theta synchronization predicts efficient memory encoding of concrete and abstract
      nouns.
AB  - Functional and topographical differences between processing of spoken nouns which
      were remembered or which were forgotten were shown by means of EEG coherence
      analysis. Later recalled nouns were related with increased neuronal
      synchronization (= cooperation) between anterior and posterior brain regions
      regardless of presented word category (either concrete or abstract nouns).
      However, theta coherence exhibited topographical differences during encoding of
      concrete and abstract nouns whereby former were related with higher short-range
      (mainly intrahemispheric), later with higher long-range (mainly interhemispheric)
      coherence. Thus, theta synchronization possibly is a general phenomenon always
      occurring if task demand increases and more efficient information processing is
      required. Measurement of EEG coherence yields new information about the neuronal
      interaction of involved brain regions during memory encoding of different word
      classes.

PMID- 10943686
TI  - Early postnatal development of functional ocular dominance columns in cat primary
      visual cortex.
AB  - During postnatal development of the visual cortex the thalamocortical afferents
      serving the two eyes segregate into alternating patches called ocular dominance
      (OD) columns. Interested in the dynamics of this segregation process we studied
      the appearance of functional OD columns in the primary visual cortex of normally
      raised and strabismic kittens aged 2-6 weeks using 2-deoxyglucose labelling in
      awake animals. In both experimental groups, OD columns covering the entire area
      17 and spanning all cortical laminae are first visible at 3 weeks and appear
      already adult-like at 4 weeks, much earlier than thought on the basis of previous
      anatomical studies. We hypothesize that a small and anatomically undetectable
      imbalance between the afferents from the two eyes is amplified by intracortical
      interactions so that their activity patterns become different and may guide the
      segregation process of the afferents in cortical layer IV.

PMID- 10943687
TI  - The nociceptin/orphanin FQ receptor antagonist, [Nphe1]NC(1-13)NH2, potentiates
      morphine analgesia.
AB  - Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel
      peptide/receptor system which has been implicated in the regulation of various
      central functions, including pain. The aim of the present study was to explore
      the involvement of the endogenous NC/OP4 system in the modulation of opioid
      analgesia using the selective OP4 receptor antagonist [Nphe1]NC(1-13)NH2.
      Experiments were performed in mice exposed to acute as well as chronic treatment
      with morphine. [Nphe1]NC(1-13)NH2, injected i.c.v. at 30 nmol, strongly
      potentiated the analgesic effect of supraspinal morphine (1 nmol, i.c.v.) while
      it only slightly increased the antinociceptive activity of morphine given
      systemically (5 mg/kg, s.c.). [Nphe1]NC(1-13)NH, (30 nmol, i.c.v.) also
      potentiated morphine analgesia in mice made tolerant to the opiate (30 mg/kg/day
      for 4 days). These findings implicate the endogenous NC signaling as a modulator
      of morphine analgesia and tolerance.

PMID- 10943689
TI  - Automatic object identification: an fMRI study.
AB  - Boucart and Humphreys reported an automatic access to object identity when
      observers attend to a physical property of the form of an object (e.g. the
      orientation) but not to its colour. We sought evidence for automatic
      identification in a brain imaging study using fMRI. In an orientation decision
      task participants decided whether a picture was vertical or horizontal. In the
      colour decision task participants decided if a picture was blue or green.
      Activation of areas 18-19 was found for both color and orientation. Activation of
      the temporal area 37 occurred more frequently in the orientation than in the
      colour decision task. This result suggests that automatic identification
      activates the same brain area as overt processing of semantic information.

PMID- 10943688
TI  - Corticotropin-releasing factor receptor type I mediates stress-induced relapse to
      opiate dependence in rats.
AB  - The possible effect of different corticotropin-releasing factor receptor (CRFR)
      antagonists (alpha-helical CRF, CP-154,526 and AS-30) on the maintenance and
      reactivation of morphine-conditioned place preference (CPP) induced by morphine
      or footshock stress, respectively, were investigated in rats. The results show
      that morphine-induced maintenance of CPP was not affected by pretreatment with
      any CRFR antagonists. However, morphine-induced the reactivation of CPP was
      significantly attenuated by pre-administration of 10 microg alpha-helical CRF
      (i.c.v.). The maintenance of morphine CPP could be induced by repeated footshock
      and this effect was significantly attenuated by pretreatment of 10 microg alpha
      helical CRF (i.c.v.) and 10 mg CP-154,526 (i.p.). Furthermore, following a 28-day
      extinction of morphine CPP, a single footshock could again elicit the
      reactivation of place preference that was blocked by pretreatment with 10 microg
      alpha-helical CRF (i.c.v.) and 1 or 10 mg CP-154,526 (i.p.). The present study
      demonstrates that CRFR type 1, but not CRFR type 2, mediates the stress-induced
      maintenance and reactivation of morphine CPP. These findings suggest that CRFR
      type 1 antagonists might be of some value in the treatment and prevention of
      stress-induced relapse to drug dependence long after detoxification.

PMID- 10943690
TI  - Differential expression of c-fos following administration of two tremorgenic
      agents: harmaline and oxotremorine.
AB  - The regional distribution of c-Fos expression in the brain after the
      administration of two tremorgenic agents was studied. In both the harmaline- and
      oxotremorin-treated rats, c-Fos-positive neurons were extensively distributed in
      the basal ganglia nuclei and the cerebellum. Additionally, in the harmaline
      treated rats, numerous c-Fos-positive neurons were also distributed throughout
      the inferior olivary nucleus. In the oxotremorine-treated rats, while the
      inferior olive was not involved, c-Fos was strongly expressed in the neurons of
      the reticular thalamic nucleus, possibly due to the muscarinic effects of
      oxotremorine. The present study revealed that the inferior olive is selectively
      activated in the harmaline-administered animals and that the basal ganglia are
      involved in both harmaline- and oxotremorine-induced tremors.

PMID- 10943691
TI  - Brain choline acetyltransferase reduction in SIV infection. An index of early
      dementia?
AB  - HIV infection at late stages is associated with neurological complications
      including impaired motor and cognitive functions. We used simian immunodeficiency
      (SIV)-infected rhesus monkeys, an animal model of HIV infection, to investigate
      changes in choline acetyltransferase (ChAT) activity, a biochemical marker of
      cognitive function, in post-mortem brains during early, asymptomatic SIV
      infection and AIDS. ChAT activity was dramatically reduced in putamen and
      hippocampus already during asymptomatic infection. In animals with AIDS, ChAT
      activity was further decreased. The reduction of ChAT was not related to brain
      viral load or CNS pathological lesions. Our results demonstrate deficits in ChAT
      activity already during the first months of SIV infection and imply that
      cognitive dysfunction may occur early in immunodeficiency viral infections.

PMID- 10943693
TI  - Time course of conscious and unconscious semantic brain activation.
AB  - Event-related brain potentials (ERPs) were used to investigate the
      neurophysiological correlates of conscious and unconscious semantic processing.
      Masked words, which do not enter consciousness, as well as visible words, were
      shown to modulate the N400 ERP potential to subsequently presented, meaningfully
      related target words. The N400 is known as an electrophysiological index of
      semantic processing. However, for unconsciously perceived words semantic brain
      activation decays fast within 200 ms, but increases with time for consciously
      perceived words. Thus, conscious and unconscious semantic activation involves
      similar brain areas, but both forms of processes exhibit distinct, qualitatively
      different time courses.

PMID- 10943692
TI  - Cocaine effects on gene regulation in the striatum and behavior: increased
      sensitivity in D3 dopamine receptor-deficient mice.
AB  - Central effects of psychostimulants such as cocaine are predominantly mediated by
      dopamine receptors. We have used mice with a targeted deletion of the D3 dopamine
      receptor subtype to investigate the role of this receptor in the regulation of
      gene expression in striatal neurons and behavior by acute and repeated treatment
      with cocaine (25 mg/kg). In mice lacking D3 receptors, acute administration of
      cocaine has more pronounced stimulatory effects on c-fos and dynorphin expression
      in the dorsal and ventral striatum. The behavioral response to cocaine is also
      increased in these mice. These findings indicate that the D3 receptor plays an
      inhibitory role in the action of cocaine on behavior and gene regulation in the
      striatum.

PMID- 10943694
TI  - An fMRI study of the lateralization of motor cortex activation in acallosal
      patients.
AB  - Transcranial magnetic stimulation (TMS) studies have suggested that callosal
      afferents may mediate inhibition of the ipsilateral motor cortex (IMC) during
      unilateral hand movements. To test this concept, we used fMRI to determine
      whether acallosal patients have increased IMC activation with either complex or
      simple unilateral finger movements. Neither the localization of motor cortical
      regions activated, the volumes of activation, or the relative hemispheric
      lateralization of activations were different between the patients and normal
      controls. The potential callosal inhibitory pathway identified by TMS therefore
      does not appear to contribute to the interhemispheric suppression of
      physiologically relevant activations in the motor cortex as measured by fMRI.

PMID- 10943695
TI  - Human brain sub-systems for discrimination of visual shapes.
AB  - To investigate whether stereo and plane visual shapes are processed in the same
      brain system, participants were instructed to discriminate whether two visual
      stimuli presented in sequence were identical and event-related potential (ERP)
      was recorded from their scalp. The first (S1) and the second stimuli (S2) were
      the same stereo shapes in condition 1, but were different in condition 3. They
      were the same plane shapes in condition 2, but different in condition 4. A
      negative component (N270) was recorded in condition 3 and 4, which showed the
      maximal amplitude in the right posterior scalp in condition 3 and in the anterior
      scalp in condition 4. A different cognition mechanism is involved in the
      processing of non-matched stereo and plane visual shapes.

PMID- 10943696
TI  - Different distribution of nifedipine- and omega-conotoxin GVIA-sensitive Ca2+
      channels in rat hippocampal neurons.
AB  - The distribution patterns of nifedipine- and omega-conotoxin GVIA-sensitive Ca2+
      channels in rat primary cultured hippocampal neurons were investigated with a
      confocal laser-scanning microscope. Cells were loaded with the calcium indicator
      dye Oregon Green/AM, and the responses to high potassium (90 mM) solution with
      and without the existence of L- and N-type Ca2+ channel blockers were imaged. In
      general, extracellular application of high [K+] solution induced a [Ca2+]o
      dependent increase of [Ca2+]i in both somata and dendritic processes. The
      increase was reduced by a N-type channel blocker, omega-conotoxin GVIA, and the
      reduction was greater in dendritic processes than in somata and proximal
      dendrites. In contrast, the reduction induced by the L-type calcium channel
      blocker, nifedipine, was observed evenly all over the neurons. The results
      demonstrated the heterogeneous distribution of nifedipine- and omega-conotoxin
      GVIA-sensitive calcium channels in cultured hippocampal neurons.

PMID- 10943697
TI  - Thermogenesis mediated by a capsaicin-sensitive area in the ventrolateral
      medulla.
AB  - Systemic administration of capsaicin elicits heat production, which can be
      observed in decerebrated preparations but is blocked by spinal transection. To
      identify the critical locus involved in the capsaicin-induced thermogenesis in
      the brainstem, we studied the effect of capsaicin on rats with bilateral
      electrolytic lesions in the premotor areas of sympathoadrenal preganglionic
      neurons. Lesions in the rostral ventrolateral medulla (RVLM), but not in other
      regions, largely attenuated the capsaicin-induced heat production. Unilateral
      microinjection of 30-100 nl capsaicin (0.5%, w/v) into the RVLM elicited a heat
      production response, whereas capsaicin injection in neighboring areas or vehicle
      injection into the RVLM did not affect heat production. These results suggest
      that the thermogenic effect of capsaicin is mediated, at least in part, by some
      capsaicin-sensitive structure in the RVLM.

PMID- 10943698
TI  - The effects of intra-vestibular nucleus administration of brain-derived
      neurotrophic factor (BDNF) on recovery from peripheral vestibular damage in
      guinea pig.
AB  - Brain-derived neurotrophic factor (BDNF), at doses of 0.04, 0.4 or 4.0
      microg/day, was delivered by cannula and s.c osmotic minipump into the
      ipsilateral vestibular nucleus complex from 0 to 50 h following unilateral
      labyrinthectomy (UL) in guinea pigs. Compared to the vehicle control group, the
      frequency of spontaneous nystagmus was significantly reduced (p < 0.02) and the
      rate of yaw head tilt compensation increased (p < 0.02). However, roll head tilt
      was not signifcantly affected. There were also no significant effects of BDNF
      administration into the IVth ventricle (4.0 microg/day) on any UL symptom. These
      results further support the hypothesis that neurotrophins such as BDNF may
      enhance the vestibular compensation process.

PMID- 10943699
TI  - Viral infection of developing GABAergic neurons in a model of hippocampal
      disinhibition.
AB  - Mechanisms by which perinatal viral infections can disrupt hippocampal
      development and cause selective neuronal death may have implications for temporal
      lobe epilepsy and schizophrenia. Despite abnormalities of inhibitory interneurons
      in these diseases, the causal relationships between such neurotransmitter changes
      and viral infections remain unclear. This relationship was examined in a model in
      which rats, infected with lymphocytic choriomeningitis virus (LCMV) as neonates,
      manifest a gradual loss of hippocampal dentate granule cells and neuronal
      hyperexcitability. The current data demonstrate that GABAergic interneurons are
      dual immunostained for LCMV antigens prior to the loss of dentate granule cells,
      supporting the hypothesis that LCMV may disrupt developing inhibitory circuits
      causing unbalanced excitatory neurotransmission and the eventual death of dentate
      granule cells due to excitotoxicity.

PMID- 10943700
TI  - Genetic analysis of the alpha2-macroglobulin gene in early- and late-onset
      Parkinson's disease.
AB  - Recent association studies investigating polymorphisms in the alpha2
      macroglobulin (A2M) gene provided evidence for an involvement of this protease
      inhibitor in the pathogenesis of Alzheimer's disease (AD). The partially
      overlapping pathology between AD and Parkinson's disease (PD) led us to
      investigate the role of A2M in PD. We performed association studies in a large
      sample of 328 German PD patients and 322 closely matched healthy controls.
      Analyzing the Val1000Ile polymorphism and a pentanucleotide deletion in the 5'
      splice site of exon 18 of the A2M gene we found an excess of homozygosity for the
      A2M deletion in early-onset PD (EOPD) patients (age at onset < 50 years) compared
      to late-onset PD (LOPD) patients (age at onset > 50 years; p = 0.008, p(p)c =
      0.064, chi2 = 7.017). Therefore our data might indicate an age at onset
      modulating effect of the homozygous A2M deletion in PD.

PMID- 10943701
TI  - Brain mechanisms for reading: the role of the superior temporal gyrus in word and
      pseudoword naming.
AB  - The purpose of this study was to test the neurological validity of a dual-route
      model of reading by asking patients, who were undergoing electrocortical
      stimulation mapping, to read words with irregular print-to-sound correspondences
      and pseudowords. Brain activation profiles were also obtained from these patients
      during an auditory and a visual word recognition task using whole-head magnetic
      source imaging. We demonstrated that reading is subserved by at least two brain
      mechanisms that are anatomically dissociable. One mechanism subserves assembled
      phonology and depends on the activity of the posterior part of the left superior
      temporal gyrus (STGp), whereas the second is responsible for addressed phonology
      and does not necessarily involve this region. The contribution of STGp to reading
      appears to be based on its specialization for phonological analysis operations,
      involved in the processing of both spoken and written language.

PMID- 10943702
TI  - Expression of connexin 31 in the developing mouse cochlea.
AB  - Connexin 31 (Cx31) mutations cause an autosomal dominant form of high-frequency
      hearing loss. The immunohistochemical localization of Cx31 in mouse cochlea was
      studied at different ages between 0 and 60 days after birth (DAB). Cx31-like
      immunoreactivity was detected in fibrocytes of spiral ligament and spiral limbus
      at 12 DAB, gradually enhanced with the increase of age and reached the adult
      pattern on 60 DAB. Immunoreactivity decreased gradually from the basal to apical
      turn in all developmental stages. The mRNA of Cx31 was also identified by RT-PCR.
      The distribution of Cx31 and connexin 26 were obviously different in the
      developing mouse cochlea. The expression and distribution of Cx31 in the
      development may explain the progressive hearing loss in human Cx31 mutations.

PMID- 10943703
TI  - Collateral sprouting from sensory and motor axons into an end to side attached
      nerve segment.
AB  - A nerve segment, sutured end-to-side (ETS) to an intact rat sciatic nerve,
      becomes invaded by regenerating axons. The origin of these fibres is
      controversial: it is debated whether or not they represent collateral sprouts
      from intact axons. Here we demonstrate by double retrograde tracing, using one
      tracer for the ETS attached segment and another for the sciatic nerve proper
      double-labelled sensory neurons in 67% of the rats receiving an ETS segments.
      Double-labelled motor neurons were observed in 11% of the rats. The results show
      that a nerve segment attached ETS to an intact nerve can induce collateral
      sprouting of both sensory and motor axons although the extent of such branching
      may vary with the experimental conditions.

PMID- 10943705
TI  - Differential gene expression of dopamine D-2 receptor subtypes in rat chromaffin
      cells and sympathetic neurons in culture.
AB  - Chromaffin cells and sympathetic neurons arise from a common bipotential
      progenitor which, if exposed to nerve growth factor (NGF), matures into a
      sympathetic neuron, but if exposed to glucocorticoids (GCs), differentiates into
      a mature chromaffin cell. Pharmacological evidence indicates that, in adrenal
      medulla and sympathetic neurons, dopamine (DA) receptors belonging to the D-2
      family inhibit catecholamine secretion. The molecular characterization of these
      receptors, however, is not been yet described. Our data suggest that bipotential
      cells obtained from newborn rat adrenal medulla express both isoforms of the D-2
      receptor, while D-3 receptor and D-4 receptor messenger RNAs (mRNAs) are not
      present. GC-mediated maturation induces the expression of D-4 receptors, without
      modification of D-2 isoforms. Sympathetic neurons differentiated in vitro
      selectively express the D-2short mRNA. Taken together, present results suggest
      that NGF and GCs play a role in regulating D-2 family receptor expression in
      neural crest-derived cells.

PMID- 10943704
TI  - Magnetic source imaging of tactile input shows task-independent attention effects
      in SII.
AB  - We investigated whether attention to different stimulus attributes (location,
      intensity) has different effects on the activity of the secondary (SII)
      somatosensory cortex. Tactile stimuli were applied to the left index finger and
      somatosensory evoked fields (SEFs) were recorded using a whole-head
      magnetoencephalography (MEG) system. Two oddball paradigms with stimuli varying
      in location or intensity were performed in an ignore and an attend condition.
      Brain sources were estimated by magnetic source imaging. No attention effect was
      observed for the primary SI area. However, attention enhanced SII activity
      bilaterally from 55 to 130 ms by 52% in the spatial and 64% in the intensity
      discrimination task. SII attentional enhancement was very similar in both
      paradigms and occurred both for deviants and standards.

PMID- 10943706
TI  - Tau pathology in diffuse neurofibrillary tangles with calcification (DNTC):
      biochemical and immunohistochemical investigation.
AB  - Diffuse neurofibrillary tangles with calcification (DNTC) represents a primary
      and sporadic presenile dementia that is characterized by temporal or fronto
      temporal atrophy with diffuse neurofibrillary tangles (NFTs), neuropil threads
      and Fahr-type calcification without senile plaques. We examined the tau pathology
      in five autopsy cases of DNTC by immunoblotting and immunohistochemistry using
      phosphorylation-dependent and -independent anti-tau antibodies. The pattern of
      staining for different epitopes of beta-amyloid (A beta) was also investigated.
      NFTs were immunopositive with all the anti-tau antibodies used in this study. On
      the immunoblots, sarkosyl-insoluble tau appeared as three major bands of 60, 64
      and 68 kDa, and as a minor band at 72 kDa. The majority of extracellular NFTs
      were weakly immunopositive only with the antibody recognizing the 40 carboxyl
      terminal of A beta in DNTC. These results suggest that Alzheimer's disease-like
      tau pathology could exist independently of A beta deposits in DNTC.

PMID- 10943707
TI  - Testosterone-dependent plasticity of avian forebrain neurons is not restricted to
      the song control system.
AB  - Testosterone is acting on brain areas involved in the control of sexual
      behaviour, for example the preoptic area and the song system. We now demonstrate
      that it also affects other avian brain areas, as exemplified here by measurement
      of spine densities. Depletion of testosterone by castration or application of
      cyproterone acetate leads to a decrease in spine density in secondary sensory
      areas like lateral neo- and hyperstriatum and hyperstriatum accessorium and
      dorsale, or in associative areas such as the caudal archi- and neostriatum. We
      conclude that testosterone is acting directly on the spines, and suggest that the
      mechanism of spine density control by hormones may have arisen because of energy
      demands.

PMID- 10943708
TI  - Contextual-dependent effects of nucleus accumbens lesions on spatial learning in
      mice.
AB  - The effect of nucleus accumbens lesions on radial maze performance of C57BL/6 and
      DBA/2 mice was assessed under distinct extra-maze cuing conditions. Among sham
      lesioned mice, C57BL/6 performed better under rich than poor cuing conditions
      whereas DBA performed in the same fashion under both conditions. In C57BL/6, a
      disruptive effect of lesions was found only in mice tested under rich cuing.
      Conversely, in DBA/2, the lesions improved performance under poor cuing and
      disrupted performance under rich cuing. In that strain, a possible lesion-induced
      enhancement of attention to background stimuli improving performance under poor
      cuing but producing interference under rich cuing is suggested. In general, the
      lesions effect seemed to depend on the strain predisposition to implement
      configural or cue-based responding.

PMID- 10943709
TI  - N-acetyl-L-cysteine improves survival and preserves motor performance in an
      animal model of familial amyotrophic lateral sclerosis.
AB  - Increasing evidence implicates oxidative damage as a major mechanism in the
      pathogenesis of amyotrophic lateral sclerosis (ALS). We examined the effect of
      preventative treatment with N-acetyl-L-cysteine (NAC), an agent that reduces free
      radical damage, in transgenic mice with a superoxide dismutase (SODI) mutation
      (G93A), used as an animal model of familial ALS. NAC was administered at 1%
      concentration in the drinking water from 4-5 weeks of age. The treatment caused a
      significantly prolonged survival and delayed onset of motor impairment in G93A
      mice treated with NAC compared to control mice. These results provide further
      evidence for the involvement of free radical damage in the G93A mice, and support
      the possibility that NAC, an over-the-counter antioxidant, could be explored in
      clinical trials for ALS.

PMID- 10943710
TI  - Activation of caspase-3 in permanent and transient brain ischaemia in man.
AB  - Animal studies have shown brain ischaemia to cause oxidative damage to DNA and
      activation of caspase-3, leading to apoptosis. These changes may be exacerbated
      by reperfusion. To assess caspase-3 activation after transient and permanent
      brain ischaemia in man, we examined brain tissue from patients who had
      experienced a cardiac arrest with resuscitation or an atherothrombotic brain
      infarct, and died 12 h to 9 days later. Sections were immunostained for activated
      caspase-3 or the 89 kDa caspase-3-mediated cleavage product of poly(ADP-ribose)
      polymerase. Brain ischaemia caused activation of caspase-3 in
      macrophages/microglia. Some neurons showed delayed activation of caspase-3 after
      cardiac arrest, but very few in atherothrombotic infarcts. In man, activation of
      caspase-3 plays little part in neuronal death in atherothrombotic infarcts but
      may contribute to delayed death of neurons after cardiac arrest.

PMID- 10943711
TI  - Synaptic mechanisms of NMDA-mediated hyperpolarization in lateral amygdaloid
      projection neurons.
AB  - Synaptic mechanisms underlying NMDA-mediated responses of neurons in the guinea
      pig lateral amygdala (AL) were investigated in in vitro slice preparations. Local
      application of NMDA resulted in initial hyperpolarization of pyramidal-like spiny
      cells (projection neurons), followed by prolonged depolarization. The slow
      depolarization represented a direct postsynaptic effect of NMDA, whereas the
      initial hyperpolarization was induced presynaptically through activation of
      GABAergic interneurons and was sensitive to blockade by tetrodotoxin as well as
      the GABA(A)-receptor antagonist bicuculline. Application of NMDA resulted in AP-5
      sensitive, lasting depolarization also in putative interneurons of the AL
      suggesting direct activation of GABAergic interneurons by NMDA. These data
      indicate that interneurons in the rat lateral amygdala possess functional NMDA
      receptors, which may contribute to the predominantly inhibitory synaptic
      responses in amygdaloid neurons following activation through afferent input
      systems.

PMID- 10943712
TI  - Mitochondrial DNA deletion mutation levels are elevated in ALS brains.
AB  - This study was performed to explore the potential role of mitochondrial DNA
      mutations in the neurodegenerative process in amyotrophic lateral sclerosis
      (ALS). Using a semi-quantitative assay, a common mitochondrial DNA deletion
      mutation (mt DNA4977) was assayed in brain tissue obtained from six sporadic ALS
      patients and compared to four controls. In each brain, levels of this mutation
      were measured in a brain region affected by neurodegeneration, the motor cortex
      (Brodmann area 4), and compared to the temporal cortex (Brodmann area 17). In the
      ALS but not control brains, levels of mt DNA4977 were an average of more than 30
      fold (range 15-250) higher in Brodmann area 4. These results support and extend
      those of previous studies implying that mitochondria may participate in the
      neurodegenerative process in ALS.

PMID- 10943713
TI  - Reinforcing effects of methamphetamine in planarians.
AB  - Reinforcing properties of dopamine agonist, methamphetamine, for planarians were
      examined with the conditioned place preference (CPP) procedure. The planarians
      showed preference for the environment associated with methamphetamine
      administration. This reinforcing effect was antagonized by pretreatment with non
      selective dopamine antagonist, haloperidol. Both selective D1 antagonist SCH23390
      and selective D2 antagonist sulpiride also blocked the reinforcing effect of
      methamphetamine. These results suggest that reinforcing effects of dopaminergic
      drugs can be traced back to invertebrates such as planarians.

PMID- 10943714
TI  - Deafness induced up-regulation of GluR2/3 and NR1 in the spiral ganglion cells of
      the rat cochlea.
AB  - Expressions of AMPA (GluR2, GluR3, and GluR4) and NMDA (NR1 and NR2) glutamate
      receptors in the spiral ganglion cells of the cochlea were analyzed both at
      protein and mRNA levels in control and deaf rats between week 0 (P14) and week 8
      (P70) after deafness induced by a daily injection of kanamycin at P0-P14. In the
      deaf rats, significant up-regulations of GluR2, GluR3, and NR1 in the surviving
      spiral ganglion cells were observed, while expressions of GluR4 and NR2 were
      fairly constant. In contrast, in the control rats, the expressions of all these
      glutamate receptor subtypes were stable. These results suggest that drastic
      alterations in the diversity of GluR2/GluR3/NR1 receptor complexes in the
      surviving spiral ganglion cells, which result in alterations in Ca2+
      permeability, may contribute to the deafness-related alterations in the structure
      and function of the cochlea.

PMID- 10943715
TI  - Early signs of visual categorization for biological and non-biological stimuli in
      humans.
AB  - In a previous experiment aimed at studying gender processing from faces, we had
      found unexpected early ERP differences (45-85 ms) in task-irrelevant stimuli
      between a condition in which the stimuli of each gender were delivered in
      separate runs, and a condition in which the stimuli of both genders were mixed.
      Similar effects were observed with hand stimuli. These early ERP differences were
      tentatively related to incidental categorization processes between male and
      female stimuli. The present study was designed to test the robustness of these
      early effects for faces, and to examine whether similar effects can also be
      generated between two classes of non-biological stimuli. We replicated the
      previous findings for faces, and found similar early differential effects (50-65
      ms) for non-biological stimuli (grey and hatched geometrical shapes) only,
      however, when the two shape categories were separated by conspicuous visual
      characteristics. While these results can partly be explained by phenomena related
      to neuronal habituation in the visual cortex, they may also suggest the existence
      of coarse and automatic categorization processes for rapid distinction between
      two wide classes of stimuli with strong psychosocial significance for humans.

PMID- 10943716
TI  - Semicircular canal occlusion causes permanent VOR changes.
AB  - We measured the guinea pig horizontal vestibulo-ocular reflex (hVOR) to high
      acceleration impulsive head rotations following a unilateral lateral semicircular
      canal (LSCC) occlusion. We found a significant hVOR deficit for rotations toward
      the side of the occluded LSCC and this deficit did not show systematic changes
      over 3 months. We considered the LSCC nerve was still functional as shown by the
      normal appearance of the crista of the LSCC ampulla and also electrical
      stimulation of the LSCC. We conclude that the VOR during angular acceleration in
      response to high acceleration shows no adaptive plasticity following a unilateral
      LSCC occlusion.

PMID- 10943717
TI  - Detection of the brain response during a cognitive task using perfusion-based
      event-related functional MRI.
AB  - Event-related (ER) fMRI has evoked great interest due to the ability to depict
      the dynamic features of human brain function during various cognitive tasks. Thus
      far, all cognitive ER-fMRI studies have been based on blood oxygenation level
      dependent (BOLD) contrast techniques. Compared with BOLD-based fMRI techniques,
      perfusion-based fMRI is able to localize the region of neuronal activity more
      accurately. This report demonstrates, for the first time, the detection of the
      brain response to a cognitive task using high temporal resolution perfusion-based
      ER-fMRI. An English verb generation task was used in this study. Results show
      that perfusion-based ER-fMRI accurately depicts the activation in Broca's area.
      Average changes in regional relative cerebral blood flow reached a maximum value
      of 30.7% at approximately 6.5 s after the start of stimulation and returned to
      10% of the maximum value at approximately 12.8 s. Our results show that perfusion
      based ER-fMRI is a useful tool for cognitive neuroscience studies, providing
      comparable temporal resolution and better localization of brain function than
      BOLD ER-fMRI.

PMID- 10943718
TI  - Guanosine impairs inhibitory avoidance performance in rats.
AB  - The nucleoside guanosine, previously found to exert trophic and neuroprotective
      effects, was found to impair retention of inhibitory avoidance responses, with a
      complete effect at 7.5 mg/kg i.p. pretraining. Treated animals, when retrained 1
      week later, showed normal learning ability. Guanosine injected immediately after
      training or pretest did not alter retention latency. Combined pretraining and
      pretest treatments with guanosine failed to reverse its amnestic effect,
      excluding the contribution of state dependency. Open field parameters and shock
      sensitivity were mostly unaltered by guanosine. These results suggest an amnestic
      effect of guanosine on inhibitory avoidance in rats, in a pattern compatible with
      inhibition of glutamatergic activity. However, the mechanism for the amnestic
      effect of guanosine is yet to be elucidated.

PMID- 10943719
TI  - Enhancement of sympathetic neuron survival by synergistic action of NT3 and GDNF.
AB  - Although roles of neurotrophin-3 (NT3) and glial cell line-derived neurotrophic
      factor (GDNF) are suggested for sympathetic neuron development, survival activity
      of either NT3 or GDNF alone on cultured embryonic rat sympathetic neurons is low
      (10-20%). We demonstrate that a combination of both NT3 and GDNF exerts a
      remarkable survival activity (85%). NT3 and GDNF did not affect expression levels
      of their receptors. However, stimulation with both NT3 and GDNF caused tyrosine
      phosphorylation of Ret/GDNF-receptor at a level higher than that caused by GDNF
      alone. Furthermore, stimulation with both GDNF and NT3 induced an enhanced Thr308
      phosphorylation of Akt kinase. These results suggest that the actions of NT3 and
      GDNF converge at the Ret/GDNF-receptor to enhance survival of the developing
      sympathetic neurons through activation of the phosphatidylinositol (PI) 3
      kinase/Akt pathway.

PMID- 10943720
TI  - Increases in K+ conductance and Ca2+ influx under high glucose with suppressed
      Na+/K+-pump activity in rat myelinated nerve fibers.
AB  - To test the combined effect of high glucose and decreased Na+/K+-pump activity, a
      condition which closely mimics the diabetic state, on nerve ionic currents,
      changes in action potential and membrane current induced by high glucose in the
      presence of ouabain were investigated using voltage clamp analysis in rat single
      myelinated nerve fibers. In the presence of 0.1 mM ouabain, 30 mM glucose caused
      a progressive increase in the delayed K+ current as well as persistent decreases
      in action potential and Na+ current, suggesting that Na+/K+ pump plays an
      important role in preventing the increase in the K+ current. The latter increase
      was suppressed by a blocker of Ca2+-activated K+ channels. Two types of voltage
      dependent Ca2+ channel blockers (L and N-type) as well as a Na+/Ca2+-exchange
      blocker diminished the ouabain-induced increase in K+ conductance. These results
      suggest that high glucose with suppressed Na+/K+ pump activity might induce an
      increase of Ca2+ influx through either Ca2+ channels or reverse Na+/Ca2+
      exchange, possibly leading to the elevation of Ca2+-activated voltage-dependent
      K+ channels. Both a decrease in inward Na+ current and an increase in K+
      conductance may result in decreased nerve conduction. In addition, a possible
      increase of axoplasmic Ca2+ concentration may lead to axonal degeneration. These
      results provide a clue for understanding the pathophysiologic mechanism of
      diabetic neuropathy.

PMID- 10943721
TI  - Diazepam in the ventral striatum dissociates dopamine-dependent and dopamine
      independent place conditioning.
AB  - We have previously shown that diazepam blocks both the formation and the
      expression of amphetamine-induced conditioned place preference (CPP), but has no
      effect on the CPP induced by morphine. Because diazepam reduces dopamine activity
      in the nucleus accumbens, three experiments were conducted in order to
      investigate whether diazepam selectively blocks the expression of place
      conditioning dependent on mesolimbic dopamine. The first experiment found that
      systemic diazepam blocked the expression of conditioned place aversion induced by
      the kappa-receptor agonist U50-488. The second and third experiments demonstrated
      that intra-cranial injections of diazepam in the nucleus accumbens blocked the
      expression of amphetamine CPP but not of morphine CPP. It is concluded that
      diazepam interferes with mesolimbic dopamine-dependent motivational effects of
      drugs.

PMID- 10943722
TI  - Solubilization of PNS myelin membrane proteins by detergents.
AB  - We have applied 25 different detergents to the PNS myelin membrane. The extracts
      produced were analyzed regarding the total amount of protein solubilized, and
      which myelin glycoproteins were solubilized. The degree of protein extraction was
      correlated with the critical micelle concentration. For some detergents the
      protein extraction ability depends clearly on critical micelle concentration.
      These detergents are more potent if critical micelle concentration is small. The
      other type of extraction is independent on the critical micelle concentration,
      but extractability of proteins is low. The best detergents for solubilization of
      myelin proteins are neutral of the alkyl chain length n =9-11, as follows:
      dodecyl-beta-D-maltopyranoside, decyl-beta-D-maltopyranoside, n
      dodecylsulfobetaine. We expect that these detergents will also be suitable for
      crystallization of P0 and PASII/PMP22 glycoproteins.

PMID- 10943724
TI  - Brain regions involved in verbal or non-verbal aspects of facial emotion
      recognition.
AB  - To depict the neural substrates for facial emotion recognition and to determine
      whether their activation is confounded by a verbal factor, we studied eight
      normal volunteers with functional magnetic resonance imaging (fMRI). Verbal and
      non-verbal sample stimuli were used in a facial emotion matching task and a
      gender matching task (control condition). Compared with the gender tasks, the
      emotion tasks significantly activated the right ventral prefrontal cortex, the
      right lingual cortex, and the left lateral fusiform cortex, irrespective of
      sample stimuli. The visual association cortices showed a significant interaction
      between the task and the material presented, as the activation for verbal
      materials was higher than for non-verbal materials during the emotion matching
      tasks. By contrast, no significant interaction was found in the right ventral
      prefrontal cortex. These results suggest that the verbal factor has a different
      effect on the neural networks for facial emotion, processing.

PMID- 10943723
TI  - Expression of interleukin-6 is suppressed by inhibition of voltage-sensitive
      Na+/Ca2+ channels after cerebral ischemia.
AB  - Expression of interleukin-6 (IL-6), a neurotrophic cytokine, is up-regulated
      after cerebral ischemia, but the underlying mechanism of the up-regulation
      remains unclear. NS-7 is a novel blocker of voltage-sensitive Ca2+ and Na+
      channels and is known to reduce cerebral damage by ischemia. The present study
      was undertaken to examine the association between increases in intracellular Ca2+
      concentration induced by membrane depolarization and IL-6 induction. IL-6
      expression in rat brain was investigated by immunohistochemistry and Western blot
      analysis following 3.5-48 h of reperfusion after 1.5 h of occlusion of the middle
      cerebral artery. NS-7 (1 mg/kg; NS-7 group) or saline (saline group) was injected
      i.v. 5 min after the start of reperfusion. The saline group showed clear IL-6
      expression in various cortical regions, which peaked at 24 h of reperfusion. By
      contrast, IL-6 expression was significantly suppressed in the NS-7 group
      throughout the reperfusion period. Microglia activation was also reduced in the
      NS-7 group. These findings suggest that IL-6 expression may be up-regulated by
      the increased intracellular Ca2+ concentration triggered by membrane
      depolarization after cerebral ischemia.

PMID- 10943726
TI  - Gender differences in the functional organization of the brain for working
      memory.
AB  - Gender differences in brain activation during working memory tasks were examined
      with fMRI. Seventeen right-handed subjects (nine males, eight females) were
      studied with four different verbal working memory tasks of varying difficulty
      using whole brain echo-planar fMRI. Consistent with prior studies, we observed
      activation of the lateral prefrontal cortices (LPFC), the parietal cortices (PC),
      and additionally, caudate activation in both sexes. The volume of activated brain
      tissue increased with increasing task difficulty. For all four tasks, the male
      subjects showed bilateral activation or right-sided dominance (LPFC, PC and
      caudate), whereas females showed activation predominantly in the left hemisphere.
      The task performance data demonstrated higher accuracy and slightly slower
      reaction times for the female subjects. Our results show a highly significant (p
      < 0.001) gender differences in the functional organization of the brain for
      working memory. These gender-specific differences in functional organization of
      the brain may be due to gender-differences in problem solving strategies or the
      neurodevelopment. Therefore, gender matching or stratification is required for
      studies of brain function using imaging techniques.

PMID- 10943725
TI  - Blockade of cyclic AMP-responsive element DNA binding in the brain of CREB
      delta/alpha mutant mice.
AB  - The cAMP-responsive element binding protein (CREB) gene transcription factor has
      been implicated in the synaptic plasticity and memory. Here, we investigated the
      mechanisms of CREB and/or cyclic AMP-responsive element modulatory protein (CREM)
      binding to CRE sites in brain tissues. CRE-DNA binding was determined in nuclear
      extracts obtained from the several brain structures of wild-type and CREB
      delta/alpha mutant mice. It was found that antibodies to CREB, phosphorylated
      CREB, and CREM supershifted the CRE-DNA binding complex in cortical nuclear
      extracts from wild-type mice, which suggests that the CRE-DNA binding complex
      contains both CREB and CREM proteins. In contrast, CRE-DNA binding is abolished
      in the cortex, hippocampus, cerebellum, and amygdala of CREB delta/alpha mutant
      mice. Because the CREB delta and alpha isoforms have been deleted in CREB mutant
      mice, consequently, other forms of CREB, such as CREB-beta and CREM, are up
      regulated. These results suggest that the binding of CREM to CRE sites requires
      the presence of CREB delta/alpha, and that CREB-beta may be inefficient in
      binding to CRE-sites. Thus, these results indicate that CREB delta/alpha mutant
      mice are a useful animal model for studying the functional role of CREB-dependent
      gene expression.

PMID- 10943727
TI  - Cell activation and inflammatory response following traumatic axonal injury in
      the rat.
AB  - In a rat model of traumatic brain injury cell activation was characterized
      immunohistochemically from 2 h up to 2 weeks. Reactive astrocytosis became
      apparent perivascularly and in the grey matter within 4h after trauma. Increased
      OX42 immunoreactivity indicated microglial activation in cortex and hippocampus
      as early as 4 h, whereas up-regulation of MHC class II (OX6) was evident in white
      matter tracts at 24 h. Although macrophage (ED1) numbers increased in the
      meninges and perivascularly, brain infiltration appeared marginal. Accumulation
      of lymphocytes and granulocytes was not observed. Our results show that traumatic
      axonal injury induces a rapid and sustained glial activation in the absence of
      leukocyte infiltration. Thus, cell activation following diffuse trauma strongly
      differs from that found after focal brain damage, awaiting further functional
      characterization.

PMID- 10943728
TI  - Striatal A2A adenosine receptor antagonism differentially modifies striatal
      glutamate outflow in vivo in young and aged rats.
AB  - The effect of the adenosine A2A receptor antagonist SCH 58261 on glutamate
      release was investigated in the striatum of young and old rats by microdialysis
      experiments. SCH 58261 (50 nM) significantly decreased the spontaneous and K+
      evoked glutamate outflow in young rats. In aged rats, spontaneous glutamate
      outflow was significantly reduced in comparison to young rats and SCH 58261
      significantly increased spontaneous and K+-evoked glutamate outflow. It is
      suggested that the opposite effects of the A2A antagonist on glutamate outflow in
      young and aged rats can be respectively attributed to blockade of striatal A2A
      adenosine receptors located on glutamatergic terminals and on the striatal
      indirect output pathway.

PMID- 10943729
TI  - Different neurorescue profiles of selegiline and p-fluoro-selegiline in gerbils.
AB  - The neuroprotective/neuronal rescue effects of selegiline are not exactly
      understood, and show great variability in clinical trials. In this study, the
      dose-dependence of neuronal rescue potency of selegiline and its analogue para
      fluoro-selegiline (PFS) was investigated in gerbils. The compounds were tested in
      a transient global cerebral ischemia model. Selegiline expressed a bell-shaped,
      dose-response curve with high intrinsic activity (with greatest effect at 0.001
      mg/kg), as opposed to PFS which shows a saturation profile. These findings
      indicate possible therapeutic differences between PFS and selegiline in the
      treatment of neurodegenerative disorders. Inhibition of progression of the
      disease (neuroprotective effect) and improvements of symptoms (MAO-B inhibition)
      may occur at the same dose level using PFS, while these doses are separated in
      case of selegiline.

PMID- 10943730
TI  - Sulcogyral variation in NMDA receptor 2A/B subunit immunoreactivity in human
      brain.
AB  - NMDA receptors (NR) are important in many neurological processes. Using a large
      series of human brain tissue, we show that the distribution of NR2A/B
      immunoreactivity varies according to position along a gyrus. For pyramidal
      neurons in laminae II and III, immunoreactivity is most marked at gyral crown and
      gyral lips, diminishes along sulcal wall, and is barely detectable in sulcal
      floor cortex. In contrast, in some cases, immunoreactivity in laminae V and VI
      pyramidal neurons shows the reverse pattern. Neurofilament and calretinin
      immunoreactivity do not show this phenomenon. The findings suggest novel
      functional regionalization at the sulcogyral level in normal human brain.

PMID- 10943731
TI  - Propofol narcosis dissociates human intrathalamic and cortical high-frequency (>
      400 hz) SEP components.
AB  - Human somatosensory evoked potentials (SEP) contain a brief burst of high
      frequency wavelets (>400 Hz) presumably reflecting rapidly repeated population
      spikes of as-yet undetermined origin. To study state-dependent response changes,
      SEP after electric median nerve stimulation were recorded in six Parkinson's
      disease patients perioperatively from intrathalamic electrode implants, and in
      five non-implanted patients from scalp electrodes, before and under propofol
      narcosis. In all intrathalamic recordings burst amplitude and intraburst
      frequency (approximately 950 Hz) proved to be almost stable under propofol
      administration. In strong contrast, the scalp burst (640 Hz) was significantly
      slowed (480 Hz) under propofol narcosis, and its amplitude reduced to 28% of the
      pre-propofol baseline. Low-frequency SEP components which underly the burst at
      thalamic (P16) and cortical level (N20) did not change significantly. This
      dissociation of bursts indicates neuronal generators showing different
      sensitivities to propofol narcosis, with a robust thalamic response and a state
      dependent cortical contribution, possibly from pyramidal chattering cells and/or
      inhibitory interneurons.

PMID- 10943732
TI  - Secretory activity and serotonin innervation of lizard's subcommissural organ.
AB  - We investigated immunohistochemically the subcommissural organ (SCO) glycoprotein
      secretion, its serotoninergic (5-HT) innervation and the possible control of this
      innervation upon the SCO activity in lizards (Agama impalearis, Saurodactylus
      mauritanicus and Eumeces algeriensis). Inside the SCO, interspecific differences
      in the intensity and the distribution of both secretory product and 5-HT nerve
      fibers were observed. Compared with Agama and Eumeces, the SCO of Saurodactylus
      displayed intense secretory products and several 5-HT fibers. In Saurodactylus,
      i.p. injection of parachlorophenylalanine, a potent inhibitor of 5-HT synthesis,
      produced a marked decrease of SCO secretory product. We report in this study
      species differences of the lizard SCO secretory activity and its possible
      physiological control by 5-HT innervation, as previously demonstrated in mammals.

PMID- 10943733
TI  - Age-related changes in bone mineral density and serum bone-related proteins in
      premenopausal and postmenopausal Japanese women.
AB  - The purpose of this cross-sectional study was to characterize the age-related
      change in bone metabolism during the pre- and postmenopausal periods, and to
      define the standard levels of three serum markers of bone metabolism,
      pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP),
      carboxyterminal propeptide of type I procollagen (PICP), and bone gla protein
      (BGP), in Japanese adult women. The bone mineral density (BMD) of the lumbar
      spine (L2-L4) and the serum levels of ICTP, PICP and BGP were determined in a
      total of 207 healthy Japanese women (108 premenopausal and 99 postmenopausal).
      The lumbar BMD decreased significantly with increasing age not only in
      postmenopausal women (P<0.001) but also in premenopausal women (P=0.014). There
      was a clear gap in the serum levels of ICTP, PICP and BGP between the
      premenopausal and postmenopausal group (P<0.001), but those were absolutely the
      same within each group except for ICTP in the postmenopausal women. These
      findings and the values of serum ICTP, PICP and BGP in pre- and postmenopausal
      women obtained in this study are expected to be very useful for treatment of
      postmenopausal osteoporosis.

PMID- 10943734
TI  - Growth hormone directly stimulates testosterone and oestradiol secretion by rat
      Leydig cells in vitro and modulates the effects of LH and T3.
AB  - The modulatory effect of GH on basal, LH and T3 mediated secretion of
      testosterone and oestradiol by purified rat (60 day old) Leydig cells was studied
      in vitro. Percoll gradient purified Leydig cells (1 x 10(3)) were cultured for 48
      hours at 34 degrees C in a medium containing different concentrations of rat GH
      (5-400 ng/mL), after an initial culture for 24 hours at 37 degrees C. GH
      increased testosterone and oestradiol secretions in a dose dependent manner.
      While testosterone secretion reached the saturation point with 50 ng GH,
      oestradiol secretion reached the saturation point with 150 ng GH, followed by
      diminished secretions. Co-administration of minimum (10 ng) effective does of GH
      with minimum (25 ng) or maximum (100 ng) effective doses of oLH significantly
      decreased the testosterone secretion. However, an increased secretion of
      testosterone was observed when maximum effective doses of rGH (50 ng) and oLH
      (100 ng) were co-administered. Minimum effective (25 ng) or maximum effective (50
      ng) doses of T3 inhibited GH mediated secretion of testosterone in vitro.
      Oestradiol concentration in the culture medium increased when either dose of rGH
      was co-administered with the minimum or maximum effective doses of oLH. T3 50 ng
      augmented the secretion of oestradiol by Leydig cells in the presence of GH.
      These results indicate that GH acts as a gonadotrophin to stimulate testosterone
      and oestradiol secretions by Leydig cells, and that it modulates LH or T3 induced
      secretion of these steroids, depending on the intensity of their stimulation.

PMID- 10943735
TI  - A case of renin-producing adrenocortical cancer.
AB  - Here we report a case of a renin-producing adrenocortical carcinoma. A 57-year
      old woman was referred to our hospital complaining of thirst and generalized
      muscle weakness. She was diagnosed as being hypertensive and diabetic with
      associated hypokalemia and she had a hard elastic mass with a diameter of 10 cm
      on the left side of her neck. An abdominal computed tomography scan revealed a
      suprarenal mass on the left side (8.5 x 8 x 6.5 cm). Endocrinological examination
      demonstrated a marked elevation in the patient's serum glucocorticoid and sex
      steroid hormones as well as plasma renin activity. Histological examination of a
      sample taken from the neck mass revealed a metastasis from an adrenal carcinoma,
      which was stained positively with antibodies against cytochrome P450 and renin,
      establishing the diagnosis of a renin-producing adrenocortical carcinoma.
      Trilostane was effective in reducing serum cortisol levels, but mitotane was
      ineffective.

PMID- 10943736
TI  - Accumulation of identical T cell clones in the right and left lobes of the
      thyroid gland in patients with Graves' disease: analysis of T cell clonotype in
      vivo.
AB  - To elucidate the involvement of intrathyroidal T cells in the thyroid antigen
      specific immune response in Graves' disease (GD), we investigated whether
      identical T cell clonotypes accumulate clonally in the right and left lobes of
      thyroid glands of GD patients. mRNAs extracted from thyroid glands of five
      females patients with GD were reverse-transcribed to cDNA and then the genes
      coding the T cell receptor B chain variable (V-NDN-J) region were amplified using
      polymerase chain reaction. Single strand conformation polymorphism analysis and
      subsequently nucleotide sequencing were also performed to determine the clonotype
      of accumulating T cells. T cells infiltrating the thyroid glands showed
      oligoclonal expansion. The expanded T cell clonotypes were not detected in
      peripheral blood of the same patients. Importantly, the majority of expanding T
      cell clonotypes in the two lobes of the thyroid glands were identical. Our
      findings suggest that the clonal expansion of identical T cell clonotypes in the
      two lobes is driven by factors common to both lobes, such as thyroid-specific
      antigens, in patients with Graves' disease.

PMID- 10943737
TI  - Analysis of possible silencer elements of ovine interferon-tau gene.
AB  - During the peri-implantation period significant production of ovine interferon
      tau (olFNtau) by the trophectoderm is detected in day 13-16 conceptuses, but its
      level rapidly declines thereafter. To understand molecular mechanisms by which
      oIFNtau gene expression is down-regulated, a variety of deletion constructs were
      prepared from upstream sequences of the oIFNtau gene and examined for possible
      silencer regions by using transient transfection into human choriocarcinoma,
      JEG3, cells. Two regions between -700 to -654 bases (distal region) and from -503
      to -453 bases (proximal region) were found to be the possible negative regulatory
      regions. With probes prepared from these regions, gel mobility shift assay (GMSA)
      was then conducted. DNA-protein complexes were observed, but the gel shift
      pattern was different between nuclear extracts from days 14 (active oIFNtau
      production) and 20 (minute oIFNtau production) ovine trophoblasts. Day 20 nuclear
      extracts exhibited more band patterns than those of day 14; most notably the
      distal region between -692 and -668 bases exhibited the distinct band with
      nuclear extracts from day 20, but not from day 14 trophoblasts. In addition, the
      band patterns from day 20 trophoblast nuclear proteins were similar to those
      detected with JEG3 and HeLa cell nuclear extracts. Taken together, these
      observations suggest that the upstream sequences identified could serve as
      negative regulatory regions to which various nuclear factors bind, resulting in
      reduction of oIFNtau gene transcription.

PMID- 10943738
TI  - Identification of somatotrophs, mammosomatotrophs, and mammotrophs by sandwich
      cell immunoblot assay in GH-secreting adenomas and prolactinomas: correlations
      between the proportions of hormone secreting cells and tumor size.
AB  - Sandwich cell immunoblot assay(sandwich CIBA) was used to identify somatotrophs
      (GH cells), mammosomatotrophs, and mammotrophs (PRL cells) in pituitary tumors
      obtained from patients with GH-secreting adenomas and prolactinomas. The mean
      serum GH level was 177.6 ng/ml in 19 patients with GH-secreting adenomas and the
      mean PRL level was 2,129 ng/ml in 9 patients with prolactinomas. GH-secreting
      adenomas could be divided into 3 groups according to the proportions of the cell
      types. The GH cell dominant type had more than 70% GH cells. The mammosomatotroph
      cell dominant type had more than 80% mammosomatotrophs. The non-dominant type had
      no dominant cell type. There was a good correlation (r2=0.804) between serum GH
      levels and tumor size in patients with the GH cell dominant type (n=10). The
      nondominant type (n=8) had a low serum level of GH except for one tumor. The
      mammosomatotroph cell dominant type (n=1) showed high serum levels of both GH and
      PRL. All prolactinomas had a predominance of PRL cells. Sandwich CIBA is a simple
      method for detecting GH cells, mammosomatotrophs, and PRL cells, and useful for
      classification for GH-secreting adenomas.

PMID- 10943739
TI  - Prevalence of GH-1 gene deletion in patients with isolated growth hormone
      deficiency in Japan. GH Gene Study Group.
AB  - A multicenter study was carried out to investigate the prevalence of growth
      hormone (GH-1) gene deletions among patients with isolated growth hormone
      deficiency (IGHD) and extremely short stature in Japan, using PCR method. Genomic
      DNA was extracted from the whole blood samples of 48 patients (34 males and 14
      females) at 20 hospitals. All the patients fulfilled the inclusion criteria as
      follows: (1) IGHD patients whose every peak serum GH level in more than two tests
      <5 ng/ml and (2) pretreatment height < -- 3SD, regardless of family history and
      facial feature characteristic of GH-1 gene deletion. The subjects were screened
      for deletions in GH-1 gene, using a PCR method that could identify deletions of
      6.7, 7.0 and 7.6 kbp. Three (6.25%) out of 48 subjects were found to have such
      deletion fragments. The first case was a boy homozygous for deletion of 6.7 kbp
      fragments. The second case was a girl heterozygous for 6.7 kbp deletion. A direct
      sequence analysis revealed a 2-bp deletion in exon 3 on the remaining allele that
      created a stop codon in exon 4. The third case was a boy also heterozygous for
      6.7 kbp deletion. By direct sequencing analysis, three point mutations were
      detected in the promoter region on the opposite allele together with a four-base
      addition at base 250. One of the mutations was in the area of Pit-1 binding site
      (at base - 123). The latter two cases apparently represent new types of compound
      heterozygote of GH-1 gene deletion. Our results suggest that GH-1 gene mutation
      is not so rare in extremely short IGHD children in Japan.

PMID- 10943740
TI  - Final height of Japanese patients with X-linked hypophosphatemic rickets: effect
      of vitamin D and phosphate therapy.
AB  - X-linked hypophosphatemic rickets (XLH) is one of the most common causes of
      rickets in infancy and childhood. Combination therapy of vitamin D and phosphate
      is generally used for patients with XLH. Effect of treatment of vitamin D and
      phosphate during childhood on final height of XLH has to be elucidated in
      Japanese. There have been only three Caucasian studies on final height of XLH
      with treatment since childhood. Purpose of this study is to report adult height
      and therapeutic effect of 22 Japanese participants (5 males, 17 females) with XLH
      who were treated with phosphate (33-200 mg/kg/day as phosphorus divided into 3 or
      4 doses) and vitamin D (vitamin D2 or 1alpha-hydroxyvitamin D3) for more than
      five years and evaluate effect of the treatment on the final height
      retrospectively. Final height (FHt) for all participants was -1.69+/-11.11 SD.
      FHt (-1.69+/-1.11 SD) was significantly higher than height at the initiation of
      treatment (-2.38+/-0.88 SD) for all participants (P<0.01). In conclusion,
      combination therapy of vitamin D and phosphate improved final height of Japanese
      patients with XLH as is similar to previous Caucasian studies.

PMID- 10943741
TI  - The role of parathyroid hormone-related protein in intra-tracheal fluid.
AB  - Parathyroid hormone-related protein (PTHrP), a multi-functional protein, is
      produced by many tissues in fetus. PTHrP concentration in amniotic fluid is
      reported to be significantly higher than in either fetal or maternal plasma.
      Other investigators have reported that PTHrP in amniotic fluid is derived mainly
      from amnion. The aim of this study was to investigate the contribution of fetus
      to PTHrP in amniotic fluid and the role of PTHrP in human fetal lung tissue.
      Samples of amniotic fluid, neonatal intra-tracheal fluid, gastric fluid, and the
      first urine of neonates were obtained at the time of elective cesarean section
      (n=11), and the concentrations of PTHrP were measured. The PTHrP level in intra
      tracheal fluid (41.0+/-19.6 pmol/l, mean+/-SD) was significantly higher than the
      levels in amniotic fluid (22.1+/-0.8), neonatal gastric fluid (13.5+/-2.5), first
      urine (0.95+/-0.6), umbilical cord venous and arterial plasma (1.35+/-0.2, 1.63+/
      0.3) and maternal plasma (1.05+/-0.1). PTHrP and PTH/PTHrP receptor mRNA were
      detected in human lung tissue obtained from a fetus stillborn at 36 weeks of
      gestation. The effects of PTHrP on fetal lung maturation were studied in H441
      cells from a human lung epithelial cell line. PTHrP (10(-7)M) significantly
      suppressed cell proliferation (p<0.05) to approximately 80% of the control level,
      while administration of PTHrP significantly increased surfactant protein A
      production (p<0.01). We first demonstrated the high concentration of PTHrP in
      intra-tracheal fluid that may suggest the positive production of this protein
      from the fetal lung. The results obtained by in vitro study using a human lung
      epithelial cell line suggest that PTHrP derived from the fetal lung might
      modulate its own maturation.

PMID- 10943742
TI  - Role of reconstituted basement membrane in human granulosa cell culture.
AB  - The effects of Matrigel, a reconstituted basement membrane, on human granulosa
      cells were investigated. Cells were obtained from follicular aspirate in the
      course of oocyte retrieval for in vitro fertilization and were cultured on either
      a surface coated with Matrigel or uncoated plastic. Light and electron microscopy
      showed that granulosa cells cultured on Matrigel demonstrated three-dimensional
      aggregated cells with well differentiated morphology: numerous lipid droplets,
      microvilli, junctional complexes and lumen-like structures were seen. In
      contrast, cells cultured on plastic were flattened, poorly differentiated and
      showed apoptotic cells. Immunocytochemistry showed that the proportion of
      immunopositive cells for 3beta-hydroxysteroid dehydrogenase was increased in
      cultures on Matrigel. The results of the present study suggest that culture on
      Matrigel promotes the differentiation of human granulosa cells and provides a
      useful tool which may improve the efficiency of in vitro fertilization.

PMID- 10943743
TI  - CT-Guided acetic acid injection therapy for aldosterone-producing adrenocortical
      adenoma: a preliminary report of three cases.
AB  - We reported the preliminary outcomes of CT-guided percutaneous injection therapy
      for aldosterone-producing adrenocortical adenoma (APA). Five sessions of
      injection therapy, 4 percutaneous acetic acid injections (PAI) and 1 percutaneous
      ethanol injection (PEI) were performed in 3 patients with APA. A small amount of
      acetic acid or ethanol solution was injected via a needle placed precisely inside
      the tumor. The procedure was frequently monitored by repetitive CT scanning. The
      follow-up period ranged from 5 to 27 months. After the treatment, hypertension
      was normalized or controlled by a low dose of conventional anti-hypertensive
      drug. In 2 of 3 cases the plasma aldosterone levels were normalized. Although
      temporary symptoms of alcoholic intoxication were observed in the single session
      of PEI, the 4 sessions of PAI were associated with no adverse symptoms or
      complications. Although this study covers only short-term results in 3 patients,
      CT-guided PAI appears to be a safe and effective treatment and may be a promising
      alternative as a simple and far less invasive therapy for APA.

PMID- 10943744
TI  - Hyperthyroid Graves' disease after hemithyroidectomy for papillary carcinoma:
      report of three cases.
AB  - Here we report three cases of hyperthyroid Graves' disease that occurred after
      partial thyroidectomy for papillary carcinoma. In Case 1, the patient first
      developed hyperthyroidism 2 years after resection of left thyroid lobe, was
      treated for 2 years with antithyroid drug which was then discontinued, and
      relapsed with periodic paralysis after 8 years of remission. In Case 2, a
      hyperfunctioning remnant thyroid was noted 22 years after right
      hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks
      after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid
      microsome were positive in preoperative serum, in line with a report by others
      detecting these antibodies in 2 out of 3 such cases examined. Later bioassay
      revealed activity of thyroid stimulating antibodies in that serum, with further
      increase in titer in the sample taken at the clinical manifestation. Hence in
      Case 3, surgical stress may have altered immunological homeostasis, promoting a
      preclinical Graves' disease to full-blown hyperthyroidism.

PMID- 10943745
TI  - Thyroid-stimulating antibody in a patient with euthyroid Graves' disease.
AB  - We report an 11-year-old girl with euthyroid Graves' disease. She was referred to
      our clinic because of left exophthalmos without other symptoms suggestive of
      hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free
      triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was
      below normal and impaired TSH response to TSH releasing hormone (TRH) was found.
      Although the sera were positive for anti-TSH receptor antibody (TRAb) and thyroid
      stimulating antibody (TSAb), both titers were not as high as usually observed in
      Graves' disease. Three months later, she developed hyperthyroidism and was
      treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all
      symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb
      was negative though TSAb remained positive. TSAb is therefore a good indicator to
      use in the diagnosis and follow-up of euthyroid Graves' disease and should be
      measured in patients with exophthalmos of unknown origin, even in children.

PMID- 10943746
TI  - Association of Takayasu's disease and autoimmune gestational diabetes mellitus.

PMID- 10943747
TI  - A medical/vocational case coordination system for persons with brain injury: an
      evaluation of employment outcomes.
AB  - OBJECTIVE: To evaluate initial placement and 1-year employment outcomes of a
      Medical/Vocational Case Coordination System (MVCCS) for persons with brain injury
      (BI) that provides: (1) early case identification and coordination, (2)
      appropriate medical and vocational rehabilitation interventions, (3) work trials,
      and (4) supported employment interventions including job coaching. PARTICIPANTS:
      One hundred fourteen Minnesota residents, ages 18 to 65 years, with acquired BI.
      MAIN OUTCOME MEASURES:  OUTCOME: Five levels of Vocational Independence Scale
      (VIS). PREDICTOR: Preinjury employment status (VIS) and years of education,
      severity of initial injury, time since injury, current impairment/disability as
      measured by the Rasch-analyzed Staff Mayo-Portland Adaptability Inventory (MPAI),
      and impaired self-awareness measured by staff rating and the difference between
      Staff MPAI and Survivor MPAI. RESULTS: At placement, 46% in independent work; 25%
      in transitional placements; 9% in long-term supported employment; 10% in
      sheltered work; and 10% not placed. At 1-year follow-up (n = 101), 53% in
      independent work; 19% in transitional placement; 9% in supported work; 6% in
      sheltered work; and 13% unemployed. Regression analyses showed time since injury
      and Rasch Staff MPAI predicted VIS at placement; only VIS at placement
      independently predicted VIS at 1-year follow-up; Rasch Staff MPAI and preinjury
      education level predicted time to placement. CONCLUSIONS: The MVCCS optimized
      vocational outcome after BI. Time since injury and impairment/disability best
      predicted vocational placement. Level of initial placement best predicted
      employment status at follow-up. Persons with greater disability required more
      extended time and more extensive rehabilitation services before placement.

PMID- 10943748
TI  - Inhibition of the triceps surae stretch reflex by stimulation of the deep
      peroneal nerve in persons with spastic stroke.
AB  - OBJECTIVE: To reduce the triceps surae stretch reflex by electrical stimulation
      of the deep peroneal nerve. DESIGN: Intervention study. SETTING: Research
      institution. PARTICIPANTS: Sample of convenience of 10 spastic stroke
      individuals. INTERVENTION: After the deep peroneal nerve was stimulated between
      0.9 and 4 times tibialis anterior motor threshold, the triceps surae was
      stretched to elicit a reflex. MAIN OUTCOME MEASURE: The triceps surae stretch
      reflex was quantified by the amplitude of the reflex electromyography (EMG) in
      soleus and medial gastrocnemius muscles and mean ankle moment. Paired t test and
      the Wilcoxon signed rank test (p < .05) were used to evaluate the effect of
      conditioning stimulation. RESULTS: The soleus stretch reflex EMG was reduced
      significantly (p < .001) by stimulating the deep peroneal nerve to 25%+/-6%
      (standard error) of the unconditioned value (relaxed triceps surae). The optimal
      interval between stimulation and stretch was 141+/-15 msec. The velocity
      threshold increased significantly (p = .006) from a median value of 8 degrees per
      second to 33 degrees per second and the area under the stretch velocity/stretch
      reflex relation decreased significantly (p < .001) (soleus EMG). CONCLUSIONS: The
      stretch reflex of relaxed triceps surae in persons with spastic stroke can be
      extensively reduced by stimulating the deep peroneal nerve at several times motor
      threshold of the tibialis anterior.

PMID- 10943749
TI  - Functional outcome in stroke patients with atrial fibrillation.
AB  - OBJECTIVES: To identify the prevalence of atrial fibrillation (AF) in a sample of
      stroke patients and to evaluate the impact of AF on patient clinical
      characteristics and functional outcome. DESIGN: A retrospective case-comparison
      study. SETTING: University-affiliated rehabilitation centers. PARTICIPANTS: One
      hundred ninety-six of 231 consecutive stroke patients admitted to inpatient
      rehabilitation units were evaluated during the rehabilitation period. MAIN
      OUTCOME MEASURES: Characteristics of cerebral lesions, patient demographic
      features, disease duration, length of hospital stay (LOS), risk factors for
      stroke, and functional status at admission and at discharge were assessed and
      compared in patients with and without AF. Functional Independence Measure (FIM)
      and Adapted Patient Evaluation Conference System (APECS) were used to evaluate
      functional status. RESULTS: AF was diagnosed in 41 (20.1%) patients. Patients who
      had AF were more likely to have ischemic cerebral lesions. There were no
      significant differences between the AF and non-AF groups with regard to mean age,
      LOS, and disease duration. Ischemic and valvular heart disease were more common
      in patients with AF. Based on FIM and APECS scores, both initial and discharge
      disability were more severe in patients with AF. In a multivariate model, AF was
      a negative prognostic factor for functional outcome in stroke patients.
      CONCLUSION: AF is not only associated with increased risk of stroke, but also
      with markedly greater disability in stroke patients. Factors such as size and
      type of cerebral lesions, stroke severity, comorbid conditions, and impact of AF
      on systemic and cerebral circulation can influence stroke recovery.

PMID- 10943750
TI  - Clinical predictors of dysphagia and aspiration risk: outcome measures in acute
      stroke patients.
AB  - OBJECTIVE: To use an established dysphagia clinical screening system to evaluate
      outcomes in acute stroke patients. DESIGN: Case-control study. SETTING: Tertiary
      care center. PARTICIPANTS: Acute stroke patients (n = 56) consecutively referred
      to a speech pathology service. MAIN OUTCOME MEASURES: Outcomes (ie, pneumonia,
      dietary status at discharge) in patients who were referred for a
      videofluoroscopic swallow study (VSS) based on results of a previously validated
      clinical screening system were compared with outcomes in patients who were not
      referred for VSS based on the clinical evaluation. RESULTS: Thirty-eight of 56
      patients (68%) presented with 2 or more clinical predictors of moderate to severe
      dysphagia and were further evaluated with VSS, whereas 18 patients (32%) had
      fewer than 2 clinical features and were not evaluated radiographically. Based on
      patient outcomes and VSS results, identification of at least 2 clinical
      predictors significantly distinguished patients with moderate to severe dysphagia
      from patients with mild dysphagia or normal swallowing. None of the patients in
      either group developed pneumonia while following recommendations of the clinical
      or dynamic swallowing evaluation, and 93% of the patients returned to a regular
      diet. CONCLUSIONS: These data demonstrate that clinical use of this screening
      system can objectively identify acute stroke patients who warrant further
      diagnostic studies and can safely determine which patients need no further
      deglutitive evaluation.

PMID- 10943751
TI  - Validation of the Frenchay Activities Index in a general population aged 16 years
      and older.
AB  - OBJECTIVES: To assess the validity and reliability of the Frenchay Activities
      Index (FAI) and to establish age and sex norms in people at or over the age of 16
      years. DESIGN AND SETTING: Postal questionnaire survey to 1280 people randomly
      selected from 8 Health Authority patient registers in England. MAIN OUTCOME
      MEASURES: FAI scores, subscale scores by age and sex, health status, perceived
      level of activity, and subjects' opinions on how well the FAI reflected their
      activities. Test-retest reliability was measured in 1 Health Authority. RESULTS:
      The response rate was 49%. Men scored lower than women overall and on the
      domestic activities subscale. Respondents between the ages of 16 and 24 years and
      those over 85 years had the lowest FAI scores. FAI scores were related to self
      reported health status, self-reported levels of activity, and presence of long
      standing illness/disability. The FAI has high test-retest reliability.
      Qualitative data suggested that items such as sport, physical exercise, and
      caring for children should be included to make the FAI suitable for a wider age
      range. CONCLUSION: The FAI has good construct validity, particularly in middle
      aged and elderly people, and is reliable. For the FAI to be valid in nonstroke
      populations, items specific to younger people must be incorporated into it. We
      have established preliminary age and sex norms that should be interpreted with
      caution, given the low response rate.

PMID- 10943752
TI  - Chronic phantom sensations, phantom pain, residual limb pain, and other regional
      pain after lower limb amputation.
AB  - OBJECTIVES: To determine the characteristics of phantom limb sensation, phantom
      limb pain, and residual limb pain, and to evaluate pain-related disability
      associated with phantom limb pain. DESIGN: Retrospective, cross-sectional survey.
      Six or more months after lower limb amputation, participants (n = 255) completed
      an amputation pain questionnaire that included several standardized pain
      measures. SETTING: Community-based survey from clinical databases. PARTICIPANTS:
      A community-based sample of persons with lower limb amputations. MAIN OUTCOME
      MEASURES: Frequency, duration, intensity, and quality of phantom limb and
      residual limb pain, and pain-related disability as measured by the Chronic Pain
      Grade. RESULTS: Of the respondents, 79% reported phantom limb sensations, 72%
      reported phantom limb pain, and 74% reported residual limb pain. Many described
      their phantom limb and residual limb pain as episodic and not particularly
      bothersome. Most participants with phantom limb pain were classified into the two
      low pain-related disability categories: grade I, low disability/low pain
      intensity (47%) or grade II, low disability/high pain intensity (28%). Many
      participants reported having pain in other anatomic locations, including the back
      (52%). CONCLUSIONS: Phantom limb and residual limb pain are common after a lower
      limb amputation. For most, the pain is episodic and not particularly disabling.
      However, for a notable subset, the pain may be quite disabling. Pain after
      amputation should be viewed from a broad perspective that considers other
      anatomic sites as well as the impact of pain on functioning.

PMID- 10943753
TI  - Complications of fluoroscopically guided transforaminal lumbar epidural
      injections.
AB  - OBJECTIVES: To assess the incidence of complications of fluoroscopically guided
      lumbar transforaminal epidural injections. DESIGN: A retrospective cohort design
      study. Patients presenting with radiculopathy, caused by either lumbar spinal
      stenosis or herniated nucleus pulposus confirmed by magnetic resonance imaging or
      computed tomography scanning, received transforaminal epidural steroid injections
      as part of a conservative care treatment plan. SETTING: A multidisciplinary spine
      care center. INTERVENTION: All injections were performed consecutively over a 4
      month period by five physiatrists. An independent observer reviewed medical
      charts, which included a 24-hour postprocedure telephone call by an ambulatory
      surgery center nurse who had asked a standardized questionnaire about
      complications following the injections. Physician follow-up office notes 1 to 3
      weeks after the injection, along with epiduragrams, were also reviewed. RESULTS:
      Two hundred seven patients who received 322 injections were reviewed.
      Complications per injection seen included 10 transient nonpositional headaches
      that resolved within 24 hours (3.1%), 8 increased back pain (2.4%), 2 increased
      leg pain (0.6%), 4 facial flushing (1.2%), 1 vasovagal reaction (0.3%), 1
      increased blood sugar (258 mg/dL) in an insulin-dependent diabetic (0.3%), and 1
      intraoperative hypertension (0.3%). No dural punctures occurred. CONCLUSIONS:
      There were no major complications. The incidence of minor complications was 9.6%
      per injection. All reactions resolved without morbidity, and no patient required
      hospitalization.

PMID- 10943754
TI  - Rehabilitation of neck-shoulder pain in women industrial workers: a randomized
      trial comparing isometric shoulder endurance training with isometric shoulder
      strength training.
AB  - OBJECTIVES: To study whether isometric shoulder endurance was more advantageous
      than isometric shoulder strength training in reducing pain and perceived exertion
      and to increase shoulder function through improved muscle endurance and strength.
      DESIGN: Randomized trial. SETTING: Three occupational health care centers.
      PARTICIPANTS: Women industrial workers with nonspecific neck-shoulder pain. The
      International Classification of Diseases, 10th Revision (ICD-10) diagnosis was
      "cervicobrachial syndrome" (M53.1). Thirty-eight patients completed the isometric
      shoulder endurance training and 31 patients completed the isometric shoulder
      strength training. INTERVENTION: Twelve weeks of training. MAIN OUTCOME MEASURES:
      Self-reported pain and rating of perceived exertion (RPE), arm motion performance
      test, shoulder muscle strength, shoulder muscle endurance, and shoulder
      functional tests, as well as follow-up after supervised training had ended.
      RESULTS: The isometric shoulder strength training resulted in an almost one-scale
      step decrease in RPE at work and a 5% to 15% improvement of arm motion
      performance compared with the endurance training. The isometric shoulder strength
      training more effectively improved left side shoulder abduction strength (p <
      .026), but no major differences were found for the other strength measurements.
      The isometric shoulder endurance training was not more successful than the
      strength training in the endurance test (p .51 to .81). CONCLUSIONS: Physical
      training programs for neck-shoulder pain may include isometric shoulder muscular
      strength exercise in addition to isometric shoulder endurance training, rather
      than endurance training only.

PMID- 10943755
TI  - Changes in strength over time among polio survivors.
AB  - OBJECTIVE: To study changes in the strength of different muscle groups in polio
      survivors over a period of approximately 9 months. DESIGN: Longitudinal study.
      SETTING: Moss Rehabilitation Research Institute. PARTICIPANTS: One hundred twenty
      subjects (57 men, 63 women) were studied on three occasions, each 3 to 5 months
      apart. Subjects were recruited through the Einstein-Moss Post-Polio Management
      Program. newspaper advertisements, and polio support groups. MAIN OUTCOME
      MEASURES: Isometric strength of 30 muscle groups (16 in upper extremities, 14 in
      lower extremities) was measured, using a hand-held dynamometer. RESULTS: Data
      were analyzed in two separate groups: upper-extremity muscles and lower-extremity
      muscles. Results for the upper-extremity muscles revealed evidence of a
      significant deterioration in strength. The amount of deterioration differed among
      muscles and increased with age. There was also evidence of deterioration in
      strength in the flexor muscles in the ankle, hip, and knee. However, the rate of
      deterioration in these muscles was not strongly related to age, time since polio,
      gender, symptom status, or history of residual weakness. CONCLUSIONS: Strength is
      deteriorating among polio survivors at a rate higher than that associated with
      normal aging. This deterioration is not occurring in the extensor, or so-called
      "weight-bearing" muscles, but is occurring in many of the upper-extremity muscle
      groups and in the flexor muscles in the lower extremities.

PMID- 10943756
TI  - Inspiratory muscle training in patients with prior polio who use part-time
      assisted ventilation.
AB  - OBJECTIVE: To evaluate whether inspiratory muscle training in patients with prior
      poliomyelitis (and with symptoms and signs of hypoventilation) who use part-time
      assisted ventilation could improve symptoms and respiratory muscle function
      without adverse effects. DESIGN: Intervention study with before-after trial.
      SETTING: Training was performed in the patients' homes; assessments were
      performed at the hospital. PATIENTS: Ten prior-polio patients were included.
      Three of them did not complete the trial, and their data were not included in
      results of training. INTERVENTION: Ten weeks of daily inspiratory muscle
      training. MAIN OUTCOME MEASURES: Spirometry, maximal inspiratory and expiratory
      pressures, inspiratory muscle endurance, and questions regarding activities of
      daily living were performed. RESULTS: Inspiratory endurance capacity over 5
      minutes improved from 10.7 to 16.7cm H2O (p < .05) assessed at 15 on the Borg
      scale, and most patients improved in activities of daily living. The whole-body
      endurance capacity remained stable over the studied period. CONCLUSION:
      Inspiratory muscle training and close supervision can increase respiratory muscle
      endurance and improve well-being in patients with prior polio who use part-time
      assisted ventilation.

PMID- 10943757
TI  - Portable dynamometer anchoring station for measuring strength of the hip
      extensors and abductors.
AB  - OBJECTIVE: To assess the reliability of a specially designed dynamometer
      anchoring station in the measurement of hip muscle strength. DESIGN: Prospective
      study using test-retest design. SETTING: Outpatient clinic setting. PARTICIPANTS:
      Ten subjects, ages 25 to 35yrs. MAIN OUTCOME MEASURES: Using the apparatus, three
      consecutive measures were recorded for hip abduction and extension by an
      inexperienced examiner. Two weeks later, the same subjects were retested, with
      the evaluator blinded to the initial results. In both the test and retest,
      average and maximal values of strength were calculated for each muscle.
      Reliability of the device was assessed by computing the intraclass correlation
      coefficients and coefficients of variation (CVs). RESULTS: Intraclass correlation
      coefficients ranged from .94 to .98. The average CV for the maximal and average
      abduction strength had values of 4.77% and 4%, respectively. The maximal and
      average extension strength had average CV values of 8.06% and 7.83%,
      respectively. CONCLUSION: This specially designed dynamometer anchoring station
      has been found to be highly reliable in the measurement of hip girdle strength
      and has the advantage of easy adjustability and portability for large-scale
      screenings. This device enhances the reliability of the dynamometer, which may be
      subject to considerable variability when applied by hand to the powerful hip
      girdle musculature.

PMID- 10943758
TI  - A refined view of the determinants of gait: significance of heel rise.
AB  - OBJECTIVES: Although the major determinants of gait described by Saunders and
      colleagues have been accepted for more than 40 years, recent investigations raise
      the question of whether the reduction in center of mass (COM) displacement
      compared with a compass gait model indeed results from the factors originally
      described. We tested the hypothesis that heel rise at the end of stance is a true
      determinant that can explain a considerable portion of the reduction in COM
      vertical displacement during walking. DESIGN: Stereophotogrammetric data during
      walking were collected. A modified compass gait model incorporating the effect of
      heel rise, as compared with predictions based on a standard compass model, were
      used to estimate the isolated effect of heel rise on reducing the vertical
      displacement of COM. SETTING: A gait laboratory. PARTICIPANTS: Thirty able-bodied
      subjects. MAIN OUTCOME MEASURE: The estimated reduction in COM displacement due
      to heel rise was compared with the actual reduction in displacement. RESULTS: The
      estimated effect of heel rise on reduction in COM displacement was 23.4+/-7.6mm,
      whereas the actual reduction in COM displacement was 21.2+/-6.5mm (difference not
      significant, paired p = .185). CONCLUSION: During normal walking, heel rise from
      foot flat has a considerable role in raising the height of the COM when it is at
      its lowest, thus reducing its overall displacement. Insofar as reduction of COM
      vertical displacement may have important energy implications, appreciating the
      specific gait parameter of heel rise is key in rehabilitative approaches to
      improve gait disability.

PMID- 10943759
TI  - The contribution of vision to wheelie balance.
AB  - OBJECTIVE: To test the hypothesis that vision plays an important role in the
      maintenance of balance during a stationary wheelchair maneuver in which the
      wheelchair user lifts and maintains the chair's front wheels off the floor
      (wheelie). DESIGN: Within-subject comparisons of the ability of subjects to
      perform wheelies with their eyes open (EO) and their eyes closed (EC). SETTING:
      Kinesiologic laboratory. PARTICIPANTS: Ten able-bodied adults, a sample of
      convenience. MAIN OUTCOME MEASURES: Postural sway, as reflected by the standard
      deviation of sagittal-plane movements of the center of pressure of the chair's
      right rear wheel on a force platform during a 10-second stationary wheelie
      balance, and the number of mistrials. RESULTS: The postural sway for all trials
      (3 EO and EC data collections at the end of each of 3 one-hour training sessions)
      was 88% greater with the EC than with the EO condition (p < .001) and the number
      of mistrials was 324% greater (p = .001). By the end of the final training
      session, the postural sway with the EC (4.0cm) was still 100% greater than with
      the EO (2.0cm) (p < .001) although there was no longer a difference in the number
      of mistrials. CONCLUSION: Vision plays an important role in the maintenance of a
      stationary wheelie, but wheelies can be maintained with the eyes closed. These
      findings are relevant to the training of wheelchair users and also provide
      broader insights into the nature of wheelchair function and dynamic balance.

PMID- 10943760
TI  - Atypical gastrointestinal symptoms are not associated with gallstones in patients
      with spinal cord injury.
AB  - OBJECTIVE: To determine if nonspecific gastrointestinal (GI) symptoms justify
      cholecystectomy in patients with spinal cord injury (SCI). DESIGN: The frequency
      of GI symptoms was determined in a sample of patients with SCI in whom the
      presence or absence of gallstones had been previously determined by screening
      ultrasonography or a known history of cholecystectomy. The prevalence of various
      symptoms in patients with and without gallstones was compared. SETTING: The
      Spinal Cord Injury Unit of the Veterans Affairs Puget Sound Health Care System,
      which provides rehabilitation and longitudinal primary care for SCI veterans.
      PATIENTS: Two hundred ninety-four patients who had undergone either right upper
      quadrant ultrasonography or cholecystectomy in the past, and who completed a
      questionnaire concerning GI symptoms. MAIN OUTCOME MEASURE: Bivariate logistic
      regression was used to calculate odds ratios (ORs) to determine the strength of
      associations between the presence of each symptom and the presence of gallstones.
      RESULTS: Pain in the right upper quadrant or epigastrium that occurred after
      meals or at night was significantly associated with gallstones (OR: 3.5; 95%
      confidence interval [CI] 1.02-11.73). Abdominal pain in other locations and
      nonspecific symptoms such as bloating and nausea, were not predictive of the
      presence of gallstones. CONCLUSIONS: Nonspecific symptoms in patients with SCI
      are not associated with gallstones and do not justify cholecystectomy in patients
      with otherwise asymptomatic gallstones.

PMID- 10943761
TI  - Electrical stimulation: can it increase muscle strength and reverse osteopenia in
      spinal cord injured individuals?
AB  - OBJECTIVE: To study the extent to which atrophy of muscle and progressive
      weakening of the long bones after spinal cord injury (SCI) can be reversed by
      functional electrical stimulation (FES) and resistance training. DESIGN: A within
      subject, contralateral limb, and matching design. SETTING: Research laboratories
      in university settings. PARTICIPANTS: Fourteen patients with SCI (C5 to T5) and
      14 control subjects volunteered for this study. INTERVENTIONS: The left
      quadriceps were stimulated to contract against an isokinetic load (resisted)
      while the right quadriceps contracted against gravity (unresisted) for 1 hour a
      day, 5 days a week, for 24 weeks. MAIN OUTCOME MEASURES: Bone mineral density
      (BMD) of the distal femur, proximal tibia, and mid-tibia obtained by dual energy
      x-ray absorptiometry, and torque (strength). RESULTS: Initially, the BMD of SCI
      subjects was lower than that of controls. After training, the distal femur and
      proximal tibia had recovered nearly 30% of the bone lost, compared with the
      controls. There was no difference in the mid-tibia or between the sides at any
      level. There was a large strength gain, with the rate of increase being
      substantially greater on the resisted side. CONCLUSION: Osteopenia of the distal
      femur and proximal tibia and the loss of strength of the quadriceps can be partly
      reversed by regular FES-assisted training.

PMID- 10943762
TI  - Depression after spinal cord injury: relation to gender, ethnicity, aging, and
      socioeconomic indicators.
AB  - OBJECTIVE: To investigate the relation among aging, gender, ethnicity,
      socioeconomic indicators, and depressive symptoms after spinal cord injury (SCI).
      DESIGN: Survey was done to collect cross-sectional data. A mediational model was
      used to analyze the interrelationships between predictors and depressive outcome
      variables. SETTING: A large Southeastern rehabilitation hospital. PARTICIPANTS:
      Participants, identified from outpatient records who met the following inclusion
      criteria: (1) traumatic SCI; (2) at least 18 years old at the time of study; and
      (3) injured for at least 1 year. There was an initial pool of 1923 potential
      participants in 1997, of whom 1391 (72%) participated. MAIN OUTCOME MEASURES: The
      Older Adult Health and Mood Questionnaire, a 22-item measure of depressive
      symptoms designed following Diagnostic and Statistical Manual of Mental Disorders
      (DSM III-R) criteria, was used to measure depression. It has been validated
      against clinical assessments by psychiatrists and psychologists. RESULTS: Forty
      eight percent of the participants reported clinically significant symptoms.
      Minority participants, particularly women, were at a substantially higher risk
      for depressive symptoms. This risk diminished but did not disappear after
      controlling for years of education and income, both of which were highly
      negatively correlated with depressive symptoms. Aging factors were modestly
      positively correlated with depression, although education or income did not
      mediate these associations. CONCLUSIONS: Symptoms of depression are highly
      prevalent after SCI and are related to aging, gender or ethnicity, and
      socioeconomic status indicators (education and income).

PMID- 10943763
TI  - Wound measurement: the comparative reliability of direct versus photographic
      tracings analyzed by planimetry versus digitizing techniques.
AB  - OBJECTIVE: To investigate two methods of wound measurement (planimetry and
      digitizing) performed on two routinely used techniques of clinical wound
      assessment, tracings taken directly from a patient's wound (raw tracing) and from
      photographs of the wound (photographic tracing). DESIGN: We examined the level of
      repeatability and thus reliability of these methods, and determined if absolute
      measured wound size differed between the combinations of method and assessment
      procedures. PATIENTS: Seven patients (4 women, 3 men; mean age +/- standard error
      of the mean = 63.1+/-5.0yrs) with a total of 11 wounds. SETTING: Patients
      attended a podiatry outpatient department on two separate days for raw and
      photographic tracing of their wounds. For both of these trace types, a series of
      repeated recordings were conducted by a single investigator using planimetry and
      digitizing measurement methods. MAIN OUTCOME MEASURE: Independent statistical
      analyses (analysis of variance, p < .05) were conducted on logged coefficients of
      variation and logged means data to investigate for repeatability and for size
      differences, respectively. RESULTS: Planimetry produced a significantly larger
      degree of variability (thus less repeatability) than digitizing (p = .02) and
      also produced smaller readings (p = .00001). Averaging over methods also
      indicated that photographic tracings produced smaller readings than raw tracings
      (p = .019). CONCLUSION: For the wound sizes and shapes examined, tracings taken
      directly from the patients were found to be an inexpensive clinical and research
      assessment tool on which digitizing was conducted with a higher level of
      repeatability than planimetry. Further research is needed to determine if the
      current findings apply to a wider population within wound management clinics.

PMID- 10943764
TI  - Posterior femoral cutaneous nerve mononeuropathy: a case report.
AB  - Isolated posterior femoral cutaneous nerve (PFCN) lesions are rare, with only six
      cases reported in the modern literature and one case documented with a nerve
      conduction study. A 25-year-old woman had sensory loss in the posterolateral
      thigh after two right gluteal intramuscular injections. Nerve conduction studies
      using Dumitru's technique showed a 9microV response on the asymptomatic side, but
      no response on the symptomatic side, and no abnormalities on needle examination
      of the back and lower extremities. Although a single case does not prove the
      validity of a technique, this case provides the rare opportunity to demonstrate
      the utility of Dumitru's technique.

PMID- 10943765
TI  - Nonsurgical treatment for radicular of pain of zygoapophyseal joint cyst origin:
      therapeutic selective nerve root block.
AB  - We report the first case of zygoapophyseal joint cyst-induced radicular pain
      successfully treated with therapeutic selective nerve root block. A 56-year-old
      dentist presented with pain involving the lateral thigh, lateral calf, and foot
      dorsum that worsened with standing and walking. Magnetic resonance imaging of the
      lumbar spine showed a cyst emanating from the right L4-L5 zygoapophyseal joint,
      resulting in central canal and lateral recess stenosis. The patient was treated
      with two fluorscopically guided therapeutic L5 selective nerve root blocks. The
      patient remained pain free at 18-month follow-up.

PMID- 10943766
TI  - Inclusion body myositis masquerading as polymyositis: a case study.
AB  - A case of inclusion body myositis masquerading as unresponsive polymyositis is
      presented. A 56-year-old woman diagnosed with "biopsy-proven" polymyositis in
      1991 was referred to our clinic in 1997 with progressive, painless weakness that
      was unresponsive to steroid therapy. Further evaluation, including
      electromyography and review of the original muscle biopsy specimen, found a
      diagnosis of inclusion body myositis, leading to a change in the patient's
      prognosis and management. Inclusion body myositis is frequently mistaken for
      polymyositis, despite the fact that it is now the most common inflammatory
      myopathy affecting people older than 50 years. The purpose of this report is to
      increase awareness of this disease, to enhance early diagnosis, and to ensure
      appropriate management. We discuss the clinical findings, pathogenesis, and
      physiatric management, as well as compare this disease with other idiopathic
      inflammatory myopathies.

PMID- 10943767
TI  - Ulnar neuropathy resulting from diffuse intramuscular hemorrhage: a case report.
AB  - The ulnar nerve can be injured in the arm, forearm, and wrist. This report
      describes a 79-year-old woman who presented to the emergency department with
      acute lower extremity weakness and vertigo. Her medical history was significant
      for moderate to severe aortic stenosis, hypertension, and a remote intravascular
      thrombosis in the right forearm. The patient was diagnosed with a transient
      ischemic attack and was treated with anticoagulants. Three days after beginning
      anticoagulation therapy, she developed a diffuse intramuscular hemorrhage in the
      arm, which compromised predominantly ulnar fibers. The clinical, radiologic, and
      electrodiagnostic abnormalities are reviewed, and the possible etiologies of
      ulnar neuropathy are discussed. To our knowledge, this is the first report of
      ulnar neuropathy secondary to diffuse hemorrhage into the muscles of the arm.

PMID- 10943768
TI  - Electrodiagnosis in the upper limb.

PMID- 10943769
TI  - Lead poisoning and its elimination: an opportunity for success.

PMID- 10943770
TI  - Associate and baccalaureate degree final semester students' perceptions of self
      efficacy concerning community health nursing competencies.
AB  - A quantitative study was undertaken to examine whether final semester associate
      degree nursing (ADN) and baccalaureate degree nursing (BSN) students who
      experienced community health nursing content perceived themselves as self
      efficacious to work as community health nurses (CHNs) with individuals, families,
      and communities. Additionally, the study examined the variance of perceived self
      efficacy (PSE) accounted for by antecedent variables, performance accomplishments
      (PA), vicarious experience (VE), verbal persuasion (VP), and emotional arousal
      (EA). Questionnaires were mailed to faculty liaisons from 34 randomly selected
      National League for Nursing (NLN)-accredited schools in the United States.
      Statistical analysis revealed that the ADN and BSN final semester students
      perceived themselves to be equally self-efficacious to work with individuals and
      families. Significant differences were found, however, between the ADN and BSN
      students on PSE to work with communities. PA and VE explained 15% of the PSE
      variance suggesting that actual and VE contributes positively to a students' PSE
      to work as a CHN.

PMID- 10943771
TI  - A student-directed community project to support sexually abused women veterans
      suffering from post-traumatic stress disorder.
AB  - While awareness of post-traumatic stress disorder (PTSD) and sexual abuse
      continues to grow, it has only been during the past few years that the military
      has realized the prevalence and impact of sexual abuse inflicted upon women while
      on active military duty. Though Veteran Administration (VA) agencies throughout
      the United States have given concerted attention to this problem, published
      resources specific to PTSD and military sexual abuse have been limited. In this
      article the authors present the results of a 2(1/2)-year endeavor to address the
      problem of PTSD and military sexual abuse at the Tulsa VA Outpatient Clinic. The
      project started with a research study and the subsequent initiation of a PTSD
      women veterans support group, and culminated in the development of resource
      manuals for both professional staff and women veterans.

PMID- 10943772
TI  - Feria de Salud: implementation and evaluation of a communitywide health fair.
AB  - Evaluating the effectiveness of community interventions is a major responsibility
      for community health nurses (CHNs). Without evidence of the effectiveness of
      interventions, their impact on the health status of populations or communities
      cannot be determined. This article presents the planning, implementation, and
      evaluation processes of a communitywide health fair. This fair was held in a
      suburban community of approximately 12,000 individuals, located 20 kilometers
      outside of Mexico City. The health fair was one component of a collaborative
      project aimed at addressing the overall health needs of the community. Emphasis
      is on the development and utilization of measurable objectives in evaluating both
      processes and outcomes of the health fair. Green and Kreuter's (1991) PRECEDE
      PROCEED program planning model provided direction for program planning and
      evaluation. The findings of process, impact, and outcome evaluation are
      described, providing both qualitative and quantitative measures of program
      effectiveness. These findings provide direction for program replication and
      modification. Recommendations address the utility of theory-based assessment,
      program planning, and evaluation, the importance of formative evaluation, and the
      need for cultural sensitivity in community health program planning.

PMID- 10943773
TI  - Promoting elder wellness through a community-based blood pressure clinic.
AB  - As the American population ages, we can expect to find greater numbers of older
      adults with chronic diseases and health concerns. Therefore the implementation of
      communitybased blood pressure clinics that promote elder wellness becomes
      increasingly important. This article will describe the development,
      implementation, and evaluation of a community-focused elder wellness program in a
      rural community using Anderson and McFarlane's (1996) Community-as-Partner model
      as a theoretical framework for community health nursing practice. Evaluation
      results of the elder wellness program suggest that blood pressure screenings
      provide community health nurses (CHNs) with unique opportunities to promote
      wellness in older adults when provided in an atmosphere that encourages nurse
      client interactions.

PMID- 10943774
TI  - Community development through faculty practice in a rural nurse-managed clinic.
AB  - This article describes a community-academic partnership that led to the
      development of a nurse-managed clinic (NMC) in 1996 in a rural Indiana area
      designated by the state as a medically underserved area (MUA) and a health
      professional shortage area (HPSA). Application of the community development model
      in faculty practice is described in relation to the clinic. The project is
      ongoing; lessons learned to date, which have implications for others involved in
      faculty practice, are described.

PMID- 10943775
TI  - Caregiving and help seeking by mothers of low birthweight infants and mothers of
      normal birthweight infants.
AB  - The purpose of this research was to describe perceptions of infant health,
      caregiving at home, and help seeking by mothers of low birthweight (LBW) infants
      (n = 30) and mothers of normal birthweight infants (n = 30). In this descriptive
      study, data were analyzed through multiple regression, t tests, and content
      analysis of responses to researcher-constructed questionnaires. There were
      statistically significant relationships between: infant health and both
      confidence in caregiving (R2 = 0.18, p<0.001) and caregiver burden (R2 = 0.29,
      p<0.001); preparation for caregiving and confidence in caregiving (R2 = 0.10,
      p<0.05); and confidence in caregiving and caregiver burden (R2 = 0.12, p<0.01).
      Compared with mothers of normal birthweight infants, mothers of LBW infants
      perceived poorer infant health, t (58) = -2.02, p = <0.05, and more caregiver
      burden, t (58) = 3.50, p = <0.001. Mothers reported seeking help from a variety
      of resources, mostly nonprofessional for questions on infant care or nonserious
      infant health problems, and mostly physicians for questions on serious infant
      health problems. Nurses can use knowledge of mothers' perceptions of infant
      health, caregiving, and help seeking to facilitate mothers' management of
      caregiving and resource use.

PMID- 10943777
TI  - Street music or the blues? The lived experience and social environment of
      depression.
AB  - Life's complexity is a haunting melody of continuously interacting variables ....
      Professional practice in nursing seeks to promote symphonic interaction between
      man [sic] and environment. . . (Rogers, 1970, pp. 41, 122). The purpose of this
      phenomenological study was to explore the lived experience of clinical depression
      for women in the context of their social relations and environment. Twelve
      ethnically diverse female friend dyads were interviewed and completed the Beck
      Depression Inventory (BDI). Seventeen of these women had experienced a major
      depression in the past or were in treatment for clinical depression at the time
      of the study. This depression was characterized by dissonance experienced in
      childhood abuse and incest, uncontrollable moods despite self-medication, abusive
      or negligent therapy, failed social relationships in adulthood, and a lack of
      resources in the environment. In contrast, seven healthy women described their
      social environment as generally resonant and connected. Prevention of childhood
      abuse and racism, relief from economic hardships, early diagnosis, and safe,
      effective treatment are essential in helping women to survive clinical
      depression. Nurses in the community are in a unique position to affect this
      public health problem.

PMID- 10943776
TI  - Social support and psychological functioning among high-risk mothers: the impact
      of the Baby Love Maternal Outreach Worker Program.
AB  - This study compared two groups of high-risk Medicaid-eligible mothers, 221 who
      participated in a maternal home visitation program and 198 who did not, to
      determine whether program participation was associated with improvements in the
      mothers' psychological functioning 1 year after delivery, and whether these
      improvements were associated with the type and intensity of support provided by
      home visitors. The results suggest that, compared to nonparticipants,
      participants provided with more intensive home visitor support had significantly
      higher self-esteem (p = 0.039) and were less depressed (p = 0.015). Participants
      with less intensive home visitor support, however, did not differ significantly
      from nonparticipants in their self-esteem or depression levels. No significant
      differences were observed in the perceived stress levels of participants as
      compared with nonparticipants, regardless of the intensity of home visitor
      support. Mothers who had support from the baby's father, however, had
      significantly lower perceived stress levels than mothers with no support from the
      baby's father (p = 0.046). Moreover, the type of support provided by home
      visitors (emotional, instrumental, informational) did not appear to be related to
      the mothers' psychological functioning. This study suggests that the intensity of
      support is an important component of maternal home visitation programs that aim
      to improve women's psychological functioning.

PMID- 10943778
TI  - The challenge of choosing a pediculicide.
AB  - Head lice is the most frequently occurring communicable disease, except for the
      common cold, among children in the United States. The impact on a family facing
      the challenge of head lice is tremendous, ranging from emotional to financial
      distress. Challenges also face the health care provider and school personnel.
      Many over-the-counter preparations and prescription products are available to
      combat head lice. With the alleged advent of pediculicide-resistant head lice,
      many other products and applications not necessarily intended to treat head lice
      are being recommended. The purpose of this article is to outline the products and
      procedures currently being utilized and to provide a starting point for treating
      head lice.

PMID- 10943779
TI  - Evaluation of telenursing outcomes: satisfaction, self-care practices, and cost
      savings.
AB  - Info-Sante CLSC, the Quebec telenursing service, is a telephone health line
      nursing service that was implemented in 1995 in every local community service
      center (CLSC; n = 141) of 15 regional health authorities in the Province of
      Quebec, Canada. It is, at present, one of the most important first-line health
      services and it operates in continuity with the other resources in the health and
      social service system. Info-Sante CLSC operates 24 hours a day, 7 days a week,
      and received more than 2,260,000 calls in 1997. This article will report the
      findings from the first province-wide survey of the service, based on a
      stratified random sample of 4,696 callers. The findings revealed that most
      respondents were highly satisfied with the service; they followed the nurses'
      advice and carried out self-care measures as recommended. Nursing interventions
      helped respondents feel self-reliant, like they could solve the same or similar
      problems should they occur in the future. The vast majority of respondents
      considered that the call they made to Info-Sante CLSC was useful in finding a
      solution to their problems. The vast majority also claimed that they would
      certainly call Info-Sante CLSC again should another problem occur. The majority
      reported they would have turned to another type of resource if Info-Sante CLSC
      had not existed; half of the respondents stated that they would have used
      emergency departments and a third would have consulted a doctor in private
      practice.

PMID- 10943780
TI  - The value of intraoperative intravascular ultrasound for determining stent graft
      size (excluding abdominal aortic aneurysm) with a modular system.
AB  - Since the introduction of endovascular stent grafts at our institution we have
      used intraoperative intravascular ultrasound (IVUS) to definitively determine
      stent graft size. In this study, expected stent graft size, based on preoperative
      helical CT scan measurements, was compared with the actual final size, based on
      intraoperative IVUS measurements. Between December 1996 and January 1998, 54
      patients were treated with an AneuRxTM bifurcated stent graft. Preoperatively all
      patients underwent angiography and helical CT scanning. Expected stent graft size
      was determined according to these measurements. The final stent graft size was
      based on IVUS measurements acquired during the procedure. Differences in expected
      and final size were compared and follow-up endoleaks were also noted. Differences
      in diameter measurements between CT and IVUS were compared using the paired
      Student's t-test. Differences in expected and chosen stent graft length were
      compared using the McNemar's test for paired proportions of binomial outcomes.
      Our results showed that helical CT scanning overestimates diameter and
      underestimates length. This underestimation of length is explained by the
      tortuosity of the aorta and iliac arteries while using axial slices of the CT
      scan. The last-minute corrections based on the intraoperative IVUS measurements
      did not result in a high incidence of endoleaks at fixation zones. In our
      opinion, the possibility of making final corrections in the choice of diameter or
      length of the stent graft is the additional value of intraoperative IVUS.

PMID- 10943781
TI  - Predictive factors for early success of endovascular abdominal aortic aneurysm
      repair.
AB  - To identify predictive factors for postoperative success and potential predictors
      for satisfactory outcome of endovascular grafting for abdominal aortic aneurysm
      (AAA), we collected data from our prospective database, which includes a series
      of consecutive patients undergoing endovascular repair at the Vascular Surgery
      Unit, Policlinico Monteluce, Perugia, Italy. From April 1997 to July 1998, 202
      patients were referred to our Unit for elective AAA repair; 94 patients (47%)
      were selected for endografting. Placement of the graft using endovascular
      technique without conversion to open laparotomy, in addition to no mortality,
      major morbidity, or endoleak at 30-day follow-up, was defined as postoperative
      success. The influence of anatomical features on postoperative results was
      analyzed by univariate and multivariate analysis. Our experience shows that
      endoluminal repair of AAA is safe and effective in the short term and male
      patients with small aneurysms are optimal candidates for successful repair.

PMID- 10943782
TI  - The role of polyester patch angioplasty in carotid endarterectomy: a multicenter
      study.
AB  - The objectives of this study were to examine the morphology, restenosis,
      dilatation, and possible complications of polyester collagen impregnated carotid
      patches. Between March 1994 and January 1995, 207 patients (56 females and 151
      males) undergoing 221 carotid endarterectomies (CE) with a collagen-impregnated
      knitted polyester patch were enrolled in a European prospective multicenter
      study. Patches were used for arteries deemed to be smaller than usual by visual
      inspection. General anesthesia was used in 201 procedures (91%), and a shunt was
      used in 76 procedures (34.4%). One hundred fourteen CE (51.6%) were checked by a
      perioperative arteriography or angioscopy. The diameter of the internal carotid
      artery (ICA) and carotid bulb (CB) were measured by duplex scan both
      preoperatively and every 6 months during follow-up. The main end point was
      carotid occlusion or restenosis, defined as a stenosis of 50% or more according
      to NASCET criteria. Carotid polyester-impregnated patches appear to be reliable.
      The patch was easy to cut and suture, and hemostasis was obtained immediately. No
      rupture occurred. However, the higher restenosis rate in women may restrict the
      use of polyester patch to men.

PMID- 10943783
TI  - Influence of coronary artery and contralateral carotid artery status on long-term
      results of carotid artery surgery.
AB  - The main cause of death and long-term disability of patients undergoing carotid
      artery surgery is coronary artery disease. To identify the prognostic value of
      the status of the contralateral artery, we studied the course of 224 consecutive
      patients in whom one or both carotid arteries were operated on at our institution
      between 1985 and 1995. The 224 patients were divided into three groups: group I
      (n = 56) had an occluded contralateral carotid artery, in group II (n = 56) both
      carotids were operated on, and group III (n = 112) had a normal contralateral
      carotid artery. The clinical status of all patients except one was ascertained by
      one of us. We found that the status of the contralateral artery does not
      influence the long-term prognosis of patients undergoing carotid artery surgery.
      A periodic cardiological and vascular follow-up of these patients seems warranted
      to improve their survival.

PMID- 10943784
TI  - Is there differential access to carotid endarterectomy based on gender?
AB  - The purpose of this study was to determine whether there was differential access
      to carotid endarterectomy (CEA) based on gender at our institution. In 1995, the
      year after ACAS results were published, 1774 carotid duplex studies were
      performed in our vascular laboratory in 765 men and 1009 women. The incidence of
      50-99% carotid stenosis was 13% (n = 235) overall and did not differ between men
      (13.3%; 102/765) and women (13.2%; 133/1009). The frequency that patients
      subsequently underwent CEA was determined to assess whether men with significant
      carotid stenosis were more likely to undergo CEA than women. Attempts were made
      to contact patients with 50-99% stenosis directly. Data were available for 101
      patients (41 men, 60 women) with 50-99% carotid stenosis diagnosed by carotid
      duplex. There was conflicting information regarding the possibility of gender
      bias in the selection of candidates for CEA: logistic regression analysis
      suggested that disease severity dictated surgical intervention, however, a
      significantly lower percentage of women with ICA/CCA peak systolic ratios > or
      =2.9 underwent CEA. This study cannot refute the possibility that gender bias
      existed in the selection of patients for CEA.

PMID- 10943785
TI  - The underestimated advantages of iliofemoral endarterectomy.
AB  - Iliofemoral endarterectomy was invented 50 years ago, but it is seldom practiced
      today for two reasons. The first is that it is technically challenging and the
      second is that outcome in early series was poor. Our preliminary experience
      having been more encouraging, we have continued to perform iliofemoral
      endarterectomy for the past 20 years. The purpose of this retrospective study was
      to evaluate our results and compare them with results of alternative techniques
      described in recent literature. We have performed a total of 176 iliofemoral
      endarterectomies in patients with normal or nearly normal aortas. The procedure
      involved the entire network including the common iliac artery, external iliac
      artery, and common femoral artery in 108 cases (group I), the common iliac artery
      with or without the external iliac artery in 40 cases (group II), and the
      external iliac arteries and the common femoral artery with or without the deep
      femoral artery in 28 cases (group III). From our results we conclude that
      iliofemoral endarterectomy should be used as a first-choice modality in patients
      with normal or nearly normal aortas who present with iliac lesions that are
      either too long for balloon angioplasty or impossible to recanalize. It
      eliminates the risk of graft infection and false aneurysm. Restenosis can be
      treated by balloon angioplasty. It also saves the cost of a prosthesis.

PMID- 10943786
TI  - Predictors of outcome when reoperating for early infrainguinal bypass occlusion.
AB  - The purpose of this study is to identify factors that predict outcome after
      intervention for early (<30 days) infrainguinal graft thrombosis. We reviewed the
      medical records, arteriograms, and follow-up studies of patients who underwent
      infrainguinal bypass for limb salvage between 8/91 and 9/98 and whose graft
      failed <30 days from the index procedure. Five factors were analyzed: (1)
      conduit: single segment saphenous vein versus alternative vein or composite
      conduit (20 vs. 13 patients); (2) repair modality: construction of a new graft at
      the time of the initial take-back procedure versus local revision and/or
      thrombectomy alone (12 vs. 21 patients); (3) run-off: good run-off versus poor
      run-off (20 vs. 13 patients); (4) operative findings: the presence of a
      correctable problem versus noncorrectable problem (20 vs. 13 patients); and (5)
      surgical history: previous versus no previous ipsilateral bypass (16 vs. 17
      patients). These variables are statistically significant risk factors that can be
      used in combination to predict outcome. Unless a focal lesion clearly responsible
      for graft occlusion is found, complete graft replacement should be considered
      even if the new bypass must be prosthetic. The costs and morbidity of repeated
      procedures argue for primary amputation when adverse risk factors exist.

PMID- 10943787
TI  - Endogenous fibrinolysis in patients with lower extremity ischemia.
AB  - To explore the relationship between disorders of endogenous fibrinolysis and
      thrombosis in patients with lower extremity ischemia, we measured the activity of
      tissue plasminogen activator (tPAac) and plasminogen activator inhibitor (PAlac)
      and the antigens of tissue plasminogen activator (tPAa) and inhibitor (PAla) in
      plasma from 420 patients treated for lower extremity ischemia. Values and ratios
      observed were compared with those in healthy volunteers. Additionally, values and
      ratios in the patients were examined with respect to the severity of ischemia and
      site of atherosclerotic occlusion or stenosis (pelvic compared with
      femoropopliteal or crural). Patients with lower extremity ischemia had higher
      plasma concentrations of PAla (p<0.01) and PAlac (p<0.0001) than healthy
      volunteers. In patients with rest pain or gangrene, the ratio of tPAac to PAlac
      was higher than in patients with claudication (p<0.05). The elevation of tPAac in
      patients with the more severe form of lower extremity ischemia is probably the
      feedback protective reaction on prothrombotic mechanisms of the organism suffered
      from severe atherosclerosis. Results did not vary according to the site of
      occlusion or stenosis. Our study found defects in endogenous fibrinolysis in
      patients with lower extremity ischemia. A defect in fibrinolysis may contribute
      to the development of thrombosis in native arteries and bypasses.

PMID- 10943788
TI  - Preoperative intraarterial thrombolysis before surgical revascularization for
      popliteal artery aneurysm with acute ischemia.
AB  - Because a popliteal artery aneurysm (PAA) generates emboli that progressively
      deteriorate the distal arterial network, they can constitute limb-threatening
      lesions. In 20 to 40% of cases, discovery of PAA coincides with sudden occlusion
      and resulting acute ischemia. In 40 to 60% of these patients, surgical
      revascularization fails and amputation is required. The objective of this
      prospective study was to assess the value of intraarterial thrombolysis to
      restore distal runoff before surgical revascularization. Between January 1, 1992
      and December 31, 1996, we treated 15 PAA causing acute ischemia in 15 male
      patients with a mean age of 66.7 years (range, 44 to 87 years). Diagnosis was
      documented by clinical examination and ultrasound imaging. Intraarterial
      thrombolysis was performed under arteriographic control through a multiperforated
      catheter inserted by the anterograde femoral route to the thrombus. After an
      initial bolus of 100,000 U of urokinase, 600,000 to 1,600,000 U was continuously
      infused over a period of 6 to 18 hr. Heparin sodium was administered throughout
      thrombolysis. Surgical revascularization was performed within 1 to 4 days (mean,
      2 days) after thrombolysis by exclusion and bypass in 14 cases and percutaneous
      transluminal angioplasty with stenting in 1 case. The ensuing results showed
      that, if performed carefully, intraarterial thrombolysis can safely prepare
      patients presenting with occluded PAA with acute ischemia for surgical
      revascularization to restore distal runoff. We use this combined technique
      routinely in our department. Morbidity is low in comparison with the risks of
      amputation.

PMID- 10943789
TI  - Selective botulinum chemodenervation of the scalene muscles for treatment of
      neurogenic thoracic outlet syndrome.
AB  - Patients with thoracic outlet syndrome (TOS) who improve temporarily after
      anesthetic blockade of the anterior scalene muscles have been shown to improve
      after ultimate surgical decompressions at the interscalene triangle. Anesthetic
      blockade of the scalene muscles, even with the addition of steroids, however,
      rarely produces any prolonged relief as patients are awaiting definitive surgery.
      The present study was undertaken to determine if more effective and prolonged
      relief might be obtained with electrophysiologically and fluoroscopically guided
      selective injection of the scalene muscles with botulinum toxin, which has been
      used in the past for treating conditions associated with spasm of cervical
      muscles. In 14 of 22 patients (64%) with a clinical diagnosis of TOS, there was
      more than a 50% reduction of symptoms measured by a 101-point scale for at least
      1 month after botulinum chemodenervation of the scalene muscles. Only 4 of the 22
      patients (18%) had a 50% reduction of symptoms for at least 1 month after
      injection with lidocaine and steroids. In no patient were the results of
      lidocaine and steroid injection superior to botulinum chemodenervation.
      Chemodenervation had a mean duration of effect of 88 days. No significant side
      effects were encountered with botulinum chemodenervation except for mild
      transient dysphagia in two cases. These results appear to demonstrate that
      botulinum chemodenervation of the scalene muscles may be helpful in alleviating
      symptoms in patients with TOS awaiting definitive surgical decompression.

PMID- 10943791
TI  - Ambulatory conservative hemodynamic management of varicose veins: critical
      analysis of results at 3 years.
AB  - This report describes the results of our 3-year experience using ambulatory
      conservative hemodynamic management (ACHM) for lower extremity venous
      insufficiency involving the greater saphenous vein (GSV), with specific analysis
      of recurrence due to neoformation of vessels. We performed 289 ACHM procedures in
      259 consecutive patients with GSV-related varicose veins. Follow-up clinical
      examination and Doppler ultrasound imaging was carried out at 3, 6, 12, 24, and
      36 months in all cases to assess formation of neovessels supplied either by the
      superficial (A) or deep (B) venous system. Our data showed that ACHM achieved
      excellent improvement, with complete disappearance of varicose veins in 41.2% of
      cases, good improvement in 43%, fair improvement in 14.1%, and no improvement in
      1.7%. The only predictor of outcome was the quality of drainage from the GSV
      vein. Poor drainage leads to neoformation of vessels supplied by the superficial
      (A) venous system. In about 50% of cases, drainage appeared spontaneously within
      1 year, with a subsequent reduction in formation of neovessels. Neoformation of
      vessels supplied by the deep (B) venous system (10%) was independent of the
      quality drainage. This finding suggests that formation of these neovesseis is
      unrelated to the surgical method used to treat varicose veins. In patients with
      poor drainage of the saphenous network, neoformation of vessels supplied by the
      superficial (A) venous system is predictable with regard to both topography and
      delay. ACHM is a good tool for treatment of varicose veins, as reliable
      statistical prediction of mid-term results is possible using available models.

PMID- 10943790
TI  - Binding kinetics of triclosan (Irgasan) to alloplastic vascular grafts: an in
      vitro study.
AB  - The aim of this study was to investigate the binding kinetics of triclosan
      (Irgasan) to alloplastic vascular grafts and to examine its antimicrobial
      activity against various microbial pathogens in vitro. Vascular grafts made by
      Intergard (Intervascular), Fluoropassiv (Vascutek), and Gore-tex (Gore) were
      examined. Grafts were incubated in 10 g/L triclosan (Irgasan), dried, sterilized,
      and incubated in RPMI medium. One-centimeter segments of the grafts were resected
      under sterile conditions at intervals of minutes, then hours, followed by days
      and up to 4 weeks. Samples were stored frozen at -20 degrees C for the
      measurement of triclosan bound to the vascular graft by high-performance liquid
      chromatography (HPLC). The binding kinetics under perfusion conditions were
      determined for Intergard grafts, which were perfused with 50 mL of nutrient
      medium for 24 hr. Samples were taken at various time intervals for the
      measurement of triclosan. The antimicrobial activity of triclosan against
      Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans as well as
      Enterococcus faecium was determined. Triclosan effectively binds to vascular
      graft without the use of intermediate binding substances. It stayed on the graft
      for the duration of 4 weeks. Under both static and perfusion conditions, the
      binding kinetics are similar. Triclosan binds most effectively to Intergard
      grafts, less so to Fluoropassiv grafts, and not at all to Gore-tex material.
      Antimicrobial activity of triclosan is very effective against S. aureus and E.
      faecium but not against P. aeruginosa.

PMID- 10943792
TI  - Effect of p53 gene therapy combined with CTLA4Ig selective immunosuppression on
      prolonged neointima formation reduction in a rat model.
AB  - In a previous study, we have demonstrated a significant reduction of neointimal
      formation following adenovirus-mediated gene transfer of p53 to the injured rat
      carotid artery. The purpose of this study was to determine if the effect of p53
      gene in reducing neointimal formation would still be present up to 8 weeks after
      arterial injury and whether it could be enhanced by adding immunosuppression.
      Cytotoxic T lymphocyte-associated antigen-4 Ig (CTLA41g), a novel
      immunosuppressive agent, is a recombinant soluble protein that blocks T cell
      dependent immune response. Animals were divided into eight groups (n = 6 in
      each). In vivo gene transfer was used in isolated segments of balloon-injured rat
      carotid arteries. Genetically modified adenovirus encoding for wild-type p53
      protein was applied at 8 x 10(10) pfu/mL. Control rats received adenovirus null
      at the same concentration. A daily dose of 300 microg of CTLA41g was given
      intraperitoneally, either once, twice, or three times. Expression of p53 was
      determined by Western blot analysis. Neointimal formation was assessed at 4 or 8
      weeks by harvesting carotid arteries and determining the intima/media (I/M) ratio
      cross-sectional area measurements. p53 expression was confirmed by Western blot
      analysis. We concluded that adenovirus-mediated p53 gene transfer significantly
      decreases the formation of neointima up to 8 weeks following rat carotid injury.
      However, there is loss of effectiveness on neointimal formation inhibition as
      time elapses. When CTLA41g is added, there is significant improvement in results,
      with sustained neointimal formation inhibition at 8 weeks after the procedure.

PMID- 10943793
TI  - Anomalies of inferior vena cava and left renal vein: risks in aortic surgery.
AB  - Although most aortic surgery is now routinely performed without incident, major
      venous anomalies can cause unexpected bleeding. In the last 6 years, 4 of 166
      patients undergoing abdominal aortic surgery at our institution were found to
      have a major venous anomaly, including a double inferior vena cava (2), a
      preaortic iliac vein confluence (1), and a circumaortic renal collar (1). The 3
      men and 1 woman had a mean age of 62.3 years (range, 56 to 68 years). All four
      patients underwent surgery for an abdominal aortic aneurysm. Preoperative imaging
      revealed all of the venous anomalies except for the renal collar. Unexpected
      venous injuries complicated the operation in one patient who had a double
      inferior vena cava and an inflammatory abdominal aortic aneurysm and in the
      patient with the circumaortic renal collar. Major venous anomalies are rarely
      encountered in patients undergoing aortic surgery. Preoperative assessment and
      intraoperative awareness are important to prevent unexpected venous injuries.
      Patients with an anomaly of the left renal vein and an inflammatory abdominal
      aortic aneurysm are at a particularly high risk.

PMID- 10943794
TI  - Recurrent varicose veins of both lower limbs due to bilateral ovarian vein
      incompetence.
AB  - A case of a 43-year-old female patient with mild pelvic pain and bilateral
      recurrent varicose veins due to incompetence of both ovarian veins is presented
      here. Ovarian vein incompetence was suspected from the presence of vulva
      varicosities and was confirmed by transvaginal ultrasound and descending ovarian
      venography. Treatment with transcatheter embolization of the ovarian veins was
      followed by local excision of the leg varices. Four years later, the patient
      remains asymptomatic and without any recurrence of varicose veins in both lower
      limbs.

PMID- 10943795
TI  - Infrarenal aortic rupture in association with a contiguous polymicrobial
      intraabdominal abscess including Eikenella corrodens.
AB  - Aortic rupture in association with a contiguous intraabdominal abscess is rare.
      We report an unusual case of aortic rupture in association with a polymicrobial
      abscess and review the related literature. Cultures grew Eikenella corrodens, a
      rare intraabdominal pathogen, as well as betahemolytic streptococcus and S.
      viridans. The patient was successfully managed by aortic ligation followed by an
      extraanatomic bypass.

PMID- 10943796
TI  - Internal carotid artery pseudoaneurysm related to pregnancy.
AB  - Arterial rupture is a common cause of maternal death. The increased tendency of
      true and false aneurysms to develop or rupture with advancing gestational age
      suggests that hemodynamic, hormonal, or other physiologic changes of pregnancy
      may play a role in their formation. To our knowledge, pseudoaneurysm formation
      from a carotid dissection or a ruptured true aneurysm related to pregnancy has
      not been previously reported. We report the successful repair of a large
      extracranial internal carotid artery pseudoaneurysm related to pregnancy. The
      clinical presentation, diagnostic modalities, surgical exposure, and treatment
      options for high internal carotid artery aneurysms will be discussed.

PMID- 10943797
TI  - Considerations in the management of aneurysms of the superior mesenteric artery.
AB  - Aneurysms of the superior mesenteric artery (SMA) are rare, accounting for 5.5%
      of all splanchnic aneurysms and <0.5% of all intraabdominal aneurysms. Previous
      reports have characterized these aneurysms among splanchnic artery aneurysms.
      However, these aneurysms are quite different in terms of etiology, presentation,
      and treatment, and their independent consideration is warranted. We report a
      patient with a traumatic SMA aneurysms who was successfully treated with surgical
      resection and distal revascularization. We also present an alternative technique
      of retrograde aorto-SMA bypass using autologous vein that prevents kinking. Also
      included is a review of the recent literature as it pertains specifically to SMA
      aneurysms.

PMID- 10943798
TI  - Current developments in thoracoscopic sympathectomy.

PMID- 10943799
TI  - Substance abuse and parenthood: biological mechanisms--bioethical challenges.
AB  - This review catalogues the long-term health effects of parental recreational drug
      abuse on the fetus and the subsequent well-being of the child. It is hard to
      conceive that parents would knowingly harm the health of their children, yet
      toxic effects resulting from ignorance, addiction or any of a number of
      socioeconomic factors are still responsible for handicapping countless
      potentially healthy offspring. The negative effects of female recreational drug
      and alcohol abuse during pregnancy are well documented, but exposure prior to
      conception and male-mediated effects are less well publicized. Abnormalities in
      the sperm are prevalent among men who consume recreational drugs, and birth
      defects are more often linked with paternal than with maternal DNA damage. This
      review is divided into three parts. Part I describes the biology and potential
      mechanisms of adverse alterations in reproductive potential, Part II explores the
      socioeconomic determinants of substance use, and raises the question of poverty.
      Drug-induced disability is not evenly distributed among the population as there
      are ethnic and socioeconomic disparities of infant mortality, childhood morbidity
      and reproductive dysfunction. Part III describes the author's conclusion that
      fundamental social change is needed to protect future children without
      threatening parents' basic freedom, and real change requires new beliefs and
      prioritics that must evolve from the ground up. An ecological model of care
      concentrating on health issues is described. Such an ecological model of care is
      in tune with the fundamental principles of bioscience ethics and emphasises that
      high quality education, health and good preconceptional/prenatal care are
      essentials in the search for greater equity in standard of living across a
      population.

PMID- 10943800
TI  - Ethics, society and occupational reproductive hazards: fetal consequences?
AB  - Occupational exposures to agents such as lead can adversely affect fetal outcome.
      With the US Supreme Court decision in the Johnson Controls case regarding the
      legality of employer's fetal protection policies, increasing responsibility lies
      with women to make decisions regarding exposure to potentially hazardous agents
      in the workplace. What are some of the ethical issues that society needs to
      address with respect to this responsibility? This paper considers the ethical
      principles of respect for autonomy, nonmaleficence, beneficence, justice, and
      self interest from the perspectives of the potential mother and those concerned
      with protecting the fetus. Since the fetus cannot make decisions, the potential
      role of society in protecting fetal rights in the context of workplace exposures
      is explored.

PMID- 10943802
TI  - Gender differences in gynecologist communication.
AB  - The intimate nature of gynecological health problems requires the physician's
      specific attention. On the basis of previous findings in primary care, female
      gynecologists are expected to communicate more affectively than men. This study
      addressed gender differences in gynecologist communication behavior by comparing
      videotapes of real-life outpatient encounters with female (N = 107) and male (N =
      196) gynecologists by means of bivariate and multilevel analysis. Only a few
      gender differences were found: female gynecologists performed longer physical
      examinations, showed more global attentiveness, and asked fewer medical
      questions. Either the duration of the medical education or the type of
      statistical analysis may account for this lack of gender differences.

PMID- 10943801
TI  - Should genetic health care providers attempt to influence reproductive outcome
      using directive counseling techniques? A public health prospective.
AB  - Many areas of agreement exist among genetic health care (GHC) professionals
      (i.e., MD and PhD clinical geneticists, master's level genetic counselors, and
      others) and public health (PH) professionals. However, there are in our opinion
      at least two areas or tenets where a distinct difference of opinion exists. Two
      tenets widely expressed by prenatal GHC professionals are: (1) they should never
      attempt to influence the outcome of a pregnancy, and (2) they should only use non
      directive genetic counseling techniques. From a PH perspective, these tenets
      could be viewed in some instances as counterproductive and contrary to a major
      goal of PH (i.e., to improve the health and well-being of all residents,
      including newborns). For example, PH's message regarding fetal alcohol syndrome
      (FAS) prevention is clear: If you are pregnant, don't drink; and if you drink,
      don't get pregnant. PH's message regarding neural tube defect (NTD) prevention is
      equally clear: all women of childbearing age who are capable of becoming pregnant
      should consume 0.4 mg of folic acid daily to reduce the risk of NTDs. In the
      past, issues such as eugenics, abortion of affected fetuses, and a lack of
      methods for the primary prevention of birth defects and genetic disorders have
      caused GHC providers to perform genetic counseling according to the two tenets
      mentioned above. Clearly, there are no moral or ethical reasons why children who
      are at risk for FAS, NTDs, fetal rubella syndrome, or many other conditions
      should not have the opportunity to be born healthy. Also, we know of no laws that
      prohibit providers from telling a woman to do something to improve her baby's
      chance of being born healthy. In our opinion, it is time for prenatal GHC
      professionals to re-examine the two tenets noted above on a case-by-case basis to
      determine when it is appropriate to use directive counseling techniques to
      improve reproductive outcomes in accordance with the goals of PH. A framework is
      provided here that could serve as: (1) a guide for future discussions dealing
      with these issues, and (2) a method to ensure that prenatal GHC policy and
      practice regarding these issues conform with one another.

PMID- 10943803
TI  - Labeling effects of a controversial psychiatric diagnosis: a vignette experiment
      of late luteal phase dysphoric disorder.
AB  - During the 1990s debate arose about the inclusion of Late Luteal Phase Dysphoric
      Disorder in the fourth edition of the American Psychiatric Association's
      Diagnostic and Statistical Manual. Opponents argued that the inclusion of this
      category would increase stigma and be used as a legal defense for child abuse and
      other violent crimes. Proponents argued that it would decrease stigma and enhance
      treatment seeking. Using an experimental vignette design, we tested these
      propositions in a study of 307 men and women living in Putnam County, New York.
      In general, the results do not indicate a pervasive negative impact of this
      label. On the other hand, labeling the disorder a "psychiatric condition" did
      increase recommendations for psychiatric help.

PMID- 10943804
TI  - Black and White women's weight-related attitudes and parental criticism of their
      childhood appearance.
AB  - Black (27%) and White (73%) women (n = 215) completed a survey assessing weight
      concern, ideal body size beliefs, body dissatisfaction, attitudes toward
      overweight body size, and parental criticism of their childhood appearance. Sixty
      four percent of the women reported they were currently trying to lose weight and
      63% desired a body size thinner than their own. High weight concern and negative
      attitudes toward overweight persons were reported, respectively, by 45% and 17%,
      of the women. The only significant difference found by race was weight concern as
      White women rated this significantly higher than Black women. No significant
      frequencies of choice were associated with the women's socioeconomic level. Self
      reported ratings of weight concern were significant and positively associated
      with those for body dissatisfaction, negative attitudes toward overweight
      persons, negative attitudes toward one's own overweight, and criticism of
      childhood appearance by mothers or fathers.

PMID- 10943805
TI  - The social and medical construction of lactation pathology.
AB  - Beginning in the 1880s, many mothers reported breastfeeding difficulties. Doctors
      blamed the stress of urban life. The "bad" human milk invariably produced by the
      mammary glands of urban women, some physicians charged, harmed babies as surely
      as the dirty and adulterated cow's milk common to the late nineteenth-century
      city. Mothers and pediatricians proved unusually susceptible to believing this
      allegation. Mothers, just learning about the germ theory of disease and anxious
      about protecting their babies from unseen microbes, found themselves gratefully
      relying on "scientific" food rather than on their own, apparently faulty, bodies.
      And pediatricians no longer had to defend their new specialty. Now they could
      point to the need for improved artificial food-given women's growing inability to
      lactate-as one justification for their specialty's existence. Under the influence
      of these mothers and doctors, the notion that human lactation is an unreliable
      body function became a cultural truth that has persisted unabated to the present
      day.

PMID- 10943806
TI  - Hostility and the cardiovascular reactivity of women during interpersonal
      confrontation.
AB  - In order to explore the association between hostility and women's health, this
      study examined the relationship of hostility to cardiovascular reactivity during
      stressful, interpersonal confrontations. Prior to the task, each participant's
      level of hostility, methods of coping with stress, and perceived social support
      were evaluated. Blood pressure and heart rate were monitored in ninety females
      during two discussions with a disagreeing confederate. In one discussion,
      participants were given positive feedback concerning their performance, while in
      a second discussion, participants were given non-positive feedback concerning
      their effectiveness in expressing their viewpoint. The results indicate that low
      hostile women displayed greater systolic blood pressure and heart rate increases
      than high hostile women during the discussions. In addition, participants
      exhibited greater systolic blood pressure and diastolic blood pressure reactivity
      during the positive feedback condition than during the non-positive feedback
      condition. However, for diastolic blood pressure, these results were qualified by
      an interaction, such that low hostile women displayed greater reactivity during
      the positive feedback condition than during the non-positive feedback condition,
      while high hostile women were equally reactive in both feedback conditions. State
      assessment of coping styles indicated that high hostile women may be less
      reactive due to withdrawal and lack of engagement during the task, while low
      hostile women may show greater engagement, especially when encouraged by positive
      feedback.

PMID- 10943807
TI  - Recent review of complementary and alternative medicine used by adolescents.
AB  - In the past decade the use of complementary and alternative medicine (CAM) has
      dramatically increased in adult, adolescent, and pediatric populations in the
      United States, Canada, and Western Europe. There are multiple reasons for this,
      including the search for natural therapies, curative and ameliorative therapies
      for chronic illnesses that are unresponsive to conventional therapy, attraction
      to therapists or alternative modalities suggested by friends, and the autonomy of
      obtaining unregulated products and services. This review will address recent
      studies concerning adolescent use of specific CAM therapies for asthma, urinary
      tract infections, headaches, dietary supplements in athletes, and mental health
      conditions. Health care providers need to be aware of the CAM therapies their
      patients are using, the potential side effects, and the possibilities for
      including effective complementary therapies into the conventional care they
      provide.

PMID- 10943808
TI  - Update of nutrition guidelines for the teen: trends and concerns.
AB  - Sociocultural influences are known to affect adolescent eating patterns and
      behaviors. Some teens reject a meat-based diet to become vegetarians; others take
      up dieting to lose weight or develop an eating disorder. Teens require increased
      nutrients to provide for the accelerated growth that takes place during these
      years. Nutritional deficiencies in adolescence can lead to loss of height,
      osteoporosis, and delayed sexual maturation. Sports also play an important role
      in many teens' lives. The desire to excel can lead to increased training and
      prolonged periods of dieting. Disordered eating, amenorrhea, and osteoporosis
      describe the "female athlete triad." Although more frequently seen in girls, boys
      who participate in sports that have an emphasis on size and weight such as
      wrestling and body building are also at risk for subclinical eating disorders.
      This paper discusses issues surrounding restrictive and nonrestrictive food
      patterns of adolescents and their nutritional consequences.

PMID- 10943809
TI  - Type 2 diabetes mellitus in adolescents.
AB  - Type 2 diabetes mellitus, a significant cause of adult morbidity and mortality,
      is being diagnosed more frequently in children and adolescents. Genetic
      predisposition and environmental factors are important determinants for the
      expression of this disease. Blacks, Hispanic Americans, and Native Americans are
      known to be at higher risk for type 2 diabetes mellitus as adults and there
      appears to be increased prevalence of the disease in adolescent members of these
      groups. Obesity, sedentary lifestyle, and high-fat diet are associated with type
      2 diabetes mellitus. A combination of peripheral insulin resistance and relative
      insulin deficiency results in chronic hyperglycemia. The onset of hyperglycemia
      is usually slow and symptoms such as polyuria and polydipsia are often subtle and
      may go unrecognized by the patient. The treatment of children and adolescents
      with type 2 diabetes mellitus is an area of active study. Programs targeting diet
      modification and increased physical activity are being developed in hopes of
      delaying or preventing the onset of disease. This paper examines risk factors for
      the development of type 2 diabetes mellitus, reviews diagnostic criteria, and
      discusses newly established screening criteria for type 2 diabetes mellitus in
      children and adolescents.

PMID- 10943810
TI  - Assessment of attention deficit hyperactivity disorder: a review of recent
      literature.
AB  - Attention deficit hyperactivity disorder is one of the most common behavioral
      disorders of childhood and is frequently assessed and treated by pediatricians
      and other primary care physicians. The diagnosis of attention deficit
      hyperactivity disorder is based on the careful synthesis of clinical data derived
      from multiple sources, notably, the patient, parents, and teachers. Standard
      behavioral rating scales simplify and standardize collection of clinical data but
      by themselves are not sufficient for a diagnosis. Recognition and treatment of
      disorders comorbid with attention deficit hyperactivity disorder are necessary
      for optimal outcomes. Psychoeducational testing is useful in the assessment of
      suspected associated learning disabilities, but there is no evidence at present
      to support use of psychologic testing, laboratory measures of attention,
      electroencephalography, or neuroimaging studies in the clinical assessment of
      attention deficit hyperactivity disorder.

PMID- 10943811
TI  - Obsessive compulsive disorder in childhood.
AB  - Obsessive compulsive disorder (OCD) involves obsessions and compulsions that
      cause impairment and distress, and which interfere with children's developmental
      adaptation and daily functioning. Furthermore, OCD often disrupts peer and family
      relationships and school performance and may compromise physical health. Once
      considered rare, recent epidemiologic studies report prevalence rates ranging
      from 1% in prepubertal children to 4% in adolescents. In addition, children with
      OCD are at high risk for comorbid psychopathology. Recent theoretic formulations
      for OCD encourage the integration of both psychological and biological
      perspectives. To fully understand the cause and course of OCD, integrated
      assessment of psychological and biological vulnerability as well as prospective
      longitudinal studies are needed.

PMID- 10943812
TI  - Depression and asthma in children.
AB  - Genetic vulnerability, allergic sensitivity, immunological compromise, and
      psychological stressors all contribute to the onset and severity of asthma. When
      depression decreases compliance and worsens prognosis, caring for an asthmatic
      child becomes even more problematic. Early intervention to address comorbid
      depressive disorders increases compliance, improves outcome, and allows a child
      to continue to appropriately to meet developmental expectations. In cases of
      severe asthma, treatment of depression may also decrease mortality.

PMID- 10943813
TI  - Children of alcoholics: an update.
AB  - One of four children in the United States lives in a family in which the child is
      exposed to alcoholism. Children of alcoholics (COAs) are two to ten times more
      likely to develop alcoholism than non-COAs. This paper reviews studies that have
      attempted to identify risk factors that mediate the increased vulnerability and
      the protective factors that moderate the risk. Factors discussed include parental
      antisocial personality disorder, externalizing behavior, internalizing symptoms,
      differential response to the effects of alcohol, and positive and negative
      alcohol-related expectancies. The heterogeneous nature of COAs is emphasized, and
      some of the challenges related to treatment and prevention are discussed.

PMID- 10943814
TI  - Diaper dermatitis and advances in diaper technology.
AB  - During the last decade, a number of technological innovations in disposable
      diaper designs and materials have aimed at reducing dermatological problems in
      the diaper area. The introduction of absorbent gelling materials led to a
      decrease in skin overhydration and made possible a more beneficial pH in the
      diaper area. A retrospective evaluation of clinical studies conducted before and
      after the introduction of absorbent gelling materials confirms that utilization
      of these materials has been associated with a marked reduction in the severity of
      diaper dermatitis. More recently, a novel diaper designed to deliver
      dermatological formulations to the skin also appears to improve the condition of
      diapered skin. Disposable wipes now are available that are nonirritating and
      suitable for use on damaged or broken skin. Ongoing innovative efforts in this
      area promise to further decrease the prevalence of diaper-associated dermatologic
      conditions.

PMID- 10943815
TI  - Molecular genetics in pediatric dermatology.
AB  - The field of pediatric dermatology continues to be enriched by the insights
      offered through molecular genetics. For some genetic skin disorders, including
      neurofibromatosis, tuberous sclerosis complex, and several forms of epidermolysis
      bullosa, genetic research has resulted in an evolving understanding of the
      relationship between genotype and phenotype, with the ability to predict some of
      the features of these disorders on the basis of the genetic defect. However,
      widespread use of molecular genetics for diagnostic testing of these disorders
      has not been possible because of genetic heterogeneity, limited availability, and
      reduced sensitivity. The appropriate use of genetic services is emphasized in
      this, the molecular era.

PMID- 10943816
TI  - Pigmentary disorders: update on neurofibromatosis-1 and tuberous sclerosis.
AB  - Pigmentary disorders are a common finding in primary care pediatric practice.
      Tuberous sclerosis and neurofibromatosis type 1 are two pigmentary disorders that
      have had many changes in their diagnostic and therapeutic approach. This review
      focuses on the significant advances in the past few years in the genetics and
      diagnostic criteria of these disorders. A review of the clinical presentation of
      neurofibromatosis is provided along with the revised diagnostic criteria for
      tuberous sclerosis. A logical approach to testing the tuberous sclerosis patient
      and his or her family is included.

PMID- 10943817
TI  - Update on selected viral exanthems.
AB  - Viral exanthems are common in childhood and account for a large number of patient
      visits to pediatric or family medicine clinics. Most exanthems are virtually
      harmless to the healthy child, but others can be signs of more significant
      systemic disease. Some exanthems that are benign or self-limited in the healthy
      child may propose significant risk to pregnant or immunocompromised individuals.
      Therefore, recognition of exanthems, which may be associated with certain viral
      illnesses, is important for the primary care provider. For example, prompt
      recognition of a viral exanthem caused by parvovirus may allow a pregnant female
      from exposing her fetus to a potentially fatal infection, or, if the exposure has
      already occurred, may indicate the need for appropriate fetal monitoring. In this
      manuscript, we review the recent literature pertaining to four characteristic
      exanthems that are thought to be viral in nature: papular purpuric gloves and
      socks syndrome; pityriasis rosea; unilateral lateral thoracic exanthem; and
      Gianotti-Crosti syndrome.

PMID- 10943818
TI  - What's new in human papillomavirus infection.
AB  - Warts continue to be a therapeutic challenge, especially widespread warts on
      children. A single, most effective treatment has not been defined. Conventional
      methods attempt to nonspecifically destroy infected tissue. Most of these
      procedures are painful, poorly tolerated by children, and often require multiple
      treatments. The efficacy of destructive techniques is impossible to verify in
      controlled clinical trials. Uncontrolled success rates are suboptimal and often
      no better than that seen with placebos. Alternative pharmacologic approaches have
      been designed to stimulate immunologic responses or provide anti-viral activity.
      Further study is needed to establish efficacy of these treatments.

PMID- 10943819
TI  - Endocrine and metabolism: 2000.

PMID- 10943820
TI  - Disorders of thyrotropin synthesis, secretion, and function.
AB  - Advances related to thyrotropin during 1999 included better understanding of the
      genetic basis of pituitary development and genetic advances in identifying
      clinical entities and their mechanisms and enabling new therapies. Initial
      clinical use of recombinant thyrotropin in evaluation of thyroid cancer
      recurrence was described. The importance of glycosylation pattern was clarified
      including the role of thyrotropin-releasing hormone in synthesis of thyrotropin
      molecules with mature glycosylation, and the impact of abnormal glycosylation in
      loss-of-function and gain-of-function mutations of the thyrotropin receptor.
      Causes of excessive thyrotropin secretion were evaluated, including pituitary
      thyrotropin-secreting adenomas. The fairly common causes of central
      hypothyroidism including ischemic injury, cranial irradiation, psychiatric
      conditions, or medical illness were assessed. The action of thyrotropin at the
      thyroid cell was assessed as a growth factor and as an influence on tyrosine
      sulfate content of thyroglobulin. Such basic and clinical science advances are
      rapidly affecting clinical care.

PMID- 10943821
TI  - Sex steroid and growth hormone supplementation to enhance performance in
      adolescent athletes.
AB  - Ergogenic aids are taken to enhance energy utilization by producing more,
      controlling its use, or increasing mechanical efficiency. Most athletes are
      looking toward enhancing performance by proper training modalities and methods;
      however, some look to the biochemical route for a "quick fix." Thus, the use of
      chemical agents is on the rise. Herein is provided information on the anabolic
      androgenic agents androstenedione, dehydroepiandrosterone, and the "parent"
      compound, testosterone. The former two, at best, have equivocal activity, but
      testosterone is both anabolic and androgenic in doses that adolescents might
      receive. Growth hormone and insulin-like growth factor-1 are anabolic,
      nonandrogenic compounds with undoubted effects on the lean body mass compartment.
      Both are expensive, not readily available, and subject to the art of
      counterfeiting. Thus, very few data are available in non-growth hormone-deficient
      adolescents. The discussion of these agents ends with issues of fairness, ethics,
      and the message we attempt to project to our teenagers, whether athletes or not.

PMID- 10943822
TI  - Molecular and genetic bases for maturity onset diabetes of youth.
AB  - Maturity onset diabetes of youth (MODY) occurs in children, adolescents and young
      adults as a non-insulin-requiring form of diabetes mellitus that is inherited as
      an autosomal dominant trait. Maturity onset diabetes of youth in whites presents
      subtly similar to type 2 diabetes in adults. In contrast, a MODY variant that
      occurs in young blacks, termed atypical diabetes mellitus, presents as an acute
      onset form of diabetes. Months to years after diagnosis, atypical diabetes
      mellitus reverts to a noninsulin requiring course similar to MODY in whites. Five
      molecular causes for MODY have been identified: mutations in four transcription
      factors and mutations in one enzyme (glucokinase). Transcription factors regulate
      gene expression within cells. Mutations in hepatocyte nuclear factor-4alpha,
      hepatocyte nuclear factor-1alpha, insulin promoter factor-1 and hepatocyte
      nuclear factor-1beta, respectively, cause MODY1, MODY3, MODY4, and MODY5.
      Glucokinase is the glucosensor of the beta cell. MODY2 is caused by glucokinase
      mutations. Although testing for MODY mutations is only available in research
      laboratories, a careful history and review of the patient's clinical course can
      often allow the clinician to diagnose MODY. The diagnosis of MODY has
      implications for the clinical management of the patient's diabetes.

PMID- 10943823
TI  - Management of central isosexual precocity: diagnosis, treatment, outcome.
AB  - The diagnosis of central isosexual precocity, a condition much more common in
      girls than in boys, is currently viewed as a spectrum of disorders between
      isolated premature thelarche and borderline early puberty. In some countries, a
      trend may be seen toward onset of puberty at earlier ages. Integration of the
      clinical findings with bone age, pelvic echography, and hormonal data as well as
      follow-up ascertainment of progression of development is critical to define which
      patients should be proposed for therapy. The use of long-acting forms of
      gonadotropin-releasing hormone (GnRH) agonists may not be indicated in slowly
      progressive variants or borderline early puberty because they do not affect final
      height. Preservation of height potential is particularly obvious in precocious
      puberty starting at young ages. In some selected patients, associated growth
      hormone therapy may increase adult height but further studies are warranted. The
      psychosocial and behavioral correlates of precocious puberty are an important and
      under investigated area.

PMID- 10943824
TI  - Genetic studies in idiopathic short stature.
AB  - Idiopathic short stature (ISS) refers to a heterogeneous group of children with
      marked growth failure of unknown cause, and encompasses familial short stature
      and constitutional delay of growth. It has been postulated that specific genetic
      mutations may explain certain cases of growth failure. Some patients with growth
      hormone (GH) deficiency have mutations in the GH-releasing hormone receptor or GH
      gene, whereas patients with GH insensitivity syndrome have mutations in the GH
      receptor or insulin-like growth factor-I gene. It appears that heterozygous
      mutations of the GH receptor may cause partial GH insensitivity in a subset of
      patients with ISS. Defects in the short stature homeobox-containing gene (SHOX)
      in the pseudoautosomal region of the sex chromosomes may cause the growth failure
      seen in the Leri-Weill and Turner syndromes, and in some familial cases of ISS.
      Further research into stature-related genes will likely contribute to our
      understanding of this population.

PMID- 10943825
TI  - Management of central diabetes insipidus in infancy with low renal solute load
      formula and chlorothiazide.

PMID- 10943827
TI  - Bibliography. Current world literature. Adolescent medicine.

PMID- 10943828
TI  - Bibliography. Current world literature. Psychiatry.

PMID- 10943826
TI  - Neonatal jaundice, animal-induced injuries, and immunizations.
AB  - The authors describe current investigation and most recent developments in three
      areas of pediatrics commonly faced by the office practitioner. The impetus of
      earlier newborn discharge places increased emphasis on pediatricians to
      accurately predict clinically significant jaundice. A better understanding of the
      pathophysiology of breastfeeding and breast milk jaundice, and the realization
      that Gilbert's syndrome may play a greater role in neonatal jaundice, only help
      confirm that the story of neonatal jaundice is still unfolding. Animal
      (particularly canine) bite injuries continue to be the most common animal-induced
      injuries, and a thorough review of appropriate antibiotic treatment and rabies
      prophylaxis guidelines are essential for the pediatric practitioner. During the
      past year, several major changes involving the use of rotavirus, pneumococcal,
      polio, meningococcal, and hepatitis A vaccines have taken place, which will have
      marked impact not only on pediatric office practice, but also on society as a
      whole.

PMID- 10943829
TI  - Bibliography. Current world literature. Dermatology.

PMID- 10943830
TI  - Bibliography. Current world literature. Endocrine and metabolism.

PMID- 10943831
TI  - Mergers and acquisitions: unequal partnerships in Drosophila myoblast fusion.

PMID- 10943832
TI  - The challenges of translating knockout phenotypes into gene function.

PMID- 10943833
TI  - The double lives of shuttling mRNA binding proteins.

PMID- 10943834
TI  - Transport across membranes: a question of navigation.

PMID- 10943835
TI  - A unified nomenclature system for the Drosophila odorant receptors. Drosophila
      Odorant Receptor Nomenclature Committee.

PMID- 10943836
TI  - An olfactory sensory map in the fly brain.
AB  - We have isolated the "complete" repertoire of genes encoding the odorant
      receptors in Drosophila and employ these genes to provide a molecular description
      of the organization of the peripheral olfactory system. The repertoire of
      Drosophila odorant receptors is encoded by 57 genes. Individual sensory neurons
      are likely to express only a single receptor gene. Neurons expressing a given
      gene project axons to one or two spatially invariant glomeruli in the antennal
      lobe. The insect brain therefore retains a two-dimensional map of receptor
      activation such that the quality of an odor may be encoded by different spatial
      patterns of activity in the antennal lobe.

PMID- 10943837
TI  - Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory
      of motor axons in the vertebrate limb.
AB  - Motor neurons extend axons along specific trajectories, but the molecules that
      control their pathfinding remain poorly defined. We show that two LIM homeodomain
      transcription factors, Lim1 and Lmx1b, control the initial trajectory of motor
      axons in the developing mammalian limb. The expression of Lim1 by a lateral set
      of lateral motor column (LMC) neurons ensures that their axons select a dorsal
      trajectory in the limb. In a complementary manner, the expression of Lmx1b by
      dorsal limb mesenchymal cells controls the dorsal and ventral axonal trajectories
      of medial and lateral LMC neurons. In the absence of these two proteins, motor
      axons appear to select dorsal and ventral trajectories at random. Thus, LIM
      homeodomain proteins act within motor neurons and cells that guide motor axons to
      establish the fidelity of a binary choice in axonal trajectory.

PMID- 10943838
TI  - Genetic evidence for selective transport of opsin and arrestin by kinesin-II in
      mammalian photoreceptors.
AB  - To test whether kinesin-II is important for transport in the mammalian
      photoreceptor cilium, and to identify its potential cargoes, we used Cre-loxP
      mutagenesis to remove the kinesin-II subunit, KIF3A, specifically from
      photoreceptors. Complete loss of KIF3A caused large accumulations of opsin,
      arrestin, and membranes within the photoreceptor inner segment, while the
      localization of alpha-transducin was unaffected. Other membrane, organelle, and
      transport markers, as well as opsin processing appeared normal. Loss of KIF3A
      ultimately caused apoptotic photoreceptor cell death similar to a known opsin
      transport mutant. The data suggest that kinesin-II is required to transport opsin
      and arrestin from the inner to the outer segment and that blocks in this
      transport pathway lead to photoreceptor cell death as found in retinitis
      pigmentosa.

PMID- 10943839
TI  - Drosophila dumbfounded: a myoblast attractant essential for fusion.
AB  - Aggregation and fusion of myoblasts to form myotubes is essential for myogenesis
      in many organisms. In Drosophila the formation of syncytial myotubes is seeded by
      founder myoblasts. Founders fuse with clusters of fusion-competent myoblasts.
      Here we identify the gene dumbfounded (duf) and show that it is required for
      myoblast aggregation and fusion. duf encodes a member of the immunoglobulin
      superfamily of proteins that is an attractant for fusion-competent myoblasts. It
      is expressed by founder cells and serves to attract clusters of myoblasts from
      which myotubes form by fusion.

PMID- 10943840
TI  - A role for hematopoietic stem cells in promoting angiogenesis.
AB  - Angiogenesis is an important event for embryonic organogenesis as well as for
      tissue repair in the adult. Here, we show that hematopoietic stem cells (HSCs)
      play important roles for angiogenesis during embryogenesis. To investigate the
      role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient
      embryos, which lack definitive hematopoiesis. These embryos showed defective
      angiogenesis in the head and pericardium. Para-aortic splanchnopleural (P-Sp)
      explant cultures on stromal cells (P-Sp culture) did not generate definitive
      hematopoietic cells and showed defective angiogenesis in the AML1 null embryo.
      Disrupted angiogenesis in P-Sp cultures from AML1 null embryos was rescued by
      addition of HSCs or angiopoietin-1 (Ang1). HSCs, which express Ang1, directly
      promoted migration of ECs in vivo and in vitro. These results indicate that HSCs
      are critical for angiogenesis.

PMID- 10943841
TI  - The EGF receptor provides an essential survival signal for SOS-dependent skin
      tumor development.
AB  - The EGF receptor (EGFR) is required for skin development and is implicated in
      epithelial tumor formation. Transgenic mice expressing a dominant form of Son of
      Sevenless (SOS-F) in basal keratinocytes develop skin papillomas with 100%
      penetrance. However, tumor formation is inhibited in a hypomorphic (wa2) and null
      EGFR background. Similarly, EGFR-deficient fibroblasts are resistant to
      transformation by SOS-F and rasV12, however, tumorigenicity is restored by
      expression of the anti-apoptotic bcl-2 gene. The K5-SOS-F papillomas and primary
      keratinocytesfrom wa2 mice display increased apoptosis, reduced Akt
      phosphorylation and grafting experiments imply a cell-autonomous requirement for
      EGFR in keratinocytes. Therefore, EGFR functions as a survival factor in
      oncogenic transformation and provides a valuable target for therapeutic
      intervention in a broader range of tumors than anticipated.

PMID- 10943842
TI  - Requirement for p38alpha in erythropoietin expression: a role for stress kinases
      in erythropoiesis.
AB  - Activity of the p38alpha MAP kinase is stimulated by various stresses and
      hematopoietic growth factors. A role for p38alpha in mouse development and
      physiology was investigated by targeted disruption of the p38alpha locus. Whereas
      some p38alpha(-/-) embryos die between embryonic days 11.5 and 12.5, those that
      develop past this stage have normal morphology but are anemic owing to failed
      definitive erythropoiesis, caused by diminished erythropoietin (Epo) gene
      expression. As p38alpha-deficient hematopoietic stem cells reconstitute lethally
      irradiated hosts, p38alpha function is not required downstream of Epo receptor.
      Inhibition of p38 activity also interferes with stabilization of Epo mRNA in
      human hepatoma cells undergoing hypoxic stress. The p38alpha MAP kinase plays a
      critical role linking developmental and stress-induced erythropoiesis through
      regulation of Epo expression.

PMID- 10943843
TI  - The Sec61p complex mediates the integration of a membrane protein by allowing
      lipid partitioning of the transmembrane domain.
AB  - We have investigated how the transmembrane (TM) domain of a membrane protein is
      cotranslationally integrated into the endoplasmic reticulum. We demonstrate that
      the Sec61p channel allows the TM domain to bypass the barrier posed by the polar
      head groups of the lipid bilayer and come into contact with the hydrophobic
      interior of the membrane. Together with the TRAM protein, Sec61p provides a site
      in the membrane, at the interface of channel and lipid, through which a TM domain
      can dynamically equilibrate between the lipid and aqueous phases, depending on
      the hydrophobicity of the TM domain and the length of the polypeptide segment
      tethering it to the ribosome. Our results suggest a unifying, lipid-partitioning
      model which can explain the general behavior of hydrophobic topogenic sequences.

PMID- 10943844
TI  - Zip3 provides a link between recombination enzymes and synaptonemal complex
      proteins.
AB  - In budding yeast, absence of the meiosis-specific Zip3 protein (also known as
      Cst9) causes synaptonemal complex formation to be delayed and incomplete. The
      Zip3 protein colocalizes with Zip2 at discrete foci on meiotic chromosomes,
      corresponding to the sites where synapsis initiates. Observations suggest that
      Zip3 promotes synapsis by recruiting the Zip2 protein to chromosomes and/or
      stabilizing the association of Zip2 with chromosomes. Zip3 interacts with a
      number of gene products involved in meiotic recombination, including proteins
      that act at both early (Mre11, Rad51, and Rad57) and late (Msh4 and Msh5) steps
      in the exchange process. We speculate that Zip3 is a component of recombination
      nodules and serves to link the initiation of synapsis to meiotic recombination.

PMID- 10943845
TI  - BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin
      remodeling to breast cancer.
AB  - Germline mutations in the tumor suppressor gene, BRCA1, predispose individuals to
      breast and ovarian cancers. Using a combination of affinity- and conventional
      chromatographic techniques, we have isolated a predominant form of a multiprotein
      BRCA1-containing complex from human cells displaying chromatin-remodeling
      activity. Mass spectrometric sequencing of components of this complex indicated
      that BRCA1 is associated with a SWI/SNF-related complex. We show that BRCA1 can
      directly interact with the BRG1 subunit of the SWI/SNF complex. Moreover, p53
      mediated stimulation of transcription by BRCA1 was completely abrogated by either
      a dominant-negative mutant of BRG1 or the cancer-causing deletion in exon 11 of
      BRCA1. These findings reveal a direct function for BRCA1 in transcriptional
      control through modulation of chromatin structure.

PMID- 10943846
TI  - Temporal and spatial regulation of expression of two galectins during kidney
      development of the chicken.
AB  - Organogenesis and the establishment of the mature phenotype require an interplay
      between diverse recognition systems. Concerning protein-carbohydrate
      interactions, galectins are known to be involved in several extra- and
      intracellular functions. Due to the occurrence of two avian galectins in liver
      (chicken galectin-16 CG-16) and intestine (chicken galectin-14; CG-14) with
      different developmental regulation. the questions addressed are to what extent
      and where these galectins are present during chicken kidney development. Using
      Western blot analysis, the presence of both activities in tissue extracts was
      ascertained. A solid-phase assay showed peak levels at day 12 followed by a
      decline. A histochemical analysis was carried out in combination with routine
      staining. Epithelial cells of the mesonephric proximal tubules were
      immunoreactive in the cytoplasm for CG-14 from day 5 of incubation onwards.
      Additionally, epithelial cells of the metanephric collecting ducts were stained.
      For CG-16 a rather similar pattern of staining was seen, additional positivity in
      early glomerular podocytes being notable. At the electron microscopical level, a
      diffuse staining for CG-14 was seen in the cytoplasm, whereas immunoreactivity
      for CG-16 was observed mainly in mitochondria. These results demonstrate
      quantitative differences in the developmental regulation of the two avian
      galectins with obvious similarities in the cell-type pattern but with a disparate
      intracellular localisation profile.

PMID- 10943847
TI  - Long-term effect of vital labelling on mixed Schwann cell cultures.
AB  - Schwann cell transplantation following neuronal injury could encourage
      regeneration of spinal cord as well as improving peripheral nerve gap repair. In
      order to gain a better understanding of the role of transplanted Schwann cells in
      vivo, it is essential to be able to follow their behaviour after transplantation.
      Our aim was to evaluate the suitability of two vital fluorescent labels on the
      proliferation rate and phenotypic stability of Schwann cells, in either pure
      culture or mixed co-culture. Primary cultures of Schwann cells were obtained from
      Dark Agouti and Lewis neonatal rats and labelled with H33342 and PKH26,
      respectively. In mixed cultures, a 50: 50 mixture of Dark Agouti and Lewis
      Schwann cells was present. Labelled cultured cells were examined at 1, 2 and 4
      weeks for viability and phenotypic marker expression of S100, GFAP, p75, MHC I,
      MHC II and compared with corresponding unlabelled cells. The results showed that
      although there was no deleterious interaction in the mixed cultures, the
      viability was reduced by the labelling after 2 weeks. Labelled cells could be
      distinguished up to 4 weeks, but there was leakage of H33342 label after 2 weeks.
      Labelled Schwann cells showed reduced expression of phenotypic markers,
      especially p75 when labelled with H33342. In conclusion, H33342 and PKH26 can be
      used as fluorescent markers of Schwann cells for short-term studies, for a
      maximum of 2 weeks, but different markers may be needed for longer experiments.

PMID- 10943848
TI  - Expression of leukaemia inhibitory factor during the development of the human
      enteric nervous system.
AB  - Leukaemia inhibitory factor (LIF) is a neuropoietic cytokine, which promotes the
      development of enteric neurons in vitro, particularly when administered together
      with neurotrophin-3 (NT-3). The purpose of this study was to map the LIF
      immunoreactivity in the human enteric nervous system in foetuses, children,
      adults, and in patients with Hirschsprung's disease. Normal bowel specimens were
      obtained at postmortem examination of 13 foetuses, at 13-31 weeks of gestation,
      and at surgery in five children and two adults. Bowel resected in seven patients
      with Hirschsprung's disease was also investigated. Immunohistochemical analysis
      was performed on material fixed in formalin and embedded in paraffin. The
      specimens were exposed to antibodies raised against LIF. The ABC-complex method
      was used to visualise binding of antibodies to the corresponding antigen. LIF
      immunoreactivity was disclosed in the myenteric and submucous ganglion cells at
      13-31 weeks of gestation, in childhood cases, and adults. LIF-immunoreactive
      ganglion cells were absent in aganglionic bowel, where the ganglia in the
      intermuscular layer were replaced by hypertrophic nerve bundles. These
      morphological findings indicate that LIF may play a role in the development of
      the enteric nervous system.

PMID- 10943849
TI  - Age-related changes and location of types I, III, XII and XIV collagen during
      development of skeletal muscles from genetically different animals.
AB  - The ontogenesis of total collagen and of different collagen types was studied in
      four muscle types from genetically different cattle. Hydroxyproline content was
      1.2-fold higher in muscles from cross-bred foetuses with normal muscle growth
      compared to those of the other genetic types (pure bred with different growth
      rates, double-muscled breed). A similar tendency was observed for type III
      collagen content. In all muscles of each animal studied, type XII and XIV
      collagens were colocated in perimysium. Immunolabelling obtained for type XII
      collagen was higher during foetal life than after birth, while for type XIV
      collagen, the opposite result was obtained. Whatever the muscle studied, but
      especially in semitendinosus muscle, during the foetal and the post-natal period
      until 15 months of age, immunolabelling with antibody anti-type XIV collagen
      tended to be more intense in muscles of animals from fathers selected for a low
      muscle growth capacity compared to those from fathers selected for a high muscle
      growth capacity. In conclusion, this study shows, that during foetal life,
      selection according to muscle growth capacity has no significant effect on the
      contents of total hydroxyproline or type III collagen, but minor effects on
      collagen localization.

PMID- 10943850
TI  - Changes in growth factor expression in the ageing prostate may disrupt epithelial
      stromal homeostasis.
AB  - The alterations in expression of six growth factors known to be regulators of
      prostatic function have been examined in the ventral lobe of prostates from young
      adult (14 week) and ageing (1.5 year) Wistar rats. The selected growth factors
      were transforming growth factor beta (TGFbeta1), insulin-like growth factor I
      (IGF-I), insulin-like growth factor II (IGF-II), platelet derived growth factor
      (PDGF), basic fibroblast growth factor (FGF2) and epidermal growth factor (EGF).
      The extracellular matrix growth co-factor thrombospondin (TSP) was also examined.
      Our study demonstrated a 2.9-fold up-regulation of TGFbeta1 (p < 0.0001), a 2.0
      fold increase in FGF2 (p < 0.0002), an 8.3-fold increase in IGF-II (p < 0.0007)
      and a 5.4-fold increase in EGF (p < 0.0001) in ageing compared to adult prostate
      tissue. Conversely, we observed a 2.7-fold down-regulation of IGF-I (p < 0.0005),
      a 1.7-fold decrease in PDGF (p < 0.0097) and a 5.8-fold decrease in TSP (p <
      0.0079) in ageing rat prostate tissue. The observed alterations in growth factor
      expression in this study may be the result or cause of, an imbalance in the
      proliferative-apoptotic balance during ageing. This imbalance may explain the
      increase in epithelial proliferation that is characteristic of the normal ageing
      prostate. As in other systems it seems likely that these factors work
      synergistically rather than in isolation.

PMID- 10943852
TI  - Endometrial cell death during early pregnancy in the rat.
AB  - In a study of early pregnancy in the rat, a high proportion of morphologically
      apoptotic, TUNEL and P2X7 positive cells were found to be present in the luminal
      epithelium and stroma prior to implantation. At the time of implantation on Day
      6, apoptosis as measured by these indicators was reduced up to 4-fold in the non
      implantation uterine epithelium but was markedly increased adjacent to the
      implanting blastocyst. It is proposed that apoptotic cell death is an important
      regulatory factor involved in uterine remodelling prior to and during
      implantation.

PMID- 10943851
TI  - Distributional changes of purinergic receptor subtypes (P2X 1-7) in uterine
      epithelial cells during early pregnancy.
AB  - Expression of each of the purinergic receptor subtypes (P2X7) was studied by
      immunohistochemical localization in the apical, lateral and basal plasma
      membranes of rat uterine epithelial cells during early pregnancy to the time of
      implantation on Day 6. Labelling for each P2X subtype was seen in the apical,
      lateral and basal compartments on Days 1 and 3, except for P2X2 which was only
      observed in the basement membrane. The P2X5 signal was similar in temporal and
      spatial expression to the other subtypes, but with a greatly reduced intensity.
      At the time of implantation on Day 6, this pattern altered dramatically. Apical
      expression markedly increased for most subtypes while the lateral and basal
      signals were markedly reduced. The exceptions to this pattern were P2X2, which
      displayed both a strong basal and apical label, and P2X4 which became de
      expressed in all areas. We propose that the changing spatial and temporal
      expression of the P2X receptors is a significant factor in the regulation of
      events during early pregnancy. They are expressed in the same location as
      remodelling. apoptosis, and protein activation events prior to implantation on
      Day 6. These observations suggest an up-regulation of calcium-mediated events,
      including cytoskeletal alterations, a decrease in luminal pH and transmembrane
      molecule activation.

PMID- 10943854
TI  - Remnants of suicidal cells fostering systemic autoaggression. Apoptosis in the
      origin and maintenance of autoimmunity.

PMID- 10943853
TI  - Heme oxygenase-2 and nitric oxide synthase immunoreactivity of bovine olfactory
      receptor neurons and a comparison with the distribution of NADPH-diaphorase
      staining.
AB  - It has recently been suggested that, in addition to nitric oxide (NO), carbon
      monoxide (CO) is an important gaseous messenger which might be involved in
      vertebrate olfactory transduction because its effects include activation of
      guanylyl cyclase and the formation of cGMP. As there is no information regarding
      the presence of heme oxygenase-2 -- the constitutive isoform of the heme
      oxygenase system -- in olfactory neurons of non-rodent species, we have
      investigated the distribution pattern of heme oxygenase-2 in the olfactory
      epithelium of the bovine, a representative of macrosmatics. Localization of
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity of the
      olfactory epithelium was compared with heme oxygenase-2 and NO synthase (NOS)
      immunoreactivities in order to obtain possible hints at functional significance.
      NADPH-d activity was particularly intense in apical dendrites of receptor
      neurons. It was also found in Bowman glands and intraepithelial duct cells. Less
      intense, discrete NADPH-d activity was present also at intermediate and basal
      levels of the olfactory epithelium, corresponding to the layer of receptor neuron
      somata and basal cells. While heme oxygenase-2 activity mainly occurred in
      neuronal perikarya, a very intense NOS immunoreactivity, exclusively for the
      inducible isoform, was detected in the apical dendrites. Ultrastructurally, NADPH
      d histochemistry showed distinct labelling of membranes, in particular of
      endoplasmic reticulum, mitochondria and nucleus. The coincident localization of
      the moderate NADPH-d activity and heme oxygenase-2 immunoreactivity in receptor
      cell perikarya suggest a functional association between NADPH-cytochrome P450
      reductase and heme oxygenase-2. In contrast, dendritic localization of NADPH-d
      activity is topically and possibly functionally related to the presence of the
      inducible isoform of NOS. The results suggest that both CO and NO may be
      generated in bovine receptor neurons and thus involved in odorant stimulation.
      Based on immunocytochemical localization of synthesizing enzymes, NO might be
      regarded as a direct regulator of transduction related processes while CO might
      act as a modulator of the initial signal.

PMID- 10943855
TI  - Clinical images: Maffucci's syndrome.

PMID- 10943856
TI  - Multipoint linkage analysis of a candidate gene locus in rheumatoid arthritis
      demonstrates significant evidence of linkage and association with the
      corticotropin-releasing hormone genomic region.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is the most common disabling autoimmune
      disease, affecting approximately 1% of the population. The disease etiology is
      unknown, but it involves inflammation and immune dysregulation and is influenced
      by genetic variation at both HLA and other, as-yet-unidentified genetic loci.
      Corticotropin-releasing hormone (CRH; or corticotropin-releasing factor), a
      primary regulator of the hypothalamic-pituitary-adrenal axis and a key element in
      the response to stress and inflammation, is a strong candidate gene for RA. We
      examined the role of DNA variation across the region containing this gene in
      multicase families with RA. METHODS: We genotyped fluorescently labeled simple
      tandem repeat genetic markers from chromosome 8q13 in 295 families with multiple
      cases of RA. Singlepoint and multipoint nonparametric linkage analysis and
      association analysis using transmission disequilibrium testing (TDT) were also
      used. RESULTS: Single-point linkage analysis using a microsatellite within 30 kb
      of the CRH locus (CRH.PCR at position 8q13) showed a significant excess of allele
      sharing in 295 United Kingdom RA families with at least 2 affected members
      (MapMaker/Sibs logarithm of odds [LOD] 1.4; P = 5.5x10(-3); mean identity by
      descent [ibd] sharing 55.9%). To provide a more detailed linkage map, a
      multipoint analysis was conducted with an additional 7 dinucleotide
      microsatellite markers (average heterozygosity 0.75) flanking the CRH locus.
      Significant linkage was detected over a 22-cM region between D8S285 and D8S530,
      with the maximum singlepoint LOD score of 1.77 at D8S1723 (MapMaker/Sibs P =
      2.2x10(-3); mean ibd sharing 59.3%). Multipoint analysis showed strongest
      evidence for linkage at the same marker (multipoint LOD 1.78, P = 2.1x10(-3),
      mean ibd sharing 55.8%). TDT analysis showed significant association at the CRH
      locus (P = 2.6x10(-3)). CRH has a sibling relative risk of 1.14, and contributes
      <10% to the sibling relative risk of RA. CONCLUSION: With the exception of HLA,
      this is the strongest evidence yet of a genetic locus that is both linked to and
      associated with RA, and provides an avenue for further genetic characterization
      and potentially novel therapeutic intervention.

PMID- 10943857
TI  - Mannose-binding lectin and rheumatoid arthritis in southern Chinese.
AB  - OBJECTIVE: Insufficiency of mannose-binding lectin (MBL) is associated with
      recurrent infections. Rheumatoid arthritis (RA) may represent an aberrant immune
      response to infections. This study examined the phenotypic expression and variant
      alleles of the MBL gene and its etiologic role in Chinese with RA. METHODS: We
      studied 211 RA patients and 196 healthy subjects. Serum MBL concentrations and
      codon-54 mutation of the MBL gene and its promoter polymorphisms were analyzed.
      Clinical characteristics and disease activity were also examined. RESULTS:
      Patients with RA had significantly lower serum MBL levels and higher frequency of
      codon-54 mutation of the MBL gene compared with controls. Additionally, there was
      a significant difference in the distribution of promoter polymorphisms, H/L,
      between RA patients and controls, although the frequencies of Y/X and those of
      nonstructural polymorphisms, P/Q, did not differ between the 2 groups.
      Furthermore, patients with RA had a lower incidence of the highest-producing
      haplotype HY and a higher incidence of the lowest-producing haplotype LX compared
      with controls. Serum MBL levels did not correlate with drug treatment or with
      disease activity. However, patients with erosive and serious extraarticular
      disease had significantly lower serum MBL levels than those without these disease
      manifestations at the time of study. Also, significantly more patients with
      erosive disease had a codon-54 mutation of the MBL gene compared with those with
      nonerosive disease. CONCLUSION: The codon-54 mutation and low-producing promoter
      polymorphisms of the MBL gene are associated with RA. A low serum level of MBL
      predisposes to the development of RA and is a risk factor for severe disease in
      southern Chinese.

PMID- 10943858
TI  - Adenovirus-mediated gene transfer of CTLA-4Ig fusion protein in the suppression
      of experimental autoimmune arthritis.
AB  - OBJECTIVE: Blockade of CD28-B7 interactions with soluble CTLA-4Ig fusion protein
      (which binds and blocks both B7-1 and B7-2 costimulatory molecules on antigen
      presenting cells) has been shown to ameliorate experimental autoimmune diseases
      such as lupus, experimental autoimmune encephalomyelitis, diabetes, and, in our
      laboratory, collagen-induced arthritis (CIA). Because prolonged inhibition of
      this costimulatory pathway may be required, and the adenovirus-mediated gene
      transfer technology is very efficient in achieving sustained expression of
      proteins in vivo, we examined the effects of adenovirally delivered CTLA-4Ig in
      established murine CIA. METHOD: Replication-deficient recombinant adenoviruses
      encoding a chimeric CTLA-4Ig fusion protein, or beta-galactosidase as control,
      were injected intravenously into male DBA/1 mice once at arthritis onset. Disease
      activity was monitored by the assessment of clinical score, paw thickness, and
      type II collagen (CII)-specific cellular and humoral responses for 3 weeks.
      Groups of mice were also serially injected with a CTLA-4Ig fusion protein and an
      anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody
      (mAb), and disease activity was compared with that in the adenovirally transfused
      groups. RESULTS: Both the adenovirally delivered and the recombinant CTLA-4Ig
      fusion protein suppressed established CIA, whereas anti-CTLA-4 mAb and the
      control beta-galactosidase adenovirus did not significantly affect the disease
      course. CII-specific lymphocyte proliferation, interferon-gamma production, and
      anti-CII antibody levels, both IgG1 and IgG2a, were significantly reduced by CTLA
      4Ig treatment. CONCLUSION: Blockade of the B7-CD28 costimulatory pathway by
      adenovirus-mediated CTLA-4Ig gene transfer is as effective as the recombinant
      fusion protein in treating established CIA, without the need for repeated
      administrations. Significant reduction in pathogenic cellular and humoral
      responses is achieved even after the onset of arthritis, thus suggesting the
      valuable therapeutic potential of this gene-transfer method in human rheumatoid
      arthritis.

PMID- 10943859
TI  - Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic
      cells or by naked DNA injection prevents the progression of collagen-induced
      arthritis.
AB  - OBJECTIVE: The complement system is important in the development of autoimmune
      inflammation, including rheumatoid arthritis (RA) and collagen-induced arthritis
      (CIA). Complement receptor 1 (CR1) is involved in regulation of complement
      activity. Studies on models of autoimmunity have demonstrated that soluble CR1
      (sCR1) is a potent therapeutic agent. The present study was thus undertaken to
      investigate the feasibility of antiinflammatory gene therapy to prevent CIA by
      delivery of genes encoding truncated sCR1 (tsCR1) and dimeric tsCR1-Ig. METHODS:
      Syngeneic fibroblasts or arthritogenic splenocytes, engineered to express tsCR1
      using retrovirus-mediated gene transfer, were injected into DBA/1 recipients that
      had been immunized with bovine type II collagen (CII). In separate experiments,
      naked DNA containing tsCR1 and tsCR1-Ig genes was injected intramuscularly into
      the immunized animals. The clinical development of arthritis was monitored, anti
      CII levels measured, and antigenic T cell response studied. Affinity-purified
      tsCR1-Ig was assayed for its inhibitory effect on the alternative complement
      pathway in mouse serum. RESULTS: Treatment of CII-immunized mice with the tsCR1
      expressing cells inhibited development of CIA, reduced anti-CII antibody levels,
      and inhibited T cell response to CII in vitro. Intramuscular injections of DNA
      encoding the CR1 genes prevented the progression of disease. Furthermore,
      compared with full-length sCR1, purified tsCR1-Ig was more active in inhibiting
      the murine alternative complement pathway. CONCLUSION: Our findings demonstrated
      that tsCR1 and tsCR1-Ig, when delivered via gene therapy, had a beneficial effect
      on autoimmune inflammation. These results indicate that targeting the complement
      system in RA patients may be of clinical importance.

PMID- 10943860
TI  - Cartilage degradation and invasion by rheumatoid synovial fibroblasts is
      inhibited by gene transfer of a cell surface-targeted plasmin inhibitor.
AB  - OBJECTIVE: Joint destruction in rheumatoid arthritis (RA) is a result of
      degradation and invasion of the articular cartilage by the pannus tissue. The
      present study was undertaken to examine the role of the plasminogen activation
      system in cartilage degradation and invasion by synovial fibroblasts and
      investigate a novel gene therapeutic approach using a cell surface-targeted
      plasmin inhibitor (ATF.BPTI). METHODS: Adenoviral vectors were used for gene
      transfer. The effects of ATF.BPTI gene transfer on RA synovial fibroblast
      dependent cartilage degradation were studied in vitro, and cartilage invasion was
      studied in vivo in the SCID mouse coimplantation model. RESULTS: The results
      indicate that cartilage matrix degradation by rheumatoid synovial fibroblasts is
      plasmin mediated and depends on urokinase-type plasminogen activator for
      activation. Targeting plasmin inhibition to the cell surface of the fibroblasts
      by gene transfer of a cell surface-binding plasmin inhibitor resulted in a
      significant reduction of cartilage matrix degradation in vitro and of cartilage
      invasion in vivo. Compared with uninfected rheumatoid synovial fibroblasts, the
      mean +/-SEM cartilage degradation in vitro was reduced to 87.9+/-0.9% after LacZ
      gene transfer versus a reduction to 24.0+/-1.6% after ATF.BPTI gene transfer
      (P<0.0001). The mean +/- SEM in vivo cartilage invasion score was 3.1+/-0.4 in
      the control-transduced fibroblasts and 1.8+/-0.4 in the ATF.BPTI-transduced
      fibroblasts (P<0.05). CONCLUSION: These results indicate a role of the
      plasminogen activation system in synovial fibroblast-dependent cartilage
      degradation and invasion in RA, and demonstrate an effective way to inhibit this
      by gene transfer of a cell surface-targeted plasmin inhibitor.

PMID- 10943861
TI  - Anti-interleukin-1 and anti-CD44 interventions producing significant inhibition
      of cartilage destruction in an in vitro model of cartilage invasion by rheumatoid
      arthritis synovial fibroblasts.
AB  - OBJECTIVE: To establish an in vitro model for the investigation of destructive
      processes in rheumatoid arthritis (RA), to study the interaction between
      fibroblasts, macrophages, and chondrocytes, and to evaluate strategies to inhibit
      joint destruction in RA. METHODS: Human and bovine chondrocytes cultured in
      sponges pretreated with native bovine embryonic extracellular matrix produced a
      cartilaginous matrix reflected by the incorporation of 35S into proteoglycans.
      The 3-dimensional culture system was optimized for the number of chondrocytes
      (10(5) cells/sponge), the timing of 35S incorporation (day 21 after chondrocyte
      isolation), and the medium (20% fetal calf serum). RA synovial fibroblasts (RASF;
      10(5)) were added, and the matrix destruction mediated by these RASF was
      monitored by the release of 35S. The system was modulated by the addition of
      monocytes (U937 cells), cytokines (interleukin-1beta [IL-1beta] and tumor
      necrosis factor alpha [TNFalpha]), interleukin-1 receptor antagonist (IL-1Ra),
      and monoclonal antibodies against IL-1beta and CD44. RESULTS: RASF destroyed the
      bovine cartilaginous matrix within 2 weeks (days 5-12) and the human
      cartilaginous matrix within 3 weeks (days 10-18). Compared with the effect of
      RASF alone (mean +/- SD 948 +/-180 counts per minute/week), the addition of U937
      cells (a monocytic cell line), IL-1beta, or TNFalpha to the incubation medium
      increased the destruction of human cartilaginous matrix by at least 71% up to 90%
      (ranging from 1,618+/-204 cpm/week to 1,802+/-307 cpm/week). IL-1Ra and anti-IL
      1beta monoclonal antibodies reduced the destruction of human matrix by 45% and
      35%, respectively; this was partially reversed by the addition of U937 cells. The
      pretreatment of RASF with anti-CD44 monoclonal antibody (an adhesion molecule and
      receptor for hyaluronic acid) inhibited the destruction of the cartilaginous
      matrix by an average of 41% over 3 weeks. CONCLUSION: This model is envisioned to
      study distinct aspects of human destructive joint diseases under in vitro
      conditions and to replace and/or supplement animal experiments in basic research
      and drug testing. Based on the fact that proinflammatory cytokines enhance
      destruction whereas IL-1Ra and antibodies against IL-1beta and CD44 inhibit the
      process, it is concluded that anti-IL-1- and anti-CD44-directed therapies may
      help prevent cartilage destruction in RA.

PMID- 10943862
TI  - Participation of transglutaminase in the activation of latent transforming growth
      factor beta1 in aging articular cartilage.
AB  - OBJECTIVE: Transglutaminase (TGase) catalyzes the calcium-dependent crosslinking
      of polypeptide chains, resulting in posttranslational protein modifications that
      affect both intracellular and extracellular processes. We previously demonstrated
      a dramatic elevation of TGase activity levels in aging articular chondrocytes and
      postulated a role for TGase in the pathologic processes common in aging joints.
      In several cell systems, TGase participates in the activation of latent
      transforming growth factor beta (LTGFbeta). Since TGFbeta is a key factor in age
      related cartilage diseases, the purpose of the present study was to determine
      whether TGase from aging articular chondrocytes participates in LTGFbeta
      activation. METHODS: We measured the ability of old and young porcine articular
      chondrocytes to activate 10 ng/ml of LTGFbeta1 in the presence and absence of
      TGase inhibitors. The activity of plasmin, another key participant in LTGFbeta
      activation, was also measured. RESULTS: Old chondrocytes activated 11+/-1.8%
      (mean +/- SD) of exogenous LTGFbeta1 at 6 hours, while young chondrocytes
      activated 4.2+/-0.5% of exogenous LTGFbeta1. The addition of 3 different TGase
      inhibitors suppressed active TGFbeta1 in the cell layer to levels that were 35
      69% of control values in old chondrocytes and had no effect on young
      chondrocytes. The ability to suppress TGFbeta activation correlated with the
      ability of each of the TGase inhibitors to inhibit TGase activity. The activity
      of plasmin, which enzymatically activates LTGFbeta1, did not differ between young
      and old chondrocytes and was unaffected by TGase inhibition. CONCLUSION: We
      report here a novel pathologic function for TGase in aging articular cartilage.
      This work supports a role for elevated TGase activity in age-related arthritis
      based in part on its participation in the activation of the critical growth
      factor TGFbeta in articular cartilage.

PMID- 10943863
TI  - Human chondrocytes express functional chemokine receptors and release matrix
      degrading enzymes in response to C-X-C and C-C chemokines.
AB  - OBJECTIVE: Human chondrocytes produce different C-X-C and C-C chemokines under
      basal conditions and upon activation with proinflammatory cytokines. We
      investigated whether human chondrocytes also have chemokine receptors and
      examined the effects of chemokines on chondrocyte activity. METHODS: The
      expression of chemokine receptors was determined by immunochemical analysis of
      frozen sections from normal and osteoarthritic cartilage and by flow cytometry of
      isolated cells. The messenger RNA expression for chemokine receptors was studied
      by reverse transcriptase-polymerase chain reaction. Isolated chondrocytes were
      stimulated with different chemokines, and the responses were evaluated by
      assaying the release of matrix metalloprotease 3 (MMP-3) and of the lysosomal
      enzyme N-acetyl-beta-D-glucosaminidase in the supernatants. RESULTS: A wide
      variety of chemokine receptors (CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, and CXCR-2)
      was detected on human chondrocytes. Interaction of these receptors with the
      corresponding ligands induced the release of MMP-3. This response was abrogated
      by pretreatment of the cells with Bordetella pertussis toxin, demonstrating
      involvement of G proteins of the Gi type. The response decreased in the presence
      of cycloheximide, indicating dependence on protein synthesis. Chemokines also
      induced the exocytosis of N-acetyl-beta-D-glucosaminidase, which was prevented by
      receptor blockage with anti-CCR-3 and by treatment with B pertussis toxin.
      Chondrocytes obtained from osteoarthritic tissue showed an increased expression
      of CCR-3 and possibly of CXCR-1, and an augmented release of matrix-degrading
      enzymes compared with chondrocytes from normal donors. CONCLUSION: Our findings
      suggest the existence in human chondrocytes of a novel catabolic pathway, primed
      by chemokines and their receptors, that leads to the breakdown of cartilage
      matrix components.

PMID- 10943864
TI  - Up-regulation of cartilage oligomeric matrix protein at the onset of articular
      cartilage degeneration in a transgenic mouse model of osteoarthritis.
AB  - OBJECTIVE: To investigate the suitability of cartilage oligomeric matrix protein
      (COMP) as a marker for articular cartilage degeneration in a transgenic mouse
      model of osteoarthritis (OA). METHODS: Northern blot analysis of total RNA
      extracted from the knee joints of transgenic Del1 mice, which harbor a short
      deletion in a type II collagen transgene, and of their nontransgenic littermates
      was used to monitor changes in COMP messenger RNA (mRNA) levels during cartilage
      degeneration. Immunohistochemistry was used to determine the distribution of COMP
      in articular cartilage, and serum levels of COMP were measured by immunoassay.
      RESULTS: Transient up-regulation of COMP mRNA was seen in articular cartilage of
      transgenic Del1 mice at the onset of OA lesions at the age of 3 months. Compared
      with nontransgenic controls, COMP immunostaining of articular cartilage in 3-9
      month-old transgenic mice was increased, especially at the border of uncalcified
      and calcified cartilage. There was also a change from predominantly
      interterritorial to pericellular/territorial deposition of COMP. This difference
      persisted until the age of 15 months, when the nontransgenic controls also
      demonstrated articular cartilage degeneration and increased COMP immunostaining.
      Increased serum levels of COMP were seen in Del1 mice at the age of 4 months,
      correlating temporally with the onset of cartilage degeneration. CONCLUSION:
      These findings suggest that upregulation of COMP mRNA and redistribution of the
      protein are characteristic of the early stages of articular cartilage
      degeneration in the transgenic mouse model in which OA results from a dominant
      negative mutation in the type II collagen gene. The data provide additional
      support for the notion that COMP is a useful marker for altered cartilage
      metabolism in developing OA.

PMID- 10943865
TI  - Association of giant cell arteritis and polymyalgia rheumatica with different
      tumor necrosis factor microsatellite polymorphisms.
AB  - OBJECTIVE: To determine whether giant cell arteritis (GCA) and polymyalgia
      rheumatica (PMR) are associated with different tumor necrosis factor (TNF)
      microsatellite polymorphisms. METHODS: Typing of TNF microsatellite polymorphisms
      was carried out by molecular-based techniques on DNA obtained from a population
      sample of residents from Lugo, northwestern Spain. A case-control approach was
      used to compare 136 patients with GCA and/or PMR with 147 ethnically matched
      controls. The association of disease with TNF microsatellite polymorphisms was
      investigated using chi-square tests and multivariate logistic regression
      analyses. RESULTS: Different TNF microsatellite associations were found with GCA
      and PMR. In patients with isolated GCA, the primary association was with TNFa2,
      which was independent of the GCA associations with HLA-DRB1*0401 and *0101. A
      negative association was found with TNFa10. In patients with isolated PMR, there
      was a positive association with TNFb3. This was found to be independent of the
      HLA-DRB1*13/*14 association in isolated PMR. TNFd4 was negatively associated with
      isolated PMR. Forward stepwise logistic regression analyses indicated that the
      strongest association with GCA was provided by the TNFa2 allele, although
      DRB1*0401 and *0101 were still associated. PMR was primarily associated with
      TNFb3. A direct comparison of TNF allele frequencies between isolated GCA and
      isolated PMR indicated that the main difference between these conditions occurred
      in the frequency of TNFa10. CONCLUSION: GCA and PMR in individuals from
      northwestern Spain are associated with different TNF microsatellite
      polymorphisms. The primary TNF associations (TNFa2 and TNFb3) appear to influence
      susceptibility to these conditions independent of any HLA-DRB1 association.

PMID- 10943866
TI  - Suppression of tumor necrosis factor alpha-induced matrix metalloproteinase 9
      production by the introduction of a super-repressor form of inhibitor of nuclear
      factor kappaBalpha complementary DNA into immortalized human salivary gland
      acinar cells. Prevention of the destruction of the acinar structure in Sjogren's
      syndrome salivary glands.
AB  - OBJECTIVE: We have previously shown that specific enhancement in acinar cells of
      proteolytic activity induced by tumor necrosis factor alpha (TNFalpha) may be
      responsible for the destruction of the acinar structure in the salivary glands of
      patients with Sjogren's syndrome. Because matrix metalloproteinase 9 (MMP-9) is
      regulated by nuclear factor kappaB (NF-kappaB), we investigated the effect of a
      super-repressor form of inhibitor of nuclear factor kappaBalpha (srIkappaBalpha)
      on the suppression of TNFalpha-induced MMP-9 production in acinar cells. METHODS:
      Two srIkappaBalpha complementary DNA (cDNA)-transfected acinar cell clones (ACMT
      6 and ACMT-7) and 1 empty vector-transfected cell clone (ACpRc-1) were
      established. After treatment of cell clones with TNFalpha, the expression of MMP
      9 was examined. In addition, the effect of TNFalpha on cell growth and the
      morphogenetic behavior of cell clones cultured on type IV collagen-coated dishes
      were examined. RESULTS: TNFalpha induced the production of MMP-9 in the ACpRc-1
      cell clone, but greatly suppressed MMP-9 production in ACMT-6 and ACMT-7 clones.
      No apparent cytotoxic effect of TNFalpha treatment was observed in these cell
      clones. When ACpRc-1 cells were seeded on type IV collagen-coated dishes in the
      presence of both TNFalpha and plasmin, type IV collagen interaction with the
      cells was lost and the cells entered apoptosis. However, even when ACMT-6 and
      ACMT-7 cells were cultured under the same culture conditions as those for ACpRc
      1, these cell clones attached to the substrate and grew consistently without
      showing apoptosis. Conclusion. These observations indicate that suppression of
      TNFalpha-induced MMP-9 production by the introduction of srIkappaBalpha cDNA
      corrected the aberrant in vitro morphogenesis of acinar cells grown on type IV
      collagen.

PMID- 10943867
TI  - SR proteins are autoantigens in patients with systemic lupus erythematosus.
      Importance of phosphoepitopes.
AB  - OBJECTIVE: To determine whether members of the highly phosphorylated SR protein
      family are autoantigens and, if so, to determine the frequency and molecular
      basis of antigen recognition. METHODS: Native human SR proteins were purified to
      homogeneity from HeLa cells, and an enzyme-linked immunosorbent assay (ELISA) was
      developed. Further studies employed immunoblotting of both phosphorylated and
      dephosphorylated SR proteins. RESULTS: Anti-SR protein reactivity was frequently
      detected in the sera of patients with systemic lupus erythematosus (SLE). Sera
      from 52% of the SLE patients in a group of patients with a variety of autoimmune
      and other disorders (n = 137) and from 50% of the SLE patients in a separate
      group (n = 102) were positive in an ELISA. In contrast, sera from patients with
      other disorders, such as rheumatoid arthritis and primary antiphospholipid
      syndrome, reacted infrequently. Reactivity with double-stranded DNA (dsDNA), used
      in the diagnosis of SLE, did not correlate with SR protein reactivity. Anti-SR
      autoantisera did not bind highly charged unphosphorylated peptides related to the
      SR domain, which is rich in arginine and phosphoserine residues. Surprisingly,
      many of the epitopes were influenced by the presence or absence of SR protein
      phosphorylation. In immunoblots, some patient sera lost reactivity upon SR
      protein dephosphorylation, while others significantly gained reactivity.
      CONCLUSION: We have identified a novel set of autoantigens in SLE, the SR protein
      family of non-small nuclear RNP pre-messenger RNA splicing factors. Anti-SR
      autoantibodies are distinct from those which bind dsDNA. The identification of
      this new set of autoantigens and the observation that the auto-epitope(s)
      involves posttranslational modification offer new possibilities for understanding
      autoimmunity and its development.

PMID- 10943868
TI  - Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse
      macrophages. Implications for the control of joint inflammation in gout.
AB  - OBJECTIVE: We have hypothesized that the process of monocyte to macrophage
      differentiation may alter the inflammatory response of mononuclear phagocytes to
      the uptake of monosodium urate monohydrate (MSU) crystals. METHODS: Eight mouse
      monocyte/macrophage cell lines were arranged in increasing order of
      differentiation, as judged by expression of the macrophage markers F4/80 and BM 8
      and by phagocytic capacity. Secretion of tumor necrosis factor alpha (TNFalpha)
      in response to MSU was measured by enzyme-linked immunosorbent assay. RESULTS:
      The panel of monocyte/macrophage cell lines revealed a close linkage between the
      state of differentiation and the capacity of the cells to ingest MSU crystals.
      TNFalpha production, however, was not linked to phagocytic ability. Peak TNFalpha
      levels were synthesized by cells at an intermediate state of differentiation (3.2
      14.1 ng/ml), whereas mature macrophages, which efficiently phagocytosed crystals,
      did not secrete TNFalpha. Mature cell lines produced TNFalpha when stimulated
      with zymosan (5.9-6.2 ng/ml), but this was abolished by coincubation with MSU
      crystals. Suppression of the zymosan response was not due to apoptosis or steric
      hindrance by MSU crystals. Culture supernatants from mature macrophages did not
      stimulate endothelial cell activation, in contrast to MSU-treated cells at an
      earlier stage of differentiation, which stimulated intercellular adhesion
      molecule 1 expression on sEND endothelioma cells through the release of TNFalpha
      (inhibited 80.6% by anti-TNFa). CONCLUSION: We demonstrated that phagocytosis and
      TNFalpha production are distinct events in the response of mononuclear phagocytes
      to urate crystals, and these events can be distinguished at the level of
      macrophage differentiation. The noninflammatory removal of urate crystals by
      mature macrophages defines a new pathway that may be important in controlling the
      development of acute gout in patients with hyperuricemia.

PMID- 10943869
TI  - Clinical and biologic effects of anti-interleukin-10 monoclonal antibody
      administration in systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the safety and clinical efficacy of administering an anti
      interleukin-10 (anti-IL-10) monoclonal antibody (mAb) to systemic lupus
      erythematosus (SLE) patients with active and steroid-dependent disease. In
      addition, we sought to assess the effects of in vivo IL-10 neutralization on
      biologic markers of SLE. METHODS: Treatment consisted of 20 mg/day intravenous
      administration of an anti-IL-10 murine mAb (B-N10) for 21 consecutive days, with
      a followup period of 6 months. Six patients were studied. RESULTS: Treatment was
      safe and well tolerated. All patients developed antibodies against B-N10.
      Cutaneous lesions and joint symptoms improved in all patients beginning during B
      N10 administration and continuing to month 6. The SLE Disease Activity Index
      decreased from a mean +/- SEM of 8.83+/-0.91 on day 1 to 3.67+/-0.67 on day 21 (P
      = 0.001), 1.50+/-0.84 at month 2, and 1.33+/-0.80 at month 6 (P<0.001). At the
      end of followup, the disease was clinically inactive in 5 of the 6 patients.
      Prednisone administration was decreased from a mean +/- SEM of 27.9+/-5.7 mg/day
      on day 1 to 9.6+/-2.0 mg/day at month 6 (P<0.005). Activity of immune and
      endothelial cells rapidly decreased, as assessed by the early evolution of
      several biologic markers. CONCLUSION: This is the first report of IL-10
      antagonist administration to humans. The study shows the involvement of IL-10 in
      the pathogenesis of SLE, and indicates that the use of IL-10 antagonists may be
      beneficial in the management of refractory SLE.

PMID- 10943870
TI  - Damage in systemic lupus erythematosus and its association with corticosteroids.
AB  - OBJECTIVE: To evaluate the association between corticosteroid use and organ
      damage in patients with systemic lupus erythematosus (SLE). METHODS: The
      occurrence and date of organ damage, as measured by the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage
      Index, were determined for 539 patients enrolled in the Hopkins Lupus Cohort
      Study. The risk of damage associated with the cumulative prednisone dose, high
      dose prednisone (> or =60 mg/day for > or =2 months), and pulse
      methylprednisolone (1,000 mg intravenously for 1-3 days) was estimated using Cox
      proportional hazards regression analyses, controlling for age, race, and sex.
      Risk estimates for the cumulative prednisone dose were based on a reference dose
      of 36.5 gm (e.g., 10 mg of prednisone daily for 10 years [or equivalent]).
      RESULTS: The cumulative prednisone dose was significantly associated with the
      development of osteoporotic fractures (relative risk [RR] 2.5, 95% confidence
      interval [95% CI] 1.7, 3.7), symptomatic coronary artery disease (RR 1.7, 95% CI
      1.1, 2.5), and cataracts (RR 1.9, 95% CI 1.4, 2.5). Each intravenous pulse was
      associated with a small increase in the risk of osteoporotic fractures (RR 1.3,
      95% CI 1.0, 1.8); however, this result failed to reach statistical significance
      (P = 0.07). Each 2-month exposure to high-dose prednisone was associated with a
      1.2-fold increase in the risk of both avascular necrosis (95% CI 1.1, 1.4) and
      stroke (95% CI 1.0, 1.5). CONCLUSION: SLE patients receiving long-term prednisone
      therapy were at significant risk of morbidity due to permanent organ damage.
      Additional research is required to determine the relative contributions of SLE
      disease activity and corticosteroids to the pathogenesis of specific types of
      organ damage. Furthermore, new steroid-sparing therapies are needed in order to
      treat disease activity and minimize cumulative and high-dose prednisone exposure.

PMID- 10943871
TI  - Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of
      treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids
      compared with sulfasalazine alone.
AB  - OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and
      corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA)
      can produce a significant improvement in outcome compared with standard
      monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients
      presenting with new, untreated RA of less than 12 months' duration who fulfilled
      criteria for poor long-term outcome were randomized to receive either combination
      therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were
      remission and American College of Rheumatology (ACR) criteria for 20% improvement
      at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR
      criteria for 20% improvement were not significantly different between the two
      groups (combination 58% versus SSZ 45%), and similar numbers of patients had
      persisting clinical remission (approximately 10% both groups). During the first 3
      months, there were significantly greater reductions in parameters of disease
      activity in the combination group. By 24 weeks, the swollen and tender joint
      counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen
      significantly in both groups, with a greater improvement in the swollen and
      tender joint count in the combination group. At 48 weeks, the radiographic damage
      score had increased by a median of 1 (range 0-42.5) in the combination group and
      1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant
      differences in the scores for the right hand). There were significantly fewer
      withdrawals due to lack of efficacy in the combination group than in the SSZ
      group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose
      reduction was needed in 22.5% because of hypertension and in 22.5% because of
      elevated creatinine levels. Over 48 weeks, serum creatinine increased in both
      groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA
      patients, "aggressive" combination therapy led to more rapid disease suppression
      but did not result in significantly better ACR response or remission rates. This
      suggests that in poor-prognosis disease, an approach based on identifying
      patients with poor treatment responses before extra therapy is added ("step-up"
      approach) may be more appropriate than the use of combination therapy in all
      patients from the outset.

PMID- 10943872
TI  - Modulation of inflammation and metalloproteinase expression in synovial tissue by
      leflunomide and methotrexate in patients with active rheumatoid arthritis.
      Findings in a prospective, randomized, double-blind, parallel-design clinical
      trial in thirty-nine patients at two centers.
AB  - OBJECTIVE: Leflunomide and methotrexate have proven to be efficacious in reducing
      joint inflammation and slowing destruction in clinical trials of patients with
      rheumatoid arthritis (RA). This study was conducted to provide more insight into
      the mechanism of action of these agents in synovial tissue. METHODS: In a 2
      center, prospective, randomized, double-blind clinical trial, we compared
      leflunomide (20 mg/day, after a 3-day 100 mg/day loading dose) and methotrexate
      (increased stepwise to 15 mg/week) treatment in patients with active RA. Paired
      synovial tissue biopsy samples were obtained by knee arthroscopy at baseline and
      after 4 months of treatment. Frozen synovial tissue sections were stained for
      macrophages (CD68), T cells (CD3), adhesion molecules (intercellular adhesion
      molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]), cytokines
      (tumor necrosis factor alpha, interleukin-1beta [IL-1beta]), matrix
      metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinases 1 (TIMP
      1). RESULTS: Paired synovial tissue sections were available in 35 patients (16
      taking leflunomide, 19 taking methotrexate). Both drugs displayed equal clinical
      efficacy, with 8 leflunomide-treated patients (50%) and 10 methotrexate-treated
      patients (53%) fulfilling the American College of Rheumatology 20% response
      criteria. Both compounds showed similar effects on synovial tissue: reduced
      numbers of macrophages and reduced ICAM-1 and VCAM-1 expression were noted after
      4 months of treatment. Both leflunomide- and methotrexate-treated patients
      exhibited a decreased MMP-1:TIMP-1 ratio in the synovial tissue. In the subset of
      patients fulfilling the 20% response criteria of the American College of
      Rheumatology, a more pronounced reduction in the expression of ICAM-1, VCAM-1, IL
      1beta, and MMP-1 was found compared with the nonresponders. CONCLUSION:
      Leflunomide and methotrexate are clinically efficacious drugs that interfere with
      mechanisms involved in joint inflammation and destruction of joint integrity.

PMID- 10943873
TI  - The prognostic value of anti-cyclic citrullinated peptide antibody in patients
      with recent-onset rheumatoid arthritis.
AB  - OBJECTIVE: To study the predictive value of anticyclic citrullinated peptide
      antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA).
      METHODS: Outcome in terms of physical disability (Health Assessment
      Questionnaire) and radiologic damage (modified Sharp method) over 3-year and 6
      year periods was determined in an inception cohort of 273 RA patients who had had
      disease symptoms for <1 year at study entry. Anti-CCP titers were determined at
      baseline and considered positive as recently described. Their prognostic value
      was studied by means of multiple regression analysis, in which anti-CCP
      positivity, sex, age at study entry, IgM rheumatoid factor (IgM-RF) status,
      Disease Activity Score (DAS), HLA-DR4 status, and (in a separate group of
      patients) shared epitope status were used as independent variables, and
      radiologic damage and functional disability as dependent variables. RESULTS:
      Patients with anti-CCP had developed significantly more severe radiologic damage
      after 6 years of followup. In multiple regression analysis, radiologic damage
      after 6 years followup was significantly predicted by IgM-RF status, radiologic
      score at entry, and anti-CCP status. Functional disability was significantly
      predicted by sex, age at entry, IgM-RF status, and DAS. CONCLUSION: Our data show
      that in almost 70% of RA patients, anti-CCP antibody is present at the early
      stages of disease. Anti-CCP-positive patients developed significantly more severe
      radiologic damage than patients who were anti-CCP negative, although in multiple
      regression analysis the additional predictive value was rather moderate.

PMID- 10943874
TI  - Use of methotrexate and glucocorticoids in the treatment of Wegener's
      granulomatosis. Long-term renal outcome in patients with glomerulonephritis.
AB  - OBJECTIVE: To determine the long-term renal outcome in patients with Wegener's
      granulomatosis (WG) and active glomerulonephritis who were treated with
      methotrexate (MTX) and glucocorticoids. METHODS: An open-label, prospective
      standardized trial using weekly low-dose MTX and glucocorticoids for the
      treatment of WG was performed. Forty-two patients were enrolled into the study,
      of whom 21 had active glomerulonephritis as a disease manifestation. The mean
      pretreatment level of serum creatinine in the patients with glomerulonephritis
      was 1.4 mg/dl. The extent of renal function in these patients at the time of
      their last followup was subsequently examined. RESULTS: Overall, 20 of 21
      patients achieved renal remission. At 1 month and 6 months following study entry,
      the serum creatinine level in all patients either remained stable or improved.
      The 20 patients have now been followed up for a median time of 76 months (range
      20-108 months). Only 2 patients have had a rise of >0.2 mg/dl in their creatinine
      level from the time of enrollment to the most recent followup examination. Of the
      remaining 18 patients, 12 have had stable renal function and 6 have had
      improvement in their creatinine levels by more than 0.2 mg/dl. CONCLUSION: In
      this study, the use of MTX and prednisone as initial therapy for patients with WG
      related glomerulonephritis and a normal or near-normal level of serum creatinine
      was not associated with a long-term decline in renal function.

PMID- 10943875
TI  - Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in
      patients with Wegner's granulomatosis undergoing immunosuppressive therapy.
AB  - OBJECTIVE: To assess the incremental cost-effectiveness of 3 Pneumocystis carinii
      pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis
      (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2)
      trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is
      discontinued if patients experience an adverse drug reaction (ADR); and 3)
      TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized
      pentamidine (300 mg) if patients experience an ADR. METHODS: A Markov state
      transition model was developed to follow a hypothetical cohort of WG patients
      over their lifetimes starting from the time of initial exposure to the
      immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy,
      quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and
      incremental cost-effectiveness was estimated based on data obtained from a
      literature review. Direct medical costs were examined from a societal
      perspective, and costs and benefits were discounted at 3% annually. RESULTS: No
      prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years
      (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone
      increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The
      addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61
      QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by
      pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per
      QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis
      strategies dominated the no prophylaxis strategy until the incidence of PCP fell
      below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for
      patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared
      with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%.
      CONCLUSION: Prophylaxis using TMP/SMX alone increased life expectancy and reduced
      cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX
      with monthly aerosolized pentamidine in cases of ADR further increased life
      expectancy, although at an increased cost.

PMID- 10943876
TI  - Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in
      children with extended oligoarticular or systemic arthritis.
AB  - OBJECTIVE: Juvenile idiopathic arthritis (JIA) can persist through adolescence
      and adulthood, resulting in significant disability. The use of low-dose oral
      methotrexate (MTX) for persistent polyarthritis has been shown to be effective by
      the USA/USSR collaborative study group. However, 2 of the most disabling
      subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in
      that study. The present study was therefore conducted to investigate the efficacy
      of MTX in these 2 subgroups. METHODS: Patients under the age of 16 years who
      fulfilled the International League of Associations for Rheumatology criteria for
      systemic or extended oligoarticular arthritis were eligible for this multicenter,
      double-blind, placebo-controlled crossover trial. Forty-five patients with
      systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage
      of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2
      months. Core outcome variables were considered as primary measures, giving a
      final score of "improved" or "not improved." Secondary measures included scores
      of systemic features and biochemical laboratory measures. Assessment of function
      was not included since there were no validated functional measures at the start
      of this trial in 1991. RESULTS: In the extended oligoarticular arthritis group,
      MTX treatment produced significant improvement in 3 of 5 core variables
      (erythrocyte sedimentation rate, physician's global assessment of disease
      activity, and parent's global assessment of disease activity). By the primary
      improvement criteria, there was significant overall improvement during MTX
      treatment. In the systemic arthritis group, only 2 of 5 core variables were
      significantly improved (physician's and parent's global assessment of disease
      activity). Systemic features were not part of the core variables, but the
      systemic feature score was not significantly different between MTX and placebo
      treatment. There was no significant overall improvement in this group during MTX
      treatment. However, no significant interaction between disease subgroup and
      treatment effect was demonstrated. When the data from both disease subgroups were
      combined, there was significant clinical improvement during MTX treatment (P =
      0.006). CONCLUSION: MTX 15-20 mg/m2 given orally once a week was found to be an
      effective treatment for both extended oligoarticular and systemic JIA in this
      shortterm trial. Long-term efficacy needs to be addressed in future studies.

PMID- 10943877
TI  - Long-term outcome and prognosis in oligoarticular-onset juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To describe the long-term outcome and determine predictors of severity
      among patients with oligoarticular-onset juvenile idiopathic arthritis (JIA).
      METHODS: In a longitudinal study, 207 patients with oligoarticular-onset JIA who
      were referred between 1988 and 1998 were evaluated. At disease onset, selected
      clinical and laboratory data were collected as independent variables. A
      polyarticular disease course, joint erosion, uveitis, and remission were assessed
      as dependent variables. Longitudinal analyses were performed with the Kaplan
      Meier method, and multivariate analysis with the Cox model. RESULTS: After 6
      years of followup, the probability of a polyarticular course of disease was 50%,
      joint erosion was 35%, uveitis was 30%, and remission was 23% in these patients.
      Joint erosion was strongly associated with a polyarticular course. A high
      erythrocyte sedimentation rate (ESR) as well as involvement of more than 1 joint
      or involvement of an upper limb at disease onset were predictors of disease
      extension. A high ESR was also a strong predictor of a destructive course, and a
      family history of psoriasis was predictive of uveitis occurrence. No predictive
      factor for remission could be identified. CONCLUSION: Oligoarticular-onset JIA is
      a severe disease with frequent complications. Factors predictive of severity in
      oligoarticular-onset JIA were identified. This could allow early identification
      of high-risk patient subgroups, warranting a more aggressive therapeutic
      approach.

PMID- 10943878
TI  - Magnetic resonance imaging detection of occult skin and subcutaneous
      abnormalities in juvenile dermatomyositis. Implications for diagnosis and
      therapy.
AB  - OBJECTIVE: To assess the utility of magnetic resonance imaging (MRI) of skin,
      subcutaneous tissue, and fascia in evaluating disease activity in juvenile
      dermatomyositis (DM). METHODS: Short tau inversion recovery (STIR) MRI of the
      proximal thighs and buttocks, cutaneous assessment, and other measures of disease
      activity were prospectively obtained in 26 children meeting criteria for probable
      or definite juvenile DM. Also undergoing STIR MRI assessment were 8 subjects who
      were being evaluated for muscle disorders and who were not diagnosed as having
      juvenile DM. RESULTS: Skin, subcutaneous, or fascial edema of the thighs and
      buttocks were seen on STIR MRI in up to 85% of juvenile DM patients at baseline
      evaluation compared with no more than 38% of the comparison group without
      juvenile DM. In juvenile DM, STIR MRI skin and subcutaneous edema scores
      correlated (r(s) = 0.51, P = 0.008), as did fascial and muscle edema scores (r(s)
      = 0.58, P = 0.002). Skin global disease activity scores correlated with MRI skin
      edema scores (r(s) = 0.41, P = 0.04), and serum aldolase levels correlated with
      both MRI skin and subcutaneous edema scores (r = 0.44 and 0.40, P = 0.03 and 0.05
      respectively). The extent and severity of STIR MRI changes in the skin,
      subcutaneous tissue, and fascia were not predicted by most other measures of
      juvenile DM disease activity. Five juvenile DM patients with thigh MRI
      subcutaneous edema developed clinically apparent calcinosis at the same location
      within 9 months. CONCLUSION: Edema or inflammation in the skin, subcutaneous
      tissue, and fascia, found on STIR MRI, is common in juvenile DM patients and is
      often undetected by standard assessments. These MRI changes can precede the
      development of calcinosis. STIR MRI may be a useful adjunct for assessing disease
      activity and guiding the treatment of juvenile DM.

PMID- 10943879
TI  - The association between varus-valgus alignment and patellofemoral osteoarthritis.
AB  - OBJECTIVE: Little is known about risk factors for patellofemoral (PF)
      osteoarthritis (OA). The lateral vector at the PF joint increases the likelihood
      of lateral PF versus medial PF pathology. Both valgus and varus malalignments
      affect forces at the PF joint and may predispose to PF OA. We examined whether
      lateral PF OA is more common than medial PF OA, whether valgus malalignment is
      more frequent in lateral PF OA than in medial PF OA, and whether knees with PF OA
      are more often valgus than knees with isolated tibiofemoral (TF) OA. METHODS: In
      292 knee OA patients, we obtained semiflexed, fluoroscopy-confirmed radiographs
      of the TF joint and weight-bearing, 30 degrees flexion, axial views of the PF
      joint. Varus-valgus alignment (the angle formed by the intersection of the
      mechanical axes of the femur and tibia) was measured on a full-limb radiograph.
      RESULTS: Lateral PF OA was more common than medial PF OA (P<0.0001). Forty-three
      of 75 knees with lateral PF OA had valgus malalignment compared with only 5 of 21
      patients with medial PF OA (P = 0.0066). Conversely, varus malalignment was more
      likely in the medial PF OA group. Knees with isolated PF OA were more likely to
      have valgus malalignment than those with isolated TF OA (P = 0.0002), as were
      knees with mixed PF-TF OA (P = 0.0006). CONCLUSION: Varus-valgus alignment may
      influence the risk of PF OA and, in particular, which compartment is affected.

PMID- 10943880
TI  - Evaluating the predictive value of osteoarthritis diagnoses in an administrative
      database.
AB  - OBJECTIVE: To assess the positive and negative predictive values of
      osteoarthritis (OA) diagnoses contained in an administrative database. METHODS:
      We identified all members (> or =18 years of age) of a Massachusetts health
      maintenance organization with documentation of at least one health care encounter
      associated with an OA diagnosis during the period 1994-1996. From this
      population, we randomly selected 350 subjects. In addition, we randomly selected
      250 enrollees (proportionally by the age and sex of the 350 subjects) who did not
      have a health care encounter associated with an OA diagnosis. Trained nurse
      reviewers abstracted OA-related clinical, laboratory, and radiologic data from
      the medical records of both study groups (all but 1 chart was available for
      review). Pairs of physician reviewers evaluated the abstracted information for
      both groups of subjects and rated the evidence for the presence of OA according
      to 3 levels: definite, possible, and unlikely. RESULTS: Among the group of
      patients with an administrative diagnosis of OA, 215 (62%) were rated as having
      definite OA, 36 (10%) possible OA, and 98 (28%) unlikely OA, according to
      information contained in the medical record. The positive predictive value of an
      OA diagnosis was 62%. In those without an administrative OA diagnosis, 44 (18%)
      were assigned a rating of definite OA. The negative predictive value of the
      absence of an administrative OA diagnosis was 78%. CONCLUSION: Use of
      administrative data in epidemiologic and health services research on OA may lead
      to both case misclassification and under ascertainment.

PMID- 10943881
TI  - Increased alpha2-adrenergic constriction of isolated arterioles in diffuse
      scleroderma.
AB  - OBJECTIVE: Vasospasm and ischemic organ injury are important in the pathogenesis
      of systemic sclerosis (SSc; scleroderma). The present study was performed to
      determine whether SSc arterioles have an intrinsic disturbance in vasoconstrictor
      activity. METHODS: Skin biopsy samples were obtained from the upper arm of 11
      patients with diffuse SSc (clinically uninvolved skin) and 8 age- and sex-matched
      control subjects. Dermal arterioles were dissected from the biopsy sample and
      mounted in a myograph for continuous monitoring of arteriolar diameter. The
      resting internal diameter of control and SSc arterioles was similar (mean +/- SEM
      164+/-15 micro and 166+/-18micro, respectively). RESULTS: Dermal arterioles
      displayed no spontaneous constrictor activity in the absence of stimulation.
      Vasoconstriction in response to KCI, a receptor-independent activator of smooth
      muscle, or to phenylephrine, a selective alpha1-adrenergic receptor (alpha1-AR)
      agonist, was similar in control and SSc arterioles. However, constrictor
      responses to UK 14,304, a selective alpha2-AR agonist, were increased in SSc
      compared with control arterioles (maximal constriction responses of 25+/-5% and
      67+/-4% [mean +/- SEM] in control and SSc arterioles, respectively; P =
      0.000014). Mechanical denudation of the endothelium did not alter reactivity to
      alpha2-AR activation, indicating that the enhanced constriction in SSc was not
      mediated by changes in endothelial dilator activity. Indeed, in arterioles
      constricted with phenylephrine, the endothelial stimuli acetylcholine or
      bradykinin evoked endothelium-dependent relaxation that was similar in control
      and SSc arterioles. CONCLUSIONS: Vascular smooth muscle in SSc arterioles
      displayed a selective increase in alpha2-AR reactivity. The endothelial dilator
      function appeared normal. Altered activity of smooth muscle alpha2-ARs may
      contribute to the vasospastic activity that is a prominent feature of the SSc
      disease process.

PMID- 10943882
TI  - Thrombosis in patients with connective tissue diseases treated with specific
      cyclooxygenase 2 inhibitors. A report of four cases.
AB  - Specific inhibitors of cyclooxygenase 2 (COX-2) have been approved for the
      treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal anti
      inflammatory drugs, specific COX-2 inhibitors do not inhibit platelet activation.
      However, these agents significantly reduce systemic production of prostacyclin.
      As a result, theoretical concerns have been raised that specific COX-2 inhibitors
      could shift the hemostatic balance toward a prothrombotic state. Patients with
      connective tissue diseases (CTD), who may be predisposed to vasculopathy and
      thrombosis, often have arthritis or pain syndromes requiring treatment with
      antiinflammatory agents. Herein we describe 4 patients with CTD who developed
      ischemic complications after receiving celecoxib. All patients had a history of
      Raynaud's phenomenon, as well as elevated anticardiolipin antibodies, lupus
      anticoagulant, or a history compatible with antiphospholipid syndrome. It was
      possible to measure a urinary metabolite of thromboxane A2 in 2 of the patients
      as an indicator of in vivo platelet activation, and this was markedly elevated in
      both. In addition, the patients had evidence of ongoing inflammation as indicated
      by elevated erythrocyte sedimentation rate, hypocomplementemia, and/or elevated
      levels of anti-DNA antibodies. The findings in these 4 patients suggest that COX
      2 inhibitor-treated patients with diseases that predispose to thrombosis should
      be monitored carefully for this complication.

PMID- 10943883
TI  - Churg-Strauss syndrome: localization of eosinophil major basic protein in damaged
      tissues.

PMID- 10943884
TI  - Protein-losing gastroenteropathy in system lupus erythematosus: diagnosis with
      99mTc--human serum albumin scintigraphy.

PMID- 10943885
TI  - Anticitrulline antibody assay specificity for rheumatoid arthritis: comment on
      the article by Schellekens et al.

PMID- 10943886
TI  - Reponse to methotrexate and reduced mortality in patients with rheumatoid
      arthritis: comment on the article by Krause et al.

PMID- 10943887
TI  - The role of nuclear medicine in the evaluation of neuropsychiatric systemic lupus
      erythematosus: comment on the article by Sibbitt et al.

PMID- 10943888
TI  - Emerging features of mRNA decay in bacteria.
AB  - The problem of mRNA decay in E. coli has recently seen exciting progress, with
      the discoveries that key degradation enzymes are associated together in a high
      molecular weight degradosome and that polyadenylation promotes decay. Recent
      advances make it clear that mRNA decay in bacteria is far more interesting
      enzymatically than might have been predicted. In-depth study of specific mRNAs
      has revealed multiple pathways for degradation. Which pathway a given mRNA
      follows appears to depend in large part on the location of the initiating
      endonucleolytic cleavage within the mRNA. During the steps of mRNA decay, stable
      RNA structures pose formidable barriers to the 3' --> 5' exonucleases. However,
      polyadenylation is now emerging as a process that plays an important role in
      maintaining the momentum of exonucleolytic degradation by adding single-stranded
      extensions to the 3' ends of mRNAs and their decay intermediates, thereby
      facilitating further exonuclease digestion.

PMID- 10943889
TI  - The crystal structure of yeast phenylalanine tRNA at 1.93 A resolution: a classic
      structure revisited.
AB  - The crystal structure of the monoclinic form of yeast phenylalanine tRNA has been
      redetermined at a resolution of 1.93 A. The structure of yeast tRNAphe described
      here is more accurate than its predecessors not only because it incorporates
      higher resolution data, but also because it has been refined using techniques
      that had not been developed when its predecessors were determined more than 20
      years ago. The 1.93 A resolution version of this structure differs interestingly
      from its predecessors in its details. In loop regions particularly, the backbone
      torsion angles in the new structure are not the same as those reported earlier.
      Several new divalent cation binding sites have been identified, and the water
      structure that has emerged is also different.

PMID- 10943890
TI  - Dominant negative mutants of the yeast splicing factor Prp2 map to a putative
      cleft region in the helicase domain of DExD/H-box proteins.
AB  - The Prp2 protein of Saccharomyces cerevisiae is an RNA-dependent ATPase required
      before the first transesterification reaction in pre-mRNA splicing. Prp2 binds to
      the spliceosome in the absence of ATP and is released following ATP hydrolysis.
      We determined what regions in Prp2 are essential for release from the spliceosome
      by analyzing dominant negative mutants in vivo and in vitro. We made mutations in
      conserved motif II (DExH) and motif VI (QRxGR) of the helicase (H) domain.
      Mutations that inactivated PRP2 had a dominant negative phenotype when
      overexpressed in vivo. To test whether mutations outside of the H domain could
      confer a dominant negative phenotype, we mutagenized a GAL1-PRP2 construct and
      screened for mutants unable to grow on galactose-containing media. Five dominant
      negative mutants were characterized; three mapped within the H domain and two
      mapped downstream of motif VI, indicating that an extended helicase domain is
      required for release of Prp2 from the spliceosome. Most mutants stalled in the
      spliceosome in vitro. However, not all mutants that were dominant negative in
      vivo were dominant negative in vitro, indicating that multiple mechanisms may
      cause a dominant negative phenotype. Structural modeling of the H domain of Prp2
      suggests that mutants map to a cleft region found in helicases of known
      structure.

PMID- 10943891
TI  - Identification of a U2/U6 helix la mutant that influences 3' splice site
      selection during nuclear pre-mRNA splicing.
AB  - Base substitutions in U2/U6 helix I, a conserved base-pairing interaction between
      the U6 and U2 snRNAs, have previously been found to specifically block the second
      catalytic step of nuclear pre-mRNA splicing. To further assess the role of U2/U6
      helix I in the second catalytic step, we have screened mutations in U2/U6 helix I
      to identify those that influence 3' splice site selection using a derivative of
      the yeast actin pre-mRNA. In these derivatives, the spacing between the branch
      site adenosine and 3' splice site has been reduced from 43 to 12 nt and this
      results in enhanced splicing of mutants in the conserved 3' terminal intron
      residue. In this context, mutation of the conserved 3' intron terminal G to a C
      also results in the partial activation of a nearby cryptic 3' splice site with U
      as the 3' terminal intron nucleotide. Using this highly sensitive mutant
      substrate, we have identified a mutation in the U6 snRNA (U57A) that
      significantly increases the selection of the cryptic 3' splice site over the
      normal 3' splice site and augments its utilization relative to that observed with
      the wild-type U2 or U6 snRNAs. In a previous study, we found that the same U6
      mutation suppressed the effects of an A-to-G branch site mutation in an allele
      specific fashion. The ability of U6-U57 mutants to influence the fidelity of both
      branch site and 3' splice site recognition suggests that this nucleotide may
      participate in the formation of the active site(s) of the spliceosome.

PMID- 10943892
TI  - tRNA determinants for transcription antitermination of the Bacillus subtilis tyrS
      gene.
AB  - Transcriptional regulation of the T box family of aminoacyl-tRNA synthetase and
      amino acid biosynthesis genes in Gram-positive bacteria is mediated by a
      conserved transcription antitermination system, in which readthrough of a
      termination site in the leader region of the mRNA is directed by a specific
      interaction with the cognate uncharged tRNA. The specificity of this interaction
      is determined in part by pairing of the anticodon of the tRNA with a "specifier
      sequence" in the leader, a codon representing the appropriate amino acid, as well
      as by pairing of the acceptor end of the tRNA with an unpaired region of the
      antiterminator. Previous studies have indicated that although these interactions
      are necessary for antitermination, they are unlikely to be sufficient. In the
      current study, the effect of multiple mutations in tRNA(Tyr) on readthrough of
      the tyrS leader region terminator, independent of other tRNA functions, was
      assessed using a system for in vivo expression of pools of tRNA variants; this
      system may be generally useful for in vivo expression of RNAs with defined end
      points. Although alterations in helical regions of tRNA(Tyr) that did not perturb
      base pairing were generally permitted, substitutions affecting conserved features
      of tRNAs were not. The long variable arm of tRNA(Tyr) could be replaced by either
      a short variable arm or a long insertion of a stable stem-loop structure. These
      results indicate that the tRNA-leader RNA interaction is highly constrained, and
      is likely to involve recognition of the overall tertiary structure of the tRNA.

PMID- 10943893
TI  - Substrate recognition by a eukaryotic RNase III: the double-stranded RNA-binding
      domain of Rnt1p selectively binds RNA containing a 5'-AGNN-3' tetraloop.
AB  - Rnt1p is an RNase III homolog from budding yeast, required for processing snRNAs,
      snoRNAs, and rRNA. Numerous Rnt1p RNA substrates share potential to form a duplex
      structure with a terminal four-base loop with the sequence AGNN. Using a
      synthetic RNA modeled after the 25S rRNA 3' ETS cleavage site we find that the
      AGNN loop is an important determinant of substrate selectivity. When this loop
      sequence is altered, the rate of Rnt1p cleavage is reduced. The reduction in
      cleavage rate can be attributed to reduced binding of the mutant substrate as
      measured by a gel-shift assay. Deletion of the nonconserved N-terminal domain of
      Rnt1p does not affect cleavage site choice or the ability of the enzyme to
      distinguish substrates that contain the AGNN loop, indicating that this region is
      not required for selective cleavage. Strikingly, a recombinant fragment of Rnt1p
      containing little more than the dsRBD is able to discriminate between wild-type
      and mutant loop sequences in a binding assay. We propose that a major determinant
      of AGNN loop recognition by Rnt1p is present in its dsRBD.

PMID- 10943894
TI  - Mutational study reveals that tertiary interactions are conserved in ribosomal
      frameshifting pseudoknots of two luteoviruses.
AB  - Expression of the putative replicase of potato leafroll virus (PLRV) is regulated
      by -1 ribosomal frameshifting in which a primary viral transcript has two
      overlapping open reading frames (ORFs). A region of 39 nt at the junction of the
      two ORFs is essential for frameshifting to occur. It has been shown to harbor two
      signals, one active on the level of the primary structure, termed the slippery
      sequence, and one component that forms a secondary or tertiary level structure,
      described as either a pseudoknot or a stem-loop motif. We have performed
      extensive site-directed mutagenesis of the frameshifting region and analyzed
      individual mutants for their ability to promote -1 frameshifting in vitro.
      Detailed comparison of our results with analogous mutants in the frameshifting
      region of the evolutionarily related beet western yellow virus, for which a
      crystal structure is available, unequivocally argues for the pseudoknot to be the
      structural motif necessary for the frameshifting function in PLRV transcripts.
      Mutations in PLRV that affect putative pseudoknot-specific tertiary-base
      interactions drastically affect frameshifting activity. In addition, a specific
      deletion mutant was identified that displayed PLRV wild-type frameshifting
      activity with only 22 nt available for pseudoknot formation.

PMID- 10943895
TI  - Alterations in the peptidyltransferase and decoding domains of ribosomal RNA
      suppress mutations in the elongation factor G gene.
AB  - The translocation stage of protein synthesis is a highly conserved process in all
      cells. Although the components necessary for translocation have been delineated,
      the mechanism of this activity has not been well defined. Ribosome movement on
      template mRNA must allow for displacement of tRNA-mRNA complexes from the
      ribosomal A to P sites and P to E sites, while ensuring rigid maintenance of the
      correct reading frame. In Escherichia coli, translocation of the ribosome is
      promoted by elongation factor G (EF-G). To examine the role of EF-G and rRNA in
      translocation we have characterized mutations in rRNA genes that can suppress a
      temperature-sensitive (ts) allele of fusA, the gene in E. coli that encodes EF-G.
      This analysis was performed using the ts E. coli strain PEM100, which contains a
      point mutation within fusA. The ts phenotype of PEM100 can be suppressed by
      either of two mutations in the decoding region of the 16S rRNA when present in
      combination with a mutation at position 2058 in the peptidyltransferase domain of
      the 23S rRNA. Communication between these ribosomal domains is essential for
      coordinating the events of the elongation cycle. We propose a model in which EF-G
      promotes translocation by modulating this communication, thereby increasing the
      efficiency of this fundamental process.

PMID- 10943897
TI  - RNase II removes the oligo(A) tails that destabilize the rpsO mRNA of Escherichia
      coli.
AB  - Polyadenylation controls mRNA stability in procaryotes, eucaryotes, and
      organelles. In bacteria, oligo(A) tails synthesized by poly(A) polymerase I are
      the targets of the 3'-to-5' exoribonucleases: polynucleotide phosphorylase and
      RNase II. Here we show that RNase II very efficiently removes the oligo(A) tails
      that can be used as binding sites by PNPase to start degradation of the rpsO
      mRNA. Both enzymes are impeded by the secondary structure of the transcription
      terminator at the 3' end of the mRNA. RNase II mostly generates tailless
      transcripts harboring 2 unpaired nt downstream of the transcription terminator
      hairpin, whereas PNPase releases molecules that exhibit a single-stranded stretch
      of 5-7 nt terminated by a tail of 3-5 As. The rpsO mRNAs whose oligo(A) tails
      have been removed by RNase II are more stable than oligoadenylated molecules that
      occur in strains deficient for RNase II. Moreover, the rpsO mRNA is stabilized
      when RNase II is overproduced. This modulation of mRNA stability by RNase II is
      only observed when poly(A) polymerase I is active. These in vivo data demonstrate
      that RNase II protects mRNAs ending by stable terminal hairpins, such as primary
      transcripts, from degradation by poly(A)-dependent ribonucleases.

PMID- 10943896
TI  - Mutations in helix 27 of the yeast Saccharomyces cerevisiae 18S rRNA affect the
      function of the decoding center of the ribosome.
AB  - A dynamic structural rearrangement in the phylogenetically conserved helix 27 of
      Escherichia coli 16S rRNA has been proposed to directly affect the accuracy of
      translational decoding by switching between "accurate" and "error-prone"
      conformations. To examine the function of helix 27 in eukaryotes, random and site
      specific mutations in helix 27 of the yeast Saccharomyces cerevisiae 18S rRNA
      have been characterized. Mutations at positions of yeast 18S rRNA corresponding
      to E. coli 886 (rdn8), 888 (rdn6), and 912 (rdn4) increased translational
      accuracy in vivo and in vitro, and caused a reduction in tRNA binding to the A
      site of mutant ribosomes. The double rdn4rdn6 mutation separated the killing and
      stop-codon readthrough effects of the aminoglycoside antibiotic, paromomycin,
      implicating a direct involvement of yeast helix 27 in accurate recognition of
      codons by tRNA or release factor eRF1. Although our data in yeast does not
      support a conformational switch model analogous to that proposed for helix 27 of
      E. coli 16S rRNA, it strongly suggests a functional conservation of this region
      in tRNA selection.

PMID- 10943898
TI  - Platinum-group elements: quantification in collected exhaust fumes and studies of
      catalyst surfaces.
AB  - Automotive catalytic converters, in which Pt, Pd and Rh (platinum-group elements;
      PGEs) are the active components for eliminating several noxious components from
      exhaust fumes, have become the main source of environmental urban pollution by
      PGEs. This work reports on the catalyst morphology through changes in catalyst
      surface by scanning electron microscopy/energy dispersive X-ray spectroscopy
      (SEM/EDX) and laser-induced breakdown spectrometry (LIBS) from fresh to aged
      catalytic converters. The distribution of these elements in the fresh catalysts
      analysed (Pt-Pd-Rh gasoline catalyst) is not uniform and occurs mainly in a
      longitudinal direction. This heterogeneity seems to be greater for Pt and Pd.
      PGEs released by the catalysts, fresh and aged 30,000 km, were studied in
      parallel. Whole raw exhaust fumes from four catalysts of three different types
      were also examined. Two of these were gasoline catalysts (Pt-Pd Rh and Pd-Rh) and
      the other two were diesel catalysts (Pt). Samples were collected following the
      91,441 EUDC driving cycle for light-duty vehicle testing. The results show that
      at 0 km the samples collected first have the highest content of particulate PGEs
      and although the general tendency is for the release to decrease with increasing
      number of samples taken, exceptions are frequent. At 30,000 km the released PGEs
      in gasoline and diesel catalysts decreased significantly. For fresh gasoline
      catalysts the mean of the total amount released was approximately 100, 250 and 50
      ng km(-1) for Pt, Pd and Rh, respectively. In diesel catalysts the Pt release
      varied in the range 400-800 ng km-1. After ageing the catalysts up to 30,000 km,
      the gasoline catalysts released amounts of Pt between 6 and 8 ng km(-1), Pd
      between 12 and 16 ng km(-1) and Rh between 3 and 12 ng km(-1). In diesel
      catalysts the Pt release varied in the range 108-150 ng km(-1). The soluble
      portion of PGEs in the HNO3 collector solution represented less than 5% of the
      total amount for fresh catalysts. For 30,000 km the total amount of soluble PGEs
      released was similar or slightly higher than for 0 km.

PMID- 10943899
TI  - Distribution of polychlorinated biphenyls in marine species from French Frigate
      Shoals, North Pacific Ocean.
AB  - Polychlorinated biphenyls (PCBs) were analyzed in: sediment; coral (Porites
      evermanni); fish (Stegastes fasciolatus, Neoniphon sammara, Acanthurus triostegus
      and Mulloidichthys vanicolensis); crab (Grapsus tenuicrustatus); lobster
      (Panulirus marginatus); and eel (Conger cinereus, Gymnothoraxflavimarginatus, G.
      undulatus and G. meleagris) samples collected from Tern Island and the
      corresponding reference samples from Disappearing Island. The two islands are
      part of French Frigate Shoals, a national wildlife refuge in the North Pacific
      Ocean. The dominant congeners 118, 138 and 153 represent 22-25, 32-34, 12-39, 37
      46 and 30-55% of the sum of PCBs in the coral, sediment, fish, crab and eel,
      respectively. In general, high trophic species such as eels were found to highly
      bioaccumulate PCBs. The total average PCB concentrations were as high as 96 and
      29 microg/g dry wt. in eels and damselfish, respectively, from Tern Island. The
      localized behavior and high bioaccumulation potential for PCBs suggest that
      damselfish are an excellent species for monitoring PCBs in small areas in the
      ocean. The high average concentrations of the sum of PCBs in different food chain
      levels suggest that pollution source(s) are around Tern Island and possibly
      around Disappearing Island. Aroclor 1254 and its analogs are suspected sources
      responsible for PCBs in the samples.

PMID- 10943900
TI  - Comparing in situ distribution coefficients and exchangeability of radiocaesium
      in freshwater sediments with laboratory predictions.
AB  - Two short-term (24 h) laboratory procedures, based on measurement of the affinity
      and capacity of the specific binding sites for radiocaesium on illitic clay
      minerals, are used to predict the in situ 137Cs distribution coefficients (KD) in
      two Dutch freshwater sediments. Differences in the measured amount of specific
      binding sites between the sediments are shown to be related to differences in the
      particle size and illite content. A procedure based on measurement of the
      combined parameter KD[NH4+] predicts the measured in situ 137Cs distribution in
      both sediments very well. This is remarkable because the in situ data are based
      on 137Cs/sediment contact times of > 1 year, while previous experiments have
      shown that increasing contact times between Cs+ and sediments decreases the short
      term exchangeability of caesium, as measured by extraction with a high ammonium
      concentration. The good predictions of the 37Cs solid/water distribution by short
      term ion-exchange experiments, therefore, indicate that more 137Cs in the
      sediments is exchangeable than is measured by the commonly used extraction with
      high ammonium concentrations.

PMID- 10943901
TI  - Metal levels in feathers of 12 species of seabirds from midway atoll in the
      northern Pacific Ocean.
AB  - Seabirds are excellent subjects for examination of heavy metals because they are
      long-lived, feed at different distances from land, and exhibit different trophic
      levels. In this paper we compare the levels of lead, cadmium, mercury arsenic,
      chromium, manganese, selenium, and tin in the feathers of birds nesting on Midway
      Atoll in the northern Pacific Ocean. We test the null hypothesis that there are
      no interspecific differences in the levels of metals in the feathers of the adult
      black-footed albatross (Diomedea nigripes), Laysan albatross (Diomedea
      immutabilis), red-footed booby (Sula sula), great frigatebird (Fregata minor),
      Bonin petrel (Pterodroma hypoleuca), Christmas shearwater (Puffinus nativitatis),
      red-tailed tropicbird (Phaethon rubricauda), wedge-tailed shearwater (Puffinus
      pacificus), brown noddy (Anous stolidus), sooty tern (Stema fuscata), grey-backed
      tern (Stema lunata), and white tern (Gygis alba), and young of some of these
      species. There were interspecific differences in the levels of all metals for
      adults. Christmas shearwater had the highest levels of lead, cadmium, selenium
      and manganese, but the second lowest levels of mercury. In general, metal levels
      were the lowest in the smallest species (white tern), but were not the highest in
      the largest species (black-footed albatross), except for manganese, arsenic and
      mercury. There was a high variance in metal levels among adults for some species,
      but not for others. White tern adults were variable for lead, while Christmas
      shearwaters were variable for lead and cadmium. Compared to the means for metals
      in other birds generally (after Burger, 1993), Christmas shearwaters had higher
      levels of lead, white terns, brown noddy, Christmas shearwater, frigatebirds and
      Laysan albatrosses had higher levels of cadmium, and bonin petrel, wedge-tailed
      shearwater, tropicbirds, frigatebirds, red-footed boobies, and both albatrosses
      had higher levels of mercury. Whereas the means for lead and cadmium were below
      the known effects levels, some individuals had levels high enough to cause
      adverse effects in the birds. The mean values for mercury in Bonin petrel, red
      tailed tropicbird, and black-footed albatross were higher than the levels known
      to cause adverse reproductive and behavioral effects.

PMID- 10943902
TI  - Concentrations of cadmium, lead and zinc in livestock feed and organs around a
      metal production centre in eastern Kazakhstan.
AB  - This paper presents results of analysis of animal feed and meat (cattle, horse
      and sheep) products from a metal processing region (Oskemen) in east Kazakhstan.
      Samples were collected from a range of districts of differing distances from the
      main source of anthropogenic pollution and with differing underlying metal
      containing geologies. Analyses for cadmium, lead and zinc revealed high
      concentrations in many feed and meat samples. Horse (an important food animal)
      samples had higher levels of contamination than cattle, which were higher than
      sheep. For example, mean cadmium concentrations in horse kidneys in one district
      were found to be 128 mg/kg and lead concentrations for liver 2.2 mg/kg. These,
      and other, results are generally higher than reported in many other studies in
      contaminated regions of eastern Europe and they can exceed State Maximal Allowed
      Concentrations by many times. As such levels of contamination pose a significant
      potential risk to human health, these results have formed the basis for
      subsequent research on levels of metal contamination in human tissues from
      affected populations.

PMID- 10943903
TI  - The incidence of polychlorinated biphenyl and organochlorine pesticide residues
      in the eggs of the cormorant (Phalacrocorax carbo sinensis): an evaluation of the
      situation in four Greek wetlands of international importance.
AB  - This study contributed to identifying the current levels of organochlorine
      pollutants in four Greek wetlands of international importance (the Evros and
      Axios Deltas, and Kerkini and Prespa Lakes), using the cormorant Phalacrocorax
      carbo sinensis as a suitable bioindicator in a region where such information is
      scarce. Residue levels of eight polychlorinated biphenyl (PCB) congeners and 13
      organochlorine pesticide (OC) compounds were measured in cormorant eggs. Most
      PCBs and OCs (except dieldrin and endrin) were found in at least some of the
      study areas. Median concentrations of five PCBs (IUPAC 8, 20, 52, 138, 180) and
      of six OCs (alpha-BHC, beta-BHC, lindane, heptachlor, 4,4'-DDE and 4,4'-DDT)
      differed significantly among the areas. The median totals of the PCBs were highly
      significant among the areas, being unexpectedly highest in Prespa Lake (68.43
      ppb), despite its remoteness, and lowest in Evros Delta samples (12.17 ppb).
      Aldrin that was found in samples from Evros, Axios and Prespa probably
      accumulated in wintering grounds. In all of the areas, the relative proportions
      of alpha-BHC and 2,4'-DDD were the highest of all OCs. Fingerprint and cluster
      analyses illustrated overall differences in the PCB patterns, being greatest
      between the deltas than between the lakes, but, inversely, for OCs the
      differences were smaller in the deltas. Differences were attributed to large
      variations in the cormorants' diet between areas and different regimes of
      pollutant management in the two types of wetland. Correlations of pollutants
      varied considerably among areas and they were more diverse in OCs. The sum of
      OCs/ sum of PCBs ratio indicates agrochemical pollution in all areas. An
      important finding was that levels of both pollutant groups were too low to have
      any biological implications on the cormorants and, additionally, suggest that
      they have a negligible impact on the environment of the wetlands studied.

PMID- 10943904
TI  - Persisting consequences of drug intake: towards a memory of addiction.
AB  - Long-term intake of a psychoactive drug alters brain signal transduction,
      emotional and motivational factors and behavioral parameters. Some effects that
      outlast long periods of abstinence are due to the long-term presence of the drug
      in the organism (tolerance, physical dependence). Withdrawal symptoms, as a
      consequence of physical dependence, can be protracted, i.e. they persist after
      long periods of drug deprivation (e.g. a desensitization of the production of
      cAMP). Further persisting effects include experience-based learning. At least
      three distinct processes can be differentiated: a memory of drug effects
      (reflected by a sensitization to drug effects etc.), a memory of drug use
      (reflected by controlled drug consumption), and a memory of addiction (reflected
      by a persisting loss of control over drug intake and correlating changes in
      striatal dopaminergic neurotransmission). The latter probably consists of two
      components: a general memory of loss of control and a specific memory of the
      addictive drug (general principles for the development of addiction, specific of
      the urge for the addictive drug).

PMID- 10943905
TI  - Granule cell proliferation and axon terminal degradation in the dentate gyrus of
      gerbils (Meriones unguiculatus) during maturation, adulthood and aging.
AB  - The objective of the present study was to examine both naturally occurring
      degrading events in axon terminals of the dentate gyrus and granule cell
      proliferation in the dentate gyrus of gerbils (Meriones unguiculatus) throughout
      postnatal life. For that purpose, (1) a selective silver staining technique was
      applied to analyze neuronal lysosome accumulation (LA), indicating synaptic
      degradation during development. LA was quantified by counting silver grains in
      the inner third and outer two thirds of the molecular layer, granular layer,
      subgranular layer and the hilus of the dentate gyrus. (2) Proliferation of
      granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine
      (BrdU). BrdU-labeled granule cell nuclei were identified in consecutive
      horizontal slices along the mid-septotemporal axis of the hippocampus and light
      microscopically quantified 4h after the BrdU-labeling. It was found (1) that in
      young animals LA significantly increased within all layers and reached adult
      levels after about 3 months. During subsequent development LA kept on this level
      throughout aging with highest values within the inner molecular layer. (2) There
      was a highly significant temporal gradient in granule cell proliferation with
      numbers of BrdU-labeled cells exponentially declining during juvenile life.
      Nevertheless, granule cell proliferation occurred throughout adult life and
      aging. The present results are discussed (1) with concepts of ongoing
      neuroplasticity and remodeling of neuronal networks in the developing and adult
      brain, and (2) with regard to pharmacologically induced neuromorphogenesis.

PMID- 10943906
TI  - Animal models of addiction: models for therapeutic strategies?
AB  - When having a continuous free choice in their home cages between water and
      alcohol- or drug-containing drinking solutions, rats first develop a controlled
      consumption of the psychotropic compound and, after several months, lose their
      control over drug taking. After a long period of abstinence, they reveal an
      excessive, compulsive drug intake. Adulteration of the drug-containing solutions
      reduces the doses taken by controlled consumers, but not those of the excessive
      drinkers, they can therefore be regarded as addicted. These animals show a pre
      intake motor restlessness that may be related to craving. In two studies with
      putative anti-craving agents (the dopamine D2 receptor agonist lisuride and the
      D2 receptor antagonist flupentixol) we treated alcohol-addicted and non-addicted
      rats and observed the effects on alcohol taking, alcohol seeking and brain
      neurotransmission. These two investigations paralleled clinical studies, in both
      cases the results could be predicted correctly ("pro-craving" effect of both
      pharmaceutics). Differences between "symptomatic" and possible "causal" therapies
      are discussed, approaches towards a causal therapy according to an "imprinting"
      model of an addition are suggested.

PMID- 10943907
TI  - Pharmacological validation of a new animal model of alcoholism.
AB  - A new animal model of alcoholism has been developed. Rats derived from this model
      show certain characteristics: (i) they have an incentive demand to consume
      alcohol, (ii) they exhibit relapse-like drinking even after a very long time of
      abstinence, (iii) they show tolerance to alcohol and have mild signs of physical
      withdrawal during the onset of abstinence, and (iv) during abstinence they also
      exhibit a psychological withdrawal syndrome consisting of enhanced anxiety
      related behaviour and hyperreactivity to stressful situations. Anti-craving drugs
      such as acamprosate and naltrexone which proved to be effective in human
      alcoholics to prevent relapse were also effective in our animal model. Thus, both
      compounds suppressed the alcohol deprivation effect which is used as a measure
      for craving and relapse. It is concluded that this pharmacological validation of
      our model demonstrates the predictive value of our model and enables us to
      further characterize putative anti-craving drugs and neurobiological mechanisms
      of addictive behaviour.

PMID- 10943908
TI  - Different allele distribution of a regulatory MAOA gene promoter polymorphism in
      antisocial and anxious-depressive alcoholics.
AB  - Heritable factors account for approximately 40-60% of the total variance of
      liability to alcohol dependence. The present study tested whether a novel
      functional polymorphism in the promotor region of the X-chromosomal monoamine
      oxidase A gene (MAOA) was related to antisocial and anxious-depressive traits in
      alcoholics. Due to the X-chromosomal localization of the MAOA gene,
      psychobiological traits were compared separately for both genders of 298 male and
      66 female alcoholics. In males, 30 of 59 alcoholics with antisocial personality
      disorder carried the low-activity 3-repeat allele in contrast to only 7 of 31
      anxious-depressive alcoholics (51% vs. 23%; p = 0.02). Likewise, female anxious
      depressive alcoholics showed a trend towards a low frequency of genotypes with
      the 3 repeat allele compared to female alcoholics without these symptoms (29% vs.
      53%; p = 0.09). Taken together, these findings suggest that the 3-repeat allele
      of the MAOA polymorphism contributes modestly to the dimension of overand
      underreactive behaviors as possible antecedents of alcoholism.

PMID- 10943909
TI  - Craving for alcohol and dopamine receptor sensitivity in alcohol-dependent men
      and control subjects.
AB  - Detoxified alcohol-dependent men and control subjects were repetitively exposed
      by sight and smell to either a neutral cue (tea) or an alcohol-related cue (their
      favourite alcoholic beverage) to provoke a maximum craving response.
      Additionally, their dopamine receptor sensitivity was evaluated by measuring
      growth hormone (HGH) response to stimulation with the dopamine receptor agonist
      apomorphine (APO). It was hypothesized that the subjects' desire to drink
      (craving) is related to their dopaminergic activity. In both groups, craving
      increased in the presence of the alcohol stimulus with significantly higher
      craving scores in alcoholics than in controls. However, in none of the groups and
      at no cue exposure did the craving response correlate with the individuals'
      dopaminergic activity as reflected by HGH release. Therefore, this study cannot
      add support to the hypothesis that craving for alcohol is associated with
      dopamine receptor sensitivity in abstinent alcoholics or healthy control
      subjects.

PMID- 10943910
TI  - NMDA receptor challenge with dextromethorphan - subjective response,
      neuroendocrinological findings and possible clinical implications.
AB  - Glutamatergic NMDA receptors are believed to play a major role in the
      pathophysiology of numerous neuropsychiatric disorders including substance use
      and schizophrenia. Neuropharmacological studies measuring subjective response,
      psychopathology and biological parameters are helpful in studying pathophysiology
      of these disorders. We report preliminary data of a placebo-controlled double
      blind challenge study in recently detoxified alcoholics (n = 20) and healthy
      controls (n = 10) using the non-competitive NMDA antagonist dextromethorphan.
      Findings suggest that dextrometorphan can produce ethanol-like subjective effects
      in both alcoholics and controls and induce a mild form of craving in alcoholics
      only. The results of this study give further support to the hypothesis of
      glutamatergic NMDA receptors mediating much of ethanol's psychotropic effects.
      Possible clinical implications of these findings are discussed.

PMID- 10943911
TI  - Standardized stimuli to assess drug craving and drug memory in addicts.
AB  - Due to conditioning processes, originally neutral stimuli become drug-associated
      cues and can initiate drug craving. Standardized stimuli are required to assess
      stimulus-induced activation of drug memory and craving in brain imaging and
      neurophysiology studies. We developed substance-specific visual and olfactory
      stimuli for alcohol, tobacco, opiate and cannabis abuse and tested them in
      subjects with the respective addiction and in healthy volunteers. Stimulus
      related drug craving differed significantly between the diagnostic groups and
      indicated that the stimuli are suitable for craving studies.

PMID- 10943912
TI  - Cue exposure in alcohol dependent patients: preliminary evidence for different
      types of cue reactivity.
AB  - Craving is considered to be an important phenomenon in addictive behaviours.
      However, there is still an unresolved debate on what craving for alcohol means,
      how it is best measured and which clinical and therapeutical consequences its
      presence or absence may imply. Cue reactivity paradigms have been developed to
      elicit craving under standardized experimental conditions. Here we present
      preliminary results characterizing alcohol-dependent patients with regard to
      subjective and psychophysiological aspects of exposure to alcohol-associated cues
      in a cue reactivity paradigm. Thirty-six patients fulfilling at least 5 criteria
      of alcohol dependence according to DSM-IV criteria were studied after
      detoxification. Cue reactivity was assessed as subjective (by visual analogue
      scales) and neurophysiological response (by ECG, EMG, electrodermal activity,
      respiratory frequency, salivation) to the presentation of the favourite alcoholic
      beverage or water. While 22% of the patients were both subjective and
      physiological responders, 42% of the subjects showed only a physiological
      reaction without subjective response, and 31% of the patients were neither a
      subjective nor a physiological reaction. Subjective responders to alcohol cues
      had significantly higher state anxiety levels than subjective non-responders.
      These results suggest that alcohol dependent patients may be divided into
      typological subgroups with respect to cue reactivity. Different types of cue
      reactivity might be important for treatment strategies involving repeated cue
      exposure or so-called anti-craving drugs.

PMID- 10943913
TI  - Radiation physics and genetic targeting: new directions for radiotherapy. The
      Douglas Lea Lecture 1999.
AB  - Radiation as a cancer treatment modality is of high physical precision but
      limited biological specificity. Targeted radiotherapy, the delivery of radiation
      to cancer cells by radioisotopes conjugated to tumour-seeking targeting agents,
      is a biologically attractive option but is currently effective for just a few
      tumour types (neuroblastoma, lymphoma) for which efficacious targeting agents are
      available. Radiobiological modelling and radiation microdosimetry have provided
      useful guidelines in choosing treatment strategies for targeted radiotherapy.
      These considerations generally favour the incorporation of targeted radiotherapy
      as one component of a multimodal treatment regimen. Very recently, gene therapy
      techniques have been developed which should enhance the clinical efficacy of both
      external beam radiation and targeted radiotherapy. Typically, non-harmful viruses
      are modified to incorporate therapeutic genes which cause altered cellular
      radiosensitivity or which facilitate the cellular uptake of targeting agents. To
      achieve specificity, therapeutic genes would be co-transfected with tissue
      specific promoter genes causing the therapeutic genes to be expressed in cells of
      particular types. In laboratory models, our research group are exploring the
      transfection-mediated uptake of the targeting agents MIBG and sodium iodide.
      These approaches do not require transfection of every cell in order to cure a
      tumour-cells which have escaped transfection may be sterilized by radiation cross
      fire from transfected neighbours. A new task for radiation microdosimetry is to
      quantify the cross-fire effect and to compute the efficacies of gene transfection
      which will be required for tumour cure. In the spirit of Douglas Lea, the
      analytic approach of physics can be used to illuminate and enhance developments
      in genetics, to the benefit of medicine.

PMID- 10943914
TI  - Conformal intensity-modulated radiotherapy (IMRT) delivered by robotic linac-
      conformality versus efficiency of dose delivery.
AB  - Intensity-modulated radiotherapy (IMRT) may be delivered with a high-energy
      photon linac mounted on a robotic gantry and executing a complex trajectory. In a
      previous paper an inverse-planning technique was developed for such an
      application. Here the work is extended to demonstrate the dependence of
      conformality on the size of the elemental pencil beam, on the complexity of the
      trajectory and on the sampling of azimuth and elevation of the collimated source.
      The improved conformality of complex trajectories is demonstrated and benchmarked
      relative to simpler trajectories, more representative of existing non-robotic
      IMRT techniques. Specifically, by choosing a very fine pencil beam, exquisitely
      conformal dose distributions have been obtained. Important sampling
      considerations have been determined. Expressions have been derived for the
      dosimetry and monitor-unit efficiency of robotic IMRT. Equivalent trajectories
      were computed for executing the complex robotic trajectories instead by using a
      conventional linac. The work benchmarks an ideal in IMRT against which more
      practical and more common techniques may be measured.

PMID- 10943915
TI  - Dynamic splitting of large intensity-modulated fields.
AB  - The aims of this paper are to describe a method of splitting large intensity
      modulated fields that cannot be delivered as a single field and to verify the
      accuracy of our method. Some multi-leaf collimators may be operated in the
      dynamic mode to deliver intensity-modulated radiation treatments (IMRT) using the
      'sliding window' technique. In this technique each pair of leaves sweeps over the
      treatment field while the beam is on. However, there are limitations on the width
      of the field that can be treated due to the limited length of the leaves. For
      instance, the leaf length of the Varian MLC is 14.5 cm. Since each leaf pair must
      travel from the left boundary to the right boundary of the beam aperture, the
      maximum width of the field aperture that can be accommodated in one sweep of
      leaves is also limited to 14.5 cm, in fact to a slightly smaller value. It has
      been shown that IMRT is more efficient when used to plan and deliver the large
      and boost fields simultaneously. In such situations, the fields must be large
      enough to cover simultaneously the volumes of the gross tumour, microscopic
      disease and electively treated regions. Such field sizes are often larger than
      14.5 cm wide. In this paper, we present a dynamic 'feathering' technique to split
      the large intensity-modulated fields into smaller fields. In this technique, the
      component beams overlap each other by a small amount, and the intensity in the
      overlap region gradually decreases for one field component and increases for the
      other. The sum of intensities remains the same as for the original field. This
      method eliminates the field matching problems associated with the conventional
      step 'break' for static fields. The splitting process is integrated into the IMRT
      treatment procedure and the entire planning process is automated. Comparison of
      dose distributions calculated and measured in a phantom showed good agreement.
      Such a method can be applied to the 'step and shoot' technique as well. IMRT
      fields of widths up to 25 cm can be delivered by splitting only once, which is
      adequate for most treatments.

PMID- 10943916
TI  - Monte Carlo dose computation for IMRT optimization.
AB  - A method which combines the accuracy of Monte Carlo dose calculation with a
      finite size pencil-beam based intensity modulation optimization is presented. The
      pencil-beam algorithm is employed to compute the fluence element updates for a
      converging sequence of Monte Carlo dose distributions. The combination is shown
      to improve results over the pencil-beam based optimization in a lung tumour case
      and a head and neck case. Inhomogeneity effects like a broader penumbra and dose
      build-up regions can be compensated for by intensity modulation.

PMID- 10943917
TI  - Use of Monte Carlo computation in benchmarking radiotherapy treatment planning
      system algorithms.
AB  - Radiotherapy treatments are becoming more complex, often requiring the dose to be
      calculated in three dimensions and sometimes involving the application of non
      coplanar beams. The ability of treatment planning systems to accurately calculate
      dose under a range of these and other irradiation conditions requires evaluation.
      Practical assessment of such arrangements can be problematical, especially when a
      heterogeneous medium is used. This work describes the use of Monte Carlo
      computation as a benchmarking tool to assess the dose distribution of external
      photon beam plans obtained in a simple heterogeneous phantom by several
      commercially available 3D and 2D treatment planning system algorithms. For
      comparison, practical measurements were undertaken using film dosimetry. The dose
      distributions were calculated for a variety of irradiation conditions designed to
      show the effects of surface obliquity, inhomogeneities and missing tissue above
      tangential beams. The results show maximum dose differences of 47% between some
      planning algorithms and film at a point 1 mm below a tangentially irradiated
      surface. Overall, the dose distribution obtained from film was most faithfully
      reproduced by the Monte Carlo N-Particle results illustrating the potential of
      Monte Carlo computation in evaluating treatment planning system algorithms.

PMID- 10943918
TI  - Denoising of electron beam Monte Carlo dose distributions using digital filtering
      techniques.
AB  - The Monte Carlo (MC) method has long been viewed as the ultimate dose
      distribution computational technique. The inherent stochastic dose fluctuations
      (i.e. noise), however, have several important disadvantages: noise will affect
      estimates of all the relevant dosimetric and radiobiological indices, and noise
      will degrade the resulting dose contour visualizations. We suggest the use of a
      post-processing denoising step to reduce statistical fluctuations and also
      improve dose contour visualization. We report the results of applying four
      different two-dimensional digital smoothing filters to two-dimensional dose
      images. The Integrated Tiger Series MC code was used to generate 10 MeV electron
      beam dose distributions at various depths in two different phantoms. The observed
      qualitative effects of filtering include: (a) the suppression of voxel-to voxel
      (high-frequency) noise and (b) the resulting contour plots are visually more
      comprehensible. Drawbacks include, in some cases, slight blurring of penumbra
      near the surface and slight blurring of other very sharp real dosimetric
      features. Of the four digital filters considered here, one, a filter based on a
      local least-squares principle, appears to suppress noise with negligible
      degradation of real dosimetric features. We conclude that denoising of electron
      beam MC dose distributions is feasible and will yield improved dosimetric
      reliability and improved visualization of dose distributions.

PMID- 10943919
TI  - 150-250 meV electron beams in radiation therapy.
AB  - High-energy electron beams in the range 150-250 MeV are studied to evaluate the
      feasibility for radiotherapy. Monte Carlo simulation results from the PENELOPE
      code are presented and used to determine lateral spread and penetration of these
      beams. It is shown that the penumbra is comparable to photon beams at depths less
      than 10 cm and the practical range (Rp) of these beams is greater than 40 cm. The
      depth dose distribution of electron beams compares favourably with photon beams.
      Effects caused by nuclear reactions are evaluated, including increased dose due
      to neutron production and induced radioactivity resulting in an increased
      relative biological effectiveness (RBE) factor of < 1.03.

PMID- 10943920
TI  - Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: I. Analysis
      and compensation of eddy currents.
AB  - In BANG gel dosimetry, the spin-spin relaxation rate, R2 = I/T2, is related to
      the radiation dose that has been delivered to the gel phantom. R2 is calculated
      by fitting the pixel intensities of a set of differently T2-weighted base images.
      In gel dosimetry for radiotherapy, an accuracy of 5% in dose and 3 mm spatially,
      whichever is lower, is the objective. Therefore, possible sources of artefacts
      must be considered and dealt with. To obtain a set of base images a multiple spin
      echo sequence is used. However, in a conventional MR scanner eddy currents will
      be provoked by switching the imaging gradients. As the eddy currents change in
      the course of the sequence, the net magnetization will be affected accordingly.
      Hence, eddy currents may have a significant influence on the quantitative R2
      images themselves as well as on their slice position. In this study, we report an
      analysis of the eddy currents as they appear in the multiple spin-echo sequence.
      Eddy currents are measured using a frequency shift method resulting in eddy
      current field maps. The related geometrical displacements are obtained by use of
      a pyramidal phantom. The R2 versus dose relation is determined in the three main
      directions of the magnet, revealing a dependence of the measured R2 on slice
      orientation. The time course of eddy currents is then used in a computer
      simulation to estimate the effects they produce in the recorded R2 images. A
      compensation method for eddy current effects in multi-echo T2 mapping is
      described.

PMID- 10943921
TI  - Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: II. Analysis
      of B1-field inhomogeneity.
AB  - In BANG gel dosimetry, the spin-spin relaxation rate, R2 = 1/T2, is related to
      radiation dose that has been delivered to a gel phantom. R2 is calculated by
      fitting the pixel intensities of a set of differently T2-weighted base images.
      The accuracy that is aimed for in this quantitative MR application is about 5%
      relative to the maximum dose. In a conventional imaging MR scanner, however,
      several imaging artefacts may perturb the final dose map. These deviations
      manifest themselves as either a deformation of the dose map or an inaccuracy of
      the dose pixel value. Inaccuracies in the dose maps are caused by both spatial
      and temporal deviations in signal intensities during scanning. This study deals
      with B1-field inhomogeneities as a source of dose inaccuracy. First, the
      influence of B1-field inhomogeneities on slice profiles is investigated using a
      thin-slice phantom. Secondly, a FLASH sequence is used to map the B1-field by
      assessing the effective flip angle in each voxel of a homogeneous phantom. In
      addition, both experiments and computer simulations revealed the effects of B1
      field inhomogeneities on the measured R2. This work offers a method to correct R2
      maps for B1 -field inhomogeneities.

PMID- 10943922
TI  - Dosimetric characteristics of backscattered electrons in lead.
AB  - In electron beam therapy, tissue overdose due to electrons backscattered from
      lead has been profusely studied. To quantify this dose enhancement effect, an
      electron backscatter factor (EBF) was defined as the ratio of dose at the tissue
      inhomogeneity interface with and without the scatterer present. The dependence of
      the EBF on energy at the scatterer surface is not well known for energies lower
      than 3 MeV which is the most frequent clinical situation. In this work, we have
      done Monte Carlo calculations with the GEANT code to study EBF in lead at this
      energy range. The applicability of this code and the developed procedure for dose
      estimation has been experimentally verified. The dependence of the EBF on the
      beam energy incident on the scatterer has been studied for different nominal beam
      energies incident at the phantom's surface. The results show a trend of increase
      of EBF with the beam energy incident on the scatterer between 0.5 and 1.5 MeV,
      keeping practically constant above this energy up to 3 MeV. Backscattered
      electron energy spectra and depth dose curves in the 'up-stream' direction have
      been obtained at the various energies of the primary electron beam striking on
      the lead scatterer. The results of this work are compared with previously
      published data.

PMID- 10943923
TI  - Dose measurement based on spectral chi-square minimization using GAFchromic MD-55
      film.
AB  - A new method of measuring dose using GAFchromic MD-55-2 type film is proposed. It
      involves 2D fitting of optical density, as a function of both wavelength and
      dose, to a set of measured calibration data. An unknown dose to a film can then
      be determined by minimizing the chi-square between the measured optical densities
      and the fitted calibration data. The methodology was tested, using 60Co
      calibration, by measuring the dose deposited in films irradiated by a 32p source
      in a semi-infinite geometry. The results are compared with the expected dose
      obtained From beta counting, taking into account the dose loss correction due to
      various attenuating materials, including the film substrate itself, which was
      determined to be 20%. It was found that the root mean relative deviation between
      the measured and expected doses was approximately 3%. The excellent agreement
      also demonstrated the possibility of calibration between gamma and beta
      particles.

PMID- 10943924
TI  - Ultraviolet radiation dosimetry with radiochromic film.
AB  - Radiochromic film is tested for its broad-band response to ultraviolet (UV) B
      (290-320 nm) and A (320 nm400 nm), visible and infrared radiation produced by a
      solar simulator and examined for dosimetry in ultraviolet radiation. Results show
      that MD-55-2 radiochromic film in solar and fluorescent light sources responds
      almost exclusively to broad-band UVA radiation with negligible colouration from
      UVB, visible and low level infrared radiation. A second order polynomial function
      approximates the change in optical density at 660 nm wavelength for film
      colouration with exposure to UVA from white light fluorescent and solar UV with
      exposures measured with a dedicated UVA dosimeter. Using a double exposure
      technique as used in radiation dosimetry where the film is firstly irradiated to
      a known UV dose, radiochromic film can be used as a quantitative measure of UVA
      exposure.

PMID- 10943925
TI  - The saturation loss for plane parallel ionization chambers at high dose per pulse
      values.
AB  - The use of plane parallel ionization chambers with electron beams with high dose
      per pulse entails dose uncertainties due to the overestimation of the ion
      recombination factor, k, up to 20% if conventional dosimetric protocols are used.
      In this work MD-55-2 radiochromic films have been used as reference dosimeters to
      obtain dose to water per pulse DGAF(w) values for three Novac7 (Hitesys) electron
      beams of E0 = 5.8 MeV. However, the beam calibration by MD-55-2 films is time
      consuming and the use of plane parallel chambers is fundamental for a periodic
      quality control procedure. Three plane parallel chambers have been used and the
      general formula for the k determination has been tested using the calibration
      doses, DGAF(w). In particular, consistent ion recombination factors ksat(V0)
      (with the ion chamber polarized at V0), that follow the Boag theory, have been
      estimated at different dose per pulse values for the three plane parallel
      ionization chambers. This means that at present any ion chamber needs a specific
      ksat (V0) determination by using a reference dosimeter for which the response is
      independent of the dose rate. An accurate determination of ksat(V0), using a
      reference quality beam, can be used to determine the dose to water per pulse for
      electron beams of different quality and geometrical configuration.

PMID- 10943926
TI  - Water equivalence of plastic organic scintillators in megavoltage radiotherapy
      bremsstrahlung beams.
AB  - Plastic organic scintillators are often considered 'water equivalent' in
      megavoltage photon beams as they have similar atomic composition and density to
      water. Two plastic scintillators are evaluated for their 'water equivalence',
      using the Burlin cavity theory, in the photon energy range of 200 keV to 20 MeV.
      The Burlin theory predicts that the two investigated scintillator materials are
      likely to be 'water equivalent' in the energy range investigated. The prediction
      of the Burlin theory for one of these scintillators has been confirmed by
      absorbed dose measurements in bremsstrahlung beams between 13 and 19 MeV.

PMID- 10943927
TI  - An automated approach to seed assignment for eye plaque brachytherapy.
AB  - Episcleral plaques are commonly used for the treatment of ocular tumours such as
      choroidal melanoma. Treatment planning involves the assignment of seeds to slots
      on the plaque to achieve a desired dose rate distribution. Seed assignment is
      rather straightforward if seeds are ordered on demand. However, the assignment
      task becomes tedious and laborious if the seeds have to be chosen from an
      existing stock of seeds with different activities. To date, this task has usually
      been performed by a human planner through trial and error. An algorithm has been
      developed to automate the task of seed assignment using a mixed-integer
      programming method. We also explore ways to simplify the problem such that the
      method becomes practical in most facilities. We have tested the method on three
      randomly chosen clinical cases from our past records, to show that the algorithm
      could yield solutions within a shorter time frame and with less deviation from
      the desired dose rate distributions, as compared with the solutions from a human
      counterpart.

PMID- 10943928
TI  - Combining two excitation wavelengths for pulsed photothermal profiling of
      hypervascular lesions in human skin.
AB  - When pulsed photothermal radiometry (PPTR) is used for depth profiling of
      hypervascular lesions in human skin, melanin absorption also heats the most
      superficial skin layer (epidermis). Determination of lesion depth may be
      difficult when it lies close to the epidermal dermal junction, due to PPTR's
      limited spatial resolution. To overcome this problem, we have developed an
      approximation technique, which uses two excitation wavelengths (585 and 600 nm)
      to separate the vascular and epidermal components of the PPTR signal. This
      technique permits a noninvasive determination of lesion depth and epidermal
      thickness in vivo, even when the two layers are in close physical proximity to
      each other. Such information provides the physician with guidance in selecting
      the optimal parameters for laser therapy on an individual patient basis.

PMID- 10943929
TI  - Fracture mechanics model of stone comminution in ESWL and implications for tissue
      damage.
AB  - Focused shock waves administered during extracorporeal shock-wave lithotripsy
      (ESWL) cause stone fragmentation. The process of stone fragmentation is described
      in terms of a dynamic fracture process. As is characteristic of all brittle
      materials, fragmentation requires nucleation, growth and coalescence of flaws,
      caused by a tensile or shear stress. The mechanisms, operative in the stone,
      inducing these stresses have been identified as spall and compression-induced
      tensile microcracks, nucleating at pre-existing flaws. These mechanisms are
      driven by the lithotripter-generated shock wave and possibly also by cavitation
      effects in the surrounding fluid. In this paper, the spall mechanism has been
      analysed, using a cohesive-zone model for the material. The influence of shock
      wave parameters, and physical properties of stone, on stone comminution is
      described. The analysis suggests a potential means to exploit the difference
      between the stone and tissue physical properties, so as to make stone comminution
      more effective, without increasing tissue damage.

PMID- 10943930
TI  - The use of tonebursts as an alternative to broadband signals in the measurement
      of speed of sound in human cancellous bone.
AB  - Speed of sound (SOS) measurements, typically made using 1 MHz broadband pulses,
      are increasingly used in the clinical diagnosis of bone disorders. Previous in
      vitro studies indicate that broadband ultrasound pulses are susceptible to
      distortion in cancellous bone, leading to imprecise arrival time and SOS
      measurements. We investigated the effect of bandwidth and frequency on SOS by
      comparing measurements made using 1 MHz broadband with 1 MHz and 300 kHz
      narrowband toneburst signals in 15 human proximal femur cancellous bone
      specimens. There was no significant difference in the value of SOS measured from
      the leading edge of 1 MHz broadband, 1 MHz toneburst and 300 kHz toneburst
      signals. Values of SOS in later regions of 1 MHz and 300 kHz tonebursts fell
      significantly (p < 0.001) when compared to earlier regions. This decrease in SOS
      levelled off by the third complete cycle of 300 kHz toneburst signals, reaching a
      plateau value of 1961 +/- 239 m s-1. No plateau SOS value was obtained in 1 MHz
      tonebursts. The reproducibility of SOS, as measured by the coefficient of
      variation, was higher for later regions of 300 kHz tonebursts than for the
      leading edge of 300 kHz toneburst and 1 MHz broadband signals (p < 0.005). The
      correlation between ultrasound measured modulus and compressive Young's modulus
      improved when 300 kHz tonebursts (r2 = 0.83) rather than 1 MHz broadband (r2 =
      0.77) signals were used to calculate SOS. The improved SOS reproducibility of
      later regions 300 kHz tonebursts suggest that it may be beneficial to use such
      signals rather than 1 MHz broadband pulses in SOS measurement. Since no reliable
      SOS measurements could be obtained from any region of 1 MHz tonebursts, the use
      of high frequency toneburst signals in cancellous bone has little value.

PMID- 10943931
TI  - Coherent scattering and matrix correction in bone-lead measurements.
AB  - The technique of K shell x-ray fluorescence of lead in bone has been used in many
      studies of the health effects of lead. This paper addresses one aspect of the
      technique, namely the coherent conversion factor (CCF) which converts between the
      matrix of the calibration standards and those of human bone. The CCF is
      conventionally considered a constant but is a function of scattering angle.
      energy and the elemental composition of the matrices. The aims of this study were
      to quantify the effect on the CCF of several assumptions which may not have been
      tested adequately and to compare the CCFs for plaster of Paris (the present
      matrix of calibration standards) and a synthetic apatite matrix. The CCF was
      calculated, using relativistic form factors, for published compositions of bone,
      both assumed and assessed compositions of plaster, and the synthetic apatite. The
      main findings of the study were, first, that impurities in plaster, lead in the
      plaster or bone matrices, coherent scatter from non-bone tissues and the
      individual subject's measurement geometry are all minor or negligible effects;
      and, second, that the synthetic apatite matrix is more representative of bone
      mineral than is plaster of Paris.

PMID- 10943932
TI  - Nonlinear cell response to strong electric fields.
AB  - The response of living cells to externally applied electric fields is of
      widespread interest. In particular, the intensification of electric fields across
      cell membranes is believed to be responsible, through membrane rupture and
      reversible membrane breakdown processes, for certain types of tissue damage in
      electrical trauma cases which cannot be attributed to Joule heating. Large
      elongated cells such as skeletal muscle fibres are particularly vulnerable to
      such damage. Previous theoretical studies of field intensification across cell
      membranes in such cells have assumed the membrane current to be linear in the
      applied field (Ohmic membrane conductivity) and were limited to sinusoidal
      applied fields. In this paper, we investigate a simple model of a long
      cylindrical cell, corresponding to nerve or skeletal muscle cells. Employing the
      electroquasistatic approximation, a system of coupled first-order differential
      equations for the membrane electric field is derived which incorporates arbitrary
      time dependence in the external field and nonlinear membrane response (non-Ohmic
      conductivity). The behaviour of this model is investigated for a variety of
      applied fields in both the linear and highly nonlinear regimes. We find that peak
      membrane fields predicted by the nonlinear model are approximately twice as
      intense, for low-frequency electrical trauma conditions, as those of the linear
      theory.

PMID- 10943933
TI  - Transmission of electric and magnetic foetal cardiac signals in a case of ectopia
      cordis: the dominant role of the vernix. caseosa.
AB  - Foetal electrocardiograms (fECGs) and foetal magnetocardiograms (fMCGs) were
      recorded in the 26th, 29th and 31st weeks of gestation from a foetus with ectopia
      cordis-a rare condition in which the heart lies outside the chest wall. This
      provided an opportunity to study foetal cardiograms uninfluenced by the
      insulating effects of the foetal skin and vernix caseosa. The fECG of the ectopia
      cordis foetus was striking. Unlike recordings from age-matched normal foetuses,
      recordings from this subject had very high signal-to-noise ratio and showed no
      anomalous signal transmission properties. In contrast, fMCGs recorded from the
      ectopia cordis foetus and normal foetuses were largely similar. Both showed high
      signal-to-noise ratio and signal transmission properties consistent with volume
      conduction. The findings corroborate the hypothesis that high foetal skin
      resistance due primarily to the vernix caseosa is responsible for the low
      amplitude and anomalous transmission properties of the normal fECG, and
      demonstrate that the fMCG is relatively insensitive to conductivity
      inhomogeneities.

PMID- 10943934
TI  - Distinguishability analysis of an induced current EIT system using discrete
      coils.
AB  - The distinguishability of a discrete coil induced current electrical impedance
      tomography system is analysed. The solution methodology of the forward problem of
      this system is explained. An optimization procedure using this forward problem
      solution is developed to find optimum currents that maximize the
      distinguishability. For the concentric inhomogeneity problem, it is shown that
      the coil currents can be optimized to focus the current density in any desired
      location, in the field of view. Optimum coil currents under the constraints of
      limited peak coil currents and limited total power are determined. Examples that
      demonstrate the performance of the system are presented.

PMID- 10943935
TI  - The performance of a CCD digital autoradiography imaging system.
AB  - Autoradiography is a widely used technique for imaging trace quantities of
      radioactivity within biological samples, conventionally using photographic film.
      This method produces images with high spatial resolution, but it suffers from
      very low sensitivity and poor dynamic range. Digital autoradiography systems with
      greatly improved sensitivity and linearity are commercially available, but the
      spatial resolution is usually much less than that achieved using film. We report
      here the design, construction and characterization of a novel digital
      autoradiography system based on scientific-grade charged coupled devices (CCDs).
      Images of x-ray and beta emissions from radionuclides commonly used in
      autoradiography show that the system can perform high-speed quantitative imaging
      with a spatial resolution of approximately 30, microm. Using a frame by frame
      acquisition method the dynamic range is shown to be at least three orders of
      magnitude. The absolute detection efficiency is comparable to the best of the
      currently available digital systems. CCD images of 125I and 14C radioisotope
      distributions in tissue samples are superior to the equivalent film images and
      have been acquired in 1-10% of the time.

PMID- 10943936
TI  - Design optimization of a breast imaging system based on silicon microstrip
      detectors.
AB  - A mammographic imaging set-up using silicon microstrip detectors in edge-on
      geometry was simulated using the GEANT package. Deposited energy in tissue of
      various thicknesses was evaluated and shown to agree to within 10% with reference
      calculations. Optimal energies as well as spectra for mammography with silicon
      detectors were determined by maximizing the figure of merit of a realistic
      imaging set-up. The scattered to primary radiation ratio was studied for various
      detector geometries. It was found that fan-shaped detectors are needed to
      maintain the image quality for divergent photon beams.

PMID- 10943937
TI  - Mean and variance of single photon counting with deadtime.
AB  - The statistics of photon counting by systems affected by deadtime are potentially
      important for statistical image reconstruction methods. We present a new way of
      analysing the moments of the counting process for a counter system affected by
      various models of deadtime related to PET and SPECT imaging. We derive simple and
      exact expressions for the first and second moments of the number of recorded
      events under various models. From our mean expression for a SPECT deadtime model,
      we derive a simple estimator for the actual intensity of the underlying Poisson
      process; simulations show that our estimator is unbiased even for extremely high
      count rates. From this analysis, we study the suitability of the Poisson
      statistical model assumed in most statistical image reconstruction algorithms.
      For systems containing 'modules' with several detector elements, where each
      element can cause deadtime losses for the entire module, such as block PET
      detectors or Anger cameras, the Poisson statistical model appears to be adequate
      even in the presence of deadtime losses.

PMID- 10943938
TI  - Megavoltage CT imaging as a by-product of multileaf collimator leakage.
AB  - In addition to their potential for the delivery of highly conformal radiation
      therapy treatments, tomotherapeutic treatments also feature increased potential
      for verification. For example, megavoltage CT allows one to use the megavoltage
      linac to generate tomographic images of the patient in the treatment position.
      This is typically done before or after radiation therapy treatments. However, it
      is also possible to collect MVCT images entirely during the treatment itself.
      This process utilizes the leakage radiation through the closed leaves of the
      Nomos MIMiC MLC, along with slight inefficiencies in treatment delivery, to
      generate MVCT images during treatment that require neither additional time nor
      dose. The image quality is limited, yet sufficient to see a patient's external
      boundary, density differences over 8% for 25.0 mm objects and resolutions of 3.0
      mm for high-contrast objects. Such images can potentially be viewed during
      treatment, used to flag additional CT immediately after the treatment and provide
      a representation of the patient's exact position during treatment for use with
      dose reconstruction.

PMID- 10943939
TI  - An optical method of estimating the relative output of a superficial unit for
      small applicators.
AB  - The uncertainties associated with the measurement of the radiation output from a
      superficial x-ray unit are increased when using small applicators, as discussed
      in the text. The method described here uses two stages to measure the relative
      outputs: the first stage uses a large-diameter flat chamber to measure the
      radiation integrated over the applicator end, and the second stage uses an
      optical imaging system to investigate the shape of the beam. These are combined
      to produce a relative output for each applicator, which may then be transformed
      to an absolute output by applying the relative factors to a direct measurement of
      absolute output on one of the larger applicators.

PMID- 10943940
TI  - Comment on 'viability of the EUD and TCP concepts as reliable dose indicators'.

PMID- 10943941
TI  - Reverse micelles as life-mimicking systems.
AB  - In this review, we attempt to demonstrate that reverse micelles are simple
      artificial systems that mimic many life systems from cell division to the
      creation of an enzyme catalytic mechanism. For a membranous enzyme like placental
      alkaline phosphatase, the kinetic properties observed in reverse micelles might
      represent those found under physiological conditions. The reverse micellar
      system, consisting of a positively charged surfactant, mimics a detoxification
      enzyme glutathione transferase. We propose a novel island-in-oil-lake reverse
      micellar model for the glutathione transferase that can account for almost all
      the catalytic properties of this enzyme. Reverse micelles may provide an
      excellent model system in investigating the reaction mechanism of other
      detoxification enzymes.

PMID- 10943942
TI  - Using a heavy chain-loss hybridoma 26.4.1LL for studying the structural basis of
      immunoglobulin chain association.
AB  - One of the mechanisms contributing to antibody diversity is created by the
      association of different heavy and light chains. The combinability of heavy and
      light chains has been studied previously in two systems: in vitro chain
      recombination and hybrid hybridoma. Here, a novel in vivo chain combination assay
      system involving a heavy chain-loss variant, 26.4.1LL, producing two kappa light
      chains (L(DEX) and L(MPC)) different in size is described. In conjunction with
      DNA transfection, immunoprecipitation and SDS-PAGE, the structural basis of
      noncovalent interaction between heavy and light chains can be elucidated
      systematically by examining the relative association tendency of a heavy chain
      with two light chains. To demonstrate the usefulness of this system, three stably
      transfected 26.4.1LL cell lines expressing gamma2b heavy chains, designated as
      H(DEX), H(CHI) and H(ARS), respectively, with structural interrelated variable
      regions were generated: H(DEX) differs from H(CHI) only in framework regions
      whereas H(CHI) differs from H(ARS) in complementarity-determining regions. The
      relative amounts (R values) of L(DEX) and L(MPC) associated with the heavy chains
      H(DEX), H(CHI) and H(ARS) in the assembled immunoglobulin molecules were found to
      be 1.02, 0.64 and 0.05, respectively, suggesting that the complementarity
      determining regions and framework regions contribute equally to the V(L)-V(H)
      interaction. This conclusion is consistent with previous observations based on
      calculation of the buried area in the V(L)-V(H) interface, thus demonstrating the
      usefulness of this system.

PMID- 10943943
TI  - Thermodynamic analysis of human retinal acetylcholinesterase inhibition using an
      anti-Alzheimer's drug, tacrine, through the development of a dual substrate and
      temperature model.
AB  - The present study determines the energy parameters, such as the Gibb's free
      energy change (deltaG), enthalpy change (deltaH), heat of activation (deltaH*),
      entropy change (deltaS), temperature coefficient (Q10) and activation energy
      (Ea), of human retinal acetylcholinesterase (AChE, EC 3.1.1.7) inhibition by
      tacrine. The stereo-frequency collisions factor (PZ, the number of sterically and
      energetically favorable collisions occurring between tacrine and AChE) was also
      studied in this investigation. Tacrine significantly increased the value of
      deltaG, deltaH, deltaH*, Q10, Ea and PZ factor, and decreased the value of deltaS
      for AChE. Since there is no known report on the inhibition of human retinal AChE
      by tacrine, these results were compared with the reported values for the energy
      parameters of camel retinal and chicken brain AChE inhibition by an anti-cancer
      drug, cyclophosphamide. The uniqueness of this approach lies in the development
      of the 'dual substrate and dual temperature' model, which may open up a new, more
      efficient avenue for the study of various enzyme catalyzed reactions.

PMID- 10943944
TI  - Expression of interleukin-2 receptor by activated peripheral blood lymphocytes
      upregulated by the plasma level of interleukin-2 in patients with recurrent
      aphthous ulcers.
AB  - This study used flow cytometry to determine the peripheral blood lymphocyte
      subsets and a sandwich enzyme immunoassay to measure the plasma levels of
      interleukin-2 (IL-2) and soluble IL-2 receptor (sIL-2R) in 34 patients in
      different stages of recurrent aphthous ulcers (RAU) and in 32 age/sex-matched
      normal control subjects. In the exacerbation stage of RAU, a significant increase
      in the percentages of CD3+ (p < 0.001), CD4+ (p < 0.001), CD4+ IL-2R+ (p <
      0.001), CD8+ IL-2R+ (p < 0.01) and IL-2R+ cells (p < 0.001), in the CD4+/CD8+ (p
      < 0.01) and CD4+/CD3+ CD8+ ratios (p < 0.01), and in the plasma level of IL-2 (p
      < 0.001) was found in the patients as compared with the levels in the normal
      control subjects. However, in the post-exacerbation stage of RAU, there was a
      significant decrease in the percentage of CD4+ cells (p < 0.05) and in the
      CD4+/CD8+ (p < 0.01) and CD4+/CD3+ CD8+ ratios (p < 0.001), as well as a
      significant increase in CD8+ cells (p < 0.001) in the patients, as compared with
      the levels in the normal control subjects. Because the CD4+, CD4+ IL-2R+ and CD8+
      IL-2R+ cell counts and the plasma level of IL-2 increased simultaneously in the
      patients in the exacerbation stage of RAU, we suggest that the markedly increased
      plasma level of IL-2 may have been secreted by the increased number of activated
      CD4+ cells, and that the expression of IL-2R by activated peripheral blood
      lymphocytes was upregulated by the plasma level of IL-2 in patients with RAU. In
      addition, the increase and then decrease of the CD4+/CD8+ ratio in the RAU
      patients and the increased number of CD4+ IL-2R+ and CD8+ IL-2R+ activated T
      cells in the RAU patients support the role of cell-mediated cytotoxicity in the
      immunopathogenesis of RAU.

PMID- 10943945
TI  - Central pool of serotonin and tail-flick latency during two phases of biphasic
      fever in rats.
AB  - In experiments on male Wistar rats, the acute phase reaction was induced by a
      bolus intravenous injection of Escherichia coli lipopolysaccharide (10 microg/kg)
      through a silicon catheter pre-implanted into the jugular vein. The colonic and
      skin temperature was measured with thermocouples. Changes in nociception were
      assessed based on tail flick latency (TFL) in response to a noxious heat
      stimulus. In this work, we observed the development of biphasic fever and phasic
      changes in TFL, namely, hyperalgesia in the first period of the acute phase
      reaction and hypoalgesia in its second phase. The catabolism of serotonin
      increased most considerably in the initial period of the acute phase reaction in
      the midbrain, striatum, and rostrodorsomedial medulla (on average, by 20-25%, 35
      40%, and 95-100%, respectively). In the second phase of the acute phase reaction,
      despite a significant increase in the serotonin content in the striatum,
      midbrain, and cerebellum, there were no significant changes in serotonin
      catabolism in these parts of the CNS, which coincided with hypoalgesia. Thus, the
      phasic changes in TFL and colonic temperature after initiation of the acute phase
      reaction were accompanied by determinate changes in the catabolism of serotonin
      in different brain parts.

PMID- 10943946
TI  - Establishment and characterization of a cell line (HCDB-1) derived from a hamster
      buccal pouch carcinoma induced by DMBA and Taiwanese betel quid extract.
AB  - This study identified that the carcinogenesis of hamster buccal pouch (HBP)
      induced by 7,12-dimethylbenz[a]anthracene (DMBA) was greatly enhanced (18 folds)
      by a combination treatment with Taiwanese betel quid (BQ) extract. A new cell
      line, HCDB-1, has been established from induced carcinomas. The cultured
      monolayer cells were epithelioid in shape with irregular nuclei. They
      demonstrated abundant cytokeratin and tonofilaments; however, ultrastructural
      well-organized desmosomes were lacking. The HCDB-1 cell exhibited population
      doubling in 19 h and was highly tumorigenic in nude mice. A C-->T transition at
      codon 141 (Ala to Val) of the p53 gene was detected in this cell. This mutation
      is equivalent to a specific temperature-sensitive mouse p53Ala135Val mutant that
      causes transformation by shifting to 37.5 degrees C. HCDB-1 is the first cell
      line established from the HBP model of oral carcinogenesis induced by
      DMBA/Taiwanese BQ extract. It might be valuable for exploring the molecular
      pathogenesis of oral cancer.

PMID- 10943947
TI  - A model and its implications for denitrification in soil environment.
AB  - We analyzed the mechanisms of a soil nitrogen (N) sub-model, which is a
      subroutine of the Crop-Environment Resources Synthesis (CERES)-maize; a model
      which was originally designed to simulate crop yield and has been calibrated and
      validated in Taiwan. Some experiments designed specifically for testing the N sub
      model proved the capability of the model in reflecting field observations. With
      the mechanisms, we could write computer programs for calculating the relative
      sensitivities of major parameters in the model, and for simulating different
      treatments of organic matter. The purposes were to find how they affected N
      transformations, especially the processes of denitrification, which are
      considered to be responsible for N losses in upland soils and are an important
      environmental issue related to human disturbance of the N cycle. The results
      implied that soil water content and temperature were, respectively, the first and
      second dominant factors. They were much more sensitive than any other parameters,
      such as the decomposition rate coefficients, soil pH and bulk density.
      Decomposition of organic matter could slow down if organic matter with different
      carbon/nitrogen (C/N) ratios were treated in fractions. This treatment could also
      decrease the process of denitrification unless the organic matter was extremely
      large in quantity and has a high C/N ratio.

PMID- 10943948
TI  - Monitoring the changes of redox potential, pH and electrical conductivity of the
      mangrove soils in northern Taiwan.
AB  - The redox potential (Eh), pH and electrical conductivity (EC) of the marsh soils
      of the Chuwei mangrove, located in the estuarine of the Tansui River in northern
      Taiwan were monitored for two years (from October 1995 to September 1997). The
      soils of selected pedons were studied, and the soils were classified based on
      Keys to Soil Taxonomy. The soil pH values tended to be neutral due to the impact
      of seawater on the mangrove marsh. The amounts of organic carbon found in this
      study area were much less than those generally encountered in the wetland soils
      of temperate regions in the world. The base saturation percentages of the soils
      were almost 100%, the exchangeable Na being particularly predominant. The
      concentrations of various cations of water in this ecosystem were in the order of
      Na+ > Mg2+ > K+ = Ca2+, and those of anions of water were in the order of Cl- >
      SO4(2-) > NO3- > PO4(3-). In spite of seasonal flooding changes, highly reduced
      states (100 to -200 mV of Eh values) existed throughout the two-year study. The
      spatial and temporal variations of the Eh values of the surface soil (0-20 cm)
      were higher than those of the subsoils (20-100 cm). The EC values of the soils
      from the surface to a depth of 100-cm were generally more than 20 dS/m. The marsh
      soils of the Chuwei mangrove were, thus, classified as Halic Endoaquents or Halic
      Fluvaquents.

PMID- 10943949
TI  - Muscle function assessment in children.
AB  - Assessment of muscle function has a range of applications, including appraisal of
      the presence and severity of muscle weakness and fatigability, examination of the
      effectiveness of intervention programmes and development and monitoring of
      training programmes. Muscle function assessment is routinely performed in
      rehabilitation, physical education, coaching and research. Procedures have been
      extensively examined in adults, but not in children. The aim of this review is to
      bring to the forefront the issue of paediatric muscle function assessment.
      Objective methods of muscle function assessment are critically analysed with
      specific attention to the issues of applicability, validity and reliability. Each
      of the methods reviewed (isokinetic dynamometry, hand-held dynamometry, field
      tests, and standard weights equipment) has its limitations. All procedures have
      been occasionally studied for validity and reliability and optimal procedures
      have yet to be identified. Methodological limits can be generalized to the type
      and speed of activation, standardization of procedures, subject familiarization,
      gravity and size and psychological influences. It is important for administrators
      of muscle function tests to be aware of the various factors that can both
      influence and confound interpretation. It was concluded that muscle function
      assessment in children requires significant further investigation. Although there
      is a wide range of procedures available, there is limited and equivocal research
      proving validity and reliability. Widespread use of the most valid and reliable
      methods is encouraged. Future research directions are also considered.

PMID- 10943950
TI  - Role of physical activity on health in children and adolescents.

PMID- 10943951
TI  - Oral rehydration for infantile diarrhoea: toward a modified solution for the
      children of the world.

PMID- 10943952
TI  - Selective approach to diagnostic imaging of children after urinary tract
      infection.

PMID- 10943953
TI  - Photoplethysmography: a futuristic view for neonatal care.

PMID- 10943954
TI  - Phototherapy for neonatal jaundice--still in need of fine tuning.

PMID- 10943955
TI  - Bone turnover assessment in infants.

PMID- 10943957
TI  - Comparison of hand-to-leg and leg-to-leg bioelectric impedance devices in the
      assessment of body adiposity in prepubertal children. the STRIP study. Special
      Turku coronary Risk factor Intervention Project.
AB  - The body composition of 40 seven-year-old children and of 50 of their parents was
      measured using two bioelectric impedance devices, the Model 101, RJL Systems, USA
      (conventional hand-to-leg device) and TANITA body fat analyser, TBF 105, Tanita
      Co, Tokio, Japan (newer leg-to-leg device). There were strong correlations
      between impedances obtained by these two devices [r= 0.95, r = 0.93, r= 0.82, r =
      0.81 for girls (n = 22), boys (n = 18), mothers (n = 27) and fathers (n = 23),
      respectively (p < 0.0001 for all)]. However, there was a clear difference in the
      absolute impedance values due to the fact that the devices measure different
      segments of the body. Fat percentages based on built-in equations of the two
      devices correlated in girls, mothers and fathers (r = 0.71, r = 0.94, r = 0.80,
      respectively; p < 0.001) but not in boys (r = 0.21, p = 0.41). Using the Bland
      Altman comparison method, a large intraindividual difference was observed in the
      fat percentages by the two devices, independent of adiposity level. Both devices
      detected significant gender differences in fat percentages in 7-y-old girls and
      boys with similar BMIs. CONCLUSION: When using the Tanita 105 leg-to-leg
      bioelectric impedance device to assess adiposity in children there is an obvious
      need for revised equations. For this, comparative studies using more validated
      methods, i.e. densitometry or DEXA, as part of a multi-compartment model are
      needed.

PMID- 10943956
TI  - Longitudinal changes in 11-13-year-olds' physical activity.
AB  - The influence of age, sex, maturity, body mass and body fatness on the physical
      activity (PA) of 11-13-y-olds was examined longitudinally. Body mass, triceps and
      subscapular skinfold thickness and pubic hair were recorded and 3-d continuous
      heart rate (HR) monitoring was used to estimate PA on each annual measurement
      occasion. At the onset, subjects were 11.0 (0.4)-y-old and data were available on
      202, 143 and 160 subjects in years 1 to 3, respectively with an almost equal sex
      distribution. Multilevel regression modelling examined age-, sex- and maturity
      related changes in time spent with HR above 139 (moderate activity) and 159
      (vigorous activity) bpm. Sustained (10 or 20 min) periods of moderate or vigorous
      activity were not characteristic of PA patterns. Both PA measures declined with
      age, with a consistent sex difference reflecting the lower PA levels of girls.
      Body mass and fatness were not significant explanatory variables, but an
      additional decrement in activity was evident in late maturity. CONCLUSION: Few
      children experience extended bouts of PA, and from 11-13 y, PA decreases, with
      more girls than boys becoming inactive. The data emphasize the importance of
      promoting active lifestyles during youth.

PMID- 10943958
TI  - Evaluation of oral hypo-osmolar glucose-based and rice-based oral rehydration
      solutions in the treatment of cholera in children.
AB  - In a randomized controlled clinical trial, the efficacy of a low-sodium low
      glucose oral rehydration solution (ORS) and a low-sodium rice-based ORS was
      compared with standard WHO glucose ORS in the treatment of severe cholera in
      children aged 2-10y. In total, 120 children were evaluated for the study, of whom
      58 patients were positive for Vibrio cholerae and were included in the study. Of
      these 58 cases, 19 received rice-based hypo-osmolar ORS, 20 received WHO-ORS and
      19 received glucose-based hypo-osmolar ORS. The clinical characteristics (age,
      preadmission duration of diarrhoea, frequency of stool before admission,
      incidence of vomiting, body weight and volume of initial fluid requirement) were
      comparable in the three treatment groups. All patients received tetracycline in a
      dose of 50 mg/kg/d of body weight in 4 divided doses for 3 d. CONCLUSIONS:
      Patients who received rice-based hypo-osmolar ORS had subsequently reduced (p <
      0.05) stool output, ORS consumption and diarrhoea duration than the patients who
      received either WHO-ORS or glucose-based hypo-osmolar ORS.

PMID- 10943959
TI  - Bangladeshi rural mothers prepare safer rice oral rehydration solution.
AB  - Mothers in rural Bangladesh were trained to prepare and use either Rice-ORS (R
      ORS) or Glucose-ORS (G-ORS) solutions to treat children with diarrhoea. Families
      were provided with either G-ORS or R-ORS of the same electrolyte composition
      through a depot holder. Subsequently, random samples of solutions actually used
      for treatment by the mothers were collected from homes by field workers. A total
      of 227 R-ORS and 239 G-ORS samples were analysed. The sodium concentration in
      about 90% of the samples had a safe range (50-120 mmol/l). Only 4% of R-ORS
      solutions were above 120 mmol/l in sodium concentration, while 12% of G-ORS
      solutions exceeded these limits (p < 0.0025). R-ORS (after acid hydrolysis)
      provided significantly higher glucose (257 +/- 42 mmol/l) for active but safe
      absorption compared to G-ORS (115 +/- 39 mmol/l). To make R-ORS liquid enough to
      drink requires addition of sufficient water, preventing the risk of higher sodium
      concentration. Unlike rice starch, glucose is a highly soluble substance. It is
      thus possible to prepare a drinkable solution containing dangerously high
      concentrations of both sodium and glucose, but this can be minimized by more
      intensive training of the mothers.

PMID- 10943960
TI  - Colic in breast-milk-fed infants: treatment by temporary substitution of neocate
      infant formula.
AB  - Infant colic is a common problem characterized by excessive crying and fussing.
      We examined whether colic symptoms of exclusively breast-milk-fed infants would
      be improved by temporary substitution of Neocate, an amino acid-based infant
      formula, for breast milk. Six infants with colic were studied using Barr-type
      infant behavior diaries for a 3-5 d baseline period while they continued
      exclusive breast-milk-feeding, followed by a 4-8 d intervention period of
      exclusive Neocate feeding. All infants showed improvement in distressed behavior
      during intervention; five of the six improved within 1-2 d. For the period after
      1 d of Neocate feeding, the total recorded crying and fussing time was reduced by
      an average of 42%, representing a decrease of 1.0 to 3.1 h daily. A significant
      difference was found between cry and fuss time at baseline versus during
      exclusive Neocate use. Concurrent with Neocate intervention, mothers strictly
      avoided all milk and dairy products. After colic symptoms improved, infants were
      reintroduced to breast milk, which was reasonably well tolerated in four of the
      six infants. Two infants had rapid recurrences of crying and fussing upon return
      to breastfeeding and required an additional period of Neocate feedings before
      subsequent reintroduction to breastfeeding. All infants exhibited colic symptoms
      when directly or indirectly challenged with bovine IgG (BGG), suggesting that BGG
      may play an etiologic role in colic. We propose that a brief intervention with
      Neocate, coupled with strict maternal avoidance of milk and dairy products under
      direct supervision of a lactation consultant, may be an effective treatment for
      colic in some breast-milk-fed infants.

PMID- 10943961
TI  - Cerebrospinal fluid concentrations of alpha-melanocyte-stimulating hormone in
      bacterial and aseptic meningitis.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) has potent anti-inflammatory
      effects in several experimental models of inflammation. It inhibits both the
      actions and production of proinflammatory cytokines and neutrophil migration. We
      investigated whether alpha-MSH in cerebrospinal fluid (CSF) increases during the
      acute stage in patients with bacterial and aseptic meningitis by measuring alpha
      MSH in CSF via radioimmunoassay. The alpha-MSH concentrations in CSF from the
      children with bacterial meningitis who survived (n = 8), those with aseptic
      meningitis (n = 16), and the control subjects (n = 23) were all below the
      detection limit. However, CSF alpha-MSH was elevated in four of the five children
      with bacterial meningitis who had neurological sequelae. We speculate that
      elevated alpha-MSH levels in CSF during acute bacterial meningitis reflect
      negative feedback in response to severe inflammation associated with neurological
      sequelae induced by proinflammatory cytokines. CONCLUSION: CSF alpha-MSH is
      elevated in children with severe bacterial meningitis who had neurological
      sequelae.

PMID- 10943962
TI  - Prediction of vesico-ureteric reflux in childhood urinary tract infection: a
      multivariate approach.
AB  - In this study, independent predictors obtained from patient history, physical
      examination and laboratory results for vesico-ureteric reflux (VUR) in children
      of 0-5 y with a first urinary tract infection (UTI) were assessed and the added
      value of renal ultrasound (US) investigated. Information was collected from
      children visiting the paediatric outpatient department with a first proven UTI,
      defined as a urine monoculture with > or = 10(5) organism/ml, with clinical
      symptoms and possible white cell count > or = 20 per high-power field of spun
      fresh urine. Children with neurologic bladder dysfunction were excluded. VUR was
      determined by voiding cystourethrography (VCUG) and graded from I to V. The
      diagnostic value of predictors was judged using multivariate logistic modelling
      with the area under the receiver operating characteristic (ROC area). A risk
      score was derived based on the regression coefficients of the independent
      predictors in the logistic model. In 140 children (51 boys and 89 girls) VUR was
      diagnosed in 37. Independent predictors for VUR were male gender, age, family
      history for uropathology, serum C-reactive protein level (CRP) and dilatation of
      the urinary tract on US. The ROC area of this model was 0.78 (95% CI: 0.69-0.87).
      This prediction model identified 12% (95% CI: 7-18) of the patients without VUR
      without missing one case of VUR. If we used VUR > or = grade 3 as a threshold,
      the model assessed VUR to be absent in 34% (95% CI: 26-42). CONCLUSION: A
      prediction rule based on age, gender, family history, CRP and US results is
      useful in assessing the probability of VUR in the individual child with a first
      UTI and may help the physician to make decisions about performing additional
      imaging techniques. Prospective validation of the model in future patients,
      however, will be necessary before applying the rule in practice.

PMID- 10943963
TI  - Unilateral multicystic dysplastic kidney disease: defining the natural history.
      Anglia Paediatric Nephrourology Group.
AB  - Controversy exists as to what is the optimal management of antenatally detected
      multicystic dysplastic kidney disease (MCDK): conservative or operative. We
      report 70 (31M, 39F) children with unilateral MCDK in whom the initial
      micturating cystourethrography revealed vesicoureteric reflux into the
      contralateral kidney in 16/63 (25%). Involution of the MCDK kidney was noted at
      birth in 4 and occurred by 2 y of age in 11/46 (24%), with 16/46 (35%) showing a
      significant reduction in size. Of 21 children followed to 5 y, the MCDK had
      disappeared in 3 (14%) and 8 (38%) had shown a further reduction in size. No
      child has developed hypertension or proteinuria. Four children had urinary tract
      infections with lower tract symptoms, but no scarring of the normal hypertrophied
      kidney. We conclude that conservative management of unilateral MCDK is justified
      with long-term follow-up consisting of annual clinical review and ultrasound
      evaluation at 2, 5 and 10 y.

PMID- 10943964
TI  - Cataracts after autologous bone marrow transplantation in children.
AB  - We recorded the incidence and degree of posterior subcapsular cataract (PSC) in
      29 children who had undergone autologous (n = 28) or syngeneic (n = 1) bone
      marrow transplantation (BMT) due to haematologic or lymphoid malignancy.
      Conditioning prior to transplantation consisted either of a combination of
      chemotherapy and total body irradiation (TBI) (n = 21) or of chemotherapy only (n
      = 8). TBI was given in one fraction of 7.5 Gy. Nine patients had received
      previous cranial irradiation. The patients were followed for 4-10y (median 8 y)
      after transplantation. Of 29 patients, 22 developed PSC, all within 4 y after
      BMT. With the exception of one patient who developed unilateral PSC, all had
      received TBI. Conversely, 100% of those who received TBI developed PSC. In this
      group (+TBI), eight patients (38%) developed significant PSC, defined as best
      corrected visual acuity <0.8 in either eye. Six patients (10 eyes) have since
      needed surgical repair consisting of extracapsular cataract extraction and
      intraocular lens implantation. There was no clear relationship between previous
      cranial irradiation and cataract development, nor any other obvious baseline
      differences between those in the +TBI group who developed significant PSC and
      those who did not. Although effects of previous therapy cannot be ruled out, TBI
      appears to be the main cause of PSC in this group of patients. Twelve patients in
      the +TBI group had well-preserved visual acuity throughout the study, reflecting
      a slow progression of PSC. This compares favourably with previous reports of
      allogeneic BMT, possibly owing to less need for corticosteroids after autologous
      BMT. We conclude that the incidence of PSC was high after autologous BMT where
      the conditioning regimen included total body irradiation.

PMID- 10943965
TI  - Effects of cisapride on ventricular repolarization in children.
AB  - Life-threatening ventricular dysrhythmias mainly attributed to QTc prolongation
      have been reported in adults and children who were using cisapride, a prokinetic
      agent that facilitates gastrointestinal motility. Recent adult and paediatric
      case reports have suggested an association of malignant ventricular dysrhythmias
      with administration of cisapride in conjunction with drugs that inhibit its
      cytochrome P-450 metabolism. Therefore, to analyse the time- and dose-related
      effects of cisapride on ventricular repolarization, we prospectively studied
      infants and children receiving cisapride with no concomitant medications.
      Standard 12-lead resting ECGs were obtained from 38 patients (mean age: 6.6 +/-
      4.4 y) before the first dose of cisapride (0.8-1.2 mg/kg/d) therapy, and 3 d, 7 d
      and 1 mo after the first dose of continuing cisapride therapy. The corrected QT
      interval (QTc), dispersion of QT and QTc (QTD, QTcD) were calculated. Patients
      were divided into two groups according to dose of cisapride: Group 1 (n = 22)
      (0.8 mg/kg/d), Group 2 (n = 16) (1.2 mg/ kg/d). Data obtained from these patients
      were compared with a control group consisting of 372 normal children. No clinical
      adverse effects such as palpitations, presyncope or syncope were noted during the
      study. Baseline QTc, QTD and QTcD measurements of the study group were not
      different from those of the control group. Mean QTc values of the study group on
      days 7 and 30 of cisapride therapy were found to be significantly higher than
      those of the control group (p < 0.001 and <0.0001, respectively). Mean QTc values
      of the study group on days 7 and 30 of therapy were also significantly higher
      than those of baseline value (p < 0.01 and <0.001, respectively). Mean QTD and
      mean QTcD values that were recorded throughout the cisapride treatment in the
      study group were not found to be different from the baseline values and the
      values of the controls. Mean QTD and QTcD were also not found to be different
      between Groups 1 and 2. However, mean QTc was found to be more significantly
      increased from baseline at the first month of therapy in Group 2 (p < 0.05). The
      results of this study suggest that cisapride treatment cause prolongation of
      ventricular repolarization without causing increased heterogeneity of
      repolarization (QT dispersion). However, the clinical significance of this effect
      is unclear, because all the patients in this study group remained asymptomatic,
      without signs of dysrhythmia.

PMID- 10943966
TI  - Suitability of the lang II random dot stereotest for detecting manifest
      strabismus in 3-year-old children at child health centres in Sweden.
AB  - The aim of the study is to examine the suitability of the Lang II Random Dot
      Stereotest for use by district nurses in primary healthcare centres. The Lang
      Stereotest is an inexpensive method. It is easy to apply, but the child's co
      operation is required. Approximately 100 district nurses were given detailed
      information and instruction by an orthoptist prior to a randomized population
      based community trial initiated in 1993. In the county of Uppsala in Sweden, all
      4293 children born in 1990 were randomized to one of the following four study
      groups: intervention, control, reliability or validity. All children were
      followed from birth to 6.5 y of age with respect to the occurrence of strabismus.
      The kappa statistic for test-retest reliability among district nurses was 0.65
      (95% CI, 0.51-0.80). A validation of the outcomes of district nurses' against
      orthoptists' examinations using the Lang Stereotest showed a sensitivity of 0.33
      (95% CI, 0.09-0.65) and a specificity of 0.85 (0.80-0.89). Of 113 cases of
      strabismus, 53% were detected within the first 3 y of life. Examination of 1132 3
      y-old children using the Lang Stereotest enabled the district nurses to detect 11
      new cases of strabismus. Only one of these cases was referred to an orthoptist as
      a direct consequence of the screening. The Lang Stereotest showed low reliability
      and low validity in this community trial. It is concluded that the Lang II Random
      Dot Stereotest is not suitable for the screening of manifest strabismus in
      unselected populations of 3-y-old children in Sweden, where a large proportion of
      cases of strabismus is detected during the first 3 y of life.

PMID- 10943967
TI  - Associations between cerebral blood-flow measured by single photon emission
      computed tomography (SPECT), electro-encephalogram (EEG), behaviour symptoms,
      cognition and neurological soft signs in children with attention-deficit
      hyperactivity disorder (ADHD).
AB  - Twenty-eight children with attention-deficit hyperactivity disorder (ADHD) were
      examined with SPECT (single photon emission computed tomography). Seven of the
      children had abnormal distribution of the regional cerebral blood-flow (rCBF) on
      visual evaluation and 10 had abnormal EEG findings. The only clinical finding
      that differentiated the group with normal from abnormal rCBF was behaviour
      symptom load. A factor analysis of the rCBF in different regions of interest
      yielded one factor with low rCBF in the temporal and cerebellar regions and high
      rCBF in the subcortical and thalamic regions, which was significantly associated
      with the degree of motor impairment and results on a cognitive test (WISC).
      Another factor consisting of high rCBF in frontal and parietal regions had a
      significant negative correlation with the degree of behaviour symptoms. There was
      a negative correlation between the rCBF in the right frontal regions and the
      degree of behaviour symptoms. The number of minor physical anomalies (MPA) was
      negatively correlated to the rCBF in the frontal lobes bilaterally. These results
      suggest that there may be at least two functional disturbances in ADHD, one
      specific neurodevelopmentally determined disturbance of the frontal lobes,
      especially of the right hemisphere, related to behaviour deviance, and another
      disturbance of the integration of the temporal lobes, the cerebellum and
      subcortical structures, related to motor planning and aspects of cognition.

PMID- 10943968
TI  - Recognition of facial expressions of emotions in school-age children: the
      intersection of perceptual and semantic categories.
AB  - Recognition of the facial expressions of emotions is a critical communicative
      system early in development and continues to play an important role throughout
      adulthood. In the past, the results of developmental studies of emotional facial
      recognition have often conflicted. The present study was designed to examine the
      development of emotional facial recognition in a large sample of school-aged
      children (n = 120, ages 5-10y). In particular, we investigate whether emotion
      categories, i.e., those based on the visual spatial parameters of facial
      expression, develop in a similar fashion to those that also recruit lexical
      knowledge of emotion terms. We have found two distinct patterns of development
      and we suggest that these different profiles are a consequence of the very
      different cognitive abilities that they recruit. CONCLUSION: Emotion cognition is
      a variegated domain which is differentially related to such areas of cognition as
      visuo-spatial and lexical semantic abilities.

PMID- 10943969
TI  - Characterization of the developmental stages of sucking in preterm infants during
      bottle feeding.
AB  - It is acknowledged that the difficulty many preterm infants have in feeding
      orally results from their immature sucking skills. However, little is known
      regarding the development of sucking in these infants. The aim of this study was
      to demonstrate that the bottle-feeding performance of preterm infants is
      positively correlated with the developmental stage of their sucking. Infants'
      oral-motor skills were followed longitudinally using a special nipple/bottle
      system which monitored the suction and expression/compression component of
      sucking. The maturational process was rated into five primary stages based on the
      presence/absence of suction and the rhythmicity of the two components of sucking,
      suction and expression/compression. This five-point scale was used to
      characterize the developmental stage of sucking of each infant. Outcomes of
      feeding performance consisted of overall transfer (percent total volume
      transferred/volume to be taken) and rate of transfer (ml/min). Assessments were
      conducted when infants were taking 1-2, 3-5 and 6-8 oral feedings per day.
      Significant positive correlations were observed between the five stages of
      sucking and postmenstrual age, the defined feeding outcomes, and the number of
      daily oral feedings. Overall transfer and rate of transfer were enhanced when
      infants reached the more mature stages of sucking. We have demonstrated that oral
      feeding performance improves as infants' sucking skills mature. In addition, we
      propose that the present five-point sucking scale may be used to assess the
      developmental stages of sucking of preterm infants. Such knowledge would
      facilitate the management of oral feeding in these infants.

PMID- 10943970
TI  - Photoplethysmography for simultaneous recording of heart and respiratory rates in
      newborn infants.
AB  - Ten newborn infants, born at 25-41 wk of gestation and nursed in a neonatal
      intensive care unit or in a neonatal intermediate care unit, underwent monitoring
      of heart and respiratory rates with a new technique using an optical sensor, 0-60
      d postnatally. The aim of this study was to compare the heart and respiratory
      rates recorded in infants by photoplethysmography with a probe positioned on
      three monitoring sites, namely the leg, buttock and interscapular region, with
      the rates recorded by ECG and transthoracic impedance, respectively. The
      recordings were compared in order to determine which individual heart beats and
      respiratory cycles were recorded with one or both relevant techniques. A high
      degree of association (r =0.99) was found between the respiratory rates recorded
      by photoplethysmography and by transthoracic impedance. Recordings of heart rates
      by ECG were also highly associated with the photoplethysmographic rates as
      measured at two (r = 0.99) of the three monitoring sites. It is concluded that
      heart and respiratory rates in infants can be monitored satisfactorily by the new
      method based on photoplethysmography. This method offers the advantage of
      recording several physiological parameters non-invasively with a single probe
      during the neonatal period.

PMID- 10943971
TI  - Umbilical artery catheter blood sampling decreases cerebral blood volume and
      oxygenation in very low birthweight infants.
AB  - The aim of this study was to assess whether blood sampling from umbilical artery
      catheters reduces cerebral blood volume and cerebral oxygenation in very low
      birthweight infants. A total of 20 infants, median birthweight 890 g (530-1,500
      g), median gestation age 26 +4 wk (range: 22 +5 to 30 +6 wk) were studied from 10
      min before until 10 min after routine blood sampling from umbilical artery
      catheters placed in the high position. Using near infrared spectroscopy, changes
      in concentrations of cerebral oxygenated and deoxygenated haemoglobin were
      measured, and changes in cerebral blood volume and cerebral oxygenation index
      were calculated. Heart rate, oxygen saturation, transcutaneous PO2 and PCO2 were
      registered continuously. Mean arterial blood pressure was measured before and
      after sampling. Oxygenated haemoglobin decreased significantly from baseline
      during blood sampling, whereas deoxygenated haemoglobin did not change
      significantly. This resulted in a decrease in cerebral blood volume and cerebral
      oxygenation index. Heart rate increased slightly, but significantly, from
      baseline. Oxygen saturation, blood pressure, transcutaneous PO2 and PCO2 did not
      change significantly. CONCLUSION: Blood sampling from umbilical artery catheters
      induces a significant decrease in cerebral blood volume and cerebral oxygenation.

PMID- 10943972
TI  - Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in
      metabolic bone disease of prematurity.
AB  - We wanted to improve detection of low bone mineral density in preterm infants by
      combining serum measurements of total alkaline phosphatase, its bone-type
      isoenzyme and serum inorganic phosphate in a prospective design. The subjects
      were 43 preterm infants. Total and bone isoenzyme activity of alkaline
      phosphatase was determined at 3 wk chronological age and at 3 and 6 mo corrected
      age. The main outcome measure, apparent bone mineral density (BMAD) at the distal
      forearm and forearm shaft, was assessed by dual energy X-ray absorptiometry at 3
      and 6 mo corrected age. An apparent density below 95 mg/cm3 at 3 mo corrected age
      was considered to indicate bone disease, based on the distribution of BMAD values
      of children with non-complicated courses of prematurity. At 3 mo corrected age,
      total alkaline phosphatase activities exceeding 900 IU/l revealed low bone
      mineral density with 88% sensitivity and 71% specificity. Measurements of bone
      isoenzyme activity did not improve diagnostic performance. Serum inorganic
      phosphate levels below 1.8 mmol/l reflected low bone density with high
      specificity (96%), but the sensitivity was only 50%. CONCLUSION: A combination of
      the criteria "serum total alkaline phosphatase activity above 900 IU/l" and
      "serum inorganic phosphate concentrations below 1.8 mmol/l" yielded a sensitivity
      of 100% at a specificity of 70%. This was the best available screening method for
      low bone mineral density in preterms.

PMID- 10943973
TI  - Do phototherapy hoods really protect the neonate?
AB  - The objective of the current study was to evaluate the protection given to the
      eyes of neonates by an Amber 300 phototherapy hood during blue-light phototherapy
      from Drager Phototherapie 800 units, and to make recommendations for clinical
      practice. Hazard-weighted blue-light radiance of phototherapy lamps was measured
      inside neonatal incubators, with and without the use of a protective phototherapy
      hood. The study was carried out in a tertiary referral neonatal unit. No patients
      were involved. A mannequin was used as model of a jaundiced neonate being treated
      with blue-light phototherapy. The study shows that hazard-weighted blue-light
      radiance levels detectable from within the space enclosed by the hood may be
      several times greater than accepted industrial threshold limits for adults.
      CONCLUSIONS: Nursing and medical staff must ensure meticulous care in the
      positioning of infants, so that the caudal edge of the shadow cast by the hood is
      always at least 30 mm inferior to the infants' lower eyelids. The vulnerability
      of the neonatal retina and the relatively high levels of blue-light radiance
      visible from within the shadow of the hood may make it advisable to use more
      effective eye protection. Triple phototherapy using lamps at the foot-end of the
      incubator is clearly hazardous and should not be carried out unless the infant's
      eyes are protected by eye-patches.

PMID- 10943974
TI  - Intracranial hemorrhage associated with vitamin K deficiency in a breastfed
      infant after intramuscular vitamin K prophylaxis at birth. follow-up at 18
      months.

PMID- 10943975
TI  - Infantile form GM1 gangliosidosis with dilated cardiomyopathy: a case report.

PMID- 10943976
TI  - A case of glycogen storage disease type II with double aortic arch.

PMID- 10943977
TI  - Late-onset type II glutaric aciduria with massive pericardial effusion associated
      with severe fatty liver.

PMID- 10943978
TI  - Increase in the prevalence of overweight and obesity from 1995 to 1998 among 18
      year-old males in Sweden.

PMID- 10943979
TI  - Multiple strawberry haemangiomas-side effect of rhuEpo?

PMID- 10943980
TI  - Apple juice as a cause of stress ulcer in a child with Fallot tetralogy.

PMID- 10943981
TI  - Endoscopic endonasal hemisphenoidotomy for resection of pituitary lesions
      confined to the sella: report of 3 cases and technical note.
AB  - The authors report use of a minimally invasive endoscopic procedure, unilateral
      endonasal hemisphenoidotomy, for removal of lesions contained in the sella. The
      entire procedure was performed through a single nostril with the use of an
      endoscope. A unilateral endonasal hemisphenoidotomy (1.5 cm x 1.5 cm) was
      performed and was sufficient to expose the sellar floor for successful removal of
      adenomas confined to the sella in three patients. Neither outfracturing the
      midline septum nor exposure of the opposite sphenoid ostium was necessary for
      adequate visualization, tumor exposure, or instrument maneuverability. There was,
      however, a learning curve required in order to become facile and efficient with
      the equipment. All lesions were completely resected. When compared to a bilateral
      endoscopic endonasal sphenoidotomy as practiced by us, the operative time was
      reduced and the length of stay was 1-2 days. There was less operative trauma,
      patients appeared to experience less pain immediately postoperatively, and their
      satisfaction was very high. In conclusion, for resection of this group of
      intrasellar tumors, the hemisphenoidotomy procedure proved to be less invasive
      and traumatic, more simple, and faster than the standard bilateral endoscopic
      sphenoidotomy.

PMID- 10943982
TI  - Preoperative embolization of hypervascular skull base tumors.
AB  - The purpose of the present study is to review the results and complications of
      preoperative embolization of hypervascular skull base tumors at a neurosurgical
      center with a team of neurosurgeons cross-experienced in the application of both
      microsurgery and endovascular techniques. One hundred and twenty-eight
      endovascular approaches were performed in 66 patients treated for skull base
      meningiomas (n = 41), paragangliomas of the temporal bone (n = 18), and juvenile
      nasopharyngeal angiofibromas (n = 7). One death and 2 permanent disabilities were
      attributable to endovascular therapy. These complications occurred early in our
      experience (1982-1989) and were related to thromboembolic events rather than
      complications of transcatheter embolization itself. Our current standard is to
      perform transfemoral superselective embolizations with either finely corpuscular
      embolizing substances (PVA particles) or cyanoacrylates (NBCA) under local
      anesthesia. Using this protocol no embolization-related complications have
      occurred over the last 9 years. We thus conclude that preoperative embolization
      of hypervascular skull base tumors can be accomplished safely with the
      endovascular techniques now available.

PMID- 10943983
TI  - Ultrasonic contact microprobe: experimental results.
AB  - At the Department of Neurosurgery, School of Medicine, University of Zagreb, the
      original ultrasonic contact microprobe (UCM) was designed. The efficacy of the
      instrument was tested on 120 brains of Wistar strain rats. The authors have been
      investigating the possibility of transferring high-energy ultrasound through the
      titanium wire probe of the device and the efficacy of UCM in controlled
      punctiform destruction of brain tissue. Light and electron microscope assessed
      the lesions made in the brains of experimental rats. Histological findings in the
      preparations showed the zone of thermal injuries from 100 to 200 microm and the
      zone of ultrastructural changes from 200 to 300 microm, indicating the sparing
      effect of the microprobe with regard to the adjacent neurovascular structures.
      The small dimensions of the ultrasonic contact microprobe (1.6 mm) enable its
      introduction through the operating canal of a ventriculoscope. Further research
      is expected to show the efficacy of the ultrasonic contact microprobe in
      endoscopic neurosurgery.

PMID- 10943984
TI  - Endoscopic third ventriculostomy: towards more indications for the treatment of
      non-communicating hydrocephalus.
AB  - OBJECTIVE: Since its reintroduction during the last 2 decades, third
      ventriculostomy has shown promising results. However, with more experience and
      better selection of cases, the indications and contraindications are likely to
      change. METHODS: During the period from November 1994 to December 1996, we have
      treated 27 patients with non-communicating hydrocephalus by endoscopic third
      ventriculostomy at the King Khalid University Hospital. Their ages ranged from 35
      weeks preterm to 26 years of age. Sixteen (59%) patients were one year old or
      younger. Their follow-up ranged from 9 months to 2.5 years. According to the
      etiology of the non-communicating hydrocephalus, patients were divided into 4
      subgroups. These were as follows: 11 aqueduct stenosis, 6 post ventriculitis, 6
      cysts, and 4 posterior fossa tumours. The outcome was graded into 3 grades: Grade
      III were patients who improved after the procedure. Grade II were patients who
      improved after adding a VP-shunt to the procedure. Grade I were failure patients.
      RESULTS: An overall outcome of Grade III was achieved in 22 patients (81%). This
      was broken down according to subgroups as follows: 8/11 (73%) patients of
      subgroup 1, 5/6 in each of the patients of subgroup 2 and 3, and all of the
      patients with posterior fossa tumours. DISCUSSION: The overall results were very
      encouraging and so for the subgroups as compared with the reported cases in the
      literature. CONCLUSION: Better selection of the cases and increased experience
      with the procedure is expected to improve the outcome.

PMID- 10943985
TI  - Endoscopic third ventriculostomy is the treatment of choice for obstructive
      hydrocephalus due to pediatric pineal tumors.
AB  - Pineal lesions in the pediatric patient are often complicated by the development
      of hydrocephalus due to obstruction of the aqueduct or the third ventricle by
      tumor masses. In such cases, hydrocephalus treatment has the highest priority and
      should be performed prior to any surgical treatment of the pineal tumor itself.
      The golden standard in obstructive hydrocephalus treatment remains placement of a
      temporary or permanent cerebrospinal fluid shunt, although there are many long
      term complications associated with a shunt system. To avoid these and to render
      the patients independent from a failure-prone shunt system, we employed
      endoscopic third ventriculostomy for permanent relief of elevated intracranial
      pressure prior to surgical removal of the pineal lesions. The present study
      summarizes the results of this approach in 7 pediatric patients with obstructive
      hydrocephalus. No complications of the endoscopic procedure were encountered, and
      the ventriculostomy remained patent in all cases, as confirmed by motion
      sensitive MRI. The advantages of endoscopic third ventriculostomy as compared
      with other techniques are discussed, and its increasing role in the management of
      children with space occupying lesions of the pineal region is defined.

PMID- 10943986
TI  - Endoscopic ventriculostomy versus shunt operation in normal pressure
      hydrocephalus: diagnostics and indication.
AB  - In contrast to the shunt operation the indication for an endoscopic
      ventriculostomy in patients diagnosed for normal pressure hydrocephalus is not
      scientifically established. Between September 1997 and December 1999 we operated
      on 48 patients diagnosed for normal pressure hydrocephalus. The diagnosis was
      established by means of the intrathecal lumbar or ventricular infusion test, the
      cerebrospinal fluid tap test and MRI-CSF flow studies pre- and postoperatively.
      In 37 patients (77%) we have implanted a ventriculo-peritoneal shunt, and in 11
      patients (23%) we performed the endoscopic assisted third ventriculostomy. With
      our created NPH recovery rate and use of the clinical grading for normal pressure
      hydrocephalus created by Kiefer and Steudel we compared the operative results of
      both groups of patients. In patients with a pathologically increased resistance
      to CSF outflow in the lumbar infusion test a shunt implantation is indicated.
      Patients whose outflow resistance is increased in the ventricular infusion test
      but with a physiological lumbar infusion test are suspected for a functional
      aqueduct stenosis and should be treated by means of endoscopic assisted
      ventriculostomy.

PMID- 10943987
TI  - Endoscope-assisted microsurgery for cerebral aneurysms.
AB  - We performed endoscope-assisted microsurgery for 64 patients with cerebral
      aneurysms from June 1998 to January 1999. Two patients were treated under picture
      in-picture imaging using a surgical microscope connected with an endoscopic-image
      display system. The study included 34 patients with incidental discovery: 3 IC
      oph, aneurysm, 1 from cavernous (C3) portion, 8 at ICPC, 1 from infundibular
      dilatation, 2 at IC bifurcation, 6 at AcoA, 1 at A1A2, 8 at MCA, 1 at P1, 1 from
      basilar tip, 1 at AICA, 1 at VA and 1 from PICA. The study also included 30
      patients with subarachnoid hemorrhage: 5 ICPC, 2 from anterior choroidal, 1 from
      IC infundibular dilatation, 10 from AcoA, 2 from A2A3, 7 from MCA, 2 from basilar
      tip and 1 from PICA. They were classified into gr. 1 for 2, gr. 2 for 8, gr. 3
      for 10, gr. 4 for 7, and gr. 5 for 3 cases.

PMID- 10943989
TI  - Anaesthesiological and criterial care aspects regarding the treatment of patients
      with arteriovenous malformations in interventional neuroradiology.
AB  - In recent years, the neuroradiological treatment of cerebral and spinal
      arteriovenous malformations (AVMs) has undergone significant evolution and
      improvement. Endovascular embolisation procedures of AVMs are mainly performed
      under general anaesthesia. Different pathophysiological characteristics of
      patients with AMVs must be considered for the choice of the anaesthetic
      procedures. Anaesthesiological management must aim at maintaining stable
      intracranial haemodynamics; thus, the drugs used must be evaluated according to
      their effects on brain perfusion, brain metabolism, and intracranial pressure.
      Rapid recovery to normal central nervous functions should be obtained
      postoperatively. Close-meshed neurological surveillance should be exercised in
      order to detect immediately any alteration of neurological state. In summary,
      anaesthesiological management of interventional neuroradiology is based on the
      same well-established principles as anaesthesia in neurosurgery.

PMID- 10943988
TI  - Subdural and intraventricular traumatic tension pneumocephalus: case report.
AB  - Simple pneumocephalus most frequently arises as a complication of a head injury
      in which a compound basal skull fracture with tearing of the meninges allows
      entry of air into the cranial cavity. It can also follow a neurosurgical
      operation. Tension traumatic pneumocephalus with intraventricular extension is an
      extremely rare, potentially lethal condition that requires prompt diagnosis and
      treatment. We report the case of subdural and intraventricular accidental tension
      pneumocephalus occurring in a 26-year-old man as a result of skull fracture. This
      case is combined with rhinorrhea and meningitis that suggest some difficulties to
      treat. The operative procedure associated with medical treatment was performed
      and a good result was obtained.

PMID- 10943990
TI  - Neurosurgery at Fujita Health University, Japan.
AB  - Neurosurgery at the Fujita Health University began in 1972 with Dr. Tetsuo Kanno.
      In 1973, he was joined by Dr. Kazuhiro Katada and in the year 1976, an
      independent neurosurgery department was established with Dr. Kanno as the Chief
      of Neurosurgery. Under his guidance the department continued to grow and by 1978,
      a neurosurgical residency program recognised by the Japanese Board of
      Neurosurgery was established. Integration of laboratory research and clinical
      experience is the hallmark of this program. The current philosophy is directed
      towards subspecialization and academic training. This article provides a brief
      overview of the rapid development of a Neurosurgical Centre to reach
      international acclaim under the guidance of Prof. Tetsuo Kanno.

PMID- 10943991
TI  - RE: Congenital dilatation of the cervical epidural venous plexus: neuroradiology
      and endovenous management.

PMID- 10943992
TI  - Bromocriptine markedly suppresses levodopa-induced abnormal increase of dopamine
      turnover in the parkinsonian striatum.
AB  - Bromocriptine, a dopamine agonist, is commonly used in combination with levodopa
      for the treatment of Parkinson's disease (PD). To investigate the theoretical
      basis of such combination therapy, we examined the effects of bromocriptine
      administered alone or in combination with levodopa on dopamine turnover in the
      striatum of hemi-parkinsonism rats. The parkinsonian striatum showed a 3.4-fold
      increase of dopamine turnover relative to the control striatum, as often observed
      in the brain of PD patients. A 7-day course of levodopa therapy markedly
      increased dopamine turnover in the parkinsonian striatum (53-fold of control
      level) than in the control striatum (5-fold of the control level). However,
      bromocriptine specifically and markedly suppressed the levodopa-induced abnormal
      activation of dopamine turnover in the parkinsonian striatum. Our findings
      explain the pharmacological basis for the introduction of bromocriptine during
      long-term levodopa therapy.

PMID- 10943993
TI  - Optimized binding of [35S]GTPgammaS to Gq-like proteins stimulated with dopamine
      D1-like receptor agonists.
AB  - Subtypes of dopamine D1-like receptors are coupled through the G proteins Gs or
      Gq to stimulate either adenylate cyclase or phospholipase C signaling cascades.
      In the present study, we have uncovered the marked enhancement by sodium
      deoxycholate of D1-like agonist-stimulated [35S]GTPgammaS binding to Gq-like G
      proteins in brain membranes, and determined the optimal experimental conditions
      for assessing agonist effects on [35S]GTPgammaS binding in the presence of the
      detergent. Factors and their optimal levels that were found to significantly
      enhance the sensitivity and robustness of the agonist-stimulated [35S]GTPyS
      binding reaction include protein concentration at 40 microg/ml, cationic
      concentrations of 120 mM Na+, 1.8 mM K+, and 20 mM Mg(2+), a molar guanine
      nucleotide ratio of 100,000 GDP to [35S]GTPgammaS, the presence of 1 mM
      deoxycholate, and an overall incubation duration of 30-120 min. Under the
      optimized conditions, the D1-like agonist SKF38393 induced potent and highly
      efficacious (up to 1000%) stimulation of [35S]GTPgammaS binding in membrane
      preparations from the striatum and other rat brain regions. In striatal membranes
      incubated with drug for 2 h, immunoprecipitation of the [35S]GTPgammaS-bound
      proteins with specific Galpha antibodies showed that at least 70% of SKF38393
      stimulated [35S]GTPgammaS binding was to Galphaq. The present reaction parameters
      are consistent with conditions previously found to support dopaminergic
      stimulation of phospholipase C-mediated signaling in brain slice preparations.
      These results imply that different but equally physiologically relevant
      conditions can be obtained under which subtypes of dopaminergic receptors may
      couple preferentially to Galphas and the adenylate cyclase pathway or to Galphaq
      and the phospholipase C pathway.

PMID- 10943994
TI  - Gas phase oxidants of cigarette smoke increase nitric oxide synthase and xanthine
      oxidase activities of rabbit brain synaptosomes.
AB  - In the present study we demonstrated that NO synthase and xanthine oxidase of
      synaptosomes isolated from rabbit brain cortex can be activated by the gas phase
      of cigarette smoke to produce nitric oxide and superoxide which react together to
      form peroxynitrite. Expose of synaptosomes, up to 3 hours, in the gas phase of
      cigarette smoke, a gradual increase in both nitric oxide and superoxide release
      that were inhibited by N-monomethyl-L-arginine (100 microM) and oxypurinol (1
      mM), respectively, was observed. NO synthase and xanthine oxidase activities were
      increased approximately three fold after treatment of synaptosomes with the gas
      phase of cigarette smoke as compared with the gas phase deprived of oxidants.
      Synaptosomes treated with the gas phase of cigarette smoke dramatically increased
      3-nitrotyrosine production (used as an index of peroxynitrite formation).
      Synaptosomes treated with the gas phase of cigarette smoke, promptly increased
      malondialdehyde production with subsequent decrease of synaptosomal plasma
      membrane fluidity estimated by fluorescence anisotropy of 1,4-(trimethyl-amino
      phenyl)-6-phenyl-hexa-1,3,5-triene. Gas phase deprived of oxidants showed a small
      but not statistically significant (p > 0.05) effect on both malondialdehyde and
      membrane fluidity. In summary, the present results indicate that activation of NO
      synthase and xanthine oxidase of brain cells by oxidants contained in the gas
      phase of cigarette smoke lead to the formation of peroxynitrite a causative
      factor in neurotoxicity.

PMID- 10943995
TI  - Altered ATP hydrolysis induced by pentylenetetrazol kindling in rat brain
      synaptosomes.
AB  - The ectonucleotidase pathway is an important metabolic source of extracellular
      adenosine. Adenosine has potent anticonvulsant effects on various models of
      epilepsy. One of these models is pentylenetetrazol (PTZ) kindling, in which
      repeated administration of subconvulsive doses of this drug induces progressive
      intensification of seizure activity. In this study, we examine the effect of a
      single convulsive injection (60 mg/kg, i.p.) or 10 successive (35 mg/kg, i.p.)
      injections of PTZ on synaptosomal ectonucleotidases. Our results have shown that
      no changes in ectonucleotidase activities were seen at 0, 1, and 24 h or at 5
      days after a single convulsive PTZ injection. However, after PTZ-kindling, rats
      which were more resistant to seizure development presented an increase in ATP
      hydrolysis in synaptosomes from hippocampus and cerebral cortex (44% and 28%,
      respectively). These results suggest that changes in nucleotide hydrolysis may
      represent an important mechanism in the modulation of chronic epileptic activity
      in this model.

PMID- 10943996
TI  - Calpain-PKC inter-relations in mouse hippocampus: a biochemical approach.
AB  - In previous studies, we isolated and identified a mu-calpain/PKCalpha complex
      from rabbit skeletal muscle. Here, we have used specific purification procedures
      in order to study the interactions between mu-calpain and PKC in mouse
      hippocampus, a brain structure implicated in memory processes. We observed that
      mu-calpain and conventional PKCs (alpha, betaII and gamma) are co-eluted after
      anion exchange chromatography. In contrast to our previous results obtained on
      skeletal muscle, mu-calpain and PKC isoenzymes were dissociated after gel
      filtration chromatography. Furthermore, mu-calpain induced the proteolytic
      conversion of PKCalpha, betaII, and gamma into PKMalpha, betaII, and gamma with a
      preferential hydrolysis of PKCgamma, a specific isoenzyme of the nervous system.
      Although the mu-calpain/PKC interactions in the hippocampus are quite different
      from skeletal muscle, our results however, point out the functional importance of
      these inter-relations. Moreover, as PKCgamma has been involved in the biochemical
      events underlying learning and memory, the preferential relationship between mu
      calpain and PKCgamma promotes the importance of the role that mu-calpain could
      play in the cellular mechanisms of memory formation.

PMID- 10943997
TI  - Protection against snake venom-induced neuronal injury by the new hypothalamic
      neurohormone.
AB  - The action of PRP is characterized by the pronounced activation of the background
      activity (BA) of the brain spinal cord, and the degree of the activity depends on
      BA initial level. The typical peculiarity of Vipera raddei venom influence is the
      initial increase in frequency of BA with subsequent depression. A preliminary
      injection of PRP has a protective effect at subsequent influence of venom. In
      animals with hemisection the PRP increases the decreased activity of neurons on
      injury side. Taking into consideration the protective peculiarities of PRP in the
      relationship to snake venom and the possibility of the latter to stabilize and
      prolong the action of drugs (in the case of PRP) combined with them, it is
      supposed that the mentioned use of the combination in clinical practice will be
      perspective. The data obtained testify the PRP to be a neuroprotector against
      many toxic compounds formed in organism (glutamate, ceramid, beta-amyloid
      neurotoxisity, etc.). Investigations in this aspect are still in the process.

PMID- 10943998
TI  - Cerebral taurine release mechanisms in vivo: pharmacological investigations in
      rats using microdialysis for proof of principle.
AB  - Cerebral taurine acts as neurotransmitter, as neuromodulator, or as
      osmoregulator. To investigate its release mechanisms in vivo, we combined the
      microdialysis technique with a variety of experimental paradigms. Taurine release
      was stimulated by either NMDA, NO or a hypotonic solution locally with or without
      the addition of the NMDA antagonists APV or Ketamine, or the NO synthase
      inhibitor L-NAME. Alternatively, the neuroprotective drug lubeluzole was applied
      i.v. NMDA, NO or the hypotonic solution stimulated the release of taurine. NMDA
      mediated taurine release was inhibited by either APV, Ketamine or the NO synthase
      inhibitor L-NAME. Lubeluzole had no effect. Under the hypotonic conditions only
      lubeluzole was effective. These data confirm in vivo that the NMDA-induced
      taurine release is mediated via the NO cascade. By contrast, the release after a
      hypotonic stimulus is not related to the NO cascade. Instead, Na(+)- and/or
      Ca(2+)-mediated events might have been attenuated by lubeluzole.

PMID- 10943999
TI  - Alterations in levels of mRNAs coding for glial fibrillary acidic protein (GFAP)
      and vimentin genes in the central nervous system of hens treated with diisopropyl
      phosphorofluoridate (DFP).
AB  - Diisopropyl phophorofluoridate (DFP) produces organophosphorus-ester induced
      delayed neurotoxicity (OPIDN) in the hen, human and other sensitive species. We
      studied the effect of DFP admimistration (1.7 mg/kg/s.c.) on the expression of
      Intermediate Filament (IF) proteins: Glial Fibrillary Acidic Protein (GFAP) and
      vimentin which are known indicators of neurotoxicity and astroglial pathology.
      The hens were sacrificed at different time points i.e. 1,2,5,10 and 20 days.
      Total RNA was extracted from the following brain regions: cerebrum, cerebellum,
      and brainstem as well as spinal cord. Northern blots prepared using standard
      protocols were hybridized with GFAP and vimentin as well as beta-actin and 18S
      RNA cDNA (controls) probes. The results indicate a differential/spatial/temporal
      regulation of GFAP and vimentin levels which may be due to the result of
      disruption of glial-neuronal network. The GFAP transcript levels reached near
      control levels (88% and 95%) at 20 days post DFP treatment after an initial down
      regulation (60% and 73%) in highly susceptible tissues like spinal cord and
      brainstem respectively. However vimentin transcript levels remained down
      regulated (61% and 53%) at 20 days after an early reduced levels(47% and 55%) for
      spinal cord and brainstem respectively. This may be due to the astroglial
      pathology resulting in neuronal alterations or vice-versa. In cerebellum (less
      susceptile tissue) GFAP levels were moderately down-regulated at 1,2 and 5 days
      and reached near control values at 10 and 20 days. Vimentin was rapidly reinduced
      (128%) in cerebellum at 5 days and remained at the same level at 10 days and then
      returned to control values at 20 days after an initial down-regulation at 1 and 2
      days. Thus these alterations were less drastic in cerebellum as indicated by
      initial susceptibility followed by rapid recovery. On the other hand both GFAP
      and vimentin levels were upregulated from 2 days onwards in the non-susceptible
      tissue cerebrum, implying protective mechanisms from the beginning. Hence the DFP
      induced astroglial pathology as indicated by the complex expression profile of
      GFAP and vimentin mRNA levels may be playing an important role in the delayed
      degeneration of axons or is the result of progressive degeneration of axons in
      OPIDN.

PMID- 10944000
TI  - Effects of neonatal melatonin administration on the extra-hypothalamic regions in
      rat brains: effects on the serotonergic system.
AB  - The effects of 100microg melatonin injection at postnatal day 5 (PD 5) on the
      development of the central serotonergic systems in male and female rats were
      investigated. The contents of serotonin (5-HT) and 5-hydroxy-3-indolacetic acid
      (5-HIAA) were measured in several extrahypothalamic regions at 3, 10 and 42 weeks
      of age. The neonatal melatonin administration increased both 5-HT and 5-HIAA
      levels in the striatum throughout the examined period. In the hippocampus, an
      increase in 5-HIAA contents by neonatal melatonin administration was found at 3
      weeks but not 10 or 42 weeks of age. There were no significant differences in the
      effects of melatonin between male and female rats. These results indicated that
      exogenous melatonin administration during the early neonatal period influenced
      the development of the serotonergic systems in extrahypothalamic regions
      including the hippocampus and the striatum.

PMID- 10944001
TI  - Effects of high-potassium-induced depolarization on amino acid chemistry of the
      dorsal cochlear nucleus in rat brain slices.
AB  - High K+ was used to depolarize glia and neurons in order to study the effects on
      amino acid release from and concentrations within the dorsal cochlear nucleus
      (DCN) of brain slices. The release of glutamate, gamma-aminobutyrate (GABA) and
      glycine increased significantly during exposure to 50 mM K+, while glutamine and
      serine release decreased significantly during and/or after exposure,
      respectively. After 10 min of exposure to 50 mM K+, glutamine concentrations
      increased in all three layers of DCN slices, to more than 5 times the values in
      unexposed slices. In the presence of a glutamate uptake blocker, L-trans
      pyrrolidine-2,4-dicarboxylic acid (PDC), glutamine concentrations in all layers
      did not increase as much during 50 mM K+. Similar but smaller changes occurred
      for serine. Mean ATP concentrations were lower in 50 mM K(+)-exposed slices
      compared to control. The results suggest that depolarization, such as during
      increased neural activity, can greatly affect amino acid metabolism in the
      cochlear nucleus.

PMID- 10944002
TI  - Effect of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) on human
      serotonergic cells.
AB  - The tryptamine-derived dopaminergic neurotoxin 1-trichloromethyl-1,2,3,4
      tetrahydro-beta-carboline ('TaClo'), which was found to occur in humans after
      intake of the hypnotic chloral hydrate, was also shown to strongly disturb
      serotonergic cells. Incubation experiments using the human serotonergic cell line
      JAR clearly revealed TaClo to significantly reduce serotonin (5-HT) uptake
      (IC(50) = 59 microM) and to induce a distinct loss of cellular viability at
      increasing TaClo concentrations. In contrast to well-known serotonergic
      neurotoxins such as amphetamines, however, TaClo toxicity is not mediated by the
      5-HT transporter (5-HTT). In the presence of the specific 5-HTT inhibitor
      imipramine, the uptake of TaClo into JAR cells was not reduced, hinting at an
      exclusively passive penetration of this highly lipophilic beta-carboline through
      cell membranes. Similar toxic effects towards JAR cells were also observed for
      the 5-HT-related TaClo analog 6-hydroxy-1-trichloromethyl-1,2,3,4-tetrahydro-beta
      carboline ('6-OH-TaClo') (IC50 = 26 gM). The dopamine-derived alkaloid-type
      heterocycle 6,7-dihydroxy-1-trichloromethyl-1,2,3,4-tetrahydroisoquinoline
      ('DaClo'), by contrast, was found to be less toxic, showing only a weak
      inhibitory activity (IC50 = 260 microM) on 5-HT uptake. The pronounced toxicitiy
      of TaClo and 6-OH-TaClo against serotonergic cells became also evident from
      morphological findings: Dose-dependently, the survival of JAR cells was
      significantly impaired, while human dopaminergic IMR-32 cells were only
      moderately affected at similar toxin concentrations.

PMID- 10944003
TI  - Effects of carmustine and lomustine on arylamine N-acetyltransferase activity and
      2-aminofluorene-DNA adducts in rat glial tumor cells.
AB  - Carmustine and lomustine are nitrosourea antitumor chemotherapeutic agents which
      were used to determine whether or not they could affect arylamine N
      acetyltransferase (NAT) activity and DNA-2-aminofluorene adducts in rat glial
      tumor cell line (C6 glioma). The NAT activity was measured by high preformance
      liquid chromatography (HPLC) assaying for the amounts of N-acetyl-2-aminofluorene
      (AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and remaining 2-aminofluorene
      (AF) and p-aminobenzoic acid (PABA). The results indicate that NAT activity in
      glial tumor cell cytosols and intact tumor cells were decreased by carmustine and
      lomustine in a dose-dependent manner. The apparent values of Km and Vmax of NAT
      from rat glial tumor cell also decreased after co-treatment of carmustine and
      lomustine in both examined cytosols and intact cells. Following exposure of glial
      tumor cells to the various concentrations of AF with or without co-treatment with
      carmustine and lomustine, DNA-AF adducts were determined by using gamma-[32p]
      dATP and HPLC. The DNA-AF adducts in rat glial tumor cells were decreased by co
      treatment with carmustine and lomustine. This report is the first demonstration
      to show carmustine and lomustine did inhibit rat glial tumor cells NAT activity
      and DNA-AF adduct formation.

PMID- 10944004
TI  - Human, bovine, and rabbit retinal glutamate-induced [3H]D-aspartate release: role
      in excitotoxicity.
AB  - The pharmacological basis of glutamate-induced [3H]D-aspartate release was
      investigated in isolated human, bovine and rabbit retinas. Isolated mammalian
      retinas were preloaded with [3H]D-aspartate and then prepared for studies of
      neurotransmitter release using the superfusion method. Release of [3H]D-aspartate
      was elicited by K+ (50 mM) or by L-glutamate. In bovine retinas, L-glutamate, but
      not D-glutamate induced an overflow of [3H]D-aspartate that was partially
      inhibited by low external calcium, omega-conotoxin (10 nM) or nitrendipine (1
      microM). Metabotropic glutamate receptor (GLUR) agonists also evoked [3H]D
      aspartate release in both bovine and human retinas whereas polyamines only
      enhanced the excitatory effects of L-glutamate on [3H]D-aspartate release.
      Antagonists of GLURs and the polyamine site inhibited L-glutamate evoked [3H]D
      aspartate overflow with the following rank order of potency: MCPG >ifenprodil >
      AP-5 > arcaine> MK-801. In conclusion, L-glutamate-induces a stereoselective,
      calcium-dependent release of [3H]D-aspartate from isolated mammalian retinas that
      can be mimicked by GLUR agonists (and blocked by both receptor and polyamine site
      antagonists).

PMID- 10944005
TI  - Increased AP-1 DNA-binding activity and nuclear REF-1 accumulation in lead
      exposed primary cultures of astrocytes.
AB  - Pb was shown to perturb neuronal and glial function either directly by
      interacting with protein thiol groups or indirectly by mimicking Ca(2+) and
      increasing oxidative stress. In view of the potential action of Pb on cellular
      redox homeostasis we studied the regulation of activator protein-1 (AP-1) DNA
      binding. A 1h incubation of astrocyte primary cultures with 10 microM Pb caused a
      2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elicited this
      increase revealed the involvement of 1. transcriptional and 2. posttranslational
      processes. The first one was documented by an increase of c-jun mRNA content
      after 15 to 30 min of 10 microM Pb exposure. The second one was suggested by an
      enhanced nuclear accumulation of redox factor-1 after 30 to 60 min of 10 microM
      Pb exposure. The Pb-elicited increase of the reduction/oxidation-sensitive AP-1
      signal transduction may regulate target genes operative in cell survival or cell
      death.

PMID- 10944006
TI  - Effect of in vivo administration of naloxone on ATP-ase's enzyme systems of
      synaptic plasma membranes from rat cerebral cortex.
AB  - Naloxone is a specific competitive antagonist of morphine, acting on opiate
      receptors, located on neuronal membranes. The effects of in vivo administration
      of naloxone on energy-consuming non-mitochondrial ATP-ases were studied in two
      different types of synaptic plasma membranes from rat cerebral cortex, known to
      contain a high density of opiate receptors. The enzyme activities of Na+, K(+)
      ATP-ase, Ca(2+), Mg(2+)-ATP-ase and Mg(2+)-ATP-ase and of acetylcholinesterase
      (AChE) were evaluated on synaptic plasma membranes obtained from control and
      treated animals with effective dose of naloxone (12microg x kg(-1) i.m. 30
      minutes). In control (vehicle-treated) animals specific enzyme activities assayed
      on these two types of synaptic plasma membranes are different, being higher on
      synaptic plasma membranes of II type than of I type, because the first fraction
      is more enriched in synaptic plasma membranes. The acute treatment with naloxone
      produced a significant decrease in Ca(2+),Mg(2+)-ATP-ase activity and an increase
      in AChE activity, only in synaptic plasma membranes of II type. The decrease of
      Ca(2+), Mg(2+)-ATP-ase enzymatic activity and the increased AChE activity are
      related to the interference of the drug on Ca(2+) homeostasis in synaptosoplasm,
      that leads to the activation of calcium-dependent processes, i.e. the extrusion
      of neurotransmitter. These findings give further evidence that pharmacodynamic
      characteristics of naloxone are also related to increase [Ca(2+)]i, interfering
      with enzyme systems (Ca(2+), Mg(2+)-ATP-ase) and that this drug increases
      acetylcholine catabolism in synaptic plasma membranes of cerebral cortex.

PMID- 10944007
TI  - Differential incorporation of precursor moieties into cerebral cortex and
      cerebellum glycerophospholipids during aging.
AB  - The incorporation of polar and non-polar moieties into cerebral cortex (CC) and
      cerebellum (CRBL) phospholipids of adult (3.5-month-old) and aged (21.5-month
      old) rats was studied in a minced tissue suspension. The biosynthesis of acidic
      phospholipids through [3H]glycerol appears to be slightly increased with respect
      to that of zwitterionic or neutral lipids in CC of aged rats with respect to
      adult rats. On the contrary, the synthesis of phosphatidylcholine (PC) from
      [3H]choline was inhibited. However, the incorporation of [14C]serine into
      phosphatidylserine (PS) was higher in CC and CRBL in aged rats with respect to
      adult rats. The synthesis of phosphatidylethanolamine (PE) from PS was not
      modified during aging. Saturated ([3H]palmitic) and polyunsaturated
      ([3H]arachidonic) acids were incorporated successfully by adult and aged brain
      lipids. In addition [3H]palmitic, [3H]oleic and [3H]arachidonic acid were
      employed as glycerolipid precursors in brain homogenate from aged (28.5 month
      old) and adult (3.5 month old) rats. [3H]oleic acid incorporation into neutral
      lipids (NL) and [3H]arachidonic acid incorporation into PC, PE and
      phosphatidylinositol (PI) were increased in aged rats with respect to adult rats.
      Present results show the ability and avidity of aged brain tissue in vitro to
      incorporate unsaturated fatty acids when they are supplied exogenously. They also
      suggest a different handling of choline and serine by base exchange enzyme
      activities to synthesize PC and PS during aging.

PMID- 10944009
TI  - Tc-99m MAG3 evaluation of recipients with En bloc renal grafts from pediatric
      cadavers.
AB  - Tc-99m MAG3 scintigraphy is a well-established test to monitor patients who have
      received renal grafts. The shortage of available kidneys has forced the
      development of alternative sources of donors. En bloc pediatric renal grafts have
      been used for more than 10 years with good results, but mechanical complications
      are still a concern. No reports have illustrated the Tc-99m MAG3 scintigraphic
      aspect of the most common complications resulting from en bloc pediatric renal
      grafts. The authors describe three recipients of en bloc renal graft. One patient
      had thrombosis of one of the two grafts, one patient had postrenal obstruction of
      only one of the grafts, and a third patient progressed normally.

PMID- 10944008
TI  - The use of permeabilized cells to assay protein phosphorylation and catecholamine
      release.
AB  - A number of approaches can be used to determine the protein kinases and protein
      phosphatases acting on particular phosphoproteins in vivo. Cell permeabilization
      represents one such approach. In this overview we discuss the different
      permeabilization procedures used in bovine adrenal chromaffin cells and in
      particular the use of digitonin. The effect of various factors on the extent of
      digitonin-permeabilization, protein phosphorylation and catecholamine release are
      also discussed. The factors include the permeabilization medium, the ions such as
      calcium, and the second messengers, such as cAMP, IP3, cADPR and calmodulin. The
      effect of specific peptide inhibitors of protein kinases on tyrosine hydroxylase
      phosphorylation is illustrated. Advantages and disadvantages of cell
      permeabilization procedures are discussed throughout the text.

PMID- 10944010
TI  - False-positive results obtained with stress myocardial SPECT in patients with
      right bundle branch block.
AB  - PURPOSE: Right bundle branch block (RBBB) is a conduction defect that often is
      accompanied by nonspecific patient symptoms. The objective of this study was to
      evaluate the false-positive results obtained with TI-201 myocardial SPECT in
      patients with RBBB. METHODS: Thirty-one patients (24 men, 7 women; age range, 35
      to 78 years; mean age, 39 +/- 14 years) had nonspecific chest pain and
      electrocardiograph-proved RBBB, normal results of echography, and normal results
      of coronary angiography. None of them had a previous history or evidence of
      myocardial infarction. All patients underwent stress-rest TI-201 myocardial
      SPECT; 24 had normal images but 7 showed hypoperfusion in the inferolateral
      segments, both visually and quantitatively. RESULTS: TI-201 myocardial perfusion
      scintigraphs must be evaluated carefully in RBBB because false-positive results
      are likely to occur as a result of functional changes produced by dissynchronous
      activation between the ventricles.

PMID- 10944011
TI  - Indium-111 platelet scintigraphy in a patient with chronic disseminated
      intravascular coagulation.
AB  - The authors describe a relation between the in vivo localized consumption of In
      111 platelets and results of laboratory tests in a 82-year-old man with an aortic
      graft prosthesis who had chronic disseminated intravascular coagulation. In-111
      platelets accumulated markedly over the abdominal aortic graft with a shortened
      platelet survival time and reflected changes in hematologic studies, which showed
      low platelet counts and a high concentration of fibrinogen degradation products
      in the plasma. If a strong clinical likelihood of local disseminated
      intravascular coagulation exists, then In-111 platelets may be valuable in
      localizing the focus of platelet consumption.

PMID- 10944012
TI  - Language mapping in pretreatment planning of patients with cerebral arteriovenous
      malformation: a PET study.
AB  - PURPOSE: Three patients who had cerebral arteriovenous malformations underwent
      language mapping by positron emission tomography (PET) to identify the dominant
      hemisphere for language and the spatial relation of lesions to language areas.
      METHODS: Mapping was performed to assess the risk that surgery could cause
      neurologic deficits and to plan other therapeutic strategies. RESULTS: The
      information obtained by PET language mapping changed the course of management for
      these patients. Two patients were treated with stereotactic radiosurgery and one
      patient with surgical resection. CONCLUSIONS: PET imaging can be a valuable
      noninvasive tool for mapping the functional cortex and for preoperative planning
      of different treatment options in patients with arteriovenous malformations.

PMID- 10944013
TI  - Regional cerebral glucose metabolism in healthy volunteers determined by
      fluordeoxyglucose positron emission tomography: appearance and variance in the
      transaxial, coronal, and sagittal planes.
AB  - PURPOSE: In this study, the contribution of the transaxial, coronal, and sagittal
      planes in evaluations of regional cerebral glucose metabolism was investigated in
      healthy volunteers as determined by fluorine-18-labeled 2-deoxy-2-fluoro-D
      glucose (FDG) and high-resolution positron emission tomography (PET). METHODS:
      One hundred twenty-seven healthy right-handed volunteers were injected with 4.2
      MBq/kg (0.11 mCi) body weight FDG and imaged in a PENN PET H 240 scanner. Images
      were corrected for scatter and random coincidences and reconstructed in all three
      planes into 6- to 8-mm-thick slices. The reconstructed images were corrected for
      attenuation using the Chang algorithm. The transverse, coronal, and sagittal
      images were read independently of each other using a qualitative scale in which 1
      = equal to, 2 = mildly, 3 = moderately, and 4 = markedly less than the area with
      the highest glucose metabolism in the respective plane. RESULTS: The areas with
      the highest glucose metabolisms were the posterior cingulate gyri with mean
      scores of 1.1 to 1.2, thalami (1.2 to 1.3), basal ganglia (1.5 to 1.9), and
      visual cortex (1.6). The lowest values were found in the occipital cortex (2.7 to
      2.8) and the cerebellum (2.3 to 2.4). Whereas reliable analysis of the mesial
      temporal aspects was not feasible in the sagittal plane, the anterior poles of
      the temporal and frontal lobes could not be evaluated in the coronal or the
      inferior temporal areas in the transaxial slices. In all three planes, regional
      glucose metabolism was less in the lateral temporal areas on the left than on the
      right (P < 0.001). The consistency of readings as measured in terms of
      coefficients of variation was greatest in the coronal plane for the caudates and
      posterior cingulate gyri, in the transaxial plane for the lateral temporal
      regions, and in the sagittal plane for the visual cortex. Age-dependent decreases
      in regional glucose metabolism in the inferior and lateral frontal regions and
      the parietal lobes were found in all three planes. CONCLUSIONS: All three
      projection planes must be used for a comprehensive qualitative evaluation of the
      regional glucose metabolism of the brain.

PMID- 10944015
TI  - Diffuse, intense lung uptake on a bone scan: a case report.
AB  - PURPOSE: Clinical and scintigraphic findings are described in a patient with
      unexpected diffuse lung uptake on bone scan after a heroin overdose. METHODS: The
      patient's Tc-99m MDP bone scan is reviewed along with the pertinent clinical
      history and laboratory findings. RESULTS: Marked diffuse and symmetric lung
      uptake is present on bone scintigraphy in a patient with a history of acute renal
      failure and a markedly elevated calcium-phosphate product but normal renal
      function and laboratory values at the time of the examination. CONCLUSIONS: The
      incidental observation of metastatic calcification by bone scintigraphy is
      important, because it may aid in the diagnosis of a previously unsuggested
      elevated calcium-phosphate product, renal failure, or both. Furthermore, the
      intensity of tracer localization on bone tracer-specific imaging may help
      evaluate the activity of the metastatic calcification process.

PMID- 10944014
TI  - Refinement of the positive predictive value of gallbladder nonvisualization after
      morphine administration for acute cholecystitis based on the temporal pattern of
      common bile duct activity.
AB  - The authors previously reported two major patterns in the time-activity curve of
      the common hepatic bile duct (BD) after morphine administration in patients with
      gallbladder nonvisualization. The first pattern consists of a gradual increase in
      BD activity (of variable duration) occurring during a simultaneous decrease in
      liver parenchymal activity (BD increase), representing the physiologic effects of
      morphine administration. The second pattern consists of a continuous decrease in
      BD activity that parallels the activity in the liver parenchyma (BD decrease),
      representing lower or no physiologic effects of morphine administration. The
      authors hypothesize that gallbladder nonvisualization associated with a
      continuous decrease in BD activity after morphine administration will have a
      lower positive predictive value (PPV) for acute cholecystitis than gallbladder
      nonvisualization associated with an increase in BD activity. METHODS: Thirty-six
      patients who had morphine-augmented cholescintigraphy were divided into two
      groups: 19 with BD increase after morphine administration and 17 with BD
      decrease. RESULTS: Of the 36 patients, 22 had acute cholecystitis. The positive
      predictive value (PPV) of gallbladder nonvisualization was 61%. All of the
      remaining 14 had chronic cholecystitis. Of 19 patients with BD increase, 15 had
      acute cholecystitis (PPV = 79%), whereas only 7 of 17 patients with BD increase
      (PPV = 41 %) had acute cholecystitis (P = 0.023 by the one-tailed and 0.038 by
      the two-tailed Fisher exact tests). CONCLUSIONS: Gallbladder nonvisualization
      after morphine administration with the pattern of BD decrease is not as reliable
      (intermediate probability in this series) for the diagnosis of acute
      cholecystitis as is nonvisualization of the gallbladder in patients with a
      pattern of BD increase (high probability).

PMID- 10944016
TI  - Vertebral hemangioma mimicking a metastatic bone lesion in well-differentiated
      thyroid carcinoma.
AB  - The authors report a case of abnormal accumulation of I-131 in a thoracic
      vertebra in a patient with a well-differentiated thyroid carcinoma. The
      presumptive diagnosis was metastatic bone disease. Further diagnostic work-up
      confirmed a benign bone lesion. Bone metastasis, when shown on I-131 whole-body
      scintigraphy, usually supports a change in the staging and therapeutic approach
      to a patient with thyroid carcinoma. The authors believe that, although an
      infrequent lesion, the differential diagnosis of abnormal accumulation of I-131
      in the body of a vertebra in patients with well-differentiated thyroid carcinoma
      should raise the possibility of a benign hemangioma. Complete work-up of the
      suggested bone metastatic lesion should be performed before tumor restaging and I
      131 therapy is recommended.

PMID- 10944018
TI  - Fluorine-18 FDG myocardial positron emission tomographic findings before and
      after pituitary adenoma resection in a patient with acromegalic cardiomyopathy.
AB  - Because of persistently elevated growth hormone levels, acromegaly gives rise to
      various changes in organs mediated by insulin-like growth factor-I. In the heart,
      it causes myocardial hypertrophy, and, with time, heart failure. The authors
      performed pituitary adenomectomy in a patient with acromegalic cardiomyopathy who
      had heart failure; after operation, the blood growth hormone levels decreased to
      within the normal range and there was a marked improvement in left ventricular
      function by gated blood pool scintigraphy. Pre- and postoperative fluorine-18
      fluorodeoxyglucose (FDG) myocardial positron emission tomography showed increased
      accumulation of FDG in the myocardium before surgery, but accumulation within the
      normal range after operation. Myocardial glucose metabolism changed when the long
      term effects of growth hormone and insulin-like growth factor-I were eliminated,
      and this appears to be accurately reflected by FDG positron emission tomography.

PMID- 10944017
TI  - A prospective study of Tc-99m MIBI in the differential diagnosis of pelvic masses
      in female patients.
AB  - PURPOSE: This study evaluated the feasibility of Tc-99m MIBI scintigraphy in the
      differential diagnosis of pelvic masses in female patients before operation.
      METHODS: Seventy-one patients with pelvic masses were studied with planar imaging
      over the abdomen and pelvis 5, 15, 30, and 60 minutes after injection of 740 MBq
      (20 mCi) Tc-99m MIBI. The uptake of the masses was graded, and other abnormal
      signs, such as intestinal involvement, lymph node involvement, or peritoneal
      fluid collection, were also considered in image interpretation. An exploratory
      laparotomy was performed 3 days to 2 weeks after imaging. The scintigraphic
      diagnosis was compared with that of computed tomography (CT), CA-125 measurement,
      and pathologic analysis. RESULTS: Forty-one of 46 pelvic masses with no activity
      were proved benign. Eighteen of 25 with a fixed, focal uptake were malignant. In
      19 of 23 masses, intestinal activity noted within 30 minutes was caused by
      metastases. All three cases with lymph node involvement and six cases with
      ascites were confirmed malignant. Combining focal uptake with intestinal
      involvement correctly indicated 22 of 23 malignant conditions before operation,
      whereas negative scans identified 41 of 48 benign lesions. Four of seven false
      positive lesions had a higher cellular component. The diagnostic performance of
      Tc-99m MIBI is better than that of CT and CA-125 tests, because CT had eight
      false-positive and three false-negative results, whereas CA-125 had 12 false
      positive and 3 false-negative results, respectively. CONCLUSIONS: Tc-99m MIBI is
      useful for differentiating benign and malignant pelvic masses in female patients.
      A fixed focal uptake or intestinal uptake of the radiotracer suggests malignancy,
      with diagnostic sensitivity, specificity, accuracy, and positive and negative
      predictive values of 95.6%, 85.4%, 88.7%, 75.9%, and 97.6%, respectively, in the
      current prospective study.

PMID- 10944019
TI  - Scintigraphy of popliteus bursitis.

PMID- 10944020
TI  - A massive cystic dysplastic kidney shown on a DMSA scan: incremental value of
      early and delayed views in preventing misdiagnosis.

PMID- 10944021
TI  - Diagnosis of horseshoe kidney not shown on ultrasound but clearly visualized by
      renal scintigraphy.

PMID- 10944022
TI  - Acute trauma-induced fracture of the C7 spinous process shown by bone
      scintigraphy.

PMID- 10944023
TI  - The detection of vesicoureteral reflux in the nonfunctioning lower half of an
      occult' duplex kidney by Tc-99m MAG3 indirect radionuclide cystography.

PMID- 10944024
TI  - Scatter radiation from palladium-103 prostate seed implants on bone scan.

PMID- 10944025
TI  - Vesicocecal fistula detected during dynamic renal scintigraphy.

PMID- 10944026
TI  - Imaging of giant cell arteritis: evidence of splenic involvement using FDG
      positron emission tomography.

PMID- 10944028
TI  - Typical appearance of mesothelioma on an F-18 FDG positron emission tomograph.

PMID- 10944027
TI  - Cerebrospinal fluid rhinorrhea caused by a congenital defect of stapes mimicking
      otorrhea: radionuclide cisternographic findings.

PMID- 10944029
TI  - Tc-99m (V) dimercaptosuccinic acid scintigraphy for bone and soft tissue lesions.

PMID- 10944030
TI  - Highly vascular breast cancer detected on a Tc-99m RBC gated cardiac blood pool
      imaging study.

PMID- 10944031
TI  - Intestinal activity on Tc-99m MAG3 scintigraphy in a patient after renal
      transplant may interfere with interpretation.

PMID- 10944032
TI  - False-positive results of a gastrointestinal bleeding study caused by an ectopic
      kidney.

PMID- 10944033
TI  - Comparison of bone SPECT, magnetic resonance imaging, and computed tomography in
      the demonstration of vertebral metastases from bronchogenic carcinoma: an autopsy
      documented case.

PMID- 10944034
TI  - Current readings in nuclear medicine.

PMID- 10944035
TI  - Sonography of lacrimal glands in Sjogren syndrome.
AB  - This study evaluates the potential role of high resolution sonography and color
      Doppler sonography in the evaluation of the lacrimal glands in Sjogren syndrome.
      We examined 15 women (age range, 52-73 years) affected by Sjogren syndrome and 15
      women with no history and signs of lacrimal disease (age range, 47-75 years). The
      lacrimal glands were visualized bilaterally in 6 of 15 patients. The lacrimal
      artery was detectable in all patients; the resistive index was higher than normal
      (0.72+/-0.04). An abnormal Schirmer test was present in six of six patients with
      visible glands and in two of nine patients with invisible glands; xerophthalmia
      was present in six of six patients with visible glands and in four of nine
      patients with invisible glands; high levels of serum immunoglobulins were present
      in six of six patients with visible glands and in three of nine patients with
      invisible glands. Sonography is able to provide noninvasively much of the
      information needed by the clinician.

PMID- 10944036
TI  - Power Doppler sonography of normal cervical lymph nodes.
AB  - This study was undertaken to investigate the vascular patterns and resistance of
      normal cervical nodes by power Doppler sonography. In 101 subjects who had a
      sonographic examination of the neck, 1050 lymph nodes were detected. Only central
      vascularity was found in normal cervical nodes. The degree of vascularity in
      submental and submandibular nodes was higher than that in other regional nodes.
      Submental nodes had a higher vascular resistance in association with a lower
      blood flow velocity than other regional nodes. No significant difference was
      found in blood flow velocities and vascular resistance between male and female
      subjects. The vascular resistance increased significantly with age. This study
      provides a baseline for vascularity within normal cervical nodes, as seen by
      power Doppler sonography.

PMID- 10944037
TI  - Air-contrast sonohysterography as a first step assessment of tubal patency.
AB  - We assessed the use of air as a sonographic contrast agent in the investigation
      of tubal patency by sonohysterography. We examined 115 women assessed for
      infertility. After saline sonohysterography, small amounts of air were
      insufflated, and the tubal passage of bubbles was monitored. In five patients
      (excluded from the results), cervical stenosis prevented the procedure. Ninety
      one tubes (right side) and 86 tubes (left side) were definitively patent; 5 and
      7, respectively, were probably patent; and 12 and 16, respectively, were
      nonvisualized. Nine patients had polyps, 3 had synechiae, and 2 had submucosal
      fibroids. None of the patients had infectious complications. Air
      sonohysterography and laparoscopy with chromopertubation showed agreement in
      79.4%. In 17.2% of patients, the tubes were considered nonvisualized by air
      sonohysterography when they were patent. The sensitivity was 85.7% and
      specificity 77.2%. In conclusion, air-sonohysterography is a comfortable, simple,
      and inexpensive first line of tubal patency investigations yielding high
      accuracy.

PMID- 10944038
TI  - Adenomyosis: sonographic findings and diagnostic accuracy.
AB  - The purposes of this study were to evaluate the accuracy of pelvic sonography in
      identification of adenomyosis and to characterize the most commonly seen
      sonographic features. We identified all patients over a 10 year period in whom a
      prospective diagnosis of adenomyosis was suspected on the basis of sonographic
      findings and who had undergone hysterectomy at a single hospital. Patients were
      referred for sonography based on standard indications. Sonographic features used
      in the diagnosis of adenomyosis consisted of two or more of the following: a
      mottled inhomogeneous myometrial texture, globular appearing uterus, small cystic
      spaces within the myometrium, and a "shaggy" indistinct endometrial stripe.
      Correlation was made with the pathology report on the hysterectomy specimen.
      Fifty-one women met the study criteria. Forty-three of 51 (84.3%) patients
      sonographically suspected of having adenomyosis were confirmed as having
      adenomyosis by pathologic examination. All patients with adenomyosis had a
      mottled heterogeneous appearing uterus, 95% had a globular uterus, 82% had small
      myometrial lucent areas, and 82% had an indistinct endometrial stripe. Eight
      patients (15.6%) who had been suspected of having adenomyosis by pelvic
      sonography did not have adenomyosis reported in the pathology specimen. Six of
      these eight (75%) patients had multiple small fibroids, one had stage IV
      endometriosis, and one had a normal uterine specimen with no evidence of
      pathology. Pelvic sonography provides an accurate diagnosis of adenomyosis in the
      majority of cases.

PMID- 10944039
TI  - Safety and efficacy of sonographically guided random core biopsy for diffuse
      liver disease.
AB  - Sonographic guidance is commonly used in the biopsy of focal hepatic lesions, but
      biopsy for diffuse disease is often non-image-guided. We evaluated the safety and
      efficacy of real-time sonographically guided random core biopsy in the assessment
      of diffuse liver disease in 210 patients. The two most common indications for
      biopsy were viral hepatitis (in 113 patients) and elevated liver function test
      results of unknown cause (in 54 patients). Ultrasonography and pathology reports
      were reviewed retrospectively to determine number of needle passes and final
      diagnoses. Adequate tissue was obtained in all 210 patients, with 259 of 269
      (96%) passes having been successful. Specimens were submitted for light
      microscopy and other tests as indicated. No difference in success rates was found
      for right and left lobe biopsies. No major complications occurred. Minor
      complications occurred in 10 of 210 (4.8%) patients and were self-limited.
      Sonographically guided core liver biopsy is a safe and effective method for the
      diagnosis of liver disease.

PMID- 10944040
TI  - Diagnostic accuracy of abdominal ultrasonography compared to magnetic resonance
      imaging in siderosis of the spleen.
AB  - A prospective study to compare the diagnostic performance of ultrasonography with
      magnetic resonance imaging using gradient-recalled echo technique in cases of
      siderosis of spleen was conducted in 53 cirrhotic patients with endoscopic proof
      of gastroesophageal varices. Of the 34 patients with splenic siderosis on MR
      imaging, punctate hyperechoic foci were detected in the spleen on ultrasonography
      in 24 patients. Using MR imaging as the reference standard for the diagnosis of
      splenic siderosis, the sensitivity of ultrasonography is 70.6%; specificity is
      78.9%; positive predictive value is 85.7%; and negative predictive value is 40%.
      We conclude that ultrasonography is a fairly accurate technique in the diagnosis
      of splenic siderosis.

PMID- 10944041
TI  - Three-dimensional ultrasonographic imaging of the neonatal brain in high-risk
      neonates: preliminary study.
AB  - The aim of this investigation was to compare the utility of three-dimensional
      ultrasonography versus two-dimensional ultrasonography in imaging the neonatal
      brain. Thirty patients in the neonatal intensive care unit underwent two
      dimensional and three-dimensional ultrasonography. The resultant two- and three
      dimensional images recorded on film and three-dimensional volumes (reviewed on a
      workstation) were evaluated independently. Comparable numbers of normal and
      abnormal studies were diagnosed by each modality. Axial images were considered
      useful in approximately 50% of three-dimensional cases. Image quality, overall
      and in the far-field, was rated higher on two-dimensional images. Three
      dimensional sonographic acquisition time in the neonatal intensive care unit (1.7
      min+/-0.7 standard deviation) was significantly shorter than that for two
      dimensional sonography (9.0+/-4.5 min). The total time for evaluation on the
      three-dimensional workstation (4.4+/-1.1 min) was significantly less than that
      for two-dimensional images on film (10.6+/-4.7 min). In conclusion, three
      dimensional ultrasonography is a promising, diagnostically accurate, and
      efficient imaging tool for evaluation of the neonatal brain; however,
      visualization must improve before it can replace two-dimensional ultrasonography.

PMID- 10944042
TI  - Gray scale second harmonic imaging of acoustic emission signals improves
      detection of liver tumors in rabbits.
AB  - This study evaluates a new reticuloendothelium specific sonographic contrast
      agent NC100100 (Sonazoid) for detection of liver VX-2 tumors in rabbits. Gray
      scale imaging of five groups of three rabbits, with hepatic VX-2 tumors implanted
      7, 10, 12, 14, and 18 days previously, was performed prior to injection of
      Sonazoid (dosages, 0.01-0.5 ml/kg). Sonazoid produces induced acoustic emission
      after uptake in the liver. Therefore, harmonic gray scale images were obtained
      immediately after injection as well as delayed (by up to 2(1/2) h). Five rabbits
      (one from each group) also had angiography performed, while all animals were
      evaluated by pathologic examination. Non-contrast enhanced sonography detected 17
      of 61 tumors (29%), as well as three false-positives, while the addition of
      Sonazoid detected 57 tumors (93%) and one false-positive (P<0.001). Acoustic
      emission made 2 x 2 mm tumors (invisible in conventional B-mode sonography)
      clearly perceivable in harmonic gray scale. In the subgroup that received
      angiography, 12 of 36 tumors (33%) were detected with conventional sonography
      compared to 22 tumors (61%) seen with angiography (P = 0.002). After injection of
      Sonazoid the ultrasonographic detection rate increased to 97% (35 of 36 tumors),
      which was a significant improvement over angiography (P = 0.00024). Improved
      detection of hepatic VX-2 tumors with second harmonic gray scale imaging of
      Sonazoid is possible because of this agent's acoustic emission capabilities.

PMID- 10944043
TI  - Second trimester ultrasonography may identify 77 to 97% of fetuses with trisomy
      18.
AB  - Between 1990 and 1999, 30 second trimester fetuses with trisomy 18 and 2000
      control fetuses underwent real-time and color Doppler ultrasonographic
      examination followed by genetic amniocentesis. Abnormal fetal anatomy was present
      in 97% of fetuses with trisomy 18, with a false-positive rate of 15.7%. Logistic
      regression identified six markers (choroid plexus cysts, central nervous system
      malformations, an abnormal nuchal skin fold, ventricular septal defect, outflow
      tract abnormalities of the heart, and right-to-left chamber disproportion of the
      heart) and one interaction between markers (right-to-left chamber disproportion
      and outflow tract abnormalities) to significantly contribute to the
      identification of 93% of fetuses with trisomy 18, with a false-positive rate of
      8.9%. Noncardiovascular markers (choroid plexus cysts, central nervous system
      malformations, and abnormal nuchal skin fold) identified 77% of fetuses with
      trisomy 18, with a false-positive rate of 3.9%. Combining right-to-left chamber
      disproportion of the heart with choroid plexus cysts, central nervous system
      malformations, and nuchal skin folds identified 83% of fetuses with trisomy 18,
      with a false-positive rate of 4.4%.

PMID- 10944044
TI  - Color Doppler sonographic study of the uterine artery in patients using
      intrauterine contraceptive devices.
AB  - A transvaginal Doppler sonographic examination of uterine artery blood flow was
      performed. Resistance and pulsatility indices were measured in 101 women, 74 of
      whom were using an intrauterine contraceptive device, and 27 controls, who were
      not using any contraceptive method. The intrauterine contraceptive device users
      were divided into three groups: those with normal bleeding (n = 34); those with
      abnormal uterine bleeding without medication (n = 16); and those with abnormal
      bleeding corrected with use of prostaglandin inhibitors (n = 24). The resistance
      and pulsatility values were significantly lower in the group of women using
      intrauterine contraceptive devices who had abnormal bleeding than in all other
      groups (P<0.001). All other comparisons were nonsignificant. A pulsatility index
      of less than 2 may be associated with a higher risk for development of
      intrauterine contraceptive device-induced bleeding.

PMID- 10944045
TI  - Clinical significance of placenta previa detected at early routine transvaginal
      scan.
AB  - Transvaginal ultrasonography in early pregnancy was used to determine the
      prevalence of placenta previa and the rate of persistence until delivery. The
      location of the placenta was registered systematically in 2342 pregnant women who
      underwent transvaginal ultrasonography at 10 to 16 weeks' gestation as a primary
      examination. The outcome of pregnancy as well as the presence or absence of
      placenta previa at delivery was noted in a total of 2158 cases. A receiver
      operating characteristic curve was generated for the different measurements from
      the edge of the placenta to the internal cervical os versus placenta previa at
      delivery. In 105 of the 2158 women screened in the early stages of pregnancy
      (4.9%) the placenta extended to or over the internal cervical os, and in 34 of
      2158 patients (1.6%) the distance to the placental edge beyond the internal
      cervical os was equal to or greater than 14 mm. Of the eight cases of placenta
      previa at delivery, six (75%) were identified in our study, and two cases were
      missed. When a cutoff value of greater than 14 mm is used for the receiver
      operating characteristic curve the likelihood is 17.6% (95% confidence interval =
      6.8 to 34.5) for placenta previa at delivery. Although a high percentage of false
      positive results occur owing to the low prevalence at delivery, this screening
      procedure can identify high-risk patients who should be rescanned later in
      pregnancy.

PMID- 10944046
TI  - Correlation of central venous pressure with Doppler waveform of the common
      femoral veins.
AB  - The objects of this prospective study were to determine the nature of the flow in
      the right femoral vein and to correlate the flow velocity with the venous
      pressure measured in the right atrium. We performed 236 pulsed Doppler
      ultrasonographic examinations in 1 year on patients with a venous catheter with
      the distal tip in the right atrium. In the Doppler wave readouts we analyzed wave
      frequency, velocity components, and relationships among them and the existence of
      pulsatile flow. These parameters were then compared to the right atrium pressure.
      We investigated the correlation between the atrium pressure and the flow velocity
      obtained from the Doppler waveforms of the common femoral veins, obtaining a
      significant correlation (P<0.0001) with the following: the atrium systolic wave
      a, the atrium diastolic wave v, the pulsatility ratio (PR = Vmin/Vmax) and the
      pulsatility index (PI = [Vmax - Vmin] /Vavg). The receiver operating
      characteristic showed that the pulsed Doppler ultrasonography is not a sensitive
      technique in diagnosis high atrium pressures. In addition, both cardiac and
      respiratory phasicity of the venous wave was observed. A significant inverse
      relation was found between the pulsatile flow and high atrium pressure.
      Nonetheless, the low sensitivity of this technique does not allow the use of
      pulsatile Doppler ultrasonography in the common femoral vein for diagnosing
      increases of the atrium pressure.

PMID- 10944048
TI  - The aetiology of otitis media with effusion: a review.
AB  - Otitis media with effusion (OME) is the most common cause of deafness in children
      in the developed world. In this article we aim to present an overview of current
      research developments on the aetiology of OME and the resulting implications for
      treatment. In the model we describe, the primary event is inflammation of the
      middle ear mucosa, usually due to the presence of bacteria. This leads to the
      release of inflammatory mediators, which cause secretion of a mucin-rich effusion
      by up-regulating mucin genes. Prolonged stimulation of the inflammatory response
      and poor mucociliary clearance lead to persistence of the middle ear fluid,
      giving rise to the clinical presentation of OME. We describe OME in the following
      sequence: the initial production of the effusion, the composition of the effusion
      produced, and factors impairing clearance of the effusion.

PMID- 10944047
TI  - Angiogenesis in head and neck squamous cell carcinoma.
AB  - Tumour angiogenesis has recently attracted a great deal of attention as a
      critical part of oncogenesis and a necessary prerequisite for a malignant
      phenotype. Research into this process not only offers new insights into tumour
      biology but is also leading to the development of realistic novel and minimally
      toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines
      and pathways have been characterized and their interrelationships are becoming
      increasingly complex as new findings are made. This article reviews the current
      understanding of tumour angiogenesis, the basic mechanisms involved and the more
      important and investigated pathways and proteins involved.

PMID- 10944049
TI  - Cognitive dissonance, the placebo effect and the evaluation of surgical results.

PMID- 10944050
TI  - The use of diagnostic sleep nasendoscopy in the management of children with
      complex upper airway obstruction.
AB  - In this paper we present a prospective study of the role of diagnostic sleep
      nasendoscopy in the investigation and treatment of 20 children referred to a
      tertiary children's hospital with obstructive awake apnoea or severe obstructive
      sleep apnoea (apnoea/hypopnoea index greater than 30/h). We describe the
      technique of diagnostic sleep nasendoscopy and provide a classification system
      for documenting the findings. We demonstrate sleep nasendoscopy is an invaluable
      tool in the management of children who continue to have upper airway obstruction
      despite previous adenotonsillectomy and in children with airway obstruction due
      to cerebral palsy, syndromes and craniofacial malformations. With the use of pre-
      and post-intervention sleep studies we have shown that sleep nasendoscopy is
      accurate in deciding the most appropriate mode of intervention in the individual
      child with obstructive breathing, from (continuous positive airway pressure) CPAP
      to site-specific surgery. We conclude that sleep nasendoscopy combined with rigid
      laryngo-bronchoscopy should be standard practice in the evaluation of children
      with complex upper airway obstruction.

PMID- 10944051
TI  - Randomised controlled trial of early surgery versus watchful waiting for glue
      ear: the effect on behavioural problems in pre-school children.
AB  - This trial was designed to compare early surgery with watchful waiting for
      persistent bilateral otitis media with effusion (OME) in terms of hearing loss
      and behavioural problems in pre-school children. A randomised controlled trial
      compared the effects of early treatment with ventilation tubes versus watchful
      waiting for 9 months. Results were analysed by intention-to-treat. One hundred
      and eighty-two pre-school children (date of birth between 1 April 1991 and 31
      December 1992), mean age of 2.9 years (SD 0.85) with at least a 3-month history
      of bilateral OME and hearing loss of greater than 25 dB were treated in Bristol
      Children's Hospital between November 1993 and January 1996. Bilateral ventilation
      tubes were inserted within 6 weeks of randomisation or within 6 weeks of
      reassessment after 9 months of watchful waiting, with a final assessment at 18
      months. The main outcome measures were behavioural problems, measured by the
      Richman Behaviour Checklist, and hearing loss at 4000 Hz in the better hearing
      ear. Early surgical intervention significantly reduced behavioural problems by
      17% (95% CI, 2% - 33%). This difference was largely mediated by concurrent
      hearing loss. After 18 months, there was no longer a significant difference (95%
      Cl, -19% to +10%). However, the majority (85%) of the Watchful Waiting group had
      required surgery and 22% of all children still had behavioural problems.

PMID- 10944052
TI  - Does waiting time for radiotherapy affect local control of T1N0M0 glottic
      laryngeal carcinoma?
AB  - This is a retrospective study of 362 patients with a T1N0M0 glottic laryngeal
      carcinoma treated by radiotherapy. Waiting time was defined as time from the day
      of histopathological diagnosis to the first day of radiotherapy. The Cox
      regression model was used to analyse the influence of waiting time for
      radiotherapy on the incidence of recurrence. The median follow-up time was 4.4
      years. The median waiting time for radiotherapy was 43 days. Local recurrences
      were found in 58 patients. There was no significant correlation (P= 0.88) between
      waiting time and the outcome of early glottic cancer as analysed by Cox
      regression. This retrospective study did not demonstrate an effect of waiting
      time for radiotherapy on the outcome of early glottic laryngeal cancer.

PMID- 10944053
TI  - Hypoglossal-facial nerve anastomosis: assessment of clinical results and patient
      benefit for facial nerve palsy following acoustic neuroma excision.
AB  - Despite advances in neuro-otological techniques permanent complete facial palsy
      may still occur in up to 10% of patients undergoing removal of cerebellopontine
      angle tumours. Hypoglossal-facial nerve anastomosis is the procedure of choice in
      our unit for facial reanimation in such patients and below we report the results
      of hypoglossal-facial nerve anastomosis performed on 29 patients. Assessment of
      patient benefit from hypoglossal-facial nerve anastomosis was obtained using a
      questionnaire based on the Glasgow Benefit Inventory. The results showed all
      patients to have an improvement in their House Brackmann grade following
      hypoglossal-facial anastomosis with 65% achieving grade III or better. Of the 20
      patients who completed the questionnaire, 18 showed a positive benefit (median
      score 59.5, range 40-77). There was a significant correlation (P < 0.045) between
      the Glasgow benefit inventory score and House Brackmann grade. Outcome was not
      affected by the time interval between the acoustic neuroma surgery and performing
      the hypoglossal-facial nerve anastomosis, sex or length of follow-up. However the
      Glasgow benefit score was significantly influenced by age (P = 0.023) with
      younger patients showing more benefit independent of improvement in facial nerve
      function.

PMID- 10944054
TI  - Clinical applicability of the Ljubljana classification of epithelial hyperplastic
      laryngeal lesions.
AB  - The diagnosis, prognosis, and choice of treatment of various laryngeal lesions
      depends almost entirely on the interpretation of changes in the covering
      epithelium. These abnormalities, referred to as epithelial hyperplastic laryngeal
      lesions, have been graded according to the Ljubljana classification into simple,
      abnormal and atypical (risky epithelium) hyperplasia and carcinoma in situ. The
      aim of this study was to evaluate the clinical applicability and prognostic value
      of this classification and to determine the incidence of malignant
      transformation. A retrospective clinical-pathological analysis was performed in a
      series of 4167 patients with 4574 biopsies, treated from 1979 to 1994. Simple
      (benign prickle cell) hyperplasia was the predominant grade in nodules, polyps,
      Reinke's oedema, granulomas, and papillomas, accounting for 37.6-68.6% of cases.
      In chronic laryngitis, abnormal (benign basal cell) hyperplasia was predominant
      with 43.9% of cases. Atypical ('risky') hyperplasia was observed almost
      exclusively in patients with chronic laryngitis (16.1%) and papillomas (10.1%),
      and only exceptionally in patients with vocal cord nodules (0.9%) and Reinke's
      oedema (0.3%). The percentage of malignant transformation in atypical hyperplasia
      was 11.6% (13/112 patients in 2-12 years), while in simple and abnormal
      hyperplasia, it was 0.3% (8/2920 patients in 1.5-11 years). The data support the
      concept of the Ljubljana classification dividing epithelial hyperplastic
      laryngeal lesions into benign (simple and abnormal hyperplasia), potentially
      malignant (atypical hyperplasia) lesions and carcinoma in situ.

PMID- 10944056
TI  - The laryngeal mask airway in tonsillectomy: the surgeon's perspective.

PMID- 10944055
TI  - Nitinol stents: their value in tracheobronchial obstruction.
AB  - Recurrent tracheobronchial obstruction whether due to a benign or malignant cause
      is not always amenable to surgery and one is left with the dilemma of what to do
      for a patient who is slowly asphyxiating. Various modalities have been employed
      in the past with varying degrees of success. However due to the recent
      innovations in 'superelastic' biocompatible alloys we present our clinical
      experience with a new generation of metallic stents made from Nitinol. Over a 12
      month period we inserted eight stents in six patients with malignant and benign
      tracheobronchial obstruction. Almost all patients had dramatic improvement in
      their symptoms and there was little airway reaction observed up to 18 months
      after insertion. However, one should exercise caution in inserting them for
      benign conditions as we regard them as permanent implants. Also evident is the
      inherent morbidity in this group of patients and this needs to be carefully
      considered prior to treatment.

PMID- 10944057
TI  - The writing on the web?

PMID- 10944058
TI  - Report from University of Oxford.

PMID- 10944059
TI  - Reforming primary care in England--again. Plans for improving the quality of
      care.
AB  - An extensive programme of health service reform has begun in England. Improvement
      in the quality of care is a key objective of the reforms, and several initiatives
      are being introduced in response. These include systems to provide national
      guidance about appropriate treatment and services, a local system to support
      quality improvement and arrangements to monitor performance, including a new
      performance framework, an inspection agency and an annual survey of patients. The
      local quality improvement system has features of particular interest. These
      include arrangements for setting objectives for quality improvement, the use of
      various quality improvement methods tailored to local needs and a new system to
      provide accountability to both the health service and the public. The
      introduction of clinical governance and all the other reforms presents primary
      care practitioners with a major challenge. However, if sufficient time is allowed
      and adequate resources are made available, the reforms do have the potential to
      improve health care in England.

PMID- 10944060
TI  - Out-of-hours service in rural areas. An observational study of accessibility,
      attitudes and quality standards among general practitioners in Iceland.
AB  - OBJECTIVES: To examine the access, workload, duties, commitments and quality
      standards of primary care physicians (GPs) resulting from out-of-hours service.
      SETTING: All GPs (n = 96) in rural Iceland. MAIN OUTCOME MEASURES: Answers to a
      postal survey. RESULTS: The participation rate was 80%. The GPs estimated that in
      97% of the cases they could be contacted within 5 minutes in an emergency. Under
      usual circumstances (weather conditions) and within a distance of 10 km, 70% of
      them could reach the patient within 30 minutes of receiving the call. In severe
      weather conditions, 50% of the GPs in smaller districts (650-6000 inhabitants)
      estimated that it could take up to 5 hours or more to reach the patient (which
      could happen once a year). In the least populated districts, 84% of the GPs had
      to be on call 14 days or more per month. Serious emergencies (involving special
      training such as cardiac resuscitation or tracheal intubation) were relatively
      rare, and GPs expressed the necessity for regular refresher courses in such
      fields. CONCLUSIONS: Modern telecommunication networks guarantee good access to
      out-of-hours service. The workload and on-call duties are great and do not comply
      with European Union (EU) recommendations regarding minimal rest time. If GPs in
      rural areas are to be expected to provide frontline health care, including in
      severe emergency situations, regular training courses are needed.

PMID- 10944061
TI  - Sick-listing habits among general practitioners in a Swedish county.
AB  - OBJECTIVE: To describe sick-listing habits in general practice, how common it is
      and for how long and for what diagnoses it is granted. DESIGN: Medical audit
      study. SETTING: Primary health care. SUBJECTS: 53 general practitioners (GPs)
      registering all cases during a 2-week period when sick-listing was considered.
      MAIN OUTCOME MEASURES: Percentage of GP consultations that involved sick-listing,
      number of days of certified sick-leave, percentage of partial sick-listing, GP
      sex differences. RESULTS: 9% of all consultations included a consideration about
      sick-listing, and in only 6% of these instances was a certificate not issued. The
      median length of the certified sickness period was 14 days. Musculoskeletal
      problems were by far the most common diagnosis. Female patients were more often
      partially sick-listed than males. Female GPs sick-listed a larger proportion of
      their patients than male GPs. Risk factors for long certification periods were in
      fact associated with long certification periods. Even in cases where the GP would
      not recommend sick-listing a certificate was issued in 87%. CONCLUSIONS: Patients
      appear to have a strong influence on sick-listing practice, and there are
      important sex differences among GPs in this practice.

PMID- 10944063
TI  - Wide variation in the number of different drugs prescribed by general
      practitioners. A prescription database study.
AB  - OBJECTIVES: To investigate the number of different drugs prescribed per
      dispensing unit and to analyse the influence of practice characteristics on this
      number. DESIGN: Register analysis based on the Odense Pharmacoepidemiological
      Database (OPED). SETTING: General practices in the County of Funen, Demnark.
      SUBJECTS: 173 general practices (99 single-handed and 74 group practices). MAIN
      OUTCOME MEASURES: Number of different drugs prescribed per dispensing unit.
      RESULTS: The number of different drugs prescribed per dispensing unit varied
      nearly fourfold (range 102-381) and four practice characteristics were able to
      predict 74% of this variation. Practices with several doctors, a high number of
      patients listed per doctor, a high percentage of elderly individuals, and a heavy
      workload showed the highest number of different drugs prescribed. CONCLUSION: As
      the quality of drug prescribing is associated with the use of a limited number of
      drugs, it is suggested that GPs should agree on a formulary containing the most
      essential drugs in primary health care.

PMID- 10944062
TI  - Factors influencing GPs' decisions on the treatment of hypercholesterolaemic
      patients.
AB  - OBJECTIVE: To study factors influencing GPs' decisions to prescribe lipid
      lowering drugs and how their judgements agree with the Swedish guidelines on
      hyperlipidaemia. DESIGN: Postal questionnaire. SETTING: Primary health care.
      Authentic written case descriptions of patients, all with a cholesterol value of
      at least 5.5 mmol/l and with variations in seven other variables (cues) in a
      Clinical Judgement Analysis (CJA) design. SUBJECTS: Sixty randomly selected
      primary health care doctors in the south-eastern Stockholm area. RESULTS: Thirty
      eight doctors answered the questionnaire. Coronary heart disease had the highest
      influence on judgements, followed by cholesterol. The majority of doctors used
      two or three of the eight cues. Doctors differed markedly in their strategies.
      One in four did not use coronary heart disease in their judgements, even though
      all patients with this risk factor present (12/40) should receive pharmacological
      treatment, according to the guidelines. Doctors who adhered to the guidelines in
      this respect were younger than those who did not. The GPs' insights into their
      own strategies were good. CONCLUSIONS: The results indicate that doctors use very
      different judgement strategies for drug prescription concerning patients with
      hypercholesterolaemia. A fairly large subgroup of the doctors did not include
      coronary heart disease in their judgements, in contrast to the present
      guidelines.

PMID- 10944064
TI  - GPs' ability to diagnose dyspepsia based only on physical examination and patient
      history.
AB  - OBJECTIVES: To evaluate the diagnostic value of the general practitioner's (GP's)
      unaided working diagnoses in dyspepsia. To compare the proportions of final
      diagnoses and the characteristics of patients who would have been referred to
      gastroscopy or to empirical drug treatment. DESIGN: Clinical study. PATIENTS: 400
      consecutive dyspeptic patients consulting their GPs. MAIN OUTCOME MEASURES:
      Sensitivity, specificity and positive and negative predictive values (PV+ and PV
      ) were calculated for the GP's working diagnoses in cases of dyspepsia. The
      outcome of his/her decisions on how to manage dyspeptic patients was also
      evaluated. RESULTS: Gastroesophageal reflux disease would have been diagnosed
      accurately, with a sensitivity of 0.59, specificity 0.83, PV+ 0.43 and PV- 0.90.
      GPs diagnosed functional disorders with a sensitivity of 0.43, specificity 0.69,
      PV+ 0.56 and PV- 0.54; peptic ulcer with a sensitivity of 0.37, specificity 0.83,
      PV+ 0.28 and PV- 0.88; and malignancy with a sensitivity of 0.13, specificity
      0.97, PV+ 0.08 and PV- 0.98. Patients who would have been referred to gastroscopy
      had more often lost weight (p = 0.01), suffered from abdominal pain (p=0.03) and
      from symptoms partly suggesting irritable bowel syndrome (p< or =0.03).
      CONCLUSIONS: The clinical diagnosis of the causes of dyspepsia is unreliable. In
      selecting patients for gastroscopy, more attention should be paid to risk factors
      such as age, use of non-steroidal anti-inflammatory drugs and history of previous
      peptic ulcer.

PMID- 10944065
TI  - Endomysium antibodies are superior to gliadin antibodies in screening for coeliac
      disease in patients presenting supposed functional gastrointestinal symptoms.
AB  - OBJECTIVE: To study the accuracy of IgA- and IgC-gluten antibodies and endomysium
      antibodies as screening tools for endoscopy with small bowel biopsy for
      histologic diagnosing of coeliac disease. DESIGN: Comparing serology with
      histologic examination--the "gold standard" for diagnosing coeliac disease.
      SETTINGS: 1. The municipality of Osthammar, Sweden. 2. The catchment area of the
      University Hospital, Uppsala, Sweden. PATIENTS: 1. A random subsample (50 with
      dyspepsia, 50 with irritable bowel syndrome and 50 symptomless) of a
      representative sample from an adult Swedish general population (20-80 years; n =
      1260). 2. All patients with a diagnosis of coeliac disease admitted to the
      University Hospital in Uppsala, Sweden during the course of 10 months. MAIN
      OUTCOME MEASURES: The accuracy of IgA- and IgG-gluten antibodies and endomysium
      antibodies. RESULTS: There were no significant correlations between IgA-gluten
      antibodies and IgG-gluten antibodies, on the one hand, and symptoms or symptom
      severity, on the other. Using duodenal biopsy results as the gold standard, IgA
      gluten antibodies had a low specificity and IgG-gluten antibodies a low
      sensitivity, whereas endomysium antibodies had an excellent accuracy. CONCLUSION:
      Endomysium antibodies seem to be the screening test of choice. The load of
      diagnostic upper endoscopies would be considerably decreased compared to using
      gluten antibodies.

PMID- 10944066
TI  - Relations between Helicobacter pylori, thyroid disease and cardiovascular risk
      factors in a 56-65-year-old population.
AB  - OBJECTIVE: To estimate the prevalence of and relation between Helicobacter pylori
      (HP) and thyroid disease in a 56-65-year-old population with cardiovascular risk
      factors. DESIGN: Cross-sectional study including every second individual in the
      age group. SETTING: The primary health care district of Molnlycke, with about
      14,000 inhabitants. PATIENTS: 170 men and 217 women aged between 56 and 65 years.
      MAIN OUTCOME MEASURES: Anthropometric (body mass index (BMI), waist/hip ratio
      (WHR)) and blood pressure measurements, biochemical analyses, including s-TSH, s
      FT4 and HP serology. RESULTS: There was a high prevalence of metabolic risk
      factors in this pre-retirement group of individuals. The prevalence of HP was 42%
      in both men and women. Only a significant correlation between HP and WHR was seen
      in men. CONCLUSIONS: No reason could be found for including analysis of HP and
      thyroid tests in screening programmes for cardiovascular risk factors in men and
      women.

PMID- 10944067
TI  - Smokers over age 35 continue to receive oral contraceptives. Survey of patients
      in a family practice residency practice.
AB  - OBJECTIVE: To assess the frequency with which women over age 35 report both
      current oral contraceptive use and current cigarette smoking. DESIGN: Cross
      sectional survey of women in a single practice setting. SETTING: Primary care
      teaching practice in a mid-sized US city. PATIENTS: 142 women aged 35-55 who had
      not reached menopause and had not had hysterectomy. MAIN OUTCOME MEASURES:
      Smoking status in current oral contraceptive users. RESULTS: 19 women (13%) were
      current oral contraceptive users and 46 (32%) were current smokers. Four of the
      oral contraceptive users (21%) reported current smoking. CONCLUSIONS: Despite
      reported cardiovascular risk, women who smoke continue to receive prescriptions
      for oral contraceptives. Physicians should redouble efforts to record smoking
      status and offer smoking cessation treatment to women over age 35 who smoke and
      wish to take oral contraceptives.

PMID- 10944068
TI  - Quality of life and hormone therapy in women before and after menopause.
AB  - OBJECTIVE: To study how women evaluate their quality of life (QoL) in relation to
      age, menopause and hormone therapy (HT). DESIGN: An anonymous postal
      questionnaire comprising the Gothenburg QoL Instrument and items concerning
      menopause, symptoms, diseases, drugs and smoking. SETTING: A primary care
      district in southern Sweden. SUBJECTS: All women aged 45, 50, 55 and 60 in 1995
      (n = 126), 1996 (n = 130), 1997 (n = 134) and 1998 (n = 145). MAIN OUTCOME
      MEASURES: QoL (global, social, physical/mental well-being) and number of symptoms
      (psychological, physical) reported during the past 3 months. RESULTS: The older
      women rated their QoL, especially social well-being (p < 0.001), higher and
      reported a lower number of symptoms, particularly psychological symptoms (p =
      0.02), than the younger women did. Pre- and post-menopausal women in the various
      age groups did not differ on the main outcome measures. A history of HT and use
      of hormonal contraceptives tended to be associated with lower well-being and a
      greater number of symptoms, an association found in women 55 years of age to be
      highly significant (p < 0.01-0.001) for all the main outcome measures.
      CONCLUSION: The effects of menopause on QoL seemed generally to be of minor
      importance. QoL in women was lower in those with a history of HT than in those
      with no such experience.

PMID- 10944069
TI  - The wheezing schoolchild--an undiagnosed asthmatic. A follow-up of children with
      parentally reported episodes of wheeze without diagnosed asthma.
AB  - OBJECTIVE: To examine children aged 7-15 years with parentally reported episodes
      of wheeze in order to estimate the proportion of undiagnosed asthmatics in this
      group. DESIGN: A cross-sectional study with clinical examination of subgroups.
      SETTING: All children (n = 832) aged 7-15 years in the municipality of Odda.
      SUBJECT: Based on completed questionnaires, the children were selected to one of
      four groups: Children with wheeze but no asthma (wheeze group); children with
      current asthma (asthma group); children with past asthma (past asthma group); and
      children with neither asthma nor wheeze (control group). MAIN OUTCOME MEASURES:
      Parental reports of episodes of wheeze, assessment of skin prick test
      sensitivity, measures of lung function and exercise-induced bronchoconstriction
      (EIB). RESULTS: In the wheeze group, 3 (7.5%) of 40 children were diagnosed with
      asthma in the 18-month period between the questionnaire survey and the
      examination, while 4 (10%) other children had EIB. Another 8 children (20%)
      reported 3 episodes of wheeze or more, and at least 1 episode during the 12-month
      period before the clinical examination. Classifying these children as asthmatics
      would give a proportion of 37.5% with undiagnosed asthma in the wheeze group, and
      the prevalence of current asthma among children aged 7-15 would rise from 2.9%
      based on a questionnaire survey to 4.9%. CONCLOSIONS: Using a wide definition of
      asthma, this study suggests that a large proportion of Norwegian children with
      wheeze actually have asthma.

PMID- 10944070
TI  - Side effects of beta-blocker treatment for hypertension.

PMID- 10944072
TI  - Comparative uptake, bioaccumulation, and gill damages of inorganic mercury in
      tropical and nordic freshwater fish.
AB  - This paper reports comparative results on the bioaccumulation of inorganic
      mercury and resulting gill damages in the tropical fish, Trichomycterus zonatus,
      and a nordic species, Salvelinus alpinus, using radioisotope 203Hg techniques and
      scanning electron microscopy. Uptake of inorganic Hg from water was much more
      important in T. zonatus than in S. alpinus and the Hg concentration in S. alpinus
      increased at a slower rate in all tissues during the first 24 h of exposure.
      After 96 h, Hg concentration was 70 times higher in the kidney, 10 times higher
      in liver, intestine, skin, and brain, and 3 times higher in gills, muscle, and
      the rest of body of T. zonatus compared to S. alpinus. Gill damages in T. zonatus
      were more evident and occurred much earlier than for S. alpinus. According to our
      data, the high differences observed in the inorganic mercury uptake,
      bioaccumulation, and gills damages strongly suggest that T. zonatus is more
      sensitive to inorganic mercury pollution than S. alpinus. Further studies are
      urgently needed to determine whether the high sensitivity observed for T. zonatus
      to inorganic Hg is also present in the majority of tropical species or whether
      this species presents an isolated case.

PMID- 10944071
TI  - Twenty-seven years studying the human neurotoxicity of methylmercury exposure.
AB  - Research at the University of Rochester (U of R) has been focused on mercury for
      nearly half a century. Initially studies focused on dosimetry, especially the
      accuracy of measuring exposure, and experimental work with animal models.
      Clinical studies in human populations started when the U of R mercury group was
      asked to assist with dosimetry in the Iraq epidemic of 1971-1972. Initial
      clinical studies described the effects of methylmercury (MeHg) poisoning on
      adults and children. A dose-response curve for prenatal exposure was determined
      and it suggested that relatively low exposures might be harmful to the fetus.
      Since most human exposure to MeHg is dietary from fish consumption, these
      theoretical dangers had far-reaching implications. After Iraq, the Rochester team
      pursued exposure from fish consumption in both adults and children. Populations
      with high fish consumption were identified in Samoa and Peru for studying adults
      and in Peru and the Seychelles islands for studying children. The possible health
      threat to the fetus from maternal fish consumption quickly became the focus of
      research efforts. This paper reviews the Rochester experience in studying human
      exposure to MeHg from fish consumption.

PMID- 10944073
TI  - PCDDs, PCDFs, PCBs, and other organochlorine compounds in human milk from Rio de
      Janeiro, Brazil.
AB  - The levels of polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs),
      polychlorinated biphenyls (PCBs), and other organochlorine compounds were
      determined in a pooled sample of breast milk from 40 mothers (first lactation:
      33; second lactation: 7, age: 15-38 years) living in the urban area of Rio de
      Janeiro County, Brazil, in 1992. Mothers were breastfeeding only one infant and
      milk was collected between 4 and 6 weeks after delivery. The results showed a
      dioxin equivalent concentration of 8.1 pg I-TEq/g milk fat. The levels of other
      chlorinated compounds (micrograms per gram of milk fat) were as follows: PCBs
      (total), 0.15; alpha-HCH, 0.001; beta-HCH, 0.27;gamma-HCH, 0.005; HCB, 0.012; DDT
      (total), 1.7; dieldrin, 0.023, and cis-heptachlor epoxide, 0.008. These results
      suggest that human background contamination by PCDD/Fs, PCBs, and HCB in Rio de
      Janeiro is lower than that generally found in industrialized countries.

PMID- 10944074
TI  - Risk concerns, land use, stewardship, and the Idaho National Engineering and
      Environmental Laboratory: attitudes of the Shoshone-Bannock and other American
      Indians.
AB  - This paper examines the attitudes and perceptions of 277 American Indians about
      hunting and fishing, risk, and future land use of the Idaho National Engineering
      and Environmental Laboratory (INEEL) in southeastern Idaho. Nearly half of our
      sample were Shoshone-Bannock tribal members living on the nearby Fort Hall
      Reservation, and half were American Indians from elsewhere in the western United
      States. We also interviewed an additional 44 White people. We examine the
      hypothesis that there are differences in environmental concerns and attitudes
      toward future land use at IN-EEL as a function of tribal affiliation (ethnicity),
      educational level, gender, and age. Such perceptions are important because of the
      existence of tribal treaties that govern the legal and cultural rights of the
      Shoshone-Bannock. Returning INEEL to the Shoshone-Bannock Tribes, hunting,
      fishing, camping, hiking, and a National Environmental Research Park ranked as
      the highest preferred future land uses, whereas continuing nuclear materials
      reprocessing and increasing the storage of nuclear wastes ranked as the lowest.
      There were tribal differences in land use preferences, with those of the Fort
      Hall Indians being more similar to those of the local Whites than to other
      American Indians. All groups ranked storage of nuclear material, storage of
      additional nuclear material, and spills and accidents as the most serious of a
      list of concerns provided about the site. Fort Hall Indians answered an open
      ended question with concerns for population levels and migration routes of game
      animals and other wildlife, more than hunting and human health. The Shoshone
      Bannock from Fort Hall showed an environmental sensitivity for the well-being of
      wildlife and the health of the ecosystem and were interested in long-term
      stewardship, in addition to 29 concern for human health.

PMID- 10944076
TI  - Exposure of preschoolers to lead in the Makati area of Metro Manila, the
      Philippines.
AB  - A study was conducted in the Makati area of Metro Manila, the Philippines. The
      study evaluated the significance of playground soil lead intake to the total
      daily lead burden in preschool children. The lead concentration was measured in
      residential playground soils, food, water, and hair samples by atomic absorption
      spectrometer and the data were used to draw conclusions. All of the playground
      soils were contaminated with lead levels ranging from a minimum of 34.54 microg/g
      to a maximum of 283.13 microg/g in comparison to the naturally occurring lead
      level of 15 microg/g in soils. Further, the study conducted a lead analysis on
      the hair of the study population to determine the accumulated lead intake.
      Ingestion of 25 mg/day of soil contributed to 4% of the total lead intake per day
      by children exposed to the study sites. Food (83%) was found to be the major
      source of lead compared to other sources. The study also includes economic
      valuation and cost benefit analysis from reducing lead in gasoline.

PMID- 10944075
TI  - Evaluation of genotoxic and cytotoxic properties of pesticides employed in
      Italian agricultural practices.
AB  - In a program coordinated by the Italian Ministry of Works, we tested in vitro
      four pesticides widely employed in a developed agricultural region of central
      Italy. The four commercial agents were chosen on the basis of their diffusion in
      agricultural practice, knowledge of their active principle(s), and scant
      availability of data concerning their toxic and genotoxic activity. The agents
      were Cirtoxin, Decis, Tramat Combi (TC), and Lasso Micromix (LM). All substances
      were tested in three in vitro systems: Chinese hamster ovary (CHO) cells, a
      metabolically competent hamster cell line (Chinese hamster epithelial liver;
      CHEL), and root tips of Vicia faba (VF). The cytotoxic and genotoxic end points
      challenged were micronuclei and root tip length (RTL) in VF and mitotic index
      (MI), proliferation index (PI), cell survival (CS), cell growth (CG), cell cycle
      length (CCL), sister chromatid exchanges, chromosomal aberrations, and single
      cell gel electrophoresis, or comet assay, in CHEL and CHO cells. Tested doses
      ranged from the field dose up to 200x the field dose to take into account
      accumulation effects. On the whole, tested agents appear to induce genotoxic
      damage only at subtoxic or toxic doses, indicating a low clastogenic risk. MI,
      PI, CS, CG, RTL, and CCL appear to be the less sensitive end points, showing no
      effects in the presence of a clear positive response in some or all of the other
      tests. Using cytogenetic tests, we obtained positive results for TC and LM
      treatments in CHO but not in CHEL cells. These data could be accounted for by
      postulating a detoxifying activity exerted by this cell line. However,
      cytogenetic end points appear to be more sensitive than those referring to
      cytotoxicity.

PMID- 10944077
TI  - Environmental fluoride content in Tibet.
AB  - As the first report of the environmental fluoride level in Tibet, the
      determination by the fluoride ion-selective electrode method of fluoride
      concentration in water, soil, fuel, grains, food, vegetables, and tea was made
      for the Tibetan people living on various land types with various ecological
      characteristics. The average level of fluoride concentration in water in Tibet
      was 0.06 mg/L; the level of dissolved fluoride in the soil was 0.45 mg/kg; the
      fluoride concentration in main fuels was 0.10 mg/kg; the levels in main grains,
      food, and vegetables were 0.06-0.33 mg/kg; those in buttered tea and Zanba mixed
      with brick tea were 3.09-3.61 mg/kg; and water-dissolved fluoride concentrations
      in the brick tea produced in Sichuan Province and Yunan Province were 533.89
      617.32 mg/kg. Tibet is the prevailing area of brick tea fluorosis.

PMID- 10944078
TI  - A community-based assessment of heat-related morbidity in North Philadelphia.
AB  - A 6-month community-based study designed to (1) determine the perceptions and
      barriers affecting the overall quality of life of isolated older adults greater
      than 65 years of age, (2) assess their risk factors, health attitudes, and
      beliefs concerning their susceptibility to heat-related conditions, and (3)
      evaluate the effectiveness of an age-specific innovative intervention program
      consisting of a specially marked clock-like thermometer and other creative
      educational materials was conducted among 34 participants during the spring and
      summer of 1997 in north Philadelphia. The study objectives were measured at
      preintervention (baseline) and at 8 weeks postintervention follow-up using a 24
      item pretest/posttest self-administered questionnaire. We report the short-term
      benefit of our intervention, theorize that innovative strategies targeting at
      risk older adults should be culturally sensitive and age-specifically
      appropriate, and recommend that more vigorous research methods should be
      implemented to lend credence to our findings.

PMID- 10944079
TI  - Role of a p53 polymorphism in luminal narrowing after balloon coronary
      angioplasty.

PMID- 10944080
TI  - Rapid genotype analysis of the stromelysin gene 5A/6A polymorphism.

PMID- 10944081
TI  - More on atorvastatin and fibrinogen.

PMID- 10944082
TI  - Myeloid related protein (MRP) 14 expressing monocytes infiltrate atherosclerotic
      lesions of ApoE null mice.

PMID- 10944083
TI  - Successful therapy reduces levels of vascular endothelial growth factor (VEGF) in
      patients with hypertension and patients with hypercholesterolemia.

PMID- 10944084
TI  - An evaluation of intermittent therapies used to treat onychomycosis and other
      dermatomycoses with the oral antifungal agents.

PMID- 10944085
TI  - Terbinafine, a unique oral antifungal: current perceptions.

PMID- 10944086
TI  - Degenerative collagenous plaques of the hands and acrokeratoelastoidosis:
      pathogenesis and relationship with knuckle pads.

PMID- 10944088
TI  - The molecular basis of dystrophic epidermolysis bullosa in Mexico.
AB  - BACKGROUND: Type VII collagen gene (COL7A1) mutations are the cause of dystrophic
      epidermolysis bullosa (DEB), but most mutations are specific to individual
      families, and there are limited data on the nature of COL7A1 mutations in certain
      ethnic populations. OBJECTIVE: To determine the molecular basis of DEB in
      Hispanic Mexican patients. METHODS: Patients were recruited through a newly
      established support group, Fundacion DEBRA Mexico. Molecular analysis was
      performed by polymerase chain reaction (PCR) of genomic DNA using COL7A1-specific
      primers, heteroduplex analysis, and direct nucleotide sequencing. RESULTS: Fifty
      nine of a possible 67 COL7A1 mutations (88%) were identified in 36 affected
      individuals (31 recessive, five dominant) in 21 families. Recessive mutations
      included six frameshift mutations, four silent glycine substitutions, and two
      splice-site mutations. Dominant mutations comprised a de novo glycine
      substitution and an internal deletion. Conclusions This study establishes the
      molecular basis of DEB in a group of Mexican patients. Only two of the mutations
      have been identified previously in other ethnic groups; the remainder are
      specific to this population. These new data are helpful in facilitating the
      accurate diagnosis of DEB subtype, in improving genetic counseling, and in
      providing further insight into the pathophysiology of this mechanobullous
      disease.

PMID- 10944087
TI  - Epidermolysis bullosa in Mexico.

PMID- 10944089
TI  - The relationship between Helicobacter pylori IgG antibody and autologous serum
      test in chronic urticaria.
AB  - BACKGROUND: In chronic urticaria, suspicious factors are Helicobacter pylori (HP)
      infection and autoimmunity, as well as other etiologic agents. Autologous serum
      injection is the first step to identify autoimmune urticaria. Our study was
      performed to determine the prevalence of HP infection in patients with chronic
      urticaria, and to evaluate the results of autologous serum testing in chronic
      urticaria patients who had HP antibodies. METHODS: HP immunoglobulin G (IgG)
      antibody was defined by an immunochromatographic method in 61 chronic urticaria
      patients and 15 healthy persons. Autologous serum testing was performed in 32
      chronic urticaria patients. RESULTS: HP IgG antibody was found to be positive in
      41% of chronic urticaria patients and 26% of healthy controls (chi2= 7.82, P=
      0.005). Autologous serum testing was positive in 40% of chronic urticaria
      patients who had HP IgG antibody. This ratio was 14.3% in chronic urticaria
      patients who did not have HP IgG antibody (chi2 = 9.23, P= 0.002). CONCLUSIONS:
      In this study, autologous serum testing was found to highly positive in chronic
      urticaria patients with HP IgG antibody, but the relationship between
      autoimmunity and HP infection requires further investigations.

PMID- 10944091
TI  - Eccrine poroma of the heel.

PMID- 10944090
TI  - Helicobacter pylori and idiopathic chronic urticaria.
AB  - BACKGROUND: Different studies have shown a high prevalence of Helicobacter pylori
      (HP) infection in patients with chronic urticaria (CU), and occasional remission
      of the skin lesions after eradication therapy. Recent investigations, however,
      have failed to find a significant relationship between the two conditions. We
      designed a case-control study to assess the prevalence of HP infection and the
      effect of bacterium eradication on the outcome of the skin disease in patients
      affected by CU. The literature is reviewed. METHODS: Twenty-five patients
      diagnosed with CU were included. Information about their medical history and a
      complete laboratory investigation ruled out other diseases or situations
      suspected to cause CU. Twenty-five healthy volunteers from a census-based,
      randomized sample were used as controls. HP infection was assessed by the (13)C
      urea breath test (UBT). Eradication therapy included oral amoxicillin,
      omeprazole, and clarithromycin for 1 week. RESULTS: The high prevalence of HP
      infection (68%) and mean titer of UBT (24.13) in our patients with idiopathic CU
      do not differ from the general population. Marked differences were observed in
      the mean age of the CU patients with positive UBT (45.52years) vs. those without
      HP infection (35.25 years). After eradication therapy, only one patient showed a
      complete remission of urticaria and two showed a partial remission. CONCLUSIONS:
      Our results support a lack of relationship between HP infection and the course of
      idiopathic CU.

PMID- 10944092
TI  - Chrysomyia bezziana-infested basal cell carcinoma destroying the eye.

PMID- 10944093
TI  - Cutaneous angiosarcoma afflicting the lower aspect of the left leg in an elderly
      woman.

PMID- 10944094
TI  - Vogt-Koyanagi-Harada syndrome: the useful role of punch grafting.

PMID- 10944095
TI  - Management of endemic outbreaks of scabies with allethrin, permethrin, and
      ivermectin.
AB  - BACKGROUND: At three residences for the elderly, recurrent scabies infestations
      became out of control. Due to the failure of repeated, nonsynchronized
      therapeutic efforts with conventional external anti-scabies treatments, an
      eradication program had to be developed. We describe a protocol for the
      management of outbreaks of scabies. METHODS: According to the clinical
      examination and microscopically identified mites, all individuals of the
      population (IOP: patients, staff, and family members) were divided into two
      groups: (a) healthy and infested IOP; and (b) cases with crusted scabies. The
      first group was treated simultaneously once with external scabicides (allethrin
      or permethrin). All others were hospitalized and treated either with systemic
      ivermectin or with the latter in combination with permethrin. RESULTS: In 252 IOP
      living in three residences for the elderly, clinical signs of scabies were
      reported in 91.5%, 78.5%, and 15.4% of the patients (age 55-97 years; mean, 80.5
      years), 54.1%, 32.9%, and 16.6% of staff members, and in 7%, 3%, and 0% of family
      members. The infested IOP showed crusted scabies (index cases) in 5.3%, 5.0%, and
      1.7%, common scabies in 43.1%, 36.7%, and 7.1%, and postscabiotic dermatitis in
      10.3%, 7.6%, and 3.5%. In 99.2% of the synchronously treated IOP in group (a) (n
      = 240), the conventional treatment with permethrin cream 5% or allethrin spray
      was effective. Group (b) (n=12) received ivermectin (12 mg) once (n=5) or twice
      (n= 7) after an interval of 8 days. One index case received permethrin three
      times. CONCLUSIONS: Outbreaks of scabies in populations of elderly people require
      special management for disease control. Synchronous treatment with external
      permethrin cream 5% or allethrin spray, including all IOP once, and close control
      offers a time-saving, cheap, and reliable method. Crusted scabies should be
      treated by oral administration of ivermectin once or twice after an interval of 8
      days. Additional applications of permethrin and mechanical clearing of
      hyperkeratotic subungual areas shorten the course.

PMID- 10944096
TI  - Suction blister grafting for stable vitiligo using pulsed erbium:YAG laser
      ablation for recipient site.
AB  - BACKGROUND: Suction blister grafting was performed via a modified simple
      technique using a 20-mL syringe to create the donor graft and pulsed erbium:YAG
      laser ablation of the recipient site. METHODS: Two patients with stable vitiligo
      and one with postinflammatory depigmentation were studied. RESULTS: The grafts
      took well in all three patients and pigmentation was retained at 20 weeks. No
      complications occurred. CONCLUSIONS: The erbium:YAG laser is an ideal tool for
      creating graft recipient sites, given its precision in terms of width and depth
      of ablation. A 20-mL syringe can be used to create a blister of adequate size.

PMID- 10944097
TI  - Charles Darwin consults a dermatologist.

PMID- 10944098
TI  - Endovascular treatment of an ilio-enteric fistula: a "bridge" to aortic
      homograft.

PMID- 10944099
TI  - Acute occlusion of popliteal and/or tibial arteries: the value of percutaneous
      treatment.
AB  - OBJECTIVES: to describe early and mid-term results with a percutaneous
      therapeutic protocol including thromboaspiration, thrombolysis, and correction of
      the underlying lesion by PTA. METHODS: thirty-three consecutive selected patients
      with recent (<1 month) reversible acute ischaemia associated with popliteal
      and/or tibial occlusion were studied. The primary endpoints were technical
      success (defined as residual mural thrombus less than 20% of the lumen and the
      presence of at least one tibial artery on angiogram), patient survival and limb
      salvage at 1 and 12 months. Secondary endpoints included complications, primary,
      assisted primary and secondary patency determined by duplex scan at 1, 6 and 12
      months. RESULTS: technical success was achieved in 27 patients (82%). Twenty
      patients were treated by thrombo- aspiration+/-thrombolysis only, and seven
      required additional PTA (26%). In six patients (18%), percutaneous techniques
      failed, and embolectomy was performed in two, bypass in one and major amputations
      in three (9%). For the entire series, the survival rate was 100% at 1 month and
      94% at 1 year. The limb salvage rate was 91% at 1 month and 1 year. The
      cumulative primary patency, assisted primary patency and secondary patency rates
      were 81%, 81% and 86% respectively at 1 month and 66%, 72% and 77%, respectively,
      at 12 months. Early complications occurred in 10 patients (30%): five groin
      haematomas (15%), four compartment syndromes (12%) and one haemoglobinuria (3%).
      CONCLUSION: percutaneous techniques offer excellent early and mid-term results in
      selected patients presenting with acute ischaemia with popliteal and/or tibial
      arteries occlusion.

PMID- 10944100
TI  - Risk factors for occlusion of infrainguinal bypass grafts.
AB  - OBJECTIVES: to identify risk factors for infrainguinal bypass occlusion and
      quantify the predictive value of data available before and after surgery. DESIGN:
      prospective study of 2650 patients who participated in a randomised trial of oral
      anticoagulants or aspirin after infrainguinal bypass surgery. MATERIALS AND
      METHODS: risk factors were determined by univariate Cox regression analysis, and
      entered in multivariate analyses which distinguished two models: analysis of
      factors available from history and clinical examination, completed by
      radiological and surgical data in the second model. To compare the information
      content of the two models, receiver-operator characteristic (ROC) curves were
      computed. RESULTS: in all patients female gender, critical ischaemia,
      femorocrural bypass grafting and non-venous graft material were independent risk
      factors. In patients with femoropopliteal bypasses female gender, critical
      ischaemia, poor run-off and non-venous graft material, the latter even in
      patients with supragenicular bypasses, were independent risk factors. The only
      significant risk factor in patients with femorocrural bypass grafts was use of a
      non-venous graft. The information contained in the first model was poor, whereas
      the second model had a higher predictive value. CONCLUSIONS: the major risk
      factor, even in above-knee bypasses, is non-venous graft material. The venous
      bypass graft should be offered to patients whenever possible.

PMID- 10944101
TI  - Which factors increase the risk of conversion to open surgery following
      endovascular abdominal aortic aneurysm repair? The EUROSTAR collaborators.
AB  - OBJECTIVE: to identify factors that increase the risk of conversion to open
      surgery following endovascular repair of abdominal aortic aneurysms (AAAs) and to
      assess their outcome. Design analysis of 1871 patients enrolled in the EUROSTAR
      collaborators registry. MATERIALS AND METHODS: patient characteristics, anatomic
      features of the aneurysm, type of endovascular device, institutional experience
      and the year in which the procedure was performed were related to risk of
      conversion. RESULTS: forty-nine patients (2.6%) required conversion. In 38
      patients conversion was performed during the first postoperative month (primary
      conversions) and in 11 patients during follow-up (secondary conversions). Primary
      conversion was mostly due to access problems and device migration. Secondary
      conversions were performed for rupture in six and for a persistent endoleak, with
      or without aneurysmal growth, in five patients. Patients who were converted were
      significantly older, had a lower body weight, and had a higher prevalence of
      chronic obstructive pulmonary disease. Conversion was associated with shorter,
      wider infrarenal necks and larger aneurysms. The conversion rate was lower when a
      team had performed more than 30 procedures, and in procedures performed during
      the last two years of the study period. The conversion rate was higher with EVT
      or Talent devices. Patients who required primary conversion had an 18% mortality
      rate, compared to 2.5% mortality in patients without conversion (p<0.01).
      Secondary conversion was associated with a perioperative mortality of 27%, and
      when performed for rupture 50%. CONCLUSION: both primary conversion and secondary
      conversion for rupture carry a high operative mortality. Awareness of the risk
      factors may reduce conversion rate as well as early and medium term mortality.

PMID- 10944102
TI  - Crystal structure of mammalian poly(A) polymerase in complex with an analog of
      ATP.
AB  - In eukaryotes, polyadenylation of pre-mRNA plays an essential role in the
      initiation step of protein synthesis, as well as in the export and stability of
      mRNAs. Poly(A) polymerase, the enzyme at the heart of the polyadenylation
      machinery, is a template-independent RNA polymerase which specifically
      incorporates ATP at the 3' end of mRNA. We have solved the crystal structure of
      bovine poly(A) polymerase bound to an ATP analog at 2.5 A resolution. The
      structure revealed expected and unexpected similarities to other proteins. As
      expected, the catalytic domain of poly(A) polymerase shares substantial
      structural homology with other nucleotidyl transferases such as DNA polymerase
      beta and kanamycin transferase. The C-terminal domain unexpectedly folds into a
      compact domain reminiscent of the RNA-recognition motif fold. The three invariant
      aspartates of the catalytic triad ligate two of the three active site metals. One
      of these metals also contacts the adenine ring. Furthermore, conserved,
      catalytically important residues contact the nucleotide. These contacts, taken
      together with metal coordination of the adenine base, provide a structural basis
      for ATP selection by poly(A) polymerase.

PMID- 10944103
TI  - The structure of L-amino acid oxidase reveals the substrate trajectory into an
      enantiomerically conserved active site.
AB  - The structure of L-amino acid oxidase (LAAO) from Calloselasma rhodostoma has
      been determined to 2.0 A resolution in the presence of two ligands: citrate and o
      aminobenzoate (AB). The protomer consists of three domains: an FAD-binding
      domain, a substrate-binding domain and a helical domain. The interface between
      the substrate-binding and helical domains forms a 25 A long funnel, which
      provides access to the active site. Three AB molecules are visible within the
      funnel of the LAAO-AB complex; their orientations suggest the trajectory of the
      substrate to the active site. The innermost AB molecule makes hydrogen bond
      contacts with the active site residues, Arg90 and Gly464, and the aromatic
      portion of the ligand is situated in a hydrophobic pocket. These contacts are
      proposed to mimic those of the natural substrate. Comparison of LAAO with the
      structure of mammalian D-amino acid oxidase reveals significant differences in
      their modes of substrate entry. Furthermore, a mirror-symmetrical relationship
      between the two substrate-binding sites is observed which facilitates
      enantiomeric selectivity while preserving a common arrangement of the atoms
      involved in catalysis.

PMID- 10944104
TI  - The structure and function of the beta 2-adaptin appendage domain.
AB  - The heterotetrameric AP2 adaptor (alpha, beta 2, mu 2 and sigma 2 subunits) plays
      a central role in clathrin-mediated endocytosis. We present the protein
      recruitment function and 1.7 A resolution structure of its beta 2-appendage
      domain to complement those previously determined for the mu 2 subunit and alpha
      appendage. Using structure-directed mutagenesis, we demonstrate the ability of
      the beta 2 appendage alone to bind directly to clathrin and the accessory
      proteins AP180, epsin and eps15 at the same site. Clathrin polymerization is
      promoted by binding of clathrin simultaneously to the beta 2-appendage site and
      to a second site on the adjacent beta 2 hinge. This results in the displacement
      of the other ligands from the beta 2 appendage. Thus clathrin binding to an AP2
      accessory protein complex would cause the controlled release of accessory
      proteins at sites of vesicle formation.

PMID- 10944105
TI  - Crystal structure of the matrix protein VP40 from Ebola virus.
AB  - Ebola virus maturation occurs at the plasma membrane of infected cells and
      involves the clustering of the viral matrix protein VP40 at the assembly site as
      well as its interaction with the lipid bilayer. Here we report the X-ray crystal
      structure of VP40 from Ebola virus at 2.0 A resolution. The crystal structure
      reveals that Ebola virus VP40 is topologically distinct from all other known
      viral matrix proteins, consisting of two domains with unique folds, connected by
      a flexible linker. The C-terminal domain, which is absolutely required for
      membrane binding, contains large hydrophobic patches that may be involved in the
      interaction with lipid bilayers. Likewise, a highly basic region is shared
      between the two domains. The crystal structure reveals how the molecule may be
      able to switch from a monomeric conformation to a hexameric form, as observed in
      vitro. Its implications for the assembly process are discussed.

PMID- 10944106
TI  - Redox signaling: globalization of gene expression.
AB  - Here we show that the extent of electron flow through the cbb(3) oxidase of
      Rhodobacter sphaeroides is inversely related to the expression levels of those
      photosynthesis genes that are under control of the PrrBA two-component activation
      system: the greater the electron flow, the stronger the inhibitory signal
      generated by the cbb(3) oxidase to repress photosynthesis gene expression. Using
      site-directed mutagenesis, we show that intramolecular electron transfer within
      the cbb(3) oxidase is involved in signal generation and transduction and this
      signal does not directly involve the intervention of molecular oxygen. In
      addition to the cbb(3) oxidase, the redox state of the quinone pool controls the
      transcription rate of the puc operon via the AppA-PpsR antirepressor-repressor
      system. Together, these interacting regulatory circuits are depicted in a model
      that permits us to understand the regulation by oxygen and light of
      photosynthesis gene expression in R.SPHAEROIDES:

PMID- 10944107
TI  - ACAULIS5, an Arabidopsis gene required for stem elongation, encodes a spermine
      synthase.
AB  - Polyamines have been implicated in a wide range of biological processes,
      including growth and development in bacteria and animals, but their function in
      higher plants is unclear. Here we show that the Arabidopsis: ACAULIS5 (ACL5)
      gene, whose inactivation causes a defect in the elongation of stem internodes by
      reducing cell expansion, encodes a protein that shares sequence similarity with
      the polyamine biosynthetic enzymes spermidine synthase and spermine synthase.
      Expression of the recombinant ACL5 protein in Escherichia coli showed that ACL5
      possesses spermine synthase activity. Restoration of the acl5 mutant phenotype by
      somatic reversion of a transposon-induced allele suggests a non-cell-autonomous
      function for the ACL5 gene product. We also found that expression of the ACL5
      cDNA under the control of a heat shock gene promoter in acl5 mutant plants
      restores the phenotype in a heat shock-dependent manner. The results of the
      experiments showed that polyamines play an essential role in promotion of
      internode elongation through cell expansion in Arabidopsis: We discuss the
      relationships to plant growth regulators such as auxin and gibberellins that have
      related functions.

PMID- 10944109
TI  - Dominant-negative activity of an alpha(1B)-adrenergic receptor signal
      inactivating point mutation.
AB  - alpha(1)-adrenergic receptors (alpha(1)-ARs) are members of the G-protein-coupled
      receptor (GPCR) superfamily and activate inositol phosphate (IP) turnover. We
      show that glycine and asparagine mutations of Phe303 in transmembrane segment VI
      (TMVI) of the alpha(1B)-AR, a highly conserved residue in GPCRs, although
      increasing agonist affinity, abolish agonist-activated IP signalling. Co
      expression of the Phe303 mutants also inhibited (-)epinephrine-stimulated IP
      signalling by wild-type alpha(1B)-AR and other G(q)-coupled receptors, as well as
      IP signalling mediated by AlF(4)(-) stimulation of both wild-type G(q alpha) and
      a constitutively active mutant. The inability of the Phe303 mutants to signal is
      due to induction of a receptor conformation that dissociates G-protein binding
      from activation. As a result, the Phe303 mutants sequester G(q alpha) and
      stoichiometrically inhibit Gq signalling in a dominant-negative manner. We
      further show that both the enhanced basal and agonist-stimulated IP-signalling
      activity of the constitutively active alpha(1B)-AR mutants, C128F and A293E, are
      inhibited in the double mutants, C128F/F303G and A293E/F303G. Phe303, therefore,
      appears to be critically involved in coupling TMVI alpha-helical movement, a key
      step in receptor activation, to activation of the cognate G-protein.

PMID- 10944108
TI  - Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta
      cell dysfunction.
AB  - The reverse tetracycline-dependent transactivator system was employed in
      insulinoma INS-1 cells to achieve controlled inducible expression of hepatocyte
      nuclear factor-1 alpha (HNF1 alpha)-P291fsinsC, the most common mutation
      associated with subtype 3 of maturity-onset diabetes of the young (MODY3).
      Nuclear localized HNF1 alpha-P291fsinsC protein exerts its dominant-negative
      effects by competing with endogenous HNF1 alpha for the cognate DNA-binding site.
      HNF1 alpha controls multiple genes implicated in pancreatic beta-cell function
      and notably in metabolism- secretion coupling. In addition to reduced expression
      of the genes encoding insulin, glucose transporter-2, L-pyruvate kinase, aldolase
      B and 3-hydroxy-3-methylglutaryl coenzyme A reductase, induction of HNF1 alpha
      P291fsinsC also significantly inhibits expression of mitochondrial 2-oxoglutarate
      dehydrogenase (OGDH) E1 subunit mRNA and protein. OGDH enzyme activity and
      [(14)C]pyruvate oxidation were also reduced. In contrast, the mRNA and protein
      levels of mitochondrial uncoupling protein-2 were dramatically increased by HNF1
      alpha-P291fsinsC induction. As predicted from this altered gene expression
      profile, HNF1 alpha-P291fsinsC also inhibits insulin secretory responses to
      glucose and leucine, correlated with impaired nutrient-evoked mitochondrial ATP
      production and mitochondrial membrane hyperpolarization. These unprecedented
      results suggest the molecular mechanism of HNF1 alpha-P291fsinsC causing beta
      cell dysfunction.

PMID- 10944110
TI  - Dynamin mediates caveolar sequestration of muscarinic cholinergic receptors and
      alteration in NO signaling.
AB  - In cardiac myocytes, agonist binding to muscarinic acetylcholine receptors
      (mAchRs) leads to the targeting of stimulated receptors to plasmalemmal
      microdomains termed caveolae. Here, we examined whether this translocation leads
      to mAchR internalization and alteration in downstream NO signaling. Differential
      binding of membrane-permeant and -impermeant mAchR radioligands on caveolae
      enriched membranes revealed that carbachol stimulation of cardiac myocytes
      induces sequestration of mAchRs through caveolae fission. GTP but not its non
      hydrolyzable analog GTP gamma S drove the further detachment of caveolae from
      myocyte sarcolemma. Also, incubation of extracts of carbachol-stimulated myocytes
      with recombinant GTPase dynamin induced mAchR sequestration in budded caveolae,
      while dominant-negative K44A dynamin inhibited it. These data were confirmed by
      immunofluorescence microscopy on m2 mAchR-expressing COS cells. Finally, repeated
      carbachol stimulations of mAchRs co-expressed in COS cells with endothelial
      nitric oxide synthase (eNOS) and wild-type, but not mutant, dynamin led to a
      progressive increase in mAchR sequestration and a concurrent stabilization of the
      inhibitory eNOS-caveolin complex. These findings emphasize the role of caveolae
      in mAchR trafficking and NO signaling, and suggest that caveolae fission may
      contribute to G-protein-coupled receptor desensitization.

PMID- 10944111
TI  - An intact SH3 domain is required for myosin I-induced actin polymerization.
AB  - The yeast type I myosins (MYO3 and MYO5) are involved in endocytosis and in the
      polarization of the actin cytoskeleton. The tail of these proteins contains a
      Tail Homology 2 (TH2) domain that constitutes a putative actin-binding site.
      Because of the important mechanistic implications of a second ATP-independent
      actin-binding site, we analyzed its functional relevance in vivo. Even though the
      myosin tail interacts with actin, and this interaction seems functionally
      important, deletion of a major portion of the TH2 domain did not abolish
      interaction. In contrast, we found that the SH3 domain of Myo5p significantly
      contributes to this interaction, implicating other proteins. We found that Vrp1p,
      the yeast homolog of WIP [Wiskott-Aldrich syndrome protein (WASP)-interacting
      protein], seems necessary to sustain the Myo5p tail-F-actin interaction.
      Consistent with recent results implicating the yeast type I myosins in regulating
      actin polymerization in vivo, we demonstrate that the C-terminal domain of Myo5p
      is able to induce cytosol-dependent actin polymerization in vitro, and that this
      activity requires both an intact Myo5p SH3 domain and Vrp1p.

PMID- 10944112
TI  - The protein kinase PKR is required for p38 MAPK activation and the innate immune
      response to bacterial endotoxin.
AB  - Protein kinase RNA-regulated (PKR) is an established component of innate
      antiviral immunity. Recently, PKR has been shown to be essential for signal
      transduction in other situations of cellular stress. The relationship between PKR
      and the stress-activated protein kinases (SAPKs), such as p38 mitogen-activated
      protein kinase (MAPK), is not clear. Using embryonic fibroblasts from PKR wild
      type and null mice, we established a requirement for PKR in the activation of
      SAPKs by double-stranded RNA, lipopolysaccharide (LPS) and proinflammatory
      cytokines. This does not reflect a global failure to activate SAPKs in the PKR
      null background as these kinases are activated normally by anisomycin and other
      physicochemical stress. Activation of p38 MAPK was restored in immortalized PKR
      null cells by reconstitution with human PKR. We also show that LPS induction of
      interleukin-6 and interleukin-12 mRNA is defective in PKR-null cells, and that
      production of these cytokines is impaired in PKR-null mice challenged with LPS.
      Our findings indicate, for the first time, that PKR is required for p38 MAPK
      signaling and plays a potentially important role in the innate response against
      bacterial endotoxin.

PMID- 10944113
TI  - Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel
      Lindau tumor suppressor protein.
AB  - In normoxic cells the hypoxia-inducible factor-1 alpha (HIF-1 alpha) is rapidly
      degraded by the ubiquitin-proteasome pathway, and activation of HIF-1 alpha to a
      functional form requires protein stabilization. Here we show that the product of
      the von Hippel-Lindau (VHL) tumor suppressor gene mediated ubiquitylation and
      proteasomal degradation of HIF-1 alpha under normoxic conditions via interaction
      with the core of the oxygen-dependent degradation domain of HIF-1 alpha. The
      region of VHL mediating interaction with HIF-1 alpha overlapped with a putative
      macromolecular binding site observed within the crystal structure of VHL. This
      motif of VHL also represents a mutational hotspot in tumors, and one of these
      mutations impaired interaction with HIF-1 alpha and subsequent degradation.
      Interestingly, the VHL binding site within HIF-1 alpha overlapped with one of the
      minimal transactivation domains. Protection of HIF-1 alpha against degradation by
      VHL was a multistep mechanism, including hypoxia-induced nuclear translocation of
      HIF-1 alpha and an intranuclear hypoxia-dependent signal. VHL was not released
      from HIF-1 alpha during this process. Finally, stabilization of HIF-1 alpha
      protein levels per se did not totally bypass the need of the hypoxic signal for
      generating the transactivation response.

PMID- 10944114
TI  - Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and
      activation of procaspase-9 by heat shock protein 90.
AB  - The release of cytochrome c from mitochondria results in the formation of an Apaf
      1-caspase-9 apoptosome and induces the apoptotic protease cascade by activation
      of procaspase-3. The present studies demonstrate that heat shock protein 90
      (Hsp90) forms a cytosolic complex with Apaf-1 and thereby inhibits the formation
      of the active complex. Immunodepletion of Hsp90 depletes Apaf-1 and thereby
      inhibits cytochrome c-mediated activation of caspase-9. Addition of purified Apaf
      1 to Hsp90-depleted cytosolic extracts restores cytochrome c-mediated activation
      of procaspase-9. We also show that Hsp90 inhibits cytochrome c-mediated
      oligomerization of Apaf-1 and thereby activation of procaspase-9. Furthermore,
      treatment of cells with diverse DNA-damaging agents dissociates the Hsp90-Apaf-1
      complex and relieves the inhibition of procaspase-9 activation. These findings
      provide the first evidence for a negative cytosolic regulator of cytochrome c
      dependent apoptosis and for involvement of a chaperone in the caspase cascade.

PMID- 10944115
TI  - Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell
      apoptosis.
AB  - T-cell antigen receptor (TCR)-induced thymocyte apoptosis is mediated by calcium
      dependent signal transduction pathways leading to the transcriptional activation
      of members of the Nur77 family. The major calcium- and calcineurin-responsive
      elements in the Nur77 promoter are binding sites for myocyte enhancer factor-2
      (MEF2). It has been shown that nuclear factor of activated T cells (NFAT)
      interacts with MEF2D and enhances its transcriptional activity, offering a
      plausible mechanism of activation of MEF2D by calcineurin. We report here that
      NFATp synergizes with MEF2D to recruit the coactivator p300 for the transcription
      of Nur77. Surprisingly, the enhancement of transcriptional activity of MEF2D by
      NFATp does not require its DNA-binding activity, suggesting that NFATp acts as a
      coactivator for MEF2D. Transient co-expression of p300, MEF2D, NFATp and
      constitutively active calcineurin is sufficient to recapitulate TCR signaling for
      the selective induction of the endogenous Nur77 gene. These results implicate
      NFAT as an important mediator of T-cell apoptosis and suggest that NFAT is
      capable of integrating the calcineurin signaling pathway and other pathways
      through direct protein-protein interaction with other transcription factors.

PMID- 10944116
TI  - dMi-2 and ISWI chromatin remodelling factors have distinct nucleosome binding and
      mobilization properties.
AB  - Mi-2 and ISWI, two members of the Snf2 superfamily of ATPases, reside in separate
      ATP-dependent chromatin remodelling complexes. These complexes differ in their
      biochemical properties and are believed to perform distinct functions in the
      cell. We have compared the remodelling activity of recombinant Drosophila Mi-2
      (dMi-2) with that of recombinant ISWI. Both proteins are nucleosome-stimulated
      ATPases and promote nucleosome mobilization. However, dMi-2 and ISWI differ in
      their interaction with nucleosome core particles, in their substrate requirements
      and in the direction of nucleosome mobilization. We have used antibodies to
      immobilize a complex containing dMi-2 and the dRPD3 histone deacetylase from
      Drosophila embryo extracts. This complex shares the nucleosome-stimulated ATPase
      and nucleosome mobilization properties of recombinant dMi-2, demonstrating that
      these activities are maintained in a physiological context. Its functional
      properties distinguish dMi-2 from both SWI2/SNF2 and ISWI, defining a new family
      of ATP-dependent remodelling machines.

PMID- 10944117
TI  - Both corepressor proteins SMRT and N-CoR exist in large protein complexes
      containing HDAC3.
AB  - We present evidence that both corepressors SMRT and N-CoR exist in large protein
      complexes with estimated sizes of 1.5-2 MDa in HeLa nuclear extracts. Using a
      combination of conventional and immunoaffinity chromatography, we have
      successfully isolated a SMRT complex and identified histone deacetylase 3 (HDAC3)
      and transducin (beta)-like I (TBL1), a WD-40 repeat-containing protein, as the
      subunits of the purified SMRT complex. We show that the HDAC3-containing SMRT and
      N-CoR complexes can bind to unliganded thyroid hormone receptors (TRs) in vitro.
      We demonstrate further that in Xenopus oocytes, both SMRT and N-CoR also
      associate with HDAC3 in large protein complexes and that injection of antibodies
      against HDAC3 or SMRT/N-CoR led to a partial relief of repression by unliganded
      TR/RXR. These findings thus establish both SMRT and N-CoR complexes as bona fide
      HDAC-containing complexes and shed new light on the molecular pathways by which N
      CoR and SMRT function in transcriptional repression.

PMID- 10944119
TI  - Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes.
AB  - Transport receptors of the importin beta superfamily account for many of the
      nuclear import and export events in eukaryotic cells. They mediate translocation
      through nuclear pore complexes, shuttle between nucleus and cytoplasm and co
      operate with the RanGTPase system to regulate their interactions with cargo
      molecules in a compartment-specific manner. We used affinity chromatography on
      immobilized RanGTP to isolate further candidate nuclear transport receptors and
      thereby identified exportin 4 as the most distant member of the importin beta
      family so far. Exportin 4 appears to be conserved amongst higher eukaryotes, but
      lacks obvious orthologues in yeast. It mediates nuclear export of eIF-5A
      (eukaryotic translation initiation factor 5A) and possibly that of other cargoes.
      The export signal in eIF-5A appears to be complex and to involve the hypusine
      modification that is unique to eIF-5A. We discuss possible cellular roles for
      nuclear export of eIF-5A.

PMID- 10944118
TI  - Inhibition of S-phase progression by adeno-associated virus Rep78 protein is
      mediated by hypophosphorylated pRb.
AB  - Adeno-associated virus (AAV) has an antiproliferative action on cells. We
      investigated the effect of the AAV replication proteins (Rep) on the cell
      division cycle using retroviral vectors. Rep78 and Rep68 inhibited the growth of
      primary, immortalized and transformed cells, while Rep52 and Rep40 did not. Rep68
      induced cell cycle arrest in phases G(1) and G(2), with elevated CDK inhibitor
      p21 and reduced cyclin E-, A- and B1-associated kinase activity. Rep78-expressing
      cells were also impaired in S-phase progression and accumu lated almost
      exclusively with hypophosphorylated retinoblastoma protein (pRb). The differences
      between Rep78 and Rep68 were mapped to the C-terminal zinc finger domain of
      Rep78. Rep78-induced S-phase arrest could be bypassed by adenoviral E1A or
      papillomaviral E7 proteins but not by E1A or E7 mutants unable to bind pRb. Rb(-/
      ) primary mouse embryonic fibroblasts displayed a strongly reduced S-phase arrest
      when challenged with Rep78, compared with matched Rb(+/+) controls. These results
      suggest that physiological levels of active pRb can interfere with S-phase
      progression. We propose that the AAV Rep78 protein arrests cells within S-phase
      by a novel mechanism involving the ectopic accumulation of active pRb.

PMID- 10944120
TI  - The eukaryotic mRNA decapping protein Dcp1 interacts physically and functionally
      with the eIF4F translation initiation complex.
AB  - Dcp1 plays a key role in the mRNA decay process in Saccharomyces cerevisiae,
      cleaving off the 5' cap to leave an end susceptible to exonucleolytic
      degradation. The eukaryotic initiation factor complex eIF4F, which in yeast
      contains the core components eIF4E and eIF4G, uses the cap as a binding site,
      serving as an initial point of assembly for the translation apparatus, and also
      binds the poly(A) binding protein Pab1. We show that Dcp1 binds to eIF4G and Pab1
      as free proteins, as well as to the complex eIF4E-eIF4G-Pab1. Dcp1 interacts with
      the N-terminal region of eIF4G but does not compete significantly with eIF4E or
      Pab1 for binding to eIF4G. Most importantly, eIF4G acts as a function-enhancing
      recruitment factor for Dcp1. However, eIF4E blocks this effect as a component of
      the high affinity cap-binding complex eIF4E-eIF4G. Indeed, cooperative
      enhancement of the eIF4E-cap interaction stabilizes yeast mRNAs in vivo. These
      data on interactions at the interface between translation and mRNA decay suggest
      how events at the 5' cap and 3' poly(A) tail might be coupled.

PMID- 10944121
TI  - The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization
      of the N-terminal domains.
AB  - How the ATPase activity of Heat shock protein 90 (Hsp90) is coupled to client
      protein activation remains obscure. Using truncation and missense mutants of
      Hsp90, we analysed the structural implications of its ATPase cycle. C-terminal
      truncation mutants lacking inherent dimerization displayed reduced ATPase
      activity, but dimerized in the presence of 5'-adenylamido-diphosphate (AMP-PNP),
      and AMP-PNP- promoted association of N-termini in intact Hsp90 dimers was
      demonstrated. Recruitment of p23/Sba1 to C-terminal truncation mutants also
      required AMP-PNP-dependent dimerization. The temperature- sensitive (ts) mutant
      T101I had normal ATP affinity but reduced ATPase activity and AMP-PNP-dependent N
      terminal association, whereas the ts mutant T22I displayed enhanced ATPase
      activity and AMP-PNP-dependent N-terminal dimerization, indicating a close
      correlation between these properties. The locations of these residues suggest
      that the conformation of the 'lid' segment (residues 100-121) couples ATP binding
      to N-terminal association. Consistent with this, a mutation designed to favour
      'lid' closure (A107N) substantially enhanced ATPase activity and N-terminal
      dimerization. These data show that Hsp90 has a molecular 'clamp' mechanism,
      similar to DNA gyrase and MutL, whose opening and closing by transient N-terminal
      dimerization are directly coupled to the ATPase cycle.

PMID- 10944122
TI  - Evaluating the oligomeric state of SecYEG in preprotein translocase.
AB  - SecA insertion and deinsertion through SecYEG drive preprotein translocation at
      the Escherichia coli inner membrane. We present three assessments of the theory
      that oligomers of SecYEG might form functional translocation sites. (i)
      Formaldehyde cross- linking of translocase reveals cross-links between SecY, SecE
      and SecG, but not higher order oligomers. (ii) Cross-linking of membranes
      containing unmodified SecE and hemagglutinin-tagged SecE (SecE(HA)) reveals cross
      links between SecY and SecE and between SecY and SecE(HA). However, anti-HA
      immunoprecipitates contain neither untagged SecE nor SecY cross-linked to SecE.
      (iii) Membranes containing similar amounts of SecE and SecE(HA) were saturated
      with translocation intermediate (I(29)) and detergent solubilized. Anti-HA
      immunoprecipitation of I(29) required SecYE(HA)G and SecA, yet untagged SecE was
      not present in this translocation complex. Likewise, anti-HA immunoprecipitates
      of membranes containing equal amounts of SecY and SecY(HA) were found to contain
      SecY(HA) but not SecY. Both immunoprecipitates contain more moles of I(29) than
      of the untagged subunit, again suggesting that translocation intermediates are
      not engaged with multiple copies of SecYEG. These studies suggest that the active
      form of preprotein translocase is monomeric SecYEG.

PMID- 10944123
TI  - Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and
      is regulated by DPM2.
AB  - Glycosylphosphatidylinositols (GPIs) are attached to the C-termini of many
      proteins, thereby acting as membrane anchors. Biosynthesis of GPI is initiated by
      GPI-N-acetylglucosaminyltransferase (GPI-GnT), which transfers N
      acetylglucosamine from UDP- N-acetylglucosamine to phosphatidylinositol. GPI-GnT
      is a uniquely complex glycosyltransferase, consisting of at least four proteins,
      PIG-A, PIG-H, PIG-C and GPI1. Here, we report that GPI-GnT requires another
      component, termed PIG-P, and that DPM2, which regulates dolichol-phosphate
      mannose synthase, also regulates GPI-GnT. PIG-P, a 134-amino acid protein having
      two hydrophobic domains, associates with PIG-A and GPI1. PIG-P is essential for
      GPI-GnT since a cell lacking PIG-P is GPI-anchor negative. DPM2, but not two
      other components of dolichol-phosphate-mannose synthase, associates with GPI-GnT
      through interactions with PIG-A, PIG-C and GPI1. Lec15 cell, a null mutant of
      DPM2, synthesizes early GPI intermediates, indicating that DPM2 is not essential
      for GPI-GnT; however, the enzyme activity is enhanced 3-fold in the presence of
      DPM2. These results reveal new essential and regulatory components of GPI-GnT and
      imply co-regulation of GPI-GnT and the dolichol-phosphate-mannose synthase that
      generates a mannosyl donor for GPI.

PMID- 10944124
TI  - Template definition by Tetrahymena telomerase reverse transcriptase.
AB  - The ribonucleoprotein enzyme telomerase extends chromosome ends by copying a
      specific template sequence within its integral RNA component. An active
      recombinant telomerase RNP is minimally composed of this RNA and the telomerase
      reverse transcriptase (TERT) protein, which contains sequence motifs conserved
      among viral reverse transcriptases (RTs), flanked by N- and C-terminal extensions
      specific to TERTs. We have used site-directed mutagenesis to explore the roles of
      Tetrahymena TERT in determining features of telomerase activity in general and in
      establishing the boundaries and use of an internal RNA template in specific. We
      identify a new ciliate-specific motif in the TERT N-terminus required for
      template definition. Moreover, several residues in reverse transcriptase motifs
      1, 2, A and D are critical for specific aspects of internal template use. Our
      results indicate that the unique specificity of telomerase activity is conferred
      to a reverse transcriptase active site by TERT residues both within and beyond
      the RT motif region.

PMID- 10944125
TI  - High-time chemotherapy or high time for low dose.

PMID- 10944126
TI  - Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment
      in advanced colorectal cancer.
AB  - PURPOSE: In a previous study of treatment for advanced colorectal cancer, the
      LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil
      (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment
      Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated
      the effect of combining oxaliplatin with LV5FU2, with progression-free survival
      as the primary end point. PATIENTS AND METHODS: Four hundred twenty previously
      untreated patients with measurable disease were randomized to receive a 2-hour
      infusion of LV (200 mg/m(2)/d) followed by a 5FU bolus (400 mg/m(2)/d) and 22
      hour infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone
      or together with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1. RESULTS:
      Patients allocated to oxaliplatin plus LV5FU2 had significantly longer
      progression-free survival (median, 9.0 v 6.2 months; P =.0003) and better
      response rate (50.7% v 22.3%; P =.0001) when compared with the control arm. The
      improvement in overall survival did not reach significance (median, 16.2 v 14.7
      months; P =. 12). LV5FU2 plus oxaliplatin gave higher frequencies of National
      Cancer Institute common toxicity criteria grade 3/4 neutropenia (41. 7% v 5.3% of
      patients), grade 3/4 diarrhea (11.9% v 5.3%), and grade 3 neurosensory toxicity
      (18.2% v 0%), but this did not result in impairment of quality of life (QoL).
      Survival without disease progression or deterioration in global health status was
      longer in patients allocated to oxaliplatin treatment (P =.004). CONCLUSION: The
      LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced
      colorectal cancer, demonstrating a prolonged progression-free survival with
      acceptable tolerability and maintenance of QoL.

PMID- 10944127
TI  - Oncogenes and male breast carcinoma: c-erbB-2 and p53 coexpression predicts a
      poor survival.
AB  - PURPOSE: To investigate the prognostic value of biomarkers in male breast
      carcinoma (MBC). PATIENTS AND METHODS: Fifty patients (mean age, 62.2 years) with
      invasive ductal carcinoma were retrospectively studied. All patients received
      surgery; 35 had adjuvant postoperative therapy. The median follow-up was 59
      months (range, 1 to 230 months). c-myc, c-erbB-2, p53, and bcl-2 proteins were
      immunohistochemically detected on sections from formalin-fixed, paraffin-embedded
      tissues using 9E11, CB11, DO7, and bcl-2 124 monoclonal antibodies (mAbs).
      Estrogen, progesterone, and androgen receptors were detected using specific mAbs.
      Cell proliferation was assessed by MIB-1 mAb. RESULTS: In univariate analysis, c
      myc, c-erbB-2, and p53 protein overexpression was significantly correlated with
      prognosis. The median survival was 107 months for c-myc-negative and 52 months
      for c-myc-positive patients (P =.01), 96 months for c-erbB-2-negative and 39
      months for c-erbB-2-positive patients (P =.02), and 100 months for p53-negative
      and 33 months for p53-positive patients (P =.0008). Tumor histologic grade (P
      =.01), tumor size (P =.02), patient age at diagnosis (P =.03), and MIB-1 scores
      (P =.0004) also had prognostic value. In multivariate analysis, only c-erbB-2 and
      p53 immunoreactivity retained independent prognostic significance. All nine
      patients who did not express c-erbB-2 and p53 proteins were alive after 58
      months, whereas none of the 14 patients expressing both proteins survived at 61
      months follow-up (P =.0002). CONCLUSION: Overexpression of c-myc, c-erbB-2, and
      p53 proteins may be regarded as an additional prognostic factor in MBC. The
      combination of c-erbB-2 and p53 immunoreactivity can stratify patients into
      different risk groups.

PMID- 10944128
TI  - Phase I study of paclitaxel, carboplatin, and increasing days of prolonged oral
      etoposide in ovarian, peritoneal, and tubal carcinoma: a gynecologic oncology
      group study.
AB  - PURPOSE: Given the activity of prolonged oral etoposide in platinum and
      paclitaxel-resistant ovarian carcinoma, a phase I trial was conducted that
      combined increasing days of oral etoposide therapy with paclitaxel and
      carboplatin in chemotherapy-naive patients with ovarian peritoneal and tubal
      carcinoma to establish a maximum-tolerated dose (MTD) of this combination.
      PATIENTS AND METHODS: Paclitaxel at 175 mg/m(2) given over 3 hours and
      carboplatin at an area under the curve of 5 were administered on day 1 followed
      by oral etoposide 50 mg/m(2)/d beginning on day 2. The number of days of
      etoposide therapy was escalated on the basis of toxicity. Toxicity end points
      included neutropenic sepsis, grade 4 thrombocytopenia, or grade 3 neutropenia or
      thrombocytopenia during etoposide administration. Cycles were repeated every 21
      days for a maximum of six courses. Due to hematologic toxicity, the duration of
      the paclitaxel infusion was decreased to 1 hour for a second stage of accrual.
      RESULTS: Of 52 patients studied, 29 were in the first stage of accrual. Dose
      limiting toxicity occurred with 8 days of oral etoposide, making the MTD six days
      of therapy. Twenty-three patients were entered into the second stage of accrual.
      Dose-limiting toxicity occurred at 12 days of oral etoposide, making the MTD 10
      days of therapy. Three patients developed acute myeloid leukemia 16, 27, and 35
      months after receiving a cumulative dose of 200 mg/m(2), 1,200 mg/m(2), and 2,400
      mg/m(2), respectively. CONCLUSION: One-hour paclitaxel, carboplatin, and oral
      etoposide at 50 mg/m(2)/d for 10 days is tolerable without supportive therapy.
      The leukemogenic potential is cause for concern and precludes its use in
      chemotherapy-naive ovarian carcinoma.

PMID- 10944129
TI  - Independent prognostic value of serum hepatocyte growth factor in bladder cancer.
AB  - PURPOSE: We retrospectively investigated whether the level of serum hepatocyte
      growth factor could predict the prognosis and extent of transitional-cell
      carcinoma of the urinary bladder. PATIENTS AND METHODS: Serum samples were
      collected from 113 patients with bladder cancer and from 200 healthy controls. Of
      the 113 patients, 59 had superficial bladder cancer and 54 had muscle-invasive
      cancer. Thirteen bladder cancer tissues (eight superficial and five muscle
      invasive) were also collected. The levels of hepatocyte growth factor in the
      serum and tissues of these individuals were measured by enzyme-linked
      immunoadsorbent assay using hepatocyte growth factor antibodies. RESULTS: The
      levels of hepatocyte growth factor in the serum and tissues of patients with
      muscle-invasive cancer were significantly higher than those of patients with
      superficial bladder cancer (P <.0001 and P =.0054, respectively). The degree of
      elevation above the normal level of serum hepatocyte growth factor of the former
      (61.1%) was significantly higher than that of the latter (8.4%; P <.0001). The
      elevation was highest in patients with visceral metastasis (93.3%). Among
      patients with superficial bladder cancer, the overall survival rate of those with
      low levels of serum hepatocyte growth factor was significantly greater than that
      of those with high levels (P =.005). Among patients with minimally invasive
      bladder cancer, the disease-free and overall survival rates of those with high
      levels of serum hepatocyte growth factor were significantly lower than the same
      rates of those with low levels (P <.001 and P =.0028, respectively). CONCLUSION:
      Our study suggests that the level of hepatocyte growth factor in serum could be a
      predictor of patient survival and extent of bladder cancer.

PMID- 10944130
TI  - Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for
      patients with advanced renal cell carcinoma.
AB  - PURPOSE: A randomized phase III trial was conducted to determine whether
      combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a
      (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell
      carcinoma (RCC). PATIENTS AND METHODS: Two hundred eighty-four patients were
      randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a
      alone. IFNalpha2a was given daily subcutaneously, starting at a dose of 3 million
      units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of
      3 MU), unless >/= grade 2 toxicity occurred, in which case dose escalation was
      stopped. Patients randomized to combination therapy were given oral 13-CRA 1
      mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed. RESULTS: Complete or
      partial responses were achieved by 12% of patients treated with IFNalpha2a plus
      13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of
      response (complete and partial combined) in the group treated with the
      combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to
      38 months) for the second group (P =.03). Nineteen percent of patients treated
      with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10%
      of patients treated with IFNalpha2a alone (P =.05). Median survival time for all
      patients was 15 months, with no difference in survival between the two treatment
      arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial
      recovery followed. Lower scores were associated with the combination therapy.
      CONCLUSION: Response proportion and survival did not improve significantly with
      the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13
      CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a
      sensitive tumors. Treatment, particularly the combination therapy, was associated
      with a decrease in QOL.

PMID- 10944131
TI  - Survival of patients with resected N2 non-small-cell lung cancer: evidence for a
      subclassification and implications.
AB  - PURPOSE: Patients who suffer from non-small-cell lung cancer (NSCLC) with
      ipsilateral mediastinal lymph node involvement (N2) belong to a heterogeneous
      subgroup of patients. We analyzed the prognosis of patients with resected N2
      NSCLC to propose homogeneous patient subgroups. PATIENTS AND METHODS: The present
      study comprised 702 consecutive patients from six French centers who underwent
      surgical resection of N2 NSCLC. Initially, two groups of patients were defined:
      patients with clinical N2 (cN2) and those with minimal N2 (mN2) disease were
      patients in whom N2 disease was and was not detected preoperatively at computed
      tomographic scan, respectively. RESULTS: The median duration of follow-up was 52
      months (range, 18 to 120 months). A multivariate analysis using Cox regression
      identified four negative prognostic factors, namely, cN2 status (P <. 0001),
      involvement of multiple lymph node levels (L2+; P <.0001), pT3 to T4 stage (P
      <.0001), and no preoperative chemotherapy (P <. 01). For patients treated with
      primary surgery, 5-year survival rates were as follows: mN2, one level involved
      (mN2L1, n = 244): 34%; mN2, multiple level involvement (mN2L2+, n = 78): 11%;
      cN2L1 (n = 118): 8%; and cN2L2+ (n = 122): 3%. When only patients with mN2L1
      disease were considered, the site of lymph node involvement according to the
      American Thoracic Society numbering system had no prognostic significance (P
      =.14). Preoperative chemotherapy was associated with a better prognosis for those
      with cN2 (P <.0001). Five-year survival rates were 18% and 5% for cN2 patients
      treated with and without preoperative chemotherapy, respectively. CONCLUSION:
      This study has identified homogeneous N2 NSCLC prognostic subgroups and suggests
      different therapeutic approaches according to the subgroup profile.

PMID- 10944132
TI  - Cisplatin, ifosfamide, oral etoposide, and concurrent accelerated
      hyperfractionated thoracic radiation for patients with limited small-cell lung
      carcinoma: results of radiation therapy oncology group trial 93-12.
AB  - PURPOSE: The combination of cisplatin, ifosfamide, and oral etoposide (PIEo)
      given concurrently with accelerated hyperfractionated thoracic radiation was
      studied in patients with limited small-cell lung cancer in a phase II trial to
      assess response, survival, and toxicity. PATIENTS AND METHODS: Sixty-seven
      patients were accrued between March 1994 and April 1996. Chemotherapy doses were
      cisplatin 20 mg/m(2) and ifosfamide 1,200 mg/m(2) on days 1 to 3 and etoposide 40
      mg/m(2) administered orally days 1 through 14. Radiation consisted of accelerated
      hyperfractionated thoracic radiation (AHTRT) 1.5 Gy bid x 30 fractions (total 45
      Gy) days 1 through 19, concurrent with cycle 1 of chemotherapy. Three additional
      cycles of chemotherapy were given every 4 weeks after completion of
      chemoradiation. Prophylactic cranial radiation (25 Gy in 10 fractions) was
      offered to patients for whom complete response (CR) after completion of
      chemotherapy was achieved. RESULTS: An overall objective response rate of 78% (41
      CRs [67%] and seven partial responses [11%]) was seen in 61 patients whose
      disease response could be evaluated. Median progression-free and overall survival
      estimates were 12.7 and 23.7 months, respectively. Two- and 3-year survival rates
      were estimated at 50% and 39%, respectively. Major toxic effects included grade 4
      granulocytopenia in 34 (55%), grade 4 thrombocytopenia in 16 (26%), grade 3 to 5
      fever/infection in six (10%; with one death resulting from sepsis), and grade 3/4
      esophagitis in 27 patients (43%). Other nonhematologic toxic greater than grade 2
      occurred in 11 patients (18%). CONCLUSION: Relative to conventional
      etoposide/cisplatin and concurrent AHTRT, chemoradiation with PIEo produced
      similar median and 2-year survival rates and a higher rate of acute esophageal
      toxicity. However, the locoregional control rate with a minimum follow-up of 2
      years is excellent at 80%. It is conceivable that longer follow-up will prove
      this regimen more promising. Research efforts should focus on other methods to
      improve disease control in all potential sites of recurrence.

PMID- 10944133
TI  - Phase I and pharmacologic study of docetaxel and irinotecan in advanced non-small
      cell lung cancer.
AB  - PURPOSE: We conducted a phase I trial of docetaxel, a new antimicrotubule agent,
      combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to
      determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as
      well as the dose-limiting toxicities (DLTs) of this combination in advanced non
      small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Thirty-two
      patients with stage IIIB or IV NSCLC were treated at 4-week intervals with
      docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15). The
      starting doses of docetaxel/CPT-11 were 30/40 mg/m(2), and doses were escalated
      in 10-mg/m(2) increments until the MTD was reached. RESULTS: The MTD of
      docetaxel/CPT-11 was 50/60 mg/m(2) (level 5A), or 60/50 mg/m(2) (level 5B).
      Neutropenia and diarrhea were the DLTs. CPT-11 did not affect the
      pharmacokinetics of docetaxel. There were 11 (37%) partial responses among 30
      patients. The median survival time was 48 weeks, and the 1-year survival rate was
      44.9%. CONCLUSION: The combination of docetaxel and CPT-11 seems to be active
      against NSCLC, with acceptable toxicity. The recommended dose for phase II
      studies is 50 mg/m(2) of CPT-11 (days 1, 8, and 15) and 50 mg/m(2) of docetaxel
      (day 2) administered every 28 days.

PMID- 10944134
TI  - Low-stage medulloblastoma: final analysis of trial comparing standard-dose with
      reduced-dose neuraxis irradiation.
AB  - PURPOSE: To evaluate prospectively the effects on survival, relapse-free
      survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions)
      compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in
      patients 3 to 21 years of age with low-stage medulloblastoma, minimal
      postoperative residual disease, and no evidence of neuraxis disease. PATIENTS AND
      METHODS: The Pediatric Oncology Group and Children's Cancer Group randomized 126
      patients to the study. All patients received posterior fossa irradiation to a
      total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged
      postoperatively with contrast-enhanced cranial computed tomography, myelography,
      and CSF cytology. Of the registered patients, 38 were ineligible. RESULTS: The
      planned interim analysis that resulted in closure of the protocol showed that
      patients randomized to the reduced neuraxis treatment had increased frequency of
      relapse. In the final analysis, eligible patients receiving standard-dose
      neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%),
      whereas eligible patients receiving reduced-dose neuraxis irradiation had 52%
      event-free survival at 5 years (SE = 7.7%) (P =.080). At 8 years, the respective
      EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P =.141). These
      data confirm the original one-sided conclusions but suggest that differences are
      less marked with time. CONCLUSION: Reduced-dose neuraxis irradiation (23.4 Gy) is
      associated with increased risk of early relapse, early isolated neuraxis relapse,
      and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The
      5-year EFS for patients receiving standard-dose irradiation is suboptimal, and
      improved techniques and/or therapies are needed to improve ultimate outcome.
      Chemotherapy may contribute to this improvement.

PMID- 10944135
TI  - Natural course of neuroblastoma detected by mass screening: s 5-year prospective
      study at a single institution.
AB  - PURPOSE: To describe various favorable courses of neuroblastoma (NBL) detected by
      mass screening and to present our observation program as a temporary treatment
      option, to be used until a final decision is made regarding the mass screening
      program for 6-month-old infants. PATIENTS AND METHODS: Between October 1993 and
      November 1999, 26 of 51 patients with NBL detected by mass screening were
      enrolled in our observation program. The criteria for observation included
      urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels less than
      50 microg/mg creatinine, smaller tumor size (< 5.0 cm), preoperative status, and
      granted informed consent. Patients were divided into four groups according to
      changes in urinary VMA and HVA values and tumor size. Patients who no longer
      fulfilled criteria underwent surgery. RESULTS: The observation period ranged from
      4 to 73 months. Urinary VMA and HVA levels decreased in 19 of 26 patients, often
      by age 16 months. Eighteen patients had regressing tumors, and in 10 of these
      cases, the tumor was undetectable or barely detectable by imaging techniques.
      Four patients younger than 12 months had increased tumor marker levels and tumor
      volume, histologically reflecting neuroblastic proliferation. The remaining three
      patients, all older than 18 months, had varied tumor marker levels but increased
      tumor volume, histologically reflecting an increase in Schwann cells. No
      upgrading of tumor stage or unfavorable biologic factor was noted in any patient.
      CONCLUSION: None of our patients showed evidence of transition from favorable to
      unfavorable prognosis, a finding that points to a reduction in the significance
      of screening as a public health measure. Until results of ongoing screening
      trials involving older patients have been evaluated, the observation program can
      be used as a temporary measure to avoid, with little risk, unnecessary surgical
      intervention.

PMID- 10944136
TI  - CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.
AB  - PURPOSE: To determine the frequency of CNS involvement at diagnosis of non
      Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to
      determine its prognostic significance. PATIENTS AND METHODS: We reviewed the
      records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved
      cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients;
      lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by
      serum lactate dehydrogenase (LDH) measurement and reclassification of disease
      stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of
      445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the
      CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing
      13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and
      large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis
      did not significantly impact event-free survival (P =. 095), whereas stage and
      LDH did; however, children with CNS disease at diagnosis were at 2.0 times
      greater risk of death than those without CNS disease at diagnosis. In a
      multivariate analysis, CNS disease was not significantly associated with either
      overall or event-free survival, whereas both serum LDH and stage influenced both
      overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was
      significantly associated with event-free and overall survival (univariate
      analysis); however, in multivariate analysis, only LDH had independent prognostic
      significance. Elevated serum LDH or higher modified stage were associated with a
      trend toward poorer overall survival among children with CNS disease. CONCLUSION:
      A greater tumor burden at diagnosis adversely influences the treatment outcome of
      children with NHL and CNS disease at diagnosis, suggesting a need for ongoing
      improvement in both systemic and CNS-directed therapy.

PMID- 10944137
TI  - Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's
      lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude
      des lymphomes de l'Adulte study.
AB  - PURPOSE: To present the final analysis, with a median follow-up of 8 years, of
      the LNH87-2 randomized study, which compares consolidative sequential
      chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high
      dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV
      regimen) followed by stem-cell transplantation in patients with aggressive non
      Hodgkin's lymphoma in first complete remission after induction, focusing on
      high/intermediate- and high-risk patients identified by the age-adjusted
      international prognostic index. PATIENTS AND METHODS: Among the 916 eligible
      patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After
      reaching complete remission to induction therapy, 236 of these higher risk
      patients were assessable for the consolidation phase, with 125 patients in the
      HDT arm and 111 in the sequential chemotherapy arm. RESULTS: Among these 451
      higher risk patients, 277 (61%) achieved complete remission after induction
      treatment. In the population of 236 randomized patients, HDT was superior to
      sequential chemotherapy, with 8-year disease-free survival rates of 55% (95%
      confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively
      (P =.02; relative risk, 1.56). The 8-year survival rate was significantly
      superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential
      chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk, 1.51).
      CONCLUSION: On the basis of the final analysis of this prospectively treated
      series of patients, retrospectively analyzed on the basis of the International
      Prognostic Index, we hypothesize that HDT benefits patients at higher risk who
      achieve complete remission after induction treatment.

PMID- 10944138
TI  - Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem
      cell transplantation: predictive factors for response and long-term outcome.
AB  - PURPOSE: To determine the efficacy, toxicity, and long-term outcome and
      prognostic factors of donor lymphocyte infusions (DLI) in patients with relapsed
      multiple myeloma (MM) after allogeneic stem-cell transplantation (AlloSCT).
      MATERIALS AND METHODS: Twenty-seven patients received 52 DLI courses at a median
      of 30 months after the previous AlloSCT. Reinduction therapy was administered to
      13 patients before DLI. RESULTS: Reinduction therapy was successful in eight of
      13 patients. Fourteen patients (52%) responded to DLI, including six patients
      (22%) who achieved a complete remission (CR). Five patients responded after T
      cell dose escalation in subsequent DLIs. Four patients experienced relapse or
      disease progression (three from partial response and one from CR). Five patients
      remain in remission more than 30 months after DLI. Major toxicity was acute and
      chronic graft-versus-host disease (GVHD), which was present in 55% and 26% of
      patients, respectively. Two patients died from bone marrow aplasia. Median
      overall survival of all patients was 18 months. Overall survival was 11 months
      for DLI-resistant patients and has not been reached for the responding patients.
      In two patients, sustained molecular remission was observed. The factors that
      were correlated with response to DLI were a T-cell dose of more than 1.10(8)
      cells/kg, response to reinduction therapy, and chemotherapy-sensitive disease
      before AlloSCT. CONCLUSION: These data confirm the potential and durable graft
      versus-myeloma effect of DLI in patients with relapsed MM after AlloSCT. Future
      studies should be aimed at increasing response rates, especially in patients with
      chemoresistant disease, and reducing toxicity by limiting GVHD. Adjuvant DLI
      seems an attractive and promising approach for patients who do not achieve a
      molecular remission after AlloSCT.

PMID- 10944139
TI  - The Multinational Association for Supportive Care in Cancer risk index: A
      multinational scoring system for identifying low-risk febrile neutropenic cancer
      patients.
AB  - PURPOSE: Febrile neutropenia remains a potentially life-threatening complication
      of anticancer chemotherapy, but some patients are at low risk for serious medical
      complications. The purpose of this study was to develop an internationally
      validated scoring system to identify these patients. MATERIALS AND METHODS:
      Febrile neutropenic cancer patients were observed in a prospective multinational
      study. Independent factors assessable at fever onset, predicting low risk of
      complications, on a randomly selected derivation set, were assigned integer
      weights to develop a risk-index score, which was subsequently tested on a
      validation set. RESULTS: On the derivation set (756 patients), predictive factors
      were a burden of illness indicating absence of symptoms or mild symptoms (weight,
      5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or
      moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of
      hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic
      obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46);
      presence of solid tumor or absence of previous fungal infection in patients with
      hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient
      status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration
      (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight,
      2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational
      Association for Supportive Care in Cancer risk-index score >/= 21 identified low
      risk patients with a positive predictive value of 91%, specificity of 68%, and
      sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at
      low risk for complications and may be used to select patients for testing
      therapeutic strategies that may be more convenient or cost-effective.

PMID- 10944140
TI  - Effect of providing cancer patients with the audiotaped initial consultation on
      satisfaction, recall, and quality of life: a randomized, double-blind study.
AB  - PURPOSE: By means of a randomized double-blind study, the effect of providing
      taped initial consultations on cancer patients' satisfaction, recall, and quality
      of life was investigated. PATIENTS AND METHODS: Consecutive cancer patients
      referred to either the gynecology or medical oncology outpatient clinic were
      eligible. Initial consultations were audiotaped. Patients were either provided
      with the tape (experimental group) or not (control group). Baseline variables
      included sociodemographics, preferences for information, coping styles, and
      clinical characteristics. Follow-up (after 1 week and 3 months) variables
      included attitudes toward the intervention, satisfaction, recall, and quality of
      life. Assessments took place through mailed questionnaires and telephone
      interviews. RESULTS: Two hundred one patients were included (response, 71%), 105
      in the experimental group and 96 in the control group. Most patients (75%)
      listened to the tape, the majority of which (73%) listened with others. Almost
      all patients, both in the experimental group (96%) and control group (98%) were
      positive about the intervention. Expectations were confirmed; patients provided
      with the tape were more satisfied (P <.05) and recalled more information (P <.01)
      than patients without the tape. The intervention did not have an effect on
      quality of life. An interaction effect was found between the intervention and
      patients' age on satisfaction with the taped consultation (P <.01) and recall of
      diagnostic information (P <.01); access to tapes seems more helpful in enhancing
      satisfaction in younger patients and recall of diagnostic information in older
      patients. CONCLUSION: Cancer patients and their families value the taped initial
      consultation. This intervention enhances their satisfaction and improves their
      recall of information. Tapes seem more helpful in enhancing satisfaction in
      younger patients and recall of diagnostic information in older patients.

PMID- 10944141
TI  - Adjuvant chemotherapy in gastric cancer.

PMID- 10944142
TI  - Does total-body irradiation technique influence veno-occlusive disease incidence?

PMID- 10944143
TI  - Optimum methods to mobilize stem cells.

PMID- 10944144
TI  - Dexrazoxane in anthracycline extravasation.

PMID- 10944145
TI  - The use of mutants to probe models of gravitropism.
AB  - It has been widely believed for more than 70 years that auxin plays a central
      role in the induction of differential growth which causes gravitropic curvature.
      However, this long-standing consensus about a role for auxin in gravitropism has
      only been achieved by allowing several mutually exclusive models to coexist.
      Furthermore, because there is no detailed model which is unchallenged by
      evidence, consensus is now centred on ill-defined models which have a low
      predictive value, hence are harder to challenge experimentally. An increasing
      number of mutants with abnormal gravitropic behaviour are becoming available.
      Such mutants should be very helpful in challenging existing models of
      gravitropism and in providing new evidence on which to build improved, more
      precise models. However, to date, most studies of mutants with abnormal
      gravitropism have been guided, experimentally and conceptually, by the old
      inadequate and vague models. Consequently, the full potential of modern molecular
      analysis in aiding our understanding of gravitropism has yet to be realized.

PMID- 10944146
TI  - Active transport of CO(2) and bicarbonate is induced in response to external
      CO(2) concentration in the green alga Chlorella kessleri.
AB  - The time-course of induction of CO(2) and HCO(3)- transport has been investigated
      during the acclimation of high CO(2)-grown Chlorella kessleri cells to dissolved
      inorganic carbon (DIC)-limited conditions. The rate of photosynthesis of the
      cells in excess of the uncatalysed supply rate of CO(2) from HCO(3)- was taken as
      an indicator of HCO(3)- transport, while a stimulation of photosynthesis on the
      addition of bovine carbonic anhydrase was used as an indicator of CO(2)
      transport. The maximum rate of photosynthesis (Pmax) was similar for high CO(2)
      grown and low CO(2)-grown cells, but the apparent whole cell affinity for DIC and
      CO(2) of high CO(2)-grown cells was found to be about 30-fold greater than in air
      grown cells, which indicates a lower affinity for DIC and CO(2). It was found
      that HCO(3)- and CO(2) transport were induced in 5.5 h in cells acclimating to
      air in the light and in the presence and absence of 21% O(2), which indicates
      that a change in the CO(2)/O(2) ratio in the acclimating medium does not trigger
      induction of DIC transport. No active DIC transport was detected in high CO(2)
      grown cells maintained on high CO(2) for 5.5 h in the presence of 5 mM
      aminooxyacetate, an aminotransferase inhibitor. These results indicate no
      involvement of photorespiration in triggering induction. Active DIC transport
      induction was inhibited in cells treated with 5 microgram ml(-1) cycloheximide,
      but was unaffected by chloramphenicol treatment, indicating that the induction
      process requires de novo cytoplasmic protein synthesis. The total DIC
      concentration eliciting the induction and repression of CO(2) and HCO(3)-
      transport was higher at pH 7.5 than at pH 6.6. The concentrations of external
      CO(2) required for the induction and repression of DIC transport were 0 and 120
      microM, respectively, and was independent of the pH of the acclimation medium.
      Prolonged exposure to a critical external CO(2) concentration elicits the
      induction of DIC transport in C. kessleri.

PMID- 10944147
TI  - Short-term nitrogen-induced modulation of phosphoenolpyruvate carboxylase in
      tobacco and maize leaves.
AB  - Untransformed maize and tobacco plants and tobacco plants constitutively
      expressing nitrate reductase were grown with sufficient NO(3)- to support maximal
      growth. Four days prior to treatment the tobacco plants were deprived of
      nitrogen. Excised maize leaves and tobacco leaf discs were fed with either 40 mM
      KNO(3) or 40 mM KCl (control) in the light. Phosphoenolpyruvate (PEP) carboxylase
      (Case) activity was measured at 0.3 mM and 3 mM PEP. The light- induced increase
      in PEPCase V(max) was greater in maize than tobacco. Furthermore light decreased
      malate sensitivity in maize (which was N-replete) but not in N-deficient tobacco.
      NO(3)- treatment increased PEPCase V:(max) values in both species and decreased
      the sensitivity to inhibition by malate, but effects of NO(3)- were much more
      pronounced in tobacco than maize. PEPCase kinase activity was, however, greater
      in maize leaves NO(3)- than in the Cl(-)-treated controls, suggesting that it is
      responsive to leaf nitrogen supply. A correlation between foliar glutamine
      content and PEPCase activity was observed. It is concluded that PEPCase is
      sensitive to N metabolites which favour increased flow through the anapleurotic
      pathway in both C(3) and C(4) plants.

PMID- 10944148
TI  - B-type granule containing protrusions and interconnections between amyloplasts in
      developing wheat endosperm revealed by transmission electron microscopy and GFP
      expression.
AB  - Starch granules in mature wheat endosperm show a bimodal size distribution. The
      formation of small starch granules in wheat endosperm cells was studied by
      transmission electron microscopy (TEM) and confocal laser scanning microscopy
      (CLSM) after expression and targeting of fluorescent protein into amyloplasts.
      Both techniques demonstrated the presence of protrusions emanating from A-type
      granules-containing amyloplasts and the presence of B-type starch granules in
      these evaginations. Moreover, CLSM recordings demonstrated the interconnection of
      the amyloplasts by these protrusions, suggesting a possible role of these
      protrusions in interplastid communication.

PMID- 10944149
TI  - Lipid hydroperoxide levels in plant tissues.
AB  - Hydroperoxides are the primary oxygenated products of polyunsaturated fatty acids
      and are key intermediates in the octadecanoid signalling pathway in plants. Lipid
      hydroperoxides (LHPO) were determined spectrophotometrically based on their
      reaction with an excess of Fe(2+)at low pH in the presence of the dye xylenol
      orange. Triphenylphosphine-mediated hydroxide formation was used to authenticate
      the signal generated by the hydroperoxides. The method readily detected lipid
      peroxidation in Phaseolus: microsomes, senescing potato leaves and in a range of
      other plant tissues including Phaseolus hypocotyls (26+/-5 nmol g(-1) FW),
      Alstroemeria floral tissues (sepals 66+/-13 nmol g(-1) FW petals 49+/-6 nmol g(
      1) FW), potato leaves (334+/-75 nmol g(-1) FW), broccoli florets (568+/-68 nmol
      g(-1) FW) and Chlamydomonas cells (602+/-40 nmol g(-1) FW). Relative to the total
      fatty acid content of the tissues, the % LHPO was within the range of 0.6-1.7%
      for all tissue types (photosynthetic and non-photosynthetic) and represents the
      basal oxidation level of membrane fatty acids in plant cells. In order to relate
      the levels of LHPO to specific signalling pathways, transgenic potato plant lines
      were used in which lipoxygenase (LOX) (responsible for hydroperoxide
      biosynthesis) and hydroperoxide lyase (a route of hydroperoxide degradation)
      activities were largely reduced by an antisense-mediated approach. While the LHPO
      levels were similar to wild type in the individual LOX antisensed plants, basal
      LHPO levels, by contrast, were elevated by 38% in transgenic potato leaves
      antisensed in hydroperoxide lyase, indicating a role for this enzyme in the
      maintenance of cellular levels of LHPOs.

PMID- 10944150
TI  - The second step of the biphasic endosperm cap weakening that mediates tomato
      (Lycopersicon esculentum) seed germination is under control of ABA.
AB  - The role of abscisic acid (ABA) in the weakening of the endosperm cap prior to
      radicle protrusion in tomato (Lycopersicon esculentum Mill. cv. Moneymaker) seeds
      was studied. The endosperm cap weakened substantially in both water and ABA
      during the first 38 h of imbibition. After 38 h the force required for endosperm
      cap puncturing was arrested at 0.35 N in ABA, whereas in water a further decrease
      occurred until the radicle protruded. During the first 2 d of imbibition endo
      beta-mannanase activity was correlated with the decrease in required puncture
      force and with the appearance of ice-crystal-induced porosity in the cell walls
      as observed by scanning electron microscopy. Prolonged incubation in ABA resulted
      in the loss of endo-beta-mannanase activity and the loss of ice-crystal-induced
      porosity, but not in a reversion of the required puncture force. ABA also had a
      distinct but minor effect on the growth potential of the embryo. However,
      endosperm cap resistance played the limiting role in the completion of
      germination. It was concluded that (a) endosperm cap weakening is a biphasic
      process and (b) inhibition of germination by ABA is through the second step in
      the endosperm cap weakening process.

PMID- 10944151
TI  - Development of beta-1,3-glucanase activity in germinated tomato seeds.
AB  - Laminarin-hydrolysing activity developed in the endosperm of tomato (Lycopersicon
      esculentum) seeds following germination. The enzyme was basic (pI>10) and the
      apparent molecular mass was estimated to be 35 kDa by SDS-PAGE. It was specific
      for linear beta-1,3-glucan substrates. Laminarin was hydrolysed by the enzyme to
      yield a mixture of oligoglucosides, indicating that the enzyme had an endo-action
      pattern. Thus, the enzyme was identified as beta-1,3- endoglucanase (EC
      3.2.1.39). The activity of the enzyme developed in the endosperm after radicle
      protrusion (germination) had occurred and the enzyme activity was localized
      exclusively in the micropylar region of the endosperm where the radicle had
      penetrated. When the lateral endosperm region, where no induction of the enzyme
      occurred, was wounded (cut or punctured), there was a marked enhancement of beta
      1,3-glucanase activity. Thus the post-germinative beta-1, 3-glucanase activity in
      the micropylar endosperm portion might be brought about by wounding resulting
      from endosperm rupture by radicle penetration.

PMID- 10944152
TI  - Evidence of active NADP(+) phosphatase in dormant seeds of Avena sativa L.
AB  - Freshly-harvested seeds of Avena sativa L. do not germinate when imbibed at
      temperatures higher than 25 degrees C. This high temperature dormancy is due to
      the seed coats, and to the low activities of glycolysis and the oxidative pentose
      phosphate pathway (OPP) in the embryo. The analysis by exclusion chromatography
      of soluble NADP(+) phosphatase activities of embryos revealed two isoforms: a 37
      kDa isoform present in both dormant and after-ripened caryopses, and a second
      isoform, with an apparent molecular weight of 160 kDa, five times more active in
      embryos of dormant seeds than in the after-ripened ones, after 6 h of imbibition
      at 30 degrees C. Moreover, the activity of this 160 kDa isoform was three times
      less in embryos from dormant caryopses when they were grown at 10 degrees C, a
      permissive temperature for radicle protrusion. These results suggest a
      correlation between the activity of the 160 kDa NADP(+) phosphatase and the
      dormancy state of the caryopsis. The two isoforms differed in the pH required for
      optimal activity: pH 5.7 and 6.5 for the 37 kDa and the 160 kDa phosphatases,
      respectively. Furthermore, the 160 kDa NADP(+) phosphatase displayed a strong
      specificity for NADP(+), whereas the 37 kDa isoform was able to hydrolyse
      numerous other phosphorylated compounds.

PMID- 10944153
TI  - A comparison of proteins from the developing xylem of compression and non
      compression wood of branches of sitka spruce (Picea sitchensis) reveals a
      differentially expressed laccase.
AB  - Soluble and cell wall-associated proteins were extracted from the developing
      xylem of the compression and non-compression sides of branches of Sitka spruce
      (Picea sitchensis (Bong) Carr.) by an identical procedure. Equal amounts of
      proteins were separated by SDS-PAGE, and polypeptides were identified that were
      more abundant in soluble and cell wall-associated extracts from the developing
      xylem of either compression or non-compression wood. Two polypeptides (at
      apparent M(r)s of 48 kDa and 120 kDa) that were more abundant in cell wall
      associated extracts of the developing xylem of the compression tissues were
      selected for amino-terminal protein sequencing. The 48 kDa polypeptide yielded an
      amino-terminal sequence that had no homology with known protein, gene or EST
      database sequences. The amino-terminal sequence of the 120 kDa polypeptide was
      homologous to a number of laccase-type polyphenol oxidases (EC 1.10.3.2) thought
      to be involved in lignin biosynthesis in trees. Using non-denaturing SDS-PAGE,
      the 120 kDa laccase was confirmed as a major oxidase activity in extracts of
      lignifying compression xylem but it was barely detectable in the non-compression
      extracts where an 85 kDa oxidase was the predominant activity. The differential
      expression of oxidases in compression and non-compression xylem is discussed.

PMID- 10944154
TI  - Hormonal influence on photocontrol of the protandry in the genus Helianthus.
AB  - Under natural photoperiodic conditions protandry in hermaphrodite disc flowers of
      sunflower (Helianthus annuus L.) is determined by the different elongation rates
      of the style and filaments. The elongation of the filament and style starts
      simultaneously after the daily dark period, but the style growth rate is slower.
      When plants close to anthesis are exposed to continuous white light (WL) a loss
      of protandry occurs: the filaments do not grow far enough to extrude the anthers
      from the corolla. The histological analyses show that the number of filament
      epidermal cells remains unaltered after organ elongation and that cells respond
      to photoperiod only by cell expansion. Emasculation does not substantially
      inhibit filament cell expansion, whereas isolation of the filament or stamen from
      the corolla suggests that this organ could be the perception site of the filament
      growth stimulus. In vitro treatments with auxin (indole-3-acetic acid, IAA or
      alpha-naphthaleneacetic acid, NAA) reverses the inhibition of cell expansion
      caused by continuous WL, whereas gibberellic acid (GA(3)) at high concentrations
      reproduces the effect of continuous WL. Experiments carried out on various
      Helianthus spp. show that all these plants have evolved the same photo- and
      hormonal-control of the protandry. In experiments in which the light treatments
      were continued for 24 h, the auxins drastically reduced the inhibiting effect of
      red light (R) and dichromatic treatments FR (far red)+R, whereas GA(3) repressed
      filament extension regardless of light quality. As far as auxins are concerned,
      the response of sunflower filaments does not appear to be connected with the
      polar transport of the hormone. Moreover, the promoting effect of darkness is not
      mediated by an increase of endogenous free IAA in disc flowers. However,
      sunflower filaments manifested a similar temporal pattern of response to the
      light/dark cycle and to auxin.

PMID- 10944155
TI  - Anoxia tolerance in the aquatic monocot Potamogeton pectinatus absence of oxygen
      stimulates elongation in association with an unusually large pasteur effect.
AB  - Elongation by stems of overwintered tubers of Potamogeton pectinatus (L.) is
      strongly promoted over several days by oxygen-free conditions. Characteristics of
      the respiration underpinning this unusual response were examined. Anaerobic
      plants produced ethanol and CO(2) in approximately equimolar amounts, indicating
      that glycolysis coupled to alcoholic fermentation was the principal CO(2)
      producing respiratory pathway. Rates of CO(2) evolution by aerobic and anaerobic
      whole plants (shoot and tuber) were similar, suggesting a rate of glycolysis
      three times that of aerobic plants, i.e. a strong Pasteur effect. In the shoot
      alone, anaerobic CO(2) production was twice the aerobic rate indicating a 6-fold
      increase in the rate of glycolysis in this tissue. Anoxic stems contained more
      sucrose at a stronger concentration than slower-growing aerobic stems or
      anaerobic leaves, demonstrating that sugar supply to the site of most rapid
      growth exceeded demand in the absence of oxygen. Concentrations of potentially
      toxic acetaldehyde in the external medium were small (approximately 0.2 mol m(
      3)) during anoxia and on return to aerated conditions. Lactic acid was
      undetectable under anaerobic conditions and in vivo (31)P-NMR analysis of shoots
      revealed a cytoplasmic acidification of only </=0.2 pH units. In contrast, shoots
      of Pisum sativum, an anoxia-intolerant species, showed much stronger cytoplasmic
      acidification when transferred to oxygen-free conditions.

PMID- 10944157
TI  - Light-induced stomatal movement of selected Arabidopsis thaliana mutants.
AB  - Various Arabidopsis thaliana mutants with defects in phytohormone signal
      transduction or the reception of light were analysed with regard to their
      stomatal response in a red, red/blue light irradiation programme. Stomatal
      response to light was detected with a customized gas exchange measurement device,
      optimized for the small model plant. Small transpiration-kinetic variations of
      the two wild-type lines Columbia (Col) and Landsberg erecta (Ler) were observed.
      A comparison of the mutant lines to the respective wild type revealed significant
      differences for the phytochrome A (phyA-103), the abscisic acid insensitive (aba3
      2) and the auxin resistant (axr1-3) mutant. Furthermore, the zeaxanthin-less
      mutant line npq1-2 showed no alterations in stomatal response to light.

PMID- 10944156
TI  - Comparison of globulin mobilization and cysteine proteinases in embryonic axes
      and cotyledons during germination and seedling growth of vetch (Vicia sativa L.).
AB  - Vicilin and legumin, the storage globulins of mature dry vetch (Vicia sativa L.)
      seeds, are found in protein bodies which are present not only in the cotyledons,
      but also in the radicle, axis and shoot (together, for reasons of simplicity,
      here called axis). When at 24 h after the start of imbibition (hai) the radicle
      breaks through the seed coat a major part of the globulins in the axis has
      already been degraded, whereas in the cotyledons globulin breakdown cannot yet be
      detected. Globulin mobilization starts with the degradation of vicilin. At 48 hai
      when globulin mobilization in the cotyledons just begins, the axis is already
      nearly depleted of globulins. Mobilization of storage globulin is probably
      brought about by a complex of different cysteine proteinases (CPRs). The papain
      like CPR2 and CPR4, and the legumain-like VsPB2, together with their mRNAs, are
      already present in axes and cotyledons of dry seeds. This means that they must
      have been formed during seed maturation. Additional papain-like CPRs are formed
      later during germination and seedling growth. CPR4 and VsPB2 together with their
      corresponding mRNAs become undetectable as germination and seedling growth
      proceed. VsPB2 and VsPB2-mRNA are substituted by the homologous legumain-like
      proteinase B and its mRNA. The composition of stored and newly formed CPRs
      undergoes developmental changes which differ between axes and cotyledons. It is
      concluded that storage globulin mobilization in germinating vetch seeds is
      started by stored CPRs, whereas the mobilization of the bulk of globulin is
      predominantly mediated by CPRs which are formed de novo.

PMID- 10944158
TI  - Hydrolytic enzymes and ability of arbuscular mycorrhizal fungi to colonize roots.
AB  - The production of hydrolytic enzymes from external mycelia associated with roots
      and colonized soybean roots (Glycine max L.) inoculated with different arbuscular
      mycorrhizal (AM) fungi of the genus GLOMUS:, and the possible relationship
      between these activities and the capacity of the AM fungi to colonize plant roots
      was studied. There were differences in root colonization and plant growth between
      the GLOMUS: strains, and also between two isolates of G. mosseae. Hydrolytic
      activities in the root and external mycelia associated with roots differed in the
      AM fungi tested. Correlations were only found between the endoxyloglucanase
      activity of the external mycelia associated with roots of the AM fungi tested and
      the percentage root colonization or plant growth. However, hydrolytic activities
      of roots colonized by the different endophytes correlated with those of external
      mycelia. The hydrolytic activities were not qualitatively different because the
      endoxyloglucanase from AM colonized roots and the external mycelia did not show a
      high degree of polymorphism in the different species of fungus tested. The
      possible role of the hydrolytic activity of external hyphae of AM fungi was
      discussed as a factor affecting fungal ability to colonize the root and influence
      plant growth.

PMID- 10944159
TI  - Effect of nitrogen supply and defoliation on loss of organic compounds from roots
      of Festuca rubra.
AB  - The aim of this study was to determine the effects of N-supply and defoliation on
      rhizodeposition from Festuca rubra, in the context of whole-plant C- partitioning
      and root morphology. Plants were grown for 36 d in axenic sand microcosms
      continuously percolated with nutrient solutions of either high or low N
      concentration (2 mM or 0.01 mM NH(4)NO(3), respectively). The effects of partial
      defoliation at weekly intervals were determined at high and low N. At low N, dry
      matter accumulation in roots and shoots was reduced significantly (P<0.001), with
      proportionately increased partitioning to roots, in comparison with the high N
      treatment. Root morphology was also affected by N-treatment; at low N, lower
      biomass production was offset by increased specific root length (P<0.001),
      reducing the magnitude of the significant (P=0.002) increase in total root length
      at high N. Cumulative release of organic C from roots of F: rubra over the
      experimental period was not altered significantly by N-treatment. However, as a
      proportion of net C-assimilation, rhizodeposition was significantly (P<0.001)
      greater at low N than at high N. Defoliation transiently (3-5 d) increased the
      release of soluble organic compounds from roots at each N-supply rate, and
      increased significantly (P<0.001) cumulative rhizodeposition over the
      experimental period. These effects of N-supply and defoliation on rhizodeposition
      are of importance in understanding interactions between plant and microbial
      productivity in grazed grasslands, and in interpretation of concurrent effects on
      microbially driven nutrient cycling processes in these systems.

PMID- 10944160
TI  - Ureide degradation pathways in intact soybean leaves.
AB  - Ureides dramatically accumulate in shoots of N(2)-fixing soybean (Glycine max L.
      Merr.) under water deficit and this accumulation is higher in cultivars that have
      N(2) fixation that is sensitive to water deficit. One possible explanation is
      that ureide accumulation is associated with a feedback inhibition of nitrogenase
      activity. A critical factor involved in ureide accumulation is likely to be the
      rate of ureide degradation in the leaves. There exists, however, a controversy
      concerning the pathway of allantoic acid degradation in soybean. Allantoate
      amidinohydrolase was reported to be the pathway of degradation in studies using
      the cultivar Maple Arrow and allantoate amidohydrolase was the pathway that
      existed in the cultivar Williams. This investigation was undertaken to resolve
      the existence of these two pathways. An in situ technique was developed to
      examine the response of ureide degradation in leaf tissue to various treatments.
      In addition, the response of ureide accumulation and N(2) fixation activity was
      measured for intact plants in response to treatments that differentially
      influenced the two degradation pathways. The results from these studies confirmed
      that Maple Arrow and Williams degraded allantoic acid by different pathways as
      originally reported. The existence of two degradation pathways within the soybean
      germplasm opens the possibility of modifying ureide degradation to minimize the
      influence of soil water deficits on N(2) fixation activity.

PMID- 10944161
TI  - A simple method to determine leaf angles of grass species.
AB  - There are several very accurate methods to determine leaf angles in closed
      canopies. However, these are generally very time-consuming or require special
      equipment. Average canopy leaf angles were derived from simple height and blade
      length measurements. An exponential relationship between the height/length ratio
      and the average blade leaf angle was used. The method was tested for two grass
      species, Dactylis glomerata and Festuca arundinacea, grown under different UV-B
      levels. The results clearly show that the method is reasonably accurate and able
      to identify UV-B induced changes in leaf angle. To get these results only 50
      measurements of leaf blade height and length were necessary to calculate the
      allometric relationship, after which 10 length and height measurements from a
      canopy were used to calculate the average canopy leaf angle.

PMID- 10944162
TI  - Non-invasive photoacoustic spectroscopic determination of relative endogenous
      nitric oxide and ethylene content stoichiometry during the ripening of
      strawberries Fragaria anannasa (Duch.) and avocados Persea americana (Mill.).
AB  - Employing non-invasive photoacoustic spectrometry, emissions of nitric oxide (NO)
      and ethylene in post-harvest strawberries and avocados were monitored. A clear
      cut stoichiometric relationship was found between the two gases: unripe fruit
      manifesting high NO and low ethylene levels-the converse in ripe fruit. Findings
      are discussed in the light of putative control of ethylene-promoted fruit
      senescence by endogenous NO.

PMID- 10944163
TI  - The significance of alpha-amylase under anoxia stress in tolerant rhizomes
      (Acorus calamus L.) and non-tolerant tubers (Solanum tuberosum l., var. Desiree).
AB  - Rhizomes of Acorus calamus L. were able to maintain a functional alpha-amylase
      under anoxia, whereas a steep decrease in the enzyme protein content and activity
      took place in potato tubers. The stress-induced control in tubers occurred on the
      translational level. It is suggested that this decrease is one of the key factors
      with regard to anoxia intolerance.

PMID- 10944164
TI  - Abg1: a novel gene up-regulated by abscisic acid in guard cells of Vicia faba L.
AB  - A novel gene (abg1) was isolated by differential display RT-PCR from guard cells
      of Vicia faba L. Abg1 transcript accumulated in guard cells that were incubated
      with 5 microM S(+)-ABA for 1 h. The full-length abg1 cDNA was 753 bp, which
      included a 513 bp coding region. The deduced 17.8 kDa protein shared sequence
      similarity with several desiccation-related proteins reported in plants.

PMID- 10944165
TI  - Chronicle of skinned muscle fibres.

PMID- 10944166
TI  - Laminin binding to beta1-integrins selectively alters beta1- and beta2
      adrenoceptor signalling in cat atrial myocytes.
AB  - 1. Perforated patch recordings were used to determine how plating atrial cells on
      laminin alters beta-adrenergic receptor (beta-AR) regulation of L-type Ca2+
      current (ICa,L). 2. Isoproterenol (isoprenaline; ISO; 0.01 microM), a non
      selective beta-AR agonist, elicited a greater stimulation of ICa,L in cells
      plated on laminin (+79 +/- 16 %; n = 17) than on glass (+33 +/- 5 %; n = 23).
      Also, desensitization to ISO was greater in cells on laminin (-16 +/- 2 %) than
      on glass (-3 +/- 1 %). Atenolol (0.1 microM), a selective beta1-AR antagonist,
      inhibited the effects of ISO in cells on glass but not laminin. Conversely, 0.1
      microM ICI 118,551, a selective beta2-AR antagonist, inhibited the effects of ISO
      in cells on laminin but not glass. With beta2-ARs blocked, ISO-induced
      stimulation of ICa,L was greater in cells on glass than laminin. 3. Zinterol
      (0.01-0.1 microM), a selective beta2-AR agonist, elicited a greater stimulation
      of ICa,L in cells on laminin than on glass. The effects of zinterol were blocked
      by ICI 118,551. 4. ISO-induced stimulation of ICa,L was greater in cells plated
      on an alphabeta1-integrin antibody than on glass. Also, addition of 20 microM
      cytochalasin D to cells on laminin prevented the enhanced effects of ISO
      typically elicited in cells on laminin alone. 5. We conclude that laminin binding
      to alphabeta1-integrins, in conjunction with the actin cytoskeleton, reduces
      beta1-AR and enhances beta2-AR signalling which regulates ICa,L. This novel
      mechanism may contribute to remodelling of beta-AR signalling in the failing
      heart.

PMID- 10944167
TI  - Single-channel properties of neuronal GABAA receptors from mice lacking the 2
      subunit.
AB  - 1. The aim of this study was to define the biophysical properties contributed by
      the gamma2 subunit to native single GABAA receptors. 2. Single-channel activity
      was recorded from neurones of wild-type (gamma2+/+) mice and compared with that
      from mice which were heterozygous (gamma2+/-) or homozygous (gamma2-/-) for a
      targeted disruption in the gamma2 subunit gene of the GABAA receptor. Unitary
      currents were evoked by low concentrations of GABA (0.5-5 microM) in membrane
      patches from acutely isolated dorsal root ganglion (DRG) neurones (postnatal day
      0) and by 1 microM GABA in patches from embryonic hippocampal neurones which were
      cultured for up to 3 weeks. 3. GABAA receptors from DRG and hippocampal neurones
      of gamma2+/+ and gamma2+/- mice displayed predominantly a conductance state of 28
      pS and less frequently 18 and 12 pS states. In gamma2-/- mice, conductance states
      mainly of 12 pS and less frequently of 24 pS were found. 4. The mean open
      duration of the 28 pS state in gamma2+/+ GABAA receptors (1.5-2.6 ms) was
      substantially longer than for the 12 pS state of gamma2-/- GABAA receptors (0.9
      1.2 ms) at all GABA concentrations. For gamma2+/+ and gamma2-/- channels, the
      mean open duration was increased at higher GABA concentrations. 5. Open duration
      frequency distributions of 28 and 12 pS receptors revealed the existence of at
      least three exponential components. Components with short mean durations declined
      and components with long mean durations increased in relative frequency at higher
      GABA concentration indicating at least two binding sites of GABA per 28 and 12 pS
      receptor. 6. Shut time frequency distributions revealed at least four exponential
      components of which two were identified as intraburst components in 28 pS and one
      in 12 pS GABAA receptors. 7. The mean burst duration and the mean number of
      openings per burst increased in 28 and 12 pS GABAA receptors with increasing GABA
      concentration. At least two burst types were identified: simple bursts consisting
      of single openings and complex bursts of five to six openings in 28 pS but only
      two to three openings in 12 pS GABAA receptors. 8. We conclude that the gamma2
      subunit enhances the efficacy of GABA by determining open conformations of high
      conductance and long lifetime, and by prolonging the time receptors remain in the
      activated bursting state.

PMID- 10944168
TI  - Action potential-evoked Ca2+ signals and calcium channels in axons of developing
      rat cerebellar interneurones.
AB  - Axonal [Ca2+] transients evoked by action potential (AP) propagation were studied
      by monitoring the fluorescence of the high-affinity calcium-sensitive dye Oregon
      Green 488 BAPTA-1, introduced through whole-cell recording pipettes in the
      molecular layer of interneurones from cerebellar slices of young rats. The
      spatiotemporal profile of Ca2+-dependent fluorescence changes was analysed in
      well-focused axonal stretches a few tens of micrometres long. AP-evoked Ca2+
      signals were heterogeneously distributed along axons, with the largest and
      fastest responses appearing in hot spots on average approximately 5 microm apart.
      The spatial distribution of fluorescence responses was independent of the
      position of the focal plane, uncorrelated to basal dye fluorescence, and
      independent of dye concentration. Recordings using the low-affinity dye mag-fura
      2 and a Cs+-based intracellular solution revealed a similar pattern of hot spots
      in response to depolarisation, ruling out measurement artefacts or possible
      effects of inhomogeneous dye distribution in the generation of hot spots.
      Fluorescence responses to a short train of APs in hot spots decreased by 41-76 %
      after bath perfusion of omega-conotoxin MVIIC (5-6 microM), and by 17-65 % after
      application of omega-agatoxin IVA (500 nM). omega-Conotoxin GVIA (1 microM) had a
      variable, small effect (0-31 % inhibition), and nimodipine (5 microM) had none.
      Somatically recorded voltage-gated currents during depolarising pulses were
      unaffected in all cases. These data indicate that P/Q-type Ca2+ channels, and to
      a lesser extent N-type channels, are responsible for a large fraction of the
      [Ca2+] rise in axonalhot spots. [Ca2+] responses never failed during low
      frequency (<= 0.5 Hz) stimulation, indicating reliable AP propagation to the
      imaged sites. Axonal branching points coincided with a hot spot in approximately
      50 % of the cases. The spacing of presynaptic varicosities, as determined by a
      morphological analysis of Neurobiotin-filled axons, was approximately 10 times
      larger than the one measured for hot spots. The latter is comparable to the
      spacing reported for varicosities in mature animals. We discuss the nature of hot
      spots, considering as the most parsimonious explanation that they represent
      functional clusters of voltage-dependent Ca2+ channels, and possibly other [Ca2+]
      sources, marking the position of developing presynaptic terminals before the
      formation of en passant varicosities.

PMID- 10944169
TI  - Calcium signalling mediated by the 9 acetylcholine receptor in a cochlear cell
      line from the Immortomouse.
AB  - We have investigated the characteristics of the alpha9 acetylcholine receptor
      (alpha9AChR) expressed in hair cell precursors in an immortalized cell line UB/OC
      2 developed from the organ of Corti of the transgenic H-2Kb-tsA58 mouse (the
      Immortomouse) using both calcium imaging and whole-cell recording. Ratiometric
      measurements of fura-2 fluorescence revealed an increase of intracellular calcium
      concentration in cells when challenged with 10 uM ACh. The calcium increase was
      seen in 66 % of the cells grown at 39  degrees C in differentiated conditions. A
      smaller fraction (34 %) of cells grown at 33  degrees C in proliferative
      conditions responded. Caffeine (10 mM) elevated cell calcium. In the absence of
      caffeine, the majority of imaged cells responded only once to ACh. A small
      proportion (< 2 % of the total) responded with an increase in intracellular
      calcium to multiple ACh presentations. Pretreatment with caffeine inhibited all
      calcium responses to ACh. In whole-cell tight-seal recordings 10 uM ACh activated
      an inward, non-selective cation current. The reversal potential of the ACh
      activated inward current was dependent on the extracellular calcium concentration
      with an estimated PCa/PNa of 80 for the alpha9 receptor at physiological calcium
      levels. The data indicate that ACh activates a calcium-permeable channel
      alpha9AChR in UB/OC-2 cells and that the channel has a significantly higher
      calcium permeability than other AChRs. The results indicate that the alpha9AChR
      may be able to elevate intracellular calcium levels in hair cells both directly
      and via store release.

PMID- 10944170
TI  - Functional profile of the giant metacerebral neuron of Helix aspersa: temporal
      and spatial dynamics of electrical activity in situ.
AB  - 1. Understanding the biophysical properties of single neurons and how they
      process information is fundamental to understanding how the brain works. However,
      action potential initiation and the preceding integration of the synaptic signals
      in neuronal processes of individual cells are complex and difficult to understand
      in the absence of detailed, spatially resolved measurements. Multi-site optical
      recording with voltage-sensitive dyes from individual neurons in situ was used to
      provide these kinds of measurements. We analysed in detail the pattern of
      initiation and propagation of spikes evoked synaptically in an identified snail
      (Helix aspersa) neuron in situ. 2. Two main spike trigger zones were identified.
      The trigger zones were activated selectively by different sets of synaptic inputs
      which also produced different spike propagation patterns. 3. Synaptically evoked
      action potentials did not always invade all parts of the neuron. The conduction
      of the axonal spike was regularly blocked at particular locations on neuronal
      processes. 4. The propagating spikes in some axonal branches consistently
      reversed direction at certain branch points, a phenomenon known as reflection. 5.
      These experimental results, when linked to a computer model, could allow a new
      level of analysis of the electrical structure of single neurons.

PMID- 10944171
TI  - Store depletion and store-operated Ca2+ current in human prostate cancer LNCaP
      cells: involvement in apoptosis.
AB  - 1. In the present study, we investigated the mechanisms involved in the induction
      of apoptosis by the Ca2+-ATPase inhibitor thapsigargin (TG), in androgen
      sensitive human prostate cancer LNCaP cells. 2. Exposure of fura-2-loaded LNCaP
      cells to TG in the presence of extracellular calcium produced an increase in
      intracellular Ca2+, the first phase of which was associated with depletion of
      intracellular stores and the second one with consecutive extracellular Ca2+ entry
      through plasma membrane, store-operated Ca2+ channels (SOCs). 3. For the first
      time we have identified and characterized the SOC-mediated membrane current
      (Istore) in prostate cells using whole-cell, cell-attached, and perforated patch
      clamp techniques, combined with fura-2 microspectrofluorimetric and Ca2+-imaging
      measurements. 4. Istore in LNCaP cells lacked voltage-dependent gating and
      displayed an inwardly rectifying current-voltage relationship. The unitary
      conductance of SOCs with 80 mM Ca2+ as a charge carrier was estimated at 3.2 +/-
      0.4 pS. The channel has a high selectivity for Ca2+ over monovalent cations and
      is inhibited by Ni2+ (0.5-3 mM) and La3+ (1 microM). 5. Treatment of LNCaP cells
      with TG (0.1 microM) induced apoptosis as judged from morphological changes.
      Decreasing extracellular free Ca2+ to 200 nM or adding 0.5 mM Ni2+ enhanced TG
      induced apoptosis. 6. The ability of TG to induce apoptosis was not reduced by
      loading the cells with intracellular Ca2+ chelator (BAPTA-AM). 7. These results
      indicate that in androgen-sensitive prostate cancer cells the depletion of
      intracellular Ca2+ stores may trigger apoptosis but that there is no requirement
      for the activation of store-activated Ca2+ current and sustained Ca2+ entry in
      induction and development of programmed cell death.

PMID- 10944172
TI  - Diminished function and expression of the cardiac Na+-Ca2+ exchanger in diabetic
      rats: implication in Ca2+ overload.
AB  - 1. The present work was carried out in order to determine whether a decrease in
      cardiac Na+-Ca2+ exchanger (NCX) activity observed in diabetes is caused by a
      reduction in NCX protein and mRNA levels and to elucidate the significance of
      this decrease in alterations in [Ca2+]i homeostasis in diabetic cardiomyocytes.
      2. The NCX current was significantly reduced in ventricular myocytes freshly
      isolated from streptozotocin-induced diabetic rat hearts, and its current density
      was about 55 % of age-matched controls. 3. Diabetes resulted in a 30 % decrease
      in cardiac protein and mRNA levels of NCX1, a NCX isoform which is expressed at
      high levels in the heart. 4. The reduced NCX current and the decreased protein
      and mRNA levels of NCX1 in diabetes were prevented by insulin therapy. 5.
      Although both diastolic and peak systolic [Ca2+]i were not different between the
      two groups of myocytes, increasing external Ca2+ concentration to high levels
      greatly elevated diastolic [Ca2+]i in diabetic myocytes. Inhibition of NCX by
      reduction in extracellular Na+ by 50 % could produce a marked rise in diastolic
      [Ca2+]i in control myocytes in response to high Ca2+, as seen in diabetic
      myocytes. However, cyclopiazonic acid, an inhibitor of sarcoplasmic reticulum
      Ca2+ pump ATPase, did not modify the high Ca2+-induced changes in diastolic
      [Ca2+]i in either control or diabetic myocytes. 6. Only in papillary muscles from
      diabetic rats did the addition of high Ca2+ cause a marked rise in resting
      tension signifying a partial contracture that was possibly due to an increase in
      diastolic [Ca2+]i. 7. In conclusion, the diminished NCX function in diabetic
      myocytes shown in this study results in part from the decreased levels of cardiac
      NCX protein and mRNA. We suggest that this impaired NCX function may play an
      important role in alterations in Ca2+ handling when [Ca2+]i rises to pathological
      levels.

PMID- 10944173
TI  - Leptin activation of ATP-sensitive K+ (KATP) channels in rat CRI-G1 insulinoma
      cells involves disruption of the actin cytoskeleton.
AB  - 1. The role of the cytoskeleton in leptin-induced activation of ATP-sensitive K+
      (KATP) channels was examined in rat CRI-G1 insulin-secreting cells using patch
      clamp and fluorescence imaging techniques. 2. In whole cell recordings, dialysis
      with the actin filament stabiliser phalloidin (10 microM) prevented KATP channel
      activation by leptin. 3. Application of the actin filament destabilising agents
      deoxyribonuclease type 1 (DNase 1; 50 microg ml-1) or cytochalasin B (10 microM)
      to intact cells or inside-out membrane patches also increased KATP channel
      activity in a phalloidin-dependent manner. 4. The anti-microtubule agents
      nocodazole (10 microM) and colchicine (100 microM) had no effect on KATP channel
      activity. 5. Fluorescence staining of the cells with rhodamine-conjugated
      phalloidin revealed rapid disassembly of actin filaments by cytochalasin B and
      leptin, the latter action being prevented by the phosphoinositide 3 (PI 3)-kinase
      inhibitor LY 294002. 6. Activation of KATP channels by the PI 3-kinase product
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) was also prevented by
      phalloidin. This is consistent with the notion that leptin activates KATP
      channels in these cells by an increase in PtdIns(3,4,5)P3 or a similar 3
      phosphorylated phosphoinositol lipid, resulting in actin filament disruption.

PMID- 10944174
TI  - Tolbutamide stimulates exocytosis of glucagon by inhibition of a mitochondrial
      like ATP-sensitive K+ (KATP) conductance in rat pancreatic A-cells.
AB  - 1. Capacitance measurements were used to examine the effects of the sulphonylurea
      tolbutamide on Ca2+-dependent exocytosis in isolated glucagon-secreting rat
      pancreatic A-cells. 2. When applied extracellularly, tolbutamide stimulated
      depolarization-evoked exocytosis 4.2-fold without affecting the whole-cell Ca2+
      current. The concentration dependence of the stimulatory action was determined by
      intracellular application through the recording pipette. Tolbutamide produced a
      concentration-dependent increase in cell capacitance. Half-maximal stimulation
      was observed at 33 microM and the maximum stimulation corresponded to a 3.4-fold
      enhancement of exocytosis. 3. The stimulatory action of tolbutamide was dependent
      on protein kinase C activity. The action of tolbutamide was mimicked by the
      general K+ channel blockers TEA (10 mM) and quinine (10 microM). A similar
      stimulation was elicited by 5-hydroxydecanoate (5-HD; 10 microM), an inhibitor of
      mitochondrial ATP-sensitive K+ (KATP) channels. 4. Tolbutamide-stimulated, but
      not TEA-induced, exocytosis was antagonized by the K+ channel openers diazoxide,
      pinacidil and cromakalim. 5. Dissipating the transgranular K+ gradient with
      nigericin and valinomycin inhibited tolbutamide- and Ca2+-evoked exocytosis.
      Furthermore, tolbutamide- and Ca2+-induced exocytosis were abolished by the H+
      ionophore FCCP or by arresting the vacuolar (V-type) H+-ATPase with bafilomycin
      A1 or DCCD. Finally, ammonium chloride stimulated exocytosis to a similar extent
      to that obtained with tolbutamide. 6. We propose that during granular maturation,
      a granular V-type H+-ATPase pumps H+ into the secretory granule leading to the
      generation of a pH gradient across the granular membrane and the development of a
      positive voltage inside the granules. The pumping of H+ is facilitated by the
      concomitant exit of K+ through granular K+ channels with pharmacological
      properties similar to those of mitochondrial KATP channels. Release of granules
      that have been primed is then facilitated by the addition of K+ channel blockers.
      The resulting increase in membrane potential promotes exocytosis by unknown
      mechanisms, possibly involving granular alkalinization.

PMID- 10944175
TI  - Effects of amylin and other peptide hormones on Na+-K+ transport and
      contractility in rat skeletal muscle.
AB  - 1. In skeletal muscle, catecholamines and calcitonin gene-related peptide (CGRP)
      increase the content of cAMP, which mediates stimulation of the Na+-K+ pump.
      Amylin is structurally very similar to CGRP and also increases cAMP in muscle. 2.
      In isolated rat soleus and extensor digitorum longus muscle, amylin produced a
      rapid and marked decrease in intracellular Na+, which was maintained for several
      hours. In soleus, amylin was found to induce a 45 % stimulation of Na+ efflux, a
      43 % increase in 86Rb influx and a rise in intracellular K+. All these effects
      were abolished by ouabain, indicating that amylin produces acute stimulation of
      the Na+-K+ pump. 3. In contrast, neither the closely related peptides islet
      amyloid polypeptide (IAPP) and adrenomedullin nor other peptide hormones (C
      peptide, neuropeptide Y or substance P) produced any detectable change in
      intracellular Na+ or K+ uptake in soleus. 4. When contractility in soleus was
      inhibited by increasing extracellular K+ to 12.5 mM, amylin (10-8 M) and insulin
      (0.7 x 10-8 M) both induced partial recovery of force. These effects were
      additive, and in combination the two hormones elicited 63 and 80 % recovery of
      tetanic and twitch force, respectively. Higher concentrations produced even
      larger increases, and all effects were blocked by ouabain. 5. In buffer
      containing 12.5 mM K+, dibutyryl cAMP induced 71 % force recovery, which was
      increased by theophylline. The results indicate that amylin (like catecholamines,
      cAMP, CGRP and insulin) stimulates the Na+-K+ pump and thereby improves the
      contractility of depolarized skeletal muscle cells. This adds further support to
      the concept that the Na+-K+ pump is important for the maintenance of excitability
      in skeletal muscle.

PMID- 10944176
TI  - Twitch and tetanic force responses and longitudinal propagation of action
      potentials in skinned skeletal muscle fibres of the rat.
AB  - 1. Transverse electrical field stimulation (50 V cm-1, 2 ms duration) of
      mechanically skinned skeletal muscle fibres of the rat elicited twitch and
      tetanic force responses (36 +/- 4 and 83 +/- 4 % of maximum Ca2+-activated force,
      respectively; n = 23) closely resembling those in intact fibres. The responses
      were steeply dependent on the field strength and were eliminated by inclusion of
      10 microM tetrodotoxin (TTX) in the (sealed) transverse tubular (T-) system of
      the skinned fibres and by chronic depolarisation of the T-system. 2. Spontaneous
      twitch-like activity occurred sporadically in many fibres, producing near maximal
      force in some instances (mean time to peak: 190 +/- 40 ms; n = 4). Such responses
      propagated as a wave of contraction longitudinally along the fibre at a velocity
      of 13 +/- 3 mm s-1 (n = 7). These spontaneous contractions were also inhibited by
      inclusion of TTX in the T-system and by chronic depolarisation. 3. We examined
      whether the T-tubular network was interconnected longitudinally using fibre
      segments that were skinned for only approximately 2/3 of their length, leaving
      the remainder of each segment intact with its T-system open to the bathing
      solution. After such fibres were exposed to TTX (60 microM), the adjacent skinned
      region (with its T-system not open to the solution) became unresponsive to
      subsequent electrical stimulation in approximately 50 % of cases (7/15),
      indicating that TTX was able to diffuse longitudinally inside the fibre via the
      tubular network over hundreds of sarcomeres. 4. These experiments show that
      excitation-contraction coupling in mammalian muscle fibres involves action
      potential propagation both transversally and longitudinally within the tubular
      system. Longitudinal propagation of action potentials inside skeletal muscle
      fibres is likely to be an important safety mechanism for reducing conduction
      failure during fatigue and explains why, in developing skeletal muscle, the T
      system first develops as an internal longitudinal network.

PMID- 10944177
TI  - Swelling-activated cation channels mediate depolarization of rat cerebrovascular
      smooth muscle by hyposmolarity and intravascular pressure.
AB  - 1. Increases in intravascular pressure depolarize vascular smooth muscle cells.
      Based on the attenuating effects of Cl- channel antagonists, it has been
      suggested that swelling-activated Cl- channels may be integral to this response.
      Consequently, this study tested for the presence of a swelling-activated Cl-
      conductance in both intact rat cerebral arteries and isolated rat smooth muscle
      cells. 2. A 50 mosmol l-1 hyposmotic challenge (300 to 250 mosmol l-1)
      constricted rat cerebral arteries. This constriction contained all the salient
      features of a pressure-induced response including smooth muscle cell
      depolarization and a rise in intracellular Ca2+ that was blocked by voltage
      operated Ca2+ channel antagonists. The hyposmotically induced depolarization was
      attenuated by DIDS (300 microM) and tamoxifen (1 microM), a response consistent
      with the presence of a swelling-activated Cl- conductance. 3. A swelling
      activated current was identified in cerebral vascular smooth muscle cells. This
      current was sensitive to Cl- channel antagonists including DIDS (300 microM),
      tamoxifen (1 microM) and IAA-94 (100 microM). However, contrary to expectations,
      the reversal potential of this swelling-activated current shifted with the Na+
      equilibrium potential and not the Cl- equilibrium potential, indicating that the
      swelling-activated current was carried by cations and not anions. The swelling
      activated cation current was blocked by Gd3+, a cation channel antagonist. 4.
      Gd3+ also blocked both swelling- and pressure-induced depolarization of smooth
      muscle cells in intact cerebral arteries. 5. These findings suggest that swelling
      and pressure-induced depolarization arise from the activation of a cation
      conductance. This current is inhibited by DIDS, tamoxifen, IAA-94 and gadolinium.

PMID- 10944178
TI  - Regulation of pacemaker currents in interstitial cells of Cajal from murine small
      intestine by cyclic nucleotides.
AB  - 1. Electrical rhythmicity (slow waves) in gastrointestinal muscles (GI) is
      generated by interstitial cells of Cajal (ICC). Cultured ICC from the murine
      small intestine were studied with the patch-clamp technique to characterize
      regulation of pacemaker currents by cyclic nucleotides. Cyclic nucleotide
      agonists were also tested on intact strips of murine small intestine. 2. Nitric
      oxide donors slowed the frequency of pacemaker currents in a concentration
      dependent manner. These effects depended on cGMP formation and were reduced by 1H
      [1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The effects of nitric oxide
      donors were mimicked by membrane-permeable analogues of cGMP. The specific cGMP
      phosphodiesterase inhibitor zaprinast reduced the frequency of spontaneous
      pacemaker currents. 3. The cGMP-dependent effects on pacemaker currents were not
      affected by okadaic acid or KT-5823, an inhibitor of protein kinase G. 4.
      Forskolin, but not dideoxy forskolin, reduced the frequency of spontaneous
      pacemaker activity and activated a sustained outward current. The latter was
      likely to be due to ATP-dependent K+ channels because it was blocked by
      glibenclamide. 5. The effects of forskolin were not mimicked by membrane
      permeable cAMP analogues. A membrane-permeable inhibitor of protein kinase A,
      myristoylated PKA inhibitor, and the adenylyl cyclase inhibitor SQ-22536, had no
      effect on responses to forskolin. 6. Responses of intact muscles to cGMP and cAMP
      agonists were similar to the responses of pacemaker cells. Changes in resting
      membrane potential and slow wave amplitude, however, were noted in intact jejunal
      muscles that were not observed in ICC. Differences in responses may have been due
      to the effects of cyclic nucleotide agonists on smooth muscle cells that would
      sum with responses of ICC in intact jejunal muscle strips. 7. A cGMP-dependent
      mechanism regulates slow wave frequency, but this occurs through direct action of
      cGMP not via protein phosphorylation. Regulation of pacemaker currents by cAMP
      dependent mechanisms was not observed.

PMID- 10944179
TI  - Mechanisms underlying the reduced endothelium-dependent relaxation in human
      omental resistance artery in pre-eclampsia.
AB  - 1. In pre-eclampsia, a functional change occurs in the role played by endothelium
      derived nitric oxide (NO) in the regulation of smooth muscle contraction in
      resistance arteries. We investigated the underlying mechanism in human omental
      resistance arteries from normotensive pregnant and pre-eclamptic women in the
      presence of diclofenac (an inhibitor of cyclo-oxygenase). 2. In endothelium
      intact strips, the sensitivity to 9,11-epithio-11,12-methano-thromboxane A2
      (STA2) was significantly higher in pre-eclampsia, and this was not modified by
      either NG-nitro-L-arginine (L-NNA, an inhibitor of NO synthase) or removal of the
      endothelium. 3. Bradykinin and substance P each produced an endothelium-dependent
      relaxation of the STA2-induced contraction in both groups, although the
      relaxation was significantly smaller for pre-eclampsia. L-NNA markedly attenuated
      the endothelium-dependent relaxation in the normotensive pregnant group but not
      in the pre-eclamptic group. 4. In the presence of L-NNA, the relaxation induced
      by sodium nitroprusside (SNP) on the STA2 contraction was significantly smaller
      for pre-eclamptic than for normotensive pregnant women. 5. In endothelium-denuded
      strips, the relaxation induced by 8-para-chlorophenyl thio-guanosine-3', 5'
      cyclic monophosphate (8-pCPT-cGMP) on the STA2 contraction was significantly less
      for pre-eclampsia. 6. In beta-escin-skinned strips from both groups of women, 8
      pCPT-cGMP (1-10 microM) concentration-dependently attenuated the contraction
      induced by 0.5 microM Ca2+. However, its relaxing action was significantly weaker
      in pre-eclampsia. 7. It is suggested that the weaker responsivene to NO seen in
      strips from pre-eclamptic women may be partly due to a reduced smooth muscle
      responsiveness to cyclic GMP.

PMID- 10944180
TI  - Reflex secretion of proteins into submandibular saliva in conscious rats, before
      and after preganglionic sympathectomy.
AB  - 1. An indwelling catheter was placed in the left submandibular duct of rats,
      under pentobarbitone anaesthesia, and connected to an outflow cannula that
      emerged above the skull. 2. Saliva was collected from the outflow cannula in
      conscious rats, the same day after recovery from anaesthesia, under four
      different reflex conditions: grooming, heat exposure, rejection of a bitter
      tasting substance and feeding on softened chow, repeated in different orders. 3.
      Saliva flow was greatest for grooming and least for rejection. Protein
      concentrations were least with heat but much greater and similar for the other
      stimulations. Acinar peroxidase activity was high for feeding, intermediate for
      grooming and rejection, and again lowest with heat. Tubular tissue kallikrein
      activities were moderately low, being greatest with feeding and least with
      grooming. Secretory immunoglobulin A (SIgA) concentration was least with heat and
      similar for the other stimulations. 4. The next day, under pentobarbitone
      anaesthesia, the left preganglionic sympathetic trunk was sectioned (sympathetic
      decentralization) and, after recovery, the preceding stimulations were repeated.
      Flow of saliva showed little change, but protein and peroxidase concentrations
      and outputs decreased dramatically with grooming, rejection and feeding to levels
      similar to those with heat, which showed little change. Tissue kallikrein was
      lowered less dramatically, but the reductions in output were significant except
      with heat. Patterns of proteins resolved by electrophoresis changed for grooming,
      rejection and feeding and became similar to saliva from heat, which showed little
      change. No significant effects on SIgA concentrations occurred. 5. Gland weights
      from the sympathetically decentralized side were greater than from the intact
      side at the end of the experiments and histologically showed retention of acinar
      mucin. 6. Thus reflex sympathetic drive varied with the different stimulations;
      it was least during heat, but it had pronounced effects on acinar secretion of
      proteins during the other stimulations. At the same time this sympathetic drive
      had less impact on tissue kallikrein secretion from tubules and had little
      influence on flow or the concentration of SIgA secreted.

PMID- 10944181
TI  - Time course of post-excitatory effects separates afferent human C fibre classes.
AB  - 1. To study post-excitatory changes of conduction velocity, action potentials
      were recorded from 132 unmyelinated nerve fibres (C fibres) in cutaneous
      fascicles of the peroneal nerve using microneurography in healthy human subjects.
      The 'marking' technique was used to assess responsiveness to mechanical and heat
      stimuli or sympathetic reflex provocation. 2. C fibres were classified into three
      major classes: mechano-responsive afferent (n = 76), mechano-insensitive afferent
      (n = 48) and sympathetic efferent C fibres (n = 8). 3. During regular stimulation
      at 0.25 Hz, conditioning pulses were intermittently interposed. Changes of
      conduction velocity were assessed for different numbers of conditioning impulses
      and varying interstimulus intervals (ISIs). For all three fibre classes the
      latency shift following conditioning pulses at an ISI of 1000 ms increased
      linearly with their number (n = 1, 2 and 4). However, the absolute degree of
      conduction velocity slowing was much higher in the 32 mechano-insensitive fibres
      as compared with 56 mechano-responsive or 8 sympathetic fibres. 4. Single
      additional pulses were interposed at different ISIs from 20 to 2000 ms. For 20
      mechano-responsive fibres conduction velocity slowing increased with decreasing
      ISI (subnormal phase). In contrast, for 16 mechano-insensitive C fibres the
      conduction velocity slowing decreased with shorter ISIs, and at values lower than
      417 +/- 49 ms (mean +/- s.e.m.) the conduction velocity of the conditioned action
      potential was faster than before (conduction velocity speeding). This supernormal
      phase had its maximum at 69 +/- 10 ms. 5. In this study we provide, for the first
      time, direct evidence of relative supernormal conduction in human mechano
      insensitive C fibres. The implications for temporal coding in different afferent
      C fibre classes are discussed.

PMID- 10944182
TI  - Cardiovascular responses to static exercise in patients with Brown-Sequard
      syndrome.
AB  - 1. The purpose of this study was to determine the contributions of central
      command and the exercise pressor reflex in regulating the cardiovascular response
      to static exercise in patients with Brown-Sequard syndrome. In this rare
      condition, a hemisection of the spinal cord typically leaves one side of the body
      with diminished sensation and normal motor function and the other side with
      diminished motor function and normal sensation. 2. Four, otherwise healthy,
      patients with Brown-Sequard syndrome and varying degrees of motor and sensory
      dysfunction were studied during four isometric knee extension protocols involving
      both voluntary contraction and electrically stimulated contractions of each leg.
      Heart rate, blood pressure, force production and ratings of perceived exertion
      were measured during all conditions. Measurements were also made during post
      contraction thigh cuff occlusion and during a cold pressor test. 3. With the
      exception of electrical stimulation of the leg with a sensory deficit, protocols
      yielded increases in heart rate and blood pressure. Cuff occlusion sustained
      blood pressure above resting levels only when the leg had intact sensation. 4.
      While voluntary contraction (or attempted contraction) of the leg with a motor
      deficit produced the lowest force, it produced the highest ratings of perceived
      exertion coupled with the greatest elevations in heart rate and blood pressure.
      5. These data show that the magnitude of the heart rate and blood pressure
      responses in these patients was greatly affected by an increased central command;
      however, there were marked cardiovascular responses due to activation of the
      exercise pressor reflex in the absence of central command.

PMID- 10944184
TI  - A meanfield approach to the thermodynamics of a protein-solvent system with
      application to the oligomerization of the tumor suppressor p53.
AB  - The thermodynamic stability and oligomerization status of the tumor suppressor
      p53 tetramerization domain have been studied experimentally and theoretically. A
      series of hydrophilic mutations at Met-340 and Leu-344 of human p53 were designed
      to disrupt the hydrophobic dimer-dimer interface of the tetrameric
      oligomerization domain of p53 (residues 325-355). Meanfield calculations of the
      free energy of the solvated mutants as a function of interdimer distance were
      compared with experimental data on the thermal stability and oligomeric state
      (tetramer, dimer, or equilibrium mixture of both) of each mutant. The
      calculations predicted a decreasing stability and oligomeric state for the
      following amino acids at residue 340: Met (tetramer) > Ser Asp, His, Gln, > Glu,
      Lys (dimer), whereas the experimental results showed the following order: Met
      (tetramer) > Ser > Gln > His, Lys > Asp, Glu (dimers). For residue 344, the
      calculated trend was Leu (tetramer) > Ala > Arg, Gln, Lys (dimer), and the
      experimental trend was Leu (tetramer) > Ala, Arg, Gln, Lys (dimer). The
      discrepancy for the lysine side chain at residue 340 is attributed to the dual
      nature of lysine, both hydrophobic and charged. The incorrect prediction of
      stability of the mutant with Asp at residue 340 is attributed to the fact that
      within the meanfield approach, we use the wild-type backbone configuration for
      all mutants, but low melting temperatures suggest a softening of the alpha
      helices at the dimer-dimer interface. Overall, this initial application of
      meanfield theory toward a protein-solvent system is encouraging for the
      application of the theoretical model to more complex systems.

PMID- 10944183
TI  - Connexin expression in electrically coupled postnatal rat brain neurons.
AB  - Electrical coupling by gap junctions is an important form of cell-to-cell
      communication in early brain development. Whereas glial cells remain electrically
      coupled at postnatal stages, adult vertebrate neurons were thought to communicate
      mainly via chemical synapses. There is now accumulating evidence that in certain
      neuronal cell populations the capacity for electrical signaling by gap junction
      channels is still present in the adult. Here we identified electrically coupled
      pairs of neurons between postnatal days 12 and 18 in rat visual cortex,
      somatosensory cortex, and hippocampus. Notably, coupling was found both between
      pairs of inhibitory neurons and between inhibitory and excitatory neurons.
      Molecular analysis by single-cell reverse transcription-PCR revealed a
      differential expression pattern of connexins in these identified neurons.

PMID- 10944185
TI  - Designed protein tetramer zipped together with a hydrophobic Alzheimer homology:
      a structural clue to amyloid assembly.
AB  - Limited solubility and precipitation of amyloidogenic sequences such as the
      Alzheimer peptide (beta-AP) are major obstacles to a molecular understanding of
      protein fibrillation and deposition processes. Here we have circumvented the
      solubility problem by stepwise engineering a beta-AP homology into a soluble
      scaffold, the monomeric protein S6. The S6 construct with the highest beta-AP
      homology crystallizes as a tetramer that is linked by the beta-AP residues
      forming intermolecular antiparallel beta-sheets. This construct also shows
      increased coil aggregation during refolding, and a 14-mer peptide encompassing
      the engineered sequence forms fibrils. Mutational analysis shows that
      intermolecular association is linked to the overall hydrophobicity of the sticky
      sequence and implies the existence of "structural gatekeepers" in the wild-type
      protein, that is, charged side chains that prevent aggregation by interrupting
      contiguous stretches of hydrophobic residues in the primary sequence.

PMID- 10944186
TI  - Directed evolution of a (beta alpha)8-barrel enzyme to catalyze related reactions
      in two different metabolic pathways.
AB  - Enzymes participating in different metabolic pathways often have similar
      catalytic mechanisms and structures, suggesting their evolution from a common
      ancestral precursor enzyme. We sought to create a precursor-like enzyme for N'
      [(5'-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide
      (ProFAR) isomerase (HisA; EC ) and phosphoribosylanthranilate (PRA) isomerase
      (TrpF; EC ), which catalyze similar reactions in the biosynthesis of the amino
      acids histidine and tryptophan and have a similar (betaalpha)(8)-barrel
      structure. Using random mutagenesis and selection, we generated several HisA
      variants that catalyze the TrpF reaction both in vivo and in vitro, and one of
      these variants retained significant HisA activity. A more detailed analysis
      revealed that a single amino acid exchange could establish TrpF activity on the
      HisA scaffold. These findings suggest that HisA and TrpF may have evolved from an
      ancestral enzyme of broader substrate specificity and underscore that
      (betaalpha)(8)-barrel enzymes are very suitable for the design of new catalytic
      activities.

PMID- 10944187
TI  - Identification of a renal-specific oxido-reductase in newborn diabetic mice.
AB  - Aldose reductase (ALR2), a NADPH-dependent aldo-keto reductase (AKR), is widely
      distributed in mammalian tissues and has been implicated in complications of
      diabetes, including diabetic nephropathy. To identify a renal-specific reductase
      belonging to the AKR family, representational difference analyses of cDNA from
      diabetic mouse kidney were performed. A full-length cDNA with an ORF of 855 nt
      and yielding a approximately 1.5-kb mRNA transcript was isolated from a mouse
      kidney library. Human and rat homologues also were isolated, and they had
      approximately 91% and approximately 97% amino acid identity with mouse protein.
      In vitro translation of the cDNA yielded a protein product of approximately 33
      kDa. Northern and Western blot analyses, using the cDNA and antirecombinant
      protein antibody, revealed its expression exclusively confined to the kidney.
      Like ALR2, the expression was up-regulated in diabetic kidneys. Its mRNA and
      protein expression was restricted to renal proximal tubules. The gene neither
      codistributed with Tamm-Horsfall protein nor aquaporin-2. The deduced protein
      sequence revealed an AKR-3 motif located near the N terminus, unlike the other
      AKR family members where it is confined to the C terminus. Fluorescence quenching
      and reactive blue agarose chromatography studies revealed that it binds to NADPH
      with high affinity (K(dNADPH) = 66.9 +/- 2.3 nM). This binding domain is a
      tetrapeptide (Met-Ala-Lys-Ser) located within the AKR-3 motif that is similar to
      the other AKR members. The identified protein is designated as RSOR because it is
      renal-specific with properties of an oxido-reductase, and like ALR2 it may be
      relevant in the renal complications of diabetes mellitus.

PMID- 10944188
TI  - Functional and physiological consequences of genetic variation at phosphoglucose
      isomerase: heat shock protein expression is related to enzyme genotype in a
      montane beetle.
AB  - Allele frequency variation at the phosphoglucose isomerase (PGI) locus in
      Californian populations of the beetle Chrysomela aeneicollis suggests that PGI
      may be undergoing natural selection. We quantified (i) apparent Michaelis-Menten
      constant (K(m)) of fructose 6-phosphate at different temperatures and (ii)
      thermal stability for three common PGI genotypes (1-1, 1-4, and 4-4). We also
      measured air temperature (T(a)) and beetle body temperature (T(b)) in three
      montane drainages in the Sierra Nevada, California. Finally, we measured 70-kDa
      heat shock protein (Hsp70) expression in field-collected and laboratory
      acclimated beetles. We found that PGI allele 1 predominated in the northernmost
      drainage, Rock Creek (RC), which was also significantly cooler than the
      southernmost drainage, Big Pine Creek (BPC), where PGI allele 4 predominated.
      Allele frequencies and air temperatures were intermediate in the middle drainage,
      Bishop Creek (BC). Differences among genotypes in K(m) (1-1 > 1-4 > 4-4) and
      thermal stability (4-4 > 1-4 > 1-1) followed a pattern consistent with
      temperature adaptation. In nature, T(b) was closely related to T(a). Hsp70
      expression in adult beetles decreased with elevation and differed among drainages
      (BPC > BC > RC). After laboratory acclimation (8 days, 20 degrees C day, 4
      degrees C night) and heat shock (4 h, 28-36 degrees C), Hsp70 expression was
      greater for RC than BPC beetles. In RC, field-collected beetles homozygous for
      PGI 1-1 had higher Hsp70 levels than heterozygotes or a 4-4 homozygote. These
      results reveal functional and physiological differences among PGI genotypes,
      which suggest that montane populations of this beetle are locally adapted to
      temperature.

PMID- 10944189
TI  - The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce
      mitotic defects and genomic instability by uncoupling centrosome duplication from
      the cell division cycle.
AB  - Loss of genomic integrity is a defining feature of many human malignancies,
      including human papillomavirus (HPV)-associated preinvasive and invasive genital
      squamous lesions. Here we show that aberrant mitotic spindle pole formation
      caused by abnormal centrosome numbers represents an important mechanism in
      accounting for numeric chromosomal alterations in HPV-associated carcinogenesis.
      Similar to what we found in histopathological specimens, HPV-16 E6 and E7
      oncoproteins cooperate to induce abnormal centrosome numbers, aberrant mitotic
      spindle pole formation, and genomic instability. The low-risk HPV-6 E6 and E7
      proteins did not induce such abnormalities. Whereas the HPV-16 E6 oncoprotein has
      no immediate effects on centrosome numbers, HPV-16 E7 rapidly induces abnormal
      centrosome duplication. Thus our results suggest a model whereby HPV-16 E7
      induces centrosome-related mitotic disturbances that are potentiated by HPV-16
      E6.

PMID- 10944190
TI  - Molecular characterization and assembly of the needle complex of the Salmonella
      typhimurium type III protein secretion system.
AB  - Many bacterial pathogens of plants and animals have evolved a specialized protein
      secretion system termed type III to deliver bacterial proteins into host cells.
      These proteins stimulate or interfere with host cellular functions for the
      pathogen's benefit. The Salmonella typhimurium pathogenicity island 1 encodes one
      of these systems that mediates this bacterium's ability to enter nonphagocytic
      cells. Several components of this type III secretion system are organized in a
      supramolecular structure termed the needle complex. This structure is made of
      discrete substructures including a base that spans both membranes and a needle
      like projection that extends outward from the bacterial surface. We demonstrate
      here that the type III secretion export apparatus is required for the assembly of
      the needle substructure but is dispensable for the assembly of the base. We show
      that the length of the needle segment is determined by the type III secretion
      associated protein InvJ. We report that InvG, PrgH, and PrgK constitute the base
      and that PrgI is the main component of the needle of the type III secretion
      complex. PrgI homologs are present in type III secretion systems from bacteria
      pathogenic for animals but are absent from bacteria pathogenic for plants. We
      hypothesize that the needle component may establish the specificity of type III
      secretion systems in delivering proteins into either plant or animal cells.

PMID- 10944191
TI  - Photochemically induced nuclear spin polarization in reaction centers of
      photosystem II observed by 13C-solid-state NMR reveals a strongly asymmetric
      electronic structure of the P680(.+) primary donor chlorophyll.
AB  - We report (13)C magic angle spinning NMR observation of photochemically induced
      dynamic nuclear spin polarization (photo-CIDNP) in the reaction center (RC) of
      photosystem II (PS2). The light-enhanced NMR signals of the natural abundance
      (13)C provide information on the electronic structure of the primary electron
      donor P(680) (chlorophyll a molecules absorbing around 680 nm) and on the p(z)
      spin density pattern in its oxidized form, P(680)(.+). Most centerband signals
      can be attributed to a single chlorophyll a (Chl a) cofactor that has little
      interaction with other pigments. The chemical shift anisotropy of the most
      intense signals is characteristic for aromatic carbon atoms. The data reveal a
      pronounced asymmetry of the electronic spin density distribution within the
      P(680)(.+). PS2 shows only a single broad and intense emissive signal, which is
      assigned to both the C-10 and C-15 methine carbon atoms. The spin density appears
      shifted toward ring III. This shift is remarkable, because, for monomeric Chl a
      radical cations in solution, the region of highest spin density is around ring
      II. It leads to a first hypothesis as to how the planet can provide itself with
      the chemical potential to split water and generate an oxygen atmosphere using the
      Chl a macroaromatic cycle. A local electrostatic field close to ring III can
      polarize the electronic charge and associated spin density and increase the redox
      potential of P(680) by stabilizing the highest occupied molecular orbital,
      without a major change of color. This field could be produced, e.g., by
      protonation of the keto group of ring V. Finally, the radical cation electronic
      structure in PS2 is different from that in the bacterial RC, which shows at least
      four emissive centerbands, indicating a symmetric spin density distribution over
      the entire bacteriochlorophyll macrocycle.

PMID- 10944192
TI  - Cyclin-dependent kinases as a therapeutic target for stroke.
AB  - Cyclin-dependent kinases (CDKs) are commonly known to regulate cell
      proliferation. However, previous reports suggest that in cultured postmitotic
      neurons, activation of CDKs is a signal for death rather than cell division. We
      determined whether CDK activation occurs in mature adult neurons during focal
      stroke in vivo and whether this signal was required for neuronal death after
      reperfusion injury. Cdk4/cyclin D1 levels and phosphorylation of its substrate
      retinoblastoma protein (pRb) increase after stroke. Deregulated levels of E2F1, a
      transcription factor regulated by pRb, are also observed. Administration of a CDK
      inhibitor blocks pRb phosphorylation and the increase in E2F1 levels and
      dramatically reduces neuronal death by 80%. These results indicate that CDKs are
      an important therapeutic target for the treatment of reperfusion injury after
      ischemia.

PMID- 10944193
TI  - Inhibition of the ubiquitin-proteasome system in Alzheimer's disease.
AB  - Alzheimer's disease is the most common cause of dementia in the elderly. Although
      several genetic defects have been identified in patients with a family history of
      this disease, the majority of cases involve individuals with no known genetic
      predisposition. A mutant form of ubiquitin, termed Ub(+1), has been selectively
      observed in the brains of Alzheimer's patients, including those with nonfamilial
      Alzheimer's disease, but it has been unclear why Ub(+1) expression should be
      deleterious. Here we show that Ub(+1) is an efficient substrate for
      polyubiquitination in vitro and in transfected human cells. The resulting
      polyubiquitin chains are refractory to disassembly by deubiquitinating enzymes
      and potently inhibit the degradation of a polyubiquitinated substrate by purified
      26S proteasomes. Thus, expression of Ub(+1) in aging brain could result in
      dominant inhibition of the Ub-proteasome system, leading to neuropathologic
      consequences.

PMID- 10944194
TI  - Molecular basis of lutropin recognition by the mannose/GalNAc-4-SO4 receptor.
AB  - The circulatory half-life of the glycoprotein hormone lutropin (LH) is precisely
      regulated by the mannose (Man)/GalNAc-4-SO(4) receptor expressed in hepatic
      endothelial cells. Rapid clearance from the circulation contributes to the
      episodic rise and fall of LH levels that is essential for maximal stimulation of
      the G protein-coupled LH receptor. We have defined two molecular forms of the
      Man/GalNAc-4-SO(4) receptor that differ in ligand specificity, cell and tissue
      expression, and function. The form expressed by hepatic endothelial cells binds
      GalNAc-4-SO(4)-bearing ligands and regulates hormone circulatory half-life,
      whereas the form expressed by macrophages binds Man-bearing ligands and may play
      a role in innate immunity. We demonstrate that the GalNAc-4-SO(4)-specific form
      in hepatic endothelial cells is dimeric whereas the Man-specific form in lung
      macrophages is monomeric, accounting for the different ligand specificities of
      the receptor expressed in these tissues. Two cysteine-rich domains, each of which
      binds a single GalNAc-4-SO(4), are required to form stable complexes with LH. The
      kinetics of LH binding by the GalNAc-4-SO(4)-specific form of the receptor in
      conjunction with its rate of internalization from the cell surface make it likely
      that only two of the four terminal GalNAc-4-SO(4) moieties present on native LH
      are engaged before receptor internalization. As a result, the rate of hormone
      clearance will remain constant over a wide range of LH concentrations and will
      not be sensitive to variations in the number of terminal GalNAc-4-SO(4) moieties
      as long as two or more are present on multiple oligosaccharides.

PMID- 10944195
TI  - Redox state is a central modulator of the balance between self-renewal and
      differentiation in a dividing glial precursor cell.
AB  - We have discovered that intracellular redox state appears to be a necessary and
      sufficient modulator of the balance between self-renewal and differentiation in
      dividing oligodendrocyte-type-2 astrocyte progenitor cells. The intracellular
      redox state of freshly isolated progenitors allows prospective isolation of cells
      with different self-renewal characteristics. Redox state is itself modulated by
      cell-extrinsic signaling molecules that alter the balance between self-renewal
      and differentiation: growth factors that promote self-renewal cause progenitors
      to become more reduced, while signaling molecules that promote differentiation
      cause progenitors to become more oxidized. Moreover, pharmacological antagonists
      of the redox effects of these cell-extrinsic signaling molecules antagonize their
      effects on self-renewal and differentiation, indicating that cell-extrinsic
      signaling molecules that modulate this balance converge on redox modulation as a
      critical component of their effector mechanism.

PMID- 10944197
TI  - Global warming in the twenty-first century: an alternative scenario.
AB  - A common view is that the current global warming rate will continue or
      accelerate. But we argue that rapid warming in recent decades has been driven
      mainly by non-CO(2) greenhouse gases (GHGs), such as chlorofluorocarbons, CH(4),
      and N(2)O, not by the products of fossil fuel burning, CO(2) and aerosols, the
      positive and negative climate forcings of which are partially offsetting. The
      growth rate of non-CO(2) GHGs has declined in the past decade. If sources of
      CH(4) and O(3) precursors were reduced in the future, the change in climate
      forcing by non-CO(2) GHGs in the next 50 years could be near zero. Combined with
      a reduction of black carbon emissions and plausible success in slowing CO(2)
      emissions, this reduction of non-CO(2) GHGs could lead to a decline in the rate
      of global warming, reducing the danger of dramatic climate change. Such a focus
      on air pollution has practical benefits that unite the interests of developed and
      developing countries. However, assessment of ongoing and future climate change
      requires composition-specific long-term global monitoring of aerosol properties.

PMID- 10944196
TI  - Altered expression of the ToxR-regulated porins OmpU and OmpT diminishes Vibrio
      cholerae bile resistance, virulence factor expression, and intestinal
      colonization.
AB  - The transmembrane transcriptional activators ToxR and TcpP modulate expression of
      Vibrio cholerae virulence factors by exerting control over toxT, which encodes
      the cytoplasmic transcriptional activator of the ctx, tcp, and acf virulence
      genes. However, ToxR, independently of TcpP and ToxT, activates and represses
      transcription of the genes encoding two outer-membrane porins, OmpU and OmpT. To
      determine the role of ToxR-dependent porin regulation in V. cholerae
      pathogenesis, the ToxR-activated ompU promoter was used to drive ompT
      transcription in a strain lacking OmpU. Likewise, the ToxR-repressed ompT
      promoter was used to drive ompU transcription in a strain lacking both ToxR and
      OmpT. This strategy allowed the generation of a toxR(+) strain that expresses
      OmpT in place of OmpU, and a toxR(-) strain that expresses OmpU in place of OmpT.
      Growth rates in the presence of bile salts and other anionic detergents were
      retarded for the toxR(+) V. cholerae expressing OmpT in place of OmpU, but
      increased in toxR(-) V. cholerae expressing OmpU in place of OmpT. Additionally,
      the toxR(+) V. cholerae expressing OmpT in place of OmpU expressed less cholera
      toxin and toxin-coregulated pilus, and this effect was shown to be caused by
      reduced toxT transcription in this strain. Finally, the toxR(+) V. cholerae
      expressing OmpT in place of OmpU was approximately 100-fold reduced in its
      ability to colonize the infant-mouse intestine. Our results indicate that ToxR
      dependent modulation of the outer membrane porins OmpU and OmpT is critical for
      V. cholerae bile resistance, virulence factor expression, and intestinal
      colonization.

PMID- 10944198
TI  - A cellular defense pathway regulating transcription through poly(ADP
      ribosyl)ation in response to DNA damage.
AB  - DNA damage is known to trigger key cellular defense pathways such as those
      involved in DNA repair. Here we provide evidence for a previously unrecognized
      pathway regulating transcription in response to DNA damage and show that this
      regulation is mediated by the abundant nuclear enzyme poly(ADP-ribose)
      polymerase. We found that poly(ADP-ribose) polymerase reduced the rate of
      transcription elongation by RNA polymerase II, suggesting that poly(ADP-ribose)
      polymerase negatively regulates transcription, possibly through the formation of
      poly(ADP-ribose) polymerase-RNA complexes. In damaged cells, poly(ADP-ribose)
      polymerase binds to DNA breaks and automodifies itself in the presence of NAD(+),
      resulting in poly(ADP-ribose) polymerase inactivation. We found that
      automodification of poly(ADP-ribose) polymerase in response to DNA damage
      resulted in the up-regulation of transcription, presumably because automodified
      poly(ADP-ribose) polymerase molecules were released from transcripts, thereby
      relieving the block on transcription. Because agents that damage DNA damage RNA
      as well, up-regulation of RNA synthesis in response to DNA damage may provide
      cells with a mechanism to compensate for the loss of damaged transcripts and may
      be critical for cell survival after exposure to DNA-damaging agents.

PMID- 10944199
TI  - Contact with fibrillar collagen inhibits melanoma cell proliferation by up
      regulating p27KIP1.
AB  - It is known that the extracellular matrix regulates normal cell proliferation,
      and it is assumed that anchorage-independent malignant cells escape this
      regulatory function. Here we demonstrate that human M24met melanoma cells remain
      responsive to growth regulatory signals that result from contact with type I
      collagen and that the effect on proliferation depends on the physical structure
      of the collagen. On polymerized fibrillar collagen, M24met cells are growth
      arrested at the G(1)/S checkpoint and maintain high levels of p27(KIP1) mRNA and
      protein. In contrast, on nonfibrillar (denatured) collagen, the cells enter the
      cell cycle, and p27(KIP1) is down-regulated. These growth regulatory effects
      involve contact between type I collagen and the collagen-binding integrin
      alpha(2)beta(1), which appears restricted in the presence of fibrillar collagen.
      Thus melanoma cells remain sensitive to negative growth regulatory signals
      originating from fibrillar collagen, and the proteolytic degradation of fibrils
      is a mechanism allowing tumor cells to escape these restrictive signals.

PMID- 10944200
TI  - TOM1, an Arabidopsis gene required for efficient multiplication of a tobamovirus,
      encodes a putative transmembrane protein.
AB  - Host-encoded factors play an important role in virus multiplication, acting in
      concert with virus-encoded factors. However, information regarding the host
      factors involved in this process is limited. Here we report the map-based cloning
      of an Arabidopsis thaliana gene, TOM1, which is necessary for the efficient
      multiplication of tobamoviruses, positive-strand RNA viruses infecting a wide
      variety of plants. The TOM1 mRNA is suggested to encode a 291-aa polypeptide that
      is predicted to be a multipass transmembrane protein. The Sos recruitment assay
      supported the hypothesis that TOM1 is associated with membranes, and in addition,
      that TOM1 interacts with the helicase domain of tobamovirus-encoded replication
      proteins. Taken into account that the tobamovirus replication complex is
      associated with membranes, we propose that TOM1 participates in the in vivo
      formation of the replication complex by serving as a membrane anchor.

PMID- 10944202
TI  - Building a dictionary for genomes: identification of presumptive regulatory sites
      by statistical analysis.
AB  - The availability of complete genome sequences and mRNA expression data for all
      genes creates new opportunities and challenges for identifying DNA sequence
      motifs that control gene expression. An algorithm, "MobyDick," is presented that
      decomposes a set of DNA sequences into the most probable dictionary of motifs or
      words. This method is applicable to any set of DNA sequences: for example, all
      upstream regions in a genome or all genes expressed under certain conditions.
      Identification of words is based on a probabilistic segmentation model in which
      the significance of longer words is deduced from the frequency of shorter ones of
      various lengths, eliminating the need for a separate set of reference data to
      define probabilities. We have built a dictionary with 1,200 words for the 6, 000
      upstream regulatory regions in the yeast genome; the 500 most significant words
      (some with as few as 10 copies in all of the upstream regions) match 114 of 443
      experimentally determined sites (a significance level of 18 standard deviations).
      When analyzing all of the genes up-regulated during sporulation as a group, we
      find many motifs in addition to the few previously identified by analyzing the
      subclusters individually to the expression subclusters. Applying MobyDick to the
      genes derepressed when the general repressor Tup1 is deleted, we find known as
      well as putative binding sites for its regulatory partners.

PMID- 10944204
TI  - Reliability of axonal propagation: the spike doesn't stop here.

PMID- 10944203
TI  - Growth differentiation factor-9 stimulates progesterone synthesis in granulosa
      cells via a prostaglandin E2/EP2 receptor pathway.
AB  - Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the
      transforming growth factor beta superfamily, progesterone receptor,
      cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin E(2) (PGE(2)) receptor
      (EP2; Ptgerep2) are required for fertility in female but not male mice. To define
      the interrelationship of these factors, we used a preovulatory granulosa cell
      culture system in which we added recombinant GDF-9, prostaglandins, prostaglandin
      receptor agonists, or cyclooxygenase inhibitors. GDF-9 stimulated Cox2 mRNA
      within 2 h, and PGE(2) within 6 h; however, progesterone was not increased until
      12 h after addition of GDF-9. This suggested that Cox2 is a direct downstream
      target of GDF-9 but that progesterone synthesis required an intermediate. To
      determine whether prostaglandin synthesis was required for progesterone
      production, we analyzed the effects of PGE(2) and cyclooxygenase inhibitors on
      this process. PGE(2) can stimulate progesterone synthesis by itself, although
      less effectively than GDF-9 (3-fold vs. 6-fold increase over 24 h, respectively).
      Furthermore, indomethacin or NS-398, inhibitors of Cox2, block basal and GDF-9
      stimulated progesterone synthesis. However, addition of PGE(2) to cultures
      containing both GDF-9 and NS-398 overrides the NS-398 block in progesterone
      synthesis. To further define the PGE(2)-dependent pathway, we show that
      butaprost, a specific EP2 agonist, stimulates progesterone synthesis and
      overrides the NS-398 block. In addition, GDF-9 stimulates EP2 mRNA synthesis by a
      prostaglandin- and progesterone-independent pathway. Thus, GDF-9 induces an EP2
      signal transduction pathway which appears to be required for progesterone
      synthesis in cumulus granulosa cells. These studies further demonstrate the
      importance of oocyte-somatic cell interactions in female reproduction.

PMID- 10944205
TI  - Resolving the relationships of resolving enzymes.

PMID- 10944206
TI  - A large step for myosin.

PMID- 10944207
TI  - Ions, cell volume, and apoptosis.

PMID- 10944208
TI  - Heritability at the ecosystem level.

PMID- 10944209
TI  - Site-directed ligand discovery.
AB  - We report a strategy (called "tethering") to discover low molecular weight
      ligands ( approximately 250 Da) that bind weakly to targeted sites on proteins
      through an intermediary disulfide tether. A native or engineered cysteine in a
      protein is allowed to react reversibly with a small library of disulfide
      containing molecules ( approximately 1,200 compounds) at concentrations typically
      used in drug screening (10 to 200 microM). The cysteine-captured ligands, which
      are readily identified by MS, are among the most stable complexes, even though in
      the absence of the covalent tether the ligands may bind very weakly. This method
      was applied to generate a potent inhibitor for thymidylate synthase, an essential
      enzyme in pyrimidine metabolism with therapeutic applications in cancer and
      infectious diseases. The affinity of the untethered ligand (K(i) approximately 1
      mM) was improved 3,000-fold by synthesis of a small set of analogs with the aid
      of crystallographic structures of the tethered complex. Such site-directed ligand
      discovery allows one to nucleate drug design from a spatially targeted lead
      fragment.

PMID- 10944210
TI  - Structure-based design of an osteoclast-selective, nonpeptide src homology 2
      inhibitor with in vivo antiresorptive activity.
AB  - Targeted disruption of the pp60(src) (Src) gene has implicated this tyrosine
      kinase in osteoclast-mediated bone resorption and as a therapeutic target for the
      treatment of osteoporosis and other bone-related diseases. Herein we describe the
      discovery of a nonpeptide inhibitor (AP22408) of Src that demonstrates in vivo
      antiresorptive activity. Based on a cocrystal structure of the noncatalytic Src
      homology 2 (SH2) domain of Src complexed with citrate [in the phosphotyrosine
      (pTyr) binding pocket], we designed 3',4'-diphosphonophenylalanine (Dpp) as a
      pTyr mimic. In addition to its design to bind Src SH2, the Dpp moiety exhibits
      bone-targeting properties that confer osteoclast selectivity, hence minimizing
      possible undesired effects on other cells that have Src-dependent activities. The
      chemical structure AP22408 also illustrates a bicyclic template to replace the
      post-pTyr sequence of cognate Src SH2 phosphopeptides such as Ac-pTyr-Glu-Glu-Ile
      (1). An x-ray structure of AP22408 complexed with Lck (S164C) SH2 confirmed
      molecular interactions of both the Dpp and bicyclic template of AP22408 as
      predicted from molecular modeling. Relative to the cognate phosphopeptide,
      AP22408 exhibits significantly increased Src SH2 binding affinity (IC(50) = 0.30
      microM for AP22408 and 5.5 microM for 1). Furthermore, AP22408 inhibits rabbit
      osteoclast-mediated resorption of dentine in a cellular assay, exhibits bone
      targeting properties based on a hydroxyapatite adsorption assay, and demonstrates
      in vivo antiresorptive activity in a parathyroid hormone-induced rat model.

PMID- 10944211
TI  - Computational evidence in favor of a two-state, two-mode model of the retinal
      chromophore photoisomerization.
AB  - In this paper we use ab initio multiconfigurational second-order perturbation
      theory to establish the intrinsic photoisomerization path model of retinal
      chromophores. This is accomplished by computing the ground state (S(0)) and the
      first two singlet excited-state (S(1), S(2)) energies along the rigorously
      determined photoisomerization coordinate of the rhodopsin chromophore model 4-cis
      gamma-methylnona-2,4,6,8-tetraeniminium cation and the bacteriorhodopsin
      chromophore model all-trans-hepta-2,4, 6-trieniminium cation in isolated
      conditions. The computed S(2) and S(1) energy profiles do not show any avoided
      crossing feature along the S(1) reaction path and maintain an energy gap >20 kcal
      small middle dotmol(-1). In addition, the analysis of the charge distribution
      shows that there is no qualitative change in the S(2) and S(1) electronic
      structure along the path. Thus, the S(1) state maintains a prevalent ionic (hole
      pair) character whereas the S(2) state maintains a covalent (dot-dot) character.
      These results, together with the analysis of the S(1) reaction coordinate,
      support a two-state, two-mode model of the photoisomerization that constitutes a
      substantial revision of the previously proposed models.

PMID- 10944212
TI  - A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for
      homotypic vacuole fusion.
AB  - Yeast vacuoles undergo priming, docking, and homotypic fusion, although little
      has been known of the connections between these reactions. Vacuole-associated
      Vam2p and Vam6p (Vam2/6p) are components of a 65S complex containing SNARE
      proteins. Upon priming by Sec18p/NSF and ATP, Vam2/6p is released as a 38S
      subcomplex that binds Ypt7p to initiate docking. We now report that the 38S
      complex consists of both Vam2/6p and the class C Vps proteins [Reider, S. E. and
      Emr, S. D. (1997) Mol. Biol. Cell 8, 2307-2327]. This complex includes Vps33p, a
      member of the Sec1 family of proteins that bind t-SNAREs. We term this 38S
      complex HOPS, for homotypic fusion and vacuole protein sorting. This unexpected
      finding explains how Vam2/6p associates with SNAREs and provides a mechanistic
      link of the class C Vps proteins to Ypt/Rab action. HOPS initially associates
      with vacuole SNAREs in "cis" and, after release by priming, hops to Ypt7p,
      activating this Ypt/Rab switch to initiate docking.

PMID- 10944213
TI  - The crystal structure of D-lactate dehydrogenase, a peripheral membrane
      respiratory enzyme.
AB  - d-Lactate dehydrogenase (d-LDH) of Escherichia coli is a peripheral membrane
      respiratory enzyme involved in electron transfer, located on the cytoplasmic side
      of the inner membrane. d-LDH catalyzes the oxidation of d-lactate to pyruvate,
      which is coupled to transmembrane transport of amino acids and sugars. Here we
      describe the crystal structure at 1.9 A resolution of the three domains of d-LDH:
      the flavin adenine dinucleotide (FAD)-binding domain, the cap domain, and the
      membrane-binding domain. The FAD-binding domain contains the site of d-lactate
      reduction by a noncovalently bound FAD cofactor and has an overall fold similar
      to other members of a recently discovered FAD-containing family of proteins. This
      structural similarity extends to the cap domain as well. The most prominent
      difference between d-LDH and the other members of the FAD-containing family is
      the membrane-binding domain, which is either absent in some of these proteins or
      differs significantly. The d-LDH membrane-binding domain presents an
      electropositive surface with six Arg and five Lys residues, which presumably
      interacts with the negatively charged phospholipid head groups of the membrane.
      Thus, d-LDH appears to bind the membrane through electrostatic rather than
      hydrophobic forces.

PMID- 10944214
TI  - Analysis of topoisomerase function in bacterial replication fork movement: use of
      DNA microarrays.
AB  - We used DNA microarrays of the Escherichia coli genome to trace the progression
      of chromosomal replication forks in synchronized cells. We found that both DNA
      gyrase and topoisomerase IV (topo IV) promote replication fork progression. When
      both enzymes were inhibited, the replication fork stopped rapidly. The elongation
      rate with topo IV alone was 1/3 of normal. Genetic data confirmed and extended
      these results. Inactivation of gyrase alone caused a slow stop of replication.
      Topo IV activity was sufficient to prevent accumulation of (+) supercoils in
      plasmid DNA in vivo, suggesting that topo IV can promote replication by removing
      (+) supercoils in front of the chromosomal fork.

PMID- 10944215
TI  - Intramolecular control of transcriptional activity by the NK2-specific domain in
      NK-2 homeodomain proteins.
AB  - The developmentally important homeodomain transcription factors of the NK-2 class
      contain a highly conserved region, the NK2-specific domain (NK2-SD). The function
      of this domain, however, remains unknown. The primary structure of the NK2-SD
      suggests that it might function as an accessory DNA-binding domain or as a
      protein-protein interaction interface. To assess the possibility that the NK2-SD
      may contribute to DNA-binding specificity, we used a PCR-based approach to
      identify a consensus DNA-binding sequences for Nkx2.2, an NK-2 family member
      involved in pancreas and central nervous system development. The consensus
      sequence (T(C)(T)AAGT(G)(A)(G)(C)TT) is similar to the known binding sequences
      for other NK-2 homeodomain proteins, but we show that the NK2-SD does not
      contribute significantly to specific DNA binding to this sequence. To determine
      whether the NK2-SD contributes to transactivation, we used GAL4-Nkx2. 2 fusion
      constructs to map a powerful transcriptional activation domain in the C-terminal
      region beyond the conserved NK2-SD. Interestingly, this C-terminal region
      functions as a transcriptional activator only in the absence of an intact NK2-SD.
      The NK2-SD also can mask transactivation from the paired homeodomain
      transcription factor Pax6, but it has no effect on transcription by itself. These
      results demonstrate that the NK2-SD functions as an intramolecular regulator of
      the C-terminal activation domain in Nkx2.2 and support a model in which
      interactions through the NK2-SD regulate the ability of NK-2-class proteins to
      activate specific genes during development.

PMID- 10944216
TI  - Cell sorting is analogous to phase ordering in fluids.
AB  - Morphogenetic processes, like sorting or spreading of tissues, characterize early
      embryonic development. An analogy between viscoelastic fluids and certain
      properties of embryonic tissues helps interpret these phenomena. The values of
      tissue-specific surface tensions are consistent with the equilibrium
      configurations that the Differential Adhesion Hypothesis predicts such tissues
      reach after sorting and spreading. Here we extend the fluid analogy to cellular
      kinetics. The same formalism applies to recent experiments on the kinetics of
      phase ordering in two-phase fluids. Our results provide biologically relevant
      information on the strength of binding between cell adhesion molecules under near
      physiological conditions.

PMID- 10944218
TI  - Kinetochore reproduction in animal evolution: cell biological explanation of
      karyotypic fission theory.
AB  - Karyotypic fission theory of Todd offers an explanation for the diverse range of
      diploid numbers of many mammalian taxa. Theoretically, a full complement of
      acrocentric chromosomes can be introduced into a population by chromosomal
      fission. Subsequent inheritance of ancestral chromosomes and paired fission
      derivatives potentially generates a diploid range from the ancestral condition to
      double its number of chromosomes. Although it is undisputed that both chromosomal
      fission and fusion ("Robertsonian rearrangements") have significantly contributed
      to karyological diversity, it is generally assumed that independent events, the
      fission of single chromosomes or the fusion of two chromosomes, are the sources
      of such change. The karyotypic fission idea by contrast posits that all
      mediocentric chromosomes simultaneously fission. Here I propose a specific cell
      biological mechanism for Todd's karyotypic fission concept, "kinetochore
      reproduction theory," where a complete set of dicentric chromatids is synthesized
      during gametogenesis, and kinetochore protein dephosphorylation regulates
      dicentric chromatid segregation. Three postulates of kinetochore reproduction
      theory are: (i) breakage of dicentric chromosomes between centromere pairs forms
      acrocentric derivatives, (ii) de novo capping of newly synthesized acrocentric
      ends with telomeric DNA stabilizes these derivatives, and (iii) mitotic
      checkpoints regulate chromosomal disjunction to generate fissioned karyotypes.
      Subsequent chromosomal rearrangement, especially pericentric inversion, increases
      the probability of genetic isolation amongst incipient sympatric species
      polytypic for fission-generated acrocentric autosomes. This mechanism obviates
      the requirement for numerous independent Robertsonian rearrangements and neatly
      accounts for mammalian karyotype evolution as exemplified in analyses of
      Carnivora, Artiodactyla, and Primates.

PMID- 10944217
TI  - Myosin-V stepping kinetics: a molecular model for processivity.
AB  - Myosin-V is a molecular motor that moves processively along its actin track. We
      have used a feedback-enhanced optical trap to examine the stepping kinetics of
      this movement. By analyzing the distribution of time periods separating discrete
      approximately 36-nm mechanical steps, we characterize the number and duration of
      rate-limiting biochemical transitions preceding each such step. These data show
      that myosin-V is a tightly coupled motor whose cycle time is limited by ADP
      release. On the basis of these results, we propose a model for myosin-V
      processivity.

PMID- 10944219
TI  - Gene inactivation by multiphoton-targeted photochemistry.
AB  - Multiphoton-targeted photochemistry was used to selectively inactivate the
      expression of genes in vertebrate cells. A membrane permeable DNA-associating
      vital dye, ethidium bromide monoacetate (visible wavelength single photon
      absorption peak at 530 nm) was used to photosensitize chromosomes in dividing
      cells. A 100-ps infrared laser beam operating at 1.06 microns was focused onto a
      selected region of a mitotic chromosome corresponding to the sites of the
      nucleolar (ribosomal) genes. Individual cells followed through mitosis
      demonstrated a reduction in the number of nucleoli formed in daughter cells that
      corresponded to the number of nucleolar genes sites irradiated. These results
      demonstrate the ability to selectively manipulate genes by using the focal point
      specificity characteristic of multiphoton microscopy. This technique should have
      wide biotechnology applications both in vitro and in vivo.

PMID- 10944220
TI  - Serotonin 2B receptor is required for heart development.
AB  - Several lines of evidence suggest that the serotonin (5-hydroxytryptamine, 5-HT)
      regulates cardiovascular functions during embryogenesis and adulthood. 5-HT binds
      to numerous cognate receptors to initiate its biological effects. However, none
      of the 5-HT receptor disruptions in mice have yet resulted in embryonic defects.
      Here we show that 5-HT(2B) receptor is an important regulator of cardiac
      development. We found that inactivation of 5-HT(2B) gene leads to embryonic and
      neonatal death caused by heart defects. 5-HT(2B) mutant embryos exhibit a lack of
      trabeculae in the heart and a specific reduction in the expression levels of a
      tyrosine kinase receptor, ErbB-2, leading to midgestation lethality. These in
      vivo data suggest that the Gq-coupled receptor 5-HT(2B) uses the signaling
      pathway of tyrosine kinase receptor ErbB-2 for cardiac differentiation. All
      surviving newborn mice display a severe ventricular hypoplasia caused by impaired
      proliferative capacity of myocytes. In adult mutant mice, cardiac
      histopathological changes including myocyte disarray and ventricular dilation
      were consistently observed. Our results constitute genetic evidence that 5-HT via
      5-HT(2B) receptor regulates differentiation and proliferation of developing and
      adult heart. This mutation provides a genetic model for cardiopathy and should
      facilitate studies of both the pathogenesis and therapy of cardiac disorders in
      humans.

PMID- 10944221
TI  - The basic helix-loop-helix transcription factor capsulin controls spleen
      organogenesis.
AB  - Formation of numerous internal organs involves reciprocal epithelial-mesenchymal
      signaling and subsequent patterning and growth of the organ primordium. Capsulin
      is a basic helix-loop-helix transcription factor expressed in mesenchymal cells
      that encapsulate the epithelial primordia of internal organs, including the
      kidney and lung, as well as the epicardium, which gives rise to the coronary
      arteries. Capsulin is also expressed in the mesothelium that gives rise to the
      spleen. We demonstrate that mice homozygous for a capsulin null mutation fail to
      form a spleen. The homeobox genes Hox11 and Bapx1, shown previously to be
      essential regulators of spleen organogenesis, and a lacZ reporter introduced into
      the capsulin locus, were expressed in the early splenic primordium, derived from
      the splanchnic mesoderm, of homozygous mutant embryos. However, this primordium
      failed to develop beyond an initial group of precursor cells and underwent rapid
      apoptosis. The phenotype of capsulin mutant mice demonstrates that capsulin acts
      within a subpopulation of splanchnic mesodermal cells to control an essential
      early step in spleen organogenesis that is likely to represent a point of
      regulatory convergence of the capsulin, Hox11, and Bapx1 genes.

PMID- 10944222
TI  - Restriction of ectopic recombination by interhomolog interactions during
      Saccharomyces cerevisiae meiosis.
AB  - In Saccharomyces cerevisiae meiosis, recombination occurs frequently between
      sequences at the same location on homologs (allelic recombination) and can take
      place between dispersed homologous sequences (ectopic recombination). Ectopic
      recombination occurs less often than does allelic, especially when homologous
      sequences are on heterologous chromosomes. To account for this, it has been
      suggested that homolog pairing (homolog colocalization and alignment) either
      promotes allelic recombination or restricts ectopic recombination. The latter
      suggestion was tested by examining ectopic recombination in two cases where
      normal interhomolog relationships are disrupted. In the first case, one member of
      a homolog pair was replaced by a homologous (related but not identical)
      chromosome that has diverged sufficiently to prevent allelic recombination. In
      the second case, ndj1 mutants were used to delay homolog pairing and synapsis.
      Both circumstances resulted in a substantial increase in the frequency of ectopic
      recombination between arg4-containing plasmid inserts located on heterologous
      chromosomes. These findings suggest that, during normal yeast meiosis,
      progressive homolog colocalization, alignment, synapsis, and allelic
      recombination restrict the ability of ectopically located sequences to find each
      other and recombine. In the absence of such restrictions, the meiotic homology
      search may encompass the entire genome.

PMID- 10944223
TI  - Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type
      2 by enhanced inactivation and reduced current.
AB  - The pathomechanism of familial hypokalemic periodic paralysis (HypoPP) is a
      mystery, despite knowledge of the underlying dominant point mutations in the
      dihydropyridine receptor (DHPR) voltage sensor. In five HypoPP families without
      DHPR gene defects, we identified two mutations, Arg-672-->His and -->Gly, in the
      voltage sensor of domain 2 of a different protein: the skeletal muscle sodium
      channel alpha subunit, known to be responsible for hereditary muscle diseases
      associated with myotonia. Excised skeletal muscle fibers from a patient
      heterozygous for Arg-672-->Gly displayed depolarization and weakness in low
      potassium extracellular solution. Slowing and smaller size of action potentials
      were suggestive of excitability of the wild-type channel population only.
      Heterologous expression of the two sodium channel mutations revealed a 10-mV left
      shift of the steady-state fast inactivation curve enhancing inactivation and a
      sodium current density that was reduced even at potentials at which inactivation
      was removed. Decreased current and small action potentials suggested a low
      channel protein density. The alterations are decisive for the pathogenesis of
      episodic muscle weakness by reducing the number of excitable sodium channels
      particularly at sustained membrane depolarization. The results prove that SCN4A,
      the gene encoding the sodium channel alpha subunit of skeletal muscle is
      responsible for HypoPP-2 which does not differ clinically from DHPR-HypoPP.
      HypoPP-2 represents a disease caused by enhanced channel inactivation and current
      reduction showing no myotonia.

PMID- 10944224
TI  - Multiple functional defects in peripheral autonomic organs in mice lacking
      muscarinic acetylcholine receptor gene for the M3 subtype.
AB  - Muscarinic acetylcholine receptors consist of five distinct subtypes and have
      been important targets for drug development. In the periphery, muscarinic
      acetylcholine receptors mediate cholinergic signals to autonomic organs, but
      specific physiological functions of each subtype remain poorly elucidated. Here,
      we have constructed and analyzed mutant mice lacking the M(3) receptor and have
      demonstrated that this subtype plays key roles in salivary secretion, pupillary
      constriction, and bladder detrusor contractions. However, M(3)-mediated signals
      in digestive and reproductive organs are dispensable, likely because of redundant
      mechanisms through other muscarinic acetylcholine receptor subtypes or other
      mediators. In addition, we have found prominent urinary retention only in the
      male, which indicates a considerable sex difference in the micturition mechanism.
      Accordingly, this mutant mouse should provide a useful animal model for
      investigation of human diseases that are affected in the peripheral cholinergic
      functions.

PMID- 10944225
TI  - Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of
      thalassemic patients.
AB  - Mononuclear cells from peripheral blood of thalassemic patients were treated with
      morpholino oligonucleotides antisense to aberrant splice sites in mutant beta
      globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct
      splicing and translation of beta-globin mRNA, increasing the hemoglobin (Hb) A
      synthesis in erythroid cells from patients with IVS2-654/beta(E), IVS2-745/IVS2
      745, and IVS2-745/IVS2-1 genotypes. The maximal Hb A level for repaired IVS2-745
      mutation was approximately 30% of normal; Hb A was still detectable 9 days after
      a single treatment with oligonucleotide. Thus, expression of defective beta
      globin genes was repaired and significant level of Hb A was restored in a cell
      population that would be targeted in clinical applications of this approach.

PMID- 10944226
TI  - Somatic deletions in hereditary breast cancers implicate 13q21 as a putative
      novel breast cancer susceptibility locus.
AB  - A significant proportion of familial breast cancers cannot be explained by
      mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify
      predisposition loci for breast cancer by using mathematical models to identify
      early somatic genetic deletions in tumor tissues followed by targeted linkage
      analysis. Comparative genomic hybridization was used to study 61 breast tumors
      from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations.
      Branching and phylogenetic tree models predicted that loss of 13q was one of the
      earliest genetic events in hereditary cancers. In a Swedish family with five
      breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the
      minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared
      13q21 germ-line haplotype in the family. Targeted linkage analysis was carried
      out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no
      detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of
      odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10).
      The multipoint logarithm of odds score under heterogeneity was 3.46. The results
      were further evaluated by simulation to assess the probability of obtaining
      significant evidence in favor of linkage by chance as well as to take into
      account the possible influence of the BRCA2 locus, located at a recombination
      fraction of 0.25 from the new locus. The simulation substantiated the evidence of
      linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative
      breast cancer predisposition locus in other populations.

PMID- 10944227
TI  - Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis.
AB  - Smad4/DPC4 (deleted in pancreatic carcinoma, locus 4) is a tumor suppressor gene
      lost at high frequency in cancers of the pancreas and other gastrointestinal
      organs. Smad4 encodes a key intracellular messenger in the transforming growth
      factor beta (TGF-beta) signaling cascade. TGF-beta is a potent inhibitor of the
      growth of epithelial cells; thus, it has been assumed that loss of Smad4 during
      tumor progression relieves this inhibition. Herein, we show that restoration of
      Smad4 to human pancreatic carcinoma cells suppressed tumor formation in vivo, yet
      it did not restore sensitivity to TGF-beta. Rather, Smad4 restoration influenced
      angiogenesis, decreasing expression of vascular endothelial growth factor and
      increasing expression of thrombospondin-1. In contrast to the parental cell line
      and to control transfectants that produced rapidly growing tumors in vivo, Smad4
      revertants induced small nonprogressive tumors with reduced vascular density.
      These data define the control of an angiogenic switch as an alternative,
      previously unknown mechanism of tumor suppression for Smad4 and identify the
      angiogenic mediators vascular endothelial growth factor and thrombospondin-1 as
      key target genes.

PMID- 10944228
TI  - Mosaicism in the alpha-like protein genes of group B streptococci.
AB  - Members of a family of repeat-containing surface proteins of group B streptococci
      (GBS) defined by the alpha C and Rib proteins exhibit size variability and cross
      reactivity and have been studied as potential vaccine components. We report
      evidence of horizontal DNA transfer with subsequent recombination as a mechanism
      generating diversity within this antigen family. Alp2 and Alp3 are additional
      members of the alpha C protein family identified in strains of the emerging GBS
      serotypes V and VIII. Each contains an overall genetic organization highly
      similar to that of the alpha C and Rib proteins, including a tandem repeat region
      and conserved N- and C-terminal regions. Among different strains, protein size
      varies according to the number of tandem repeats within the corresponding gene.
      Unlike the alpha C and Rib proteins, however, the newly described alpha-like
      proteins contain other regions, including one similar to the IgA-binding region
      of the GBS beta C protein, a nontandem repeat region, and an isolated repeat
      highly homologous to the alpha C repeat. Sequence analysis of the regions
      flanking the alpha C protein gene on a 13.7-kb insert reveals several ORFs that
      are likely to be involved in basic metabolic pathways. Analysis of corresponding
      flanking regions in other GBS strains, including the parent strains of the newly
      described alpha-like proteins, shows striking conservation among all strains
      studied. These findings indicate that the alpha-like proteins are encoded by
      mosaic variants at a single genomic locus and suggest that recombination after
      horizontal DNA transfer is a means of generating diversity within this protein
      family.

PMID- 10944229
TI  - Identification of type II restriction and modification systems in Helicobacter
      pylori reveals their substantial diversity among strains.
AB  - A total of 22 type II restriction endonucleases with 18 distinct specificities
      have been identified in six Helicobacter pylori strains. Among these 18
      specificities are three completely new endonucleases, Hpy178III, Hpy99I, and
      Hpy188I, that specifically cleave DNA at TCNNGA, CGWCG, and TCNGA sites,
      respectively. The set of endonucleases identified in each strain varies, but all
      have four- or five-base recognition sequences. Among 16 H. pylori strains,
      examination of the DNA modification status at the recognition sites of 15
      restriction endonucleases reveals that each strain has a substantially different
      complement of type II modification systems. We conclude that the type II
      restriction-modification systems in H. pylori are highly diverse between strains,
      a unique characteristic of H. pylori. The diverse methylation status of H. pylori
      chromosomal DNA may serve as a new typing system to discriminate H. pylori
      isolates for epidemiological and clinical purposes. This study also demonstrates
      that H. pylori is a rich source of type II restriction endonucleases.

PMID- 10944230
TI  - Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium
      tuberculosis.
AB  - Ethionamide (ETA) is an important component of second-line therapy for the
      treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and
      an examination of drug metabolites formed by whole cells of Mycobacterium
      tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S
      oxidation before interacting with its cellular target. ETA is metabolized by MTb
      to a 4-pyridylmethanol product remarkably similar in structure to that formed by
      the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated
      that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb,
      confers ETA resistance whereas overproduction of an adjacent, clustered
      monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA
      appears to be negatively regulated by EtaR and correlates directly with
      [(14)C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible
      for thioamide oxidation and subsequent toxicity. Coding sequence mutations in
      EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape
      Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl
      containing drugs including ETA, thiacetazone, and thiocarlide.

PMID- 10944231
TI  - Ca2+-dependent regulation of synaptic SNARE complex assembly via a calmodulin-
      and phospholipid-binding domain of synaptobrevin.
AB  - Synaptic core complex formation is an essential step in exocytosis, and assembly
      into a superhelical structure may drive synaptic vesicle fusion. To ascertain how
      Ca(2+) could regulate this process, we examined calmodulin binding to recombinant
      core complex components. Surface plasmon resonance and pull-down assays revealed
      Ca(2+)-dependent calmodulin binding (K(d) = 500 nM) to glutathione S-transferase
      fusion proteins containing synaptobrevin (VAMP 2) domains but not to syntaxin 1
      or synaptosomal-associated protein of 25 kDa (SNAP-25). Deletion mutations,
      tetanus toxin cleavage, and peptide synthesis localized the calmodulin-binding
      domain to VAMP(77-94), immediately C-terminal to the tetanus toxin cleavage site
      (Q(76)-F(77)). In isolated synaptic vesicles, Ca(2+)/calmodulin protected native
      membrane-inserted VAMP from proteolysis by tetanus toxin. Assembly of a (35)S
      SNAP-25, syntaxin 1 GST-VAMP(1-96) complex was inhibited by Ca(2+)/calmodulin,
      but assembly did not mask subsequent accessibility of the calmodulin-binding
      domain. The same domain contains a predicted phospholipid interaction site. SPR
      revealed calcium-independent interactions between VAMP(77-94) and liposomes
      containing phosphatidylserine, which blocked calmodulin binding. Circular
      dichroism spectroscopy demonstrated that the calmodulin/phospholipid-binding
      peptide displayed a significant increase in alphahelical content in a hydrophobic
      environment. These data provide insight into the mechanisms by which Ca(2+) may
      regulate synaptic core complex assembly and protein interactions with membrane
      bilayers during exocytosis.

PMID- 10944232
TI  - Abeta 1-40-related reduction in functional hyperemia in mouse neocortex during
      somatosensory activation.
AB  - Peptides derived from proteolytic processing of the beta-amyloid precursor
      protein (APP), including the amyloid-beta peptide (Abeta), play a critical role
      in the pathogenesis of Alzheimer's dementia. We report that transgenic mice
      overexpressing APP and Abeta have a profound attenuation in the increase in
      neocortical blood flow elicited by somatosensory activation. The impairment is
      highly correlated with brain Abeta concentration and is reproduced in normal mice
      by topical neocortical application of exogenous Abeta1-40 but not Abeta1-42.
      Overexpression of M146L mutant presenilin-1 in APP mice enhances the production
      of Abeta1-42 severalfold, but it does not produce a commensurate attenuation of
      the hyperemic response. APP and Abeta overexpression do not diminish the
      intensity of neural activation, as reflected by the increase in somatosensory
      cortex glucose usage. Thus, Abeta-induced alterations in functional hyperemia
      produce a potentially deleterious mismatch between substrate delivery and energy
      demands imposed by neural activity.

PMID- 10944233
TI  - An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin
      is a major endothelium-dependent vasodilator in resistance vessels of wild-type
      and endothelial NO synthase knockout mice.
AB  - In addition to nitric oxide (NO) and prostacyclin (PGI(2)), the endothelium
      generates the endothelium-derived hyperpolarizing factor (EDHF). We set out to
      determine whether an EDHF-like response can be detected in wild-type (WT) and
      endothelial NO synthase knockout mice (eNOS -/-) mice. Vasodilator responses to
      endothelium-dependent agonists were determined in vivo and in vitro. In vivo,
      bradykinin induced a pronounced, dose-dependent decrease in mean arterial
      pressure (MAP) which did not differ between WT and eNOS -/- mice and was
      unaffected by treatment with N(omega)-nitro-l-arginine methyl ester and
      diclofenac. In the saline-perfused hindlimb of WT and eNOS -/- mice, marked
      N(omega)-nitro-l-arginine (l-NA, 300 micromol/liter)- and diclofenac-insensitive
      vasodilations in response to both bradykinin and acetylcholine (ACh) were
      observed, which were more pronounced than the agonist-induced vasodilation in the
      hindlimb of WT in the absence of l-NA. This endothelium-dependent, NO/PGI(2)
      independent vasodilatation was sensitive to KCl (40 mM) and to the combination of
      apamin and charybdotoxin. Gap junction inhibitors (18alpha-glycyrrhetinic acid,
      octanol, heptanol) and CB-1 cannabinoid-receptor agonists (Delta(9)
      tetrahydrocannabinol, HU210) impaired EDHF-mediated vasodilation, whereas
      inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine
      receptors had no effect on EDHF-mediated responses. These results demonstrate
      that in murine resistance vessels the predominant agonist-induced endothelium
      dependent vasodilation in vivo and in vitro is not mediated by NO, PGI(2), or a
      cytochrome P450 metabolite, but by an EDHF-like principle that requires
      functional gap junctions.

PMID- 10944234
TI  - Inactivation of catecholamines by superoxide gives new insights on the
      pathogenesis of septic shock.
AB  - A major feature of septic shock is the development of a vascular crisis
      characterized by nonresponsiveness to sympathetic vasoconstrictor agents and the
      subsequent irreversible fall in blood pressure. In addition, sepsis, like other
      inflammatory conditions, results in a large increase in the production of free
      radicals, including superoxide anions (O(2)) within the body. Here we show that
      O(2) reacts with catecholamines deactivating them in vitro. Moreover, this
      deactivation would appear to account for the hyporeactivity to exogenous
      catecholamines observed in sepsis, because administration of a superoxide
      dismutase (SOD) mimetic to a rat model of septic shock to remove excess O(2)
      restored the vasopressor responses to norepinephrine. This treatment with the SOD
      mimetic also reversed the hypotension in these animals; suggesting that
      deactivation of endogenous norepinephrine by O(2) contributes significantly to
      this aspect of the vascular crisis. Indeed, the plasma concentrations of both
      norepinephrine and epinephrine in septic rats treated with the SOD mimetic were
      significantly higher than in untreated rats. Interestingly, the plasma
      concentrations for norepinephrine and epinephrine were inversely related to the
      plasma concentrations of adrenochromes, the product of the autoxidation of
      catecholamines initiated by O(2). We propose, therefore, that the use of a SOD
      mimetic represents a new paradigm for the treatment of septic shock. By removing
      O(2), exogenous and endogenous catecholamines are protected from autoxidation. As
      a result, both hyporeactivity and hypotension are reversed, generation of
      potentially toxic adrenochromes is reduced, and survival rate is improved.

PMID- 10944235
TI  - Coordinated regulation of fetal and maternal prostaglandins directs successful
      birth and postnatal adaptation in the mouse.
AB  - Cyclooxygenase (COX)-derived prostaglandins (PGs) regulate numerous maternal
      fetal interactions during pregnancy. PGs stimulate uterine contractions and
      prepare the cervix for parturition, whereas in the fetus, PGs maintain patency of
      the ductus arteriosus (DA), a vascular shunt that transmits oxygenated placental
      blood to the fetal systemic circulation. However, the origin and site of action
      of these PGs remain undefined. To address this, we analyzed mice lacking COX-1
      (null mutation) or COX-2 (pharmacologic inhibition) or pups with a double null
      mutation. Our results show that COX-1 in the uterine epithelium is the major
      source of PGs during labor and that COX-1(-/-) females experience parturition
      failure that is reversible by exogenous PGs. Using embryo transfer experiments,
      we also show that successful delivery occurs in COX-1(-/-) recipient mothers
      carrying wild-type pups, establishing the sufficiency of fetal PGs for
      parturition. Although patency of the DA is PG dependent, neither COX-1 nor COX-2
      expression was detected in the fetal or postnatal DA, and offspring with a double
      null mutation died shortly after birth with open DAs. These results suggest that
      DA patency depends on circulating PGs acting on specific PG receptors within the
      DA. Collectively, these findings demonstrate the coordinated regulation of fetal
      and maternal PGs at the time of birth but raise concern regarding the use of
      selective COX inhibitors for the management of preterm labor.

PMID- 10944236
TI  - Activation and inhibition of G protein-coupled inwardly rectifying potassium
      (Kir3) channels by G protein beta gamma subunits.
AB  - G protein-coupled inwardly rectifying potassium (GIRK) channels can be activated
      or inhibited by different classes of receptors, suggesting a role for G proteins
      in determining signaling specificity. Because G protein betagamma subunits
      containing either beta1 or beta2 with multiple Ggamma subunits activate GIRK
      channels, we hypothesized that specificity might be imparted by beta3, beta4, or
      beta5 subunits. We used a transfection assay in cell lines expressing GIRK
      channels to examine effects of dimers containing these Gbeta subunits. Inwardly
      rectifying K(+) currents were increased in cells expressing beta3 or beta4, with
      either gamma2 or gamma11. Purified, recombinant beta3gamma2 and beta4gamma2 bound
      directly to glutathione-S-transferase fusion proteins containing N- or C-terminal
      cytoplasmic domains of GIRK1 and GIRK4, indicating that beta3 and beta4, like
      beta1, form dimers that bind to and activate GIRK channels. By contrast, beta5
      containing dimers inhibited GIRK channel currents. This inhibitory effect was
      obtained with either beta5gamma2 or beta5gamma11, was observed with either
      GIRK1,4 or GIRK1,2 channels, and was evident in the context of either basal or
      agonist-induced currents, both of which were mediated by endogenous Gbetagamma
      subunits. In cotransfection assays, beta5gamma2 suppressed beta1gamma2-activated
      GIRK currents in a dose-dependent manner consistent with competitive inhibition.
      Moreover, we found that beta5gamma2 could bind to the same GIRK channel
      cytoplasmic domains as other, activating Gbetagamma subunits. Thus, beta5
      containing dimers inhibit Gbetagamma-stimulated GIRK channels, perhaps by
      directly binding to the channels. This suggests that beta5-containing dimers
      could act as competitive antagonists of other Gbetagamma dimers on GIRK channels.

PMID- 10944237
TI  - Visuo-tactile cross-modal associations in cortical somatosensory cells.
AB  - Recent studies show that cells in the somatosensory cortex are involved in the
      short-term retention of tactile information. In addition, some somatosensory
      cells appear to retain visual information that has been associated with the touch
      of an object. The presence of such cells suggests that nontactile stimuli
      associated with touch have access to cortical neuron networks engaged in the
      haptic sense. Thus, we inferred that somatosensory cells would respond to
      behaviorally associated visual and tactile stimuli. To test this assumption,
      single units were recorded from the anterior parietal cortex (Brodmann's areas
      3a, 3b, 1, and 2) of monkeys performing a visuo-haptic delay task, which required
      the memorization of a visual cue for a tactile choice. Most cells responding to
      that cue responded also to the corresponding object presented for tactile choice.
      Significant correlations were observed in some cells between their differential
      reactions to tactile objects and their differential reactions to the associated
      visual cues. Some cells were recorded in both the cross-modal task and a haptic
      unimodal task, where the animal had to retain a tactile cue for a tactile choice.
      In most of these cells, correlations were observed between stimulus-related
      firing in corresponding cue periods of the two tasks. These findings suggest that
      cells in somatosensory cortex are the components of neuronal networks
      representing tactile information. Associated visual stimuli may activate such
      networks through visuo-haptic associations established by behavioral training.

PMID- 10944243
TI  - How precise are measurements of unit-cell dimensions from single crystals?
AB  - The results of single-site and many-site measurements of cell dimensions from
      single crystals are compared for Bond and four-circle diffractometers using
      samples of corundum (essentially pure rhombohedral alpha-Al2O3, aluminum oxide)
      of high diffraction quality, where the effects of small changes in temperature
      and composition (Cr2O3, chromium oxide, in solid solution) can be taken into
      account. Similar comparisons are made for four-circle diffractometer measurements
      on ruby (alpha-Al2O3, with 0.46 wt % Cr in solid solution). The precisions are
      some parts in 10(5). There is partial support for the Taylor-Kennard [Acta Cryst.
      (1986), B42, 112-120] dictum that standard uncertainties (s.u.s) of cell
      parameters from routine four-circle diffractometer measurements are less than
      those for many-site measurements by factors of 5 for cell lengths and 2.5 for
      cell angles. For organic crystals, independent repetitions of adequate quality
      for comparison and analysis of routine four-circle diffractometer measurements
      are available only for alpha-oxalic acid dihydrate and anthracene. The
      experimental standard uncertainties given for these two crystals agree reasonably
      well with the sample s.u.s at room temperature, but appreciably less well at
      approximately 100 K, again giving partial support to the Taylor-Kennard dictum.
      The relation between specimen characteristics and attainable precision is
      emphasized; the precisions for routine measurements on good quality organic
      crystals are some parts in 10(4). Area-detector measurements of cell dimensions
      have also been appraised; currently published s.u.s from such measurements appear
      to be highly unreliable, and this is supported by a recent analysis of the
      operation of such diffractometers [Paciorek et al. (1999). Acta Cryst. A55, 543
      557]. Formulation of a standard protocol for such measurements is badly needed.
      The dangers inherent in high degrees of replication are illustrated by recounting
      Kapteyn's Parable of the Chinese Emperor. Attention is drawn to the fact that
      there has been little improvement in claimed precisions over the past 40-60
      years.

PMID- 10944241
TI  - Quitting cigarette smoking results in a fast improvement of in vivo oxidation
      injury (determined via plasma, serum and urinary isoprostane).
AB  - Isoprostanes (IP) have been identified as reliable markers of in vivo oxidation
      injury. Recently, in vascular tissue and blood as well as urine of cigarette
      smokers, increased IP values have been discovered. We examined 47 adults (26
      males, 21 females; aged 30-66 years), admitted to a cardiovascular unit on an
      outpatient basis, with various risk factors but without any sign of manifestation
      of atherosclerosis. Refraining from cigarette smoking for a few days resulted in
      a significant drop of plasma, serum, and urinary 8-epi-PGF(2alpha). Thereafter, a
      further continuous decrease was monitored, reaching a steady state after about 4
      weeks after quitting cigarette smoking. Prevalues of 8-epi-PGF(2alpha) were
      higher, depending on the type and number of risk factors; the decrease after
      quitting, however, was comparable. These results indicate that exsmokers may
      rapidly recover from their enhanced in vivo oxidation.

PMID- 10944244
TI  - Towards a unified description of the AMOB2O5 (A=K, Rb, Cs, Tl; M=Nb, Ta) family
      of compounds.
AB  - Single-crystal X-ray diffraction data (Mo Kalpha radiation) are used to re-refine
      the structure of RbNbOB2O5, rubidium niobium oxo pyroborate. The structure is
      refined as an incommensurate modulated structure with superspace group symmetry
      Pmn2(1)(0,0.4,0)s and lattice parameters a = 7.406 (2), b = 3.939 (2) and c =
      9.475 (2) A. Refinement on 3242 unique reflections converged to R = 0.031, while
      a previous conventional superstructure refinement led to R = 0.090. This lowering
      of the R factor goes hand-in-hand with a substantial reduction in the number of
      refined parameters. The refinement strongly suggests that the structure is
      effectively incommensurately modulated, despite an apparently rational magnitude
      of the primary modulation wave-vector and overlap of satellite reflections.

PMID- 10944245
TI  - Bond-valence parameters for ammonium-anion interactions.
AB  - Bond-valence parameters r0 and b, relating bond valence and bond length, are
      calculated for interactions between the ammonium ion and anions X = O, F, Cl.
      Searches in the Cambridge Structural Database (CSD) and in the Inorganic Crystal
      Structural Database (ICSD) were performed to obtain the lengths of NH4+...X
      contacts for ammonium ion environments in different structures. The procedure,
      which represents an extension of previous methods, allows certain environments to
      be rejected and enables the calculation of r0 and b from a reasonable range of
      interaction distances. Results are in very good agreement with the expected
      values on the basis of the assumed bond-valence model and their overall
      applicability to ammonium ion interactions is discussed.

PMID- 10944246
TI  - Neutron Rietveld refinement of the incommensurate phase of the ordered perovskite
      Pb2CoWO6.
AB  - The incommensurate structure of lead cobalt tungstate has been refined by the
      Rietveld method on neutron data collected at 250 K. The space group is planar
      monoclinic 12/m(alpha0gamma)0s [a = 7.9602 (4), b = 5.6779 (3), c = 5.6967 (3) A,
      beta = 90.047 (5)degrees, q(inc) = 0.9000 (9)a* + 0.1735 (6)c*]. The use of
      powder diffraction techniques to investigate ferroelastic modulated phases is
      discussed and compared with a previous polydomain single-crystal structural
      analysis. The modulated displacements of light atoms have been determined,
      allowing an accurate description of the modulation of both the cations and the O
      atom framework. The refinement suggests a displacive model for the phase
      transition, involving significant atomic shifts for Pb atoms and a quite complex
      mixing of tilt and deformation of the oxygen octahedra. The average character of
      this modulated structure is antiferroelectric.

PMID- 10944247
TI  - Structure of uranium(VI) oxide dihydrate, UO3.2H2O; synthetic meta-schoepite
      (UO2)4O(OH)6.5H2O.
AB  - Structure of uranium(VI) oxide dihydrate, P03.2H20; synthetic meta-schoepite
      (UO2)40(OH)6.5H20 f The structure of uranium oxide dihydrate, also known as meta
      schoepite (UO2)4O(OH)6.5H2O, has been determined from a synthetic single crystal.
      The structure, at 150 K, space group Pbcn, lattice constants a = 14.6861 (4), b =
      13.9799 (3) and c = 16.7063 (5) A, consists of layers of stoichiometry
      (UO2)4O(OH)6, formed from edge-sharing UO7 pentagonal bipyramids, interleaved
      with hydrogen-bonded water molecules. Three of the layer hydroxyl groups are
      linked through hydrogen bonding to single water molecules and the three remaining
      OH units form interactions with water molecules that each act as acceptors in two
      hydrogen bonds. One of the water molecules in the inter-layer region is
      disordered over two symmetry-related sites and forms hydrogen-bonded interactions
      only within the layer and with the uranyl O atoms. The relationship of the
      structure of meta-schoepite to that of schoepite is discussed in detail.

PMID- 10944248
TI  - Study of NH4+ in the zeolite phillipsite by combined synchrotron powder
      diffraction and IR spectroscopy.
AB  - The Rietveld refinement on synchrotron data of three natural hydrated NH4+
      exchanged phillipsites with different Si/Al ratios allowed acceptable assignment
      of the NH4+ sites. These phillipsites display the typical monoclinic P2(1)/m
      cell, whose volume increases with increasing numbers of NH4+ ions, which are
      refined in the two sites labelled I and II. Some residual Na+ is retained in the
      site labelled II'. Distortion of the Si/Al tetrahedra, which affects some
      absorption bands in the IR spectra, seems to be mainly due to the distribution of
      Al in the framework, while the interaction of NH4+ with the O atoms of the
      framework seems to play a minor role. NH4+ in both sites acts as a donor in
      hydrogen bonding with O atoms of the framework and water molecules. NH4+ in site
      I has three H atoms interacting with O atoms of the framework and a number of
      interactions with water O atoms. In all three samples, monocentric and dicentric
      connections are formed. NH4+ in site II has one H atom interacting with O atoms
      of the framework and a number of interactions with water O atoms. Two monocentric
      connections and a quadricentric one were found in sample (1), three dicentric
      connections and a monocentric one in sample (2), and three monocentric
      connections and a dicentric one in sample (3).

PMID- 10944249
TI  - Electron density and atomic displacements in KTaO3.
AB  - The atomic interactions and anharmonicity of atomic displacements in the virtual
      ferroelectric KTaO3, potassium tantalate, have been studied using accurate single
      crystal X-ray diffraction at room temperature. The multipole analysis of electron
      density and Gram-Charlier series description of anharmonic atomic displacements
      allowed us to perform a quantitative analysis of the chemical bonding and atomic
      motion in this crystal. Closed-shell interactions between Ta-O and K-O pairs of
      atoms were found, while no interaction was observed for the Ta-K and O-O atomic
      pairs. The character of the anharmonic atomic displacements is discussed and
      compared with those in SrTiO3.

PMID- 10944250
TI  - Structural phase transitions of HfV2 at low temperatures.
AB  - We report a high-resolution synchrotron X-ray powder diffraction study on HfV(2),
      hafnium divanadium, at low temperatures. In this work we show, for the first
      time, a complete sequence of structural phase transitions of HfV(2) from cubic
      (Fd3m) to tetragonal (I4(1)/amd) to orthorhombic (Imma) in succession as
      temperature decreases. Peak splitting and extra diffraction peaks owing to
      lattice distortion can be clearly distinguished for the low-symmetry phases. The
      atomic positions and lattice parameters were obtained by Rietveld refinement. The
      bond lengths and angles of the HfV(2) crystal structure at the low-symmetry
      phases were correctly determined from the structure refinement. The face-centered
      cubic (Fd3m) unit cell (Z = 24) transforms to a body-centered tetragonal
      (I4(1)/amd) phase with a 45 degrees rotation relative to the cubic cell and with
      a reduced number of atoms (Z = 12) in the unit cell at a temperature of T = 112
      K. The orthorhombic phase occurs at T = 102 K and it keeps the body-centered
      symmetry (Imma) and Z = 12 in the unit cell. The refinement results indicate that
      there may be a small amount of untransformed cubic phase left over in the lower
      symmetry phases. The abnormal thermal contraction of both tetragonal phase and
      orthorhombic phase marks the significance of structural change in HfV(2).

PMID- 10944251
TI  - Analysis of LiKSO4 crystals in the temperature range from 573 to 943 K.
AB  - The structural phases observed in LiKSO4 crystals due to thermotropic transitions
      have been studied for more than a century. Nowadays many different phases are
      referenced, but some of the results are still controversial. Structural studies
      by single-crystal X-ray diffraction from room temperature to 803 K are presented
      here. Phase II (708 < T < 943 K) is extensively discussed on the basis of ordered
      and disordered models, using harmonic and anharmonic atomic displacements, and
      considering a twinned crystal composed of three orthorhombic domains. Analyses of
      the same phase at different temperatures determine the best structure model.

PMID- 10944253
TI  - A new relation between bond valence and bond distance.
AB  - A new empirical relationship s = s0(R0 - lambda)3/(R - lambda)3 between bond
      distances and bond valences is proposed, where s is the bond valence for the bond
      distance R, s0 is the reference bond valence for the reference system with the
      reference bond distance R0 and lambda is the sum of the cation radii of bonding
      atoms defined by Pauling. Since lambda is the size of the inner electron region,
      R - lambda represents the valence electron region between bonding atoms. The new
      relationship was derived based on the following three hypotheses. (i) The number
      of electrons (p) in the volumes of (R - lambda)3 in a coordination polyhedron are
      equal, even if the bond distances are not equal to each other. (ii) The average
      electron density p/(R - lambda)3 is a measure of covalent bond strength. (iii)
      The sum of the average electron densities around the central atom is conserved,
      even if the coordination number changes. The new relationship is applicable not
      only to polyhedra with one type of ligand atom, but also to polyhedra with two or
      more types of ligand atoms and explains why the Brown-Shannon formula [Brown &
      Shannon (1973). Acta Cryst. A29, 266-282] and the Brown-Altermatt formula [Brown
      & Altermatt (1985). Acta Cryst. B41, 244-247] work well. The new relationship was
      applied to a penta-coordinated silicon compound, strong hydrogen-bond systems and
      some organic compounds with carbon-carbon bonds.

PMID- 10944254
TI  - Identification of two allotwins of mica polytypes in reciprocal space through the
      minimal rhombus unit.
AB  - The X-ray investigation (precession method) of the Ruiz Peak oxybiotite, which is
      well known for the occurrence of a large number of polytypes and twins, revealed
      two complex diffraction patterns, which cannot be identified as long-period
      polytypes. These patterns are analysed in terms of the minimal rhombus, a
      geometrical asymmetric unit in reciprocal space which permits the decomposition
      of the composite reciprocal lattice of a twin or allotwin into the reciprocal
      lattices of the individuals. Both the recorded patterns correspond to a 1M-2M(1)
      allotwin: the relative rotation between the individuals is 120 degrees in one
      case and 60 degrees in the other. The geometrical criteria for evaluating the
      presence of twinning or allotwinning are analysed through these two natural
      examples.

PMID- 10944252
TI  - Ab initio structure determination and Rietveld refinement of a high-temperature
      phase of zirconium hydrogen phosphate and a new polymorph of zirconium
      pyrophosphate from in situ temperature-resolved powder diffraction data.
AB  - The collected in situ temperature-resolved synchrotron powder data revealed that
      the transformation of the recently reported three-dimensional tau-Zr(HPO4)2 to
      cubic ZrP2O7 goes through two intermediate phases. The first intermediate phase,
      rho-Zr(HPO4)2, is formed in a reversible phase transition at 598 K, which
      involves both rearrangement and disordering of the hydrogen phosphate groups of
      tau-Zr(HPO4)2. At 688 K condensation of the hydrogen phosphate groups leads to
      the formation of the second intermediate, a new polymorph of zirconium
      pyrophosphate (beta-ZrP2O7). Heating above 973 K results in the gradual
      transformation of beta-ZrP2O7 to cubic zirconium pyrophosphate (alpha-ZrP2O7).
      The crystal structures of the two intermediate phases were solved from the in
      situ powder diffraction data using direct methods and refined using the Rietveld
      method. Both phases are orthorhombic, space group Pnnm and Z = 2. The lattice
      parameters for the two phases are: p-Zr(HPO4)2: a = 8.1935 (2), b = 7.7090 (2), c
      = 5.4080 (1) A; beta-ZrP2O7: a = 8.3127 (5), b = 6.6389 (4), c = 5.3407 (3) A.
      The formation mechanism for the new zirconium pyrophosphate polymorph, beta
      ZrP2O7, is discussed in relation to structurally restricted soft chemistry.

PMID- 10944255
TI  - Aplanarity of CO3 groups: a theoretical investigation.
AB  - Density functional theory-based calculations have been used to demonstrate that
      the aplanarity of CO3 groups in some carbonates such as dolomite, CaMg(CO3)2,
      aragonite, CaCO3, and norsethite, BaMg(CO3)2, is a ground-state property. This
      distortion stabilizes dolomite by approximately 500 J mol(-1). Up to at least 6
      GPa, the aplanarity of CO3 groups in dolomite is independent of pressure. In
      aragonite the aplanarity increases slightly on increasing pressure, while a
      significant tilting of the CO3 groups occurs. The calculations do not support
      previous findings of anomalously low values for the pressure derivative of the
      bulk moduli, B', of aragonite and dolomite. Instead, the computed pressure
      dependences of the unit-cell volumes correspond to B' = 5.0 (5) for aragonite and
      B' = 4(1) for dolomite, when fitted with a third-order Birch-Murnaghan equation
      of-state.

PMID- 10944256
TI  - A new stacking motif: complex alloy structures interpreted as modulated
      structures.
AB  - The structures of lambda-Al4Mn, manganese aluminide, kappa-Al177Cr49Ni, chromium
      nickel aluminide, and epsilon-Al4Cr, chromium aluminide, which have been
      described in terms of the aggregation of clusters until now, are interpreted as
      modulated structures. They are basically composed of close-packed layers with
      ordered atomic vacancies. The observed stacking motif of the atoms can be found
      in many phases related to icosahedral and decagonal quasicrystals. This analysis
      will be helpful in the study of not only many complex alloys, but also
      quasicrystals.

PMID- 10944257
TI  - Structures and phase transitions of B-Ta2O5 and Z-Ta2O5: two high-pressure forms
      of Ta2O5.
AB  - A sample of Ta2O5, ditantalum pentaoxide, heat-treated in a "toroid"-type high
      pressure chamber at P = 8 GPa and T = 1470 K, was studied by X-ray powder
      diffraction and high-resolution transmission electron microscopy (HRTEM). Two
      high-pressure modifications of Ta2O5, isostructural with B-Nb2O5 and Z-Nb2O5,
      were identified from the X-ray powder pattern. Both structures were refined by
      the Rietveld method from the X-ray diffraction data: B-Ta2O5, a = 12.7853 (4), b
      = 4.8537 (1), c = 5.5276 (2) A, beta = 104.264 (2)degrees, V = 332.45 A3, Z = 4,
      space group C2/c; Z-Ta2O5, a = 5.2252 (1), b = 4.6991 (1), c = 5.8534 (1) A, beta
      = 108.200 (2)degrees, V = 136.53 A3, Z = 2, space group C2. The Z-Ta2O5
      modification is new. The Ta atoms are six-coordinated in B-Ta2O5 and seven
      coordinated in Z-Ta2O5. The two structures are closely related, which makes an
      intergrowth and a transformation between them possible. An idealized model of the
      intergrowth structure has been given. The HRTEM study showed defect-rich B-Ta2O5
      crystals, which could be interpreted as an intergrowth between the B-Ta2O5 and Z
      Ta2O5 phases.

PMID- 10944258
TI  - Synthesis, structure and magnetic properties of tetrakis-mu-carboxylato
      bis(dodecylnicotinato)dicopper(II) complexes; crystal and molecular structure of
      the decyl carboxylate derivative.
AB  - Dodecylnicotinate bis-adducts of binuclear copper carboxylates, of the general
      formula Cu2(O2CC(n-1)H(2n-1))4(C5H4NCOOC12H25)2, were synthesized for n = 10, 12,
      14, 16, 18 and 20, and their crystal structure, thermal behavior and magnetic
      properties studied. The molecular structure of the decyl derivative has been
      determined from single-crystal X-ray diffraction data. The dimer is
      centrosymmetric with the CuII ions in a square-pyramidal coordination with four O
      alkyl O atoms [average d(Cu-O) 1.960 (6) A] in the basal plane and the nicotine N
      atom at apical positions [d(Cu-N) 2.183 (3) A]. The copper ions, 2.615 (1) A
      apart, are bridged by four O-alkyl carboxylate groups. Both the n = 20 and n = 18
      homologues exhibit lamellar phases, which can be related to the supramolecular
      arrangement found in the n = 10 derivative. The magnetic behavior of the decyl
      and octadecyl dimers was studied in the 2-300 K temperature range. They exhibit a
      strong intramolecular antiferromagnetic interaction (Cu-Cu superexchange coupling
      constant J = -347 cm(-1) for the decyl derivative), which can be attributed to a
      large overlap of the metal 3d orbitals and the oxygen lone pair orbitals of the
      linking carboxylate groups.

PMID- 10944259
TI  - Frequency of Z' values in organic and organometallic crystal structures.
AB  - The frequencies of Z' values (formula units per asymmetric crystal unit) are
      documented for organic and organometallic crystal structures, using the Cambridge
      Structural Database. The absolute frequencies of all Z' values reported, relative
      frequencies for certain substance classes, the seven crystal systems and the most
      abundant space groups are given. The three Z' values 1/2, 1 and 2 make up 95.3%
      of all crystal structures. Structures with Z' > 1 occur most frequently with
      nucleosides and nucleotides (20.8%), and with steroids (18.8%).

PMID- 10944260
TI  - Determining the crystal structure of twinned 2-methylpyrazine.
AB  - Although systematic absences and symmetry relations among reflections pointed to
      space group I4(1)22 (one molecule in the asymmetric unit), a direct methods
      solution could only be obtained in I(-)4 (two molecules in the asymmetric unit).
      Refinement in I(-)4 was unsatisfactory until merohedral twinning was taken into
      account. The resulting molecular dimensions are in excellent agreement with
      analogous values in the literature. The molecular arrangement is described.

PMID- 10944261
TI  - Crystal-to-crystal photodimerization of trans-cinnamamides.
AB  - In the crystals of trans-4-methylcinnamamide, C10HT11NO (I), trans-4
      chlorocinnamamide, C9H8ClNO (II), trans-3-(2-thienyl)acrylamide, C7H7NOS (III),
      and trans-cinnamamide, C9H9NO (IV), the shortest intermolecular C...C distances
      between the C=C double bonds are 3.670 (2), 3.632 (2), 3.762 (3) and 4.120 (2) A,
      respectively, for the pair of molecules related by a center of symmetry. The
      structure analysis was also carried out for trans-2-(p-chlorophenyl)-cis4-(p
      chlorophenyl)-1-trans-3-diamidocyclobutane, C18H16Cl2N2O2 (V), which is the alpha
      type photodimer of (II). The NH...O hydrogen-bond networks in (I)-(III) are
      composed of two-dimensional pleated sheets, and those in (IV) and (V) of one
      dimensional flat ribbons. The single crystals of (I), (II) and (IV) were
      photoirradiated with a 250 W ultra-high-pressure mercury lamp through a band-pass
      filter or a long-pass filter for 2-5 h. The photodimer was produced in each
      crystal with retention of the single-crystal form. The populations of the dimers
      were converged to 86.2 (4), 48.4 (6) and 4.5 (2)% in the refinement of the
      crystals after photoirradiation, (I'), (II') and (IV'), respectively. Although
      the intermolecular N-H...O hydrogen-bond network remained in (I') and (II'), the
      network was partly broken in (IV') in the process of photoreaction.

PMID- 10944262
TI  - X-ray studies on crystalline complexes involving amino acids and peptides. XXXV.
      Invariance and variability in amino acid aggregation in the complexes of maleic
      acid with L-histidine and L-lysine.
AB  - The crystal structures of complexes of maleic acid with L-histidine and L-lysine
      have been determined. The two crystallographically independent amino acid
      molecules in the L-histidine complex have different closed conformations, while
      the lysine molecule in its complex has the most favourable conformation
      sterically with an all-trans sidechain trans to the alpha-carboxylate group. The
      maleic acid molecules exist as semi-maleate ions of similar conformation and
      contain a symmetric O...H...O hydrogen bond. Amino acid cations and semi-maleate
      anions aggregate into alternate layers in both the structures. The arrangement of
      molecules in the histidine layer in L-histidine semi-maleate is closer to that in
      the crystals of the free amino acid than in other L-histidine complexes. On the
      other hand, the arrangement of lysine molecules in its semi-maleate complex is
      different from any observed so far. However, the well established characteristic
      interaction patterns involving amino and carboxylate groups still play a major
      role in holding the molecules together in the crystal of the complex.

PMID- 10944263
TI  - A test of crystal structure prediction of small organic molecules.
AB  - A collaborative workshop was held in May 1999 at the Cambridge Crystallographic
      Data Centre to test how well currently available methods of crystal structure
      prediction perform when given only the atomic connectivity for an organic
      compound. A blind test was conducted on a selection of four compounds and a wide
      range of methodologies representing, the principal computer programs currently
      available were used. There were 11 participants who were allowed to propose at
      most three structures for each compound. No program gave consistently reliable
      results. However, seven proposed structures were close to an experimental one and
      were classified as "correct". One compound occurred in two polymorphs, but only
      one form was predicted correctly among the calculated structures. The basic
      problem with lattice energy based methods of crystal structure prediction is that
      many structures are found within a few kJ mol(-1) of the global minimum. The fine
      detail of the force-field methodology and parametrization influences the energy
      ranking within each method. Nevertheless, present methods may be useful in
      providing a set of structures as possible polymorphs for a given molecular
      structure.

PMID- 10944264
TI  - Non-centrosymmetric racemates: space-group frequencies and conformational
      similarities between crystallographically independent molecules.
AB  - DL-Allylglycine (DL-2-amino-4-pentenoic acid, C5H9NO2) yields crystals with
      Pca2(1) symmetry and two crystallographically independent yet pseudo-inversion
      related enantiomers. The distribution among the common space groups of other
      crystalline racemates with more than one molecule in the asymmetric unit has been
      established. The conformational similarities between crystallographically
      independent enantiomers in 114 non-centrosymmetric racemates were quantified
      using the r.m.s. deviation for a molecular superposition. The analysis shows that
      in the majority of crystals the conformations of the crystallographically
      independent molecules are very similar with mean r.m.s. deviation = 0.190 A. In
      almost 80% of the structures the mean r.m.s. deviations is in the interval 0-0.2
      A. It is estimated that racemates constitute 23% of the centrosymmetric organic
      structures in the Cambridge Structural Database.

PMID- 10944265
TI  - Structural relationships in crystals accommodating different stereoisomers of 2
      amino-3-methylpentanoic acid.
AB  - A reinvestigation of the crystal structure of the 1:1 mixture of the two
      racemates DL-isoleucine and DL-allo-isoleucine, with a detailed analysis of
      interatomic distances between alternative side-chain positions, reveals a
      systematic distribution of the four stereoisomers in this crystal. Two different
      molecular chains exist in the crystal and each such chain accommodates a single
      diastereomeric pair only (L-isoleucine:D-allo-isoleucine or D-isoleucine:L-allo
      isoleucine). The crystal is built up by a stacking of such chains in two
      dimensions and three different packing modes for the two types of chains are
      discussed. Crystallization experiments of the two individual racemates in the 1:1
      mixture of DL-isoleucine:DL-allo-isoleucine have been undertaken. The structure
      of the racemate DL-isoleucine is presented. The molecular arrangements in this
      racemate and the 1:1 DL-isoleucine:DL-allo-isoleucine mixture are closely
      related. Furthermore, the spontaneous resolution of enantiomers upon
      crystallization of the other racemate, DL-allo-isoleucine, is rationalized on the
      basis of the aforementioned analysis of interatomic distances in the 1:1 DL
      isoleucine:DL-allo-isoleucine complex. Structural data for a new L-isoleucine: D
      allo-isoleucine complex are also given.

PMID- 10944266
TI  - Electron density and electrostatic properties of two peptide molecules: tyrosyl
      glycyl-glycine monohydrate and glycyl-aspartic acid dihydrate.
AB  - The electron density and electrostatic properties of Tyr-Gly-Gly and Gly-Asp
      molecules have been determined from high-resolution X-ray diffraction data at 123
      K. Topological properties of the charge distribution are discussed and compared
      with those derived from other experimental studies on peptide molecules, and the
      characteristics of the (3,-1) critical points of the C=O, C-N, C-C bonds are
      analysed. Crystal data for Tyr-Gly-Gly: C13H17N3O5.H2O, Mr = 313, orthorhombic,
      P2(1)2(1)2(1), Z = 4, T = 123 +/- 2 K; lattice parameters: a = 7.984 (2), b =
      9.535 (3), c = 18.352 (5) A, V= 1397.1 (6) A3, Dx = 1.49 g cm(-3), mu = 1.2 cm(
      1) for lambdaMo = 0.7107 A. Crystal data for Gly-Asp: C6H10N2O5.2H2O, Mr = 212,
      orthorhombic, P2(1)2(1)2(1), Z = 4, T = 123 +/- 2 K; lattice parameters: a =
      9.659 (1), b = 9.672 (1), c = 10.739 (1) A, V= 1003.3 (4) A3, Dx = 1.40 g cm(-3),
      mu = 1.3 cm(-1) for lambda(Mo)= 0.7107 A.

PMID- 10944267
TI  - Single crystal structure and molecular dynamics analysis of a myo-inositol
      derivative.
AB  - The crystal structure of 5-O-tert-butyldimethylsilyl-3,4-O-carbonyl-1,2-O
      cyclohexylidene-2-oxo-3-oxa-4-bornanylcarbonyl-D-myo-inositol has been studied by
      single-crystal X-ray diffraction at both room temperature and 173 K. At room
      temperature, the tert-butyldimethylsilyl group exhibits dynamical disorder. A
      molecular dynamics simulation was used to model the disorder and this indicates
      that the group librates between two stable conformations in the crystal.
      Approximate relative energies of the different forms and energy barriers for the
      transition were obtained by empirical force field methods. Calculations of the
      thermal motion of the atoms are in good qualitative, but fair to poor
      quantitative agreement with the X-ray data.

PMID- 10944270
TI  - Cerous sodium nitrate monohydrate, Na2Ce(NO3)5.H2O
AB  - The title compound, disodium cerium pentanitrate monohydrate, was synthesized
      from a nitric acid solution of Ce(NO(3))(3).6H(2)O and NaNO(3), and its structure
      has been determined from single-crystal X-ray diffraction data. The structure is
      built from isolated chains of irregular icosahedral [Ce(NO(3))(6)](3-) anions. Na
      atoms and water molecules are located between the chains. The Na coordination
      polyhedra, in the form of a square antiprism or a monocapped square antiprism,
      share common vertices and contribute to the formation of a three-dimensional
      network. Ten nitrate groups act as bridging ligands.

PMID- 10944271
TI  - Silver niobium trioxide, AgNbO3
AB  - The present structure determination of silver niobium trioxide at 291 K was
      performed on a twinned single crystal with a predominant presence [about 93 (1)%]
      of one twin domain. The sample contained traces of V (about 1 atomic %). This
      study confirms that the room-temperature phase of AgNbO(3) is isostructural with
      the room-temperature phase of NaNbO(3), i.e. it is a tilted perovskite.
      Structural deviation in AgNbO(3) from centrosymmetry was not detected in this
      study and its structure was refined in Pbcm, though a previous study indicated
      ferroelectricity below 350 K, in contrast with NaNbO(3).

PMID- 10944272
TI  - Clemizoledichlorocobalt(II).
AB  - The structure of dichloro[1-(p-chlorobenzyl)-2-(1-pyrrolidinylmethyl-N)-1, 3
      benzimidazole-N(3)]cobalt(II), [CoCl(2)(C(19)H(20)ClN(3))], contains a molecule
      of clemizole bound in a bidentate manner to cobalt through its imidazole and
      pyrrolidinyl N atoms, with significantly different Co-N distances of 1.976 (5)
      and 2.126 (5) A, respectively. The geometry around cobalt is distorted
      tetrahedral, with significantly different Co-Cl distances of 2.217 (2) and 2.233
      (2) A, and the pyrrolidinyl ring is disordered.

PMID- 10944273
TI  - Triaqua(oxalato-O,O')oxovanadium(IV) dihydrate
AB  - In the structure of the title compound, [VO(C(2)O(4))(H(2)O)(3)]. 2H(2)O, the V
      atom of the oxovanadium(IV) cation is coordinated to one bidentate oxalate anion
      and three water molecules, resulting in a neutral complex. Two more water
      molecules are not coordinated to the V atoms but are involved in the hydrogen
      bonding network, which consists of ten different hydrogen bonds.

PMID- 10944274
TI  - catena-Poly
AB  - The two title compounds, [Cu(3)(C(6)H(11)O(2))(6)(C(7)H(9)N)(2)](n), (I), and
      [Cu(2)(C(5)H(9)O(2))(4)(C(7)H(9)N)(2)], (II), have chain and finite-molecular
      structures, respectively. In (I), binuclear cage units and mononuclear 2,6
      dimethylpyridine complexes, both of which have inversion centres, are arranged
      alternately and are linked by the carboxylate ions to form one-dimensional chains
      along the a axis. In (II), the binuclear cage unit has an inversion centre and
      the coordination geometry around the Cu atom is typical square pyramidal, with
      2,6-dimethylpyridine at the apical position.

PMID- 10944275
TI  - Bis(1,10-phenanthroline-N,N')(thiosulfato-O, S)nickel(II)-water-methanol
      (1/0.92/1.4) and bis(2,2'-bipyridyl-N, N')(thiosulfato-O,S)nickel(II)-water
      methanol (1/2/0.55)
AB  - The title compounds, [Ni(S(2)O(3))(C(12)H(8)N(2))(2)].0.92H(2)O.1. 4CH(4)O and
      [Ni(S(2)O(3))(C(10)H(8)N(2))(2)].2H(2)O.0.55CH(4)O, are monomeric, containing
      nickel(II) in a distorted octahedral coordination environment provided by the
      four N atoms of two bidentate bipy or phen groups and one S and one O atom from a
      chelating thiosulfate anion. The crystals are highly unstable outside their
      mother liquors and are stabilized in solution by a not fully determined number of
      water and methanol solvate molecules. The phenanthroline structure includes two
      independent moieties related by a non-crystallographic inversion center. The
      thiosulfate anions display the usual S-O lengthening found when the anion acts in
      a bidentate mode.

PMID- 10944276
TI  - [1,3-Bis(diphenylphosphino)propane]trichlorooxorhenium(V).
AB  - Trichlorooxo[1,3-propanediylbis(diphenylphosphine)-P,P ']rhenium(V),
      [ReCl(3)O(C(27)H(26)P(2))], crystallizes with four formula units per unit cell.
      The crystal structure consists of neutral complexes of [ReOCl(3)(dppp)] [dppp is
      1,3-bis(diphenylphosphino)propane] packed by H.pi-ring interactions. The Re atom
      is octahedrally coordinated to the oxo anion, three Cl atoms and two P atoms from
      the dppp ligand. The six-membered ring formed by the bidentate dppp ligand and
      the rhenium metal centre is in a chair conformation. The title compound is an
      intermediate in the synthesis of bis(dppp) complexes of rhenium.

PMID- 10944277
TI  - Dichlorobis(3,5-dimethylpyrazole-N2)methylphenyltin(IV)
AB  - The title compound, [SnCl(2)(CH(3))(C(6)H(5))(C(5)H(8)N(2))(2)], was obtained by
      reaction of dichloromethylphenyltin(IV) and 3, 5-dimethylpyrazole (dmpz) in
      chloroform, and was recrystallized from acetone. The structure consists of
      octahedral all-trans [SnMePhCl(2)(dmpz)(2)] molecules, with the Sn atom
      coordinated to two C [Sn-C 2.127 (5) and 2.135 (4) A], two Cl [Sn-Cl 2.5753 (8)
      A] and two N atoms [Sn-N 2.357 (3) A]. The dmpz ligands, bound to the metal
      through their unprotonated N atoms, form weak intra- and intermolecular hydrogen
      bonds with the Cl ligands via their NH groups, giving rise to a polymeric chain
      along the c axis.

PMID- 10944278
TI  - Diaquabis(4,5-dihydro-1,2,4-triazolo
AB  - The title compound, [Ni(NCS)(2)(C(5)H(4)N(4)O)(2)(H(2)O)(2)], crystallizes in the
      triclinic space group P-1. The molecular unit contains two neutral molecules of
      4,5-dihydro-1,2,4-triazolo[1, 5-a]pyrimidin-5-one (5HtpO) coordinated through the
      N atom in position 3, two thiocyanate ligands coordinated through their N atoms
      and two water molecules completing an octahedral environment around the Ni(II)
      ion, which lies on a centre of inversion. The structure is stabilized by hydrogen
      bonding. Distances in the coordination sphere are Ni-N3(5HtpO) 2.132 (2), Ni
      O(water) 2.085 (2) and Ni-N(thiocyanato) 2.040 (2) A.

PMID- 10944279
TI  - Transition metal complexes with thiosemicarbazide-based ligands. XV. A square
      pyramidal NiII complex with an asymmetric coordination of 2, 6-diacetylpyridine
      bis(S-methylisothiosemicarbazone)
AB  - The title compound, [diacetylpyridine bis(S
      methylisothiosemicarbazonato)]iodonickel(II), [Ni(C(13)H(18)N(7)S(2))I], is the
      first example of a complex involving the (2)N coordination of the
      isothiosemicarbazide moiety. 2,6-Diacetylpyridine bis(S
      methylisothiosemicarbazone), as a potentially pentadentate ligand (N(5)), is
      coordinated as a tetradentate species, whereby one (deprotonated)
      isothiosemicarbazide moiety is coordinated in the usual way ((1)N(4)N), but the
      other (neutral) is bonded via the (2)N atom only, the fourth ligator being the
      pyridine nitrogen. The difference in coordination mode of the
      isothiosemicarbazide moiety is reflected in the (1)N-(2)N bond lengths of 1.359
      (4) and 1.379 (3) A in the deprotonated and undeprotonated moieties,
      respectively. The structure contains three fused chelate rings in a 5:5:6
      arrangement. The six-membered ring has a non-planar conformation.

PMID- 10944280
TI  - (N,N-Diisopropyldithiocarbamato-S, S')bis(triphenylphosphine-P)gold(I) butane
      solvate
AB  - In the crystal structure of the title complex,
      [Au(C(7)H(14)NS(2))(C(18)H(15)P)(2)].C(4)H(10), the Au atom is in a distorted
      tetrahedral environment consisting of the two P atoms of the triphenylphosphine
      ligands and the two S atoms of the diisopropylthiocarbamate ligand. The molecular
      structure and packing are stablized by van der Waals interactions.

PMID- 10944281
TI  - trans-Dichloro(1,5,9,13-tetramethyl-1,5,9, 13-tetrazacyclohexadecane
      kappa4N)ruthenium(III) triiodide
AB  - In the title complex, [RuCl(2)(C(16)H(36)N(4))]I(3), the overall symmetry of the
      centrosymmetric cation is approximately C(2h) and the I(-3) anions are slightly
      asymmetric. The I.I distance is 4.313 (1) A. The cations and the linear anions
      are arranged in alternate layers and thus form the intercalating structure.

PMID- 10944283
TI  - trans-Chloro(2-nitrobenzenethiolato-S)bis(triphenylphosphine-P)pallad ium(II)
      monoacetone solvate
AB  - Molecules of the title compound, [PdCl(C(6)H(4)NO(2)S)(PPh(3))(2)]. C(3)H(6)O,
      exhibit a slight distortion from exact planarity at the Pd atom towards
      tetrahedral, with P-Pd-P and Cl-Pd-S angles of 174. 98 (3) and 174.19 (3)
      degrees, respectively. The Pd-Cl and Pd-S bonds are, respectively, long [2.3550
      (11) A] and short [2.3020 (12) A] for their types; the S-C bond is also very
      short [1.744 (4) A]. The solvating acetone molecule is linked to one of the
      phosphine ligands by means of a C-H.O hydrogen bond.

PMID- 10944282
TI  - Tetraaquabis[2-(4-pyridyl)ethanesulfonato-N]zinc(II).
AB  - The title compound, [Zn(C(7)H(8)NO(3)S)(2)(H(2)O)(4)], has an octahedral
      coordination around the central Zn atom composed of two axial N atoms from the
      pyridine ligands and four equatorial O atoms of water molecules, forming a
      monomeric centrosymmetric complex. The two Zn-N bond distances are 2.102 (3) A,
      while the four Zn-O bond distances range from 2.114 (2) to 2.167 (2) A. Packing
      is determined by hydrogen bonds formed by the water molecules. The sulfonate
      group does not take part in coordination to the Zn atom.

PMID- 10944284
TI  - trans-Bis(diethanolamine)bis(isothiocyanato)nickel(II)
AB  - In the neutral title complex, trans-bis(2,2'-iminodiethanol-N,
      O)bis(isothiocyanato)nickel(II), [Ni(NCS)(2)(C(4)H(11)NO(2))(2)], the
      isothiocyanate ions and the diethanolamine molecules act as monodentate and
      bidentate ligands, respectively. The Ni(II) ion exhibits a distorted octahedral
      configuration with crystallographically imposed inversion symmetry and N(NCS)-Ni
      N(amine) and N(NCS)-Ni-O(amine) bond angles of 88.78 (10) and 89.44 (10) degrees,
      respectively. The Ni-N bond distances are in the range 2.069 (3)-2.096 (2) A. The
      molecules are linked by hydrogen bonds to form a three-dimensional infinite
      lattice.

PMID- 10944285
TI  - (Benzoylacetonato)chloro(1,10-phenanthroline)copper(II)
AB  - The crystal structure of the title compound, chloro(1, 10-phenanthroline-N,N')(1
      phenyl-1,3-butanedionato-O,O')copper(II), [CuCl(C(10)H(9)O(2))(C(12)H(8)N(2))],
      has been determined. The Cu(II) ion displays a distorted square-pyramidal
      coordination, being linked to the two O atoms of the benzoylacetonate ligand and
      the two N atoms of the 1,10-phenanthroline ligand in the basal plane, and the Cl
      atom in the apical site. TheCu-N, Cu-O and Cu-Cl bond lengths are 2.043 (2)/2.025
      (2), 1.914 (2)/1.941 (2) and 2.485 (1) A, respectively.

PMID- 10944286
TI  - Bis
AB  - In the title compound, [Zn(C(8)H(10)N(3)O(2))(2)], the Zn atom displays a highly
      distorted octahedral coordination involving O and N atoms of two bidentate planar
      ligands approximately orthogonal to each other; the dihedral angle between the
      ligand planes is 84.95 (4) degrees. The ligand molecules show great asymmetry in
      their bonding to the Zn(2+) ion, with Zn-O bond distances ranging between 2.056
      (2) and 2.534 (2) A. The planar phenyl ring and the trigonal-planar geometry
      about the triazene N atom bonded to the phenyl ring suggest a resonance
      interaction extending over adjacent atoms.

PMID- 10944287
TI  - Bis
AB  - The geometry about the Ru atom in the title compound,
      [Ru(C(9)H(9)N)(2)(C(92)H(108)N(4)O(24))], is approximately tetragonal and the
      porphyrin ring is nearly planar, while the C-N-R angles [169.3 (3) and 163.9 (3)
      degrees ] of the isocyanide ligands in the complex are different from the value
      of 180 degrees expected in the free ligand.

PMID- 10944289
TI  - Bis(&mgr;-hexamethylenetetramine)bis(aquadibromocadmium)diaquadibromo cadmium
      dihydrate
AB  - The title compound, poly[[diaquadibromocadmium-&mgr;-(1,3,5, 7
      tetraazatricyclo[3.3.1.1(3, 7)]decane-N(1):N(5))-aquacadmium-di-&mgr;-bromo
      aquacadmium-&mgr;-(1, 3,5,7-tetraazatricyclo[3.3.1.1(3, 7)]decane-N(1):N(5))-di
      &mgr;-bromo] dihydrate], [Cd(3)Br(6)(C(6)H(12)N(4))(2)(H(2)O)(4)].2H(2)O, is made
      up of two-dimensional neutral rectangular coordination layers. Each rectangular
      subunit is enclosed by a pair of Cd(3)(&mgr;(2)-Br)(6)(H(2)O)(3) fragments and a
      pair of (&mgr;(2)-hmt)Cd(H(2)O)(2)Br(2)(&mgr;(2)-hmt) fragments as sides (hmt is
      hexamethylenetetramine). The unique Cd(II) atom in the Cd(2)Br(2) ring in the
      Cd(3)(&mgr;(2)-Br)(6)(H(2)O)(3) fragment is in a slightly distorted octahedral
      CdNOBr(4) geometry, surrounded by one hmt ligand [2.433 (5) A], one aqua ligand
      [2.273 (4) A] and four Br atoms [2.6409 (11)-3.0270 (14) A]. The Cd(II) atom in
      the (&mgr;(2)-hmt)Cd(H(2)O)(2)Br(2)(&mgr;(2)-hmt) fragment lies on an inversion
      center and is in a highly distorted octahedral CdN(2)O(2)Br(2) geometry,
      surrounded by two trans-related N atoms of two hmt ligands [2.479 (5) A], two
      trans-related aqua ligands [2.294 (4) A] and two trans-related Br atoms [2.6755
      (12) A]. Adjacent two-dimensional coordination sheets are connected into a three
      dimensional network by hydrogen bonds involving lattice water molecules, and the
      aqua, bromo and hmt ligands belonging to different layers.

PMID- 10944288
TI  - A mixed-valence iron complex of the antitumour drug 6-mercaptopurine: tris(6
      mercaptopurine)iron(II) tetrachloroferrate(III) chloride.
AB  - Single crystals of the title complex, tris(1, 6-dihydro-9H-purine-6-thione
      N(7),S)iron(II) tetrachloroferrate(III) chloride,
      [Fe(C(5)H(4)N(4)S)(3)][FeCl(4)]Cl, were grown on the surface of solid 6
      mercaptopurine monohydrate pellets in a solution of iron(III) chloride. The
      solution of the hexagonal structure required the application of twin refinement
      techniques. All the component ions lie on threefold rotation axes. The complex
      contains distorted octahedral [Fe(C(5)H(4)N(4)S)(3)](2+) cations with three N7/S6
      chelating neutral 6-mercaptopurine ligands, tetrahedral [FeCl(4)](-) anions with
      a mean Fe-Cl distance of 2.189 (1) A, and free chloride ions.

PMID- 10944290
TI  - fac,trans-
AB  - The crystal structure of the heterobimetallic title compound,
      [ReRuCl(C(10)H(16)As(2))(2)(C(10)H(8)N(2))(2)(CO)(3)](PF(6))(2). 2C(3)H(6)O, is
      described. Both metal centres have pseudo-octahedral coordination geometries,
      with a facial arrangement of the carbonyl ligands at Re(I) and a trans
      disposition of the diarsine ligands at Ru(II). The dihedral angle between the
      pyridyl rings of the 4, 4'-bipyridine bridging ligand is 13.9 (6) degrees.

PMID- 10944292
TI  - Di-&mgr;-bromo-bis
AB  - Di-2-pyridyl ketone reacts with CdBr(2) in water to form the title
      centrosymmetric dinuclear complex, [Cd(2)Br(4)(C(11)H(10)N(2)O(2))(2)].3H(2)O, in
      which each metal atom is coordinated by an N,O,N'-chelated di-2
      pyridylmethanediol ligand, two bridging bromo ligands and one terminal bromo
      ligand in a distorted octahedral geometry.

PMID- 10944291
TI  - Linear chains in polymeric dicyclohexylammonium tributyl(4-oxo-4H-pyran-2,6
      dicarboxylato)stannate and methylphenylammonium tributyl(pyridine-2,6
      dicarboxylato)stannate containing trigonal bipyramidal tin.
AB  - catena-Poly[dicyclohexylammonium [tributyltin-mu-(4-oxo-4H-pyran-2,6
      dicarboxylato-O(2):O( 6))]], (C(12)H(24)N)[Sn(C(7)H(2)O(6))(C(4)H(9))(3)],
      consists of 4-oxo-4H-pyran-2,6-dicarboxylato groups that axially link adjacent
      tributyltin units into a linear polyanionic chain. The ammonium counter-ions
      surround the chain, and each cation forms a pair of hydrogen bonds to the double
      bond carbonyl O atoms of the same dianionic group. The chain propagates in a
      zigzag manner along the c axis of the monoclinic cell. In catena
      poly[methyl(phenyl)ammonium [tributyltin-mu-(pyridine-2,6-dicarboxylato
      O(2):O(6))]], (C(7)H(10)N)[Sn(C(7)H(3)NO(4))(C(4)H(9))(3)], the pyridine-2, 6
      dicarboxylato groups also link the tributyltin groups into a chain, but the
      hydrogen-bonded chain propagates linearly on the ac face of the monoclinic cell.

PMID- 10944293
TI  - A combinatorial chemistry approach to new materials for non-linear optics. I.
      Five schiff bases
AB  - A combinatorial chemistry approach has been used to synthesize an array of Schiff
      bases, five of which, namely N-[(E, 2E)-3-(4-methoxyphenyl)-2-propenylidene]-3
      nitroaniline, C(16)H(14)N(2)O(3), (1a), N-[(E, 2E)-3-(4-methoxyphenyl)-2
      propenylidene]-4-nitroaniline, C(16)H(14)N(2)O(3), (2a), N-(E, 2E)-3-[4
      (dimethylamino)phenyl]-2-propenylidene-3-nitroaniline, C(17)H(17)N(3)O(2), (1b),
      N-(E, 2E)-3-[4-(dimethylamino)phenyl]-2-propenylidene-4-nitroaniline,
      C(17)H(17)N(3)O(2), (2b), and N-(E, 2E)-3-[4-(dimethylamino)phenyl]-2
      propenylidene-2-methyl-4-nitroanil ine, C(18)H(19)N(3)O(2), (3b), have been
      structurally characterized. A stack structure is observed for (1a) and (1b) in
      the crystal phase. Experimental and calculated molecular structures are discussed
      for these compounds which belong to a chemical class having potential
      applications as non-linear optical materials.

PMID- 10944294
TI  - A combinatorial chemistry approach to new materials for non-linear optics. II. 4
      (Dimethylamino)cinnamaldehyde and a molecular complex of 4-methoxycinnamaldehyde
      with 2,4-dinitroaniline
AB  - The combinatorial chemistry approach has been used to synthesize an array of
      Schiff bases. The structures of five of these Schiff bases have been confirmed by
      X-ray analysis [Nesterov, Timofeeva, Borbulevych, Antipin & Clark (2000). Acta
      Cryst. C56, 971-975]. In two cases, the reaction conditions were not sufficient
      to obtain the products in question. In one case, a molecular complex,
      C(10)H(10)O(2).C(6)H(5)N(3)O(4), of the starting products 4-methoxycinnamaldehyde
      and 2,4-dinitroaniline was found. X-ray analysis revealed hydrogen-bond formation
      between the molecules of these reagents in the crystal. In the other case, X-ray
      analysis demonstrated that no chemical reaction occurred under the reaction
      conditions, and only one starting reagent, 4-(dimethylamino)cinnamaldehyde,
      C(11)H(13)NO, was found in the precipitate.

PMID- 10944295
TI  - (24R)-24,25-Dihydroxycycloartan-3-one.
AB  - In the title compound, C(30)H(50)O(3), the three six-membered rings adopt chair,
      twist and twist-boat conformations. The five-membered ring is in a slightly
      distorted envelope conformation. The substituent on the five-membered ring is in
      an extended conformation, with its two hydroxyl O atoms forming an intramolecular
      hydrogen bond. One of these O atoms also forms an intermolecular hydrogen bond
      with the oxygen of the carbonyl group in a neighbouring molecule.

PMID- 10944296
TI  - (4S,5S)-(+)-4-Hydroxymethyl-2,5-diphenyloxazoline
AB  - The absolute configuration of the title compound, alternatively called (+)-(4,5
      dihydro-2,5-diphenyloxazol-4-yl)methanol, C(16)H(15)NO(2), has been confirmed as
      4S,5S. The hydroxymethyl group and phenyl ring at the asymmetric C atoms exhibit
      beta and alpha orientations, respectively. The exocyclic C-C bonds at the
      asymmetric C atoms are mutually anticlinal (-ac). The hydroxyl group and the N
      atom of the oxazoline ring are involved in an intermolecular hydrogen bond
      leading to chains of molecules.

PMID- 10944297
TI  - Triterpenoide. XX. 3beta-acetoxy-12-oxo-18beta-olean- und 3beta-acetoxy-12,19
      dioxo-9(11), 13(18)-oleandien-28-saure-methylester
AB  - The structures of methyl 3beta-acetoxy-12-oxo-18beta-olean-28-oate
      [C(33)H(52)O(5), (I)] and methyl 3beta-acetoxy-12, 19-dioxoolean-9(11),13(18)
      dien-28-oate [C(33)H(46)O(6), (II)] are described. In (I), all rings are in the
      chair conformation, rings D and E are cis and the other rings trans-fused. In
      compound (II), only rings A and E are in the chair conformation, ring B has a
      distorted chair conformation, ring C a distorted half-boat and ring D an
      insignificantly distorted half-chair conformation.

PMID- 10944298
TI  - Benzyltriphenylphosphonium glutaconaldehyde
AB  - The title compound, C(25)H(22)P(+).C(5)H(5)O(2)(-), crystallizes in space group
      P2(1)/c. The phosphonium cations form zigzag chains with P.P distances of 6.475
      (1) and 8.287 (2) A, and are related by inversion centres. Two types of
      attractive edge-to-face phenyl interactions exist, resulting in a dominant
      supramolecular motif. The glutaconaldehyde anions occupy the interchain spacing
      and hold adjacent chains together via multiple C-H.O hydrogen bonds. The bond
      length alternation, a parameter which reveals the non-linear optical efficiency
      at the molecular level, is optimized in the chromophore anion.

PMID- 10944299
TI  - 2'-Deoxy-5-methylisocytidine.
AB  - In the title compound, 2-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5
      methylpyrimidin++ +-4 (1H)-one, C(10)H(15)N(3)O(4), the conformation of the N
      glycosidic bond is syn and the 2-deoxyribofuranose moiety adopts an unusual
      (O)T(1) sugar pucker. The orientation of the exocyclic C4'-C5' bond is +sc
      (+gauche).

PMID- 10944301
TI  - Piv-Propsi
AB  - The pseudodipeptide, (S)-N-isopropyl [N-(pivaloyl)pyrrolidin-2
      yl]methylaminooxyacetamide, C(15)H(29)N(3)O(3), adopts a global extended
      conformation with the hydroxylamine group in the g(+)/g(-) structure. The C
      terminal amide NH interacts intramolecularly with the hydroxylamine O atom. Both
      NH bonds of each molecule are hydrogen bonded to the C-terminal amide carbonyl of
      a neighbouring molecule.

PMID- 10944300
TI  - (E)-2-[2-(1-Naphthyl)vinyl]-3-tosyl-2,3-dihydro-1,3-benzothiazole.
AB  - The title compound, C(26)H(21)NO(2)S(2), which consists of a benzothiazole
      skeleton with alpha-naphthylvinyl and tosyl groups at positions 2 and 3,
      respectively, was prepared by palladium-copper-catalyzed heteroannulation. The E
      configuration of the molecule about the vinyl C=C bond is established by the
      benzothiazole-naphthyl C-C-C-C torsion angle of 177.5 (4) degrees. The five
      membered heterocyclic ring adopts an envelope conformation with the Csp(3) atom
      0.380 (6) A from the C(2)NS plane. The two S-C [1.751 (4) and 1.838 (4) A] and
      two N-C [1.426 (5) and 1.482 (5) A] bond lengths in the thiazole ring differ
      significantly.

PMID- 10944302
TI  - Inclusion of HNEt3+ in an acyclic tetraphenolate
AB  - The acyclic tetraphenolic derivative 2, 2'-methylenebis[6-(3-tert-butyl-2-hydroxy
      5-methylbenzyl)-4-methylphe nol] reacts with excess triethylamine in acetonitrile
      to form a molecular complex, i.e. triethylammonium 2-(3-tert-butyl-2-hydroxy-5
      methylbenzyl)-6-[3-(3-tert-butyl-2-hydrox y-5-methylbenzyl)-2-hydroxy-5
      methylbenzyl]-4-methylphenolate acetonitrile solvate,
      C(6)H(16)N(+).C(39)H(47)O(4)(-).C(2)H(3)N, where the organic HNEt(3)(+) cation is
      included in the partial cone defined by the aromatic faces of the acyclic
      polyphenolate.

PMID- 10944303
TI  - 3-Nitro-1-nitromethyl-1H-1,2,4-triazole
AB  - The title compound, C(3)H(3)N(5)O(4), consists of three planar fragments twisted
      in relation to each other, namely a triazole ring, a nitromethylene group and a
      nitro group. Molecular conformation analysis shows that the first stage of
      thermal decomposition is a breakage of the H(2)C-NO(2) bond. There are essential
      conformational differences in the molecule in comparison with semi-empirical
      calculations.

PMID- 10944304
TI  - Tetrakis(3,4-ethylenedioxy-2-thienyl)silane carbon tetrachloride solvate
AB  - The structure of tetrakis(3,4-ethylenedioxy-2-thienyl)silane carbon tetrachloride
      solvate, Si(C(6)H(5)O(2)S)(4).CCl(4), has been determined in the
      noncentrosymmetric space group I-4. The Si and C atoms of the CCl(4) are located
      on the fourfold inversion axes. The Si atom has a tetrahedral geometry. The
      thiophene ring in the 3, 4-ethylenedioxythiophene group is nearly planar to
      within 0.005 A, and the ethylenedioxy moiety is in a half-chair conformation.

PMID- 10944305
TI  - (M)- and (P)-8-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]-8-methyl-8, 9-dihydro
      7H-dinaphth[2,1-c:1',2'-e]azepinium bromide solvates.
AB  - The title compounds are diastereoisomers with antipodean axial chirality. The M
      isomer crystallizes as a (1/3) acetone solvate, C(32)H(30)NO(+).Br(-).3C(3)H(6)O,
      while the P isomer crystallizes as a (1/1) dichloromethane solvate,
      C(32)H(30)NO(+).Br(-).CH(2)Cl(2). In each structure, O-H.Br hydrogen bonds link
      the cations and anions to give ion pairs. The seven-membered azepinium ring
      adopts the usual twisted-boat conformation and its ring strain causes a slight
      curvature of the plane of each naphthyl ring.

PMID- 10944306
TI  - Dimethyl (1-methyl-1,3-benzimidazol-5-yl)aminomethylenepropanedioate monohydrate.
AB  - In the title compound, C(14)H(15)N(3)O(4).H(2)O, there is a strong conjugation
      push-pull effect across the central double bond, as reflected in the molecular
      dimensions and the planarity of the enaminone portion of the molecule. The
      molecule has an intramolecular hydrogen bond between the NH and CO groups in the
      Z configuration, adopting the chelated form. The two pi systems of the molecule
      (1-methylbenzimidazole and enaminone) are deconjugated and tilted with respect to
      each other by 15.6 (2) degrees. The solvent water molecule is hydrogen bonded to
      the N(1) atom of the 1-methylbenzimidazolyl group.

PMID- 10944307
TI  - 1-[2-(1-Hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl]dimethylammonium chloride
      (venlafaxine hydrochloride).
AB  - The crystal structure of racemic Venlafaxine hydrochloride,
      C(17)H(28)NO(2)(+).Cl(-), consists of two types of parallel chains formed by
      translated Venlafaxine(+) cations, hydrogen bonded by Cl(-) anions, and
      characterized by the opposite chirality of their constituent molecules. These
      chains organize in two different types of broad layers of opposite handedness,
      related by a glide plane.

PMID- 10944308
TI  - 1,2-Dibenzoylhydrazine
AB  - In the crystal structure of the title compound, C(14)H(12)N(2)O(2), the molecule
      lies about a twofold axis; two carbonyl groups and the H atoms of the N-N bond
      are in a trans orientation with respect to each other. In the crystal, each
      molecule is linked to the other and vice versa by intermolecular N-H.O hydrogen
      bonds between the amide hydrogen and the O atoms of neighbouring molecules to
      form two ten-membered rings, each of which has the graph-set motif C4R(2)(2)(10).
      This extends as a polymeric chain along the c axis.

PMID- 10944309
TI  - p-methoxybenzaldehyde benzoylhydrazone monohydrate
AB  - The crystal structure of the title compound, C(15)H(14)N(2)O(2). H(2)O, is in the
      keto tautomeric form and the configuration at the azomethine C=N double bond is
      E. The molecule is non-planar, with a dihedral angle of 27.3 (1) degrees between
      the aromatic rings. The crystal structure is stabilized by extensive hydrogen
      bonding involving the water molecule and hydrazone moiety.

PMID- 10944310
TI  - 4-Hydroxy-3-methoxybenzaldehyde 4,5-diazafluoren-9-ylidenehydrazone
AB  - The whole molecule of the title compound, C(19)H(14)N(4)O(2), is essentially
      planar, with a highly conjugated pi system. In the crystal, the molecules are
      packed as chains along the [011] direction connected by O-H.N intermolecular
      hydrogen bonds.

PMID- 10944312
TI  - 3,6,9,16,19,22-Hexaazatricyclo
AB  - In the title macrocyclic polyamine, C(24)H(38)N(6).5H(2)O, the centrosymmetric
      polyamine molecules are stacked in rows, and between these molecules there are
      channels along the a axis. The intermolecular hydrogen bonds formed between the
      water and polyamine, together with those formed between water molecules, generate
      an extensive hydrogen-bonding network.

PMID- 10944311
TI  - 4,5-Diazafluoren-9-one benzoylhydrazone monohydrate.
AB  - The title compound, C(18)H(12)N(4)O.H(2)O, adopts the keto tautomeric form and
      the azomethine C=N double bond is in the E configuration. The dihedral angle
      between the planes of the diazafluorene moiety and the phenyl ring is 11.3 (1)
      degrees. In the solid state, the molecules form infinite chain-like structures
      via O-H.N hydrogen bonds involving the water molecules and diazafluorene
      moieties.

PMID- 10944313
TI  - Hydrogen bonding and C-H.O interactions in 3-(3-aminophthalimido)phthalic acid
      dihydrate
AB  - The title compound, C(16)H(10)N(2)O(6).2H(2)O, crystallized in the
      centrosymmetric triclinic space group P-1 with one organic molecule and two water
      molecules as the asymmetric unit. Eight intermolecular hydrogen bonds have
      donor.acceptor distances in the range 2.602 (2)-3.289 (2) A, with angles in the
      range 137 (2)-177 (2) degrees. These generate a three-dimensional hydrogen-bond
      network. There is a single intramolecular hydrogen bond. There are six
      significant intermolecular C-H.O interactions with H.O distances in the range 2.
      39-2.74 A, and C-H.O angles in the range 131-157 degrees.

PMID- 10944314
TI  - C-H.O interactions in diethyl 5,5',6,6'-tetramethylbiphenyl-2, 2'-dicarboxylate
      at 193 K
AB  - The title compound, C(22)H(26)O(4), crystallized in the centrosymmetric space
      group P-1 with one molecule as the asymmetric unit. Three leading intermolecular
      C-H.O interactions have H.O distances of 2.71, 2.73 (2) and 2.71 (2) A and C-H.O
      angles of 167, 137.0 (15) and 163.1 (12) degrees. These interactions form ring
      and chain patterns. The biphenyl twist angle is 79.95 (6) degrees.

PMID- 10944315
TI  - 1H-Pyrrolo[2,3-b]pyridine-3-acetic acid as a molecular probe for use in auxin
      physiology.
AB  - The structural characterization of 1H-pyrrolo[2, 3-b]pyridine-3-acetic acid
      (alternative name: 7-azaindole-3-acetic acid), C(9)H(8)N(2)O(2), reveals similar
      molecular geometry, i.e. with the side chain perpendicular to the 7-azaindole
      ring, to that of the natural plant growth hormone indole-3-acetic acid (auxin)
      and its alkylated and halogenated derivatives.

PMID- 10944316
TI  - 2-(4-Methoxyphenylazo)-4-phenylphenol
AB  - The crystal structure of the title compound, C(19)H(16)N(2)O(2), displays a trans
      configuration of the azo moiety, which forms an intramolecular O-H.N=N hydrogen
      bond. The H.N and O.N distances are 1.81 (3) and 2.581 (4) A, respectively. The
      azobenzene moiety is approximately planar, and has a dihedral angle of ca 23
      degrees with the substituted phenyl group.

PMID- 10944317
TI  - Comparison of the two anomers of methyl 2-(N-benzylamino)-2, 3-dideoxy-4,6-O
      phenylmethylene-3-C-phenylsulfonyl-D-glucopyranoside
AB  - The title compounds, the alpha and beta anomers of methyl 2-(N-benzylamino)-2,3
      dideoxy-4, 6-O-phenylmethylene-3-C-phenylsulfonyl-D-glucopyranoside,
      C(27)H(29)NO(6)S, belong to the class of deoxyamino-sugars prepared by the
      addition of amines at C2. The endocyclic bond lengths of the pyranose ring in the
      alpha anomer are shorter than the corresponding bonds in the beta anomer. The
      pyranose ring is in the chair form in the former, while it is in the boat form in
      the latter. These observed differences could be attributed to the C2 substitution
      of a bulky group. The phenylsulfonyl and benzylamino groups are in equatorial
      positions in the alpha anomer, while the benzylamino group is axial in the beta
      anomer.

PMID- 10944318
TI  - Triphenylmethanol-triphenylphosphine oxide (1/1)
AB  - In the crystalline 1:1 molecular complex of triphenylmethanol (TPMeOH) and
      triphenylphosphine oxide (TPPO), C(19)H(16)O. C(18)H(15)OP, molecular dimers are
      formed which are linked by O-H. O=P hydrogen bonds. The dimers are aligned by
      sixfold phenyl embraces to form columns. The structure is disordered with half a
      dimer per asymmetric crystal unit, i.e. with only one molecular site which is
      half-occupied by both TPMeOH and TPPO.

PMID- 10944319
TI  - YC-1, an activation inductor of soluble guanylyl cyclase.
AB  - The crystal structure of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole,
      C(19)H(16)N(2)O(2), showed that the furan O and indazole N atoms lie on the same
      face of the molecule. The crystal packing consists of intermolecular hydrogen
      bonding, and indazole-indazole and indazole-phenyl interactions.

PMID- 10944320
TI  - Two key chiral intermediates in a new 4-hydroxyisoleucine synthesis.
AB  - We present the crystal and molecular structure of two key compounds of a new
      synthesis strategy for isomers of natural (2S,3R, 4S)-4-hydroxyisoleucines,
      2,3,5,6,7, 8-hexahydro-3-(1-hydroxy-1-methyl-2-oxopropyl)-6,8-methano-7,7, 8a
      trimethyl-5H-1,4-benzoxazin-2-one, C(16)H(23)NO(4), and 2,3,5,6,7, 8-hexahydro-3
      (1-methyl-2-oxopropyl)-6,8-methano-7,7, 8a-trimethyl-5H-1,4-benzoxazin-2-one,
      C(16)H(23)NO(3). A new optically pure chiral oxazinone auxiliary derived from
      (1R,2R, 5R)-2-hydroxypinan-3-one was used.

PMID- 10944321
TI  - (1E,3E,5E)-1,2,3,4,5,6-Hexafluoro-1,6-diphenylhexatriene
AB  - The title triene, C(18)H(10)F(6), was prepared via the Pd(0) coupling reaction of
      (E)-(1,2-difluoro-1, 2-ethenediyl)bis(tributylstannane) with (Z)-beta-iodo-alpha,
      beta-difluorostyrene in N,N'-dimethylformamide/tetrahydrofuran. The crystal
      structure shows the product to be the 1E,3E,5E isomer. Due to steric interactions
      between F atoms, the double bonds are not coplanar. The planes defined by the two
      terminal double bonds are almost perpendicular.

PMID- 10944322
TI  - O-Isopropyl N-(2-furoyl)thiocarbamate
AB  - The title compound, C(9)H(11)NO(3)S, has crystallographic mirror symmetry, occurs
      in the thiocarbamate form and is stabilized in an s-cisoid,s-transoid
      conformation with respect to the C-N-C group. There are two intramolecular
      hydrogen bonds, one between the H atom of the N-H group and the O atom of the
      furan ring, and the other between the H atom of the secondary carbon of the
      isopropyl group and the S atom. The packing of the molecules is assumed to be
      dictated by van der Waals interactions.

PMID- 10944323
TI  - 2-[(4-Hydroxyphenyl)iminomethyl]thiophene.
AB  - The molecular structure of the title compound, C(11)H(9)NOS, has three planar
      moieties, two of which are rings, namely the hydroxyphenyl and the thiophene,
      with an angle of 20.76 (10) degrees between them. The crystal structure is
      stabilized by an O-H.N hydrogen bond and by C-H.O intermolecular interactions.
      The C.O intermolecular contact distance is 3.443 (2) A.

PMID- 10944324
TI  - 2,4-Bis(alpha,alpha-dimethylbenzyl)phenol
AB  - The structure of the title compound, 2, 4-bis(1-methyl-1-phenylethyl)phenol,
      C(24)H(26)O, was found to have a torsion angle of 129.95 (13) degrees for the C-C
      bond that connects the benzyl carbon to the phenol ring ortho to the OH group. A
      value of approximately 50 degrees was expected from molecular mechanics
      calculations. Intermolecular interactions, in particular O-H.O and edge-face pi
      bonding, may contribute to this discrepancy. Intramolecular O-H.pi bonding is
      also observed.

PMID- 10944325
TI  - Ranitidine hydrochloride, a polymorphic crystal form.
AB  - In the title compound, dimethyl(?5-[2-(1-methylamino-2
      nitroethenylamino)ethylthiometh yl]-2- furyl?methyl)ammonium chloride,
      C(13)H(23)N(4)O(3)S(+).Cl(-), protonation occurs at the dimethylamino N atom. The
      ranitidine molecule adopts an eclipsed conformation. Bond lengths indicate
      extensive electron delocalization in the N,N'-dimethyl-2-nitro-1, 1-ethenediamine
      system of the molecule. The nitro and methylamino groups are trans across the
      side chain C=C double bond, while the ethylamino and nitro groups are cis. The
      Cl(-) ions link molecules through hydrogen bonds.

PMID- 10944326
TI  - NEt4OH.5H2O containing hydroxide-water layers
AB  - In the title compound, tetraethylammonium hydroxide pentahydrate,
      C(8)H(20)N(+).OH(-).5H(2)O, layers of approximately hexagonally close-packed
      NEt(4)(+) cations and anionic layers of hydroxide and water molecules are stacked
      alternately along the b axis. All hydroxide and water H atoms are in ordered
      positions, giving rise to a network of hydrogen bonds [O.O 2.633 (1)-2.947 (2) A]
      with four- and six-membered rings. The hydroxide ion accepts four hydrogen bonds
      from four water molecules but does not act as a proton donor.

PMID- 10944327
TI  - Sarcosinium trifluoroacetate.
AB  - The title compound, C(3)H(8)NO(2)(+).C(2)F(3)O(2)(-), crystallizes in space group
      C2/c. The main N-C-COOH skeleton of the protonated sarcosine molecule is almost
      perfectly planar. The trifluoroacetate anion has a staggered conformation and
      typical bond distances and angles. The CF(3) group is probably slightly
      disordered. The structure is stabilized by an extensive network of strong O-H.O
      hydrogen bonds and weaker N-H.O bonds.

PMID- 10944328
TI  - (-)-(1R,2S,2'R,5R)-2-(1-Hydroxyprop-2-yl)-5-methylcyclohexanol. corrigendum
AB  - The crystal structure of the title compound, C(10)H(20)O(2), was published
      [Korner et al. (2000). Acta Cryst. C56, 74-75] with an erroneous position for an
      hydroxy H atom. This has now been corrected and leads to a more sensible hydrogen
      bonding scheme.

PMID- 10944329
TI  - Structure of the nucleotide-binding domain of Plasmodium falciparum rab6 in the
      GDP-bound form.
AB  - Rab proteins are small Ras-like GTPases which play important roles in regulating
      intracellular vesicle trafficking. The nucleotide-binding domain of Rab6 from the
      malaria parasite Plasmodium falciparum was crystallized with GDP bound to the
      active site. The MAD phasing technique was used to determine the crystal
      structure to 2.3 A resolution. Comparisons of the structure of GDP-bound PfRab6
      with the recently determined structures of Rab3A in complex with either a GTP
      analog or with GTP and Rabphillin present structural evidence supporting the
      traditional model for the molecular GTP/GDP switch in Rab proteins. PfRab6
      residues homologous to those distinguishing human Rab6 isoforms, which differ in
      binding to Rabkinesin-6 in human cells, are located next to the recognized
      complementarity-determining region (CDR) and constitute a conceptual broadening
      of that domain. Despite significant observable differences in Golgi
      ultrastructure, the Rab6 core structure and switch mechanism appear highly
      conserved when compared with murine Rab3a structures. A significant difference
      between the PfRab6 and higher eukaryotic Rabs may be the lack of CDR features
      that allow binding interactions with Rabkinesin-type effectors.

PMID- 10944330
TI  - Structure of the Fab fragment from F124, a monoclonal antibody specific for
      hepatitis B surface antigen.
AB  - The crystal structure of the Fab fragment from the monoclonal anti-preS2 antibody
      F124 (IgG1,kappa) has been solved by molecular replacement and refined at 3.0 A
      resolution. The Fab crystallizes with two independent molecules in the asymmetric
      unit. F124 recognizes an epitope contained within the preS2 segment between
      residues 120 and 132 of the surface antigen of hepatitis B virus. The antibody
      shows a high affinity for the glycan N-linked to Asn123, but it also cross-reacts
      with the non-glycosylated peptide fragment 120-132. Although crystallization was
      performed in the presence of an eightfold excess of the cross-reactive peptide,
      no evidence for the ligand was found in the antigen-binding site, which is close
      to a neighbouring molecule in the crystal lattice. The antigen-binding site has a
      groove-like topology which is modulated with pocket-like cavities. It is
      characterized by a large number of tyrosine and aspartate residues. The
      importance of germ-line mutations at the binding site is discussed.

PMID- 10944331
TI  - Crystallization, structure solution and refinement of hen egg-white lysozyme at
      pH 8.0 in the presence of MPD.
AB  - Hen egg-white lysozyme has been crystallized at slightly alkaline pH using 2
      methyl-2,4-pentanediol (MPD) as the precipitant. The crystals are nearly
      isomorphous to crystals grown at acidic pH using sodium chloride as the
      precipitant. However, the growth kinetics differ markedly between the two
      conditions. The major reason for this is a molecule of MPD that binds tightly in
      between two lysozyme molecules and favors the growth of the crystals along the
      crystallographic c direction over growth perpendicular to it.

PMID- 10944332
TI  - Effects of crystal twinning on the ability to solve a macromolecular structure
      using multiwavelength anomalous diffraction.
AB  - The crystal structure of gpD, the capsid-stabilizing protein of bacteriophage
      lambda, was solved by multiwavelength anomalous diffraction (MAD) for a
      selenomethionine (SeMet) derivative of the protein at 1.8 A resolution, using
      crystals in space group P2(1) [Yang et al. (2000), Nature Struct. Biol. 7, 230
      237]. Subsequent analysis showed that the crystals of both the original protein
      and the SeMet derivative were pseudo-merohedrally twinned with a twinning
      fraction approximately 0.36, owing to the near-identity of the a and c axes. An
      analysis of the crystal structure solution is presented and the utility of
      twinned crystals for solving the structure using MAD and of different phasing
      strategies is discussed; the results obtained with several software packages are
      compared.

PMID- 10944333
TI  - Maximum-likelihood density modification.
AB  - A likelihood-based approach to density modification is developed that can be
      applied to a wide variety of cases where some information about the electron
      density at various points in the unit cell is available. The key to the approach
      consists of developing likelihood functions that represent the probability that a
      particular value of electron density is consistent with prior expectations for
      the electron density at that point in the unit cell. These likelihood functions
      are then combined with likelihood functions based on experimental observations
      and with others containing any prior knowledge about structure factors to form a
      combined likelihood function for each structure factor. A simple and general
      approach to maximizing the combined likelihood function is developed. It is found
      that this likelihood-based approach yields greater phase improvement in model and
      real test cases than either conventional solvent flattening and histogram
      matching or a recent reciprocal-space solvent-flattening procedure [Terwilliger
      (1999), Acta Cryst. D55, 1863-1871].

PMID- 10944334
TI  - Towards automated Laue data processing: application to the choice of optimal X
      ray spectrum.
AB  - Laue data reduction has now reached a level of sophistication that allows nearly
      automated processing to be performed. The software described enables complete
      reduction of the data with essentially no user intervention, making Laue
      processing almost as straightforward as monochromatic data processing.
      Interactive work is limited to the indexing of only one Laue pattern. More
      importantly, it is shown that the data quality is substantially enhanced when
      soft-limited predictions are used. Further improvement obtained by taking
      advantage of the structure-factor amplitudes from a known closely related
      structure is described. To determine the most suitable type of insertion device
      to be used for time-resolved Laue crystallography, the technique described was
      applied to Laue data sets collected from photoactive yellow protein under
      identical conditions but with three different insertion devices: a wiggler, a
      broad-bandpass undulator and a single-line undulator. Although the optimal choice
      may ultimately be dictated by sample parameters (such as mosaic spread) and by
      the type of experiment (repeatable or non-repeatable reactions), the results here
      show that the use of single-line undulators will generally yield by far the best
      compromise between data quality, acquisition time and radiation damage.

PMID- 10944335
TI  - The high-mosaicity illusion: revealing the true physical characteristics of
      macromolecular crystals.
AB  - Typical measurements of macromolecular crystal mosaicity are dominated by the
      characteristics of the X-ray beam and as a result the mosaicity value given
      during data processing can be an artifact of the instrumentation rather than the
      sample. For physical characterization of crystals, an experimental system and
      software have been developed to simultaneously measure the diffraction resolution
      and mosaic spread of macromolecular crystals. The contributions of the X-ray beam
      to the reflection angular widths were minimized by using a highly parallel,
      highly monochromatic synchrotron source. Hundreds of reflection profiles over a
      wide resolution range were rapidly measured using a charge-coupled device (CCD)
      area detector in combination with superfine phi-slicing data collection. The
      Lorentz effect and beam contributions were evaluated and deconvoluted from the
      recorded data. Data collection and processing is described. From 1 degrees of
      superfine phi-slice data collected on a crystal of manganese superoxide
      dismutase, the mosaicities of 260 reflections were measured. The average
      mosaicity was 0.0101 degrees (s.d. 0.0035 degrees ) measured as the full-width at
      half-maximum (FWHM) and ranged from 0.0011 to 0. 0188 degrees. Each reflection
      profile was individually fitted with two Gaussian profiles, with the first
      Gaussian contributing 55% (s.d. 9%) and the second contributing 35% (s.d. 9%) of
      the reflection. On average, the deconvoluted width of the first Gaussian was
      0.0054 degrees (s.d. 0.0015 degrees ) and the second was 0.0061 degrees (s. d.
      0.0023 degrees ). The mosaicity of the crystal was anisotropic, with FWHM values
      of 0.0068, 0.0140 and 0.0046 degrees along the a, b and c axes, respectively. The
      anisotropic mosaicity analysis indicates that the crystal is most perfect in the
      direction that corresponds to the favored growth direction of the crystal.

PMID- 10944336
TI  - Cryosalts: suppression of ice formation in macromolecular crystallography.
AB  - Quality data collection for macromolecular cryocrystallography requires
      suppressing the formation of crystalline or microcrystalline ice that may result
      from flash-freezing crystals. Described here is the use of lithium formate,
      lithium chloride and other highly soluble salts for forming ice-ring-free aqueous
      glasses upon cooling from ambient temperature to 100 K. These cryosalts are a new
      class of cryoprotectants that are shown to be effective with a variety of
      commonly used crystallization solutions and with proteins crystallized under
      different conditions. The influence of cryosalts on crystal mosaicity and
      diffraction resolution is comparable with or superior to traditional organic
      cryoprotectants.

PMID- 10944337
TI  - Implementation of cluster analysis for ab initio phasing using the molecular
      envelope from solution X-ray scattering.
AB  - Solution of the phase problem is central to crystallographic structure
      determination. The conventional methods of isomorphous replacement (MIR or SIR)
      and molecular replacement are ineffective in the absence of a suitable
      isomorphous heavy-atom derivative or knowledge of the structure of a homologous
      protein. A recent method utilizing the low-resolution molecular shape determined
      from solution X-ray scattering data has shown to be successful in locating the
      molecular shape within the crystallographic unit cell in the case of the trimer
      nitrite reductase (NiR, 105 kDa) [Hao et al. (1999), Acta Cryst. D55, 243-246].
      This was achieved by performing a direct real-space search for orientation and
      translation using knowledge of the orientation of the polar angles of the non
      crystallographic axis obtained by performing a self-rotation on crystallographic
      data. This effectively reduces the potential six-dimensional search to a four
      dimensional one (Eulerian angle gamma and three translational parameters). In the
      case of NiR, the direct four-dimensional search produced a clear solution that
      was in good agreement with the known structure. The program FSEARCH incorporating
      this method has been generalized to handle molecules from all space groups and in
      particular those in possession of non-crystallographic symmetry. However, the
      method employed was initially unsuccessful when applied to the small dimeric
      molecule superoxide dismutase (SOD, 32 kDa) owing to the absence of strong
      reflections at low resolution caused by saturation at the detector. The
      determined solution deviated greatly from that of the known structure [Hough &
      Hasnain (1999), J. Mol. Biol. 287, 579-592]. It was found that once these absent
      reflections were replaced by a series of randomly generated intensity values and
      cluster analysis was performed on the output, the signal-to-noise ratio was
      improved and a most probable solution was found. The electron-density map of the
      stochastically determined solution agrees well with the known structure; the
      phase error calculated from this map was 67 degrees within 14 A resolution.

PMID- 10944338
TI  - Crystallization and molecular-replacement studies of a recombinant antigen
      binding fragment complexed with single-stranded DNA.
AB  - Anti-DNA antibodies have been implicated in autoimmune diseases and also serve as
      models for understanding protein-DNA recognition. Crystals of a recombinant
      antigen-binding fragment (Fab) complexed with dT(5) have been obtained and
      initial phases have been determined using molecular replacement. The crystals
      diffract to 2.1 A resolution and occupy space group P6(5)22, with unit-cell
      parameters a = 171.8, c = 144.6 A; there are two Fabs per asymmetric unit. X
      PLORdirect rotation-function calculations followed by Patterson correlation
      filtering were successful when using a Fab search model; however, they failed
      when using the individual variable and conserved domains of the Fab as search
      models. AMoRe successfully identified the correct solution in cases where X-PLOR
      failed.

PMID- 10944339
TI  - Crystallization and preliminary X-ray analyses of insect neurotoxins with
      analgesic effect from the scorpion Buthus martensii Karsch.
AB  - Three insect neurotoxins from the scorpion Buthus martensii Karsch, named BmK I1,
      BmK I4 and BmK I6, have been purified and crystallized. BmK I1 and BmK I4 show
      strong toxicity to insects, while BmK I6 is relatively weaker. They all exhibit
      an evident analgesic effect on mice; this is a novel biological function for
      scorpion insect toxins. Their crystals diffract to at least 3.5 (BmK I1), 2.8
      (BmK I4), 2.8 (BmK I6 crystal form I) and 2.2 A (of BmK I6 crystal form II)
      resolution on an ordinary X-ray source. Crystals of BmK I1 belong to space group
      P6, with unit-cell parameters a = b = 66.2, c = 176.7 A. BmK I4 crystallized in
      the tetragonal space group I4, with unit-cell parameters a = b = 134.5, c = 60.6
      A. BmK I6 has been crystallized in two forms: form I belongs to space group C2,
      with unit-cell parameters a = 46.5, b = 85.2, c = 32.6 A, beta = 110.5 degrees;
      form II belongs to space group R3, with the hexagonal unit-cell parameters a = b
      = 44.5, c = 164.7 A.

PMID- 10944340
TI  - Crystallization and diffraction to ultrahigh resolution (0.8 A) of a designed
      variant of the Rop protein.
AB  - The Rop protein is the paradigm of a highly regular four-alpha-helix bundle and
      as such has been subject to numerous structural and mutagenesis studies. Crystals
      of a designed Rop variant which establishes a continuous heptad pattern through
      the bend region have been obtained by a combination of vapour-diffusion and
      seeding techniques. The crystals diffract to ultrahigh (0.8 A) resolution using
      synchrotron radiation and cryogenic conditions.

PMID- 10944342
TI  - Crystallization and X-ray diffraction analysis of peroxisomal Delta3-Delta2-enoyl
      CoA isomerase from Saccharomyces cerevisiae.
AB  - The purification, crystallization and X-ray diffraction analysis of Saccharomyces
      cerevisiae Delta(3)-Delta(2)-enoyl-CoA isomerase is described. Delta(3)-Delta(2)
      Enoyl-CoA isomerase is a member of the hydratase/isomerase protein family and is
      an auxiliary enzyme required for the beta-oxidation of unsaturated fatty acids.
      It is a hexameric enzyme consisting of six identical 32 kDa subunits of 280
      residues each. In crystallization trials three crystal forms were obtained, with
      tetragonal and hexagonal lattices. A 2.5 A data set was collected from the
      unliganded hexagonal crystals with an R(merge) of 6.6%. The crystal, with unit
      cell parameters a = 116.0, b = 116.0, c = 122.9 A, is likely to have P6(3)22
      symmetry.

PMID- 10944341
TI  - Plasmodium falciparum rab6 GTPase: expression, purification, crystallization and
      preliminary crystallographic studies.
AB  - The Plasmodium falciparum rab6 gene encodes a 208 amino-acid polypeptide. Two
      recombinant versions of P. falciparum Rab6 protein were expressed in Escherichia
      coli: the full-length protein and a truncated form containing residues 1-175.
      Both forms were purified from the soluble fraction of bacterial extract and were
      purified by ion-exchange chromatography and size-exclusion chromatography.
      Purified proteins were crystallized at pH 6.5 using the hanging-drop vapor
      diffusion technique at room temperature. The full-length protein diffracted to
      2.4 A and belongs to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2, with
      unit-cell parameters a = b = 80. 6, c = 90.4 A. The crystals of the truncated
      protein were isomorphous with those of the full-length construct and diffracted X
      rays to 2.2 A resolution.

PMID- 10944343
TI  - Crystallization and preliminary X-ray analysis of Clostridium botulinum
      neurotoxin type B.
AB  - Single crystals of Clostridium botulinum neurotoxin type B have been obtained by
      the vapor-diffusion method. These crystals belong to space group P2(1), with unit
      cell parameters a = 76.08, b = 123.11, c = 95.86 A, beta = 113.03 degrees and
      diffract to at least 1.8 A resolution. Native data have been collected from flash
      frozen crystals at the National Synchrotron facility of Brookhaven National
      Laboratory. These crystals often tend to be non-isomorphic.

PMID- 10944344
TI  - Crystallization and preliminary X-ray analysis of the Clostridium thermocellum
      cellulosome xylanase Z feruloyl esterase domain.
AB  - Feruloyl esterases cleave ferulic acid from arabinoxylan and pectin. Feruloyl
      groups are believed to crosslink the polysaccharide chain within the polymer and
      to link hemicellulose to lignin, which may play a role in controlling the growth
      of plants. The Clostridium thermocellum cellulosome xylanase Z feruloyl esterase
      was expressed in Escherichia coli, purified and crystallized. The crystals
      diffract to 2.4 A resolution and belong to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 43.14, b = 63.77, c = 79.57 A.
      Assuming one molecule per asymmetric unit, the Matthews coefficient is calculated
      to be 1.87 A(3) Da(-1), which corresponds to a solvent content of 34%.

PMID- 10944345
TI  - Crystallization and preliminary X-ray diffraction studies of the signal
      recognition particle receptor FtsY from Mycoplasma mycoides.
AB  - The prokaryotic signal recognition particle (SRP) pathway comprises two proteins,
      Ffh and FtsY, homologous to the SRP54 and SRalpha proteins in the more complex
      eukaryotic system. All four proteins are part of a unique subfamily of GTPases.
      Four truncated versions of the 412 amino-acid FtsY receptor protein from
      Mycoplasma mycoides have been cloned, expressed in Escherichia coli and purified.
      Purified proteins from all constructs and the full-length FtsY protein were
      subjected to crystallization trials. Crystals were obtained for the construct
      which comprised residues 98-412 corresponding to the conserved NG-domain
      (residues 194-497 in E. coli). A native data set at 1.9 A resolution has been
      collected at 100 K using synchrotron radiation. The crystals belong to the space
      group P2(1)2(1)2, with unit-cell parameters a = 68.7, b = 101.1, c = 42.5 A and
      one molecule in the asymmetric unit.

PMID- 10944346
TI  - Crystallization and preliminary X-ray analysis of the conserved domain IV of
      Escherichia coli 4.5S RNA.
AB  - 4.5S RNA forms with Ffh protein the prokaryotic signal recognition particle
      (SRP), a highly conserved ribonucleoprotein complex essential for protein
      secretion. It also independently binds to elongation factor G (EF-G) in the
      ribosome and has a function in a subset of translocation events that is transient
      but required for viability. Crystals of three different constructs encompassing
      the conserved domain IV of 4.5S RNA, containing the recognition elements for both
      Ffh and EF-G, were obtained. Native X-ray diffraction data were collected for two
      crystal forms under cryogenic cooling conditions. The best crystals are of a 45
      nt construct, diffract anisotropically to 2.6 A resolution using synchrotron
      radiation and belong to space group P3(2)21, with unit-cell parameters a = b =
      69.1, c = 84.6 A and a single RNA molecule per asymmetric unit.

PMID- 10944347
TI  - A crystallizable form of RIIbeta regulatory domain obtained by limited
      proteolysis.
AB  - The type RIIbeta regulatory subunit of protein kinase A is primarily expressed in
      adipose tissue and brain. Knockout mice suggest a role for RIIbeta in regulating
      energy balance and adipose-tissue content, thus making it a potential target for
      therapeutic intervention in obesity. A truncated version of the RIalpha subunit
      has been used in a crystallographic study and was used here to design an
      analogous RIIbeta construct. Despite substantial screening, conditions were not
      found for the crystallization of the truncated RIIbeta subunit. However, limited
      proteolysis of the full-length RIIbeta subunit identified boundaries of the
      'hinge' region and a fragment containing the two cAMP-binding domains which did
      crystallize. A recombinant version of the fragment was expressed and crystallized
      for X-ray diffraction studies. The crystals belong to the orthorhombic space
      group C222, with unit-cell parameters a = 91.6, b = 105.9, c = 85.8 A, and
      diffracted to at least 2.3 A.

PMID- 10944348
TI  - Crystallization and preliminary crystallographic analysis of the Rho-binding
      domain of bovine Rho-kinase.
AB  - Rho-kinase binds to a small GTPase Rho in a GTP-dependent manner and regulates
      many cytoskeletal events in the cell. The minimum region of bovine Rho-kinase
      sufficient for Rho-binding was expressed as a fusion protein with glutathione S
      transferase. After removal of the glutathione S-transferase, thin plate crystals
      were obtained. The selenomethionine-substituted protein was introduced and
      crystallized, as was the native protein. The crystals of the Rho-binding domain
      of Rho-kinase belong to the space group C2, with unit-cell parameters a = 148.0
      (2), b = 26.1 (1), c = 39.6 (1) A, beta = 90.3 (1) degrees. The crystals diffract
      to a resolution beyond 1.5 A.

PMID- 10944349
TI  - Crystallization and preliminary X-ray crystallographic analysis of PdxJ, the
      pyridoxine 5'-phosphate synthesizing enzyme.
AB  - The enzyme PdxJ catalyzes the condensation of 1-deoxy-D-xylulose-5-phosphate
      (DXP) and 1-amino-3-oxo-4-(phosphohydroxy)propan-2-one to form pyridoxine 5'
      phosphate (PNP). The protein from Escherichia coli has been crystallized in
      several forms under different conditions. The best diffracting crystals were
      obtained by a combination of the hanging-drop vapour-diffusion and microseeding
      techniques. Using an in-house image plate, the PdxJ crystals diffracted under
      cryo-conditions to 2.6 A resolution. The space group has been determined as
      C222(1), with unit-cell parameters a = 132.5, b = 154. 4, c = 131.4 A,
      corresponding to four monomers per asymmetric unit. In the search for heavy-atom
      derivatives, a mercury derivative has been interpreted. The 12 mercury sites
      located are related by 222 symmetry and, in combination with self-rotation search
      analyses and gel-filtration experiments, indicate the quaternary assembly of PdxJ
      into octamers with 422 symmetry.

PMID- 10944350
TI  - Crystallization and preliminary X-ray crystallographic studies on
      maltosyltransferase from Thermotoga maritima.
AB  - Thermotoga maritima maltosyltransferase (MTase) is a 73.7 kDa molecular weight
      amylolytic enzyme which catalyzes the transfer of maltosyl units from
      maltodextrins or starch to suitable acceptors. Crystals of recombinant MTase have
      been obtained by the hanging-drop vapour-diffusion method using ammonium
      phosphate as a precipitating agent. The crystals belong to space group P4(1)22 or
      its enantiomorph P4(3)22, with unit-cell parameters a = b = 148.7, c = 106.7 A.
      The asymmetric unit appears to contain one subunit, corresponding to a very low
      packing density of 4.0 A(3) Da(-1). The crystals diffract X-rays to at least 2.4
      A resolution on a synchrotron-radiation source.

PMID- 10944351
TI  - Crystallization and preliminary crystallographic investigations of avian 5
      aminoimidazole-4-carboxamide ribonucleotide transformylase-inosine monophosphate
      cyclohydrolase expressed in Escherichia coli.
AB  - ATIC [5-aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR Tfase)
      inosine monophosphate cyclohydrolase (IMPCH)] is a bifunctional enzyme that
      catalyzes the penultimate and final steps in the de novo purine biosynthesis
      pathway and thus is an attractive anticancer target. Recombinant avian ATIC has
      been purified from an Escherichia coli expression system and crystallized in a
      binary complex with methotrexate (MTX). Crystals were obtained from PEG 4000 or
      MPEG 5000 buffered at pH 7.0-7.2 and data were collected from a single crystal at
      96 K to 2.3 A resolution at the Stanford Synchrotron Radiation Laboratory (SSRL).
      The crystals are monoclinic and belong to space group P2(1), with unit-cell
      dimensions a = 65.17, b = 105.93, c = 103.47 A, beta = 108.27 degrees. Assuming
      two molecules per asymmetric unit, the Matthews coefficient V(m) is 2.63 A(3) Da(
      1) and the solvent volume is 52.9%.

PMID- 10944352
TI  - Preliminary crystallographic study of turkey gizzard vinculin.
AB  - Vinculin is a 117 kDa microfilament-associated protein located at the cytoplasmic
      aspects of focal contacts and cell-cell adherens type junctions. In both sites,
      vinculin participates in the formation of a submembrane 'plaque' structure which
      is responsible for the attachment of actin filaments to the plasma membrane.
      Vinculin consists of 1066 amino acids, which form a large 90 kDa globular head
      domain and a rod-like 29 kDa tail domain. The two domains are separated by
      several stretches of proline residues where the major proteolytic cleavage sites
      are located. The experimental procedure for isolation and purification of
      vinculin from smooth muscle has been developed and crystals of native vinculin
      suitable for X-ray analysis have been obtained. The homogeneity of the vinculin
      solution was analyzed prior to crystallization using dynamic light scattering.
      Crystals of vinculin have been obtained in buffer containing 2 mg ml(-1) protein,
      0.9 M ammonium sulfate, 0.1 M MES pH 6.5 using both the hanging-drop and sitting
      drop vapour-diffusion methods. The crystals have the form of rhombic plates and
      grow to maximal dimensions of 0.3 x 0.3 x 0.05 mm in two weeks. Preliminary X-ray
      data show that the crystals diffract to 3.5 A resolution at the X11 beamline of
      DESY and belong to the monoclinic space group P2(1). Crystal unit-cell parameters
      are estimated to be a = 57, b = 351, c = 70 A, alpha = 90, beta = 113, gamma = 90
      degrees.

PMID- 10944353
TI  - Purification, crystallization and preliminary X-ray study of beta-xylosidase from
      Trichoderma reesei.
AB  - An extracellular multifunctional beta-xylosidase was purified from a culture of
      the fungus Trichoderma reesei. The active 95 +/- 5 kDa enzyme has been
      crystallized from sodium acetate buffer using PEG as a precipitant. The crystals
      belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a
      = 67.75, b = 98.54, c = 227.25 A, and diffract beyond 2.7 A resolution. X-ray
      data were collected from frozen crystals on a synchrotron source.

PMID- 10944354
TI  - Crystallization and structure determination of the catalytic trimer of
      Methanococcus jannaschii aspartate transcarbamoylase.
AB  - Aspartate transcarbamoylase (ATCase) catalyzes the first step in the pyrimidine
      biosynthetic pathway, the reaction between carbamoyl phosphate and L-aspartate to
      form N-carbamoyl-L-aspartate and phosphate. The structural analysis of the ATCase
      catalytic trimer from Methanococcus jannaschii, a unicellular thermophilic
      archaeabacterium, has been undertaken in order to gain insight into the
      structural features that are responsible for the thermostability of the enzyme.
      As a first step, the catalytic trimer was crystallized in space group R32, with
      unit-cell parameters a = b = 265.3, c = 195.5 A and two trimers in the asymmetric
      unit. Its structure was determined using molecular replacement and Patterson
      methods. In general, structures containing multiple copies of molecules in the
      asymmetric unit are difficult to determine. In this case, the two trimers in the
      asymmetric unit are parallel to each other and use of the Patterson function
      greatly simplified the structure solution.

PMID- 10944355
TI  - Apocrustacyanin A1 from the lobster carotenoprotein alpha-crustacyanin:
      crystallization and initial X-ray analysis involving softer X-rays.
AB  - The A1 subunit of the carotenoprotein alpha-crustacyanin, isolated from lobster
      carapace, has been crystallized using the vapour-diffusion method. The crystals,
      grown in solutions of ammonium sulfate containing methylpentanediol (MPD),
      diffracted to 2. 0 A. The crystals are stable to radiation. The space group of
      the crystals is P2(1)2(1)2(1). The unit-cell parameters are a = 41.9, b = 80.7, c
      = 110.8 A. 'Standard structure determination' has been unsuccessful within this
      crustacyanin family. Instead, an approach based on the S atoms is being
      undertaken involving softer X-rays at the SRS, Daresbury.

PMID- 10944356
TI  - A neutralizing antibody Fab-influenza haemagglutinin complex with an
      unprecedented 2:1 stoichiometry: characterization and crystallization.
AB  - The haemagglutinin HA is a trimer of identical subunits and is the more abundant
      viral surface glycoprotein of the influenza virus. It is the target of antibodies
      that neutralize viral infectivity. Antibodies that bind to HA with 3:1 and 1:1
      stoichiometries have been identified. Here, an antibody whose Fab binds to HA
      with an unprecedented 2:1 Fab:HA stoichiometry is characterized. The complex has
      been crystallized and synchrotron data to 3.5 A resolution have been collected.
      Molecular replacement confirms the stoichiometry of the complex.

PMID- 10944357
TI  - On the distribution of the bulk-solvent correction parameters.
AB  - The distribution of the bulk-solvent correction parameters (B(sol), k(sol)) (as
      determined with an exponential scaling algorithm based on Babinet's principle)
      for 219 crystal structures deposited in the Protein Data Bank is presented. The
      distribution shows that (i) the range of values observed is far wider than the
      usually cited parameter range, (ii) the observed k(sol) values do not correlate
      with their assumed physical meaning and (iii) the two parameters are not
      independent and a reasonable agreement with the experimental data can be obtained
      through the application of a simple exponential function. These findings are
      interpreted in terms of the inability of the currently used algorithms to
      uncouple the values of the two parameters during macromolecular refinement.

PMID- 10944358
TI  - Molecular-replacement studies of Trichosanthes kirilowii lectin 1: a structure
      belonging to the family of type 2 ribosome-inactivating proteins.
AB  - Trichosanthes kirilowii lectin 1 (TKL-1) isolated from the tuber of T. kirilowii
      consists of two chains, each with a molecular weight of about 30 kDa. It has
      immunological properties which are similar to some ribosome-inactivating proteins
      (RIPs). TKL-1 was crystallized in space group P2(1)2(1)2(1) and diffraction data
      were collected to 2.7 A resolution. The molecular-replacement method was applied
      to solve the structure, using different chains of ricin, abrin-a and
      trichosanthin as search models. A set of consistent solutions was further
      verified by R(omit) profile analysis. In addition, the spatial arrangement of the
      two chains of TKL-1 is identical to that of type 2 RIPs.

PMID- 10944359
TI  - Purification, crystallization and preliminary crystallographic studies of an
      integral membrane protein, cytochrome bo3 ubiquinol oxidase from Escherichia
      coli.
AB  - Cytochrome bo(3) ubiquinol oxidase has been successfully purified for
      crystallization. Single crystals of this integral membrane protein diffract X
      rays to 3.5 A resolution and belong to the orthorhombic space group C222(1). From
      the diffraction data, the unit-cell parameters were determined to be a = 91.3, b
      = 370.3, c = 232.4 A. The crystals have a solvent content of 59% and contain two
      molecules per asymmetric unit. A search model generated from the structures of
      cytochrome c oxidase from Paracoccus denitrificans and the extrinsic domain of
      cytochrome bo(3) ubiquinol oxidase from Escherichia coli was used for molecular
      replacement studies, resulting in a solution with sensible molecular packing.

PMID- 10944360
TI  - Enhancement in the perfection of orthorhombic lysozyme crystals grown in a high
      magnetic field (10 T).
AB  - Orthorhombic crystals of hen egg-white (HEW) lysozyme were grown in a homogeneous
      and static magnetic field of 10 T. All crystals grown at 10 T were oriented such
      that their crystallographic c axes were parallel to the magnetic field direction
      and showed a narrower average full-width at half-maximum (FWHM) of the rocking
      curve than those grown at 0 T. Rocking-width measurements were made at the BL-10A
      station at the Photon Factory, Tsukuba, Japan, using a high-resolution vertical
      type four-circle diffractometer. Crystal perfection was evaluated using the FWHM
      of the rocking curve; the effects of the magnetic field on the quality of the
      crystals were examined by comparison of the FWHM of seven crystals grown at 10
      and 0 T. The FWHMs of the reflections along the a, b and c axes decreased by
      23.5, 35.3 and 27.8%, respectively, and those of other general reflections
      decreased by 17.4-42.2% in the crystals grown at high magnetic field. These
      results clearly showed that a magnetic field of 10 T improved the crystal
      perfection of the orthorhombic lysozyme crystals. As a result, the maximum
      resolution of X-ray diffraction increased from 1.3 A at 0 T to 1.13 A at 10 T.
      The magnetic field also affected the dimensions of the unit cell, increments
      being 0.2% for the a and c axes and 0.1% for the b axis, respectively. These
      facts suggest that the application of a high magnetic field during
      crystallization might result in remarkable enhancements in the diffraction power
      of protein crystals having magnetic anisotropy.

PMID- 10944363
TI  - Medical abortion: public health and private lives.

PMID- 10944364
TI  - Medical abortion regimens: historical context and overview.
AB  - Medical abortion offers an important alternative to surgical abortion for women
      with early pregnancies who wish to avoid a surgical procedure. More than 3
      million women worldwide have had medical abortions in the past decade alone. The
      best-studied regimens include mifepristone orally followed 36 to 48 hours later
      by a prostaglandin analog administered either orally or intravaginally. Because
      of political and social restrictions related to mifepristone, however,
      researchers have investigated alternative regimens, most notably methotrexate and
      misoprostol. Mifepristone regimens are approximately 95% effective for abortion
      at </=49 days' gestation. Efficacy between 50 and 63 days' gestation varies
      according to the type and route of administration of the prostaglandin analog.
      Complete abortion rates among these later gestations are clinically acceptable
      when mifepristone is followed by intravaginally administered misoprostol or
      gemeprost. This report reviews the development, efficacy, and side effects of
      mifepristone regimens.

PMID- 10944365
TI  - Medical abortion in social context.
AB  - Early medical abortion regimens, especially those that include mifepristone, have
      the potential to reshape the landscape of abortion provision in the United
      States. Because medical abortion does not require surgical training, it may
      attract new providers of abortion services from a variety of specialties,
      including advanced practice clinicians. The diffusion of abortion services into
      myriad clinical and office-based settings may reduce the violence that has been
      associated with abortion provision. However, a number of factors may slow the
      spread of medical abortion, at least initially. These factors include the need
      for accurate means to date early pregnancies, the need to arrange backup surgical
      services for the small number of patients who require them, the obligation to
      conform to existing legal mandates governing surgical abortion, and possible
      difficulties negotiating appropriate malpractice coverage and reimbursement.
      Educational initiatives are needed to help clinicians to overcome these barriers
      and to actualize mifepristone's potential in women's health care.

PMID- 10944366
TI  - Medical abortion service delivery.
AB  - Medical abortion with mifepristone and methotrexate regimens may be offered in a
      variety of American medical practice settings. In this article the new provider
      will find information on all aspects of the patient care delivery system for
      medical abortion, including physical space requirements, staffing and training,
      patient flow, cost, security, marketing, and quality assurance. Because of the
      limited published data available regarding logistic issues surrounding abortion
      care, the information in this article derives largely from the experiences of
      providers who have established medical abortion practices in their offices or
      clinics. Its goals are to help make the initial start-up phase briefer and more
      rewarding for new providers, to offer helpful guidelines for incorporation of
      medical abortion into practice, and to encourage more practitioners to see the
      benefits of adding this option to their practices.

PMID- 10944367
TI  - Counseling for medical abortion.
AB  - Counseling and education are correlated with women's satisfaction with all
      abortion care. They often assume a larger role in medical abortion because the
      patient is a more active participant in the abortion process. This article aims
      to enhance the practitioner's expertise in providing the information and care
      necessary for women considering early abortion with medical regimens. It offers
      general counseling guidelines and several likely clinical scenarios regarding the
      decision-making process, the screening of patients, and the initial and follow-up
      visits. Through effective communication, practitioners can provide the
      information and support that patients need to complete the abortion process
      safely and can help to strengthen women's confidence in managing their
      reproductive health experiences.

PMID- 10944369
TI  - Abortion with mifepristone and misoprostol: regimens, efficacy, acceptability and
      future directions.
AB  - Mifepristone at a dose of 600 mg followed by 400 microg misoprostol orally has
      been used for early abortion by hundreds of thousands of women with success rates
      at </=49 days' gestation ranging from 92% to 97%. Newer regimens may prove
      simpler than this standard regimen and may serve a larger number of patients.
      Vaginal rather than oral administration of misoprostol may have advantages,
      including improvement in the efficacy of mifepristone regimens at >49 days'
      gestation. A lower mifepristone dose of 200 mg and in-home self-administration of
      misoprostol both appear safe and effective. Although most research protocols have
      used ultrasonography to confirm gestational age, the method can be provided
      safely without routine reliance on ultrasonography. Acceptability of the method
      to care providers and to patients has been high in all studies. The introduction
      of medical abortion into general medical practice in the United States will teach
      us much about the practical aspects of service provision.

PMID- 10944368
TI  - The roles of clinical assessment, human chorionic gonadotropin assays, and
      ultrasonography in medical abortion practice.
AB  - The clinical assessment of patients who request early medical abortion includes
      confirmation of the diagnosis of pregnancy and estimation of gestational age.
      Accurate gestational dating is essential, because the efficacies of medical
      abortion regimens decline as pregnancy advances. Whereas medical abortion
      researchers in the United States have relied on routine ultrasonography for
      gestational dating, abortion providers experienced with mifepristone and
      prostaglandin regimens outside the United States have reported high efficacy and
      safety primarily with clinical dating parameters. Diligent follow-up of patients
      allows clinicians to confirm that complete abortion has occurred without
      complications. In cases of uncertain outcome or suspected ectopic pregnancy,
      transvaginal ultrasonography and beta-human chorionic gonadotropin assays can
      assist in prompt diagnosis and management. As medical abortion with mifepristone
      and misoprostol becomes more prevalent in the United States, studies will be
      needed to further evaluate the effects of these modalities on medical abortion
      outcomes.

PMID- 10944370
TI  - Alternatives to mifepristone regimens for medical abortion.
AB  - Alternatives to regimens with mifepristone and a prostaglandin analog for medical
      abortion emerged because of the need for accessible, effective, and safe options
      in areas of the world where mifepristone was unavailable. Studies of oral or
      intramuscular methotrexate combined with misoprostol have demonstrated complete
      abortion rates in the same range as mifepristone regimens at </=49 days'
      gestation. The overall abortion process with methotrexate and misoprostol takes
      longer, however, with 20% to 30% of women requiring from 1 to 5 weeks for the
      abortion to occur. Multiple investigators have confirmed the safety, efficacy,
      and acceptability of various methotrexate and misoprostol regimens. Recent
      reports suggest that misoprostol alone may have similar efficacy, but with
      significantly higher rates of side effects. Randomized trials are needed to
      directly compare the clinical efficacies and acceptabilities of available medical
      abortion regimens.

PMID- 10944371
TI  - Management of side effects and complications in medical abortion.
AB  - Side effects are an expected part of medical abortion; some, such as pain and
      bleeding, result from the abortion process itself and are generally managed with
      orally administered analgesics and counseling. True medication side effects most
      commonly include nausea, vomiting, diarrhea, and warmth or chills. Complications
      of medical abortion usually represent an extreme or severe side effect. Large
      series have reported transfusion rates of <1%. Because of the infrequency of
      uterine instrumentation, postabortal endometritis appears to be rare with medical
      abortion. As with early surgical abortion, the clinician must remain aware of the
      possibility for ectopic pregnancy. Overall approximately 2% to 10% of patients
      will require surgical intervention for control of bleeding, resolution of
      incomplete expulsion, or termination of a continuing pregnancy. Understanding the
      types of side effects and complications that can occur will enable the clinician
      to counsel patients properly as well as to understand when medical intervention
      is necessary during the medical abortion process.

PMID- 10944372
TI  - Early surgical abortion: an alternative to and backup for medical abortion.
AB  - Surgical abortion by vacuum aspiration is one of the most commonly reported
      surgical procedures in the United States. The developments of highly sensitive
      urinary pregnancy tests and transvaginal ultrasonography have encouraged the
      application of surgical abortion methods at earlier gestational ages. Manual
      vacuum aspiration with a handheld syringe safely accomplishes early abortion in a
      variety of settings, from elective abortion in the office or clinic setting to
      emergency care of a patient with an incomplete abortion. As a wider range of
      clinicians expresses interest in offering medical abortion, the appropriate use
      and technique of surgical backup are crucial in safely providing medical
      abortion. This article reviews vacuum aspiration during the first few weeks of
      pregnancy, with special attention to manual vacuum aspiration, both for elective
      surgical abortion and when intervention is required after medical abortion.

PMID- 10944373
TI  - Legal issues in the provision of medical abortion.
AB  - As early medical abortion becomes more widespread in the United States, those who
      wish to provide it need to understand how existing abortion restrictions apply to
      this procedure. Although these laws were written with a primary regard for
      surgical procedures, most will be broadly applicable to the provision of medical
      abortion as well. In this article we briefly describe common abortion
      regulations, including physician-only laws, reporting requirements, targeted
      regulation of abortion providers, "informed consent" laws with mandatory waiting
      periods, parental involvement requirements, and laws governing treatment of fetal
      tissue. We discuss the applicability of such requirements to medical abortions
      and describe how providers of medical abortion can comply. Finally, we address
      potential legislative and regulatory changes that could help to make medical
      abortion more widely accessible to women in the United States.

PMID- 10944374
TI  - Determination of erythromycin and related substances in enteric-coated tablet
      formulations by reversed-phase liquid chromatography.
AB  - An isocratic method for the identification and quantitation of erythromycin and
      related substances in enteric-coated tablet formulations using high-performance
      liquid chromatography (HPLC) with ultraviolet (UV) detection at 205 nm is
      described. A novel method for sample preparation using a molecular weight
      centrifuge filter to reduce the interferences observed from polymeric tablet
      coating material is also presented. Erythromycin HPLC assays are best run at high
      pH; therefore, various polymer columns were evaluated. The resulting HPLC method
      that was developed has several advantages over current pharmacopeial assay
      methods for enteric-coated erythromycin tablets. Comparative data from both
      methods for the same batch of EryTab tablets are presented. The method can also
      be applied to various other erythromycin formulations, including particle-coated
      tablets, erythromycin stearate tablets, and erythromycin ethylsuccinate
      suspensions and fermentation broths. A C18 Polymeric column is used with a mobile
      phase composition of 0.02 M potassium phosphate dibasic buffer (pH 9):
      acetonitrile (60:40) and flow rate of 1 mL/min. This method is more sensitive,
      specific, and rugged than the pharmacopeial method.

PMID- 10944375
TI  - Drug penetration as studied by noninvasive methods: fourier transform infrared
      attenuated total reflection, fourier transform infrared, and ultraviolet
      photoacoustic spectroscopy.
AB  - The penetration of the drugs dithranol and methoxsalen from semisolid Vaseline
      formulation into an artificial dodecanol-collodion membrane was followed by three
      spectroscopic methods; they are, step-scan Fourier transform infrared (FTIR)
      photoacoustic spectroscopy (PAS) with phase modulation, FTIR-attenuated total
      reflection (FTIR-ATR), and ultraviolet (UV) PAS. The uptake of the drug in the
      membrane was quantified by monitoring the dependence of an appropriate drug band
      on the penetration time. The PAS experiments were carried out with various
      modulation frequencies for generating various sampling depths. Based on Fick's
      second law, the diffusion coefficient was derived by numerical fitting of the
      experimental data. It appears that the diffusion coefficient for the drug in the
      membrane depends on the distance. The comparative studies demonstrate that FTIR
      ATR is favored for permeation studies, whereas the PAS techniques are capable of
      providing the drug penetration profile in the membrane. Thus, extended
      experimental data are available for new insight into the penetration process.
      However, because of the photacoustic cells at hand, PAS is only suitable for in
      vitro studies.

PMID- 10944376
TI  - Radical scavenging properties of novel benzopyran derivatives, TA248 and TA276,
      and effects of the compounds on ischemic/reperfused myocardium in dogs.
AB  - Characteristics of novel benzopyran derivatives, TA248 and TA276, and their
      effects on myocardial contraction in ischemic/reperfused hearts in dogs were
      examined. TA248 and TA276 inhibited NADPH-dependent lipid peroxidation induced by
      Fe(3+) in the rat brain homogenate. Both compounds reduced *O(2-) produced by
      xanthine-xanthine oxidase system in a dose-dependent manner. TA276 scavenged.OH
      generated by Fenton reaction in a dose-dependent manner. TA248 also inhibited
      the.OH production, but the effect was neither complete nor dose dependent.
      Myocardial contraction was assessed as segment shortening of the left ventricular
      wall in pentobarbital-anesthetized open-chest dogs. The segment shortening was
      decreased by the left anterior descending coronary artery ligation (ischemia) and
      returned by release of the ligated artery (reperfusion). The segment shortening
      did not recover fully during reperfusion. Either TA248 or TA276 injected 10 min
      before ischemia improved the recovery of myocardial contraction during
      reperfusion. Both compounds preserved the level of ATP in the 60-min reperfused
      myocardium. However, the level of lipid peroxides was not changed by TA248 and
      TA276. TA248 and TA276 may protect myocardium against ischemic/reperfusion
      insult, partly because of their free radical scavenging activity, but no
      significant change in myocardial lipid peroxide level was observed.

PMID- 10944377
TI  - Modeling the kinetics of release of octreotide from long-acting formulations
      injected intramuscularly in rabbits.
AB  - Long-acting repeatable formulations (LAR) based on polymeric microspheres were
      manufactured to deliver octreotide, an octapeptide analogue used in acromegaly.
      We developed a model to describe the complex triphasic concentration versus time
      profile observed in rabbits after intramuscular (i.m.) injection of these LAR
      formulations. A 5-mg x kg(-1) dose of octreotide in a reference LAR formulation
      was given im to eight rabbits; two groups of four rabbits each received a
      different formulation. In each animal, 26 blood samples were taken over 49 days.
      Concentrations of octreotide were assayed by radioimmunoassay. A model describing
      the concentration profile was developed. Octreotide release was described using
      the succession of an exponential model, a semiempirical non-Fickian model, and a
      delayed Weibull model. Parameters were estimated using nonlinear regression,
      first for the eight rabbits that received the reference formulation and then for
      the other eight animals. The model provides an adequate description of the
      concentration versus time profile for the three formulations. For the reference
      phase, erosion accounted for 87% of total drug release. The formulation
      encapsulating an octreotide-acetate complex showed a prolonged diffusion phase.

PMID- 10944378
TI  - Interfacial properties of barium sulfate suspensions. Implications in their
      stability.
AB  - A surface characterization of barium sulfate particles in aqueous suspensions was
      carried out in this work. With the aim of predicting the stability conditions of
      these widely used suspensions, the electrical surface properties of the particles
      were first studied by electrophoretic mobility determinations. It was found that
      both H(+) and OH(-) ions can be considered as potential-determining ions for the
      barium sulfate/water interface. The same conclusion was reached concerning the
      lattice ions, Ba(2+) (mainly) and SO(4)(2-). It was also found that increasing
      the concentration of sodium chloride in the dispersion medium can even change the
      sign of the zeta (zeta) potential: it is suggested that this behavior is an
      indirect effect provoked by changes in the solubility of barium sulfate with the
      ionic strength. To compute the van der Waals (LW) attraction between the
      particles as well as the acid-base contribution to the total energy of
      interaction, a thermodynamic characterization of the interface was also carried
      out by measuring the rate of penetration of selected liquids through plugs of the
      particles. It was found that barium sulfate particles are essentially monopolar
      in nature; that is, they show electron-donor character as demonstrated by the
      essentially zero value of the electron-acceptor component of their surface free
      energy. Pretreatment of the particles with 10(-2) M solutions of BaCl2 and CaCl2
      significantly reduced the electron-donor component, whereas both NaCl and
      Na(2)SO(4) provoked the opposite effect. This result is explained in terms of the
      acid-base character of the ions added. These data were used to calculate the
      interaction energy between the particles. The effect of electrolyte concentration
      on the stability of the suspensions was analyzed on the basis of the dependence
      with distance of the interaction energy between the particles. Our results
      suggest that more stable suspensions of barium sulfate are predicted if moderate
      amounts of SO(4)(2-) ions are added to the dispersion medium.

PMID- 10944379
TI  - Comparative kinetics of metabolism of beclomethasone propionate esters in human
      lung homogenates and plasma.
AB  - The systemic availability of inhaled beclomethasone dipropionate (BDP) is the net
      result of the absorption of the glucocorticoid from the lower respiratory and
      gastrointestinal tracts, and metabolism in the lung, plasma, and other sites. The
      metabolism kinetics of BDP and its active metabolite, beclomethasone 17
      monopropionate (17-BMP), in human lung 1000 x g supernatant (HLu) and human
      plasma (HP) at 37 degrees C were compared. The effect of MgCl(2) and/or an NADPH
      generating system on the decomposition of BDP and 17-BMP in HLu was also
      investigated. The concentrations of BDP and its metabolites were determined by
      HPLC with UV detection at 242 nm. Kinetics of decomposition of BDP and 17-BMP in
      HLu and HP were qualitatively and quantitatively different. The decomposition of
      BDP in HLu involved only hydrolysis. In comparison, three reactions are involved
      following incubation of BDP in HP; namely, hydrolysis, transesterification, and
      loss of hydrogen chloride. The hydrolysis of BDP and 17-BMP in HLu seem to be
      inhibited appreciably by MgCl(2) with the NADPH-generating system. Effective
      activation of BDP in HLu, in combination with transesterification of 17-BMP in
      HP, might favor a high ratio of local antiinflammatory activity to systemic side
      effects following inhalation of BDP.

PMID- 10944380
TI  - Polymorphism of tedisamil dihydrochloride.
AB  - The results of studies on tedisamil dihydrochloride in the solid state
      demonstrate that the compound occurs in three polymorphic forms. The three
      modifications have been characterized by thermomicroscopy, differential scanning
      calorimetry (DSC), vibrational spectroscopy, solid-state nuclear magnetic
      resonance (NMR), and X-ray powder diffractometry (XRPD). The thermodynamic
      relationships are illustrated in a semischematic energy/temperature diagram that
      gives information about the relative stability and physical properties of the
      three modifications between 0 K and the melting temperatures. The three
      modifications are enantiotropically related. Modification II, the material
      obtained during manufacturing, is the thermodynamically stable crystal form at 20
      degrees C. The thermodynamic transition point of mod II with I (instant melting
      point: 248-250 degrees C) is between 100 and approximately 140 degrees C
      (DeltaH(t,II/I) = 4.4+/-0.8 kJ/mol (95% CI)). A phase transition of mod II
      (probably into mod III) was detected thermomicroscopically at about -180 degrees
      C. The thermodynamic transition point of mod III with I was determined to be at 
      9 to -6 degrees C. Because mods I and III are thermodynamically and kinetically
      unstable at ambient conditions, these crystal forms are of analytical interest.

PMID- 10944381
TI  - Physicochemical factors governing the performance of nedocromil sodium as a dry
      powder aerosol.
AB  - Previous investigations have found that the in vitro aerosol performance of
      nedocromil sodium is poor. A study has been undertaken to gain a better
      understanding of the physicochemical properties of the drug particles together
      with the factors governing the aerosol performance of inhalation systems
      containing this drug. Material previously passed through a hammer mill only and
      particles subsequently passed through a micronizer were characterized, and the
      information gathered was correlated with the in vitro aerosol performance of the
      pure drug systems. Optimization of particle sizing procedures revealed that both
      sets of materials were ultrafine powders with a volume median diameter of
      approximately 1 microm. It is concluded that the processing stages, employed in
      the manufacture of these batches of fine particle nedocromil sodium trihydrate,
      may not in fact be primary particle size reduction stages but instead
      deaggregation stages and that these govern the aerosol performance. The in vitro
      aerosol performance of samples of the "micronized" nedocromil sodium stored over
      a range of relative humidities (RHs) was characterized. Storage RHs in the range
      12-76% (where nedocromil sodium is stable as the trihydrate) did not have a
      dramatic effect on the in vitro aerosol performance of the drug. However,
      conversion to the heptahemihydrate (following storage of the drug at 86% RH)
      significantly decreased the deaggregation performance in an in vitro model.

PMID- 10944383
TI  - Quantitative real-time monitoring of dryer effluent using fiber optic near
      infrared spectroscopy.
AB  - This paper describes a method for real-time quantitation of the solvents
      evaporating from a dryer. The vapor stream in the vacuum line of a dryer was
      monitored in real time using a fiber optic-coupled acousto-optic tunable filter
      near-infrared (AOTF-NIR) spectrometer. A balance was placed in the dryer, and
      mass readings were recorded for every scan of the AOTF-NIR. A partial least
      squares (PLS) calibration was subsequently built based on change in mass over
      change in time for solvents typically used in a chemical manufacturing plant.
      Controlling software for the AOTF-NIR was developed. The software collects
      spectra, builds the PLS calibration model, and continuously fits subsequently
      collected spectra to the calibration, allowing the operator to follow the mass
      loss of solvent from the dryer. The results indicate that solvent loss can be
      monitored and quantitated in real time using NIR for the optimization of drying
      times. These time-based mass loss values have also been used to calculate
      "dynamic" vapor density values for the solvents. The values calculated are in
      agreement with values determined from the ideal gas law and could prove valuable
      as tools to measure temperature or pressure indirectly.

PMID- 10944382
TI  - Transdermal extraction of interstitial fluid by low-frequency ultrasound
      quantified with 3H2O as a tracer molecule.
AB  - The transdermal extraction of interstitial fluid by low-frequency ultrasound
      offers a potential minimally invasive method of obtaining a fluid sample for at
      home blood glucose monitoring. Here we show that the application of low-frequency
      ultrasound (20 kHz) enhances the transdermal transport of interstitial fluid
      across hairless rat skin. Using 3H2O as a tracer injected intravenously, a
      measurable amount of water (>1 microL) was extracted without producing any
      histologic evidence of injury, even after repeated exposures. Piezoelectric
      transducers were imbedded in the extraction chamber and used to correlate
      ultrasound spectral properties to the amount of fluid extracted. Results indicate
      that the highest amount of water extracted occurs when the acoustic coupling
      media on the surface of the skin is cavitating, resulting in mild ablation of the
      stratum corneum and a reduction in its resistance to water mass transfer.

PMID- 10944384
TI  - The change of the rate-controlling processes with temperature in the hydration of
      anhydrous nedocromil sodium by water vapor.
AB  - A six-stage model is proposed to describe the overall process of sorption of
      water vapor on and into anhydrous nedocromil sodium. The way in which
      temperature, pressure, and time affect the rate of reaction for each of the
      stages has been analyzed. Experimental data for the measured rates, where
      temperature, pressure, and time are variables, are compared with the predictions
      obtained from each of the six stages. The most useful comparator is a graphical
      representation of reduced time versus hydration rate. The theoretical equations
      presented as a shape analysis of the experimental curves show the process to have
      different controlling mechanisms in three temperature regions: up to 27 degrees
      C, hydration is controlled by a nucleation and growth mechanism; between 27 and
      31 degrees C, the process is dominated by diffusion of water molecules into the
      crystal; and >31 degrees C, neither nucleation nor diffusion are controlling but
      some, as yet, undetermined physical processes.

PMID- 10944385
TI  - Dissolution kinetics of three-component compressed solid mixtures with largely
      different solubilities: flaking spheres.
AB  - The dissolution kinetics of three-component compressed solid spheres of various
      compositions of mannitol (MAN), sulfamethoxazole (SMX), and trimethoprim (TMP)
      were studied. Because the solubility of MAN was approximately 300 times that of
      SMX and TMP, the flaking phenomenon during dissolution process was observed. The
      critical flaking line was drawn between two critical flaking points in the
      triangular composition diagram of MAN-SMX-TMP mixtures (i.e., the compositions of
      0.5022 MAN and 0.4978 SMX mass fractions, and 0.4906 MAN and 0.5094 TMP mass
      fractions), thus dividing the system into two distinct regions; namely,
      nonflaking and flaking regions. In the case of nonflaking region, only three
      dissolution behaviors for MAN-SMX-TMP three-component mixtures were proposed. The
      calculated dissolution rates of all components by using the multicomponent
      dissolution model previously proposed were found to satisfactorily approximate
      the observed values for both two- and three-component solid mixtures. In the case
      of flaking region, the observed dissolution rate of MAN was found to be the
      exponential function of the mass fraction ratio of either SMX or TMP to MAN for
      both two- and three-component mixtures. The slope of the semilogarithmic plot of
      the observed MAN dissolution rate versus the mass fraction ratio of either SMX or
      TMP to MAN was defined as retarding coefficients of SMX or TMP, r'(SMX) or
      r'(TMP), respectively. The erosion rate of either SMX or TMP was the product of
      mass fraction ratio of drug to MAN and the exponential function of such mass
      fraction ratio. The mathematical model was developed on the basis of simultaneous
      erosion followed by dissolution of eroded particles to predict the dissolution
      rate of each drug from MAN-SMX-TMP compressed solid spheres within the flaking
      region.

PMID- 10944386
TI  - Physiologically relevant two-compartment pharmacokinetic models for skin.
AB  - Pharmacokinetic (compartment) models for skin have been used to predict or
      analyze absorption of chemical into and through skin. For highly lipophilic
      chemicals, the stratum corneum (sc) and the viable epidermis (v.e.) both
      contribute a significant resistance to chemical penetration and thus, both should
      be included in the model. This paper describes two-compartment models that
      represent the sc and the ve separately by extending the procedures previously
      developed for one-compartment models. The two-compartment models described here
      were developed by matching characteristics of a two-membrane model of skin. These
      compartment models were compared with membrane representations of the s.c. and
      v.e. for several different dermal exposure scenarios. When valid, which it is for
      many chemical exposure scenarios, the two-compartment model developed using
      characteristic times of the membrane model (model B2) more closely represents the
      two-membrane model than the model developed with equilibrium conditions of the
      membrane model (model B1). When model B2 is invalid, then model B1 is
      recommended. Criteria are provided for choosing from the various one- or two
      compartment model options.

PMID- 10944387
TI  - Building-block approach for determining low-frequency normal modes of
      macromolecules.
AB  - Normal mode analysis of proteins of various sizes, ranging from 46 (crambin) up
      to 858 residues (dimeric citrate synthase) were performed, by using standard
      approaches, as well as a recently proposed method that rests on the hypothesis
      that low-frequency normal modes of proteins can be described as pure rigid-body
      motions of blocks of consecutive amino-acid residues. Such a hypothesis is
      strongly supported by our results, because we show that the latter method, named
      RTB, yields very accurate approximations for the low-frequency normal modes of
      all proteins considered. Moreover, the quality of the normal modes thus obtained
      depends very little on the way the polypeptidic chain is split into blocks.
      Noteworthy, with six amino-acids per block, the normal modes are almost as
      accurate as with a single amino-acid per block. In this case, for a protein of n
      residues and N atoms, the RTB method requires the diagonalization of an n x n
      matrix, whereas standard procedures require the diagonalization of a 3N x 3N
      matrix. Being a fast method, our approach can be useful for normal mode analyses
      of large systems, paving the way for further developments and applications in
      contexts for which the normal modes are needed frequently, as for example during
      molecular dynamics calculations.

PMID- 10944388
TI  - Crystal structure of bovine duodenase, a serine protease, with dual trypsin and
      chymotrypsin-like specificities.
AB  - The three-dimensional structure of duodenase, a serine protease from bovine
      duodenum mucosa, has been determined at 2.4A resolution. The enzyme, which has
      both trypsin-like and chymotrypsin-like activities, most closely resembles human
      cathepsin G with which it shares 57% sequence identity and similar specificity.
      The catalytic Ser195 in duodenase adopts the energetically favored conformation
      typical of serine proteinases and unlike the strained state typical of
      lipase/esterases. Of several waters in the active site of duodenase, the one
      associated with Ser214 is found in all serine proteinases and most
      lipase/esterases. The conservation of the Ser214 residue in serine proteinase,
      its presence in the active site, and participation in a hydrogen water network
      involving the catalytic triad (His57, Asp107, and Ser195) argues for its having
      an important role in the mechanism of action. It may be referred to as a fourth
      member of the catalytic triad. Duodenase is one of a growing family of enzymes
      that possesses trypsin-like and chymotrypsin-like activity. Not long ago, these
      activities were considered to be mutually exclusive. Computer modeling reveals
      that the S1 subsite of duodenase has structural features compatible with
      effective accommodation of P1 residues typical of trypsin (Arg/Lys) and
      chymotrypsin (Tyr/Phe) substrates. The determination of structural features
      associated with functional variation in the enzyme family may permit design of
      enzymes with a specific ratio of trypsin and chymotrypsin activities.

PMID- 10944389
TI  - Prediction of protein secondary structure at 80% accuracy.
AB  - Secondary structure prediction involving up to 800 neural network predictions has
      been developed, by use of novel methods such as output expansion and a unique
      balloting procedure. An overall performance of 77.2%-80.2% (77.9%-80.6% mean per
      chain) for three-state (helix, strand, coil) prediction was obtained when
      evaluated on a commonly used set of 126 protein chains. The method uses profiles
      made by position-specific scoring matrices as input, while at the output level it
      predicts on three consecutive residues simultaneously. The predictions arise from
      tenfold, cross validated training and testing of 1032 protein sequences, using a
      scheme with primary structure neural networks followed by structure filtering
      neural networks. With respect to blind prediction, this work is preliminary and
      awaits evaluation by CASP4.

PMID- 10944390
TI  - On the unfolding of alpha-lytic protease and the role of the pro region.
AB  - Molecular dynamics simulations of alpha-lytic protease (alphaLP) alone and
      complexed with its pro region (PRO) are performed to understand the origin of its
      high unfolding (and folding) barrier when it is alone and how the pro region
      lowers this barrier. At room temperature, alphaLP exhibits lower dynamic
      fluctuations than alpha-chymotrypsin. Simulation of PRO alone led to
      reorientation of its N terminal helix and collapse to a more compact state. A
      model for the uncleaved proenzyme was built and found to be stable in the time
      scale of the simulations. Energetic analysis suggests that the origin of strain
      in the uncleaved proenzyme compared with the cleaved complex is in the
      intramolecular backbone electrostatic interactions of the cleaved strand. In high
      temperature simulations, the interaction of the long beta hairpin of the enzyme
      with the C terminal beta sheet of PRO is among the most stable in the complex and
      a likely "nucleation site" for folding. In the course of unfolding, the C
      terminal tail of PRO is sometimes observed to intervene between the long hairpin
      and the aspartate loop of the enzyme, perhaps thereby lowering the energy barrier
      for separation of the two hairpins. Tighter interactions at the interface between
      the enzyme and its pro region are also occasionally observed, providing an
      additional mechanism for unfolding catalysis. Simulations of a mutant enzyme
      where the buried ion pair residues R102 and D142 were replaced by W and L,
      respectively, did not display any distinguishable behavior compared with the wild
      type.

PMID- 10944391
TI  - Specific interaction of cytosolic and mitochondrial glyoxalase II with acidic
      phospholipids in form of liposomes results in the inhibition of the cytosolic
      enzyme only.
AB  - Kinetics of cytosolic recombinant human glyoxalase II and bovine liver
      mitochondrial glyoxalase II were studied in the presence of liposomes made of
      different phospholipids (PLs). Neutral PLs such as egg phosphatidylcholine or
      dipalmitoylphosphatidylcholine did not affect the enzymatic activity of either
      enzymatic form. Liposomes made of dioleoyl phosphatidic acid or cardiolipin or
      phosphatidylserine also did not affect the enzymatic activity of mitochondrial
      glyoxalase II. Conversely, these negatively charged PLs exerted noncompetitive
      inhibition on cytosolic glyoxalase II only, dioleoyl phosphatidic acid and bovine
      brain phosphatidylserine exerting the highest and lowest inhibition,
      respectively. Binding studies, carried out by using a resonant mirror biosensor,
      revealed that liposomes made of negatively charged PLs interact specifically with
      both enzymatic forms of glyoxalase II, whereas interactions were not detected
      with neutral PLs. Once bound on glyoxalase II, negatively charged liposomes could
      not be removed by 3 M NaCl, suggesting that interactions between glyoxalase II
      and negatively charged PLs, besides ionic, may be also hydrophobic. These data
      suggest a possible role of negatively charged phospholipids in the regulation of
      level of lactoylglutathione in the cell. The data are also discussed in terms of
      a possible regulation of reduced glutathione supply to mitochondria.

PMID- 10944392
TI  - Distance-dependent, pair potential for protein folding: results from linear
      optimization.
AB  - The results of an optimization of a folding potential are reported. The complete
      energy function is modeled as a sum of pairwise interactions with a flexible
      functional form. The relevant distance between two amino acids (2 - 9 A) is
      divided into 13 intervals, and the energy of each interval is optimized
      independently. We show, in accord with a previous publication (Tobi et al.,
      Proteins 2000;40:71-85) that it is impossible to find a pair potential with the
      above flexible form that recognizes all native folds. Nevertheless, a potential
      that rates correctly a subset of the decoy structures was constructed and
      optimized. The resulting potential is compared with a distance-dependent
      statistical potential of Bahar and Jernigan. It is further tested against decoy
      structures that were created in the Levitt's group. On average, the new potential
      places native shapes lower in energy and provides higher Z scores than other
      potentials.

PMID- 10944393
TI  - Discriminating between homodimeric and monomeric proteins in the crystalline
      state.
AB  - Scores calculated from intermolecular contacts of proteins in the crystalline
      state are used to differentiate monomeric and homodimeric proteins, by
      classification into two categories separated by a cut-off score value. The
      generalized classification error is estimated by using bootstrap re-sampling on a
      nonredundant set of 172 water-soluble proteins whose prevalent quaternary state
      in solution is known to be either monomeric or homodimeric. A statistical
      potential, based on atom-pair frequencies across interfaces observed with
      homodimers, is found to yield an error rate of 12.5%. This indicates a small but
      significant improvement over the measure of solvent accessible surface area
      buried in the contact interface, which achieves an error rate of 15.4%. A further
      modification of the latter parameter relating the two most extensive contacts of
      the crystal results in an even lower error rate of 11.1%.

PMID- 10944394
TI  - Unfolding of hen egg lysozyme by molecular dynamics simulations at 300K: insight
      into the role of the interdomain interface.
AB  - We present the results of two 1.2 ns molecular dynamics (MD) unfolding
      simulations on hen egg lysozyme in water at 300K, performed using a new procedure
      called PEDC (Path Exploration With Distance Constraints). This procedure allows
      exploration of low energy structures as a function of increasing RMSD from the
      native structure, and offers especially the possibility of extensive exploration
      of the conformational space during the initial unfolding stages. The two
      independent MD simulations gave similar chronology of unfolding events:
      disruption of the active site, kinking of helix C, partial unfolding of the three
      stranded beta-sheet to a two-stranded sheet (during which the helices A, B, and D
      remain to a great extent native), and finally unfolding of the beta-domain and
      partial unfolding of the alpha-domain in which hydrophobic clusters persist. We
      show particularly that the loss of hydrophobic contacts between the beta-sheet
      turn residues Leu55 and Ile56 and the hydrobic patch of the alpha-domain
      destabilizes the beta-domain and leads to its unfolding, suggesting that the
      correct embedding of these residues in the alpha-beta interface may constitute
      the rate limiting step in folding. These results are in accord with experimental
      observations on the folding/unfolding behavior of hen egg lysozyme at room
      temperature. They would also explain the loss of stability and the tendency to
      aggregation observed for the mutant Leu55Thr, and the slow refolding kinetics
      observed in the analogous amyloidogenic variant of human lysozyme.

PMID- 10944395
TI  - Model-free analysis of a thermophilic Fe(7)S(8) protein compared with a
      mesophilic Fe(4)S(4) protein.
AB  - 15N T(1), T(2) and (1)H-(15)N NOE were measured for the thermophilic Fe(7)S(8)
      protein from Bacillus schlegelii and for the Fe(4)S(4) HiPIP protein from
      Chromatium vinosum, which is a mesophilic protein. The investigation was
      performed at 276, 300, and 330 K at 11.7 T for the former, whereas only the 298 K
      data at 14.1 T for the latter were acquired. The data were analyzed with the
      model-free protocol after correcting the measured parameters for the effect of
      paramagnetism, because both proteins are paramagnetic. Both thermophilic and
      mesophilic proteins are quite rigid, with an average value of the generalized
      order parameter S2at room temperature of 0.92 and 0.94 for Fe(7)S(8) and
      Fe(4)S(4) proteins, respectively. The analyzed nitrogens for the Fe(7)S(8)
      protein showed a significant decrease in S2with increasing temperature, and at
      the highest temperature >70% of the residues had an internal correlation time.
      This research shows that subnanosecond rigidity is not related to thermostability
      and provides an estimate of the effect of increasing temperature on this time
      scale.

PMID- 10944396
TI  - Accurate reconstruction of all-atom protein representations from side-chain-based
      low-resolution models.
AB  - A procedure for the reconstruction of all-atom protein structures from side-chain
      center-based low-resolution models is introduced and applied to a set of test
      proteins with high-resolution X-ray structures. The accuracy of the rebuilt all
      atom models is measured by root mean square deviations to the corresponding X-ray
      structures and percentages of correct chi(1) and chi(2) side-chain dihedrals. The
      benefit of including C(alpha) positions in the low-resolution model is examined,
      and the effect of lattice-based models on the reconstruction accuracy is
      discussed. Programs and scripts implementing the reconstruction procedure are
      made available through the NIH research resource for Multiscale Modeling Tools in
      Structural Biology (http://mmtsb.scripps.edu).

PMID- 10944397
TI  - Practical limits of function prediction.
AB  - The widening gap between known protein sequences and their functions has led to
      the practice of assigning a potential function to a protein on the basis of
      sequence similarity to proteins whose function has been experimentally
      investigated. We present here a critical view of the theoretical and practical
      bases for this approach. The results obtained by analyzing a significant number
      of true sequence similarities, derived directly from structural alignments, point
      to the complexity of function prediction. Different aspects of protein function,
      including (i) enzymatic function classification, (ii) functional annotations in
      the form of key words, (iii) classes of cellular function, and (iv) conservation
      of binding sites can only be reliably transferred between similar sequences to a
      modest degree. The reason for this difficulty is a combination of the unavoidable
      database inaccuracies and the plasticity of protein function. In addition,
      analysis of the relationship between sequence and functional descriptions defines
      an empirical limit for pairwise-based functional annotations, namely, the three
      first digits of the six numbers used as descriptors of protein folds in the FSSP
      database can be predicted at an average level as low as 7.5% sequence identity,
      two of the four EC digits at 15% identity, half of the SWISS-PROT key words
      related to protein function would require 20% identity, and the prediction of
      half of the residues in the binding site can be made at the 30% sequence identity
      level.

PMID- 10944398
TI  - Protein structure comparison using the markov transition model of evolution.
AB  - A number of automatic protein structure comparison methods have been proposed;
      however, their similarity score functions are often decided by the researchers'
      intuition and trial-and-error, and not by theoretical background. We propose a
      novel theory to evaluate protein structure similarity, which is based on the
      Markov transition model of evolution. Our similarity score between structures i
      and j is defined as log P(j --> i)/P(i), where P(j --> i) is the probability that
      structure j changes to structure i during the evolutionary process, and P(i) is
      the probability that structure i appears by chance. This is a reasonable
      definition of structure similarity, especially for finding evolutionarily related
      (homologous) similarity. The probability P(j --> i) is estimated by the Markov
      transition model, which is similar to the Dayhoff's substitution model between
      amino acids. To estimate the parameters of the model, homologous protein
      structure pairs are collected using sequence similarity, and the numbers of
      structure transitions within the pairs are counted. Next these numbers are
      transformed to a transition probability matrix of the Markov transition.
      Transition probabilities for longer time are obtained by multiplying the
      probability matrix by itself several times. In this study, we generated three
      types of structure similarity scores: an environment score, a residue-residue
      distance score, and a secondary structure elements (SSE) score. Using these
      scores, we developed the structure comparison program, Matras (MArkovian
      TRAnsition of protein Structure). It employs a hierarchical alignment algorithm,
      in which a rough alignment is first obtained by SSEs, and then is improved with
      more detailed functions. We attempted an all-versus-all comparison of the SCOP
      database, and evaluated its ability to recognize a superfamily relationship,
      which was manually assigned to be homologous in the SCOP database. A comparison
      with the FSSP database shows that our program can recognize more homologous
      similarity than FSSP. We also discuss the reliability of our method, by studying
      the disagreement between structural classifications by Matras and SCOP.

PMID- 10944399
TI  - Measured and calculated effects of mutations in bacteriophage T4 lysozyme on
      interactions in solution.
AB  - Understanding the molecular determinants of protein interactions in solution has
      fundamental implications for understanding protein solution thermodynamics and,
      hence, processes as diverse as separations performance and cellular self
      organization. Our earlier theoretical calculations indicate that the protein
      protein interactions are dominated by a small number of configurations in which
      highly complementary surface regions are apposed, rather than by the overall
      colloidal interactions. To examine this paradigm more explicitly, we investigated
      the effects of protein structural modifications on protein-protein interactions.
      Experimental measurements are presented of B(22)(') values of a set of mutants of
      Ser44 in bacteriophage T4 lysozyme. Effects are seen with both charged and
      uncharged substitutions. The results with the charged substitutions follow the
      expected trends, whereas those with the uncharged substitutions may be explained
      by the impact of the mutations on the local protein geometry, which directly
      affects the complementarity of protein interactions. These effects are also
      captured well by molecular calculations that account for the mutations. The
      interaction energetics between protein pairs could provide information on the
      propensity for adventitious interactions, which can have important implications
      for separations and for normal and pathological self-assembly. Thus, protein
      structural data implicit in genomic information, coupled with appropriate
      calculational and experimental tools, can ultimately provide insights into
      protein interactions in vivo and in bioprocessing.

PMID- 10944400
TI  - Structural modeling of a plant disease resistance gene product domain.
AB  - Dominant plant resistance genes are involved in the protection of plants against
      a wide variety of pathogens. Sequence analysis has revealed a variety of classes,
      often having domains in common. One commonly found region has come to be known as
      a putative nucleotide-binding site (NBS) due to the simple presence of sequence
      motifs. Until now, no experimental evidence has supported this idea. Here we
      suggest, as an alternative hypothesis, that part of this region is structurally
      homologous to the receiver domain common to many proteins of His-Asp
      phosphotransfer pathways. This conclusion is based on sequence analysis,
      threading experiments, and the construction of a molecular model of one domain
      that performs well against structure validation tools. The new hypothesis, in
      contrast to the NBS hypothesis, can explain the devastating effect of a Thr-->Ala
      mutation in a well-characterized resistance gene product. According to the new
      hypothesis, regions located N-terminal and C-terminal to the modeled portion,
      containing highly conserved sequence motifs, could form a separate domain.

PMID- 10944402
TI  - Addendum to crystal structure of recombinant trypsin-solubilized fragment of
      cytochrome b(5) and the structural comparison with Val61His mutant

PMID- 10944401
TI  - Secretion of cytoplasmic and nuclear proteins from animal cells using novel
      secretion modules.
AB  - Production of recombinant proteins that are not secreted outside the producing
      cells usually requires purification steps that can result in significant yield
      reductions and loss of biological activity. Using insect cells as a model system
      to devise the means for secreting recombinant proteins that are not normally
      destined for secretion outside the producing cells, we initially examined the
      ability of an insect-specific signal peptide sequence to direct secretion of two
      intracellular proteins (the cytoplasmic enzyme chloramphenicol acetyl transferase
      [CAT] and the nuclear protein Bombyx mori chorion factor 1 [BmCF1]) expressed in
      transfected silkmoth cells. Although this signal sequence functioned efficiently
      as a chimera with normally secreted proteins, it failed to secrete CAT and BmCF1,
      suggesting that additional signals are required for passage of these polypeptides
      through the secretion pathway. For this reason, we also generated a secretion
      module consisting of the secreted protein juvenile hormone esterase (JHE), a
      spacer region containing a histidine tag and an endopeptidase cleavage site, to
      which coding sequences of choice can be cloned as C-terminal extensions. In C
      terminal fusions with the CAT and BmCF1 open reading frames, the N-terminal JHE
      moiety was able to provide all the signals necessary for secretion of CAT and
      BmCF1 into the extracellular environment. The histidine tag present in the spacer
      region allowed purification of fusion proteins by metal affinity chromatography
      under nondenaturing conditions, and the enteropeptidase cleavage site was
      recognized and cleaved by the cognate protease causing the release of the
      intracellular proteins from the secretion module. We also show that another
      secreted protein, human granulocyte-macrophage colony stimulating factor (GM-CSF)
      can substitute for JHE in the secretion module and that these secretion modules
      can function in mammalian cells.

PMID- 10944403
TI  - A decentralized multichannel length transformation algorithm and its parallel
      implementation for real-time ECG monitoring.
AB  - Multichannel algorithms have been developed for more accurate analysis of
      electrocardiograms (ECGs). Their benefit is the ability to use the information
      contained in all simultaneously acquired channels. In this paper we present a
      multichannel version of a nonsyntactic algorithm, based on length transformation.
      The proposed algorithm uses a decentralized schema for combining the results
      derived from each individual lead, instead of a global/centralized one (a spatial
      vector approach). Its performance was evaluated using the CSE database and real
      ECGs acquired by a 12-lead cardiograph. The results are also compared with
      previous-single-channel and multichannel-versions of the algorithm, showing a
      better performance. Since a multichannel algorithm is always a time-consuming
      task, it is rarely used in real-time monitoring systems. Motivated by this
      observation, we designed a parallel implementation of the proposed algorithm and
      tested its ability to be used in such systems.

PMID- 10944404
TI  - Disease management research using event graphs.
AB  - Event Graphs, conditional representations of stochastic relationships between
      discrete events, simulate disease dynamics. In this paper, we demonstrate how
      Event Graphs, at an appropriate abstraction level, also extend and organize
      scientific knowledge about diseases. They can identify promising treatment
      strategies and directions for further research and provide enough detail for
      testing combinations of new medicines and interventions. Event Graphs can be
      enriched to incorporate and validate data and test new theories to reflect an
      expanding dynamic scientific knowledge base and establish performance criteria
      for the economic viability of new treatments. To illustrate, an Event Graph is
      developed for mastitis, a costly dairy cattle disease, for which extensive
      scientific literature exists. With only a modest amount of imagination, the
      methodology presented here can be seen to apply modeling to any disease, human,
      plant, or animal. The Event Graph simulation presented here is currently being
      used in research and in a new veterinary epidemiology course.

PMID- 10944405
TI  - A closed-loop model of the canine cardiovascular system that includes ventricular
      interaction.
AB  - A closed-loop model of cardiopulmonary circulation has been developed for the
      study of right-left ventricular interaction under physiologically normal and
      altered conditions. The core model provides insight into the effects of
      ventricular interaction and pericardial mechanics on hemodynamics. The complete
      model contains realistic descriptions of (a) the interacting ventricular free
      walls and septum, (b) the atria, (c) the pericardium, and (d) the systemic and
      pulmonary vascular loads. The current analysis extends previous work on
      ventricular interaction and pericardial influence under isolated heart conditions
      to loading conditions imposed by a closed-loop model of the circulation. A
      nonlinear least-squares parameter identification method (Levenberg-Marquardt
      algorithm) is used, together with parameter sensitivity analysis, to estimate the
      values of key parameters associated with the ventricular and circulation models.
      Pressure measurements taken at several anatomical locations in the circulation
      during open-chest experiments on dogs are used as data in the identification
      process. The complete circulatory model, including septal and pericardial
      coupling, serves as a virtual testbed for assessing the global affects of
      localized mechanical or hemodynamic alterations. Studies of both direct and
      series ventricular interaction, as well as the effect of the pericardium on
      cardiac performance, are accomplished with this model. Alterations in model
      parameter values are used to predict the impact of disease and/or clinical
      interventions on steady-state hemodynamic performance. Additionally, a software
      package titled CardioPV has been developed to integrate the complete model with
      data acquisition tools and a sophisticated graphical user interface. The complete
      software package enables users to collect experimental data, use the data to
      estimate model parameters, and view the model outputs in an online setting.

PMID- 10944406
TI  - The reliability issue of computer-aided breast cancer diagnosis.
AB  - This paper introduces a number of reliability criteria for computer-aided
      diagnostic systems for breast cancer. These criteria are then used to analyze
      some published neural network systems. It is also shown that the property of
      monotonicity for the data is rather natural in this medical domain, and it has
      the potential to significantly improve the reliability of breast cancer diagnosis
      while maintaining a general representation power. A central part of this paper is
      devoted to the representation/narrow vicinity hypothesis, upon which existing
      computer-aided diagnostic methods heavily rely. The paper also develops a
      framework for determining the validity of this hypothesis. The same framework can
      be used to construct a diagnostic procedure with improved reliability.

PMID- 10944407
TI  - A statistical method for the analysis of positron emission tomography
      neuroreceptor ligand data.
AB  - A method for voxel by voxel statistical inference of PET radioligand receptor
      studies is presented. This method is aimed at detecting differences in
      radioligand binding between baseline and activation scans. It uses nonlinear
      least squares theory to estimate the ligand-receptor model parameters and
      utilizes the residuals to calculate their associated variance. The approach both
      increases the degrees of freedom for statistical testing and produces more
      accurate estimates of the standard deviation of the parameters. This technique is
      applicable to any ligand with a validated compartmental model, whether reversibly
      or irreversibly bound. The method was investigated and compared with a simple
      voxel-wise t test. Both simulated and real PET data for the dopamine D(1)
      receptor ligand [(11)C]SCH 23390 were used to assess the method. The assumptions
      implicit in the residuals methods were validated. The residuals method was found
      to be more sensitive than a simple t test, while not producing false-positive
      results. In addition, we showed that this method reliably differentiates changes
      in radioligand binding from the effects of changes in cerebral blood flow.

PMID- 10944408
TI  - Brain cortical activation during guitar-induced hand dystonia studied by
      functional MRI.
AB  - Focal hand dystonia in musicians is a strongly task-related movement disorder.
      Typically, symptoms become apparent only when players execute specific
      overpracticed skilled exercises on their instrument. We therefore examined five
      guitarists with functional MRI during dystonic symptom provocation by means of an
      adapted guitar inside the magnet. The activation patterns obtained in comparable
      nondystonic guitarists and in the study patients when performing normal-hand
      exercise served as references. A 1.5-T system equipped with echo-speed gradients
      and single-shot echoplanar imaging software was used. Data acquisition was
      centered on the cortical motor system encompassed in eight contiguous slices.
      Dystonic musicians compared with both control situations showed a significantly
      larger activation of the contralateral primary sensorimotor cortex that
      contrasted with a conspicuous bilateral underactivation of premotor areas. Our
      results coincide with studies of other dystonia types in that they show an
      abnormal recruitment of cortical areas involved in the control of voluntary
      movement. However, they do suggest that the primary sensorimotor cortex, rather
      than being underactive in idiopathic dystonic patients, may be overactive when
      tested during full expression of the task-induced movement disorder.

PMID- 10944409
TI  - Effects of dextroamphetamine on cognitive performance and cortical activation.
AB  - Monoaminergic neurotransmitters are known to have modulatory effects on cognition
      and on neurophysiological function in the cortex. The current study was performed
      with BOLD fMRI to examine physiological correlates of the effects of
      dextroamphetamine on working-memory performance in healthy controls. In a group
      analysis dextroamphetamine increased BOLD signal in the right prefrontal cortex
      during a task with increasing working-memory load that approached working-memory
      capacity. However, the effect of dextroamphetamine on performance and on signal
      change varied across individuals. Dextroamphetamine improved performance only in
      those subjects who had relatively low working-memory capacity at baseline,
      whereas in the subjects who had high working-memory capacity at baseline, it
      worsened performance. In subjects whose performance deteriorated, signal change
      was greater than that in subjects who had an improvement in performance, and
      these variations were correlated (Spearman rho = 0.89, P<0.02). These data shed
      light on the manner in which monoaminergic tone, working memory, and prefrontal
      function interact and, moreover, demonstrate that even in normal subjects the
      behavioral and neurophysiologic effects of dextroamphetamine are not homogeneous.
      These heterogeneic effects of dextroamphetamine may be explained by genetic
      variations that interact with the effects of dextroamphetamine.

PMID- 10944410
TI  - Neural correlates of episodic retrieval success.
AB  - Episodic memory retrieval involves multiple component processes, including those
      that occur when information is correctly remembered (retrieval success). The
      present study employed rapid-presentation event-related functional MRI that
      allowed different trial types with short intertrial intervals to be sorted such
      that the hemodynamic response associated with retrieval success could be
      extracted. Specifically, in an old/new episodic recognition task, hit trials
      (correctly recognized old items) and correct rejection trials (correctly rejected
      new items) were directly compared. The comparison revealed a mostly left
      lateralized set of brain regions. Differential activation was most robust in left
      lateral parietal cortex and medial parietal cortex. Additional regions of
      differential activation included left anterior prefrontal cortex at or near
      Brodmann area 10, anterior insula, thalamus, anterior cingulate cortex, frontal
      cortex along inferior frontal gyrus, premotor cortex, and presupplementary motor
      area. These results suggest that left frontal and parietal regions modulate
      activity based on the successful retrieval of information from episodic memory.
      We discuss these findings in the context of several recent investigations that
      provide converging results as well as prior studies that have failed to detect
      these changes.

PMID- 10944411
TI  - A CBF-based event-related brain activation paradigm: characterization of impulse
      response function and comparison to BOLD.
AB  - A perfusion-based event-related functional MRI method for the study of brain
      activation is presented. In this method, cerebral blood flow (CBF) was measured
      using a recently developed multislice arterial spin-labeling (ASL) perfusion
      imaging method with rapid spiral scanning. Temporal resolution of the perfusion
      measurement was substantially improved by employing intertrial subtraction and
      stimulus-shifting schemes. Perfusion and blood oxygenation level-dependent (BOLD)
      signals were obtained simultaneously by subtracting or adding the control and
      labeled images, respectively, in the same data sets. The impulse response
      function (IRF) of perfusion during brain activation was characterized for
      multiple stimulus durations and compared to the simultaneously acquired BOLD
      response. The CBF response curve preceded the BOLD curve by 0.21 s in the rising
      phase and 0.64 s in the falling phase. Linear additivity of the CBF and BOLD
      responses was assessed with rapidly repeated stimulations within single trials,
      and departure from linearity was found in both responses, characterized as
      attenuated amplitude and delayed rising time. Event-related visual and
      sensorimotor activation experiments were successfully performed with the new
      perfusion technique.

PMID- 10944412
TI  - Movement-related desynchronization of the cerebral cortex studied with spatially
      filtered magnetoencephalography.
AB  - Event-related desynchronization (ERD) within the alpha and beta bands on
      unilateral index finger extension and hand grasping was investigated on six
      normal volunteers with magnetoencephalography (MEG). A novel spatial filtering
      technique for imaging cortical source power, synthetic aperture magnetometry
      (SAM), was employed for the tomographic demonstration of ERD. SAM source image
      results were transformed into statistical parametric images. On the same hand
      grasping task, a functional MRI (fMRI) study was conducted on two subjects and
      compared with the ERD result. When the MEG data were analyzed with the fast
      Fourier transformation, power attenuation within the alpha and beta bands was
      evident on the contralateral sensorimotor area just prior to movement onset. The
      tomographic distribution of ERD was clearly obtained with SAM statistical imaging
      analysis. The equivalent current dipole (ECD) for the signal-averaged motor field
      was localized to the hemisphere contralateral to the hand movement, roughly at
      the center of the region displaying beta-band ERD. The signal increase on fMRI
      roughly colocalized with the ERD on the contralateral sensorimotor area. In
      conclusion, with the novel spatial filtering technique for the brain magnetic
      field, SAM, cortical regions contributing to ERD on finger movement were
      successfully demonstrated in a tomographic manner. The relative colocalization of
      the contralateral SAM ERD with ECD as well as the fMRI activation suggests that
      SAM is a practically useful technique to extract event-related signals from brain
      noise.

PMID- 10944413
TI  - Perilymphatic fluid compartments and intercellular spaces of the inner ear and
      the organ of Corti.
AB  - An in vitro preparation of the inner ear cochlea has been used to visualize the
      structural relationships of unfixed, living sensory cells and structural
      components within the intact hearing organ. By perfusing perilymphatic
      compartments of the cochlea with fluorochrome-conjugated dextran, the
      extracellular spaces were clearly outlined. The staining pattern illustrated the
      large fluid compartments formed by the tunnel of Corti, the space of Nuel, and
      the outer tunnel. The dextran solution also indicated the spaces between the
      outer hair cell rows, the inner hair cells, and the surrounding supporting cells.
      The staining pattern demonstrates that the organ of Corti has a loose structure,
      suggesting a weak mechanical coupling between the cells. Moreover, it is evident
      that substances applied to the perilymph (e.g., therapeutic drugs) will readily
      reach all the cells of the hearing organ. In addition to the intraorgan fluid
      compartments, the spiral limbus was shown to contain significant volumes of
      perilymph within the intercellular spaces forming the so-called teeth of Huschke
      between the interdental cells. An extensive system of bundles following the teeth
      of Huschke was shown to be completely immersed in perilymph. The bundles were
      stained by a potentiometric dye, which in the inner ear primarily stains nerve
      fibers and sensory cells, which may indicate a nervous control of cells in this
      region.

PMID- 10944414
TI  - Movement and mind: a functional imaging study of perception and interpretation of
      complex intentional movement patterns.
AB  - We report a functional neuroimaging study with positron emission tomography (PET)
      in which six healthy adult volunteers were scanned while watching silent computer
      presented animations. The characters in the animations were simple geometrical
      shapes whose movement patterns selectively evoked mental state attribution or
      simple action description. Results showed increased activation in association
      with mental state attribution in four main regions: medial prefrontal cortex,
      temporoparietal junction (superior temporal sulcus), basal temporal regions
      (fusiform gyrus and temporal poles adjacent to the amygdala), and extrastriate
      cortex (occipital gyrus). Previous imaging studies have implicated these regions
      in self-monitoring, in the perception of biological motion, and in the
      attribution of mental states using verbal stimuli or visual depictions of the
      human form. We suggest that these regions form a network for processing
      information about intentions, and speculate that the ability to make inferences
      about other people's mental states evolved from the ability to make inferences
      about other creatures' actions.

PMID- 10944415
TI  - Intersubject variability in cortical activations during a complex language task.
AB  - Intersubject variability in the functional organization of the human brain has
      theoretical and practical importance for basic and clinical neuroscience. In the
      present study, positron emission tomography (PET) and anatomical magnetic
      resonance imaging (MRI) were used to study the functional anatomy of language
      processes. Intersubject variability in task-induced activations in six brain
      regions was assessed in 20 normal subjects (10 men and 10 women) for frequency of
      occurrence, location, intensity, and extent. A complex, but well-studied task
      (overt verb generation) was compared to a simple baseline (visual fixation) to
      induce activations in brain areas serving perceptual, motoric, and cognitive
      functions. The frequency of occurrence was high for all selected brain areas (80
      95%). The variability in response location in Talairach space, expressed as the
      standard deviation along each axis (x, y, z), ranged from 5.2 to 9.9 mm. This
      variability appears to be uniformly distributed across the brain, uninfluenced by
      regional differences in the complexity of gyral anatomy or mediated behavior. The
      variability in response location, expressed as the average Euclidean distances
      (averaged across subjects) about mean locations of activations, varied from 9.40
      to 13.36 mm and had no significant differences by region (P>0.05, beta = 0.20).
      Intensity variability was also relatively small and homogenous across brain
      regions. In contrast, response extent was much more variable both across subjects
      and across brain regions (0.79 to 1.77, coefficient of variation). These findings
      are in good agreement with previous PET studies of intersubject variability and
      bode well for the possibility of using functional neuroimaging to study neural
      plasticity subsequent to congenital and acquired brain lesions.

PMID- 10944416
TI  - Automated 3-D extraction of inner and outer surfaces of cerebral cortex from MRI.
AB  - Automatic computer processing of large multidimensional images such as those
      produced by magnetic resonance imaging (MRI) is greatly aided by deformable
      models, which are used to extract, identify, and quantify specific neuroanatomic
      structures. A general method of deforming polyhedra is presented here, with two
      novel features. First, explicit prevention of self-intersecting surface
      geometries is provided, unlike conventional deformable models, which use
      regularization constraints to discourage but not necessarily prevent such
      behavior. Second, deformation of multiple surfaces with intersurface proximity
      constraints allows each surface to help guide other surfaces into place using
      model-based constraints such as expected thickness of an anatomic surface. These
      two features are used advantageously to identify automatically the total surface
      of the outer and inner boundaries of cerebral cortical gray matter from normal
      human MR images, accurately locating the depths of the sulci, even where noise
      and partial volume artifacts in the image obscure the visibility of sulci. The
      extracted surfaces are enforced to be simple two-dimensional manifolds (having
      the topology of a sphere), even though the data may have topological holes. This
      automatic 3-D cortex segmentation technique has been applied to 150 normal
      subjects, simultaneously extracting both the gray/white and gray/cerebrospinal
      fluid interface from each individual. The collection of surfaces has been used to
      create a spatial map of the mean and standard deviation for the location and the
      thickness of cortical gray matter. Three alternative criteria for defining
      cortical thickness at each cortical location were developed and compared. These
      results are shown to corroborate published postmortem and in vivo measurements of
      cortical thickness.

PMID- 10944417
TI  - Nitric oxide and peroxynitrite anion modulate liver plasma membrane fluidity and
      Na(+)/K(+)-ATPase activity.
AB  - Free radicals attack membranes and frequently alter their fluidity and function.
      The aim of the present work was to study the effect of nitric oxide (NO) radical
      and peroxynitrite anion on basolateral liver plasma membrane fluidity and on the
      activity of Na(+)/K(+)-ATPase. Basolateral membranes (BM) were isolated by
      ultracentrifugation in sucrose gradients and characterized enzymatically. BM were
      incubated with SNAP (a NO donor) or SIN-1 (a peroxynitrite donor). The release of
      NO or peroxynitrite was monitored by measuring NO(-)(2) + NO(-)(3). Relative
      fluidity was measured by polarization of fluorescence. NO increased membrane
      fluidity while peroxynitrite decreased it in a concentration-dependent manner.
      Na(+)/K(+)-ATPase activity was reduced by NO or peroxynitrite. Peroxynitrite
      anion inhibits ATPase activity in part by decreasing fluidity. However, it is
      very likely that both compounds inhibit ATPase activity by oxidation of the thiol
      groups of the enzyme. Our results suggest that NO may exert part of its
      biological effects by modulating membrane fluidity and function.

PMID- 10944418
TI  - Citrulline immunohistochemistry for demonstration of NOS activity in vivo and in
      vitro.
AB  - Nitric oxide (NO), a biomolecule with major cytotoxic potency, is generated by NO
      synthases (NOS) utilizing l-arginine as substrate and citrulline is formed as a
      "side product." In brain tissue, citrulline is considered to be produced
      exclusively by NOS, due to the incomplete urea cycle in the brain. We aimed to
      characterize NOS activity by citrulline immunostaining in different cell types of
      the brain under in situ conditions and in slice and culture experiments. NOS
      positive neurons and activated microglial cells were the most prominent
      citrulline-positive structures. Lack of citrulline immunoreaction in neurons of
      nNOS knockout mice emphasizes the dependency of citrulline positivity on NOS
      activity, and likewise there was no citrulline staining after application of the
      NOS inhibitors 7-nitroindazole and NIL. Interestingly, only a portion of NOS
      containing neurons costained for citrulline. The inhibition of argininosuccinate
      synthetase by alpha-methyl-dl-aspartate increased the number of citrulline
      positive cells, apparently due to reduction of the turnover rate of citrulline.
      Cells positive for NOS but negative for citrulline may indicate that the enzyme
      is either not activated or inhibited by cellular control mechanisms. The fact
      that not all citrulline-positive cells were NOS positive may be explained by an
      insufficient detection sensitivity or by disparate sites of citrulline production
      and recycling. The present results show that citrulline immunocytochemistry
      offers a viable and convenient means for studying NOS activity at the single-cell
      level to elicit its posttranslational control under physiological and
      pathophysiological conditions.

PMID- 10944419
TI  - Integrative effects of nitric oxide and endothelium-derived hyperpolarizing
      factor induced by acetylcholine and bradykinin in rat hindquarter perfusion.
AB  - We investigated the roles of endothelium-derived vasodilative factors in rat
      hindquarter perfusion using a system for the direct measurement of nitric oxide
      (NO). Acetylcholine (ACh) induced the dose-dependent release of NO with a
      concomitant decrease in perfusion pressure. Under the influence of N(G)
      monomethyl-l-arginine (l-NMMA), NO release in response to ACh was blocked, while
      the perfusion pressure still decreased. In the presence of tetraethylammonium
      (TEA), the decrease in perfusion pressure in response to ACh was attenuated
      compared to the control value. The decrease in perfusion pressure in response to
      ACh was almost abolished in the presence of both l-NMMA and TEA or with
      deendothelialization. Bradykinin (BK) also induced NO release and biphasic
      effects on the perfusion pressure. The perfusion pressure decreased with a lower
      concentration of BK and increased with a higher concentration. l-NMMA and TEA
      each abolished the decrease in perfusion pressure induced by BK. Furthermore, in
      the presence of both l-NMMA and TEA, the perfusion pressure actually increased in
      response to BK. These results suggest that ACh and BK induce vasodilation through
      NO release and a potassium channel dependent mechanism via endothelium.

PMID- 10944421
TI  - Evaluation of nitric oxide synthase activity and inhibition kinetics by
      chemiluminescence.
AB  - The binding affinity (K(I)) and inactivation rate (k(inact)) parameters of nitric
      oxide synthase (NOS) inhibitors are typically estimated by kinetic activity
      studies. Methods currently used in the estimation of these parameters frequently
      employ radiolabeled materials and require intensive sample preparation. We have
      devised a simple, reproducible, and sensitive method for the kinetic analysis of
      NOS activity and inhibition kinetics using chemiluminescence. We have used this
      method to characterize enzyme activity for purified murine macrophage nitric
      oxide synthase (NOS II). Using this method, we have also estimated the inhibitory
      parameters for a series of competitive antagonists and mechanism-based
      inactivators of NOS II. The estimated parameters are in agreement with those
      reported using other methods. We conclude that the chemiluminescence method can
      be used for kinetic studies of NOS activity and inhibition. This method
      represents a more efficient means for conducting kinetic studies of NOS
      inhibition.

PMID- 10944420
TI  - Inducible nitric oxide synthase knockout mouse macrophages disclose prooxidant
      effect of interferon-gamma on low-density lipoprotein oxidation.
AB  - To test our hypothesis that interferon-gamma (IFN-gamma) has a direct prooxidant
      effect on macrophage-mediated LDL oxidation behind its antioxidant effect via
      induction of inducible nitric oxide synthase (iNOS), we incubated LDL with wild
      type (iNOS(+/+)) or iNOS knockout mouse (iNOS(-/-)) macrophages preincubated with
      IFN-gamma or IFN-gamma plus lipopolysaccharide (IFN-gamma/LPS) for 24 h. LDL
      oxidation was measured in terms of formation of thiobarbituric acid reactive
      substances (TBARS) and electrophoretic mobility. Thiol production, nitrite
      production, and superoxide production from macrophages were measured by using
      Ellman's assay, the Griess reagent, and the SOD-inhibitable cytochrome c
      reduction method, respectively. IFN-gamma alone or combined with LPS induced iNOS
      expression and increased nitrite production in iNOS(+/+) macrophages, but not in
      iNOS(-/-) macrophages. TBARS formation from LDL was suppressed in IFN-gamma- and
      IFN-gamma/LPS-treated iNOS(+/+) macrophages but was increased in IFN-gamma
      treated iNOS(-/-) macrophages. In the presence of N(G)-monomethyl-l-arginine (l
      NMMA), a NOS inhibitor, the suppressive effect of IFN-gamma and IFN-gamma/LPS was
      abolished and TBARS formation was even increased to a level above that of
      untreated iNOS(+/+) macrophage. NOC 18, an NO donor, dose dependently inhibited
      macrophage-mediated LDL oxidation. IFN-gamma increased superoxide and thiol
      productions in both types of macrophages. We conclude that IFN-gamma promotes
      macrophage-mediated LDL oxidation by stimulating superoxide and thiol production
      under conditions where iNOS-catalyzed NO release is restricted.

PMID- 10944422
TI  - Survey of the allelic frequency of a NOS2A promoter microsatellite in human
      populations: assessment of the NOS2A gene and predisposition to infectious
      disease.
AB  - Allelic frequencies of a (CCTTT)(n) pentanucleotide repeat in the NOS2A promoter
      region were determined in a total of 1393 unrelated individuals from five
      specific population groups in four continents: Africa, Europe, Asia, and the
      Caribbean. There were highly significant differences in allele frequencies
      between the ethnically diverse populations. The repeat variation may have
      implications for the selective pressure of malaria or other infectious diseases
      that may operate at the NOS2 locus.

PMID- 10944423
TI  - Increased appearance of inducible nitric oxide synthase in the uterus and embryo
      at implantation.
AB  - The aim of this study was to investigate the presence of iNOS in the murine
      uterus and embryo at implantation. Western blot analysis showed the presence of a
      130-kDa band with strong reactivity to anti-iNOS antibody in the pre- and peri
      implantation stage uteri. This band was faint in the postimplantation uteri.
      Immunocytochemical studies showed a heavy localization of iNOS specifically on
      the apical cells of the uterine endometrium in the pre- and peri-implantation
      stages. But the postimplantation uteri showed resorbed endometrium showing weaker
      expression of iNOS. The iNOS was induced by estrogen and the induction was
      intensified when progesterone was given along with estrogen. This truly mimics
      the in vivo situation since implantation in mice occurs when an estrogen surge
      occurs on a background of progesterone. The embryos too express iNOS at the peri
      implantation stage. We suggest that iNOS expressed at peri-implantation would
      lead to enhanced NO production, which could act as a vasodilator and an
      angiogenic mediator. These effects could promote the attachment of the blastocyst
      to the uterus.

PMID- 10944424
TI  - Structure-reactivity studies of the Cu(2+)-catalyzed decomposition of four S
      nitrosothiols based around the S-Nitrosocysteine/S-nitrosoglutathione structures.
AB  - S-Nitrosoglutathione (GSNO) and the dipeptide derivative S
      nitrosoglutamylcysteine (SNO-GluCys) both at 1 x 10(-3) M in pH 7. 4 buffer
      containing added Cu(2+) (1 x 10(-5) M) are very unreactive toward decomposition
      (measured spectrophotometrically), and in both cases reaction stops at very low
      conversion. S-Nitrosocysteine (SNC) and the dipeptide derivative S
      nitrosocysteinylglycine (SNO-CysGly), on the other hand, are orders of magnitude
      more reactive under the same conditions, and reaction proceeds to completion.
      Initially, we interpreted these results in terms of the requirement of a suitably
      positioned free NH(2) group (which is available in both SNC and SNO-CysGly, but
      not in GSNO and SNO-GluCys) for efficient complexation of Cu(+), the effective
      reagent. However, later results measured at much lower substrate concentration (1
      x 10(-6) M) using the NO electrode system showed that at this concentration, all
      four S-nitrosothiols react at approximately the same rate and yield NO
      quantitatively. For GSNO the rate and percentage conversion were shown to drop
      progressively as the substrate concentration increases. All reactions are
      effectively halted in the presence of the metal ion chelator EDTA. The results
      can readily be explained in terms of complexation of Cu(2+) by the product
      disulfides from GSNO (i.e., GSSG) and SNO-GluCys, involving the glutamate
      residue, which is not present in SNC and SNO-CysGly. This is confirmed by the
      observed progressive reduction in yield and percentage conversion of GSNO
      decomposition as GSSG is added, at micromolar substrate concentrations.

PMID- 10944425
TI  - Suppression of bleomycin-induced nitric oxide production in mice by taurine and
      niacin.
AB  - The effects of taurine (T) and niacin (N) on the influx of inflammatory cells and
      nitric oxide (NO) levels in bronchoalveolar lavage fluid (BALF) and expression of
      inducible NO synthase (iNOS) mRNA and iNOS protein in lungs were evaluated in the
      bleomycin (BL)-mouse model of lung fibrosis. Mice were placed into four groups:
      saline-instilled (SA) with a control diet (CD) (SA + CD); saline-instilled with
      TN (1% taurine in water + 2.5% (w/w) niacin in diet) (SA + TN); BL-instilled with
      CD (BL + CD); and BL-instilled with TN treatment (BL + TN). There was no
      difference in differential cell counts in BALF between the SA + CD and SA + TN
      control groups. Intratracheal instillation (IT) of BL (0.1 U/mouse) in mice
      stimulated an early influx of neutrophils followed by an increase in lymphocytes
      and macrophages in the BL + CD group. Taurine and niacin treatment significantly
      reduced the numbers of neutrophils, lymphocytes, and macrophages in the BL + TN
      group and caused significant reductions in BL-induced increases in the lung
      hydroxyproline content at 14 and 21 days in the BL + TN group. The mice in the SA
      + CD and SA + TN control groups had low levels of NO in BALF, whereas mice in the
      BL + CD group as compared to the SA + CD control group had elevated levels of NO
      from day 3 through day 21. Taurine and niacin treatment caused significant
      reductions in BL-induced increases in NO levels in BALF from mice in the BL + TN
      group at 7, 14, and 21 days as compared to the corresponding BL + CD group. The
      increases in NO levels in BALF from the BL + CD group were associated with
      elevated levels of iNOS gene expression and protein in the lungs. RT-PCR analysis
      of total RNA isolated from the lungs indicated that taurine and niacin treatment
      suppressed the BL-induced increases in iNOS message and iNOS protein. The ability
      of taurine and niacin to suppress the BL-induced increased production of NO
      secondary to decreases in iNOS mRNA and protein appears to be one of the
      mechanisms for their anti-inflammatory and antifibrotic effects.

PMID- 10944426
TI  - Soluble nitric oxide donor and surfactant improve oxygenation and pulmonary
      hypertension in porcine lung injury.
AB  - Acute lung injury (ALI) is associated with diminished surfactant activity and
      pulmonary hypertension. NONOates are soluble NO donors which release NO in
      solution. Intratracheal NONOates reduce pulmonary hypertension and improve
      oxygenation in ALI. We hypothesized that the pharmacologic properties of NO
      donors would be unaltered after surfactant admixture in vitro and that
      aerosolized NONOate activity would be enhanced by surfactant pretreatment in
      vivo. NO donors were added to saline or surfactant and analyzed for
      nitrite/nitrate production and aortic ring vasodilation. Surfactant did not alter
      nitrate/nitrite production or aortic ring vasodilation. A porcine model of ALI
      with pulmonary hypertension was produced using intravenous oleic acid. Animals
      were assigned to Surfactant-Saline, Surfactant-NONOate, Saline-Saline, or Saline
      NONOate groups. Saline or surfactant was instilled into the trachea, followed by
      gas exchange, pulmonary function, and hemodynamic measurements. NONOate or saline
      was then aerosolized, and additional data were collected. Oxygenation was
      improved in the Surfactant-NONOate group, while pulmonary hypertension was
      selectively reduced in both NONOate groups. Aerosolized NONOate following
      surfactant pretreatment improves oxygenation and reduces pulmonary hypertension
      in ALI.

PMID- 10944427
TI  - Nitric oxide involvement in Drosophila immunity.
AB  - The augmented production of nitric oxide (NO) was observed during the hemocyte
      mediated melanotic encapsulation responses of Drosophila melanogaster and D.
      teissieri. When introduced into the hemocoel of D. melanogaster larvae, NO
      activated the gene encoding the antimicrobial peptide Diptericin. These
      observations, together with previous studies documenting the production of
      superoxide anion (O(*-)(2)) and H(2)O(2) in immune-challenged Drosophila, provide
      evidence that reactive intermediates of both oxygen (ROI) and nitrogen (RNI)
      constitute a part of the cytotoxic arsenal employed by Drosophila in defense
      against both microbial pathogens and eukaryotic parasites. These ROI and RNI
      appear to represent an evolutionarily conserved innate immune response that is
      mediated by regulatory proteins that are homologous to those of mammalian
      species.

PMID- 10944428
TI  - Evidence for a synergistic interaction between cadmium and endotoxin toxicity and
      for nitric oxide and cadmium displacement of metals in the kidney.
AB  - This study was undertaken to examine changes in Zn and Cu homeostasis in the
      liver and kidney of rats caused by cadmium (Cd) or lipopolysaccharide (LPS)
      administration. Twenty-five male, 7- to 8-week-old Wistar rats were divided into
      five groups: saline only treatment, saline treatment and food deprivation,
      exposure to a single dose of Cd, exposure to LPS alone, and exposure to Cd + LPS.
      Changes in plasma nitrate concentrations and hepatic and renal Zn and Cu contents
      were measured together with urinary excretion rates for the metals and nitrate on
      3 consecutive days: 24 h before treatment and 24 and 48 h after treatments. Cd
      exposure alone for 48 h caused a nearly 2-fold increase in plasma nitrate levels
      with no changes in urinary nitrate excretion whereas LPS treatment caused plasma
      nitrate levels to increase by 10-fold and urinary nitrate excretion to increase
      by 4-fold. Administration of LPS 24 h after Cd exposure caused a 10-fold increase
      in plasma nitrate concentrations and a 100-fold increase in urinary nitrate
      excretion compared to the rates prior to LPS administration. These results
      indicate a synergistic interaction between Cd and LPS toxicity. Cd exposure also
      caused a marked increase in hepatic Zn levels, but LPS did not cause any changes
      in hepatic Zn or Cu content. In sharp contrast, both Zn and Cu contents were
      decreased in the kidneys by 16 and 36% in animals exposed to Cd or LPS. A
      correlation analysis of measured variables reveals that renal Cu contents were
      inversely associated with plasma nitrate concentrations while urinary Cu
      excretion on day 3 showed a strong positive correlation with both urinary nitrate
      and Cd excretions on the same day. A linear regression analysis shows 20% of the
      variation in urinary Cu excretion was associated with urinary Cd excretion on the
      same day. It is concluded that reductions in renal Cu contents caused by Cd or
      LPS administration may be a result of Cd and NO displacement of Cu previously
      bound to metallothionein.

PMID- 10944429
TI  - Nitric oxide dysfunction in the pathophysiology of preeclampsia.
AB  - Researchers disagree as to the importance of nitric oxide (NO) in preeclampsia.
      Many researchers have alluded to NO's possible primary or secondary role in the
      development of preeclampsia, but few have correlated the dysfunction of nitric
      oxide production with the other metabolic derangements seen in this condition.
      This paper will review the evidence that the primary dysfunction in preeclampsia
      is a relative deficiency of available NO (secondary to oxidative degradation) and
      an excess of peroxynitrite (ONOO(-)). The combination of a deficiency of NO and
      an increase in ONOO(-) can directly or indirectly initiate the vast majority of
      physiological and serological changes associated with preeclampsia, such as blood
      pressure, increased glomerular filtration rate, proteinuria, platelet
      dysfunction, increased thromboxane and endothelin, and a decrease in
      prostacyclin. Understanding the complex role of nitric oxide in this condition
      may explain why previous interventions have been unsuccessful and suggest
      possible strategies for prevention and treatment in the future.

PMID- 10944430
TI  - Differential regulation of phospholipase C-beta isozymes in cardiomyocyte
      hypertrophy.
AB  - Cardiac hypertrophy is a major predictor of heart failure and of morbidity and
      mortality in developed countries. Many hormones and growth factors induce cardiac
      hypertrophy via activation of members of the phospholipase C (PLC) family. The
      expression pattern of the PLCbeta isozyme subfamily was investigated in neonatal
      rat cardiomyocytes after stimulation with different hypertrophic stimuli. Under
      control conditions and after stimulation with norepinephrine, cardiomyocytes
      expressed similar amounts of PLCbeta3 mRNA. In the presence of fetal calf serum
      (FCS), additional expression of PLCbeta1 was induced. Growth hormone (GH) and
      insulin-like growth factor-I (IGF-I) both induced a substantial increase in
      PLCbeta3 mRNA expression. The response to GH could not be abolished by the IGF-I
      receptor blocker IGF-I analogue indicating an IGF-I-independent action of GH. The
      upregulation of PLCbeta3 by IGF-I was abolished by preincubation of
      cardiomyocytes with the IGF-I receptor antagonist IGF-I analogue, the tyrosine
      kinase inhibitor genistein, the extracellular signal-related kinase (ERK)
      inhibitor PD 98059, the phosphatidylinositol-3- (PI-3) kinase inhibitor
      wortmannin and the p70 S6 kinase inhibitor rapamycin. Induction of the immediate
      early genes c-myc, c-fos, and c-jun by IGF-I was abolished by preincubation with
      antisense oligos against PLCbeta3. It is concluded that the expression of PLCbeta
      isozymes in cardiomyocytes is differentially regulated by different hypertrophic
      stimuli. The upregulation of PLCbeta3 by IGF-I is dependent on the activity of
      tyrosine kinase, ERK, PI3 kinase, and p70 S6 kinase and PLCbeta3 expression seems
      to be required for the induction of immediate early genes by IGF-I. The
      involvement of the PLCbeta subfamily in signal transduction of receptors other
      than G-protein-coupled receptors is suggested.

PMID- 10944431
TI  - Effect of 17-beta-estradiol and progesterone on angiotensin II-induced changes in
      inositol-1,4,5-trisphosphate content and protein kinase C activity in anterior
      pituitary.
AB  - Angiotensin II (AngII) is known to act in the anteriorpituitary through
      phosphatidiloinositol breakdown, increasing the level of inositol-1,4,5
      trisphosphate (IP(3)) and diacyloglycerol (DAG), a potential activator of protein
      kinase C (PKC). We examined the effect of estradiol and progesterone treatment in
      vivo on IP(3) levels and activity of PKC under the influence of AngII. Three
      groups of intact female rats received in vivo injections of 17-beta-estradiol,
      progesterone, and oil (control) for five days, and then the in vitro effect of
      AngII was examined using homogenate of the anterior pituitary. AngII increased
      either the IP(3) concentration or the synapsin I phosphorylation catalyzed by
      PKC. Estradiol enhanced the basal (without AngII) IP(3) level and PKC activity
      induced by AngII. Progesterone did not change the basal and AngII-induced IP(3)
      concentrations. On the other hand, it decreased the basal PKC activity and
      blocked the effect of AngII. Our data suggest that ovarian steroids can modulate
      the effect of AngII on the anterior pituitary gland.

PMID- 10944432
TI  - Immunochemical detection of protein dityrosine in atherosclerotic lesion of apo-E
      deficient mice using a novel monoclonal antibody.
AB  - Dityrosine is one of the specific biomarkers for proteinoxidation. We prepared an
      antibody specific for proteindityrosine using a dimer of 3-p
      (hydroxyphenyl)propionic acid (di-HP) as a hapten. Three clones (A8, G6, and 1C3)
      were obtained, and the antibody from the A8 clone reacted with the di-HP
      conjugated protein but not with a dityrosine conjugate. The others (G6 and 1C3
      clones) recognized both the di-HP and dityrosine conjugates. The antibodies
      reacted with peptidyl dityrosine, derived from Thr-Tyr-Ser, rather than the free
      dityrosine. The reactivity of the latter two antibodies with lens proteins
      oxidized by incubation with H(2)O(2)/Cu was in good accordance with the formation
      of the dityrosine-like fluorescence. Using the obtained monoclonal antibody, the
      immunopositive staining of atherosclerotic lesions in Apo E-deficient mice was
      confirmed by an immunohistochemical technique.

PMID- 10944433
TI  - Activation of the Akt/FKHRL1 pathway mediates the antiapoptotic effects of
      erythropoietin in primary human erythroid progenitors.
AB  - Erythropoietin (Epo), stem cell factor (SCF), and insulin-like growth factor-1
      (IGF-1) are key regulators of erythroid cell proliferation and differentiation.
      To understand the mechanisms of generation of signals by each of these growth
      factors, we determined the activation of the PI3-kinase/Akt pathway during
      proliferation and differentiation of primary human erythroid progenitors. Our
      results demonstrate that PKB/Akt is activated by Epo and SCF, but not by IGF-1 in
      human primary erythroid progenitors. In addition, Epo treatment of erythroid
      progenitors induces phosphorylation of a member of the Forkhead family (FH) of
      transcription factors FKHRL1, downstream of activation of the Akt kinase. Such
      Epo-dependent activation of FKHRL1 apparently regulates the generation of Epo
      dependent antiapoptotic signals as evidenced by the induction of apoptosis of
      erythroid progenitors during treatment of cells with the PI3-kinase (PI3K)
      inhibitor LY294002. Thus, the PI3K/Akt/FKHRL1 pathway is essential for inhibition
      of apoptosis in response to Epo and SCF, while the IGF-1 receptor utilizes a
      different pathway.

PMID- 10944434
TI  - C-phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro.
AB  - C-Phycocyanin (from Spirulina platensis) effectively inhibited CCl(4)-induced
      lipid peroxidation in rat liver in vivo. Both native and reduced phycocyanin
      significantly inhibited peroxyl radical-induced lipid peroxidation in rat liver
      microsomes and the inhibition was concentration dependent with an IC(50) of 11.35
      and 12.7 microM, respectively. The radical scavenging property of phycocyanin was
      established by studying its reactivity with peroxyl and hydroxyl radicals and
      also by competition kinetics of crocin bleaching. These studies have demonstrated
      that phycocyanin is a potent peroxyl radical scavenger with an IC(50) of 5.0
      microM and the rate constant ratios obtained for phycocyanin and uric acid (a
      known peroxyl radical scavenger) were 1.54 and 3.5, respectively. These studies
      clearly suggest that the covalently linked chromophore, phycocyanobilin, is
      involved in the antioxidant and radical scavenging activity of phycocyanin.

PMID- 10944436
TI  - A polymorphism in the growth hormone (GH)-releasing hormone (GHRH) receptor gene
      is associated with elevated response to GHRH by human pituitary somatotrophinomas
      in vitro.
AB  - A previous study has suggested that a G to A base change at position 169 of the
      GHRH-receptor gene in human somatotrophinomas is a mutation and confers
      hypersensitivity to GHRH. The alternative base converts codon 57 from GCG to AGC,
      resulting in replacement of alanine (Ala) with threonine (Thr). In the present
      study, two of five human GH-secreting somatotrophinomas were found to possess the
      codon 57 AGC sequence. The GCG allele was also detected, indicating
      heterozygosity. However, the patients' normal blood-derived DNA also yielded the
      same sequence pattern, indicating that the Ala --> Thr amino acid change is a
      normal polymorphism, and not a somatic mutation. Nevertheless, in vitro, the
      tumors possessing the Ala --> Thr amino acid change responded very strongly to
      GHRH in terms of cAMP formation, being increased 40- and 200-fold, in comparison
      to the 2-fold increases by tumors without the alternative GHRH-receptor sequence.
      Likewise, the in vitro response of GH secretion to GHRH was elevated. One of the
      two tumors with the alternative Thr residue, and the highest responder to GHRH,
      possessed a gsp mutation, despite the fact that these defects are thought to
      reduce responsiveness to GHRH. These results fail to confirm that the GCG --> AGC
      at codon 57 of the GHRH-receptor gene is a mutation, but do support the concept
      that the alternative form with Thr confers increased sensitivity to GHRH.

PMID- 10944435
TI  - Phosphorylation of AZT-resistant human immunodeficiency virus type 1 reverse
      transcriptase by casein kinase II in vitro: effects on inhibitor sensitivity.
AB  - Casein kinase II (CKII) phosphorylates wild-type (WT) recombinant reverse
      transcriptase (RT) mainly in the p66 subunit in vitro. Phosphorylation of T215F
      RT and D67N/K70R/T215F/K219Q RT (AZT-resistant RT) in vitro increases
      discrimination against AZTTP 2. 5- and 3.6-fold, respectively. This in vitro
      resistance can be reversed by treatment of phosphorylated AZT-resistant RT with
      phosphatase. Phosphorylation has no effect on WT RT. Terminal transferase
      activity of RT is selectively suppressed on phosphorylated AZT-resistant RT.
      Resistance to phosphonoformic acid (PFA, foscarnet) increases 3-fold upon
      phosphorylation of AZT-resistant RT. Although T215, the most important residue
      for AZT-resistance, is part of a CKII consensus target site, serines are
      primarily phosphorylated relative to threonines. Mutational analysis shows that
      phosphorylation can be reduced to 10% that of WT when amino-acid changes are
      introduced both in the "fingers" subdomain and motif D. These results suggest
      that phosphorylation of RT might be one factor involved in drug resistance in
      vivo.

PMID- 10944437
TI  - Cloning, genomic organization, and tissue distribution of human Ssf-1.
AB  - During the screening of a human placenta cDNA library, realized in order to
      isolate the P2Y(11) coding sequence, an unrelated cDNA was cloned. We identified
      a 1422 bp open reading frame encoding a human protein displaying 40% amino acid
      identity with the Saccharomyces cerevisiae Ssf-1, a protein involved in the
      second step of mRNA splicing. Sequencing of the corresponding genomic DNA showed
      that the gene encoding human Ssf-1 is located upstream to the P2Y(11) gene on
      chromosome 19p31. Comparison of the cDNA and genomic DNA sequences revealed that
      the human Ssf-1 gene is split into 12 exons. Northern blotting experiments showed
      that the 1.7 kb Ssf-1 mRNA presents an ubiquitous tissue expression. We also show
      that, in HL-60 human promyelocytic leukemia cells, Ssf-1 mRNA is rapidly
      upregulated following a treatment by granulocyte-colony stimulating factor and
      dibutyryl-cyclicAMP, two agents known to induce the granulocytic differentiation
      of these cells.

PMID- 10944438
TI  - Membrane association of presynaptic cytomatrix protein bassoon.
AB  - Components of the specialized cytomatrix at active zones of presynaptic nerve
      terminals are thought to be involved in organizing synaptic events such as
      immobilisation or translocation of synaptic vesicles and assemblingactive zone
      components. The 420-kDa non-transmembraneprotein Bassoon is a specific
      componentof the presynaptic cytomatrix that shares features with both
      cytoskeleton-associated and peripheral-membrane proteins. Using immunogold
      electron microscopy we show here that synapse associated Bassoon is distributed
      in a subregion of active zones. Using a biochemical assay we show that a fraction
      of Bassoon is membrane associated. Electron microscopy performed on the same
      biochemical fraction further revealed that Bassoon is associated with vesicular
      structures. Together these data suggest that at least a fraction of Bassoon is
      associated with a membraneous compartment in neurons.

PMID- 10944439
TI  - Gene structure and chromosomal mapping of human epithelial calcium channel.
AB  - The epithelial Ca(2+) channel, ECaC, represents the rate-limiting step of vitamin
      D(3)-regulated Ca(2+) (re)absorption in kidney and intestine, and provides,
      therefore, a new candidate gene for Ca(2+)-related disorders. To supply the basis
      for direct mutation analysis, we report here the structure of the human ECaC gene
      (ECAC1(2)). It consists of 16 exons spanning 25 kb with introns ranging from 98
      to 8500 bp. The 5'-flanking region of ECAC1 contains four putative vitamin D(3)
      responsive elements. At positions -92 and -13 transcription initiation sites were
      identified, but the former lacks the canonical TATA or CAAT boxes. ECAC1 was
      mapped to chromosome 7q35 by fluorescent in situ hybridization, reassigning a
      previous radiation hybrid mapping to 7q31.1-2. The gene of a recently identified
      rat intestine homologue of ECaC, named Ca(2+) transporter 1, was found juxtaposed
      to the ECaC gene, indicating that both genes are the products of evolutionary
      local gene duplication.

PMID- 10944440
TI  - Effect of advanced glycation end products on lens epithelial cells in vitro.
AB  - The extended exposure of proteins to reducing sugars leads to nonenzymatic
      glycation with the accumulation of advanced glycation end products (AGEs). Long
      lived proteins, such as collagen and crystallins, are subjected to this
      modification, and are implicated as causal factors in several diseases including
      diabetic complications, cataracts, and arteriosclerosis. One means through which
      AGEs modulate cellular interactions is via binding to specific receptors. In the
      current study, the existence of AGEs in human anterior polar lens capsules of
      cataracts was confirmed using a combination of dot-immunoblot and fluorescent
      detection. Human lens epithelial cells (LECs) attached to anterior lens capsules
      expressed mRNA for the receptor for AGEs (RAGE). The interaction of LECs with
      AGEs using bovine lens epithelial explants demonstrated that AGEs induced mRNAs
      and proteins of fibronectin, collagen type I, aberrant extracellular matrix
      proteins, and alpha-SMA, a specific marker for myofibroblastic cells. These
      findings suggest that AGEs may alter cellular functions which induce mRNAs and
      proteins associated with fibrosis in LECs.

PMID- 10944441
TI  - Cancer cell-derived interleukin 1alpha contributes to autocrine and paracrine
      induction of pro-metastatic genes in breast cancer.
AB  - Invasion and metastasis of cancer cells is a complex process requiring the
      activity of proteins that promote extracellular matrix degradation, motility of
      cancer cells, and angiogenesis. Although exclusively the cancer cells make
      several of these proteins, few key proteins are derived from stromal cells in
      response to cancer cell-stromal cell interaction. In this report, we show that
      the breast cancer cell-derived interleukin-1alpha (IL-1alpha) plays an important
      role in expression of pro-metastatic genes in cancer as well as in stromal cells.
      Neutralizing antibody against IL-1alpha inhibited IL-6, and IL-8 expression in IL
      1alpha-expressing cancer cells. In addition, this antibody also prevented
      induction of IL-6, IL-8, and matrix metalloproteinase 3 (MMP3) but not vascular
      endothelial growth factor (VEGF) in fibroblasts by conditioned medium (CM) from
      IL-1alpha-expressing breast cancer cells. These results suggest that inhibition
      of IL-1alpha activity by either neutralizing antibody against IL-1alpha or
      chemical inhibitor of IL-1alpha processing may prevent invasion and metastasis of
      breast cancer.

PMID- 10944442
TI  - Combined enzymatic complex I and III deficiency associated with mutations in the
      nuclear encoded NDUFS4 gene.
AB  - Combined OXPHOS-system enzyme deficiencies are observed in approximately 25% of
      all OXPHOS-system disturbances. Of these, combined complex I and III deficiency
      is relatively scarce. So far, only mtDNA and thymidine phosphorylase (TP)
      mutations have been associated with combined OXPHOS-system disturbances. In this
      report we show, for the first time, that a nuclear gene mutation in a structural,
      nuclear encoded complex I gene is associated with combined complex I and III
      deficiency. After our initial report we describe mutations in the NDUFS4 gene of
      complex I in two additional patients. The first mutation is a deletion of G at
      position 289 or 290. Amino acid 96 changes from a tryptophan to a stop codon. The
      mutation was found homozygous in the patient; both parents are heterozygous for
      the mutation. The second mutation is a transition from C to T at cDNA position
      316. Codon is changed from CGA (arginine) to TGA (stop). The patient is
      homozygous for the mutation; both parents are heterozygous. Both mutations in the
      NDUFS4 gene led to a premature stop in Leigh-like patients with an early lethal
      phenotype. We hypothesise that the structural integrity of the OXPHOS system, in
      mammal supermolecular structures, may be responsible for the observed biochemical
      features.

PMID- 10944443
TI  - Characterization of p40/GPR69A as a peripheral membrane protein related to the
      lantibiotic synthetase component C.
AB  - The 40 kDa erythrocyte membrane protein p40/GPR69A, previously assigned to the G
      protein-coupled receptor superfamily, was now identified by peptide-antibodies
      and characterized as a loosely associated peripheral membrane protein. This
      result is in striking contrast to the proposed seven-transmembrane protein
      structure and function and therefore we wish to correct our previous proposal.
      p40 is located at the cytoplasmic side of the membrane and is neither associated
      with the cytoskeleton nor lipid rafts. Refined sequence analysis revealed that
      p40 is related to the LanC family of bacterial membrane-associated proteins which
      are involved in the biosynthesis of antimicrobial peptides. Therefore, we rename
      p40 to LanC-like protein 1 (LANCL1) and suggest that it may play a similar role
      as a peptide-modifying enzyme component in eukaryotic cells.

PMID- 10944444
TI  - The use of the substrate-heme complex approach in the design, synthesis,
      biochemical evaluation, and rationalization of the inhibitory activity of a range
      of azole compounds against cholesterol side chain cleavage enzyme.
AB  - Here, we report the synthesis and biochemical evaluation of a number of compounds
      as potent inhibitors of cytochrome P450 enzymes, such as aromatase (AR), but not
      cholesterol side chain cleavage (CSCC). This is a crucial enzyme in the steroidal
      cascade and its inhibition results in major side-effects, as a result, the
      ability of compounds to specifically inhibit enzymes such as AR but not CSCC
      would be an important factor in the drug design process.

PMID- 10944445
TI  - Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.
AB  - Proteinase-activated receptors (PARs) are activated by proteolytic removal of a
      short amino terminal peptide, thus exposing a new amino terminus that functions
      as a tethered ligand that activates the receptor. With the aim to identify and
      study potential activators of PAR-2 we have developed a new method to measure
      proteolytic cleavage of PARs. PAR-2 was tagged with the insulin C-peptide that
      upon receptor cleavage is released and quantified using an ELISA. The modified
      receptor, shown to be functional in mouse 3T3 cells, was expressed in an insect
      cell line and the ability of different proteinases to cleave PAR-2 was studied.
      Two different mast cell tryptases cleaved PAR-2 in a concentration dependent
      manner, but were much less potent than pancreatic trypsin and trypsin-2 isolated
      from a carcinoma cell line. Pancreatic trypsin and trypsin-2 were almost equally
      effective at cleaving PAR-2 suggesting that extrapancreatic trypsins are
      potential in vivo activators of PAR-2.

PMID- 10944446
TI  - Baculoviral display of functional scFv and synthetic IgG-binding domains.
AB  - Viral vectors displaying specific ligand binding moities such as scFv fragments
      or intact antibodies hold promise for the development of targeted gene therapy
      vectors. In this report we describe baculoviral vectors displaying either
      functional scFv fragments or the synthetic Z/ZZ IgG binding domain derived from
      protein A. Display on the baculovirus surface was achieved via fusion of the scFv
      fragment or Z/ZZ domain to the N-terminus of gp64, the major envelope protein of
      the Autographa californica nuclear polyhedrosis virus, AcNPV. As examples of scFv
      fragments we have used a murine scFv specific for the hapten 2-phenyloxazolone
      and a human scFv specific for carcinoembryonic antigen. In principle, the Z/ZZ
      IgG binding domain displaying baculoviruses could be targeted to specific cell
      types via the binding of an appropriate antibody. We envisage applications for
      scFv and Z/ZZ domain displaying baculoviral vectors in the gene therapy field.

PMID- 10944447
TI  - px(2), the newly identified gene in Rhizobium leguminosarum, is characterized to
      enhance its adjacent nodF expression.
AB  - nodFEL operon is one of the NodD-dependent inducible nod operons that is
      clustered on the symbiosis plasmid of Rhizobium leguminosarum biovar viciae. A
      recent study on the upstream regulatory region of nodFEL operon had identified a
      new promoter, which was responsible for the transcription of a 0.72 Kb RNA
      molecule, called px(2), in the opposite direction to nodF. This new promoter was
      further characterized to overlap with that of nodF and its in vitro transcription
      was inhibited by another newly identified nod regulator, Px. In this paper we
      report that the sequence analysis of the px(2) transcript revealed only one open
      reading frame (ORF(66)), corresponding to a polypeptide of 66 amino acids.
      Moreover, the increase in px(2) copy numbers enhanced the in vivo inducible
      expression level of nodF, whereas the frame-shift mutation of ORF(66) eliminated
      such effect, providing evidence that px(2) is responsible for specifically
      upregulating nodF expression. This result also raises the big possibility that
      px(2) encodes this polypeptide. A model for coordinated expression of px(2) and
      nodF, transcribed divergently from each other, is proposed.

PMID- 10944448
TI  - Characterization of interaction of C- and N-terminal domains in LIM15/DMC1 and
      RAD51 from a basidiomycetes, Coprinus cinereus.
AB  - Both LIM15/DMC1 and RAD51 are thought to be essential for meiosis in which
      homologous chromosomes pair and recombine. The primary purpose of the present
      study was to investigate the homotypic and heterotypic interactions among their
      terminal domains. We prepared cDNAs and recombinant proteins of the full-length,
      N-terminal, and the C-terminal domains of LIM15/DMC1 (CoLIM15) and RAD51
      (CoRAD51) from the basidiomycete Coprinus cinereus. In both two-hybrid assay in
      vivo and pull-down assay in vitro, either CoLim15 or CoRad51 interacted
      homotypically between the C-terminal domains, respectively, but no heterotypic
      interaction was observed between CoLim15 and CoRad51. The N-terminal domain of
      CoLim15 bound to ssDNA and dsDNA, while the C-terminal domain of CoRad51 appeared
      to interact weakly with ssDNA. Based on these results, the interaction among the
      strand-exchange proteins and meiosis was discussed.

PMID- 10944449
TI  - Glucose-6-phosphatase in the insulin secreting cell line INS-1.
AB  - The glucose-6-phosphatase system of the glucose sensitive insulin secreting rat
      insulinoma cells (INS-1) was investigated. INS-1 cells contain easily detectable
      levels of glucose-6-phosphatase enzyme protein (assessed by Western blotting) and
      have a very significant enzymatic activity. The features of the enzyme (Km and
      Vmax values, sensitivity to acidic pH, partial latency, and double immunoreactive
      band) are similar to those of the hepatic form. On the other hand, hardly
      detectable levels of glucose-6-phosphatase activity and protein were present in
      the parent glucose insensitive RINm5F cell line. The mRNA of the glucose-6
      phosphate transporter was also more abundant in the INS-1 cells. The results
      support the view that the glucose-6-phosphatase system of the beta-cell is
      associated with the regulation of insulin secretion.

PMID- 10944450
TI  - WISP-2 as a novel estrogen-responsive gene in human breast cancer cells.
AB  - In order to search for novel estrogen-responsive genes, we performed serial
      analysis of gene expression (SAGE) for estrogen-treated MCF-7 human breast cancer
      cells. SAGE analysis of 31,000 and 30,856 tags from non-treated and 17 beta
      estradiol (E2)-treated cells for 24 h, respectively, facilitated the
      identification of 15,037 different transcripts. Comparison of these two SAGE
      libraries indicated a remarkable similarity in expression profiles. Among the
      identified transcripts, four genes were found to be markedly increased for E2
      treated cells compared with control cells. Three of the transcripts were
      cathepsin D, pS2 and high mobility group 1 protein, which have been described as
      estrogen-inducible genes. The fourth gene was WISP-2 (Wnt-1 inducible signaling
      pathway protein 2) which has recently been reported as an up-regulated gene in
      the mammary epithelial cell line C57 MG transformed by the Wnt-1 oncogene. The
      increase in WISP-2 mRNA was completely prevented by co-incubation with a pure
      anti-estrogen ICI 182,780, but not by coincubation with cycloheximide, indicating
      that WISP-2 is directly regulated by the estrogen receptor. The WISP-2 gene was
      also induced by treating with environmental estrogens, such as bisphenol-A or
      nonylphenol. This study represents the first comprehensive gene expression
      analysis of estrogen-treated human breast cancer cells.

PMID- 10944451
TI  - Retinoblastoma protein phosphorylation via PI 3-kinase and mTOR pathway regulates
      adipocyte differentiation.
AB  - In the early phase of adipocyte differentiation, transient increase of DNA
      synthesis, called clonal expansion, and transient hyperphosphorylation of
      retinoblastoma protein (Rb) are observed. We investigated the role of these
      phenomena in insulin-induced adipocyte differentiation of 3T3-L1 cells. Insulin
      induced clonal expansion, Rb phosphorylation and adipocyte differentiation were
      all inhibited by the PI 3-kinase inhibitors and rapamycin, but not the MEK
      inhibitor, whereas the MEK inhibitor, but not PI 3-kinase inhibitors or
      rapamycin, decreased c-fos induction. We conclude that insulin induces
      hyperphosphorylation of Rb via PI 3-kinase and mTOR dependent pathway, which
      promotes clonal expansion and adipocyte differentiation of 3T3-L1 cells.

PMID- 10944452
TI  - Molecular cloning, functional characterization, and gene expression of a follicle
      stimulating hormone receptor in the testis of newt Cynops pyrrhogaster.
AB  - We previously demonstrated in vitro that mammalian follicle-stimulating hormone
      (FSH) stimulates the proliferation of newt secondary spermatogonia and their
      differentiation into primary spermatocytes. In the current study, we isolated a
      cDNA from newt testis that encodes a FSH receptor (FSH-R). The total sequence
      homology in the deduced protein of the newt was approximately 70% with mammalian
      FSH-Rs. Mammalian cells, transiently transfected with the cloned newt FSH-R cDNA,
      displayed specific binding to [(125)I] human FSH and cAMP accumulation,
      indicating that the cloned cDNA encodes a functional newt FSH-R protein. Northern
      blot analysis revealed a single transcript of approximately 3.0 kb length that
      was synthesized in testicular somatic cells (mainly Sertoli cells) from
      spermatogonial to spermatid stages with the highest level expressed during the
      primary spermatocytes stage. These results demonstrate that FSH stimulates newt
      spermatogenesis through the FSH-R. This study, as far as we know, reports for the
      first time the cloning of an amphibian FSH-R cDNA.

PMID- 10944453
TI  - Chemotaxis and biodegradation of 3-methyl- 4-nitrophenol by Ralstonia sp. SJ98.
AB  - 3-Methyl-4-nitrophenol is one of the major breakdown products of fenitrothion
      [O,O-dimethyl O-(3-methyl-4-nitrophenyl) thiophosphate], a recalcitrant
      organophosphate insecticide used in agriculture. Being the non-polar methylated
      aromatic compound, 3-methyl-4-nitrophenol is highly toxic and, therefore, a
      complete degradation of this compound is important for environmental
      decontamination/bioremediation purposes. A gram negative, motile Ralstonia sp.
      SJ98 was isolated by selective screening from a soil sample contaminated with
      pesticides. The microorganism was capable of utilizing 3-methyl-4-nitrophenol as
      the sole source of carbon and energy. Thin layer chromatography (TLC), gas
      chromatography (GC), gas chromatography-mass spectrometry (GC-MS), and high
      performance liquid chromatography (HPLC) were performed to determine the possible
      intermediates in the degradative pathway of this compound. Taken together,
      catechol was found to be one of the major intermediate of the pathway.
      Furthermore, the chemotactic behavior of Ralstonia sp. SJ98 towards 3-methyl-4
      nitrophenol was tested using three different methods i.e., drop assay, swarm
      plate assay and capillary assay, which were found to be positive towards this
      compound. This is the first report clearly indicating the involvement of a
      microorganism in the chemotaxis and biodegradation of methyl-4-nitrophenol and
      formation of catechol as an intermediate in the degradative pathway.

PMID- 10944454
TI  - Mapping and determination of the cDNA sequence of the Erc gene preferentially
      expressed in renal cell carcinoma in the Tsc2 gene mutant (Eker) rat model.
AB  - The Eker rat develops hereditary renal carcinomas (RCs) due to two hit mutations
      of the tumor suppressor gene, Tsc2. We previously identified using
      representational difference analysis (RDA), four genes that were expressed more
      abundantly in an Eker rat RC cell line than in normal kidney tissue. One gene,
      Erc (expressed in renal carcinoma) showed sequence homology to the mouse and
      human megakaryocyte potentiating factor (MPF)/mesothelin gene. The present study
      determines the full sequence of the cDNA and the exon-intron structure of the rat
      Erc gene and maps its locus in the chromosome by fluorescence in situ
      hybridization. Rat Erc and its human homologue were localized in chromosomes
      10q12-21 and 16p13.3, respectively, both of which coincided with the locus of the
      Tsc2/TSC gene. We also found that Erc was expressed at higher levels in primary
      RCs compared with the normal kidney of the Eker rat. Erc may be related to
      carcinogenesis in the Tsc2 gene mutant (Eker) rat model.

PMID- 10944455
TI  - RBP95, a novel leucine zipper protein, binds to the retinoblastoma protein.
AB  - We recently identified a novel cDNA encoding a retinoblastoma protein (pRb)
      associated protein. It was named RBP95, which was composed of 838 amino acid
      residues with a calculated molecular size of 94,789 Da. Northern blot analysis
      showed a single mRNA of about 4. 5 kb ubiquitously expressed in human tissues. RH
      mapping results showed that RBP95 is mapped to chromosome region 16p11.2-11.1.
      Sequence analysis indicated that RBP95 contains a conserved pRb-binding motif
      LXCXE. Interaction between pRb and RBP95 was confirmed in vivo and in vitro. This
      interaction requires the LXCXE motif of RBP95 and the entire pocket region of
      pRb. Each point-mutant of the conserved amino acid residues in pRb-binding motif
      of RBP95 would destroy its interaction with pRb. RBP95 also contains a basic
      region leucine zipper and could homodimerize through its leucine zipper region.
      RBP95 was located in the nucleus with a special pattern when expressed as a GFP
      fusion in HeLa cells. All these findings suggested that RBP95, a new member of
      pRb-associated protein, may function as a regulation factor in the process of RNA
      polymerase II-mediated transcription and/or transcriptional processing.

PMID- 10944456
TI  - Neuronal differentiation of PC12 cells involves changes in protein kinase C-theta
      distribution and molecular properties.
AB  - In this study we demonstrate that the rat pheochromocytoma PC12 cell line
      expresses the novel protein kinase C isozyme designated PKC-&theta;. The isozyme
      is almost completely localized in the nuclear compartment of proliferating cells.
      Following stimulation with the nerve growth factor, PKC-&theta; is redistributed
      into the cytoplasm and the outgrowing neurite processes, mostly as a cytoskeletal
      associated kinase. This event is accompanied by an eightfold increase in the
      expression level and by the appearance of specific modifications of PKC-&theta;
      molecule. Conversely, the kinase is down-regulated once cells reach the
      terminally differentiated state displaying a neuron-like phenotype. These data
      suggest a functional role for the kinase in the regulation of cytoskeletal
      modeling along the multistage differentiation process of PC12 cells.

PMID- 10944457
TI  - Homology modeling of human leptin/leptin receptor complex.
AB  - Leptin receptor mediates the weight regulatory signal carried by the adipocyte
      secreted peptide hormone, leptin. It is important to understand the atomic
      interactions between leptin and the receptor for the therapeutic applications.
      However, the structure of leptin receptor has not yet been determined. Leptin
      shows structural similarity to G-CSF, while leptin receptor is similar in amino
      acid sequence to G-CSF receptor. Because of the similarity between leptin/leptin
      receptor complex and G-CSF/G-CSF receptor complex, we tried to build a model
      structure of leptin/leptin receptor complex with the crystal structure of the G
      CSF/G-CSF receptor complex as the template. The obtained model for the complex
      was consistent with the results of the amino acid replacement and deletion
      experiments. The observation suggests that the model is useful to lead the
      experimental study on the interaction between leptin and the receptor.

PMID- 10944458
TI  - Expression of angiopoietin-2 by human endometrial endothelial cells: regulation
      by hypoxia and inflammation.
AB  - The functional endometrial layer receives the implanting blastocyst, but is
      sloughed off during menstruation. Angiogenesis regulates growth and repair of
      cycling human endometrium. While vascular endothelial growth factor initiates
      angiogenesis, the angiopoietins (Angs) acting via the Tie2 receptor, are key
      regulators of subsequent angiogenic steps. This study is the first to localize
      Ang-2 and Tie2 in human endometrium and to study Ang-2 regulation in cultured
      human endometrial endothelial cells (HEECs). Immunohistochemistry revealed that
      expression of Ang-2 and Tie2 was absent from the glands, low in stromal cells,
      and intense in the endothelial cells. In contrast, only weak expression of Ang-1
      was detected. The phase of the menstrual cycle did not appear to affect the
      expression of Ang-2 or Tie2. In vitro studies were carried out utilizing isolated
      HEECs, the most relevant model for endometrial microvascular biology studies.
      Both hypoxia and phorbol-myristate-acetate enhanced Ang-2 mRNA levels in HEECs.
      These results suggest that Ang-2 plays a role in endometrial pathologies
      complicated by impaired blood flow and inflammation.

PMID- 10944459
TI  - Intrathecal administration of neutralizing antibody against Fas ligand suppresses
      the progression of experimental autoimmune encephalomyelitis.
AB  - A therapy aimed at blocking the Fas/Fas ligand (FasL) system was investigated
      using a relapsing form of experimental autoimmune encephalomyelitis (EAE) in
      mice, an animal model of multiple sclerosis (MS). Intracisternal administration
      of neutralizing antibody against FasL during the progression phase of EAE
      significantly reduced the severity of the disease with milder inflammation and
      myelin breakdown in the central nervous system (CNS). These results raised the
      possibility that the Fas/FasL system might contribute to tissue destruction in
      the CNS in the acute phase of EAE and that the intrathecal administration of
      neutralizing antibody against FasL may be beneficial for suppression of the acute
      phase of MS.

PMID- 10944461
TI  - Extramitochondrial localization of mortalin/mthsp70/PBP74/GRP75.
AB  - Subcellular fractionation and immunofluorescence microscopy were used to identify
      the specific sites of intracellular residence of mortalin, also called a
      mitochondrial homologue of the hsp70 family, in immortal human cell lines
      previously assigned to four distinct complementation groups (A-D) for indefinite
      cell division. In addition to the mitochondria it was seen in the endoplasmic
      reticulum (ER) fractions of all the cell lines analyzed. Interestingly, three of
      the group A cells lines (EJ, GM639, and HT1080), in addition to the mitochondria
      and ER, exhibited cytosolically (extra-organelle) localized pool of mortalin.
      These findings demonstrate that mortalin is not present exclusively in
      mitochondria. Its residence in different organelles may be the basis of
      differential distribution observed previously in different human cell lines.

PMID- 10944460
TI  - Suppressive mechanism of salmosin, a novel disintegrin in B16 melanoma cell
      metastasis.
AB  - We have previously reported that salmosin, a novel disintegrin, was isolated from
      Korean snake (Agkistrodon halys brevicaudus) venom and significantly inhibited
      solid tumor growth in mice by perturbation of tumor-specific angiogenesis via
      blocking alphavbeta3 integrin expressed on vascular endothelial cells. In this
      study, we investigated the functional specificity of salmosin in tumor cell
      metastasis. Recombinant salmosin expressed in E. coli that has the RGD sequence
      markedly inhibited both B16F10 melanoma cell adhesion to the extracellular matrix
      proteins as well as B16F10 melanoma cell invasion through Matrigel-coated filter.
      The inhibition by salmosin can be caused by blocking integrins expressed on the
      surface of B16F10 melanoma cells. Salmosin significantly inhibited the
      proliferation of B16F10 melanoma cells on the plate coated with collagen I in a
      dose-dependent manner. In vivo B16F10 melanoma experimental metastasis, salmosin
      showed remarkable significant inhibitory effect on lung tumor colonization in a
      concentration-dependent manner. These results clearly demonstrate that
      antimetastatic activity of salmosin resulted from blocking the integrin-mediated
      adherence and alphavbeta3 integrin-mediated proliferation of the melanoma cells.

PMID- 10944462
TI  - Alternative exon usage of rat septins.
AB  - Septins represent a family of phylogenetically conserved proteins required for
      cytokinesis. Their presence in pre- and postsynaptic neuronal membranes suggests
      a general function as scaffolds for membrane reorganization. The transcriptional
      regulation of all septins examined so far is complex, resulting in alternatively
      spliced variants. We focus here on the rat homologue of the gene for the human
      septin MSF, a truncated form of which, designated eseptin, had been described
      previously. It will be shown here that there is an alternative usage of the first
      exon by two forms, named exon r1a and r1b, respectively. Exon r1a, but not exon
      r1b, contains a part of the coding sequence while the start of translation for
      the remaining coding sequence resides in the second exon. The complete genomic
      organization was resolved and data on the temporal and spatial expression of this
      septins are presented.

PMID- 10944463
TI  - Genomic organization and promoter analysis of mouse disabled 2 gene.
AB  - The mouse disabled 2 (mDab2) gene is a mouse homolog of the Drosophila disabled
      gene. It is markedly up regulated in retinoic acid (RA)-treated F9 cells,
      suggesting a role for mDab2 in the cell differentiation. To elucidate the
      molecular mechanisms that regulate RA-treated F9 cells specific expression of
      mDab2, we cloned and analyzed its genomic structure. The mDab2 gene spans over 55
      kilobases and has 13 exons. The transcription start site, mapped by primer
      extension and 5'RACE, was located at 53 base pairs (bp) upstream of the most 5'
      end of the published cDNA. Using reporter gene transfection analysis, we found
      that a 1-kb mDab2 5'-flanking sequence directed a high level of promoter activity
      in RA-treated F9 cells but not in untreated cells. Further deletion and mutation
      analyses identified a direct repeat of 5'-AGGAGGCGC-3' motif as novel positive
      regulatory element. Gel retardation assay showed that this element was needed to
      form specific DNA-protein complexes with factors present in RA-treated F9 cell
      extracts.

PMID- 10944464
TI  - Purification, identification, and cDNA cloning of Jun a 2, the second major
      allergen of mountain cedar pollen.
AB  - The second major allergen of Juniperus ashei (mountain cedar) pollen, Jun a 2,
      has been purified and its cDNA cloned. The purified protein has a molecular mass
      of 43 kDa and its N-terminal 9-residue amino acid sequence is highly homologous
      to those of Cry j 2 and Cha o 2, the second major allergen of Cryptomeria
      japonica and Chamaecyparis obtusa pollen, respectively. cDNA clones encoding Jun
      a 2 were isolated after PCR based amplification, and their nucleotide sequences
      were determined. The cDNA contains an open reading frame of 507 amino acid
      residues, and encodes a putative 54-residue signal sequence and a 453-residue
      intermediate, which releases a C-terminal fragment upon maturation. Three
      possible N-linked glycosylation sites and 20 cystein-residues are found in the
      deduced amino acid sequence. The amino acid sequence of Jun a 2 shows 70.7 and
      82.0% identity with those of Cry j 2 and Cha o 2, respectively. Immunological
      observations that IgE antibodies in sera of Japanese pollinosis patients bind not
      only to Cry j 2 and Cha o 2 but also to Jun a 2 strongly suggest that Jun a 2 is
      an allergen of mountain cedar pollen, and that allergenic epitopes of these three
      allergens are similar.

PMID- 10944465
TI  - The thyroid transcription factor 2 (TTF-2) is a promoter-specific DNA-binding
      independent transcriptional repressor.
AB  - The thyroid transcription factor TTF-2 is a forkhead-containing protein involved
      in thyroid-specific gene expression and necessary for thyroid morphogenesis. In
      this paper, we demonstrate that TTF-2 is able to inhibit the activity of the
      thyroid-specific transcription factors TTF-1 and Pax-8 only on certain promoters.
      We identified the minimal protein domain responsible for repressor activity,
      which behaves as an independent functional domain, and we show that repression by
      TTF-2 is DNA-binding independent. We suggest that TTF-2 is able to interfere with
      a specific cofactor required for TTF-1 and Pax-8 activity.

PMID- 10944466
TI  - Alternative splicing of the WNT-2B/WNT-13 gene.
AB  - Secreted glycoprotein WNTs play important roles in carcinogenesis and
      development. We have previously reported molecular cloning of WNT-2B/WNT-13.
      Here, we have isolated a novel WNT-2B isoform (WNT-2B2), in addition to the
      original WNT-2B isoform (WNT-2B1). WNT-2B1 and WNT-2B2 are completely different
      in the 5'-UTR and in the N-terminal part of the coding region. The N-terminal
      hydrophobic domain is contained in WNT-2B1, but not in WNT-2B2. WNT-2B1 and WNT
      2B2 share the WNT-core domain, and show 87.0% amino-acid identity. We have
      determined the structure of the WNT-2B gene. The WNT-2B1 mRNA consists of exons
      1, 2, and 4-7, while the WNT-2B2 mRNA consists of exons 3-7. WNT-2B2 was
      expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis,
      glioblastoma cell lines A172, SW1783, gastric cancer cell lines MKN28, MKN74, and
      cervical cancer cell line HeLa S3. WNT-2B1 expression level was relatively higher
      in fetal brain and fetal lung than in other tissues or cell lines expressing WNT
      2B2. These results indicate that the WNT-2B1 and WNT-2B2 mRNAs are transcribed
      due to alternative splicing with distinct expression profile. This is the first
      report on the WNT isoforms derived from the same gene due to alternative
      splicing.

PMID- 10944467
TI  - ILME: a waterborne pheromonal peptide released by the eggs of Sepia officinalis.
AB  - A novel tetrapeptide modulating the oviduct contractions was characterized from
      egg mass of Sepia officinalis. After two purification steps by rpHPLC, an
      apparent pure fraction containing the biological activity was submitted to MALDI
      TOF analysis. The mass spectrum revealed 6 peaks of m/z 293, 505, 596, 613, 728,
      and 745. The tissue peptide mapping performed in LC-MS demonstrated the
      occurrence of the m/z 505 peptide in the follicles, the full-grown oocytes, and
      in the eggs. This peptide was also recovered in the seawater after the incubation
      of full grown oocytes or eggs, demonstrating a release in the genital tract and
      in the environment. Edman degradation gave the following sequence: Ileu-Leu-Met
      Glu. The synthetic peptide applied to the whole genital tract triggered a
      cyclisation of the contractions at 10(-14) M. ILME appeared to be a chemical
      messenger released by the oocytes and the eggs, and was able to exert both
      paracrine and pheromonal activity.

PMID- 10944468
TI  - cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE
      regulated iron-responsive mRNAs.
AB  - Currently, the rapid amplification of cDNA ends (RACE) is the most common method
      for PCR cloning of cDNA. Because RACE uses a gene specific primer and one adaptor
      primer that is shared by all cDNAs may result in numerous nonspecific products
      that can hinder the cloning process. Here we report a new method that uses
      circularized first strand cDNA from mRNA and two gene specific primers to amplify
      both the 5' and 3' cDNA ends in one reaction. A cDNA band of correct size can be
      obtained on the first pass in this approach. If the correct size is not obtained
      on the first pass, amplification of cDNA ends can be repeated until the correct
      size of the cDNA is obtained. We tested this new method on eight mRNAs that we
      have previously shown to respond to cellular iron levels. We obtained sequences
      for six mRNAs that were 43 bp to 1324 bp longer than that reported in GenBank and
      obtained the same length sequence for the other two mRNAs. RNA folding program
      shows no iron responsive elements (IRE) on these mRNA. In conclusion, our cloning
      approach offers a more efficient method for cloning full-length cDNA and it may
      be used to replace the existing method of 5' end cDNA extension. The data enabled
      us to exclude the possibility that the expression of these iron responsive genes
      are regulated by IREs.

PMID- 10944469
TI  - Dbf4 motifs: conserved motifs in activation subunits for Cdc7 kinases essential
      for S-phase.
AB  - Dbf4 and its related molecules were originally identified as cyclin-like partners
      for Cdc7 kinases, essential for S-phase. Recent reports and database search
      indicate the presence of multiple Dbf4-related molecules with distinct functions.
      We have identified three stretches of amino acids which are conserved in various
      Dbf4-related molecules and possibly play distinct functions in binding to and
      activation of the catalytic subunits as well as in interactions with other
      proteins. Discovery of conserved motifs for this possible new protein family
      would serve as a useful framework for future identification of new members of
      this family as well as for probing their functions.

PMID- 10944470
TI  - Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.
AB  - Computer-based approaches identified PTE2 as a candidate human peroxisomal acyl
      CoA thioesterase gene. The PTE2 gene product is highly similar to the rat
      cytosolic and mitochondrial thioesterases, CTE1 and MTE1, respectively, and
      terminates in a tripeptide sequence, serine-lysine-valine(COOH), that resembles
      the consensus sequence for type-1 peroxisomal targeting signals. PTE2 was
      targeted to peroxisomes and recombinant PTE2 showed intrinsic acyl-CoA
      thioesterase activity with a pH optimum of 8.5. A comparison of PTE2 and PTE1
      thioesterase activities across multiple acyl-CoA substrates indicated that while
      PTE1 was most active on medium-chain acyl-CoAs, with little activity on long
      chain acyl-CoAs, PTE2 displayed high activity on medium- and long-chain acyl
      CoAs. The identification of PTE2 therefore offers an explanation for the observed
      long-chain acyl-CoA thioesterase activity of mammalian peroxisomes.

PMID- 10944471
TI  - Surface expression of lactoferrin by resting neutrophils.
AB  - We examined the surface expression of lactoferrin by human neutrophils. Western
      blot analysis with anti-lactoferrin antibodies demonstrated the presence of a 78-
      to 79-kDa band in plasma membranes isolated from resting neutrophils that
      corresponded to the 78- to 79-kDa protein in neutrophil secondary granules. Flow
      cytometry using FITC-conjugated anti-lactoferrin antibodies confirmed that
      lactoferrin is expressed on the neutrophil surface. Preincubating the neutrophils
      in acidic (pH 3.9) buffer did not alter staining of the cells by the antibodies.
      Surface expression of lactoferrin was also detected on neutrophils in whole
      blood. Neutrophil activation by C5a or the calcium ionophore A23187 did not
      increase the surface expression of lactoferrin. Instead, the level of lactoferrin
      expression detected with one of two monoclonal antibodies was diminished after
      neutrophil activation, suggesting a possible conformational change in the
      lactoferrin. The surface-expressed lactoferrin may provide a mechanism for the
      interaction between lactoferrin-binding microorganisms and neutrophils.

PMID- 10944472
TI  - The decay of linkage disequilibrium under random union of gametes: how to
      calculate Bennett's principal components.
AB  - How rapidly does an arbitrary pattern of statistical association among a set of
      loci decay under meiosis and random union of gametes? This problem is non
      trivial, even in the case of an infinitely large population where selection and
      other forces are absent. J. H. Bennett (1954, Ann. Hum. Genet. 18, 311-317) found
      that, for an arbitrary number of loci with an arbitrary linkage map, it is
      possible to define measures of linkage disequilibrium that decay geometrically
      with time. He found a recursive method for deriving expressions for these
      variables in terms of "allelic moments" (the factorial moments about the origin
      of the "allelic indicators"), and expressions for the allelic moments in terms of
      his new variables. However, Bennett no where stated his recursive algorithm
      explicitly, nor did he give a general formula for his measures of linkage
      disequilibrium, for an arbitrary number of loci. Recursive definitions of
      Bennett's variables were obtained by Lyubich. However, the expressions generated
      by these recursions are not the same as those found by Bennett. (They do not
      express Bennett's variables as functions of the allelic moments.) Lyubich's
      derivations employ genetic algebras. Here, I present a method for obtaining
      explicit expressions for Bennett's variables in terms of the allelic moments. I
      show that the transformation from the allelic moments to Bennett's variables and
      the inverse transformation always have the form that Bennett claimed. (This
      transformation and its inverse have essentially the same form.) I present general
      recursions for calculating the coefficients in the forward transformation and the
      coefficients in the inverse transformation. My derivations involve combinatorial
      arguments and ordinary algebra only. The special case of unlinked loci is briefly
      discussed.

PMID- 10944473
TI  - Simple stochastic models and their power-law type behaviour.
AB  - A power-law relationship between the mean and variance of ecological time series
      has been shown to hold for a vast number of species. Here we examine the
      behaviour of single-species stochastic models and concentrate in particular on
      the mean-variance relationship as the carrying capacity becomes large. Single
      species stochastic models can be written as Markov chains, and the long-term
      distribution of population sizes and hence power-law scaling can be found
      analytically. The various power-law scalings that arise have very different
      biological implications for the effects of stochasticity and the departure from
      the deterministic paradigm. Finally we extend our analysis to consider the
      complicating factors of spatial heterogeneity, nontrivial deterministic dynamics,
      and multispecies models.

PMID- 10944474
TI  - The ESS under spatial variation with applications to sex allocation.
AB  - I derive a new approximation which uses the backward Kolmogorov equation to
      describe evolution when individuals have variable numbers of offspring. This
      approximation is based on an explicit fixed population size assumption and
      therefore differs from previous models. I show that for individuals to accept an
      increase in the variance of offspring number, they must be compensated by an
      increase in mean offspring number. Based on this model and any given set of
      feasible alleles, an evolutionary stable strategy (ESS) can be found. Four types
      of ESS are possible and can be discriminated by graphical methods. These ESS
      values depend on population size, but population size can be reinterpreted as
      deme size in a structured population. I adapt this theory to the problem of sex
      allocation under variable returns to male and female function and derive the ESS
      sex allocation strategy. I show that allocation to the more variable sexual
      function should be reduced, but that this effect decreases as population size
      increases and as variability decreases. These results are compared with results
      from exact matrix models and computer simulations, all of which show strong
      congruence.

PMID- 10944475
TI  - Epistasis and the conversion of non-additive to additive genetic variance at
      population bottlenecks.
AB  - The effect of population bottlenecks on the mean and the additive variance
      generated by two neutral independent epistatic loci has been studied
      theoretically. Six epistatic models, used in the analysis of binary disease
      traits, were considered. Ancestral values in an infinitely large panmictic
      population were compared with their expectations at equilibrium, after t
      consecutive bottlenecks of equal size N (derived values). An increase in the
      additive variance after bottlenecks (inversely related to N and t) will occur
      only if the frequencies of the negative allele at each locus are: (1) low,
      invariably associated to strong inbreeding depression; (2) high, always
      accompanied by an enhancement of the mean with inbreeding. The latter is an
      undesirable property, making the pertinent models unsuitable for the genetic
      analysis of disease. For the epistatic models considered, it is unlikely that the
      rate of evolution may be accelerated after population bottlenecks, in spite of
      occasional increments of the derived additive variance over its ancestral value.

PMID- 10944476
TI  - On the genealogy of a sample of neutral rare alleles.
AB  - This paper concerns the genealogical structure of a sample of chromosomes sharing
      a neutral rare allele. We suppose that the mutation giving rise to the allele has
      only happened once in the history of the entire population, and that the allele
      is of known frequency q in the population. Within a coalescent framework C. Wiuf
      and P. Donnelly (1999, Theor. Popul. Biol. 56, 183-201) derived an exact analysis
      of the conditional genealogy but it is inconvenient for applications. Here, we
      develop an approximation to the exact distribution of the conditional genealogy,
      including an approximation to the distribution of the time at which the mutation
      arose. The approximations are accurate for frequencies q<5-10%. In addition, a
      simple and fast simulation scheme is constructed. We consider a demography
      parameterized by a d-dimensional vector alpha=(alpha(1), em leader, alpha(d)). It
      is shown that the conditional genealogy and the age of the mutation have
      distributions that depend on a=qalpha and q only, and that the effect of q is a
      linear scaling of times in the genealogy; if q is doubled, the lengths of all
      branches in the genealogy are doubled. The theory is exemplified in two different
      demographies of some interest in the study of human evolution: (1) a population
      of constant size and (2) a population of exponentially decreasing size (going
      backward in time).

PMID- 10944477
TI  - Micronutrients and infectious diseases: thoughts on integration of mechanistic
      approaches into micronutrient research.
AB  - Results of field and laboratory studies provide convincing evidence that
      micronutrient deficiencies contribute to the mortality and morbidity of
      infectious diseases. Despite encouraging results in large trials, understanding
      the mechanisms by which micronutrients contribute to the outcome of the encounter
      between an individual and an infectious agent requires additional hypothesis
      driven research. Presumably, such understanding should lead to translational
      studies with targeted nutritional therapy. Although these mechanistic studies are
      varied and complex, they must be done systematically and should include
      examination of the mechanisms by which micronutrients affect host-pathogen
      interactions, development of appropriate animal models and reliable methods for
      the assessment of micronutrient levels, and translation of the results of basic
      research findings into clinical studies. Moving the frontiers of micronutrient
      research from the laboratory to the field will be challenging. However, sound
      scientific research should lead toward better human health.

PMID- 10944478
TI  - Micronutrients and innate immunity.
AB  - Micronutrients such as zinc, selenium, iron, copper, beta-carotene, vitamins A,
      C, and E, and folic acid can influence several components of innate immunity.
      Select micronutrients play an important role in alteration of oxidant-mediated
      tissue injury, and phagocytic cells produce reactive oxidants as part of the
      defense against infectious agents. Thus, adequate micronutrients are required to
      prevent damage of cells participating in innate immunity. Deficiencies in zinc
      and vitamins A and D may reduce natural killer cell function, whereas
      supplemental zinc or vitamin C may enhance their activity. The specific effects
      of micronutrients on neutrophil functions are not clear. Select micronutrients
      may play a role in innate immunity associated with some disease processes. Future
      studies should focus on issues such as age-related micronutrient status and
      innate immunity, alterations of micronutrients in disease states and their effect
      on innate immunity, and the mechanisms by which micronutrients alter innate
      immunity.

PMID- 10944479
TI  - Effects of lycopene and lutein supplementation on the expression of functionally
      associated surface molecules on blood monocytes from healthy male nonsmokers.
AB  - It has been suggested that dietary carotenoids can enhance immune function.
      Supplementation with beta-carotene (15 mg daily) was previously shown to enhance
      human monocyte function. To examine the effect of other dietary carotenoids, two
      similar independent studies were done. Healthy adult male nonsmokers were
      randomly assigned to receive lycopene (study 1), lutein (study 2), or placebo for
      26 days, followed by the alternative treatment for another 26 days. The
      expression of functionally related monocyte surface molecules was quantified by
      laser flow cytometry before and after each treatment period. There was a
      significant increase in plasma levels of each carotenoid following dietary
      supplementation, but the effects on monocyte surface molecule expression were not
      as striking as those observed after beta-carotene supplementation. These findings
      emphasize that it cannot be assumed that the effect of one carotenoid will be the
      same as another, even at the same level of intake.

PMID- 10944480
TI  - Variations in the cell cycle status of lymphopoietic and myelopoietic cells
      created by zinc deficiency.
AB  - Zinc deficiency causes thymic atrophy and lymphopenia. It was recently shown that
      zinc deficiency causes sizable losses among the precursor lymphocytes, such that
      this compartment was depleted 40%-50% in the marrow of young adult mice. However,
      the myeloid compartments increased substantially both in proportion and absolute
      number as zinc deficiency advanced. Zinc deficiency caused no change in the cell
      cycle status of precursor B cells and only modest changes in cycling pro-B cells.
      Conversely, cells of the myeloid series, especially monocytes, exhibited as much
      as a 40% increase in the proportion of cells in S and G(2)/M, while myeloid
      progenitors had an overall 56% increase in cells in the proliferative phase as
      zinc deficiency advanced. Whether zinc deficiency alters the rate of production
      of myeloid and lymphopoietic cells or alters the degree of apoptosis or both
      awaits further study.

PMID- 10944481
TI  - Innate immunity, gut integrity, and vitamin A in Gambian and Indian infants.
AB  - Gut integrity, which can be measured by the urinary lactulose:mannitol excretion
      test, deteriorates with the introduction of weaning foods. In The Gambia, gut
      integrity measured monthly over 15 months in 119 infants (aged 2-15 months) was
      least impaired from April to June. This coincides with the time of year of
      maximum vitamin A (VA) intake-the mango season. Subsequently, two VA intervention
      studies were done in infants in India. Eighty infants attending a community
      health center received 16,700 IU weekly or placebo. In another study, 94
      hospitalized infants were given 200, 000 IU VA or placebo: 31 received VA on
      admission, while the rest (32 VA, 31 placebo) received treatment on discharge.
      All VA-treated groups had more rapid improvement in gut integrity than the
      placebo groups, but no group had gut integrity normalized by Western standards.
      The data suggest that VA status may influence gut integrity.

PMID- 10944482
TI  - Retinoic acid and polyriboinosinic acid act synergistically to enhance the
      antibody response to tetanus toxoid during vitamin A deficiency: possible
      involvement of interleukin-2 receptor-beta, signal transducer and activator of
      transcription-1, and interferon regulatory factor-1.
AB  - Antibody responses to T cell-dependent antigens are reduced during vitamin A (VA)
      deficiency and restored by retinoids. To test whether retinoic acid (RA) and
      polyinosinic:polycytidylic acid (PIC), an inducer of interferons, can increase
      specific antibody production, VA-deficient rats were treated with all-trans-RA,
      PIC, or both at the time of primary immunization with tetanus toxoid. VA
      deficient rats produced low primary and secondary anti-tetanus IgG responses
      (P<.001 vs. VA-sufficient controls). Both responses were increased
      synergistically by RA plus PIC (P<.0001). In VA-deficient spleens, mRNAs were low
      for interleukin (IL)-2 receptor-beta, interferon regulatory factor-1, and signal
      transducer and activator of transcription 1. Each, however, was induced by RA
      plus PIC (P<.0001 vs. controls). Conversely, IL-12 and IL-10 mRNAs were elevated
      in VA deficiency and were induced by PIC and suppressed by RA. Thus, RA plus PIC
      appears to be a promising combination for stimulating antigen-specific immunity.
      Several molecular factors identified here may partially account for the observed
      enhancement.

PMID- 10944483
TI  - Nutritional modulation of malaria morbidity and mortality.
AB  - This review critically examines the relationship between nutritional status and
      malaria. The data indicate that protein-energy malnutrition is associated with
      greater malaria morbidity and mortality in humans. In addition, controlled trials
      of either vitamin A or zinc supplementation show that these nutrients can
      substantially reduce clinical malaria attacks. Data for iron indicate that
      supplementation may minimally aggravate certain malariometric indices in some
      settings and also strongly improve hematologic status. Withholding of iron
      supplements from deficient population is, therefore, not currently indicated.
      Available evidence for other nutrients describe varied effects, with some
      deficiencies being exacerbative (e.g., thiamine), protective (e.g., vitamin E),
      or both exacerbative and protective in different settings (e.g., riboflavin,
      vitamin C). The roles of folate, other B vitamins, unsaturated fatty acids, amino
      acids, and selenium are also examined. Study of the interactions between
      nutrition and malaria may provide insight to protective mechanisms and result in
      nutrient-based interventions as low-cost and effective adjuncts to current
      methods of malaria prevention and treatment.

PMID- 10944484
TI  - Consumption of eicosapentaenoic acid and docosahexaenoic acid impair murine
      interleukin-12 and interferon-gamma production in vivo.
AB  - In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were
      found to be sufficient to effect the changes in circulating interleukin (IL)-12
      and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice.
      Weanling female C3H mice were fed one of five experimental diets. All five diets
      met all known nutritional requirements for mice and differed only in the fat
      source. After 4 weeks, mice were challenged with live Listeria monocytogenes or
      sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had
      significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control
      diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis
      factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing
      diets than in mice fed the olive oil ethyl esters control diet. The reduction of
      IL-12 and IFN-gamma production by n-3 PUFA may have important implications for
      host infectious disease resistance.

PMID- 10944486
TI  - Selenium and interleukins in persons infected with human immunodeficiency virus
      type 1.
AB  - An important role for selenium in human immunodeficiency virus (HIV) disease has
      been proposed. Decreased selenium levels, as found in persons with HIV infection
      or AIDS, are sensitive markers of disease progression. Selenium deficiency, an
      independent predictor of mortality in both HIV-1-infected adults and children, is
      an essential micronutrient that is associated with an improvement of T cell
      function and reduced apoptosis in animal models. In addition, adequate selenium
      may enhance resistance to infections through modulation of interleukin (IL)
      production and subsequently the Th1/Th2 response. Selenium supplementation up
      regulates IL-2 and increases activation, proliferation, differentiation, and
      programmed cell death of T helper cells. Moreover, selenium supplementation may
      down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha
      observed in HIV disease, which has been associated with neurologic damage,
      Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together,
      these findings suggest a new mechanism through which selenium may affect HIV-1
      disease progression.

PMID- 10944485
TI  - Effects of zinc deficiency on Th1 and Th2 cytokine shifts.
AB  - Nutritional deficiency of zinc is widespread throughout developing countries, and
      zinc-deficient persons have increased susceptibility to a variety of pathogens.
      Zinc deficiency in an experimental human model caused an imbalance between Th1
      and Th2 functions. Production of interferon-gamma and interleukin (IL)-2
      (products of Th1) were decreased, whereas production of IL-4, IL-6, and IL-10
      (products of Th2) were not affected during zinc deficiency. Zinc deficiency
      decreased natural killer cell lytic activity and percentage of precursors of
      cytolytic T cells. In HuT-78, a Th0 cell line, zinc deficiency decreased gene
      expression of thymidine kinase, delayed cell cycle, and decreased cell growth.
      Gene expression of IL-2 and IL-2 receptors (both alpha and beta) and binding of
      NF-kappaB to DNA were decreased by zinc deficiency in HuT-78. Decreased
      production of IL-2 in zinc deficiency may be due to decreased activation of NF
      kappaB and subsequent decreased gene expression of IL-2 and IL-2 receptors.

PMID- 10944487
TI  - Antioxidants, cytokines, and influenza infection in aged mice and elderly humans.
AB  - The age-associated dysregulation of the immune response contributes to higher
      incidences of infectious diseases in the aged. Of note, there is dysregulation of
      cytokines, including a change in T helper (Th) 1/Th2 cytokine balance and an
      increase in production of proinflammatory cytokines. Synthesis of many cytokines
      is influenced by changes in the cellular oxidant/antioxidant balance. Because
      vitamin E supplementation reduces oxidative stress and improves the immune
      response in the aged, a series of experiments was conducted to determine the
      effect of supplementation with vitamin E and other antioxidants on resistance to
      influenza infection in aged mice and the role of cytokines in vitamin E-induced
      increase in resistance to influenza infection. The results of these studies plus
      findings by other investigators on the effects of age and antioxidants on
      production of cytokines in human and animal models are reviewed.

PMID- 10944488
TI  - Regulation of cysteine-rich intestinal protein, a zinc finger protein, by
      mediators of the immune response.
AB  - Cysteine-rich intestinal protein (CRIP), a member of the LIM protein family, has
      a unique double zinc finger motif as the defining feature. CRIP is highly
      expressed in intestine and immune cells. CRIP transgenic (Tg) mice and
      nontransgenic controls were challenged with lipopolysaccharide (LPS). Serum
      concentrations of interferon-gamma and tumor necrosis factor-alpha were less
      while those of interleukin-6 and -10 were greater in the Tg mice following LPS
      administration. CRIP-overexpressing splenocytes produce the same cytokine
      profile. These responses are consistent with a regulatory role for this protein
      in cell differentiation, which produces an imbalance in Th1 and Th2 cytokines.
      Stimulation of CRIP protein levels by LPS is eliminated in metallothionein
      knockout mice, suggesting metallothionein is the source of zinc for this zinc
      finger protein and, further, that this could reflect a relationship to the zinc
      nutritional status and to the aberrant Th1/Th2 cytokine balance observed in zinc
      deficiency.

PMID- 10944489
TI  - Host nutritional status and its effect on a viral pathogen.
AB  - The nutritional status of the host has long been associated with both severity
      and susceptibility to infectious disease. The accepted model system proposes that
      inadequate nutrition impairs the functioning of the immune system, thus resulting
      in increased susceptibility to infection. However, current work suggests that not
      only can the nutritional status of the host affect the immune response, but it
      can also affect the viral pathogen. In a mouse model, a benign strain of
      coxsackievirus B3 became virulent and caused myocarditis in selenium- and vitamin
      E-deficient mice. This change in pathogenicity was due to mutations in the viral
      genome, which changed an avirulent virus into a virulent one. Once these
      mutations occurred, even mice with normal nutriture developed disease from the
      mutated virus. These results suggest that the oxidative stress status of the host
      can have a profound influence on a viral pathogen.

PMID- 10944490
TI  - Retinol and retinol-binding protein: gut integrity and circulating
      immunoglobulins.
AB  - Vitamin A (retinol) is required to maintain immunity and epithelial turnover and
      is a key micronutrient needed for combating infection. Vitamin A actions on the
      immune system are diverse and cannot be accounted for by a single effect or
      mechanism. The actions of retinol in maintaining gut integrity in humans and
      immunoglobulin levels in mice was investigated. For 30 children, performance on
      the lactulose/mannitol test, a test commonly used to assess intestinal barrier
      function, was inversely correlated (P=.012) with serum retinol concentrations.
      Thus, children with lower serum retinol, and presumably poorer vitamin A
      nutritional status, are more likely to have impaired intestinal integrity.
      Knockout mice that have impairments in plasma retinol transport have circulating
      immunoglobulin levels that are half those observed in matched wild type mice. No
      differences were observed in B and T cell populations present in spleen, thymus,
      and bone marrow.

PMID- 10944492
TI  - Phenotypic and functional considerations in the evaluation of immunity in
      nutritionally compromised hosts.
AB  - It is well established that proper nutrition is critical to the development of an
      effective immune system and to enhance the natural immunosurveillance and its
      effector mechanisms. This enhancement could be mediated either by increasing the
      frequency and absolute numbers of effector cells or by up-regulation of the
      cellular mechanisms by which these effector cells carry out their functions. Even
      in the Western world, large sectors of society often remain undernourished and
      show suboptimal immune responses, but the relationship between nutrition and
      immunity is best seen in developing and underdeveloped countries. Although there
      are many large-scale field studies that investigate the issue of nutrition and
      immunity, there are relatively few data that go beyond descriptive measurements
      and directly address how well the immune system functions. This review summarizes
      interactions between nutrition and immunity and focuses on practical aspects for
      evaluation of the immune function in the field.

PMID- 10944491
TI  - Effects of dietary n-3 fatty acids on T cell activation and T cell receptor
      mediated signaling in a murine model.
AB  - A short-term feeding paradigm in mice, with diets enriched with eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), was used to study the modulation of T
      cell activation via the T cell receptor (TcR) and the downstream pathways of
      intracellular signaling. Diets enriched in EPA and DHA suppressed antigen
      specific delayed hypersensitivity reactions and mitogen-induced proliferation of
      T cells. Cocultures of accessory cells and T cells from mice given different
      diets revealed that purified fatty acid ethyl esters acted directly on the T
      cell, rather than through the accessory cell. The loss of proliferative capacity
      was accompanied by reductions in interleukin (IL)-2 secretion and IL-2 receptor
      alpha chain mRNA transcription, suggesting that dietary EPA and DHA act, in part,
      by interrupting the autocrine IL-2 activation pathway. Dietary EPA and DHA
      blunted the production of intracellular second messengers, including
      diacylglycerol and ceramide, following mitogen stimulation in vitro. Dietary
      effects appear to vary with the agonist employed (i.e., anti-CD3 [TcR], anti
      CD28, exogenous IL-2, or phorbol myristate acetate and ionomycin).

PMID- 10944493
TI  - Effect of transfusional iron overload on immune response.
AB  - Increased susceptibility to infectious disease is observed in persons with
      transfusion-dependent thalassemia and iron overload who experience increased
      exposure to pathogens and chronic immune stimulation. An abnormal low CD8(+) T
      (LT8) immune phenotype defines a subgroup of patients. The CD8(+) T cell
      immunophenotype is stable despite continued blood transfusion and is independent
      of age. CD8(+) T cells, but not CD4(+) T cells, were modulated during intravenous
      chelation with deferoxamine. Return to characteristic pretreatment levels of CD8
      was observed in both the low and the normal groups, suggesting the possibility of
      a set point. Proliferative response to mitogens and antigens was increased by
      chelation. Because CD8(+) T cells are important in immune response to infectious
      disease, these studies suggest that intrinsic CD8(+) T cell subset differences
      may be a critical factor in determining susceptibility to infection independent
      of transfusional iron overload or alloantigen exposure.

PMID- 10944494
TI  - Vitamin A supplementation: implications for morbidity and mortality in children.
AB  - Vitamin A deficiency impairs epithelial integrity and systemic immunity and
      increases the incidence and severity of infections during childhood. However,
      findings from vitamin A supplementation trials are not consistent.
      Supplementation has resulted in significant reductions in mortality in several
      (but not all) large community-based trials among apparently healthy children. In
      hospital-based studies, vitamin A supplements have been consistently found to
      reduce the severity of measles infection, but no effect on nonmeasles respiratory
      infections has been observed. In some cases, the supplements were associated with
      an apparently increased risk of lower respiratory infection. Vitamin A
      supplements also reduced the severity of diarrhea in most (but not all) trials.
      Potential explanations for the differences in efficacy across trials are
      reviewed. While vitamin A supplementation is effective in reducing total
      mortality and complications from measles infections, it is likely to be more
      effective in populations suffering from nutritional deficiencies.

PMID- 10944495
TI  - Micronutrients and infection: interactions and implications with enteric and
      other infections and future priorities.
AB  - Symposium presentations have focused on the elegant molecular science and the
      biologic mechanisms by which micronutrients play critical roles in cellular and
      humoral immune responses, cellular signaling and function, and even in the
      evolution of microbial virulence. The concluding session examined the practical
      issues of how best to evaluate the nutritionally at-risk host, especially in the
      areas of greatest need-an analytical model of nutrient-immune interactions,
      implications of nutritional modulation of the immune response for disease, and
      the implications for international research and child health. This overview
      illustrated how malnutrition may be a major consequence of early childhood
      diarrhea and enteric infections, as enteric infections may critically impair
      intestinal absorptive function with potential long-term consequences for growth
      and development. The potentially huge, largely undefined DALY (disability
      adjusted life years) impact of early childhood diarrheal illnesses demonstrates
      the importance of quantifying the long-term functional impact of largely
      preventable nutritional and infectious diseases, especially in children in
      developing areas.

PMID- 10944496
TI  - The National Institutes of Health agenda for international research in
      micronutrient nutrition and infection interactions.
AB  - Nutrition is a central public health concern in the twenty-first century.
      Previous international research in nutrition was primarily descriptive
      epidemiology and included large-scale intervention trials. There has been
      insufficient attention to the mechanisms by which nutrient supplements appear to
      reduce mortality and little specificity in application and delineation of the
      forms of a specific nutrient to maximize benefits and minimize adverse affects
      and on the effect of nutrient combinations. After the dramatic success of the
      green revolution, agricultural research support was reduced despite an expanding
      world population and an increasing need for agricultural products. The potential
      of molecular genetics to improve food quality, specific nutrient content, and
      yield and disease resistance has just begun to be explored. In addition, the
      development of edible vaccines as a way to immunize a greater proportion of the
      world's children is a highly desirable goal and is achievable with sufficient
      resources.

PMID- 10944497
TI  - Action of calcitonin gene-related peptide (CGRP) and substance P on neurons in
      the insular cortex and the modulation of taste responses in the rat.
AB  - Using multibarrel electrodes, recordings were made from single neurons in the
      insular cortex including the cortical taste area (CTA) of urethane-anesthetized
      rats. The effects of an iontophoretic application of calcitonin gene-related
      peptide (CGRP) and substance P (SP) on the spontaneous discharges and taste
      responses were tested. In a total sample of neurons (mostly non-taste), CGRP
      affected the spontaneous discharges in 35.6% of the 571 neurons studied and SP in
      38.3% of the 775 neurons studied. The effects were mostly (approximately 85-87%)
      facilitatory. Peptide-sensitive neurons were found at a similar frequency in all
      three insular areas-granular, dysgranular and agranular (areas GI, DI and AI).
      This is in contrast to previous reports that CGRP receptors were rich in area DI
      and CGRP-immunoreactive afferents numerous in area AI, but consistent with
      previous reports that the distribution of SP receptors and SP fibers was dense in
      the insular cortex. In approximately 40% of the 76 taste neurons recorded from
      areas GI and DI, the peptides affected the spontaneous discharges (mostly
      facilitated). When the taste responses were examined during application of the
      peptides, significant (mainly depressant) effects were seen in 61% of 18 neurons
      for CGRP and in 70.5% of 17 for SP. Such effects were not recognized on responses
      to specific taste stimuli and were not correlated with the effects on the
      spontaneous discharges. The findings indicate that both peptides modify taste
      coding in CTA neurons presynaptically and/or postsynaptically, independently of
      the existence of receptors on the neurons.

PMID- 10944498
TI  - An In vitro assay useful to determine the potency of several bitter compounds.
AB  - Gustducin and transducin are guanine nucleotide binding regulatory proteins (G
      proteins) expressed in taste receptor cells and implicated in transducing taste
      cell responses to certain compounds that humans consider bitter or sweet. These G
      proteins can be activated in vitro by taste receptor-containing membranes plus
      any of several bitter compounds. This activation can be monitored using limited
      trypsin digestion, sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and immunoblotting. Scanning of the autoradiograms enables one to
      quantitate the level of activation (defined as an activation index), obtain dose
      response profiles and estimate the potency of the tastant. This assay may provide
      a useful substitute for, or adjunct to, the time-consuming human psychophysical
      analysis and costly animal studies typically used in taste sensory analysis. It
      may be used to identify and determine the concentration-response function of many
      bitter components of oral pharmaceuticals and food ingredients. A potential
      limitation of the assay is that only about half of all bitter compounds tested
      demonstrated in vitro activity, perhaps due to the presence of multiple
      transduction pathways. Nevertheless, the rapid throughput and microsample
      handling capability of this assay make it an ideal method to screen for high
      potency bitterness inhibitors.

PMID- 10944499
TI  - The vomeronasal cavity in adult humans.
AB  - We observed the surface of the anterior part of the nasal septum of living
      subjects using an endoscope. In approximately 13% of 1842 patients without
      pathology of the septum, the vomeronasal pit was clearly observed on each side of
      the septum, and in 26% it was observed only on one side. The remaining
      observations indicated either the presence of putative pits or no visible
      evidence of a pit. However, repetitive observations on 764 subjects depicted
      changes over time, from nothing visible to well-defined pits and vice versa.
      Based on 130 subjects observed at least four times, we estimate that
      approximately 73% of the population exhibits at least one clearly defined pit on
      some days. By computer tomography, the vomeronasal cavities were located at the
      base of the most anterior part of the nasal septum. Histological studies
      indicated that the vomeronasal cavities consisted of a pit generally connected to
      a duct extending in a posterior direction under the nasal mucosa. Many glands
      were present around the duct, which contained mucus. There was no sign of the
      pumping elements found in other mammalian species. Most cells in the vomeronasal
      epithelium expressed keratin, a protein not expressed by olfactory neurons.
      Vomeronasal epithelial cells were not stained by an antibody against the
      olfactory marker protein, a protein expressed in vomeronasal receptor neurons of
      other mammals. Moreover, an antibody against protein S100, expressed in Schwann
      cells, failed to reveal the existence of vomeronasal nerve bundles that would
      indicate a neural connection with the brain. Positive staining was obtained with
      the same antibodies on specimens of human olfactory epithelium. The lack of
      neurons and vomeronasal nerve bundles, together with the results of other
      studies, suggests that the vomeronasal epithelium, unlike in other mammals, is
      not a sensory organ in adult humans.

PMID- 10944500
TI  - Guanosine 3',5'-cyclic monophosphate reduces the response of the Moth's olfactory
      receptor neuron to pheromone.
AB  - The effects of the membrane-permeable dibutyryl guanosine 3', 5'-cyclic
      monophosphate (db-cGMP) on the bombykol-elicited receptor current and nerve
      impulse activity were studied using the open sensillum recording technique. db
      cGMP was applied to the outer dendritic membrane of the olfactory receptor neuron
      of the moth Bombyx mori. db-cGMP reduced the amplitude of the overall receptor
      current activated by a pulse of strong pheromone stimuli as well as diminished
      the nerve impulse frequency elicited by continuously applied weak pheromone
      stimuli. The observed inhibition of the response to pheromone was due to size
      reduction of an elementary receptor current that elicits the nerve impulses and
      underlies the overall receptor current. It is suggested that cGMP is a factor
      which may adjust cell sensitivity to odour and play a role in olfactory
      adaptation.

PMID- 10944501
TI  - Projection pattern of vomeronasal neurons to the accessory olfactory bulb in
      goats.
AB  - Goats have a well-developed vomeronasal (VN) system and exhibit pheromone-induced
      reproductive facilitation, but there are no reports on the projection pattern of
      VN neurons in this species. Rodent, guinea pig and opossum accessory olfactory
      bulbs (AOBs) have been shown to have a segregated pattern of projection of the VN
      neurons, which express the two alpha-subtypes of the G-protein, namely Gi2 and
      Go, to the rostral and caudal regions of the AOB, respectively. In this study we
      investigated the projection pattern of VN nerve terminals by immunocytochemical
      staining of the goat vomeronasal organ (VNO) and the AOB with antibodies to Gi2
      and Go. Gi2-immunoreactivity was found on the luminal surface of the sensory
      epithelium of the VNO, and in the VN nerve and glomerular layer throughout the
      AOB. On the other hand, Go-immunoreactivity was not identified in either the VNO
      or the VN nerve layer of the AOB. These results indicate that the projection
      pattern of VN neurons from the VNO to the AOB in the goat is considerably
      different from that in rodents which show a distinct segregated pattern.

PMID- 10944502
TI  - A controlled short-term exposure study to investigate the odor differences among
      three different formulations of gasoline.
AB  - Control subjects (CON) and self-reported methyl tertiary butyl ether (MTBE)
      sensitive subjects (SRS) were evaluated to distinguish between the following
      gasoline blends: gasoline versus gasoline + MTBE (15% MTBE v/v); and gasoline
      versus gasoline + MTBE + reodorant. The study also investigated the ability of a
      reodorant to conceal the odor of MTBE in a gasoline mixture. In each of two
      separate sessions, seven men (four CON, three SRS) and seven women (four CON,
      three SRS) were asked, in a forced-choice format, to sniff 28 randomized bottle
      pairs to determine if the odors in each pair were the same or different. Chi
      square analyses revealed that, with the exception of one male CON, subjects were
      unable to distinguish between gasoline and gasoline with MTBE or gasoline with
      MTBE and the reodorant. Thus, a reodorant is of limited value as an additive
      which alters the ability of an individual to detect MTBE in a blended gasoline.
      The results suggest that at the level used in the experiment, no mask would be
      required to blind a participant from the odor of MTBE if that level is used in a
      controlled human health effects study of the additive.

PMID- 10944503
TI  - Regional distribution of protein kinases in normal and odor-deprived mouse
      olfactory bulbs.
AB  - Unilateral naris closure produced dramatic down-regulation of tyrosine
      hydroxylase (TH) gene expression in periglomerular dopaminergic neurons in the
      olfactory bulb. To explore molecular mechanisms of TH gene regulation, the
      present study investigated the regional distribution of protein kinase A
      (PKAalpha), protein kinase C (PKCalpha), and CaM kinases II (CaMKIIalpha, beta)
      and IV (CaMKIV) in the normal olfactory bulb and in response to odor deprivation.
      Strong PKAalpha immunostaining was found in the glomerular, granule cell,
      external plexiform and olfactory nerve layers. PKCalpha staining was strong in
      granule cell and external plexiform layers but weak in the glomerular layer.
      Whereas CaMKIV was primarily found in granule cells, CaMKII was present in the
      glomerular, external plexiform, mitral cell and granule cell layers. No change in
      immunoreactivities of these kinases occurred in the olfactory bulb ipsilateral to
      naris closure. The expression of PKAalpha, PKCalpha and CaMKII, but not CaMKIV,
      in periglomerular cells suggests that these three kinases may play a role in TH
      gene regulation in the olfactory bulb. The lack of change in kinase protein
      levels after naris closure also suggests that any involvement of these kinases in
      TH gene expression in the olfactory bulb must be through altered kinase activity
      and not protein levels.

PMID- 10944504
TI  - Positive relationship between menstrual synchrony and ability to smell 5alpha
      androst-16-en-3alpha-ol.
AB  - To explore the possibility that compounds which were identified as pheromones in
      experimental animals mediate human menstrual synchrony, we examined the
      relationship between menstrual synchrony and the ability to smell putative
      pheromones, 5alpha-androst-16-en-3alpha-ol (3alpha-androstenol) and 5alpha
      androst-16-en-3-one (5alpha-androstenone). When we examined menstrual synchrony
      among 64 women living together in a college dormitory, we found that 24 (38%) of
      them became synchronized with room-mates in 3 months. Afterwards, dilution series
      of 3alpha-androstenol and 5alpha-androstenone and the control odorant (pyridine)
      were presented to the 64 women and sensitivity to the odors was compared between
      synchronized and non-synchronized women. No difference was found between the two
      groups of women in the detection threshold for pyridine, indicating that general
      olfactory ability did not differ between them. The detection threshold for 3alpha
      androstenol of synchronized women was significantly lower than that of non
      synchronized women, but no difference in the threshold for 5alpha-androstenone
      was found between synchronized and non-synchronized women. These results indicate
      that the women who showed menstrual synchrony had a higher sensitivity to 3alpha
      androstenol but not necessarily to 5alpha-androstenone.

PMID- 10944505
TI  - G protein betagamma complexes in circumvallate taste cells involved in bitter
      transduction.
AB  - G protein betagamma (Gbetagamma) complexes are considered to play an important
      role in second messenger signaling of phospholipase C (PLC). Monitoring the
      inositol 1,4,5-trisphosphate (IP(3)) response in circumvallate tissue homogenates
      upon stimulation with denatonium benzoate, it was demonstrated that a glutathione
      S-transferase-GRK3ct fusion protein-a Gbetagamma scavenger-attenuates the bitter
      tastant-induced second messenger reaction. Towards an identification of the
      Gbetagamma complex involved in rat bitter taste transduction, it was found that
      the G protein beta(3) subtype is specifically expressed in taste receptor cells
      of circumvallate papillae. Gbeta(3)-specific antibodies blocked the denatonium
      benzoate-induced IP(3) formation in a dose-dependent manner; the inhibitory
      effect was reversed by preincubation with the antigenic peptide. A less
      pronounced inhibition was observed using Gbeta(1)-specific antibodies. Analyzing
      individual taste cells by single cell reverse transcriptase-polymerase chain
      reaction approaches, overlapping expression patterns for PLCbeta(2),
      Galpha(gust), Gbeta(3) and Ggamma(3) could be demonstrated. Furthermore, the co
      expression of all profiled signal transduction components in individual taste
      receptor cells could be detected. These data support the concept that the
      denatonium benzoate-induced IP(3) response is mediated by an activation of
      PLCbeta(2) via a Gbetagamma complex, possibly composed of Gbeta(3) as the
      predominant beta subunit and Ggamma(3), and imply that multiple second messenger
      pathways may exist in individual taste receptor cells.

PMID- 10944506
TI  - Glossopharyngeal nerve transection does not alter taste reactivity to sucrose
      conditioned to be aversive.
AB  - Glossopharyngeal nerve (GL) transection in rats is known to markedly reduce
      gaping, a stereotypical aversive oromotor behavior, in response to intraorally
      delivered quinine. In this experiment we tested whether GL transection would
      reduce gaping in response to an otherwise palatable stimulus (sucrose) but
      conditioned to be aversive. Sprague-Dawley rats were implanted with intraoral
      cannulae. Five received bilateral transection of the GL and five served as sham
      operated controls. Water-deprived rats were presented with 0.3 M sucrose for 15
      min immediately followed by an injection of 0.15 M LiCl on three occasions. Rats
      were then habituated to the taste reactivity chamber and intraoral fluid infusion
      for 3 days, and tested on day 4 with a 1 ml infusion (1 min) of 0.3 M sucrose.
      All rats drank negligible amounts of sucrose by the third conditioning session
      and there were no differences in sucrose intake between the groups. There were no
      significant differences in gapes, or any other measured oromotor response, to
      sucrose between GL-transected and sham-operated rats. These results show that the
      GL is not a necessary afferent limb for gaping in response to conditionally
      aversive taste compounds.

PMID- 10944507
TI  - Quantification of odor quality.
AB  - The relationship between odor quality and molecular properties is arguably the
      most important issue in olfaction. Despite sophistication in the chemical
      characterization of molecules, accompanying perceptual characterization has had
      little quantitative usefulness, relying mostly on enumerative description. As a
      result of weak interest in the topic outside industry and little agreement
      regarding how to measure quality, the field of olfactory psychophysics has failed
      to develop a substantial database for odor quality and has offered little help to
      other researchers, e.g. neurobiologists, in choice of stimuli, interpretation of
      outcome or testable hypotheses. This review scrutinizes how psychophysicists and
      others have measured quality and offers criteria for useful techniques. Most
      measures have had a subjective component that makes them anachronistic with
      modern methodology in experimental behavioral science, indeterminate regarding
      the extent of individual differences, unusable with infrahumans and of unproved
      ability to discern small differences. Techniques based upon performance, rather
      than on the more common reporting of mental content, offer firmer possibilities
      for growth. These techniques inevitably tap the discriminative basis of
      perception. The nonsubjective techniques have high sensitivity, can have
      counterparts in infrahuman research, are suitable to examine individual
      differences and yield non-negotiable answers with potential archival value.
      Discriminative techniques have their limitations, too-principally excess
      sensitivity that abridges their use to comparisons between similar-smelling
      stimuli. Research has begun to extend that range and may overcome the limitation.
      Application of discriminative methods may have the side-effect of shifting focus
      in structure-activity research from searches for molecular least common
      denominators that underlie often vague similarity to the search for molecular
      properties of importance in discrimination of small differences.

PMID- 10944508
TI  - Introduction to review by linda bartoshuk

PMID- 10944510
TI  - Odor discrimination and task duration in young and older adults.
AB  - The effect of task duration on odor discrimination in aging was studied. Twenty
      seven young male adults and 24 young female adults between 18 and 30 years of
      age, and 17 older male adults between 45 and 65 years of age completed an odor
      discrimination task. The odor discrimination task consisted of two parts of 16
      trials each in which, from three bottles consisting of two identical and one
      aberrant odor, the aberrant odor had to be identified. The two parts were
      identical except that the aberrant odor was interchanged with the identical odors
      in the second as compared with the first part. Results revealed a decrease in
      odor discrimination with age. Moreover, with increased task duration odor
      discrimination performance decreased considerably in older male adults while it
      remained unchanged in young male adults. In addition, in young adults a small
      advantage in females as compared with males was found in the first part of the
      odor discrimination task, but this effect disappeared with increased task
      duration. In conclusion, task duration should be taken into consideration as a
      factor influencing odor discrimination in aging.

PMID- 10944512
TI  - Proceedings of the symposium on adaptation in vision and olfaction held at the
      XXI meeting of AChemS on april 15, 1999.

PMID- 10944511
TI  - Effects of 5alpha-androst-16-en-3alpha-ol on the pulsatile secretion of
      luteinizing hormone in human females.
AB  - We examined the effects of 5alpha-androst-16-en-3alpha-ol (3alpha-androstenol) on
      pulsatile luteinizing hormone (LH) secretion in human females. The frequency of
      the LH pulse in the follicular phase was decreased by exposing the women to
      3alpha-androstenol.

PMID- 10944509
TI  - Comparing sensory experiences across individuals: recent psychophysical advances
      illuminate genetic variation in taste perception.
AB  - Modern psychophysics has traveled considerably beyond the threshold measures that
      dominated sensory studies in the first half of this century. Current methods
      capture the range of perceived intensity from threshold to maximum and promise to
      provide increasingly accurate comparisons of perceived intensities across
      individuals. The application of new psychophysical tools to genetic variation in
      taste allowed us to discover supertasters, individuals who live in particularly
      intense taste worlds. Because of the anatomy of the taste system, supertasters
      feel more burn from oral irritants like chili peppers, more creaminess/ viscosity
      from fats and thickeners in food and may also experience more intense oral pain.
      Not surprisingly, these sensory differences influence food choices and thus
      health. A discussion of the milestones on the road to understanding genetic
      variation in taste must include discussion of some potholes as well. Often our
      failures have been as instructive as our successes in the effort to evaluate the
      impact of genetic variation in taste.

PMID- 10944513
TI  - The cellular and molecular basis of odor adaptation.
AB  - An important recent advance in the understanding of odor adaptation has come from
      the discovery that complex mechanisms of odor adaptation already take place at
      the earliest stage of the olfactory system, in the olfactory cilia. At least two
      rapid forms and one persistent form of odor adaptation coexist in vertebrate
      olfactory receptor neurons. These three different adaptation phenomena can be
      dissected on the basis of their different onset and recovery time courses and
      their pharmacological properties, indicating that they are controlled, at least
      in part, by separate molecular mechanisms. Evidence is provided for the
      involvement of distinct molecular steps in these forms of odor adaptation,
      including Ca(2+) entry through cyclic nucleotide-gated (CNG) channels, Ca(2+)
      dependent CNG channel modulation, Ca(2+)/calmodulin kinase II-dependent
      attenuation of adenylyl cyclase, and the activity of the carbon monoxide/cyclic
      GMP second messenger system. Identification of these molecular steps may help to
      elucidate how the olfactory system extracts temporal and intensity information
      and to which extent odor perception is influenced by the different mechanisms
      underlying adaptation.

PMID- 10944514
TI  - Adaptation-induced changes in sensitivity in frog olfactory receptor cells.
AB  - The suction pipette technique was used to study simultaneously the odour-induced
      action potential and receptor current responses in frog olfactory receptor cells,
      which were exposed to the odour cineole for 1 s by rapidly exchanging the
      solution bathing their cilia. The frequency of action potential firing increased
      as the odour concentration was raised and saturated within a 15-fold elevation
      above the odour threshold, while the number of spikes fired initially grew at low
      to-intermediate concentrations but then declined at higher concentrations. The
      receptor current response rose steadily and showed no clear sign of saturation
      over the 300-fold range of cineole concentration employed. The effect of
      adaptation on the sensitivity of olfactory receptor cells was investigated by
      first exposing the cell for 4 s to an adapting pre-pulse and then stimulating
      with a 1 s test pulse. As the pre-pulse concentration was increased, adaptation
      led to a progressive shift of the dose-response relationships towards higher test
      pulse concentrations. This resulted in a steep decline in the sensitivity of the
      receptor current response, combined with an even more dramatic fall in the
      sensitivity of the spiking responses, since the higher pre-pulse concentrations
      prevented the generation of action potentials at test pulse concentrations which
      still evoked a receptor current response.

PMID- 10944515
TI  - Psychophysical and behavioral characteristics of olfactory adaptation.
AB  - Sensory adaptation allows organisms to reach behavioral equilibrium with the
      ambient environment and respond primarily to changes in stimulation. Given its
      functional significance, it is not surprising that adaptation in the olfactory
      system exhibits many of the same characteristics as adaptation in other sensory
      systems, including vision. Repeated or prolonged exposure to an odorant typically
      leads to stimulus-specific decreases in olfactory sensitivity to that odorant,
      but sensitivity recovers over time in the absence of further exposure.
      Psychophysical analysis shows that olfactory adaptation results in elevations in
      odor thresholds and in reduced responsiveness to suprathreshold stimulation.
      Further, the magnitude of the decrease and the time course of adaptation and
      recovery are dependent on the concentration of the odor and on the duration of
      exposure. It is generally agreed that olfactory adaptation can occur at multiple
      levels in the olfactory system and can involve both peripheral (receptor level)
      and more central (post-receptor) components. Evidence for peripheral and central
      involvement comes from studies showing that monorhinal stimulation results in
      adaptation in both the ipsilateral and contralateral nostril, although the degree
      of adaptation in the ipsilateral nostril is more profound and recovery is slower.
      Additional evidence for central involvement comes from studies that have found
      relatively small decreases in peripheral response following repeated stimulation
      despite substantial reductions in perceived intensity. Most psychophysical
      studies of adaptation, however, have not differentiated the peripheral and
      central processes. Although relatively few in number, studies of the parametric
      features of olfactory adaptation in both vertebrate (e.g. rat) and invertebrate
      (e.g. Drosophila, Caenorhabditis elegans) animal models appear to replicate the
      findings in psychophysical studies of adult humans. Despite the broad overall
      similarity of olfactory adaptation to adaptation in other sensory systems,
      olfactory adaptation exhibits some unique features. Adaptation in olfaction has
      been shown to be very long-lasting in some cases and may be modulated by the
      contribution of pre-neural events and physico-chemical properties of the odorant
      molecules that govern diffusion to receptor sites and post-receptor clearance.

PMID- 10944516
TI  - Ligand type-specific interactions of peroxisome proliferator-activated receptor
      gamma with transcriptional coactivators.
AB  - The nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      member of the nuclear receptor superfamily and acts as a ligand-dependent
      transcription factor mediating adipocyte differentiation, cell proliferation and
      inflammatory processes, and modulation of insulin sensitivity. Members of the 160
      kDa protein (SRC-1/TIF2/AIB-1) family of coactivators, CBP/p300 and
      TRAP220/DRIP205, are shown to interact directly with PPARgamma and potentiate
      nuclear receptor transactivation function in a ligand-dependent fashion. Because
      PPARgamma ligands exert partially overlapping but distinct subsets of biological
      action through PPARgamma binding, we wished to examine whether interactions
      between PPARgamma and known coactivators were induced to the same extent by
      different classes of PPARgamma ligand. The natural ligand 15-deoxy-Delta12,14
      prostaglandin J(2) induced PPARgamma interactions with all coactivators tested
      (SRC-1, TIF2, AIB-1, p300, TRAP220/DRIP205) in yeast and mammalian two-hybrid
      assays, as well as in a glutathione S-transferase pull-down assay. However, under
      the same conditions troglitazone, a synthetic PPARgamma ligand that acts as an
      antidiabetic agent, did not induce PPARgamma interactions with any of the
      coactivators. Our findings suggest that ligand binding may alter PPARgamma
      structure in a ligand type-specific way, resulting in distinct PPARgamma
      coactivator interactions.

PMID- 10944517
TI  - Identification of sequence determinants that direct different intracellular
      folding pathways for aquaporin-1 and aquaporin-4.
AB  - Homologous aquaporin water channels utilize different folding pathways to acquire
      their transmembrane (TM) topology in the endoplasmic reticulum (ER). AQP4
      acquires each of its six TM segments via cotranslational translocation events,
      whereas AQP1 is initially synthesized with four TM segments and subsequently
      converted into a six membrane-spanning topology. To identify sequence
      determinants responsible for these pathways, peptide segments from AQP1 and AQP4
      were systematically exchanged. Chimeric proteins were then truncated, fused to a
      C-terminal translocation reporter, and topology was analyzed by protease
      accessibility. In each chimeric context, TM1 initiated ER targeting and
      translocation. However, AQP4-TM2 cotranslationally terminated translocation,
      while AQP1-TM2 failed to terminate translocation and passed into the ER lumen.
      This difference in stop transfer activity was due to two residues that altered
      both the length and hydrophobicity of TM2 (Asn(49) and Lys(51) in AQP1 versus
      Met(48) and Leu(50) in AQP4). A second peptide region was identified within the
      TM3-4 peptide loop that enabled AQP4-TM3 but not AQP1-TM3 to reinitiate
      translocation and cotranslationally span the membrane. Based on these findings,
      it was possible to convert AQP1 into a cotranslational biogenesis mode similar to
      that of AQP4 by substituting just two peptide regions at the N terminus of TM2
      and the C terminus of TM3. Interestingly, each of these substitutions disrupted
      water channel activity. These data thus establish the structural basis for
      different AQP folding pathways and provide evidence that variations in
      cotranslational folding enable polytopic proteins to acquire and/or maintain
      primary sequence determinants necessary for function.

PMID- 10944518
TI  - The first selective agonist for the neuropeptide YY5 receptor increases food
      intake in rats.
AB  - The first Y(5) receptor-selective analog of neuropeptide Y (NPY),
      [Ala(31),Aib(32)]NPY, has been developed and biologically characterized. Using
      competition binding assays on cell lines that express different Y receptors, we
      determined the affinity of this analog to be 6 nm at the human Y(5) receptor,
      >500 nm at the Y(1) and Y(2) receptors, and >1000 nm at the Y(4) receptor.
      Activity studies performed in vitro using a cAMP enzyme immunoassay, and in vivo
      using food intake studies in rats, showed that the peptide acted as an agonist.
      Further peptides obtained by the combination of the Ala(31)-Aib(32) motif with
      chimeric peptides containing segments of NPY and pancreatic polypeptide displayed
      the same selectivity and even higher affinity (up to 0.2 nm) for the Y(5)
      receptor. In vivo administration of the new Y(5) receptor-selective agonists
      significantly stimulated feeding in rats. The NMR solution structures of NPY and
      [Ala(31),Aib(32)]NPY showed a different conformation in the C-terminal region,
      where the alpha-helix of NPY was substituted by a more flexible, 3(10)-helical
      turn structure.

PMID- 10944519
TI  - Inhibition of selectin-mediated cell adhesion and prevention of acute
      inflammation by nonanticoagulant sulfated saccharides. Studies with carboxyl
      reduced and sulfated heparin and with trestatin a sulfate.
AB  - Selectins play a major role in the inflammatory reaction by initiating neutrophil
      attachment to activated vascular endothelium. Some heparin preparations can
      interact with L- and P-selectin; however, the determinants required for
      inhibiting selectin-mediated cell adhesion have not yet been characterized. We
      now report that carboxyl-reduced and sulfated heparin (prepared by chemical
      modifications of porcine intestinal mucosal heparin leading to the replacement of
      carboxylates by O-sulfate groups) and trestatin A sulfate (obtained by sulfation
      of trestatin A, a non-uronic pseudo-nonasaccharide extracted from Streptomyces
      dimorphogenes) exhibit strong anti-P-selectin and anti-L-selectin activity while
      lacking antithrombin-mediated anticoagulant activity. In vitro experiments
      revealed that both compounds inhibited P-selectin- and L-selectin-mediated cell
      adhesion under laminar flow conditions. Moreover, carboxyl-reduced and sulfated
      heparin and trestatin A sulfate were also active in vivo, as assessed by
      experiments showing 1) that microinfusion of trestatin A sulfate reduced by 96%
      leukocyte rolling along rat mesenteric postcapillary venules and 2) that both
      compounds inhibited (by 58-81%) neutrophil migration into thioglycollate-inflamed
      peritoneum of BALB/c mice. These results indicate that nonanticoagulant sulfated
      saccharides targeted at P-selectin and L-selectin may have therapeutic potential
      in inflammatory disorders.

PMID- 10944521
TI  - Characterization of METH-1/ADAMTS1 processing reveals two distinct active forms.
AB  - METH-1/ADAMTS1 is a member of a newly described family of genes that contain
      metalloprotease, disintegrin, and thrombospondin-like motifs. We have recently
      shown that METH-1 protein is a potent inhibitor of angiogenesis. Here, we
      demonstrate that secreted human pro-METH-1 is processed in two consecutive steps
      to release both p87 and p65 active forms. The p87 form lacks the N-terminal
      prodomain and p65 results from an additional processing event in the C-terminal
      end. Generation of p87 was blocked with specific inhibitors of furin, and
      incubation of pro-METH-1 with purified furin released the p87 fragment but not
      p65. Generation of p65 required preformation of p87 and was suppressed by
      inhibitors of matrix metalloproteases. We demonstrate that matrix
      metalloproteases 2, 8, and 15 were able to release p65 when p87 was used as
      substrate. This second processing step removes two thrombospondin repeats from
      the carboxyl-terminal end of p87-METH-1 and alters the affinity of the protein to
      heparin and endothelial cultures. Furthermore, this deletion was associated with
      a reduced activity upon suppression of endothelial cell proliferation. We
      hypothesize that METH-1 processing is relevant for the modulation of the anti
      angiogenic properties displayed by the protein.

PMID- 10944520
TI  - RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15
      disintegrin domains mediates cell-cell interaction.
AB  - ADAMs (a disintegrin and metalloproteases) mediate several important processes
      (e.g. tumor necrosis factor-alpha release, fertilization, and myoblast fusion).
      The ADAM disintegrin domains generally lack RGD motifs, and their receptors are
      virtually unknown. Here we show that integrin alpha(9)beta(1) specifically
      interacts with the recombinant ADAMs-12 and -15 disintegrin domains in an RGD
      independent manner. We also show that interaction between ADAM-12 or -15 and
      alpha(9)beta(1) supports cell-cell interaction. Interestingly, the cation
      requirement and integrin activation status required for alpha(9)beta(1)/ADAM
      mediated cell adhesion and cell-cell interaction is similar to those required for
      known integrin-extracellular matrix interaction. These results are quite
      different from recent reports that ADAM-2/alpha(6)beta(1) interaction during
      sperm/egg fusion requires an integrin activation status distinct from that for
      extracellular matrix interaction. These results suggest that alpha(9)beta(1) may
      be a major receptor for ADAMs that lack RGD motifs, and that, considering a wide
      distribution of ADAMs and alpha(9)beta(1), this interaction may be of potential
      biological and pathological significance.

PMID- 10944522
TI  - Effects of the regulatory light chain phosphorylation of myosin II on mitosis and
      cytokinesis of mammalian cells.
AB  - Myosin plays an important role in mitosis, especially during cytokinesis.
      Although it has been assumed that phosphorylation of regulatory light chain of
      myosin (RLC) controls motility of mammalian non-muscle cells, the functional
      significance of RLC phosphorylation remains uninvestigated. To address this
      problem, we have produced unphosphorylatable RLC (T18A/S19A RLC) and
      overexpressed it in COS-7 cells and normal rat kidney cells. Overexpression of
      T18A/S19A RLC but not wild type RLC almost completely abolished concanavalin A
      induced receptor cap formation. The results indicate that myosin phosphorylation
      is critical for concanavalin A-induced gathering of surface receptors. T18A/S19A
      RLC overexpression resulted in the production of multinucleated cells, suggesting
      the failure of proper cell division in these cells. Video microscopic observation
      revealed that cells expressing T18A/S19A RLC showed abnormalities during mitosis
      in two respects. One is that the cells produced abnormal cleavage furrows,
      resulting in incomplete cytokinesis, which suggests that myosin phosphorylation
      is important for the normal recruitment of myosin molecules into the contractile
      ring structure. The other is that separation of chromosomes from the metaphase
      plate is disrupted in T18A/S19A RLC expressing cells, thus preventing proper
      transition from metaphase to anaphase. These results suggest that, in addition to
      cytokinesis, myosin and myosin phosphorylation play a role in the karyokinetic
      process.

PMID- 10944523
TI  - Involvement of gangliosides in glycosylphosphatidylinositol-anchored neuronal
      cell adhesion molecule TAG-1 signaling in lipid rafts.
AB  - The association of ganglioside GD3 with TAG-1, a glycosylphosphatidylinositol
      anchored neuronal cell adhesion molecule, was examined by coimmunoprecipitation
      experiments. Previously, we have shown that the anti-ganglioside GD3 antibody
      (R24) immunoprecipitated the Src family kinase Lyn from the rat cerebellum, and
      R24 treatment of primary cerebellar cultures induced Lyn activation and rapid
      tyrosine phosphorylation of an 80-kDa protein (p80). We now report that R24
      coimmunoprecipitates a 135-kDa protein (p135) from primary cerebellar cultures.
      Treatment with phosphatidylinositol-specific phospholipase C revealed that p135
      was glycosylphosphatidylinositol-anchored to the membrane. It was identified as
      TAG-1 by sequential immunoprecipitation with an anti-TAG-1 antibody. Antibody
      mediated cross-linking of TAG-1 induced Lyn activation and rapid tyrosine
      phosphorylation of p80. Selective inhibitor for Src family kinases reduced the
      tyrosine phosphorylation of p80. Sucrose density gradient analysis revealed that
      the TAG-1 and tyrosine-phosphorylated p80 in cerebellar cultures were present in
      the lipid raft fraction. These data show that TAG-1 transduces signals via Lyn to
      p80 in the lipid rafts of the cerebellum. Furthermore, degradation of cell
      surface glycosphingolipids by endoglycoceramidase induced an alteration of TAG-1
      distribution on an OptiPrep gradient and reduced the TAG-1-mediated Lyn
      activation and tyrosine phosphorylation of p80. These observations suggest that
      glycosphingolipids are involved in TAG-1-mediated signaling in lipid rafts.

PMID- 10944524
TI  - Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and
      angiogenesis by integrin alpha5beta1 and protein kinase A.
AB  - Recent studies indicate that angiogenesis depends, in part, on ligation of
      integrin alpha(5)beta(1) by fibronectin. Evidence is now provided that integrin
      alpha(5)beta(1) regulates the function of integrin alpha(v)beta(3) on endothelial
      cells during their migration in vitro or angiogenesis in vivo. Secretion of
      fibronectin by endothelial cells leads to the ligation of integrin
      alpha(5)beta(1), which potentiates alpha(v)beta(3)-mediated migration on
      vitronectin without influencing alpha(v)beta(3)-mediated cell adhesion.
      Endothelial cell attachment to vitronectin suppresses protein kinase A (PKA)
      activity, while addition of soluble anti-alpha(5)beta(1) restores this activity.
      Moreover, agents that activate intracellular PKA, such as forskolin, dibutyryl
      cAMP or alpha(5)beta(1) antagonists, suppress endothelial cell migration on
      vitronectin in vitro or angiogenesis in vivo. In contrast, inhibitors of PKA
      reverse the anti-migratory or anti-angiogenic effects mediated by alpha(5)beta(1)
      antagonists. Therefore, alpha(v)beta(3)-mediated endothelial cell migration and
      angiogenesis can be regulated by PKA activity, which depends on the ligation
      state of integrin alpha(5)beta(1).

PMID- 10944525
TI  - Heregulin-dependent trafficking and cleavage of ErbB-4.
AB  - Heregulin was shown to promote the proteolytic cleavage of its receptor, ErbB-4,
      in several cell lines. The growth factor also rapidly promoted the transient
      translocation of ErbB-4 to a detergent-insoluble fraction, in which the receptor
      was hyper-tyrosine-phosphorylated compared with the receptor present in the
      detergent-soluble pool. However, an 80-kDa proteolytic fragment of ErbB-4 was
      found in the detergent-soluble fraction, but not in the detergent-insoluble
      fraction. Although the heregulin-induced cleavage of ErbB-4 produced a fragment
      of ErbB-4 very similar to that induced by 12-O-tetradecanoylphorbol-13-acetate or
      pervanadate (each of which is blocked by metalloprotease inhibitors), the growth
      factor-induced cleavage was not sensitive to these inhibitors under the same
      conditions. The heregulin-induced cleavage of ErbB-4 could be blocked by
      conditions that prevent clathrin-coated pit formation, suggesting that heregulin
      mediated ErbB-4 cleavage occurs subsequent to internalization. When reagents that
      prevent acidification of endosomes were employed, heregulin-induced ErbB-4
      cleavage was sensitive to metalloprotease inhibitors. The results imply that
      during ligand-dependent receptor trafficking, activated ErbB-4 receptors are
      subject to proteolytic cleavage involving an intracellular metalloprotease.

PMID- 10944527
TI  - Characterization of the promoter of human leukocyte-specific transcript 1. A
      small gene with a complex pattern of alternative transcripts.
AB  - The gene for the human leukocyte-specific transcript 1 (LST1) encodes a small
      protein that modulates immune responses and cellular morphogenesis. The LST1
      transcripts are expressed at high levels in dendritic cells. Because of the
      complex splicing pattern, use of alternative 5'-untranslated exons, and a
      biologically interesting pattern of expression of LST1 mRNA, we studied the human
      LST1 gene promoter and regulatory elements. We identified an additional upstream
      5'-untranslated exon in U937 monocytic cells. Transient transfection studies
      demonstrated that the combination of regions from -1363 to -621 with -112 to -54,
      relative to the translation start codon, produced the highest level of
      transcripts from among the various constructs tested, but the pattern of
      transcripts produced was only a subset of those produced from the endogenous
      gene. DNase I footprinting analysis and electrophoretic mobility shift assays
      showed that oligonucleotide probes corresponding to three regions, -1171 to -1142
      (BI), -1136 to -1111 (BII), and -783 to -751 (BIV), bound proteins in U937
      nuclear extracts. Competition and supershift electrophoretic mobility shift assay
      did not identify any known transcription factors responsible for BII probe
      binding. These studies suggest that a novel DNA-binding site and interaction of
      multiple regulatory elements may be involved in mediating the expression of the
      various forms of LST1 mRNA.

PMID- 10944526
TI  - CREB-binding protein/p300 activates MyoD by acetylation.
AB  - The myogenic protein MyoD requires two nuclear histone acetyltransferases, CREB
      binding protein (CBP)/p300 and PCAF, to transactivate muscle promoters. MyoD is
      acetylated by PCAF in vitro, which seems to increase its affinity for DNA. We
      here show that MyoD is constitutively acetylated in muscle cells. In vitro, MyoD
      is acetylated both by CBP/p300 and by PCAF on two lysines located at the boundary
      of the DNA binding domain. MyoD acetylation by CBP/p300 (as well as by PCAF)
      increases its activity on a muscle-specific promoter, as assessed by
      microinjection experiments. MyoD mutants that cannot be acetylated in vitro are
      not activated in the functional assay. Our results provide direct evidence that
      MyoD acetylation functionally activates the protein and show that both PCAF and
      CBP/p300 are candidate enzymes for MyoD acetylation in vivo.

PMID- 10944528
TI  - Expression, purification, and characterization of gp160e, the soluble, trimeric
      ectodomain of the simian immunodeficiency virus envelope glycoprotein, gp160.
AB  - The envelope glycoprotein, gp160, of simian immunodeficiency virus (SIV) shares
      approximately 25% sequence identity with gp160 from the human immunodeficiency
      virus, type I, indicating a close structural similarity. As a result of binding
      to cell surface CD4 and co-receptor (e.g. CCR5 and CXCR4), both SIV and human
      immunodeficiency virus gp160 mediate viral entry by membrane fusion. We report
      here the characterization of gp160e, the soluble ectodomain of SIV gp160. The
      ectodomain has been expressed in both insect cells and Chinese hamster ovary
      (CHO)-Lec3.2.8.1 cells, deficient in enzymes necessary for synthesizing complex
      oligosaccharides. Both the primary and a secondary proteolytic cleavage sites
      between the gp120 and gp41 subunits of gp160 were mutated to prevent cleavage and
      shedding of gp120. The purified, soluble glycoprotein is shown to be trimeric by
      chemical cross-linking, gel filtration chromatography, and analytical
      ultracentrifugation. It forms soluble, tight complexes with soluble CD4 and a
      number of Fab fragments from neutralizing monoclonal antibodies. Soluble
      complexes were also produced of enzymatically deglycosylated gp160e and of gp160e
      variants with deletions in the variable segments.

PMID- 10944529
TI  - XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled
      DNA repair and transcription.
AB  - Nucleotide excision repair is a highly versatile DNA repair system responsible
      for elimination of a wide variety of lesions from the genome. It is comprised of
      two subpathways: transcription-coupled repair that accomplishes efficient removal
      of damage blocking transcription and global genome repair. Recently, the basic
      mechanism of global genome repair has emerged from biochemical studies. However,
      little is known about transcription-coupled repair in eukaryotes. Here we report
      the identification of a novel protein designated XAB2 (XPA-binding protein 2)
      that was identified by virtue of its ability to interact with XPA, a factor
      central to both nucleotide excision repair subpathways. The XAB2 protein of 855
      amino acids consists mainly of 15 tetratricopeptide repeats. In addition to
      interacting with XPA, immunoprecipitation experiments demonstrated that a
      fraction of XAB2 is able to interact with the transcription-coupled repair
      specific proteins CSA and CSB as well as RNA polymerase II. Furthermore,
      antibodies against XAB2 inhibited both transcription-coupled repair and
      transcription in vivo but not global genome repair when microinjected into living
      fibroblasts. These results indicate that XAB2 is a novel component involved in
      transcription-coupled repair and transcription.

PMID- 10944531
TI  - Apolipoprotein A-I regulates lipid hydrolysis by hepatic lipase.
AB  - Association of hepatic lipase (HL) with pure heparan sulfate proteoglycans (HSPG)
      has little effect on hydrolysis of high density lipoprotein (HDL) particles, but
      significantly inhibits (>80%) the hydrolysis of low (LDL) and very low density
      lipoproteins (VLDL). Lipolytic inhibition is associated with a differential
      ability of the lipoproteins to remove HL from the HSPG. LDL and VLDL are unable
      to displace HL, whereas HDL readily displaces HL from the HSPG. These data show
      that HSPG-bound HL is inactive. Purified apolipoprotein (apo) A-I is more
      efficient than HDL at liberating HL from HSPG, and HL displacement is associated
      with the direct binding of apoA-I to HSPG. However, displacement of HL by apoA-I
      does not enhance hydrolysis of VLDL particles. This appears due to the direct
      inhibition of HL by apoA-I. Both apoA-I and HDL are able to inhibit VLDL lipid
      hydrolysis by up to 60%. Inhibition of VLDL hydrolysis is associated with the
      binding of apoA-I to the surface of the VLDL particle and a concomitant decreased
      affinity for HL. These data show that apoA-I can regulate lipid hydrolysis by HL
      by liberating/activating the enzyme from cell surface proteoglycans and by
      directly modulating lipoprotein binding and hydrolysis.

PMID- 10944530
TI  - Permeabilization via the P2X7 purinoreceptor reveals the presence of a Ca2+
      activated Cl- conductance in the apical membrane of murine tracheal epithelial
      cells.
AB  - Calcium-activated Cl(-) secretion is an important modulator of regulated ion
      transport in murine airway epithelium and is mediated by an unidentified Ca(2+)
      stimulated Cl(-) channel. We have transfected immortalized murine tracheal
      epithelial cells with the cDNA encoding the permeabilizing P2X(7) purinoreceptor
      (P2X(7)-R) to selectively permeabilize the basolateral membrane and thereby
      isolate the apical membrane Ca(2+)-activated Cl(-) current. In P2X(7)-R
      permeabilized cells, we have demonstrated that UTP stimulates a Cl(-) current
      across the apical membrane of CF and normal murine tracheal epithelial cells. The
      magnitude of the UTP-stimulated current was significantly greater in CF than in
      normal cells. Ion substitution studies demonstrated that the current exhibited a
      permselectivity sequence of Cl(-) > I(-) > Br(-) > gluconate(-). We have also
      determined a rank order of potency for putative Cl(-) channel blockers: niflumic
      acid > or = 5-nitro-2-(3-phenylpropylamino)benzoic acid > 4, 4'
      diisothiocyanostilbene-2,2'-disulfonate > glybenclamide >> diphenlyamine-2
      carboxylate, tamoxifen, and p-tetra-sulfonato-tetra-methoxy-calix[4]arene.
      Complete characterization of this current and the corresponding single channel
      properties could lead to the development of a new therapy to correct the
      defective airway surface liquid in cystic fibrosis patients.

PMID- 10944532
TI  - Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB
      degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts.
AB  - Fibroblast growth factor-2 (FGF-2) interacts with a dual receptor system
      consisting of tyrosine kinase receptors and heparan sulfate proteoglycans
      (HSPGs). In rat mammary fibroblasts, FGF-2 stimulated DNA synthesis and induced a
      sustained phosphorylation of p42/44(MAPK) and of its downstream target, p90(RSK).
      Moreover, FGF-2 also stimulated the transient degradation of IkappaBalpha and
      IkappaBbeta. PD098059, a specific inhibitor of p42/44(MAPK) phosphorylation,
      inhibited FGF-2-stimulated DNA synthesis, phosphorylation of p42/44(MAPK) and
      p90(RSK), and degradation of IkappaBbeta. In contrast, in chlorate-treated and
      hence sulfated glycosaminoglycan-deficient cells, FGF-2 was unable to stimulate
      DNA synthesis. However, FGF-2 was able to trigger a transient phosphorylation of
      both p42/44(MAPK) and p90(RSK), which peaked at 15 min and returned to control
      levels at 30 min. In these sulfated glycosaminoglycan-deficient cells, no
      degradation of IkappaBalpha and IkappaBbeta was observed after FGF-2 addition.
      However, in chlorate-treated cells, the addition of heparin or purified HSPGs
      simultaneously with FGF-2 restored DNA synthesis, the sustained phosphorylation
      of p42/44(MAPK) and p90(RSK), and the degradation of IkappaBalpha and
      IkappaBbeta. These results suggest that the HSPG receptor for FGF-2 not only
      influences the outcome of FGF-2 signaling, e.g. cell proliferation, but
      importantly regulates the immediate-early signals generated by this growth
      factor.

PMID- 10944533
TI  - Inhibition of Wnt signaling pathway by a novel axin-binding protein.
AB  - Axin forms a complex with adenomatous polyposis coli gene product, glycogen
      synthase kinase-3beta (GSK-3beta), beta-catenin, Dvl, and protein phosphatase 2A
      and functions as a scaffold protein in the Wnt signaling pathway. In the Axin
      complex, GSK-3beta efficiently phosphorylates beta-catenin, which is then
      ubiquitinated and degraded by proteasome. We isolated a novel protein that binds
      to Axin and named it Axam (for Axin associating molecule). Axam formed a complex
      with Axin in intact cells and bound directly to Axin. Axam inhibited the complex
      formation of Dvl with Axin and the activity of Dvl to suppress GSK-3beta
      dependent phosphorylation of Axin. Furthermore, Axam induced the degradation of
      beta-catenin in SW480 cells and inhibited Wnt-dependent axis duplication in
      Xenopus embryos. These results suggest that Axam regulates the Wnt signaling
      pathway negatively by inhibiting the binding of Dvl to Axin.

PMID- 10944534
TI  - Expression of a catalytically inactive sphingosine kinase mutant blocks agonist
      induced sphingosine kinase activation. A dominant-negative sphingosine kinase.
AB  - Sphingosine kinase (SK) catalyzes the formation of sphingosine 1-phosphate (S1P),
      a lipid messenger that plays an important role in a variety of mammalian cell
      processes, including inhibition of apoptosis and stimulation of cell
      proliferation. Basal levels of S1P in cells are generally low but can increase
      rapidly when cells are exposed to various agonists through rapid and transient
      activation of SK activity. To date, elucidation of the exact signaling pathways
      affected by these elevated S1P levels has relied on the use of SK inhibitors that
      are known to have direct effects on other enzymes in the cell. Furthermore, these
      inhibitors block basal SK activity, which is thought to have a housekeeping
      function in the cell. To produce a specific inhibitor of SK activation we sought
      to generate a catalytically inactive, dominant-negative SK. This was accomplished
      by site-directed mutagenesis of Gly(82) to Asp of the human SK, a residue
      identified through sequence similarity to the putative catalytic domain of
      diacylglycerol kinase. This mutant had no detectable SK activity when expressed
      at high levels in HEK293T cells. Activation of endogenous SK activity by tumor
      necrosis factor-alpha (TNFalpha), interleukin-1beta, and phorbol esters in
      HEK293T cells was blocked by expression of this inactive sphingosine kinase
      (hSK(G82D)). Basal SK activity was unaffected by expression of hSK(G82D).
      Expression of hSK(G82D) had no effect on TNFalpha-induced activation of protein
      kinase C and sphingomyelinase activities. Thus, hSK(G82D) acts as a specific
      dominant-negative SK to block SK activation. This discovery provides a powerful
      tool for the elucidation of the exact signaling pathways affected by elevated S1P
      levels following SK activation. To this end we have employed the dominant
      negative SK to demonstrate that TNFalpha activation of extracellular signal
      regulated kinases 1 and 2 (ERK1,2) is dependent on SK activation.

PMID- 10944535
TI  - Copper activation of superoxide dismutase 1 (SOD1) in vivo. Role for protein
      protein interactions with the copper chaperone for SOD1.
AB  - Insertion of copper into superoxide dismutase 1 (SOD1) in vivo requires the
      copper chaperone for SOD1 (CCS). CCS encompasses three protein domains: copper
      binding Domains I and III at the amino and carboxyl termini, and a central Domain
      II homologous to SOD1. Using a yeast interaction mating system, yeast CCS was
      seen to physically interact with SOD1, and this interaction required sequences at
      the predicted dimer interface of CCS Domain II. Interactions with SOD1 also
      required sequences of Domain III, but not Domain I. Mutations were introduced at
      the dimer interface of yeast SOD1, and the corresponding mutant failed to
      interact with CCS. When loaded with copper independent of CCS, this mutant SOD1
      exhibited superoxide scavenging activity, but was normally inactive in vivo
      because CCS failed to recognize the enzyme. Activation of SOD1 by CCS was also
      examined using an in vivo assay for copper incorporation into SOD1. Yeast CCS was
      observed to insert copper into a pre-existing pool of apoSOD1 without the need
      for new SOD1 synthesis or for protein unfolding by the major SSA cytosolic heat
      shock proteins. Our data are consistent with a model in which prefolded dimers of
      apoSOD1 serve as substrate for the CCS copper chaperone.

PMID- 10944536
TI  - Phg1p is a nine-transmembrane protein superfamily member involved in
      dictyostelium adhesion and phagocytosis.
AB  - To identify the molecular mechanisms involved in phagocytosis, we generated
      random insertion mutants of Dictyostelium discoideum and selected two mutants
      defective for phagocytosis. Both represented insertions in the same gene, named
      PHG1. This gene encodes a polytopic membrane protein with an N-terminal lumenal
      domain and nine potential transmembrane segments. Homologous genes can be
      identified in many species; however, their function is yet to be elucidated.
      Disruption of PHG1 caused a selective defect in phagocytosis of latex beads and
      Escherichia coli, but not Klebsiella aerogenes bacteria. This defect in
      phagocytosis was caused by a decrease in the adhesion of mutant cells to
      phagocytosed particles. These results indicate that the Phg1 protein is involved
      in the adhesion of Dictyostelium to various substrates, a crucial event of
      phagocytosis and demonstrate the usefulness of a genetic approach to dissect the
      molecular events involved in the phagocytic process.

PMID- 10944537
TI  - HIV-1 TAR RNA enhances the interaction between Tat and cyclin T1.
AB  - Human immunodeficiency virus, type 1 (HIV-1), Tat activates elongation of RNA
      polymerase II transcription at the HIV-1 promoter through interaction with the
      cyclin T1 (CycT1) subunit of the positive transcription elongation factor
      complex, P-TEFb. Binding of Tat to CycT1 induces cooperative binding of the P
      TEFb complex onto nascent HIV-1 TAR RNA. Here the specific interaction between
      Tat protein, human cyclin T1, and HIV-1 TAR RNA was analyzed by fluorescence
      resonance energy transfer, using fluorescein-labeled TAR RNA and a rhodamine
      labeled Tat protein synthesized through solid-phase chemistry. We find that CycT1
      remodels the structure of Tat to enhance its affinity for TAR RNA and that TAR
      RNA further enhances the interaction between Tat and CycT1. We conclude that TAR
      RNA nucleates the formation of the Tat.P-TEFb complex through an induced fit
      mechanism.

PMID- 10944538
TI  - Macrophages deficient in CTP:Phosphocholine cytidylyltransferase-alpha are viable
      under normal culture conditions but are highly susceptible to free cholesterol
      induced death. Molecular genetic evidence that the induction of
      phosphatidylcholine biosynthesis in free cholesterol-loaded macrophages is an
      adaptive response.
AB  - Macrophages in atherosclerotic lesions accumulate excess free cholesterol (FC)
      and phospholipid. Because excess FC is toxic to macrophages, these observations
      may have relevance to macrophage death and necrosis in atheromata. Previous work
      by us showed that at early stages of FC loading, when macrophages are still
      healthy, there is activation of the phosphatidylcholine (PC) biosynthetic enzyme,
      CTP:phosphocholine cytidylyltransferase (CT), and accumulation of PC mass. We
      hypothesized that this is an adaptive response, albeit transient, that prevents
      the FC:PC ratio from reaching a toxic level. To test this hypothesis directly, we
      created mice with macrophage-targeted disruption of the major CT gene, CTalpha,
      using the Cre-lox system. Surprisingly, the number of peritoneal macrophages
      harvested from CTalpha-deficient mice and their overall health under normal
      culture conditions appeared normal. Moreover, CT activity and PC biosynthesis and
      in vitro CT activity were decreased by 70-90% but were not absent. As a likely
      explanation of this residual activity, we showed that CTbeta2, a form of CT that
      arises from another gene, is induced in CTalpha-deficient macrophages. To test
      our hypothesis that increased PC biosynthesis is an adaptive response to FC
      loading, the viability of wild-type versus CTalpha-deficient macrophages under
      control and FC-loading conditions was compared. After 5 h of FC loading, death
      increased from 0.7% to only 2.0% in wild-type macrophages but from 0. 9% to 29.5%
      in CTalpha-deficient macrophages. These data offer the first molecular genetic
      evidence that activation of CTalpha and induction of PC biosynthesis in FC-loaded
      macrophages is an adaptive response. Furthermore, the data reveal that CTbeta2 in
      macrophages is induced in the absence of CTalpha and that a low level of residual
      CT activity, presumably due to CTbeta2, is enough to keep the cells viable in the
      peritoneum in vivo and under normal culture conditions.

PMID- 10944540
TI  - Cyclin D1 and esophageal adenocarcinoma risk: how good does a marker have to be?

PMID- 10944539
TI  - Overdiagnosis: An underrecognized cause of confusion and harm in cancer
      screening.

PMID- 10944542
TI  - Leading centers for low-dose bone marrow transplants

PMID- 10944541
TI  - How low can the doses go? Transplanters look to less toxic future.

PMID- 10944543
TI  - The next transplant frontier: treating solid tumors.

PMID- 10944544
TI  - Reports bring several changes to IRBs.

PMID- 10944546
TI  - Links to recently released reports on IRBs

PMID- 10944545
TI  - Stat bite: Highest mortality from melanoma by U.S. state, 1970-1994.

PMID- 10944547
TI  - Britain struggles to correct spending imbalances.

PMID- 10944548
TI  - Lung project update raises issue of overdiagnosing patients.

PMID- 10944549
TI  - Journal's impact factor increases

PMID- 10944550
TI  - A family of drug transporters: the multidrug resistance-associated proteins.
AB  - The human multidrug resistance-associated protein (MRP) family currently has
      seven members. The ability of several of these membrane proteins to transport a
      wide range of anticancer drugs out of cells and their presence in many tumors
      make them prime suspects in unexplained cases of drug resistance, although proof
      that they contribute to clinical drug resistance is still lacking. Recent studies
      have begun to clarify the function of the MRP family members. MRPs are organic
      anion transporters; i.e., they transport anionic drugs, exemplified by
      methotrexate, and neutral drugs conjugated to acidic ligands, such as glutathione
      (GSH), glucuronate, or sulfate. However, MRP1, MRP2, and MRP3 can also cause
      resistance to neutral organic drugs that are not known to be conjugated to acidic
      ligands by transporting these drugs together with free GSH. MRP1 can even confer
      resistance to arsenite and MRP2 to cisplatin, again probably by transporting
      these compounds in complexes with GSH. MRP4 overexpression is associated with
      high-level resistance to the nucleoside analogues 9-(2-phosphonylmethoxyethyl)
      adenine and azidothymidine, both of which are used as anti-human immunodeficiency
      virus drugs. MRPs may, therefore, also have a role in resistance against
      nucleoside analogues used in cancer chemotherapy. Mice without Mrp1, a high
      affinity leukotriene C(4) transporter, have an altered response to inflammatory
      stimuli but are otherwise healthy and fertile. MRP2 is the major transporter
      responsible for the secretion of bilirubin glucuronides into bile, and humans
      without MRP2 develop a mild liver disease known as the Dubin-Johnson syndrome.
      The physiologic functions of the other MRPs are not known. Whether long-term
      inhibition of MRPs in humans can be tolerated (assuming that suitable inhibitors
      will be found) remains to be determined.

PMID- 10944551
TI  - Promoter methylation and silencing of the retinoic acid receptor-beta gene in
      lung carcinomas.
AB  - BACKGROUND: Retinoic acid plays an important role in lung development and
      differentiation, acting primarily via nuclear receptors encoded by the retinoic
      acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and
      RARbeta4 are repressed in human lung cancers, we investigated whether methylation
      of their promoter, P2, might lead to silencing of the RARbeta gene in human lung
      tumors and cell lines. METHODS: Methylation of the P2 promoter from small-cell
      lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor
      samples was analyzed by the methylation-specific polymerase chain reaction (PCR).
      Expression of RARbeta2 and RARbeta4 was analyzed by reverse transcription-PCR.
      Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by
      electrophoretic separation of PCR products. Statistical differences were analyzed
      by Fisher's exact test with continuity correction. RESULTS: The P2 promoter was
      methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and
      cell lines, and the difference was statistically significant (two-sided P:<.001).
      By contrast, in 57 of 58 control samples, we observed only the unmethylated form
      of the gene. Four tumor cell lines with unmethylated promoter regions expressed
      both RARbeta2 and RARbeta4. Four tumor lines with methylated promoter regions
      lacked expression of these isoforms, but demethylation by exposure to 5-aza-2'
      deoxycytidine restored their expression. LOH at chromosome 3p24 was observed in
      100% (13 of 13) of SCLC lines and 67% (12 of 18) of NSCLC cell lines, and the
      difference was statistically significant (two-sided P: =.028). CONCLUSIONS:
      Methylation of the RARbeta P2 promoter is one mechanism that silences RARbeta2
      and RARbeta4 expression in many lung cancers, particularly SCLC. Chemical
      demethylation is a potential approach to lung cancer therapy.

PMID- 10944552
TI  - Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up.
AB  - BACKGROUND: The Mayo Lung Project (MLP) was a randomized, controlled clinical
      trial of lung cancer screening that was conducted in 9211 male smokers between
      1971 and 1983. The intervention arm was offered chest x-ray and sputum cytology
      every 4 months for 6 years; the usual-care arm was advised at trial entry to
      receive the same tests annually. No lung cancer mortality benefit was evident at
      the end of the study. We have extended follow-up through 1996. METHODS: A
      National Death Index-PLUS search was used to assign vital status and date and
      cause of death for 6523 participants with unknown information. The median
      survival for lung cancer patients diagnosed before July 1, 1983, was calculated
      by use of Kaplan-Meier estimates. Survival curves were compared with the log-rank
      test. RESULTS: The median follow-up time was 20.5 years. Lung cancer mortality
      was 4.4 (95% confidence interval [CI] = 3.9-4.9) deaths per 1000 person-years in
      the intervention arm and 3.9 (95% CI = 3.5-4.4) in the usual-care arm (two-sided
      P: for difference =.09). For participants diagnosed with lung cancer before July
      1, 1983, survival was better in the intervention arm (two-sided P: =.0039). The
      median survival for patients with resected early-stage disease was 16.0 years in
      the intervention arm versus 5.0 years in the usual-care arm. CONCLUSIONS:
      Extended follow-up of MLP participants did not reveal a lung cancer mortality
      reduction for the intervention arm. Similar mortality but better survival for
      individuals in the intervention arm indicates that some lesions with limited
      clinical relevance may have been identified in the intervention arm.

PMID- 10944553
TI  - Prospective study of cyclin D1 overexpression in Barrett's esophagus: association
      with increased risk of adenocarcinoma.
AB  - BACKGROUND: Esophageal adenocarcinoma commonly arises from a precancerous
      condition, Barrett's esophagus, in which the normal squamous epithelium is
      replaced by a columnar cell-lined epithelium. Genetic alterations occurring in
      this process could serve as biomarkers for the risk of malignant progression,
      improve surveillance, and contribute to early diagnosis. We examined two
      potential biomarkers, cyclin D1 and p53, in a prospective cohort of Barrett's
      esophagus patients. METHODS: A total of 307 patients were enrolled in an
      endoscopic surveillance cohort, and esophageal biopsy specimens were collected at
      each endoscopy. Incident cases of adenocarcinoma were matched to control patients
      within the cohort by duration of follow-up, age, sex, and length of columnar cell
      lined epithelium at recruitment. Biopsy specimens were analyzed for cyclin D1 and
      p53 protein levels by immunohistochemistry. Statistical tests were two-sided.
      RESULTS: A total of 12 cases of adenocarcinoma occurred within the follow-up
      period, and tumor biopsy specimens from 11 cases stained positive for cyclin D1.
      Biopsy specimens from eight of these patients taken at recruitment also stained
      positive for cyclin D1. A case-control analysis of biopsy specimens obtained at
      recruitment revealed a statistically significantly increased risk of progression
      to adenocarcinoma in Barrett's esophagus patients whose biopsy specimens were
      cyclin D1 positive (odds ratio [OR] = 6. 85; 95% confidence interval [CI] = 1.57
      29.91; P =.0106) but not in patients whose biopsy specimens were p53 positive (OR
      = 2.99; 95% CI = 0.57-15.76; P =.197). CONCLUSIONS: Cyclin D1-positive staining
      could be a useful biomarker in identifying Barrett's esophagus patients at high
      risk of esophageal adenocarcinoma. Given the complexity of genetic alterations in
      the natural history of this cancer, additional biomarkers will be required to
      increase the sensitivity and specificity of molecular diagnosis.

PMID- 10944554
TI  - Decision framework for chemotherapeutic interventions for metastatic non-small
      cell lung cancer.
AB  - BACKGROUND: Best supportive care has long been considered to be the standard
      therapy for metastatic non-small-cell lung cancer (NSCLC). There is now evidence
      from randomized trials that a number of chemotherapy regimens can palliate cancer
      related symptoms and modestly improve survival. We show how cost-effectiveness
      analyses can be used to make choices between different (ambulatory) chemotherapy
      regimens. METHODS: Clinical algorithms describing the diagnosis, staging, and
      treatment of metastatic NSCLC were incorporated into Statistics Canada's
      Population Health Model. Using consistent methodology, we assessed the cost
      effectiveness of several chemotherapeutic interventions: a combination of
      vindesine (VDS) plus cisplatin, etoposide (VP-16) plus cisplatin, vinblastine
      (VLB) plus cisplatin, vinorelbine (Navelbine; NVB) plus cisplatin, paclitaxel
      (Taxol) plus cisplatin, and gemcitabine (GEM) and NVB alone. We calculated the
      total chemotherapy costs in 1995 Canadian dollars, the cost per case, the average
      life-years saved, and the cost per life-year saved. Using the Population Health
      Model, we then constructed an advanced decision framework that rank-ordered the
      various treatment regimens so as to optimize benefit below various cost
      effectiveness thresholds. RESULTS: One regimen (VLB plus cisplatin) appears to
      result in better survival and lower health care expenditures than best supportive
      care. By use of cost-effectiveness thresholds of $25,000 and $50,000 per life
      year gained, NVB plus cisplatin is the preferred regimen. When quality of life is
      considered, however, GEM is preferred to NVB plus cisplatin at a threshold value
      of $50,000. At thresholds of $75 000 and $100,000, paclitaxel plus cisplatin at a
      dose of 135 mg/m(2) is the preferred regimen. At thresholds of $50,000 and above,
      best supportive care is the least preferred regimen. CONCLUSIONS: This decision
      framework allows the comparison of different treatment regimens based on various
      cost-effectiveness thresholds. Our analysis also supports the use of chemotherapy
      regimens and the abandonment of best supportive care as the standard of care for
      patients with advanced NSCLC. [J Natl Cancer Inst 2000;92:1321-9].

PMID- 10944555
TI  - Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of
      angiogenesis.
AB  - BACKGROUND: Angiogenesis, the development of new blood vessels from pre-existing
      vasculature, is a prerequisite for tumor growth and metastasis. Surrogate markers
      for angiogenesis would be useful for studying the effectiveness of
      antiangiogenesis drugs. We examined the potential of three serum glycoproteins
      vascular cell adhesion molecule-1 (VCAM-1), endothelial selectin (E-selectin),
      and von Willebrand factor (VWF)-to serve as markers for angiogenesis. METHODS:
      Preoperative serum levels of VCAM-1, E-selectin, and VWF were measured by enzyme
      linked immunosorbent assay in 93 women with early breast cancer and were compared
      with microvessel density in each tumor, histologic features, and recurrence after
      surgery. Serum samples were taken from 55 women with advanced breast cancer who
      were commencing hormonal therapy, both immediately before therapy and 3 months
      later. Changes in serum levels of VCAM-1, E-selectin, and VWF were compared with
      the response of the disease to hormonal therapy assessed 6 months after the start
      of hormone therapy or at disease progression. All P: values are two-sided.
      RESULTS: In women with early breast cancer, serum levels of VCAM-1 (but not of E
      selectin or VWF) correlated closely with microvessel density in tumors (r =.65;
      P:<.001), and women who developed early recurrence had higher preoperative levels
      of serum VCAM-1 than those who remained disease free (P: =.01). Serum VCAM-1
      levels rose in women with advanced breast cancer whose disease progressed
      (P:<.001) but remained unchanged or fell in women with advanced breast cancer
      whose disease remained stable or showed a partial response to hormonal therapy.
      CONCLUSION: Serum VCAM-1 appears to be a surrogate marker of angiogenesis in
      breast cancer. Its measurement may, therefore, help in the assessment of
      antiangiogenesis drugs currently in phase II trials.

PMID- 10944556
TI  - Real-time quantitative polymerase chain reaction assessment of immune reactivity
      in melanoma patients after tumor peptide vaccination.
AB  - BACKGROUND: Monitoring the immune response to epitope-specific vaccination in
      cancer patients is important for vaccine development. The traditional method, in
      which the in vitro sensitization of peripheral blood mononuclear cells (PBMCs)
      with epitope is compared before and after vaccination, is time-consuming and
      allows only a qualitative assessment of the response. We used a rapid,
      quantitative, real-time polymerase chain reaction (PCR) assay to directly measure
      the immune reactivity of patients' PBMCs to the vaccine epitope. METHODS: PBMCs
      were obtained from melanoma patients before and after two rounds of vaccination
      with either g209-2M, a peptide derived from melanoma protein gp100 (n = 24), or
      ESg209-2M, a modified version of this peptide (n = 20). PBMCs were tested for
      immune reactivity by assaying interferon gamma (IFN gamma) protein release after
      in vitro sensitization with the epitope or for IFN gamma messenger RNA expression
      by real-time PCR. A twofold or more increase in IFN gamma protein release or a
      1.5-fold or more increase in IFN gamma transcript accumulation in PBMCs after
      vaccination was considered to be evidence of a specific response. Correlation
      between the two methods was tested by use of the Spearman correlation coefficient
      after the results were ranked as positive or negative. All statistical tests were
      two-sided. RESULTS: The results obtained with the two methods were strongly
      correlated (Spearman's rho = 0.72; P =.0006). The g209-2M and Esg209-2M peptides
      resulted in similar percentages of vaccine-specific reactivity in PBMCs after in
      vitro sensitization (63% and 65% of patients, respectively; Fisher's exact test P
      =.6 for comparison of the two groups). The PCR method could detect vaccine
      specific reactivity in a subset of patients (38% and 35% of patients,
      respectively; Fisher's exact test P =.7 for comparison of the two groups).
      CONCLUSION: Vaccination induces circulating antitumor lymphocytes, albeit in low
      frequencies, capable of directly reacting with tumor antigen. PBMCs of vaccinated
      individuals can respond to a vaccine-specific stimulus in a direct assay that
      does not require prolonged in vitro manipulations.

PMID- 10944557
TI  - Randomized trial of a specialist genetic assessment service for familial breast
      cancer.
AB  - BACKGROUND: Because of the growing demand for genetic assessment, there is an
      urgent need for information about what services are appropriate for women with a
      family history of breast cancer. Our purpose was to compare the psychologic
      impact and costs of a multidisciplinary genetic and surgical assessment service
      with those of current service provisions. METHODS: We carried out a prospective
      randomized trial of surgical consultation with (the trial group) and without (the
      control group) genetic assessment in 1000 women with a family history of breast
      cancer. All P: values are from two-sided tests. RESULTS: Although statistically
      significantly greater improvement in knowledge about breast cancer was found in
      the trial group (P: =.05), differences between groups in other psychologic
      outcomes were not statistically significant. Women in both groups experienced
      statistically significant reductions in anxiety and found attending the clinics
      to be highly satisfying. An initial specialist genetic assessment cost pound
      14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling
      and genetic testing of affected relatives, plus subsequent testing of family
      members of affected relatives identified as mutation carriers, raised the total
      extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S.
      $96.35) over costs for the control subjects. CONCLUSIONS: There may be little
      benefit in providing specialist genetics services to all women with a family
      history of breast cancer. Further investigation of factors that may mediate the
      impact of genetic assessment is in progress and may reveal subgroups of women who
      would benefit from specialist genetics services.

PMID- 10944558
TI  - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a carcinogen in high-temperature
      cooked meat, and breast cancer risk.

PMID- 10944560
TI  - Current controversies in bone marrow transplantation

PMID- 10944559
TI  - Chromosome 19 translocation, overexpression of Notch3, and human lung cancer.

PMID- 10944561
TI  - Race, grade level, and cigarette smoking: the 1999 National Youth Tobacco Survey.

PMID- 10944562
TI  - Patterns of brain activation in people at risk for Alzheimer's disease.
AB  - BACKGROUND: The epsilon4 allele of the apolipoprotein E gene (APOE) is the chief
      known genetic risk factor for Alzheimer's disease, the most common cause of
      dementia late in life. To determine the relation between brain responses to tasks
      requiring memory and the genetic risk of Alzheimer's disease, we performed APOE
      genotyping and functional magnetic resonance imaging (MRI) of the brain in older
      persons with intact cognition. METHODS: We studied 30 subjects (age, 47 to 82
      years) who were neurologically normal, of whom 16 were carriers of the APOE
      epsilon4 allele and 14 were homozygous for the APOE epsilon3 allele. The mean age
      and level of education were similar in the two groups. Patterns of brain
      activation during functional MRI scanning were determined while subjects
      memorized and recalled unrelated pairs of words and while subjects rested between
      such periods. Memory was reassessed in 14 subjects two years later. RESULTS: Both
      the magnitude and the extent of brain activation during memory-activation tasks
      in regions affected by Alzheimer's disease, including the left hippocampal,
      parietal, and prefrontal regions, were greater among the carriers of the APOE
      epsilon4 allele than among the carriers of the APOE epsilon3 allele. During
      periods of recall, the carriers of the APOE epsilon4 allele had a greater average
      increase in signal intensity in the hippocampal region (1.03 percent vs. 0.62
      percent, P<0.001) and a greater mean (+/-SD) number of activated regions
      throughout the brain (15.9+/-6.2 vs. 9.4+/-5.5, P=0.005) than did carriers of the
      APOE epsilon3 allele. Longitudinal assessment after two years indicated that the
      degree of base-line brain activation correlated with degree of decline in memory.
      CONCLUSIONS: Patterns of brain activation during tasks requiring memory differ
      depending on the genetic risk of Alzheimer's disease and may predict a subsequent
      decline in memory.

PMID- 10944563
TI  - Racecadotril in the treatment of acute watery diarrhea in children.
AB  - BACKGROUND: Racecadotril (acetorphan), an enkephalinase inhibitor with
      antisecretory and antidiarrheal actions, is an effective and safe treatment for
      acute diarrhea in adults and children. Whether treatment with racecadotril and
      oral rehydration therapy is more effective than treatment with oral rehydration
      alone in hospitalized children with acute watery diarrhea is not known. METHODS:
      We treated 135 boys 3 to 35 months of age who had watery diarrhea of five days'
      duration or less with racecadotril (1.5 mg per kilogram of body weight orally
      every eight hours) or placebo, in addition to oral rehydration solution. The
      primary end point was the 48-hour stool output (measured in grams); the total
      stool output, duration of diarrhea, and total intake of oral rehydration solution
      were also measured. RESULTS: The mean (+/-SE) 48-hour stool output was 92+/-12 g
      per kilogram in the racecadotril group and 170+/-15 g per kilogram in the placebo
      group (P<0.001), a 46 percent reduction with racecadotril. The results were
      similar among the 73 boys with rotavirus infections. The total stool output was
      157+/-27 g per kilogram in the racecadotril group and 331+/-39 g per kilogram in
      the placebo group (P<0.001). The median duration of diarrhea was significantly
      less (P<0.001) in the racecadotril group (28 hours regardless of rotavirus
      status) than in the placebo group (72 and 52 hours, respectively, for rotavirus
      positive and rotavirus-negative patients). The intake of oral rehydration
      solution was significantly lower in the racecadotril group than in the placebo
      group (P<0.001). Racecadotril was well tolerated; only seven patients taking
      racecadotril had adverse effects, which were all mild and transient. CONCLUSIONS:
      In young boys with acute watery diarrhea, racecadotril is an effective and safe
      treatment.

PMID- 10944564
TI  - Images in clinical medicine. Spontaneous duodenal hematoma during oral
      anticoagulation.

PMID- 10944565
TI  - Enrollment of women in cardiovascular clinical trials funded by the National
      Heart, Lung, and Blood Institute.
AB  - BACKGROUND: With the recognition that certain aspects of cardiovascular disease
      are specific to sex, the government has sought to ensure that federally funded
      clinical research yields adequate high-quality information about heart disease in
      women. METHODS: We tabulated the numbers of men and women in cardiovascular
      clinical trials funded by the National Heart, Lung, and Blood Institute (NHLBI)
      between 1965 and 1998, recording both total numbers and the numbers for each type
      of cardiovascular disease. We analyzed the data according to the sex-specific
      prevalence of disease and assessed changes in enrollment over time. We performed
      a similar analysis after excluding all single-sex trials. RESULTS: A total of
      398,801 subjects (215,796 women and 183,005 men) were enrolled in NHLBI-funded
      studies of cardiovascular disease. The overall enrollment rate for women (54
      percent) exceeded the prevalence of cardiovascular disease in women in the
      general population (49 percent) and increased over time (P=0.002). With single
      sex trials excluded, the enrollment rate for women was 38 percent, which did not
      change significantly over time. In studies of coronary artery disease and
      hypertension the rates of enrollment of women were similar to or exceeded the
      prevalence of these disorders in women. The enrollment rate increased
      significantly over time in studies of coronary artery disease (P<0.001) but not
      in studies of hypertension or arrhythmia. Women were under-enrolled in studies of
      heart failure, and the rate of enrollment did not change significantly over time.
      When single-sex trials were excluded from the analysis of enrollment rates
      according to the prevalence of disease, the results were similar. There was no
      change in enrollment rates overtime for any category of disease. CONCLUSIONS:
      Federal efforts to increase the representation of women in clinical trials have
      been moderately successful primarily because of the institution of a small number
      of large, single-sex trials involving coronary artery disease. There has been no
      change in the sex composition of cohorts in the majority of studies of
      cardiovascular disease.

PMID- 10944566
TI  - Epstein-Barr virus infection.

PMID- 10944567
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 25-2000. A 69-year-old woman with pleuritic pain and a pulmonary
      arterial obstruction.

PMID- 10944568
TI  - Detection of preclinical Alzheimer's disease.

PMID- 10944569
TI  - Composite-tissue transplantation--a new frontier.

PMID- 10944571
TI  - Correction: Collective Bargaining for House Staff.

PMID- 10944570
TI  - Women in clinical trials--a portfolio for success.

PMID- 10944572
TI  - Correction: The Acute Respiratory Distress Syndrome.

PMID- 10944573
TI  - Lawrence E. Scheving, Ph.D.: chronobiology pioneer, "Full Bird" Colonel, and
      native son.

PMID- 10944574
TI  - Neurogenesis and stem cells in adult mammalian dorsal root ganglia.

PMID- 10944575
TI  - Biological time and in vivo research: a field guide to pitfalls.
AB  - Biological rhythmicity is a fundamental characteristic of all life forms, from
      primitive bacteria to man. The molecular biology, genetics, and the neurobiology
      of the biological clock(s) are being elucidated. Daily (circadian) statistically
      significant fluctuations occur in all of the normal biological variables studied
      in the experimental animal and the human. Many researchers, however, are not
      aware of the negative impact biological rhythmicity can have on experimental
      design and/or data interpretation. This article serves not as a review, but as a
      "field guide" to the pitfalls that can occur when research is performed in the
      absence of an understanding of biological rhythmicity. The major topics discussed
      are: 1) data transfer from the diurnally in-active/resting/sleeping lab animal to
      the diurnally active human, 2) frequency of sampling, 3) free-running vs.
      synchronization, 4) alternating periods of resistance and susceptibility, 5)
      phase shifting of a rhythm, 6) the assumption that one mean +/- S.E. from control
      animals can be "stretched" across an experimental time span, and 7) plotting data
      on an "hours after treatment" format vs. a "time of day" format. The hope is that
      by avoiding the pitfalls, biological time will become an ally in the endeavor to
      understand human biology.

PMID- 10944577
TI  - Forthcoming topics

PMID- 10944576
TI  - New ideas about binocular coordination of eye movements: is there a chameleon in
      the primate family tree?
AB  - Many animals with laterally placed eyes, such as chameleons, move their eyes
      independently of one another. In contrast, primates with frontally placed eyes
      and binocular vision must move them together so that both eyes are aimed at the
      same point in visual space. Is binocular coordination an innate feature of how
      our brains are wired, or have we simply learned to move our eyes together? This
      question sparked a controversy in the 19(th) century between two eminent German
      scientists, Ewald Hering and Hermann von Helmholtz. Hering took the position that
      binocular coordination was innate and vigorously challenged von Helmholtz's view
      that it was learned. Hering won the argument and his hypothesis, known as
      Hering's Law of Equal Innervation, became generally accepted. New evidence
      suggests, however, that similar to chameleons, primates may program movements of
      each eye independently. Binocular coordination is achieved by a neural network at
      the motor periphery comprised of motoneurons and specialized interneurons located
      near or in the cranial nerve nuclei that innervate the extraocular muscles. It is
      assumed that this network must be trained and calibrated during infancy and
      probably throughout life in order to maintain the precise binocular coordination
      characteristic of primate eye movements despite growth, aging effects, and
      injuries to the eye movement neuromuscular system. Malfunction of this network or
      its ability to adaptively learn may be a contributing cause of strabismus.

PMID- 10944578
TI  - Intercalation of cell fates during tarsal development in Drosophila.
AB  - The process of proximal-distal (PD) patterning in animal appendages requires the
      generation of positional values as they grow away from the main body axes. In the
      Drosophila leg some PD fates are intercalated between previously existing ones.
      In a recent study, Kojima et al. describe a role for the homeobox gene Bar in
      patterning of the distal region of the leg. Their work highlights fundamental
      aspects of PD development, such as the fashion in which new PD values appear, the
      importance of regulatory relationships between PD genes, and correlation of their
      patterns of expression with morphogenesis and differentiation.

PMID- 10944579
TI  - Homologous tails? Or tales of homology?
AB  - Classical mutations at the mouse Brachyury (T) locus were discovered because they
      lead to shortened tails in heterozygous newborns. no tail (ntl) mutants in the
      zebrafish, as their name suggests, show a similar phenotype. In Drosophila,
      mutants in the brachyenteron (byn) gene disrupt hindgut formation. These genes
      all encode T-box proteins, a class of sequence-specific DNA binding proteins and
      transcription factors. Mutations in the C. elegans mab-9 gene cause massive
      defects in the male tail because of failed fate decisions in two tail progenitor
      cells. In a recent paper, Woollard and Hodgkin have cloned the mab-9 gene and
      found that it too encodes a T-box protein, similar to Brachyury in vertebrates
      and brachyenteron in Drosophila. The authors suggest that their results support
      models for an evolutionarily ancient role for these genes in hindgut formation.
      We will discuss this proposal and try to decide whether the gene sequences, gene
      interactions and gene expression patterns allow any conclusions to be made about
      the rear end of the ancestral metazoan.

PMID- 10944580
TI  - Transcriptional regulation: a new dominion for inositol phosphate signaling?
AB  - The diverse phosphorylation patterns of the six-carbon inositol ring generates a
      mesmerizing wealth of inositol phosphates but we have little insight into the
      precise cellular roles of most members of this family. Therefore, new information
      on these roles is very welcome. The discovery by two independent groups(1, 2)
      that the Arg82 transcriptional regulator from Saccharomyces cerevisiae has
      inositol phosphate kinase activity is intriguing in this respect. One group
      proposes that these events directly affect the function of a specific, multimeric
      transcriptional complex.(2) It will be argued here, however, that available data
      do not entirely support such a direct role for Arg82 in transcription. The
      potential relevance of these findings to higher organisms will also be discussed.

PMID- 10944581
TI  - Changing genetic information through RNA editing.
AB  - RNA editing, the post-transcriptional alteration of a gene-encoded sequence, is a
      widespread phenomenon in eukaryotes. As a consequence of RNA editing,
      functionally distinct proteins can be produced from a single gene. The molecular
      mechanisms involved include single or multiple base insertions or deletions as
      well as base substitutions. In mammals, one type of substitutional RNA editing,
      characterized by site-specific base-modification, was shown to modulate important
      physiological processes. The underlying reaction mechanism of substitutional RNA
      editing involves hydrolytic deamination of cytosine or adenosine bases to uracil
      or inosine, respectively. Protein factors have been characterized that are able
      to induce RNA editing in vitro. A supergene family of RNA-dependent deaminases
      has emerged with the recent addition of adenosine deaminases specific for tRNA.
      Here we review the developments that have substantially increased our
      understanding of base-modification RNA editing over the past few years, with an
      emphasis on mechanistic differences, evolutionary aspects and the first insights
      into the regulation of editing activity.

PMID- 10944582
TI  - Evolution of odorant receptors.
AB  - Odorant receptors (ORs) located in the nasal epithelium, at the ciliated surface
      of olfactory sensory neurons, represent the initial step of a transduction
      cascade that leads to odor detection. ORs form the largest and most diverse
      family of G-protein-coupled receptors (GPCRs). They are encoded by a multigene
      family that has been partially characterized in cyclostomes, teleosts, amphibia,
      birds and mammals, as well as in Drosophila melanogaster and the nematode
      Caenorhabditis elegans. As new sequence data emerge, it is increasingly clear
      that OR primary structure can vary dramatically across phyla. Some chemoreceptors
      are encoded by genes with little sequence similarity to the prototypical ORs
      originally isolated in mammals. A large number of sequences are now available
      allowing a detailed study of the evolutionary implications of OR diversity across
      species. This review discusses the evolutionary implications of the divergent
      primary structures of chemoreceptors with identical functions.

PMID- 10944583
TI  - Coding of neuronal differentiation by calcium transients.
AB  - Excitability has long been recognized as the basis for rapid signaling in the
      mature nervous system, but roles of channels and receptors in controlling slower
      processes of differentiation have been identified only more recently. Voltage
      dependent and transmitter-activated channels are often expressed at early stages
      of development prior to synaptogenesis, and allow influx of Ca(2+). Here we
      examine the functions of spontaneous transient elevations of intracellular Ca(2+)
      in embryonic neurons. These Ca(2+) transients abruptly raise levels of Ca(2+) as
      much as tenfold, for brief periods, repeatedly, and can be highly localized. Like
      cloudbursts on the developing landscape, Ca(2+) transients modulate growth and
      stimulate differentiation, in a frequency-dependent manner, probably by changes
      in phosphorylation or proteolysis of regulatory and structural proteins in local
      regions. We review the mechanisms by which Ca(2+) transients are generated and
      their effects in regulating motility via the cytoskeleton and differentiation via
      transcription.

PMID- 10944584
TI  - Integrating the MAP kinase signal into the G1 phase cell cycle machinery.
AB  - Growth factors and the extracellular matrix provide the environmental cues that
      control the proliferation of most cell types. The binding of growth factors and
      matrix proteins to receptor tyrosine kinases and integrins, respectively,
      regulates several cytoplasmic signal transduction cascades, among which
      activation of the mitogen-activated protein kinase cascade, ras --> Raf --> MEK -
      > ERK, is perhaps the best characterized. Curiously, ERK activation has been
      associated with both stimulation and inhibition of cell proliferation. In this
      review, we summarize recent studies that connect ERK signaling to G1 phase cell
      cycle control and suggest that the cellular response to an ERK signal depends on
      both ERK signal intensity and duration. We also discuss studies showing that
      receptor tyrosine kinases and integrins differentially regulate the ERK signal in
      G1 phase.

PMID- 10944585
TI  - The puzzling multiple lives of PML and its role in the genesis of cancer.
AB  - PML, the gene associated with acute promyelocytic leukemia (APL); PML, the target
      of numerous viral agents; PML, the growth suppressor; PML, the mediator of
      multiple apoptotic pathways; PML, the tumor suppressor; PML, the protein which
      epitomizes a novel nuclear structure, the nuclear body; PML, the transcription co
      factor. Despite the recent flurry of reports attributing multiple biological
      roles to the PML protein, PML still lacks a definitive biochemical function. This
      is probably the reason why PML is so attractive to many investigators. Here, we
      will summarize the facts and speculations on this puzzling protein.

PMID- 10944586
TI  - Histone acetylation and an epigenetic code.
AB  - The enzyme-catalyzed acetylation of the N-terminal tail domains of core histones
      provides a rich potential source of epigenetic information. This may be used both
      to mediate transient changes in transcription, through modification of promoter
      proximal nucleosomes, and for the longer-term maintenance and modulation of
      patterns of gene expression. The latter may be achieved by setting specific
      patterns of histone acetylation, perhaps involving acetylation of particular
      lysine residues, across relatively large chromatin domains. The histone
      acetylating and deacetylating enzymes (HATs and HDACs, respectively) can be
      targeted to specific regions of the genome and show varying degrees of substrate
      specificity, properties that are consistent with a role in maintaining a dynamic,
      acetylation-based epigenetic code. The code may be read (ie. exert a functional
      effect) either through non-histone proteins that bind in an acetylation-dependent
      manner, or through direct effects on chromatin structure. Recent evidence raises
      the interesting possibility that an acetylation-based code may operate through
      both mitosis and meiosis, providing a possible mechanism for germ-line
      transmission of epigenetic changes.

PMID- 10944587
TI  - Defining sameness: historical, biological, and generative homology.
AB  - Current debate concerning homology arises from three different research interests
      phylogenetics, character evolution, and generative pathways. Phylogenetic
      homology focuses on descent of the character from a common ancestor. Biological
      homology addresses character evolution and diversification. Exceptions to the
      general case complicate these two approaches: historically and biologically
      homologous characters may be produced by different generative pathways, and
      minutely similar characters produced by the same generative pathways may have a
      sporadic phylogenetic distribution. We suggest that for studies of comparative
      developmental biology, new descriptive terms are needed to distinguish similar
      structures that result from the same generative pathways from those that result
      from different generative pathways. The terms syngeny, meaning "same genesis",
      and allogeny, meaning "different genesis", allow the acknowledgement of sameness
      at the generative level and can be used in combination with the terminology of
      historical homology and biological homology to describe any given character.

PMID- 10944588
TI  - Fission yeast on the brink of meiosis.
AB  - The fission yeast Schizosaccharomyces pombe (S. pombe) is now well established as
      a versatile genetic model organism. It is widely used to analyse the basic
      eukaryotic cell cycle during vegetative growth and it is also well suited to
      studies on the elementary processes of sexual reproduction, including
      intercellular communication and signal transduction in zygote formation, as well
      as meiosis before sporulation. Systematic mutant screening has contributed much
      to our current understanding of unicellular differentiation in S. pombe, and
      structural analysis has revealed a simplified meiotic prophase with abundant
      crossing-over but no homologue synapsis. This article is a personal account of
      how this branch of fission yeast genetics has developed.

PMID- 10944589
TI  - Coilin, more than a molecular marker of the cajal (coiled) body.
AB  - The Cajal (coiled) body is a discrete nuclear organelle that was first described
      in mammalian neurons in 1903. Because the molecular composition, structure, and
      function of Cajal bodies were unknown, these enigmatic structures were largely
      ignored for most of the last century. The Cajal body has now regained the
      interest of biologists, due to the isolation of a protein marker, coilin. Despite
      current widespread use of coilin to identify Cajal bodies in various cell types,
      its structure and function are still little understood. Here, I would like to
      discuss what we have learned about coilin and suggest a possible role for coilin
      in RNA processing and cellular trafficking, especially in relation to Cajal
      bodies and nucleoli. Although coilin has been investigated primarily in somatic
      cells, I will emphasize the advantages of using the amphibian oocyte to study
      nuclear proteins and organelles.

PMID- 10944590
TI  - Historical baggage in biology: the case of 'higher' and 'lower' species.

PMID- 10944591
TI  - A systematic review of the role of human papilloma virus (HPV) testing within a
      cervical screening programme: summary and conclusions.
AB  - A systematic review of the available evidence on the role of HPV testing in
      cervical screening has been published by the Health Technology Assessment
      Committee of the UK Department of Health. The review summarized relevant data on
      testing methods, natural history, and prevalence of the virus in different
      disease groups. Cost-effectiveness modelling was undertaken. Ten major
      conclusions were reached and are reported here. The key conclusions were that HPV
      testing was more sensitive than cytology, but that there were concerns about
      specificity, especially in young women. The increased sensitivity led to a
      recommendation that HPV testing be introduced on a pilot basis for women with
      borderline and mild smears. HPV testing has great potential as a primary
      screening test, but large trials are needed to properly evaluate this application
      and to determine if its introduction can reduce invasive cancer rates. There is
      an urgent need to undertake a large trial of HPV testing in conjunction with
      other new technologies (liquid-based cytology and computer-assisted cytology
      reading) to determine the best way to integrate them into ongoing screening
      programmes. A range of issues including the age to start and stop screening, the
      appropriate screening interval, the role of self-sampling for HPV testing and the
      choice of primary test (HPV and/or cytology) require further evaluation.

PMID- 10944592
TI  - Advanced-stage cervix cancer: rapid tumour growth rather than late diagnosis.
AB  - Either diagnostic delay or tumour biology are possible factors governing the
      degree of spread at diagnosis of cervical cancer. To try to identify the most
      important parameter contributing to advanced stage, the duration of symptoms were
      recorded from patients scheduled for radiotherapy (n = 141) or radical
      hysterectomy (n = 36). In 146 cases tumour proliferation rates were evaluated
      following in vivo labelling with the DNA precursor BrdUrd. For symptomatic
      patients there was no association between duration of symptoms and stage at
      presentation. There was a significant trend for patients with increasing tumour
      stage to have more rapidly proliferating tumours with higher mean labelling index
      (LI) measurements (P = 0.001) and a shorter mean potential doubling time (Tpot)
      (P = 0.023). Socio economic deprivation may be associated with shorter Tpot
      values. The conclusion from this data is that stage at diagnosis is more
      dependent on the biological behaviour of the tumour, as expressed by
      proliferation rates, than delay in presentation.

PMID- 10944593
TI  - Lung metastases from melanoma: when is surgical treatment warranted?
AB  - Surgical treatment of lung metastases from melanoma is highly controversial as
      the expected outcome is much poorer than for other primary tumours and a reliable
      system for selecting patients is lacking. This study evaluated the long-term
      results of lung metastasectomy for melanoma, with the aim of defining a subset of
      patients with better prognosis. By reviewing the data of the International
      Registry of Lung Metastases (IRLM), we identified 328 patients who underwent lung
      metastasectomy for melanoma in the period 1945-1995. Survival was calculated by
      Kaplan-Meier estimate, using log-rank test and Cox regression model for
      statistical analysis. After complete pulmonary metastasectomy (282 patients) the
      5- and 10-year survival was 22% and 16%, respectively. In this group of patients,
      a time to pulmonary metastases (TPM) shorter than 36 months or the presence of
      multiple metastases were independent unfavourable prognostic factors. There were
      no long-term survivors after incomplete resection (46 patients, P< 0.01). Using
      the IRLM grouping system, patients without risk factors (TPM > 36 months and
      single lesion) experienced the best survival (29% at 5 years), followed by those
      with one risk factor only (20% at 5 years). On the other hand, those with two
      risk factors or incomplete resection showed a significantly poorer survival (7%
      and 0% at 5 years). Surgery plays an important role in carefully selected cases
      of pulmonary metastatic melanoma. The prognostic grouping system proposed by the
      International Registry of Lung Metastases provides a simple and effective method
      for improving the selection of surgical candidates.

PMID- 10944594
TI  - Gemcitabine plus vinorelbine in elderly or unfit patients with non-small cell
      lung cancer.
AB  - Cisplatin-based combinations are efficacious in increasing the overall survival
      of patients with non-small cell lung cancer (NSCLC), but their toxicity makes
      them unsuitable for elderly and unfit patients. The primary objective of this non
      randomized phase II study was to evaluate the feasibility and activity of the
      gemcitabine plus vinorelbine combination in previously untreated elderly and/or
      unfit patients with measurable stage III or IV NSCLC. Forty-three patients aged
      >/= 65 years or with contraindications against cisplatin treatment (36 males and
      seven females: median age 66 years; range 48-75: PS 0 = 11, PS 1 = 19, PS 2 = 13)
      received intravenous (i.v.) gemcitabine 1000 mg m(-2), followed by vinorelbine 25
      mg m(-2)i.v. on day 1 and 8 every 21 days. Fifteen patients (34.9%) achieved
      partial remission (confidence interval: 27. 6-42.2%) for a median duration of 6
      months; the median survival of these patients has not yet been reached. A further
      15 had stable disease for a median of 4 months and a median survival of 7 months.
      The 10 patients (23.2%) who experienced disease progression had a median survival
      of 4 months. Three patients are not evaluable. The 1-year actuarial survival rate
      is 31.1%. The treatment was well tolerated: only 35% of the patients had grade 3
      or 4 granulocytopenia on day 14, none experienced episodes of neutropenic fever,
      and there was no evidence of severe haematological toxicity upon recycling. Only
      9% of the patients suffered from gastrointestinal toxicity (grade 3); increased
      but reversible transaminase levels were observed in 11.6%. In conclusion, the
      results of this phase II study show that the combination of gemcitabine and
      vinorelbine is active and well tolerated in NSCLC, and thus encourage its use in
      elderly or unfit patients.

PMID- 10944595
TI  - Long-term quality of life in premenopausal women with node-negative localized
      breast cancer treated with or without adjuvant chemotherapy.
AB  - Our purpose was to evaluate the late physical and psychosocial difficulties of
      premenpausal patients treated for a localized breast cancer and to weigh the
      impact of chemotherapy on long-term quality of life. Two self-administered
      questionnaires, the EORTC core QLQ-C30 and the breast module (BR23) were mailed
      to 179 premenopausal node-negative women continuously disease-free, previously
      enrolled in a trial testing the efficacy of adjuvant CMF chemotherapy (Espie et
      al, 1997). The core questionnaire evaluates the physical, role, emotional,
      cognitive and social functioning and global health status. The breast module
      includes four functional scales: body image, sexual functioning, sexual enjoyment
      and future perspective. It also includes symptom scales such as arm or breast
      symptoms. Some specific professional and social states were added. 119 (68%)
      patients (mean age 54 years, range 30-69) participated. Mean follow-up time since
      diagnosis was 9.6 years (4-16). 68% had conservative and 32% radical surgery
      (with reconstructive surgery in 50%). CMF was given to 77 (65%) patients.
      Irradiation was administered in 75% of patients irrespective of adjuvant therapy.
      QLQ-C30 scale scores were similar in patients who had or had not received
      chemotherapy. Disturbance in body image, sex life and breast symptoms did not
      differ between patients who had or had not received adjuvant CMF. No major
      socioprofessional difficulties were reported except problems in borrowing from
      banks not related to past chemotherapy. With long follow-up, most premenopausal
      women treated for a localized breast cancer cope with the disease and its
      treatments. Adjuvant CMF chemotherapy does not appear to impair quality of life
      nor social and professional life in these patients.

PMID- 10944596
TI  - Capecitabine in the treatment of metastatic renal cell carcinoma.
AB  - To evaluate the therapeutic effects and systemic toxicities of a capecitabine
      based home therapy regimen in patients with metastatic renal cell carcinoma, 30
      patients were enrolled in a phase II clinical trial. Treatment consisted of oral
      capecitabine combined with subcutaneous recombinant human interferon-alpha 2a,
      recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two
      (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an
      overall objective response rate of 34% (95% CI 17-53%). Except one, all responses
      are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs,
      respectively. Additionally, 12 patients (40%) reached stable disease. Eight
      patients (27%) showed continued disease progression despite treatment. Therapy
      was well tolerated and was given in the outpatient setting. Capecitabine-related
      World Health Organization (WHO) grade 2 and 3 toxicities were observed in five
      and two patients respectively, and were limited to fatigue, nausea/vomiting,
      diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of
      capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result
      in a reduced therapeutic efficacy and showed significant anti-tumour activity in
      patients with advanced renal cell carcinoma.

PMID- 10944598
TI  - A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer
      patients with solid tumours.
AB  - Because tumour cell proliferation is highly dependent upon up-regulation of de
      novo polyamine synthesis, inhibition of the polyamine synthesis pathway
      represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a
      new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine
      decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC
      inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing
      confirmed promising antiproliferative activity. In this phase I study, SAM486A
      was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled
      with advanced/refractory disease not amenable to established treatments, PS </=
      2, adequate marrow, liver, renal and cardiac function. Doses were escalated in
      100% increments without toxicity in 24 pts from 3 mg m(-2)cycle(-1)up to 400 mg
      m(-2)cycle(-1). At 550 and 700 mg m(-2)cycle(-1)reversible dose-limiting
      neutropenia occurred. Other toxicities included mild fatigue, nausea and
      vomiting. No objective remission was seen. Pharmakokinetic analysis showed a
      terminal half-life of approximately 2 days. AUC and Cmax were related to dose;
      neutropenia correlated with AUC. The recommended dose for further phase II
      studies on this schedule is 400 mg m(-2)cycle(-1).

PMID- 10944597
TI  - A phase II study of temozolomide vs. procarbazine in patients with glioblastoma
      multiforme at first relapse.
AB  - A randomized, multicentre, open-label, phase II study compared temozolomide
      (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225
      patients with glioblastoma multiforme at first relapse. Primary objectives were
      to determine progression-free survival (PFS) at 6 months and safety for TMZ and
      PCB in adult patients who failed conventional treatment. Secondary objectives
      were to assess overall survival and health-related quality of life (HRQL). TMZ
      was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5
      days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125
      mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was
      assessed using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20
      (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met
      the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P
      = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a
      median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P =
      0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for
      PCB patients (P = 0.019). Freedom from disease progression was associated with
      maintenance of HRQL, regardless of treatment received. TMZ had an acceptable
      safety profile; most adverse events were mild or moderate in severity.

PMID- 10944599
TI  - The treatment of Wilms' tumour: results of the United Kingdom Children's cancer
      study group (UKCCSG) second Wilms' tumour study.
AB  - The aims of the UKW2 study were: (1) to further refine treatment for stage I and
      II favourable histology (FH) patients; (2) to consolidate the UKW1 results for
      stage III FH patients; (3) to improve the outlook for patients with inoperable
      primary tumours and those patients with stage IV and unfavourable histology
      disease. Treatment consisted of primary nephrectomy, wherever possible, followed
      by chemotherapy and radiotherapy, as dictated by stage and histology. Treatment
      was refined successfully for stage I and II FH patients. The 4-year event-free
      survival for these two groups was 94% and 91%, respectively. Stage III FH
      patients had a 4-year event free survival of 84%. The outlook for patients with
      clear cell sarcoma of the kidney is as good as for patients with favourable
      histology, whilst that for patients with anaplastic or rhabdoid variants remains
      poor. The outlook for the majority of children with Wilms' tumour is now
      excellent.

PMID- 10944600
TI  - Prognostic factors in patients with submucosal carcinoma of the oesophagus.
AB  - To clarify the prognostic factors in patients with submucosal carcinoma of the
      oesophagus, we examined the results of surgical treatment for 78 cases over the
      last decade. The clinicopathological factors including age, sex, location of the
      tumour, length of the tumour, histological differentiation, subclassification of
      depth, lymphatic or blood vessel invasion, intramural metastasis and lymph node
      metastasis were all analysed. Then the correlation between these factors and
      prognosis was investigated. As a result, significant differences were observed in
      the survival rates between the groups regarding lymphatic vessel invasion (P =
      0.0003), intramural metastasis (P = 0.0051) and lymph node metastasis (P =
      0.0026). According to a multivariate analysis, intramural metastasis (P = 0.0038,
      relative risk 9.17), vessel invasion (P = 0.0033, relative risk 6.25) and lymph
      node metastasis (P = 0.0187, relative risk 3.62) were found to be independent
      prognostic factors. The prognosis of the patients with at least one of these
      factors was significantly poorer than that without. The five-year survival rate
      of the patients without these factors was as good as that with mucosal carcinoma
      of the oesophagus. Based on our findings, vessel invasion, intramural metastasis
      and lymph node metastasis are thus considered to be significant prognostic
      factors in patients with submucosal carcinoma of the oesophagus.

PMID- 10944601
TI  - Prognostic factors in tongue cancer - relative importance of demographic,
      clinical and histopathological factors.
AB  - The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue
      have increased during the recent decades in the Western world. Much effort has
      been made to predict tumour behaviour, but we still lack specific prognostic
      indicators. The aim of our study was to evaluate the relative importance of the
      known demographic, clinical and histological factors in a homogeneous population
      based group of patients with SCC of the mobile tongue. The demographic and
      clinical factors were reviewed retrospectively from primary and tertiary care
      patient files. Histological prognostic factors were determined from pre-treatment
      biopsies. The TNM stage was found to be the most important prognostic factor. In
      particular, local spread outside the tongue rather than spread to regional lymph
      nodes was related to poor prognosis. Several demographic and histopathological
      factors were closely related to TNM stage. When the cases were divided into stage
      I-II carcinomas and stage III-IV carcinomas, it appeared that the patient's older
      age (> 65 years), a high malignancy score and an absence of overexpressed p53
      protein were associated with a poorer prognosis in stage I-II carcinomas. Such
      cases may require more aggressive treatment. Among patients with stage III-IV
      carcinomas, heavy use of alcohol was significantly associated with a poor disease
      specific survival time.

PMID- 10944602
TI  - Vascular endothelial growth factor (VEGF) expression is a prognostic factor for
      radiotherapy outcome in advanced carcinoma of the cervix.
AB  - The aim of the study was to evaluate VEGF expression in tumour biopsies as a
      prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A
      retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF
      expression was examined immunohistochemically in formalin-fixed, paraffin
      embedded biopsies using a widely available commercial antibody. A semi
      quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for
      increasing intensity of staining. High VEGF expression was associated with a poor
      prognosis. A univariate log rank analysis found a significant relationship with
      overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not
      local control (P = 0.23). There was no correlation between VEGF expression and
      disease stage, tumour differentiation, patient age, or tumour radiosensitivity
      (SF2). In a Cox multivariate analysis of survival VEGF expression was the most
      significant independent prognostic factor (P = 0.001). After allowing for VEGF
      only SF2 was a significant prognostic factor (P = 0.003). In conclusion,
      immunohistochemical analysis of VEGF expression is a highly significant and
      independent prognostic indicator of overall and metastasis-free survival for
      patients treated with radiotherapy for advanced carcinoma of the cervix. It is
      also a rapid and easy method that could be used in the clinical setting, to
      identify patients at high risk of failure with conventional radiotherapy who may
      benefit from novel approaches or chemoradiotherapy.

PMID- 10944603
TI  - Decreased expression of p57(KIP2)mRNA in human bladder cancer.
AB  - To identify targets of genetic and epigenetic alterations on chromosome 11p15.5
      in human bladder cancer, expression of the imprinted KIP2, IGF2 and H19 genes was
      studied by quantitative RT-PCR in 24 paired samples of urothelial carcinomas and
      morphologically normal mucosa obtained by cystectomy, and in bladder carcinoma
      cell lines. The most frequent alteration in tumour tissue was decreased
      expression of KIP2 identified in 9/24 (37%) specimens. Decreased IGF2 and H19
      mRNA levels were found in five (21%) and three (13%) tumours, respectively. One
      tumour each overexpressed IGF2 and H19. Loss of H19 expression was only found
      associated with loss of KIP2 expression, whereas decreased expression of IGF2
      mRNA occurred independently. Almost all bladder carcinoma cell lines showed
      significant changes in the expression of at least one gene with diminished
      expression of KIP2 mRNA as the most frequent alteration. IGF2 mRNA levels were
      diminished in several lines, but increased in others. The KIP2 gene could be an
      important target of genetic and epigenetic alterations in bladder cancer
      affecting the maternal chromosome 11p15.5. However, reminiscent of the situation
      in Wilms' tumours, expression of the IGF2 gene on the paternal chromosome can
      also be disturbed in bladder cancers.

PMID- 10944604
TI  - The association between atypical adenomatous hyperplasia and primary lung cancer.
AB  - Atypical adenomatous hyperplasia (AAH) has been suggested as the adenoma in an
      adenoma-carcinoma sequence in the lung periphery. From 1989-1998, we undertook a
      systematic, prospective search for AAH in lungs resected for cancer. AAH was
      found in 67 of 554 patients (12. 1%) with primary lung carcinoma (9.2% in male
      patients and 19.0% in females). AAH was found in lungs bearing adenocarcinoma
      (23.2%) more frequently than with large cell undifferentiated carcinoma (12.5%)
      or squamous carcinoma (3.3%). A greater percentage of females with adenocarcinoma
      had AAH (30.2%) than did males with adenocarcinoma (18.8%). Numbers of AAH ranged
      from 1-42 per patient and more patients had small numbers of AAH, although 12
      patients had 6 or more AAH foci. Larger numbers of AAH tended to be found in
      adenocarcinoma-bearing lungs. Ten of the 67 patients with AAH and primary lung
      carcinoma (15%) had multiple primary cancers (range 2-6), all of which were
      adenocarcinoma. Synchronous cancers were rare in lung tumour-bearing resections
      without AAH. Patients with AAH show no difference in post-operative survival to
      those without, for all stages of carcinoma and for Stage I disease alone. This
      study provides evidence for a strong association between atypical adenomatous
      hyperplasia and primary lung adenocarcinoma and lends weight to the AAH/adenoma
      carcinoma hypothesis.

PMID- 10944605
TI  - Enhanced expression of IFN-gamma mRNA in CD4(+)or CD8(+)tumour-infiltrating
      lymphocytes compared to peripheral lymphocytes in patients with renal cell
      cancer.
AB  - The mRNA expression of the cytokines IFN-gamma, IL-10 and TNF-alpha and the
      proapoptotic factor Fas ligand (FasL) was compared in freshly isolated CD4(+)and
      CD8(+)tumour-infiltrating lymphocytes (TIL) and simultaneously obtained
      autologous CD4(+)and CD8(+)peripheral blood lymphocytes (PBL) from 20 patients
      with renal cell carcinomas (RCC). TIL were isolated from mechanically
      disaggregated tumour material and PBL from peripheral blood by gradient
      centrifugation. The cells of the interphase were depleted from tumour cells with
      anti-human epithelial antigen magnetic beads and then positive selection was
      performed with anti-CD4 or anti-CD8 magnetic beads. In these pure lymphocyte
      preparations the constitutive expression of cytokine and FasL mRNAs was
      determined by using a PCR-assisted mRNA amplification assay. In the CD4(+)TIL
      from the 20 patients with RCC, levels of mRNAs encoding for IFN-gamma (P</=
      0.001), IL-10 (P</= 0.05), and FasL (P</= 0.001) were significantly higher than
      in the autologous CD4(+)PBL. Comparison of CD8(+)TIL and CD8(+)PBL revealed a
      significant higher expression of IFN-gamma (P</= 0.001), IL-10 (P</= 0.01) and
      FasL mRNAs (P</= 0.001) in the former. However, TNF-alpha mRNA levels were
      significantly lower in the CD8(+)TIL than in the CD8(+)PBL (P</= 0.05). These
      data reflect a general in vivo activation of RCC infiltrating lymphocytes in the
      tumour surrounding.

PMID- 10944606
TI  - Caspase-3-like activity determines the type of cell death following ionizing
      radiation in MOLT-4 human leukaemia cells.
AB  - Caspases, a family of cysteine proteases, play a central role in the pathways
      leading to apoptosis. Recently, it has been reported that a broad spectrum
      inhibitor of caspases, the tripeptide Z-VAD-fmk, induced a switch from apoptosis
      to necrosis in dexamethasone-treated B lymphocytes and thymocytes. As such a cell
      death conversion could increase the efficiency of radiation therapy and in order
      to identify the caspases involved in this cell death transition, we investigated
      the effects of caspase-3-related proteases inhibition in irradiated MOLT-4 cells.
      Cells were pretreated with Ac-DEVD-CHO, an inhibitor of caspase-3-like activity,
      and submitted to X-rays at doses ranging from 1 to 4 Gy. Our results show that
      the inhibition of caspase-3-like activity prevents completely the appearance of
      the classical hallmarks of apoptosis such as internucleosomal DNA fragmentation
      or hypodiploid particles formation and partially the externalization of
      phosphatidylserine. However, this was not accompanied by any persistent increase
      in cell survival. Instead, irradiated cells treated by this inhibitor exhibited
      characteristics of a necrotic cell death. Therefore, functional caspase-3
      subfamily not only appears as key proteases in the execution of the apoptotic
      process, but their activity may also influence the type of cell death following
      an exposure to ionizing radiation.

PMID- 10944607
TI  - Increased collagen production in fibroblasts cultured from irradiated skin and
      effect of TGF beta(1)- clinical study.
AB  - Fibrosis in normal tissues is a common and dose-limiting late complication of
      radiotherapy at many cancer sites, but its pathogenesis is poorly understood. We
      undertook a controlled study of the effect of irradiation on the collagen
      production of fibroblasts cultured from skin biopsies taken from patients
      undergoing radiotherapy treatment. Eight weeks after a single 8 Gy fraction using
      300 kV X-rays, five patients treated at the Royal Marsden Hospital underwent
      biopsy of the irradiated site and of the contralateral, unirradiated body site.
      Fibroblasts from irradiated and control, unirradiated sites were cultured in
      vitro, and collagen production rates were measured during a 48-hour incubation
      under standardized conditions and in the presence and absence of transforming
      growth factor beta(1)(TGF beta(1)), 1 ng/ml, using HPLC. Collagen production was
      elevated in cells cultured from irradiated skin; median collagen production rates
      61.16 pmoles hydroxyproline/10(5)cells/hour in irradiated cells, 39.78 pmoles
      hydroxyproline/10(5)cells/hour in unirradiated cells, P = 0.016 (Mann-Whitney U
      test). In fibroblasts from unirradiated sites, collagen production rates were
      increased by the addition of TGF beta(1); however, in three of the cell lines
      cultured from irradiated sites this effect of TGF beta(1)on collagen production
      was not observed.

PMID- 10944608
TI  - Effect of photodynamic therapy in combination with ionizing radiation on human
      squamous cell carcinoma cell lines of the head and neck.
AB  - Photodynamic therapy (PDT) is a promising treatment modality for head and neck,
      and other tumours, using drugs activated by light. A second generation drug, 5
      aminolaevulinic acid (5-ALA), is a precursor of the active photosensitizer
      protoporphyrin IX (PpIX) and has fewer side-effects and much more transient
      phototoxicity than previous photosensitizers. We have investigated the effect of
      5-ALA mediated PDT in combination with gamma-irradiation on the colony forming
      ability of several human head and neck tumour cell lines. The effect of
      treatments on the DNA cell cycle kinetics was also investigated. Our results
      indicate that the combination of 5-ALA mediated PDT and gamma-irradiation results
      in a level of cytotoxicity which is additive and not synergistic. 5-ALA mediated
      PDT had no discernible effect on DNA cell cycle distributions. gamma-irradiation
      induced cell cycle arrest in G2 did not enhance the phototoxicity of 5-ALA.

PMID- 10944609
TI  - Gene delivery to hypoxic cells in vitro.
AB  - Hypoxia in solid tumours has been correlated with poor prognosis and resistance
      to radiation and chemotherapy. Hypoxia is also a strong stimulus for gene
      expression. We previously proposed a gene therapy approach which exploits the
      presence of severe hypoxia in tumours for the induction of therapeutic genes.
      Hypoxic cells are known to have a reduced metabolic rate, transcription and
      translation. These facts may prevent gene transfer and therefore warranted
      further investigation. In this paper the feasibility of gene delivery in vitro
      under tumour conditions was demonstrated. DNA was delivered in vitro using a
      peptide-mediated non-viral system. Across a range of oxygen tensions and
      mammalian cell lines (including human tumour and endothelial cells) it was shown
      that hypoxic cells could be transfected. Transfection efficiencies varied
      depending on the level of hypoxia, cell characteristics and gene promoters used.
      An in vitro model of hypoxia/reoxygenation, designed to mimic the variable nature
      of tumour hypoxia, showed that hypoxic preconditioning and reoxygenation alone
      did not reduce transfection efficiency significantly; only chronic anoxia reduced
      transfection. The fact that neither intermediate hypoxia nor intermittent anoxia
      significantly reduced transfection is promising for future hypoxia-targeted gene
      therapy strategies.

PMID- 10944610
TI  - Met/HGF receptor modulates bcl-w expression and inhibits apoptosis in human
      colorectal cancers.
AB  - The met proto-oncogene is the tyrosine kinase growth factor receptor for
      hepatocyte growth factor. In the present study, we investigated the role of met
      expression on the modulation of apoptosis in colorectal tumours. The gene
      expressions of c-met and the anti-apoptotic bcl-2 family, including bcl-2, bcl
      x(L)and bcl-w, were analysed in human colorectal adenomas and adenocarcinomas by
      using a quantitative polymerase chain-reaction combined with reverse
      transcription. In seven of 12 adenomas and seven of 11 carcinomas, the c-met gene
      was overexpressed. The bcl-w, bcl-2 and bcl-x(L)genes were over-expressed in
      nine, five and six of 12 adenomas and in five, two and seven of 11 carcinomas,
      respectively. The c-met mRNA level in human colorectal adenomas and carcinomas
      was correlated with bcl-w but not with bcl-2 or with bcl-x(L)mRNA level. The
      administration of c-met-antisense oligonucleotides decreased Met protein levels
      in the LoVo human colon cancer cell line. In the case of c- met -antisense
      treated cells, apoptotic cell death induced by serum deprivation was more
      prominent, compared to control or c-met -nonsense-treated cells. Treatment with c
      met-antisense oligonucleotides inhibits the gene expression of bcl-w in LoVo
      cells. On the other hand, the gene expression of bcl-2 or bcl-x(L)was not
      affected by treatment with c-met-antisense oligonucleotides. These findings
      suggest that Met expression modulates apoptosis through bcl -w expression in
      colorectal tumours.

PMID- 10944611
TI  - Vascular architecture and hypoxic profiles in human head and neck squamous cell
      carcinomas.
AB  - Tumour oxygenation and vasculature are determinants for radiation treatment
      outcome and prognosis in patients with squamous cell carcinomas of the head and
      neck. In this study we visualized and quantified these factors which may provide
      a predictive tool for new treatments. Twenty-one patients with stage III-IV
      squamous cell carcinomas of the head and neck were intravenously injected with
      pimonidazole, a bioreductive hypoxic marker. Tumour biopsies were taken 2 h
      later. Frozen tissue sections were stained for vessels and hypoxia by fluorescent
      immunohistochemistry. Twenty-two sections of biopsies of different head and neck
      sites were scanned and analysed with a computerized image analysis system. The
      hypoxic fractions varied from 0.02 to 0.29 and were independent from T- and N
      classification, localization and differentiation grade. No significant
      correlation between hypoxic fraction and vascular density was observed. As a
      first attempt to categorize tumours based on their hypoxic profile, three
      different hypoxia patterns are described. The first category comprised tumours
      with large hypoxic, but viable, areas at distances even greater than 200
      micrometer from the vessels. The second category showed a typical band-like
      distribution of hypoxia at an intermediate distance (50-200 micrometer) from the
      vessels with necrosis at greater distances. The third category demonstrated
      hypoxia already within 50 micrometer from the vessels, suggestive for acute
      hypoxia. This method of multiparameter analysis proved to be clinically feasible.
      The information on architectural patterns and the differences that exist between
      tumours can improve our understanding of the tumour micro-environment and may in
      the future be of assistance with the selection of (oxygenation modifying)
      treatment strategies.

PMID- 10944612
TI  - Influence of tumour size on uptake of(111)ln-DTPA-labelled pegylated liposomes in
      a human tumour xenograft model.
AB  - The relationship between tumour size and uptake of(111)In-DTPA-labelled pegylated
      liposomes has been examined in a human head and neck cancer xenograft model in
      nude mice. The mean tumour uptake of(111)In-labelled pegylated liposomes at 24
      hours was 7.2 +/- 6.6% ID/g. Liposome uptake for tumours < 0.1 g, 0.1-1.0 g and >
      1.0 g was 15.1 +/- 10.8, 5.9 +/- 2.2 and 3.0 +/- 1.3% ID/g, respectively. An
      inverse correlation between tumour weight and liposome uptake was observed by
      both Spearman's rank correlation test (r(s)= - 0.573, P< 0.001) and Pearson's
      correlation coefficient (r(s)= - 0.555, P< 0.001). For 18 tumours with
      macroscopic central necrosis, the ratio of uptake in the tumour rim relative to
      the necrotic tumour core was 11.2 +/- 6.4. Measurement of tumour vascular volume
      for tumours of various sizes revealed an inverse correlation between tumour
      weight and tumour vascular volume (Spearman's rank correlation test, r(s)= -
      0.598, P< 0.001), consistent with poor or heterogeneous vascularization of larger
      tumours. These data have important implications for the clinical application of
      pegylated liposome targeted strategies for solid cancers which are discussed in
      detail.

PMID- 10944613
TI  - Smoking and drinking cessation and the risk of oesophageal cancer.
AB  - In a case-control study from Italy and Switzerland with 404 oesophageal cancer
      cases and 1070 hospital controls, the risk of oesophageal cancer declined with
      time since cessation of smoking or drinking, and was significantly reduced (odds
      ratio = 0.11) 10 or more years after cessation of both habits.

PMID- 10944614
TI  - A pooled analysis of magnetic fields and childhood leukaemia.
AB  - Previous studies have suggested an association between exposure to 50-60 Hz
      magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis
      based on individual records from nine studies, including the most recent ones.
      Studies with 24/48-hour magnetic field measurements or calculated magnetic fields
      were included. We specified which data analyses we planned to do and how to do
      them before we commenced the work. The use of individual records allowed us to
      use the same exposure definitions, and the large numbers of subjects enabled more
      precise estimation of risks at high exposure levels. For the 3203 children with
      leukaemia and 10 338 control children with estimated residential magnetic field
      exposures levels < 0.4 microT, we observed risk estimates near the no effect
      level, while for the 44 children with leukaemia and 62 control children with
      estimated residential magnetic field exposures >/= 0.4 microT the estimated
      summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for
      potential confounding variables did not appreciably change the results. For North
      American subjects whose residences were in the highest wire code category, the
      estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence
      in the combined data for the existence of the so-called wire-code paradox. In
      summary, the 99.2% of children residing in homes with exposure levels < 0.4
      microT had estimates compatible with no increased risk, while the 0.8% of
      children with exposures >/= 0.4 microT had a relative risk estimate of
      approximately 2, which is unlikely to be due to random variability. The
      explanation for the elevated risk is unknown, but selection bias may have
      accounted for some of the increase.

PMID- 10944615
TI  - Seasonal variations in the diagnosis of childhood cancer.

PMID- 10944617
TI  - JAMA 100 years ago: KERATOLYSIS OR "SKIN-SHEDDING."

PMID- 10944616
TI  - Seasonal variations in the diagnosis of childhood cancer - reply

PMID- 10944618
TI  - Management changes in primary hyperparathyroidism.

PMID- 10944619
TI  - Publishers debate future of online journals.

PMID- 10944620
TI  - When a bioweapon strikes, who will be in charge?

PMID- 10944621
TI  - A good word--in part--now offered for H pylori.

PMID- 10944622
TI  - Widely used spermicide may increase, not decrease, risk of HIV transmission.

PMID- 10944624
TI  - Quick uptakes: gene protects kidneys

PMID- 10944623
TI  - From the Surgeon General.

PMID- 10944625
TI  - Quick uptakes: advisory on contraceptives

PMID- 10944626
TI  - Quick uptakes: powerful poetry

PMID- 10944627
TI  - Quick uptakes: pancreatitis pain relief

PMID- 10944628
TI  - Breastfeeding in women with HIV.

PMID- 10944629
TI  - Breastfeeding in women with HIV.

PMID- 10944630
TI  - Breastfeeding in women with HIV

PMID- 10944631
TI  - Preparticipation cardiovascular screening for young athletes.

PMID- 10944632
TI  - Preparticipation cardiovascular screening for young athletes.

PMID- 10944633
TI  - Preparticipation cardiovascular screening for young athletes

PMID- 10944634
TI  - Treatment of poststroke depression.

PMID- 10944635
TI  - Treatment of poststroke depression.

PMID- 10944636
TI  - Treatment of poststroke depression

PMID- 10944638
TI  - Blood pressure levels and risk of stroke in elderly patients

PMID- 10944637
TI  - Blood pressure levels and risk of stroke in elderly patients.

PMID- 10944639
TI  - Long-term obligations to human subjects in clinical trials.

PMID- 10944640
TI  - Utility of endoscopic screening for upper gastrointestinal adenocarcinoma.

PMID- 10944641
TI  - Ondansetron for reduction of drinking among biologically predisposed alcoholic
      patients: A randomized controlled trial.
AB  - CONTEXT: Early-onset alcoholism differs from late-onset alcoholism by its
      association with greater serotonergic abnormality and antisocial behaviors. Thus,
      individuals with early-onset alcoholism may be responsive to treatment with a
      selective serotonergic agent. OBJECTIVE: To test the hypothesis that drinking
      outcomes associated with early vs late-onset alcoholism are differentially
      improved by the selective 5-HT(3) (serotonin) antagonist ondansetron. DESIGN:
      Double-blind, randomized, placebo-controlled clinical trial. SETTINGS: University
      of Texas Health Science Center in Houston (April 1995-June 1998) and University
      of Texas Health Science Center in San Antonio (July 1998-December 1999).
      PARTICIPANTS: A total of 321 patients with diagnosed alcoholism (mean age, 40.6
      years; 70.5% male; 78.6% white) were enrolled, 271 of whom proceeded to
      randomization. INTERVENTIONS: After 1 lead-in week of single-blind placebo,
      patients were randomly assigned to receive 11 weeks of treatment with
      ondansetron, 1 microg/kg (n = 67), 4 microg/kg (n = 77), or 16 microg/kg (n = 71)
      twice per day; or identical placebo (n = 56). All patients also participated in
      weekly standardized group cognitive behavioral therapy. MAIN OUTCOME MEASURES:
      Self-reported alcohol consumption (drinks per day, drinks per drinking day,
      percentage of days abstinent, and total days abstinent per study week); and
      plasma carbohydrate deficient transferrin (CDT) level, an objective and sensitive
      marker of transient alcohol consumption. RESULTS: Patients with early-onset
      alcoholism who received ondansetron (1, 4, and 16 microg/kg twice per day)
      compared with those who were administered placebo, had fewer drinks per day
      (1.89, 1.56, and 1.87 vs 3.30; P =.03, P =.01, and P =.02, respectively) and
      drinks per drinking day (4.75, 4.28, and 5.18 vs 6.90; P =.03, P =.004, and P
      =.03, respectively). Ondansetron, 4 microg/kg twice per day, was superior to
      placebo in increasing percentage of days abstinent (70.10 vs 50.20; P =.02) and
      total days abstinent per study week (6.74 vs 5.92; P =.03). Among patients with
      early-onset alcoholism, there was a significant difference in the mean log CDT
      ratio between those who received ondansetron (1 and 4 microg/kg twice per day)
      compared with those who received the placebo (-0.17 and -0.19 vs 0.12; P =.03 and
      P =.01, respectively). CONCLUSION: Our results suggest that ondansetron
      (particularly the 4 microg/kg twice per day dosage) is an effective treatment for
      patients with early-onset alcoholism, presumably by ameliorating an underlying
      serotonergic abnormality. JAMA. 2000;284:963-971

PMID- 10944642
TI  - Low bone mineral density and risk of fracture in white female nursing home
      residents.
AB  - CONTEXT: Low bone mineral density (BMD) is a strong risk factor for fracture in
      community-dwelling white women, but the relationship in white female nursing home
      residents, for whom fracture rates are highest, is less clear. OBJECTIVE: To
      assess the relative contribution of low BMD to fracture risk in nursing home
      residents. DESIGN: Prospective cohort study with baseline data collected April
      1995 to June 1997, with 18 months of follow-up. SETTING: Forty-seven randomly
      selected nursing homes in Maryland. PATIENTS: A total of 1427 white female
      nursing home residents aged 65 years or older. MAIN OUTCOME MEASURE: Documented
      osteoporotic fracture occurring during follow-up as a function of baseline BMD
      measurements higher vs lower than the median, and after controlling for
      demographic, functional, cognitive, psychosocial, and medical factors. RESULTS: A
      total of 223 osteoporotic fractures occurred among 180 women. Low BMD and
      transfer independence were significant independent risk factors for fracture in
      this nursing home sample (P<.001) and the 2 factors acted synergistically (P
      =.06) to further increase fracture risk. Compared with women whose BMD was higher
      than the median (0. 296 g/cm(2)), those whose BMD was lower than the median had
      an unadjusted hazard ratio for risk of fracture of 2.1 (95% confidence interval
      [CI], 1.5-2.8); women who were independent in transfer had a hazard ratio of 1.6
      (95% CI, 1.2-2.2) compared with women dependent in transfer. Among residents
      independent in transfer, those with BMD below the median had a more than 3-fold
      increase in fracture risk compared with those with higher BMD (unadjusted hazard
      ratio, 3.1; 95% CI, 2.2-4.4). Among residents dependent in transfer, those with
      BMD below the median had a 60% increase in fracture risk (unadjusted hazard
      ratio, 1.6; 95% CI, 1.1-2.3). Adjustment for covariates did not alter the BMD
      fracture relationship. CONCLUSIONS: Our data indicate that low BMD and
      independence in transfer are significant predictors of osteoporotic fracture in
      white female nursing home residents. JAMA. 2000;284:972-977

PMID- 10944643
TI  - Association between administration of hepatitis B vaccine at birth and completion
      of the hepatitis B and 4:3:1:3 vaccine series.
AB  - CONTEXT: The association between infant age at initiation of hepatitis B
      vaccination and completion of the 3-dose hepatitis B vaccination series is
      unclear. OBJECTIVE: To assess the association between administration of the first
      dose of hepatitis B vaccine within 7 days of birth and completion of the
      hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria
      tetanus-pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles-containing
      vaccine, and 3 doses of Haemophilus influenzae type b vaccine). DESIGN, SETTING,
      AND PARTICIPANTS: Analysis of data from the 1998 National Immunization Survey, a
      random-digit-dialing telephone survey (n = 34,480 completed interviews) of
      parents of children aged 19 to 35 months from 50 states and 28 selected urban
      areas in the United States that included a provider record check mail survey.
      MAIN OUTCOME MEASURES: Percentage of infants who received at least 3 doses of
      hepatitis B vaccine and percentage who received the 4:3:1:3 vaccine series, by
      age at receipt of the first dose of hepatitis B vaccine. RESULTS: Overall, 86.9%
      of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis
      B vaccine, and 79.9% completed the 4:3:1:3 vaccine series. Multivariate analysis
      indicated that, compared with children who received the first hepatitis B vaccine
      dose within 7 days of birth, odds ratios (ORs) for not completing the 3-dose
      hepatitis B vaccine series among children who received the first dose at 8 to 41
      days, 42 to 91 days, 92 to 182 days, 183 to 273 days, and 274 or more days of age
      were 2.4 (95% confidence interval [CI], 2.0-3.0), 7.8 (95% CI, 6.5-9.3), 9.6 (95%
      CI, 7.0-13. 3), 18.3 (95% CI, 12.0-28.0), and 46.6 (95% CI, 33.7-64.5),
      respectively; ORs for not completing the 4:3:1:3 vaccine series among these same
      groups were 1.0 (95% CI, 0.8-1.1), 1.0 (95% CI, 0. 8-1.1), 1.7 (95% CI, 1.3-2.3),
      3.8 (95% CI, 2.6-5.6), and 4.0 (95% CI, 2.9-5.5), respectively. CONCLUSION:
      Administration of the first dose of hepatitis B vaccine at birth is associated
      with increased likelihood of completion of the hepatitis B vaccination series.
      JAMA. 2000;284:978-983

PMID- 10944644
TI  - Quality of care for patients with rheumatoid arthritis.
AB  - CONTEXT: Patients with rheumatoid arthritis are at risk for substantial morbidity
      because of their arthritis and premature mortality due to comorbid diseases.
      However, little is known about the quality of the health care that these patients
      receive. OBJECTIVE: To assess the quality of the health care that rheumatoid
      arthritis patients receive for their arthritis, comorbid diseases, and health
      care maintenance and to determine the effect of patterns of specialty care on
      quality. DESIGN, SETTING, AND PARTICIPANTS: Historical cohort study of 1355 adult
      rheumatoid arthritis patients enrolled in the fee-for-service or discounted fee
      for-service plans of a nationwide US insurance company. Patients were identified
      and followed up through administrative data between 1991 and 1995. MAIN OUTCOME
      MEASURES: Quality scores for arthritis, comorbid disease, and health care
      maintenance were developed from performance on explicit process measures that
      related to each of these domains and described the percentage of indicated health
      care processes performed within each domain during each person-year of the study.
      RESULTS: During 4598 person-years of follow-up, quality scores were 62% (95%
      confidence interval [CI], 61%-64%) for arthritis care, 52% (95% CI, 49%-55%) for
      comorbid disease care, and 42% (95% CI, 40%-43%) for health care maintenance.
      Across domains, care patterns including relevant specialists yielded performance
      scores 30% to 187% higher than those that did not (P<.001) and 45% to 67% of
      person-years were associated with patterns of care that did not include a
      relevant specialist. Presence of primary care without specialty care yielded
      health care maintenance scores that were 43% higher than those for patterns that
      included neither primary nor relevant specialty care (P<.001). CONCLUSIONS: In
      this population, health care quality appears to be suboptimal for arthritis,
      comorbid disease, and health care maintenance. Patterns of care that included
      relevant specialists were associated with substantially higher quality across all
      domains. Patterns that included generalists were associated with substantially
      higher quality health care maintenance than patterns that included neither a
      generalist nor a relevant specialist. The optimal roles of primary care
      physicians and specialists in the care of patients with complex conditions should
      be reassessed. JAMA. 2000;284:984-992

PMID- 10944645
TI  - Neurological development of 5-year-old children receiving a low-saturated fat,
      low-cholesterol diet since infancy: A randomized controlled trial.
AB  - CONTEXT: Early childhood introduction of nutritional habits aimed at
      atherosclerosis prevention is compatible with normal growth, but its effect on
      neurological development is unknown. OBJECTIVE: To analyze how parental
      counseling aimed at keeping children's diets low in saturated fat and cholesterol
      influences neurodevelopment during the first 5 years of life. DESIGN: Randomized
      controlled trial conducted between February 1990 and November 1996. SETTING:
      Outpatient clinic of a university department in Turku, Finland. PARTICIPANTS: A
      total of 1062 seven-month-old infants and their parents, recruited at well-baby
      clinics between 1990 and 1992. At age 5 years, 496 children still living in the
      city of Turku were available to participate in neurodevelopmental testing.
      INTERVENTION: Participants were randomly assigned to receive individualized
      counseling aimed at limiting the child's fat intake to 30% to 35% of daily
      energy, with a saturated:monounsaturated:polyunsaturated fatty acid ratio of
      1:1:1 and a cholesterol intake of less than 200 mg/d (n = 540) or usual health
      education (control group, n = 522). MAIN OUTCOME MEASURES: Nutrient intake, serum
      lipid concentrations, and neurological development at 5 years, among children in
      the intervention vs control groups. RESULTS: Absolute and relative intakes of
      fat, saturated fatty acids, and cholesterol among children in the intervention
      group were markedly less than the respective values of control children. Mean
      (SD) percentages of daily energy at age 5 years for the intervention vs control
      groups were as follows: for total fat, 30.6% (4.5%) vs 33.4% (4.4%) (P<. 001);
      and for saturated fat, 11.7% (2.3%) vs 14.5% (2.4%) (P<.001). Mean intakes of
      cholesterol were 164.2 mg (60.1 mg) and 192.5 mg (71. 9 mg) (P<.001) for the
      intervention and control groups, respectively. Serum cholesterol concentrations
      were continuously 3% to 5% lower in children in the intervention group than in
      children in the control group. At age 5 years, mean (SD) serum cholesterol
      concentration of the intervention group was 4.27 (0.63) mmol/L (165 [24] mg/dL)
      and of the control group, 4.41 (0.74) mmol/L (170 [29] mg/dL) (P =.04).
      Neurological development of children in the intervention group was at least as
      good as that of children in the control group. Relative risks for children in the
      intervention group to fail tests of speech and language skills, gross motor
      functioning plus perception, and visual motor skills were 0.95 (90% confidence
      interval [CI], 0.60-1.49), 0.95 (90% CI, 0.58-1.55), and 0.65 (90% CI, 0.39
      1.08), respectively (P =.85,.86, and.16, respectively, vs control children).
      CONCLUSION: Our data indicate that repeated child-targeted dietary counseling of
      parents during the first 5 years of a child's life lessens age-associated
      increases in children's serum cholesterol and is compatible with normal
      neurological development. JAMA. 2000;284:993-1000

PMID- 10944646
TI  - Appropriateness of rabies postexposure prophylaxis treatment for animal
      exposures. Emergency ID Net Study Group.
AB  - CONTEXT: Rabies postexposure prophylaxis (RPEP) treatments and associated costs
      have increased in the United States. The extent to which RPEP use is consistent
      with guidelines is not well understood. OBJECTIVE: To characterize animal
      contacts and determine the frequency and factors associated with inappropriate
      RPEP use. DESIGN, SETTING, AND PATIENTS: Prospective case series study of
      patients presenting with an animal exposure-related complaint from July 1996 to
      September 1998 at 11 university-affiliated, urban emergency departments (the
      Emergency ID Net). MAIN OUTCOME MEASURES: Exposure type, circumstances, and RPEP
      use (appropriateness defined by local public health departments). RESULTS: Of
      2030 exposures, 1635 (81%) were to dogs; 268 (13%) to cats; 88 (4%) to
      rodents/rabbits; 10 (0. 5%) to raccoons; 5 (0.2%) to bats; and 24 (1.2%) to other
      animals. Among those exposed, 136 (6.7%) received RPEP after dog (95), cat (21),
      raccoon (8), bat (4), or other animal (8) exposures. Use of RPEP varied by site
      (range, 0%-27.7% of exposures), with most frequent use reported at sites in the
      eastern United States. Management was considered appropriate in 1857 exposures
      (91.5%). Use of RPEP was considered inappropriate in 54 cases (40% of those in
      which it was given), owing to factors including animal availability for
      observation and exposure in a low-endemicity area. Rabies postexposure
      prophylaxis was considered inappropriately withheld from 119 cases (6.3% of those
      not receiving RPEP), often because a domestic animal was unavailable for
      observation or testing. CONCLUSION: These results suggest that use of RPEP is
      often inappropriate. Greater compliance with current guidelines would increase
      RPEP use. Physician education, improved coordination with public health
      officials, and clarification of RPEP guidelines could optimize use of this
      expensive resource. JAMA. 2000;284:1001-1007

PMID- 10944647
TI  - Preoperative radiotherapy for resectable rectal cancer: A meta-analysis.
AB  - CONTEXT: The benefit of adjuvant radiotherapy for resectable rectal cancer has
      been extensively studied, but data on survival are still equivocal despite a
      reduction in the rate of local recurrence. OBJECTIVE: To assess the effectiveness
      of preoperative radiotherapy followed by surgery in the reduction of overall and
      cancer-related mortality and in the prevention of local recurrence and distant
      metastases. DATA SOURCES: Computerized bibliographic searches of MEDLINE and
      CANCERLIT (1970 to December 1999), including non-English sources, were
      supplemented with hand searches of reference lists. The medical subject headings
      used were rectal cancer, radiotherapy, surgery, RCT, randomized, and clinical
      trial. STUDY SELECTION: Studies were included if they were randomized controlled
      trials (RCTs) comparing preoperative radiotherapy plus surgery with surgery alone
      and if they included patients with resectable histologically proven rectal
      adenocarcinoma, without metastatic disease. Fourteen RCTs were analyzed. DATA
      EXTRACTION: Data on population, intervention, and outcomes were extracted from
      each RCT according to the intention-to-treat method by 3 independent observers
      and combined using the DerSimonian and Laird method. DATA SYNTHESIS: Radiotherapy
      plus surgery compared with surgery alone significantly reduced the 5-year overall
      mortality rate (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.72-0.98; P
      =.03), cancer-related mortality rate (OR, 0.71; 95% CI, 0.61-0.82; P<.001), and
      local recurrence rate (OR, 0.49; 95% CI, 0.38-0.62; P<.001). No reduction was
      observed in the occurrence of distant metastases (OR, 0.93; 95% CI, 0.73-1.18; P
      =.54). CONCLUSIONS: In patients with resectable rectal cancer, preoperative
      radiotherapy significantly improved overall and cancer-specific survival compared
      with surgery alone. The magnitude of the benefit is relatively small and criteria
      are needed to identify patients most likely to benefit from adjuvant
      radiotherapy. JAMA. 2000;284:1008-1015

PMID- 10944648
TI  - Medications for alcohol dependence--new vistas.

PMID- 10944649
TI  - Bone health in nursing home residents.

PMID- 10944650
TI  - A study of patient clues and physician responses in primary care and surgical
      settings.
AB  - CONTEXT: Patients often present clues (direct or indirect comments about personal
      aspects of their lives or their emotions) during conversations with their
      physicians. These clues represent opportunities for physicians to demonstrate
      understanding and empathy and thus, to deepen the therapeutic alliance that is at
      the heart of clinical care. A paucity of information exists regarding how
      physicians address the psychological and social concerns of patients. OBJECTIVES:
      To assess how patients present clues and how physicians respond to these clues in
      routine primary care and surgical settings. DESIGN, SETTING, AND PARTICIPANTS:
      Descriptive, qualitative study of 116 randomly selected routine office visits to
      54 primary care physicians and 62 surgeons in community-based practices in Oregon
      and Colorado, audiotaped and transcribed in 1994. MAIN OUTCOME MEASURES:
      Frequency of presentation of clues by patients during office visits, nature
      (emotional vs social) and content of clues, and nature of physician responses to
      clues, coded as positive or missed opportunity. RESULTS: Fifty-two percent and
      53% of the visits in primary care and surgery, respectively, included 1 or more
      clues. During visits with clues, the mean number of clues per visit was 2.6 in
      primary care and 1.9 in surgery. Patients initiated approximately 70% of clues,
      and physicians initiated 30%. Seventy-six percent of patient-initiated clues in
      primary care settings and 60% in surgical settings were emotional in nature. In
      surgery, 70% of emotional clues related to patients' feelings about their
      biomedical condition, while in primary care, emotional clues more often related
      to psychological or social concerns (80%) in patients' lives. Physicians
      responded positively to patient emotions in 38% of cases in surgery and 21% in
      primary care, but more frequently they missed opportunities to adequately
      acknowledge patients' feelings. Visits with missed opportunities tended to be
      longer than visits with a positive response. CONCLUSION: This study suggests that
      physicians in both primary care and surgery can improve their ability to respond
      to patient clues even in the context of their busy clinical practices. JAMA.
      2000;284:1021-1027

PMID- 10944651
TI  - Attention-deficit/hyperactivity disorder overview. Historical perspective,
      current controversies, and future directions.
AB  - There have been "modern" descriptions of ADHD in the medical literature since
      1902. Despite the burgeoning growth of information about the cause,
      pathophysiology, and effective treatments of the disorder, ADHD has been
      particularly steeped in controversy, especially regarding the use of medication
      (safety, efficacy, use or overuse, and concerns about medication treatment of
      preschool children). Changing diagnostic criteria, evolving conceptualizations of
      the disorder, and international differences in diagnosis, have enhanced and
      complicated ongoing research and understanding of the disorder. The recent
      Multimodal Treatment Study of Children with ADHD, a large, multisite study
      comparing efficacy of behavioral, medication, and combined treatments, and a
      recent NIH Consensus Conference on ADHD, represent true advances in the
      scientific understanding of the disorder and its treatment.

PMID- 10944652
TI  - Assessment and diagnosis of attention-deficit/hyperactivity disorder.
AB  - ADHD is the most common psychiatric disorder of childhood (3% to 5% of children)
      with continued morbidity into adolescence (85%) and adulthood (50% to 70%). It is
      a condition associated with widespread significant impairment in academic,
      occupational, social, and emotional functioning. It is also a condition with a
      broad extensive differential diagnosis as well as a high rate of comorbidity.
      There is no diagnostically definitive test for ADHD. Therefore, assessments for
      ADHD need to be comprehensive and should involve multiple domains, informants,
      methods, and settings. The comprehensive assessment needs to determine whether
      the subject has ADHD or another disorder. Thus, evaluation of various organic
      conditions, functional disorders, developmental status, situational,
      environmental, and family problems should all be explored. The clinical interview
      of the child and family is one of the cornerstones of the assessment process. A
      comprehensive medical history and examination, psychoeducational tests, and
      school-related evaluation, as well as a view of the child's social and emotional
      functioning, are also crucial. A wide array of rating scales, tests, and measures
      have been developed (see Table 1) to aid in the systematic standardized
      assessment of the various deficits associated with ADHD. None of these tests is
      definitive, however. Recent development of tests of executive functioning,
      neuroimaging, and genetics may provide more exact diagnostic guidelines in the
      future. Current DSM-IV criteria are phenomenologic rather than etiologic and are
      much more relevant and appropriate for children with ADHD compared with
      adolescents and adults. A comprehensive assessment involving various domains of
      functioning (academic, social, emotional, physical, and familial) provide not
      only more accurate diagnosis but also directions as to what difficulties exist
      and what multifaceted treatment plan is needed to produce current improvement and
      long-term positive outcome.

PMID- 10944653
TI  - Attention-deficit/hyperactivity disorder, predominantly inattentive subtype.
AB  - This article reviews research on the DSM-IV attention deficit/hyperactivity
      disorder inattentive (ADHD/IA) subtype. Data examining demographic
      characteristics, comorbidity, social functioning, and cognitive/attentional
      components are presented. Children with ADHD/IA show different patterns of
      demographic characteristics and comorbid symptomatology than those with ADHD/C,
      with suggestive evidence that they may differ in attentional style, as well. The
      implications of these results for treatment planning are discussed, along with
      suggestions that future research further examine attentional components,
      mechanisms contributing to impairment domains, and the role of sluggish cognitive
      tempo.

PMID- 10944654
TI  - Attention-deficit/hyperactivity disorder in adult life.
AB  - Many children and adolescents with ADHD become adults with ADHD. The clinical
      picture may be modified from that seen with youth; however, the hyperactivity,
      inattention, and impulsivity persist. These behaviors affect the individual in
      his or her education, work, relationship, and home settings. If this adult had
      learning disabilities as a child and adolescent, they will continue into
      adulthood. Many of the emotional, behavioral, and social problems of the past
      continue as well. If the child or adolescent with ADHD is identified early and
      treated properly throughout the school years, fewer secondary problems are
      carried into adulthood. If not identified early or if treated during childhood
      and not during adolescence, a greater number of emotional, behavioral, and social
      problems can occur in the adult. Identification of ADHD in adulthood is critical.
      Treatment with medications and with psychosocial interventions is essential.
      Educational, individual, and career counseling may be of significant importance.
      The consequence of missing this diagnosis or of not addressing the problems often
      related to ADHD is a less than functional and successful adult.

PMID- 10944655
TI  - Patterns of psychiatric comorbidity with attention-deficit/hyperactivity
      disorder.
AB  - Attention deficit/hyperactivity disorder (ADHD) is frequently comorbid with a
      variety of psychiatric disorders. These disorders include oppositional defiant
      (ODD) and conduct disorders (CD), and affective, anxiety, and learning disorders.
      Studies which have examined the comorbidity of these disorders with ADHD are
      reviewed. ADHD and ADHD with CD seem to be distinct subtypes; children with
      ADHD/CD are at higher risk of antisocial personality as adults. Coexisting
      anxiety may attenuate impulsivity in ADHD. Studies examining stimulant response
      in children with ADHD/anxiety have recently yielded conflicting results. Anxiety
      and ADHD seem to be inherited independently. The prevalence of major depressive
      disorder (MDD) and bipolar disorder among children with ADHD is controversial,
      but there clearly exists a subgroup of severely emotionally labile children with
      ADHD who present serious management issues for the clinician. About 20% to 25% of
      children with ADHD meet criteria for a learning disorder (LD), but LD seems to be
      independent of ADHD.

PMID- 10944656
TI  - Epidemiology of ADHD in school-age children.
AB  - Attention-Deficit/Hyperactivity Disorder is a relatively common condition of
      childhood onset and is of significant public health concern. Over the past two
      decades there have been 19 community-based studies offering estimates of
      prevalence ranging from 2% to 17%. The dramatic differences in these estimates
      are due to the choice of informant, methods of sampling and data collection, and
      the diagnostic definition. This article provides a critical review of the
      community-based studies on the prevalence of ADHD in children and adolescents.
      Based on the 19 studies reviewed, the best estimate of prevalence is 5% to 10% in
      school-aged children. The review also examines age and gender effects on the
      frequency of ADHD. The article closes with a discussion of psychosocial
      correlates and patterns of comorbidity in ADHD.

PMID- 10944657
TI  - ADHD: current concepts on etiology, pathophysiology, and neurobiology.
AB  - As cognitive neuroscience and developmental neurobiology advance, it is important
      that these advances be applied to the study of children and childhood disorders.
      Basic and pathophysiologic studies of the many forms of ADHD and possible causes,
      and studies of genes and gene environment interactions, are critical for an
      adequate understanding of this heterogeneous disorder. To date, most studies seem
      to have implicitly assumed that ADHD was immutable and all inborn, perhaps in
      part because of the high heritabilities. It is hoped that the next generation of
      research and researchers will tackle these formidable challenges, undertake the
      necessary longitudinal studies of early attention development and regulation, and
      link these studies to basic neuroscience research in animal models using the new
      tools available through molecular genetics and neuroimaging.

PMID- 10944658
TI  - The stimulants revisited.
AB  - Stimulants are the most often prescribed psychotropics in children and
      adolescents, used generally for the treatment of attention deficit/hyperactivity
      disorder (ADHD). In this article the authors summarize the literature on
      prevalence of usage, neurobiology, and pharmacology of the stimulants. Recent
      studies on the use of stimulants in special ADHD populations including
      preschoolers and adults, and co-occurring neurologic, psychiatric, and substance
      use disorders are cited. Clinical guidelines for the management of individuals
      receiving the stimulants are offered, and treatment strategies delineated for
      ADHD subjects with comorbidity and medication-induced adverse effects are
      discussed.

PMID- 10944659
TI  - Pharmacologic alternatives to psychostimulants for the treatment of attention
      deficit/hyperactivity disorder.
AB  - Alternatives to psychostimulants are now a routine part of the pharmacologic
      treatment of ADHD. Bupropion and most tricyclic antidepressants are sound options
      for managing core behavioral symptoms and, to some extent, cognitive symptoms.
      Alpha 2 adrenergic agonists can moderately reduce hyperactivity and impulsivity.
      Certain effective agents, such as desipramine, carbamazepine, neuroleptics,
      monoamine oxidase inhibitors, are clinically inadvisable in most cases. Lithium,
      benzodiazepines, antihistaminic sedatives, and buspirone are potentially
      detrimental. Venlafaxine and beta-adrenergic blockers seem potentially promising.
      Significant new options include norepinephrine reuptake inhibitors, such as
      reboxetine and tomoxetine, and possibly selective dopamine agonists. Central
      anticholinesterases, such as donepezil, may improve core ADHD symptoms and
      perhaps some associated features that psychostimulants do not--particularly
      organizational capacity and possibly other executive functions. The potential for
      bupropion to treat amotivational features should be investigated.

PMID- 10944660
TI  - Psychoeducational interventions for children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) are at risk for
      impaired functioning in most areas related to school success. Despite the
      benefits of psychostimulants and other medications to alleviate problem behaviors
      associated with ADHD, these therapies are unable to completely ameliorate
      behavior problems for all children with this disorder. Additionally, whereas
      pharmacologic therapies do impact behavioral functioning they have not been shown
      to improve academic achievement. Therefore, attention needs to be directed toward
      psychoeducational interventions and their ability to increase the successful
      functioning of children with ADHD. The purpose of this article is to highlight
      some of the most prominent and empirically validated classroom intervention
      strategies for children with ADHD. Additionally, this article discusses the
      importance of choosing psychoeducational interventions based on functional
      assessment data. Finally, this article describes progress monitoring strategies
      that should be used to determine the efficacy of intervention strategies.

PMID- 10944661
TI  - Psychosocial interventions. Individual psychotherapy with the child, and family
      interventions.
AB  - Research concerning ADHD and cost-effective and efficacious treatments of the
      core deficits and concomitant functional impairments is burgeoning. Substantial
      gains have been made in elucidating effective treatment modalities for the
      complex neuropsychiatric disorder of ADHD. Much remains to be investigated in
      order to gain a more thorough understanding of the differential contributions of
      psychosocial and medication treatments to the long-term outcome of this complex
      disorder.

PMID- 10944662
TI  - Behavior modification.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a chronic and substantially
      impairing disorder. This means that treatment must also be chronic and
      substantial. Behavior Modification, and in many cases, the combination of
      behavior modification and stimulant medication, is a valid, useful treatment for
      reducing the pervasive impairment experienced by children with ADHD. Based on the
      research evidence reviewed, behavior modification should be the first line of
      treatment for children with ADHD.

PMID- 10944663
TI  - Interventions to enhance social competence.
AB  - Social Impairment associated with attention deficit/hyperactivity disorder (ADHD)
      is difficult to treat. Stimulant treatment often improves social functioning, but
      rarely results in normalization. Behavioral approaches to improving social skills
      have progressed from unimodal techniques (contingency management) to packages
      that may combine multiple cognitive and behavioral techniques targeted directly
      to children and mediated by parents, teachers, other adults, and peers.
      Medication and behavioral treatment may improve different aspects of social
      impairment and may complement each other when used together. Much of the progress
      of treating social problems can be attributed to efforts to increase
      generalization across settings and durability of effects. A promising multimodal
      psychosocial approach is presented in detail.

PMID- 10944665
TI  - Presidential address: "What is the meaning of life?".

PMID- 10944664
TI  - Long-term prognosis in attention-deficit/hyperactivity disorder.
AB  - The authors have traced the developmental course of ADHD from childhood to
      adulthood, showing that it is a bumpy road for many. In early and middle
      adolescence, relative deficits are seen in academic and social functioning, ADHD
      symptoms remain problematic in two thirds to three quarters of these children,
      and antisocial behaviors, in some cases amounting to CD, are common. Many of
      these same difficulties persist into the late teenage years. Deficits continue to
      be observed in academic and social domains (compared with controls, probands
      exhibit lower grades, more courses failed, worse performance on standardized
      tests, have fewer friends, and are rated less adequate in psychosocial
      adjustment). About two fifths continue to experience ADHD symptoms to a
      clinically significant degree. One quarter to one third have a diagnosed
      antisocial disorder, and two thirds of these individuals are arrested. Also, drug
      abuse is observed in a significant minority of these youths. Importantly, the
      greatest risk factor for the development of antisocial behavior and substance
      abuse by the late teenage years is the maintenance of ADD symptoms. When
      evaluated in their mid-twenties, dysfunctions are apparent in these same areas.
      Compared with controls, probands complete less schooling, hold lower-ranking
      occupations, and continue to suffer from poor self-esteem and social skills
      deficits. In addition, significantly more probands than controls exhibit an
      antisocial personality and, perhaps, a substance use disorder in adulthood.
      Furthermore, many do not outgrow all facets of their childhood syndrome. These
      relative deficits, however, do not tell the whole story of the ADHD child's adult
      fate. Indeed, nearly all probands were gainfully employed. Furthermore, some had
      achieved a higher-level education (e.g., completed Master's degree, enrolled in
      medical school) and occupation (e.g., accountant, stock broker). In addition, a
      full two thirds of these children showed no evidence of any mental disorder in
      adulthood. In conclusion, although ADHD children, as a group, fare poorly
      compared with their non-ADHD counterparts, the childhood syndrome does not
      preclude attaining high educational and vocational goals, and most children no
      longer exhibit clinically significant emotional or behavioral problems once they
      reach their mid-twenties.

PMID- 10944666
TI  - Integrating technical innovations in everyday practice.

PMID- 10944667
TI  - Localizing the point: evolving principles of surgical navigation.

PMID- 10944668
TI  - Image-guided spinal navigation.

PMID- 10944669
TI  - The future of image-guided surgery.

PMID- 10944670
TI  - Epidemiology and cost of central nervous system injury.

PMID- 10944671
TI  - Pathophysiology of neural injury: therapeutic opportunities and challenges.

PMID- 10944672
TI  - The triage and acute management of severe head injury.

PMID- 10944673
TI  - Contemporary treatment paradigms in head injury.

PMID- 10944674
TI  - Contemporary treatment paradigms in spinal injury.

PMID- 10944675
TI  - Neurological injuries in infants and children: an overview of current management
      strategies.

PMID- 10944676
TI  - Evolving models of neurotrauma critical care: an analysis and call to action.

PMID- 10944677
TI  - Core curriculum in neurosurgical critical care.

PMID- 10944678
TI  - Outcomes science and neurotrauma: a national database.

PMID- 10944680
TI  - Organizing cerebrovascular care teams.

PMID- 10944679
TI  - Trauma: the neurosurgeon's domain.

PMID- 10944681
TI  - Diagnostic imaging for stroke.
AB  - With the advent of therapy for acute stroke via in intraarterial or intravenous
      pathway, early diagnosis with physician education is extremely important. A
      common theme in all studies is the continued stress on patient and physician
      education, rapid triage and diagnosis with the use of CT scanning, xenon blood
      flow or diffusion MRI, cerebral protection, and revascularization with either
      carotid surgery or percutaneous angioplasty for an offending lesion, if such is
      identified. Although the current studies are cautiously optimistic, prospective
      randomized trials are needed for the evaluation of intraarterial thrombolytics as
      well as percutaneous transluminal angioplasty. It is important that the
      neurosurgical community be identified as physicians who can diagnose and treat
      the patient with an acute stroke.

PMID- 10944682
TI  - Contemporary acute ischemic stroke therapy with intravenous recombinant tissue
      plasminogen activator.

PMID- 10944683
TI  - Honored guest presentation: management strategies for the treatment of
      intracranial arteriovenous malformations.

PMID- 10944684
TI  - Controversies in neurosurgery: microsurgery versus radiosurgery for arteriovenous
      malformations--the case for microsurgery.

PMID- 10944685
TI  - Therapeutic embolization of arteriovenous malformations: the case for and
      against.
AB  - The field of endovascular therapy has demonstrated stunning technical
      achievements in AVM embolization. Embolization has the potential to enhance the
      safety and efficacy of AVM treatment when applied in carefully considered cases.
      The utility of embolization, at the present time, is limited by the fact that the
      procedure may be associated with disabling or fatal complications, and because
      complete or near-complete AVM nidus occlusion can be achieved only in a minority
      of cases. Because of these factors, embolization should not be considered a
      "standard-of-care" for the management of all cerebral AVMs, and careful case
      selection for embolization, with well-defined treatment goals in mind, is
      essential. Finally, not all AVMs that can be embolized should be embolized.

PMID- 10944686
TI  - Treatment decisions in brain AVMs: the case for and against surgery.
AB  - Thus, it is clear that intracranial AVMs are a complex and heterogeneous
      condition, as are the patients they afflict. There is no true single strategy
      that is successful in even a majority of patients. The process of evaluation and
      management of AVM patients is a very strong argument for the creation of a
      "stroke center" in which a multidisciplinary team of cerebrovascular
      practitioners interacts collegially and effectively on a day-to-day basis for the
      management of the gamut of ischemic and hemorrhagic stroke problems.

PMID- 10944687
TI  - Honored guest presentation: therapeutic carotid occlusion.

PMID- 10944688
TI  - Therapeutic carotid occlusion: the case for prophylactic bypass.

PMID- 10944689
TI  - Selective use of extracranial-intracranial bypass as an adjunct to therapeutic
      internal carotid artery occlusion.

PMID- 10944690
TI  - Therapeutic carotid occlusion: current management paradigms.

PMID- 10944691
TI  - Therapeutic carotid occlusion: indications and potential complications.

PMID- 10944692
TI  - Honored guest presentation: therapeutic decisions in facial pain.
AB  - The authors recommend a multidisciplinary approach for the diagnosis and
      treatment of facial pain. With this approach, several experts can accurately
      diagnose various disorders of facial pain and offer appropriate treatment
      options, which should be tailored to the specific needs and general condition of
      the patient. For reporting and comparison, seek standardization of methods of
      analysis and outcomes criteria. Associate with a good secretary and nurse. For
      your patients' benefit, be an optimistic, caring, and attentive listener.

PMID- 10944693
TI  - Facial pain syndromes: practical considerations.

PMID- 10944695
TI  - Percutaneous treatment of trigeminal neuralgia: advances and problems.

PMID- 10944694
TI  - Contemporary medical management of facial pain.

PMID- 10944696
TI  - Neurovascular decompression: the procedure of choice?

PMID- 10944697
TI  - Trigeminal neuralgia: vascular compression theory.

PMID- 10944698
TI  - Endoscopic pituitary surgery.

PMID- 10944699
TI  - Endoscopic-assisted tumor and neurovascular procedures.

PMID- 10944700
TI  - Endoscopic spine surgery.

PMID- 10944701
TI  - Honored guest presentation: contemporary treatment of skull base meningiomas.

PMID- 10944702
TI  - Autoimmunity in liver diseases.

PMID- 10944704
TI  - Autoimmune polyglandular syndrome type 1.

PMID- 10944703
TI  - Immunopathogenesis of viral hepatitis.

PMID- 10944708
TI  - Relationship between striosomes and structural modules in the cat and human
      striatum.

PMID- 10944709
TI  - Plasmin enhances lymph flow.

PMID- 10944705
TI  - Primary sclerosing cholangitis.

PMID- 10944706
TI  - Xenobiotic-metabolizing enzymes as autoantigens in human autoimmune disorders. An
      update.

PMID- 10944710
TI  - Activation of serotonergic neurons by the metabolic precursor of serotonin: the
      effect of a tryptophan decarboxylase inhibitor.

PMID- 10944711
TI  - Cholinergic modification of monocomponent and binary model membranes prepared
      from brain phospholipids and glycosphingolipids.

PMID- 10944707
TI  - Primary biliary cirrhosis. Connecting molecular biology to clinical medicine.

PMID- 10944712
TI  - Study on the neurotropic activity of the products of Semax enzymatic degradation.

PMID- 10944713
TI  - Human blood serum and amniotic fluid contain an endogenous activator of beta
      adrenergic receptor synthesis (an indirect beta-adrenergic modulator).

PMID- 10944715
TI  - Selectivity of squirrel parastriate cortical neurons for speed and direction of
      moving stimuli.

PMID- 10944714
TI  - Cooperative interaction between motivational and emotional excitations: analysis
      of the spatial organization of EEG activity.

PMID- 10944716
TI  - Synaptic excitatory transmission under the conditions of chronically blocked
      ionotropic glutamate receptors.

PMID- 10944717
TI  - A synthetic dipeptide vilon (L-Lys-L-Glu) inhibits growth of spontaneous tumors
      and increases life span of mice.

PMID- 10944718
TI  - Proprioreceptors in Nephthys ciliata (Polychaeta, Errantia).

PMID- 10944719
TI  - Perception of visual-stimulus volume in affective disorders.

PMID- 10944720
TI  - Functional brain asymmetry and strategy for producing associations.

PMID- 10944721
TI  - Modifiers of cytoskeleton proteins and regulation of electron transport pathways
      of plant respiration.

PMID- 10944722
TI  - Regulation of population dynamics by pheromones in an opportunistic population of
      Daphnia magna (Cladocera) at a high ambient temperature.

PMID- 10944723
TI  - Exchange processes and distribution of microorganisms in the deep zone of Lake
      Baikal.

PMID- 10944724
TI  - The relationship between coat color variation and population dynamics in the
      water vole (Arvicola terrestris L.).

PMID- 10944725
TI  - The concept of aquatic biota as a labile and vulnerable component of the water
      self-purification system.

PMID- 10944726
TI  - Correlation between the structure of the rostellar apparatus and the shape of
      rostellar hooks in higher cestodes.

PMID- 10944727
TI  - The effect of Baliz-2 on the regeneration of rabbit ear skin after radiation
      induced and mechanical injury.

PMID- 10944728
TI  - Seasonal distribution and numbers of marine mammals in the Eastern Barents Sea.

PMID- 10944729
TI  - Effect of heterogeneity of the visual habitat on learning a food patch search
      task by the convict cichlid Cichlasoma nigrofasciatum (Pisces: Cichlidae).

PMID- 10944730
TI  - Variation in products of PCR using an arbitrary primer on a DNA template isolated
      from offspring of male mice exposed to low-dose radiation.

PMID- 10944731
TI  - Ecological subdivision of the Kola Bay (Barents Sea) pelagic zone using
      structural analysis of microplankton communities.

PMID- 10944732
TI  - RAPD markers of three breeds of honeybee Apis mellifera.

PMID- 10944733
TI  - Carbon emission by the southern tundra during cold seasons.

PMID- 10944734
TI  - Effect of ultrasound on arrow worms (Chaetognatha).

PMID- 10944735
TI  - On the presence of ossified maxilloturbinates of a new type in a Permian
      theriodont.

PMID- 10944736
TI  - Zygofabospora krassilnikovii, a wild European species, is an ancestor of the
      dairy yeasts Z. lactis.

PMID- 10944737
TI  - Localization of the secretory heat-shock protein gp280 in the cell envelope of
      thermotolerant yeast Hansenula polymorpha.

PMID- 10944738
TI  - DNA synthesis in heterokaryons obtained by fusion of hepatocytes from a
      regenerating mouse liver and NIH 3T3 fibroblasts.

PMID- 10944739
TI  - Promoter specificity of Escherichia coli rpoB403 mutant RNA polymerase.

PMID- 10944740
TI  - Monitoring blood glucose control in diabetes mellitus: a systematic review.

PMID- 10944742
TI  - An introduction to statistical methods for health technology assessment.

PMID- 10944741
TI  - Implantable contraceptives (subdermal implants and hormonally impregnated
      intrauterine systems) versus other forms of reversible contraceptives: two
      systematic reviews to assess relative effectiveness, acceptability, tolerability
      and cost-effectiveness.

PMID- 10944743
TI  - Disease-modifying drugs for multiple sclerosis: a rapid and systematic review.

PMID- 10944744
TI  - Cost and outcome implications of the organisation of vascular services.

PMID- 10944745
TI  - Quantitative dissection of transcriptional control system: N-dependent
      antitermination complex of phage lambda as regulatory paradigm.

PMID- 10944746
TI  - Problems and prospects in microcalorimetry of biological macromolecules.

PMID- 10944747
TI  - Probing stability of helical transmembrane proteins.
AB  - Sedimentation equilibrium in the analytical ultracentrifuge provides membrane
      biochemists with a tool to quantitatively probe thermodynamics of associating
      systems in detergent environments. As long as conditions of reversibility are
      met, the free energy of interaction can be measured in varied hydrophobic
      environments, pH values, ionic strengths, and temperatures. Although the absolute
      value of the interaction free energy of membrane protein subunits will no doubt
      depend on the hydrophobic environment, experiments in any one environment will
      allow subunit associations to be placed on a relative scale of interaction. The
      temperature dependence of the free energy change may provide more thorough
      information about the thermodynamics of helix-helix association in micelles.

PMID- 10944748
TI  - Energetics of vinca alkaloid interactions with tubulin.

PMID- 10944749
TI  - Kinetics and thermodynamics of conformational equilibria in native proteins by
      hydrogen exchange.

PMID- 10944750
TI  - Mathematical modeling of cooperative interactions in hemoglobin.

PMID- 10944751
TI  - Deriving complex ligand-binding formulas.

PMID- 10944752
TI  - Calculation of entropy changes in biological processes: folding, binding, and
      oligomerization.
AB  - Changes in configurational entropy represent one of the major contributions to
      the thermodynamics of folding, binding, and oligomerization. Methods have been
      developed to estimate changes in the entropy of the backbone and side chains, and
      for the loss of translational entropy. These methods have been used in
      combination with empirical methods that provide estimates of the changes in
      entropy of solvation as well as estimates of the changes of enthalpy. The results
      of such calculations are in excellent agreement with experimentally observed
      values.

PMID- 10944753
TI  - Evaluating energetics of erythropoietin ligand binding to homodimerized receptor
      extracellular domains.

PMID- 10944754
TI  - Measurement of protein interaction bioenergetics: application to structural
      variants of anti-sCD4 antibody.
AB  - This chapter has described a bioenergetic analysis of the interaction of sCD4
      with an IgG1 and two IgG4 derivatives of an anti-sCD4 MAb. The MAbs have
      identical VH and VL domains but differ markedly in their CH and CL domains,
      raising the question of whether their antigen-binding chemistries are altered. We
      find the sCD4-binding kinetics and thermodynamics of the MAbs are
      indistinguishable, which indicates rigorously that the molecular details of the
      binding interactions are the same. We also showed the importance of using
      multiple biophysical methods to define the binding model before the bioenergetics
      can be appropriately interpreted. Analysis of the binding thermodynamics and
      kinetics suggests conformational changes that might be coupled to sCD4 binding by
      these MAbs are small or absent.

PMID- 10944755
TI  - Analysis of interaction of regulatory protein TyrR with DNA.

PMID- 10944756
TI  - Proteolytic footprinting titrations for estimating ligand-binding constants and
      detecting pathways of conformational switching of calmodulin.
AB  - To dissect the chemical basis for interactions controlling regulatory properties
      of macromolecular assemblies, it is essential to explore experimentally the
      linkage between ligand binding, conformational change, and subunit assembly.
      There are many advantages to using techniques that will probe the occupancy of
      individual binding sites or monitor conformational responses of individual
      residues, as described here. Proteolytic footprinting titrations may be used to
      infer binding free energies for ligands interacting with multiple sites or
      domains and to detect otherwise unrecognized "silent" interdomain interactions.
      Microgram quantities of pure protein are required, which is low relative to the
      hundreds of milligrams needed for comparable discontinuous equilibirum titrations
      monitored by NMR. By running comparative studies with several proteases, it is
      easy to determine whether resulting titration curves are consistent, independent
      of the protease used and therefore representative of the structural response of
      the protein to ligand binding or other differences in solution conditions (pH,
      salt, temperature). The results from multiple techniques (e.g., NMR,
      fluorescence, and footprinting) applied to aliquots from the same discontinuous
      titration may be compared easily to test for consistency. Classic methods for
      determining thermodynamic and kinetic properties of calcium binding to calmodulin
      include filter binding and equilibrium or flow dialysis (employing the isotope
      45Ca), spectroscopic studies of stopped-flow fluorescence, calorimetry, and
      direct ion titrations. A cautionary note is that many different sets of
      microscopic data would be consistent with a single set of macroscopic constants
      determined by classic methods. This was well illustrated in Fig. 9. Thus, while
      it is important to compare results with those obtained by classic binding
      methods, they are, by definition, incapable of resolving the microscopic
      constants of interest. Thus, there is only one "direction" for comparison.
      Quantitative proteolytic footprinting titrations applied to studying calmodulin
      provided the first direct quantitative estimate of negative interactions between
      domains. Although studies of site-knockout mutants had suggested interactions
      between domains, this approach gave the first evidence for the pathway of
      anticooperative interactions between domains by showing that helix B responds
      structurally to calcium binding to sites III and IV in the C-domain. Despite two
      decades of study of calmodulin and the application of limited proteolysis studies
      to the apo and fully saturated forms, this finding emerged only when titration
      studies were undertaken as described. This highlights the general observation
      that while the behavior of the intermediate states in a cooperative switch are
      the key elements of the transition mechanism, they are the most difficult to
      observe. The unexpected finding that the isolated domains are nearly equivalent
      in their calcium-binding properties (Fig. 23 B) leaves us with many of the
      questions we had at the start: How does the sum of two nearly equivalent domains
      result in a molecule that switches sequentially rather than simultaneously? But
      it underscores why it is not yet possible to understand similar proteins by
      sequence gazing alone.

PMID- 10944757
TI  - Analysis of reversibly interacting macromolecular systems by time derivative
      sedimentation velocity.

PMID- 10944758
TI  - Kinetic, equilibrium, and thermodynamic analysis of macromolecular interactions
      with BIACORE.

PMID- 10944759
TI  - Structure-function relationships in two-component phospholipid bilayers: Monte
      Carlo simulation approach using a two-state model.

PMID- 10944760
TI  - Parsing free energies of drug-DNA interactions.

PMID- 10944761
TI  - Direct measurement of sodium ion release from DNA on binding of cationic ligands.

PMID- 10944762
TI  - Enthalpy-entropy compensations in nucleic acids: contribution of electrostriction
      and structural hydration.

PMID- 10944763
TI  - Time-resolved fluorescence methods for analysis of DNA-protein interactions.

PMID- 10944764
TI  - Use of fluorescence spectroscopy as thermodynamics tool.

PMID- 10944765
TI  - Microsecond dynamics of biological macromolecules.

PMID- 10944767
TI  - [Preoperative photodynamic therapy for lung cancer].
AB  - In Japan, photodynamic therapy (PDT) for locally superficial hilar lung cancer is
      common and its indications have already been determined. In order to improve the
      survival rate for lung cancer patients, it is necessary to increase the number of
      operable cases and preserve pulmonary function, and it thus would be beneficial
      to reduce the extent of resection. In our institution, preoperative PDT has been
      employed as one option to reduce the extent of resection. Nineteen patients who
      were initially planned to undergo pneumonectomy underwent successful lobectomy.
      For multiple primary lung cancer lesions, combined use of PDT was carried out in
      29 cases. For early-stage lung cancer, PDT was performed and for advanced lesions
      surgery was selected. These new options may contribute to the management of
      advanced lung cancer.

PMID- 10944766
TI  - [Extended segmentectomy for small lung tumors].
AB  - To identify the benefits of limited surgery on small-sized lung tumors, the
      following subjects are discussed: 1) an updated report from a prospective group
      study (January 1992-December 1994) for extended segmentectomy for small lung
      tumors (n = 55); 2) a histopathological study of resected adenocarcinoma
      specimens less than 2 cm in size (n = 94), proposed by Noguchi; and 3) lung
      function after limited surgery and the quality of video-assisted thoracoscopic
      surgery. RESULTS: 1) Among 10 deaths, 4 patients died of their disease including
      one with local recurrence. The survival rate at 5 years was 91%, not including 6
      unrelated deaths. 2) Of 94 patients, twelve with localized bronchioalveolar
      tumors (type A and B), and 23 of 57 patients with active fibroblastic
      proliferation (type C), underwent extended segmentectomy. Those 35 patients are
      all free of disease. The remaining 59 patients had a 70% 5-year survival rate. 3)
      Forced vital capacity was maintained at 92% of the preoperative level, which was
      much better than 81% for patients undergoing lobectomy. Card-sized thoracotomy
      using a thoracoscope was carried out in 92 patients, including 21 patients who
      underwent segmentectomy, in a series of 175 consecutive lung cancer operations.
      This approach resulted in less bleeding, the same operating time, and better
      preservation of vital capacity. CONCLUSIONS: Extended segmentectomy for small
      lung tumors did not affect the prognosis, and was associated with a better
      quality of life postoperatively.

PMID- 10944768
TI  - [Limited operation of lung cancer: the role of video-assisted thoracic surgery
      for lung cancer].
AB  - Lobectomy with systemic nodal dissection is recognized as a standard operation
      for lung cancer. Partial resection and segmental resection are classified as
      limited resections for lung cancer to preserve pulmonary function. Minor
      complications occur more frequently with limited resection than with lobectomy.
      Partial resection of the lung and simple lobectomy can be performed as video
      assisted thoracic surgery (VATS). Systemic hilar and mediastinal lymph node
      dissection is not yet standardized using VATS. On the other hand, VATS preserves
      chest wall muscles. The difference between standard thoracotomy and VATS is a
      difference of approach to the thoracic cavity. It is most important for lung
      cancer surgery to be performed in the thoracic cavity with the minimum burden on
      patients.

PMID- 10944769
TI  - [Surgical treatment for severe pulmonary emphysema].
AB  - Volume reduction surgery (VRS) has been adopted for patients with severe
      pulmonary emphysema who complain of continuous exertional dyspnea in daily life.
      VRS comprises two types of surgical procedure: resection of the peripheral lung
      by median sternotomy; and the thoracoscopic approach. The latter is considered to
      be less invasive and better tolerated by patients in poor physical condition,
      while the former has the disadvantage of heavier bleeding during surgery.
      However, postoperative air leakage tends to be much less with median sternotomy
      compared to thoracoscopic VRS.

PMID- 10944770
TI  - [Tracheal reconstruction].
AB  - Progress in anesthesia, surgical techniques, and understanding of the
      pathophysiology of the trachea has made tracheal reconstruction a safe operative
      procedure. As of December 1999, 109 patients had undergone tracheal
      reconstruction at the author's institution. Diseases included: tumorous lesions
      in 83, consisting of 13 primary tracheal tumors and 70 carcinomatous invasions
      originating from adjacent organs such as thyroid cancer; and 26 benign stenotic
      lesions such as postintubation stenosis in 15, posttraumatic stenosis in 9, and
      congenital and tuberculous stenosis in one case each. Among the 109 patients,
      resection of the trachea and end-to-end anastomosis were performed in 105
      patients and partial resection of the trachea with direct closure was done in 4
      patients. Complications at anastomosis were seen in 5 patients, with stenosis at
      anastomosis in 2, suture failure in 2, and malacia in one. The most frequent
      lesion seen at our institution was thyroid carcinoma invading the trachea in 64
      patients. The number of tracheal rings resected ranged from 1 to 11, with an
      average of 6. Complete resection was done in 34 of these 64 patients, and their 5
      and 10-year survival rates were 79.4% and 75.6%. In 30 patients in whom
      resection was incomplete the 5- and 10-year survival rates were 52.8% and 35.5%,
      respectively. Tracheal reconstruction for another tumorous and non tumorous
      origins improved QOL of patients suffering from cough, sputum, hemosputum and
      dyspnea, and it was even life saving.

PMID- 10944771
TI  - [Tracheobronchoplasty for lung cancer: operative indications by limited
      category].
AB  - Three limited categories of tracheobronchoplasty are applicable in lung cancer
      patients. A1 is for patients who would otherwise be inoperable due to the lack of
      cardiopulmonary reserve. R1 is for early-stage cancer localized to the hilar
      bronchus and which aims to preserve lung function by active limited category. R3
      tracheo-bronchoplasty preserves respiratory function in noncurative cases. The
      percentage of patients undergoing A1, R1, and R3 tracheo-bronchoplasty were
      14.2%, 16.8% and 4.2%, respectively (35.2% of total patients undergoing
      bronchoplasty). Of the total patients, 18.9% underwent carinoplasty, and of these
      only 4 (2.6%) were eligible for the 3 categories of tracheo-bronchoplasty. Of
      lung cancer patients who underwent bronchoplasty, A1 was performed in 12.6%, R1
      in 16/3%, and R3 in 3.7% (32.6% of the total). The use of bronchoplasty increased
      from 7.8% to 21.9% of lung cancer surgery after the introduction of dose
      intensive induction chemotherapy (DIIC), mainly due to the increase in the use of
      interlobar techniques (20.5% of the total) in the smaller bronchial lesions
      present after DIIC. The 5-year survival rates of patients undergoing A1, R1, and
      R3 tracheo-bronchoplasty were 59.6%, 64.9%, and 0%, respectively. No anastomotic
      recurrence was seen in the 32 patients who underwent R1. Based on these results,
      tracheo-bronchoplasty increases survival in patients who receive the A1 category
      and preserves lobar function in those who receive R1 and R3.

PMID- 10944772
TI  - Recent perspectives in the design of antiasthmatic agents.
AB  - Asthma is a common respiratory disorder. It can no longer be viewed as a
      reversible airway obstruction but should instead be considered primarily as an
      inflammatory illness that has bronchial hyperreactivity and bronchospasm as its
      result. There are several potential benefits as well as limitations of the
      currently available antiasthmatic agents such as anticholinergics, beta 2
      selective agonists, methylxanthines, corticosteroids, or mast cell stabilizers.
      Recent trends in the design of new antiasthmatic agents include isozyme selective
      phosphodiesterase inhibitors, inhibitors of the biosynthesis of interleukin-4 and
      IL-4 antagonists, lipoxygenase and leukotriene inhibitors, thromboxane A2
      receptor antagonists, potassium channel openers and monoclonal antibodies.

PMID- 10944773
TI  - Antidermatophytic action of new 1-naphthylmethyl and benzo[b]thiophen-7-ylmethyl
      hydrazones related to inhibitors of squalene epoxidase.
AB  - Two series of hydrazonic compounds related to main classes of inhibitors of
      fungal squalene epoxidase (SE) were designed and prepared on the hypothesis of a
      pharmacophoric model. The antifungal activity of the new compounds was evaluated
      in vitro against dermatophytes, moulds and yeasts. Antidermatophytic activity
      resulted for several hydrazones, particularly for those containing a tett
      butylacetylenic group, supporting the hypothesis that the introduction of a
      hydrazonic function in the model could retain the antimycotic activity.

PMID- 10944774
TI  - Ureylene anticonvulsants and related compounds.
AB  - The results from a previous study led to the postulate that a number of aryl
      semicarbazones displaying anticonvulsant activity in the maximal electroshock
      (MES) screen interacted at both a hydrophobic and a hydrogen bonding areas on a
      specific binding site. These two parts of the binding site may be referred to as
      areas A and B, respectively. In order to circumvent the possible problems of the
      carbimino group in semicarbazones, such as toxicity and acid lability, some
      related ureylenes were considered. Initial evidence suggested that a second
      lipophilic group in the molecule was advantageous; this group may interact at
      area C on the proposed binding site. Most of the compounds prepared with a view
      to interacting at areas A, B and C showed protection in mice against MES induced
      seizures. Of particular interest were the compounds 1d, j which contained an
      alpha-methylbenzyl group attached to the N1 atom of the ureylenes which afforded
      good protection in the MES screen. The areas A and C at which lipophilic moieties
      were considered to interact were capable of accommodating groups of different
      sizes as measured by their solvent accessible surface areas. A number of
      compounds were active when given orally to rats and devoid of neurotoxicity at
      the doses utilized. Several compounds including 1d, f, j, 2d are useful
      prototypic molecules for subsequent development of further novel anticonvulsants.

PMID- 10944776
TI  - Synthesis of new [1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidinone derivatives
      with antiinflammatory activity.
AB  - New thiadiazolothienopyrimidinones were synthesized in continuation of efforts to
      prepare thienopyrimidine derivatives with analgesic and antiinflammatory
      activities. In this study, the effect of various substituents in the thiophene
      ring on the pharmacological activity of the compounds was investigated.

PMID- 10944775
TI  - Antilipidemic agents, Part. IV: Synthesis and antilipidemic testing of some
      heterocyclic derivatives of hexadecyl and cyclohexyl hemisuccinate esters.
AB  - Two main classes of novel esters containing a hexadecyl or cyclohexyl group and
      various heterocyclic rings, like quinazolines, triazoles, thiadiazoles and
      pyrazoles have been synthesized. The first class involves the synthesis of the
      hexadecyl ester derivatives; namely 3-substituted-2
      (hexadecyloxycarbonylpropionylthio)-4(3H)-quinazol inones 4a-c; 4-substituted-3
      (4-pyridyl)-5-(hexadecyloxycarbonylpropionylthio)- 4H- 1,2,4-triazoles 6a-c; 5
      substituted-2-(hexadecyloxycarbonylpropionylamino)-1,3,4-thiadia zoles 8a-c, 4-[4
      (hexadecyloxycarbonyl)phenyl]azo-5-hydroxy-3-methyl-1-phen ylpyrazole 16; and 1
      [4-(hexadecyloxycarbonyl) phenyl]-3-methyl-2-pyrazolin-5-one 19. The second class
      comprises the synthesis of the cyclohexyl ester derivatives; namely 3-substituted
      2-(cyclohexyloxycarbonylpropionylthio)-4(3H)-quinazo linones 11a, b, 4
      substituted-3-(4-pyridyl)-5-(cyclohexyloxycarbonylpropionylthio) -4 H-1,2,4
      triazoles 12a, b and 5-isopropylthio-2-(cyclohexyloxycarbonylpropionylamino)-1,3,
      4-thiadiazole 13. The antihypercholesterolemic as well as antihyperlipidemic
      activities of representative compounds have been studied. All the compounds
      tested resulted in a decrease in the lipid indices (cholesterol, LDL-cholesterol,
      HDL-cholesterol and serum triglycerides levels) studied in mice. Compounds 4b,
      11a and 12a showed the highest antihyperlipidemic activity; their activities were
      almost equal to that of beta-sitosterol which was used as a standard.

PMID- 10944777
TI  - Characterization of dimethyldiacyloxysilanes by differential scanning
      calorimetry, Raman scattering and X-ray diffraction.
AB  - The phase behaviour of diacyloxydimethylsilanes (DMS Cn; n = 10, 12, 14, 16, 18,
      20, 22) was investigated by differential scanning calorimetry, X-ray diffraction
      and Raman spectroscopy. All DMS Cn melt from a crystalline phase to an isotropic
      liquid with a single sharp transition. On cooling, the homologous DMS C16 up to
      DMS C22 show a characteristic monotropic phase (L beta'H). In contrast to the
      calorimetrical investigations, it was not possible to analyse the monotropic
      phase of DMS C16 by X-ray diffraction. This behaviour is due to a two-phase
      region (gel phase--crystalline phase). The Raman spectra of all DMS are very
      similar. Only in the low frequency range we find different bands of the
      longitudinal acoustic modes. The Raman measurements demonstrate undoubtedly that
      in the solid state the alkyl chains are in all-trans conformation. The factor
      group splitting of the CH2 scissoring Raman mode show that the DMS Cn are
      arranged in a subcell packing with two molecules per unit cell. The highly
      ordered all-trans structure of the alkyl chains is present up to the melting
      transition. On melting there are changes in different regions of the Raman
      spectra: C-H stretching, CH2 scissoring mode, C-C skeletal stretching, CH3
      rocking and longitudinal acoustic modes. On cooling DMS C18 and DMS C20 from the
      melt to the crystalline state, the gel phase is also proved by Raman scattering.
      Based on the results of the Raman and X-ray data the gel phase is characterized
      by a hexagonal subcell packing and by an ordered structure of the alkyl chain
      residues.

PMID- 10944778
TI  - Stability of polymorphic forms of ranitidine hydrochloride.
AB  - Ranitidine-HCl can exist in two different polymorphic forms: form I (m.p. 134-140
      degrees C) and form II (m.p. 140-144 degrees C). In the present study the
      stability of form I of ranitidine-HCl to a selection of powder pretreatments, to
      reflect conditions which might occur in manufacturing procedures, and also to a
      limited range of storage conditions was investigated. The original samples of
      form I and form II used were characterised by X-ray powder diffraction (XRPD),
      hot stage microscopy (HSM) and differential scanning calorimetry (DSC). A
      quantitative XRPD method for determining the fraction of form II in the presence
      of form I was used. XRPD data were analysed using regression techniques and
      artificial neural networks (ANN). The quantitative XRPD technique was then used
      to monitor the relative proportion of form II in each treated sample.
      Pretreatments of form I included (i) mixing with form II or with common
      excipients (ii) compression and grinding (iii) contact with solvents (followed by
      drying) before storage. Storage conditions involved three temperatures (20
      degrees C, 30 degrees C, 42 degrees C) and three relative humidities (45% RH; 55%
      RH; 75% RH). Samples were stored for a period of 6 months. A limited factorial
      design was used. No increase in the form II:form I ratio was observed in the
      following pretreatment processes: introduction of form II nuclei into form I;
      introduction of excipients to form I; compression of form I powder at 5 and 15
      tons; normal mixing and grinding processes; addition of isopropanol (IPA) or
      water/IPA mix followed by drying. In the pretreatment process where water was
      added to form I powder (with most or all of the powder dissolving), drying of the
      liquefied mass led to a mix of form I and form II. On storage at room temperature
      (20-30 degrees C), low relative humidity (45-55% RH), and in an air-tight
      container there was no increase in the form II:form I ratio. Storage of form
      I/form II mixes, particularly at high humidity, resulted in a preferential loss
      of form II (compared to form I). Loss was greater at 30 degrees C/75% RH than at
      20 degrees C/75% RH. Form II was also preferentially lost under low humidity
      conditions created by a saturated solution of potassium carbonate (45% RH) at the
      elevated temperature of 42 degrees C. This environment was shown to be acidic.

PMID- 10944779
TI  - In vitro and in vivo evaluation of an amylobarbitone/hydroxypropyl-beta
      cyclodextrin complex prepared by a freeze-drying method.
AB  - The complex formation of amylobarbitone (AMB) with 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) was investigated in aqueous solution and in the solid
      state. The apparent stability constant for complex formation (Kc) calculated by
      phase solubility and spectral shift methods was 524 M-1 and 568 M-1,
      respectively. The stoichiometric molar ratio of the complex was estimated to be
      1:1 and the solubility of AMB in water was increased about 3 fold. The solid
      dispersion system of AMB/HP-beta-CD in 1:1 molar ratio was prepared by a freeze
      drying method. Differential scanning calorimetry (DSC), x-ray diffractometry,
      (IR) and 1H NMR spectroscopy were used to confirm that inclusion between the drug
      and HP-beta-CD occurred. The dissolution behavior of the drug as a physical
      mixture as well as the prepared complex, showed enhanced drug dissolution
      properties of the prepared complex compared to the physical mixture or the drug
      alone. The dissolution rate appeared in the first 2 min, 25 times greater for the
      complex than for the drug alone. Furthermore, in-vivo study revealed that the
      duration and hypnotic activity of AMB after its oral administration to mice were
      improved by inclusion.

PMID- 10944780
TI  - Effect of hydroxypropyl-beta-cyclodextrin on hydrocortisone dissolution from
      films intended for ocular drug delivery.
AB  - The formation of an inclusion complex between hydrocortisone and hydroxypropyl
      beta-cyclodextrin can affect the in vitro transfer rate of hydrocortisone from
      the aqueous to the organic phase. The observed first order transfer rate
      constants showed that the complexation of hydrocortisone with hydroxypropyl-beta
      cyclodextrin decreased significantly the transport of the drug depending on the
      partition coefficient of the drug, and the relative magnitude of the stability
      constant of the inclusion complex. To optimize the ocular drug delivery, high
      molecular weight cellulosis and PVA polymeric films were prepared. No unified
      mathematical model can predict the release profile of drug and complex from
      films. The drug and complex-polymer interactions in each system could be
      responsible for the solubility of the drug, and different release behaviours of
      hydrocortisone and cyclodextrin inclusion complex from the films prepared.

PMID- 10944781
TI  - [Granule formation mechanisms in fluid-bed melt granulation and their effects on
      tablet properties].
AB  - Melt granulations of lactose and PEG 4000 were made with a fluid-bed granulator
      and for comparison in a high-speed mixer with scraper. Two different mechanisms
      of granule formation occurred, coalescence and layering. The agglomeration
      kinetics of layering was modeled. The granulations were compressed on an
      instrumented press and examined for uniformity of mass, hardness and
      disintegration time. Remarkable differences in tablet properties were found
      between the mechanisms of granule formation.

PMID- 10944782
TI  - Polymeric colloidal systems containing ethionamide: preparation and physico
      chemical characterization.
AB  - The association of ethionamide with different colloidal systems was evaluated.
      Nanocapsules (NC), nanospheres (NS), and nanoemulsions (NE) were prepared by
      interfacial deposition and spontaneous emulsification techniques. Ethionamide was
      incorporated before (B) and after (A) preparation of nanoparticles. Ethionamide
      was assayed by HPLC, the particle size was determined using a Nanosizer, and the
      zeta potential using a Zetasizer 4. Free ethionamide was determined using a
      combined ultrafiltration-centrifugation technique. The drug release was
      determined by direct dilution of the nanoparticle dispersion in phosphate-buffer
      pH 7. All preparations retained acceptable particle size distribution (+/- 300
      nm), except the NE. The zeta potential of all formulations was between -36.6 mV
      and -46.1 mV. Percentages of ethionamide associated were: NC (B: 62.4%, A:
      56.2%), NS (B: 53.0%, A: 43.2%), and NE (B: 38.5%). After 45 days, the percentage
      of drug association with NC increased (B: 66.8%, A: 60.6%). The release profiles
      demonstrated that associated ethionamide was more readily released from the NC
      and NS prepared by procedure A rather than B. The ethionamide amount not released
      (B) was greater in NS than NC. The drug is mainly adsorbed onto the surface of
      nanoparticles. However, approximately 10% of ethionamide is encapsulated into NC
      and 20% entrapped into NS, respectively.

PMID- 10944783
TI  - The structure of the ring-opened N beta-propyl-ajmaline (Neo-Gilurytmal) at
      physiological pH is obviously responsible for its better absorption and
      bioavailability when compared with ajmaline (Gilurytmal).
AB  - Prajmaline, the semisynthetic propyl derivative of ajmaline, shows a much better
      bioavailability when compared with the Rauvolfia alkaloid ajmaline. Early NMR and
      IR-studies, fluorescence spectroscopic investigations and extraction experiments
      combined with ion-pair chromatography proved the thesis of a tautomeric
      equilibrium between an aldehyde-amine and a quaternary carbinol-ammonium
      component. The aim of this study was to confirm this thesis by HPLC-separation
      and by structure-determination of both tautomeric compounds.

PMID- 10944784
TI  - Treatment of adjuvant arthritis in mice with yeast superoxide dismutase.
AB  - Yeast Cu/Zn superoxide dismutase (SODy) was used for treatment of adjuvant
      induced arthritis in mice. SODy was applied intraperitoneally (i.p.) in doses of
      10 mg/kg (30,000 U/kg) and 30 mg/kg (90,000 U/kg) one or three times daily on
      consecutive days. It was very effective in reducing the paw swelling whether
      administered before or immediately after induction or when the treatment began at
      the onset of inflammation or at the peak of the arthritic process. The effect of
      yeast SOD was compared to that of commercial SOD from bovine erythrocytes (SODb),
      as well as with indomethacin treatment. Histological data confirmed the
      antiinflammatory effect of yeast SOD. The schedules and doses tested did not
      elicit anti-SOD antibodies in serum.

PMID- 10944785
TI  - A new lanostane triterpenic ether from Adiantum venustum.
AB  - A new lanostane triterpenic ether, lanost-20(22)-en-3,19-ether, named
      adiantulanostene ether was isolated from Adiantum venustum. Its structure was
      elucidated on the basis of full spectral data analyses and chemical means.

PMID- 10944786
TI  - Study of local anaesthetics. Part 152: Some piperidinomethyl esters of alkoxy
      substituted phenylcarbamic acids.

PMID- 10944787
TI  - HPTLC densitometric determination of ruscogenins in dry extract of Ruscus
      aculeatus L.

PMID- 10944788
TI  - Plasma protein binding properties of dimeric 4-aryl-1,4-dihydropyridines as novel
      non peptidic HIV-1 protease inhibitors.

PMID- 10944789
TI  - Determination of atenolol/chlortalidone during dissolution of tablets with UV
      multicomponent analysis.

PMID- 10944790
TI  - Solubilisation of poorly water soluble non-steroidal anti-inflammatory drugs at
      low pH with N-methylglucamine.

PMID- 10944791
TI  - The changes of capacitance relaxation of bilayer lipid membranes induced by
      chlorpromazine.

PMID- 10944792
TI  - In vitro study of antiyersinious effects of Oxadin.

PMID- 10944793
TI  - A new steroidal saponin from the bulbs of Lilium candidum L.

PMID- 10944794
TI  - Sesquiterpenoids from Scorzonera hispanica L.

PMID- 10944795
TI  - Introduction to immunostimulatory DNA sequences.

PMID- 10944796
TI  - The discovery of immunostimulatory DNA sequence.

PMID- 10944797
TI  - Mechanisms of immune stimulation by bacterial DNA.

PMID- 10944799
TI  - Activation of skin dendritic cells by immunostimulatory DNA.

PMID- 10944798
TI  - Activation of NK cell (human and mouse) by immunostimulatory DNA sequence.

PMID- 10944800
TI  - Rescue of B cells from apoptosis by immune stimulatory CpG DNA.

PMID- 10944801
TI  - The response of human B lymphocytes to oligodeoxynucleotides.

PMID- 10944802
TI  - Multiple effects of immunostimulatory DNA on T cells and the role of type I
      interferons.
AB  - In addition to stimulating antigen-specific immune responses, infectious agents
      cause nonspecific activation of the innate immune system, notably up-regulation
      of costimulatory/adhesion molecules on APCs and cytokine production. In recent
      years it has become apparent that stimulation of the immune system by
      microorganisms is a property of a number of different cellular components,
      including DNA. As discussed earlier and elsewhere in this volume, the DNA of
      infectious agents--and indeed of all non-vertebrates tested--differs from
      mammalian DNA in being enriched for unmethylated CpG motifs. With appropriate
      flanking sequences, CpG DNA and synthetic CpG ODNs cause strong activation of
      APCs and other cells. In this article we have focussed on the capacity of CpG
      DNA/ODNs to alter T cell function. Whether these compounds act directly on T
      cells or function indirectly by activating other cells, especially APCs, is
      controversial [7, 8, 13, 14]. In contrast to other workers [8], we have yet to
      find definitive evidence that CpG DNA/ODNs can provide a co-stimulatory signal
      for purified T cells subjected to TCR ligation ([14] and unpublished data of
      authors). For this reason we lean to the notion that CpG DNA/ODNs modulate T cell
      function by inducing activation of APC rather than by acting directly on T cells.
      When injected in vivo in the absence of specific antigen, CpG DNA/ODNs have two
      striking effects on T cells, namely (1) induction of overt activation
      (proliferation) of memory-phenotype CD8+ cells, and (2) partial activation of all
      T cells, including naive-phenotype T cells. Both actions of CpG DNA/ODNs are
      heavily dependent on the production of IFN-I by APC. For memory-phenotype
      (CD44hi) CD8+ cells, neither CpG DNA nor IFN-I can cause proliferation of
      purified APC-depleted T cells in vitro. Hence, under in vivo conditions, CpG DNA
      induced proliferation of CD44hi CD8+ cells is probably mediated through the
      production of a secondary cytokine, i.e., by a cytokine that is directly
      stimulatory for CD44hi CD8+ cells. Based on the available evidence, it is highly
      likely that the effector cytokine is IL-15. With this assumption, our current
      model is that proliferation of CD44hi CD8+ cells induced by injection of CpG
      DNA/ODNs reflects production of IFN-I which, in turn, leads to synthesis of IL
      15. Which particular cell types produce these two cytokines is unclear, although
      APCs are probably of prime importance. In addition to inducing proliferation of
      memory-phenotype CD8+ cells via IL-15, the IFN-I induced by CpG DNA/ODNs can also
      induce partial activation of naive T cells. This form of activation leads to up
      regulation of CD69 and other molecules but does not cause entry into cell cycle.
      It is of interest that the partial activation of naive T cells induced by IFN-I
      is associated with decreased T proliferative responses. Thus, proliferation of
      purified naive T cells elicited by combined TCR/CD28 ligation in vitro is greatly
      reduced by addition of IFN-I. This inhibitory effect of IFN-I does not influence
      cytokine production and probably reflects production of cell cycle inhibitors.
      Surprisingly, except at high doses, IFN-I fails to exert an anti-proliferative
      effect when T proliferative responses are driven by viable APCs. Indeed, in this
      situation, IFN-I enhances antigen-specific T proliferative responses, both in
      vivo and in vitro. This adjuvant effect of IFN-I is presumably a reflection of
      APC activation, but direct evidence on this issue is still lacking. In this
      article we have emphasized that contact with CpG DNA/ODNs has multiple effects on
      T cell function in vivo. Many of these effects seem to be related to the
      production of certain cytokines by APCs, notably IFN-I and IL-15. It should be
      stressed, however, that CpG DNA/ODNs probably lead to the production of many
      other cytokines. Hence, our current models of how CpG DNA/ODNs influence T cell
      function are undoubtedly oversimplified.

PMID- 10944803
TI  - Pre-priming: a novel approach to DNA-based vaccination and immunomodulation.

PMID- 10944804
TI  - Signal transduction induced by immunostimulatory CpG DNA.
AB  - The immune recognition of unmethylated CpG motifs appears to be an example of the
      ability of the immune system to detect molecular patterns which are
      characteristic of microbes, but are not present in vertebrates. This detection is
      accomplished by the means of pattern recognition receptors (PRR). Unlike some
      other examples of PRR, immune recognition of CpG DNA appears to require cell
      uptake and to be accomplished through an intracellular PRR system. This then
      results in the activation of mitogen-activated protein kinases, culminating in
      the phosphorylation of transcription factors and the activation of transcription
      and translation. The rapid activation of these pathways by CpG DNA leads to the
      induction of protective immune responses.

PMID- 10944805
TI  - Immunostimulatory DNA sequences and cancer therapy.

PMID- 10944807
TI  - The role of CpG in DNA vaccines.
AB  - One of the most exciting developments in the field of vaccine research in recent
      years has been DNA vaccines, with which immune responses are induced subsequent
      to the in vivo expression of antigen from directly introduced plasmid DNA. Strong
      immune responses have been demonstrated in a number of animal models against many
      viral, bacterial and parasitic pathogens, and several human clinical trials have
      been undertaken. The strong and long-lasting antigen-specific humoral
      (antibodies) and cell-mediated (T help, other cytokine functions and cytotoxic T
      cells) immune responses induced by DNA vaccines appear to be due to the sustained
      in vivo expression of antigen, efficient antigen presentation and the presence of
      stimulatory CpG motifs. These features are desirable for the development of
      prophylactic vaccines against numerous infectious agents. Furthermore, the strong
      cellular responses are also very desirable for the development of therapeutic DNA
      vaccines to treat chronic viral infections or cancer. Efforts are now focusing on
      understanding the mechanisms for the induction of these immune responses, which
      in turn should aid in the optimization of DNA vaccines. This review will focus on
      the role of CpG motifs in DNA vaccines.

PMID- 10944806
TI  - Modulation of asthmatic response by immunostimulatory DNA sequences.

PMID- 10944808
TI  - Mucosal adjuvanticity of immunostimulatory DNA sequences.

PMID- 10944809
TI  - Immunostimulatory DNA sequences help to eradicate intracellular pathogens.

PMID- 10944810
TI  - The antigenic properties of bacterial DNA in normal and aberrant immunity.

PMID- 10944811
TI  - The role of immunostimulatory CpG-DNA in septic shock.

PMID- 10944813
TI  - [Transplantation of hands in Innsbruck].

PMID- 10944812
TI  - Activation of the innate immune system by CpG oligodeoxynucleotides:
      immunoprotective activity and safety.

PMID- 10944814
TI  - Pneumonia in the elderly--what makes the difference?
AB  - Pneumonia has a particularly high incidence in the elderly, the cardinal risk
      factors being comorbidity and malnutrition. The independent bearing of age on the
      aetiology of pneumonia is a matter of controversy and is probably limited.
      Streptococcus pneumoniae is uniformly the most frequent pathogen. Elderly
      patients with pneumonia are frequently oligosymptomatic. Quite often, mental
      confusion may be the only clinical symptom. Physical and chest radiograph
      examination have specific and important pitfalls. Mental confusion as a surrogate
      marker of severe sepsis should be added to the criteria for assessing the
      severity of disease. Pneumonia in the elderly is associated with a considerably
      increased mortality, but age does not appear to be an independent predictor of
      death. The disease continues to be the old man's friend: survivors of a pneumonia
      episode are more likely to die during follow-up as compared to controls.
      Antimicrobial treatment in the elderly should follow a risk-adopted approach.
      When selecting antimicrobial agents for the treatment of the elderly,
      peculiarities in pharmacokinetics, drug interactions and side effects should be
      considered. The rate of radiographic clearance is inversely correlated with age.
      All elderly individuals are candidates for vaccination against pneumococci and
      influenza, particularly in the presence of cardiopulmonary comorbidity and any
      degree of immunosuppression.

PMID- 10944815
TI  - Distribution of patients with Wilson disease carrying the H1069Q mutation in
      Austria.
AB  - BACKGROUND/AIMS: More than 100 different mutations of the Wilson disease (WD)
      gene have been reported so far, but only the H1069Q mutation is frequently found
      in patients of North and East European origin. We wanted to know if there is a
      connection between the migration pattern in Central Europe and the geographical
      distribution of this mutation in Austria. METHODS: One hundred and nine patients
      (91 index patients and 18 asymptomatic siblings) with WD diagnosed in Austria
      were included in this study. Eighty-one of the 91 index patients were born in
      Austria. Evaluation criteria included the place of birth of each member of the
      study group, as well as of his parents and grandparents. RESULTS: Out of the 81
      index patients born in Austria, 72 were tested for the H1069Q mutation. Twelve
      (16.7%) were homozygous carriers of the H1069Q mutation, 29 (40.3%) were compound
      heterozygous and 31 (43.0%) had an unknown mutation on both chromosomes. Eight of
      the twelve H1069Q homozygotes were born close to the northeastern border of
      Austria (neighboring the Czech Republic, Slovakia and Hungary). Compound
      heterozygous patients showed a more variable geographical distribution with
      respect to their birthplace. The patients with unknown mutation were scattered
      all over Austria. CONCLUSION: These data provide further evidence that the H1069Q
      mutation originates from Eastern Europe. In patients from these countries the PCR
      based testing for this mutation may be useful for differential diagnosis and
      family studies.

PMID- 10944816
TI  - [Microcirculatory changes over the tender points in fibromyalgia patients after
      acupuncture therapy (measured with laser-Doppler flowmetry)].
AB  - Apart from widespread pain which is the main symptom of fibromyalgia, a great
      variety of functional and vegetative changes occur in the presence of this
      disease. Such changes include alterations in microcirculation, which may cause
      pain. A preliminary study demonstrated a reduction in regional blood flow above
      "tender points" in fibromyalgia patients compared with healthy controls. A
      consensus statement of the National Institutes of Health (NIH) states that
      acupuncture is a sufficient adjuvant method to treat patients with fibromyalgia.
      The aim of the present study was to determine parameters to measure the
      effectiveness of a specific treatment modality (such as acupuncture) in addition
      to the patient's subjective assessment of acupuncture treatment. Twenty patients
      with fibromyalgia according to the ACR and the Muller/Lautenschlager criteria
      were included in the study. Acupuncture was performed and adapted to individual
      needs in accordance with a specific protocol. Five representative "tender points"
      were examined before and after therapy by laser flowmetry, and the data were
      compared with temperature measurement and dolorimetry. Increased blood flow was
      registered above all "tender points" after acupuncture. Skin temperature had
      increased in 10/12 tender points by a mean of 0.45 degree C. The number of
      "tender points" were reduced from 16.1 to 13.8 after therapy. The pain threshold
      increased in 10/12 "tender points". These data suggest that acupuncture is a
      useful method to treat patients with fibromyalgia. Besides normalisation of
      clinical parameters, the improvement in microcirculation above "tender points"
      may alleviate pain.

PMID- 10944817
TI  - [Influence of risk factor "hot foods over 37 degrees Celsius" on oral flora and
      the pathogenesis of gingivitis and periodontitis].
AB  - Austrian law prescribes that hot food and beverages must be served at a minimum
      temperature of 75 degrees C. Within a group of 50 volunteers, we studied hot food
      at a temperature higher than 37 degrees C as a risk factor for the pathogenesis
      of gingivitis and periodontitis. In the first part of the investigation the
      effects of heat on bacterial growth in the mouth were evaluated. Bacterial growth
      was significantly reduced after drinking hot tea (70 degrees C) (p < 0.001). The
      ability of the volunteers to estimate the temperature of a direct heat stimulus
      in the mouth was tested in the second part of the study. 82% of the volunteers
      underestimated the temperature of tea (70 degrees C) by about 15 degrees C. In
      the third part of the study the periodontal state of the volunteers was
      determined by index measurements. Moreover, eating behaviour was assessed by a
      questionnaire. No statistically significant correlation between eating behaviour
      (hot/cold) and periodontal inflammation was found.

PMID- 10944818
TI  - [Edrophonium chloride (Tensilon) test: a safe method in diagnosing myasthenia
      gravis].
AB  - OBJECTIVE: To evaluate the safety of edrophonium chloride in the course of the
      Tensilon test by measurement of hemodynamic and ECG parameters and the
      observation of adverse events. METHODS: 25 patients with known or suspected
      myasthenia gravis were included in an open, prospective study concerning the
      performance of the Tensilon test. Blood pressure, heart rate, continuous ECG and
      adverse events were recorded 10 minutes following intravenous application of
      Tensilon. RESULTS: Blood pressure and heart rate did not change significantly
      during the observation period. One patient on beta-blockers developed a grade I
      AV block. Self-limiting adverse events of short duration were observed in 11
      patients. Serious adverse events such as syncope or hemodynamic deterioration did
      not occur. CONCLUSION: The Tensilon test appears to be a safe procedure. A
      detailed clinical cardiac history, the history of medication and twelve lead ECG
      recordings should be documented in all patients undergoing the Tensilon test.
      Patients with a history of dysrhythmia receiving digitalis, beta-blocking agents
      or Ca antagonist therapy should be managed with special care, as Tensilon
      enhances vagal effects.

PMID- 10944819
TI  - Complete remission of cryoglobulinemic glomerulonephritis (HCV-positive) after
      high dose interferon therapy.
AB  - We report the case of a 64-year old woman with hepatitis C virus infection, mixed
      cryoglobulinemia type II (IgG + IgM kappa) and cryoglobulinemic
      glomerulonephritis. The patient was treated with the standard dose of recombinant
      interferon alpha-2b (3 million units 3 times a week) for one year, resulting in
      complete clinical remission and undetectable levels of serum hepatitis C virus
      RNA. AST and ALT normalized and proteinuria decreased from 2.78 to 0.98 g/day.
      However, a relapse occurred when therapy was stopped. Additional therapy with
      interferon-alpha (5 million units 3 times a week for 9 months) resulted again in
      quick and prolonged remission. The clinical course of our patient showed
      sustained clinical and virologic response after high-dose interferon-alpha
      treatment confirming the usefulness of interferon alpha in treatment of patients
      with cryoglobulinemic glomerulonephritis. Our observation is in agreement with
      others, suggesting that recommended standard dosage and duration of initial
      treatment with interferon alpha should be re-evaluated. Although our patient had
      sustained virologic and clinical response after interferon alpha monotherapy,
      recent studies clearly support combination therapy of interferon alpha and
      ribavirin for treatment of chronic HCV infections.

PMID- 10944820
TI  - [Conception and evaluation method of QOL (quality of life) in allergic diseases-
      mainly on bronchial asthma].

PMID- 10944821
TI  - [Measurement of the air dispersion cedar pollen number and its application].

PMID- 10944822
TI  - [Ovalbumin sensitization affects nonadrenergic noncholinergic relaxation response
      on guinea-pig tracheal smooth muscle].
AB  - We investigated the effects of anaphylactic challenge on nonadrenergic
      noncholinergic (NANC) relaxation response to electrical field stimulation (EFS)
      or to aminophylline in sensitized guinea pig tracheal smooth muscles. An
      anaphylactic challenge with ovalbumin (OA) reduced the relaxation response to EFS
      (20 V. 5 Hz. 300 pulse. duration 1 msec.), but the relaxation response to
      aminophylline was not affected by OA exposure. NG-monomethyl L-arginine, a nitric
      oxide (NO) synthesis inhibitor, reduced the relaxation response to EFS in the OA
      sensitized guinea pig. While the relaxation response to EFS on the sensitized
      guinea pig tracheal smooth muscle was significantly attenuated compared with that
      on the non-sensitized guinea-pig, there was no significant difference between the
      tracheal strip of OA challenge group and that of control group in sensitized
      guinea-pig under the existence of NO synthesis inhibitor. These results suggest
      that the attenuation of NANC relaxation response associated with sensitization
      plays an important role in airway hyperreactivity and is responsible for the
      decrease in NO amount.

PMID- 10944823
TI  - [A questionnaire survey on the self-assessment to the asthmatic treatment in
      Saitama Prefecture: results from 2825 cases].
AB  - The aim of this study was to survey the self-assessment to the treatment of adult
      bronchial asthmatics in Saitama prefecture. A questionnaire on daily symptoms and
      medications was distributed to 2825 adult asthmatic subjects who were treated at
      125 hospitals/clinics in Saitama prefecture between September 15th and October
      30th 1998. More than half (52.7%) of patients described that their general
      condition of asthma was poorly controlled. Even among the patients described that
      their condition was good or fair, 30.2% of them had some asthmatic symptoms such
      as shortness of breath or nocturnal awakening. Although inhaled corticosteroids
      were used in 66.2%, the ratio of patients who used spacer and kept drug
      compliance as prescribed were 59.6% and 45.8%, respectively. According to the
      physician's reports, cysteinyl leukotriene antagonist was used in 35.7%, which
      was comparable to the total of another anti-allergic drugs (37.3%). These results
      suggest that more than half of asthmatic patients in Saitama prefecture were not
      satisfied with their conditions of the disease control. Furthermore, more
      thorough education on the technique and compliance of inhaled corticosteroids
      would be required.

PMID- 10944824
TI  - [Serum levels of NO products, IL-8, RANTES and eotaxin in infantile patients with
      atopic dermatitis].
AB  - Inflammatory mechanisms play an important role in the pathogenesis and the
      expansion of the skin lesion in AD. The serum levels of NO product, IL-8, RANTES
      and eotaxin, which are considered to an index of the inflammatory response, were
      measured in infants diagnosed as AD. The serum levels of NO product, RANTES and
      eotaxin were higher in the infantile AD patients with the systemic skin lesion
      compared with controls. The higher levels of NO product were shown with the
      expansion of the skin lesion. In AD patients, the serum levels of NO product were
      significantly correlated with the serum levels of eotaxin (r = 0.615, p < 0.001).
      These results suggest that NO product bears an important function in the allergic
      inflammation, which is concerned with the lesion expansion of the infantile AD
      patients and may be an index of the allergic inflammation.

PMID- 10944825
TI  - [The effect of DPT and BCG vaccinations on atopic disorders].
AB  - METHODS: To examine the relationship between DPT and BCG vaccinations and
      development of atopic diseases, we studied on 143 children resident of the island
      of Kodushima, Tokyo Japan. This study dealt with the entire population of 0-3
      years old (82), all of the first graders of the elementary school (31) and all of
      the first graders of the junior high school (30) on the Island. RESULTS: Among
      the 82 children aged 0-3, out of the 39 who received DPT vaccination, 10 (25.6%)
      suffered from bronchial asthma and this ratio was significantly higher than among
      the children who have not received DPT vaccination (1 in 43, 2.3%), (p < 0.01).
      This was also the case concerning atopic dermatitis (7 in 39, 18.0% vs 1 in 43,
      2.3%) (p < 0.05). The same trend was also observed if three diseases (bronchial
      asthma, allergic rhinitis and atopic dermatitis) were combined (22 in 39, 56.4%
      vs 4 in 43, 9.3%) (p < 0.01). As to the context of BCG vaccination, there were no
      cases with atopic disorders among the tuberculin positive first graders of the
      elementary school. No such relations, however, were observed among the first
      graders of the junior high school at all. FINDINGS: From these results, we
      conclude that DPT vaccination has some effect in the promotion of atopic
      disorders, while successful BCG vaccination inhibits the development of atopic
      disorders, although the preventive effect of BCG may not last for many years.

PMID- 10944826
TI  - [Efficacy of sustained-released theophylline on peak expiratory flow rate in
      asthmatic patients].
AB  - Nocturnal worsening is an important problem in asthma management. We evaluated
      the efficacy of two sustained-released theophylline formulations, administered
      twice-a-day (TD) and once-a-day (UP). In 20 asthmatic patients with low peak
      expiratory flow rate (PEF) in the morning (< 80% of predicted) administered TD
      (mean dose 475 mg/day) for 2 weeks, we evaluated PEF, diurnal variability of PEF,
      symptom score, results of spirometry and serum theophylline concentration (STC)
      and then changed theophylline, from TD to UP (mean dose 470 mg/day) for 2-4
      weeks. PEF in the morning was higher during the UP period (mean +/- SD: 335 +/-
      110 L/min) than during the TD period (mean +/- SD: 308 +/- 95 L/min) (p < 0.05),
      and diurnal variabirity of PEF was lower during the UP period (17.1 +/- 8.0%)
      than TD period (22.9 +/- 13.4%) (p < 0.05). However, there were no changes in PEF
      at night or daytime, symptom score, spirometry parameters or STC during the study
      period. The improvement in morning PEF observed in this study was consistent with
      the differences in pharmacokinetics between the two theophylline formulations.
      Morning PEF was increased during the UP period, probably because STC in the early
      morning during the UP period was higher than STC during the TD period.

PMID- 10944827
TI  - [Inhibitory effect of suplatast tosilate on eosinophil migration].
AB  - Suplatast tosilate has been shown to inhibit generation of Th2-type cytokines in
      vitro and used in the treatment of allergic diseases. Although the exact
      mechanism remains unknown, this compound attenuates the eosinophil infiltration
      in the asthmatic airway. In the present study, we examined whether suplatast
      tosilate directly modulates eosinophil migration in response to inflammatory
      mediators in vitro. Suplatast did not modify the spontaneous migration of
      eosinophils. On the other hand, eosinophil migration in response to PAF (1
      microM) was significantly inhibited by 1 microM suplatast. Similarly, IL-5 (100
      pM)-induced eosinophil migration was inhibited by 1 microM suplatast. These
      results suggest that suplatast tosilate inhibits eosinophil locomotion in
      response to PAF or IL-5 and thereby attenuates infiltration of the cells in
      allergic inflammation.

PMID- 10944828
TI  - Changing pattern of intracranial lesions.

PMID- 10944829
TI  - Intracranial neoplasms in Ibadan, Nigeria.
AB  - OBJECTIVE: To determine the pattern of histopathological variants of intracranial
      neoplasms, relative distribution of the variants in the age groups and also to
      determine the gender differences that exist in these tumours. DESIGN: Case
      control study. SETTING: Department of Pathology, University College Hospital,
      Ibadan, Nigeria. PATIENTS: Two hundred and ten histologically confirmed cases of
      intracranial neoplasms seen during eleven-year period (1980 to 1990) were
      analysed. INTERVENTIONS: Slides of tumours stained with haematoxylin and eosin,
      reticulin and phosphotungstic acid haematoxylin. RESULTS: Two hundred and ten
      intracronial neoplasms comprising 172 primary and 48 secondary neoplasms were
      seen. One hundred and thirty five neoplasms occurred in adults and 75 in
      children. There was no gender difference, the ratio being 1:1. Gliomas accounted
      for the largest group of tumours followed by metastases to the brain. Of the
      gliomas, astrocytoma was the commonest. Craniopharyngiomas were found to be
      common in children. Germ cell tumours were found to be uncommon. CONCLUSION:
      Gliomas are the commonest group of intracranial neoplasms in both adults and
      children. This is followed by metastatic tumours. Tumours of the sella turcica
      are predominantly found in children. Involvement of the brain in disseminated
      Burkitt's lymphomas is predominantly found in Africans as the Burkitt's tumour is
      uncommon in non Africans.

PMID- 10944830
TI  - Predictive indices in traumatic intracranial haematomas.
AB  - OBJECTIVE: To identify factors of predictive value in the early diagnosis of
      traumatic intra-cranial haematomas (ICH). DESIGN: A retrospective study of
      patients with positive exploratory burr hole findings of ICH. SETTING: Jos
      University Teaching Hospital, Nigeria between January 1988 and December 1998.
      PATIENTS: Two hundred and six patients. MAIN OUTCOME MEASURES: The demographic
      data of patients, duration of presentation, Glasgow Coma Scale (GCS), causes,
      clinical features and mortality characteristics of patients were analysed.
      RESULTS: There was a bi-modal age distribution with a mean of 26 years.
      Male:female ratio was 2:1. Vehicular accidents accounted for 72% of ICH and falls
      for 22%. Sixty seven per cent recorded a GCS of 14-15 out of a total of 175 GCS
      recorded. A brief history of loss of consciousness was obtained in 33%, headaches
      49%, deterioration in conscious level 91%, seizures 53%, cranial nerve deficits
      11% and hemiplegia in 22%. Significant lateralising signs occurred within 72
      hours. Extra-dural haematomas constituted 37% and were associated with cranial
      vault fractures in all cases. Subdural haematomas constituted 60%, with skull
      fractures in eight per cent and intracerebral haematomas occurred in three per
      cent. A mortality of seven per cent was recorded for all patients with ICH.
      CONCLUSION: Traumatic ICH is associated with raised intracranial pressure in many
      patients.

PMID- 10944831
TI  - Hepatitis B and C virus infections and liver function in AIDS patients at Chris
      Hani Baragwanath Hospital, Johannesburg.
AB  - BACKGROUND: Impaired liver function tests and co-infection with hepatitis viruses
      in AIDS patients are common in western countries. OBJECTIVE: To assess liver
      function and prevalence of co-infection with hepatitis B and hepatitis C viruses
      in AIDS patients at Chris Hani Baragwanath Hospital. DESIGN: A prospective study.
      SETTING: Chris Hani Baragwanath Hospital, Johannesburg, South Africa. PATIENTS:
      One hundred consecutive patients with AIDS admitted to Chris Hani Baragwanath
      Hospital. RESULTS: There were 52 males and 48 females aged 16 to 54 years (mean +
      SD: 34.6 + 7.5 years). The results of laboratory test were as follows: LFTs:
      bilirubin 11.8 (+15.6) mumol/l; AST: 79.6 (+/- 116.6) iu/L; alkaline phosphatase:
      204.3 (+/- 237.4) i mu/L; albumin: 23.9 (+/- 6.2) g/l; CD4+ lymphocytes: 141.5
      (+/- 168.6) microliters; CD8+: 666.9 (+/- 618.3) microliters; HBV - HbsAg: 6
      (6%); HbsAg + eAg: 3 (3%); previous disease (Anti HBs and/or anti HBc): 35%, HCV:
      1(1%). CONCLUSION: Liver function tests were impaired in the majority of patients
      with AIDS (93%) in our setting. Evidence of previous and present HBV infection
      was present in 41%. This is different from what is observed in western countries
      (90-95%). The results also suggest that patients here acquired HBV infection
      while still immuno competent. HCV infection was rare.

PMID- 10944832
TI  - Supernumerary lumbar vertebrae in human skeletons at the Galloway Osteological
      Collection of Makerere University, Kampala.
AB  - OBJECTIVE: To find out the number of other skeletons in the Galloway collection
      that have a variation of six lumbar vertabrae. DESIGN: A descriptive cross
      sectional study. SETTING: Department of Anatomy, Faculty of Medicine, Makerere
      University, Kampala. MATERIALS: Five hundred and ninety one skeletons in the
      Galloway Osteological Collection housed in the basement of the Department of
      Anatomy, Faculty of Medicine, Makerere University. INTERVENTIONS: The skeletons
      were examined. Those found to have six lumbar vertebrae were scrutinised further.
      A recount was done of the cervical and thoracic vertebrae in order to ascertain
      the identity and number of the lumbar vertebrae. Some of the skeletons were x
      rayed and photographed to illustrate the finding and the manner in which the
      transverse processes of the sixth lumbar vertebrum articulated with the alar of
      the sacrum. RESULTS: Out of the 591 skeletons examined, twenty (4%) were found to
      have a sixth lumbar vertebrum. In seven (35%) of these, the transverse processes
      of the sixth lumbar vertebrum were found to be bilaterally articulated with the
      alar of th sacrum and in another five (25%) only the left was. In the remaining
      eight (40%), the transverse processes did not articulate with the alar of the
      sacrum at all. Right unilateral articulation between the transverse process and
      the alar of the sacrum was not observed in any of the twenty skeletons that had
      six lumbar vertebrae. CONCLUSION: In the Galloway osteological collection there
      is a small number of skeletons in which the number of lumbar vertabrae is six
      instead of 5 as is normally the case. In most of them the transverse processes of
      th sixth lumbar vertebrum articulate with the alar of the sacrum through a
      synovial joint (bilateral or unilateral). The above observations have raised
      several questions in the mind of the author regarding the mechanism of causation
      of the variation and its clinical and functional implications.

PMID- 10944833
TI  - Bacteriology of chronic otitis media in Dar es Salaam, Tanzania.
AB  - OBJECTIVES: To determine the aetiology of chronic otitis media (COM) in Dar es
      Salaam and to find out the shelf life of boric acid in spirit ear drops (BAISED).
      DESIGN: Cross-sectional study. SETTING: Muhimbili Medical Centre and selected
      primary schools within Dar es Salaam. MAIN OUTCOME MEASURES: Bacterial isolates
      and their sensitivity patterns and shelf life of BAISED. SUBJECTS AND METHODS:
      One hundred and seventy six pus swab specimens obtained from 150 patients with
      COM for more than three months were submitted for culture and antimicrobial
      sensitivity testing in 1997. RESULTS: The isolates included Pseudomonas
      aeruginosa (51.7%), Staphylococcus aureus (17.2%), Proteus mirabilis (13.2%),
      Klebsiella spp. (8.0%), Escherichia coli (5.8%) and unidentified coliforms in
      4.0%. All isolates were sensitive to gentamicin. Sensitivity of Pseudomonas
      aeruginosa and Proteus mirabilis to kanamycin was 98.5% and 100%, respectively.
      P. aeruginosa was sensitive to chloramphenicol, ampicillin and tetracycline by
      58.1%, 10.1% and 8.3%, respectively. Three per cent BAISED inhibited the growth
      of all Pseudomonas aeruginosa even after it has been stored at room temperature
      for six weeks. CONCLUSION: Based on these results, the drug of choice for
      management of COM in Dar es Salaam is gentamicin. However, given its ototoxicity
      effects and the fact that BAISED is effective and affordable, the later should be
      the treatment of choice.

PMID- 10944834
TI  - Chronic osteomyelitis in patients with sickle cell disease.
AB  - OBJECTIVE: To determine the baseline pattern and audit management modalities of
      chronic osteomyelitis in patients with sickle cell disease. DESIGN: A
      retrospective study. SETTING: Jos University Teaching Hospital, Jos, Nigeria from
      August 1993 to July 1997. PATIENTS: Twenty four patients with concomitant chronic
      sickle cell disease. INTERVENTIONS: Fifteen patients had operations; eleven had
      sequestrectomy and curettage while four had incision and drainage. Eight patients
      were treated with antibiotics alone and one patient refused surgery. MAIN OUTCOME
      MEASURES: The demographic data of patients, aetiological agents, culture and
      sensitivity patterns, aetiopathogenesis, treatment modalities and outcome were
      analysed. RESULTS: Twenty four (36.9%) out of 65 patients who had chronic
      osteomyelitis also had sickle cell disease. Male:female ratio was 1.2:1. The peak
      age incidence (37.5%) was in the first decade of life. Seventy five per cent of
      infections were haematogenous. The most frequently isolated organism was
      Staphylococcus aureus (58.8%) while the rest were Gram negative organisms. There
      was no case of Salmonella osteomyelitis. The most sensitive antibiotics were
      gentamicin and the third generation cephalosporins. Twelve patients (50%) had
      good results while eight (33.3%) were still undergoing treatment. Complications
      recorded were persistent discharging sinuses in two cases, recurrence of symptoms
      in one and pathological fracture with non-union in one patient. CONCLUSION:
      Though the incidence of Gram negative organisms in causation of chronic
      osteomyelitis in patients who have sickle cell disease is high (41.2%),
      Salmonella osteomyelitis may be related to endemicity of the organism in a given
      locality.

PMID- 10944835
TI  - Gastric carcinoma at Tikur Anbessa Hospital, Addis Ababa.
AB  - OBJECTIVE: To provide a baseline epidemiologic information on gastric cancer from
      Ethiopia based on hospital data. DESIGN: Prospective study. SETTING: Department
      of Surgery, Tikur Anbessa Hospital, Faculty of Medicine, Addis Ababa University,
      Addis Ababa. SUBJECT: Ninety six patients treated for gastric cancer from 1992
      1996. INTERVENTIONS: Data including demographic and clinical features, pathology
      of the disease and treatment outcome were analysed on 96 of 125 cases of gastric
      cancer. MAIN OUTCOME MEASURES: Duration of symptoms, diagnosis and stage of
      disease at the time of definitive diagnosis, and postoperative mortality.
      RESULTS: Sixty eight patients were males and 28 females. The mean age was 48.2 +/
      12.7 (range 20-73) years. The histopathology was adenocarcinoma with a Laurence
      intestinal type in 89 cases. Majority of the cases (90%) had advanced (stage III
      IV) tumours. More than forty four per cent of cases had resectable lesions.
      Postoperative mortality rate was 18.6%. Twenty seven of the 70 cases operated on
      (57 survived the operations) could be followed up only for less than one year.
      CONCLUSION: This study, although based on the relative frequency in a hospital
      material, indicates that gastric cancer is not rare in Ethiopia. Patients appear
      to present late with advanced cancers.

PMID- 10944836
TI  - Obstructed abdominal hernia at the Wesley Guild Hospital, Nigeria.
AB  - OBJECTIVE: To determine the incidence, pattern and outcome of obstructed
      abdominal wall hernia in a semi-urban and rural community. DESIGN: A proforma was
      drafted to study all consecutive patients operated for obstructed anterior
      abdominal wall hernia over a period of five years. Clinical findings,
      preoperative treatment, operative findings and postoperative outcome were
      documented. SETTING: Teaching hospital located in a semi-urban community
      comprising mostly agrarian population. PATIENTS: A total 110 adult patients with
      obstructed anterior abdominal wall hernia who had operative intervention and
      other postoperative management. RESULTS: There were 110 patients with 111
      obstructed hernias, accounting for 26.4% of all abdominal wall hernias. The age
      ranged from 19-79 years with mean of 49.7 years. Males accounted for 81%.
      Inguinoscrotal hernia was the commonest occurring in 75.7%, 16.2% patients
      presented with inguinal hernia and five patients with femoral hernia. The greater
      proportion of inguinal hernia occurred in female. Eighty seven patients (79%) had
      emergency operations and elective in 23 patients (21%) who had spontaneous
      reduction while awaiting surgery. Ninety two percent of inguinoscrotal/inguinal
      hernia were indirect. Omentum was trapped in 52 hernias (47.%), while in 15
      patients (13.6%), gangrenous bowel segments were discovered. Scrotal oedema was
      the commonest complication accounting for 21%, while wound infection occurred in
      20%. There were three deaths in elderly men with clinical symptoms and signs of
      acute intestinal obstruction and gangrenous bowel segments, accounting for 2.7%
      of the patients. Twenty eight per cent of patients were discharged within the
      first and second postoperative days. Two patients spent 36 and 56 days each in
      the hospital. CONCLUSION: This study showed that 26.4% of abdominal hernia
      presented with obstruction. With inguinoscrotal hernia predominating: male
      accounted for 81% and 13.6% of the obstructed hernia contained gangrenous bowel
      segments. Post-operative complications were common, mortality occurring mainly in
      elderly patients with late presentation.

PMID- 10944837
TI  - Hippurate hydrolysis and Christie, Atkins, Munch-Peterson tests as
      epidemiological diagnostic tools for Streptococcus agalactiae carriage in
      pregnancy.
AB  - OBJECTIVE: To evaluate the Christie, Atkins, Munch-Peterson (CAMP) and hippurate
      hydrolysis reactions as diagnostic tools for Streptococcus agalactiae carriage in
      pregnancy. DESIGN: Observational, analytical case-control study. SETTING:
      Hospital-based study in a primary and a tertiary health care institution.
      PATIENTS: One hundred and six pregnant and 56 non-pregnant (controls) women were
      included in the study. The participants were of different socio-economic status.
      A volunteer sample was used. About 800 subjects were contacted and 162
      participated in the study. RESULTS: The sensitivity of the screening test varied
      from 25% for the CAMP test to 77.78% for the hippurate hydrolysis reaction. The
      specificity was the same for both tests at (50%). A significant difference in
      positivity between the CAMP and hippurate hydrolysis reactions (95% confidence
      limit, P < 0.05) was observed. The predictive values of the positive test were
      66.6% (CAMP) and 87.55% (hippurate hydrolysis) while the negative test were
      14.29% (CAMP) and 33.30% (hippurate hydrolysis). Pregnant women had 0.33 chances
      of being GBS carriers with the CAMP compared to 3.5 with the hippurate
      hydrolysis. CONCLUSION: The hippurate hydrolysis test is highly recommended since
      the reagents are easily available and the organism was easily isolated using this
      method. The presence of GBS in the anorectum and endocervix is likely to induce
      systemic and local immunity in the female genital tract. This can contribute to
      the development of a mucosal vaccine for GBS diseases.

PMID- 10944839
TI  - Specific psychiatric morbidity among diabetics at a Nigerian General Hospital.
AB  - BACKGROUND: In Nigeria, with a rising incidence of diabetes mellitus (DM), there
      are no controlled studies of specific psychiatric morbidity among sufferers.
      OBJECTIVE: To assess the prevalence of specific psychiatric disorders and general
      cognitive impairment in patients with diabetes mellitus. METHOD: Using Wing's
      Present State Examination and the Mini-Mental State Examination, we assessed the
      prevalence of specific psychiatric disorders and cognitive impairment among 100
      DM patients attending an out-patient clinic, in comparison with a matched non
      clinic sample; and examined the relationship between psychiatric morbidity and
      clinical variables. RESULTS: They were predominantly males (66%), mean age 43.0
      years, mean duration of illness, 7.7 years and in low level occupations. Only 11
      of the patients had sexual dysfunction (11%) and psychiatric symptoms (31%).
      Psychiatric diagnosis (ICD-10) were, generalised anxiety (6%) and mild depressive
      disorder (4%). Two had subjective memory disturbance. Insulin-dependent patients
      had significantly more widespread psychiatric symptoms than the non-insulin
      dependent. Psychiatric symptomatology was significantly associated with low
      occupational status, duration of illness and sexual dysfunction. CONCLUSION:
      Health education, subsidizing the cost of treatment, and physicians' sensitivity
      to the emotional condition of patients, will help to relieve psychic distress and
      make for more adequate management.

PMID- 10944838
TI  - Effect of improved stoves on prevalence of acute respiration infection and
      conjunctivitis among children and women in a rural community in Kenya.
AB  - OBJECTIVES: To estimate the effect of improved stoves on the prevalence of ARI
      and conjunctivitis among children aged below five years and women aged between 15
      and 60 years. METHOD: A field trial or intervention study design, in which
      cluster and random sampling were used to recruit households with improved stoves.
      Nearest households with traditional three-stone stoves were recruited as
      controls. Prevalence of ARI and conjunctivitis among the study subjects was
      estimated by clinical evaluation and physical observation, and by history
      (including clinical and socioeconomic information), and compared between the two
      study groups. RESULTS: The prevalence of ARI among children aged below five years
      and among women aged between 15 and 60 years were significantly higher in
      households with the traditional three-stone stoves than in those with the
      improved stove chi 2 = 31.45 rho = 0.00000, relative risk = 2.6, C.I. 1.86,3.63,
      and chi 2 = 30.13, rho = 0.00000, Relative Risk = 2.8, C.I. 1.93, 4.06,
      respectively). Similarly the prevalence of conjunctivitis among children aged
      below five years and among women aged between 15 and 60 years were significantly
      higher in households with traditional three-stone stoves than in those with the
      improved stoves (c2 = 24.18, p = 0.00000, Relative Risk = 3.3, C.I. 2.05,5.32,
      and chi 2 = 7.6, rho = 0.0057, Relative Risk = 3, C.I. 1.38, 6.54, respectively).
      CONCLUSION: Prevalence of ARI and conjunctivitis among children aged below five
      years and also among women aged between 15 and 60 years in households with the
      traditional three-stone stoves was significantly higher than that in households
      with improved stoves.

PMID- 10944840
TI  - Factors affecting condom use among South African university students.
AB  - OBJECTIVE: To investigate factors affecting condom use among South African
      university students. DESIGN: Cross-sectional survey. SETTING: Department of
      Psychology, University of the North, South Africa. PARTICIPANTS: One hundred and
      forty six female and sixty first year male psychology students, mean age 20.9
      years (SD = 3.4), with a range from 17 to 34 years. MAIN OUTCOME MEASURES: Sexual
      activity and condom use (6 items), A 16-item AIDS Health Belief Scale and a 28
      item Condom Use Self-Efficacy Scale. RESULTS: Almost one third (29.2%) of the
      sample reported never using condoms, 35.4% always, 19.8% regularly and 8.5%
      irregularly in the past three months. Perceived barriers were associated with
      increasing age and reduced condom use intentions. In addition, perceived
      susceptibility was associated with past condom use. The total AIDS Health Belief
      was not related with age, gender, past condom use and condom use intentions. Self
      efficacy of condom use was associated with decreasing age, past condom use and
      condom use intentions but not with gender. CONCLUSION: Findings have relevant
      implications and are discussed in the context of developing an educational or
      intervention programme.

PMID- 10944841
TI  - Pulmonary response of mice to aqueous cotton dust extract.
AB  - OBJECTIVE: To determine the pulmonary response of mice to acute exposure of
      aqueous cotton dust extract (CDE). DESIGN: CDE was made from a standard cotton
      mill dust. Under mild anaesthesia, 0.05 ml of CDE was instilled intratracheally
      in balb/c mice. The same volume of sterile isotonic saline was instilled in
      controls. After 1, 5 and 10, days animals were given an overdose of pentobarbital
      by intraperitoneal injection, and the upper thorax was opened to expose the
      trachea. An incision was made and cannulae was inserted. Bronchoalveolar lavage
      (BAL) was done by instilling, phosphate buffer saline. Total and differential
      counts were done. The lavage supernatant was assayed for protein. SETTING: The
      laboratory of Division of Pulmonary and Critical Care Medicine, Duke University
      Medical Center, USA. ANIMALS: Balb/c mice. MAIN OUTCOME MEASURES: Post-exposure
      acute effects at bronchoalveolar level. RESULTS: Total and differential cell
      counts in BAL fluid were significantly higher in CDE exposed compared to controls
      (P < 0.01). The total mean values (expressed as cells x 10(4)) after exposure for
      days 1, 5 and 10 were 193.4 +/- 8.6, 177.8 +/- 7.7 and 113.5 +/- 6.4 respectively
      versus controls (41.6 +/- 3.4). Differential counts (cell no. x 10(4)) revealed
      124.3 +/- 6.8, 94.2 +/- 7.9, 19.9 +/- 3.5 polymorph neutrophils (PNM) and 67.3 +/
      7.1, 81.6 +/- 9.4, 90.2 +/- 8.6 macrophages (AM) on days 1, 5 and 10
      respectively compared to controls 2.8 +/- 2.3 (PMN) and 37.2 +/- 1.1 (AM).
      Analysis of protein (mg/ml BAL fluid) demonstrated a significant increase on
      exposure for days 5 and 10 (0.8 +/- 0.05 and 0.9 +/- 0.6 respectively versus
      controls, 0.09 + 0.01, p < 0.01). CONCLUSION: Acute exposure to CDE causes influx
      into the air spaces of inflammatory leukocytes accompanied by an increase in lung
      permeability (evidenced by the presence of protein in BAL fluid). In cotton mill
      workers, the above factors may contribute to the development of chronic
      byssinosis by as yet undefined agent(s) in cotton dust.

PMID- 10944842
TI  - Trichorhinophalangeal syndrome type II: case report.
AB  - Patients with the trichorhinophalangeal syndrome type II, also known as the
      Langer-Giedion syndrome, may present to the health care-givers or physicians in
      various specialties and need to be recognised in order that accurate diagnosis,
      management and counselling about prognosis and recurrence risks may be carried
      out. A case of young male with this condition is presented.

PMID- 10944843
TI  - Forensic medicine in Kenya: a personal view.

PMID- 10944844
TI  - [Novel Ins(1,4,5)P3 binding protein and GABA-A receptor signaling].

PMID- 10944845
TI  - [Usefulness of preadmission autologous blood donation and intraoperative
      autotransfusion using the "cell saver" for the patients with abdominal aortic
      aneurysm repair].
AB  - To evaluate the effectiveness of preadmission autologous blood donation (PABD)
      and intraoperative autotransfusion (IAT) in reducing the homologous transfusion
      requirement of abdominal aortic aneurysm (AAA) resection, we retrospectively
      reviewed 232 AAA cases from January 1991 to December 1999. The patients were
      separated into three groups. The group I (n = 101) received no PAPD and IAT. The
      group II (n = 58) received only IAT. The group III (n = 73) received both PAPD
      and IAT. Surgical data indicating operative time and intraoperative blood loss
      did not differ among the three groups. However, the incidence of requirement for
      homologous transfusion in group III (19.2%) is significantly less than those of
      group I (63.4%) or group II (51.7%), although there was no significant difference
      between group I and group II. We concluded that the combination of PAPD and IAT
      are useful for reducing the incidence of requirement for homologous transfusion
      in the patients with aneurysmal resection.

PMID- 10944846
TI  - [Quantitation of mRNA in micro-samples of the brain by competitive PCR: analysis
      of expression of interleukin-1 beta mRNA in rat hypothalamus and hippocampus
      after inflammatory or non-inflammatory stress].
AB  - Changes in the expressions of interleukin-1 beta (IL-1 beta) mRNA in the rat
      brain were investigated during inflammatory or non-inflammatory stress. We
      utilized competitive reverse transcription PCR (RT-PCR) to quantitate precisely
      the minute amount of IL-1 beta mRNA in small tissues which were micro-punched out
      from discrete sites in the brain. Intraperitoneal injection of lipopolysaccharide
      (100 micrograms/kg) caused a widespread and high elevation of IL-1 beta mRNA in
      the hypothalamus, hippocampus and cerebral cortex. Immobilization stress
      significantly increased IL-1 beta mRNA only in the hypothalamus, when examined in
      the brain block samples, which reached a peak 30 minutes after the start of
      stress. However, examination of the small tissues punched out from discrete sites
      in the brain revealed a profound elevation of IL-1 beta mRNA in the CA1 region of
      the hippocampus and in all the hypothalamic nuclei examined 30 minutes after the
      start of immobilization stress, but not in the CA3 region and the dentate gyrus
      or cerebral cortex. The method shown in this report proved to be useful and may
      be applied to quantify the low amount of mRNA in the small areas in the brain.

PMID- 10944847
TI  - Glucose-6-phosphatase gene mutations in Taiwan Chinese patients with glycogen
      storage disease type Ia.
AB  - Glycogen storage disease type Ia (GSD Ia) is caused by a deficiency of glucose-6
      phosphatase (G6Pase) activity. Eighteen GSD Ia families were studied for G6Pase
      gene mutations. Thirty-two mutations were found in 36 GSD Ia chromosomes: 16 were
      727 G-->T (44.44%); 13 were R83H (327 G-->T; 36.11%); 1 was 341delG; 1 was
      933insAA; and 1 was 793 G-->T. The 727 G-->T and R83H mutations together
      accounted for 80.56% (29/36) of the GSD Ia chromosomes. These two mutations were
      easily examined by polymerase chain reaction-based methods, and the prenatal
      diagnosis of a non-affected fetus was successfully made. The 727 G-->T mutation
      is the predominant mutation in Japanese GSD Ia patients, but is rarely seen in
      Western counties. The 727 G-->T mutation is also the most prevalent mutation in
      Taiwan Chinese, although the incidence is not as high as in Japan.

PMID- 10944848
TI  - Structural and functional study of K453E mutant protective protein/cathepsin A
      causing the late infantile form of galactosialidosis.
AB  - To clarify the molecular basis of the late infantile form of galactosialidosis,
      we characterized a defective protective protein/cathepsin A (PPCA) gene product
      with the K453E mutation newly found in an Arabic patient with this disease.
      Immunocytochemical, expression, and metabolic studies revealed that the precursor
      PPCA was synthesized but not processed to the mature form, and it was degraded in
      the mutant. A structural model of the mutant PPCA was constructed by amino acid
      substitution of 453glutamic acid for lysine in the crystal structure of the wild
      type PPCA precursor reported. The results show that the K453E mutation is located
      at the dimer interface of the PPCA and reduces the hydrogen bond formation in the
      dimer. This structural change may cause instability of the PPCA dimer.

PMID- 10944849
TI  - Detection of genetic variation in Indian population groups using a novel
      minisatellite probe and finding relationships through tree construction.
AB  - Genetic variation in HaeIII-digested genomic DNA samples from different
      individuals belonging to population groups from Bengal, Uttar Pradesh (UP),
      Punjab, and South India was assessed at hypervariable loci, using a minisatellite
      probe, pBA1.2 (accession number, AF 157691), the repeat unit of which was 24 mer
      long and rich in G-bases. Comparison of DNA profiles between individuals showed a
      very low probability of band sharing, which ranged from 0.18 to 0.24. A
      dendrogram, based on Nei's genetic distance, constructed by the neighbor-joining
      method, showed the formation of separate clusters by both South Indian and non
      Indian samples, whereas the construction of a dendrogram based on the Unweighted
      pair group method arithmetic average (UPGMA) method with Jaccard's similarity
      coefficient at the individual level led to the formation of several small
      clusters which were interleaved; also, the subgroups for each of the populations
      were intermingled with the subgroups for the other populations. A separate
      analysis was carried out to check the consistency of the proximity between
      different individuals forming a cluster and between those individuals who were in
      the vicinity of two clusters. The dendrograms thus obtained did not change the
      relationship between the individuals from all the populations studied. Despite
      the distinct clustering observed in the population group comparison, a probable
      admixture was reflected in the finding that some individuals belonging to one
      population group were dispersed or embedded within a cluster generated by the
      individuals of another population group, when a minute dissection of the data for
      generating a tree at the individual level was carried out.

PMID- 10944850
TI  - Genomic structure and chromosomal mapping of the human site-1 protease (S1P)
      gene.
AB  - Site-1 protease (S1P) is a subtilisin-related enzyme that cleaves sterol
      regulatory element-binding proteins (SREBPs) in the lumen of endoplasmic
      reticulum, thereby initiating the release of transcriptionally active NH2
      terminal fragments of SREBPs from membranes. In the experiments reported here, we
      localized the human S1P gene to chromosome 16q24 by fluorescent in situ
      hybridization and radiation-hybrid mapping, and determined its genomic structure.
      This gene is more than 60 kb long and contains 23 exons and 22 introns. Its
      transcription-initiation site within exon 1 is separate from the initiation codon
      in exon 2. Analysis of the exon/intron structure revealed that the S1P gene
      consists of a mosaic of functional units: exon 1 encodes the 5' non-translated
      region; exon 2 encodes the NH2-terminal signal sequence; and exons 2 and 3 encode
      the pro-peptide sequence that is released when S1P is self-activated by
      intramolecular cleavage. Exons 5-10 encode the subtilisin-homology domain that is
      critical for catalytic activity, and exon 23 encodes the transmembrane region.
      Analysis of the putative promoter region revealed a highly G/C-rich region
      containing a binding site for ADD1/SREBP-1, as well as Sp1 and AP2 sites.
      Therefore, expression of the S1P gene may be under the control of SREBP-1, a key
      regulator of the expression of genes essential for intracellular lipid
      metabolism. Our data establish a basis for investigations to detect molecular
      variants in this gene that may alter levels of plasma lipoproteins and/or
      otherwise disrupt intracellular lipid metabolism.

PMID- 10944851
TI  - Carrier detection and prenatal diagnosis of hemophilia A in a Korean population
      by PCR-based analysis of the BclI/intron 18 and St14 VNTR polymorphisms.
AB  - We have undertaken this study to identify the usefulness of polymerase chain
      reaction (PCR)-based analysis of DNA polymorphisms in the BclI/intron 18 and St14
      variable number of tandem repeats (VNTR) loci for carrier detection and prenatal
      diagnosis of hemophilia A in the Korean population. We have analyzed these
      polymorphisms in members of 105 unrelated Korean families with severe hemophilia
      A. The observed heterozygosity rates for the BclI/intron 18 and St14 VNTR
      polymorphisms were 21.0% and 71.3%, respectively. The BclI/intron 18 polymorphism
      was less informative in Koreans when compared with Caucasians and Japanese. The
      allele frequencies for St14 VNTR in Koreans were different from those in
      Caucasians. Compared with Caucasians, there was a markedly higher occurrence of
      low molecular weight alleles in Koreans. The observed heterozygosity for the St14
      VNTR polymorphism in combination with the BclI/intron 18 polymorphism was 81.9%.
      These two polymorphisms were applied to determine the carrier status of 107 women
      from 65 unrelated families, and to assess fetal status in 37 pregnancies. So far,
      we have experienced one case of misdiagnosis of carriership. Our study
      demonstrated that the PCR-based analysis of the BclI/intron 18 and St14 VNTR
      polymorphisms was useful in the carrier detection and prenatal diagnosis of
      hemophilia A in the Korean population.

PMID- 10944852
TI  - Genetic polymorphism of RhD-negative associated haplotypes in the Chinese.
AB  - The Rh blood group is the most polymorphic human blood group system, and is
      clinically significant in transfusion medicine. Individuals are classified as Rh
      positive and Rh-negative depending on the presence or absence of the D antigen on
      the red cell surface. The RhD-negative trait could be generated by multiple
      genetic mechanisms, which have been shown to be ethnic group-dependent. In this
      study, we evaluated the status of seven RHD-specific exons (exons 3, 4, 5, 6, 7,
      9, and 10) and RH intron 4 in 119 Chinese blood donors, using the sequence
      specific primers polymerase chain reaction (SSP-PCR). Of the 87 individuals who
      were RhD-negative, 52 with the ce/ce, ce/cE, or Ce/ce genotype (60%) lacked the
      above seven RHD exons; 22 with the Ce/Ce or Ce/ce genotype (25%) had all the RHD
      exons examined; 13 with the Ce/ce genotype (15%) carried at least one RHD exon.
      Antigen association analysis suggested the existence of a novel class of RhD
      negative associated haplotypes in the Chinese, tentatively denoted D(nf)Ce. The
      D(nf)Ce haplotype consisted of a normal RHCe allele and a nonfunctional RHD gene,
      which vary depending on the structure of the RHD gene. Among the RhD-negative
      Chinese, the estimated frequencies of the dce, dCe, and D(nf)Ce haplotypes were
      0.7500, 0.0465, and 0.2035, respectively. No statistically significant deviation
      from Hardy-Weinberg equilibrium was observed using this genetic model.

PMID- 10944853
TI  - Association between single nucleotide polymorphisms in the hMSH3 gene and
      sporadic colon cancer with microsatellite instability.
AB  - The association between three single nucleotide polymorphisms (SNPs) in the hMSH3
      gene and sporadic colon cancer with microsatellite instability (MSI) was
      analyzed. Of the three SNPs observed in this population, SNPs at residues 235 and
      693 were novel, while that at residue 3133 was previously described. The SNPs at
      residues 235 and 3133 caused amino acid substitutions, V79I and T1045A,
      respectively. We analyzed the allele frequencies of the three SNPs in samples
      from 19 patients with sporadic colon cancer with MSI and 90 healthy controls. We
      found that the V79 allele frequency was significantly higher in the tumor samples
      than in controls. In addition, the frequency of the G693 allele showed a higher
      trend in the tumor samples than in controls. These results indicated that some
      SNPs in the hMSH3 gene were associated with colon cancer with MSI.

PMID- 10944854
TI  - Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome.
AB  - Rett syndrome is a neurodevelopmental disorder observed almost exclusively in
      girls, and is characterized by autistic tendency, severe mental retardation,
      stereotyped hand movements, seizures, and acquired microcephaly. Recently, the
      MECP2 (methyl-CpG-binding protein 2) gene, mapped on chromosome Xq28, was
      reported to be responsible for Rett syndrome. We performed mutational analysis of
      the MECP2 gene in 26 Japanese patients with Rett syndrome (who were sporadic
      cases), and identified disease alleles in 19 patients. The mutations consisted of
      12 different types including 3 missense, 3 nonsense, and 6 frameshift mutations.
      Of these, 8 mutations are novel. Most of these mutations affect the functional
      domains, methyl-CpG binding domain (MBD), and transcriptional repression domain
      (TRD), and therefore may critically affect the function of MeCP2. The disease
      phenotype of patients with mutations in the MBD tended to be more severe than the
      phenotype of those with mutations in the TRD. We also identified 2 types of
      silent mutations and 4 types of missense mutations as benign variants, and these
      are all novel ones. Most of the nucleotide substitutions involve C-->T
      transitions at CpG hotspots. The novel disease alleles and benign variants of the
      MECP2 gene found in this study should contribute to the establishment of a
      reliable diagnosis of Rett syndrome.

PMID- 10944855
TI  - A novel interstitial deletion of KAL1 in a Japanese family with Kallmann
      syndrome.
AB  - We identified a novel interstitial deletion that spanned from exons 5 to 10 of
      KAL1 in two Japanese brothers with X-linked Kallmann syndrome (KS; MIM no.
      308700). Both brothers had hypogonadism, unilateral renal agenesis, and
      disturbance of the sense of smell, but they had no other neurological
      manifestations, including mental disturbance. Their mother was confirmed to be an
      asymptomatic carrier, by use of a comparative multiplex polymerase chain reaction
      (PCR) analysis. The present patients are further examples of patients with KS
      without mental disturbance caused by a mutation confined to KAL1.

PMID- 10944856
TI  - Molecular and structural studies of Japanese patients with sialidosis type 1.
AB  - To gain insight into the pathogenesis of sialidosis type 1, we performed
      molecular investigations of two unrelated Japanese patients. Both of them are
      compound heterozygotes for base substitutions of 649G-to-A and 727G-to-A, which
      result in amino acid alterations V217M and G243R, respectively. Using homology
      modeling, the structure of human lysosomal neuraminidase was constructed and the
      structural changes caused by these missense mutations were deduced. The predicted
      change due to V217M was smaller than that caused by G243R, the latter resulting
      in a drastic, widespread alteration. The overexpressed gene products containing
      these mutations had the same molecular weight as that of the wild type, although
      the amounts of the products were moderately decreased. A biochemical study
      demonstrated that the expressed neuraminidase containing a V217M mutation was
      partly transported to lysosomes and showed residual enzyme activity, although a
      G243R mutant was retained in the endoplasmic reticulum/Golgi area and had
      completely lost the enzyme activity. Considering the data, we surmise that the
      V217M substitution may be closely associated with the phenotype of sialidosis
      type 1 with a late onset and moderate clinical course.

PMID- 10944857
TI  - Eleven single nucleotide polymorphisms and one triple nucleotide insertion of the
      human TGF-beta III receptor gene.
AB  - We found 11 single nucleotide polymorphisms and one triple nucleotide insertion
      in the cDNA of the human transforming growth factor beta (TGF-beta) III receptor
      gene (TGFBR3) located on 1p33-p32, encoding beta-glycan, a component of the TGF
      beta receptor system. Inside the 5' untranslated region (UTR), a G-->A
      polymorphism was identified at position 311. In the open reading frame (ORF), a
      non-conservative T-->C polymorphism was identified at position 392, and three
      conservative polymorphisms were found at positions 563 (G-->A), 1548 (G-->A), and
      2370 (C-->T). A triple nucleotide insertion (GCA) was identified at position
      1419. Inside the 3' UTR, six polymorphisms were identified: four G-->A, at
      positions 2918, 3055, 3098, and 3355; one T-->A, at position 3183; and one G-->C,
      at position 3966. In addition to these changes, some divergences from the
      published sequence were observed in all 12 chromosomes tested. These included, in
      the ORF, an additional C after position 555, two additional G after position 563,
      and an additional T after position 1388. No T was found at position 1394. The
      alterations translate to a changed amino acid sequence. Inside the 3' UTR,
      additional discrepancies were identified. The discovered changes and
      polymorphisms may be useful for further genetic studies of TGFBR3 receptor
      deficiencies.

PMID- 10944858
TI  - Identification of novel polymorphisms in the AXIN1++ and CDX-2 genes.
AB  - Axin and Cdx-2 play important roles in the tumorigenesis of human liver and
      colon. We have identified seven novel single-nucleotide polymorphisms (SNPs) in
      the AXIN1 gene and three in the CDX-2 gene. The identification of SNPs in these
      cancer-associated genes establishes a basis for future investigations to detect
      losses of heterozygosity in tumors; these SNPs may also provide genetic
      background information associated with cancer risk.

PMID- 10944859
TI  - The C677T mutation in the methylene tetrahydrofolate reductase gene increases
      serum uric acid in elderly men.
AB  - A common mutation, C677T, in the methylene tetrahydrofolate reductase gene
      (MTHFR) reduces the activity of MTHFR and increases total homocysteine levels in
      plasma. Increased homocysteine levels are reportedly associated with high serum
      uric acid levels. The relationship between the MTHFR mutation and uric acid
      metabolism remains unclear, however. To investigate whether the C677T MTHFR
      mutation is a risk factor for hyperuricemia, we performed MTHFR genotyping and
      clinical laboratory determinations, including serum uric acid, in 271 elderly
      Japanese men (age range, 40-79 years; mean, 52.6 years). The mean uric acid
      levels for the C/C, C/T, and T/T genotypes were 5.67, 6.00, and 6.39 mg/dl,
      respectively (P = 0.012). The T/T genotype was more frequent in subjects with
      high uric acid levels than in those with low uric acid levels (P = 0.038). These
      findings suggest that the C677T MTHFR mutation contributed to higher uric acid
      levels in subjects enrolled in this study. In conclusion, the mutation of the
      MTHFR gene may be a risk factor for hyperuricemia in elderly men.

PMID- 10944861
TI  - What is supportive care and why is it important?

PMID- 10944860
TI  - Two deletion mutations in the hydroxymethylbilane synthase gene in two unrelated
      Japanese patients with acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease
      caused by a decreased activity of hydroxymethylbilane synthase (HMBS). Regarding
      the abnormalities of the HMBS gene, many different mutations have been reported
      worldwide; however, few families from Japan have been studied. In this work, we
      investigated the presence of mutations in two unrelated Japanese patients with
      AIP. Mutational analysis was performed using the polymerase chain reaction-single
      strand conformation polymorphism (SSCP) method, followed by DNA sequencing.
      Reliable restriction enzyme cleavage assays were also established for the
      pedigree analyses. Unique SSCP patterns were noted in exons 12 and 15 of the HMBS
      gene. Sequencing revealed different mutations in each patient: a two-base
      deletion of CT at nucleotide 730-731 (730delCT), and also a two-base deletion of
      CA at position 982-983 (982delCA). Both of the deletion mutations lead to
      truncated proteins with an abnormal C-terminus, which would be expected to
      decrease the stability and/or activity of HMBS. Using the cleavage assays, we
      were able to definitively identify gene carriers in the family. This study adds a
      novel mutation to those that have been previously reported, and emphasizes that
      molecular analysis would be very useful not only for the identification of
      asymptomatic gene carriers in the family but also for the detection of ancestral
      founders in porphyria families.

PMID- 10944862
TI  - Evaluation and treatment of chemotherapy extravasation injuries.
AB  - Extravasation of chemotherapeutic vesicant agents can result in significant
      tissue damage, alteration in limb function, and pain. Quality of life for long
      term survivors can be severely impacted by negative sequelae from vesicant
      extravasation. Currently, there is no known preventive therapy. Early detection
      and intervention are paramount to halt tissue damage and reduce the chance of
      permanent disability or disfigurement. This article provides an overview of known
      chemotherapeutic vesicants (mechlorethamine, mitomycin-C, doxorubicin,
      daunomycin, vincristine and vinblastine), associated theories of tissue
      destruction, assessment techniques for peripheral intravenous sites, vascular
      access devices and central venous lines, current treatment strategies, and
      investigational therapies. A brief discussion of the legal implications of
      extravasation injuries and recommended key points for medical record
      documentation are included.

PMID- 10944863
TI  - All the king's horses and all the king's men: pain management from hospital to
      home.
AB  - Pain management in children with cancer continues to be less than adequate in
      most settings. Children in pain often have multiple caregivers, each imposing a
      significant risk to adequate pain management if they are uninformed about the
      principles of pain management and the child's specific pain management regimen.
      This article reviews current pain management guidelines for children, obstacles
      to adequate pain management, and the challenges of managing pain across care
      settings (hospital to home). Using the hospice model of care, case studies are
      presented that illustrate both threats to adequate pain control and the
      coordination of care necessary to ensure consistent pain management between the
      hospital and home. Implications for improvement in pain management between
      settings and future directions for advancing skills and knowledge related to pain
      management in children with cancer are provided.

PMID- 10944864
TI  - Current and future trends in transfusion therapy.
AB  - The increase in intensive treatment for cancer has impacted blood product
      transfusion practices. Transfusion guidelines are primarily institution specific,
      but the general concepts and theories are universal. Blood product screening has
      decreased the risk of transfusion-acquired infections; however, the risk is not
      obsolete. This article reviews current approaches to platelet, white blood cell,
      and red blood cell transfusions, as well as risks associated with these therapies
      (e.g., infection and transfusion-associated graft-versus-host disease). Pertinent
      laboratory studies, patient assessment, blood product administration, and patient
      education is discussed. The current approaches to platelet, white blood cell, and
      red blood cell transfusions are constantly changed and evaluated. Pediatric
      oncology nurses must stay up to date with these changes to provide optimal
      patient care.

PMID- 10944865
TI  - Recombinant tissue plasminogen activator for central venous access device
      occlusion.
AB  - Maintaining and restoring the function of central venous access devices (CVAD) is
      an important component of pediatric oncology nursing care. Until 1999, Abbokinase
      Open Cath (urokinase; Abbott, Abbott Park, IL), a thrombolytic agent was the
      product primarily used to resolve thrombotic occlusions in intravascular devices.
      Changes in the manufacturing process mandated by the FDA have resulted in a lack
      of availability of Abbokinase Open Cath. Recombinant tissue plasminogen activator
      (TPA) has provided an alternative solution for clearing occluded intravascular
      devices. This article reviews the literature supporting the use of TPA for CVAD
      clearance and discusses the process of how to administer the medication. Future
      implications for research about the use of TPA, and its role in the care of CVADs
      are discussed.

PMID- 10944866
TI  - The use of Hepzyme in removing heparin from blood samples drawn from central
      venous access devices.

PMID- 10944867
TI  - A fundamental aspect of supportive care delivery: the nurse's opportunity to
      shape the caring encounter.
AB  - Recent advances in supportive care therapies have significantly contributed to
      the likelihood that a child diagnosed with cancer will be cured. Quantitatively
      recognized supportive care practices, such as central line care management, pain
      control, nutritional support, and blood transfusions are typically identified as
      the major contributors to these improved rates of survival. However, just as
      important are the more qualitative aspects of the nursing care delivery process.
      As a fundamental part of nursing's caring role, the encounter with patients and
      families offers unique opportunities for nurses to participate in the creation of
      a healing environment. Gaining understanding and skill at balancing professional
      relationships, while also knowing the risks of caring, are critical components of
      providing excellent supportive care to pediatric oncology patients and their
      families. The professional caring encounter is a complex and multidimensional
      process. Strategies for developing optimal communication and healthy professional
      caring relationships within the pediatric oncology setting are discussed.

PMID- 10944868
TI  - Controlling particles from construction and demolition: a draft code of practice.

PMID- 10944869
TI  - Justice for women.

PMID- 10944870
TI  - Impaired foetal growth--nutritional causes and treatment.

PMID- 10944871
TI  - Colour vision defects among doctors and diabetic patients: implications for
      diagnosis and management.

PMID- 10944872
TI  - Treating a hidden problem: tuberculosis among China's 'floating people'.

PMID- 10944873
TI  - Cancer patients are now surviving longer in Britain.

PMID- 10944874
TI  - Carcinoid tumours--the carcinoid syndrome and serotonin (5-HT): a brief review.

PMID- 10944875
TI  - Serotonin (5-HT) and neuropsychiatric disorders.

PMID- 10944876
TI  - Food hygiene--a critical examination of standards.

PMID- 10944877
TI  - Escherichia coli--a review.

PMID- 10944878
TI  - Tomatoes and health.

PMID- 10944879
TI  - Aircraft cabin environment.

PMID- 10944880
TI  - Liquorice and its health implications.
AB  - This article presents an overview of the health implications of liquorice.
      Liquorice has beneficial applications in the medicinal and the confectionery
      sectors; the substance, therefore, is both widely available and commercially
      attractive. However, the ingestion of liquorice, and/or its active metabolites,
      can sometimes produce an acquired form of apparent mineralocorticoid excess (AME)
      syndrome, expressed as sodium retention, potassium loss and suppression of the
      renin-angiotensin-aldosterone system, in addition to clinical consequences such
      as raised blood pressure and oedema. Moreover, these metabolic changes, the
      mechanisms underlying which are highlighted in the accompanying text, are
      associated with a number of additional clinical symptoms. Considering the easy
      availability of liquorice itself and also of other products containing its active
      metabolites, it is quite possible that the health burden of liquorice-induced
      morbidity could be substantial. Healthcare practitioners need to be fully aware
      of the risks in view of a large number of reports in the literature concerning
      its toxicity.

PMID- 10944881
TI  - 'Glue ear' in perspective.
AB  - Contrary to common perception 'glue ear' is a vast and complex subject. It is the
      most common cause of hearing loss in children; its treatment is often questioned
      and involves utilisation of substantial health service resources. This article is
      aimed not only at placing the condition in perspective but also at establishing a
      short yet comprehensive understanding of its many aspects including aetiology and
      management. There is no intention, however, to dwell here excessively upon its
      intricacies and abstrusities.

PMID- 10944882
TI  - Health information on the Web: pregnancy.
AB  - The internet and computers have already become an important part of the daily
      lives of many. Through the touch of a button we can now obtain almost any
      information we desire without even leaving our homes. Although pregnancy is a
      common physiological event, anxiety is one of its frequent accompaniments and the
      anxiety may be of a high degree. Every woman desires to know in great detail
      about her own pregnancy. Even though the web is so easily accessible it is,
      nevertheless helpful to know which websites to surf in order to avoid wasting
      valuable time. The following list is a compilation of such sites, all of which
      have been tested and proved to be both valuable and informative; they should,
      moreover, provide interesting reading.

PMID- 10944883
TI  - A survey of postgraduate education programmes and research interests of GPs in
      community trusts in an inner city area.
AB  - Following discussions with medical lecturers in a postgraduate centre, a
      questionnaire was sent to all the general practitioners (GPs) in three selected
      Community Trusts in an inner city area. Besides their qualifications and research
      interests, the GPs were asked for their views on continuing education. The
      results showed that opportunities for collaborative education with other members
      of the primary care groups (PCGs) would be possible if it focused on research
      methods and 'Health of the Nation' targets. The results showed that up to 61% of
      the GPs who responded had carried out research and had collaborated with nurses
      on the research projects. There was considerable variation across the Community
      Trusts in relation to the experience and interests of the GPs. The formation of
      the PCGs and joint commissioning offered an excellent opportunity for both
      collaborative educational opportunities and research. As the interests of the GPs
      is so diverse, some thought about consolidating and harnessing their interests
      and expertise in order to influence local and national research agendas may be of
      value.

PMID- 10944884
TI  - Comparison of anthropometric characteristics between normotensive and
      hypertensive individuals among a population of Bengalee Hindu elderly men in
      Calcutta, India.
AB  - A comparative investigation of 99 normotensive and 111 hypertensive Bengalee
      Hindu elderly men (aged 55 years and above) of Kalighat, South Calcutta, India,
      was undertaken to study differences in levels of adiposity, body fat distribution
      and body composition between these two groups. Results revealed that there were
      significant differences between normotensive (NT) and hypertensive (HT) subjects
      in the mean values for weight (p < 0.05), body mass index (BMI, p < 0.01); waist
      (p < 0.001) and hip circumferences (p < 0.05); waist-hip ratio (WHR, p < 0.001),
      conicity index (CI, p < 0.01) and fat free mass (FFM, p < 0.001). Percentile
      distributions for all these variables and indices showed consistently higher
      values among the HT patients as compared with NT subjects. However, the frequency
      of obesity (BMI > or = 25) was similar (NT = 6.1%, HT = 11.7%) in both groups.
      Thus, these results indicated that there existed significant differences in
      central adiposity and FFM between NT and HT subjects although their level of
      obesity was similar. Hypertensive individuals have significantly enhanced levels
      of central body fat distribution.

PMID- 10944885
TI  - The long-term safety and tolerability of ispaghula husk.
AB  - The safety and tolerability of ispaghula husk, which can now be used as an
      adjunct to diet for the treatment of mild-to-moderate hypercholesterolaemia, was
      assessed in 93 healthy subjects over a 52-week period. The study looked at the
      nutritional, biochemical, and haematological effects of ispaghula. Over the study
      period there were small but statistically significant changes in some
      measurements of minerals and vitamin levels, and in some haematological and
      biochemical parameters. However, none of these were of clinical significance,
      with the possible exception of changes in vitamin B12 levels. A daily dose of
      10.5 g ispaghula was well tolerated and the majority of adverse events recorded
      were minor, of short duration and either unrelated or possibly related to the
      study treatment. The results suggest that ispaghula husk can be used with
      confidence for the long-term treatment of mild-to-moderate hypercholesterolaemia.

PMID- 10944886
TI  - A rapid appraisal method for the selection and pre-testing of environmental
      health leaflets.
AB  - This paper presents a rapid appraisal method for the selection and pre-testing of
      printed leaflets on environmental health issues. The method combines a staff
      questionnaire, a readability test and a target population survey and is designed
      to aid leaflet selection in a way which is practically feasible yet retaining an
      acceptable level of face validity. A multiple, embedded case study was used to
      field-test the method and the feedback from this is discussed. The results
      suggest that the method has the potential to replace ad hoc arrangements by the
      gatekeepers and make the selection of leaflets more a matter of structured
      decision-making involving representatives of all the stake-holders.

PMID- 10944887
TI  - Micronutrient intakes in a group of UK vegans and the contribution of self
      selected dietary supplements.
AB  - Micronutrient intakes and the contribution of self-selected dietary supplements
      were investigated in 26 vegans, comprising 17 non-supplement users (NSU) and nine
      supplement users (SU), consuming their habitual diet. Micronutrient intakes were
      estimated using a four-day weighed record and the contribution of self-selected
      dietary supplements was assessed according to the manufacturers' declarations on
      the packaging. Mean daily intakes from food sources were similar in NSU and SU.
      Dietary supplements significantly increased intakes of riboflavin (p < 0.05),
      niacin (p < 0.05), folate (p < 0.01), vitamin A (p < 0.05) and vitamin D (p <
      0.05). The mean daily contribution of dietary supplements ranged from 7-1640% of
      the reference nutrient intake (RNI). Intakes of vitamin B12 and selenium (Se)
      were below the appropriate lower reference nutrient intake (LRNI) in 80% and 65%
      of NSU respectively. After supplements, 33% of SU remained below the LRNI for
      vitamin B12 and 33% below the LRNI for Se. Some vegans who took supplements were
      not taking certain micronutrients in amounts sufficient to meet the RNIs but were
      taking a mix of micronutrients, some of which they needed and others which they
      did not need. Some vegans who did not take supplements had a potential need for
      the addition of supplements to their diets. Advice on the appropriate usage of
      dietary supplements for those on a vegan diet is needed.

PMID- 10944888
TI  - Historical perspectives on health: Johann Friedrich Meckel the younger and his
      diverticulum.

PMID- 10944889
TI  - Lessons to be learned: a case study approach. Unseasonal severe poisoning of two
      adults by deadly nightside (Atropa belladonna).
AB  - Unseasonal, mid-winter, severe poisoning by deadly nightshade is reported in two
      adults who simultaneously ate from a pie made of frozen deadly nightshade
      berries, mistaken at the time of picking for bilberries. Atropine levels are
      reported in the urine. Physostigmine treatment was ineffective.

PMID- 10944890
TI  - [Optimal conditions for establishment of experimental tuberculosis model using an
      automated inhalation exposure apparatus and its application].
AB  - Animal (mouse and guinea pig) pulmonary tuberculosis models were established,
      using an automated inhalation exposure apparatus (Glas-Col Corp., USA, Model
      099CA-4212). This apparatus includes four steps--preheating, nebulization, cloud
      decay and decontamination. The optimal conditions for M. tuberculosis H37Rv
      strain infection experiments were as follows: 10(5-6) colony forming unit (cfu)
      tubercle bacilli; preheating for 15 min.; nebulization for 90 min.; cloud decay
      for 15 min. and decontamination for 5 min. When 10(4) cfu M. tuberculosis H37Rv
      strain were introduced into the lungs of interferon (IFN)-gamma knockout mice,
      using the inhalation exposure apparatus and were followed up for 9 months, the
      primitive cavitary lesions were observed. This apparatus was also useful for
      inhalation exposure experiments of guinea pigs. This apparatus can also be
      utilized for animal inhalation experiments of allergens.

PMID- 10944891
TI  - [A study on the effect of combined chemotherapy on Mycobacterium avium complex
      pulmonary disease].
AB  - Annual incidence of Mycobacterium avium complex (MAC) pulmonary disease has been
      gradually increasing in the last 10 years in Japan, however, the optimal
      therapeutic regimen for the disease has not yet established. We investigated the
      effect of our new regimen in twenty seven cases of pulmonary MAC infection
      without HIV infection, diagnosed according to the American Thoracic Society
      criteria during the period from January 1996 to October 1997 at our hospital.
      These patients were treated with rifampicin (RFP), ethambutol (EB) and
      clarithromycin (CAM) for more than 12 months, together with streptomycin (SM)
      initially (first 2-3 months), except one patient who was treated for 11 months
      only. Twenty-four months after the therapy, sputum cultures converted from
      positive to negative in 13 patients and the amount of bacilli in sputum reduced
      in two patients. The radiological findings improved in 10 patients, showed no
      significant changes in 11 patients, while worsened in the remaining 6 patients.
      As to adverse reactions 1 case of liver damage, 3 cases of skin disorders, 4
      cases of gastrointestinal malfunctions, and 1 case of optic neuritis were
      observed. This regimen was safe and tolerable even in the elderly outpatients,
      but not so effective against MAC pulmonary disease compared with the results of
      recent reports from the U.S. and Europe. Size of pulmonary lesions was closely
      associated with the effectiveness in this study. However, five bacteriologically
      converted cases did not show radiological improvement, and the reasons behind
      this fact remain to be investigated.

PMID- 10944892
TI  - [Changes in antibacterial activity of murine peritoneal macrophages against
      Mycobacterium tuberculosis after prolonged in vitro precultivation].
AB  - We examined profiles of intramacrophagial growth of M. tuberculosis (MTB) when
      mouse peritoneal macrophages (M phi s) were infected with the organisms at day 0
      or day 7 after in vitro precultivation, and obtained the following results.
      First, the growth rate of the virulent MTB H37Rv strain as well as attenuated
      H37Ra strain was slower in M phi s which had been precultured for 7 days (M phi s
      [day 7]) than in freshly prepared M phi s without precultivation (M phi s [day
      0]). The doubling time of MTB H37Rv was 2.2 and 2.9 days in M phi s [day 0] and M
      phi s [day 7], respectively, and that of MTB H37Ra was 2.9 and 3.6 days in M phi
      s [day 0] and M phi s [day 7], respectively. Second, MTB-mediated cytotoxicity in
      terms of the LDH release from infected M phi s was less marked in M phi s [day 7]
      than in M phi s [day 0], when they were infected with MTB of either the H37Rv or
      H37Ra strain. MTB H37Ra strain exhibited much weaker cytotoxic effects on host M
      phi s than did H37Rv strain. Third, when M phi s [day 7] were infected with MTB
      of either the H37Rv or H37Ra strain, they showed markedly lowered levels of
      reactive oxygen intermediate (ROI) production than did M phi s [day 0]. In
      contrast, the reactive nitrogen intermediate (RNI) producing ability of M phi s
      in response to MTB infection was not so markedly reduced in M phi s [day 7] from
      that of M phi s [day 0]. As mentioned above, the M phi s [day 7] did not permit
      accelerated growth of infected MTB, compared to the MTB growth in the M phi s
      [day 0]. It thus appears that ROI played a trivial role in the antimicrobial
      activity against MTB of murine peritoneal M phi s which had been precultured for
      long periods. Although it is regarded that RNI played more critical roles in M
      phi anti-MTB activity than did ROI, the present results also suggest that other
      kinds of antimicrobial effectors are required in M phi antimicrobial activity
      against MTB organisms, particularly in the case of M phi s after prolonged in
      vitro cultivation.

PMID- 10944893
TI  - [Fifty years of research on tuberculosis. Lessons I have learnt during 50 years
      and topics to be investigated in the future].
AB  - I have engaged in the research on tuberculosis for 50 years, and lessons I have
      learnt during this period could be summarized in the following ten topics. First
      is great research achievements by our predecessors on the establishment of so
      called primary infection theory on the pathogenesis of TB, planning of TB control
      principles based on the theory and development of new technologies used for TB
      control, such as mass miniature X-ray examination and BCG vaccination in 1920s
      and 1930s. TB control law was enforced in 1951, and the modern TB programme was
      initiated. Second, the field is a treasure house of interesting data. Several
      interesting data on TB soon after the World War II in Tokyo and a rural area were
      collected and analyzed from the mass health examination. Third, looking at the
      increase of tuberculin positivity with age, it was found that the tuberculin
      negativity decreased as the exponential function of age, and the current concept
      of the annual risk of TB infection was already developed in late 1940s. It was
      18.1% in male and 11.6% in female in Tokyo in late 1940s. Based on this concept,
      age specific TB mortality was analyzed by the type of TB, and the rates of
      miliary TB and TB meningitis were similar to the rate of newly infected to the
      total population, while the rate of all forms could be divided into early and
      late death as shown in Fig. 1. Fourth, I suffered from TB by myself from 1951 to
      1953, receiving first thoracoplasty in two stages under local anaesthesia, then
      right upper lobectomy and segmentectomy of superior segment of right lower lobe.
      From this experience, I learnt a lot about the psychology and suffering of TB
      patients. Fifth, the importance of recognition of real magnitude of the problem
      in such a disease as TB in which many TB cases did not aware of their disease.
      The answer to this was the first TB prevalence survey in 1953 using stratified
      random sampling method, and based on the results of the survey, the mass health
      examination originally focussed on youth was expanded to the total adult
      population of Japan. Sixth, TB could be reduced rapidly by applying appropriately
      planned control programme. In big enterprises, the application of intensive case
      finding programme brought about the rapid decline of severe TB cases, contributed
      to the increase of the productivity of the enterprises, thus to the rapid
      increase of GDP of whole Japan, and the growing spiral between the improvement of
      health and the economic development was formed by successful TB control. In
      addition to the mass health examination, BCG vaccination and spread of
      appropriate treatment in the original TB control law, the registration and case
      management system and the more extensive application of hospitalization for
      infectious cases were introduced in early 1960s. Observing the proportion of TB
      care expenditure to the national medical expenditure, it was 28% in 1954, and it
      dropped down to 0.4% in recently as shown in Fig. 2. The decline of TB in Japan
      during 1950s and 1960s was one of fastest in the world. Seventh, there had been
      marked differences in the prevalence of TB as well as the coverage and quality of
      TB programmes in several areas of Japan though it was often said that Japan is
      homogeneous country. To know the real status in various areas of Japan, a chart
      to express graphically the magnitude of TB and coverage and quality of TB
      programmes was developed (Fig. 3), and it was finally refined to the current
      form. Eighth difficulty in changing existing programmes, and we are grateful for
      kind cooperation of Niigata Prefecture for making several new attempts. Ninth, it
      has been needed to observe TB problems from global standpoint, and it was
      actually done through participation to the bilateral cooperation projects on TB
      control and conducting the international training courses sponsored by JICA.
      Tenth, TB is a pertinacious disease. As shown in Fig. (ABSTRACT TRUNCATED)

PMID- 10944915
TI  - [Sleep apnea syndrome and its mortality].
AB  - The definition and the outline of historical background of sleep apnea syndrome
      (SAS) was given. The clinical issues related to daytime hypersomnolence and
      morbid obesity in SAS patients were also focused from the viewpoints of their
      cardiovascular complications and mortality. The difference of SAS was also
      compared and discussed between Caucasian and Japanese.

PMID- 10944916
TI  - [Epidemiology of sleep apnea syndrome].
AB  - Recent epidemiological studies found an extraordinarily high prevalence of sleep
      disordered breathing(SDB) in an apparently healthy population in the USA,
      Australia and Italy. Estimated prevalence for apnea-hypopnea index > or = 5 and >
      or = 10 were 24-78% and 15-35% for men and 9-55% and 5-20% for women in middle
      aged populations. Obesity and craniofacial dysmorphism are two major risk factors
      to SDB. Apparent racial differences in the prevalence of SDB were found in the
      USA population and the differences could be explained with racial characteristics
      in craniofacial features. The lower limit of the prevalence of SDB was estimated
      with 0.5-2.9% in child populations in North Europe. Clinical significance of SDB
      in children should be carefully evaluated near future.

PMID- 10944917
TI  - [The relationship between adhesion molecules and hypoxia].
AB  - Hypoxia is an essential developmental and physiological stimulus that plays a key
      role in the pathophysiology of heart attack, cancer and other major causes of
      mortality. Recently studies have shown that hypoxia itself may directly activate
      NFk-B. NFk-B sites are also present in the promoter of the ICAM-1 gene.
      Therefore, it is possible that hypoxia could directly activate the ICAM-1,
      through activation of NFk-B. Hypoxia-inducible factor 1 is the only known
      mammalian transcription factor expressed uniquely in response to physiologically
      relevant levels of hypoxia. In the another cause of the induction of adhesion
      molecules with hypoxia adhesion molecules are induced by the inflammatory
      cytokine(IL-1, TNF alpha) that caused with anoxia/reperfusion. The adhesion
      molecules induced by hypoxia play one of the key rolls of the various diseases.
      For example the level of cICAM-1 in OSAS patients were increased. These
      observations suggest that OSAS-induced hypoxia activate adhesion molecules,
      resulting in the important risk factor of cardiovascular disorders.

PMID- 10944918
TI  - [The role of superoxide in relationship between the cardiovascular diseases and
      the metabolic disorders associated with obesity].
AB  - Both cardiovascular diseases such as hypertension and atherosclerosis and
      metabolic disorders such as diabetes mellitus and hyperlipidemia are closely
      related with obesity. In recent studies, superoxide is supposed to play an
      important role in pathogenesis of the cardiovascular diseases. Superoxide
      inhibits the biological action of nitric oxide, known as endothelium-derived
      relaxing factor, leading to vasoconstriction. Moreover, superoxide directly
      affects the functions of endothelial cells and vascular smooth muscle cells. It
      has been investigated that the metabolic disorders associated with obesity
      enhance the superoxide production in the arterial walls through the insulin
      resistance. In hyperglycemic state, the production of superoxide is stimulated
      and the superoxide dimustase is inhibited by non-enzymatic glycation, known as
      Maillard reaction. Hyperlipidemia also increases endothelial superoxide
      production. Superoxide may act a key role in relationship between the
      cardiovascular diseases and the metabolic disorders associated with obesity.

PMID- 10944919
TI  - [Autonomic function and circulatory failure].
AB  - To define fundamental mechanisms for sympathoexcitation could provide a
      therapeutic opportunity to interrupt the specific site linking sympathetic
      activation with heart failure. Central sleep apnea is characterized by apnea,
      hypoxia, sleep fragmentation, and increased sympathetic nerve activity. Since
      this sympathoexcitation is directly related to the frequency of arousals from
      sleep and the degree of apnea-related hypoxia, but not to left ventricular
      ejection fraction, it is therefore not simply a compensatory response to
      hemodynamic derangement but is excessive and pathologic sympathoexcitation with
      aftereffects that persist into wakefulness. Thus, central sleep apnea could
      participate in a vicious pathophysiologic cycle involving the cardiovascular,
      respiratory, and autonomic nervous system.

PMID- 10944920
TI  - [Microgravity and autonomic nervous system].
AB  - How microgravity influences autonomic function is still under investigation.
      Microgravity induces neuro-vestibular alterations and body fluid shift, and these
      two changes cause "space motion sickness(SMS)" and cardiovascular deconditioning.
      "Space motion sickness" is a autonomic syndrome that exhibits nausea, vomiting,
      headache, anorexia, pallor etc., whose incidence in Space Shuttle mission reaches
      67.1%. There are several hypotheses for SMS mechanism: 1) sensory conflict, 2)
      fluid shift, 3) otolith asymmetry, 4) space orientation readaptation, 5) otolith
      tilt-translation reinterpretation, and these hypotheses are considered to be
      combined together to cause SMS. After space flight, 64% of the astronauts suffer
      from orthostatic intolerance, which is defined as incompletion of 15 min of 70
      degrees head-up tilt. Several causes for the deconditioning have been
      hypothesized, dehydration followed by fluid shift, altered gain for baroreflex
      sensitivity, decreased venous capacitance, etc. In our previous studies, we
      recorded muscle sympathetic nerve activity(MSNA) by microneurography under
      simulated and actual microgravity conditions. Parabolic flight, which induces 20
      sec of actual microgravity, suppressed MSNA to 50%. Head-out water immersion
      suppressed MSNA to 20% while gradual recovery was observed during 3 hours of
      immersion. Dry immersion for 3 days revealed that MSNA was enhanced after
      simulated microgravity while the response to orthostasis was unchanged. Bed rest
      for 6, 14, and 120 days and Neurolab Project clarified the same tendency for
      longer duration of simulated microgravity. These alterations in MSNA might be
      attributed to the development of cardiovascular deconditioning after microgravity
      exposure.

PMID- 10944921
TI  - [Hypoxemia and tissue hypoxia in sleep apnea syndrome].
AB  - Hypoxemia is defined as abnormally reduced oxygenation of the blood, whereas
      tissue hypoxia indicates inadequate oxygen supply against oxygen demand in the
      integrity of cellular metabolic processes. Thus, the presence of tissue hypoxia
      may not be predicted by the level of hypoxemia alone. Obstructive sleep apnea
      syndrome is characterized by periodic apnea/hypopnea, which is often associated
      with severe hypoxemia. In this chapter, we discussed how tissue hypoxia should be
      assessed in this syndrome, and also what is the clinical usefulness and/or
      limitations of such assessment.

PMID- 10944922
TI  - [Pulmonary hypertension].
AB  - Repetitive pulmonary artery pressure(PAP) elevation during apnea is commonly
      reported in patients with obstructive sleep apnea syndrome(OSAS). Hypoxic
      pulmonary vasoconstriction(HPV) plays an important role in this PAP elevation. In
      addition to the HPV, augmentation of intrathoracic negative pressure which occurs
      concomitantly with apnea and activation of sympathetic nervous system during REM
      sleep, influences pulmonary blood flow, resulting in the PAP elevation. Many
      previous study have been declared that the daytime pulmonary hypertension(PH),
      which is observed in significant populations of OSAS, is related to chronic
      airflow limitation and/or daytime hypoxemia. Furthermore, it had been suggested
      that the daytime PH in OSAS can be elicited, at least in parts, by vascular
      remodeling together with both nocturnal and daytime hypoxemia. Such pulmonary
      vascular remodeling may induce greater vascular sensitivity to sympathetic
      stimulation and modify HPV in OSAS with daytime PH.

PMID- 10944923
TI  - [Endocrine disturbances in sleep apnea syndrome].
AB  - Sleep apnea may interact endocrine rhythms by a number of mechanisms. Repetitive
      apneas will cause sleep fragmentation and disorganization of sleep stages and
      cycles. How this compares with hormonal changes secondary to sleep deprivation is
      unclear. Hypoxia may have direct central effects on neurotransmitters, which in
      turn will affect hypothalamic-pituitary hormone production. And, sudden arousal
      from sleep may produce a central stress response leading to hormonal changes.
      These factors may interact and lead to changes in the central of sleep and
      endocrine rhythms. We describe Growth hormone and Androgens secretion during
      sleep with obstructive sleep apnea patients.

PMID- 10944924
TI  - [Abnormality of blood congulation].
AB  - Obstructive Sleep Apnea(OSA) is associated with an increased prevalence of
      cardiovascular complication such as systemic hypertension, ischemic heart disease
      and stroke, which may lead to unexpected or early death. Sleep in patients with
      OSA demonstrates a pattern of recurrent arousals, hemodynamic changes, and
      sympathetic neural activity that have been associated with adverse carviovascular
      events following awakening in the morning. Neurologic problems in patients with
      OSA include cognitive impairment, poor memory, and high risk for cerebral
      infarction. These central nervous system symptoms might be due to hypoxemia and
      sleep fragmentations. The vascular endothelial damage, platelet aggregation, and
      hemodynamic changes during sleep apnea are influenced by changes in oxygen and
      carbon dioxide tension inducing alterations of vascular tone. The cerebral
      hemodynamics in relation to apneas may not only influence daytime cerebral
      symptoms but may also have implications for the generation of cerebrovascular
      disease in OSA. These changes resulted from OSA might play an important role in
      pathophysiological aspects of the central nervous system. And these changes will
      be improved after CPAP application.

PMID- 10944925
TI  - [Leptin and stress protein (heat shock protein 72: HSP72) in patients with
      obstructive sleep apnea-hypopnea syndrome].
AB  - Leptin is a circulating hormone that is expressed abundantly and specifically in
      adipose tissue. Leptin induces a complex response involving control of body
      weight, energy expenditure and fat distribution. It is difficult for patients
      with obstructive sleep apnea-hypopnea syndrome to reduce and maintain their
      weights. Therefore, it is important to understand the circadian rhythms and
      regulation of serum leptin levels in order to control the body weight of
      obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. Heat shock
      protein(HSP) 72 is generally known to be a stress-inducible isoform that is
      barely detectable under unstressed conditions but which is rapidly synthesized
      during or after stress. Recent data suggest that OSAHS may have significant
      effects on the serum leptin levels and HSP72 levels in peripheral blood
      mononuclear cells(PBMC) of patients with OSAHS.

PMID- 10944926
TI  - [Polysomnography].
AB  - Polysomnography(PSG) is essential for the diagnosis of all pathophysiologic
      conditions due to both any types of sleep disordered breathing and to any types
      of sleep disturbance. Since this issue's objection is to describe the outline of
      PSG, we will explain here about when PSG is needed, what type of measurements are
      necessary for PSG, and how it should be interpreted from the result of the PSG
      tracing for the diagnosis for sleep apnea syndrome, etc.

PMID- 10944927
TI  - [Automatic analysis of sleep EEG].
AB  - Since a manual of standardized scoring system for sleep stage was reported by
      APSS, the sleep researches remarkable advanced. But it took sleep researchers
      many times and effort to analysis of numerous data. The digital and computer
      technique were advanced about 10 years, so that, paper polysomnography(PSG) has
      been replaced with computerized polysomnography(PSG). The computerized PSG is
      useful for sleep stage scoring and storage of data. It is pointed out that the
      correctness of computerized analysis unfortunately is less than visual.
      Generally, computerized analysis is performed to apply the manual of APSS. This
      manual is not able to computerized analysis. Because this manual was developed
      for visual. In 1999, Japanese sleep research society was reported a manual of
      sleep stage scoring for computerized analysis which was modified the manual of
      APSS. It is expected to development of computerized PSG system which is able to
      yield the result similar to that obtained with visual.

PMID- 10944928
TI  - [Acoustic reflection technique].
AB  - Acoustic reflection technique has been employed to assess the pharyngeal cross
      sectional area in sleep apnea patients. It has the advantage of being noninvasive
      and quick, and it also allows for continuous evaluation of the patency of these
      regions. The technique, however, has never been used during sleep because of its
      restrictions. This issue overlook the recent progress of the technique, i.e., the
      newly developed nasal acoustic reflection technique which enabled us to assess
      the pharyngeal cross-sectional area during sleep. Application of this technique
      includes a method of determining the site of pharyngeal occlusion, a method of
      evaluating the efficiency of various therapeutic methods of sleep apnea, and a
      method of measuring the upper airway collapsibility during sleep.

PMID- 10944929
TI  - [Multiple sleep latency test].
AB  - Daytime sleepiness is such a familiar thing for most Japanese, dozing off in a
      commuting train is regarded as completely normal. Sleepiness, however, can yield
      a lot of problems. Not only deteriorating efficiency of the work, it sometimes
      leads to traffic accidents, and also serves as a cause for disastrous accidents.
      Although excessive daytime sleepiness has been gradually known to Japanese health
      workers as one of the symptoms of sleep apnea syndrome, some patients cannot
      recognize sleepiness, and even neglect it, feeling others are sleepy as well. In
      this respect multiple sleep latency test is a valuable tool as an objective
      measures of daytime sleepiness, and commonly used procedures of this testing was
      described in details.

PMID- 10944930
TI  - [Diagnosis of sites of upper airway obstruction in patients with obstructive
      sleep apnea].
AB  - Precise determination of the site of obstruction is mandatory for improvement of
      surgical outcome. The size of the upper airway depends on the balance between the
      upper airway(UA) muscle activity and intraluminal pressure. Structural property
      of the UA is considered to be a fulcrum of the balance model. Our final goal is
      to identify structural abnormalities within the UA. State-dependent and
      individual variability of the UA muscle activity and luminal pressure makes
      interpretation of UA size difficult. Measurements of UA size and evaluation of UA
      collapsibility may be less valuable during wakefulness and sleep without
      controlling the variability. Two unique approaches to identify the anatomic
      abnormalities while controlling the UA muscle activity and luminal pressure were
      reviewed.

PMID- 10944931
TI  - [Exhaled nitric oxide].
AB  - We introduce the standard method of measurement of nitric oxide recommended by
      American thoracic society in 1999 and report the results of exhaled NO and nasal
      NO in patients with obstructive sleep apnea syndrome(OSAS). Our data showed lower
      exhaled NO output in the patients with OSAS than that of normal volunteers(NV)
      and that of patients with simple obesity(SO). On the other hand, nasal NO in the
      OSAS patients is higher than that of NV and that of SO patients. Also, there were
      significant relationships between apnea index and exhaled NO and between
      desaturation during sleep and nasal NO. These findings suggested that NO from
      lower and upper airway will be a non-invasive maker of sleep disordered breathing
      in future.

PMID- 10944932
TI  - [Drug therapy for sleep apnea syndrome].
AB  - The number of patients suffering from sleep apnea syndrome(SAS) have been
      increased. In recent years, many therapeutic approaches such as nasal CPAP,
      dental appliance, upper airway surgery, pharmacological agents, have been used
      for the treatment of SAS. The various drugs(acetazolamide, some tricyclic
      antidepressant, progesterone, theophylline, aminophylline and so on) have been
      used for pharmacotherapy of SAS. Acetazolamide have been established as the best
      medication. But all approaches without acetazolamide, could not shown their
      satisfactory effects on SAS. In this article, drug therapy for SAS is described.

PMID- 10944933
TI  - [Nasal continuous positive airway pressure and noninvasive positive ventilation
      in the treatment of sleep apnea/hypopnea syndrome].
AB  - The main medical treatment of moderate to severe obstructive sleep apnea/hypopnea
      syndrome is nasal continuous positive airway pressure(nCPAP). When compliance of
      the patient is low due to nasal or oral dryness, heated humidifier is added to
      nCPAP. In Japan frequent complaints such as nasal cold and dryness were observed
      in winter because of infrequent air conditioning in the sleeping room. In the
      case of dyspnea using nCPAP, bilevel PAP or auto CPAP is recommended. We treated
      384 patients with nCPAP and 24% of the patients were added heated humidifier.
      Auto CPAP and bilevel PAP was administered in 10% and 6% of the patients
      indicated for PAP treatment, respectively.

PMID- 10944935
TI  - [Dental device (sleep splint)].
AB  - Sleep splint, which is a dental device made of regin, is now widely used for the
      treatment of obstructive sleep apnea in our country. This device is worn in the
      mouth at night and makes the upper airway opened during sleep. It enlarges the
      velopharyngeal space as well as the space at the tongue base and prevents the
      collapse of the upper airway. This device is a treatment of choice for the
      patients with mild or moderate types of obstructive sleep apnea who are not
      treated ordinarily by nasal CPAP. When the patients have nasal obstruction,
      adenoid hypertrophy, enlarged tonsils, or improper conditions of the teeth, sleep
      splint is not indicated for those patients. At first, nasal obstruction should be
      treated, and the adenoids and enlarged tonsils should be removed surgically. The
      compliance of this treatment is better than that of nasal CPAP, and the major
      complication of this treatment is almost none.

PMID- 10944934
TI  - [Long-term result after UPPP for OSAS by evaluation of nocturnal oxygenation].
AB  - The nocturnal oxygenation of 45 patients with OSAS who had UPPP at our hospital
      were evaluated by pulse oximetry before and after surgery and at the time more
      than one year after UPPP. "Successful case" is defined as the case that showed
      more than 50% reduced oxygen desaturation index(ODI) after UPPP. Twenty seven
      cases including 15 severe cases(ODI > or = 40) have showed continuously
      successful ODI for more than one year. We could not get good result in 8 cases,
      which kept high ODI. Four of them are now using dental appliance. We have
      recognized the recurrence of sleep apnea in 10 cases that once got successful
      results just after UPPP. Our report strongly suggests the importance of long-term
      follow-up after surgery.

PMID- 10944936
TI  - [Telemedicine and lifestyle modifications in obstructive sleep apnea patients].
AB  - The recent advent of information technology(IT) has led to the application of
      telemedicine to the diagnosis of sleep-disordered breathing(SDB) such as
      obstructive sleep apnea(OSA). Trials with automatic SDB analyzers(Night Watch and
      Alice 4) are investigating the use of home SDB testing via telephone circuits or
      the internet, home continuous positive airway pressure(CPAP) titration via remote
      control, and super-remote polysomnographic monitoring using the time difference
      between Japan and the United States. In 1994, we developed a computer-controlled
      lifestyle improvement support system(AILIFE) using a telephone circuit. The
      support system is expected to heighten the effectiveness of treatments for OSA
      with CPAP, prosthetic mandibular advancement, or uvulopalatopharyngoplasty by
      improving the lifestyle of OSA patients through the provision of home-based
      guidance on nutrition and exercise via telecare.

PMID- 10944937
TI  - [Future direction of therapies for sleep related breathing disorders].
AB  - There are several mechanisms by which pharmacologic agents might improve sleep
      related breathing disorders. Upper airway muscle atony during sleep and fat
      deposition on the upper airway walls are critical in the pathogenesis of upper
      airway obstruction. As central neuromediators that regulate upper airway muscle
      activity, serotonin, gamma amino-butyric acid and thyrotropin releasing hormone
      are reviewed. Although agonists or antagonists of these mediators changed the
      upper airway muscle activity, no agents have successfully improved sleep related
      breathing disorders. Leptin is a protein produced by adipose tissue that
      interacts with receptors in the hypothalamus to inhibit eating. Leptin might have
      therapeutic potential for obesity-related breathing disorders related to a
      relative deficiency in leptin, or a leptin resistance.

PMID- 10944938
TI  - [Snoring and upper airway resistance syndrome].
AB  - Snoring is an inspiratory noise caused by vibration of soft palate and posterior
      faucial pillars. Snoring corresponds to partial obstruction of upper airway, and
      complete obstruction is followed by an apnea. Heavy snoring is practically always
      present in obstructive sleep apnea syndrome. Upper airway resistance syndrome
      (UARS) was first used by Guilleminault and colleagues to describe a subgroup of
      patients with conditions that were formerly diagnosed as idiopathic hypersomnia
      or CNS hypersomnia. These terms used to describe excessive daytime sleepiness
      without a cause that was clearly defined by a nocturnal polysomnogram or the
      multiple sleep latency test. The clinical importance of snoring and UARS is
      reviewed in this article.

PMID- 10944939
TI  - [Sleep apnea syndrome (SAS) and ischemic heart disease (IHD)].
AB  - Several epidemiological studies have suggested that sleep-disordered breathing is
      a risk factor for cardiovascular disease, particularly hypertension, stroke and
      IHD. The relative risk for IHD among obstructive SAS(OSAS) patients is 1.2 to 6.9
      higher compared with the general population. The prevalence of SAS with an apnea
      hypopnea index(AHI) of 10 and over was 35 to 40% in IHD, while 23.8% of SAS
      patients had IHD. These evidence suggests that IHD is an important prognostic
      factor in SAS patients. Characteristic pathophysiological conditions such as
      sleep apnea-induced hypoxemia and sympathetic activation may play an important
      role in the genesis of nocturnal angina pectoris. Most patients with OSAS are
      obese, and the complication of non-insulin dependent diabetes mellitus is quite a
      few. Insulin resistance is also attracting great attention as a cause of the
      cardiovascular complication of SAS.

PMID- 10944940
TI  - [Diabetes mellitus and sleep apnea syndrome].
AB  - Epidemiologic evidences suggest that obstructive sleep apnea syndrome(OSAS)
      itself induces risk factors for cardiovascular diseases(= insulin resistance)
      independent of obesity. Our data suggest that moderate to severe OSA(AHI = > 20)
      is a contributing factor to the development of hyperinsulinemia, abnormal glucose
      metabolism and non-insulin-dependent diabetes mellitus(NIDDM) independent of
      aging, obesity and hereditary predisposition for DM in patients with OSAS. On the
      other hand, disagreement exists as to the incidence of OSAS in DM patients. Some
      authors reported that the incidence of OSAS was high among patients with DM,
      while others did not find such relationship. In these studies, the number of
      cases studied was small and, in addition, the selection of patients may have been
      biased. Future clinical research is needed to answer this issue.

PMID- 10944941
TI  - [Hypertension and altered cardiovascular variability associated with obstructive
      sleep apnea].
AB  - In the past 5 years several epidemiologic studies have demonstrated that sleep
      related breathing disorders are an independent risk factor for hypertension,
      probably resulting from a combination of repetitive episodes of hypoxia,
      hypercapnea, arousals, and a striking surge in sympathetic excitation, and
      altered baroreflex control during sleep. Obstructive sleep apnea (OSA) may lead
      to the cardiac arrhythmias and myocardial ischemia and it is a possible risk
      factor for stroke. We confirmed that nasal CPAP has been shown to lower blood
      pressure in some hypertensive OSA patients. Early recognition and treatment of
      sleep-apnea may improve cardiovascular function.

PMID- 10944942
TI  - [Obesity and obesity hypoventilation syndrome].
AB  - Some patients with obesity show chronic hypercapnia while awake. Such patients
      are referred to as obesity hypoventilation syndrome(OHS). Particularly, patients
      with profound obesity who have clinical features of sleep disordered breathing,
      hypersomnolence, cor pulmonale and so on represent the Pickwickian syndrome. The
      mechanisms of hypoventilation in OHS are multifactorial. The level of the blunted
      chemosensitivity, mechanical impairments of the respiratory system, the severity
      of the sleep-disordered breathing, and chronic hypoxemia may be important
      determinants of chronic hypoventilation. In this paper, the characteristics of
      pulmonary functions in obesity and the possible mechanisms of hypoventilation in
      patients with OHS were reviewed. Furthermore, the definition of OHS and
      descriptions of thr severity of OHS as recommended by Respiratory Failure
      Research Committee of Japanese Ministry of Health and Welfare are introduced.

PMID- 10944943
TI  - [Sleep apnea in multiple system atrophy].
AB  - Multiple system atrophy(MSA) characterized clinically by any combination of
      autonomic, extrapyramidal or cerebellar symptoms and signs. MSA patients
      frequently manifest a variety of sleep-related respiratory disturbances, which
      are life threatening problems. Above all, a common and serious complication is
      upper-airway obstructive sleep apnea associated with stridor, which is caused by
      vocal cord abductor paralysis(VCAP). For the early diagnosis of VCAP, it is
      important to perform laryngoscopy during sleep, because VCAP does not appear
      during awakefulness in the early stage of MSA. Polysomnographic study should be
      obtain to assess the severity of respiratory disturbances. Tracheostomy is
      reliable treatment for respiratory disturbances due to VCAP, while nasal
      continuous positive pressure may be a useful treatment for some patients.

PMID- 10944944
TI  - [Overview of sleep medicine and sleep respiratory disorders centers in Japan].
AB  - Sleep medicine in Japan evolved gradually, beginning with sleep research being
      conducted in the late 1960's exclusively on the university basis. Japan Sleep
      Society was founded in 1977 mainly by psychiatrists. Recently public awareness
      regarding sleep related breathing disorders has been raised as a result of a
      media campaign in Japan. However, the medical service system is unable to
      appropriately meet the needs of caring for sleep-disordered patients due to
      insufficient reimbursement and the lack of well-trained technical personnel. So
      far only several sleep centers existed in Japan. To make sleep be included in the
      mainstream of the health care system, the educational system and throughout
      society, many tasks remains to be done by healthcare professionals and
      government.

PMID- 10944945
TI  - [Sleep medicine in USA and European countries--now and then].
AB  - In looking to the future in a field such as sleep medicine, there seems to be two
      general areas: (1) the scientific accomplishments that are likely to transpire in
      the years ahead and (2) how sleep medicine will be practiced in our evolving
      medical system. As the care of apnea patients becomes more standardized and
      effective, sleep medicine must be expanded scientifically and clinically, thereby
      becoming a complete and mature field. Advancing basic science and technology is
      likely to improve the well-being of patients with sleep disorders.

PMID- 10944946
TI  - [Endocrinology].

PMID- 10944947
TI  - [Recent studies on anti-angiogenesis in cancer therapy].
AB  - Angiogenesis is known to be a critical process for the tumor growth and
      metastasis. There are many indigenous role-players in tumor angiogenesis and anti
      angiogenesis, where tumor-host interaction may work. A lot of agents with anti
      angiogenic activity have been developed for anti-cancer treatment. Several agents
      including Marimastat, Primostat, Neovastat, Bay-12-9566m, Interferon-alpha,
      SU101, retinoids, and IM862, are/were under phase-three study. There are still
      many future-promising results of basic or clinical studies on inhibitors of MMPs,
      and inhibitors of VEGF/R, Endostatin, somatostatin analogues, COX-2 inhibitors,
      and others. Most of the combination treatments of antiangiogenetic agent and
      conventional anticancer agents therapy, or radiation therapy as we reported,
      showed relatively small or minute increase in toxicity of these cytotoxic
      treatments.

PMID- 10944948
TI  - [Clinical usefulness of intracoronary Doppler for prediction of coronary
      restenosis].
AB  - The Doppler guide wire is widely used in the diagnosis of heart diseases, and in
      particular including ischemic heart disease. It offers various advantages for
      application in tortuous and peripheral arteries, and in the detection of
      functional coronary stenosis that coronary angiography cannot detect. A number of
      multicenter trials have also shown that the Doppler guide wire is of value in
      predicting coronary restenosis after coronary intervention. On the other hand,
      the Doppler guide wire is influenced not only by the stenosis in the epicardial
      coronary artery, but also by stenosis in the vascular beds of coronary
      microcirculation. An appreciation of both the advantages and disadvantages of the
      Doppler guide wire and its usefulness is of considerable importance.

PMID- 10944949
TI  - [Non-specific immunotherapy for the treatment of allergic diseases].
AB  - IgE antibodies play a key role in the development of allergic reactions. Non
      specific immunotherapy which enables to control the IgE dependent response at
      either the synthesis level or the effector phase can be an effective therapeutic
      agent for atopic diseases. To decrease the quantity of IgE anti-IgE molecules
      have been developed. Humanized monoclonal antibodies (mAbs) CGP 51901, CGP 56901
      and rhuMAb E25 are currently under clinical studies. They bind to the C epsilon 3
      domain of human free IgE and surface IgE of IgE expressing B cells but not to IgE
      bound to high affinity IgE receptors (Fc epsilon RI) on mast cells and basofils
      or low affinity IgE receptors (Fc epsilon RII) on other cells, and therefore they
      do not release the histamine and other mediators from these cells. Intravenous
      administration of anti-IgE mAb reduces circulating levels of IgE in atopic
      patients to low levels commonly seen in non-atopic individuals. Anti-IgE therapy
      offers protection against allergen-induced bronchoconstriction and reduces
      severity of symptoms of allergic rhinitis. Anti-IgE mAbs produce improvement in
      lung function and symptom control, they reduce the need for short acting inhaled
      beta 2-agonist and corticosteroids among asthmatic patients. Anti-IgE mAb are
      well tolerated. They do not induce anaphylaxis and the occurrence of antibodies
      against anti-IgE mAb is sporadic. The results of cited studies suggest that
      humanized anti-IgE monoclonal antibodies may have important immunotherapeutic
      benefit for treatment of allergic disorders.

PMID- 10944950
TI  - [Allergy to nickel, chromium and cobalt after osteosynthesis].
AB  - Metals are known as a common cause of contact allergies. The prevalence of
      sensitisation to the composite metals makes for a potential risk of
      osteosynthesis complications in patients suffering from long bones fractures. In
      the study the prevalence of delayed allergy to nickel sulphate, potassium
      dichromate and cobalt was estimated as well as the relation to the osteosynthesis
      complications. The atopy prevalence was estimated too. Persons under examination
      were divided into 3 groups. I--treated with osteosynthesis without complications
      (n = 20), II--treated with osteosynthesis with synostosis complications (n = 16)
      and III--negative controls (n = 34). We estimated 5% prevalence of delayed
      allergy to nickel in group I, 6.25% in group II and 5.8% in group III. In
      patients exposed to chromium we observed delayed allergy prevalence of 5.8% in
      group I and 3% in group III. No allergy to chromium in group II was revealed. No
      allergy to cobalt in all groups was revealed. The prevalence of atopy in group II
      was rare (6.35%) when in group I it was 45% and in controls 32%. The more
      frequent occurrence of type IV allergy to metals in atopic patients was not
      confirmed. There was no difference between the prevalence of delayed allergy to
      metals in groups I and II. Only one case of secondary allergy to chromium was
      observed.

PMID- 10944951
TI  - [Blood serum eotaxin and eosinophil cationic protein in asthmatic patients].
AB  - Eotaxin belongs to CC class of chemokines and is a potent eosinophil
      chamoattractant. Activated eosinophils are able to release many cytotoxic
      proteins, including eosinophil cationic protein (ECP), which has central role in
      allergic inflammation. The aim of this study was to assess eotaxin and ECP levels
      in plasma of atopic asthma patients in stable period of the disease. 19 patients
      with asthma and 10 healthy controls took part in this study. ELISA test was used
      to measure eotaxin (kits from R&D, pg/ml) and ECP (kits from Pharmacia, mg/l)
      levels. Plasma eotaxin level (mean +/- SD) was 176.52 +/- 50.3 (range 89-288) in
      asthma patients and 101.42 +/- 49.4 (range 35-206) in control group (p < 0.001).
      Plasma ECP concentration was 16.7 +/- 6.4 (6.3-28) and 16.8 +/- 17.1 (3.1-61.6),
      respectively (n.s). There was correlation between plasma eotaxin and ECP levels
      (Pearsons correlation co. r = +0.5, p < 0.05) and between eotaxin and FEV1
      (Pearsons correlation co r = -0.4, p < 0.05) in asthma patients. We suggest that
      measurement of eotaxin and ECP levels as well may be useful indicator of disease.

PMID- 10944952
TI  - [Pneumonia in HIV-infected patients: clinical observations].
AB  - OBJECTIVES: To determine the occurrence of pneumonias in HIV-infected patients in
      our hospital during 1990-1999; to evaluate the clinical significance of
      pneumonias in HIV-seropositive patients; to estimate the ethiology of pulmonary
      infection. MATERIALS AND METHODS: One hundred and two HIV-infected patients, 17
      (16.6%) female and 85 (83.3%) male with mean age of 29 +/- 4.5 yrs, were
      retrospectively analysed. All patients had a physical examination particularly
      concerning the clinical symptoms of pulmonary infection, X-ray exam and
      tuberculin skin test (PPD). The stage of HIV infection according to the 1993 CDC
      classification was determined. All patients had the microbiology test of sputum
      (Pc, TB, fungi, other pathogen). In some cases the bronchofiberoskopy with
      bronchoalveolar lavage (BAL) was performed. RESULTS: One hundred and two HIV
      positive patients had 129 episodes of pneumonia. We determine the bacterial
      ethiology in 94/129 (72.9%) cases--TB in 11/129 (8.5%) cases. Fourteen patients
      had 23 episodes of Pneumocystis carinii pneumonia (PcP). Three patients had CMV-
      pneumonitis, detected post mortem. In seven cases the ethiology of pulmonary
      infection was unknown. In summary the ethiology of pneumonia was determined in
      58/129 (44.9%) cases. Thirty three patients were died. The pulmonary infections
      were main cause of death in 23 (67.7%) persons. CONCLUSIONS: In the era of high
      active antiretroviral therapy (HAART) the pulmonary infections in HIV-positive
      patients are the main cause of death as before. The PPD test is useless in HIV
      positive patients. We make a note the increase cases of TB in HIV-infected
      patients during the time of observations.

PMID- 10944953
TI  - [Bone densitometry: interpretation of a single measurement].
AB  - The use of bone densitometry in clinical practice is wide, since it is very
      useful to confirm osteoporosis, predict a fracture or monitor the treatment. In
      some cases the result of a single, sometimes by chance densitometry can provide a
      false conclusion and therapeutic decision when interpreted without sufficient
      knowledge of an individual clinical picture and methodological conditions. A
      number of densitometric analyses were carried out in healthy male showing a
      considerable dispersion in the results. Especially methods used in screening
      studies (SPA, SXA, QUS) provided results lower in contrast to results obtained by
      standard methods (DEXA, QCT). It suggests to be very careful when interpreted the
      result of a single densitometry without personal contact with patient and his
      history, or without sufficient knowledge of densitometric methods.

PMID- 10944954
TI  - [Calcitonin levels in the serum of psoriatic patients].
AB  - In this study the serum calcitonin concentrations were assessed in patients with
      Psoriasis vulgaris. The results were compared with healthy volunteers. The serum
      calcitonin levels of psoriatic patients was significantly increased than in
      healthy volunteers.

PMID- 10944955
TI  - [Fluticasone propionate in the treatment of perennial allergic rhinitis: open
      multicenter trial].
AB  - One hundred and ten patients with perennial allergic rhinitis, currently
      symptomatic, were treated with fluticasone proprionate nasal spray (Flixonase) in
      open, multicentre efficacy and safety study. The drug studied statistically
      significantly decreased all symptoms of the disease conjunctivitis included, in
      the first week of treatment in the patient's and doctor's assessment. The full
      effect of treatment was revealed in the third week. There was significant
      protective effect observed during two weeks after the cessation of treatment.
      Adverse events were mild and occurred in fifteen cases, in two cases could be due
      to the drug (< 2%).

PMID- 10944956
TI  - [Hemothorax and retroperitoneal hematoma with the secondary posthemorrhagic
      anemia as a complication of oral anticoagulant and non-steroidal anti
      inflammatory drug therapy].
AB  - The authors want to indicate, according to the case description, the danger of
      oral anticoagulants and nonsteroidal antiinflammatory drug's therapy in elderly
      patients.

PMID- 10944957
TI  - [Diagnostic difficulties and unfavorable course Wegener's granulomatosis in 1
      year-old girl].
AB  - We described an 11 year old girl who presented and unusual clinical course of
      Wegener's granulomatosis (WG). The rapidly progressive glomerulonephritis was the
      onset of the illness. The characteristic manifestation of WG from the respiratory
      tract was observed after 1.5 year from the beginning of the disease. Inspite of
      intensive treatment the end-stage renal failure developed and progress of the
      disease was observed. These complications caused patient's death.

PMID- 10944958
TI  - [Viral infection, the mask of decompression sickness and decompression sickness
      diagnosed as viral infection].
AB  - Two cases of diving persons: a soldier from the military centre of divers
      training and a student amateur diver, have been presented in the study. On the
      basis of similar symptoms--among others: muscular pain, discomfort, subfebrile
      body temperature, extremely different, incorrect diagnoses were given and
      improper treatment was introduced. In the case of the soldier suffering from a
      viral infection decompression sickness was diagnosed only because he served in a
      divers unit. Whereas, in the second case a physician did not take into
      consideration all available history data and diagnosed influenza despite evident
      symptoms of decompression sickness. In the discussion the factors which should
      have guided the physician in both cases to proper diagnosis and proper
      therapeutic management have been indicated.

PMID- 10944959
TI  - [The role of heparin in allergic inflammation].
AB  - Heparin is a glycosaminoglican used in prophylactic and treatment of thrombosis.
      Heparin possesses also non-anticoagulant properties, including modulation of
      various proteases, anticomplement activity, and anti-inflammatory actions.
      Inhaled heparin has been shown to reduce early phase of asthmatic reaction and
      suppress allergen induced rise in bronchial hyperreactivity. Heparin inhibits the
      acute cutaneous reaction due to allergens. Moreover, inhaled heparin prevents
      exercise-induced asthma. The exact mechanism of heparin action in bronchial
      asthma remains obscure. It has been observed that heparin acts as a specific
      blocker of IP3 receptors and inhibits IP3-mediated calcium release in various
      cell types, including vascular smooth muscle and airway smooth muscle. In this
      mechanism heparin inhibits allergen induced mast cell degranulation and prevents
      subsequent development of reaction cascade leading to inflammation, bronchial
      hyperreactivity and asthma. It also modulates migration of proinflammatory cells,
      eosinophils and neutrophils, into the site of allergic reaction. Furthermore,
      heparin inhibits the increased vascular permeability induced by a wide range of
      agonists acting via specific receptors located on the vascular endothelial cells.
      The cationic peroxidases, such as major basic protein and eosinophil peroxidase,
      are neutralized by the highly anionic heparin; thus heparin inhibits the
      epithelial damage induced by some of these cationic proteins. The mechanism
      involved in the control of bronchial hyperreactivity by heparin has been studied
      little and is yet poorly understood. Heparin deserves further investigations in
      large number of subjects to provide further insight into the pathophysiology of
      asthma. Heparin may also be of clinical importance and may form the basis of
      novel therapeutic approaches.

PMID- 10944960
TI  - [New aspects of use inhaled steroids in treatment of children with bronchial
      asthma].
AB  - The development of potent glucocorticoids (GC) delivered topically via metered
      dose inhalers (MDI) have revolutionized the way we care for asthmatic children.
      Steroids can improve asthma symptoms, baseline pulmonary function, and reduce
      bronchial hyperresponsiveness (BHR) to the extent no other asthma medication can.
      In addition, the fact that small quantities of GC are delivered topically, the
      incidence of adverse effects is greatly diminished. Inhaled GC therapy has become
      first line therapy for all children even with mild persistent asthma, and their
      early use in life is known as "early intervention". The results from many studies
      suggest that the longer the time from the initiation of symptoms, and subsequent
      treatment with inhaled GC, the less effective this form of therapy may be. Also,
      early intervention and long-term therapy may offer the potential to effect long
      term outcome. Unfortunately, systemic absorption does occur, and with that comes
      the potential for adverse effects. Growth suppression and bone metabolism effects
      remain the most feared, controversial, and inadequately addressed issues facing
      long-term inhaled GC therapy. In general, the development of adverse effects from
      inhaled GC therapy is dependent on the dose and the frequency with which the
      inhaled GC is given. They can also be minimized by using a spacer device,
      turbuhaler, mouth rinsing. It is important to define maximally safe and effective
      doses of the available inhaled GC and corresponding delivery systems.

PMID- 10944961
TI  - [Immunogenic Mycobacterium tuberculosis heat shock protein in tuberculosis].
AB  - The heat shock protein (hsp) are produced by prokaryotic and eukaryotic cells in
      the response to a increase in temperature and a variety of insults. Hsp have been
      defined by their apparent molecular weight as family: Hsp100, Hsp90, Hsp70,
      Hsp60, Hsp40 and SHsp (15-25 kD). Analysis of the immune response of M.
      tuberculosis infected individuals allowed for identification of antigens of
      tubercle bacilli. Most of them belong to evolutionarily highly conserved hsp,
      which cross-reactive with the hsp of E. Coli. It is conceivable that in a
      tuberculous granuloma both pathogenes and host cells are stressed and produce
      hsp. The heat shock proteins with molecular weight of 71 kD, 65 kD, 10-16 kD are
      immunogens and a functional role as molecular chaperones. The literature on the
      immunology of hsp in infectious diseases is complex and confusing and it is still
      not clear whether host immune responses to these proteins are protective, or
      damaging, as they may lead to the induction of autoimmunity. The study is engaged
      in a role of others mycobacterial hsp in host immuno-reactivity and their
      compliance with treatment of infectious diseases, neoplastic genic therapy or/and
      with more powerful antimycobacterial vaccine.

PMID- 10944962
TI  - [The influence of thyrotoxicosis and thyroxine therapy on the risk of
      osteoporosis].
AB  - The review presents data from literature on the influence of endogenous and
      exogenous thyroid hormones on the activity of bone resorption and formation
      followed by enhanced bone loss and risk of osteoporosis. Thyroid hormones
      represent commonly prescribed medicines, often are used without control of their
      effects, especially in older patients at risk of fractures due to osteoporosis.
      The fracture risk increases in cases of untreated thyrotoxicosis, when
      administered suppressive doses of thyroxine, in postmenopausal women and patients
      with low peak bone mass. Fractures are more likely in parts of skeleton with
      cortical bone predominance e.g. distal forearm and hip.

PMID- 10944963
TI  - [Vaccination against influenza and Guillain-Barre syndrome: are there any
      relations?].
AB  - Influenza, a disease known for centuries, continues to be a major medical problem
      throughout the world with substantial economical and health impact. The risk of
      death related to influenza is higher among individuals over 65 years of age and
      those with chronic diseases. Vaccination against influenza was successfully
      applied in massive prophylaxis of the disease in different countries for many
      years. Although there are some well known and monitored adverse reactions to
      influenza vaccines, the evidence whether influenza vaccination might be causally
      associated with higher risk of Guillain-Barre syndrome is not clear. In this
      paper the available literature data concerning this problem were reviewed. Own
      experiences on influenza vaccination and plasmapheresis treatment of Guillain
      Barre syndrome were presented.

PMID- 10944964
TI  - [Allergology in internet].
AB  - The authors present all-Polish Internet Allergy Service www.allergen.info.pl
      working since February 1998. The system of mailing current allergenic pollen data
      to individual patients is presented. The results of Internet questionnaire filled
      by 4500 users of GlaxoWellcome Pollen Count Internet Service in 1998 are
      discussed. The authors also present possibility of cooperation for clinicians
      with the usage of IRC and picture and voice transmission.

PMID- 10944965
TI  - [Evolution of somatic and psychological symptoms in patients hospitalized for
      pulmonary tuberculosis complicated with neurotic anxiety reactions in the course
      of the treatment].
AB  - Evolution of both somatic and psychic symptoms in patients with pulmonary
      tuberculosis complicated and non-complicated with neurotic anxiety reactions has
      been studied. Comparative analyses have shown that patients with tuberculosis
      complicated by neurotic anxiety reactions have markedly lower psychic and somatic
      immunity, probably delaying the achievement of negative sputum in the foreseen
      period of time. This phenomenon requires further studies. A role of basic
      psychotherapy in the phthisiology, and psychophysiological biofeedback is
      emphasized.

PMID- 10944966
TI  - [Heart failure, higher morbidity, lower mortality. Are we on the right path?].

PMID- 10944967
TI  - [Prognostic stratification of unstable angina controlled with medical treatment:
      is the stress test sufficient?].

PMID- 10944968
TI  - [Documents of cardiovascular prevention: a global view].

PMID- 10944969
TI  - [Geographic variation in hospitalizations and mortality related to congestive
      heart failure in Spain, 1980-1993].
AB  - BACKGROUND AND OBJECTIVES: Geographical differences in hospitalizations and
      mortality for heart failure serve to estimate the potential for reducing the
      associated hospital and demographic burden on the population. Accordingly, the
      objective of this paper is to analyze the geographic variation in heart failure
      hospitalizations and mortality in Spain during the period of 1980-1993, and to
      examine their potential determinants. METHODS: Data on the primary diagnosis of
      heart failure were taken from the National Hospital Morbidity Survey and National
      Vital Statistics. Information on determinants of heart failure were obtained from
      large-scale nationally representative surveys conducted by the National
      Statistics Office. RESULTS: The period of 1980-1993 witnessed a decrease in
      geographical differences in heart failure hospitalizations and mortality.
      Theoretically, however, heart failure hospitalizations and mortality among
      persons aged > or = 45 years could still be further reduced by 60% and 30%
      respectively. In the period of 1989-1993 heart failure hospitalizations were
      correlated (p < 0.05) with ischaemic heart disease hospitalizations and the
      number of beds/1,000 inhabitants. Heart failure mortality showed a statistically
      significant correlation (p < 0.05) with ischaemic heart disease mortality,
      illiteracy and unemployed status. CONCLUSIONS: There is a great potential for a
      reduction in the hospital and demographic burden of heart failure in Spain.
      Control of ischaemic heart disease and a reduction in the geographical
      differences in socio-economic status would probably contribute to lessening the
      healthcare burden of heart failure in Spain.

PMID- 10944970
TI  - [Low risk stress test in patients with unstable angina: does it imply a favorable
      prognosis?].

PMID- 10944971
TI  - [Subacute thrombosis with antiplatelet treatment in a non-selected population of
      intracoronary stents: incidence and predictors].
AB  - INTRODUCTION: After coronary stenting, the incidence of subacute stent thrombosis
      have been reduced to 0% using aspirin and ticlopidine, in studies with selected
      populations and intracoronary ultrasounds. OBJECTIVE: To evaluate the incidence
      and predictors of subacute stent thrombosis in a nonselected population, using
      antithrombotic therapy. METHODS: We studied 285 stents, consecutively and
      successfully implanted in 268 lesions of 226 patients. We used high pressure
      balloon inflation without intracoronary ultrasound. Post-stenting protocol
      included aspirin and ticlopidine during four weeks with no anticoagulation. We
      defined subacute stent thrombosis as death, acute myocardial infarction
      myocardial infarction or angiographic occlusion of stent, with TIMI flow 0-1,
      after the first 24 hours and during the first month. RESULTS: Four patients
      presented events (1.7%): Three nonfatal myocardial infarction after discharge,
      with documented angiographic thrombosis of stent, and one death due to in
      hospital myocardial infarction. All three non-fatal AMI, occurred in vessels less
      than 3 mm (p = 0.07) and in patients taking aspirin without ticlopidine (p <
      0.001). After discharge, three (17%) of 18 patients with inadvertent
      discontinuation of ticlopidine presented subacute stent thrombosis, in contrast
      to none of 25 patients taking ticlopidine without aspirin. Excluded patients with
      discontinuation of ticlopidine, the incidence of subacute stent thrombosis was
      0.5%. CONCLUSION: After intracoronary stenting in a nonselected population, using
      antithrombotic treatment with aspirin and ticlopidine, we may expect a rate of
      subacute stent thrombosis about 1%. Ticlopidine seems to have the main role in
      preventing subacute stent thrombosis, above all in predisposing circumstances as
      small vessels.

PMID- 10944973
TI  - [Prospective and comparative study of pacemaker implants carried out at the
      electrophysiology laboratory and the operating room].
AB  - INTRODUCTION AND OBJECTIVES: Permanent pacemaker implantation is done by
      different physicians with either a surgical or clinical training. Our objective
      was to evaluate if there were significant differences in the implantation
      parameters and in the complication rate among implantations performed by
      cardiologists in the electrophysiologic laboratory and cardiological surgeons in
      the operating room. MATERIAL AND METHODS: We prospectively collected those
      patients' data who received a first pacemaker implantation by cardiovascular
      surgeons and electrophysiologists during the year 1998. Data collected included
      demographic information, indication for pacing, surgical time, complications
      during procedure, stimulation and sensing thresholds as well as type of pacing.
      RESULTS: We first-implanted 216 pacemakers in a one year period, 101 by
      cardiovascular surgeons and 115 by electrophysiologists. 56% were male patients.
      Average age in the surgery group was 74.2 +/- 9 years and 72.09 +/- 12 in the
      electrophysiology group (p = NS). Main diagnoses were as follows: complete heart
      block in 32.9% patients, complete heart block 2. degrees 16.4%, sinus node
      dysfunction 12.2%, AV node ablation 12.2% and others. The complications rate for
      surgery group was 4% and 1.7% for electrophysiologists (p = NS).
      Electrophysiologists placed more bicameral devices. No clinically significant
      differences were found among other implant parameters. CONCLUSIONS: Pacemaker
      implant by cardiologists in an electrophysiologists laboratory is a safe
      procedure that does not have more complications when compared to the same
      procedure done in the operating room by surgeons. This allows hospital resource
      optimization and reduction of hospital stay length.

PMID- 10944972
TI  - [Primary stent implantation in aortic coarctation: mid-term follow-up].
AB  - BACKGROUND: The use of balloon-expandable stents provides an effective
      alternative therapy in patients with stenotic lesions in congenital heart
      disease. Stents implantation has served to improve the results and to reduce
      complications of balloon angioplasty for coarctation and recoarctation of the
      aorta. OBJECTIVE: We report our results after primary stents implantation for
      coarctation and recoarctation of the aorta. PATIENTS AND METHODS: Balloon
      expandable stents were implanted in 14 patients (mean age 20 +/- 12 years) with
      coarctation of the aorta (11 native and 3 postoperative); 2 patients had
      associated malformations. The morphology varied: 10 resembled a located-diaphragm
      (one of them with moderate arch hypoplasia); 2 had distorted coarctation and 2
      had a complete aortal obstruction. Five patients were hypertensive and 1 had
      cardiogenic shock and severe arrhythmias which did not respond to intensive
      medical therapy. In all cases 14 Palmaz stents (7 P308 and 7 P4014) were
      implanted with the primary technique through a Mullin's sheath. The balloon-to
      descending aorta diameter ratio, measured at the level of the diaphragm, was 1. A
      special technique was carried out in the 2 cases with complete aortal
      obstruction. RESULTS: The procedure was effective in all 14 cases. The
      coarctation diameter increased from 4 +/- 2 to 15 +/- 2 mm (p < 0.0001) and
      transcoarctation systolic pressure gradient decreased from 43 +/- 19 to 2 +/- 2
      mmHg (p < 0.0001). The ratio of the coarctation to descending aorta diameter
      measured at the level of the diaphragma increased from 0.3 +/- 0.1 to 0.95 +/-
      0.05 (p < 0.001). At 19 +/- 8 months follow up, all patients showed sustained
      clinical improvement. The patient with complete aortal obstruction experienced a
      dramatic improvement, but she died from a sudden cardiac event 22 months after
      the procedure. At angiographic follow up in 7 patients, 1 year after
      implantation, no recoarctation was observed with secondary vessels patent, and
      absence of restenosis. CONCLUSIONS: a) Percutaneous endovascular stents
      implantation in coarctation and recoarctation of the aorta may become an
      effective treatment modality in the older child, adolescent and adults; b) stents
      are particularly attractive in those patients with a more complex anatomy and
      higher surgical risk; c) primary stenting is expected to have a lower rate of
      complications, and d) we describe a special technique with a right femoral-left
      humeral arterial circuit that is successfully applied to patients with complete
      aortal obstruction.

PMID- 10944974
TI  - [Total anomalous pulmonary venous return in children: importance of
      echocardiographic diagnosis and early surgery].
AB  - OBJECTIVE: We studied patients who underwent surgical repair for total anomalous
      pulmonary venous return at our hospital. We report the importance of diagnosis by
      echocardiographic imaging before surgical treatment. METHODS: Within the period
      of 1990-1999, fourteen patients underwent surgical repair of this cardiopathy in
      our hospital. The type of anomalous drainage was supracardiac in 6 patients,
      infracardiac in 4, to the coronary sinus in 1, and mixed-type in 3 patients.
      Eleven cases were diagnosed with an echo-Doppler study, the findings being
      confirmed intraoperatively. RESULTS: There were 2 early deaths: one occurred in
      the operating room in a patient with a small left ventricle, and the second one
      was 35 days postoperatively as a result of a septic complication. Early in the
      postoperative period our primary goal has steadily been the control and treatment
      of pulmonary hypertension. After a mean follow-up time of 50 months, only 1
      patient needed to be reoperated on and the remainder are symptomless.
      CONCLUSIONS: That sufficient diagnostic data on total anomalous pulmonary venous
      return can reliably be obtained by ultrasound scanning so that surgery can be
      promptly undertaken, and that its surgical risk is currently low and mid-term
      post-repair outcome is fairly good.

PMID- 10944975
TI  - [Control of cholesterolemia in Spain, 2000. A tool for cardiovascular
      prevention].
AB  - The document "Cholesterolemia Control in Spain, 2000: A Tool for Cardiovascular
      Disease Prevention" reviews the current evidence on cardiovascular disease
      prevention and the therapeutic advances achieved in recent years, in order to aid
      risk-based clinical decision-making. Cardiovascular diseases rank as the first
      cause of death in Spain. Their demographic, health and social impact is
      increasing and it is likely to continue to do so in the next decades. Appropriate
      treatment for high blood cholesterol and other major risk factors is crucial in
      cardiovascular disease prevention. Individual risk stratification is essential to
      determine follow-up periodicity and treatment. Priorities for the control of
      cholesterolemia and the consequent cardiovascular risk are based on risk
      stratification. In primary prevention, the therapeutic objective in high risk
      patients has been established as LDL-cholesterol < 130 mg/dl. In secondary
      prevention, drug treatment is indicated when LDL-cholesterol > or = 130 mg/dl and
      the therapeutic objective is LDL-cholesterol < 100 mg/dl. Statins are first line
      drugs for treatment of high blood cholesterol. In moderate-severe
      hypertriglyceridemia or low HDL-cholesterol, fibrates are preferred. In acute
      coronary syndrome, hypolipemiant treatment, should be started as soon as
      possible, when indicated. Secondary prevention programmes that continually
      provide good clinical and risk factor control should be provided to coronary
      heart disease patients.

PMID- 10944977
TI  - [Sudden cardiac death out of the hospital and early defibrillation].
AB  - Since most sudden cardiac death victims show neither symptoms before the event
      nor other signs or risk factors that would have identified them as a high risk
      population before their cardiac arrest, emergency out-of-hospital medical
      services must be improved in order to obtain a higher survival in these patients.
      Early defibrillation is an essential part of the chain of survival that also
      includes the early identification of the victim, activation of the emergency
      medical system, immediate arrival of trained personnel who can perform basic
      cardiopulmonary resuscitation and early initiation of advanced cardiac life
      support that would raise the survival rate for sudden cardiac arrest victims.
      Many studies have demonstrated the enormous importance of early defibrillation in
      patients with a cardiac arrest due to ventricular fibrillation. The most
      important predictor of survival in these individuals is the time that elapses
      until electric defibrillation, the longer the time to defbrillation the lower the
      number of patients who are eventually discharged. Multiple studies have
      demonstrated that automatic external defibrillation will reduce the time elapsed
      to defibrillation and thus improve survival. For these reason, public access
      defibrillation to allow the use of automatic external defibrillators by minimally
      trained members of the lay public, has received increasing interest on the part
      of a groving number of companies, cities or countries. The automatic external
      defibrillaton, as performed by a lay person is being investigated. The
      liberalization of its application, if is demonstrated to be effective, will need
      to be accompanied by legal measures to endorse it and appropriate health
      education, probably during secondary education.

PMID- 10944976
TI  - [Clinical practice guidelines of the Spanish Society of Cardiology on unstable
      angina/infarction without ST elevation].
AB  - This paper up-dates the Clinical Guidelines for Unstable Angina/Non Q wave
      Myocardial Infarction of the Spanish Society of Cardiology. Due to the increased
      efficacy of adequate management in the early phases, it has been considered
      necessary to include recommendations for the pre Hospital and Emergency
      department phase. Prehospital management. Patients with thoracic pain compatible
      with myocardial ischemia should be transferred to Hospital as quickly as possible
      and an ECG tracing performed. Initial management includes rest, sublingual
      nitroglycerin and aspirin. In the Emergency department. Immediate clinical
      attention and accessibility to a defibrillator should be available. If ECG
      tracing discloses ST elevation reperfusion strategy is to be implemented
      immediately. If no ST elevation is present, the probability of myocardial
      ischemia and risk factor evaluation is essential for adequate management. A
      simplified risk stratification classification is presented, that also determines
      the most adequate site for admission: Coronary Care Unit if high risk factors are
      present, Cardiology ward for the intermediate risk patient and ambulatory
      treatment if low risk. Management in Coronary Care Unit. Includes routine ECG
      monitoring and analgesia. Antithrombotic and anti ischemic treatment include new
      indication for GP IIb-IIIa and Low molecular weight heparins. Coronary
      arteriography and revascularisation are recommended, if refractory or recurrent
      angina, left ventricles dysfunction or other complications are present.
      Management in the ward is based on adequate chronic medical treatment, risk
      stratification, and secondary prevention strategy. Coronary arteriography before
      discharge must be considered in the light of the result of non-invasive tests.

PMID- 10944978
TI  - [Preservation of mitral subvalvular apparatus with disc prosthesis].

PMID- 10944979
TI  - [Aspiration of large intracoronary thrombus after apparently successful
      angioplasty. Therapeutic implications].
AB  - We present a case in which, after performing an optimal angioplasty after an
      acute myocardial infarction with intracoronary thrombus, normal coronary flow was
      not achieved. After aspirating through the guiding catheter we obtained a large
      thrombus that the histopathologic study confirmed as a recent thrombus and,
      subsequently, normal flow was reestablished. The procedure was completed with a
      successful intracoronary stent implantation, with an uneventful clinical course.
      The therapeutic and diagnostic implications of this case are discussed.

PMID- 10944980
TI  - [Interrupted aortic arch with aortopulmonary window. Total primary correction
      without extracorporeal circulation in the newborn].
AB  - This report describes the unusual association between the interruption of the
      aortic arch type B and aortopulmonary window type II in a neonate. When the
      patient was 20 days old, a one-stage surgical repair was done through left side
      thoracotomy without circulatory by-pass, making a left carotid artery to
      descending aorta anastomosis, closing the window with a hemaclip, respectively. A
      routine 2-D Doppler color echocardiography performed in the immediate
      postoperative period showed the absence of blood flow in the right pulmonary
      artery. The patient required a new intervention, changing the position of the
      clip in order to restore the normal pulmonary blood flow. Eight months after
      surgery, the "neoaortic arch" grows in harmony with the body surface area,
      without signs of cerebral circulatory deficiency or significant gradient at any
      level.

PMID- 10944981
TI  - [Traumatic rupture of tricuspid valve: report of 3 cases].
AB  - Tricuspide valve lesions due to non-penetrating trauma are rare and their
      diagnosis is difficult. Nevertheless, over 100 cases of post-traumatic valve
      regurgitation have been described in the last 35 years. We present 3 such cases
      diagnosed and operated at our center in the last 8 years.

PMID- 10944982
TI  - [Anterograde decremental conduction by left free wall accessory pathway in the
      permanent form of junctional reciprocating tachycardia].
AB  - We present the case of a 2-month-old infant, diagnosed prenatally with
      tachycardia. The characteristics of the surface electrocardiogram were consistent
      with the diagnosis of the permanent form of junctional reciprocating tachycardia:
      narrow-complex tachycardia at 200 beats/min, negative P' wave in inferior leads
      (II, III, aVF), I, aVL and from V4 to V6. The tachycardia was incessant despite
      medical treatment with digoxin, quinidine, amiodarone and flecainide. The
      electrophysiological study confirmed that the mechanism of the tachycardia was a
      left posterolateral pathway with long conduction time and decremental properties.
      The ablation procedure was tried by transseptal approach. During transseptal
      puncture complete atrioventricular block and interruption of the tachycardia were
      produced. Decremental ventricular preexcitation was evident during isoproterenol
      infusion. After recovery of the atrioventricular conduction and incessant
      tachycardia, radiofrequency ablation of the pathway was performed twelve months
      later by retrograde approach.

PMID- 10944983
TI  - [Usefulness of the ultrasonography contrast media levovist-levograf in the
      diagnosis of aortic stenosis in the elderly].

PMID- 10944984
TI  - [Pacemakers, defibrillators, and electromagnetic environment: potential
      interactions with electronic mechanisms of surveillance should not be cause of
      anxiety for patients].

PMID- 10944985
TI  - [Prevention of cardiovascular diseases: should the same criteria be applied in
      Latin America and Europe and North America?].
AB  - The prevention of cardiovascular diseases is based on the management of known
      cardiovascular risk factors by pharmacological means or by modifying lifestyles.
      A reduction in cholesterol levels is associated with a lower incidence of
      cardiovascular events and mortality, in both primary or secondary prevention
      trials. A reduction in blood pressure also leads to a decrease in acute
      myocardial infarction and the incidence of stroke. Regular exercise is associated
      with better disease free survival and the effects of smoking cessation are well
      known. High homocysteine levels are also associated with cardiovascular disease.
      However, there are no prospective clinical trials showing a beneficial effect of
      homocysteine reduction on cardiovascular mortality. A change in the type of
      dietary fat should also be beneficial, but this has not been proven in
      prospective clinical trials. In Chile, cardiovascular diseases are the leading
      cause of death among adults and the prevalence of cardiovascular risk factors,
      including hyperhomocysteinemia is similar to that of European or North American
      populations. Successful primary and secondary prevention programs to manage these
      risk factors have been developed in Chile. Therefore, the criteria applied in
      North America and Europe for the prevention of cardiovascular diseases, should be
      applied with slight modifications, in Latin American Countries.

PMID- 10944986
TI  - [Non-invasive elements in the assessment of myocardial viability: a continuous
      search].

PMID- 10944987
TI  - [Unstable angina in the elderly: are the differences in diagnostic and
      therapeutic approaches justified? The concept of the "younger old" and the "older
      old"].

PMID- 10944988
TI  - [Efficacy of stress-rest myocardial SPET with 99mTc-MIBI in predicting recovery
      of postrevascularization contractile function. Results of the Spanish multicenter
      protocol. Working Group of Nuclear Cardiology].
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of
      stress-rest 99mTc-MIBI SPET to predict wall motion improvement after
      revascularization. MATERIAL AND METHODS: A prospective and consecutive series of
      82 patients (59 +/- 9 years, 12 women), who had some segment with severe
      impairment of the contractility and underwent coronary revascularization by
      surgery (n = 64) or angioplasty (n = 18) were studied with rest 99mTc-MIBI SPET.
      All patients had a rest 99Tc-MIBI SPET, and an exercise test was also performed
      on 40 of these patients. Before and within 3-6 months after the revascularization
      a gated blood pool scintigraphy of three projections was performed. The
      segmentary contractile recovery after revascularization was assessed in relation
      to the quantification of the 99mTc-MIBI uptake and to the exercise-rest
      reversibility (exercise uptake < rest uptake). RESULTS: The mean value of the
      left ejection fraction did not change after the revascularization (41.1 +/- 14.5%
      vs 41.8 +/- 15.7%). In the post revascularization control a contractile recovery
      was observed in 40% (113/282) of the segments with severe hypokinesia, akinesia
      or dyskinesia. Exercise-rest reversibility and rest uptake > 30% were present in
      62% (p = 0.002) and 89% (p < 0.0001) respectively of segments that improved
      contractility after revascularization. CONCLUSIONS: For the 99mTc-MIBI SPET an
      exercise-rest reversibility and > 30% uptake at rest are predictive criteria of
      contractile recovery after revascularization.

PMID- 10944989
TI  - [Management of unstable angina: advanced age is still an independent predictive
      factor of more conservative management after prognostic stratification with
      stress test].
AB  - BACKGROUND AND OBJECTIVE: In the management of ischemic heart disease, elderly
      patients constitute a subgroup that, despite having a worse prognosis, are
      usually managed more conservatively. The objective of this study was to evaluate
      if, in the management of unstable angina, a more conservative attitude in elderly
      patients is maintained after stratification by exercise test. PATIENTS AND
      METHODS: The study population is constitude by 859 patients admitted to hospital
      due to suspected unstable angina that were referred to exercise test after
      medical stabilization. The management (invasive versus conservative, according to
      submission to cardiac catheterization or not) of patients was retrospectively
      studied, comparing patients < or = 70 versus > 70 years-of age. RESULTS: Out of
      the 859 patients, 156 (18%) were > 70 years old, and the exercise test was
      positive in 281 (33%). Cardiac catheterization was performed in 494 (57%): 62% in
      older and 38% in younger patients (p < 0.0001). Other characteristics associated
      with a more conservative management were: a negative exercise test, > 85% of the
      maximum heart rate, duration of exercise test more than 6 minutes, female gender,
      smoking and absence of episodes of rest angina. In the multivariate analysis, the
      statistically significant characteristics associated with an invasive management
      were the result of the exercise test (OR for positive result: 4.50; IC 95% = 2.73
      7.63; p < 0.0001), the duration of exercise (OR for > or = 6 minutes: 0.51; IC
      95% = 0.29-0.88; p = 0.0177), the percentage of the maximum heart rate (OR for >
      or = 85%: 0.65; IC 95% = 0.42-0.98; p = 0.0391) and age (OR for > 70 years 0.36;
      IC 95% = 0.20-0.62; p = 0.0004). CONCLUSIONS: In the management of unstable
      angina, elderly patients constitute a more conservatively managed subgroup even
      after risk stratification with exercise test.

PMID- 10944990
TI  - [Severe abdominal complications in patients treated with heart transplantation:
      the problem of clinical inexpressiveness].
AB  - INTRODUCTION: In transplanted patients, immunosuppressive drugs can mask habitual
      pathologies that impede their diagnoses and management. Abdominal pathology gives
      up to 2-20%, 50% of which is surgical, with a mortality of 10-40%. The most
      frequently detected pathologies are: acute pancreatitis, peptic ulceration and
      intestinal obstruction. OBJECTIVES: To determine the alarm parameters, more
      adequate diagnostic procedures and the most frequent causes of morbidity and
      mortality in order to attempt to avoid them. METHODS: In our center 225 heart
      transplantations were performed from May 1984 to October 1997. The severe
      abdominal complications, time of appearance, implication of immunosuppressive
      drugs and presence of rejection were studied in these patients. RESULTS: 35
      severe abdominal complications were detected (incidence 12.9%), with the majority
      differing (> 1 year following transplant). The most frequently detected
      pathologies were digestive hemorrhages and perforations. Acute pancreatitis was
      11%. The immunosuppressive drugs used were prednisona, cyclosporin and
      azathioprine. In 12 out of 29 patients the abdominal complication was in the
      context of acute rejection. CONCLUSIONS: Even with some non-specific abdominal
      symptoms in these group of patients it is important to rule out severe
      pathologies such as acute pancreatitis or empty viscera perforation. The
      detection of amylases and lypases in the blood and an echographic or tomographic
      abdominal study should be performed early with a digestive hemorrhage it is
      important to perform an endoscopy. If the surgical intervention seems imminent
      it's better to perform it without any delay, because it has been demonstrated
      that the delay is worse than the probable rejection.

PMID- 10944992
TI  - [Endocardial ablation of substrate of postinfarction ventricular tachycardia
      during sinus rhythm].
AB  - OBJECTIVE: Radiofrequency ablation of ventricular tachycardia requires good
      tachycardia tolerance during mapping and entrainment, and this limits its
      application. We present our initial experience with ventricular tachycardia
      ablation during sinus rhythm in 7 patients with previous inferior myocardial
      infarction. METHODS: Seven men, 56-70 years old (mean +/- SD, 65 +/- 4.5) were
      included in the study. Ventricular tachycardia was unstable in 6 and in 1 it was
      induced non-sustained. The scar was localized by recording low-voltage,
      fragmented electrograms (< 2 mV). Ventricular tachycardia "exit" was localized by
      pace-mapping in sinus rhythm. Radiofrequency lines were made radially, point by
      point, from normal to scarred tissue. One of the lines crossed the exit area. The
      objective was to achieve non-inducibility. RESULTS: Sustained clinical
      ventricular tachycardia was induced in 6 and non-sustained in 1. Two-four lines
      were performed per patient with 11-28 (21 +/- 5.4) radio frequency applications.
      The procedure duration was of 130-280 min (230 +/- 61) and being 49-75 min (63 +/
      7.9) for fluoroscopy. There were no complications. Clinical ventricular
      tachycardia became non-inducible in 6, although in 4 a rapid (cycle < or = 250
      ms), non-clinical ventricular tachycardia remained inducible. Defibrillators were
      implanted in the patient remaining inducible for clinical ventricular tachycardia
      and another with > 60 tachycardia episodes the previous week. During 3-22 months
      (13.8 +/- 5.9) of follow-up, 1 patient died of heart failure at 20 months and
      another received 3 defibrillator shocks for VT at 13 months. There were no other
      episodes of ventricular tachycardia, syncope or sudden death. CONCLUSIONS: This
      preliminary experience suggests that radiofrequency ablation of post-infarction
      ventricular tachycardia substrate is possible during sinus rhythm, suggesting
      that radiofrequency ablation may be applicable in a large proportion of patients
      with post-infarction sustained ventricular tachycardia.

PMID- 10944991
TI  - [Heart failure caused by severe systolic ventricular dysfunction of hypertensive
      origin. Long-term clinical and functional course].
AB  - AIMS: The aims of our study were to evaluate survival and evolution of functional
      class and ventricular function in patients with severe congestive heart failure
      due to dilated cardiomyopathy. METHODS: Inclusion criteria were: class III or IV
      heart failure, dilated left ventricle with ejection fraction < 40%, history of
      poor controlled hypertension, and exclusion of other etiologies for heart
      failure. We studied 17 patients with these features; mean age was 64 +/- 7 years
      and 70% were male. They were followed up during a mean period of 3.3 +/- 1 years
      (2 to 6; median 3 years). RESULTS: Baseline left ventricular ejection fraction
      was 30 +/- 5% (20 to 40); 35% of patients were in functional class III and 65% in
      class IV; 100% of patients received ACE inhibitors and diuretics, 53%
      betablockers, and 35% calcium-antagonists. Survival was 100%. Left ventricular
      ejection fraction increased from 30 +/- 5% to 44 +/- 11% at one year, to 50 +/-
      11% at 3 years and 51 +/- 10% at the end of follow-up (p < 0.001). This
      improvement was mainly due to a reduction in systolic left ventricular diameter
      (from 51 +/- 4 mm to 42 +/- 11 mm, p < 0.01), since diastolic diameter did not
      significantly changed (63 +/- 4 to 59 +/- 11 mm). CONCLUSIONS: The evolution of
      severe systolic left ventricular dysfunction due to arterial hypertension is
      favourable at long-term, with null mortality and clinical ejection fraction and
      functional improvement. Nevertheless, the persistence of left ventricular
      dilatation suggests that myocardial damage caused by chronic pressure overload
      does not disappear.

PMID- 10944993
TI  - [Coxiella burnetii endocarditis: long-term clinical course in 20 patients].
AB  - INTRODUCTION AND OBJECTIVES: Coxiella burnetii is a causative agent of
      increasingly frequent subacute infective endocarditis, and is associated with
      elevated morbimortality. Our aim in the present study was to assess the clinical,
      serological and therapeutic long-term evolution of 20 patients with Coxiella
      burnetii endocarditis. METHODS: Twenty patients (13 male and 7 female, age 42 +/-
      10 years) admitted between 1982 and 1996 were retrospectively studied. All of
      them fulfilled the Duke criteria modified by Raoult for Q fever endocarditis.
      RESULTS: Endocarditis involved prosthetic and native valves in 14 and 6 patients,
      respectively. All patients except one received antibiotic treatment. Patients
      treated with doxycycline in monotherapy showed worse evolution than those treated
      with doxycycline in combination with other antibiotics. Valve replacement was
      performed in 15 patients, due to prosthetic dysfunction in most of them. The
      overall mortality was 40% (8 patients). At follow-up of 74 months (range 19-156)
      (mean 74 +/- 47) all patients showed persistent high levels of phase I
      antibodies. At follow-up of 15 to 65 months (32 +/- 30) antibiotic treatment was
      suspended in five patients because they were asymptomatic and without
      microbiologic findings of valvular endocarditis. CONCLUSIONS: Q fever
      endocarditis was associated with severe complications, which often required valve
      replacement. All patients showed persistent high serological titers of Coxiella
      burnetii endocarditis without other signs of active infection. This finding
      raises the issue of suspending antibiotic treatment in patients with negative
      microbiologic findings and questions the persistence of abnormal serology as a
      monitor of treatment efficacy.

PMID- 10944994
TI  - [Clinical practice guidelines of the Spanish Society of Cardiology on
      pacemakers].
AB  - Following a brief introduction on the history and generic codification of the
      different cardiac stimulation methods available, the implantation techniques are
      described and the requisites, such as human resources, their qualifications and
      the materials required, which are essential in the organization of a Pacemaker
      Unit are discussed. The current indications for permanent cardiac stimulation are
      reported and are classified by sections in tales following the 1998 norms of the
      ACC/AHA. In another section, the indications in special situations such as
      hypertrophic or dilated cardiomyopathy are described. Stimulation frequency
      modulation with the incorporation of biodetectors in modern pacemakers or in the
      probes are commented upon as is atriosynchronic ventricular stimulation with a
      single electrode (VDD). The recent automatisms which have been implemented in the
      current pacemakers are discussed and the most adequate selection of the
      stimulation mode for each patient is analyzed and demonstrated in a table which
      may be easily interpreted. On establishing the recommendable protocol for
      undertaking the follow up of the patient with a pacemaker, the criteria accepted
      as replacement indicators are discussed. In a brief section some legal aspects
      (drivers license, informed consent) are commented upon and the possible sources
      of interference with the function of the system implanted, whether medical or
      environmental or laboral, have been analyzed more in depth. The chapter ends with
      a brief discussion on the survival of patients with pacemakers.

PMID- 10944995
TI  - [Clinical practice guidelines of the Spanish Society of Cardiology on stable
      angina].
AB  - Stable angina pectoris is the most common clinical manifestation of chronic
      ischemic heart disease, the prognosis of which depends on many factors. The
      authors have analyzed the incidence, evolution and prognosis of this problem in
      Spain and have reviewed the methods to determine the diagnosis and degree of
      clinical severity. A careful clinical history, an electrocardiogram, and the
      evaluation of the severity of the ischemia and left ventricle systolic function
      are, in most cases, useful to determine the degree of disease severity and
      establish the prognosis. In other cases, more sophisticated or complex diagnostic
      techniques such as perfusion tests, stress echocardiography and lastly coronary
      arteriography, which is the only method currently available to study coronary
      anatomy are required to carry out an adequate study of the patient. At present,
      the therapeutic arsenal for the treatment of ischemic coronary disease is
      extensive, from both a pharmacological and revascularization point of view.
      Nonetheless it is essential to carry out aggressive therapy to control the risk
      factors. The decision as to the type of treatment required mainly depends on the
      severity of the ischemia and in the case of revascularization, on the clinical
      and anatomical factors as well as on the preferences of the patient and the
      experience and results of the medical-surgical group involved in the therapy of
      these patients.

PMID- 10944996
TI  - [Ventricular tachycardia inducible in a patient with recurrent syncope after
      Senning operation].
AB  - A 17 year old man with transposition of the great vessels who had two episodes of
      late recurrent syncope following Senning repair 2 months before hospital
      registration. One episode required basic cardiopulmonary reanimation. Holter
      monitoring documented isolated polytopic and coupled ventricular extrasystoles.
      Programmed left ventricular pacing induced polymorphous ventricular tachycardia,
      which converted to monomorphic sustained ventricular tachycardia after
      intravenous procainamide. A cardioverter defibrillator was implanted in left
      ventricle by intravenous approach. Twelve months later the patient presented an
      episode of polymorphic ventricular tachycardia and one appropriate therapy from
      the defibrillator discharge was done.

PMID- 10944997
TI  - [Heart angiosarcoma: heart magnetic resonance diagnosis].
AB  - The case of a young male with a primary cardiac angiosarcoma of the right atrium
      is reported. The patient presented with a relapsing cardiac tamponade due to
      hemopericardium, the diagnosis being made by magnetic resonance. The resection of
      the tumor did not prevent an adverse outcome, as the patient died due to
      metastatic dissemination.

PMID- 10944998
TI  - [Demonstration of accelerated growth of heart sarcoma using imaging techniques].
AB  - We report the case of a patient presenting a sarcoma of interatrial septum with
      an accelerated growth and a fulminate clinical course documented by non-invasive
      image diagnostic techniques, habitual in the cardiologic practice. The natural
      history of some cardiac malignant tumours, as aggressive as in this case,
      explains the diagnostic delay, the difficulty to establish a curative treatment
      such as surgery and/or chemotherapy/radiotherapy and the awful short-term
      prognosis.

PMID- 10944999
TI  - [Congenital dysplasia of tricuspid valve (Ebstein like) in a 73-year-old male
      with severe tricuspid insufficiency].
AB  - Multiple congenital abnormalities in the structure of the tricuspid valve have
      been described and, the majority of cases could be considered as variations of
      Ebstein's anomaly. The onset of the symptoms and the diagnosis depend on the
      severity of the valve dysfunction and the right ventricular function and size.
      The age at diagnosis ranges from birth to adulthood, but a delayed diagnosis is
      rare when tricuspid regurgitation is severe. We cite as an example the case of a
      73 year-old male classified as class I of the NYHA up to 5 months before, since
      then he developed progressive ascitis and edema on his legs. The physical
      examination suggested severe tricuspid regurgitation. We performed a transtoracic
      and transesophageal ecocardiogram that showed severe dysplasia in the tricuspid
      leaflets, severe regurgitation because of lack of adequate joining, dilatation of
      right chambers and right ventricular systolic dysfunction.

PMID- 10945000
TI  - [Clinical validity of algorithms for QT measurement].

PMID- 10945001
TI  - [Pilot study of dose intensive weekly chemotherapy followed by cisplatin plus
      etoposide with concurrent thoracic irradiation for limited-disease small-cell
      lung cancer. West Japan Thoracic Oncology Group].
AB  - It was reported from a previous randomized trial (NEJM 329: 1848, 1993) that a
      moderate increase in the initial dose of cyclophosphamide and cisplatin improves
      the survival of patients with LDSCLC. Rapid administration of several active
      agents over a short treatment period, such as the CODE regimen, is a potentially
      usefully strategy for increasing the initial dose intensity. Based on these
      findings, we conducted a pilot study of CODE (C: 25 mg/m2, day 1, weeks 1-4, O: 1
      mg/m2, day 1, weeks 2, 4, D: 40 mg/m2, day 1, weeks 1, 3, E: 80 mg/m2, days 1-3,
      weeks 1, 3) chemotherapy for the first 4 weeks followed by PE therapy (P: 80
      mg/m2, day 1, E: 100 mg/m2, days 1-3, for 3 cycles) with concurrent TRT (1.5 Gy
      bid x 30 fr., total 45 Gy) to treat LDSCLC. From June 1996 through September
      1996, 23 patients (pts) were enrolled, among whom 22 were eligible. The patients'
      characteristics were as follows: median age 65; M/F, 15/7; PS, 0/1/2,9/9/4; Stage
      II/IIIA/IIIB, 3/8/11. The relative dose intensities in the CODE phase for
      patients who received this treatment were 107% for P and 156% for E, compared
      with standard PE therapy. No treatment related death occurred in this series.
      Myelosuppression was the most frequent toxicity in both treatments. Grade 3 and 4
      leukopenia and neutropenia occurred in 73% and 86% of patients in the CODE phase,
      and in 83% and 91% in the PE phase, respectively. Thrombocytopenia occurred in
      14% of the patients in the CODE phase and in 37% in the cisplatin-etoposide
      phase. Other non-hematological toxicities were mild. There was no severe
      esophagitis or pneumonitis following radiation therapy. CR was observed in 13
      (59%) of the 22 patients, and 9 (41%) patients showed PR, giving an overall
      response rate of 100%. A median survival time has not yet been ascertained. Our
      preliminary results indicate that CODE therapy followed by PE therapy with
      concurrent TRT has very high activity with acceptable toxicities. This treatment
      regimen should be compared with PE therapy and concurrent TRT in a randomized
      trial.

PMID- 10945002
TI  - [Recent topics in chemotherapy for elderly patients with lung cancer].
AB  - With the prolongation of life expectancy in Japan, lung cancer is increasing not
      only in the elderly but also in poor-risk patients who can not undergo standard
      chemotherapy. Because survival benefits from chemotherapy are clearly expected in
      patients with small-cell lung cancer (SCLC), standard chemotherapy should be
      established for the elderly as well as for poor-risk patients with SCLC. We
      recently reported that the combination of AUC-based carboplatin and a standard
      dose of intravenous etoposide was an active and relatively nontoxic regimen for
      elderly patients with SCLC (J Clin Oncol 17: 3540-3545, 1999). Had chemotherapy
      with concurrent chest irradiation been used for patients with limited disease
      (LD), better survival might have been achieved in this study. However, Pignon et
      al. reported that combined chemoradiotherapy in elderly patients with LD-SCLC is
      a possible poor prognostic factor in their meta-analysis. A recent randomized
      controlled clinical trial has shown that vinorelbine monotherapy contributed to
      longer survival in elderly patients with advanced non-small-cell lung cancer
      (NSCLC), compared to best supportive care. Several retrospective studies have
      shown that cisplatin can be safely and effectively administered to elderly
      patients who are eligible for protocol treatment. However, there have been no
      randomized trials indicating that cisplatin-based combination chemotherapy
      improves survival in elderly patients with advanced NSCLC, compared to single
      agent chemotherapy. Similarly, the role of combined chemoradiotherapy remains
      controversial in elderly patients with locally advanced NSCLC. Thus, standard
      therapies proven to be beneficial to non-elderly patients with lung cancer have
      not always been proven to be beneficial to elderly patients. In order to solve
      these difficult problems, phase III studies are warranted in elderly or poor-risk
      patients with lung cancer. Moreover, new agents with relatively low toxicities
      recently approved in Japan should be applied in clinical trials for the elderly
      or poor-risk patients with lung cancer.

PMID- 10945003
TI  - [Combination of irinotecan hydrochloride and etoposide for treatment of
      refractory or relapsed small-cell lung cancer].
AB  - We used a combination of irinotecan and etoposide with recombinant human
      granulocyte colony-stimulating factor as a support therapy for refractory or
      relapsed small-cell lung cancer (SCLC). This combination regimen was active
      against refractory or relapsed SCLC as gauged by a response rate of 71% and a
      median survival time of 271 days. Further studies of this combination regimen in
      refractory or relapsed SCLC are warranted.

PMID- 10945004
TI  - [Clinical development of antitumor agent in Europe and USA--experience on CPT-11
      development].
AB  - Irinotecan hydrochloride (CPT-11) was approved first in Japan in January 1994,
      then in France in May 1995 and in the USA in June 1996. These approvals were
      given based on Japanese non-clinical data and the clinical data from phase I and
      II studies conducted independently in each country. It took almost 3 years in
      Japan to gain approval; however, six months were sufficient for approval in
      France and the USA. Systems are well established in Europe and the USA for
      clinical studies and the development of antitumor agents. It appears that, in
      Europe and the USA, cancer patients are well supported by society and that cancer
      chemotherapies are well understood in society as well.

PMID- 10945006
TI  - [The role of the Japan Clinical Oncology Group].
AB  - The Japan Clinical Oncology Group (JCOG), a cooperative oncology group funded by
      the government of Japan, was founded in 1989. Over the past decade, the quality
      of clinical trials in Japan has improved greatly. The purpose of the JCOG is to
      establish and to improve the standard treatment of cancer by carrying out large,
      prospective, randomized, multicenter, clinical trials. The organizations to
      conduct clinical trials, such as a data center, clinical trial review committee,
      and monitoring committee, have been developed. One of the most important roles of
      the JCOG is the establishment and development of the necessary infrastructure.
      The JCOG is the largest cooperative oncology group in Japan and is conducting
      clinical trials to establish new "state of the art" treatment. However, the
      expansion of the data center and positioning of research nurses in each institute
      are essential for further development of the JCOG and clinical trials in Japan.

PMID- 10945005
TI  - [Clinical development of new molecular targeted therapeutics for cancer therapy].
AB  - Recently much attention has been paid to clinical development of new drugs
      targeting the important molecules involved in cell growth, motility, invasion,
      metastatic formation of cancer cells and tumor angiogenesis. Among them, several
      drugs are designed to inhibit those activities, by which cancer growth and/or
      metastasis may be controlled. A major problem in developing new molecular
      targeted therapeutics is determining the optimal biological dose in Phase I
      studies. Appropriate surrogate markers should be employed to evaluate their
      therapeutic efficacy before entering the Phase III study. A future strategy to
      evaluate the efficacy of new drugs in combination with conventional anticancer
      therapy (surgery, radiotherapy and chemotherapy) is required. For this, careful
      consideration must be given to the design of clinical Phase III trials. This
      paper discusses the present status and future strategy for development of new
      molecular targeted therapeutics in clinics.

PMID- 10945007
TI  - [Japan Adult Leukemia Study Group (JALSG)--twelve years of activities and future
      direction].
AB  - The JALSG was founded in 1987 as the first large scale multi-center study group
      for adult leukemia in Japan. It has grown up to be an internationally-recognized
      national group consisting of 66 institutions. Each protocol for AML has recruited
      more than 300 new cases for the study period of two years, enabling randomized
      studies. JALSG's studies have been published in international journals and
      contributed much to evidence-based medicine in Japan. For administrative
      purposes, an Internet system has been employed with a great success for case
      entry and data management. Governmental research funding for cancer research has
      been provided to the chief doctor of JALSG, enhancing its research activity
      greatly. Future JALSG studies will focus on how to improve the cure rate for
      adult leukemia by incorporating new drugs and developing new treatment
      strategies.

PMID- 10945008
TI  - [Establishment of the Japanese Radiation Oncology Study Group].
AB  - The Japanese Radiation Oncology Study Group (GROSG) which conducts multi-center
      trials, was organized in July, 1998 in order to establish standards' for
      radiation therapy. These standards must be based on the results of high quality
      trials, and the quality of radiotherapy must be assured in each hospital.

PMID- 10945009
TI  - [Infrastructure of cancer clinical trial cooperative groups in western
      countries].
AB  - Efforts for international harmonization have made it clear that Japan is far
      behind in Western countries in all aspects of infrastructure for clinical trials.
      The introduction of ICH-GCP, 1998, has promoted the rapid growth of
      infrastructure for investigational new drug (IND) trials; however, the
      infrastructure for academic cancer trials has shown no remarkable progress. There
      is still no governmental regulation, no agency for quality control, and no
      quality assurance audit system even in government-sponsored trials. The author
      introduces the quality control systems in cooperative groups in Western
      countries, such as the Southwest Oncology Group (SWOG), National Surgical
      Adjuvant Breast and Bowel Project (NSABP) and European Organization for Research
      and Treatment of Cancer (EORTC), and the quality assurance systems by the
      National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP). Key
      activities for quality control in cooperative groups are in-house monitoring,
      site visit audits, institutional performance evaluations and case report form
      review by study coordinators. NCI-CTEP oversees cooperative group activities
      through protocol review, supervision of site visit audits and a monitoring
      committee. Cancer cooperative groups in Western countries have taken the
      initiatives in advancement of trial methodology and establishment of clinical
      trial infrastructure. In order to improve the quality of clinical trials, there
      is need to invest cancer cooperative groups, thus strengthening the activities
      for overall clinical trials.

PMID- 10945010
TI  - [The role of daunorubicin in induction therapy for adult acute myeloid leukemia].
AB  - The relationship between the total dose of daunorubicin (DNR) in induction
      therapy and the treatment outcome were evaluated based upon individualized doses
      of DNR during induction therapy for patients with acute myeloid leukemia(AML).
      Ninety-two previously untreated adult AML patients admitted to our hospital were
      analyzed for the dose of DNR required for complete remission (CR), the CR rate,
      disease-free survival (DFS) and overall survival (OS). The induction therapy
      consisted of DNR (40 mg/m2/d, i.v., from D 1 until the marrow was hypoplastic),
      Ara-C, prednisolone, and/or 6-thioguanine. Eighty-three out of 92 patients were
      assessable. Sixty-three patients entered CR (76%), of whom 52 attained CR with
      the first course of induction therapy. The 10-year DFS and OS rates were 31.2%
      and 42.3%, respectively. The median total dose of DNR in the induction therapy
      was 280 mg/m2 (120-480 mg/m2), which was not influenced by initial WBC count, or
      FAB type. These results indicate that when the dose is linked to the observed
      tumor response, the optimal dose of DNR in the induction therapy is around 280
      mg/m2 (40 mg/m2 x 7 times), which is higher than the conventional dose of 40-60
      mg/m2 for 3 days. The higher dose of DNR in the induction therapy for adult AML
      should be selected when the feasibility of a new drug is evaluated in a
      randomized trial.

PMID- 10945011
TI  - [Effect of etoposide added to individualized induction therapy of adult acute
      myeloid leukemia--the JALSG-AML-92 Study. Japan Adult Leukemia Study Group].
AB  - A multicenter prospective randomized study was undertaken to assess the efficacy
      of etoposide added to the standard remission induction therapy for acute myeloid
      leukemia (AML). Consecutively registered newly diagnosed adult AML patients were
      randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl
      cytarabine (200 mg/m2/day x 10 or more) and 6-mercaptopurine (70 mg/m2/day x 10
      or more) (BH-AC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5)
      (BH-AC-EDM) for response-oriented individualized induction therapy. The patients
      achieving complete remission (CR) received the same 3 courses of consolidation
      therapy followed by 6 courses of maintenance/intensification therapy. M3 was
      excluded and M0 was included. Of 667 patients registered, 655 were evaluable. The
      median age was 49 years (range, 15 to 85). CR rates were 77% in the BH-AC-DM
      group and 75% in the BH-AC-EDM group. In M4 patients, CR rates were 86% and 69%
      (p = 0.009), and, in M5, 80% and 77% (p = 0.810) in the BH-AC-DM and BH-AC-EDM
      groups, respectively. The predicted 6-year overall survival rates were 30% and
      38% for BH-AC-DM and BH-AC-EDM groups, and the disease-free survival (DFS) rates
      of CR patients were 25% and 35% (p = 0.925), respectively. In conclusion, the
      present study failed to show any advantage of the addition of etoposide to the
      standard individualized induction therapy in adult AML, even among M4 and M5.
      These above data have already been published in the Int J Hematol (70: 87-104,
      1999).

PMID- 10945012
TI  - [Treatment of acute promyelocytic leukemia with all-trans retinoic acid and
      chemotherapy--multicenter trial of the Japan Adult Leukemia Study Group (JALSG)].
AB  - We report herein the clinical results of a multicenter trial of the Japan Adult
      Leukemia Study Group for cases of newly diagnosed acute promyelocytic leukemia
      (APL) treated with all-trans retinoic acid and chemotherapy (JALSG AML-92 study).
      Of 196 evaluable patients, 173 (88%) achieved complete remission (CR).
      Multivariate analysis showed that no or minor purpura at diagnosis and age less
      than 30 years were favorable factors for achievement of CR. There was a
      significant difference in the 4-year event-free survival between the AML-92 study
      (54%) and both the AML-87 (32%) and AML-89 (32%) studies which consisted of
      intensive chemotherapy. Since prognosis in patients with APL largely depends on
      chemotherapy, it is important to consider more effective chemotherapy during
      induction and consolidation therapy.

PMID- 10945013
TI  - [Concurrent chemoradiotherapy for T4 and/or M1 LYM squamous cell carcinoma of the
      esophagus].
AB  - A phase II study was conducted to investigate the efficacy and feasibility of
      chemoradiotherapy for locally advanced carcinoma of the esophagus. Fifty-four
      patients with clinical T4 and/or M1 LYM squamous cell carcinoma of the esophagus
      were enrolled. Patients received protracted infusions of fluorouracil 400
      mg/m2/24 hours on days 1 to 5 and 8 to 12, 2-hour infusions of cisplatin 40 mg/m2
      on days 1 and 8, and concurrent radiotherapy at a dose of 30 Gy in 15 fractions
      over 3 weeks. Filgrastim was prophylactically administered to 35 patients. This
      schedule was repeated twice every 5 weeks, for a total radiation dose of 60 Gy
      followed by two courses of fluorouracil (800 mg/m2/24 hours for 5 days) and
      cisplatin (80 mg/m2 on day 1). There were 36 patients with T4 disease and 33 with
      M1 LYM. Forty-nine patients (91%) completed the chemoradiotherapy segment. The 18
      patients (33%) who achieved a complete response included nine (25%) of the 36
      with T4 disease and nine (50%) of the 18 with non-T4 disease. Major toxicities
      were leukopenia and esophagitis; there were four (7%) treatment-related deaths.
      Prophylactic filgrastim reduced the incidence of grade 3 or worse leukopenia
      without improving dose-intensity or response. With a median follow-up duration of
      43 months, median survival time was 9 months. The 3-year survival rate was 23%.
      Despite its significant toxicity, this combined modality seemed to have curative
      potential even in cases of locally advanced carcinoma of the esophagus.

PMID- 10945014
TI  - [Combination chemotherapy with vinorelbine and other cytotoxic agents for
      advanced breast cancer patients--a protocol of vinorelbine plus AC regimens used
      by the Japan Vinorelbin Study Group].
AB  - A new generation type of vinca alkaloid, vinorelbine (VNR), is a promising agent
      for the treatment of breast cancer patients. As a first line treatment for
      metastatic breast cancer, combination chemotherapy including anthracyclines plus
      VNR has demonstrated a high response rate and tolerability. In addition, other
      VNR containing regimens, such as 5-fluorouracil plus VNR, produced a 64% response
      rate. This evidence suggests VNR-containing combination chemotherapy may be a
      promising first-line treatment for breast cancer patients. In Japan, VNR is not
      registered, but a late phase II study has been completed. An approximately 30%
      response rate was obtained with its use as a monotherapy. In addition, a phase
      I/II study of combination VNR plus AC (adriamycin + cyclophosphamide) has been
      conducted. At the present time, the results are being analyzed.

PMID- 10945015
TI  - [Interventional trial for colorectal cancer prevention in Osaka].
AB  - We established a protocol for an interventional randomized controlled trial for
      the prevention of colorectal tumors, in which special importance was attached to
      practicality. The subjects are patients with multiple colorectal tumors, who form
      a high risk group for colorectal cancer. Two regimens were formulated for the
      prevention of colorectal cancer. One was dietary guidance alone (Regimen I), and
      the other was dietary guidance plus the ingestion of wheat bran biscuits (Regimen
      II). One of the two regimens is assigned at random each week in advance, and the
      patients are recruited to receive the regimen of the week in which they are first
      examined, after giving informed consent. The dietary guidance aims to restrict
      the energy intake of oil and fat to 18-22% of the total energy intake. Biscuits
      with a wheat bran content of 30% by weight, which we developed, were prescribed
      at 25 g/day (7.5 g/day as wheat bran). The main end points of the trial were
      examinations for recurrence of colorectal tumors after 4 years. The target number
      of patients is 200 in total, i.e., 100 for each group. The recruiting of subjects
      was started in June, 1993, and finished in September, 1997; 100 (90%) of 115
      patients recruited for Regimen I and 100 (88%) of 116 patients recruited for
      Regimen II consented to participate in the trial. No severe adverse effects have
      been reported, and the trial is progressing well. The trial will be completed in
      September, 2001, when the 4-year follow-up of the last patient will end.

PMID- 10945016
TI  - [Tumor microcirculation and selective enhancement of drug delivery--clinical
      applications based on pathophysiological experiments].
AB  - Tumor tissue is composed of cancer cells (parenchyma) and tumor vessels
      (interstitium). Many investigators have pointed out that blood flow in tumors has
      a very inhomogenous distribution, and that this inhomogeneity in blood flow
      increases as tumors grew. This would be a certain cause of insufficient drug
      delivery to tumor tissues. Among the experimental evidence using Yoshida Sarcoma
      and Ascites Hepatomas, functional differences in microcirculation between tumor
      and normal tissues were found by Suzuki et al. (1977). Under hypertensive state
      induced by the continuous infusion of angiotensin II, tumor blood flow increased
      remarkably, while there was no change or decrease in blood flow in normal tissues
      such as the brain, bone marrow, liver and kidney. Moreover, the increase in blood
      flow in tumors was selective, as the mean blood pressure remained at the level of
      150 mmHg. Increases were confirmed not only in many growing sites such as in the
      liver, muscle, subcutis, and even microfoci, but also in various kinds of
      xenografted human tumors and autochthonous tumors. Augmentation of the anti-tumor
      effects of angiotensin II-induced hypertension chemotherapy (IHC) for advanced
      gastric carcinoma was revealed in two randomized controlled trials (RCT-1 & 2) of
      collaborative study groups in Japan. The response rates were 42.9% vs 10.5% in
      RCT-1 and 31.3% vs 6.7% in RCT-2. The frequencies of toxicities were not
      statistically different. In the results of phase II studies from 1978 to 1994
      (OPN-1) and 1995 to 1999 (OPN-2) for advanced gastric carcinoma (GC), the
      response rates were 37.9% and 35.7%. Down staging in which the conclusive stage
      score was lower than the score of the clinical stage, was observed in 8 out of 94
      cases (19%) with primary lesions in total and in 30 patients (63%) receiving
      reduction surgery after IHC, since 1978. It is very important for exact
      evaluation after chemotherapy to understand or estimate the pathohistological
      changes in the tumor and its degenerated or repaired tissues, which present
      various clinical images. In the present study, the actual administered dose
      intensity of adriamycin (aDIadm) was 5.9 +/- 2.4 mg/sqm/w, and the ratio of
      aDIadm to the proposed DIadm of reported FAM/FAP schedules was 0.78 +/- 0.32. IHC
      with smaller DI could lead to a reduction in the accumulation of toxicities of
      anti-cancer drugs in the host. In conclusion, IHC might be applied to all kinds
      of tumors to enhance the chemotherapeutic effects through selective increase of
      drug delivery to tumors.

PMID- 10945017
TI  - [Clinical quality assurance at institutions according to a patterns of care
      study. Japanese PCS Working Group].
AB  - The clinical quality assurance (QA) of an institution is important in any
      multiinstitutional prospective study. Patterns of Care Study (PCS) is a well
      known study for QA activity in the United States. PCS is a nationwide
      retrospective study done by two-staged cluster sampling of institutions and
      patients and external audits. After data are accumulated, National averages on
      various survey items are calculated as a QA measure. In 1996, PCS was imported
      into the radiation oncology field in Japan with the support of the Ministry of
      Health and Welfare. Preliminary results showed significant differences in
      treatment process, structure, and preliminary outcome according to the
      stratification of institutions. These data can be useful in improving the
      structure and process at the institutional as well as the national level. PCS
      will also clarify the dissemination of positive clinical results into national
      practice.

PMID- 10945018
TI  - [Thymidine phosphorylase and angiogenesis].
AB  - Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell
      growth factor (PD-ECGF). TP has an angiogenic activity and confers resistance to
      hypoxia-induced apoptosis on cells. TP expression is correlated with microvessel
      count, invasion and poor prognosis in many solid tumors. TPI, an inhibitor of TP,
      suppresses growth and metastasis of tumors by inhibiting the effect of TP.

PMID- 10945020
TI  - [Recombinant adenovirus expressing wild-type p53 is antiagiogenic--implication
      for lung cancer gene therapy].
AB  - Angiogenesis is required for the growth and progression of malignancies. Recent
      studies have demonstrated that genetic alterations may accompany acquisition of
      the angiogenic phenotype. Here we demonstrate that the recombinant adenovirus
      mediated transfer of the wild-type p53 gene into a mutant p53-expressing human
      non-small cell lung cancer cell line markedly inhibited the expression of an
      angiogenic factor, vascular endothelial growth factor (VEGF), and increased the
      expression of a novel antiangiogenic factor, brain-specific angiogenesis
      inhibitor 1 (BAI 1), resulting in reduced neovascularization in vivo. These
      results may explain in part the mechanism of the bystander effect induced by wild
      type p53 gene transfer of adjacent tumor cells.

PMID- 10945019
TI  - [Antiangiogenesis therapy and hormone therapy--their resemblance and applications
      of prognostic and predictive factors].
AB  - Many new ideas to control tumor angiogenesis are now being tested in clinical
      trials. In considering strategies for clinical development of antiangiogenesis
      treatment, that of endocrine therapy might be particularly useful as a model.
      Endocrine therapy is a unique treatment used only for hormone-dependent tumors;
      however, its clinical fruits are exceptional in the entire history of cancer
      therapy. It is now clearly proven that long-term continuous treatment with
      antihormones brings a magnificent survival benefit for primary breast cancer
      patients. This benefit is tumor-phenotype oriented, where the hormone receptor is
      characterized as a potent predictive factor. Antiangiogenesis treatments seem to
      have several similarities with endocrine therapy, in that both treatments are
      cytostatic, stroma-targeting, time-dependent and less effective for large tumor
      burdens. A combination effect with chemotherapy is often observed with both
      treatments, at least in animal experiments. In a sense, anti-oncogene product
      therapy follows endocrine therapy in clinical development. Although
      antiangiogenesis treatments should be developed based on original concepts, the
      successful experience of endocrine therapy may provide many hints for the
      development of antiangiogenesis therapy.

PMID- 10945021
TI  - [Chemo/endocrine therapy for breast cancer patients].
AB  - Standard adjuvant chemo/endocrine therapy for breast cancer patient is based upon
      St. Gallen's consensus 1998. Recent development in the field of adjuvant
      chemo/endocrine therapy is an usage of LH-RH analogue with tamoxifen for
      premenopausal hormone receptor positive women, and also an emerging role of
      taxans. Orally given 5-FU derivatives may work in adjuvant settings. The third
      generation aromatase inhibitors have established their role in second line
      hormone therapy for the advanced or recurrent breast cancer patients. High dose
      chemotherapy should not be used in outside clinical trials.

PMID- 10945022
TI  - [State of the treatment for gastrointestinal cancer].
AB  - We reviewed the results of chemotherapy for gastrointestinal cancer. In Western
      countries, FAMTX or ECF is recognized as the standard therapy for gastric cancer.
      In Japan, no standard chemotherapeutic regimen has been established yet, but FP
      or MTX/5-FU are often used as a first line chemotherapy. There have been only a
      few clinical trials of adjuvant chemotherapy for gastric cancer in which this
      regimen was identified as having a statistically significant effect. For colon
      cancer, 5-FU plus LV are now used as the standard therapy. Recently, however, it
      has been shown that 5-FU + LV combined with CPT-11 is more active than 5-FU + LV
      alone. The efficacy of oral anticancer agents such as UFT + LV, S-1, and
      capecitabin have also been shown to be equally or more active than i.v.
      administration of 5-FU and LV, so that the standard therapy for colon cancer will
      be changed in near future.

PMID- 10945023
TI  - [Treatment of lung cancer--state of the art in 2000].
AB  - Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer
      chemotherapy and radiotherapy. Standard therapies for extensive SCLC are
      combination chemotherapies with cyclophosphamide, adriamycin and vincristine
      (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE
      program. On the other hand, the standard therapy for limited SCLC is
      chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated
      radiotherapy. Based on the therapy, the current state of treatment of small cell
      lung disease is a median survival time of 10 months and a 3-year survival in 10%
      of patients with extensive disease, and a median survival time of 30 months and a
      3-year survival in 30% of patients with limited disease. Promising trials under
      investigation including those for dose-intensive chemotherapy, multimodality
      treatment and combination chemotherapy adopting new drugs are introduced. The
      standard therapy for inoperable stage III non-small cell lung cancer is a
      multimodality therapy employing chemotherapy and radiotherapy. However, neither
      the timing of the radiotherapy nor the optimal combination of anti-cancer agents
      has yet been established. Nowadays, the combination of cisplatin-based
      chemotherapy and radiotherapy is expected to bring a median survival time of 15
      months and a 3-year survival in 25% of patients. For stage IV non-small cell lung
      cancer, chemotherapy prolongs survival time by a modest but statistically
      significant amount of time. For the treatment of inoperable lung cancer, the
      survival benefit from the use of newly developed drugs with or without platinum
      is under investigation.

PMID- 10945024
TI  - [Mechanism of resistance to growth inhibition by transforming growth factor-beta
      1 (TGF-beta 1) in primary lung cancer and new molecular targets in therapy].
AB  - Transforming Growth Factor-beta 1 (TGF-beta 1) regulates the proliferation of
      normal epithelial cells, and resistance to TGF-beta 1 growth inhibition is a
      common feature of human cancers including lung cancer. In order to understand the
      mechanism of resistance to growth inhibition by TGF-beta 1 and to reverse the
      regulation of proliferation in lung cancer, we determined the genomic structure
      of the genes involved in the signal transduction pathway of TGF-beta 1 and
      performed an initial mutation survey of the complete coding region of the genes
      in lung cancer and cell lines with the resistance to growth inhibition by TGF
      beta 1. First, a mutation analysis of the TGF-beta type II receptor (TGF-beta
      RII) was performed. Point mutations of the gene were detected in several colon
      cancers and an adenocarcinoma of the lung in the poly-A sequence. No mutations of
      Smad 2, 3, 4, 5 and TGF-beta type I receptor (TGF-beta IR) genes were detected in
      a series of the tumors we tested, although several mutations of Smad 2 and 4 were
      previously reported. Frequent alterations of the p15 gene and reduced expression
      of p21 we already reported from our previous studies. We also determined the
      genomic structure of the mannose 6-phosphate/insulin-like growth factor 2
      receptor (M6P/IGF2R), which is involved in activating TGF-beta 1, and performed
      an initial mutation survey of the complete coding sequences of the gene. A point
      mutation at exon 40 was found in one lung adenocarcinoma cell line. In summary,
      alterations in the many genes involved in the signal transduction of TGF-beta 1
      were found and may mediate the loss of TGF-beta 1 responsiveness in lung cancer.
      The molecular targets for the regulation of the proliferation of lung cancer are
      thought to be p15, p21 and the transcriptional regulators.

PMID- 10945025
TI  - [Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21].
AB  - Five human cancer cell lines (MKN 45, HT-29, WiDr, PAN-3-JCK, and CRL 1420) were
      used to evaluate the antitumor spectrum of UCN-01, which suppressed the growth of
      these digestive cancer cell lines. A human pancreatic cancer xenograft (CRL 1420)
      and breast cancer xenograft (MX-1) were used to determine their sensitivity to
      UCN-01, in nude mice. UCN-01 significantly suppressed the tumor growth of CRL
      1420 at a dose of 10 mg/kg in a schedule of (qd x 5) x 2, but was ineffective for
      MX-1. While p21 protein expression was induced by UCN-01 in both CRL 1420 and MX
      1, an accumulation of dephosphorylated ppRb was observed only in CRL 1420,
      resulting in G1 block as detected by flow cytometric analysis. The CDK 2 activity
      of MX-1 was almost 6 times higher than that of CRL 1420, which might account for
      the resistance of MX-1 to UCN-01 in spite of the induction of p21 in this strain.
      We conclude that the determinant of sensitivity to UCN-01 lies in the balance of
      CDK 2 kinase activity and p21 protein induction.

PMID- 10945026
TI  - [CPT-11 (irinotecan)--evidence from molecular and pharmacological studies and
      clinical applications].
AB  - Irinotecan (CPT-11) is a derivative of the chemotherapeutic agent Camptothecin.
      CPT-11 inhibits the nuclear enzyme topoisomerase I. It has demonstrated a broad
      spectrum of antitumor activity in preclinical tumor model systems. Significant
      advances have been made toward the understanding of the pharmacokinetics and
      schedule dependency of this agent. The principal dose limiting toxicities are
      diarrhea and leukopenia. CPT-11 has been evaluated using a variety of dosing
      schedules. Two main schedules have been studied and produce similar activity and
      side-effects: the "Japanese-North American" one where CPT-11 is given at a weekly
      dose of 100-150 mg/m2 for 4 consecutive weeks followed by a 2 week rest period,
      and the "European" one-350 mg/m2 every 21 days. CPT-11 has demonstrated
      significant clinical activity in the treatment of patients with gastrointestinal,
      pulmonary, gynecologic, and lymphoid malignancies. A recent randomized trial
      demonstrated a survival advantage in metastatic non-small cell lung cancer and
      previously untreated metastatic colorectal cancer. Further study of this agent to
      determine its role in combination chemotherapeutic regimens is currently
      underway.

PMID- 10945027
TI  - [Evidenced-based medicine and future direction of Taxol].
AB  - Taxol was introduced for the clinical treatment of several solid tumor
      malignancies in the 1990s. It has been established that primary chemotherapy
      based on Taxol is the standard for non-small cell lung cancer and epithelial
      ovarian cancer. After initial chemotherapy containing doxorubicin, sequential
      administration of Taxol for advanced or metastatic breast cancer is recommended
      by the Food and Drug Administration in the United States. Taxol-based
      chemotherapy and/or concurrent chemoradiation for head and neck cancer,
      esophageal carcinoma, urothelial and prostate cancer are under investigation, but
      these trials have not produced evidence showing that they are superior to the
      present standard treatment for these malignancies. Although phase I/II trials of
      Taxol combined with new agents such as vinorelbine, topotecan, CPT-11 and others
      may demonstrate efficacy to a certain extent for some solid tumor malignancies, a
      phase III study will be required in the next stage. Taxol combined with other
      agents focusing on molecular targets will be an important approach in next
      decade. Inhibition of signal transduction by a noncytotoxic agent such as
      herceptine has the potential to enhance the cytotoxic effect of Taxo.

PMID- 10945028
TI  - [Evidence for Taxotere treatment with solid tumors].
AB  - Evidence based medicine is essential to further develop the state of the art for
      cancer treatments. We introduce the levels of evidence for Taxotere treatment
      against various solid tumors. Most evidence for Taxotere therapy was produced in
      other countries. However, in Japan we have some data from phase II clinical
      trials for the approval of Taxotere. We review these domestic results, which
      reveal its usefulness and toxicity in Japanese patients. In addition, we analyze
      the evidence from the data of clinical trials of Taxotere conducted by
      investigators in the USA/Europe. Japanese physicians or academies must build a
      consensus for the application of Taxotere to Japanese patients with solid tumors.

PMID- 10945029
TI  - [Current status and future directions of gemcitabine in the treatment of non
      small cell lung cancer and pancreatic cancer].
AB  - New agents with high anti-tumor effects have been developed since 1990.
      Monotherapy with one of these agents, gemcitabine, was confirmed to be as
      effective as the standard chemotherapy regimen against NSCLC, and to have a lower
      toxicity profile. In addition, the combination of gemcitabine plus cisplatin can
      be expected to show a survival advantage. The combination therapy consisting of
      these two new anti-cancer agents is expected to show effectiveness equal to that
      of platinum-based combination chemotherapy. Gemcitabine is well tolerated, so
      that it can be a useful treatment for maintaining QOL among the elderly or in
      poor performance status patients with NSCLC. Considering that this agent is also
      effective against pancreatic cancer, further investigation for efficacy against
      other cancers is warranted.

PMID- 10945030
TI  - [Vinorelbine in the treatment of non-small-cell lung cancer and breast cancer].
AB  - Vinorelbine is a new semisynthetic vinca alkaloid with significantly less
      neurotoxicity than other vinca alkaloids. It was recently approved by the
      Ministry of Health and Welfare in Japan for the treatment of non-small-cell lung
      cancer. Vinorelbine is active in metastatic breast cancer with a first time
      response rate of 40% to 52%. High response rates were observed with combination
      chemotherapies of vinorelbine and other active agents for breast cancer. In non
      small-cell lung cancer, four randomized phase III trials of vinorelbine
      demonstrated that vinorelbine alone, or combination chemotherapy of vinorelbine
      with cisplatin, improved survival more than best supportive care or cisplatin
      plus vindesine, respectively. There is a high level of evidence that vinorelbine
      is an effective agent for the treatment of non-small-cell lung cancer.

PMID- 10945031
TI  - [Capecitabine--a review of its antitumor activity and toxicity in clinical
      studies].
AB  - Capecitabine is a novel fluoropyrimidine carbamate, orally administered and
      rationally designed to undergo tumor-selective activation. Some studies have been
      proven it to be safe for outpatient treatment and to have significant antitumor
      activity in colorectal and breast cancer patients. Randomized trials of patients
      with advanced colorectal cancer using capecitabine versus Leucovorin (LV).5-FU
      were studied in two groups. Capecitabine results in both a higher response rate
      and a more favorable toxicity profile than LV.5-FU. In women aged 55 years or
      more with breast cancer, capecitabine showed at least comparable efficacy to CMF
      combination therapy. Capecitabine offers a new effective oral treatment option as
      a single agent for patients with advanced colorectal or breast cancer.

PMID- 10945032
TI  - Fibroblast heterogeneity in physiological conditions and fibrotic disease.
AB  - Inflammation and tissue injury are strong stimuli for fibroblast activation and
      initiation of reparative processes. In certain disease states, pathological
      fibrosis occurs. Fibroblasts isolated from these diseased tissues often display a
      persistently abnormal phenotype characterized by increased synthesis of matrix
      components such as collagen. This metabolic abnormality is apparently independent
      of continued exposure to any pathological stimulus that may have initiated the
      process. Since fibroblasts are heterogeneous in proliferative capacity, in
      synthesis of collagen and other matrix proteins and in response to immune
      mediators and growth factors, clonal selection, i.e. selective increase in
      fibroblast subpopulations, may explain the long-term effects of acute in vivo
      activation on fibroblast behavior. Studies of SSc fibroblasts are consistent with
      clonal selection and/or clonal activation, processes that may play an important
      role in fibrosis in this and other disorders.

PMID- 10945033
TI  - Alterations in the regulation of expression of the alpha 1(I) collagen gene
      (COL1A1) in systemic sclerosis (scleroderma).
AB  - At present, the mechanisms that regulate the expression of collagen genes in
      normal and pathologic fibroblasts are not known. Thus, the detailed study of
      transcriptional regulation of COL1A1 in SSc cells will increase our current
      understanding of the pathophysiology of fibrotic diseases. These studies will
      yield valuable information regarding the important biological process of
      regulation of collagen gene expression under normal and pathologic conditions, a
      process that has remained elusive despite intense recent investigations. It is
      now evident that persistent overproduction of collagen is responsible for the
      progressive nature of tissue fibrosis in SSc. Up-regulation of collagen gene
      expression in SSc fibroblasts appears to be a critical event in this process. The
      coordinate transcriptional activation of numerous collagen genes suggests a
      fundamental alteration in the regulatory control of gene expression in SSc
      fibroblasts. Trans-acting nuclear factors which bind to cis-acting elements in
      enhancer (intronic) and promoter regions of the genes modulate the basal and
      inducible transcriptional activity of the collagen genes. The identification of
      the nuclear transcription factors that regulate normal collagen gene expression
      may provide promising approaches to the therapy of this incurable disease.

PMID- 10945034
TI  - Interactions of fibroblasts with the extracellular matrix: implications for the
      understanding of fibrosis.
AB  - The cellular organization and the compartmentalization in multicellular organisms
      is mediated by the extracellular matrix (ECM). This structure is composed by a
      wide variety of different macromolecules which carry distinct domains with
      defined structural and/or biological activities. Cells are known to interact with
      these molecules via specific receptors. Following activation, these receptors
      transduce signals either directly to the intracellular cytoskeleton or via
      different signalling cascades. Cell-matrix interactions, therefore, not only
      control the shape and orientation of cells but can also directly regulate
      cellular functions, including migration, differentiation, proliferation, and the
      expression of different genes. These cell-matrix interactions have been
      elucidated in detail for several biological processes, especially morphogenesis
      and differentiation, but also play an important role during pathological
      situations, e.g. wound healing and tumor progression. Although much less
      investigated, similar mechanisms are thought to regulate the biological behavior
      of fibroblastic cells, the final target cells in fibrosis. The activity of these
      cells depends in various ways on the presence of ECM molecules. First, some of
      the molecules are known to bind to and modulate the activity of those growth
      factors and cytokines, which lead to the activation of fibroblasts during the
      early phases of fibrosis. Second, deposition of large amounts of ECM molecules
      alters the environment and the mechanical load on the cells which are embedded in
      this matrix. Third, ECM molecules directly modulate fibroblast metabolism via
      certain integrin receptors. This review summarizes recent developments in all
      three domains. It mainly focuses on the direct role of ECM molecules in the
      biosynthetic activity of fibroblasts.

PMID- 10945036
TI  - Lung fibrosis.

PMID- 10945035
TI  - T lymphocyte and fibroblast interactions: the case of skin involvement in
      systemic sclerosis and other examples.

PMID- 10945037
TI  - Liver fibrosis.
AB  - Knowledge on the development and progression of liver fibrosis has grown
      exponentially in the past decade. At present, liver fibrogenesis is referred to
      as a dynamic process involving complex cellular and molecular mechanisms,
      resulting from the chronic activation of the tissue repair mechanisms that
      follows reiterated liver tissue injury. The identification and characterization
      of the cell types and of the different mediators involved in this process has
      allowed a "re-visitation" of several issues related to liver cirrhosis and its
      immediate consequences. Among these, evaluation of the relationships occurring
      between fibrogenesis and portal hypertension, cholestasis and the development of
      hepatocellular carcinoma, represent some of the hottest areas of research in this
      field of hepatology. The elucidation of many of the cellular and molecular
      mechanisms responsible for the progression of liver fibrosis has provided a sound
      basis for the development of pharmacological strategies able to modulate this
      important pathophysiological process.

PMID- 10945038
TI  - Myelofibrosis: pathogenesis of myelofibrosis with myeloid metaplasia. French
      INSERM Research Network on Myelofibrosis with Myeloid Metaplasia.

PMID- 10945039
TI  - A randomized, parallel-group study in Mumbai (Bombay), comparing chloroquine with
      chloroquine plus sulfadoxine-pyrimethamine in the treatment of adults with acute,
      uncomplicated, Plasmodium falciparum malaria.
AB  - A major problem in the control of malaria is the development of resistance, of
      the parasites to the existing drugs and of the vectors to insecticides. With few
      new drugs in the pipeline, in an era of declining resources, it is imperative to
      make judicious use of the existing antimalarials. In the city of Mumbai,
      resistance exists to chloroquine (CQ) and to sulfadoxine-pyrimethamine (SP). Use
      of a combination of CQ with SP would theoretically slow down the development of
      resistance to each of the drugs and increase their useful lives. The
      effectiveness of this combination in the treatment of adults from Mumbai, who had
      acute, uncomplicated Plasmodium falciparum malaria, was compared with that of CQ
      alone. The combination was found to be significantly more effective, in terms of
      28- or 42-day cure rates, and to be more cost-effective.

PMID- 10945040
TI  - Mefloquine-resistant strains of Plasmodium falciparum in Madagascar: impact on
      tourists and public health.
AB  - Although the national policy for malaria control in Madagascar is to use
      chloroquine as the first line of treatment, mefloquine has been and is
      recommended to travellers to the country, both for malaria prevention and cure.
      The in-vitro susceptibility of Plasmodium falciparum to mefloquine was therefore
      assessed during a prospective surveillance study in various areas in Madagascar,
      including the tourist sites of Nosy-be and Sainte Marie. Of the 254 isolates of
      P. falciparum successfully tested, 232 (90.9%) were sensitive to mefloquine, 12
      (4.7%) showed decreased susceptibility (40 nM < IC50 < 50 nM), and 10 (3.9%) were
      resistant (IC50 > 50 nM). Five (50%) of the resistant strains and nine (75%) of
      those with decreased susceptibility were from coastal areas or the two tourist
      sites. The drug pressure that could have induced the resistance observed could
      therefore be related to the donation of antimalarials, such as mefloquine, by
      tourists to local populations. The residents of the coastal areas take any
      donated drugs as self-medication, ignoring recommended doses and durations of
      treatment. This situation has two main consequences: (1) there is an urgent need
      to control the abusive and incorrect use of antimalarial drugs in Madagascar, to
      safeguard the effectiveness of chemotherapy in the future; and (2) these
      increases in resistance compromise the efficiency of the antimalarial
      chemoprophylaxis currently recommended to tourists. The use of mefloquine can no
      longer be considered as a guarantee of protection against malaria in coastal
      areas and other sites frequented by tourists.

PMID- 10945041
TI  - IgG-subclass antibody responses and the natural history of hepatic cystic
      echinococcosis in asymptomatic patients.
AB  - Given that cystic echinococcosis (CE) is a serious clinical problem in endemic
      countries, there is still relatively little information available on the natural
      history of the human disease. The aim of the present study was to correlate
      serological status with pathology, in ultrasound-characterised, asymptomatic
      cases of human CE. Serum concentrations of IgG reacting with antigen B from cyst
      fluid and of similarly specific IgG1, IgG2, IgG3 and IgG4 were determined by
      ELISA and further investigated by immunoblotting. CE cases with simple cysts
      (Type I), or cysts with clear laminations and daughter cysts (Types II and III)
      exhibited elevated IgG4 seropositivity, whereas concentrations of specific IgG1
      and IgG4 declined in CE cases characterised by cyst infiltration or
      calcifications (Types IV and V). The responses of each specific IgG subclass were
      used, in association with an ultrasound classification, to try to develop an
      immunoserological natural-history profile of CE in asymptomatic patients.
      Specific IgG4 antibody responses were particularly associated with the evolutive
      phase of CE (Types I, II and III), whereas the IgG1, IgG2 and IgG3 responses
      tended to be associated with the involutive phase (Types IV and V). These results
      indicated that an IgG4 antibody response was associated with (or was a marker
      for) cystic development, growth and disease progression, whereas the IgG1, IgG2
      and IgG3 responses occurred predominantly when cysts became infiltrated or were
      destroyed by the host. The findings support the view that evolutive and
      subsequent involutive phases occur in untreated CE.

PMID- 10945042
TI  - Echinococcosis in the stray dogs of Tehran, Iran.
AB  - Echinococcus granulosus infections were detected in 29 (48%) of 60 stray dogs
      from Tehran. The adult worms, in a random sample, measured 3.0-7.7 mm in length.
      The mean, estimated age of the dogs investigated was 5 years, with no significant
      differences in the prevalences observed in the young, mature and old animals. Bad
      abattoirs and the frequent slaughter of animals in places other than abattoirs
      appear to be the main reasons for the high prevalence of canine echinococcosis in
      Tehran and elsewhere in Iran.

PMID- 10945043
TI  - Possible effects of the Three Gorges dam on the transmission of Schistosoma
      japonicum on the Jiang Han plain, China.
AB  - The Three Gorges dam, under construction on the Yangtze River in China, might
      affect the transmission of Schistosoma japonicum on the Jiang Han plain, which is
      downstream of the dam. To study this possibility, the prevalence of
      schistosomiasis was investigated in relation to a range of malacological,
      hydrological and meteorological factors. The general water level in the Yangzte
      over a year had a marked effect on the distribution of the intermediate host
      (Oncomelania hupensis) and the prevalence of human schistosomiasis in that year.
      Disease prevalence showed significant correlations with the density of the snail
      hosts, the level of the water table, annual rainfall, yearly evaporation, and
      altitude. Once the dam is complete, the flow of water downstream will probably be
      maintained at a level between those currently occurring in flood and dry weather,
      and this may have implications for schistosome transmission. Systematic
      monitoring is necessary to investigate the impact of the environmental changes
      brought about by the dam on transmission.

PMID- 10945044
TI  - Controlling onchocerciasis by community-directed, ivermectin-treatment programmes
      in Uganda: why do some communities succeed and others fail?
AB  - In Uganda, human onchocerciasis is controlled by annual, mass, community
      directed, ivermectin-treatment programmes (CDITP) in all endemic communities
      where the prevalence of the disease is > or = 30%. This is a practical, long-term
      and cost-effective strategy. In some communities, this system succeeds in
      providing treatment at the desired level of coverage (i.e. 90% of the annual
      treatment objective, which is itself equivalent to all those individuals eligible
      to take ivermectin). Other communities, however, fail to reach this target. The
      aim of the present study was to determine the factors that were significantly
      associated with success or failure in achieving this target. The data analysed
      were answers to a questionnaire completed by 10 household heads randomly selected
      from each of 64 randomly selected endemic communities (of which 36 succeeded and
      28 failed to reach their coverage target) in the four districts of Kabale, Moyo,
      Nebbi and Rukungiri. Among the programme-related factors investigated, success
      was associated, at a statistical level of significance (P < or = 0.05), with
      involvement of community members in: (1) decisions about the execution of the
      programme; (2) attendance at health-education sessions; (3) selection of the
      community-based distributors (CDB); and (4) rewarding CBD in kind. In general,
      the involvement of community members in the planning and execution of a CDITP
      (and the resultant sense of pride in community ownership) was more likely to
      produce successful results than when external health workers or even community
      leaders or local councils took responsibility.

PMID- 10945045
TI  - The impact of lymphatic filariasis on labour inputs in southern India: results of
      a multi-site study.
AB  - A multi-site study was undertaken, in the rural areas of three districts in Tamil
      Nadu state, in southern India, to examine the impact of acute and chronic forms
      of lymphatic filariasis, caused by infection with Wuchereria bancrofti, on labour
      inputs. More than half of the acute episodes of adenolymphangitis (ADL) observed
      in the study communities caused total disability. The mean (S.D.) time that each
      ADL case was able to allocate to economic activity each day during these acute
      episodes was much less than seen in the controls matched for sex, age and
      occupation [0.97 (2.36) v. 4.48 (3.82) h; P < 0.01]. The acute disease also
      severely affected domestic activities, with female ADL cases spending only 1.54
      (2.12) h/day on domestic activity, compared with 4.18 (2.61) h by controls. The
      subjects with chronic filariasis also spent significantly less time in economic
      activity than their matched controls [4.40 (3.79) v. 5.13 (3.83) h/day; P <
      0.01). Although the acute episodes have a dramatic effect on the productivity of
      the affected individual, the labour loss caused by chronic disease is more
      serious, as the manifestations of chronic disease mostly affect the most
      productive age-groups, persist for life and are mostly irreversible. The adverse
      impact of acute and chronic filariasis was observed in males and females, farmers
      and non-farmers and during the rainy, winter and summer seasons. It is estimated
      that about 3.8% of the potential labour inputs of the men and 0.77% of those of
      the women were lost because of lymphatic filariasis. In addition to this loss,
      the total economic burden of the disease must include the costs of treatment and
      other health care and of the resources spent on control programmes. Estimates of
      the disease burden are likely to be useful in determining the costs and benefits
      of the recently launched campaign to eliminate lymphatic filariasis.

PMID- 10945046
TI  - Comparative epidemiological studies on lymphatic filariasis, between tribal and
      non-tribal populations of Bankura district, West Bengal, India.
AB  - There is little information on the epidemiology of lymphatic filariasis, caused
      by infection with Wuchereria bancrofti, in West Bengal. That which is known
      mostly relates to Calcutta and its suburbs, and there have been few studies on
      the disease among the tribal populations of the state. The present study was
      designed to compare the epidemiology of filariasis in tribal and non-tribal
      populations living in Bankura district. Blood samples were collected at night
      from 2076 tribal and 4985 non-tribal subjects and checked, microscopically, for
      microfilariae (mff). Each subject was also examined clinically, for any
      manifestations of the disease. The results revealed that the tribal subjects had
      not only lower prevalences of microfilaraemia (3.17% v. 8.86%) and of symptomatic
      filariasis (5.92% v. 13.74%) than the non-tribal, but also less intense
      infections (with mean counts for the microfilaraemics of 6.50 v. 13.55 mff/20
      microliters blood). Filariasis endemicity, measured as the percentage of subjects
      with microfilaraemia and/or disease, was therefore much lower among the tribal
      subjects (8.95%) than the non-tribal (22.12%).

PMID- 10945047
TI  - The microfilarial periodicity of Wuchereria bancrofti in north-eastern Brazil.
AB  - The periodicity of Wuchereria bancrofti microfilariae (mff) in peripheral blood
      was analysed in 42 microfilaraemics living in Maceio, in Alagoas state, north
      eastern Brazil. Nine blood samples were collected from each subject, over a 24-h
      period, and two quantitative (60-microliter) thick smears were prepared from each
      sample. Although all the subjects had detectable microfilaraemias from 23.00
      hours to 06.00 hours, no mff could be detected in most (71.4%) of the smears
      prepared from samples collected at 15.00 hours. Samples collected during the day,
      at 15.00 hours, contained 170 times fewer mff/microliter than those collected at
      01.00 hours, when microfilaraemias were generally most intense. For diagnosis of
      bancroftian filariasis in Maceio, blood samples should be collected between 22.00
      and 03.00 hours, when microfilarial counts will be at least 90% of the peak
      counts. The circadian variation observed was independent of the subject's gender
      and microfilarial density. Mathematical analysis, using a simple harmonic-wave
      model, indicated a periodicity index of 127.6 and that maximum microfilarial
      densities occurred at 00.51 hours, confirming the nocturnal pattern of
      microfilaraemia in the study area.

PMID- 10945048
TI  - Urban/rural differences in prevalence and risk factors for intestinal helminth
      infection in southern Malawi.
AB  - Urbanization may increase the risk of human infection with intestinal helminths.
      A cross-sectional survey was conducted to investigate the prevalence, intensity
      and potential risk factors of acquiring such infection, among children aged 3-14
      years in similar urban and rural communities in southern Malawi. Stool samples
      were collected from 553 children (273 urban and 280 rural). The overall
      prevalence of helminth infection was significantly higher in the urban subjects
      than in the rural (16.5% v. 3.6%; P < 0.001), mostly because of differences in
      the prevalence of Ascaris lumbricoides infection. Living in an urban community
      was associated with a significantly higher risk of infection [odds ratio (OR) =
      5.3; 95% confidence interval (CI) = 2.6-12.1], even after controlling for
      potential confounding factors. In the urban community, risk factors included
      having pools of water/sewage around houses (OR = 3.0; CI = 1.4-6.5), not wearing
      shoes (OR = 7.1; CI = 2.7-19.2), not attending school (OR = 2.8; CI = 1.2-6.5),
      having mothers with 4-8 years of education (OR = 5.2; CI = 2.0-14.0), and having
      mothers below 35 years of age (OR = 4.09; CI = 1.39-16.28). In this part of
      Africa, efforts to reduce helminth infections may best be focused on reducing
      geohelminth burden in urban areas.

PMID- 10945049
TI  - Electrophysiological investigation of larval water and potential oviposition
      chemo-attractants for Anopheles gambiae s.s.
AB  - Potential Anopheles gambiae s.s. breeding sites were sampled in rural sites in
      the Tanga region of Tanzania. Sites containing the largest numbers of An. gambiae
      larvae were small, shaded pools and rice fields. Water samples were collected
      from the larval sites and these, together with ether extracts of the water
      samples, were active in electro-antennogram (EAG) studies with female mosquitoes
      from a laboratory colony of Anopheles (Cellia) gambiae KWA. EAG response
      thresholds varied for 10 randomly selected water samples, from 0.01%-100%
      dilution for the whole water samples and from 0.001%-1.0% dilution for the ether
      extracts. Potential chemical components of the water samples were also
      electrophysiologically active with female An. gambiae antennae; thresholds varied
      from 1 ng (3-methylindole and indole) to 10 micrograms (m-cresol and 4
      methylcyclohexanol).

PMID- 10945050
TI  - Plasmodium falciparum gametocytes in Gambian adults.

PMID- 10945051
TI  - Evaluation of malaria surveillance in Trinidad (1988-1998).

PMID- 10945053
TI  - Demonstration of botulinum toxins of types B and D in soil samples from Zambia.

PMID- 10945052
TI  - Antimalarial clinical trial protocols--can we avoid risk to patients?

PMID- 10945055
TI  - Publication ethics.

PMID- 10945054
TI  - Cases of apparent tick toxicosis in humans and dogs, caused by Ixodes redikorzevi
      s.l.

PMID- 10945056
TI  - Committee on Publication Ethics. The COPE Report 1999. Guidelines on good
      publication practice.

PMID- 10945057
TI  - Asthma prevalence in schoolchildren in a city in north-east Brazil.
AB  - Asthma is a disease of increasing prevalence all over the world. The objectives
      of this study were to describe the prevalence of asthma and aspects of its
      morbidity in schoolchildren in Recife, and to evaluate the relationship between
      maternal schooling and asthma prevalence during 1994-1995. This is part of an
      international, multicentre research project, the International Study of Asthma
      and Allergies in Childhood (ISAAC). In a cross-sectional design, a probabilistic
      sample of 1410 children of 6 and 7 years of age and 3086 teenagers of 13 and 14
      years were studied by questionnaire. The yearly prevalences of asthma symptoms in
      these two groups were 27.2% (CI 95%: 24.9-29.5%) and 18.1% (CI 95%: 16.4-19.8%),
      respectively; the cumulative prevalences of diagnosed asthma were 20.4% (CI 95%:
      17.8-23.0%) and 19.7% (CI 95%: 19.4-22.2%), respectively, and the prevalences of
      asthma according to severity were: mild--68.9% and 81.3%, moderate--24.2% and
      13.5%, severe--6.80% and 5.3%. During the previous year, the frequencies of
      crises with sleeping disorder were 23.2% and 13.0% and of disorder that limited
      speech 9.6% and 4.8%, respectively. There was a significant relationship between
      maternal education and cumulative prevalence of symptoms in both groups. It is
      concluded that asthma is a common disease which causes much morbidity in
      schoolchildren in Recife. The results suggest a relationship between low maternal
      education and a greater prevalence of asthma.

PMID- 10945058
TI  - Circumcision of the young infant in a developing country using the Plastibell.
AB  - Circumcision of the male infant by conventional methods is common practice in
      Tanzania. This study reports the use of the Plastibell to circumcise 386 young
      infants between 1992 and 1998 and shows differences in age at circumcision
      between African and Asian infants. The Plastibell has been found to be cheap and
      easy to use and was associated with minor, remediable complications in less than
      3% of infants.

PMID- 10945059
TI  - Unusual presentation of congenital syphilis.
AB  - Congenital syphilis (CS) usually presents in the neonatal period and may involve
      any organ system. The signs are diverse and a high index of suspicion must be
      maintained to make the diagnosis. Early congenital syphilis can present at any
      time before 2 years of age, but a review of the literature over the last 30 years
      indicates that it usually presents in the neonatal period and seldom later than 3
      4 months of life. We report an 8-month-old boy who presented an unusual
      combination of signs of congenital syphilis, which led to delay in establishing
      the diagnosis. This case emphasises the importance of maintaining a high index of
      suspicion for CS throughout early childhood.

PMID- 10945060
TI  - Childhood and adolescent growth of patients with sickle cell disease in Aracaju,
      Sergipe, north-east Brazil.
AB  - Sickle cell disease (SCD) is the most prevalent inherited monogenic pathology in
      South America. Although children with SCD have normal birthweight, weight deficit
      is often seen from early childhood. On the other hand, paradoxically, normal
      final height associated with delayed puberty has been reported from Brazil and
      Jamaica. This cross-sectional study describes the growth pattern by age and sex
      in 76 children and adolescents with SCD in Sergipe, north-east Brazil with a
      median age of 110 months. Median weights and heights for age were below the NCHS
      standards. The weight and height deficits were statistically significant for boys
      of all ages, except for 7-year-olds. Most girls have median weights and heights
      below the NCHS standards but this only becomes statistically significant at 15
      years of age. Family channels were calculated from the parents' heights. The
      observed height was lower than the expected percentile value for the family in
      seven (41%) children, equal to expected family height in six (35%) and above
      expected family height in four (24%) of 17 teenagers. Our findings suggest that
      Brazilian children with SCD do not attain normal height and weight. It is
      therefore likely that, although maximum height and weight velocity occur
      significantly later than normal due to delayed puberty, the magnitude of this
      spurt is less than normal.

PMID- 10945061
TI  - Evaluation of free radical status in CSF in childhood meningitis.
AB  - The study was undertaken to investigate the possible role of free radicals and
      antioxidants in childhood meningitis. Sixty children suffering from acute
      bacterial meningitis (ABM) or tuberculous meningitis (TBM) according to their
      clinical and laboratory findings were enrolled in the study. The production of
      superoxide anions (O2.-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) and
      the activities of xanthine oxidase (XO), superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) were monitored in the study groups and findings
      compared with those in 20 age-matched controls. Children with ABM and TBM who
      died registered significant increases in the production of O2.- and MDA and in
      the activities of SOD and CPK compared with survivors. The rate of production of
      oxidants and MDA and the activities of XO, SOD and CPK were of a much higher
      magnitude in deceased ABM and in ABM survivors than in fatal TBM and survivors,
      respectively. The abnormalities in most of the biochemical parameters
      investigated were more marked in the children with ABM than in TBM and controls
      (p < 0.001). Increased MDA production and creatine phosphokinase (CPK) activity
      of different magnitudes in the two study groups suggest varying degrees of tissue
      damage. The alterations observed in 20 children who died (14 from ABM, 6 from
      TBM) revealed elevated levels of oxidants, antioxidants and toxicity markers,
      particularly in ABM patients, which suggests the possibility that natural or
      synthetic antioxidants might prevent disease progression and tissue damage in
      childhood meningitis.

PMID- 10945062
TI  - Snake bites in children in The Gambia.
AB  - This is a retrospective study of the demographic features, treatment and outcome
      of 28 cases of snake bite admitted to the department of paediatrics of the Royal
      Victoria Hospital, Banjul, The Gambia over a 3-year period. The age range was 2
      14 years and the male:female ratio was 2.1:1. Most bites were on the legs and
      occurred near home. Most snake bites presented early at hospital and marked
      swelling of the affected limb was the most common clinical sign. Shock,
      restlessness and regional adenitis of the affected limb were common in children
      who died. The case fatality rate was 14.3%. Most children did not receive
      specific antivenom therapy.

PMID- 10945063
TI  - Extra-intestinal non-typhoidal Salmonella infections in children.
AB  - Extra-intestinal non-typhoidal Salmonella (NTS) infections are uncommon in
      developed countries but common in developing ones. The risk factors, clinical
      features and outcome of children admitted to the Department of Paediatrics,
      University of Malaya Medical Center, Kuala Lumpur from 1978 to 1998 with extra
      intestinal NTS infections were reviewed. All positive cultures of NTS, blood,
      cerebrospinal fluid, urine, synovial, pericardial and other body secretions
      (except stools), were included. Of the 98 cases reviewed, 56 were boys and 42
      girls. The mean age was 2.1 years (range: newborn to 14 years). Twenty-seven
      children were severely immunocompromised and 21 had underlying chronic medical
      disorders. Bacteraemia was the most commonly detected type of infection and
      meningitis the commonest focal infection. The overall mortality rate was 15%. An
      immunocompromised state or underlying chronic medical disorder was associated
      with increased mortality. The three serotypes most commonly isolated were S.
      enteritidis, S. paratyphi B and S. typhimurium. Most isolates were sensitive to
      antibiotics commonly used in salmonellosis.

PMID- 10945064
TI  - Childhood intussusception: a 9-year review.
AB  - Sixty-four consecutive cases of intussusception in 48 infants and 16 older
      children managed at Jos University Teaching Hospital between January 1990 and
      December 1998 are reviewed. The age range was between 3 months and 15 years (mean
      2.2 years) and the male to female ratio was 3.6:1. The quartet of abdominal pain,
      bloody mucoid stools, abdominal mass and palpable rectal mass was present in 70%
      compared with the classical triad (abdominal pain, bloody mucoid stools and
      abdominal mass) which occurred in only 32%. All the children had surgery. In 26
      (41%) of the children, no associated cause was found, in three polyps formed the
      lead point and in five children a buried appendicectomy stump formed the lead
      point. In 30 (47%) other children, mesenteric lymphadenopathy and inflamed
      Peyer's patches were noted. Ileo-colic intussusception occurred in 32 (50%)
      children. Manual reduction was successful in 67%. Bowel resection for gangrene,
      irreducibility and an iatrogenic colonic tear was done in 30% of patients. Two
      (3%) had spontaneous reductions. There were four deaths. The commonest
      complications were wound infection and adhesive intestinal obstruction.

PMID- 10945065
TI  - Pyogenic granuloma, a cause of congenital nasal mass: case report.
AB  - This is a case report of a 45-day-old Nigerian boy who presented with obstruction
      of the left nasal cavity since birth caused by a pyogenic granuloma which was
      successfully removed.

PMID- 10945066
TI  - Analysis of IgG isotype responses against Onchocerca volvulus antigens in
      children in an onchocerciasis-endemic area in northern Nigeria.
AB  - This study evaluated the usefulness of parasite-specific IgG and IgG isotype
      responses for diagnosing early or pre-patent onchocerciasis in children using
      sandwich ELISA. The children (n = 199) were aged between 5 and 12 years and
      living in a meso-endemic area of northern Nigeria. Only five had detectable skin
      microfilariae. The mean optical density (OD) values of children from the study
      area were significantly higher than those of normal controls' sera (n = 10, p <
      0.01), except for IgG2. There were 145 (73%) children positive for total IgG, 161
      (81%) for IgG1, 68 (34%) for IgG3 and 187 (94%) for IgG4 antibodies. The mean OD
      values of all antibodies tended to increase with age and peaked in the 9-10-year
      age group, except in the case of IgG3 which peaked at 11-12 years. IgG4 proved
      most sensitive compared with IgG, IgG1 and IgG3 in all age groups, and was
      significantly different (p < 0.05). Analysis by sex showed no significant
      difference between the boys and girls. We conclude that IgG4 serology is a useful
      diagnostic tool in the assay of early or pre-patent onchocerciasis in children.

PMID- 10945067
TI  - Outcome of minimal surgery for hydatid cysts of the liver in children with
      reference to post-operative biliary leakage.
AB  - Analysis of 30 children with hydatid cysts of the liver who were treated by
      partial pericystectomy and external tube drainage showed that five (21%) of 24
      cases in whom clear hydatid fluid was observed during surgery developed biliary
      leakage. The cysts in the remaining six contained bile-stained fluid, indicating
      the presence of cystobiliary communications, and five of these children continued
      to drain bile post-operatively, in spite of appropriate precautions taken during
      surgery. Histological examination of the pericyst wall confirmed the presence of
      openings of small bile ducts in the cyst which probably caused the biliary leak.
      It is possible that some larger openings were overlooked during surgery. It is
      concluded from this study that biliary leakage during the post-operative period
      should be expected in a significant number of patients subjected to surgery for
      hydatid cysts of the liver. However, the leak is likely to cease spontaneously,
      providing distal biliary duct obstruction is ruled out and external tube drainage
      is used to prevent accumulation of bile in the pericyst cavity.

PMID- 10945068
TI  - Pulmonary haemosiderosis in Saudi children: report of two cases and review of the
      literature.
AB  - Two children with idiopathic pulmonary haemosiderosis are reported. These are the
      first cases of this disease from Saudi Arabia and highlight the diagnostic
      problem caused by their presentation as cases of iron deficiency anaemia. The
      aetiopathogenesis, clinical presentation, diagnosis and management are discussed.
      The attention of paediatricians is drawn to this relatively rare cause of iron
      deficiency anaemia.

PMID- 10945069
TI  - Detection of pneumococcal capsular antigen in saliva of children with pneumonia.
AB  - The concentration of pneumococcal capsular antigen (PCA) in saliva was examined
      in 44 Thai children aged between 2 months and 2 years admitted with community
      acquired pneumonia and in 52 healthy controls. None of the children with
      pneumonia had a positive blood culture. PCA was detected by latex agglutination
      in the saliva of 12/44 (27%) children with pneumonia compared with 9/52 (17%) of
      the controls. More cases than controls had a PCA titre > or = 10 (9/44 (20%) vs
      1/52 (2%), p < 0.01). Three of the five cases with a saliva PCA titre > or = 1000
      were urine PCA antigen-positive. The salivary PCA titres were higher, but not
      significantly, in children with heavier pneumococcal carriage. Quantitative
      measurement of PCA in the saliva may be valuable in helping to make an
      aetiological diagnosis in children with pneumonia.

PMID- 10945070
TI  - Xerophthalmia and vitamin A deficiency in Nigeria.

PMID- 10945071
TI  - Aims, outcome measures, study sites and patient sample. EPSILON Study 1. European
      Psychiatric Services: Inputs Linked to Outcome Domains and Needs.
AB  - BACKGROUND: Cross-national research into the care of people with severe mental
      illnesses is hampered by a lack of standardised measures. The European
      Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) Study
      is a European Union funded project within the BIOMED-2 programme. The project
      aims to develop standardised instruments to facilitate future cross-national
      research. AIMS: To describe the aims, outcome measures, study sites and patient
      samples of the EPSILON Study. METHOD, RESULTS, CONCLUSIONS: See companion papers
      in this supplement.

PMID- 10945072
TI  - Translation and cross-cultural adaptation of outcome measurements for
      schizophrenia. EPSILON Study 2. European Psychiatric Services: Inputs Linked to
      Outcome Domains and Needs.
AB  - BACKGROUND: Research on the comparison of mental health services has identified
      the need for internationally standardised and reliable measurements. AIMS: To
      describe the strategies adopted in the European Psychiatric Services: Inputs
      Linked to Outcome Domains and Needs (EPSILON) Study for the translation and cross
      cultural adaptation of five European versions of the instruments. METHOD: A
      protocol was developed for translation of the outcome scales, describing each
      step in the translation procedure. Disputed items were discussed in focus groups,
      which faced seven tasks: a list of topics to be discussed; choosing where the
      group should meet; composition of participants; conducting the group; data
      collection; data completion afterwards; reporting results. RESULTS: Modifications
      made to instruments were: changes in the instrument structure, contents and
      concepts; adjustments to the instrument structure; and modifications to the
      instrument manual. CONCLUSION: Use of focus groups is an adequate method to apply
      if concepts, constructs and translation issues are to be addressed; otherwise,
      less time-consuming methods should be considered.

PMID- 10945073
TI  - Methodology of a multi-site reliability study. EPSILON Study 3. European
      Psychiatric Services: Inputs Linked to Outcome Domains and Needs.
AB  - BACKGROUND: The European Psychiatric Services: Inputs Linked to Outcome Domains
      and Needs (EPSILON) Study aims to produce standardised versions in five European
      languages of instruments measuring needs for care, family or caregiving burden,
      satisfaction with services, quality of life, and socio-demographic and service
      receipt. AIMS: To describe background, rationale and design of the reliability
      study, focusing on reliable instruments, reliability testing theory, a general
      reliability testing procedure and sample size requirements. METHOD: A strict
      protocol was developed, consisting of definitions of the specific reliability
      measures used, the statistical methods used to assess these reliability
      coefficients, the development of statistical programmes to make inter-centre
      reliability comparisons, criteria for good reliability, and a general format for
      the reliability analysis. CONCLUSION: The reliability analyses are based on
      classical test theory. Reliability measures used are Cronbach's alpha, Cohen's
      kappa and the intraclass correlation coefficient. Intersite comparisons were
      extended with a comparison of the standard error of measurement. Criteria for
      good reliability may need to be adapted for this type of study. The consequences
      of low reliability, and reliability differing between sites, must be considered
      before pooling data.

PMID- 10945074
TI  - Caregiving in schizophrenia: development, internal consistency and reliability of
      the Involvement Evaluation Questionnaire--European Version. EPSILON Study 4.
      European Psychiatric Services: Inputs Linked to Outcome Domains and Needs.
AB  - BACKGROUND: In international research on the consequences of psychiatric
      illnesses for relatives of patients, the need for an internationally standardised
      measure has been identified. AIMS: To test the internal consistency and the test
      retest reliability of the Involvement Evaluation Questionnaire (IEQ) in five
      European countries. METHOD: The IEQ was administered twice to a sample of
      relatives or friends of patients with an ICD-10 diagnosis of schizophrenia.
      Reliability was tested using Cronbach's alpha, intraclass correlation
      coefficients and standard error of measurement. Reliability estimates were tested
      between sites. RESULTS: Test sample sizes ranged from 30 to 90 across sites, and
      retest sample sizes ranged from 21 to 77. Cronbach's alpha values of IEQ sub
      scales and sumscore were substantial at most sites; but at two, alpha values were
      moderate. Intraclass correlation coefficients were substantial to high at all
      sites. The standard errors of measurement differed across sites, indicating
      differences in performance. CONCLUSION: The reliability of the IEQ in five
      languages varies across sites, but is sufficiently high in at least four out of
      five.

PMID- 10945075
TI  - Client Socio-Demographic and Service Receipt Inventory--European Version:
      development of an instrument for international research. EPSILON Study 5.
      European Psychiatric Services: Inputs Linked to Outcome Domains and Needs.
AB  - BACKGROUND: Cross-cultural comparison of mental health service utilisation and
      costs is complicated by the heterogeneity of service systems. For data to be
      locally meaningful yet internationally comparable, a carefully constructed
      approach to its collection is required. AIMS: To develop a research method and
      instrument for the collection of data on the service utilisation and related
      characteristics of people with mental disorders, as the basis for calculating the
      costs of care. METHOD: Various approaches to the collection of service use data
      and key stages of instrument development were identified in order to select the
      most appropriate methods. RESULTS: Based on previous work, and following
      translation and cross-cultural validation, an instrument was developed: the
      Client Socio-Demographic and Service Receipt Inventory--European Version (CSSRI
      EU). This was subsequently administered to 404 people with schizophrenia across
      five countries. CONCLUSION: The CSSRI-EU provides a standardised yet adaptable
      method for collating service receipt and associated data alongside assessment of
      patient outcomes.

PMID- 10945076
TI  - Reliability of the Camberwell Assessment of Need--European Version. EPSILON Study
      6. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs.
AB  - BACKGROUND: The five-country European Psychiatric Services: Inputs Linked to
      Outcome Domains and Needs (EPSILON) Study aimed to develop standardised and
      reliable outcome instruments for people with schizophrenia. This paper reports
      reliability findings for the Camberwell Assessment of Need--European Version (CAN
      EU). METHOD: The CAN-EU was administered in each country, at two points in time
      to assess test-retest reliability, and was rated by two interviewers at the first
      administration. Cronbach's alpha, test-retest reliability and interrater
      reliability were compared between the five sites. Reliability coefficients and
      standard errors of measurement for summary scores were estimated. RESULTS: Sites
      varied in levels and spread of needs. Alphas were 0.48, 0.58 and 0.64 for total,
      met and unmet needs respectively. Test-retest reliability estimates, pooled over
      sites, were 0.85 for the total needs, 0.69 for met needs and 0.78 for unmet
      needs. Pooled estimates for interrater reliability were higher, at 0.94, 0.85 and
      0.79 for total, met and unmet needs respectively. There were statistically
      significant differences in interrater reliability between sites. CONCLUSION: The
      results confirm the feasibility of using CAN-EU across sites in Europe and its
      psychometric adequacy.

PMID- 10945077
TI  - Development, internal consistency and reliability of the Verona Service
      Satisfaction Scale--European Version. EPSILON Study 7. European Psychiatric
      Services: Inputs Linked to Outcome Domains and Needs.
AB  - BACKGROUND: Satisfaction with mental health services is an important quality and
      outcome variable. The Verona Service Satisfaction Scale (VSSS) is a well
      established method for measuring service satisfaction. AIM: To report the
      development and reliability study of the European Version of the VSSS (VSSS-EU).
      METHOD: A sample of people with schizophrenia on the case-load of local mental
      health services in the five European participating countries was assessed. The
      VSSS-EU was administered at one site in each country at two points in time.
      Internal consistency and test-retest reliability were assessed and compared
      between the five sites. RESULTS: The alpha coefficient for the VSSS-EU total
      score in the pooled sample was 0.96 (95% CI 0.94-0.97) and ranged from 0.92 (95%
      CI 0.60-1.00) to 0.96 (95% CI 0.93-0.98) across the sites. Test-retest
      reliability for VSSS-EU total score, pooled over sites, was 0.82 (95% CI 0.78
      0.85) and ranged from 0.73 (95% CI 0.6-0.86) to 0.93 (95% CI 0.89-0.97) across
      the sites. CONCLUSION: VSSS-EU is a reliable instrument for measuring service
      satisfaction in people with schizophrenia, for use in comparative cross-national
      research projects and in routine clinical practice in mental health services
      across Europe.

PMID- 10945078
TI  - Quality of life in schizophrenia: development, reliability and internal
      consistency of the Lancashire Quality of Life Profile--European Version. EPSILON
      Study 8. European Psychiatric Services: Inputs Linked to Outcome Domains and
      Needs.
AB  - BACKGROUND: This paper, part of the European Psychiatric Services: Inputs Linked
      to Outcome Domains and Needs (EPSILON) Study, reports the development,
      reliability and internal consistency of the Lancashire Quality of Life Profile-
      European Version (LQoLP-EU) in a representative sample of people with
      schizophrenia from five European sites. METHOD: The LQoLP-EU was administered to
      a total sample of 404 patients to check its internal consistency, and a sub
      sample of 294 patients was interviewed a second time within 7-15 days to verify
      its test-retest reliability. RESULTS: Internal consistency of the total domains,
      perceived QoL scale (Life Satisfaction Scale, LSS) was good at 0.87. Of the nine
      subjective QoL domains Work and Leisure showed the lowest internal consistency
      (0.30 and 0.56 respectively), the values of the remaining sub-scales ranging
      between 0.62 and 0.88. The pooled ICC score for LSS was 0.82, and for the nine
      subjective QoL domain sub-scales it ranged from 0.61 (Safety) to 0.75 (Living
      Situation). There were significant differences between the sites in alpha and
      ICCs for sub-scales, but not for the LSS. CONCLUSION: The LQoLP-EU has good
      internal consistency and reliability in the five European centres.

PMID- 10945079
TI  - Psychiatry and Darwinism. Time to reconsider?

PMID- 10945080
TI  - Stigmatisation of people with mental illnesses.
AB  - BACKGROUND: Recognition of the additional social handicaps and distress that
      people with mental illnesses experience as a result of prejudice. AIMS: To
      determine opinions of the British adult population concerning those with mental
      illnesses as baseline data for a campaign to combat stigmatization. METHOD:
      Survey of adults (n = 1737 interviewed; 65% response) regarding seven types of
      common mental disorders. Responses evaluated concerned eight specified
      perceptions. RESULTS: Respondents commonly perceived people with schizophrenia,
      alcoholism and drug addiction as unpredictable and dangerous. The two latter
      conditions were also viewed as self-inflicted. People with any of the seven
      disorders were perceived as hard to talk with. Opinions about effects of
      treatment and prognosis suggested reasonable knowledge. About half the
      respondents reported knowing someone with a mental illness. CONCLUSIONS: Negative
      opinions indiscriminately overemphasize social handicaps that can accompany
      mental disorders. They contribute to social isolation, distress and difficulties
      in employment faced by sufferers. A campaign against stigma should take account
      of the differences in opinions about the seven disorders studied.

PMID- 10945081
TI  - Cognitive therapy and recovery from acute psychosis: a controlled trial. 3. Five
      year follow-up.
AB  - BACKGROUND: This paper describes the 5-year outcome of a cohort of patients who
      had received a cognitive therapy intervention during an acute episode of non
      affective psychosis. METHOD: Thirty-four out of the original 40 patients who had
      taken part in a randomised controlled trial of a cognitive intervention were
      assessed, using standardised instruments completed at entry into the study. In
      the original trial, half the patients received a cognitive therapy programme (CT
      group) and the other half received recreational activities and support (ATY
      group). RESULTS: At follow-up no significant differences in relapse rate,
      positive symptoms or insight between the groups were found, although the CT group
      did show significantly greater perceived 'Control over illness' than the ATY
      group. For individuals who had experienced a maximum of one relapse in the follow
      up period, self-reported residual delusional beliefs and observer-rated
      hallucinations and delusions were significantly less in the CT than in the ATY
      group. CONCLUSION: Cognitive therapy applied in the acute phase of a psychotic
      disorder can produce enduring and significant clinical benefits if experience of
      relapse can be minimised.

PMID- 10945082
TI  - Factor structure and familiality of first-rank symptoms in sibling pairs with
      schizophrenia and schizoaffective disorder.
AB  - BACKGROUND: Since their introduction as diagnostic criteria by Schneider in 1937,
      nuclear symptoms have played a key role in concepts of schizophrenia, but their
      relationship to each other and to genetic predisposition has been unclear. AIMS:
      To ascertain the factor structure and familiality of nuclear symptoms. METHODS:
      Nuclear (Schneiderian) symptoms were extracted from case notes and interviews in
      a study of 103 sibling pairs with DSM-III-R schizophrenia or schizoaffective
      disorder. RESULTS: Principal components analysis demonstrated two major factors:
      one, accounting for about 50% of the variance, groups thought withdrawal,
      insertion and broadcasting, with delusions of control; and the second, accounting
      for < 20% of the variance, groups together third-person voices, thought echo and
      running commentary. Factor I was significantly correlated within sibling pairs.
      CONCLUSIONS: The correlation within sibling pairs suggests that, contrary to the
      conclusion of some previous studies, some nuclear symptoms do show a degree of
      familiality and therefore perhaps heritability.

PMID- 10945083
TI  - Causes of schizophrenia reported by patients' family members in China.
AB  - BACKGROUND: Better methods of assessing patients' and family members' causal
      models of illness are needed to improve adherence with biomedical interventions
      and to design services that meet the needs of consumers. AIMS: To develop a
      quantitative measure suitable for assessing the relationship of causal beliefs to
      expressed emotion, stigma, care-seeking and adherence. METHOD: The Causal Models
      Questionnaire for Schizophrenia, which includes 45 causes identified during in
      depth interviews with family members, was administered to 245 family members of
      135 patients with DSM-III-R schizophrenia in Suzhou and Siping, China at the time
      of admission to hospital. RESULTS: Respondents, who identified a mean of 2.5
      causes (range 1-10, mode 2), attributed 84% of the cause of schizophrenia to
      social, interpersonal and psychological problems. Hence, their beliefs do not
      concur with Chinese professionals' ideas about the biomedical causes of
      schizophrenia. Multivariate analyses identified the socio-economic factors that
      influence family members' causal beliefs. CONCLUSIONS: Despite the complexity of
      causal models, measures can be developed that will help improve clinicians'
      communication with patients and understanding of help-seeking behaviours.

PMID- 10945084
TI  - Cognitive and behavioural functioning in men with schizophrenia both before and
      shortly after first admission to hospital. Cross-sectional analysis.
AB  - BACKGROUND: The extent of premorbid changes associated with the onset of
      schizophrenia are debated. AIMS: The study examined cognitive and behavioural
      functioning prior to, and after, first hospitalisation for schizophrenia. METHOD:
      Data from the Israeli Draft Board Register of intelligence, social functioning
      and behaviour testing for all Israeli males aged 16-17 was linked with data from
      the National Psychiatric Hospitalisation Case Register. This identified 692 men
      who had been admitted to hospital for schizophrenia. Cases and non-cases matched
      on age and school were compared, as were cases aggregated by the time that had
      elapsed between testing and first admission to hospital. RESULTS: Cases performed
      worse than non-cases on all measures. On Social Functioning and on Raven's
      Progressive Matrices-R, differences between cases and non-cases were
      progressively greater for cases admitted closer to the time of testing. These
      differences were greatest for persons tested after first psychiatric
      hospitalisation. CONCLUSIONS: The results confirm premorbid deficits associated
      with schizophrenia and support the hypothesis that decline is progressive.

PMID- 10945085
TI  - Psychiatric patients at greatest risk and in greatest need. Impact of the
      Supervision Register Policy.
AB  - BACKGROUND: Mental health provider trusts in England were required in 1994 to
      establish local Supervision Registers of patients at risk. AIMS: To identify the
      factors associated with registration, and obtain clinicians' views on its
      effectiveness. METHOD: At a random sample of 14 trusts data were collected from
      case notes, key workers and responsible medical officers. RESULTS: A sample of
      133 registered patients were more disabled and had more extensive histories of
      violence and self-harm than 126 comparison patients on the upper tier of the Care
      Programme Approach (CPA). Those registered were a heterogeneous group. For some
      there was little evidence of risk. In most cases clinicians did not believe
      registration had improved care. CONCLUSIONS: The Supervision Register policy has
      not resulted in the identification of a well-defined group. Its effectiveness is
      limited by the lack of operationalized measures of risk.

PMID- 10945086
TI  - Schizophrenia is not disappearing in south-west Scotland.
AB  - BACKGROUND: Recent work has reported a decline in the incidence of schizophrenia,
      but it is unclear if these findings reflect a true decrease in its incidence or
      are an artefact arising from methodological difficulties. AIMS: To take account
      of these methodological difficulties and report service-based incidence rates for
      schizophrenia in Dumfries and Galloway in south-west Scotland for 1979-98.
      METHOD: Using both clinical diagnoses and diagnoses generated from the
      Operational Checklist for Psychotic Disorders (OPCRIT) computer algorithm for ICD
      10 and DSM-IV schizophrenia, we measured change in the incidence rates over time.
      We used indirect standardisation techniques and Poisson models to measure the
      rate ratio linear trend. RESULTS: There was a monotonic and statistically
      significant decline in clinically diagnosed schizophrenia. The summary rate ratio
      linear trend was 0.77. However, using OPCRIT-generated ICD-10 and DSM-IV
      diagnoses, there was no significant difference over time. CONCLUSIONS: OPCRIT
      generated consistent diagnoses revealed no significant fall in the incidence of
      schizophrenia. Changes in diagnostic practice have caused the declining rates of
      clinically diagnosed schizophrenia in Dumfries and Galloway.

PMID- 10945087
TI  - Self-report quality of life measure for people with schizophrenia: the SQLS.
AB  - BACKGROUND: Quality of life is the subject of growing interest and investigation.
      AIMS: To develop and validate a short, self-report quality of life questionnaire
      (the Schizophrenia Quality of Life Scale, SQLS). METHOD: People with
      schizophrenia in Liverpool were recruited via the NHS. Items, generated from in
      depth interviews, were developed into an 80-item self-report questionnaire. Data
      were factor analysed, and a shorter form measure was tested for reliability and
      validity. This measure was administered together with other self-report measures-
      SF-36, GHQ-12 and HADS--to assess validity. RESULTS: Data were analysed to
      produce a final 30-item questionnaire, comprising three scales ('psychosocial',
      'motivation and energy', and 'symptoms and side-effects') addressing different
      SQLS dimensions. Internal consistency reliability of the scale was found to be
      satisfactory. There was a high level of association with relevant SF-36, GHQ-12
      and HADS scores. CONCLUSIONS: The SQLS was completed within 5-10 minutes. It
      possesses internal reliability and construct validity, and promises to be a
      useful tool for the evaluation of new treatment regimes for people with
      schizophrenia.

PMID- 10945088
TI  - Critical approach to antidepressant trials. Blindness protection is necessary,
      feasible and measurable.
AB  - BACKGROUND: Double-blind placebo-controlled trials are the academic standard for
      clinical psychopharmacology research. AIMS: To identify the potential defects of
      current double-blind procedures in trials involving antidepressants and to
      investigate whether safeguards for blindness protection are used. METHOD: We
      reviewed the literature and devised a short seven-item checklist for evaluating
      the quality of blindness protection. We performed a computerised search for 1998
      to identify the placebo-controlled studies that evaluated the efficacy of an
      antidepressant. The checklist was used to assess all traceable antidepressant
      trials published in 1998. RESULTS: Relevant criticisms question the blindness
      procedures. The available methods which may bolster blindness are very seldom
      used. CONCLUSIONS: Improvement in the blindness procedures used for
      antidepressant trials is necessary, feasible and measurable.

PMID- 10945089
TI  - Child and adolescent mental health service use. HoNOSCA as an outcome measure.
AB  - BACKGROUND: HoNOSCA (Health of the Nation Outcome Scales for Children and
      Adolescents) is a recently developed measure of outcome for use in child and
      adolescent mental health services (CAMHS). AIMS: To examine HoNOSCA's sensitivity
      to change, convergent validity and clinical usefulness. METHOD: Prospective study
      of new CAMHS attenders. Questionnaires completed by clinicians, parents and
      referrers at initial assessment and after 6 months. RESULTS: Follow-up HoNOSCAs
      on 203 children indicated statistically significant change. There were
      significant associations between change in HoNOSCA scores, changes in other
      clinician- and parent-rated scales (r = 0.51 to 0.32) and in global outcome
      ratings by referrers, parents and clinicians. Intraclass correlation coefficients
      for the summated HoNOSCA scores were high. HoNOSCA change was positively
      correlated with initial HoNOSCA score (r = 0.46, P < 0.001) and it was linked to
      psychiatric diagnosis. CONCLUSIONS: HoNOSCA is a sensitive, valid measure of
      change among CAMHS attenders.

PMID- 10945090
TI  - Predictors of psychopathology in young adults referred to mental health services
      in childhood or adolescence.
AB  - BACKGROUND: For children referred to mental health services future functioning
      may be hampered. AIMS: To examine stability and prediction of behavioural and
      emotional problems from childhood into adulthood. METHOD: A referred sample (n =
      789) aged 4-18 years was followed up after a mean of 10.5 years. Scores derived
      from the Child Behavior Checklist, Youth Self-Report and Teacher Report Form were
      related to equivalent scores for young adults from the Young Adult Self-Report
      and Young Adult Behavior Checklist. RESULTS: Correlations between first contact
      (T1) and follow-up (T2) scores were 0.12-0.53. Young adult psychopathology was
      predicted by corresponding T1 problem scores. Social problems and
      anxious/depressed scores were predictors of general problem behaviour.
      CONCLUSIONS: Problem behaviour of children and adolescents referred to outpatient
      mental health services is highly predictive of similar problem behaviour at young
      adulthood. Stability is higher for externalizing than for internalizing behaviour
      and for intra-informant than for inter-informant information. Stabilities are
      similar across gender. To obtain a comprehensive picture of the young adult's
      functioning, information from related adults may prove valuable.

PMID- 10945091
TI  - Long-term predictors of cognitive outcome in a cohort of older people with
      hypertension.
AB  - BACKGROUND: Deteriorating cognitive function in late life substantially increases
      the risk for dementia, for other non-cognitive morbidity, for dependency, and
      early death. AIMS: To identify early predictors of late-life cognitive outcome.
      METHOD: Cognitive function, premorbid IQ, and cardiovascular risk exposure were
      recorded on 1083 subjects on entry to a hypertension treatment trial in 1983
      1984. We followed up this cohort 9-12 years later to assess cognitive function
      with the Mini-Mental State Examination (MMSE), to update exposure status, and to
      obtain genomic material. Multivariate analysis was used to identify independent
      baseline predictors of cognitive outcome 9-12 years later. RESULTS: We followed
      up 387 subjects (58.6% of survivors). After adjusting for baseline cognition,
      poorer cognitive outcome was found to be independently associated with a family
      history of dementia, increasing age, less decline in systolic blood-pressure,
      lower premorbid IQ (rather than limited education), and abstinence from alcohol.
      CONCLUSIONS: Reduction in systolic blood pressure (among hypertensives) and
      moderate alcohol intake could protect against cognitive deterioration in late
      life.

PMID- 10945092
TI  - Reliability of lifetime history of bulimia nervosa. Comparison with major
      depression.
AB  - BACKGROUND: Previous studies have found that the reliability of the lifetime
      prevalence of bulimia nervosa is low to moderate. However, the reasons for poor
      reliability remain unknown. AIMS: We investigated the ability of a range of
      variables to predict reliability, sensitivity, and specificity of reporting of
      both bulimia nervosa and major depression. METHOD: Two interviews, approximately
      5 years apart, were completed with 2163 women from the Virginia Twin Registry.
      RESULTS: After accounting for different base rates, bulimia nervosa was shown to
      be as reliably reported as major depression. Consistent with previous studies of
      major depression, improved reliability of bulimia nervosa reporting is associated
      with more severe bulimic symptomatology. CONCLUSIONS: Frequent binge eating and
      the presence of salient behavioural markers such as vomiting and laxative misuse
      are associated with more reliable reporting of bulimia nervosa. In the absence of
      the use of fuller forms of assessment, brief interviews should utilise more than
      one prompt question, thus increasing the probability that memory of past
      disorders will be more successfully activated and accessed.

PMID- 10945093
TI  - Total serum cholesterol in relation to psychological correlates in parasuicide.
AB  - BACKGROUND: Low cholesterol may act as a peripheral marker for parasuicide. AIMS:
      To examine the relationship between total serum cholesterol and psychological
      parameters in parasuicide. METHOD: Total serum cholesterol and self-rated scores
      for impulsivity, depression and suicidal intent were measured in 100 consecutive
      patients following parasuicide, pair-matched with normal and psychiatric control
      groups. RESULTS: Backward, stepwise multiple regression analysis revealed a
      significantly lower mean cholesterol in the parasuicide population (P < 0.01).
      Across all groups there was an independent significant (P < 0.01) negative
      correlation between cholesterol and self-reported scores of impulsivity. No
      correlation existed between cholesterol and scores for depression or suicidal
      intent. CONCLUSIONS: The data confirm previous reports of low cholesterol in
      parasuicide. This is the first reported investigation of the construct of
      impulsivity in relation to cholesterol. We hypothesise that the reported
      increased mortality in populations with low cholesterol may derive from increased
      suicide and accident rates consequent on increased tendencies to impulsivity in
      these populations.

PMID- 10945094
TI  - Decreasing suicide in Hungary.

PMID- 10945095
TI  - Drug dependence and child abuse.

PMID- 10945096
TI  - Relevance of Schneider's first-rank symptoms.

PMID- 10945097
TI  - Social anxiety in patients with facial disfigurement.

PMID- 10945098
TI  - Outcome of hospital-treated depression.

PMID- 10945099
TI  - Anorexia nervosa: treatment with olanzapine.

PMID- 10945100
TI  - Nicotine reduction: effectiveness of bupropion.

PMID- 10945101
TI  - Paradoxical pattern of haematological risk with clozapine.

PMID- 10945102
TI  - Hospital Anxiety and Depression Scale for use with adolescents.

PMID- 10945103
TI  - The fate of added nitrate used in the manufacture of Emmental cheese.
AB  - The aim of this study was to observe the dynamics of nitrates and nitrites during
      the six stages of manufacture of Emmental cheeses. Samples were taken of
      untreated milk, of pasteurized milk, of milk with nitrates added, of pressed
      cheese curd, of whey, of maturing cheese and of the final product. The samples
      were drawn from a commercial operation in a cheese factory in the eastern part of
      Slovakia. The mean NaNO2 content in untreated and in pasteurised milk was 0.2 and
      0.1 mg kg-1, respectively and the mean NaNO3 content was 0.9 and 0.9 mg kg-1
      respectively. Nitrates were added to the milk to prevent 'blowing' of hard cheese
      by micro organisms. In milk with nitrate added the mean content was 81.2 mg kg-1
      NaNO3; the maximum value being 90.0 mg kg1 NaNO3. After pressing, the mean value
      of nitrate was found to be 20.6 mg kg-1 NaNO3. A considerable quantity of
      nitrates passed into the whey, where the mean nitrate content was 67.0 mg kg-1
      NaNO3. The final product had a markedly decreased content of nitrates (3.3 mg kg
      1 NaNO3) and nitrites (0.2 mg kg-1 NaNO2) when compared with the values in cheese
      during maturation (11.3 mg kg-1 NaNO3; 0.4 mg kg-1 NaNO2).

PMID- 10945105
TI  - Effects of temperature on the elimination of benzocaine and acetylated benzocaine
      residues from the edible fillet of rainbow trout (Oncorhynchus mykiss).
AB  - The effect of temperature (7 degrees C and 16 degrees C) on the extent of
      accumulation and the elimination of benzocaine (BNZ) and its metabolite,
      acetylated benzocaine (AcBNZ), in the fillet tissue of rainbow trout was
      investigated. Residues were measured after bath exposure to an anesthetizing
      concentration of benzocaine (30 mg/l for 5 min) followed by a maintenance
      concentration (15 mg/l for 30 min). Immediately after exposure, the BNZ
      concentration in fillet tissue was approximately 27 micrograms/g at both
      temperatures; AcBNZ was 0.3 microgram/g at 7 degrees C and 0.6 microgram/g at 16
      degrees C. The rates for elimination (alpha and beta) of BNZ and AcBNZ were not
      significantly different between the two temperatures. Terminal half-lives of
      elimination for BNZ were 1.62 h at 7 degrees C and 1.63 h at 16 degrees C; half
      lives for AcBNZ were 2.36 h at 7 degrees C and 2.77 h at 16 degrees C.

PMID- 10945104
TI  - Generation of aniline from a subsidiary colour of food yellow no. 5 (sunset
      yellow FCF).
AB  - The formation of aniline from sodium salt of 6-hydroxy-5-(phenylazo)-2
      naphthalenesulphonic acid (SS-AN, C.I. 15970, Orange RN), a subsidiary colour in
      the Japanese colour additive Food Yellow No. 5 (Y-5, C.I. 15985, Sunset Yellow
      FCF), was investigated in the artificial gastric fluid (AGF) and in the
      artificial intestinal fluid (AIF) as prescribed in the degradation test in the
      Japanese Pharmacopoeia (1996). Aniline concentrations of 0.3-6.8 micrograms/ml
      were found in 0.1% SS-AN solutions with 0.1-5.0% ascorbic acid or erythorbic acid
      after 24 h at 37 degrees C. This simulates a mixture of dye and ascorbic acid
      that might be ingested. The amount of aniline generated depended upon the
      temperature in these systems. In systems to which sucrose had been added, an
      increase in the amount of aniline generated was observed. However, no aniline
      generation was observed in the 0.1% SS-AN solutions in the AGF or AIF at 37
      degrees C for 24 h. Furthermore, the generation of aniline was not seen in AGF
      and AIF at higher temperatures in the range of 37-80 degrees C. It was not
      generated by the degradation of SS-AN in the presence of digestive enzymes.

PMID- 10945106
TI  - The fate and persistence of zineb, maneb, and ethylenethiourea on fresh and
      processed tomatoes.
AB  - Tomatoes grown under greenhouse conditions were sprayed with radiolabelled maneb
      and zineb to determine the extent of degradation of these fungicides to
      ethylenethiourea (ETU) and to study the persistence of ETU on the fruits. The
      total (14C) residues decreased from 0.082 mg/kg and 0.11 mg/kg at day 0 to 0.023
      mg/kg and 0.05 mg/kg at day 20, on zineb- and maneb-treated fruits, respectively.
      This reduction was mainly due to the rapid growth of the fruits. ETU residues on
      tomato fruits were found to decline with time. A sharp reduction in ETU content
      was observed during the first 24 h after treatment, followed by a slow decline in
      the following 5 days. ETU content was reduced by about 80% by day 20 after the
      fungicide application, and the concentration of EU, the major degradation product
      of ETU, doubled during the same period. Studies with tomatoes fortified with
      (14C) ETU (0.006 mg/kg) prior to processing into tomato paste showed that 70% of
      the radioactivity was lost during washing of the tomatoes in water. Further
      losses of ETU occurred during boiling of the juice (6%) and during storage of the
      tomato paste for a period of 3 weeks (3%).

PMID- 10945107
TI  - Patulin in apple-based foods: occurrence and safety evaluation.
AB  - Patulin is a mycotoxin produced by certain species of Penicillium and
      Aspergillus, often detectable in mouldy fruits and their derivatives. On the
      basis of a PMTDI of 0.4 microgram/kg bw, limit values of 50 micrograms/kg or 50
      micrograms/l of patulin have been set in fruit derivatives. To estimate the
      quantity of patulin that can be taken in with the diet, we analysed by HPLC
      samples of apples and apple derivatives which are most likely to be contaminated
      with patulin. In apple juices and in homogenized baby-foods, the mycotoxin
      concentration was always below the established limits, while in some samples of
      juice with pulp the mycotoxin content exceeded the safe levels. In rotten apples,
      not only was the amount of patulin extraordinarily high in the rotten area, but
      the mycotoxin had also spread to the part unaffected by mould. The data presented
      in this study indicate that the intake of patulin with apple derivatives is
      usually below the tolerable level of 0.4 microgram/kg bw/day, but since the
      patulin content in apples can vary considerably, the quality of fruits used in
      the production of apple derivatives should be strictly controlled in order not to
      exceed the safe limits.

PMID- 10945108
TI  - Survey for aflatoxins, ochratoxin A, zearalenone and fumonisins in maize imported
      into the United Kingdom.
AB  - This survey examined 140 samples of raw maize as received at ports or at major
      maize mills in the UK and 12 after initial cleaning. Samples were examined for
      aflatoxins B1, B2, G1 and G2, ochratoxin A, zearalenone and fumonisins B1, B2 and
      B3 using fully validated analytical HPLC methods with detection limits of 0.1
      microgram/kg for each aflatoxin and ochratoxin A, 4 micrograms/kg for zearalenone
      and 10 micrograms/kg for each fumonisin. 95.0% and 92.1% of samples met the new
      EC statutory maximum permissible level for total aflatoxins and aflatoxin B1
      respectively. The maximum concentration of ochratoxin A found was 1.5
      micrograms/kg. Zearalenone and fumonisins were detected in almost every sample
      with 41.7% of maize containing more than 100 micrograms/kg of zearalenone and 48%
      of samples containing more than 1000 micrograms/kg total fumonisins. Initial
      cleaning of raw maize reduced aflatoxin concentrations by about 40% and total
      fumonisins by 32%.

PMID- 10945109
TI  - Alkyltins in farmed fish and shellfish.
AB  - A study to update dibutyltin (DBT) and tributyltin (TBT) residues in farmed fish
      and shellfish (Mytilus edulis) was carried out 4 years after the adopting of the
      restricting regulation of the antifouling uses of organotins in Italy. DBT and
      TBT were simultaneously extracted from farmed fish and shellfish (M. edulis) and
      from free living specimens, used as control, purchased from retail stores or
      fishermen in the province of Naples (Italy), and detected using a capillary gas
      chromatograph equipped with a flame photometric detector (GC-FPD). Dosable
      amounts of DBT were found in the 10% of the farmed fish analyzed, ranging from 1
      to 26 micrograms kg-1 wet wt (mean 10 micrograms kg-1) and in the 23% of the free
      living fish at an average level of 2 micrograms kg-1 wet wt (range 1-4 micrograms
      kg-1 wet wt). TBT was detected in 85% of the farmed fish, in concentrations
      varying from 2 to 260 micrograms kg-1 wet wt (mean 28 micrograms kg-1 wet wt) and
      in 46% of the free living specimens (mean 39 micrograms kg-1 wet wt; range 1-93
      micrograms kg-1). All the mussel samples analyzed were polluted by both DBT and
      TBT. In the farmed mussels the average amounts of DBT and TBT were, respectively,
      4 and 2 micrograms kg-1 wet wt; in the free living they were 4 and 5 micrograms
      kg-1 wet wt, respectively. The results indicate that the DBT and TBT
      contamination is as highly diffuse in farmed as in free living fish and mussels
      on sale in retail markets in Naples province even if the levels of the
      contamination are meanly quite low.

PMID- 10945110
TI  - Fiber intake and childhood appendicitis.
AB  - In order to investigate the possible role of fiber in the etiology of acute
      appendicitis, 203 consecutive appendectomized children with histologically proved
      appendicitis and 1922 controls were studied by the diet history method.
      Statistics were performed by multivariate analysis of variance, discriminant
      analysis and chi 2. Appendectomized children had statistically significant lower
      mean daily intake of fiber (17.4 g versus 20.4 g, P < 0.001) including all fiber
      fractions: cellulose, uronic acid, pentose, exose and lignin. No statistical
      difference was found for energy, protein, carbohydrate and fat intake.
      Discriminant analysis proved that only cellulose and exose are independently
      correlated to appendicitis and lower fiber intake is thought to be the cause in
      70% of the cases. Recurrent abdominal pain, chronic constipation and positive
      family history of appendectomy were more frequent in appendectomized children (P
      < 0.001). This study gives evidence that low fiber intake could play an important
      role in the pathogenesis of appendicitis.

PMID- 10945112
TI  - Effect of cooking and supplementation with different kinds of meats on the
      nutritional value of mash (Vigna mungo).
AB  - The study was conducted to determine the nutritional value of mash (Vigna mungo)
      in raw and cooked forms and as effected by supplementation with different kind of
      meat, i.e. poultry, mutton and beef at 10, 15 and 20% levels. Nutritional
      assessment of all mash-containing diets (without or with supplementation) was
      made by chemical analysis as well as through rat assay. Mash contained 23.83%
      protein. Cooking resulted in minor changes in nutrients. Mash had 1.79% lysine
      which was reduced by 35% on cooking. All other amino acids also showed losses
      during cooking. Protein efficiency ratio (PER) of diet containing raw mash was
      1.9% and cooking improved it to 2.8%. True digestibility (TD) also showed a
      significant improvement. Supplementation of mash with different kinds of meat did
      not improve the PER significantly over unsupplemented diet containing cooked mash
      only. TD, however, was improved from 74.89% in cooked to 75.58-87.06% in
      supplemented diets. Similarly net protein utilization (NPU), as a result of meat
      supplementation, improved from 43.54% in cooked to 42.88%-51.96%. Higher PER, TD
      and NPU values were observed in diets containing mash supplemented with 20% level
      of different meats.

PMID- 10945111
TI  - Growth and lipid metabolism responses in rats fed different dietary fat sources.
AB  - An experiment with male albino rats was conducted to examine the effect of
      dietary fat sources on growth performance and apparent digestibility of total fat
      and fatty acids. The effect on plasma and organ cholesterol concentrations as
      well as lipoproteins cholesterol and fatty acid profile of hepatic phospholipids
      was also examined. Forty 3 week old rats were fed purified diets containing
      0.041% cholesterol and 7% fat (wt/wt) from soy oil (SO), or cow ghee (GH), or 25%
      fish oil (FO) plus soy oil (SF) or 25% fish oil plus 75% ghee (GF), or 50% soy
      oil plus 50% ghee (SG) for a period of 35 days. Final body weight, weight gain,
      organ weights and feed efficiency ratio showed no significant differences (P <
      0.05) among the dietary treatments. The apparent digestibility of total dietary
      fat and saturated fatty acids in the animals fed diet containing cow ghee only or
      in combination with fish oil or soy oil was significantly lower than the other
      dietary groups. Consumption of ghee with combination of fish oil or soy oil lead
      to significant improvement in the fat apparent digestibility of dietary fat.
      Total cholesterol and triglyceride concentrations of plasma and organs as well as
      lipoprotein cholesterol levels were higher in animals fed diets containing ghee.
      For rats fed diet containing cow ghee in combination with fish oil or soy oil,
      the cholesterol content of total plasma, lipoprotein fractions (VLDL, LDL and
      HDL) and organs was decreased significantly. Furthermore, dietary fats altered
      the fatty acids composition of hepatic phospholipid fatty acids composition.
      Feeding dietary fish oil reduced arachidonic acid (20:4) and increased linoleic
      acid (18:2) and eicosapentaenoic acid (20:5) contents. The reduction in the
      arachidonic acid was being more pronounced in animals fed dietary ghee with
      combination of fish oil.

PMID- 10945113
TI  - Mini-papad containing cheese powder--a novelty snack food.
AB  - The present work reports on attempts to develop mini-papads containing cheese
      powder to create a novel taste, with potential for urban and export markets.
      Cheese powder was added to black gram flour at 0-50% levels and papads were
      prepared in the conventional manner by rolling the dough and drying. These papads
      were deep-fat fried at 180 degrees C. Upto 20% addition of cheese powder gave no
      perceptible change in taste or flavour of the mini-papads. At 30% addition brown
      colouration was observed which decreased the sensory appeal. At 40 and 50%
      levels, although the mouthfeel and flavour of cheese was desirable, browning
      increased markedly, which drastically lowered the overall acceptability. Ascorbic
      acid addition at 0.5-1.0% markedly decreased the browning. The papads had a
      higher fat content on frying as compared to the control but were excellent
      organoleptically, suggesting them to be a tasty and crunchy snack food.

PMID- 10945114
TI  - Antioxidant potential of green and black tea determined using the ferric reducing
      power (FRAP) assay.
AB  - Tea is one of the most commonly consumed beverages in the world and is rich in
      polyphenolic compounds collectively known as the tea flavonoids. Tea flavonoids
      possess antioxidant properties in vitro and have been proposed as key protective
      dietary components, reducing risk of coronary heart disease and some cancers. The
      present study aimed to evaluate the possible effects of different preparation
      methods on the antioxidant properties of green and black tea. Antioxidant
      potentials of tea infusates were assessed using an assay based upon the reduction
      of ferric chloride linked to a chromophore. Green tea, black leaf tea and black
      tea in tea bags were infused with water at 90 degrees C for time periods ranging
      from 0.25 to 15 min. Green tea infusates possessed approximately 2.5-fold greater
      antioxidant capacity than both types of black tea infusates. Both green and black
      teas released significant levels of antioxidants into the hot water within 2 min
      of infusion. Preparation of teas across a range of temperatures between 20 and 90
      degrees C revealed that although antioxidants were liberated from the leaves into
      the water in cooler infusions, increasing the temperature could increase
      antioxidant potential by 4 to 9.5-fold. Black tea prepared using tea bags had
      significantly lower antioxidant capacity than black leaf tea at temperatures
      between 20 and 70 degrees C, suggesting that tea bag materials may prevent some
      extraction of flavonoids into the tea solution. The addition of milk appeared to
      diminish the antioxidant potential of black tea preparations. This effect was
      greatest where whole cow's milk was used and appeared to be primarily related to
      the fat content of the added milk. These experiments have considered the effects
      of commonly used domestic methods of preparation on the in vitro antioxidant
      potential of tea. It is concluded that maximum antioxidant capacity and hence
      maximal health benefit may be derived from green tea or from black leaf tea
      prepared by infusion with water at 90 degrees C for up to 2 min and taken with
      the addition of either fat-free milk, or without milk addition. Further studies
      are required to assess the antioxidant actions of tea flavonoids in vivo.

PMID- 10945115
TI  - Proximate composition, phytic acid, polyphenols and digestibility (in vitro) of
      four brown cowpea varieties.
AB  - Four cultivars of brown cowpea (Vigna unguiculata. L. Walp) were analysed for
      their proximate composition, phytic acid, polyphenols and protein and starch
      digestibility (in vitro). Crude protein values ranged from 20.07 to 24.60%. Ether
      extract and crude fiber contents varied from 1.77 to 1.96% and 4.27 to 4.95%,
      respectively. All the four cowpea varieties differed significantly for their
      starch content which ranged from 46.84 to 53.63%. Antinutrients, phytic acid and
      polyphenols, showed significant variations among the varieties. In vitro
      digestibility of protein and starch of grains had a narrow variation. The variety
      CS-46 containing minimum amount of antinutritional factors had the highest
      protein digestibility.

PMID- 10945116
TI  - Energy and micronutrient composition of dietary and medicinal wild plants
      consumed during drought. Study of rural Fulani, northeastern Nigeria.
AB  - Two rural settled Fulani villages, northeastern Nigeria, were surveyed for
      dietary practices and use of edible wild plants (n = 100 households). Commonly
      consumed species of edible wild barks, fruits, leaves, nuts, seeds, and tubers
      were analyzed for protein, fat, and carbohydrate and for minerals. Kuka bark
      (Adansonia digitata) given to infants to increase weight gain was high in fat,
      calcium, copper, iron, and zinc. Cediya (Ficus thonningii), dorowa (Parkia
      biglobosa) and zogale (Moringa oleifera) were good sources of protein and fat and
      excellent sources of calcium and iron or copper and zinc. Fruits, leaves, and
      nuts of aduwa (Balanites aegyptiaca) were widely used during the dry season and
      during drought. Edible wild species available during the wet season generally
      were inferior in energy and micronutrient mineral content compared to dry season
      plants. Fruits commonly eaten by children were poor sources of protein and
      minerals but rich in carbohydrate and fiber. Tsamiya seeds (Tamarindus indica)
      were good sources of zinc and used to make dawwa (porridge) commonly consumed
      during pregnancy. Kirya seeds (Prosopos africana) contained the highest zinc
      concentrations. Shiwaka leaves (Veronia colorate) consumed by pregnant women to
      increase breastmilk production and to expel intestinal worms, were high in fiber,
      phosphorus, magnesium, manganese, and were adequate sources of calcium.

PMID- 10945117
TI  - Vitamin D: should the supply in the Danish population be increased?
AB  - A working group was established to evaluate the need for an increased vitamin D
      intake in the Danish population. Vitamin D is primarily important for calcium
      homeostasis, calcium absorption in the intestine and calcium content in bones,
      and thereby for the strength of the bones. Only a few foods provide vitamin D and
      the intake in the Danish population is low compared to the recommendation.
      However, vitamin D is also produced by the skin from solar exposure. How much
      vitamin D is provided this way is not known but it is said to be the most
      important source. Measures of vitamin D status and clinical signs of vitamin D
      status are therefore important when assessing the possible need for increased
      vitamin D intake. Measures of vitamin D status have shown a low status in the
      elderly but not in the young. More than 50% of nursing-home residents have low
      blood vitamin D levels and many have biochemical signs of osteomalacia. Vitamin D
      deficiency increases the risk of osteoporosis. In Denmark, for instance, 13,000
      admissions each year are caused by hip fractures alone, almost all among elderly
      people. Dark-skinned women often constitute a problem with respect to vitamin D
      sufficiency because of reduced production from the skin secondary to extensive
      covering, skin pigmentation and many hours spent indoors. It is concluded that
      the elderly and dark-skinned (veiled) women will benefit from an increased
      vitamin D supply. Four strategies to increase vitamin D supply were considered:
      dietary changes, increased solar exposure, dietary supplements with vitamin D and
      food fortification with vitamin D. It is concluded that the best solution is to
      recommend dietary supplements with vitamin D to elderly over 65 years, dark
      skinned and veiled women and people who, because of disease, are unable to spend
      time outdoors.

PMID- 10945118
TI  - Why have we been more successful in reducing tobacco use than violent crime?
AB  - Tobacco control efforts have been associated with a significant reduction in the
      prevalence of tobacco use in the United States. Efforts to reduce the incidence
      of violent crime have been much less successful. This paper argues that progress
      on tobacco control stems from the existence of a clear, empirically based, and
      widely understood analysis of the tobacco problem that articulates (a) the harms
      associated with its use, (b) the causes of tobacco use, and (c) the programs and
      policies that could reduce tobacco use. This analysis has guided the development
      of a network of social organizations that have been advocating for policies and
      programs that are reducing tobacco use. In contrast, there is not a widely
      shared, cogent, and empirically based analysis of the problem of violent crime.
      As a result, efforts to combat violent crime are fragmented and it has proven
      difficult to generate support for preventive programs and policies. Substantial
      empirical progress has been made, however, on how violent crime could be
      prevented. That evidence is reviewed. It is argued that the articulation of this
      evidence is a critical first step for achieving widespread reduction in the
      incidence of violent crime. Communication of that evidence to audiences that
      matter will require that behavioral scientists become better organized to
      advocate for the adoption of empirically supported practices.

PMID- 10945119
TI  - The role of referent and expert power in mutual help.
AB  - This study explored the roles of referent power (i.e., influence based on sense
      of identification) and expert power (i.e., influence based on knowledge and
      expertise) in Schizophrenics Anonymous (SA), a mutual-help group for persons
      experiencing a schizophrenia-related illness. The study describes SA
      participants' experience of referent and expert power with SA members, SA
      leaders, and with mental health professionals. It also examines whether or not
      referent and expert power ascribed to fellow SA participants predicts the
      perceived helpfulness of the group. One hundred fifty-six SA participants were
      surveyed. Participants reported experiencing higher levels of referent power with
      fellow SA members and leaders than with mental health professionals. They
      reported higher levels of expert power for mental health professionals and SA
      leaders than for SA members. The respondents' ratings of their SA group's
      helpfulness was significantly correlated with ratings of referent and expert
      power. Although expert power was the best independent predictor of helpfulness, a
      significant interaction between referent and expert power indicated that when
      members reported high referent power, expert power was not related to
      helpfulness. These results are interpreted to suggest that there are multiple
      forms of social influence at work in mutual help.

PMID- 10945120
TI  - Mutual help groups, perceived status benefits, and well-being: a test with adult
      children of alcoholics with personal substance abuse problems.
AB  - A field experiment was conducted to examine the potential effects of mutual help
      group participation on perceived status benefits, depression, and substance use
      among adult children of alcoholics (ACOAs) with personal substance abuse
      problems. Participants were randomly assigned to attend either ACOA-specific
      mutual help group meetings or substance abuse education classes during the
      initial month that they were enrolled in a residential treatment program for low
      income substance abusers. Analyses were based on assessments made at baseline, a
      1-month posttest, and a 6-month follow-up. Results indicated that participation
      in the mutual help group promoted perceived status benefits, which in turn led to
      reductions in depression and substance use. These findings have clear
      implications for consumers of ACOA groups and can inform research on the social
      psychological underpinnings of different types of mutual help groups.

PMID- 10945121
TI  - Let's ask the homeless people themselves: a needs assessment based on a
      probability sample of adults.
AB  - A probability sample of 301 homeless adults from Buffalo, NY, was followed over 6
      months to document the utilization of a variety of community services, examine
      services desired, and identify factors associated with service utilization,
      preference, and satisfaction. The following needs were all rated as at least
      equally important as the need for affordable housing: safety, education,
      transportation, medical/dental treatment, and job training/placement (most of
      these needs were also rated as difficult to obtain). Needs for formal mental
      health and substance abuse services were rated as relatively unimportant and easy
      to obtain, and for those who actually used them, respondents were often
      dissatisfied with them. Of 16 predictor variables examined in multivariate
      analyses, several showed consistent relationships with subsequent service use,
      preference, and satisfaction. Younger adults, persons of color, those with
      dependent children, and persons having fewer social supports reported less
      service utilization, less satisfaction with services received, different
      perceived needs for particular services, and/or greater difficulty obtaining
      services.

PMID- 10945123
TI  - Psychometric properties of the Multidimensional Scale of Perceived Social Support
      in urban adolescents.
AB  - The psychometric properties of the Multidimensional Scale of Perceived Social
      Support (MSPSS) were investigated in 222 urban, largely African-American
      adolescents (68%). High internal consistency was demonstrated, and factor
      analysis confirmed the three subscale structures of the MSPSS: family, friends,
      and significant other. Correlations with a family caring scale supported the
      discriminant validity of the Family subscale. These results confirm the
      reliability, validity, and utility of the MSPSS with an urban, largely African
      American adolescent sample. Implications of the findings are discussed.

PMID- 10945122
TI  - Antecedents of physical and sexual victimization among homeless women: a
      comparison to homeless men.
AB  - Homeless women experience extensive health risks including physical and sexual
      victimization. Few studies that have gathered information on homeless persons
      have reported results separately for women or have compared them directly with
      men. Research that both investigates antecedents of victimization among homeless
      women and compares them to those for men is necessary to determine whether
      prevention efforts must be different for each group. We investigated potential
      antecedents of recent (past 30 days) physical and sexual victimization in a
      probability sample of 394 homeless women and compared findings to those for 1159
      homeless men. As hypothesized, mental disorder, substance dependence, and
      engaging in economic survival strategies significantly predicted victimization
      among homeless women. With few dissimilarities, these characteristics also
      predicted victimization among homeless men. Although differences in the needs and
      experiences of homeless women and men must be recognized, both women and men
      require assistance to establish and maintain safe residences, treatment of any
      substance use and mental disorder, and alternatives to economic survival
      strategies that place them at risk for victimization.

PMID- 10945124
TI  - An ethicist's commentary on whether a technician should administer preanesthesia
      without a veterinary examination.

PMID- 10945125
TI  - A field efficacy evaluation of emamectin benzoate for the control of sea lice on
      Atlantic salmon.
AB  - This study evaluated the efficacy of emamectin benzoate, 0.2% aquaculture premix,
      against sea lice on Atlantic salmon in eastern Canada. Salmon pens received
      either emamectin benzoate, orally, in feed at 50 micrograms/kg body weight/day
      for 7 consecutive days, or the same diet with no added medication. The site
      veterinarian had the option of administering a bath treatment with azamethiphos
      to any pen in the trial. The mean number of lice per fish was lower (P < 0.05) in
      the experimental group when measured 1, 3, 4, and 6 weeks after the start of
      medication. Treatment efficacy was 70%, 88%, 95%, and 61%, respectively. Three
      azamethiphos bath treatments were applied to each control pen during the trial,
      while the treatment pens received no bath treatment. No gravid female parasites
      were observed on any fish in the treatment group, while these life stages were
      observed on fish in the control group. Orally administered emamectin benzoate was
      palatable and highly effective for control of sea lice on salmon.

PMID- 10945126
TI  - A gel delivery system for coccidiosis vaccine: uniformity of distribution of
      oocysts.
AB  - A patented gel delivery system being used to deliver coccidiosis vaccine to
      poultry hatchlings is assessed. For effective vaccination, the coccidial oocysts
      must be uniformly suspended before exposure to birds. The uniformity of
      distribution within the gel was evaluated by incorporating a culture of chicken
      gut flora into gel sausages, placing sections of the sausage on culture plates,
      determining the appearance and distribution of bacterial colonies on culture
      plates after incubation, and verifying by cell counts. The uniformity of
      distribution of similarly prepared coccidial oocysts was verified by infecting
      birds with 40,000 Eimeria tenella oocysts delivered via the gel. Gel-inoculated
      birds were compared with control birds inoculated PO with 40,000 oocysts
      suspended in water by using cecal lesion scores. Both the appearance and colony
      counts of chicken gut flora from the gel were uniform. The standard deviation in
      the lesion scores for the gel-inoculated group and the water-inoculated groups
      were 0.51 and 0.69, respectively. The results indicate that a gel delivery system
      can provide uniform distribution of live organisms and vaccine agents to birds.

PMID- 10945127
TI  - The effect of animal health products on the formation of injection site lesions
      in subprimals of experimentally injected beef calves.
AB  - Two hundred and twenty beef calves were used in an experimental study to
      determine the occurrence of injection site lesions at slaughter (15 to 18 months
      of age) following subcutaneous and intramuscular injection of various products
      into the top hip (top butt), thigh (round), and neck or rib of calves at birth,
      branding, or weaning. Products tested were: 2 different preparations of selenium;
      a 2-way, a 7-way, and an 8-way clostridial bacterin; 2 combination 7-way
      clostridial and Haemophilus somnus bacterins; 2 H. somnus bacterins; 2 different
      4-way modified-live viral respiratory vaccines; a 4-way killed viral and H.
      somnus vaccine; and penicillin, florfenicol, ceftiofur, trimethoprim-sulfa, and
      tilmicosin. The occurrence of lesions, number of steaks affected with lesions,
      the trim weight of lesions, the histological class of lesions, and the estimated
      economic losses are described. Generally, products administered subcutaneously in
      the neck produced minimal tissue damage and economic losses.

PMID- 10945128
TI  - Clinical observations of the treatment of canine perianal fistulas with topical
      tacrolimus in 10 dogs.
AB  - Tacrolimus ointment, a potent immunosuppressive medication, was evaluated for
      efficacy in the treatment of perianal fistulas in dogs. Ten dogs with perianal
      fistulas were treated with topical tacrolimus ointment once to twice daily for 16
      weeks. Full healing of the fistulas occurred in 50% and was noticeably improved
      in 90% of dogs.

PMID- 10945129
TI  - Epitheliotropic lymphoma in a dog.
AB  - Despite treatment with steroids, nodular areas of alopecia and erythematous skin
      lesions persisted in a 9-year-old Irish water spaniel with discoid lupus.
      Epitheliotropic lymphoma was diagnosed by skin biopsy.

PMID- 10945130
TI  - The CVMA animal abuse position--how we got here.

PMID- 10945131
TI  - Pet insurance--a benefit for key employees?

PMID- 10945132
TI  - Pet insurance--essential option?
AB  - As Hawn (2) says, "insurance is about risk and peace of mind." She reports that
      the American Humane Society supports pet insurance because companion animals are
      able to be treated for disease or accidents that are life-threatening where,
      otherwise, they would have been euthanized. For veterinarians, she suggests that
      pet insurance allows them to practice veterinary medicine "as if it were free."
      It is inevitable that pet insurance will grow as a recourse for veterinary fees.
      This may be a savior to some families whose budget is stretched to the limit at a
      critical moment in the health care of their cherished pet. We in the veterinary
      profession have an advantage over other professions. We have seen the good, the
      bad, and the ugly of insurance, as it applies to human health and dental care. If
      we work hand-in-hand with our own industries, collectively we may be able to
      develop a system that wins for everyone, with fees that allow practice to thrive
      and growth strategies that accommodate new treatment and diagnostic modalities,
      as well as consistent and exemplary customer service. The path ahead is always
      fraught with bumps and potholes. We can be a passive passenger and become a
      victim of the times or an active driver to steer the profession to a clearer
      route. Pet insurance is but one of the solutions for the profession; the others
      are a careful assessment of our fees--charging what we are worth, not what we
      think the client will pay; business management; customer service; leadership of
      our health care team; lifelong learning; and more efficient delivery systems. Let
      us stop being a victim, stop shooting ourselves in the professional foot, and
      seize the day!

PMID- 10945133
TI  - Diagnostic ophthalmology. Primary glandular orbital epithelial neoplasm in a dog.

PMID- 10945134
TI  - Sertraline in the treatment of anxiety disorders.
AB  - Sertraline was first developed and approved for the treatment of depression.
      However, considerable research has been conducted on its use in anxiety
      disorders. This paper reviews the data emerging from controlled and open trials
      of the use of sertraline in anxiety disorders. Sertraline has been tested
      extensively in the treatment of panic and obsessive-compulsive disorders. Less
      extensive testing has been completed on social phobia and post-traumatic stress
      disorder. The reviewed studies show that sertraline is an effective and well
      tolerated treatment of all of these disorders. A comparison of sertraline with
      other pharmacotherapeutic options shows it to be at least equivalent to other
      medications for anxiety disorders.

PMID- 10945135
TI  - Panic disorder and perceived parental rearing behavior investigated by the
      Japanese version of the EMBU scale.
AB  - Although recent studies have found dysfunctional parental rearing behaviour is
      associated with certain aspects of psychopathology of panic disorder (PD), the
      results are not in complete agreement. By using a translated Japanese version of
      the EMBU (Egna Minnen Betraffande Uppfostran), we investigated the parental
      rearing behavior perceived by 103 normal subjects, 71 PD patients with
      agoraphobia, and 32 PD patients without agoraphobia. The PD patients scored both
      parents as more rejecting and overprotective than did the controls. However,
      subgroup analysis showed that the patients with agoraphobia reported
      significantly more rejection from both parents and less emotional warmth from
      mothers, while the patients without agoraphobia, by contrast, reported more
      overprotection from both parents and more favouring subject from fathers than did
      the controls. Interestingly, these results were consistent with those documented
      in the Western literature, which reported "affectionless control" as a parenting
      style in PD, and, furthermore, indicated a cross-cultural similarity of parental
      rearing factor. In addition, it was suggested that a lack of care might be
      associated with the development of agoraphobia in Japan.

PMID- 10945136
TI  - Clinical correlates of obsessive compulsive disorder in children and adolescents
      referred to specialized and non-specialized clinical settings.
AB  - The objective of this study was to assess the extent of referral bias by
      comparing children and adolescents with Obsessive Compulsive Disorder (OCD)
      ascertained through a specialized pediatric OCD and a general child psychiatry
      clinic. Subjects were juveniles meeting DSM-III-R and DSM IV criteria for OCD
      referred to a general pediatric psychopharmacology clinic and to a specialized
      OCD clinic within the same academic medical center. Subjects were evaluated
      clinically and with structured diagnostic interviews using the Kiddie SADS-E. OCD
      was identified in 8.6% of the general psychiatry clinic subjects. The only
      differences between ascertainment sources in clinical or sociodemographic
      characteristics of OCD subjects were higher rates of social phobia and ADHD in
      the non-specialized clinic, while specialty clinic subjects had a greater
      lifetime severity of OCD and were more likely to have received treatment of their
      OCD. Because we found limited evidence for referral biases, our results suggest
      that findings from studies using either of these sources may generalize to the
      other. It also suggests that pooling subjects from the two sources is justified.
      Nevertheless, because some group differences did emerge, researchers should
      acknowledge referral bias as a potential limitation of their work.

PMID- 10945137
TI  - Verbalization and imagery during worry activity.
AB  - This study examined a model of worry as verbal activity that suppresses imagery
      and autonomic fear. The effects of emotional imagery vs. verbalization upon worry
      and fearfulness of an impending public speaking situation were assessed in 54
      public speaking anxious participants who were categorized as worriers. Randomly
      assigned groups that processed the impending public speaking task either verbally
      or imaginally were compared to a group that received no processing instructions.
      Subjective distress was measured throughout the study. Results revealed partial
      support for the hypotheses that proportions of verbal thought and imagery shift
      upon threat presentation and a mitigation of fear habituation with verbalization.
      However, interpretation of between-group differences was complicated because the
      groups did not report consistent or complete adherence to cognitive processing
      instructions. Methodological and design implications for future investigations in
      this area are discussed.

PMID- 10945139
TI  - Stability of subclinical obsessive compulsive disorder in college students.

PMID- 10945138
TI  - Differentiation of depression and PTSD symptoms in combat veterans.

PMID- 10945140
TI  - Acute stress disorder and subsequent post-traumatic stress disorder in a group of
      exposed disaster workers.

PMID- 10945141
TI  - Pathological gambling behaviour: emergence secondary to treatment of Parkinson's
      disease with dopaminergic agents.
AB  - We present a case in which the use of low dose risperidone (a potent D2 and 5-HT2
      antagonist) was successful in controlling gambling behaviour secondary to
      dopamine agonist treatment of Parkinson's disease. Pharmacotherapeutic management
      of pathological gambling secondary to medical causes deserves further study.

PMID- 10945142
TI  - Risperidone in the treatment of acute stress disorder in physically traumatized
      in-patients.
AB  - Although symptoms of acute stress disorder or PTSD in the aftermath of physical
      trauma may be a reason for psychiatric referral, little has been written on the
      management of patients in this context. We report the possible benefit of
      risperidone, an atypical antipsychotic, in 4 cases where flashbacks were reported
      in patients hospitalized for the treatment of physical trauma.

PMID- 10945143
TI  - [Fatty acids and beta cells].
AB  - In type 2 diabetes mellitus, insulin secretory deficiency is an important process
      linking asymptomatic insulin resistance and diabetes. Fatty acids could play a
      role in the reduction of beta cell insulin secretion. On a short term basis (< 24
      h), fatty acids stimulate glucose-dependent insulin secretion through an increase
      of ATP availability (due to acyl-CoA mitochondrial oxidation) and an
      extramitochondrial diacylglycerol and inositol tri phosphate (IP3) production
      (which stimulate insulin-containing granule exocytosis). Such effects were
      observed in human both in vitro and in vivo. By contrast, a chronic exposure (>
      24 h) of beta cells to fatty acids leads to a reduction in glucose-dependent
      insulin secretion. Current explanation relies in the effect of fatty acids on
      beta cell gene expression through PPARs (peroxysome proliferator activated
      receptor). Thus, in rodents, fatty acids can increase the expression of carmitine
      palmitoyl transferase gene (CPT-1, the key enzyme involved in fatty acid
      internalization in mitochondria) while reducing the gene expression of acetyl
      carboxylase (this enzyme synthesis malonyl CoA, which inhibits fatty acid
      oxidation). Thus, a chronic exposure to fatty acids will preferentially
      distribute these nutrients towards mitochondria (as malonyl CoA is reduced and
      CPT-1 is increased), which in turn reduces their extramitochondrial metabolism as
      well as IP3 production that is needed for secretory granule exocytosis. Finally,
      in Zucker Fatty rat, diabetes is associated with a triglyceride accumulation in
      beta cells. This is correlated with a reduction in insulin secretion and an
      increase in cellular apoptosis phenomena. Thiazolidinediones prevent
      intracellular lipid accumulation and delay diabetes. The prevention of
      lipotoxicity could represent a new therapeutic strategy to preserve insulin
      secretion in type 2 diabetic patients.

PMID- 10945144
TI  - [Metabolic difference between visceral fat and subcutaneous abdominal fat].
AB  - Obesity stands as a public health issue. Obesity prevalence is increasing
      throughout every industrialized country. Android obesity is linked with an
      increased cardiovascular mortality and with type 2 diabetes mellitis, thus
      calling for an early management of this disease. Several studies showed a
      significant association between an android fat distribution and an increased
      cortisol secretion, raising the still debated question of a causal relationship
      between the development of android obesity and hypercorticism. Moreover, android
      obese subjects exhibit reduced plasma testosterone and growth hormone levels,
      meaning complex hormonal abnormalities in these subjects. Current hypotheses
      suggest that android fat distribution depends on the association of these
      hormonal abnormalities. Android obese patients have supranormal free fatty acid
      plasma concentrations. Visceral fat tissue, through its portal drainage, could be
      an important source for free fatty acids that may exert complex metabolic
      effects: involvement in hepatic lipogenesis, increase in hepatic neoglucogenic
      flux, reduction in insulin metabolic clearance and involvement in peripheral
      insulin resistance through a competition mechanism described by Randle. Technics
      in vitro (isolated adipocytes) and in vivo in human (labelled fatty acid flux)
      showed that visceral fatty acid flux was increased in obese patients and
      subcutaneous adipose tissue, as opposed to common opinion, was also involved in
      free fatty acid pool in obese patients. Thus, visceral obesity and diabetes could
      be linked through an enhanced fatty acid availability from adipose tissues
      (visceral and subcutaneous) in otherwise genetically type 2 diabetes-prone
      individuals.

PMID- 10945145
TI  - [Type 2 diabetes and beta cell apoptosis].
AB  - Type 2 diabetes mellitus features an asymptomatic insulin resistance phase
      preceding the onset of diabetes. Hyperglycemia occurs when a relative insulin
      deficiency appears, meaning that beta cell secretory dysfunction is a key element
      in type 2 diabetes pathophysiology. So far, insulin secretion deficiency is
      explained by pancreatic beta cell "exhaustion" phenomena. Recent data suggest
      that apoptotic mechanisms could explain insulin deficiency through a reduction in
      the absolute pancreatic beta cell number. Psammomys obesus (sand rat) is an
      animal model for type 2 diabetes mellitus, initially characterized by
      hyperinsulinism followed by insulin deficiency linked with a reduction in the
      number of pancreatic beta cells. Transition to diabetes can be observed following
      changes in usual lifestyle of the sand rat. In the desert, caloric intake is low
      and physical expenditure is heavy. In the laboratory, animals turn diabetic as
      early as 4 days following a high calorie diet. At a later stage, diabetes is
      irreversible and animals die from diabetic ketoacidosis. beta cell apoptosis rate
      is low in non diabetic animals and increases 14-fold by 20 days after diabetes
      onset. At this stage, cells undergoing apoptosis can be observed, coexisting with
      necrotic cells without any insulitis. Similar results were obtained in vitro in
      isolated pancreatic islets that were exposed to increasing glucose
      concentrations, suggesting that chronic hyperglycemia plays a role in the onset
      or the deterioration of the process. However, precise mechanisms of apoptosis in
      this case remain poorly understood. Aminoguanidin does not prevent beta cell
      apoptosis in vitro, suggesting that advanced glycation products or NO production
      are not involved in this beta cell destruction process. Similar mechanisms
      secondary to hyperglycemia could play a role in the diabetes process in man and
      explain the marked insulin secretory deficiency that is sometimes observed in
      these patients. In addition to its preventing role on diabetes complication, the
      obtention of normoglycemia could help maintaining beta cell function.

PMID- 10945146
TI  - [Update on the epidemiology of obesity and type 2 diabetes in France].
AB  - The INSEE national surveys in 1980 and 1991, and the OBEPI study in 1997, allowed
      to study the prevalence of overweight and obesity in France, as well as its
      increase during these past years. The number of adult obese individuals remained
      stable between 1980 and 1991. The 1997 estimation suggests a moderate increase.
      By contrast, the number of obese children has increased between 1980 and 1991,
      whatever the level of study of the mother. Several diseases are strongly linked
      with obesity, such as hyperuricemia, hypertension, coronary heart disease,
      diabetes mellitus. Thus the declared prevalence of diabetes is 2% when BMI ranges
      from 18.5 to 25 kg/m2, and reaches 20% at a BMI > 34 kg/m2 with age ranging 40-70
      years old. The presence of obesity during childhood is also correlated with an
      increased mortality, with an enhanced prevalence of coronary heart disease,
      hyperuricemia, colon cancer in men, and joint disease in women during adulthood.
      An increase in the prevalence of diabetes is expected in the near future:
      demography, as children born after the war will reach age of 55-75, the lowering
      of glycemic threshold for the diagnosis of diabetes, increased prevalence of
      obesity are the main explanations. Our health care system will need to evolve in
      order to deal with this increased number of patients, and measures have been
      recently set for that purpose.

PMID- 10945147
TI  - [Use of insulin therapy in France. Results of the scheme survey].
AB  - Insulin therapy was analysed among 1260 type 1 or type 2 diabetic patients during
      a national transversal survey. A total of 934 MDs, mostly diabetologists, agreed
      to participate in this study, among which about half sent questionnaire forms
      back. The number of different insulin therapy schemes was as high as 36, glucose
      control was not related with the number of shots. Usual management regarding
      injection and glucose self-monitoring is described in this population which
      mostly relies on a diabetologist follow-up. One third of patients featured an
      HbA1c < 7.5%. Overall, glucose control remains unsatisfactory and too many
      patients do not benefit from an optimized insulin therapy.

PMID- 10945148
TI  - [News from UKPDS].
AB  - Risk factors present in type 2 diabetic patients at the time of their inclusion
      in the study were related with the occurrence of some complications. Thus,
      relative risk for coronary heart disease is 1.57 when HbA1c is > 7.5%, 1.41 when
      LDL-Cholesterol is > 3.89 mmol/l, these factors are not involved in the
      occurrence of cerebral stroke. Blood pressure and HbA1c were monitored throughout
      the study and could have been significantly correlated with the occurrence of
      micro- and macroangiopathy, with a linear-type and even exponential
      (HbA1c/retinopathy) relationship and a synergistic interaction between these 2
      parameters. A treatment allowing a 0.9% decrease of HbA1c and a 10 mmHg decrease
      of systolic blood pressure is associated with a reduction of complications, more
      or less important than that expected from the epidemiological analysis of data.
      Several therapeutic strategies ensue from these observations.

PMID- 10945149
TI  - [Psychopathology of obesity. Therapeutic contract].
AB  - Multiple mechanisms lead to the establishment and maintenance of obesity. A
      better understanding and analysis of theses factors should help to design
      improved therapies. The therapeutic constract is based upon the hypothesis that
      many subjects have an "empathic" type of psychological structure and builds a
      physician-patient relationship allowing the patient to be supported during its
      dietary effort and to feel confident enough to express his difficulties, and the
      physician to better understand his patient and anticipate on an eventual relapse.
      The ideal weight notion is a key element, as it should not be considered as an
      established target based upon standards, but rather be progressively adapted
      between physician and patient.

PMID- 10945150
TI  - [Role of bariatric surgery in the obese diabetic].
AB  - Bariatric surgery can be proposed to address severe obesity associated with
      comorbid conditions, when medical treatment has failed. Three surgical techniques
      are currently available, including 2 using coelioscopy. Short term results are
      encouraging regarding weight loss, which is linked with a reduction in comorbid
      conditions such as glucose intolerance. The number of studies is too low to
      assess long term results. Surgery in obese diabetic patients rapidly improves
      insulin resistance, thus allowing to reduce antidiabetic treatment. However these
      positive effects should be balanced with surgery-linked complications, therefore
      gastroplasty indications should be thoroughly examined.

PMID- 10945151
TI  - [Drug treatment of obesity and type 2 diabetes].
AB  - Drug therapy of obesity (DTO) has not been extensively used in diabetic patients
      so far, although excessive adipose mass largely contributes to insulin resistance
      which characterizes this disease together with insulin secretion failure.
      Orlistat is the sole currently available treatment, but several other new
      treatments are under investigation, such as sibutramine already marketed in other
      countries. Both drugs were found to be efficient in long term studies (1 year).
      However it is puzzling to note that weight loss induced by the drug as well as
      during placebo treatment is less pronounced in diabetic patients as compared with
      non diabetic subjects. Short term studies had already documented a lower response
      to DTO in diabetic patients by 2-fold. The reasons for this weight loss
      resistance in diabetics under DTO remain unclear and could be linked with
      metabolism. A weight loss > or = 5% initial body weight is required to obtain a
      significant lowering of HbA1c. Weight variations (weight delta > or = 5-10%
      initial weight) and results on glucose control (HbA1c delta > or = 0.5% after 3
      to 6 months, or fasting blood glucose delta > or = 1 mmol/l within a few weeks)
      allow to define good DTO responders which should preferentially be eligible for
      this treatment. A decisional diagram is suggested.

PMID- 10945152
TI  - [Mechanisms for weight gain during blood glucose normalization].
AB  - Secondary failure to dietary and maximal oral treatment leads to insulin therapy
      in type 2 diabetic patients. However, weight gain is a frequent side effect of
      insulin therapy in these patients. Mechanisms for this weight gain are complex.
      Insulin 1) reduces glycosuria and its caloric expenditure; 2) stimulates the
      stockage of fatty acids into triglycerides in adipose tissue, thus favoring an
      increase in adipose mass; 3) yields a positive nitrogen balance through an
      inhibition of muscle proteolysis, thus favoring an increase in lean mass. Most
      studies report an average 6 kg weight gain during the first year following the
      initiation of insulin therapy in type 2 diabetic patients. Analysing body
      composition variations shows that weight gain results both from an increase in
      fat mass (mean 63%) and an increase in lean mass (mean 37%). Preexisting obesity
      does not influence this weight gain. Finally, the 10 year-follow up of UKPDS
      showed a beneficial effect of insulin therapy on microangiopathy prevention,
      without increasing cardiovascular mortality as compared with type 2 diabetic
      patients on oral treatment. Thus, while weight gain seems mandatory, it should
      not refrain from initiating insulin therapy in poorly controlled type 2 diabetic
      patients, as its expected beneficial effects on the prevention of microangiopathy
      seem well established.

PMID- 10945153
TI  - [Very-low-calorie-diets: is there a place for them in the management of the obese
      diabetic?].
AB  - It is well-recognized that standard caloric restrictions (1500 kcal/day) are
      usually poorly effective in achieving weight losses in overweight type 2 diabetic
      patients. For that reason very-low-calorie-diets (VLCDs) were developed as a mean
      for initiating or accelerating weight reduction. Short-term studies indicate that
      VLCDs result generally in weight losses that are three times greater than those
      obtained with standard low-calorie-diets. Fasting blood glucose values are
      improving in parallel to weight losses and in many patients the improvement in
      glycemic control is better than that expected from the magnitude of weight
      losses. However the results are rather disappointing after several months or
      years of follow-up. For example it has been demonstrated that weight regain can
      be observed as soon as the patient is shifted to a refeeding or maintenance
      dietary program at the end of the VLCD period. Long-term results on glycemic
      control and body weight reduction are generally similar with standard low-calorie
      diets and with VLCDs, the final results depending on the magnitude of weight loss
      whatever the prescribed diet. At short-term the VLCDs can be helpful first for
      initiating weight losses and second for sensitizing the patient to the potential
      benefits of complying to dietary measures.

PMID- 10945154
TI  - [News of Humalog and Humalog mix in the treatment of type 2 diabetes].
AB  - Fast-acting insulin analog (lispro insulin), as well as slow/fast-acting analog
      mixtures (NPL-lispro insulin) allow a better control of postprandial glycemia in
      type 1 and type 2 diabetic patients (35% mean reduction in area under curve for
      postprandial glycemia, 2 mmol/l reduction in postprandial glucose peak), as
      compared with regular insulin or conventional mixtures of NPH and regular
      insulin. Analog pharmacokinetics allow to procede to insulin injection
      immediately before meal, which is convenient for the patients. When used alone,
      lispro insulin has no impact on basal glycemia, whereas twice daily injections of
      NPL-lispro mixtures allow a 1.8 mmol/l mean reduction of basal glycemia, as
      compared with conventional mixtures, meaning a more specific effect of NPL
      intermediate insulin. Other premeal blood glucose levels (lunch and dinner) are
      not improved by lispro insulin. Most studies did not establish a clear reduction
      in HbA1c with insulin analogs. When this is the case, this reduction averages
      1.5% and could be more frequently observed in studies dealing with type 2
      diabetic patients. Finally, the reduced incidence of delayed hypoglycemic
      episodes, which is one of the most attractive effects of insulin analogs, was
      only reported in a minority of studies. Surprisingly, the reduction of
      hypoglycemia incidence with analogs was more frequently reported in type 2
      diabetics than in type 1 patients. Thus fast-acting insulin analogs feature
      interesting characteristics, noteworthy immediate premeal injection and a better
      postprandial glucose control. However, it is established that the determination
      of diabetes complications (particularly microangiopathy) mostly relies on average
      glucose control and not solely on postprandial glycemia. Indeed, most studies
      suggest that insulin analogs are at least as efficient as conventional insulins
      on HbA1c, but possibly not more.

PMID- 10945155
TI  - [The study of central nervous information processing with transcranial magnetic
      stimulation].
AB  - In cognitive neuroscience different methods are used to study central nervous
      information processing. Transcranial magnetic stimulation (TMS) is a non
      invasive, well tolerated technique to interfere with cortical neuronal activity
      with high temporal and fair spatial resolution. In the past 10 years the use of
      TMS expanded from its application as a diagnostic routine procedure in neurology
      to the study of various cognitive functions. In this paper the physical and
      technical aspects of TMS and studies on the effects of single pulse versus
      repetitive TMS in the motor cortex are reviewed. Then, research on visual
      perception and attention is presented and studies on higher cognitive functions,
      such as speech, memory, and emotions are discussed.

PMID- 10945156
TI  - [Diseases of phospholipid metabolism as possible pathogenetic factors in
      schizophrenia. Current findings and critical evaluation].
AB  - During the last few years analyses of the lipidmetabolism have been performed on
      schizophrenic patients. Anabolic and katabolic metabolite-concentrations from
      blood and cell samples have been measured. By means of new investigation
      techniques, such as 31P-magnetic-resonance-spectroscopy, it is nowadays even
      possible to determine membrane metabolites non-invasively in vivo. Arachidonic
      acid deficits in peripheral cell membranes, turnover of phosphodiesters in the
      brain, increased phospholipase A2 (PLA2)-activity in serum and blood cells,
      disturbed niacin-response and abnormalities of the PLA2-gene are summarised as
      phospholipid-membrane-hypothesis of schizophrenia. Although there is some
      evidence for correlations between those findings and psychotic symptoms, the
      connection to the pathogenesis of schizophrenia still has speculative character.
      Furthermore it has to be confirmed that peripheral biochemical findings acquired
      in schizophrenics are transferable to the metabolism of the central nervous
      system. Actual results of enzyme and metabolite measurements reported in
      literature and current findings of our own 31P-MR-spectroscopic studies are
      surveyed and summarised. To point out possible connections between the
      phospholipid-metabolism of the central nervous system and of peripheral blood
      cells, systemic approaches are considered.

PMID- 10945157
TI  - [Open studies in comparison to controlled studies in testing of neuroleptics].
AB  - OBJECTIVE: Due to methodological reservations, results concerning the efficacy of
      neuroleptics in open trials are often regarded with doubt. Until now, there are
      nearly no studies comparing findings of controlled double-blind with those of
      open trials. Aim of this study was to investigate if results of an open or double
      blind approach differ and hereby to gain information about the validity of open
      trials. METHODS: After a literature research, five neuroleptics were identified
      for which at least 3 open and 3 double-blind trials exist which met the inclusion
      criteria and from which either the reduction of the BPRS (Brief Psychiatric
      Rating Scale)-score or the response rate could be determined. RESULTS: There were
      no differences in the reduction of the BPRS-score or response rate for all 5
      neuroleptics between open and double-blind trials. Furthermore, the efficacy of
      all 5 neuroleptics was comparable. CONCLUSIONS: Double-blind controlled studies
      are essential in the investigation of new compounds. But results of
      methodologically well performed open studies are valid and deserve more
      attention. Preceding open trials may help in the design of double-blind studies.

PMID- 10945158
TI  - [Clinical characteristics of patients with tardive dyskinesias].
AB  - Although there is a great number of studies on the relationship between tardive
      dyskinesia and patient characteristics, too often their validity is impaired by
      the lack of operationalized criteria for the description of patients and signs.
      Reliable phenotyping is of utmost importance for linking clinical data with data
      from methods in neurobiology or molecular genetics. 241 patients with the DSM IV
      diagnosis "schizophrenia" or "schizoaffective disorder" were examined with the
      instruments SADS-L, OPCRIT, BPRS and PANSS. Motor phenomena were analyzed on 2
      separate days within 3 months with the scales TDRS, AIMS, SAS, BAS. Tardive
      dyskinesia was diagnosed following the research criteria of Schooler and Kane.
      Lifetime medication with neuroleptics and anticholinergic drugs was assessed
      quantitatively. RESULTS: 97 out of 233 patients (= 41.6%) displayed persistent
      tardive dyskinesia. In univariate analysis, significant associations were found
      between tardive dyskinesia and the following independent variables (higher values
      means greater risk): Age (p = 0.0001), years from onset of the disorder (p =
      0.001), total length of stay in hospital (p = 0.001), PANSS (single scales and
      sum score) (p = 0.0001), total amount of neuroleptics expressed as CPZ
      equivalents (p = 0.004). Logistic regression analysis showed that only the
      variables "age" and "negative symptoms" expressed as score on the PANSS negative
      subscale showed an association with tardive dyskinesia that could not be
      explained by covariation with other variables. The same results were found when,
      instead of the dichotomous variable "tardive dyskinesia yes/no" the associations
      with the TDRS score were analyzed. Future research should aim to approach the
      neurobiological correlates of "age" and "negative symptoms" in relationship to
      tardive dyskinesia.

PMID- 10945159
TI  - [The migraine of Immanual Kant].
AB  - The German philosopher Immanuel Kant (1724-1804) suffered, since his forties,
      from a migraine with aura which showed a significant exacerbation in his
      seventies, coinciding with the onset of symptoms of a senile dementia of
      Alzheimer's type. Recorded symptoms of Kant's migraine include recurrent
      scintillating scotomas, one episode of diplopia, two episodes of complete
      amaurosis and frequent headaches described as oppressions of the head. The said
      symptoms of Kant's migraine can be traced not only in his letters and in accounts
      of his contemporary biographers, but also in the philosopher's published work.

PMID- 10945160
TI  - Cryptophycin 52 and cryptophycin 55 in sequential and simultaneous combination
      treatment regimens in human tumor xenografts.
AB  - The antitumor activity of cryptophycin 52 (C52) and cryptophycin 55 (C55) in
      sequential and simultaneous combination treatment regimens in human tumor
      xenografts models was explored. The antitumor activity of C52 and C55 was
      compared alone and in sequential combination with gemcitabine or paclitaxel in
      four lung cancer models, H460 and Calu-6 NSCLC and SW2 and H82 small cell lung
      carcinoma. The combination of C52 followed by gemcitabine was additive in three
      tumors and greater-than-additive in the fourth. The combination of C55 followed
      by gemcitabine was additive in three tumors and less-than-additive in the fourth.
      The combination of C52 followed by paclitaxel was greater-than-additive in one
      tumor, additive in one tumor and less-than-additive in two tumors. The
      combination of C55 followed by paclitaxel was greater-than-additive in two tumors
      and less-than-additive in two tumors. The simultaneous combination of C52 or C55
      with fractionated radiation therapy was assessed in the H460 NSCLC tumor. Both
      cryptophycins produced a tumor response that was additive along with radiation
      therapy. The HCT116 colon carcinoma was used to compare the antitumor activity of
      simultaneous or sequential combination of 5-fluorouracil or irinotecan with C52.
      C52 produced greater-than-additive tumor response when administered either
      simultaneously with or sequentially with 5-fluorouracil or iriniotecan. Finally,
      when administered to animals bearing intraperitoneal OVCAR-3 ovarian carcinoma,
      C52, docetaxel and paclitaxel resulted in mean survival times of 123, 80 and 85
      days compared with 72 days in the untreated controls. In combination with
      carboplatin, C52, docetaxel and paclitaxel resulted in mean survival times of
      140, 105 and 135 days. Cryptophycins have the potential to be useful
      chemotherapeutic agents in a wide variety of clinical combinations regimens.

PMID- 10945161
TI  - Effects of green tea on growth, food utilization and lipid metabolism in mice.
AB  - To find whether green tea has anti-obesity effects in mice, female ICR mice were
      fed on diets containing 1, 2 and 4% green tea powder for 16 weeks and the body
      weight and food intake were weighed. After the administration of green tea, the
      ovaries, kidneys, adrenals, liver, spleen, brain, pituitary and intraperitoneal
      adipose tissues in the mice were weighed and lipid levels in the serum and in the
      liver and serum leptin levels were measured. It was found that body weight
      increase and intraperitoneal adipose tissues were remarkably suppressed by the
      administration of diets containing 2 and 4% green tea powder. Food intake was
      suppressed by feeding the 4% green tea diet. Concentrations of total cholesterol
      in the liver, triglycerides in serum and liver and nonestrified fatty acids in
      serum from mice which were administered green tea diet were lower than those in
      the controls. Leptin levels in serum showed a decrease with green tea treatments.
      These results indicated that lipid metabolism in mice was suppressed by the
      administration of green tea powder and thereby the fatty accumulation and body
      weight increase was suppressed.

PMID- 10945162
TI  - Cryptal lymphocytic colitis: a new entity in baboons.
AB  - A baboon died of chronic, intractable diarrhoea. At autopsy gross examination
      revealed oedema, and signs of chronic inflammation in the entire colon. At
      histology, marked lymphocytic infiltration within the colonic epithelium covering
      the crypts was found. The term cryptal lymphocytic colitis is proposed for this
      previously unreported disease in baboons.

PMID- 10945163
TI  - Colonic type adenocarcinoma of male urethra.
AB  - A case of rare primary adenocarcinoma of the bulbomembranous portion of the male
      urethra is presented. The histological and immunohistochemical characteristics of
      this tumor are identical to those of colon adenocarcinomas. The pathogenesis can
      be explained either by neoplastic degeneration of globet cells found in the
      urethral epithelium or by malignant degeneration of persistent glandular elements
      that are embryonal residues. The patient was successfully treated with
      transurethral prostatectomy and with a high dose of radiation therapy.

PMID- 10945164
TI  - Peritoneal leiomyoid mesothelioma mimiking a metastasis of papillary carcinoma.
AB  - The authors describe a rare case of peritoneal mesothelioma. Cytological,
      histological and immunohistochemical characterization of the tumor allowed the
      differential diagnosis from papillary carcinoma and suggested the diagnosis of
      leiomyoid mesothelioma.

PMID- 10945165
TI  - Glycohistochemical monitoring of chemically induced sarcomas at different stages
      of tumorigenesis.
AB  - Malignant soft tissue tumors still represent a source of uncertainty and
      controversy concerning histogenetic origin and histological behavior. Considering
      this, chemically induced sarcomas furnish an attractive model for the elucidation
      of cellular alterations during tumorigenesis. This approach allows us to closely
      follow cyto- and histological changes within coherent stages of tumor
      development. The specimen under scrutiny comprised 35 rat tissue samples from day
      10 up to day 200 after benzo[a]pyrene injection. Additionally, for comparison and
      validation two human malignant fibrous histiocytomas (MFH) were investigated. The
      essential biological significance of protein-carbohydrate interactions warranted
      the histochemical application of synthetic tools (neo-glycoproteins-NGP) and
      lectins in order to reveal phenotypical dynamics in this aspect throughout the
      process of tumor development. Namely, 6 plant lectins (carbohydrate-binding
      proteins with defined saccharide specificity), 7 custom-made synthetic NGP (as
      the corresponding ligands visualizing endogenous lectins) and additionally three
      antibodies were employed. Characteristic cell populations were histochemically
      demonstrated in four stages of tumor development: exudation (n = 5), mesenchymal
      proliferation (n = 7), atypical granulation tissue (n = 7) and sarcoma (n = 16).
      Changes of glycohistochemical binding patterns were in close phenotypic relation
      to cellular activity, differentiation, local distribution as well as malignant
      transformation and tumor progression. At present, the new glycobiological
      features of the malignant phenotype substantiate the assumption that not only
      glycosylation but also the receptor display is altered upon carcinogenesis. In
      conclusion, this chronological longitudinal study takes advantage of the
      combination of a coherent model of tumorigenesis with innovative histochemical
      tools whose ligands are supposed to act as mediators of cell-cell- and cell
      matrix interactions. It clearly demonstrates the suitability of the
      glycohistochemical method for comparative approaches. The systematic analysis of
      glycohistochemical determinants will improve our understanding of the early tumor
      biological processes with potential implications for therapeutic interventions.

PMID- 10945166
TI  - Cellular accumulation of uPA-PAI-1 [correction of UPA-PAI-1] and uPA-PAI-2
      [correction of UPA-PAI-2] complexes in early (pT1) breast cancer: a new link in
      the uPA-UPAr-PAI chain.
AB  - OBJECTIVE: To investigate the role of uPA in early (pT1) breast cancer. METHODS:
      Immunohistochemistry (streptavidin-biotin-peroxidase system), using the Chemicon
      AB776 polyclonal antibody, which reacts with uPA-PA-1 and uPA-PAI-2 complexes,
      was performed. In addition, CD44std, Ki67, c-erb-B2, p53, ER and PR expression
      were studied on the same tissue samples by the same method. The results obtained
      were correlated with nodal invasion, with each other and with classical
      pathologic features such as histologic and nuclear grade by means of the Spearman
      test for nonparametric variables. RESULTS: The immunohistochemical reaction with
      uPA-PAI-1 and uPA-PAI-2 complexes was cytoplasmic and localized inside the tumor
      cells, with no, or only minimal reaction in the stromal cells. uPA-positivity
      detected by this method correlated significantly with ER expression (p = 0.031),
      PR expression (p = 0.030), favorable nuclear grade (p = 0.0087) and marginally
      with a low proliferation rate (p = 0.088), which was the opposite of the results
      reported by most other groups when studying either free uPA or uPA bound to its
      membrane receptor (uPAr) in similar tumors. CONCLUSION: From our results we
      conclude that uPA-PAI-1 and uPA-PAI-2 complexes are formed inside the tumor cells
      for the purpose of inactivating free or uPAr-bound uPA, which explains why our
      findings were the reverse of those obtained when studying these latter forms. A
      model incorporating our data and the present knowledge on the uPA-uPAr-PAI chain
      is proposed.

PMID- 10945167
TI  - Selective gene expression in hepatic tumor with trans-arterial delivery of
      DNA/liposome/transferrin complex.
AB  - Since hepatocellular carcinoma (HCC) is frequently presented at an advanced
      stage, only a small portion of patients with HCC can be treated with local
      modalities. Gene therapy is, therefore, one of the more promising approaches for
      patients with advanced HCC. To develop a new strategy for targeting gene delivery
      to the hepatic tumor, the efficiency of the transarterial delivery of liposome
      DNA complex was evaluated in VX2 carcinoma implanted into the liver of rabbits. A
      mixture of pSV-beta galactosidase plasmid (40 micrograms), lipofectin (80
      microliters), and transferrin (852 micrograms), the optimal proportion of which
      determined in vitro, was infused via the hepatic artery of a rabbit with VX2
      hepatic tumors. The efficiency of trans-arterial gene delivery was compared to
      that of intra-tumoral injection. Rabbits (5 in each group) were sacrificed 48
      hours after gene delivery and hepatic tissues were examined using X-gal staining.
      beta-galactosidase staining was observed exclusively within the tumor following
      the trans-arterial gene transfer. In contrast, adjacent peritumoral cells in
      addition to hepatic tumor cells were transfected by the intra-tumoral injection
      of transgene. These data indicate that enhanced gene expression in hepatic tumors
      is possible using trans-arterial delivery of the liposome-DNA complex.

PMID- 10945168
TI  - Characterization of a liver metastatic variant of murine K1735M2 melanoma cells.
AB  - Intraportal vein injection of highly metastatic K1735M2L5 cells consistently
      resulted in liver metastases (increases in the number of tumor nodules in the
      liver), whereas inoculation of K1735M2 cells rarely did so. K1735M2L5 cells
      invaded the basement membrane Matrigel in greater numbers than did K1735M2 cells,
      suggesting that the metastatic potential of K1735M2L5 cells is partly related to
      enhanced invasive properties. The adhesion to Matrigel- and laminin-coated
      substrates was enhanced in K1735M2L5 cells. The up-regulated expression of VLA-4
      and VLA-6 on the surface of K1735M2L5 cells was detected by flow cytometry. The
      RT-PCR and gelatin zymography study revealed that the secretion of MMP-2 was
      higher in K1735M2L5 cells than in K1735M2 cells. These results indicate that the
      invasive ability of K1735M2L5 cells may also be attributed to enhanced
      gelatinolytic activity as well as adhesiveness. K1735M2L5 cells grew more rapidly
      than K1735M2 cells and showed fibroblastoid morphology with loose cell-cell
      contacts as compared with K1735M2 cells. Thus, experimental models using highly
      metastatic K1735M2L5 cells would be useful for analyzing the molecular mechanism
      of tumor metastasis and for evaluating the efficacy of treatments for metastases
      which may have already occurred at the time of the diagnosis.

PMID- 10945169
TI  - Photodynamic therapy based on combined use of 5-aminolevulinic acid with a
      pheophorbide-a derivative for murine tumors.
AB  - BACKGROUND: 5-Aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT)
      appears to be a promising cancer treatment modality. Here, we investigated
      whether enhancement of 5-ALA-PDT by combining another photosensitizer, a
      pheophorbide-a derivative (PH-1126), is an option. MATERIALS AND METHODS: PH-1126
      (2.5, 5 or 10 mg/kg.bw) and 5-ALA (168 mg/kg.bw) were injected i.p. into C3H/HeN
      mice bearing squamous cell carcinoma (SCC) or BALB/c nude mice bearing L5178Y
      lymphoma. Afterwards, these mice received laser irradiations (630 nm for 5-ALA
      and 650 nm for PH-1126) with a total dose of 88 J/cm2. The results showed that
      PDT with 5-ALA plus PH-1126 at a low dose (2.5 mg/kg.bw) were well tolerated by
      both animal models, with resultant synergistically enhanced inhibition of tumor
      growth and/or survival advantage for the treated animals. CONCLUSION: This study
      demonstrated the usefulness of the combination of a low dose PH-1126 with 5-ALA
      for PDT of experimental tumors in vivo.

PMID- 10945170
TI  - Intraperitoneally implanted artificial pancrease with transkaryotic beta-cells on
      microcarrier beads in a diffusion chamber improves hyperglycemia after 90%
      pancreatectomy in rats.
AB  - BACKGROUND: Considering the difficulties in pancreas transplantation, the
      development of an artificial pancreas would be of great value. We have
      established a transkaryotic artificial beta-cell line, CHO/I, produced by
      transfecting the human proinsulin gene into the Chinese hamster ovary (CHO) cell
      line. The present study was designed to assess the value of an artificial
      pancreas using a diffusion chamber containing CHO/I cells. MATERIALS AND METHODS:
      Wistar rats rendered diabetic by 90% pancreatectomy were treated by implanting a
      diffusion chamber containing CHO/I cells cultured on microcarrier beads. RESULTS:
      The diffusion chamber containing microcarrier beads produced 100-folds more CHO/I
      cells than the chamber alone, as calculated from the secreted IRI in vitro. When
      diffusion chambers containing CHO/I cells on microcarrier beads were implanted
      into the peritoneal cavity of the 90% pancreatectomized rats, the fasting serum
      IRI level increased and the fasting blood glucose decreased to the normal level
      for 12 weeks. An intraperitoneal glucose tolerance test demonstrated, however,
      that the diffusion-chamber-implanted rats did not respond to glucose loading.
      CONCLUSION: An artificial pancreas using a diffusion chamber containing human
      proinsulin gene transfected cells might be a promising model for future clinical
      application.

PMID- 10945171
TI  - Detection of tumor mutant APC DNA in plasma of patients with sporadic colorectal
      cancer.
AB  - The aim of this study was to detect mutant APC DNA of tumor origin in the plasma
      of patients with sporadic colorectal carcinomas. The polymerase chain reaction
      (PCR) and the single strand conformation polymorphism (SSCP) procedures were
      employed to detect DNA alterations using primers to amplify the mutation cluster
      region of the APC gene. APC mutations were observed in 7 out of 11 archival
      colonic tumor specimens examined. Matching mutations in free plasma DNA of tumor
      origin were detected in 3 of the 7 patients (42.8%). The results of this
      preliminary report indicated the presence of APC DNA in plasma harboring the
      identical abnormal molecular signature of tumor APC DNA. Detection methods of
      mutant APC DNA in blood may prove useful in the screening and monitoring of
      patients at risk of or with colorectal cancer.

PMID- 10945172
TI  - Studies on erythrocytic methemoglobin reductase systems in Plasmodium yoelii
      nigeriensis infected mice.
AB  - BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining
      the equilibrium between hemoglobin and methemoglobin in blood. Exposure of red
      blood cells to oxidative stress (pathological/physiological) causes an impairment
      in this equilibrium. OBJECTIVE: To study the status of methemoglobin and the
      related reductase system during Plasmoidum yoelii nigeriensis (P. y. nigeriensis)
      infection in mice. METHOD: Mice were divided into two groups viz., normal mice
      and P. y. nigeriensis infected mice. Malaria infection was induced by
      intraperitoneal inoculation of 10(6) infected erythrocytes. RESULTS: The present
      investigation revealed significant decrease in the activity of methemoglobin
      reductase, with concomitant rise in methemoglobin content during P. y.
      nigeriensis infection in mice erythrocytes. This was accompanied with a
      significant increase in reduced glutathione and ascorbic acid levels. Also the
      activities of the associated enzymes viz., lactate dehydrogenase, glucose-6
      Phosphate dehydrogenase and glutathione reductase were found to increase with
      progressive rise in parasitemia. CONCLUSION: P. y. nigeriensis infection in mice
      results in impairment of methemoglobin reductase in the host.

PMID- 10945173
TI  - Vaccination with soluble low-molecular weight tumor-associated proteins
      suppresses chemically-induced mammary tumorigenesis in rats.
AB  - This study attempted to elucidate whether the soluble tumour-associated proteins
      (TAA) of 66 kDa and 51 kDa molecular weight could suppress chemically induced
      mammary tumorigenesis. An intragastric dose of dimethylbenzanthracene (DMBA) was
      administered to rats and some were simultaneously immunised with the TAA. A
      single dose of DMBA resulted in 38% of the rats developing mammary tumours.
      However, simultaneous vaccination with the TAA preparation was significantly
      tumour-suppressive: mortality declined from 50% to 0% (p < 0.05); survival was
      extended from 9.4 weeks to 13.0 (p < 0.05), and 83% of the animals remained
      tumour free, compared to 13% of the control animals (p < 0.05). In 33% of the
      immunised animals the malignant tumours regressed completely. Such vaccination
      was also effective, although to a lesser extent, when the carcinogen dose was
      doubled. Then, 33% of the immunised and 22% of the control animals remained
      tumour-free, the latent period of malignant transformation was extended from 10.0
      to 11.7 weeks, the initial tumour-free period lasted 9.3 weeks instead of 8.3
      weeks and 10% survived compared to 50% of the controls. Vaccination with the
      soluble low molecular-weight TAA had distinct tumour-suppressive effects on
      mammary gland tumorigenesis.

PMID- 10945174
TI  - Minimal intervention dentistry--a review. FDI Commission Project 1-97.
AB  - The concept of minimal intervention dentistry has evolved as a consequence of our
      increased understanding of the caries process and the development of adhesive
      restorative materials. It is now recognised that demineralised but noncavitated
      enamel and dentine can be 'healed', and that the surgical approach to the
      treatment of a caries lesion along with 'extension for prevention' as proposed by
      G V Black is no longer tenable. This paper gives an overview of the concepts of
      minimal intervention dentistry, describes suggested techniques for a minimally
      invasive operative approach, and reviews clinical studies which have been carried
      out in this area.

PMID- 10945175
TI  - Oral health in Hlabisa, KwaZulu/Natal--a rural school and community based survey.
AB  - AIMS: To investigate rates of dental caries and periodontal disease, available
      dental services and resources and perceived needs in a rural South African
      community. DESIGN: A cross-sectional field study including situational analysis
      and focus group discussions. SETTING: KwaZulu/Natal, South Africa. PARTICIPANTS:
      A total of 520 children, adolescents and adults. METHODS: WHO caries scores and
      periodontal CPI score were determined through clinical examinations in five age
      groups, 5-6 years, 12 y, 15 y, 35-54 y, 55 y+. Focus groups included ten 15-year
      old children and ten adults. RESULTS: Caries prevalences and (mean scores) were 5
      6 y 64% (dmft 3.0), 12 y 24% (DMFT 0.4), 15 y 27% (DMFT 0.8), 35-54 69% (DFT 2.6)
      and 55 y+ 80% (DFT 2.7). Most caries was untreated and where present, treatment
      had been extraction. Dental caries rates were low and except for 5-6 y were
      within WHO targets for the year 2000. Periodontal disease prevalence was high but
      would respond to improved oral hygiene. Knowledge of oral health was rudimentary.
      CONCLUSIONS: A district-wide oral health promotion programme is required preceded
      by research to define effective health education messages. Access to simple but
      effective preventive and curative services would seem reasonable. In view of the
      lack of resources ART is suggested as caries treatment.

PMID- 10945176
TI  - The effect of different commercial dentifrices on enamel lesion progression: an
      in vitro pH-cycling study.
AB  - AIMS/OBJECTIVES: To evaluate and compare the de/remineralization effects of
      dentifrices manufactured locally in some developing countries. DESIGN:
      Utilisation of the in vitro single-section and the pH-cycling model. SETTING:
      Laboratory. TEST MATERIALS: Dentifrices: Maxam DFP, Maxam Tartar Control, First,
      Tianqi Medicated from China; Vicco Vajradenti from India; Colgate MFP2, Crest
      Tartar Control from USA; and one non-fluoride dentifrice as control. METHODS:
      Sound molars were painted, leaving a 1 mm wide 'window' on the buccal and/or
      lingual surface and placed in a demineralisation solution for 96 h to produce
      artificial caries lesion approximately 80-100 mm deep. The teeth were then
      longitudinally sectioned (approximately 100 mm thick), and randomly divided into
      8 groups (22 sections/group). The pH cycling model was utilised for 10 days.
      OUTCOME MEASURES: Polarised light microscopy and microradiography were used to
      evaluate the lesion progression before and after treatment. RESULTS: The control
      group showed an increase in lesion depth of 70 per cent and was statistically
      different from some test groups which ranged from -2 per cent to 68 per cent (P <
      0.01, t-test). Statistically significant differences were also observed among
      some of the fluoride containing groups. CONCLUSIONS: This study suggests that,
      when compared to 'multinational dentifrices', Chinese and Indian dentifrices
      manufactured locally failed to show 'healing' efficacy even though they claimed
      to contain varying levels of fluoride.

PMID- 10945177
TI  - The role of the dental hygienist in the public health sector; an Australian
      perspective.
AB  - A review of the literature on dental hygienists and their utilisation in the
      dental workforce is presented. Dental hygienists are employed as part of a dental
      team in the prevention and management of the two most common and costly oral
      diseases; dental caries and periodontal disease. The potential scope for dental
      hygienists in the public health sector in Australia is examined in the light of
      broader issues relating to changing disease patterns, service delivery and the
      treatment of patients with special needs. Prevention and treatment of oral
      disease by the dental hygienist in schools, institutions, nursing homes,
      hospitals and residential facilities is discussed, with emphasis on such issues
      as legislation, productivity and quality assurance. Implications for the future
      training of dental hygienists are presented and recommendations made for
      increasing their utilisation in the public sector.

PMID- 10945178
TI  - Occupational health problems of dentists in southern Thailand.
AB  - AIMS: To investigate the prevalence and nature of some occupationally related
      health problems in dentists in southern Thailand. DESIGN: A cross-sectional study
      using a self-report questionnaire distributed to all 220 dentists working in 14
      provinces in southern Thailand in 1997. PARTICIPANTS: One hundred and seventy
      eight dentists aged between 22 to 54 years responded. RESULTS: The most common
      occupational health problems were musculoskeletal pain (78 per cent) and
      percutaneous injury (50 per cent). Associated factors were analysed using
      multivariate analysis. About 22 per cent of these dentists had a history of
      contact dermatitis mostly caused by allergy to latex gloves, 15 per cent had eye
      problems, and 3 per cent had hearing problems. CONCLUSIONS: Continuing education
      in the avoidance of percutaneous injuries would be beneficial, as exposure to
      potential infectious agents is of concern. Further studies are needed to identify
      causes of musculoskeletal pain and to identify appropriate interventions to
      reduce its prevalence, as would similar measures to reduce exposure to agents
      which may be producing contact dermatitis.

PMID- 10945179
TI  - Dental caries experience in Mexican schoolchildren from rural and urban
      communities.
AB  - OBJECTIVE: To compare dental caries experience in Mexican rural and urban
      settings. DESIGN: Cross-sectional samples of schoolchildren. SETTING: A school in
      Mexico City and a rural school in a remote area of the Oaxaca State in Southern
      Mexico. SAMPLE AND METHODS: A total of 347, 9- to 10-year-old schoolchildren
      (rural area, 131 children; urban, 216) was examined by two standardised dentists
      using the WHO 1987 criteria. OUTCOME MEASURES: Data were analysed in terms of
      central tendency measures and 95 per cent confidence intervals. RESULTS: Caries
      prevalence was 91.6 per cent in the urban area, and 54.4 per cent in the rural
      area (P < 0.05). DMFT in 10-year olds was 1.93 (sd 1.72) and 0.40 (sd 0.76) in
      urban and rural areas respectively (95 per cent CI 1.16-1.89). The entire
      DMFT/dmft indices in the rural group were made up of the decayed component.
      CONCLUSIONS: There is a large difference in the prevalence and distribution of
      dental caries between rural and urban Mexican children. Dental treatment
      background also differs markedly. Findings highlight the need to establish
      distinct preventative and rehabilitative treatment strategies tailored to meet
      the specific needs of different population groups.

PMID- 10945180
TI  - Cross-cultural differences of self-reported oral health behaviour in Japanese and
      Finnish dental students.
AB  - OBJECTIVE: To determine whether any differences existed in dental health
      behaviour between Japanese and Finnish dental students. SETTING: Hiroshima
      University School of Dentistry and the University of Helsinki. DESIGN: Comparison
      of cross-cultural differences of self-reported oral health behaviour. SUBJECTS:
      Dental students, 337 in Japan and 113 in Finland. METHOD: Subjects were surveyed
      using the Japanese and Finnish versions of a 20-item questionnaire entitled
      Hiroshima University--Dental Behavioural Inventory (HU-DBI). RESULTS: Only 2 per
      cent of Finnish students reported that they put off going to the dentist until
      they had toothache, compared to 56 per cent of Japanese students. Similarly,
      significantly more Japanese students thought that their teeth were getting worse
      despite their daily brushing, compared to their Finnish peers. The mean HU-DBI
      score of Year 1 Finnish students was higher than that of their Japanese peers,
      which suggested a higher level of dental health awareness in Finnish students
      upon entry into dental school. The mean scores of the Japanese students were
      lower than those of their Finnish peers until Year 3. The mean scores of Year 5
      and Year 6 Japanese students were higher than that of Year 1 students, indicating
      raised self-care levels influenced by the course in preventive dentistry. The
      gender difference of the HU-DBI score was not a major feature in either country.
      CONCLUSIONS: Self-reported oral health behaviours seemed to be very different
      between the two countries, which reflected different culture and/or health
      education systems of the students.

PMID- 10945181
TI  - Demineralisation and remineralisation of dentine caries, and the role of glass
      ionomer cements.
AB  - In accordance with the principles of modern operative dentistry, to conserve
      tooth structure and to use therapeutic restorative materials, an understanding of
      the carious process in dentine and the biological properties of glass-ionomer
      cements (GICs) are necessary. Delineation of the outer necrotic from the inner
      vital and remineralisable carious dentine allows for the preservation of tooth
      structure. This delineation is not possible when relying on visual and tactile
      perceptions, but requires the use of a caries detecting dye. GICs are ideal
      dentine substitutes because of their anticariogenic properties, stable long-term
      ionic bonding, and ability to assist the process of remineralization. The range
      of usage of these restorative materials continues to expand with the development
      of improved products.

PMID- 10945182
TI  - Fibronectin levels in stimulated whole-saliva and their relationship with
      cariogenic oral bacteria.
AB  - AIM: Fibronectin is a multifunctional glycoprotein that plays a fundamental role
      in mechanism of cellular union and in bacterial adhesion in the oral cavity. The
      aim of this study was to test the clinical relationship between fibronectin
      concentration in stimulated whole-saliva and the number of Mutans streptococci
      bacteria. PARTICIPANTS: The sample consisted of 167 children aged 12 years.
      METHODS: Saliva samples were collected from the subjects. Bacterial
      quantification was carried out using a semiquantitative method (Dentocult SM,
      Vivadent). Fibronectin was measured by the ELISA method with modifications.
      RESULTS: An inverse clinical relation was found between the levels of soluble
      fibronectin and the number of SM colony forming units. CONCLUSIONS: Bacterial
      counts sufficiently high to destroy the protein films increase bacterial binding
      to dental surfaces, thereby contributing to the regulation of bacterial plaque
      composition and its pathogenic potential. This capacity of glycoproteins to
      reduce the adhesion of microorganisms to the oral tissues and favour macrophage
      action supports the hypothesis that such proteins contribute to the first line of
      immune defence together with secretory antibodies.

PMID- 10945183
TI  - The work patterns of male and female dental practitioners in the United Kingdom.
AB  - AIM: The aim of the study was to determine differences between male and female
      dental practitioners in the type of dentistry they practice, and their working
      practice, and to compare these data to previously published studies of the
      working practices of female dentists in the United Kingdom. DESIGN: A postal
      questionnaire survey. PARTICIPANTS: A 1 in 10 sample of individuals taken from
      the UK Dentists Register. RESULTS: The data revealed that women dentists are more
      likely than male dentists to work in the Community Dental Service. Within general
      dental practice women are more likely to work part-time, to carry out National
      Health Service treatment and to specialize in orthodontics or paediatric
      dentistry. More women than men take career breaks, and the reasons for taking
      career breaks differ between male and females. Women take longer career breaks on
      average. However, differences between male and female practitioners in the total
      duration of their career breaks are largely accounted for by child rearing.
      Finally, male dental practitioners are more likely than female dental
      practitioners to report reading professional journals. The findings are analysed
      in the light of previous surveys of the working practices of female dental
      practitioners both within the United Kingdom and internationally. CONCLUSION: The
      main finding reported here is that there are no differences between men and women
      in the number and length of career breaks taken, if childcare is excluded.

PMID- 10945184
TI  - Utilisation of dental services in Tanzania before and after the introduction of
      cost-sharing.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of cost
      sharing, introduced in July 1994, on the utilisation of dental services in
      Tanzania. METHODS: The study compared dental attendance, demand for dental
      services and treatment pattern of patients in 17 out of 20 regions of mainland
      Tanzania in 1993 and 1995, a year before and after the introduction of user fees.
      OUTCOMES MEASURES: Dental attendance and demand for treatment. RESULTS: Results
      revealed a 33.2 per cent overall reduction in dental attendance but no effect on
      either the demand for treatment or treatment pattern. The exceptions were
      increases in referral cases by 14.5 times and prosthetic work by 3.9 times, and a
      reduction in surgical cases by 18.8 per cent. CONCLUSIONS: In order to improve
      attendance and decrease referrals it is necessary to enforce the first line of
      oral primary health care to meet the simple treatment demands. Furthermore, the
      revenue generated by cost-sharing should be used to improve services.

PMID- 10945185
TI  - Grievances in cases using antibiotics due to orodental problems and assessment of
      the need for antibiotics.
AB  - OBJECTIVE: To assess the complaints of patients who were prescribed antibiotics
      following orodental problems and the need for antibiotics prescribed for this
      purpose. SETTING: Examinations were carried out in the Department of Oral
      Diagnosis and Radiology, Ege University, Turkey. PARTICIPANTS: A total of 203
      patients (129 females and 74 males) between 8-70 years of age (mean age 37.7 +/-
      13.9). INTERVENTION: Examination and report. MAIN OUTCOME MEASURES: Frequency of
      unnecessary antibiotic use. RESULTS: Antibiotic therapy was not necessary for 151
      (74.4 per cent) cases. Antibiotics were unnecessarily prescribed in 45 cases of
      acute irreversible pulpitis, 10 chronic apical abscess, 6 acute apical
      paradontitis, 7 gingivitis, 10 periodontitis, 4 epulis, 2 TMJ (temporomandibular
      junction) dysfunction, 2 sharp ridge of alveolar bone, 1 burning mouth syndrome
      and 1 recurrent aphthous stomatitis. In 108 (53.2 per cent) of the cases, the
      prescribed antibiotics were found to be penicillins, 102 of which were broad
      spectrum. It was also determined that only 6 (7.7 per cent) of the 78 cases
      diagnosed as acute apical abscess were given drainage as local therapy.
      CONCLUSIONS: Principles for treating dental infections suggest that an antibiotic
      should only be used to supplement and not substitute for conventional surgical
      methods. Therefore, in cases with acute apical abscess, mechanical treatment
      (drainage) should be the first step. Inappropriate antibiotic use is quite
      widespread in dentistry. Dentists should avoid inappropriate use of antibiotics.
      To prevent inappropriate administration, necessary precautions need to be taken
      against dispensing antibiotics without prescription.

PMID- 10945186
TI  - In vitro colonisation of acrylic resin denture base materials by Streptococcus
      oralis and Actinomyces viscosus.
AB  - AIM: The aim of the study was to compare the attachment of two typical strains of
      oral bacteria to four denture base materials. DESIGN: In vitro study. METHOD:
      Discs of acrylic resin denture base materials (Paladon 65, polished and
      unpolished; Palapress; Microbase, polished and unpolished, and Triad VLC) were
      placed into Petri dishes with Schaedler's medium, inoculated with Streptococcus
      oralis 34 or Actinomyces viscosus T14V. MAIN OUTCOME MEASURES: After 24 h or 48 h
      the numbers of adhering bacteria were measured. RESULTS: The bacteria adhered to
      all discs in similar numbers: 3-9 x 10(6)/ml (viable cell count) and 9-22 x
      10(8)/ml (total cell count) for T14V, and 2-6 x 10(6)/ml (viable cell count) and
      1.5-3 x 10(8)/ml (total cell count) for 34. CONCLUSIONS: Polishing had little
      effect on adherence. Denture base materials are not resistant against adherence
      and possible surface damage by oral bacteria. Therefore, thorough oral hygiene is
      important for denture wearers.

PMID- 10945187
TI  - Causes and prevalence of traumatic injuries to the permanent incisors of school
      children aged 12 years in Jaragua do Sul, Brazil.
AB  - AIM: To assess the causes and the prevalence of traumatic injuries to the
      permanent incisors of 12-year-old schoolchildren in Jaragua do Sul, Brazil.
      DESIGN: Cross-sectional survey. SETTING: Public and private primary schools.
      PARTICIPANTS: 476 children of both sexes, selected by multistage sampling
      technique. METHODS: Clinical examination of upper and lower permanent incisors.
      MAIN OUTCOME MEASURES: Incisal overjet, lip coverage, traumatised anterior teeth,
      cause of trauma. Parents' levels of education and employment status and family
      income. RESULTS: Boys experienced double the percentage of injuries compared to
      girls. Children with incisal overjet greater than 5 mm (P = 0.077) and inadequate
      lip coverage (P = 0.667) were not more likely to have experienced dental
      injuries. The main causes of injuries to the permanent incisors were falls (26
      per cent), traffic accidents (20.5 per cent), sports (19.2 per cent), violence
      (16.4 per cent) and collisions with people or inanimate objects (6.8 per cent).
      Socio-economic measures had no significant effect on prevalence of trauma.
      CONCLUSIONS: Policy makers must take the causes of trauma into account when
      developing a strategy for the prevention of dental injuries. The role of violence
      in causing traumatic dental injuries has been underestimated.

PMID- 10945188
TI  - The effect of glass fibre-reinforcement on the transverse strength, deflection
      and modulus of elasticity of repaired acrylic resins.
AB  - AIM: To test the effect of reinforcement qualities of glass fibre in the repair
      of acrylic fractures. METHODS: Four types of heat-curing acrylic resin test
      specimens were fabricated. The bottom and sides of the specimens were placed in
      stone to form a repair template. Lines were drawn 3.5 mm on each side of the
      centring mark. The 45 degree-bevel joint margins were cut at these lines to
      simulate fracture and the centre section was discarded. A 1 mm gap was created
      between the margins before repair with autopolymerising acrylic resin with and
      without glass fibre. OUTCOME MEASURES: A three-point loading test was used to
      measure transverse strength, deflection and the modulus of elasticity of repaired
      acrylic resin joints. RESULTS: The transverse strength of acrylic resins was
      increased with fibres. CONCLUSION: Glass fibre-reinforcement significantly
      increased resistance to deflection and increased the modulus of elasticity.

PMID- 10945189
TI  - Tobacco and oral health: attitudes and opinions of European dentists; a report of
      the EU working group on tobacco and oral health.
AB  - AIM: To discover whether dentists are prepared to advise their patients to stop
      smoking. DESIGN: Postal questionnaire. SETTING: Member countries of the European
      Union. PARTICIPANTS: Dentists in 12 EU countries. MAIN OUTCOME MEASURES:
      Dentists' knowledge of links between tobacco-use, general health and periodontal
      health. Knowledge of, and preparedness to offer, tobacco-cessation activities for
      patients. Personal and practice smoking policies. RESULTS: EU-dentists are aware
      of the harmful effects of tobacco use in general and on oral tissues in
      particular. Over two-thirds of EU-dentists feel that offering information about
      tobacco cessation is the dentist's duty, while slightly less actually do so. Lack
      of time and reimbursement mechanisms are the most often mentioned barriers for co
      operation with a campaign. Less than 10 per cent of EU-dentists smoke every day
      while three-quarters of practices are totally smoke free. CONCLUSIONS: EU
      dentists want to be informed and supported on the issue by leaflets, brochures,
      continuing education and patient education materials. More attention should be
      paid to the relation of smoking and implant failure.

PMID- 10945190
TI  - Bacterial aerosols in the dental clinic: effect of time, position and type of
      treatment.
AB  - OBJECTIVES: The objectives of this study were to investigate changes in the
      concentration of total bacterial aerosols before, during, and after the working
      period at different positions within the same multichair dental clinics. Also to
      investigate the contribution to total bacterial aerosols, if any, of the aerosols
      generated from different types of dental procedures, as well as the environment.
      METHODS: Air sampling using a Slit-to-Agar air sampler at three positions in a
      multichair dental clinic, performed three times per day over a three week period
      before work, during work and after work. The second part of the study, in another
      multichair dental clinic, was performed before working and during three types of
      dental procedures. RESULTS: The concentration of total bacterial aerosols and
      Bacillus sp. in air which circulated in the dental clinic was lower at the end of
      the day than at the beginning. There was no significant change in the
      concentration of total bacterial aerosols in different positions in the dental
      clinic or after the three types of dental treatments. The concentration of
      Bacillus sp. in air not mainly generated during dental procedures and which may
      come from an environmental source, was reduced. CONCLUSIONS: This study suggests
      that the proportions of different types of bacteria in air may change before,
      during and after dental treatment. Preventive measures may need to be instituted
      to reduce build up of bacterial aerosols in the dental clinic during non-working
      periods.

PMID- 10945191
TI  - Meningioma manifested as temporomandibular joint disorder: a case report.
AB  - Pain in the temporomandibular joint (TMJ) and the surrounding region constitutes
      a symptom of TMJ disorders. Various dental causes usually stimulate the
      trigeminal nerve, developing facial pain which triggers trigeminal neuralgia.
      However, trigeminal neuralgia may also arise from irritation of the endocranial
      root of the nerve, due to occult damage which has not yet manifested other
      symptoms, for example a meningioma. In this manner, the actual cause of pain in
      the ipsilateral half of the face may be interpreted incorrectly and may possibly
      be attributed to a TMJ dysfunction syndrome. This results in long-term
      frustration and burdening of the patient. The case of a 47-year-old woman is
      presented who complained of symptoms of a painful TMJ disorder. She was initially
      treated with the appropriate dental procedures and, upon continuation of the
      pain, was examined with CT scanning, which proved to be negative despite the
      existence of a cerebral lesion. Further investigation with MRI, however, revealed
      a meningioma of 5 mm size, in the region of the cerebellopontine angle.

PMID- 10945192
TI  - A guest editorial: neurocysticercosis.

PMID- 10945193
TI  - Use of misoprostol in obstetrics and gynecology.
AB  - Misoprostol is prostaglandin E1 analogous and marketed for prevention and
      treatment of peptic ulcer disease. However, it has been used widely in obstetrics
      and gynecology practice because of its effectiveness, low cost, stability in
      light and hot climate conditions, and ease of administration compared with its
      licensed counterparts--dinoprostone and gemeprost. A large number of studies have
      shown that misoprostol is effective in first and second trimester abortion, late
      pregnancy labor induction, and third stage of labor management (misoprostol has
      not been approved by the U.S. Food and Drug Administration for these
      indications). Because misoprostol is not registered for such use, it has not
      undergone the extensive testing for appropriate dosage and safety required for
      registration. Serious complications such as teratogenesis after failed abortions
      and uterine rupture during second trimester abortions and third trimester labor
      induction have been reported as the result of increasingly wide use of
      misoprostol in obstetric and gynecology practice. There is an urgent need to
      evaluate all the available data and organize a large randomized trial to
      determine the safety of its use in obstetric and gynecology practice. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader will be able to identify the various
      uses of misoprostol, to describe the potential complications of misoprostol use
      and its teratogenic effects, to compare the various routes of administration, and
      to define the appropriate dose.

PMID- 10945194
TI  - Role of angiopoietins in reproductive tract angiogenesis.
AB  - Components of the female reproductive system undergo a number of programmed
      angiogenic processes coupled with cyclic evolution and decline of ovarian,
      endometrial, and placental structures. The development of a new vascular network
      requires a remarkable degree of coordination between different cell types
      undergoing complex changes. This implies that the expression of the inciting
      angiogenic factors are hormone dependent. Recently, a second family of vascular
      endothelial growth factors was identified, the angiopoietins. Angiopoietins are
      vascular endothelial cell-specific growth factors that play important roles
      principally during the later stages of angiogenesis, after the induction of new
      capillaries by vascular endothelial growth factor (VEGF). There are four known
      angiopoietins, and their specificity for the vascular endothelium results from
      the restricted expression pattern of their tyrosine kinase receptor, Tie2. In
      this review, we discuss the molecular characterization and mechanism of action of
      angiopoietin-1 and angiopoietin-2 in reproductive tract angiogenesis. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES:
      After completion of this article, the reader will be able to describe the
      angiogenic process and specifically explain the role of angiopoietics in
      reproductive tract angiogenesis and compare the differences between the various
      proteins that are involved in angiogenesis.

PMID- 10945195
TI  - Margin status and excision of cervical intraepithelial neoplasia: a review.
AB  - Excisional biopsy of the cervix for diagnosis and treatment of cervical neoplasia
      is common. Management of patients with involved margins of resection is
      unresolved. Data concerning use of thermal techniques show that this technique
      yields equivalent results in most cases. Important exceptions are microinvasive
      squamous disease and adenocarcinoma. Conservative management of involved squamous
      margins is possible. Techniques for follow-up include cytology, colposcopy, and
      endocervical curettage. Adenocarcinoma in situ (AIS) should be treated with cold
      knife conization. The standard of care for AIS is hysterectomy except in certain
      specific indications. Data concerning technique, follow-up, use of endocervical
      curettage, and the need for reexcision will be presented. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader will be able to compare the efficacy of
      the various excisional procedures in the treatment of cervical dysplasia, list
      the indications for additional surgery after positive margins on cervical
      excisions, and describe the proper management of a patient with adenocarcinoma in
      situ.

PMID- 10945196
TI  - Assistance programs available for medications commonly used in transplant
      patients.
AB  - Pharmaceutical manufacturers have programs available to supply medications to
      indigent patients at little or no cost. Enrolling needy patients into these
      programs should increase patient compliance to medications, minimize patient and
      institution financial burdens, and decrease adverse events associated with
      medication noncompliance. However, access to assistance programs by patients in
      need is limited if physicians and other health care providers are unaware of the
      existence of such programs or not informed of each program's enrollment process.
      The literature is void of a manuscript describing assistance programs available
      for commonly prescribed medications used in transplant patients. This article
      offers a concise summary of medication assistance programs available through the
      pharmaceutical industry to assist in the procurement of medications that are
      commonly prescribed for the transplant population, including immunosuppressants,
      antibacterials, gastrointestinal, cardiovascular, and hypoglycemic agents. This
      article should be used by health care professionals as a guide to the
      availability and requirements of medication assistance programs.

PMID- 10945197
TI  - Improved outcome of pulmonary aspergillosis in heart transplant recipients with
      early diagnosis and itraconazole treatment.
AB  - Pulmonary aspergillosis is a severe complication in heart transplant recipients.
      The drug of choice for this infection is amphotericin B, but its use is limited
      because of its side effects. We observed six cases of pulmonary aspergillosis in
      a group of 200 patients who had received heart transplants from January 1988 to
      January 1999. Predisposing factors such as previous rejection, neutropenia and/or
      cytomegalovirus reactivation were present in all patients. The clinical
      presentation was characterized by fever and a non-productive cough. X-rays showed
      monolateral or diffuse infiltrate with or without nodular lesions. The median
      interval between symptoms and diagnosis was 5 d (range 4-7). Diagnosis was made
      by culturing trans-tracheal aspirate samples. Aspergillus fumigatus was isolated
      in 3 patients and A. niger in the other 3. All patients were treated with
      itraconazole at 200-400 mg/day for 20-60 d and all recovered. One patient treated
      with the lowest dosage for the shortest term had a recurrence after 1 month and
      needed a second 30-day course of itraconazole at a higher dosage. No significant
      side effects were registered. Itraconazole is effective in the therapy of
      pulmonary aspergillosis, particularly when an early diagnosis is made.

PMID- 10945198
TI  - Simultaneous pancreas-kidney transplantation: portal versus systemic venous
      drainage of the pancreas allografts.
AB  - Simultaneous pancreas-kidney (SPK) transplantation is considered a valid
      therapeutic option for patient with type I diabetes mellitus and end-stage
      diabetic nephropathy. This study was performed to determine whether the technique
      of pancreas venous drainage affects patient survival as well as graft survival
      and function. From October 1996 to April 1999 34 uremic patients with type I
      diabetes mellitus were randomly assigned to two groups: the first group (SV group
      = 17) received SPK transplantation with systemic venous drainage, and the second
      group (PV group = 17) received pancreas allograft with portal drainage. A Roux-en
      Y loop was performed in all the patients. Patient follow-up included clinical
      course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the
      SV group and 94.1% in the PV group while graft survival rate was 76.4% in both
      groups. Several surgical complications were attributed to the enteric drainage
      without any graft failure in both groups. One venous thrombosis occurred in each
      group. No significant differences have been evidenced in kidney and pancreas
      function. The preliminary results of this randomized trial did not evidence any
      significant differences between portal and systemic venous drainage of pancreas
      allograft.

PMID- 10945199
TI  - Knowledge and opinions about organ donation among urban high school students:
      pilot test of a health education program.
AB  - BACKGROUND: Increasing the diversity of the organ donor pool might improve the
      opportunities for people of color on organ transplant waiting lists to receive
      donated organs. We report on the results of a pilot classroom health education
      program to improve knowledge about organ donation and transplantation among a
      diverse student body at an urban high school. METHODS: The effectiveness of the
      educational program was evaluated with baseline and follow-up questionnaires
      which examined: 1) whether the program increased knowledge about organ donation;
      2) whether the students' opinions about organ donation changed; and 3) whether
      the program was related to any changes in opinion. RESULTS: On the follow-up
      questionnaire, correct answers on 15 factual questions increased by 18% for the
      treatment group, compared to 5% for the control group (p = 0.00). Regarding
      opinions, at baseline 92% of white students had positive opinions about donation,
      compared to 48% of the students of color (p = 0.00). In the follow-up survey, the
      increase in positive opinions among the students of color was significantly
      greater than among white students (p = 0.04). In this pilot study, however,
      changes in opinions occurred with equal frequency among students in the treatment
      and control groups. In regression analysis, both knowledge of the subject and
      discussing donation with one's family were significantly associated with positive
      opinions about donation. CONCLUSIONS: Overall, this pilot study provided
      encouraging evidence that the classroom health education program affected
      knowledge about organ donation, and that opinions about organ donation are
      responsive to increases in knowledge.

PMID- 10945200
TI  - Cost-benefit analysis of a clinical pharmacist-managed medication assistance
      program in a renal transplant clinic.
AB  - Medicare pays for 80% of the cost of immunosuppressant agents needed within the
      first 3 years of solid organ transplantation; however, many patients cannot
      afford the remaining 20%. Furthermore, many patients who are beyond 3 years post
      transplantation and have prescription coverage cannot afford the co-payment for
      these medications. Other patients may not be able to afford their medications due
      to limited or no insurance coverage. The Medical College of Georgia (MCG) has
      been giving immunosuppressant medications to renal transplant patients if they
      cannot afford to pay for them. To assist MCG with drug cost for medications and
      maintain quality care for renal transplant patients, a clinical pharmacist
      managed medication assistance program was implemented to procure
      immunosuppressants from pharmaceutical manufacturers. METHODS: All patients
      enrolled in medication assistance programs from 1 January 1998 through 31
      December 1998 were included in this analysis. Medication acquisition costs with
      and without Medicare reimbursement and the cost of implementing the clinical
      pharmacist-managed medication assistance program were used to determine the value
      of implementing this service. RESULTS: Sixty-one patients were enrolled in
      manufacturers' assistance programs and a net cost avoidance of $124,793 was
      realized for the year of the program (benefit-to-cost ratio of 7.5:1). Assuming
      that the hospital collected the maximum amount allowed for patients receiving
      Medicare benefits, a cost avoidance of $69,233 was calculated (benefit-to-cost
      ratio of 4.16:1). CONCLUSIONS: A clinical pharmacist-managed medication
      assistance program in a renal transplant clinic produced substantial cost savings
      over this 1-year study period. For each dollar spent in pharmacist's time, a
      minimum of $4 was returned to the institution.

PMID- 10945201
TI  - Usefulness of quantitative real-time polymerase chain reaction in following up
      patients with Epstein-Barr virus infection after liver transplantation.
AB  - BACKGROUND: Post-transplant lymphoproliferative disease (PTLD), which is mainly
      induced by Epstein-Barr virus (EBV) infection, is a cause of significant
      morbidity and mortality for patients undergoing liver transplantation, especially
      when it is detected at such an advanced stage as monoclonal malignant lymphoma.
      METHODS: In this series, 6 of 22 liver transplant patients suffered from EBV
      infection. We tested quantitative DNA (Qt-DNA) by real-time polymerase chain
      reaction (PCR), qualitative DNA in plasma (Q1-pDNA) by PCR, and EBV-encoded mRNA
      1 (EBER 1) by in situ hybridization to clarify which of them is a better marker
      for the early diagnosis and prediction of EBV-associated disorders. RESULTS: Four
      had signs or symptoms of PTLD, but 2 did not develop individualized lymphoid
      lesions. In all patients, both Qt-DNA and EBER 1 exceeded the cut-off level of
      10(2.5) copies/microg DNA and 0.002%, respectively, at the time of diagnosis. In
      2 patients, when Qt-DNA had a poor decline, EBER 1, even if it seemed to decrease
      after antiviral therapy, increased again after a few months and the clinical
      symptoms recurred. In 2 patients, Qt-DNA and EBER 1 increased again after a few
      months of antiviral therapy, and Q1-pDNA remained positive, whereas, in 3
      patients, no reaction of EBV could be detected once Q1-pDNA became negative, even
      after the cessation of therapy. CONCLUSIONS: These results suggest that real-time
      PCR for Qt-DNA was more sensitive to the real-time activity of EBV and that Q1
      pDNA could indicate when to stop antiviral therapy.

PMID- 10945202
TI  - Outcome for arterio-venous fistula at the elbow for haemodialysis.
AB  - BACKGROUND: Few studies have examined the outcome of arterio-venous fistulas
      (AVF) at the elbow for haemodialysis. METHODS: All AVFs at the elbow created
      between 1994 and 1998 were identified retrospectively from case notes and the
      computerised database. Patients were followed until fistula failure, death, or
      for a minimum of 6 months until June 1999. Life table analysis and Kaplan-Meier
      actuarial curves with the log rank test were used to assess the influence of age,
      sex, diabetes, hypertension, heart disease, cerebrovascular disease, use of
      erythropoietin, aspirin or warfarin, previous insertion of subclavian vein
      catheter and the levels of haemoglobin and serum albumin on long-term AVF
      survival. RESULTS: A total of 137 AVFs (primary procedure in 84 and as a
      secondary procedure in 53 cases) at the elbow were performed in 130 patients; 7
      patients had AVFs attempted at both elbows. The mean age was 56.57 yr with a mean
      follow-up of 48.54 months. Twenty-two patients died with a functioning AVF, while
      7 patients also with a functioning AVF received a renal transplant. Overall 74%
      of AVF were patent at the end of 1 yr, while 22.5% failed or did not mature
      immediately after the procedure. Two patients had their AVFs tied off due to
      steal syndrome. Of the various factors known to affect long-term survival of AVF
      in patients receiving haemodialysis, only plasma albumin > 35 g/L was associated
      with poorer long-term patency in our study. CONCLUSION: Our report supports the
      view that AVF at the elbow may obviate the disadvantages of AVF at the wrist in
      elderly patients, females and in diabetics. In this group of patients it may be
      preferable to create a primary AVF at the elbow rather than the wrist. Patients
      who have a failed attempt at creating an AVF at the wrist should undergo AVF at
      the elbow before the placement of a synthetic graft. This strategy will result in
      saving time and avoid multiple operations. There may also be a reduction in the
      use of synthetic grafts resulting in cost savings and avoiding the complications
      associated with synthetic grafts.

PMID- 10945203
TI  - A comparison of prednisolone and methylprednisolone for renal transplantation.
AB  - A large difference in immunosuppressive potency between methylprednisolone and
      prednisolone has been suggested in vitro. However, the selection of the best
      glucocorticoid for renal transplantation has been seldom considered so far. Thus,
      the present study was undertaken to compare therapeutic efficacy between
      prednisolone and methylprednisolone in renal transplantation. We studied 42 renal
      transplant recipients who were operated on between 1990 and 1994. The patients
      were divided into two treatment groups: a methylprednisolone/ cyclosporine group
      (n = 19) and a prednisolone/cyclosporine group (n = 23). Clinical outcome and
      drug side effects were compared retrospectively between the treatment groups 24
      84 months after transplantation. The overall graft survival time in patients
      treated with methylprednisolone/cyclosporine was superior to that in patients
      treated with prednisolone/cyclosporine (p < 0.05). Among the recipients from
      cadaver donors, 5/16 (31.3%) treated with prednisolone required nephrectomy,
      whereas none of the 10 patients treated with methylprednisolone received
      nephrectomy (p < 0.01). An examination of the recipients from living related
      donors revealed that serum creatinine levels 24-36 months after operation were
      significantly lower in the methylprednisolone group (p < 0.05). Cyclosporine
      trough levels and glucocorticoid side effects were similar between the treatment
      groups. The results raised the possibility that methylprednisolone is superior to
      prednisolone when combined with cyclosporine for maintenance immunosuppressive
      therapy in renal transplantation.

PMID- 10945204
TI  - Efficacy and safety of amphotericin B lipid complex injection (ABLC) in solid
      organ transplant recipients with invasive fungal infections.
AB  - BACKGROUND: Fungal infections following solid-organ transplantation are a major
      source of morbidity and mortality. This report describes the efficacy and safety
      of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant
      recipients. METHODS: Three open-label, second-line treatment studies evaluated
      ABLC as a treatment for severe, life-threatening mycoses in patients who were
      refractory to or intolerant to conventional antifungal (mostly amphotericin B
      [AmB]) therapy or had pre-existing renal disease. RESULTS: The 79 solid-organ
      transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1
      pancreas) who received ABLC in these studies had the following fungal infections:
      aspergillosis (n = 39); candidiasis (n = 20); zygomycosis (n = 8); cryptococcosis
      and histoplasmosis (n = 3 each); and blastomycosis, cladosporiosis, fusariosis,
      Bipolaris hawaiiensis, Dactylaria gallopava, and an unspecified fungal infection
      (n = 1 each). The median duration of ABLC therapy was 28 d (1-178 d). The daily
      dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response
      rate for the patients who could be assessed was 58% (39/67). Clinical response
      rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%,
      respectively; response rates for aspergillosis and candidiasis were 47 and 71%,
      respectively. Forty-six of the 79 patients (58%) survived for more than 28 d
      after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64
      patients (81%) had stable (n = 37) or improved (n = 27) serum creatinine at the
      end of treatment. CONCLUSIONS: ABLC is safe and effective treatment for fungal
      infections in solid-organ transplant recipients. Its renal-sparing properties are
      particularly suited for this high-risk population for renal failure.

PMID- 10945205
TI  - A single center's clinical experience with quadruple immunosuppression including
      ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas-kidney
      transplants.
AB  - Acute rejection remains a major problem in simultaneous pancreas-kidney (SPK)
      transplant and occurs in 60-100% of the cases. With the introduction of
      mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis
      immunosuppressant, reduced rates of rejection have been reported. This study
      investigates the frequency and clinical relevance of allograft rejection in SPK
      patients receiving antithymocyte globulin (ATG) or Basiliximab induction therapy
      and cyclosporine Neoral (CyA), MMF, steroid basis immunosuppression. Between
      December 1996 and October 1999, 21 consecutive patients (15 males, 6 females)
      received a SPK transplant at our institution with a mean +/- standard deviation
      (SD) age of 42 +/- 6 yr. Of these, 14 patients were treated with anti-thymocyte
      globulin (ATG) Fresenius (rabbit) 3-5 mg/kg for 6 +/- 2 d, cyclosporine Neoral
      (CyA) (trough levels 350-400 ng/mL), MMF 3 g/d and low dose steroid therapy.
      Seven SPK patients were treated with Basiliximab (Simulect, Novartis 20 mg on d 0
      and d 4 post-transplant) instead of ATG. The patients had an average human
      leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All
      patients remained on triple drug therapy. Three patients were switched to
      tacrolimus instead of Neoral for CyA intolerance. The mean +/- SD cold ischemia
      time (CIT) of the organs was 10.1 +/- 2.4 h for the pancreas and 10.5 +/- 2.6 h
      for the kidney. RESULTS: Biopsy-proven rejection occurred in the kidney of 1 ATG
      patient (8%), which responded to steroid bolus therapy. One of the patients (14%)
      with Basiliximab induction developed renal allograft rejection, which was
      resolved after a 6-d course of anti-CD3 mAb (OKT3) treatment. All patients (100%)
      were free from rejection in the pancreas, as measured by urine amylase levels and
      glycemic control without the need for exogenous insulin with a mean glycosylated
      hemoglobin (HBA1C) of 5.1 +/- 0.7%, and serum creatinine with a mean of 1.24 +/-
      0.24 mg/dL in a mean follow-up period of 17 +/- 15 months (median 12, range 2
      37). CONCLUSION: Triple drug immunosuppression including cyclosporine, MMF and
      low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction
      therapy appears to be a very suitable immunosuppressive regimen for combined
      pancreas-kidney transplant (PKT) with a marked reduction in the incidence of
      rejection.

PMID- 10945206
TI  - Microchimerism and rejection: a meta-analysis.
AB  - AIMS: To study the relationship between graft rejection and microchimerism with
      and without donor bone marrow infusion in recipients of kidney, liver, heart and
      lung transplants. Selection of manuscripts. Thirty-seven manuscripts presenting
      clinical data on microchimerism and rejection, published between 1991 and 1997,
      were identified. Of these, 16 were excluded due to duplication or insufficient
      data. Inclusion criteria were data on microchimerism, bone marrow infusion and
      rejection episodes. STATISTICAL TESTS: A mixed effect logistic model was used to
      test for homogeneity of transplant centers. The centers were found to be
      homogeneous for rejection rates controlling for microchimerism and bone marrow
      infusion. Using rejection episodes at 3, 6, and 12 months post-transplant as the
      outcome, we evaluated logistic regression models to derive odds ratios for
      rejection with microchimerism and with bone marrow infusion for each organ.
      RESULTS: Microchimerism was generally associated with a higher incidence of acute
      rejection for heart, lung, and kidney transplants and a lower incidence for liver
      transplants, especially at 12 months and above. Bone marrow infusion decreased
      the risk of acute rejection for heart transplants and increased the risk for lung
      and, to a lesser extent, for liver transplants. No consistent effect was seen in
      kidney transplants. At 12 months and longer, microchimerism was associated with a
      decreased incidence of chronic rejection in recipients of lung transplants, but
      there were insufficient data to determine this outcome for other organs.
      CONCLUSIONS: (i) Microchimerism was detected in the majority of patients. (ii)
      The effect of microchimerism and bone marrow infusion on rejection episodes
      varied with the organ and, for a given organ, it was time-dependent. (iii) These
      findings demonstrate the need for more extensive studies on microchimerism and
      donor-specific hyporesponsiveness.

PMID- 10945207
TI  - Microchimerism, macrochimerism, and tolerance.

PMID- 10945208
TI  - International sharing of split liver grafts in Asia: initial experience.
AB  - The donor shortage problem is particularly serious in Asia and has markedly
      limited progress in liver transplantation. The increasing demand has, in fact,
      made it necessary to resort to living donor liver transplantation in both
      pediatric and adult recipients. Nevertheless, expanding the use of split liver
      allografts is yet another option to increase the supply. This has a wide
      potential application on a regional level because most liver transplant programs
      are still small and may have limited resources in terms of being able to do two
      transplants in one sitting. The first experience of overseas sharing of split
      liver grafts in Asia took place in January 1999. The graft was from a 35-yr-old
      donor from Kaohsiung, Taiwan, who sustained irreversible brain damage in a
      vehicular accident and had optimal conditions for multiorgan donation. The liver
      was split ex vivo and the left lateral segment was given to a 3-yr-old girl with
      biliary atresia at the Chang Gung Memorial Hospital. The extended right lobe
      split graft was transported to Hong Kong and transplanted into a 51-yr-old male
      patient with end-stage hepatitis C cirrhosis who was then in a state of acute
      failure with hepatorenal syndrome. Graft function was excellent in both
      recipients and the patient from Taiwan was discharged without any complications.
      Unfortunately, the Hong Kong recipient developed a cerebrovascular accident and
      required a reoperation for bile leakage from the cut surface of the liver in the
      early postoperative period. He has made a steady recovery since then; graft
      function has remained good and his kidneys have recovered. Both patients are
      currently alive and well 11 months post-transplant. This initial experience of
      overseas sharing of split liver grafts in Asia demonstrates its feasibility. It
      has a potentially wide applicability and could lead to the establishment of a
      formal organ-sharing network in the region. Established competence and mutual
      trust among the participating liver transplant teams would be essential in
      perpetuating such a graft-multiplying strategy on an organized basis.

PMID- 10945209
TI  - An absent inferior vena cava in a pediatric renal transplant recipient.

PMID- 10945210
TI  - Cell-specific expression of the mercury-insensitive plasma-membrane aquaporin
      NtAQP1 from Nicotiana tabacum.
AB  - The aquaporin NtAQP1 from Nicotiana tabacum L. is insensitive to heavy-metal
      ions. In addition to water, the transport of urea or glycerol is facilitated by
      this plasma-membrane-located water channel. Northern hybridization and whole
      mount in situ hybridization revealed a high steady-state level of NtAQP1-RNA in
      roots, a decreased content in shoots and a low content in leaves. By
      immunolocalization with an antibody targeted to the N-terminus of the aquaporin,
      the localization of NtAQP1-protein at sites of expected high water transport
      rates from and to the apoplast or symplast could be demonstrated. The specific
      pattern of NtAQP1 distribution in petioles strongly indicates a transcellular
      movement of water.

PMID- 10945211
TI  - The H1 histone variant of tomato, H1-S, is targeted to the nucleus and
      accumulates in chromatin in response to water-deficit stress.
AB  - Water deficit has a significant impact on patterns of gene expression. Based on
      the deduced amino acid sequence, it has been proposed that the drought and
      abscisic acid-induced gene (his1-s) of tomato (Lycopersicon esculentum Mill.)
      encodes an H1 histone variant. To study the role of H1-S it is important to
      understand the expression characteristics of the protein. To identify the his1-s
      product in vivo the his1-s cDNA was fused to a (His)6 tag and overexpressed in
      Escherichia coli. The H1-S fusion protein was used to generate an antibody that
      recognized a protein with an apparent molecular weight of 31 kDa that accumulates
      in response to water deficit in the whole plant and detached leaves. A time
      course of his1-s expression showed that protein accumulation is delayed compared
      to the mRNA accumulation in both the whole plant and detached leaves. Cellular
      fractionation, immunofluorescence and H1-S::beta-glucuronidase fusion analyses in
      transgenic tissues were used to determine the cellular localization of H1-S. The
      results showed that H1-S accumulates in nuclei and is associated with chromatin
      of wilted tomato leaves. The drought- and abscisic acid-induced gene his1-s
      encodes a linker-histone subtype specifically accumulated in the nuclei and
      chromatin of tomato leaves subjected to water-deficit conditions. Although the
      molecular mechanism of H1-S function is still unclear, the expression
      characteristics of H1-S are consistent with a potential role of this protein in
      the regulation of gene expression in response to water deficit.

PMID- 10945212
TI  - Farnesylation is involved in meristem organization in Arabidopsis.
AB  - Although studies in plant and animal cell culture systems indicate farnesylation
      is required for normal cell cycle progression, how this lipid modification of
      select proteins translates into whole-organism developmental decisions involving
      cell proliferation or differentiation is largely unknown. The era1 mutant of the
      higher plant Arabidopsis thaliana (L.) Heynh. offers a unique opportunity to
      understand the role farnesylation may play in regulating various processes during
      the development of a multicellular organism. Loss of farnesylation affects many
      aspects of Arabidopsis growth and development. In particular, apical and axillary
      meristem development is altered and these phenotypes are contingent on the growth
      conditions.

PMID- 10945213
TI  - Clonal analysis of the Arabidopsis root confirms that position, not lineage,
      determines cell fate.
AB  - The cellular organization of the Arabidopsis thaliana (L.) Heynh. root meristem
      suggests that a regular pattern of cell divisions occurs in the root tip.
      Deviations from this pattern of division might be expected to disrupt the
      organization of cells and tissues in the root. A clonal analysis of the 3-d-old
      primary root meristem was carried out to determine if there is variability in
      division patterns, and if so to discover their effect on cellular organization in
      the root. Clones induced in the seedling meristem largely confirmed the predicted
      pattern of cell divisions. However, the cellular initials that normally give rise
      to the different cell files in the root were shown to exhibit some instability.
      For example, it was calculated that a lateral root cap/epidermal initial is
      displaced every 13 d. Furthermore, the existence of large marked clones that
      included more than two adjacent cell layers suggests that intrusive growth
      followed by cell division may occur at low frequency, perhaps in response to
      local cell deaths in the meristem. These findings support the view that even in
      plant organs with stereotypical cell division patterns, positional information is
      still the key determinant of cell fate.

PMID- 10945214
TI  - In-vitro selection of Vitis vinifera 'Chardonnay' with Elsinoe ampelina culture
      filtrate is accompanied by fungal resistance and enhanced secretion of chitinase.
AB  - Proembryogenic masses of grapevine (Vitis vinifera L.) 'Chardonnay' (clone 02Ch)
      were exposed to the culture filtrate of Elsinoe ampelina (deBary) Shear, the
      causal agent of anthracnose disease. After four or five cycles of recurrent in
      vitro selection with medium containing 40% fungal culture filtrate, putative
      resistant lines RC1 and RC2 respectively, were established. The selected lines
      inhibited the growth of E. ampelina and Fusarium oxysporium (Schlecht.) (isolated
      from watermelon) in a dual-culture assay and reduced the growth of mycelium on a
      conditioned-medium test, thus suggesting the involvement of extracellular
      compounds in resistance. Sodium dodecyl sulfate-polyacrylamide (SDS-PAGE) gel
      electrophoresis of extracellular proteins from spent suspension-culture medium
      showed enhanced secretion of new proteins by selected lines. A 36-kDa protein was
      immunodetected by a chitinase antiserum. This chitinase continued to express
      constitutively in differentiated somatic embryos and also in the intercellular
      fluids of plants regenerated from the selected lines. Somatic embryos from
      selected lines grew uninhibitedly in a medium containing 40% fungal culture
      filtrate, whereas non-selected (control) somatic embryos became necrotic and died
      within a few days. Plants regenerated from selected lines exhibited resistance to
      infection by E. ampelina in both greenhouse tests and detached leaf bioassays.
      Results suggest that embryogenic cells can be selected for resistance following
      in-vitro selection, resulting in resistant plants. Whether or not resistant cells
      pre-existed in the original embryogenic culture or were induced by the selection
      pressure could not be determined.

PMID- 10945215
TI  - Increases in cytosolic Ca2+ are not required for abscisic acid-inhibition of
      inward K+ currents in guard cells of Vicia faba L.
AB  - The inward K+ channels (IKin) of guard cells are inhibited upon application of
      abscisic acid (ABA). It has been postulated that I(Kin) inhibition requires an
      elevation in cytosolic free Ca2+ levels ([Ca2+]c) because: (i) experimental
      increases in [Ca2+]c can mimic the ABA effect, and; (ii) ABA can trigger an
      elevation of [Ca2+]c in guard cells. However, not all guard cells respond to ABA
      with a [Ca2+]c increase, and the magnitude of the increases that do occur is
      variable. Therefore, an obligate role for Ca2+ in the regulation of downstream
      effectors of ABA response, such as the I(Kin) channels, remains in question. In
      this study, we developed a methodology for simultaneous patch clamping and
      confocal ratiometric Ca2+ imaging of Vicia faba L. guard-cell protoplasts. This
      allowed us to directly assess the relationship between ABA-induced changes in
      [Ca2+]c and I(Kin) inhibition. In the presence of extracellular Ca2+, the extent
      of [Ca2+]c elevation correlated with the extent of I(Kin) inhibition. However,
      upon chelation of either extracellular Ca2+, [Ca2+]c or both, extracellular Ca2+
      and [Ca2+]c, [Ca2+]c elevation did not occur in response to ABA yet I(Kin)
      currents were still strongly inhibited. These data illustrate that Ca2+
      independent regulation is involved in ABA-inhibition of stomatal opening
      processes.

PMID- 10945216
TI  - Altered exopolysaccharides of Bradyrhizobium japonicum mutants correlate with
      impaired soybean lectin binding, but not with effective nodule formation.
AB  - The exact mechanism(s) of infection and symbiotic development between rhizobia
      and legumes is not yet known, but changes in rhizobial exopolysaccharides (EPSs)
      affect both infection and nodule development of the legume host. Early events in
      the symbiotic process between Bradyrhizobium japonicum and soybean (Glycine max
      [L.] Merr.) were studied using two mutants, defective in soybean lectin (SBL)
      binding, which had been generated from B. japonicum 2143 (USDA 3I-1b-143
      derivative) by Tn5 mutagenesis. In addition to their SBL-binding deficiency,
      these mutants produced less EPS than the parental strain. The composition of EPS
      varied with the genotype and with the carbon source used for growth. When grown
      on arabinose, gluconate, or mannitol, the wild-type parental strain, B. japonicum
      2143, produced EPS typical of DNA homology group I Bradyrhizobium, designated EPS
      I. When grown on malate, strain 2143 produced a different EPS composed only of
      galactose and its acetylated derivative and designated EPS II. Mutant 1252
      produced EPS II when grown on arabinose or malate, but when grown on gluconate or
      mannitol, mutant 1252 produced a different EPS comprised of glucose, galactose,
      xylose and glucuronic acid (1:5:1:1) and designated EPS III. Mutant 1251, grown
      on any of these carbon sources, produced EPS III. The EPS of strain 2143 and
      mutant 1252 contained SBL-binding polysaccharide. The amount of the SBL-binding
      polysaccharide produced by mutant 1252 varied with the carbon source used for
      growth. The capsular polysaccharide (CPS) produced by strain 2143 during growth
      on arabinose, gluconate or mannitol, showed a high level of SBL binding, whereas
      CPS produced during growth of strain 2143 on malate showed a low level of SBL
      binding. However, the change in EPS composition and SBL binding of strain 2143
      grown on malate did not affect the wild-type nodulation and nitrogen fixation
      phenotype of 2143. Mutant 1251, which produced EPS III, nodulated 2 d later than
      parental strain 2143, but formed effective, nitrogen-fixing tap root nodules.
      Mutant 1252, which produced either EPS II or III, however nodulated 5-6 d later
      and formed few and ineffective tap root nodules. Restoration of EPS I production
      in mutant 1252 correlated with restored SBL binding, but not with wild-type
      nodulation and nitrogen fixation.

PMID- 10945217
TI  - Developing prolamine protein bodies are associated with the cortical cytoskeleton
      in rice endosperm cells.
AB  - The mRNAs that encode the prolamine storage proteins in rice (Oryza sativa L.)
      endosperm cells are enriched on the surface of the prolamine protein bodies
      (PBs), a subcellular structure consisting of a prolamine intracisternal granule
      surrounded by rough endoplasmic reticulum membrane. Previous biochemical studies
      (D.G. Muench et al., 1998, Plant Physiol. 116: 559-569) have shown that prolamine
      mRNAs may be anchored to the PB surface via the cytoskeleton. To better
      understand the mechanism and role of mRNA localization in rice endosperm cells,
      we studied the subcellular development of prolamine PBs and their relationship
      with the cytoskeleton in rice endosperm cells. Confocal microscopy of endosperm
      cells showed that, unlike the glutelin PBs, the developing prolamine PBs are not
      randomly distributed within the cell, but instead are often enriched in the
      cortical region of the cell only a few micrometers beneath the plasma membrane.
      In addition, the peripheral prolamine PBs are closely associated with the
      cortical microtubule and actin filament networks. The cortical enrichment of rice
      prolamine protein bodies represents a unique example of endoplasmic reticulum
      subdomain localization in plant cells. The interaction of this endoplasmic
      reticulum subdomain with the cytoskeleton provides new insights on the possible
      mechanism and role of mRNA localization in plants.

PMID- 10945218
TI  - Biosynthesis of spermidine, a direct precursor of pyrrolizidine alkaloids in root
      cultures of Senecio vulgaris L.
AB  - The polyamine spermidine is an essential biosynthetic precursor of pyrrolizidine
      alkaloids. It provides its aminobutyl group which is transferred to putrescine
      yielding homospermidine, the specific building block of the necine base moiety of
      pyrrolizidine alkaloids. The enzymatic formation of spermidine was studied in
      relation to the unique role of this polyamine as an alkaloid precursor. S
      adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.50) and spermidine synthase
      (SPDS, EC 2.5.1.16) from root cultures of Senecio vulgaris were partially
      purified and characterized. The SAMDC-catalyzed reaction showed a pH optimum of
      7.5, that of SPDS an optimum of 7.7. The Km value of SAMDC for its substrate S
      adenosylmethionine (SAM) was 15 microM, while the apparent Km values of SPDS for
      its substrates decarboxylated SAM (dSAM) and putrescine were 4 microM and 21
      microM, respectively. The relative molecular masses of the two enzymes,
      determined by gel filtration, were 29000 (SAMDC) and 37000 (SPDS). Studies with
      various potential inhibitors revealed, for most inhibitors, profiles that were
      similar to those established with the respective enzymes from other plant
      sources. However, putrescine which is not known to be an inhibitor of plant
      SAMDC, strongly inhibited the enzyme from S. vulgaris roots. Spermidine synthase
      was sensitive to inhibition by its product spermidine. In the presence of the
      stationary tissue concentrations of the two polyamines (ca. 0.1 mM each) the
      activities of SAMDC and SPDS would be inhibited by >80%. The results are
      discussed in relation to the role of spermidine in primary and secondary
      metabolism of alkaloid-producing S. vulgaris root cultures.

PMID- 10945219
TI  - pH regulation in apoplastic and cytoplasmic cell compartments of leaves.
AB  - The regulation of pH in the apoplast, cytosol and chloroplasts of intact leaves
      was studied by means of fluorescent pH indicators and as a response of
      photosynthesis to acid stress. The apoplastic pH increased under anaerobiosis.
      Aeration reversed this effect. Apoplastic responses to CO2, HCl or NH3 differed
      considerably. Whereas HCl and ammonia caused rapid acidification or
      alkalinization, the return to initial pH values was slow after cessation of
      fumigation. Addition of CO2 either did not produce the acidification expected on
      the basis of known apoplastic buffering or even caused some alkalinization.
      Removal of CO2 shifted the apoplastic pH into the alkaline range before the pH
      returned to initial steady-state levels. In the presence of vanadate, the
      alkaline shift was absent and the apoplastic pH returned slowly to the initial
      level when CO2 was removed from the atmosphere. In contrast to the response of
      the apoplast, anaerobiosis acidified the cytosol or, in some species, had little
      effect on its pH. Acidification was rapidly reversed upon re-admission of oxygen.
      The CO2-dependent pH changes were very fast in the cytosol. Considerable
      alkalinization was observed after removal of CO2 under aerobic, but not under
      anaerobic conditions. Rates of the re-entry of protons into the cytosol during
      recovery from CO2 stress increased in the presence of oxygen with the length of
      previous exposure to high CO2. Effective pH regulation in the chloroplasts was
      indicated by the recovery of photosynthesis after the transient inhibition of
      photosynthetic electron flow when CO2 was increased from 0.038% to 16% in air. As
      photosynthesis became inhibited under high CO2, reduction of the electron
      transport chain increased transiently. The time required for recovery of
      photosynthesis from inhibition during persistent CO2 stress was similar to the
      time required for establishing steady-state pH values in the cytosol under acid
      stress. The high capacity of leaf cells for the rapid re-attainment of pH
      homeostasis in the apoplast and the cytoplasm under acid or alkaline stress
      suggested the rapid activation or deactivation of membrane-localised proton
      transporting enzymes and corresponding ion channel regulation for co-transport of
      anions or counter-transport of cations together with proton fluxes. Acidification
      of the cytoplasm appeared to activate energy-dependent proton export primarily
      into the vacuoles whereas apoplastic alkalinization resulted in the pumping of
      protons into the apoplast. Proton export rates from the cytosol into the apoplast
      after anaerobiosis were about 100 nmol (m2 leaf area)(-1) s(-1) or less. Proton
      export under acid stress into the vacuole was about 1200 nmol m(-2) s(-1). The
      kinetics of pH responses to the addition or withdrawal of CO2 indicated the
      presence of carbonic anhydrase in the cytosol, but not in the apoplast.

PMID- 10945220
TI  - Identification and partial characterization of proteins and proteoglycans
      encrusting the secondary cell walls of flax fibres.
AB  - Four proteins were isolated from depectinised elementary fibres of flax (Linum
      usitatissimum L.), using either alkali or cellulase digestion treatments. All the
      four proteins were characterized by a deficiency or low contents of
      hydroxyproline and by high levels of glutamic acid/glutamine and/or aspartic
      acid/asparagine. The two proteoglycans solubilized with cellulase strongly
      reacted with beta-glucosyl Yariv reagent but not with alpha-glucosyl Yariv
      reagent and contained appreciable amounts of alanine, glycine, serine and
      threonine, suggesting a relationship with cell wall hydroxyproline-deficient
      arabinogalactan-proteins. The two alkali-extracted proteins did not show any
      reaction with beta-glucosyl Yariv dye. Due to the harsh treatment, they might
      only partially represent the original proteins. Due to its high level of glycine
      (41%), one of these proteins might be classified as a glycine-rich protein. The
      latter polypeptide, of low molecular molar mass, contained 14.6% leucine and
      might consist of a domain related to leucine-rich proteins. The data show that
      these proteins and arabinogalactan-protein-like proteoglycans were strongly
      associated with the secondary walls of flax fibres. Their presence in small
      amounts (0.1-0.4%), raises the problem of their putative structural role.

PMID- 10945221
TI  - Aberrant chloroplasts in transgenic rice plants expressing a high level of maize
      NADP-dependent malic enzyme.
AB  - NADP-dependent malic enzyme (NADP-ME) is a major decarboxylating enzyme in NADP
      ME-type C4 species such as maize and Flaveria. In this study, chloroplastic NADP
      ME was transferred to rice (Oryza sativa L.) using a chimeric gene composed of
      maize NADP-ME cDNA under the control of rice light-harvesting chlorophyll-a/b
      binding protein (Cab) promoter. There was a 20- to 70-fold increase in the NADP
      ME activity in leaves of transgenic rice compared to that in wild-type rice
      plants. Immunocytochemical studies by electron microscopy showed that maize NADP
      ME was mostly localized in chloroplasts in transgenic rice plants, and that the
      chloroplasts were agranal without thylakoid stacking. Chlorophyll content and
      photosystem II activity were inversely correlated with the level of NADP-ME
      activity. These results suggest that aberrant chloroplasts in transgenic plants
      may be caused by excessive NADP-ME activity. Based on these results and the known
      fact that only bundle sheath cells of NADP-ME species, among all three C4
      subgroups, have agranal chloroplasts, we postulate that a high level of
      chloroplastic NADP-ME activity could strongly affect the development of
      chloroplasts.

PMID- 10945222
TI  - Evidence for covalent linkage between xyloglucan and acidic pectins in suspension
      cultured rose cells.
AB  - Neutral xyloglucan was purified from the cell walls of suspension-cultured rose
      (Rosa sp. 'Paul's Scarlet') cells by alkali extraction, ethanol precipitation and
      anion-exchange chromatography on 'Q-Sepharose FastFlow'. The procedure recovered
      70% of the total xyloglucan at about 95% purity in the neutral fraction. The
      remaining 30% of the xyloglucan was anionic, as demonstrated both by anion
      exchange chromatography at pH 4.7 and by high-voltage electrophoresis at pH 6.5.
      Alkali did not cause neutral xyloglucan to become anionic, indicating that the
      anionic nature of the rose xyloglucan was not an artefact of the extraction
      procedure. Pre-incubation of neutral [3H]xyloglucan with any of ten non
      radioactive acidic polysaccharides did not cause the radioactive material to
      become anionic as judged by electrophoresis, indicating that stable complexes
      between neutral xyloglucan and acidic polysaccharides were not readily formed in
      vitro. The anionic xyloglucan did not lose its charge in the presence of 8 M urea
      or after a second treatment with NaOH, indicating that its anionic nature was not
      due to hydrogen-bonding of xyloglucan to an acidic polymer. Proteinase did not
      affect the anionic xyloglucan, indicating that it was not associated with an
      acidic protein. Cellulase converted the anionic xyloglucan to the expected
      neutral nonasaccharide and heptasaccharide, indicating that the repeatunits of
      the xyloglucan did not contain acidic residues. Endo-polygalacturonase converted
      about 40% of the anionic xyloglucan to neutral material. Arabinanase and
      galactanase also converted appreciable proportions of the anionic xyloglucan to
      neutral material. These results show that about 30% of the xyloglucan in the cell
      walls of suspension-cultured rose cells exists in covalently-linked complexes
      with acidic pectins.

PMID- 10945223
TI  - The negative effect of nitrate on gametogenesis is independent of nitrate
      assimilation in Chlamydomonas reinhardtii.
AB  - The effect of nitrate on gamete differentiation as well as on the expression of
      genes involved in gametogenesis, nitrogen scavenging, and nitrate assimilation
      has been analyzed in wild-type and mutant strains of Chlamydomonas reinhardtii.
      Nitrate prevented gamete formation from wild-type strains and caused a strong
      reduction in the number of zygotes recovered in genetic crosses between nitrate
      assimilation-deficient mutants, thus suggesting that nitrate by itself is
      providing a negative regulatory signal for the sexual differentiation of the
      alga. Addition of nitrate at low concentrations to wild-type cells, after an
      initial period of nitrogen starvation, resulted in a drastic decrease in
      transcript levels of both nitrate-assimilation genes (NIA1 and NRT2;1) and genes
      induced after N-starvation (NCG2 and NCG4). This strong effect of nitrate was due
      to its assimilation products since it was not evident in nitrate-assimilation
      mutants. A slight negative effect of nitrate on NCG4 expression was only observed
      in the mutant. Nitrate by itself was also found to provide a negative signal for
      the expression of gamete-specific genes (GAS3 and GAS18) in mutants incapable of
      assimilating nitrate.

PMID- 10945224
TI  - Modulation of autoimmune diseases by nitric oxide.
AB  - Nitric oxide (NO) is an intercellular messenger that performs a number of
      functions, including neurotransmission, vasodilatation, inhibition of platelet
      aggregation, and modulation of leukocyte adhesion. NO has recently been shown to
      act as a potent cytotoxic effector molecule as well as to play an important role
      in the pathogenesis of organ-specific autoimmunity. NO may also modulate the
      immune response by interfering with Th1/Th2 balance in autoimmune diseases. This
      review will discuss the role of NO and nitric oxide synthase (NOS) in
      pathophysiologic and therapeutic implications in various autoimmune diseases with
      particular reference to T helper-1 (Th1) and T helper-2 (Th2) cytokines.

PMID- 10945225
TI  - DAP12 and KAP10 (DAP10)-novel transmembrane adapter proteins of the CD3zeta
      family.
AB  - Transmembrane adapter proteins are molecules that associate with receptors and
      mediate intracellular signals following interaction of the receptor with its
      ligand. Many such molecules have been characterized in detail, particularly the
      small TM adapters of the CD3zeta class at the core of the T cell receptor.
      Recently, two new genetically linked members of this class of transmembrane
      adapters have been identified called DAP12 (KARAP) and KAP10 (DAP10),
      respectively. In this review, we discuss this new class of TM adapters using the
      wealth of knowledge concerning CD3zeta and FcRgamma to highlight similarities and
      differences with DAP12 and KAP10. In addition, novel receptor families which
      interact with these TM adapters have also been identified. The role of these
      receptors and their inhibitory isoforms are discussed.

PMID- 10945227
TI  - HIV-1 gp41 and type I interferon: sequence homology and biological as well as
      clinical implications.
AB  - HIV-1 gp41-like human type I interferon (IFN) could inhibit lymphocyte
      proliferation and up-modulate MHC class I and II and ICAM-1 molecule expression.
      Sequence comparison indicates that a similar epitope RILAV-YLKD exists between N
      domain of gp41 and two regions in IFN-alpha(aa29-35 and 113-129), IFN-beta (aa31
      37 and 125-138) and IFN-omega (aa29-35 and 123-136), which was shown to form IFN
      alpha/beta-receptor binding site. Weak sequence similarity was also found to
      exist in both regions on gp41 and type I IFN of murine and bovine. Experimental
      studies indicated that a common immunological epitope exists between gp41 and IFN
      alpha and -beta. Antibodies against human IFN-alpha and -beta recognized the
      common immunological epitope and inhibited gp41-binding to the potential cellular
      receptor protein p45. Moreover, the polyclonal antibody to IFN-beta completely
      inhibited gp41-binding to human T, B cells and monocytic cells, while IFN-alpha
      could only inhibit this binding incompletely. It was interestingly observed that
      human IFN-beta after preincubating with cells could incompletely inhibit the
      binding of gp41 to human B cells and monocytic cells, and very weakly inhibit the
      binding to human T cells, indicating that the receptor for IFN-beta-binding may
      be involved in gp41 binding. This potential relationship may be based on the
      amino acid sequence homology in the receptor binding region between gp41 and IFN
      beta. It was observed that the increased levels of antibodies against human IFN
      alpha and -beta exist in HIV-1-infected individuals and are associated with the
      common epitope on gp41. Besides, several studies provided experimental evidence
      that the common immunological epitope could induce protective activity against
      HIV-1. The IFN-alpha-based vaccine has showed a significant reduction of disease
      progression in IFN-alpha-vaccine-treated HIV-infected patients. Recent
      experimental evidence indicates that gp41 and IFN-beta were involved in
      downregulation of CCR5 expression and induction of cell activation or signal
      transduction. Whether it may be performed by a similar mechanism is still to be
      investigated.

PMID- 10945228
TI  - Specific cell targeting for delivery of toxins into small-cell lung cancer using
      a streptavidin fusion protein complex.
AB  - New modalities of treatment for small-cell lung cancer (SCLC) are needed, because
      the majority of patients continue to die of disseminated disease despite an
      initial response to conventional chemotherapy. Abnormal surface expression of the
      neural-cell adhesion molecule (NCAM) has been noted to be highly associated with
      SCLC. We examined the ability and efficiency of a streptavidin-Protein A (ST-PA)
      fusion protein complexed with an anti-NCAM monoclonal antibody (Mab) to transfer
      biotinylated beta-galactosidase into human SCLC cell lines NCI-H69, NCI-H526, and
      NCI-H446. When the surface molecule NCAM was targeted with this system, more than
      99% of the targeted cells internalized and exhibited beta-galactosidase activity.
      In addition, we evaluated cytotoxic activity against SCLC lines NCI-H69 and NCI
      H526 by efficient delivery of biotinylated glucose oxidase using the same ST
      PA/anti-NCAM Mab complex. Cytotoxicity of the transduced cells (SCLC) was 10-fold
      and 100-fold greater, respectively, than the glucose oxidase control. This system
      could be widely applied for specific therapy of cancer cells by targeting unique
      surface molecules (antigens) using the corresponding Mab/ST-PA complex to
      transfer a variety of effector molecules; e.g., immunotoxic compounds, into
      target cells with a high degree of efficiency and specificity.

PMID- 10945226
TI  - The major histocompatibility complex-encoded HFE in iron homeostasis and immune
      function.
AB  - HFE is a non-classical major histocompatibility complex class I molecule that
      complexes with a beta2-microglobulin. A functional link between HFE and iron
      metabolism has been established by the discovery of a physical association
      between HFE and the transferrin receptor. By inhibiting transferrin receptor
      internalization, HFE functions as a negative modulator of transferrin receptor
      function. In addition, HFE appears to be an iron sensor that directly or
      indirectly communicates the body's iron status to T cells, which then use
      cytokines as feedback modulators to achieve iron homeostasis. A working model for
      the feedback regulatory mechanism between iron metabolism and immune function is
      proposed.

PMID- 10945229
TI  - The N-terminal domain of thyroid hormone receptor-alpha is required for its
      biological activities.
AB  - Thyroid hormone (T3) receptors (T3Rs) are ligand-modulated transcription factors
      that belong to the nuclear receptor superfamily. Whereas the well-conserved DNA
      binding domain and the relatively well-conserved ligand-binding domain in T3Rs
      have been characterized in detail, limited information is available on the
      contribution of the variable N terminus to the transcriptional properties of
      T3Rs. To gain greater insight into the function of the N terminus, we generated a
      deletion mutant of T3Ralpha, T3Ralpha-deltaN1, that lacks amino acids 7-45 and
      assessed the effect of this deletion on all known transcriptional activities of
      T3Ralpha. Despite the fact that T3Ralpha-deltaN1 was expressed and bound T3 with
      an affinity similar to that of wildtype T3Ralpha, all of its common
      transcriptional activities were lost. That is, T3Ralpha-deltaN1 did not activate
      transcription from a positive or negative T3 response element, and it could not
      interfere with AP-1 transcriptional activity. Surprisingly, T3Ralpha-deltaN1 lost
      its ability to bind DNA, which can account for its deficiencies as a
      transcriptional activator. In contrast, the ability of T3Ralpha-deltaN1 to
      interact with putative coactivators or corepressors was not significantly altered
      from that of wildtype T3Ralpha. However, overall folding of T3Ralpha-deltaN1 was
      altered, as indicated by differential sensitivity to limited protease digestion.
      These data document that the N terminus of T3Ralpha, albeit relatively short and
      representing a variable and unconserved region when compared with other nuclear
      receptors, has a critical role in proper folding of the DNA-binding domain and is
      required for the biological activities of full-length T3Ralpha.

PMID- 10945230
TI  - High-level expression of a truncated wall-associated protein A from the dental
      cariogenic Streptococcus mutans.
AB  - Streptococcus mutans plays a primary role in the formation of dental caries.
      Previously, in our laboratory, an S. mutans genomic library was prepared, and the
      wapA gene was cloned into the shuttle vector, pSA4/4B2. To generate
      overexpression of wapA and to facilitate efficient purification of the WapA
      protein for use as an immunogen, an expression vector with the strong tac
      promoter was used. In order to answer questions regarding the optimization of
      solubility and expression based on gene size or the hydrophobicity of the protein
      product, 12 truncated constructs of the wapA gene were prepared using PCR. The
      truncated products were subcloned into the pGEX-6P-1 glutathione S-transferase
      (GST) fusion vector and expressed in E. coli BL21. The fusion proteins were
      analyzed by SDS-PAGE and confirmed by analysis with anti-GST and anti-WapA
      antibodies. Our study suggests that abrogation of the wapA promoter is necessary
      for expression of this gene in this expression system. Deletion of the signal
      peptide and the hydrophobic C terminus of WapA increased expression compared with
      the full-length construct, and truncation at the protease cleavage site of the C
      terminal region greatly increased the stability of the protein without a loss in
      reactivity with the anti-WapA antibody. Western immunoblot analysis with anti
      WapA antiserum clearly showed that the majority of the epitopes of the GST-WapA
      fusions are located in the N-terminal region of WapA. The immunogenicity of the
      various WapA fusion products is being examined in mice and rats to further map
      the immunologically dominant regions of the protein. This method effectively
      increased the expression of WapA and should contribute to the further
      understanding of gene expression of E. coli, as well as aid in the
      characterization of this protein for future immunologic evaluation.

PMID- 10945231
TI  - Molecular cloning demonstrates structural features of homologous bovine
      prohormone convertases 1 and 2.
AB  - PC1 and PC2 (prohormone convertase) represent neuroendocrine members of the
      mammalian subtilisin-like family of proprotein convertases. The goal of this
      study was to compare the primary sequence motifs of bovine PC1 and PC2 with those
      of homologs from other mammalian species to establish the structural basis for
      PC1 and PC2 activities in bovine that resemble other mammalian homologs.
      Molecular cloning from bovine adrenal medulla resulted in the isolation of cDNAs
      for bovine PC1 and PC2 with highly conserved primary sequences with respect to
      signal sequence, prosegment, catalytic domain, and P domain. Bovine PC1 and PC2
      contained the catalytic triad residues Asp, His, Ser, which are identical to the
      triads in PC1 and PC2 from other mammalian species. Bovine PCl contained Asn as
      the oxyanion hole residue; in contrast, bovine PC2 contained Asp as the oxyanion
      hole residue, which is identical to PC2 in other mammalian species. Bovine PC1
      and PC2 possessed the P domain that contains the functional RRGDL motif. The
      cloned cDNAs detected expression of PC1 and PC2 mRNAs in bovine adrenal medulla.
      These results establish the defined structural domains of bovine PC1 and PC2 that
      are known to be essential for the activities of these enzymes in various species.

PMID- 10945232
TI  - Comparative study of the coupling between topoisomerase I activity and high
      mobility group proteins in E. coli and mammalian cells.
AB  - It is now well established that the HMG box DNA-binding motif can alter the
      topology of double-stranded DNA in several ways. Using the spermatid-specific
      tsHMG as a model protein of the HMG-1/-2 family, we have demonstrated that its
      expression in E. coli produces an increase in plasmid supercoiling density that
      is likely a consequence of its ability to constrain free supercoils in vivo. As
      demonstrated in vitro, stabilization of free DNA supercoils by tsHMG prevents
      topoisomerase I from gaining access to the template and could represent a
      mechanism for the apparent inhibition of topoisomerase I in bacteria. A similar
      modulation of eukaryotic topoisomerase I activity was not detected after
      expression of the tsHMG in mammalian cells. This differential response is
      discussed in terms of the marked difference in DNA packaging and accessibility of
      free supercoils in prokaryotic vs. eukaryotic cells.

PMID- 10945233
TI  - Complete genomic organization and promoter analysis of the round-spotted
      pufferfish JAK1, JAK2, JAK3, and TYK2 genes.
AB  - We have previously reported the isolation of the JAK1 gene from the round-spotted
      pufferfish. In the present study, we cloned and characterized genomic sequences
      encoding pufferfish JAK2, JAK3, and TYK2, which are other members of JAK family.
      To our knowledge, this is the first report to demonstrate the existence of four
      JAK genes in fish. All pufferfish JAK genes except JAK1 are composed of 24 exons;
      JAK1 has an additional exon. A comparison of the exon-intron organization of
      these genes revealed that the splice sites of JAK genes are nearly identical. In
      addition, all pufferfish JAK genes have one intron in the 5' untranslated region.
      Taken together, these data suggest that the pufferfish JAK genes may have evolved
      from a common ancestor. By 5' rapid amplification of cDNA ends and sequence
      analysis, we deduced the promoter regions for all JAK genes and found they do not
      contain typical TATA or CCAAT boxes but rather numerous other potential binding
      sites for transcription factors. Interestingly, the TYK2 gene is linked to CDC37
      in a head-to-tail manner with a small intergenic region of 292 bp. Within this
      region, there are two potential binding sites for transcriptional factors such as
      c-Myb and NF-IL6. The putative promoter regions of all JAK genes were tested
      either in a carp CF cell line or in zebrafish embryos using CAT or lacZ as
      reporter genes. Both assays confirmed the transcriptional activities of these
      promoters in vitro and in vivo.

PMID- 10945234
TI  - Loss control of Mcm5 interaction with chromatin in cdc6-1 mutated in CDC-NTP
      motif.
AB  - Saccharomyces cerevisiae Cdc6 plays an essential role in establishing and
      maintaining the prereplicative complex (pre-RC) by interacting with the origin
      recognition complex (ORC) and associating with chromatin origins. These
      interactions are required to load minichromosome maintenance proteins (MCMs) and
      other initiator proteins onto replication origins. Although the temperature
      sensitive cdc6 mutant, cdc6-1, has been widely used for these studies, the
      molecular mechanism of the cdc6-1 mutation has been unclear. In this study, we
      have identified a base substitution at Gly260-->Asp, near the CDC-NTP motif.
      Using a chromatin immunoprecipitation assay (CHIP), we found that cdc6-1 fails to
      load Mcm5 onto the replication origins. Chromatin fractions were used to study
      Mcm5 binding in both the wildtype and mutant background. These studies indicated
      that Cdc6 is also involved in unloading Mcm5 from chromatin. Specifically, the
      cdc6-1 mutation protein, cdc6(G260D), which failed to load Mcm5 onto replication
      origins, also failed to unload the Mcm5 protein. Furthermore, the overexpression
      of wildtype CDC6 accelerated the unloading of Mcm5 from chromatin fractions. In
      the absence of functional Cdc6, the Mcm5 protein showed nonorigin binding to
      chromatin with the cell cycle arrested at the G1S phase transition. Our results
      suggested that the cdc6(G260D) mutant protein fails to assemble an operational
      replicative complex and that wildtype Cdc6 plays a role in preventing re
      replication by controlling the unloading the MCMs from chromatin origins.

PMID- 10945235
TI  - Clinical significance of the gap junction in the restitution of gastric mucosa.

PMID- 10945236
TI  - Chemokines, leukocytes, and atherosclerosis.

PMID- 10945237
TI  - Importance of gap junction in gastric mucosal restitution from acid-induced
      injury.
AB  - Evidence is accumulating that gap junctional intercellular communication (GJIC)
      plays an important role in the gastric mucosal defense system. This study was
      conducted to determine whether GJIC mediates a restitution process in gastric
      mucosa. Male Sprague-Dawley rats were fasted and anesthetized. Gastric injury was
      induced by luminal perfusion with 0.2N HCl for 10 minutes. Mucosal integrity was
      continuously monitored by measuring the clearance of chromium 51-labeled
      ethylenediaminetetraacetic acid, which was used for analysis of recovery from the
      injury. Perfusion with 0.25% octanol (OCT; inhibitor of GJIC) was started after
      acid injury to assess its effect on restitution. The effect of irsogladine (IG;
      activator of GJIC) was also tested. Gastric mucosal GJIC was
      immunohistochemically evaluated with monoclonal antibody gap junction protein
      (connexin 32). Recovery from acid-induced mucosal injury occurred rapidly when
      acid perfusion was discontinued (within about 60 minutes). OCT, which didn't
      cause any injury to normal gastric mucosa, significantly inhibited the
      restitution. IG reversed this inhibition in a dose-dependent manner. In an
      immunohistochemical study, OCT-induced damage of gap junction was demonstrated,
      but not after IG pre-treatment. These findings suggest that GJIC may play a
      critical role in restitution in rat gastric mucosa and that gap junction function
      may be one of the important factors for the mucosal defense system.

PMID- 10945238
TI  - Endothelial cell-mediated type I collagen gel contraction is regulated by hemin.
AB  - The contraction of three-dimensional type I collagen gels is regarded as a model
      of contraction during wound healing and tissue remodeling. Because such a process
      could contribute to vessel narrowing, we hypothesized that endothelial cells may
      be able to mediate gel contraction. To demonstrate this, type I collagen was
      extracted from rat tail tendon and used to prepare collagen gels. Bovine arterial
      endothelial cells (BAECs) or human pulmonary artery endothelial cells (HPAECs)
      were then plated on the top of the gels in serum-free Ham's F-12 medium or 2%
      fetal calf serum-endothelium growth medium-2 (FCS-EGM2), respectively. After 48
      hours of attachment, gels were released and floated in 0.2% FCS-Ham's F-12 medium
      (BAECs) or 2% FCS-EGM2 (HPAECs). Gel size was measured with an image analyzer
      daily for 5 consecutive days. Gels were then digested with collagenase to
      quantify DNA and hydroxyproline. BAECs contracted the gels in a time-dependent
      manner over the 5 days. Contraction was dependent on cell density (gel size was
      100% of initial size after 5 days with no cells vs. 66.4%+/-0.5% with 0.9x10(4)
      cells/cm2 and 22.1%+/-0.3% with 7.5x10(4) cells/cm2) and was inversely related to
      collagen concentration (gel size was 22.3%+/-0.05%, 46.4%+/-0.9%, 72.3%+/-0.4%,
      and 87.4% +/-0.3% of initial size for gels prepared with 0.5 mg/mL, 0.75 mg/mL, 1
      mg/mL, and 2 mg/mL of collagen, respectively). Hemin (a precursor for CO) and
      cytochalasin D inhibited collagen gel contraction mediated by both bovine and
      human endothelial cells without changing cell number or hydroxyproline content.
      In contrast, prostaglandin E2, an inhibitor, and transforming growth factor
      beta1, a stimulator of fibroblast-mediated gel contraction, had no effect on
      endothelial cell-mediated contraction. These findings demonstrate that
      endothelial cells are able to contract native type I collagen gels and that this
      process can be modulated by exogenous mediators. Such a capability may cause
      remodeling of subjacent matrix of endothelial cells and may contribute to vessel
      narrowing.

PMID- 10945239
TI  - Sialic acid content of low-density lipoprotein in women with coronary artery
      disease.
AB  - A low sialic acid content in low-density lipoprotein (LDL) has been associated
      with coronary artery disease (CAD) in studies that have included mostly male
      subjects. We compared the sialic acid-to-apolipoprotein B ratios of total LDL and
      its subfractions in middle-aged women with CAD (CAD+, n = 22) with those ratios
      in healthy female control subjects (CAD-, n = 11). CAD+ subjects had a lower
      sialic acid ratio in total LDL and in its subfractions as compared with results
      in CAD- subjects. In total, light, and dense LDL, the sialic acid ratio was
      negatively correlated with the respective cholesterol and phospholipid
      concentrations, and in very dense LDL, it was negatively correlated with
      triglyceride concentration. In multivariate analysis, CAD and LDL cholesterol
      contributed to the explanation of the variability of LDL sialic acid ratios. In
      summary, a low sialic acid-to-apolipoprotein B ratio in LDL was associated with
      the presence of CAD in middle-aged women with mild to moderate
      hypercholesterolemia.

PMID- 10945240
TI  - Simplified urinary immunoassay for 2,4-D: validation and exposure assessment.
AB  - Urinary monitoring of exposed workers by either analytic chemical methods or
      radioimmunoassay suggests that urinary levels of 2,4-dichlorophenoxyacetic acid
      (2,4-D) exceeding 30 ppb are indicative of occupational exposure. However, the
      current methods do not lend themselves to clinical laboratory use in the rural
      medical setting. The major goal of this project was to provide medical
      practitioners who care for members of the agricultural community with a cost
      efficient way to conduct exposure assessment. This project used a direct 2,4-D
      enzyme immunoassay (EIA) and measurement of the ratio between 2,4-D-spiked and
      non-spiked samples of the same urine to quantify 2,4-D levels. This simplified
      approach minimizes the effects of non-specific interfering substances in urine
      and eliminates the need for sample extraction and clean-up. Possible urine co
      contaminants (2,4-dichlorophenol and 2,5-dichlorophenol) do not significantly
      interfere with this immunoassay. Twenty-two forest pesticide applicators who
      apply and use chlorophenoxy herbicides in their work and 14 comparable control
      subjects were studied to validate the assay in the occupational setting. Coded
      urine specimens were examined for levels of 2,4-D by high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) and compared with
      immunoassay results from the same specimens. A correlation coefficient of r =
      0.982 with a P value of .0001 for a plot of HPLC-MS/MS versus immunoassay
      demonstrated that the results from these methods were comparable over urinary
      dose levels ranging from not detectable (<19 ppb) to 1700 ppb 2,4-D, as
      determined by immunoassay.

PMID- 10945241
TI  - Differential expression of canalicular membrane Ca2+/Mg(2+)-ecto-ATPase in
      estrogen-induced and obstructive cholestasis in the rat.
AB  - Extracellular adenosine triphosphate (ATP) may regulate hepatocyte and
      cholangiocyte functions, and under some conditions it may have deleterious
      effects on bile secretion and cause cholestasis. The canalicular membrane enzyme
      Ca2+/Mg2+-ecto-ATPase (ecto-ATPase) hydrolyzes ATP/adenosine diphosphate
      (ATP/ADP) and regulates hepatic extracellular ATP concentration. Changes in liver
      ecto-ATPase in estrogen-induced cholestasis were examined in male rats receiving
      17alpha-ethinylestradiol (E groups) for 1, 3, or 5 days (5 mg/kg/day, sc) and
      compared with changes in rats subjected to obstructive cholestasis (O groups) for
      1, 3, or 8 days. Activity of ecto-ATPase, protein mass in canalicular membranes
      and bile (estimated by Western blotting), steady state mRNA levels (by Northern
      blotting), and cellular and acinar distributions of the enzyme (histochemistry
      and immunocytochemistry) were assessed in these groups. Activity of ecto-ATPase,
      protein mass in isolated canalicular membranes, and enzyme mRNA levels were
      significantly increased in E group rats as compared with controls. In contrast,
      these parameters were markedly decreased in O group rats, and the enzyme protein
      was undetectable in bile. The ecto-ATPase histochemical reaction was markedly
      increased in the canalicular membrane of E group rats, extending from acinar zone
      2 to zone 1, whereas it decreased in the O group. The ecto-ATPase
      immunocytochemical reaction was present in the canalicular membrane and
      pericanalicular vesicles in control and E group hepatocytes, but it decreased in
      obstructive cholestasis and was localized only to the canalicular membrane. Thus,
      significant changes in liver ecto-ATPase were apparent in 17alpha
      ethinylestradiol-induced cholestasis that were opposite to those observed in
      obstructive cholestasis. Assuming that the alterations observed in obstructive
      cholestasis are the result of the cholestatic phenomenon, we conclude that
      changes in ecto-ATPase in 17alpha-ethinylestradiol-treated rats might be either
      primary events or part of an adaptive response in 17alpha-ethinylestradiol
      induced cholestasis.

PMID- 10945242
TI  - A non-toxic heat shock protein 70 inducer, geranyl-geranyl-acetone, restores the
      heat shock response in gastric mucosa of protein-malnourished rats.
AB  - Acute gastric mucosal lesions caused by stress or noxious stimuli are important
      to consider in the management of critically or chronically ill patients. Protein
      malnutrition has been implicated as a risk factor for stress ulcer and subsequent
      complications in those patients. When male Wistar rats fed a 5% or 20% casein
      diet for 3 weeks were exposed to restraint and water-immersion stress, the low
      protein diet significantly increased the ulcer index. The low-protein diet did
      not change the level of heat shock factor 1 (HSF1) in gastric mucosa but it did
      attenuate the HSF1 activation after exposure to the stress, resulting in the
      inhibition of HSP70 mRNA expression and HSP70 induction in gastric mucosa. HSP70
      is crucial for the maintenance of cell integrity during pathophysiologic
      conditions; therefore the impaired HSP70 induction appeared to at least in part
      aggravate stress ulcer. We also tested whether a non-toxic HSP70 inducer, geranyl
      geranyl-acetone (GGA), effectively improved the mucosal integrity by stimulating
      HSP70 induction under protein malnutrition. Intragastric administration of GGA
      (200 mg/kg twice a day) to the protein-malnourished rats for up to 1 week failed
      to stimulate the HSP70 induction. However, the administration of GGA (200 mg/kg
      twice a day) for 3 weeks restored HSP70 induction and induced higher resistance
      against stress ulcer as compared with results in vehicle-treated, normally
      nourished rats. Our results suggest that GGA may have a potential benefit for the
      prevention of stress ulcer in chronically or critically ill patients with protein
      malnutrition.

PMID- 10945243
TI  - Examination of the mechanism of action of nitrogen monoxide on iron uptake from
      transferrin.
AB  - Nitrogen monoxide (NO) exerts many of its functions by binding to iron (Fe) in
      the active sites of a number of key proteins. Previously we have shown that NO
      produced by NO-generating agents decreased cellular Fe uptake from transferrin
      (Tf). However, the mechanism of this effect was not elucidated. In this study we
      examined the possible mechanisms whereby NO could interfere with Fe uptake. Our
      experiments demonstrate that NO produced by the NO generator S-nitroso-N
      acetylpenicillamine was slightly more effective than the Fe chelator deferoxamine
      at reducing iron 59 uptake from 59Fe-labeled Tf by LMTK- fibroblasts. Other NO
      generators including S-nitrosoglutathione (GSNO) and spermine-NONOate also
      decreased 59Fe uptake from 59Fe-labeled Tf. In contrast, precursors of these
      compounds that do not release NO had no effect. When the RAW264.7 macrophage cell
      line was activated to produce NO by incubation with lipopolysaccharide or
      lipopolysaccharide and interferon-gamma, a decrease in 59Fe uptake from 59Fe
      labeled Tf was also observed. Experiments with electron paramagnetic resonance
      spectroscopy and ultraviolet-Vis spectrophotometry demonstrated that NO did not
      prevent Fe uptake by binding to the Fe-ligating sites of Tf, suggesting that it
      acted more distally. Because the uptake of Fe is an energy-dependent process, and
      since NO inhibits mitochondrial respiration, cellular adenosine triphosphate
      (ATP) was estimated after incubation with GSNO. In the presence of D-glucose (D
      G), GSNO reduced ATP levels by 35% as compared with the control, while in the
      absence of D-G, GSNO reduced ATP by 72%. When the same experiments were performed
      with D-fructose (D-F), which cannot be efficiently metabolized by fibroblasts, no
      "rescue" effect was observed on ATP levels. The addition of D-G to GSNO prevented
      the decrease in 59Fe uptake from 59Fe-labeled Tf while D-F did not, in good
      correlation with their effects on ATP levels. These results suggest that D-G acts
      as a salvage metabolite to prevent the NO-mediated decrease in ATP levels and Fe
      uptake from Tf. Although NO could reduce Fe uptake by a number of mechanisms, the
      decrease in ATP levels appears, at least in part, to play a role. The results are
      discussed in the context of the effect of NO on cellular Fe metabolism.

PMID- 10945244
TI  - Members of the Sp transcription factor family regulate rat calmodulin gene
      expression.
AB  - We have previously demonstrated that insulin positively regulates transcription
      of the rat calmodulin (CaM) I gene and that both basal and insulin stimulation of
      this gene are critically dependent on Sp1. Furthermore, a 392 bp CaM promoter was
      stimulated by insulin equal to the full promoter but lost activity with deletion
      of any of the three Sp1 sites (Solomon SS, Palazzolo MR, Takahashi T, Raghow R.
      Endocrinology 1997;138:5052-5054). Herein we document that Sp1 preferentially
      binds to the upstream sites Sp1(2) and Sp1(3) but not Sp1(1). Furthermore, gel
      mobility super-shift assays demonstrate that both Sp1 and Sp3 protein are found
      in these complexes. When pPac-Spl, pPac-Sp3, pPac-USp3, and pPac-Sp4 were
      cotransfected with rCaM 1-392 promoter into Drosophila SL2 cells and challenged
      with 10,000 microU/mL insulin, we discovered that (1) Sp1 enhanced both basal and
      insulin-stimulated CaM I gene expression; (2) USp3, a "long" form of the Sp3
      molecule, had a stimulatory effect on CaM I gene expression; (3) Sp1 or USp3 is
      involved in mediating insulin-stimulation of the CaM I gene in SL2 cells; and (4)
      Sp3, a "short" form of the Sp3 molecule, and Sp4 inhibited Spl-stimulated and
      insulin-stimulated Sp1-mediated CaM I gene expression. Together these data
      corroborate and extend our previous observations on Sp1 and elucidate that other
      members of the Sp family of transcription factors may also be involved in
      regulating the activity of the CaM promoter.

PMID- 10945245
TI  - About the cover illustration: crop duster at work near homestead, Florida.

PMID- 10945246
TI  - Difructose anhydrides: their mass-production and physiological functions.
AB  - Difructose anhydrides (DFAs) are the smallest cyclic disaccharides consisting of
      two fructose residues, and are expected to have novel physiological functions
      from their unique structures and properties. For mass-production of alpha-D
      fructofuranose-beta-D-fructofuranose-2',1:2,3'-dianhydride (DFA III) and beta-D
      fructofuranose-beta-D-fructofuranose-2',6:2,6'-dianhydride (DFA IV), Arthrobacter
      sp. H65-7 and A. nicotinovorans GS-9 were selected as the best producers of
      inulase II, which produced DFA III from inulin and LFTase, which produced DFA IV
      from levan. The enzymes were purified and their genes were subsequently cloned
      and expressed in E. coli at higher levels than in the original bacteria. Thus, it
      became possible to provide a large amount of DFA III and DFA IV for evaluating
      their physiological properties. DFA III and DFA IV have half the sweetness of
      sucrose, but cannot be digested by the digestive system of rats. Their use by the
      intestinal microorganisms was observed in vivo even though their assimilation
      could not be detected in vitro. This implied that they were degraded by an
      unknown system in the intestine. It was also found that they affected calcium
      absorption mainly in the small intestine through mechanisms different from the
      known stimulants such as fructooligosaccharides and raffinose.

PMID- 10945247
TI  - The structural mechanism for iron uptake and release by transferrins.
AB  - Transferrins are a group of iron-binding proteins that control the levels of iron
      in the body fluids of vertebrates by their ability to bind two Fe3+ and two CO3(2
      ). The transferrin molecule, with a molecular mass of about 80 kDa, is folded
      into two similarly sized homologous N- and C-lobes that are stabilized by many
      intrachain disulfides. As observed by X-ray crystallography, each lobe is further
      divided into two similarly sized domains, domain 1 and domain 2, and an Fe3+
      binding site is within the interdomain cleft. Four of the six Fe3+ coordination
      sites are occupied by protein ligands (2 Tyr residues, 1 Asp, and 1 His) and the
      other two by a bidentate CO3(2-). Upon uptake and release of Fe3+, transferrins
      undergo a large-scale conformational change depending on a common structural
      mechanism: domains 1 and 2 rotate as rigid bodies around a rotation axis that
      passes through the two antiparallel beta-strands linking the domains. The extent
      of the rotation is, however, variable for different transferrin species and
      lobes. As a Fe3+ release mechanisms at low pH from the N-lobes of serum
      transferrin and ovotransferrin, the structural evidence for 'dilysine trigger
      mechanism' is shown. A structural mechanism for the Fe3+ release in presence of a
      non-synergistic anion is proposed on the basis of the sulfate-bound apo crystal
      structure of the ovotransferrin N-lobe. Domain-opened structures with the
      coordinated Fe3+ by the two tyrosine residues are demonstrated in fragment and
      intact forms, and their functional implications as a possible intermediate for
      iron uptake and release are discussed.

PMID- 10945248
TI  - Purification and characterization of acid-stable protopectinase produced by
      Aspergillus awamori in solid-state fermentation.
AB  - Aspergillus awamori IFO 4033 produced an acid-stable protopectinase in solid
      state fermentation using wheat bran as the medium. The enzyme was purified to a
      homogeneous preparation with anion-exchange, hydrophobic, and size-exclusion
      chromatography. The enzyme was a monomeric protein of 52 kDa, by SDS-PAGE
      analysis, with an isoelectric point of pH 3.7. The optimum pH for enzyme activity
      was 2.0, and it was most active at 50 degrees C (at pH 2.0) and was stable up to
      50 degrees C (at pH 2.0). The enzyme showed pectin-releasing activity toward
      protopectins from various origins, especially on lemon protopectin. An
      outstanding characteristic of the enzyme was its extreme stability in acidic
      conditions: the enzyme activity was not lost after incubating at pH 2.0 and 37
      degrees C for 24 h.

PMID- 10945249
TI  - NMR determination of the absolute configuration of an alpha-exo-methylene-gamma
      lactone.
AB  - Both the enantiomers of the axially chiral reagent, 2'-methoxy-1,1'-binaphthalene
      2-carbohydroximoyl chloride (MBCC), were used to convert igalan, an alpha-exo
      methylene-gamma-lactone, to yield 4,5-dihydroisoxazoles. The absolute
      configuration of igalan was determined to be (3aR,5R,6R,7aR)-6-ethenylhexahydro-6
      methyl-3-methylen e-5-(1-methylethenyl)-2(3H)-benzofuranone (IUPAC name) on the
      basis of NOE correlations in these derivatives. The absolute configurations of
      other alpha-exo-methylene-gamma-lactones can be determined by the same method.

PMID- 10945250
TI  - The characteristics and applications of recombinant cholesterol dehydrogenase.
AB  - Mass production of an r-CDH derived from Nocardia species was made possible by
      gene technology. (Horinouchi et al., Applied and Environmental Microbiology, 57,
      1386-1393 (1991)). However, the characteristics of the r-CDH have not been
      studied in detail and have not been improved enough for industrial use. We
      accordingly characterized both the native-CDH and the r-CDH prepared from
      Streptomyces lividans. Both CDHs were monomers with molecular masses of 37 kDa.
      The Km of r-CDH was 2.50 x 10(-3) M for cholesterol and 2.33 x 10(-4) M for NAD.
      The activators of CDHs were TritonX-100 and cholate. TritonX-405, Ag+, and Zn2+
      inhibited both enzymes. The residual activity of native CDH after heat treatment
      was 32% (37 degrees C, 60 min), while the r-CDH showed a residual activity of 87%
      (37 degrees C, 60 min). The r-CDH is an enzyme with high substrate specificity
      for cholesterol as well as native CDH and higher thermal stability than native
      CDH. We have developed a novel serum cholesterol assay using the r-CDH, which
      permits the direct measurement of cholesterol by measuring NADH reaction
      products. We conclude that this r-CDH enzyme is useful and can be used to measure
      cholesterol in a clinical chemistry setting.

PMID- 10945251
TI  - Isolation and characterization of low-indole-3-acetic acid-producing mutants from
      Bradyrhizobium elkanii.
AB  - We isolated 11 low-indole-3-acetic acid (IAA)-producing mutants of Bradyrhizobium
      elkanii by Tn5 mutagenesis. The amount of IAA produced by each mutant was 2.2
      13.6% of that of the wild-type. It was found by resting cell reactions that the
      biosynthetic step to convert indole-3-pyruvic acid to indole-3-acetaldehyde was
      blocked in all the mutants.

PMID- 10945252
TI  - Reversible thermal transition of soluble branched chains from slightly acid
      treated potato starch.
AB  - The reversible thermal transition of soluble branched starch chains prepared from
      slightly acid-treated potato starch granules (ATS) was investigated. Potato
      starch was immersed in 15% sulfuric acid to obtain ATS with a 1% hydrolysis rate.
      About half of the molecules of ATS, which spontaneously formed large aggregates
      with a mass of a few million daltons in aqueous solution, was fractionated and
      soluble branched starch chains with a relative molecular weight (Mr) of 8.91 x
      10(4) were obtained. Structural analysis indicated that the soluble branched
      starch chains consisted of three unit chains with Mr 7,900 and 21 unit chains
      with Mr 2,700. DSC and FT-IR measurements showed that the soluble branched starch
      chains underwent a reversible thermal transition, which is considered to be a
      helix-coil transition, during heating and cooling, but a debranched sample and
      beta-limit dextrins showed substantially different thermal behavior, indicating
      the contribution of the ordered structure of the branched chains.

PMID- 10945253
TI  - Cytochrome P4501A1-inhibitory action of antimutagenic anthraquinones in medicinal
      plants and the structure-activity relationship.
AB  - We have earlier found that flavones and flavonols in vegetables specifically
      inhibited one of the carcinogenesis-related enzymes, cytochrome P450 (CYP) 1A1,
      and subsequently suppressed the mutagenicity of food-derived carcinogens. In this
      study, we explored other candidates for the enzyme inhibitor in Chinese medicinal
      plants. Some of them were antimutagenic toward 3-amino-1-methyl-5H-pyrido[4,3
      b]indole (Trp-P-2). For example, Rheum officinale contained large amounts of
      anthraquinones as the active compounds, 3.4 mg of emodin, 2.1 mg of chrysophanol
      and 1.8 mg of rhein in 10 g of dry matter. Anthraquinones showed similar IC50
      values for antimutagenicity against Trp-P-2 to those for inhibition of the N
      hydroxylation activity of CYP1A1 toward Trp-P-2, indicating that the
      antimutagenicity was attributable to CYP inhibition. The structure-activity
      relationships were then examined with 14 commercial chemicals, and it was found
      that the interaction with an enzyme required three rings and an oxygen group in
      the side ring. This characteristic is similar to that of flavones and flavonols.

PMID- 10945254
TI  - The primary structure of the subunit in Bacillus thermoamyloliquefaciens KP1071
      molecular weight 540,000 homohexameric alpha-glucosidase II belonging to the
      glycosyl hydrolase family 31.
AB  - The gene that coded for the subunit of an molecular weight (Mr) 540,000
      homohexameric alpha-glucosidase II (alpha-D-glucoside glucohydrolase, EC
      3.2.1.20) produced by Bacillus thermoamyloliquefaciens KP1071 (FERM-P8477)
      growing at 30 to 66 degrees C was expressed in Escherichia coli HB101. The
      resulting homohexameric enzyme had a half-life of 10 min at 80 degrees C. Its
      purification and characterization showed that the enzyme was identical with the
      native one except for the latter deleting 7 N-terminal residues found in the
      former. The primary sequence of the subunit with 787 residues and an Mr of 91,070
      deduced from the gene was 24-34% identical to the corresponding sequences of 15
      alpha-glucosidases in the glycosyl hydrolase family 31 from 14 eukaryotic origins
      and the archaeon Sulfolobus solfataricus 98/2. From the sequence analysis by the
      neural network method of Rost and Sander [Rost, B. and Sander, C., Proteins:
      Struct. Funct. Genet., 19, 55-72 (1994)], we inferred that alpha-glucosidase II
      might make each subunit of 3 secondary structural regions, i.e., one N-terminal
      beta region, one central alpha/beta region with two catalytic residues Asp407 and
      Asp484, and one C-terminal beta region.

PMID- 10945255
TI  - Cloning, sequencing, and expression of the tulip bulb chitinase-1 cDNA.
AB  - A cDNA encoding tulip bulb chitinase-1 (TBC-1) was cloned using a combination of
      immunoscreening from a lambda ZAP cDNA library with anti-TBC-1 antiserum and the
      5' rapid amplification of cDNA end (RACE) method, and sequenced. The cDNA
      consists of 1,106 nucleotides and included an open reading frame encoding a
      polypeptide of 314 amino acids. Comparison of the deduced amino acid sequence and
      the determined protein sequence indicated the presence of a signal peptide and an
      extra peptide composed of 26 and 13 amino acids at the N- and C-termini,
      respectively. The deduced sequence of TBC-1 had 10-20% and 63% sequence
      similarities to plant class III chitinases and gladiolus bulb class IIIb
      chitinase (GBC-a), respectively. The cDNA encoding mature TBC-1 was amplified by
      polymerase chain reaction (PCR), ligated into the expression vector pET-22b, and
      expressed in Escherichia coli BL21(DE3). The recombinant TBC-1 (rTBC-1) expressed
      in E. coli was purified by gel filtration followed by ion-exchange
      chromatography. Specific activity of the rTBC-1 was almost same as the authentic
      TBC-1 toward glycolchitin. This is the first report on the cDNA cloning of a
      class III chitinase having C-terminal extra peptide.

PMID- 10945256
TI  - Characterization of a novel gene encoding a putative single zinc-finger protein,
      ZIM, expressed during the reproductive phase in Arabidopsis thaliana.
AB  - By differential screening of an arrayed normalized cDNA library from the
      inflorescence apex in Arabidopsis, a cDNA clone having a deduced amino acid
      sequence with a motif for a zinc finger was isolated as one of the genes
      expressed specifically in the reproductive phase. The deduced protein has a
      modular structure with a putative single C2-C2 zinc-finger motif distantly
      related to a GATA-1-type finger, a basic region with a sequence resembling a
      nuclear localization signal, and an acidic region. The gene seemed to have been
      formed by the exon-shuffling during its molecular evolution, since individual
      domains are encoded by discrete exons. RNA gel blot analysis showed its
      expression in shoot apex and flowers in the reproductive phase. The gene was
      named ZIM for Zinc-finger protein expressed in Inflorescence Meristem. The
      nuclear localization of ZIM was detected using GFP as a reporter. These results
      suggest that ZIM is a putative transcription factor involved in inflorescence and
      flower development.

PMID- 10945257
TI  - Synthesis and absolute configuration of hongoquercin B, a sesquiterpene
      substituted orsellinic acid isolated as a fungal metabolite.
AB  - (+)-Hongoquercin B (1), a weakly antibacterial fungal metabolite, was synthesized
      by starting from (S)-3-hydroxy-2,2-dimethylcyclohexanone, and its absolute
      configuration was determined as depicted by structure 1.

PMID- 10945258
TI  - Pyrithiamine resistance gene (ptrA) of Aspergillus oryzae: cloning,
      characterization and application as a dominant selectable marker for
      transformation.
AB  - A pyrithiamine (PT) resistance gene (ptrA) was cloned from a genomic DNA library
      prepared from a PT resistant mutant of Aspergillus oryzae. It conferred high
      resistance to PT on an A. oryzae industrial strain as well as A. nidulans.
      Nucleotide sequence analysis showed that the ptrA gene contained one intron (58
      bp) and encodes 327 amino acid (aa) residues. Additionally, the deduced aa
      sequence has 72% and 63% identity to Fusarium solani sti35 encoding a stress
      inducible protein and Saccharomyces cerevisiae THI4 encoding an enzyme involved
      in thiamine biosynthesis, respectively, indicating that ptrA is a mutated allele
      of a gene belonging to the THI4 family. The mutation point was identified in the
      conserved motif in 5'-flanking region of these three THI4 homologous genes (ptrA,
      sti35, and THI4). The introduction of the ptrA gene allowed an A. oryzae
      industrial strain to grow on the minimum medium containing PT (0.1 mg/l) on which
      an untransformed strain did not grow. This result indicates that the ptrA is
      applicable as a dominant selectable marker for transformation of A. oryzae.

PMID- 10945259
TI  - Isolated ricin B-chain-mediated apoptosis in U937 cells.
AB  - We have previously reported that ricin, a toxic lectin that inhibits protein
      synthesis induced apoptotic cell death. In this study, we have found that
      isolated ricin CM-B-chain, which has no effect on cellular protein synthesis,
      induced DNA fragmentation in U937 cells in a dose- and time-dependent manner,
      albeit it required a longer incubation time and higher concentration than those
      of holotoxin ricin. Z-Asp-CH2-DCB, a caspase family inhibitor and serine protease
      inhibitor, 3,4-dichloroisocoumarine (DCI) effectively inhibited the CM-B-chain
      mediated DNA fragmentation as well as in ricin. Thus, like ricin, multiple
      proteases with different substrate specificity may also be involved in the CM-B
      chain-mediated apoptotic pathway. Furthermore, BFA inhibited both ricin- and CM-B
      chain-mediated DNA fragmentation, suggesting an intracellular vesicle transport
      system through the Golgi complex may be involved in the apoptotic induction by
      these proteins as a common feature. On the other hand, cycloheximide (CHA)
      strongly increased the CM-B-chain-mediated DNA fragmentation, but inhibited ricin
      mediated DNA fragmentation. The opposite effects of CHA may reflect the
      difference in the apoptotic mechanism between ricin and CM-B-chain. In
      conclusion, our results suggest that ricin-B-chain can induce apoptosis through
      its lectin activity, but the underlying mechanism may be distinct from that of
      ricin in which the A-chain contributes profoundly to the apoptotic induction.

PMID- 10945260
TI  - Molecular cloning and overexpression of the gene encoding an NADPH-dependent
      carbonyl reductase from Candida magnoliae, involved in stereoselective reduction
      of ethyl 4-chloro-3-oxobutanoate.
AB  - An NADPH-dependent carbonyl reductase (S1) isolated from Candida magnoliae
      catalyzed the reduction of ethyl 4-chloro-3-oxobutanoate (COBE) to ethyl (S)-4
      chloro-3-hydroxybutanoate (CHBE), with a 100% enantiomeric excess, which is a
      useful chiral building block for the synthesis of pharmaceuticals. The gene
      encoding the enzyme was cloned and sequenced. The S1 gene comprises 849 bp and
      encodes a polypeptide of 30,420 Da. The deduced amino acid sequence showed a high
      degree of similarity to those of the other members of the short-chain alcohol
      dehydrogenase superfamily. The S1 gene was overexpressed in Escherichia coli
      under the control of the lac promoter. The enzyme expressed in E. coli was
      purified to homogeneity and had the same catalytic properties as the enzyme from
      C. magnoliae did. An E. coli transformant reduced COBE to 125 g/l of (S)-CHBE,
      with an optical purity of 100% enantiomeric excess, in an organic solvent two
      phase system.

PMID- 10945261
TI  - Inhibition by dietary tea polyphenols of chemical mediator release from rat
      peritoneal exudate cells.
AB  - Male Wistar rats were given purified diets containing safflower (SAF), perilla
      (PER), or palm (PAL) oils with or without 1% tea polyphenols (TP) for 3 weeks,
      and chemical mediator releasing activity from rat peritoneal exudate cells (PEC)
      was measured. Histamine releasing activity was not influenced by TP, while
      histamine release and intracellular histamine content were significantly
      increased in the PAL-fed group. On the contrary, leukotriene B4 (LTB4) release
      was significantly lower in rats fed PER than in those fed SAF and PAL, and TP
      significantly decreased the release in all fat groups. TP also significantly
      inhibited the release of LTB5, which was generated only in rats fed PER. TP
      significantly decreased the proportion of arachidonic acid (AA) in PEC in the SAF
      fed group and that of eicosapentaenoic acid (EPA), the precursor of LTB5 in the
      PER-fed group, but did not influence that of AA in the PAL- and PER-fed group.
      These results suggest that ingestion of TP improves type I allergic symptom
      through the inhibition of LT release though the inhibition by TP could not be
      totally explained by the reduction of substrate fatty acid.

PMID- 10945262
TI  - Enzymatic resolution of (+/-)-epoxy-beta-cyclogeraniol, a synthetic precursor for
      abscisic acid analogs.
AB  - Lipase-catalyzed optical resolution of (+/-)-epoxy-beta-cyclogeraniol (1), a key
      synthetic intermediate for epoxy-beta-ionylideneacetic acid, was achieved in high
      enantiomeric purity. Transesterification with vinyl acetate by using lipase P
      (Nagase) made enriched (-)-1, while hydrolysis of the corresponding acetate by
      using lipase P (Amano) afforded (+)-1 with a high E value (E = 1600).

PMID- 10945263
TI  - Biosynthesis of abscisic acid by the non-mevalonate pathway in plants, and by the
      mevalonate pathway in fungi.
AB  - The biosynthetic pathways to abscisic acid (ABA) were investigated by feeding [1
      (13)C]-D-glucose to cuttings from young tulip tree shoots and to two ABA
      producing phytopathogenic fungi. 13C-NMR spectra of the ABA samples isolated
      showed that the carbons at 1, 5, 6, 4', 7' and 9' of ABA from the tulip tree were
      labeled with 13C, while the carbons at 2, 4, 6, 1', 3', 5', 7', 8' and 9' of ABA
      from the fungi were labeled with 13C. The former corresponds to C-1 and -5 of
      isopentenyl pyrophosphate, and the latter to C-2, -4 and -5 of isopentenyl
      pyrophosphate. This finding reveals that ABA was biosynthesized by the non
      mevalonate pathway in the plant, and by the mevalonate pathway in the fungi. 13C
      Labeled beta-carotene from the tulip tree showed that the positions of the
      labeled carbons were the same as those of ABA, being consistent with the
      biosynthesis of ABA via carotenoids. Lipiferolide of the tulip tree was also
      biosynthesized by the non-mevalonate pathway.

PMID- 10945264
TI  - Dietary nucleotides increase the proportion of a TCR gammadelta+ subset of
      intraepithelial lymphocytes (IEL) and IL-7 production by intestinal epithelial
      cells (IEC); implications for modification of cellular and molecular cross-talk
      between IEL and IEC by dietary nucleotides.
AB  - We have investigated the effects of dietary nucleotides on intraepithelial
      lymphocytes (IEL) and intestinal epithelial cells (IEC) in weanling mice. The
      proportion of T-cell receptor (TCR) gammadelta+ IEL in BALB/c mice fed a diet
      supplemented with nucleotides (NT(+) diet) was significantly higher than that in
      mice fed the nucleotide-free diet, while the proportion of TCR alphabeta+ IEL in
      NT(+) diet-fed mice was significantly decreased. The change of the TCR
      alphabeta+/TCR gammadelta+ ratio was mainly observed in a CD8 alphaalpha+ subset
      of IEL. IEC from NT(+) diet-fed mice produced a higher level of IL-7, which is
      important in the development of TCR gammadelta+ IEL, than those from control diet
      fed mice. The expression levels of IL-7 and IL-2 receptors on IEL were not
      different between the two dietary groups. Our findings suggest that the increased
      population of a TCR gammadelta+ IEL subset by feeding nucleotides may be caused
      by the increased production of IL-7 by IEC.

PMID- 10945265
TI  - Effects of adding dietary lysine to a low gluten diet on the brain protein
      synthesis rate in aged rats.
AB  - The purpose of this study was to find whether the addition of dietary lysine
      affected the rate of brain protein synthesis in aged rats fed on a gluten diet.
      Experiments were done on two groups of aged rats (30 wk) given the diets
      containing 5% gluten or 5% gluten + 0.3% lysine for 10 d. The fractional rates of
      protein synthesis in brain, liver, and kidney increased with an addition of
      dietary lysine. In brain, liver, and kidney, the RNA activity [g protein
      synthesized/(g RNA x d)] was significantly correlated with the fractional rate of
      protein synthesis. The RNA concentration (mg RNA/g protein) was not related to
      the fractional rate of protein synthesis in any organ. The results suggest that
      the addition of the limiting amino acid for the low quality protein elevates the
      rate of protein synthesis in the brain of aged rats, and that RNA activity is at
      least partly related to the fractional rate of brain protein synthesis.

PMID- 10945266
TI  - Transfructosylation of thiol group by beta-fructofuranosidases.
AB  - Beta-fructofuranosidase fructosylated not only the hydroxyl group but also the
      thiol group of 2-mercaptoethanol in a transfer reaction using sucrose as a donor
      substrate. The enzymes from Candida utilis and Saccharomyces cerevisiae (bakers'
      yeast) were effective catalysts for the thio-fructofuranosylation. The thio
      fructosylation product was isolated by activated carbon chromatography and its
      structure was confirmed by Fab-mass spectrometry and NMR spectroscopy. The thio
      fructofuranoside was synthesized effectively at around 3.0 M for the acceptor
      concentration. The product increased with the sucrose concentration at least up
      to 1.9 M. O-Fructofuranoside was simultaneously synthesized at an early stage of
      the reaction, although it was hydrolyzed on further incubation. On the contrary,
      the thio-fructofuranoside accumulated efficiently after synthesis, indicating it
      was very stable against the hydrolytic action of the beta-fructofranosidase.

PMID- 10945267
TI  - Analysis of oxidation sensitivity of maleate cis-trans isomerase from Serratia
      marcescens.
AB  - The maleate cis-trans isomerase gene (maiA) from Serratia marcescens IFO3736 was
      cloned and sequenced. Serratia MaiA has 62.4% amino acid identity with
      Alcaligenes faecalis IFO13111 MaiA and 64.9% with Bacillus stearothermophilus MI
      102 MaiA. All known ten amino acid sequences of MaiA had significant conserved
      regions containing cysteine residues, which were previously suggested to be
      involved in an active site of the enzyme. The maiA gene was expressed in
      Escherichia coli, and expressed products MaiA was purified and characterized. The
      purified enzyme of strain IFO3736 showed high activity at room temperature and
      high heat stability. It also showed higher activity in the presence of high
      concentration of aspartic acid than the enzyme of A. faecalis IFO13111, but it
      was also sensitive to chemical oxidation. By amino acid composition analysis,
      cysteine, methionine, and tyrosine residues were suggested to be oxidized to
      inactivate the enzyme by chemical oxidation. To investigate the mechanism of
      chemical oxidation of the enzyme, six methionine residues in the conserved
      regions of S. marcescens MaiA were replaced with cysteine residues by site
      directed mutagenesis. The analysis of the constructed mutants suggested that the
      Met201 residue near the Cys198 residue is involved in the sensitivity of the
      enzyme to chemical oxidation.

PMID- 10945268
TI  - A novel enzyme, L-tryptophan oxidase, from a basidiomycete, Coprinus sp. SF-1:
      purification and characterization.
AB  - A basidiomycete, Coprinus sp. SF-1, was found to produce an L-Trp-oxidizing
      enzyme by screening from the culture collection of our laboratory. After
      solubilization by 1 M NaSCN from the particulate fraction of disrupted cells of
      the strain, the enzyme was purified about 76-fold to essential homogeneity. The
      enzyme had a molecular mass of about 420 kDa and the subunit molecular mass was
      68 kDa. The enzyme contained 1 mol of non-covalently bound FAD per mol of the
      subunit. It catalyzed the simultaneous reactions of oxidative deamination and
      oxygenative decarboxylation of L-Trp to form indolepyruvic acid and indole-3
      acetamide, the former of which was further oxidized to indole-3-acetic acid. The
      molar ratio of the respective reaction products was about 9:1. The enzyme
      specifically oxidized L-Trp, and slightly acted on L-Phe and L-Tyr. The Km for L
      Trp was about 0.5 mM in both oxidase and oxygenase reactions. Thus, the enzyme is
      a novel one and was tentatively designated "L-Trp oxidase (deaminating and
      decarboxylating)". The optimum pHs of oxidase and oxygenase activities were 7.0
      and 9.0, respectively. The optimum temperatures of both activities were 50
      degrees C. The enzyme was stable at pH 6.0-10.5 and below 50 degrees C, and at 4
      degrees C for 1 year.

PMID- 10945269
TI  - Expression of YAV proteins and vaccination against viral ascites among cultured
      juvenile yellowtail.
AB  - Yellowtail ascites virus (YAV) is a member of the family Birnaviridae and causes
      viral ascites among juvenile yellowtail (Seriola quinqueradiata). We have
      reported the cloning and expression of two viral cDNAs, the first being segment A
      encoding a polyprotein of viral capsid proteins (VP2 and VP3) and a protease
      (NS), and the second being VP2-epitope encoding serotype-specific epitope region
      on VP2, using a baculovirus expression system. Another viral cDNA encoding a
      polyprotein of NS and VP3 was cloned and expressed in this study. For the
      expression of NS/VP3 (YAV nt 1626 to 3066) in insect cells a 31-kDa protein,
      corresponding to VP3 was detected, indicating an appropriate posttranslational
      processing of NS/VP3 polypeptide by NS protease itself. The analysis of the N
      terminal amino acid sequence of this protein showed that NS protease may cleave
      an Ala-Ser bond. A study of the potential for vaccination of yellowtail fry by
      injection of insect cell lysates infected with baculovirus, containing either
      cDNA of segment A, VP2-epitope, or NS/VP3 was undertaken. Only a vaccination with
      cell lysates infected with a recombinant virus carrying the full length of YAV
      segment A gene demonstrated approximately the same effect as that of inactivated
      YAV. This result suggested that all proteins VP2, VP3, and NS are required for an
      effective vaccination.

PMID- 10945270
TI  - Distribution and properties of endo-beta-1,4-glucanase from a lower termite,
      Coptotermes formosanus (Shiraki).
AB  - A multi-enzyme distribution of endo-beta-1,4-glucanase activity was found in the
      digestive system of a worker caste of the lower termite Coptotermes formosanus
      (Shiraki) by zymogram analysis. Its distribution analysis demonstrated that about
      80% of this activity was localized in salivary glands from where only one
      component (EG-E) was secreted into the digestive tract. EG-E was isolated by a
      combination of chromatographic and electrophoretic techniques. Its molecular
      mass, optimal pH and temperature, isoelectric point, and Km were 48 kDa, 6.0, 50
      degrees C, 4.2, and 3.8 (mg/ml on carboxymethylcellulose), respectively. EG-E
      hydrolyzed cellooligosaccharides with a degree of polymerization of 4 and larger,
      and had low activity on crystalline cellulose. Main reaction products from low
      molecular weight cellulose were cellobiose and cellotriose. The N-terminal amino
      acid sequence of EG-E has similarity with fungal endo-beta-1,4-glucanases and
      cellobiohydrolases of the glycosyl hydrolase family 7 rather than the other
      insect endo-beta-1,4-glucanases of family 9.

PMID- 10945271
TI  - Inhibition of wheat leaf nitrate reductase activity by phenolic compounds.
AB  - Phenolic acids inhibited the activities of wheat leaf nitrate reductase depending
      on phenolic structure and concentration. Possible conformational change(s) in the
      enzyme induced by hydrogen bonding and/or hydrophobic interactions might be the
      cause of the enzyme inhibition. NADH:cytochrome C reductase partial activity was
      unaffected, which indicates that terminal nitrate-reducing domain of NR may be
      the site of polyphenol binding.

PMID- 10945272
TI  - Paeonilide, a novel anti-PAF-active monoterpenoid-derived metabolite from Paeonia
      delavayi.
AB  - A novel monoterpenoid-derived metabolite, paeonilide, was isolated from the roots
      of Paeonia delavayi. Its structure was established by a combination of
      spectroscopic and X-ray crystallographic analyses. It showed an anti-PAF effect
      with an IC50 value of ca. 8 microg/ml.

PMID- 10945273
TI  - Control of Pythium root rot on hydroponically grown cucumbers with silver-coated
      cloth.
AB  - Silver-coated cloth (SCC) effectively controlled root rot that was caused by
      Pythium aphanidermatum in hydroponically grown cucumber plants. The presence of
      SCC in the hydroponic solution reduced the root rot from 100% to 10% 20 days
      after inoculation with zoospores of P. aphanidermatum. It was suggested that the
      inhibition of SCC was caused not only by the silver ion dissolved from SCC, but
      also by the metallic silver and silver compounds formed on the surface of the
      root.

PMID- 10945274
TI  - Effect of the azetidine and azocine rings of okaramine B on insecticidal
      activity.
AB  - Four degraded okaramine B (2) products, 4',5'-dihydrookaramine B (3), two
      azetidine ring-opened compounds (4 and 5) and 1',2',4',5'-tetrahydrookaramine B
      (6), were prepared and their insecticidal activity was examined. Neither
      compounds 4 nor 5 showed such activity against silkworms, indicating that the
      azetidine ring moiety played an important role in the insecticidal activity.
      Moreover, both compounds 3 and 6 exhibited lower activity than 2, which means
      that the azocine ring moiety was indispensable to form the active conformation.

PMID- 10945275
TI  - Overexpression, purification, and characterization of Bacillus subtilis N
      acetylmuramoyl-L-alanine amidase CwlC.
AB  - N-acetylmuramoyl-L-alanine amidase CwlC of Bacillus subtilis was overproduced in
      Escherichia coli and purified 21-fold. The amidase hydrolyzed type A cell walls
      such as B. subtilis. The amidase bound slightly to the Microbacterium lacticum
      cell wall (type B), but did not entirely hydrolyze it. The presence of calcium or
      magnesium ion increased the resistance of the amidase to heat denaturation.

PMID- 10945276
TI  - Cloning and characterization of bovine stearoyl CoA desaturasel cDNA from adipose
      tissues.
AB  - Two overlapping cDNA clones have been isolated from bovine adipose tissue by the
      reverse-transcription-polymerase chain reaction (RT-PCR) method. The combined
      sequence of the two clones was 1039 bp in length and encoded 345 amino acids. The
      deduced amino acid sequence of the clones showed 96.5% similarity to that of
      sheep SCD and more than 88% similarities to other mammalian SCD1s, indicating
      that the clones are the cDNAs for the bovine SCD1. The transcript size of the
      bovine SCD1 was about 4.9 kb, the message was detected in the bovine adipose
      tissues but not in the liver. Female cattle expressed threefold higher levels of
      SCD1 mRNA than male animals.

PMID- 10945277
TI  - Effect of Streptococcus thermophilus on the trp-P-1 level in the blood.
AB  - We examined the 3-amino-1,4-dimethyl-5H-Pyrido-[4,3-b]indole (Trp-P-1)
      concentration in the blood after administering Trp-P-1 (0.25 mg/ml) with or
      without Streptococcus thermophilus 1131 cells (10 mg/ml) to rats. The Trp-P-1
      concentration in the blood from the portal vein was significantly lower in the
      rats that had been administered with Trp-P-1 with the strain 1131 cells than
      without them. However, there was no difference in the Trp-P-1 concentration in
      the blood taken from the abdominal aorta of these rats.

PMID- 10945278
TI  - Substrate selectivity in Aspergillus niger KU-8 acid phosphatase II using
      phosphoryl oligosaccharides.
AB  - The intracellular acid phosphatase II (ACPase II) produced by Aspergillus niger
      KU-8 preferentially dephosphorylates C-6 phosphate groups rather than C-3
      phosphate groups of phosphoryl oligosaccharides. In this study, the kinetic
      parameters of ACPase II were measured. 3(2)-phosphoryl maltotriose and 6(2)
      phosphoryl maltotriose, which differ only in the binding position of the
      phosphate group, were prepared and used as the substrates. The Km for both
      substrates were similar. However, the k(cat) value for the 6(2)-phosphoryl
      maltotriose was about three-fold of that for the 3(2)-phosphoryl maltotriose.

PMID- 10945279
TI  - Systematic isolation of highly transcribed genes in inflorescence apices in
      Arabidopsis thaliana from an equalized cDNA library.
AB  - To analyze plant meristem functions, we systematically isolated thirteen cDNA
      clones for transcripts that are highly expressed in the inflorescence apices of
      Arabidopsis by differential screening, using an equalized cDNA library with the
      clones arrayed on membranes. Their deduced amino acid sequences indicate
      important functions for proteins in determining the cell wall architecture,
      translation capacity and mitotic activity in the shoot apex during reproductive
      growth.

PMID- 10945280
TI  - Expression and secretion of scytalidopepsin B, an acid protease from Scytalidium
      lignicolum, in yeast.
AB  - An expression and secretion system for scytalidopepsin B, an acid protease from
      Scytalidium lignicolum, was constructed in yeast. Saccharomyces cerevisiae AH22
      was transformed with an yeast-E. coli shuttle vector, pAM82, in which an yeast
      invertase signal segment and the cDNA encoding the pro- and mature enzyme regions
      were inserted. The transformant was found to secret a pepstatin-insensitive acid
      protease, when cultured aerobically in a low phosphate (Pi) medium. Amino
      terminal amino acid sequencing analysis indicated that the recombinant acid
      protease was accurately processed and secreted as a mature form.

PMID- 10945281
TI  - A flexible single-step detection of blotted antigen using a fusion protein
      between protein A and green fluorescent protein.
AB  - A green fluorescent protein mutant (S147P GFP) was fused with protein A and
      expressed in Escherichia coli. This fusion protein (PA-GFP147) was used in
      immunoblotting studies as a new detection system, designated as "flexible single
      step detection (FSSD)". In FSSD, the detection of blotted antigen was done in one
      step, and the antigen-antibody reaction can be monitored by UV-irradiation in
      real time. The reaction time, therefore, can be flexibly controlled by monitoring
      the green fluorescence.

PMID- 10945282
TI  - Characteristics of foot and mouth disease virus in Taiwan.
AB  - Since March 1997 two strains of foot and mouth disease (FMD) virus have found
      their way into Taiwan, causing severe outbreaks in pigs and in Chinese yellow
      cattle. Outbreaks occurred in March 1997 were caused by a pig-adapted virus
      strain (O/Taiwan/97) which did not infect other species of cloven-hoofed animals
      by natural route. The epidemic spread over the whole region of Taiwan within two
      months and the aftermath was 6,147 pig farms infected and 3,850,746 pigs
      destroyed. In June 1999, the second strain of FMD virus (O/Taiwan/99) was
      isolated from the Chinese yellow cattle in the Kinmen Prefecture and in the
      western part of Taiwan. By the end of 1999, Chinese yellow cattle were the only
      species infected and those infected cattle did not develop pathological lesions.
      Seroconversions of serum neutralization antibody and on non-structural protein
      (NSP) antibodies were the best indicators for infection in non-vaccinated herds.
      The infected animals, however, excreted infectious levels of virus to infect new
      hosts. Based on the detection of the specific antibody to FMD virus, and virus
      isolation from oesophageal-pharyngeal (OP) fluid samples, ten herds of Chinese
      yellow cattle located in Kinmen and Taiwan were declared to have been infected.
      During the period of January to March 2000, however, five outbreaks caused by FMD
      virus similar to the O/Taiwan/99 virus occurred in four prefectures of Taiwan.
      The infected species included goats, Chinese yellow cattle and dairy cattle.
      Those outbreaks have caused high mortality in goat kids under two weeks old and
      also developed typical clinical signs of infection in dairy cattle.

PMID- 10945283
TI  - Intramammary application of ozone therapy to acute clinical mastitis in dairy
      cows.
AB  - The infusion of ozone into the inflamed quarter of cows with clinical mastitis
      was performed and the efficacy of ozone therapy was evaluated. Ozone was infused
      into the inflamed quarter via a teat canal using ozone gas generating equipment.
      Nineteen Holstein cows with acute clinical mastitis were divided into two groups:
      15 cows treated with ozone therapy, and 4 cows treated with antibiotic therapy.
      Systemic and local clinical signs, California Mastitis Test scores, the mastitis
      causing pathogens, electronic conductivity of milk, and somatic cell counts in
      milk from ozone- and antibiotic-treated quarters, were compared between the
      groups. Sixty percent (9/15) of cows with acute clinical mastitis treated with
      ozone therapy, did not require any antibiotics for recovery. This newly developed
      ozone therapy method was proven to be effective, safe, and cost effective, and
      carries no risk of drug residues in milk.

PMID- 10945284
TI  - Application of a type-specific enzyme-linked immunosorbent assay for equine
      herpesvirus types 1 and 4 (EHV-1 and -4) to horse populations inoculated with
      inactivated EHV-1 vaccine.
AB  - A type-specific enzyme-linked immunosorbent assay (ELISA) using equine
      herpesvirus types 1 (EHV-1) and 4 (EHV-4) glycoprotein G was applied for sero
      epizootiology of EHV infections in Japan. Recently, an inactivated EHV-1 vaccine
      has been administered to racehorses for prevention of upper respiratory disease.
      To examine the effect of the vaccination on the result of the ELISA, 6 horses
      were experimentally inoculated three times intramuscularly or intranasally with
      inactivated EHV-1 vaccine. Sera collected from these horses were used to the type
      specific ELISA and complement-fixation (CF) test. Although the CF test detected a
      significant increase of antibody elicited by vaccination, the ELISA did not
      detect any antibody response. Next, sera collected from thirty-eight horses,
      which were intramuscularly inoculated with inactivated EHV-1 twice at an interval
      of four weeks, were used in the ELISA and CF test. The results also indicated
      that CF titers increased by vaccine inoculation, but ELISA titers did not. To
      examine epizootiology of EHVs serologically in racehorse populations at two
      Training Centers of the Japan Racing Association, the type-specific ELISA and CF
      test were carried out using paired sera collected from racehorses before and
      after the winter season. The results showed that the ELISA could distinguish EHV
      1 and EHV-4 infections in vaccinated horses serologically. In conclusion, the
      type-specific ELISA is considered to be useful for sero-diagnosis and sero
      epizootiological research on EHV-1 and EHV-4 infections not only in unvaccinated
      horses, but also in vaccinated horses in Japan.

PMID- 10945285
TI  - Effect of taurine in rat milk on the growth of offspring.
AB  - The physiological significance of taurine in milk in the growth of rat pups was
      investigated. Our results confirmed that taurine was at an exceptionally high
      concentration in rat milk during the lactational period, especially for the first
      few days after birth. Pups taking no milk from natural dams but from foster
      mothers at an advanced lactational period showed a slower growth rate.
      Intraperitoneal administration of taurine to the foster mothers in the first five
      days restored this growth retardation. On the other hand, intraperitoneal
      administration of beta-alanine, a transport antagonist of taurine, to the natural
      dams through the lactational period induced a slower growth rate of pups. This
      beta-alanine treatment to dams increased beta-alanine concentration, but did not
      decrease taurine concentrations in milk, and serum taurine concentration in the
      pups receiving this milk was elevated. Direct administration of beta-alanine to
      pups also increased the serum taurine concentrations dose-dependently. Beta
      alanine administration to pups significantly decreased [3H]taurine incorporation
      into all the organs examined, and in contrast. [3H]taurine concentrations in
      serum and urine were elevated. Thus, beta-alanine inhibited taurine incorporation
      into cells and accelerated taurine excretion into either urine or milk. Serum IGF
      I levels in pups receiving beta-alanine either directly or via their mothers was
      significantly lower than those in control pups. Cumulatively, taurine ingestion
      from milk at an early lactational period seems critical for normal growth of rat
      neonates due to its role in maintaining normal serum IGF-I levels.

PMID- 10945286
TI  - Expressions of vascular endothelial growth factor and basic fibroblast growth
      factor in tumors induced by two different cloned cell lines established from
      transplantable rat malignant fibrous histiocytoma.
AB  - In order to establish base-line data on angiogenic factors in development of
      mesenchymal tumors, expressions of vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) in implanted MT-8 and MT-9 tumors, both
      derived from a transplantable malignant fibrous histiocytoma (MFH) in the F344
      rat, were investigated by immunohistochemistry and Western blotting method. MT-8
      and MT-9 tumors were developed in syngeneic rats by implant of a tumor tissue
      fragment. MT-8 tumors were examined on post-implantation (PI) days 3, 6, 9 and
      17, and MT-9 tumors were on PI days 9, 14, 17 and 23. The growth of MT-8 tumors
      was faster than that of MT-9 tumors. Histologically, MT-8 tumors were features of
      undifferentiated sarcomas, whereas MT-9 tumors exhibited a typical storiform
      growth pattern of MFH. Immunohistochemically, all cells constituting MT-8 and MT
      9 tumors reacted with antibodies to VEGF and bFGF, indicating production of these
      factors by mesenchymal neoplastic cells. However, there were no marked
      differences in these immunoreactions between tumors examined. Thus, the bands
      obtained in the Western blotting methods were densitometrically scanned. The
      expression levels of VEGF and bFGF gradually increased PI day 3 to 9 in MT-8
      tumors and PI day 9 to 17 in MT-9 tumors. On last examination day, the levels of
      bFGF in both tumors and of VEGF in MT-9 tumors decreased, but the VEGF expression
      level in MT-8 tumors was still increased. These findings indicated that VEGF and
      bFGF may contribute cooperatively to angiogenesis in an early growth of
      mesenchymal tumor development.

PMID- 10945287
TI  - Role of nitric oxide in regulating the ductus arteriosus caliber in fetal rats.
AB  - The role of nitric oxide (NO) on the ductus arteriosus (DA) patency was examined
      in fetal rats at various stages of gestation. N(G)-nitro-L-arginine methyl ester
      (L-NAME, 50 mg/kg, i.p.), an NO synthase (NOS) inhibitor, or indomethacin (3
      mg/kg, p.o.), a cyclooxygenase inhibitor, was administered at 3 hr before
      cesarean section to pregnant rats ranging from day 17 to day 21 of gestation.
      Dams were decapitated and the fetuses were obtained by cesarean section. The
      fetuses were rapidly frozen in an acetone-dry ice mixture. Using rapid-freezing
      and shaving methods, the calibers of the DA and pulmonary artery were measured.
      The constrictive effect of L-NAME on the fetal DA caliber was stronger than that
      of indomethacin in 19-day-old and immature fetuses. In near-term fetuses, the
      constrictive effects of L-NAME were reduced, while indomethacin caused marked DA
      constriction. We conclude that endogenous NO may play a major role in regulating
      the patency of the DA in earlier fetal stages, while dilator prostaglandins may
      play a greater role in regulating the ductal patency in the near-term fetus.

PMID- 10945288
TI  - Safe and efficacious dosage of flecainide acetate for treating equine atrial
      fibrillation.
AB  - To determine a safe and efficacious dose of flecainide acetate for treating
      equine atrial fibrillation (Af), the safe dosage level was determined by
      injecting 1, 2, or 3 mg/kg i.v. of 1% flecainide acetate solution at a rate of
      0.2 mg/kg/min to five clinically healthy horses. Clinical signs and the ECG were
      monitored (HR, PR, QRS, and QT intervals) and blood was taken to measure the
      plasma flecainide concentration pre- and post-administration. No abnormal signs
      were observed in the 1- or 2-mg/kg groups, while agitation was observed in three
      of five horses in the 3-mg/kg group. The QRS, and QT intervals for the 3-mg/kg
      group increased significantly. The peak plasma flecainide concentrations were
      1.316 +/- 358 (SD) ng/ml, 1,904 +/- 314 ng/ml, and 2,251 +/- 387 ng/ml for the 1
      , 2-, and 3-mg/kg groups, respectively. To evaluate the efficacy of flecainide,
      Af was induced by right atrial pacing in six clinically healthy horses, and 1%
      flecainide acetate solution was then administered until they converted to sinus
      rhythm. All horses with induced Af converted. For the conversion, a total dose of
      1.40 +/- 0.63 mg/kg flecainide was required, the duration of administration was
      7.00 +/- 3.15 min and plasma flecainide concentration at conversion was 1,303 +/-
      566 ng/ml. In conclusion, flecainide acetate is a safe and effective
      antiarrhythmic agent for equine Af, and the clinically effective dosage is 1 to 2
      mg/kg.

PMID- 10945289
TI  - Immunization with recombinant surface antigens p26 with Freund's adjuvants
      against Babesia rodhaini infection.
AB  - The surface proteins of Babesia rodhaini have previously been shown to induce a
      high degree of protective immunity. In the present study, one of those proteins,
      B. rodhaini antigen p26 was expressed in Escherichia coli and in insect cells
      infected with a recombinant baculovirus. These proteins were recognized by immune
      serum from a drug-cured BALB/c mouse. While BALB/c mice immunized with both
      recombinant antigens and Freund's adjuvants showed 40-100% survival rate against
      challenge infection with B. rodhaini, saponin failed to induce protection,
      although significant levels of B. rodhaini-specific antibodies were produced in
      both immunized mice (1:1,000-2,000 by indirect immunofluorescent antibody test).
      The immunization of IFN-gamma-deficient mice with the recombinant proteins was
      not protective against B. rodhaini infection, indicating that IFN-gamma is one of
      the important factors for the survival against lethal B. rodhaini infection.

PMID- 10945290
TI  - Association of tightly spiraled bacterial infection and gastritis in pigs.
AB  - Tightly spiral bacteria were observed only in the pyloric mucosa of 4 (8.0%) of
      50 swine stomachs, mainly in the surface of epithelia, the gastric pits and the
      lumen of gastric glands. The presence of the spiral bacteria was significantly
      associated with chronic pyloric gastritis (p<0.05). Mean gastritis score of the
      bacteria-positive pyloric mucosa was 3.25 +/- 0.25, whereas that of the bacteria
      negative pyloric mucosa was 2.37 +/- 0.12. Parakeratosis and hyperkeratosis were
      spontaneously seen in the mucosa layer of pars oesophagea, regardless of the
      bacterial infection. Marked infiltration of mononuclear cells and granulocytes
      were seen in the cardiac mucosa, regardless of the bacterial infection. Mean
      gastritis score of the bacteria-positive cardiac mucosa was 3.27 +/- 0.32,
      whereas that of the bacteria-negative cardiac mucosa was 2.84 +/- 0.13. There was
      no significant difference between the bacteria-positive and negative cardiac
      mucosa (p>0.05). Inflammatory response in the fundic mucosa was rare (gastritis
      score=0.75 +/- 0.08). The tightly spiraled bactera were not cultured with various
      culture media. These results suggest that the presence of tightly spiraled
      bacteria is associated with only the pyloric gastritis in pigs.

PMID- 10945291
TI  - A role of pituitary adenylate cyclase activating polypeptide (PACAP) as a
      regulator of paracrine interactions between folliculo-stellate cells and
      gonadotropes through the control of activin-follistatin interactions.
AB  - Pituitary folliculo-stellate (FS) cells were able to modify the effect of activin
      A on gonadotropes through the paracrine factor, follistatin. The present study
      was aimed to examine whether a hypothalamic peptide, pituitary adenylate cyclase
      activating polypeptide (PACAP), could be a regulator of this paracrine
      interaction. Co-culture of FS cell-originated cell line TtT/GF cells with rat
      anterior pituitary cells showed faint inhibitory effect on the stimulatory action
      of activin-A on FSH secretion. When PACAP was added to the culture during the co
      culture period, however, the presence of TtT/GF cells caused significant
      suppression of the effect of activin-A on FSH secretion. Conditioned-media (CM)
      from TtT/GF cells, obtained by incubation of TtT/GF cells in the presence or
      absence of PACAP, were next added to the cultures of anterior pituitary cells
      alone. CM from TtT/GF cells without PACAP treatment revealed slight, but not
      significant, suppressive effect on activin-induced increases in FSH secretion and
      the percentage of FSH cells. Meanwhile, CM from PACAP-treated TtT/GF cells
      attenuated both effects of activin-A. Furthermore, the inhibitory effect of the
      CM was neutralized when follistatin antibody was present in the culture. These
      results suggest that PACAP is able to regulate the paracrine action of FS cells
      on pituitary gonadotropes. Besides expressing direct actions on pituitary
      endocrine cells, PACAP may have roles as a regulator of cell-to-cell interactions
      within the pituitary gland.

PMID- 10945292
TI  - The cause of the predilection of Babesia gibsoni for reticulocytes.
AB  - This study was conducted to determine why Babesia gibsoni replicates well in
      reticulocytes. First, B. gibsoni was cultivated in resealed erythrocyte ghosts
      loaded with either erythrocyte or reticulocyte lysate, and in reticulocyte ghosts
      loaded with either erythrocyte or reticulocyte lysate. The parasites multiplied
      well in the erythrocyte or reticulocyte ghosts loaded with reticulocyte lysate
      compared to the other resealed cells loaded with erythrocyte lysate. Second, the
      parasites were cultivated in erythrocytes in culture medium supplemented with
      either erythrocyte or reticulocyte lysate. The parasites multiplied better in
      reticulocyte lysate-containing cultures than in erythrocyte lysate-containing
      cultures. Finally, the parasites were cultivated in erythrocytes in culture
      medium supplemented with glutamate, aspartate, asparagine, glycine, isoleucine,
      proline, taurine or GSH, which were present in higher concentrations in
      reticulocytes than in erythrocytes. Supplementation of the culture medium with
      glutamate and GSH resulted in enhancement of the multiplication of the parasites,
      while the other amino acids did not enhance the multiplication. These results
      indicated that the high levels of the multiplication of B. gibsoni in
      reticulocytes are partly due to the high concentrations of glutamate and GSH in
      reticulocytes.

PMID- 10945293
TI  - Immunohistochemical analysis of cyclin A, cyclin D1 and P53 in mammary tumors,
      squamous cell carcinomas and basal cell tumors of dogs and cats.
AB  - The involvement of cyclin A, cyclin D1 and p53 proteins in canine and feline
      tumorigenesis was analyzed immunohistochemically. In the present study, a total
      of 176 cases were examined, among which there were 108 canine cases (75 mammary
      lesions, 16 squamous cell carcinomas and 17 basal cell tumors) and 68 feline
      cases (43 mammary lesions, 20 squamous cell carcinomas and 5 basal cell tumors).
      Speckled nuclear staining for cyclin A was observed in 19/38 (50%) canine
      malignant mammary tumors and 18/37 (48.6%) feline mammary carcinomas, while this
      was not seen in benign mammary tumors of either dogs or cats. Marked intense
      nuclear cyclin A staining was seen in 7/16 (43.8%) canine squamous cell
      carcinomas and 18/20 (90.0%) feline squamous cell carcinomas. Only 3/17 (17.6%)
      canine basal cell tumors showed slight and scattered staining for cyclin A.
      Expression of cyclin D1 was very rare in both canine and feline tumors. Nuclear
      staining of p53 was found in 7/37 (18.9%) feline mammary carcinomas. Intense
      immunoreactivity for p53 was found in 6/16 (37.5%) canine squamous cell
      carcinomas and 8/20 (40%) feline squamous cell carcinomas. These results suggest
      that cyclin A may have a role in the proliferation of canine malignant mammary
      tumors, feline mammary carcinomas and squamous cell carcinomas of dogs and cats,
      and p53 may associate with the tumorigenesis of feline mammary carcinomas and
      squamous cell carcinomas of dogs and cats.

PMID- 10945295
TI  - Ultrasonographic findings of an ovarian abscess in a cow.
AB  - Ultrasonographic examination was carried out in a cow with an ovarian abscess.
      Real time ultrasound scanning using a 7.5 MHz linear probe per rectum revealed an
      active left ovary with follicles of up to 11 mm in diameter and an enlarged right
      ovary measuring 6 x 6 cm, with a mass of 4 x 3 cm. The mass had varied
      echotexture, a thick hyperechoic boundary and a hypoechoic centre with echoic
      foci. It was tentatively diagnosed as an ovarian tumour or abscess. After
      ovariectomy, grossly the right ovary measured 6 x 6 x 5 cm and on cutting cheesy
      pus oozed out. The abscess was completely localised within the ovary, 4 cm in
      diameter and encapsulated thickly. On bacteriological examination Staphylococcus
      spp. was isolated. This is a rare case of ovarian abscess.

PMID- 10945294
TI  - Sequential observation of 2,6-dimethylaniline-induced nasal lesions in a rat two
      stage nasal carcinogenesis model after initiation with N-bis(2-hydroxypropyl)
      nitrosamine.
AB  - Male F344 rats received diet containing 3,000 ppm 2,6-dimethylaniline (DMA) after
      initiation with a single subcutaneous injection of 2,400 mg/kg of N-bis(2
      hydroxypropyl)nitrosamine (DHPN), and histological and electron microscopic
      examinations of the nasal cavity were performed at 4, 13, 26 and 52 weeks to
      examine sequential changes induced by DMA. Severe atrophy of Bowman's glands and
      epithelial disarrangement were apparent from week 4, followed by dilatation
      and/or proliferation of Bowman's glands, degeneration of epithelial cells, and
      proliferation of undifferentiated epithelial cells from week 13. Focal glandular
      hyperplasias, dysplastic foci, and adenomas were observed from week 26, and
      carcinomas at 52 week. These nasal lesions were mostly evident in the olfactory
      mucosa in the nasal cavity, and their severity and/or incidences, other than
      atrophy of Bowman's glands, increased with the treatment period. Electron
      microscopically, carcinoma cells demonstrated desmosomes, dense secretory
      granules identical to those in normal Bowman's glands, a basement membrane, and
      microvilli. These results suggest that Bowman's glands are the target of DMA,
      giving rise to nasal carcinomas after DHPN-initiation.

PMID- 10945296
TI  - Sympatric distribution of the two morphological types of the common tree shrew in
      Hat-Yai districts (South Thailand).
AB  - The two color types (grayish northern and reddish southern types) of the common
      tree shrew (Tupaia glis and Tupaia belangeri) were co-distributed in Hat-Yai
      region (South Thailand). Although the Isthmus of Kra in South Thailand has been
      considered as distribution barrier of the two types, the sympatric distribution
      of both types was confirmed in southern side of the Isthmus. In the principal
      component analysis, the skull measurement character from Hat-Yai region could
      also be separated into the northern and southern groups according to the skin
      color identification of corresponding individuals. We could generally distinguish
      the common tree shrew into two types by skull morphology as well as external skin
      color.

PMID- 10945297
TI  - Induction of unseasonable hibernation and involvement of serotonin in entrance
      into and maintenance of its hibernation of chipmunks T. asiaticus.
AB  - Chipmunks that had been housed at 22 degrees C under a light-dark cycle of
      14L:10D for at least one year were exposed to a short photoperiod (10L:14D) and
      low temperature to induce unseasonable hibernation. We were able to induce
      hibernation at any time of year and there was no significant difference in the
      duration of the hibernation bout, the duration of interbout euthermia and
      duration of bouts of torpor throughout the year; however entrance into
      hibernation took about 60 days in summer but only about 30 days in any other
      seasons. In addition, interbout euthermia predominantly occurred during the light
      phase in winter, whereas in spring interbout euthermia occurred equally in the
      light and dark phases. These results suggest that both the circadian and
      circannual systems are linked to hibernation in chipmunks. Subcutaneous infusion
      of a serotonin antagonist, para-chlorophenylalanine (PCPA), facilitated entrance
      into and interrupted hibernation in aroused and hibernating chipmunks in summer,
      respectively. On the other hand, opioid antagonist, naloxone, did not affect
      hibernation, but extended the period of interbout euthermia. These results
      suggest that the role of serotonin in entrance into and maintenance of
      hibernation in chipmunks is independent of the circannual system, and that opioid
      system may not be involved in hibernation in chipmunks.

PMID- 10945298
TI  - Salmonella virchow infection in an infant transmitted by household dogs.
AB  - A 4-month-old male infant manifested diarrhea and Salmonella Virchow was isolated
      from his stool. The pathogen was repeatedly isolated from the infant over one
      month despite three regimens of treatment with antibiotics, to which the isolate
      was sensitive. Three household dogs were kept in his home and S. Virchow was
      isolated from two of them. The infant was admitted to hospital and was treated
      with antibiotic, then the pathogen was finally eliminated. Antibiotic sensitivity
      pattern and PFGE pattern produced by restriction enzyme Xba I of the isolate from
      the infant was completely similar to those of the isolates from the dogs. The
      above findings indicated that the present S. Virchow infection in the infant was
      transmitted by the household dogs.

PMID- 10945299
TI  - Immunohistochemistry and polymerase chain reaction for the detection of Lawsonia
      intracellularis in porcine intestinal tissues with proliferative enteropathy.
AB  - Detection method of Lawsonia intracellularis was studied in formalin-fixed
      paraffin-embedded intestinal tissues from 5 naturally infected pigs by
      immunohistochemistry with a monoclonal antibody against outer membrane protein of
      L. intracellularis. Warthin-Starry silver stain revealed clusters of
      argyrophilic, slightly curved rod-shaped organisms in the apical cytoplasm of
      enterocytes. Immunohistochemical staining with a L. intracellularis-specific
      monoclonal antibody confirmed the presence of the organism in the apical
      cytoplasm of hyperplastic enterocytes. The presence of L. intracellularis in the
      ileum of pig with proliferative enteropathy was confirmed by polymerase chain
      reaction (PCR) further on the basis of amplification of 319 base pair products
      specific for porcine L. intracellularis chromosomal DNA. Immunohistochemistry and
      PCR may be a complementary method to confirm the diagnosis of L. intracellularis
      infection in pigs.

PMID- 10945300
TI  - Antibodies to Borna disease virus in infected adult rats: an early appearance of
      anti-p10 antibody and recognition of novel virus-specific proteins in infected
      animal brain cells.
AB  - The time course for appearance of antibodies to Borna disease virus (BDV) major
      antigens, p40, p24, p18 and p10 were investigated in BDV-inoculated adult rats by
      Western blotting. Anti-p10 antibodies were detected in sera as early as anti-p40
      and -p24 antibodies at four or five weeks after inoculation. Furthermore, in
      addition to these major antigens of BDV, the rat serum could detect additional 80
      , 58-, 43-, 20-, and 16-kDa proteins in BDV-infected cultured cells and/or animal
      brain cells by Western blot analysis. Of these proteins, the 20- and 16-kDa
      proteins were shown to be related to p24 protein by their reactivity with anti
      p24 monoclonal antibody. Interestingly, the 58- and 24-kDa were found only in BDV
      infected animal brain cells but not in cultured cells. The results in this study
      could provide a useful information on the mechanism for the viral replication and
      pathogenesis.

PMID- 10945301
TI  - Seroprevalence of bovine immunodeficiency virus and bovine leukemia virus in
      draught animals in Cambodia.
AB  - Since bovine immunodeficiency virus (BIV), known as bovine lentivirus, has been
      detected in dairy and beef cattle in various countries around the world, a
      prevalence study of antibodies to BIV and bovine leukemia virus (BLV) was
      conducted in draught animals in five provinces in Cambodia, where protozoan
      parasite infections were suspected in some animals. To clarify the status of
      draught animals including Haryana, Brahman, mixed-breed, local breed cattle and
      muscle water buffaloes, a total of 544 cattle and 42 buffaloes were tested, and
      26.3 and 16.7%, respectively, were found positive for anti-BIV p26 antibodies
      determined by Western blotting. There were 5.3% positive for anti-BLV antibodies
      detected by immunodiffusion test among the cattle, but no reactors among
      buffaloes and no dual infection for both BIV and BLV was determined in this
      study. Peripheral blood mononuclear cells from BIV-seropositive cattle were found
      to have BIV-provirus DNA, as detected by polymerase chain reaction and subsequent
      Southern blot hybridization. This is the first evidence for the presence of BIV
      and BLV infections in draught animals in tropical countries such as Cambodia.
      This wide distribution of BIV suggests its association with problems in animal
      health as reported worldwide, and that a primary BIV infection can predispose
      death of affected animals by other aggressive pathogens or stresses.

PMID- 10945302
TI  - Amplification of the cyclin A gene in canine and feline mammary tumors.
AB  - DNAs from 33 canine mammary tumors and 8 feline mammary carcinomas were examined
      by Southern blot analysis to clarify genomic abnormalities of the cyclin A gene.
      Amplification of cyclin A was detected in 27.3% (9/33) of canine mammary tumors
      and 87.5% (7/8) of feline mammary carcinomas. It was suggested that amplification
      of cyclin A do not correlate directly with the tumorigenesis of canine mammary
      tumors, because there was no significant difference of incidence of cyclin A
      amplification between the benign and malignant tumors. In feline mammary
      carcinomas, the high frequency of cyclin A amplification raised the possibility
      that the amplification lead to the protein overexpression and play an important
      role in the tumorigenesis.

PMID- 10945303
TI  - Salmonella contamination in commercial layer feed in Japan.
AB  - A total of 4,418 samples of commercial layer feeds obtained in 1998 were
      investigated for the presence of salmonellae. A total of 146 strains of
      salmonellae which consisted of 32 serovars, including 20 strains of Salmonella
      Enteritidis, were isolated from 143 feed samples.

PMID- 10945304
TI  - Ovarian and retroperitoneal teratomas in a dog.
AB  - A 2-year-old female Labrador retriever was presented with anorexia and abdominal
      distention. Laparotomy revealed the presence of a 31-cm ovoid mass in the portion
      of the left ovary and an 11-cm round mass in the left retroperitoneal region.
      Both masses were surgically removed. Histopathological examination of the masses
      revealed a mixture of tissues characteristic of teratomas, such as multiple
      bronchial and intestinal cysts, hair follicles, sebaceous and apocrine sweat
      glands, and neuron tissue with intervening cartilage, bone and fat tissue. This
      paper appears to be the first report of primary retroperitoneal teratoma in the
      dog.

PMID- 10945305
TI  - Sequence of 16S rRNA gene of rat-origin cilia-associated respiratory (CAR)
      bacillus SMR strain.
AB  - The 16S rRNA gene of the SMR strain of cilia-associated respiratory (CAR)
      bacillus, which was isolated from a spontaneously infected rat at our institute,
      was sequenced. Its 1,521 nucleotides were determined. On the basis of the results
      of the sequence analysis, the SMR strain was found to be most closely related to
      members of the Flavobacter/Flexibacter group. This sequence was compared with the
      previously determined 16S rRNA gene sequences (rat-origin: three; mouse-origin:
      one; rabbit-origin: one) of CAR bacillus isolates. The SMR strain showed the
      highest sequence similarity (99.9%) to the rat-origin CARB-NIH strain (Schoeb et
      al., 1993), and it was concluded that the strains are identical.

PMID- 10945306
TI  - Recent epidemiological status of feline upper respiratory infections in Japan.
AB  - Epidemiology of upper respiratory infections of cats was studied. Nasal, ocular,
      and oral swabs collected from 111 cats presented at animal hospitals during the
      past 2.5 years were examined. Twenty-four (21.6%) and 4 (3.6%) cats were
      diagnosed as feline calicivirus (FCV) infection and feline viral rhinotracheitis,
      respectively, indicating FCV is more prevalent than feline herpesvirus-1, which
      revealed a considerable shift from data obtained in 1970s. Cat sera immunized by
      using vaccines containing either FCV F9 or 255 strains neutralized 42.9% and
      66.7% of the FCV isolates, respectively. Chlamydia psittaci, examined by a PCR
      assay amplifying the ompA gene, was found in 26.9% of 26 diseased cats that
      typically showed conjunctivitis and rhinitis.

PMID- 10945307
TI  - Application of latex beads agglutination test for the detection of the antibody
      against virus-infection-associated (VIA) antigen of foot-and-mouth disease (FMD)
      virus.
AB  - Latex beads agglutination (LA) for the detection of the antibody against virus
      infection-associated (VIA) antigen of foot-and-mouth disease (FMD) virus was
      estimated using experimentally infected animals. The VIA antibody titer by the LA
      test were compared with the neutralization titer and the titer by agarose gel
      diffusion (AGD) test, which has been used as a standard method for VIA antibody
      titration. The latex beads were coated with VIA antigen in carbonate buffer
      solution (0.5 M, pH 9.6) for the test. The sensitivity of the LA test was clearly
      higher than that of the AGD test in the results for cattle and swine infected
      experimentally. The antibody was detected in the bovine serum obtained at the
      13th week after inoculation by the LA but not by the AGD test. The LA test
      appears to be simple, rapid and sensitive for the detection of the antibody of
      FMD virus in the surveillance of FMD and the FMD quarantine of imported animals.

PMID- 10945308
TI  - Is it sex or is it gender?

PMID- 10945309
TI  - Targeting oral anticoagulation.

PMID- 10945310
TI  - Oral bioavailability of digoxin is enhanced by talinolol: evidence for
      involvement of intestinal P-glycoprotein.
AB  - OBJECTIVE: Recent data indicated that disposition of oral digoxin is modulated by
      intestinal P-glycoprotein. The cardioselective beta-blocker talinolol has been
      described to be secreted by way of P-glycoprotein into the lumen of the
      gastrointestinal tract after oral and intravenous administration. We therefore
      hypothesized that coadministration of digoxin and talinolol may lead to a drug
      drug interaction based on a competition for intestinal P-glycoprotein. METHODS:
      Pharmacokinetics of digoxin (0.5 mg orally), talinolol (30 mg intravenously and
      100 mg orally), and digoxin plus talinolol orally, as well as digoxin plus
      talinolol intravenously, were assessed in five male and five female healthy
      volunteers (age range, 23 to 30 years; body weight, 60 to 95 kg) in a changeover
      study with at least a 7-day washout period. Digoxin and talinolol were analyzed
      by fluorescence polarization immunoassay and HPLC, respectively. RESULTS: Oral
      coadministration of 100 mg talinolol increased the area under the concentration
      time curve (AUC) from 0 to 6 hours and the AUC from 0 to 72 hours of digoxin
      significantly by 18% and 23%, respectively (5.85+/-1.49 versus 7.22+/-1.29 ng x
      h/mL and 23.0+/-3.3 versus 27.1+/-3.7 ng x h/mL, for both P<.05) and the maximum
      serum levels by 45%. Renal clearance and half-life of digoxin remained unchanged.
      Coinfusion of 30 mg talinolol with oral digoxin had no significant effects on
      digoxin pharmacokinetics. Digoxin did not affect the disposition of talinolol
      after both oral and intravenous administration. CONCLUSION: We observed a
      significantly increased bioavailability of digoxin with oral coadministration of
      talinolol, which is most likely caused by competition for intestinal P
      glycoprotein.

PMID- 10945311
TI  - Reduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics
      by separation of their time of administration.
AB  - BACKGROUND: Budesonide is a glucocorticosteroid used in the treatment of, for
      example, inflammatory bowel diseases, with a recommended once-daily morning
      dosing regimen. Ketoconazole is a potent inhibitor of the cytochrome P450 3A
      (CYP3A) activities and known to inhibit the elimination of drugs metabolized by
      CYP3A, including budesonide. It is of therapeutic interest to know whether the
      influence of ketoconazole can be reduced by administration on an occasion
      different in time to CYP3A substrates. METHODS: Eight healthy men completed this
      randomized, open crossover study that comprised three different periods. In
      period 1, a single oral dose of 3 mg budesonide was given in the morning. In
      period 2, a 200-mg ketoconazole tablet was administered once daily in the morning
      on 4 consecutive days. On the fourth day, 3 mg budesonide was administered at the
      same time as the ketoconazole. In period 3, 200 mg ketoconazole was administered
      once daily in the evening on 4 consecutive days. On the fourth day, 3 mg
      budesonide was administered 12 hours before the ketoconazole. One-week washout
      periods separated the budesonide administrations. RESULTS: The mean area under
      the plasma drug concentration-time curve [AUC(0-24)] for budesonide was increased
      by 6.5 times when it was given simultaneously with ketoconazole. When the
      administrations of the two drugs were separated by 12 hours, the mean AUC(0-24)
      for budesonide was increased by only 3.8 times. CONCLUSION: This study shows that
      the capability of ketoconazole to inhibit the elimination of budesonide is
      significantly reduced (by 50%) by a 12-hour separation of the administration
      times.

PMID- 10945312
TI  - Comparison of manual versus ambulatory blood pressure measurements with
      pharmacokinetic-pharmacodynamic modeling of antihypertensive compounds:
      application to moxonidine.
AB  - OBJECTIVES: To compare the results of the pharmacokinetic-pharmacodynamic
      analyses of 24-hour ambulatory blood pressure measurements and manual blood
      pressure data in patients receiving moxonidine. METHODS: 32 patients with
      borderline to mild-to-moderate hypertension were enrolled in a double-blind,
      placebo-controlled phase II study. After receiving placebo for 1 week (run-in
      phase), the patients were randomly allocated to the placebo or the 0.6-, 0.9-, or
      1.2-mg dose groups. Placebo and moxonidine were administered once daily for 1
      week (drug-treatment phase). Four 24-hour ambulatory blood pressure measurement
      profiles were obtained for each individual. Plasma samples (n = 9) and four
      measurements of manual blood pressure were taken at the start and end of the drug
      treatment phase. Two additional manual blood pressure measurements were taken
      during the run-in and drug-treatment phases. RESULTS: Pharmacokinetics was
      described by a one-compartment model. For the 24-hour ambulatory blood pressure
      measurements, baseline circadian patterns were described with a two-cosine
      function model that included interindividual and interoccasion variability.
      Pharmacodynamics was described with use of an effect-compartment model [k(e0) =
      0.37 (1/h)] and an Emax model. For diastolic blood pressure the maximum drug
      induced decrease (Emax) was 30.9 mm Hg and the steady-state plasma drug
      concentration eliciting half of maximum effect (C50) was 1.33 microg/L.
      Interindividual variability was estimated for ke0 (24.8%) and Emax (33.3%). For
      the manual blood pressure measurements, data was described by a time-invariant
      baseline model combined with an effect-compartment model and an Emax model. Mean
      population estimates were in agreement with those obtained during the analysis of
      24-hour ambulatory blood pressure measurements. However, interindividual
      variability could be estimated for the baseline parameter only. CONCLUSIONS:
      Although similar typical population estimates for the drug action-related
      parameters were obtained with use of manual blood pressure data and 24-hour
      ambulatory blood pressure measurements, the latter allowed for a more detailed
      description of the individual pharmacodynamic profiles because interindividual
      variability in pharmacodynamic parameters could be estimated together with
      increased precision in parameter estimates.

PMID- 10945313
TI  - Grapefruit juice--felodipine interaction in the elderly.
AB  - BACKGROUND: Grapefruit juice can increase the oral bioavailability of a broad
      range of medications. This interaction has not been assessed in the elderly.
      METHODS: Twelve healthy elderly people (70 to 83 years of age) were administered
      5 mg felodipine extended release with 250 mL grapefruit juice or water in a
      single-dose study. Subsequently, 6 of these people received 2.5 mg felodipine for
      2 days, followed by 5 mg felodipine for 6 days with 250 mL grapefruit juice or
      water in a steady-state study. Plasma concentrations of felodipine and
      dehydrofelodipine metabolite, blood pressure, and heart rate were measured over
      24 hours after single and final steady-state dose. RESULTS: Mean felodipine area
      under the curve and maximum concentration were 2.9-fold and 4.0-fold greater,
      respectively, with grapefruit juice in both studies. Interindividual variability
      in the extent of the interaction was high. Felodipine apparent elimination half
      life was not altered. Dehydrofelodipine area under the curve and maximum
      concentration were increased and dehydrofelodipine/felodipine area under the
      curve ratio was reduced. Systolic and diastolic blood pressures were lower with
      grapefruit juice in the single-dose study, whereas they were not different
      between treatments in the steady-state study. Curvilinear relationships existed
      between plasma felodipine concentration and changes in systolic and diastolic
      blood pressures. Heart rates were higher with grapefruit juice in both studies;
      however, this effect was greater and more prolonged at steady state. CONCLUSIONS:
      A normal dietary amount of grapefruit juice produced a pronounced, unpredictable,
      and sustained pharmacokinetic interaction with felodipine by reducing its
      presystemic metabolism in the elderly. The different blood pressure results
      between the studies can be explained by felodipine concentration-blood pressure
      response relationships. The elderly should be particularly cautioned about
      concomitant grapefruit juice and felodipine ingestion.

PMID- 10945315
TI  - Pharmacokinetic and pharmacodynamic interaction between mexiletine and
      propafenone in human beings.
AB  - BACKGROUND AND OBJECTIVE: Mexiletine and propafenone are often used concomitantly
      and are metabolized by the same cytochrome P450 isozymes, namely CYP2D6, CYP1A2,
      and probably CYP3A4. Our objective was to study the potential pharmacokinetic and
      electrophysiological interactions between mexiletine and propafenone. METHODS:
      Fifteen healthy volunteers, 8 extensive metabolizers and 7 poor metabolizers of
      CYP2D6, received oral doses of mexiletine 100 mg two times daily from day 1 to
      day 8 and oral doses of propafenone 150 mg two times daily from day 5 to day 12.
      Interdose studies were performed at steady-state on mexiletine alone (day 4),
      mexiletine plus propafenone (day 8), and propafenone alone (day 12). RESULTS: In
      subjects in the extensive metabolizer group, coadministration of propafenone
      decreased oral clearances of R-(-)-mexiletine (from 41+/-11 L/h to 28+/-7 L/h)
      and S-(+)-mexiletine (from 43+/-15 L/h to 29+/-11 L/h) to an extent such that
      these values were no longer different between the extensive and the poor
      metabolizer groups. Propafenone coadministration also decreased partial metabolic
      clearances of mexiletine to hydroxymethylmexiletine, p-hydroxymexiletine, and m
      hydroxymexiletine in extensive metabolizers by 71%, 67%, and 73%, respectively.
      In contrast, propafenone did not alter the kinetics of mexiletine enantiomers in
      subjects in the poor metabolizer group except for a slight decrease in the
      formation of hydroxymethylmexiletine. Pharmacokinetic parameters of propafenone
      were not changed during concomitant administration of mexiletine in subjects of
      either phenotype. Finally, electrocardiographic parameters (QRS duration, QTc,
      RR, and PR intervals) were not modified during the combined administration of the
      drugs. CONCLUSION: Propafenone is a potent CYP2D6 inhibitor that may cause an
      increase in plasma concentrations of coadministered CYP2D6 substrates.

PMID- 10945314
TI  - Inhibition of cytochrome P450 2A6 increases nicotine's oral bioavailability and
      decreases smoking.
AB  - BACKGROUND: Nicotine establishes and maintains tobacco dependence. Individuals
      with genetically deficient CYP2A6 nicotine metabolism are at lower risk to become
      smokers and, if dependent, will smoke fewer cigarettes. Hepatic CYP2A6 accounts
      for nicotine's low systemic bioavailability, precluding oral nicotine replacement
      to treat dependence. OBJECTIVE: We sought to determine whether CYP2A6 inhibition
      via oral methoxsalen decreases nicotine clearance, increases nicotine
      bioavailability, and decreases smoking. METHODS: Two within-subject designs in
      healthy tobacco-dependent volunteers were conducted: a singleblind kinetic study
      (n = 17) of methoxsalen 30, 10, or 3.5 mg or placebo given with nicotine 4 mg
      orally to abstinent smokers; and a double-blind randomized crossover study (n =
      11) of methoxsalen 30 mg or placebo crossed with nicotine 4 mg given orally or
      placebo before 60 minutes' abstinence and 90 minutes' free smoking. RESULTS:
      Placebo plus nicotine 4 mg orally increased the mean 3-hour plasma nicotine level
      by 4 ng/mL over residual baseline nicotine level, whereas methoxsalen 10 or 30 mg
      plus nicotine increased it by 9 ng/mL (P<.01), demonstrating in vivo inhibition
      of CYP2A6 nicotine metabolism. Methoxsalen 30 mg plus nicotine 4 mg given orally
      decreased breath carbon monoxide concentration at the end of free smoking by 47%
      (4.6 versus 8.7 ppm; P<.01) and cigarettes smoked by 24% (3.1 versus 4.1, P<.01)
      compared with placebo plus placebo. CONCLUSIONS: Methoxsalen inhibits nicotine
      first-pass metabolism of orally administered nicotine, and the combination
      directly reduces smoking in a laboratory setting. CYP2A6 inhibitors may have an
      important role in smoking cessation and tobacco exposure reduction.

PMID- 10945316
TI  - Nicotine-mecamylamine interactions.
AB  - OBJECTIVES: Mecamylamine blocks nicotinic cholinergic receptors and has been
      proposed, in combination with nicotine, as a novel therapy to aid smoking
      cessation. The objective of this study was to characterize the pharmacokinetic
      and pharmacodynamic interactions between transdermal mecamylamine and intravenous
      nicotine. STUDY DESIGN: Twelve cigarette smokers were studied while receiving
      transdermal mecamylamine 6 mg/24 h and placebo patches for 7 days each. On the
      fifth day of patch use, subjects received a combined infusion of deuterium
      labeled nicotine and cotinine, with measurement of disposition kinetics of
      nicotine and cotinine, and cardiovascular and plasma catecholamine responses to
      nicotine. Half of the subjects were studied under alkaline urine conditions and
      the other half under acidic urine conditions. RESULTS: Steady-state plasma
      mecamylamine concentrations were twice as high (mean, 12.2 versus 6.3 ng/mL),
      consistent with lower renal clearance (2.1 versus 5.8 mL/min/kg) during alkaline
      compared with acidic urine conditions. Mecamylamine did not significantly affect
      the clearances of nicotine or cotinine. Mecamylamine significantly reduced the
      volume of distribution and inhibited the cardioacceleratory and epinephrine
      releasing effects of nicotine. CONCLUSIONS: Mecamylamine has little effect on the
      clearance of nicotine and is not expected to affect steady-state levels during
      transdermal nicotine dosing. The reduction of the volume of distribution of
      nicotine by mecamylamine suggests that part of the antagonism of nicotinic
      central nervous system effects by mecamylamine may be due to a pharmacokinetic
      interaction-most likely decreased transport of nicotine into the brain or
      decreased binding to nicotine receptors. Mecamylamine may decrease the potential
      adverse cardiovascular effects of coadministered nicotine.

PMID- 10945317
TI  - Big endothelin-3 constricts forearm resistance vessels but not hand veins in
      humans.
AB  - BACKGROUND: Endothelin-3 (ET-3) and its inactive precursor, big endothelin-3 (big
      ET-3), are both found in human plasma. We investigated whether big ET-3 is
      converted to ET-3 in the human forearm resistance vessels and dorsal hand veins
      in vivo. METHODS: In a 4-phase study, 6 subjects received 90 minute intrabrachial
      artery infusions of big ET-3 (50 and 100 pmol x min(-1)) and ET-3 (5 and 10 pmol
      x min(-1)) in random order. Forearm blood flow was measured by venous occlusion
      plethysmography. In a second 3-phase study, 6 subjects received 90-minute dorsal
      hand vein infusions of saline solution, big ET-3 (50 pmol x min(-1)) and ET-3 (5
      pmol x min(-1)) in random order. In a third 2-phase study, 6 subjects received 90
      minute dorsal hand vein infusions of big ET-3 (100 pmol x min(-1)) and ET-3 (10
      pmol x min(-1)). In the dorsal hand vein studies, vessel diameter was measured by
      the Aellig technique. RESULTS: Intra-arterial ET-3 caused local forearm
      vasoconstriction of 20%+/-9% (P = .009) at 5 pmol x min(-1) and 20%+/-10% (P =
      .001) at 10 pmol x min(-1) after 90 minutes, with no difference between doses (P
      = .69). Intra-arterial big ET-3 also caused local forearm vasoconstriction of
      22%+/-6% at 50 pmol x min(-1) (P = .004) and 18%+/-3% at 100 pmol x min(-1)
      (P<.0001) after 90 minutes, with no difference between doses (P = .44). There
      were no significant differences between the responses to intra-arterial big ET-3
      and ET-3 at these doses. Local intravenous ET-3 caused a constriction of 9%+/-2%
      at 5 pmol x min(-1) (P = .04) and 22%+/-8% at 10 pmol x min(-1) (P = .002) after
      90 minutes. Big ET-3 at 50 pmol x min(-1) and 100 pmol x min(-1) did not affect
      hand vein tone. All responses were slowly progressive. CONCLUSIONS: Based on
      vasoconstriction, measurable conversion of big ET-3 to ET-3 occurs in forearm
      resistance vessels but not in dorsal hand veins in vivo. An endothelin-converting
      enzyme, capable of converting exogenously administered big ET-3 to ET-3, appears
      to be present in upper limb resistance arteries but not in capacitance vessels in
      humans.

PMID- 10945318
TI  - A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins
      with damaged endothelium.
AB  - BACKGROUND: Reduced nitric oxide bioavailability caused by endothelial
      dysfunction or damage is a contributory factor in the initiation and progression
      of a number of cardiovascular diseases. Delivery of exogenous nitric oxide is an
      attractive therapeutic option, but current agents lack selectivity for areas of
      endothelial damage. We tested the hypothesis that a novel nitric oxide donor
      drug, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acet yl
      P-glucopyranose [RIG200], which has selective effects in endothelium-denuded
      isolated arteries in vitro, would exert similar effects in dorsal hand veins with
      experimentally damaged endothelium in vivo. METHODS: Venodilator responses to
      sodium nitroprusside and RIG200 were compared in two groups of healthy volunteers
      (age range, 18 to 63 years; n = 7 for each group) in norepinephrine 70% maximum
      effective concentration (EC70) preconstricted hand veins with use of the Aellig
      technique. In this doubleblind study, subjects were randomly assigned to receive
      either sodium nitroprusside or RIG200 (infusions of 0.06 and 6 nmol/min into the
      hand vein) before and 2 days after 15 minutes of local venous irription with
      distilled water. Endothelial function was assessed in all subjects on both visits
      with use of the endothelium-dependent vasodilator acetylcholine (1 nmol/min).
      RESULTS: Irrigation of hand veins with distilled water abolished endothelium
      dependent dilatation in response to acetylcholine in both study groups (n = 14)
      but did not affect the amplitude or duration of responses to the conventional
      nitric oxide donor sodium nitroprusside (P = .87; n = 7). However, responses to
      RIG200 were significantly prolonged during the washout phase (30 minutes) in
      veins after water irrigation (P = .02; n = 7). CONCLUSION: These studies confirm
      that RIG200 has prolonged effects in veins with damaged endothelium, a
      characteristic that might be exploited therapeutically to target nitric oxide
      delivery to damaged blood vessels.

PMID- 10945319
TI  - CYP3A activity in African American and European American men: population
      differences and functional effect of the CYP3A4*1B5'-promoter region
      polymorphism.
AB  - OBJECTIVE: Cytochrome P4503A (CYP3A) activity exhibits considerable
      interindividual variability. Possible differences in CYP3A activity were
      investigated in European American and African American men with the use of
      midazolam as an in vivo probe. METHODS: Midazolam was simultaneously administered
      intravenously (1 mg, [15N3]-labeled) and orally (2 mg, unlabeled in capsule form)
      to 15 young healthy European American men and a similar group of men of African
      American descent. Plasma concentration-time curves were measured. The subjects
      were subsequently genotyped with respect to the CYP3A4*B1 polymorphism (A-290G)
      in the 5'-promoter (nifedipine-specific element) region. RESULTS: The oral
      bioavailability of midazolam was about equally determined by intestinal and
      hepatic extraction with CYP3A activity at the former site exhibiting greater
      variability. Oral bioavailability was related to intestinal metabolism (r =
      0.98), whereas hepatic CYP3A activity contributed little to the interindividual
      variability (r = 0.03). A lower systemic clearance (265+/-54 versus 310+/-56
      mL/min; P = .04), but not oral clearance, was observed in African Americans. With
      one exception, the African Americans possessed a variant CYP3A4*1B allele (4
      heterozygotes A/G and 10 homozygote G/G), whereas all of the European Americans
      were wild-type homozygotes (A/A). Hepatic CYP3A activity and the systemic
      clearance of midazolam were about 30% lower in G/G homozygotes than in A/A
      homozygotes (252+/-53 versus 310+/-54 mL/min; P = .02), and a gene-dose effect
      was present (P = .01). There was no genotype/phenotype relationship with respect
      to the oral clearance of midazolam. CONCLUSION: Comparison of CYP3A activity
      between populations is complicated by frequency distribution differences in the
      regulatory CYP3A4*1B polymorphism and lower hepatic CYP3A activity associated
      with the variant allele. However, this reduction is modest; therefore no major
      and clinically important difference in CYP3A activity is present between
      Americans of African or European descent.

PMID- 10945320
TI  - Quetiapine fumarate overdose: clinical and pharmacokinetic lessons from extreme
      conditions.
AB  - BACKGROUND: Although the new atypical antipsychotic, quetiapine fumarate, is
      growing in popularity over its progenitor, clozapine, clinical experience with
      overdose of this agent remains limited. Observation of an overdose situation
      provided a unique opportunity to define the safety, clinical effects, and
      pharmacokinetics of this medication more clearly. METHODS: A patient admitted
      immediately after ingesting an overdose of 30 tablets of 100 mg of quetiapine was
      observed carefully to document effects of the medication. These observations were
      compared with the only two other published cases of overdose, to the known
      pharmacology of the drug, and to serial measurements of serum drug concentrations
      obtained to document the time course of elimination of the drug. RESULTS:
      Consistent with the two previously published cases, the main clinical effects of
      overdose were hypotension, tachycardia, and somnolence as predicted by its known
      alpha-adrenergic receptor and histamine receptor blockade. These effects were
      managed with fluid resuscitation and supportive measures. No cardiac arrhythmias
      other than tachycardia have been reported, but the tachycardia was of an
      unexpectedly long duration in this case. Decline in serum quetiapine
      concentration followed a biexponential pattern with a terminal elimination half
      life of 22 hours. Unexpectedly low peak serum concentrations in three patients
      with overdose suggest that absorption is highly reduced, either by the effects of
      the overdose or by the activated charcoal administered. CONCLUSIONS: Quetiapine
      appears to have greater safety in overdose than traditional antipsychotic agents.
      Its toxicity is consistent with its receptor pharmacology. Elevated serum
      concentrations associated with this overdose remained above the limit of
      detection long enough to document a terminal elimination half-life of 22 hours in
      this patient. This is much more consistent with previously noted duration of
      clinical effects and detectable serum concentrations after overdose than the
      published half-life of 6 hours. Physicians should be aware that any new drug that
      is active at low concentrations may have had its half-life underestimated during
      preclinical development because of the difficulty in detecting the drug after the
      distribution phase has ended.

PMID- 10945321
TI  - Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living
      donor small bowel recipient.
AB  - We have examined whether the expression levels of the intestinal absorptive
      barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4 (CYP3A4),
      correlate with the trough levels of orally administered tacrolimus in a recipient
      of small bowel transplant for 4 months. By using a competitive polymerase chain
      reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by
      intestinal cells in a part of the mucosa biopsy specimen was evaluated. The
      average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/microg
      total RNA, respectively. Both the MDR1 and CYP3A4 mRNA levels changed markedly
      throughout this period. The tacrolimus concentration/dose ratio correlated well
      with the mRNA expression level of MDR1, but not CYP3A4. These results suggested
      that intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the
      intraindividual variation in the tacrolimus pharmacokinetics during
      immunosuppressant therapy after small bowel transplantation.

PMID- 10945322
TI  - Intermittent G-CSF (filgrastim) treatment cannot induce lymphocytosis in
      volunteers.

PMID- 10945323
TI  - Modulation imaging in reflection-mode near-field scanning optical microscopy
AB  - A simple implementation of modulation of the near-field optical signal of near
      field probes based on the shear-force feedback system is demonstrated in a
      reflection-mode near-field optical microscope. The modulation exhibits a
      derivative type of dependence on the near-field signal and no sensitivity to
      topography. It is shown that the modulation image can be calculated directly from
      the derivative of the conventional near-field scattering image. This type of near
      field modulation is an excellent way to reject far-field artifacts from the near
      field signal.

PMID- 10945324
TI  - Structure determination of phi-Bi8Pb5O17 by electron and powder X-ray diffraction
AB  - The triclinic crystal structure of phi-Bi8Pb5O17, a ionic fast conductor
      material, has been determined by the synergy of both electron and powder X-ray
      crystallography. The heavy atom positions were found by direct methods on
      electron diffraction data and the structure was completed by iterative use of a
      priori information in direct methods and difference Fourier maps on both types of
      data. Structure refinement was performed by the Rietveld method on powder X-ray
      data. The results suggest that phi-Bi8Pb5O17 is an ordered phase, with Bi and Pb
      atoms occupying different sites of the lattice, at variance with the other
      structural phases known for similar composition in the Bi-Pb-O phase diagram,
      which are solid solutions characterised by a wide compositional range.

PMID- 10945325
TI  - A simple and fast TEM preparation method utilizing the pre-orientation in plate
      like, needle-shaped and tubular materials
AB  - In order to observe anisotropically grown crystalline materials perpendicular to
      a certain preferred orientation, a standard cross-sectional TEM preparation
      method has been modified. The material is embedded in an organic epoxy resin
      between two Si-wafers. Plates, needles and tubes lay flat inside the resulting
      sandwich, which is then cut into slices perpendicular to the wafers. The slices
      are thinned by mechanical abrading and, finally, by ion milling. Crystals located
      near the central hole are electron-transparent, and their orientation often
      allows for an observation along the desired direction. The usefulness of this
      procedure is demonstrated on the examples of high-Tc superconductors and vanadium
      oxide nanotubes.

PMID- 10945326
TI  - Near-field scanning optical microscopy of zinc-porphyrin crystals.
AB  - Using a near-field scanning optical microscope (NSOM), crystals of zinc-porphyrin
      network materials are characterized with respect to morphology and fluorescence.
      Needle-shaped crystals are observed. While the topography is flat, the
      fluorescence intensity profile in the width direction is approximately
      triangular. A numerical calculation shows that differences between the
      topographic and optical images cannot be due to an artifact. In some needle
      shaped crystals, the fluorescence emission is strongly peaked at one or both
      ends, possibly indicating a polar crystal structure.

PMID- 10945327
TI  - Multiple scattering in low-energy electron holography
AB  - The theory of the low-energy electron point source (LEEPS) microscope is
      reformulated in matrix form to readily account for multiple scattering. An
      algorithm is developed for the storage of the structure matrix and an iterative
      method is used to solve the matrix equation for the structure factor. Examples of
      small and large clusters of atoms are given to compare single and multiple
      scattering. A Kirchhoff-Helmholtz transform is used for the reconstruction. We
      find that in some cases the multiple scattering is too strong and reconstruction
      is not possible. We give examples which show that, even when multiple scattering
      is important, one can still obtain reconstructions that reveal the atomic
      structure both along and lateral to the optical axis. We also compare our results
      with those found in LEED.

PMID- 10945328
TI  - On the calculation of the phase shift of superconducting fluxons: from the
      isolated to the lattice case
AB  - The numerical problems associated to the calculation of the phase shift due to a
      flux line lattice (FLL) in a thin superconducting specimen are presented and
      discussed. In order to be able to adequately treat the periodic case, the Fourier
      transform of the phase shift due to a flux tube is needed. This result is
      obtained by means of a new approach, where the phase shift is calculated from the
      beginning in the reciprocal space, treating separately each Fourier coefficient
      of the magnetic vector potential. The equivalence with the old approach is
      demonstrated and the utility of the new formulation for calculating the phase
      shift of closely packed FLL shown.

PMID- 10945329
TI  - Computed tomography of cryogenic biological specimens based on X-ray microscopic
      images.
AB  - Soft X-ray microscopy employs the photoelectric absorption contrast between water
      and protein in the 2.34-4.38 nm wavelength region to visualize protein structures
      down to 30 nm size without any staining methods. Due to the large depth of focus
      of the Fresnel zone plates used as X-ray objectives, computed tomography based on
      the X-ray microscopic images can be used to reconstruct the local linear
      absorption coefficient inside the three-dimensional specimen volume. High
      resolution X-ray images require a high specimen radiation dose, and a series of
      images taken at different viewing angles is needed for computed tomography.
      Therefore, cryo microscopy is necessary to preserve the structural integrity of
      hydrated biological specimens during image acquisition. The cryo transmission X
      ray microscope at the electron storage ring BESSY I (Berlin) was used to obtain a
      tilt series of images of the frozen-hydrated green alga Chlamydomonas
      reinhardtii. The living specimens were inserted into borosilicate glass
      capillaries and, in this first experiment, rapidly cooled by plunging into liquid
      nitrogen. The capillary specimen holders allow image acquisition over the full
      angular range of 180 degrees. The reconstruction shows for the first time details
      down to 60 nm size inside a frozen-hydrated biological specimen and conveys a
      clear impression of the internal structures. This technique is expected to be
      applicable to a wide range of biological specimens, such as the cell nucleus. It
      offers the possibility of imaging the three-dimensional structure of hydrated
      biological specimens close to their natural living state.

PMID- 10945330
TI  - New concept of information resolution in scanning electron microscope images
AB  - As a new means to evaluate SEM images from the viewpoint of image information, we
      have proposed information resolution, Rinf, defined as a spatial length per bit
      in information-passing capacity (IPC). The IPC densities (per basic area) were
      carried out by both taking into account the signal-to-noise ratio of the
      statistical mean power densities and applying a previously reported fitting
      functions to an optical system with an arbitrary size of aberration, diffraction
      (including lambda = 0), and source. Here, the nu-independent specimen contrast of
      tau(s)(nu)= 1 [used in Eq. (9)] is assumed. General characteristics on Rinf are
      typically plotted as a curve of log (Rinf/R(inf, ideal)) vs. log T, where T is
      (Bm2 + Cm4)(1/2), Bm and Cm are the modified spherical and chromatic aberrations,
      respectively. The subscript "ideal" represents an aberration-free optical system.
      The values of Rinf [calculated by Eq. (11)] are compared to those of the
      conventional beam size d [calculated by Eq. (1)] and the previously reported
      modified resolution Res [calculated by Eq. (7)]. It was found that R(inf, min)
      value is 0.3-0.9 times as small as the d(min) value and its corresponding beam
      semi-angle alpha(inf, min) is 1.2-1.8 times as large as the alpha(conv, min)
      value (depending on S/N).

PMID- 10945331
TI  - The spatial resolution of 3D atom probe in the investigation of single-phase
      materials
AB  - The resolution of three-dimensional atom probe (3DAP) is known to be mainly
      controlled by the aberrations of the ion trajectories near the surface of the
      specimen. A model has been developed to compute the ion trajectories in 3D near a
      sharp hemispherical electrode defined at the atomic scale. Simulations were
      applied on one-phase binary alloys. The influence of the evaporation fields of
      chemical species is studied. Simulated desorption images are consistent with
      experiments in both ordered alloys and random solid solution. An extra loss in
      the lateral resolution is observed in disordered alloys as compared to pure
      metals. The predicted order of evaporation provided by this model is in excellent
      agreement with experiments. The stacking sequence of atomic planes reconstructed
      from simulated data is shown to be disturbed in a similar way as observed in real
      experiments with 3DAP.

PMID- 10945332
TI  - TEM measurement of strain in coherent quantum heterostructures
AB  - We report on a transmission electron microscopy (TEM) technique that can be used
      to measure strain due to individual nanometer-scale coherent heterostructures
      such as quantum dots or inclusions. The measurement relies on two-beam imaging
      and on an approximation that employs a universal model for lattice plane bending.
      We demonstrate that analysis is simple and accurate. Using this method, we
      measured the average strain in dome-shaped Ge islands grown on Si (0 0 1). We
      found that the method of specimen preparation can significantly affect the
      observed strain in these islands.

PMID- 10945333
TI  - Integrating cellular and organismic aspects of vascular differentiation.
AB  - Vascular differentiation can be studied at two levels, and they should complement
      one another: as an aspect of integrated plant development and as cellular
      processes. The differentiation of organized strands that connect between organs
      is induced by polar auxin flow, towards the roots. Anatomy, therefore, can be a
      complementary method of observing polarity and its changes. As expected for a
      self-correcting and essential system, vascular patterning mutations are
      relatively rare and have pleiotropic effects, including modifications of
      responses to auxin and its transport. Tissue polarity both expresses and depends
      on auxin transport, a feedback that could account for the determined nature of
      polarity as well as the gradual canalization of differentiation to vascular
      strands. This predicts that the molecules responsible for polarity will be
      localized gradually as differentiation proceeds. Further, a modified location of
      these molecules can be expected to precede anatomical expressions of a new,
      regenerated, polarity. Tracheary differentiation is probably the best studied
      example of cell differentiation. Within the plant, however, this differentiation
      is coupled to oriented cell growth either along or at right angles to the axis of
      auxin flow, depending on tissue competence. Differentiation is also coupled to
      the differentiation of the other components of the vascular system. There are,
      presumably, early joint stages to these differentiation processes, but what they
      are remains an intriguing problem.

PMID- 10945334
TI  - Regulation of root growth by gibberellin in Lemna minor.
AB  - Hormonal control of root growth was studied in Lemna minor. Although addition of
      gibberellic acid (GA3) to the culture medium did not promote the root growth, a
      gibberellin biosynthesis inhibitor, uniconazole P (Un-P), significantly inhibited
      root growth. Both length and diameter of roots in Un-P-treated plants were
      significantly smaller than those in control plants, mainly caused by inhibition
      of cell division. In epidermal cells, the length was slightly decreased and the
      width increased by Un-P treatment, indicating inhibition of elongation growth.
      GA3 completely nullified the inhibition caused by Un-P. Transverse cortical
      microtubules (CMTs) of epidermal cells in the elongation zone were significantly
      fragmented by treatment with Un-P, but not by that in the presence of GA3. The
      cellulose microfibril array in the Un-P-treated cells was more random and more
      oblique than that in the control cells. These results suggested that root growth
      in L. minor is regulated by endogenous gibberellin.

PMID- 10945336
TI  - Cerebroside elicitors found in diverse phytopathogens activate defense responses
      in rice plants.
AB  - Cerebrosides A and C, compounds categorized as glycosphingolipids, were isolated
      in our previous study from the rice blast fungus (Magnaporthe grisea) as novel
      elicitors which induce the synthesis of rice phytoalexins. In this paper, these
      cerebroside elicitors showed phytoalexin-inducing activity when applied to plants
      by spray treatment and also induced the expression of pathogenesis-related (PR)
      proteins in rice leaves. This elicitor activity of the cerebrosides showed the
      structural specificity as that for the induction of phytoalexins. Ceramides
      prepared from the cerebrosides by removal of glucose also showed the elicitor
      activity even in lower level compared to the cerebrosides. In field experiments,
      the cerebroside elicitors effectively protected rice plants against the rice
      blast fungus, an economically devastating agent of disease of rice in Japan. The
      cerebrosides elicitors protected rice plants from other disease as well and were
      found to occur in a wide range of different phytopathogens, indicating that
      cerebrosides function as general elicitors in a wide variety of rice-pathogen
      interactions.

PMID- 10945335
TI  - Molecular characterization of tobacco mitochondrial L-galactono-gamma-lactone
      dehydrogenase and its expression in Escherichia coli.
AB  - A cDNA clone encoding L-galactono-gamma-lactone (GAL) dehydrogenase (EC 1.3.2.3)
      was isolated from tobacco leaves. The cDNA clone contained an open reading frame
      encoding the protein of 501 amino acids with a calculated molecular mass of
      56,926 Da, preceded by a putative mitochondrial targeting signal consisting of 86
      amino acid residues. In fact, GAL dehydrogenase was localized in the mitochondria
      of tobacco cells. The deduced amino acid sequence of the cDNA showed 77 and 82%
      homology to cauliflower and sweet potato GAL dehydrogenases, respectively.
      Southern blot analysis showed that tobacco contains one copy of the gene for the
      enzyme. Northern blot analysis showed that GAL dehydrogenase mRNA (2.0 kb) is
      expressed in the leaves, stems, and roots in almost equal quantities. We
      introduced the cDNA clone encoding tobacco GAL dehydrogenase into a pET
      expression vector to overexpress this protein in Escherichia coli. The partially
      purified recombinant enzyme was used for comparative studies on the native
      enzymes from tobacco and other sources; its enzymatic properties were similar to
      those of other GAL dehydrogenases.

PMID- 10945337
TI  - Screening of wound-responsive genes identifies an immediate-early expressed gene
      encoding a highly charged protein in mechanically wounded tobacco plants.
AB  - In order to identify genes that are temporally and spatially regulated during
      wound response, a cDNA population in mechanically wounded tobacco leaves was
      screened by the fluorescence differential display method. Of 28 clones initially
      identified to have altered levels of transcripts within 3 h of wounding, eight
      were characterized. Although each clone showed a unique pattern of transcript
      accumulation, one distinct clone was further characterized because of its
      immediate-early response. Its transcripts began to accumulate 10 min after
      wounding, reached a maximum level within 1 h and disappeared after 2 h. The
      response, which occurred repeatably and systemically, was observed by the
      treatment with propionic acid or erythrosin B, indicating that cytosolic
      acidification could be one of the signals for immediate-early response of this
      gene. The cDNA encodes a polypeptide of 513 amino acids with a relative molecular
      mass of 60,952. The putative polypeptide is rich in lysine (K), glutamic acid (E)
      and aspartic acid (D), which constitute up to 70% of total amino acids, and was
      therefore designated as KED. The KED polypeptide is composed of a highly
      hydrophilic N-terminal region and a relatively hydrophobic C-terminal region,
      suggesting that KED may function through electrostatic interactions with cellular
      components.

PMID- 10945338
TI  - Phytophthora parasitica elicitor-induced reactions in cells of Petroselinum
      crispum.
AB  - Cultured parsley (Petroselinum crispum) cells respond to treatment with elicitors
      derived from different species of the genus Phytophthora with transcript
      accumulation of defense-associated genes and the production of furanocoumarin
      phytoalexins. Pep-25, an oligopeptide fragment of a Phytophthora sojae 42-kDa
      cell wall protein, and a cell wall elicitor preparation derived from Phytophthora
      parasitica (Pp-elicitor) stimulate accumulation of the same gene transcripts and
      formation of the same pattern of furanocoumarins. Treatment of cultured cells and
      protoplasts with proteinase-digested Pp-elicitor identified proteinaceous
      constituents as active eliciting compounds in parsley. Similar to Pep- 25, Pp
      elicitor induced effluxes of K+ and Cl- and influxes of protons and Ca2+.
      Concomitantly, as monitored in aequorin-transgenic parsley cell lines both
      elicitors induced an immediate increase in the cytoplasmic Ca2+ concentration up
      to sustained levels of 175 nM (Pp-elicitor) or 300 nM (Pep-25), respectively. The
      signature of the Ca2+ response differed greatly between the two elicitors tested.
      Extracellular Ca2+ proved essential for activation of an oxidative burst, MAP
      kinase activity and phytoalexin production by either elicitor. While Pp-elicitor
      induced a qualitatively similar spectrum of defense responses as did Pep-25,
      elicitor-specific quantitative differences in response intensity and kinetics
      suggest activation of a conserved signaling cascade through separate ligand
      binding sites.

PMID- 10945339
TI  - Curvature in Arabidopsis inflorescence stems is limited to the region of
      amyloplast displacement.
AB  - Gravitropic sensing in stems and stem-like organs is hypothesized to occur in the
      endodermis. However, since the endodermis runs the entire length of the stem, the
      precise site of gravisensing has been difficult to define. In this investigation
      of gravisensitivity in inflorescence stems of Arabidopsis, we positioned stems in
      a high gradient magnetic field (HGMF) on a rotating clinostat. Approximately 40%
      of the young, wild-type (WT) inflorescences, for all positions tested, curved
      toward the HGMF in the vicinity of the stem exposed to the field. In contrast,
      when the wedge was placed in the basal region of older inflorescence stems, no
      curvature was observed. As a control, the HGMF was applied to a starchless
      mutant, and 5% of the stems curved toward the field. Microscopy of the endodermis
      in the WT showed amyloplast displacement in the vicinity of the HGMF. Additional
      structural studies demonstrated that the basal region of WT stems experienced
      amyloplast displacement and, therefore, suggest this region is capable of gravity
      perception. However, increased lignification likely prevented curvature in the
      basal region. The lack of apical curvature after basal amyloplast displacement
      indicates that gravity perception in the base is not transmitted to the apex.
      Thus, these results provide evidence that the signal (and thus, response)
      resulting from perception in Arabidopsis inflorescence stems is spatially
      restricted.

PMID- 10945340
TI  - Spatially and temporally regulated expression of rice MADS box genes with
      similarity to Arabidopsis class A, B and C genes.
AB  - The floral morphology of grass species is distinct from that of typical dicot
      plants. In order to achieve a better understanding of the molecular basis for
      this diversion, we isolated RAP1A, RAP1B and RAG, putative rice orthologs for the
      Arabidopsis class A gene APETALA1 (AP1) and class C gene AGAMOUS (AG). The
      expression patterns of RAP1A, RAG and OsMADS2, a rice ortholog of the class B
      gene, were analyzed by in situ hybridization. RAP1A mRNA was expressed in the
      apical region of the floral meristem at an early stage of spikelet development,
      and then its expression was localized in developing lemma, palea and lodicules.
      The OsMADS2 transcript was first observed in the region where stamen primordia
      are formed. Soon after, OsMADS2 mRNA appeared in the lodicule primordia as well
      as the stamen primordia, and this RNA accumulation pattern persisted until late
      stages of floral development. The expression of RAG was observed in stamens and
      pistils of wild-type young spikelets. These RNA accumulation patterns are mostly
      similar to those of Arabidopsis class A, B, C genes, supporting the notion that
      the ABC model may be extended to rice.

PMID- 10945341
TI  - Expression of the PIP aquaporin promoter-MipA from the common ice plant in
      tobacco.
AB  - The reasons for the presence of a multitude of plasma membrane-localized water
      channels (PIP aquaporins) in plants may be functional differences in water (or
      other solute) transport, or in developmental, environmental or tissue-specific
      regulation of expression. We compared tissue- and cell-specific expression of
      McMipA, an abundantly expressed PIP from the common ice plant (Mesembryanthemum
      crystallinum), with that of the previously characterized McMipB [Yamada et al.
      (1997) Plant Cell Physiol. 38: 1326]. The activity of a 2.2 kb DNA fragment
      containing the promoter region of McMipA in a fusion with the GUS coding region
      was studied in transgenic tobacco. The McMipA promoter was active in pericycle
      and cortex cells in roots and in phloem-associated cells and cells surrounding
      the pericycle in shoots. In green leaves, mesophyll cells and the minor veins
      showed GUS activity, but the major veins did not. In floral tissues, GUS activity
      was observed in the pistil and anthers of immature buds and the tip of the mature
      pistil and pollen. Neither the apical meristem nor root tip showed any GUS
      activity. The differences in tissue specificity between the McMipA and McMipB
      promoters indicated that the two PIPs, MC-MIPA and MC-MIPB, serve different
      functions in plants.

PMID- 10945342
TI  - Isolation of two different phenotypes of mycorrhizal mutants in the model legume
      plant Lotus japonicus after EMS-treatment.
AB  - Lotus japonicus has been proposed as a model plant for the molecular genetic
      study of plant-microbe interaction including Mesorhizobium loti and arbuscular
      mycorrhizal (AM) fungi. Non-mycorrhizal mutants of Lotus japonicus were screened
      from a collection of 12 mutants showing non-nodulating (Nod-), ineffectively
      nodulating (Fix-) and hypernodulating (Nod++) phenotypes with monogenic recessive
      inheritance induced by EMS (ethylmethane sulfonate) mutagenesis. Three
      mycorrhizal mutant lines showing highly reduced arbuscular mycorrhizal
      colonization were obtained. All of them were derived from Nod- phenotypes. In
      Ljsym72, the root colonization by Glomus sp. R-10 is characterized by poor
      development of the external mycelium, formation of extremely branched
      appressoria, and the blocking of hyphal penetration at the root epidermis.
      Neither arbuscules nor vesicles were formed in Ljsym72 roots. Fungal recognition
      on the root surface was strongly affected by the mutation in the LjSym72 gene.
      Unique characteristics in mutant lines Ljsym71-1 and Ljsym71-2 were the
      overproduction of deformed appressoria and arrested hyphal penetration of the
      exodermis. Small amounts of internal colonization including degenerated arbuscule
      formation occurred infrequently in these types of mutants. Not only fungal
      development on the root surface but also that in the root exodermis and cortex
      was affected by the mutation in LjSym71 gene. These mutants represent a key
      advance in molecular research on the AM symbiosis.

PMID- 10945343
TI  - Frequency and pattern of transposition of the maize transposable element Ds in
      transgenic rice plants.
AB  - Two kinds of T-DNA constructs, I-RS/dAc-I-RS and Hm(R)Ds, carrying a non
      autonomous transposable element of Ac of maize were introduced into rice plants
      by Agrobacterium-mediated gene transfer. Six transgenic rice plants identified as
      containing a single copy of the element were crossed with two transgenic rice
      plants carrying a gene for Ac transposase under the control of the cauliflower
      mosaic virus 35S promoter. In F2 progenies, excision of the element was detected
      by PCR analysis and re-integration of the element was investigated by Southern
      blot analysis. The frequency of the excision of the element was found to vary
      from 0 to 70% depending on the crossing combination. The frequency of the number
      of individual transposition events out of the total number of F2 plants with
      germinal excision was 44% in one crossing combination and 38% in the other. In
      the most efficient case, 10 plants with independent transposition were obtained
      out of the 49 F2 plants tested. Linkage analysis of the empty donor site and the
      transposed Ds-insertion site in F3 plants demonstrated that one of five Ds
      insertion sites was not linked to the empty donor site. The transgenic rice
      obtained in this study can be used for functional genomics of rice.

PMID- 10945344
TI  - Transgenic rice plants expressing a Bacillus subtilis protoporphyrinogen oxidase
      gene are resistant to diphenyl ether herbicide oxyfluorfen.
AB  - Protoporphyrinogen oxidase (Protox), the penultimate step enzyme of the branch
      point for the biosynthetic pathway of Chl and hemes, is the target site of action
      of diphenyl ether (DPE) herbicides. However, Bacillus subtilis Protox is known to
      be resistant to the herbicides. In order to develop the herbicide-resistant
      plants, the transgenic rice plants were generated via expression of B. subtilis
      Protox gene under ubiquitin promoter targeted to the cytoplasm or to the plastid
      using Agrobacterium-mediated gene transformation. The integration and expression
      of the transgene were investigated at T0 generation by DNA and RNA blots. Most
      transgenic rice plants revealed one copy transgene insertion into the rice
      genome, but some with 3 copies. The expression levels of B. subtilis Protox mRNA
      appeared to correlate with the copy number. Furthermore, the plastidal transgenic
      lines exhibited much higher expression of the Protox mRNA than the cytoplasmic
      transgenic lines. The transgenic plants expressing the B. subtilis Protox gene at
      T0 generation were found to be resistant to oxyfluorfen when judged by cellular
      damage with respect to cellular leakage, Chl loss, and lipid peroxidation. The
      transgenic rice plants targeted to the plastid exhibited higher resistance to the
      herbicide than the transgenic plants targeted to the cytoplasm. In addition,
      possible resistance mechanisms in the transgenic plants to DPE herbicides are
      discussed.

PMID- 10945345
TI  - Molecular cloning and characterization of a cDNA encoding proline transporter in
      rice.
AB  - A cDNA encoding a proline (Pro) transporter (ProT) was isolated and characterized
      from a cDNA library prepared from 14-d-old seedlings of Oryza sativa cv. Akibare.
      The deduced amino acid sequence of the rice ProT protein (OsProT) had 68.8%
      homology to the ProT protein 1 from Arabidopsis thaliana and 59.6% homology to
      that from Lycopersicon esculentum. Northern blot analysis revealed that the gene
      for OsProT (OsProT) was expressed in all organs examined, comparatively strongly
      in leaf sheath and stem. Salt treatment did not induce expression of OsProT but
      strongly induced expression of the gene for delta1-pyrroline-5-carboxylate
      synthetase (P5CS), a key enzyme in Pro biosynthesis. Southern blot analysis
      revealed that OsProT has a gene family. OsProT specifically transported L-Pro in
      a transport assay using Xenopus laevis oocytes.

PMID- 10945346
TI  - Expression of Bra r 1 gene in transgenic tobacco and Bra r 1 promoter activity in
      pollen of various plant species.
AB  - Bra r 1 encodes a Ca2+-binding protein specifically expressed in anthers of
      Brassica rapa. In this study, we isolated a genomic clone of Bra r 1 and found
      sequences similar to Pollen Box core motifs and LAT56/59 box, pollen-specific cis
      acting element, in the 5' upstream region of Bra r 1. Reporter gene fusion
      revealed that the Bra r 1 promoter directs male gametophytic expression in
      Nicotiana tabacum, Arabidopsis thaliana and B. napus, showing strong expression
      in mature pollen grains similar to that of endogenous Bra r 1. Genomic DNA of Bra
      r 1 was introduced into tobacco plants and the highest accumulation of Bra r 1
      protein was observed in mature pollen in the same manner as reporter gene
      expression. Using in vitro-germinated pollen tubes of transgenic tobacco, we
      firstly demonstrated the subcellular localization of Bra r 1 in pollen tubes. Bra
      r 1 protein was distributed throughout the pollen tube of transgenic tobacco and
      slightly intense signals of Bra r 1 were observed in the tip region. In long
      germinated pollen tubes, Bra r 1 was detected only in the cytoplasmic
      compartments while no signals were observed in the empty part of the pollen tube,
      indicating that cytoplasmic movement toward the tube tip is accompanied by Bra r
      1. Hence, we suggest that Bra r 1 is involved in pollen germination and pollen
      tube growth.

PMID- 10945347
TI  - Photosynthetic acclimation of the filamentous cyanobacterium, Plectonema boryanum
      UTEX 485, to temperature and light.
AB  - Photosynthetic acclimation to temperature and irradiance was studied in the
      filamentous, non-heterocystous cyanobacterium Plectonema boryanum UTEX 485.
      Growth rates of this cyanobacterium measured at ambient CO2 were primarily
      influenced by temperature with minimal effects of irradiance. Both growth
      temperature and irradiance affected linolenic (18:3) and linoleic acid (18:2)
      levels in the four major lipid classes in an independent but additive manner. In
      contrast, photosynthetic acclimation was not due to either growth temperature or
      irradiance per se, but rather, due to the interaction of these environmental
      factors. P. boryanum grown at low temperature and moderate irradiance mimicked
      cells grown at high light. Compared to cells grown at either 29 degrees C/150
      micromol m(-2) s(-1) (29/150) or 15/10, P. boryanum grown at either 15/150 or
      29/750 exhibited: (1) reduced cellular levels of Chl a and phycobilisomes (PBS),
      and concomitantly higher content of an orange-red carotenoid, myxoxanthophyll;
      (2) higher light saturated rates (Pmax) when expressed on a Chl a basis but lower
      apparent quantum yields of oxygen evolution and (3) enhanced resistance to high
      light stress. P. boryanum grown at 15/150 regained normal blue-green pigmentation
      within 16 h after a temperature shift to 29 degrees C at a constant irradiance of
      150 micromol m(-2) s(-1). DBMIB and KCN but not DCMU and atrazine partially
      inhibited the change in myxoxanthophyll/Chl a ratio following the shift from 15
      to 29 degrees C. We conclude that P. boryanum responds to either varying growth
      temperature or varying growth irradiance by adjusting the ability to absorb light
      through decreasing the cellular contents of Chl a and light-harvesting pigments
      and screening of excessive light by myxoxanthophyll predominantly localized in
      the cell wall/cell membrane to protect PSII from over-excitation. The possible
      role of redox sensing/signalling for photosynthetic acclimation of cyanobacteria
      to either temperature or irradiance is discussed.

PMID- 10945348
TI  - Specific accumulation of polysaccharide-linked hydroxycinnamoyl esters in the
      cell walls of irregularly shaped and collapsed internode parenchyma cells of the
      dwarf rice mutant Fukei 71.
AB  - We examined a novel rice mutant, Fukei 71 (Oryza sativa L.), for alterations in
      the levels of hydroxycinnamoyl esters that are linked to cell wall
      polysaccharides and lignin units. In this mutant, a recessive mutation at a
      single locus caused the collapse of parenchyma cells in the internodes. Light
      microscopy revealed that the abnormal walls of internode parenchyma cells of
      Fukei 71 were stained by the Maule reaction, which is specific for syringyl units
      in phenolic compounds. These walls were not stained by Wiesner's reagent
      (phloroglucinol-HCl), which reacts cinnamaldehyde in lignin. Levels of p-coumaric
      acid (PCA) and ferulic acid (FA) were apparently elevated in the abnormal tissue
      of the mutant. Western blotting analysis with antibodies specific for
      phenylalanine ammonia-lyase (PAL) revealed higher levels of PAL in the abnormal
      parenchyma tissue of Fukei 71 than in the parenchyma tissue of the parent
      cultivar Fujiminori. These results and the observation that PAL was produced at a
      greatly elevated level indicated that the phenylpropanoid pathway that leads to
      the biosynthesis of polysaccharide-linked FA and PCA was abnormally activated in
      the irregularly shaped and collapsed internode parenchyma cells, in which the
      biosynthesis of lignin is normally repressed.

PMID- 10945349
TI  - Co-expression of calcium-dependent protein kinase with the inward rectified guard
      cell K+ channel KAT1 alters current parameters in Xenopus laevis oocytes.
AB  - Increased guard cell cytosolic [Ca2+] is known to be involved in signal
      transduction pathways leading to stomatal closure, and inhibit the inward
      rectifying guard cell K+ channel KAT1. Guard cell calcium-dependent protein
      kinase (CDPK) has been shown to phosphorylate KAT1; such phosphorylation is known
      to modulate other K+ channels involved in signal transduction cascades. The work
      reported here focused on demonstrating CDPK-dependent inhibition of KAT1
      currents. A cDNA encoding soybean CDPK was generated and it's translation product
      was shown to be functional; demonstrating Ca2+-dependent autophosphorylation and
      phosphorylation of a target protein. Ion currents were monitored using voltage
      clamp techniques upon expression of KAT1 in Xenopus laevis oocytes. Coexpression
      of recombinant CDPK with KAT1 in oocytes altered the kinetics and magnitude of
      induced K+ currents; at a given hyperpolarizing command voltage, the magnitude of
      KAT1 currents was reduced and the half-time for channel activation was increased.
      This finding supports a model of Ca2+-dependent ABA inhibition of inward K+
      currents in guard cells as being mediated by CDPK phosphorylation of KAT1.

PMID- 10945351
TI  - Binding of the maize cytosolic Hsp70 to calmodulin, and identification of
      calmodulin-binding site in Hsp70.
AB  - Using a gel-overlay technique of biotinylated calmodulin (CaM), we showed that
      maize cytosolic Hsp70 protein could bind to CaM in the presence of 1 mM CaCl2.
      The purified maize cytosolic Hsp70 inhibited the activity of CaM-dependent NADK
      in a concentration-dependent manner. A synthetic peptide, which possesses the 21
      amino acid sequence, PRALRRLRTACERAKRTLSST, at positions 261-281 in maize
      cytosolic Hsp70, could associate with CaM in the presence of 1 mM calcium. The
      synthetic peptide inhibited CaM-dependent NADK activity and PDE activity. This
      indicates that the 21-amino acid sequence at positions 261-281 is the CaM-binding
      site. The binding of CaM to Hsp70 inhibited the ATPase activity of Hsp70. The
      possible regulator function of Hsp70 in cell signaling events in response to heat
      stress is discussed.

PMID- 10945350
TI  - Genes encoding pseudo-response regulators: insight into His-to-Asp phosphorelay
      and circadian rhythm in Arabidopsis thaliana.
AB  - In the higher plant, Arabidopsis thaliana, results from recent intensive studies
      suggested that His-to-Asp phosphorelay mechanisms are involved presumably in
      propagation of environmental stimuli, such as phytohormones (e.g. ethylene and
      cytokinin). Here we identified and characterized a set of novel Arabidopsis genes
      whose products considerably resemble the authentic response regulators (ARR
      series) of Arabidopsis in the sense that they have a phospho-accepting receiver
      like domain. However, they should be discriminated from the classical ones in the
      strict sense that they lack the invariant phospho-accepting aspartate site. They
      were thus named APRRs (Arabidopsis pseudo-response regulators). Two such
      representatives, APRR1 and APRR2, were characterized extensively through cloning
      of the corresponding cDNAs, in terms of their structural designs, biochemical
      properties, subcellular localization in plant cells, and expression profiles at
      the transcriptional level. The result of in vitro phosphorylation experiment with
      the Arabidopsis AHP phosphotransmitter suggested that the pseudo-receivers have
      no ability to undergo phosphorylation. The result of transient expression assay
      with onion epidermal cells showed that the GFP-APRR1 fusion protein has an
      ability to enter into the nuclei. The C-terminal domain of APRR1, termed CONSTANS
      motif, appears to be responsible for the nuclear-localization. The most
      intriguing result was that the accumulation of APRR1 transcript is subjected to a
      circadian rhythm. The APRR1 protein is identical to the one that was recently
      suggested to interact with the ABI3 (ABISCISIC ACID INSENSITIVE3) protein. These
      are discussed with special reference to the His-to-Asp phosphorelay signal
      transduction and circadian rhythm in Arabidopsis thaliana.

PMID- 10945352
TI  - A rapid and efficient system of Agrobacterium infection-mediated transient gene
      expression in rice Oc cells and its application for analysis of the expression
      and antisense suppression of preprophytosulfokine, a precursor of phytosulfokine
      a, encoded by OsPSK gene.
AB  - A rapid and efficient system for Agrobacterium infection-mediated transient gene
      expression in rice has been developed. Using this system, transient expression of
      preprophytosulfokine, a precursor of phytosulfokine-a, encoded by OsPSK gene was
      analyzed. The results suggest that the Agrobacterium infection-mediated transient
      gene expression system is as efficient in rice Oc cells as in tobacco BY-2 cells
      and might be useful for rapid analysis not only of foreign gene expression, but
      also of antisense gene suppression.

PMID- 10945353
TI  - Characterization of gene expression of NsERFs, transcription factors of basic PR
      genes from Nicotiana sylvestris.
AB  - Three genes of NsERFs (EREBPs), transcription factors for GCC box of basic PR
      genes, were isolated from Nicotiana sylvestris. Analyses of transgenic tobacco
      carrying the NsERF promoter::GUS genes showed that expression of all NsERF genes
      in leaves was induced by ethylene. Sequence analyses indicated that the 5'
      upstream region of NsERF3 gene has the GCC box. In contrast, the promoter regions
      of NsERF2 and 4 have no GCC box, whereas NsERF2 has a putative EIN3 binding site.
      Tissue/cell specific expression is also discussed.

PMID- 10945354
TI  - Length of stay has minimal impact on the cost of hospital admission.
AB  - BACKGROUND: Hospital cost containment, cost reduction, and alternative care
      delivery systems continue to preoccupy health care providers, payers, employers,
      and policy makers throughout the United States. The universal metric for gauging
      the success of these efforts is hospital length of stay (LOS). Reducing the LOS
      purportedly yields large cost savings. The purpose of this study is to assess
      precisely how much hospitals save by shortening LOS. STUDY DESIGN: We reviewed
      the cost-accounting records of all surviving patients (n = 12,365) discharged
      from our academic medical center during fiscal year 1998 with LOS of 4 days or
      more. Actual costs were identified through the University of Michigan cost
      accounting system. Individual patient costs were broken out on a daily basis and
      then decomposed further into variable direct, fixed direct, and indirect
      categories. The population was analyzed by determining the incremental resource
      cost of the last full day of stay versus the total cost for the entire stay. The
      data were also stratified by LOS and by surgical costs. An analysis of all trauma
      patients was then performed on all patients discharged from the hospital's adult
      level I trauma center (n = 665). Costs were determined on specific days,
      including admission day, each ICU day, day of discharge from the ICU, and each of
      the last 2 days before the discharge day. RESULTS: The incremental costs incurred
      by patients on their last full day of hospital stay were $420 per day on average,
      or just 2.4% of the $17,734 mean total cost of stay for all 12,365 patients. Mean
      end-of-stay costs represented only a slightly higher percentage of total costs
      when LOS was short (e.g., 6.8% for patients with LOS of 4 days). Even when the
      data were stratified to focus on patients without major operations, the $432
      average last-day variable direct cost was only 3.4% of the $12,631 average total
      cost of care. A focus on the trauma center helps to explain this phenomenon. For
      our trauma center, variable direct costs accounted for 42% of the mean total cost
      per patient of $22,067. The remaining 58% was hospital overhead (fixed and
      indirect costs). The median variable direct cost on the first day of admission is
      $1,246, and the median variable direct cost on discharge is $304. Approximately
      40% of the variable costs are incurred during the first 3 days of admission.
      CONCLUSIONS: For most patients, the costs directly attributable to the last day
      of a hospital stay are an economically insignificant component of total costs.
      Reducing LOS by as much as 1 full day reduces the total cost of care on average
      by 3% or less. Going forward, physicians and administrators must deemphasize LOS
      and focus instead on process changes that better use capacity and alter care
      delivery during the early stages of admission, when resource consumption is most
      intense.

PMID- 10945355
TI  - Prevention of adhesions to polypropylene mesh in a traumatized bowel model.
AB  - BACKGROUND: Polypropylene mesh (PPM) is an effective material for the repair of
      abdominal wall defects, but has a tendency to induce dense adhesions when in
      contact with viscera. Seprafilm (Genzyme Corp, Cambridge, MA), a bioresorbable
      membrane, has been shown to reduce adhesion formation after midline closures in
      humans and to PPM in animals. Given the increased inflammatory response expected
      with surgical trauma, its efficacy under surgical conditions has been questioned.
      STUDY DESIGN: A prospective, randomized, blinded study was conducted using a
      rabbit model. Standardized abdominal wall defects were created in three groups of
      New Zealand white rabbits. The cecum was deserosalized to simulate the effects of
      trauma. The abdominal defect was then repaired with PPM. In the control group, no
      Seprafilm was used. In the first experimental group Seprafilm was placed between
      the mesh and the abdominal viscera. In the second experimental group Seprafilm
      was placed over the deserosalized area and between the mesh and abdominal
      viscera. Animals were sacrificed at 30 days and adhesions were categorized and
      quantified using digital image analysis of inked specimens. The strength of
      incorporation was also determined. RESULTS: The formation of adhesions between
      the viscera and mesh repair was dramatically reduced in both experimental groups
      compared with the control group. The incidence of visceral adhesions was reduced
      by 80% in the single film group (p = 0.0004) and 90% in the double film group (p
      = 0.00008). The reduction in surface area of adhesions was 96.4% in the single
      film group (p = 0.000019) and 99.4% in the double film group (p = 0.00002).
      Omental adhesions were reduced by 30% but this did not achieve statistical
      significance. Strength of incorporation was not adversely affected in either
      group. CONCLUSIONS: Seprafilm is highly effective in preventing adhesions to PPM.
      This effect was not diminished by the presence of visceral trauma and its
      resultant inflammatory response. The use of Seprafilm does not adversely affect
      tissue incorporation. Clinical trials are warranted to determine if the
      protective effects of Seprafilm demonstrated in this study are applicable in the
      clinical setting.

PMID- 10945356
TI  - Surgical management of groin pain of neural origin.
AB  - BACKGROUND: An approach to surgical management of the patient with groin pain is
      described based on our experience with 54 patients, six of whom had bilateral
      symptoms. History and physical examination are sufficient to relate the pain to
      one or more of the lateral femoral cutaneous (LFC), ilioinguinal (II),
      iliohypogastric (IH), or genitofemoral (GF) nerves. STUDY DESIGN: Retrospective
      analysis of patients with groin pain is reported, with emphasis on cause,
      involved nerves, and outcomes of operative management. The LFC was decompressed.
      The II, IH, and GF nerves were resected. Outcomes were graded as excellent, good,
      and poor in terms of pain relief and functional restoration. RESULTS: For the
      entire series of patients with painful groins, excellent relief of pain was
      achieved in 68% and restoration of function achieved in 72%. Ten percent had a
      poor result. The best results were for II and IH, which were 78% and 83%
      excellent for both pain relief and restoration of function, with 11% and 17%
      having a poor result, respectively. The worst results were for the small group of
      patients with a GF problem, 50% of whom had an excellent and 25% a poor result.
      Patients who were likely to get an LFC entrapment were those with a nerve located
      above or within the inguinal ligament. Complications included bruising and
      cautery injury to the LFC. CONCLUSIONS: Groin pain of neural origin can be
      relieved with a high degree of patient satisfaction by considering whether one or
      more of four different nerves are the source of that pain, by realizing that
      symptoms can be referred to regions other than the groin, such as the pelvic
      viscera (IH), the knee (LFC), and the testicle (GF), and by treating the
      appropriate nerve(s) by either neurolysis (LFC) or resection.

PMID- 10945357
TI  - The recurrence pattern of esophageal carcinoma after transhiatal resection.
AB  - BACKGROUND: There is much controversy about the optimal resection for carcinoma
      of the esophagus. Little is known about the pattern of recurrence after
      transhiatal resection for esophageal carcinoma. STUDY DESIGN: We retrospectively
      reviewed the charts of 149 patients who underwent transhiatal esophagectomy for
      carcinoma of the mid or distal esophagus or gastroesophageal junction between
      June 1993 and June 1997. Recurrence was classified as locoregional or distant
      recurrence. Nine patients with macroscopically evident tumor left after resection
      and three patients (2.0%) who died in the hospital were excluded from the
      analysis. This left 137 patients; 105 men and 32 women with a median age 65 years
      (range 37 to 84 years). RESULTS: There were 95 adenocarcinomas (69.3%) and 42
      squamous cell carcinomas (30.7%). Overall the median followup was 24.0 months
      (range 1.4 to 69.2 months). For patients alive at the end offollowup without
      recurrence, the median followup was 36.5 months (range 23.6 to 69.2 months).
      Seven patients died of other causes. The median interval between operation and
      recurrence was 11 months (range 1.4 to 62.5 months) for patients who had
      recurrence, with no significant difference in interval between locoregional and
      systemic recurrence. Seventy-two of the 137 patients (52.6%) developed recurrent
      disease. Thirty-two patients (23.4%) developed locoregional recurrence only, 21
      patients (15.3%) developed systemic recurrence only, and 19 patients (13.9%) had
      a combination of both. In only 8.0% of all patients was there recurrence in the
      cervical lymph nodes. The most frequent sites of distant recurrence were liver
      (37.5%), bone (25.0%), and lung (17.5%). Recurrence was related to postoperative
      lymph node status (p<0.001) and the radicality of the operation (p<0.001) in
      multivariate analysis. Recurrence was not associated with localization or
      histologic type of the tumor. CONCLUSIONS: Recurrence after transhiatal resection
      is an early event. Almost 40% of patients developed locoregional recurrent
      disease. For this patient group a more extended procedure may be of benefit,
      especially in the patients (23.4%) with locoregional recurrence in whom this is
      the only site of recurrent disease. But the potential benefit of a more extended
      procedure has to be balanced against a possible increase in perioperative
      morbidity and mortality.

PMID- 10945358
TI  - A comparison study of laparoscopic versus open gastric bypass for morbid obesity.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (GBP) has been previously
      described, but a comparative study between laparoscopic and open GBP has not been
      reported. The purpose of this study was to compare surgical outcomes
      oflaparoscopic GBP with those of open GBP for treatment of morbid obesity. STUDY
      DESIGN: From August 1998 to September 1999, we prospectively collected outcome
      data on 35 patients with body-mass indices between 40 kg/m2 and 60 kg/m2 who
      underwent laparoscopic GBP. Demographics, operative data, perioperative
      complications, and weight losses were collected and compared with those obtained
      from a retrospective chart review of 35 patients with body-mass indices between
      40 kg/m2 and 60 kg/m2 who underwent open GBP before August 1998. RESULTS: Age,
      gender, preoperative body-mass index, preoperative comorbidity, and earlier
      abdominal surgery were similar in both groups. All laparoscopic operations were
      completed without conversion to laparotomy. Mean operative time, operative blood
      loss, length of intensive care stay, and length of hospital stay were
      significantly less after laparoscopic GBP than after open GBP (p<0.05). There was
      no 30-day mortality in either group. At 1-year followup, analysis of the
      percentage of excess body weight loss showed no significant difference between
      the two groups (p<0.05). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass is
      technically feasible and safe. Laparoscopic GBP confers the clinical benefits of
      laparoscopy and an initial weight loss similar to that of open GBP.

PMID- 10945359
TI  - Laparoscopic cholecystectomy in the treatment of patients with gall bladder
      cancer.
AB  - BACKGROUND: Surgical procedures based on the depth of the primary tumor invasion
      (pT category) have been proposed in the treatment of gallbladder cancer (GBC).
      Trocar site metastases have been reported in patients who underwent laparoscopic
      cholecystectomy (LC) for preoperatively undiagnosed GBC. STUDY DESIGN: The aim of
      this study was to clarify the role of LC as a surgical strategy for GBC. From
      1986 to 1998, 56 patients with GBC underwent surgical resection. Survival rates
      were compared retrospectively according to pT category and use of LC. RESULTS:
      Five-year survival was 91% for pT1 (n = 13), 64% for pT2 (n = 25), 34% for pT3 (n
      = 14), and 0% for pT4 tumors (n = 4; p<0.0001). LC was performed on 11 patients
      (4 with pT1, 5 with pT2, and 2 with pT3 tumors). Of the seven patients with pT2
      or pT3 tumors, three underwent a second radical operation, three had an open
      radical operation to which the procedure was converted from LC, and one underwent
      no additional procedures. For pT1 tumors, one patient died of trocar site
      metastasis from bile spillage after LC. For pT2 or pT3 tumors, 5-year survival
      was 63% for radical surgery (n = 35) and 0% for cholecystectomy alone (n = 4;
      p<0.05). For pT2 or pT3 tumors treated by radical surgery, 5-year survival was
      75% for laparoscopic approach (n = 6) and 60% for open surgery (n = 29; not
      significant). CONCLUSIONS: LC may help to establish the diagnosis and to
      determine the surgical strategy for undiagnosed GBC. It is important to prevent
      spillage or implantation of malignant cells during LC. For pT2 or pT3 tumors
      diagnosed laparoscopically, a second or converted open radical surgery is
      necessary.

PMID- 10945360
TI  - Focal hepatic ablation using interstitial photon radiation energy.
AB  - BACKGROUND: Intratumoral ablative therapy is being used increasingly for the
      treatment of primary and secondary hepatic malignancies. The interstitial point
      source photon radiosurgery system (PRS) is a novel ablative technique that uses
      radiation therapy similar in dosimetry to interstitial brachytherapy. STUDY
      DESIGN: To determine the feasibility, toxicity, and local tissue destructive
      capabilities of the PRS in the liver, preliminary studies in a nontumor-bearing
      canine model were examined. A 6-month survival study was conducted. Each animal
      received three radiation treatments, in the right, central, and left hepatic
      regions. Three low-dose treatments were delivered to each of six animals (group
      A), generating a 2.0-cm-diameter radiated sphere with a dose of 20 Gy at the
      lesion edge. Three high-dose treatments were delivered to each of six animals
      (group B), generating a 3.0-cm-diameter radiated sphere with 20 Gy at the lesion
      edge. RESULTS: The treatment reproducibly generated sharply demarcated hepatic
      ablative lesions proportional to the administered dose. Mean lesion diameter at 1
      month was 1.6+/-0.2 cm in group A and 3.4+/-1.0 cm in group B. Lesion size was
      independent of intrahepatic location, including near vascular structures. PRS
      therapy, when applied to portal structures, resulted in hilar damage. Hilar
      damage appeared to be associated with arteriolar thrombosis and bile duct injury.
      Treatment of regions adjacent to large hepatic veins and the IVC was not
      associated with vessel thrombosis or stricture. CONCLUSIONS: PRS ablation is a
      generally well-tolerated method that results in consistent, well-demarcated,
      symmetric lesions of complete necrosis with minimal adjacent parenchymal injury.
      Application of such an approach for the treatment of liver tumors is promising.

PMID- 10945361
TI  - Surgical management of desmoid tumors of the female pelvis.
AB  - BACKGROUND: Desmoid tumors are neoplasms characterized by proliferation of
      fibroblasts without cytologic features of malignancy. Although desmoid tumors are
      not uncommon, pelvic desmoid tumors are rare and therapeutically challenging. We
      describe the surgical management of seven patients with histologically confirmed
      desmoid tumors arising in the pelvis. STUDY DESIGN: All patients, six with
      primary and one with recurrent desmoid tumors of the female pelvis, were treated
      at Mayo Clinic Rochester between 1976 and 1997. The mean age of one African
      American and six Caucasian patients was 29.8 years (range 17 to 59 years). No
      history of previous relevant pelvic trauma was identified; six patients
      experienced pelvic or leg pain (or both). All patients presented with isolated
      masses; five of seven were located left of the midline, generally involving the
      obturator internis or levator muscles (or both). The surgical approach was
      transabdominal, with a vaginal component in one patient. In addition to this
      retrospective review of these seven patients, literature addressing the
      management of desmoid tumors of the female pelvis is reviewed. RESULTS:
      Extirpative surgery necessitated resection of musculoskeletal, vascular, or
      adjacent soft tissue structures. Mean tumor diameter was 13.9cm (range 5 to 27
      cm). Although the median recorded blood loss was 1,425mL, one patient who refused
      blood products died secondary to surgical hemorrhage. The median followup for the
      remaining evaluable patients was 57 months (range 13 to 249 months). Recurrent
      disease developed in 3 of 6 patients at 3, 11, and 13 months after surgical
      resection and was successfully managed with subsequent reoperations, with or
      without adjuvant radiotherapy. CONCLUSIONS: Although recent reports demonstrate
      selective regression of desmoid tumors with antiestrogen therapy, management of
      symptomatic pelvic desmoid tumors in young women may necessitate an operation. In
      our series, all primary and recurrent tumors were managed with resection of
      involved bone and other adjacent soft tissues. The role of adjunctive
      radiotherapy or hormonal therapy remains to be defined.

PMID- 10945362
TI  - Repeat resection of pulmonary metastases in patients with soft-tissue sarcoma.
AB  - BACKGROUND: Even after an apparent complete resection of sarcomatous pulmonary
      metastases, 40% to 80% of patients will re-recur in the lung. The benefit of
      subsequent re-resection is poorly defined. This study examines patient survival
      after repeat pulmonary exploration for re-recurrent metastatic sarcoma at a
      single institution. STUDY DESIGN: Between July 1982 and December 1997, data on
      3,149 adult in-patients with soft tissue sarcoma were prospectively gathered. Of
      these, pulmonary metastases were present or developed in 719 patients and 248
      underwent at least one resection. Of the patients relapsing in the lung after an
      apparently complete resection, 86 underwent reexploration. Disease-specific
      survival (DSS) after re-resection was the end point of the study. Time to death
      was modeled using the method of Kaplan and Meier. The association of factors to
      time-to-event end points was analyzed using the log-rank test for univariate
      analysis and the Cox proportional hazards model for multivariate analysis.
      Clinicopathologic factors were analyzed with the Pearson chi-square or Fisher's
      exact test when appropriate. RESULTS: The median DSS after re-resection for all
      patients undergoing at least two pulmonary resections was 42.8 months with an
      estimated 5-year survival of 36%. The median DSS in patients with complete
      reresection was 51 months (n = 68) compared with 6 months in patients with an
      incomplete re-resection (n = 16, p<0.0001). Patients with one or two nodules at
      re-resection (n = 39) had a median DSS of 51 months compared with 20 months in
      patients with three or more nodules (n = 40, p = 0.003). Patients in whom the
      largest metastasis re-resected was less than or equal to 2 cm (n = 33) had a
      median DSS of 44 months compared with 20 months in patients with metastasis
      greater than 2 cm (n = 43, p = 0.033). Patients with primary tumor high-grade
      histology (n = 75) had a median DSS of 32 months and patients with low-grade
      histology (n = 11) had a median DSS that was not reached (p = 0.041). Three
      independent prognostic factors associated with poor outcomes may be determined
      preoperatively: > or =3 nodules, largest metastases > 2 cm, and high-grade
      primary tumor histology. Patients with either zero or one poor prognostic factor
      had a median DSS > 65 months and patients with three poor prognostic factors had
      a median DSS of 10 months. CONCLUSIONS: Reexploration for recurrent sarcomatous
      pulmonary metastases appears beneficial for patients who can be completely re
      resected. Outcomes are described by factors that may be determined
      preoperatively, including metastasis size, metastasis number, and primary tumor
      histologic grade. Patients who cannot be completely re-resected or those with
      numerous, large metastasis and high-grade primary tumor pathology have poor
      outcomes and should be considered for investigational therapy.

PMID- 10945363
TI  - Relevance of length of stay reductions.

PMID- 10945364
TI  - Second-time surgery for stage IV sarcoma (a model of sequential metastases)

PMID- 10945365
TI  - Evaluation of the effectiveness of portable low-bandwidth telemedical
      applications for postoperative followup: initial results.
AB  - BACKGROUND: The idea of using telemedical applications to evaluate patients
      remotely is several decades old. It has already been established that x-ray
      images (and magnetic resonance images) can be transferred using a personal
      computer and a modem, and many other such applications have been implemented.
      Over the past 50 years the expense and technical demands of the equipment
      involved in telemedicine have hindered its widespread deployment. The purpose of
      this study is to evaluate the ability of a mobile, low-bandwidth telemedicine
      platform to achieve real-time postoperative visits in the home. STUDY DESIGN:
      This evaluation was designed to evaluate the feasibility of performing a real
      time clinical visit with computer and telecommunications hardware and software. A
      nurse and medical student (for information gathering only) made postoperative
      visits at patients' homes while the physician stayed at the office. Clinical
      evaluations were performed by using low-resolution and frame-rate video, high
      resolution still images, and simultaneous telephony over a standard telephone
      line. These remote visits were followed by a standard visit in the office. Eleven
      patients were included, all of whom had undergone various laparoscopic
      procedures. They lived 5 to 240 miles from their surgeon. Efficiency was measured
      by recording the time required to capture and send data required by the physician
      to make a clinical decision. The time expense was measured at both the patients'
      and physician's locations. Technical issues were evaluated and patient
      satisfaction was assessed by standardized objective questionnaires. The accuracy
      of the evaluation at the remote visit was determined with a standard office
      visit. RESULTS: No technical problems were observed. The mean total time of the
      housecall at the remote site was 86 minutes (range 60 to 160 minutes) and at the
      base station site was 41 minutes (range 21 to 71 minutes). After personnel became
      familiar with the system, the last three visits averaged 61 and 25 minutes at the
      two sites, respectively. This corresponds favorablywith current time requirements
      for visiting nurses and office visits. The patients were highly satisfied with
      the home visit and, on average, rated the experience as 4.8 out of a maximum of
      5. CONCLUSIONS: Followup visits in patients' homes after laparoscopic procedures
      can be accomplished by transmitting simultaneous voice, low-resolution video, and
      high-resolution still images to accurately perform postoperative evaluations over
      standard telephone lines, with time requirements and clinical accuracy similar to
      those of standard visits.

PMID- 10945366
TI  - The last confederate casualty at Gettysburg: a case report and review of similar
      historic cases.

PMID- 10945367
TI  - Cost comparison of electrocardiography versus fluoroscopy for central venous line
      positioning in children.
AB  - BACKGROUND: Although most central venous lines in children are positioned using
      fluoroscopy, electrocardiography (ECG) has been shown to be accurate, and avoids
      unnecessary radiation exposure. We studied whether ECG may also have cost
      advantages. STUDY DESIGN: All ports and Hickman/Broviac catheters placed during a
      2.5-year period were reviewed. Two surgeons routinely used fluoroscopy, and two
      used ECG. Costs included surgeon and anesthesia fees, operating room use, and
      fluoroscopy equipment and personnel. RESULTS: There were 287 cases with
      sufficient data to be included in the study (167 fluoroscopy and 120 ECG). In the
      ECG group, 12 (10%) were converted to fluoroscopy because an adequate tracing
      could not be obtained, but they were kept in the ECG group for data analysis. The
      groups were similar with regard to age, gender, indication, previous catheters,
      and intraoperative or postoperative complications. Time for surgical placement of
      the line was not significantly affected by the positioning technique. Ports
      placed using ECG were less costly than those placed fluoroscopically ($2,880+/
      408 versus $3,595+/-357, p<0.001), and the same was true for tunneled external
      catheters ($2,249 +/- 435 versus $2,923+/-350, p<0.001). CONCLUSIONS: The ECG
      technique was less costly than fluoroscopy, despite a 10% conversion rate. At our
      center, the savings were approximately $700 per procedure. Because operating room
      time used is similar, the additional cost of fluoroscopy can be attributed to the
      need for x-ray equipment and personnel.

PMID- 10945368
TI  - A radical debulking of leiomyomatosis peritonealis disseminata from a colonic
      obstruction: a case report and review of the literature.

PMID- 10945369
TI  - Squamous-cell carcinoma from chronic osteomyelitis.

PMID- 10945370
TI  - Fascio-peritoneal patch repair of the IVC: a workhorse in search of work?

PMID- 10945371
TI  - Prolonged gastrointestinal decompression of the inoperable abdomen: the forgotten
      tube pharyngostomy.

PMID- 10945372
TI  - The value of reporting therapeutic ineffectiveness as an adverse drug reaction.
AB  - Therapeutic ineffectiveness is a frequent drug-related problem that can occur in
      a variety of different situations and be caused by different mechanisms. Examples
      are inappropriate use, interactions or metabolic abnormalities. Observations in
      patients of unexpected ineffectiveness can provide important information with
      regard to such situations. Therefore, ineffectiveness--especially when unexpected
      or unexplained--is a potentially important reportable event in pharmacovigilance.
      The terms regarding ineffectiveness in the WHO Adverse Reaction Terminology
      (WHOART) have been recently revised in order to enable optimal coding of such
      case reports.

PMID- 10945373
TI  - Post-transplant malignancy: the role of immunosuppression.
AB  - Immunosuppressed organ allograft recipients have a 3- to 4-fold increased risk of
      developing tumours, but the risk of developing certain cancers is increased
      several hundredfold. With the exception of skin and lip cancers, most of the
      common malignancies seen in the general population are not increased in
      incidence. Instead, there is a higher frequency of some relatively rare tumours,
      including post-transplant lymphomas and lymphoproliferative disorders (PTLD),
      Kaposi's sarcoma (KS), renal carcinomas, in situ carcinomas of the uterine
      cervix, hepatobiliary carcinomas, anogenital carcinomas and various sarcomas
      (excluding KS). Skin and lip cancers present some unusual features: a remarkable
      frequency of KS, reversal of the ratio of basal to squamous cell carcinomas seen
      in the general population, the young age of the patients, and the high incidence
      of multiple tumours (in 43% of the patients). Anogenital cancers occur at a much
      younger age than in the general population. Salient features of PTLD are the high
      frequency of Epstein-Barr virus-related lesions, frequent involvement of
      extranodal sites, a marked predilection for the brain and frequent allograft
      involvement. As the immunosuppressed state per se and various potentially
      oncogenic viruses play a major role in causing these cancers, preventative
      measures include reducing immunosuppression to the lowest level compatible with
      good allograft function and prophylactic measures against certain virus
      infections. Reduction of exposure to sunlight may also decrease the incidence of
      skin cancer. In addition to conventional treatments (resection, radiation
      therapy, chemotherapy) patients may receive antiviral drugs, interferon-alpha and
      various other manipulations of the immune system. A significant percentage of
      cases of PTLD and KS respond to reduction or cessation of immunosuppressive
      therapy.

PMID- 10945374
TI  - A risk-benefit assessment of injections of hyaluronan and its derivatives in the
      treatment of osteoarthritis of the knee.
AB  - Hyaluronan is critical for the homeostasis of the joint as an organ, in part,
      because it provides the rheological properties (viscosity and elasticity) of the
      synovial fluid. These properties depend upon both the concentration and the
      molecular weight of the hyaluronan in the synovial fluid. In osteoarthritis, the
      hyaluronan is both smaller in size and lower in concentration. Thus, it is
      rational and physiologically meaningful to treat osteoarthritis with
      viscosupplementation, i.e. injection of material designed to increase the
      rheological properties of the synovial fluid. It is important, though, to assess
      the risks and benefits of such a physiological treatment. There are various
      products on the market for viscosupplementation. These include hyaluronan
      preparations of relatively low molecular weight (Hyalgan and ARTZ), a hyaluronan
      preparation of intermediate molecular weight, but still lower molecular weight
      than that of the hyaluronan in normal healthy synovial fluid (Orthovisc), and a
      cross-linked hyaluronan (a hylan) of high molecular weight (Synvisc). The
      evidence from in vitro and in vivo models of osteoarthritis and from clinical
      trials to date suggests that efficacy, as would be expected by mechanistic
      reasoning, depends strongly upon molecular weight. The available evidence
      indicates that these products differ little in the incidence and severity of
      adverse events (about 2 to 4%, almost always local swelling, and with no adverse
      sequelae). All are very well tolerated in comparison to nonsteroidal anti
      inflammatory drug therapy, although direct comparisons are few. The only
      potentially serious adverse event is joint infection, which is rare and directly
      dependent upon the number of injections, among other factors. No infection has
      been related to contamination of any of the products. In summary, treatment with
      low molecular weight preparations of hyaluronan seems to be effective. However,
      viscosupplementation with hyaluronan preparations may have slightly higher risk
      and less benefit than viscosupplementation with hylans, because the relatively
      lower molecular weight hyaluronan preparations require more injections which may
      incur higher costs and theoretically an increased chance of infection.
      Viscosupplementation with hylans is clearly effective, and the available evidence
      suggests that the benefits almost certainly outweigh the risks.

PMID- 10945375
TI  - A risk-benefit evaluation of aciclovir for the treatment and prophylaxis of
      herpes simplex virus infections.
AB  - The objective of this article is to review and evaluate risks and benefits
      associated with the use of acyclovir in the treatment and prophylaxis of common
      manifestations of herpes simplex virus (HSV) infections in immunocompetent and
      immunocompromised patients. Information was found through a MEDLINE search using
      keywords: herpes simplex virus, genital herpes, herpes labialis, acyclovir and
      acyclovir. Selected articles were randomised, double-blind, placebo-controlled,
      clinical trials. 30 such trials involving 3364 persons were evaluated. All
      articles were reviewed by the authors and the data were extracted and summarised.
      In both immunocompetent and immunocompromised hosts, acyclovir therapy
      demonstrated a high degree of clinical efficacy. None of the studies reported
      statistically significant differences between acyclovir and placebo for mild or
      major adverse events. This evaluation found that acyclovir is both effective and
      well tolerated for treatment and prophylaxis of genital, oral and mucocutaneous
      HSV infections in immunocompetent and immunocompromised patients. In most
      clinical scenarios. the benefit of acyclovir exceeded any risks by a comfortable
      margin. The availability of acyclovir as a generic preparation further improves
      the benefit to cost ratio.

PMID- 10945377
TI  - A survey on factors that could affect adverse drug reaction reporting according
      to hospital pharmacists in Great Britain.
AB  - INTRODUCTION: Since April 1997, UK hospital pharmacists have been invited to
      submit reports of suspected adverse drug reactions (ADRs) to the Committee on
      Safety of Medicines (CSM) and Medicines Control Agency. Three studies have
      investigated the involvement of hospital pharmacists in ADR reporting; however,
      they did not investigate the possible factors that could affect ADR reporting.
      OBJECTIVES: (i) To analyse the extent to which hospital pharmacists think that
      specified factors could affect reporting ADRs; (ii) to identify any additional
      factors that could hinder reporting; and (iii) to recommend possible methods to
      improve reporting. METHODS: Piloted questionnaires were sent to 548 hospital
      pharmacists in Great Britain randomly selected by the Royal Pharmaceutical
      Society of Great Britain (RPSGB) from their computer database. 346 questionnaires
      were returned and 280 were included in this study. RESULTS: 46% of the
      pharmacists had identified ADRs that were considered to be reportable according
      to the CSM criteria in the 6 months prior to the survey. 39% did not report these
      ADRs either to the CSM or the manufacturers. Only 8.2% reported that their
      hospitals had a written policy; conversely, 73.7% agreed that such a policy could
      enhance ADR reporting. Although not statistically significant, the result showed
      an increasing tendency to report ADRs by pharmacists who had received training.
      Furthermore, there was an increasing tendency to report ADRs with increasing
      seniority. DISCUSSION: The results show that hospital pharmacists say they are
      more likely to report serious and rare ADRs and ADRs associated with newly
      marketed drugs. Factors that could reduce ADR reporting included being busy at
      work, lack of confidence in recognising ADRs and the fear of breaching patient
      confidentiality. Most common suggestions on methods to improve ADR reporting were
      to provide ADR training and meetings (34%) and a hospital written policy (24%).
      RECOMMENDATIONS: ADR training and meetings would be a useful step in improving
      hospital pharmacist ADR reporting. Therefore, we recommend that the CSM and the
      RPSGB liaise with regional drug information centres and schools of pharmacy to
      provide more study days and training programmes for hospital pharmacists.
      Furthermore, the CSM should write to the 'Drugs and Therapeutics Committee' of
      each hospital and encourage them to develop a written local policy for pharmacist
      ADR reporting. Further studies should be conducted to test the recommendations
      noted here, assessing the response of the pharmacists in terms of absolute
      numbers of reports made. It would be particularly interesting to study the need
      for a written hospital policy and education.

PMID- 10945378
TI  - Respiratory mechanics in ARDS: a siren for physicians?

PMID- 10945379
TI  - Antithrombin in severe sepsis--"new" indication of an "old" drug?

PMID- 10945380
TI  - How continuous are continuous drug infusions?

PMID- 10945381
TI  - Cerebral microdialysis as a new tool for neurometabolic monitoring.

PMID- 10945382
TI  - Evaluation of a new module in the continuous monitoring of respiratory mechanics.
AB  - OBJECTIVE: Bedside monitoring of respiratory mechanics facilitates the use of
      lung protective ventilation in acute lung injury (ALI). We evaluated a new
      clinical monitor of respiratory mechanics. DESIGN: Prospective, in vitro and in
      vivo study. SETTING: University hospital. PATIENTS: Measurements were done using
      a lung model and in patients after cardiac surgery (n = 10) and in patients with
      ALI (n = 10). INTERVENTIONS AND MEASUREMENTS: The monitor provides continuous
      monitoring of pressure, flow and volume waveform and loop data, and automatically
      collected variables of respiratory mechanics. Breath-by-breath respiratory
      mechanics data and the automated variables obtained with the new monitor were
      compared with flow and pressure reference data. RESULTS: Waveform data comparison
      showed errors of less than 5% for most variables. Automatically recorded
      respiratory pressures and volumes showed good agreement within clinical standards
      when compared to reference (errors from 2.5% to 6.2%). Automatically recorded
      derived variables present poor agreement (errors from 8.1% to 158.3%).
      CONCLUSIONS: The waveform data of the new monitor is accurate. The value of the
      automatically derived variables is limited by the fact that inspiratory plateau
      pressure and plateau compliance have no direct physiological meaning.
      Nevertheless, in clinical monitoring much information can be derived from the
      waveform signals alone and from pressure-volume and flow-volume loops. These
      facilitate monitoring changes in respiratory mechanics in the ALI patient.

PMID- 10945376
TI  - Drug-induced respiratory disorders: incidence, prevention and management.
AB  - Various drugs are associated with adverse respiratory disorders (ARDs) ranging in
      severity from mild, moderate to severe and even fatal. Cardioselective and
      nonselective beta-blockers, calcium antagonists and dipyridamole can induce
      asthma. ACE inhibitors are mainly associated with cough. Amiodarone is related to
      a form of interstitial pneumonitis (IP) which can be fatal, tocainidine and
      flecainidine to a form of IP, and hydrochlorothiazide to a form of IP and
      pulmonary oedema. Antiasthmatic drugs can be associated with a paradoxical
      bronchospasm, while leukotriene antagonists are linked to the development of
      Churg-Strauss syndrome. Nonsteroidal anti-inflammatory drugs including aspirin
      (acetylsalicylic acid) may induce asthma. Gold is mainly related to IP,
      penicillamine to IP, systemic lupus erythematosus, bronchiolitis obliterans, and
      Goodpasture's syndrome. Acute respiratory reactions to nitrofurantoin include
      dyspnoea, cough, IP, and pleural effusion while IP and fibrosis are common in
      chronic reactions. Other antibacterials mainly evoke pneumonitis, pulmonary
      infiltrates and eosinophilia, and bronchiolitis obliterans. ARDs are similar for
      most categories of cytotoxic agents, with chronic pneumonitis and fibrosis being
      the most common. Noncardiogenic pulmonary oedema occurs as the most common
      respiratory complication in opioid agonist addiction. Psychotropic drugs such as
      phenothiazides, butyrophenones and tricyclic antidepressants can also induce
      pulmonary oedema. Oral contraceptives may produce asthma exacerbation, while long
      term use and/or high doses of postmenopausal hormone replacement therapy increase
      the risk of asthma. Bromocriptine is mainly associated with pleural effusion,
      while methysergide is usually associated with pleural effusion and fibrosis. Some
      anorectic agents have been linked to the development of primary pulmonary
      hypertension. The possibility of the occurrence of ARDs should be taken into
      account in each individual patient. Although in most cases the adverse effects
      are unpredictable, they can be reduced to a minimum or prevented if some drugs
      are avoided or stopped in time.

PMID- 10945383
TI  - The effect of lung injury and excessive lung fluid, on impedance cardiac output
      measurements, in the critically ill.
AB  - OBJECTIVES: To investigate the relationship between the attenuation of impedance
      cardiac output (IC(co)) measurements and lung fluid content in critically ill
      patients. DESIGN: Observational study. SETTING: Intensive Care Unit of a major
      teaching hospital in Hong Kong. PATIENTS: Twenty-four critically ill patients who
      required a pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Triplicate
      thermodilution cardiac output (TD(co)) and BoMed NCCOM3 (IC(co)) measurements
      were made simultaneously on a single occasion in each patient. Lung fluid
      accumulation was assessed by: (a) thoracic impedance (Zo), (b) radiological
      assessment of chest X-rays using an alveolar consolidation score (0-4) and (c)
      scoring the degree of hypoxia and use of positive end-expiratory pressure (PEEP).
      Offsets (TD(co)-IC(co))/TD(co), expressed as percentage, were compared with these
      indices of excess lung fluid. Patients were divided into those with sepsis (n =
      13), fluid balance problems (n = 5) and cardiothoracic problems (n = 6). Mean
      cardiac output values were: 6.7 l/min TD(co) (range 3.6-12.9) and 5.2 l/min
      IC(co) (range 2.7-9.0). Overall the TD(co) and IC(co) values showed great
      variance, with a bias and limits of agreement of 1.49 +/- 4.16 l/min, or +/- 69%.
      In septic patients, increasing offset was correlated with decreases in Zo (r =
      0.73, P = 0.005) and increases in alveolar consolidation score (r = 0.72, P =
      0.005). CONCLUSIONS: The BoMed under-estimates cardiac output in critically ill
      patients. In septic patients the degree of attenuation of IC(co) can be related
      to the extent of lung injury and fluid accumulation within the thorax.

PMID- 10945384
TI  - Cardiac function after intermittent antegrade warm blood cardioplegia:
      contribution of the double-indicator dilution technique.
AB  - OBJECTIVE: To evaluate cardiac performance following coronary artery surgery
      using two different techniques of cardioplegia. DESIGN: Randomized prospective
      study. SETTING: Adult cardiothoracic intensive care unit in a university
      hospital. STUDY POPULATION: Thirty patients undergoing isolated coronary surgery.
      INTERVENTIONS: Patients were randomized to receive either intermittent antegrade
      warm blood cardioplegia with normothermic bypass (group 1) or combined antegrade
      and retrograde cold crystalloid cardioplegia with hypothermic bypass (group 2).
      Hemodynamic evaluation included conventional measurements from a pulmonary artery
      catheter and data obtained by thermal dye dilution utilizing an arterial
      thermistor-tipped fiberoptic catheter. RESULTS: The only major difference between
      groups was a significantly higher right atrial pressure in group 2, from 4 h to
      24 h after surgery (8.8 +/- 2.6 vs. 11.8 +/- 3.2 mmHg at 4 h and 11 +/- 3.1 vs.
      8.5 +/- 1.8 mmHg at 24 h, P = 0.04). After cold cardioplegia a significant
      increase in right atrial pressure was observed (7.5 +/- 3.1 before surgery vs.
      11.4 +/- 3 mmHg at 8 h, P = 0.003) whereas right ventricular end diastolic volume
      index did not increase significantly, suggesting impaired right ventricular
      diastolic compliance in this group. CONCLUSIONS: Until 24 h after surgery cold
      cardioplegia is associated with impaired right ventricular filling, which seems
      better preserved by intermittent antegrade warm blood cardioplegia. End-diastolic
      volume measurement with the double-indicator technique allows differentiation
      between systolic and diastolic dysfunction.

PMID- 10945385
TI  - CO assessment by suprasternal Doppler in critically ill patients: comparison with
      thermodilution.
AB  - OBJECTIVE: Comparison of suprasternal Doppler (SST) and thermodilution (TD) for
      the measurement of cardiac output (CO) in critically ill patients. DESIGN:
      Prospective study. SETTING: Intensive care unit of a university hospital.
      PATIENTS AND PARTICIPANTS: 65 consecutive critically ill patients requiring a
      pulmonary artery catheter. INTERVENTIONS: Paired CO measurements were made
      simultaneously using SST and TD by two independent operators. The time to obtain
      a CO value by SST was measured. Correlation coefficients and the linear
      regression equation were determined. A Bland and Altman diagram was plotted. A
      Bland and Altman diagram was also plotted for the level of cardiac index (CI)
      values (low: CI < 2.5 l min(-1) m(-2); normal: 2.5 < or = CI < or = 4.5 l min(-1)
      m(-2); high: CI > 4.5 l min(-1) m(-2)). MEASUREMENTS AND RESULTS: In seven
      patients SST failed to measure CO. In the remaining 58 patients 314 paired CO
      measurements were performed. The mean time to measure CO by SST was 73 +/- 45 s.
      The equation of linear regression was: SST(CO) = 0.84 TD(CO) + 1.39. The
      correlation coefficient was 0.84. The bias between SST and TD was -0.2 +/- 1.4 l
      min(-1). Biases were -0.23 +/- 0.50, -0.20 +/- 0.68, and 0.25 +/- 0.92 l min(-1)
      m(-2) for low, normal, and high levels of CI, respectively. CONCLUSION: SST does
      not accurately measure CO but allows a rapid assessment of CI level in critically
      ill patients.

PMID- 10945386
TI  - Failure of a brief educational program to improve interpretation of pulmonary
      artery occlusion pressure tracings.
AB  - OBJECTIVE: To determine whether a brief educational program can reduce
      variability of interpretation of pulmonary artery occlusion pressure (PAOP)
      tracings. DESIGN: Prospective, observational study. PARTICIPANTS: Twenty-three
      intensive care nurses and 18 physicians. INTERVENTIONS: Participants interpreted
      PAOP tracings before and 1 week after receiving a single, brief educational
      session and/or written materials ("in-service") designed to reduce interobserver
      variability of PAOP interpretation. Differences between two reference values
      before and after in-service (mean population and Chief of Critical Care's
      readings) were compared for both groups. RESULTS: There were no significant
      differences in the variabilities in PAOP interpretations before and after in
      service in either group. CONCLUSIONS: We conclude that this specific educational
      program was ineffective in reducing variability of interpretation of PAOP
      tracings. These data suggest that more comprehensive educational tools and/or
      sustained programs may be required to improve performance of critical care
      personnel in PAOP interpretation.

PMID- 10945387
TI  - Antithrombin III in patients with severe sepsis: a pharmacokinetic study.
AB  - OBJECTIVES: To evaluate the safety, pharmacokinetics, and the practicability of
      two different antithrombin III (AT III) high-dose regimens in patients with
      severe sepsis. DESIGN: Prospective, open, randomized, 2 parallel groups,
      multinational clinical trial. SETTING: Eleven academic medical center intensive
      care units (ICU) in Austria, Belgium, Denmark, Germany, Norway and Sweden.
      PATIENTS: Thirty-three patients with severe sepsis who received standard
      supportive care and antimicrobial therapy, in addition to the administration of
      AT III. INTERVENTIONS: Patients received an intravenous loading dose of 6,000 IU
      AT III followed by either intermittent bolus infusions of 1,000 IU AT III every 4
      h or a continuous infusion of 250 IU AT III/h for 4 days, resulting in a total
      dose for both dosage regimens of 30,000 IU AT III. MEASUREMENTS: All patients
      were evaluated for safety and all but one for pharmacokinetics. RESULTS AND
      CONCLUSIONS: The administration of AT III was safe and well tolerated. The
      overall 28-day all-cause mortality was 30% (43% intermittent bolus infusions; 21%
      continuous infusion). The mean probability of dying according to the SAPS II was
      48%. The difference in mortality between both groups was within the range of
      chance. AT III plasma levels were elevated from low baseline levels to above 120%
      soon after onset of AT III therapy and remained at these levels for the treatment
      phase of 4 days. Functional and immunologic levels of AT III corresponded very
      well. With an overall median volume of distribution of 4.5 l (range: 2.4-6.5 l),
      AT III only moderately extended beyond plasma. The overall median elimination
      half-life was 18.6 h (range: 5.1-37.4). Overall, median response was 1.75% per
      IU/kg (range: 1.14-2.8). The variability of elimination parameters was quite
      noteworthy (CV = 41-59%), whereas distribution-related parameters showed a
      moderate variability (CV = 24%). In spite of this variability, both high-dose IV
      regimens reliably provided AT III levels above 120% for all but one patient. An
      increased mortality was observed for patients with a distribution volume
      exceeding 4.5 l (or a response < 1.7% per IU/kg). AT III distribution volumes
      above 4.5 l might indicate a capillary leak phenomenon. The continuous infusion
      regimen was slightly preferred by the investigators with regard to
      practicability.

PMID- 10945388
TI  - Hypothermia and cytokines in septic shock. Norasept II Study Investigators. North
      American study of the safety and efficacy of murine monoclonal antibody to tumor
      necrosis factor for the treatment of septic shock.
AB  - BACKGROUND: Hypothermic patients with sepsis have been reported to have a higher
      mortality than febrile septic patients. The failure to mount a febrile response
      in sepsis is poorly understood. Since the proinflammatory cytokines play a
      crucial role in the genesis of fever, we postulated that hypothermic patients
      with sepsis would have lower circulating levels of these cytokines than febrile
      patients. METHODS: Patients with septic shock who were enrolled into the placebo
      limb of the North American study of the safety and efficacy of murine monoclonal
      antibody to tumor necrosis factor for the treatment of septic shock (NORASEPT II)
      were analyzed. Body temperature, interleukin-6, tumor necrosis factor alpha,
      soluble tumor necrosis factor receptor-55, and soluble tumor necrosis factor
      receptor-75 concentrations were measured at enrollment. The study population was
      divided into a hypothermic (temperature < 35.6 degrees C) and a febrile group
      (temperature > or = 38.3 degrees C) according to the core temperature at
      enrollment (normothermia was an exclusion criteria). Clinical, demographic, and
      cytokine data were extracted, allowing for comparisons between these two groups
      of patients. In addition, the correlation between the core body temperature and
      cytokine levels at enrollment was determined. RESULTS: A complete data set was
      available for 930 patients; 195 patients (21%) were hypothermic at enrollment.
      The 28-day survival of these patients was significantly lower than that of the
      febrile patients (34% vs. 59%, p < 0.001). Hypothermia (and enrollment
      temperature) were independent predictors of mortality. The hypothermic patients
      had a higher incidence of organ dysfunction at enrollment than the febrile
      patients. There was no significant difference in the cytokine profile between the
      two groups of patients. In addition, there was no correlation between the core
      body temperature at enrollment and the circulating levels of cytokines measured.
      CONCLUSION: Hypothermic patients with septic shock have a significantly higher
      mortality with a higher incidence of organ dysfunction than febrile septic shock
      patients. The hypothermia in these patients cannot be explained by lower levels
      of circulating proinflammatory cytokines.

PMID- 10945389
TI  - Relationship between intracranial pressure, mild hypothermia and temperature
      corrected PaCO2 in patients with traumatic brain injury.
AB  - OBJECTIVE: To study the effects of mild hypothermia and associated changes in
      temperature-corrected PaCO2 (cPaCO2) on intracranial pressure (ICP), mean
      velocity of the middle cerebral artery (Vm), and venous jugular saturation in O2
      (SjvO2) in patients with severe traumatic brain injury (TBI). DESIGN:
      Prospective, observational study. SETTING: Intensive care unit. PATIENTS: Severe
      TBI patients mechanically ventilated, sedated and paralyzed. INTERVENTIONS:
      Twenty patients were subjected to four consecutive periods: (a) normocapnia
      normothermia; (b) hypocapnia-normothermia, where hypocapnia was induced by an
      increase in minute volume; (c) hypocapnia-hypothermia, where hypocapnia was
      induced by hypothermia maintaining the ventilatory settings constant; (d)
      normocapnia-hypothermia, where normocapnia was achieved by a decrease in minute
      volume. MEASUREMENTS AND RESULTS: cPaCO2 was 41 +/- 8 mmHg in periods 1 and 4,
      and 31 +/- 7 mmHg in periods 2 and 3. Core temperature was 37.1 +/- 0.8 degrees C
      in periods 1 and 2, and 34.1 +/- 1.1 degrees C in periods 3 and 4. End-tidal CO2
      and cPaCO2 values showed no difference between periods 1 and 4 and periods 2 and
      3. ICP and Vm were dependent on cPaCO2 but independent of core temperature
      values. SjvO2 was related to cPaCO2 and was significantly higher during period 3
      than during period 2 (P < 0.05). CONCLUSION: The decrease in ICP was similar when
      hypocapnia was induced by hyperventilation or as a result of hypothermia alone.
      The relationship between cPaCO2 and ICP might predict variations in ICP during
      changes in core temperature. Further studies are needed to confirm the cerebral
      metabolic effects of moderate hypothermia in TBI patients.

PMID- 10945390
TI  - Cerebral CO2 vasoreactivity evaluation by transcranial Doppler ultrasound
      technique: a standardized methodology.
AB  - OBJECTIVE: In normal subjects cerebral CO2 vasoreactivity is measured during
      spontaneous hyperventilation, breathholding, or adding CO2 to inspiratory gases.
      The correlation between CO2 and cerebral blood flow may, however, be invalidated
      by the effects of a modified respiratory pattern on venous return, sympathovagal
      balance, and cathecolamine release. Moreover, the duration of the test, usually
      not considered, may play an important role. This may justify the scattering of
      values found in literature. We evaluated a new standardized method for overcoming
      these confounding factors. DESIGN: Experimental. PARTICIPANTS: Twenty-one healthy
      volunteers. METHODS: Subjects were connected through a mouthpiece to a mechanical
      ventilator set in the intermittent positive pressure ventilation mode. The
      ventilator was fed by two 40-1 tanks, one of which contained 5% CO2. The
      inspiratory CO2 concentration was varied at fixed time intervals from 0% to 5%
      without modifying ventilator settings. End-tidal CO2 was measured at the
      mouthpiece. Mean blood velocity (V(m)) and pulsatility index (PI) in the middle
      cerebral artery were measured by means of transcranial Doppler ultrasound.
      RESULTS: The test was easily applicable and well tolerated. No hemodynamic
      alterations were observed during the tests. The correlation between CO2 and V(m)
      was always linear and highly significant (R2 > 0.8, p < 0.0001). A low
      intersubject variability was observed. No difference was found between the two
      hemispheres, nor between the sexes. CONCLUSIONS: The strict standardization of
      the technique, avoiding hemodynamic interference, may explain the low
      intersubject variability. The value of this technique in ventilated neurosurgical
      patients is still speculative, but it might allow the collecting of valuable data
      together with a reduction in exposure to CO2, and hence cerebral blood flow
      modifications.

PMID- 10945391
TI  - Intestinal elimination of hydroxyethyl starch?
AB  - OBJECTIVE: Hydroxyethyl starch (HES) is mainly eliminated via the kidneys. Any
      information about extrarenal elimination obtained so far has been either
      incomplete or contradictory. The objective of this study was to quantify the
      intestinal excretion of infused HES with a mean molecular weight of 200,000 and a
      molar substitution of 0.5 (HES 200/0.5) and to compare the reappearance/recovery
      rate in urine and plasma. DESIGN: Prospective clinical study without control
      group. SETTING: The study was conducted at the Institute of Hypertension of the
      Society of Clinical Pharmacology, Vienna, Austria, which is an establishment for
      research in volunteers. PARTICIPANTS: The results of six out of seven healthy
      male volunteers were appropriate for analysis. One trial subject had to be
      excluded from the study because of severe protocol violation (mixing of stool and
      urine samples). INTERVENTIONS AND METHODS: Each volunteer was administered 500 ml
      of 10% HES 200/0.5 in a 0.9% NaCl solution intravenously within 1 h. A gut lavage
      with 6 l of a polysaccharide free solution was continuously administered from 3 h
      prior to until 2 h after the HES infusion to facilitate the collection of the
      samples and to exclude any source of error at analysis. HES was quantified with
      the hexokinase method. MEASUREMENTS AND RESULTS: Right from the beginning of the
      infusion until 10 h after its completion, the cumulative HES excretion with feces
      (principle parameter) and urine as well as selective plasma volume and HES plasma
      level were measured. Six and 14 h after the infusion had been completed, the
      recovery rates of HES in urine were about 30% and 40%, respectively, and in
      plasma about 23% and 8%, respectively. By contrast, not more than a kind of
      "background noise amount" of HES (about 0.2 %) could be recovered in feces ( mean
      value in % of the infused amount of the substance). Six and 14 h after the
      infusion had been completed, the total recovery rates of HES were 53% and 49%,
      respectively. CONCLUSION: In a physiologically unimpaired gut HES 200/0.5 is not,
      or only to an infinitesimal extent, eliminated via the intestine. The question if
      there is any alternative path to renal excretion for HES still remains to be
      answered. As the calculated reappearance/recovery rate of HES is only about 50 %
      of the administered dose, further investigations as to the final fate of HES
      appear necessary.

PMID- 10945392
TI  - Comparison of a specialist retrieval team with current United Kingdom practice
      for the transport of critically ill patients.
AB  - OBJECTIVE: The inter-hospital transfer of critically ill patients in the United
      Kingdom is commonly undertaken using standard ambulance under junior doctor
      escort, despite recommendations for the use of specialist retrieval teams.
      Patients are transferred into University College London Hospitals (UCLH)
      intensive care unit (ICU) by both methods. We undertook to evaluate the effect of
      transfer method on acute physiology (within 2 h of ICU admission) and early
      mortality ( < 12 h after ICU admission). DESIGN: Retrospective review of all
      transfers over 1 year. SETTING: UCLH ICU. SUBJECTS: 259 transfers; 168 by
      specialist retrieval team (group A) and 91 by standard ambulance with doctor
      provided by referring hospital (group B). INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Acute physiology (pH, PaO2, PaCO2, heart rate (HR), mean arterial blood
      pressure (MAP), 24 h severity of illness scores (APACHE II, SAPS II), length of
      stay and mortality. RESULTS: There were no differences in demographic
      characteristics or severity of illness between the two groups; nevertheless
      significantly more patients in group B than in group A were severely acidotic (pH
      < 7.1: 11% vs. 3%, p < 0.008) and hypotensive (MAP < 60: 18 % vs. 9%, p < 0.03)
      upon arrival. In addition, there were more deaths within the first 12 h after
      admission with 7.7 % deaths (7/91) in group B transfers vs. 3% (5/168) in group
      A. CONCLUSIONS: The use of a specialist transfer team may significantly improve
      the acute physiology of critically ill patients and may reduce early mortality in
      ICU.

PMID- 10945393
TI  - Lung recruitment and lung volume maintenance: a strategy for improving
      oxygenation and preventing lung injury during both conventional mechanical
      ventilation and high-frequency oscillation.
AB  - OBJECTIVE: To determine whether using a small tidal volume (5 ml/kg) ventilation
      following sustained inflation with positive endexpiratory pressure (PEEP) set
      above the critical closing pressure (CCP) allows oxygenation equally well and
      induces as little lung damage as high-frequency oscillation following sustained
      inflation with a continuous distending pressure (CDP) slightly above the CCP of
      the lung. MATERIAL AND METHODS: Twelve surfactant-depleted adult New Zealand
      rabbits were ventilated for 4 h after being randomly assigned to one of two
      groups: group 1, conventional mechanical ventilation, tidal volume 5 ml/kg,
      sustained inflation followed by PEEP > CCP; group 2, high-frequency oscillation,
      sustained inflation followed by CDP > CCP. RESULTS: In both groups oxygenation
      improved substantially after sustained inflation (P < 0.05) and remained stable
      over 4 h of ventilation without any differences between the groups.
      Histologically, both groups showed only little airway injury to bronchioles,
      alveolar ducts, and alveolar airspace, with no difference between the two groups.
      Myeloperoxidase content in homogenized lung tissue, as a marker of leukocyte
      infiltration, was equivalent in the two groups. CONCLUSIONS: We conclude that a
      volume recruitment strategy during small tidal volume ventilation and maintaining
      lung volumes above lung closing is as protective as that of high-frequency
      oscillation at similar lung volumes in this model of lung injury

PMID- 10945394
TI  - Distribution of pulmonary blood flow in the perfluorocarbon-filled lung.
AB  - OBJECTIVE: Partial liquid ventilation (PLV) improves gas exchange in animal
      studies of lung injury. Perfluorocarbons (PFCs) are heavy liquids and are
      therefore preferentially delivered to the most dependent areas of lung. We
      hypothesised that improved oxygenation during PLV might be the consequence of a
      redistribution of pulmonary blood flow away from poorly ventilated, dependent
      alveoli, leading to improved ventilation/perfusion (V/Q) matching. This study
      investigated whether partially filling the lung with PFC would result in a
      redistribution of pulmonary blood flow. DESIGN: Prospective experimental study.
      SETTING: Hospital research institute laboratory. PARTICIPANTS: Six anaesthetised
      pigs without lung injury. INTERVENTIONS: Animals were anaesthetised and
      ventilated (gas tidal volume 12 ml/kg, PEEP 5, FIO2 1.0, rate 16). Whilst the
      pigs were maintained in the supine position, regional pulmonary blood flow was
      measured during conventional gas ventilation and repeated during PLV. Flow to
      regions of lung was determined by injection of radioactive microspheres (Co(57),
      Sn(113), Sc(46)). Measurements were performed with ventilation held at end
      expiratory pressure and, in two PLV animals only, repeated with ventilation held
      at peak inspiratory pressure. RESULTS: During conventional gas ventilation, blood
      flow followed a linear distribution with the highest flow to the most dependent
      lung. In the lung partially filled with PFC a diversion of blood flow away from
      the most dependent lung was seen (p = 0.007), resulting in a more uniform
      distribution of flow down the lung (p = 0.006). Linear regression analysis (r2 =
      0.75) also confirmed a difference in distribution pattern. On applying an
      inspiratory hold to the liquid-containing lung, blood flow was redistributed back
      towards the dependent lung. CONCLUSIONS: Partially filling the lung with PFC
      results in a redistribution of pulmonary blood flow away from the dependent
      region of the lung. During PLV a different blood flow distribution may be seen
      between inspiration and expiration. The clinical significance of these findings
      has yet to be determined.

PMID- 10945395
TI  - Inhaled nitric oxide during partial liquid ventilation shifts pulmonary blood
      flow to the non-dependent lung regions.
AB  - OBJECTIVE: To elucidate the change in pulmonary blood flow brought about by
      nitric oxide (NO) inhalation during partial liquid ventilation (PLV). DESIGN:
      Prospective, controlled study. SETTING: A research laboratory at a university
      medical center. SUBJECTS: Fourteen Japanese white rabbits (3.2 +/- 0.05 kg body
      weight). INTERVENTIONS: Animals were mechanically ventilated in the right
      decubitus position. Following saline lung lavage, PLV was started with perflubron
      (15 ml/kg). In the NO group (n = 7), PLV was supplemented by a 30-min challenge
      of NO inhalation (10 ppm) from 30 min after the initiation of PLV. In the control
      group (n = 7), PLV was continued for 60 min. MEASUREMENTS AND MAIN RESULTS: For
      the pulmonary blood flow analysis, colored microspheres were administered from
      the right atrium at 30 min (T(PLV1)) and 60 min (T(PLV2)) after the initiation of
      PLV. The percentage of the left lung blood flow in the total pulmonary blood flow
      (%Q(L)/Q(T)) was significantly increased by NO inhalation in the NO group (p =
      0.0164), while that in the control group was significantly decreased during the
      same period (p = 0.0107). PaO2 in the NO group was significantly increased by NO
      inhalation (p = 0.0153), but not in the control group (p = 0.7911). CONCLUSION:
      Inhaled NO during PLV shifted the pulmonary blood flow to the non-dependent
      region and improved pulmonary gas exchange. This result suggested that inhaled NO
      took effect predominantly in the non-dependent region during PLV.

PMID- 10945396
TI  - The effect of CVVHD and endotoxin on the oxidative burst, adhesion molecules and
      distribution in tissues of granulocytes.
AB  - OBJECTIVE: Extracorporeal circulation, such as cardiopulmonary bypass and
      haemodialysis, has been associated with an activation of the immune system,
      especially the granulocytes. Continuous veno-venous haemodiafiltration (CVVHD) is
      used in critically ill septic patients. During CVVHD cytokines are excreted in
      the ultrafiltrate. But when the membranes used in CVVHD are cultured with
      granulocytes, the granulocytes are slightly activated. This effect is potentiated
      by endotoxin. We therefore, in vivo, compared the effect on granulocyte
      activation of CVVHD with an endotoxin group and a control group. METHODS: Thirty
      one pigs were anaesthetized and mechanically ventilated. In ten pigs CVVHD was
      performed. Eleven pigs received an infusion of Escherichia coli endotoxin 30
      mu/kg(-1) and ten pigs served as a control group. The adhesion molecules CD18 and
      CD62L were measured using monoclonal antibodies. The oxidative burst activity was
      assayed as superoxide dismutase-inhibitory reduction of cytochrome c. The number
      of granulocytes in peripheral blood and in the lungs and liver were counted.
      RESULTS: The infusion of endotoxin was followed by granulocytopenia, reduced
      oxidative burst activity, increased expression of CD18 and decreased expression
      of CD62L on granulocytes. Accumulation of granulocytes in liver and lung tissue
      was also noted in this group. CVVHD was only associated with a non-significant
      decrease in CD62L expression on granulocytes. It did not affect any of the other
      measured immunological parameters. CONCLUSION: In contrast to endotoxin-induced
      sepsis, the granulocytes were not activated during CVVHD.

PMID- 10945397
TI  - Influence of infusion line compliance on drug delivery rate during acute line
      loop formation.
AB  - OBJECTIVE: To determine whether infusion line compliance contributes to irregular
      drug delivery during vertical displacement of syringe pumps. DESIGN: Five
      different commercially available infusion lines were studied at infusion rates of
      0.5, 1.0, and 1.5 ml/h. Zero drug delivery time was measured after acute line
      loop formation (70 cm) using an electronic balance. Compliance of each infusion
      line was calculated using a pressure transducer and measurement of the occlusion
      release bolus at 300 mmHg occlusion pressure. Finally, the influence of infusion
      line compliance on drug delivery during acute lowering of the syringe pump was
      studied using low- and high-compliance infusion lines. RESULTS: Acute line loop
      formation resulted in zero drug delivery time from 5.1 +/- 1.5 to 44.0 +/- 6.8 s
      at flow rates of 0.5 ml/h. Increased flow rates significantly reduced loop
      induced flow variability. A close correlation was found between zero drug
      delivery time and calculated infusion line compliance at 0.5 ml/h (linear
      regression R2 = 0.79). Lowering of the syringe pump 50 cm prolonged zero drug
      delivery time from 295.8 +/- 20.7 s with the low-compliance tube to 463.3 +/-
      24.0 s with the high-compliance infusion line. CONCLUSIONS: Infusion line
      compliance contributes to irregular drug delivery associated with vertical
      displacement of syringe pumps. Siphoning of the infusion line during patient care
      should be avoided, and flow rates of 1 ml/h or higher are recommended. Low
      compliance infusion lines are indicated whenever highly short-acting vasoactive
      drugs at low delivery rates are administered.

PMID- 10945398
TI  - Roundtable conference on tissue oxygenation in acute medicine, Brussels, Belgium,
      14-16 March 1998.
AB  - * Nutritional tissue perfusion and tissue metabolic demand are heterogeneously
      distributed. * Oxygen diffusion occurs preferentially at the precapillary
      arteriolar level. * Determination of adequacy of tissue oxygenation requires
      local organ measurements. * While there remains considerable variability in
      individual RBC transfusion practices, a recent clinical trial questioned the
      efficacy of RBC transfusion to hemoglobin concentrations greater than 80 gm/l in
      patients without heart disease [63]. * RBC substitutes, including cell-free
      hemoglobin solutions and PFC solutions are efficacious, yet may exhibit a number
      of direct vascular effects.

PMID- 10945399
TI  - Late cardiac arrhythmias after blunt chest trauma.
AB  - OBJECTIVE: Case reports of two patients who developed fatal cardiac arrhythmias
      several days after blunt chest trauma. DESIGN: Case reports. SETTING: Surgical
      intensive care unit of a university hospital. PATIENTS: A 23-year-old man and a 9
      year-old girl with blunt chest trauma and multiple further injuries following car
      crashes were transferred to our institution. Although ECG on admission was
      normal, both patients developed fatal cardiac arrhythmias after 6 and 4 days,
      respectively. In both patients, post-mortem analysis confirmed myocardial
      contusion without coronary artery lesions. Histological findings included severe
      interstitial oedema, haemorrhages and infiltration of lymphocytes and
      neutrophils, fresh myocardial necrosis and fatty degeneration. CONCLUSION: Blunt
      chest trauma with myocardial contusion may lead to fatal cardiac arrhythmias even
      after several days, particularly when other severe injuries are present. Thus, a
      normal ECG on admission and absence of cardiac arrhythmias during the first 24 h
      of intensive care treatment do not necessarily exclude the occurrence of life
      threatening arrhythmias in the further course.

PMID- 10945400
TI  - Preliminary results on nursing workload in a dedicated weaning center.
AB  - OBJECTIVE: To evaluate the nursing time required for difficult-to-wean patients
      in a dedicated weaning center (WC) and to examine the correlation of the nursing
      time with nursing workload (NW) scores and with clinical severity and dependency.
      SETTING: Four-bed WC of a pulmonary rehabilitation department. INTERVENTION:
      None. DESIGN AND MEASUREMENT: Prospective, observational study of 46 consecutive
      patients admitted to a long-term WC. Time required by items of the Time Oriented
      Score System (TOSS) and other tasks specific to respiratory intermediate
      intensive care units were evaluated for all the activities performed on each
      patient in the first 2 days after admission. Patient dependency and level of
      nursing care at admission were measured using the Dependence Nursing Scale (DNS)
      and the Intermediate Therapeutic Intervention Score System (TISS-int). The Acute
      Physiology and Chronic Health Evaluation (APACHE) II score was also recorded at
      admission. RESULTS: On the first day each patient needed 45 +/- 15% (63 +/- 23%,
      45 +/- 22%, and 29 +/- 14% for the three nursing shifts) of allocated single
      nursing time. On the TOSS on the first day patients required a daily mean 28 +/-
      10% of total available nursing time; on the second day the results did not
      change. Time of care in the first 24 h was only weakly related to DNS, APACHE II
      score, and TISS-int; only DNS was able (although weakly; r = 0.45) to predict
      minutes of nursing care. CONCLUSIONS: In difficult-to-wean patients from
      mechanical ventilation the nursing time in the first 2 days after admission is
      high. The use of TOSS may underestimate NW by about 38%. Although only DNS showed
      the ability to predict minutes of care, the weak relationship limits its value in
      clinical practice.

PMID- 10945402
TI  - Plasma thrombopoietin level after liver transplantation: relationship to cold
      ischemia time and coagulation parameters.
AB  - OBJECTIVE: To determine the relation between thrombopoietin (Tpo) levels
      following orthotopic liver transplantation (OLT), cold ischemia time and
      postoperative peripheral blood platelet count and prothrombin activity. DESIGN:
      Prospective clinical study. SETTING: Intensive care unit. PATIENTS: Fourteen
      patients with uncomplicated postoperative course after OLT. MEASUREMENTS AND
      RESULTS: Plasma Tpo, as quantified by enzyme immunoassay, rose significantly from
      194.9 +/- 45.7 pg/ml on day 1 after OLT to a peak value of 500.7 +/- 94.1 pg/ml
      on day 5 while platelet count was below normal values. Then the platelet count
      increased and reached normal values while Tpo decreased to normal. The rise of
      Tpo levels was associated with normalization of prothrombin time but peak Tpo
      concentrations were in inverse correlation with cold ischemia times. CONCLUSION:
      The extent of production of Tpo in the liver graft following OLT is affected by
      cold ischemia time. This observation may be applicable in the prevention of
      bleeding complications associated with postoperative thrombocytopenia.

PMID- 10945401
TI  - Time course of oxidative stress after major burns.
AB  - OBJECTIVE: To evaluate oxidative stress resulting from major burns in humans.
      DESIGN: Prospective clinical study with control group. SETTING: Mechanically
      ventilated adult patients admitted with more than 30% total burn surface area.
      PATIENTS AND PARTICIPANTS: 20 patients with a mean body surface burned area of
      54%. MEASUREMENTS AND RESULTS: The oxidative stress evaluation was based on
      measurements of trace elements, vitamins, antioxidant enzymatic activity and end
      products of lipid peroxidation. During the first 5 days after injury burn
      patients exhibit a decrease in selenium and antioxidant vitamins (C, beta
      carotene, lycopene) and an increase in lipid peroxidation products (TBARS).
      CONCLUSION: Our results suggest that major burn is associated with oxidative
      stress during the 5 days after the initial injury, as demonstrated by a
      simultaneous decrease in antioxidant vitamins and a large increase in TBARS.

PMID- 10945403
TI  - Massive rhabdomyolysis and multiple organ dysfunction syndrome caused by
      leptospirosis.
AB  - We report a case of leptospiral infection in a 63-year-old man who acquired the
      infection while swimming in canals and streams in Hawaii. The patient's course
      was atypical in that he was anicteric and had no evidence of meningitis when he
      presented with fever, rapidly progressive and severe rhabdomyolysis,
      thrombocytopenia, acute renal failure, and respiratory distress syndrome.
      Although he recovered after a protracted illness, he required major life support,
      including mechanical ventilation and hemodialysis. Initial antimicrobial therapy
      was designed to cover major bacterial and atypical pathogens, including
      leptospires. An in-depth work-up for causes of this catastrophic illness
      confirmed acute leptospirosis. Although rare, leptospirosis is a potentially
      lethal infection classically associated with hepatitis, azotemia, and meningitis.
      Most patients experience self-limited illness, with fever, myalgias, and malaise
      followed by an immune-mediated aseptic meningitis. A small proportion develop
      shock and multiple organ dysfunction. Whereas myalgias are ubiquitous in
      leptospiral infection, and most patients show mildly elevated muscle enzymes,
      life-threatening rhabdomyolysis is rare. This atypical case is reported to urge
      clinicians to consider leptospirosis in the evaluation of a patient with
      cryptogenic sepsis who develops multiple organ dysfunction associated with
      rhabdomyolysis. Appropriate antimicrobial therapy, with penicillin or
      doxycycline, can be life-saving.

PMID- 10945404
TI  - Gut perfusion in the critically ill.

PMID- 10945405
TI  - Incidence of ARDS.

PMID- 10945406
TI  - Respiratory distress caused by migration of ventriculoperitoneal shunt catheter
      into the chest cavity.

PMID- 10945407
TI  - An unusual case of the fat embolism syndrome.

PMID- 10945408
TI  - Translaryngeal tracheostomy through the intubating laryngeal mask airway in a
      patient with difficult tracheal intubation.

PMID- 10945409
TI  - Esophageal endosonography of retrotracheal structures following dilatational
      tracheostomy complication.

PMID- 10945410
TI  - Improvised system for measuring respiratory status in severe myasthenia gravis.

PMID- 10945411
TI  - Treatment of severe systemic lupus erythematosus with immunoadsorption and
      intravenous immunoglobulins.

PMID- 10945412
TI  - Saccharomyces fungemia complicating Saccharomyces boulardii treatment in a non
      immunocompromised host.

PMID- 10945413
TI  - Paraplegia due to acute spinal epidural hematoma after routine cardiac surgery.

PMID- 10945414
TI  - Delayed toxicity in acute ethanol-methanol copoisoning in a chronic alcohol
      abuser: usefulness of continuous 4-methylpyrazole (fomepizole) infusion.

PMID- 10945415
TI  - Fatal non-occlusive mesenteric infarction following digoxin intoxication.

PMID- 10945416
TI  - Cefpirome and continuous venovenous hemofiltration.

PMID- 10945417
TI  - Cefpirome and continuous venovenous hemofiltration.

PMID- 10945418
TI  - Thrombolysis after cardiopulmonary resuscitation.

PMID- 10945419
TI  - The effects of knee-ankle-foot orthoses in the treatment of Duchenne muscular
      dystrophy: review of the literature.
AB  - OBJECTIVE: A systematic review of the available literature on the effectiveness
      of knee-ankle-foot orthoses in the treatment of Duchenne muscular dystrophy.
      DESIGN: A computer search was carried out (MEDLINE 1966-97, CINAHL 1982-97) using
      the key words muscular dystrophy, rehabilitation, locomotion, braces or orthotic
      devices. References in relevant publications and nonindexed journals were also
      examined. Criteria to include and exclude articles were formulated. We used a
      systematic review procedure to evaluate the literature. Seven methodological
      criteria were formulated. RESULTS: Thirty articles describing 35 studies met the
      inclusion criteria for our review, nine studies were selected based on
      completeness of information on study population, treatment and quantitative
      presentation of the effect outcome. Operations on the lower limbs were performed
      on most patients. A concomitant programme of rehabilitation was not described
      thoroughly. A percentage success of treatment was calculated for eight studies.
      Median percentage after one year was 75.1, after two years 47.9 and after three
      years 24.3. The median for the means of independent walking was 24 months, the
      median for the means of assisted walking was 36.2 months and the median for the
      means of standing ability was 50.5 months duration. CONCLUSION: The scientific
      strength of the studies reviewed is poor. It seems that the use of knee-ankle
      foot orthoses can prolong assisted walking and standing, but it is uncertain
      whether it can prolong functional walking. The boys that benefit most have a
      relatively low rate of deterioration, are capable of enduring an operation and
      are well motivated.

PMID- 10945420
TI  - Bobath or motor relearning programme? A comparison of two different approaches of
      physiotherapy in stroke rehabilitation: a randomized controlled study.
AB  - OBJECTIVE: To examine whether two different physiotherapy regimes caused any
      differences in outcome in rehabilitation after acute stroke. DESIGN: A double
      blind study of patients with acute first-ever stroke. Sixty-one patients were
      consecutively included, block randomized into two groups, and stratified
      according to gender and hemiplegic site. Group 1 (33 patients) and group 2 (28
      patients) had physiotherapy according to Motor Relearning Programme (MRP) and
      Bobath, respectively. The supplemental treatment did not differ in the two
      groups. MAIN OUTCOME MEASURES: The Motor Assessment Scale (MAS), the Sodring
      Motor Evaluation Scale (SMES), the Barthel ADL Index and the Nottingham Health
      Profile (NHP) were used. The following parameters were also registered: length of
      stay in the hospital, use of assistive devices for mobility, and the patient's
      accommodation after discharge from the hospital. RESULTS: Patients treated
      according to MRP stayed fewer days in hospital than those treated according to
      Bobath (mean 21 days versus 34 days, p = 0.008). Both groups improved in MAS and
      SMES, but the improvement in motor function was significantly better in the MRP
      group. The two groups improved in Barthel ADL Index without significant
      differences between the groups. However, women treated by MRP improved more in
      ADL than women treated by Bobath. There were no differences between the groups in
      the life quality test (NHP), use of assistive devices or accommodation after
      discharge from the hospital. CONCLUSION: The present study indicates that
      physiotherapy treatment using the MRP is preferable to that using the Bobath
      programme in the acute rehabilitation of stroke patients.

PMID- 10945421
TI  - A randomized controlled trial of strapping to prevent post-stroke shoulder pain.
AB  - OBJECTIVE: To determine whether strapping the shoulder in hemiplegic stroke
      patients: (1) prevents the development, or reduces the severity, of shoulder
      pain, (2) preserves range of movement in the shoulder, and (3) improves the
      functional outcomes for the arm and patient overall. DESIGN: A prospective,
      randomized, single-blind controlled trial of shoulder strapping versus no
      strapping. SETTING: Care of the elderly wards in a teaching hospital,
      Christchurch, New Zealand. SUBJECTS: All patients admitted with an acute
      hemiplegic stroke, who had persisting weakness of shoulder abduction.
      INTERVENTION: The treatment group had their affected shoulder strapped for six
      weeks from randomization in addition to standard physiotherapy. MAIN OUTCOME
      MEASURES: All subjects were assessed at entry (week 0), at end of the treatment
      phase (week 6) and two months later (week 14). A visual analogue scale (VAS) was
      used to assess shoulder pain severity whereas shoulder range of movement to the
      point of pain (SROMP) assessed passive range of movement and pain. Functional
      Independence Measure (FIM), Motor Assessment Scale (MAS) and Rankin Disability
      Index measured functional outcomes. RESULTS: Ninety-eight subjects participated
      (49 strapped, 49 controls). Intention to treat analysis showed no significant
      difference in pain, range of movement or functional outcomes after the
      intervention phase or at the final assessment. However there were trends for less
      pain at six weeks (VAS, p = 0.11) and better final upper limb function (MAS, p =
      0.16) in strapped patients. Skin reactions were uncommon (6.1%). The presence of
      neglect or sensory loss, but not subluxation, at baseline was independently
      associated with poor outcome. Range of movement was lost early (mean difference
      SROMP between hemiplegic and contralateral shoulders at baseline = 15.2 degrees
      (95% CI 10.9-19.5)) and continued throughout the study. Shoulder strapping did
      not alter the rate at which range of movement was lost. CONCLUSIONS: No
      significant benefit with shoulder strapping was demonstrated and reasons for this
      are discussed. Range of movement in the hemiplegic shoulder is lost very early
      and any preventive treatments need to begin within the first 1-2 days after a
      stroke.

PMID- 10945422
TI  - Discharge and follow-up for people with stroke: what happens and why.
AB  - OBJECTIVE: To assess the quality of the process of discharge from hospital and
      follow-up services for people with stroke. DESIGN: A criterion-based process
      audit and basic outcome measures, combined with surveys of patients' satisfaction
      and staff opinion of the service. SETTING: All units treating stroke patients in
      a health care district including an acute and a community NHS trust, and 23
      participating GP practices. SUBJECTS: Process audit: documented notes of 98
      stroke patients admitted and discharged over a four-month period. Patient
      satisfaction survey: 93 surviving stroke patients. Staff opinion survey: general
      practitioners, hospital doctors, therapists and nurses treating stroke patients
      throughout the district. RESULTS: A poor level of service was found. The main
      shortcomings were poor communication and liaison and a narrow focus of
      rehabilitation which concentrated on the assessment and provision of basic home
      care and activities of daily living (ADL) required to obtain discharge. There was
      a paucity of provision beyond this most basic level and little follow-up after
      discharge. Pass rates against agreed criteria were: communication between staff
      and patients/carers 47%, liaison between staff 44%, assessment of home-based
      needs 48%, assessment of domestic skills 15.5%. Fifty-one per cent of patients
      were referred for follow-up therapy and of these 72% started follow-up therapy
      within six weeks of discharge, only 27% had any follow-up assessment of activity
      levels and well-being. Patients were dissatisfied with the information, support
      services and therapy they received. The main reasons for the shortcomings were
      lack of awareness of the services provided, professionals' low expectations of
      patients' abilities, and limitations of community-based therapy services.
      CONCLUSIONS: Evidence from other publications suggests that these results do not
      indicate a service that is any worse than other districts, rather it represents
      the poor deal offered to stroke patients. By comprehensively assessing several
      aspects of the service together this methodology has been able to reveal these
      inadequacies and the reasons for them.

PMID- 10945424
TI  - What is balance?
AB  - Balance is a term frequently used by health professionals working in a wide
      variety of clinical specialities. There is no universally accepted definition of
      human balance, or related terms. This article identifies mechanical definitions
      of balance and introduces clinical definitions of balance and postural control.
      Postural control is defined as the act of maintaining, achieving or restoring a
      state of balance during any posture or activity. Postural control strategies may
      be either predictive or reactive, and may involve either a fixed-support or a
      change-in-support response. Clinical tests of balance assess different components
      of balance ability. Health professionals should select clinical assessments based
      on a sound knowledge and understanding of the classification of balance and
      postural control strategies.

PMID- 10945423
TI  - Effects of upper and lower limb static exertions on global synkineses in
      hemiparetic subjects.
AB  - OBJECTIVES: Global synkineses are nonpurposive pathological involuntary muscle
      activities or movements elicited at several or all of the joints of the affected
      limb or limbs during voluntary forceful resisted contractions. The purpose of
      this study was to assess the effect of upper and lower limb exertions on
      manifestations of upper limb global synkineses in hemiparetic subjects. DESIGN:
      Involuntary muscle activities on the affected upper limb of 11 hemiparetic
      subjects and on the left or right upper limb of 10 control subjects were recorded
      using surface electromyography during successive bilateral maximal ankle
      exertions and during contralateral grips. RESULTS: Significant differences in the
      level of involuntary electromyography (EMG) activities were observed between
      experimental conditions (ANOVAs, p < 0.05). EMG levels in hemiparetic subjects
      were significantly higher during contralateral grip tasks than during the ankle
      exertions. CONCLUSION: These results suggest that upper limb global synkinases
      are more prevalent in specific tasks and that this task specificity may reflect
      the neurophysiological mechanisms involved in the generation of global
      synkinases.

PMID- 10945425
TI  - The Wessex Head Injury Matrix (WHIM) main scale: a preliminary report on a scale
      to assess and monitor patient recovery after severe head injury.
AB  - OBJECTIVE: To develop a behavioural assessment based on observations of patients
      recovering after severe head injury whereby data could be collected by
      observation and by testing everyday tasks. DESIGN: A prospective observational
      study of a cohort of 88 consecutive hospital admissions with severe head injury.
      SETTING: Two district general hospitals in the UK. PATIENTS: Eighty-eight
      consecutive admissions with severe traumatic head injury. Ages ranged from 14 to
      67 years, mean coma duration was 14 days and mean duration of post traumatic
      amnesia (PTA) was 56 days. RESULTS: Fifty-eight items of behaviour were
      identified. Paired preference analysis was used to identify a sequence of
      recovery of these behaviours. The sequence began with arousal and led on to
      behaviours signalling recovery of social interaction and communication.
      Subsequent behaviours indicated increasing cognitive organization and return of
      orientation and memory. The behaviours on the scale are hierarchical and range
      from coma to emergence from PTA. CONCLUSIONS: A scale to assess patients and
      monitor cognitive recovery after severe head injury has been developed. While
      individual patients will show some departures from the sequence identified, the
      scale helps to make explicit the earliest stages of natural recovery patterns
      after head injury.

PMID- 10945426
TI  - Stroke patients' views on stroke outcomes: death versus disability.
AB  - AIMS: To determine how elderly stroke patients perceive different stroke
      outcomes, including death, relative to each other and how these views compare
      with those of age/sex-matched controls. PARTICIPANTS AND SETTING: Twenty-eight
      elderly patients discharged from hospital with an acute stroke causing
      hemiplegia. Twenty-eight age/sex-matched control patients from the same hospital
      who had never had a stroke or transient ischaemic attack. METHODS: Patients and
      controls were asked to rank 11 clinical scenarios of potential stroke outcomes,
      from the most to the least desirable outcome. RESULTS: There was a striking
      bimodal distribution for sudden painless death in both groups. Painless death was
      preferred to even a minor stroke disability in over one-third of elderly
      individuals, whilst 20% would prefer severe disability rather than painless
      death. Sixty-nine per cent of stroke patients and 82% of controls ranked death as
      preferable to severe disability. Stroke patients may be more tolerant of
      disability (compared to death) than their controls (39% patients and 61% controls
      preferred death to any disability, p = 0.11). CONCLUSIONS: Our results suggest
      that many elderly individuals would rather die than be alive and severely
      disabled. This may have important implications for acute stroke treatments such
      as thrombolysis.

PMID- 10945427
TI  - Reliability of tremor measurements using a multidimensional electromagnetic
      sensor system.
AB  - OBJECTIVE: To investigate the reliability of repeated measurements of normal
      physiological tremor made with a multidimensional measurement system. EQUIPMENT:
      Measurements of postural upper limb tremor at the hand were made in 10 normal
      subjects using a 3Space Fastrak (Polhemus, Inc.) which detects movement over six
      degrees-of-freedom (three of the measurement directions were examined). DATA
      COLLECTION: Reliability was assessed for two alternative upper limb postures (arm
      straight or bent) and data were collected on two days, twice at each session, to
      determine the repeatability between and within recording sessions. DATA ANALYSIS:
      The data were split into segments and subjected to autoregressive (AR) modelling.
      Three parameters (one for each of the measurement directions examined) were
      extracted from the models and used as variables for the reliability analysis.
      STATISTICAL TESTS: Variation within and between sessions was assessed by finding
      the median differences between efforts and days for each subject and then finding
      the overall median value and the corresponding 97.9% confidence intervals for
      each movement. This produced estimates of the population median value and
      indicated the precision of the estimates. RESULTS: All the confidence intervals
      encompassed the zero median difference point indicating that, in the population,
      this technique would produce repeatable results. For between-efforts comparisons
      there was some evidence that data collected for the bent arm posture were more
      repeatable than for a straight arm. CONCLUSION: Normal physiological tremor can
      be measured reliably, within and between sessions, using the 3Space Fastrak
      system.

PMID- 10945428
TI  - Inter-rater reliability of the Frenchay activities index in patients with stroke
      and their careers.
AB  - OBJECTIVE: To measure the inter-rater reliability of the interview-administered
      version of the Frenchay Activities Index (FAI). DESIGN: Comparison of FAI score
      on the same person when administered by two raters (mean time between interviews
      15.2 days). SUBJECTS: Fifty-nine Oxfordshire residents who either had had a
      stroke (n = 35) or were the main carer (n = 24). RESULTS: The 95% limits of
      agreement for the FAI totals were -9.9 to +8.4. The kappa statistic for nine of
      the 15 items showed a good level of agreement between the two research interviews
      (0.64-0.80). The other six items showed fair or moderate strength of agreement
      (0.26-0.52). Three items showed significant differences between the two raters p
      < 0.05 (Wilcoxon's sign paired rank sum test). The mean difference between the
      total scores was -0.76 (95% confidence interval from -1.98 to 0.46). Spearman's
      rho correlation coefficient for FAI totals of rater B against A was r(59) = 0.93
      (p < 0.001). CONCLUSION: The FAI is a reliable tool for measuring outcome
      following stroke. Suggestions are made to strengthen the reliability, and
      consequently the validity of the measure.

PMID- 10945429
TI  - Computer recording of standard tests of visual neglect in stroke patients.
AB  - OBJECTIVE: To determine whether a computer-based method for recording
      standardized assessment of neglect identifies abnormalities in the 'process' as
      well as in the 'outcome' of such tasks. DESIGN: Prospective sequential assessment
      of patients admitted to a stroke rehabilitation unit. SUBJECTS: All consecutive
      patients with right-sided cerebrovascular accident confirmed on computerized
      tomography (CT) scan including 30 patients with neglect, 57 patients without
      neglect. An age-matched control group of 13 subjects. INTERVENTION: All patients
      were tested using the standard Rivermead Behavioural Inattention Test (BIT) and
      by computer recording of two standard tests for assessing neglect (line bisection
      and Albert's test). Age-matched controls were tested using computer recording of
      the two standard tests. MAIN OUTCOME MEASURES: Neglect was defined using the BIT
      with a cut-off score of 129. Computer recording measured the 'outcome' of tasks,
      i.e. the deviation from midline and omissions in cancellation, as well as the
      'process' of tasks, i.e. time between cancellations, components of cancellation
      time including premovement, movement and drawing time, and the starting point for
      cancellation. RESULTS: The computer recording identified significant differences
      in 'outcome' and 'process' which distinguished neglect from non-neglect patients.
      There were significant differences between non-neglect patients and age-matched
      controls with regard to 'process' measures but not with regard to 'outcome'
      measures. CONCLUSIONS: Computer recording of standard tests for assessing neglect
      identifies novel impairments with regard to the process of carrying out tasks.
      These impairments may be used to investigate changes in neglect with time, the
      response of neglect to treatment and to explore further the neuropsychological
      changes associated with neglect in stroke patients.

PMID- 10945430
TI  - The Huntingdon Day Hospital Trial: secondary outcome measures.
AB  - OBJECTIVE: To compare day hospital to day centre rehabilitation using scales to
      measure mobility, activities of daily living and quality of life. DESIGN: Single
      blind randomized controlled trial with home assessments at baseline (twice), six
      weeks and three months. SETTING: Mainly rural health district. Day hospital and
      social services day centres in market towns. INTERVENTIONS: Day hospital
      treatment or day centre rehabilitation by a physiotherapist and two health
      support workers. MAIN OUTCOME MEASURES: World Health Organization mobility scale
      scored with and without aid, Nottingham Extended Activities of Daily Living Scale
      and Nottingham Health Profile. SUBJECTS: One hundred and five physically disabled
      older patients living at home referred for day hospital rehabilitation or
      maintenance before discharge from hospital (66) or referred as outpatients (39).
      RESULTS: At three months there were no statistically significant differences
      between rehabilitation at day hospital and day centre for any of the outcome
      measurements. However, there were significant improvements between baseline and
      three months for the following subscales [mean change per six-week period (95%
      confidence interval) ]: WHO mobility subscale (with aid) -0.67 (-0.99,-0.35);
      Nottingham Health Profile mobility subscale -10 (-15.5,-4.5) Nottingham extended
      ADL mobility subscale +3.08 (1.78,4.37); Nottingham extended ADL leisure subscale
      +1.66 (0.96,2.36). CONCLUSION: There were no differences between day hospital and
      day centre in the outcomes measured. Day rehabilitation appeared to improve
      functional ability and mobility and scales reflecting these domains deserve
      further evaluation as outcome measures in this patient group. However, no
      improvement in quality of life was observed.

PMID- 10945431
TI  - Some molecular and enzymatic properties of a homogeneous preparation of
      thiaminase I purified from carp liver.
AB  - A homogeneous preparation of thiaminase I (thiamine:base 2-methyl-4
      aminopyrimidine-5-methenyl transferase, EC 2.5.1.2) was obtained from carp liver,
      for the first time from a nonbacterial source. Its molecular mass was 55 kDa by
      gel filtration and by SDS-PAGE regardless the presence of the reducing agent,
      indicating that the native enzyme consists of a single polypeptide chain. The
      determined sequence of 20 residues at the N-terminal of carp thiaminase I seemed
      to be unique. The enzyme was tested for ability to decompose a number of thiamine
      analogues. Even very extensive modifications of the thiazolium fragment were well
      tolerated, but around the pyrimidine fragment the active center seemed to exert
      steric restrictions against 1' (N)- and 2' (C)- atoms, while the 4'-amino group
      and untouched 6'-carbon atom were absolutely essential for the enzyme action.
      Numerous nucleophiles could be used by the enzyme as cosubstrates, aniline,
      pyridine, and 2-mercaptoethanol being the best among compounds tested. Protein
      chemical modification experiments indicated that histidine residues, carboxyl
      groups, and sulfhydryl groups may play specific roles in the thiaminase I
      catalyzed reaction. Like in the bacterial enzyme, a sulfhydryl group may be a
      catalytically critical active-site nucleophile. The histidine residues and
      carboxyl groups may be essential for thiamine binding to the active site.

PMID- 10945433
TI  - Hydrophilic framework in proteins?
AB  - The spatial neighborhood composition of residues was determined in a 511
      structure set by taking only side-chain atoms into account to generate a
      hydrophobicity scale. This scale is symmetrical and has been divided into seven
      functional groups. Hydrophobic (LIVFMCAWYG) and hydrophilic (PTHSQRNKED) residues
      obey an equipartition rule: not only are they found in equal proportions, but
      they play equivalent roles in many of their properties. The nearest neighbors of
      all residues are always hydrophilic. However, hydrophobic residues are mostly
      surrounded by other hydrophobic residues located at a peak at 3.9 A, while
      hydrophilic residues show three peaks at 5.0, 6.5, and 8.0 A, suggesting a
      hydrophilic structural framework. This leads us to question the importance of
      hydrophobic cores believed to be at the origin of protein folding.

PMID- 10945432
TI  - Influence of neutral salts on the hydrothermal stability of acid-soluble
      collagen.
AB  - The thermal stability of acid-soluble collagens was studied by circular dichroism
      (CD) spectroscopy. Adult bovine dermal collagen (BDC), rat-tail tendon collagen
      (RTC), and calf skin collagen (CSC) were compared. Despite some variability in
      amino acid composition and apparent molecular weight, the CD spectra for helical
      and unordered collagen structures were essentially the same for all the sources.
      The melting of these collagens occurs as a two-stage process characterized by a
      pretransition (Tp) followed by complete denaturation (Td). The characteristic
      temperatures vary with the source of the collagen; for mature collagens (BDC,
      RTC) Tp = 30 degrees C and Td = 36 degrees C, and for CSC Tp = 34 degrees C and
      Td = 40 degrees C. Neutral salts, NaCl or KCl, at low concentrations (0.02-0.2 M)
      appear to bind to the collagens and shift the thermal transitions of these
      collagens to lower temperatures.

PMID- 10945434
TI  - New genetic variants identified in donkey's milk whey proteins.
AB  - Novel genetic variants for donkey milk lysozyme and beta-lactoglobulins I and II
      have been identified by the combined use of peptide mass mapping and sequencing
      by tandem mass spectrometry in association with database searching. The novel
      donkey lysozyme variant designated as lysozyme B (Mr 14,631 Da) differed in three
      amino acid exchanges, N49 --> D, Y52 --> S, and S61 --> N, from the previously
      published sequence. Three novel genetic variants for donkey beta-lactoglobulins
      were identified. One of them is a type beta-lactoglobulin I with three amino acid
      exchanges at E36 --> S, S97 --> T, and V150 --> I (beta-lactoglobulin I B, Mr
      18,510 Da). The two others are type beta-lactoglobulins II with two amino acid
      exchanges at C110 --> P and M118--> T (beta-lactoglobulin II B, Mr 18,227 Da) and
      with three amino acid exchanges at D96 --> E, C110 --> P, and M118 -->T (beta
      lactoglobulin II C, Mr 18,241 Da). All these primary structures are closely
      related to those of homologous proteins in horse milk (percent identity >96%).

PMID- 10945435
TI  - Inhibition of Papaya latex papain by photosensitive inhibitors. 1-(4,5-dimethoxy
      2-nitrophenyl)-2-nitroethene and 1,1-dicyano-2-(4,5-dimethoxy-2-nitrophenyl)
      ethene.
AB  - 1-(4,5-Dimethoxy-2-nitrophenyl)-2-nitroethene (1) was shown to be an irreversible
      inhibitor of papain (EC 3.4.22.2), causing a complete inhibition (120 min
      preincubation, pH 8.0), assuming that it attached to Cys-25 at the active site of
      the enzyme (while a short preincubation time caused activation). Only partial
      inhibition of papain was achieved, however, with 1,1-dicyano-2-(4,5-dimethoxy-2
      nitrophenyl)-ethene (2), a compound synthesized in this work, which is also an
      irreversible inhibitor of papain. Since both compounds 1 and 2, and in each case
      of the inhibited enzyme, were 2-nitrobenzyl derivatives, they and the modified
      enzyme were expected to be photosensitive. Indeed, irradiation of the inhibited
      enzyme in the presence of mercaptoethanol resulted in a full recovery of the
      enzyme activity following inactivation with compound 1 (similar to our previous
      finding with beta-galactosidase) and up to 67% recovery following inhibition with
      compound 2.

PMID- 10945436
TI  - Photoreversible modulators of Escherichia coli beta-galactosidase. 1-Benzoyl-1
      cyano-2-(4,5-dimethoxy-2-nitrophenyl)-ethene and 1,1-dicyano-2-(4,5-dimethoxy-2
      nitrophenyl)-ethene.
AB  - Beta-galactosidase (EC 3.2.1.23) is known to be inhibited by some thiol reagents.
      1-Benzoyl-1-cyano-2-(4,5-dimethoxy-2-nitrophenyl)-ethene (1) was shown to be an
      irreversible inhibitor, while 1, 1-dicyano-2-(4,5-dimethoxy-2-nitrophenyl)-ethene
      (2) was demonstrated as a positive irreversible modulator causing a rise of up to
      186% in beta-galactosidase activity. Compound 2 is, however, an irreversible
      inhibitor of the cysteine proteinase papain (preceding paper). Kinetic values of
      beta-galactosidase at pH 8.3 with o-nitrophenyl beta-D-galactopyranoside (ONPG)
      as the substrate and for compounds 1 and 2 were determined and in view of model
      experiments, it was assumed that both compounds possibly reacted with the thiol
      side chain of Cys in the active site inducing allosteric changes in the enzyme.
      Since the enzyme, modified by compound 1 or 2, was a 2-nitrobenzyl derivative,
      near-UV irradiation resulted in a recovery of up to 91% and a reduction of the
      enzyme's activity to 90%, respectively.

PMID- 10945437
TI  - Atomic structures of two nitroxide spin labels complexed with human thrombin:
      comparison with solution studies.
AB  - Crystal structures of thrombin complexed with two spin labels called para-V, 4
      (2,2,5,5-tetramethylpyrrolidine-1-oxyl)-p-(fluorosulfonyl) benzamidine, and meta
      V, 3-(2,2,5,5-tetramethyl-pyrrolidine1-oxyl)-m-(fluorosulfonyl) benzamidine, have
      been completed at 2.0 and 3.0 A resolution, respectively. Previous electron spin
      resonance studies with these labels gave rise to a low-resolution "topography
      map" of thrombin's extended active site. These labels monitor two distinct areas
      of the thrombin active site: (1) an apolar binding site which manifests itself in
      an biphasic activation/inhibition effect on thrombin activity and (2) a region
      sensitive to alpha-thrombin autoproteolytic cleavage(s) to gamma-thrombin (Arg75
      Tyr76 and/or Arg77A-Asn78, and Lys149E-Gly150, chymotrypsin numbering). Para-V
      was found to bind along the substrate binding cleft, while meta-V was found to
      bind both at the substrate primary specificity pocket and at a site which
      interacts with the gamma-cleavage loop. These studies reaffirm that accurate
      information may be gained from solution studies and indicates the complementarity
      of solid-state studies.

PMID- 10945438
TI  - Subunit distribution of calcium-binding sites in Lumbricus terrestris hemoglobin.
AB  - The giant, approximately 3.6-MDa hexagonal bilayer hemoglobin (Hb) of Lumbricus
      terrestris consist of twelve 213-kDa globin subassemblies, each comprised of
      three disulfide-bonded trimers and three monomer globin chains, tethered to a
      central scaffolding of 36-42 linkers L1-L4 (24-32 kDa). It is known to contain 50
      80 Ca and 2-4 Cu and Zn; the latter are thought to be responsible for the
      superoxide dismutase activity of the Hb. Total reflection X-ray fluorescence
      spectrometry was used to determine the Ca, Cu, and Zn contents of the Hb
      dissociated at pH approximately 2.2, the globin dodecamer subassembly, and linker
      subunits L2 and L4. Although the dissociated Hb retained 20 Ca2+ and all the Cu
      and Zn, the globin subassembly had 0.4 to approximately 3 Ca2+, depending on the
      method of isolation, and only traces of Cu and Zn. The linkers L2 and L4,
      isolated by reversed-phase high-pressure liquid chromatography at pH
      approximately 2.2, had 1 Ca per mole and very little Cu and Zn. Electrospray
      ionization mass spectrometry of linker L3 at pH approximately 2.2 and at neutral
      pH demonstrated avid binding of 1 Ca2+ and additional weaker binding of 7 Ca2+ in
      the presence of added Ca2+. Based on these and previous results which document
      the heterogeneous nature of the Ca2+-binding sites in Lumbricus Hb, we propose
      three classes of Ca2+-binding sites with affinities increasing in the following
      order: (i) a large number of sites (>100) with affinities lower than EDTA
      associated with linker L3 and dodecamer subassembly, (ii) approximately 30 sites
      with affinities higher than EDTA occurring within the cysteine-rich domains of
      linker L3 and dodecamer subassembly, and (iii) approximately 25 very high
      affinity sites associated with the linker subunits L1, L2, and L4. It is likely
      that the low-affinity type (i) sites are the ones involved in the effects of 1
      100 mM Group IIA cations on Lumbricus Hb structure and function, namely increased
      stability of its quaternary structure and increased affinity and cooperativity of
      its oxygen binding.

PMID- 10945439
TI  - Kinetics of c-phycocyanin reaction with hypochlorite.
AB  - Hydrochlorous acid bleaches c-phycocyanin visible absorbance with a second-order
      rate constant (pH 7.4) of 1.3x10(3) M(-1) s(-1). In excess of protein, ca. 0.16
      bilin moieties are disrupted by each reacted HOCl molecule. This indicates that
      the main reaction takes place at the apoprotein level, with a total rate constant
      (in monomeric units concentration) of 2.5x10(4) M(-1) s(-1). This rate constant
      is too low to provide protection to other biomolecules under physiological
      conditions. The reported antiinflammatory properties of phycocyanin are not then
      related to the removal of HOCl. On the other hand, the rather slow reaction rate
      with HOCI could be beneficial to its role as antiinflammatory agent since it will
      allow the protein to maintain its integrity at the inflammation locus.

PMID- 10945440
TI  - Soret spectroscopic and molecular graphic analysis of human semi-beta-hemoglobin
      formation.
AB  - The interaction of heme-free alpha (alpha(o)) and heme-containing beta (beta(h))
      chains of human hemoglobin has been monitored in 0.1 M potassium phosphate
      buffer, pH 7 or 8, at 5 degrees C. Soret zero and first-derivative spectra were
      consistent with a uniform association reaction. Stopped-flow investigations
      demonstrated association rates on the order of 10(7) M(-1) s(-1). This was 100
      fold more rapid than the reported rate of combination of alpha(h) and beta(h)
      proteins. This encounter-like rate of semi-beta-hemoglobin (alpha(o)beta(h))
      formation was increased by raising the pH from 7 to 8. pH change is known to
      affect the spatial arrangement of AB-GH helical entities. Molecular graphic
      analysis of modeled alpha(o) protein superimposed over native alpha(h) protein
      revealed an apo Mb-like structure with well-defined AB-GH segments. Repositioning
      of these core helical segments, resulting in increased conformational freedom of
      the alpha1beta1 interface, was apparently responsible for the enhanced
      association properties of the alpha(o) protein.

PMID- 10945441
TI  - Mannose-specific isolectins with different hemagglutinating potencies isolated
      from Chinese daffodil (Narcissus tazetta var. chinensis) leaves.
AB  - Three mannose-specific lectins exhibiting considerable similarities in NH2
      terminal amino acid sequence were isolated from leaves of the Chinese daffodil
      Narcissus tazetta (Family Amaryllidaceae). The purification protocol involved
      extraction with an aqueous buffer, anion exchange chromatography on DEAE
      cellulose using stepwise elution with increasing salt concentrations, affinity
      chromatography on mannose-agarose, and FPLC-gel filtration on Superose 12. From
      the peak unadsorbed on DEAE-cellulose, and two peaks adsorbed on the ion
      exchanger and eluted respectively with 0.2 M Tris-HCl buffer and 0.5 M NaCl, were
      prepared fractions which yielded isolectins 1, 2, and 3 after adsorption on
      mannose-agarose and FPLC-gel filtration. All three isolectins were homodimers
      with a molecular weight of 26 kDa. The lectin unadsorbed on DEAE-cellulose had
      the lowest, while the most strongly adsorbed lectin had the highest
      hemagglutinating activity.

PMID- 10945442
TI  - On the statistical significance of electrophysiological steady-state responses.
AB  - Steady-state stimulation is a useful paradigm in many physiologic and clinical
      situations, for ERG, Pattern-ERG and VEP. One of the advantages is the easy
      evaluation of the response via Fourier analysis. However, the question whether a
      given response is statistically significant or not has received little attention
      so far, although it is especially relevant in high noise, low amplitude
      recordings, as often occur in pathologic conditions. A given response is
      statistically significant if it is unlikely that its value is due to noise
      fluctuations. Thus appropriate estimates of noise and response are required. We
      have analytically derived formulas for the statistical significance of a given
      signal-to-noise-ratio s, based on two different estimates of noise: (1) Noise
      estimate by a 'no stimulus' recording, or by a '+/-average'. The former needs an
      additional recording, the latter can simultaneously be calculated as the standard
      average. (2) Noise is estimated as the average of the two neighboring spectral
      lines (one below, and one above the response frequency). Analytical solutions
      were obtained for both noise estimates that can easily be evaluated in all
      appropriate recordings. Noise estimate (1) performs much poorer than noise
      estimate (2), as can be seen from the following landmark values: Typical
      significance levels of 5%, 1%, and 0.1% require s values of 4.36, 9.95, and 31.6
      (1), and 2.82, 4.55, and 8.40 (2). The noise estimate based on the neighboring
      frequencies can be easily applied after recording, provided that the noise
      spectrum is reasonably smooth around the response and frequency-overspill was
      avoided. It allows a quantitative assessment of low responses in physiological
      threshold analyses and pathological conditions, e.g., 'submicrovolt flicker-ERG'.

PMID- 10945443
TI  - Comparisons of the amplitude size and the reproducibility of three different
      electrodes to record the corneal flash electroretinogram in rodents.
AB  - To compare corneal electrodes commonly used in rodent eyes for repeat and left
      versus right eye accuracy and variability to record the flash electroretinogram
      (ERG). Animals studied were eight C57BL/6 mice and eight rats of the Wistar
      strain. Scotopic ERGs were recorded from eyes of dark-adapted anesthetized
      rodents to compare a custom-made gold-wire contact lens electrode (CLE), a cotton
      wick silver-silver chloride electrode (SCLE), and a coiled stainless steel wire
      electrode (SSE). Compared to SCLE and SSE. the potentials recorded by CLE are
      characterized by significantly larger ERG amplitudes and oscillatory potentials
      in both rats and mice (p <0.0001). In analyzing test-retest data comparing the
      three different electrodes the coefficient of variation was smaller (range, 10.3
      15.5%) and the interclass correlation coefficient (0.77-0.93) showed a better
      agreement for the CLE. Recording scotopic ERGs with custom-made gold-wire contact
      lens electrodes records large amplitudes and shows a good reproducibility and
      reliability to monitor retinal function in rodent eyes.

PMID- 10945444
TI  - Effect of sleep state on the flash visual evoked potential. A case study.
AB  - Controversy exists regarding the influence of sleep state on the flash visual
      evoked potential. This study recorded the visual evoked potential in a new-born
      infant in four different sleep states; wakefulness. drowsiness, active sleep and
      quiet sleep over a five hour period. The infant's heart rate, breathing rate and
      breathing regularity were also recorded. It was clear that when this subject was
      awake the VEPs recorded differed substantially from those recorded when sleeping.
      Two of the four main components had shorter peak latencies, one component was
      prolonged and one of the peak to trough amplitudes was consistently smaller when
      alert. This study highlights an important and often overlooked aspect of
      developmental research that the state of the infant may affect developmental
      measures.

PMID- 10945445
TI  - Autologous limbal transplantation in unilateral chemical burns.
AB  - PURPOSE: To describe the results of autologous limbal transplantation in the
      treatment of unilateral chemical burns. PATIENTS AND METHODS: Two patients, a 40
      year-old male (case 1) and a 35-year-old male (case 2), experienced grade III
      chemical trauma and were treated with autologous limbal grafting (case 1) after a
      postaccident period of 3 and 9 months, respectively. Change in visual acuity,
      epithelial healing time and postsurgical topography healing patterns were
      documented. RESULTS: Snellen visual acuity improved from 0.1 to 1.0 in both
      cases. Epithelial healing time for cases 1 and 2 were 4 and 2 weeks,
      respectively. Corneal topography of case 1 showed an induced inferior steepness
      type of asymmetrical astigmatism in the graft area. Serial topography showed no
      induced astigmatism in the donor eyes. CONCLUSION: Autologous limbal grafting is
      an adequate treatment for selected cases of unilateral chemical burns and
      facilitates rapid improvement in visual function. Early limbal grafting in case 1
      resulted in rapid re-epithelialization and prevention of complications.

PMID- 10945446
TI  - The long term effects of unilateral corneal scars.
AB  - The main purpose of this study was to evaluate the long term effects of
      unilateral dense central corneal scars on the axial length and development of
      lens opacities. We included 12 patients with unilateral dense central corneal
      scars of early onset before the age of seven years. This study served as
      naturally-controlled experiment and demonstrated a statistically significant
      increase in ocular axial length and decrease in the incidence of cataract in the
      eye with central corneal scar. Visual deprivation induced by unilateral central
      corneal scars occurring in early childhood leads to increase in the ocular axial
      length, and decrease in the incidence of cataract.

PMID- 10945447
TI  - Human amniotic membrane in the reconstruction of the ocular surface.
AB  - We sought to determine the efficacy of amniotic membrane transplantation (AMT) in
      the reconstruction of ocular surface. AMT was performed on 40 eyes with following
      indications: I, persistent corneal ulceration (n = 12); II, impending perforation
      (n = 6); III, persistent epithelial defect on the corneal graft (n = 6); IV,
      recurrent pterygia (n = 10), and V, risk of conjunctival scarring (n = 6).
      Amniotic membrane was prepared from a fresh placenta under sterile conditions,
      washed with BSS containing penicillin, streptomycin, neomycin and amphotericin B
      and stored at -80 degrees C in 1:1 InoSol:Glycerol solution. Donor serological
      test for HIV, HBV and HCV were all negative. Associated surgical procedures
      according to indication were performed. Healing of the corneal ulcer in Group I
      was obtained in 67% of eyes at 1-3 weeks after surgery, Group II: AMT was
      followed by 'a chaud' keratoplasty in 33% and by planned keratoplasty in 67%
      patients, Group III: healing of the defect in 33% of eyes in 2-5 postoperative
      weeks, Group IV: no recurrence of pterygium ingrowth in 70% in the follow up
      period of 6-14 months, and V: 84% of patients had good eye motility without any
      synechia formation. We concluded that AMT have shown to be effective in enhancing
      healing of the corneal defects, in prevention of symblepharon formation and
      recurrent pterygium ingrowth. In case of impending perforation, AMT alone was not
      a method of treatment but is useful as a first step procedure in preparing the
      eye for the corneal transplantation.

PMID- 10945448
TI  - The treatment of newly diagnosed patients with glaucoma or with ocular
      hypertension in The Netherlands: an observational study of costs and initial
      treatment success based on retrospective chart review.
AB  - To determine the health care resource use and costs of patients with glaucoma or
      ocular hypertension in the Netherlands during the first 2 years after primary
      diagnosis, we performed a study based on retrospective chart review. Data of 200
      patients and their health care resource use were collected in five hospitals.
      Unit-prices were calculated using micro costing in two hospitals. The mean 2-year
      costs per patient were estimated to be US$ 877. Outpatient visits to the
      ophthalmologist and medications were the cost-driving factors, and were
      responsible for 40 and 30% of total costs, respectively. Total costs were
      considered to be low, when compared to the estimated costs per patient in Sweden
      and the USA. In multiple least-squares regression only baseline IOP-value, the
      change in IOP-value between baseline and the next visit and the hospital of
      treatment were significantly related with total costs. The variation in costs
      between patients largely depended on whether or not a patient had undergone
      surgery.

PMID- 10945449
TI  - Recombinant antibodies: a new reagent for biological agent detection.
AB  - Antibodies are critical reagents used in several biodetection platforms for the
      identification of biological agents. Recent advances in phage display technology
      allow isolation of high affinity recombinant antibody fragments (Fabs) that may
      bind unique epitopes of biological threat agents. The versatility of the
      selection process lends itself to efficient screening methodologies and can
      increase the number of antigen binding clones that can be isolated. Pilot scale
      biomanufacturing can then be used for the economical production of these
      immunoglobulin reagents in bacterial fermentation systems, and expression vectors
      with hexahistidine tags can be used to simplify downstream purification. One such
      Fab reagent directed against botulinum neurotoxin A/B has been shown to be
      sensitive in a variety of assay formats including surface plasmon resonance
      (SPR), flow cytometry, enzyme linked immunosorbent assay (ELISA), and hand-held
      immunochromatographic assay. Recombinant antibodies can provide another source of
      high quality detection reagents in our arsenal to identify or detect pathogens in
      environmental samples.

PMID- 10945450
TI  - Rapid identification of biological warfare agents using an instrument employing a
      light addressable potentiometric sensor and a flow-through immunofiltration
      enzyme assay system.
AB  - An instrument employing a light addressable potentiometric sensor and a flow
      through immunofiltration-enzyme assay system has been developed for the rapid and
      specific identification of biological warfare (BW) agents. The system has been
      designed to assay for up to eight agents simultaneously and provides an
      indication of the absence or presence of a threat within 15 min. Parameters
      affecting the mixing of the reagents within the instrument's fluidic lines were
      investigated and optimized. Measurements of blank samples and samples containing
      Bacillus subtilis spores in the concentration range of 10(4) to 10(6) cfu/ml
      indicate the limit of detection (LOD) is 3 x 10(3) cfu/ml for B. subtilus.
      Although the LOD is higher than that of several technologies currently under
      development, this instrument offers an immediate interim approach for addressing
      the need to rapidly detect biological warfare agents in the field.

PMID- 10945451
TI  - Multi-analyte interrogation using the fiber optic biosensor.
AB  - The capabilities of the portable, automated fiber optic biosensor, RAPTOR, have
      recently been evaluated. Developed to perform rapid fluoroimmunoassays in the
      field, the RAPTOR was designed to test samples for up to four different target
      analytes simultaneously. Assay time could be varied from a 3-min rapid screen to
      a standard 10-min test. A trial of 203 blind samples tested for Staphylococcal
      enterotoxin B, ricin, Francisella tularensis, and Bacillus globigii has been
      conducted. Sensitivities obtained were 10, 50 ng/ml, 5 x 10(5), and 5 x 10(4)
      cfu/ml, respectively.

PMID- 10945452
TI  - Optical flow-cell multichannel immunosensor for the detection of biological
      warfare agents.
AB  - An automated optical flow cell multichannel immunosensor for the detection and
      identification of toxins, viruses and bacterial particles is presented. A solid
      phase ELISA, based on a peroxidase label for signal generation and on fused
      silica capillaries as a support for immobilized antibodies, has been employed for
      analyte detection and identification. The sensing and signal transducing
      component of the sensor consists of a light-emitting diode and a photodetector.
      The device is fitted with three channels allowing the simultaneous detection of
      three agents. An integrated flow injection analysis system ensures automation of
      the assay cycles. Data on the detection of the bacterial toxin staphylococcal
      enterotoxin B (SEB), the bacteriophage M13 as a viral agent, and Escherichia coli
      as a bacterial agent are presented.

PMID- 10945453
TI  - Array biosensor for detection of biohazards.
AB  - A fluorescence-based biosensor has been developed for simultaneous analysis of
      multiple samples for multiple biohazardous agents. A patterned array of
      antibodies immobilized on the surface of a planar waveguide is used to capture
      antigen present in samples; bound analyte is then quantified by means of
      fluorescent tracer antibodies. Upon excitation of the fluorophore by a small
      diode laser, a CCD camera detects the pattern of fluorescent antibody:antigen
      complexes on the waveguide surface. Image analysis software correlates the
      position of fluorescent signals with the identity of the analyte. This array
      biosensor has been used to detect toxins, toxoids, and killed or non-pathogenic
      (vaccine) strains of pathogenic bacteria. Limits of detection in the mid-ng/ml
      range (toxins and toxoids) and in the 10(3)-10(6) cfu/ml range (bacterial
      analytes) were achieved with a facile 14-min off-line assay. In addition, a
      fluidics and imaging system has been developed which allows automated detection
      of staphylococcal enterotoxin B (SEB) in the low ng/ml range.

PMID- 10945454
TI  - Rapid detection and identification of biological and chemical agents by
      immunoassay, gene probe assay and enzyme inhibition using a silicon-based
      biosensor.
AB  - A rapid biosensor assay procedure that utilizes biotin streptavidin mediated
      filtration capture onto nitrocellulose membrane, in conjunction with a silicon
      based light-addressable potentiometric sensor (LAPS) was developed for detection
      and identification of biological and chemical threat agents. Sandwich
      immunoassays, nucleic acid hybridization assays and enzyme inhibition assays are
      described. For immunoassays, the lower limits of detection (LOD) per 100-microl
      sample were approximately 5 pg/ml for protein (Staphylococcal enterotoxin B), 2
      ng/ml for virus (Newcastle disease virus), and 20 ng/ml for vegetative bacteria
      (Brucella melitensis). In a dual gene probe assay format, the LOD was 0.30 fmol
      (1.8 x 10(8) copies per 60-microl) of single stranded target DNA. Enzyme
      inhibition assays on the LAPS using acetylcholinesterase were able to detect
      soman and sarin in aqueous samples at 2 and 8 pg (100 and 600 pM), respectively.
      The assays were easy to perform and required a total time equal to the reaction
      period plus about 15 min for filtering, washing and sensing. The assay format is
      suitable for detection of a wide range of infectious and toxic substances. New
      assays can be developed and optimized readily, often within 1 or 2 days.

PMID- 10945455
TI  - The BARC biosensor applied to the detection of biological warfare agents.
AB  - The Bead ARray Counter (BARC) is a multi-analyte biosensor that uses DNA
      hybridization, magnetic microbeads, and giant magnetoresistive (GMR) sensors to
      detect and identify biological warfare agents. The current prototype is a table
      top instrument consisting of a microfabricated chip (solid substrate) with an
      array of GMR sensors, a chip carrier board with electronics for lock-in
      detection, a fluidics cell and cartridge, and an electromagnet. DNA probes are
      patterned onto the solid substrate chip directly above the GMR sensors, and
      sample analyte containing complementary DNA hybridizes with the probes on the
      surface. Labeled, micron-sized magnetic beads are then injected that specifically
      bind to the sample DNA. A magnetic field is applied, removing any beads that are
      not specifically bound to the surface. The beads remaining on the surface are
      detected by the GMR sensors, and the intensity and location of the signal
      indicate the concentration and identity of pathogens present in the sample. The
      current BARC chip contains a 64-element sensor array, however, with recent
      advances in magnetoresistive technology, chips with millions of these GMR sensors
      will soon be commercially available, allowing simultaneous detection of thousands
      of analytes. Because each GMR sensor is capable of detecting a single magnetic
      bead, in theory, the BARC biosensor should be able to detect the presence of a
      single analyte molecule.

PMID- 10945456
TI  - The development of immunoassays to four biological threat agents in a
      bidiffractive grating biosensor.
AB  - A critical need exists for a field deployable biosensor to detect environmental
      infectious agents in collected air samples rapidly, with sensitivity and
      specificity approaching that of standard laboratory procedures. The ideal sensor
      would analyze unknown samples in minutes, have programmable operation for
      unattended sample analysis, and be capable of multiple agent analysis for a
      number of agents. The goal of this project was to further the development of the
      bidiffractive grating biosensor (BDG) created through collaboration between
      Battelle Memorial Institute (BMI), Hoffman LaRoche (HLR), and the Naval Medical
      Research Command (NMRC). This manuscript details the development, optimization,
      and evaluation of this device as a potential field deployable biosensor. Well
      characterized immunochemical reagents developed by the Biological Defense
      Research Department (BDRD) at NMRI were employed to develop assays in the BDG.
      These results were compared to those obtained with antigen capture enzyme linked
      immunosorbent assays (ELISAs). Four separate antigens were evaluated:
      Staphylococcus aureus enterotoxin B (SEB), ricin (RIC), Francisella tularensis
      (FT), and Clostridium botulinum toxin (BOT).

PMID- 10945457
TI  - Detection of biological threat agents by immunomagnetic microsphere-based solid
      phase fluorogenic- and electro-chemiluminescence.
AB  - This article reviews the recent development of two solid-phase chemiluminescence
      based techniques, fluorogenic-chemiluminescence (FCL) and electro
      chemiluminescence (ECL) for detection of biological threat agents. Both
      techniques entail a labeled sandwich immunoassay. The objectives of this work are
      to develop advanced techniques for sensitive and effective detection of a target
      analyte, particularly in cases where the analysis includes complex samples
      containing multiple contaminating factors. Other important considerations in
      developing such detection techniques include the ease of use, the rapid
      determination of the results, and system automation for field applications. In
      FCL, alkaline phosphatase is used as a label and this technique utilizes the dual
      features of fluorescence and visual color generated upon the presence of the
      fluorogenic compound, AttoPhos. The assay reaction is determined by measuring the
      fluorescence. In ECL, the label is a ruthenium-trisbipyridal, which is excited to
      a higher energy state by an electric current-driven redox reaction, and the
      extent of the reaction is assessed via photon emission. Both techniques depend
      upon the magnetic separation technique as a means to isolate the target
      immunological agents from the sample for analysis. This magnetic capture system
      allows for a reaction to occur on the electron effective-transfer zone in the ECL
      and also provides the reaction site for the labeled sandwich in the FCL.
      Comparative studies of these two techniques for detection of biological threat
      agents have been performed and the advantages of using magnetic microspheres
      versus conventional solid-phase matrices are discussed.

PMID- 10945458
TI  - An automated, handheld biosensor for aflatoxin.
AB  - A new immunoaffinity fluorometric biosensor has been developed for detecting and
      quantifying aflatoxins, a family of potent fungi-produced carcinogens that are
      commonly found in a variety of agriculture products. They have also been cited as
      a biological agent under weapons development. The handheld, self-contained
      biosensor is fully automatic, highly sensitive, quick, quantitative, and requires
      no special storage. Approximately 100 measurements can be made before
      refurbishment is required, and concentrations from 0.1 parts per billion (ppb) to
      50 ppb can be determined in <2 min with a 1 ml sample volume. The device operates
      on the principles of immunoaffinity for specificity and fluorescence for a
      quantitative assay. The analytic procedure is flexible so that other chemical and
      biological analytes could be detected with minor modifications to the current
      device. Advances in electro-optical components, electronics, and miniaturized
      fluidics were combined to produce this reliable, small, and versatile instrument.

PMID- 10945459
TI  - A microfluidic cartridge to prepare spores for PCR analysis.
AB  - A prototype cartridge system is described that rapidly disrupts Bacillus spores
      by sonication, adds PCR reagent to the disrupted spores, and dispenses the
      mixture into a PCR tube. The total time to automatically process the spores in
      the cartridge and then detect the spore DNA by real-time PCR was 20 min.

PMID- 10945460
TI  - Development of instrumentation to allow the detection of microorganisms using
      light scattering in combination with surface plasmon resonance.
AB  - This paper describes work carried out to develop a biosensor which allows two
      separate detection principles to operate simultaneously at the same surface. A
      prototype device was constructed that provided Kretschmann-configuration surface
      plasmon resonance (SPR) measurement of refractive index (RI) changes using an 820
      nm LED light source, whilst a 635 nm diode laser was used to produce light
      scattering signals from bacterial spores. Both effects occurred at a gold-coated
      surface. The RI changes were measured conventionally from the side of the gold
      layer nearer to the light sources. The scattered light was imaged from the
      opposite face which was in contact with the aqueous sample. Specific detection of
      bacterial spores through the light scattering mode using antibody capture was
      investigated. The flow dynamics and interactions with the surface of individual
      spores were observed. A comparison with SPR for detection using the same
      antibody/antigen pair was made. Spore suspensions that were readily detectable by
      light scattering at 10(7) ml(-1) did not provide significant responses by SPR.
      The potential for future developments is discussed.

PMID- 10945461
TI  - Red diode laser induced fluorescence detection with a confocal microscope on a
      microchip for capillary electrophoresis.
AB  - A highly sensitive laser induced fluorescence (LIF) detection system based on a
      635 nm laser diode and cyanine-5 (Cy-5) dye, is described for use with a planar,
      microfluidic, capillary electrophoresis (CE) chip. The CE-chip is able to
      determine a protein biological threat agent simulant, ovalbumin (Ov), by
      performing an immunoassay separation of Cy-5 labeled anti-ovalbumin from its
      complex with Ov, in under 30 s. A confocal, epiluminescent detection system
      utilizing a photomultiplier tube gave optimum results with a 400 microm pinhole,
      an Omega 682DF22 emission filter, a 645DRLP02 dichroic mirror, a 634.54 +/- 5 nm
      excitation filter, and a Power Technology ACMO8 635 nm laser operated at 11.2 mW.
      Using this detector, a microchip CE device with a separation efficiency of 42,000
      plates and an etch depth of 20 microm, gave a concentration detection limit of 9
      pM Cy-5. This limit corresponds to the determination of 4560 injected molecules
      and detection of 900 of these molecules, given a probe volume of 1.6 pl and a
      probing efficiency of 20%.

PMID- 10945462
TI  - Immobilization of neural cells in three-dimensional matrices for biosensor
      applications.
AB  - To overcome logistical difficulties with current designs of cell- or tissue-based
      biosensors which have individual cells or tissue slices immobilized on membranes
      or microelectrode arrays, we have proposed a system that uses three-dimensional
      cultures of neural cells immobilized in hydrogel matrices. In this design,
      immobilized cells would be maintained in a reservoir and then transferred to a
      detector platform when needed for analysis. The development of such a system
      relies upon a renewable supply of cells and the ability to culture cells for long
      periods of time in three-dimensions while maintaining their physiological
      function. To investigate the ability to culture neural cells in 3D matrices,
      embryonic rat cortical neurons and astrocytes were immobilized by matrix
      entrapment in a novel sugar poly(acrylate) hydrogel and collagen gels. The sugar
      poly(acrylate) hydrogel does not appear to support neural cell growth as a result
      of a lack of cell adherence, small pore size and, possibly, harshness of
      synthesis conditions. In contrast, collagen gels support the growth of cortical
      neurons, astrocytes, as well as neural progenitor cells. Evidence is also
      presented from immunocytochemistry and patch-clamp measurements which shows that
      neural progenitor cells proliferate in culture and can be induced to
      differentiate into neural cell types. Thus, they potentially represent a
      renewable cell source.

PMID- 10945463
TI  - Current awareness in biosensors & bioelectronics.

PMID- 10945464
TI  - Mouse proteasomal ATPases Psmc3 and Psmc4: genomic organization and gene
      targeting.
AB  - PSMC3 and PSMC4, components of the 19S complex of the 26S proteasome, show a
      significant degree of amino acid similarity, especially in the conserved ATPase
      domain (CAD). In this study, we characterized the mouse Psmc3 and Psmc4 genes.
      The genomic structures of both genes showed a significant degree of similarity.
      The Psmc3 gene was composed of 12 coding exons, whereas the Psmc4 gene had 11
      exons. Exons encoding the leucine zipper domain and CAD were identical in number
      between the Psmc3 and Psmc4 genes. The Psmc3 gene mapped to mouse chromosome 2,
      whereas Psmc4 mapped to chromosome 7. We further addressed the biological roles
      of Psmc3 and Psmc4 through the generation of gene targeted mice. Both Psmc3- and
      Psmc4-deficient mice died before implantation, displaying defective blastocyst
      development. These findings indicate that Psmc3 and Psmc4 have similar and
      essential roles in early embryogenesis and further that both ATPases have
      noncompensatory functions in vivo.

PMID- 10945465
TI  - Molecular cloning and characterization of two novel retinoic acid-inducible
      orphan G-protein-coupled receptors (GPRC5B and GPRC5C).
AB  - Using homology searching of public databases with a metabotropic glutamate
      receptor sequence from Caenorhabditis elegans, two novel protein sequences (named
      RAIG-2 (HGMW-approved symbol GPRC5B) and RAIG-3 (HGMW-approved symbol GPRC5C)
      were identified containing seven putative transmembrane domains characteristic of
      G-protein-coupled receptors (GPCRs). RAIG-2 and RAIG-3 encode open reading frames
      of 403 and 442 amino acid polypeptides, respectively, and show 58% similarity to
      the recently identified retinoic acid-inducible gene-1 (RAIG-1, HGMW-approved
      symbol RAI3). Analysis of the three protein sequences places them within the type
      3 GPCR family, which includes metabotropic glutamate receptors, GABA(B)
      receptors, calcium-sensing receptors, and pheromone receptors. However, in
      contrast to other type 3 GPCRs, RAIG-1, RAIG-2, and RAIG-3 have only short N
      terminal domains. RAIG-2 and RAIG-3 cDNA sequences were cloned into the mammalian
      expression vector pcDNA3 with c-myc or HA epitope tags inserted at their N
      termini, respectively. Transient transfection experiments in HEK239T cells using
      these constructs demonstrated RAIG-2 and RAIG-3 expression at the cell surface.
      Distribution profiles of mRNA expression obtained by semiquantitative Taq-Man PCR
      analysis showed RAIG-2 to be predominantly expressed in human brain areas and
      RAIG-3 to be predominantly expressed in peripheral tissues. In addition,
      expression of RAIG-2 and RAIG-3 mRNA was increased following treatment with all
      trans-retinoic acid in a manner similar to that previously described for RAIG-1.
      Finally, RAIG-2 was mapped to chromosome 16p12 (D16S405-D16S3045) and RAIG-3 to
      chromosome 17q25 (D17S1352-D17S785). These results suggest that RAIG-1, RAIG-2,
      and RAIG-3 represent a novel family of retinoic acid-inducible receptors, most
      closely related to the type 3 GPCR subfamily, and provide further evidence for a
      linkage between retinoic acid and G-protein-coupled receptor signal transduction
      pathways.

PMID- 10945466
TI  - A novel candidate gene for mouse and human preaxial polydactyly with altered
      expression in limbs of Hemimelic extra-toes mutant mice.
AB  - Polydactyly is a common malformation of vertebrate limbs. In humans a major locus
      for nonsyndromic pre-axial polydactyly (PPD) has been mapped previously to 7q36.
      The mouse Hemimelic extra-toes (Hx) mutation maps to a homologous chromosome
      segment and has been proposed to affect a homologous gene. To understand the
      molecular changes underlying PPD, we used a positional cloning approach to
      identify the gene or genes disrupted by the Hx mutation and a closely linked limb
      mutation, Hammertoe (Hm). High resolution genetic mapping identified a small
      candidate interval for the mouse mutations located 1.2 cM distal to the Shh
      locus. The nonrecombinant interval was completely cloned in bacterial artificial
      chromosomes and searched for genes using a combination of exon trapping, sample
      sequencing, and mapping of known genes. Two novel genes, Lmbr1 and Lmbr2, are
      entirely within the candidate interval we defined genetically. The open reading
      frame of both genes is intact in mutant mice, but the expression of the Lmbr1
      gene is dramatically altered in developing limbs of Hx mutant mice. The
      correspondence between the spatial and temporal changes in Lmbr1 expression and
      the embryonic onset of the Hx mutant phenotype suggests that the mouse Hx
      mutation may be a regulatory allele of Lmbr1. The human ortholog of Lmbr1 maps
      within the recently described interval for human PPD, strengthening the
      possibility that both mouse and human limb abnormalities are due to defects in
      the same highly conserved gene.

PMID- 10945467
TI  - Refinement of the smallest commonly deleted segment of chromosome 20 in malignant
      myeloid diseases and development of a PAC-based physical and transcription map.
AB  - A deletion of the long arm of chromosome 20, del(20q), is a recurring abnormality
      in malignant myeloid diseases. In previous studies, we delineated a commonly
      deleted segment (CDS) of 5 Mb within band 20q12 flanked by D20S206 (proximal) and
      D20S481 (distal). We have generated a detailed physical map of P1 artificial
      chromosome (PAC) clones of this interval as well as a transcriptional map. The
      contig consists of 81 clones to which 152 markers (27 genes, 45 unique expressed
      sequence tags (ESTs) or UniGenes, 24 polymorphisms, and 56 sequence-tagged sites)
      have been mapped. Using PAC clones for fluorescence in situ hybridization
      analysis of myeloid leukemia cells with reciprocal translocations of 20q, or
      unbalanced rearrangements leading to loss of 20q, we have narrowed the CDS to an
      approximately 250-kb interval encompassing two overlapping PACs, P201E16 and
      P29M7 (between EST AA368224 and D20S481). This interval is gene-rich and contains
      5 characterized genes, 4 UniGenes, and 9 single ESTs. The development of a
      transcriptional map and the identification of the smallest CDS will facilitate
      the molecular cloning of a myeloid leukemia suppressor gene on 20q.

PMID- 10945468
TI  - cDNA cloning and expression analysis of new members of the mammalian F-box
      protein family.
AB  - F-box proteins are critical components of the SCF ubiquitin-protein ligase
      complex and are involved in substrate recognition and recruitment for
      ubiquitination and consequent degradation by the proteasome. We have isolated
      cDNAs encoding a further 10 mammalian F-box proteins. Five of them (FBL3 to FBL7)
      share structural similarities with Skp2 and contain C-terminal leucine-rich
      repeats. The other 5 proteins have different putative protein-protein interaction
      motifs. Specifically, FBS and FBWD4 proteins contain Sec7 and WD40-repeat
      domains, respectively. The C-terminal region of FBA shares similarity with
      bacterial protein ApaG while FBG2 shows homology with the F-box protein NFB42.
      The marked differences in F-box gene expression in human tissues suggest their
      distinct role in ubiquitin-dependent protein degradation.

PMID- 10945469
TI  - Molecular cloning, tissue distribution, and chromosomal mapping of the human
      epithelial Ca2+ channel (ECAC1).
AB  - Functional and morphological analyses indicated that the epithelial Ca2+ channel
      (ECaC), which was recently cloned from rabbit kidney, exhibits the defining
      properties for being the gatekeeper in transcellular Ca2+ (re)absorption. Its
      human homologue provides, therefore, a molecular basis for achieving a better
      understanding of Ca2+ mal(re)absorption. By applying the RACE technique, the full
      length cDNA of human ECaC (HGMW-approved symbol ECAC1) was obtained. It consisted
      of 2,772 bp with an open reading frame of 2,187 bp encoding a protein of 729
      amino acids with a predicted molecular mass of 83 kDa. Phylogenetic analysis
      indicated that this highly selective Ca2+ channel exhibits a low level of
      homology (<30%) to other Ca2+ channels, suggesting that it belongs to a new
      family. hECaC was highly expressed in kidney, small intestine, and pancreas, and
      less intense expression was detected in testis, prostate, placenta, brain, colon,
      and rectum. These ECaC-positive tissues also expressed the 1,25-dihydroxyvitamin
      D3-sensitive calcium-binding proteins, calbindin-D9K and/or calbindin-D28K. The
      human ECaC gene mapped to chromosome 7q31.1-q31.2. Taken together, the
      conspicuous colocalization of hECaC and calbindins in organs that are not prime
      regulators of plasma Ca2+ levels could illustrate new pathways in cellular Ca2+
      homeostasis.

PMID- 10945470
TI  - MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia.
AB  - Oncogenic hypophosphatemic osteomalacia (OHO) is characterized by a renal
      phosphate leak, hypophosphatemia, low-serum calcitriol (1,25-vitamin-D3), and
      abnormalities in skeletal mineralization. Resection of OHO tumors results in
      remission of the symptoms, and there is evidence that a circulating phosphaturic
      factor plays a role in the bone disease. This paper describes the
      characterization and cloning of a gene that is a candidate for the tumor-secreted
      phosphaturic factor. This new gene has been named MEPE (matrix extracellular
      phosphoglycoprotein) and has major similarities to a group of bone-tooth mineral
      matrix phospho-glycoproteins (osteopontin (OPN; HGMW-approved symbol SPP1),
      dentin sialo phosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone
      sialoprotein II (IBSP), and bone morphogenetic proteins (BMP). All the proteins
      including MEPE contain RGD sequence motifs that are proposed to be essential for
      integrin-receptor interactions. Of further interest is the finding that MEPE,
      OPN, DSPP, DMP1, IBSP, and BMP3 all map to a defined region in chromosome 4q.
      Refined mapping localizes MEPE to 4q21.1 between ESTs D4S2785 (WI-6336) and
      D4S2844 (WI-3770). MEPE is 525 residues in length with a short N-terminal signal
      peptide. High-level expression of MEPE mRNA occurred in all four OHO tumors
      screened. Three of 11 non-OHO tumors screened contained trace levels of MEPE
      expression (detected only after RT-PCR and Southern 32P analysis). Normal tissue
      expression was found in bone marrow and brain with very-low-level expression
      found in lung, kidney, and human placenta. Evidence is also presented for the
      tumor secretion of clusterin (HGMW-approved symbol CLU) and its possible role as
      a cytotoxic factor in one of the OHO patients described.

PMID- 10945471
TI  - Chromosomal location and genomic structure of the human translin-associated
      factor X gene (TRAX; TSNAX) revealed by intergenic splicing to DISC1, a gene
      disrupted by a translocation segregating with schizophrenia.
AB  - Two candidate genes, DISC1 and DISC2 on chromosome 1, are disrupted by a
      translocation that segregates with major psychiatric illness. Several DISC1
      transcripts contain TRAX (HGMW-approved symbol TSNAX) sequence at the 5' end.
      These transcripts initiate at the 5' end of TRAX and terminate at the final exon
      of DISC1. Five species of transcript resulting from intergenic splicing have been
      identified; one encodes a novel TRAX/DISC1 fusion protein. The remaining four
      transcripts are bicistronic and encode a series of novel truncated isoforms of
      TRAX and DISC1. Demonstration that the various TRAX/DISC1 transcripts are
      translated awaits further experimentation. As a consequence of the observation of
      intergenic splicing, the human TRAX gene has been mapped at least 35 kb proximal
      to DISC1 and within approximately 150-250 kb of the translocation breakpoint at
      1q42.1. The TRAX gene consists of six exons with a putative CpG island at the 5'
      end. Four major transcripts are produced from this gene, of which the smallest,
      at 2.7 kb, had previously been identified.

PMID- 10945472
TI  - Isolation and preliminary characterization of the human and mouse homologues of
      the bacterial cell cycle gene era.
AB  - Era is an essential GTPase that is required for proper cell cycle progression and
      cell division in Escherichia coli and is found in nearly all bacteria sequenced
      to date. To determine whether Era is also present in eukaryotic organisms, we
      searched the dbEST database and found EST clones coding for proteins that were
      similar to Era. Full sequencing of these ESTs from human and mouse identified a
      conserved homologue, ERAL1 (Era-like 1). ERAL1 maps to 17q11.2 in human and is
      located in the syntenic region of mouse chromosome 11. ERAL1 may be an attractive
      candidate for a tumor suppressor gene since ERAL1 is located in a chromosomal
      region where loss of heterozygosity is often associated with various types of
      cancer.

PMID- 10945473
TI  - Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein
      phosphatase 2A, PPP2R2C, to human chromosome 4p16.
AB  - Protein phosphatase 2A (PP2A) is one kind of serine/ threonine protein
      phosphatase regulating mainly cell growth and division. It comprises three
      subunits, A, B, and C. The B-subunit is involved in enzyme activity and substrate
      specificity. The B-subunit family is of great diversity and is divided into three
      classes, the B1, B2, and B3 subfamilies. Until now, two members of the B1
      subfamily, B1alpha and B1beta, have been identified in human. In this report, the
      third member of the sub-family, B1gamma, was identified, and its cDNA was
      isolated from a human brain cDNA library. This novel cDNA is 4,120 bp in length
      and contains an open reading frame (nt 55-1,398) encoding 447 amino acid
      residues. The putative protein shares 81 and 85% identity with B1alpha (PPP2R2A)
      and B1beta (PPP2R2B), respectively, and was named PPP2R2C for its high level of
      homology to the other two isoforms. One remarkable characteristic of this novel
      gene is that it is highly expressed in brain with a 4.7-kb transcript while it is
      nearly undetectable in other tissues. In addition, the PPP2R2C gene was localized
      to human chromosome 4p16 between markers D4S2925 and D4S3007 with 5.45 cR (LOD >
      14) and 2.63 cR (LOD > 15) RH distance, respectively, by radiation hybrid panel
      mapping.

PMID- 10945474
TI  - Genomic construct and mapping of the gene for CMAP (leukocystatin/cystatin F,
      CST7) and identification of a proximal novel gene, BSCv (C20orf3).
AB  - It is proposed that CMAP (leukocystatin/cystatin F, HGMW-approved symbol CST7)
      expression is correlated with the metastatic potential of malignant tumors. FISH
      analysis of human and murine CMAP revealed the genomic loci 20p11.21-p11.22 of
      the human family 2 cystatin cluster and mouse chromosome region 2G1-G3,
      respectively. Like murine CMAP, the human CMAP gene is constructed from four
      divided exons, all of which encode the functional domains of the putative
      translational product. Based on the computational analysis, a novel gene weakly
      similar to the plant strictosidine synthase, named BSCv (HGMW-approved symbol
      C20orf3), was identified on the opposite allele at a distance of a few kilobases
      from the human CMAP gene. In between human CMAP and the BSCv gene, there is a
      unique tandem repeat sequence. CpG-rich island characteristics and GC-box
      features normally observed in housekeeping genes were not seen around exon 1 of
      the CMAP gene, reflecting the restricted expression of CMAP in hematopoietic
      cells.

PMID- 10945475
TI  - Virtual cloning and physical mapping of a human T-box gene, TBX4.
AB  - The Tbx2/3/4/5 subfamily is one of the largest subgroupings within the T-box gene
      family, the members of which encode developmentally critical transcription
      factors. TBX4, a human member of the Tbx2/3/4/5 subfamily, has been identified
      and characterized from a high-throughput genomic sequence. The genomic
      organization of TBX4 was elucidated by computational sequence analysis, and the
      putative cDNA sequence was assembled. The genomic organization of TBX4 is very
      similar to that of TBX5, as is the situation for TBX2 and TBX3. The physical
      configuration of the TBX4-TBX2 cluster on human chromosome 17q21-q22 is similar
      to that of the TBX5-TBX3 cluster on chromosome 12q23-q24. The assembled TBX4 cDNA
      sequence was searched against the EST databases, and a TBX4 EST was identified.

PMID- 10945476
TI  - High-resolution physical and transcript map of the locus for venous malformations
      with glomus cells (VMGLOM) on chromosome 1p21-p22.
AB  - Vascular anomalies are congenital lesions that usually occur sporadically, but
      can be inherited. Previously, we have described that venous malformations,
      localized bluish-purple skin lesions, are caused by an activating mutation in the
      TIE2/TEK receptor. Moreover, we mapped another locus to chromosome 1p21-p22, for
      venous malformations with glomus cells (VM-GLOM). Here we report a physical map,
      based on 18 overlapping YAC clones, spanning this 5-Mb VMGLOM locus, from marker
      GATA63C06 to D1S2664. In addition, we report a sequence-ready PAC map of 46
      clones covering 1.48 Mb within the YAC contig, a region to which we have
      restricted VMGLOM. We describe 21 new STSs and nine novel CA repeats, seven of
      which are polymorphic. These data will enable positional cloning of genes for
      diseases mapped to this locus, including the VMGLOM gene, likely a currently
      unknown regulator of vasculogenesis and/or angiogenesis.

PMID- 10945477
TI  - Centromere-linked microsatellite markers for linkage groups 3, 4, 6, 7, 13, and
      20 of zebrafish (Danio rerio).
AB  - A large number of interesting mutations affecting development and organogenesis
      have been identified through genetic screens in zebrafish. Mapping of these
      mutations to a chromosomal region can be rapidly accomplished using half-tetrad
      analysis. However, knowledge of centromere-linked markers on every chromosome is
      essential to this mapping method. Centromeres on all 25 linkage groups have been
      mapped on the RAPD zebrafish genetic map. However, species specificity and the
      lack of codominance make RAPD markers less practical for mapping than
      microsatellite-based markers. On the microsatellite-based genetic map, centromere
      linked markers have been identified for 19 linkage groups. No direct evidence has
      been published linking microsatellite markers to the centromeres of linkage
      groups 3, 4, 6, 7, 13, and 20. Therefore, we compared the microsatellite-based
      genetic map with the RAPD map to identify markers most likely linked to the
      centromeres of these 6 linkage groups. These candidate markers were tested for
      potential centromere linkage using four panels of half-tetrad embryos derived by
      early-pressure treatment of eggs from four different female zebrafish. We have
      identified microsatellite markers for linkage groups 3, 4, 6, 7, 13, and 20 to
      within 1.7 cM of their centromeres. These markers will greatly facilitate the
      rapid mapping of mutations in zebrafish by half-tetrad analysis.

PMID- 10945478
TI  - Comments on nomenclature of TOM genes/proteins and characterization of psi4Tom20,
      a novel processed pseudogene of the human Tom20 gene.

PMID- 10945479
TI  - Fungal degradation of aflatoxin B1.
AB  - A number of fungal cultures were screened to select an organism suitable to be
      used in the detoxification of aflatoxin B1. They were co-cultured in Czapek-Dox
      Casamino acid medium with aflatoxin B1 producing Aspergillus flavus. Several
      fungal cultures were found to prevent synthesis of aflatoxin B1 in liquid culture
      medium. Among these Phoma sp., Mucor sp., Trichoderma harzianum, Trichoderma sp.
      639, Rhizopus sp. 663, Rhizopus sp. 710, Rhizopus sp. 668, Alternaria sp. and
      some strains belonging to the Sporotrichum group (ADA IV B14(a), ADA SF VI BF
      (9), strain 720) could inhibit aflatoxin synthesis by > or =90%. A few fungi,
      namely ADA IV B1, ADA F1, ADA F8, also belonging to the Sporotrichum group, were
      less efficient than the Phoma sp. The Cladosporium sp. and A. terreus sp. were by
      far the least efficient, registering <10% inhibition. The cultures which prevent
      aflatoxin biosynthesis are also capable of degrading the preformed toxin. Among
      these, Phoma sp. was the most efficient destroying about 99% of aflatoxin B1. The
      cell free extract of Phoma sp. destroyed nearly 50 microg aflatoxin B1 100 ml(-1)
      culture medium (90% of the added toxin), and this was more effective than its own
      culture filtrate over 5 days incubation at 28+/-2 degrees C. The degradation was
      gradual: 35% at 24 h, 58% at 48 h, 65% at 72 h, 85% at 96 h and 90% at 120 h. The
      possibility of a heat stable enzymatic activity in the cell free extract of Phoma
      is proposed.

PMID- 10945480
TI  - Complexation and ionophoric properties of taxol and colchicine: complex formation
      and transport of sodium, potassium, magnesium and calcium ions across a liquid
      membrane.
AB  - We report the activities of taxol (an anticancer drug) and colchicine, which are
      inhibitors of microtubule organization, on the complexation and transport of Na+,
      K+, Mg2+ and Ca2+ ions across a liquid membrane, using a spectrophotometric
      procedure. Taxol, a diterpenoid compound, that has been demonstrated to possess a
      potent antitumour activity, is shown to extract Na+, K+, Mg2+ and Ca2+ ions from
      the aqueous solution to the organic phase with preference for Ca2+ ions. A
      kinetic study of the transport and complexation of Na+, K+, Mg2+ and Ca2+ ions
      through a liquid membrane revealed that the K+ ion is more rapidly transported
      and the Ca2+ ion is more rapidly complexed than other ions. However, colchicine,
      another alkaloid compound, extracted and transported only the divalent ions
      tested, Mg2+ and Ca2+. In both complexation and transport, the flux of the ions
      increases with the concentration of taxol or colchicine. Complexation and
      ionophoric properties of taxol and colchicine sheds new lights on therapeutic
      properties of these drugs. The treatment of disease states by the administration
      of these drugs to alter membrane permeability will prove to be a valuable
      therapeutic concept.

PMID- 10945481
TI  - Effects of endotoxin and tumor necrosis factor alpha on regional brain
      neurotransmitters in mice.
AB  - Alterations in regional brain concentration of dopamine (DA), norepinephrine
      (NE), serotonin (5-HT) and their metabolites were investigated in male BALB/c
      mice injected intraperitoneally with bacterial lipopolysaccharide (LPS, 2 mg kg(
      1)) or recombinant murine tumor necrosis factor alpha (TNFalpha, 0.1 mg kg(-1))
      at 2, 6, 12 and 24 h after the injection. At 2 h post-injection the LPS
      administration resulted in hypothermia, which was not apparent at later time
      points. No consistent effects were observed by either LPS or TNFalpha on
      peripheral leukocyte counts or plasma transaminase levels. Both LPS and TNFalpha
      slightly elevated NE metabolism in the striatum at 2-12 h. Concentrations of DA
      and its metabolites were significantly elevated only in the hypothalamus
      following TNFalpha at 24 h. Tumor necrosis factor alpha exerted pronounced
      effects on 5-HT metabolism in most brain regions at 2 h. Results suggest that the
      effect of LPS is more complex compared with TNFalpha because of the endogenous
      production of other cytokines including the TNFalpha.

PMID- 10945482
TI  - Spirolide composition of micro-extracted pooled cells isolated from natural
      plankton assemblages and from cultures of the dinoflagellate Alexandrium
      ostenfeldii.
AB  - A novel micro-extraction technique was applied to the extraction of biologically
      active macrocyclic imines known as spirolides from pooled individual cells
      isolated from spirolide-rich plankton material. For comparison, this method was
      also applied to pooled individual cells isolated from a unialgal culture of the
      marine dinoflagellate Alexandrium ostenfeldii (Paulsen) Balech & Tangen, a
      species known to produce spirolides. Both athecate cells and motile forms of
      gonyaulacoid dinoflagellates derived from size-fractionated plankton material
      from Nova Scotia, Canada were sorted and pooled by the glass micropipette
      isolation technique and by flow cytometry. The development of a highly sensitive
      analytical method for spirolides (detection limit 2 ng ml(-1) for spirolide B)
      using liquid chromatography-mass spectrometry (LC-MS) and application to micro
      extracted samples allowed the accurate determination of spirolide composition in
      as few as 50 cells. Total spirolide concentrations (fmol cell(-1)) calculated
      from pooled micropipette isolated cells were very consistent with those based
      upon bulk- or micro-extractions of A. ostenfeldii cells from unialgal batch
      cultures in exponential growth phase. The results of the pooled cell selection
      from field material from two sites in Nova Scotia confirmed the association of
      spirolides with vegetative cells of A. ostenfeldii and related athecate forms.
      Combining these techniques represents a highly sensitive method for the analysis
      of marine toxins within complex plankton matrices, even when the toxigenic
      species is in low abundance, by enrichment of the target organism.

PMID- 10945483
TI  - Coupling of saxitoxin biosynthesis to the G1 phase of the cell cycle in the
      dinoflagellate Alexandrin fundyense: temperature and nutrient effects.
AB  - The correlation between changes in length of the different cell cycle stages and
      the toxicity of Alexandrium fundyense Balech was studied in semi-continuous
      cultures. Growth rates ranging from 0.031 d(-1) to 0.36 d(-1) were established at
      different temperatures or levels of phosphate limitation. In all treatments, G1
      was the phase with the longest duration. Decrease in growth rate was associated
      with an increase in duration of the different cell cycle stages. Toxin content
      was always directly correlated to the duration of the G1 phase. In both the
      temperature treatments and the phosphate limitation experiments, toxin production
      rates remained constant for the respective range of conditions, implying that the
      variations in toxin content observed were a result of increasing periods of
      biosynthetic activity. Toxin accumulation was directly correlated to protein
      biosynthesis in all temperature treatments. In contrast, toxin content showed
      little correlation with protein content as phosphate limitation increased.
      Significant differences in toxin composition were observed between the
      temperature and phosphate treatments. Total concentrations of GTX II and III and
      C I and II were significantly higher in the phosphate-limited cultures, while the
      levels of STX, NEO and gonyautoxins I and IV remained virtually unchanged. We
      conclude that toxin biosynthesis in A. fundyense is coupled to the G1 phase of
      the cell cycle, that toxin synthesis is not down-regulated by phosphate
      deprivation and that interconversions among saxitoxin derivatives are influenced
      by the availability of phosphate.

PMID- 10945484
TI  - Performance and standards for the process of head and neck cancer care: South and
      West audit of head and neck cancer 1996-1997 (SWAHN I). South and West Regional
      Cancer Organisation Tumour Panel for Head and Neck Cancer.
AB  - Evidence suggests wide variation in cancer care between different hospitals in
      the UK. To establish bench-marking data, we designed a prospective, 1 year
      regional study comparing key performance measures with established standards for
      the 28 hospital Trusts in the South and West of England involved in head and neck
      cancer care. 566 sequential patients with a newly-diagnosed head and neck cancer
      were included. Numbers referred and treated per hospital Trust were 1-58 and 1-65
      respectively. 59% of patients received a pretreatment chest X-ray (standard 95%).
      45% of patients were seen in a multidisciplinary clinic pretreatment (standard
      95%), and this was proportional to the frequency of clinics held (P<0.0001).
      Median number of cases treated per surgeon was 4 (1-26), and by radiotherapist
      was 10 (1-51). Times between parts of the process of oral cancer care were closer
      to the standards than those for laryngeal cancer. Two patients were entered into
      a clinical trial. One had a quality-of-life score. Thus, in 1996-1997, in the
      South and West of England, there were major discrepancies between actual
      performance and established standards in many fundamental aspects of head and
      neck cancer care. Re-audit is essential to determine if the implementation of the
      Calman-Hine report has resulted in improvements.

PMID- 10945485
TI  - Improving the outcome of salvage treatment for non-seminomatous germ cell tumours
      (NSGCT).
AB  - Between 1991-96, 41 patients were treated in this unit for relapsed non
      seminomatous germ cell tumours (NSGCT). Twenty-eight patients had raised markers
      at relapse: 17 required salvage chemotherapy and post-chemotherapy surgery, 11
      only chemotherapy. In addition 9 patients received high dose chemotherapy.
      Overall 16/28 patients (57%) requiring chemotherapy remain alive, 14 (50%)
      disease free. Of the 17 patients treated with chemotherapy and surgery: 12 remain
      alive, 10 (59%) with no evaluable disease. Only 4/11 (36%) patients treated with
      chemotherapy alone remain alive, all in complete remission (CR). For relapse with
      raised markers, univariate analysis suggests that less than CR to induction
      therapy, resulting in the presence of residual disease is the most important
      predictor of poor outcome (P<0.001). All of the 13 patients relapsing with normal
      markers remain alive, having been primarily treated surgically. Overall these
      results indicate an improving outlook for relapsed NSGCT.

PMID- 10945486
TI  - Prognostic factors for tumour response, progression-free survival and toxicity in
      metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line
      chemotherapy after 5FU failure. CPT-11 F205, F220, F221 and V222 study groups.
AB  - Our purpose was to determine, in patients with metastatic colorectal carcinoma
      treated with irinotecan single-agent after 5-FU failure, the most significant
      predictive parameters for tumour response, progression-free survival and
      toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant
      metastatic colorectal carcinoma entered four consecutive phase II trials. The
      first two studies assessed tumour response, the other two were randomized studies
      which assessed the efficacy of racecadotril to prevent irinotecan-induced
      diarrhoea. Due to homogeneous main eligibility criterias, data from those studies
      could be pooled for statistical analysis. Potential clinical and biological
      predictive factors (PF) for toxicity, tumour growth control, e.g. response or
      stabilization and progression-free survival (PFS), were studied in multivariate
      analysis. 363 patients were evaluable for response, 432 were evaluable for PFS,
      368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline
      haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or
      4 neutropenia or diarrhoea at first cycle and a low number of organs involved
      were the most PF for tumour growth control (P<0.05). Significant prognostic
      variables for PFS were WHO Performance Status, liver and lymph-node involvement,
      time since diagnosis, age and CEA value (P < or =0.02). Six groups of patients
      based on the number of unfavourable prognostic factors are presented. Baseline
      bilirubin, haemoglobin level, number of organs involved and time from diagnosis
      were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU
      progression and prior abdominopelvic irradiation were PF for delayed diarrhoea
      (P< or =0.05). These PF should help clinicians to anticipate for a given patient
      the probability to observe a response/stabilization or a toxicity. These results
      should also be prospectively confirmed in ongoing or future trials using
      irinotecan, both as a single agent and in combination with other drugs.

PMID- 10945487
TI  - A phase II trial of paclitaxel and epirubicin in advanced breast cancer.
AB  - Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded
      high response rates but significant cardiac toxicity was observed. In this phase
      II trial we investigated the efficacy and safety of paclitaxel combined with
      epirubicin. Patients with advanced breast cancer, performance status 0-2,
      measurable disease, and a normal left ventricular ejection fraction, who may have
      received adjuvant chemotherapy were treated with epirubicin 75 mg m(-2) followed
      by a 3-h infusion of paclitaxel 175 mg m(-2) repeated every 3 weeks. Forty-three
      eligible patients were treated at six centres. 67% patients received the maximum
      of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR.
      Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and
      estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four
      patients had a decrease in the left ventricular ejection fraction (LVEF) of > or
      =20% of baseline value, and in two patients the LVEF decreased to below the lower
      limit of normal, but no patient developed clinical evidence of cardiac failure.
      Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were
      complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was
      uncommon. In conclusion, paclitaxel 175 mg m(-2) and epirubicin 75 mg m(-2) is a
      well tolerated, promising regimen for the treatment of advanced breast cancer.

PMID- 10945488
TI  - Anti-GnRH antibodies can induce castrate levels of testosterone in patients with
      advanced prostate cancer.
AB  - D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of
      this pilot study was to assess the tolerance of D17DT and the production of anti
      GnRH antibodies from two doses, 30 and 100 microg, in patients with locally
      advanced prostate cancer. Twelve patients with histologically proven prostate
      cancer in whom hormonal therapy was indicated were recruited. Patients received
      either 30 or 100 microg given intramuscularly on three separate occasions over
      six weeks. Patients were followed up and blood was taken for estimation of serum
      testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well
      tolerated. In 5 patients a significant reduction in serum testosterone and PSA
      was seen. Castrate levels of testosterone were achieved in 4 and maintained for
      up to 9 months. Patients with the highest antibody titre had the best response in
      terms of testosterone suppression. This study shows that it is possible to
      immunize a patient with prostate cancer against GnRH to induce castrate levels of
      testosterone. This state appears to be reversible. This novel form of
      immunotherapy may have advantages over conventional forms of hormonal therapy and
      further studies are warranted in order to try and increase the proportion of
      responders.

PMID- 10945489
TI  - Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell
      lung cancer--a randomized trial with quality of life as the primary outcome. UK
      NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.
AB  - Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not
      requiring immediate radiotherapy were enrolled into this randomized multicentre
      trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine
      received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six
      cycles. The main aim of this trial was to compare patient assessment of a
      predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and
      LC13 scales. The primary end-points were defined as (1) the percentage change in
      mean SS14 score between baseline and 2 months and (2) the proportion of patients
      with a marked (> or = 25%) improvement in SS14 score between baseline and 2
      months sustained for > or =4 weeks. The secondary objectives were to compare
      treatments with respect to overall survival, and multidimensional QL parameters.
      The treatment groups were balanced with regard to age, gender, Karnofsky
      performance status (KPS) and disease stage (40% had metastatic disease). The
      percentage change in mean SS14 score from baseline to 2 months was a 10% decrease
      (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e.
      deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or =
      4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher
      proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P
      = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed
      greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the
      BSC arm (one symptom item). There was greater deterioration in the BSC alone arm
      (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour
      response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no
      difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for
      gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84)
      for BSC patients, and 1 -year survival was 25% for gemcitabine + BSC and 22% for
      BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients
      received palliative radiotherapy. The median time to radiotherapy was 29 weeks
      for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with
      gemcitabine + BSC reported better QL and reduced disease-related symptoms
      compared with those receiving BSC alone. These improvements in patient-assessed
      QL were significant in magnitude and were sustained.

PMID- 10945490
TI  - Importance of extensive staging in patients with mucosa-associated lymphoid
      tissue (MALT)-type lymphoma.
AB  - Lymphoma of the mucosa-associated lymphoid tissue (MALT) type usually arises in
      MALT acquired through chronic antigenic stimulation triggered by persistent
      infection and/or autoimmune processes. Due to specific ligand-receptor
      interactions between lymphoid cells and high-endothelial venules of MALT, both
      normal and neoplastic lymphoid cells display a pronounced homing tendency to MALT
      throughout the body. In the case of neoplastic disease these homing properties
      may be responsible for lymphoma dissemination among various MALT-sites. According
      to this concept, we have standardized staging procedures in all patients
      diagnosed with MALT-type lymphoma. All patients with MALT-type lymphoma underwent
      standardized staging procedures before treatment. Staging included ophthalmologic
      examination, otolaryngologic investigation, gastroscopy with multiple biopsies,
      endosonography of the upper gastrointestinal tract, enteroclysis, colonoscopy,
      computed tomography of thorax and abdomen and bone marrow biopsy. Biopsy was
      performed in all lesions suggestive for lymphomatous involvement, and evaluation
      of all biopsy specimens was performed by a reference pathologist. 35 consecutive
      patients with histologically verified MALT-type lymphoma were admitted to our
      department. Twenty-four patients (68%) had primary involvement of the stomach,
      five (15%) had lymphoma of the ocular adnexa, three (8.5%) had lymphoma of the
      parotid, and three (8,5%) of the lung. Lymph-node involvement corresponding to
      stage EII disease was found in 13 patients (37%), only one patient with primary
      gastric lymphoma had local and supradiaphragmatic lymph-node involvement (stage
      EIII). Bone marrow biopsies were negative in all patients. Overall, eight of 35
      patients (23%) had simultaneous biopsy-proven involvement of two MALT-sites: one
      patient each had lymphoma of parotid and lacrimal gland, conjunctiva and
      hypopharynx, conjunctiva and skin, lacrimal gland and lung, stomach and colon,
      and stomach and lung. The remaining two patients had bilateral parotideal
      lymphoma. Staging work-up was negative for lymph-node involvement in all of these
      eight patients. The importance of extensive staging in MALT-type lymphoma is
      emphasized by the demonstration of multiorgan involvement in almost a quarter of
      patients. In addition, our data suggest that extra-gastrointestinal MALT-type
      lymphoma more frequently occurs simultaneously at different anatomic sites than
      MALT-type lymphoma involving the GI-tract.

PMID- 10945491
TI  - A phase II study of paclitaxel, weekly, 24-hour continous infusion 5
      fluorouracil, folinic acid and cisplatin in patients with advanced gastric
      cancer.
AB  - To evaluate the toxicity and efficacy of combination chemotherapy with
      paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in
      patients (pts) with unresectable, locally advanced or metastatic gastric
      adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a
      median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly
      over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel
      175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50
      mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22,
      29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles
      (range 1-4) were administered to 45 pts assessable for response, survival and
      toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI:
      35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the
      site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%)
      were considered to have failed treatment, 8 pts (18%) due to progressive disease
      and 5 pts (11%) who did not receive one complete cycle of therapy due to acute
      non-haematologic toxicity. The median progression-free and overall survival times
      were 9 months (range 1-36+) and 14 months (range 2-36+), respectively.
      Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade
      IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included
      nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each
      (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly
      due to neutropenia. All pts were treated on an outpatient basis. The combination
      of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be
      a highly active regimen for the treatment of pts with advanced gastric cancer.
      While the overall acceptable toxicity allows its use in the palliative setting,
      it may also be an attractive option to be tested for neoadjuvant or adjuvant
      treatment.

PMID- 10945492
TI  - The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer
      patients in Israel.
AB  - Inherited predisposition occurs in 5-10% of all prostate cancer (CaP) patients,
      but the genes involved in conferring genetic susceptibility remain largely
      unknown. Several lines of evidence indicate that germline mutations in BRCA1 and
      BRCA2 might be associated with an increased risk for CaP. Three mutations in
      these two genes (185delAG and 5382InsC (BRCA1) and 6174delT (BRCA2) occur in
      about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation,
      in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these
      germline mutations to prostate cancer in Jewish Israeli patients, we tested 174
      unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations
      by PCR amplification and modified restriction enzyme digests. Patient's age range
      was 45-81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to
      55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second
      degree relative with CaP or breast cancer, respectively. Overall, five mutation
      carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158
      (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55,
      and only one of them had a family history of breast and CaP. In addition, no
      allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family
      history of CaP, using seven microsatellite markers. We conclude that the rate of
      the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not
      significantly differ from that of the general population, and that mutational
      inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2
      mutations probably contribute little to CaP occurrence, to inherited
      predisposition, and to early onset disease in Jewish individuals.

PMID- 10945493
TI  - Genomic alterations associated with loss of heterozygosity for TP53 in Li
      Fraumeni syndrome fibroblasts.
AB  - Studies of Li-Fraumeni syndrome fibroblasts heterozygous for germline TP53
      mutations have shown that loss of heterozygosity (LOH) occurs during passaging
      and is associated with genomic instability, such as chromosomal aberrations and
      aneuploidy to investigate the genomic changes associated with LOH in Li-Fraumeni
      (LF) fibroblasts, we have analysed cell strains at increasing population
      doublings (PD) using Comparative Genomic Hybridization (CGH). We have looked at
      three groups of cell strains: LF mutation-carrying strains which showed LOH for
      TP53, LF mutation-carrying strains which did not show LOH, and strains from
      normal individuals. Using CGH, we have detected loss of distinct chromosomal
      regions associated with LOH in 4 out of 5 mutation-carrying strains. In
      particular we have found loss of chromosomal regions containing genes involved in
      cell cycle control or senescence, including loss of 9p and 17p in these strains.
      Other recurrent changes included loss of chromosomes 4q and 6q, regions shown to
      contain one or more tumour suppressor genes. No genomic alterations were detected
      at cumulative PD in the normal strains or in the LF mutation-carrying strains
      which did not show LOH for TP53. We have also analysed the three groups of
      strains for microsatellite instability and somatic TP53 mutations, and have found
      genetic alterations in only one strain.

PMID- 10945494
TI  - Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation
      of prognosis in potentially curative resected non-small cell lung cancer.
AB  - A prospective study was performed in patients with non-small cell lung cancer
      (NSCLC) to evaluate the prognostic importance of multiple molecular marker (p53,
      c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curative resections
      (RO resection) for NSCLC in histopathological stages I-IIIA were included. SSCP
      analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired
      tumour and normal lung tissue samples and immunohistochemistry (c-erbB-2) was
      done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody.
      46/103 (44.6%) NSCLC showed p53 mutations and 17/103 (16.5%) c-Ki-ras mutations
      including 12/37 (32.4%) adenocarcinomas. Overexpression of c-erbB-2 (p185) was
      detected in 56/103 (54.4%) tumours. 24/103 (23.3%) NSCLC were negative for
      alterations in all 3 parameters (c-Ki-ras, p53 and p185) whereas 79/103 (76.7%)
      were positive for at least one of the 3 parameters. In a regression model
      including a multiple molecular marker parameter (negative for all 3 markers
      versus positive for at least one marker), histopathological stage (P<0.00001),
      respectively the pT (P<0.01) and pN (P<0.00001) categories and the multiple
      molecular marker parameter (P<0.01) were of significant prognostic importance.
      This study demonstrates that testing 3 molecular markers (c-Ki-ras, p53 and c
      erbB-2) improves estimation of prognosis compared to single marker testing and
      appears to define low (82.6%+/-7.9% 5-year survival) and high risk (40.2%+/-5.5%
      5-year survival) groups for treatment failure in potentially curative (RO)
      resected NSCLC.

PMID- 10945495
TI  - Tumour necrosis factor-alpha and transforming growth factor-beta are
      significantly associated with better prognosis in non-small cell lung carcinoma:
      putative relation with BCL-2-mediated neovascularization.
AB  - Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic
      activities of cytokines in the pathogenesis and progression of malignancy. Tumour
      necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta)
      have emerged as two of the many host-derived mediators that seem to interfere
      with both antiproliferative and tumorigenic effects in malignant tumours
      including lung cancer. However, their association with tumour prognosis or
      prognostic factors has not yet been completely clarified. In this study, we
      assessed TNF-alpha and TGF-beta mRNA expression by RT-PCR technique in 61 NSCLC
      samples, demonstrating the presence of TNF-alpha and TGF-beta mRNA in 55.74% and
      45.9% of cases, respectively. We also evaluated the expression of the two
      distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive
      signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we
      evaluated the prognostic impact of the two growth-inhibiting factors using the
      Kaplan-Meier analysis. In the univariate analysis patients without nodal
      metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF
      alpha and TGF-beta positive cancers (P = 0.01 and P = 0.03) showed a favourable
      prognosis in terms of overall survival. Since our previous studies demonstrated a
      significant association between NSCLC behaviour, neoangiogenesis and bcl-2
      expression, we investigated the putative relation between TNF-alpha and TGF-beta
      on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl
      2 protein expression, on the other hand. Our results showed a significant direct
      association between TNF-alpha and bcl-2 (P = 0.05) and an inverse association
      between TNF-alpha and microvessel count (P = 0.03). Moreover, as previously
      demonstrated, we observed a significant inverse correlation between bcl-2 protein
      expression and vascular count (P = 0.05), suggesting that the favourable effect
      of TNF-alpha on clinical outcome may be related to a bcl-2-mediated low
      neovascular development.

PMID- 10945496
TI  - Pathology characteristics that optimize outcome prediction of a breast screening
      trial.
AB  - The ability of pathology characteristics to predict outcome was tested with the
      1029 cancers accumulated in the Edinburgh Randomized Trial of breast screening
      after 14 years follow-up. The majority (55.7%) were in the screening arm, which
      also had more operable cases (81.3% vs 62.2%); the reduction in the proportion of
      inoperable breast cancers in a UK female population invited to mammographic
      screening is a notable effect of the trial. In the 691 operable invasive cases
      the size, histological type, grade, node status and node number group
      individually showed highly significant (P<0.001) association with survival. In
      multivariate analysis the Nottingham Prognostic Index (NPI) derived from these
      features showed highly significant association with survival (P<0.001). However,
      when first adjusted for NPI, combined addition of pathological size in 6
      categories and histological type as special or not had an independent association
      with survival that was statistically firmly based (P<0.001). For operable breast
      cancer the gains are in smaller sizes, better histological features, and higher
      proportion node negative. The weighting factors applied to pathology indicators
      of survival in the NPI are not optimal for a population included in a trial of
      screening. In particular, a linear trend of the index with pathological size is
      not appropriate. Inclusion of histological type as special or not improves the
      index further.

PMID- 10945497
TI  - Monoclonal antibody MA454 reveals a heterogeneous expression pattern of MAGE-1
      antigen in formalin-fixed paraffin embedded lung tumours.
AB  - Cancer/testis (CT) antigens such as those encoded by the MAGE-gene family are
      expressed in a wide variety of malignant neoplasms. In normal tissues, expression
      is generally restricted to testis. Current knowledge of the expression pattern of
      CT antigens is mainly based on mRNA analysis. Little is known about actual
      protein expression. We previously developed MA454, a monoclonal antibody (mAb) to
      MAGE-1 recombinant protein. By employing antigen retrieval techniques, we show
      that MA454 is reactive on formalin-fixed paraffin-embedded tissues.
      Immunohistochemical (IHC) analysis of a normal tissue panel revealed staining
      solely in germ cells of testes. A series of 59 lung tumours was co-typed for MAGE
      1 expression by RT-PCR and by immunohistochemistry with MA454. MA454 was positive
      in 19/59 cases (32%). MAGE-1 mRNA was found in 17 of the 54 cases (32%) available
      for RT-PCR. Of the 19 MA454-reactive tumours, 15 showed a highly heterogeneous
      pattern of expression. The other 4 MA454 positive cases revealed immunoreactivity
      in >25% of tumour areas. Of the 53 cases typed for both, mRNA and protein
      expression, 48 co-typed whereas 5 cases were discrepant, a likely consequence of
      heterogeneous MAGE-1 expression. The predominantly focal expression of MAGE-1
      suggests that this antigen might not be sufficient as a sole target for
      immunotherapeutic approaches.

PMID- 10945498
TI  - Expression of topoisomerase IIIalpha in normal and neoplastic tissues determined
      by immunohistochemistry using a novel monoclonal antibody.
AB  - Topoisomerases are nuclear enzymes that modulate the topological structure of DNA
      in order to facilitate cellular events such as replication and transcription.
      These enzymes are also the cellular targets of certain classes of
      chemotherapeutic agents termed topoisomerase poisons. A new human topoisomerase
      isoform, IIIa, was discovered in 1996, which is thought to have roles in genome
      stability and possibly chromosome separation during mitosis. It is possible that
      novel or existing anti-topoisomerase agents target topoisomerase IIIa, suggesting
      that this enzyme may have potential as a prognostic marker and chemotherapeutic
      target. In order to study expression patterns of topoisomerase IIIa we have
      produced a novel monoclonal antibody to human topoisomerase IIIa (TOPO3a-1A4),
      and used it to assess topoisomerase IIIa expression in a wide range of normal and
      neoplastic tissues. We have found that topoisomerase IIIa is expressed in a wide
      range of tissue types, with especially high concentrations in endothelial cells
      and stromal fibroblasts. No general relationship was observed between expression
      of topoisomerase IIIa and proliferation. Expression in neoplastic tissues often
      paralleled their normal counterparts, although certain tumours showed either
      increased (e.g. colonic adenoma) or reduced (e.g. gastric carcinoma, small cell
      carcinoma of bronchus) expression. If topoisomerase IIIa is found to be a target
      for chemotherapeutic agents, clinical response in different tumour types may be
      related to topoisomerase IIIa expression, which may be assessed using TOPO3a-1A4.

PMID- 10945500
TI  - Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to
      low-dose irradiation.
AB  - Low-dose hyper-radiosensitivity (HRS) (below 0.5 Gy) has been extensively
      documented in the past few years. The molecular basis of this phenomenon remains
      largely unknown and the purpose of this study was to investigate the possible
      implication of the DNA repair DNA-PK complex. The activity of the DNA-PK complex,
      i.e. Ku DNA-end binding activity and kinase activity of the whole complex, was
      studied in 10 human cancer cell lines, 2 h after 0.2, 0.5 and 1 Gy irradiation.
      After low-dose irradiation (0.2 Gy), a marked decrease in DNA-PK activity was
      found in all six cell lines exhibiting HRS, whereas the DNA-PK activity was
      increased in the four cell lines which did not exhibit HRS. This modulation of
      DNA-PK activity was a rapid phenomenon occurring within the 2 h following low
      dose radiation exposure. These data strongly suggest the implication of the DNA
      PK repair complex in the HRS phenomenon.

PMID- 10945499
TI  - Cytokine-mediated protection of human dendritic cells from prostate cancer
      induced apoptosis is regulated by the Bcl-2 family of proteins.
AB  - Prostate cancer is the most common cancer in men in the United States, and second
      in cancer-induced mortality. It is likely that tumour-induced immunosuppression
      is one of the reasons for low treatment efficacy in patients with advanced
      prostate cancer. It has been recently demonstrated that prostate cancer tissue is
      almost devoid of dendritic cells (DC), the major antigen-presenting cells
      responsible for the induction of specific antitumour immune responses. In this
      study, we have tested the hypothesis that prostate cancer induces progressive
      suppression of the DC system. We found that co-incubation of human DC with three
      prostate cancer cell lines led to the high levels of premature apoptosis of DC,
      which were significantly higher than in DC cultures co-incubated with normal
      prostate cells or blood leucocytes. Stimulation of DC for 24 hours with CD40
      ligand (CD154), IL-12 or IL-15 prior to their co-incubation with prostate cancer
      cells resulted in a significant increase in DC survival in the tumour
      microenvironment. Furthermore, activation of DC with these cytokines was also
      accompanied by increased expression of the anti-apoptotic protein Bcl-x(L) in DC,
      suggesting a possible mechanism involved in DC protection from apoptotic death.
      In summary, our data demonstrate that prostate cancer induces active elimination
      of DC in the tumour microenvironment. Stimulation of DC by CD154, IL-12 or IL-15
      leads to an increased expression of the anti-apoptotic protein Bcl-x(L) and
      increased resistance of DC to prostate cancer-induced apoptosis. These results
      suggest a new mechanism of tumour escape from immune recognition and demonstrate
      the cytokine-based approaches which might significantly increase the efficacy of
      DC-based therapies for cancer.

PMID- 10945501
TI  - Down-regulation of TGF-beta1 production restores immunogenicity in prostate
      cancer cells.
AB  - The objective of this study is to determine if a non-immunogenic Dunning's rat
      prostate cancer cell line, MATLyLu, can become immunogenic by reducing the
      endogenous production of TGF-beta1. An expression construct containing a DNA
      sequence in an antisense orientation to TGF-beta1 (TGF-beta1 antisense) was
      stably transfected into MATLyLu cells. Following transfection, cellular content
      of TGF-beta1 reduced from 70 to 10 pg per 2x10(4) cells and the rate of in vitro
      3H-thymidine incorporation increased 3-5-fold. After subcutaneous injection of
      tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence
      was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the
      control construct, but only 43% (9/21, P< or =0.05) for cells transfected with
      TGF-beta1 antisense. However, when cells were injected into immunodeficient hosts
      (athymic nude rats), the incidence of tumour development was 100% (10/10) for
      both the wild type MATLyLu cells and cells transfected with the control construct
      and 90% (9/10) for cells transfected with TGF-beta1 antisense. These observations
      support the concept that MATLyLu cells are immunogenic, when the endogenous
      production of TGF-beta1 is down-regulated.

PMID- 10945502
TI  - Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats.
AB  - Tissue protein hypercatabolism (TPH) is an important feature in cancer cachexia,
      particularly with regard to the skeletal muscle. The Yoshida AH-130 rat ascites
      hepatoma is a model system for studying the mechanisms involved in the processes
      that lead to tissue depletion, since it induces in the host a rapid and
      progressive muscle wasting, primarily due to TPH. The present study was aimed at
      investigating if IL-15, which is known to favour muscle fibre hypertrophy, could
      antagonize the enhanced muscle protein breakdown in this cancer cachexia model.
      Indeed, IL-15 treatment partly inhibited skeletal muscle wasting in AH-130
      bearing rats by decreasing (8-fold) protein degradative rates (as measured by 14C
      bicarbonate pre-loading of muscle proteins) to values even lower than those
      observed in non-tumour-bearing animals. These alterations in protein breakdown
      rates were associated with an inhibition of the ATP-ubiquitin-dependent
      proteolytic pathway (35% and 41% for 2.4 and 1.2 kb ubiquitin mRNA, and 57% for
      the C8 proteasome subunit, respectively). The cytokine did not modify the plasma
      levels of corticosterone and insulin in the tumour hosts. The present data give
      new insights into the mechanisms by which IL-15 exerts its preventive effect on
      muscle protein wasting and seem to warrant the implementation of experimental
      protocols involving the use of the cytokine in the treatment of pathological
      states characterized by TPH, particularly in skeletal muscle, such as in the
      present model of cancer cachexia.

PMID- 10945503
TI  - Interferon-alpha2b reduces phosphorylation and activity of MEK and ERK through a
      Ras/Raf-independent mechanism.
AB  - Interferon (IFN)-alpha affects the growth, differentiation and function of
      various cell types by transducing regulatory signals through the Janus tyrosine
      kinase/signal transducers of activation and transcription (Jak/STAT) pathway. The
      signalling pathways employing the mitogen-activated ERK-activating kinase (MEK)
      and the extracellular-regulated kinase (ERK) are critical in growth factors
      signalling. Engagement of the receptors, and subsequent stimulation of Ras and
      Raf, initiates a phosphorylative cascade leading to activation of several
      proteins among which MEK and ERK play a central role in routing signals critical
      in controlling cell development, activation and proliferation. We demonstrate
      here that 24-48 h following treatment of transformed T- and monocytoid cell lines
      with recombinant human IFN-alpha2b both the phosphorylation and activity of MEK1
      and its substrates ERK1/2 were reduced. In contrast, the activities of the
      upstream molecules Ras and Raf-1 were not affected. No effect on MEK/ERK activity
      was observed upon short-term exposure (1-30 min) to IFN. The anti-proliferative
      effect of IFN-alpha was increased by the addition in the culture medium of a
      specific inhibitor of MEK, namely PD98059. In conclusion, our results indicate
      that IFN-alpha regulates the activity of the MEK/ERK pathway and consequently
      modulates cellular proliferation through a Ras/Raf-independent mechanism.
      Targeting the MEK/ERK pathway may strengthen the IFN-mediated anti-cancer effect.

PMID- 10945504
TI  - Porphyrin biosynthesis in human Barrett's oesophagus and adenocarcinoma after
      ingestion of 5-aminolaevulinic acid.
AB  - 5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis, which is used for
      ALA-based photodynamic therapy (ALA-PDT), was studied in tissues of 10 patients
      with Barrett's oesophagus (BE) and adenocarcinoma of the oesophagus (AC)
      undergoing oesophagectomy at a mean time interval of 6.7 h after the ingestion of
      ALA (60 mg kg(-1)). In BE, AC, squamous epithelium (SQ) and gastric cardia, the
      activities of the haem biosynthetic enzymes porphobilinogen deaminase (PBG-D) and
      ferrochelatase (FC) and the PDT power index--the ratio between PBG-D and FC in BE
      and AC in comparison with SQ--were determined before ALA ingestion. Following ALA
      administration, ALA, porphobilinogen, uroporphyrin I and PPIX were determined in
      tissues and plasma. The PDT power index did not predict the level of
      intracellular accumulation of PPIX found at 6.7 h. In BE, there was no
      selectivity of PPIX accumulation compared to SQ, whereas in half of patients with
      AC selectivity was found. Higher haem biosynthetic enzyme activities (i.e. PBG-D)
      and lower PPIX precursor concentrations were found in BE and AC compared to SQ.
      It is therefore possible that PPIX levels will peak at earlier time intervals in
      BE and AC compared to SQ.

PMID- 10945505
TI  - Proteolysis of microtubule associated protein 2 and sensitivity of pancreatic
      tumours to docetaxel.
AB  - We have studied the state of microtubule associated protein 2 (MAP2) in the
      pancreatic ductal adenocarcinomas P03 and P02 (sensitive and refractory to
      docetaxel respectively) since they express the corresponding mRNA and MAP2
      related peptides. Immunohistochemical localization showed that in tumour P03 the
      MAP2-related peptides are highly expressed and confined to the epithelial
      malignant cells while in P02 the Intensity of the immunostaining is lower.
      However, anti alpha-tubulin staining followed a similar pattern suggesting that
      the net amount of macromolecular structures in the sensitive tumour is higher
      than in the refractory one. This may explain its higher sensitivity to docetaxel,
      because tubulin assembled into microtubules is the target of the drug. We found
      that protein extracts from both tumours differed in their proteolytic activity on
      rat brain MAP2. Since the proteolysis pattern obtained was similar to the one
      produced by Cathepsin D, we studied the effect of MAP2 proteolysed by this enzyme
      on microtubule formation in vitro. Proteolysis was found to increase the tendency
      of tubulin to assemble into macromolecular structures (microtubules and
      aggregates) in the presence of docetaxel. This suggests that in vivo proteolysis
      of MAP2 might increase microtubule alterations and potentiate the antitumour
      effect of docetaxel.

PMID- 10945507
TI  - The safety profile of the fluoroquinolones.
AB  - BACKGROUND: Premarketing trials showed the fluoroquinolone agents to have a
      favorable side-effect profile, with treatment-related adverse events comprising
      gastrointestinal, central nervous system, and dermatologic effects that were
      generally mild and reversible on cessation of treatment. However, postmarketing
      surveillance studies have identified severe adverse events, including severe
      anaphylaxis, QTc-interval prolongation, and potential cardiotoxicity, associated
      with 3 quinolone agents that either resulted in the removal of the agent from the
      market (temafloxacin and grepafloxacin) or significantly restricted its use due
      to substantial mortality and morbidity associated with liver toxicity
      (trovafloxacin). To date, there have been no such significant adverse events
      associated with the older fluoroquinolone agents, including ciprofloxacin,
      ofloxacin, norfloxacin, and levofloxacin. However, there are fewer data from
      postmarketing surveillance studies on the most recently approved agents, such as
      moxifloxacin and gatifloxacin, or agents awaiting approval, such as gemifloxacin.
      OBJECTIVE: This paper examines safety data from the premarketing trials and
      postmarketing surveillance studies of fluoroquinolones available in the United
      States. METHODS: A MEDLINE search was performed to identify all English-language
      studies published since 1980 concerning the safety profiles of the
      fluoroquinolones. CONCLUSIONS: The fluoroquinolone antibacterial agents offer
      broad-spectrum therapy in patients with a variety of infections. Given similar
      spectra of activity, the choice between quinolones may be based on differences in
      efficacy and safety or tolerability profiles. Most drug reactions involving these
      agents are minor and reversible on discontinuing treatment, but adverse effects
      can be associated with significant mortality and morbidity, as was seen in the
      case of trovafloxacin and temafloxacin.

PMID- 10945506
TI  - Oestrogen inactivation in the colon: analysis of the expression and regulation of
      17beta-hydroxysteroid dehydrogenase isozymes in normal colon and colonic cancer.
AB  - Epidemiological data suggest that oestrogen contributes to the aetiology of
      colonic cancer. Furthermore, recent studies have suggested that local hormone
      metabolism may play a key role in determining colonic responsiveness to
      oestrogen. To further clarify this mechanism we have characterized the expression
      and regulation of isozymes of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in
      vitro and in situ. Immunohistochemistry was used to confirm expression of the
      type 2 and 4 isozymes of 17beta-HSD (17beta-HSD2 and 4) in normal colonic
      epithelial cells. Parallel studies suggested that both isozymes were abnormally
      expressed in colonic tumours and this was confirmed by Western blot analyses.
      Abnormal expression of 17beta-HSD2 and 4 proteins was also observed in Caco-2, HT
      29 and SW620 colonic cancer cell lines, although the overall pattern of oestrogen
      metabolism in these cells was similar to that seen in primary colonic mucosal
      tissue. The predominant activity (conversion of oestradiol to oestrone) was
      highest in Caco-2>SW620>HT-29, which correlated inversely with the rate of
      proliferation of the cell lines. Regulatory studies using SW620 cells indicated
      that the most potent stimulator of oestradiol to oestrone inactivation was the
      antiproliferative agent 1,25-dihydroxyvitamin D3 (1,25D3), whilst oestradiol
      itself inhibited 17beta-HSD activity. Both oestradiol and 1,25D3 decreased mRNA
      for 17beta-HSD2 and 4. Data indicate that the high capacity for inactivation of
      oestrogens in the colon is associated with the presence of 17beta-HSD2 and 4 in
      epithelial cells. Abnormal expression of both isozymes in colonic cancer cells
      and the stimulation of oestrogen inactivation by the antiproliferative agent
      1,25D3 highlights a possible role for 17beta-HSD isozymes as modulators of
      colonic cell proliferation.

PMID- 10945508
TI  - Cefdinir versus cefaclor in the treatment of uncomplicated urinary tract
      infection.
AB  - OBJECTIVE: This multicenter, double-blind, randomized, parallel-group study was
      conducted in Europe, South Africa, and Australia to compare the clinical and
      microbiologic efficacy and the tolerability of a cephalosporin antibiotic,
      cefdinir, with those of cefaclor in the treatment of uncomplicated urinary tract
      infection. METHODS: Patients were randomized in a 1:1 ratio to 5 days of
      treatment with either cefdinir 100 mg BID or cefaclor 250 mg TID. RESULTS: A
      total of 661 patients were randomized to treatment. They were 90% female, with a
      median age of 44 years. There were no clinically important differences between
      groups in terms of demographic characteristics or symptoms on admission. The most
      frequently isolated pathogens in admission urine cultures were Escherichia coli
      (383 patients), Proteus mirabilis (20 patients), Staphylococcus saprophyticus (14
      patients), and Klebsiella pneumoniae (9 patients). Of the admission pathogens
      with documented susceptibility results, significantly more were resistant to
      cefaclor (6.7%) than to cefdinir (3.7%; P < 0.003). Significantly more admission
      isolates of E. coli were resistant to cefaclor (5.1%) than to cefdinir (2.0%; P <
      0.007). A total of 383 patients were assessable for efficacy, 196 in the cefdinir
      group and 187 in the cefaclor group. Clinical cure rates and microbiologic
      response rates for cefdinir and cefaclor were statistically equivalent at 5 to 9
      days posttherapy (test-of-cure visit), using a 95% CI approach. The rate of
      treatment-related adverse events was higher in cefdinir-treated patients (20.2%)
      than in cefaclor-treated patients (13.0%; P = 0.025), mainly due to the greater
      frequency of diarrhea in the former group. However, only 4 patients (1.2%)
      discontinued cefdinir treatment due to diarrhea. CONCLUSION: Empiric therapy with
      cefdinir appears to be a reasonable choice for patients with uncomplicated
      urinary tract infection in whom cephalosporin treatment is indicated.

PMID- 10945509
TI  - A comparison of the relative efficacy and clinical performance of olopatadine
      hydrochloride 0.1% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic
      solution in the conjunctival antigen challenge model.
AB  - OBJECTIVE: The purpose of this study was to compare the relative efficacy and
      clinical performance of olopatadine hydrochloride 0.1% ophthalmic solution and
      ketotifen fumarate 0.025% ophthalmic solution in the conjunctival antigen
      challenge model. METHODS: This was a prospective, randomized, double-masked,
      contralaterally controlled, single-center, antigen challenge study. Of the 53
      subjects screened, 32 were enrolled and completed the study. The study comprised
      3 visits. Primary efficacy variables were ocular itching (assessed at visits 2
      and 3) and subject satisfaction (assessed at visit 3). Tolerability variables
      were slit-lamp findings (all visits), visual acuity (all visits), ocular comfort
      after drug instillation (visit 3), and adverse events (visits 2 and 3). At visit
      1, the antigen concentration that elicited a positive ocular allergic response
      was determined, and this concentration was confirmed at visit 2. Subjects graded
      itching on a 5-point scale at 3, 5, and 10 minutes postchallenge. The scores from
      this visit were used as baseline scores and compared with scores from visit 3 to
      determine drug efficacy. At visit 3, subjects were randomly assigned to 2
      treatment groups. Group A received 1 drop of olopatadine in the right eye and I
      drop of ketotifen in the left eye. Group B received 1 drop of olopatadine in the
      left eye and 1 drop of ketotifen in the right eye. Following drug instillation,
      the subjects assessed the comfort level in each eye. Twelve hours after
      instillation, subjects were challenged with the antigen concentration that
      elicited a positive response at the previous visits. Itching was subjectively
      graded at 3, 5, and 10 minutes postchallenge. Subjects were asked to choose which
      therapy they were more satisfied with. RESULTS: Twelve hours after
      administration, efficacy scores for olopatadine were significantly higher than
      those for ketotifen at 3 and 5 minutes postchallenge (1.84 and 1.75 vs 1.25 and
      1.34; P < 0.05). Olopatadine-treated eyes were rated significantly more
      comfortable than those treated with ketotifen immediately after drug instillation
      (1.25 vs 2.09; P < 0.05) and 12 hours later, as measured by patient ratings of
      ocular comfort. Of the 22 subjects who had a preference, 16 (73%) were more
      satisfied with olopatadine than with ketotifen. CONCLUSIONS: Olopatadine is more
      effective than ketotifen in reducing the itching associated with allergic
      conjunctivitis in the antigen challenge model. Olopatadine caused less ocular
      discomfort than ketotifen and was preferred by approximately 3 times as many
      patients as was ketotifen.

PMID- 10945510
TI  - Efficacy of naftidrofuryl in patients with vascular or mixed dementia: results of
      a multicenter, double-blind trial.
AB  - BACKGROUND: Dementia is a cerebral disorder resulting in a progressive
      deterioration of intellectual function that compromises the patient's ability to
      function. The diagnostic criteria for dementia are primarily clinical and are
      based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition. The Hachinski score and computed tomography of the brain help
      distinguish between degenerative and vascular dementias. OBJECTIVE: This study
      examined the efficacy of naftidrofuryl in patients with vascular or mixed
      dementia. METHODS: This multicenter, randomized, double-blind study compared
      naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed
      dementia. A preliminary 2-month washout period allowed selection of patients who
      were compliant with treatment. The end point was change in the scores on the
      Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State
      Examination. RESULTS: Eighty-four patients were assessable on an intent-to-treat
      basis, and 74 were assessable for the per-protocol analysis (on-treatment).
      Statistically significant improvements in cognitive and global function were
      observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated,
      and produced no clinically significant abnormalities in laboratory test results.
      CONCLUSION: The results of this study suggest that naftidrofuryl is effective and
      well tolerated in treating the symptoms of vascular and mixed dementia.

PMID- 10945511
TI  - An estradiol matrix transdermal system for the prevention of postmenopausal bone
      loss.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and
      tolerability of 2 years' application of an estradiol matrix transdermal system
      for the prevention of postmenopausal bone loss. METHODS: In this multicenter,
      randomized, placebo-controlled, parallel-group study, 261 surgically or naturally
      postmenopausal women were randomized to apply the estradiol matrix transdermal
      system (0.025, 0.0375, 0.05, or 0.1 mg/d) or matching placebo twice a week for 2
      years. The study was double blind with respect to treatment (active vs placebo)
      but not to the dose levels of active treatment (because of the differing sizes
      and shapes of the patches). In addition to receiving the assigned treatment, the
      100 nonhysterectomized women received 2.5 mg medroxyprogesterone acetate daily
      throughout the study. RESULTS: The evaluable group (n = 259) had a mean age of 52
      years and a mean duration of menopause of 32 months. Following 2 years of
      treatment, there were significant differences in favor of estradiol between all
      doses of the estradiol matrix transdermal system and placebo in terms of the
      percentage change from baseline in the bone mineral density (BMD) of the L1-L4
      anteroposterior lumbar spine (0.1 and 0.05 mg/d, P < 0.001; 0.0375 mg/d, P =
      0.024; 0.025 mg/d, P = 0.002). Percentage changes from baseline in the BMD of the
      femoral neck after 2 years of treatment also consistently demonstrated the
      efficacy of the estradiol matrix transdermal system compared with placebo (all, P
      < or = 0.044). The estradiol matrix transdermal system was well tolerated.
      CONCLUSION: The estradiol matrix transdermal system was effective in preventing
      postmenopausal bone loss at dosages of 0.025 to 0.1 mg/d, and had a safety
      profile consistent with the known effects of estrogen/progestin.

PMID- 10945512
TI  - Stages of change for adherence with medication regimens for chronic disease:
      development and validation of a measure.
AB  - BACKGROUND: The stages-of-change (SOC) model has been used to explain and predict
      how behavior change occurs, but it is new as an approach to understanding why
      patients fail to take their medications as prescribed. OBJECTIVE: This study
      validated a 2-item measure of SOC for adherence with medication regimens in 2
      groups of patients prescribed pharmacologic therapy for chronic conditions.
      METHODS: Two cross-sectional studies of attitudes toward medication adherence
      included the same measure of SOC for medication adherence. One was a sample of
      161 HIV-positive patients in the United States, and the other was an
      international sample of 731 patients with hypertension. The validity of the
      measure of SOC for medication adherence was examined in both convenience samples
      using previously validated self-reported measures of adherence (the Medication
      Adherence Scale and a measure of adherence from the Medical Outcomes Study), and
      in the HIV sample using electronic monitoring of adherence behavior in 85
      patients. RESULTS: Construct validity was demonstrated in both samples by
      associations between SOC and the previously validated measures of adherence (P <
      0.001), and predictive validity was supported by significant associations between
      SOC for medication adherence and electronically monitored medication-taking
      behavior during the next 30 days (P < 0.03). CONCLUSIONS: Behavior-change theory
      suggests that stage-tailored communication strategies are more effective than
      uniform health-promotion messages. Our results provide a foundation for the
      development of interventions for medication adherence that are tailored to
      patients' readiness for change. Our validated 2-item measure of SOC for
      medication adherence can be used to match communication strategies to individual
      motivation and readiness for adherence with chronic disease medication regimens.

PMID- 10945513
TI  - Effect of macrolides as part of initial empiric therapy on medical outcomes for
      hospitalized patients with community-acquired pneumonia.
AB  - OBJECTIVE: The goal of this study was to compare the outcomes of hospitalized
      patients receiving a nonpseudomonal third-generation cephalosporin with or
      without a macrolide for the treatment of community-acquired pneumonia (CAP).
      BACKGROUND: The initial treatment of CAP is usually based on empirically selected
      antibiotic therapy. The need for coverage of atypical pathogens in hospitalized
      patients is widely debated, and regional variations may exist. METHODS: All
      patients admitted to a community hospital or to a university hospital for 1 year
      who were aged > or =18 years and had a principal discharge diagnosis of pneumonia
      with no organism specified according to the International Classification of
      Diseases, Ninth Revision, Clinical Modification were evaluated. Each patient's
      medical chart was reviewed by a clinical pharmacist at each facility. The
      following information was collected for each patient using a standardized form:
      demographic characteristics, coexisting illnesses, length of hospital and
      intensive care unit stays, antibiotic regimens, length of parenteral and oral
      therapy, laboratory and radiographic findings (ie, blood urea nitrogen, glucose,
      hematocrit, sodium, PO2, pH, and pleural effusion), physical examination results,
      and mortality. Patients treated with a nonpseudomonal third-generation
      cephalosporin with or without a macrolide were included in this analysis.
      Categoric variables were compared using the chi-square test or the Fisher exact
      test, and continuous variables were compared using the Mann-Whitney U test. A P
      value < 0.05 was considered statistically significant. RESULTS: A total of 213
      patients met the entry criteria and were treated with a nonpseudomonal third
      generation cephalosporin with (116 patients) or without (97 patients) a
      macrolide. The mean (+/- SD) age of the patients was 62.2+/-19.6 years; 47% were
      male. The most common comorbid conditions were chronic obstructive pulmonary
      disease, diabetes mellitus, congestive heart failure, and cerebrovascular
      accident (CVA). Of the 116 patients who received a macrolide, the majority (66%)
      received erythromycin. Other macrolides used were clarithromycin (19%) and oral
      azithromycin (15%). There were no statistical differences between patients who
      did and did not receive a macrolide in terms of comorbid illnesses, length of
      hospital stay (5.2+/-2.8 vs 5.2+/-3.4 days, respectively), length of intravenous
      antibiotic therapy (4.4+/-2.5 vs 4.1+/-2.3 days, respectively), or mortality
      (0.9% vs 3.1%, respectively; P = 0.333). The only difference between the groups
      was in age. Those patients who received a macrolide were significantly younger
      than those who received only a nonpseudomonal third-generation cephalosporin
      (57.4+/-19.2 years vs 67.9+/-18.5 years; P < 0.001). However, when age and
      severity of illness were taken into account, no difference existed between the
      patients who received a nonpseudomonal third-generation cephalosporin alone or in
      combination with a macrolide. CONCLUSIONS: We concluded that the addition of a
      macrolide to a nonpseudomonal third-generation cephalosporin as initial therapy
      for the treatment of CAP may not be necessary. A randomized, prospective clinical
      trial comparing a nonpseudomonal third-generation cephalosporin alone and in
      combination with a macrolide is warranted.

PMID- 10945515
TI  - Adverse effects of benzalkonium chloride on the nasal mucosa: allergic rhinitis
      and rhinitis medicamentosa.

PMID- 10945516
TI  - Highlights 2000 Lecture. The Internet: the road to smart nuclear medicine.

PMID- 10945514
TI  - Combination hydrocodone and ibuprofen versus combination codeine and
      acetaminophen for the treatment of chronic pain.
AB  - OBJECTIVE: The objective of this study was to compare the effectiveness of
      combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination
      codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain.
      BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed
      dose combination analgesic containing an opioid and ibuprofen. METHODS: In this
      randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4
      week, multicenter study, 469 patients were randomly assigned to receive a 1
      tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and
      ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination
      codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator,
      every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief
      scores, number of daily doses of study medication, number of daily doses of
      supplemental analgesics, number of patients who discontinued therapy due to an
      unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the
      469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was
      51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145;
      30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic
      (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and
      other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the
      study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid
      combination analgesics. The overall mean daily pain relief score was
      significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group
      (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall
      mean number of daily doses of study medication was significantly less in the HI2
      group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA
      group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of
      supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49)
      than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P =
      0.010). The number of patients who discontinued treatment due to an
      unsatisfactory analgesic response was significantly less in the HI2 group (2;
      1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than
      HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and
      CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001
      vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P =
      0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1
      and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001
      vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs
      HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and
      CA in any efficacy variable. There were no significant differences in the number
      of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%),
      and CA (129; 80.6%) groups. However, the mean number of patients who discontinued
      treatment due to adverse events was significantly greater in the HI2 group (40;
      26.1%) than in the HI1 group (23; 14.7%) (P = 0.013). CONCLUSIONS: The results of
      this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and
      ibuprofen 200 mg may be more effective than either 1-tablet doses of this
      combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300
      mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200
      mg may be as effective as 2-tablet doses of combination codeine 30 mg and
      acetaminophen 300 mg.

PMID- 10945517
TI  - Henry N. Wagner, Jr, Lecture. Clinical PET: role in diagnosis and management.

PMID- 10945518
TI  - 123I-IPPA SPECT for the prediction of enhanced left ventricular function after
      coronary bypass graft surgery. Multicenter IPPA Viability Trial Investigators.
      123I-iodophenylpentadecanoic acid.
AB  - Fatty acids are the prime metabolic substrate for myocardial energy production.
      Hence, fatty acid imaging may be useful in the assessment of myocardial
      hibernation. The goal of this prospective, multicenter trial was to assess the
      use of a fatty acid, 123I-iodophenylpentadecanoic acid (IPPA), to identify
      viable, hibernating myocardium. METHODS: Patients (n = 119) with abnormal left
      ventricular wall motion and a left ventricular ejection fraction (LVEF) < 40% who
      were already scheduled to undergo coronary artery bypass grafting (CABG)
      underwent IPPA tomography (rest and 30-min redistribution) and blood-pool
      radionuclide angiography within 3 d of the scheduled operation. Radionuclide
      angiography was repeated 6-8 wk after CABG. The study endpoint was a > or =10%
      increase in LVEF after CABG. The number of IPPA-viable abnormally contracting
      segments necessary to predict a positive LVEF outcome was determined by receiver
      operating characteristic (ROC) curves and was included in a logistic regression
      analysis, together with selected clinical variables. RESULTS: Before CABG,
      abnormal IPPA tomography findings were seen in 113 of 119 patients (95%), of whom
      71 (60%) had redistribution in the 30-min images. The LVEF increased modestly
      after CABG (from 32% +/- 12% to 36% +/- 8%, P< 0.001).A > or =10% increase in
      LVEF after CABG occurred in 27 of 119 patients (23%). By ROC curves, the best
      predictor of a > or =10% increase in LVEF was the presence of > or =7 IPPA-viable
      segments (accuracy, 72%; confidence interval, 64%-80%). Among clinical and
      scintigraphic variables, the single most important predictor also was the number
      of IPPA-viable segments (P = 0.008). The number of IPPA-viable segments added
      significant incremental value to the best clinical predictor model. CONCLUSION:
      Asubstantial increase in LVEF occurs after CABG in only a minority of patients
      (23%) with depressed preoperative function. The number of IPPA-viable segments is
      useful in predicting a clinically meaningful increase in LVEF.

PMID- 10945519
TI  - Echocardiographic validation of gated SPECT ventricular function measurements.
AB  - Left ventricular (LV) volumes are valuable prognostic indicators in the
      management of coronary artery disease and traditionally have been obtained by x
      ray contrast angiography or echocardiography. There now are several scintigraphic
      methods to compute volumes that are based on different LV modeling assumptions.
      Both the reasons that calculations from different nuclear techniques can disagree
      with one another and the relationship of these values to the more conventional
      echocardiographic measurements must be investigated thoroughly for calculations
      to be interpretable for individual patients. METHODS: Echocardiographic volumes
      were determined in 33 retrospective subjects with coronary artery disease (mean
      age, 61 +/- 12 y; 42% men; 70% with abnormal perfusion and 58% with abnormal
      segmental wall motion) using the modified Simpson's rule technique applied to
      digitized apical 4-chamber and apical 2-chamber views of 4 averaged heartbeats.
      These volumes were compared with those from 3 gated SPECT methods based on
      Simpson's rule LV modeling similar to standard echocardiographic algorithms
      (SPECT EF from St. Luke's-Roosevelt Hospital) (method 1), Gaussian myocardial
      count profile curve fitting (QGS from Cedars-Sinai Medical Center) (method 2),
      and an endocardial model based on perfusion sampling and count-based thickening
      (Cardiac Toolbox from Emory University) (method 3). RESULTS: By ANOVA, there were
      no significant differences among ejection fractions (EFs), but there were for
      volumes. Paired t test analysis showed volumes from methods 2 and 3 to be
      significantly larger than echocardiographic volumes and larger than those of
      method 1. Linear regression analysis comparing gated SPECT and echocardiographic
      volumes showed a nearly identical strong correlation (r = 0.92; P < 0.000001) for
      all 3 methods. Excellent correlation also was found among gated SPECT volumes
      from the 3 methods (r = 0.94). Bland-Altman analysis and t tests showed that
      method 1 volumes (70 +/- 61 mL) were the same as for echocardiography (77 +/- 55
      mL), but volumes were overestimated by method 2 (105 +/- 74 mL) and method 3 (127
      +/- 92 mL), particularly for larger volumes. Pearson coefficients for EFs
      compared with echocardiography were r = 0.82, 0.75, and 0.72 for methods 1-3,
      respectively. EFs correlated strongly among the 3 gated SPECT methods (r = 0.86
      0.92). The Fisher z test showed no differences among these methods for any of the
      volume or EF linear correlation analyses. CONCLUSION: All gated SPECT parameters
      correlated well with echocardiographic values. However, the gated SPECT method
      for which underlying assumptions most closely resembled those commonly used in
      echocardiography produced mean volume values closest in agreement with
      echocardiographic measurements.

PMID- 10945520
TI  - Minimizing liver, bowel, and gastric activity in myocardial perfusion SPECT.
AB  - When using 99mTc-tetrofosmin for myocardial perfusion SPECT, increased liver,
      intestinal, or gastric activity may create a major problem in the visual and
      quantitative interpretation Of the inferoposteroseptal walls, particularly at
      rest. The aim of this study was to determine what measures were required to
      minimize this extracardial activity. METHODS: Ninety-seven patients had a SPECT
      scan at rest without attenuation correction. They were divided into 3 groups.
      Preparation consisted of no action taken (group 1), 150 mL whole milk 10 min
      after administration of tetrofosmin (group 2), or 450 mL water 10 min before
      acquisition (group 3). A further 55 patients had a SPECT scan at rest with
      attenuation correction. They were also divided into 3 groups, and preparation
      consisted of 150 mL whole milk 10 min after administration of tetrofosmin (group
      4), 450 mL water 10 min before acquisition (group 5), or both whole milk and
      water (group 6). The presence of activity in liver, bowel, and stomach was
      determined visually on reconstructed images. Activity was defined as interfering
      when it might result in either an underestimation or an overestimation of the
      uptake in the myocardial wall. RESULTS: Interfering activity was seen in 83% of
      the patients in group 1, in 74% in group 2, in 33% in group 3, in 61% in group 4,
      in 67% in group 5, and in 20% of group 6. CONCLUSION: The interpretation of
      inferoposteroseptal wall activity on myocardial rest SPECT images is facilitated
      by having the patient drink both whole milk and water at specified times before
      data acquisition.

PMID- 10945521
TI  - Estimation of myocardial perfusion and viability using simultaneous 99mTc
      tetrofosmin--FDG collimated SPECT.
AB  - This study was designed to elucidate the usefulness of crosstalk correction for
      dual-isotope simultaneous acquisition (DISA) with 99mTc-tetrofosmin and FDG in
      estimating myocardial perfusion and viability. METHODS: Eighteen patients with
      coronary artery disease were studied. First, SPECT was performed with a low
      energy high-resolution collimator after a single injection of 99mTc-tetrofosmin
      (single 99mTc-tetrofosmin). Second, PET and DISA with an ultra-high-energy
      collimator were performed after glucose loading and an injection of FDG. DISA was
      designed to operate with simultaneous 3-channel acquisition, and weighted scatter
      correction of crosstalk from the 18F photopeak to the 99mTc photopeak was
      performed by modification of an existing dual-window technique. The FDG SPECT
      images were compared with the images obtained by PET. Both crosstalk-corrected
      and uncorrected 99mTc-tetrofosmin images were generated and compared with the
      single 99mTc-tetrofosmin images. RESULTS: Regional percentage uptake of FDG
      agreed well between DISA and PET. However, regional percentage uptake of 99mTc
      tetrofosmin was generally higher on the uncorrected 99mTc-tetrofosmin images than
      on the single 99mTc-tetrofosmin images, especially in areas of low flow
      (percentage count of 99mTc-tetrofosmin > or = 50%). The crosstalk correction
      contributed to improving the agreement between regional percentage uptakes and
      significantly improved the detectability of myocardial perfusion-metabolism
      mismatching. CONCLUSION: With 3-channel acquisition and weighted-scatter
      correction of crosstalk from the 18F photopeak to the 99mTc photopeak, DISA with
      99mTc-tetrofosmin and FDG is feasible for assessing regional myocardial perfusion
      and viability.

PMID- 10945522
TI  - Scintimammography with 11beta-methoxy-(17alpha,20Z)-[123I]iodovinylestrad iol: a
      complementary role to 99mTc-methoxyisobutyl isonitrile in the characterization of
      breast tumors.
AB  - The aim of this study was to investigate a possible relationship between 99mTc
      methoxyisobutyl isonitrile (MIBI) uptake and the estrogen receptor (ER) status of
      breast tumors as determined by 11beta-methoxy-(17alpha,20Z)
      [123I]iodovinylestradi ol (MIVE) scintimammography. METHODS: Thirteen patients
      referred for MIVE scintimammography after abnormal mammography or finding of a
      suspect mass on physical examination were injected intravenously with MIVE.
      Planar images of the breasts and axillary region were taken with both
      radiopharmaceuticals and compared with pathologic examination of the tumor tissue
      and in vitro ER quantification. RESULTS: The presence of cancerous tissue, as
      indicated by MIBI uptake, is a prerequisite for the accumulation of MIVE by the
      breast tumors. There was no statistically significant correlation between the
      MIBI and MIVE tumor uptake ratios. However, the latter correlate well with the
      presence of ER, as determined by an in vitro assay. CONCLUSION: MIVE scans add
      unique information concerning the tumor ER status in breast cancer patients,
      which could contribute to a better characterization of the tumor and aid in the
      selection of the most appropriate treatment protocol.

PMID- 10945523
TI  - Prediction of renal transplant survival from early postoperative radioisotope
      studies.
AB  - It has been routine at the University of Alabama Medical Center to obtain a
      radionuclide renal function study immediately after transplantation (usually
      within 3 d) that includes estimation of effective renal plasma flow (ERPF) from a
      single plasma sample in addition to imaging. We present here the correlation
      between baseline measurements and the 1-y graft survival. METHODS: Two cohort
      years were reviewed: 1988, when 131I-orthoiodohippurate (OIH) was used; and 1995,
      when 99mTc-mercaptoacetyltriglycine (MAG3) was used. ERPF was measured
      concurrently with gamma-camera imaging by previously published single-injection,
      single-sample methods (converting MAG3 clearance to ERPF by means of a correction
      factor). RESULTS: Graft survival during the first postoperative year improved
      significantly in the interval between cohort years, from 74% of 147 cadaver (CD)
      grafts in 1988 to 91% of 200 CD grafts in 1995 (log rank test, P < 0.05). In
      contrast, for living related donor (LRD) grafts there was no significant change,
      from 91% of 66 in 1988 to 91% of 83 in 1995. The baseline ERPF was a significant
      predictor of graft survival in both 1988 and 1995 (Wilcoxon test, P > 0.05). For
      LRD grafts the association was not significant in either year. Using MAG3 (1995),
      the peak time and the ratio of counting rate (R) at 20 min to that at 3 min
      (R20:3) were also significant predictors for CD graft survival. Using OIH (1988
      cohort), the correlation with peak time did not reach significance, and the R20:3
      measurement was not available. Although multivariate combinations (Cox
      proportional hazards model) did not have significantly more predictive value at
      the 95% confidence level than ERPF or R20:3 alone, some statisticians suggest a
      75% confidence level for adding an additional covariate to a multivariate model.
      Use of this level led to a model including both ERPF and R20:3. CONCLUSION:
      Single-sample ERPF measured in the immediate post-transplant period, whether from
      OIH clearance or MAG3 clearance, was a statistical predictor of graft survival
      for CD transplants. For MAG3, the peak time and R20:3 were also significant
      predictors. These associations held only for CD transplants and not for LRD
      transplants.

PMID- 10945524
TI  - Aspirin renography and captopril renography in the diagnosis of renal artery
      stenosis.
AB  - Preliminary data suggest that aspirin renography is more sensitive than captopril
      renography for indicating renal artery stenosis (RAS). Considering that aspirin,
      compared with captopril, reduces renal blood flow and, thus, tubular tracer
      delivery in poststenotic kidneys, aspirin renography is expected to be more
      useful, particularly if tubular tracers are used. METHODS: We prospectively
      compared aspirin renography (20 mg/kg orally) and captopril renography (25 mg
      orally) with 99mTc-mercaptoacetyltriglycine in 75 consecutive patients suspected
      of having RAS. RESULTS: RAS, diagnosed as stenosis of more than 50% on
      angiography, was found unilaterally in 34 patients and bilaterally in 17
      patients. RAS was absent in 24 patients. The sensitivities for unilateral RAS or
      bilateral RAS (i.e., stenosis that was at least unilateral) were, respectively,
      88% and 88% for captopril renography and 82% and 94% for aspirin renography (not
      significant). The overall specificity was 75% for captopril renography and 83%
      for aspirin renography (not significant). Tracer uptake ratios, time to peak
      activity, and percentage of 20-min tracer retention were also not significantly
      different for captopril and aspirin renography. Subgroup analysis of modest (50
      75%) and severe (> or =75%) RAS, or of plasma creatinine greater than 120
      micromol/L, also showed no difference between captopril and aspirin renography.
      CONCLUSION: We conclude that for identification of RAS, the usefulness of aspirin
      renography equals, but does not surpass, that of captopril renography.

PMID- 10945525
TI  - Test-retest reproducibility of extrastriatal dopamine D2 receptor imaging with
      [123I]epidepride SPECT in humans.
AB  - This study evaluated the test-retest reproducibility of D2 receptor
      quantification in the thalamus and temporal cortex using [123I]epidepride SPECT.
      METHODS: Ten healthy volunteers (4 men, 6 women; age range, 19-46 y) underwent 2
      SPECT studies (interval, 2-26 d) using a bolus-plus-constant-infusion paradigm
      (bolus-to-infusion ratio = 6 h; infusion time = 9 h). Plasma clearance (in liters
      per hour) and free fraction (f1) of the parent tracer were measured.
      Radioactivity (in becquerels per gram) in the thalamus, temporal cortex, and
      cerebellum were normalized to the infusion rate (in becquerels per hour).
      Normalized striatal radioactivity was also measured to assess reproducibility in
      regions with a high density of receptors and better counting statistics. The
      outcome measures obtained were V3 (receptor density [Bmax]/equilibrium
      dissociation constant [KD]), V3' (f1 x Bmax/KD), and RT (specific-to
      nondisplaceable tissue ratio). RESULTS: Test-retest variability and reliability
      (intraclass correlation coefficient) were 10.8% and 0.88, respectively, for
      plasma clearance and 15.3% and 0.77, respectively, for f1. The test-retest
      variability of brain-specific (target minus nondisplaceable) radioactivity was
      higher in the thalamus and temporal cortex than in the striatum, although
      reliability was comparable. Among the outcome measures, V3' showed better test
      retest variability and reliability in the thalamus (13.3% and 0.75, respectively)
      and temporal cortex (13.4% and 0.86, respectively). CONCLUSION: Brain
      radioactivity was the main source of variability for quantification of
      extrastriatal D2 receptors with [123I]epidepride. The reproducibility of outcome
      measures in extrastriatal regions was good. However, because receptor density was
      lower in extrastriatal regions than in the striatum, the counting statistics in
      these regions were low and reproducibility was affected by the higher test-retest
      variability of brain-specific radioactivity. Compared with V3 and V3', RT showed
      less test-retest variability in the thalamus and temporal cortex but lower
      reliability. Moreover, measurement of RT may be affected by the presence of
      potential lipophilic metabolites entering the brain.

PMID- 10945526
TI  - PET studies of the effects of aerobic exercise on human striatal dopamine
      release.
AB  - In vivo microdialysis studies have shown that exercise increases the
      concentration of dopamine (DA) in the striatum of the rat brain. It has also been
      shown that PET with [11C]raclopride can be used to assess changes in brain DA
      induced by drugs and by performance tasks such as playing a video game. The
      purpose of this study was to evaluate the effects of exercise (treadmill running)
      on striatal DA release in the human brain. METHODS: Twelve healthy volunteers (5
      women, 7 men; mean age, 32 +/- 5 y; age range, 25-40 y) with a history of regular
      exercise received 2 PET scans with [11C]raclopride on 2 separate days, 1 at
      baseline and 1 at 5-10 min after running on a treadmill for 30 min. The speed and
      inclination of the treadmill were increased gradually to reach a maximal speed of
      9.7 km/h (6 mph) and a maximal inclination of 10degrees. Data were acquired on a
      Siemens HR+ scanner in 3-dimensional mode for 60 min. Heart rates and
      electrocardiograms were monitored. DA D2 receptor availability was measured using
      the ratio of the distribution volume in the putamen to that in the cerebellum,
      which is a function of the number of available binding sites/dissociation
      constant. RESULTS: The subjects ran at an average speed of 8.7 +/- 0.5 km/h (5.4
      +/- 0.3 mph) and at an inclination of 3.3degrees +/- 2degrees. The maximum effort
      of running was maintained for 10-15 min. The heart rates of the subjects were
      increased by 143% +/- 47%. DA D2 receptor availability in the putamen after
      treadmill running (4.22 +/- 0.34) was no different from that of baseline (4.17 +/
      0.29; P < 0.6). CONCLUSION: No significant changes in synaptic DA concentration
      were detected, although the subjects exercised vigorously for 30 min.

PMID- 10945527
TI  - Evaluation of brain metabolism in steno-occlusive carotid artery disease by
      proton MR spectroscopy: a correlative study with oxygen metabolism by PET.
AB  - Carotid occlusive diseases may cause ischemic changes in both the gray matter and
      the white matter as a result of hemodynamic compromise. To validate the use of
      proton magnetic resonance spectroscopy (MRS) in evaluating the carotid occlusive
      diseases, we compared changes in peaks of choline, in the sum of creatine and
      phosphocreatine, and in N-acetyl-aspartate (NAA) of the white matter with
      cortical oxygen metabolism measured by PET. METHODS: Eleven patients with
      unilateral steno-occlusive carotid artery disease underwent PET and MRS. Ten age
      matched healthy volunteers underwent MRS. No subjects had cortical infarction.
      MRS was performed bilaterally in the centrum semiovale. Regional blood flow,
      regional metabolic rate of oxygen (rCMRO2), and regional oxygen extraction
      fraction (rOEF) of the cerebral cortex were measured by the steady-state method
      with 15O gas. RESULTS: The asymmetry index of the ratio of NAA to the sum of
      creatine and phosphocreatine (NAA/Cr) correlated positively with the asymmetry
      index of rCMRO2 (r = 0.77; P < 0.01). Because rCMRO2 is a marker of tissue
      viability, the NAA/Cr of the centrum semiovale may reflect viable neuronal cells.
      The asymmetry index of the ratio of choline to the sum of creatine and
      phosphocreatine (Cho/Cr) showed a significant positive correlation with the
      asymmetry index of rOEF (r = 0.65; P < 0.05). All but 1 patient with an increased
      Cho/Cr (>1.03) showed an increase in rOEF of the ipsilateral cortex (>0.56). This
      finding may indicate membrane damage caused by ischemia, because the centrum
      semiovale is the deep watershed zone. CONCLUSION: The metabolic changes in the
      centrum semiovale detected by proton MRS reflect a hemodynamically compromised
      state and are useful in evaluating tissue viability.

PMID- 10945528
TI  - Comparing MRS and PET.

PMID- 10945529
TI  - Image fusion using an integrated, dual-head coincidence camera with X-ray tube
      based attenuation maps.
AB  - The purpose of this study was to characterize a dual-head gamma camera capable of
      FDG imaging using coincidence detection and equipped with an integrated x-ray
      transmission system for attenuation correction, anatomic mapping, and image
      fusion. METHODS: Radiation dose (425 mrads skin dose) and tissue contrast (0.7%
      deviation from expected values) were assessed for the x-ray system. Registration
      of transmission and emission scans was validated using a hot sphere phantom and
      was verified in selected patient studies. RESULTS: Fusion of anatomic maps and
      FDG images allowed precise anatomic localization of lesions identified using dual
      head coincidence imaging. CONCLUSION: The combined approach of x-ray attenuation,
      anatomic mapping, and image fusion with scintigraphic studies provides a new
      diagnostic tool for nuclear medicine and fertile ground for future research.

PMID- 10945531
TI  - Adding structure to function.

PMID- 10945530
TI  - A combined PET/CT scanner for clinical oncology.
AB  - The availability of accurately aligned, whole-body anatomical (CT) and functional
      (PET) images could have a significant impact on diagnosing and staging malignant
      disease and on identifying and localizing metastases. Computer algorithms to
      align CT and PET images acquired on different scanners are generally successful
      for the brain, whereas image alignment in other regions of the body is more
      problematic. METHODS: A combined PET/CT tomograph with the unique capability of
      acquiring accurately aligned functional and anatomical images for any part of the
      human body has been designed and built. The PET/CT scanner was developed as a
      combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating
      ECAT ART PET scanner. All components are mounted on a common rotational support
      within a single gantry. The PET and CT components can be operated either
      separately, or in combined mode. In combined mode, the CT images are used to
      correct the PET data for scatter and attenuation. Fully quantitative whole-body
      images are obtained for an axial extent of 100 cm in an imaging time of less than
      1 h. When operated in PET mode alone, transmission scans are acquired with dual
      137Cs sources. RESULTS: The scanner is fully operational and the combined device
      has been operated successfully in a clinical environment. Over 110 patients have
      been imaged, covering a range of different cancers, including lung, esophageal,
      head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and
      CT images are used both for diagnosing and staging disease and for evaluating
      response to therapy. We report the first performance measurements from the
      scanner and present some illustrative clinical studies acquired in cancer
      patients. CONCLUSION: A combined PET and CT scanner is a practical and effective
      approach to acquiring co-registered anatomical and functional images in a single
      scanning session.

PMID- 10945532
TI  - Assessment of infarct size and severity by quantitative myocardial SPECT: results
      from a multicenter study using a cardiac phantom.
AB  - The aim of this study was to determine the reproducibility of measurements of the
      size and severity of myocardial defects from 99mTc sestamibi cardiac phantom
      studies performed on multiple different gamma camera systems. METHODS: A total of
      250 gamma camera systems were evaluated over a 5-y period as part of the
      validation process of multiple multicenter trials. Each laboratory performed 9
      acquisitions of a cardiac phantom. Small myocardial defects (0%-30% of myocardial
      mass) were placed in the inferobasal region, whereas larger defects (40%-70%)
      were located in the anterior wall. Five representative short-axis slices were
      analyzed to determine defect size and severity (i.e., contrast in defect region)
      using circumferential short-axis count profiles. Defect size and severity were
      analyzed as a function of the type of collimator, gamma camera system, and type
      of orbit (180degrees versus 360degrees). RESULTS: Of the 250 systems, image data
      were acquired correctly and showed an acceptable correlation between true and
      measured defect size in 198 systems. For these systems, the slope of the
      regression line between true and measured defect size was 1.03 +/- 0.03, with an
      average absolute error in estimating defect size of 1.7% +/- 0.5% and a
      correlation coefficient r = 0.99 +/- 0.01. Results were independent of the gamma
      camera system, type of collimator, and orbit. Contrast in the defect region
      (minimum count/maximum count) showed a small dependence on collimator resolution
      and pixel size but was altered significantly by the type of acquisition orbit,
      with a 360 degrees orbit showing better contrast for defects located in the
      inferobasal wall than a 180degrees orbit. CONCLUSION: Measurement of defect size
      is independent of the gamma camera system, type of collimator, and orbit.
      Contrast in small defects located in the inferobasal wall of the heart is
      affected significantly by the type of acquisition orbit but not by the type of
      collimator.

PMID- 10945533
TI  - Comparing filtered backprojection and ordered-subsets expectation maximization
      for small-lesion detection and localization in 67Ga SPECT.
AB  - Iterative reconstruction of SPECT images has recently become clinically available
      as an alternative to filtered backprojection (FBP). However, there is conflicting
      evidence on whether iterative reconstruction, such as with the ordered-subsets
      expectation maximization (OSEM) algorithm, improves diagnostic performance over
      FBP. The study objective was to determine if the detection and localization of
      small lesions in simulated thoracic gallium SPECT images are better with OSEM
      reconstruction than with FBP, both with and without attenuation correction (AC).
      METHODS: Images were simulated using an analytic projector acting on the
      mathematic cardiac torso computer phantom. Perfect scatter rejection was assumed.
      Lesion detection accuracy was assessed using localization receiver operating
      characteristic methodology. The images were read by 5 nuclear medicine
      physicians. For each reconstruction strategy and for each observer, data were
      collected in 2 viewing sessions of 100 images. Two-way ANOVA and, when indicated,
      the Scheffe multiple comparisons test were applied to check for significant
      differences. RESULTS: Little difference in the accuracy of detection or
      localization was seen between FBP with and without AC. OSEM with AC extended the
      contrast range for accurate lesion detection and localization over that of the
      other methods investigated. Without AC, no significant difference between OSEM
      and FBP reconstruction was detected. CONCLUSION: OSEM with AC may improve the
      detection and localization of thoracic gallium-labeled lesions over FBP
      reconstruction.

PMID- 10945534
TI  - Relative impact of scatter, collimator response, attenuation, and finite spatial
      resolution corrections in cardiac SPECT.
AB  - We determined the relative effect of corrections for scatter, depth-dependent
      collimator response, attenuation, and finite spatial resolution on various image
      characteristics in cardiac SPECT. METHODS: Monte Carlo simulations and real
      acquisition of a 99mTc cardiac phantom were performed under comparable
      conditions. Simulated and acquired data were reconstructed using several
      correction schemes that combined different methods for scatter correction (3
      methods), depth-dependent collimator response correction (frequency-distance
      principle), attenuation correction (nonuniform Chang correction or within an
      iterative reconstruction algorithm), and finite spatial resolution correction
      (use of recovery coefficients). Five criteia were considered to assess the effect
      of the processing schemes: bull's-eye map (BEM) uniformity, contrast between the
      left ventricle (LV) wall and the LV cavity, spatial resolution, signal-to-noise
      ratio (SNR), and percent errors with respect to the known LV wall and liver
      activities. RESULTS: Similar results were obtained for the simulated and acquired
      data. Scatter correction significantly improved contrast and absolute
      quantitation but did not have noticeable effects on BEM uniformity or on spatial
      resolution and reduced the SNR. Correction for the depth-dependent collimator
      response improved spatial resolution from 13.3 to 9.5 mm in the LV region,
      improved absolute quantitation and contrast, but reduced the SNR. Correcting for
      attenuation was essential for restoring BEM uniformity (78% and 89% without and
      with attenuation correction, respectively [ideal value being 100%]) and accurate
      absolute activity quantitation (errors in estimated LV wall and liver activity
      decreased from 90% without attenuation correction to approximately20% with
      attenuation correction only). Although accurate absolute activity quantitation
      was achieved in the liver using scatter and attenuation corrections only,
      correction for finite spatial resolution was needed to estimate LV wall activity
      within 10%. CONCLUSION: The respective effects of corrections for scatter, depth
      dependent collimator response, attenuation, and finite spatial resolution on
      different image features in cardiac SPECT were quantified for a specific
      acquisition configuration. These results give indications regarding the
      improvements to be expected when using a specific processing scheme involving
      some or all corrections.

PMID- 10945535
TI  - Detection of reperfusion injury using PET in a monkey model of cerebral ischemia.
AB  - Several studies of focal ischemia and reperfusion in animal models have proposed
      that reperfusion contributes to brain damage. However, the extent to which
      reperfusion affects the brain, especially in acute stroke patients, remains
      unclear. Our purpose in this study was to determine whether reperfusion injury
      can be detected with PET and to clarify the extent to which reperfusion
      contributes to brain damage. METHODS: The right middle cerebral artery (MCA) of
      cynomolgus monkeys was occluded for 3 h (n = 8) or permanently (n = 5) by a
      transorbital device. Four consecutive PET studies were performed to assess
      cerebral blood flow (CBF), oxygen extraction fraction (OEF), and the cerebral
      metabolic rate of oxygen (CMRO2). RESULTS: The extent of necrotic brain damage 8
      h after MCA occlusion was significantly (P < 0.05) greater in the transient model
      than in the permanent model. Cortical damage was greater in the transient model.
      The MCA occlusion decreased CBF and CMRO2 in deep MCA territory and increased OEF
      in the cortex. In the permanent model, these changes continued throughout the
      experiment. In the transient model, the reperfusion induced postischemic
      hyperperfusion in the cortex, which showed necrotic damage at the end of the
      experiment. In this area, OEF and CMRO2 were decreased by reperfusion.
      CONCLUSION: The results suggest that reperfusion may strongly contribute to
      cortical damage. PET studies revealed that reperfusion decreased OEF and CMRO2 in
      the hyperperfused cortex. These changes may indicate reperfusion injury.

PMID- 10945536
TI  - Radiolabeled neuronal nitric oxide synthase inhibitors: synthesis, in vivo
      evaluation, and primate PET studies.
AB  - The objectives of this study were to synthesize neuronal nitric oxide synthase
      (NOS-I)-selective imaging agents based on the 2 potent, selective inhibitors AR-R
      17443 [N-(4-((2-((phenylmethyl) (methyl)-amino)ethyl)phenyl)-2
      thiophenecarboximidamide)] and AR-R 18512 [(N(2-methyl-1,2,3,4
      tetrahydroisoquinoline-7-yl)-2-thiophenecarboxim idamide)] in positron-emitting
      form and to evaluate regional brain uptake in rodents and primates. METHODS:
      [11C]AR-R 17443 and [11C]AR-R 18512 were produced by N-alkylation of the
      corresponding desmethyl precursors using [11C]iodomethane. Regional brain uptake
      of [11C]AR-R 17443 and [11C]AR-R 18512 was assayed in rats and NOS-I knockout
      mice, and PET was performed in baboons. Tracer kinetic modeling used a 2
      compartment plasma and brain tissue model. RESULTS: Yields of [11C]AR-R 17443 and
      [11C]AR-R 18512 ranged from 8% to 16% at the end of synthesis, with specific
      activities of 50-178 GBq/micromol (1,350-4,800 Ci/mmol) at the end of synthesis.
      In rat cerebellum and cortex at 30 min after injection, [11C]AR-R 17443 showed
      1.01 +/- 0.01 and 1.63 +/- 0.12 percentage injected dose per gram (%ID/g) uptake,
      respectively, whereas [11C]AR-R 18512 showed 0.88 +/- 0.01 and 1.30 +/- 0.07
      %ID/g uptake, respectively. Attempts to block tracer uptake by pretreatment with
      the NOS-I-selective inhibitor 7-nitroindazole or the corresponding unlabeled
      inhibitor (or desmethyl precursor to AR-R 17443 of similar potency) were
      unsuccessful. A small but significant (20%) decrease in cerebellar uptake of
      [11C]AR-R 18512 was present in NOS-I knockout mice compared with control mice.
      PET of [11C]AR-R 18512 in baboons with concurrent regional cerebral blood flow
      (rCBF) determination before and after administration of blocker showed dose
      related decreases in cerebellar uptake that were greater than or equal to
      decreases in rCBF. Plasma metabolites accounted for 27% of total activity at 30
      min after injection. Kinetic modeling of binding potentials revealed a
      distribution volume of 334 in cerebral blood that dropped 51% after blocker
      administration. CONCLUSION: Rodent studies for [11C]AR-R 17443 and [11C]AR-R
      18512 showed little evidence of specific NOS-I binding. In baboons, we detected a
      higher uptake of [11C]AR-R 18512 in the cerebellum than in the cortex
      (approximately 5%, accounting for decreased rCBF because of blockade), indicating
      minimal specific binding. Analogs of higher affinity are likely required if this
      class of agents is to prove viable for PET.

PMID- 10945537
TI  - Detection of serial changes in absolute myocardial perfusion with 82Rb PET.
AB  - Serial changes in myocardial perfusion may represent an important marker of
      disease progression or regression or the effects of therapy for patients with
      coronary artery disease (CAD). Quantitative methods have not been developed for
      the assessment of serial changes in perfusion. The objective of this study was to
      use receiver operator characteristic (ROC) analysis to determine the sensitivity
      and specificity of direct paired comparisons (DPCs) to detect changes in absolute
      myocardial perfusion measured with 82Rb PET. METHODS: Repeated dynamic 82Rb PET
      scans were obtained on 8 dogs at rest and during hyperemia induced with
      dobutamine (n = 4) or atrial pacing (n = 4). Radiolabeled microspheres were used
      to verify perfusion changes. Polar maps of absolute 82Rb retention and associated
      SD were estimated from the dynamic images. Paired comparisons were then performed
      using a t test on each of the 532 polar map sectors. Rest-rest and stress-stress
      differences were used to assess specificity and reproducibility, and stress-rest
      differences were used to assess sensitivity. RESULTS: 82Rb retention differences
      of 20% over baseline were detected with 85%-90% sensitivity and specificity,
      using the optimal DPC probability value and image smoothness. The average 82Rb
      retention differences correlated well with microspheres (r = 0.74; P = 0.001).
      Reproducibility of the mean retention values was 4.7% +/- 2.1%. As
      reproducibility varies, the DPC probability value can be adjusted to maintain
      specificity. These ROC results are directly applicable to other image modalities
      that produce measurements with similar SEs (3.7% +/- 0.9%). CONCLUSION: The
      developed method of DPCs is sensitive and specific for the detection of changes
      in absolute myocardial perfusion measured with 82Rb PET.

PMID- 10945538
TI  - Validation of the Yale circumferential quantification method using 201Tl and
      99mTc: a phantom study.
AB  - The Yale circumferential quantification (Yale CQ) method for quantification of
      SPECT images has been validated previously using empirically derived correction
      factors. In the present studies, the Yale CQ method was further validated using 2
      SPECT gamma cameras and 2 radioisotopes. METHODS: SPECT images were acquired from
      cardiac phantoms with multiple fillable inserts to simulate myocardial perfusion
      defects of varying extents and severities. Seventy phantom configurations were
      created. One hundred and forty SPECT images (70 with 99mTc and 70 with 201TI)
      were acquired using a triple-head SPECT camera. SPECT defects were quantified
      using the Yale CQ method, with incorporation of 99mTc- and 201TI-derived normal
      databases and correction factors. RESULTS: Quantified phantom SPECT defect sizes
      acquired with 99mTc correlated well with actual calculated defect sizes (r =
      0.96, y = 0.92x - 0.41). Bland-Altman analysis of agreement revealed strong
      agreement over a wide range of defect sizes, with a mean error of 1.2% and 2 SDs
      of 5.0%. Overall 201TI SPECT defect sizes also correlated well with actual defect
      sizes (r = 0.92), but there was a systematic underestimation (y = 0.72x - 0.76).
      Bland-Altman analysis showed underestimation over the entire range of defect
      sizes, with a mean error of 3.4% and 2 SDs of 7.5%. Implementation of a normal
      201TI phantom database improved accuracy of quantification (r = 0.95, y = 0.87x -
      1.36). The addition of 201TI-specific correction factors further improved
      accuracy (r= 0.94, y = 0.98x - 1.52). Reproducibility of SPECT defect sizes
      quantification for 99mTc using 2 gamma cameras was excellent (r = 0.98, y = 0.98x
      + 0.84). CONCLUSION: The Yale CQ SPECT quantification method, using the
      empirically derived correction factors, provides accurate and reproducible
      quantification of phantom defects over a wide range of defect sizes. Accurate
      quantification of 201TI and 99mTc SPECT defect sizes requires radiotracer
      specific normal databases.

PMID- 10945539
TI  - Loss of 123I-metaiodobenzylguanidine uptake by the heart in Parkinson's disease.

PMID- 10945540
TI  - Small-animal PET cameras.

PMID- 10945541
TI  - Procedure guideline for gastric emptying and motility.

PMID- 10945542
TI  - Prognostic value of FDG PET imaging in malignant pleural mesothelioma.

PMID- 10945543
TI  - Functional electrical stimulation: a new horizon for quadriplegic patients.

PMID- 10945544
TI  - The changing role of radiation therapy in the management of rectal cancer.

PMID- 10945545
TI  - Laparoscopic cholecystectomy: evaluating the effect of decreasing length of stay.

PMID- 10945546
TI  - Rectal cancer: changing patterns of referral for radiation therapy 1982-1997.
AB  - BACKGROUND: The purpose of the present study was to evaluate the changing role of
      radiation therapy in rectal cancer and to determine the patterns of referral of
      patients during a 15-year period. METHODS: From 1982 to 1997, 464 patients with
      carcinoma of the rectum were referred to the Department of Radiation Oncology,
      Royal Prince Alfred Hospital: 79% of patients had locoregional disease alone and
      21% had distant metastasis. Radiation therapy consisted of irradiation
      (definitive or palliative) alone to the primary tumour in 9.7% of cases;
      preoperative radiation in 7.3% of cases: preoperative chemoradiation in 7.5% of
      patients: postoperative radiation in 15.3% of patients: postoperative
      chemoradiation in 12.31% of patients: treatment of pelvic recurrence in 23.5% of
      patients and treatment of metastases in 9.1% of patients. The remainder were
      treated elsewhere (1.9%) or not treated (13.4%). RESULTS: There was an average
      annual 14% increase in referrals over the accrual period. Recurrent rectal cancer
      decreased from approximately 30% of referrals during 1982-91 to approximately 10%
      in 1995-7. The use of postoperative adjuvant radiation reached a peak of 50% in
      1993. The use of preoperative radiation increased suddenly in 1994 from < 10% to
      a sustained rate of approximately 30% of referrals. The use of chemoradiation
      commenced in 1990 for postoperative adjuvant treatment and in 1994 for
      preoperative treatment. The median survival time from initial diagnosis was 35
      months, with 2- and 5-year survival rates of 62 and 28%, respectively. Survivals
      at 5 years for patients treated with preoperative and postoperative radiation
      (with or without chemotherapy) and with recurrent disease were 56, 44 and 21%,
      respectively. CONCLUSIONS: The present study illustrates the changing role of
      radiation therapy in the management of rectal cancer. The increase in referrals
      over the observation period was due to increased multidisciplinary input into the
      initial management of these patients, based on reported clinical trials. The
      steady increase in the use of adjuvant therapy has paralleled a decrease in
      referrals for treatment of recurrence and reflects current clinical results. The
      sequencing of adjuvant therapy is changing currently, with greater emphasis on
      preoperative adjuvant treatment. Currently most adjuvant therapy includes
      chemotherapy.

PMID- 10945547
TI  - Colonic J pouch reconstruction of the radiation-damaged neorectum.
AB  - BACKGROUND: Postoperative radiotherapy after restorative resection for rectal
      carcinoma can cause fibrosis, stricture and proctitis. There are few accounts in
      the literature of the surgical approach to the radiation-damaged neorectum.
      METHODS: Reported are four patients who underwent resection of the radiation
      damaged neorectum with colonic J pouch reconstruction between September 1996 and
      July 1997. The operative and postoperative course is described. Parameters of
      bowel function were assessed by standardized interview 6 months after ileostomy
      reversal. Ongoing follow up has occurred to the present time. RESULTS: There was
      no mortality. Complications were splenic injury requiring splenectomy and a
      pelvic collection requiring percutaneous drainage. At 6 months after ileostomy
      reversal all patients had ongoing disturbance of bowel function, and two patients
      described some degree of incontinence. The mean frequency of bowel actions was
      four per day. Two patients have subsequently undergone further resection and
      formation of an end stoma. CONCLUSIONS: Resection of the radiation-damaged
      neorectum with colonic J pouch reconstruction is technically feasible. Functional
      results in the present series were disappointing and half the patients went on to
      formation of a permanent stoma.

PMID- 10945549
TI  - Early discharge following breast surgery: assessing care, support, and
      informational needs of women with early breast cancer in Australia.
AB  - BACKGROUND: The overall aims of the present study were to identify differences
      among women with early breast cancer who were discharged early from the hospital
      (within 48 h) and those who remained for routine admission in relation to
      demographic variables, informational needs, supportive needs, complications and
      satisfaction with care. METHODS: A random sample of 544 women diagnosed with
      early breast cancer was recruited to participate in a telephone survey via State
      and Territory cancer registries. RESULTS: Findings revealed little significant
      difference among women participating in early discharge and routine care in
      relation to demographics variables, informational needs, complication and
      satisfaction with care. Women participating in early discharge, however, were
      significantly less likely to be seen by a specialist breast care nurse or a
      volunteer with breast cancer. CONCLUSIONS: Prior to establishing early discharge
      as routine care, it is essential to establish clear health policy relating to
      early discharge and adequate follow-up services for women with breast cancer.

PMID- 10945548
TI  - Australian experience with the Freehand System for restoring grasp in
      quadriplegia.
AB  - BACKGROUND: The purpose of the present study was to document the value of an
      implanted multichannel neuroprosthesis (Freehand System) for restoring hand grasp
      in the first Australians to receive this device. METHODS: Hand function in C5
      quadriplegic patients was assessed via measurement of pinch forces, a grasp
      release test and tests of activities of daily living (ADL). Comparisons were made
      between presurgery scores and scores recorded after rehabilitation when the
      neuroprosthesis was and was not in use. RESULTS: A significant difference for
      both lateral pinch (P = 0.003) and palmar grasp (P = 0.003) was found between
      forces recorded with and without the use of the neuroprosthesis after
      rehabilitation, but not between forces recorded presurgery and during
      rehabilitation without the neuroprosthesis. All subjects were able to grasp, move
      and release more objects within the 30-s test period with the neuroprosthesis
      than without it. Collective results for the eight ADL tests for all six subjects
      show that, in 35 of the 48 (73%) occasions, less physical assistance and/or
      adaptive equipment was required when the Freehand system was employed compared to
      when it was not used. In 41 of the 48 (85%) occasions, the six subjects expressed
      a preference for using the neuroprosthesis to perform these activities of daily
      living. Twelve months after rehabilitation, five of the six subjects still used
      the neuroprosthesis daily or every second day. CONCLUSION: The Freehand
      neuroprosthesis has provided useful hand function with few surgical and technical
      difficulties in these patients. Regular ongoing use of the device indicates user
      satisfaction.

PMID- 10945550
TI  - A randomized controlled trial comparing cholecystocholangiography with cystic
      duct cholangiography during laparoscopic cholecystectomy.
AB  - BACKGROUND: The rate of intraoperative cholangiography fell after the advent of
      laparoscopic cholecystectomy due to the perceived difficulty of cystic duct
      cannulation. It is suggested that cholecystocholangiography (CCC) is a valid and
      easier alternative. The present study compares cystic duct cholangiography (CDC)
      to CCC with evaluation of procedural time, success rate, image quality, cost and
      radiation exposure. METHODS: Patients undergoing laparoscopic cholecystectomy
      were randomized to CCC (n = 40) or CDC (n = 36). Details of operative times,
      radiation exposure, and use of disposable equipment were recorded prospectively.
      Cholangiograms were performed using image intensification and were scored from 0
      to 6 according to adequacy of images. Data were analysed on an intention-to-treat
      basis with the chi-squared test, t-test or Fisher's exact test. RESULTS: The
      success rate for CDC was 100% and for CCC it was 72% (P = 0.0005). Patients with
      a failed CCC went on to have CDC for a success rate in the CCC arm of 92.5%.
      Comparing CDC to CCC, there was no significant difference in cost ($30.16 vs
      $33.36: P = 0.11), operative time (1 h 13 min vs 1 h 3 min; P = 0.19) or
      cholangiogram time (8 vs 9 min: P = 0.39). There was a significant difference in
      screening time (0:41 vs 1:33 min; P < 0.0001), adequate image quality (100 vs
      72.5%, P = 0.0005) and procedure-related complications (0 vs 5; P = 0.03).
      CONCLUSIONS: A significant number of CCC fail. Successful CCC provides inferior
      image quality and greater radiation exposure. It provides no benefit in time or
      cost and cannot be recommended for operative cholangiography.

PMID- 10945551
TI  - Grasper trauma during laparoscopic cholecystectomy.
AB  - BACKGROUND: The present study characterized the histopathological nature of
      laparoscopic grasper trauma during laparoscopic cholecystectomy in a prospective,
      blinded trial in order to establish a model for laparoscopic grasper trauma. The
      null hypothesis that graspers cause no histologically distinct tissue injury was
      tested. METHODS: The gall bladders of 19 patients undergoing laparoscopic
      cholecystectomy were examined. The area of gall bladder that had been grasped by
      Debakey laparoscopic forceps was excised (sample), along with an area of gall
      bladder that had not been grasped (control). Paired specimens were examined by a
      pathologist (blinded) to identify which was 'sample' and which was 'control' and
      to assess for histological markers of crushed tissue injury. The data were
      analysed by chi-squared or Fisher's exact tests. RESULTS: The pathologist was
      able to identify the sample (gripped) specimen in 13 of the 19 cases. In the
      remaining six cases the pathologist was unable to determine the specimen that had
      been gripped due to either absence of damage (four cases), or severe inflammation
      precluding assessment (two cases). The ability of the pathologist to distinguish
      the sample from the control specimen was significant (chi-squared test, P =
      0.003). Of the histological markers of crushed tissue injury, focal thinning of
      the gall bladder wall and epithelial loss were present in significantly more
      sample (gripped) specimens than control specimens (chi-squared test, P = 0.0002
      and P < 0.0001, respectively). CONCLUSIONS: Laparoscopic graspers cause tissue
      trauma that can be assessed histologically. The current study presents a
      relevant, reproducible, ethically acceptable human model for assessing the
      interaction between laparoscopic graspers and soft tissues.

PMID- 10945552
TI  - Laparoscopic Heller myotomy for achalasia.
AB  - BACKGROUND: Laparoscopic Heller myotomy provides similar results to open Heller
      myotomy for the treatment of oesophageal achalasia with the advantage of quicker
      recovery. The present series examines the evolution of operative technique,
      postoperative outcome and the effect of the 'learning curve' in a group of 70
      consecutive patients. METHODS: Between 1992 and 1999, details of all patients
      undergoing oesophagogastric myotomy for achalasia were prospectively entered on a
      database. Patients were followed with a biannual postal symptom questionnaire and
      scores were obtained for dysphagia, heartburn, regurgitation and chest pain.
      Comparison between preoperative and postoperative symptom scores, and case number
      and operative complications was made using Fisher's exact test or Mann-Whitney U
      test where appropriate. RESULTS: The indication for surgery was as a primary
      procedure in 20 cases; after failed endoscopic treatment in 48 cases; and after a
      'failed' fundoplication in two cases. Myotomy was combined with a 360 degrees
      fundoplication in 57 patients and with an anterior fundoplication in 13 patients.
      Mucosal perforation occurred intraoperatively in 11 cases. Conversion to an open
      procedure was required in seven patients. Seven patients required a second
      operation. At a mean follow up of 2.9 years, symptom scores were significantly
      improved from preoperative values for dysphagia, regurgitation and chest pain (P
      < 0.001). There was no increase in the postoperative score for heartburn. The
      'learning curve' contributed significantly to the length of the procedure, and
      the need for reoperation. CONCLUSIONS: Laparoscopic Heller myotomy is a
      technically challenging procedure that provides good early palliation of the
      symptoms associated with achalasia.

PMID- 10945553
TI  - Microsatellite instability and allelic imbalance in primary and secondary
      colorectal cancer.
AB  - BACKGROUND: Several studies of colorectal cancer have shown an association
      between the number and type of genomic defects and the stage of disease. A subset
      of colorectal tumours are due to inactivation of DNA mismatch repair genes and
      these tumours exhibit microsatellite instability. The aim of the present study
      was to compare and contrast the genomic defects present in both the primary and
      metastatic stages of the disease using microsatellite probes. METHODS:
      Modifications of the allelic profiles of 25 microsatellite regions were studied
      in a total of 85 colorectal tumours using fluorescent polymerase chain reaction
      (PCR) technology and subsequent direct analysis on an automatic sequencer. This
      approach was used because it allows the study of microsatellite instability and
      allelic imbalance. Stepwise logistic regression analysis was used to develop a
      model to predict whether the tumour was primary or secondary from the percentage
      of allelic imbalance. Subsequently, a group of 17 patients with primary
      colorectal tumours was analysed prospectively to test the proposed model.
      RESULTS: Six of 39 primary tumours showed microsatellite instability compared to
      0 of 29 liver metastases (P = 0.03). Primary tumours showed significantly less
      allelic imbalance than liver metastases (P < 0.001). Three probes (d18s53, d9s158
      and d10s191) were selected for use in a model to classify a tumour as primary or
      secondary on the basis of the degree of allelic imbalance. When tested
      prospectively this model had a specificity of 82%. CONCLUSIONS: The present study
      demonstrates the potential importance of using microsatellite probes both as a
      diagnostic tool and as a research technique to investigate the mechanisms of
      tumour progression. An important clinical finding is that none of the colorectal
      liver metastases showed microsatellite instability (0 of 29). This analysis also
      confirmed other work that has shown a direct relationship between the degree of
      allelic imbalance and the stage of disease.

PMID- 10945554
TI  - Appendicitis in the elderly.
AB  - BACKGROUND: Acute appendicitis in the elderly (i.e. those over 60 years of age)
      is associated with high morbidity and mortality rates. The present retrospective
      study reviews 10 years ( 1986-1996) of experience and outcome in treating acute
      appendicitis in patients aged 60 or above. METHODS: One hundred and thirty
      patients with acute appendicitis were identified and their case notes reviewed.
      RESULTS: Acute appendicitis was diagnosed at admission in 84 patients (64.6%).
      The remaining patients were observed for a median duration of 9.4 h prior to
      diagnosis and treatment. Patients with an underlying perforated acute appendix
      had a significantly longer period of pain prior to admission (P = 0.029; Mann
      Whitney U-test) but perforation per se was not associated with a significantly
      higher rate of morbidity and longer length of hospital stay. In contrast, the use
      of midline or paramedian incisions was associated with a higher wound infection
      rate (P=0.003; Pearson chi-squared test) and a longer hospital stay (P<0.001;
      Mann Whitney U-test). None of the patients were subsequently found to have an
      underlying colonic neoplasm. The overall morbidity rate was 28%. The mortality
      rate was 2.3% and all three patients who died had a severe comorbid medical
      condition prior to developing acute appendicitis. CONCLUSIONS: Acute appendicitis
      in the elderly is still associated with significant morbidity. But once acute
      appendicitis is diagnosed, then expedient surgery, appropriate use of
      perioperative antibiotics and a right lower quadrant incision can help to
      minimize the morbidity. Pre-existing severe comorbid medical condition(s) is a
      major contributory factor to mortality in these patients.

PMID- 10945555
TI  - Clinical review of the 'Snodgrass' hypospadias repair.
AB  - BACKGROUND: Snodgrass first described the tubularized, incised plate (TIP)
      urethroplasty for distal hypospadias repair in 1994 based on the concept of
      hingeing the incised urethral plate. The use of this technique allows a
      vertically orientated glanular meatus to be produced. A retrospective review of
      patients who had this procedure for the primary repair of distal hypospadias at
      New Children's Hospital was performed to objectively assess the cosmetic and
      functional outcomes of this technique. METHODS: All patients having a TIP
      urethroplasty for the primary repair of distal hypospadias between 1996 and 1998
      were requested to attend for review in an independent clinic. The parents were
      interviewed and the patient was examined to determine meatal location, meatal
      size, glanular configuration, urinary stream, straightness of erections,
      cosmesis, and the presence or absence of cutaneous sinus tracts or a urethral
      fistula. RESULTS: Sixty patients were identified. Forty-nine were reviewed in
      person, 10 were reviewed by telephone and one could not be traced. The median age
      at surgery was 13 months (range: 6-144 months), with a median follow up of 27
      months (range: 2-33 months). A glanular meatus was achieved in 57 patients (97%)
      and a conical glanular configuration was achieved in 58 patients (98%). The
      urinary stream and erections were straight in 54 (89%) and 58 patients (98%),
      respectively. Suture sinus tracts were present in 14 (24%) patients. Six patients
      (10%) developed a urethral fistula and three (5%) developed meatal stenosis. A
      good or satisfactory final cosmetic and functional result was achieved in 58
      patients (98%). CONCLUSIONS: The results of TIP urethroplasty are satisfactory at
      New Children's Hospital with the benefit of a cosmetic final outcome similar to a
      circumcised penis.

PMID- 10945556
TI  - Squamous carcinoma of the head and neck: molecular mechanisms and potential
      biomarkers.
AB  - Squamous cell carcinoma (SCC) of the head and neck remains a major health problem
      worldwide. Recent advances in cell biology suggest that cancer results from the
      accumulation of specific genetic mutations, many of which have now been
      identified. These mutations can cause the activation of genes that promote
      cellular proliferation or inhibit cell death (oncogenes), or they may inactivate
      genes that inhibit proliferation or promote cell death (tumour suppressor genes).
      Although there is no known set sequence of events leading to the formation of SCC
      of the head and neck, there is evidence that many of the genomic mutations
      implicated in other forms of cancer have an aetiological role in these tumours.
      Certain viruses, notably Epstein-Barr virus and some types of human
      papillomaviruses, are causally related to some head and neck cancers. There is
      now the prospect of using molecular markers to achieve earlier diagnosis and to
      aid in the prediction of both tumour behaviour and likely responses to particular
      treatment modalities.

PMID- 10945557
TI  - The safety of electrolytically induced hepatic necrosis in a pig model.
AB  - BACKGROUND: Electrolysis fulfils the criteria for an ideal treatment of patients
      with unresectable liver tumours. Previous studies in the rat and pig have shown
      that controlled necrosis can be safely produced by inserting platinum electrodes
      into normal liver' parenchyma and liver tumours. As with any new treatment it is
      mandatory to investigate the 'worst-case scenario' of inadvertent intravascular
      electrode placement in a large animal model before progressing to clinical
      trials. METHODS: Under ultrasound control in six pigs, electrodes were inserted
      into, or immediately adjacent to, an hepatic vein. An electrolytic 'dose' of 100
      C was then administered and the evolution of the lesion was monitored using
      ultrasound. Venous blood was collected before and during the electrolysis to
      evaluate potential acid/base disturbances and animals were closely monitored
      during electrolysis and during their recovery until a full autopsy was performed
      4-7 days after treatment. RESULTS: Gas bubbles were seen to enter the hepatic
      veins or interior vena cava during treatment in five of the six animals. There
      were no major complications as a consequence and all animals recovered and
      remained in a healthy state until they were killed. At autopsy one animal had
      complete thrombotic occlusion of the left hepatic vein. Otherwise, findings were
      normal. CONCLUSION: In the clinical setting, due to the use of ultrasound to
      guide electrode placement into the centre of a tumour, the electrodes should
      rarely juxtapose an hepatic vein. Nevertheless, in this extreme situation,
      electrolysis is surprisingly safe with only one major vascular occlusion and no
      morbidity or mortality.

PMID- 10945558
TI  - Ulcers in diabetic feet: an orthopaedic not a vascular problem.

PMID- 10945559
TI  - Duels, doctors and death.
AB  - Duelling as a method of settling disputes between gentlemen was practised in the
      British Isles and on the Continent from the 16th to the beginning of the 20th
      century. In early duels the victory would go to the better swordsman, but the use
      of pistols not only made the contest more deadly, but also more democratic. The
      social aspects, the indications for a challenge, the material and methods and the
      mortality and morbidity of the contest are considered. Mention is made of a case
      in which John Hunter was consulted. Its management, progress and autopsy findings
      are described together with Hunter's thoughts about it and the management of
      similar wounds.

PMID- 10945560
TI  - Laparoscopic cholecystectomy of a bifid gall bladder with two separate cystic
      ducts.

PMID- 10945561
TI  - Cat scratch disease presenting as splenic abscess.

PMID- 10945562
TI  - Understanding angiogenesis and its clinical applications.
AB  - Angiogenesis is the growth of new vessels from pre-existing blood vessels.
      Angiogenesis is critical during embryogenesis but occurs minimally in healthy
      adults, except in wound repair, inflammation, female reproductive organs, and
      pathologic conditions. Various growth factors and proteins, elements of the
      extracellular matrix, components of the coagulation/fibrinolytic system, and
      platelets interact with the endothelial cells and pericytes of blood vessels to
      regulate angiogenesis. Characterization of angiogenic factors has revealed that
      remodeling of the extracellular matrix occurs during angiogenesis, mediated by
      integrins that are found on the endothelial cell surface membrane. Counter
      regulatory antiangiogenic proteins and molecules that show an intricate balance
      in the regulation of angiogenesis have also been characterized. Components of the
      coagulation/fibrinolysis cascade also play a critical role in angiogenesis.
      Elucidation of the mechanisms of angiogenesis has led to better understanding of
      certain disease states. Ongoing studies are evaluating the stimulation of
      angiogenesis to treat ischemic disorders, and the inhibition of angiogenesis to
      prevent abnormal proliferation in malignant and non-malignant disorders.

PMID- 10945563
TI  - Prognostic factors in malignant gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors are a heterogeneous group of mesenchymal
      neoplasms of the gastrointestinal tract in which routine histopathological
      evaluation fails to reveal definitive evidence of differentiation. Given the
      heterogeneity in clinical presentation and the frequent morphological overlap,
      the biological behavior of these neoplasms is difficult to predict. We have
      evaluated, by Cox Proportional Hazards Regression Analysis, the
      clinicopathological features of 51 malignant gastrointestinal stromal tumors to
      identify predictors of survival. In the univariate analysis, survival inversely
      correlated with size, number of mitoses, and patient's age. In the multivariate
      analysis, only the degree of necrosis and phenotypic differentiation toward
      smooth muscle were found to be indicators of poor prognosis. Based on these
      results, a simple classification scheme for gastrointestinal stromal tumors is
      proposed. This classification appears to have great prognostic value for these
      tumors, and may be useful in guiding therapeutic management.

PMID- 10945564
TI  - HER-2/neu protein-receptor-positive breast carcinoma: an immunologic perspective.
AB  - Immunotherapy using a monoclonal antibody against the human epidermal growth
      factor receptor 2 protein, HER-2/neu, has proven to be clinically efficacious in
      about one-half of breast cancer patients who exhibit strong (3+) plasmalemmal
      immunoreactivity for this protein. The tumoricidal effect of this antibody relies
      in part upon antibody-dependent cell-mediated cytotoxicity. This report provides
      observations on certain factors or circumstances which could have an impact on
      this aspect of the therapeutic approach. These include: (1) concurrent
      medications; (2) the composition (immunophenotype) of peritumoral lymphocytes and
      the generally limited numbers of intratumoral T-lymphocytes/natural killer (NK)
      cells, monocytes, and neutrophilic granulocytes; (3) the presence of circulating
      HER-2/neu antigens which might bind the exogenous antibody and lead to immune
      complex formation; (4) the variable co-expression in the tumor of cytokines known
      to downregulate NK cell function (ie, transforming growth factor-beta1 [TGF
      beta1] and platelet-derived growth factor [PDGF]-AB); and (5) the tumoral and/or
      stromal immunoreactivity for angiotensin-converting enzyme, which forms a part of
      one of the pathways for the activation of latent TGF-beta1 and for the
      biosynthesis of PDGF-AB. These observations provide an immunologic perspective
      for the use of monoclonal antibody therapy in HER-2/neu protein-receptor-positive
      breast carcinoma and suggest a role for the clinical laboratory in identifying
      potential avenues for additional manipulations of the immune system in individual
      cases in order to enhance the therapeutic response.

PMID- 10945565
TI  - Assessment of Her-2/neu overexpression in primary breast cancers and their
      metastatic lesions: an immunohistochemical study.
AB  - Since the development of novel immunotherapy using Herceptin as the first agent
      specifically indicated for HER-2/neu overexpression in metastatic breast cancer,
      there has been interest in using HercepTest as a predictor of response to such
      therapy. There is debate whether it is justifiable to perform HercepTest on every
      newly diagnosed breast cancer, since only approximately 43% of the cases will
      have related metastatic disease, and Herceptin is indicated only for breast
      cancer with metastatic disease. It may be more cost-effective to limit HercepTest
      to the related metastatic lesions. Therefore, it is important to assess whether
      the pattern of HER-21neu overexpression of metastatic breast cancer is also
      present in the primary lesion. HercepTest was performed on formalin-fixed,
      paraffin-embedded tissue sections of 56 primary breast cancers and their
      corresponding metastatic lesions. The protocol and scoring guidelines recommended
      by the manufacturer were followed. Tissue sections (5 microm) of a primary and
      the metastatic lesion from the same case were placed parallel on a single glass
      slide. The pattern and intensity of HER-2/neu overexpression (32%) in the primary
      and metastatic lesions were found to be nearly identical. Heterogeneity was
      observed in only one case. The score of primary cancer was 3+, and the metastatic
      lesion was 2+. Both were reported as positive. Intratumor heterogeneity (1+ to
      3+) was also noted in two (4%) cases. However, the same pattern was found in both
      the primary and related metastatic lesions. The nearly identical HercepTest
      results in the primary and metastatic lesions suggest the potentiality of
      limiting the HercepTest to breast cancer-related metastases. Currently, any
      superficial and most deep-seated metastatic lesions can be easily sampled by fine
      needle aspiration biopsy or core biopsy, providing adequate samples for
      HercepTest. Eliminating unnecessary use of the HercepTest may provide a cost
      effective alternative approach to the management of breast cancer patients.

PMID- 10945566
TI  - Tenascin patterns of expression in duct carcinoma in situ of the breast.
AB  - Immunohistochemical methods were used to study tenascin (TN) expression in duct
      carcinoma in situ (DCIS) of the breast of different histologic types. We
      evaluated 82 lumpectomy specimens of DCIS. There were 5 cases of comedo type, 19
      cases of noncomedo type, and 58 cases of mixed comedo and noncomedo type. In 44
      cases, the intraductal carcinomas were associated with infiltrating (invasive)
      duct carcinoma. TN expression was studied by immunohistochemical methods using
      monoclonal mouse anti-human tenascin (DAKO-TN2M636; 1:50 dilution). Positivity
      was recorded on a scale of 0 to 2+ for presence of TN staining around tumor ducts
      and thickness of TN-stained fibrous bands. TN showed positive correlation between
      thick bands around comedo DCIS and thin bands around noncomedo DCIS. The TN score
      had statistically significant positive association with high nuclear grade (p
      0.004), periductal inflammatory infiltrate of DCIS (p 0.0006), associated
      extensive central necrosis of DCIS (p 0.0005), and comedo DCIS (p 0.0004). TN
      expression in the stroma was positively associated with tumor size (p 0.00002),
      extensive central necrosis (p 0.02), comedo DCIS (p 0.0005), and associated
      invasive carcinoma (p 0.006). The TN score did not correlate with duct size,
      multicentric carcinoma, or associated microcalcification. These results
      demonstrate the different biological nature of DCIS comedo type and suggest its
      preinvasive potential.

PMID- 10945567
TI  - Giant cell reparative granuloma of the small bones of the hands and feet: a
      report of three cases.
AB  - Giant cell reparative granuloma (GCRG) involving the small tubular bones of the
      hands and feet is a rare entity that can have a wide range of morphologic
      presentations and can be confused with more aggressive tumors. Awareness of this
      lesion is important to avoid diagnostic errors and potential mismanagement. We
      report three cases of GCRG that involve the small tubular bones of the hands and
      feet, with long-term follow-up periods that confirm a benign course. Previous
      reports included the differential diagnosis of giant cell tumor, brown tumor of
      hyperparathyroidism, aneurysmal bone cyst, and non-ossifying fibroma. The
      presence of chondroid material in two of our cases, one of which also shows
      atypical nuclei and a periosteal reaction, expands the differential diagnosis to
      include bone- and cartilage-forming neoplasms.

PMID- 10945568
TI  - Castleman's disease confined to the leptomeninges.
AB  - We report a rare case of the plasma cell variant of Castleman's disease confined
      to the leptomeninges in a 42-year-old female. Flow cytometry demonstrated a minor
      monoclonal kappa light chain population, and conventional Southern blotting
      confirmed clonal rearrangement of the J(H) immunoglobulin heavy-chain gene.
      Polymerase chain reaction for Epstein-Barr virus and Kaposi's sarcoma-associated
      herpes virus was negative. The patient is disease-free five years after surgical
      resection. To our knowledge, clonal gene rearrangement has not been previously
      reported in the plasma cell variant of localized intracranial Castleman's
      disease.

PMID- 10945570
TI  - The incidence and significance of pseudoparaproteins in a community hospital.
AB  - Pseudoparaproteins were observed in 129 (10.5%) of 1,229 high resolution protein
      electrophoretic fractionations of serum (N = 847), urine (N = 368), or
      cerebrospinal fluid (N = 14) performed in this laboratory during a 12-month
      period. The pseudoparaproteins identified in serum electrophoretic patterns
      included fibrinogen, C-reactive protein, hemoglobin-haptoglobin complex, elevated
      beta-globulins (transferrin and C3), lysozyme (muramidase), and an extended
      migration artifact. In the electrophoretic patterns of urine, the
      pseudoparaproteins consisted of nonspecific gamma zone bands of varying
      intensity. Gamma zone trace protein in the cerebrospinal fluid was often of
      sufficient intensity to cause potential confusion with oligoclonal bands.
      Awareness of the characteristic electrophoretic migration positions of these
      pseudoparaproteins helps to avoid unnecessary ancillary testing and expense.

PMID- 10945569
TI  - A case of aggressive multiple myeloma with cleaved, multilobated, and monocytoid
      nuclei, and no serum monoclonal gammopathy.
AB  - Multiple myeloma is a B-cell malignancy characterized by proliferation of
      neoplastic plasma cells. A few cases have been reported identifying variant forms
      of neoplastic plasma cells with atypical nuclei that secrete myeloma protein. We
      report a highly unusual case of plasma cell myeloma that presented with cleaved,
      multilobated, and monocytoid nuclei, without detectable myeloma protein in the
      serum or urine. The bone marrow contained sheets of plasma cells exhibiting
      pleomorphic nuclei with cleaved, multilobated, and monocytoid features that were
      negative for myeloperoxidase and dual esterase. Flow cytometric analysis revealed
      CD38high/CD45low cells expressing cytoplasmic kappa light chain, without evidence
      of myeloid or lymphoid differentiation. Following chemotherapy, the patient
      developed secondary plasma cell leukemia. A high plasma cell labeling index was
      obtained from bone marrow and peripheral blood, indicating a poor prognosis. In
      addition to quantitative immunoglobulins, serum protein electrophoresis, and
      immunofixation electrophoresis of serum and urine, we recommend cytochemical and
      flow cytometric studies for evaluation of suspected plasma cell myeloma with
      atypical cellular features.

PMID- 10945572
TI  - Commentary: A medical reflection.

PMID- 10945571
TI  - Are metalloproteins and acute phase reactants associated with cardiovascular
      disease in end-stage renal failure?
AB  - End-stage renal failure (ESRF) is associated with a higher risk of cardiovascular
      disease (CVD) than predicted by the major risk factors. We investigate the
      hypothesis that metalloproteins such as transferrin and ceruloplasmin and the
      inflammatory response are associated with CVD risk in this population. In this
      cross-sectional study of 81 subjects stable on haemodialysis (HD), 43 with CVD
      and/or peripheral vascular disease (PAD) were compared to 38 subjects without
      clinical evidence of CVD/PAD. Serum concentrations of metalloproteins and acute
      phase reactants were compared by univariate analysis and logistic regression
      modelling. Body mass index, gender ratios, prevalence of diabetes, iron status,
      and homocysteine concentrations did not differ significantly between the groups.
      Those with CVD were older (P< 0.001) and had been on dialysis for longer (P =
      0.004). CVD subjects had significantly higher concentrations of ceruloplasmin
      (325 vs 284 mg/L, P = 0.011), copper (18.2 vs 15.7 micromol/L, P = 0.002), and C
      reactive protein (CRP) (median 9.0 vs 3.8 mg/L, P = 0.002). Transferrin iron
      binding capacity tended to be higher in the CVD group (P = 0.088). CVD risk for
      subjects with serum concentrations in the upper tertile was increased 9.4-fold
      (CI 2.8-31.0) for copper, 4.2-fold (CI 1.5-12.2) for ceruloplasmin, 3.9-fold (CI
      1.3-12.1) for transferrin iron binding capacity, and 2.3-fold (CI 0.9-6.1) for
      CRP. In multivariate logistic regression models, age (P = 0.001) and time on
      dialysis (P = 0.002) were the strongest risk factors for CVD. After adjustment
      for age and time on dialysis, transferrin iron binding capacity (P = 0.013) and
      copper (P = 0.019) continued to be associated with CVD risk but ceruloplasmin (P
      = 0.065) and CRP (P = 0.634) were not. Total cholesterol was associated with a
      lower risk of CVD (ie protective), presumably due to cholesterol-lowering therapy
      in high-risk patients. In conclusion, copper and transferrin iron binding
      capacity may be associated with CVD risk in HD subjects.

PMID- 10945573
TI  - UV inactivation, liquid-holding recovery, and photoreactivation of Escherichia
      coli O157 and other pathogenic Escherichia coli strains in water.
AB  - Drinking water, water used in food production and for irrigation, water for fish
      farming, waste water, surface water, and recreational water have been recently
      recognized as a vector for the transmission of pathogenic Escherichia coli,
      especially serotype O157:H7. We investigated the UV (253.7 nm) inactivation
      behavior and the capability of dark repair (liquid-holding recovery) and
      photoreactivation of seven pathogenic (including three enterohemorrhagic E. coli)
      strains and one nonpathogenic strain of E. coli (ATCC 11229) with respect to the
      use of UV light for water disinfection purposes. Because most bacteria and yeast
      are known to be able to repair UV damage in their nucleic acids, repair
      mechanisms have to be considered to ensure safe water disinfection. We found a
      wide divergence in the UV susceptibility within the strains tested. A 6-log
      reduction of bacteria that fulfills the requirement for safe water disinfection
      was reached for the very most susceptible strain O157:H7 (CCUG 29199) at a UV
      fluence of 12 J/m2, whereas for the most resistant strain, O25:K98:NM, a UV
      fluence of about 125 J/m2 was needed. Except for one strain (O50:H7) liquid
      holding recovery did not play an important role in recovery after UV irradiation.
      By contrast, all strains, particularly strains O25:K98:NM, O78:K80:H12, and
      O157:H7 (CCUG 29193), demonstrated photorepair ability. For a 6-log reduction of
      these strains, a UV fluence (253.7 nm) up to 300 J/m2 is required. The results
      reveal that the minimum fluence of 400 J/m2 demanded in the Austrian standard for
      water disinfection is sufficient to inactivate pathogenic E. coli. A fluence of
      160 J/m2 (recommendation in Norway) or 250 J/m2 (recommendation in Switzerland)
      cannot be regarded as safe in that respect.

PMID- 10945574
TI  - Heat inactivation of Escherichia coli O157:H7 in apple juice exposed to chlorine.
AB  - Exposure of Escherichia coli O157:H7 to chlorine before heat treatment results in
      increased production of heat shock proteins. Current heating regimens for
      pasteurizing apple cider do not account for chlorine exposure in the wash water.
      This research determined the effect of sublethal chlorine treatment on thermal
      inactivation of E. coli O157:H7. D58-values were calculated for stationary-phase
      cells exposed to 0.6 mg/liter of total available chlorine and unchlorinated cells
      in commercial shelf-stable apple juice (pH 3.6). D58-values for unchlorinated and
      chlorine-exposed cells in buffer were 5.45 and 1.65 min, respectively (P < 0.01).
      Death curves of chlorine-exposed and unchlorinated cells in apple juice were not
      completely linear. Unchlorinated cells heated in apple juice exhibit a 3-min
      delay before onset of linear inactivation. Chlorine treatment eliminated this
      shoulder, indicating an overall loss of thermotolerance. The linear portion of
      each curve represented a small fraction of the total population. D58-values
      calculated from these populations are 0.77 min for unexposed cells and 1.19 min
      for chlorine-exposed cells (P = 0.05). This indicates that a subpopulation of
      chorine-treated cells is possibly more resistant to heat because of chlorine
      treatment. The effect of chlorine treatment, however, is insignificant when
      compared with the effect of losing the shoulder. This is illustrated by the time
      required to kill the initial 90% of the cell population. This is observed to be
      3.14 min for unchlorinated versus 0.3 min for chlorine-exposed cells (P < 0.001).
      These observations indicate that current heat treatments need not be adjusted for
      the effect of chlorine treatment.

PMID- 10945575
TI  - Heat inactivation of Escherichia coli O157:H7 in apple cider containing malic
      acid, sodium benzoate, and potassium sorbate.
AB  - The effect of pH modification and preservative addition in apple cider on the
      heat resistance of Escherichia coli O157:H7 was investigated. E. coli O157:H7 and
      various amounts of potassium sorbate (0 to 0.2%), sodium benzoate (0 to 0.2%),
      and malic acid (0 to 1%) were added to apple cider. Thermal inactivation
      experiments were performed at 47, 50, and 53 degrees C, and D- and z-values were
      calculated. In apple cider without additives, the D-value at 50 degrees C (D50)
      was about 65 min, but addition of preservatives and malic acid significantly (P <
      0.01) decreased D-values. D50-values decreased to 13.9 min in cider with 0.5%
      malic acid, 13.2 min with 0.1% sorbate, and 7.0 min with 0.1% benzoate added.
      Addition of both sorbate and malic acid had similar effects as either one alone,
      thus additive effects were not present. However, addition of both 0.2% benzoate
      and 1% malic acid did show additive effects, lowering D50 to 0.3 min. Addition of
      all three components (0.2% sorbate, 0.2% benzoate, and 1% malic acid) resulted in
      a D50 = 18 s. The z-value of cider without additives was about 6 degrees C,
      whereas z-values of cider containing malic acid, benzoate, and/or sorbate ranged
      from about 6 degrees C to 26 degrees C. This increase may result in a longer 5
      log reduction time at higher temperatures (i.e., 70 degrees C) in cider with
      benzoate as compared to cider without additives.

PMID- 10945576
TI  - A multiplex polymerase chain reaction assay for rapid detection and
      identification of Escherichia coli O157:H7 in foods and bovine feces.
AB  - A multiplex polymerase chain reaction (PCR) assay was designed to simplify
      detection of Escherichia coli O157:H7 and to identify the H serogroup and the
      type of Shiga toxin produced by this bacterium. Primers for a plasmid-encoded
      hemolysin gene (hly933), and chromosomal flagella (fliCh7; flagellar structural
      gene of H7 serogroup), Shiga toxins (stx1, stx2), and attaching and effacing
      (eaeA) genes were used in a multiplex PCR for coamplification of the
      corresponding DNA sequences from enterohemorrhagic E. coli (EHEC) O157:H7.
      Enrichment cultures of ground beef, blue cheese, mussels, alfalfa sprouts, and
      bovine feces, artificially inoculated with various levels of E. coli O157:H7
      strain 933, were subjected to a simple DNA extraction step prior to the PCR, and
      the resulting amplification products were analyzed by agarose gel
      electrophoresis. Sensitivity of the assay was < or = 1 CFU/g of food or bovine
      feces (initial inoculum level), and results could be obtained within 24 h.
      Similar detection levels were obtained with ground beef samples that underwent
      enrichment culturing immediately after inoculation and samples that were frozen
      or refrigerated prior to enrichment. The multiplex PCR facilitates detection of
      E. coli O157:H7 and can reduce the time required for confirmation of isolates by
      up to 3 to 4 days.

PMID- 10945577
TI  - Bactericidal effect of sodium chlorate on Escherichia coli O157:H7 and Salmonella
      typhimurium DT104 in rumen contents in vitro.
AB  - Escherichia coli O157:H7 and Salmonella Typhimurium DT104 are important foodborne
      pathogens affecting the beef and dairy industries and strategies are sought to
      rid these organisms from cattle at slaughter. Both pathogens possess respiratory
      nitrate reductase that also reduces chlorate to the lethal chlorite ion. Because
      most anaerobes lack respiratory nitrate reductase, we hypothesized that chlorate
      may selectively kill E. coli O157:H7 and Salmonella Typhimurium DT104 but not
      potentially beneficial anaerobes. In support of this hypothesis, we found that
      concentrations of E. coli O157:H7 and Salmonella Typhimurium DT104 were reduced
      from approximately 1,000,000 colony forming units (CFU) to below our level of
      detection (< or = 10 CFU) following in vitro incubation (24 h) in buffered
      ruminal contents (pH 6.8) containing 5 mM added chlorate. In contrast, chlorate
      had little effect on the most probable number (mean +/- SD) of total culturable
      anaerobes (ranging from 9.9 +/- 0.72 to 10.7 +/- 0.01 log10 cells/ml). Thus,
      chlorate was bactericidal to E. coli O157:H7 and Salmonella Typhimurium DT104 but
      not to potentially beneficial bacteria. The bactericidal effect of chlorate was
      concentration dependent (less at 1.25 mM) and markedly affected by pH (more
      bactericidal at pH 6.8 than pH 5.6).

PMID- 10945578
TI  - Rapid detection of Salmonella typhimurium in chicken carcass wash water using an
      immunoelectrochemical method.
AB  - An immunoelectrochemical method coupled with immunomagnetic separation was
      developed for rapid detection of Salmonella Typhimurium in chicken carcass wash
      water. Samples of chicken carcass wash water were inoculated with Salmonella
      Typhimurium at different cell numbers. Possible nonspecified inhibitors in the
      wash water were minimized by filtration and centrifugation. An approximately 9.4%
      loss of Salmonella cells was found after filtration (P < 0.01). The samples were
      mixed with anti-Salmonella-coated magnetic beads (ASCMB) and alkaline phosphatase
      labeled anti-Salmonella (APLAS) to form ASCMB-Salmonella-APLAS conjugates. The
      conjugates were separated from the solution using a magnetic separator and then
      incubated with phenylphosphate substrate to produce phenol. The number of
      Salmonella was determined by measuring the phenol concentration using an
      amperometric tyrosinase carbon paste electrode in a flow injection analysis
      system. Under optimized parameters (1 mM MgCl2, 0.2 microg/ml APLAS, and 1 mM
      phenylphosphate in pH 7.0 Tris buffer solution), Salmonella Typhimurium in
      chicken carcass wash water could be identified and enumerated within 2.5 h with a
      detection limit of 5 x 10(3) CFU/ml. A linear relationship on a log-log scale was
      found between Salmonella cell number and the peak current ratio for Salmonella
      concentrations ranging from 10(3) to 10(7) CFU/ml (R2 = 0.963). The peak currents
      of multibacteria samples, containing Salmonella Typhimurium, Listeria
      monocytogenes, and Campylobacter jejuni, were not significantly different from
      Salmonella-only samples (P > 0.01).

PMID- 10945579
TI  - Impact of acid on survival of Vibrio vulnificus and Vibrio vulnificus phage.
AB  - Three strains of Vibrio vulnificus and V. vulnificus phages were tested for acid
      sensitivity at 21 degrees C. V. vulnificus strain 304 was more resistant to pH
      4.0 than strains CVD-1 and A-9, whereas acid sensitivities of V. vulnificus
      strains at pH 3.0 and 2.0 were similar. V. vulnificus phage strain 110A-7 was
      more resistant to pH 4.0 than strain 153A-7, whereas acid sensitivities of phage
      strains at pH 3.5 and 3.0 were similar. Numbers of V. vulnificus and its phage
      were close to the limit of detection after 100 s at pH 2.0 and after 24 min at pH
      3.0. Acid D-values at 21 degrees C decreased as pH decreased for both V.
      vulnificus and phages. D-values of phage strains at pH 3.5 were 10-fold greater
      than those of host strain at pH 4.0. D-values of phage strains were slightly
      greater than those of host strain at pH 3.0. These results suggest that V.
      vulnificus and its phage were very sensitive to pH of less than 3.0, although V.
      vulnificus phages were more resistant to acid than their host.

PMID- 10945580
TI  - Survival of Yersinia enterocolitica and mesophilic aerobic bacteria on eggshell
      after washing with hypochlorite and organic acid solutions.
AB  - Populations of Yersinia enterocolitica 0:9 and mesophilic aerobic bacteria on the
      shell of fresh chicken eggs were assessed prior and after washing with 0.75%, 1%,
      and 3% acetic and lactic acids, 50, 100, and 200 mg/liter (ppm) of chlorine, and
      water. Highest reductions of mesophilic aerobic bacterial populations (normal
      flora) on trypticase soy agar were 1.28 and 2.15 log10 cycles with 100 and 200
      mg/liter of chlorine, 0.28 and 0.36 log10 cycles with 1% and 3% acetic acid, and
      0.70 and 0.71 log10 cycles with 1% and 3% lactic acid, respectively, as compared
      to the control group. No Salmonella or Yersinia were detected among the natural
      flora of the eggs. On Y. enterocolitica O:9-inoculated eggs, reductions of 2.66,
      2.77, and 2.92 log10 cycles by 50, 100, and 200 mg/liter of chlorine, of 2.47,
      2.48, and 2.49 log10 cycles by 0.75%, 1%, and 3% of acetic acid, and of 2.48 and
      2.72 log10 cycles with 1% and 3% of lactic acid, respectively, were observed with
      respect to the control. Organic acids at 3% caused detachment of the surface
      cuticle of the eggshell. Y. enterocolitica was more sensitive to the wash
      treatments than the natural microflora. The absence of potentially pathogenic Y.
      enterocolitica, observed for other fresh foods, should be a norm for fresh eggs
      sold in retail stores.

PMID- 10945581
TI  - Comparison of different reducing agents for enhanced detection of heat-injured
      Listeria monocytogenes.
AB  - The effect of different reducing agents (L-cysteine, Oxyrase, and Enterococcus
      faecium) and their combinations on the detection of heat-injured (62.8 degrees C,
      7.5 min or 10 min) Listeria monocytogenes was examined. The incorporation of L
      Cysteine (0.5 g/liter) yielded higher percentage detection than any of the other
      reducing agents (P < 0.05). The combination of Oxyrase (10 U/ml) and E. faecium
      (10(3) CFU/ml) synergistically enhanced the detection of L. monocytogenes heat
      injured for 10 min at 62.8 degrees C (P < 0.05). Simultaneous addition of L
      cysteine (0.5 g/liter) and Oxyrase (10 U/ml) significantly lowered the recovery
      of heat-injured L. monocytogenes (P < 0.05). Higher activities of Oxyrase (50
      U/ml) inhibited the detection of heat-injured L. monocytogenes (P < 0.05). The
      rates of depletion of relative percentage O2 were in the order: L-cysteine (0.5
      g/liter; 6.63%/ min) > Oxyrase (10 U/ml; 5.00%/min) > E. faecium (10(8) CFU/ml;
      1.66%/min) > E. faecium (10(3) CFU/ml; 0.20%/min). The final levels of redox
      potential (Eh) achieved were -110.5 mV, -100 mV, -83.5 mV, and -25 mV for E.
      faecium (10(8) CFU/ml), L-cysteine, Oxyrase, and E. faecium (10(3) CFU/ml),
      respectively.

PMID- 10945582
TI  - Feasibility of a defined microflora challenge method for evaluating the efficacy
      of foodborne Listeria monocytogenes selective enrichments.
AB  - Comparison of isolation methods for microbial pathogens is complicated by the
      variable interference caused by the competitive microflora present in test
      samples such as foods. In principle, using measured amounts of a standard
      competitor in a defined surrogate food matrix might control the effect of
      variable interference. This possibility was investigated using Listeria
      monocytogenes and enrichment broths belonging to the acriflavine-nalidixate
      selective agent class. Triplicate test sample sets were prepared. Each set
      consisted of suspensions of variable levels of the standard competitor,
      Enterococcus faecium strain 111 (approximately 10 to 10(9) CFU/25 g), mixed with
      a low constant level (10 to 100 CFU/25 g) of L. monocytogenes. These test samples
      were enriched at 30 degrees C for 48 h in different selective media and streaked
      onto selective isolation agars. The input CFU ratio (E. faecium/L. monocytogenes)
      that permitted a 50% end point L. monocytogenes recovery was 2.2 x 10(6) or
      higher for the Food and Drug Administration one-step enrichments and 0.8 x 10(6)
      for the International Standards Organization (ISO) two-step enrichment. These and
      other results show that this evaluation method is feasible with this class of
      enrichments. Interestingly, L. monocytogenes could be detected in enrichment
      cultures at high-input E. faecium/L. monocytogenes ratios even when the enriched
      samples were plated onto nonselective media. The pinpoint colonies of L.
      monocytogenes embedded in a confluent lawn of E. faecium 111 were detectable by
      their contrasting coloration in Henry obliquely transmitted illumination.

PMID- 10945584
TI  - Microbial populations on animal hides and beef carcasses at different stages of
      slaughter in plants employing multiple-sequential interventions for
      decontamination.
AB  - Multiple-sequential interventions were applied commercially to reduce beef
      carcass contamination in eight packing plants. The study evaluated microbial
      populations on animal hides and changes in carcass microbial populations at
      various stages in the slaughtering process. Sponge swab samples yielded mean (log
      CFU/100 cm2) total plate counts (TPC), total coliform counts (TCC), and
      Escherichia coli counts (ECC) on the exterior hide in the ranges of 8.2 to 12.5,
      6.0 to 7.9, and 5.5 to 7.5, respectively, while corresponding contamination
      levels on carcass surfaces, after hide removal but before application of any
      decontamination intervention, were in the ranges of 6.1 to 9.1, 3.0 to 6.0, and
      2.6 to 5.3, respectively. Following the slaughtering process and application of
      multiple-sequential decontamination interventions that included steam vacuuming,
      pre-evisceration carcass washing, pre-evisceration organic acid solution rinsing,
      hot water carcass washing, postevisceration final carcass washing, and
      postevisceration organic acid solution rinsing, mean TPC, TCC, and ECC on carcass
      surfaces were 3.8 to 7.1, 1.5 to 3.7, and 1.0 to 3.0, respectively, while
      corresponding populations following a 24 to 36 h chilling period were 2.3 to 5.3,
      0.9 to 1.3, and 0.9, respectively. The results support the concept of using
      sequential decontamination processes in beef packing plants as a means of
      improving the microbiological quality of beef carcasses.

PMID- 10945583
TI  - Modeling the germination kinetics of clostridium botulinum 56A spores as affected
      by temperature, pH, and sodium chloride.
AB  - The germination kinetics of proteolytic Clostridium botulinum 56A spores were
      modeled as a function of temperature (15, 22, 30 degrees C), pH (5.5, 6.0, 6.5),
      and sodium chloride (0.5, 2.0, 4.0%). Germination in brain heart infusion (BHI)
      broth was followed with phase-contrast microscopy. Data collected were used to
      develop the mathematical models. The germination kinetics expressed as cumulated
      fraction of germinated spores over time at each environmental condition were best
      described by an exponential distribution. Quadratic polynomial models were
      developed by regression analysis to describe the exponential parameter (time to
      63% germination) (r2 = 0.982) and the germination extent (r2 = 0.867) as a
      function of temperature, pH, and sodium chloride. Validation experiments in BHI
      broth (pH: 5.75, 6.25; NaCl: 1.0, 3.0%; temperature: 18, 26 degrees C) confirmed
      that the model's predictions were within an acceptable range compared to the
      experimental results and were fail-safe in most cases.

PMID- 10945585
TI  - Acidified sodium chlorite antimicrobial treatment of broiler carcasses.
AB  - An acidified sodium chlorite (ASC) solution was investigated for its
      antimicrobial effects on broiler carcasses processed under conditions similar to
      those used in U.S. commercial poultry facilities. Of particular interest was the
      ability of the ASC solution to reduce natural bioburden in a prechill procedure.
      A number of parameters such as pretreatment washing of carcasses with water (no
      wash versus water wash), ASC concentration (500, 850, and 1,200 ppm), method of
      application (spray versus dip), and method of acid activation (phosphoric acid
      versus citric acid) were explored to evaluate disinfection conditions. ASC dip
      solutions (18.9 liters) were freshly prepared for groups of five prechill
      eviscerated carcasses per treatment (n = 10 carcasses). ASC treatment was shown
      to be an effective method for significantly reducing naturally occurring
      microbial contamination on carcasses. Reductions following immersion dipping were
      demonstrated at all disinfectant concentrations for total aerobes (82.9 to
      90.7%), Escherichia coli (99.4 to 99.6%), and total coliforms (86.1 to 98.5%).
      Additionally, testing showed that ASC solutions maintained stable pH and minimal
      chlorite ion concentration deviations throughout each treatment. The results of
      the parameter evaluations indicated that maximal antimicrobial activity was
      achieved in carcasses that were prewashed and then exposed to a 5-s dip in a
      solution containing phosphoric acid- or citric acid-activated ASC. At 1,200 ppm
      ASC, a mild but transitory whitening of the skin was noted on dipped carcasses.
      The results support the methods currently approved by the U.S. Department of
      Agriculture for the use of ASC solutions as a prechill antimicrobial intervention
      in U.S. poultry processing plants.

PMID- 10945586
TI  - High-pressure processing applied to cooked sausages: bacterial populations during
      chilled storage.
AB  - Vacuum-packaged cooked sausages were pressurized at 500 MPa for 5 or 15 min at
      mild temperature (65 degrees C) and later stored at 2 and 8 degrees C for 18
      weeks. Counts of aerobic mesophiles and psychrotrophs, lactic acid bacteria,
      enterobacteria, Baird-Parker microbiota, and Listeria spp. were determined 1 day
      and 3, 6, 9, 12, 15, and 18 weeks after treatment and compared with those of
      cooked sausages treated at 80 to 85 degrees C for 40 min. Pressurization
      generated reductions of about 4 log CFU/g in psychrotrophs and lactic acid
      bacteria. Enterobacteria and Listeria proved the most pressure sensitive;
      insignificant or no growth was detected throughout the study. Heat treatment
      inactivated psychrotrophs and enterobacteria similarly to pressure treatment.
      Listeria monocytogenes and enterotoxigenic Staphylococcus aureus were not found
      in treated samples. In general, there was no significant difference in counts of
      any bacterial populations either among treatments or between storage
      temperatures. High-pressure processing at mild temperature is an effective
      preservation method that can replace heat pasteurization applied to some cooked
      meat and poultry products after packaging.

PMID- 10945587
TI  - Bactericidal properties of ozone and its potential application as a terminal
      disinfectant.
AB  - The efficacy of ozone as a terminal disinfectant was evaluated under laboratory
      conditions. Different microorganisms of importance to the food industry were
      inoculated onto stainless steel squares and incubated at various temperatures and
      relative humidities for up to 4 h. Survival of microorganisms from these controls
      was compared with identically incubated squares exposed to ozone. Exposure of the
      contaminated surfaces to ozone (2 ppm for 4 h) resulted in a reduction in
      microbial viability that ranged, depending on organism type, from 7.56 to 2.41
      log values. For all the microorganisms tested, this loss in viability was
      significantly greater (P < 0.05) than that observed in the absence of ozone. Gram
      negative bacteria were more sensitive to ozone than gram-positive organisms;
      bacteria were more sensitive than the yeast strain tested. Exposure to ozone (2
      ppm for 4 h) in the presence of ultra-high temperature (UHT) milk resulted in a
      reduction in bacterial viability that ranged from 5.64 to 1.65 log values. In
      most cases, this reduction was significantly less (P < 0.05) than that achieved
      in the absence of organic material, although still significantly greater (P <
      0.05) than that observed in the absence of ozone. The presence of a meat-based
      broth reduced the effectiveness of ozone to a greater extent, although the number
      of surviving gram-negative organisms was still significantly less (P < 0.05) than
      in the absence of ozone. Less than 1 log unit of yeast cells was destroyed when
      exposed to ozone in the presence of UHT milk or meat-based broth. Results of this
      investigation suggest that if applied after adequate cleaning ozone could be used
      as an effective disinfectant.

PMID- 10945588
TI  - An evaluation of methods for the detection of spinal cord in product derived from
      advanced meat recovery systems.
AB  - This study investigated the usefulness of immunohistochemistry, histochemistry,
      and polarization microscopy in documenting the presence of spinal cord in ground
      product produced by advanced meat recovery systems (AMRS). A battery of
      diagnostic stains proved most helpful for definitive documentation of spinal cord
      in the AMRS product. Antibodies to neurofilament and glial fibrillary acidic
      proteins were useful for highlighting the presence of neural tissue in comminuted
      product but when used alone did not definitively differentiate central nervous
      system tissue from peripheral nerve. Polariscopy, trichrome staining, and
      immunostaining for synaptophysin were very useful for differentiating spinal cord
      from peripheral nerve. Spinal cord was found in 2 of 196 AMRS samples when only
      hematoxylin and eosin staining was used. In a later immunohistochemical subset of
      the survey study, spinal cord was found in 7 of 17 AMRS samples. More recently,
      spinal cord tissue has been found in 3 of 26 regulatory samples using hematoxylin
      and eosin stains combined with immunohistochemical techniques.

PMID- 10945589
TI  - Recalls of foods and cosmetics due to microbial contamination reported to the
      U.S. Food and Drug Administration.
AB  - In the U.S., food product recalls serve as an important intervention in stemming
      the consumption of food products contaminated with infectious disease agents. We
      summarize the number and nature of foods and cosmetics recalled as a result of
      microbial contamination reported to the U.S. Food and Drug Administration (FDA)
      for the period 1 October 1993 through 30 September 1998. During this period,
      microbial contamination of food and cosmetic products was the leading cause for
      recalls, accounting for a total of 1,370 recalls (36% of all products recalled).
      Listeria monocytogenes accounted for the greatest number of food products
      recalled because of microbial contamination, whereas Pseudomonas aeruginosa was
      the most common microbe associated with recalls of cosmetic products. Dairy
      products, followed by seafood and pastry items, were the types of products most
      often associated with recalls due to microbial contamination. The FDA was the
      entity most often responsible for detecting microbial contamination of foods and
      cosmetics (33% of all such recalls), followed by state regulatory agencies (24%),
      and manufacturers/retailers (21%). Nineteen percent of recalls were associated
      with at least one reported case of illness. Salmonella was the pathogen most
      often implicated in reports of illness associated with these recalled products.

PMID- 10945590
TI  - Efficacy of disinfectants in killing spores of Alicyclobacillus acidoterrestris
      and performance of media for supporting colony development by survivors.
AB  - Alicyclobacillus has recently emerged as a spoilage microorganism of concern in a
      wide range of pasteurized fruit products. The focus of this study was to
      determine the efficacy of chemical disinfectants in killing Alicyclobacillus
      acidoterrestris spores. Direct plating media were evaluated for their suitability
      to support germination and outgrowth of spores surviving exposure to these
      disinfectants. Significant (P < or = 0.05) reductions of about 2.2, 0.4, and 0.1
      logs in the number of viable A. acidoterrestris spores in a five-strain mixture
      were achieved when spores were suspended in 200 ppm chlorine, 500 ppm acidified
      sodium chlorite, or 0.2% H2O2 solutions, respectively, for 10 min at 23 degrees
      C. When treated with either 1,000 ppm chlorine or 4% H2O2, the number of spores
      was reduced by more than 5 logs. Treatment with 8% trisodium phosphate or 80 ppm
      Tsunami did not significantly reduce numbers of viable spores. Spores of
      individual strains of A. acidoterrestris varied little in resistance to the same
      chemical treatment. K agar (pH 3.7) was judged best for recovering chemically
      treated spores, compared to orange serum agar (pH 5.0) and potato dextrose agar
      (pH 3.5). Experiments were done to determine the effectiveness of chemical
      treatments in killing a mixed-strain inoculum of A. acidoterrestris spores on the
      surface of apples. Treatment with 500 ppm chlorine or 1,200 ppm acidified sodium
      chlorite for 1 min significantly (P < or = 0.05) reduced the number of viable
      spores, but reductions were less than 1 log. Hydrogen peroxide (2%) was
      ineffective in killing spores remaining on the apple skin after treatment.

PMID- 10945591
TI  - Classification of a bacterial isolate, from pozol, exhibiting antimicrobial
      activity against several gram-positive and gram-negative bacteria, yeasts, and
      molds.
AB  - A bacterial isolate, designated CS93, capable of producing a broad-spectrum
      antimicrobial compound(s) effective against gram-positive and gram-negative
      bacteria, yeasts, and molds was isolated from pozol, a fermented maize product.
      This strain was phenotypically similar to another pozol isolate that was
      previously designated as Agrobacterium azotophilium by other investigators. By
      using biochemical, phenotypic, and 16S rRNA sequence analysis, both pozol
      isolates were identified as members of the genus Bacillus, possibly a variant of
      Bacillus subtilis. While the antimicrobial compound(s) was initially produced
      only on a solid medium, parameters were identified for production in broth. The
      compound(s) was heat stable (121 degrees C for 15 min), exhibited activity over a
      wide pH range (pH 3 to pH 11), and was inactivated by pronase E. The
      antimicrobial compound(s) was bactericidal and bacteriolytic against Escherichia
      coli V517, bacteriostatic against Micrococcus luteus, and fungistatic against
      Saccharomyces cerevisiae. The inhibitory compound(s) could possibly serve as a
      food biopreservative.

PMID- 10945592
TI  - Binding of aflatoxin B1 to bifidobacteria in vitro.
AB  - Aflatoxins are mycotoxins that cause health and economic problems when they
      contaminate food and feed. One potential method for reducing human health effects
      due to aflatoxin ingestion is to block uptake via binding by bacteria that either
      make up the normal gut flora or are present in fermented foods in our diet. These
      bacteria would bind aflatoxin and make it unavailable for absorption in the
      intestinal tract. Bifidobacteria comprise a large fraction of the normal gut
      flora, are thought to provide many probiotic effects and are increasingly used in
      fermented dairy products. These qualities targeted bifidobacteria for studies to
      determine if various strains of heat-killed bifidobacteria can bind aflatoxin B1
      (AFB1) in vitro. The AFB1 binding affinities of various strains of
      bifidobacteria, Staphylococcus aureus, and Escherichia coli were quantitated
      utilizing enzyme-linked immunosorbent and [3H]AFB1 binding assays. The bacteria
      analyzed were found to bind significant quantities of AFB1 ranging from 25% to
      nearly 60% of the added toxin. The data also suggest that there are reproducible
      strain differences in AFB1 binding capacity.

PMID- 10945593
TI  - Evaluation of petrifilm series 2000 as a possible rapid method to count coliforms
      in foods.
AB  - This research note is a preliminary comparison between the Petrifilm 2000 method
      and a widely used traditional enumeration method (on violet red bile agar); six
      batches of different foods (egg, frozen green beans, fresh sausage, a bakery
      product, raw minced meat, and raw milk) were studied. The reliability of the
      presumptive counts taken at 10, 12, and 14 h of incubation using this method was
      also verified by comparing the counts with the total confirmed counts at 24 h. In
      all the batches studied, results obtained with Petrifilm 2000 presented a close
      correlation to those obtained using violet red bile agar (r = 0.860) and greater
      sensitivity (93.33% of the samples displayed higher counts on Petrifilm 2000),
      showing that this method is a reliable and efficient alternative. The count taken
      at 10-h incubation is of clear interest as an early indicator of results in
      microbiological food control, since it accounted for 90% of the final count in
      all the batches analyzed. Counts taken at 12 and 14 h bore a greater similarity
      to those taken at 24 h. The Petrifilm 2000 method provides results in less than
      12 h of incubation, making it a possible rapid method that adapts perfectly to
      hazard analysis critical control point system by enabling the microbiological
      quality control of the processing.

PMID- 10945594
TI  - Anisakid larvae in the musculature of the Argentinean hake, Merluccius hubbsi.
AB  - We report the infection levels of third-stage anisakid larva in the muscle of the
      Argentinean hake, Merluccius hubbsi, in relation to fish size and location in the
      musculature. The musculature of 42 hake was separated into hypaxial (ventral) and
      epiaxial (dorsal) parts and surveyed for nematode larvae. Two anisakid species
      were detected: Anisakis sp. (prevalence, 52.4%; mean +/- SD abundance, 1.2 +/-
      1.7) and Pseudoterranova sp. (prevalence, 9.5%; mean +/- SD abundance, 0.2 +/-
      0.7). Since the fish were gutted after capture, the occurrence of anisakids in
      the flesh indicates that the worms had migrated into the muscle before capture.
      The number of Anisakis sp. in muscle was not correlated with fish length or
      weight. Therefore, fish size cannot be used as a predictor of parasite loads in
      the muscle. Only one Anisakis sp. and one Pseudoterranova sp. appeared in the
      epiaxial musculature. The density of Anisakis sp. in the hypaxial muscles was
      significantly higher than that in the epiaxial ones. This suggests that removal
      of the hypaxial musculature can reduce the risk of anisakid-induced allergies and
      gastrointestinal anisakidoses among consumers.

PMID- 10945595
TI  - Microbiological safety of mayonnaise, salad dressings, and sauces produced in the
      United States: a review.
AB  - The literature on the death and survival of foodborne pathogens in commercial
      mayonnaise, dressing, and sauces was reviewed and statistically analyzed with
      emphasis on Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes. The
      absence of reports of foodborne illness associated directly with the consumption
      of commercially prepared acidic dressings and sauces is evidence of their safety.
      Salmonella, E. coli O157:H7, E. coli, L. monocytogenes, Staphylococcus aureus,
      and Yersinia enterocolitica die when inoculated into mayonnaise and dressings.
      Historically, mayonnaise and dressings have been exempt from the acidified food
      regulations and have justly deserved this status due primarily to the toxic
      effect of acetic and to a lesser extent lactic and citric acids. These organic
      acids are inimical to pathogenic bacteria and are effective natural preservatives
      with acetic being the most effective in killing pathogenic bacteria at the pH
      values encountered in these products. Statistical analysis on data reported in
      the literature shows that the most important and significant factor in destroying
      pathogenic bacteria is pH as adjusted with acetic acid followed by the
      concentration of acetic acid in the water phase. The reported highest
      manufacturing target pH for dressings and sauces is 4.4, which is below the 4.75
      pKa of acetic acid and below the reported inhibitory pH of 4.5 for foodborne
      pathogens in the presence of acetic acid. The overall conclusion is that these
      products are very safe. They should remain exempt from the acidified food
      regulations providing adequate research has been done to validate their safety,
      and the predominant acid is acetic and reasonable manufacturing precautions are
      taken.

PMID- 10945596
TI  - Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene
      therapy: role of gap-junctional intercellular communication.
AB  - Antitumor suicide gene therapy is one of the emerging strategies against cancer.
      It consists of the introduction into cancer cells of a gene capable of converting
      a nontoxic prodrug into a cytotoxic drug. Because this therapeutic gene cannot be
      easily introduced into the whole cell population of a tumor, the successful
      eradication of tumors depends on a phenomenon called the "bystander effect," by
      which the introduced gene can affect even cells in which it is not itself
      present. From a therapeutic point of view, it may be crucial to enhance this
      phenomenon through various means to achieve tumor eradication. One such suicide
      gene, the thymidine kinase gene from the herpes simplex virus, in combination
      with the prodrug ganciclovir, has been extensively and successfully used in some
      animal models exhibiting a strong bystander effect. Among the mechanisms involved
      in this phenomenon, gap junctional intercellular communication (GJIC) is directly
      involved in the transfer of the toxic metabolites of ganciclovir, which pass
      directly from herpes simplex virus thymidine kinase-expressing cells to
      surrounding cells that do not express it. Because GJIC appears to be a mediator
      of the bystander effect both in vitro and in vivo, here we review possible
      molecular strategies for enhancing the extent of tumor cell death by increasing
      the intratumoral GJIC capacity.

PMID- 10945597
TI  - Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its
      clinical implication.
AB  - Cyclin B1 is a key molecule for G2-M-phase transition during the cell cycle and
      is overexpressed in various tumor types. However, the expression status of cyclin
      B1 in lung cancer and its clinical significance remain unknown. We used
      immunohistochemistry studies to examine the expression of cyclin B1 in 77 non
      small cell lung cancer specimens from patients with histological stage I disease.
      All of the patients underwent curative surgical treatment. The median length of
      follow-up care is 8.2 years. High-level cyclin B1 expression (a cyclin B1
      labeling index > or =15%) was observed in 17 of the 77 (22%) tumors. Patients
      whose tumors expressed a high level of cyclin B1 had a significantly shorter
      survival time than patients whose tumors expressed a low level of cyclin B1 (P =
      0.02, log-rank test). Interestingly, overexpression of cyclin B1 was more
      frequently observed in tumors with squamous cell histology than in tumors with
      other histological cell types (P = 0.01, Fisher's exact test). A subgroup
      analysis revealed that cyclin B1 overexpression seems to be an adverse prognostic
      factor only in patients with squamous cell carcinoma (SCC) of the lung (P = 0.02,
      log-rank test). Our data indicate that cyclin B1 may be dysregulated in non-small
      cell lung cancer, particularly in the SCC subtype, and that a high level of
      cyclin B1 expression may be a prognostic marker for patients with early-stage SCC
      of the lung.

PMID- 10945598
TI  - Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung
      neuroendocrine tumors in transgenic mice.
AB  - The transcription factor achaete-scute homologue-1 (ASH1) is essential for neural
      differentiation during fetal development and is a cardinal feature of
      neuroendocrine (NE) tumors such as small cell lung cancer. To explore the
      potential of ASH1 to promote NE differentiation and tumorigenesis in the lung, we
      constitutively expressed the factor in nonendocrine airway epithelial cells using
      transgenic mice. Progressive airway hyperplasia and metaplasia developed
      beginning at 3 weeks of life. ASH1 potently enhanced the tumorigenic effect of
      SV40 large T antigen in airway epithelium. These doubly transgenic animals
      developed massive NE lung tumors, implying that ASH1 may cooperate with defects
      in p53, pRb, or related pathways in promoting NE lung carcinogenesis.

PMID- 10945599
TI  - Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth.
AB  - Deficiencies in oxygenation are widespread in solid tumors. The transcription
      factor hypoxia-inducible factor (HIF)-1alpha is an important mediator of the
      hypoxic response of tumor cells and controls the up-regulation of a number of
      factors important for solid tumor expansion, including the angiogenic factor
      vascular endothelial growth factor (VEGF). We have isolated two cell lines
      nullizygous for HIF-1alpha, one from embryos genetically null for HIF-1alpha, and
      the other from embryos carrying loxP-flanked alleles of the gene, which allows
      for cre-mediated excision. The loss of HIF-1alpha negatively affects tumor growth
      in these two sets of H-ras-transformed cell lines, and this negative effect is
      not due to deficient vascularization. Despite differences in VEGF expression,
      vascular density is similar in wild-type and HIF-1alpha-null tumors. The evidence
      from these experiments indicates that hypoxic response via HIF-1alpha is an
      important positive factor in solid tumor growth and that HIF-1alpha affects tumor
      expansion in ways unrelated to its regulation of VEGF expression.

PMID- 10945600
TI  - Down-regulation of p63 is required for epidermal UV-B-induced apoptosis.
AB  - In the epidermis, p53 plays an important role in UV-B protection that led us to
      examine the role, if any, that p63, a p53 homologue highly expressed in the basal
      layer of the epidermis, might play in the epidermal UV-B response. One p63
      isoform, deltaNp63alpha, decreased dramatically in normal keratinocytes or
      newborn epidermis at both the protein and RNA levels after UV-B irradiation. In
      an attempt to further investigate the significance of the UV-B-induced decrease
      of this p63 isoform as well as further delineate the function of p63 in the
      epidermis, we generated transgenic mice that constitutively express
      deltaNp63alpha in the mouse epidermis using the loricrin promoter
      (ML.deltaNp63alpha). The ML.deltaNp63alpha mouse epidermis developed normally,
      with no overt phenotype and an unaltered proliferation rate. When challenged by
      UV-B exposure, the ML.deltaNp63alpha mice exhibited a 40-45% decrease in the
      number of apoptotic cells in the epidermis as compared with nontransgenic
      littermates. These results suggest that aberrant expression of deltaNp63alpha
      altered the UV-B-induced apoptotic pathway in the transgenic epidermis, proving
      that down-regulation of deltaNp63alpha in response to UV-B is important to
      epidermal apoptosis. The forced overexpression of deltaNp63alpha may act via a
      dominant negative effect on the endogenous p53 transcriptional activity required
      for UV-B-induced apoptosis.

PMID- 10945601
TI  - Genetic and epigenetic alterations in normal bladder epithelium in patients with
      metachronous bladder cancer.
AB  - Mechanisms for multifocal bladder carcinogenesis remain unclear. To see whether
      normal mucosa had already acquired genetic or epigenetic changes, we examined
      loss of heterozygosity (LOH) at 10 microsatellite loci and methylation of the
      p16(INK4) CpG island in multiple tumors and pathologically normal mucosa in six
      patients with bladder cancer. Either LOH or methylation was detected in 77% of
      samples of normal epithelium, and LOH detected in samples of normal epithelium
      was also observed in most tumor samples. This result indicated that a population
      of cells in morphologically normal epithelium possessed genetic or epigenetic
      aberrations in common with bladder cancer, which might provide a ground for
      multiple tumorigenesis.

PMID- 10945602
TI  - A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions.
AB  - The best current model of breast cancer evolution suggests that most cancers
      arise from certain premalignant lesions. We have identified a common (34%)
      somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59
      typical hyperplasias, a type of early premalignant breast lesion. The mutation,
      which affects the border of the hinge and hormone binding domains of ER-alpha,
      showed increased sensitivity to estrogen as compared with wild-type ER-alpha in
      stably transfected breast cancer cells, including markedly increased
      proliferation at subphysiological levels of estrogen. The mutated ER-alpha
      exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone,
      which may partially explain its increased estrogen responsiveness. These data
      suggest that this mutation may promote or accelerate the development of cancer
      from premalignant breast lesions.

PMID- 10945603
TI  - Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes.
AB  - Nearly 6000 patients enrolled in four clinical trials of the National Wilms'
      Tumor Study Group during 1969-1995 were followed until death or for a median of
      11.0 years of survival for the onset of renal failure (RF). Thirteen of 22
      patients with Denys-Drash syndrome and 10 of 46 patients with the Wilms' tumor
      aniridia syndrome developed RF. The cumulative risks of RF at 20 years from
      Wilms' tumor diagnosis were 62% and 38%, respectively. Only 21 cases of RF were
      observed among 5358 patients with unilateral disease who did not have
      characteristic congenital genitourinary anomalies, and their risk was <1%.
      Although other explanations cannot be completely excluded, the high rate of RF in
      patients with the aniridia syndrome challenges the view that nephropathy is
      associated uniquely with missense mutations in the WT1 gene. It suggests the
      possibility of a further gradation in the spectrum of phenotypes associated with
      different WT1 mutations. Patients with Wilms' tumor and aniridia or genitourinary
      abnormalities should be followed closely throughout life for signs of nephropathy
      or RF.

PMID- 10945604
TI  - Prostate cancer and other xenografts from cells in peripheral blood of patients.
AB  - Good models for the investigation of human prostate cancer are few. Cells from
      approximately 9.2-21 ml of peripheral blood from patients with metastatic
      prostate cancer or metastatic colon cancer were injected s.c. into nude mice.
      Prostate cancer from 2 of 11 patients and colon cancer from 1 of 3 patients were
      found to be growing as metastases in the lungs of the nude mice. To our
      knowledge, this is the first report of the formation of xenografts from carcinoma
      cells taken directly from the peripheral blood of patients. Expanding circulating
      cancer cells with this approach may have important translational applications
      including: (a) development of models of human cancers; and (b) sampling of
      cancers from specific patients for novel molecular and therapeutic approaches.

PMID- 10945605
TI  - Cancer gene discovery using digital differential display.
AB  - The Cancer Gene Anatomy Project database of the National Cancer Institute has
      thousands of expressed sequences, both known and novel, in the form of expressed
      sequence tags (ESTs). These ESTs, derived from diverse normal and tumor cDNA
      libraries, offer an attractive starting point for cancer gene discovery. Using a
      data-mining tool called Digital Differential Display (DDD) from the Cancer Gene
      Anatomy Project database, ESTs from six different solid tumor types (breast,
      colon, lung, ovary, pancreas, and prostate) were analyzed for differential
      expression. An electronic expression profile and chromosomal map position of
      these hits were generated from the Unigene database. The hits were categorized
      into major classes of genes including ribosomal proteins, enzymes, cell surface
      molecules, secretory proteins, adhesion molecules, and immunoglobulins and were
      found to be differentially expressed in these tumorderived libraries. Genes known
      to be up-regulated in prostate, breast, and pancreatic carcinomas were discovered
      by DDD, demonstrating the utility of this technique. Two hundred known genes and
      500 novel sequences were discovered to be differentially expressed in these
      select tumor-derived libraries. Test genes were validated for expression
      specificity by reverse transcription-PCR, providing a proof of concept for gene
      discovery by DDD. A comprehensive database of hits can be accessed at http://
      www.fau.edu/cmbb/publications/cancergenes. htm. This solid tumor DDD database
      should facilitate target identification for cancer diagnostics and therapeutics.

PMID- 10945606
TI  - Aberrant methylation of the Cyclooxygenase 2 CpG island in colorectal tumors.
AB  - Cyclooxygenases (COXs) are key enzymes that convert arachidonic acid to
      prostaglandins. Overexpression of one of the COX isozymes, COX2, has been shown
      to play an important role in colorectal cancer progression. Recently, however,
      low expression of COX2 has been reported in a subset of colorectal and gastric
      cancers. Aberrant CpG island methylation and associated transcriptional silencing
      are common in colorectal cancer, and we therefore investigated the potential role
      of methylation in the transcriptional silencing of COX2. We examined the
      methylation status of the COX2 5' CpG island in a series of tumor cell lines.
      Among the 33 cell lines examined, dense methylation (>70%) of COX2 was detected
      in 5 cell lines, and partial methylation was detected in 10 cell lines. Detailed
      methylation mapping using bisulfite genomic sequencing revealed that loss of
      expression of COX2 mRNA was closely correlated with methylation of a region
      upstream of exon 1, and expression could be restored by demethylation using the
      DNA methyltransferase inhibitor 5-aza-deoxycytidine. Aberrant methylation of COX2
      was also detected in 12 of 92 (13%) unselected sporadic primary colorectal
      cancers and 7 of 50 (14%) colorectal adenomas. COX2 methylation was strongly
      associated with the presence of the CpG island methylator phenotype (P<0.01),
      inversely related to p53 gene mutation (P<0.01), and unrelated to microsatellite
      instability status. We propose that COX2 expression in colorectal tumors is
      modulated by functional factors that favor high expression and by the CpG island
      methylator phenotype that favors silencing in a subset of cases. These results
      raise the possibility that tumors with COX2 methylation may be less sensitive to
      treatment using specific COX2 inhibitors.

PMID- 10945607
TI  - Novel transcripts of fibroblast growth factor receptor 3 reveal aberrant splicing
      and activation of cryptic splice sequences in colorectal cancer.
AB  - A nested reverse transcription-PCR analysis of FGFR3 from human colorectal
      carcinomas revealed novel mutant transcripts caused by aberrant splicing and
      activation of cryptic splice sequences. Two aberrantly spliced transcripts were
      detected with high frequency in 50% of 36 primary tumors and in 60% of 10 human
      colorectal cancer cell lines. Most transcripts used normal splice sites but
      skipped or included exons 8 and 9. Two mutant transcripts arose from cryptic
      splice donor sites in exon 7 that spliced to exon 10. The predicted translation
      products would exhibit frameshifts and a premature termination codon in exon 10.
      We propose that dysregulation of mRNA splicing frequently generates an aberrant
      FGFR3 transcript that may confer a selectable advantage on clones of cells in
      colorectal tumorigenesis.

PMID- 10945608
TI  - Glutathione S-transferase p elicits protection against H2O2-induced cell death
      via coordinated regulation of stress kinases.
AB  - To elucidate mechanisms underlying glutathione S-transferase p (GSTp)-mediated
      cellular protection against oxidative stress-induced cell death, the effect of
      GSTp on stress signaling pathways was investigated before and after H2O2
      treatment. Under nonstressed conditions, increased expression of GSTp via a tet
      off-inducible GSTp in NIH 3T3 cells increased the phosphorylation of mitogen
      activated protein (MAP) kinase kinase 4, p38, extracellular receptor kinase
      (ERK), and inhibitor of kappa-kinase (IKK), and reduced phosphorylation of MAP
      kinase kinase 7 and Jun NH2-terminal kinase (JNK). Whereas H2O2 treatment of
      cells induced JNK, p38, and IKK activities, in the presence of H2O2 and elevated
      GSTp expression there was an additional increase in ERK, p38, and IKK activities
      and a decrease in JNK activity. GSTp-mediated protection from H2O2-induced death
      was attenuated upon inhibition of p38, nuclear factor KB, or MAP kinase by
      dominant negative or pharmacological inhibitors. Conversely, expression of a
      dominant negative JNK protected cells from H2O2-mediated death. These data
      suggest that the coordinated regulation of stress kinases by GSTp, as reflected
      by increased p38, ERK, and nuclear factor kappaB activities together with
      suppression of JNK signaling, contributes to protection of cells against reactive
      oxygen species-mediated death.

PMID- 10945609
TI  - Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by
      reverse transcription-polymerase chain reaction analysis of IGH-MMSET fusion
      transcripts.
AB  - We and others have recently identified a novel recurring t(4;14)(p16.3; q32)
      translocation in multiple myeloma (MM) that leads to an apparent deregulation of
      the FGFR3 and WHSC1/MMSET genes. Because the presence of IGH-MMSET hybrid
      transcripts has been found in MM cell lines with t(4;14), they may represent a
      specific tumor-associated marker in MM. In this study, we developed a reverse
      transcription-PCR (RTPCR) assay for detecting chimeric transcripts from all of
      the 4p16.3 breakpoints identified thus far, and we used it to investigate a
      representative panel of 53 MM patients and 16 patients with monoclonal gammopathy
      of uncertain significance; in addition, t(4;14) was investigated in all of the MM
      patients by means of two-color fluorescence in situ hybridization. IGH-MMSET
      transcripts were found in 11 of the 53 (20%) MM cases and 1 of 16 (6%) cases of
      monoclonal gammopathy of uncertain significance. There was complete concordance
      between the RT-PCR and fluorescence in situ hybridization analyses of the MM
      cases. The results of this study indicate that RT-PCR is a sensitive and reliable
      method of detecting t(4;14) and suggest that it may be useful for monitoring the
      disease in a significant proportion of patients.

PMID- 10945610
TI  - Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute
      lymphoblastic leukemia.
AB  - Gene targeting studies in mice have shown that the transcription factor Ikaros
      plays an essential role in lymphoid development and as a tumor suppressor in T
      cells, whereas the related gene Aiolos functions as a tumor suppressor in B
      cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and
      Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic
      leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the
      dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL
      patients by reverse transcription-PCR, and the results were confirmed by
      sequencing analysis and immunoblotting. None of the other dominant negative
      isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis.
      Southern blotting analysis with PstI digestion revealed that those patients with
      the dominant negative isoform Ik-6 might have small mutations in the Ikaros
      locus. We did not detect any overexpression of dominant negative isoforms of
      Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role
      in human B-cell malignancies through the dominant negative isoform Ik-6.

PMID- 10945611
TI  - Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse
      mammary carcinoma.
AB  - Photodynamic therapy (PDT) is a promising cancer treatment that induces localized
      tumor destruction via the photochemical generation of cytotoxic singlet oxygen.
      PDT-mediated oxidative stress elicits direct tumor cell damage as well as
      microvascular injury within exposed tumors. Reduction in vascular perfusion
      associated with PDT-mediated microvascular injury produces tumor tissue hypoxia.
      Using a transplantable BA mouse mammary carcinoma, we show that Photofrin
      mediated PDT induced expression of the hypoxia-inducible factor-1alpha (HIF
      1alpha) subunit of the heterodimeric HIF-1 transcription factor and also
      increased protein levels of the HIF-1 target gene, vascular endothelial growth
      factor (VEGF), within treated tumors. HIF-1alpha and VEGF expression were also
      observed following tumor clamping, which was used as a positive control for
      inducing tissue hypoxia. PDT treatment of BA tumor cells grown in culture
      resulted in a small increase in VEGF expression above basal levels, indicating
      that PDT-mediated hypoxia and oxidative stress could both be involved in the
      overexpression of VEGF. Tumor-bearing mice treated with combined antiangiogenic
      therapy (IM862 or EMAP-II) and PDT had improved tumoricidal responses compared
      with individual treatments. We also demonstrated that PDT-induced VEGF expression
      in tumors decreased when either IM862 or EMAP-II was included in the PDT
      treatment protocol. Our results indicate that combination procedures using
      antiangiogenic treatments can improve the therapeutic effectiveness of PDT.

PMID- 10945612
TI  - Invasive properties of murine squamous carcinoma cells: secretion of matrix
      degrading cathepsins is attributable to a deficiency in the mannose 6
      phosphate/insulin-like growth factor II receptor.
AB  - Penetration of basement membrane layers is a hallmark feature of metastatic tumor
      cells. The invasive propensity of murine SCC-VII squamous carcinoma cells is in
      part attributable to the extracellular action of the lysosomal cysteine
      proteinase cathepsin B. Although most noncancerous cells store this enzyme in the
      lysosomes, we found that SCC-VII cells release a large fraction (42%) of their
      newly synthesized procathepsin B into the culture medium. Procathepsins D and L,
      the precursors of other major lysosomal proteinases, are also secreted in
      significant amounts (24 and 75%, respectively). In contrast, normal murine 3T3-L1
      fibroblasts exocytose only minor amounts of their newly synthesized procathepsins
      B (10%), D (<1%), and L (16%). Western blotting analysis revealed that SCC-VII
      cells are deficient in the 300 kDa mannose 6-phosphate/insulin-like growth factor
      II receptor (M6P/IGF2R), a tumor suppressor with a central role in the
      intracellular transport of lysosomal enzymes. Consistent with the absence of
      M6P/IGF2R, SCC-VII cells lack dense lysosomes, with the bulk of intracellular
      acid hydrolases residing in late endosomes/ prelysosomes. On the other hand, the
      synthesis of the M6P recognition marker on lysosomal enzymes is not impaired in
      SCC-VII cells, because [33P]Pi is incorporated into the carbohydrate moieties of
      procathepsins B, D, and L. Furthermore, 69% of the phosphorylated N-linked
      oligosaccharides synthesized by SCC-VII cells carry phosphomonoester groups and
      as such constitute high-affinity ligands for M6P receptors. SCC-VII cells express
      the 46 kDa cation-dependent M6P receptor (MPR46), but intracellular retention of
      procathepsins B, D, and L is not affected by ammonium chloride and chloroquine,
      agents known to perturb the M6P receptor system. Our results indicate that
      failure to express the 300 kDa M6P/IGF2R may enhance the metastatic capacity of
      tumor cells by inducing the secretion of procathepsins B, D, and L.

PMID- 10945613
TI  - Apoptotic response of HL-60 human leukemia cells to the antitumor drug TAS-103.
AB  - TAS-103 is a DNA intercalating indeno-quinoline derivative that stimulates DNA
      cleavage by topoisomerases. This synthetic drug has a broad spectrum of antitumor
      activity against many human solid tumor xenografts and is currently undergoing
      clinical trials. We investigated the induction of apoptosis in human
      promyelocytic leukemia cells treated with TAS-103. The treatment of proliferating
      human leukemia cells for 24 h with various concentrations of the drug induces
      significant variations in the mitochondrial transmembrane potential
      (delta(psi)mt) measured by flow cytometry using the fluorochromes 3,3
      dihexyloxacarbocyanine iodide, Mitotracker Red, and tetrachloro
      tetraethylbenzimidazolcarbocyanine iodide. The collapse of delta(psi)mt is
      accompanied by a marked decrease of the intracellular pH. Cleavage experiments
      with the substrates N-acetyl-Asp-Glu-Val-Asp-pNA, poly(ADP-ribose) polymerase,
      and pro-caspase-3 reveal unambiguously that caspase-3 is a key mediator of the
      apoptotic pathway induced by TAS-103. Caspase-8 is also cleaved, and the bcl-2
      oncoprotein is underexpressed. Drug-induced internucleosomal DNA fragmentation
      and the externalization of phosphatidylserine residues in the outer leaflet of
      the plasma membrane were also characterized. The cell cycle perturbations
      produced by TAS-103 can be connected with the changes in deltapsi(mt). At low
      concentrations (2-25 nM), the drug induces a marked G2 arrest and concomitantly
      provokes an increase in the potential of mitochondrial membranes. In contrast,
      treatment of the HL-60 cells with higher drug concentrations (50 nM to 1 microM)
      triggers massive apoptosis and a collapse of deltaP(mt) that is a signature for
      the opening of the mitochondrial permeability transition pores. The discovery of
      a correlation between the G2 arrest and changes in mitochondrial membrane
      potential provides an important mechanistic insight into the action of TAS-103.

PMID- 10945614
TI  - Nuclear factor kappaB subunits induce epithelial cell growth arrest.
AB  - Nuclear factor kappaB (NF-kappaB) gene-regulatory proteins play important roles
      in inflammation, neoplasia, and programmed cell death. Recently, blockade of NF
      kappaB function has been shown to result in epithelial hyperplasia, suggesting a
      potential role for NF-kappaB in negative growth regulation. We expressed active
      NF-kappaB subunits in normal epithelial cells and found that NF-kappaB profoundly
      inhibits cell cycle progression. This growth inhibition is resistant to mitogenic
      stimuli and is accompanied by other features of irreversible growth arrest. NF
      kappaB-triggered cell cycle arrest is also associated with selective induction of
      the cyclin-dependent kinase inhibitor p21CiP1, with overexpression of p21(Cip1)
      alone inducing findings similar to those seen with NF-kappaB in vitro. An active
      NF-kappaB subunit expressed in the epidermis of p21(CiP1-/- mice, however,
      displays only partial growth-inhibitory effects, suggesting that full NF-kappaB
      growth inhibition is only partially p21(Cip1) dependent in this setting. These
      data indicate that NF-kappaB can trigger cell cycle arrest in epithelial cells in
      association with selective induction of a cell cycle inhibitor.

PMID- 10945615
TI  - Efficacious chemoprevention of primary prostate cancer by flutamide in an
      autochthonous transgenic model.
AB  - Although the etiology of prostate cancer is still not clear, family history,
      hormones, and age are thought to play a role in its initiation and progression.
      There is no cure for the advanced disease. Because prostate cancer initially
      develops as an androgen-dependent tumor, agents with antiandrogen activity have
      become the focus for chemoprevention of this disease. A pilot study was
      undertaken to test the efficacy of flutamide (an antiandrogen) in the transgenic
      adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer. Three
      groups of mice received s.c. implantation of slow-release flutamide pellets: (a)
      low-dose flutamide group (6.6 mg/kg); (b) high-dose flutamide group (33 mg/kg);
      and (c) control placebo group. Efficacy was measured by the absence of palpable
      tumor formation. Prostate tissues/tumors were harvested for evaluation by
      molecular and histology techniques. The low-dose flutamide group did not differ
      significantly from the placebo group, in which palpable tumors initially
      presented at 17 weeks of age, and by 33 weeks, all of the animals developed
      palpable tumors. In the high-dose flutamide group, however, tumors did not appear
      until 24 weeks, a lag of 7 weeks, and by 34 weeks, 42% of the animals were still
      tumor free. The period of time at which 50% of the animals had tumors was 33
      weeks in the high-dose flutamide group, 24.5 weeks in the low-dose flutamide
      group, and 24.5 weeks in the placebo group. The difference between the placebo
      and high-dose flutamide groups was statistically significant (log rank, P =
      0.0036; Wilcoxon's statistical analysis, P = 0.0060). Tumors from high-dose
      flutamide-treated animals were more differentiated and retained much of the
      normal glandular architecture compared with those of the placebo group, whose
      tumors consisted of sheets of poorly differentiated cells. The expression of T
      antigen in the prostate tissues of flutamide-treated animals (at 10 weeks age)
      was lower than that in the comparable placebo-treated group. Flutamide had the
      ability to suppress T antigen-driven carcinogenesis, resulting in a significant
      decrease in the incidence of prostate cancer and an increase in the latency
      period of prostate cancer in TRAMP mice.

PMID- 10945616
TI  - Mutagenesis induced by a single 1,N6-ethenodeoxyadenosine adduct in human cells.
AB  - To study the genotoxic properties of 1,N6-ethenodeoxyadenosine (epsilondA) in
      human cells, a novel site-specific mutagenesis approach was developed, in which a
      single DNA adduct was uniquely placed in either strand of a shuttle plasmid
      vector. The analysis of progeny plasmid derived from the modified strand shows
      that epsilondA, when incorporated into the position of the second A of 5'-CAA
      (codon 61 of the ras gene), is mutagenic in human cells, inducing A-->T, A-->G,
      and A-->C mutations. The efficient induction of A-->T transversions in
      experiments using modified double- and singlestranded DNA substrates supports the
      hypothesis that A:T-->T:A transversions in human and animal tumors induced by
      vinyl compounds reflect misinsertion of dAMP opposite this adduct. Mutagenic
      events were similar when the adduct was incorporated into either the leading or
      the lagging strand. EpsilondA was more mutagenic than 8-oxodeoxyguanosine, which
      induced targeted G-->T transversions in HeLa cells. In Escherichia coli,
      epsilondA did not significantly miscode (<0.27%) even in the presence of induced
      SOS functions.

PMID- 10945617
TI  - Malignant transformation of human fibroblast cell strain MSU-1.1 by N-methyl-N
      nitrosourea: evidence of elimination of p53 by homologous recombination.
AB  - To determine whether N-methyl-N-nitrosourea (MNU) can induce malignant
      transformation of human fibroblasts and whether O6-methylguanine (O6-MeG) is
      involved, two populations of infinite life span cell strain MISU-1.1, differing
      only in level of O6-alkylguanine-DNA alkyltransferase, were treated with MNU and
      assayed for focus formation. MNU caused a dose-dependent increase in the
      frequency of foci in both groups, but the dose required was significantly lower
      in the cells lacking O6-alkylguanine-DNA alkyltransferase, indicating that O6-MeG
      was causally involved. Of 35 independent focus-derived strains assayed for p53
      transactivating abilily, one was heterozygous, and 15 had lost all activity, 1 of
      7 from untreated cells and 14 of 27 from MNU-treated cells. These results
      indicate that loss of p53 is not required for focus formation but may permit
      cells to form foci. Of 35 strains assayed for tumorigenicity, 10 formed malignant
      tumors with a short latency, all 10 lacked wild-type p53. The p53 heterozygous
      strain also formed tumors after a long latency, and the cells from those tumors
      lacked p53 transactivating ability. None of the 19 strains with wild-type p53
      formed tumors. These results indicate that although loss of p53 is not sufficient
      for malignant transformation of MSU-1.1 cells, it may be necessary. Analysis of
      the p53 cDNA from several focus-derived strains lacking p53 activity revealed
      that each contained the same mutation, an A to G transition at codon 215,
      resulting in a change from serine to glycine. Because p53 can be inactivated by
      mutations at any one of a large number of sites, finding the same mutation in
      each strain assayed strongly suggests that the target population included a
      subpopulation of cells with this codon 215 mutation in one allele. Further
      analysis showed that all 15 focus-derived cells strains that lacked p53
      transactivating activity contained two alleles, each with the same codon 215
      mutation, and that the mutant allele in the heterozygous strain also had that
      mutatation. Analysis of the p arm of chromosome 17 of the focus-derived cell
      strains containing the codon 215 mutation revealed seven patterns of loss of
      heterozygosity, evidence of mitotic homologous recombination. Similar analysis of
      a separate series of cell strains, derived from foci induced by cobalt-60,
      revealed four patterns of loss of heterozygosity, only two of which had been
      found with those induced by MNU. These data suggest that homologous mitotic
      recombination, induced by O6-MeG in a subpopulation of cells heterozygous for p53
      mutation, rendered the cells homozygous for loss of p53 activity, that this
      allowed the cells to form foci, and that although loss of p53 is not sufficient
      for malignant transformation, it predisposes cells to acquire the additional
      changes needed for such transformation.

PMID- 10945618
TI  - Decreased ovarian hormones during a soya diet: implications for breast cancer
      prevention.
AB  - Ovarian hormones are biomarkers for breast cancer risk. Soybean consumption may
      be responsible in part for lower levels of ovarian hormones and decreased rates
      of breast cancer in women in Asia compared with Western populations. Soybeans
      contain a significant amount of the isoflavones daidzein and genistein, which are
      weak estrogens. The purpose of this study was to determine whether soya feeding
      decreases circulating levels of ovarian hormones and gonadotropins. Ten healthy,
      regularly cycling women consumed a constant soya-containing diet on a metabolic
      unit, starting on day 2 of a menstrual cycle until day 2 of the next cycle. Blood
      and urine samples were obtained daily for one menstrual cycle before and during
      soy feeding. The diet was calculated to maintain constant body weight, included
      400 kilocalories from a 36-ounce portion of soymilk, and provided 113-207 mg/day
      (154.0+/-8.4 mg/day, mean +/- SE) of total isoflavones. For the group, the soya
      diet provided more carbohydrate and less protein than the home diets. Daily
      consumption of the soya diet reduced circulating levels of 17beta-estradiol by
      25% (P<0.01, Wilcoxon signed rank test, two-tailed) and of progesterone by 45%
      (P<0.0001) compared with levels during the home diet period but had no effect on
      luteinizing hormone or follicle-stimulating hormone. Mean menstrual cycle length
      did not change during the soya diet; a slight decrease in mean luteal cycle
      length was marginally statistically significant (P = 0.06). Urinary excretion of
      isoflavones was 33.8+/-5.3 mg/day (mean +/- SE) and when expressed as percentage
      of intake, varied substantially (21.9+/-3.3% of intake; range, 9.1-36.7%) among
      the subjects. Mean daily serum levels of daidzein and genistein (free and
      conjugated forms) 15 h after soymilk were 2.89+/-0.53 microg/ml and 0.85+/-0.22
      microg/ml, respectively, indicating systemic bioavailability of these substances.
      Secondary analyses by multiple regression showed that decreases in follicular and
      luteal phase 17beta-estradiol levels were positively associated with urinary
      isoflavone excretion, an association affected by age, and were inversely
      associated with decreases in protein intake. Decreases in progesterone levels
      during the soya diet were inversely associated with increases in intakes of
      genistein and were affected by the interaction of the intakes of daidzein with
      energy or with fiber. Consumption of an isoflavone-containing soya diet reduced
      levels of ovarian steroids in normal women over the entire menstrual cycle
      without affecting gonadotropins. This suggests that at least under the conditions
      of this study, soya-induced reductions of circulating ovarian steroids are not
      mediated by gonadotropins. Decreases in ovarian hormones are related to
      isoflavones contained in soy and also to energy intake and other components such
      as protein and fiber but not fat. Our results may explain decreased ovarian
      hormone levels and decreased risk of breast cancer in populations consuming soya
      diets and have implications for reducing breast cancer risk by dietary
      intervention.

PMID- 10945619
TI  - Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive to
      tumor necrosis factor-related apoptosis-inducing ligand.
AB  - Fas (APO-1/CD95) is a transmembrane protein of the tumor necrosis factor
      (TNF)/nerve growth factor receptor superfamily that induces apoptosis in
      susceptible normal and neoplastic cells upon cross-linking by its ligand (FasL).
      TNF-related apoptosis-inducing ligand (TRAIL) is a more recently identified
      member of the TNF superfamily that has been shown to selectively kill neoplastic
      cells by engaging two cell-surface receptors, DR4 and DR5. Two additional TRAIL
      receptors (DcR1 and DcR2) do not transmit an apoptotic signal and have been
      proposed to confer protection from TRAIL-induced apoptosis. We addressed the
      expression of Fas, DR4, and DR5 in thyroid carcinoma cell lines and in 31 thyroid
      carcinoma specimens by Western blot analysis and immunohistochemistry,
      respectively, and tested the sensitivity of thyroid carcinoma cell lines to Fas-
      and TRAIL-induced apoptosis. Fas was found to be expressed in most thyroid
      carcinoma cell lines and tissue specimens. Although cross-linking of Fas did not
      induce apoptosis in thyroid carcinoma cell lines, Fas-mediated apoptosis did
      occur in the presence of the protein synthesis inhibitor cycloheximide,
      suggesting the presence of a short-lived inhibitor of the Fas pathway in these
      cells. Cross-linking of Fas failed to induce recruitment and activation of
      caspase 8, whereas transfection of a constitutively active caspase 8 construct
      effectively killed the SW579 papillary carcinoma cell line, arguing that the
      action of the putative inhibitor occurs upstream of caspase 8. By contrast,
      recombinant TRAIL induced apoptosis in 10 of 12 thyroid carcinoma cell lines
      tested, by activating caspase-10 at the receptor level and triggering a caspase
      mediated apoptotic cascade. Resistance to TRAIL did not correlate with DcR1 or
      DcR2 protein expression and was overcome by protein synthesis inhibition in 50%
      of the resistant cell lines. One medullary carcinoma cell line was resistant to
      Fas-and TRAIL-induced apoptosis, even in the presence of cycloheximide, and to
      transfection of constitutively active caspase-8, suggesting a different
      regulation of the apoptotic pathway. Our observations indicate that TRAIL
      effectively kills carcinomas that originate from the follicular epithelium of the
      thyroid gland, by inducing caspase-mediated apoptosis, and may provide a
      potentially potent therapeutic reagent against thyroid cancer.

PMID- 10945620
TI  - Long-term hydroxytamoxifen treatment of an MCF-7-derived breast cancer cell line
      irreversibly inhibits the expression of estrogenic genes through chromatin
      remodeling.
AB  - Antiestrogen resistance is frequently observed in patients after longterm
      treatment with tamoxifen, a nonsteroidal antiestrogen widely used for endocrine
      therapy of breast cancer. In vitro studies in resistant cells showed that the
      expression of natural estrogen-responsive genes is frequently altered. Using MVLN
      cells, an MCF-7-derived cell model, we previously demonstrated that 4
      hydroxytamoxifen (OHT) treatment irreversibly inactivated an estrogen-regulated
      chimeric luciferase response by a direct effect of the drug and not through a
      cell selection process (E. Badia et al., Cancer Res., 54: 5860-5866, 1994). In
      the present study, we present tamoxifen-resistant but still estrogen-dependent
      clones isolated after long-term treatment of MVLN cells with OHT and show that
      progesterone receptor (PR) expression was irreversibly decreased in some of these
      clones, whereas the PRA:PRB ratio of residual PR remained unchanged. The
      irreversible inactivation of both chimeric luciferase gene and PR gene expression
      was associated with the disappearance of DNase 1-hypersensitive sites. In the
      case of the chimeric gene, at least one of these sites was close to the estrogen
      responsive element. Genomic sequencing analysis of a clone with very low PR
      content did not reveal any methylation on CpG dinucleotides or any mutation in
      the PR gene promoter region. In all of the resistant clones tested and
      independently of their PR content, estrogen receptor expression was only lowered
      by half and remained functional, whereas pS2 expression was not modified. We also
      observed that the residual luciferase activity level (1-2%) of the MVLN clones,
      the luciferase expression of which had been irreversibly inactivated, was raised
      4-fold by trichostatin A treatment. We conclude that long-term OHT treatment may
      modify the chromatin structure and thus could contribute to differentially
      silencing natural target genes.

PMID- 10945621
TI  - Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid:
      association with decreased pRb phosphorylation.
AB  - The incidence of cutaneous malignant melanoma is undergoing a dramatic increase
      in persons with light-color skin in all parts of the world. The prognosis for
      individuals with advanced disease is dismal due to the lack of effective
      treatment options. Thus, there is a need for new approaches to control tumor
      progression. Epidemiological, experimental, and mechanistic data implicate omega
      6 polyunsaturated fatty acids (PUFAs) as stimulators and long-chain omega-3 PUFAs
      as inhibitors of development and progression of a range of human cancers,
      including melanoma. The aim of this study was to assess the mechanisms by which
      docosahexaenoic acid (DHA), an omega-3 PUFA, affects human melanoma cells.
      Exponentially growing melanoma cell lines were exposed in vitro to DHA and then
      assessed for (a) inhibition of cell growth; (b) expression of cyclins and cyclin
      dependent kinase inhibitors in individual cells by flow cytometry and
      immunocytochemistry using specific monoclonal antibodies to cyclin D1, cyclin E,
      p21WAF1/CIP1, or p27(KIP1); and (c) expression of total pRb(T) independent of
      phosphorylation state and hypophosphorylated pRb(P-) in fixed cells by flow
      cytometry and immunocytochemistry using specific monoclonal antibodies to pRb(T)
      or pRb(P-), respectively. After treatment with increasing concentrations of DHA,
      cell growth in a majority of melanoma cell lines (7 of 12) was inhibited, whereas
      in 5 of 12 cell lines, cell growth was minimally affected. Two melanoma cell
      lines were examined in detail, one resistant (SK-Mel-29) and one sensitive (SK
      Mel-110) to the inhibitory activity of DHA. SK-Mel-29 cells were unaffected by
      treatment with up to 2 microg/ml DHA whether grown in the absence or presence of
      1% fetal bovine serum (FBS). No appreciable change was observed in cell growth,
      cell cycle distribution, the status of pRb phosphorylation, cyclin D1 expression,
      or the levels of the cyclin-dependent kinase inhibitors p21 and p27. In contrast,
      SK-Mel-110 cell growth was inhibited by DHA with the cells accumulating either in
      G1 or S phase: 0% in SK-Mel-29 versus 13.3 or 41.2% in SK-Mel-110 in the absence
      or presence of FBS, respectively. In the absence of serum, considerable death
      occurred by apoptosis. In addition, DHA treatment resulted in increasing numbers
      of SK-Mel-110 cells (from 12 to >40%) expressing hypophosphorylated pRb, whereas
      the levels of cyclin D1 and p21 changed little. Expression of p27 in these cells
      increased >2.5 times when grown in the absence of FBS but not in the presence of
      1% FBS. Thus, we show for the first time that DHA inhibits the growth of cultured
      metastatic melanoma cells. Furthermore, growth inhibition correlates with a
      quantitative increase in hypophosphorylated pRb in the representative sensitive
      melanoma cell line SK-Mel-110. Although multiple factors influence pRb
      phosphorylation, it appears that both cyclin D1 and p21 expression do not change
      in the presence of DHA, although p27 was strikingly increased in SK-Mel-110 cells
      in the absence of FBS. The fact that pRb became hypophosphorylated after exposure
      to DHA suggests a cross-talk mechanism between fatty acid metabolism and the pRb
      pathway. Determining the mechanism by which PUFAs can inhibit melanoma growth
      will be an important first step in the rational use of PUFAs as antitumor agents.

PMID- 10945622
TI  - The suppression of human prostate tumor growth in mice by the intratumoral
      injection of a slow-release polymeric paste formulation of paclitaxel.
AB  - Most patients that present in the clinic with prostate cancer have either
      localized or recurrent postradiotherapy therapy tumors that may be amenable to
      injectable treatments using slow-release cytotoxic drugs. The objective of this
      preclinical study was to design an injectable polymeric paste formulation of
      paclitaxel for intratumoral injection into nonmetastatic human prostate tumors
      grown s.c. in mice. Paclitaxel was dissolved (10% w/w) in a blend of a
      biodegradable triblock copolymer of a random copolymer of D,L-lactide and epsilon
      caprolactone (PLC) with poly(ethyleneglycol) [PEG; PLC-PEG-PLC] blended with
      methoxypoly(ethylene glycol) in a 40:60 ratio. Human prostate LNCaP tumors grown
      s.c. in castrated athymic male mice were injected with 100 microl of this paste
      at room temperature. Changes in tumor progression were assessed using both serum
      prostate-specific antigen (PSA) levels and tumor size. Paclitaxel inhibited LNCaP
      cell growth in vitro in a concentration-dependent fashion with an IC50 of 1 nM.
      Apoptosis was documented using DNA fragmentation analysis. The paste formulation
      solidified over a period of 1 h both in vivo and in aqueous media at 37 degrees C
      as the methoxypoly(ethylene glycol) component partitioned out of the insoluble
      PLC-PEG-PLC/paclitaxel matrix. The semisolid implant released drug at a rate of
      about 100 microg/day in vitro. In control mice treated with paste without
      paclitaxel, serum PSA levels increased from 2-8 ng/ml (mean, 4.3+/-2 ng/ml) to 60
      292 ng/ml (mean, 181+/-88 ng/ml), and tumor volume increased from 30 to 1000 mm3.
      In mice treated with a single 100-microl injection 3 weeks after castration
      (early-phase treatment group), tumors decreased in volume from a mean of 43+/-19
      mm3 to nonpalpable, and PSA levels decreased from a mean of 22+/-8 to 2+/-1 ng/ml
      by 8 weeks after castration. In mice treated 5 weeks after castration (androgen
      independent tumors; late-phase treatment group), tumors decreased in volume from
      a mean of 233+/-136 mm3 to nonpalpable, and serum PSA decreased from 24+/-8 to
      9+/-4 ng/ml. Observed side effects of the treatment were limited to minor
      ulceration at the needle injection site in paclitaxel-treated mice only. The
      controlled-release formulation can be injected via 22-gauge needles and is
      effective in inhibiting LNCaP tumor growth and PSA levels in mice bearing
      multiple nonmetastatic tumors. Paclitaxel may be an effective therapy for
      patients with localized tumors recurring after radiotherapy and for some patients
      with localized tumors who are not candidates for radical treatment.

PMID- 10945623
TI  - SU6668 is a potent antiangiogenic and antitumor agent that induces regression of
      established tumors.
AB  - Vascular endothelial growth factor, fibroblast growth factor (FGF), and platelet
      derived growth factor (PDGF) and their cognate receptor tyrosine kinases are
      strongly implicated in angiogenesis associated with solid tumors. Using rational
      drug design coupled with traditional screening technologies, we have discovered
      SU6668, a novel inhibitor of these receptors. Biochemical kinetic studies using
      isolated Flk-1, FGF receptor 1, and PDGF receptor beta kinases revealed that
      SU6668 has competitive inhibitory properties with respect to ATP.
      Cocrystallographic studies of SU6668 in the catalytic domain of FGF receptor 1
      substantiated the adenine mimetic properties of its oxindole core. Molecular
      modeling of SU6668 in the ATP binding pockets of the FIk-1/KDR and PDGF receptor
      kinases provided insight to explain the relative potency and selectivity of
      SU6668 for these receptors. In cellular systems, SU6668 inhibited receptor
      tyrosine phosphorylation and mitogenesis after stimulation of cells by
      appropriate ligands. Oral or i.p. administration of SU6668 in athymic mice
      resulted in significant growth inhibition of a diverse panel of human tumor
      xenografts of glioma, melanoma, lung, colon, ovarian, and epidermoid origin.
      Furthermore, intravital multifluorescence videomicroscopy of C6 glioma xenografts
      in the dorsal skinfold chamber model revealed that SU6668 treatment suppressed
      tumor angiogenesis. Finally, SU6668 treatment induced striking regression of
      large established human tumor xenografts. Investigations of SU6668 activity in
      cancer patients are ongoing in Phase I clinical trials.

PMID- 10945625
TI  - The role of the E1B 55 kDa gene product in oncolytic adenoviral vectors
      expressing herpes simplex virus-tk: assessment of antitumor efficacy and
      toxicity.
AB  - In this study, we evaluated three herpes simplex virus-1 thymidine kinase (HSV
      tk) carrying replication-competent adenoviral vectors with and without the Ad5
      E1B 55 kDa gene to assess whether this gene product has an influence on their
      antitumor efficacy, replication kinetics, and potential hepatotoxicity.
      Furthermore, we assessed the efficacy of these vectors in combination with
      ganciclovir (GCV). When compared with wild-type adenovirus, the recombinant
      vectors, in particular the E1B 55 kDa-deleted vector Ad.TK(RC)(II), generated a
      more efficiently cytopathic effect in proliferating cells, independently of their
      p53 phenotype. In a s.c. A549 lung cancer xenograft model, the cytoreductive
      effect of Ad.TK(RC)(II) was enhanced when followed by GCV treatment. In contrast,
      the efficacy of both E1B 55 kDa-positive vectors could not be further improved by
      GCV. In an i.p. MDAH 2774 ovarian cancer xenograft tumor model, the survival of
      animals treated with a prototypical replication-deficient adenovirus expressing
      HSV-tk (Ad.TK) was improved compared to controls when followed by GCV. In
      contrast, the cytoreductive efficacy of the replication-competent vectors was
      diminished when combined with the virostatic GCV. However, the antitumor effect
      of all replication-competent vectors was superior to combination chemotherapy
      with paclitaxel and carboplatin. In both tumor models, the oncolytic effect of
      the E1B 55 kDa-positive vectors was greater than that of Ad.TK(RC)(II). In an
      attempt to assess the toxicity of these vectors in a nonpermissive host, the
      viruses were administered systemically to immunocompetent and immunodeficient
      mice. Greater hepatotoxicity was seen with i.v. administration of the replication
      competent viruses than with Ad.TK and in immunocompetent hosts, suggesting
      involvement of the immune system in the induction of tissue damage. The E1B 55
      kDa gene had no significant influence on the liver toxicity of the vectors in
      this system. At therapeutic doses, intratumoral or i.p. injection of all vectors
      was well tolerated. Importantly, these replication-competent HSV-tk-expressing
      vectors were highly susceptible to GCV, representing an effective fail-safe
      mechanism to abolish viral replication in a clinical setting. Controllable
      intratumoral viral replication holds promise as a new treatment modality for
      cancer.

PMID- 10945624
TI  - Monitoring the expression profiles of doxorubicin-induced and doxorubicin
      resistant cancer cells by cDNA microarray.
AB  - Drug resistance in cancer is a major obstacle to successful chemotherapy. Cancer
      cells exposed to antitumor drugs may be directly induced to express a subset of
      genes that could confer resistance, thus allowing some cells to escape killing
      and form the relapsed resistant tumor. Alternatively, some cancer cells may be
      expressing an array of genes that could confer intrinsic resistance, and exposure
      to cytotoxic drugs select for the survival of these cells that form the relapsed
      tumor. We have used cDNA microarray to monitor the expression profiles of MCF-7
      cells that are either transiently treated with doxorubicin or selected for
      resistance to doxorubicin. Our results showed that transient treatment with
      doxorubicin altered the expression of a diverse group of genes in a time
      dependent manner. A subset of the induced genes was also found to be
      constitutively overexpressed in cells selected for resistance to doxorubicin.
      This distinct set of overlapping genes may represent the signature profile of
      doxorubicin-induced gene expression and resistance in cancer cells. Our studies
      demonstrate the feasibility of obtaining potential molecular profile or
      fingerprint of anticancer drugs in cancer cells by cDNA microarray, which might
      yield further insights into the mechanisms of drug resistance and suggest
      alternative methods of treatment.

PMID- 10945626
TI  - One-step single-chain Fv recombinant antibody-based purification of gp96 for
      vaccine development.
AB  - Heat shock proteins such as gp96 (grp94) isolated from tumor or infected cells
      are able to induce specific cytotoxic T-cell responses and protective immunity.
      To facilitate rapid and efficient isolation, we generated gp96-specific
      recombinant single-chain Fv (scFv) antibodies from a semisynthetic phage display
      library. When immobilized on Sepharose beads, these antibodies allow a high
      yield, one-step purification of native gp96 molecules from both mouse and human
      tumor cell lysates. gp96 molecules eluted from these affinity columns under mild
      conditions are still capable of generating antigen-specific CTL responses in
      mice. Thus, scFv-purified gp96 is still associated with peptides; however, in
      contrast to conventionally purified gp96, scFv-isolated gp96 is free of
      contaminating material such as mitogenic concanavalin A and proteolytic
      cathepsins. With the help of these high-yield antibody columns, it is now
      possible to rapidly isolate immunogenic gp96-peptide complexes from small amounts
      of tumor material to a purity that allows their use in cancer immunotherapy
      protocols.

PMID- 10945627
TI  - Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human
      NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug
      therapy.
AB  - A novel prodrug activation system, endogenous in human tumor cells, is described.
      A latent enzyme-prodrug system is switched on by a simple synthetic, small
      molecule co-substrate. This ternary system is inactive if any one of the
      components is absent. CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is an
      antitumor prodrug that is activated in certain rat tumors via its 4-hydroxylamine
      derivative to a potent bifunctional alkylating agent. However, human tumor cells
      are resistant to CB 1954 because they are unable to catalyze this bioactivation
      efficiently. A human enzyme has been discovered that can activate CB 1954, and it
      has been shown to be commonly present in human tumor cells. The enzyme is NQO2
      [NAD(P)H quinone oxidoreductase 2], but its activity is normally latent, and a
      nonbiogenic co-substrate such as NRH [nicotinamide riboside (reduced)] is
      required for enzymatic activity. There is a very large (100-3000-fold) increase
      in CB 1954 cytotoxicity toward either NQO2-transfected rodent or nontransfected
      human tumor cell lines in the presence of NRH. Other reduced pyridinium compounds
      can also act as co-substrates for NQO2. Thus, the simplest quaternary salt of
      nicotinamide, 1-methyl-3-carboxamidopyridinium iodide, was a co-substrate for
      NQO2 when reduced to the corresponding 1,4-dihydropyridine derivative. Increased
      chain length and/or alkyl load at the 1-position of the dihydropyridine ring
      improved specific activity, and compounds more active than NRH were found.
      However, little activity was seen with either the 1-benzyl or 1-(2-phenylethyl)
      derivatives. A negatively charged substituent at the 3-position of the reduced
      pyridine ring also negated the ability of these compounds to act as cosubstrates
      for NQO2. In particular, 1-carbamoylmethyl-3-carbamoyl-1,4dihydropyridine was
      shown to be a co-substrate for NQO2 with greater stability than NRH, with the
      ability to enter cells and potentiate the cytotoxicity of CB 1954. Furthermore,
      this agent is synthetically accessible and suitable for further pharmaceutical
      development. NQO2 activity appears to be related to expression of NQO1 (DT
      diaphorase), an enzyme that is known to have a favorable distribution toward
      certain human cancers. NQO2 is a novel target for prodrug therapy and has a
      unique activation mechanism that relies on a synthetic co-substrate to activate
      an apparently latent enzyme. Our findings may reopen the use of CB 1954 for the
      direct therapy of human malignant disease.

PMID- 10945628
TI  - Role of poly(ADP-ribosyl)ation in the killing of chronic lymphocytic leukemia
      cells by purine analogues.
AB  - Although the nucleoside analogues fludarabine and chlorodeoxyadenosine have
      become important therapeutic agents in chronic lymphocytic leukemia (CLL), their
      effectiveness is limited by drug resistance. Because such resistance is likely to
      result from impaired drug-induced apoptosis, it is clearly important to
      understand the mechanisms involved in this process. Whereas p53 can contribute to
      the nucleoside-induced killing of CLL cells, recent work from this laboratory and
      elsewhere has shown that such killing can also occur by p53-independent
      mechanisms. Because poly(ADP-ribose) polymerase (PARP)-mediated NAD+/ATP
      depletion has been implicated in the nucleoside-induced killing of normal resting
      lymphocytes, we postulated that this mechanism might account for the p53
      independent component of nucleoside cytotoxicity in CLL. To address this
      question, we used 3-aminobenzamide (3AB) at a concentration (200 microM) known to
      produce selective inhibition of poly(ADP-ribosyl)ation in intact cells and
      examined nucleoside-induced killing using a number of different end points (cell
      membrane disruption, cell shrinkage, mitochondrial depolarization, exposure of
      phosphatidyl serine, morphological changes, DNA fragmentation, and PARP-1
      cleavage). In 27 of the 30 cases of CLL examined, 3AB delayed nucleoside-induced
      cell membrane disruption without inhibiting other manifestations of cytotoxicity.
      This indicates that PARP activity, rather than contributing to the induction of
      cell killing, was accelerating cell membrane disruption during the late stages of
      apoptosis. This novel observation has important implications for previous studies
      of PARP-mediated cytotoxicity. However, in cells from one CLL patient, 3AB
      inhibited all manifestations of nucleoside cytotoxicity; this was the only case
      in the study known to have a p53 gene defect affecting both alleles. This
      indicates that PARP activity can occasionally be central to nucleoside-induced
      killing and that such PARP-mediated killing is p53 independent.

PMID- 10945629
TI  - Regulation of targeted chemotherapy with cytotoxic lutenizing hormone-releasing
      hormone analogue by epidermal growth factor.
AB  - Targeting chemotherapy selectively to cancers can reduce the toxic side effects.
      AN-152, a conjugate of doxorubicin and [D-Lys6]-luteinizing hormone-releasing
      hormone (LH-RH), is more potent against LH-RH receptor-bearing cancers and
      produces less peripheral toxicity than doxorubicin. Many cancers, e.g., 50% of
      breast cancers, but few normal tissues express these receptors, providing a
      selective target for this cytotoxic conjugate. In this study, the effectiveness
      of AN-152 was heightened by receptor up-regulation. The cytotoxic effect of AN
      152 can be regulated by the number of active LH-RH receptors on cancer cells. LH
      RH receptor-positive (MCF-7) and -negative (UCI-107) cancer cells were treated
      with epidermal growth factor (EGF) or the somatostatin analogue, RC-160. EGF and
      RC-160 have been shown previously to regulate LH-RH receptors through
      phosphorylation. The effect of receptor regulation, by hormone exposure, on the
      cytotoxicity of AN-152 and doxorubicin and on the cellular uptake of AN-152, [D
      Lys6]LH-RH, or doxorubicin was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay and by two-photon laser scanning microscopy.
      The results demonstrated that the cellular entry of the conjugate was: (a)
      specific for cancers with LH-RH receptors; (b) up-regulated by EGF; (c) down
      regulated by RC-160; and (d) the cytotoxicity of the AN-152 paralleled the
      efficiency of entry. This study illustrates the potential use of receptor
      regulation for increasing the efficacy of chemotherapeutic approaches that are
      directed to cell surface receptors.

PMID- 10945630
TI  - Experimental photoimmunotherapy of hepatic metastases of colorectal cancer with a
      17.1A chlorin(e6) immunoconjugate.
AB  - Photoimmunotherapy (using a monoclonal antibody-targeted photosensitizer and red
      light) may be a strategy to overcome the limitations inherent in photodynamic
      therapy of liver tumors. The aims of this study were (a) to test the efficacy of
      selective treatment of hepatic metastases of colorectal cancer in an orthotopic
      murine xenograft using the murine monoclonal antibody 17.1A conjugated to the
      photosensitizer chlorin(e6), and (b) to compare the tumor response after the same
      light dose was delivered at two different fluence rates. Based on previous
      biodistribution studies that had shown that the photoimmunoconjugate with a
      polyanionic charge had both a higher absolute tumor chlorin(e6) content and a
      greater tumor:normal liver ratio than those obtained with a photoimmunoconjugate
      bearing a polycationic charge, mice were treated 3 h after i.v. injection of the
      polyanionic 17.1A chlorin(e6) conjugate or unconjugated photosensitizer. Red
      light was delivered into the liver tumor by an interstitial fiber, and tumor
      response end points were total tumor weight in the short term and survival in the
      long term. There was a highly significant reduction (<20% of controls; P =
      0.0035) in the weight of the tumors in the mice treated with photoimmunotherapy,
      and the median survival increased from 62.5 to 102 days (P = 0.015). Photodynamic
      therapy with free chlorin(e6) produced a smaller decrease in tumor weight and a
      smaller extension of survival, neither of which were statistically significant. A
      comparison of photoimmunotherapy with 10 J of light delivered at 30 or 300 mW
      showed that the higher fluence rate prolonged survival significantly more than
      the lower fluence rate. This may have been because the high fluence rate gave a
      contribution of laser-induced hyperthermia to the photodamage. Correlation
      studies showed that the amount of normal liver remaining at necropsy correlated
      best with survival. Photoimmunotherapy shows efficacy in destroying liver tumors,
      and future studies should maximize selectivity to minimize the destruction of
      normal liver.

PMID- 10945631
TI  - Activation of CPT-11 in mice: identification and analysis of a highly effective
      plasma esterase.
AB  - The camptothecin prodrug CPT-11 (irinotecan, 7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxycamptothecin) is converted by esterases to yield the potent
      topoisomerase I poison SN-38 (7-ethyl-10-hydroxycamptothecin). Recently, a mouse
      strain (Es1(e)) has been identified that demonstrates reduced plasma esterase
      activity, and we have monitored the ability of plasma from these mice to
      metabolize CPT-11. Total plasma esterase activity was reduced 3-fold in
      Esl(e)mice in comparison to control mice, and this resulted in a 200-fold
      reduction in SN-38 production after incubation with CPT-11 in vitro. In addition,
      pharmacokinetic studies of CPT-11 and SN-38 in these animals demonstrated
      approximately 5-fold less conversion to SN-38. However, extracts derived from
      tissues from Es1(e) animals revealed total esterase activities similar to those
      of control mice, and these extracts metabolized CPT-11 with equal efficiency.
      Northern analysis of RNA isolated from organs indicated that the liver was the
      primary source of Es-1 gene expression and that very low levels of Es-1 RNA were
      present in Es1(e) mice. These results suggest that the reduced levels of Es-1
      esterase present in Es1(e) mice are due to down-regulation of gene transcription,
      and that this plasma esterase is responsible for the majority of CPT-11
      metabolism in mice.

PMID- 10945632
TI  - Adoptive immunotherapy by avidin-driven cytotoxic T lymphocyte-tumor bridging.
AB  - We have shown previously that T cells, tagged with biotinylated anti-CD3 antibody
      fragments, can exert avidin-dependent cytolytic activity on suitably biotinylated
      tumor cells in vitro. In this study, we demonstrate that avidin-driven CTL-tumor
      bridging in vivo leads to growth inhibition of murine tumors WEHI-164
      fibrosarcoma and RMA lymphoma. The biodistribution of biotin-tagged 111In-labeled
      T cells demonstrated a selective avidin-dependent and time-dependent accumulation
      of radioactivity at tumor sites. The specificity of lymphocyte tumor localization
      was demonstrated by the concurrent time-dependent decrease of radioactivity in
      the blood and in all other organs. Furthermore, we documented a therapeutic
      effect of the adoptively transferred T cells, i.e., a significant delay of tumor
      growth at early stages. All of the experiments included a control group of mice,
      which received all of the reagents, except avidin. These avidin-minus mice showed
      no specific localization and no delay in tumor growth, indicating that avidin
      bridging was essential for T-cell activity at tumor sites.

PMID- 10945633
TI  - hMLH1 and hMSH2 expression correlates with allelic imbalance on chromosome 3p in
      non-small cell lung carcinomas.
AB  - DNA mismatch repair genes have been implicated in the pathogenesis and
      predisposition of certain malignancies through a mutator phenotype. In this
      study, we investigated, in 150 non-small cell lung carcinomas, the expression
      levels of hMLH1 and hMSH2 proteins in relation to loss of heterozygosity on
      chromosomes 3p and 2p, the mutational status of these genes' promoters and the
      hot spot exons. We have demonstrated that 88 of 150 (58.6%) tumor specimens had
      reduced expression levels of the hMLH1 protein, whereas 85 of 147 (57.8%)
      specimens had reduced expression levels of the hMSH2 protein. Reduced expression
      levels of both proteins were observed in 51 of 150 (34%) specimens. In
      adenocarcinomas, the reduction of hMSH2 expression was more frequently observed
      than that of hMLH1 (P<0.003), whereas in squamous cell carcinoma of the lung
      hMLH1 expression was more frequently reduced than hMSH2 (P<0.006). Reduced
      expression of hMLH1correlated with allelic imbalance on loci D3S1289 (P<0.0002)
      and D2S391 (P<0.05). It is of note that an inverse correlation was found between
      hMSH2 reduced expression and loss of heterozygosity at locus D3S1300 (P = 0.016).
      In addition, hMLH1 reduced expression was more frequently associated with heavy
      smokers, assessed by daily tobacco uptake (P = 0.018) and total smoking exposure
      (pack-years; P<0.05). In addition, a correlation between hMLH1 reduced expression
      and nodal metastasis in squamous cell carcinoma of the lung was observed (P =
      0.015). No mutations were identified in the promoters or exons examined in these
      two genes. These findings indicate that hMLH1 and hMSH2 gene inactivation is a
      common event in the development of non-small cell lung carcinoma and allelic loss
      seems to be a major genetic event involved in hMLH1 silencing. In addition, we
      propose that a putative negative regulator of hMSH2 gene may be located at the
      locus 3p14.

PMID- 10945634
TI  - Stabilization of the Ras oncoprotein by the insulin-like growth factor 1 receptor
      during anchorage-independent growth.
AB  - R- cells are 3T3 cells derived from mouse embryos with a targeted disruption of
      the type 1 insulin-like growth factor receptor (IGF-IR) genes. R- cells are
      refractory to transformation by a variety of viral and cellular oncogenes,
      including an activated Ras. R- cells stably transfected with an activated Ha-Ras
      (R-Ras cells) fail to form colonies in soft agar. An IGF-IR truncated at residue
      1245 cannot transform R- cells, even when strongly overexpressed. However, the
      combination of the truncated IGF-IR and an activated Ras induces transformation
      of R- cells. We show here that the Ras oncoprotein is rapidly degraded when R-Ras
      cells are grown under anchorage-independent conditions and that signaling from
      the truncated IGF-IR stabilizes Ras. In monolayer cultures, Ras levels remain
      constant regardless of the presence or absence of IGF-IR signaling. These results
      directly explain why Ras cannot transform mouse embryo fibroblasts devoid of IGF
      IR. They also suggest a more generalized, alternative mechanism for
      transformation by Ras and, implicitly, another possible way for targeting Ras in
      tumor cells.

PMID- 10945635
TI  - Nuclear and mitochondrial genome instability in human breast cancer.
AB  - We analyzed 40 pairs of breast normal/cancer tissues for the presence of
      mitochondrial (mt) genome instability and nuclear MSI in tumor cells. As mt,
      markers we used a (CA)n mt microsatellite (MS) starting at the 514-bp position of
      the D loop region and 4 informative MnlI sites located between the 16,108- and
      16,420-bp positions of the D loop region. Nuclear microsatallite instability
      (MSI) was tested with 8 (CA)n MS, syntenic for the 13q chromosome arm. Moreover,
      we tested the spontaneous frequency of mtMSI and mt-MnlI mutations in 459
      mother/descendant events. Mutations of mt-MnlI sites were found in 19 of 40
      (47.5%) breast tumors, representing a 216-fold increase over the spontaneous rate
      in the female germline. Instability of the mtMS occurred in 17 of 40 (42.5%)
      breast cancers, which implies a 16-fold increase over the rate of spontaneous
      mutations. Nuclear MSI was found in 20 of 40 (50%) cases. In 15 of these cases
      the MSI was restricted to one locus, whereas in 5 instances the change of alleles
      was detected in 2 or 3 loci. Analysis of the correlation between mt and nuclear
      mutations showed no significant associations, suggesting that different systems
      are responsible for mt and nuclear genome instability in tumor cells. We propose
      that the two main mechanisms producing mtRFLP and mtMSI are damage by free
      radicals and error repair by the polymerase gamma, the first mechanism being a
      major cause of MnlI mutations and a secondary cause of mtMSI.

PMID- 10945636
TI  - Increased resistance to anticancer therapy of mouse cells lacking the poly(ADP
      ribose) polymerase attributable to up-regulation of the multidrug resistance gene
      product P-glycoprotein.
AB  - Mouse embryo fibroblasts lacking poly(ADP-ribose) polymerase (PARP)-1 express a
      barely detectable level of wild-type (wt) p53 protein. Doxorubicin at
      concentrations activating wt p53 in normal mouse embryo fibroblasts failed to
      induce it in mutant cells. wt p53 was only activated in response to a 10-fold
      higher doxorubicin dose. Treatment with higher doxorubicin concentrations was
      cytotoxic for normal but not for PARP-1 -/- cells. The latter was also resistant
      to other anticancer agents. The increased resistance of mutant cells to drugs
      resembled a unique phenomenon known as multidrug resistance (MDR). Interestingly,
      the MDR gene product P-glycoprotein was clearly up-regulated in PARP-1-deficient
      cells as compared with normal counterparts. Pretreatment with verapamil reversed
      the MDR phenotype.

PMID- 10945637
TI  - Increased expression of fibroblast growth factor 6 in human prostatic
      intraepithelial neoplasia and prostate cancer.
AB  - Fibroblast growth factors (FGFs) are known to play an important role in the
      growth of normal prostatic epithelial cells. In addition to their effects on
      proliferation, FGFs can promote cell motility, increase tumor angiogenesis, and
      inhibit apoptosis, all of which play an important role in tumor progression. To
      determine whether FGFs are overexpressed in human prostate cancers, we analyzed
      26 prostate cancer RNAs by reverse transcription-PCR for expression of FGF3,
      FGF4, and FGF6, which cannot be detected in normal prostate tissue by this
      technique. Fourteen of 26 prostate cancers expressed FGF6 mRNA. No expression of
      FGF3 or FGF4 was detected. An ELISA of tissue extracts of normal prostate, high
      grade prostatic intraepithelial neoplasia (PIN), and prostate cancer for FGF6
      showed that this growth factor was undetectable in normal prostate but was
      present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate
      cancers. Immunohistochemical analysis with anti-FGF6 antibody revealed weak
      staining of prostatic basal cells in normal prostate that was markedly elevated
      in PIN. In the prostate cancers, the majority of cases revealed expression of
      FGF6 by the prostate cancer cells themselves. In two cases, expression was
      present in prostatic stromal cells. Exogenous FGF6 was able to stimulate
      proliferation of primary prostatic epithelial and stromal cells, immortalized
      prostatic epithelial cells, and prostate cancer cell lines in tissue culture. FGF
      receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the
      human prostate in vivo and in all of the cultured cell lines. Thus, FGF6 is
      increased in PIN and prostate cancer and can promote the proliferation of the
      transformed prostatic epithelial cells via paracrine and autocrine mechanisms.

PMID- 10945638
TI  - Oncotic pressure in solid tumors is elevated.
AB  - Oncotic and hydrostatic pressure differences control the movement of fluid and
      large molecules across the microvascular wall of normal and tumor tissues. Recent
      studies have shown that the interstitial fluid pressure in tumors is elevated and
      is approximately equal to the microvascular pressure. Whereas oncotic pressure in
      blood plasma of various species is known, no data are available on the oncotic
      pressure in the interstitial space of tumors. We hypothesize that because of the
      leaky nature of tumor vessels, oncotic pressure in tumor interstitium should be
      close to that in plasma. To this end, we first developed a chronic wick method
      for the direct measurement of oncotic pressures in the interstitial fluid of
      tumors grown in mice. We found interstitial oncotic pressures in four human tumor
      xenografts to be higher than in s.c. tissue and comparable to that in plasma
      [rhabdomyosarcoma (RD), 24.2+/-4.7; squamous cell carcinoma (FaDu), 19.9+/-1.9;
      small cell lung carcinoma (54A), 21.1+/-2.8; colon adenocarcinoma (LIS174T),
      16.7+/-3.0 mm Hg; s.c. tissue, 8.2+/-2.3; plasma, 20.0+/-1.6 mm Hg]. These
      results support our hypothesis that the oncotic pressure difference across the
      tumor microvascular wall is low. The high oncotic pressure in tumors is
      consistent with the elevated interstitial fluid pressure, and it contributes to
      the suboptimal delivery of large therapeutic agents to neoplastic cells.

PMID- 10945639
TI  - The oncogenic properties of the HMG-I gene family.
AB  - The HMG-I gene family encodes high mobility group proteins originally identified
      as nonhistone chromosomal binding proteins. HMG-I and -Y proteins are
      alternatively spliced products of the same mRNA; HMG-C is encoded by a separate
      gene. The HMG-I proteins function as architectural chromatin-binding proteins
      that bind to the narrow groove of AT-rich regions in double-stranded DNA. Recent
      studies indicate an important role for HMG-I proteins in regulating gene
      expression. Moreover, increased expression of the HMG-I, -Y, and -C proteins
      correlates with cellular proliferation and neoplastic transformation in several
      cell types and human cancers. Previous work from our laboratory has shown that
      HMG-I is a direct c-Myc target gene that is involved in Myc-mediated neoplastic
      transformation. In this report, we show that increased expression of HMG-Y or -C
      leads to transformation with anchorage-independent cell growth in two
      experimental cell lines in a manner similar to that of HMG-I or c-Myc. Moreover,
      Rat la cells overexpressing HMG-Y or -C form tumors in nude mice analogous to Rat
      1a cells overexpressing HMG-I or c-Myc. Distant metastases developed in animals
      injected with cells overexpressing HMG-I or -C. Our findings suggest that the HMG
      I gene family is involved in neoplastic transformation and may represent a new
      family of oncogenes important in the pathogenesis of several human cancers.

PMID- 10945640
TI  - Cytokines prevent dexamethasone-induced apoptosis via the activation of mitogen
      activated protein kinase and phosphatidylinositol 3-kinase pathways in a new
      multiple myeloma cell line.
AB  - A new human myeloma cell line, OPM-6, was established from the peripheral blood
      of a patient with advanced IgG-kappa plasma cell leukemia. Cytogenetic and
      phenotypic analysis confirmed that the cells were derived from the patient's
      leukemic cells. Insulin-like growth factor-1 (IGF-1) acts as an autocrine growth
      factor in these cells. In addition, OPM-6 cells were particularly sensitive to
      dexamethasone (DEX), when endogenous IGF-1 was blocked. Under these conditions,
      >95% of the DEX-treated cells died within 36 h. Therefore, OPM-6 represents a
      potentially powerful tool for the analysis of the molecular mechanisms of DEX
      induced apoptosis, because it is possible to easily analyze the direct effects of
      DEX using this system. Using this culture system of OPM-6, we demonstrated that
      the treatment with DEX plus a monoclonal antibody to the human IGF-1 receptor
      (alphaIGF-1R) leads to the down-regulation of the gene expression of Bcl-xL, an
      antiapoptotic gene, and the activation of CPP32 during this apoptotic process.
      IFN-alpha as well as IL-6 prevented DEX plus alphaIGF-1R-induced apoptosis, and
      this prevention was blocked by the mitogen-activated protein kinase kinase
      inhibitor, PD098059, or the phosphatidylinositol 3-kinase inhibitor, wortmannin.
      Therefore, both IL-6 and IFN-alpha blocked DEX plus alphaIGF-1R-induced apoptosis
      through activation of the mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase pathways.

PMID- 10945641
TI  - Characterization of bile salt-induced apoptosis in colon cancer cell lines.
AB  - Bile salts have been shown to be involved in the etiology of colorectal cancer.
      Although there is a large body of evidence for bile salts as a cocarcinogen in
      azoxymethane-induced colorectal cancer, bile salt-induced apoptosis of colorectal
      cancer cells has not yet been studied in detail. Therefore, we investigated the
      effects of different bile salts on apoptosis and apoptotic signaling in colon
      cancer cell lines. Incubation of colorectal cancer cell lines with physiological
      concentrations of deoxycholic acid led to a dramatic induction of apoptosis.
      Caspase cleavage and caspase activation occurred as early as 30 min after the
      addition of deoxycholate. Caspase-2 (Ich-1, Nedd2), caspase-3 (CPP-32, YAMA,
      Apopain), caspase-7 (Mch-3, ICE-LAP-3), and caspase-8 (FLICE, Mach-1, Mch5) are
      activated in HT-29, whereas caspase-1 (ICE) remained intact. Caspase activation
      and cellular apoptosis induced by bile salts were reversed by broad spectrum and
      selective caspase inhibitors. As opposed to hepatocyte death mediated by bile
      acids, CD95 was not involved in deoxycholate-induced apoptosis. The
      cytoprotective effect of ursodeoxycholic acid in hepatocytes or other tumor cell
      lines, which is mediated by inhibiting the mitochondrial permeability transition,
      was not observed in colon cancer cell lines as well. This points to distinct
      intracellular functions of ursodeoxycholate in different cancer cell types. Here
      we describe the specificity of bile salt-induced apoptosis in colon cancer cell
      lines. Differences from hepatocytes are shown. Bile acid-specific caspase
      activation is part of the apoptotic pathway induced by bile salts in colon cancer
      cell lines. Furthermore, a lack of cytoprotective function of ursodeoxycholate in
      these cells is demonstrated. Our data raise questions as to the role of bile
      salts in colorectal carcinogenesis.

PMID- 10945642
TI  - Scatter factor/hepatocyte growth factor protects against cytotoxic death in human
      glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways.
AB  - We have shown recently that the multifunctional growth factor, scatter
      factor/hepatocyte growth factor (SF/HGF), and its receptor c-met enhance the
      malignancy of human glioblastoma through an autocrine stimulatory loop (R.
      Abounader et al., J. Natl. Cancer Inst., 91: 1548-1556, 1999). This report
      examines the effects of SF/HGF:c-met signaling on human glioma cell responses to
      DNA-damaging agents. Pretreating U373 human glioblastoma cells with recombinant
      SF/HGF partially abrogated their cytotoxic responses to gamma irradiation,
      cisplatin, camptothecin, Adriamycin, and Taxol in vitro. This cytoprotective
      effect of SF/HGF occurred at least in part through an inhibition of apoptosis, as
      evidenced by diminished terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling index and reduced DNA laddering. Anti-c-met U1/ribozyme gene
      transfer inhibited the ability of SF/HGF to protect against single-strand DNA
      breakage, DNA fragmentation, and glioblastoma cell death caused by DNA-damaging
      agents, demonstrating a requirement for c-met receptor function. Phosphorylation
      of the cell survival-promoting kinase Akt (protein kinase B) resulted from SF/HGF
      treatment of U373 cells, and both Akt phosphorylation and cell survival induced
      by SF/HGF were inhibited by phosphatidylinositol 3-kinase inhibitors but not by
      inhibitors of mitogen-activated protein kinase kinase or protein kinase C.
      Cytoprotection by SF/HGF in vitro was also inhibited by transient expression of
      dominant-negative Akt. Transgenic SF/HGF expression by intracranial 9L
      gliosarcomas reduced tumor cell sensitivity to gamma irradiation, confirming the
      cytoprotective effect of SF/HGF in vivo. These findings demonstrate that c-met
      receptor activation by SF/HGF protects certain glioblastoma cells from DNA
      damaging agents by activating phosphoinositol 3-kinase-dependent and Akt
      dependent antiapoptotic pathways.

PMID- 10945643
TI  - Effects of a pure antiestrogen on apoptosis and proliferation within human breast
      ductal carcinoma in situ.
AB  - Adjuvant antiestrogen (AE) therapy has been proposed for all women with ductal
      carcinoma in situ (DCIS). However, many cases of DCIS are of the high-grade,
      estrogen receptor (ER)-negative subtype that are unlikely to respond to AE
      treatment. Hormonal agents work by increasing apoptosis and/or decreasing cell
      proliferation; therefore, we studied the effect of a pure AE on levels of
      apoptosis and proliferation in human DCIS xenografts using an in vivo model.
      Women (n = 23) with mammographic microcalcification suggestive of DCIS were
      identified at the time of surgery (day 0), a sample of representative tissue was
      obtained, divided into multiple 2x2x1-mm xenografts, and implanted s.c. into
      female BALB/c nu/nu mice (eight xenografts/mouse). Day 0 grafts underwent
      immunohistochemical assessment of ER status. Fourteen days after implantation,
      four xenografts were retrieved and mice were randomly divided into one of three
      treatment groups: (a) insertion of a slow release 2-mg 17beta-estradiol pellet;
      (b) weekly 5-mg injections of the pure AE Faslodex (Zeneca Pharmaceuticals); and
      (c) injections of a control vehicle oil alone. After 2 weeks of treatment, the
      remaining four xenografts were retrieved from each mouse. Retrieved xenografts
      containing DCIS were assessed for morphological evidence of apoptotic cell death
      [apoptotic index (AI)] and cell proliferation (by immunohistochemical detection
      of the Ki67 proliferation antigen LI). Both AI and LI were higher in the day 0
      specimens of 16 ER- DCIS lesions compared with 7 ER+ DCIS lesions (mean values,
      1.47% versus 0.32% and 20.6% versus 3.1%; both P<0.0001). AI and LI values within
      ER- DCIS did not differ between xenografts exposed to 17beta-estradiol or AE
      treatment compared with the controls or pretreatment values (mean AI and LI in
      estradiol-treated, antiestrogen-treated, and control groups 1.04% versus 0.98%
      versus 1.29% and 17.2% versus 20.5% versus 17.7% respectively). In contrast,
      treatment of mice bearing ER+ DCIS xenografts with 17beta-estradiol raised both
      the AI (1.03% versus 0.40%, P = 0.03) and LI (11.0% versus 5.1%, P = 0.007)
      compared with controls. AE therapy of ER+ DCIS xenografts did not affect
      proliferation but resulted in higher apoptosis than in controls (0.9% versus 0.4%
      respectively, P = 0.04). AE therapy should be reserved for patients with estrogen
      receptor positive DCIS.

PMID- 10945645
TI  - A mathematical model of the stress induced during avascular tumour growth.
AB  - In this paper a mathematical model is developed to describe the effect of
      nonuniform growth on the mechanical stress experienced by cells within an
      avascular tumour. The constitutive law combines the stress-strain relation of
      linear elasticity with a growth term that is derived by analogy with thermal
      expansion. To accommodate the continuous nature of the growth process, the law
      relates the rate of change of the stress tensor to the rate of change of the
      strain (rather than relating the stress to the strain directly). By studying
      three model problems which differ in detail, certain characteristic features are
      identified. First, cells near the tumour boundary, where nutrient levels and cell
      proliferation rates are high, are under compression. By contrast, cells towards
      the centre of the tumour, where nutrient levels are low and cell death dominant,
      are under tension. The implications of these results and possible model
      developments are also discussed.

PMID- 10945644
TI  - Human papillomavirus type 16 E6 and E7 proteins inhibit differentiation-dependent
      expression of transforming growth factor-beta2 in cervical keratinocytes.
AB  - Infection with high-risk human papillomaviruses (HPVs) represents a major risk
      factor for the development of cervical cancer. The HPV-16 E6 and E7 proteins are
      highly expressed in differentiating keratinocytes, where they inactivate the p53
      and retinoblastoma (pRb) proteins, two important transcriptional regulators. We
      have used cDNA expression arrays to identify global alterations in gene
      expression induced by E6 and E7 in differentiating cultures of human cervical
      keratinocytes. We show that E6 and E7 decrease expression of TGF-beta2 mRNA and
      alter expression of multiple TGF-beta-responsive genes involved in cell cycle
      regulation, apoptosis, and tissue remodeling. E6 and E7 inhibited expression of
      TGF-beta2 RNA 7-fold (relative effectiveness, E6/ E7 > E6 > E7 > control) and
      decreased secretion of biologically active TGF-beta2 by 70-80% (reduced from 70
      to 10 pg/10(6) cells/24 h). Downregulation occurred through p53- and pRb
      dependent pathways. In contrast, E6 and E7 did not alter expression of TGF-beta1
      and TGF-beta3. Down-regulation of TGF-beta2 was biologically relevant because the
      addition of recombinant cytokine (10-200 pg/ml) to E6/E7-expressing cells
      restored expression of TGF-P-responsive genes, inhibited growth of keratinocytes,
      and decreased immortalization by E6 and E7. These results suggest that TGF-32-
      and TGF-3-responsive genes are important targets for the HPV-16 E6 and E7
      oncoproteins in differentiating cervical keratinocytes.

PMID- 10945646
TI  - Linear stability criteria for population models with periodically perturbed
      delays.
AB  - We examine some simple population models that incorporate a time delay which is
      not a constant but is instead a known periodic function of time. We examine what
      effect this periodic variation has on the linear stability of the equilibrium
      states of scalar population models and of a simple predator prey system. The case
      when the delay differs from a constant by a small amplitude periodic perturbation
      can be treated analytically by using two-timing methods. Of particular interest
      is the case when the system is initially marginally stable. The introduction of
      variation in the delay can then have either a stabilising effect or a
      destabilizing one, depending on the frequency of the periodic perturbation. The
      case when the periodic perturbation has large amplitude is studied numerically.
      If the fluctuation is large enough the effect can be stabilising.

PMID- 10945647
TI  - A simple SIS epidemic model with a backward bifurcation.
AB  - It is shown that an SIS epidemic model with a non-constant contact rate may have
      multiple stable equilibria, a backward bifurcation and hysteresis. The
      consequences for disease control are discussed. The model is based on a Volterra
      integral equation and allows for a distributed infective period. The analysis
      includes both local and global stability of equilibria.

PMID- 10945648
TI  - Stability analysis of the partial selfing selection model.
AB  - We undertake a detailed study of the one-locus two-allele partial selfing
      selection model. We show that a polymorphic equilibrium can exist only in the
      cases of overdominance and underdominance and only for a certain range of selfing
      rates. Furthermore, when it exists, we show that the polymorphic equilibrium is
      unique. The local stability of the polymorphic equilibrium is investigated and
      exact analytical conditions are presented. We also carry out an analysis of local
      stability of the fixation states and then conclude that only overdominance can
      maintain polymorphism in the population. When the linear local analysis is
      inconclusive, a quadratic analysis is performed. For some sets of selective
      values, we demonstrate global convergence. Finally, we compare and discuss
      results under the partial selfing model and the random mating model.

PMID- 10945650
TI  - Coronary vasomotor disorders during hypoxia-reoxygenation: do calcium channel
      blockers play a protective role?
AB  - During heart surgery, myocardial dysfunction may occasionally appear when
      extracorporeal circulation is discontinued, causing serious haemodynamic
      disorders. Many mechanisms are involved in this hypoxia-reoxygenation syndrome.
      The aim of this experimental study was to characterize the vasomotor disorders
      that take place in the isolated porcine coronary artery during in vitro hypoxia
      reoxygenation and to analyse the effect of nifedipine on them. Rings of porcine
      coronary artery were placed in an organ chamber connected to a system that
      recorded isometric forces. The vascular rings were divided into two groups:
      control group (no nifedipine) and study group (nifedipine, 10(-6) mol/l). The
      vascular rings were precontracted with 30 mmol/l KCl and then hypoxia
      reoxygenation was induced. Control arterial rings showed important changes in
      coronary vasomotor tone: severe hypoxic contraction (from 14.48+/-1.16 g of
      stable contraction to 17.6+/-0.44 g after the imposition of hypoxia), and
      transient vasodilation during reoxygenation (69.9+/-10.1% of the maximum
      contraction achieved). The nifedipine group experienced a slow, progressive,
      vasodilation throughout the whole experiment (73+/-3.5% of the maximum
      contraction). Neither hypoxic vasospasm nor fluctuations of the coronary vascular
      tone occurred. Thus, at the end of the hypoxia, the control vessels presented a
      degree of contraction similar to the initial level. However, in the rings treated
      with nifedipine, the percentage of dilation was 73+/-3.5% (P<0.05). In the
      isolated porcine coronary artery with intact endothelium undergoing a situation
      of hypoxia-reoxygenation, we have detected transient vasoconstriction during the
      first period of hypoxia, followed by vasodilation during reoxygenation. The
      intracoronary administration of nifedipine prior to the imposition of hypoxia
      prevents hypoxic contraction, achieving a greater and more stable degree of
      coronary vasorelaxation during the complete process of hypoxia-reoxygenation.

PMID- 10945649
TI  - Heat-shock preconditioning reduces oxidative protein denaturation and ameliorates
      liver injury by carbon tetrachloride in rats.
AB  - Membrane lipids and cytosolic proteins are major targets of oxidative injury.
      This study examined the effect of heat-shock preconditioning associated with the
      induction of heat-shock protein 72 on liver injury, from the aspect of lipid
      peroxidation and protein denaturation after carbon tetrachloride (CCl4)
      administration in rats--one of the representative oxidative injuries. Male Wistar
      rats were divided into two groups, group HS (preconditioned by heat exposure) and
      group C (not preconditioned). Expression of HSP72 in the liver tissue was
      confirmed by Western blot analysis. After a 48-h recovery period, all rats were
      given CCl4 intragastrically. Liver damage was assessed by measuring serum liver
      related enzyme levels and adenine nucleotide concentration in the liver tissue.
      Lipid peroxidation and protein denaturation were evaluated by measuring
      tiobarbituric acid reactive substances (TBARS) and by immunohistochemical
      staining of 4-hydroxy-2-nonenal(HNE)-modified proteins in the liver. Survival
      rates of the rats after CCl4 administration were also compared. Expression of
      HSP72 was clearly detected in group HS, but not in group C. Heat-shock
      preconditioning significantly improved the survival rate, suppressed the increase
      in liver-related enzyme levels and maintained adenosine triphosphate levels
      (P<0.01 each). HNE-modified proteins--denatured proteins by free radical attack-
      were significantly less stained in group HS than in group C (P<0.05). However,
      TBARS levels did not differ between groups. Because heat-shock preconditioning
      did not alter TBARS levels but reduced HNE-modified proteins in association with
      the expression of HSP72, it is suggested that HSP72 did not prevent lipid
      peroxidation but decreased the lipid peroxidation-induced denaturation of
      proteins. This seemed to be a mechanism of heat-shock preconditioning to
      ameliorate oxidative liver injury.

PMID- 10945651
TI  - One-lung flooding for video-assisted thoracoscopic surgery in animal experiments
      on pigs--oxygenation and intrapulmonary shunt.
AB  - Unilateral flooding of the lung after intubation with a double-lumen tube makes
      intraoperative sonography of the lung during video-assisted thoracoscopic surgery
      possible. After flooding with 15 ml/kg, the arterial partial oxygen pressure
      (with FiO2=1.0) is higher than that in total atelectasis by about 100 mmHg, while
      it is only slightly less than that during bilateral lung ventilation. Compared to
      total atelectasis, lung flooding reduces the pulmonary right-to-left shunt
      volume. The pulmonary function normalizes within 8 h after the operation.

PMID- 10945652
TI  - Cellular distribution and phototoxicity of benzoporphyrin derivative and
      Photofrin.
AB  - Photodynamic therapy (PDT) induces cell-membrane damage and alterations in cancer
      cell adhesiveness, an important parameter in cancer metastasis. These alterations
      result from cell sensitivity to photosensitizers and the distribution of
      photosensitizers in cells. The efficacy of photosensitizers depends on their
      close proximity to targets and thus on their pharmacokinetics at the cellular
      level. We studied the cellular distribution of photosensitizers with a confocal
      microspectrofluorimeter by analysing the fluorescence emitted by benzoporphyrin
      derivative-monoacid ring A (BPD-MA) and Photofrin relative to their cell
      sensitivity. Two cancer cell lines of colonic origin, but with different
      metastatic properties, were used: PROb (progressive) and REGb (regressive). For
      BPD-MA (1.75 microg/ml), maximal fluorescence intensity (8,300 cts) was reached
      after 2 h for PROb and after 1 h (4,900 cts) for REGb. For Photofrin (10
      microg/ml), maximal fluorescence intensity (467 cts) was reached after 5 h for
      PROb and after 3 h (404 cts) for REGb. Intracellular studies revealed stronger
      cytoplasmic than nuclear fluorescence for both BPD and Photofrin. Both of the
      sensitizers induced a dose-dependent phototoxicity; LD50 with BPD-MA was 93.3
      ng/ml for PROb and 71.1 ng/ml for REGb, under an irradiation of 10 J/cm2. With
      Photofrin, LD50 was 1,270 ng/ml for PROb and 1,200 ng/ml for REGb under an
      irradiation of 25 J/cm2. The photosensitizer effect within PROb and REGb cancer
      cells was assessed by incorporation kinetics and toxicity-phototoxicity tests.
      The intracellular concentration of the photosensitive agent was one important
      factor in the effectiveness of PDT, but not the only one contributing to the
      photodynamic effect. In conclusion, this study showed that there was a clear
      difference between sensitizer uptake and phototoxicity, even in cancer cells of
      the same origin. This could induce cell-killing heterogeneity in clinics.

PMID- 10945653
TI  - Biodistribution of 99mTc-glutathione in mice with osteosarcoma: effect of gamma
      irradiation on tumour uptake.
AB  - The aim of this study was to determine the efficacy of 99mTc-glutathione (GSH) in
      scintigraphic demonstration of osteosarcoma tumour in mice and the effect of
      gamma irradiation of tumour on tumour uptake of 99mTc-GSH. The biodistribution of
      99mTc-GSH was studied in 30 Balb C mice 3 weeks after isotransplanting
      osteosarcoma OTS-64 in their thighs. The mice were injected with 400 microCi of
      99mTc-GSH in 0.1 ml through the tail vein. They were equally divided into two
      groups. In the second group the tumours were subjected to gamma irradiation for
      10 min (20 Gy). The mice in both groups were killed at 1, 3 and 6 h. Scintigrams
      were obtained at each time point. The organs, tumours, some muscle and some blood
      were removed, weighed and assayed for radioactivity. Tumour, liver and muscle
      sections were also obtained for gross autoradiographic studies. The tumours were
      well visualized on scintigrams. The tumour uptake values as a function of time
      after injection were 3.27+/-0.80, 1.53+/-0.69, and 1.51+/-0.55 for the control
      and 5.18+/-1.28, 0.399+/-0.120, and 1.67+/-1.05%/g for the irradiated groups at
      1, 3 and 6 h, respectively. The tumor-to-muscle concentration ratios were 34.03+/
      12.2, 21.4+/-11.3 and 18.7+/-11.4 for the control and 18.8+/-7.2, 3.63+/-1.9, and
      24.1+/-9.0 for the irradiated groups, respectively. The gross autoradiographic
      images of tumour sections indicated focal sites of increased uptake within tumour
      tissue, indicating the presence of necrotic areas. In conclusion, 99mTc-GSH
      accumulated in osteosarcoma and resulted in high tumour-to-other tissue
      concentration ratios in mice. The increase in uptake values after tumour
      irradiation might be a result of increased demand of tumour cells for GSH
      attributable to its well-known biological function as a reducing agent in
      addition to increased blood flow and capillary permeability in malignant tissues.

PMID- 10945654
TI  - Improvements in adenoviral vector technology: overcoming barriers for gene
      therapy.

PMID- 10945655
TI  - Altering the pathway to human gene therapy.

PMID- 10945656
TI  - Neuronal migration defects of the cerebral cortex: a destination debacle.
AB  - Disruptions in neuronal migration have been postulated as the basis for many
      cerebral malformations including lissencephaly, cortical heterotopia, and double
      cortex. Recently, the genetic basis for some of these disorders has been
      identified. In this review, we highlight recent advances in our understanding of
      the molecular mechanisms of neuronal migration and its relationship to cerebral
      cortical development and neuronal migration disorders. This has allowed us to
      begin categorizing specific malformations based on their molecular etiology.

PMID- 10945657
TI  - Genetic landmarks through philately--Thomas Hunt Morgan (1866-1945).

PMID- 10945658
TI  - Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and
      molecular analysis.
AB  - The polydactyly, imperforate anus, vertebral anomalies syndrome (PIV, OMIM
      174100) was determined as a distinct syndrome by Say and Gerald in 1968 (Say B,
      Gerald PS. Lancet 1968: 2: 688). We noted that the features of PIV overlap with
      the VATER association and Pallister-Hall syndrome (PHS, OMIM 146510), which
      includes polydactyly, (central or postaxial), shortened fingers, hypoplastic
      nails, renal anomalies, imperforate anus, and hypothalamic hamartoma. Truncation
      mutations in GL13, a zinc finger transcription factor gene, have been shown to
      cause PHS. We performed a molecular evaluation on a patient diagnosed with PIV,
      whose mother, grandfather, and maternal aunt had similar malformations. We
      sequenced the GLI3 gene in the patient to determine if she had a mutation. The
      patient was found to have a deletion in nucleotides 2188-2207 causing a
      frameshift mutation that predicts a truncated protein product of the gene. Later
      clinical studies demonstrated that the patient also has a hypothalamic hamartoma,
      a finding in PHS. We concluded that this family had atypical PHS and not PIV.
      This result has prompted us to re-evaluate the PIV literature to see if PIV is a
      valid entity. Based on these data and our examination of the literature, we
      conclude that PIV is not a valid diagnostic entity. We conclude that patients
      diagnosed with PIV should be reclassified as having VACTERL, or PHS, or another
      syndrome with overlapping malformations.

PMID- 10945659
TI  - Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct
      disorder.
AB  - In a previous study (Comings DE et al. Comparison of the role of dopamine,
      serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder.
      Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196) we
      examined the role of 20 dopamine, serotonin and norepinephrine genes in attention
      deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and
      conduct disorder (CD), using a multivariate analysis of associations (MAA)
      technique. We have now brought the total number of genes examined to 42 by adding
      an additional 22 candidate genes. These results indicate that even with the
      inclusion of these additional genes the noradrenergic genes still played a
      greater role in ADHD than any other group. Six other neurotransmitter genes were
      included in the regression equation - cholinergic, nicotinic, alpha 4 receptor
      (CHNRA4), adenosine A2A receptor (ADOA2A), nitric oxide synthase (NOS3), NMDAR1,
      GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized
      hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P
      450), ESR1, and INS (p = 0.005). This is consistent with our prior studies
      indicating a role of the androgen receptor (AR) gene in a range of externalizing
      behavors. We propose that the MAA technique, by focusing on the additive effect
      of multiple genes and on the cummulative effect of functionally related groups of
      genes, provides a powerful approach to the dissection of the genetic basis of
      polygenic disorders.

PMID- 10945660
TI  - United Kingdom experience with presymptomatic testing of individuals at 25% risk
      for Huntington's disease.
AB  - Between 1994 and 1998, the 23 UK genetics departments, which form the UK
      Huntington's Disease Consortium, have undertaken 161 direct mutation adult
      predictive tests on individuals whose at-risk parent was alive or had died
      without showing signs of Huntington's disease (HD) (5.7% of total UK tests). This
      study describes the number of requests for 25% risk predictive testing for HD in
      1994 (the first year in which direct testing was available in the UK), and also a
      descriptive survey of the first 85 tests. In total, 85 tests were performed in
      the first 2 years of direct mutation testing, ten (11.8%) tests were mutation
      positive, 73 (85.91%) were negative and two (2.3%) were equivocal. The at-risk
      parent was alive in 54 (63.5%) cases. Four of the ten mutation positive
      candidates had parents who were alive and therefore received a prediction through
      their child. All centres included a discussion about the effect of testing on the
      50% at-risk parent and all offered to see the parent for counselling. Of the 87
      applicants for testing during 1994, 31 (35.6%) withdrew, this is higher than the
      25% withdrawal rate for the 50% risk candidates. The candidates who withdrew were
      significantly younger and had more parents who were alive than those who
      continued with testing. Seven of the 31 candidates who withdrew from testing had
      at-risk parents who decided to be tested in the first instance. During the
      counselling process, issues were raised relating to pre-test agreements and
      family secrecy. This study indicates the importance of pre-test counselling and
      the involvement of the parent in the counselling process. 25% risk testing for HD
      is now being offered in the majority of UK centres. As more genes are identified
      for late-onset conditions, it is important that the complexities of 25% risk
      testing for late-onset conditions are not underestimated. This limited survey
      does not investigate how individual families cope with the psychological and
      social issues raised by this study and further research in this area is needed.

PMID- 10945661
TI  - Atypical movement disorders in the early stages of Huntington's disease: clinical
      and genetic analysis.
AB  - Huntington's disease (HD) is notably difficult to diagnose in the early stages.
      One reason is that the early clinical manifestations of HD vary widely and
      sometimes have an atypical onset. In this paper we primarily sought information
      on affected patients who initially presented with movement disorders other than
      chorea. We also investigated atypical motor presentations in relation to triplet
      CAG expansions. After reviewing the clinical records of two neurological centres,
      we identified patients with a final, documented diagnosis of HD and selected for
      study 205 patients according to their onset of motor manifestations. CAG repeats
      were analysed. Of the 205 patients studied, 15 had atypical motor symptoms at
      onset. In this group we identified three types of initial clinical manifestations
      other than chorea: parkinsonism, ataxia and dystonia. We conclude that HD
      patients may have different motor manifestations at the initiation of the
      illness. Patients with atypical movement disorders in the early stages have
      larger CAG expansions and an earlier age at onset than HD patients with typical
      onset chorea.

PMID- 10945662
TI  - Predictive testing for familial adenomatous polyposis in a rural South Indian
      community.
AB  - During the course of genome studies in a rural community in the South Indian
      state of Karnataka, DNA-based investigations and counselling for familial
      adenomatous polyposis (FAP) were requested via the community physician. The
      proposita died in 1940 and FAP had been clinically diagnosed in 2 of her 5
      children, both deceased. DNA samples from 2 affected individuals in the third
      generation were screened for mutations in the APC gene, and a frame-shift
      mutation was identified in exon 15 with a common deletion at codon 1061.
      Predictive testing for the mutation was then organized on a voluntary basis.
      There were 11 positive tests, including confirmatory positives on 2 persons
      diagnosed by colonoscopy, and to date surgery has been successfully undertaken on
      3 previously undiagnosed adults. The ongoing success of the study indicates that,
      with appropriate access to the facilities offered by collaborating centres,
      predictive testing is feasible for diseases such as FAP and could be of
      significant benefit to communities in economically less developed countries.

PMID- 10945663
TI  - Novel deletional mutation of the MEN 1 gene in a kindred with multiple endocrine
      neoplasia type 1.
AB  - MEN1 gene mutation in a Japanese kindred with multiple endocrine neoplasia type 1
      was examined. A heterozygous deletion involving 29 base pairs in exon 10
      (1606del29) was identified in the proband, and the same deletion was found in the
      affected family members. Most previously reported germline MEN1 gene mutations
      are nucleotide substitutions and small insertions/deletions, and a large deletion
      is rare. The hairpin structure mediated by an incomplete palindromic sequence at
      deletion termini is the most likely mechanism to be associated with the deletion
      in the present family.

PMID- 10945664
TI  - Cortical dysgenesis in 2 patients with chromosome 22q11 deletion.
AB  - Two patients with chromosome 22q11 deletion and cortical dysgenesis (gyral
      abnormalities) are reported in this study. One had unilateral clubfoot in
      addition to multiple features suggestive of the Di George syndrome (DGS), and the
      other presented with leg asymmetry and seizures, with subsequent recognition of
      the velo-cardio-facial syndrome (VCFS). In each patient, gyral abnormalities were
      identified in the hemisphere contralateral to the limb abnormality. A wide range
      of central nervous system abnormalities have been reported in DGS and VCFS,
      including three prior reports of gyral abnormalities (lissencephaly, microgyria).
      The 2 patients reported herein strengthen the association between the 22q11
      deletion spectrum and cortical dysgenesis, but the underlying pathogenetic
      mechanism (primary neural migration vs. vascular disruption) remains unclear.

PMID- 10945665
TI  - Sisters homozygous for the spinocerebellar ataxia type 6 (SCA6)/CACNA1A gene
      associated with different clinical phenotypes.
AB  - Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by a
      CAG repeat expansion in the CACNA1A gene. The neurodegeneration that occurs in
      CAG repeat diseases is considered to share a common mechanism that may result in
      the gain of a toxic function related to the expanded polyglutamine tracts.
      However, the phenotypic expression in homozygotes for CAG repeat diseases has
      been controversial, and is not clearly related to a gain of functional mechanism.
      We identified a Japanese family with two sisters who were homozygous for the SCA6
      with identical CAG repeat expansion (25/25). They showed an earlier age of onset
      (27 years in both) than their father (44 years), a heterozygote with an expanded
      allele showing the same CAG repeat length as the homozygotes (25/14).
      Interestingly, the two sisters showed differences in disease progression and
      severity, although the age of onset and CAG repeat length were identical. These
      findings strongly suggest that the gene dosage influences the age of onset, but
      other unknown factors are also important in the phenotypic expression of
      homozygous SCA6.

PMID- 10945666
TI  - Genetic variants of NRAMP1 and active tuberculosis in Japanese populations.
      International Tuberculosis Genetics Team.

PMID- 10945667
TI  - Low frequency of rhodopsin mutations in South African patients with autosomal
      dominant retinitis pigmentosa.

PMID- 10945668
TI  - Increased urolithiasis in patients with alkaptonuria in childhood.

PMID- 10945669
TI  - Pfeiffer syndrome type 2 associated with a single amino acid deletion in the
      FGFR2 gene.

PMID- 10945670
TI  - Polydactyly in 22q11 syndrome: should it be taken into account?

PMID- 10945671
TI  - Aspartame loading test in PKU heterozygous individuals bearing severe and
      moderate mutations.

PMID- 10945672
TI  - Complex permittivities of cyclomaltooligosaccharides (cyclodextrins) over
      microwave frequencies to 26 GHz.
AB  - Complex permittivities (epsilon*) for microwave radiation between 0.5 and 26 GHz
      have been determined for alpha-, beta-, and gamma-cyclodextrins in the solid
      state at room temperature. For the real component of epsilon*, maxima occur near
      0.6 GHz, and the relation beta > alpha > gamma is evident across the full
      frequency spectrum. Dielectric loss is significant only between 5 and 12 GHz for
      beta- and gamma-cyclodextrins with maxima near 7.5 GHz.

PMID- 10945674
TI  - Synthesis of a spacer-containing disaccharide fragment of Bordetella pertussis
      lipopolysaccharide.
AB  - The disaccharide 2-(p-aminophenyl)ethyl 4-O-(2-acetamido-2-deoxy-alpha-D
      glucopyranosyl)-2,3-diacetamido-2 ,3-dideoxy-alpha-D-mannopyranoside uronate,
      which is assumed to be a partial structure of the Bordetella pertussis
      polysaccharide, was synthesized starting from D-glucose and D-glucosamine,
      respectively. The major synthetic transformations were conversion of D
      glucosamine into the donor ethyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-thio-beta-D
      glucopyranoside and conversion of glucose, by a sequence involving 2,3-epoxide
      formation/opening, nucleophilic triflate displacement in the 3-position, and
      necessary protecting group manipulations, into the acceptor 2-(p
      trifluoroacetamidophenyl)ethyl 6-O-benzyl-2,3-diazido-2,3-dideoxy-alpha-D
      mannopyranoside. Coupling of the donor and acceptor units promoted by
      dimethyl(methylthio)sulfonium triflate followed by selective oxidation of the 6'
      position and deprotection gave the target disaccharide.

PMID- 10945673
TI  - Synthesis of single- and double-chain fluorocarbon and hydrocarbon galactosyl
      amphiphiles and their anti-HIV-1 activity.
AB  - Galactosylceramide (GalCer) is an alternative receptor allowing HIV-1 entry into
      CD4(-)/GalCer(+) cells. This glycosphingolipid recognizes the V3 loop of HIV
      gp120, which plays a key role in the fusion of the HIV envelope and cellular
      membrane. To inhibit HIV uptake and infection, we designed and synthesized
      analogs of GalCer. These amphiphiles and bolaamphiphiles consist of single and
      double hydrocarbon and/or fluorocarbon chain beta-linked to galactose and
      galactosamine. They derive from serine (GalSer), cysteine (GalCys), and
      ethanolamine (GalAE). The anti-HIV activity and cytotoxicity of these
      galactolipids were evaluated in vitro on CEM-SS (a CD4(+) cell line), HT-29, a
      CD4(-) cell line expressing high levels of GalCer receptor, and/or HT29
      genetically modified to express CD4. GalSer and GalAE derivatives, tested in
      aqueous medium or as part of liposome preparation, showed moderate anti-HIV-1
      activities (IC50 in the 20-220 microM range), whereas none of the GalCys
      derivatives was found to be active. Moreover, only some of these anti-HIV active
      analogs inhibited the binding of [3H]suramin (a polysulfonyl compound which
      displays a high affinity for the V3 loop) to SPC3, a synthetic peptide which
      contains the conserved GPGRAF region of the V3 loop. Our results most likely
      indicate that the neutralization of the virion through masking of this conserved
      V3 loop region is not the only mechanism involved in the HIV-1 antiviral activity
      of our GalCer analogs.

PMID- 10945675
TI  - Formation of unexpected substitution patterns in sulfonylbutylation of
      cyclomaltoheptaose promoted by host-guest interaction.
AB  - The distribution of substituents in sulfonylbutylethers of cyclomaltoheptaose
      (beta-cyclodextrin) formed in aqueous medium has been determined by gas
      chromatography after hydrolysis and formation of the permethylated
      sulfonylfluoride derivatives. In contrast to other etherification reactions of
      beta-cyclodextrin, preferred substitution in position 3 of the glucose units has
      been detected. From 1H NMR and microcalorimetric experiments, the formation of
      host-guest complexes by beta-cyclodextrin and the reagent 1,4-butane sultone in
      water became evident. This spatial preorganization presumably favors the reaction
      with the O-3. In contrast, in methyl sulfoxide preferred 2-O-alkylation was
      obtained, indicating that host-guest interaction does not influence
      regioselectivity in this solvent.

PMID- 10945676
TI  - Determination of the substituent distribution in O-sulfonylbutyl-(1-->4)-glucans.
AB  - A method has been developed to determine the distribution of substituents in the
      glucose units of sulfonylbutylethers of cyclomaltoheptaose (beta-cyclodextrin).
      This method involves hydrolysis of the glucosidic linkages, permethylation,
      formation of sulfonylchlorides and subsequent transformation to the permethylated
      sulfonylfluoride derivatives. The latter were thermostable and could be analyzed
      by GLC and identified by EI and CIMS. For confirmation, the 2-, 3-, and 6-O
      substituted standard compounds were independently synthesized and characterized
      by NMR and GLC-MS.

PMID- 10945677
TI  - A combined X-ray and NMR study of borate esters of furanoidic cis-1,2-diols.
AB  - Crystals of K[B(AnErytH(-2)2] x 2 H2O (AnEryt = 1,4-anhydroerythritol) form from
      aqueous alkaline solutions containing a double molar amount of diol over borate.
      The spiro-type monoanions are the main borate species in the mother liquors of
      crystallisation according to 11B and 13C NMR spectroscopy. Ribofuranosides form
      analogous borate esters using their 1,4-anhydroerythritol core. Crystals of
      Na[B(Me beta-D-Ribf 2,3H(-2))2] x 2 H2O were grown from alkaline methyl beta-D
      ribofuranoside solutions that had attacked boron-containing Duran vessels. NMR
      spectra show closely resembling borate-ester speciation in solutions of diols
      with the 1,4-anhydroerythritol core--1,4-anhydroerythritol itself, methyl beta-D
      ribofuranoside and guanosine.

PMID- 10945678
TI  - Analysis of different de-esterification mechanisms for pectin by enzymatic
      fingerprinting using endopectin lyase and endopolygalacturonase II from A. niger.
AB  - A series of pectins with different distribution patterns of methyl ester groups
      was produced by treatment with either plant (p-PME) or fungal pectin methyl
      esterases (f-PME) and compared with those obtained by base catalysed de
      esterification. The products generated by digestion of these pectins with either
      endopectin lyase (PL) or endopolygalacturonase II (PG II) from Aspergillus niger
      were analysed using matrix assisted laser desorption ionisation mass spectrometry
      (MALDIMS) and high-performance anion-exchange chromatography with pulsed
      amperometric or UV detection (HPAEC-PAD/UV). Time course analysis using MALDIMS
      was used to identify the most preferred substrate for each enzyme. For PL, this
      was shown to be fully methyl esterified HG whereas for PG II, long regions of HG
      without any methyl esterification, as produced by p-PME was the optimal
      substrate. The blockwise de-esterification caused by p-PME treatment gave a
      decrease of partly methylated oligomers in PL fingerprints, which did not effect
      the relative composition of partly methylated oligomers. PG II fingerprints
      showed a constant increase of monomers and oligomers without any methyl ester
      groups with decreasing degree of esterification (DE), but almost no change in the
      concentration of partly methylated compounds. PL fingerprints of f-PME and
      chemically treated pectins showed decreasing amounts of partly methyl esterified
      oligomers with decreasing DE, together with a relative shift towards longer
      oligomers. PG II fingerprints were characterised by an increase of partly
      methylated and not methylated oligomers with decreasing DE. But differences were
      also seen between these two forms of homogenous de-esterification. Introduction
      of a certain pattern of methyl ester distribution caused by selective removal of
      certain methyl ester groups by f-PME is the most reasonable explanation for the
      detected differences.

PMID- 10945679
TI  - Analysis of pectic epitopes recognised by hybridoma and phage display monoclonal
      antibodies using defined oligosaccharides, polysaccharides, and enzymatic
      degradation.
AB  - The structure of epitopes recognised by anti-pectin monoclonal antibodies (mAbs)
      has been investigated using a series of model lime-pectin samples with defined
      degrees and patterns of methyl esterification, a range of defined
      oligogalacturonides and enzymatic degradation of pectic polysaccharides. In
      immuno-dot-assays, the anti-homogalacturonan (HG) mAbs JIM5 and JIM7 both bound
      to samples with a wide range of degrees of methyl esterification in preference to
      fully de-esterified samples. In contrast, the anti-HG phage display mAb PAM1
      bound most effectively to fully de-esterified pectin. In competitive inhibition
      ELISAs using fully methyl-esterified or fully de-esterified oligogalacturonides
      with 3-9 galacturonic acid residues, JIM5 bound weakly to a fully de-esterified
      nonagalacturonide but JIM7 did not bind to any of the oligogalacturonides tested.
      Therefore, optimal JIM5 and JIM7 binding occurs where specific but undefined
      methyl-esterification patterns are present on HG domains, although fully de
      esterified HG samples contain sub-optimal JIM5 epitopes. The persistence of mAb
      binding to epitopes in pectic antigens, with 41% blockwise esterification (P41)
      and 43% random esterification (F43) subject to fragmentation by endo
      polygalacturonase II (PG II) and endo-pectin lyase (PL), was also studied. Time
      course analysis of PG II digestion of P41 revealed that JIM5 epitopes were
      rapidly degraded, but a low level of PAM1 and JIM7 epitopes existed even after
      extensive digestion, indicating that some HG domains were more resistant to
      cleavage by PG II. The chromatographic separation of fragments produced by the
      complete digestion of P41 by pectin lyase indicated that a very restricted
      population of fragments contained the PAM1 epitope while a (1-->4)-beta-D
      galactan epitope occurring on the side chains of pectic polysaccharides was
      recovered in a broad range of fractions.

PMID- 10945680
TI  - Quantification of the amount of galacturonic acid residues in blocksequences in
      pectin homogalacturonan by enzymatic fingerprinting with exo- and endo
      polygalacturonase II from Aspergillus niger.
AB  - A method to determine the amount of galacturonic acid in blocksequence (BS) in
      pectin homogalacturonan (HG) is described. The method is based on a combination
      of endopolygalacturonase II (endo-PG II) and exopolygalacturonase (exo-PG)
      digestion followed by quantification of the liberated galacturonic acid monomer.
      The amount of monomers released is directly related to the amount of non
      esterified galacturonic acid units located between two other non-esterified
      galacturonic acids units on the HG chain. The amount released for exo-PG
      digestion only corresponds to the BS located at the non-reducing end of the
      polymer. The difference between total- and exo-BS was calculated to be the amount
      of endo-BS located either within or on the reducing end of the HG. Three series
      of model pectins obtained by de-esterification of a high-ester pectin with either
      plant pectin methyl-esterase (p-PME, P-series), fungal pectin methyl-esterase (f
      PME, F-series) and chemical de-esterification using base (B-series) were analysed
      and compared with a fully de-esterified pectic acid sample obtained from the same
      raw material. Clear differences for the increase of the amounts of blocksequence
      could be seen between de-esterification of the P- and F-series samples supporting
      a blockwise and a homogenous de-esterification mechanism, respectively. f-PME and
      base treatment showed only minor differences in the increase of galacturonic acid
      units in BS, despite differences seen in their methyl-esterification pattern.
      Differences between the amounts of galacturonic acid located in exo- and endo-BS,
      provided evidence for the need of a certain start side or blocklength for p-PME
      to de-esterify blockwise.

PMID- 10945681
TI  - Interaction between carbohydrate residues of alpha1-acid glycoprotein
      (orosomucoid) and saturating concentrations of Calcofluor White. A fluorescence
      study.
AB  - Calcofluor White is a fluorescent probe that interacts with polysaccharides and
      is commonly used in clinical studies. Interaction between Calcofluor White and
      carbohydrate residues of alpha1-acid glycoprotein (orosomucoid) was previously
      followed by fluorescence titration of the Trp residues of the protein. A
      stoichiometry of one Calcofluor for one protein has been found [J.R. Albani and
      Y.D. Plancke, Carbohydr. Res., 318 (1999) 193-200]. Alpha1-acid glycoprotein
      contains 40% carbohydrate by weight and has up to 16 sialic acid residues. Since
      binding of Calcofluor to alpha1-acid glycoprotein occurs mainly on the
      carbohydrate residues, we studied in the present work the interaction between
      Calcofluor and the protein by following the fluorescence change of the
      fluorophore. In order to establish the role of the sialic acid residues in the
      interaction, the experiments were performed with the sialylated and asialylated
      protein. Interaction of Calcofluor with sialylated alpha1-acid glycoprotein
      induces a red shift of the emission maximum of the fluorophore from 438 to 450 nm
      at saturation (one Calcofluor for one sialic acid) and an increase in the
      fluorescence intensity. At saturation the fluorescence intensity increase levels
      off. Binding of Calcofluor to asialylated acid glycoprotein does not change the
      position of the emission maximum of the fluorophore and induces a decrease in its
      fluorescence intensity. Saturation occurs when 10 molecules of Calcofluor are
      bound to 1 mol of alpha1-acid glycoprotein. Since the protein contains five
      heteropolysaccharide groups, we have 2 mol of Calcofluor for each group. Addition
      of free sialic acid to Calcofluor induces a continuous decrease in the
      fluorescence intensity of the fluorophore but does not change the position of the
      emission maximum. Our results confirm the presence of a defined spatial
      conformation of the sialic acid residues, a conformation that disappears when
      they are free in solution. Dynamics studies on Calcofluor White and the
      carbohydrate residues of alpha1-acid glycoprotein are also performed at
      saturating concentrations of Calcofluor using the red-edge excitation spectra and
      steady-state anisotropy studies. The red-edge excitation spectra experiments show
      an important shift (13 nm) of the fluorescence emission maximum of the probe.
      This reveals that emission of Calcofluor occurs before relaxation of the
      surrounding carbohydrate residues occurs. Emission from a non-relaxed state means
      that the microenvironment of bound Calcofluor is rigid, inducing in this way the
      rigidity of the fluorophore itself, a result confirmed by anisotropy studies.

PMID- 10945682
TI  - New alpha-selective thermal glycosylation of acetyl-protected 2-acetamido-2-deoxy
      beta-D-glucopyranosyl diphenylphosphinate.
AB  - This paper describes new alpha-selective thermal glycosylation using acetyl
      protected 2-acetamido-2-deoxy-beta-D-glucopyranosyl diphenylphosphinate (4) as a
      glycosyl donor. When the glycosylation of 4 with 1-hexanol was carried out under
      various conditions, the conditions using trimethylsilyl trifluoromethanesulfonate
      as a promoter in nitromethane at reflux temperature were most suitable for the
      formation of the alpha anomer. The glycosylation of 4 with the other common
      alcohols gave corresponding alpha-glycosides in relatively high yields under the
      conditions. When cholesterol, a very steric hindered alcohol, was used as a
      glycosyl acceptor, alpha-glycoside was also produced predominantly.

PMID- 10945683
TI  - Homogeneous esterification of cellulose in the lithium chloride-N,N
      dimethylacetamide solvent system: effect of temperature and catalyst.
AB  - Commercial rayon grade cellulose was dissolved in the lithium chloride-N,N
      dimethylacetamide (LiCl-DMAc) solvent system and esterified with acetic anhydride
      using p-toluenesulfonyl chloride (p-TsCl) and pyridine as catalysts. The reaction
      temperature was varied from 28 to 70 degrees C and the time of reaction from 2 to
      24 h. Full substitution took place at 60 and 70 degrees C at respective reaction
      times of 10 and 8 h for p-TsCl, and 10 and 6 h for pyridine. Esterification of
      cellulose followed a second-order reaction path. The rate constants at different
      reaction temperatures and the activation energy for the reaction are reported.
      Mechanisms for these reactions using the two catalysts are also suggested. The
      degrees of substitution (DS) of the esters prepared using both catalysts show
      that pyridine is a better catalyst than p-TsCl. Molecular weights of the esters,
      determined viscosimetrically, show that some degradation in the cellulose chain
      occurred at a reaction temperature of 70 degrees C. Hence, the optimum
      temperature for esterification appears to be 50-60 degrees C at 10 h reaction
      time to obtain full degree of acetyl substitution.

PMID- 10945684
TI  - Selective laparoscopic probing for a contralateral patent processus vaginalis
      reduces the need for contralateral exploration in inconclusive cases.
AB  - BACKGROUND/PURPOSE: Repair of an indirect inguinal hernia is the most common
      procedure performed by pediatric surgeons, yet the need for contralateral
      exploration remains controversial. This prospective study evaluated the use of
      laparoscopy combined with the selective use of probing to determine the presence
      or absence of a contralateral patent processus vaginalis (CPPV). METHODS: A
      consecutive series of 75 of the author's patients presenting with a unilateral
      inguinal hernia were studied. Laparoscopy was performed through the known hernia
      sac with CO2 insufflation utilizing a 4-mm 70 degrees telescope to inspect the
      contralateral inguinal region. A patent processus was diagnosed when an obvious
      opening through the internal ring was identified. In some patients this
      evaluation was found to be inconclusive because of the inability to determine
      accurately the length of the patent processus or to rule out a patent processus
      obscured by a veil of peritoneum. This group of patients was then evaluated
      selectively with a silver probe placed under direct vision through a 14-gauge
      intravenous catheter placed through the abdominal wall on the side in question to
      manipulate the peritoneum and directly measure the length of the potentially
      patent processus. A patent processus greater then 1.5 cm was considered positive.
      RESULTS: A total of 54 patients (72%) had a conclusive laparoscopic evaluation of
      the contralateral inguinal region with a CPPV clearly absent in 38 and an obvious
      CPPV present in 16. A total of 21 patients (28%) had inconclusive laparoscopy
      finding and were evaluated further with probing. The probing technique changed
      the determination of a CPPV in 15 patients (12 positive to negative and 3
      negative to positive; P = .029, Fisher's Exact test). Probing resulted in a
      decrease in the overall rate of identification of a CPPV from 45% to 32%.
      CONCLUSION: In inconclusive cases, the addition of selective probing to the
      laparoscopic evaluation for a CPPV reduces the number of patent processus
      vaginalis found and the need for contralateral inguinal exploration.

PMID- 10945685
TI  - Posterior sagittal approach for repair of rectourethral fistula occurring after
      perineal surgery for imperforated anus at birth.
AB  - PURPOSE: Posterior sagittal approach was used for the repair of 11 cases of
      rectourethral fistula between 1992 and 1998. METHODS: All these patients had
      rectourethral fistula as a result of perineal procedure performed for imperforate
      anus at the time of birth. In addition to the fistula repair, an associated
      anorectal stenosis (3 cases) and urethral stricture 11 case) also were corrected
      with this approach. All the patients underwent surgery under cover of a
      protective colostomy. RESULTS: Successful repair was achieved in all patients,
      and the follow-up period ranged from 10 months to 7 years. As far as bladder and
      bowel control, urinary control was normal in all 11 patients, whereas bowel
      control was normal in 10 cases. One patient who had severe scarring of anal
      sphincters caused by infection in the previous surgery still suffers occasional
      perianal soiling after 18 months of follow-up. CONCLUSIONS: Posterior sagittal
      approach not only gives adequate exposure but also suits the basic principles of
      fistula repair, namely, completely separating the rectum from urethra and leaving
      normal rectal wall behind the urethral sutures thus eliminating the possibility
      of recurrence. In addition to fistula repair, one can also correct associated
      problems like anorectal stenosis or urethral stricture, and a mislocated rectum
      can be relocated within the sphincter complex.

PMID- 10945686
TI  - Mesenteric vascular occlusion resulting in intestinal necrosis in children.
AB  - PURPOSE: The records of 4 patients who had necrotic bowel secondary to acute
      mesenteric vascular occlusion affecting various levels of mesenteric vasculature
      were reviewed to determine the clinical manifestations, diagnostic
      investigations, predisposing factors, complications, and outcome of mesenteric
      vascular thrombosis in children. METHODS: The medical records of the patients (3
      boys, 1 girl) treated between 1981 and 1996, inclusive, for bowel infarction
      secondary to mesenteric vascular thrombosis, were reviewed with regard to signs
      and symptoms, laboratory tests, radiological investigations, surgical findings,
      histopathologic examinations, and outcome. RESULTS: The ages of the patients
      ranged between 1 and 14 years with a mean age of 8.2 years. Initial symptoms,
      present in all patients, were abdominal pain, abdominal distension, and
      tenderness. Laboratory and radiological findings including abdominal radiographs
      and abdominal ultrasonography were nondiagnostic. Selective superior mesenteric
      angiography showed complete obliteration of the superior mesenteric artery with
      absence of venous return in 1 case. Three patients with massive intestinal
      necrosis died of multiorgan failure or the complications of short bowel syndrome.
      Histological examination of the resected intestinal segments showed the typical
      findings of polyarteritis nodosa in 2 patients. One patient had a previous
      history of right femoral vein thrombosis, whereas 1 patient had no known
      underlying disorders predisposing vascular thrombosis. CONCLUSIONS: Mesenteric
      vascular occlusion is a rare but serious disease leading to death in children.
      The patients present with similar clinical signs, most frequent and important are
      acute abdominal pain, vomiting, and distension. Mesenteric vascular occlusion is
      a rare cause of acute abdomen in childhood, which requires urgent diagnosis and
      intervention. In suspected mesenteric vascular insufficiency, angiography should
      be performed followed by intraarterial thrombolytic infusion therapy in selected
      cases. When intestinal infarction is suspected, immediate surgical resection of
      compromised bowel is necessary with appropriate postoperative anticoagulation or
      treatment of any underlying disease.

PMID- 10945687
TI  - Individual and associated effects of length of inguinal canal and caliber of the
      sac on clinical outcome in children.
AB  - PURPOSE: The caliber of processus vaginalis is accepted to define the clinical
      outcome to be an inguinal hernia or hydrocele not based on any evaluation. The
      caliber of sacs and length of inguinal canals of boys and girls were evaluated to
      define the relation of sex, age, and the diagnosis with caliber of the sac and
      the length of inguinal canal. METHODS: A total of 217 inguinal canals in 24 girls
      and 112 boys with inguinal hernia, 30 boys with hydrocele or hydrocele of the
      cord, and 31 boys with undescended testis have been evaluated. Twenty patients
      had bilateral involvement. The length of inguinal canal, and the circumference of
      the sac were measured. A formula was developed to predict the length of inguinal
      canal according to the age and sex. The circumferences of the sacs, length of
      inguinal canals, and the ratios of the circumference to the length were compared
      according to the clinical pictures. RESULTS: The regression model of the
      relationship between the age and the length of the inguinal canal is an equation
      of third degree (inguinal canal in millimeters) = 0.0000119 x age 3 (months) -
      0.00292 x age 2 (months) + 0.3168 x age (months) + 19.979 (r2 = 0.47). Inguinal
      canal is longer in boys (25.133 and 27.996 mm; P = .018), and length does not
      differ among diagnoses but differs according to age showing a linear growth after
      24 months. Although the circumference as a sole parameter could classify only
      55.3% of boys correctly, the ratio of length of inguinal canal to circumference
      of the sac has been the significant parameter in classifying boys into 1 of 3
      groups including inguinal hernia, undescended testis, and hydrocele with a 70.2%
      success rate. CONCLUSIONS: Inguinal canal that shows a linear growth after 24
      months of age is longer in boys. Caliber is not the unique factor that determines
      the clinical outcome. Although the ratio of length of inguinal canal to the
      circumference of the sac defines the clinical picture best, even this parameter
      cannot classify the cases correctly. Therefore, some factors in addition to the
      caliber and length of inguinal canal might have roles in determining the clinical
      outcome.

PMID- 10945688
TI  - Laparoscopy in infants and children: a prospective study on feasibility and the
      impact on routine surgery.
AB  - BACKGROUND/PURPOSE: The feasibility of laparoscopy in children and its impact on
      routine pediatric surgery are not well established. The purpose of this study was
      to determine the role of laparoscopy in a university department of pediatric
      surgery. METHODS: All children undergoing laparoscopy during the period of 1 year
      were included in a prospective trial. Data on patients, the operation, technical
      problems, intraoperative events, and the postoperative course were documented
      using standardized questionnaires. All patients underwent at least 1 follow-up
      assessment 2 weeks after the operation. All conventional abdominal operations
      performed during the same period were analyzed for comparison purposes. RESULTS:
      Of 244 abdominal operations performed during the study period, 147 (60.2%) were
      laparoscopies. One hundred twenty-three (83.7%) of these included a laparoscopic
      operation, and 24 (16.3%) were diagnostic procedures. Of 26 types of laparoscopic
      operations 3 were performed more than 15 times (fundoplication, appendectomy,
      pyloromyotomy), and 9 types were performed once. Problems with instruments and
      devices led to a mean time loss of 15.1 minutes in 15.6% of the procedures. The
      conversion rate was 10.1% mainly because of complicated appendicitis. Fifty-six
      children (38.1%) weighed less than 10 kg, and the conversion rate did not
      correlate with the body weight. There was 1 (0.07%) intraoperative event. A small
      bowel perforation was identified immediately and resolved with an uneventful
      course. Postoperative complications included an incisional hernia in 3 children
      and an incisional leakage of liquor in 1 child with a ventriculoperitoneal drain.
      There was a reprolaps after laparoscopic correction of an ileostomy in 1 child
      and fever in another. In 3 newborns the diagnosis was missed during laparoscopy
      and had to be established by laparotomy later with an uneventful course. Primary
      conventional operations were mainly restricted to bowel resection and anastomosis
      performed in 52 of 97 laparotomies. CONCLUSIONS: The authors showed that 60% of
      abdominal operations in children can be performed via laparoscopy. Most types of
      laparoscopic operations are not performed frequently, but the feasibility of the
      technique in routine use is excellent. However, the performance of instruments
      should be improved further, and laparoscopy for establishing the diagnosis in
      newborns remains difficult.

PMID- 10945689
TI  - Infectious complications in critically injured children.
AB  - PURPOSE: Infection will complicate the care of a significant number of injured
      adults. Trauma is the leading cause of mortality in the pediatric population, yet
      little information is available regarding the incidence of infection in this
      group. This study evaluates infectious complications in the critically injured
      child. METHODS: All children admitted to the pediatric intensive care unit from
      an urban level-1 trauma center during an 80-consecutive-month period were
      studied. Infection was defined by Centers for Disease Control criteria and was
      identified by a retrospective review of the medical records. Demographic and
      clinical information, including microbiologic data, were compiled for all study
      patients. Data were analyzed using Student's (t)test or chi2 analysis where
      appropriate. RESULTS: Five hundred twenty-three children were at risk for
      infection during the study period. Seventy-eight infections were documented in 53
      children (incidence, 10.1%). Nosocomial infections accounted for 78% of these
      with a majority (85%) being device associated. Common infections in this group
      included lower respiratory (n = 35), primary bloodstream (n = 10), and urinary
      tract (n = 7). Trauma-related infections were primarily wound (n = 9),
      intraabdominal (n = 3), or central nervous system (n = 3). Bacterial pathogens
      predominated, and the most frequent microorganisms recovered were Staphylococcus
      aureus, Pseudomonas sp, and Haemophilus sp. Children with infectious
      complications were more severely injured (injury severity score [ISS] 24 versus
      17, P < .001) and had a longer hospital stay (21 days v 6 days, P < .001)
      compared with children without infection during the same period. Overall
      mortality rate for the study group was 5.7% and was not significantly different
      from children without infection. CONCLUSIONS: Infection is a significant source
      of morbidity in the critically injured child. Nosocomial infections predominate,
      and a majority of these are device related, emphasizing the need for continued
      vigilance toward prevention in this high-risk group.

PMID- 10945690
TI  - Pediatric surgery on the Internet: is the truth out there?
AB  - BACKGROUND: The enormous amount of unmonitored medical information on the
      Internet prompted this investigation into the quality of pediatric surgery
      information on the Internet. METHODS: The Internet was searched for information
      on diaphragmatic hernia (CDH), abdominal wall defects (AWD), pediatric inguinal
      hernia (IH), and pectus excavatum (PE). Websites were characterized, classified,
      and evaluated for completeness, accuracy and bias toward or against the medical
      profession. RESULTS: A total of 141 websites were evaluated (N(CDH) = 37, N(AWD)
      = 49, N(IH) = 26, N(PE) = 29). A total of 59.6% targeted medical professionals,
      and 46.8% targeted the lay population. A total of 58.2% described symptoms and
      diagnosis. Etiology, pathology, surgery, postoperative course, and prognosis each
      were addressed by under 40%. A total of 58.2% were accountable for the
      information presented. A total of 93.1% were incomplete, 75.7% contained accurate
      information, and 97.7% were positive or neutral toward medical treatment. Among
      diagnoses, CDH had the highest percentage of websites owned by academic
      institutions. PE had the highest percentage of websites owned by lay people. PE
      websites also were the least accurate. CONCLUSIONS: Internet information on
      pediatric surgery varies significantly in quality. Lay people own most websites
      targeted at the lay audience, and the information may not reflect the opinions of
      most pediatric surgeons. Increasing use of the Internet by parents seeking
      medical information warrants an organized approach to ensure complete and
      accurate information online.

PMID- 10945691
TI  - Compressive orthotics in the treatment of asymmetric pectus carinatum: a
      preliminary report with an objective radiographic marker.
AB  - BACKGROUND/PURPOSE: Pectus carinatum (PC) traditionally has been managed with
      surgical reconstruction. Compressive orthosis also has resulted in subjective
      improvement in this defect. The goal of the authors was to develop an alternative
      brace and an objective radiographic marker to monitor the effects of chest wall
      compression on sternal protrusion. METHODS: Baseline chest computed tomography
      (CT) scans were obtained for 5 teenage boys with chondrogladiolar type of PC. The
      angle at the point of greatest sternal rotation was measured as the baseline
      deformity. Compressive orthosis was initiated using a custom-fitted brace. Follow
      up chest CT scans were obtained to document change in sternal rotation. RESULTS:
      One patient was lost to follow-up after 6 months with subjective improvement.
      Another opted for surgical correction after 3 months, having shown a 16% decrease
      in sternal rotation preoperatively. Two patients showed subjective improvement
      corroborated by 33% and 44% decreases in sternal rotation. The fifth patient, who
      discontinued bracing after 1 month, showed a 25% increase 6 months later.
      CONCLUSIONS: Preliminary results indicate a potential role for compressive
      orthosis in the management of pectus carinatum. The objective radiographic marker
      described may be used to monitor the effects of growth or treatment with
      compressive orthosis.

PMID- 10945692
TI  - Congenital diaphragmatic hernia: a meta-analysis of mortality factors.
AB  - PURPOSE: The aim of this study was to review all available studies reported in
      the English-language literature from 1975 through 1998, and by meta-analysis
      assess the importance of prenatal diagnosis, associated malformations, side of
      hernia, timing of surgery, and study population on mortality rates in patients
      with congenital diaphragmatic hernia (CDH). METHODS: One-hundred-two studies were
      identified, and 51 studies (2,980 patients) fulfilled the prespecified inclusion
      criteria. Studies were grouped according to study population into: (I) fetuses
      diagnosed prenatally; (II) neonates admitted to a treatment center; and (III)
      population-based studies. RESULTS: Pooled total mortality rate was significantly
      higher in category I than in category III (75.6% v 58.2%, P < .001). Pooled
      hidden postnatal mortality rate (deaths before admittance to a treatment center)
      in population-based studies was 34.9%. Prenatally diagnosed patients in both
      category II and III had significantly higher mortality rates than those diagnosed
      postnatally. Mortality rates were significantly higher among CDH infants with
      associated major malformations compared with isolated CDH in all 3 categories. An
      increased mortality rate in right-sided CDH was found in category II and III.
      CONCLUSIONS: Prenatal diagnosis of CDH, presence of associated major
      malformations, and the study population have a major influence on mortality rate.
      The very high mortality rate in studies of fetuses with a prenatal diagnosis of
      CDH should be taken into account in prenatal counselling.

PMID- 10945694
TI  - The role of laparoscopy in the management of suspected recurrent pediatric
      hernias.
AB  - BACKGROUND: This report examines recurrent pediatric groin hernias and the role
      of diagnostic laparoscopy in the management of these recurrences. METHODS: A
      chart review of 19 children presenting with recurrent hernias was performed,
      analyzing the type of primary hernia, nature of recurrence, preexisting medical
      conditions, surgical complications at primary repair, and time to recurrence.
      Diagnostic laparoscopy (DL) was used during the remedial repair of the last nine
      patients. RESULTS: Seventeen indirect hernias were repaired during the primary
      repair, and 1 femoral hernia was identified. In one child, no inguinal hernia was
      identified at the initial operation. Overall, 11 recurrences were found to
      consist of indirect sacs, and 4 were found to have attenuation of the inguinal
      floor. Four additional recurrences were found to be femoral hernias. In only 1
      patient was a wound factor (infection) thought to play a role in the recurrence.
      Diagnostic laparoscopy in 9 patients found 4 (44%) to have unsuspected
      intraoperative findings. Four femoral hernias were identified (3 with unsuspected
      contralateral femoral hernias). Additionally, 1 unsuspected recurrence of an
      indirect sac was identified. CONCLUSIONS: Laparoscopy accurately identifies the
      nature of the defect in children with recurrent groin hernias, detecting
      unsuspected contralateral indirect, direct, or femoral hernias in 44% of those
      undergoing laparoscopy.

PMID- 10945693
TI  - Inhibition by an angiogenesis inhibitor, TNP-470, of the growth of a human
      hepatoblastoma heterotransplanted into nude mice.
AB  - BACKGROUND/PURPOSE: The effect of TNP-470, an angiogenesis inhibitor, on the
      growth of a hepatoblastoma transplanted into nude mice was examined. METHODS: A
      hepatoblastoma obtained from a 3-year-old girl was serially transplanted into
      nude mice subcutaneously, and the transplant tumors of the seventh and eighth
      generations were used for experiments. Expression of various markers in the
      tumors was examined immunohistochemically. TNP-470 was injected subcutaneously
      every other day into tumor-bearing mice from 3 weeks after tumor transplantation.
      The proliferation of tumor cells and endothelial cells was estimated by means of
      the bromodeoxyuridine labeling index. RESULTS: The original hepatoblastoma showed
      the histology of the epithelial type, consisting of both the fetal and embryonal
      subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti
      cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an
      antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors
      consisted of solid nests of tumor cells with numerous vascular lakes of various
      sizes, and showed positive staining with all antibodies that reacted positively
      with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and
      30 mg/kg body weight suppressed the tumor growth and the increase in the serum
      level of AFP dose dependently. Injections of TNP-470 also suppressed the
      proliferation of tumor cells and endothelial cells in the tumors. CONCLUSIONS:
      Hepatoblastomas maintained in nude mice retained the immunohistochemical
      characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth
      of hepatoblastomas transplanted into nude mice. TNP-470 may be worth
      investigating further as to its usefulness as a therapy for hepatoblastomas.

PMID- 10945695
TI  - Transanal endorectal coloanal surgery for Hirschsprung's disease: experience in
      two centers.
AB  - BACKGROUND/PURPOSE: Transanal mucosal proctectomy with low coloanal anastomosis
      has been used widely in the treatment of rectal malignancies, ulcerative colitis,
      and familial polyposis. The use of this technique for Hirschsprung's disease is a
      relatively new concept. The aim of this study was to evaluate and compare the
      results of transanal endorectal coloanal anastomosis (TECA) for Hirschsprung's
      disease from 2 centers. METHODS: All children who underwent TECA for
      Hirschsprung's disease at Alder Hey Children's Hospital, Liverpool, England from
      January 1995 to December 1998 (n = 41) and the Children's Hospital, Helsinki,
      Finland from June 1988 to December 1998 (n = 95) were evaluated. Patient
      demographics, age at diagnosis, initial management, length of aganglionic
      segment, and age at operation were documented. Postoperative complications and
      functional outcome were analyzed. RESULTS: Patient demographics were similar in
      the 2 centers. Age at diagnosis was less than 1 month in 71% of children at
      Liverpool, compared with 53% at Helsinki. Sixteen (39%) patients in Liverpool and
      75 (79%) patients in Helsinki underwent primary TECA without colostomy.
      Postoperative enterocolitis occurred in 14 of 136 patients (10%). An ischemic
      stricture of the colon was documented in 4 children in the Liverpool series, 2 of
      whom had TECA as a salvage procedure after a previously failed Duhamel pull
      through operation. Frequency of bowel movements, seen in the immediate
      postoperative period in most patients gradually improved with time from a median
      of 5 (range, 2 to 12) bowel movements a day at 3 months after TECA to 2 (range, 1
      to 6) bowel movements a day at 2 years' follow-up. Assessment of continence was
      possible in 51 of 136 patients (37%) over the age of 4 years. Thirty-nine
      children had normal bowel function giving an overall success rate of 76%.
      CONCLUSIONS: Transanal endorectal coloanal anastomosis is a good technique for
      treatment of Hirschsprung's disease with few operation-related complications.
      Based on the data emerging from these 2 centers the functional outcome is highly
      satisfactory and comparable with other established procedures.

PMID- 10945696
TI  - Long-term outcome of Boix-Ochoa and Nissen fundoplication in normal and
      neurologically impaired children.
AB  - PURPOSE: The aim of this study was to compare the results of Boix-Ochoa and
      Nissen fundoplication performed in the authors' department in normal and
      neurologically impaired children. METHODS: The medical records of all children
      who underwent fundoplication in the span of 10 years from 1988 to 1997 were
      reviewed. Boix-Ochoa procedure was the preferred operation before 1993. Since
      1993, the Nissen fundoplication has been used as the operation of choice for
      surgical antireflux treatment. RESULTS: A total of 109 fundoplications were
      performed during that period, of which 64.2% of the children involved were
      neurologically impaired. The Boix-Ochoa procedure and Nissen fundoplication were
      the 2 types of operations performed for antireflux surgical treatment. There were
      22 recurrences of gastroesophageal reflux, 14 in the neurologically impaired
      group and 6 in the normal group. All except 2 recurrences were after the Boix
      Ochoa procedure. Neurological impairment increased the morbidity rates after
      these procedures and dictated the effectiveness of the operation. Nissen
      fundoplication fared better in comparison with the Boix-Ochoa procedure in both
      the neurologically impaired and the normal group. CONCLUSIONS: Antireflux surgery
      is beneficial in children with significant gastroesophageal reflux, irrespective
      of their neurological status, although complications are more common in the
      neurologically impaired group. Nissen fundoplication is more effective and has
      fewer complications.

PMID- 10945697
TI  - Situs inversus and bowel malrotation: contribution of prenatal diagnosis and
      laparoscopy.
AB  - The authors report 3 different cases of prenatal diagnosis of situs inversus
      associated with bowel malrotation. Heterotaxy existed in 2 cardiosplenic
      syndromes (1 left and 1 right isomerism), and 1 isolated situs inversus. Bowel
      malrotation was detected at birth by ultrasonography and intestinal contrast
      study. Patients underwent laparoscopic LADD's procedure and abdominal exploration
      in the neonatal period. The authors advocate neonatal screening and early
      surgical management of bowel malrotation in prenatally diagnosed heterotaxic
      syndromes.

PMID- 10945698
TI  - Spontaneous regression of clinical inguinal hernias in preterm female infants.
AB  - PURPOSE: This is a prospective study of 8 clinically apparent inguinal hernias in
      7 preterm infant girls. METHODS: The diagnosis was made clinically and confirmed
      by ultrasonography, which also showed the contents of the hernia. RESULTS: One
      hernia contained an ovary, the other 7 intestinal loops. The hernias with only
      intestinal loops regressed spontaneously when the girls were between the ages of
      2 and 6 months postpartum. This was confirmed by ultrasonography. At follow-up 2
      to 6 years later there has been no recurrence. The hernia that contained the
      ovary did not regress, and hernia repair (confirming the presence of the ovary)
      was carried out uneventfully. CONCLUSIONS: The authors suggest that preterm
      infant girls with an inguinal hernia should have ultrasonography performed at
      presentation. Surgery probably will be required when the hernia contains
      structures such as an ovary. When the hernia contains only intestinal loops an
      expectant policy may be advisable. Larger studies are needed to validate these
      findings.

PMID- 10945699
TI  - Treatment of varicoceles in childhood and adolescence with Tauber's antegrade
      scrotal sclerotherapy.
AB  - PURPOSE: The aim of this study was to evaluate surgical complications and the
      outcome of grade II and III varicoceles treated with Tauber's antegrade scrotal
      sclerotherapy. METHODS: A total of 21 patients with a median age of 13 (range, 10
      to 21) years and left-sided grade II and III varicoceles were treated with
      Tauber's antegrade scrotal sclerotherapy and underwent follow-up over a median
      period of 23 months (range, 9 to 35). RESULTS: One grade II varicocele persisted
      after antegrade sclerotherapy for 6 months. After a second sclerotherapy 6 months
      later, no further recurrence was detected. One patient with a grade II to III
      varicocele had a grade I varicocele recurrence 14 months after operation. Three
      patients showed a slight hydrocele postoperatively. CONCLUSION: This limited
      series indicates that Tauber's antegrade scrotal sclerotherapy is a safe and
      effective treatment for grade II and III varicoceles in children and adolescents.

PMID- 10945701
TI  - Computer-generated three-dimensional morphology of the hepatic hilar bile ducts
      in biliary atresia.
AB  - BACKGROUND/PURPOSE: In biliary atresia (BA), although the intrahepatic bile ducts
      are reported to appear in the fetal configuration in about 20% to 60% of cases,
      information about the 3-dimensional (3-D) morphology of the hilar biliary
      structures is limited. The authors, therefore, have applied the technique of
      computer-generated 3-D reconstruction, to study the morphology of the hilar
      biliary structures in patients who have undergone biliary decompression. METHODS:
      Computer-generated 3-D reconstructions were performed from serial sections of the
      hepatic hilum of 4 BA patients and compared with those obtained from a 3-day old
      infant who had no apparent biliary disease but died of congenital diaphragmatic
      hernia (CDH) and with normal human fetal ductal plate at 11 weeks of gestation.
      RESULTS: In all 4 BA patients, the hilar bile ducts strongly resembled the ductal
      plate structures of the fetus rather than the bile ducts of the CDH infant. This
      leads the authors to suggest that these abnormal biliary structures are the
      result of improper ductal plate remodeling at the hepatic hilum. In 3 of the BA
      patients there were some tubular bile ducts that probably are the result of
      delayed and abnormal attempt at ductal plate remodeling.

PMID- 10945700
TI  - Functional development of the donor leg after vascularized fibula graft in
      childhood.
AB  - PURPOSE: To evaluate the effect of free vascularized fibula grafts on developing
      donor leg function, the authors reviewed their experience of procedures performed
      in children. METHODS: Over a 10-year period, 30 children (average age 7.2 years,
      without gender concern) underwent fibula harvest via an anterolateral approach.
      Graft length averaged 6.0 cm. Follow-up averaged 8 years. RESULTS: No vascular
      injury or shank dysplasia ensued. Neural injury occurred in 8 patients: to the
      profound peroneal nerve in 1 and to the superficial peroneal nerve in 7. Symptoms
      resolved spontaneously at 3 to 5 months in 6, but persisted in 2 patients in the
      latter group at 8 years' follow-up. Of 24 children who underwent rapid walking
      (200 m) followed by immediate stair climbing (50 steps), 2 (whose grafts were
      longer than average) had slight and 1 had obvious ankle pain. However, muscle
      strength and range of motion in the donor ankle were no different from values in
      the recipient leg in the 24 cases. X-ray findings showed that, with growth, the
      remaining 2 fibular segments in the donor leg became longer, but the length of
      the gap between did not change. Thus, the gap left by harvest became relatively
      shorter long after operation, benefiting the stability of the ankle joint in
      adulthood. CONCLUSION: Unlike free vascularized fibula grafts performed in
      adulthood, from which serious complications to the donor leg have been reported,
      the procedure performed in childhood appears not to have an adverse effect on
      functional development.

PMID- 10945702
TI  - An economic evaluation of sonographic examination of children with suspected
      appendicitis.
AB  - BACKGROUND/PURPOSE: Appendicitis is the most common surgical emergency presenting
      in the pediatric population. Approximately one third of these patients present
      with equivocal signs and symptoms frequently resulting in inpatient observation
      or additional diagnostic investigation. Although sonographic examination of
      patients with suspected appendicitis has been shown to be a highly accurate
      diagnostic modality, the cost effectiveness of this technology in the pediatric
      population has not been addressed. The economic value of this examination can be
      evaluated using a structured decision analysis. METHODS: The authors constructed
      a decision analysis model of treatment strategies for 2 groups of patients with a
      suspected diagnosis of acute appendicitis. Patients were categorized as either
      presenting with a "definitive acute abdomen" or "equivocal examination." Data
      drawn from published literature reports of the sensitivity and specificity of
      ultrasound, institution-specific cost data, and expert judgment were used to
      construct 2 decision trees. These data were used to determine the least costly
      diagnostic strategy for each group of patients, and sensitivity analysis
      performed to assess the robustness of the conclusions. RESULTS: The use of
      ultrasonography in patients with "an acute abdomen" is not cost efficient and
      results in average additional cost of $234 per patient. In patients with
      equivocal diagnoses who are discharged from the emergency room after a negative
      ultrasound examination finding results in an average cost savings of $260 when
      compared with admission and observation. Patients who are discharged without
      examination incur an average additional cost of $373 as a result of the high cost
      of a missed diagnosis resulting in a perforated appendix. CONCLUSION: The use of
      ultrasonography can be recommended for children with suspected appendicitis and
      equivocal examinations who are discharged from the emergency room after a
      negative examination result.

PMID- 10945703
TI  - Pyloric atresia: five new cases, a new association, and a review of the
      literature with guidelines.
AB  - BACKGROUND/PURPOSE: Pyloric atresia is an uncommon condition occurring in 1 of
      100,000 live births. When occurring in isolation, the clinical course usually is
      uncomplicated after surgical treatment. However, it may occur in association with
      other congenital abnormalities. The authors present 5 new cases, 3 of associated
      abnormalities including 1 of esophageal atresia and 2 of agenesis of the gall
      bladder and malrotation. Agenesis of the gall bladder has not been described
      previously in combination with pyloric atresia. The literature has been reviewed
      and guidelines are suggested for the management. METHODS: The case records of 4
      neonates who presented to the author's institution between January 1998 and June
      1999 and 1 who presented at another center in 1991 were reviewed. A Medline
      literature search was performed, and guidelines were developed for the management
      of this condition based on our cases and the literature review. RESULTS: Patients
      1 and 5 had no associated anomalies. Patient 2 had associated esophageal atresia,
      tracheoesophageal fistula, atrial septal defect, crossed renal ectopia,
      malrotation, and absent gall bladder. Patient 3 had a rectovestibular fistula,
      vaginal atresia, atrial septal defect, malrotation absent gallbladder, and absent
      extrahepatic portal vein. Patient 4 had epidermolysis bullosa. Patients 2 and 5
      had unremarkable recoveries, patients 2 and 3 had markedly delayed gastric
      emptying that responded to cisapride. Patient 3 has portal hypertension and
      remains under close follow-up. Patient 4 died at 22 days of age of pseudomonas
      sepsis. CONCLUSIONS: Based on our cases and literature review, we have adopted
      the following guidelines: (1) All children with pyloric atresia should be
      screened for multiple anomalies. (2) Delayed gastric emptying should be
      considered early and may respond to prokinetic agents. (3) Association with
      Epidermolysis bullosa should not preclude surgical treatment. (4) A skin biopsy
      specimen should be taken at the time of surgery for electron microscopy if there
      is a family history of epidermolysis bullosa.

PMID- 10945704
TI  - Inflammatory polyps after necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in
      the neonatal period. NEC causes ulceration of the intestinal mucosa and may lead
      to perforation or a stricture. To the best of the authors' knowledge intestinal
      inflammatory polyps after NEC have not been described previously. The authors
      report on a 17-week-old boy with pseudopolyps at the site of a colonic stricture
      after NEC.

PMID- 10945705
TI  - Conservative management of bilateral asynchronous adnexal torsion with necrosis
      in a prepubescent girl.
AB  - Conservative management of ovarian torsion consisting of detorsion and surgical
      stabilization of the involved ovary, and possibly including the uninvolved ovary,
      has been described in the adult population. A 6-year-old girl with a history of
      prior ovarian torsion resulting in oophorectomy presented with 72 hours of
      intermittent abdominal pain, anorexia, and 1 episode of vomiting. The patient had
      torsion of her remaining ovary diagnosed surgically and was managed with
      detorsion and oophoropexy, despite the severely necrotic appearance of the
      ovarian tissue. Postoperative serial ultrasound scans confirmed the viability and
      position of the ovary. In the prepubertal girl, ovaries may torse despite the
      absence of enlarging lesions such as tumors or cysts. To maximize the potential
      success of conservative therapy, torsion always must be included in the
      differential diagnosis of abdominal pain. Surgical management should attempt to
      salvage the torsed ovary, despite possible necrotic appearance, and also consider
      interventions to prevent recurrence, because bilateral torsion is a rare but
      potentially devastating complication.

PMID- 10945706
TI  - Congenital cysts of the third and fourth pharyngeal pouches or pyriform sinus
      cysts.
AB  - Cysts arising from the III and IV pharyngeal pouches, although uncommon, are
      typical in their presentation. They occur in neonates, invariably in the left
      anterior neck and cause respiratory distress. Excision of the cyst with ligation
      of the tract at the level of the pyriform sinus is curative.

PMID- 10945707
TI  - Xanthogranulomatous pyelonephritis presenting as a pseudotumor in a 2-month-old
      boy.
AB  - The authors report on a 2-month-old boy presenting with a right renal mass.
      Investigations including ultrasound scan and computed tomogram were suggestive of
      a renal tumor. A right nephrectomy was performed with great difficulty because of
      dense adhesions to the adjacent structures. Cut section of the specimen showed
      the entire kidney to be replaced by cheesy-yellow areas. Histological examination
      was suggestive of xanthogranulomatous pyelonephritis. Although rare at this age,
      xanthogranulomatous pyelonephritis should be considered in the differential
      diagnosis of a renal mass in children. The lesion is unique among the
      inflammatory conditions in closely mimicking renal tumours clinically. A thorough
      histological examination also is suggested because the features can get confused
      easily with those of renal tumors.

PMID- 10945708
TI  - Choledochal cyst associated with duodenal obstruction.
AB  - The association between congenital duodenal obstruction and concomitant
      choledochal cyst has not been reported, although duodenal obstruction is known to
      be associated with many other anomalies. The authors describe 2 patients with
      choledochal cyst with duodenal obstruction. In 1 patient, a diverticulum type of
      choledochal cyst was found within an annular pancreas. Cyst excision,
      choledochojejunostomy, and side-to-side duodeno-duodenostomy were performed. The
      other patient showed separated duodenal atresia and other multiple anomalies
      including imperforate anus. A choledochal cyst was noted at the time of duodeno
      duodenostomy and sigmoid colostomy. Cyst-enterostomy was performed at the age of
      8 months, but the patient died of multiple anomalies. Intraoperative
      cholangiography indicated an anomalous pancreatobiliary ductal junction (APBDJ).
      In both patients the bile in the cyst contained high levels of amylase,
      suggesting the presence of an APBDJ. An APBDJ is considered to play an etiologic
      role in the development of the choledochal cysts associated with duodenal
      obstruction.

PMID- 10945709
TI  - Unusual presentation of tuberculosis reactivation in childhood: an anterior neck
      mass.
AB  - Although extrapulmonary tuberculosis has a broad spectrum of clinical
      manifestations, involvement of the thyroid gland in children has been reported
      very rarely. The authors report a case of an 11-year-old girl with a nontender
      nodular swelling of the thyroid, whose symptoms, tomographic and scintigraphic
      features, mimicked a nodule with a cystic component. Although seldom observed,
      tuberculosis should be considered in the differential diagnosis of nodular
      lesions of the thyroid in children, especially in the patient with known history
      of exposure to tuberculosis.

PMID- 10945710
TI  - Laparoscopic repair of Morgagni-Larrey hernia in a child.
AB  - Primary laparoscopic repair of Morgagni-Larrey hernia has been described in adult
      patients but not in children. This is the first report of primary laparoscopic
      correction in the pediatric age group without using a prosthesis. A Morgagni
      Larrey hernia was found incidentally in a 3-year-old-girl. Laparoscopic
      correction of the defect was performed. After 6 months the patient is doing well.
      The chest radiograph shows complete resolution of the hernia. The laparoscopic
      approach allowed repair the hernia with minimal invasiveness. Laparoscopic
      correction is not difficult except for those hernias in which dense adhesions are
      present.

PMID- 10945711
TI  - Beckwith-Wiedemann syndrome and virilizing cortical adrenal tumor in a child.
AB  - The authors report a case of a virilizing adrenal tumor that developed in a 2
      year-old child with Beckwith-Wiedemann syndrome (BWS). He had a fetal diagnosis
      of omphalocele and a history of neonatal adrenal cysts. The importance of
      prenatal diagnosis of BWS and postnatal follow-up of tumors is discussed. The
      differential diagnosis of adrenal pathologies occurring in BWS also is reviewed.

PMID- 10945712
TI  - The otolaryngologic manifestations of gastroesophageal reflux: when is a pH sudy
      indicated?

PMID- 10945713
TI  - Spinal and sacral intervertebral continuous epidural anesthesia for transanal one
      stage Soave procedure for infants with Hirschsprung's disease.

PMID- 10945714
TI  - Lipid-lowering drug therapy: more knowledge leads to more problems for composers
      of guidelines.

PMID- 10945715
TI  - Cost-effectiveness of statins.
AB  - The efficacy of lipid-lowering with statins has become clear. Indirect
      estimations, and direct measurements from long-term randomized trials have also
      demonstrated cost-effectiveness, both in secondary and primary prevention of
      coronary heart disease. Targeting care efficiently to high-risk groups by
      calculating absolute risk is essential. However, it is clear that what would
      normally be very cost-effective interventions will put substantial strain on
      health care resources because of the common nature of coronary disease and risk
      factors.

PMID- 10945716
TI  - Debate: at what level of coronary heart disease risk should a statin be
      prescribed?
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are
      effective treatments for the primary and secondary prevention of coronary heart
      disease, but an outstanding issue is determining who should have such treatment.
      The benefit from treatment with statins appears to be proportional to the
      underlying risk of coronary heart disease and independent of the factors
      increasing risk. Most benefit will therefore be achieved by treating people at
      increased risk of coronary heart disease. Statins reduce coronary morbidity even
      when the risk of coronary heart disease is relatively low (6% over 10 years), but
      reduction in all-cause mortality, the true measure of safety has been shown only
      when the risk of a major coronary heart disease event is 15% over 10 years or
      greater. At this level of risk patients appear willing to take treatment to gain
      the benefit expected from statin treatment, and the cost effectiveness of statin
      treatment is within the range accepted for other treatments. The major
      impediments to the systematic introduction of statin treatment at this level of
      risk are the very high overall cost and the large workload in countries like
      Britain, where the population risk of coronary heart disease is high. For this
      reason, recent British guidelines correctly advise statin treatment for secondary
      prevention and primary prevention when the 10 year coronary heart disease risk is
      30% or greater as the first priority, moving to a lower coronary heart disease
      threshold for primary prevention only when resources permit.

PMID- 10945717
TI  - At what level of coronary heart disease risk should a statin be prescribed?
AB  - Statin therapy has been conclusively shown to offer patients clinical benefit,
      virtually irrespective of their baseline risk status. However, the absolute risk
      reductions observed in different clinical trials, which have recruited patients
      across a spectrum of lipid levels and vascular disease states, show that baseline
      global risk determines the absolute benefit gained and in turn will specify the
      number of patients needed to be treated in order to realize this benefit. Global
      risk assessment is therefore central to the clinically meaningful use of statin
      therapy, and a strong case is now argued in the literature for a high-risk
      primary prevention strategy that goes hand in hand with standard secondary
      prevention. The routine use of Framingham-based risk assessment tools is
      advocated because these are the most widely evaluated and have been repeatedly
      shown to predict the risk of coronary heart disease accurately in western
      populations. The risk threshold in primary prevention that should determine
      pharmacological intervention is the subject of controversy. The currently used
      annual risk figure of 3% would clearly capture all very high-risk individuals but
      would also deny treatment to many individuals who will subsequently die from
      their first coronary event. Although a 1.5% annual risk threshold is economically
      untenable in the present UK health system, a level of 2% is, we believe, both
      achievable and affordable.

PMID- 10945718
TI  - Management of dyslipidemia after coronary artery bypass grafting.
AB  - The results of serial angiographic studies and intervention trials in patients
      after coronary artery bypass artery grafting have provided ample evidence that
      abnormalities of the plasma lipoprotein system are one of the most significant
      risk factors for a rapid atherosclerotic attrition of saphenous vein grafts. In
      addition to confirming the well recognized role and contribution of cholesterol
      rich LDL or lipoprotein B particles to the progression of atherosclerotic
      lesions, intervention trials have also provided strong evidence for the
      atherogenic capacity of some intact and partly delipidized triglyceride-rich very
      low density lipoprotein and intermediate density lipoprotein (lipoprotein B
      complex) particles, and the protective effect of some (high density lipoprotein
      3) but not all high density lipoprotein particles. Most importantly, those
      studies have emphasized the need for an early, aggressive treatment of
      dyslipoproteinemias with pharmacological agents as the most efficient therapeutic
      approach to delaying, if not preventing, the detrimental effect of
      atherosclerosis on saphenous vein grafts.

PMID- 10945719
TI  - Serum triglycerides, the liver and the pancreas.
AB  - Massive hypertriglyceridaemia associated with fatty liver and abdominal pain or
      frank pancreatitis (the chylomicronaemia syndrome) is uncommon, but clinically
      important and under-recognized. It may arise as a result of severe genetic
      defects in lipolysis or, more commonly, from a moderate primary
      hypertriglyceridaemia that is exacerbated by a secondary cause. The latter
      include several drugs, among which the protease inhibitors, used for the
      treatment of human immunodeficiency virus infection, are increasingly apparent.
      In the acute situation plasma exchange, fat-free parenteral nutrition and acute
      insulin treatment, even in nondiabetic persons, may be valuable. A potentially
      major advance in prophylaxis is the use of high-dose antioxidant therapy, which
      has been shown to reduce attacks of pancreatitis even in the absence of a
      reduction in serum triglycerides. Asymptomatic patients with abnormal liver
      function tests are common in the lipid clinic, and can be a difficult group in
      which to make management decisions. Among those who are not taking excessive
      amounts of alcohol, many will have nonalcoholic steatohepatitis. The care of
      these patients is discussed, but there remains considerable uncertainty regarding
      their optimum management and prognosis.

PMID- 10945720
TI  - How high-density lipoprotein protects against the effects of lipid peroxidation.
AB  - The protective effect of HDL against the development of atherosclerosis appears
      to be multifaceted involving a number of mechanisms. One of the major mechanisms
      is, however, the ability of HDL to decrease, directly or indirectly, the lipid
      peroxidation of LDL. The hydrolysis of lipid peroxides by PON1 makes a major
      contribution to this effect of HDL. Evidence is accumulating that the PON1
      activity of human serum can be modulated by a variety of natural compounds and
      that these may increase or decrease the protective ability of PON1 and therefore
      of HDL on which it is exclusively located. Modulations of PON1 that enhance its
      activity may help to delay the atherosclerotic process.

PMID- 10945721
TI  - Cholesteryl ester transfer protein and atherosclerosis.
AB  - Plasma cholesteryl ester transfer protein facilitates the transfer of cholesteryl
      ester from HDL to apolipoprotein B-containing lipoproteins. Its significance in
      atherosclerosis has been debated in studies of human population genetics and
      transgenic mice. The current review will focus on human plasma cholesteryl ester
      transfer protein research, including TaqIB, 1405V, and D442G polymorphisms.
      Plasma cholesteryl ester transfer protein has a dual effect on atherosclerosis,
      depending on the metabolic background. In hypercholesterolaemia or combined
      hyperlipidaemia, plasma cholesteryl ester transfer protein may be pro-atherogenic
      and could be a therapeutic target.

PMID- 10945722
TI  - Thiazolidinediones, dyslipidaemia and insulin resistance syndrome.
AB  - Insulin resistance is known to unite several metabolic abnormalities. The
      associated dyslipidaemia appears to play a central role in this atherogenic
      syndrome. Thiazolidinediones, which are recently introduced insulin sensitizing
      agents, have been shown to be effective not only in reducing elevated glucose
      levels, but also in improving the other metabolic abnormalities that are
      associated with insulin resistance. The present review focuses on these potential
      effects of thiazolidinediones.

PMID- 10945723
TI  - Bibliography. Current world literature. Hyperlipidaemia and cardiovascular
      disease.

PMID- 10945724
TI  - Bimonthly update. Nutrition and metabolism.

PMID- 10945725
TI  - Bimonthly update. Genetics and molecular biology.

PMID- 10945726
TI  - Bimonthly update. Lipid metabolism.

PMID- 10945728
TI  - Bimonthly update. Atherosclerosis: cell biology and lipoproteins.

PMID- 10945727
TI  - Bimonthly update. Hyperlipidaemia and cardiovascular disease.

PMID- 10945729
TI  - Bimonthly update. Therapy and clinical trials.

PMID- 10945731
TI  - Ultrastructural study of meronts and gamonts of Choleoeimeria rochalimai
      (Apicomplexa: Eimeriidae) developing in the gall bladder of the gecko
      Hemidactylus mabouia from Brazil.
AB  - Endogenous development of Choleoeimeria rochalimai (Carini et Pinto, 1926)
      Lainson et Paperna, 1999 in the gall bladder of Hemidactylus mabouia (Moreau de
      Jonnes, 1818) from Belem, Brazil is reported at the fine structural level.
      Meronts and gamonts develop in the epithelial cells of the gall bladder. Infected
      cells become enlarged and displaced above the epithelial layer. Developing
      merozoites, dividing meronts and succession of developing microgamonts from
      initial nuclear division up to final microgamete differentiation are described.
      In addition towall forming bodies, mature macrogamonts possess a large inclusion
      or cisterna with fine granular contents.

PMID- 10945730
TI  - Trichodinid ciliates (Peritrichia: Trichodinidae) from the Bay of Kiel, with
      description of Trichodina claviformis sp. n.
AB  - Investigations on the epizoic fauna of Gadus morhua (L.), Platichthys flesus (L.)
      and Oncorhynchus mykiss (Walbaum) from the Kiel Fjord and Kiel Bight were carried
      out from September 1996 to March 1997. Smears from 120 G. morhua and 92 P. flesus
      caught using fish traps and trammel nets, and of 35 O. mykiss obtained from a
      local fish farm in the Kiel Fjord revealed the presence of three species of
      trichodinid ciliates, Trichodina claviformiis sp. n., Trichodina jadranica
      Haider, 1964 and Trichodina raabei Lom, 1962. The new species can be
      distinguished from other trichodinids by its large size in combination with the
      characteristically shaped adhesive disc containing denticles with club-like
      formed thorns. The thorns are directed anteriorly and not towards the centre of
      the adhesive disc. As the Kiel Bight and Kiel Fjord are new locality records for
      T. jadranica and T. raabei, morphological data are provided for both species.
      Trichodina claviformis is the first record of a peritrichous mobiline ciliate
      from Atlantic cod of the Baltic Sea. An identification key for 16 Trichodina
      species occurring on Baltic Sea fishes is provided based on the morphology of the
      adhesive disc and other well-established features. The occurrence of trichodinid
      ciliates on G. morhua and P. flesus in the Baltic Sea is discussed, especially
      considering the biology of the host and a possible host specificity of the
      species.

PMID- 10945732
TI  - Eimeria burdai sp. n. (Apicomplexa: Eimeriidae), a new parasite species from
      subterranean African silvery mole-rat, Heliophobius argenteocinereus.
AB  - A new coccidian parasite of the genus Eimeria Schneider, 1875 is described from
      the subterranean African silvery mole-rat Heliophobius argenteocinereus Peters,
      1846. Oocysts of Eimeria burdai sp. n. were subspherical to broadly ellipsoidal
      17.8 (16-19) x 14.1 (12-15), with a shape index 1.2 (1.1-1.4). Oocyst wall was
      bilayered, smooth and colourless, approximately 1.0 thick. Outer layer was
      significantly thicker than inner one. A micropyle and oocyst residuum were
      absent. One or two ellipsoidal or spherical polar granules were present.
      Sporocysts were ellipsoidal, 10.8 (9-12) x 6.2 (5-8) with a shape index 1.7 (1.5
      1.9). Sporocyst wall was single-layered, thin, smooth and colourless, with small
      Stieda body at the pointed end. In freshly sporulated oocysts, spherical
      sporocyst residuum was composed of small granules enclosed by a thin membrane.
      Sporozoites were elongate, lying length-wise in the long axis of the sporocyst,
      partially curled around each other, with single large refractile body located
      posteriorly. Faintly distinguishable nucleus was in the central part of the
      sporozoite. This eimerian represents the first coccidian species described from
      subterranean African silvery mole-rat (Rodentia: Bathyergidae).

PMID- 10945733
TI  - Heliocotyle ewingi sp. n. (Monogenea: Monocotylidae) from the gills of Myliobatis
      australis (Myliobatididae) from Tasmania, Australia.
AB  - Heliocotyle ewingi sp. n. (Monogenea: Monocotylidae) is described from the gills
      of Myliobatis australis Macleay, 1881 (Myliobatididae) collected from Norfolk Bay
      near Hobart, Tasmania, Australia. Heliocotyle ewingi can be distinguished readily
      from the only other species in the genus, Heliocotyle kartasi Neifar, Euzet et
      Ben Hassine, 1999, by the presence of a single pseudoseptum on each of the
      peripheral loculi except the posteriormost, eyespots and by the morphology of the
      male copulatory organ which is a short, straight sclerotised tube which lacks a
      sclerotised accessory piece. The generic diagnosis is revised to accommodate the
      new species and the anterior glands are discussed.

PMID- 10945734
TI  - Neotropical Monogenoidea 37. Redescription of Gyrodactylus superbus (Szidat,
      1973) comb. n. and description of two new species of Gyrodactylus
      (Gyrodactylidea: Gyrodactylidae) from Corydoras paleatus and C. ehrhardti
      (Teleostei: Siluriformes: Callichthyidae) of Southern Brazil.
AB  - Two new species of Gyrodactylus (Gyrodactylidae) are described from Corydoras
      paleatus (Jenyns) and Corydoras ehrhardti Steindachner (Callichthyidae) of Rio
      Piraquara, Municipality of Piraquara, near Curitiba, Parana, Brazil: Gyrodactylus
      anisopharynx sp. n. and Gyrodactylus samirae sp. n. These species are unique
      among the known Neotropical species of Gyrodactylus by the combination of several
      characters. Gyrodactylus anisopharynx is characterised by having hooks with point
      evenly curved, toe moderately pointed, round convex heel, straight sloping shelf,
      superficial bar with anterolateral projections and male copulatory organ armed
      with two rows of spinelets. Two variants of G. anisopharynx, of distinct pharynx
      size, are recognised: forma "large-pharynx" and forma "small-pharynx".
      Gyrodactylus samirae is characterised by having hook with straight shaft, short
      slightly recurved point, truncate toe, trapezoidal heel, shelf slightly concave,
      orthogonal to shaft; anchors with relatively short superficial root; superficial
      bar with extremities lightly expanded; and male copulatory organ armed with two
      rows of spinelets. Paragyrodactyloides superbus (Szidat, 1973) is redescribed and
      transferred to Gyrodactylus based on examination of type and new specimens.
      Features previously considered as diagnostic for the genus are misinterpretations
      or primitive characters for Gyrodactylus spp.

PMID- 10945735
TI  - Four species of digeneans, including Allocreadium patagonicum sp. n.
      (Allocreadiidae), from freshwater fishes of Patagonia, Argentina.
AB  - Four species of adult digeneans are reported from freshwater fishes of two lakes
      in Neuquen, Patagonia, Argentina. Allocreadium patagonicum sp. n.
      (Allocreadiidae) is described from the intestine of Percichthys colhuapiensis
      MacDonagh and Percichthys trucha (Cuvier et Valenciennes) (Percichthyidae) from
      Lago Alumine. Three species redescribed are: Acanthostomoides apophalliformis
      Szidat, 1956 (Acanthostomidae) from the intestine of P. colhuapiensis and P.
      trucha from Lago Alumine and of Salmo trutta (Linnaeus) (Salmonidae) from Lago
      Huechulafquen; Deropegus patagonicus (Szidat, 1956) comb. n. (= Genarches
      patagonicus Szidat, 1956) (Derogenidae) from the stomach of P. colhuapiensis, P.
      trucha, Oncorhynchus mykiss (Walbaum) (Salmonidae) and Salvelinus fontinalis
      (Mitchill) (Salmonidae) from Lago Alumine and of S. trutta from Lago
      Huechulafquen; and Austrocreadium papilliferum Szidat, 1956 from the intestine of
      P. trucha from Lago Alumine. The genus Polylekithum Arnold, 1934 is considered a
      synonym of the genus Allocreadium Looss, 1900. The genus Austrocreadium Szidat,
      1956 is removed to the family Homalometridae.

PMID- 10945736
TI  - Host-parasite relationships of Zootoca vivipara (Sauria: Lacertidae) in the
      Pyrenees (North Spain).
AB  - The helminths infesting the common lizard, Zootoca vivipara (Jacquin, 1787), were
      studied with special attention to the relations between the number of nematodes,
      Oswaldocruzia filiformis (Goeze, 1782), and the size, sex and age class of the
      host. The possible seasonality of the parasite intensity and the relationship
      with the feeding habits of the host were also tested. Helminth infracommunities
      of Z. vivipara were depauperate with lizards harbouring only two species, the
      trematode Plagiorchis molini (Lent et Freitas, 1940) and the nematode O.
      filiformis. A positive correlation between host size and the number of O.
      filiformis was found for female Z. vivipara. However, no correlation was detected
      between intensity and sex or age class. The feeding habits of Z. vivipara, the
      isolation of the population studied and the low level of interaction with other
      reptilian or amphibian species are suggested as the causes of the depauperate
      helminth infracommunities found in this lacertid lizard.

PMID- 10945737
TI  - Trypanorhynch cestodes from Indonesian coastal waters (East Indian Ocean).
AB  - Results of a study on trypanorhynch cestodes of fishes from Indonesian coastal
      waters are presented. A new species, Dasyrhynchus thomasi sp. n., is described,
      and five species are recorded which all represent new locality records:
      Tentacularia coryphaenae Bosc, 1797; Nybelinia africana Dollfus, 1960; Nybelinia
      scoliodoni (Vijayalakshmi, Vijayalakshmi et Gangadharam, 1996); Sphyriocephalus
      dollfusi Bussieras et Aldrin, 1968; and Otobothrium penetrans Linton, 1907. Their
      known ranges of distribution are extended to the East-Indian Ocean. Scanning and
      transmission electron microscopy was used to clarify details of the tentacular
      armature and surface morphology of T. coryphaenae, D. thomasi and O. penetrans.
      In T. coryphaenae, hook-like microtriches along the bothridial tegument are
      embedded in the distal cytoplasm, sometimes showing a split base. The solid
      tentacular hooks are embedded into a fibrillar, highly ordered tentacular wall.
      D. thomasi is distinguished by its characteristically shaped bothridia and a
      triple chainette with winged hooks on the external surface of the tentacle. Tufts
      of microtriches with ciliated sensory receptors are regularly arranged on the
      bothridial surface of O. penetrans. They show similarities to sensory receptors
      reported from other trypanorhynch cestodes. Otobothrium pephrikos Dollfus, 1969
      is considered a junior synonym for O. penetrans, and the variability of the
      scolex within trypanorhynch cestodes is emphasised.

PMID- 10945738
TI  - Hypobiosis induction alters the protein profile of Ostertagia ostertagi
      (Nematoda: Trichostrongylidae).
AB  - The appearance of variations in the protein profile of Ostertagia ostertagi
      (Stiles, 1892) infective larvae (L3), which were induced by hypobiosis triggering
      factors, was evaluated by means of SDS-PAGE and densitometric analysis. Area
      integration analyses of their protein profiles was carried out between 66 and 77
      kDa. Important quantitative variations were identified in the protein levels of
      the induced larvae, where a 5.25 fold increase compared to the control was
      observed. Two 75.4 and 70 kDa protein bands were found which exceeded the control
      profile by 4.5 and 44 fold, respectively. This fact suggests that the changes
      brought about in the process of hypobiosis induction are restricted. This work
      demonstrates changes at a molecular level corresponding with biological changes
      induced by conditions causing O. ostertagi hypobiosis.

PMID- 10945739
TI  - Proteolytic enzymes secreted by larval stage of the parasitic nematode
      Trichinella spiralis.
AB  - Excretory/secretory products (ES), collected from in vitro cultures of muscle
      larvae (L1) of Trichinella spiralis (Owen, 1835) were examined for the presence
      of proteolytic enzymes. Several discrete proteinases in the size range of 25-55
      kDa were identified by substrate gel electrophoresis and were characterised
      according to pH optima, substrate specificity and inhibitor sensitivity using
      azocasein assay. Serine, cysteine and metalloproteinases active at pH 5-7 were
      identified. The serine proteinases were found to predominate and some of them
      were found to be specific for the larval stage of the parasite. The results from
      the substrate analysis indicated the presence of collagenolytic and elastolytic
      activities. The proteinase activity was inhibited by IgG isolated from T.
      spiralis-infected mice, an observation of relevance to understanding
      host/parasite interactions and, ultimately, the development of anti-Trichinella
      vaccine.

PMID- 10945740
TI  - Peculiarities of behaviour of taiga (Ixodes persulcatus) and sheep (Ixodes
      ricinus) ticks (Acarina: Ixodidae) determined by different methods.
AB  - A comparison of the behavioural peculiarities of Ixodes persulcatus Schulze, 1930
      (north-western population, Russia) and Ixodes ricinus (L., 1758) from western
      Russia and Denmark was determined by using two methods. Method 1 involved a
      sojourn of ticks on vertical plastic sticks and showed that the questing
      behaviour of I. ricinus nymphs was dependent on temperature and relative humidity
      (RH). A significantly greater number of nymphs quested at 22 degrees C and 100%
      RH than at 18 degrees C. When the humidity was reduced to 30% all of the nymphs
      departed. In the second method, the activity of ticks on an inclined "ticksdrome"
      was estimated. The activity of I. ricinus adults from the Danish population was
      1.2 times greater than that of ticks from Russia. Females of the species studied
      and specimens from all study areas were more active than all other stages of
      development. The locomotor activity of both adult and immature I. ricinus that
      were infected with Borrelia burgdorferi sensu lato was suppressed when compared
      with uninfected specimens. The locomotor activity of I. persulcatus females
      infected by borreliae with exoskeleton anomalies was 1.3 times greater (P<0.05)
      than that of infected ticks without anomalies. Our data showed that infected
      females with exoskeleton anomalies could crawl faster on a human and reach
      uncovered parts of the body that are vulnerable for attachment and feeding. A
      study of locomotor activity and questing behaviour may be useful for comparing
      the risk for different tick species and populations to transmit tick-borne
      pathogens.

PMID- 10945741
TI  - Host-parasite interface between Asellus aquaticus (Isopoda) and larvae of
      Acanthocephalus anguillae (Acanthocephala).

PMID- 10945742
TI  - Autofluorescence in the oocysts of marine and freshwater fish coccidia.

PMID- 10945743
TI  - Differences between the sexes with regard to work-related skin disease.
AB  - Work-related skin disease is common and usually presents as hand eczema. From the
      Occupational Injury Information System in Sweden, as well as from registers of
      industrial injuries in other countries, it is evident that females report skin
      disease more often than males. Epidemiological studies of hand eczema also show
      that women are more often affected than men, in particular young women. The most
      common type of hand eczema is irritant contact dermatitis, which is often caused
      by wet work. Many female-dominated occupations involve extensive wet work, e.g.,
      hairdressing, catering, cleaning and health-care work. These occupations are also
      high-risk occupations for hand eczema. Experimental studies of skin irritation
      have not confirmed differences between the sexes; thus, the higher prevalence of
      irritant contact dermatitis among females is most likely due to exposure,
      occupational and non-occupational. Nickel allergy is the most common contact
      allergy, which is most frequent in young females, and in 30-40% results over time
      in hand eczema. Hand eczema has an impact on quality of life and females seem to
      report a higher degree of discomfort than males. To achieve the optimal effect of
      preventive efforts regarding occupational skin disease, the focus for prevention
      should aim at reducing wet exposure.

PMID- 10945744
TI  - Sensitizing capacity of 5,5'-di-tert-butyl-2,2'-dihydorxy-(hydroxymethyl)
      dibenzyl ethers in the guinea pig.
AB  - In patients hypersensitive to p-tert-butylphenol-formaldehyde resin (PTBP-F-R),
      it is for diagnostic, therapeutic and preventive reasons necessary to know the
      identity of the primary sensitizing substances, their sensitizing capacities as
      well as their cross-reaction patterns. We have recently shown that the 2 dimers
      in PTBP-F-R, 5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether (X)
      and 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether (IX)
      are contact sensitizers in man. The aim of this study was to investigate the
      sensitizing capacities of these dimers in PTBP-F-R and potential cross-reacting
      substances in the guinea pig with the guinea pig maximization test. IX, X, 2,6
      dimethylol-p-tert-butylphenol (2,6-MPTBP), 2-methylol-p-tert-butylphenol (2
      MPTBP), p-tert-butylcatechol (PTBC), 5,5'-di-tert-butyl-2,2'-dihydroxy-dibenzyl
      ether (XI) were used as possible cross reacting substances. IX and X were shown
      to be sensitizers. When compared to the sensitizers in phenol-formaldehyde resin,
      IX is a strong sensitizer (p= 0.00052) and X a moderate sensitizer (p=0.0053).
      Animals sensitized to IX showed cross-reactions to X (p=0.010), 2,6-MPTBP
      (p=0.0011) and PTBC (p=0.0498). Animals sensitized to X showed no cross-reactions
      to the substances that were tested. The results indicate that IX is a main
      allergen in PTBP-F-R, with possibly also X.

PMID- 10945745
TI  - Topical application of docosanol- or stearic acid-containing creams reduces
      severity of phenol burn wounds in mice.
AB  - Because of their reported antiviral and anti-inflammatory activities, cream
      formulations containing n-docosanol (docosanol) or stearic acid were tested for
      effects on chemically-induced burns in mice. In this model, injury was induced by
      painting the abdomens of mice with a chloroform solution of phenol. This was
      followed by the topical application of test substances 0.5, 3, and 6 h later.
      Progression of the wounds was assessed by a single evaluator after 8 h, using a
      numerical score of gross morphology. Docosanol- and stearic acid-containing
      creams substantially and reproducibly lessened the severity and progression of
      skin lesions compared to untreated sites with a 76% and 57% reduction in mean
      lesion scores, respectively. Untreated wounds appeared red and ulcerated;
      docosanol cream-treated wounds showed only slight erythema.

PMID- 10945746
TI  - Skin irritation from air-oxidized ethoxylated surfactants.
AB  - Surfactants are known to be skin irritants, but change in their irritant
      potential due to change in composition during handling and storage has not
      previously been investigated. The aim of this study was to investigate the
      influence of oxidation products on the irritant potential of a non-ionic
      ethoxylated alcohol, C12E5. Pure and oxidized C12E5 were tested, using 2
      different patch test procedures; 1 with a single 24 h exposure and 1 with
      repeated exposures. 18 healthy volunteers participated in each of these studies.
      Evaluations were made by visual scoring and by measurement of transepidermal
      water loss and skin blood flow. In the single exposure study, no significant
      difference in skin irritation was observed between pure C12E5 and a sample of
      oxidized C12E5 at the concentrations tested (1, 3, 9 and 27%). After repeated
      exposures, however, the oxidized C12E5 was significantly more irritant than pure
      C12E5 at the concentrations 9% and 27% (p<0.05). Non-ionic ethoxylated
      surfactants are known for their weak skin irritant effect and are, due to this,
      often included in products with prolonged contact with the skin, i.e., skin care
      products. An increased irritant potential after oxidation might be of importance
      due to the conditions of use.

PMID- 10945747
TI  - Patch testing and aeroallergen intradermal testing in facial dermatitis.
AB  - The role of contact allergens and aeroallergens in facial dermatitis (FD) was
      studied. 114 cases of FD were divided into 3 groups. Group 1 comprised 47 cases
      of facial cosmetic dermatitis (FCD), in which all patients had a history of
      dermatitis related to cosmetics clinically; group 2 comprised 15 cases of
      seasonal facial dermatitis (SFD); Group 3 comprised 52 cases of other FD (OFD)
      that could not be categorized as FCD or SFD. Reactions to contact allergens and
      aeroallergens were detected using patch testing and intradermal testing,
      respectively, with non-facial eczematous skin disease patients serving as
      controls. The positivity rate for each allergen between different groups was
      compared by the chi2-test. The results show that the positivity rate for
      fragrance mix in FCD is much higher than in non-FCD (27.7% versus 6.7% in SFD,
      7.6% in OFD and 6% in eczema patients, p<0.05). No significant difference was
      detected for other common allergens, such as PPD, rubber mix, nickel sulfate, and
      colophonium (p>0.05 for all). These results suggest that fragrance mix contains
      the main contact allergens in FCD. Patch testing with patients' own products also
      yields high numbers of relevant results in FCD and OFD. No relevant patch test
      results were found in SFD, indicating that contact allergy may not be relevant to
      SFD. No significant difference was observed between intradermal skin reactions to
      aeroallergens, including pollens and moulds, in SFD, OFD, FCD and controls. These
      results suggest that Type I reactions to aeroallergens may not be relevant in FD.
      The role of aeroallergens in FD needs to be studied further.

PMID- 10945749
TI  - Expression of metallothioneins-I and -II isoforms at positive patch-test sites.
AB  - The expression and the distribution of metallothioneins (MT)-I and II isoforms
      were evaluated in 5 healthy volunteers and in 16 subjects with positive patch
      test reactions to various compounds. Skin specimens taken both from the healthy
      skin of the back and at positive patch test sites (at 48 h), were treated using a
      3-step indirect immunoperoxidase procedure with a mouse monoclonal IgG1 antibody
      reactive against I and II isoforms of human, rat and horse MT. MT were expressed
      in the basal layer of the healthy skin of both controls and sensitive subjects,
      without any significant difference. At positive patch test sites, there was an
      overexpression of MT in basal and suprabasal layers of the epidermis.
      Overexpression of MT, related to the degree of the inflammatory reactions
      elicited by the penetrating compounds was observed in the dermis. The cells
      expressing MT in the dermis were mostly T lymphocytes and cells with dendritic
      morphology which positively stained in part for CD34 and in part for XIIIa
      markers and negatively for KP1, S100 and HLA-DR. Taken together, these results
      seem to indicate that MT represent a constitutive mechanism of defence expressed
      by different types of cells in the skin, which is triggered by contact with both
      metallic and non-metallic compounds. The biological significance of MT in the
      skin remains to be elucidated. Our preliminary findings do not permit evaluation
      of whether these nearly ubiquitous proteins exert their cytoprotective effects in
      the skin acting simultaneously as antioxidant, metal binding or zinc suppliers,
      or if they display these activities mainly depending on the nature of the
      penetrating substances.

PMID- 10945748
TI  - Activity of human contact allergens in the murine local lymph node assay.
AB  - The murine local lymph node assay (LLNA) is a predictive test for the
      identification of chemicals that have the potential to cause skin sensitization.
      Since its original development, the assay has been the subject of national and
      international evaluation studies and extensive comparisons with guinea pig tests
      and human data. On the basis of these investigations, the LLNA has recently been
      endorsed by ICCVAM (Interagency Coordinating Committee on the Validation of
      Alternative Methods) as a stand-alone method for skin sensitization hazard
      identification. At the same time, ICCVAM confirmed that, although the LLNA is not
      an in vitro method, it does represent a refinement in the way animals are used
      and can provide a means for reducing the number of animals used in sensitization
      hazard assessment. The investigations described here were designed to explore
      further the ability of the LLNA to identify accurately those chemicals that cause
      allergic contact dermatitis in humans. To that end we have measured, amongst 3
      independent laboratories, LLNA responses induced by a total of 18 test chemicals,
      11 of which are known to cause skin sensitization and 7 of which are believed not
      to be associated with any significant evidence of allergic contact dermatitis in
      humans. The LLNA correctly classified 16 of the 18 materials. The 11 chemicals
      tested which are associated with allergic contact dermatitis in humans were found
      to be positive in the LLNA. Of the 7 materials believed to be non-sensitizers, 5
      were negative in the LLNA and 2 produced positive results. Collectively, these
      data provide additional evidence that the LLNA is able to discriminate skin
      sensitizers from those chemicals which do not possess a significant skin
      sensitization potential and thus provides a method for hazard identification that
      offers important animal welfare benefits.

PMID- 10945751
TI  - Spill-induced sensitization to isophoronediamine.

PMID- 10945750
TI  - Increase in contact allergy to fragrances: patch-test results 1989-1998.
AB  - We report the results of patch tests with fragrance-mix as a part of the standard
      series carried out over the last 10 years (1989-1998) during routine testing of
      6129 patients in our department. 5.9% of the total number of patients who were
      patch tested were positive to fragrance mix. The sex ratio was 2.3:1 with a
      female predominance. In 1989-1993, the frequency of contact sensitivity to
      fragrance mix was 3.9% (4.9% for females and 2.1% for males). This rate rose both
      in female and male patients during the observed period of time and attained 8.9%
      (females) and 4.1% (males) in 1994-1998; the overall frequency in 1994-98 was
      7.5%. This rising trend, which was statistically significant, might be the
      consequence of an increased use of cosmetics and toiletries containing fragrances
      in our population.

PMID- 10945752
TI  - Occupational latex contact urticaria in non-health-care occupations.

PMID- 10945753
TI  - Contact allergy to oak moss resin in a soluble oil.

PMID- 10945754
TI  - Baboon syndrome of unusual origin.

PMID- 10945755
TI  - Occupational allergic contact dermatitis from trivalent chromium in leather
      tanning.

PMID- 10945756
TI  - Allergic contact reactions to poly(oxy-1,2-ethanediyl) alpha,alpha'-[(1
      methylethylidene)di-4, 1-phenylene]bis[omega-[(2-methyl-1-oxo-2-propenyl)oxy](BIS
      EMA) .

PMID- 10945757
TI  - Allergic contact dermatitis due to eucalyptol in an anti-inflammatory cream.

PMID- 10945758
TI  - Contact dermatitis from maleated soybean oil: last gasps of an expiring cosmetic
      allergen.

PMID- 10945759
TI  - Frullania dermatitis.

PMID- 10945760
TI  - Contact sensitivity to tetrahydroxypropyl ethylenediamine in a sunscreen, without
      cross-sensitivity to ethylenediamine.

PMID- 10945761
TI  - Occupational compound allergy to an industrial grease caused by an oxidation
      product of phenyl-alpha-naphthylamine.

PMID- 10945762
TI  - Transepidermal water loss (TEWL) measurements on the face.

PMID- 10945764
TI  - Immersion oil allergy with no reaction to epoxy resin in the standard series.

PMID- 10945763
TI  - Allergic contact dermatitis from pine tar.

PMID- 10945765
TI  - Triple transduction with adeno-associated virus vectors expressing tyrosine
      hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for
      gene therapy of Parkinson's disease.
AB  - Parkinson's disease (PD), a neurological disease suited to gene therapy, is
      biochemically characterized by a severe decrease in the dopamine content of the
      striatum. One current strategy for gene therapy of PD involves local production
      of dopamine in the striatum achieved by inducing the expression of enzymes
      involved in the biosynthetic pathway for dopamine. We previously showed that the
      coexpression of tyrosine hydroxylase (TH) and aromatic-L-amino-acid decarboxylase
      (AADC), using two separate adeno-associated virus (AAV) vectors, resulted in more
      effective dopamine production and more remarkable behavioral recovery in 6
      hydroxydopamine-lesioned parkinsonian rats, compared with the expression of TH
      alone. Not only levels of TH and AADC but also levels of tetrahydrobiopterin
      (BH4), a cofactor of TH, and GTP cyclohydrolase I (GCH), a rate-limiting enzymes
      for BH4 biosynthesis, are reduced in parkinsonian striatum. In the present study,
      we investigated whether transduction with separate AAV vectors expressing TH,
      AADC, and GCH was effective for gene therapy of PD. In vitro experiments showed
      that triple transduction with AAV-TH, AAV-AADC, and AAV-GCH resulted in greater
      dopamine production than double transduction with AAV-TH and AAV-AADC in 293
      cells. Furthermore, triple transduction enhanced BH4 and dopamine production in
      denervated striatum of parkinsonian rats and improved the rotational behavior of
      the rats more efficiently than did double transduction. Behavioral recovery
      persisted for at least 12 months after stereotaxic intrastriatal injection. These
      results suggest that GCH, in addition to TH and AADC, is important for effective
      gene therapy of PD.

PMID- 10945767
TI  - Nonviral glial cell-derived neurotrophic factor gene transfer enhances survival
      of cultured dopaminergic neurons and improves their function after
      transplantation in a rat model of Parkinson's disease.
AB  - Transplantation of dopaminergic fetal mesencephalic tissue into the striatum is
      currently being developed for treatment of patients with advanced Parkinson's
      disease. Ethical concerns regarding the use of human fetal tissue, and the
      limited availability as well as poor survival and differentiation of dopaminergic
      neurons after transplantation have reduced the extent and outcome of this
      approach so far. With the purpose of finding means to increase the yield of
      dopaminergic neurons in transplants, and to reduce the amount of fetal tissue
      needed for each transplanted patient, we transfected rat fetal ventral
      mesencephalic (VM) tissue grown as organotypic free-floating roller tube (FFRT)
      cultures with a vector encoding human glial cell-derived neurotrophic factor
      (hGDNF). For transfer of an episomal expression vector (pRep7-GDNF8) a nonviral,
      nonliposomal cationic transfection technique was applied and optimized.
      Recombinant hGDNF expression resulted in a higher number of TH-positive neurons
      in the cultures as measured 6 days after transfection. Ventral mesencephalic
      cultures expressing hGDNF were then grafted into the striatum of unilaterally 6
      hydroxydopamine (6-OHDA)-lesioned rats. Grafting of genetically modified VM
      cultures resulted in earlier functional recovery compared with grafting
      nontransfected cultures. We conclude that organotypic free-floating roller tube
      cultures can be successfully transfected to produce hGDNF with effects on TH
      expressing neurons in vitro and functional effects after grafting in a rat
      Parkinson's disease model.

PMID- 10945766
TI  - Ultrasound facilitates transduction of naked plasmid DNA into colon carcinoma
      cells in vitro and in vivo.
AB  - One approach to improve the efficacy of in vivo gene therapy, with the aim at
      enhancing expression of the transgene, involves utilization of mechanical forces
      to facilitate transduction of DNA into cells. In this study, we evaluated the
      feasibility of mechanical insonation in gene transfers with naked DNA plasmid
      loading both in vitro and in vivo. We used an ultrasound probe, which can focus
      the ultrasonic beam in the exit zone of the probe. The reporter pcDNA3-lacZ
      plasmid, containing Escherichia coli lacZ or the beta-galactosidase gene (beta
      gal), and the neomycin 3'-phosphotransferase gene (neo), was used for evaluation
      of transfer efficiency. Expression of beta-gal in MC38 murine colon carcinoma
      cells was measured after insonation of 20 W/cm2 with continuous 1.0-MHz wave
      exposure. In a transient assay, significant numbers of cells were transduced with
      the beta-galactosidase gene. After cells were treated with geneticin, we also
      observed a difference in colonogenicity between noninsonated and insonated
      groups. When MC38 cells were implanted in syngeneic mice and plasmid was
      injected, the insonation that followed facilitated beta-galactosidase expression.
      These results indicate that insonation represents a potential approach for gene
      therapy when combined with naked DNA plasmid injection.

PMID- 10945768
TI  - Expression of glucokinase in skeletal muscle: a new approach to counteract
      diabetic hyperglycemia.
AB  - Chronic hyperglycemia is responsible for diabetes-specific microvascular and
      macrovascular complications. To reduce hyperglycemia, key tissues may be
      engineered to take up glucose. To determine whether an increase in skeletal
      muscle glucose phosphorylation leads to increased glucose uptake and to
      normalization of diabetic alterations, the liver enzyme glucokinase (GK) was
      expressed in muscle of transgenic mice. GK has a high Km for glucose and its
      activity is not inhibited by glucose 6-phosphate. The presence of GK activity in
      skeletal muscle resulted in increased concentrations of glucose 6-phosphate and
      glycogen. These mice showed lower glycemia and insulinemia, increased serum
      lactate levels, and higher blood glucose disposal after an intraperitoneal
      glucose tolerance test. Furthermore, transgenic mice were more sensitive to
      injection of low doses of insulin, which led to increased blood glucose disposal.
      In addition, streptozotocin (STZ)-treated transgenic mice showed lower levels of
      blood glucose than STZ-treated controls and maintained body weight. Moreover,
      injection of insulin to STZ-treated transgenic mice led to normoglycemia, while
      STZ-treated control mice remained highly hyperglycemic. Thus, these results are
      consistent with a key role of glucose phosphorylation in regulating glucose
      metabolism in skeletal muscle. Furthermore, this study suggests that engineering
      skeletal muscle to express GK may be a new approach to the therapy of diabetes
      mellitus.

PMID- 10945769
TI  - Pre-existent adenovirus antibody inhibits systemic toxicity and antitumor
      activity of CN706 in the nude mouse LNCaP xenograft model: implications and
      proposals for human therapy.
AB  - Pre-existent humoral antibody to adenovirus potentially confounds human clinical
      trials involving intravascular administration of adenovirus. Using the LNCaP
      prostate cancer xenograft model in BALB/c nu/nu mice and the prostate-specific
      attenuated replication-competent adenovirus (ARCATM) CN706, we developed an
      animal model that systematically controls both the dose of intravascularly
      administered adenovirus and the titer of the pre-existent anti-Ad5 antibody, and
      then measures the virus-induced toxicity as well as antitumor activity. We
      prepared hyperimmune sera to adenovirus in rabbits, passively injected the
      purified rabbit anti-Ad5 antibody into tumor-bearing mice, and established
      measurable humoral anti-Ad5 antibody titers. CN706 was intravenously injected
      into the tail vein of animals 24 hr after passive anti-Ad5 antibody
      administration. In the absence of pre-existent antibody, the lethal dose (LD100)
      for BALB/c nu/nu mice was 2.5x10(11) CN706 particles, whereas 1x10(11) CN706
      particles was not lethal. However, in the presence of a 1:80 pre-existent titer
      of Ad5 neutralizing antibody (NAb), intravenous injection of 5x10(11) CN706
      particles was no longer lethal. In addition, pre-existent antibody also prevented
      antitumor activity in a dose-dependent manner: 1x 10(11) CN706 particles
      prevented LNCaP xenograft tumor progression, but antitumor activity was
      eliminated by a pre-existent 1:80 NAb titer. These results led us to propose
      transient removal of pre-existent adenovirus antibody by immunoapheresis. An
      affinity column of cloned virus capsid proteins was constructed that was able to
      specifically remove adenovirus antibody from human clinical serum samples. A 5
      min disposable immunoassay was also developed to monitor the level of pre
      existent antibody in sera before and after immunoapheresis. Clinically, this
      approach may enable controlled clinical studies of intravenously administered
      adenovirus in patients with pre-existent anti-adenovirus antibody.

PMID- 10945770
TI  - Enhanced ganciclovir killing and bystander effect of human tumor cells transduced
      with a retroviral vector carrying a herpes simplex virus thymidine kinase gene
      mutant.
AB  - Gene transfer of the herpes simplex virus thymidine kinase (TK) gene associated
      with ganciclovir (GCV) treatment can lead to death of TK-expressing cells, and of
      neighboring TK- cells because of the bystander effect. Thus, a small proportion
      of TK+ cells in a tumor can lead to its complete regression after GCV treatment.
      However, a lack of efficacy of gene transfer into tumors associated with low GCV
      sensitivity and poor bystander effect of human cancer cells currently limit the
      clinical use of this suicide gene therapy approach. To increase the potency of
      suicide gene therapy, we have tested the GCV sensitivity and the bystander effect
      of TK mutants that have been previously described. After retroviral transduction
      of the TK mutants into human tumor cells of various origins, we have found a
      strong killing effect of GCV with cells expressing the mutants TK30 or TKF161C.
      The GCV sensitivity of several human tumor cell types expressing TK30 was 9- to
      500-fold higher than cells containing wild-type TK. Furthermore, TK30-expressing
      cells were able to kill bystander cells much more efficiently than TK-expressing
      cells. Thus, TK30 mutant is a promising candidate for suicide gene therapy
      clinical trials.

PMID- 10945771
TI  - Transduction of CD34+ cells from the bone marrow of HIV-1-infected children:
      comparative marking by an RRE decoy gene and a neutral gene.

PMID- 10945772
TI  - Detection of cryptosporidia and Cryptosporidium parvum oocysts in environmental
      water samples by immunomagnetic separation-polymerase chain reaction.
AB  - Cryptosporidium parvum has emerged as one of the most important new contaminants
      found in drinking water. Current protocols for the detection of cryptosporidia
      are time-consuming and rather inefficient. We recently described an
      immunomagnetic separation-polymerase chain reaction (IMS-PCR) assay permitting
      highly sensitive detection of C. parvum oocysts in drinking water samples. In
      this study, a second IMS-PCR assay to detect all cryptosporidial oocysts was
      developed, and both IMS-PCR assays were optimized on river water samples. A
      comparative study of the two IMS-PCR assays and the classical detection method
      based on an immunofluorescence assay (IFA) was carried out on 50 environmental
      samples. Whatever the type of water sample, the discrepancy in C. parvum
      detection between the IFA and IMS-PCR took the form of IFA-negative/IMS-PCR
      positive results, and was caused mainly by the greater sensitivity of IMS-PCR as
      compared with IFA. Of the 50 water samples, only five tested positive for C.
      parvum using IMS-PCR, and could constitute a threat to human health. These
      results show that both IMS-PCR assays provide a rapid (1 d) and sensitive means
      of screening environmental water samples for the presence of cryptosporidia and
      C. parvum oocysts.

PMID- 10945773
TI  - The detection of astrovirus in sludge biosolids using an integrated cell culture
      nested PCR technique.
AB  - The work presented here demonstrates the utility of the integrated cell culture
      reverse transcriptase-polymerase chain reaction (ICC-RT-PCR) coupled with nested
      PCR to detect human astroviruses and enteroviruses in sludge biosolids. Viruses
      were concentrated by beef extract elution and organic flocculation prior to
      analysis by a plaque assay and ICC-RT-PCR. Astroviruses were detected in all but
      one sample and all of the samples were positive for enteroviruses. We have
      demonstrated the prevalence and frequency ofastrovirus in sludge and validated
      the ICC-RT-PCR/nested PCR technique as a useful tool to detect viruses in sludge.

PMID- 10945774
TI  - In vitro cytotoxicity of non-cyt inclusion proteins of a Bacillus thuringiensis
      isolate against human cells, including cancer cells.
AB  - A soil isolate designated 90-F-45-14, belonging to Bacillus thuringiensis serovar
      dakota (H15), was examined for characterization of in vitro cytotoxicity,
      associated with parasporal inclusion proteins, against human cells. When
      activated with proteolytic processing, inclusion proteins of the isolate 90-F-45
      14 exhibited a moderate cytotoxicity against the human uterus cervix cancer cells
      (HeLa) with an EC(50) value of 60.8 microg ml(-1), while showing extremely high
      activities on the human leukaemic T cells (MOLT-4) and the normal T cells with
      EC(50) values of 0.27 and 0.20 microg ml(-1), respectively. Anti-leukaemic cell
      activity of the 90-F-45-14 proteins was eight to nine times greater than that of
      the B. thuringiensis serovar israelensis proteins containing the Cyt1 protein, a
      broad-spectrum cytolysin. The cytopathy by the 90-F-45-14 proteins was
      characterized by marked cell-ballooning, while the israelensis proteins induced
      early breakdown of the cells due to cytolysis. Inclusions of the isolate
      consisted of five major polypeptides of 170, 103, 73, 40 and 32 kDa. A 100%
      homology was observed in the sequence of 15 N-terminal amino acids between the
      proteins of 170 and 103 kDa. There was no N-terminal sequence homology between 90
      F-45-14 proteins and the existing Cry/Cyt proteins of B. thuringiensis.
      Proteolytic processing by proteinase K yielded several proteins with molecular
      masses ranging from 40 to 28 kDa.

PMID- 10945775
TI  - Yeast communities and genetic polymorphism of Saccharomyces cerevisiae strains
      associated with artisanal fermentation in Brazil.
AB  - Yeast communities and genetic polymorphism of prevalent Saccharomyces cerevisiae
      strains isolated from the spontaneous fermentation of the sugarcane juice during
      the production of aguardente in three distilleries in the state of Minas Gerais,
      Brazil, were studied. S. cerevisiae was the prevalent species during the process
      of aguardente production, but Schizosaccharomyces pombe was predominant in old
      fermentations in one distillery. Transient yeast species were found in a variable
      number, probably due to the daily addition of sugarcane juice, and they were
      different for each of the three distilleries studied. PFGE and PCR analysis of
      the predominant strains of S. cerevisiae isolated from the fermented must showed
      a high degree of genetic polymorphism among the three distilleries. A high
      molecular variability of S. cerevisae strains was also observed among strains
      isolated from the same vat at different fermentation ages. Our results showed
      that there was a succession of geneticly different strains of S. cerevisae during
      the process of aguardente production.

PMID- 10945776
TI  - Microemulsions are membrane-active, antimicrobial, self-preserving systems.
AB  - Microemulsions are physically stable oil/water systems that have potential use as
      delivery systems for many pharmaceuticals which are normally of limited use due
      to their hydrophobicity, toxicity or inability to access the site of action. It
      has been suggested that microemulsions are self-preserving antimicrobials in
      their own right, although there is little evidence to support this. In this
      experiment, microemulsions of various compositions were formulated and tested for
      their stability and antimicrobial action. The physical stability of the different
      microemulsions was assessed by centrifugation at 4000g and by storage in a water
      bath at 37 degrees C for one month, during which no phase separation was
      observed. The antimicrobial activity of the microemulsions was tested using the
      compendial method, observation of the kinetics of killing, and transmission
      electron microscopy (TEM) of microemulsion-exposed cultures of Pseudomonas
      aeruginosa PA01. These latter experiments on Ps. aeruginosa indicated distinct
      signs of membrane disruption. The results indicated that the microemulsions are
      self-preserved, and that their killing of microbial cultures is very rapid and
      may be the result of membrane activity.

PMID- 10945777
TI  - Factors influencing the ability of Pseudomonas putida strains epI and II to
      degrade the organophosphate ethoprophos.
AB  - Two strains of Pseudomonas putida (epI and epII), isolated previously from
      ethoprophos-treated soil, were able to degrade ethoprophos (10 mg 1(-1)) in a
      mineral salts medium plus nitrogen (MSMN) in less than 50 h with a concurrent
      population growth. Addition of glucose or succinate to MSMN did not influence the
      degrading ability of Ps. putida epI, but increased the lag phase before rapid
      degradation commenced with Ps. putida epII. The degrading ability of the two
      isolates was lost when the pesticide provided the sole source of phosphorus.
      Degradation of ethoprophos was most rapid when bacterial cultures were incubated
      at 25 and 37 degrees C. Pseudomonas putida epI was capable of completely
      degrading ethoprophos at a slow rate at 5 degrees C, compared with Ps. putida
      epII which could not completely degrade ethoprophos at the same time. Pseudomonas
      putida epI was capable of degrading ethoprophos when only 60 cells ml(-1) were
      used as initial inoculum. In contrast, Ps. putida epII was able to totally
      degrade ethoprophos when inoculum densities of 600 cells ml(-1) or higher were
      used. In general, longer lag phases accompanied the lower inoculum levels. Both
      isolates rapidly degraded ethoprophos in MSMN at pHs ranging from 5.5 to 7.6, but
      not at pH 5 or below.

PMID- 10945778
TI  - A comparison of methods for the detection of Escherichia coli O157:H7 from
      artificially-contaminated dairy products using PCR.
AB  - Rapid nucleic acid-based methods to detect human pathogens in foods are dependent
      on the reliability of the DNA or RNA extraction method used. Skim milk, non-fat
      dry milk, Cheddar and Brie cheese, and reconstituted whey powder were seeded with
      serially diluted (10(0)-10(7) cfu 10 ml(-1)) Escherichia coli O157:H7 and
      subjected to DNA extraction (i) directly from the food product using a solvent
      based procedure and (ii) using a guanidinium isothiocyanate (GITC) procedure
      after previous bacterial concentration. Both the efficiency of DNA extraction and
      the overall PCR detection limits were evaluated. In almost all instances, the
      total DNA yield using the solvent method was greater than that obtained for the
      concentration method. However, the purity of the DNA obtained after bacterial
      concentration was significantly better than that obtained after organic
      extraction alone. PCR detection limits after each DNA recovery method varied with
      the specific food, ranging from 10(1) to 10(4) cfu ml(-1) for all products except
      whey powder. DNA yields and subsequent PCR detection limits for reconstituted
      whey powder were extremely poor, and neither procedural changes nor the addition
      of PCR enhancement agents were able to improve recovery and/or detection. It is
      concluded that the efficiency of DNA extraction is an extremely important and
      frequently overlooked variable impacting the overall detection limits of PCR
      based detection strategies.

PMID- 10945779
TI  - Efficient method for the detection of microbially-produced antibacterial
      substances from food systems.
AB  - A novel method for the isolation of microbially-derived inhibitory substances
      from food sources was developed. The method involves an enrichment step coupled
      to a killing assay which is initially carried out in multiwell plates. The
      technique has advantages in that large numbers of samples can be tested in
      parallel. The assay can be completed in less than 60 h and is more sensitive than
      direct plating due to the enrichment step. This novel screening approach was
      compared with the standard direct plating approach in an effort to identify the
      antimicrobial potential of a number of Kefir grains. Kefir grains were incubated
      in 10% reconstituted skim milk for 20 h at 32 degrees C to enable production of
      any potential biopreservatives. Following overnight incubation, fermentates were
      aliquoted into multi-well plates and a known number of indicator cells was added
      to each well. The fermentates were incubated for a further 20 h and counts were
      carried out to determine whether a reduction in indicator cell numbers had
      occurred. A reduction in cell-forming units indicated the presence of an
      inhibitory substance and these inhibitory fermentates were selected for further
      investigation. Using the protocol outlined, Kefir fermentates capable of
      inhibiting Listeria innocua DPC1770 and Escherichia coli O157:H45 were
      identified.

PMID- 10945780
TI  - Expression of the hilA Salmonella typhimurium gene in a poultry Salm. enteritidis
      isolate in response to lactate and nutrients.
AB  - Pathogens express virulence genes in response to the combination of environmental
      conditions present in the host environment. The crop is the first
      gastrointestinal environment encountered in birds. However, feed withdrawal
      alters the crop environment resulting in an increased pH, and decreased
      concentrations of lactate, glucose and amino acids compared with unmoulted birds.
      Salmonella enteritidis infections increase significantly in hens that have been
      force moulted by feed withdrawal. The present study examined the effects of pH,
      carbohydrate sources, amino acids and lactate on expression of Salm. enteritidis
      virulence by measuring expression of hilA. The hilA gene encodes a
      transcriptional activator that regulates expression of Salmonella virulence genes
      in response to environmental stimuli. HilA expression was determined using a
      poultry isolate of Salm. enteritidis carrying a hilA-lacZY transcriptional fusion
      from Salm. typhimurium. The media used were Luria Bertani (LB) broth and LB broth
      diluted 1:5 (DLB). The expression of hilA was 2.9-fold higher in DLB broth
      compared with LB broth which suggested that there is a nutritional component to
      the regulation of hilA. Addition of 0.2% glucose, fructose or mannose to LB and
      DLB reduced hilA expression 1.5 to twofold. Addition of 0.2% Casaminoacids,
      arabinose, fucose, or lactose had little effect on hilA expression. Lactate (25
      and 50 mmmol 1-1) reduced hilA expression at pH 6, 5 and 4, with the lowest
      expression occurring at pH 4. Based on these results it appears that the
      composition of the crop lumen could potentially influence Salm. enteritidis
      virulence expression.

PMID- 10945781
TI  - Prevalence and virulence properties of Vibrio cholerae non-O1, Aeromonas spp. and
      Plesiomonas shigelloides isolated from Cambe Stream (State of Parana, Brazil).
AB  - The incidence of Vibrio cholerae, Aeromonas spp. and Plesiomonas shigelloides was
      determined in water samples from Cambe Stream. The samples were collected from
      seven different sites. The serogroups, virulence markers and drug resistance
      profiles were also evaluated. Twelve Aer. hydrophila, 12Aer. caviae, eight Aer.
      sobria, seven Ple. shigelloides and two V. cholerae non-O1 were isolated. They
      belonged to different serogroups and all produced haemolysis in different assays.
      Five of the Aeromonas strains and one of V cholerae non-O1 were positive for
      enterotoxin activity. Haemagglutination and its inhibition, using erythrocytes of
      different origins, was variable for Aeromonas spp. and V. cholerae, while none of
      the Ple. shigelloides haemagglutinated in association with any type of
      erythrocyte. All isolates exhibited multiple drug resistance. These results
      indicate that the occurrence of V. cholerae non-O1, Aeromonas spp. and Ple.
      shigelloides, in water used for vegetable irrigation, human recreation and animal
      consumption, among others, represents a potential risk for humans.

PMID- 10945782
TI  - Chitinases from Vibrio: activity screening and purification of chiA from Vibrio
      carchariae.
AB  - Fourteen species of Vibrio were screened for chitin-induced chitinase activity in
      culture medium. V. carchariae, V. alginolyticus 283 and V. campbellii showed high
      levels of activity. Screening on agar plates containing swollen chitin showed
      high levels of chitinase activity by the same three species, and also by V.
      fischeri and V. alginolyticus 284. An affinity purification procedure was
      developed for the chitinase from V. carchariae. The purified chitinase was active
      as a monomer with M(r) 63,000-66,000, and displayed activity toward polymeric
      chitin from acetylated chitosan or from crab shells. N-terminal sequence analysis
      and immunological cross-reactivity confirmed that the enzyme belongs to the group
      A/chiA family of bacterial chitinases.

PMID- 10945783
TI  - Production of catalase and glucose oxidase by Aspergillus niger using
      unconventional oxygenation of culture.
AB  - A novel method for increasing dissolved oxygen concentration in culture media has
      been developed. It involves adding hydrogen peroxide (H2O2) to the medium which
      is then decomposed to oxygen and water by catalase. Some factors affecting
      oxygenation of culture were investigated. Maximal oxygen concentration occurred
      in 50 ml of the medium containing 0-2 g wet mycelium and 0.2% glucose at pH 5.0.
      A new apparatus for automated addition of H2O2 to the bioreactor to keep the
      dissolved oxygen concentration constant over the range 1-100% +/- 2% was tested.
      A significant increase (over sixfold) of intracellular catalase activity was
      obtained while the dissolved oxygen concentration remained stable (30% +/- 2%).

PMID- 10945784
TI  - Changes in viability and macromolecular content of long-term batch cultures of
      Salmonella typhimurium measured by flow cytometry.
AB  - Exposure of many Gram-negative bacteria to prolonged starvation induces
      alternative programmes of gene expression, along with a transition into a dormant
      condition sometimes referred to as a viable non-culturable (VBNC) state.
      Knowledge of how pathogenic species respond to nutrient limitation is therefore
      important for their detection and dissemination. This study used flow cytometry,
      coupled with fluorescent dyes for viability and macromolecular content, to study
      the responses of the pathogen Salmonella typhimurium to prolonged batch culture.
      Statistical analysis of the flow cytometric data, together with total and
      culturable cell counts, failed to demonstrate a VBNC state in this pathogen,
      contrary to reports from other workers. Analysis of rRNA and protein content
      identified a small proportion of cells in 110 day-old cultures that represented
      an active sub-population. This observation may provide an explanation for the
      long-term survival properties of this organism during prolonged exposure to
      nutrient limitation, as well as the high degree of heterogeneity observed in
      labelled cells.

PMID- 10945785
TI  - Alterations in extracellular substances during the biofilm development of
      Pseudomonas aeruginosa on aluminum plates.
AB  - The chemical moieties during biofilm formation of Pseudomonas aeruginosa on
      aluminium plates were examined for a period of 17 days. The effect of fluid
      shearing upon biofilm formation has also been investigated. The Fourier transform
      infrared (FTIR) spectrum of the biofilm taken on the fifth day showed significant
      differences compared with the spectrum of the unattached bacterial cells,
      indicating that structural changes or modifications of the cell envelope had
      taken place during the development of the biofilm. Major changes were also
      observed in the spectrum during the subsequent development of the biofilm from
      day 5 to day 17. The increasing intensity of a band corresponding to the
      symmetric stretching mode of the carboxyl group indicated interactions between
      the carboxyl group and the aluminium surface. Increased bacterial colonization
      was also observed at the air-water interface of the aluminium plates when
      compared with the middle and the bottom parts. Changes in FTIR spectra of the
      biofilm at the bottom, at the middle, and at the air-water interface suggest that
      the mechanisms of bacterial attachment differed by a -COO(-) interaction at the
      air-water interface, and by both -COO(-) and NH3(+) groups beneath the water
      surface.

PMID- 10945786
TI  - Incorporation of eicosapentaenoic and docosahexaenoic acids by a yeast (FO726A).
AB  - An eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-incorporating
      yeast, FO726A, was putatively identified as Candida guilliermondii on the basis
      of morphological, physiological and biochemical characteristics. Culture
      conditions for FO726A were investigated with respect to cell mass productivity,
      cellular accumulation of total lipid, triglyceride (TG), EPA and DHA. When grown
      at 20 degrees C for 24 h in an optimal medium containing 1 g scrap fish oil, the
      yeast yielded 820 mg dry cells which consisted of 40.7% lipid, 40.2% protein and
      14.1% carbohydrate. The lipid (334mg) consisted of 300 mg TG (36.6% of dry
      cells), 23.2 mg EPA (2.8%) and 54.8 mg DHA (6.7%), and the recovery rates of EPA
      and DHA from the fish oil were 27.1 and 43.6%, respectively. The positional
      distributions of fatty acids in the TG from the yeast were then investigated and
      compared with those in the TG from the fish oil. The EPA and DHA in the fish oil
      were concentrated more in the sn-1,3 positions (8.8 and 13.7%, respectively) than
      in the sn-2 position (3.7 and 10.8%, respectively). In the case of the TG from
      the yeast, EPA was present to a greater extent in the sn-1,3 positions than in
      the sn-2 position. In contrast, DHA was preferentially present in the sn-2
      position, approximately twice that in the sn-1,3 positions.

PMID- 10945787
TI  - Influence of different substrate limitations on the yield, composition and
      molecular mass of exopolysaccharides produced by Lactococcus lactis subsp.
      cremoris in continuous cultures.
AB  - The type of substrate limitation had a remarkable influence on the molecular mass
      of exopolysaccharides (EPS) produced by Lactococcus lactis subsp. cremoris NIZO
      B40 and NIZO B891. Under glucose/energy limitation, the molecular mass was much
      smaller than under leucine or phosphate limitation, resulting in a marked
      decrease of the intrinsic viscosity of this EPS. The sugar composition of EPS
      produced by both strains, and the phosphate content of EPS produced by NIZO B40,
      were not affected by the type of nutrient limitation. Both strains produced
      comparable amounts of EPS under leucine and glucose limitation, but the
      efficiency of EPS production was highest under glucose limitation. The EPS yields
      of the phosphorylated B40 EPS as well as the unphosphorylated B891 EPS were
      reduced, with about 40% under conditions of phosphate limitation.

PMID- 10945788
TI  - Denitrification by indigenous microbial populations of river water measured using
      membrane inlet mass spectrometry.
AB  - The major process that reduces nitrate levels in soils and water is
      denitrification, which converts nitrate and nitrite into gaseous forms of
      nitrogen, which are then released into the atmosphere. This study used membrane
      inlet mass spectrometry (MIMS) to investigate denitrification in river water
      bacterial isolates supplied with nitrate and succinate as an energy source as
      well as in the total population by provision of different carbon compounds to
      untreated river water samples. Substantial variation was observed in the gases
      detected with nitrogen, nitrous oxide and nitric oxide all being produced by one
      or more of the isolates. The indigenous river population as a whole was found to
      respond very differently to the addition of different carbon sources. Peak
      nitrogen levels differed by nearly 1 mmol 1(-1) and nitrous oxide by
      approximately 0.5 mmol 1(-1) depending on which carbon source was supplied.
      Nitric oxide was only detected when glycerol was supplied as the carbon source.
      These results demonstrate the complex interactions involved in nitrogen cycling
      and suggest that with careful management it may be possible to stimulate
      particular consortia of micro-organisms to reduce more nitrate to harmless
      nitrogen rather than nitrous oxide, a known greenhouse gas.

PMID- 10945789
TI  - 16S to 23S rRNA spacer fragment length polymorphism of Salmonella enterica at
      subspecies and serotype levels.
AB  - The variation in the lengths of the internal transcribed spacer (ITS) between 16S
      and 23S rRNA genes of 101 strains representing 58 serotypes of Salmonella
      enterica (used for Salm. choleraesuis) subsp. enterica (I), salamae (II),
      arizonae (IIIa), diarizonae (IIIb), houtenae (IV) and indica (VI) was used for
      typing by PCR amplification. Ten fragment lengths were observed by denaturing
      polyacrylamide gel electrophoresis on an automatic DNA sequencer resulting in 21
      unique fragment patterns. Ten out of the 58 serotypes showed specific patterns
      but 48 serotypes were not fully differentiated. More than one ITS pattern was
      observed in seven serotypes. Five of the 21 fragment patterns contained
      representatives of more than one subspecies. Under non-denaturing electrophoresis
      conditions, serotype specificity was obtained but precise ITS fragment length
      determination was not possible. DNA sequence comparison between ITSs of
      individual rrn operons is needed to further interpret ITS diversity within Salm.
      enterica at serotype and subspecies levels.

PMID- 10945790
TI  - Survival of Salmonella in bathrooms and toilets in domestic homes following
      salmonellosis.
AB  - The survival and environmental spread of Salmonella bacteria from domestic
      toilets was examined in homes, where a family member had recently suffered an
      attack of salmonellosis. In four out of six households tested, Salmonella
      bacteria persisted in the biofilm material found under the recess of the toilet
      bowl rim which was difficult to remove with household toilet cleaners. In two
      homes Salmonella bacteria became incorporated into the scaly biofilm adhering to
      the toilet bowl surface below the water line. Salmonella enteritidis persisted in
      one toilet for 4 weeks after the diarrhoea had stopped, despite the use of
      cleaning fluids. Salmonellas were not isolated from normally dry areas such as,
      the toilet seat, the flush handle and door handle. Toilet seeding experiments
      were set up with Salmonella enteritidis PT4 to mimic environmental conditions
      associated with acute diarrhoea. Flushing the toilet resulted in contamination of
      the toilet seat and the toilet seat lid. In one out of three seedings, Salmonella
      bacteria were also isolated from an air sample taken immediately after flushing,
      indicating that airborne spread of the organism could contaminate surfaces in the
      bathroom. In the seeded toilet Salmonella bacteria were isolated from the biofilm
      in the toilet bowl below the waterline for up to 50 d after seeding, and also on
      one occasion from the bowl water. The results suggest that during diarrhoeal
      illness, there is considerable risk of spread of Salmonella infection to other
      family members via the environment, including contaminated hands and surfaces in
      the toilet area.

PMID- 10945791
TI  - The response of Aeromonas hydrophila to oxidative stress induced by exposure to
      hydrogen peroxide.
AB  - Aeromonas hydrophila, an opportunist human pathogen of low virulence, was shown
      to display a high degree of sensitivity upon exposure to hydrogen peroxide. As
      with other species, Aer. hydrophila is able to develop the capacity to resist
      loss of viability induced by such oxidative stress. Development of stress
      resistance follows the archetypal profile where pre-exposure of a population to
      sub-lethal levels of H2O2 stimulates onset of tolerance to further exposure.
      Acquisition of tolerance critically requires nascent protein synthesis. Further
      analysis demonstrated population growth phase influences the degree of
      sensitivity of the organism. Late stationary phase cultures demonstrate a
      decreased sensitivity compared with younger populations. Significantly, it was
      also determined that stock culture age influenced the level of sensitivity of the
      derived experimental culture, where an increased stock culture age corresponded
      with enhanced resistance to H2O2. These data show that Aer. hydrophila population
      phenotype is influenced by the phenotype of the donor stock culture.

PMID- 10945792
TI  - High expression of the penicillin G acylase gene (pac) from Bacillus megaterium
      UN1 in its own pac minus mutant.
AB  - By marker exchange mutagenesis, Bacillus megaterium strain UN-1 (Bm-UN1) was used
      to prepare a mutant strain B. megaterium UN-cat (Bm-UNcat) lacking the penicillin
      G acylase gene (pac). The pac gene from Bm-UN1 was subcloned into pTF6 and the
      resultant plasmid, pBA402, was introduced into Bm-UNcat and Bacillus subtilis. Bm
      UNcat harbouring pBA402 produced high penicillin G acylase (PAC) activity of
      13.7, 19.5 and 20.4 U ml(-1) at 24, 36 and 48 h of culture, respectively. This
      was two- to fivefold higher than PAC produced by B. subtilis harbouring pBA402
      and about 20-fold higher than PAC produced by the parent strain, Bm-UN1.

PMID- 10945793
TI  - Role of rhamnolipid biosurfactants in the uptake and mineralization of hexadecane
      in Pseudomonas aeruginosa.
AB  - A study was undertaken to investigate the mechanisms for biosurfactant-enhanced
      hexadecane uptake into Pseudomonas aeruginosa. Two strains of Ps. aeruginosa were
      studied, one producing rhamnolipids (PG201) and the other rhamnolipid deficient
      (UO299). Rhamnolipids produced by PG201 acted to increase the solubility of n
      hexadecane in the culture medium (from 1.84 to 22.76 microg l(-1). Rates of(l4)C
      n-hexadecane uptake and mineralization were higher in PG201 than in UO299.
      However, the degree of difference was lower than expected. Additional studies
      were carried out on the cell surface properties of the two strains. During growth
      on n-hexadecane, the cell surface hydrophobicity of both PG201 (50.5%) and UO299
      (33.7%) increased compared with that observed in water-soluble growth substrates
      (7-8%). Studies were also carried out to ascertain any energy requirements for
      the transport of n-hexadecane into Ps. aeruginosa cells. The addition of CCCP (an
      inhibitor of cytochrome oxidase which thereby blocks oxidative phosphorylation)
      at a range of concentrations caused a marked decrease in n-hexadecane uptake,
      indicating that n-hexadecane uptake in Ps. aeruginosa is an energy-dependent
      process. These studies support the hypothesis of alkane transport into microbial
      cells by direct contact with larger alkane droplets and by pseudosolubilization.
      Also, it appears that both mechanisms occur simultaneously.

PMID- 10945794
TI  - Comparison of methods for isolating Salmonella bacteria from faeces of naturally
      infected pigs.
AB  - A series of experiments was conducted using faecal samples collected from
      commercial swine farms to evaluate the effects of variation in methods used for
      the detection of Salmonella bacteria. The primary objective of the studies was to
      compare the protocols routinely used in two laboratories in the USA. The studies
      included five experiments comparing the enrichment protocols used routinely in
      the respective laboratories (Method 1: 10 g faeces--buffered peptone water (BPW)
      pre-enrichment--selective enrichment in Rappaport/Vassiliadis (RV) broth; Method
      2: approximately 1g faeces--primary enrichments in tetrathionate and Hajna GN
      broths--secondary enrichment in RV broth). The effects of enrichment temperatures
      (37 vs 42 degrees C) using RV broth (two experiments) and delayed secondary
      enrichment (four experiments) were also evaluated. Direct comparison of Method 1
      and Method 2 indicated comparable results. However, when compared using faecal
      samples of equal weight, the Method 2 enrichment protocol was more sensitive for
      detecting Salmonella bacteria than the Method 1 protocol. Enrichment in RV at 42
      degrees C was superior to 37 degrees C, particularly for samples that were pre
      enriched in BPW. Delayed secondary enrichment increased detection of Salmonella
      bacteria in swine faeces. These results highlight the imperfect sensitivity of
      culture methods, and the need for researchers to consider the sensitivity of
      bacteriological methods in the design and interpretation of the results of
      epidemiologic studies based on faecal culture.

PMID- 10945795
TI  - Determination of metabolic activity of streptomycetes in soil microcosms.
AB  - Two Streptomyces griseus strains were isolated from different soil types. S.
      griseus CAG17 strain was isolated from an agricultural area with low organic
      matter but rich in phosphorus content and S. griseus 26K strain was isolated from
      a forest area rich in organic matter with a low phosphorus content. The survival
      and metabolic activity of these isolates were studied in dynamic sterile soil
      microcosm systems. The fitness of each isolate was studied by re-inoculation in a
      soil type different from its origin. Maximum percentage of germination and
      respiration rates occurred within the first 48 h after each soil turnover
      (removal and addition of certain soil volumes). Data suggested that S. griseus
      CAG17 survived better independently of the soil type in comparison with S.
      griseus 26K which sporulated within the first 12 h after inoculation. Incubation
      temperatures did affect the lifecycles in relation to soil type. For example, the
      lowest temperature tested, 22 degrees C, was more favourable for extended
      germination and adaptation in general but revealed lesser spore numbers in the
      'foreign' soil environment. Monitoring metabolic activity by estimation of
      urease, phosphatases and dehydrogenase-specific activities, between 18 and 35
      degrees C incubation temperatures, was a reliable method for studying the
      survival and growth of streptomycete populations in soil. Results also confirmed
      that respiration rate and enzyme-specific activity corresponded with spore counts
      in long-term experiments which were designed for the investigation of survival
      and growth of S. griseus CAG17. Under selective pressure by heavy metals, in soil
      microcosm systems, metabolic activity proved a useful tool for the investigation
      of streptomycete activity. These methods could also be applied in agricultural
      field studies for monitoring microbial populations under conditions where various
      'pollutants' are present in soil samples.

PMID- 10945796
TI  - Production of rhodanese by bacteria present in bio-oxidation plants used to
      recover gold from arsenopyrite concentrates.
AB  - Considerably larger quantities of cyanide are required to solubilize gold
      following the bio-oxidation of gold-bearing ores compared with oxidation by
      physical-chemical processes. A possible cause of this excessive cyanide
      consumption is the presence of the enzyme rhodanese. Rhodanese activities were
      determined for the bacteria most commonly encountered in bio-oxidation tanks.
      Activities of between 6.4 and 8.2 micromol SCN min(-1) mg protein(-1) were
      obtained for crude enzyme extracts of Thiobacillus ferrooxidans, Thiobacillus
      thiooxidans and Thiobacillus caldus, but no rhodanese activity was detected in
      Leptospirillum ferrooxidans. Rhodanese activities 2-2.5-fold higher were found in
      the total mixed cell mass from a bio-oxidation plant. T. ferrooxidans synthesized
      rhodanese irrespective of whether it was grown on iron or sulphur. With a PCR
      based detection technique, only L. ferrooxidans and T. caldus cells were detected
      in the bio-oxidation tanks. As no rhodanese activity was associated with L.
      ferrooxidans, it was concluded that T. caldus was responsible for all of the
      rhodanese activity. Production of rhodanese by T. caldus in batch culture was
      growth phase-dependent and highest during early stationary phase. Although the
      sulphur-oxidizing bacteria were clearly able to convert cyanide to thiocyanate,
      it is unlikely that this rhodanese activity is responsible for the excessive
      cyanide wastage at the high pH values associated with the gold solubilization
      process.

PMID- 10945797
TI  - Dissociative psychopathology, non-epileptic seizures, and neurology.

PMID- 10945798
TI  - Chronic fatigue syndrome: is it physical?

PMID- 10945799
TI  - What contributes to quality of life in patients with Parkinson's disease?

PMID- 10945800
TI  - Can a neuropsychological follow up contribute to the diagnosis of parkinsonian
      syndromes?

PMID- 10945801
TI  - Tetanus.

PMID- 10945802
TI  - Antonio Grossich (1849-1926).

PMID- 10945803
TI  - Strength and physiological response to exercise in patients with chronic fatigue
      syndrome.
AB  - OBJECTIVE: To measure strength, aerobic exercise capacity and efficiency, and
      functional incapacity in patients with chronic fatigue syndrome (CFS) who do not
      have a current psychiatric disorder. METHODS: Sixty six patients with CFS without
      a current psychiatric disorder, 30 healthy but sedentary controls, and 15
      patients with a current major depressive disorder were recruited into the study.
      Exercise capacity and efficiency were assessed by monitoring peak and submaximal
      oxygen uptake, heart rate, blood lactate, duration of exercise, and perceived
      exertion during a treadmill walking test. Strength was measured using twitch
      interpolated voluntary isometric quadriceps contractions. Symptomatic measures
      included physical and mental fatigue, mood, sleep, somatic amplification, and
      functional incapacity. RESULTS: Compared with sedentary controls, patients with
      CFS were physically weaker, had a significantly reduced exercise capacity, and
      perceived greater effort during exercise, but were equally unfit. Compared with
      depressed controls, patients with CFS had significantly higher submaximal oxygen
      uptakes during exercise, were weaker, and perceived greater physical fatigue and
      incapacity. Multiple regression models suggested that exercise incapacity in CFS
      was related to quadriceps muscle weakness, increased cardiovascular response to
      exercise, and body mass index. The best model of the increased exercise capacity
      found after graded exercise therapy consisted of a reduction in submaximal heart
      rate response to exercise. CONCLUSIONS: Patients with CFS were weaker than
      sedentary and depressed controls and as unfit as sedentary controls. Low exercise
      capacity in patients with CFS was related to quadriceps muscle weakness, low
      physical fitness, and a high body mass ratio. Improved physical fitness after
      treatment was associated with increased exercise capacity. These data imply that
      physical deconditioning helps to maintain physical disability in CFS and that a
      treatment designed to reverse deconditioning helps to improve physical function.

PMID- 10945804
TI  - What contributes to quality of life in patients with Parkinson's disease?
AB  - OBJECTIVE: To identify the factors that determine quality of life (QoL) in
      patients with idiopathic Parkinson's disease in a population based sample.
      Quality of life (QoL) is increasingly recognised as a critical measure in health
      care as it incorporates the patients' own perspective of their health. METHODS:
      All patients with Parkinson's disease seen in a population based study on the
      prevalence of parkinsonism were asked to complete a disease-specific QoL
      questionnaire (PDQ-39) and the Beck depression inventory. A structured
      questionnaire interview and a complete neurological examination, including the
      Hoehn and Yahr scale, the Schwab and England disability scale, the motor part of
      the unified Parkinson's disease rating scale (UPDRS part III), and the mini
      mental state examination were performed by a neurologist on the same day.
      RESULTS: The response rate was 78%. The factor most closely associated with QoL
      was the presence of depression, but disability, as measured by the Schwab and
      England scale, postural instability, and cognitive impairment additionally
      contributed to poor QoL. Although the UPDRS part III correlated significantly
      with QoL scores, it did not contribute substantially to predicting their variance
      once depression, disability, and postural instability had been taken into
      account. In addition, patients with akinetic rigid Parkinson's disease had worse
      QoL scores than those with tremor dominant disease, mainly due to impairment of
      axial features. CONCLUSION: Depression, disability, postural instability, and
      cognitive impairment have the greatest influence on QoL in Parkinson's disease.
      The improvement of these features should therefore become an important target in
      the treatment of the disease.

PMID- 10945806
TI  - Repetitive speech phenomena in Parkinson's disease.
AB  - OBJECTIVES: Repetitive speech phenomena are morphologically heterogeneous
      iterations of speech which have been described in several neurological disorders
      such as vascular dementia, progressive supranuclear palsy, Wilson's disease, and
      Parkinson's disease, and which are presently only poorly understood. The present,
      prospective study investigated repetitive speech phenomena in Parkinson's disease
      to describe their morphology, assess their prevalence, and to establish their
      relation with neuropsychological and clinical background data. METHODS: Twenty
      four patients with advanced Parkinson's disease and 29 subjects with mid-stage,
      stable idiopathic disease were screened for appearance, forms, and frequency of
      repetitive speech phenomena, and underwent a neuropsychological screening
      procedure comprising tests of general mental functioning, divergent thinking and
      memory. Patients with advanced Parkinson's disease had a significantly higher
      disease impairment, longer disease duration, and an unstable motor response to
      levodopa with frequent on-off fluctuations. Both groups were well matched as to
      their demographical, clinical, and cognitive background. Perceptual speech
      evaluation was used to count and differentiate forms of repetitive speech
      phenomena in different speech tasks. To compare the effect of the motor state,
      the appearance of repetitive speech phenomena was also assessed in a subgroup of
      patients with advanced Parkinson's disease during the on versus the off state.
      RESULTS: Speech repetitions emerged mainly in two variants, one hyperfluent,
      formally resembling palilalia, and one dysfluent, stuttering-like. Both forms
      were present in each patient producing repetitive speech phenomena. The
      repetitive speech phenomena appeared in 15 patients (28.3 %), 13 of whom belonged
      to the advanced disease group, indicating a significant preponderance of
      repetitive speech phenomena in patients with a long term, fluctuating disease
      course. Repetitive speech phenomena appeared with almost equal frequency during
      the on and the off state of patients with advanced Parkinson's disease. Their
      distribution among different variants of speech was disproportional, with effort
      demanding speech tasks producing a significantly higher number of repetitive
      speech phenomena over semiautomatic forms of speech. CONCLUSIONS: In idiopathic
      Parkinson's disease repetitive speech phenomena seem to emerge predominantly in a
      subgroup of patients with advanced disease impairment; manifest dementia is not a
      necessary prerequisite. They seem to represent a deficit of motor speech control;
      however, linguistic factors may also contribute to their generation. It is
      suggested that repetitions of speech in Parkinson's disease represent a
      distinctive speech disorder, which is caused by changes related to the
      progression of Parkinson's disease.

PMID- 10945805
TI  - Neuropsychological follow up in patients with Parkinson's disease, striatonigral
      degeneration-type multisystem atrophy, and progressive supranuclear palsy.
AB  - OBJECTIVES: Impairment of executive function is frequent in Parkinson's disease
      (PD), striatonigral degeneration-type multisystem atrophy (SND), and progressive
      supranuclear palsy (PSP); sometimes frank dementia is also present. However, the
      progression of cognitive decline has not been adequately studied. The objectives
      were to delineate the progression of cognitive impairment in these parkinsonisms
      and to elucidate interdisease differences. METHODS: Twenty three patients with
      SND and 21 with PSP, referred consecutively, and 18 patients with PD matched for
      severity of parkinsonism were compared on a comprehensive battery of cognitive
      tests and motor invalidity scales. A mean of 21 months later (range 18-24 months)
      the patients were called for retesting. RESULTS: Only 12 patients with PD
      (66.6%), 14 with SND (60.8%), and 11 with PSP (52.4%) were retested; those who
      dropped out refused, had died, or were too disabled. The patients with PSP
      performed worse than patients with PD or SND in the short tale, verbal fluency,
      visual search, and Benton tests at first evaluation. Overall cognitive
      performance was similar in the PD and SND groups except that the SND group did
      significantly worse on the verbal fluency test. Between group comparison of
      changes in scores from first to second evaluation showed that patients with PSP
      deteriorated significantly in the Nelson test compared with patients with PD or
      SND, and that patients with PSP or SND declined significantly on the visual
      search test compared with patients with PD. There was no difference between the
      groups for motor decline. Two patients with PSP were demented (DSM IV criteria)
      at first evaluation and six at second evaluation; no patients with PD or SND were
      demented at either evaluation. CONCLUSIONS: The greater decline of patients with
      PSP in attention, set shifting, and categorisation abilities is probably related
      to the conspicuous frontal deafferentation associated with direct premotor and
      prefrontal involvement, and to dysfunction of the midbrain ascending activating
      system, known to occur in PSP.

PMID- 10945807
TI  - Neuropsychological outcome after unilateral pallidotomy for the treatment of
      Parkinson's disease.
AB  - OBJECTIVE: To assess the long term cognitive outcome of unilateral posteroventral
      pallidotomy (PVP) and the overall efficacy of the surgery. METHODS: Forty two (29
      left and 13 right PVP) patients with Parkinson's disease underwent neurological
      and neuropsychological testing before PVP and at 3 and 12 months after PVP. The
      neuropsychological testing battery emphasised measures of verbal learning and
      memory, visuospatial abilities, speed of information processing, executive
      functioning, and affective functioning. RESULTS: All patients demonstrated motor
      improvements after surgery during their off state, and 86% of patients also
      showed improvements in motor functioning in their on state. Repeated measures
      ANOVA showed significant improvements in confrontational naming, visuospatial
      organisation, and affective functioning 3 months and 12 months after surgery,
      with inconsistent improvements in executive functioning 12 months post-PVP.
      Patients demonstrated a transient impairment in verbal memory, with verbal
      learning performance returning to baseline 12 months post-PVP after a significant
      decline 3 months after PVP. When three patients with lesions extending outside of
      the PVP were excluded from the analysis, a decline in verbal fluency performance
      after PVP was not found to be significant. Differences due to side of lesion
      placement were not found on any of the cognitive measures. CONCLUSIONS: In the
      largest long term follow up study reported to date, the cognitive changes found
      up to a year after PVP are minimal compared with the robust improvements in motor
      function. The findings highlight the need to investigate the relation between the
      specific fibre tracts affected by the lesions and cognitive outcome.

PMID- 10945808
TI  - Long term outcome of unilateral pallidotomy: follow up of 15 patients for 3
      years.
AB  - OBJECTIVES: With the advent of new antiparkinsonian drug therapy and promising
      results from subthalamic and pallidal stimulation, this study evaluated the long
      term efficacy of unilateral pallidotomy, a technique which has gained popularity
      over the past decade for the management of advanced Parkinson's disease. METHODS:
      The 15 patients reported here are part of the original cohort of 24 patients who
      underwent posteroventral pallidotomy for motor fluctuations and disabling
      dyskinesias 3 years ago as part of a prospective study. Evaluation scales
      included the unified Parkinson's disease rating scale, the Goetz dyskinesia
      scale, and the Purdue pegboard test. RESULTS: When compared with the
      prepallidotomy scores, the reduction in the limb dyskinesias and off state tremor
      scores persisted on the side contralateral to pallidotomy at the end of 3 years
      (dyskinesias were reduced by 64% (p<0.01) and tremor by 63% (p<0.05). Other
      measures tended to deteriorate. The dosage of antiparkinsonian medications did
      not change significantly from 3 months prepallidotomy to 3 years postpallidotomy.
      CONCLUSIONS: Although unilateral pallidotomy is useful in controlling the
      contralateral dyskinesias and tremor 3 years after surgery, all other early
      benefits disappear and activities of daily living continue to worsen.

PMID- 10945809
TI  - Predictive control of muscle responses to arm perturbations in cerebellar
      patients.
AB  - OBJECTIVES: To examine changes in predictive control of early antagonist
      responses to limb perturbations in patients with defined lesions of the
      cerebellum. METHODS: Eight cerebellar patients and eight sex and age matched
      control subjects participated. Subjects held a handle that was rotated around the
      elbow joint. They were instructed to hold the forearm at 90 degrees flexion
      against a mechanical perturbation. Extensor torque (5 Nm) was applied for 140 ms
      (pulse), or for 1400 ms (step) through an external motor. Motor responses were
      tested under two different conditions of anticipatory information. In the
      expected condition, subjects anticipated and received a pulse. Under the
      unexpected condition, subjects expected steps, but received unexpected pulses.
      Biceps and triceps EMG as well as angular kinematics were compared between
      expected and unexpected pulse perturbations to quantify possible effects of
      prediction. RESULTS: In all healthy subjects, the degree of overshoot in the
      return flexion movement was significantly less in expected pulse perturbations
      compared with unexpected trials. The degree of amplitude reduction was
      significantly smaller in the patient group than in the control group (22.8% v
      40.0%). During the expected trials, latency of peak triceps activity was on
      average 20% shorter in the control group, but 4% larger in the cerebellar
      patients. CONCLUSIONS: In the expected condition, controls achieved a significant
      reduction in angular amplitude by generating triceps activity earlier, whereas
      the ability to use prediction for adjusting early antagonist responses after limb
      perturbation was impaired in cerebellar patients.

PMID- 10945810
TI  - Relation between abnormal patterns of muscle activation and response to common
      peroneal nerve stimulation in hemiplegia.
AB  - OBJECTIVE: To investigate the relation between response to common peroneal nerve
      stimulation, timed to the swing phase of walking, and abnormal ankle movement and
      muscle activation patterns. METHOD: Eighteen patients who took part had a drop
      foot and had had a stroke at least 6 months before the study Twelve age matched
      normal subjects were also studied. Response to stimulation was measured by
      changes in the speed and effort of walking when the stimulator was used. Speed
      was measured over 10 m and effort by the physiological cost index. Abnormal ankle
      movement and muscle activation were measured in a rig by ability to follow a
      tracking signal moving sinusoidally at either 1 or 2 Hz, resistance to passive
      movement, and EMG activity during both passive and active movements. Indices were
      derived to define EMG response to passive stretch, coactivation, and ability to
      activate muscles appropriately during active movement RESULTS: Different
      mechanisms underlying the drop foot were seen. Results showed that patients who
      had poor control of ankle movement and spasticity, demonstrated by stretch reflex
      and coactivation, were more likely to respond well to stimulation. Those with
      mechanical resistance to passive movement and with normal muscle activation
      responded less well. CONCLUSIONS: The results support the hypothesis that
      stimulation of the common peroneal nerve to elicit a contraction of the anterior
      tibial muscles also inhibits the antagonist calf muscles. The technique used may
      be useful in directing physiotherapy by indicating the underlying cause of the
      drop foot.

PMID- 10945811
TI  - Enhanced B7 costimulatory molecule expression in inflammatory human sural nerve
      biopsies.
AB  - OBJECTIVES: To define the role of the costimulatory molecules B7-1 and B7-2 in
      inflammatory disorders of the peripheral nervous system. B7 molecules are
      essential for effective antigen presentation and may determine the
      differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune
      response and disease course. METHODS: Forty nine sural nerve biopsies from
      patients with neuroborreliosis, Guillain-Barre syndrome (GBS), chronic
      inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary
      neuropathies, and those with no detectable abnormality were investigated. The
      expression of B7-1 and B7-2 mRNA and protein was investigated by polymerase chain
      reaction (PCR) and immunocytochemistry. RESULTS: B7-1 mRNA was strongly
      upregulated in both cases of neuroborreliosis, in two cases of GBS and one case
      of variant CIDP. Moderate to low levels were detected in the remaining GBS and
      CIDP biopsies and were rarely found in a non-inflammatory control group
      consisting of hereditary neuropathy and normal nerves. At the immunocytochemical
      level, strong expression of B7-1 protein was found in both neuroborreliosis
      cases, and moderate or low expression in six of eight GBS cases and seven of 17
      CIDP cases investigated, whereas only one of five non-inflammatory control nerves
      showed staining, which was very weak. In neuroborreliosis, B7-1 protein was found
      very pronounced in epineurial infiltrates, whereas in GBS and CIDP, labelling was
      predominantly endoneurial and localised to putative macrophages. B7-2 mRNA and
      protein were expressed only at low levels in neuroborreliosis and selected
      autoimmune neuropathy cases, and were essentially absent from non-inflammatory
      controls. CONCLUSIONS: B7 molecules are expressed in the peripheral nervous
      system and regulated during disease, and their presence in macrophages underlines
      the putative function of endoneurial macrophages as local antigen presenting
      cells in the immunopathology of peripheral nerve. B7-1 rather than B7-2 is
      preferentially upregulated, possibly promoting the induction of a Th-1-type T
      cell response within the nerve.

PMID- 10945812
TI  - Low frequency of replication errors in primary nervous system tumours.
AB  - OBJECTIVES: Automated DNA technology was used to analyze the incidence of
      microsatellite instability (MIN) among the most frequent types of adult primary
      CNS tumours and to determine its relation with clinicopathological
      characteristics. METHODS: Fifty six gliomas, 32 meningiomas and 11 schwannomas
      were screened for size changes at eight microsatellite loci using fluorescent
      polymerase chain reaction (PCR) followed by fragment analysis in an automated
      sequencer. A tumour was considered as MIN+ when a different electrophoretic
      pattern between constitutional and tumour DNA was evidenced in one or more
      microsatellite markers and as replication error positive (RER+) when at least 25%
      of the markers analyzed (2/8) showed instability. The MIN phenotype was
      correlated with relevant clinical and pathological parameters. RESULTS: Globally,
      instability was found in 19/767 analyses (2.47%), with a higher rate among
      tetranuceotide than dinucleotide repeats (chi(2) test, p=0.018). Ten gliomas
      (17.9%), two meningiomas (6.3%), and two schwannomas (18.2%) were MIN+, whereas
      one glioma (1.8%), two meningiomas (6.3%), and one schwannoma (9.1%) were
      classified as RER+. A possible association between microsatellite instability and
      a shorter duration of clinical course was found in meningiomas. The MIN+
      phenotype was more frequent in spinal than intracranial schwannomas (Fisher's
      exact test, p=0.018). No other significant association with clinical or
      histological features was detected. CONCLUSIONS: Although microsatellite
      instability can be demonstrated at a low rate in some primary CNS tumours, a true
      replication error phenotype (revealed by widespread microsatellite instability at
      numerous loci) is uncommon and unlikely to play an important part in the
      pathogenesis of these neoplasms. This form of instability was more frequent in
      tetranucleotide than in dinucleotide repeats. To our knowledge, this is the first
      report of MIN in schwannomas, where it was associated with the spinal
      localisation of the tumour.

PMID- 10945813
TI  - Incidence and prevalence of neurological disorders associated with HIV since the
      introduction of highly active antiretroviral therapy (HAART).
AB  - OBJECTIVE: To determine the change of incidence and prevalence of neurological
      disorders caused by the human immunodeficiency virus (HIV) and opportunistic
      infections in HIV positive patients under treatment since the introduction of
      highly active antiretroviral therapy (HAART). METHODS: The data of all HIV
      infected patients were retrospectively analysed, who were examined in the HIV
      outpatients clinic of the neurological department of the University Clinic Essen
      between 1995 and 1998 (n=563, total number of visits=735). Data from identified
      patients were divided into two groups according to the time of examination from
      1995 to 1996 (334 visits) and from 1997 to 1998 (401 visits). The incidence and
      prevalence of neurological disorders were statistically compared between both
      time intervals. RESULTS: Significantly more patients received HAART in 1997-8
      (p<0. 001) and mean CD4+ cell count was significantly higher in 1997-8 (p<0.001).
      The prevalence of HIV associated dementia and HIV associated polyneuropathy were
      significantly lower in 1997-8 (both: p=0.02) and the incidence of toxoplasma
      encephalitis decreased from 5.7% in 1995-6 to 2.2% in 1997-8 (p=0.015). Based on
      the small number of patients significant changes in HIV associated myopathy,
      progressive multifocal leukoencephalopathy, cryptoccocal meningitis, and
      cytomegalovirus-encephalitis could not be detected. CONCLUSION: The prevalence of
      the most frequent HIV associated neurological disorders and incidence of
      toxoplasma encephalitis decreased since the introduction of HAART. This may be
      due to the improvement of immunostatus by HAART as demonstrated by the higher
      CD4+ cell count in the later time interval. Direct antiretroviral effects within
      the nervous system may be considered causative as well. The prevalence and
      incidence of HIV associated neurological disorders and opportunistic CNS
      infections decreased after introduction of HAART.

PMID- 10945814
TI  - Infection related to intracranial pressure monitors in adults: analysis of risk
      factors and antibiotic prophylaxis.
AB  - OBJECTIVE: Infection is a complication related to intracranial pressure
      monitoring devices. The timing, duration, and role of prophylactic antimicrobial
      agents against intracranial pressure monitor (ICPM) related infection have not
      previously been well defined. Risk factors and selection, duration, and timing of
      antibiotic prophylaxis in patients with ICPMs were evaluated. METHODS: Records of
      all consecutive patients who underwent ICPM insertion between 1993 and 1996 were
      reviewed. Patients included were older than 12 years with an ICPM placed for at
      least 24 hours. Exclusion criteria consisted of ICPM placed before admission or
      documented CSF infection before or at the time of insertion. Standard criteria
      were applied to all patients for diagnosis of CSF infection. RESULTS: A total of
      215 patients were included, 16 (7.4%) of whom developed CSF infection. Antibiotic
      prophylaxis for ICPM placement was administered to 63% of infected and 59% of non
      infected patients. Vancomycin (60%) and cefazolin (34%) were used most often.
      Sixty per cent (6/16) of patients who developed infection and 45% (53/199) of
      those without CSF infection received their first antibiotic dose within the 2
      hours before ICPM insertion. Risk factors for CSF infection included duration of
      monitoring greater than 5 days (RR 4.0 (1.3-11.9)); presence of ventriculostomy
      (RR 3.4 (1.0-10.7)); CSF leak (RR 6.3 (1.5-27.4)); concurrent systemic infection
      (RR 3.4 (1.2-9.5)); or serial ICPM (RR 4.9 (1. 7-13.8)). CONCLUSIONS:
      Administration of antibiotics to patients before or at the time of ICPM placement
      did not decrease the incidence of CSF infection. Patients found to be at greater
      risk for infection at our institution included duration of ICPM greater than 5
      days, use of ventricular catheter, CSF leak, concurrent systemic infection, or
      serial ICPM.

PMID- 10945815
TI  - Primary diffuse leptomeningeal gliomatosis: unusual MRI with non-enhancing
      nodular lesions on the cerebellar surface and spinal leptomeningeal enhancement.
AB  - A 28 year old man presented with a 1 month history of symptoms of intracranial
      hypertension. Examination showed bilateral papilloedema and meningeal signs.
      Magnetic resonance imaging showed nodular lesions on the cerebellar and pontine
      surface and thickening of the thoracic spinal leptomeninges. Throughout the
      course of the disease, contrast enhancement was detected in the spinal
      leptomeninges but not intracranially. Primary diffuse leptomeningeal gliomatosis
      (PDLG) was diagnosed by biopsy and later confirmed on necropsy. The present case
      is remarkable for the nodular superficial cerebellar lesions and the absence of
      intracranial contrast enhancement of the leptomeninges.

PMID- 10945816
TI  - Spatial memory impairment in patients after tumour resection: evidence for a
      double dissociation.
AB  - Human spatial memory can be divided into multiple, partly separate cognitive
      processes. In this study, object location memory was studied using a set of tasks
      that assessed three different spatial memory aspects: positional memory, object
      location binding, and a combined process. Also, maze learning and spatial span
      memory were measured. Ten patients who had undergone intracranial tumour
      resection participated, and their individual results were compared with control
      data from 24 healthy subjects. Four patients showed selective spatial memory
      impairments; two patients were impaired at positional memory, and two other
      patients were impaired on object location binding and the combined process. This
      double dissociation provides further evidence for the notion that object location
      memory is not a unitary system, but consists of at least two separate mechanisms.
      In addition, spatial memory problems were predominantly present in the patients
      with lesions in either the right hemisphere or in the parietal lobe. These
      results are in agreement with previous findings on the involvement of the right
      hemisphere and the posterior parietal cortices in spatial processing.

PMID- 10945817
TI  - Late adult onset chorea with typical pathology of Hallervorden-Spatz syndrome.
AB  - Senile chorea is a well recognised but poorly understood clinical entity
      characterised by a slowly progressive, generalised chorea in elderly people
      without mental deterioration or a clear underlying cause. The Hallervorden-Spatz
      syndrome is typically thought of as a paediatric condition with extrapyramidal
      features and dementia. However, it has been described in adults usually
      presenting with parkinsonism plus dementia. An elderly woman with slowly
      progressive chorea without dementia was found at postmortem to have the
      pathological features originally described by Hallervorden and Spatz. This
      association has not previously been reported.

PMID- 10945818
TI  - Management of intracranial bleeding associated with anticoagulation: balancing
      the risk of further bleeding against thromboembolism from prosthetic heart
      valves.
AB  - Mechanical heart valves are associated with a risk of thromboembolism and
      anticoagulation is generally recommended. However, this is inevitably associated
      with a risk of intracranial bleeding. The case of a patient who sustained an
      intracranial bleed while taking warfarin for a prosthetic aortic valve and a
      further two intracranial bleeds while on heparin as an inpatient is discussed and
      the literature on the management of intracranial haemorrhage in patients on
      warfarin with prosthetic valves is reviewed.

PMID- 10945820
TI  - Neurosurgery. The scientific basis of clinical practice. Third edition

PMID- 10945819
TI  - Vanishing Balo-like lesions in multiple sclerosis.

PMID- 10945821
TI  - Parkinson's disease: A self-help guide for patients and their carers

PMID- 10945822
TI  - Neuroimaging, volumes 1 and 2

PMID- 10945823
TI  - Prevention of ischemic stroke

PMID- 10945824
TI  - The genesis of neuroscience

PMID- 10945825
TI  - Cell death and diseases of the nervous system

PMID- 10945826
TI  - Phospholipase A(2)s in cell injury and death.
AB  - Phospholipase A(2)s (PLA(2)s) represent a family of esterases that hydrolyze the
      sn-2 ester bond in phospholipids, releasing free fatty acids and
      lysophospholipids. PLA(2)s are important in the signaling of several cellular
      processes and are known to play a significant role in inflammation. Studies also
      show that PLA(2)s are modulators of drug-, chemical-, and ischemia/reperfusion
      induced cellular injury. The role of PLA(2)s in apoptosis and oncosis depends
      upon the PLA(2) isoform, the cell type, and the stimulus of injury. The purpose
      of this review is to discuss the functions of iPLA(2), cPLA(2) and sPLA(2)
      isoforms in oncosis and apoptosis, including oxidant-induced and receptor
      mediated cell death. In addition, the measurement and modulation of PLA(2) is
      discussed.

PMID- 10945827
TI  - Neuroprotective effects of LY379268, a selective mGlu2/3 receptor agonist:
      investigations into possible mechanism of action in vivo.
AB  - The mechanisms underlying the neuroprotective effects of the group II
      metabotropic glutamate receptor (mGluR) agonist LY379268 were investigated in a
      gerbil model of global ischemia. LY379268 (10 mg/kg i.p.) 30 or 60 min after 5
      min bilateral carotid artery occlusion (BCAO) attenuated the ischemia-induced
      hyperactivity and provided protection in the CA1 hippocampal cells. This
      neuroprotective effect was maintained (P <.001) when histological analysis was
      performed 14 and 28 days after BCAO. Furthermore, 24- or 48-h pretreatment with
      LY379268, 10 mg/kg i.p., before 5-min BCAO markedly reduced (P <.001 and P <.05,
      respectively) the damage to CA1 hippocampal neurons. This result is consistent
      with the induction of neuroprotective factors or a very long brain half-life. To
      study the possible induction of neuroprotective factors as contributing to this
      action of LY379268, brains were examined for expression of neurotrophic factors.
      Results indicated that LY379268 (10 mg/kg i.p.) failed to alter the expression of
      transforming growth factor-beta, brain-derived neurotrophic factor, nerve growth
      factor, and basic fibroblast growth factor in the hippocampal regions of brains
      taken from gerbils sacrificed at 6, 24, 72, and 120 h postinjection. The new
      group II mGlu antagonist, LY341495, administered 1 h before 5-min BCAO,
      attenuated the neuroprotective effect of LY379268 administered 24 h before 5-min
      BCAO. Complementary pharmacokinetic studies showed that a significant receptor
      active concentration persisted in the brain 24 h after LY379268 10 mg/kg i.p. We
      conclude that group II mGluR occupancy, rather than induction of neuroprotective
      factors, explains the long-lasting neuroprotective effect of LY379268 in the
      gerbil model of global ischemia.

PMID- 10945828
TI  - Cloning and cellular localization of the rat mast cell 78-kDa protein
      phosphorylated in response to the mast cell "stabilizer" cromolyn.
AB  - Disodium cromoglycate (cromolyn) inhibits mast cell secretion, but its mechanism
      has not been elucidated. One possibility is the phosphorylation of a 78-kDa mast
      cell protein, two fragments of which are homologous to moesin, a member of the
      ezrin, radixin, moesin family. These proteins appear to be involved in signal
      transduction by regulating functional associations between the cell surface and
      the cytoskeleton. Moesin cDNA was cloned from rat basophil leukemia cells, which
      are similar to mucosal mast cells, and polyclonal antiserum was prepared against
      recombinant moesin expressed in Escherichia coli. Moesin phosphorylated in mast
      cells treated with cromolyn shifted from the soluble to the precipitable fraction
      and associated with Sepharose-linked beta-actin. Recombinant moesin also
      associated with Sepharose-linked beta-actin, and so did purified RBL moesin, but
      only if the latter was first denatured. Moesin thus appears to have actin binding
      sites that are not exposed under normal conditions but may become available by in
      vivo phosphorylation or by denaturation. Immunocytochemistry using confocal
      microscopy showed moesin to be primarily localized on the inner aspect of the
      plasma membrane and around secretory granules. Double immunocytochemistry for
      moesin and actin colocalized them in most areas. Ultracryoimmunoelectron
      microscopy to preserve the antigenicity of moesin identified the protein close to
      the plasma and secretory granule membranes. Cromolyn appeared to induce
      clustering of moesin around secretory granules. It is hypothesized that
      conformational changes of moesin, regulated by phosphorylation/dephosphorylation,
      may lead to positional rearrangements with respect to the membrane/cytoskeleton
      that could possibly regulate mast cell secretion.

PMID- 10945829
TI  - The effect of berberine chloride on experimental colitis in rats in vivo and in
      vitro.
AB  - Berberine is an isoquinoline alkaloid with multiple pharmacological actions,
      including anti-inflammatory activity. The aims of this study were to examine the
      effect of berberine on the mucosal healing process and to investigate whether
      berberine can inhibit the increased production of interleukin-8 in
      trinitrobenzene sulfonic acid-induced colitis in rats. Berberine was administered
      orally for 3 days or 1 week at a dosage of 7.5 or 15 mg/kg/day. Tissue damage
      scores, body weight, colon wet weight, and colon wall thickness were measured,
      and myeloperoxidase activity in colon tissue was also examined. Histological
      lesions, morphological damage, and myeloperoxidase activity were reduced after 1
      week of treatment with berberine at a dosage of 15 mg/kg/day. Furthermore, 1 week
      after trinitrobenzene sulfonic acid treatment, the production of interleukin-8 by
      cultured rectal mucosa or cardiac blood mononuclear cells with or without
      stimulation of lipopolysaccharide for 24 h was also analyzed by enzyme-linked
      immunosorbent assay. Cardiac blood mononuclear cells and rectal mucosa of normal
      rats produced substantial amounts of interleukin-8, which increased strikingly
      with the stimulation of lipopolysaccharide. Cardiac blood mononuclear cells and
      rectal mucosa of trinitrobenzene sulfonic acid-treated rats secreted more
      interleukin-8 than those of normal rats. The addition of berberine with a
      concentration of 10(-5) M to the culture media resulted in an inhibition of
      interleukin-8 production of rectal mucosa.

PMID- 10945830
TI  - Efflux of dietary flavonoid quercetin 4'-beta-glucoside across human intestinal
      Caco-2 cell monolayers by apical multidrug resistance-associated protein-2.
AB  - Although there is strong evidence to suggest that flavonoid consumption is
      beneficial to human health, the extent to which flavonoids are absorbed and the
      mechanisms involved are controversial. Contrary to common dogma, we previously
      demonstrated that quercetin 4'-beta-glucoside, the predominant form of the most
      abundant dietary flavonoid, quercetin, was not absorbed across Caco-2 cell
      monolayers. The aim of this study was to test the hypothesis that a specific
      efflux transporter is responsible for this lack of absorption. Transport of
      quercetin 4'-beta-glucoside, alone or with inhibitors, was examined with Caco-2
      cell monolayers. In addition, subcellular localization of the multidrug
      resistance-associated proteins MRP1 and MRP2 was examined by immunofluorescent
      confocal microscopy. Efflux of quercetin 4'-beta-glucoside, a saturable process,
      was not altered by verapamil, a P-glycoprotein inhibitor, but was competitively
      inhibited by MK-571, an MRP inhibitor. These data in combination with
      immunofluorescent localization of MRP2 to the apical membrane support a role for
      MRP2 in the intestinal transcellular efflux of quercetin 4'-beta-glucoside. These
      results suggest a role for MRP2 in the transport of a new class of agents,
      dietary glucosides.

PMID- 10945831
TI  - Cellular uptake of dietary flavonoid quercetin 4'-beta-glucoside by sodium
      dependent glucose transporter SGLT1.
AB  - Although it has been suggested that the intestinal glucose transporter may
      actively absorb dietary flavonoid glucosides, there is a lack of direct evidence
      for their transport by this system. In fact, our previous studies with the human
      Caco-2 cell model of intestinal absorption demonstrated that a major dietary
      flavonoid, quercetin 4'-beta-glucoside, is effluxed by apically expressed
      multidrug resistance-associated protein-2, potentially masking evidence for
      active absorption. The objective of this study was to test the hypothesis that
      quercetin 4'-beta-glucoside is a substrate for the intestinal sodium-dependent D
      glucose cotransporter SGLT1. Cellular uptake of quercetin 4'-beta-glucoside was
      examined with Caco-2 cells and SGLT1 stably transfected Chinese hamster ovary
      cells (G6D3 cells). Although quercetin 4'-beta-glucoside is not absorbed across
      Caco-2 cell monolayers, examination of the cells by indirect fluorescent
      microscopy as well as by HPLC analysis of cellular content revealed cellular
      accumulation of this glucoside after apical loading. Consistent with previous
      observations, the accumulation of quercetin 4'-beta-glucoside in both Caco-2 and
      G6D3 cells was markedly enhanced in the presence of multidrug resistance
      associated protein inhibition. Uptake of quercetin 4'-beta-glucoside was greater
      in SGLT1-transfected cells than in parental Chinese hamster ovary cells. Uptake
      of the glucoside by Caco-2 and G6D3 cells was sodium-dependent and was inhibited
      by the monovalent ionophore nystatin. In both Caco-2 and G6D3 cells, quercetin 4'
      beta-glucoside uptake was inhibited by 30 mM glucose and 0.5 mM phloridzin. These
      results demonstrate for the first time that quercetin 4'-beta-glucoside is
      transported by SGLT1 across the apical membrane of enterocytes.

PMID- 10945832
TI  - Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine,
      acyclovir, and other antiviral nucleoside analogs.
AB  - Organic anion transporter 1 (OAT1) is a p-aminohippurate/dicarboxylate exchanger
      that plays a primary role in the tubular secretion of endogenous and exogenous
      organic anions. OAT1 is located in the basolateral membrane of the proximal
      tubular cells and mediates the uptake of various organic anions from the
      peritubular fluid. In this study, we investigated the transport of antiviral
      nucleoside analogs via rat OAT1 (rOAT1) using a heterologous expression system in
      Xenopus laevis oocytes. Oocytes injected with rOAT1 cRNA showed significantly
      higher uptake of zidovudine (AZT) and acyclovir (ACV) than control oocytes. rOAT1
      mediated uptake of AZT and ACV was probenecid-sensitive and increased by the
      outwardly directed gradient of glutarate. The affinity of rOAT1 for AZT and ACV
      was determined to be 68 and 242 microM, respectively. Five other antiviral agents
      that we studied (zalcitabine, didanosine, lamivudine, stavudine, and
      trifluridine) were also shown to be transported by rOAT1, whereas foscarnet, a
      phosphate analog, was not. The aforementioned nucleoside analogs lack a typical
      anionic group and are not very hydrophobic. This study demonstrates extension of
      the substrate spectrum of rOAT1 and provides a molecular basis for the
      pharmacokinetics of antiviral nucleoside analogs.

PMID- 10945833
TI  - The effects of high-dose methamphetamine in the aging rat: differential
      reinforcement of low-rate 72-s schedule behavior and neurochemistry.
AB  - High-dose methamphetamine (METH) causes damage to the dopamine and serotonin
      neurons in the brains of laboratory animals. The purpose of this report was to
      determine the long-term consequences of high-dose METH treatment on behavior and
      neurochemistry. Rats were trained on the differential reinforcement of low-rate
      72-s (DRL 72-s) schedule of reinforcement. Twelve weeks after training began (age
      23 weeks), they received one or three high-dose METH regimens. Each regimen
      consisted of four injections of 15 mg/kg, at 2-h intervals. Each regimen was
      separated by 7 weeks. A second group received METH treatment at age 23 weeks, but
      behavioral training was not initiated until the rats reached age 60 weeks. A
      third group received METH treatment without behavioral training. DRL behavior
      showed mild impairments 3 to 18 weeks after the onset of treatment; the
      impairments did not persist into middle age. At age 70 weeks, serotonin
      concentrations were decreased in somatosensory cortex, occipital cortex, and
      hippocampus but not in other subcortical structures. Serotonin tissue
      concentrations were enhanced in septum and striatum but only in rats receiving
      three regimens and behavioral training. Dopamine was not depleted at age 70
      weeks. In three additional groups, one, two, or three METH regimens were
      administered, and tissue concentrations were measured 6 weeks after the last
      treatment (corresponding to the times of the behavioral test blocks in the DRL
      experiments). Serotonin depletions were noted in cortex, hippocampus, amygdala,
      and striatum but not in septum, hypothalamus, nucleus accumbens/olfactory
      tubercle, or ventral midbrain. Dopamine was decreased in striatum and septum but
      not in nucleus accumbens/olfactory tubercle, amygdala, hypothalamus, or ventral
      midbrain. DRL 72-s schedule impairments are attributed to serotonin depletions.
      Three METH regimens did not result in greater behavioral or neurochemical
      deficits than one regimen.

PMID- 10945834
TI  - Rebamipide inhibits neutrophil adhesion to hypoxia/reoxygenation-stimulated
      endothelial cells via nuclear factor-kappaB-dependent pathway.
AB  - This study was designed to determine whether rebamipide can inhibit neutrophil
      adhesion to human umbilical vein endothelial cells (HUVECs) stimulated with 1 h
      of hypoxia followed by 4 h of reoxygenation (H/R). Furthermore, to define the
      action mechanisms, we determined the effect of rebamipide on the surface
      expression of endothelial cell adhesion molecules E-selectin, P-selectin, and
      intercellular adhesion molecule-1 (ICAM-1) on H/R-stimulated HUVECs. Under
      resting conditions, both E-selectin and P-selectin were not expressed on the
      surface of HUVECs in contrast to ICAM-1, which was constitutively expressed.
      After stimulation with H/R, HUVECs showed an enhanced neutrophil adhesivity in
      association with an increased surface expression of E-selectin and P-selectin
      with a marginal increase in ICAM-1 expression. In parallel, the increased nuclear
      translocation of nuclear factor-kappaB in H/R-stimulated HUVECs was monitored by
      electrophoretic mobility shift assay (adjusted volume units, 11.9 +/- 2.5 x 10(4)
      counts x mm(2) in unstimulated cells versus 24.2 +/- 3.0 x 10(4) counts x mm(2)
      in H/R-stimulated cells). Rebamipide suppressed the surface expression of E
      selectin and P-selectin with a subsequent inhibition of neutrophil adhesion to
      H/R-stimulated HUVECs. In line with these results, rebamipide (100, 300, and 1000
      microM) inhibited H/R-induced nuclear translocation of nuclear factor-kappaB in a
      concentration-dependent manner. Taken together, this study demonstrates that
      rebamipide inhibits neutrophil adhesion to HUVECs by a mechanism involving
      inhibition of transcription-dependent surface expression of E-selectin and P
      selectin in H/R-stimulated endothelial cells.

PMID- 10945836
TI  - Actions of the anticonvulsant remacemide metabolite AR-R12495AA on afferent
      evoked spinal synaptic transmission in vitro and on models of acute and chronic
      inflammation in the rat.
AB  - The effects of the anticonvulsant remacemide [(+/-)-2-amino-N-(1-methyl-1,2
      diphenylethyl)-acetamide hydrochloride] and its metabolite AR-R12495AA [(+/-)-1
      methyl-1, 2-diphenylethylamine-monohydrochloride] on primary afferent synaptic
      transmission were assessed in the young rat spinal cord in vitro. Stimulation of
      dorsal roots at A- and C-afferent intensity elicited a dorsal root-evoked ventral
      root potential (DR-VRP) with a slowly decaying phase. Repetitive stimuli (2 Hz)
      produced summation of slow potentials and a cumulative ventral root
      depolarization (CVRD), a form of wind-up. Remacemide and AR-R12495AA antagonized
      the DR-VRP slow peak t(1/2) decay and slow phase total duration at drug
      concentration of > or =25 microM. AR-R12495AA was approximately 2-fold more
      potent than remacemide. The most potent action was against the slow phase
      duration with IC(50) values of 157 and 60 microM for remacemide and AR-R12495AA,
      respectively. Both drugs at concentrations of > or =100 microM attenuated the DR
      VRP fast peak amplitude (IC(50) = 253 and 142 microM, respectively). The
      amplitude of CVRD was reduced by remacemide and AR-R12495AA (IC(50) = 195 and 111
      microM, respectively). MK-801 reduced DR-VRP fast peak amplitude (IC(50) = 58
      microM), slow peak t(1/2) decay (IC(50) = 60 microM), slow phase duration (IC(50)
      = 50 microM), and CVRD amplitude (IC(50) = 91 microM). In behavioral studies, AR
      R12495AA (i.p.) reduced the mechanical hyperalgesia and paw swelling that
      followed hind paw injection of carrageenan or Freund's complete adjuvant. These
      electrophysiological and behavioral data indicate further studies should be
      conducted on the efficacy of remacemide and AR-R12495AA as putative analgesics.

PMID- 10945835
TI  - Potentiation of penile tumescence by T-1032, a new potent and specific
      phosphodiesterase type V inhibitor, in dogs.
AB  - We examined the mechanism underlying the potentiation of penile tumescence by
      methyl 2-(4-aminophenyl)-1, 2dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4, 5
      trimethoxyphenyl)3-isoquinoline carboxylate sulfate (T-1032), a new potent and
      selective phosphodiesterase type V inhibitor. In vivo, pelvic nerve stimulation
      induced a penile tumescence together with increase of total nitric oxide
      metabolite levels within the corpus cavernosa of anesthetized dogs. Intravenous
      (1-100 microg/kg) and intraduodenal (3, 30, 300 microg/kg) treatment with T-1032
      dose dependently potentiated the tumescence. The potency of T-1032 was equivalent
      to that of sildenafil. T-1032 did not influence the intracavernous pressure when
      the pelvic nerve stimulation was absent. The potentiation of tumescence was more
      pronounced by intracavernous than i.v. injection. Intracavernous N(G)-nitro-L
      arginine, a nitric-oxide synthase inhibitor, but not N(G)-nitro-D-arginine
      diminished the effects of T-1032 on the tumescence. Furthermore, i.v. T-1032
      augmented the tumescence induced by sodium nitroprusside (SNP) but not by
      vasoactive intestinal polypeptide (VIP). In vitro, in isolated preparations of
      canine corpus cavernosum precontracted with phenylephrine, SNP (0. 01-100 microM)
      and VIP (0.01-1 microM) produced a dose-dependent relaxation accompanied by an
      increase in cGMP and cAMP levels, respectively. T-1032 augmented the relaxation
      induced by SNP but not by VIP. These data suggest that oral treatment with T-1032
      has potential to improve erectile dysfunction through the inhibition of
      phosphodiesterase type V in the smooth muscles of corpus cavernosa.

PMID- 10945837
TI  - Differential effects of 4-chloro-m-cresol and caffeine on skinned fibers from rat
      fast and slow skeletal muscles.
AB  - Contractile responses to 4-chloro-m-cresol (4-CmC) were tested in saponin- and
      Triton X-100-skinned fibers from soleus and edl (extensor digitorum longus)
      muscles of adult rats and compared with those to caffeine. The testing of
      different concentrations of 4-CmC on saponin-skinned fibers showed that 4-CmC
      induced a dose-dependent caffeine-like transient contractile response in edl and
      soleus due to an activation of the ryanodine receptor. Both types of skeletal
      muscles showed a 10 to 20 times lower 4-CmC threshold concentration and EC(50)
      value (concentration providing 50% of the maximal 4-CmC contracture) than for
      caffeine. The results indicate that edl is more sensitive than soleus to 4-CmC
      and that this difference in sensitivity is more marked than with caffeine.
      Furthermore, an increase in cytosolic Ca(2+) activity induced a more marked shift
      of dose-response curves toward lower concentrations for 4-CmC than caffeine.
      Experiments conducted on Triton X-100-skinned fibers showed that in both muscles,
      4-CmC decreased in a dose-dependent manner the Ca(2+)-activated force of
      contractile apparatus, particularly in edl. Furthermore, the tension pCa curves
      indicated that 4-CmC induced a dose-dependent sensitizing (soleus) or
      desensitizing (edl) effect on the Ca(2+) sensitivity of myofibrils. These results
      indicate that edl and soleus contractile responses can be discriminated with 4
      CmC instead of caffeine and that care must be taken in interpreting results
      because muscular pathology could be due in part to an increase in intracellular
      Ca(2+).

PMID- 10945838
TI  - Pharmacokinetics and metabolism of the methotrexate metabolite 2, 4-diamino-N(10)
      methylpteroic acid.
AB  - The novel methotrexate (MTX) rescue agent carboxypeptidase-G(2) (CPDG(2))
      converts >98% of plasma MTX to 2, 4-diamino-N(10)-methylpteroic acid (DAMPA) and
      glutamate in patients with MTX-induced renal failure and delayed MTX excretion.
      DAMPA is eliminated more rapidly than MTX in these patients, suggesting nonrenal
      elimination. The pharmacokinetics and metabolism of DAMPA were studied in four
      nonhuman primates with reverse-phase HPLC with UV, photodiode array detection,
      and mass spectroscopy. The mean peak plasma DAMPA concentration was 51 microM and
      the plasma disposition was described by a three-compartment open model with first
      order elimination. The mean clearance of DAMPA was 1.9 l/kg/h and the mean
      terminal half-life was 51 min. Forty-six percent of the dose was excreted in the
      urine as parent compound. Three DAMPA metabolites, hydroxy-DAMPA, DAMPA
      glucuronide, and hydroxy-DAMPA-glucuronide, were identified in plasma and urine.
      These metabolites also were identified in plasma from patients who received
      CPDG(2) as an MTX rescue agent. The cytotoxicity of DAMPA and its effect on MTX
      cytotoxicity were assessed in the Molt-4 human leukemic cell line. DAMPA was not
      cytotoxic and did not significantly alter the cytotoxicity of MTX. In nonhuman
      primates metabolism of DAMPA is a major route of DAMPA elimination, and
      metabolism underlies the more rapid elimination of DAMPA versus MTX in patients
      with MTX-induced renal dysfunction after administration of CPDG(2).

PMID- 10945839
TI  - Antagonism of the discriminative stimulus effects of positive gamma-aminobutyric
      acid(A) modulators in rhesus monkeys discriminating midazolam.
AB  - The extent to which individual subtypes of benzodiazepine receptors are
      functionally independent has not been elucidated in vivo. This study used
      apparent pA(2) analysis to test the hypothesis that a single receptor subtype
      mediates the discriminative stimulus effects of midazolam, triazolam, and
      diazepam, three positive gamma-aminobutyric acid(A) (GABA(A)) modulators. Four
      rhesus monkeys discriminated 0.56 mg/kg midazolam from vehicle under a fixed
      ratio 5 schedule of stimulus-shock termination. Midazolam, triazolam, and
      diazepam increased responding on the midazolam-appropriate lever. The neutral
      GABA(A) modulator flumazenil shifted dose-effect curves for triazolam and
      diazepam to the right, and the negative GABA(A) modulators Ro 15-4513 and ethyl
      beta-carboline-3-carboxylate (beta-CCE) shifted dose-effect curves for midazolam
      and triazolam to the right. Slopes of Schild plots for flumazenil and Ro 15-4513
      conformed to unity. The apparent pA(2) values were 7.41 and 7.69 for flumazenil
      in combination with triazolam and diazepam, respectively, and 7.53 and 6.88 for
      Ro 15-4513 in combination with midazolam and triazolam, respectively. The slope
      of the Schild plot for beta-CCE in combination with midazolam deviated from
      unity. Slopes of Schild plots obtained with flumazenil and Ro 15-4513 support the
      notion that a single benzodiazepine receptor subtype mediates the effects of
      midazolam, triazolam, or diazepam. The similarity in apparent pA(2) values for
      flumazenil in combination with triazolam and diazepam or for Ro 15-4513 in
      combination with midazolam and triazolam suggests that the same subtype mediates
      the effects of these positive modulators. In contrast, beta-CCE and midazolam do
      not appear to interact in a simple, competitive manner.

PMID- 10945840
TI  - Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a
      rat model of catamenial epilepsy.
AB  - Perimenstrual catamenial epilepsy, the exacerbation of seizures in association
      with menstruation, may in part be due to withdrawal of the progesterone
      metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous
      anticonvulsant neurosteroid that is a positive allosteric modulator of gamma
      aminobutyric acid(A) receptors. Neurosteroid replacement is a potential approach
      to therapy, but natural neurosteroids have poor bioavailability and may be
      converted to metabolites with undesired progestational activity. The synthetic
      neuroactive steroid ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20
      one) is an orally active analog of allopregnanolone that is not converted to the
      hormonally active 3-keto form. To assess the potential of ganaxolone in the
      treatment of catamenial seizure exacerbations, a state of persistently high serum
      progesterone (pseudopregnancy) was induced in 26-day-old female rats with
      gonadotropins, and neurosteroids were withdrawn on postnatal day 39 with
      finasteride, a 5alpha-reductase inhibitor that blocks the conversion of
      progesterone to allopregnanolone. Finasteride treatment during pseudopregnancy
      results in a reduction in the threshold for pentylenetetrazol seizures. During
      this state of enhanced seizure susceptibility, there was a 3-fold increase in the
      anticonvulsant potency of ganaxolone (control ED(50) = 3.5 mg/kg; withdrawn = 1.2
      mg/kg) without a change in the potency for induction of motor toxicity in the
      rotarod test. The plasma concentrations of ganaxolone did not differ
      significantly in control and withdrawn animals; the estimated plasma
      concentrations of ganaxolone producing 50% seizure protection were approximately
      500 and approximately 225 ng/ml in control and withdrawn rats, respectively.
      Unlike ganaxolone, neurosteroid withdrawal was associated with a decrease in the
      anticonvulsant potency of diazepam (control ED(50) = 1.9 mg/kg; withdrawn = 4.1
      mg/kg) and valproate (control ED(50) = 279 mg/kg; withdrawn = 460 mg/kg). The
      enhanced anticonvulsant potency of ganaxolone after neurosteroid withdrawal
      supports the use of ganaxolone as a specific treatment for perimenstrual
      catamenial epilepsy.

PMID- 10945841
TI  - Activation of cytochrome P450 gene expression in the rat brain by phenobarbital
      like inducers.
AB  - Oxidative biotransformation, coupled with genetic variability in enzyme
      expression, has been the focus of hypotheses interrelating environmental and
      genetic factors in the etiology of central nervous system disease processes.
      Chemical modulation of cerebral cytochrome P450 (P450) monooxygenase expression
      character may be an important determinant of in situ metabolism, neuroendocrine
      homeostasis, and/or central nervous system toxicity resulting from exposure to
      neuroactive drugs and xenobiotic substances. To examine the capacity of the rat
      brain to undergo phenobarbital (PB)-mediated induction, we developed reverse
      transcription-polymerase chain reaction methods and evaluated the effects of
      several PB-like inducers on P450 and microsomal epoxide hydrolase gene
      expression. Animals treated i.p. with four daily doses of PB demonstrated
      markedly induced levels of CYP2B1, CYP2B2, and CYP3A1 mRNA in the striatum and
      cerebellum. In contrast, 1 or 2 days of PB treatment resulted in unchanged or
      even slightly decreased levels of CYP2B1 and CYP2B2 in the brain, although the
      latter treatments produced marked induction of the corresponding genes in the
      liver. Only slight increases in epoxide hydrolase RNA levels resulted in brains
      of PB-treated animals. Substantial activation of cerebral CYP2B1, CYP2B2, and
      CYP3A1 mRNA levels also resulted when animals were treated with the neuroactive
      drugs diphenylhydantoin and amitryptiline, and with the potential PB-like
      xenobiotic inducers trans-stilbene oxide and diallyl sulfide, whereas
      dichlorodiphenyltrichloroethane was less efficacious. Although the time course of
      the induction response is delayed in brain relative to that required for the
      liver, these results clearly establish that brain P450s are markedly PB
      inducible.

PMID- 10945842
TI  - Aryloxypropanolamine and catecholamine ligand interactions with the beta(1)
      adrenergic receptor: evidence for interaction with distinct conformations of
      beta(1)-adrenergic receptors.
AB  - Pharmacological responses to aryloxypropanolamines were examined in cells
      expressing rat or human beta(1)-adrenergic receptors (ARs) using adenylyl cyclase
      assays. The aryloxypropanolamines CGP 12177 and LY 362884, originally developed
      as beta(3)-AR agonists, were found to stimulate the beta(1)-AR. Interestingly,
      both CGP 12177 and LY 362884 exhibited an anomalous biphasic effect on beta(1)
      AR. Low concentrations of either CGP 12177 or LY 362884 potently blocked
      isoproterenol-induced stimulation of beta(1)-AR, whereas higher concentrations of
      these compounds stimulated the beta(1)-AR. The unusual interaction of these
      aryloxypropanolamine ligands with the beta(1)-AR was further characterized using
      beta-AR antagonists. Activation of beta(1)-AR by CGP 12177 or LY 362884 was
      observed to be significantly more resistant to blockade by beta-AR antagonists
      compared with activation by catecholamines. These results suggest that
      catecholamines and aryloxypropanolamines interact with distinct active
      conformations of the beta(1)-AR: a state that is responsive to catecholamines and
      is blocked with high affinity by CGP 12177 and LY 362884, and a novel state that
      is activated by aryloxypropanolamines but is resistant to blockade by standard
      beta-AR antagonists. Moreover, dependence of antagonist affinity on agonist
      structure is unprecedented, and its implications on the use of beta-AR agonists
      such as CGP 12177 in receptor classification are discussed.

PMID- 10945844
TI  - G(1) Phase growth arrest and induction of p21(Waf1/Cip1/Sdi1) in IB3-1 cells
      treated with 4-sodium phenylbutyrate.
AB  - 4-Sodium phenylbutyrate (4-PBA) has been used for many years in the treatment of
      urea cycle defects and has recently been studied as a chemotherapeutic agent for
      certain malignancies. 4-PBA has been shown to cause growth arrest, cellular
      differentiation, and apoptosis in certain malignant cells. Recently, it was shown
      that IB3-1 cells (a cystic fibrosis cell line, Delta508/W128X) treated with 4-PBA
      demonstrated a partial correction of the cystic fibrosis chloride channel defect.
      We were interested in evaluating the effect of 4-PBA on cell growth and cell
      cycle regulation in IB3-1 cells treated with 2 to 10 mM concentrations. We found
      that cells treated with 2 mM concentrations of 4-PBA for 96 h underwent a
      significant decrease in cell growth (P <.007). Using flow cytometry, we were able
      to demonstrate that growth arrest occurred at the G(1) phase of the cell cycle.
      This was detected as early as 24 h in IB3-1 cells treated with 5 mM 4-PBA (P
      <.03). Furthermore, the percentage of IB3-1 cells with less than a 2N DNA content
      increased with higher concentrations of 4-PBA, although this was not associated
      with an increase in apoptosis. Finally, p21(Waf1/Cip1/Sdi1) protein levels were
      induced in IB3-1 cells receiving 2 and 5 mM concentrations of 4-PBA as early as
      24 h of exposure, suggesting that G(1) phase growth arrest in IB3-1 cells treated
      with 4-PBA is regulated through the p21(Waf1/Cip1/Sdi1) pathway.

PMID- 10945843
TI  - Methocinnamox is a potent, long-lasting, and selective antagonist of morphine
      mediated antinociception in the mouse: comparison with clocinnamox, beta
      funaltrexamine, and beta-chlornaltrexamine.
AB  - The irreversible mu-opioid antagonists beta-funaltrexamine (beta-FNA) and beta
      chlornaltrexamine (beta-CNA) are important pharmacological tools but have a kappa
      agonist activity and, in the latter case, low selectivity. This work examines
      whether clocinnamox (C-CAM) and the newer analog, methocinnamox (M-CAM),
      represent improved long-lasting antagonists for examining mu-opioid-mediated
      effects in vivo. beta-FNA, beta-CNA, C-CAM, and M-CAM were compared after
      systemic administration in mice and in vitro. beta-FNA and beta-CNA were
      effective agonists in the writhing assay, reversible by the kappa-antagonist
      norbinaltorphimine. Neither C-CAM nor M-CAM had agonist activity in vivo. M-CAM
      was devoid of agonist action at cloned opioid receptors. All four compounds
      depressed the dose-effect curve for the mu-agonist morphine in the warm-water
      tail-withdrawal test 1 h after administration; at 48 h, recovery was evident. In
      the writhing assay, the dose-effect curve for morphine was shifted in a parallel
      fashion in the order M-CAM >> C-CAM > beta-CNA > or = beta-FNA. In comparison
      with their ability to shift the dose-effect curve for bremazocine (kappa) and
      BW373U86 (delta), beta-CNA was the least mu-selective, followed by C-CAM < beta
      FNA < M-CAM. M-CAM (1.8 mg/kg) produced a 74-fold increase in the ED(50) of
      morphine while showing no effect on bremazocine or BW373U86 dose-response curves.
      In binding assays, C-CAM and M-CAM were 8-fold selective for mu- over kappa
      receptors, whereas beta-FNA and beta-CNA were mu/delta-, but not mu/kappa,
      selective. However, ex vivo binding assays confirmed the mu-receptor selectivity
      of M-CAM. M-CAM is thus a potent, long-lasting, and specific antagonist at mu
      receptors in vivo that lacks confounding agonist actions.

PMID- 10945845
TI  - Nephroprotective effect of treatment with calcium channel blockers in
      spontaneously hypertensive rats.
AB  - The influence of hypertension and of treatment with some dihydropyridine-type
      Ca(2+) channel blockers and with the nondihydropyridine-type vasodilator
      hydralazine on the morphology of kidney was investigated in 26-week-old
      spontaneously hypertensive rats (SHR) and in age-matched Wistar-Kyoto rats.
      Fourteen-week-old SHR were treated for 12 weeks with a nonhypotensive dose of
      lercanidipine or with equihypotensive doses of lercanidipine, manidipine,
      nicardipine, and hydralazine. In control SHR, systolic pressure values were
      significantly higher in comparison with Wistar-Kyoto rats. Treatment with the low
      dose of lercanidipine did not reduce systolic blood pressure in SHR, whereas the
      higher dose of lercanidipine or other compounds tested significantly decreased
      systolic pressure values. Glomerular hypertrophy accompanied by signs of
      glomerulosclerosis, increase of mesangial cells, and convoluted tubules
      degeneration were observed in control SHR. Hypotensive doses of Ca(2+)
      antagonists countered glomerular injury, the increase of mesangial cells, the
      reduction of capsular space, and tubular degeneration. Hydralazine, in spite of
      its hypotensive activity, displayed a slight nephroprotective action. The
      nonhypotensive dose of lercanidipine countered in part glomerular injury,
      narrowing of capsular space, and tubular degeneration, and decreased mesangial
      cell augmentation in SHR. These results suggest that treatment with
      dihydropyridine-type Ca(+2) antagonists counters hypertensive glomerular and
      tubular changes occurring in SHR. The demonstration of nephroprotection by the
      nonhypotensive dose of lercanidipine suggests that the renal effects of the
      compound may be in part unrelated to its hemodynamic activity.

PMID- 10945846
TI  - Stereoselective interactions of the enantiomers of chromanol 293B with human
      voltage-gated potassium channels.
AB  - Selective inhibitors of the slow component of the cardiac delayed rectifier K(+)
      current, I(Ks), are of interest as novel class III antiarrhythmic agents and as
      tools for studying the physiologic roles of the I(Ks) current. Racemic chromanol
      293B is an inhibitor of both native I(Ks) and its putative molecular counterpart,
      the KvLQT1+minK ion channel complex. We synthesized the (+)-[3S,4R] and (-)
      [3R,4S] enantiomers of chromanol 293B using chiral intermediates of known
      absolute configuration and determined their relative potency to block recombinant
      human K(+) channels that form the basis for the major repolarizing K(+) currents
      in human heart, including KvLQT1+minK, human ether-a-go-go-related gene product
      (hERG), Kv1.5, and Kv4.3, corresponding to the slow (I(Ks)), rapid (I(Kr)), and
      ultrarapid (I(Kur)) delayed rectifier currents and the transient outward current
      (I(To)), respectively. K(+) channels were expressed in mammalian cells and
      currents were recorded using the whole-cell patch-clamp technique. We found that
      the physicochemical properties and relative potency of the enantiomers differed
      from those reported previously, with (-)-[3R,4S]293B nearly 7-fold more potent in
      block of KvLQT1+minK than (+)-[3S,4R]293B, indicating that the original
      stereochemical assignments were reversed. K(+) current inhibition by (-)-293B was
      selective for KvLQT1+minK over hERG, whereas the stereospecificity of block for
      KvLQT1+minK and Kv1.5 was preserved, with (-)-293B more potent than (+)-293B for
      both channel complexes. We conclude that the (-)-[3R,4S] enantiomer of chromanol
      293B is a selective inhibitor of KvLQT1+minK and therefore a useful tool for
      studying I(Ks).

PMID- 10945847
TI  - Influence of purinoceptor antagonism on diadenosine pentaphosphate-induced
      hypotension in anesthetized rats.
AB  - Diadenosine polyphosphates (ApnA; n = 3-6) are potent vasoactive agents in
      isolated vessels. Information on effects of ApnA in vivo is still limited despite
      the fact that these compounds are starting to be used in humans. This study was
      designed to compare the effects of ApnA and their possible metabolites on blood
      pressure in vivo and to functionally identify purinoceptors involved in their
      action. All four ApnA and their degradation products induced a sustained drop of
      mean arterial blood pressure during i.v. infusion, which was fully reversible.
      The rank order of potency was Ap4A > or = Ap6A > Ap5A = Ap3A = ATP = ADP > AMP >
      or = adenosine, suggesting that the hypotensive effect is predominantly evoked by
      the original dinucleotides and not by their degradation products. The hypotensive
      effect of Ap5A was reduced by the P2X and P2Y(1) purinoceptor antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, the A(1) purinoceptor
      antagonist 8-cyclopentyl-1,3-dipropylxanthine, and the A(2) purinoceptor
      antagonist 3, 7-dimethyl-1-propargylxanthine. The hypertensive effect by the
      prototype P2X receptor agonist alphabeta-methylene ATP was inhibited by pyridoxal
      phosphate-6-azophenyl-2',4'-disulfonic acid, too. Purinoceptor antagonists
      reduced the maximal effects of the agonists indicating a noncompetitive
      inhibition. In summary, the reported vasocontractile effect of ApnA seems to be
      limited to isolated preparations under resting tone conditions; however, the
      systemic cardiovascular effects of all four ApnA are hypotensive, also making
      them candidates for blood pressure reduction in humans. These effects are fast in
      onset and easily reversible. Activation of different purinoceptors in the
      vasculature (most probably P2Y(1) and A(2) receptors) contributes to the Ap5A
      induced decrease of mean arterial blood pressure.

PMID- 10945848
TI  - Alterations in G-proteins and beta-adrenergic responsive adenylyl cyclase in rat
      urinary bladder during aging.
AB  - Decreased response of bladder to beta-adrenergic stimulation with aging is
      related to decreased adenylyl cyclase activity and possibly to changes in guanine
      nucleotide regulatory protein (G-protein) content or function. G-protein content
      was quantified by Western blot analysis using antibodies to Gsalpha, Goalpha, and
      Gialpha in 21-day-old (weanling), 90-day-old (young adult), 6-month-old (adult),
      and 24-month-old (old) rat bladders. Gi/Go function in bladders with aging was
      measured by ADP-ribosylation with pertussis toxin. Content of Gsalpha, Goalpha,
      and Gialpha was lower in 90-day-old bladder than in 21-day-old bladder. Gsalpha
      content was similar in the 21-day-, 6-month-, and 24-month-old bladders. Gialpha
      content as well as pertussis toxin-catalyzed ADP-ribosylation was higher in 24
      month-old bladders than in 21- and 90-day-old bladders. Pertussis toxin-catalyzed
      ADP-ribosylation of bladder membranes and treatment of bladder with protein
      kinase A inhibitors reversed the age-dependent decline in isoproterenol
      stimulation of adenylyl cyclase. Decreases in beta-adrenergic-induced relaxation
      response with age in rat bladder are due in part to increases in the content and
      functional activity of pertussis toxin-sensitive G-protein.

PMID- 10945849
TI  - Antagonism of delta(2)-opioid receptors by naltrindole-5'-isothiocyanate
      attenuates heroin self-administration but not antinociception in rats.
AB  - delta-Opioid receptors have been implicated in reinforcement processes and
      antagonists are available that produce long-lasting and selective antagonism of
      delta-opioid receptors in vivo. This experiment assessed the contribution of
      delta-opioid receptors to the antinociceptive and reinforcing properties of
      heroin. The effects of the irreversible delta-antagonist naltrindole-5'
      isothiocyanate (5'-NTII) were evaluated on heroin self-administration and hot
      plate antinociception in rats. 5'-NTII (10 nmol i.c.v.) shifted the dose-response
      curve for heroin self-administration downward, increasing the A(50) values on the
      ascending and descending limbs by approximately 0.5 log units and decreasing the
      maximum by 33%. 5'-NTII (40 nmol i.c.v.) shifted both limbs of the heroin self
      administration dose-effect curve 1.2 log units to the right and decreased the
      maximum by 90%. Heroin self-administration gradually returned to baseline levels
      over 7 or 17 days after administration of 10 or 40 nmol 5'-NTII, respectively. 5'
      NTII (40 nmol i.c.v.) decreased the self-administration of 0.17 mg/infusion
      cocaine by 40% while having no effect on responding maintained by 0.33 or 0.67
      mg/infusion. 5'-NTII attenuated the antinociceptive effects of deltorphin
      (delta(2)) in a dose-dependent manner while having no effect on antinociception
      elicited after i.c. v. administration of [D-Pen(2),D-Pen(5)]-enkephalin
      (delta(1)) or [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (mu). In addition, the
      antinociceptive effects of heroin were not significantly affected by 5'-NTII (40
      nmol i.c.v.). Therefore, 5'-NTII can attenuate the reinforcing effects of heroin
      at doses that do not affect its antinociceptive effects. Long-acting delta(2)
      opioid antagonists may be beneficial in the treatment of heroin dependence or as
      adjuncts to reduce the abuse liability of opioid analgesics.

PMID- 10945850
TI  - Dose-dependent effects of recombinant human interleukin-11 on contractile
      properties in rabbit 2,4,6-trinitrobenzene sulfonic acid colitis.
AB  - We studied the effect of recombinant human interleukin-11 (rhIL-11), a cytokine
      with protective effects against injury to the intestinal mucosa, on inflammatory
      changes in the muscle layers of the gut, in rabbits with colitis. A single dose
      of rhIL-11 (4, 40, or 720 microg/kg) was given 1 h before colitis was induced
      with 135 mg/kg 2, 4,6-trinitrobenzene sulfonic acid (TNBS), followed by a
      continuous s. c. administration of 4, 40, or 720 microg/kg. day rhIL-11 or saline
      for 5 days. Colitis affected mucosal architecture, general mechanical properties
      (passive tension increased with 12.3 g/mm(2), optimal stretch decreased with
      26%), and collagen content (decreased from 366 +/- 25 to 237 +/- 13 microg/mg of
      protein). Changes in passive tension and collagen content were normalized by the
      highest and lowest dose of rhIL-11, respectively, but neither dose could
      normalize the optimal stretch. Colitis also decreased maximal contractile tension
      in response to acetylcholine (ACh), motilin, substance P (SP), K(+), and
      prostaglandin E(2) but this was normalized with 40 microg/kg. day (motilin, SP)
      and 720 microg/kg. day (ACh, K(+)) rhIL-11 but not for prostaglandin E(2). For
      motilin and SP, receptor density was decreased in colitis and normalized in
      treated rabbits. Colitis also increased the contractile potency toward ACh, an
      effect already reversed by rhIL-11, 4 microg/kg. day. In conclusion, rhIL-11
      partially normalizes disturbed tension generation in experimental colitis. The
      use of this cytokine in the treatment of irritable bowel disease may contribute
      to the restoration of motor dysfunction.

PMID- 10945851
TI  - Phorbol-stimulated Ca(2+) mobilization and contraction in dispersed intestinal
      smooth muscle cells.
AB  - This study examined the source of Ca(2+) mobilized by phorbol esters and its
      requirement for phorbol-induced contraction of smooth muscle cells isolated from
      the circular and longitudinal layers of guinea pig intestine. Phorbol-12
      myristate-13-acetate caused rapid, sustained, concentration-dependent muscle
      contraction and increase in cystolic free [Ca(2+)](i) in muscle cells from both
      layers. Maximal contraction was similar to that elicited by receptor-linked
      agonists, whereas maximal [Ca(2+)](i) was 50% less. The increase in [Ca(2+)](i)
      was mediated by Ca(2+) release in circular, and Ca(2+) influx in longitudinal
      muscle cells; only the latter was abolished by methoxyverapamil and in Ca(2+)
      free medium. [Ca(2+)](i) was essential for contraction in both cell types:
      contraction in longitudinal muscle cells was abolished by methoxyverapamil and in
      Ca(2+)-free medium; contraction in circular muscle cells was abolished only after
      depletion of Ca(2+) stores. Contraction was abolished by the protein kinase C
      (PKC) inhibitor calphostin C (1 microM), but was not affected by the myosin light
      chain kinase inhibitor KT5926 (1 microM), suggesting that activation of myosin
      light chain kinase was suppressed by phorbol-12-myristate-13-acetate or via PKC.
      Phorbol-induced contraction of permeabilized circular and longitudinal muscle
      cells was abolished by pretreatment with a common antibody to Ca(2+)-dependent
      PKC-alpha,beta,gamma, but was not affected by pretreatment with a specific PKC
      epsilon antibody. This study demonstrates the ability of phorbol esters to
      mobilize Ca(2+) from different sources in different smooth muscle cell types and
      establishes the requirement of Ca(2+) for phorbol-induced contraction; the latter
      is exclusively mediated by Ca(2+)-dependent PKC isozymes.

PMID- 10945852
TI  - Nitric oxide and its metabolites mediate ethanol-induced microtubule disruption
      and intestinal barrier dysfunction.
AB  - Loss of gastrointestinal (GI) barrier integrity has been implicated in a wide
      range of inflammatory illnesses, including alcoholic cirrhosis. Using monolayers
      of Caco-2 (intestinal) cells as a model, we showed that the ability of ethanol
      (EtOH) to disrupt intestinal barrier integrity depends on damage to the
      microtubule (MT) cytoskeleton, especially oxidative injury. One drug that
      prevented both the MT damage and barrier disruption was L-N(6)-1-iminoethyl
      lysine, a selective inhibitor of the inducible form of nitric-oxide synthase
      (iNOS). Because of this finding and because overproduction of nitric oxide (NO)
      and generation of peroxynitrite (ONOO(-)) have been proposed to be responsible
      for mucosal injury in other GI disorders, we sought to determine whether NO
      overproduction and ONOO(-) formation mediates EtOH-induced MT damage and loss of
      intestinal barrier function. To this end, Caco-2 monolayers were exposed to EtOH
      or to authentic ONOO(-) or ONOO(-) generators with or without pretreatment with
      iNOS inhibitors or antioxidants. We found that EtOH caused 1) iNOS activation, 2)
      NO overproduction, 3) increases in oxidative stress and superoxide anion
      production (superoxide dismutase quenchable fluorescence of dichlorofluorescein),
      4) nitration and oxidation of tubulin (immunoblotting), 5) decreased levels of
      stable polymerized tubulin, and 6) increased levels of disassembled tubulin. EtOH
      also 7) extensively damaged the MT cytoskeleton and 8) disrupted barrier
      function. Authentic ONOO(-) or ONOO(-) donors had similar effects. Pretreatment
      with a selective iNOS inhibitor, L-N(6)-1-iminoethyl-lysine, or with antioxidants
      (ONOO(-) scavengers urate or L-cysteine; superoxide anion scavenger superoxide
      dismutase) attenuated damage due to EtOH or to ONOO(-) generators. We conclude
      that EtOH-induced MT damage and intestinal barrier dysfunction require iNOS
      activation followed by NO overproduction and ONOO(-) formation. These findings
      provide a rationale for the development of novel therapeutic agents for alcohol
      induced GI disorders that inhibit this mechanism.

PMID- 10945853
TI  - Influence of heme oxygenase inhibitors on the basal tissue enzymatic activity and
      smooth muscle relaxation of internal anal sphincter.
AB  - We examined the actions of different heme oxygenase (HO) inhibitors on the basal
      HO activity in the opossum internal anal sphincter (IAS), rectum, and liver
      tissues and the IAS smooth muscle relaxation in response to nonadrenergic
      noncholinergic (NANC) nerve stimulation and different agonists. All the tissues
      examined were found to have significant levels of basal HO activity. Among
      different HO inhibitors, tin protoporphyrin IX (SnPP IX) was found to be most
      selective in inhibiting the HO activity in the IAS smooth muscle. Conversely, in
      the liver, all the HO inhibitors except SnPP IX caused significant inhibition of
      HO activity. Consistent with HO activity inhibition, the IAS smooth muscle
      relaxations caused by NANC nerve stimulation and vasoactive intestinal
      polypeptide also were inhibited by zinc protoporphyrin IX and SnPP IX. Zinc
      protoporphyrin IX also caused a significant attenuation of the IAS smooth muscle
      relaxation caused by isoproterenol. The IAS smooth muscle relaxation caused by
      nitric oxide was not significantly modified by any of the HO inhibitors. The data
      show the presence of HO activity in the IAS and other gastrointestinal tissues.
      The differential attenuation of HO activity by different HO inhibitors in the IAS
      smooth muscle and liver confirms the presence of different isozymes of HO in
      different tissues. Suppression of basal HO activity and the IAS smooth muscle
      relaxation induced by NANC nerve stimulation or VIP but not NO suggest that some
      of the stimuli that cause IAS smooth muscle relaxation may involve HO activity.

PMID- 10945854
TI  - Muscarinic cholinergic modulation of prepulse inhibition of the acoustic startle
      reflex.
AB  - The purpose of the present study was to determine the effects of muscarinic
      cholinergic receptor antagonists and agonists on prepulse inhibition (PPI) of the
      acoustic startle reflex in rats. The muscarinic receptor antagonist scopolamine
      (0.03-1.0 mg/kg) produced a significant dose-dependent decrease in PPI without
      affecting startle amplitude. In contrast, N-methyl scopolamine, the quaternary
      analog of scopolamine, had no effect on PPI, indicating that scopolamine
      disrupted PPI through a central cholinergic mechanism. Two other muscarinic
      receptor antagonists, trihexyphenidyl (0.3-10 mg/kg) and benztropine (0.03-10
      mg/kg), produced significant decreases in PPI similar to scopolamine. On the
      other hand, the muscarinic receptor antagonists dicyclomine (0.03-10 mg/kg) and
      biperiden (0.03-10 mg/kg) had no effect on PPI but significantly decreased
      startle amplitude. Mecamylamine (0.1-10 mg/kg), a nicotinic receptor antagonist,
      also had no effect on PPI. Administered alone, the muscarinic receptor agonists
      pilocarpine (0. 03-10 mg/kg), oxotremorine (0.01-0.3 mg/kg), RS-86 (0.1-3.0
      mg/kg), and arecoline (0.3-10 mg/kg), as well as the cholinesterase inhibitors
      physostigmine (0.01-0.3 mg/kg) and tacrine (0.03-10 mg/kg), had no effect on PPI,
      but each produced significant decreases in startle amplitude at the highest doses
      tested. In addition, the disruption of PPI by scopolamine was reversed in a dose
      dependent manner by the muscarinic receptor agonist oxotremorine. The present
      findings demonstrate that the muscarinic cholinergic system plays an important
      role in the normal mechanisms of PPI.

PMID- 10945855
TI  - Interaction of p-fluorofentanyl on cloned human opioid receptors and exploration
      of the role of Trp-318 and His-319 in mu-opioid receptor selectivity.
AB  - In this study, we investigated the interactions of p-fluorofentanyl, an opioid
      designer drug, fentanyl, sufentanyl, and morphine on cloned human mu-, kappa-,
      and delta-opioid receptors coexpressed with heteromultimeric G protein-coupled
      inwardly rectifying K(+) channels (GIRK1/GIRK2) and a regulator of G protein
      signaling (RGS4) in Xenopus oocytes. We demonstrate that p-fluorofentanyl more
      potently activates GIRK1/GIRK2 channels through opioid receptors than fentanyl
      and that the p-fluoro substitution also changes the potency profile from mu >
      kappa > delta (fentanyl) to mu > delta > or = kappa (p-fluorofentanyl). A
      comparison of ligand efficacy revealed that morphine, fentanyl, and its analogs
      less efficiently activate GIRK1/GIRK2 channels through human mu-opioid receptor
      than [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin. Using site-directed
      mutagenesis, we investigated whether mutating residues Trp-318 and His-319 to
      their corresponding residues in kappa- and delta-opioid receptors provides the
      molecular basis for mu/delta selectivity and mu/kappa selectivity. Changes in
      EC(50) values for the W318L and W318Y/H319Y mu-opioid receptors show a partial
      contribution of these residues to the decreased GIRK1/GIRK2 channel activation by
      fentanyl analogs through kappa- and delta-opioid receptors. The most pronounced
      effect was observed for p-fluorofentanyl, suggesting that an interaction between
      the 4-fluorophenylpropanamide moiety of the drug and residues Trp-318 and His-319
      is important for the resulting enhanced GIRK1/GIRK2 channel activation through
      the mu-opioid receptor. Finally, we demonstrate that mutation of W318L confers
      delta-like potency for morphine on the mutant mu-opioid receptor.

PMID- 10945856
TI  - Adenosine and selective A(2A) receptor agonists reduce ischemia/reperfusion
      injury of rat liver mainly by inhibiting leukocyte activation.
AB  - To examine whether adenosine reduces ischemia/reperfusion (I/R)-induced liver
      injury by inhibiting leukocyte activation via A(2) receptor (A(2)R) stimulation,
      we investigated the effects of adenosine and selective A(2A) receptor (A(2A)R)
      agonists (YT-146 and CGS21680C) on I/R-induced liver injury in rats. Adenosine,
      YT-146, and CGS21680C, in the concentration of 10(-7) to 10(-5) M, significantly
      inhibited neutrophil elastase release by about 30 to 40% and increased
      intracellular Ca(2+) concentrations in isolated neutrophils stimulated with
      formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro. Adenosine, YT-146, and
      CGS21680C, in the concentration of 10(-7) to 10(-5) M, significantly inhibited
      tumor necrosis factor (TNF)-alpha production by monocytes stimulated with
      endotoxin by about 50%. Although ZM241385, a selective A(2A)R antagonist,
      significantly enhanced the increase in neutrophil elastase release and
      intracellular Ca(2+) concentrations in neutrophils stimulated with fMLP, this
      agent did not affect the endotoxin-induced TNF-alpha production by monocytes.
      Rats were subjected to liver ischemia for 60 min. Serum levels of transaminases
      increased after hepatic I/R, peaking at 12 h after reperfusion. The i.v. infusion
      of adenosine (1 and 10 mg/kg/h), YT-146 (0.1 and 1 mg/kg/h), and CGS21680C (0.1
      and 1 mg/kg/h) significantly inhibited the I/R-induced increase in serum
      transaminase levels 12 h after reperfusion. The I/R-induced decrease in hepatic
      tissue blood flow was significantly prevented by adenosine and YT-146. Hepatic
      levels of TNF-alpha, cytokine-induced neutrophil chemoattractant (equivalent to
      human interleukin-8), and myeloperoxidase were significantly increased after I/R.
      These increases were significantly inhibited by the administration of adenosine,
      YT-146, and CGS21680C. Although the histological neutrophil accumulation in the
      liver was significantly increased after I/R as evaluated by the naphthol AS-D
      chloroacetate technique, the administration of adenosine, YT-146, and CGS21680C
      significantly inhibited this increase. These findings suggest that adenosine
      reduces I/R-induced liver injury both by inhibiting the synthesis of inflammatory
      mediators and by inhibiting neutrophil degranulation directly, probably through
      A(2A)R stimulation.

PMID- 10945857
TI  - Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis.
AB  - Development of severe sepsis is thought to result from the overproduction of
      cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta
      (IL-1beta), and nitric oxide. Recently, 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors, which are antihypercholesterolemic agents, have been
      reported to inhibit lipopolysaccharide (LPS)-induced production of cytokines and
      nitric oxide in vitro. In this study, we tested these effects in vivo. After LPS
      administration (15 mg/kg i.p.) to CD-1 mice, serum levels of both TNF-alpha and
      IL-1beta transiently increased, and peaked at 2 h. After the peak responses of
      TNF-alpha and IL-1beta, serum levels of nitrite and nitrate increased until at
      least 8 h. Pretreatment of the mice with cerivastatin (20 mg/kg i.p. 12 and 1 h
      before LPS injection) reduced serum levels of TNF-alpha and IL-1beta at 2 h, and
      nitrite and nitrate at 8 h, by 93, 60, and 44%, respectively. In this model of
      sepsis, cerivastatin significantly (P =.016) improved the rate of 7-day survival
      from 26.7 to 73.3%. These results cast new light on the usefulness of
      cerivastatin in preventing severe sepsis.

PMID- 10945858
TI  - Endothelin(A) receptor subtype mediates endothelin-induced contractility in left
      ventricular cardiomyocytes isolated from rabbit myocardium.
AB  - Endothelin (ET)-1 is a potent positive inotropic agent, the effects of which are
      mediated by increases in cytosolic Ca(2+) in the myocardium. The object of this
      study was to examine 1) the influence of ET(A) and ET(B) receptor subtypes, and
      2) the role of the phospholipase C (PLC) pathway in mediating ET-1-induced
      contraction. Left ventricular cardiomyocytes were isolated from the hearts of New
      Zealand White rabbits (2-2.5 kg) by the use of Langendorff perfusion with
      collagenase. Cardiomyocyte function was examined during unloaded, electrically
      stimulated (0.5 Hz) contractions with a video-edge detection system. ET-1
      increased cell shortening with greater potency than ET-3: mean EC(50) values were
      1.1 x 10(-11) and 2.6 x 10(-10) M, respectively. With the same order of potency,
      ET-1 and ET-3 increased (P <.05) velocity of cell shortening. The ET(A) receptor
      selective antagonist ABT-627 shifted the ET-1-induced cell shortening response
      curve to the right with a pA(2) value of 10.3. The ET(B) receptor-selective
      antagonist A-192621 (10(-8)-10(-7) M) did not alter the concentration-response of
      ET-1. Moreover, the ET(B) receptor-selective agonist sarafotoxin 6c did not have
      any effect on cell shortening over the concentration range of 10(-11) to 10(-7)
      M. ET-1 in the presence of the PLC inhibitor U-73122 did not alter the
      contractile amplitude. However, ET-1 in the presence of the protein kinase C
      inhibitor bisindolylmalemide increased cell shortening. These findings indicate
      that 1) the ET(A) receptor subtype, and not the ET(B) receptor subtype, mediates
      the positive inotropic effect of ET-1, and 2) the response of ET-1 is mediated by
      a PLC pathway, but not through protein kinase C, in ventricular cardiomyocytes
      isolated from rabbit myocardium.

PMID- 10945859
TI  - Two amino acids in the sixth transmembrane segment of the mouse gastrin-releasing
      peptide receptor are important for receptor activation.
AB  - The gastrin-releasing peptide receptor (GRP-R) is a G protein-coupled receptor
      that mediates a variety of cellular responses, including cell growth and
      modulation of neuronal activity by activation of heterotrimeric GTP-binding
      proteins in the Gq family. To understand the regulation of GRP-R signaling we
      have substituted alanine for each of 10 amino acid residues within the
      transmembrane (TM) helices of the GRP-R predicted to project into the binding
      pocket of the receptor and analyzed the importance of each of these residues for
      receptor function. Two mutations showed selective loss of either agonist (Y285A)
      or antagonist (F313A) affinity for the GRP-R. In addition, we identified two
      amino acid residues, Phe(270) and Asn(281), in the sixth TM segment, which are
      important for receptor-G protein interaction. In a competition-binding assay with
      an antagonist radioligand, bombesin showed a 20- to 100-fold decreased affinity
      for the N281A and F270A mutant GRP-R compared with wild-type GRP-R. The
      saturation-binding isotherms are best fit by a two-state model, indicating that
      the receptors are in either a low-affinity (K(D2)) or a high-affinity (K(D1))
      state. The ratio of the two affinities (K(D2)/K(D1)) was significantly increased
      for both mutants compared with wild-type GRP-R, whereas the fraction of mutant
      receptors in the high-affinity state (R(1)) was decreased. GDP/guanosine-5'-O-(3
      thio)triphosphate exchange catalyzed by the N281A mutant was lower than that
      observed for the wild-type GRP-R. However, for both mutants, bombesin was still
      able to stimulate 1,4,5-inositol triphosphate in transfected cells albeit with
      reduced activity. We conclude that these two TM residues are important for
      receptor-G protein coupling, and postulate that each mutation may affect GRP-R
      conformational change to the high-affinity, G protein-coupled state.

PMID- 10945860
TI  - Vesicular transport of newly synthesized cytochromes P4501A to the outside of rat
      hepatocyte plasma membranes.
AB  - Anti-cytochrome P450 (CYP)1A2 autoantibodies are found in dihydralazine-induced
      hepatitis, and CYPs2B and 2C have been shown to follow vesicular flow to the
      plasma membrane (PM). However, it is unknown whether other CYPs follow this
      route, whether NADPH-CYP reductase is present on the hepatocyte surface, and
      whether autoimmune hepatitis-inducing drugs increase PM CYPs. In this study, we
      determined the transmembrane topology and transport of CYPs1A in rat hepatocytes.
      In cultured hepatocytes, colchicine and other vesicular transport inhibitors
      decreased PM CYPs1A assessed by flow cytometry. Colchicine administration also
      decreased PM CYPs1A in vivo. Pulse chase experiments with [(35)S]methionine
      showed that only the newly synthesized CYP molecules are transferred to the PM,
      whereas microsomal CYP1A2 was stably radiolabeled for several hours. In contrast,
      radiolabeled CYP1A2 reached the PM and disappeared from the PM with half-lives of
      less than 30 min. Confocal microscopy, biotinylation, and coimmunoprecipitation
      experiments showed that PM CYPs1A and CYP reductase are present on the cell
      surface, and that the reductase is closely associated with PM CYPs. Exposure of
      whole cells to an anti-CYP1A1/2 antibody at 4 degrees C, before five washes and
      PM preparation, abolished PM CYPs1A-supported monooxygenase activity, indicating
      that PM CYPs are mostly located on the external surface. Dihydralazine and other
      CYPs1A inducers increased PM CYPs1A. In conclusion, newly synthesized CYPs1A
      follow vesicular flow to the outside of the PM, and NADPH-CYP reductase also is
      located on the hepatocyte surface. Dihydralazine administration increases PM
      CYP1A2, its autoimmune target.

PMID- 10945861
TI  - Antitumor imidazolyl disulfide IV-2 causes irreversible G(2)/M cell cycle arrest
      without hyperphosphorylation of cyclin-dependent kinase Cdk1.
AB  - Aberrant function of redox-regulated proteins is a possible cause for cellular
      transformation and loss of cell cycle control. The small protein thioredoxin has
      oncogenic properties and controls cell cycle movement through G(1), S, and G(2)/M
      phases. The redox-active, asymmetrical 1-methylpropyl-2-imidazolyl disulfide (IV
      2) has previously been shown to react with and inhibit thioredoxin activity in
      vitro, the proliferation of human tumor cells in culture, and the growth of
      tumors in mice. We now examined the effects of IV-2 on cell cycle progression. In
      synchronized tsFT210 mouse mammary carcinoma cells, IV-2 halted cells in mitosis.
      In asynchronously growing MCF-7 human breast cancer cells, IV-2 exclusively and
      irreversibly blocked cells in G(2)/M at concentrations that correlated with its
      growth inhibitory activity. Neither the closely related, less redox active 2
      hydroxy-1-methylpropyl-2-imidazolyl disulfide (AIV-2), which differs from IV-2
      only by an additional hydroxyl group, nor the symmetrical diallyl disulfide
      caused a G(2)/M arrest under these conditions. Furthermore, MCF-7 cells treated
      with IV-2 showed increased Cdk1 kinase activity and a decrease in Cdk1 tyrosine
      phosphorylation, indicating that IV-2 did not directly inhibit Cdk1 or Cdc25
      activities. IV-2 did, however, increase Bcl-2 phosphorylation. These data suggest
      that the thioredoxin inhibitor IV-2, despite its simple structure, is able to
      target redox-sensitive processes that are critical for cell cycle progression
      through mitosis. The results are also consistent with a role of thioredoxin
      regulating cell cycle progression through G(2)/M.

PMID- 10945862
TI  - Synergistic stimulation of airway smooth muscle cell mitogenesis.
AB  - Previous studies showed that human airway smooth muscle (HASM) cells treated with
      lysophosphatidic acid (LPA), a pertussis toxin (PTX)-sensitive G protein-coupled
      (GPC) mitogen, simultaneously with epidermal growth factor (EGF), a receptor
      tyrosine kinase (RTK) mitogen, exhibit markedly synergistic stimulation of
      mitogenesis. We now show that the RTK mitogens basic fibroblast growth factor,
      insulin-like growth factor-1, insulin, platelet-derived growth factor-AA, and
      platelet-derived growth factor-BB, as well as transforming growth factor-beta,
      all induced synergistic stimulation of mitogenesis in the presence of LPA. The
      PTX-sensitive GPC mitogens carbachol and endothelin-1 and the PTX-insensitive GPC
      mitogens sphingosine-1-phosphate and thrombin exhibited synergistic stimulation
      together with EGF. Several RTK-RTK growth factor pairs and GPC-GPC mitogen pairs
      were also synergistic. HASM cells showed synergistic responses to serum plus EGF
      but not to serum plus LPA. Testing various other cell types showed that synergism
      between LPA and EGF occurred in other smooth muscle cells because both vascular
      smooth muscle cells and mesangial cells exhibited synergism. Additionally, human
      fetal lung fibroblasts also showed striking synergism. These results indicate
      that HASM cells can respond synergistically to a wide variety of mitogen
      combinations and that this synergism is a feature shared with other contractile
      cell types.

PMID- 10945863
TI  - Efficacy of novel calpain inhibitors in preventing renal cell death.
AB  - Inhibitors of calpains, calcium-activated neutral proteases, protect against cell
      death produced by anoxia and a variety of toxicants both in vitro and in vivo.
      The problems with known calpain inhibitors are a lack of specificity, low
      membrane permeability, and/or low potency. The goal of this study was to
      determine the effects of seven novel dipeptide and tripeptide calpain inhibitors
      on calpain activity and antimycin A-induced cell death in rabbit renal proximal
      tubule (RPT) suspensions. We chose the compounds based on their inhibitory
      constants for mu- versus m-calpain, specificity of the inhibitors for calpain,
      and membrane permeability. Only three of the compounds inhibited calpain in RPT
      and were cytoprotective (Z-Leu-Phe-COOH, Z-Leu-Abu-CONH-CH(2)-CH(OH)-Ph, and Z
      Leu-Phe-CONH-Et). Interestingly, Z-Leu-Phe-COOEt, Z-Leu-Abu-CONH-CH(2)-CH(OH)
      C(6)F(5), and Z-Leu-Abu-CONH-CH(2)-2-quinolinyl were greater than 60%
      cytoprotective but did not inhibit calpain in RPT. Z-Leu-Abu-CONH(CH(2))(3)
      morpholine was neither cytoprotective nor inhibited calpain. Although these
      results suggest that six of the seven peptide calpain inhibitors are cell
      permeable, only three of them inhibited calpain activity in RPT and were
      cytoprotective. Their ability to inhibit calpain or produce cytoprotection did
      not correlate with their ability to selectively inhibit purified mu- or m
      calpain. Thus it remains to be determined whether they inhibit mu-calpain, m
      calpain, or both in RPT. These results also suggest that inhibition of other
      protease(s) in addition to calpains may be responsible for the cytoprotective
      actions of some compounds.

PMID- 10945864
TI  - Uptake of imipramine in rat liver lysosomes in vitro and its inhibition by basic
      drugs.
AB  - We investigated the uptake of imipramine (IMP) in highly purified lysosomes from
      rat liver and its inhibition by a variety of basic drugs in vitro. The uptake of
      [(3)H]IMP into lysosomes peaked in less than 20 s, showing little temperature
      dependency or countertransport phenomena. It was accelerated by increase of
      extralysosomal pH, stimulated by Mg(2+)-ATP in KCl buffer, and suppressed by
      acidic ionophores. However, the uptake of [(3)H]IMP in lysosomes was
      approximately 140-fold higher than the value expected from the pH-partition
      theory. IMP and other weak lipophilic bases like chlorpromazine and propranolol
      raised the intralysosomal pH, and their potency was stronger than that of
      NH(4)Cl, a typical pH-perturbing weak base. A variety of basic drugs inhibited
      the uptakes of [(3)H]IMP and [(14)C]methylamine into lysosomes, their 50%
      inhibitory concentrations (IC(50)) being almost the same for [(3)H]IMP and
      [(14)C]methylamine uptake (r = 0.842). A high correlation (r = 0.946) was
      observed between the IC(50) values (for the inhibition of [(3)H]IMP uptake) and
      the lipophilicity (P(oct) values). These results suggest that the accumulation of
      lipophilic basic drugs is driven primarily by the transmembrane pH difference (pH
      partition theory) but with the involvement of some additional mechanism(s)
      related to drug lipophilicity, possibly binding (partition or adsorption) to
      lipophilic substance(s) and/or aggregation within lysosomes. Based on this idea,
      we have established a model that described and successfully simulated the weak
      base-induced pH increase, the accumulation of a lipophilic weak base (IMP), and
      the inhibition of accumulation of IMP by lipophilic basic drugs.

PMID- 10945865
TI  - CYP1A2 and CYP2D6 4-hydroxylate propranolol and both reactions exhibit racial
      differences.
AB  - We have previously shown racial differences in propranolol kinetics, with the
      largest differences appearing to be in its 4-hydroxylation. The purpose of this
      study was to identify and confirm the cytochrome P450 enzymes (CYP) with
      propranolol 4-hydroxylase activity, describe their enzyme kinetics, and determine
      whether there were racial differences in their catalytic activity. Eleven human
      recombinant, expressed CYPs were screened, but only CYP1A2 and CYP2D6 possessed
      propranolol 4-hydroxylase activity. Subsequent studies were conducted in human
      liver microsomes, including correlation, inhibition, enzyme kinetics, and racial
      comparison studies. Significant correlations were noted between propranolol 4
      hydroxylation and ethoxyresorufin-O-deethylation (marker of CYP1A2 activity),
      with marked improvement in the correlations when CYP2D6-mediated propranolol 4
      hydroxylation was inhibited with quinidine. Inhibition studies showed that
      quinidine inhibited approximately 55% of propranolol 4-hydroxylation and
      furaphylline (CYP1A2-selective inhibitor) inhibited about 45% of propranolol 4
      hydroxylation. Median (range) parameter estimates of (S)-4-hydroxypropranolol
      [(S)-HOP] formation were a V(max) value of 307 (165-2397) and 721 (84-1975)
      pmol/mg of protein/60 min for CYP1A2 and CYP2D6, respectively, and a K(m) value
      of 21.2 (8.9-77.5) and 8.5 (5.9-31.9) microM for CYP1A2 and CYP2D6, respectively.
      CYP1A2- and CYP2D6-mediated propranolol 4-hydroxylation was about 70 and 100%
      higher (P <.05 for both), respectively, in African-Americans compared with
      Caucasians. In summary, we found that both CYP1A2 and CYP2D6 catalyze formation
      of 4-hydroxypropranolol and that both enzymes exhibited racial differences in
      this reaction. The observed racial differences in drug metabolism may have
      relevance to drug efficacy, toxicity, or carcinogen activation for CYP1A2 or
      CYP2D6 substrates.

PMID- 10945866
TI  - Differential mechanisms mediating descending pain controls for antinociception
      induced by supraspinally administered endomorphin-1 and endomorphin-2 in the
      mouse.
AB  - We have previously demonstrated that both endomorphin-1 and endomorphin-2 produce
      their antinociception by the stimulation of mu-opioid receptors. However, the
      antinociception induced by endomorphin-2 contains an additional component, which
      is mediated by the release of dynorphin A (1-17) acting on kappa-opioid
      receptors. These studies were done to determine whether the antinociception
      induced by endomorphin-1 and endomorphin-2 given supraspinally was mediated by
      the activation of different descending pain control pathways in the mouse.
      Specific receptor antagonists or antisera against endogenous opioid peptides were
      injected intrathecally to block the receptors or bind the released endogenous
      opioid peptides, and endomorphin-1 or endomorphin-2 was then administered i.c.v.
      to activate the descending pain control systems to produce antinociception. The
      tail-flick response was used as antinociceptive test. The blockade of the
      alpha(2)-adrenoceptors and 5-hydroxytryptamine receptors in the spinal cord by
      i.t. injection of yohimbine and methysergide, respectively, inhibited the
      antinociception induced by i.c.v.-administered endomorphin-1 and endomorphin-2.
      However, the antinociception induced by endomorphin-2 was inhibited by i.t.
      pretreatment with delta(2)-opioid receptor antagonist naltriben or kappa-opioid
      receptor antagonist nor-binaltorphimine, but not by the mu-opioid receptor
      antagonist D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH(2) or the delta(1)-opioid
      receptor antagonist 7-benzylidene naltrexamine. Intrathecal pretreatment with
      antiserum against Met-enkephalin attenuated the antinociception induced by i.c.v.
      administered endomorphin-2, but not endomorphin-1. Furthermore, i.t. pretreatment
      with antiserum against dynorphin A (1-17) also inhibited the antinociception
      induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Intrathecal
      pretreatment with antiserum against Leu-enkephalin or beta-endorphin did not
      inhibit i.c.v.-administered endomorphin-1- or endomorphin-2-induced
      antinociception. The results indicate that, like other opioid micro-receptor
      agonists, morphine, and [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin,
      endomorphin-1 and endomorphin-2 given i.c.v. produce antinociception by
      activating spinipetal noradrenergic and serotonergic pathways for producing
      antinociception. However, the antinociception induced by endomorphin-2 given
      i.c.v. also contains other components, which are mediated by the release of Met
      enkephalin and dynorphin A (1-17) acting on opioid delta(2)- and kappa-receptors,
      respectively, in the spinal cord.

PMID- 10945867
TI  - Evidence that nicotinic alpha(7) receptors are not involved in the hyperlocomotor
      and rewarding effects of nicotine.
AB  - Neuronal nicotinic receptors are comprised of combinations of alpha(2-9) and
      beta(2-4) subunits arranged to form a pentameric receptor. Currently, the
      principal central nervous system (CNS) subtypes are believed to be
      alpha(4)beta(2) and a homomeric alpha(7) receptor, although other combinations
      almost certainly exist. The identity of the nicotinic receptor subtype(s)
      involved in the rewarding effects of nicotine are unknown. In the present study,
      using some recently described subtype selective nicotinic agonists and
      antagonists, we investigated the role of the alpha(7) nicotinic receptor in the
      mediation of nicotine-induced hyperactivity and self-administration in rats. The
      alpha(7) receptor agonists AR-R 17779 and DMAC failed to stimulate locomotor
      activity in both nicotine-nontolerant and -sensitized rats. In contrast, nicotine
      and the putative alpha(4)beta(2) subtype selective agonist SIB1765F increased
      activity in both experimental conditions. In nicotine-sensitized rats, the high
      affinity (including the alpha(4)beta(2) subtype) nicotinic antagonist dihydro
      beta-erythroidine (DHbetaE), but not the selective alpha(7) antagonist
      methyllycaconitine (MLA), antagonized a nicotine-induced hyperactivity.
      Similarly, DHbetaE, but not MLA, pretreatment reduced nicotine self
      administration. Electrophysiology experiments using Xenopus oocytes expressing
      the human alpha(7) receptor confirmed AR-R 17779 and DMAC to be potent agonists
      at this site, and further studies demonstrated the ability of systemically
      administered AR-R 17779 to penetrate into the CNS. Taken together, these results
      indicate a negligible role of alpha(7) receptors in nicotine-induced
      hyperlocomotion and reward in the rat, and support the view for an involvement of
      a member from the high-affinity nicotinic receptor subclass, possibly
      alpha(4)beta(2). Issues such as drug potency, CNS penetration, and
      desensitization of the alpha(7) receptor are discussed.

PMID- 10945869
TI  - The importance of the hypothalamo-hypophyseal-adrenal axis to the anti
      inflammatory actions of the kappa-opioid agonist PNU-50,488H in rats with
      adjuvant arthritis.
AB  - Possible contributions of the hypothalamo-hypophyseal-adrenal axis to the
      development of adjuvant-induced arthritis and therapeutic actions of the
      prototypical kappa-opioid agonist PNU-50,488H (PNU-50) were studied in DA rats.
      Paw edema, nociception, histological and radiological joint damage, and tumor
      necrosis factor-alpha release by peritoneal macrophages were measured in
      adrenalectomized (ADX) and sham-operated (SHO) arthritic animals (drug-treated
      and untreated groups). Disease developed earlier in ADX rats (paw edema was first
      apparent 11 days postadjuvant compared with day 13 in SHO animals) and remained
      more severe in that group. Twice-daily PNU-50 treatment completely prevented the
      development of edema in the SHO group but was effective in the ADX animals only
      on day 18. PNU-50 substantially reduced the pooled severity index (combined
      quantitative edema, histological and radiological assessments) at day 18 in both
      SHO and ADX rats and to an equal extent. During disease development, the paws of
      SHO, but not ADX, rats became hyperalgesic; paradoxically, ADX animals were
      hyperalgesic during PNU-50 treatment, but the drug produced analgesia in SHO
      animals. Compared with cells harvested from healthy animals, macrophages from
      arthritic rats released about twice as much tumor necrosis factor-alpha after
      lipopolysaccharide stimulation. It was concluded that the hypothalamo-hypophyseal
      adrenal axis influences the development of adjuvant arthritis and plays a partial
      role in the therapeutic action of the kappa-agonist PNU-50.

PMID- 10945868
TI  - Recombinant cytochrome P450 2D18 metabolism of dopamine and arachidonic acid.
AB  - The function of cytochrome P450 (P450) in the mammalian brain is not well
      understood. In an effort to further this understanding, this study identifies two
      endogenous substrates for P450 2D18. Previous reports have shown that this
      isoform is expressed in the rat brain, and the recombinant enzyme catalyzes the N
      demethylation of the antidepressants imipramine and desipramine. By further
      examining the substrate profile of P450 2D18, inferences can be made as to
      potential endogenous P450 substrates. Herein we demonstrate the metabolism of the
      central nervous system-acting compounds chlorpromazine and chlorzoxazone with
      turnover numbers of 1.8 and 0. 9 nmol/min/nmol, respectively. Because the four
      aforementioned pharmaceutical substrates work by binding to neurotransmitter
      receptors, binding assays and oxidation reactions were performed to test whether
      dopamine is a substrate for P450 2D18. These data indicate a K(S) value of 678
      microM and that P450 2D18 can support the oxidation of dopamine to aminochrome
      through a peroxide-shunt mechanism. We also report the P450 2D18-mediated omega
      hydroxylation and epoxygenation of arachidonic acid, primarily leading to the
      formation of 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids, compounds that
      have been shown to have vasoactive properties in brain, kidney, and heart
      tissues. The data presented herein suggest a possible role for P450 involvement
      in membrane and receptor regulation via epoxyeicosatrienoic acid formation and a
      potential involvement of P450 in the oxidation of dopamine to reactive oxygen
      species under aberrant physiological conditions where the sequestering of
      dopamine becomes compromised, such as in Parkinson's disease.

PMID- 10945870
TI  - The effects of cocaine on basal and human chorionic gonadotropin-stimulated
      ovarian steroid hormones in female rhesus monkeys.
AB  - Cocaine stimulates gonadotropin (luteinizing hormone) release from the anterior
      pituitary in humans and in rhesus monkeys, but its acute effects on ovarian
      steroid hormones are unknown. The acute effects of cocaine and placebo on
      estradiol and progesterone were studied in 13 drug-naive female rhesus monkeys
      during the mid-follicular (days 8-10) and the mid-luteal (days 21-23) phases of
      the menstrual cycle. Each monkey was her own control under cocaine and placebo
      conditions. Samples for ovarian steroid hormone analysis were collected before
      and at 15-min intervals for 300 min after cocaine or placebo administration. In
      follicular phase females, estradiol levels increased significantly within 15 min
      after cocaine (0.8 mg/kg i.v.) administration (P <.008) but did not change after
      placebo administration. Estradiol remained significantly above baseline for 45
      min (P <.002-0.02). In contrast, in mid-luteal phase females, estradiol did not
      change after cocaine or placebo administration. Basal progesterone levels did not
      change after cocaine or placebo administration in either mid-follicular or mid
      luteal phase females. After hCG (500 I.U. i.m.) was administered to mid-luteal
      phase females, cocaine (0.4 and 0.8 mg/kg i.v.) and placebo administration did
      not increase or decrease estradiol or progesterone. One implication of these
      findings is that cocaine-induced increases in follicular phase estradiol levels
      could disrupt folliculogenesis and contribute to the menstrual cycle
      abnormalities observed during chronic cocaine self-administration.

PMID- 10945871
TI  - Potential clinical use of butyric acid derivatives to induce antigen-specific T
      cell inactivation.
AB  - Compounds with the capacity to induce antigen-specific unresponsiveness in CD4(+)
      T cells can in some clinical situations be more beneficial than general immune
      suppressants. Newly synthesized ester, ester/amide, and amide derivatives of
      butyrate with the capacity to induce antigen-specific T cell unresponsiveness in
      vivo and in vitro were tested here. The ester and ester/amide derivatives of
      butyrate were shown to block proliferation by interleukin-2-stimulated murine Th1
      cells in vitro. A 3-day treatment with these same two derivatives also suppressed
      a primary antibody response to a thymus-dependent antigen in mice. In addition,
      even a single injection of the ester derivative of n-butyrate 2-(4
      morpholinyl)ethyl butyrate hydrochloride (MEB) on day 2 or 3 after immunization
      suppressed the generation of memory T cells capable of proliferating to antigen
      or of promoting a secondary antigen-specific antibody response. MEB also induced
      antigen-specific unresponsiveness in antigen-activated, but not resting or
      interleukin-2-activated, T cells in vitro. DNA analysis showed that regardless of
      when MEB was added to the cultures, it induced the eventual G(1) sequestration of
      essentially all activated Th1 cells. Because G(1) blockade is associated with Th1
      cell anergy, this finding suggests that MEB has the potential to induce anergy in
      already-activated CD4(+) T cells. Taken together, the results presented here
      establish MEB as a novel means of inducing anergy in CD4(+) T cells both in vitro
      and in vivo and underscore the likelihood that MEB and/or other butyrate
      derivatives can be used as immunotherapeutic reagents.

PMID- 10945872
TI  - Pharmacological actions of a novel, high-affinity, and selective human dopamine
      D(3) receptor antagonist, SB-277011-A.
AB  - SB-277011-A (trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2
      yl)ethyl]cyclohexyl]-4-quinolininecarboxamide), is a brain-penetrant, high
      affinity, and selective dopamine D(3) receptor antagonist. Radioligand-binding
      experiments in Chinese hamster ovary (CHO) cells transfected with human dopamine
      D(3) or D(2 long) (hD(3), hD(2)) receptors showed SB-277011-A to have high
      affinity for the hD(3) receptor (pK(i) = 7.95) with 100-fold selectivity over the
      hD(2) receptor and over 66 other receptors, enzymes, and ion channels. Similar
      radioligand-binding data for SB-277011-A were obtained from CHO cells transfected
      with rat dopamine D(3) or D(2). In the microphysiometer functional assay, SB
      277011-A antagonized quinpirole-induced increases in acidification in CHO cells
      overexpressing the hD(3) receptor (pK(b) = 8.3) and was 80-fold selective over
      hD(2) receptors. Central nervous system penetration studies showed that SB-277011
      A readily entered the brain. In in vivo microdialysis studies, SB-277011-A (2. 8
      mg/kg p.o.) reversed the quinelorane-induced reduction of dopamine efflux in the
      nucleus accumbens but not striatum, a regional selectivity consistent with the
      distribution of the dopamine D(3) receptor in rat brain. SB-277011-A (2-42.3
      mg/kg p.o.) did not affect spontaneous locomotion, or stimulant-induced
      hyperlocomotion. SB-277011-A (4.1-42.2 mg/kg p.o.) did not reverse prepulse
      inhibition deficits in apomorphine- or quinpirole-treated rats, but did
      significantly reverse the prepulse inhibition deficit in isolation-reared rats at
      a dose of 3 mg/kg p.o. SB-277011-A (2.5-78. 8 mg/kg p.o.) was noncataleptogenic
      and did not raise plasma prolactin levels. Thus, dopamine D(3) receptor blockade
      produces few of the behavioral effects characteristic of nonselective dopamine
      receptor antagonists. The effect of SB-277011-A on isolation-induced prepulse
      inhibition deficit suggests that blockade of dopamine D(3) receptors may benefit
      the treatment of schizophrenia.

PMID- 10945873
TI  - Acute and chronic administration of the selective D(3) receptor antagonist SB
      277011-A alters activity of midbrain dopamine neurons in rats: an in vivo
      electrophysiological study.
AB  - This study examined the effect of acute and repeated p.o. administration of the
      selective D(3) receptor antagonist SmithKline Beecham (SB)-277011-A (1, 3, or 10
      mg/kg) on the activity of spontaneously active midbrain dopamine (DA) neurons in
      anesthetized, male Sprague-Dawley rats. This was accomplished with the technique
      of in vivo extracellular single-unit recording. A single administration of either
      3 or 10 mg/kg SB-277011-A produced a significant increase in the number of
      spontaneously active substantia nigra pars compacta (or A9) DA neurons compared
      with vehicle-treated (2% methylcellulose) animals. The 10-mg/kg dose of SB-277011
      A produced a significant increase in the number of spontaneously active A10 DA
      neurons compared with vehicle-treated animals. The acute administration of SB
      277011-A produced a significantly greater alteration in the firing pattern of
      spontaneously active A10 DA neurons, particularly at the 3- and 10-mg/kg doses,
      compared with vehicle-treated animals. The i.v. administration of SB-277011-A
      (0.01-1.28 mg/kg) did not significantly alter the firing rate or firing pattern
      of either A9 or A10 DA neurons. The repeated p.o. administration of 1, 3, or 10
      mg/kg SB-277011-A once a day for 21 days produced a significant decrease in the
      number of spontaneously active A10 DA neurons. The repeated administration of SB
      277011-A produced a greater effect on the firing pattern of spontaneously active
      A10 DA neurons, particularly at the 3-mg/kg dose, compared with A9 DA neurons.
      Overall, our results indicate that SB-277011-A alters the activity of midbrain DA
      neurons in rats.

PMID- 10945874
TI  - Diadenosine polyphosphates cause contraction and relaxation in isolated rat
      resistance arteries.
AB  - The effects of diadenosine polyphosphates (APnA; n = 3-6) and adenine nucleotides
      on contractile reactivity of isolated rat mesenteric resistance arteries (MrA)
      and superior epigastric arteries (SEA), which display a dense and sparse
      autonomic innervation, respectively, were evaluated. All agonists examined,
      except adenosine and AMP, induced contractions. The rank order of potency was
      similar in both arteries: alpha,beta-methylene ATP (alpha,beta-meATP) > AP5A >
      AP6A > AP4A > ATP > ADP > AP3A. Contractions were stable during several minutes
      in SEA but highly transient in MrA. They were reduced after exposure to 10 microM
      alpha,beta-meATP and by 10 microM of the P2X antagonist pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonic acid. During phenylephrine (10 microM)-induced
      contractions, the agonists induced a further contraction in SEA. In MrA, however,
      further contraction was followed by marked relaxation. The rank order of relaxing
      potency was comparable to that of the contractile potency of agonists. Also, the
      relaxing effects of APnA were blunted by 10 microM pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonic acid and after exposure to alpha,beta-meATP. In vitro
      and in vivo sympathectomy with 6-hydroxydopamine and removal of the endothelium
      did not modify the effects of APnA in MrA. Thus, the contractile effects of APnA
      in resistance arteries 1) are due to a P2X purinoceptor-mediated stimulation of
      the smooth muscle; 2) depend on the length of the phosphate chain; and 3) are
      followed by endothelium-independent relaxing effects in MrA but not SEA, which
      may involve receptors that are similar to those mediating contraction. The
      regional heterogeneity of APnA effects cannot be attributed to a direct
      neurogenic influence.

PMID- 10945875
TI  - Heterogenous vascular effects of AP5A in different rat resistance arteries are
      due to heterogenous distribution of P2X and P2Y(1) purinoceptors.
AB  - In the accompanying article, we showed that AP5A displayed heterogenous
      vasoactive effects in rat resistance arteries. It induced a stable
      vasoconstriction in the superior epigastric artery (SEA) and a transient
      vasoconstriction in the mesenteric resistance artery (MrA). In the phenylephrine
      precontracted MrA AP5A induced a marked vasorelaxation. In this study the
      noncompetitive inhibition of the AP5A-induced vasoconstriction with pyridoxal
      phosphate-6-azophenyl-2',4'-disulphonic acid was found to be significantly
      stronger in MrA than in SEA. The nonselective P2 purinoceptor antagonist suramin
      inhibited AP5A-induced vasoconstriction in MrA only. The vasoconstriction by the
      P2X purinoceptor agonist alpha,beta-methylene ATP was inhibited by with pyridoxal
      phosphate-6-azophenyl-2',4'-disulfonic acid and suramin similarly to that induced
      by AP5A. Thus, the AP5A-induced vasoconstriction is due to P2X receptor
      activation, but two different P2X receptors seem to be operational in the two
      different vessels. The AP5A-induced vasorelaxation of phenylephrine-precontracted
      MrA was inhibited by the P2Y(1) receptor antagonist ADP3'5'. The vasorelaxation
      induced by ADPbetaS (P2Y(1) agonist) also was inhibited by ADP3'5'. These
      findings suggest that AP5A-induced vasorelaxation of MrA is caused by P2Y(1)
      receptor activation. The P1 (A(2)) receptor antagonist 3, 7-dimethyl-1
      propargylxanthine only slightly inhibited AP5A-induced vasorelaxation at high
      concentrations. Adenosine and the A(2) receptor agonist CGS21680 failed to
      produce significant vasorelaxation. Therefore, vasorelaxation in MrA does not
      involve A(2) purinoceptor activation. AP5A-induced vasorelaxation was not
      inhibited by Ca(2+)- or ATP-dependent K(+) channel blockade with clotrimazole,
      apamin, or glibenclamide. These data indicate that vasoconstriction in MrA and
      SEA by AP5A is due to different P2X receptors, and vasorelaxation in
      precontracted MrA is due to P2Y(1) receptor activation.

PMID- 10945876
TI  - Inhibition of extracellular signal-regulated kinase suppresses endotoxin-induced
      nitric oxide synthesis in mouse macrophages and in human colon epithelial cells.
AB  - Macrophages produce large amounts of nitric oxide (NO) in response to
      proinflammatory cytokines and lipopolysaccharide (LPS) by expressing inducible
      isoform of NO synthase (iNOS). We examined the role of extracellular signal
      regulated kinase p42/44(MAPK) (Erk1/2) in signal transduction pathways leading to
      induction of NO synthesis in response to LPS in J774 mouse macrophages and T-84
      human colon epithelial cells. LPS activated Erk1/2 and induced iNOS and
      subsequent NO production. Erk1/2 activation was inhibited by PD 98059, a specific
      inhibitor of mitogen-activated protein kinase kinase (Mek) that is an upstream
      activator of Erk1/2. At corresponding concentrations PD 98059 reduced LPS-induced
      NO formation by 40 to 50% by inhibiting iNOS expression in J774 and T-84 cells.
      Inhibition of iNOS expression was not mediated by nuclear factor-kappaB because
      PD 98059 had no effect on nuclear factor-kappaB activity in J774 macrophages. In
      addition, PD 98059 reduced LPS-induced L-arginine transport into the cells as
      measured in J774 macrophages, whereas the availability of tetrahydrobiopterin was
      not a limiting factor in NO production after PD 98059. Our results indicate that
      Erk1/2 activation mediates up-regulation but is not essential for LPS-induced
      iNOS expression.

PMID- 10945878
TI  - Consequence of exercise on the cardiovascular effects of l-propranolol in
      spontaneously hypertensive rats.
AB  - The aim of this study was to elucidate time dependence in the development of
      rebound effect and to quantify the cardiovascular effects of chronic l
      propranolol infusions in spontaneously hypertensive rats. Heart rate and systolic
      and diastolic blood pressures were monitored both during exercise performance and
      later by using telemetry. The pharmacodynamics were determined after different
      infusion lengths of l-propranolol (4 mg/kg/day) or placebo for 4, 8, or 12 days.
      A pronounced reduction in heart rate over time was found, which was interpreted
      as a positive influence of exercise on heart rate and was less marked in drug
      treated animals. A mechanism-based model that accounts for competitive
      antagonism, spare receptors, the positive influence of exercise on heart rate,
      and circadian variations was used to describe the data. An empirical effect
      compartment model with an E(max) model was related to a circadian baseline and
      describes the relationship between plasma concentrations and reduction in blood
      pressures. The potencies for exercise and postexercise systolic blood pressure
      were similar with EC(50) values of 48 and 56 ng/ml, and the corresponding maximal
      effects were 17.8 and 21.9%, respectively. The EC(50) values and maximal effects
      for diastolic blood pressure were 26 and 5 ng/ml and 20.6 and 21.0%,
      respectively. The effect of l-propranolol could be quantified by a mechanism
      based model in the presence of a positive influence of exercise on the heart
      rate. The effect of l-propranolol on the blood pressures is best described by an
      effect compartment model with circadian variations.

PMID- 10945877
TI  - BU48: a novel buprenorphine analog that exhibits delta-opioid-mediated
      convulsions but not delta-opioid-mediated antinociception in mice.
AB  - N-Cyclopropylmethyl-[7alpha,8alpha,2', 3']-cyclohexano-1'[S]-hydroxy-6,14-endo
      ethenotetrahydronororip avine (BU48) is a novel, ring-constrained analog of
      buprenorphine. In vivo, BU48 (0.1-10 mg/kg s.c.) produced brief, nonlethal
      convulsions in mice followed by brief Straub tail and a short period of catalepsy
      characteristic of BW373U86 and other nonpeptidic delta-receptor agonists. BU48
      induced convulsions were sensitive to antagonism by naltrindole (10 mg/kg s.c.)
      and were also prevented by administration of the putative delta(1) antagonist 7
      benzylidenenaltrexone and the putative delta(2) antagonist naltriben, with the
      latter being more potent. In the abdominal stretch assay in the mouse, only low
      efficacy antinociceptive activity of BU48 (0.1-10 mg/kg) was seen. This was
      reversed by the kappa-opioid antagonist norbinaltorphimine (32 mg/kg s.c.) but
      not by the delta-opioid antagonist naltrindole (10 mg/kg s.c.). BU48 (10 mg/kg
      s.c.) acted as a delta-antagonist in this assay. In mouse brain homogenates, BU48
      had high (nanomolar) binding affinity for all three opioid receptors in the order
      mu > delta = kappa. In vitro, the compound acted as a potent (EC(50) = 1.4 nM)
      kappa-opioid agonist in the guinea pig ileum and a potent (EC(50) = 0.2 nM) delta
      opioid agonist in the mouse vas deferens but showed partial agonist activity at
      the rat cloned delta-opioid (40%) and human cloned kappa-opioid (59%) receptors
      with very low efficacy at the rat cloned mu-opioid receptor (10%); findings
      consistent with its in vivo profile. BU48 is the first described compound that
      produces delta-opioid-mediated convulsions without any evidence of delta-opioid
      mediated antinociception and will be a useful tool in investigations of the delta
      opioid receptor.

PMID- 10945880
TI  - Inhibition of [(3)H]thymidine transport is a nonspecific effect of PDMP in
      primary cultures of mouse epidermal keratinocytes.
AB  - Inhibitors of sphingolipid metabolism are frequently used to investigate the role
      of ceramide and other sphingolipids as intracellular signaling molecules. For
      example, the inhibitor of glucosylceramide synthase D-threo-1-phenyl-2
      decanoylamino-3-morpholino-1-propanol (PDMP) is commonly used to deplete
      glycosphingolipids and increase ceramide levels. Ceramide is known to induce
      growth arrest and differentiation of keratinocytes, and we hypothesized that PDMP
      would increase ceramide levels and induce growth arrest of primary cultures of
      mouse epidermal keratinocytes. As expected, PDMP increased ceramide levels and
      decreased the incorporation of [(3)H]thymidine into DNA, but surprisingly, PDMP
      was found to rapidly inhibit the intracellular transport of [(3)H]thymidine. This
      is likely due to a direct effect on nucleoside transport by PDMP and not due to
      elevations in ceramide levels because increasing ceramide levels by the addition
      of exogenous sphingomyelinase had no effect on [(3)H]thymidine transport.
      Furthermore, it is unlikely that the decreased [(3)H]thymidine transport is in
      response to growth arrest because PDMP had no effect on the cell cycle profile of
      keratinocytes. These results reveal that PDMP inhibits nucleoside transport
      independent of effects on ceramide levels or cell growth but probably by a direct
      effect on the nucleoside transport apparatus. Thus, this compound may be
      unsuitable for investigating the role of ceramide or other sphingolipids in some
      cellular processes.

PMID- 10945879
TI  - Cannabinoid properties of methylfluorophosphonate analogs.
AB  - Methylarachidonylfluorophosphonate (MAFP) and related analogs have been shown to
      inhibit fatty acid amidohydrolase activity (FAAH), the enzyme responsible for
      hydrolysis of the endogenous cannabinoid ligand anandamide. To fully characterize
      this class of compounds, methylfluorophosphonate compounds with saturated alkyl
      chains ranging from C8 to C20 along with C20 unsaturated derivatives were
      synthesized and evaluated for their ability to interact with the CB1 receptor,
      inhibit FAAH, and produce in vivo pharmacological effects. These analogs
      demonstrated widely varying affinities for the CB1 receptor. Of the saturated
      compounds, C8:0 was incapable of displacing [(3)H]CP 55,940 binding, whereas
      C12:0 exhibited high affinity (2.5 nM). The C20:0 saturated analog had low
      affinity (900 nM), but the introduction of unsaturation into the C20 analogs
      restored receptor affinity. However, none of the analogs were capable of fully
      displacing [(3)H]CP 55,940 binding. On the other hand, all compounds were able to
      completely inhibit FAAH enzyme activity, with the C20:0 analog being the least
      potent. The most potent FAAH inhibitor was the short-chained saturated C12:0,
      whereas the other analogs were 15- to 30-fold less potent. In vivo, the C8:0 and
      C12:0 analogs were highly potent and fully efficacious in producing
      tetrahydrocannabinol (THC)-like effects, whereas the other analogs were either
      inactive or acted as partial agonists. None was capable of attenuating the
      agonist effects of THC. Conversely, the C20:0 analog potentiated the effects of
      anandamide but not those of 2-arachidonoyl-glycerol and THC. The high in vivo
      potency of the novel short-chain saturated MAFP derivatives (C8:0 and C12:0)
      underscores the complexity of manipulating the endogenous cannabinoid system.

PMID- 10945881
TI  - Ageism is a women's issue.

PMID- 10945883
TI  - The older woman: ethnicity and health.
AB  - This article on minority women populations and health care seeks to address the
      economic impact of health care for such populations, discuss the scope of the
      problem surrounding women's health, address the health status of minority older
      women, identify ethnocultural strategies and nursing implications for the health
      care of older women from varying ethnic backgrounds, and provide resources to
      assist health care providers.

PMID- 10945882
TI  - Women's health in the 21st century.
AB  - This century's first year is a good time to reflect on the health status of
      women. Technology and information have exploded in the past 30 years and show no
      signs of abating. We are entering a new century with some of the same problems
      that faced us in 1900. Uncontrollable infectious diseases, unacceptable morbidity
      and mortality rates for diseases that disproportionately affect women, and a
      continuing lack of funded research and reimbursement for health promotion leave
      women in a precarious position. Which issues are critical to address, and which
      technologies may be used to further improve our delivery of health care?

PMID- 10945885
TI  - Public policy and older women's health.
AB  - This article provides an overview of the aging of our population and its
      implications for women and the nursing profession in general. A brief history of
      women's role in the legislative and policy arena is provided along with a brief
      synopsis of legislative initiatives introduced in the 105th and 106th Congress
      and suggestions for nursing intervention.

PMID- 10945884
TI  - Domestic violence and aging women.
AB  - Domestic violence against women is a significant health problem in this country
      and worldwide. A group that has been neglected, however, in discussions of this
      problem are older women. Although one might assume that domestic violence against
      older women is included in discussions of elder abuse, that body of literature
      actually may obscure the problem for several reasons. This article discusses the
      background of domestic violence against older women in two contexts: long
      standing wife abuse and abuse of aging caregivers. Suggestions for assessment and
      intervention are included.

PMID- 10945887
TI  - Marge Drugay, ND, RNC, women's health advocate.

PMID- 10945888
TI  - Making the most of quality indicator information.
AB  - With quality of care and quality of life as the focus of payers, accreditation
      bodies, regulators, customers, and providers alike, the use of quality indicator
      data available as part of the case mix system presents an opportunity for an
      effectively focused effort toward continuous clinical quality improvement. With a
      regular and systematic review, analysis, and follow-up process, providers are
      able to use quality indicators to identify and address the areas of most
      significance to their specific population. And because the system is common to
      all providers, the ability to compare outcomes and bring best practice efforts to
      light is becoming more readily available.

PMID- 10945886
TI  - Physical activity maintenance in elders with cardiac problems.
AB  - Clinicians who work with elderly people after acute cardiac events need
      strategies to facilitate the continuance of physical activity learned in cardiac
      rehabilitation programs. This exploratory study examined three factors related to
      this maintenance in 31 men and women: self-efficacy, stages of change, and social
      support for exercise. Self-efficacy was significantly correlated to stages of
      change and physical activity. Clinicians can use these factors to develop
      strategies to enhance the maintenance of exercise in elders with cardiac
      problems.

PMID- 10945889
TI  - Information exchange: critical connections to older adult decision-making during
      health care transitions.

PMID- 10945890
TI  - New developments in osteoporosis treatments.

PMID- 10945891
TI  - Pain assessment in the home. Part 2.

PMID- 10945892
TI  - Focus on fluids.

PMID- 10945893
TI  - Acute blockade of nitric oxide synthesis induces disorganization and amplifies
      lesion-induced plasticity in the rat retinotectal projection.
AB  - In the rat visual system, the uncrossed retinotectal projection undergoes a
      topographical refinement within the first two postnatal weeks. We have studied
      the role of nitric oxide (NO), a retrograde messenger which couples pre- and
      postsynaptic activation, in the development of the uncrossed retinotectal
      projection and in the plasticity of this pathway as a result of a restricted
      retinal lesion in the opposite eye. During development, maximal nitric oxide
      synthase (NOS) activity was observed in homogenates of tectal tissue at postnatal
      day 5 (PND 5), followed by a two-step decrease at the end of the topographical
      fine tuning period (PND 21) and the adult stage (PND 42). We also tested the
      effects of an acute in vivo blockade of NOS during the development of both
      animals that had not been operated on, and lesioned animals. Animals ranging from
      PND 4 to PND 42 were treated either with the NOS inhibitor, L-nitro-arginine
      (Narg 50 mg/kg ip.) or vehicle (NaCl 0.9%) during 4 days (from PND 4-7 or PND 9
      12) or 8 days (from PND 20-27 or PND 34-41). Reduction of NOS activity induced
      sprouting of the ipsilateral pathway up to the second postnatal week in the
      animals that had not been operated on. Rats that had been operated on, however,
      showed an amplification of the lesion-induced plasticity up to the fourth
      postnatal week under NOS blockade. The data suggest that NO plays a role in the
      stabilization of retinotectal synapses during the critical period of topographic
      refinement, and indicate that an acute blockade of retrograde signals enables
      plastic rearrangements in the visual system within this time window.

PMID- 10945894
TI  - Axolemmal repair requires proteins that mediate synaptic vesicle fusion.
AB  - A damaged cell membrane is repaired by a seal that restricts entry or exit of
      molecules and ions to that of the level passing through an undamaged membrane.
      Seal formation requires elevation of intracellular Ca(2+) and, very likely,
      protein-mediated fusion of membranes. Ca(2+) also regulates the interaction
      between synaptotagmin (Syt) and syntaxin (Syx), which is thought to mediate
      fusion of synaptic vesicles with the axolemma, allowing transmitter release at
      synapses. To determine whether synaptic proteins have a role in sealing axolemmal
      damage, we injected squid and crayfish giant axons with an antibody that inhibits
      squid Syt from binding Ca(2+), or with another antibody that inhibits the Ca(2+)
      dependent interaction of squid Syx with the Ca(2+)-binding domain of Syt. Axons
      injected with antibody to Syt did not seal, as assessed at axonal cut ends by the
      exclusion of extracellular hydrophilic fluorescent dye using confocal microscopy,
      and by the decay of extracellular injury current compared to levels measured in
      uninjured axons using a vibrating probe technique. In contrast, axons injected
      with either denatured antibody to Syt or preimmune IgG did seal. Similarly, axons
      injected with antibody to Syx did not seal, but did seal when injected with
      either denatured antibody to Syx or preimmune IgG. These results indicate an
      essential involvement of Syt and Syx in the repair (sealing) of severed axons. We
      suggest that vesicles, which accumulate and interact at the injury site, re
      establish axolemmal continuity by Ca(2+)-induced fusions mediated by proteins
      such as those involved in neurotransmitter release.

PMID- 10945895
TI  - Ionic currents of Drosophila embryonic neurons derived from selectively cultured
      CNS midline precursors.
AB  - In order to investigate the electrogenesis of defined cell populations, we
      applied an in vitro system that allows the selective culturing of individual
      Drosophila CNS precursors under different conditions. CNS midline (ML) precursors
      prepared from gastrula stage embryos gave rise to progeny cells with neuronal and
      glial morphology that expressed specific markers. Using whole-cell patch-clamp
      recordings, a detailed description of ionic currents present in this defined cell
      population is provided. Most ionic currents of cultured ML neurons were similar
      to other cultured Drosophila neurons, even though their embryonic origin is
      different. They displayed at least two voltage-gated potassium currents, a
      voltage-gated sodium, two voltage-gated calcium currents, and responded to the
      neurotransmitters ACh and GABA. They showed homogeneity in action potential
      firing properties, generating only a single spike even upon sustained
      depolarization. Interestingly, although the expression of the voltage-gated
      potassium currents appeared to be highly cell autonomous, for all other currents
      significant changes were observed in the presence of fiber contacts.

PMID- 10945896
TI  - Seasonal changes in neuron numbers in the hippocampal formation of a food
      hoarding bird: the black-capped chickadee.
AB  - The volume of the hippocampal formation (HF) in black-capped chickadees (Poecile
      atricapillus) varies across the seasons, in parallel with the seasonal cycle in
      food hoarding. In this study, we estimate cell density and total cell number in
      the HF across seasons in both juveniles and adults. We find that the seasonal
      variation in volume is due to an increase in the number of small and large cells
      (principally neurons) in the fall. Adults also have lower neuron densities than
      juveniles. Both juveniles and adults show an increase in cell density in the
      rostral part of the HF in August and a subsequent decrease toward October. This
      suggests that the net cell addition to the HF may already start in August. We
      discuss the implications of this early start with respect to the possibility that
      the seasonal change in HF volume is driven by the experience of food hoarding. We
      also speculate on the functional significance of the addition of neurons to the
      HF in the fall.

PMID- 10945897
TI  - Neurogenesis in the vomeronasal epithelium of adult rats: evidence for different
      mechanisms for growth and neuronal turnover.
AB  - The pattern of cell migration during neuronal turnover in the vomeronasal sensory
      epithelium (VN-SE) is controversial. In mice, proliferating cells were detected
      at the edges and were described as migrating to the center of the VN-SE. In rats,
      in addition to proliferating cells at the margins of the epithelium, dividing
      cells are also present along the entire basal lamina of the VN-SE. In marsupials,
      dividing cells have also been observed in the margins and in the center of the VN
      SE, the latter of which migrate vertically and become neurons. To investigate
      whether the process of neuronal turnover in placental mammals consists of
      horizontal and/or vertical migration, and whether or not this process is common
      to mammals, adult rats were injected with bromodeoxyuridine (BrdU) and allowed to
      survive for different periods of time. The distribution of BrdU-labeled cells in
      the horizontal and vertical dimension of the VN-SE was analyzed as a function of
      time. Both horizontal and vertical migrations of BrdU-labeled cells were
      detected. Since cells in the center of the VN-SE migrate vertically, and, as
      demonstrated by coexpression of markers of neuronal maturity and BrdU, become
      mature one day after undergoing mitosis, it is very likely that these cells
      participate in neuronal turnover. Conversely, because cells in the margins of the
      VN-SE stop migrating horizontally on day 14 before they have reached the center
      of the VN-SE, and since the VN-SE continues to grow during adulthood, it is
      likely that most of these latter cells constitute pools for growth.

PMID- 10945898
TI  - Agrin fragments differentially induce ectopic aggregation of acetylcholine
      receptors in myotomal muscles of Xenopus embryos.
AB  - Agrin is an extracellular synaptic protein that organizes the postsynaptic
      apparatus, including acetylcholine receptors (AChRs), of the neuromuscular
      junction. The COOH-terminal portion of agrin has full AChR-aggregating activity
      in culture, and includes three globular domains, G1, G2, and G3. Portions of the
      agrin protein containing these domains bind to different cell surface proteins of
      muscle cells, including alpha-dystroglycan (G1-G2) and heparan sulfate
      proteoglycans (G2), whereas the G3 domain is sufficient to aggregate AChRs. We
      sought to determine whether the G1 and G2 domains of agrin potentiate agrin
      activity in vivo, as they do in culture. Fragments from the COOH-terminal of a
      neuronal agrin isoform (4,8) containing G3, both G2 and G3, or all three G
      domains were overexpressed in Xenopus embryos during neuromuscular synapse
      formation in myotomal muscles. RNA encoding these fragments of rat agrin was
      injected into one-cell embryos. All three fragments increased the ectopic
      aggregation of AChRs in noninnervated regions near the center of myotomes.
      Surprisingly, ectopic aggregation was more pronounced after overexpression of the
      smallest fragment, which lacks the heparin- and alpha-dystroglycan-binding
      domains. Synaptic AChR aggregation was decreased in embryos overexpressing the
      fragments, suggesting a competition between endogenous agrin secreted by nerve
      terminals and exogenous agrin fragments secreted by muscle cells. These results
      suggest that binding of the larger agrin fragments to alpha-dystroglycan and/or
      heparan sulfate proteoglycans may sequester the fragments and inhibit their
      activity in embryonic muscle. These intermolecular interactions may regulate
      agrin activity and differentiation of the neuromuscular junction in vivo.

PMID- 10945899
TI  - Distraction index, part II: inflammation in nongynecologic cytology.

PMID- 10945901
TI  - Cytomorphology of gastrointestinal stromal tumor: diagnostic role of aspiration
      cytology, core biopsy, and immunochemistry.
AB  - Gastrointestinal stromal tumors (GISTs) comprise a heterogeneous group of
      neoplasms of the gastrointestinal tract previously referred to as leiomyomas,
      leiomyosarcomas, or schwannomas. GISTs derive from the interstitial cell of Cajal
      and, in addition to variable expression of smooth muscle and neural markers, they
      characteristically express CD34 and CD117. To our knowledge, the cytologic
      appearance of gastric neoplasms designated as GISTs has never been reported. We
      illustrate the fine-needle aspiration (FNA) cytology findings of a gastric
      stromal tumor having spindle cells with delicate cytoplasm and prominent nuclear
      palisading. Consistent core biopsy and immunochemistry findings further supported
      the diagnosis of GIST. Pathologic evaluation of the resected tumor confirmed the
      cytologic diagnosis. In the appropriate clinical and radiologic setting, a
      confident diagnosis of GIST can be established by FNA cytology and core biopsy.
      The roles of immunochemical stains and other ancillary techniques in reaching the
      correct diagnosis are addressed.

PMID- 10945900
TI  - Use of a novel marker, calponin, for myoepithelial cells in fine-needle aspirates
      of papillary breast lesions.
AB  - Benign and malignant papillary lesions of the breast (PBL) can be difficult to
      distinguish in fine-needle aspirates (FNA). This study evaluates the use of
      smooth muscle actin (SMA) and a new smooth muscle-specific protein, calponin, for
      identifying myoepithelial cells (MEC) by immunohistochemical methods in paraffin
      embedded cell blocks of FNA of PBL. Formalin-fixed, paraffin-embedded cell blocks
      of 40 cases of PBL were stained using SMA and calponin, steam heat-induced
      epitope retrieval, and an avidin biotin-complex technique. Staining was evaluated
      in MEC, epithelial, and stromal cells. The diagnosis of benign vs. malignant
      papillary lesion was made by using cytomorphological criteria and the
      presence/absence of MEC in the cell block. These results were compared to the
      original cytologic and subsequent histologic diagnoses. Of 40 cases of FNA
      diagnosed as PBL, there were 27 intraductal papillomas (IP), 6 papillary lesions
      with atypical features (PLAF), and 7 papillary carcinomas (PC). In all of the IP,
      MEC stained both with SMA and calponin. None of the PC cases was positive for MEC
      with calponin, and 2 out of 7 cases were weakly positive by SMA. In 6 cases of
      PLAF, 2 were negative for MEC, both by SMA and calponin, and a malignant
      papillary lesion was confirmed by histology. The remaining 4 cases were positive
      for MEC with both markers and were confirmed to be benign by histology. SMA
      stained stromal cells strongly in all of the cases where stroma was present (18
      of a total of 40 cases of PBL), while calponin stained stroma focally in only 7
      cases. More than half of all cases had nuclear staining of epithelial cells with
      SMA; calponin did not show any nuclear staining.

PMID- 10945902
TI  - Cytologic findings in cervical smears in patients using intramuscular
      medroxyprogesterone acetate (Depo-provera) for contraception.
AB  - The purpose of the present study was to assess the findings in cervical smears
      associated with intramuscular depot medroxyprogesterone acetate (Depo-Provera)
      contraception. Seventy-four cervical smears of reproductive-age patients on Depo
      Provera were reviewed for cytologic abnormalities, predominant cell type, and
      intermediate cell glycogenation (extensive (EGly) = navicular cells /
      glycogenation in 10 or more high-powered fields (hpf); moderate (MGly) = 5-10
      hpf; and focal (FGly) = less than 5 hpf). A control group of 38 nonpregnant
      patients without hormonal therapy was reviewed. Study group patients' (SGP) age
      ranged from 16-44 years (average 28.1); control group patients (CGP) from 17-42
      years (average 29.4). Time since last menstrual period (LMP) for the SGP was 16.9
      months (range 1-96); LMP for CGP was 18.2 days (range 5-33). Four (5.4%) SGP had
      squamous intraepithelial lesions (SIL), four (5.4%) atypical squamous cells of
      undetermined significance (ASCUS), and one (1.4%) atypical repair. No CGP had SIL
      or ASCUS. Seventy-three (98.6%) SGP had intermediate cell (IC) predominance; one
      had parabasal cell predominance. Of the CGP, 28 (73.7%) had IC predominance, nine
      (23.7%) superficial cell (SC) predominance and one (2.6%) had near equal IC and
      SC. EGly was seen in 22 (29.7%) SGP; two (5.3%) in CGP (chi-square 7.53; 0.95 =
      3.84). MGly was seen in 29 (39.2%) SGP; 10 (26.3%) in CG. FGly was seen in 17
      (22.9%) SGP; 14 (36.8%) in CGP. No glycogenation was seen in six (8.1%) SGP; 12
      (31.6%) in CGP. Time since LMP was inversely proportional to glycogenation in
      SGP: EGly-LMP 11.6 months; MGly-LMP 14.9 months; FGly-LMP 15.0 months; and no
      glycogenation-LMP 22.5 months. Glycogenation of IC appears inversely proportional
      to Depo-Provera effect. EGly due to recent Depo-Provera administration mimics
      changes associated with pregnancy.

PMID- 10945903
TI  - Use of computer-assisted rescreening as an ancillary tool to subclassify AGUS
      cervical smears.
AB  - A substantial percentage of women with a diagnosis of atypical glandular cells of
      undetermined significance (AGUS) on cervical smears harbor a significant squamous
      or glandular, preneoplastic or neoplastic lesion on subsequent follow-up.
      Attempts to subclassify AGUS smears by conventional methods have had mixed
      results. To determine whether subclassification of AGUS cervical smears using
      computer-assisted rescreening based on the neural network would improve
      correlation with subsequent histologic follow-up, 91 cervical smears,
      conventionally diagnosed as AGUS without concomitant squamous lesions, were
      subjected to analysis by a computer-assisted automated screening system. Computer
      generated images were evaluated by a cytotechnologist without the knowledge of
      the histologic outcomes. Prior to manual review, each case was classified as
      either within normal limits, no review required; or abnormal, review required.
      Based on the degree of abnormality, the latter category was further subclassified
      into either low probability or high probability of abnormality. The results of
      the computer-assisted reclassification were then compared with the histologic
      follow-up of all patients. Thirty-three cases (38.8%) had a significant lesion on
      histologic follow-up. The lesions included 4 CIN I, 7 CIN II/III, 12 endocervical
      adenocarcinomas (ACA), and 10 endometrial ACA. Based on computer-generated
      images, 65% of the smears that were triaged as high probability of abnormality,
      11.5% that were triaged as low probability of abnormality, and 10.5% that were
      triaged as within normal limits had a significant lesion on subsequent follow-up.
      We conclude that computer-assisted rescreening aids in the triage of AGUS smears
      and that computer-assisted rescreening based on the neural network or other
      algorithms may be a useful ancillary tool for subclassifying AGUS cervical
      smears.

PMID- 10945904
TI  - Neural network-based digitized cell image diagnosis of bladder wash cytology.
AB  - In this pilot study, we tested whether it is possible to apply neural network
      based diagnostics on bladder washings to detect urothelial cell carcinoma of the
      bladder. Eighty-five bladder wash (BW) samples were chosen at random from our own
      database. Cystoscopy, histology, and follow-up data concerning tumor recurrence
      were available. Each slide was scanned by the neural network-based digitized cell
      image system. The neural network-based diagnosis (NNBD) was based on 128
      digitized cell images provided by the system. The light microscopic diagnosis
      (LMD) was rendered by an experienced cytopathologist using the same terminology,
      i.e., negative, low-grade tumor, and high-grade tumor. Finally, an automatic
      QUANTICYT analysis was performed on the same material, with as classification
      low, intermediate, and high risk. The sensitivity for diagnosing a histologically
      confirmed tumor was for NNBD 92%, for LMD 50%, and for QUANTICYT 69%. For the
      three methods, receiver operating characteristic (ROC) curves were made for the
      thresholds low grade/intermediate risk and high grade/high risk. For the
      prediction of a positive cystoscopy, the highest area under the curve (AUC) was
      found for NNBD, being 0.71. The AUC for LMD was 0.58. QUANTICYT analysis had the
      highest AUC value (0.62) for predicting tumor recurrence after a negative
      cystoscopy, with a lower value for NNBD (0.50). These findings indicate that
      neural network-based diagnosis of bladder washing samples is highly promising.

PMID- 10945905
TI  - Cytology of small-cell carcinoma arising in Barrett's esophagus.
AB  - The cytologic and histologic features of a rare case of small-cell carcinoma
      arising in Barrett's esophagus are reported. The patient presented with
      progressive dysphagia and an endoscopy revealed a distal esophageal mass with
      luminal constriction. The brushing smears showed small-cell carcinoma and
      dysplastic glandular epithelium. The concomitant biopsy confirmed the diagnosis
      of small-cell carcinoma arising in Barrett's esophagus.

PMID- 10945906
TI  - Duodenal carcinoid tumor: report of a case diagnosed by endoscopic ultrasound
      guided fine-needle aspiration biopsy with immunocytochemical correlation.
AB  - Fine-needle aspiration biopsy is a reliable and accurate method for the
      endoscopic diagnosis of gastrointestinal malignancies and it is particularly well
      suited for evaluation of submucosal lesions. We report the cytopathologic
      findings of a case of malignant carcinoid tumor of a 44-year-old male who
      presented with melena and a nonhealing duodenal ulcer. Endoscopic ultrasound
      examination revealed a submucosal lesion in the pyloric region. Fine-needle
      aspiration revealed abundant cellularity with tumor cells arranged in sheets and
      loose groups and dispersed single cells in a clean background. Papillary
      fragments, capillaries cuffed by tumor cells, and rosette formation were also
      noted. The cells were moderate in size, round to oval, with a small subpopulation
      of spindle-shaped cells. The nuclei were uniform, round to oval, with smooth
      nuclear borders. The chromatin pattern was finely granular with a salt-and-pepper
      appearance. The cytoplasm of the cells was small to moderate in amount, pale, and
      showed fine granularity. The differential diagnosis included a neuroendocrine
      neoplasm vs. an epithelioid gastrointestinal stromal tumor. The tumor cells were
      focally positive for chromogranin and negative for CD34, supporting the diagnosis
      of a neuroendocrine neoplasm. The differential diagnosis of primary
      gastrointestinal carcinoid tumors from gastrointestinal stromal tumors can be
      very difficult in cytologic material. In cases when diagnostic material is scant,
      or only present on one smear, the use of smear division and cell transfer in
      order to perform immunocytochemical stains may be of considerable value to
      confirm the neuroendocrine nature of the neoplasms.

PMID- 10945907
TI  - Fine-needle aspiration cytology of hemangiopericytoma: report of two cases.
AB  - The fine-needle aspiration biopsy (FNAB) findings in two cases of
      hemangiopericytoma (HP), arising in the parotid gland and on the inner chest
      wall, respectively, are reported. Smear preparations in each case showed
      cytologic features of an undifferentiated spindle-cell neoplasm, whereas a core
      needle biopsy specimen of the chest wall mass showed a spindle-cell tumor with a
      "staghorn-like" arrangement of endothelium-lined vascular channels. Immunostains
      performed on this core biopsy, and on the surgical resection specimens in both
      cases, showed positive staining of tumor cells for vimentin and CD34, with
      negative staining for a variety of smooth muscle, epithelial, neural, and
      neuroendocrine markers. Electron microscopy performed in one case further
      supported the diagnosis of HP. With adequate sampling and appropriate use of
      ancillary studies, a diagnosis of HP can be reliably suggested on the basis of
      FNAB and core biopsy of a soft-tissue mass.

PMID- 10945908
TI  - Epithelioid angiomyolipoma: appearance on fine-needle aspiration report of a
      case.
AB  - Epithelioid angiomyolipoma is a recently recognized clinicopathologic entity
      first described by Martignoni et al. in 1995. Since then, several articles have
      further clarified its histogenesis and histologic features. Due to the presence
      of polygonal cells with voluminous cytoplasms, this neoplasm is often mistaken
      for renal-cell carcinoma. In this case presentation, we describe the cytologic
      features of an epithelioid angiomyolipoma obtained by fine-needle aspiration. The
      histogenesis and how it relates to diagnosis is briefly discussed. The importance
      of ancillary techniques in the differential diagnosis of epithelioid cells
      obtained in a renal aspirate is reviewed.

PMID- 10945909
TI  - Cytohistologic features of invasive micropapillary carcinoma in a young female.
AB  - Invasive micropapillary carcinoma (IMPC) is a recently reported variant of breast
      carcinoma in women. There has been only a single report describing the cytologic
      features of IMPC in the literature. We report on the cytohistologic features of
      IMPC with diffuse involvement of two quadrants of the breast and axillary lymph
      node metastases in a 32-yr-old female. The cytologic appearance of IMPC was
      characterized by high cellularity, marked cell discohesion, and epithelial cells
      forming aggregates, morules, and angular and papillary clusters without
      fibrovascular cores and showing high nuclear/cytoplasmic ratio, irregular nuclear
      contours, and finely stippled chromatin. Occasional psammoma bodies were noted.
      Histologic examination showed a pure IMPC composed of clusters, morules, and
      aggregates of malignant epithelial cells surrounded by distinctly clear spaces
      separated by thin fibrovascular septa. The tumor involved both inner quadrants
      and axillary lymph nodes. A primary tumor elsewhere, particularly in the ovaries,
      was excluded. The patient has been disease-free 38 mo after the initial
      diagnosis.

PMID- 10945910
TI  - Metastatic, sarcomatoid, and PSA- and PAP-negative prostatic carcinoma: diagnosis
      by fine-needle aspiration.
AB  - Fine-needle aspiration of prostatic carcinoma usually yields an acinar carcinoma
      that is immunoreactive for prostatic-specific antigen (PSA) and prostatic acid
      phosphatase (PAP). We report on two FNAs of metastatic sarcomatoid prostatic
      carcinoma that were PSA- and PAP-negative. Our methods included a review of the
      medical records and pathology results. Both cases presented with elevated serum
      PSA levels and prostate needle biopsies with Gleason score 8 and 9 tumors,
      respectively. Both cases developed retroperitoneal/pelvic lymphadenopathy, and
      fine-needle aspirations were performed. These showed high-grade, sarcomatoid
      tumors with marked anisonucleosis. Immunocytochemical staining for PSA and PAP
      was negative in both cases. Clinical and radiologic evaluation failed to reveal
      any other potential primary sites. Metastatic, sarcomatoid, PSA- and PAP-negative
      prostatic carcinoma is a rare diagnosis of exclusion that should be considered in
      the characteristic clinical setting.

PMID- 10945911
TI  - Diagnostic challenges in the fine-needle aspiration diagnosis of carotid body
      paragangliomas: report of two cases.
AB  - Two cases of carotid body paragangliomas sampled by fine-needle aspiration (FNA)
      cytology prior to other medical diagnostic studies are presented. In the first
      case, the presence of an ipsilateral ulcerative lesion of the nasopharynx along
      with pronounced atypia of the specimen posed a challenge to the correct cytologic
      interpretation, which was initially sidetracked in favor of a metastatic
      epithelial lesion. In the second case, a tumor mass of unusually large size and
      extension which included the pharynx, coupled with a large amount of profusely
      hemorrhagic aspirate, presented a diagnostic problem, which was overcome by
      processing part of the specimen as a cell block, which by its histologic and
      immunochemical features provided a definitive pathologic diagnosis. In handling
      these two clinically complex cases of carotid paraganglioma, two learning
      principles became clear on how to reach a correct FNA diagnosis in such lesions:
      1) The anatomic location of the lateral neck mass with its prolonged history,
      along with a hemorrhagic FNA specimen exhibiting at least some cytologic features
      reminiscent of endocrine neoplasm, are among the factors that help in arriving at
      a suggestive diagnosis of paraganglioma, when other clinical features tend to
      sidetrack from interpretation of the cytologic changes. 2) In the practice of FNA
      cytology, if the possibility of paraganglioma arises, processing part of the
      specimen as a cell block with accompanying histology and immunohistochemistry can
      provide a definitive diagnosis of such lesion.

PMID- 10945912
TI  - Evaluation of cellular residue in the ThinPrep PreservCyt vial.
AB  - The ThinPrep Pap Testtrade mark is a fluid-based method used for the collection
      and preparation of cervicovaginal samples. The collection device(s) is/are rinsed
      in Cytyc's ThinPrep PreservCyt medium and a thin-layer slide is prepared using
      the ThinPrep 2000 automated processor. The purpose of this study was to determine
      the detection rates for cervical lesions utilizing an additional ThinPrep slide.
      Fifty-four cervical samples processed by the ThinPrep method were reviewed. An
      additional thin-layer slide was obtained from the cellular residue for each case
      utilizing a new filter. Case selection criteria included cases with a few
      equivocal cells, a few diagnostic cells, or several low-grade dysplastic cells
      seen on the original ThinPrep slide. The original slides and repeat slides were
      reviewed by two cytopathologists and two cytopathology fellows. Fifty-four
      patients were included in the study, mean age 35 years (range: 16-76). The
      original diagnoses included: 17 negative cases, 22 atypical squamous cells of
      undetermined significance (ASCUS), 10 low-grade squamous intraepithelial lesions
      (LGSILs), four high-grade squamous intraepithelial lesions (HGSILs), and one case
      of atypical glandular cells of undetermined significance (AGUS). On the repeat
      slides the diagnosis remained the same in 42 (77.8%) cases, diagnostic cells were
      not present in 10 (18.5%) cases, fungal elements consistent with candida were
      detected on the repeat smear in one case (1.8%), and higher grade dysplastic
      cells were found in two cases (3.7%). Our study showed that the ThinPrep method
      provides a representative, diagnostic sample on the slide. Repeat processing adds
      little to the overall diagnosis.

PMID- 10945913
TI  - Fine-needle aspiration of idiopathic cystic chondromalacia (pseudocyst of the
      auricle): report of two cases.

PMID- 10945914
TI  - Papillary renal-cell carcinoma demonstrating prominent foamy macrophages by
      cytobrush scrapings: a case report.

PMID- 10945915
TI  - Cytopathology in India.

PMID- 10945917
TI  - Funding for Canadian biomedical research - a ray of hope!

PMID- 10945916
TI  - Follicular carcinoma of the thyroid with extensive clear-cell differentiation: a
      potential diagnostic pitfall.
AB  - Clear-cell features have been recognized in several different thyroid neoplasms.
      A case of thyroid follicular carcinoma with extensive clear- and Hurthle-cell
      features is described in a 37-yr-old white female, with cytochemical and
      immunohistochemical analysis. The tumor of the thyroid gland, with anterior neck
      soft-tissue extension, displayed clear cells on fine-needle aspiration, which
      were negative for thyroglobulin. The surgical specimen displayed predominately
      clear cells (80%), and only the nonclear-cell areas stained for thyroglobulin.
      Proper categorization of clear-cell lesions of the thyroid and soft tissues
      requires a multimodality approach, involving clinical/pathological correlation,
      morphological analysis, and ancillary tissue studies. Immunohistochemical stains
      for thyroglobulin are quite definitive in making the distinction between primary
      clear-cell thyroid tumors vs. metastatic clear-cell tumors. Cytologists should be
      aware, however, that the clear-cell areas of thyroid tumors might not stain for
      thyroglobulin.

PMID- 10945918
TI  - Biotech pharmaceuticals and biotherapy: an overview.
AB  - Broadly, the history of pharmaceutical biotechnology includes Alexander Fleming"s
      discovery of penicillin in a common mold, in 1928, and the subsequent development
      prompted by World War II injuries-of large-scale manufacturing methods to grow
      the organism in tanks of broth. Pharmaceutical biotechnology has since changed
      enormously. Two breakthroughs of the late 1970s became the basis of the modern
      biotech industry: the interspecies transplantation of genetic material, and the
      fusion of tumor cells and certain leukocytes. The cells resulting from such
      fusion-hybridomas-replicate endlessly and can be geared to produce specific
      antibodies in bulk. Modern pharmaceutical biotechnology encompasses gene cloning
      and recombinant DNA technology. Gene cloning comprises isolating a DNA-molecule
      segment that corresponds to a single gene and synthesizing ("copying") the
      segment. Recombinant DNA technology, or gene splicing, comprises altering genetic
      material outside an organism-for example, by inserting into a DNA molecule a
      segment from a very different DNA molecule-and making the altered material
      (recombinant DNA) function in living things. Recombinant DNA technology enables
      modifying microorganisms, animals, and plants so that they yield medically useful
      substances, particularly scarce human proteins (by giving animals human genes,
      for example). This review, however, focuses not on pharmaceutical biotechnology"s
      methods but on its products, notably recombinant pharmaceuticals. It describes
      various types of biotech pharmaceuticals, their safety and effectiveness relative
      to the safety and effectiveness of conventionally produced pharmaceuticals, and
      the regulation of biotech pharmaceuticals.

PMID- 10945919
TI  - An area correction method to reduce intrasubject variability in bioequivalence
      studies.
AB  - PURPOSE: This paper investigates the use of a corrected area (AUC*K) to
      compensate for intrasubject variability in bioequivalence studies. METHODS: Using
      computer simulation, this technique was applied to bioequivalence studies for two
      drugs. Both drugs exhibit first-order absorption and linear one-compartment
      disposition kinetics and total elimination by the liver. Drug I has a low
      intrinsic clearance (Cl(int)) and is not bound to blood components, while Drug II
      has a high Cl(int) and is highly bound. Two-way crossover trials, each including
      24 subjects, were simulated using a spreadsheet program, which also performs
      ANOVA and provides 90% confidence intervals for C(max), AUC and AUC*K. The
      intrasubject CV for the parameter of interest was 30%. For all other
      pharmacokinetic parameters, the intrasubject CVs were 10%. RESULTS: Drug I: With
      high variability in Cl(int), AUC's were concluded to be bioequivalent in 335,
      303, 222, 102 and 32 of 500 trials for mean difference in % absorbed (DeltaA =
      [A(test) -A(ref)]x100/A(ref)), -5%, -10%, -15% and -20% respectively. The
      corresponding numbers of trials that passed for AUC*K were 500, 500, 500, 382 and
      23. Drug II: With high variability in Cl(int), 273, 281, 190, 106 and 29 of 500
      trials passed for AUC at DeltaA of 0%, -5%, -10%, -15% and -20% respectively. The
      corresponding numbers that passed for AUC*K were 378, 351, 239, 113 and 38
      trials. For both drugs, when high variability was assigned to V, area correction
      reduced the number of trials passing for AUC. When the same intrasubject %CV was
      assigned to both Cl and V, area correction resulted in no change (Drug I) or a
      decrease (Drug II) in the number of passing trials. Assigning high intrasubject
      %CV to DeltaA did not appear to alter the outcome of the simulation. CONCLUSION:
      Area correction appears to be helpful only when high intrasubject variability
      exists in clearance and not in the other parameters. It may be more helpful for
      drugs with low, compared to high Cl(int) since in the latter case variability in
      Cl(int) is reflected in both systemic clearance and bioavailability. It is
      recommended that area correction be attempted in bioequivalence studies of drugs
      where high intrasubject variability in clearance is known or suspected. It should
      be avoided where there appears to be a difference in K between treatments. The
      value of this approach in regulatory decision making remains to be determined.

PMID- 10945920
TI  - Transbuccal delivery of acyclovir (II): feasibility, system design, and in vitro
      permeation studies.
AB  - PURPOSE: To design a buccal mucoadhesive system for systemic delivery of
      acyclovir using a novel mucoadhesive, copolymers of acrylic acid and
      poly(ethylene glycol), and to determine the feasibility of transbuccal delivery
      of acyclovir using this system. METHODS: The buccal delivery system was prepared
      using an adhesive, a copolymer of acrylic acid and poly(ethylene glycol)
      monomethylether monomethacrylate, and an impermeable membrane to prevent
      excessive washout by saliva and to attain unidirectional release. Acyclovir was
      loaded into the copolymer film prior to lamination of backing material. In vitro
      drug release studies were conducted in isotonic McIlvaine buffer solution. Buccal
      permeation of acyclovir was investigated using porcine buccal mucosa with side-by
      side flow through diffusion cells at 37;C. Acyclovir was quantified using HPLC.
      RESULTS: Buccal permeation of acyclovir from the mucoadhesive delivery system was
      controlled for up to 20 hours with a time lag (t(lag)) of 10.4 hours and a steady
      state flux of 144.2 microg/cm(2)/h. With the incorporation of NaGC into the
      system t(lag) was shortened to 5.6 hours with an enhanced steady state flux of
      758.7 microg/cm(2)/h. Sustained delivery of acyclovir across bucccal mucosa using
      this mucoadhesive system was maintained for up to 22 hours. CONCLUSIONS: The
      mucoadhesive system of P(AA-co-PEG) was shown to be a good candidate for
      controlled oral mucosal delivery of acyclovir. Buccal delivery of acyclovir was
      proven feasible based on in vitro permeation studies.

PMID- 10945921
TI  - The Raven's progressive matrices: change and stability over culture and time.
AB  - Data relating to the stability and variation in the norms for the Raven's
      Progressive Matrices Test (a well-validated measure of basic cognitive
      functioning) for different cultural, ethnic, and socioeconomic groups on a
      worldwide and within-country basis are first summarized. Subsequent sections deal
      with variation over time. A possible explanation for the variation in norms over
      time and between ethnic groups within countries is offered.

PMID- 10945922
TI  - The unity and diversity of executive functions and their contributions to complex
      "Frontal Lobe" tasks: a latent variable analysis.
AB  - This individual differences study examined the separability of three often
      postulated executive functions-mental set shifting ("Shifting"), information
      updating and monitoring ("Updating"), and inhibition of prepotent responses
      ("Inhibition")-and their roles in complex "frontal lobe" or "executive" tasks.
      One hundred thirty-seven college students performed a set of relatively simple
      experimental tasks that are considered to predominantly tap each target executive
      function as well as a set of frequently used executive tasks: the Wisconsin Card
      Sorting Test (WCST), Tower of Hanoi (TOH), random number generation (RNG),
      operation span, and dual tasking. Confirmatory factor analysis indicated that the
      three target executive functions are moderately correlated with one another, but
      are clearly separable. Moreover, structural equation modeling suggested that the
      three functions contribute differentially to performance on complex executive
      tasks. Specifically, WCST performance was related most strongly to Shifting, TOH
      to Inhibition, RNG to Inhibition and Updating, and operation span to Updating.
      Dual task performance was not related to any of the three target functions. These
      results suggest that it is important to recognize both the unity and diversity of
      executive functions and that latent variable analysis is a useful approach to
      studying the organization and roles of executive functions.

PMID- 10945923
TI  - The ischemic heart--experimental models.
AB  - Results obtained by experimental studies of the ischemic heart have been of
      tremendous importance for the understanding of physiology, biochemistry and
      lately also the molecular genetics of the heart. Experimental models in use for
      the study of the ischemic heart involve studies on the integrated organism,
      experiments with isolated hearts or multicellular preparation, and also studies
      of cells isolated from the heart. Regional ischemia in the anaesthetized animal
      has been a standard model. Knowledge about infarct size limitation as well as
      heart function in acute and chronic ischemia has been obtained based on
      experiments in a wide variety of species. The isolated perfused heart has been
      subjected to extensive use. As a result, the understanding of intracellular
      processes is constantly developing. Cell models and transgenic-mice models
      represent promising additions. Each model and each species has certain advantages
      and disadvantages. Variability in susceptibility towards ischemia and reperfusion
      is also present. The consequences of ischemia can be described as contractile
      dysfunction and stunning, arrhythmia and infarction each representing different
      endpoints of injury. The experimental model is also heavily dependent on the
      endpoint that is chosen for the study. Results obtained in one experimental model
      can, therefore, not be generalized into universal conclusions about the ischemic
      heart. With respect to the human and the disease caused by myocardial ischemia,
      fragments of knowledge put together from different types of experimental models
      create the background for successful design of potential treatment.

PMID- 10945924
TI  - Stress modulates the enzymatic inducibility by benzo[alpha]pyrene in the rat
      liver.
AB  - The role of stress on the inducibility by benzo[alpha]pyrene (B[alpha]P), a
      representative polycyclic aromatic hydrocarbon, of several drug-metabolizing
      enzymes was investigated in rats, using restraint stress and mild unpredictable
      stress as models of psychological stress. Restraint stress was found to
      significantly suppress basal ethoxyresorufin 7-dealkylase (EROD) and
      pentoxyresorufin 7-dealkylase (PROD) activities (two-fold). In contrast, mild
      unpredictable stress markedly increased basal EROD activity, while PROD activity
      was not affected. In addition, both types of stress resulted in a significant
      reduction of basal p -nitrophenol hydroxylation (PNP). It is worth noting that
      restraint stress greatly enhanced the inducibility of EROD, methoxyresorufin 7
      dealkylase (MROD) and to a lesser extent PROD activities by B[alpha]P, while mild
      unpredictable stress had no, or only a mild effect on the inducibility of
      cytochrome P450s (CYPs) by B[alpha]P. In conclusion, psychological stress may
      modulate different enzymatic systems which are vital elements of the
      detoxification mechanisms of the body. The two distinct types of psychological
      stress used in this study appear to affect the enzymatic systems under
      investigation in a stress-specific manner at the basal level and at the induced
      state by B[alpha]P.

PMID- 10945925
TI  - Immobilization stress-induced changes in brain acetylcholinesterase activity and
      cognitive function in mice.
AB  - In the present study, the effect of acute and chronic immobilization stress on
      brain acetylcholinesterase (AChE) enzyme activity and cognitive function in mice
      was investigated. Mice were immobilized by strapping for 150 min. One group of
      mice were only immobilized once (acute stress) while in another group mice were
      immobilized (150 min) daily for 5 consecutive days (chronic stress). Specific
      AChE enzyme activity (micromol min(-1)mg(-1)) was estimated by a
      spectrophotometric method in the whole brain of mice subjected to acute and
      chronic stress. In the acute stress group, AChE activity (0.24922 +/- 0.011) in
      the detergent-soluble fraction was found to be significantly decreased in
      comparison to the control group (0.33561 +/- 0.022). Chronic stress did not cause
      any significant change in AChE activity in the detergent-soluble fraction. In the
      salt-soluble fraction, AChE activity was significantly decreased only in the
      chronic stress group (0.08791 +/- 0.011) as compared to the control group
      (0.12051 +/- 0.011). A passive avoidance test was used to assess cognitive
      function. The transfer latency time (TLT) from a light to dark chamber was
      recorded in the control and acute stress groups (30 min after immobilization is
      over) on day 1 (Trial I) and the following day (Trial II). The acute stress group
      showed an increase (178%) in TLT from Trial I to Trial II, which was
      significantly higher than that of the non-stress control group (75%). In the
      chronic stress group, Trial I was undertaken 30 min after the last
      immobilization, i.e. on day 5 and 24 hr later, Trial II. However, the chronically
      stressed mice showed an increase (70%) in TLT similar to the control group. Thus
      this study shows that acute immobilization stress may enhance cognitive function
      in mice which may be attributed to a decrease in AChE activity leading to an
      increase in cholinergic activity in the brain.

PMID- 10945926
TI  - Effect of DL-alpha-lipoic acid on neural antioxidants in aged rats.
AB  - The effect of DL-alpha-lipoic acid on lipid peroxidation and antioxidants were
      evaluated in various brain regions of young and aged rats. In aged rats, the
      levels of ascorbic acid, alpha-tocopherol and glutathione were low whereas the
      lipid peroxidation rate, as revealed by malonaldehyde content, was found to be
      high. Lipoic acid, an antioxidant, was administered intraperitoneally (100 mg/kg
      body weight/day) for 7 and 14 days. Lipoate-administered aged rats brought about
      reduction in lipid peroxidation and elevation in the levels of antioxidants. The
      modulatory effect of lipoate in decreasing age-associated alterations observed in
      our study proves its role as a potent antioxidant in the brain of aged rats.

PMID- 10945927
TI  - Effect of DL-alpha-lipoic acid on tissue nucleic acid contents in aged rats.
AB  - We have attempted to evaluate the effect of DL-alpha-lipoic acid on nucleic acid
      and protein contents in young and aged rats. An age-associated decrease in the
      deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein contents were
      observed in aged rats. DL-alpha-lipoic acid was administered intraperitoneally
      (100 mg/kg body weight/day) to young and aged rats from 7 and 14 days. Lipoate
      administration demonstrated a substantial increase in nucleic acid and protein
      contents in aged rats. Hence it can be justified that lipoate is functionally
      efficient in helping the cell to recover from oxidative damage.

PMID- 10945928
TI  - The effect of PK 11 195, a specific antagonist of the peripheral benzodiazepine
      receptors, on body weight in rats chronically exposed to diazepam.
AB  - This study was undertaken to evaluate the effect of acute and repeated (daily and
      weekly) intravenous (IV) administration of PK 11 195 (PK; 10 mg kg(-1)) on body
      weight (BW) in Sprague-Dawley male and female rats exposed for 4-8 weeks to
      diazepam (DZ) slowly released from Silastic capsules (120 and 90 mg/capsule/week
      for males and females, respectively). Rats implanted with empty capsules served
      as controls. Both acute and repeated (daily and weekly) administration of PK
      inhibited BW gain to a greater extent in male than in female rats that received
      identical treatment. There was no difference in PK effect between DZ-treated and
      control rats. Furthermore, regardless of treatment or gender, PK-induced
      inhibition of BW gain lessened during repeated administration of PK. The present
      data indicate that PK-induced inhibition of BW gain is related to gender rather
      than to chronic DZ treatment.

PMID- 10945929
TI  - The effect of baclofen on the locomotor activity of control and small-platform
      stressed mice.
AB  - The effect of baclofen on the locomotor activity of control and small-platform
      stressed mice was studied. In the small platform technique, mice are forced to
      stay on small platforms (d= 3.5 cm) surrounded by water for 24 h. Small platform
      stress increased the locomotor activity of mice in the actometer. Baclofen
      administered at doses of 0.25, 0.5 and 1.0 mg kg(-1)(i.p.) had no effect on the
      locomotor activity of control mice. In small-platform-stressed mice, the
      locomotor depressant effect of baclofen was pronounced, being statistically
      significant at a dose of 1.0 mg kg(-1). These data suggest that small platform
      stress induces hypersensitivity of mice to the motor depressant effect of
      baclofen. On the basis of these data it could be proposed that small platform
      stress induces changes in the function of GABA(B)receptors and that
      GABA(B)receptors participate in the behavioural changes caused by small platform
      stress.

PMID- 10945930
TI  - Behavioural activity of (S)-3,5-DHPG, a selective agonist of group I metabotropic
      glutamate receptors.
AB  - The influence of intracerebroventricular (i.c.v.) injections of (S)-3,5
      dihydroxyphenyl-glycine (S)-3,5-DHPG, a selective agonist of group I metabotropic
      glutamate receptors (mGluRs), on the activity of the central nervous system was
      examined in male rats. (S)-3,5-DHPG at doses of 25, 50 and 100 nmol significantly
      attenuated crossings of squares and rearings, but not bar approaches, in an 'open
      field' test and failed to change apomorphine-induced stereotypy. (S)-3,5-DHPG at
      the above doses, given immediately after the learning trial, significantly
      facilitated the consolidation process in a passive avoidance situation, but given
      before the learning trial and before the retention testing did not have any
      influence on acquisition and retrieval processes, respectively. Moreover, (S)-3,5
      DHPG did not influence recognition memory evaluated in an object recognition
      test. These results may suggest that activation of group I mGluRs takes part in
      the consolidation process in affectively-motivated memory, but is probably not
      necessary for processing of recognition memory, and that (S)-3,5-DHPG memory
      facilitation seems to be independent of glutamatergic and dopaminergic
      interaction.

PMID- 10945931
TI  - N-Methyl-D-aspartic acid- and metaphit-induced audiogenic seizures in rat model
      of seizures.
AB  - The effects of NMDA (N-methyl-D-aspartic acid) on metaphit (1-[1(3
      isothiocyanatophenyl)-cyclohexyl]piperidine)-induced audiogenic seizures in adult
      male Wistar albino rats were studied with the aim of developing a suitable animal
      model of seizures. The animals were divided into four experimental groups: 1,
      saline control; 2, metaphit-injected; 3, metaphit + NMDA administered and 4, NMDA
      treated. Upon the treatment, the rats were exposed to sound stimulation (100 +/-
      3 dB, for 60 s) at hourly intervals and the incidence and severity (running,
      clonus and tonus) of seizures were analysed. In group 3, only the animals which
      did not exhibit any metaphit-induced audiogenic seizures over 8 h were given a
      subconvulsive NMDA dose after the eighth audiogenic testing. For EEG recordings,
      three gold-plated screws were implanted into the rat skull. In most animals,
      metaphit led to EEG abnormalities and elicited epileptiform activity recorded as
      spikes, polyspikes and spike-wave complexes. Maximum incidence and severity of
      metaphit-induced convulsions occurred 8 h after injection (incidence 9/12),
      abating gradually until disappearing 30 h later. NMDA alone provoked no seizure
      response but the initial signs characterized by isolated spike activity evolving
      into sporadic slow-wave complexes, thus representing a proconvulsive brain state,
      were observed. This compound led to stereotyped behaviour seen as asymmetric
      posture, loss of righting reflex and tonic hind limb extension lasting for 60-90
      min. It also potentiated metaphit-induced audiogenic seizures. Potentiation of
      metaphit-related audiogenic seizures by NMDA was recorded in three out of 17 rats
      that had never displayed seizures in eight previous testings, with a maximum
      incidence of eight out of 17 animals, 13-14 h after metaphit administration and
      seizures lasted for 10 h.

PMID- 10945932
TI  - Saccharin effects on morphine-induced antinociception in the mouse formalin test.
AB  - This study was performed to investigate the role of sweetness and taste
      sensations of the non-caloric sweetener saccharin on pain and morphine
      antinociception by the formalin test in mice. The formalin test was chosen
      because it measures the response to a long-lasting nociceptive stimulus and thus
      may closely resemble clinical pain. The total time (seconds) spent licking and
      biting the injected paw (indices of nociception) during periods of 0-5 min (early
      phase) and 10-30 min (late phase) were measured as an indicator of pain and
      inflammatory responses. A 12 days pretreatment of animals with saccharin (0.04%,
      0.08%, 0.16%) produced complex effects on the action of morphine. All doses
      significantly potentiated the low dose (1.5 mgkg(-1)) of morphine-induced
      analgesia in the early phase significantly but antagonized the effect of morphine
      (3 mgkg(-1)). The effect of high doses of morphine (6-9 mgkg(-1)) was antagonized
      by the low dose of saccharin (0.04%), but the effect of morphine (6 mgkg(-1)) was
      potentiated with high concentrations of saccharin (0.08% and 0.16%). All doses of
      saccharin decreased the analgesic effect of morphine at a dose of 9 mgkg(-1).
      Analgesic effects of low doses of morphine (1.5-3 mgkg(-1)) were decreased by all
      doses of saccharin in the late phase. Different concentrations of saccharin also
      affected the antagonistic effect of naloxone (0.4 mgkg(-1)) on morphine-induced
      analgesia in both phases of the formalin test. The high dose of saccharin (0.16%)
      potentiated the effect of naloxone in the late phase. The results obtained
      suggest that sweet sensation is an important factor in mediating morphine
      analgesic properties. It is therefore inappropriate to use different
      concentrations of sweet saccharin solutions interchangeably.

PMID- 10945933
TI  - Cerebroprotective drugs shorten the hypoxia-induced onset of electrical silence
      in unanesthetized rats.
AB  - Pharmacological agents that delay the hypoxic arrest of neuronal electrical
      activity, as indicated by the suppression of electroencephalogram (EEG), have
      previously been thought to increase brain resistance to oxygen insufficiency. On
      the other hand, acceleration of the EEG suppression may offer some protection
      against severe hypoxia by reducing neuronal energy spending on electrogenesis. In
      unanesthetized rats we examined the effects of several antihypoxic drugs on the
      time of appearance of isoelectric EEG (tiEEG), caused by normobaric hypoxia. In
      addition, alterations in cerebral blood flow induced by hypoxia and by some drugs
      were monitored using polarographic techniques to determine if cerebrocirculatory
      changes play a significant role in the drug effects on tiEEG. We also assessed
      drug effects on behavioral recovery after hypoxia by measuring the latency of
      restoration of the head-withdrawal reflex upon vibrissae stimulation.
      Pentobarbital (30 and 60 mgkg(-1)i.p.), chloralhydrate (400 mgkg(-1)i.p.)
      flunarizine (50-100 mgkg(-1)p.o.), hydergine (3-50 mgkg(-1)p.o.), nicergoline (50
      mgkg(-1)and 85 mgkg(-1)p.o.), sabeluzole (3 and 7.5 mgkg(-1)i.p.) and vincamine
      (80 mgkg(-1)p.o.) reduced tiEEG (mean 27.1 +/- 3.3 min prior to drugs). In
      contrast, idebenone (29-85 mgkg(-1)p.o.) and vinpocetine (29-85 mgkg(-1)p.o.) had
      no significant effects on tiEEG. The divergent effects on cerebral blood flow
      suggest an insignificant role for cerebrocirculatory changes in the drug-induced
      reduction of tiEEG during severe hypoxia. The drug effects on recovery of the
      head-withdrawal reflex (mean 4.2 +/- 1.3 min prior to drugs) varied from a delay
      (sabeluzole) to acceleration (flunarizine) with no correlation to the effects on
      tiEEG, suggesting that EEG criteria alone may not predict the course of
      functional recovery.

PMID- 10945934
TI  - Sensitization to the morphine-like discriminative stimulus effects of
      buprenorphine in rats.
AB  - An experiment was performed to determine whether chronic non-contingent
      administration of morphine would produce cross-sensitization to the cueing
      properties of buprenorphine or D-amphetamine. To this end the sensitivity to the
      discriminative stimulus effects of morphine, buprenorphine and D-amphetamine was
      determined in rats trained to discriminate 10 mg kg(-1)morphine from saline in a
      food-reinforced operant task. Seven rats were given repeated non-contingent
      treatments with morphine (20 mg kg(-1)on saline or no-test days and 10 mg kg(
      1)on drug days) starting 20 days before the beginning of discrimination training;
      another six animals received injections of saline. Chronic administration of
      morphine resulted in sensitization to the discriminative stimulus effect of this
      drug and in cross-sensitization to the discriminative stimulus effect of
      buprenorphine. D-Amphetamine produced only saline lever selection in all rats. In
      conclusion, the present results confirm that the stimulus properties of opioid
      drugs may be enhanced, rather than decreased, in animals with a history of
      repeated non-contingent treatment with morphine. Sensitization to central-acting
      drugs is thought to play a role in the psychopathology of drug abuse. Hence, the
      present results point out the necessity of considering the effects of drugs which
      show tolerance, and those which show sensitization, under any particular drug
      regimen.

PMID- 10945935
TI  - Effects of nitric oxide synthesis inhibition on the atrial natriuretic peptide
      system.
AB  - The present study was aimed at investigating whether nitric oxide (NO) has a
      modulatory effect on the atrial natriuretic peptide (ANP) system. The atrial
      tissue expression of ANP mRNA was determined in rats treated with an inhibitor of
      NO synthesis, N(G)-nitro-L-arginine methyl ester (L-NAME), for 4 weeks.
      Measurements of ANP peptides and NO metabolites in the plasma and atria were also
      taken. The blood pressure was increased by the treatment with L-NAME (40 mg l(
      1)drinking water). The atrial expression of ANP mRNA was increased. Atrial
      natriuretic peptides were also increased, while NO metabolites decreased in the
      plasma and atrial tissue. An antihypertensive treatment with losartan reversed
      the blood pressure to the control level. However, the atrial expression of ANP
      mRNA was not affected but remained at an increased level. Accordingly, the plasma
      ANP was elevated and NO decreased. Supplementation with L-arginine, the substrate
      to NO synthase, prevented the changes induced by L-NAME. These results suggest
      that the synthesis and release of ANP be regulated by local release of NO with a
      transcriptional inhibition.

PMID- 10945936
TI  - Influence of retrieval conditions on renal medulla injury: evaluation by proton
      NMR spectroscopy in an isolated perfused pig kidney model.
AB  - BACKGROUND: Delayed graft function (DGF) has remained an important complication
      after renal transplantation. The exact causes of DGF remain to be clarified,
      particularly the impact of retrieval conditions and preservation factors. In the
      present investigation, (1)HNMR spectroscopy of urine was assessed in order to
      detect the influence of retrieval condition on renal medulla damage. METHODS: The
      isolated perfused pig kidney (IPK) was used to assess initial renal function from
      multiorgan donors (MOD) or single organ donors (SOD) after in situ cold flush and
      24-h cold storage (CS) preservation with two standard preservation solutions:
      Euro-Collins (EC) and University of Wisconsin (UW) solutions. Kidneys flushed
      with cold heparinized saline and immediately perfused were used as the control
      group. Kidneys were perfused for 90 min at 37.5 degrees C for functional
      evaluation. During reperfusion, renal perfusion flow rate (PF) was measured.
      Glomerular filtration rate (GFR), tubular reabsorption of Na(+), and lactate
      dehydrogenase (LDH) and N-acetyl-beta-d-glucosaminidase (NAG) excretions were
      determined. Ischemia-reperfusion impairment was also determined by histological
      techniques and (1)HNMR spectroscopy. RESULTS: PF, GFR, and tubular reabsorption
      of Na(+) were significantly decreased in experimental groups when compared to the
      control group but there was no significant difference between experimental SOD
      groups. GFR was significantly greater in UW-MOD than in EC-MOD and tubular
      reabsorption of Na(+) was significantly greater in UW-MOD than in EC-MOD after 45
      min of reperfusion. The release of LDH in the effluent and the urinary excretion
      of NAG were not significantly different after 24-h CS in the various experimental
      groups. The most relevant resonances determined by (1)HNMR spectroscopy were
      citrate, trimethylamine-N-oxide, lactate, acetate, and amino acids. Excretion of
      these markers was significantly different when compared to biochemical markers. A
      resonance (P) detected particularly in EC-MOD after 24-h CS was identified and
      well correlated to renal dysfunction. Histological study showed that
      ultrastructural damage and mitochondrial injury were more pronounced in the EC
      MOD group. CONCLUSION: These results show that retrieval condition influences
      renal medullary damage. NMR spectroscopy, which is a noninvasive and
      nondestructive technique, is more efficient in assessing renal damage than
      conventional histology and biochemical analysis.

PMID- 10945937
TI  - Influence of amrinone on tissue oxygenation of jejunal mucosa during endotoxemia.
AB  - BACKGROUND: The intestinal mucosa is the portion of the gut most susceptible to
      impaired perfusion and oxygen delivery. The phosphodiesterase (PDE) inhibitor
      amrinone has been proposed to improve oxygen delivery and tissue perfusion during
      sepsis. The objective of this study was to investigate the effects of amrinone on
      arterial oxygenation (Pao(2)) and tissue oxygenation (Ptio(2)) of jejunal mucosa
      during endotoxemia. MATERIALS AND METHODS: Forty anesthetized and ventilated rats
      were laparotomized and a jejunal portion was exteriorized and fixed on a
      plexiglass stage. The jejunum was punctured and a Clark-type microcatheter Po(2)
      probe and a microthermocouple were placed on the mucosa to measure Ptio(2). The
      animals were randomly assigned to receive one of the four treatments: infusion of
      Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without amrinone
      pretreatment (LPS group); infusion of LPS with amrinone pretreatment (40
      microg/kg/min, start 30 min before LPS infusion, amrinone + LPS group); no
      treatment with either amrinone or LPS (control group); treatment with amrinone
      without LPS infusion (amrinone group). Mean arterial pressure (MAP), heart rate
      (HR), Pao(2), and Ptio(2) were measured 30 min before and 0, 60, and 120 min
      after induction of endotoxemia. RESULTS: MAP remained stable in the control and
      LPS groups. In the amrinone + LPS group MAP decreased within the first 30 min of
      amrinone infusion and decreased further during endotoxemia. Pao(2) remained
      stable in the control group and decreased in the LPS group. This endotoxin
      induced decrease in Pao(2) was attenuated in the amrinone + LPS group. The
      mucosal Ptio(2) decreased in the LPS group but remained stable in both the
      control and amrinone + LPS groups. CONCLUSIONS: Pretreatment with amrinone was
      able to diminish a decrease in Pao(2) during endotoxemia, indicating that
      pulmonary dysfunction was attenuated. Endotoxin-induced tissue hypoxia of the
      intestinal mucosa, however, could be fully prevented, indicating that an
      additional improvement in compromised tissue perfusion had occurred.

PMID- 10945938
TI  - Patterns of failure at the instrument-tissue interface.
AB  - BACKGROUND: The effect of jaw design on grip security and tissue trauma is poorly
      understood. This project establishes an in vitro model of the instrument-tissue
      interface. MATERIALS AND METHODS: Aluminum jaws with teeth of differing size and
      shape gripped fresh sheep stomach with variable apposing (squeeze) pressure. The
      tissue was extracted at a rate of 50 mm/min until either the grip or the tissue
      failed. The load at which the grip failed, the maximum (peak) load generated, and
      the mode of failure were noted. The data were analyzed using ANOVA and a post hoc
      Duncan's multiple range test when appropriate. RESULTS: Increasing the apposing
      pressure increased grip security. Grip security of 1- and 2-mm pitch teeth were
      significantly greater than for plane jaws and smaller-pitch teeth (P < 0.001). Of
      the wave pattern jaws, 2-mm pitch waves also had significantly greater grip
      security than plane jaws and smaller pitch waves (P < 0.01). Wave pattern jaws
      produced significantly less tissue trauma than teeth (P < 0.0001). CONCLUSIONS:
      Increasing the size of instrument teeth increases grip security but at the
      expense of tissue trauma. Wave pattern jaws result in significantly less tissue
      trauma than teeth. This model measures grip security precisely and allows for
      comparison between jaws of different patterns.

PMID- 10945939
TI  - Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats.
AB  - BACKGROUND: Recently, eicosapentaenoic acid (EPA) was found to have an anti
      inflammatory effect attributable to diminished synthesis of arachidonic acid
      metabolites that initiate acute lung injury. We evaluated the ability of dietary
      EPA supplementation to prevent endotoxin-induced acute lung injury in rats.
      MATERIALS AND METHODS: Rats fed a standard diet were divided randomly into two
      groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl
      ester emulsion (EPA rats), while in the other group the diet was supplemented
      with vehicle alone (control rats). Fatty acid components of alveolar macrophages
      (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM
      exposed in vitro to calcium ionophore A23187. Plasma concentrations of
      thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after
      inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight
      ratios were calculated for the lungs to assess pulmonary edema, and neutrophils
      were counted in pulmonary parenchyma and peripheral blood. RESULTS: Arachidonic
      acid content and LTB(4) generation in AM were significantly lower in EPA rats
      than in controls; conversely, EPA content and LTB(5) generation in AM were
      significantly higher in the EPA group. Neutrophil counts in lung parenchyma and
      peripheral blood did not differ between groups, but W/D and plasma TxB(2)
      concentrations were significantly lower in EPA rats. CONCLUSIONS: EPA
      supplementation depressed arachidonic acid content and LTB(4) generation in AM
      and plasma TxB(2) in our model, leading to decreased pulmonary edema.

PMID- 10945940
TI  - Graft vasculopathy and tolerance: does the balance of Th cells contribute to
      graft vasculopathy?
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is sometimes observed even
      though the allograft may survive indefinitely. In this study, we examined whether
      or not the preferential activation of Th2-type cells prevents the development of
      CAV. METHODS: Hearts from C57BL/10 mice were transplanted heterotopically into
      the abdominal cavities of C3H.He recipient mice, and monoclonal antibodies (mAbs)
      to T-cell receptor (TCR) alphabeta or CD80/CD86 were administered after
      transplantation. The incidence of CAV was then examined histologically. To
      investigate the relative Th1/Th2 balance, the levels of IFNgamma and IL4 in the
      transplanted hearts were measured. RESULTS: Indefinite heart graft survival was
      observed in mice treated with either the anti-TCRalphabeta or anti-CD80/CD86 mAbs
      and these mice accepted donor-type (C57BL/10) skin grafts but rejected those from
      a third party (BALB/c). Evidence of CAV was found in the mice treated with the
      anti-TCRalphabeta mAb, but CAV did not develop in the mice treated with anti
      CD80/CD86 mAbs. Preferential activation of Th2-type cells was dominant in the
      tolerant mice treated with anti-TCRalphabeta mAb, but it was not dominant in the
      tolerant mice treated with anti-CD80/CD86 mAbs. CONCLUSION: These findings
      suggest that the dominance of Th2-type cells does not prevent allograft
      vasculopathy.

PMID- 10945941
TI  - NFkappaB expression during cold ischemia correlates with postreperfusion graft
      function.
AB  - In liver transplantation, activation of NFkappaB occurs upon reperfusion, yet few
      data exist regarding NFkappaB activation during cold ischemia. We hypothesized
      that activation of NFkappaB may initially occur during cold ischemia, prior to
      reperfusion, and serve as an important determinant of postreperfusion function.
      To test this hypothesis, serial biopsies during porcine liver harvest were
      obtained immediately upon laparotomy, upon completion of dissection, after 45 and
      120 min of cold ischemia, and 60 and 180 min after reperfusion. Nuclear extracts
      were isolated for Western blot analysis of NFkappaB. Hepatic function was
      assessed through bile output and sorbitol dehydrogenase (SDH) activity. NFkappaB
      expression was maximal at 45 min of cold ischemia and decreased by 120 min. The
      expression at 120 min of cold ischemia correlated with markers of postreperfusion
      function, namely bile flow and SDH activity. During reperfusion a second distinct
      peak occurred at 180 min. Increased expression of NFkappaB at 180 min of
      reperfusion correlated directly with prior expression at 120 min during cold
      ischemia and with increased SDH activity. These data indicate that nuclear
      expression of NFkappaB demonstrate two distinct peaks of activity, one during
      cold ischemia and one after reperfusion. Enhanced expression of NFkappaB during
      cold ischemia not only correlates directly with NFkappaB expression during
      reperfusion, but also correlates inversely with postreperfusion graft function.

PMID- 10945942
TI  - Bioactive interleukin-8 is expressed in wounds and enhances wound healing.
AB  - BACKGROUND: Wound healing is a sequential biological process that involves the
      integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes,
      and remodeling of the scar, all of which are regulated by specific soluble
      mediators. To modulate wound healing specific mediators have to be identified and
      functionally characterized. Therefore we addressed this study on the
      polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its
      function in epidermal wound healing. MATERIALS AND METHODS: Peptide purification,
      bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on
      human wound fluid from burn blisters and skin graft donor sites. Histology for IL
      8 immunoreactivity was included. In vitro human keratinocytes were assayed for
      proliferation, migration, and integrin expression after IL-8 treatment. Wounding
      experiments with topical IL-8 were performed in a chimeric mouse model. RESULTS:
      IL-8 was found to be the major bioactive chemoattractant for PMNs in human
      blister and skin graft donor site wound fluids (mean levels ranging from 173
      ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular
      epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate
      source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue
      form as a second source of IL-8 possibly PMN derived. In vitro experiments on the
      effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a
      rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an
      increase in cells in S phase and overexpression of the integrin subunit alpha6.
      In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric
      mouse model enhanced reepithelialization in IL-8 treated animals over controls
      due to elevated numbers of mitotic keratinocytes. Wound contraction was
      significantly diminished by topical IL-8. CONCLUSIONS: These results indicate the
      sequential function of endogenous IL-8 in all phases of human wound healing.
      Topical IL-8 may be useful in impaired wound healing.

PMID- 10945943
TI  - Electrochemical lesions in the rat liver support its potential for treatment of
      liver tumors.
AB  - BACKGROUND: An effective therapy is needed for patients with surgically
      unresectable liver tumors who have very limited life expectancy. One possible
      treatment is electrochemical tumor necrosis. This study investigated the natural
      history of electrochemical lesions in the normal rat liver. MATERIALS AND
      METHODS: A direct current generator, connected to platinum electrodes, was used
      to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2
      weeks, 2 months, and 6 months after treatment and the macroscopic and
      histological appearance of the necrotic lesions was followed. RESULTS: No animal
      died as a result of electrolysis; postoperatively, all gained weight normally.
      Liver enzymes were significantly (P < 0.001) elevated after treatment, but
      returned to normal after a week. Two days after electrolysis, histology confirmed
      an ellipsoidal area of coagulative necrosis at the site of the electrode tip and
      commonly a segment of peripheral necrosis. After 2 weeks there was histological
      evidence of healing. By 6 months, very little necrotic tissue remained within a
      small fibrous scar. CONCLUSIONS: Electrolysis is a safe method for creating
      defined areas of liver necrosis that heal well with no associated mortality. This
      study supports the potential of electrolysis for treating patients with
      unresectable liver tumors.

PMID- 10945944
TI  - Viral infection abrogates CD8(+) T-cell deletion induced by costimulation
      blockade.
AB  - BACKGROUND: Treatment with a single donor-specific transfusion (DST) plus a brief
      course of anti-CD154 monoclonal antibody (mAb) prolongs skin allograft survival
      in mice. It is known that prolongation of allograft survival by this method
      depends in part on deletion of alloreactive CD8(+) T cells at the time of
      tolerance induction. Recent data suggest that infection with lymphocytic
      choriomeningitis virus (LCMV) abrogates the ability of this protocol to prolong
      graft survival. METHODS: To study the mechanism by which viral infection
      abrogates allograft survival, we determined (1) the fate of tracer populations of
      alloreactive transgenic CD8(+) T cells and (2) the duration of skin allograft
      survival following treatment with DST and anti-CD154 mAb in the presence or
      absence of LCMV infection. RESULTS: We confirmed that treatment of uninfected
      mice with DST and anti-CD154 mAb leads to the deletion of alloreactive CD8(+) T
      cells and is associated with prolongation of skin allograft survival. In
      contrast, treatment with DST and anti-CD154 mAb in the presence of intercurrent
      LCMV infection was associated with the failure to delete alloreactive CD8(+) T
      cells and with the rapid rejection of skin allografts. The number of alloreactive
      CD8(+) cells actually increased significantly, and the cells acquired an
      activated phenotype. CONCLUSIONS: Interference with the deletion of alloreactive
      CD8(+) T cells mediated by DST and anti-CD154 mAb may in part be the mechanism by
      which viral infection abrogates transplantation tolerance induction.

PMID- 10945945
TI  - Videoendoscopic thoracic aorta-to-femoral artery bypass in the pig.
AB  - BACKGROUND: The thoracoscopic approach to the aorta has the advantages of easy
      aortic dissection, excellent inflow, improved exposure in the thorax without
      insufflation, and ability to employ both laparoscopic and traditional
      instruments. Our aim was to develop a thoracoscopic technique for descending
      thoracic aorta-to-femoral artery bypass (TAFB) in the pig that results in
      acceptable short-term survival and graft patency. MATERIALS AND METHODS:
      Thoracoscopic TAFB was performed in 11 pigs. Using two-lung ventilation, the
      animals were placed in a 45 degrees left lateral semidecubitus position. A fan
      lung retractor, two dissecting ports, intercostal artery loops, and camera were
      placed through five 10- to 20-mm thoracoscopic incisions. After aortic
      dissection, an 8-mm graft was passed through a retroperitoneal tunnel. Rumel
      tourniquets were used for aortic occlusion after placement of a shunt. End-to
      side endoscopic anastomosis was completed with knots tied extracorporeally. The
      left femoral anastomosis was completed under direct vision. Duplex ultrasound of
      the graft was done on postoperative days 1, 3, and 7. RESULTS: Thoracoscopic TAFB
      was completed in all animals. Mean aortic anastomosis time was 57 min (range, 34
      145); and mean cross-clamp time, 74 min (range, 53-155). Mean operative time was
      310 min; the first six operations lasted longer than the last five (338 min vs
      276 min, P < 0.04). Average blood loss was 611 ml (range, 250-1300). Two animals
      died due to anesthetic complications. One (11%) of the nine surviving pigs died
      on day 2 due to bleeding. Complications were paraplegia in one (11%) and graft
      thrombosis in another (11%). CONCLUSIONS: Videoendoscopic TAFB can be completed
      in pigs with acceptable short-term patency and survival. Further experience in
      thoracoscopic techniques can make TAFB a feasible and low-risk option for
      selected patients with aortoiliac occlusive disease.

PMID- 10945946
TI  - Lazaroid and pentoxifylline suppress sepsis-induced increases in renal vascular
      resistance via altered arachidonic acid metabolism.
AB  - Early sepsis leads to renal hypoperfusion, despite a hyperdynamic systemic
      circulation. It is thought that failure of local control of the renal
      microcirculation leads to hypoperfusion and organ dysfunction. Of the many
      mediators implicated in the pathogenesis of microvascular vasoconstriction,
      arachidonic acid metabolites are thought to be important. Vasoconstriction may be
      due to excess production of vasoconstrictors or loss of vasodilators. Using the
      isolated perfused kidney model, we describe a sepsis-induced rise in renal
      vascular resistance and increased production of key arachidonic acid metabolites,
      both vasoconstrictors and vasodilators, suggesting excessive production of
      vasoconstrictors as a cause for microcirculatory hypoperfusion. There is evidence
      of increased enzymatic production of arachidonic acid metabolites as well as
      nonenzymatic, free radical, catalyzed conversion of arachidonic acid.
      Pentoxifylline (a phosphodiesterase inhibitor) and U74389G (an antioxidant) both
      have a protective effect on the renal microcirculation during sepsis. Both drugs
      appear to alter the renal microvascular response to sepsis by altering renal
      arachidonic acid metabolism. This study demonstrates that sepsis leads to
      increased renal vascular resistance. This response is in part mediated by
      metabolites produced by metabolism of arachidonic acid within the kidney. The
      ability of drugs to modulate arachidonic acid metabolism and so alter the renal
      response to sepsis suggests a possible role for these agents in protecting the
      renal microcirculation during sepsis.

PMID- 10945947
TI  - Inhibitory effect of TNP-470 on hepatic metastasis of mouse neuroblastoma.
AB  - PURPOSE: TNP-470 is a strong inhibitor of angiogenesis. The present study was
      designed to determine whether the angiogenesis inhibitor TNP-470 inhibits
      metastasis of mouse neuroblastoma cells to the liver and thus increases survival.
      METHODS: A murine neuroblastoma cell line, C1300, and A/J mice were used in this
      study. First, to demonstrate the inhibitory effects of TNP-470 on angiogenesis,
      we quantified the area of angiogenesis on images made with SP-500 image analyzer
      (Olympus) 7 days after implanting a millipore chamber and compared the areas for
      the TNP-470-treated mice and control mice. Next, to determine the inhibitory
      effect of TNP-470 on metastasis of neuroblastoma cells to the liver, we made a
      murine hepatic metastasis model by implanting C1300 cells (1 x 10(6)) in the
      spleen of the mice and compared histologic findings, sizes, and weights of the
      livers of treated mice and control mice 14 days after the beginning of a 7-day
      infusion of TNP-470 (60 mg/kg). We also compared survival rates using the Kaplan
      Meier method. RESULTS: When the angiogenesis inhibitor TNP-470 was infused into
      mice that received tumor cells, the area of angiogenesis in the TNP-470-treated
      mice was smaller than that in the control mice (52.5 +/- 6.3 SD vs 94.1 +/- 27.6
      mm(2), P < 0.001). After the same treatment in other mice, no histologic evidence
      of metastasis was found, whereas control mice had countless tumor cell masses.
      Similarly, the weight of the liver was less in TNP-470-treated mice (0.8 +/- 0.1
      g vs 4.5 +/- 0.3 g, P < 0.001). Survival was longer in the TNP-470-treated mice
      than in controls (80% of treated mice were alive more than 60 days after
      treatment, whereas all control mice died by Day 20). CONCLUSION: TNP-470 inhibits
      metastasis of mouse C1300 neuroblastoma cells to the liver, and thus increases
      survival. TNP-470 inhibits metastasis by inhibiting angiogenesis.

PMID- 10945948
TI  - Dynamics of tissue neutrophil sequestration after cutaneous burns in rats.
AB  - BACKGROUND: Neutrophil recruitment in organs after burns may cause local vascular
      damage, which can be reduced by agents blocking neutrophil adhesion to the
      vascular wall. Because these agents may increase susceptibility to infection, it
      is important to characterize the dynamics of neutrophil sequestration in order to
      optimize an eventual anti-adhesion therapy. MATERIALS AND METHODS: Rats were
      scald burned over 20 or 40% of their total body surface area (TBSA) and saline
      resuscitated. Sham controls were used. Myeloperoxidase (MPO) activity was
      measured in lungs, liver, kidney, gut, and burned skin up to 1 week postburn.
      Extravascular accumulation of (125)I-labeled bovine serum albumin ((125)I-BSA)
      was measured at 12 h postburn. RESULTS: MPO activity in lungs, liver, and kidney
      was increased within 3 h postburn and returned to normal within 24-48 h. Peak MPO
      levels occurred at 6-12 h postburn and were similar for both burn sizes. No MPO
      increase was observed in gut. MPO levels in burned skin did not increase before 6
      h, peaked at 24 h, decreased at 48 h, but remained elevated for up to 7 days.
      Neutrophil recruitment in lungs and liver was confirmed histochemically. No
      neutrophils were found in kidneys. Extravascular (125)I-BSA was increased in
      lungs, liver, kidneys, and gut, in the 40% TBSA group only. CONCLUSIONS:
      Neutrophil sequestration in remote organs is a transient phenomenon while
      neutrophil homing into the wound site is sustained. Neutrophil accumulation
      dynamics are independent of burn size, although a minimum size is required to
      trigger vascular damage. Temporary early anti-adhesion therapy to reduce lung and
      liver neutrophil sequestration with little impact on neutrophil homing into the
      burn wound may be possible.

PMID- 10945949
TI  - Cervical heterotopic arterialized liver transplantation in the mouse.
AB  - BACKGROUND: Orthotopic liver transplantation in the mouse is an extremely
      demanding procedure. Since the mouse, however, would be a good model for the
      study of various transplantation-related problems, we designed a new surgical
      technique for cervical heterotopic arterialized reduced-size liver
      transplantation. METHODS: Eighty percent hepatectomy was performed ex vivo and
      the remaining liver segment was transplanted to the neck of the recipient. The
      donor aorta was anastomosed to the right common carotid artery, the portal vein
      to the distal right external jugular vein, and the donor suprahepatic vena cava
      to the proximal right external jugular vein using a cuff technique. The bile duct
      was brought out as a cutaneous stoma. RESULTS: This relatively simple technique
      was performed in 22 BALB/C mice and associated with a high success rate: three
      mice died within 5 days due to surgical complications. All grafts in survivors
      were structurally normal until postoperative day 7 and began to show histological
      signs of atrophy around day 14. CONCLUSIONS: It is concluded that this technique
      may be useful for preservation, regeneration and reperfusion studies, and factors
      responsible for the maintenance of hepatocyte integrity in heterotopic liver
      transplantation.

PMID- 10945950
TI  - Prolongation of rat islet xenograft survival in the liver of IFN-gamma-deficient
      mice.
AB  - The cellular mechanisms involved in islet xenograft rejection remain
      undetermined. In the present study, the role of interferon-gamma (IFN-gamma) in
      rat islet xenograft rejection was examined with the use of IFN-gamma-deficient
      mice as recipients and the results were compared with allografts. There was no
      significant difference in the survival of intrahepatic islet allografts in IFN
      gamma-deficient mice compared with that in wild-type mice. In contrast, a marked
      prolongation of rat islet xenograft survival was obtained in IFN-gamma-deficient
      mice without immunosuppression when compared with the survival in wild-type mice.
      In order to dissect the difference, infiltrating cells in the liver in
      association with rejection were examined with flow cytometry. An expansion of CD8
      T cells was seen in the liver of wild-type mice rejecting xenografts compared
      with isografts. There was no significant change in other cell populations. In IFN
      gamma-deficient mice, the expansion of CD8 T cells was seen in the liver
      rejecting xenografts; however, the time of development was markedly delayed by
      the time of rejection. These findings suggest that the acute rejection of rat
      islet xenografts in mice is IFN-gamma-dependent although the exact mechanisms
      remain unknown.

PMID- 10945951
TI  - Suppression subtractive hybridization to identify gene expressions in variant and
      classic small cell lung cancer cell lines.
AB  - Small Cell Lung Cancer (SCLC), a clinically aggressive cancer, accounts for
      approximately 25% of primary lung cancers. We carried out suppression subtractive
      hybridization (SSH), a PCR-based method for cDNA subtraction, between the human
      classic, NCI-H69 and variant, more aggressive NCI-N417 SCLC cell lines to isolate
      and characterize variable expression of genes, which may be responsible for
      differential degree of tumorigenicity of SCLC. Using NCI-N417 as a tester, we
      obtained 28 differentially expressed cDNA clones from a total of 60 arbitrarily
      picked clones. Among the 28 cDNA clones, 4 were unknown genes, 2 were fatty acid
      binding protein (FABP) with specific identification of mRNA for mammary-derived
      growth inhibitor (MDGI), 1 was human alpha-enolase, 4 were ribosomal proteins, 2
      were structural genes, vimentin and moesin (membrane-organizing extension spike
      protein), and 9 were homologous with murine leukemia viruses, whereas 2 others
      had enhanced expression in NCI-H69 and A549 cell lines, and 4 were cell surface
      proteins and murine type C retrovirus. Expression of FABP/MDGI was significantly
      high in NCI-H417, which may influence mitosis and cell growth as implicated in
      other tissues, contrary to the conclusion drawn for the role of MDGI in human
      breast cancer. Higher expression of ribosomal proteins in NCI-N417 compared to
      NCI-H69 may have a role in differential tumorigenicity and metastatic ability.
      Further, we obtained 14 differentially expressed cDNA clones by reversing the
      tester and driver, using NCI-H69 as a tester. Of these 14 differential cDNAs, 5
      were unknown genes, 2 were specific for keratins, others had similarities with
      protease inhibitor, human BAC clone, Alu RNA binding protein, and tumor
      expression-enhanced gene. Characterization of these differentially expressed cDNA
      clones will provide useful information in understanding of the genes responsible
      for differential tumorigenicity of SCLC.

PMID- 10945952
TI  - Insulin suppresses the increased activities of lysosomal cathepsins and ubiquitin
      conjugation system in burn-injured rats.
AB  - BACKGROUND: Burn injury results in increased rate of skeletal muscle protein
      degradation. In vitro studies on incubated muscles indicate that increased rate
      of protein degradation is due to activation of multiple proteolytic systems, but
      the supporting evidence is of an indirect nature. The present study was carried
      out to investigate the role of various lysosomal cathepsins, ubiquitin
      conjugation, and proteasome systems in accelerated proteolysis, and the effect of
      insulin in burn-induced muscle wasting syndrome. MATERIALS AND METHODS: Fifteen
      to twenty percent total body surface area scald burn injury was inflicted on the
      shaved dorsum of young growing rats. Insulin-treated rats received a daily single
      subcutaneous injection for 3 days (0.25-1.0 U/day). The rate of ubiquitin
      conjugation to endogenous proteins and exogenously added (125)I-lysozyme and the
      activities of various proteases were measured in muscle homogenates. RESULTS:
      Burn injury resulted in increased rate of ubiquitin conjugation to endogenous
      proteins and (125)I-lysozyme. Activities of cathepsins B, C, H, and L were also
      up-regulated following burn injury. When the burn-injured rats were treated with
      insulin, the increased rate of ubiquitin conjugation and cathepsin activities
      were suppressed to the control levels. CONCLUSIONS: The increased ubiquitin
      conjugation and lysosomal cathepsins contribute to accelerated protein
      degradation in burn-injured rats and insulin suppresses the muscle protein
      degradation at least in part by suppressing the activities of lysosomal
      cathepsins and of ubiquitin conjugation system.

PMID- 10945953
TI  - Deletion of endothelial nitric oxide synthase exacerbates myocardial stunning in
      an isolated mouse heart model.
AB  - BACKGROUND: While endothelial nitric oxide synthase (eNOS) is an important
      regulator of vascular tone, it is also constitutively expressed in cardiac
      myocytes and contributes to the regulation of myocardial function. The role of
      eNOS in ischemia-reperfusion is uncertain, however, with some studies showing
      beneficial effects while other studies demonstrate increased cardiac injury. We
      hypothesized that the beneficial effects of eNOS would predominate, and thus that
      targeted deletion of eNOS would exacerbate myocardial dysfunction following
      ischemia-reperfusion. MATERIALS AND METHODS: ENOS knockout and wild-type mouse
      hearts were Langendorff-perfused using Krebs bicarbonate buffer and subjected to
      20 min of global normothermic ischemia followed by 30 min of reperfusion.
      Myocardial function was measured using a ventricular balloon to determine time to
      onset of contracture, left ventricular developed pressure (LVDP), left
      ventricular end-diastolic pressure (LVEDP), and rate-pressure product (RPP).
      RESUKTS: Heart rate and coronary resistance were similar in both groups during
      baseline and reperfusion periods. Diastolic function as determined by peak LVEDP
      during ischemia and final LVEDP after reperfusion were worse in the eNOS knockout
      group vs wild-type (114 and 31 mmHg vs 92 and 18 mmHg, P <.05). Although RPP
      (heart rate x LVDP), measured as an index of systolic function, was initially
      better in eNOS knockouts (24216 vs 16353), wild-type hearts recovered more
      function than did eNOS knockout hearts by the end of 30 min of reperfusion (30892
      vs 20522, P <.05). CONCLUSIONS: These data suggest that the deletion of eNOS
      results in increased myocardial dysfunction following ischemia-reperfusion in an
      isolated heart model.

PMID- 10945954
TI  - Laparoscopic suturing evaluation among surgical residents.
AB  - BACKGROUND: Laparoscopic suturing is an integral part of advanced laparoscopic
      surgery training. The objective of this study was to evaluate the performance and
      preference of surgical residents performing intracorporeal and extracorporeal
      knot-tying techniques using conventional and Endo Stitch instruments. The
      residents were also evaluated on their suturing techniques using conventional
      instruments, the Endo Stitch, and the Suture Assistant. METHODS: Using an
      inanimate laparoscopic trainer model, 39 residents were evaluated as they
      performed laparoscopic knot tying exercises. Endpoints of the study were
      execution time and subjective preference of surgical residents with respect to
      the type of instrument used for knot tying. Forty-three residents were evaluated
      as they performed laparoscopic suturing exercises with three different types of
      suturing instruments using the same endpoints. RESULTS: The intracorporeal
      technique was the preferred (89%) method of knot tying among surgical residents.
      The time for completion of laparoscopic suturing was significantly (P < 0.05)
      shorter with the Endo Stitch (114 +/- 64 s) than with the conventional instrument
      (206 +/- 107 s) or the Suture Assistant (151 +/- 70 s). Residents preferred the
      use of the Endo Stitch in all three categories for suturing, knot tying, and
      handling. CONCLUSION: The Endo Stitch enhanced laparoscopic skills and was the
      preferred instrument for laparoscopic knot tying and suturing among surgical
      residents.

PMID- 10945955
TI  - Hypericin and photodynamic therapy decreases human pancreatic cancer in vitro and
      in vivo.
AB  - BACKGROUND: The treatment of pancreatic cancer has remained dismal despite
      advances in medical and surgical care. Recent preclinical data have revealed that
      hypericin, a photochemical dye, is activated by green light and generates toxic
      radical species in tumors. We hypothesized that interstitial hypericin and laser
      phototherapy would decrease pancreatic cancer growth. METHODS: MiaPaCa-2 and PANC
      1 cells were grown in tissue culture. In vitro experiments were performed with
      addition of 10 microg of hypericin/500,000 cancer cells. Cells were incubated
      with hypericin for 2 h. Cells were then exposed to KTP532 green laser light for 1
      min at 0.6 W using a cylindrical diffuser tip. Cell growth was measured by MTT
      assay 24 h after laser treatment, N = 12. MiaPaCa-2 cells were implanted
      subcutaneously and orthotopically in pancreas of nude mice. After 5 weeks, both
      tumors were injected with 100 microg of hypericin followed by insertion of a
      cylindrical diffuser tip into the tumor center. Mice received 200J KTP laser
      light at 1.0 W in two sites. Tumors were measured before and 4 weeks after laser
      treatment. RESULTS: Both in vitro and in vivo mice data showed a significant
      decrease in growth of pancreatic cancer. Pancreatic cancer cell growth was
      suppressed by 66.1 +/- 0.2%, n = 12, P < 0.01, ANOVA. Subcutaneous shoulder
      tumors were suppressed by 91.2 +/- 2.3%, n = 12, P < 0.001, and orthotopically
      grown pancreatic tumors were suppressed by 42.2 +/- 8.1%, n = 12, P < 0.05,
      compared to pretreatment sizes. Data expressed as percentage reduction vs paired
      controls in the MTT assay and vs pre-photodynamic therapy in mice experiments.
      Paired Student's t tests were performed vs pretreatment sizes. CONCLUSION: Both
      in vitro and in vivo results revealed a significant decrease in pancreatic cancer
      cell growth. Laser or dye alone had no effect, indicating that intratumor
      hypericin and laser therapy may prove useful in unresectable pancreatic cancer.

PMID- 10945956
TI  - Nerve distribution in hemangiomas depends on the proliferative state of the
      microvasculature.
AB  - Hemangiomas appear at birth and undergo gradual regression within several years.
      Recent published studies have documented increased nerve numbers in port-wine
      stains and intramuscular vascular tumors. The aim of this study was to establish
      a relationship between angiogenesis and nerve growth in lesions that undergo
      neovascular proliferation followed by vessel involution. Twenty-two hemangiomas
      and arteriovenous malformations were studied using indirect immunocytochemistry
      with antibodies against the nerve markers protein gene product 9.5 (PGP 9.5) and
      calcitonin gene-related peptide (CGRP). Nerves and vessels were counted and
      compared. Our results indicate that PGP 9.5(+) and CGRP(+) nerves were most
      numerous in growing hemangiomas and numbers were reduced in involuting
      hemangiomas and vascular malformations. The percentage of CGRP(+) sensory nerves
      was markedly increased in growing hemangiomas (45.3%) compared with involuting
      hemangiomas (21.2). These data indicate that hemangiomas with increasing
      neovascularization have increased sensory nerve growth. Sensory nerve-derived
      neuropeptides are known to act as endothelial cell mitogens and may contribute to
      the angiogenesis in these vascular tumors. Conversely, angiogenic endothelial
      cells may secrete mediators that promote nerve fiber growth. These results
      suggest that endothelial cell proliferation and sensory nerve fiber growth may be
      closely related.

PMID- 10945957
TI  - Topical application of amrinone (a selective phosphodiesterase III inhibitor) for
      relief of vasospasm.
AB  - BACKGROUND: Amrinone, a selective phosphodiesterase III inhibitor, is an agent
      that possesses a combination of positive inotropic and vasodilating properties as
      a result of preventing the degradation of cAMP, and it has recently been licensed
      for the treatment of heart failure. The aim of this study was to investigate the
      potential therapeutic application of amrinone to resolve vasospasm, which is the
      major problem in reconstructive surgery. In this study its effect was compared
      with that of lidocaine, the most commonly used topical vasodilating agent
      clinically. MATERIALS AND METHODS: The probe of an ultrasonic transit-time volume
      flowmeter was applied to the femoral artery of rats to measure blood flow. After
      a baseline recording was obtained, 0.03 ml of epinephrine was applied topically
      to induce vasospasm. The vessels were then immersed in 1 ml of amrinone (5
      mg/ml), 10% lidocaine hydrochloride, or normal physiological saline solution for
      1 min in an attempt to resolve the spasm. In another group of animals, no
      solution was used following administration of epinephrine to allow observation of
      spontaneous resolution of the vasospasm over time. RESULTS: The results showed an
      essentially immediate spasm-resolving effect in both the amrinone group and the
      lidocaine group. The amrinone group showed a significantly greater degree of
      maximum increase in blood flow than the lidocaine group. The effect of lidocaine
      decreased with time, whereas amrinone had a more lasting effect. CONCLUSIONS: The
      findings suggest that amrinone could be used as an effective topical vasodilating
      agent to resolve vasospasm in reconstructive surgery.

PMID- 10945958
TI  - L-Selectin and chemokine response after liver ischemia and reperfusion.
AB  - BACKGROUND: L-selectin plays an important role in the early phase of PMNs
      recruitment in the hepatic microvasculature following liver ischemia and
      reperfusion (I/R). Leukocyte cytokine chemoattractants (chemokines) cause
      polymorphonuclear neutrophil (PMN) activation in I/R injury. In this study, we
      examined the role of L-selectin in the production of chemokines in the liver and
      lung inflammatory response following 90 min of warm ischemia. STUDY DESIGN:
      Thirty-six C57BL/6 mice were subjected to partial liver ischemia for a period of
      90 min. Three groups of animals were included (n = 12 per group)-sham group,
      ischemic control, and the ischemic group receiving monoclonal antibody against L
      selectin. We evaluated at 3 h: liver injury measurements, serum chemokines (MIP-2
      and MIP-1alpha), liver and lung tissue myeloperoxidase (MPO), and liver and lung
      histology. Statistical analysis included ANOVA, Student-Newman-Keuls', and
      Kruskal-Wallis multiple comparison Z-value tests. RESULTS: The ischemic group
      treated with anti-L-selectin showed significant decreases in liver enzyme levels
      and a marked decrease in serum MIP-2 (P < 0.05) when compared to ischemic
      controls. No reduction in serum MIP-1alpha was noted; however, neutrophil
      infiltration was significantly ameliorated in the liver and in the lung, as
      reflected by decreased MPO levels (P < 0.05). Improved histopathological features
      were observed in the anti-L-selectin-treated group compared to ischemic controls
      in the liver and the lung. CONCLUSIONS: Our study suggests an important role for
      L-selectin in the pathogenesis of liver I/R and the production of chemokines.
      Anti-L-selectin treatment resulted in improved liver function, decreased
      neutrophil infiltration, and decreased MIP-2 chemokine response.

PMID- 10945959
TI  - Vitamin E succinate promotes breast cancer tumor dormancy.
AB  - BACKGROUND: Vitamin E succinate (VES) is the most potent antitumor analogue of
      vitamin E. Despite many reports of VES's antitumor activity in vitro, there is
      little information about its antitumor effects in vivo. MATERIALS AND METHODS: We
      investigated the effect of VES on the growth of human breast cancer cells in
      vitro and in vivo. RESULTS: VES decreased cell viability in MDA-MB-231 and MCF-7
      human breast cancer cells. Although VES increased apoptosis in MDA-MB-231 cells,
      it had no effect on apoptosis in MCF-7 cells. The inhibitory effect of VES on
      cell growth was specific for the intact molecule because a markedly reduced
      effect was noted when either vitamin E or succinic acid was administered alone.
      VES inhibited the growth of MDA-MB-231 cells in nude mice. Also, VES was found to
      inhibit vascular endothelial growth factor (VEGF) gene expression in MDA-MB-231
      cells. CONCLUSIONS: VES inhibits the growth of breast cancer cells in vitro and
      in vivo. This is the first report of VES inhibition of established tumor growth
      in vivo. The mechanism of VES's in vivo effects may involve inhibition of tumor
      angiogenesis since VES inhibits VEGF gene expression.

PMID- 10945960
TI  - Pancreatitis-associated ascitic fluid increases intracellular Ca(2+)
      concentration on hepatocytes.
AB  - BACKGROUND: We have reported that pancreatitis-associated ascitic fluid (PAAF)
      contains a cytotoxic factor(s) inducing apoptosis on renal tubular cells and
      hepatocytes. It has been suggested that elevation of intracellular Ca(2+)
      concentration ([Ca(2+)](i)) is associated with the development of cell damage and
      apoptosis. METHODS: To clarify the mechanism of hepatocellular injury in acute
      pancreatitis, the effect of PAAF on hepatocyte [Ca(2+)](i) was investigated.
      Primary cultures of rat hepatocytes were loaded with Fura-2/acetoxymethyl, and
      the changes of [Ca(2+)](i) were measured using spectrofluorometer. RESULTS: The
      baseline of hepatocyte [Ca(2+)](i) was 172 +/- 17 nM. [Ca(2+)](i) increased from
      1 min after the addition of PAAF in a dose-dependent manner. Fractionation of
      PAAF revealed only one fraction (molecular weight >/= 5 x 10(4)) possessed both
      [Ca(2+)](i) elevation activity and cytotoxic activity. Neither 8-(N,N-diethyl
      amino) octyl-3,4,5-trimethoxybenzoate (TMB-8) nor thapsigargin inhibited the PAAF
      evoked [Ca(2+)](i) elevation. Chelation of extracellular Ca(2+) by ethylene
      glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) prevented
      the elevation of [Ca(2+)](i), but verapamil did not prevent it. Platelet
      activating factor antagonist (TCV-309) blocked the PAAF-elicited [Ca(2+)](i)
      elevation. Pancreatitis-associated serum also increased hepatocyte [Ca(2+)](i).
      Moreover, PAAF increased [Ca(2+)](i) on Madin-Darby canine kidney cells in a dose
      dependent manner. CONCLUSIONS: These results suggest that the dramatic elevation
      of hepatocyte [Ca(2+)](i) due to PAAF may be closely related to the
      hepatocellular injury in severe acute pancreatitis and that platelet-activating
      factor may play a pivotal role in increasing hepatocyte [Ca(2+)](i). Elevation of
      [Ca(2+)](i) in various cells may be involved in the mechanism of multiple organ
      failure in this disease.

PMID- 10945961
TI  - Administration of opiate receptor antagonist inhibits mucosal atrophy of the gut
      in fasting rats.
AB  - OBJECTIVE: The objective of this study was to determine whether the opiate mu
      receptor antagonist naloxone would prevent atrophy of the gut in 24-h-fasted
      rats. METHODS: Male Sprague-Dawley rats (n = 76, body weight 200-225 g) were
      catheterized in the jugular vein on Day 0. The rats were fed standard rat chow
      for 4 days. On Day 4, the diet was changed to the standard liquid diet, and the
      rats were allowed free access to the liquid diet. On Day 7, the rats were
      randomized into five groups: (1) free fed, (2) free fed plus naloxone, (3) pair
      fed, (4) fasting, (5) free fed plus morphine, (6) fasting plus naloxone. Either
      naloxone (0.16 mg/kg/h) or morphine (0. 21 mg/kg/h) was continuously infused via
      venous catheter for 24 h. On Day 8, 24 h after fasting or free feeding, the
      animals were sacrificed. RESULTS: Twenty-four hours of fasting caused atrophy of
      the jejunum and elevated morphine levels in the brain (free fed, 931. 3 +/- 122.3
      fmol/g, vs fasting, 1419.0 +/- 150.0, P < 0.05). Morphine infusion reduced villus
      height, mucosal weight, and protein content in jejunum as compared with the free
      fed rats receiving saline. Administration of naloxone caused an increase in
      villus height (fasting, 587.0 +/- 25.8 microm, vs fasting plus naloxone, 670.0 +/
      17.4, P < 0.05), mucosal weight (fasting, 17.4 +/- 1.8 mg/cm, vs fasting plus
      naloxone, 22.6 +/- 1.9, P < 0.05), and protein content (fasting, 13.5 +/- 0.7
      microg/cm, vs fasting plus naloxone, 16.7 +/- 0.6, P < 0.05) in jejunum.
      CONCLUSION: Mucosal atrophy of the jejunum is caused by endogenous opioid in
      fasting rats.

PMID- 10945962
TI  - Regulation of intestinal blood flow.
AB  - The gastrointestinal system anatomically is positioned to perform two distinct
      functions: to digest and absorb ingested nutrients and to sustain barrier
      function to prevent transepithelial migration of bacteria and antigens.
      Alterations in these basic functions contribute to a variety of clinical
      scenarios. These primary functions intrinsically require splanchnic blood flow at
      both the macrovascular and microvascular levels of perfusion. Therefore, a
      greater understanding of the mechanisms that regulate intestinal vascular
      perfusion in the normal state and during pathophysiological conditions would be
      beneficial. The purpose of this review is to summarize the current understanding
      regarding the regulatory mechanisms of intestinal blood flow in fasted and fed
      conditions and during pathological stress.

PMID- 10945963
TI  - Trauma mannequin assessment of management skills of surgical residents after
      advanced trauma life support training.
AB  - BACKGROUND: We tested the effectiveness of Advanced Trauma Life Support (ATLS)
      training among surgical residents using a specially designed mannequin. MATERIALS
      AND METHODS: Thirty-two Postgraduate Year I surgical residents were randomly
      assigned to two groups of 16 each. By use of a trauma mannequin, the 32
      residents' performances were scored using four trauma scenarios before 16
      residents (ATLS group) completed a standard ATLS course. Performances were also
      scored after the ATLS course on another four trauma scenarios. The scores were
      standardized to a maximum of 20 for each scenario. Organized Approach scores with
      a range of 1 to 5, Priority scores ranging from 1 to 7, and global ratings of
      Honors, Pass, Borderline, or Fail were assigned for each clinical scenario.
      RESULTS: The pre-ATLS assessment scores were similar for both groups ranging
      between 9.4 +/- 3.5 and 11.4 +/- 2.9 for the ATLS group and between 10.2 +/- 3.8
      and 11.4 +/- 3.9 for the non-ATLS group. The ATLS group scores ranged from 16.0
      +/- 1.3 to 17.4 +/- 3.1 after the course and the non-ATLS group scores ranged
      from 11.4 +/- 4.2 to 12.9 +/- 4.0 (P < 0.05). Pre-ATLS Organized Approach scores
      were 2.9 +/- 1.0 and 2.7 +/- 1.1 (NS) for the ATLS and non-ATLS groups,
      respectively, with post-ATLS scores being significantly higher in the ATLS group
      (4.9 +/- 1.2 compared with 2.8 +/- 1.2 for the non-ATLS group, P < 0. 05).
      Initial Priority scores were also similar for both groups (3.2 +/- 1.4 for the
      ATLS group and 3.3 +/- 2.0 for the non-ATLS group). Post-ATLS Priority scores
      were significantly higher (6.4 +/- 1.4) in the ATLS group compared with 4.2 +/-
      1.9 for the non-ATLS group (P < 0.05). The pre-ATLS global ratings were similar
      for both groups and post-ATLS there were 10 Honors ratings in the ATLS group and
      none for the control group. CONCLUSIONS: Using a trauma mannequin, for
      assessment, surgical residents completing the ATLS course demonstrated superior
      resuscitation skills compared with a non-ATLS group.

PMID- 10945964
TI  - The organization of replicon clusters is not affected by polyamine depletion.
AB  - Earlier investigations have shown that polyamine depletion affects DNA
      replication negatively. DNA is synthesized in replicons which are gathered in
      replicon clusters. DNA replication is initiated simultaneously in every replicon
      of a replicon cluster. By pulse labeling cells with the thymidine analog
      bromodeoxyuridine and then detecting bromodeoxyuridine in situ with
      immunofluorescence, replicon clusters can be studied. We have used this method to
      investigate the effects of 2-difluoromethylornithine (DFMO)- and 4-amidinoindan-1
      one 2'-amidinohydrazone (CGP 48664)-mediated polyamine depletion on the
      organization of replicon clusters. The cells were studied by fluorescence
      microscopy and confocal laser scanning microscopy. Our studies give at hand that
      neither the number nor the distribution of replicon clusters were affected even
      after 4 days of treatment with 5 mM DFMO or 20 microM CGP 48664, indicating that
      polyamine depletion did not affect the organization of replicon clusters.
      However, the fluorescence intensity of the replicon clusters was much lower in
      inhibitor-treated cells. The results indicate that the impaired DNA replication
      observed in polyamine-depleted cells is not due to an effect on the initiation
      step of DNA replication, but rather on the elongation process. To confirm that it
      is possible to observe changes in the organization of replicon clusters using
      bromodeoxyuridine, we treated the cells with various drugs that affect DNA
      replication. Aphidicolin, which inhibits DNA elongation, gave results similar to
      those of DFMO and CGP 48664.

PMID- 10945965
TI  - Automated electron tomography of the septal pore cap in Rhizoctonia solani.
AB  - Dolipore septa and septal pore caps (SPCs) in filamentous basidiomycetes may play
      an important role in maintaining the integrity of hyphal cells. We have
      investigated the ultrastructure of the dolipore septum and the SPC in Rhizoctonia
      solani hyphal cells after high-pressure freezing, freeze substitution, and Spurr
      embedding. We visualized the SPC with associated cell ultrastructures in three
      dimensions by automated electron tomography of thick-sectioned cells, followed by
      3D tomographic reconstructions. Using these methods we were able to document the
      passage of mitochondria through the SPC, small tubular membranous structures at
      the entrance of the septal pore channel, filamentous structures connecting the
      inner side of the SPC with pore-plugging material, thin filaments anchoring the
      pore-plugging material with the plasma membrane, small vesicles attached to the
      plugging material, and tubular endoplasmic reticulum continuous with the base of
      the SPC. We hypothesize that the SPC, the filamentous structures, the plugging
      material, and the endoplasmic reticulum act in a coordinated fashion to maintain
      cellular integrity, intercellular communication, and the transport of solutes and
      cell organelles in the filamentous fungus R. solani.

PMID- 10945966
TI  - The structure of the C949S mutant human alpha(2)-macroglobulin demonstrates the
      critical role of the internal thiol esters in its proteinase-entrapping
      structural transformation.
AB  - A three-dimensional reconstruction of a protein-engineered mutant alpha(2)
      macroglobulin (alpha(2)M) in which a serine residue was substituted for the
      cysteine 949 (C949S), making it unable to form internal thiol ester moieties, was
      compared with native and methylamine-transformed alpha(2)Ms. The native alpha(2)M
      structure consists of two oppositely oriented Z-shaped strands. Thiol ester
      cleavage following an encounter with a proteinase or a nucleophilic attack by
      methylamine causes a structural transformation in which the strands assume an
      opposite handedness and a significant portion of the protein density migrates
      from the distal ends of the molecule toward the center. The C949S mutant showed a
      protein density distribution very similar to that of transformed alpha(2)M, with
      a compact central region of protein density connected to two receptor-binding
      arms on each end of the molecule. Since no particle shapes characteristic of
      native or half-transformed alpha(2)Ms were seen in electron micrographs and the
      C949S mutant and alpha(2)M-methylamine structures are highly similar, we conclude
      that the intact thiol esters maintain native alpha(2)M in a quasi-stable state.
      In their absence, alpha(2)M folds into the more stable transformed structure,
      which displays the functionally important receptor-binding domains and contains
      the proteinase-entrapping internal cavity.

PMID- 10945967
TI  - Self-assembly properties of recombinant engineered amelogenin proteins analyzed
      by dynamic light scattering and atomic force microscopy.
AB  - Dynamic light scattering (DLS) analysis together with atomic force microscopy
      (AFM) imaging was applied to investigate the supramolecular self-assembly
      properties of a series of recombinant amelogenins. The overall objective was to
      ascertain the contribution of certain structural motifs in amelogenin to protein
      protein interactions during the self-assembly process. Mouse amelogenins lacking
      either amino- or carboxy-terminal domains believed to be involved in self
      assembly and amelogenins having single or double amino acid mutations identical
      to those found in cases of amelogenesis imperfecta were analyzed. The
      polyhistidine-containingfull-length recombinant amelogenin protein [rp(H)M180]
      generated nanospheres with monodisperse size distribution (hydrodynamic radius of
      20.7 +/- 2.9 nm estimated from DLS and 16.1 +/- 3.4 nm estimated from AFM
      images), comparable to nanospheres formed by full-length amelogenin rM179 without
      the polyhistidine domain, indicating that this histidine modification did not
      interfere with the self-assembly process. Deletion of the N-terminal self
      assembly domain from amelogenin and their substitution by a FLAG epitope ("A"
      domain deletion) resulted in the formation of assemblies with a heterogeneous
      size distribution with the hydrodynamic radii of particles ranging from 3 to 38
      nm. A time-dependent dynamic light scattering analysis of amelogenin molecules
      lacking amino acids 157 through 173 and containing a hemagglutinin epitope ("B"
      domain deletion) resulted in the formation of particles (21.5 +/- 6.8 nm) that
      fused to form larger particles of 49.3 +/- 4.3 nm within an hour. Single and
      double point mutations in the N-terminal region resulted in the formation of
      larger and more heterogeneous nanospheres. The above data suggest that while the
      N-terminal A-domain is involved in the molecular interactions for the formation
      of nanospheres, the carboxy-terminal B-domain contributes to the stability and
      homogeneity of the nanospheres, preventing their fusion to larger assemblies.
      These in vitro findings support the notion that the proteolytic cleavage of
      amelogenin at amino- and carboxy-terminii occurring during enamel formation
      influences amelogenin to amelogenin interactions during self-assembly and hence
      alters the structural organization of the developing enamel extracellular matrix,
      thus affecting enamel biomineralization.

PMID- 10945968
TI  - In situ imaging of detergent-resistant membranes by atomic force microscopy.
AB  - Purified detergent-resistant membranes (DRMs) are powerful tools for the
      biochemical study of plasma membrane domains. To what extent these isolated DRMs
      correspond to native membrane domains remains, however, a matter of debate. The
      most immediate question to be answered concerns the in situ size range of DRMs, a
      determination that escapes classical microscopy techniques. In this study we show
      that in situ three-dimensional images of a material as fragile as Triton X-100
      treated cells can be obtained, in buffer, by tapping mode atomic force
      microscopy. These images establish that, prior to the isolation procedure, the
      detergent plasma membrane fragments form domains whose size frequently exceeds 15
      20 microm(2). This DRMs size range is about 1 order of magnitude higher than that
      estimated for the larger microdomains of living cells, which strongly suggests
      that membrane microdomains rearrange into larger DRMs during Triton X-100
      treatment. Concomitantly, the images also reveal the presence of the
      cytoskeleton, which is resistant to detergent extraction, and suggest that, in
      situ, DRMs are associated with the membrane cytoskeleton.

PMID- 10945969
TI  - Basement membrane macromolecules: insights from atomic force microscopy.
AB  - The major macromolecules of basement membranes-collagen IV, laminin-1, and
      heparan sulfate proteoglycan (HSPG)-have been analyzed by atomic force microscopy
      (AFM), both individually and in combination with each other. The positions of
      laminin binding to collagen IV were mapped and compared with the positions of
      imperfections in the amino acid sequence of collagen IV; the apparent molecular
      volumes of the HSPG proteoglycans were measured and used to estimate the
      corresponding molecular weights. Even the thin, thread-like strands of the
      polyanion heparan sulfate can be visualized with AFM without staining, coating,
      or fixation. These strands are single polysaccharide chains and are thus thinner
      than single-stranded DNA. The heparan sulfate strands in HSPG are necessary for
      protein filtration in kidney basement membranes. We propose that these thin
      strands filter proteins by functioning as an entropic brush-i.e., that they
      filter proteins by their constant thermally driven motion in the basement
      membrane. These AFM analyses in air are a step toward AFM analyses under fluid of
      basement membrane macromolecules interacting with each other.

PMID- 10945970
TI  - Long-depth imaging of specific gene expressions in whole-mount mouse embryos with
      single-photon excitation confocal fluorescence microscopy and FISH.
AB  - Long-depth imaging of specific gene expression in the midgestation whole-mount
      mouse embryo (WME) is demonstrated with single-photon excitation (1PE) confocal
      fluorescence microscopy and fluorescence in situ hybridization. Expression
      domains of Pax-6 mRNA transcripts were labeled with an in situ hybridization
      probe that is a RNA sequence complementary to the cloned gene fragment and were
      rendered visible using two fluorochrome-conjugated antibodies that fluoresce at
      peak wavelengths of lambda(F) = 0.525 microm and lambda(F) = 0. 580 microm,
      respectively. Distributions of Pax-6 mRNA domains as deep as 1000 microm in the
      day 9.5 WME were imaged with a long-working-distance (13.6 mm) objective lens
      (magnification 5x). The scattering problem posed by the optically thick WME
      sample is alleviated by careful control of the detector pinhole size and the
      application of simple but fast postdetection image enhancement techniques, such
      as space and wavelength averaging to produce high-quality fluorescence images. A
      three-dimensional reconstruction that clearly shows the Pax-6 mRNA expression
      domains in the forebrain, diencephalon, optic cup, and spinal cord of the day 9.5
      WME is obtained. The advantages of 1PE confocal fluorescence imaging over two
      photon excitation fluorescence imaging are discussed for the case of long-depth
      imaging in highly scattering media. Imaging in midgestation WMEs at optical
      depths of more than 350 microm has not yet been realized with two-photon
      fluorescence excitation.

PMID- 10945971
TI  - The otoconia of the guinea pig utricle: internal structure, surface exposure, and
      interactions with the filament matrix.
AB  - A unique feature of the vertebrate gravity receptor organs, the saccule and
      utricle, is the mass of biomineral structures, the otoconia, overlying a
      gelatinous matrix also called "otoconial membrane" on the surface of the sensory
      epithelium. In mammals, otoconia are deposits of calcium carbonate in the form of
      composite calcite crystals. We used quick-freezing, deep etching to examine the
      otoconial mass of the guinea pig utricle. The deep-etching step exposed large
      expanses of intact and fractured otoconia, showing the fine structure and
      relationship between their internal crystal structure, their surface components,
      and the filament matrix in which they are embedded. Each otoconium has a compact
      central core meshwork of filaments and a composite outer shell of ordered
      crystallites and macromolecular aggregates. A distinct network of 20-nm beaded
      filaments covers the surface of the otoconia. The otoconia are interconnected and
      secured to the gelatinous matrix by surface adhesion and by confinement within a
      loose interotoconial filament matrix. The gelatinous matrix is a dense network
      made of yet another type of filament, 22 nm in diameter, which are cross-linked
      by shorter filaments, characteristically 11 nm in diameter. Our freeze-etching
      data provide a structural framework for considering the molecular nature of the
      components of the otoconial complex, their mechanical properties, and the degree
      of biological versus chemical control of otoconia biosynthesis.

PMID- 10945972
TI  - Crystallization and preliminary X-Ray diffraction analysis of glutaryl-7
      aminocephalosporanic acid acylase from Pseudomonas sp. GK16.
AB  - Glutaryl-7-aminocephalosporanicacid acylase from Pseudomonas sp. GK16 produces
      glutaryl-7-aminocephalosporanic acid, a key intermediate for the synthesis of
      cephem antibiotics. Sequence alignment suggests that the enzyme may belong to the
      N-terminal nucleophile hydrolase superfamily including penicillin G acylase. The
      enzyme is an (alphabeta)(2) heterotetramer of two nonidentical subunits. These
      subunits are derived from a nascent precursor polypeptide that is cleaved
      proteolytically through a two-step autocatalytic process upon folding. The enzyme
      has been crystallized using the vapor diffusion method. A bipyramidal crystal
      form was obtained from a solution containing polyethylene glycol (MW 3350) and
      calcium chloride. Complete diffraction data sets have been collected up to 2.8 A
      resolution. The crystal is tetragonal with the space group P4(1)2(1)2 or
      P4(3)2(1)2 and the unit cell parameters are a = b = 73.5 A, c = 380.3 A.
      Considerations of the possible values of V(m) account for the presence of a
      tetramer in the asymmetric unit.

PMID- 10945974
TI  - Regulatable expression of p21-activated kinase-1 promotes anchorage-independent
      growth and abnormal organization of mitotic spindles in human epithelial breast
      cancer cells.
AB  - Stimulation of growth factor signaling has been implicated in the development of
      invasive phenotypes and the activation of p21-activated kinase (Pak1) in human
      breast cancer cells (Adam, L., Vadlamudi, R., Kondapaka, S. B., Chernoff, J.,
      Mendelsohn, J., and Kumar, R. (1998) J. Biol. Chem. 273, 28238-28246; Adam, L.,
      Vadlamudi, R., Mandal, M., Chernoff, J., and Kumar, R. (2000) J. Biol. Chem. 275,
      12041-12050). To study the role of Pak1 in the regulation of motility and growth
      of breast epithelial cells, we developed human epithelial MCF-7 clones that
      overexpressed the kinase-active T423E Pak1 mutant under an inducible tetracycline
      promoter or that stably expressed the kinase-active H83L,H86L Pak1 mutant, which
      is deficient in small GTPase binding sites. The expression of both T423E and
      H83L,H86L Pak1 mutants in breast epithelial cells was accompanied by increased
      cell motility without any apparent effect on the growth rate of cells. The T423E
      Pak1 mutant was primarily localized to filopodia, and the H83L,H86L Pak1 mutant
      was primarily localized to ruffles. Cells expressing T423E Pak1 exhibited a
      regulatable stimulation of mitogen-activated protein kinase and Jun N-terminal
      kinase activities. The expression of kinase-active Pak1 mutants significantly
      stimulated anchorage-independent growth of cells in soft agar in a preferential
      mitogen-activated protein kinase-sensitive manner. In addition, regulatable
      expression of kinase-active Pak1 resulted in an abnormal organization of mitotic
      spindles characterized by appearance of multiple spindle orientations. We also
      provide evidence to suggest a close correlation between the status of Pak1 kinase
      activity and base-line invasiveness of human breast cancer cells and breast tumor
      grades. This study is the first demonstration of Pak1 regulation of anchorage
      independent growth, potential Pak1 regulation of invasiveness, and abnormal
      organization of mitotic spindles of human epithelial breast cancer cells.

PMID- 10945975
TI  - BRCA1 physically and functionally interacts with ATF1.
AB  - BRCA1, a breast and ovarian cancer susceptibility gene, encodes a 220-kDa protein
      whose precise biochemical function remains unclear. BRCA1 contains an N-terminal
      RING finger that mediates protein-protein interaction. The C-terminal domain of
      BRCA1 (BRCT) can activate transcription and interacts with RNA polymerase
      holoenzyme. Using the yeast two-hybrid system, we identified an interaction
      between the BRCA1 RING finger and ATF1, a member of the cAMP response element
      binding protein/activating transcription factor (CREB/ATF) family. We demonstrate
      that BRCA1 and ATF1 can physically associate in vitro, in yeast, and in human
      cells. BRCA1 stimulated transcription from a cAMP response element reporter gene
      in transient transfections. BRCA1 also stimulated transcription from a natural
      promoter, that of tumor necrosis factor-alpha, in a manner dependent on the
      integrity of the cAMP response element. These results implicate BRCA1 in
      transcriptional activation of ATF1 target genes, some of which are involved in
      the transcriptional response to DNA damage.

PMID- 10945976
TI  - A novel protein with homology to the junctional adhesion molecule.
      Characterization of leukocyte interactions.
AB  - We have cloned a novel cDNA belonging to the Ig superfamily that shows 44%
      similarity to the junctional adhesion molecule (JAM) and maps to chromosome
      21q21.2. The open reading frame of JAM2 predicts a 34-kDa type I integral
      membrane protein that features two Ig-like folds and three N-linked glycosylation
      sites in the extracellular domain. A single protein kinase C phosphorylation
      consensus site and a PDZ-binding motif are present in the short intracellular
      tail. Heterologous expression of JAM2 in Chinese hamster ovary cells defined a 48
      kDa protein that localizes predominantly to the intercellular borders. Northern
      blot analysis showed that JAM2 is preferentially expressed in the heart. JAM2
      homotypic interactions were demonstrated by the ability of JAM2-Fc to capture
      JAM2-expressing Chinese hamster ovary cells. We further showed that JAM2, but not
      JAM1, is capable of adhering to the HSB and HPB-ALL lymphocyte cell lines.
      Neutralizing mouse anti-JAM2 polyclonal antibodies provided evidence against
      homotypic interactions in this assay. Biotinylation of HSB cell membranes
      revealed a 43-kDa counter-receptor that precipitates specifically with JAM2-Fc.
      These characteristics of JAM2 led us to hypothesize a role for this novel protein
      in adhesion events associated with cardiac inflammatory conditions.

PMID- 10945977
TI  - Ca(2+)-dependent regulation of the motor activity of myosin V.
AB  - Mouse myosin V constructs were produced that consisted of the myosin motor domain
      plus either one IQ motif (M5IQ1), two IQ motifs (M5IQ2), a complete set of six IQ
      motifs (SHM5), or the complete IQ motifs plus the coiled-coil domain (thus
      permitting formation of a double-headed structure, DHM5) and expressed in Sf9
      cells. The actin-activated ATPase activity of all constructs except M5IQ1 was
      inhibited above pCa 5, but this inhibition was completely reversed by addition of
      exogenous calmodulin. At the same Ca(2+) concentration, 2 mol of calmodulin from
      SHM5 and DHM5 or 1 mol of calmodulin from M5IQ2 were dissociated, suggesting that
      the inhibition of the ATPase activity is due to dissociation of calmodulin from
      the heavy chain. However, the motility activity of DHM5 and M5IQ2 was completely
      inhibited at pCa 6, where no dissociation of calmodulin was detected. Inhibition
      of the motility activity was not reversed by the addition of exogenous
      calmodulin. These results indicate that inhibition of the motility is due to
      conformational changes of calmodulin upon the Ca(2+) binding to the high affinity
      site but is not due to dissociation of calmodulin from the heavy chain.

PMID- 10945978
TI  - A novel model system for characterization of phagosomal maturation,
      acidification, and intracellular collagen degradation in fibroblasts.
AB  - Intracellular collagen degradation by fibroblasts is an important but poorly
      understood pathway for the physiological remodeling of mature connective tissues.
      The objective of this study was to determine whether gingival fibroblasts that
      express endogenous alpha(2)beta(1) integrin, the collagen receptor, would exhibit
      the cellular machinery required for phagosomal maturation and collagen
      degradation. There was a time-dependent increase of collagen bead internalization
      and a time-dependent decrease of bead-associated alpha(2)beta(1) integrin after
      initial bead binding. beta-Actin and gelsolin associated transiently with beads
      (0-30 min) followed by LAMP-2 (60-240 min) and cathepsin B (30-240 min).
      Cytochalasin D prevented phagosome formation and also prevented the sequential
      fusion of early endosomes with lysosomes. Collagen bead-associated pH was
      progressively reduced from 7.25 to 5.4, which was contemporaneous with
      progressive increases in degradation of bead-associated collagen (30-120 min).
      Concanamycin blocked acidification of phagolysosomes and collagen degradation but
      not phagosome maturation. Phagosomal acidification was partly dependent on
      elevated intracellular calcium. These studies demonstrate that the cellular
      machinery required for intracellular collagen degradation in fibroblasts closely
      resembles the vacuolar system in macrophages.

PMID- 10945980
TI  - DNA ligase IV and XRCC4 form a stable mixed tetramer that functions
      synergistically with other repair factors in a cell-free end-joining system.
AB  - Repair of DNA double-strand breaks in mammalian cells occurs via a direct
      nonhomologous end-joining pathway. Although this pathway can be studied in vivo
      and in crude cell-free systems, a deeper understanding of the mechanism requires
      reconstitution with purified enzymes. We have expressed and purified a complex of
      two proteins that are critical for double-strand break repair, DNA ligase IV (DNL
      IV) and XRCC4. The complex is homogeneous, with a molecular mass of about 300,000
      Da, suggestive of a mixed tetramer containing two copies of each polypeptide. The
      presence of multiple copies of DNL IV was confirmed in an experiment where
      different epitope-tagged forms of DNL IV were recovered simultaneously in the
      same complex. Cross-linking suggests that an XRCC4.XRCC4 dimer interface forms
      the core of the tetramer, and that the DNL IV polypeptides are in contact with
      XRCC4 but not with one another. Purified DNL IV.XRCC4 complex functioned
      synergistically with Ku protein, the DNA-dependent protein kinase catalytic
      subunit, and other repair factors in a cell-free end-joining assay. We suggest
      that a dyad-symmetric DNL IV.XRCC4 tetramer bridges the two ends of the broken
      DNA and catalyzes the coordinate ligation of the two DNA strands.

PMID- 10945979
TI  - The heat shock protein 90 antagonist novobiocin interacts with a previously
      unrecognized ATP-binding domain in the carboxyl terminus of the chaperone.
AB  - Heat shock protein 90 (Hsp90), one of the most abundant chaperones in eukaryotes,
      participates in folding and stabilization of signal-transducing molecules
      including steroid hormone receptors and protein kinases. The amino terminus of
      Hsp90 contains a non-conventional nucleotide-binding site, related to the ATP
      binding motif of bacterial DNA gyrase. The anti-tumor agents geldanamycin and
      radicicol bind specifically at this site and induce destabilization of Hsp90
      dependent client proteins. We recently demonstrated that the gyrase inhibitor
      novobiocin also interacts with Hsp90, altering the affinity of the chaperone for
      geldanamycin and radicicol and causing in vitro and in vivo depletion of key
      regulatory Hsp90-dependent kinases including v-Src, Raf-1, and p185(ErbB2). In
      the present study we used deletion/mutation analysis to identify the site of
      interaction of novobiocin with Hsp90, and we demonstrate that the novobiocin
      binding site resides in the carboxyl terminus of the chaperone. Surprisingly,
      this motif also recognizes ATP, and ATP and novobiocin efficiently compete with
      each other for binding to this region of Hsp90. Novobiocin interferes with
      association of the co-chaperones Hsc70 and p23 with Hsp90. These results identify
      a second site on Hsp90 where the binding of small molecule inhibitors can
      significantly impact the function of this chaperone, and they support the
      hypothesis that both amino- and carboxyl-terminal domains of Hsp90 interact to
      modulate chaperone activity.

PMID- 10945981
TI  - Structure-expression relationships of the 15-kDa selenoprotein gene. Possible
      role of the protein in cancer etiology.
AB  - Selenium has been implicated in cancer prevention, but the mechanism and possible
      involvement of selenoproteins in this process are not understood. To elucidate
      whether the 15-kDa selenoprotein may play a role in cancer etiology, the complete
      sequence of the human 15-kDa protein gene was determined, and various
      characteristics associated with expression of the protein were examined in normal
      and malignant cells and tissues. The 51-kilobase pair gene for the 15-kDa
      selenoprotein consisted of five exons and four introns and was localized on
      chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers.
      Two stem-loop structures resembling selenocysteine insertion sequence elements
      were identified in the 3'-untranslated region of the gene, and only one of these
      was functional. Two alleles in the human 15-kDa protein gene were identified that
      differed by two single nucleotide polymorphic sites that occurred within the
      selenocysteine insertion sequence-like structures. These 3'-untranslated region
      polymorphisms resulted in changes in selenocysteine incorporation into protein
      and responded differently to selenium supplementation. Human and mouse 15-kDa
      selenoprotein genes manifested the highest level of expression in prostate,
      liver, kidney, testis, and brain, and the level of the selenoprotein was reduced
      substantially in a malignant prostate cell line and in hepatocarcinoma. The
      expression pattern of the 15-kDa protein in normal and malignant tissues, the
      occurrence of polymorphisms associated with protein expression, the role of
      selenium in differential regulation of polymorphisms, and the chromosomal
      location of the gene may be relevant to a role of this protein in cancer.

PMID- 10945982
TI  - Formation of compound I in the reaction of native myoglobins with hydrogen
      peroxide.
AB  - Reaction of ferric native myoglobin (Mb) with hydrogen peroxide (H(2)O(2)) was
      studied by the aid of stopped-flow rapid-scan spectrophotometry. In contrast to
      the results in previous studies where compound I was reported to be undetectable,
      both sperm whale and horse heart metmyoglobins (metMbs) formed a significant
      quantity of compound I, an oxoferryl porphyrin pi-cation radical (Por(+)
      Fe(IV)(O)), during their reactions with H(2)O(2). With both kinds of Mbs,
      formation of compound I was more clearly observed in D(2)O than in H(2)O. The
      compound thus formed was capable of performing monooxygenation of thioanisole to
      methyl phenyl sulfoxide and a 2-electron oxidation of H(2)O(2) giving O(2) and
      H(2)O as products. It was also converted into ferryl myoglobin (Por-Fe(IV)(O)
      globin(+)) spontaneously. Rate constants for these reactions and that for a
      direct conversion of metMb to ferryl Mb through the homolysis of H(2)O(2) were
      determined. These results established unambiguously that native metMb can form
      both compound I and ferryl Mb upon reaction with H(2)O(2) and that these high
      valent iron compounds serve as essential intermediates in Mb-assisted
      peroxidative reactions. The observed deuterium effect on the apparent stability
      of compound I was attributable to that effect on the hydrogen abstraction step in
      the 2-electron oxidation of H(2)O(2) by compound I.

PMID- 10945983
TI  - Molecular characterization of a hyperinducible, surface membrane-anchored, class
      I nuclease of a trypanosomatid parasite.
AB  - The 3'-nucleotidase/nuclease (3'-NT/NU) is a surface enzyme unique to
      trypanosomatid parasites. These organisms lack the pathway for de novo purine
      biosynthesis and thus are entirely dependent upon their hosts to supply this
      nutrient for their survival, growth, and multiplication. The 3'-NT/NU is involved
      in the salvage of preformed purines via the hydrolysis of either 3'-nucleotides
      or nucleic acids. In Crithidia luciliae, this enzyme is highly inducible. For
      example, in these organisms purine starvation triggers an approximately 1000-fold
      up-expression of 3'-NT/NU activity. In the present study, we cloned and
      characterized a gene encoding this intriguing enzyme from C. luciliae (Cl).
      Sequence analysis showed that the Cl 3'-NT/NU deduced protein possessed five
      regions, which we defined here as being characteristic of members of the class I
      nuclease family. Further, we demonstrated that the Cl 3'-NT/NU-expressed protein
      possessed both 3'-nucleotidase and nuclease activities. Moreover, we showed that
      the dramatic up-expression of 3'-NT/NU activity in response to purine starvation
      of C. luciliae was concomitant with the approximately 100-fold elevation in
      steady-state mRNA specific for this gene. Finally, results of our nuclear run-on
      analyses demonstrated that such up-regulation in 3'-NT/NU enzyme activity was
      mediated at the posttranscriptional level.

PMID- 10945984
TI  - Ku entry into DNA inhibits inward DNA transactions in vitro.
AB  - Association of the DNA end-binding Ku70/Ku80 heterodimer with the 460-kDa
      serine/threonine kinase catalytic subunit forms the DNA-dependent protein kinase
      (DNA-PK) that is required for double-strand break repair by non-homologous
      recombination in mammalian cells. Recently, we have proposed a model in which the
      kinase activity is required for translocation of the DNA end-binding subunit Ku
      along the DNA helix when DNA-PK assembles on DNA ends. Here, we have questioned
      the consequences of Ku entry into DNA on local DNA processes by using human
      nuclear cell extracts incubated in the presence of linearized plasmid DNA. As two
      model processes, we have chosen nucleotide excision repair (NER) of UVC DNA
      lesions and transcription from viral promoters. We show that although NER
      efficiency is strongly reduced on linear DNA, it can be fully restored in the
      presence of DNA-PK inhibitors. Simultaneously, the amount of NER proteins bound
      to the UVC-damaged linear DNA is increased and the amount of Ku bound to the same
      DNA molecules is decreased. Similarly, the poor transcription efficiency
      exhibited by viral promoters on linear DNA is enhanced in the presence of DNA-PK
      inhibitor concentrations that prevent Ku entry into the DNA substrate molecule.
      The present results show that DNA-PK catalytic activity can regulate DNA
      transactions including transcription in the vicinity of double-strand breaks by
      controlling Ku entry into DNA.

PMID- 10945985
TI  - Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric
      oxide synthase. Implications for mechanism.
AB  - We studied catalysis by tetrahydrobiopterin (H4B)-free neuronal nitric-oxide
      synthase (nNOS) to understand how heme and H4B participate in nitric oxide (NO)
      synthesis. H4B-free nNOS catalyzed Arg oxidation to N(omega)-hydroxy-l-Arg (NOHA)
      and citrulline in both NADPH- and H(2)O(2)-driven reactions. Citrulline formation
      was time- and enzyme concentration-dependent but was uncoupled relative to NADPH
      oxidation, and generated nitrite and nitrate without forming NO. Similar results
      were observed when NOHA served as substrate. Steady-state and stopped-flow
      spectroscopy with the H4B-free enzyme revealed that a ferrous heme-NO complex
      built up after initiating catalysis in both NADPH- and H(2)O(2)-driven reactions,
      consistent with formation of nitroxyl as an immediate product. This differed from
      the H4B-replete enzyme, which formed a ferric heme-NO complex as an immediate
      product that could then release NO. We make the following conclusions. 1) H4B is
      not essential for Arg oxidation by nNOS, although it helps couple NADPH oxidation
      to product formation in both steps of NO synthesis. Thus, the NADPH- or H(2)O(2)
      driven reactions form common heme-oxy species that can react with substrate in
      the presence or absence of H4B. 2) The sole essential role of H4B is to enable
      nNOS to generate NO instead of nitroxyl. On this basis we propose a new unified
      model for heme-dependent oxygen activation and H4B function in both steps of NO
      synthesis.

PMID- 10945986
TI  - Calcium-dependent threonine phosphorylation of nonmuscle myosin in stimulated RBL
      2H3 mast cells.
AB  - Stimulation of RBL-2H3 m1 mast cells through the IgE receptor with antigen, or
      through a G protein-coupled receptor with carbachol, leads to the rapid
      appearance of phosphothreonine in nonmuscle myosin heavy chain II-A (NMHC-IIA).
      We demonstrate that this results from phosphorylation of Thr-1940 by
      calcium/calmodulin-dependent protein kinase II (CaM kinase II), activated by
      increased intracellular calcium. The phosphorylation site in rodent NMHC-IIA was
      localized to the carboxyl terminus of NMHC-IIA distal to the coiled-coil region,
      and identified as Thr-1940 by site-directed mutagenesis. A fusion protein
      containing the NMHC-IIA carboxyl terminus was phosphorylated by CaM kinase II in
      vitro, while mutation of Thr-1940 to Ala eliminated phosphorylation. In contrast
      to rodents, in humans Thr-1940 is replaced by Ala, and human NMHC-IIA fusion
      protein was not phosphorylated by CaM kinase II unless Ala-1940 was mutated to
      Thr. Similarly, co-transfected Ala --> Thr-1940 human NMHC-IIA was phosphorylated
      by activated CaM kinase II in HeLa cells, while wild type was not. In RBL-2H3 m1
      cells, inhibition of CaM kinase II decreased Thr-1940 phosphorylation, and
      inhibited release of the secretory granule marker hexosaminidase in response to
      carbachol but not to antigen. These data indicate a role for CaM kinase
      stimulation and resultant threonine phosphorylation of NMHC-IIA in RBL-2H3 m1
      cell activation.

PMID- 10945987
TI  - Glucosylceramide synthase does not attenuate the ceramide pool accumulating
      during apoptosis induced by CD95 or anti-cancer regimens.
AB  - Ceramide (Cer) accumulating during the execution phase of apoptosis is generated
      from plasma membrane sphingomyelin (SM), which gains access to a sphingomyelinase
      due to phospholipid scrambling (Tepper, A. D., Ruurs, P., Wiedmer, T., Sims, P.,
      Borst, J., and van Blitterswijk, W. J. (2000) J. Cell. Biol. 150, 155-164). To
      evaluate the functional significance of this Cer pool, we aimed to convert it to
      glucosylceramide (GlcCer), by constitutive overexpression of glucosylceramide
      synthase (GCS). Jurkat cells, retrovirally transduced with GCS cDNA, showed a 10
      12-fold increase in GCS activity in vitro and a 7-fold elevated basal GlcCer
      level in vivo. However, Cer accumulating during apoptosis induced by ligation of
      the death receptor CD95, treatment with the anti-cancer drug etoposide, or
      exposure to gamma-radiation was not glycosylated by GCS. Likewise, Cer liberated
      at the plasma membrane by bacterial SMase was not converted by the enzyme. Thus,
      GCS, located at the Golgi, is topologically segregated from Cer produced in the
      plasma membrane. In contrast, de novo synthesized Cer as well as an exogenously
      supplied cell-permeable Cer analog were efficiently glycosylated, apparently due
      to different Cer topology and distinct physicochemical behavior of the synthetic
      Cer species, respectively. Exogenous cell-permeable Cer species, despite their
      conversion by GCS, effectively induced apoptosis. We also observed that GCS
      activity is down-regulated in cells undergoing apoptosis. In conclusion, GCS can
      convert de novo synthesized Cer but not SM-derived Cer, and, therefore, the
      ability of GCS overexpression to protect cells from possible detrimental effects
      of Cer accumulation is limited.

PMID- 10945988
TI  - Association of immature hypophosphorylated protein kinase cepsilon with an
      anchoring protein CG-NAP.
AB  - Protein kinase C (PKC) family requires phosphorylation of itself to become
      competent for responding to second messengers. Much attention has been focused on
      elucidating the role of phosphorylation in PKC activity; however, it remains
      unknown where this modification takes place in the cells. This study examines
      whether anchoring protein is involved in the regulation of PKC phosphorylation. A
      certain population of PKC epsilon in rat brain extracts as well as that expressed
      in COS7 cells was associated with an endogenous anchoring protein CG-NAP
      (centrosome and Golgi localized PKN- associated protein). Pulse chase experiments
      revealed that the associated PKC epsilon was an immature species at the
      hypophosphorylated state. In vitro binding studies confirmed that non- or
      hypophosphorylated PKC epsilon directly bound to CG-NAP via its catalytic domain,
      whereas sufficiently phosphorylated PKC epsilon did not. PKC epsilon mutant at a
      potential phosphorylation site of Thr-566 or Ser-729 to Ala, possessing almost no
      catalytic activity, was associated and co-localized with CG-NAP at
      Golgi/centrosome area. On the other hand, wild type and a phosphorylation
      mimicking mutant at Thr-566 were mainly distributed in cytosol and represented
      second messenger-dependent catalytic activation. These results suggest that CG
      NAP anchors hypophosphorylated PKCepsilon at the Golgi/centrosome area during
      maturation and serves as a scaffold for the phosphorylation reaction.

PMID- 10945989
TI  - Reaction of S-nitrosoglutathione with the heme group of deoxyhemoglobin.
AB  - The mechanism of interaction between S-nitrosoglutathione (GSNO) and hemoglobin
      is a crucial component of hypotheses concerning the role played by S
      nitrosohemoglobin in vivo. We previously demonstrated (Patel, R. P., Hogg, N.,
      Spencer, N. Y., Kalyanaraman, B., Matalon, S., and Darley-Usmar, V. M. (1999) J.
      Biol. Chem. 274, 15487-15492) that transnitrosation between oxygenated hemoglobin
      and GSNO is a slow, reversible process, and that the reaction between GSNO and
      deoxygenated hemoglobin (deoxyHb) did not conform to second order reversible
      kinetics. In this study we have reinvestigated this reaction and show that GSNO
      reacts with deoxyHb to form glutathione, nitric oxide, and ferric hemoglobin.
      Nitric oxide formed from this reaction is immediately autocaptured to form
      nitrosylated hemoglobin. GSNO reduction by deoxyHb is essentially irreversible.
      The kinetics of this reaction depended upon the conformation of the protein, with
      more rapid kinetics occurring in the high oxygen affinity state (i.e.
      modification of the Cysbeta-93) than in the low oxygen affinity state (i.e.
      treatment with inositol hexaphosphate). A more rapid reaction occurred when
      deoxymyoglobin was used, further supporting the observation that the kinetics of
      reduction are directly proportional to oxygen affinity. This observation provides
      a mechanism for how deoxygenation of hemoglobin/myoglobin could facilitate nitric
      oxide release from S-nitrosothiols and represents a potential physiological
      mechanism of S-nitrosothiol metabolism.

PMID- 10945991
TI  - Cys-140 is critical for metabotropic glutamate receptor-1 dimerization.
AB  - Metabotropic glutamate receptor 1 (mGluR1) expresses at the cell surface as
      disulfide-linked dimers and can be reduced to monomers with sulfhydryl reagents.
      To identify the dimerization domain, we transiently expressed in HEK-293 cells a
      truncated version of mGluR1 (RhodC-R1) devoid of the extracellular domain (ECD).
      RhodC-R1 was a monomer in the absence or presence of the reducing agents,
      suggesting that dimerization occurs via the ECD. To identify cysteine residues
      involved in dimerization within the ECD, cysteine to serine point mutations were
      made at three cysteines within the amino-terminal half of the ECD. A mutation at
      positions Cys-67, Cys-109, and Cys-140 all resulted in significant amounts of
      monomers in the absence of reducing agents. The monomeric C67S and C109S mutants
      were not properly glycosylated, failed to reach the cell surface, and showed no
      glutamate response, indicating that these mutant receptors were improperly folded
      and/or processed and thus retained intracellularly. In contrast, the monomeric
      C140S mutant was properly glycosylated, processed, and expressed at the cell
      surface. Phosphoinositide hydrolysis assay showed that the glutamate response of
      the C140S mutant receptor was similar to the wild type receptor. Substitution of
      a cysteine for Ser-129, Lys-134, Asp-143, and Thr-146 on the C140S mutant
      background restored receptor dimerization. Taken together, the results suggest
      that Cys-140 contributes to intermolecular disulfide-linked dimerization of
      mGluR1.

PMID- 10945990
TI  - Peptide and protein library screening defines optimal substrate motifs for
      AKT/PKB.
AB  - AKT was originally identified as a proto-oncogene with a pleckstrin homology and
      Ser/Thr protein kinase domains. Recent studies revealed that AKT regulates a
      variety of cellular functions including cell survival, cell growth, cell
      differentiation, cell cycle progression, transcription, translation, and cellular
      metabolism. To clarify the substrate specificity of AKT, we have used an oriented
      peptide library approach to determine optimal amino acids at positions N-terminal
      and C-terminal to the site of phosphorylation. The predicted optimal peptide
      substrate (Arg-Lys-Arg-Xaa-Arg-Thr-Tyr-Ser*-Phe-Gly where Ser* is the
      phosphorylation site) has similarities to but is distinct from optimal substrates
      that we previously defined for related basophilic protein kinases such as protein
      kinase A, Ser/Arg-rich kinases, and protein kinase C family members. The
      positions most important for high V(max)/K(m) ratio were Arg-3>Arg-5>Arg-7. The
      substrate specificity of AKT was further investigated by screening a lambdaGEX
      phage HeLa cell cDNA expression library. All of the substrates identified by this
      procedure contained Arg-Xaa-Arg-Xaa-Xaa-(Ser/Thr) motifs and were in close
      agreement with the motif identified by peptide library screening. The results of
      this study should help in prediction of likely AKT substrates from primary
      sequences.

PMID- 10945992
TI  - Inhibition of mitogenesis in Balb/c-3T3 cells by Trichostatin A. Multiple
      alterations in the induction and activation of cyclin-cyclin-dependent kinase
      complexes.
AB  - Trichostatin A (TSA), a global repressor of histone deacetylase activity,
      inhibits the proliferation of a number of cell types. However, the identification
      of the mechanisms underlying TSA-mediated growth arrests has remained elusive. In
      order to resolve in more detail the cellular process modulated during the growth
      inhibition induced by TSA, we studied the effect of the drug on G(0)/G(1)
      traverse in mitogen-stimulated quiescent Balb/c-3T3 cells. Cyclin D1 and
      retinoblastoma proteins were induced following the mitogenic stimulation of both
      control and TSA-treated cells, and cyclin D1 formed complexes with CDK4 under
      both conditions. However, cyclin D1-associated kinase was not increased in growth
      arrested cells. The lack of cyclin D-associated kinase was paralleled by an
      accumulation of RB in a hypophosphorylated form, as would be expected. In
      contrast, p130 became partially phosphorylated, accompanied by a marked increase
      in p130-dependent E2F DNA binding activity and a partial release of free E2F-4.
      Despite the presence of E2F complexes not bound to pocket proteins, late G(1) E2F
      dependent gene expression was not observed. The lack of cyclin D1-associated
      kinase in TSA-treated cultures was potentially due to high levels of the cyclin
      dependent inhibitor p27(kip1). However, the modulation of p27(kip1) levels by the
      deacetylase inhibitor cannot be responsible for the induction of the cell cycle
      arrest, since the growth of murine embryo fibroblasts deficient in both p27(kip1)
      and p21(cip1) was also inhibited by TSA. These data support a model in which TSA
      inhibits very early cell cycle traverse, which, in turn, leads to a decrease in
      cyclin D1-associated kinase activation and a repression of late cell cycle
      dependent events. Alterations in early G(0)/G(1) gene expression accompany the
      TSA-mediated growth arrest.

PMID- 10945993
TI  - Phosphorylation of protein kinase Cdelta on distinct tyrosine residues regulates
      specific cellular functions.
AB  - Protein kinase Cdelta (PKCdelta) inhibits proliferation and decreases expression
      of the differentiation marker glutamine synthetase (GS) in C6 glioma cells. Here,
      we report that distinct, specific tyrosine residues on PKCdelta are involved in
      these two responses. Transfection of cells with PKCdelta mutated at tyrosine 155
      to phenylalanine caused enhanced proliferation in response to 12-phorbol 12
      myristate 13-acetate, whereas GS expression resembled that for the PKCdelta wild
      type transfectant. Conversely, transfection with PKCdelta mutated at tyrosine 187
      to phenylalanine resulted in increased expression of GS, whereas the rate of
      proliferation resembled that of the PKCdelta wild-type transfectant. The tyrosine
      phosphorylation of PKCdelta and the decrease in GS expression induced by platelet
      derived growth factor (PDGF) were abolished by the Src kinase inhibitors PP1 and
      PP2. In response to PDGF, Fyn associated with PKCdelta via tyrosine 187. Finally,
      overexpression of dominant negative Fyn abrogated the decrease in GS expression
      and reduced the tyrosine phosphorylation of PKCdelta induced by PDGF. We conclude
      that the tyrosine phosphorylation of PKCdelta and its association with tyrosine
      kinases may be an important point of divergence in PKC signaling.

PMID- 10945994
TI  - Identification and characterization of the human ORC6 homolog.
AB  - A new protein was cloned and identified as the sixth member of the human origin
      recognition complex (ORC). The newly identified 30-kDa protein hsORC6 is 28%
      identical and 49% similar to ORC6p from Drosophila melanogaster, which is
      consistent with the identities and similarities found among the other ORC members
      reported in the two species. The human ORC6 gene is located on chromosome 16q12.
      ORC6 protein level did not change through the cell cycle. Like ORC1, ORC6 did not
      co-immunoprecipitate with other ORC subunits but was localized in the nucleus
      along with the other ORC subunits. Several cellular proteins co
      immunoprecipitated with ORC6, including a 65-kDa protein that was
      hyperphosphorylated in G(1) and dephosphorylated in mitosis. Therefore, unlike
      the tight stoichiometric association of six yeast ORC subunits in one holo
      complex, only a small fraction of human ORC1 and ORC6 is likely to be associated
      with a subcomplex of ORC2, 3, 4, and 5, suggesting differences in the
      architecture and regulation of human ORC.

PMID- 10945996
TI  - High salt-induced conversion of Escherichia coli GroEL into a fully functional
      thermophilic chaperonin.
AB  - The GroE chaperonin system can adapt to and function at various environmental
      folding conditions. To examine chaperonin-assisted protein folding at high salt
      concentrations, we characterized Escherichia coli GroE chaperonin activity in 1.2
      m ammonium sulfate. Our data are consistent with GroEL undergoing a
      conformational change at this salt concentration, characterized by elevated
      ATPase activity and increased exposure of hydrophobic surface, as indicated by
      increased binding of the fluorophore bis-(5, 5')-8-anilino-1-naphthalene sulfonic
      acid to the chaperonin. The presence of the salt results in increased substrate
      stringency and dependence on the full GroE system for release and productive
      folding of substrate proteins. Surprisingly, GroEL is fully functional as a
      thermophilic chaperonin in high concentrations of ammonium sulfate and is stable
      at temperatures up to 75 degrees C. At these extreme conditions, GroEL can
      suppress aggregation and mediate refolding of non-native proteins.

PMID- 10945998
TI  - The light chain binding domain of expressed smooth muscle heavy meromyosin acts
      as a mechanical lever.
AB  - Structural data led to the proposal that the molecular motor myosin moves actin
      by a swinging of the light chain binding domain, or "neck." To test the
      hypothesis that the neck functions as a mechanical lever, smooth muscle heavy
      meromyosin (HMM) mutants were expressed with shorter or longer necks by either
      deleting or adding light chain binding sites. The mutant HMMs were characterized
      kinetically and mechanically, with emphasis on measurements of unitary
      displacements and forces in the laser trap assay. Two shorter necked constructs
      had smaller unitary step sizes and moved actin more slowly than WT HMM in the
      motility assay. A longer necked construct that contained an additional essential
      light chain binding site exhibited a 1.4-fold increase in the unitary step size
      compared with its control. Kinetic changes were also observed with several of the
      constructs. The mutant lacking a neck produced force at a somewhat reduced level,
      while the force exerted by the giraffe construct was higher than control. The
      single molecule displacement and force data support the hypothesis that the neck
      functions as a rigid lever, with the fulcrum for movement and force located at a
      point within the motor domain.

PMID- 10945997
TI  - cAMP-dependent protein kinase phosphorylation of EVL, a Mena/VASP relative,
      regulates its interaction with actin and SH3 domains.
AB  - Proteins of the Ena/VASP family are implicated in processes that require dynamic
      actin remodeling such as axon guidance and platelet activation. In this work, we
      explored some of the pathways that likely regulate actin dynamics in part via EVL
      (Ena/VASP-like protein). Two isoforms, EVL and EVL-I, were highly expressed in
      hematopoietic cells of thymus and spleen. In CD3-activated T-cells, EVL was found
      in F-actin-rich patches and at the distal tips of the microspikes that formed on
      the activated side of the T-cells. Like the other family members, EVL localized
      to focal adhesions and the leading edge of lamellipodia when expressed in
      fibroblasts. EVL was a substrate for the cAMP-dependent protein kinase, and this
      phosphorylation regulated several of the interactions between EVL and its
      ligands. Unlike VASP, EVL nucleated actin polymerization under physiological
      conditions, whereas phosphorylation of both EVL and VASP decreased their
      nucleating activity. EVL bound directly to the Abl, Lyn, and nSrc SH3 domains;
      the FE65 WW domain; and profilin, likely via its proline-rich core. Binding of
      Abl and nSrc SH3 domains, but not profilin or other SH3 domains, was abolished by
      cAMP-dependent protein kinase phosphorylation of EVL. We show strong cooperative
      binding of two profilin dimers on the polyproline sequence of EVL. Additionally,
      profilin competed with the SH3 domains for binding to partially overlapping
      binding sites. These data suggest that the function of EVL could be modulated in
      a complex manner by its interactions with multiple ligands and through
      phosphorylation by cyclic nucleotide dependent kinases.

PMID- 10945999
TI  - Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II
      transmembrane matrix metalloproteinase regulated by a single cleavage for both
      secretion and activation.
AB  - Matrix metalloproteinases characterized so far are either secreted or membrane
      anchored via a type I transmembrane domain or a glycosylphosphatidylinositol
      linkage. Lacking either membrane-anchoring mechanism, the newly discovered CA
      MMP/MMP-23 was reported to be expressed as a cell-associated protein. In this
      report, we present evidence that CA-MMP is expressed as an integral membrane
      zymogen with an N-terminal signal anchor, and secreted as a fully processed
      mature enzyme. We further demonstrate that L(20)GAALSGLCLLSALALL(36) is required
      for this unique membrane localization as a signal anchor and its secretion is
      regulated by a proprotein convertase motif RRRR(79) sandwiched between its pro-
      and catalytic domains. Thus, CA-MMP is a type II transmembrane MMP that can be
      regulated by a single proteolytic cleavage for both activation and secretion,
      establishing a novel paradigm for protein trafficking and processing within the
      secretory pathway.

PMID- 10946000
TI  - Patient mutations in doublecortin define a repeated tubulin-binding domain.
AB  - Doublecortin (DCX) missense mutations are found in two clusters in patients with
      defective cortical neuronal migration. Although DCX can function as a microtubule
      associated protein (MAP), the potential relationship between its MAP activity and
      neuronal migration is not understood. Here we show that the two clusters of
      patient mutations precisely define an internal tandem repeat. Each repeat alone
      binds tubulin, whereas neither repeat is sufficient for co-assembly with
      microtubules. The two tandem repeats are sufficient to mediate microtubule
      polymerization, and representative patient missense mutations lead to impaired
      polymerization both in vitro and in vivo as well as impaired microtubule
      stabilization. Furthermore, each repeat is predicted to have the secondary
      structure of a beta-grasp superfold motif, a motif not found in other MAPs. The
      patient mutations are predicted to disrupt the structure of the motif, suggesting
      that the motif may be critical for the DCX-tubulin interaction. These data
      provide both genetic and biochemical evidence that the interaction of DCX with
      microtubules is dependent upon this novel repeated tubulin-binding motif.

PMID- 10946001
TI  - Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human
      glucuronyltransferase I.
AB  - Human beta1,3-glucuronyltransferase I (GlcAT-I) is a central enzyme in the
      initial steps of proteoglycan synthesis. GlcAT-I transfers a glucuronic acid
      moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common
      linkage region trisaccharide Gal beta 1-3Gal beta 1-4Xyl covalently bound to a
      Ser residue at the glycosaminylglycan attachment site of proteoglycans. We have
      now determined the crystal structure of GlcAT-1 at 2.3 A in the presence of the
      donor substrate product UDP, the catalytic Mn(2+) ion, and the acceptor substrate
      analog Gal beta 1-3Gal beta 1-4Xyl. The enzyme is a alpha/beta protein with two
      subdomains that constitute the donor and acceptor substrate binding site. The
      active site residues lie in a cleft extending across both subdomains in which the
      trisaccharide molecule is oriented perpendicular to the UDP. Residues Glu(227),
      Asp(252), and Glu(281) dictate the binding orientation of the terminal Gal-2
      moiety. Residue Glu(281) is in position to function as a catalytic base by
      deprotonating the incoming 3-hydroxyl group of the acceptor. The conserved DXD
      motif (Asp(194), Asp(195), Asp(196)) has direct interaction with the ribose of
      the UDP molecule as well as with the Mn(2+) ion. The key residues involved in
      substrate binding and catalysis are conserved in the glucuronyltransferase family
      as well as other glycosyltransferases.

PMID- 10946003
TI  - 2000. Changes In management and publication

PMID- 10946002
TI  - In vivo quantification of parallel and bidirectional fluxes in the anaplerosis of
      Corynebacterium glutamicum.
AB  - The C(3)-C(4) metabolite interconversion at the anaplerotic node in many
      microorganisms involves a complex set of reactions. C(3) carboxylation to
      oxaloacetate can originate from phosphoenolpyruvate and pyruvate, and at the same
      time multiple C(4)-decarboxylating enzymes may be present. The functions of such
      parallel reactions are not yet fully understood. Using a (13)C NMR-based
      strategy, we here quantify the individual fluxes at the anaplerotic node of
      Corynebacterium glutamicum, which is an example of a bacterium possessing
      multiple carboxylation and decarboxylation reactions. C. glutamicum was grown
      with a (13)C-labeled glucose isotopomer mixture as the main carbon source and
      (13)C-labeled lactate as a cosubstrate. 58 isotopomers as well as 15 positional
      labels of biomass compounds were quantified. Applying a generally applicable
      mathematical model to include metabolite mass and carbon labeling balances, it is
      shown that pyruvate carboxylase contributed 91 +/- 7% to C(3) carboxylation. The
      total in vivo carboxylation rate of 1.28 +/- 0.14 mmol/g dry weight/h exceeds the
      demand of carboxylated metabolites for biosyntheses 3-fold. Excess oxaloacetate
      was recycled to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase. This
      shows that the reactions at the anaplerotic node might serve additional purposes
      other than only providing C(4) metabolites for biosynthesis.

PMID- 10946004
TI  - An appreciation of lewis I. Gidez and joan reilly, and welcome to virginia
      bourgeois

PMID- 10946005
TI  - Lysophosphatidylcholine-induced cellular injury in cultured fibroblasts involves
      oxidative events.
AB  - Lysophosphatidylcholine (lysoPC), formed during LDL oxidation and located within
      atherosclerotic plaques, induces numerous cellular responses, but via unknown
      mechanisms. Cellular events involved in sublethal lysoPC-induced injury were
      examined because these are relevant to mechanisms by which lysoPC alters cell
      behavior. LysoPC evoked transient membrane permeabilization in fibroblasts within
      10 min. Cells underwent reversible rounding within 2 h, returning 3 h later to
      grossly normal appearance and a normal response to growth stimulation. We asked
      whether this sublethal permeabilization resulted from physical perturbation of
      the plasma membrane or if it required cellular events. LysoPC induced leakage of
      fluorescent dye from unilamellar phospholipid vesicles, suggesting physical
      membrane perturbation was a significant contributor. To characterize this further
      we increased the cholesterol content of cells and vesicles to stabilize
      membranes, and found decreased lysoPC-induced permeabilization in both cell and
      cell-free systems as cholesterol levels increased. Interestingly, vitamin E, a
      known antioxidant, blunted lysoPC-induced permeabilization and morphological
      changes in cells. Thus, lysoPC appeared to cause an unexpected oxidant stress
      dependent enhancement of cell injury. To confirm this, several structurally
      distinct antioxidants, including N, N'-diphenyl-1,4-phenylenediamine, Desferal,
      Tiron, and 4-hydroxy TEMPO, were applied and these also were inhibitory. Oxidant
      stress was observed by a lysoPC-induced increase in fluorescence of 5- and 6
      carboxy-2',7'-dichlorodihydrofluorescein diacetate, an intracellular marker of
      reactive oxygen species. Lysophosphatidylethanolamine (lysoPE) caused
      qualitatively similar morphological changes to cells and induced
      permeabilization, but injury by lysoPE was not inhibited by antioxidants. These
      data suggest that generation of intracellular reactive oxygen species follows
      lysoPC-induced plasma membrane destabilization and that this lysoPC-specific
      oxidant stress enhances cell injury. This intracellular oxidant stress in
      response to lysoPC may be an integral part of the multiple influences lysoPC has
      on gene expression and cell function.

PMID- 10946006
TI  - Novel mutations in the microsomal triglyceride transfer protein gene causing
      abetalipoproteinemia.
AB  - Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual
      absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only
      limited numbers of families have been screened for mutations in the microsomal
      triglyceride transfer protein (MTP) gene. To clarify the genetic basis of
      clinical diversity of ABL, mutations of the MTP gene have been screened in 4
      unrelated patients with ABL. Three novel mutations have been identified: a
      frameshift mutation caused by a single adenine deletion at position 1389 of the
      cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice
      site mutation, 2218-2A-->G, in a compound heterozygous form. The frameshift and
      splice site mutations are predicted to encode truncated forms of MTP. When
      transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein
      disulfide isomerase (PDI) but displayed negligible MTP activity. It is of
      interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has
      none of the manifestations characteristic of classic ABL even though his plasma
      apoB and vitamin E were virtually undetectable. These results indicated that
      defects of the MTP gene are the proximal cause of ABL.

PMID- 10946007
TI  - Lipid peroxides induce expression of catalase in cultured vascular cells.
AB  - Various forms of oxidized low-density lipoproteins (Ox-LDL) are thought to play a
      major role in the development of atherosclerosis. The lipid components of Ox-LDL
      present a plethora of proatherogenic effects in in vitro cell culture systems,
      suggesting that oxidative stress could be an important risk factor for coronary
      artery disease. However, buried among these effects are those that could be
      interpreted as antiatherogenic. The present study demonstrates that various
      oxidants, including oxidized fatty acids and mildly oxidized forms of LDL (MO
      LDL), are able to induce catalase (an antioxidant enzyme) expression in rabbit
      femoral arterial smooth muscle cells (RFASMC), RAW cells (macrophages), and human
      umbilical vein endothelial cells (HUVEC). In RFASMC, catalase protein, mRNA, and
      the enzyme activity are increased in response to oxidized linoleic acid (13
      hydroperoxy-9,11-octadecadienoic acid [13-HPODE] and 13-hydroxy-9,11
      octadecadienoic acid [13-HODE]), MO-LDL, or hydrogen peroxide (H(2)O(2)). Such an
      increase in catalase gene expression cannot totally be attributed to the cellular
      response to an intracellular generation of H(2)O(2) after the addition of 13
      HPODE or 13-HODE because these agents induce a further increase of catalase as
      seen in catalase-transfected RFASMC. Taken together with the induction of heme
      oxygenase, NO synthase, manganese superoxide dismutase (Mn-SOD), and glutathione
      synthesis by oxidative stress, our results provide yet more evidence suggesting
      that a moderate oxidative stress can induce cellular antioxidant response in
      vascular cells, and thereby could be beneficial for preventing further oxidative
      stress.

PMID- 10946008
TI  - Phosphatidylinositol promotes cholesterol transport in vivo.
AB  - To examine the role that lipoprotein charge plays in cholesterol metabolism in
      vivo, we characterized the effects of an intravenous injection of 40 micromol of
      an uncharged phospholipid (phosphatidylcholine, PC) or an anionic phospholipid
      (phosphatidylinositol, PI) into fasted rabbits. PC injection had a negligible
      effect on lipoprotein charge and composition, similar to that observed in a
      saline-injected animal. In contrast, PI injection caused a significant increase
      in the net negative surface charge of all lipoproteins after only 10 min,
      followed by a gradual return to normal by 24 h. Lipoprotein compositional
      analysis showed that PI caused a significant increase of cholesteryl ester (CE)
      and cholesterol (FC) in the VLDL pool by 3 h, with no changes in VLDL
      triglyceride content. While the bulk of the plasma CE was located in the HDL pool
      in the PC-injected animals, in the PI animals, VLDL became the major CE storage
      compartment. No major changes in the levels or composition of HDL or LDL were
      evident over the 24-h turnover period. Co-injection of [(3)H]FC revealed a 30
      fold greater rate of clearance of the labeled cholesterol from the PI-injected
      rabbit plasma. In addition, the rate of cholesterol esterification by
      lecithin:cholesterol acyltransferase was almost completely inhibited in the PI
      animals. In summary, a bolus injection of PI into rabbits appears to enhance the
      mobilization of cellular sterol and promote a rapid clearance of both FC and CE
      from the plasma compartment. The data show that lipoprotein charge can affect
      cholesterol transport and that this process can be selectively manipulated.

PMID- 10946009
TI  - Purification, characterization, and cDNA sequencing of cytosolic phospholipase
      A(2) from equine neutrophils.
AB  - It has been demonstrated that equine neutrophils, but not eosinophils, require
      exogenous arachidonic acid for calcium ionophore A23187-induced leukotriene
      synthesis. Because cytosolic phospholipase A(2) (cPLA(2)) plays an essential role
      in leukotriene formation in leukocytes, we investigated the presence of a
      functional cPLA(2) in equine neutrophils. To determine whether cPLA(2) from
      neutrophils was catalytically active, we purified the enzyme >6,500 fold with 3%
      recovery from equine neutrophils. The full-length cDNA sequence encoded a 749
      amino acid protein. The deduced amino acid sequence demonstrated 95% identity
      with human and mouse cPLA(2), as well as 83 and 73% identity with chicken and
      zebra fish cPLA(2) protein, respectively. The equine cPLA(2) possessed some
      properties that distinguished the equine enzyme from the human enzyme. First, the
      enzyme activity of the equine cPLA(2) was differently influenced by cations as
      compared with the human cPLA(2). Second, the equine neutrophil cPLA(2) migrated
      as an approximately 105-kDa protein, in comparison with human cPLA(2) which
      migrated as a 110-kDa protein. A difference between equine neutrophils and
      eosinophils in the degree of phosphorylation of the cPLA(2) protein was observed.
      Thus, the cPLA(2) protein from eosinophils was constitutively phosphorylated,
      while the cPLA(2) protein from neutrophils was unphosphorylated. In summary,
      these results demonstrate that equine neutrophils indeed express an active
      cPLA(2) protein but that there is a difference in the degree of phosphorylation
      of the cPLA(2) protein between equine neutrophils and eosinophils. This
      difference might explain the difference between the two cell types in the
      capacity to produce leukotrienes from endogenous substrate.

PMID- 10946010
TI  - Plasma apolipoprotein L concentrations correlate with plasma triglycerides and
      cholesterol levels in normolipidemic, hyperlipidemic, and diabetic subjects.
AB  - Apolipoprotein L is a newly recognized component of human plasma lipoproteins.
      Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct
      HDL subpopulations. In an effort to gain inference as to its as yet unknown
      function, we studied biological determinants of apoL levels in human plasma. The
      distribution of apoL in normal subjects is asymmetric, with marked skewing toward
      higher values. No difference was found in apoL concentrations between males and
      females, but we observed an elevation of apoL in primary hypercholesterolemia
      (10.1 vs. 8.5 microgram/mL in control), in endogenous hypertriglyceridemia (13.8
      microgram/mL, P < 0.001), combined hyperlipidemia phenotype (18.7 g/mL, P <
      0.0001), and in patients with type II diabetes (16.2 microgram/mL, P < 0.02) who
      were hyperlipidemic. Significant positive correlations were observed between apoL
      and the log of plasma triglycerides in normolipidemia (0.446, P < 0.0001),
      endogenous hypertriglyceridemia (0.435, P < 0.01), primary hypercholesterolemia
      (0.66, P < 0.02), combined hyperlipidemia (0.396, P < 0.04), hypo
      alphalipoproteinemia (0.701, P < 0.005), and type II diabetes with hyperlipidemia
      (0.602, P < 0. 01). Apolipoprotein L levels were also correlated with total
      cholesterol in normolipidemia (0.257, P < 0.004), endogenous hypertriglyceridemia
      (0.446, P = 0.001), and non-insulin-dependent diabetes mellitus (NIDDM) (0.548, P
      < 0.02). No significant correlation was found between apoL and body mass index,
      age, sex, HDL-cholesterol or fasting glucose and glycohemoglobin levels. ApoL
      levels in plasma of patients with primary cholesteryl ester transfer protein
      deficiency significantly increased (7.1 +/- 0.5 vs. 5.47 +/- 0.27, P < 0.006).

PMID- 10946011
TI  - Kidney lipids in galactosylceramide synthase-deficient mice. Absence of
      galactosylsulfatide and compensatory increase in more polar sulfoglycolipids.
AB  - UDP-galactose:ceramide galactosyltransferase (CGT) catalyzes the final step in
      the synthesis of galactosylceramide (GalCer). It has previously been shown that
      CGT-deficient mice do not synthesize GalCer and its sulfated derivative GalCer
      I(3)-sulfate (galactosylsulfatide, SM4s) but form myelin containing
      glucosylceramide (GlcCer) and sphingomyelin with 2-hydroxy fatty acids. Because
      relatively high concentrations of GalCer and SM4s are present also in mammalian
      kidney, we analyzed the composition of lipids in the kidney of Cgt(-/-) and, as a
      control, Cgt(+/-) and wild-type mice. The homozygous mutant mice lacked GalCer,
      galabiaosylceramide (Ga(2)Cer), and SM4s. Yet, they did not show any major
      morphological or functional defects in the kidney. A slight increase in GlcCer
      containing 4-hydroxysphinganine was evident among neutral glycolipids.
      Intriguingly, more polar sulfoglycolipids, that is, lactosylceramide II(3)
      sulfate (SM3) and gangliotetraosylceramide II(3),IV(3)-bis-sulfate (SB1a), were
      expressed at 2 to 3 times the normal levels in Cgt(-/-) mice, indicating
      upregulation of biosynthesis of SB1a from GlcCer via SM3. Given that SM4s is a
      major polar glycolipid constituting renal tubular membrane, the increase in SM3
      and SB1a in the mice deficient in CGT and thus SM4s appears to be a compensatory
      process, which could partly restore kidney function in the knockout mice.

PMID- 10946012
TI  - Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese
      and obese humans.
AB  - Studies have shown evidence of production of nitric oxide (NO) in adipose tissue,
      as well as inhibition of lipolysis by NO. We have analyzed nitric oxide synthase
      (NOS) expression in subcutaneous adipose tissue from 13 nonobese and 18 obese
      male subjects. Using a competitive reverse transcription polymerase chain
      reaction method, endothelial (eNOS) and inducible (iNOS), but not neuronal
      (nNOS), nitric oxide synthase mRNA expression was detected in isolated fat cells
      and pieces of adipose tissue. Tissue mRNA levels for eNOS were 3,814 +/- 825 and
      5,956 +/- 476 amol/mg RNA (P = 0.043), and for iNOS 306 +/- 38 and 332 +/- 48
      amol/mg RNA, for nonobese and obese individuals, respectively. Western blotting
      revealed similar eNOS protein levels in isolated fat cells and adipose tissue
      pieces. Protein levels for eNOS in nonobese and obese individuals, respectively,
      were (in optical density [OD] units per mm(2) per 100 microgram of total protein)
      0.11 +/- 0.08 and 2.80 +/- 1.30 (P = 0.043). iNOS protein was detectable, but not
      measurable, at low levels in a subset of obese patients (3 of 10). iNOS protein
      levels could not be detected in nonobese individuals. Hormone-sensitive lipase
      (HSL), the key regulating enzyme in lipolysis, is reduced in obesity. The
      expression of HSL protein in subcutaneous adipose tissue was studied in the same
      subset of patients; in agreement with previous results, HSL levels were reduced
      in obese subjects: 4.64 +/- 1.10 and 1.27 +/- 0.35 (P = 0.012) in nonobese and
      obese subjects, respectively. In conclusion, this study shows that eNOS and iNOS,
      but not nNOS, are present in human subcutaneous adipose tissue. Gene expression
      and protein levels of eNOS are increased, whereas HSL protein levels are
      decreased in obesity. It is speculated that increased NO production, preferably
      by eNOS, and decreased HSL levels may cause decreased subcutaneous adipose tissue
      lipolysis in obesity. synthases in subcutaneous adipose tissue of nonobese and
      obese humans.

PMID- 10946013
TI  - Assay for the transbilayer distribution of glycolipids. Selective oxidation of
      glucosylceramide to glucuronylceramide by TEMPO nitroxyl radicals.
AB  - In the present study, 2,2,6,6-tetramethylpiperidinooxy nitroxide (TEMPO) has been
      applied successfully to discriminate between glucosylceramide in the outer and
      inner leaflets of closed membrane bilayers. The nitroxyl radicals TEMPO and
      carboxy-TEMPO, once oxidized to nitrosonium ions, are capable of oxidizing
      residues that contain primary hydroxyl and amino groups. When applied to
      radiolabeled glucosylceramide in liposomes, oxidation with TEMPO led to an
      oxidized product that was easily separated from the original lipid by thin-layer
      chromatography, and that was identified by mass spectrometric analysis as the
      corresponding acid glucuronylceramide. To test whether oxidation was confined to
      the external leaflet, TEMPO was applied to large unilamellar vesicles (LUVs)
      consisting of egg phosphatidylcholine- egg phosphatidylethanolamine;-cholesterol
      55:5:40 (mol/mol). TEMPO oxidized most radiolabeled phosphatidylethanolamine,
      whereas carboxy-TEMPO oxidized only half. Hydrolysis by phospholipase A(2)
      confirmed that 50% of the phosphatidylethanolamine was accessible in the external
      bilayer leaflet, suggesting that TEMPO penetrated the lipid bilayer and carboxy
      TEMPO did not. When applied to LUVs containing <1 mol% radiolabeled
      glucosylceramide or short-chain C(6)-glucosylceramide, carboxy-TEMPO oxidized
      half the glucosylceramide. However, if surface C(6)-glucosylceramide was first
      depleted by bovine serum albumin (BSA) (extracting 49 +/- 1%), 94% of the
      remaining C(6)-glucosylceramide was resistant to oxidation. Carboxy-TEMPO
      oxidized glucosylceramide on the surface of LUVs without affecting inner leaflet
      glucosylceramide. At pH 9.5 and at 0 degrees C, the reaction reached completion
      by 20 min.

PMID- 10946014
TI  - Phospholipid composition of reconstituted high density lipoproteins influences
      their ability to inhibit endothelial cell adhesion molecule expression.
AB  - The ability of different phosphatidylcholine (PC) species to inhibit cytokine
      induced expression of vascular cell adhesion molecule 1 (VCAM-1) in human
      umbilical vein endothelial cells (HUVECs) was investigated. PC species containing
      palmitoyl- in the sn-1 position and palmitoyl- (DPPC), arachidonyl- (PAPC),
      linoleoyl- (PLPC) or oleoyl- (POPC) in the sn-2 position were compared. These PC
      species were studied as components of reconstituted high density lipoproteins
      (rHDL) (containing apolipoprotein A-I [apoA-I] as the sole protein) or as small
      unilamellar vesicles (SUVs). The rHDL containing PLPC and PAPC inhibited VCAM-1
      expression in activated HUVECs by 95 and 70%, respectively, at an apoA-I
      concentration of 16 micrometer. At this concentration of apoA-I, POPC rHDL
      inhibited by only 16% and DPPC rHDL did not inhibit at all. These differences
      could not be explained by differential binding of the rHDL to HUVECs. The same
      hierarchy of inhibitory activity was observed when these PC species were
      presented to the cells as SUVs but only when the SUVs also contained an
      antioxidant. It was concluded that rHDL PC is responsible for their inhibitory
      activity and that this varies widely with different PC species.

PMID- 10946015
TI  - Lipoprotein deprivation stimulates transcription of the CTP:phosphocholine
      cytidylyltransferase gene.
AB  - We examined the effect of lipoprotein deprivation on the expression of the rate
      regulatory enzyme involved in phosphatidylcholine (PtdCho) synthesis,
      phosphocholine cytidylyltransferase (CCT), within an alveolar type II epithelial
      cell line (MLE-12). Compared with cells exposed to 10% fetal bovine serum (FBS,
      control), cells cultured with lipoprotein-deficient serum (LPDS) for 72 h had a
      150% increase in CCT activity. Stimulation of CCT activity after LPDS exposure
      was associated with a 2-fold increase in immunoreactive CCT content and a
      corresponding increase in [(35)S]methionine incorporation into newly synthesized
      CCT. LPDS induction of CCT protein was reversible, as it was suppressed to
      baseline levels by the addition of low density lipoproteins to the culture
      medium. Northern blotting revealed that LPDS increased CCT mRNA levels 2-fold
      compared with control. The induction of CCT mRNA by LPDS was not associated with
      an increase in mRNA half-life. Nuclear run-on assays revealed that LPDS-induced
      expression of CCT was due, at least in part, to an increase in gene
      transcription. These studies reveal that lipoprotein deprivation upregulates the
      activity of a key enzyme involved in the PtdCho biosynthetic pathway. LPDS
      induction of CCT protein might serve as a novel compensatory mechanism in
      response to lipid deprivation by increasing cellular transcription of the CCT
      gene.

PMID- 10946016
TI  - Centripetal cholesterol flow from the extrahepatic organs through the liver is
      normal in mice with mutated Niemann-Pick type C protein (NPC1).
AB  - Niemann-Pick type C (NPC) protein functions to move unesterified cholesterol from
      the lysosomal compartment to other intracellular sites for further metabolism
      and/or excretion. This cholesterol is brought into the cell through the coated
      pit pathway and accumulates in the lysosomes when NPC protein is mutated. The
      present study quantitated the alternative uptake process that brings cholesterol
      into the cell through the scavenger receptor, class B, type I (SR-BI) pathway in
      animals with this mutation. In homozygous NPC mice, the tissues of the
      extrahepatic compartment accumulated an excess of 14 mg of cholesterol each day
      per kg body weight, and synthesis increased by a similar amount (to 111 mg/day
      per kg) to compensate for this functional loss of sterol through lysosomal
      sequestration. An amount of cholesterol (108 mg/day per kg) nearly equal to that
      synthesized in the extrahepatic compartment was carried through the circulation
      by high density lipoprotein (HDL) and taken up by the liver. The rate of hepatic
      cholesterol excretion from the NPC mice as fecal acidic (65 mg/day per kg) and
      neutral (85 mg/day per kg) sterols was elevated 61% above control values and was
      accounted for by the total amount of cholesterol brought to the liver in HDL and
      synthesized in the hepatocytes. These studies demonstrated that while cholesterol
      entering tissues of the NPC animals through the coated-pit pathway became
      sequestered in the lysosomal compartment and was metabolically inactive,
      cholesterol that was newly synthesized or that entered cells through the SR-BI
      pathway was metabolized and excreted normally.

PMID- 10946017
TI  - Low levels of high density lipoproteins in Turks, a population with elevated
      hepatic lipase. High density lipoprotein characterization and gender-specific
      effects of apolipoprotein e genotype.
AB  - Turks have strikingly low levels of high density lipoprotein cholesterol (HDL-C)
      (10-15 mg/dL lower than those of Americans or Western Europeans) associated with
      elevated hepatic lipase mass and activity. Here we report that Turks have low
      levels of high density lipoprotein subclass 2 (HDL(2)), apoA-I-containing
      lipoproteins (LpA-I), and pre-beta-1 HDL and increased levels of HDL(3) and LpA
      I/A-II particles (potentially an atherogenic lipid profile). The frequency
      distributions of HDL-C and LpA-I levels were skewed toward bimodality in Turkish
      women but were unimodal in Turkish men. The apoE genotype affected HDL-C and LpA
      I levels in women only. In women, but not men, the varepsilon2 allele was
      strikingly more prevalent in those with the highest levels of HDL-C and LpA-I
      than in those with the lowest levels. The higher prevalence of the epsilon2
      allele in these subgroups of women was not explained by plasma triglyceride
      levels, total cholesterol levels, age, or body mass index. The modulating effects
      of apoE isoforms on lipolytic hydrolysis of HDL by hepatic lipase (apoE2
      preventing efficient hydrolysis) or on lipoprotein receptor binding (apoE2
      interacting poorly with the low density lipoprotein receptors) may account for
      differences in HDL-C levels in Turkish women (the epsilon2 allele being
      associated with higher HDL levels). In Turkish men, who have substantially higher
      levels of hepatic lipase activity than women, the modulating effect of apoE may
      be overwhelmed. The gender-specific impact of the apoE genotype on HDL-C and LpA
      I levels in association with elevated levels of hepatic lipase provides new
      insights into the metabolism of HDL.

PMID- 10946018
TI  - Sib-pair linkage analysis of longitudinal changes in lipoprotein risk factors and
      lipase genes in women twins.
AB  - Based on longitudinal twin data in women, we have previously demonstrated a
      genetic influence on changes in lipoprotein risk factors, blood pressure
      measurements, and body mass index over a decade. The present study examined the
      linkage between changes in lipoprotein variables and candidate genes encoding the
      hormone-sensitive lipase (HSL), hepatic lipase (HL), and lipoprotein lipase
      (LPL). The sample consisted of 126 dizygotic (DZ) pairs of women twins who
      participated in the two examinations of the Kaiser Permanente Women Twins Study,
      performed a decade apart. Using quantitative sib-pair linkage analysis, a linkage
      was demonstrated between the locus for hormone-sensitive lipase and age-adjusted
      changes in plasma triglyceride (P = 0.015), which became more significant after
      adjustment for environmental factors and the exam-1 level (P = 0.005). There was
      also evidence suggesting linkage between the locus for hepatic lipase and changes
      in triglyceride (P = 0.023), but no linkage was detected for lipoprotein lipase
      and changes of lipid levels with time. These findings suggest that variation at
      these candidate gene loci may underlie a portion of the intraindividual
      variations in these coronary heart disease (CHD) risk factors, and that studies
      to identify the functional variants could provide new insights into genetic
      susceptibility to cardiovascular disease.

PMID- 10946019
TI  - Differential regulation of the stearoyl-CoA desaturase genes by
      thiazolidinediones in 3T3-L1 adipocytes.
AB  - Two stearoyl-CoA desaturase (SCD) isoforms can be expressed during the
      differentiation of 3T3-L1 preadipocytes into adipocytes. Here we report on the
      effects of the peroxisome proliferator-activated receptor gamma ligand
      troglitazone (TRO) on scd1 and scd2 mRNA levels as determined by Northern
      blotting, on SCD protein expression as determined by Western blotting, and on
      total lipid composition as determined by GC during differentiation. In
      preadipocytes, scd1 mRNA and SCD protein were not detected, whereas scd2 mRNA was
      detected. These cells have high levels of palmitate (16:0), stearate (18:0), and
      monounsaturated oleate (Delta(9)-18:1) and low levels of monounsaturated
      palmitoleate (Delta(9)-16:1). In MDI (methylisobutylxanthine, dexamethasone, and
      insulin)-treated cells, scd1 mRNA and SCD protein were increased approximately
      100-fold relative to preadipocyte levels, the scd2 mRNA level was increased 2
      fold, Delta(9)-16:1 was increased approximately 20-fold, and 18:0 was decreased
      approximately 3-fold. In TRO-treated cells, the scd1 mRNA level was lower than
      that observed in preadipocytes, while the scd2 mRNA level was similar. TRO also
      decreased scd1 mRNA in primary adipocytes. The TRO-treated cells contained a
      Delta(9)-18:1 level typical of MDI-treated cells whereas, conversely, these cells
      also contained a low Delta(9)-16:1 level typical of preadipocytes. The
      implications of these correlations for the regulatory and enzymatic mechanism(s)
      used to establish and maintain lipid composition are discussed.

PMID- 10946020
TI  - Lipid and apolipoprotein concentrations in prenodal leg lymph of fasted humans.
      Associations with plasma concentrations in normal subjects, lipoprotein lipase
      deficiency, and LCAT deficiency.
AB  - The extent to which lipid and apolipoprotein (apo) concentrations in tissue
      fluids are determined by those in plasma in normal humans is not known, as all
      studies to date have been performed on small numbers of subjects, often with
      dyslipidemia or lymphedema. Therefore, we quantified lipids, apolipoproteins,
      high density lipoprotein (HDL) lipids, and non-HDL lipids in prenodal leg lymph
      from 37 fasted ambulant healthy men. Lymph contained almost no triglycerides, but
      had higher concentrations of free glycerol than plasma. Unesterified cholesterol
      (UC), cholesteryl ester (CE), phosphatidylcholine (PC), and sphingomyelin (SPM)
      concentrations in whole lymph were not significantly correlated with those in
      plasma. HDL lipids, but not non-HDL lipids, were directly related to those in
      plasma. Lymph HDLs were enriched in UC. However, as the HDL cholesterol/non-HDL
      cholesterol ratio in lymph exceeded that in plasma, whole lymph nevertheless had
      a lower UC/CE ratio than plasma. Lymph also had a significantly higher SPM/PC
      ratio. The lymph/plasma (L/P) ratios of apolipoproteins were as follows: A-IV > A
      I and A-II > C-III and E > B. Comparison with the L/P ratios of seven
      nonlipoprotein proteins suggested that apoA-IV was predominantly lipid free.
      Concentrations of apolipoproteins A-II, A-IV, C-III, and E in lymph, but not of
      apolipoproteins A-I or B, were positively correlated with those in plasma. The
      L/P ratios of apolipoproteins B, C-III, and E in two subjects with lipoprotein
      lipase (LPL) deficiency, and of apolipoproteins A-I and A-IV in a subject with
      lecithin:cholesterol acyltransferase (LCAT) deficiency, were low relative to
      those in normal subjects. Thus, the concentrations of lipids, apolipoproteins,
      and lipoproteins in human tissue fluid are determined only in part by their
      concentrations in plasma. Other factors, including the actions of LPL and LCAT,
      are at least as important.

PMID- 10946021
TI  - Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice
      induces features of familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is a common inherited hyperlipidemia and
      a major risk factor for atherothrombotic cardiovascular disease. The cause(s)
      leading to FCHL are largely unknown, but the existence of unidentified "major"
      genes that would increase VLDL production and of "modifier" genes that would
      influence the phenotype of the disease has been proposed. Expression of
      apolipoprotein A-II (apoA-II), a high density lipoprotein (HDL) of unknown
      function, in transgenic mice produced increased concentration of apoB-containing
      lipoproteins and decreased HDL. Here we show that expression of human apoA-II in
      apoE-deficient mice induces a dose-dependent increase in VLDL, resulting in
      plasma triglyceride elevations of up to 24-fold in a mouse line that has 2-fold
      the concentration of human apoA-II of normolipidemic humans, as well as other
      well-known characteristics of FCHL: increased concentrations of cholesterol,
      triglyceride, and apoB in very low density lipoprotein (VLDL), intermediate
      density lipoprotein (IDL) and low density lipoprotein (LDL), reduced HDL
      cholesterol, normal lipoprotein lipase and hepatic lipase activities, increased
      production of VLDL triglycerides, and increased susceptibility to
      atherosclerosis. However, FCHL patients do not have plasma concentrations of
      human apoA-II as high as those of apoE-deficient mice overexpressing human apoA
      II, and the apoA-II gene has not been linked to FCHL in genome-wide scans.
      Therefore, the apoA-II gene could be a "modifier" FCHL gene influencing the
      phenotype of the disease in some individuals through unkown mechanisms including
      an action on a "major" FCHL gene. We conclude that apoE-deficient mice
      overexpressing human apoA-II constitute useful animal models with which to study
      the mechanisms leading to overproduction of VLDL, and that apoA-II may function
      to regulate VLDL production.

PMID- 10946022
TI  - Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is caused by deficient Delta(7)
      dehydrocholesterol reductase, which catalyzes the final step of the cholesterol
      biosynthetic pathway, resulting in low cholesterol and high concentrations of its
      direct precursors 7-dehydrocholesterol (7DHC) and 8DHC. We hypothesized that i)
      7DHC and 8DHC accumulation contributes to the poor outcome of SLOS patients and
      ii) blood exchange transfusions with hydroxymethylglutaryl (HMG)-CoA reductase
      inhibition would improve the precursor-to-cholesterol ratio and may improve the
      clinical outcome of SLO patients. First, an in vitro study was performed to study
      sterol exchange between plasma and erythrocyte membranes. Second, several
      exchange transfusions were carried out in vivo in two SLOS patients. Third,
      simvastatin was given for 23 and 14 months to two patients. The in vitro results
      illustrated rapid sterol exchange between plasma and erythrocyte membranes. The
      effect of exchange transfusion was impressive and prompt but the effect on plasma
      sterol levels lasted only for 3 days. In contrast, simvastatin treatment for
      several months demonstrated a lasting improvement of the precursor-to-cholesterol
      ratio in plasma, erythrocyte membranes, and cerebrospinal fluid (CSF). Plasma
      precursor concentrations decreased to 28 and 33% of the initial level,
      respectively, whereas the cholesterol concentration normalized by a more than
      twofold increase. During the follow-up period all morphometric parameters
      improved. The therapy was well tolerated and no unwanted clinical side effects
      occurred. This is the first study in which the blood cholesterol level in SLOS
      patients is normalized with a simultaneous significant decrease in precursor
      levels. There was a lasting biochemical improvement with encouraging clinical
      improvement. Statin therapy is a promising novel approach in SLOS that deserves
      further studies in larger series of patients.

PMID- 10946023
TI  - In nonhepatic cells, cholesterol 7alpha-hydroxylase induces the expression of
      genes regulating cholesterol biosynthesis, efflux, and homeostasis.
AB  - CHO cells expressing the liver-specific gene product cholesterol-7alpha
      hydroxylase showed a 6-fold increase in the biosynthesis of [(14)C]cholesterol
      from [(14)C]acetate, as well as increased enzymatic activities of 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase and squalene synthase. Cells
      expressing cholesterol-7alpha-hydroxylase contained less sterol response element
      binding protein 1 (SREBP1) precursor, whereas the cellular content of mature
      SREBP1, as well as the mRNAs of cholesterol biosynthetic genes (HMG-CoA reductase
      and squalene synthase), were all increased approximately 3-fold. Cells expressing
      cholesterol-7alpha-hydroxylase displayed greater activities of luciferase
      reporters containing the SREBP-dependent promoter elements derived from HMG-CoA
      reductase and farnesyl diphosphate synthase, in spite of accumulating
      significantly more free and esterified cholesterol and 7alpha-hydroxycholesterol.
      While cells expressing cholesterol-7alpha-hydroxylase displayed increased SREBP
      dependent transcription, sterol-mediated repression of SREBP-dependent
      transcription by LDL-cholesterol and exogenous oxysterols was similar in both
      cell types. Cells expressing cholesterol-7alpha-hydroxylase displayed greater
      rates of secretion of cholesterol as well as increased expression of the ABC1
      cassette protein mRNA. Adding 25-hydroxycholesterol to the culture medium of both
      cell types increased the expression of ABC1 cassette protein mRNA. The combined
      data suggest that in nonhepatic CHO cells multiple regulatory processes sensitive
      to cellular sterols act independently to coordinately maintain cellular
      cholesterol homeostasis.

PMID- 10946024
TI  - Effect of labeling of plasma lipoproteins with [(3)H]cholesterol on values of
      esterification rate of cholesterol in apolipoprotein B-depleted plasma.
AB  - The fractional esterification rate of cholesterol in apolipoprotein B (apoB)
      depleted plasma (FER(HDL)) is a good indicator of particle size distribution in
      high density lipoprotein (HDL) and low density lipoprotein (LDL). However, there
      has been a discrepancy in the absolute values of FER(HDL) published by different
      laboratories. Because the main difference between the methods was in the labeling
      of lipoproteins with [(3)H]cholesterol we investigated the effect of using
      Corning immunoplates and paper discs as carriers of the labeled unesterified
      cholesterol. We found that Corning plates trap some (3)H-labeled free
      cholesterol, which is released during incubation at 37 degrees C. This means that
      this additional (3)H-labeled free cholesterol is exposed to lecithin: cholesterol
      acyltransferase (LCAT) for a shorter time and artificially decreases FER(HDL).
      Using paper discs discarded before incubation as carriers of the (3)H-labeled
      free cholesterol results in complete labeling of HDL and thus yields higher
      values of FER(HDL).

PMID- 10946025
TI  - A sandwich enzyme-linked immunosorbent assay for human serum paraoxonase
      concentration.
AB  - Serum paraoxonase (PON) is associated with plasma high density lipoproteins, and
      prevents the oxidative modification of low density lipoproteins. We have
      developed a sensitive sandwich enzyme-linked immunosorbent assay (ELISA), using
      two monoclonal antibodies against PON, to measure serum PON concentration. The
      concentration of PON in healthy Japanese subjects was 59.3 +/- 1.3 microgram/mL
      (mean +/- SEM; n = 87). Serum PON concentrations in relation to the PON 192
      genetic polymorphism were: 69.5 +/- 2.9 microgram/mL in the QQ genotype; 63.0 +/-
      1.9 microgram/mL in the QR genotype; and 52.8 +/- 1.7 microgram/mL in the RR
      genotype. Concentrations were significantly lower in the RR than in the QQ
      genotype (P < 0.01). Serum paraoxonase specific activity was higher in RR than in
      QQ subjects (18.6 +/- 0.40 vs. 2. 56 +/- 0.05 nmol/min/microgram, P < 0.01), but
      arylesterase specific activity was unrelated to genotype. PON concentration was
      positively associated (P < 0.001) with both serum arylesterase activity and,
      after adjusting for the effect of the position 192 polymorphism, with serum
      paraoxonase activity. Subjects with angiographically verified coronary heart
      disease had significantly lower PON concentrations than the healthy controls
      (52.0 +/- 2.3 microgram/mL; n = 35, P < 0.01). This association was independent
      of the position 192 genotype. Our new ELISA should be of value for epidemiologic
      and clinical studies of serum PON concentration. immunosorbent assay for human
      serum paraoxonase concentration.

PMID- 10946026
TI  - Comparison of low-dose dobutamine ventriculography with low-dose dobutamine
      echocardiography for predicting regional improvement in left ventricular function
      after coronary artery bypass grafting.
AB  - The demonstration of a contractile reserve during low-dose dobutamine
      echocardiography (LDDE) identifies viable myocardium and predicts recovery of
      left ventricular (LV) function after myocardial revascularization in patients
      with chronic coronary artery disease. However, a technically difficult
      transthoracic visualization may limit the use of LDDE, thus requiring an
      alternative diagnostic procedure. The present study compares LDDE with low-dose
      dobutamine ventriculography (LDDV) in predicting an improvement in regional LV
      function after surgical revascularization. We studied 18 patients with coronary
      artery disease and LV dysfunction who were to undergo coronary artery bypass
      grafting. Preoperatively, all patients were evaluated for the presence of viable
      myocardium using LDDE and LDDV. Follow-up echocardiography at rest and left
      ventriculography were performed 4 months after successful revascularization to
      assess recovery of LV function. The sensitivity and specificity of LDDE to
      identify dysfunctional segments capable of recovering function were 63% and 71%,
      respectively, with a diagnostic accuracy of 68%. The sensitivity, specificity,
      and diagnostic accuracy of LDDE improved to 81%, 72%, and 76% when patients with
      optimal transthoracic evaluation were selected, whereas they were 30%, 77%, and
      57%, respectively, in those who underwent suboptimal evaluation. The sensitivity,
      specificity, and diagnostic accuracy of LDDV were 66%, 75%, and 71%,
      respectively, with no difference in subgroups of patients. This study
      demonstrates that LDDV can be considered a useful technique for identifying the
      presence of myocardial viability and may provide an advantage over LDDE in
      patients with suboptimal echocardiographic visualization.

PMID- 10946027
TI  - Angiographic and clinical outcome of mild to moderate nonocclusive unstented
      coronary artery dissection and the influence on coronary flow velocity reserve.
      The Debate I Study Group.
AB  - Limited data are available regarding the angiographic healing rate and
      physiologic impact of coronary artery dissections. Therefore, we studied the
      impact of coronary dissections on coronary flow velocity and outcome as well as
      their healing rate at 6-month follow-up balloon angioplasty. Of 297 patients who
      underwent balloon angioplasty, 225 underwent intracoronary Doppler measurements
      and 184 had Doppler and angiographic assessment at 6-month follow-up. Dissections
      were scored by an independent core lab (Cardialysis BV) and divided in 4 groups:
      mild (types A to B), moderate (type C), severe (D to F), and patients without
      dissections. Severe dissections (types D to F) were excluded from the analysis.
      Clinical, angiographic, and Doppler data were compared among the remaining 3
      patient groups. From the 67 dissections detected after balloon angioplasty, only
      3 (4.5%) remained unhealed at follow-up. Immediately after balloon angioplasty,
      the moderate dissection group was associated with a lower coronary flow velocity
      reserve than the patients with mild (2.16 +/- 0.60 vs 2.82 +/- 1.00, p = 0.037)
      or no dissections (2.16 +/- 0.60 vs 2.71 +/- 0.88, p = 0.046), respectively. In
      addition, higher recurrence of angina at 30 days was observed in the moderate
      group rather than in the mild group (5 [50%] vs 8 [16%], p = 0.0160) and in the
      patients without dissections (11 [12%], p = 0.007). After standard balloon
      angioplasty, the occurrence of unhealed dissections is a rare phenomenon. An
      impaired coronary flow reserve was observed after the development of nonocclusive
      type C dissections, which was associated with a worse short-term outcome.

PMID- 10946028
TI  - Effect of prior exposure to Chlamydia pneumoniae, Helicobacter pylori, or
      cytomegalovirus on the degree of inflammation and one-year prognosis of patients
      with unstable angina pectoris or non-Q-wave acute myocardial infarction.
AB  - Inflammation and chronic infections may be important features in the pathogenesis
      of acute coronary syndromes. We describe 6 systemic markers of inflammation in
      patients with unstable angina or non-Q-wave myocardial infarction and the
      relations between these markers, seropositivity to chronic infections, and
      prognosis. C-reactive protein (CRP), serum amyloid A protein (SAA), fibrinogen,
      interleukin-6 (IL-6), neopterin, procalcitonin, and serum antibody levels to
      Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus were measured on
      admission and 48 hours later. One-year clinical follow-up was performed. Plasma
      levels of acute phase reactants were all elevated on admission and increased
      further at 48 hours: CRP from 10.1 +/- 2.1 mg/L at baseline to 26.6 +/- 5.1 mg/L
      at 48 hours (p <0.001); SAA from 27.3 +/- 8.5 to 93.1 +/- 23.2 mg/dl (p <0.005);
      fibrinogen from 3.2 +/- 0.1 to 3.8 +/- 0.1 g/L (p <0.0001); whereas initial high
      levels of IL-6 tended also to increase from 9.8 +/- 2 to 15.3 +/- 3.1 pg/ml (p =
      NS). In contrast, neopterin and procalcitonin remained unchanged. We found no
      association between levels of each inflammatory marker and the serologic status.
      Furthermore, levels of inflammatory proteins in patients seronegative to all 3
      agents were comparable to those of patients seropositive to 2 or 3 infectious
      agents. The composite end points of death, myocardial infarction, recurrent
      angina, or revascularization at 1-year follow-up did not differ according to the
      serologic status. Thus, in patients with acute coronary syndromes, the acute
      phase proteins increased over the first 2 days of hospitalization. This initial
      inflammatory reaction as well as the 1-year clinical outcome did not differ
      according to the initial serologic status of Chlamydia pneumoniae, Helicobacter
      pylori, or cytomegalovirus.

PMID- 10946029
TI  - Heparin-coated Wiktor stents in human coronary arteries (MENTOR trial). MENTOR
      Trial Investigators.
AB  - The purpose of this study was to determine the feasibility, safety, and efficacy
      of elective stenting with heparin-coated Wiktor stents in patients with coronary
      artery disease. In experimental studies, heparin coating has been shown to
      prevent subacute thrombosis and restenosis. Recently, a new method of heparin
      coating was developed, resulting in a more stable and predictable heparin layer
      on stent devices. This trial constitutes the first in-human use of this coating
      procedure, applied on the well-known Wiktor stent device. Heparin-coated Wiktor
      stent implantation was performed in 132 consecutive patients (132 lesions) in a
      multicenter international trial from September 1996 to February 1997. Forty-three
      percent of patients had unstable angina, 33% had previous myocardial infarction,
      and 10% had diabetes mellitus. Patients were followed for 12 months for
      occurrence of major adverse cardiovascular events, and 96% of the eligible
      patients underwent quantitative angiographic control at 6 months. Stent
      deployment was successful in 95.5% of lesions. Minimal lumen diameter increased
      by 1.67 +/- 0.48 mm (from 1.02 +/- 0.38 mm before to 2.69 +/- 0.37 mm after the
      stent implantation). Mean percent diameter stenosis decreased from 67.4 +/- 11.3%
      before to 18.9 +/- 7.7% after the intervention. A successful intervention (<50%
      diameter stenosis and no major adverse cardiac events within 30 days) occurred in
      97% of the patients. The subacute thrombosis rate was 0.8%, which compares
      favorably with historical controls of this stent, and a low incidence of
      postprocedural increase in creatine kinase-MB was noted. At 6 months, event-free
      survival was 85% and angiographic restenosis rate was 22% with late loss of 0.78
      +/- 0.69 mm and a loss index of 0.48 +/- 0.44. Heparin-coated Wiktor stents
      appeared to be an efficacious device to treat Benestent-like lesions, yielding
      angiographic and clinical results comparable to a heparin-coated Palmaz-Schatz
      stent. Despite its use in more complex lesions, the incidence of subacute
      thrombosis appeared to be lower than historical controls with a similar noncoated
      stent.

PMID- 10946030
TI  - Six-month outcome after excimer laser coronary angioplasty for diffuse in-stent
      restenosis in native coronary arteries.
AB  - This study evaluated the intermediate-term follow-up after excimer laser coronary
      angioplasty (ELCA) and adjunctive percutaneous transluminal coronary angioplasty
      (PTCA) in patients with diffuse in-stent restenosis (lesion length >10 mm).
      Clinical and angiographic follow-up were performed at 6 months. Quantitative
      coronary angiography performed at 3 stages-during stent implantation, before and
      after ELCA + PTCA, and at follow-up-included measurements of the minimum lumen
      diameter (MLD) and percent diameter stenosis (DS). Sixteen consecutive patients
      were included. The (median + range) stent length was 36 mm (range 15 to 105),
      with a restenotic lesion length of 32 mm (range 10 to 90). After ELCA + PTCA, the
      MLD increased from 0.60 +/- 0.41 to 2.28 +/- 0.50 mm, whereas the DS decreased
      from 76 +/- 16% to 22 +/- 8%. Despite adjunctive high-pressure PTCA, the MLD
      after ELCA + PTCA remained smaller than the MLD after initial stent implantation,
      (2.28 +/- 0. 50 mm vs 2.67 +/- 0.32 mm, p = 0.014). Adverse events included ELCA
      related acute coronary occlusion in 4 patients and a per-procedural intracerebral
      hematoma in 1. At 6 months, there was recurrence of angina in all patients.
      Angiographic follow-up was completed in 13 patients (87%), showing a reocclusion
      in 6 (46%), a >50% DS in 6 (MLD 1.03 +/- 0.87 mm, DS 68 +/- 24%), and a distal de
      novo lesion in 1. Despite satisfactory acute angiographic results, the recurrence
      of significant restenosis in all patients suggests that ELCA + PTCA is not a
      suitable stand-alone therapy for diffuse in-stent restenosis of long stented
      segments.

PMID- 10946031
TI  - Outcome of coronary revascularization in patients on renal dialysis.
AB  - Previous retrospective studies showed high periprocedure mortality rate and poor
      outcome after percutaneous transluminal coronary angioplasty (PTCA) or coronary
      artery bypass grafting (CABG) among renal dialysis patients. The purpose of this
      study was to compare mortality and clinical event rates in renal dialysis
      patients after PTCA or CABG. We identified 252 patients from the Emory
      Cardiovascular Database who were on dialysis and who received PTCA (122 patients)
      or CABG (130 patients) at Emory University Hospital and Crawford W. Long Hospital
      between March 1987 and December 1997. Baseline and angiographic characteristics,
      in-hospital, and 1-year outcome were compared between the 2 groups. Left main
      disease and 3-vessel coronary artery disease were significantly more common in
      the CABG group. There was a higher periprocedure and in-hospital mortality in the
      CABG group (6.9% vs 1.6%, p = 0.04). Patients in the PTCA group underwent repeat
      revascularization 11 times more frequently within 1 year (22% vs 2%). At 1 year,
      mortality was 23% in the PTCA group and 27% in the CABG group, with no
      statistical difference between the 2 groups. This nonrandomized comparison
      reveals that PTCA and CABG can be performed in selected renal dialysis patients
      with an acceptable in-hospital major complication rate; however, 1-year mortality
      remains high in dialysis patients after coronary revascularization. Therefore,
      attempts at improving outcome in dialysis patients should focus on the prevention
      and treatment of coronary artery disease before they require coronary
      revascularization.

PMID- 10946032
TI  - Reappraising the role of immediate intervention following thrombolytic
      recanalization in acute myocardial infarction.
AB  - Early studies indicated that after successful thrombolytic recanalization,
      adjunctive percutaneous transluminal coronary angioplasty (PTCA) was not
      appropriate, even when a significant residual stenosis was present. The aim of
      this study was to assess in-hospital clinical outcomes of patients with acute
      myocardial infarction (AMI) who underwent successful recanalization after
      thrombolytic therapy. The relation between repeat AMI/unstable angina and the
      severity of the stenosis, as well as other angiographic and clinical features was
      also examined. One hundred patients with AMI of <10 hours underwent coronary
      angiography 2 hours after receiving thrombolytic therapy. Salvage PTCA +/-
      stenting was performed if recanalization was unsuccessful (Thrombolysis In
      Myocardial Infarction [TIMI] trial grade 0 to 2), and no PTCA was undertaken if
      there was brisk anterograde flow (TIMI 3). Angiographic analysis was performed to
      assess the severity of the residual lesion, as well as the presence or absence of
      thrombus. Forty patients had unsuccessful recanalization, and of these, 36
      underwent attempted PTCA. Of the 60 patients with TIMI 3 flow, 15 required repeat
      angiography and PTCA after repeat AMI (n = 13) or unstable angina (n = 2) within
      5 days. Receiver-operating characteristic analysis indicated an optimum percent
      diameter stenosis predictor of 85% for repeat AMI/unstable angina. There was no
      additional relation to age, gender, time to thrombolysis, the infarct-related
      artery, or the presence of culprit lesion thrombus. After recanalization, a high
      grade stenosis >85% is common (n = 25, 42.4%). This is associated with a 54%
      repeat AMI/unstable angina risk-a ninefold increase in the incidence of such
      events than in patients with lesions <85%. Thus, patients with narrowings >85%
      may benefit from early intervention rather than a conservative approach.
      Narrowings <85% have a 94% probability of no repeat AMI/unstable angina and do
      not require early intervention.

PMID- 10946033
TI  - Effects of simvastatin (40 and 80 mg/day) in patients with mixed hyperlipidemia.
AB  - Mixed hyperlipidemia is characterized by both elevated total cholesterol and
      triglycerides. It is estimated to account for 10% to 20% of patients with
      dyslipidemia. This study assessed the lipid-altering efficacy and tolerability of
      simvastatin 40 and 80 mg/day as monotherapy. One hundred thirty patients (62
      women [48%], 24 [16%] with type 2 diabetes mellitus, mean age 53 years) with
      mixed hyperlipidemia (baseline low-density lipoprotein [LDL] cholesterol 156
      mg/dl [mean], and triglycerides 391 mg/dl [median) were randomized in a
      multicenter, double-masked, placebo-controlled, 3-period, 22-week, balanced
      crossover study, and received placebo, and simvastatin 40 and 80 mg/day each for
      6 weeks. Compared with placebo, simvastatin produced significant (p <0.01) and
      dose-dependent changes in all lipid and lipoprotein parameters (LDL cholesterol
      2.1%, -28.9%, and -35.5%; triglycerides -3.5%, -27.8%, and -33.0%; high-density
      lipoprotein cholesterol 3.3%, 13.1%, and 15. 7%; apolipoprotein B 3.8%, -23.1%,
      and -30.6%; and apolipoprotein A-I 4.0%, 8.2%, and 10.5% with placebo, and
      simvastatin 40 and 80 mg/day, respectively). The changes were consistent in
      patients with diabetes mellitus. One patient taking simvastatin 80 mg/day had an
      asymptomatic and reversible increase in hepatic transaminases 3 times above the
      upper limit of normal. Simvastatin 40 and 80 mg/day is effective in patients with
      mixed hyperlipidemia across the entire lipid and lipoprotein profile. The
      reductions in LDL cholesterol and triglycerides are large, significant, and dose
      dependent. The increase in high-density lipoprotein cholesterol was greater than
      that observed in patients with hypercholesterolemia, and appears dose dependent.

PMID- 10946034
TI  - Low-density lipoprotein particle size, triglycerides, and high-density
      lipoprotein cholesterol as risk factors for coronary heart disease in older
      Japanese-American men.
AB  - Decreased low-density lipoprotein (LDL) particle size is associated with coronary
      heart disease (CHD) risk among middle-aged Caucasian populations, and has been
      consistently correlated with increased plasma levels of triglyceride and
      decreased levels of high-density lipoprotein (HDL) cholesterol. This study
      examines whether these risk factors predict CHD among older Japanese-American
      men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as
      baseline, and 12-year follow-up for CHD events, a nested, case-control study was
      designed. One hundred forty-five incident CHD cases were identified and matched
      to 2 controls each. LDL particle diameter (size) was determined by gradient gel
      electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was
      associated with increased risk of incident CHD (relative risk 1.28, 95%
      confidence interval 1.01 to 1.63). After adjustment for baseline risk factors,
      the LDL size association was no longer statistically significant (relative risk
      1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis
      was used to define a composite variable for LDL size, triglycerides, and HDL
      cholesterol, this component predicted CHD independent of smoking, alcohol
      consumption, physical activity, body mass index, hypertension, diabetes, and beta
      blocker use (p <0.01). Therefore, this prospective analysis of data from older,
      Japanese-American men demonstrated that decreased LDL size is a univariate
      predictor of incident CHD, and that a composite risk factor of LDL size,
      triglyceride, and HDL cholesterol was a risk factor for CHD independent of other
      risk factors.

PMID- 10946035
TI  - Prognostic value of neurohormonal activation and cardiopulmonary exercise testing
      in patients with chronic heart failure.
AB  - We compared the value of plasma neurohormones and cardiopulmonary exercise
      testing for predicting long-term prognosis in patients with moderate congestive
      heart failure (CHF). We studied 264 consecutive patients with CHF due to left
      ventricular systolic dysfunction. Plasma atrial natriuretic peptide (ANP),
      norepinephrine, and endothelin-1 were measured at rest in all patients, who also
      underwent a symptom-limited maximal exercise with oxygen consumption (VO(2))
      determination. After a median follow-up of 789 days, 52 deaths and 31 heart
      transplantations occurred, of which 4 were urgent. In an univariate analysis, New
      York Heart Association functional class, systolic blood pressure at rest, left
      ventricular end-diastolic diameter, left ventricular ejection fraction, peak
      VO(2), percent of predicted peak VO(2), plasma ANP, plasma norepinephrine, and
      plasma endothelin-1 were associated with survival without urgent heart
      transplantation. In a multivariate stepwise regression analysis, only plasma ANP
      (p = 0.0001), left ventricular ejection fraction (p = 0.007), and plasma
      norepinephrine (p = 0.035), but neither peak VO(2) nor percentage of predicted
      peak VO(2), were independent predictors of death or urgent heart transplantation.
      Determination of plasma ANP and norepinephrine provides additional independent
      information for long-term prognostic determination compared with exercise testing
      alone. Measurement of plasma neurohormones should therefore be considered
      routinely as a complementary or alternative tool for identifying high-risk
      patients with moderate CHF.

PMID- 10946036
TI  - Neuroadrenergic activation and response to dobutamine in congestive heart failure
      secondary to idiopathic dilated cardiomyopathy.
AB  - Detection of contractile reserve is important in heart failure patients. To
      determine if detection of contractile reserve is influenced by neuroadrenergic
      activation, we examined the relation between dobutamine stress echocardiography
      (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with
      nonischemic left ventricular (LV) dysfunction (New York Heart Association class
      >III in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion
      score (WMS), and separately in WMS of hypokinetic segments and akinetic segments,
      were analyzed. A patient was considered to be responsive to dobutamine if the
      change in global WMS was >/=4. Twenty-three patients were responsive and 12 were
      not responsive to dobutamine. Plasma NE and baseline heart rate were
      significantly higher in nonresponsive patients (p <0.001). Changes in global WMS
      and in hypokinetic segment WMS were inversely related to either plasma NE (r 
      0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66,
      respectively). The change in akinetic segment WMS was related to plasma NE only
      (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV
      volume, baseline global WMS, or number of akinetic segments at baseline. Plasma
      NE >602 pg/ml predicted a blunted or absent contractile reserve at DSE
      (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence
      contractile reserve found at DSE in patients with heart failure due to
      nonischemic LV dysfunction.

PMID- 10946037
TI  - Validation of the ejection fraction-velocity ratio: a new simplified "function
      corrected" index for assessing aortic stenosis severity.
AB  - A new echocardiographic method for the evaluation of aortic stenosis (AS)
      severity has recently been introduced: the fractional shortening-velocity ratio
      (FSVR = fractional shortening/4 Vmax(2)). An important advantage of the method is
      the possibility of avoiding the difficulties related to the measurement of left
      ventricular outflow tract in calcific AS for assessing the continuity equation.
      FSVR, however, also shows some significant limitations especially in patients
      with regional wall motion abnormalities and conduction defects. To overcome this
      problem, we developed a new index: the ejection fraction-velocity ratio (EFVR =
      ejection fraction/4 Vmax(2)), where percent ejection fraction and Vmax have been
      obtained with an apical echocardiographic approach. In 343 consecutive patients
      with AS, aortic valve area was measured by cardiac catheterization (Gorlin),
      whereas FSVR and EFVR were calculated by echo-Doppler examination performed
      within 24 hours. Mean valve area was 0.70 +/- 0.30 cm(2), mean EFVR was 0.78 +/-
      0.41, and mean FSVR was 0.45 +/- 0.26. The linear correlation area-EFVR was
      highly significant (r = 0.88). Correlation valve area-FSVR was also significant
      (r = 0.82). EFVR allowed identification of patients with severe AS (area </=0.8
      cm(2)) with good sensitivity (88%) and specificity (85%), whereas FSVR
      demonstrated sensitivity of 88% and specificity of 73%. Thus, the EFVR, a very
      simple and not time-consuming index, is strongly related to aortic valve area in
      patients with AS. It allows identification of patients with severe AS with good
      sensitivity and specificity (better than FSVR). The EFVR, taking into
      consideration both ejection fraction and transvalvular pressure gradient, may be
      very useful in the evaluation of patients with AS and left ventricular
      dysfunction.

PMID- 10946038
TI  - Pulmonary vascular disease in Down's syndrome with complete atrioventricular
      septal defect.
AB  - We sought to determine the predisposing factors of pulmonary vascular disease
      (PVD) in complete atrioventricular septal defect. Down's syndrome is considered a
      risk factor for PVD, but the progression of PVD differs in each case.
      Morphometric analysis in autopsied hearts showed that Rastelli type A morphology
      had a narrower left ventricular outlet and a wider right ventricular outlet than
      did type C. In 81 consecutive patients with Down's syndrome who underwent cardiac
      catheterization, we estimated the following variables: Rastelli subtypes,
      pulmonary vascular resistance, pulmonary-to-systemic flow ratio, patients' age,
      and operative outcome. The hemodynamic variables in those <1 year old did not
      differ between the groups with type A and type C. However, all 5 patients with
      fatal pulmonary hypertension in early infancy had type A morphology. The lung
      histology revealed that 3 of these patients already had irreversible PVD. At >/=1
      year old, those with type A showed a significantly higher pulmonary vascular
      resistance (p <0.001) and a lower pulmonary to systemic flow ratio (p <0.05) than
      did those <1 year old. In contrast, neither of these variables in the type C
      group differed between those >/=1 and <1 year old. Moreover, those with type A
      had a greater risk of being contraindicated for surgical repair (p <0.05). We
      suspect, therefore, that type A morphology is an independent risk factor for PVD
      in those with Down's syndrome associated with this anomaly. This hemodynamic
      influence could become obvious once patients are >/=1 year old. It may also
      sometimes result in irreversible PVD even in early infancy.

PMID- 10946039
TI  - Moderators of the effect of social support on depressive symptoms in cardiac
      patients.
AB  - Social support and depression have been shown to affect the prognosis of coronary
      patients, and social support has been found to influence depression in community
      and patient samples. We investigated the characteristics of coronary patients
      whose depressive symptomatology was most likely to improve with social support.
      We predicted that social support would be most beneficial for the most severely
      depressed, the old, the poor, the most severely ill, and those with poor
      functional status. Patients (n = 590) with documented coronary artery disease
      were assessed for depressive symptoms, social support, and functional status
      while in hospital. They were reassessed for depression 1 month later during a
      home visit. Depression scores were lower at follow-up (p = 0.001), and
      improvement was more marked among those reporting more support (p <0.001). The
      social support effect was strongest among those with high levels of depression at
      baseline (p <0.001) and those with lower income (p = 0.01). Unexpectedly, social
      support was more strongly associated with improvement in younger patients (p =
      0.01). Social support did not interact with gender, disease severity, or
      functional status. These findings are partially consistent with the notion that
      social support is most effective for those who are most vulnerable and/or have
      few coping resources. These findings also have implications for the design and
      interpretation of psychosocial interventions.

PMID- 10946040
TI  - Nadolol inhibits reactive oxygen species generation by leukocytes and linoleic
      acid oxidation.
AB  - We studied the effect of short-term nadolol administration on the reactive oxygen
      species (ROS) generation by polymorphonuclear leukocytes and mononuclear cells in
      8 normal subjects. At a oral dose of 40 mg/day for 5 days, nadolol produced a
      decrease in the ROS generation by leukocytes. ROS generation by polymorphonuclear
      leukocytes decreased by 38% from 134 +/- 44 mV at baseline to 83 +/- 34 mV after
      5 days (p = 0.005), and ROS generation by mononuclear cells decreased by 33% from
      174 +/- 69 mV at baseline to 117 +/- 55 mV after 5 days (p = 0.015). There was
      also a significant reduction in linoleic acid oxidation as reflected by the lower
      levels of 9- and 13- hydroxy-octadecadienoic acid after 5 days. There was no
      change in the plasma thiobarbituric acid-reacting substances, a less sensitive
      index of oxidative damage to lipids. There was also no significant change in the
      levels of metatyrosine and orthotyrosine, which are known indexes of oxidative
      damage to amino acids and proteins. The absence of a significant change in
      metatyrosine, orthotyrosine, and thiobarbituric acid-reacting substances may
      reflect the short duration of nadolol administration and the decreased ROS load.
      Because ROS may induce lipid peroxidation, this inhibitory effect of nadolol on
      ROS generation by leukocytes and linoleic acid oxidation may inhibit low-density
      lipoprotein oxidation and thus atherogenesis. This effect may partly explain the
      favorable outcomes observed in patients with coronary artery disease on long-term
      beta-blocker therapy.

PMID- 10946041
TI  - Usefulness of the blood lymphocyte count in predicting recurrent instability and
      death in patients with unstable angina pectoris.

PMID- 10946042
TI  - Stent implantation neutralizes the impact of preintervention arterial remodeling
      on subsequent target lesion revascularization.

PMID- 10946043
TI  - Usefulness of providing physicians the results of risk factor assessments and
      treatment recommendations at discharge after coronary artery bypass grafting.

PMID- 10946044
TI  - Usefulness of the electrocardiogram in predicting stent patency in patients
      presenting with chest pain within one month of coronary stenting.

PMID- 10946046
TI  - Limited clinical value of exercise stress test for the screening of coronary
      artery disease in young, asymptomatic adult men.

PMID- 10946045
TI  - Relation of preservation of nitric oxide-dependent coronary vasomotor function to
      plasma vitamin C concentrations in cardiac transplant recipients.

PMID- 10946047
TI  - Aspirin use among women physicians in the United States.

PMID- 10946048
TI  - Relation of coronary artery calcium to exercise testing in healthy subjects.

PMID- 10946049
TI  - Prolongation of QT interval corrected for heart rate by Bazett's equation and
      linear formula as predictor of arrhythmic events after myocardial infarction.

PMID- 10946050
TI  - Effects of intravenous etilefrine in neurocardiogenic syncope induced by head-up
      tilt testing.

PMID- 10946051
TI  - Increased cardiac levels of nitric oxide in patients with chronic heart failure.

PMID- 10946052
TI  - Effect of estrogen on exercise electrocardiograms in healthy postmenopausal
      women.

PMID- 10946053
TI  - Myocardial contrast echocardiography with power Doppler imaging.

PMID- 10946054
TI  - Estrogen and atherothrombosis.

PMID- 10946055
TI  - Submissions, editorial process and impact factor 1992-2000: focus on Europe.

PMID- 10946056
TI  - Quantification of electrical remodeling in human atrial fibrillation.

PMID- 10946057
TI  - Familial hypertrophic cardiomyopathy: cornering the rat.

PMID- 10946058
TI  - Cardiac neural crest: the holy grail of cardiac abnormalities?

PMID- 10946059
TI  - Constriction of native coronary collaterals.

PMID- 10946060
TI  - Mitral valve prolapse in the dog: a model of mitral valve prolapse in man.

PMID- 10946061
TI  - Changes in atrial electrical properties following cardioversion of chronic atrial
      fibrillation: relation with recurrence.
AB  - OBJECTIVE: To study the reversibility of atrial electrical remodeling and its
      relation with recurrence in post-conversion chronic atrial fibrillation (CAF)
      patients. METHODS: In 28 drug-free CAF patients (mean AF duration 41+/-39 months)
      electrically converted to sinus rhythm effective refractory period (ERP) at 500
      ms, monophasic action potential at 90% of repolarization (MAPd90) at five cycle
      lengths (CL, 350, 400, 450, 500, 600 ms), and P wave duration were measured three
      times: within the interval 5-20 min post-conversion, 24 h and 1 month later.
      Fifteen subjects with no history of AF and normal atrial structure served as a
      control group. Patients were followed up for recurrence for 1 month; 12 relapsed.
      RESULTS: ERP changed from 205+/-20 to 243+/-31 to 241+/-24 ms (P<0. 001),
      attaining a level comparable to that of the controls (238+/-21 ms) within 24 h.
      MAPd90 significantly (P<0.001) increased (from 175+/-11 to 190+/-19 to 191+/-10
      ms at CL 350 ms and 201+/-12 to 234+/-20 and 233+/-23 ms at CL 600 ms) also
      reaching control levels within 24 h. MAPd90 exhibited an abnormal adaptation to
      rate only in the first evaluation. P wave duration was prolonged (137+/-33 ms)
      and exhibited a slower course of shortening (130+/-32 to 123+/-27 ms, P<0.001),
      reaching control levels within 1 month. Patients with higher values of MAPd90 at
      CL 350 in the immediate post-conversion period were more likely to relapse
      (P<0.005). CONCLUSIONS: ERP and repolarization shortening as a result of CAF are
      reversed within 24 h after conversion, while P wave duration reduces more slowly.
      Post-conversion MAPd90 values contain prognostic information for recurrence.

PMID- 10946063
TI  - Dynamic intracoronary thrombosis does not cause significant downstream platelet
      embolization.
AB  - OBJECTIVE: A mural intracoronary thrombus is a potential source of platelet
      emboli that may obstruct downstream microvessels, but this phenomenon has not
      been characterized. The present study aimed to assess the magnitude of myocardial
      platelet accumulation downstream of a mural intracoronary thrombus and its
      modification by a concomitant transient coronary occlusion (OC) or by treatment
      with aspirin. METHODS: The myocardial content of 99mTc-labelled platelets was
      analyzed in 26 pigs submitted to intimal injury of the left anterior descending
      coronary artery (LAD) followed by no intervention (n=6), 25-min OC (n=6), or 48
      min OC preceded (n=8) or not (n=6) by intravenous administration of 250 mg
      aspirin. RESULTS: After 2 h, 24 animals had had 12+/-1 cyclic flow reductions
      (CFRs) reflecting dynamic LAD thrombosis. Myocardial platelet content in the
      inferior region was similar among groups. Platelet content in the LAD region was
      not significantly different to that in the inferior region (129+/-19%, P=NS) in
      the no intervention group, but was increased following OC (172+/-20 and 312+/-71%
      after 25- and 48-min OC, respectively, P<0.05). Pre-treatment with aspirin
      lessened the number of CFRs but did not reduce platelet accumulation in LAD
      myocardium (483+/-148%). Myocardial platelet accumulation was not associated with
      the magnitude of platelet deposition in the LAD nor with the number of CFRs, but
      was correlated with myeloperoxidase activity (r=0.91, P<0.001) and with infarct
      size (r=0.52, P=0.05). Histological analysis frequently showed sparse platelets
      or small platelet or leukoplatelet aggregates in small vessels, but arteriolar
      emboli were rare. In none of seven additional experiments coronary angiography
      showed obstructions of arterial branches during CFRs. CONCLUSION: The magnitude
      of platelet embolization from a mural intracoronary thrombus into downstream
      myocardium is small despite the presence of repetitive CFRs.

PMID- 10946062
TI  - Transgenic rat hearts expressing a human cardiac troponin T deletion reveal
      diastolic dysfunction and ventricular arrhythmias.
AB  - OBJECTIVE: Familial hypertrophic cardiomyopathy (FHC) due to mutations of cardiac
      troponin T (cTnT) is associated with a high frequency of sudden death even in the
      absence of cardiac hypertrophy. To investigate the causal relationship of cTnT
      mutations and this particular phenotype, we sought to establish a transgenic rat
      model for the disease. METHODS: Transgenic rats were generated expressing human
      wild-type cTnT or two truncated cTnT molecules (del ex16, del ex15/16), resulting
      from an intron 15 splice donor site mutation previously observed in FHC patients.
      Transgenic rat hearts were characterized by histology, immunohistochemistry and
      in the 'working heart'. RESULTS: Human wild-type and del ex16 cTnT were stably
      expressed and incorporated into the sarcomere of transgenic cardiomyocytes. Del
      ex16 transgenic rats revealed a lower level of expression (4-5%) than human wt
      cTnT animals (25-40%). In the 'working heart' model del ex16 hearts exhibited
      significant systolic and diastolic dysfunction without cardiac hypertrophy. In
      contrast, human wt cTnT hearts showed improved contractile performance and
      moderate myocardial hypertrophy. After 6 months of daily physical exercise one
      del ex16 rat died suddenly and three out of five del ex16 hearts revealed
      ventricular tachycardia/fibrillation. No arrhythmia was observed in human wt cTnT
      expressors. Myofibrillar disarray was present in del ex16 hearts after training
      but not in human wild-type cTnT rats or non-transgenic controls. CONCLUSION: A
      human cTnT deletion overexpressed in transgenic rats exerts a dominant-negative
      effect and mimics the phenotype of FHC with diastolic dysfunction and
      arrhythmias. By contrast, human cTnT wild-type animals reveal a gain of function
      and cardiac hypertrophy without arrhythmias.

PMID- 10946065
TI  - Structural basis of regional dysfunction in acutely ischemic myocardium.
AB  - OBJECTIVE: Impaired systolic function in the normally perfused myocardium
      adjacent to an ischemic region - the functional border zone - is thought to
      result from mechanical interactions across the perfusion boundary. We
      investigated how segment orientation and vessel involved affect regional strains
      in the functional border zone and whether altered stresses associated with a step
      transition in contractility can explain the functional border zone. METHODS AND
      RESULTS: Regional epicardial strain distributions were obtained from measured
      displacements of radiopaque markers in open-chest anesthetized canines, and
      related to local myofiber angles and blood flows. The functional border zone for
      fiber strain was significantly narrower than that for cross-fiber strain and
      significantly wider for left anterior descending (LAD) than left circumflex (LCx)
      coronary occlusion (1.23 vs. 0.45 cm). A detailed three-dimensional computational
      model with a one-to-one relation between perfusion and myofilament activation and
      no transitional zone of intermediate contractility showed close agreement with
      these observations and significantly elevated stresses in the border zone.
      Differences between LAD and LCx occlusions in the model were due to differences
      in left ventricular systolic pressure and not to differences in perfusion
      boundary or muscle fiber orientation. The border zone was narrower for fiber
      strain than cross-fiber strain because systolic stiffness is greatest along the
      muscle fiber direction. CONCLUSION: Abnormal regional mechanics in the acute
      ischemic border arise from increased wall stresses without a transitional zone of
      intermediate contractility. Perfusion is more tightly coupled to fiber than cross
      fiber strain, and a wider functional border zone of fiber strain during LAD than
      LCx occlusion is primarily due to higher regional wall stresses rather than
      anatomic variations.

PMID- 10946066
TI  - Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated
      vascular and myocardial injury during 24 h of reperfusion.
AB  - OBJECTIVE: The purpose of this study was to compare protective effects of AMP579
      and adenosine (Ado) at reperfusion (R) on inhibition of polymorphonuclear
      neutrophil (PMN) activation, PMN-mediated injury to coronary artery endothelium,
      and final infarct size. METHODS: In anesthetized dogs, 1 h of left anterior
      descending coronary artery occlusion was followed by 24 h R and drugs were
      administered at R. Control (n=8, saline control), AMPI (n=7, AMP579, 50 microg/kg
      i.v. bolus followed by 3 microg/kg/min for 2 h), AMPII (n=7, AMP579, 50 microg/kg
      i.v. bolus), AMPIII (n=7, AMP579, 3 microg/kg/min i.v. for 2 h), and Ado (n=7,
      adenosine, 140 microg/kg/min i.v. for 2 h). RESULTS: AMP579 in vitro directly
      inhibited superoxide radical (O(-)(2)) generation (nM/5x10(6) PMNs) from PMNs
      dose-dependently (from 17+/-1* at 10 nM to 2+/-0.2* at 10 microM vs. activated
      30+/-2). However, inhibition of O(-)(2) generation by Ado at each concentration
      was significantly less than for AMP579. The IC(50) value for AMP579 (0.09+/-0.02
      microM) on O(-)(2) generation was significantly less than that of Ado (3.9+/-1. 1
      microM). Adherence of unstimulated PMN to postischemic coronary artery
      endothelium (PMNs/mm(2)) was attenuated in AMPI and AMPIII vs. Control (60+/-3*
      and 58+/-3* vs. Control 110+/-4), while Ado partially attenuated PMN adherence
      (98+/-3*). Accordingly, endothelial-dependent vascular relaxation was
      significantly greater in AMPI and AMPIII vs. Ado. At 24 h R, myocardial blood
      flow (MBF, ml/min/g) in the area at risk (AAR), confirmed by colored
      microspheres, in AMPI and AMPIII was significantly improved (0.8+/-0. 1* and
      0.7+/-0.1* vs. Control 0.3+/-0.04). Infarct size (IS, TTC staining) in AMPI and
      AMPIII was significantly reduced from 38+/-3% in Control to 21+/-4%* and 22+/
      3%*, respectively, confirmed by lower plasma creatine kinase activity (I.U./g
      protein) in these two groups (27+/-6* and 32+/-2* vs. 49+/-3). Cardiac
      myeloperoxidase activity (MPO, Abs/min) in the AAR was significantly reduced in
      AMPI and AMPIII vs. Control (36+/-11* and 35+/-10* vs. 89+/-10). However, changes
      in MBF, IS and MPO were not significantly altered by Ado. CONCLUSIONS: These data
      suggest that continuous infusion of AMP579 at R is more potent than adenosine in
      attenuating R injury, and AMP579-induced cardioprotection involves inhibition of
      PMN-induced vascular and myocardial tissue injury. *P<0.05 vs. Control.

PMID- 10946064
TI  - Roles of renin-angiotensin and endothelin systems in development of diastolic
      heart failure in hypertensive hearts.
AB  - OBJECTIVE: Although interest in diastolic heart failure is growing because of its
      clinical frequency, little is known about this type of heart failure. Our
      laboratory recently developed a diastolic heart failure model using Dahl salt
      sensitive rat. In this model, gene expression of angiotensin-converting enzyme
      and endothelin (ET) system in the left ventricle was enhanced at heart failure
      stage without downregulation of angiotensin type 1a receptor mRNA level. However,
      the roles of these humoral systems in the transition to diastolic failure remain
      unclear. METHODS: Subdepressor doses of angiotensin II type 1 (AT1) receptor and
      ET type A (ETA) receptor antagonists were administered in this model just after
      onset of hypertension, and their effects were investigated. RESULTS: Neither AT1
      nor ETA receptor blockade inhibited the early (13 weeks) compensatory left
      ventricular (LV) hypertrophy. This form of compensatory hypertrophy is associated
      with subnormal LV end-systolic stress, which was normalized by AT1 receptor
      blockade but not by ETA receptor blockade. Progression of LV hypertrophy and
      fibrosis and transition to heart failure (19 weeks) in the untreated rats were
      prevented by both antagonists, resulting in normalization of LV end-diastolic
      pressure and lung weight. AT1 receptor blockade, but not ETA receptor blockade,
      normalized time constant of LV relaxation. Enhanced gene expression for ET system
      in the left ventricle observed in the untreated rats was suppressed with AT1
      receptor antagonist administration. ETA receptor blockade slightly but
      significantly elevated the AT1a receptor mRNA level as compared with the
      untreated rats. CONCLUSIONS: RAS and ET system contribute to the transition to
      diastolic heart failure through the development of excessive hypertrophy and
      ventricular fibrosis in hypertensive heart diseases, however, neither RAS nor ET
      system is mandatory for normal compensation for pressure overload. RAS apparently
      causes such diastolic effects at least partly through the ET system.

PMID- 10946067
TI  - Increased glycoxidation and lipoperoxidation in the collagen of the myocardium in
      hemodialysis patients.
AB  - OBJECTIVE: The purpose of this study was to examine the glycoxidation and
      lipoperoxidation products in the collagen of the myocardium in hemodialysis (HD)
      patients and age-matched control subjects. METHODS: Cardiac samples from 15
      autopsied subjects (HD, n=6; control, n=9) were sequentially extracted with 0.9%
      NaCl and collagenase to obtain two fractions [soluble fraction (SF) and
      collagenase soluble fraction (CSF)]. The glycoxidation and lipoperoxidation
      products of these two fractions were measured by pentosidine-linked fluorescence
      (lambda(ex), 335; lambda(em), 385) and malondialdehyde (MDA)-linked fluorescence
      (lambda(ex), 390; lambda(em), 460), respectively. RESULTS: Both pentosidine- and
      MDA-linked fluorescence were found to have significantly increased more in the
      collagenase soluble fraction (CSF) extracted form the anterior and posterior wall
      in HD patients than in the controls (P<0. 05, control, n=9 vs. HD, n=6).
      Interestingly, the level of the lipid peroxides strongly correlated with that of
      the glycoxidation product in CSF (both P<0.0001 for the anterior and posterior
      wall). In contrast, in SF, which did not contain matrix collagen, neither
      significant difference nor correlation in the levels of pentosidine- and MDA
      linked fluorescence was observed in these two groups. CONCLUSION: the present
      study provides the first biochemical evidence for an increase in glycoxidation
      and a close link between glycoxidation and lipoperoxidation in the collagen of
      the myocardium in hemodialysis patients. These findings suggest that these two
      spontaneous chemical reactions in the collagen matrix of myocardium may
      synergistically contribute to cardiac damage in hemodialysis patients.

PMID- 10946068
TI  - Decreased neural crest stem cell expansion is responsible for the conotruncal
      heart defects within the splotch (Sp(2H))/Pax3 mouse mutant.
AB  - OBJECTIVE: Several mouse models of cardiac neural crest cell (NCC)-associated
      conotruncal heart defects exist, but the specific cellular and molecular defects
      within cardiac NCC morphogenesis remain largely unknown. Our objective was to
      investigate the underlying mechanisms resulting in outflow tract defects and why
      insufficient cardiac NCC reach the heart of the Splotch (Sp(2H)) mouse mutant
      embryo. METHODS: For this study we used in vitro cell culture techniques, in vivo
      mouse-chick chimeras, BrdU cell proliferation labeling, TUNEL labeling to
      visualize apoptosis and the molecular markers AP-2, Wnt-1 and Wnt-3a to
      characterize NCC morphogenesis in vivo. RESULTS: Expression of the NCC marker AP
      2 revealed an extensive reduction in migratory NCC, however the rates of cell
      proliferation and apoptosis were unaffected, and do not account for the Sp(2H)
      NCC-associated heart defects. Further expression analysis revealed that Wnt-1,
      but not Wnt-3a, is expressed at decreased levels within Sp(2H) and that the
      cardiac NCC fail to undergo normal NC stem cell proliferative expansion prior to
      migration while still in the neural folds. However, when placed into a wild-type
      matrix or a tissue culture environment, the Sp(2H) cardiac NCC could migrate
      normally. Additionally, this reduced population of Sp(2H) NC stem cells do
      migrate properly within the Sp(2H) environment, as observed by neurofilament
      expression and cardiac innervation. CONCLUSIONS: Taken together, all these data
      indicate that the Sp(2H) defect is intrinsic to the NC stem cells themselves and
      that there is a decrease in the number of pre-migratory cardiac NCC that form. It
      appears that this decrease in NCC number is the primary defect that ultimately
      leads to a lack of a cardiac NCC-derived Sp(2H) outflow tract septum.

PMID- 10946069
TI  - HMG CoA reductase inhibition reduces sarcolemmal Na(+)-K(+) pump density.
AB  - OBJECTIVES: HMG CoA reductase inhibitors reduce cellular availability of
      mevalonate, a precursor in cholesterol synthesis. Since the cholesterol content
      of cell membranes is an important determinant of Na(+)-K(+) pump function we
      speculated that treatment with HMG CoA reductase inhibitors affects Na(+)-K(+)
      pump activity. METHODS: We treated rabbits and rats for 2 weeks with the HMG CoA
      reductase inhibitor lovastatin and measured Na(+)-K(+) pump current (I(p)) in
      isolated rabbit cardiac myocytes using the whole cell patch-clamp technique, K
      dependent p-nitrophenyl phosphatase (p-NPPase) activity in crude myocardial and
      skeletal muscle homogenates, and vanadate-facilitated 3H-ouabain binding in
      intact skeletal muscle samples from rats. RESULTS: Treatment with lovastatin
      caused statistically significant reductions in I(p), myocardial and skeletal
      muscle K-dependent p-NPPase activity and 3H-ouabain binding in the myocardium and
      skeletal muscle. The lovastatin-induced decrease in I(p) was eliminated by
      parenteral co-administration of mevalonate. However, this was not related to
      cardiac cholesterol content. CONCLUSIONS: Treatment with lovastatin reduces Na(+)
      K(+) pump activity and abundance in rabbit and rat sarcolemma.

PMID- 10946070
TI  - Facilitation of L-type calcium currents by diastolic depolarization in cardiac
      cells: impairment in heart failure.
AB  - OBJECTIVE: Decay kinetics of the voltage-gated L-type Ca(2+) current (I(CaL))
      control the magnitude of Ca(2+) influx during the cardiac action potential. We
      investigated the influence of changes in diastolic membrane potential on I(CaL)
      decay kinetics in cardiac cells. METHODS: Cells were isolated enzymatically from
      rat ventricles, human right atrial appendages obtained during corrective heart
      surgery and left ventricles from end-stage failing hearts of transplant
      recipients. The whole-cell patch-clamp technique was used to evoke I(CaL) by a
      100-ms depolarizing test pulse to -10 mV. Conditioning potentials between -80 and
      0 mV were applied for 5 s prior to the test pulse. RESULTS: Depolarizing the
      cells between -80 and -50 mV prior to the test pulse slowed the early
      inactivation of I(CaL) both in rat ventricular and human atrial cells. This
      slowing resulted in a significant increase of Ca(2+) influx. This type of
      facilitation was not observed when the sarcoplasmic reticulum (SR) Ca(2+) content
      was depleted using ryanodine which reduced the rate of inactivation of I(CaL), or
      when Ba(2+) replaced Ca(2+) as the permeating ion. Facilitation was favored by
      intracellular cAMP-promoting agents that, in addition to increasing current peak
      amplitude, enhanced the fast Ca(2+)-dependent inactivation of I(CaL).
      Facilitation was impaired in atrial and ventricular human failing hearts.
      CONCLUSION: Decay kinetics of I(CaL) are regulated by the diastolic membrane
      potential in rat and human cardiomyocytes. This regulation, which associates
      slowing of I(CaL) inactivation with reduced SR Ca(2+) release and underlies
      facilitation of Ca(2+) channels activity, may have profound physiological
      relevance for catecholamines enhancement of Ca(2+) influx. It is impaired in
      failing hearts, possibly due to lowered SR Ca(2+) release.

PMID- 10946071
TI  - Experimental heart failure in rats: effects on cardiovascular circadian rhythms
      and on myocardial beta-adrenergic signaling.
AB  - OBJECTIVES: Patients with chronic heart failure frequently show blunted circadian
      blood pressure profiles. The mechanisms involved in the loss of physiological day
      night variation are still unclear, but a continuously active sympathetic nervous
      system could play a role. The present study evaluated long-term consequences of
      rat heart failure on cardiovascular circadian patterns in vivo, and on density
      and function of cardiac beta-adrenoceptor subtypes in vitro, as a marker of
      cardiac adrenergic drive. METHODS: Heart failure in rats was induced by coronary
      artery ligation leading to infarct sizes of >30% of left ventricular
      circumference. Blood pressure and heart rate were monitored for 10 weeks after
      infarction using radiotelemetry. Density and function of cardiac beta(1) and
      beta(2)-adrenoceptors were measured by radioligand binding and adenylyl cyclase
      stimulation. RESULTS: During the activity period at night blood pressure and
      heart rate were lower in rats with heart failure than in sham controls, leading
      to reduced night-day variation in the heart failure group. Depression of
      circadian rhythmicity in blood pressure was found over the whole study period,
      while that in heart rate occurred with a lag-time of several weeks. In failing
      left ventricles beta-adrenoceptors showed reduced high affinity agonist binding,
      a shift in the beta(1):beta(2) ratio towards the beta(2)-subtype, and decreased
      beta(1)-adrenergic stimulation of adenylyl cyclase. In right ventricles no
      differences were found between failing and control rats. The blunted nocturnal
      increase in blood pressure and heart rate as well as beta(1)-adrenergic
      desensitization were correlated with the severity of left ventricular
      dysfunction. CONCLUSIONS: Heart failure in rats leads to disturbed circadian
      patterns in blood pressure and heart rate, and to desensitization of cardiac
      beta(1)-adrenoceptors, indicating chronic sympathetic overactivity.

PMID- 10946072
TI  - Measurement of coronary collateral flow and resistance in the presence of an open
      critical stenosis, and the response to intra-arterial thrombosis.
AB  - OBJECTIVE: (1) Can one measure coronary collateral flow around an open critical
      stenosis? (2) Does intracoronary platelet thrombosis affect native coronary
      collateral vessels? METHODS: We measured regional myocardial blood flow by the
      radioactive microsphere technique in seven anaesthetised dogs with an ultrasonic
      flowmeter on the circumflex branch of the left coronary artery (LCx).
      Measurements were made (a) in a control period, (b) after induction of a tight
      stenosis on the LCx, and (c) after additional arterial damage at the stenosis to
      induce intraluminal thrombosis. Collateral flow was calculated from LCx tissue
      flow(in ml/min/g tissue) minus LCx flowmeter flow which is in ml/min. Therefore,
      it was necessary to use scaling by reference back to the control measurements and
      conversion to ml/min/g tissue equivalent. RESULTS: LCx stenosis induced
      collateral flow from the other coronary arteries into the LCx area of supply,
      which decreased (mean+/-S.E.) from 0.23+/-0.03 to 0.15+/-0.05 ml/min/g tissue
      with thrombosis. Collateral resistance correspondingly increased with thrombosis
      from 187.6+/-18. 2 to 1069+/-544 mmHg/ml/min/g (P<0.02). CONCLUSION: Coronary
      collateral flow around an open stenosis can be measured by reference back to
      control conditions. The coronary collaterals vasoconstrict in the presence of
      thrombosis even though they are in the stream of blood coming from normal
      coronary arteries.

PMID- 10946073
TI  - Modulation of intrinsic cardiac neurons by spinal cord stimulation: implications
      for its therapeutic use in angina pectoris.
AB  - OBJECTIVE: Electrical stimulation of the dorsal aspect of the upper thoracic
      spinal cord is used increasingly to treat patients with severe angina pectoris
      refractory to conventional therapeutic strategies. Clinical studies show that
      spinal cord stimulation (SCS) is a safe adjunct therapy for cardiac patients,
      producing anti-anginal as well as anti-ischemic effects. However, little
      information is yet available about the underlying mechanisms involved. METHODS:
      In order to determine its mechanism of action, the effects of SCS on the final
      common integrator of cardiac function, the intrinsic cardiac nervous system, was
      studied during basal states as well as during transient (2 min) myocardial
      ischemia. Activity generated by intrinsic cardiac neurons was recorded in 9
      anesthetized dogs in the absence and presence of myocardial ischemia before,
      during and after stimulating the dorsal T1-T2 segments of the spinal cord at 66
      and 90% of motor threshold using epidural bipolar electrodes (50 Hz; 0.2 ms;
      parameters within the therapeutic range used in humans). RESULTS: The SCS
      suppressed activity generated by intrinsic cardiac neurons. No concomitant change
      in monitored cardiovascular indices was detected. Neuronal activity increased
      during transient ventricular ischemia (46%), as well as during the early
      reperfusion period (68% compared to control). Despite that, activity was
      suppressed during both states by SCS. CONCLUSIONS: SCS modifies the capacity of
      intrinsic cardiac neurons to generate activity. SCS also acts to suppress the
      excitatory effects that local myocardial ischemia exerts on such neurons. Since
      no significant changes in monitored cardiovascular indices were observed during
      SCS, it is concluded that modulation of the intrinsic cardiac nervous system
      might contribute to the therapeutic effects of SCS in patients with angina
      pectoris.

PMID- 10946074
TI  - Angiotensin II-induced contractions in human internal mammary artery: effects of
      cyclooxygenase and lipoxygenase inhibition.
AB  - OBJECTIVE: This study investigated, in isolated human internal mammary artery,
      the involvement of the cyclooxygenase and the lipoxygenase pathways of
      arachidonic acid metabolism in the contraction induced by angiotensin II.
      METHODS: Rings of human internal mammary arteries were suspended in organ baths
      for recording of isometric tension. In addition, the release of eicosanoids in
      response to angiotensin II (0.3 microM) was measured by enzyme immunoassay.
      RESULTS: In human arterial rings without endothelial dependent relaxation in
      response to substance P or acetylcholine, the angiotensin II-induced contractions
      were significantly (P<0.05) reduced by 27% in the presence of GR32191 0.3 microM
      (thromboxane A(2) (TXA(2)) receptor antagonist) but remained unchanged in the
      presence of dazoxiben 100 microM (thromboxane synthase inhibitor). In addition,
      angiotensin II failed to modify TXB(2) and 6-keto-PGF(1alpha) production. These
      results suggest the contribution of a TXA(2)/PGH(2) agonist other than TXA(2) in
      angiotensin II-induced contractions. However, indomethacin increased (P<0.05)
      angiotensin II-mediated contractile response and cysteinyl leukotriene
      production, suggesting a redirection of arachidonic acid metabolism from the
      cyclooxygenase pathway to the lipoxygenase pathway. Indeed, the contractions
      induced by angiotensin II were inhibited (P<0.05) by phenidone 100 microM
      (cyclooxygenase and lipoxygenase inhibitor), baicalein 100 microM (5-, 12- and 15
      lipoxygenases inhibitor), AA861 10 microM (5-lipoxygenase inhibitor) and MK571 1
      microM (CysLT(1) receptor antagonist). Cysteinyl leukotrienes were released in
      response to angiotensin II (pg/mg dry weight tissue: 32+/-9 (basal, n=6) vs. 49+/
      9 (angiotensin II 0.3 microM, n=6), P<0.05). LTD(4), and at a lesser degree
      LTC(4), induced contractions of internal mammary artery and MK571 1 microM
      abolished the contraction to LTD(4). CONCLUSIONS: This study suggests that the in
      vitro vasoconstrictor effects of angiotensin II in human internal mammary artery
      are enhanced at least in part by eicosanoids produced by the cyclooxygenase
      pathway, probably PGH(2), acting on TXA(2)/PGH(2) receptors, and by lipoxygenase
      derived products, particularly cysteinyl leukotrienes acting on CysLT(1)
      receptors.

PMID- 10946075
TI  - Evidence for modulation of genes involved in vascular adaptation by prolonged
      exposure of endothelial cells to shear stress.
AB  - OBJECTIVE: Shear stress is known to modulate gene expression. However, the
      molecular link between blood flow and long-time vessel adaptation is still
      unclear. In this study, the variations of gene expression by prolonged shear
      stress exposure was investigated in order to identify genes possibly involved in
      flow dependent vascular adaptation. METHODS: Human umbilical vein endothelial
      cells (HUVECs) were exposed to laminar shear stress (6 dyn/cm(2); 24 h) and
      analyzed by differential display (DDRT-PCR). Flow-modulation of differentially
      expressed genes by different exposure times (4, 24, 48 h) and in human cardiac
      microvascular endothelial cells (HCMECs) (24 h exposure) was analyzed by RT-PCR
      and northern blotting. RESULTS: DDRT-PCR analysis displayed 13 down- and 20 up
      regulated products in response to flow. Four known genes were identified:
      Angiopoietin-2, a protein reported to reduce vessel stability, was progressively
      (4-48 h) down-regulated by shear stress. The induction of the anti-angiogenic
      metalloproteinase METH-1 was maximal after 4 h exposure and sustained over the
      time (24-48 h). Growth arrest-specific mRNA 3 (gas3) and calpactin 1 light chain
      (p11) were up-regulated only by prolonged exposure (24-48 h). Analysis of the
      expression of angiopoietin-2, METH-1, gas3, and p11 in shear stress exposed (24
      h) HCMECs showed modulation patterns comparable to those observed in HUVECs.
      CONCLUSION: Since angiopoietin-2 and METH-1 are known to be involved in vessel
      regression/stabilization, the reported modulation of these genes by prolonged
      shear stress exposure strongly suggests their participation in flow-dependent
      vascular adaptation.

PMID- 10946076
TI  - Mechanism of Ca(2+) overload in endothelial cells exposed to simulated ischemia.
AB  - OBJECTIVE: Several studies have shown that myocardial ischemia leads to
      functional failure of endothelial cells (EC) whereby disturbance of Ca(2+)
      homeostasis may play an important role. The mechanisms leading to Ca(2+)
      disbalance in ischemic EC are not fully understood. The aim of this study was to
      test effects of different components of simulated ischemia (glucose deprivation,
      anoxia, low extracellular pH (pH(o)) and lactate) on Ca(2+) homeostasis in EC.
      METHODS: Cytosolic Ca(2+) (Ca(i)), cytosolic pH (pH(i)) and ATP content were
      measured in cultured rat coronary EC. RESULTS: In normoxic cells 60 min glucose
      deprivation at pH(o) 7.4 had no effect on pH(i). It only slightly increased Ca(i)
      and decreased ATP content. Reduction of pH(o) to 6.5 under these conditions led
      to marked cytosolic acidosis and Ca(i) overload, but had no effect on ATP
      content. Anoxia at pH(o) 6.5 had no additional effect on Ca(i) overload, but
      significantly reduced cellular ATP. Addition of 20 mmol/l lactate to anoxia at
      pH(o) 6.5 accelerated Ca(i) overload due to faster cytosolic acidification.
      Acidosis-induced Ca(i) overload was prevented by inhibition of Ca(2+) release
      channels of endoplasmic reticulum (ER) with 3 micromol/l ryanodine or by pre
      emptying the ER with thapsigargin. Re-normalisation of pH(o) for 30 min led to
      recovery of pH(i), but not of Ca(i). CONCLUSION: The ischemic factors leading to
      cytosolic acidosis (low pH(o) and lactate) cause Ca(i) overload in endothelial
      cells, while anoxia and glucose deprivation play only a minor role. The ER is the
      main source for this Ca(i) rise. Ca(i) overload is not readily reversible.

PMID- 10946077
TI  - Nitrovasodilators and heart rate: more than the arterial baroreflex.

PMID- 10946078
TI  - Periventricular leukomalacia: an important cause of visual and ocular motility
      dysfunction in children.
AB  - The immature visual system in infants born preterm is vulnerable to adverse
      events during the perinatal period. Periventricular leukomalacia affecting the
      optic radiation has now become the principal cause of visual impairment and
      dysfunction in children born prematurely. Visual dysfunction is characterized by
      delayed visual maturation, subnormal visual acuity, crowding, visual field
      defects, and visual perceptual-cognitive problems. Magnetic resonance imaging is
      the method of choice for diagnosing this brain lesion, which is associated with
      optic disk abnormalities, strabismus, nystagmus, and deficient visually guided
      eye movements. Children with periventricular leukomalacia may present to the
      ophthalmologist within a clinical spectrum from severe cerebral visual impairment
      in combination with cerebral palsy and mental retardation to only early-onset
      esotropia, normal intellectual level, and no cerebral palsy. Optimal educational
      and habilitational strategies need to be developed to meet the needs of this
      group of visually impaired children.

PMID- 10946080
TI  - Electrophysiology in the investigation of acquired retinal disorders.
AB  - Electrophysiological research on acquired retinal disorders, both common and
      rare, is reviewed. Age is a major factor influencing electroretinogram (ERG) and
      electro-oculogram (EOG) findings. Bipolar or Muller cell death in the aging
      retina could account for much of the amplitude decline that is observed with age.
      In diabetic retinopathy, the oscillatory potentials can monitor the progression
      of the disease and indicate neuronal alterations rather than diabetic angiopathy
      of the retina. Human ERG studies on glaucoma concentrated on ERG measures that
      are dominated by inner retinal contributions. It has been shown that the pattern
      ERG can serve as a predictor of ocular hypertension's progression to glaucoma. In
      retinal disorders caused by endogenous intoxication, such as hepatic retinopathy,
      or exogenous intoxication from chronic lead exposure, ERG changes give an
      objective measure of the damage and allow to study the pathophysiological
      mechanisms that are involved. Inflammations of the choroid and the retina affect
      the standard ERG when they are diffuse. In central serous chorioretinopathy,
      functional disturbances can be revealed not only in the photoreceptors but also
      in the middle and inner retinal layers with the use of focal stimuli. Choroidal
      melanoma leads to large reductions of the EOG light peak-to-dark trough ratio
      through its influence on the transepithelial potential of the retinal pigment
      epithelium (RPE). In cancer-associated retinopathy, both the rod and cone ERGs
      are reduced. However, selective cone dysfunction has been described. In melanoma
      associated retinopathy, the long flash ERG may reveal a specific
      pathophysiological mechanism, namely the affection of the ON-pathway with
      preservation of the OFF-pathway. ERG measurements can reveal vitamin A deficiency
      and are altered in cases with a mutation in the gene for the retinol binding
      protein in which other organs are not affected. Photochemical damage to the
      retina from light emission by the operating microscope can be assessed by
      electrophysiological methods.

PMID- 10946079
TI  - Fluorescence properties and metabolic features of indocyanine green (ICG) as
      related to angiography.
AB  - Indocyanine green (ICG) is a fluorescent dye that has been used for the imaging
      of retinal and choroidal vasculatures for more than 30 years. Its high molecular
      weight, specific metabolic features, and its infrared spectra make the
      specificity of the images obtained with this dye in ophthalmology. The focus of
      this paper is to review the basic properties of ICG and to show how some clinical
      features related to basic properties also depend on the instrumentation used to
      perform ICG angiography. Indocyanine green has a complex molecular structure that
      leads to amphiphilic properties, that is, both hydrophilic and lipophilic
      properties. These properties explain that a specific interaction with
      phospholipids influences the emission spectrum and the fluorescence yield of ICG.
      The composition of cell membranes mainly composed of phospholipid bilayers is
      consistent with a binding and/or a diffusion of ICG molecules observed on
      angiograms. Likewise, ICG can bind to the lipid component of miliary drusen,
      explaining their hyperfluorescence. A knowledge of ICG basic properties and
      interactions may allow a better understanding of angiograms performed with this
      dye.

PMID- 10946081
TI  - The role of the immune system in conjunctival wound healing after glaucoma
      surgery.
AB  - The immune system has a fundamental role in the development and regulation of
      ocular healing, which plays an important role in the pathogenesis of most
      blinding diseases. This review discusses the mechanisms of normal wound healing,
      describing the animal and fetal wound healing models used to provide further
      insight into normal wound repair. In particular, conjunctival wound repair after
      glaucoma filtration surgery will be used to illustrate the contributions that the
      different components of the immune system make to the healing process. The
      potential role of macrophages, the possible regulatory effect of lymphocytes, and
      the important role of growth factors and cytokines in the wound healing reaction
      are discussed. The significance of the immune system in the pathogenesis of
      aggressive conjunctival scarring is addressed, particularly assessing the
      predisposing factors, including drugs, age, and ethnicity. The rationale behind
      the pharmacological agents currently used to modulate the wound healing response
      and the effects these drugs have on the function of the immune system are
      described. Finally, potential new therapeutic approaches to regulating the wound
      healing response are reported.

PMID- 10946082
TI  - Unilateral lid retraction during pregnancy.
AB  - A 32-year-old woman noted left lid retraction during pregnancy. Examination
      revealed unilateral enophthalmos without symptoms of diplopia or sinus disease.
      Orbital imaging showed characteristic features of the silent sinus syndrome,
      which were confirmed intraoperatively. The clinical and imaging attributes of
      this syndrome are discussed, including possible mechanisms of disease
      development. Management strategies are summarized. A brief discussion of the
      differential diagnosis of enophthalmos is also included.

PMID- 10946083
TI  - Node way out.
AB  - A 47-year-old woman without a history of melanoma experienced visual
      hallucinations, abnormal visual field, and an ERG suggestive of melanoma
      associated retinopathy (MAR). A lymph node biopsy showed malignant melanoma.
      Appropriate evaluation, management, and treatment of MAR is discussed.

PMID- 10946084
TI  - Relevance of tissue factor and tissue factor pathway inhibitor for
      hypercoagulable state in the lungs of patients with idiopathic pulmonary
      fibrosis.
AB  - We investigated the role of tissue factor (TF) and tissue factor pathway
      inhibitor (TFPI) in the lungs of patients with idiopathic pulmonary fibrosis
      (IPF). Bronchoalveolar lavage (BAL) fluid was obtained from 22 patients with IPF,
      and the levels of TF and TFPI antigen were measured by ELISA. The TF and TFPI
      levels in BAL fluid supernatant were significantly higher in IPF patients than in
      normal controls. In addition, both levels were significantly higher in advanced
      cases than in nonadvanced cases. There was a significant correlation between the
      TF and TFPI levels. Localization of TF and TFPI antigens was investigated by
      immunohistochemical staining. Both antigens were mainly localized in hyperplastic
      cuboidal epithelial cells, suggesting that the widespread distribution of these
      cells contributed to the increase of TF and TFPI antigen levels in the lungs of
      IPF patients. To assess whether TF activity is counterbalanced by TFPI in the
      lungs of IPF patients, we examined procoagulant activity and TF activity. It was
      found, however, that both procoagulant and TF activities were significantly
      higher in the BAL fluid supernatant of IPF patients than in that of normal
      controls, which suggested that TFPI was actually increased, but the increase was
      insufficient to counterbalance TF, leading to the development of a
      hypercoagulable state in the lungs of IPF patients.

PMID- 10946085
TI  - Relationship between lipoprotein(a) phenotypes and plaminogen activator inhibitor
      type 1 in diabetic patients.
AB  - It has been demonstrated in vitro that lipoprotein(a) [Lp(a)] increases the
      endothelial synthesis of plasminogen activator inhibitor 1 (PAI-1). However, this
      effect in vivo is controversial, and the possible relationship between PAI-1 and
      Lp(a) phenotypes has not been evaluated. The aim of the study was to determine
      the influence of Lp(a) and its phenotypes on PAI-1 serum concentrations in
      diabetic patients. For this purpose we include 75 Caucasian diabetic patients (34
      consecutive type I and 41 consecutive type II) without late diabetic
      complications. Lp(a) and PAI-1 were assessed by ELISA. Lp(a) phenotypes were
      determined by SDS-PAGE followed by immunoblotting, and grouped according to size
      in small (F,B,S1,S2), big (S3,S4), and null. A linear correlation between Lp(a)
      and PAI-1 was not observed either as a whole or when type I and type II diabetic
      patients were analyzed separately. However, significant differences were detected
      in PAI-1 levels when Lp(a) phenotypes were considered (small: 42.1+/-31.8 ng/mL;
      big: 37.2+/-26.1 ng/mL; null: 14.4+/-14.4; p< 0.05). The significant differences
      were due to the low PAI-1 concentrations observed in patients with null
      phenotype. Our results suggest that fibrinolytic activity might be preserved in
      diabetic patients with null Lp(a) phenotype. Furthermore, it could be speculated
      that diabetic patients with null phenotype should be considered at low risk to
      develop cardiovascular disease.

PMID- 10946086
TI  - High prevalence of protein-dependent and protein-independent antiphospholipid and
      other autoantibodies in healthy elders.

PMID- 10946087
TI  - Potentiation of ganodermic acid S on prostaglandin E(1)-induced cyclic AMP
      elevation in human platelets.
AB  - Ganodermic acid S (GAS), isolated from the Chinese medicinal fungus Ganoderma
      lucidum (Fr.) Karst (Polyporaceae), exhibits inhibitory effects on platelet
      responses to various aggregating agonists. Our study demonstrated that GAS also
      participated in potentiating the response of human gel-filtered platelets to
      prostaglandin (PG) E(1). GAS at <20 microM did not show any significant change of
      basal cyclic AMP level in gel-filtered platelets. However, GAS potentiated the
      PGE(1)-evoked cyclic AMP level in a bell-shaped, concentration-dependent manner.
      The agent at 7.5 microM enhanced the level up to 1.8-fold of that evoked by
      PGE(1) alone. Collagen did not inhibit the PGE(1)-induced cyclic AMP level in
      platelets pretreated with GAS at 6 to 7.5 microM. In the presence of 7.5 microM
      GAS, the agent enhanced the inhibition of PGE(1) on platelet response to collagen
      in: phosphorylation of myosin light chain and pleckstrin; alpha-granule
      secretion; cell aggregation and protein-tyrosine phosphorylation. In addition,
      the agent along with PGE(1) almost abolished the dense-granule secretion and
      thromboxane (TX) B(2) formation. The results suggest that GAS played an
      additional role in potentiating the PGE(1)-induced cyclic AMP synthesis. GAS and
      PGE(1) inhibited additively the platelet response to collagen.

PMID- 10946088
TI  - Effect of thrombopoietin and granulocyte colony-stimulating factor on platelets
      and polymorphonuclear leukocytes.
AB  - Thrombopoietin (TPO) and granulocyte colony-stimulating factor (G-CSF) may be
      administered together in aplastic patients. We evaluated the effect of both
      cytokines alone or combined on platelets and polymorphonuclear leukocytes (PMN)
      functional responses. TPO, G-CSF, or the combination of both cytokines, induced
      neither platelet nor PMN activation. TPO but not G-CSF synergized with threshold
      ADP concentrations to induce maximal aggregation and ATP release. The synergistic
      effect of TPO with ADP was not modified by the presence of G-CSF. Flow cytometry
      studies have shown that thrombin-induced loss of GPIb from platelet surface was
      significantly increased by pretreatment of platelets with TPO, G-CSF, or both
      cytokines. P-selectin expression induced by thrombin was augmented by TPO, but
      not by G-CSF. Coincubation of the cells with TPO and G-CSF did not modify the
      values obtained with TPO alone. Expression of CD11b on PMN surface was augmented
      by G-CSF or fMLP. G-CSF-treated PMN increased the effect of fMLP on CD11b
      expression. TPO did not modify either basal levels of CD11b or the increased
      expression induced by G-CSF or fMLP. Incubation of PMN with both cytokines showed
      no differences compared to G-CSF alone. Platelet-PMN aggregates induced by
      thrombin in whole blood were augmented by TPO. G-CSF alone neither synergized
      with thrombin nor changed the results observed with TPO. These data show that in
      vitro functional responses of platelets, or PMN induced by TPO or G-CSF alone,
      were neither further increased nor inhibited by treatment of the cells with both
      cytokines.

PMID- 10946089
TI  - Transcellular formation of thromboxane A(2) in mixed incubations of endothelial
      cells and aspirin-treated platelets strongly depends on the prostaglandin I
      synthase activity.
AB  - Despite an almost total suppression of platelet cyclooxygenase (COX) by aspirin,
      as monitored ex vivo, incomplete suppression of thromboxane (Tx)A(2) metabolite
      excretion has been detected in some patients with unstable angina treated with
      low doses of aspirin. A plausible explanation for this finding is the
      transcellular formation of TxA(2) by platelets from prostaglandin H(2) released
      by endothelial cells. We recently reported that probably only COX and PGI
      synthase (PGIS) are involved in the biosynthesis of prostanoids in endothelial
      cells. The present work was thus focused to ascertain the dependence of the
      transcellular biosynthesis of TxA(2), by endothelial cells and aspirin-treated
      platelets, on the relative activity of these enzymes. Synthesis of eicosanoids
      from exogenous and endogenous arachidonic acid (AA) by mixed incubations of human
      umbilical vein endothelial cells (HUVEC) in culture and aspirin-treated platelets
      were determined by HPLC and enzyme immune assay. The ratio of COX to PGIS
      activities was modified in HUVEC by treatment with interleukin-1beta (IL-1beta).
      Transcellular formation of TxA(2) was only relevant when HUVEC overexpressed COX
      2 (monitored by RT-PCR and Western blotting), and in these conditions TxA(2)
      formation started 2 minutes after substrate addition. Progression curves showed
      that half-times (t(1/2)) of the COX and PGIS activity were 2.73 and 0.47 minutes,
      respectively, in resting HUVEC, whereas these values for IL-1beta-treated cells
      were 1.33 and 0.07 minutes, respectively, indicating that expression of COX-2
      increased the rate of PGIS "suicide" inactivation. Collectively, these results
      indicated that not only enhanced COX activity but also substantial PGIS
      inactivation was required for significant transcellular biosynthesis of TxA(2).

PMID- 10946090
TI  - Responses to aggregating agents after cleavage of GPIb of human platelets by the
      O-sialoglycoprotein endoprotease from Pasteurella haemolytica- potential
      surrogates for Bernard-Soulier platelets?
AB  - Most proteolytic enzymes that cleave glycoprotein lb (GPlb) also cleave other
      glycoproteins or receptors on the surface of platelets. We have used an O
      sialoglycoprotein endoprotease from Pasteurella haemolytica that selectively
      cleaves the heavily O-glycosylated GPlb, but does not cleave N-linked
      glycoproteins or unglycosylated proteins. Isolated, [14C]serotonin-labeled
      platelets in Tyrode-albumin solution were incubated with 10 microg/mL
      endoprotease for 60 minutes at 37 degrees C. These platelets did not release
      [14C]serotonin, had no detectable GPIb, and were unresponsive to ristocetin/von
      Willebrand factor. Compared with control platelets, aggregation and release of
      [14C]serotonin by the endoprotease-pretreated platelets were inhibited in
      response to low concentrations of thrombin, SFLLRN (the PAR-1-activating
      peptide), collagen, and U46619 (a thromboxane A(2) mimetic); aggregates were
      smaller in size. The presence of fibrinogen overcame the inhibition of responses
      induced by SFLLRN, collagen, and U46619. With fibrinogen, primary ADP-induced
      aggregation was scarcely affected by pretreatment with the endoprotease. Thus,
      the PAR-1 receptor for thrombin, and receptors for collagen, thromboxane A(2),
      fibrinogen (GPIIb/IIIa), and ADP appear to function normally on the endoprotease
      pretreated platelets. Since only GPIb is cleaved by the endoprotease, these
      platelets seem to provide potential surrogates for Bernard-Soulier syndrome
      platelets for further studies of platelet functions in this condition.

PMID- 10946091
TI  - Long-term effect of 17beta-estradiol and thrombin on tissue factor pathway
      inhibitor release from HUVEC.
AB  - In spite of the increasing evidence that estrogens have protective effects on the
      vascular system, the evidence that estrogens may contribute to the risk of
      thrombosis is still being debated. We investigated the effect of 17beta-estradiol
      (E2) on tissue factor pathway inhibitor (TFPI) release from of cultured human
      umbilical vein endothelial cells (HUVEC). In this study HUVEC were harvested by
      collegenase treatment and cultured in multiwelled plates with medium 199
      supplemented with 10% fetal calf serum and antibiotics. The cells were incubated
      in the presence or absence of E2 (1 and 100 nM) with/without thrombin (4 U/mL)
      for 6 or 24 hours. After the incubations TFPI level of media were measured by
      IMUBIND Total Eliza kit. Our results demonstrates that E2 at physiological
      concentrations decreases the release of TFPI from HUVEC significantly. Thrombin
      also decreases TFPI antigen levels detected in culture media. When combined with
      thrombin the effect of estrogen is not visible due the much higher effectivity of
      thrombin in diminishing TFPI levels. These results show that E2 shifts the
      hemostatic balance towards the procoagulant phase through lowering the TFPI
      levels secreted by the endothelium.

PMID- 10946092
TI  - Comparison of the effect of histidine-rich glycoprotein and 6-aminohexanoic acid
      on plasmin production and fibrinolysis in vitro.
AB  - Because histidine-rich glycoprotein binds to the kringle 1-3 domain of
      plasminogen, it may affect fibrinolysis by reducing fibrin-dependent plasmin
      production, and in this way it could be mechanistically analogous to 6
      aminohexanoic acid. We tested this hypothesis by comparing the effects of
      histidine-rich glycoprotein and 6-aminohexanoic acid in an in vitro assay of
      fibrin-dependent plasmin production mediated by tissue plasminogen activator.
      Whereas 1 mM of 6-aminohexanoic acid increased the K(m) of the reaction from
      approximately 0.22 microM to approximately 1.7 microM, 2 microM of histidine-rich
      glycoprotein had no discernible effect. Similar results were obtained in an assay
      based upon fibrin clot lysis. Therefore, we could not document an effect of
      histidine-rich glycoprotein on the rate of fibrin-dependent plasmin production.

PMID- 10946093
TI  - Thrombotic dysfibrinogenemia. Fibrinogen "Caracas V" relation between very tight
      fibrin network and defective clot degradability.
AB  - Fibrinogen Caracas V is a thrombotic dysfibrinogenemia with an Aalpha 532 Ser-
      >Cys mutation characterized by a tight fibrin network formed of thin fibers
      responsible for a less porous clot than a normal one. In the present work,
      fibrinogen Caracas V is further characterized in order to understand the
      relationship between the structural defect and thrombophilia. This thrombotic
      disorder has been attributed to a tight fibrin network responsible for a
      decreased permeation of flow through the clot, leading to defective thrombus
      lysis due to a diminished availability of fibrinolytic enzymes to the inner
      fibrin surface. Correction of clot structure anomaly, by addition of dextran 40
      to fibrinogen before clotting, induces an improvement in fibrin degradation that
      was attributed to an increase in porosity. The pulmonary embolism observed in
      this family has been related to an hyper rigidity of the clot, an anomaly that is
      also corrected by dextran. Furthermore, this abnormal fibrinogen binds more
      albumin than does normal fibrinogen, a phenomenon attributed to the mutation of
      serine in Aalpha-532 by cysteine. Therefore, this fibrinogen shows a striking
      similarity to the fibrinogen Dusart, allowing us to confirm that the alphaC
      terminal part of fibrinogen plays an important role in fibrin structure, and to
      conclude that the anomaly of fibrin network observed in fibrinogen Caracas V is
      responsible for a deficient thrombus lysis.

PMID- 10946094
TI  - Quantitative determination of PEG-hirudin in human plasma using a competitive
      enzyme-linked immunosorbent assay.
AB  - Polyethylene glycol (PEG) coupled r-hirudin mutein is determined by biological
      methods-the coagulation system. In the present study, a competitive enzyme-linked
      immunosorbent assay (ELISA) is described that permits the measurement of PEG r
      hirudin. The ELISA system adopts a rabbit IgG antibody to quantitatively detect
      PEG-hirudin in human plasma. A PEG-hirudin calibration curve ranged from 50 to
      7000 ng/mL. The limit of detection was 87 ng/mL. The intraassay coefficients of
      variation (CV) ranged between 16 and 21%, and interassay CV between 8 and 22% for
      low and high PEG-hirudin concentrations, respectively. The recovery of the
      compound in plasma was between 96 and 111.5%. The interindividual differences
      between 100 and 5000 ng/mL PEG-hirudin were between 12 and 22%. The correlation
      of the concentration of PEG-hirudin determined with the ELISA and the ecarin
      clotting time was r = 0.902. No interactions between unfractionated heparin, low
      molecular-weight heparin, or phenprocoumon and PEG-hirudin were observed in the
      ELISA. Deficiencies of thrombin or antithrombin as well as low, normal, and high
      fibrinogen levels did not interfere with the assay. It is concluded that the
      ELISA determines the concentration of PEG-hirudin and is not influenced by other
      major anticoagulants or by plasma levels of some coagulation proteins.

PMID- 10946096
TI  - Biomechanics of the cervical spine. I: Normal kinematics.
AB  - This review constitutes the first of four reviews that systematically address
      contemporary knowledge about the mechanical behavior of the cervical vertebrae
      and the soft-tissues of the cervical spine, under normal conditions and under
      conditions that result in minor or major injuries. This first review considers
      the normal kinematics of the cervical spine, which predicates the appreciation of
      the biomechanics of cervical spine injury. It summarizes the cardinal anatomical
      features of the cervical spine that determine how the cervical vertebrae and
      their joints behave. The results are collated of multiple studies that have
      measured the range of motion of individual joints of the cervical spine. However,
      modern studies are highlighted that reveal that, even under normal conditions,
      range of motion is not consistent either in time or according to the direction of
      motion. As well, detailed studies are summarized that reveal the order of
      movement of individual vertebrae as the cervical spine flexes or extends. The
      review concludes with an account of the location of instantaneous centres of
      rotation and their biological basis. RELEVANCE: The fact and precepts covered in
      this review underlie many observations that are critical to comprehending how the
      cervical spine behaves under adverse conditions, and how it might be injured.
      Forthcoming reviews draw on this information to explain how injuries might occur
      in situations where hitherto it was believed that no injury was possible, or that
      no evidence of injury could be detected.

PMID- 10946095
TI  - Dietary fish oil reduces microvascular thrombosis in a porcine experimental
      model.
AB  - Microvascular thrombosis plays a significant role in the pathophysiology of
      ischaemic reperfusion injury. A fish oil-supplemented diet containing n-3
      polyunsaturated fatty acids (PUFA) reduces thromboxane A(2) (TxA(2)) synthesis
      and, thus, vasoconstriction and platelet aggregation. The aim of this study was
      to elucidate whether n-3 PUFA in a porcine model of ischaemia and reperfusion
      injury 1) inhibit accumulation of platelets and fibrinogen in ischaemia
      reperfusion injured tissue, 2) prolong the bleeding time, and 3) inhibit TxA(2)
      synthesis. Nine pigs were fed a standard diet supplemented with 7 g n-3 PUFA/day
      for 3 weeks. Nine pigs on the standard diet served as controls. Unilateral
      myocutaneous flaps were exposed to ischaemia for a period of 6 hours.
      Contralateral flaps were nonischaemic. Tissue contents of radioactive-labelled
      platelets and fibrinogen were measured after 4 hours of reperfusion. Platelet
      count, serum TxB(2), and the cutaneous bleeding time were measured before and
      after 3 weeks of diet. In the fish oil group, the accumulation of platelets was
      significantly reduced in all the myocutaneous flaps, except in the ischaemic skin
      part, when compared to control animals. Fibrinogen was significantly reduced in
      nonischaemic flaps, but not in ischaemic flaps. After the feeding period, the
      level of TxB(2) was significantly lowered in the fish oil group (p<0.01). No
      difference in the bleeding time was observed. Thus, dietary supplementation with
      n-3 PUFA inhibits the formation of microvasculatory thrombosis in this model.

PMID- 10946097
TI  - Qualitative analysis of neck kinematics during low-speed rear-end impact.
AB  - OBJECTIVE: To analyze neck kinematics and loading patterns during rear-end
      impacts. DESIGN: The motion of each cervical vertebra was captured using a 250
      frame/s X-ray system during a whole body rear-end impact. These data were
      analyzed in order to understand different phases of neck loading during rear-end
      impact. BACKGROUND: The mechanism of whiplash injury remains largely unknown. An
      understanding of the underlying kinematics of whiplash is crucial to the
      identification of possible injury mechanisms before countermeasures can be
      designed. METHODS: Metallic markers were inserted into the vertebral bodies and
      spinous processes of each of the seven cervical vertebrae. Relative displacement
      time traces between each pair of adjacent cervical vertebrae were calculated from
      X-ray data. Qualitative analyses of the kinematics of the neck at different phase
      of impact were performed. RESULTS: The neck experiences compression, tension,
      shear, flexion and extension at different cervical levels and/or during different
      stages of the whiplash event. CONCLUSIONS: Neck kinematics during whiplash is
      rather complicated and greatly influenced by the rotation of the thoracic spine,
      which occurs as a result of the straightening of the kyphotic thoracic curvature.
      RELEVANCE: Understanding the complicated kinematics of a rear-end impact may help
      clinicians and researchers shed some light on potential mechanisms of whiplash
      neck injury.

PMID- 10946098
TI  - Reproducibility and instrument validity of a new ultrasonography-based system for
      measuring cervical spine kinematics.
AB  - OBJECTIVE: To report instrument validity of CMS 70P, a new ultrasonography-based
      system for spatial kinematic analysis of the spine and its application in
      studying the reproducibility of cervical motion findings in healthy subjects.
      BACKGROUND: Reproducibility of cervical motion has been investigated using
      various instruments and consisting in most cases of short test-retest time
      intervals of between minutes to days. METHODS: Performance of the instrument was
      validated against a digital inclinometer, at ranges of motion compatible with
      actual cervical motion. To study reproducibility, 25 healthy individuals, 22
      women and 3 men aged 26-48 were tested twice within an average time interval of
      3.3 weeks. Performed in the seated position and at a self-determined pace,
      cervical motion was defined in terms of head motion relative to a sternal
      (reference) system, in all six primary motions: flexion, extension, right
      rotation, left rotation, right lateral flexion and left lateral flexion. RESULTS:
      The system exhibited excellent agreement with the digital inclinometer,
      establishing its instrument validity for testing cervical motion. No significant
      differences were indicated between the test and retest for both the net maximal
      displacements and average velocities. The correlation coefficients for the single
      plane motions (e.g. flexion+extension) were higher than those derived for the
      primary motions, and ranged between 0.78 (sagittal plane) and 0.88 (frontal
      plane). The magnitude of the standard error of the measurement reflected the same
      trend with the lowest value recorded for the frontal plane. The self-selected
      velocity at which these motions were performed was similar in the frontal and
      saggital planes but was significantly higher for the transverse plane
      (rotations). CONCLUSIONS: This study indicates that spanned over time intervals
      that are measured in weeks, cervical motion findings derived from the CMS 70P are
      well reproducible. Findings also imply the need for a more stringent control of
      subject positioning and stabilization. RELEVANCE: Reduction of range of motion
      and average is typically observed in various pathologies of the cervical spine
      and is regarded, together with pain, as a major impairment. Therefore, valid
      assessment of cervical motion which is essential for follow-up and treatment
      outcome strongly depends on reproducibility of the findings. This study indicates
      that acceptable reproducibility is maintained over periods of time which are
      clinically meaningful using the system described herewith.

PMID- 10946099
TI  - Optimal sagittal motion axis for trunk extension and flexion tests in chronic low
      back trouble.
AB  - OBJECTIVE: To find the optimal height for sagittal motion axis for trunk strength
      test in chronic low back trouble. DESIGN: Cross-sectional study. BACKGROUND: The
      strength of trunk muscles of low back pain patients is decreased. The measured
      strength depends on the height of the sagittal motion axis but the differences
      between patients and controls are not known. METHODS: 114 (67 female) patients
      with chronic low back trouble are classified according to Quebec Task Force, 50
      (31 female) patients with rheumatic disorder, but without low back trouble, and
      33 (22 female) healthy controls, no appreciable physical differences but clear
      differences in Oswestry score. Isometric trunk extension-flexion test with
      different heights for the pelvic fulcrum. RESULTS: Force decreased in extension,
      increased in flexion, and torque increased both in flexion and extension in every
      group (P<0.001) as the fulcrum was moved caudally. The male controls were
      stronger than patients with low back trouble (P<0.01). The female controls were
      stronger only if the fulcrum was set at the hip joint level (P<0.05). There were
      no differences between patients with rheumatic disorder and low back trouble,
      except in extension if the fulcrum was at the hip joint level (P<0.02).
      CONCLUSIONS: The rotation axis in trunk extension-flexion strength test should be
      set at the level of the hip joint. RELEVANCE: Trunk muscle weakness is a common
      sign of different rheumatic disorders. Proper setting of sagittal motion axis and
      concomitant measurement of trunk and hip extensor or flexor muscles increases the
      specificity of the strength test for low back trouble.

PMID- 10946100
TI  - Regressionally determined vertebral inclination angles of the lumbar spine in
      static lifts.
AB  - OBJECTIVE: Our previous study has developed the non-invasive models to predict
      the vertebral inclination angles by relating the external stick marker angles and
      radiographic measurements during trunk flexion. Based on these models, the
      present study attempted to further predict the inclination angles using
      externally measured body posture (i.e., lumbar posture, trunk flexion angle, knee
      angle) as well as load handling. DESIGN: Prediction models of the vertebral
      inclination angles were developed with a stepwise regression technique. This was
      done by selecting related postural variables as well as load handling as
      predictors. BACKGROUND: The technique of skin-surface stick marker has been
      investigated for measuring vertebral inclination angles. This technique, however,
      is rarely systematically validated by radiographic measurement because of
      concerns over radiation exposure, especially for ergonomical purposes. METHODS:
      Twelve healthy men aged 22-31 years were recruited in the experiment. The angles
      of the vertebral markers and subject's posture were recorded videographically as
      the subject performed a given task. Prediction models were then developed to
      express the relationships between the vertebral inclinations and the lifting
      postures. RESULTS: The prediction models revealed that the lumbar posture
      (lordosis or kyphosis) had a statistically significant effect on these
      inclination angles. Non-linear first-order regression models of the torso angle
      and the pelvic angle were fit to the transformed vertebral inclination angles
      (transformed from external stick marker angle), with resulting R(2) values
      between 0. 86 and 0.92. CONCLUSIONS: These findings indicate that the vertebral
      inclination angles can be calculated easily and with relative accuracy on the
      basis of the externally measured torso and pelvis angles. RELEVANCE: Measurements
      of lumbosacral vertebral inclination angles are important in assessing low back
      stress during lifting. In this study, we used a regression approach to model
      these angles of the lumbar/sacrum spine in different lumbar postures in the
      sagittal plane. Our data suggest that the vertebral inclination angles can be
      calculated easily. These models may be useful to the low back stress evaluation
      and job design through a biomechanical analysis.

PMID- 10946101
TI  - The reproducibility of multi-joint isokinetic and isometric assessments in a
      healthy and patient population.
AB  - DESIGN: Test re-test reliability design. OBJECTIVE: To determine a reproducible
      protocol for lower limb simultaneous multi-joint assessments on a healthy group
      of subjects and a patient group with patellofemoral pain syndrome. BACKGROUND:
      Although single joint assessment with isokinetic dynamometers has been utilised
      for many years in knee rehabilitation, simultaneous multi-joint assessment has
      not attracted comparable attention. METHODS: Twenty healthy volunteers mean age
      30.6 years and 16 patients with patellofemoral pain syndrome mean age 29.6 years
      performed isometric maximum voluntary contractions and concentric isokinetic
      contractions of the lower limb. Data were collected on three separate days for
      resultant extension/flexion peak torque, average power and total work which were
      analysed using intraclass correlation coefficients with a 95% level of
      confidence. RESULTS: In healthy subjects, intraclass correlation coefficients
      estimates were > or =0.75 for isokinetic peak torque and >0.83 for average power
      and total work. The intraclass correlation coefficients estimate for isometric
      peak torque extension was 0.82. In the patient group, intraclass correlation
      coefficients estimates were >0.82 for isokinetic peak torque and > or =0.75 for
      average power and total work. The intraclass correlation coefficients estimate
      for isometric peak torque extension was 0.89. Discarding the first session's data
      for both groups improved the intraclass correlation coefficients estimates for
      virtually all assessments. CONCLUSIONS: This study has demonstrated high
      reproducibility of lower limb multi-joint testing for peak torque, average power,
      and total work on healthy subjects and then has employed the protocol to
      demonstrate similarly high reliability on a patient group. It has also
      highlighted the need for a practice session before the data can be said to be
      reliable. RELEVANCE: Reliability studies often use healthy subject groups, which
      although useful, have limited relevance to patient populations. This study has
      not only gained comprehensive reproducibility data on multi-joint assessment in
      healthy subjects, it has also shown that multi-joint testing can be used safely
      and reliably in patients with patellofemoral pain syndrome. Clinicians may now be
      able to measure objectively lower limb function in this patient group both pre
      and post treatment.

PMID- 10946102
TI  - Effects of changes in cadence, prosthetic componentry, and time on interface
      pressures and shear stresses of three trans-tibial amputees.
AB  - OBJECTIVE: To evaluate the effects of changes in cadence, prosthetic componentry,
      and time on interface pressures and resultant shear stresses in trans-tibial
      amputee case studies. DESIGN: Interface stresses were monitored using custom
      designed instrumentation at 13 sites on three subjects with unilateral trans
      tibial amputation walking with patellar-tendon-bearing prosthetic limbs.
      BACKGROUND: Previous studies suggested that week-to-week residual limb changes
      altered interface stresses more than did alterations in prosthetic alignment. No
      studies investigating effects of changes in cadence or componentry on interface
      stress distributions nor comparing their influence with week-to-week changes have
      been conducted previously. METHODS: Five different prosthetic componentry
      configurations were tested at each of three cadences in four sessions. Data were
      analysed for the magnitudes and timings of peak pressures and resultant shear
      stresses as well as corresponding resultant shear angles. RESULTS: None of the
      three cadences or five componentry configurations consistently induced
      significantly (P<0.05) higher or lower interface stress magnitudes for all
      subjects. However, an Aluminium Pylon/SACH Foot combination compared with an
      AirStance (pneumatic shank)/Seattle LightFoot unit induced later peak interface
      stress timings as a percentage of stance phase. Higher and more frequent
      interface stress changes were seen between the weekly sessions than between
      different cadences or between different componentry configurations. CONCLUSION:
      The amputees' capabilities to compensate for week-to-week residual limb changes
      were less than those for intra-session cadence or componentry alterations.
      RELEVANCE: Results suggest that effective techniques to accommodate week-to-week
      residual limb fluctuations could have a greater impact on maintaining consistent
      interface stress distributions than do adjustments in cadence or componentry.

PMID- 10946103
TI  - Removal of the lateral or medial third of patellar tendon alters the
      patellofemoral contact pressure and area: an in vitro experimental study in dogs.
AB  - OBJECTIVES: To compare patellofemoral contact pressure and areas after immediate
      removal of the lateral, central, or medial third of patellar tendon. DESIGN: In
      vitro experiment in 12 dogs. BACKGROUND: Alteration of the vector sum of the
      quadriceps muscle contraction after removal of partial patellar tendon might
      result in changes of patellar tracking in the trochlea. METHODS: Patellofemoral
      contact pressure and areas were recorded using Fuji pressure-sensitive film at 45
      degrees, 60 degrees, and 90 degrees of knee flexion under an isometric quadriceps
      force of 100% body weight. The patellofemoral contact imprint from the intact
      knees were obtained as control, and the lateral (n=4), central (n=4), and medial
      (n=4) third of the patellar tendon were subsequently removed and the
      patellofemoral contact imprint was recorded. RESULTS: The patellofemoral contact
      area was found to increase with increasing knee flexion angles. No change in
      patellofemoral contact pressure and areas was found after removal of the central
      third patellar tendon. However, after removal of either lateral or medial third
      of patellar tendon, the patellofemoral contact was rotated with increasing knee
      flexion angles. This was due to the altered vector sum of the quadriceps force,
      resulting in significantly decreased patellofemoral contact areas and
      simultaneously a significantly increased contact pressure, characterized with
      concentration of patellofemoral contact pressure on both lateral and medial
      facets of the patellofemoral joint. CONCLUSIONS: The results suggest that removal
      of the central third of patellar tendon may not alter the patellofemoral contact
      pressure and areas as compared with removal of either lateral or medial third of
      patellar tendon that may result in an altered postoperative tracking mechanism of
      the patellofemoral joint immediately after operation. RELEVANCE: Findings of this
      in vitro animal study supports the use of central third of patellar tendon as
      autograft for anterior cruciate ligament reconstruction. However, further
      experimental studies are needed to investigate how the postoperative healing of
      the host patellar tendon will influence the findings obtained from this in vitro
      study.

PMID- 10946104
TI  - Regulation of rDNA transcription in plastids of higher plants.
AB  - Plastid rDNA expression changes with plastid differentiation, plant development
      and plant growth conditions. Plastid rDNA operons are preceded by different
      promoter structures that are recognised by different types of RNA polymerase in a
      species-specific and development-dependent manner. Present knowledge on
      regulation of rDNA transcription obtained with plant material corresponding to
      different developmental stages and/or different plant species is summarised.
      Results indicate the creation of new and unique transcriptional regulatory
      mechanisms during the evolutionary integration process of the cyanobacterial
      ancestor into the present-day multi-cellular organism.

PMID- 10946105
TI  - The role of sigma factors in plastid transcription.
AB  - Expression of plastid genes is controlled at both transcriptional and post
      transcriptional levels in response to developmental and environmental signals. In
      many cases this regulation is mediated by nuclear-encoded proteins acting in
      concert with the endogenous plastid gene expression machinery. Transcription in
      plastids is accomplished by two distinct RNA polymerase enzymes, one of which
      resembles eubacterial RNA polymerases in both subunit structure and promoter
      recognition properties. The holoenzyme contains a catalytic core composed of
      plastid-encoded subunits, assembled with a nuclear-encoded promoter-specificity
      factor, sigma. Based on examples of transcriptional regulation in bacteria, it is
      proposed that differential activation of sigma factors may provide the nucleus
      with a mechanism to control expression of groups of plastid genes. Hence, much
      effort has focused on identifying and characterizing sigma-like factors in
      plants. While fractionation studies had identified several candidate sigma
      factors in purified RNA polymerase preparations, it was only 4 years ago that the
      first sigma factor genes were cloned from two photosynthetic eukaryotes, both of
      which were red algae. More recently this achievement has extended to the
      identification of families of sigma-like factor genes from several species of
      vascular plants. Now, efforts in the field are directed at understanding the
      roles in plastid transcription of each member of the rapidly expanding plant
      sigma factor gene family. Recent results suggest that accumulation of individual
      sigma-like factors is controlled by light, by plastid type and/or by a particular
      stage of chloroplast development. These data mesh nicely with accumulating
      evidence that the core sigma-binding regions of plastid promoters mediate
      regulated transcription in response to light-regime and plastid type or
      developmental state. In this review I will outline progress made to date in
      identifying and characterizing the sigma-like factors of plants, and in
      dissecting their potential roles in chloroplast gene expression.

PMID- 10946106
TI  - Sense from nonsense: how the genetic information of chloroplasts is altered by
      RNA editing.
AB  - Plastid transcripts can be subject to an RNA processing mechanism changing the
      identity of individual nucleotides and thus altering the information content of
      the mRNA. This processing step was termed RNA editing and adds a novel mechanism
      to the multitude of RNA maturation events required before mRNAs can serve as
      faithful templates in plastid protein biosynthesis. RNA editing in chloroplasts
      proceeds by the conversion of individual cytidine residues to uridine and, in
      some bryophytes, also by the reverse event, uridine-to-cytidine transitions. The
      discovery of RNA editing in chloroplasts has provided researchers with a wealth
      of molecular and evolutionary puzzles, many of which are not yet solved. However,
      recent work employing chloroplast transformation technologies has shed some light
      on the molecular mechanisms by which RNA editing sites are recognized with
      extraordinarily high precision. Also, extensive phylogenetic studies have
      provided intriguing insights in the evolutionary dynamics with which editing
      sites may come and go. This review summarizes the state-of-the-art in the field
      of chloroplast RNA editing, discusses mechanistic and evolutionary aspects of
      editing and points out some of the important open questions surrounding this
      enigmatic RNA processing step.

PMID- 10946107
TI  - Participation of nuclear genes in chloroplast gene expression.
AB  - The expression of the plastid genome is dependent on a large number of nucleus
      encoded factors. Some of these factors have been identified through biochemical
      assays, and many others by genetic screens in Arabidopsis, Chlamydomonas and
      maize. Nucleus-encoded factors function in each step in plastid gene expression,
      including transcription, RNA editing, RNA splicing, RNA processing, RNA
      degradation, and translation. Many of the factors discovered via biochemical
      approaches play general roles as components of the basic gene expression
      machinery, whereas the majority of those identified by genetic approaches are
      specifically required for the expression of small subsets of chloroplast genes
      and are involved in post-transcriptional steps. Some of the nucleus-encoded
      factors may play regulatory roles and modulate chloroplast gene expression in
      response to developmental or environmental cues. They may also serve to couple
      chloroplast gene expression with the assembly of the protein products into the
      large complexes of the photosynthetic apparatus. The convergence of biochemical
      approaches with those of classical and reverse genetics, and the contributions
      from large scale genomic sequencing should result in rapid advances in our
      understanding of the regulatory interactions that govern plastid gene expression.

PMID- 10946108
TI  - Processing and degradation of chloroplast mRNA.
AB  - The conversion of genetic information stored in DNA into a protein product
      proceeds through the obligatory intermediate of messenger RNA. The steady-state
      level of an mRNA is determined by its relative synthesis and degradation rates,
      i.e., an interplay between transcriptional regulation and control of RNA
      stability. When the biological status of an organism requires that a gene
      product's abundance varies as a function of developmental stage, environmental
      factors or intracellular signals, increased or decreased RNA stability can be the
      determining factor. RNA stability and processing have long been known as
      important regulatory points in chloroplast gene expression. Here we summarize
      current knowledge and prospects relevant to these processes, emphasizing
      biochemical data. The extensive literature on nuclear mutations affecting
      chloroplast RNA metabolism is reviewed in another article in this volume (Barkan
      and Goldschmidt-Clermont, this issue).

PMID- 10946109
TI  - Translation in chloroplasts.
AB  - The discovery that chloroplasts have semi-autonomous genetic systems has led to
      many insights into the biogenesis of these organelles and their evolution from
      free-living photosynthetic bacteria. Recent developments of our understanding of
      the molecular mechanisms of translation in chloroplasts suggest selective
      pressures that have maintained the 100-200 genes of the ancestral endosymbiont in
      chloroplast genomes. The ability to introduce modified genes into chloroplast
      genomes by homologous recombination and the recent development of an in vitro
      chloroplast translation system have been exploited for analyses of the cis-acting
      requirements for chloroplast translation. Trans-acting translational factors have
      been identified by genetic and biochemical approaches. Several studies have
      suggested that chloroplast mRNAs are translated in association with membranes.

PMID- 10946110
TI  - Assembly of chloroplast cytochromes b and c.
AB  - The synthesis of holocytochromes in plastids is a catalyzed process. Several
      proteins, including plastid CcsA, Ccs1, possibly CcdA and a thioredoxin, plus at
      least two additional Ccs factors, are required in sub-stoichiometric amounts for
      the conversion of apocytochromes f and c(6) to their respective holoforms. CcsA,
      proposed to be a heme delivery factor, and Ccs1, an apoprotein chaperone, are
      speculated to interact physically in vivo. The formation of holocytochrome b(6)
      is a multi-step pathway in which at least four, as yet unidentified, Ccb factors
      are required for association of the b(H) heme. The specific requirement of
      reduced heme for in vitro synthesis of a cytochrome b(559)-derived holo-beta(2)
      suggests that cytochrome b synthesis in PSII might also be catalyzed in vivo.

PMID- 10946111
TI  - Synthesis, assembly and degradation of thylakoid membrane proteins.
AB  - The thylakoid membrane of chloroplasts contains four major protein complexes,
      involved in the photosynthetic electron transfer chain and in ATP synthesis.
      These complexes are built from a large number of polypeptide subunits encoded
      either in the nuclear or in the plastid genome. In this review, we are
      considering the mechanism that couples assembly (association of the polypeptides
      with each other and with their cofactors) with the upstream and downstream steps
      of the biogenetic pathway, translation and proteolytic degradation. We present
      the contrasting images of assembly that have emerged from a variety of approaches
      (studies of photosynthesis mutants, developmental studies and direct biochemical
      analysis of the kinetics of assembly). We develop the concept of control by
      epistasy of synthesis, through which the translation of certain subunits is
      controlled by the state of assembly of the complex and address the question of
      its mechanisms. We describe additional factors that assist in the integration and
      assembly of thylakoid membrane proteins.

PMID- 10946112
TI  - Chloroplast site-directed mutagenesis of photosystem I in Chlamydomonas: electron
      transfer reactions and light sensitivity.
AB  - The photosystem I (PSI) complex is a multisubunit protein-pigment complex
      embedded in the thylakoid membrane which acts as a light-driven
      plastocyanin/cytochrome c(6)-ferredoxin oxido-reductase. The use of chloroplast
      transformation and site-directed mutagenesis coupled with the biochemical and
      biophysical analysis of mutants of the green alga Chlamydomonas reinhardtii with
      specific amino acid changes in several subunits of PSI has provided new insights
      into the structure-function relationship of this important photosynthetic
      complex. In particular, this molecular-genetic analysis has identified key
      residues of the reaction center polypeptides of PSI which are the ligands of some
      of the redox cofactors and it has also provided important insights into the
      orientation of the terminal electron acceptors of this complex. Finally this
      analysis has also shown that mutations affecting the donor side of PSI are
      limiting for overall electron transfer under high light and that electron
      trapping within the terminal electron acceptors of PSI is highly deleterious to
      the cells.

PMID- 10946113
TI  - Chloroplast proteases: possible regulators of gene expression?
AB  - A wide range of proteolytic processes in the chloroplast are well recognized.
      These include processing of precursor proteins, removal of oxidatively damaged
      proteins, degradation of proteins missing their prosthetic groups or their
      partner subunit in a protein complex, and adjustment of the quantity of certain
      chloroplast proteins in response to changing environmental conditions. To date,
      several chloroplast proteases have been identified and cloned. The chloroplast
      processing enzyme is responsible for removing the transit peptides of newly
      imported proteins. The thylakoid processing peptidase removes the thylakoid
      transfer domain from proteins translocated into the thylakoid lumen. Within the
      lumen, Tsp removes the carboxy-terminal tail of the precursor of the PSII D1
      protein. In contrast to these processing peptidases which perform a single endo
      proteolytic cut, processive proteases that can completely degrade substrate
      proteins also exist in chloroplasts. The serine ATP-dependent Clp protease,
      composed of the proteolytic subunit ClpP and the regulatory subunit ClpC, is
      located in the stroma, and is involved in the degradation of abnormal soluble and
      membrane-bound proteins. The ATP-dependent metalloprotease FtsH is bound to the
      thylakoid membrane, facing the stroma. It degrades unassembled proteins and is
      involved in the degradation of the D1 protein of PSII following photoinhibition.
      DegP is a serine protease bound to the lumenal side of the thylakoid membrane
      that might be involved in the chloroplast response to heat. All these peptidases
      and proteases are homologues of known bacterial enzymes. Since ATP-dependent
      bacterial proteases and their mitochondrial homologues are also involved in the
      regulation of gene expression, via their determining the levels of key regulatory
      proteins, chloroplast proteases are expected to play a similar role.

PMID- 10946114
TI  - Genetic engineering of the chloroplast.
AB  - Transformation of the plastid genome has a number of inherent advantages for the
      engineering of gene expression in plants. These advantages include: 10-50 times
      higher transgene expression levels; the absence of gene silencing and position
      effect variation; the ability to express polycistronic messages from a single
      promoter; uniparental plastid gene inheritance in most crop plants that prevents
      pollen transmission of foreign DNA; integration via a homologous recombination
      process that facilitates targeted gene replacement and precise transgene control;
      and sequestration of foreign proteins in the organelle which prevents adverse
      interactions with the cytoplasmic environment. It is now 12 years since the first
      conclusive demonstration of stable introduction of cloned DNA into the
      Chlamydomonas chloroplast by the Boynton and Gillham laboratory, and 10 years
      since the laboratory of Pal Maliga successfully extended these approaches to
      tobacco. Since then, technical developments in plastid transformation and
      advances in our understanding of the rules of plastid gene expression have
      facilitated tremendous progress towards the goal of establishing the chloroplast
      as a feasible platform for genetic modification of plants.

PMID- 10946115
TI  - Flixborough revisited - an explosion simulation approach.
AB  - A literature study of explosion estimation reports from the Flixborough accident
      was performed and commented. The results from this survey were compared to the
      results obtained from explosion simulations. The simulations were done with a
      computer model of the Flixborough plant using the EXSIM software simulation tool.
      The comparison showed that explosion magnitude estimates in the literature based
      on visual inspection are much lower than the simulated results, while the
      estimates based on calculations to a large degree conform with the simulations.
      The simulations also showed that the exact location of the ignition source does
      not seem to be significant for the magnitude of the explosion.

PMID- 10946116
TI  - Some aromatic nitrate esters: synthesis, structural aspects, thermal and
      explosive properties.
AB  - 1-(2-Nitroxyethylnitramino)-2,4,6-trinitrobenzene (I-A), 1, 3-bis(2
      nitroxyethylnitramino)-2,4,6-trinitrobenzene (II-A) and 1,3, 5-tris(2
      nitroxyethylnitramino)-2,4,6-trinitrobenzene (III-A) have been prepared by
      condensing picryl chloride, styphnyl chloride and 1, 3,5-trichloro-2,4,6
      trinitrobenzene with ethanol amine, respectively, followed by nitration. These
      compounds have been characterized by infrared spectrum (IR), the elemental
      analysis and 1H NMR. Further, these compounds have been studied for their thermal
      and explosive properties. The activation energy of thermal decomposition of these
      compounds has also been determined using the Ozawa and the Kissinger methods. The
      data on explosive properties indicate that the impact, friction and velocity of
      detonation (VOD) increase with an increase in the number of nitrate ester groups.

PMID- 10946117
TI  - Tantalum dust deflagration in a bag filter dust-collecting device.
AB  - An accidental tantalum powder deflagration with casualties occurred during the
      operation of a bag filter dust-collecting device. To understand the mechanism of
      the incident and its material hazards, experiments for determining the
      combustibility and ignition characteristics of the tantalum powder were
      performed. The magnitude of the tantalum dust explosion is classified as severe
      (K(st)=273), contrary to the classification found in the preceding literature.
      The minimum ignition energies for both a dust cloud and a dust layer of the
      tantalum powder were also found to be far lower than previous values. Judging
      from the observation of the surface with an SEM, the coral-like structure of each
      particle of the tantalum powder can enhance its fire and explosion hazards and
      affect its sensitivity to electrostatic sparks by increasing in particle surface
      area. A thin, non-conductive oxide layer of the tantalum powder surface has a
      high resistivity and generates electrostatic charge when rubbed with conductive
      materials like the wall of the collecting device. The authors conclude that the
      possible cause of the ignition was electrostatic discharge resulting from
      charging electrostatically.

PMID- 10946118
TI  - A study of the behaviour of a protected vessel containing LPG during pool fire
      engulfment.
AB  - Theoretical and experimental investigations of various methods for protection
      against fires of vessels containing liquefied petroleum gases (LPG) (safety
      relief valves, intumescent fire retardant coatings, thermal isolation) have been
      carried out. A simple mathematical model has been proposed, which describes
      dependences of various parameters on time. These parameters are temperature,
      pressure and mass of LPG, temperatures of the vessel's walls and thermal
      protection layer. The case of total fire engulfment of the vessel with LPG was
      considered. Experiments have been executed, which were aimed on the investigation
      of the behaviour of vessels with LPG (50 l), equipped with protective devices
      during total fire engulfment. It was found out that the safety valve prevented an
      explosion of the vessels without any other protective measures. The presence of
      the intumescent fire retardant coating caused a significant delay in operation of
      the safety valve. A rather good agreement between the theoretical and
      experimental data was obtained. It has been revealed that the considered methods
      for protection of LPG vessels are promising in regard to prevention of explosions
      in these vessels at the fire engulfment.

PMID- 10946119
TI  - Analysis of data from spilling experiments performed with liquid hydrogen.
AB  - This work describes the modelling of liquid hydrogen release experiments using
      the ADREA-HF 3-D time dependent finite volume code for cloud dispersion, jointly
      developed by DEMOKRITOS and JRC-Ispra. The experiments were performed by Batelle
      Ingenieurtechnik for BAM (Bundesanstalt fur Materialforschung und Prufung),
      Berlin, in the frame of the Euro-Quebec-Hydro-Hydrogen-Pilot-Project and they
      mainly deal with LH2 near ground releases between buildings. In the present
      study, the experimental trial #5 was assumed for simulation due to the fact that
      in this release the largest number of sensor readings were obtained. The
      simulations illustrated the complex behaviour of LH2 dispersion in presence of
      buildings, characterized by complicated wind patterns, plume back flow near the
      source, dense gas behaviour at near range and significant buoyant behaviour at
      the far range. The simulations showed the strong effect of ground heating in the
      LH2 dispersion. The model also revealed major features of the dispersion that had
      to do with the "dense" behaviour of the cold hydrogen and the buoyant behaviour
      of the "warming-up" gas as well as the interaction of the building and the
      release wake. Such a behaviour was in qualitative and even quantitative agreement
      with the experiment. The results are given in terms of concentration time series,
      scatter plots, contour plots, wind field vector plots and 3-D concentration
      wireframes. Given all experiment uncertainties, the model gives reasonable
      results on concentrations levels.

PMID- 10946120
TI  - The influence of heavy metals on partitioning of PAHs during incineration.
AB  - The presence of heavy metals (Cr, Cd, Pb and Zn) in feedstock increases the
      partitioning of polycyclic aromatic hydrocarbons (PAHs) in the solid as well as
      in the gaseous phases, which has been reported in our previous study. However,
      the partitioning of PAHs in air-pollution control equipment (APCE) has not been
      investigated thus far. Hence, the present work was conducted to study the
      partitioning of PAHs in APCE and the effect of heavy metals on PAHs formation by
      varying the target heavy metals in the feedstock.A fluidized bed incineration
      system which includes a primary combustion chamber (sand bed), a secondary
      combustion chamber (freeboard), and an APCE (cyclone and scrubber) was utilized
      in this study. The feedstock that contained various heavy metals was fed into the
      incinerator, and then the PAHs in the cyclone and scrubber were analyzed to
      determine the effect of heavy metals on PAHs partitioning. The results indicate
      that the presence of Pb and Zn in feedstock facilitates the formation of PAHs.

PMID- 10946121
TI  - Framework for the environmental damage assessment of an industrial process chain.
AB  - On the basis of the life cycle approach, a framework for the assessment of the
      environmental damages generated by an industrial process chain is established. In
      order to consider all the processes of the life cycle, a methodology is developed
      based on an eco-matrix formed by chemical process eco-vectors containing all
      their environmental loads. To perform the impact assessment, environmental damage
      indicators are estimated in the most accurate way possible for each process. For
      this, site-specific evaluation is carried out applying damage functions and,
      hence, for each damage indicator, a damage matrix is obtained. In order to make
      the methodology more practical, options like dominance analysis are presented.
      Because of the large number of environmental loads, the focus is on the priority
      pollutants and then the final estimations are done with one indicator per
      safeguard subject. The damage indicators selected in this paper are damage costs,
      ecological damage parameter (both site-specific) and global damage estimates. As
      for the verification of the methodology, a study has been carried out based on
      the life cycle of the electricity produced by a municipal waste incinerator.

PMID- 10946122
TI  - Toxic byproducts from the combustion of varnish wastes based on polyurethane in a
      laboratory furnace.
AB  - Varnish wastes based on polyurethane were burnt in a laboratory scale furnace at
      different residence time of gases and temperatures and with a fuel-rich
      atmosphere and with an excess of oxygen. The yields of CO, CO(2), six light
      hydrocarbons (methane, ethylene, etc. ) and 31 semivolatile+volatile compounds
      (benzene, toluene, naphthalene, dibezofuran, etc.) were determined with
      stoichiometric factors of the oxygen between 0.6 and 0.9, nominal temperatures of
      the reactor between 750-1050 degrees C and residence times of the volatiles
      evolved and formed between 2 and 6 s. The collection of the volatiles evolved was
      carried out with a Tedlar bag and by XAD-4 resin, comparing the data obtained in
      both cases. The maximum emission factors or yields of volatiles+semivolatiles
      were obtained at 850-950 degrees C, with values above 0.5% for benzene,
      naphthalene, acenaphthylene, phenantrene and fluoranthene. The thermal behaviour
      of different compounds was analysed. Naphthalene, benzene and toluene were also
      detected in the excess oxygen runs.

PMID- 10946123
TI  - Highly crystalline faujasitic zeolites from flyash.
AB  - The process for the synthesis of flyash-based zeolites (FAZs) are presented,
      which basically includes alkaline treatment of flyash by a fusion method,
      followed by hydrothermal crystallization. Zeolite-Y has been identified, and
      conditions have been optimized for their synthesis by the fusion method. Optimal
      conditions for synthesis of Zeolite-Y are a NaOH/flyash ratio of 1.2:1, fusion
      temperature between 500 degrees C and 600 degrees C, crystallization time of 8-10
      h and crystallization temperature between 100 degrees C and 110 degrees C. The
      cation exchange capacity (CEC) of FAZ-Y ranges between 400 and 450 meq/100 g. The
      surface area of FAZs (500-600 m(2)/g) compare well with the commercial zeolites
      procured from Mobil Oil. Morphological characterization of FAZ using scanning
      electron microscopy (SEM) reveals cubic structure, and XRD data reveal unit cells
      to be cubic system.

PMID- 10946124
TI  - Development of a biofilm formation method for waste forms stability evaluation.
AB  - The development of an accurate assessment protocol is critical for the prediction
      of long-term performance of waste disposal systems under field conditions. In
      this study, the development of a biofilm formation method for the evaluation of
      waste forms stability to microbially induced degradation (MID) is reported. The
      development process involved significant modifications to the existing Nuclear
      Regulatory Commission (NRC) approach. In the biofilm formation method, the
      control media and fermenter broths are designed to be of similar pH to avoid
      overestimation of the microbe's capability to degrade the waste forms. In the NRC
      approach, the pH values are different. The existing one-stage process of the NRC
      approach is also replaced with a two-stage process in the biofilm formation
      method. This is to ensure full evaluation of the microbe's involvement in waste
      forms degradation. The first stage of the two-stage process is for biofilm
      formation and the second is for biofilm evaluation. The use of a two-stage
      process eliminates the possibility of substrate limitation, resulting in values
      of degradation indices that are about two times higher than those obtained using
      the single-stage NRC approach. Two waste forms (100% Tuskegee cement and 21%
      cobalt chloride/79% cement) were used in the development of the biofilm formation
      method. Both waste forms showed evidence of biofilm formation. The formation of
      biofilm on the cobalt-containing waste form indicates a lack of anti-microbial
      capability of cobalt.

PMID- 10946125
TI  - Compost produced from organic fraction of municipal solid waste, primary
      stabilized sewage sludge and natural zeolite.
AB  - The aim of this work is to present the physicochemical characteristics of the
      compost produced from dewatered anaerobically stabilized primary sewage sludge
      (DASPSS), organic fraction of municipal solid waste (OFMSW) and the metal uptaken
      by zeolite (clinoptilolite). The final results indicated that the composted
      material produced from clinoptilolite 20% w/w and 80% w/w DASPSS and OFMSW (60%
      and 40%, respectively) provided better soil conditioning compared to the compost
      produced from DASPSS. The co-composting products had a higher concentration of
      total humic and organic matter (O.M.) than the sewage sludge compost. Also, the
      heavy metals concentration in the final products was in lower concentration than
      in the sewage sludge compost. The zeolite appeared to uptake a significant
      (p<0.05) amount of metals. Specifically, the use of 20-25% w/w of clinoptilolite
      appears to uptake 100% of Cd, 10-15% of Cr, 28-45% of Cu, 41-47% of Fe, Mn 9-24%
      of Mn, 50-55% of Ni and Pb, and 40-46% of Zn. Although by the application of the
      composting process, the reduction in dry mass is between 30% and 40% for all
      samples.

PMID- 10946126
TI  - Feasibility of electrokinetic soil remediation in horizontal Lasagna cells.
AB  - An integrated soil remediation technology called Lasagna has been developed that
      combines electrokinetics with treatment zones for use in low permeability soils
      where the rates of hydraulic and electrokinetic transport are too low to be
      useful for remediation of contaminants. The technology was developed by two
      groups, one involving industrial partners and the DOE and another involving US
      EPA and the University of Cincinnati, who pursued different electrode geometries.
      The Industry/DOE group has demonstrated the technology using electrodes and
      treatment zones installed vertically from the soil surface. We have demonstrated
      the feasibility of installing horizontal electrodes and treatment zones in
      subsurface soils by hydraulic fracturing, a process that we adapted from
      petroleum industry practices. When horizontal electrodes were connected to a dc
      power supply, uniform electrical potential gradients of 10-40 V/m were created in
      soil between the electrodes, inducing electroosmotic flow that facilitated
      movement of water and contaminants into treatment zones between the electrodes.

PMID- 10946127
TI  - The use of municipal sewage sludge for the stabilization of soil contaminated by
      mining activities.
AB  - The ability of municipal sewage sludge to immobilize Pb, Zn and Cd contained in
      contaminated soil originating from a former mining area in Lavrion, Greece was
      investigated. The soil was cured with sewage sludge in various proportions. The
      stabilization was evaluated primarily by applying chemical tests and complemented
      by the performance of additional biological tests. Application of the U.S. EPA
      Toxicity Characteristic Leaching Procedure (TCLP) on the stabilized mixtures
      proved that Pb, Zn and Cd solubility was reduced by 84%, 64% and 76%,
      respectively, at 15% w/w sludge addition, while a 10% w/w addition was sufficient
      to reduce Pb solubility below the U.S. EPA TCLP regulatory limit. The results of
      the extraction using EDTA solution showed the same trend, resulting in 26%, 36%
      and 53% reduction in the Pb, Zn and Cd extractable fractions, respectively.
      Speciation analysis of the treated soils revealed a significant decrease in the
      mobile fractions of heavy metals, which was attributed to their retention in
      sewage sludge by adsorption and organic complexation mechanisms. For the
      assessment of possible phytotoxicity, experiments including growing dwarf beans
      in the treated soil was carried out. It was found that sewage sludge addition had
      a positive effect on plant growth. Furthermore, the Pb and Zn uptake of plant
      leaves and roots was reduced, while Cd uptake was unaffected by the sludge
      treatment. The results of this study support the hypothesis that municipal sewage
      sludge is a potential effective stabilizing agent for contaminated soil
      containing Pb, Zn and Cd.

PMID- 10946128
TI  - Modeling the kinetics of UV/hydrogen peroxide oxidation of some mono-, di-, and
      trichlorophenols.
AB  - The decomposition of a number of chlorophenols (CPs), namely 2-CP, 2, 4
      dichlorophenol and 2,4,6-trichlorophenol, has been studied in aqueous solution by
      UV-catalyzed oxidation with H(2)O(2) under UV radiation emitted by a 125-W medium
      pressure Hg lamp in an immersion well-type quartz photoreactor, and the organic
      bound chlorine has been converted into the environmentally harmless inorganic
      chloride. For oxidant/CP mole ratios between 1:1 and 16:1, the reaction kinetics
      were modeled and the corresponding rate constants found by periodically measuring
      the remaining CP, hydrogen peroxide and converted chloride in solution. A
      theoretical model for the degradation pathway is proposed expressing the rate as
      a linear function of the concentrations of CP and oxidant. The rate constants for
      the pseudo-first order approximation of the CP degradation were compared.
      H(2)O(2), when combined with UV, is an effective photoactivated oxidant. The
      photodegradation order in terms of the initial rate of CPs destruction was:
      Cl(3).Ph>/=Cl(2).Ph>Cl.Ph.

PMID- 10946129
TI  - Solidification and stabilization of asbestos waste from an automobile brake
      manufacturing facility using cement.
AB  - Currently, the generated brake lining waste dust, which contains asbestos as its
      major component, is disposed of into a secure landfill without any additional
      treatment. As an alternative to this, solidification/stabilization (S/S) disposal
      of the dust was investigated using Portland cement alone and Portland cement
      mixed with activated carbon (AC), as the binders. Toxicity Characteristics
      Leaching Procedure (TCLP) results on the solidified matrix showed that cement was
      able to immobilize the heavy metals, Ba, Zn, Cr, Pb, Cu and Fe, to within the
      limits set by the US EPA for TCLP. Addition of AC to the cement reduced the
      leaching of heavy metals by an additional 4-24% compared to cement alone. The pH
      of the TCLP leachate extracted from virgin cement, and from dust treated with
      cement with or without AC was found to increase to 10.9-12.5 as opposed to an
      initial value of 4.93 for the TCLP extract for the untreated dust. Results of ANS
      16.1 (modified) leach protocol revealed that Ba in cement-treated samples showed
      the highest leach rate, followed by Zn, Pb, Cr, Cu and Fe. The leach rate of
      heavy metals decreased with progress in time. Cement mixed with AC exhibited
      similar leach characteristics, however, the leach rate was lower. The linear
      relationship between the cumulative fraction leached (CFL) and the square root of
      leaching time in all cement-based samples indicate that a diffusional process is
      the controlling transport mechanism for the leaching of the heavy metals. The
      obtained Leachability Indices (L(i)) of 7.6-9.1 and 8.3-9.5 for cement and cement
      with AC, respectively, were low but exceeded the guidance value of 6, which
      clearly indicates that all the heavy metals studied are retained well within
      solid matrices. Cement-based S/S hardening times increased from 30 to 96 h as the
      dust content increased from 40 to 70 wt.%. The resulting solid matrices exhibited
      a compressive strength ranging from 1 to 12 MPa, which was well above the
      specified limit of 414 kPa for such matrices. An economic analysis indicates that
      the disposal costs for the dust in the only available secure landfill would
      increase by 40.3% if one were to go for the cement S/S option. Addition of AC to
      the cement would escalate this by an additional 43.8%. Although the S/S of brake
      lining dust using cement effectively immobilized the heavy metals of concern,
      cost considerations may hinder the commercial adaptation of this technique for
      waste disposal unless new regulatory demands are implemented.

PMID- 10946130
TI  - A new method to control electrolytes pH by circulation system in electrokinetic
      soil remediation.
AB  - To simultaneously avoid a decrease of electro-osmotic flow by hydrogen ions and
      to increase heavy metal precipitation due to hydroxide ions, simulated
      electrokinetic remediation was conducted in saturated kaolinite specimens loaded
      with lead(II) using an electrolyte circulation method to control electrolyte pH.
      At an electrolyte circulation rate of 1.1 ml/min, it was possible to increase the
      anolyte pH from 2 to 4 and decrease the catholyte pH from 12 to 8. Using
      electrolyte circulation, it was observed that the rate of decrease of clay pH due
      to the change of electrolyte pH was reduced. As a result, the operable period was
      extended and the removal efficiency for lead(II) was also increased. It was
      observed that most of the effluent lead(II) from the cathode compartment was
      electroplated onto the cathode and that residual effluent lead(II) did not
      precipitate onto, or adsorb to, the clay at the anode compartment during
      circulation. Therefore, there was no need to treat the electrolyte because there
      was virtually no effluent from the cathode compartment in the circulation system.
      It was also found that the electrolyte volume required to sustain the
      electrolytic reaction was sufficient for the whole electrokinetic remediation
      process.

PMID- 10946131
TI  - Disposal of arsenic in copper discharge slags.
AB  - Arsenic, which is a toxic pollutant, is present in copper minerals in
      concentrations to around 1 wt.%. During processing of such copper feed materials,
      the arsenic has to be transformed into an environmentally acceptable form.
      Laboratory experiments have been carried out to determine the feasibility of
      incorporating the arsenic in discharge slags for long-term disposal. Iron
      arsenate (FeAsO(4)) samples were prepared and tested under various conditions.
      Upon heating to about 900 degrees C, basically no arsenic was lost. However, at
      and above 1000 degrees C, iron arsenate decomposes rapidly and arsenic
      volatilizes. The incorporation of iron arsenate in liquid slags at around 1250
      degrees C was difficult due to rapid arsenate decomposition and dust losses
      during the injection process. Although the leaching tests showed that the slags
      could meet environmental regulations, the fraction of arsenic leached was no less
      for the slag samples than for the initial iron arsenate itself.

PMID- 10946132
TI  - Comparison of serological tests for Trypanosoma evansi natural infections in
      water buffaloes from north Vietnam.
AB  - In the present study, a collection of 415 water buffalo serum samples originating
      from the north of Vietnam was used for evaluation of different diagnostic
      antibody detection methods available to detect infections with Trypanosoma
      evansi. The diagnostic sensitivity and specificity of a direct card agglutination
      test (CATT/T. evansi), an indirect card agglutination test (LATEX/T. evansi) and
      a newly developed antibody detection ELISA (ELISA/T. evansi) was calculated on
      the basis of parasitological results, obtained by mouse inoculation, and compared
      for all assays. The immume trypanolysis assay with the predominant T. evansi
      RoTat 1.2 variable antigen type was used as reference test for antibody presence.
      All parasitologically confirmed animals (n=8) were positive in all tests.
      Diagnostic specificity was highest in CATT/T. evansi (98%) followed by the
      ELISA/T. evansi (95%) and the LATEX/T. evansi (82%). Concordance of the variant
      specific immune trypanolysis test with the other tests was calculated and
      revealed that few (1-8%) false positive results were actually due to a specific
      reactions, and that LATEX/T. evansi and ELISA/T. evansi detected more immune
      trypanolysis positives than the CATT/T. evansi. It was concluded that, apart from
      the immune trypanolysis test, which is not generally applicable, ELISA/T. evansi
      with a 30% positivity cut-off and LATEX/T. evansi, thanks to their superior
      capacity of detecting T. evansi specific antibodies, would be suitable as
      epidemiological tools detecting both active infections and persisting T. evansi
      specific antibodies. The ELISA/T. evansi with a 50% positivity cut-off and the
      CATT/T. evansi on the other hand, seem more appropriate to detect true infected
      water buffaloes.

PMID- 10946133
TI  - The use of entomopathogenic fungi for the control of parasitic mites, Psoroptes
      spp.
AB  - In vitro trials were carried out to evaluate the potential of fungal pathogens as
      biological control agents of parasitic mites, Psoroptes ovis (Hering) (Acari:
      Psoroptidae) from rabbit hosts (synonym: Psoroptes cuniculi). The fungus
      Hirsutella thompsonii Fisher showed no pathogenicity. Metarhizium anisopoliae
      (Metschinkoff), however, showed a high level of pathogenicity; 3 days after
      exposure to fungal conidia all mites were dead and 6 days after exposure 60% of
      the dead adult females, 10% of the dead adult males and 30% of the dead female
      nymphs had fungal hyphae protruding from their cuticular surface. There was a
      significant effect of conidial concentration on the number of mite cadavers that
      displayed fungal infection. Exposure to between 1x10(4) and 1x10(6) conidiaml(-1)
      resulted in 2-25% of the mites being infected. Mean infection levels were
      highest, 71%, when the mites were exposed to 1x10(7) conidiaml(-1). Similarly,
      there was a significant effect of conidial concentration on the time taken for
      the mites to reach 50% levels of mortality (LT(50)) The mean LT(50) value was
      approximately 2.7 days, when the mites were exposed to a solution of 1x10(7) and
      1x10(8) conidiaml(-1) which was significantly shorter than controls exposed to
      0.03% Tween-80 solution only. There was no significant effect of passaging the
      fungus, either once or twice, through the host on the subsequent infectivity of
      M. anisopliae. The potential for use of entornopathogenic fungi for the control
      of parasitic mites, particularly in relation to sheep, is discussed.

PMID- 10946134
TI  - Biological and biochemical characterization of isolates of Trypanosoma evansi
      from Pantanal of Matogrosso--Brazil.
AB  - Ten isolates of Trypanosoma evansi from the Pantanal region of Brazil, recently
      derived from coati (Nasua nasua, carnivora, Procyonidae), horses and dogs, were
      characterized on the basis of biological (experimental infections in Wistar rats)
      and biochemical (multilocus enzyme eletrophoresis) data. Biological data were
      analyzed by Nested analysis of variance and Kruskal-Wallis. Marked heterogeneity
      in virulence was observed in the isolates. Some of the isolates showed an
      undulating parasitaemia, typical for African trypanosomes. This biological
      heterogeneity did not correspond with the biochemical homogeneity observed in the
      T. evansi isolates. T. evansi has one of the widest distributions and greatest
      range of mammalian hosts and is widely recognized to have evolved from
      Trypanosoma brucei. Adaptability of T. evansi was not reflected in the
      variability of biochemical and molecular parameters studied to date. The
      variability in virulence was very significant, but not correlated with the host
      from which it was derived. These data suggested that, in the region studied, T.
      evansi is transmitted among both domestic and sylvatic animals in one single
      transmission cycle.

PMID- 10946135
TI  - Neospora hughesi: experimental infections in mice, gerbils, and dogs.
AB  - Neospora hughesi is a recently described cause of equine protozoal
      myeloencephalitis (EPM). A rodent model for pathogenicity would facilitate
      development of therapies to be used in horses. In the present study, we examined
      the susceptibility of BALB/c gamma-interferon gene knockout (gamma-INFKO),
      BALB/c, CD-1, and C57BL/6 strains of mice and gerbils to infection with
      tachyzoites of the Nh-A1 strain of N. hughesi isolated from a horse from AL, USA.
      Only the gamma-IFNKO mice developed severe clinical disease following infection
      with N. hughesi and died 19-25 days after infection and exhibited severe cardiac
      lesions. In contrast, experimental infection of gamma-INFKO mice with tachyzoites
      of the NC-1 or NC-Liverpool strains of Neospora caninum resulted in deaths 8-10
      days after infection. The most severe lesions were in the livers, spleens, and
      lungs of these mice. Gerbils inoculated with N. hughesi did not develop clinical
      disease, had few microscopic lesions, but did seroconvert. Two dogs fed the
      brains of mice, shown to contain N. hughesi tissue stages by cell culture and
      gamma-IFNKO mouse bioassay, did not shed N. caninum-like oocysts over a 23 days
      observation period. The marked difference in pathogenicity between the two
      species of Neospora in gamma-IFNKO mice, and lack of oocyst excretion by dogs fed
      N. hughesi infected mice provide additional evidence that the species distinction
      between N. caninum and N. hughesi is valid.

PMID- 10946136
TI  - Reduction in tick numbers (Haemaphysalis longicornis), mortality and incidence of
      Theileria sergenti infection in field-grazed calves treated with flumethrin pour
      on.
AB  - The effectiveness of the pour-on formulation of flumethrin was tested on grazing
      cattle. Flumethrin was applied once a month from April to October from 1990 to
      1995 to cattle grazing in the Aso area of Kumamoto Prefecture in Japan. Both the
      number of ticks in the field and the number of ticks feeding on cattle decreased
      remarkably in relation to the number of years flumethrin was applied. Ticks in
      the field were not detected in 1994 and 1995, and ticks feeding on cattle
      decreased to 4% in 1995. Mortality due to Theileria sergenti infection also
      decreased significantly after more than 3 years of flumethrin pour-on
      application, although overall mortality did not change. At the end of the trial
      the incidence of T. sergenti had decreased to one-fifth of the pretrial value,
      although total incidence of disease had not changed. These results indicated that
      multiple-year seasonal application of flumethrin pour-on to grazing cattle
      effectively decreased the number of ticks and decreased both mortality and
      incidence of T. sergenti.

PMID- 10946137
TI  - Simulation of rotational grazing to evaluate integrated pest management
      strategies for Boophilus microplus (Acari: ixodidae) in Venezuela.
AB  - Ranchers in Venezuela historically have controlled the cattle-fever tick,
      Boophilus microplus (Canestrini), with acaricide treatments of cattle but no
      technical planning. We developed a simulation model to evaluate cattle-tick
      population dynamics in systematic pasture rotation systems and Integrated Pest
      Management (IPM) approaches to managing ticks in the tropical dry-forest
      ecological zone of Venezuela. Model output showed five generations of cattle
      ticks produced each year throughout the dry and rainy seasons that occur in this
      zone. Sensitivity analyses showed disproportionately large changes in on-host B.
      microplus populations in response to small changes in larval mortality rates,
      such as those resulting from differences in the innate resistance of cattle to
      tick parasitism. Simulation results with 1-6 pasture systems suggest that
      adjusting the graze:rest sequence with systematic rotation among 4-6 pastures
      could suppress, but not eradicate, tick populations.

PMID- 10946138
TI  - Infection rate of Ehrlichia risticii, the agent of Potomac horse fever, in
      freshwater stream snails (Juga yrekaensis) from northern California.
AB  - Juga yrekaensis freshwater snails were tested for trematode stages and for
      Ehrlichia risticii DNA using a nested PCR assay. Snails were collected monthly
      from two Potomac horse fever (PHF) endemic locations in northern California
      (Montague and Weed). The trematode infection rate varied between 40 and 93.3% in
      large snails (shell size >15mm) and between 0 and 13.3% in small snails (<15mm).
      The highest trematode infection rate for large and small snails was recorded in
      September and the lowest infection rate for large snails was recorded in June
      (Weed) and October (Montague). The E. risticii PCR infection rate among small
      snails from both sites was similar and varied monthly between 0 and 3.3%. The PCR
      infection rate for large snails from Weed was high in May (20.0%) and decreased
      progressively until November (10.0%). The PCR infection rate for large snails
      from Montague was 5.0% in May, 26.3% in August and 16. 7% in October. PCR
      positive snails were always related to the microscopic detection of trematode
      stages (virgulate cercariae). This study provides evidence that J. yrekaensis are
      infected with trematode cercariae that harbor E. risticii. The number of snails
      harboring trematode stages and the number of PCR positive snails varied with the
      size of the snails, the month of collection, and the geographic origin.

PMID- 10946139
TI  - Inoculation of Sarcocystis neurona merozoites into the central nervous system of
      horses.
AB  - Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from
      the Americas and is usually caused by infection with the apicomplexan parasite,
      Sarcocystis neurona. A horse model of EPM is needed to test the efficacy of
      chemotherapeutic agents and potential vaccines. Five horses that were negative
      for antibodies to S. neurona in their serum and cerebrospinal fluid (CSF) were
      injected in the subarachnoid space with living merozoites of the SN2 isolate of
      S. neurona. None of the horses developed clinical disease or died over a 132-day
      observation period. All five horses developed antibodies to S. neurona in their
      CSF and serum 3-4 weeks after injection. Two of the horses were examined at
      necropsy and no parasite induced lesions were observed in their tissues and no
      parasites were recovered from portions of their spinal cords inoculated on to
      cell cultures. Results of this study demonstrate that merozoites of the SN2
      isolate of S. neurona will induce seroconversion but not clinical disease when
      inoculated directly into the CSF of nonimmune horses.

PMID- 10946140
TI  - Determination of the activity of ponazuril against Sarcocystis neurona in cell
      cultures.
AB  - The present study examined the efficacy of ponazuril in inhibiting merozoite
      production of Sarcocystis neurona in cell cultures. Ponazuril inhibited merozoite
      production by more that 90% in cultures of S. neurona treated with 1.0 microg/ml
      ponazuril and greater than 95% inhibition of merozoite production was observed
      when infected cultures were treated with 5.0 microg/ml ponazuril. Ponazuril may
      have promise as a therapeutic agent in the treatment of S. neurona induced equine
      protozoal myeloencephalitis (EPM) in horses.

PMID- 10946141
TI  - Validation of a reverse transcriptase multiplex PCR test for the serotype
      determination of U.S. isolates of bluetongue virus.
AB  - Bluetongue (BT) is an arthropod-borne viral disease affecting ruminants primarily
      in tropical and temperate regions of the world. Of the 24 serotypes of BT virus
      (BTV) identified worldwide, five have been found in the United States. Serotype
      identification of BTV isolates is important to the epidemiology of the virus, but
      current methods are cumbersome. A single-tube multiplex reverse transcriptase
      polymerase chain reaction (mRT-PCR) assay, previously developed for the serotype
      determination of U.S. BTV isolates, was evaluated. The determination of serotype
      was based on the size of the resultant amplified product. The procedure was
      evaluated using all 24 serotypes of BTV and nine serotypes of epizootic
      hemorrhagic disease virus (EHDV), a closely related orbivirus. Only the five U.S.
      serotypes of BTV were detected by the mRT-PCR. The assay was further tested using
      132 BTV isolates originating from 24 western and southern states of the United
      States, from several different host species, spanning a period of 24 years. The
      serotypes of the isolates were determined by both a virus neutralization (VN)
      procedure and the mRT-PCR. Comparison of the mRT-PCR to the standard VN showed
      that the mRT-PCR successfully identified the serotypes of 130 of the isolates and
      was shown to be more reliable and specific than the VN assay.

PMID- 10946142
TI  - Equine herpesvirus 1 (EHV-1) glycoprotein D DNA inoculation in horses with pre
      existing EHV-1/EHV-4 antibody.
AB  - We have shown previously that equine herpesvirus 1 (EHV-1) glycoprotein D (gD)
      DNA elicited protective immune responses against EHV-1 challenge in murine
      respiratory and abortion models of EHV-1 disease. In this study, 20 horses, all
      with pre-existing antibody to EHV-4 and two with pre-existing antibody to EHV-1,
      were inoculated intramuscularly with three doses each of 50, 200 or 500microg EHV
      1 gD DNA or with 500microg vector DNA. In 8 of 15 horses, inoculation with EHV-1
      gD DNA led to elevated gD-specific antibody and nine horses exhibited increased
      virus neutralising (VN) antibody titres compared to those present when first
      inoculated. A lack of increase in gC-specific antibody during the 66 weeks of the
      experiment showed that the increase in gD-specific antibodies was not due to a
      natural infection with either EHV-1 or EHV-4. The increase in EHV-1 gD-specific
      antibodies was predominantly an IgGa and IgGb antibody response, similar to the
      isotype profile reported following natural EHV-1 infection.

PMID- 10946143
TI  - Co-administration of IL-2 enhances antigen-specific immune responses following
      vaccination with DNA encoding the glycoprotein E2 of bovine viral diarrhoea
      virus.
AB  - Induction of effective immunity requires the delivery of a protective antigen
      with appropriate co-stimulatory signals. For bovine viral diarrhoea virus (BVDV)
      this antigen is the major viral glycoprotein E2. Neutralising antibodies are
      directed towards the E2 protein and passive transfer of antibodies in serum or
      colostrum can completely protect against viral infection. DNA vaccination of mice
      with a construct encoding the E2 glycoprotein induced neutralising antibody
      levels that were potentially sufficient to prevent virus replication in a
      challenge system. The co-delivery of interleukin-2 (IL-2) further enhanced the
      levels of antibody raised. The strong IgG2a component of the antigen-specific
      antibody suggests a Th1 bias to the immune response induced following
      vaccination.

PMID- 10946144
TI  - Prevalence of Salmonella in beef feeder steers as determined by bacterial culture
      and ELISA serology.
AB  - Results are presented for monitoring Salmonella infection by bacteriological
      culture and immune response (enzyme linked immunosorbent assay (ELISA) and
      haptoglobin) testing of samples collected from beef cattle at a single feedyard
      sampled over time. A total of 120 beef steers were examined on entry to the
      feedyard and at days 30, 60, and at time of slaughter (120-150 days). Isolations
      of Salmonella decreased over time from 40% of the steers sampled at day 0 to 0%
      at slaughter, whereas serological results varied by serogroup. Seropositivity
      increased for Salmonella group B up to day 60, and subsequently decreased to
      about half of the 60-day positivity rate at the time of slaughter. No significant
      changes in seropositivity were detected during the course of the study for the
      four other Salmonella serogroups (C1, C3, D1, and E1). Haptoglobin measurements
      were not a good indicator of Salmonella infection status. Sequential Salmonella
      testing either by culture, ELISA, or both could be used to monitor pathogen
      control practices.

PMID- 10946145
TI  - Differences between Danish bovine and human Staphylococcus aureus isolates in
      possession of superantigens.
AB  - PCR-assays for the detection of staphylococcal enterotoxins A-E, and H, toxic
      shock toxin 1, and exfoliative toxins A and B were evaluated against phenotypic
      methods, and performed well. Four hundred and fourteen isolates of Staphylococcus
      aureus from Danish cases of bovine mastitis were screened for genes encoding
      these superantigens. One hundred isolates from Danish human carriers were also
      included in the study. In contrast to the frequent presence of genes encoding and
      in vitro expression of superantigens among the human carrier isolates, only one
      of 414 isolates from bovine mastitis carried the genes encoding enterotoxin C and
      toxic shock toxin-1. These results further support the hypothesis that the bovine
      and human S. aureus reservoirs constitute two separate sub-populations of the
      species S. aureus. The results also show that these superantigens are generally
      not present in Danish S. aureus isolates from bovine mastitis, and thus play no
      essential role in the pathogenesis of bovine S. aureus mastitis.

PMID- 10946146
TI  - Novel fimbrial subunit genes of Dichelobacter nodosus: recombination in vivo or
      in vitro?
AB  - Polymerase chain reaction (PCR) was used to amplify the variable region of the
      fimbrial subunit encoding gene (fimA) of Dichelobacter nodosus from sheep and
      goats infected with footrot. Two amplimers (designated X and Y) generated single
      strand conformation polymorphism (SSCP) patterns different to those of previously
      identified serogroups and serotypes. DNA sequencing revealed that these two
      fragments were novel. The upstream of X (nt 1-183) was identical to serotype M1
      while its downstream (nt 223-414) was identical to serotype F1; the upstream of Y
      (nt 1-116) was identical to serotype E1, whereas its downstream (nt 148-423) was
      identical to serotype F1. A 14-mer sequence consisting of two partially
      overlapping Chi-like sequences, 5'-GCTGGTGCTGGTGA-3', was also found in these
      fragments. Two primer sets with the downstream primer specific for serotype F1
      and the upstream primer specific for serotype M or E1, generated PCR products of
      the expected sizes from the footrot samples from which fragments X and Y were
      isolated, respectively. These primer sets did not appear to amplify artificially
      mixed genomic DNA from serotypes M and F1 or E1 and F1. However, when the
      reactions were re-amplified, PCR recombination artifacts were observed,
      suggesting that PCR recombination does occur, but at a low frequency. It,
      therefore, seems more likely that fragments X and Y reflect genuine fimA genes of
      D. nodosus which have resulted from in vivo DNA recombination rather than from a
      PCR recombination artifact.

PMID- 10946147
TI  - The afa-related gene cluster in necrotoxigenic and other Escherichia coli from
      animals belongs to the afa-8 variant.
AB  - Six hundred and nine necrotoxigenic Escherichia coli type 1 and 2 (NTEC1 and
      NTEC2) and non-NTEC isolated in Western and Southern Europe, North Africa and
      Canada from diseased calves, pigs, humans, poultry, and 55 isolated from
      asymptomatic calves were studied for the identification of afa-related sequences
      to the recently described afa-7 and afa-8 gene cluster variants from two bovine
      Escherichia coli (Lalioui et al., 1999). Colony hybridization and PCR assays for
      the afaD-7, afaE-7, afaD-8 and afaE-8 identified the afa-related sequences to the
      afa-8 gene cluster in most (67/79; 85%) of the E. coli positive with the Afa-f
      family probe and in 14 additional strains negative with the Afa-f probe. No E.
      coli was positive for the afa-7 gene cluster. The existence of afa-8 positive
      strains was thus confirmed among bovine E. coli and for the first time among
      porcine, poultry and human E. coli. Sequencing of the afaE-8 amplicon of nine
      strains from the different host species showed a high degree of conservation
      (>95% at the DNA level; >92% at the amino-acid level). The afa-8 gene cluster was
      more frequent in E. coli from diseased calves (18%) than from piglets (12%),
      humans (6%) and poultry (5%). Bovine NTEC2 (26%) were more frequently positive
      than NTEC 1 (20%) and non-NTEC (11%). E. coli isolated from asymptomatic calves
      were rarely positive: one NTEC2 (3%) and no non-NTEC. The afa-8 gene cluster was
      located on the Vir plasmid in 11/23 NTEC2, but no plasmid localization was
      detected in NTEC1 or non-NTEC.

PMID- 10946148
TI  - Orally administered attenuated Salmonella enteritidis reduces chicken cecal
      carriage of virulent Salmonella challenge organisms.
AB  - Chickens were immunized orally with 10(9)cfu of the temperature-sensitive (T(s))
      mutant E/1/3 of Salmonella enteritidis at 1, 2, 3 and 7 days of age. The animals
      were challenged with wild-type strains of Salmonella of different serotypes 7 or
      14 days following immunization. Chickens receiving multiple oral doses of the
      vaccine strain showed no signs of disease. Immunized animals shed the vaccine
      strain for at least 2 weeks after the last inoculation; on the other hand,
      colonization by the attenuated mutant of internal organs such as spleen and liver
      was limited. Early exposure of the immunized animals to the virulent bacteria
      resulted in a reduced cecal colonization by the pathogen. Visceral invasion by
      the wild-type strain of S. enteritidis or S. gallinarum was drastically
      diminished in birds challenged 14 days after immunization. Significant
      differences in the number of these Salmonella were found in the cecal contents,
      spleen and liver of immunized birds compared with the control animals. In
      addition, cecal colonization by the virulent strain was reduced in birds
      challenged with S. typhimurium. These results demonstrate that immunization of
      newly hatched chickens with live attenuated T(s) mutant E/1/3 of S. enteritidis
      is safe and reduces Salmonella shedding.

PMID- 10946149
TI  - Humoral immune response of BALB/c mice to a vaccinia virus recombinant expressing
      Brucella abortus GroEL does not correlate with protection against a B. abortus
      challenge.
AB  - This work is a part of an ongoing effort to develop vaccinia virus recombinants
      expressing various Brucella abortus proteins. The B. abortus groEL gene encoding
      the antigenic heat shock protein GroEL was subcloned into vaccinia virus via
      homologous recombination and expression confirmed by Western blotting. Female
      BALB/c mice inoculated with recombinant vaccinia virus/GroEL produced GroEL and
      vaccinia virus specific antibodies. Mice were challenged 8 weeks post-inoculation
      with virulent B. abortus strain 2308 and protection measured by the rate of
      clearance of live Brucella from spleens. Although induction of specific immune
      response to GroEL and vaccinia virus was demonstrated by the appearance of
      antibodies in mice, no significant level of protection was demonstrable.

PMID- 10946150
TI  - First isolation of Exophiala dermatitidis from a dog: identification by molecular
      analysis.
AB  - The present study deals with the first isolation of Exophiala dermatitidis from a
      dog. The dog had a history of multicentric lymphoma for 4 months. On physical
      examination, 10-15 black or purple subcutaneous nodules were detected on the
      dorsum of the right neck. Microscopic examination of biopsy specimen from the
      nodules disclosed lymphocytes, neutrophils and moniliform hyphae. The colony of
      the clinical isolate was flat with black aerial hyphae and a wet margin after 2
      weeks incubation on Sabouraud's dextrose agar at 27 degrees C. The microscopic
      examination of the clinical isolate revealed that hyphae were brown, septate, and
      smooth, producing branched or unbranched conidiospores laterally or on the apex.
      The conidia were one celled, subglobose, elliptical to cylindrical, smooth and
      hyaline. Nucleotide sequence analysis of the chitin synthase 2 (CHS2) gene
      fragments from the isolate and a reference strain of E. dermatitidis showed more
      than 99% similarity.

PMID- 10946152
TI  - Effects of chronic prenatal ethanol exposure on hippocampal glutamate release in
      the postnatal guinea pig.
AB  - This study was designed to test the hypothesis that chronic prenatal ethanol
      exposure decreases basal and stimulated L-glutamate release in the hippocampus of
      young, postnatal guinea pigs. Timed, pregnant guinea pigs were randomly assigned
      to one of the following three chronic treatment groups: 4 g ethanol/kg maternal
      body weight/day, isocaloric-sucrose and pair-feeding to the ethanol group, and
      water. Each oral treatment was given daily throughout gestation. Spontaneous
      locomotor activity was increased on postnatal day (PD) 10, and brain and
      hippocampal weights were decreased on PD 12 in the offspring of the ethanol group
      compared with the isocaloric-sucrose/pair-fed and water groups. On PD 12, the 45
      mM K(+)- and 10 microM veratridine-stimulated release of glutamate in transverse
      hippocampal slices was decreased in the ethanol group compared with the two
      control groups. This alteration in glutamate release produced by chronic prenatal
      ethanol exposure may decrease the efficiency of excitatory synaptic transmission
      in the hippocampus during postnatal life.

PMID- 10946153
TI  - Effects of ritanserin on ethanol withdrawal-induced anxiety in rats.
AB  - This study investigated the ability of ritanserin, a 5-HT2 antagonist, to modify
      ethanol withdrawal (EW) symptoms in two animal models of anxiety: the elevated
      plus-maze (EPM) and the pentylenetetrazol (PTZ) discrimination assay. Long-Evans
      hooded rats were given a nutritionally balanced liquid diet containing 4.5%
      ethanol for 10 days. Twelve hours after removal of the ethanol diet, rats were
      tested in the EPM. A significant reduction in the open-arm activity and the
      number of total arm entries was observed, which is indicative of EW. Acute
      ritanserin (0.16-0.64 mg/kg, i.p., 60 min) had no effect on EW-induced anxiety
      like behavior on the EPM. Ritanserin (0.08-0.64 mg/kg, i.p., b.i.d. 12 h)
      administered concurrently with the last 5 days of ethanol diet produced an
      increase in the time spent on the open arms of the EPM and reversed the EW
      induced reduction in total arm entries. Rats trained to discriminate between
      saline and PTZ (an anxiogenic drug), selected the PTZ lever during EW. Chronic
      ritanserin (0.32 mg/kg, i.p., b.i.d. ) did not block PTZ lever responding during
      EW. On the rotorod, ritanserin (0.32 mg/kg, i.p.) increased the motor
      incoordination induced by ethanol. In conclusion, coadministration of ritanserin
      with ethanol prevented the development of EW-induced anxiety as measured by the
      EPM, but not in the PTZ drug discrimination.

PMID- 10946154
TI  - Metabolism of some radiolabeled essential fatty acids in isolated rat hepatocytes
      is affected by dietary ethanol.
AB  - The metabolism of the essential fatty acids [1-14C]20:4n-6, [1-14C]20:5n-3 and [1
      14C]22:6n-3 was studied in rat hepatocytes fed ethanol in two different diets.
      Using a diet with a low lipid content ethanol (1) reduced the elongation of
      eicosapentaenoic acid, (2) reduced the esterification of docosahexaenoic acid
      (DHA) in phospholipids (PL), (3) increased the oxidation of DHA, (4) increased
      the ratio of esterification of DHA in phosphatidylethanolamine (PE) compared to
      phosphatidylcholine (PC) (PE/PC ratio), (5) altered the formation of PL molecular
      species, and (6) induced a decrease in the endogenous content of the hepatocytes
      of arachidonic acid and linoleic acid and an increase in oleic acid, 20:3n-9 and
      DHA. Using a high lipid diet, only the above-mentioned effect (4) was induced by
      ethanol, not the effects (1)-(3) and (5)-(6).

PMID- 10946155
TI  - Lipopolysaccharide tolerance and ethanol modulate hepatic nitric oxide production
      in a gender-dependent manner.
AB  - This study was directed at the role of tolerance to endotoxin
      (lipopolysaccharide, LPS) and ethanol (EtOH) intoxication in modulating hepatic
      nitric oxide (NO) production, and the demonstration of gender differences.
      Previous studies demonstrated that tolerance to either LPS or EtOH was associated
      with reduced hepatic production of superoxide anions. We now tested the
      hypothesis that the reduced hepatic production of superoxide anions during
      tolerance to LPS and the altered response to EtOH are accompanied by increased
      sensitivity of hepatic NO release to stimulation. Age-matched male and female
      Sprague-Dawley rats were made tolerant to LPS by an i.v. injection of LPS (0.5 or
      0.45 mg/kg) 2 days prior to an in vivo EtOH infusion for 3 h (LPS-EtOH group).
      Control groups were saline-pretreated, saline-infused; saline-pretreated, EtOH
      infused; and LPS-pretreated, saline-infused. At the end of the infusion, isolated
      hepatocytes, Kupffer, and sinusoidal endothelial cells were cultured for 20 h for
      subsequent measurement of basal (spontaneous) and in vitro-stimulated nitrite
      release. LPS-tolerance resulted in significantly enhanced stimulated NO
      production by hepatocytes and Kupffer cells in both male and female rats. EtOH
      abolished this priming effect in hepatocytes from male, but not from female rats.
      The priming effect was markedly diminished by EtOH in Kupffer cells of female
      rats only. LPS-tolerance increased NO production by stimulated endothelial cells
      of males, and decreased NO production by cells of females. EtOH infusion did not
      influence NO production by endothelial cells from male rats and it reversed the
      LPS-tolerance-induced inhibition in females. These data demonstrate that
      modulation by LPS-tolerance of hepatic NO release in EtOH-treated rats leads to
      enhanced stimulated NO production, while hepatic superoxide anion release was
      previously shown to be reduced within the same time frame. Since NO is able to
      scavenge superoxide, the LPS-tolerance-induced alterations in the EtOH effects on
      NO production may have a potential significance in modulating - in a time
      dependent manner - oxidative injury associated with LPS and acute EtOH intake.

PMID- 10946156
TI  - Peripheral involvement in nicotine-induced enhancement of ethanol intake.
AB  - It is a well-known fact that a large percentage of alcoholics smoke, and in the
      experimental rat, intermittent nicotine administration enhances ethanol intake
      and ethanol preference in a free-choice situation between 6% (v/v) ethanol and
      water. The present study focuses on the possible involvement of central and/or
      peripheral nicotine acetylcholine receptors (nAChR) in nicotine-induced
      sensitization to dopamine-related behavioral effects of ethanol. Wistar rats
      drinking less than 60% of their total daily fluid from a 6% ethanol solution were
      used in the study. Nicotine, vehicle, mecamylamine, hexamethonium,
      mecamylamine+nicotine, and hexamethonium+nicotine were administered
      subchronically for 15 days. All groups, except the vehicle pre-treated group,
      markedly increased their ethanol preference to approximately 80%, as well as
      their ethanol intake. NMRI mice received the same treatments for 10 days, after
      which ethanol (2.5 g/kg, intraperitoneal (i.p.)) was given acutely and locomotor
      activity was recorded. Ethanol-induced locomotor stimulation was enhanced in most
      groups, as compared to the vehicle pre-treated group. Administration of
      quarternary autonomic drugs to ethanol high-preferring rats (hexamethonium,
      methscopolamine, sotalol and phentolamine) according to different acute and
      chronic treatment protocols indicated that the enhanced ethanol intake may
      involve increased ganglionic and/or peripheral muscarinic neurotransmission.
      Taken together, the above results indicate that peripheral mechanisms may be
      involved in the enhancement of dopamine-related behavioral effects of ethanol
      observed after subchronic intermittent treatment with nicotinic drugs.

PMID- 10946157
TI  - Effect of neonatal ethanol exposure on parvalbumin-expressing GABAergic neurons
      of the rat medial septum and cingulate cortex.
AB  - This study was performed to determine the long-term effects of ethanol exposure
      during the brain growth spurt (postnatal days 4-10) on the number of parvalbumin
      immunoreactive (PA+) GABAergic neurons in the adult (P60) rat medial septum and
      anterior cingulate cortex. Significant loss of neurons within each of these
      populations has previously been demonstrated following prenatal ethanol exposure.
      In the present study, no significant differences in the number of PA+ neurons
      were found in either the medial septum or the cingulate cortex when control and
      ethanol-exposed animals were compared. The cellular densities and volumetric
      measures in both brain regions were also similar in the two groups. We speculate
      that compensatory up-regulative mechanisms may have accounted for the protection
      of the PA neuronal populations in these two areas following the early neonatal
      exposure.

PMID- 10946158
TI  - Development of short-lasting alcohol deprivation effect in sardinian alcohol
      preferring rats.
AB  - Alcohol deprivation effect (ADE), defined as a temporary increase in voluntary
      alcohol intake following a period of alcohol abstinence, was evaluated in
      selectively bred Sardinian alcohol-preferring (sP) rats. Alcohol was initially
      offered in free choice with water for 35 consecutive days (predeprivation phase).
      Subsequently, one group of rats was deprived of alcohol for 1, 3, 7, 15, 30, 90
      or 180 consecutive days, while the second group had continuous access to alcohol
      (deprivation phase). Once alcohol was re-presented, alcohol intake in alcohol
      deprived rats was recorded 1 and 24 h after alcohol re-presentation and compared
      to that monitored in alcohol-nondeprived rats over the same time periods
      (postdeprivation phase). Alcohol deprivation for 3 to 30 days resulted in a
      significant increase in voluntary alcohol intake only in the first hour of re
      access. These results demonstrate the development of ADE in sP rats. However, the
      rapid return of alcohol intake to control levels is discussed as evidence in
      favor of a set-point mechanism capable of regulating alcohol-drinking behavior in
      sP rats.

PMID- 10946159
TI  - Prenatal alcohol exposure increases TNFalpha-induced cytotoxicity in primary
      astrocytes.
AB  - We examined the effect of prenatal alcohol exposure (PAE) on tumor necrosis
      factor-alpha-(TNFalpha) induced cell death in primary astrocyte cultures. Flow
      cytometry revealed that PAE increased the sensitivity of astrocytes to the
      cytotoxic effects of TNFalpha when compared to astrocytes prepared from pair-fed
      and chow-fed controls. In a number of cell types, TNFalpha regulates cell growth
      or death, in part, by the hydrolysis of sphingomyelin to ceramide and sphingosine
      1-phosphate (SPP). Using a 3-(4. 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) cytotoxic assay we found that PAE increased the sensitivity of
      astrocytes to the cytotoxic effects of TNFalpha, sphingomyelinase (SMase), and
      C(2)- and C(6)-ceramide. The increasing cellular concentrations of SPP, a
      sphingolipid metabolic that induces cell growth, protected the cells from
      TNFalpha-induced cell death. N, N-dimethylsphingosine (DMS), which inhibits SPP
      production, and N-oleoylethanolamine, which inhibits acid ceramidases, increased
      TNFalpha-induced cytotoxicity in astrocytes prepared from PAE rats. These studies
      suggest that PAE shifts the balance of sphingolipid metabolism in favor of a
      pathway that increases the susceptibility of astrocytes to the cytotoxic effect
      of TNFalpha.

PMID- 10946160
TI  - Effects of 5-HT(3) receptor antagonists on daily alcohol intake under
      acquisition, maintenance, and relapse conditions in alcohol-preferring (P) rats.
AB  - Previous research indicated that 5-HT(3) antagonists can reduce ethanol drinking
      in rats, but drinking conditions and other environmental manipulations influenced
      the efficacy of these antagonists. The current experiments were conducted to
      examine the effects of the 5-HT(3) antagonists MDL 72222 (MDL) or ICS 205-930
      (ICS) on 24-h ethanol (10% v/v) consumption during acquisition, maintenance, and
      following a period of deprivation in selectively bred high alcohol-preferring (P)
      male rats. In an analysis of the acquisition of ethanol consumption, daily
      injections of MDL (1 mg/kg; s.c.) or ICS (1 or 5 mg/kg) were administered to
      separate groups of P rats during the initial 10 days of ethanol exposure. To
      examine the maintenance of ethanol drinking, these same groups of rats were
      allowed access to ethanol for 21 days with no pharmacological manipulations, and
      were then administered either saline or the 5-HT(3) antagonist. To examine the
      effects of a 5-HT(3) antagonist on relapse of ethanol drinking, another group of
      P rats was allowed access to ethanol for 6 weeks and was then deprived of ethanol
      for 3 weeks. Prior to ethanol reinstatement, rats were treated chronically (seven
      daily injections) or acutely with MDL (1 mg/kg), saline, or received no
      injections. MDL (1 mg/kg) and ICS (1 or 5 mg/kg) reduced ethanol intake during
      acquisition (60-80%) and during maintenance drinking (35-70%) in P rats
      pretreated with saline during acquisition. However, in rats pretreated with MDL
      or ICS during acquisition, there was a significant reduction in the effectiveness
      of either MDL or ICS to reduce ongoing ethanol drinking. Neither acute nor
      chronic treatment with 1 mg/kg MDL altered the 80% increase in ethanol
      consumption observed on the first day of reinstatement following a 3-week
      deprivation period. However, in a follow-up study, acute treatment with MDL (3
      mg/kg) or ICS (5 mg/kg) did prevent the 80% increase in ethanol consumption
      observed on the first day of reinstatement. Overall, the results suggest that 5
      HT(3) receptors are involved in the acquisition and maintenance of 24-h ethanol
      drinking, and that neuroadaptations may occur as a result of chronic treatment
      with 5-HT(3) antagonists, or during prolonged alcohol deprivation, which alter
      the involvement of these receptors in regulating alcohol drinking in the P rat.

PMID- 10946161
TI  - Mechanisms of suppression of poly I:C-induced activation of NK cells by ethanol.
AB  - We have previously reported that ethanol (EtOH) decreases polyinosinic
      polycytidylic acid (poly I:C) and interleukin-2 (IL-2)-induced upregulation of
      natural killer (NK) cell lytic activity in mice. The present study was designed
      to determine if decreased production of or response to interferon-alpha (IFN
      alpha) is involved and if this is associated with inhibited upregulation of
      perforin or granzyme B. Treatment of mice with poly I:C upregulated IFN-alpha and
      granzyme B, but not perforin, in the spleen. Administration of EtOH before poly
      I:C prevented the upregulation of IFN-alpha and granzyme B and decreased perforin
      levels. EtOH exposure in vivo rendered splenocytes less able to respond to IFN
      alpha upon in vitro exposure to poly I:C. Exogenous IFN-alpha only partially
      prevented this decreased response. Thus, decreased production of and response to
      IFN-alpha as well as decreased levels of granzyme B and perforin are implicated
      in the diminished activation of NK cell lytic function in EtOH-treated mice.

PMID- 10946162
TI  - Effects of prior ethanol exposure on ethanol self-administration in a continuous
      access situation using retractable drinking tubes.
AB  - To examine whether exposure to ethanol influences subsequent ethanol consumption
      using a continuous access procedure, two groups of rats were given differing
      initial exposure to ethanol. One group underwent a sucrose-substitution
      initiation procedure. The second group received abbreviated initiation consisting
      of one-session exposure to each ethanol/sucrose combination used in standard
      initiation. The animals were then provided with 23 h/day access to ethanol (10%,
      v/v) from a retractable drinking tube. Food pellets were available following a
      single-lever press, and water was available from a sipper tube. After 5 weeks,
      the data indicated that few significant differences existed between the groups on
      total ethanol (g/kg), food or water consumed. The overall intake (g/kg/day),
      number of ethanol bouts per day, and amount consumed per bout (g/kg/bout) were
      substantially lower than observed in previous research using ethanol presented in
      a dipper. However, differences in g/kg per ethanol bout did differ significantly
      between the two groups with the group receiving standard initiation showing more
      ethanol consumed per bout. These data agree with our previous work indicating
      that initiation results in larger drinking bouts.

PMID- 10946163
TI  - Cancer pain education: the use of a structured clinical instruction module to
      enhance learning among medical students.
AB  - The Structured Clinical Instruction Module (SCIM) is an educational format
      developed for the teaching of clinical and interpersonal skills. The purpose of
      this study was to develop and pilot-test a SCIM to enhance medical students'
      learning and understanding about cancer pain assessment and management. The
      Cancer Pain SCIM was presented to 34 third-year medical students. Eight
      instructors and six standardized patients (five cancer patients) participated in
      the course. All participants evaluated the course using a five-point Likert scale
      (1 = strongly disagree; 5 = strongly agree). Students self-assessed their
      clinical skills before and after the course using a five-point scale (1 = not
      competent; 5 = very competent). Students agreed [mean (S.D.)] very strongly that
      the SCIM was a valuable educational experience [4.4 (0.56)] and that it was
      beneficial to use actual cancer patients in the SCIM [4.5 (0.63)]. Students
      believed their skills in the assessment and management of cancer pain
      significantly improved after the course. The SCIM is a valuable and novel
      instructional format to teach essential skills in the assessment and management
      of cancer pain to medical students.

PMID- 10946164
TI  - How response shift may affect the measurement of change in fatigue.
AB  - If patients experience extreme fatigue during treatment, they may judge the level
      of fatigue following this experience differently from how they would have judged
      it before. This change in internal standard is referred to as a response shift.
      We explored whether a response shift might have occurred in patients receiving
      radiotherapy (n = 199). Fatigue was assessed before and after radiotherapy.
      Following completion of the post-test, a thentest was administered where patients
      had to provide a renewed judgment of their pre-treatment level of fatigue.
      Response shift was assessed by the mean difference between the pre-test and
      thentest scores. Comparing the thentest with the pretest scores, patients
      retrospectively minimized their pre-treatment level of fatigue. The thentest-post
      test difference was significant, whereas the conventional pretest-post-test
      difference was not. These results are in line with the occurrence of a response
      shift. Additional hypotheses regarding response shift were partially supported.
      It is concluded that the potentially large implications of response shift justify
      further research.

PMID- 10946165
TI  - Effects on cancer patients' health-related quality of life after the start of
      morphine therapy.
AB  - To investigate the effects of morphine on cancer patients' health-related quality
      of life (HRQL), we prospectively studied 40 cancer patients with moderate or
      severe pain despite treatment with "weak" opioids. The patients were titrated to
      pain relief using immediate-release (IR) morphine and then switched to slow
      release (SR) morphine in the same daily dosages. HRQL was measured by the
      European Organization for Research and Treatment of Cancer core quality-of-life
      questionnaire (EORTC QLQ-C30) before the start of morphine (baseline), after
      stabilization with IR-morphine, and 3 days after start of SR-morphine. The mean
      titrated daily morphine dosage was 97 mg (range, 60-180). The EORTC QLQ-C30
      global health score increased after IR morphine titration (baseline score 40, IR
      morphine period score 49), but a significant difference from baseline did not
      persist during the SR morphine period (score 44). The other functional HRQL
      scores showed no significant fluctuations. After start of IR morphine, two of the
      HRQL symptom scores increased, nausea/vomiting and constipation, but these
      changes also did not persist during the SR morphine period. Intensity of pain was
      associated with a lower level of function and higher intensity of symptoms, but
      only with relatively small (not higher than 0.44) correlation coefficients.
      Compared to normative data from the general population, physical function, role
      function, social function, and global health were impaired in the study patients.
      The patients also suffered more fatigue, pain, nausea/vomiting, appetite loss,
      and constipation. In conclusion, in cancer patients with reduced HRQL, the start
      of morphine therapy had no major influence on aspects of HRQL other than pain.

PMID- 10946166
TI  - Opioid responsiveness-primary diagnosis relationship in advanced cancer patients
      followed at home.
AB  - The aim of this study was to evaluate the influence of the primary cancer on pain
      characteristics and opioid response, in terms of analgesia and adverse effects,
      in advanced cancer patients followed at home. A prospective study was carried out
      in a sample of 434 consecutive advanced cancer patients who required opioids
      during the last four weeks of life. One hundred eighty-one patients received
      opioids for longer than the four weeks and were considered for this analysis.
      Demographic data, primary diagnosis, and pain mechanisms were recorded, and mean
      opioid doses, pain intensity, and symptoms were assessed at weekly intervals
      during the last four weeks of life. In the group of 181 patients, somatic pain
      was associated with lung, head and neck, breast, and prostate cancer (p <
      0.0005), while visceral pain was associated with colorectal, gastric, liver,
      pancreatic, and uterine cancer (p < 0.0005). Considering all primary diagnoses,
      there was a significant increase in the mean opioid dose (p < 0.0005) across the
      four weekly periods. There was a significant decrease in pain intensity scores (p
      < 0.0005) in all cases. A significant dose increase was observed only for
      mesothelioma (p = 0. 027) when compared with other types of cancer. In all 181
      cases, a significant worsening in symptom intensity was observed during the last
      two weeks of life (p < 0.01). This study shows that primary cancer may have an
      influence on pain characteristics and opioid response. Patients with some kinds
      of cancer may be at risk of developing severe pain syndromes or more adverse
      effects.

PMID- 10946167
TI  - Building an institutional commitment to pain management in long-term care
      facilities.
AB  - This report reviews the development, implementation and findings of an inter
      institutional study directed to the goal of making pain management an
      institutional priority in Wisconsin long-term care facilities. A total of 87
      facilities were recruited in two training cohorts. Each facility identified a
      team of individuals, with responsibility and authority for care policies within
      their institution, to participate in four structured educational programs. Each
      team completed an Action Plan, structured around 14 national practice indicators
      of an institutional commitment to pain management. At baseline, 14% of facilities
      had > 51% of the indicators in place; at conclusion 74% of facilities had > 51%
      of indicators in place. This education project was successful across training
      cohorts at implementing critical pain management target indicators.

PMID- 10946168
TI  - Management of spasticity associated pain with botulinum toxin A.
AB  - Lesions of the central nervous system often result in an upper motor neuron
      syndrome including spasticity, paresis with pyramidal signs, and painful spasms.
      Pharmacological treatment with oral antispasticity drugs is frequently associated
      with systemic side effects which limit their clinical use. Botulinum Toxin A
      (BtxA) injected in spastic muscles has been shown to be effective in reducing
      muscle tone, but only few studies have reported pain relief as additional
      benefit. Therefore, we investigated the effects of local BtxA injections in 60
      patients with acute (< 12 months) and chronic spasticity and pain in a
      prospective multicenter study. Target muscles for BtxA were selected on the basis
      of clinical examination. Intramuscular BtxA injections were placed in muscles
      exhibiting increased muscle tone in combination with pain during passive joint
      movement. Patients received a mean total dose of 165.7 +/- 108.2 [30-400] units
      BOTOX((R)) per treatment session in a mean 3.4 +/- 1.5 muscles. Baseline and
      follow-up (mean 5.9 weeks) measures included a patient self-assessment of pain
      and function on a five-level scale, a physician's evaluation of function, and a
      global rating of response to BtxA. Fifty-four of sixty patients experienced
      improvement in pain without subjective functional improvement. The effects were
      comparable in acute (n = 17) and chronic (n = 43) spasticity. Physician's
      assessment of gain in function increased significantly (p < 0.05) only in
      patients with chronic spasticity. No serious adverse event was observed. Mild
      reversible side effects (local pain, hematoma, edema, mild weakness) were
      observed in four patients. In conclusion, we found that intramuscular BtxA
      injections are a potent, well-tolerated treatment modality to significantly
      reduce spasticity-related local pain. This problem may be a main indication,
      especially in patients with poor response or intolerable side effects to oral
      medication.

PMID- 10946169
TI  - Allodynia and pinprick hypesthesia in acute herpes zoster, and the development of
      postherpetic neuralgia.
AB  - Sensory loss and allodynia are hallmark signs of postherpetic neuralgia (PHN). We
      set out to investigate how frequently these signs are present in patients with
      acute herpes zoster (HZ) and what their prognostic value might be. We assessed
      pain, mechanical allodynia, and sensitivity to pinprick in 113 immunocompetent
      patients with HZ of a median duration of 5 days. Follow-up visits took place at 2
      weeks, 6 weeks, 3 months, and 6 months. When first seen, 87 (77%) patients
      reported ongoing pain and 48/107 (45%) had allodynia. Twenty-eight (25%) patients
      had pain at 3 months (and were considered to have developed PHN), while 14 (12%)
      patients had pain at 6 months. Allodynia tended to subside quickly in most
      patients. Reduced sensitivity to pinprick was less common. Mechanical allodynia
      and pinprick hypesthesia were strongly associated with the development of PHN.
      They merit addition to the list of potential risk factors for PHN although they
      cannot be used as a predictive rule for an individual patient. By contrast, lack
      of allodynia in the early stages of HZ predicts good recovery by three months.

PMID- 10946170
TI  - Variability of analgesic practices for hospitalized children on different
      pediatric specialty units.
AB  - This study examined the differences in the prescription and administration of
      analgesics in eight pediatric specialty units. Medical records of patients (n =
      153) who were reported by nurses to be having pain were reviewed. Results showed
      that there were variations in the type of analgesics prescribed and administered
      in the different units. Mean doses of opioids were slightly subtherapeutic. The
      mean doses of the nonsteroidal anti-inflammatory drugs and adjuvants were all
      within the therapeutic range. There were large intervals between doses of
      medications. Because few patients had pain scores recorded before and after
      analgesic administration, evidence of relief was inconclusive, and the actual
      effectiveness of analgesics could not be consistently evaluated. Undertreatment
      of pain may result from administration of subtherapeutic analgesic doses, long
      intervals between administrations of doses, lack of proper documentation to guide
      practice, or a combination of these reasons.

PMID- 10946171
TI  - Health-related quality of life in chronic refractory reflex sympathetic dystrophy
      (complex regional pain syndrome type I).
AB  - The aim of this study was to find out which aspects of health-related quality of
      life (HRQL), measured with generic instruments, are important to patients with
      reflex sympathetic dystrophy (RSD) affecting the arm or leg. The Sickness Impact
      Profile 68 (SIP68), the Nottingham Health Profile (NHP), and the EuroQol-5D (EQ
      5D) were completed by 54 patients suffering from RSD (33 arm, 21 leg). The scores
      of the three questionnaires for patients with an affected arm or leg are
      presented. Aspects relevant to patients with RSD of the arm include the NHP1
      dimensions of pain (mean score: 63%), sleep (58%), and energy (45%), and the EQ
      5D dimensions of pain (67% extreme), usual activities (76% some problems), and
      self care (76% some problems). Aspects relevant to patients with RSD of the leg
      include the SIP68 dimensions of social behavior (51%) and mobility control (46%),
      the NHP 1 dimensions of pain (mean score: 86%), mobility (54%), energy (53%), and
      sleep (52%), and the EQ-5D dimensions of mobility (81% some problems), pain (71%
      extreme), and usual activities (71% some problems). The study showed that
      applying generic HRQL instruments and measuring treatment effect with the
      dimensions scoring high provides a responsive instrument which at the same time
      gains information concerning dimensions not maximally responsive to a specific
      disease. Some dimensions which, on the basis of their label, might be expected to
      be important were found not to be so. After using this approach, clinicians can
      more directly focus treatment on specific areas that have been shown to affect a
      patient's HRQL.

PMID- 10946172
TI  - Recent onset of abdominal pain in a patient with advanced breast cancer.
AB  - Abdominal pain is a frequent complaint heard in medical practice. For palliative
      care patients, there are numerous causes of abdominal pain. Because of the non
      invasive nature of palliative care practice, emphasis is made on minimal
      investigations. We present a case of a 49-year old patient who developed
      progressive abdominal pain and was found to have gangrenous appendicitis. The
      patient underwent surgery and was able to be discharged home. Our findings
      suggest that any new pain in a cancer patient must be carefully evaluated.
      Because of the presence of opioid analgesics and corticosteroids, symptoms can be
      less severe and related to diagnosis in palliative care patients.

PMID- 10946173
TI  - The lens and angle-closure glaucoma.

PMID- 10946174
TI  - Consultation section: cataract surgical problem.

PMID- 10946175
TI  - Consultation section

PMID- 10946176
TI  - Consultation section

PMID- 10946177
TI  - Consultation section

PMID- 10946179
TI  - Consultation section

PMID- 10946178
TI  - Consultation section

PMID- 10946180
TI  - Consultation section

PMID- 10946181
TI  - Consultation section

PMID- 10946182
TI  - Consultation section

PMID- 10946183
TI  - Consultation section

PMID- 10946184
TI  - Removing silicone oil droplets from the posterior surface of silicone intraocular
      lenses.
AB  - A 67-year-old woman had droplets of silicone oil adhering to her silicone
      intraocular lens (IOL) resulting from a previous silicone oil tamponade. A lens
      hook and intraocular irrigation were used in conjunction by inserting an infusion
      cannula to remove the droplets. This restored clarity of the visual axis,
      improved visual acuity, and eliminated the need for IOL replacement. The
      technique is simple and less invasive than IOL exchange and may become the
      preferred way to remove silicone droplets from an IOL.

PMID- 10946185
TI  - Correction of high astigmatism with astigmatic keratotomy combined with laser in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the efficacy, predictability, and stability of a combined
      procedure, arcuate keratotomy and laser in situ keratomileusis (LASIK), for the
      correction of high astigmatism. SETTING: Instituto de Microcirugia Ocular (IMO),
      Barcelona, Spain. METHODS: Fifteen eyes of 11 patients with naturally occurring
      astigmatism (NOA) (86. 66%) or surgically induced astigmatism (SIA) (13.34%)
      between -3.00 and -8.00 diopters (D) who had astigmatic keratotomy were studied.
      The patients had a secondary procedure, LASIK, to correct the residual refractive
      error. RESULTS: Mean baseline spherical equivalent refraction was -2.47 D +/-
      3.69 (SD) and mean refractive cylinder, -4.59 +/- 1.66 D. Twelve months after
      LASIK, mean spherical equivalent was -0.09 +/- 1.50 D and the mean refractive
      cylinder, -1. 21 +/- 1.07 D. The mean cylindrical correction attempted in the NOA
      group was -4.05 +/- 1.19 D and in the SIA group, -7.00 +/- 1.41 D.
      Postoperatively, the values were -1.50 +/- 1.17 D and -1.62 +/- 0.17 D,
      respectively. Twelve months after LASIK, the uncorrected visual acuity (UCVA) was
      0.5 +/- 0.1. The UCVA in the NOA group (0.50 +/- 0. 08) was better than in the
      SIA group (0.32 +/- 0.10). The efficacy index was 0.96 overall. Best corrected
      visual acuity deteriorated by 1 Snellen line in 1 case (6.6%) but improved by 1
      and 2 Snellen lines in 4 cases (26.6%) and 2 cases (13.3%), respectively. All
      procedures were completed without adverse reactions intraoperatively or
      postoperatively. CONCLUSION: This combined technique was effective in the
      treatment of high astigmatism, with excellent results compared with the results
      of each procedure alone. Because of its high predictability, we strongly
      recommend the technique in cases with astigmatism higher than 3.0 D, particularly
      in those with astigmatism higher than 5.0 D.

PMID- 10946186
TI  - Iatrogenic keratectasia after laser in situ keratomileusis for less than -4.0 to 
      7.0 diopters of myopia.
AB  - PURPOSE: To study 13 eyes with less than -4.0 to -7.0 diopters of myopia that
      developed central or inferior keratectasia after laser in situ keratomileusis
      (LASIK). METHODS: The progress of the ectasia was determined by a series of pre-
      and post-LASIK topographies and the case histories. RESULTS: Progressive ectasia
      developed from 1 week to 27 months after LASIK. This necessitated the wearing of
      hard contact lenses or penetrating keratoplasty. One eye improved for some months
      after photorefractive keratectomy retreatment. Two eyes in 1 patient and 1 eye in
      a second patient had latent keratoconus before surgery. CONCLUSION: Laser in situ
      keratomileusis can cause permanent weakening and ectasia of the cornea even in
      eyes with low myopia.

PMID- 10946187
TI  - Effect of intrastromal corneal ring segment shift on clinical outcome: one year
      results for low myopia.
AB  - PURPOSE: To evaluate the effect of intrastromal corneal ring segment (ICRS) shift
      on clinical outcome. SETTING: Chu Morvan Ophthalmology Service, Brest, France.
      METHODS: Forty-seven eyes with myopia from -1.0 to -5.0 diopters (D) had ICRS
      surgery according to United States Food and Drug Administration protocol using a
      2-segment implant design. Visual acuity, refractive, videotopographic, and
      biomicroscopic results in eyes that did not have contact between segments (Group
      A, n = 26) and in eyes that did have contact (Group B, n = 21) were compared.
      RESULTS: Soon after surgery, migration of and subsequent contact between the
      implant segments occurred in 21 eyes (45%). Contact between the inferior ends was
      most common, occurring in 19 eyes; in the remaining 2 eyes, the superior ends of
      the implant touched. Superior contact was associated with superficial channels,
      wound-healing problems, and ICRS explantation. No segment shift was observed
      after the first postoperative week. No significant differences in visual acuity,
      qualitative vision, or density of intrastromal deposits were noted between the 2
      groups. However, at 6 months there was more induced with-the-rule cylinder in
      Group B (mean +1.3 D +/- 0.7 [SD]) than in Group A (mean +0.7 +/- 0.5 D).
      Astigmatism was clinically significant in only 3 cases at 3 months. CONCLUSIONS:
      Induced cylinder remains a limitation of the ICRS procedure, and segment contact
      appears to influence the rate of induced cylinder. Overall, however, the ICRS
      procedure produces promising results. Research efforts are underway to address
      induced cylinder and channel deposits associated with ICRS surgery.

PMID- 10946188
TI  - Penetrating keratoplasty for keratoconus: a long-term review of results and
      complications.
AB  - PURPOSE: To study the long-term complications of penetrating keratoplasty (PKP)
      to evaluate current recommendations to patients with keratoconus. SETTING: John
      Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS:
      Retrospective study of all PKP procedures for keratoconus performed by 4 surgeons
      during a 312 year period. Follow-up was 1 day and 1, 3, 6, 12, and 24 months post
      PKP. Data from 93 eyes were reviewed for allograft reaction, astigmatism, visual
      acuity, reasons for decreased visual acuity, and other complications. RESULTS:
      Allograft reaction was seen in 31% of cases but no graft failure due to allograft
      reaction. Mean astigmatism was 2.76 diopters (D) +/- 1.99 (SD) at 24 months, with
      only 15% > 5.00 D. Last best corrected visual acuity was 20/25 or better in 77%
      of cases (87% had 20/25 or better at some time during follow-up). Complications
      that did not cause decreased visual acuity were noted. Punctate keratitis was
      noted in 20% of patients 180 days or more after surgery. CONCLUSIONS: Penetrating
      keratoplasty is a good treatment option for patients with keratoconus but should
      be reserved for those who do not tolerate contact lenses or do not get needed
      visual acuity with contact lenses because of complications. This procedure has
      become a second-line treatment for keratoconus patients and has generally good
      results.

PMID- 10946189
TI  - Effect of lamellar flap location on corneal topography after laser in situ
      keratomileusis.
AB  - PURPOSE: To investigate the effect of hinge position on corneal topography after
      laser in situ keratomileusis (LASIK) for myopia. SETTING: Academic center and
      refractive surgery practice. METHODS: Topography data obtained from 89 eyes of 46
      patients after LASIK were analyzed. Using a system of Cartesian coordinates, data
      along the horizontal and vertical axes were analyzed, measuring sagittal height
      and power change at 1 mm intervals from the ablation zone center. Data points
      that were equidistant and on opposite sides of the ablation center were compared
      to find asymmetry along either axis relative to nasally hinged flaps. RESULTS:
      Along the horizontal axis, areas of the cornea closer to the hinge had a higher
      topography than areas farther from the hinge. Specifically, the points nearest
      and farthest from the hinge were significantly different in sagittal height (P
      <.034); the areas farthest from the hinge were reduced more after surgery
      (relatively lower topography). When results were stratified into low- and high
      diopter corrections, this difference was significant in only the high-diopter
      group (P <.0006). Trends in power change were also observed. Areas of the cornea
      closer to the hinge were relatively flatter than areas farther from the hinge.
      Statistical significance was detected in only the low-diopter group at data
      points 2 mm from the ablation zone center in opposite directions (P <.008). No
      asymmetry was seen along the vertical axis in power change or sagittal height.
      CONCLUSIONS: The lamellar flap in LASIK may influence postoperative corneal
      topography. Hypothetically, the corneal flap may retract toward the hinge,
      producing axial asymmetry in the postoperative topography relative to the hinge.
      Understanding the influence of corneal flap characteristics on post-LASIK
      topography may improve optical results and may be particularly important in the
      development and effectiveness of topography-guided ablation techniques.

PMID- 10946190
TI  - Initial experience with a refractive multifocal intraocular lens in a Japanese
      population.
AB  - PURPOSE: To evaluate a poly(methyl methacrylate) refractive, zonal-progressive
      multifocal intraocular lens (IOL) in patients requiring cataract surgery.
      SETTING: Department of Ophthalmology, Saiseikai Kurihashi Hospital, Saitama,
      Japan. METHODS: This open-label noncomparative study evaluated 58 eyes of 31
      Japanese patients who had cataract surgery and implantation of a multifocal IOL
      (Array(R) PA154N, Allergan Surgical). The main outcome measures were visual
      acuity (VA) (distance and near, with and without correction), glare disability,
      and contrast sensitivity (CS) (distance and near, with and without glare under
      day and night conditions). A questionnaire was used to evaluate the effectiveness
      of the multifocal IOL. RESULTS: Uncorrected distance VA was 0.7 or better (20/30)
      in 56 eyes (97.0%) and uncorrected near VA, 0.5 or better (20/40) in 52 eyes
      (89.7%). Corrected distance VA was 0.7 or better in all eyes. Near VA with
      distance correction was 0.5 or better in 51 eyes (87.9%). Daytime CS was within
      the normal range. However, nighttime CS with central glare for both distance and
      near was markedly decreased. Under all conditions, distance CS was significantly
      better than near CS from middle- to high-frequency areas. Seventy-four percent of
      patients with the IOL in both eyes did not need glasses for daily activities, and
      the others needed glasses only to read for long periods. CONCLUSIONS: The results
      indicate that this refractive multifocal IOL is distance dominant and is
      beneficial in Japanese patients. However, since there are differences between
      Western countries and Japan in distance reading of characters and letters,
      further modification of this multifocal IOL may be required for use in Japanese
      patients.

PMID- 10946191
TI  - Bilateral cataract surgery in adult and pediatric patients in a single session.
AB  - PURPOSE: To evaluate the results of bilateral simultaneous cataract surgery in
      adult and pediatric patients under local or general anesthesia. SETTING:
      Department of Ophthalmology, Inonu University, Turgut Ozal Medical Center,
      Malatya,Turkey. METHODS: Eighty-two eyes of 41 patients were included in the
      study. Twelve of 17 pediatric patients with congenital cataract had bilateral
      simultaneous lensectomy, posterior capsulotomy, and anterior vitrectomy; 5
      patients, aged 10 to 19 years, had bilateral extracapsular cataract extraction
      (ECCE) with posterior chamber intraocular lens (PC IOL) implantation. Forty-eight
      eyes of 24 adult patients had bilateral simultaneous ECCE with primary (43 eyes)
      or secondary (5 eyes) PC IOL implantation. Local anesthesia was administered to
      20 adult patients by retrobulbar injection; the other cases were performed using
      general anesthesia. The procedures were treated as 2 separate surgeries in the
      same session; care was taken to ensure surgical asepsis. RESULTS: No serious
      intraoperative complications occurred such as posterior capsule rupture, vitreous
      loss, endophthalmitis, and anesthesia-related problems. Of patients tested, 84.4%
      achieved a final best corrected visual acuity of 6/12 or better and 31.0%, of 6/6
      or better. CONCLUSIONS: Simultaneous bilateral cataract surgery was not
      associated with an increased rate of complications, and visual results were good.
      If strict rules of surgical asepsis are followed, this may be a useful option in
      a variety of bilateral cases using general or local anesthesia.

PMID- 10946192
TI  - Primary phacoemulsification for uncontrolled angle-closure glaucoma.
AB  - PURPOSE: To report the results of primary phacoemulsification to treat
      uncontrolled angle-closure glaucoma. SETTING: Private practice and teaching
      hospital department. METHODS: This retrospective interventional case series
      assessed 3 patients having phacoemulsification and posterior chamber intraocular
      lens implantation for uncontrolled intraocular pressure (IOP) after acute primary
      angle-closure glaucoma. RESULTS: Intraocular pressure control was achieved in all
      patients postoperatively. CONCLUSIONS: Primary phacoemulsification with the
      option of future trabeculectomy should be considered in selected patients with
      persistent appositional angle closure and uncontrolled IOP after angle-closure
      glaucoma.

PMID- 10946193
TI  - Update on a long-term, prospective study of capsulotomy and retinal detachment
      rates after cataract surgery.
AB  - PURPOSE: To evaluate the retinal detachment risks and neodymium:YAG (Nd:YAG)
      capsulotomy rates associated with different cataract approaches and intraocular
      lens (IOL) styles in a long-term,prospective clinical study. SETTING: Clinical
      practice of 1 ophthalmologist, Fort Collins, Colorado, USA. METHODS:
      Prospectively studied were surgical approach, date, and complications; IOL type;
      axial length; patient age and sex; Nd:YAG capsulotomy and date; and retinal
      detachment and date. RESULTS: Phacoemulsification had a lower risk of retinal
      detachment than intracapsular cataract extraction (ICCE) (0.4% versus 5.4%; P
      <.001) and extracapsular cataract extraction (ECCE) (0.4% versus 1.6%; P =. 002).
      Although retinal detachment was significantly associated with Nd:YAG for ECCE
      (3.1% versus 1.0%; P =.01), no patient in the phacoemulsification group had a
      retinal detachment after an Nd:YAG treatment. Retinal detachment was strongly
      associated with axial length of 24.0 mm and greater (P <.001), age of 60 years or
      less if axial length was 24.0 mm or greater (for ECCE, P =.001; for
      phacoemulsification, P =.01) and sex; that is, male (for ECCE, P =. 04; for
      phacoemulsification, P =.02). Regarding IOL styles the Surgidev B20/20 (P <.001)
      and AcrySof MA60 (P <.001) had significantly lower Nd:YAG rates, while the Cilco
      UPB 320 GS had a significantly higher Nd:YAG rate (P <.001). CONCLUSIONS:
      Cataract surgical approach and IOL style significantly affect Nd:YAG and retinal
      detachment rates. Being a man, being 60 years or younger, and especially having
      an axial length of 24.0 mm or greater were associated with detachment. Some
      Nd:YAG approaches may not put the patient at increased risk for retinal
      detachment.

PMID- 10946194
TI  - Astigmatism correction with a foldable toric intraocular lens in cataract
      patients.
AB  - PURPOSE: To determine the efficacy and rotational stability of a toric posterior
      chamber silicone intraocular lens (IOL) to correct preoperative astigmatism in
      cataract patients. SETTING: Department of Ophthalmology, University Hospital of
      Vienna, Vienna Austria. METHODS: Between 1993 and 1998, foldable toric single
      piece plate-haptic silicone IOLs were implanted in 37 eyes (30 patients). The
      cylindrical IOL power was 2.00 diopters (D) (n = 29), 3.50 D (n = 7), or 4.00 D
      (n = 1). Phacoemulsification was performed through a scleral or a corneal
      sutureless self-sealing incision. Outcomes of Snellen visual acuity (without,
      with spherical, and with best correction), refractive and keratometric
      astigmatism, and IOL rotation after early postoperative (mean 15.9 days +/- 10.1
      [SD]) and long-term (mean 20.3 +/- 16.6 months) follow-ups were evaluated.
      RESULTS: At last follow-up, 31 eyes (83.8%) had a spherically corrected and 34
      (91.9%) a best corrected visual acuity of 0.5 (20/40) or better. Mean
      preoperative refractive and keratometric astigmatism was 2.68 and 2.70 D,
      respectively. At the last postoperative follow-up, mean refractive astigmatism
      was reduced to 0.84 D; keratometric astigmatism was 2.30 D. In 7 eyes (18.9%),
      the IOL axis was rotated a maximum of 25 degrees. In all 37 eyes, the axis of the
      toric IOL remained within 30 degrees of rotation. CONCLUSIONS: Early
      postoperative and long-term follow-ups showed effective and stable correction of
      astigmatism after implantation of a foldable toric posterior chamber silicone
      IOL.

PMID- 10946195
TI  - Iris fixation of posterior chamber intraocular lenses.
AB  - PURPOSE: To describe a technique for suture fixation of silicone intraocular
      lenses (IOLs) to the iris and compare the outcomes to those in published data.
      SETTING: Subspecialty cornea/anterior segment private practice, Indianapolis,
      Indiana, USA. METHODS: This retrospective review comprised 121 consecutive cases
      of secondary IOL implantation or IOL exchange between 1993 and 1998. All cases
      had concurrent anterior or posterior vitrectomy. Intraocular lens exchange was
      performed in 96 eyes, secondary IOL implantation in 20 eyes, and primary IOL
      implantation in 5 eyes. Penetrating keratoplasty (PKP) was performed concurrently
      in 93 eyes, extracapsular cataract extraction in 1 eye, intracapsular cataract
      extraction in 2 eyes, pars plana lensectomy in 2 eyes, and Molteno tube shunt
      placement for uncontrolled glaucoma in 1 eye. Outcomes measured were graft
      survival, visual acuity, new onset or worsening of glaucoma, and complications
      related to surgery. RESULTS: Graft survival at last follow-up was 89.2% in
      patients having PKP. Visual acuity was 20/80 or better in 58.3% and 20/40 or
      better in 30.5% of eyes with transplants. Without transplants, visual acuity was
      20/80 or better in 82.0% and 20/40 or better in 57.1%. Glaucoma developed or
      worsened in 24.7% and improved in 16.1% with transplants; it developed or
      worsened in 7.0% and improved in 17.8% without transplants. Retinal detachment
      occurred in 1 eye with a transplant. In the nontransplant group, major
      complications were bullous keratopathy (n = 2) and tilted IOL (n = 1).
      CONCLUSIONS: Iris fixation of posterior chamber silicone IOLs may decrease the
      possibility of late suture breakage and dislocation of the IOL, as well as the
      risk of endophthalmitis. Graft survival, visual acuity, glaucoma, and
      complications are similar to those of other methods of IOL fixation reported in
      the literature.

PMID- 10946196
TI  - Phacoemulsification and intraocular lens placement in eyes with cataract and
      congenital coloboma: visual acuity and complications.
AB  - PURPOSE: To evaluate the safety and complications of phacoemulsification in a
      series of patients with congenital coloboma and cataract. SETTING: University
      based hospital practice. METHODS: A retrospective review was conducted of
      consecutive patients who had coloboma and cataract and had phacoemulsification
      between January 1987 through December 1998. Complications and visual acuity 2
      months postoperatively were assessed. RESULTS: Mean age of 7 cases at the time of
      surgery was 41.6 years +/- 11.1 (SD). Visual acuity improved in 6 of 7 eyes; 1
      eye had no change. Six eyes had no serious complications. In 1 eye, a retinal
      detachment was observed postoperatively, but there was no loss in visual acuity.
      Another patient developed postoperative monocular diplopia from exposure of the
      intraocular lens (IOL) edge within the inferonasally located corectopia
      associated with the coloboma. Nonsurgical treatment was unsuccessful, but this
      symptom resolved after surgical pupilloplasty. CONCLUSIONS: The results of this
      small case series affirm that clinically significant cataract develops at a
      younger age in eyes with congenital coloboma than in eyes with typical age
      related nuclear sclerotic cataract. Monocular diplopia, a potential complication
      after cataract surgery in these eyes, can be managed by pupilloplasty. The
      improved vision in this study indicates that phacoemulsification and IOL
      placement are safe and beneficial in patients with typical congenital coloboma
      and cataract.

PMID- 10946197
TI  - Phacoemulsification in eyes with white cataract.
AB  - PURPOSE: To study the results of phacoemulsification in eyes with white cataract.
      SETTING: Aravind Eye Hospital, Madurai, India. METHODS: This retrospective study
      comprised 212 consecutive patients with white cataract: 192 mature (90.6%), 11
      intumescent (5.2%), and 9 hypermature (4.2%). Patients had phacoemulsification
      and continuous curvilinear capsulorhexis. After the nucleus was removed by the
      divide and conquer or the phaco chop technique, a posterior chamber intraocular
      lens was implanted. Preoperative and intraoperative findings, as well as
      postoperative outcomes, were analyzed. RESULTS: Intraoperative complications
      included premature entry of the tunnel into the anterior chamber in 4 eyes
      (1.9%), incomplete capsulorhexis in 60 (28.3%), posterior capsular tear in 4
      (1.9%), conversion to a manual nonphacoemulsification technique in 4 (1.9%),
      intraoperative miosis in 7 (3.3%), and iris chafing in 2 (0.9%). Mean
      phacoemulsification time was 2.03 minutes (range 0 to 5.8 minutes). A best
      corrected visual acuity of 6/9 or better was attained in 131 patients (61.8%) on
      the first postoperative day and in 199 patients (93.9%) at 1 month. Postoperative
      complications included moderate transient striate keratopathy with corneal edema
      in 12 eyes (5.7%) and iritis in 2 (0.9%). CONCLUSIONS: Phacoemulsification was a
      safe and effective technique to remove white mature cataract in eyes in a
      developing country.

PMID- 10946198
TI  - Small incision extracapsular cataract surgery with manual phacotrisection.
AB  - PURPOSE: To evaluate the safety and efficacy of small incision extracapsular
      cataract extraction (ECCE) using the manual phacotrisection technique. SETTING:
      Department of Ophthalmology, Turgut Ozal Medical Center, InonuUniversity,
      Malatya, Turkey. METHODS: Fifty-nine eyes of 54 patients had small incision ECCE
      by the manual phacotrisection technique. Mean follow-up was 10 months. After
      capsulorhexis and hydrodissection were performed, the endonucleus was prolapsed
      into the anterior chamber and trisected using an anteriorly positioned triangular
      trisector and posteriorly placed solid vectis. Pieces were extracted with a
      forceps through a small incision. RESULTS: Postoperatively, best spectacle
      corrected visual acuity of 20/40 or better was achieved in 48 eyes (83%) and of
      20/25 or better in 28 eyes (47%). The most frequent intraoperative complication
      was posterior capsule rupture (n = 5). Of eyes that developed posterior capsule
      rupture, 3 had vitreous loss and 2 had implantation of an anterior chamber
      intraocular lens (IOL). In 44 eyes, the IOL was implanted in the bag and in 12
      eyes, in the ciliary sulcus. The most significant postoperative complication was
      transient corneal edema, which developed in 32 eyes (54%). No permanent
      complications (e.g., corneal endothelial decompensation) occurred in any case.
      CONCLUSIONS: Manual phacotrisection has several advantages such as nucleus
      safety, less dependence on assistant personnel, the elimination of the phaco
      machine, and cost effectiveness.

PMID- 10946199
TI  - Dye-enhanced cataract surgery. Part 1: anterior capsule staining for
      capsulorhexis in advanced/white cataract.
AB  - PURPOSE: To evaluate anterior capsule staining using 3 dyes to perform continuous
      curvilinear capsulorhexis (CCC) in postmortem human eyes with advanced/white
      cataract. SETTING: Center for Research on Ocular Therapeutics and Biodevices,
      Storm Eye Institute, Medical University of South Carolina, Charleston, South
      Carolina, USA. METHODS: In experimental closed-system surgery, CCC was performed
      in 12 postmortem human eyes with cataract after the anterior capsule was stained
      with 3 capsule dyes (fluorescein sodium 2%, indocyanine green [ICG] 0.5%, and
      trypan blue 0.1%). Two commonly used techniques for capsule staining were also
      compared: staining within an air bubble and intracameral subcapsular injection of
      dye. RESULTS: In all globes, CCC was uneventful using the 3 dyes and with both
      techniques. With the intracameral subcapsular injection, the dye remained trapped
      in the subcapsular space in contact with the posterior surface of the anterior
      capsule, allowing enough time to perform any maneuver. The staining provided by
      ICG, at the concentration used, was slightly superior to that of the other dyes.
      Leakage of fluorescein sodium into the vitreous cavity was seen using the Miyake
      Apple posterior video/photographic technique. CONCLUSION: Intracameral
      subcapsular injection of ICG allowed the easiest recognition of the capsular flap
      by staining the posterior surface of the anterior capsule and without leaking
      into the vitreous cavity.

PMID- 10946200
TI  - Dye-enhanced cataract surgery. Part 2: learning critical steps of
      phacoemulsification.
AB  - PURPOSE: To use capsule dyes to enhance visualization to learn and perform
      various critical steps of the phacoemulsification procedure in a laboratory
      setting using postmortem human eyes. SETTING: Center for Research on Ocular
      Therapeutics and Biodevices, Storm Eye Institute, Medical University of South
      Carolina, Charleston, South Carolina, USA. METHODS: Indocyanine green 0.5% (ICG)
      and trypan blue 0.1% were used to enhance visualization for performing critical
      steps of phacoemulsification in 8 human eyes obtained postmortem. All eyes were
      prepared according to the Miyake-Apple posterior video technique. After a
      continuous curvilinear capsulorhexis (CCC) was made, the dyes were used to
      enhance visualization for hydrodissection, hydrodelineation, and various
      maneuvers for nuclear emulsification and cortical cleanup. In 8 eyes, all the
      aforementioned steps were performed without using dye (control group). RESULTS:
      Both dyes helped enhance visualization during the critical steps of
      phacoemulsification. The use of a dye solution instead of balanced salt solution
      (BSS) for hydrodissection/delineation helped localize the complete plane of
      cleavage between the capsule and cortex and the nucleus-epinucleus complex.
      During various nuclear sculpting maneuvers, the use of dye helped visualization
      of the position of the phaco tip and its relation to the posterior capsule. It
      also helped localize remaining cortical fibers, facilitating complete cleaning of
      the capsular bag. CONCLUSIONS: Dye-enhanced cataract surgery was useful in
      learning various critical steps of phacoemulsification in a wet laboratory
      setting.

PMID- 10946201
TI  - Dye-enhanced cataract surgery. Part 3: posterior capsule staining to learn
      posterior continuous curvilinear capsulorhexis.
AB  - PURPOSE: To evaluate the use of 2 dyes for staining the posterior capsule to
      enhance visualization during posterior continuous curvilinear capsulorhexis
      (PCCC). SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm
      Eye Institute, Medical University of South Carolina, Charleston, South Carolina,
      USA. METHODS: Indocyanine green 0.5% (ICG) and trypan blue 0.1% were used to
      stain the posterior capsule for performing PCCC in 8 human eyes obtained
      postmortem. The eyes were prepared according to the posterior video technique of
      Miyake-Apple. After CCC and hydrodissection/delineation were performed, the
      nucleus was carefully delivered by hydroexpression. Cortical cleanup was
      completed by irrigation/aspiration. The posterior capsule was stained by
      instilling 1 microdrop of ICG (4 eyes) or trypan blue (4 eyes) in the capsular
      bag. A PCCC was then performed by 2 independent surgeons (4 eyes/surgeon) not
      familiar with this technique. Each surgeon also performed PCCC in 2 eyes without
      the use of dye. RESULTS: Both dyes facilitated the performance of PCCC after
      staining the otherwise transparent posterior capsule. It was easier to
      differentiate the stained posterior capsule flap from the underlying transparent
      anterior hyaloid phase of the vitreous. In addition, optic capture of an
      intraocular lens, with or without anterior vitrectomy, was easily accomplished
      because of the enhanced visualization by posterior capsule staining. CONCLUSIONS:
      Posterior capsule staining can be successfully used to learn and perform the PCCC
      procedure, combined with optic capture, anterior vitrectomy, or both.

PMID- 10946202
TI  - Diffuse lamellar keratitis: diagnosis and management.
AB  - With the volume of laser in situ keratomileusis procedures growing exponentially,
      ophthalmologists and other eye-care providers are becoming aware of an uncommon
      postoperative condition, diffuse lamellar keratitis, that can affect an otherwise
      ideal outcome. We present our strategy for diagnosing and managing this syndrome,
      developed from experience in a high-volume refractive surgical practice.
      Understanding the time course of the disease, along with proper identification,
      staging, and intervention, can help eliminate visual loss associated with this
      condition.

PMID- 10946203
TI  - Keratopathy and pachymetric changes after photorefractive keratectomy and
      vitrectomy with silicone oil injection.
AB  - We present a man who, after bilateral excimer laser photorefractive keratectomy
      (PRK) for high myopia in the right eye, had repeated retinal detachment surgery
      with lensectomy and injection of silicone oil. Visual acuity fluctuated in
      accordance with significant central corneal thickness diurnal variation. The case
      illustrates the possibility of PRK as a predisposing factor for keratopathy after
      retinal detachment surgery with silicone injection in an aphakic eye.

PMID- 10946204
TI  - Capsular block syndrome and pseudoexpulsive hemorrhage.
AB  - Capsular block syndrome (CBS) has been recognized as a cause of immediate or
      delayed postoperative accumulation of fluid behind an intraocular
      lens/capsulorhexis complex. Hydrodissection-related rupture of the posterior
      capsule may be considered a variant of CBS that can manifest intraoperatively. We
      describe another intraoperative situation related to CBS in which fluid
      loculation during hydrodissection mimics a threatened expulsive hemorrhage.

PMID- 10946205
TI  - Propionibacterium acnes endophthalmitis requiring intraocular lens removal after
      failure of medical therapy.
AB  - A 52-year-old Saudi man developed intraocular inflammation 7 weeks after
      uneventful phacoemulsification with implantation of a silicone posterior chamber
      intraocular lens (IOL). Cultures from the aqueous and vitreous were repeatedly
      negative, but a temporary response to intracameral and intravitreal injection of
      vancomycin was noted. A series of 6 intraocular injections given over 5 days
      failed to resolve the inflammation. It did, however, disappear after the IOL was
      removed. The IOL provided the only positive culture in this case of
      Propionibacterium acnes endophthalmitis. Nine months later, a posterior chamber
      poly(methyl methacrylate) IOL was implanted. Eighteen months later, the patient
      had no recurrences. He regained a visual acuity of 20/30, corresponding to his
      best postoperative result.

PMID- 10946206
TI  - Combined cataract extraction and submacular blood clot evacuation for globe
      perforation caused by retrobulbar injection.
AB  - A 45-year-old woman, originally scheduled for cataract surgery in the left eye,
      was referred for management of a globe perforation noticed after the retrobulbar
      injection of an anesthetic solution. There was a moderate degree of vitreous
      hemorrhage, and initial visual acuity was hand movement. A submacular blood clot
      of about 4-disc diameter was detected when the vitreous hemorrhage gradually
      cleared. One week after the incident, combined phacoemulsification, intraocular
      lens implantation, pars plana vitrectomy, and submacular clot removal using
      tissue plasminogen activator (tPA) as an adjunct were performed. Recovery was
      uneventful. At the last follow-up 6 months after surgery, best corrected visual
      acuity was 20/30.

PMID- 10946207
TI  - Late traumatic wound dehiscence after phacoemulsification.
AB  - Scars from scleral tunnel or clear corneal incisions for phacoemulsification
      should theoretically be stronger than the larger incisions of planned
      extracapsular cataract extraction. They should also be more resistant to blunt
      trauma. We present a case of scleral tunnel wound dehiscence and expulsion of a
      posterior chamber silicone intraocular lens after blunt trauma.

PMID- 10946208
TI  - FORUM: oxidation and atherosclerosis

PMID- 10946209
TI  - Oxidation and atherosclerosis

PMID- 10946210
TI  - Role of reactive aldehyde in cardiovascular diseases.
AB  - There is increasing evidence that aldehydes generated endogenously during the
      degradation process of biological molecules are involved in many of the
      pathophysiologies associated with cardiovasular diseases such as atherosclerosis
      and the long-term complications of diabetes. Major sources of reactive aldehydes
      in vivo are lipid peroxidation, glycation, and amino acid oxidation. Although the
      types of aldehydes are varied, the important aldehydes that can exert biological
      effects relevant to the pathobiology of oxidant injury are represented by 2
      alkenals, 4-hydroxy-2-alkenals, and ketoaldehydes. These aldehydes exhibit facile
      reactivity with proteins, generating stable products at the end of a series of
      reactions. The protein-bound aldehydes can be detected as constituents not only
      in in vitro oxidized low-density lipoproteins but also in animal models of
      atherosclerosis and in human patients with increased risk factors or clinical
      manifestations of atherosclerosis, indicating that they could indeed be involved
      in the caldiovascular pathology. On the other hand, a number of reactive
      aldehydes have been implicated as inducers in generating intracellular oxidative
      stress and activation of stress signaling pathways, that integrate with other
      signaling pathways to control cellular responses to the extracellular stimuli.

PMID- 10946211
TI  - Regulation of cell growth by oxidized LDL.
AB  - The first reports of the influences of oxidized LDL (oxLDL) on cell function
      pertained to negative effects on cell growth-growth arrest, injury, and toxicity.
      Since these studies, it has become apparent that sublethal levels of oxLDL cause
      some, but not all, cells to proliferate. This review highlights the growth
      promoting effects of oxLDL rather than its inhibitory or injurious effects.
      Smooth muscle cells (SMCs) and monocyte-macrophages proliferate after exposure to
      oxLDL; endothelial cells do not. Scavenger receptors are involved in the
      proliferative effects on monocyte-macrophages, whereas the effects of oxLDL on
      SMCs appear to be receptor independent. Lysophosphatidylcholine (lysoPC), and
      structurally related lipids are among the growth-promoting constituents of oxLDL.
      OxLDL exerts at least a part of its effects by inducing expression or causing the
      release of growth factors. OxLDL (or lysoPC) can cause the release of basic
      fibroblast growth factor (bFGF) from SMCs; oxLDL (or lysoPC) can induce heparin
      binding EGF-like growth factor (HB-EGF) synthesis and release from macrophages.
      An imposing array of changes in cytokine and growth factor expression and/or
      release can be imposed by oxLDL on a wide variety of cell types. These effects
      and the studies probing the cell signaling events leading to them are described.

PMID- 10946212
TI  - Glycoxidation and lipoxidation in atherogenesis.
AB  - Atherosclerosis may be viewed as an age-related disease initiated by
      nonenzymatic, chemical reactions in a biological system. The peroxidation of
      lipids in lipoproteins in the vascular wall leads to local production of reactive
      carbonyl species that mediate recruitment of macrophages, cellular activation and
      proliferation, and chemical modification of vascular proteins by advanced
      lipoxidation end-products (ALEs). The ALEs and their precursors affect the
      structure and function of the vascular wall, setting the stage for atherogenesis.
      The increased risk for atherosclerosis in diabetes may result from additional
      carbonyl production from carbohydrates and additional chemical modification of
      proteins by advanced glycation end-products (AGEs). Failure to maintain
      homeostasis and the increase in oxidizable substrate (lipid) alone, rather than
      oxidative stress, is the likely source of the increase in reactive carbonyl
      precursors and the resultant ALEs and AGEs in atherosclerosis. Nucleophilic AGE
      inhibitors, such as aminoguanidine and pyridoxamine, which trap reactive
      carbonyls and inhibit the formation of AGEs in diabetes, also trap bioactive
      lipids and precursors of ALEs in atherosclerosis. These drugs should be effective
      in retarding the development of atherosclerosis, even in nondiabetic patients.

PMID- 10946213
TI  - Myeloperoxidase-generated oxidants and atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory process where oxidative damage within
      the artery wall is implicated in the pathogenesis of the disease. Mononuclear
      phagocytes, an inflammatory cell capable of generating a variety of oxidizing
      species, are early components of arterial lesions. Their normal functions include
      host defense and surveillance through regulated generation of diffusible radical
      species, reactive oxygen or nitrogen species, and HOCl (hypochlorous acid).
      However, under certain circumstances an excess of these oxidizing species can
      overwhelm local antioxidant defenses and lead to oxidant stress and oxidative
      tissue injury, processes implicated in the pathogenesis of atherosclerosis. This
      review focuses on oxidation reactions catalyzed by myeloperoxidase (MPO), an
      abundant heme protein secreted from activated phagocytes which is present in
      human atherosclerotic lesions. Over the past several years, significant evidence
      has accrued demonstrating that MPO is one pathway for protein and lipoprotein
      oxidation during the evolution of cardiovascular disease. Multiple distinct
      products of MPO are enriched in human atherosclerotic lesions and LDL recovered
      from human atheroma. However, the biological consequences of these MPO-catalyzed
      reactions in vivo are still unclear. Here we discuss evidence for the occurrence
      of MPO-catalyzed oxidation reactions in vivo and the potential role MPO plays in
      both normal host defenses and inflammatory diseases like atherosclerosis.

PMID- 10946214
TI  - Lipoxygenases and atherosclerosis: protection versus pathogenesis.
AB  - 15 lipoxygenase (15LO) is a lipid-oxidizing enzyme that is considered to
      contribute to the formation of oxidized lipids in atherosclerotic lesions.
      Monocyte-macrophages are the key cells that express 15LO in atherosclerotic
      lesions. In this review, we examine the evidence for 15LO involvement in
      atherogenesis and explore and evaluate the potential mechanisms whereby 15LO may
      contribute to the oxidation of LDL by monocyte-macrophages. We also describe
      several possible pro- versus anti-atherogenic functions that may be mediated by
      various products of 15LO lipid oxidation. Central pathways involved in regulating
      15LO expression and activity that may serve as future targets for intervention
      and regulation of this enzyme are also reviewed.

PMID- 10946215
TI  - Ceruloplasmin and cardiovascular disease.
AB  - Transition metal ion-mediated oxidation is a commonly used model system for
      studies of the chemical, structural, and functional modifications of low-density
      lipoprotein (LDL). The physiological relevance of studies using free metal ions
      is unclear and has led to an exploration of free metal ion-independent mechanisms
      of oxidation. We and others have investigated the role of human ceruloplasmin
      (Cp) in oxidative processes because it the principal copper-containing protein in
      serum. There is an abundance of epidemiological data that suggests that serum Cp
      may be an important risk factor predicting myocardial infarction and
      cardiovascular disease. Biochemical studies have shown that Cp is a potent
      catalyst of LDL oxidation in vitro. The pro-oxidant activity of Cp requires an
      intact structure, and a single copper atom at the surface of the protein, near
      His(426), is required for LDL oxidation. Under conditions where inhibitory
      protein (such as albumin) is present, LDL oxidation by Cp is optimal in the
      presence of superoxide, which reduces the surface copper atom of Cp. Cultured
      vascular endothelial and smooth muscle cells also oxidize LDL in the presence of
      Cp. Superoxide release by these cells is a critical factor regulating the rate of
      oxidation. Cultured monocytic cells, when activated by zymosan, can oxidize LDL,
      but these cells are unique in their secretion of Cp. Inhibitor studies using Cp
      specific antibodies and antisense oligonucleotides show that Cp is a major
      contributor to LDL oxidation by these cells. The role of Cp in lipoprotein
      oxidation and atherosclerotic lesion progression in vivo has not been directly
      assessed and is an important area for future studies.

PMID- 10946216
TI  - Indices of lipid peroxidation in vivo: strengths and limitations.
AB  - Oxidant stress has been widely implicated as a mechanism of disease, yet clinical
      trials of antioxidants have not included a biochemical basis for dose selection
      or patient inclusion. Many of the indices traditionally employed to assess lipid
      peroxidation have relied on measurements performed in ex vivo systems of
      questionable relevance to events in vivo. Commonly employed in vivo indices of
      lipid peroxidation are constrained by such issues as the nonspecificity or
      instability of the target anylate, contamination of the anylate by events ex
      vivo, and nonspecificity of analytical methodology. More recently, specific
      methodology based on mass spectrometry has been applied to both 4-hydroxynonenal
      and a variety of isoprostanes in human biological fluids. Measurement of these
      compounds in urine reflects lipid peroxidation in vivo and offers a noninvasive
      approach that may be readily applied to clinical trials.

PMID- 10946217
TI  - Bioactive products of phospholipid oxidation: isolation, identification,
      measurement and activities.
AB  - There is considerable evidence to suggest that oxidation of LDL plays an
      important role in atherogenesis. Polyunsaturated fatty acids, a major oxidative
      target, are present as phospholipids in the outer core of the lipoprotein
      particle. Studies from several laboratories have shown an increase in the levels
      of phospholipid oxidation products in atherosclerotic lesions and of antibodies
      to oxidized phospholipids in mice and humans with lesions. Significantly,
      phospholipid oxidation products have been demonstrated (in vitro) to selectively
      activate processes in vascular wall cells that may contribute to atherogenesis.
      This review discusses activities, methods for isolation, identification and
      measurement of bioactive phospholipids. Past studies suggest that defined and
      relatively simple current technologies allow identification of bioactive
      phospholipid oxidation products and measurement of their levels in tissue.

PMID- 10946218
TI  - Bioactive phospholipid oxidation products.
AB  - Oxidation of phospholipids results in chain-shortened fragments and oxygenated
      derivatives of polyunsaturated sn-2 fatty acyl residues, generating a myriad of
      phospholipid products. Certain oxidation products of phosphatidylcholine bind to
      and activate the human receptor for PAF, and these PAF-like lipids are potent,
      selective inflammatory mediators. Formation of PAF-like lipids is nonenzymatic
      and so their accumulation is unregulated. PAF-like lipids are produced in vivo in
      response to oxidative stresses and are responsible for attendant acute
      inflammatory responses. PAF-like lipids almost exclusively contain an ether
      linked alkyl residue at the sn-1 position of the phosphatidylcholine backbone and
      molecular identification of these is facilitated by phospholipase A(1) treatment
      to remove the bulk of the inactive phospholipids. The identity of biologically
      active species generated by oxidative fragmentation and oxidation can be
      elucidated by understanding relevant reactions leading to the formation of PAF
      like lipids, and then their structure can be established by tandem mass
      spectrometry and chemical synthesis.

PMID- 10946219
TI  - Immunological responses to oxidized LDL.
AB  - Considerable evidence now points to an important role for the immune system in
      experimental models of atherosclerosis. We have reviewed the growing body of
      evidence that oxidation of LDL generates a wide variety of neoself determinants
      that lead to cellular and humoral immune responses. In particular, we have
      demonstrated that at least some of the oxidation-specific epitopes generated on
      the oxidized LDL particle, such as oxidized phospholipid epitopes, are also
      generated on apoptotic cells and are also present on the surface of some
      bacteria. Many of these same epitopes serve as important ligands mediating the
      binding and clearance of oxidatively damaged lipoprotein particles and apoptotic
      cells, and the innate immune response to these epitopes can be seen as a
      concerted response to effect their removal. In addition, other epitopes of OxLDL
      also undoubtedly play a role in the immune activation that characterizes the
      progressive atherosclerotic plaque. It will be of great importance to define the
      importance of the role of these responses and to understand which are beneficial
      and which deleterious. Such information could lead one day to novel therapeutic
      approaches to inhibit atherogenesis that take advantage of the ability to
      manipulate the immune response.

PMID- 10946220
TI  - Cell signaling by reactive nitrogen and oxygen species in atherosclerosis.
AB  - The production of reactive oxygen and nitrogen species has been implicated in
      atherosclerosis principally as means of damaging low-density lipoprotein that in
      turn initiates the accumulation of cholesterol in macrophages. The diversity of
      novel oxidative modifications to lipids and proteins recently identified in
      atherosclerotic lesions has revealed surprising complexity in the mechanisms of
      oxidative damage and their potential role in atherosclerosis. Oxidative or
      nitrosative stress does not completely consume intracellular antioxidants leading
      to cell death as previously thought. Rather, oxidative and nitrosative stress
      have a more subtle impact on the atherogenic process by modulating intracellular
      signaling pathways in vascular tissues to affect inflammatory cell adhesion,
      migration, proliferation, and differentiation. Furthermore, cellular responses
      can affect the production of nitric oxide, which in turn can strongly influence
      the nature of oxidative modifications occurring in atherosclerosis. The dynamic
      interactions between endogenous low concentrations of oxidants or reactive
      nitrogen species with intracellular signaling pathways may have a general role in
      processes affecting wound healing to apoptosis, which can provide novel insights
      into the pathogenesis of atherosclerosis.

PMID- 10946221
TI  - Molecular action of vitamin E in lipoprotein oxidation: implications for
      atherosclerosis.
AB  - The oxidation theory of atherosclerosis proposes that the oxidative modification
      of low-density lipoproteins (LDL) plays a central role in the disease. Although a
      direct causative role of LDL oxidation for atherogenesis has not been
      established, oxidized lipoproteins are detected in atherosclerotic lesions, and
      in vitro oxidized LDL exhibits putative pro-atherogenic activities. alpha
      Tocopherol (alpha-TOH; vitamin E), the major lipid-soluble antioxidant present in
      lipoproteins, is thought to be antiatherogenic. However, results of vitamin E
      interventions on atherosclerosis in experimental animals and cardiovascular
      disease in humans have been inconclusive. Also, recent mechanistic studies
      demonstrate that the role of alpha-TOH during the early stages of lipoprotein
      lipid peroxidation is complex and that the vitamin does not act as a chain
      breaking antioxidant. In the absence of co-antioxidants, compounds capable of
      reducing the alpha-TOH radical and exporting the radical from the lipoprotein
      particle, alpha-TOH exhibits anti- or pro-oxidant activity for lipoprotein lipids
      depending on the degree of radical flux and reactivity of the oxidant. The model
      of tocopherol-mediated peroxidation (TMP) explains the complex molecular action
      of alpha-TOH during lipoprotein lipid peroxidation and antioxidation. This
      article outlines the salient features of TMP, comments on whether TMP is relevant
      for in vivo lipoprotein lipid oxidation, and discusses how co-antioxidants may be
      required to attenuate lipoprotein lipid oxidation in vivo and perhaps
      atherosclerosis.

PMID- 10946222
TI  - The role of natural antioxidants in preserving the biological activity of
      endothelium-derived nitric oxide.
AB  - Endothelium-derived nitric oxide (EDNO) is a pivotal molecule in the regulation
      of vascular tone via the stimulation of vascular smooth muscle cell relaxation
      and concomitant vasodilation. In addition, EDNO exerts a number of other potent
      antiatherogenic effects, including inhibition of leukocyte-endothelial
      interactions, smooth muscle cell proliferation, and platelet aggregation.
      Endothelial vasodilator dysfunction has been observed in patients with CAD or
      coronary risk factors such as hypercholesterolemia, hyperhomocysteinemia,
      essential hypertension, diabetes mellitus, smoking, and aging. Most of these
      conditions are associated with increased oxidative stress, particularly increased
      production of superoxide radicals and elevated levels of oxidized LDL, both of
      which can attenuate the biological activity of EDNO. The levels of superoxide and
      oxidized LDL can be decreased by administering the small molecule antioxidants
      vitamins E and C. Vitamin C also spares intracellular thiols, which in turn can
      stabilize EDNO through the formation of biologically active S-nitrosothiols. Here
      we review the role that vitamins E and C and thiol compounds play in endothelium
      dependent vasodilation. Understanding the mechanisms of the reversal of
      endothelial dysfunction by natural antioxidants will lead to successful
      therapeutic interventions of CAD and its clinical sequelae.

PMID- 10946223
TI  - The oxidative modification hypothesis of atherogenesis: an overview.
AB  - The literature relating lipid and lipoprotein oxidation to atherosclerosis has
      expanded enormously in recent years. Papers on the "oxidative modification
      hypothesis" of atherogenesis have ranged from the most basic studies of the
      chemistry and enzymology of LDL oxidation, through studies of the biological
      effects of oxidized LDL on cultured cells, and on to in vivo studies of the
      effects of antioxidants on atherosclerosis in animals and humans. The data in
      support of this theory are mounting but many key questions remain unanswered. For
      example, while it is generally agreed that LDL undergoes oxidation and that
      oxidized LDL is present in arterial lesions, it is still not known how and where
      LDL gets oxidized in vivo nor which of its many biological effects demonstrable
      in vitro are relevant to atherogenesis in vivo. This brief review is not intended
      to be comprehensive but rather to offer a perspective and a context for this
      Forum. We discuss the strengths and weaknesses of each line of evidence, try to
      identify areas in which further research is needed, assess the relevance of the
      hypothesis to the human disease, and point to some of the potential targets for
      therapy.

PMID- 10946224
TI  - Dancing with the elephants: envisioning the structural biology of DNA repair
      pathways.

PMID- 10946225
TI  - DNA photolyases and cryptochromes.
AB  - This brief review gives an overview of the gene family of photolyases and
      cryptochromes, followed by a description of the main features of the three
      dimensional structures of photolyases known to date. It then discusses recent
      biophysical studies of photolyase function, and modelling studies on the
      interaction between the enzyme and its substrate.

PMID- 10946226
TI  - Conserved structural motifs governing the stoichiometric repair of alkylated DNA
      by O(6)-alkylguanine-DNA alkyltransferase.
AB  - O(6)-alkylguanine-DNA alkyltransferase (AGT) directly repairs alkylation damage
      at the O(6)-position of guanine in a unique, stoichiometric reaction. Crystal
      structures of AGT homologs from the three kingdoms of life reveal that despite
      their extremely low primary sequence homology, the topology and overall structure
      of AGT has been remarkably conserved. The C-terminal domain of the two-domain,
      alpha/beta fold bears a helix-turn-helix (HTH) motif that has been implicated in
      DNA-binding by structural and mutagenic studies. In the second helix of the HTH,
      the recognition helix, lies a conserved RAV[A/G] motif, whose "arginine finger"
      promotes flipping of the target nucleotide from the base stack. Recognition of
      the extrahelical guanine is likely predominantly through interactions with the
      protein backbone, while hydrophobic sidechains line the alkyl-binding pocket, as
      defined by product complexes of human AGT. The irreversible dealkylation reaction
      is accomplished by an active-site cysteine that participates in a hydrogen bond
      network with invariant histidine and glutamic acid residues, reminiscent of the
      serine protease catalytic triad. Structural and biochemical results suggest that
      cysteine alkylation opens the domain-interfacing "Asn-hinge", which couples the
      active-site to the recognition helix, providing both a mechanism for release of
      repaired DNA and a signal for the observed degradation of alkylated AGT.

PMID- 10946227
TI  - Structure and function in the uracil-DNA glycosylase superfamily.
AB  - Deamination of cytosine to uracil is one of the major pro-mutagenic events in
      DNA, causing G:C-->A:T transition mutations if not repaired before replication.
      Repair of uracil-DNA is achieved in a base-excision pathway initiated by a uracil
      DNA glycosylase (UDG) enzyme of which four families have so far been identified.
      Family-1 enzymes are active against uracil in ssDNA and dsDNA, and recognise
      uracil explicitly in an extrahelical conformation via a combination of protein
      and bound-water interactions. Extrahelical recognition requires an efficient
      process of substrate location by 'base-sampling' probably by hopping or gliding
      along the DNA. Family-2 enzymes are mismatch specific and explicitly recognise
      the widowed guanine on the complementary strand rather than the extrahelical
      scissile pyrimidine. This allows a broader specificity so that some Family-2
      enzymes can excise uracil and 3, N(4)-ethenocytosine from mismatches with
      guanine. Although structures are not yet available for Family-3 (SMUG) and Family
      4 enzymes, sequence analysis suggests similar overall folds, and identifies
      common active site motifs but with a surprising lack of conservation of catalytic
      residues between members of the super-family.

PMID- 10946228
TI  - Lessons learned from structural results on uracil-DNA glycosylase.
AB  - Uracil-DNA glycosylase (UDG) functions as a sentry guarding against uracil in
      DNA. UDG initiates DNA base excision repair (BER) by hydrolyzing the uracil base
      from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and
      complete functional mechanism is emerging that combines structural and
      biochemical results. This functional mechanism addresses the detection of uracil
      bases within a vast excess of normal DNA, the features of the enzyme that drive
      catalysis, and coordination of UDG with later steps of BER while preventing the
      release of toxic intermediates. Many of the solutions that UDG has evolved to
      overcome the challenges of policing the genome are shared by other DNA
      glycosylases and DNA repair enzymes, and thus appear to be general.

PMID- 10946229
TI  - Structural studies of human alkyladenine glycosylase and E. coli 3-methyladenine
      glycosylase.
AB  - Human alkyladenine glycosylase (AAG) and Escherichia coli 3-methyladenine
      glycosylase (AlkA) are base excision repair glycosylases that recognize and
      excise a variety of alkylated bases from DNA. The crystal structures of these
      enzymes have provided insight into their substrate specificity and mechanisms of
      catalysis. Both enzymes utilize DNA bending and base-flipping mechanisms to
      expose and bind substrate bases. Crystal structures of AAG complexed to DNA
      suggest that the enzyme selects substrate bases through a combination of hydrogen
      bonding and the steric constraints of the active site, and that the enzyme
      activates a water molecule for an in-line backside attack of the N-glycosylic
      bond. In contrast to AAG, the structure of the AlkA-DNA complex suggests that
      AlkA substrate recognition and catalytic specificity are intimately integrated in
      a S(N)1 type mechanism in which the catalytic Asp238 directly promotes the
      release of modified bases.

PMID- 10946230
TI  - Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA
      base excision repair: the 3' ends justify the means.
AB  - DNA damage occurs unceasingly in all cells. Spontaneous DNA base loss, as well as
      the removal of damaged DNA bases by specific enzymes targeted to distinct base
      lesions, creates non-coding and lethal apurinic/apyrimidinic (AP) sites. AP sites
      are the central intermediate in DNA base excision repair (BER) and must be
      processed by 5' AP endonucleases. These pivotal enzymes detect, recognize, and
      cleave the DNA phosphodiester backbone 5' of, AP sites to create a free 3'-OH end
      for DNA polymerase repair synthesis. In humans, AP sites are processed by APE1,
      whereas in yeast the primary AP endonuclease is termed APN1, and these enzymes
      are the major constitutively expressed AP endonucleases in these organisms and
      are homologous to the Escherichia coli enzymes Exonuclease III (Exo III) and
      Endonuclease IV (Endo IV), respectively. These enzymes represent both of the
      conserved 5' AP endonuclease enzyme families that exist in biology. Crystal
      structures of APE1 and Endo IV, both bound to AP site-containing DNA reveal how
      abasic sites are recognized and the DNA phosphodiester backbone cleaved by these
      two structurally unrelated enzymes with distinct chemical mechanisms. Both
      enzymes orient the AP-DNA via positively charged complementary surfaces and
      insert loops into the DNA base stack, bending and kinking the DNA to promote
      flipping of the AP site into a sequestered enzyme pocket that excludes undamaged
      nucleotides. Each enzyme-DNA complex exhibits distinctly different DNA
      conformations, which may impact upon the biological functions of each enzyme
      within BER signal-transduction pathways.

PMID- 10946231
TI  - Structural design of a eukaryotic DNA repair polymerase: DNA polymerase beta.
AB  - DNA polymerase beta, the smallest eukaryotic DNA polymerase, is designed to
      synthesize DNA in short DNA gaps during DNA repair. It is composed of two
      specialized domains that contribute essential enzymatic activities to base
      excision repair (BER). Its amino-terminal domain possesses a lyase activity
      necessary to remove the 5'-deoxyribose phosphate (dRP) intermediate generated
      during BER. Removal of the dRP moiety is often the rate-limiting step during BER.
      Failure to remove this group may initiate alternate BER pathways. The larger
      polymerase domain has nucleotidyl transferase activity. This domain has a modular
      organization with sub-domains that bind duplex DNA, catalytic metals, and the
      correct nucleoside triphosphate in a template-dependent manner. X-ray crystal
      structures of DNA polymerase beta, with and without bound substrates, has
      inferred that domain, sub-domain, and substrate conformational changes occur upon
      ligand binding. Many of these conformational changes are distinct from those
      observed in structures of other DNA polymerases. This review will examine the
      structural aspects of DNA polymerase beta that facilitate its role in BER.

PMID- 10946232
TI  - Structure and function of mismatch repair proteins.
AB  - DNA mismatch repair is required for maintaining genomic stability and is highly
      conserved from prokaryotes to eukaryotes. Errors made during DNA replication,
      such as deletions, insertions and mismatched basepairs, are substrates for
      mismatch repair. Mismatch repair is strand-specific and targets only the newly
      synthesized daughter strand. To initiate mismatch repair in Escherichia coli,
      three proteins are essential, MutS, for mismatch recognition, MutH, for
      introduction of a nick in the target strand, and MutL, for mediating the
      interactions between MutH and MutS. Homologues of MutS and MutL important for
      mismatch repair have been found in nearly all organisms. Mutations in MutS and
      MutL homologues have been linked to increased cancer susceptibility in both mice
      and humans. Here, we review the crystal structures of the MutH endonuclease, a
      conserved ATPase fragment of MutL (LN40), and complexes of LN40 with various
      nucleotides. Based on the crystal structure, the active site of MutH has been
      identified and an evolutionary relationship between MutH and type II restriction
      endonucleases established. Recent crystallographic and biochemical studies have
      revealed that MutL operates as a molecular switch with its interactions with MutH
      and MutS regulated by ATP binding and hydrolysis. These crystal structures also
      shed light on the general mechanism of mismatch repair and the roles of Mut
      proteins in preventing mutagenesis.

PMID- 10946233
TI  - Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V,
      E. coli Vsr protein, and human nucleotide excision repair factor XPA.
AB  - Genetic information is frequently disturbed by introduction of modified or
      mismatch bases into duplex DNA, and hence all organisms contain DNA repair
      systems to restore normal genetic information by removing such damaged bases or
      nucleotides and replacing them by correct ones. The understanding of this repair
      mechanism is a central subject in cell biology. This review focuses on the three
      dimensional structural views of damaged DNA recognition by three proteins. The
      first protein is T4 endonuclease V (T4 endo V), which catalyzes the first
      reaction step of the excision repair pathway to remove pyrimidine-dimers (PD)
      produced within duplex DNA by UV irradiation. The crystal structure of this
      enzyme complexed with DNA containing a thymidine-dimer provided the first direct
      view of DNA lesion recognition by a repair enzyme, indicating that the DNA kink
      coupled with base flipping-out is important for damaged DNA recognition. The
      second is very short patch repair (Vsr) endonuclease, which recognizes a TG
      mismatch within the five base pair consensus sequence. The crystal structure of
      this enzyme in complex with duplex DNA containing a TG mismatch revealed a novel
      mismatch base pair recognition scheme, where three aromatic residues intercalate
      from the major groove into the DNA to strikingly deform the base pair stacking
      but the base flipping-out does not occur. The third is human nucleotide excision
      repair (NER) factor XPA, which is a major component of a large protein complex.
      This protein has been shown to bind preferentially to UV- or chemical carcinogen
      damaged DNA. The solution structure of the XPA central domain, essential for the
      interaction of damaged DNA, was determined by NMR. This domain was found to be
      divided mainly into a (Cys)4-type zinc-finger motif subdomain for replication
      protein A (RPA) recognition and the carboxyl terminal subdomain responsible for
      DNA binding.

PMID- 10946234
TI  - The nucleotide excision repair protein UvrB, a helicase-like enzyme with a catch.
AB  - Nucleotide excision repair (NER) is a universal DNA repair mechanism found in all
      three kingdoms of life. Its ability to repair a broad range of DNA lesions sets
      NER apart from other repair mechanisms. NER systems recognize the damaged DNA
      strand and cleave it 3', then 5' to the lesion. After the oligonucleotide
      containing the lesion is removed, repair synthesis fills the resulting gap. UvrB
      is the central component of bacterial NER. It is directly involved in
      distinguishing damaged from undamaged DNA and guides the DNA from recognition to
      repair synthesis. Recently solved structures of UvrB from different organisms
      represent the first high-resolution view into bacterial NER. The structures
      provide detailed insight into the domain architecture of UvrB and, through
      comparison, suggest possible domain movements. The structure of UvrB consists of
      five domains. Domains 1a and 3 bind ATP at the inter-domain interface and share
      high structural similarity to helicases of superfamilies I and II. Not related to
      helicase structures, domains 2 and 4 are involved in interactions with either
      UvrA or UvrC, whereas domain 1b was implicated for DNA binding. The structures
      indicate that ATP binding and hydrolysis is associated with domain motions.
      UvrB's ATPase activity, however, is not coupled to the separation of long DNA
      duplexes as in helicases, but rather leads to the formation of the preincision
      complex with the damaged DNA substrate. The location of conserved residues and
      structural comparisons with helicase-DNA structures suggest how UvrB might bind
      to DNA. A model of the UvrB-DNA interaction in which a beta-hairpin of UvrB
      inserts between the DNA double strand has been proposed recently. This padlock
      model is developed further to suggest two distinct consequences of domain motion:
      in the UvrA(2)B-DNA complex, domain motions lead to translocation along the DNA,
      whereas in the tight UvrB-DNA pre-incision complex, they lead to distortion of
      the 3' incision site.

PMID- 10946235
TI  - DNA ligases in the repair and replication of DNA.
AB  - DNA ligases are critical enzymes of DNA metabolism. The reaction they catalyse
      (the joining of nicked DNA) is required in DNA replication and in DNA repair
      pathways that require the re-synthesis of DNA. Most organisms express DNA ligases
      powered by ATP, but eubacteria appear to be unique in having ligases driven by
      NAD(+). Interestingly, despite protein sequence and biochemical differences
      between the two classes of ligase, the structure of the adenylation domain is
      remarkably similar. Higher organisms express a variety of different ligases,
      which appear to be targetted to specific functions. DNA ligase I is required for
      Okazaki fragment joining and some repair pathways; DNA ligase II appears to be a
      degradation product of ligase III; DNA ligase III has several isoforms, which are
      involved in repair and recombination and DNA ligase IV is necessary for V(D)J
      recombination and non-homologous end-joining. Sequence and structural analysis of
      DNA ligases has shown that these enzymes are built around a common catalytic
      core, which is likely to be similar in three-dimensional structure to that of T7
      bacteriophage ligase. The differences between the various ligases are likely to
      be mediated by regions outside of this common core, the structures of which are
      not known. Therefore, the determination of these structures, along with the
      structures of ligases bound to substrate DNAs and partner proteins ought to be
      seen as a priority.

PMID- 10946237
TI  - Genotoxicity evaluation of heat shock in gold fish (Carassius auratus).
AB  - Genotoxicity evaluation of heat shock was carried out in Carassius auratus. The
      genotoxicity end points studied were nuclear anomalies (micronucleus assay),
      chromosomal aberrations, DNA damage (comet assay) and cell proliferation. The
      heat shock temperatures used were 34 degrees C, 36 degrees C and 38 degrees C.
      The results demonstrated that heat shock causes the induction of micronucleus at
      all the three temperature studied. Heat shock also inhibited cell proliferation
      at 38 degrees C and caused aberrations in the metaphase chromosomes at 34 degrees
      C and 36 degrees C. Comet assay demonstrated single strand DNA damage at all the
      three temperatures. The results obtained indicate that heat shock is a
      genotoxicant.

PMID- 10946236
TI  - The BRCA1 C-terminal domain: structure and function.
AB  - The BRCA1 C-terminal region contains a duplicated globular domain termed BRCT
      that is found within many DNA damage repair and cell cycle checkpoint proteins.
      The unique diversity of this domain superfamily allows BRCT modules to interact
      forming homo/hetero BRCT multimers, BRCT-non-BRCT interactions, and interactions
      with DNA strand breaks. The sequence and functional diversity of the BRCT
      superfamily suggests that BRCT domains are evolutionarily convenient interaction
      modules.

PMID- 10946238
TI  - Effect of acyclovir on the radiation-induced micronuclei and cell death.
AB  - Treatment of HeLa cells with 0.1 microM Acyclovir [9-(2
      hydroxyethoxymethyl)guanine] (ACV) before exposure to 0, 0.25, 0.5, 1, 2 and 3 Gy
      of gamma-radiation resulted in a dose-dependent decline in the growth kinetics
      and cell proliferation indices at 20, 30 and 40 h post-irradiation when compared
      with the PBS+irradiation group. These results were reflected in the cell
      survival, which declined in a dose-dependent manner and the surviving fraction of
      cells was significantly lower in ACV+irradiation group than that of
      PBS+irradiation group. The effect of ACV+1 Gy irradiation was almost similar to
      PBS+3 Gy irradiation suggesting an enhancement of the radiation effect by ACV
      pretreatment. The frequency of micronuclei increased in a dose-dependent manner
      at all the post-irradiation time periods in both PBS+irradiation and
      ACV+irradiation group and it was significantly elevated in the latter when
      compared with the former group. The dose-response for both groups was linear. The
      surviving fraction of HeLa cells declined with the increasing MN frequency and a
      close linear quadratic correlation between cell survival and micronuclei
      induction was observed.

PMID- 10946239
TI  - ENU induces mutations in the heart of lacZ transgenic mice.
AB  - The use of transgenic mouse models as somatic mutation assays allows
      determination of mutation in all tissues of the mouse, including non-dividing
      tissues. In this regard, these models can be used to study the possibility that
      mutations can be induced in mitotically quiescent organs such as the heart.
      Mutations are generally thought to be associated with mitotic processes of DNA
      replication. Mutations, however, are also postulated to occur in the absence of
      mitosis as the result of DNA repair. In order to determine whether or not
      mutations could be induced in the heart, we analyzed the mutant frequency in the
      hearts of F(1) (Muta Mouse X SWR) mice that had been treated acutely with 250
      mg/kg ENU and sampled at days 10, 35, and 70 post-treatment. A significant
      increase in mutant frequency at day 70 shows that mutations can be induced in the
      heart. Since the heart contains small numbers of non-muscle cells, additional
      mechanisms that could explain these results were also considered. The effect of
      ENU-induced cell proliferation or a sub-population of rapidly dividing cells is
      ruled out by C(14)-thymidine uptake studies which showed minimal proliferation.
      By the same token, the influence of ex vivo mutations (i.e., DNA adducts fixed as
      mutations during replication in the bacteria) is ruled out by the observed time
      course of mutations, as well as experimental evidence showing that such mutations
      are not detected in the lacZ assay.

PMID- 10946240
TI  - Aneugenic effects of some metal compounds assessed by chromosome counting in MRC
      5 human cells.
AB  - Development of a comprehensive test battery is necesary for the evaluation and
      detection of aneugenic chemicals. The chromosome couting method was used in the
      present study. The aneugenic ability of cadmium choride (1.0, 2.0 and 4.0x10(-3)
      mM), cadmium sulfate (3. 3, 6.7x10(-5) and 1.3x10(-4) mM), potassium dichromate
      (2.5, 5. 0x10(-4) and 1.0x10(-3) mM) and cacodilic acid (1.25, 2.5 and 5. 0x10(
      2) mM) were analysed using MRC-5 cells which have a modal diploid number of 2
      n=46 with a spontaneous aneuploid or polyploid cells not higher than 13% and 8%,
      respectively.All compounds induced significant increments of aneuploid cells in
      relation to negative controls. The frequency of aneuploid cells increased in all
      treatments with cadmium chloride. Cadmium sulfate induced significant increments
      of aneuploid cells with the two higher doses. All the doses of potassium
      dichromate increased the frequency of aneuploid cells although to a lesser degree
      than the other compounds. In these cases, differences were in the borderline of
      statistical significance (p<0.05). Moreover, a low number of cells could be
      analysed in treatments with the highest dose due to the decrease in the mitotic
      index. Results obtained are coincident with previous reports using the same
      methodology in the sense that induced aneuploidy was mainly evidenced by the
      increase of hypodiploid but not hyperdiploid cells. In addition, anaphase
      telophase analysis of the effects of the same doses of these metal compounds in
      CHO cells showed significant increments of lagging chromosomes and increased
      frequencies of kinetochore positive micronuclei in MRC-5 cells. These findings
      could be considered as an indication that the main cause of unequal chromosome
      separation is the failure of kinetochores to attach the spindle apparatus either
      by alteration of its protein components or by the altered chromatid separation in
      anaphase.

PMID- 10946241
TI  - Chemical and mutagenic properties of asphalt fume condensates generated under
      laboratory and field conditions.
AB  - Exposure to asphalt fumes is widely recognized as a potential occupational health
      concern for paving and roofing workers. Two studies suggest that asphalt fumes
      generated in the laboratory are carcinogenic to mice. In this study, asphalt fume
      condensate (AFC) was collected from the head space of an operating hot mix
      asphalt storage tank and from a laboratory fume-generating apparatus operating at
      approximately 149 degrees C and 316 degrees C. Salmonella assays for mutagenesis,
      in vitro chromosomal aberration assays using Chinese hamster ovary (CHO) cells,
      chemical analyses, and simulated distillations were performed using gas
      chromatography to characterize the toxicological and chemical properties of AFCs
      generated by these two methods. The 316 degrees C lab AFC sample was more
      mutagenic in the Salmonella assay than the 149 degrees C lab AFC sample, with
      mutagenicity indices (MIs) of 8.3 and 5.3, respectively. AFCs collected from the
      storage tank were not mutagenic. Chromosomal aberration assays of all AFCs were
      negative. Chemical analyses and simulated distillations showed substantial
      differences in the chemical composition of the AFC samples. The 316 degrees C lab
      AFC sample contained more higher-boiling-point (three- and four-ring) polycyclic
      aromatic sulfur heterocycle compounds than the 149 degrees C lab AFC sample, and
      both lab AFC samples contained 5 to 100 times more of these compounds than AFC
      samples collected from the asphalt storage tank. These results are consistent
      with other data reported in the scientific literature describing the
      carcinogenicity of higher-boiling-point sulfur heterocycle compounds. In contrast
      to other recent studies, the results of this study indicate that the chemical
      composition and toxicological properties of laboratory-generated asphalt fumes
      are not representative of those properties of fumes to which workers and the
      public might be exposed.

PMID- 10946242
TI  - Hydrogen peroxide induced mutations at the HPRT locus in primary human T
      lymphocytes.
AB  - Reactive oxygen species (ROS) produced by intracellular metabolism are believed
      to contribute to spontaneous mutagenesis in somatic cells. Hydrogen peroxide
      (H(2)O(2)) has been shown to induce a variety of genetic alterations, probably by
      the generation of hydroxyl radicals via the Fenton reaction. The kinds of DNA
      sequence alterations caused by H(2)O(2) in prokaryotic cells have been studied
      extensively, whereas relatively little is known about the mutational spectrum
      induced by H(2)O(2) in mammalian genes. We have used the T-cell cloning assay to
      study the ability of H(2)O(2) to induce mutations at the hypoxanthine guanine
      phosphoribosyltransferase (HPRT) locus in primary human lymphocytes. Treatment of
      cells for 1 h with 0.34-1.35 mM of H(2)O(2) caused a dose dependent decrease of
      cell survival and increase of the HPRT mutant frequency (MF). After 8 days of
      expression time, the highest dose of H(2)O(2) caused a 5-fold increase of MF
      compared to the untreated control cells. Mutant clones were collected and the
      genomic rearrangements at the T-cell receptor (TCR) gamma-locus were studied to
      identify independent mutations. RT-PCR and DNA sequencing was used to identify
      mutations in the HPRT coding region. Due to a relatively high frequency of
      sibling clones, only six independent mutations were obtained among the controls,
      and 20 among the H(2)O(2) treated cells. In both sets, single base pair
      substitutions were the most common type of mutation (5/6 and 13/20,
      respectively), with a predominance of transitions at GC base pairs, which is also
      the most common type of HPRT mutation in T-cells in vivo. Among the single base
      pair substitutions, five were new mutations not previously reported in the human
      HPRT mutation database. Overall, the kinds of mutation occurring in T-cells in
      vivo and H(2)O(2) treated cells were similar, albeit the number of mutants was
      too small to allow a meaningful statistical comparison. These results demonstrate
      that H(2)O(2) is mutagenic to primary human T-lymphocytes in vitro and induces
      mutations of the same kind that is observed in the background spectrum of HPRT
      mutation in T-cells in vivo.

PMID- 10946243
TI  - Micronuclei in lymphocytes of prostate cancer patients undergoing radiation
      therapy.
AB  - To further verify the applicability of the micronucleus (MN) assay in
      biodosimetry, we measured the MN yield in cytokinesis-blocked (CB) peripheral
      blood lymphocytes (PBL) of eight prostate cancer (PC) patients. These patients
      had no previous chemotherapy or radiotherapy (xRT). They were treated with
      standardized schemes of fractionated pelvic xRT. Before xRT, and at one random
      time-point during the course of xRT, blood samples were collected from each
      patient for the following purposes: (1) to verify the relationship between the MN
      yield in PBL and the estimated equivalent (EQ) total-body absorbed dose; and (2)
      to evaluate the individual differences of ex vivo radiation dose-response (1-4
      Gy) relationship of MN yield in PBL before xRT. The number of xRT fractions,
      cumulative tumor dose, and EQ total-body absorbed doses of these patients
      represented a wide range. We found in PBL of these patients that (1) MN yield (Y)
      increased linearly with the estimated EQ total-body absorbed dose as Y=14.6+9.2D
      (R(2)=0.7, p=0.007); the distributions of MN yield were overdispersed; the ratio
      of relative increment of MN yield per 1000 binucleated (BN) PBL ranged from 0.9
      to 8.2 (median: 4.1) folds above that of the respective baseline levels; and (2)
      before xRT, the MN yields also increased linearly with the ex vivo radiation
      dose; at each radiation dose level, the distributions of MN yield were
      overdispersed in most patients. In two of the three patients with xRT-induced
      early side effects (cystitis, diarrhea), the MN yield in PBL induced by ex vivo
      irradiation before xRT was significantly higher than in the other patients
      without xRT-induced side effects. These findings suggest that MN yields in CB PBL
      can be used as an in vivo biodosimeter. Since the differences in individual ex
      vivo radiation dose-response relationship of MN yield in PBL before xRT appeared
      to be significant, our preliminary results also suggest that it may be possible
      to identify individual intrinsic radiosensitivity before the start of xRT.

PMID- 10946244
TI  - Genotoxicity of urban air pollutants in the Czech Republic. Part I. Bacterial
      mutagenic potencies of organic compounds adsorbed on PM10 particulates.
AB  - As part of a long-term program to investigate the impact of air pollution on the
      health of a population in a polluted region in Northern Bohemia, mutagenicity of
      extractable organic matter (EOM) from air particles PM10 was investigated by the
      means of Salmonella typhimurium indicator strains TA98 and YG1041 using the Ames
      plate incorporation assay. The air samples were collected in both the polluted
      and the control districts during the summers and winters of 1993-1994. In the
      polluted district, the collection was repeated during the winter of 1996-1997.
      The crude extracts from filters pooled according to the locality and the season
      were fractionated by acid-base partitioning into acid, base, and neutral
      fractions. The neutral fractions were further fractionated by silica gel column
      chromatography into five subfractions. The induction of revertants with the crude
      extracts was higher in winter samples than in summer samples. Both indirect
      acting and direct-acting mutagenicity were observed. The indirect mutagenic
      potency of aromatic subfractions containing polycyclic aromatic hydrocarbons
      (PAHs) was generally low. The mutagenic potency detected with TA98 was more
      distinct only in the winter sample 1993-1994 from the polluted area, where the
      aromatic subfraction accounted for 23% of total mutagenicity. In both strains,
      the highest direct-acting mutagenicity was found in slightly polar fractions
      containing nitro-PAHs. The mutagenic potency detected with YG1041 was about two
      orders of magnitude higher than that detected with TA98. No substantial
      locational- or time-related variances in the mutagenic potencies of EOM, or in
      the spectrum of chemical components identified in individual fractions were
      found. The polluted district, in comparison to the control district, was found to
      have higher amounts of EOM, carcinogenic PAHs and mutagenicity of air particles
      (rev/m(3)). The fractionating process, combined with the bacterial mutagenicity
      test, confirmed that nitro-derivatives are the most important contributors to the
      bacterial mutagenicity of air particles. However, this study did not fulfill the
      expectancy to bring substantially new, clear-cut information on the composition
      and the biological activity of air pollution in both districts.

PMID- 10946245
TI  - Genotoxicity of urban air pollutants in the Czech Republic. Part II. DNA adduct
      formation in mammalian cells by extractable organic matter.
AB  - The study was aimed at determining the genotoxic potential of extractable organic
      matter (EOM) from ambient air particles PM10 (<10 micrometer) using mammalian
      cells in culture as test system. Air samples were collected in the course of
      summer and winter periods in two regions of the Czech Republic representing low
      and high levels of air pollution, the districts of industrial Teplice and rural
      Prachatice, respectively. EOM was fractionated by acid-base partitioning and
      silica gel column chromatography. Aliquots of fractions were incubated with
      cultured hepatocytes derived from male rats or Chinese hamster lung V79NH cells
      expressing nitroreductase activity but virtually no cytochrome P450 activity. DNA
      adduct levels were analyzed by 32P-postlabeling using butanol extraction for
      adduct enrichment. In hepatocytes, crude extracts caused the formation of
      substantial amounts of DNA reactive material being detectable in a broad diagonal
      radioactive zone (DRZ) in the chromatograms. Highest DNA adduct levels were found
      in the aromatic fractions and slightly polar fractions which contain most of the
      polycyclic aromatic hydrocarbons (PAH) and nitro-substituted PAH (nitro-PAH),
      respectively, comprising 75-90% of total adducts. This partitioning was
      independent of the sampling period and locality. In agreement with the higher
      average ambient air concentrations of PAH in the winter than the summer, 3-4-fold
      higher DNA adduct levels were detected in extracts sampled in the winter.
      Calculated on the basis of EOM/m(3), DNA adduct levels of samples collected in
      winter period were 10-fold higher than those collected in the summer period and 2
      fold higher in Teplice than in Prachatice. Pretreatment of hepatocytes with
      2,3,7,8-tetrachlorodibenzo-p-dioxin decreased DNA binding by 50-75%. In contrast
      to the findings in hepatocytes, in V79NH cells about 80% of the DNA adducts were
      caused by material in the slightly polar fractions appearing as distinct spots in
      the radiochromatograms. Seasonal variation of DNA adducts in V79NH cells was
      greater than variation between localities. Our results suggest that PAH as well
      as nitro-PAH are the main contributors to the genotoxicity of EOM derived from
      both industrial and rural areas. The results, furthermore, indicate that analysis
      of DNA adducts in mammalian cells in culture offers a suitable method for
      monitoring the genotoxicity of complex mixtures of environmental chemicals.

PMID- 10946246
TI  - Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia,
      inducing primarily deletions.
AB  - Dominant-lethal tests [P.D. Sudman, J.C. Rutledge, J.B. Bishop, W.M. Generoso,
      Bleomycin: female-specific dominant lethal effects in mice, Mutat. Res. 296
      (1992) 205-217] had suggested that Bleomycin sulfate (Blenoxane), BLM, might be a
      female-specific mutagen. While confirming that BLM is indeed a powerful inducer
      of dominant-lethal mutations in females that fails to induce such mutations in
      postspermatogonial stages of males, we have shown in a specific-locus test that
      BLM is, in fact, mutagenic in males. This mutagenicity, however, is restricted to
      spermatogonia (stem-cell and differentiating stages), for which the specific
      locus mutation rate differed significantly (P<0.008) from the historical control
      rate. In treated groups, dominant mutations, also, originated only in
      spermatogonia. With regard to mutation frequencies, this germ-cell-stage pattern
      is different from that for radiation and for any other chemical studied to date,
      except ethylnitrosourea (ENU). However, the nature of the spermatogonial specific
      locus mutations differentiates BLM from ENU as well, because BLM induced
      primarily (or, perhaps, exclusively) multilocus deletions. Heretofore, no
      chemical that induced specific-locus mutations in spermatogonia did not also
      induce specific-locus as well as dominant-lethal mutations in postspermatogonial
      stages, making the dominant lethal test, up till now, predictive of male
      mutagenicity in general. The BLM results now demonstrate that there are chemicals
      that can induce specific-locus mutations in spermatogonia without testing
      positive in postspermatogonial stages. Thus, BLM, while not female-specific, is
      unique, (a) in its germ-cell-stage specificity in males, and (b) in inducing a
      type of mutation (deletions) that is atypical for the responding germ-cell stages
      (spermatogonia).

PMID- 10946247
TI  - Phenolic acids inhibit chloroplast mutagenesis in Euglena gracilis.
AB  - The mutagenicity (bleaching activity) of ofloxacin (43 microM) and acridine
      orange (AO) (13.5 microM) in Euglena gracilis is inhibited by plant phenolics.
      Caffeic acid (CA), p-coumaric acid (PCA), ferulic acid (FA) and gentisic acid
      (GA) (25, 50, 100 and 250 microM) exhibited a significant concentration-dependent
      inhibitory effect against ofloxacin-induced mutagenicity, which was very
      effectively eliminated by the highest concentration of all four of those phenolic
      acids. The mutagenicity of AO was also significantly reduced in the presence of
      CA, PCA and FA (25, 50, 100 and 250 microM). However, GA exhibited no significant
      activity, even at the concentration of 250 microM. Based on the UV
      spectrophotometric measurements, we suggest that the antimutagenic effect of CA,
      PCA, FA and GA resulted from the scavenging of reactive oxygen species (ROS)
      produced by ofloxacin. On the other hand, the reduction of AO-induced
      mutagenicity correlates with the binding capabilities of CA, PCA and FA, with the
      exception of GA.

PMID- 10946249
TI  - Association between activated K-ras and c-erbB-2 oncogenes with "high-risk" and
      "low-risk" human papilloma virus types in preinvasive cervical lesions.
AB  - Clinical and epidemiological data have linked cervical cancer to the Human
      Papilloma Virus (HPV) infection. However, the presence of HPV infection alone is
      not enough to cause tumorigenesis, suggesting a role for additional host-cell
      genetic factors. The aim of the present work was to study the association of K
      ras and c-erbB-2 mutations in cervical tissue samples with different grades of
      dysplasia and infected with HPV-6 ("low-risk" type) or HPV-16 and HPV-18 ("high
      risk" types). Negative HPV-DNA samples were used as controls. The detection of K
      ras and c-erbB-2 activation were performed by Artificial Refractory Mutation
      System (ARMS)-PCR and semiquantitative PCR, respectively. Statistical analysis
      showed a highly significant difference in K-ras codon 12 mutation frequency
      between high-risk and low-risk HPV-infected samples (p<0.05). On the other hand,
      amplification of the c-erbB-2 oncogene appeared associated to tissue samples
      infected with HPV-6 (p<0.003). Cervical carcinoma appears to arise from a series
      of well-characterized progressive histological changes, but the genetic
      alterations necessary for cervical tumorigenesis are not yet clear. These results
      raise the possibility for a role of certain proto-oncogenes and their activation
      in cervical neoplasia.

PMID- 10946248
TI  - The mutagenic spectrum of acridine-linked aniline nitrogen mustards in AS52
      cells: implications of DNA targeting with high selectivity for adenine or guanine
      bases.
AB  - The mutational spectra generated in AS52 cells at the gpt gene locus by aniline
      mustards were studied by the isolation of resistant clones and sequencing of the
      altered gene. A set of four aniline mustards (both mono- and bifunctional) linked
      to a DNA-affinic 9-aminoacridine (9-AA) carrier was used, together with the
      untargeted mustards chlorambucil (CHL) and its half-mustard, and the DNA binding
      carrier, 9-AA. Both 9-AA and CHL were weak cytotoxins, with the DNA-targeted
      mustards being markedly (10-40-fold) more dose potent, and the bifunctional ones
      somewhat more toxic than the monofunctional ones. 9-AA produced a different
      spectrum of mutations to the spontaneous background, with more minor addition
      events and less base pair substitutions, and showing for the first time that
      frameshift events so characteristic of 9-AA in bacteria or bacteriophage also
      occur in mammalian cells. The mutational spectra of the DNA-targeted mustards
      were quite different both from this and from the lesions caused by the untargeted
      mustards, which cause largely transition mutations at AT sites (despite a clear
      preference for formation of N(7)-guanine adducts). There were very few transition
      mutations, suggesting that the initial O(6)-alkylguanine/O(4)-alkylthymine
      lesions considered to give rise to these are relatively rare. There was also a
      lower incidence of complete deletions, usually attributed to DNA cross-links. For
      the short chain length targeted mustards, which form initial stable adducts
      largely (95%) at guanine N(7) sites, base pair substitution mutations,
      predominantly transversions, involved AT and GC base pairs equally. In contrast,
      the longer chain length targeted mustards, which form >90% of initial adducts at
      adenine N(1) sites, generated also formed transversion mutations, but these
      overwhelmingly (24/27) involved AT base pairs.

PMID- 10946251
TI  - Equal induction and persistence of chromosome aberrations involving chromosomes
      1, 4 and 10 in thyroid cancer patients treated with radioactive iodine.
AB  - A number of in vitro studies have questioned the assumption of random
      distribution of breaks in radiation-induced chromosome aberrations. The
      therapeutic application of radioactive 131I in thyroid cancer patients offers a
      good opportunity to study the induction and persistence of cytogenetic damage
      involving different chromosomes in vivo. Using whole-chromosome painting probes
      and triple colour painting by fluorescence in situ hybridization (FISH), we have
      analysed the frequency of chromosomal aberrations (CAs) involving chromosomes 1,
      4 and 10 in peripheral blood lymphocytes of 10 thyroid cancer patients sampled
      before and 1 week, 1 year and 3.5 years after therapeutic application of
      radioactive iodine in a self-controlled, longitudinal study. A highly significant
      3.4-fold increase in the frequency of chromosome breaks was observed 1 week after
      treatment with a similar representation of all chromosomes analysed. Although a
      significant decrease in dicentrics was observed during the first year after
      treatment, the frequency of chromosome aberrations remained over control levels
      until the last sampling time, 41-47 months post-treatment. The same behaviour, in
      terms of induction and persistence, was observed for all three chromosomes,
      confirming our previous results in vitro and rejecting the reported suggestion
      that chromosome 10 is radiosensitive in vivo. Our finding that the dynamics of
      radiation-induced CA in vivo is independent on the chromosome of choice suggests
      that this variable is not important in retrospective studies.

PMID- 10946250
TI  - A comparison of the in vitro genotoxicity of tri- and hexavalent chromium.
AB  - Chromium can be found in the environment in two main valence states: hexavalent
      (Cr(VI)) and trivalent (Cr(III)). Cr(VI) salts are well known human carcinogens,
      but the results from in vitro studies are often conflicting. Cr(VI) primarily
      enters the cells and undergoes metabolic reduction; however, the ultimate product
      of this reduction, Cr(III) predominates within the cell. In the present work, we
      compared the effects of tri- and hexavalent chromium on the DNA damage and repair
      in human lymphocytes using the alkaline single cell gel electrophoresis (comet
      assay). Potassium dichromate induced DNA damage in the lymphocytes, measured as
      the increase in comet tail moment. The effect was dose-dependent. Treated cells
      were able to recover within a 120-min incubation. Cr(III) caused greater DNA
      migration than Cr(VI). The lymphocytes did not show measurable DNA repair.
      Vitamin C at 50 microM reduced the extent of DNA migration. This was either due
      to a decrease in DNA strand breaks and/or alkali labile sites induced by Cr(VI)
      or to the formation of DNA crosslinks by Cr(VI) in the presence of vitamin C.
      Vitamin C, however, did not modify the effects of Cr(III). Catalase, an enzyme
      inactivating hydrogen peroxide, decreased the extent of DNA damage induced by
      Cr(VI) but not the one induced by Cr(III). Lymphocytes exposed to Cr(VI) and
      treated with endonuclease III, which recognizes oxidized pyrimidines, displayed
      greater extent of DNA damage than those not treated with the enzyme. Such an
      effect was not observed when Cr(III) was tested. The results obtained suggest
      that reactive oxygen species and hydrogen peroxide may be involved in the
      formation of DNA lesions by hexavalent chromium. The comet assay did not indicate
      the involvement of oxidative mechanisms in the DNA-damaging activity of trivalent
      chromium and we speculate that its binding to cellular ligands may play a role in
      its genotoxicity.

PMID- 10946252
TI  - Are baseline frequencies of SCEs, CAs, and MN in human lymphocytes related to
      hematological values?
AB  - In the present study, the correlation among several hematic values and the
      baseline frequencies of sister chromatid exchanges (SCEs), chromosome aberrations
      (CAs), and micronucleus (MN) were evaluated in human peripheral blood lymphocytes
      from a group of 1429 volunteers. Donors were selected to be representative of the
      general population of people living in the city of Pisa (Italy). By the use of
      the principal component analysis (PCA), principal components (PCs) were extracted
      from the complex pattern of correlations intrinsic in the hematic values (for
      example such as those among hemoglobin content, hematocrit, and erythrocyte
      count), and were tested for correlation on SCE, CA and MN frequencies. The seven
      PCs extracted (among 20 hematic values) were either positively or negatively
      correlated with the three cytogenetic endpoints. However, after correction by
      independent confounding factors (such as the age), with the use of the
      coefficient of partial correlation (CPC) analysis, only one PC significantly held
      the correlation with MN frequencies. This PC had the main contribution from the
      correlation between the concentration of potassium and the activity of alkaline
      phosphatase. These variables are known to be markers for bone (calcium)
      metabolism and are negatively correlated with MN frequencies. Because MN can
      arise from aneuploidy, the hematic concentrations of calcium may be important for
      stabilizing the mitotic process in stimulated lymphocytes. Finally, our study
      shows that the analysis of the hematic values adds very little information and
      removes a meaningless part of variance of the total variability observed for
      SCEs, CAs and MN.

PMID- 10946253
TI  - The T cell chemoattractant IFN-inducible protein 10 is essential in host defense
      against viral-induced neurologic disease.
AB  - The contribution of the T cell chemoattractant chemokine IFN-inducible protein 10
      (IP-10) in host defense following viral infection of the CNS was examined. IP-10
      is expressed by astrocytes during acute encephalomyelitis in mouse hepatitis
      virus-infected mice, and the majority of T lymphocytes infiltrating into the CNS
      expressed the IP-10 receptor CXCR3. Treatment of mice with anti-IP-10 antisera
      led to increased mortality and delayed viral clearance from the CNS as compared
      with control mice. Further, administration of anti-IP-10 led to a >70% reduction
      (p </= 0.001) in CD4+ and CD8+ T lymphocyte infiltration into the CNS, which
      correlated with decreased (p </= 0.01) levels of IFN-gamma. These data indicate
      that IP-10 functions as a sentinel molecule in host defense and is essential in
      the development of a protective Th1 response against viral infection of the CNS.

PMID- 10946254
TI  - CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death.
AB  - Galectin-1, an endogenous lectin expressed in lymphoid organs and immune
      privileged sites, induces death of human and murine thymocytes and T cells.
      Galectin-1 binds to several glycoproteins on the T cell surface, including CD7.
      However, the T cell surface glycoprotein receptors responsible for delivering the
      galectin-1 death signal have not been identified. We show that CD7 is required
      for galectin-1-mediated death. This demonstrates a novel function for CD7 as a
      death trigger and identifies galectin-1/CD7 as a new biologic death signaling
      pair.

PMID- 10946255
TI  - Outer membrane protein A (OmpA) binds to and activates human macrophages.
AB  - Outer membrane protein (Omp)A is highly represented and conserved in the
      Enterobacteriaceae family. Using a recombinant OmpA from Klebsiella pneumoniae
      (P40), we have analyzed the interaction between OmpA and macrophages. We report
      that Alexa488-labeled P40 binds (at 4 degrees C) to murine and human macrophages
      in a dose-dependent manner and is rapidly internalized (at 37 degrees C). No
      binding or internalization of the Alexa488-labeled glycophorin A control protein
      is observed under the same conditions. Furthermore, P40 up-regulates the
      production of IL-1beta, IL-8, IL-10, IL-12, and TNF-alpha by human macrophages
      and of NO by the RAW 264.7 murine macrophage cell line. P40 also synergizes with
      IFN-gamma and suboptimal concentrations of LPS to up-regulate the production of
      these mediators. In conclusion, P40 binds to and activates macrophages. These
      data suggest that recognition of OmpA by macrophages may be an initiating event
      in the antibacterial host response.

PMID- 10946257
TI  - Expression of human complement receptor 2 (CR2, CD21) in Cr2-/- mice restores
      humoral immune function.
AB  - Complement receptor type 2 (CR2, CD21) is expressed by both human and murine B
      cells and has been demonstrated to play a pivotal role in the humoral immune
      response. We have reconstituted Cr2-/- mice with an 80-kb human genomic fragment
      (designated P1-5) containing the full-length human CR2 (hCR2) gene. Transfection
      of P1-5 into the mouse A20 B cell line confirmed that it would direct expression
      of the hCR2 protein in mouse B cells. Immunoprecipitation analysis in these cells
      revealed that hCR2 coassociates with mouse CD19. After creation of transgenic
      mice using P1-5, we found significant expression of hCR2 on peripheral blood and
      splenic B cells by flow cytometric analysis. RT-PCR analysis of tissues and
      purified cell populations from transgene-positive mice revealed that hCR2
      expression was restricted to B cells and the spleen in a pattern that matches
      mouse CR2. To rigorously assess the functional capabilities of hCR2, the
      transgene was bred onto Cr2-/- mice, which have a notable defect in response to
      SRBC Ag. We found that Cr2-/- mice expressing hCR2 had a substantial restoration
      of the humoral immune response to SRBC as compared with nontransgenic Cr2-/-
      littermate controls. Overall, this study suggests that hCR2 is able to substitute
      for mouse CR2 in the murine immune system. Therefore, hCR2-transgenic mice offer
      a valuable model system to further examine immunologic roles as well as structure
      function relationships important for hCR2 function in primary cells in vivo.

PMID- 10946256
TI  - CD8+ T cells are necessary for recognition of allelic, but not locus-mismatched
      or xeno-, HLA class I transplantation antigens.
AB  - Although HLA transgenic mice (HLA TgM) could provide a powerful approach to
      investigate human MHC-specific T cell responsiveness, the extent to which these
      molecules are recognized by the mouse immune system remains unclear. We
      established TgM expressing HLA class I alleles A2, B7, or B27 in their fully
      native form (HLAnat) or as hybrid molecules (HLAhyb) of the HLA alpha1/alpha2
      domains linked to the H-2Kb alpha3, transmembrane, and cytoplasmic domains (i.e.,
      to maintain possible species-specific interactions). Comparison of each as xeno-
      (i.e., by non-TgM) vs allo- (i.e., by TgM carrying an alternate HLA allele)
      transplantation Ags revealed the following: 1) Although HLAhyb molecules induced
      stronger xeno-CD8+ T cell responses in vitro, additional effector mechanisms must
      be active in vivo because HLAnat skin grafts were rejected faster by non-TgM; 2)
      gene knockout recipients showed that xenorejection of HLAnat and, unexpectedly,
      HLAhyb grafts doesn't depend on CD8+ or CD4+ T cells or B cells; 3) each HLAhyb
      strain developed tolerance to "self" but rejected allele- (-B27 vs -B7) and locus
      (-B vs -A) mismatched grafts, the former requiring CD8+ T cells, the latter by
      CD8+ T cell-independent mechanisms. The finding that recognition of xeno-HLAhyb
      does not require CD8+ T cells while recognition of the identical molecule in a
      strictly allo context does, demonstrates an alpha1/alpha2 domain-dependent
      difference in effector mechanism(s). Furthermore, the CD8+ T cell-independence of
      locus-mismatched rejection suggests the degree of similarity between self and non
      self alpha1/alpha2 determines the effector mechanism(s) activated. The HLA Tg
      model provides a unique approach to characterize these mechanisms and develop
      tolerance protocols in the context of human transplantation Ags.

PMID- 10946258
TI  - Stat-1 is not essential for inhibition of B lymphopoiesis by type I IFNs.
AB  - Type I IFNs, IFN-alpha, -beta, and -omega, are cytokine family members with
      multiple immune response roles, including the promotion of cell growth and
      differentiation. Conversely, the type I IFNs are potent inhibitors of IL-7
      dependent growth of early B lineage progenitors, effectively aborting further B
      lineage differentiation at the pro-B cell stage. Type I IFNs alpha and beta
      function via receptor-mediated activation of a Jak/Stat signaling pathway in
      which Stat-1 is functionally important, because many IFN-induced responses are
      abrogated in Stat-1-deficient mice. To the contrary, we show here that the
      inhibition of IL-7-dependent B lymphopoiesis by IFN-alphabeta is unaffected in
      Stat-1-deficient mice. The present data indicate that the type I IFNs can
      activate an alternative signaling pathway in which neither Stat-1 nor
      phosphatidylinositol 3'-kinase are essential components.

PMID- 10946259
TI  - Age-related dysregulation in CD8 T cell homeostasis: kinetics of a diversity
      loss.
AB  - Relative diversity and representation of peripheral T cells bearing different TCR
      Vbeta families are remarkably tightly regulated between birth and advanced
      adulthood. By contrast, individual elderly humans and C3H.SW and B10.BR aged mice
      display drastic disruption in such regulation. It was suggested that the
      alterations in the murine aged T cell compartment were due to age-related clonal
      T cell expansions (TCE). Here, we studied the kinetics of homeostatic
      dysregulation of T cell populations in aged C57BL/6 (B6) mice. Using mAb
      staining, we show that the percentages of alphabeta+CD8+ or CD4+ T cells bearing
      different TCRVbeta elements remain virtually constant in mice up to 12 mo of age.
      In 22-mo-old mice, however, there is a dramatic disturbance of this pattern owing
      to the emergence of CD8+ TCE. Expanded T cells did not show any obvious bias in
      Vbeta usage and were derived in all cases examined thus far from a single clone.
      TCE appeared later in life, compared with B cell clonal expansions. However, and
      in contrast to those detected in humans, TCE were frequently unstable
      disappearing within 2-4 mo, with other TCE appearing within the same time frame.
      Additional studies carried on thymic T cells, thymectomized mice, and young T
      transferred cells into Rag1-/- mice suggest that the clonal expansions occur in
      the periphery and that their onset is accelerated by decreased thymic output
      and/or function(s).

PMID- 10946260
TI  - Mycophenolate mofetil impairs the maturation and function of murine dendritic
      cells.
AB  - The immunosuppressive drug, mycophenolate mofetil (MMF), has been successfully
      introduced in allogeneic transplantation medicine and, more recently, in the
      treatment of autoimmune skin disorders. MMF inhibits lymphocyte proliferation via
      a blockade of the enzyme inosine 5'-monophosphate dehydrogenase, an enzyme on
      which lymphocytes solely depend to generate the purines necessary for DNA/RNA
      synthesis. To investigate the effects of MMF on cutaneous immune responses, a
      murine model of contact hypersensitivity (CHS) was used, with oxazolone or
      trinitrochlorobenzene as a contact allergen. Compared with the respective
      vehicle, i.p. applied MMF significantly inhibited the elicitation and,
      surprisingly, the induction of CHS responses. This prompted further studies into
      the effects of MMF on Ag presentation. Bone marrow-derived dendritic cells (DC)
      were cultured with GM-CSF and IL-4 in the presence of MMF and were tested for
      their Ag-presenting capacity. Sensitization and elicitation of CHS and delayed
      type hypersensitivity responses by s. c. injected haptenated DC were reduced upon
      preincubation of DC with MMF. CHS responses were not impaired upon
      resensitization, indicating that MMF does not induce hapten-specific
      immunotolerance. In addition, MMF decreased the ability of DC to stimulate
      allogeneic T cells in MLR assays. Accordingly, flow cytometric analyses revealed
      a dose-dependent reduction of the expression of CD40, CD80, CD86, I-A, and ICAM-1
      on DC with a concurrent reduction of IL-12 production. These data suggest that
      MMF, in addition to affecting T lymphocytes, directly affects APC, resulting in
      an impairment of immune responses. They furthermore point to a possible role of
      inosine 5'-monophosphate dehydrogenase in the maturation of DC.

PMID- 10946262
TI  - Stress renders T cell blasts sensitive to killing by activated syngeneic NK
      cells.
AB  - Exposure of primary T cell blasts to stress in the forms of heat, hydrogen
      peroxide, or high-density growth conditions resulted in a state of enhanced
      susceptibility to killing by syngeneic IL-2-activated NK cells or lymphokine
      activated killer cells, but not to killing by CTL. Cytotoxicity was perforin
      mediated and was not due to decreased target expression of total MHC class I. The
      levels of stress used had little effect on cell viability. For thermal stress,
      sensitization increased with temperature, required a minimum exposure time, and
      disappeared when cells were given a long enough recovery time. Our data support a
      model that predicts that activated NK cells play a role in the immunosurveillance
      of nontransformed stressed cells in normal animals.

PMID- 10946261
TI  - IL-3 increases production of B lymphoid progenitors from human CD34+CD38- cells.
AB  - The effect of IL-3 on the B lymphoid potential of human hemopoietic stem cells is
      controversial. Murine studies suggest that B cell differentiation from
      uncommitted progenitors is completely prevented after short-term exposure to IL
      3. We studied B lymphopoiesis after IL-3 stimulation of uncommitted human
      CD34+CD38- cells, using the stromal cell line S17 to assay the B lymphoid
      potential of stimulated cells. In contrast to the murine studies, production of
      CD19+ B cells from human CD34+CD38- cells was significantly increased by a 3-day
      exposure to IL-3 (p < 0.001). IL-3, however, did not increase B lymphopoiesis
      from more mature progenitors (CD34+CD38+ cells) or from committed CD34-CD19+ B
      cells. B cell production was increased whether CD34+CD38- cells were stimulated
      with IL-3 during cocultivation on S17 stroma, on fibronectin, or in suspension.
      IL-3Ralpha expression was studied in CD34+ populations by RT-PCR and FACS. High
      IL-3Ralpha protein expression was largely restricted to myeloid progenitors.
      CD34+CD38- cells had low to undetectable levels of IL-3Ralpha by FACS. IL-3
      responsive B lymphopoiesis was specifically found in CD34+ cells with low or
      undetectable IL-3Ralpha protein expression. IL-3 acted directly on progenitor
      cells; single cell analysis showed that short-term exposure of CD34+CD38- cells
      to IL-3 increased the subsequent cloning efficiency of B lymphoid and B
      lymphomyeloid progenitors. We conclude that short-term exposure to IL-3
      significantly increases human B cell production by inducing proliferation and/or
      maintaining the survival of primitive human progenitors with B lymphoid
      potential.

PMID- 10946263
TI  - Antibody production in mice deficient for complement receptors 1 and 2 can be
      induced by IgG/Ag and IgE/Ag, but not IgM/Ag complexes.
AB  - Deficiencies in C factors C2, C3, or C4 as well as lack of C receptors 1 and 2
      (CR1/2) lead to impaired Ab production. Classical pathway activation plays a
      major role, as mice deficient in factor B, a key factor in the alternative
      pathway, have normal Ab production. Abs in complex with their specific Ag are
      known to feedback regulate the Ab response, and enhanced responses are initiated
      by IgM, IgE, and IgG. IgM acts via the C system, whereas IgE and IgG can operate
      independently of C via Fc receptors. Here we have investigated whether these
      isotypes are able to enhance Ab responses in mice lacking CR1/2. SRBC-specific
      IgM, administered with SRBC, does not enhance Ab responses in these animals. In
      contrast, 2,4, 6-trinitrophenyl-specific IgE and IgG2a, administered with BSA
      2,4, 6-trinitrophenyl, induce potent Ab responses in CR1/2-deficient mice.
      Additionally, BSA administered with CFA or alum induced strong Ab responses in
      the absence of CR1/2. These results indicate that CR1/2 is needed to promote IgM
      mediated induction of primary Ab responses. The data also show that the need for
      CR1/2 can be circumvented by Abs typical of a secondary immune response forming
      complexes with Ag or by conventional adjuvants, presumably mimicking
      physiological inflammatory reactions.

PMID- 10946264
TI  - Contemporary analysis of MHC-related immunodominance hierarchies in the CD8+ T
      cell response to influenza A viruses.
AB  - Early studies of influenza virus-specific CD8+ T cell-mediated immunity indicated
      that the level of CTL activity associated with H2Db is greatly diminished in mice
      that also express H2Kk. Such MHC-related immunodominance hierarchies are of some
      interest, as they could lead to variable outcomes for peptide-based vaccination
      protocols in human populations. The influence of H2Kk on the H2Db-restricted
      response profile has thus been looked at again using a contemporary,
      quantitative, IFN-gamma-based flow cytometric assay. The depressive effect of
      H2Kk was very apparent for the influenza DbPA224 epitope and was also reproduced
      when CTL activity was measured for H2Db-expressing targets pulsed with the
      immunodominant NP366 peptide. The secondary CD8+IFN-gamma+ DbNP366-specific
      response was much greater in parental H2b than in H2kxbF1 mice, but the sizes of
      the CD8+ sets specific for KkNP50 and DbNP366 were essentially equivalent in the
      F1 animals. Thus, although the immunodominance profile associated with DbNP366 is
      lost when H2Kk is also present, the response is still substantial. A further, MHC
      related effect was also identified for the KkNS1152 epitope, which was
      consistently associated with a greater CD8+IFN-gamma+ response in H2KkDb
      recombinant than in (H2KkDk x H2KbDb)F1 mice. The diminished DbPA224 response in
      H2kxbF1 mice was characterized by loss of a prominent Vbeta7 TCR responder
      phenotype, supporting the idea that TCR deletion during ontogeny shapes the
      available repertoire. The overall conclusion is that these MHC-related
      immunodominance hierarchies are more subtle than the early CTL assays suggested
      and, although inherently unpredictable, are unlikely to cause a problem for
      peptide-based vaccine strategies.

PMID- 10946265
TI  - An essential role for the IL-7 receptor during intrathymic expansion of the
      positively selected neonatal T cell repertoire.
AB  - Intrathymic T cell development is a multistage process involving discrete phases
      of proliferation as well as differentiation. From studies on IL-7 or IL-7Ralpha
      deficient mice, it is clear that the IL-7 receptor (IL-7R) plays a critical role
      during the initial stages of intrathymic CD4-8- precursor development. In
      contrast, the role of IL-7R in later stages of thymocyte development are unclear.
      Here, we have used various approaches to investigate directly the role of the IL
      7R in thymocyte positive selection and the recently described phase of
      postselection proliferation. First, we show that positive selection involves
      selective up-regulation of IL-7Ralpha- and IL-7Rgamma-chains, with the majority
      of CD4+ and CD8+ cells being IL-7R+. Second, MHC class II+ thymic epithelium
      which drives postselection proliferation-expresses IL-7 mRNA. Finally, analysis
      of positive selection and postselection proliferation in thymocytes from IL
      7Ralpha-/- neonates shows that positive selection occurs normally, whereas
      postselection expansion is drastically reduced. Thus, our data provide the first
      evidence that, as well as playing a role during early phases of thymic
      development, IL-7R mediates intrathymic expansion of positively selected
      thymocytes, which may aid in establishment of the neonatal peripheral T cell
      pool.

PMID- 10946266
TI  - Break of T cell ignorance to a viral antigen in the liver induces hepatitis.
AB  - To study peripheral tolerance of CD8 T cells to a classically MHC-restricted
      peptide Ag expressed in hepatocytes, ALB1 transgenic (tg) mice expressing the CTL
      epitope GP33 of the lymphocytic choriomeningitis virus glycoprotein under control
      of the mouse albumin promoter were generated. ALB1 mice exclusively expressed the
      GP33 transgene in the liver and, at a 100- to 1000-fold lower level, in the
      thymus. TCR-tg mice specific for the GP33 epitope were used to directly follow
      GP33-specific T cells in vivo. These experiments revealed that 1) thymic
      expression of the GP33 transgene led to incomplete central deletion of TCR-tg
      cells; and 2) peripheral TCR-tg cells in ALB1 mice ignored the GP33 transgene
      expressed in hepatocytes. Ignorance of adoptively transferred TCR-tg cells in
      ALB1 mice was broken by infection with lymphocytic choriomeningitis virus,
      leading to induction of hepatitis in ALB1, but not in control, mice. Taken
      together, we have established a novel model of virus-induced CD8 T cell-mediated
      autoimmune hepatitis in mice and demonstrate that naive CD8 T cells may ignore
      Ags expressed in the liver.

PMID- 10946267
TI  - Activation via multiple signaling pathways induces down-regulation of platelet
      activating factor receptors on human B lymphocytes.
AB  - Platelet-activating factor receptor (PAFR) has been identified in B cell lines
      and primary human B cells, but the regulation of PAFR during B cell activation
      has not been completely elucidated. In the present study, we have investigated
      the effects of B cell activation on PAFR binding parameters, PAFR mRNA and PAF
      triggered intracellular calcium mobilization. The human B lymphoid cell line
      LA350 was shown to exhibit high levels of PAFR (48,550 +/- 4,310 sites/cell) as
      determined by radio-ligand binding assay with PAFR antagonist [3H]WEB2086.
      Treatment with phorbol 12,13-dibutyrate caused a biphasic reduction of PAFR
      binding. The early phase was inhibited by the protein kinase C inhibitor
      bisindolylmaleimide I (BIM), whereas the late phase was not blocked by BIM,
      protein tyrosine kinase inhibitor genistein, or the mitogen-activated protein
      kinase/extracellular signal-related kinase inhibitor PD98059. However,
      staurosporine, a broad-spectrum protein kinase inhibitor, completely inhibited
      the late phase down-regulation. Ionomycin also decreased [3H]WEB2086 binding
      sites, whereas the combination of PDB and ionomycin induced a greater reduction
      than either agent alone. Cross-linking of B cell receptor by anti-IgM Ab also
      induced down-regulation of PAFR, which was abolished by genistein or PD98059, but
      not by BIM or staurosporine. The decrease in surface PAFR number was closely
      paralleled by the reduction in PAFR mRNA both in LA350 cells and human tonsillar
      B cells, and was associated with decreased response to PAF indicated by decreased
      intracellular calcium mobilization. These data show that multiple signaling
      pathways are involved in down-regulating PAFR expression during B cell activation
      and development.

PMID- 10946268
TI  - T cell effector function and anergy avoidance are quantitatively linked to cell
      division.
AB  - We have shown previously that T cells activated by optimal TCR and CD28 ligation
      exhibit marked proliferative heterogeneity, and approximately 40% of these
      activated cells fail entirely to participate in clonal expansion. To address how
      prior cell division influences the subsequent function of primary T cells at the
      single cell level, primary CD4+ T cells were subjected to polyclonal stimulation,
      sorted based on the number of cell divisions they had undergone, and restimulated
      by ligation of TCR/CD28. We find that individual CD4+ T cells exhibit distinct
      secondary response patterns that depend upon their prior division history, such
      that cells that undergo more rounds of division show incrementally greater IL-2
      production and proliferation in response to restimulation. CD4+ T cells that fail
      to divide after activation exist in a profoundly hyporesponsive state that is
      refractory to both TCR/CD28-mediated and IL-2R-mediated proliferative signals. We
      find that this anergic state is associated with defects in both TCR-coupled
      activation of the p42/44 mitogen-activated protein kinase (extracellular signal
      related kinase 1/2) and IL-2-mediated down-regulation of the cell cycle inhibitor
      p27kip1. However, these defects are selective, as TCR-mediated intracellular
      calcium flux and IL-2R-coupled STAT5 activation remain intact in these cells.
      Therefore, the process of cell division or cell cycle progression plays an
      integral role in anergy avoidance in primary T cells, and may represent a driving
      force in the formation of the effector/memory T cell pool.

PMID- 10946269
TI  - Early growth response (Egr)-1 gene induction in the thymus in response to TCR
      ligation during early steps in positive selection is not required for CD8 lineage
      commitment.
AB  - The early growth response gene 1 (Egr-1) is induced during positive selection in
      the thymus and has been implicated in the differentiation of CD4+ thymocytes.
      Here, we show that signals that specifically direct CD8 lineage commitment also
      induce Egr-1 DNA-binding activity in the nucleus. However, we find that
      pharmacological inhibition of mitogen-activated protein kinase/extracellular
      signal-related kinase kinase activity potently inhibits Egr-1 DNA-binding
      function at concentrations that promote differentiation of CD8+ thymocytes,
      suggesting Egr-1 activity is not essential for CD8 commitment. To further
      determine the role of Egr-1 in thymocyte development, we compare steady-state Egr
      1 DNA-binding activity in thymocytes from mice with defined defects in positive
      selection. The data indicate that the appearance of functional Egr-1 is
      downstream of signals induced by TCR/MHC engagement, whereas it is less sensitive
      to alterations in Lck-mediated signals, and does not correlate directly with
      proficient positive selection. Egr-1 is one of the earliest transcription factors
      induced upon TCR ligation on immature thymocytes, and plays a potential role in
      the transcription of genes involved in thymocyte selection.

PMID- 10946270
TI  - Selective inhibition of IgG-mediated phagocytosis in gelsolin-deficient murine
      neutrophils.
AB  - Phagocytosis and the microbicidal functions of neutrophils require dynamic
      changes of the actin cytoskeleton. We have investigated the role of gelsolin, a
      calcium-dependent actin severing and capping protein, in peripheral blood
      neutrophils from gelsolin-null (Gsn-) mice. The phagocytosis of complement
      opsonized yeast was only minimally affected. In contrast, phagocytosis of IgG
      opsonized yeast was reduced close to background level in Gsn- neutrophils. Thus,
      gelsolin is essential for efficient IgG- but not complement-mediated
      phagocytosis. Furthermore, attachment of IgG-opsonized yeast to Gsn- neutrophils
      was reduced ( approximately 50%) but not to the same extent as ingestion (
      approximately 73%). This was not due to reduced surface expression of the Fcgamma
      receptor or its lateral mobility. This suggests that attachment and ingestion of
      IgG-opsonized yeast by murine neutrophils are actin-dependent and gelsolin is
      important for both steps in phagocytosis. We also investigated granule exocytosis
      and several steps in phagosome processing, namely the formation of actin around
      the phagosome, translocation of granules, and activation of the NADPH-oxidase.
      All these functions were normal in Gsn- neutrophils. Thus, the role of gelsolin
      is specific for IgG-mediated phagocytosis. Our data suggest that gelsolin is part
      of the molecular machinery that distinguishes complement and IgG-mediated
      phagocytosis. The latter requires a more dynamic reorganization of the
      cytoskeleton.

PMID- 10946271
TI  - Survival and homeostatic proliferation of naive peripheral CD4+ T cells in the
      absence of self peptide:MHC complexes.
AB  - TCR-self peptide:MHC interactions play a critical role in thymic positive
      selection, yet relatively little is known of their function in the periphery. It
      has been suggested that continued contact with selecting MHC molecules is
      necessary for long-term peripheral maintenance of naive T cells. More recent
      studies have also demonstrated a role for specific self peptide:MHC complexes in
      the homeostatic expansion of naive T cells in lymphopenic mice. Our examination
      of these processes revealed that, whereas self class II MHC molecules do have a
      modest effect on long-term survival of individual CD4+ T cells, interactions with
      specific TCR ligands are not required for peripheral naive CD4+ T cell
      maintenance. In contrast, selective engagement of TCRs by self-peptide:MHC
      complexes does promote proliferation of CD4+ T cells under severe lymphopenic
      conditions, and this division is associated with an activation marker phenotype
      that is different from that induced by antigenic stimulation. Importantly,
      however, the ability of naive T cells to divide in response to homeostatic
      stimuli does not appear to be stringently dependent on TCR-self peptide:MHC
      interactions. Therefore, these results show that the factors regulating survival
      and homeostatic expansion of naive T cells in the periphery are not identical. In
      addition, we provide evidence for a novel form of T cell proliferation that can
      occur independently of TCR signaling and suggest that this reflects another
      mechanism regulating homeostatic T cell expansion.

PMID- 10946273
TI  - B lymphocyte-derived IL-16 attracts dendritic cells and Th cells.
AB  - Interaction of B lymphocytes with Th cells is a fundamental step in the
      establishment of humoral immunity, and recent evidence suggests that direct
      interaction between B lymphocytes and dendritic cells (DCs) is also an important
      prerequisite. Factors involved in the selective recruitment of Th cells and DCs
      by B lymphocytes are insufficiently defined. We set out to delineate the role of
      IL-16, the soluble ligand of CD4, which is expressed on Th cells and DCs. B
      lymphocytes express IL-16 mRNA and synthesize bioactive IL-16 protein, and IL-16
      is expressed in lymph node follicles in situ. B lymphocyte supernatant
      efficiently induces migration of CD4+ Th cells, monocyte-derived DCs, and
      circulating blood DCs in nitrocellulose filter-based assays. Neutralization of IL
      16 bioactivity strongly inhibits this migratory response, suggesting that IL-16
      might be a major chemotactic factor derived from B cells. The present data
      further support the idea that IL-16 might have a role in the initiation of
      cellular as well as humoral immunity by mediating the cellular cross-talk among T
      lymphocytes, B cells, and DCs, leading to recruitment of these cell types at
      common anatomical sites.

PMID- 10946272
TI  - Selective malformation of the splenic white pulp border in L1-deficient mice.
AB  - Lymphocytes enter the splenic white pulp by crossing the poorly characterized
      boundary of the marginal sinus. In this study, we describe the importance of L1,
      an adhesion molecule of the Ig superfamily, for marginal sinus integrity. We find
      that germline insertional mutation of L1 is associated with a selective
      malformation of the splenic marginal sinus. Other splenic structures remain
      intact. Immunofluorescence analysis of the extracellular framework of the spleen,
      using an Ab to laminin, reveals that L1 knockout mice have an irregularly shaped,
      discontinuous white pulp margin. Electron microscopic analysis shows that it is
      associated with bizarrely shaped marginal sinus lining cells at the periphery of
      the white pulp. These abnormalities correlate with the localization of L1 in
      normal mice in that L1 is normally expressed on marginal sinus lining cells at
      the white pulp border. These L1-immunopositive lining cells coexpress high levels
      of mucosal addressin cell adhesion molecule-1 and vimentin, indicating that they
      are of fibroblastic lineage and express a well-characterized addressin. Our
      findings are the first to implicate L1 in splenic lymphoid architectural
      development. Moreover, these findings help define the poorly characterized
      sinusoidal boundary across which mononuclear cells cross to enter the splenic
      white pulp.

PMID- 10946274
TI  - Evidence for two subgroups of CD4-CD8- NKT cells with distinct TCR alpha beta
      repertoires and differential distribution in lymphoid tissues.
AB  - NKT cells are a subset of T lymphocytes that is mainly restricted by the
      nonclassical MHC class I molecule, CD1d, and that includes several
      subpopulations, in particular CD4+ and CD4-CD8- (DN) cells. In the mouse,
      differential distribution of these subpopulations as well as heterogeneity in the
      expression of various markers as a function of tissue localization have been
      reported. We have thus undertaken a detailed study of the DN NKT cell
      subpopulation. With a highly sensitive semiquantitative RT-PCR technique, its TCR
      repertoire was characterized in various tissues. We found that mouse DN NKT cells
      are a variable mixture of two subgroups, one bearing the invariant Valpha14 chain
      paired to rearranged Vbeta2, Vbeta7, Vbeta8.1, Vbeta8.2, or Vbeta8.3 beta-chains
      and the other exhibiting unskewed alpha- and beta-chains. The proportion of these
      subgroups varies from about 100:0 in thymus, 80:20 in liver, and 50:50 in spleen
      to 20:80% in bone marrow, respectively. Finally, further heterogeneity in the
      tissue-derived DN NKT cells was discovered by sequencing extensively Vbeta8.2
      Jbeta2.5 rearrangements in individual mice. Despite a few recurrences in TCR
      sequences, we found that each population exhibits its own and broad TCRbeta
      diversity.

PMID- 10946275
TI  - Binding kinetics, structure-activity relationship, and biotransformation of the
      complement inhibitor compstatin.
AB  - We have previously identified a 13-residue cyclic peptide, Compstatin, that binds
      to complement component C3 and inhibits complement activation. Herein, we
      describe the binding kinetics, structure-activity relationship, and
      biotransformation of Compstatin. Biomolecular interaction analysis using surface
      plasmon resonance showed that Compstatin bound to native C3 and its fragments C3b
      and C3c, but not C3d. While binding of Compstatin to native C3 was biphasic,
      binding to C3b and C3c followed the 1:1 Langmuir binding model; the affinities of
      Compstatin for C3b and C3c were 22- and 74-fold lower, respectively, than that of
      native C3. Analysis of Compstatin analogs synthesized for structure-function
      studies indicated that 1) the 11-membered ring between disulfide-linked Cys2
      Cys12 constitutes a minimal structure required for optimal activity; 2) retro
      inverso isomerization results in loss of inhibitory activity; and 3) some
      residues of the type I beta-turn segment also interact with C3. In vitro studies
      of Compstatin in human blood indicated that a major pathway of biotransformation
      was the removal of Ile1, which could be blocked by N-acetylation of the peptide.
      These findings indicate that acetylated Compstatin is stable against enzymatic
      degradation and that the type I beta-turn segment is not only critical for
      preservation of the conformational stability, but also involved in intermolecular
      recognition.

PMID- 10946277
TI  - MHC class II transactivator inhibits IL-4 gene transcription by competing with NF
      AT to bind the coactivator CREB binding protein (CBP)/p300.
AB  - The MHC class II transactivator (CIITA) activates the expression of multiple
      genes involved in Ag presentation, but inhibits Th2-type cytokine production,
      including IL-4, during Th1 cell differentiation. Th1 cells derived from CIITA
      deficient mice produce both Th1- and Th2-type cytokines, and the introduction of
      CIITA to Th2 cells down-regulates Th2-type cytokine gene transcription. Here we
      show that the IL-4 promoter is regulated by multiple protein-protein interactions
      among CIITA, NF-AT, and coactivator CBP/p300. The introduction of CBP/p300 and NF
      AT enhances the IL-4 promoter activity, and this activation was repressed by
      CIITA. Furthermore, our data show that CIITA competes with NF-AT to bind CBP/p300
      and that this competition dramatically influences transcriptional activation of
      the IL-4 promoter. We identified two domains of CIITA that interact with two
      distinct domains of CBP/p300 that are also recognized by NF-AT. CIITA mutants
      that retain the ability to interact with CBP/p300 are sufficient to inhibit NF-AT
      mediated IL-4 gene expression.

PMID- 10946276
TI  - Apoptosis induced by TGF-beta 1 in Burkitt's lymphoma cells is caspase 8
      dependent but is death receptor independent.
AB  - TGF-beta is a potent inducer of apoptosis in many Burkitt's lymphoma (BL) cell
      lines. In this study, we characterize this apoptotic process in the EBV-negative
      BL41 cell line. Induction of apoptosis was detected as early as 8 h after TGF
      beta treatment, as assayed by TUNEL and poly(ADP-ribose) polymerase cleavage.
      FACS analysis demonstrates that this proceeds predominately from the G1, but also
      from the G2/M phases of the cell cycle. We observed no early detectable changes
      in the steady-state levels of Bcl-2 and several of its family members after TGF
      beta treatment. We detected cleavage of caspases 2, 3, 7, 8, and 9 into their
      active subunits. Consistent with the involvement of these enzymes in TGF-beta
      mediated apoptosis, the broad spectrum caspase inhibitor benzyloxycarbonyl-Val
      Ala-Asp(Ome)-flouromethylketone (ZVAD-fmk) blocked TGF-beta-induced apoptosis and
      revealed a G1 arrest in treated cells. Use of specific caspase inhibitors
      revealed that the induction of apoptosis is caspase 8 dependent, but caspase 3
      independent. Activation of caspase 8 has been shown to be a critical event in
      death receptor-mediated apoptosis. However, TGF-beta treatment of BL41 cells was
      found not to affect the cell surface expression of Fas, TNF-R1, DR3, DR4, or DR5,
      or the steady-state expression levels of Fas ligand, TNF-R1, DR3, DR4, and DR5.
      Furthermore, blocking experiments indicated that TGF-beta-mediated apoptosis is
      not dependent on Fas ligand, TNF-alpha, tumor necrosis-like apoptosis-inducing
      ligand, or TNF-like weak inducer of apoptosis signaling. Therefore, it appears
      that TGF-beta induces apoptosis in BL cell lines via caspase 8 in a death
      receptor-independent fashion.

PMID- 10946278
TI  - Two clusters of acidic amino acids near the NH2 terminus of complement component
      C4 alpha'-chain are important for C2 binding.
AB  - Previous work has indicated a role for the NH2-terminal segment of the C3 alpha'
      chain in the binding interactions of C3b with a number of its protein ligands. In
      particular, we have identified two clusters of acidic residues, namely, E736 and
      E737 and to a lesser extent D730 and E731, as being important in the binding of
      C3b to factor B and complement receptor 1 and the binding of iC3b to complement
      receptor 3. Whereas human C3 and C4 have an overall sequence identity of 29%,
      over a segment near the NH2 termini of their respective alpha'-chains the
      sequence identity is 56% (70% chemical similarity). Given the functional
      similarity between the C4b-C2 and C3b-B interactions in the respective formation
      of the classical and alternative pathway C3 convertases, as well as the sequence
      conservation of two acidic clusters, we hypothesized that residues 744EED and
      749DEDD within the NH2-terminal segment of the C4 alpha'-chain would mediate in
      part the binding of C2 to C4b. We tested this hypothesis using three independent
      approaches. Site-directed mutagenesis experiments revealed that replacing subsets
      of the charged residues by their isosteric amides within either acidic cluster
      resulted in molecules having reduced C2 binding activity. Moreover, a synthetic
      peptide (C4 residues 740-756) encompassing the two acidic clusters was a specific
      inhibitor of the binding of C2 to red cell-associated C4b. Finally, Ab raised
      against the above peptide was able to block the interaction between red cell
      associated C4b and fluid phase C2. Taken together, these results strongly suggest
      that the NH2-terminal acidic residue-rich segment of C4 alpha'-chain contributes
      importantly to the interaction of C4b with C2.

PMID- 10946279
TI  - Identification and functional characterization of a new gene encoding the mouse
      terminal complement inhibitor CD59.
AB  - CD59 is a 18- to 20-kDa, GPI-anchored membrane protein that functions as a key
      regulator of the terminal step of the complement activation cascade. It restricts
      binding of C9 to the C5b-8 complex, thereby preventing the formation of the
      membrane attack complex (C5b-9 of complement). A single human CD59 gene has been
      identified, and corresponding genetic homologues from rat, mouse, and pig have
      been characterized in previous studies. In this study, we report the discovery
      and functional characterization of a separate cd59 gene in the mouse (referred to
      as cd59b, the previously characterized mouse cd59 gene as cd59a). Mouse cd59b is
      85% and 63% identical to cd59a at the nucleotide and amino acid level,
      respectively. In cDNA transfection experiments with Chinese hamster ovary cells,
      peptide-tagged cd59b was detected on the cell surface by flow cytometry and was
      shown to be susceptible to phosphatidylinositol-specific phospholipase C
      cleavage. Chinese hamster ovary cells expressing cd59b were significantly more
      resistant than control cells to human and mouse complement-mediated lysis. These
      results suggest that cd59b encodes a GPI-anchored protein that is functionally
      active as a membrane attack complex inhibitor. Northern blot analysis revealed
      that cd59b is expressed selectively in the mouse testis. In contrast, the major
      transcript of cd59a was shown to be expressed at high levels in the heart,
      kidney, liver, and lung, but only minimally in the testis. These results revealed
      the existence of two distinct cd59 genes in the mouse that are differentially
      regulated and that may have nonoverlapping physiological functions in vivo.

PMID- 10946280
TI  - Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M:
      structural receptor requirements for signal attenuation.
AB  - Stimulation of the IL-6R complex leads to Src homology domain containing tyrosine
      phosphatase 2 (SHP2) recruitment to the receptor subunit gp130 and its subsequent
      tyrosine phosphorylation. SHP2 is a two-SH2 domain-containing protein tyrosine
      phosphatase that is activated by many cytokines and growth factors. SHP2
      counteracts the activation of transcription factors of the STAT family and the
      induction of IL-6-responsive genes. Tyrosine 759 of gp130, the signal transducing
      subunit of the IL-6R complex, is essential for the phosphorylation of SHP2.
      Mutation of tyrosine 759 to phenylalanine leads to an enhanced inducibility of IL
      6-dependent genes. Here we demonstrate that no further tyrosines in the
      cytoplasmic part of gp130 are required for the phosphorylation of SHP2. We also
      tested whether the tyrosine 759 motifs in both subunits of the gp130 dimer are
      required for SHP2 association and tyrosine phosphorylation. Interestingly, one
      SHP2-recruiting phosphotyrosine motif in a single chain of the gp130 dimer is
      sufficient to mediate SHP2 association to the gp130 receptor subunit and its
      tyrosine phosphorylation as well as to attenuate IL-6-dependent gene induction.
      Furthermore, we show that repression of gene induction via Y759 does not require
      the presence of the SHP2 and STAT recruitment sites within the same receptor
      subunit, but within the same receptor complex. The Y759 motif in gp130 also
      attenuates gene induction mediated by the oncostatin M and leukemia inhibitory
      factor receptor complexes, which both contain gp130 as the shared subunit.

PMID- 10946282
TI  - Efficient internalization of IL-2 depends on the distal portion of the
      cytoplasmic tail of the IL-2R common gamma-chain and a lymphoid cell environment.
AB  - The common gamma-chain (gammac), a subunit of the IL-2R, is essential for high
      affinity ligand binding and signal transduction due to Jak3 association to
      gammac. Another consequence of IL-2/IL-2R interaction is rapid receptor-mediated
      endocytosis of the receptor-ligand complex. In the present study, we establish
      that this rapid endocytosis of IL-2 in a T cell tumor line is dependent upon the
      cytoplasmic tail of gammac. Deletion mutants of the cytoplasmic tail mapped this
      activity to 9 aa of gammac, 45-54 aa distal to the transmembrane region. In
      contrast, ligand-independent constitutive endocytosis of gammac occurred more
      slowly and was dependent upon a PEST sequence in a more membrane-proximal region
      of the cytoplasmic tail of gammac. Thus, this receptor subunit may use distinct
      sorting signals for its constitutive regulation and ligand-induced endocytosis.
      Rapid endocytosis of IL-2 was inhibited by the tyrosine kinase inhibitor
      genistein, implicating a role for a signal transduction pathway in IL-2
      internalization. However, one T cell line bearing a mutant gammac exhibited
      impaired endocytosis of IL-2, despite normal IL-2-induced Jak/STAT activation.
      Furthermore, inefficient endocytosis of IL-2 was noted after transfection of the
      COS7 epithelial cell line with the IL-2R, and further reconstitution of these
      cells with Jak/STAT proteins did not enhance this internalization. Collectively,
      these latter findings indicate that rapid endocytosis of IL-2 is dependent upon
      cellular signaling in lymphoid cell environment that is not solely a consequence
      of the presence of the Jak/STAT pathway.

PMID- 10946281
TI  - The IgA/IgM receptor expressed on a murine B cell lymphoma is poly-Ig receptor.
AB  - T560, a mouse B lymphoma that originated in gut-associated lymphoid tissue,
      expresses receptors that bind dimeric IgA and IgM in a mutually inhibitory manner
      but have little affinity for monomeric IgA. Evidence presented in this paper
      indicates that the receptor is poly-Ig receptor (pIgR) known in humans and
      domestic cattle to bind both IgA and IgM. The evidence includes the demonstration
      that binding of IgM is J chain dependent, and that pIg-precipitated receptor has
      an appropriate Mr of 116-120 kDa and can be detected on immunoblots with specific
      rabbit anti-mouse pIgR. Overlapping RT-PCR performed using template mRNA from
      T560 cells and oligonucleotide primer pairs designed from the published sequence
      of mouse liver pIgR indicate that T560 cells express mRNA virtually identical
      with that of the epithelial cell pIgR throughout its external, transmembrane, and
      intracytoplasmic coding regions. Studies using mutant IgAs suggest that the
      Calpha2 domain of dimeric IgA is not involved in high-affinity binding to the
      T560 pIgR. Inasmuch as this mouse B cell pIgR binds IgM better than IgA, it is
      similar to human pIgR and differs from rat, mouse, and rabbit epithelial cell
      pIgRs that bind IgA but not IgM. Possible explanations for this difference are
      discussed. All clones of T560 contain some cells that spontaneously secrete both
      IgG2a and IgA, but all of the IgA recoverable from the medium and from cell
      lysates is monomeric; it cannot be converted to secretory IgA by T560 cells.

PMID- 10946283
TI  - Pigs express multiple forms of decay-accelerating factor (CD55), all of which
      contain only three short consensus repeats.
AB  - We report the cloning of cDNAs encoding multiple isoforms of the pig analogue of
      human decay-accelerating factor (DAF; CD55). Screening of a pig muscle cDNA
      library using a human DAF probe identified a single clone that encoded a DAF-like
      molecule comprising three short consensus repeats (SCR) homologous with the amino
      terminal three SCR in human DAF, a serine/threonine-rich (ST) region, and
      sequence compatible with a transmembrane domain and cytoplasmic tail. Northern
      blot and RT-PCR analysis showed that pig DAF was expressed in a wide range of
      tissues. Additional isoforms of DAF were sought using RT-PCR and 3'-rapid
      amplification of cDNA ends followed by sequencing. Isoforms containing a GPI
      anchor and with differing lengths of ST region were identified; no isoform
      containing a fourth SCR was found. Cloning of the GPI-anchored isoform from
      granulocytes confirmed that it was identical with the original transmembrane
      isoform through the three SCR and first portion of ST and was derived from a
      frame shift caused by splicing out 176 bp of sequence. A panel of mAbs was
      generated and used to analyze the distribution and anchoring of pig DAF in
      circulating cells. Pig DAF was expressed on all circulating cells and was
      transmembrane anchored on erythrocytes, but completely or partially GPI anchored
      on granulocytes and mononuclear cells. The transmembrane isoform of pig DAF was
      expressed on Chinese hamster ovary cells and was shown to affect regulatory
      activity for the classical pathway of human complement, but was only marginally
      active against pig serum.

PMID- 10946284
TI  - Effect of integrin beta 2 subunit truncations on LFA-1 (CD11a/CD18) and Mac-1
      (CD11b/CD18) assembly, surface expression, and function.
AB  - LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) are members of the beta2 integrins
      involved in leukocyte function during immune and inflammatory responses. We aimed
      to determine a minimized beta2 subunit that forms functional LFA-1 and Mac-1.
      Using a series of truncated beta2 variants, we showed that the subregion Q23-D300
      of the beta2 subunit is sufficient to combine with the alphaL and alphaM subunits
      intracellularly. However, only the beta2 variants terminating after Q444 promote
      cell surface expression of LFA-1 and Mac-1. Thus, the major cysteine-rich region
      and the three highly conserved cysteine residues at positions 445, 447, and 449
      of the beta2 subunit are not required for LFA-1 and Mac-1 surface expression. The
      surface-expressed LFA-1 variants are constitutively active with respect to ICAM-1
      adhesion and these variants express the activation reporter epitope of the mAb
      24. In contrast, surface-expressed Mac-1, both the wild type and variants,
      require 0. 5 mM MnCl2 for adhesion to denatured BSA. These results suggest that
      the role of the beta2 subunit in LFA-1- and Mac-1-mediated adhesion may be
      different.

PMID- 10946285
TI  - Saturation, competition, and specificity in interaction of heat shock proteins
      (hsp) gp96, hsp90, and hsp70 with CD11b+ cells.
AB  - Heat shock proteins (hsp(s)) have been postulated to interact with APCs through
      specific receptors, although the receptors are yet to be identified. Specificity,
      saturation, and competition are the three defining attributes of a receptor
      ligand interaction. We demonstrate here that the interaction of the heat shock
      proteins gp96 and hsp90 with CD11b+ cells is specific and saturable and that gp96
      can compete with itself in gp96-macrophage interaction. Interestingly, the
      phylogenetically related hsp90 also competes quite effectively with gp96 for
      binding to macrophages, whereas the unrelated hsp70 does so relatively poorly,
      although it binds CD11b+ cells just as effectively. These data provide evidence
      that the heat shock proteins interact with APCs with specificity and for the
      existence of at least two distinct receptors, one for gp96 and hsp90 and the
      other for hsp70.

PMID- 10946286
TI  - Molecular cloning and characterization of a novel CXC chemokine macrophage
      inflammatory protein-2 gamma chemoattractant for human neutrophils and dendritic
      cells.
AB  - Chemokines play important roles in leukocyte trafficking as well as function
      regulation. In this study, we described the identification and characterization
      of a novel CXC chemokine from a human dendritic cell (DC) cDNA library, the full
      length cDNA of which contains an open reading frame encoding 111 aa with a
      putative signal peptide of 34 aa. This CXC chemokine shares greatest homology
      with macrophage inflammatory protein (MIP)-2alphabeta, hence is designated as MIP
      2gamma. Mouse MIP-2gamma was identified by electrocloning and is highly
      homologous to human MIP-2gamma. Northern blotting revealed that MIP-2gamma was
      constitutively and widely expressed in most normal tissues with the greatest
      expression in kidney, but undetectable in most tumor cell lines except THP-1
      cells. In situ hybridization analysis demonstrated that MIP-2gamma was mainly
      expressed by the epithelium of tubules in the kidney and hepatocytes in the
      liver. Although no detectable expression was observed in freshly isolated or PMA
      treated monocytes, RT-PCR analysis revealed MIP-2gamma expression by monocyte
      derived DC. Recombinant MIP-2gamma from 293 cells is about 9.5 kDa in size and
      specifically detectable by its polyclonal Ab developed by the immunization with
      its 6His-tagged fusion protein. The eukaryotically expressed MIP-2gamma is a
      potent chemoattractant for neutrophils, and weaker for DC, but inactive to
      monocytes, NK cells, and T and B lymphocytes. Receptor binding assays showed that
      MIP-2gamma does not bind to CXCR2. This implies that DC might contribute to the
      innate immunity through the production of neutrophil-attracting chemokines and
      extends the knowledge about the regulation of DC migration.

PMID- 10946287
TI  - Mycobacterium tuberculosis infection in complement receptor 3-deficient mice.
AB  - Complement receptor type 3 (CR3) present on macrophages is used by Mycobacterium
      tuberculosis as one of its major phagocytic receptors. In this study, we examined
      the in vivo significance of CR3-mediated phagocytosis on the pathogenesis of
      disease caused by M. tuberculosis. The outcome of tuberculous infection in mice
      deficient in the CD11b subunit of CR3 (CR3-/-) on a mixed 129SV and C57BL
      background and control wild-type counterparts was comparable with respect to
      survival, bacterial burden, granulomatous lesion development, and cytokine
      expression in the spleen and lungs. M. tuberculosis infection was also examined
      in CR3-/- mice on C57BL/6 and BALB/c backgrounds and was found to be similar. In
      conclusion, our results suggest that in the absence of CR3, M. tuberculosis is
      able to gain entry into host cells via alternative phagocytic receptors and
      establish infection. The data also indicate that absence of CR3 does not alter
      disease course in either the relatively resistant C57BL/6 or the relatively
      susceptible BALB/c strains of mice.

PMID- 10946288
TI  - Enhanced pulmonary allergic responses to Aspergillus in CCR2-/- mice.
AB  - Allergic responses to Aspergillus species exacerbate asthma and cystic fibrosis.
      The natural defense against live Aspergillus fumigatus spores or conidia depends
      on the recruitment and activation of mononuclear and polymorphonuclear
      leukocytes, events that are dependent on chemotactic cytokines. In this study, we
      explored the relative contribution of the monocyte chemoattractant protein-1
      receptor, CCR2, in the pulmonary response to A. fumigatus conidia. Following
      sensitization to soluble A. fumigatus Ags, mice lacking CCR2 due to targeted
      deletion were markedly more susceptible to the injurious effects of an
      intrapulmonary challenge with live conidia compared with mice that expressed CCR2
      or CCR2+/+. CCR2-/- mice exhibited a major defect in the recruitment of
      polymorphonuclear cells, but these mice also had significantly more eosinophils
      and lymphocytes in bronchoalveolar lavage samples. CCR2-/- mice also had
      significant increases in serum levels of total IgE and whole lung levels of IL-5,
      IL-13, eotaxin, and RANTES compared with CCR2+/+ mice. Airway inflammation, hyper
      responsiveness to spasmogens, and subepithelial fibrosis were significantly
      enhanced in CCR2-/- mice compared with CCR2+/+ mice after the conidia challenge.
      Thus, these findings demonstrate that CCR2 plays an important role in the immune
      response against A. fumigatus, thereby limiting the allergic airway inflammatory
      and remodeling responses to this fungus.

PMID- 10946289
TI  - Expression of the cytolethal distending toxin (Cdt) operon in Actinobacillus
      actinomycetemcomitans: evidence that the CdtB protein is responsible for G2
      arrest of the cell cycle in human T cells.
AB  - We have previously shown that Actinobacillus actinomycetemcomitans produces an
      immunosuppressive factor that is encoded by the cdtB gene, which is homologous to
      a family of cytolethal distending toxins (Cdt) expressed by several gram-negative
      bacteria. In this study, we report that the cdt locus in A. actinomycetemcomitans
      is composed of five open reading frames, designated orf1, orf2, cdtA, cdtB, and
      cdtC. The deduced amino acid sequences of the five open reading frames are highly
      conserved among A. actinomycetemcomitans strains 652, Y4, 29522, and HK1651.
      There is also strong homology with the Cdt proteins of Haemophilus ducreyi (87
      91%), but only partial homology with that of Campylobacter jejuni and Escherichia
      coli (29-48%). Analysis of A. actinomycetemcomitans mRNA by RT-PCR suggests that
      the two small open reading frames upstream of cdtA are coexpressed with cdtA,
      cdtB, and cdtC. We next utilized a series of plasmids that express various
      combinations of the cdt genes to determine their requirement for expression of
      immunoinhibitory activity. Cell extracts of E. coli transformed with each of the
      plasmids were tested for their capacity to induce G2 arrest in the cell cycle of
      PHA-activated human T cells. These experiments suggest that expression of cdtB
      alone is sufficient to induce G2 arrest in human T cells, but do not exclude the
      possibility that cdtC also contributes to cell cycle arrest. The implications of
      our results with respect to the function of the individual Cdt proteins are
      discussed.

PMID- 10946290
TI  - Identification of STAT4-dependent and independent mechanisms of resistance to
      Toxoplasma gondii.
AB  - The capacity of IL-12 to stimulate T and NK cell production of IFN-gamma is
      required for resistance to Toxoplasma gondii. To identify the transcription
      factors involved in this mechanism of resistance, mice deficient in STAT4, a
      protein involved in IL-12 signaling, were infected with T. gondii and their
      immune responses were analyzed. STAT4-/- mice were unable to control parasite
      replication and died during the acute phase of infection, whereas wild-type mice
      controlled parasite replication and survived this challenge. The susceptibility
      of STAT4-/- mice to toxoplasmosis correlated with a defect in their ability to
      produce IFN-gamma in response to infection, whereas administration of IFN-gamma
      to these mice inhibited parasite replication and delayed time to death.
      Interestingly, analysis of infected STAT4-/- mice revealed that these mice did
      produce low levels of IFN-gamma during infection, and the ability of splenocytes
      from infected or uninfected STAT4-/- mice to produce IFN-gamma was enhanced by
      the addition of IL-2 plus IL-18. Moreover, administration of IL-2 plus IL-18 to
      STAT4-/- mice resulted in elevated serum levels of IFN-gamma associated with a
      decreased parasite burden and delayed time to death. In vivo depletion studies
      demonstrated that the ability of IL-2 plus IL-18 to mediate STAT4-independent
      resistance to T. gondii is dependent on NK cell production of IFN-gamma.
      Together, these studies identify STAT4 as an important transcription factor
      required for development of the innate NK and adaptive T cell responses necessary
      for resistance to T. gondii. However, other signaling pathways can be used to
      bypass STAT4-dependent production of IFN-gamma and enhance innate resistance to
      T. gondii.

PMID- 10946291
TI  - An immunomodulatory function for neutrophils during the induction of a CD4+ Th2
      response in BALB/c mice infected with Leishmania major.
AB  - The possible immunomodulatory role of polymorphonuclear leukocytes (PMN) in CD4+
      T lymphocyte differentiation in mice was examined by studying the effect of
      transient depletion of PMN during the early phase after Leishmania major
      delivery. A single injection of the PMN-depleting NIMP-R14 mAb 6 h before
      infection with L. major prevented the early burst of IL-4 mRNA transcription
      otherwise occurring in the draining lymph node of susceptible BALB/c mice. Since
      this early burst of IL-4 mRNA transcripts had previously been shown to instruct
      Th2 differentiation in mice from this strain, we examined the effect of PMN
      depletion on Th subset differentiation at later time points after infection. The
      transient depletion of PMN in BALB/c mice was sufficient to inhibit Th2 cell
      development otherwise occurring after L. major infection. Decreased Th2 responses
      were paralleled with partial resolution of the footpad lesions induced by L.
      major. Furthermore, draining lymph node-derived CD4+ T cells from PMN-depleted
      mice remained responsive to IL-12 after L. major infection, unlike those of
      infected BALB/c mice receiving control Ab. PMN depletion had no effect when the
      NIMP-R14 mAb was injected 24 h postinfection. The protective effect of PMN
      depletion was shown to be IL-12 dependent, as concomitant neutralization of IL-12
      reversed the protective effect of PMN depletion. These results suggest a role for
      an early wave of PMN in the development of the Th2 response characteristic of
      mice susceptible to infection with L. major.

PMID- 10946292
TI  - Proteolytic activities of two types of mannose-binding lectin-associated serine
      protease.
AB  - Mannose (or mannan)-binding lectin (MBL) is an oligomeric serum lectin that plays
      a role in innate immunity by activating the complement system. In human, two
      types of MBL-associated serine protease (MASP-1 and MASP-2) and a truncated
      protein of MASP-2 (small MBL-associated protein; sMAP or MAp19) are complexed
      with MBL. To clarify the proteolytic activities of MASP-1 and MASP-2 against C4,
      C2, and C3, we isolated these two types of MASP in activated forms from human
      serum by sequential affinity chromatography. On an anti-MASP-1 column, MASP-2
      passed through the column in the presence of EDTA and high salt concentration,
      whereas MASP-1 was retained. Isolated MASP-1 and MASP-2 exhibited proteolytic
      activities against C3 and C4, respectively. C2 was activated by both MASPs. C1
      inhibitor (C1 INH), an inhibitor for C1r and C1s, formed equimolar complexes with
      MASP-1 and MASP-2 and inhibited their proteolytic activities.

PMID- 10946293
TI  - Gamma delta-T cells are critical for survival and early proinflammatory cytokine
      gene expression during murine Klebsiella pneumonia.
AB  - Although cells of the innate inflammatory response, such as macrophages and
      neutrophils, have been extensively studied in the arena of Gram-negative
      bacterial pneumonia, a role for T cells remains unknown. To study the role of
      specific T cell populations in bacterial pneumonia, mice deleted of their TCR
      beta- and/or delta-chain were intratracheally inoculated with Klebsiella
      pneumoniae. Gamma delta T cell knockout mice displayed increased mortality at
      both early and late time points. In contrast, mice specifically lacking only
      alpha beta-T cells were no more susceptible than wild-type mice. Pulmonary
      bacterial clearance in gamma delta-T cell knockout mice was unimpaired.
      Interestingly, these mice displayed increased peripheral blood dissemination.
      Rapid up-regulation of IFN-gamma and TNF-alpha gene expression, critical during
      bacterial infections, was markedly impaired in lung and liver tissue from gamma
      delta-T cell-deficient mice 24 h postinfection. The increased peripheral blood
      bacterial dissemination correlated with impaired hepatic bacterial clearance
      following pulmonary infection and increased hepatic injury as measured by plasma
      aspartate aminotransferase activity. Combined, these data suggest that mice
      lacking gamma delta-T cells have an impaired ability to resolve disseminated
      bacterial infections subsequent to the initial pulmonary infection. These data
      indicate that gamma delta-T cells comprise a critical component of the acute
      inflammatory response toward extracellular Gram-negative bacterial infections and
      are vital for the early production of the proinflammatory cytokines IFN-gamma and
      TNF-alpha.

PMID- 10946294
TI  - Relevance of the tumor antigen in the validation of three vaccination strategies
      for melanoma.
AB  - Many preclinical studies of cancer immunotherapy are based on the testing of a
      single vaccination strategy in several tumor models. Moreover, most of those
      studies used xenogeneic Ags, which, owing to their high immunogenicity, may not
      represent realistic models for the validation of cancer immunotherapies. To
      address these issues, we compared the vaccination efficacy of three well
      established strategies (i.e., naked DNA; peptide-pulsed dendritic cells (DC), or
      a mixture of peptide and the Escherichia coli toxin LTR72) using the xenogeneic
      OVA or the naturally expressed tyrosinase-related protein 2 (TRP-2) tumor Ag in
      the B16 melanoma model. C57BL/6 mice received one to three s.c. injections of
      peptide-pulsed DC or DNA, or one to four mucosal administrations of peptide-toxin
      mixture. One to 2 wk later, the animals were challenged s.c. with B16 or B16
      cells expressing OVA (B16-OVA). Vaccination of mice with OVA induced in all cases
      melanoma-specific CTL and protection against B16-OVA. When TRP-2 was used, all
      three vaccines elicited B16-specific CTL, but only DC pulsed with the
      immunodominant T cell epitope TRP-2181-188 allowed protection against B16. Even
      more importantly, a vaccination regimen with TRP-2-pulsed DC, started 24 h after
      the injection of a lethal number of B16 cells, caused a therapeutic effect in 60%
      of the challenged animals. Our results strongly emphasize the relevance of the
      tumor Ag in the definition of immunotherapeutic strategies for cancer, and
      support the use of peptide-pulsed DC as cancer vaccine in humans.

PMID- 10946295
TI  - Regulation of infection with Histoplasma capsulatum by TNFR1 and -2.
AB  - The concerted action of several cytokines is necessary for resolution of both
      primary and secondary infection with Histoplasma capsulatum. Among the soluble
      factors that contribute to tissue sterilization, TNF-alpha stands as a central
      mediator of protective immunity to this fungus. In this study, we explored the
      regulation of protective immunity by TNFR1 and -2. In primary pulmonary
      infection, both TNFR1-/- and -2-/- mice manifested a high mortality after
      infection with H. capsulatum, although TNFR1-/- mice were more susceptible than
      TNFR2 -/- mice. Overwhelming infection in the former was associated with a
      pronounced decrement in the number of inflammatory cells in the lungs and
      elevated IFN-gamma and TNF-alpha levels in the lungs. In contrast, IFN-gamma
      levels were markedly decreased in TNFR2-/- mice, and treatment with this cytokine
      restored protective immunity. Lung macrophages from both groups of knockout mice
      released substantial amounts of NO. Upon secondary infection, TNFR2-/- mice
      survived rechallenge and cleared infection as efficiently as C57BL/6 animals. In
      contrast, mice given mAb to TNFR1 succumbed to reexposure, and the high mortality
      was accompanied by a significant increase in fungal burden in the lungs. Both IL
      4 and IL-10 were elevated in the lungs of these mice. The results demonstrate the
      pivotal influence of TNFR1 and -2 in controlling primary infection and highlight
      the differences between these receptors for regulation reexposure histoplasmosis.

PMID- 10946296
TI  - The anti-tumor activity of IL-12: mechanisms of innate immunity that are model
      and dose dependent.
AB  - IL-12 has been demonstrated to have potent anti-tumor activities in a variety of
      mouse tumor models, but the relative roles of NK, NKT, and T cells and their
      effector mechanisms in these responses have not been fully addressed. Using a
      spectrum of gene-targeted or Ab-treated mice we have shown that for any
      particular tumor model the effector mechanisms downstream of IL-12 often mimic
      the natural immune response to that tumor. For example, metastasis of the MHC
      class I-deficient lymphoma, EL4-S3, was strictly controlled by NK cells using
      perforin either naturally or following therapy with high-dose IL-12.
      Intriguingly, in B16F10 and RM-1 tumor models both NK and NKT cells contribute to
      natural protection from tumor metastasis. In these models, a lower dose of IL-12
      or delayed administration of IL-12 dictated a greater relative role of NKT cells
      in immune protection from tumor metastasis. Overall, both NK and NKT cells can
      contribute to natural and IL-12-induced immunity against tumors, and the relative
      role of each population is tumor and therapy dependent.

PMID- 10946297
TI  - JNK1 is required for T cell-mediated immunity against Leishmania major infection.
AB  - c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that plays
      important regulatory roles in helper T cell differentiation. In the current
      study, we used Jnk1-deficient mice to examine the function of JNK during an in
      vivo pathogenic infection, leishmaniasis, which is strongly influenced by Th1/Th2
      effector mechanisms. The data show that Jnk1-deficient mice, despite their
      usually genetically resistant background, were unable to resolve Leishmania
      infections. Jnk1-/- mice displayed reduced delayed-type hypersensitivity in
      response to the pathogen, which was associated with a T cell defect. We found
      that, although these mice can direct an apparent Th1-response, there is also
      simultaneous generation of Leishmania-specific Th2 responses, which possibly down
      modulate protective Th1-mediated immune function. These findings demonstrate that
      the negative regulation of Th2 cytokine production by the JNK1 signaling pathway
      is essential for generating Th1-polarized immunity against intracellular
      pathogens, such as Leishmania major.

PMID- 10946298
TI  - The chemokine macrophage-inflammatory protein-1 alpha and its receptor CCR1
      control pulmonary inflammation and antiviral host defense in paramyxovirus
      infection.
AB  - In this work, we explore the responses of specific gene-deleted mice to infection
      with the paramyxovirus pneumonia virus of mice (PVM). We have shown previously
      that infection of wild type mice with PVM results in pulmonary neutrophilia and
      eosinophilia accompanied by local production of macrophage-inflammatory protein-1
      alpha (MIP-1 alpha). Here we examine the role of MIP-1 alpha in the pathogenesis
      of this disease using mice deficient in MIP-1 alpha or its receptor, CCR1. The
      inflammatory response to PVM in MIP-1 alpha-deficient mice was minimal, with
      approximately 10-60 neutrophils/ml and no eosinophils detected in bronchoalveolar
      lavage fluid. Higher levels of infectious virus were recovered from lung tissue
      excised from MIP-1 alpha-deficient than from fully competent mice, suggesting
      that the inflammatory response limits the rate of virus replication in vivo. PVM
      infection of CCR1-deficient mice was also associated with attenuated
      inflammation, with enhanced recovery of infectious virus, and with accelerated
      mortality. These results suggest that the MIP-1 alpha/CCR1-mediated acute
      inflammatory response protects mice by delaying the lethal sequelae of infection.

PMID- 10946299
TI  - Involvement of lipopolysaccharide binding protein, CD14, and Toll-like receptors
      in the initiation of innate immune responses by Treponema glycolipids.
AB  - Culture supernatants from Treponema maltophilum associated with periodontitis in
      humans and Treponema brennaborense found in a bovine cattle disease accompanied
      with cachexia caused a dose-dependent TNF-alpha synthesis in human monocytes
      increasing with culture time. This activity could be reduced significantly by
      blocking the CD14-part of the LPS receptor using the My 4 mAb and by polymyxin B.
      In the murine macrophage cell line RAW 264.7, Treponema culture supernatants
      induced TNF-alpha secretion in a LPS binding protein (LBP)-dependent fashion. To
      enrich for active compounds, supernatants were extracted with butanol, while
      whole cells were extracted using a phenol/water method resulting in recovery of
      material exhibiting a similar activity profile. An LPS-LBP binding competition
      assay revealed an interaction of the treponeme phenol/water extracts with LBP,
      while precipitation studies implied an affinity to polymyxin B and endotoxin
      neutralizing protein. Macrophages obtained from C3H/HeJ mice carrying a Toll-like
      receptor (TLR)-4 mutation were stimulated with treponeme extracts for NO release
      to assess the role of TLRs in cell activation. Furthermore, NF-kappaB
      translocation in TLR-2-negative Chinese hamster ovary (CHO) cells was studied. We
      found that phenol/water-extracts of the two strains use TLRs differently with T.
      brennaborense-stimulating cells in a TLR-4-dependent fashion, while T.
      maltophilum-mediated activation apparently involved TLR-2. These results indicate
      the presence of a novel class of glycolipids in Treponema initiating inflammatory
      responses involving LBP, CD14, and TLRs.

PMID- 10946300
TI  - Differential regulation of responsiveness to fMLP and C5a upon dendritic cell
      maturation: correlation with receptor expression.
AB  - The trafficking of immature and mature dendritic cells (DCs) to different
      anatomical sites in vivo is critical for fulfilling their roles in the induction
      of Ag-specific immune responses. Although this process is complex and regulated
      by many mediators, the capacity of DCs to migrate is predominantly dependent on
      the expression of particular chemotactic receptors on the surface of DCs that
      enable them to move along chemotactic gradients formed by the corresponding
      chemokines and/or classical chemoattractants. Here we show that immature DCs
      (iDCs) respond to both fMLP and C5a as determined by chemotaxis and Ca2+
      mobilization, whereas mature DCs (mDCs) respond to C5a, but not fMLP.
      Additionally, iDCs express the receptors for both fMLP and C5a at mRNA and
      protein levels. Upon maturation of DCs, fMLP receptor expression is almost
      completely absent, whereas C5a receptor mRNA and protein expression is
      maintained. Concomitantly, mDCs migrate chemotactically and mobilize
      intracellular Ca2+ in response to C5a, but not fMLP. Thus the interaction between
      C5a and its receptor is likely involved in the regulation of trafficking of both
      iDCs and mDCs, whereas fMLP mobilizes only iDCs. The differential responsiveness
      to fMLP and C5a of iDCs and mDCs suggests that they play different roles in the
      initiation of immune responses.

PMID- 10946301
TI  - The role of a mitochondrial pathway in the induction of apoptosis by chemicals
      extracted from diesel exhaust particles.
AB  - We are interested in the cytotoxic and proinflammatory effects of particulate
      pollutants in the respiratory tract. We demonstrate that methanol extracts made
      from diesel exhaust particles (DEP) induce apoptosis and reactive oxygen species
      (ROS) in pulmonary alveolar macrophages and RAW 264.7 cells. The toxicity of
      these organic extracts mimics the cytotoxicity of the intact particles and could
      be suppressed by the synthetic sulfhydryl compounds, N-acetylcysteine and
      bucillamine. Because DEP-induced apoptosis follows cytochrome c release, we
      studied the effect of DEP chemicals on mitochondrially regulated death
      mechanisms. Crude DEP extracts induced ROS production and perturbed mitochondrial
      function before and at the onset of apoptosis. This mitochondrial perturbation
      follows an orderly sequence of events, which commence with a change in
      mitochondrial membrane potential, followed by cytochrome c release, development
      of membrane asymmetry (annexin V staining), and propidium iodide uptake.
      Structural damage to the mitochondrial inner membrane, evidenced by a decrease in
      cardiolipin mass, leads to O-*2 generation and uncoupling of oxidative
      phosphorylation (decreased intracellular ATP levels). N-acetylcysteine reversed
      these mitochondrial effects and ROS production. Overexpression of the
      mitochondrial apoptosis regulator, Bcl-2, delayed but did not suppress apoptosis.
      Taken together, these results suggest that DEP chemicals induce apoptosis in
      macrophages via a toxic effect on mitochondria.

PMID- 10946302
TI  - Simvastatin modulates cytokine-mediated endothelial cell adhesion molecule
      induction: involvement of an inhibitory G protein.
AB  - Endothelial cell adhesion molecules (CAMs) E-selectin, ICAM-1, and VCAM-1 play
      variably important roles in immune-mediated processes. They are induced by the
      proinflammatory cytokines IL-1 and TNF-alpha, and NF-kappaB is required for the
      regulated expression of all three genes. Regulators of this pathway could
      potentially be potent immune modulators. We studied the effect of a 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor, simvastatin, on cytokine-induced
      expression of CAMs in HUVEC. Unexpectedly, pretreatment with simvastatin
      potentiated the induction of all three endothelial CAMs by IL-1 and TNF, but not
      LPS or PMA, as detected by flow cytometry. Northern blot analysis demonstrated an
      increase in steady state IL-1-induced E-selectin mRNA levels in cells pretreated
      with simvastatin. This was associated with an increase in nuclear translocation
      of NF-kappaB, as detected by EMSA. The effect of simvastatin was reversed by
      mevalonate and geranylgeranyl pyrophosphate but not squalene, indicating that an
      inhibitory prenylated protein is involved in endothelial responses to
      proinflammatory cytokines. Pertussis toxin mimicked the effect of simvastatin,
      and the G protein activator NaF inhibited the cytokine-induced expression of
      endothelial CAMs, indicating that a Gialpha protein is involved. These results
      demonstrate that cytokine-mediated activation of the endothelium, and
      specifically CAM induction, can be modulated by a heterotrimeric G protein
      coupled pathway. This may represent a "basal tone" of endothelial inactivation,
      which can either be disinhibited or amplified, depending on the stimulus.

PMID- 10946303
TI  - TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells:
      involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine
      kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway.
AB  - TNF-alpha induced a dose- and time-dependent increase in cyclooxygenase-2 (COX-2)
      expression and PGE2 formation in human NCI-H292 epithelial cells.
      Immunofluorescence staining demonstrated that COX-2 was expressed in cytosol and
      nuclear envelope. Tyrosine kinase inhibitors (genistein or herbimycin) or
      phosphoinositide-specific phospholipase C inhibitor (U73122) blocked TNF-alpha
      induced COX-2 expression. TNF-alpha also stimulated phosphatidylinositol
      hydrolysis and protein kinase C (PKC) activity, and both were abolished by
      genistein or U73122. The PKC inhibitor, staurosporine, also inhibited TNF-alpha
      induced response. The 12-O-tetradecanoylphorbol 13-acetate (TPA), a PKC
      activator, also stimulated COX-2 expression, this effect being inhibited by
      genistein or herbimycin. NF-kappaB DNA-protein binding and COX-2 promoter
      activity were enhanced by TNF-alpha, and these effects were inhibited by
      genistein, U73122, staurosporine, or pyrolidine dithiocarbamate. TPA stimulated
      both NF-kappaB DNA-protein binding and COX-2 promoter activity, these effects
      being inhibited by genistein, herbimycin, or pyrolidine dithiocarbamate. The TNF
      alpha-induced, but not the TPA-induced, COX-2 promoter activity was inhibited by
      phospholipase C-gamma2 mutants, and the COX-2 promoter activity induced by either
      agent was attenuated by dominant-negative mutants of PKC-alpha, NF-kappaB
      inducing kinase, or I-kappaB (inhibitory protein that dissociates from NF-kappaB)
      kinase (IKK)1 or 2. IKK activity was stimulated by both TNF-alpha and TPA, and
      these effects were inhibited by staurosporine or herbimycin. These results
      suggest that, in NCI-H292 epithelial cells, TNF-alpha might activate
      phospholipase C-gamma2 via an upstream tyrosine kinase to induce activation of
      PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappaB
      inducing kinase and IKK1/2, and NF-kappaB in the COX-2 promoter, then initiation
      of COX-2 expression and PGE2 release.

PMID- 10946304
TI  - Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line.
AB  - The antiapoptotic molecule Bcl-xL has been implicated in the differentiation and
      survival of activated macrophages in inflammatory conditions. In this report, the
      role of Bcl-xL in LPS-induced cytokine gene expression and secretion was studied.
      Bcl-xL-transfected RAW 264 macrophages were protected from gliotoxin-induced
      apoptosis, indicating the presence of functional Bcl-xL. Overexpression of Bcl-xL
      in this macrophage cell line was also associated with a marked inhibition of LPS
      induced TNF-alpha, JE/monocyte chemoattractant protein 1, and macrophage
      inflammatory protein 2 secretion. Inhibition of LPS-induced cytokine secretion
      was paralleled by a decrease in levels of steady-state mRNA for the above
      cytokines and for IL-1beta. Decreased production of TNF-alpha in Bcl-xL
      transfectants was not due to increased mRNA degradation, as the mRNA half-lives
      were the same in Bcl-xL transfectants and control macrophages. Although the
      composition of NF-kappaB complexes detected by EMSA and supershift analysis in
      nuclear lysates derived from Bcl-xL transfectants and control cells was
      indistinguishable, LPS-induced inhibitory kappaBalpha degradation, as well as NF
      kappaB binding and AP-1 activation, were slightly decreased by ectopic expression
      of Bcl-xL. More strikingly, LPS-induced phosphorylation of p38 mitogen-activated
      protein kinase and c-Jun N-terminal kinase was strongly repressed by Bcl-xL
      overexpression, offering a possible mechanism for the inhibition of LPS-induced
      cytokine production. These data provide the first evidence for a novel role for
      Bcl-xL as an anti-inflammatory mediator in macrophages.

PMID- 10946305
TI  - TNF-alpha associated with extracellular matrix fibronectin provides a stop signal
      for chemotactically migrating T cells.
AB  - The migration of T cells into extravascular sites of inflammation is regulated by
      information derived from the molecular structure of the invaded tissue and from
      chemokine and cytokine gradients in the context of the extracellular matrix
      (ECM). Although recent studies have highlighted the role of particular
      chemoattractants in leukocyte migration, to date little is known about how
      specific combinations of contextual signals control the migration of leukocytes
      and their localization at sites of inflammation. Here we studied the interplay
      between a pleiotropic cytokine, TNF-alpha, and two prototypic chemoattractants,
      RANTES and stromal cell-derived factor-1alpha (SDF-1alpha), on human CD45RO+ T
      cells migrating within an ECM-like context. For this purpose, we used a newly
      constructed three-dimensional gel system designed to follow, in real time, the
      migration of individual leukocytes along chemotactic gradients in vitro. We found
      that TNF-alpha, which binds the ECM protein fibronectin and lacks adhesion- and
      migration-promoting effects of its own, can act as a proadhesive cytokine on T
      cells exposed to RANTES and SDF-1alpha. Furthermore, fibronectin-complexed TNF
      alpha provided anchorage signals to the T cells as they moved directionally along
      chemoattractive gradients. This effect of TNF-alpha required an intact TNF-alpha
      receptor II subtype on the migrating T cells. The anchoring effect of TNF-alpha
      appears to be specific; IL-2, an integrin-activating proadhesive cytokine, does
      not transmit stoppage signals to T cell migration induced by RANTES. Thus, TNF
      alpha present in the ECM at sites of inflammation may function to anchor T cells
      recruited to these sites by chemotactic signals.

PMID- 10946306
TI  - CCR3-active chemokines promote rapid detachment of eosinophils from VCAM-1 in
      vitro.
AB  - Selective eosinophil recruitment is the result of orchestrated events involving
      cell adhesion molecules, chemokines, and their receptors. The mechanisms by which
      chemokines regulate eosinophil adhesion and migration via integrins are not fully
      understood. In our study, we examined the effect of CCR3-active chemokines on
      eosinophil adhesion to VCAM-1 and BSA under both static and flow conditions. When
      eotaxin-2 or other CCR3-active chemokines were added to adherent eosinophils, it
      induced rapid and sustained eosinophil detachment from VCAM-1 in a concentration
      dependent manner. Adhesion was detectably reduced within 3 min and was further
      reduced at 10-60 min. Simultaneously, eotaxin-2 enhanced eosinophil adhesion to
      BSA. Preincubation of eosinophils with the CCR3-blocking mAb 7B11 completely
      prevented chemokine-induced changes in adhesion to VCAM-1 and BSA. Using a
      different protocol, pretreatment of eosinophils with chemokines for 0-30 min
      before their use in adhesion assays resulted in inhibition of VCAM-1 adhesion and
      enhancement of BSA adhesion. By flow cytometry, expression of alpha4 integrins
      and a beta1 integrin activation epitope on eosinophils was decreased by eotaxin
      2. In a flow-based adhesion assay, eotaxin-2 reduced eosinophil accumulation and
      the strength of attachment to VCAM-1. These results show that eotaxin-2 rapidly
      reduced alpha4 integrin function while increasing beta2 integrin function. These
      findings suggest that chemokines facilitate migration of eosinophils by shifting
      usage away from beta1 integrins toward beta2 integrins.

PMID- 10946308
TI  - Activation of human leukocytes reduces surface P-selectin glycoprotein ligand-1
      (PSGL-1, CD162) and adhesion to P-selectin in vitro.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1), the primary ligand for P-selectin, is
      constitutively expressed on the surface of circulating leukocytes. The objective
      of this study was to examine the effect of leukocyte activation on PSGL-1
      expression and PSGL-1-mediated leukocyte adhesion to P-selectin. PSGL-1
      expression was examined via indirect immunofluorescence and flow cytometry before
      and after leukocyte stimulation with platelet activating factor (PAF) and PMA.
      Human neutrophils, monocytes, and eosinophils were all demonstrated to have
      significant surface expression of PSGL-1 at baseline, which decreased within
      minutes of exposure to PAF or PMA. PSGL-1 was detected in the supernatants of PAF
      activated neutrophils by immunoprecipitation. Along with the expression data,
      this suggests removal of PSGL-1 from the cell surface. Soluble PSGL-1 was also
      detected in human bronchoalveolar lavage fluids. Down-regulation of PSGL-1 was
      inhibited by EDTA. However, inhibitors of L-selectin shedding and other sheddase
      inhibitors did not affect PSGL-1 release, suggesting that PSGL-1 may be shed by
      an as yet unidentified sheddase or removed by some other mechanism. Functionally,
      PSGL-1 down-regulation was associated with decreased neutrophil adhesion to
      immobilized P-selectin under both static and flow conditions, with the most
      profound effects seen under flow conditions. Together, these data indicate that
      PSGL-1 can be removed from the surface of activated leukocytes, and that this
      decrease in PSGL-1 expression has profound effects on leukocyte binding to P
      selectin, especially under conditions of flow.

PMID- 10946307
TI  - Reduction of inflammatory cytokines and prostaglandin E2 by IL-13 gene therapy in
      rheumatoid arthritis synovium.
AB  - The rheumatoid arthritis (RA) joint is characterized by an inflammatory synovial
      pannus which mediates tissue destruction. IL-13 is a cytokine that inhibits
      activated monocytes/macrophages from secreting a variety of proinflammatory
      molecules. The aim of this study was to examine whether gene therapy-delivered IL
      13 could reduce the production of key proinflammatory mediators in RA synovial
      tissue (ST) explants. Adenoviral vectors encoding the genes for human IL-13
      (AxCAIL-13) and bacterial beta-galactosidase were generated and examined for
      protein production. Vectors were used to infect RA ST explants and RA synovial
      fibroblasts, and conditioned medium (CM) was collected at various times for
      analysis by ELISA and competitive immunoassay. AxCAIL-13 decreased the production
      of RA ST explant proinflammatory IL-1beta by 85% after 24 h. Likewise, TNF-alpha
      levels were decreased by 82 and 75% whereas IL-8 levels were reduced 54 and 82%
      after 24 and 48 h, respectively, in RA ST explant CM. Monocyte chemotactic
      protein-1 concentrations were decreased by 88% after 72 h in RA ST explant CM. RA
      ST explant epithelial neutrophil-activating peptide-78 concentrations were
      decreased 85 and 94% whereas growth-related gene product-alpha levels were
      decreased by 77 and 85% at 24 and 48 h, respectively, by AxCAIL-13. Further, IL
      13 significantly decreased PGE2 and macrophage inflammatory protein-1alpha
      production. These results demonstrate that increased expression of IL-13 via gene
      therapy may decrease RA-associated inflammation by reducing secretion of
      proinflammatory cytokines and PGE2.

PMID- 10946309
TI  - Secretory phospholipase A2 receptor-mediated activation of cytosolic
      phospholipase A2 in murine bone marrow-derived mast cells.
AB  - The current study examined the signal transduction steps involved in the
      selective release of arachidonic acid (AA) induced by the addition of secretory
      phospholipase A2 (sPLA2) isotypes to bone marrow-derived mast cells (BMMC).
      Overexpression of sPLA2 receptors caused a marked increase in AA and PGD2 release
      after stimulation of BMMC, implicating sPLA2 receptors in this process. The
      hypothesis that the release of AA by sPLA2 involved activation of cytosolic PLA2
      (cPLA2) was next tested. Addition of group IB PLA2 to BMMC caused a transient
      increase in cPLA2 activity and translocation of this activity to membrane
      fractions. Western analyses revealed that these changes in cPLA2 were accompanied
      by a time-dependent gel shift of cPLA2 induced by phosphorylation of cPLA2 at
      various sites. A noncatalytic ligand of the sPLA2 receptor, p-amino-phenyl-alpha
      D-mannopyranoside BSA, also induced an increase in cPLA2 activity in BMMC. sPLA2
      receptor ligands induced the phosphorylation of p44/p42 mitogen-activated protein
      kinase. Additionally, an inhibitor of p44/p42 mitogen-activated protein kinase
      (PD98059) significantly inhibited sPLA2-induced cPLA2 activation and AA release.
      sPLA2 receptor ligands also increased Ras activation while an inhibitor of
      tyrosine phosphorylation (herbimycin) inhibited the increase in cPLA2 activation
      and AA release. Addition of partially purified sPLA2 from BMMC enhanced cPLA2
      activity and AA release. Similarly, overexpression of mouse groups IIA or V PLA2
      in BMMC induced an increase in AA release. These data suggest that sPLA2 mediate
      the selective release of AA by binding to cell surface receptors and then
      inducing signal transduction events that lead to cPLA2 activation.

PMID- 10946310
TI  - Proinflammatory effects of IL-10 during human endotoxemia.
AB  - IL-10 is considered a potent antiinflammatory cytokine that strongly inhibits the
      production of proinflammatory cytokines. Recent studies have suggested that IL-10
      also has immunostimulatory properties on CD4+, CD8+ T cells, and/or NK cells,
      resulting in increased IFN-gamma production. To determine the effect of IL-10 on
      IFN-gamma production and related inflammatory responses in humans, 16 healthy
      subjects received a bolus i.v. injection of LPS (4 ng/kg) in combination with
      either placebo or recombinant human IL-10 (25 microg/kg), administered just
      before or 1 h after LPS. IL-10 treatment, particularly when administered after
      LPS, enhanced LPS-induced IFN-gamma release, as well as the release of the IFN
      gamma-dependent chemokines IFN-gamma-inducible protein-10 and monokine induced by
      IFN-gamma, while inhibiting or not influencing the production of IFN-gamma
      inducing cytokines. In addition, IL-10 treatment enhanced activation of CTLs and
      NK cells after LPS injection, as reflected by increased levels of soluble
      granzymes. These data indicate that high-dose IL-10 treatment in patients with
      inflammatory disorders can be associated with undesired proinflammatory effects.

PMID- 10946311
TI  - Type IIA secretory phospholipase A2 up-regulates cyclooxygenase-2 and amplifies
      cytokine-mediated prostaglandin production in human rheumatoid synoviocytes.
AB  - Human type IIA secretory phospholipase A2 (sPLA2-IIA) is induced in association
      with several immune-mediated inflammatory conditions. We have evaluated the
      effect of sPLA2-IIA on PG production in primary synovial fibroblasts from
      patients with rheumatoid arthritis (RA). At concentrations found in the synovial
      fluid of RA patients, exogenously added sPLA2-IIA dose-dependently amplified TNF
      alpha-stimulated PGE2 production by cultured synovial fibroblasts. Enhancement of
      TNF-alpha-stimulated PGE2 production in synovial cells was accompanied by
      increased expression of cyclooxygenase (COX)-2 and cytosolic phospholipase A2
      (cPLA2)-alpha. Blockade of COX-2 enzyme activity with the selective inhibitor NS
      398 prevented both TNF-alpha-stimulated and sPLA2-IIA-amplified PGE2 production
      without affecting COX-2 protein induction. However, both sPLA2-IIA-amplified PGE2
      production and enhanced COX-2 expression were blocked by the sPLA2 inhibitor
      LY311727. Colocalization studies using triple-labeling immunofluorescence
      microscopy showed that sPLA2-IIA and cPLA2-alpha are coexpressed with COX-2 in
      discrete populations of CD14-positive synovial macrophages and synovial tissue
      fibroblasts from RA patients. Based on these findings, we propose a model whereby
      the enhanced expression of sPLA2-IIA by RA synovial cells up-regulates TNF-alpha
      mediated PG production via superinduction of COX-2. Therefore, sPLA2-IIA may be a
      critical modulator of cytokine-mediated synovial inflammation in RA.

PMID- 10946312
TI  - IL-10 is induced in the reperfused myocardium and may modulate the reaction to
      injury.
AB  - Reperfusion of the ischemic myocardium is associated with a dramatic inflammatory
      response leading to TNF-alpha release, IL-6 induction, and subsequent neutrophil
      mediated cytotoxic injury. Because inflammation is also an important factor in
      cardiac repair, we hypothesized the presence of components of the inflammatory
      reaction with a possible role in suppressing acute injury. Thus, we investigated
      the role of IL-10, an anti-inflammatory cytokine capable of modulating
      extracellular matrix biosynthesis, following an experimental canine myocardial
      infarction. Using our canine model of myocardial ischemia and reperfusion, we
      demonstrated significant up-regulation of IL-10 mRNA and protein in the ischemic
      and reperfused myocardium. IL-10 expression was first detected at 5 h and peaked
      following 96-120 h of reperfusion. In contrast, IL-4 and IL-13, also associated
      with suppression of acute inflammation and macrophage deactivation, were not
      expressed. In the ischemic canine heart, CD5-positive lymphocytes were the
      predominant source of IL-10 in the myocardial infarct. In the absence of
      reperfusion, no significant induction of IL-10 mRNA was noted. In addition, IL
      12, a Th1-related cytokine associated with macrophage activation, was not
      detected in the ischemic myocardium. In vitro experiments demonstrated late
      postischemic cardiac-lymph-induced tissue inhibitor of metalloproteinases (TIMP)
      1 mRNA expression in isolated canine mononuclear cells. This effect was inhibited
      when the incubation contained a neutralizing Ab to IL-10. Our findings suggest
      that lymphocytes infiltrating the ischemic and reperfused myocardium express IL
      10 and may have a significant role in healing by modulating mononuclear cell
      phenotype and inducing TIMP-1 expression.

PMID- 10946313
TI  - Differential requirement for classic and novel PKC isoforms in respiratory burst
      and phagocytosis in RAW 264.7 cells.
AB  - The binding of Ab (IgG)-opsonized particles by FcgammaRs on macrophages results
      in phagocytosis of the particles and generation of a respiratory burst. Both IgG
      stimulated phagocytosis and respiratory burst involve activation of protein
      kinase C (PKC). However, the specific PKC isoforms required for these responses
      have yet to be identified. We have studied the involvement of PKC isoforms in IgG
      mediated phagocytosis and respiratory burst in the mouse macrophage-like cell
      line, RAW 264.7. Like primary monocyte/macrophages, their IgG-mediated
      phagocytosis was calcium independent and diacylglycerol sensitive, consistent
      with novel PKC activation. Respiratory burst in these cells was Ca2+ dependent
      and inhibited by staurosporine and calphostin C as well as by the classic PKC
      selective inhibitors Go 6976 and CGP 41251, suggesting that classic PKC is
      required. In contrast, phagocytosis was blocked by general PKC inhibitors but not
      by the classic PKC-specific drugs. RAW 264.7 cells expressed PKCs alpha, betaI,
      delta, epsilon, and zeta. Subcellular fractionation demonstrated that PKCs alpha,
      delta, and epsilon translocate to membranes during phagocytosis. In Ca2+-depleted
      cells, only novel PKCs delta and epsilon increased in membranes, and the time
      course of their translocation was consistent with phagosome formation. Confocal
      microscopy of cells transfected with green fluorescent protein-conjugated PKC
      alpha or epsilon confirmed that these isoforms translocated to the forming
      phagosome in Ca-replete cells, but only PKC epsilon colocalized with phagosomes
      in Ca2+-depleted cells. Taken together, these results suggest that the classic
      PKC alpha mediates IgG-stimulated respiratory burst in macrophages, whereas the
      novel PKCs delta and/or epsilon are necessary for phagocytosis.

PMID- 10946314
TI  - The activity of soluble VCAM-1 in angiogenesis stimulated by IL-4 and IL-13.
AB  - IL-13 is a multifunctional lymphokine sharing a number of biological properties
      with IL-4. We previously observed that IL-4 shows angiogenic activities in vitro
      as well as in vivo. In this study we examined the effect of IL-13 on angiogenesis
      in vitro and in vivo and also the underlying mechanisms. Human IL-13
      significantly stimulated the formation of tube-like structures in collagen gels
      by human microvascular endothelial cells and bovine aortic endothelial cells by
      about 3-fold over the controls in the absence of the cytokines. Administration of
      murine IL-13 led to neovascularization when implanted in the rat cornea.
      Coadministration of neutralizing mAb to the IL-4R inhibited both tubular
      morphogenesis in vitro and activation of STAT6 induced by IL-4 or IL-13. Both IL
      4 and IL-13 markedly increased mRNA levels of VCAM-1 in vascular endothelial
      cells, and the production of the soluble form of VCAM-1 was also stimulated in
      response to IL-4 or IL-13. Administration of anti-VCAM-1 Ab in vitro blocked
      tubular morphogenesis induced by IL-4 and IL-13. Angiogenesis induced in vivo in
      rat cornea by IL-4 and IL-13 was also inhibited by Ab against the rat alpha4
      integrin subunit. These findings suggest that angiogenesis dependent on IL-4 and
      IL-13 is mainly mediated through a soluble VCAM-1/alpha4 integrin pathway.

PMID- 10946315
TI  - The autoantibodies to alpha 6 beta 4 integrin of patients affected by ocular
      cicatricial pemphigoid recognize predominantly epitopes within the large
      cytoplasmic domain of human beta 4.
AB  - This study was undertaken to characterize the antigenic determinants recognized
      by the autoantibodies of patients with ocular cicatricial pemphigoid (OCP). OCP
      is a subepithelial, blistering, autoimmune disease that mainly affects the
      conjunctiva and other mucous membranes. We previously demonstrated that a cDNA
      clone, isolated from a keratinocyte expression library by using immunoaffinity
      purified OCP autoantibody, encoded the cytoplasmic domain of beta 4 integrin
      subunit. Our subsequent studies showed that sera from all the OCP patients that
      were tested recognize the human beta 4 integrin subunit. To identify the
      prevalent epitopes of the anti-beta 4 autoantibodies of OCP, we have used cell
      lines transfected with vectors encoding a wild-type beta 4 subunit, a tailless
      beta 4 subunit, or a beta 4 subunit lacking the extracellular domain.
      Nontransfected cell lines were used as controls. Lysates from these cell lines
      were analyzed with OCP sera, IgG fractions from OCP sera, and immunoaffinity
      purified OCP autoantibodies. Abs to extracellular and cytoplasmic domains of
      human beta 4 integrin were used as positive controls, whereas normal human sera
      and normal human IgG fractions were used as negative controls. The reactivity of
      OCP Abs was determined by using immunoblotting, immunoprecipitation, and FACS
      analysis. The results of this study indicate that OCP sera, OCP IgG fractions,
      and immunoaffinity-purified OCP autoantibodies react with the intracellular and
      not the extracellular domain of human beta 4 integrin subunit. In vitro cell
      culture experiments demonstrated that OCP autoantibody binds to the cytoplasm of
      the cells. The relevance of these findings to the pathogenesis of OCP is
      discussed.

PMID- 10946316
TI  - Association of deficient type II protein kinase A activity with aberrant nuclear
      translocation of the RII beta subunit in systemic lupus erythematosus T
      lymphocytes.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder of indeterminate
      etiology characterized by abnormal T cell signal transduction and altered T cell
      effector functions. We have previously observed a profound deficiency of total
      protein kinase A (PKA) phosphotransferase activity in SLE T cells. Here we
      examined whether reduced total PKA activity in SLE T cells is in part the result
      of deficient type II PKA (PKA-II) isozyme activity. The mean PKA-II activity in
      SLE T cells was 61% of normal control T cells. The prevalence of deficient PKA-II
      activity in 35 SLE subjects was 37%. Deficient isozyme activity was persistent
      over time and was unrelated to SLE disease activity. Reduced PKA-II activity was
      associated with spontaneous dissociation of the cytosolic RIIbeta2C2 holoenzyme
      and translocation of the regulatory (RIIbeta) subunit from the cytosol to the
      nucleus. Confocal immunofluorescence microscopy revealed that the RIIbeta subunit
      was present in approximately 60% of SLE T cell nuclei compared with only 2-3% of
      normal and disease controls. Quantification of nuclear RIIbeta subunit protein
      content by immunoprecipitation and immunoblotting demonstrated a 54% increase
      over normal T cell nuclei. Moreover, the RIIbeta subunit was retained in SLE T
      cell nuclei, failed to relocate to the cytosol, and was associated with a
      persistent deficiency of PKA-II activity. In conclusion, we describe a novel
      mechanism of deficient PKA-II isozyme activity due to aberrant nuclear
      translocation of the RIIbeta subunit and its retention in the nucleus in SLE T
      cells. Deficient PKA-II activity may contribute to impaired signaling in SLE T
      cells.

PMID- 10946317
TI  - Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice
      independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules.
AB  - Several death-signaling or death-inducing molecules have been implicated in beta
      cell destruction, including Fas, perforin, and TNFR-1. In this study, we examined
      the role of each death-signaling molecule in the IL-10-accelerated diabetes of
      nonobese diabetic (NOD) mice. Groups of IL-10-NOD mice, each deficient in either
      Fas, perforin, or TNFR-1 molecules, readily developed insulitis, and subsequently
      succumbed to diabetes with an accelerated kinetics and incidence similar to that
      observed in their wild-type or heterozygous IL-10-NOD littermates. Similarly, a
      TNFR-2 deficiency did not block accelerated diabetes in IL-10-NOD mice and
      spontaneous diabetes in NOD mice. These results demonstrate that pancreatic IL-10
      promotes diabetes independent of Fas, perforin, TNFR-1, and TNFR-2 molecules.
      Subsequently, when cyclophosphamide, a diabetes-inducing agent, was injected into
      insulitis-free NOD. lpr/lpr mice, none of these mice developed insulitis or
      diabetes. Our data suggest that cyclophosphamide- but not IL-10-induced diabetes
      is Fas dependent. Overall, these findings provide evidence that pancreatic
      expression of IL-10 promotes diabetes independent of the major death pathways and
      provide impetus for identification of novel death pathways precipitating
      autoimmune destruction of insulin-producing beta cells.

PMID- 10946318
TI  - Distribution of DNA vaccines determines their immunogenicity after intramuscular
      injection in mice.
AB  - Intramuscular injection of DNA vaccines elicits potent humoral and cellular
      immune responses in mice. However, DNA vaccines are less efficient in larger
      animal models and humans. To gain a better understanding of the factors limiting
      the efficacy of DNA vaccines, we used fluorescence-labeled plasmid DNA in mice to
      1) define the macroscopic and microscopic distribution of DNA after injection
      into the tibialis anterior muscle, 2) characterize cellular uptake and expression
      of DNA in muscle and draining lymph nodes, and 3) determine the effect of
      modifying DNA distribution and cellular uptake by volume changes or
      electroporation on the magnitude of the immune response. Injection of a standard
      50-microl dose resulted in the rapid dispersion of labeled DNA throughout the
      muscle. DNA was internalized within 5 min by muscle cells near the injection site
      and over several hours by cells that were located along muscle fibers and in the
      draining lymph nodes. Histochemical staining and analysis of mRNA expression in
      isolated cells by RT-PCR showed that the transgene was detectably expressed only
      by muscle cells, despite substantial DNA uptake by non-muscle cells. Reduction of
      the injection volume to 5 microl resulted in substantially less uptake and
      expression of DNA by muscle cells, and correspondingly lower immune responses
      against the transgene product. However, expression and immunogenicity were
      restored when the 5-microl injection was followed by electroporation in vivo.
      These findings indicate that distribution and cellular uptake significantly
      affect the immunogenicity of DNA vaccines.

PMID- 10946319
TI  - Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to
      myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced by sensitization with
      myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmune
      disease that reproduces the inflammatory demyelinating pathology of multiple
      sclerosis. We report that an encephalitogenic T cell response to MOG can be
      either induced or alternatively suppressed as a consequence of immunological
      cross-reactivity, or "molecular mimicry" with the extracellular IgV-like domain
      of the milk protein butyrophilin (BTN). In the Dark Agouti rat, active
      immunization with native BTN triggers an inflammatory response in the CNS
      characterized by the formation of scattered meningeal and perivascular
      infiltrates of T cells and macrophages. We demonstrate that this pathology is
      mediated by a MHC class II-restricted T cell response that cross-reacts with the
      MOG peptide sequence 76-87, I GEG KVA LRIQ N (identities underlined). Conversely,
      molecular mimicry with BTN can be exploited to suppress disease activity in MOG
      induced EAE. We demonstrate that not only is EAE mediated by the adoptive
      transfer of MOG74-90 T cell lines markedly ameliorated by i.v. treatment with the
      homologous BTN peptide, BTN74-90, but that this protective effect is also seen in
      actively induced disease following transmucosal (intranasal) administration of
      the peptide. These results identify a mechanism by which the consumption of milk
      products may modulate the pathogenic autoimmune response to MOG.

PMID- 10946320
TI  - Cellular and molecular mechanism for Kilham rat virus-induced autoimmune diabetes
      in DR-BB rats.
AB  - Kilham rat virus (KRV) causes autoimmune diabetes in diabetes-resistant
      BioBreeding (DR-BB) rats; however, the mechanism by which KRV induces autoimmune
      diabetes without the direct infection of beta cells is not well understood. We
      first asked whether molecular mimicry, such as a common epitope between a KRV
      specific peptide and a beta cell autoantigen, is involved in the initiation of
      KRV-induced autoimmune diabetes in DR-BB rats. We found that KRV peptide-specific
      T cells generated in DR-BB rats infected with recombinant vaccinia virus
      expressing KRV-specific structural and nonstructural proteins could not induce
      diabetes, indicating that molecular mimicry is not the mechanism by which KRV
      induces autoimmune diabetes. Alternatively, we asked whether KRV infection of DR
      BB rats could disrupt the finely tuned immune balance and activate autoreactive T
      cells that are cytotoxic to beta cells, resulting in T cell-mediated autoimmune
      diabetes. We found that both Th1-like CD45RC+CD4+ and cytotoxic CD8+ T cells were
      up-regulated, whereas Th2-like CD45RC-CD4+ T cells were down-regulated, and that
      isolated and activated CD45RC+CD4+ and CD8+ T cells from KRV-infected DR-BB rats
      induced autoimmune diabetes in young diabetes-prone BioBreeding (DP-BB) rats. We
      conclude that KRV-induced autoimmune diabetes in DR-BB rats is not due to
      molecular mimicry, but is due to a breakdown of the finely tuned immune balance
      of Th1-like CD45RC+CD4+ and Th2-like CD45RC-CD4+ T cells, resulting in the
      selective activation of beta cell-cytotoxic effector T cells.

PMID- 10946321
TI  - T cells from human allergen-induced late asthmatic responses express IL-12
      receptor beta 2 subunit mRNA and respond to IL-12 in vitro.
AB  - IL-12 suppresses proallergic Th2-type cytokine production and induces Th1-type
      cytokine production by peripheral blood T cells from subjects with allergic
      disease. The objective of the present study was to examine the relevance of these
      findings to target organ T cell responses in human asthma. Bronchoalveolar lavage
      (BAL) and PBMC were collected from atopic asthmatics 24 h after fiberoptic
      allergen challenge of a segmental bronchus. BAL T cells and PBMC were cultured
      with allergen in the presence of recombinant IL-12 or IFN-gamma, and cytokines
      were measured in culture supernatants after 6 days. IL-5 production by BAL T
      cells and PBMC was inhibited by IL-12 and, to a lesser extent, by IFN-gamma. IL
      12 also induced IFN-gamma production by BAL T cells and PBMC. The effects of IL
      12 nor IFN-gamma on IL-5 production could not be reversed by neutralizing anti
      IFN-gamma or anti-IL-12 mAbs, respectively. Thus, the effect of neither IL-12 nor
      IFN-gamma appeared to be mediated through induction of the other cytokine. In
      situ hybridization revealed that approximately one-third of BAL T cells expressed
      mRNA transcripts encoding the IL-12R beta 2 subunit following allergen challenge.
      Thus, human T cells obtained from BAL during asthmatic late responses, like T
      cells in the peripheral circulation, remain susceptible to immunomodulation by IL
      12. These findings raise the possibility that IL-12 may hold therapeutic
      potential in allergic diseases such as asthma.

PMID- 10946322
TI  - Adenoviral-mediated transfer of the TNF-related apoptosis-inducing ligand/Apo-2
      ligand gene induces tumor cell apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily
      of cytokines that induces apoptosis in a variety of cancer cells. The results
      presented in this study demonstrate that introduction of the human TRAIL gene
      into TRAIL-sensitive tumor cells using an adenoviral vector leads to the rapid
      production and expression of TRAIL protein, and subsequent death of the tumor
      cells. Tumor cell death was mediated by an apoptotic mechanism, as evidenced by
      the activation of caspase-8, cleavage of poly(ADP-ribose) polymerase, binding of
      annexin V, and inhibition by caspase inhibitor zVAD-fmk. These results define a
      novel method of using TRAIL as an antitumor therapeutic, and suggest the
      potential use for an adenovirus-encoding TRAIL as a method of gene therapy for
      numerous cancer types in vivo.

PMID- 10946324
TI  - Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells.
AB  - Members of the TNF superfamily, including Fas, Fas ligand, and CD40, have been
      shown to be expressed on tumor cells. In the studies described in this work, we
      report that another family member, the ligand for 4-1BB (CD137), is expressed on
      various human carcinoma cell lines, on cells of solid tumors derived from these
      cell lines, and cells obtained from human tumors. Expression of 4-1BB ligand (4
      1BBL) mRNA was detected by both RT-PCR and Northern blot analysis, and expression
      of 4-1BBL protein was detected by Western blot analysis of whole cell lysates and
      by FACS analysis of tumor cells and cell lines. Incubation of tumor cells with a
      4-1BB-Ig fusion protein led to the production of IL-8 by the cells, demonstrating
      that the 4-1BBL is functionally active and signals back into the tumor cells.
      Furthermore, 4-1BBL expressed on the carcinoma cells functioned as a
      costimulatory molecule for the production of cytokines (most notably IFN-gamma)
      in cocultures of T cells and tumor cells. These findings suggest that 4-1BBL
      expressed on carcinoma cells may significantly influence the outcome of a T cell
      tumor cell interaction.

PMID- 10946325
TI  - The british society for the study of prosthetic dentistry-founded in 1953

PMID- 10946323
TI  - C8/119S mutation of major mite allergen Derf-2 leads to degenerate secondary
      structure and molecular polymerization and induces potent and exclusive Th1 cell
      differentiation.
AB  - Hyposensitization therapy for atopic diseases has been conducted for decades but
      suffered from many problems including anaphylactic reactions. We previously
      developed a mutant protein of the major mite allergen Derf-2, C8/119S, which
      showed reduced binding to IgE. The C8/119S mutant was shown to exhibit more
      efficient hyposensitizing effect than Derf-2 in the animal model of allergic
      bronchial asthma. In the present study, we indicate that C8/119S exhibits
      markedly augmented immunogenicity for the proliferation of Derf-2-specific human
      T cells and T cell clones irrespective of the epitope specificity as compared
      with Derf-2. Furthermore, C8/119S has induced potent and almost exclusive
      differentiation of Th1 cells from the peripheral blood of atopic patients in
      vitro. Neither Ag dosage effect nor absence of B cell-mediated Ag presentation
      could fully account for these effects. C8/119S has been indicated to lose the
      characteristic beta-barrel structure as judged by circular dichroism
      spectroscopic analysis and to polymerize solubly in physiological condition.
      Heating of Derf-2 also caused less stable molecular aggregation, but it hardly
      affected the secondary structure and failed to induce such a polarity toward the
      Th1 cell differentiation. These results have indicated that the degenerate
      secondary structure of C8/119S leading to stable molecular polymerization is
      primarily responsible for the marked increase in T cell-immunogenicity and the
      induction of exclusive Th1 cell differentiation in atopic patients. It has been
      suggested strongly that the recombinant C8/119S protein can provide an effective
      Ag with the least risk of anaphylaxis for allergen immunotherapy against house
      dust mite in human.

PMID- 10946326
TI  - Provisional gold-resin restoration executed through an indirect-direct procedure:
      a clinical report.
AB  - This clinical report describes the treatment of a patient with a procedure that
      solves structural strength problems of conventional acrylic resin prostheses.
      This procedure requires less maintenance and is more resistant to wear. In
      addition, this procedure reduces chair time compared with conventional
      provisional resin restorations

PMID- 10946327
TI  - Tooth-supported telescopic prostheses in compromised dentitions: a clinical
      report.
AB  - This article describes indications for treatment with telescopic restorations on
      patients with periodontally and endodontically compromised dentitions that
      require splinting, with special emphasis on treatment that restores the entire
      dental arch. Stabilization of compromised teeth with fixed splinted restorations
      is usually inadvisable because of the risk factors involved, such as eventual
      localized abutment failure. Detachable telescopic prostheses may be preferred as
      a near equivalent or substitute because they can be detached and repaired without
      reconstruction of the entire restoration. Retentive and splinting properties of
      detachable telescopic restorations can be as effective as FPDs. Inner telescopic
      copings can be cemented as individual crowns to facilitate the procedure.
      Telescopic restorations can be retrieved by the patient for cleaning and easy
      access to the entire marginal periodontal circumference of the abutments. This
      promotes effective home care and oral hygiene. In addition, principles of design
      and indications, as well as technical and clinical factors, were discussed.

PMID- 10946328
TI  - Interdisciplinary treatment of severe maxillofacial trauma: a clinical report.

PMID- 10946329
TI  - Device for recording the path of insertion for removable partial dentures.
AB  - Some negative outcomes of oral rehabilitation using removable partial dentures
      (RPDs) can be prevented when the framework of the RPD is planned with mounted
      diagnostic casts that have been analyzed in a dental surveyor. Recording the
      established path of insertion can be difficult when the procedure uses a pin that
      is cemented in the cast base, and the casts are mounted in an articulator. This
      article presents a procedure for a pin device to record the path of insertion of
      RPDs. This device serves the same purpose as the cemented pin but can be easily
      removed and replaced.

PMID- 10946330
TI  - Changes in marginal gap size of provisional resin crowns after occlusal loading
      and thermal cycling.
AB  - STATEMENT OF PROBLEM: Resin materials used for provisional crowns tend to develop
      enlarged marginal gaps over time. With the advent of new interim resin materials
      in dentistry that are used for longer clinical periods, controlled comparative
      analysis of the structural stability of these materials in the oral environment
      is required. PURPOSE: This study analyzed marginal gap size changes resulting
      from occlusal loading and thermal cycling and related these results to material
      properties. MATERIAL AND METHODS: Groups (n = 10) of provisional crowns were made
      using 4 resin materials (Jet-relined, Snap-relined, Snap-unrelined, Alike
      unrelined). Specimens were first fabricated on a metal master die and fitted with
      and relined on the master die to standardize pretreatment marginal gap size.
      Custom die stems were fabricated from a low-fusing alloy (Cerroblend) and
      cemented with Tempbond cement. The samples were treated with occlusal loading
      (50,000 cycles, 40 N, 4 Hz) and thermocycling (8, 000 cycles, 5 degrees C to 60
      degrees C). Measurements of marginal gaps were recorded before and after
      treatment. RESULTS: The mean changes in marginal gap sizes were Jet-relined,
      152.1 microm +/- 69. 6; Snap-relined, 548.9 microm +/- 168.3; Snap-unrelined,
      446.6 microm +/- 91.8; and Alike-unrelined, 43.9 microm +/- 48.7. Two-way ANOVA
      revealed a significant difference between groups (F=51.758, df 3,1, P</=.0001).
      Tukey/Kramer (P </=.01 level) indicated a significantly larger gap increase for
      the Snap-relined and Snap unrelined groups. CONCLUSION: There were significant
      differences between different brands of resin materials used for provisional
      crowns. Each must be evaluated individually for stability in the oral
      environment.

PMID- 10946331
TI  - Strengths of composite bonded to base metal alloy using dentin bonding systems.
AB  - STATEMENT OF PROBLEM: Many different bonding systems are currently available that
      may be used to bond composite to base metal alloy. PURPOSE: This study measured
      and compared bond strengths of composite with a base metal alloy using 8 modern
      dentin bonding systems. MATERIAL AND METHODS: Base metal alloy buttons were
      imbedded in acrylic and ground with 120, 400, and 600 grit sandpaper,
      respectively. Metal surfaces were air abraded for 5 seconds with 50 microm
      aluminum oxide, washed for 5 seconds under running tap water, then dried with
      compressed air. Specimens were arbitrarily divided into 8 groups of 10 specimens.
      Each group was treated with 1 of 8 dentin bonding regimens. A hybrid composite
      (Herculite) was placed onto the treated metal surface and light polymerized.
      Specimens were incubated at 37 degrees C in distilled water for 2 hours. Shear
      bond strengths were measured and the collected data subjected to an ANOVA,
      followed by multiple t -tests. RESULTS: All-Bond 2 exhibited the highest mean
      shear bond strength and Panavia 21 with primer had the lowest in the tests
      conducted. CONCLUSION: All-Bond 2 demonstrated significantly higher shear bond
      strengths over all materials tested, except 3M Single Bond and Optibond FL. No
      significant difference was noted between the single component and the
      multicomponent bonding systems.

PMID- 10946332
TI  - Computer modeling of occlusal surfaces of posterior teeth with the CICERO CAD/CAM
      system.
AB  - STATEMENT OF PROBLEM: Static and dynamic occlusal interference frequently needs
      to be corrected by selective grinding of the occlusal surface of conventional
      cast and ceramic-fused-to-metal restorations. CAD/CAM techniques allow control of
      the dimensional contours of these restorations. However, parameters responsible
      for the occlusal form need to be determined. In most articulators, these
      parameters are set as default values. Which technique is best for minimizing the
      introduction of occlusal interference in restorations has not been determined.
      PURPOSE: This study investigated differences in crown structure of a crown
      designed in static occlusion (STA) with designs adapted for dynamic occlusal
      interferences. Therefore, values from an optoelectronic registration system
      (String-Condylocomp, KAVO), an occlusal generated path (OGP) technique and
      default settings (DEF) were used in the CICERO CAD/CAM system. MATERIAL AND
      METHODS: Morphology of CON, DEF, and OGP crowns was compared with that of the STA
      crown with respect to differences in a buccolingual section and frequency of
      occlusal distances in an interocclusal range of 1 mm, measured from the occlusal
      surface of the crown. RESULTS: All crown types fulfilled the esthetic and
      morphologic criteria for restorations in clinical dentistry. Difference in the
      morphology of the OGP crown, compared with that of the STA crown, was greater
      than that for the CON and DEF crowns. These differences were seen especially in
      the distobuccal part of the occlusal surface; however, the number of occlusal
      contacts was considered sufficient to stabilize occlusion. CONCLUSION: Functional
      occlusion, adapted to dynamic occlusion in a CICERO crown for the first
      mandibular molar, can be obtained using data acquired with the String-Condylocomp
      registration system. The OGP technique was preferred to other techniques because
      of the simplicity of the technique for eliminating potential problems with
      opposing teeth during motion. However, this is achieved at the cost of fewer
      points of contact during occlusion than with the CON crown.

PMID- 10946333
TI  - Clinical evaluation of allografts and homografts for restoration of missing tooth
      structure.
AB  - STATEMENT OF PROBLEM: The clinical performance of bonding human tooth fragments
      to either replace missing teeth or to restore defective teeth is unclear.
      Prospective studies can help to predict the success of such treatment options.
      PURPOSE: This study evaluated the feasibility of bonding tooth tissue homografts
      and allografts either to replace missing teeth or to restore defective teeth, and
      estimated the success rate of bonded allograft and homograft restorations 3 years
      after placement. METHOD AND MATERIAL: Twenty clinical cases were treated by
      bonding tooth fragments or crowns into 6 groups (Gp): Gp1, cervical erosion and
      abrasion lesions (6); Gp2, incisal edge fractures (4); Gp3, partially destroyed
      crowns (4); Gp4, teeth placed in a removable prosthesis (2); Gp5, missing tooth
      with no opposing tooth (2); and Gp6, temporary space maintenance (2).
      Restorations were examined using USPHS criteria every 2 months and whenever a
      patient called to report a failure. RESULTS: After a 3-year follow-up, the
      overall success rate was 80% for the 20 restorations. The 95% confidence interval
      was 63% to 94%. Four restorations failed by debonding (Gp2 [2]; Gp5 [1]; Gp6 [1])
      during the first 4 months. The main cause of failure appeared to be excessive
      occlusal loading. CONCLUSION: Within the limitations of this clinical study, the
      results after a 3-year follow-up showed the success rate was not less than 63%
      for bonded allograft and homograft restorations.

PMID- 10946334
TI  - Effect of crown lengthening and ferrule placement on static load failure of
      cemented cast post-cores and crowns.
AB  - STATEMENT OF PROBLEM: Restoration of mandibular second premolars with completely
      missing clinical crowns in the Kennedy Class I and II arches is costly and the
      risk of failure is high. Should the dentist choose crown-lengthening to allow the
      addition of a ferrule, despite incurring the disadvantage of an increased
      crown/root ratio? PURPOSE: This in vitro study determined the combined effect of
      crown lengthening and placement of a ferrule on the failure resistance to static
      load of decoronated and restored mandibular second premolar analog teeth.
      MATERIAL AND METHODS: An extracted mandibular second premolar of average
      dimensions was selected to form molded composite root analogs and metal crowns.
      Ten specimens prepared with no-ferrule root and negligible axial wall lengths and
      10 specimens with ferrule root, apically repositioned finish lines, were made.
      Cast gold alloy post and cores and complete crowns were made and cemented. Each
      root was placed in bone-simulating resin located 3 mm from the finish line. Crown
      lengthened/ferrule and no-crown lengthened/no-ferrule groups were equally
      subdivided, whereby 5 crowns were compressively loaded on the buccal cusp tip and
      5 were compressively loaded on the mesial marginal ridge. A testing machine
      applied force until failure occurred. Failure loads were examined with 2-way
      ANOVA. Significant differences were accepted at P </=.05. RESULTS: Mean failure
      loads for the crown lengthened/ferrule and no-crown lengthened/no-ferrule groups
      were as follows: buccal load, 0.61 kN (SD +/- 0.11) and 0.83 kN (SD +/- 0.08);
      mesial load, 0.70 kN (SD +/- 0.08) and 1.00 kN (SD +/- 0.15), respectively. Crown
      lengthened/ferrule and no-crown lengthened/no-ferrule groups were significantly
      different (P <.001). CONCLUSION: The combination of simulated surgical crown
      lengthening and more apical crown margin placement to provide a 2-mm crown
      ferrule on a decoronated mandibular second premolar analog resulted in a
      reduction of static load failure for the restored analog tooth.

PMID- 10946335
TI  - Influence of post placement in the fracture resistance of endodontically treated
      incisors veneered with direct composite.
AB  - STATEMENT OF PROBLEM: Veneer preparations are considered to weaken endodontically
      treated maxillary incisors. Prefabricated posts have been controversially
      indicated to reinforce endodontically treated teeth before final restoration.
      PURPOSE: This in vitro study evaluated whether (1) veneer preparation in enamel
      or in enamel/dentin weakens endodontically treated maxillary incisors, (2)
      bonding of direct composite veneer restores the original strength of the
      unprepared teeth, and (3) use of prefabricated metal posts increases fracture
      resistance of prepared and restored teeth. MATERIAL AND METHODS: Ninety extracted
      human maxillary central incisors were submitted to conventional root canal
      treatment. Specimens were randomly divided into 8 experimental groups (veneer
      preparation in enamel or dentin with/without post and with/without direct
      composite veneer restoration) and a control group (n = 10). Specimens were loaded
      to fracture, and the data were analyzed statistically. RESULTS: Statistical
      analysis revealed that a conservative veneer preparation does not significantly
      reduce maxillary incisors' fracture resistance. For prepared incisors, bonding of
      direct composite veneer restored their original strength, and the use of posts
      did not increase their fracture resistance. CONCLUSION: Conservative veneer
      preparations involving enamel and enamel/dentin did not significantly reduce the
      fracture resistance of endodontically treated maxillary incisors. In addition,
      restoration of the intraenamel preparations with direct composite resulted in
      teeth more resistant to fracture than teeth having restorations in dentin. The
      use of posts did not improve fracture resistance of endodontically treated
      maxillary incisors reduced and veneered with direct composite.

PMID- 10946336
TI  - Effect of osseointegrated implants on the coordination of masticatory muscles: a
      pilot study.
AB  - STATEMENT OF PROBLEM: The neuromuscular network of masticatory function is, in
      part, coordinated with afferent information provided by the periodontal ligament
      (PDL). Osseointegrated implant-supported prostheses lack this PDL-derived
      proprioceptive feedback mechanism. PURPOSE: This pilot study was designed to
      address the hypothesis that implant patients acquire different patterns of
      functional coordination. Patients with implant-supported prostheses were
      characterized in regard to masticatory muscle tenderness and fatigue as well as
      changes in the coordinated activities of masticatory muscles during chewing and
      maximal occluding force. Results were compared with those of patients with
      natural teeth and interpreted to assess the functional outcome of implant
      therapy. MATERIAL AND METHODS: Fifty-seven volunteers (25 partially edentulous
      patients restored with implantsupported fixed prostheses; 32 control patients)
      were evaluated. A comprehensive set of clinical examinations was performed,
      including occlusal analysis and examination of masticatory muscle and TMJ. EMG
      recordings of 5 volunteers from each group were further evaluated. EMG activities
      of the masseter and anterior temporalis were recorded during habitual chewing and
      voluntary maximal occluding force. RESULTS: There were essentially no differences
      in the clinical evaluations between volunteers in the implant and control groups
      and no significant alterations in the masticatory muscle coordination for
      habitual chewing. During the maximal occluding force measurement, EMG recordings
      revealed a unique masticatory muscle coordination pattern in the implant group
      with a tendency to activate the working and nonworking side muscles
      simultaneously. CONCLUSION: Patients with implant-supported prostheses appeared
      to be well adapted to perform habitual masticatory functions. However, during a
      nonhabitual function such as maximal occluding force, our pilot data revealed a
      less coordinated masticatory muscle activity in the implant patients.

PMID- 10946337
TI  - Effect of repeated closures on opening torque values in seven abutment-implant
      systems.
AB  - STATEMENT OF PROBLEM: Implant abutment screw joints tend to loosen under clinical
      conditions. During impression and prosthesis fabrication, repeated clinical
      closing and opening of abutment screws may cause component wear and decrease
      frictional fit of the mating parts, resulting in altered resistance to opening
      and potential for loss of preload in function. PURPOSE: This study recorded
      changes in opening torque values due to multiple consecutive closures at a
      constant torque within and between different abutment/implant (A/I) systems.
      MATERIAL AND METHODS: Repeated opening-closing cycles were used to simulate in
      vitro embedment relaxation and component wear of 7 A/I systems from 5
      manufacturers. Screw opening torque values were recorded up to 200 consecutive
      closures at 20 N/cm. RESULTS: A progressive decrease in opening torque values was
      measured in all implant systems. Significant differences were found between A/I
      systems. Systems with morse tapered and spline connections consistently
      maintained a higher resistance to opening force. Percentage torque loss ranged
      from 3% to 20% on immediate opening, and from 4.5% to 36% for average of first 30
      opening/closing cycles. CONCLUSION: Repeated opening and closing of implant
      abutment screws caused progressive loss of torque retention with variations
      between systems. This was probably due to a decrease in the coefficient of
      friction between the mating components.

PMID- 10946338
TI  - Fiber-reinforced composite framework for implant-supported overdentures.
AB  - This article presents a new method for fabricating a framework for an implant
      supported overdenture using unidirectional fiber-reinforced composite. This
      procedure eliminates the need for a traditional metal alloy framework. The fiber
      reinforced composite framework has the advantages of lower cost, less time and
      materials needed during fabrication, minimal potential for toxicity to the
      technician and patient, and a more esthetic metal-free final result.

PMID- 10946339
TI  - Fabrication of a two-piece superstructure for a fixed detachable implant
      supported mandibular complete denture.
AB  - This article describes a procedure to fabricate a 2-piece superstructure for a
      fixed detachable implant-supported mandibular complete denture prosthesis. With
      this unique technique, unsuitable implant angulation can be corrected, and
      retention of the second superstructure is accomplished with 2 esthetically
      positioned screws and an antirotational attachment.

PMID- 10946340
TI  - Guidelines for splinting implants.
AB  - STATEMENT OF PROBLEM: Teeth and implants have different mobility patterns. Thus,
      it has been believed that implant-supported restorations should not be connected
      to natural teeth. However, this is not always the case. PURPOSE: This article
      presents guidelines for connection of restorative components when implant
      abutments and natural teeth are involved. METHODS: Methods of connection are
      discussed. CONCLUSION: This article presents options for splinting of prosthetic
      components.

PMID- 10946341
TI  - Peri-implant skin graft for a craniofacial prosthesis.

PMID- 10946342
TI  - New method for the in vitro evaluation of dental alloy bonding systems.
AB  - STATEMENT OF PROBLEM: Bonding systems are used in some fixed prosthetic devices
      with base alloys. However, different studies of the same dental alloy bonding
      agents, under similar circumstances, have yielded disparate results in bond
      strength testing. PURPOSE: This study compared directly 2 dental alloy bonding
      systems through a "duel" type of confrontation, which basically is a 2-way
      tensile force test. MATERIAL AND METHODS: Ninety Wiron 88 base alloy cylinders
      (diameter of 8 mm length 15 mm) were sandblasted on both sides with Al(2)0(3)
      powder (particle size 50 microm) during 10 seconds at an approximate distance of
      5 mm, at an air pressure of 60 psi determined before sandblasting procedures. The
      surface of each cylinder was cleaned from Al(2)0(3) powder with a strong burst of
      oil-free air from a chairside air syringe. Thirty cylinders were randomly
      assigned to 1 of 3 groups for direct bond strength comparison: (1) Panavia 21 to
      Panavia EX, (2) Panavia 21 to Metabond, or (3) Panavia 21 to a combination of a
      resin bonding agent plus Panavia 21. Each group was composed of 10 specimens that
      used 3 cylinders for each specimen. Each side of the sample cylinder received the
      same quantity of cement and 1 cylinder at a time was bonded to it. Cylinder
      alignment was verified with a Boley gauge during luting procedures. The bonded 3
      piece block was held together for 24 hours under a compressive force of 2
      kg/cm(2) using a hydraulic press. Excess cement was removed with a brush, and the
      pertinent air sealant was applied to allow for autocuring of the cement.
      Specimens were later stored in water at room temperature for 48 hours before
      thermocycling procedures. Each specimen was thermocycled for 100 cycles with a 5
      minute dwelling time in water at 4 degrees C and 60 degrees C. Specimens were
      subject to tensile force testing until debonding in 1 of the cylinders. RESULTS:
      The opposing pull duel test (OPDT) showed that the Panavia EX failed (40. 3 MPa)
      10 of 10 duels against Panavia 21, whereas Panavia 21 failed (49.7 MPa) 9 of 10
      duels against Metabond, and Panavia 1 failed (50. 1 MPa) 10 of 10 duels against
      Photobond+Panavia 21. ANOVA revealed significant differences (P <.05) between PAN
      EX group and MET and PHB+P21 groups. However, no significant differences were
      found between MET and PHB+P21 groups. CONCLUSION: The opposing pull duel test was
      a valid method to directly compare bond strengths of 2 bonding systems to dental
      base alloys. There was a small dispersion of the values even though cement mixing
      and thickness variables were difficult to control. Duel tensile testing provides
      meaningful information on the superiority of one bonding system over another in
      this controlled environment.

PMID- 10946343
TI  - Effect of water temperature during polymerization on strength of autopolymerizing
      resin.
AB  - STATEMENT OF PROBLEM: Breakage is a potential problem of provisional resin
      restorations. A method that effectively increases the strength of the resin is
      desirable. PURPOSE: This study examined the effects of the curing environment,
      air or water, and water temperature during polymerization on the mechanical
      properties of autopolymerizing resin. MATERIAL AND METHODS: After mixing the
      autopolymerizing methyl methacrylate resin for 10 seconds, it was placed in a
      stainless steel mold (2 x 2 x 25 mm). One minute and 50 seconds after the start
      of mixing, the mold containing the resin was placed under the following
      conditions: in air at 23 degrees C; or in water at 10 degrees C, 23 degrees C, 30
      degrees C, 40 degrees C, 60 degrees C, and 80 degrees C. Six minutes after mixing
      began, the resin specimen was removed from the mold and the transverse test (3
      point flexural test) was performed. RESULTS: Alteration of conditions during
      polymerization revealed a significant effect on both the transverse strength and
      modulus of the resin (P <.0001). Both increased with an increase in water
      temperature. Water conditions of 60 degrees C to 80 degrees C produced more than
      2 times greater transverse strength and modulus of the resin compared with
      polymerization in 23 degrees C air (P <.0001). CONCLUSION: Polymerization of the
      resin in hot water greatly increased its mechanical properties. The method of
      placing resin restorations in hot water during polymerization may be useful for
      improving mechanical requirements and obtaining long-lasting performance.

PMID- 10946344
TI  - Effectiveness of two devices designed to prevent fluid retraction in a high-speed
      handpiece.
AB  - STATEMENT OF PROBLEM: Contaminated fluid can be retracted into the turbine air
      chamber of a high-speed handpiece when it stops rotating. PURPOSE: This study
      attempted to evaluate 2 operating systems recently equipped with antiretraction
      devices installed inside the handpiece (Kavo) or inside the unit (Castellini) and
      to compare the results with those obtained from an operating system without any
      antisuction device (Bien Air). MATERIAL AND METHODS: Two test conditions (bur
      immersed approximately 5 mm into a dye solution or completely immersed in dye
      solution) were conducted using potassium bichromate dye to simulate a fluid
      contaminant. RESULTS: During the first procedure dye influx for the Kavo unit was
      0.08 +/- 0.1 microL, 0.06 +/- 0.1 microL for the Castellini unit, and 12.4 +/-
      5.2 microL for the Bien Air unit (F=28.3; P <.01). During the second procedure,
      the results of the dye influx were Kavo unit 2.52 +/- 1.3 microL, Castellini unit
      0.1 +/- 0.1 microL, and Bien Air unit 22.22 +/- 4.0 microL (F=123; P <.01). Mean
      values were significantly different between Castellini and Kavo units during the
      second procedure. CONCLUSION: Antisuction devices can reduce dye penetration into
      the air chamber of a high-speed handpiece. Better results may be obtained with
      devices installed inside the unit and designed to increase the air pressure in
      the air chamber when the turbine stops running.

PMID- 10946345
TI  - Cytotoxicity of dental alloys, metals, and ceramics assessed by millipore filter,
      agar overlay, and MTT tests.
AB  - STATEMENT OF PROBLEM: Biocompatibility of dental materials is dependent on the
      release of elements from the materials. In addition, the composition,
      pretreatment, and handling of the materials influence the element release.
      PURPOSE: This study evaluated the cytotoxicity of dental alloys, metals, and
      ceramics, with specific emphasis on the effects of altering the composition and
      the pretreatment. MATERIAL AND METHODS: By using cells from a mouse fibroblast
      cell line and the agar overlay test, Millipore filter test, and MTT test,
      cytotoxicity of various metals, metal alloys, and ceramics for dental restoration
      were studied. Effects of altering the composition of a high noble gold alloy and
      of pretreatment of a ceramic-bonding alloy were also studied. In addition, the
      release of elements into the cell culture medium by the materials studied was
      measured using an inductively coupled plasma optical emission spectrophotometer.
      The results of the MTT test were analyzed statistically using ANOVA and Scheffe
      test at a significance level of P <.05. RESULTS: Specimens manufactured from
      materials intended for dental restorations and handled in accordance with the
      manufacturers' instructions were ranked from "noncytotoxic" to "mildly cytotoxic"
      according to the agar overlay and Millipore filter tests. For the MTT test, no
      significant differences were observed between these materials and controls, with
      the exception of JS C-gold and unalloyed titanium. The modified materials were
      ranked from "mildly cytotoxic" to "moderately cytotoxic" in the agar overlay and
      Millipore filter tests and from "noncytotoxic" to "moderately cytotoxic" in the
      MTT test. Thus, cytotoxicity was related to the alloy composition and treatment.
      The release of Cu and Zn seemed to be important for the cytotoxic effect.
      CONCLUSION: Alterations in the composition and the pretreatment can greatly
      influence the cytotoxicity, and the results stress the importance of carefully
      following the manufacturers' instructions when handling dental materials.

PMID- 10946346
TI  - Modified custom tray.
AB  - The use of a custom tray is highly desirable for accurate impression making in
      situations with multiple abutments. This article describes a modified custom tray
      fabrication method using autopolymerizing acrylic resin. The custom tray is
      fabricated by intraoral relining with autopolymerizing resin that is polymerized
      extraorally. The final impression is obtained during the same session after tray
      polymerization at 100 degrees C for 5 minutes. Relined areas are refined by
      trimming excess resin with burs of a known diameter to create a 2-mm clearance
      for the elastomer. For areas with subgingival finish lines, only 0.5 mm of resin
      is removed to direct the elastomer into the gingival sulcus. The procedure is
      time-saving because it reduces the need for a retraction cord and minimizes
      inaccuracies that would necessitate another impression.

PMID- 10946347
TI  - Impression procedure for patients with severely limited mouth opening.
AB  - Patients with limited mouth opening are a common occurrence in prosthodontic
      practice. The majority of these patients can be treated with exercise and
      stretching movements before impressions are made. Some will not respond to these
      procedures because of facial scarring and surgical manipulation of the facial
      muscles. This article presents an impression procedure for overcoming such
      reduced mouth opening.

PMID- 10946348
TI  - Stabilization of measuring device during range of motion evaluation.

PMID- 10946350
TI  - Familial congenital pulmonary lymphangectasia, non-immune hydrops fetalis, facial
      and lower limb lymphedema: confirmation of Njolstad's report.
AB  - We report on four cases, three familial and one sporadic, with congenital
      pulmonary lymphangectasia and facial and lower limb lymphedema. Hydrops fetalis
      was observed in three cases and death occurred in one of those. This is the third
      report describing inherited pulmonary lymphangectasia with a clinical phenotype
      very similar to that described by Njolstad et al. [1998: Eur J Pediatr 157: 498
      501], who reported three sibs with non-immune hydrops fetalis (NIHF),
      chylothorax, pulmonary lymphangectasia, distal lymphedema, and swelling of the
      face. We think that the present report and that of Njolstad et al. describe a new
      condition very similar to Hennekam syndrome, which is characterized by autosomal
      recessive inheritance, intestinal lymphangiectasia, lymphedema of the lower limbs
      and facial anomalies (flat face, hypertelorism, flat, broad nasal bridge,
      lymphedema, tooth anomalies, and ear defects). Similarity with our cases and
      Hennekam syndrome will be discussed.

PMID- 10946349
TI  - Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of
      hereditary breast and ovarian cancer families.
AB  - Although BRCA1/2 testing has increasingly entered clinical practice, much is to
      be learned about the most effective ways to provide counseling to persons
      potentially interested in receiving test results. The purpose of this study was
      to identify factors affecting genetic testing decisions in a cohort of hereditary
      breast and ovarian cancer (HBOC) families presented with the choice to undergo
      testing. Relatives in these families are known to carry BRCA1 or BRCA2 mutations.
      Sociodemographics, personality traits, and family functioning were self-assessed
      using validated psychometric instruments at baseline. Among 172 individuals who
      participated in pretest education and counseling, 135 (78%) chose to undergo
      genetic testing and 37 (22%) chose not to be tested. Individuals who chose to
      undergo genetic testing were more likely to be older (> or =40 years), to have
      lower levels of optimism, and to report higher levels of cohesiveness in their
      families. A better understanding of factors that influence interest in predictive
      testing may help to inform the counseling that occurs prior to genetic testing.

PMID- 10946351
TI  - Magnetic resonance findings and ophthalmologic abnormalities are correlated in
      patients with neurofibromatosis type 1 (NF1).
AB  - In subjects with neurofibromatosis type 1 (NF1), we show that a reduction in the
      visual field is the most sensitive indicator of gliomas along the optic pathway.
      Therefore, we conclude that a visual field evaluation is the most sensitive
      clinical test among those evaluated to predict the presence of optic pathway
      pathology on an MRI examination. These data may contribute to the establishment
      of more precise guidelines for the evaluation and treatment of children with NF1.

PMID- 10946352
TI  - Familial cryptic (20;21) translocation identified by in situ hybridization
      technologies.
AB  - We report on a familial cryptic (20;21) translocation [(t20;21)] that was
      initially suspected with the observation of a single chromosome 21 specific
      signal in an interphase nuclei by in situ hybridization (FISH) study performed on
      a 34-week gestation amniotic fluid specimen. The genetic amniocentesis was
      prompted by the presence of fetal anomalies detected by ultrasound. In addition,
      there was a family history of a maternal uncle with mental retardation and
      multiple malformations and an apparently normal karyotype. No obvious aberration
      could be detected in the G-banded karyotype prepared from the amniotic fluid
      specimen. A FISH study using a chromosome 21 specific long arm probe and
      chromosome 20 whole chromosome paint, however, showed an unbalanced rearrangement
      in the fetus [46,XY, der(21)t(20;21)(q13.2;q22.13 or 22.2) mat]. The mother and
      maternal grandmother were demonstrated to be balanced translocation carriers.
      These results were confirmed by multicolor karyotyping. This familial aberration
      was discovered by chance in the interphase FISH analysis. Our experience with
      this case, however, serves to emphasize the importance of the reevaluation of
      patients with mental retardation and congenital malformations of unknown cause
      and prudent use of multicolor karyotyping in the detection of cryptic cytogenetic
      rearrangements.

PMID- 10946353
TI  - Mutational analysis of RET/GDNF/NTN genes in children with total colonic
      aganglionosis with small bowel involvement.
AB  - Hirschsprung disease (HSCR) is characterized by the absence of intramural
      ganglion cells in the distal gut, resulting in bowel obstruction shortly after
      birth. Aganglionosis usually affects the distal colon, but may also extensively
      involve the entire colon and, rarely, the more proximal bowel. Recently, germline
      mutations of RET, GDNF, and NTN genes have been reported in HSCR. Here we
      describe the results of mutational analysis of these genes in 15 Japanese child
      patients with total colonic aganglionosis with small bowel involvement. DNA
      sequences of all the RET/GDNF/NTN coding regions were determined by the direct
      dyedeoxy terminator cycle method. Eight different RET mutations were identified
      in exons 1, 7, 10, 12, 15, and 17 in 10 of the 15 patients. Of these eight
      mutations, five were found in the tyrosine kinase domain. No GDNF or NTN mutation
      was found. Compared with typical HSCR, this patient group appeared to exhibit a
      higher percentage of RET mutations and accumulation of mutations in the tyrosine
      kinase domain. A homozygous (or hemizygous) RET mutation was found in a male baby
      with total intestinal aganglionosis, while the heterozygosity of the same
      mutation resulted in a less severe type of aganglionosis. In familial cases, all
      heterozygous for the same mutation, aganglionosis was more severe in male than in
      female siblings. These results also urge us to examine if the RET germline
      mutation may cause critical alteration of the GDNF/NTN-Ret signal transduction
      more severely in homo(hemi)zygosity and in male fetuses during organogenesis.

PMID- 10946354
TI  - Wolf-Hirschorn syndrome resulting from partial monosomy 4p/trisomy 9p.
AB  - An infant girl was referred for a genetic consultation because of facial
      appearance suggestive of Wolf-Hirschorn syndrome (WHS), growth retardation and
      generalized hypotonia. She had an unbalanced karyotype
      46,XX,der(4)t(4;9)(p15.2;p22)mat resulting in the deletion of the critical region
      for WHS and duplication of the critical region for the 9p duplication syndrome.
      The mother and the grandmother of proposita were the carriers of an apparently
      balanced translocation 46,XX,t(4;9)(p15.2;p22). The infant's phenotype was
      characteristic of WHS syndrome rather than that of duplication 9p phenotype. This
      is probably the first description of WHS phenotype resulting from a familial 4;9
      translocation.

PMID- 10946355
TI  - Mapping of a gene for nonspecific X-linked mental retardation (MRX 75) to Xq24
      q26.
AB  - Nonspecific X-linked mental retardation is a heterogeneous condition consisting
      of nonsyndromal mental retardation in males. It is caused by mutation in one of
      several genes on the X chromosome (MRX genes). Here we report on the localization
      of a presumptive MRX gene to chromosomal region Xq24-q26 in a German family with
      nonspecific X-linked mental retardation (MRX 75, HUGO Human Gene Nomenclature
      Committee). Two point linkage analysis with 23 informative markers gave a lod
      score of 2.53 at theta = 0 for markers DXS425, DXS1254, DXS1114, and HPRT.

PMID- 10946356
TI  - Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation.
AB  - X-linked mental retardation is a very common condition that affects approximately
      1 in 600 males. Despite recent progress, in most cases the molecular defects
      underlying this disorder remain unknown. Recently, a study using the candidate
      gene approach demonstrated the presence of mutations in PAK3 (p21-activating
      kinase) associated with nonspecific mental retardation. PAK3 is a member of the
      larger family of PAK genes. PAK proteins have been implicated as critical
      downstream effectors that link Rho-GTPases to the actin cytoskeleton and to MAP
      kinase cascades, including the c-Jun amino-terminal kinase (JNK) and p38. We
      screened 12 MRX pedigrees that map to a large region overlying Xq21-q24. Mutation
      screening of the whole coding region of the PAK3 gene was performed by using a
      combination of denaturing gradient gel electrophoresis and direct sequencing. We
      have identified a novel missense mutation in exon 2 of PAK3 gene (R67C) in MRX47.
      This confirms the involvement of PAK3 in MRX following the report of a nonsense
      mutation recently reported in MRX30. In the MRX47 family, all affected males show
      moderate to severe mental retardation. No seizures, statural growth deficiency,
      or minor facial or other abnormal physical features were observed. This mutation
      R67C is located in a conserved polybasic domain (AA 66-68) of the protein that is
      predicted to play a major role in the GTPases binding and stimulation of Pak
      activity.

PMID- 10946357
TI  - Human CD36 deficiency is associated with elevation in low-density lipoprotein
      cholesterol.
AB  - To find out whether CD36 plays a role in the human lipoprotein metabolism, we
      studied lipoprotein profiles in subjects with CD36 deficiency. Apparently healthy
      Japanese volunteers (n = 790) were classified by flow cytometry into three groups
      of normal (platelet and monocyte CD36+, n = 741, 93.8%), type-II deficiency
      (platelet CD36- and monocyte CD36+, n = 45, 5.7%), and type-I deficiency
      (platelet and monocyte CD36-, n = 4, 0.5%). At least one of reported mutations in
      the CD36 gene was found in all four subjects with type-I deficiency and in 23 of
      the 45 subjects with type II. Among 779 subjects (731 normals, 44 type II, and
      four type I) with serum triglyceride levels of <400 mg/dL, serum total
      cholesterol and low-density lipoprotein (LDL) cholesterol were significantly
      elevated in type-II deficiency (P = 0.0095 and 0.0382 versus normal,
      respectively, Scheffe's F-test), while differences were not significant in
      triglyceride and high-density lipoprotein-cholesterol. Similar tendency was
      observed in type-I deficiency, although the differences were not statistically
      significant because of small sample size. We conclude that CD36 deficiency
      elevates LDL cholesterol, indicating a contribution of CD36 to LDL metabolism.

PMID- 10946358
TI  - Tandem duplication/deletion in a maternally derived chromosome 9 supernumerary
      derivative resulting in 9p trisomy and partial 9q tetrasomy.
AB  - A 19-week stillborn female fetus with bilateral cleft palate, horseshoe kidney,
      bicornuate uterus, low-set ears, and intrauterine growth retardation (IUGR) was
      found to have a supernumerary derivative chromosome 9 (der(9)) with an apparent
      tandem duplication in the long arm. PCR analysis at five polymorphic loci
      confirmed the duplication and showed an adjacent deletion, while whole chromosome
      FISH demonstrated only chromosome 9 to be involved. Further FISH studies of
      der(9) found the 9qh region to be duplicated, telomeric sequences to be intact,
      and subtelomeric sequences to be absent. Thus, the fetus was determined to be
      trisomic for 9pter-->9q12 and 9q34.3-->9qter, tetrasomic for 9q12--> 9q33, and
      disomic for 9q33-->9q34.3. These results are consistent with a tandem duplication
      of 9q12-->9q33 and adjacent distal deletion as designated by the karyotype,
      47,XX,+der(9)dup(9) (q12q33)del(9) (q33q34.3).ish der(9)(WCP9+,D9Z1x2,STP9q-,
      AHT+) de novo. In addition to characterizing der(9), the combined PCR and
      cytogenetic studies refined the Genome Database Map of three loci (D9S907,
      D9S155, and D9S302) approximately to the distal 9q33 region. Without the attempt
      to refine breakpoints by PCR analysis, the deletion in distal 9q would not have
      been detected. Tandem direct duplication/deletion chromosomes have been reported
      in fewer cases than inverted duplication/deletions. We propose mechanisms of
      origin, consistent with those for recurrent inter stitial microdeletion and
      microduplication syndromes, shown to arise by recombination at homologous,
      flanking DNA sequences.

PMID- 10946359
TI  - Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the
      clinical and biochemical phenotype.
AB  - Ornithine transcarbamylase (OTC) deficiency, a partially dominant X-linked
      disorder, is the most common inherited defect of the urea cycle. Previous reports
      suggested a variable phenotypic spectrum, and several studies documented
      different "private" mutations in the OTC genes of patients. Our laboratory
      identified disease-causing mutations in 157 families with OTC deficiency, 100 of
      which came to medical attention through a hemizygous propositus and in 57 the
      index case was a heterozygous female. We correlated the genotype with age of
      onset, liver OTC activity, incorporation of nitrogen into urea, and peak plasma
      ammonia levels. The "neonatal onset" group has a homogeneous clinical and
      biochemical phenotype, whereas the "late onset" group shows an extremely wide
      phenotype; 60% of the mutations are associated exclusively with acute neonatal
      hyperammonemic coma. The remaining mutations caused a nonuniform phenotype
      ranging from severe disease to no symptoms; 31% of the mutations in the OTC gene
      occur in CpG dinucleotides (methylation-mediated deamination), and none of them
      accounted for more than 4% of the total. Eighty-six percent of the mutations
      represented single-base substitutions and 68% of the substitutions were
      transitions. G-to-A and C-to-T transitions were the most frequent substitutions
      (34 and 21%, respectively) whereas C-to-A, A-to-C, C-to-G, and T-to-A
      transversions were the least common (1.5-3%). Twenty percent of propositi and 77%
      of propositae carried new mutations. Forty percent of female germinal mutations
      were in CpG dinucleotides whereas this number appears much smaller in male
      germinal mutations. These data allow classification of patients with OTC
      deficiency into at least two groups who have discordant disease course and
      prognoses. In addition, they improve our understanding on the origin of mutations
      in the OTC gene and allow better counseling of affected families.

PMID- 10946360
TI  - Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT)
      type 2 kindred.
AB  - HHT type 2 (HHT 2) is a multi-system vascular dysplasia caused by a mutation in
      the ALK-1 gene, but the phenotype has not been well defined. We report on 51
      members of an HHT 2 kindred with an ALK-1 gene mutation shown to be associated
      with the disorder. This ALK-1 mutation was detected in 38 kindred members who
      were evaluated systematically for associated vascular abnormalities. Pulmonary
      arteriovenous malformations (AVMs) were found in 6% of those screened, cerebral
      AVM in 7%, hepatic AVM in 17%, and spinal AVM in 3%. We discuss these and other
      findings in the 38 affected kindred members, as well as findings in the 13
      kindred members in whom the mutation was not detected. This study shows that
      pulmonary, cerebral, spinal, and hepatic AVMs can all occur in HHT 2. It also
      adds to the evidence suggesting that pulmonary AVMs are more common in HHT 1 than
      in HHT 2. We identify a higher prevalence of hepatic AVMs than previously
      reported in either HHT 1 or 2. This may be specific to the mutation in this
      kindred, but probably reflects the lack of routine screening for this
      manifestation. Even in this family in which all affected individuals have the
      same mutation, the clinical manifestations of HHT and their severity varied
      tremendously. Intrafamilial variation in expression of HHT is clearly
      significant, emphasizing the difficulty in establishing the diagnosis in
      individuals and in sub-typing families when DNA testing is not available.

PMID- 10946362
TI  - Lenz-Majewski hyperostotic dwarfism: reexamination of the original patient.
AB  - In 1974, Lenz and Majewski gave a short description of a 2-year-old girl with
      generalized hyperostosis, proximal symphalangism, syndactyly, brachydactyly,
      cutis laxa, mental retardation, marked hypertelorism, and enamel hypoplasia. This
      disorder was later named Lenz-Majewski hyperostotic dwarfism. We describe the
      reexamination of the original patient at the age of 30 years.

PMID- 10946361
TI  - Polymicrogyria associated with scalp and limb defects: variant of Adams-Oliver
      syndrome.
AB  - We describe cortical malformations in two siblings who also had features of Adams
      Oliver syndrome (AOS, MIM 100300). The parents were first cousins and showed no
      signs of either disorder, suggesting autosomal recessive inheritance. Psychomotor
      delay was present in both sibs, and cerebral imaging was indicative of
      polymicrogyria (PMG). One sib had aplasia cutis congenita of the scalp and
      transverse limb defects, and the other had short fingers and toes and also
      developed lymphedema of the right leg. CNS abnormalities and lymphatic
      abnormalities are rare manifestations of AOS, and we suggest that these sibs have
      a rare variant of AOS with probable recessive inheritance.

PMID- 10946363
TI  - Limb deficiencies in infants with trisomy 13.
AB  - In 1994, we published a case with trisomy 13 who presented with ectrodactyly
      [Urioste et al., 1994: Am J Med Genet 53:390-392]. Recently, Kuschel and
      Gillessen-Kaesbach [2000: Am J Med Genet 90:87-88] presented an infant with
      trisomy 13 who also had oligodactyly, and they considered their case as the
      second published with oligodactyly. Here, we present three cases with any type of
      limb deficiencies who, together with the one that was published previously
      [Urioste et al., 1994], correspond to the total of 75 cases with trisomy 13
      identified in the Spanish Collaborative Study of Congenital Malformations
      (ECEMC). This gives us a minimum frequency of 5.33% (CI:1.45-13.65) for trisomy
      13 cases having limb deficiencies whereas these defects have a frequency of 5.51
      per 10,000 births in our population. Consequently, we think that limb
      deficiencies could be considered as one of the defects that constitute the
      spectrum of anomalies observed in infants with trisomy 13.

PMID- 10946364
TI  - The devil of the one letter code and the Ehlers-Danlos syndrome: corrigendum.

PMID- 10946365
TI  - Expertise and category-based induction.
AB  - The authors examined inductive reasoning among experts in a domain. Three types
      of tree experts (landscapers, taxonomists, and parks maintenance personnel)
      completed 3 reasoning tasks. In Experiment 1, participants inferred which of 2
      novel diseases would affect "more other kinds of trees" and provided
      justifications for their choices. In Experiment 2, the authors used modified
      instructions and asked which disease would be more likely to affect "all trees."
      In Experiment 3, the conclusion category was eliminated altogether, and
      participants were asked to generate a list of other affected trees. Among these
      populations, typicality and diversity effects were weak to nonexistent. Instead,
      experts' reasoning was influenced by "local" coverage (extension of the property
      to members of the same folk family) and causal-ecological factors. The authors
      concluded that domain knowledge leads to the use of a variety of reasoning
      strategies not captured by current models of category-based induction.

PMID- 10946366
TI  - Category learning with minimal prior knowledge.
AB  - In 6 experiments, the authors examined the use of prior knowledge in category
      learning. Previous studies of the effects of knowledge on category learning have
      used categories in which knowledge was related to all of the category's features.
      However, people's knowledge of real-world categories often consists of many
      "rote" features that are not related to their prior knowledge. Five experiments
      found that even minimal prior knowledge (1 knowledge-relevant feature and 5 rote
      features per exemplar) can facilitate category learning. Posttests revealed that
      although the knowledge aided learning, subjects also acquired the rote features
      that were not related to knowledge, contradicting predictions of an attentional
      explanation of the knowledge effect. The results of Experiment 6 suggested that
      subjects attempt to link even rote features to their knowledge.

PMID- 10946367
TI  - The role of similarity in artificial grammar learning.
AB  - The authors examine the role of similarity in artificial grammar learning (AGL;
      A. S. Reber, 1989). A standard finite-state language was used to create stimuli
      that were arrangements of embedded geometric shapes (Experiment 1), connected
      lines (Experiment 2), and sequences of shapes (Experiment 3). Main effects for
      well-known predictors from the literature (grammaticality, associative global and
      anchor chunk strength, novel global and anchor chunk strength, length of items,
      and edit distance) were observed, thus replicating previous work. However, the
      authors extend previous research by using a widely known similarity-based
      exemplar model of categorization (the generalized context model; R. M. Nosofsky,
      1989) to fit grammaticality judgments, by nested regression analyses. The results
      suggest that any explanation of AGL that is based on the existing theories is
      incomplete without a similarity process as well. Also, the results provide a
      foundation for further interpreting AGL in the wider context of categorization
      research.

PMID- 10946368
TI  - The role of stimulus-based and response-based spatial information in sequence
      learning.
AB  - In 4 experiments, relational structures were independently varied in stimulus and
      response sequences in a serial reaction time task. Moreover, the use of spatial
      and symbolic stimuli and responses was varied between experiments. In Experiment
      1, spatial stimuli (asterisk locations) triggered spatial responses (keystrokes);
      in Experiment 2, spatial stimuli triggered symbolic responses (verbal digit
      naming); in Experiment 3, symbolic stimuli (digits) triggered keystrokes; and in
      Experiment 4, digits triggered verbal responses. The results showed that there is
      a remarkably stronger effect of relational structures in spatial sequences than
      in symbolic sequences, irrespective of whether stimulus or response sequences are
      concerned. This suggests that learning is particularly effective for sequences of
      spatial locations. It is argued that spatial learning is a critical determinant
      for the debate on perceptual and motor learning.

PMID- 10946369
TI  - Probabilities and polarity biases in conditional inference.
AB  - A probabilistic computational level model of conditional inference is proposed
      that can explain polarity biases in conditional inference (e.g., J. St. B. T.
      Evans, 1993). These biases are observed when J. St. B. T. Evans's (1972)
      negations paradigm is used in the conditional inference task. The model assumes
      that negations define higher probability categories than their affirmative
      counterparts (M. Oaksford & K. Stenning, 1992); for example, P(not-dog) > P(dog).
      This identification suggests that polarity biases are really a rational effect of
      high-probability categories. Three experiments revealed that, consistent with
      this probabilistic account, when high-probability categories are used instead of
      negations, a high-probability conclusion effect is observed. The relationships
      between the probabilistic model and other phenomena and other theories in
      conditional reasoning are discussed.

PMID- 10946370
TI  - Updating geographical knowledge: principles of coherence and inertia.
AB  - In 2 experiments, the authors investigated how representations of global
      geography are updated when people learn new location information about individual
      cities. Participants estimated the latitude of cities in North America
      (Experiment 1) and in the Old and New Worlds (Experiment 2). After making their
      first estimates, participants were given information about the latitudes of 2
      cities and asked to make a second set of estimates. Both the first and second
      estimates revealed evidence for psychologically distinct geographical subregions
      that were coordinated, in an ordinal sense, across the Atlantic Ocean. Further,
      the second estimates were affected by the nature of the physical adjacency
      between regions (e.g., the southern U.S. and Mexico) and by accurate location
      information about distant, but coordinated, subregions (e.g., the southern U.S.
      and Mediterranean Europe). The data provide support for a framework for making
      geographical estimates in which people strike a balance between 2 principles: the
      need to keep their knowledge base coherent, and the inertial tendency to resist
      changing the knowledge base unless it is necessary to maintain coherence.

PMID- 10946371
TI  - Recognizing objects seen from novel viewpoints: effects of view similarity and
      time.
AB  - View combination refers to a process that allows generalization to novel views of
      an object by the combination of object views represented in memory. The present
      experiments examined whether the perceived similarity between views or the
      temporal separation of views poses constraints on the view combination process.
      The results indicated that, although similar views are mapped onto the same
      object more easily than dissimilar views, dissimilar views, when experienced
      contiguously in time, produce greater generalization after view combination than
      similar views. These findings suggest that although the mapping of dissimilar
      views to the same object is difficult, exposure to temporally contiguous
      dissimilar views produces better generalization than does exposure to similar
      views, presumably because they provide more structural information about the
      object. However, view combination appears to be constrained to views experienced
      contiguously in time.

PMID- 10946372
TI  - Surface segmentation cues influence negative priming for novel and familiar
      shapes.
AB  - In a series of experiments, a negative priming paradigm was used to determine how
      the visual system represents novel shapes under conditions of inattention.
      Observers in a shape-matching task viewed overlapping shapes with or without
      surface segmentation cues. Positive priming occurred with opaque and transparent
      surface-like shapes, whereas negative priming was found with outlined and
      transparent shapes that lacked surface segmentation cues. This effect generalized
      to familiar shapes. These results support the importance of segmentation cues in
      negative priming and suggest that, under otherwise identical conditions, surface
      segmentation processes can determine whether positive or negative priming occurs
      in an implicit memory task. Thus, selective attention for overlapping shapes may
      be best understood in relation to surface segmentation processes.

PMID- 10946373
TI  - Repetition priming of words, pseudowords, and nonwords.
AB  - In 5 experiments, the authors assessed repetition priming for words, pseudowords,
      and nonwords using a task that combines an implicit perceptual fluency measure
      and a recognition memory assessment for each list item. Words and pseudowords
      generated a consistently strong repetition effect even when there was a failure
      to recognize the stimulus. In 2 of the experiments, the repetition effect for
      nonwords was reliably above chance even when there was a failure to recognize the
      stimulus. The authors propose a parallel distributed processing (PDP) model based
      on the work of J. McClelland and D. Rumelhart (1985) as a way to understand the
      mechanisms potentially responsible for the pattern of findings. Although the
      error-driven nature of learning in the model results in a poor fit to the nonword
      priming data, this is not endemic to all PDP models. Using a model based on
      Hebbian learning, the authors instantiate a property that they believe is
      characteristic of implicit memory--that learning is primarily based on the
      strengthening of connections between units that become active during the
      processing of a stimulus. This model provides a far more satisfactory account of
      the data than does the error-driven model.

PMID- 10946374
TI  - Semantic processing without conscious identification: evidence from event-related
      potentials.
AB  - Three event-related potential (ERP) experiments examined whether semantic content
      can be accessed from visually presented words that cannot be consciously
      identified. Category labels were shown to participants, followed by masked,
      briefly exposed words that were either exemplars of the category or not
      exemplars. The task was to verify the category, by guessing if necessary, and to
      identify the word, naming it if possible. Exposure durations were selected to
      allow identification in approximately half the trials. For identified words,
      there was a marked difference in the ERP response between in-category and out-of
      category words because of an N400 component. For unidentified words, there was a
      similar although smaller difference. Conscious identification was defined using a
      variety of approaches: verbal report, 6-alternative forced choice, and binary
      categorization (in the context of the regression method; A. G. Greenwald, M. R.
      Klinger, & E. S. Schuh, 1995). By any definition, ERPs for unidentified words
      showed evidence of semantic processing. In addition, there were differences in
      the neuronal populations recruited to process above-threshold versus below
      threshold words, suggesting qualitative differences.

PMID- 10946375
TI  - When lust is lost: orthographic similarity effects in the encoding and
      reconstruction of rapidly presented word lists.
AB  - A reconstructive account of memory is presented to explain the finding that
      report of a word (C2) appearing in a rapidly presented list is reduced when it is
      orthographically similar to an earlier word (C1) in the list. By this account,
      the effect arises when the list is reconstructed from memory, not at the time of
      list presentation as proposed by accounts based on failure of encoding or
      tokenization. The reconstructive account is supported by a series of experiments
      that show a retroactive effect in which report of C1 is enhanced by similarity to
      C2; a nonword C1 can either interfere with or enhance report of C2, depending on
      how accurately C1 is encoded; manipulation of reconstructive processes can
      eliminate or enhance the effect of orthographic similarity; and a bidirectional
      trade-off in the report of an orthographically similar C1-C2 pair, whereby report
      of one member compromises report of the other.

PMID- 10946376
TI  - Differential effects of cue dependency on item and source memory.
AB  - The authors investigated the cue dependency of source and item memory.
      Individuals listened to words spoken by a man or a woman and later determined
      whether a test word was previously presented by a man or by a woman, or whether
      it was a new word. Cue dependent effects were assessed by presenting test words
      with (a) the same voice (match condition) that originally presented the word, (b)
      a different but familiar voice (mismatch condition), (c) a novel test voice
      (novel condition), and (d) no test voice (control condition). Compared with the
      control condition, source recollection was facilitated in matching-context
      conditions, disrupted in mismatching-context conditions, and not affected in
      novel test conditions. By contrast, item recognition was not affected by the
      match-mismatch manipulation but was significantly worse in novel test voice
      conditions. The authors propose an associative source interference view to
      account for the voice match-mismatch effects observed in source recollection.

PMID- 10946377
TI  - Order information and retrieval distinctiveness: recall of common versus bizarre
      material.
AB  - The order-encoding hypothesis (E. L. DeLosh & M. A. McDaniel, 1996) assumes that
      serial-order information contributes to the retrieval of list items and that
      serial-order encoding is better for common items than bizarre items. In line with
      this account, Experiment 1 revealed better free recall and serial-order memory
      for common than for bizarre items in pure lists, and Experiment 2 showed that
      recall for bizarre items increased and the recall advantage of common items was
      eliminated when serial-order encoding for bizarre items was increased to the
      level of common items. However, inconsistent with a second assumption that
      bizarre-item advantages in mixed lists reflect better individual-item encoding
      for bizarre items, Experiments 3 and 4 showed that the bizarreness effect in
      mixed lists is eliminated when alternative retrieval strategies are encouraged.
      This set of findings is better explained by the differential-retrieval-process
      framework, which proposes that contextual factors (e.g., list composition)
      influence the extent to which various types of information are used at retrieval,
      with the bizarreness advantage in mixed lists dependent on a distinctiveness
      based retrieval process.

PMID- 10946378
TI  - The category access measure of relational processing.
AB  - Increases in category access (CA) and items recalled per category (IPC) are
      associated with increases in relational and item-specific processing,
      respectively. However, it has also been shown that CA increases as recall level
      increases and that CA scores following relational processing are actually below
      CA scores for randomly recalled items. These results prompted M. D. Murphy (1979)
      to suggest that, after adjusting for recall-level differences, relational
      processing decreases CA scores. Results of Experiment 1, along with a reanalysis
      of previously published data, showed that relational processing produces lower CA
      scores than purely item-specific processing (or random recall), but an increase
      in relational processing produces an increase in CA scores even when the CA and
      IPC scores are adjusted for recall-level differences. These results suggest a
      curvilinear relationship between relational processing and CA scores.

PMID- 10946379
TI  - Recognition without identification.
AB  - The ability of people to recognize words that they could not identify was
      examined. After studying a list of 15 words, participants completed a word
      fragment test consisting of 4-letter fragments of both studied and nonstudied
      words. Whether they were able to solve a particular fragment or not, participants
      then made an episodic recognition judgment. Even when participants were unable to
      solve a fragment, their recognition accuracy was significantly higher than
      chance. This effect was significant when list length was increased, when 2-letter
      fragments were used, when first letters were excluded from fragments, and when
      the letter casing and the presentation modality were changed from study to test.
      It also occurred when participants attempted to identify fragments at study and
      rated words at test. Recognition without identification is attributed to the use
      of orthographic information when determining the familiarity of a test item.

PMID- 10946380
TI  - Conceptual fluency selectively influences knowing.
AB  - Research shows that Remember and Know judgments are effective measures of
      recollective experience. This article shows that Know responses can be
      selectively affected by fluency of processing that is created using a conceptual
      manipulation. In a recognition test, studied and nonstudied words were preceded
      by semantically related or unrelated primes. Participants gave significantly more
      Know judgments to items with related primes than unrelated primes but Remember
      responses were unaffected. Know responses are discussed in terms of familiarity
      assumed to arise from fluency of processing which, in turn, may be created
      through various sources including conceptual processes.

PMID- 10946381
TI  - Qui tam claims: threat to voluntary compliance programs in health care
      organizations.
AB  - The Department of Justice (DOJ) reports that after violent crime, health care
      fraud is the department's top priority. The number of health care fraud
      investigations pending at the DOJ increased from 270 cases in 1992 to more than
      4,000 in 1997. The DOJ's primary weapon in prosecuting health care fraud is the
      federal False Claims Act (FCA) of 1863 (31 U.S.C. secs. 3729-3733). Almost unique
      among federal antifraud provisions, the FCA may also be used by "private
      prosecutors" to file lawsuits on behalf of the federal government charging
      organizations with submitting false claims to the government. The FCA rewards
      such whistle-blowers with a share of any resulting recoveries as a bounty and
      protects them from discharge for filing false claims lawsuits against their
      employers. It also requires defendants to pay the costs and attorneys fees of
      successful claimants. Although the private "bounty hunter" features of the FCA
      data back to the Civil War, these so-called qui tam claims were nearly dormant
      until 1986, when Congress amended the FCA to revive their use. Following the 1986
      amendments, and paralleling the rapid increase in federal reimbursements for
      health care costs, private qui tam claims have far expanded beyond their
      traditional purview of defense contracts into the field of health care. By 1997,
      health care providers were the targets of 54 percent of the 530 private qui tam
      lawsuits field that year.

PMID- 10946382
TI  - Does chronic illness affect the adequacy of health insurance coverage?
AB  - Although chronically ill individuals need protection against high medical
      expenses, they often have difficulty obtaining adequate insurance coverage due to
      medical underwriting practices used to classify and price risks and to define and
      limit coverage for individuals and groups. Using data from healthy and
      chronically ill individuals in Indiana, we found that chronic illness decreased
      the probability of having adequate coverage by about 10 percentage points among
      all individuals and by about 25 percentage points among single individuals.
      Preexisting condition exclusions were a major source of inadequate insurance,
      though not the only cause. Our results emphasize the impact of enforcing the
      Health Insurance Portability and Accountability Act (HIPAA) of 1997, which limits
      preexisting condition exclusions.

PMID- 10946383
TI  - Physicians' conflicts of interest in Japan and the United States: lessons for the
      United States.
AB  - Japanese health policy shows that even with physician ownership and the absence
      of for-profit, investor-owned health care, physicians' conflicts of interest
      thrive. Physician dispensing of drugs and ownership of hospitals and clinics were
      justified in Japan as ways to avoid commercialization of medicine. Instead, they
      create physicians' conflicts and fuel patient overuse of services. Japan's
      Ministry of Health and Welfare (MHW) has responded by introducing per-diem
      payment, thereby creating incentives to decrease services in ways similar to
      those of American managed care organizations, but with none of their benefits,
      such as coordination of care, oversight of physicians practices, and quality
      assurance. Although the United States and Japanese health care systems are
      organized and financed differently there is convergence in the source of their
      physicians' conflicts and the way they are addressed. The United States is
      starting to integrate institutional and physician payment and align their
      incentives, in a traditional Japanese way. In so doing, the United States creates
      new physicians' conflicts and reduces the role of countervailing incentives and
      power, an advantage of previous policy. Japan, in turn, has combined incentives
      to increase and decrease services, thus moving closer to the U.S. policy.

PMID- 10946384
TI  - On the structure of the euthanasia debate: observations provoked by a near
      perfect for-and-against book.

PMID- 10946386
TI  - "A tempest in a cocktail glass": mothers, alcohol, and television, 1977-1996.
AB  - This article examines the portrayal of pregnancy and alcohol in thirty-six
      national network evening news broadcasts (ABC, CBS, NBC). Early coverage focused
      on white, middle-class women, as scientific authorities and government officials
      warned against drinking during pregnancy. After 1987, however, women who drank
      during pregnancy were depicted as members of minority groups and as a danger to
      society. The thematic transition began before warning labels appeared on
      alcoholic beverages and gained strength from official government efforts to
      prevent fetal alcohol syndrome. The greatest impetus for the revised discourse,
      however, was the eruption of a "moral panic" over crack cocaine use. By linking
      fetal harm to substance abuse, the panic suggested it was in the public's
      interest to control the behavior of pregnant women.

PMID- 10946385
TI  - Mass screening in low-income populations: the challenges of securing diagnostic
      and treatment services in a national cancer screening program.
AB  - Funding for many mass screening programs for low-income and uninsured populations
      provides resources for screening tests, yet only rarely does it provide coverage
      for necessary follow-up diagnostic and treatment services. The National Breast
      and Cervical Cancer Early Detection Program (NBCCEDP), a federally funded
      initiative that provides cancer screening to low-income uninsured and
      underinsured women, covers some diagnostic follow-up tests and no treatment
      services. We conducted in-depth case studies of seven state programs
      participating in the NBCCEDP to investigate the strategies and approaches being
      used to secure diagnostic and treatment services. The results suggest that the
      program relies on a patchwork of resources--at state and local levels--to provide
      diagnostic and treatment services. This includes a number of components of local
      safety nets, all of which are unstable and have uncertain futures. Public health
      disease-screening initiatives need to reconsider the feasibility of continued
      reliance on case-by-case appeals to the local safety net for diagnostic follow-up
      and treatment services.

PMID- 10946387
TI  - The jury is still in: Florida's Birth-Related Neurological Injury Compensation
      Plan after a decade.
AB  - Florida's Birth-Related Neurological Injury Compensation Plan (NICA) is the most
      significant experiment with compensation for medical injury yet undertaken in the
      United States. As NICA enters its second decade of operation, maintaining the
      scheme's jurisdictional integrity has emerged as a key challenge for policy
      makers in Florida. We explore the relationship that has emerged between NICA and
      the tort system as competing avenues for families to obtain compensation for
      severe birth-related neurological injury. By linking NICA claims data with data
      on malpractice claims filed in Florida, we found a lively persistence of "bad
      baby" litigation despite NICA's implementation. Many families pursued claims in
      both fora. An explanation for these results can be traced to key features of the
      plan's design--primarily, the way in which "exclusive" jurisdiction over injuries
      is determined and the restrictive nature of the compensation criteria used. Our
      findings may help efforts to consolidate NICA's role in injury compensation and
      inform future design of alternative compensation systems.

PMID- 10946388
TI  - The determinants of time off work after childbirth.
AB  - Relatively little is known about the role that leave policies--family, parental,
      or maternity-leave policies--play in facilitating time off work after childbirth.
      Yet time off is a critical element of leave policies, as it facilitates the
      mother's recovery from childbirth and promotes maternal-infant attachment. Using
      data from Minnesota, the state with the highest rate of female labor force
      participation, we examine the extent to which policies, relative to personal,
      job, and workplace characteristics, determine the duration of women's childbirth
      related leaves from work. A random sample of women identified from vital
      statistics records is used to estimate the relationship between leave policies
      and time off work after childbirth. Of our sample 85 percent had access to some
      paid leave benefits, although only 46 percent had paid maternity leave benefits.
      The difference in duration of leave between women with and without paid leave
      policies was approximately four weeks, a substantial difference for most women
      and their infants. Paid leave policies and spousal earnings as primary
      determinants of maternal time off work, suggest problems in the use of unpaid
      leave for economically vulnerable women.

PMID- 10946389
TI  - Bias reduction in skewed binary classification with Bayesian neural networks.
AB  - The Bayesian evidence framework has become a standard of good practice for neural
      network estimation of class conditional probabilities. In this approach the
      conditional probability is marginalised over the distribution of network weights,
      which is usually approximated by an analytical expression that moderates the
      network output towards the midrange. In this paper, it is shown that the network
      calibration is considerably improved by marginalising to the prior distribution.
      Moreover, marginalisation to the midrange can seriously bias the estimates of the
      conditional probabilities calculated from the evidence framework. This is
      especially the case in the modelling of censored data.

PMID- 10946390
TI  - Independent component analysis: algorithms and applications.
AB  - A fundamental problem in neural network research, as well as in many other
      disciplines, is finding a suitable representation of multivariate data, i.e.
      random vectors. For reasons of computational and conceptual simplicity, the
      representation is often sought as a linear transformation of the original data.
      In other words, each component of the representation is a linear combination of
      the original variables. Well-known linear transformation methods include
      principal component analysis, factor analysis, and projection pursuit.
      Independent component analysis (ICA) is a recently developed method in which the
      goal is to find a linear representation of non-Gaussian data so that the
      components are statistically independent, or as independent as possible. Such a
      representation seems to capture the essential structure of the data in many
      applications, including feature extraction and signal separation. In this paper,
      we present the basic theory and applications of ICA, and our recent work on the
      subject.

PMID- 10946391
TI  - Evolutionary robots with on-line self-organization and behavioral fitness.
AB  - We address two issues in Evolutionary Robotics, namely the genetic encoding and
      the performance criterion, also known as the fitness function. For the first
      aspect, we suggest to encode mechanisms for parameter self-organization, instead
      of the parameters themselves as in conventional approaches. We argue that the
      suggested encoding generates systems that can solve more complex tasks and are
      more robust to unpredictable sources of change. We support our arguments with a
      set of experiments on evolutionary neural controllers for physical robots and
      compare them to conventional encoding. In addition, we show that when also the
      genetic encoding is left free to evolve, artificial evolution will select to
      exploit mechanisms of self-organization. For the second aspect, we shall discuss
      the role of the performance criterion, als known as fitness function, and suggest
      Fitness Space as a framework to conceive fitness functions in Evolutionary
      Robotics. Fitness Space can be used as a guide to design fitness functions as
      well as to compare different experiments in Evolutionary Robotics.

PMID- 10946392
TI  - A generalized Hebbian rule for activity-dependent synaptic modifications.
AB  - In this paper our previous model of activity-dependent synaptic modification is
      extended and applied to a model neuron with active dendrites and is used in
      computer simulations to examine in detail the dependence of synaptic
      modifications on the interval between the onset of excitatory postsynaptic
      potentials (EPSPs) and postsynaptic action potentials (APs). The EPSP amplitude
      is increased when the action potentials occur within 20 ms after EPSPs and is
      reduced when the action potentials occur within 20 ms before EPSPs. Furthermore,
      the absolute value of changes in the EPSP amplitude tends to increase as the
      interval between APs and EPSPs decreases. A learning rule for synaptic
      modifications described in this paper may, hence, further generalize the Hebbian
      rule which requires conjunctive presynaptic and postsynaptic activity for
      synaptic modification to occur. Functional roles for such a generalized Hebbian
      rule are also considered.

PMID- 10946394
TI  - Construction of confidence intervals for neural networks based on least squares
      estimation.
AB  - We present the theoretical results about the construction of confidence intervals
      for a nonlinear regression based on least squares estimation and using the linear
      Taylor expansion of the nonlinear model output. We stress the assumptions on
      which these results are based, in order to derive an appropriate methodology for
      neural black-box modeling; the latter is then analyzed and illustrated on
      simulated and real processes. We show that the linear Taylor expansion of a
      nonlinear model output also gives a tool to detect the possible ill-conditioning
      of neural network candidates, and to estimate their performance. Finally, we show
      that the least squares and linear Taylor expansion based approach compares
      favorably with other analytic approaches, and that it is an efficient and
      economic alternative to the nonanalytic and computationally intensive bootstrap
      methods.

PMID- 10946393
TI  - Mutual information of sparsely coded associative memory with self-control and
      ternary neurons.
AB  - The influence of a macroscopic time-dependent threshold on the retrieval dynamics
      of attractor associative memory models with ternary neurons ?-1, 0, +1? is
      examined. If the threshold is chosen appropriately as a function of the cross
      talk noise and of the activity of the memorized patterns in the model, adapting
      itself in the course of the time evolution, it guarantees an autonomous
      functioning of the model. Especially in the limit of sparse coding, it is found
      that this self-control mechanism considerably improves the quality of the fixed
      point retrieval dynamics, in particular the storage capacity, the basins of
      attraction and the information content. The mutual information is shown to be the
      relevant parameter to study the retrieval quality of such sparsely coded models.
      Numerical results confirm these observations.

PMID- 10946395
TI  - A new algorithm for learning in piecewise-linear neural networks.
AB  - Piecewise-linear (PWL) neural networks are widely known for their amenability to
      digital implementation. This paper presents a new algorithm for learning in PWL
      networks consisting of a single hidden layer. The approach adopted is based upon
      constructing a continuous PWL error function and developing an efficient
      algorithm to minimize it. The algorithm consists of two basic stages in searching
      the weight space. The first stage of the optimization algorithm is used to locate
      a point in the weight space representing the intersection of N linearly
      independent hyperplanes, with N being the number of weights in the network. The
      second stage is then called to use this point as a starting point in order to
      continue searching by moving along the single-dimension boundaries between the
      different linear regions of the error function, hopping from one point
      (representing the intersection of N hyperplanes) to another. The proposed
      algorithm exhibits significantly accelerated convergence, as compared to standard
      algorithms such as back-propagation and improved versions of it, such as the
      conjugate gradient algorithm. In addition, it has the distinct advantage that
      there are no parameters to adjust, and therefore there is no time-consuming
      parameters tuning step. The new algorithm is expected to find applications in
      function approximation, time series prediction and binary classification
      problems.

PMID- 10946396
TI  - Evolution and generalization of a single neurone. III. Primitive, regularized,
      standard, robust and minimax regressions.
AB  - We show that during training the single layer perceptron, one can obtain six
      conventional statistical regressions: a primitive, regularized, standard, the
      standard with the pseudo-inversion of the covariance matrix, robust, and minimax
      (support vector). The complexity of the regression equation increases with an
      increase in the number of iterations. The generalization accuracy depends on the
      type of the regression obtained during the training, on the data, learning-set
      size, and, in certain cases, on the distribution of components of the weight
      vector. For small intrinsic dimensionality of the data and certain distributions
      of components of the weight vector the single layer perceptron can be trained
      even with very short learning sequences. The type of the regression obtained in
      SLP training should be controlled by the sort of cost function as well as by
      training parameters (the number of iterations, learning step, etc.). Whitening
      data transformation prior to training the perceptron is a tool to incorporate a
      prior information into the prediction rule design, and helps both to diminish the
      generalization error and the training time.

PMID- 10946397
TI  - Determining the number of centroids for CMLP network.
AB  - In our recent studies we have proposed and investigated a centroid-based
      multilayer perceptron (CMLP) network architecture for modelling purposes. In the
      CMLP network the first hidden layer is a centroid layer. We have found that the
      proposed hybrid can provide significant advantages over standard multilayer
      perceptron networks in terms of fast and efficient learning, and compact network
      structure in complex classification problems. Previously the number of units for
      the centroid layer had been determined empiricially. Here we extend our work by
      introducing a method for determining the minimal number of centroid units for a
      given problem. The proposed scheme also enables efficient initialization of the
      centroids units. In addition, we also propose an initialization scheme for the
      MLP part of the CMLP network. Our benchmark simulations show that the proposed
      methods significantly improve the CMLP scheme.

PMID- 10946398
TI  - Defining a neural network controller structure for a rubbertuator robot.
AB  - Rubbertuator (Rubber-Actuator) robot arm is a pneumatic robot, unique with its
      lightweight, high power, compliant and spark free nature. Compressibility of air
      in the actuator tubes and the elastic nature of the rubber, however, are the two
      major sources of increased non-linearity and complexity in motion control. Soft
      computing, exploiting the tolerance of uncertainty and vagueness in cognitive
      reasoning has been offering easy to handle, robust, and low-priced solutions to
      several non-linear industrial applications. Nonetheless, the black-box approach
      in these systems results in application specific architectures with some
      important design parameters left for fine tuning (i.e. number of nodes in a
      neural network). In this study we propose a more systematic method in defining
      the structure of a soft computing technique, namely the backpropagation neural
      network, when used as a controller for rubbertuator robot systems. The structure
      of the neural network is based on the physical model of the robot, while the
      neural network itself is trained to learn the trajectory independent parameters
      of the model that are essential for defining the robot dynamics. The proposed
      system performance was compared with a well-tuned PID controller and shown to be
      more accurate in trajectory control for rubbertuator robots.

PMID- 10946399
TI  - An efficient learning algorithm for improving generalization performance of
      radial basis function neural networks.
AB  - This paper presents an efficient recursive learning algorithm for improving
      generalization performance of radial basis function (RBF) neural networks. The
      approach combines the rival penalized competitive learning (PRCL) [Xu, L.,
      Kizyzak, A. & Oja, E. (1993). Rival penalized competitive learning for clustering
      analysis, RBF net and curve detection, IEEE Transactions on Neural Networks, 4,
      636-649] and the regularized least squares (RLS) to provide an efficient and
      powerful procedure for constructing a minimal RBF network that generalizes very
      well. The RPCL selects the number of hidden units of network and adjusts centers,
      while the RLS constructs the parsimonious network and estimates the connection
      weights. In the RLS we derived a simple recursive algorithm, which needs no
      matrix calculation, and so largely reduces the computational cost. This combined
      algorithm significantly enhances the generalization performance and the real-time
      capability of the RBF networks. Simulation results of three different problems
      demonstrate much better generalization performance of the present algorithm over
      other existing similar algorithms.

PMID- 10946401
TI  - Application of PFGE performed with XbaI to an epidemiological and phylogenetic
      study of Salmonella serotype typhimurium. Relations between genetic types and
      phage types.
AB  - PFGE performed with XbaI was evaluated and applied as a typing method in a series
      of 68 Salmonella serotype Typhimurium strains collected in a Spanish region
      throughout 1984-1994, and four reference strains. Using bands > 100 kb as a
      separation criterion, 26 pulsed-field profiles (PFPs) were defined, with a
      discrimination index of 0.87. The XbaI-profiles were grouped into three clusters
      and two additional branches in a dendrogram of similarity (significance level =
      0.7). Strains belonging to PFP-X1 and PFP-X2 predominated (26.4% and 23.6%,
      respectively) and fell into the major cluster. The series had been previously
      analysed by phage typing and a three-way ribotyping procedure, and a certain
      degree of relation among the three methods was revealed, PFGE being the most
      discriminatory. Combining data from the three methods a further differentiation
      into 46 clonal lines was obtained, and four lines, at least, could be considered
      as endemic in the region under study. This procedure proved to be a powerful
      epidemiological tool for characterization of Typhimurium and in the investigation
      of outbreaks.

PMID- 10946400
TI  - Detection of same sized 4.3 Kb extrachromosomal DNA elements in weakly beta
      haemolytic human intestinal spirochaetes and Serpulina pilosicoli of swine
      origin.
AB  - Agarose gel electrophoresis of total DNA from Italian strains of weakly beta
      haemolytic human intestinal spirochaetes (w beta HIS) and porcine Serpulina
      pilosicoli reference strain P43/6/78 showed an extrachromosomal band having the
      same size and migrating at 4.3 Kb. The same results were observed after agarose
      gel electrophoresis of DNA obtained from the supernatant fluids of the
      spirochaetal cultures analysed. Swine Serpulina hyodysenteriae reference strain
      P18A was comparatively analysed and a 6.5 Kb extrachromosomal DNA element was
      found, as expected. Furthermore, S. hyodysenteriae reference strain P18A differed
      from all the other spirochaetes tested and had a higher number of flagella (8-12)
      at each cell end and was strongly beta-haemolytic. To the best of our knowledge,
      this is the first report on the detection of a band of extrachromosomal DNA
      having the same size in w beta HIS and S. pilosicoli from swine origin.

PMID- 10946402
TI  - Association between lesional or non lesional S. aureus strains from patients with
      impetigo and exfoliative toxin production. No association with SmaI PFGE
      patterns.
AB  - Contrasting data are reported in the literature on the percent positivity rates
      (13.5%-100%) of exfoliative toxin (ET) production by S. aureus strains isolated
      from impetigo patients in Japan and in France. In the present study, by means of
      a recently available latex-test, toxin-A (ETA) or toxin-B (ETB) production was
      found in 67.6% of the 34 S. aureus strains isolated from 19 lesional (63.2%) and
      15 non-lesional (nose or pharynx, 73.3%) areas of patients with impetigo (with no
      significant difference between the lesional and non-lesional isolates). ETA + ETB
      were produced by 44.1% of the strains, while 32.4% were non-producers. In
      contrast, the percent positivity rate observed in 40 [20 lesional and 20 non
      lesional (nose or pharynx)] strains isolated in patients with atopic dermatitis
      was 15.0% (p < 0.001 both for the lesional and non-lesional strains versus
      impetigo, with no significant difference between lesional and non lesional
      strains). Finally, 26 strains from other types of specimens (abscesses,
      hemocultures, urine, central venous catheters, bronchoalveolar lavages) showed an
      11.5% production rate of ETA or ETB (p < 0.001 versus impetigo strains, no
      significance versus atopic dermatitis). These data point to a significant
      association between exfoliative toxin production and S. aureus strains isolated
      in impetigo, both in lesional areas and in nasal/pharyngeal reservoirs. An
      attempt to correlate SmaI pulsed-field gel electrophoresis (PFGE) restriction
      patterns and exfoliative toxin production showed no significant association in
      either group.

PMID- 10946403
TI  - S. aureus PFGE patterns of lesional or non lesional strains from patients with
      impetigo: association of individual bands with lesional or non lesional areas.
AB  - PFGE has been extensively used to obtain a reliable intra-species
      differentiation, although this technique has not been completely standardized. In
      this study, PFGE was applied to analyze in detail the patterns of 19 lesional S.
      aureus strains isolated from patients with impetigo, compared with 15 non
      lesional strains isolated from nasal or pharyngeal swabs of the same patients.
      The strain DNA was extracted and processed as previously reported, using the
      strictest protocol to limit the variations between different analytical sets. To
      obtain maximum sensitivity and comparability, the electrophoresis patterns were
      analyzed by an automated and computerized reader (GelDoc1000). The DNA fragments
      (range 12-15 bands) obtained for each individual strain were then divided into 39
      zones including from 1 to 4 bands for a total of at least 91 possible different
      gel positions. The positivity for each zone (and/or the positivity for the
      individual bands contained) was associated with the lesional/non-lesional origin
      and with the face localization of the strains.

PMID- 10946404
TI  - Synergic activities of streptococcal pyrogenic exotoxin A and lipoteichoic acid
      in cytokine induction.
AB  - The present study was carried out to gain insight into the mechanisms involved in
      the pathogenesis of streptococcal toxic shock syndrome (TSS) and other acute
      invasive diseases caused by Streptococcus pyogenes (GAS). Specifically, since
      both whole bacteria and their soluble products are often present in the blood in
      these conditions, we sought to detect possible synergic activities of somatic and
      extracellular products in inducing mediators release. For this purpose, whole
      blood cultures from healthy donors were incubated with different concentrations
      of streptococcal pyrogenic exotoxin A (SpeA), which is considered a major
      molecular effector of TSS, heat-killed GAS and cell-wall components such as
      lipoteichoic acid (LTA) and soluble peptidoglican (sPGN). Significant levels of
      TNF-alpha, IL-1 alpha and IFN-gamma were found in supernatants from cultures
      incubated with each of the four inducers alone. Whole GAS and both cell-wall
      components were more effective (p < 0.05) than SpeA in inducing cytokine release.
      Whole GAS, at weight basis, was a more potent inducer than LTA and sPGN and LTA,
      at weight basis, was a more potent inducer than sPGN. In order to verify possible
      additive or synergic effects of exotoxic and parietal compounds in inducing
      cytokine release, whole blood cells were incubated with mixtures of SpeA and LTA
      at different molecular ratio. TNF-alpha, IL-1 alpha and IFN-gamma levels in
      supernatants were significantly (p < 0.05) higher in supernatants of cultures
      stimulated simultaneously with the two components than those of cultures
      stimulated with a single agent. Moreover, these levels were significantly higher
      than the sum of cytokine levels induced by single components. This study shows
      that parietal compounds can act in synergy with exotoxins in inducing the release
      of cytokines, which appear to be the major mediators of TSS.

PMID- 10946405
TI  - Comparison of Vero cell assay, polymerase chain reaction and an enzyme
      immunoassay for identification of verocytotoxin-producing Escherichia coli
      O157:H7.
AB  - This study evaluated three different analytical methods for identification of
      Verocytotoxin-producing E. coli O157:H7 (VTEC) strains. A total of 34 E. coli
      O157:H7 strains isolated from bovine faeces and bovine carcasses were
      comparatively tested with Vero cell assay (VCA), PCR and the sandwich ELISA
      "RIDASCREEN Verotoxin" test. The VCA, performed without a neutralization assay,
      gave a false positive result because a VCA-positive E. coli O157:H7 strain did
      not possess the VT-coding genes when tested with PCR. The lack of specificity of
      the VCA could be avoided by testing for neutralization of cytotoxicity. The
      commercial ELISA system was as sensitive and specific as PCR, with the advantages
      of being a more rapid and easier procedure which could be employed in all first
      level diagnostic laboratories.

PMID- 10946406
TI  - An immunoblotting technique for the serodiagnosis of brucellosis by Brucella
      ovis.
AB  - An immunoblotting (IB) technique was developed for the serodiagnosis of
      brucellosis caused by Brucella ovis. Immunoblotting was performed, using a B.
      ovis HS (hot saline extract) antigen, on 44 blood serum samples which came from
      rams belonging to known brucella-free flocks, 114 samples originating from ten
      experimentally B. ovis infected rams and 100 from rams of naturally B. ovis
      infected flocks. No bands were noted on any of the 44 serum samples which
      originated from known negative flocks. Sera from naturally and experimentally
      infected rams identified antibodies to antigenic components with molecular masses
      of 67, 63, 58, 55, 38, 35, 32, 30, 28, 25, 23, 21, 20-18 (proteins) and 15-12
      (RLPS) kDa.

PMID- 10946407
TI  - Effect of dietary carbohydrates on the in vitro epithelial adhesion of Candida
      albicans, Candida tropicalis, and Candida krusei.
AB  - Adhesion to epithelial surfaces is considered as a critical step in the
      pathogenesis of oral candidosis. Therefore, the effects of the most commonly
      consumed dietary carbohydrates on the adhesion of Candida albicans, Candida
      tropicalis, and Candida krusei to monolayered HeLa cells were investigated.
      Adherence of C. albicans and C. tropicalis appeared significantly promoted by
      incubation in defined medium containing a high concentration (500 mM) of
      fructose, glucose, maltose, and sucrose (p < 0.001). C. albicans organisms grown
      in sucrose elicited maximal increase in adhesion, whereas adhesion of C.
      tropicalis and C. krusei was enhanced to the greatest extent when cultured in
      glucose. Maltose and fructose also promoted adherence of C. albicans and C.
      tropicalis (p < 0.001), but to a lesser extent than sucrose and glucose. On the
      other hand, sorbitol-grown yeasts demonstrated a marginal increase in adhesion (p
      > 0.01). Xylitol only significantly reduced adherence of C. albicans (p < 0.001).
      These results suggest that the frequent consumption of carbohydrates, such as
      sucrose, glucose, maltose, or fructose, might represent a risk factor for oral
      candidosis. The limitation of their consumption by substituting xylitol or
      sorbitol could be of value in the control of oral Candida colonization and
      infection.

PMID- 10946408
TI  - Antifungal activity of rhodium, iridium, and ruthenium tripodal phosphine
      complexes.
AB  - Twenty-eight rhodium, iridium or ruthenium complexes were evaluated for their in
      vitro antifungal activities against Candida albicans and Candida tropicalis.
      Fourteen compounds showed an antifungal activity against C. albicans and C.
      tropicalis with a range of the minimum inhibitor concentrations (MICs) between 16
      and 250 micrograms/mL.

PMID- 10946409
TI  - Frequent detection of HIV-1 RNA but low rates of HIV-1 isolation in
      cervicovaginal secretions from infected women.
AB  - Information regarding the presence of HIV-1 in the female genital tract is
      necessary to gain insight into the mechanism of HIV-1 heterosexual transmission.
      Herein, we present the results of a study on virus isolation and HIV-1 RNA
      detection from cervicovaginal lavage (CVL) samples from 25 HIV-1 seropositive
      women. Despite detectable levels of HIV-1 RNA in 88% of CVL samples, HIV-1 was
      isolated in only four (19%) samples. Although HIV-1 shedding in cervicovaginal
      secretions is a common event at all disease stages, the recovery of infectious
      virus in cell cultures appears to be rare; this renders viral isolation in
      studies aimed to evaluate the infectivity of cervicovaginal secretions relatively
      useless.

PMID- 10946410
TI  - Limited secretory-IgA response in cervicovaginal secretions from HIV-1 infected,
      but not high risk seronegative women: lack of correlation to genital viral
      shedding.
AB  - The presence and antigen specificity of IgG and secretory-IgA (s-IgA) to HIV-1
      were evaluated in cervicovaginal lavages (CVL) from 26 infected and 10 high-risk
      seronegative women. All the seropositive women had detectable IgG recognizing
      several viral antigens, while a smaller percentage of women demonstrated s-IgA to
      the virus. In addition, s-IgA were of limited specificity and provided weak
      reactivities on Immunoblot bands; an almost constant absence of s-IgA to gp120
      was also observed. Neither the presence nor the specificity of either IgG or s
      IgA to the virus in CVL prevented the shedding of HIV-1 in this body fluid; in
      fact, viral RNA was detected in all the women studied and the amounts of viral
      shedding was unrelated to the genital antibody response. On the other hand, none
      of the high-risk seronegative women had detectable antibodies to HIV-1 in CVL of
      either the IgG or s-IgA isotype. Our results a) confirm an impairment of mucosal
      antibody response during HIV-1 infection and suggest that mucosal immunity is not
      able to prevent viral shedding in the female genital tract and thus cannot
      modulate the infectivity of genital secretions; aa) do not provide evidence for a
      mucosal "memory/protective" antibody response in the genital tract of high-risk
      seronegative women.

PMID- 10946411
TI  - Antigenic analysis of canine parvovirus strains isolated in Italy.
AB  - Eighty-two canine parvovirus type 2 strains isolated in Italy from pups with
      severe enteritis were characterizated using four monoclonal antibodies. Sixty
      eight isolates resulted CPV-2a, whereas the other fourteen were a CPV-2b variant.
      The diffusion of CPV-2 variants in the Italian dog population is quite similar to
      that reported in the United Kingdom and Australia (CPV-2a more prevalent) and
      different from the epidemiological conditions of the USA and other countries
      where CPV-2b is more widespread.

PMID- 10946412
TI  - Occurrence and seasonal variation of airborne gram negative bacteria in a sewage
      treatment plant.
AB  - A study was carried out to determine the microbial density and the seasonal
      variation of airborne Gram negative bacteria in a sewage treatment plant.
      Sampling was made at 16 sites and the settle plate technique was used. Of the 201
      samples examined, 43.2% revealed fecal coliforms (mean value = 14 cfu/p/h), 53%
      Pseudomonas spp. (mean value = 11 cfu/p/h), 46.5% Shigella spp. (mean value = 13
      cfu/p/h), 3% Legionella spp. (mean value = 2 cfu/p/h) and 2% Salmonella (mean
      value = < 1 cfu/p/h). 72% of the samples contained "other" Gram negative bacteria
      such as Aeromonas hydrophila, Serratia marcescens, Enterobacter cloacae and
      others. With the exception of Legionella spp. and Salmonella, all other bacteria
      were more frequent and numerous in the October-March period, when temperatures
      were lower and humidity higher. Although the oxidation tanks were covered overall
      contamination was nevertheless high, thus presenting a potential health risk for
      plant workers.

PMID- 10946413
TI  - Haemolytic uraemic syndrome.
AB  - Diarrhoea-associated haemolytic uraemic syndrome develops in about 5 to 10% of
      children with haemorrhagic colitis due to Escherichia coli (E. coli) O157:H7 and
      is a common cause of acute renal failure in childhood. Endothelial cell damage,
      white blood cell activation and platelet-endothelial cell interactions are
      important in the pathogenesis. Meticulous supportive care, with attention to
      nutrition and fluid, and electrolyte balance, is important. Dialysis is necessary
      in many children. Public health follow-up is important to minimise the spread of
      E. coli O157:H7, which is transmitted by person-to-person, as well as through
      contaminated food products. 20-year follow-up studies report that 75% of children
      recover without any clinically significant long term sequelae. Chronic renal
      failure is reported in about 5% of children.

PMID- 10946414
TI  - Management of schizophrenia in children and adolescents. The role of clozapine.
AB  - Clozapine is a dibenzodiazepine derivative with established antipsychotic
      efficacy in adult patients with schizophrenic psychoses. There are more than 15
      studies that have also demonstrated the antipsychotic efficacy of clozapine in
      childhood and adolescent schizophrenia. The main advantages of clozapine
      treatment in this age group in comparison with typical antipsychotics are: (i)
      high antipsychotic efficacy during an acute schizophrenic episode; (ii) better
      improvement in chronic cases with a high load of negative symptoms; and (iii)
      markedly fewer extrapyramidal adverse effects and, therefore, fairly good
      tolerability. However, because of its possible adverse effects on the haemopoetic
      system (granulocytopenia, agranulocytosis), clozapine should not be used as first
      line antipsychotic medication. Other adverse effects are related to the
      cardiovascular system (hypotonia, tachycardia or arrhythmia), the central nervous
      system (epileptic seizures, fever) and liver function (transient increases in
      levels of hepatic transaminases). Two other frequent adverse effects are
      hypersalivation and body-weight gain, which may present a particular problem in
      adolescents and young adults. Careful monitoring of haematological parameters and
      other adverse effects are preconditions for a successful treatment programme.

PMID- 10946416
TI  - Safety of routine childhood vaccinations. An epidemiological review.
AB  - Immunisations have been one of the most cost-effective public health
      interventions in human history. Despite remarkable progress, several challenges
      face immunisation programs worldwide. Paradoxically, despite vaccines' clear
      effectiveness in reducing risks of diseases that were previously widely prevalent
      and caused substantial morbidity and mortality, current vaccination policies have
      become increasingly controversial due to concerns about vaccine safety. Vaccines,
      like other pharmaceutical products, are not entirely risk-free. While most known
      adverse effects are minor and self-limited, some vaccines have been associated
      with very rare but serious adverse effects. Because such rare effects are often
      not evident until vaccines come into widespread use, ongoing surveillance
      programs to monitor vaccine safety are needed. Such monitoring will be essential
      if the public is to accept the increasing number of new vaccines made possible by
      biotechnology. The interpretation of data from vaccine safety research is complex
      and is associated with some uncertainty. Effectively communicating this
      uncertainty and continuing to improve understanding of rare risks and risk
      factors are essential for "mature" immunisation programs to maintain public
      confidence in immunisations.

PMID- 10946415
TI  - Role of drug therapy in the treatment of gastro-oesophageal reflux disorder in
      children.
AB  - Gastro-oesophageal reflux (GOR) is the effortless passage of gastric contents
      into the distal oesophagus. It can be classified as functional (or symptomatic),
      in which the infant remains free from disease, or a pathological (GOR disease,
      GORD), in which gastrointestinal, respiratory or neurobehavioural signs occur
      with intraoesophageal acidification and the development of oesophagitis.
      Functional or symptomatic GOR is successfully treated by conservative measures
      and does not require investigative diagnostic tools; however, both drug
      administration and an investigative approach are mandatory in patients with GORD.
      There is currently a great range of proven therapeutic options for GORD that are
      directed at counteracting the pathogenetic components of the disorder. In this
      report we discuss the role of different drug classes for treating GORD in
      children. The choice of therapy for GORD depends upon the severity of signs and
      the degree of oesophagitis. The presence of oesophagitis, as documented by
      endoscopy, suggests the use of antisecretory drugs; H2 receptor antagonists are
      the first-line agents. Nevertheless, individuals with refractory disease or those
      patients requiring potent inhibition of acid secretion (for example, GORD with
      respiratory involvement) can be given proton pump inhibitors. Other groups of
      patients who need potent inhibition of acid secretion are children with
      neurological dysfunction and those with Barrett's oesophagus. It is still unclear
      whether patients with frequent relapses are candidates for long term
      administration of antisecretory drugs or for surgical fundoplication.

PMID- 10946417
TI  - Varicella zoster infection in HIV-infected children.

PMID- 10946419
TI  - Interaction between the hepatitis C virus and the immune system.
AB  - The hepatitis C virus (HCV) causes a wide spectrum of liver diseases ranging from
      symptomatic or asymptomatic acute infection with self-limited disease to
      persistent infection with chronic active hepatitis and an increased risk of liver
      cirrhosis and hepatocellular carcinoma. The outcome of HCV infection (i.e., viral
      clearance or persistence) and the manifestation and degree of liver disease is
      the result of complicated interactions between the virus and the immune response
      of the host. Remarkably, most de novo HCV infections are clinically inapparent
      and characterized by a high incidence (70%) of chronically evolving hepatitis,
      which suggests that HCV may have evolved strategies to not induce, overcome, or
      evade efficient immune responses of the host. This may be a multifactorial
      process, influenced by viral tissue tropism, replication, sequence variation and
      by functional alteration of infected cells. The interaction between HCV and the
      specific humoral and cellular immune response of the host, the role of the liver
      as the primary site of viral replication, the target of the host's immune
      response, and potential mechanisms of viral escape are discussed.

PMID- 10946420
TI  - The lymphoid system in hepatitis C virus infection: autoimmunity, mixed
      cryoglobulinemia, and Overt B-cell malignancy.
AB  - Like other hepatotropic viruses, hepatitis C virus (HCV) shares the property of
      inducing hepatocellular damage, possibly through induction of immune mechanisms
      that lead to hepatocellular necrosis. After infection of hepatocytes, and
      possibly other cells, humoral and cellular responses occur aimed at prevention of
      virus dissemination and elimination of infected cells. The early activated
      mechanisms include production of nonspecific and specific antibodies that
      represent the first-line of defense against invading foreign pathogens. As a
      consequence, circulating immune complexes are promptly formed, and antigen uptake
      and processing by specialized cells are enhanced. A major fraction of circulating
      immunoglobulins (Igs) are part of the spectrum of the so-called natural
      antibodies, which include anti-idiotypic antibodies and molecules with rheumatoid
      factor (RF) activity. They mainly belong to the IgM class, are polyclonal, and
      have no intrinsic pathogenetic potential. In 20-30% of HCV-infected patients, RFs
      share characteristics of high affinity molecules, are monoclonal in nature, and
      result in the production of cold-precipitating immune complexes and mixed
      cryoglobulinemia. It has been shown that anti-idiotypic antibodies and polyclonal
      and monoclonal RF molecules have the same cross-reactive idiotype, called WA,
      suggesting that their production is highly restricted. This strongly indicates
      that they arise from stimulation with the same antigen, likely HCV. It has also
      been speculated that B-1 (CD5+) and B-2 (CD5-) B-cell subsets, which use a
      limited number of VH germline genes, underlie the production of low-affinity
      polyclonal and high-affinity monoclonal antibodies, respectively. The persistent
      production of monoclonal RF molecules implies the existence of a further
      mechanism capable of restricting the reactivity and reflects a distinct selection
      of a cell population that can be maintained throughout life because they are
      continuously exposed to antigen pressure. Either polyclonal or monoclonal
      profiles of B-cell expansion are demonstrable in the liver of most HCV-infected
      patients. The occurrence of B-cell clonal expansion is strictly related to
      intrahepatic production of RF molecules, and this suggests that liver is a
      microenvironment, other than lymphoid tissue, in which a germinal centerlike
      reaction is induced. The frequent detection of oligoclonal B-cell expansion may,
      indeed, represent a key pathobiologic feature that sustains nonmalignant B-cell
      lymphoproliferation. The preferential expansion of one clone would in turn lead
      to a monoclonal pattern that could favor stochastic oncogenic events. It can be
      postulated that HCV is the stimulus not only for the apparent benign
      lymphoproliferative process underlying a wide spectrum of clinical features, but
      also for the progression to frank lymphoid malignancy in a subgroup of patients.
      Current data indicate a higher prevalence of overt B-cell non-Hodgkin's lymphoma
      in HCV-infected patients, especially in some geographic areas.

PMID- 10946421
TI  - Diagnostic testing for hepatitis C.
AB  - Diagnostic tests for hepatitis C virus have improved dramatically over the past
      decade. Highly accurate tests are now available for screening patients for
      possible hepatitis C infections and confirming the presence of active viral
      infection. HCV RNA levels and genotype are very useful in assessing the
      likelihood of response to antiviral therapy and in guiding the optimum duration
      of treatment. Absence of detectable HCV RNA using PCR methodology has become the
      gold standard of successful treatment of patients with chronic hepatitis C. The
      various tests for hepatitis C are expensive and have their limitations. However,
      selective use of these assays has greatly improved the care of patients with
      chronic hepatitis C.

PMID- 10946422
TI  - Hepatitis C kinetics: mathematical modeling of viral response to therapy.
AB  - Mathematical models have been used to study the dynamics of HIV. Using these same
      principles, the dynamics of hepatitis C virus (HCV) are reviewed during
      interferon (IFN) therapy. After initiating IFN treatment, there is an IFN dose
      dependent exponential decline in viral RNA levels within the first 48 hours. This
      rapid 1.0 to 2.0 log decline was best explained by an effect of IFN in inhibiting
      viral production with a varying degree of effectiveness. By applying mathematical
      principles, viral serum half-life was estimated to be 3.0 hours and viral
      production rat was calculated to be 1.0 x 10(12) virions per day. After this
      rapid first-phase decline there was a slower second phase decline in viral levels
      that was highly variable between subjects. This phase was dependent on the rate
      of elimination of HCV-infected liver cells. The rapidity of the second phase
      proved to be the best predictor of early viral clearance. The use of these models
      to understand the life cycle of viruses and their response to therapy is
      reviewed.

PMID- 10946418
TI  - Lamotrigine. A review of its use in childhood epilepsy.
AB  - Lamotrigine is an antiepileptic agent that blocks use-dependent voltage-sensitive
      sodium channels, thereby preventing excitatory neurotransmitter release. However,
      this mechanism does not explain the broad range of clinical efficacy of this
      agent. In noncomparative trials, adjunctive lamotrigine (< or = 15 mg/kg/day)
      improved seizure control in children and adolescents with various refractory
      seizure types, with about 29 to 90% of patients showing a > or = 50% reduction in
      seizure frequency after > or = 3 months' treatment. Lamotrigine was particularly
      effective in generalised seizures, especially absence seizures and those related
      to the Lennox-Gastaut syndrome. In one placebo-controlled study, 33% of children
      and young adults (aged 3 to 25 years) with refractory Lennox-Gastaut syndrome had
      a reduction in seizure frequency of > or = 50% after 16 weeks of adjunctive
      lamotrigine treatment, compared with 16% of placebo recipients (p = 0.01).
      Significant reductions in seizure frequency when compared with placebo were also
      observed in patients with refractory generalised and partial seizures. The use of
      lamotrigine has also been associated with beneficial effects on cognition and
      behaviour. Adverse events associated with lamotrigine are primarily neurological,
      gastrointestinal and dermatological and are typically mild or moderate and
      transient with the exception of a potentially serious rash. Maculopapular or
      erythematous skin rash occurred in approximately 12% of paediatric patients (aged
      < 16 years) treated with lamotrigine and was the most common reason for treatment
      discontinuation. More severe forms of rash, including Stevens-Johnson syndrome,
      occasionally occurred, with a 3-fold higher incidence in children (approximately
      1%) than adults (approximately 0.3%). However, lamotrigine treatment in
      paediatric trials was generally given at higher initial doses and faster dose
      escalations than recently revised recommendations. These factors, as well as
      concomitant use of valproic acid (valproate sodium), are associated with an
      increased risk of rash. CONCLUSION: Although published clinical evidence is still
      limited in paediatric populations, lamotrigine is an effective and generally well
      tolerated broad-spectrum agent for adjunctive treatment of refractory seizures in
      children, most notably in those with Lennox-Gastaut syndrome. Results of direct
      comparisons with other antiepileptic agents are needed to determine more clearly
      the place of lamotrigine, particularly relative to newer agents, in the treatment
      of childhood epilepsy. The potential for serious rash in recipients of
      lamotrigine should also be kept in mind. Nonetheless, lamotrigine is a welcome
      addition to the available treatments for refractory childhood epilepsy,
      particularly Lennox-Gastaut syndrome.

PMID- 10946424
TI  - Hepatitis C after liver transplantation.
AB  - Hepatitis C is the most common cause of end-stage liver disease leading to liver
      transplant. The disease can recur after transplant, resulting in clinical
      hepatitis in up to 75% of patients and severe disease in approximately 7%.
      Treatment of rejection with steroid boluses and treatment of steroid-resistant
      rejection with OKT3 have both been shown to increase the incidence of recurrent
      hepatitis C. The use of OKT3 for steroid-resistant rejection is reportedly
      associated with more severe recurrence. The calcineurin inhibitors tacrolimus and
      cyclosporine have not been conclusively associated with different rates or
      severity of recurrence. Viral levels rise 10- to 15-fold after transplant and
      appear to be associated with the use of immunosuppression. Studies suggest that
      high viral levels, either pretransplant or early after transplant, may be
      associated with severe recurrent disease. Although the role of genotype is still
      unclear, genotype 1b is known to be associated with a poorer prognosis in
      nontransplanted patients and a lesser response to treatment than other genotypes.
      Furthermore, some reports suggest that after transplant, recurrent disease may
      progress more rapidly in patients with genotype 1. Treatment options after
      recurrence remain poor. Neither interferon nor ribavirin alone provides any true
      benefit. Combination therapy appears to have a better short-term outcome but may
      be poorly tolerated, and long-term benefits are unknown. Prophylaxis with
      combination therapy may be a better option but requires further study. Finally,
      retransplantation for recurrent hepatitis C is complicated not by rapid
      recurrence of disease in the new allograft but by high perioperative mortality
      that may be predicted by the presence of renal failure or sepsis preretransplant.

PMID- 10946423
TI  - Antiviral therapy for patients with chronic hepatitis C.
AB  - Several large, randomized, controlled treatment trials in persons with hepatitis
      C and ongoing hepatitis have been reported recently. These have shown that, in
      patients without other comorbid conditions, treatment for from 6 to 12 months
      with a combination of interferon-alpha 2b, 3 MU three times a week (ttw), plus
      ribavirin, 1,000-1,200 mg daily, results in a higher incidence of sustained
      virologic response than does treatment with interferon-alpha 2b monotherapy, 3 MU
      ttw, given for similar durations. Patients who have relapsed after interferon
      monotherapy may achieve a sustained virologic response when retreated with
      interferon plus ribavirin for 6 months or when given a higher dose of interferon
      for a longer duration than the initial treatment. By contrast, patients who had
      no virologic response to prior interferon monotherapy have only a small chance of
      achieving a sustained response when similarly retreated. Although the efficacy of
      treatment for hepatitis C has improved steadily over the last decade, current
      interferon-based therapies still achieve a sustained virologic response in fewer
      than half of patients who initiate therapy, are associated with appreciable side
      effects, and are expensive. Furthermore, the natural history of chronic hepatitis
      C suggests that even in the absence of therapy, most patients with chronic
      hepatitis C infection may experience little morbidity or mortality for decades.
      Finally, published therapeutic trials stem largely from tertiary referral
      centers, where an especially high level of commitment is expected from both the
      patients and the team in charge of therapy. Typically, such trials have also
      excluded patients with comorbid diseases, thus reducing their "generalizability."
      This review focuses on two fundamental questions about the currently available
      treatments for this disease: Who should be treated with them? And when should
      they be treated? Critical analysis suggests that the answers to these questions
      are not as clear as they may superficially appear.

PMID- 10946425
TI  - Vaccine development for hepatitis C.
AB  - Given the global disease burden and public health impact of hepatitis C, the
      development of an effective vaccine is of paramount importance. However, many
      challenging obstacles loom ahead of this goal. The hepatitis C virus (HCV), being
      an RNA virus, can mutate rapidly in adaptation to the environment, thus
      contributing to the high sequence divergence of multiple viral isolates in the
      world. The highest heterogeneity has been found in the hypervariable region of
      the envelope glycoprotein 2, which contains a principal neutralization epitope.
      HCV also causes persistent infection in a high percentage of immunocompetent
      hosts despite active immune response. The lack of an efficient tissue culture
      system for propagating HCV and testing neutralizing antibodies adds further
      complexity to the task of vaccine development. The immunologic correlates
      associated with disease progression or protection are yet to be defined, but
      recent studies suggest that a vigorous multispecific cellular immune response is
      important in the resolution of infection. Induction of high-titer, long-lasting,
      and cross-reactive antienvelope antibodies and a vigorous multispecific cellular
      immune response that includes both helper and cytotoxic T lymphocytes may be
      necessary for an effective vaccine. Several promising approaches have been used
      to develop an HCV vaccine. Novel vaccine candidates based on molecular technology
      such as recombinant proteins, peptides, viruslike particles, naked DNA, and
      recombinant viruses are being explored. The final vaccine product may require
      multiple components that target various aspects of protective immunity. Finally,
      sterilizing immunity may not be necessary if a vaccine can be developed to
      prevent chronic infection, which is the major cause of morbidity and mortality
      from this disease.

PMID- 10946426
TI  - A 67-year-old man with hepatitis C virus infection and a liver tumor.
AB  - A 67-year-old man with no known liver disease was found to have an incidental
      tumor in the right liver lobe. His serum liver enzyme and alphafetoprotein were
      within normal limits, but he was found to be reactive for anti-HCV. The tumor was
      an intrahepatic cholangiocarcinoma. Since the only risk factor in this patient
      was hepatitis C infection, this case appears to support the recently suggested
      role of hepatitis C virus in the development of intrahepatic cholangiocarcinoma.

PMID- 10946427
TI  - Afterword: HCV in the decades ahead.

PMID- 10946428
TI  - Cluster randomized trials in general (family) practice research.
AB  - Cluster randomized trials are increasingly common in general practice (family
      medicine). This paper will consider the design and analysis of such trials and
      emphasize the similarities and differences with trials in education, heath
      promotion and public health. Issues discussed are the estimation and range of
      values of the intra-cluster correlation coefficient found in general practice,
      and the associated sample size problems. There are problems with widely varying
      numbers of subjects per cluster, which leads to planning and analysis
      difficulties. Ethical issues in these trials, and considerations such as the
      principle of intention to treat are also considered. An example of the type of
      analysis available for a continuous outcome variable is given, and the available
      software is summarized briefly.

PMID- 10946429
TI  - Design and analysis issues in cluster-randomized trials of interventions against
      infectious diseases.
AB  - This paper discusses the application of the cluster-randomized trial (CRT) design
      to evaluate the effectiveness of interventions against infectious diseases. In
      addition to the usual rationale for this design, there are a number of other
      advantages that are peculiar to the study of infectious diseases. In particular,
      CRTs are able to measure the overall effect of an intervention at the population
      level, capturing both the direct effect of an intervention on an individual's
      susceptibility to infection, and also the indirect effects due to changes in
      risks of transmission to other individuals, or to the mass effect or 'herd
      immunity' resulting from intervening in a large proportion of the population. We
      briefly review published CRTs of interventions against infectious diseases, most
      of which have been conducted in the developing countries where such diseases
      predominate. The focus is on trials in which communities or other large groupings
      are randomized, and in which impacts on infectious disease incidence or mortality
      are assessed. We then discuss three issues that are of special relevance to CRTs
      of infectious diseases. First, issues relating to the definition and size of
      clusters; secondly, the role of matching or stratification, and the choice of
      matching factors; and thirdly, the definition of direct and indirect effects of
      intervention, and methods of assessing these components in a CRT. We conclude by
      outlining some areas for future research.

PMID- 10946430
TI  - Components of variance in a group-randomized trial analysed via a random
      coefficients model: the Rapid Early Action for Coronary Treatment (REACT) trial.
AB  - Rapid Early Action for Coronary Treatment (REACT) was a multisite trial testing a
      community intervention to reduce the delay between onset of symptoms of acute
      myocardial infarction (MI) and patients' arrival at a hospital emergency
      department. The study employed a group-randomized trial design, with ten
      communities randomized from within matched pairs to each of two conditions. REACT
      also employed continuous data collection, based on surveillance of heart attack
      patients in community emergency departments. They analysed their data by
      comparing the mean slope for delay time in the ten intervention communities to
      the mean slope estimated in the ten control communities. Because no estimates of
      slope variation were available a priori, REACT was sized using approximations
      based on more traditional designs. In this paper, we present the slope and
      residual error variances as estimated from the REACT data and examine their
      influence on the power of the trial post hoc. We also examine the power of the
      trial as it would have been given a more traditional pretest-post-test design
      with analysis via a comparison of the net difference in condition means pretest
      vs post-test.

PMID- 10946431
TI  - Analysis of dichotomous outcome data for community intervention studies.
AB  - Community intervention trials are becoming increasingly popular as a tool for
      evaluating the effectiveness of health education and intervention strategies.
      Typically, units such as households, schools, towns, counties, are randomized to
      receive either intervention or control, then outcomes are measured on individuals
      within each of the units of randomization. It is well recognized that the design
      and analysis of such studies must account for the clustering of subjects within
      the units of randomization. Furthermore, there are usually both subject level and
      cluster level covariates that must be considered in the modelling process. While
      suitable methods are available for continuous outcomes, data analysis is more
      complicated when dichotomous outcomes are measured on each subject. This paper
      will compare and contrast several of the available methods that can be applied in
      such settings, including random effects models, generalized estimating equations
      and methods based on the calculation of 'design effects', as implemented in the
      computer package SUDAAN. For completeness, the paper will also compare these
      methods of analysis with more simplistic approaches based on the summary
      statistics. All the methods will be applied to a case study based on an
      adolescent anti-smoking intervention in Australia. The paper concludes with some
      general discussion and recommendations for routine design and analysis.

PMID- 10946432
TI  - Random-effects regression analysis of correlated grouped-time survival data.
AB  - Random-effects regression modelling is proposed for analysis of correlated
      grouped-time survival data. Two analysis approaches are considered. The first
      treats survival time as an ordinal outcome, which is either right-censored or
      not. The second approach treats survival time as a set of dichotomous indicators
      of whether the event occurred for time periods up to the period of the event or
      censor. For either approach both proportional hazards and proportional odds
      versions of the random-effects model are developed, while partial proportional
      hazards and odds generalizations are described for the latter approach. For
      estimation, a full-information maximum marginal likelihood solution is
      implemented using numerical quadrature to integrate over the distribution of
      multiple random effects. The quadrature solution allows some flexibility in the
      choice of distributions for the random effects; both normal and rectangular
      distributions are considered in this article. An analysis of a dataset where
      students are clustered within schools is used to illustrate features of random
      effects analysis of clustered grouped-time survival data.

PMID- 10946433
TI  - Australian experience with the Wernicke-Korsakoff syndrome.

PMID- 10946434
TI  - Inpatient substance abuse care and the outcome of subsequent community
      residential and outpatient care.
AB  - AIM: To compare participation in treatment and 1-year substance use, symptom and
      functioning outcomes between patients with substance use disorders who did versus
      those who did not have an episode of inpatient care immediately prior to an
      episode of community residential and outpatient mental health care. DESIGN: Two
      matched groups of 257 patients each with substance use disorders were assessed at
      entry to and discharge from a community residential facility (CRF) and at a 1
      year follow-up. FINDINGS: Patients in the two treatment groups received a
      comparable amount of CRF and outpatient mental health care. Nevertheless,
      patients who had prior inpatient care were more likely to be employed at 1-year
      follow-up. In addition, when they entered CRF care directly, patients with co
      morbid psychiatric disorders were more likely to continue use of alcohol and
      drugs in the CRF and less likely to complete the program. These patients also
      experienced more distress and psychiatric symptoms, and were less likely to be
      employed at the 1-year follow-up. CONCLUSIONS: Among patients who seek treatment
      at Department of Veterans Affairs (VA) facilities, those who have both substance
      use and psychiatric disorders and enter CRF care directly have somewhat worse
      outcomes than those who have an immediately prior episode of inpatient care.

PMID- 10946435
TI  - Evaluating theories of alcohol-related aggression using observations of young
      adults in bars.
AB  - AIMS: The objective of the present study is to evaluate 36 explanations of
      alcohol-related aggression that have been proposed in the research literature in
      terms of their relevance to naturally-occurring incidents of aggression involving
      alcohol. DESIGN: The study involved content analysis of descriptions of 105
      incidents of aggression. SETTING AND PARTICIPANTS: Bars frequented by young
      adults. MEASUREMENTS: Step-by-step descriptions of incidents of aggression
      reported by researcher-observers based on 93 nights of observation in bars
      between midnight and 3 a.m. FINDINGS: Some explanations relating to the effects
      of alcohol (e.g. focused on the present, reduced anxiety about sanctions or
      danger, heightened emotionality) and the environment (e.g. generally permissive
      environment, expectation by patrons that aggression will be tolerated) were found
      to be relevant to most incidents, while other explanations (e.g. crowding,
      release of pent-up anger) were directly relevant to only a few or no incidents.
      Incidents involving male-to-male aggression were more likely than incidents
      involving both males and females to be attributable to expectations, acceptance
      of aggression, power concerns, male honor and "macho" values. Principal
      components analysis identified five groupings of explanations: risk-taking
      effects of alcohol, cognitive impairment from alcohol, hyperemotional effects of
      alcohol, "macho" subculture, and permissive environment. CONCLUSIONS: The
      findings are consistent with a model of alcohol-related aggression that involves
      multiple contributing factors including alcohol effects and situational contexts.
      The greater relevance of certain explanations and the natural groupings of
      explanations point to directions for future research.

PMID- 10946436
TI  - Drinking patterns and health outcomes: occasional versus regular drinking.
AB  - AIMS: To compare the health of drinkers with different drinking patterns and
      particularly drinkers with comparable average intakes and different drinking
      frequency. SETTING: General population survey conduced in Eindhoven, the
      Netherlands (n = 18,973). MEASUREMENTS: Chronic conditions, perceived general
      health, and health complaints were the outcome measures. Drinking categories were
      constructed by taking into account the frequency and amount of alcohol
      consumption (up to six glasses per sitting). FINDINGS: Drinking 3-5 days per
      week/3-5 glasses per occasion and drinking 6-7 days/1-2 glasses were associated
      with lower likelihood for reporting health complaints and for perceiving one's
      health as less than good compared to those drinking 1-2 days/1-2 glasses
      (reference group). Drinking 1-2 days/6 glasses was associated with being more
      likely to report chronic conditions, compared to the reference group. Those
      drinking 1-2 days/6 glasses were significantly more likely to report > 3 health
      complaints than those drinking 6-7 days/1-2 glasses. Although no differences were
      observed for any of the other comparison groups, at high levels of consumption
      (18-35 units/week), occasional drinkers (3-5 days/6 glasses) seemed to have
      better health outcomes compared to their counterparts (6-7 days/3-5 glasses).
      CONCLUSION: In addition to average alcohol intake, drinking pattern is also
      related to health.

PMID- 10946437
TI  - Personality disorder traits, family environment, and alcohol misuse: a
      multivariate behavioural genetic analysis.
AB  - AIMS: This study seeks to estimate the extent to which a common genetic and
      environmental basis is shared between (i) traits delineating specific aspects of
      antisocial personality and alcohol misuse, and (ii) childhood family
      environments, traits delineating broad domains of personality pathology and
      alcohol misuse. DESIGN: Postal survey data were collected from monozygotic and
      dizygotic twin pairs. SETTING: Twin pairs were recruited from Vancouver, British
      Columbia and London, Ontario, Canada using newspaper advertisements, media
      stories and twin clubs. PARTICIPANTS: Data obtained from 324 monozygotic and 335
      dizygotic twin pairs were used to estimate the extent to which traits delineating
      specific antisocial personality traits and alcohol misuse shared a common genetic
      and environmental aetiology. Data from 81 monozygotic and 74 dizygotic twin pairs
      were used to estimate the degree to which traits delineating personality
      pathology, childhood family environment and alcohol misuse shared a common
      aetiology. MEASUREMENTS: Current alcohol misuse and personality pathology were
      measured using scales contained in the self-report Dimensional Assessment of
      Personality Pathology. Perceptions of childhood family environment were measured
      using the self-report Family Environment Scale. FINDINGS: Multivariate genetic
      analyses showed that a subset of traits delineating components of antisocial
      personality (i.e. grandiosity, attention-seeking, failure to adopt social norms,
      interpersonal violence and juvenile antisocial behaviours) are influenced by
      genetic factors in common to alcohol misuse. Genetically based perceptions of
      childhood family environment had little relationship with alcohol misuse.
      CONCLUSIONS: Heritable personality factors that influence the perception of
      childhood family environment play only a small role in the liability to alcohol
      misuse. Instead, liability to alcohol misuse is related to genetic factors common
      a specific subset of antisocial personality traits describing conduct problems,
      narcissistic and stimulus-seeking behaviour.

PMID- 10946438
TI  - Reactivity to alcohol-related stimuli in the laboratory and in the field:
      predictors of craving in treated alcoholics.
AB  - AIMS: (1) To search for predictors of alcohol craving in treated alcoholics; (2)
      to evaluate the relationship between craving and drinking immediately after
      treatment. DESIGN: Alcoholic patients in treatment underwent cue-reactivity
      trails in the laboratory and then recorded craving in the field using hand-held
      computers. Laboratory craving was correlated with craving in the field, and moods
      and situations recorded in the field were correlated with contemporaneous craving
      ratings using a multi-level correlational design. SETTING: A VA Medical Center
      substance abuse treatment program provided the treatment and laboratory settings.
      The patients' home environment was the field setting. PARTICIPANTS: Male alcohol
      dependent veterans (N = 26) treated in a VA inpatient or intensive outpatient
      program. INTERVENTION: Participants underwent two cue-reactivity laboratory
      sessions prior to discharge to measure craving. Following discharge, participants
      recorded drinking and cravings eight times per day for 21 consecutive days.
      MEASUREMENTS: Craving ratings in the laboratory and multiple recordings per day
      of surroundings, craving and mood state in the field. FINDINGS: Desire to drink
      in the laboratory accounted for 8-10% of the variance in later drinking and urges
      to drink recorded in the field--a modest correlation. Frequency of positive urges
      in the field was significantly correlated with drinking frequency. Those who
      reported urges in the field had greater alcohol dependence and higher trait anger
      and anxiety scores than non-reporters. CONCLUSIONS: Craving is related to
      drinking immediately following treatment, and is most likely in those who have
      more severe dependence and greater mood disturbance. These individuals may
      benefit most from interventions for coping with cravings after treatment.

PMID- 10946439
TI  - Development and validation of a scale measuring self-efficacy of current and
      former smokers.
AB  - AIMS: To develop and test the validity of a questionnaire measuring the
      confidence of current and former smokers in their ability to abstain from smoking
      in high-risk situations. DESIGN AND PARTICIPANTS: We collected qualitative data
      in a first mail survey in 115 smokers and ex-smokers, and used these data to
      develop survey items. We collected quantitative data in a second mail survey in
      529 smokers and ex-smokers to finalize the instrument. SETTING: General
      population in Geneva, Switzerland, 1995, 1997 and 1998. FINDINGS: The study
      resulted in a two-dimensional 12-item scale: the "Smoking Self-Efficacy
      Questionnaire" (SEQ-12). The two six-item subscales measure confidence in ability
      to refrain from smoking when facing internal stimuli (e.g. feeling depressed) and
      external stimuli (e.g. being with smokers). Internal consistency coefficients
      were high ("internal stimuli": alpha = 0.95; "external stimuli": alpha = 0.94).
      Test-retest intraclass correlation coefficients were high (0.95 and 0.93 for the
      two scales, respectively). In smokers, baseline self-efficacy scores predicted
      smoking cessation at 16-month follow-up. Finally, the scale respected criteria of
      content- and construct validity. CONCLUSION: SEQ-12 is a valid and reliable
      scale, which has applications in both research and clinical settings. It can also
      produce input data for computer systems that generate counselling reports
      tailored to the characteristics of each individual smoker.

PMID- 10946440
TI  - Comparing the predictive validity of DUI risk screening instruments: development
      of validation standards.
AB  - AIMS: This study compares the predictive efficacy of driving under the influence
      (DUI) screening instruments validated in previous studies, illustrates how
      variations in base rates of failure and selection ratios affect conclusions
      concerning the efficacy of different instruments, and develops evaluation
      standards to ensure valid comparisons of risk prediction instruments. DESIGN: The
      study: (1) examines a sample of 4815 DUI offenders to illustrate how variations
      in base rates of failure and selection ratios affect traditional measures of
      predictive efficacy, (2) uses such measures to compare the predictive efficacy of
      10 instruments validated in previous studies, and (3) demonstrates the use of a
      measure of predictive efficacy which is relatively insensitive to the
      aforementioned variations. FINDINGS: While three instruments examined at specific
      cut-points consistently ranked highest on several measures of predictive
      efficacy, use of different evaluation standards produced substantively different
      conclusions regarding the efficacy of different instruments. Based on the
      analyses, standards for validation of risk prediction instruments were developed.
      CONCLUSIONS: The findings illustrate how failure to use equivalent standards have
      led to erroneous conclusions concerning the relative predictive efficacy of
      different risk prediction instruments. The standards developed in this study
      should facilitate equivalent comparisons of the predictive efficacy of risk
      prediction instruments.

PMID- 10946441
TI  - Factors associated with injecting risk behaviour among serial community-wide
      samples of injecting drug users in Glasgow 1990-94: implications for control and
      prevention of blood-borne viruses.
AB  - AIMS: To examine the association between recipient-sharing of needles and
      syringes and demographic characteristics, injecting behaviour and needle and
      syringe exchange utilisation. DESIGN: Self-report data from serial cross
      sectional surveys. SETTING: Multiple street, needle and syringe exchange and drug
      treatment sites throughout Glasgow. PARTICIPANTS: 2576 current injecting drug
      users (IDUs) recruited during 1990-94. FINDINGS: In the multiple logistic
      regression analysis, a significantly lower level of recipient-sharing was
      associated with respondents who resided within 1 mile of a needle and syringe
      exchange compared to those who lived further away (adjusted OR 1.3; 95% CI 1.0
      1.6), and by IDUs who reported obtaining either 6-15, 16-30, or > 30 sterile
      needles and syringes in an average week from a needle exchange and/or pharmacist
      (adjusted ORs 0.55, 0.34, 0.25; 95% CIs 0.3-0.9, 0.2-0.6 and 0.2-0.4,
      respectively) compared to those who obtained no sterile equipment from these
      sources. Recipient-sharing of needles and syringes in the previous 6 months
      reduced significantly between 1990 (43%) and 1991-94 (27-33%) (p < 0.0001); this
      decline was not explained by needle and syringe exchange utilization, suggesting
      that additional factors were influencing behavioural change at that time.
      CONCLUSION: Our data indicate that improving injectors' convenience of access to
      exchange facilities and increasing the numbers of sterile needles and syringes
      available to them is likely to result in further reductions in recipient-sharing,
      and thus the potential for blood-borne virus transmission, among IDUs.

PMID- 10946442
TI  - Ten-year survival analysis of a cohort of heroin addicts in Catalonia: the
      EMETYST project.
AB  - AIMS: To determine mortality rates and immediate causes of death in a cohort of
      heroin addicts, and to compare them with other European samples. DESIGN:
      Longitudinal follow-up study of a cohort for 10.5 years (March/July 1985-December
      1995). SETTING: Catalonia, Spain. PARTICIPANTS: One hundred and thirty-five
      heroin addicts. MEASUREMENTS: (a) Number of total and annual events; (b) annual
      mortality rate; (c) average annual mortality rate; and (d) standardized mortality
      ratio (SMR). Kaplan-Meier (log rank test) was used to assess the predictive
      factors. FINDINGS: During this period, 41 heroin addicts died (30%), the average
      annual mortality rate was 3.4% and the SMR was 28.5. The most frequent causes of
      death fell in ICD-9 chapter III (which includes AIDS) (51%) and in chapter XVII
      (which includes overdose) (30%). Neither the socio-demographic characteristics
      nor the history of heroin consumption were predictors of survival or cause of
      death. CONCLUSIONS: Compared to other European studies, the cohort in the EMETYST
      project has the highest SMR and members have a higher chance of dying due to
      AIDS. The predictors of survival in the long term must be interpreted with
      caution, with the exceptions of being HIV positive or being diagnosed with AIDS.

PMID- 10946443
TI  - Medical education in substance-related disorders: components and outcome.
AB  - AIMS: To analyze the process of acquisition by physicians of a body of knowledge
      and skills in the management of substance abuse. DESIGN: A comprehensive search
      of English-speaking literature was conducted over 20 years. Articles assessing
      the outcome of educational strategies in undergraduate, graduate and continuing
      medical education were examined to determine the targeted sample, the educational
      strategies involved and the outcomes assessed. FINDINGS: Nine studies in
      undergraduate education, 11 in graduate and 11 in continuing education met the
      inclusion criteria. They were generally difficult to compare in design, strategy
      and outcome analysis. Cognitive knowledge and behavioral skills appear to be
      easier to obtain compared to more complex attitudinal shifts. CONCLUSIONS: There
      is growing consensus in the selection of a combined didactic and interactive
      educational strategy but few empirical data as to the more cost-effective
      learning interventions. Training must be reinforced at regular intervals. While
      the expanding panoply of interventions available to physicians should enhance the
      perceptions of role legitimacy and treatment optimism, cohort studies across
      levels of education, specialty groups and across-substance and other addictive
      behaviors are required to determine cost-effective educational strategies.

PMID- 10946444
TI  - Prevalence of excessive gambling before and after introduction of a national
      lottery in the United Kingdom: another example of the single distribution theory.
AB  - BACKGROUND: According to the single distribution theory advocated by Rose, the
      prevalence of a deviant condition such as excessive alcohol consumption depends
      upon the average level of the corresponding characteristic in the population. The
      objective of this study was to establish whether the single distribution theory
      applies to gambling behaviour. METHODS: Household gambling expenditure in the
      United Kingdom was examined using Family Expenditure Survey data collected before
      and after the introduction of a national lottery in November 1994. RESULTS: In
      cross-sectional analyses, the mean (or median) household expenditure on gambling
      for each region predicted the prevalence of excessive gambling in that region:
      the slope of the relationship in 1995-96 was equivalent to an increase of 1.2
      (95% CI 0.7-1.7) points in the percentage of households gambling more than 10% of
      income for every increase of 1 Pound in mean household gambling expenditure. The
      introduction of the national lottery was associated with an increase in mean
      household gambling expenditure from 1.45 Pounds to 3.81 Pounds per week, and an
      increase in the proportion of households gambling more than 10% of total income
      four-fold from 0.4% to 1.7%. Among households with income of less than 200
      Pounds/week, the proportion gambling more than 10% of their income increased from
      0.6% to 3.2%. INTERPRETATION: The single distribution theory applies to gambling
      behaviour. The increase in average gambling expenditure associated with the
      introduction of a national lottery in the United Kingdom has led to a pronounced
      increase in the prevalence of excessive gambling, especially in low-income
      households. This is likely to increase the prevalence of gambling disorders and
      to exacerbate social inequalities in health.

PMID- 10946445
TI  - The Immunization Monitoring Program-active (IMPACT) prospective surveillance of
      varicella zoster infections among hospitalized Canadian Children: 1991-1996.

PMID- 10946446
TI  - What is the appropriate initial dose of corticosteroids to treat giant cell
      arteritis?

PMID- 10946447
TI  - Maximizing antihypertensive management in the elderly.
AB  - The management of hypertension in the elderly is safer and more effective if we
      consider diurnal fluctuations in blood pressure, preexisting postural and
      postprandial hypotension, and coronary risk when setting therapeutic goals and
      selecting or adjusting antihypertensive medications. Lifestyle modifications
      should coincide with drug therapy in the management of elderly hypertensive
      patients. The author suggests a checklist of specific considerations when
      treating hypertension in the elderly.

PMID- 10946448
TI  - Palliative medicine: old dogs and new tricks.
AB  - In palliative medicine, many older drugs can be used for off-label indications,
      either to augment the action of approved drugs or to substitute for approved
      drugs that fail to provide relief.

PMID- 10946449
TI  - In cholesterol lowering, moderation kills.
AB  - The high-fat American diet is responsible for an epidemic of coronary artery
      disease. A plant-based diet with less than 10% fat will prevent coronary disease
      from developing, halt the progress of existing disease, and even reverse the
      disease in many patients. Given proper support and education, motivated patients
      with a history of coronary disease can follow this diet and prevent future
      cardiac events.

PMID- 10946450
TI  - Of rice, grain, and zeal: lessons from Drs. Kempner and Esselstyn.

PMID- 10946451
TI  - Update on antiviral therapy for genital herpes infection.
AB  - For the primary infection of genital herpes, antiviral therapy with acyclovir is
      the gold standard. For recurrences, there are two options: antiviral treatment of
      each outbreak as it arises, or suppression of outbreaks with daily oral therapy.
      Patients tend to prefer the latter because it can decrease the number and
      severity of outbreaks, but it increases asymptomatic viral shedding and,
      therefore, the risk of unwittingly transmitting herpes simplex virus to
      uninfected sexual partners.

PMID- 10946452
TI  - Fibrinolytic therapy in the elderly: making sense of troubling new findings.

PMID- 10946454
TI  - Regional delivery of anticancer drugs: current applications.
AB  - For cancers that remain confined to a specific region through most of their
      course, one treatment option is to deliver anticancer drugs directly to that
      region. Clinical experience shows that regional delivery can palliate symptoms,
      improve quality of life, and prolong survival. However, whether it increases the
      cure rate remains controversial, and it is costly because of the need to
      surgically implant infusion devices.

PMID- 10946453
TI  - New options for untreatable coronary artery disease: angiogenesis and laser
      revascularization.
AB  - Some patients with severe symptomatic coronary artery disease despite maximal
      medical therapy are not eligible for bypass surgery or percutaneous coronary
      intervention, but may be eligible for two newer therapies: therapeutic
      angiogenesis with growth factors and transmyocardial laser revascularization.

PMID- 10946455
TI  - Rosacea: an update.
AB  - Rosacea is a common inflammatory skin disease affecting the central face of
      adults. Its etiology is unknown. Early diagnosis and appropriate treatment,
      usually with topical or systemic antibiotics or both, minimizes symptoms and
      helps to prevent complications.

PMID- 10946456
TI  - Long-term outcomes excellent for atrial septal defect repair in adults.
AB  - Congenital atrial septal defect repair is safe and effective in patients of
      almost any age. Long-term survival among adults is excellent, although children
      generally appear to fare even better. Our 25-year study of outcomes among adults
      who underwent suture or patch closure found that survival exceeded 90%. We
      discuss our observations on use of transesophageal echocardiography, indications
      for cardiac catheterization, and continuing questions about atrial septal defect
      in adults.

PMID- 10946457
TI  - Interferometry in the assessment of biomechanical features of the masticatory
      system hard segments.
AB  - Biomechanical studies have found wide application and solved many problems in
      dental medicine. An interdisciplinary approach has allowed an ever-faster
      progress in the field. The aim of this study was to point out the advantages of
      holographic interferometry. With the use of this method, the study object is
      observed as a whole rather than as a substrate, thus providing a three
      dimensional holographic image visualizing the load transmission from one jaw to
      another, tooth pressure against the alveolus, and strain of Sharpey's fibers, and
      yielding precise data on deformities, dislocations and force distribution.

PMID- 10946458
TI  - Mandibular border positions in eugnathic subjects during the second bite lifting.
AB  - This research was aimed at performing a clinical functional analysis during the
      second bite lifting, in order to define mandibular border positions and possible
      differences by sex and/or age. Out of a total of 9680 examined children from the
      region of Medimurje, Croatia, 103 were found to be eugnathic, with dentition in
      occlusion during the phase of the second bite lifting. All the eugnathic patients
      belonged to the class I by Angle, without any caries, fillings or extracted
      teeth. They were divided into three predefined groups for the sake of comparison.
      The obtained values of mandibular border positions in eugnathic subjects during
      the second bite-lifting phase vary with age and with the number of present
      permanent teeth in occlusion. Generally, all the values are higher in girls than
      in boys, which speaks in favour of the assumption that mandibular border
      positions are determined by sex, hormonal activity, growth and intercuspidation.
      Also, girls show a higher TMJ flexibility as well as a higher mandibular
      mobility. The knowledge of these facts will contribute to a more precise
      treatment in child prosthetics and pedodontics.

PMID- 10946459
TI  - Model for computer simulation of bone tissue.
AB  - The paper deals with the dependence of the torsional moment on the angle of the
      compact bone torsion in laboratory animals and humans. Based on the data for
      laboratory animals obtained by measurements, the data on dependence of the
      torsional moment and the angle of torsion were predicted for humans. The
      measurements were carried out in four groups of laboratory animals. One was the
      control group, and the other three groups were treated by various vitamin D3
      metabolites. The same measurements were performed also in only one group of
      humans, due to the impossibility to treat humans with vitamin D3 metabolites. The
      functional relationship between the angle of torsion and the torsional moment for
      all the groups of animal bone tissue were determined by measurements, and results
      were used to predict the reaction of the human compact bone tissue if treated by
      vitamin D3 metabolites.

PMID- 10946460
TI  - Trends in dental caries in 12-year old children in Croatia.
AB  - In this epidemiological study the caries status of 12-year-old children was
      compared over time for the years 1968, 1973, 1980, 1985, 1990, 1991 and 1999. The
      mean number of decayed, missing and filled teeth (DMFT) decreased from 7.0 in
      1968 to 2.6 in 1991. From 1991 to 1999 and increase of DMFT 2.6 in 1991, to 3.5
      in 1999) has been seen which is result of war in Croatia and reorganisation of
      health care delivery system. With the expected continuing decline in the
      prevalence and severity of oral diseases, one of the main problems in the future
      seems to be the transition of the oral health care delivery system from a disease
      oriented system to a health-oriented one.

PMID- 10946461
TI  - The patient's and the therapist's evaluation of bridges of different materials
      and age.
AB  - The aim of this study was to find out patients' satisfaction with their bridges
      made of different materials (metal-ceramics, Au/resin, Ag-Pd/resin). One hundred
      and sixty four patients were examined at the Dental School, University of Zagreb,
      Croatia. They assessed their bridges--the overall quality, aesthetics, speech,
      chewing and the health of the gingiva by the scale from 1-5. The same categories
      were also assessed by a trained prosthodontist. The majority of the patients was
      really satisfied and gave the highest grades (quality, aesthetics, speech, etc.)
      and therefore the results were skewed and asymmetrical towards the biggest scores
      (biggest grades). The best gingival health was evaluated by the group of patients
      with ceramic crowns and bridges (p < 0.05) and the worst by the patients with Ag
      Pd bridges. Speech was scored higher for the lateral than for the frontal
      bridges. Patients evaluated the health of the tissue surrounding their bridges,
      overall quality of fixed prosthodontic appliance and aesthetics with
      significantly higher scores than the prosthodontist (p < 0.01). The results point
      at a difference between the patient's and the therapist's evaluations and to the
      patient's insufficient care about the gingiva around the bridge abutments.

PMID- 10946462
TI  - Evaluation of craniometric methods for determination of vertical dimension of
      occlusion.
AB  - In clinical practice, fully precise method for exact determination of vertical
      relation of occlusion still does not exist. This study examines the relationship
      between different craniofacial distances and the distance subnasale-gnathion (Sn
      Gn), which represents the lower third of the face in vertical relation
      determination. The highest coefficient of correlation was (r = 0.8678, p < 0.05)
      between the distance eye-ear (E-E = lateral border of the ocular orbit-medial
      opening of the meatus of the external auditory canal) and Sn-Gn. The prediction
      of the distance Sn-Gn could be determined through the formula: Sn-Gn = E-E/1.08
      or through the regression analysis: Sn-Gn = 1.9197 + 0.6449 x E-E. None of the
      calculated coefficients of correlation was 1, but was < 1, so that the prediction
      of the distance Sn-Gn by craniometric distances is not absolutely reliable,
      although it is considerably helpful. Our results point at the variations of
      craniofacial distances in the Croatian population. Yet, craniometry could still
      be recommended in everyday clinical practice for prediction of vertical relation
      of occlusion, as it is a simple, economic and non-invasive method, however in
      combination with some other methods, which have proved to be helpful.

PMID- 10946463
TI  - The effect of tooth loss on the TM-joint articular eminence inclination.
AB  - The inclination between the posterior wall of the articular eminence and the
      referential plane (Frankfurt line) was measured on 137 dry skull specimens (78
      with complete dental arches and 59 edentulous). Both left and right joints were
      measured using direct craniometric method. The results were compared with respect
      to the loss of teeth, side and sex. A large range of measured values of the
      eminence inclination shows great individual differences, so that the mean values
      can have only orientational significance. The mean value of eminence inclination
      for all measured specimens was 61.9 angular degree. The difference between the
      two groups established upon dental status is very small and without any
      statistical significance (P > 0.05). The right joint shows a slightly steeper
      eminence inclination compared to the left one, but without any statistical
      significance (P > 0.05). Asymmetry between the right and left joint appears
      almost as a rule, while maximum measured differences reach up to 33 degrees, with
      mean absolute difference of 6.9 degrees. The group of edentulous specimens shows
      a greater symmetry and less differences between the left and right joint, which
      indicates that different bimechanical conditions in the joint, due to tooth loss
      might lead to remodellation of the articular eminence. The eminence inclination
      was significantly steeper in male specimens in all subgroups (P < 0.001), which
      confirms sexual dimorphism.

PMID- 10946464
TI  - Dynamic effects of food consistency on chewing motions.
AB  - The purpose of the study was to find evidence of how different types of food
      consistency affect chewing motions, especially the forward, downward and sidewise
      extents of motion of the lower jaw. Nineteen individuals with intact tooth
      sequence, aged from 20 to 37 years, were asked to chew three types of food of
      different consistency (banana, bread, carrot). The motions of the lower jaw were
      recorded by ELITE system, i.e. the measurement instrument that by stereo-photo
      grametric procedures calculates space co-ordinates of markers on faces of the
      study subjects. The system enables continuous recording of lower jaw motions in
      three dimensions, without any possibility of the study subjects' influencing the
      operation of the instrument, which significantly decreases the possibility of
      error. Study results have shown that in all 19 subjects a greater food
      consistency increases the extent of chewing motion. In each individual study
      subject different average values were found for equal shifts of lower jaw when
      chewing the same type of food. Although varying from subject to subject, the
      chewing cycle depends to a great extent on food consistency. By increasing the
      consistency of a bite, the extent of lower jaw motion has increased in every
      single study subject.

PMID- 10946465
TI  - Distribution of craniofacial variables in south Dalmatian and middle Croatian
      populations.
AB  - The objective of the present work was to determine some relevant craniofacial
      parameters, particularly in relation to sex, for the study of the distribution of
      basic head and face types, and to investigate craniofacial and morphological
      differences between two population samples. The study sample comprised 100
      subjects of both sex aged 18 to 30 from South Dalmatia and 200 subjects from
      Middle Croatia. Eight basic craniofacial variables were measured to obtain head,
      forehead and face indexes. The data indicate that average values of all variables
      can be used as standard craniofacial parameters for the examined population
      groups. All the craniofacial variables are considerably higher in men than in
      women (p < 0.05). In the South Dalmatian population mesocephalia (48.0%) and
      leptoprosopia (82.0%) prevail, while in the Middle Croatian population the
      brachycephalia (62.0%), and euriprosopia (73.5%) are present to a greater degree.
      The most significant craniofacial and morphological differences between the
      examined study samples are head width (Eu-Eu), face width (Zy-Zy), and forehead
      height (Tr-N). They were found to be statistically significant in the examined
      Middle Croatian population (p < 0.05). The presented measurements are highly
      relevant to orthodontic diagnostics and therapy.

PMID- 10946467
TI  - Orofacial analysis on the Adriatic Islands: 1. The island of Hvar as a model for
      odontogenetic researches.
AB  - This paper presents a preliminary orofacial analysis of a subadult population of
      Hvar, a Croatian island in the Adriatic. Its population represents one of the
      last genetic isolates in Europe and has therefore been the object of intensive
      crossdisciplinary research over the last 30 years. We focussed on the coefficient
      of endogamy on the one hand and malocclusal-related caries on the other hand, and
      expected differences in the latter between subgroups of the population. We
      analyzed 224 dental casts from children all over the island and found multiple
      caries in approximal surfaces in 55 percent of the children, but no significant
      differences between the subpopulations. Instead, significantly more caries
      affection was found in the boys than in the girls. The percentage of general
      caries affection is fairly high, even when compared to other isolated
      populations; it may be due to environmental influence. This would be consistent
      with the other results, which have putatively been caused by complex
      environmental influences and not solely by genetic components.

PMID- 10946466
TI  - Kineziographic research of patients with cross bite.
AB  - The paper describes the use of an objective method for the quantitative analysis
      of the relationship between the posterior cross-bite and the occurrence of
      occlusive interferences and damages to the mandible muscle elevator. Two groups
      of subjects were selected for the analysis: 10 patients with unilateral cross
      bite and 10 students without any symptoms of temporomandibular disorders (TMD).
      By means of the Robert Jenkelson K5A kinesiograph we measured maximal opening
      velocity of the mandible (mm/s), maximal-closing velocity (mm/s), first tooth
      contact velocity and displacement in the vertical plane at the maximal
      intercuspidation (mm). The following values were obtained: maximal-opening
      velocity in the first group was 349 mm/s and 380 mm/s in the control group. This
      difference was incidental. The maximal closing velocity in the study group was
      204.9 and 345.2 in the control group (p < 0.05). The first tooth contact velocity
      in the study group was 75.93 and 325 in the control group (p < 0.01).
      Displacements in the vertical plane at the maximal intercuspidation in the
      investigated group was 0.24 +/- 0.01 mm, while in control group that value was
      0.12 +/- 0.012 mm.

PMID- 10946468
TI  - The patient's and the therapist's evaluation of complete denture therapy.
AB  - A total of 222 patients were studied. In a questionnaire patients graded their
      complete dentures of different age and quality, depending on the level of
      satisfaction, using the modified analogue-visual scale from 1 to 5. The dentist
      assessed the same dentures, as well as the denture bearing area. The patients'
      assessments were surprisingly high, the grades were bigger than the therapist's
      (p < 0.05), but in disappointed patients the grades were smaller than the
      therapist's (p < 0.05). It seems that the dentist is more critical in assessments
      than the patient. No significant difference existed between chewing and denture
      stability and between stability and the comfort of wearing lower full denture (p
      > 0.05). Unstable denture aggravates chewing and causes pain and discomfort on
      the bearing area. It seems that subjective factors in patients, expectations of
      the denture or the number of previous dentures play a role in satisfaction, not
      only the quality of denture bearing area and the quality of a denture.

PMID- 10946469
TI  - Hereditary and environmental dental findings in identification of human remains.
AB  - The paper presents the results on hereditary and environmental dental findings in
      identification of human remains exhumed from mass graves in the Republic of
      Croatia. The total of 17,880 teeth from all the categories (incisors, canines,
      premolars and molars) was examined. Hereditary findings of the teeth such as
      shape, size, position, as well as age were used in all of the cases confirming
      and completing the identification. In only 15% of the cases they were the
      starting points for the identification that would be later confirmed with another
      3-5 traditional identification procedures. Disturbances in tooth eruption were
      recorded in 22% of the cases, impaction of teeth in 10%, and retarded eruption of
      teeth in 12%. Disturbances of tooth position were recorded in 65% of the cases.
      Tooth rotation in 26% and diastema mediana in maxilla or mandible in 39%.
      Disorders of tooth number in the form of unilateral and bilateral missing of
      lateral maxillary incisors were recorded only in 2% of the monitored cases.
      Abnormalities of the tooth shape were found in 11% of the cases. The majority of
      them were found on the tooth crowns 6%, and less on the tooth roots 5%.
      Environmental dental findings that were the most significant for the
      identifications were prosthetic appliances in 30% of cases. Prostheses were
      helpful in the identification of 3% of the cases, while crowns and bridges were
      helpful in 27% of the cases. Ante mortem teeth extractions were helpful in 25% of
      the cases. Teeth restorations were recorded in 20% of the identified cases,
      amalgams in 19% and aesthetic filings in 1%. Dental caries was helpful in only
      10% of the cases, superficial caries in 3% and caries of dentin in 7% of cases.

PMID- 10946470
TI  - Measurement of magnetic field in dentistry.
AB  - The principal objective was to measure the magnetic fields occurring in dental
      surgeries at simultaneous subtraction of direct ground component of the magnetic
      field. A specifically designed instrument with the Hall probe was used for the
      measurement. It consisted of two amplifiers and a low frequency filter. Its task
      was to measure mean square values of the field (RMS) dependent on the position in
      space. Qualitative and quantitative analyses of the investigated variables
      enabled making conclusions about the magnetic fields in dental surgeries. A
      number of studies have shown that many dental instruments produce radiation with
      magnetic field higher than 40 G, at a significant decrease in power of the
      magnetic field with increasing distance from the source. It has also been
      reported that instruments of older generations produce stronger magnetic fields
      than do the new ones.

PMID- 10946471
TI  - Implant failure: regional versus cumulative evaluation.
AB  - In this paper the success rate of implant therapy in various bone regions is
      discussed. The objective is to determine whether differences existed in success
      rates of cylinder implants placed in different areas in the both maxilla and
      mandible. Forty four patients have been treated and reviewed five years after the
      placement of the fixed prosthetic restoration. The patients were provided with a
      total of 92 implants. Results from this study show very low survival rate for
      implants placed in anterior region of maxilla (55.6%) after five years. It is
      concluded that simple cumulative follow up studies do not entirely correspond to
      actual situations, positioning the implants has an important role in the planning
      of the implant therapy and that important factor for force compensation is not
      only the surrounding bone density, but also the region of the jaw where the
      implants are placed.

PMID- 10946472
TI  - Three dimensional model of the human mandible.
AB  - A new biomechanical three-dimensional (3D) model for the human mandible is
      proposed. A simple two-dimensional model cannot explain the biomechanics of the
      human mandible, where muscular forces through occlusion and condylar surfaces are
      in a state of dynamical 3D equilibrium. All forces are resolved into components
      according to a selected coordinate system. The muscular forces, which during
      clenching act on the jaw, along with the necessary force level for chewing, also
      act as some kind of stabilizers of the mandibular condyles preventing dislocation
      and loading of nonarticular tissues.

PMID- 10946473
TI  - Balint groups as a driving force of ego development.
AB  - This paper gives an overview of one of the main components in the process of
      Balint groups. The paper is based on the authors' research on the work of Balint
      groups and the study of literature which deals with the development of ego and
      the role of Balint groups in the development of participants' ego. This field is
      of great interest to the Balint movement and education in medicine. The special
      place in the discussions on the Balint method is given to the issue of benefit
      and the nature of influence of the Balint groups on participants. The Balint
      movement is of special interest for Croatia since it was perhaps among the first
      in the world to introduce Balint seminars as an official part of education of
      family doctors. The Croatian Society of Balint Groups as early as in 1970's
      became a part of the International Federation of Balint Groups. Professor
      Betlheim was Michael Balint's friend and his followers introduced the method not
      only in medicine but also in other professions: social work, pedagogy,
      psychology, sociology etc. The Balint's method is also very interesting and
      useful to stomatologists, orthopedists and physiotherapists. Croatian dentists
      joined the Balint Groups in 1983 and orthopaedists in 1987. These were the unique
      cases in the European context. The Balint groups are very efficient and necessary
      in the process of strengthening ego and selfawareness of these professionals. The
      paper also discusses the increase of the doctor's self-awareness and self
      consciousness during the process of training in the Balint Groups. The Balint
      Groups only insist on the doctor-patient relationship and do not interfere with
      the unconscious of the doctor's preoccupations. The approach of Enid Balint
      strives to find harmony between the Balint's approach and the psychoanalytic
      approach to the object of the research. According to her understanding, the
      development of the group atmosphere is similar to the one in the family. The
      authors reach a similar conclusion in their research.

PMID- 10946474
TI  - Family relationships in prediction of ageing.
AB  - This paper presents a study of the predictive value of family relationships from
      genealogies, and its impact on the delayed ageing. The study comprised adult
      population over 18 years of age of two urban family practices (N = 1700). The
      study sample included all patients (total = 581; 57.3% female, 42.7% male) having
      sought medical assistance of any kind in the period of three consecutive months.
      The study was performed in two stages. The selection of patients according to the
      results of the 25th and 75th percentiles of the memory component analysis was
      done in stage I. The comparison of life history and events across a genealogy in
      the groups of the 25th and 75th percentile memory deficit was done in stage II.
      The method used in stage I was a psychological test--Pictures of Object Test
      (POT) to test the memory deficit. In stage II, personal life histories and
      description of the genealogies were obtained by individuals' associations
      expressed in the form of a free text which was then analyzed statistically (SPAD
      T), and the results were correlated to data read on the developed genogram. The
      statistical text analysis of life-events recall and the correlation across a
      genealogy showed a difference in the patterns of family relationships across a
      genealogy in the two study groups, and their predictive value for prevention in
      family practice.

PMID- 10946475
TI  - Psychogenic factors in the aetiology of stomatopyrosis.
AB  - This research has been conducted on the basis of the association between a
      psychogenic factor and stomatopyrosis as its consequence. Stomatopyrosis is
      characterized as a burning sensation or as pain in the mouth cavity with
      clinically normal oral mucosa. It typically occurs with elderly female
      population, aged on average 67. Burning mouth as a symptom occurs primarily on
      the lips, although it may be located on some other sites on the oral mucosa.
      There are various etiological factors influencing the emergence of
      stomatopyrosis. They are divided into local factors, related to candidiasis,
      dysfunction, problems caused by dentures; systemic factors, with hormonal or
      immunological disturbance, medicines, etc; and, finally, psychogenic factors,
      characterised by various psychological states and conditions like depression,
      anxiety, adaptability and emotional stability. The objective of this research was
      to prove that psychogenic factors cause the burning mouth syndrome sensation.
      Methods which helped us to establish the link between psychogenic factors and the
      emerging of stomatopyrosis were general history of the respondents, clinical
      history, which included both objective and subjective assessment, and
      psychological rating scales and tests. The results have shown that sex of the
      respondents does not make any difference. Diagnosis of the oral disease shows
      that burning is the symptom as well as in the diagnosis of the disease, that
      localisation of the symptom is primarily on lips, followed by tongue, cheeks, and
      palate. The description of the symptoms shows that respondents with
      stomatopyrosis complain of burning and dryness in the mouth cavity. As far as the
      intensity of the symptom is concerned, the results have shown that the symptom is
      in most cases unbearable. The frequency of the occurrence of the symptoms said to
      be continuous. The typical time when the symptom occurs is daytime, followed, by
      night and evening, day and night. Tension dentures and hot food intensify the
      symptom. Subjective change in taste is present in the high percentage. Visual
      analogue scale shows a high degree subjective assessment of the symptoms in the
      mouth cavity. Thermoestesiometry has established that there are no pathological
      changes on the oral mucosa. Psychological rating scales and tests have
      established the presence of psychical changes in a high percentage. What we took
      into account were the most frequent changes: depression, anxiety, adaptability
      and emotional stability. We also established a systematic and a psychiatric
      diagnosis that was necessary for making the right choices when treating people
      with stomatopyrosis. Stomatopyrosis is the state whose factor, apart from local
      and systematic factors, may be psychogenic factor. We think that stymatopyrosis
      may be psychosomatic state that can be cured or treated by appropriate treatment,
      which includes psychiatric treatment as well.

PMID- 10946476
TI  - Diagnostic value of cervical discography in the management of cervical discogenic
      pain.
AB  - We did a retrospective analysis of patients who had a total of 46 cervical discs
      examined by cervical discography and then evaluated the postoperative results of
      14 of the 16 patients who underwent cervical spine fusion at those levels in
      accordance with the results of our discograms. The average symptomatic period
      prior to discography was 12 months, and cervical discogenic pain was successfully
      localized in all 16 patients. Immediately post-cervical discectomy and anterior
      fusion, subjectively, all 14 patients had good to excellent results, and after a
      mean follow-up of 6.5 (1.5 to 14) months, 11 patients (78.6%) continued with good
      to excellent results and three patients (21.4%) developed related pain patterns.
      Thus, cervical discography, in a "select group" of patients with chronic
      intractable neck pain but negative or indeterminate imaging findings who are
      being considered for surgical intervention, can help localize the symptomatic
      level and potentially benefit the patients by surgical intervention.

PMID- 10946477
TI  - Malingering and symptom magnification: a case report illustrating the limitations
      of clinical judgement.
AB  - Malingering and symptom embellishment are of concern to specialists in pain
      medicine. Valid criteria to identify malingering individuals suffering chronic
      pain do not exist. We present a case of a patient on worker's compensation
      identified as a malingerer by six different physicians who had evaluated the
      patient for her chronic complaints. Ultimately, she was found to have a lesion
      that explained all of her subjective complaints. Physicians should exercise
      caution in labeling patients suffering intractable pain as malingerers.

PMID- 10946478
TI  - Physician-assisted suicide in Connecticut: physicians' attitudes and experiences.
AB  - OBJECTIVE: This study examined aspects of physician attitudes toward physician
      assisted suicide (PAS) not fully examined to date: evaluation of risks related to
      PAS, particularly the presence of depression, and the influence of religious and
      professionally-based values. DESIGN: Anonymous, self-administered mailed
      questionnaire using Dillman methodology. PARTICIPANTS: Targeted sample of
      physicians licensed by the Connecticut Department of Public Health in 1997 (n =
      2,805 completed surveys; 40% response rate). DATA INCLUDE: Physician and patient
      characteristics, attitudes toward physician assisted suicide, and confidence in
      treating depression. RESULTS: Religious affiliation, religiosity, ethnicity and
      medical specialty were strongly associated with views on PAS. Seven percent of
      respondents had been asked to write a lethal prescription during the past year,
      15% of whom (n = 24) had complied with at least one request. CONCLUSIONS: Most
      respondents expressed concern regarding certain risks associated with PAS,
      including movement toward involuntary euthanasia and the influence of undetected
      depression. Findings raise practical issues to be addressed through statutory or
      professional safeguards if PAS were to be legalized.

PMID- 10946479
TI  - Long-term stenting for choledocholithiasis.
AB  - Endoscopic biliary sphincterotomy and stone removal has become the standard of
      care for choledocholithiasis. Surgical intervention has been undertaken when
      stones cannot be removed endoscopically. In such patients who are high risk
      surgical candidates, an alternative therapy is the endoscopic placement of long
      term plastic stents to allow biliary decompression. Though such stents usually
      occlude by three months, they may act as a wick to allow drainage of bile into
      the duodenum. This case report describes a patient with choledocholithiasis who
      was treated for 19 months with a biliary stent before expiring from unrelated
      causes.

PMID- 10946481
TI  - Euthanasia, ethics and Socratic dialogue.

PMID- 10946480
TI  - Optimizing the bioavailability of itraconazole.

PMID- 10946482
TI  - Much ado about something. A play in three acts.

PMID- 10946483
TI  - Connecticut has failed its poor, ill patients.

PMID- 10946484
TI  - What is PEPP and what does PEPP mean for health care providers? Payment Error
      Prevention Program.

PMID- 10946485
TI  - Lost heroes, absent mores.

PMID- 10946486
TI  - Oral health in Canada.

PMID- 10946487
TI  - Being sensitive to our environment.

PMID- 10946488
TI  - Halitosis research.

PMID- 10946489
TI  - Cosmetic dentistry: is it really health care?

PMID- 10946490
TI  - Accepting the need for "overkill" in infection control.

PMID- 10946491
TI  - Amalgam.

PMID- 10946492
TI  - Considerations re: fluoride supplementation

PMID- 10946493
TI  - Why CDA must champion Internet connectivity.

PMID- 10946494
TI  - A modified technique for direct, fibre-reinforced, resin-bonded bridges: clinical
      case reports.
AB  - This article presents new modifications to the clinical technique of fabricating
      directly applied resin-bonded fibre-reinforced bridges. Torsional and flexural
      strength is achieved by means of a reinforced polyethylene fibre ribbon
      substructure surrounded by laminated layers of microhybrid and microfilled
      resins. The modifications provide a simple method for creating a better pontic
      ridge relation and improved overall esthetics. Early clinical experience suggests
      that this technique has the potential to give patients a relatively conservative,
      esthetic and periodontally noninvasive alternative for anterior tooth
      replacement.

PMID- 10946495
TI  - Dental caries in Quebec adults aged 35 to 44 years.
AB  - BACKGROUND: The purpose of this study was to assess the prevalence of dental
      caries in Quebec adults aged 35 to 44. METHODS: A stratified sample was used. The
      participation rate was 77% for the questionnaire and 44.5% for the oral
      examination. A total of 2,110 people were examined. The World Health
      Organization's caries criteria were used. Examiner agreement with gold standard
      dentist was excellent at the end of the nine-day training session (Kappa index >
      0.8). RESULTS: The level of caries experience is very high in Quebec adults aged
      35 to 44. Almost half of dental surfaces (65 of 148) have been affected. These
      surfaces are mostly missing (39.3) or filled (23.9). However, there were 1.8
      decayed surfaces in need of treatment per adult, and more than half the people
      (55.5%) had no untreated decayed surfaces. Almost three-quarters of decayed
      surfaces were present in only 14% of the people; lower family income and lower
      education are risk factors. CONCLUSION: Comparison between Quebec and
      industrialized countries (United States, England and the Netherlands) shows that
      in adults 35 to 44, the mean number of decayed teeth is low (between 1.0 and 2.2)
      and the mean number of filled teeth is relatively similar (between 9.6 and 11.1);
      however, Quebec has a higher percentage than the United States of edentulous
      people. As well, in dentate adults, there are 1.6 times more missing teeth among
      Quebecers than among Americans.

PMID- 10946496
TI  - Unconventional dentistry: Part II. Practitioners and patients.
AB  - This is the second in a series of five articles providing a contemporary overview
      and introduction to unconventional dentistry (UD) and its correlation with
      unconventional medicine (UM). Dentists may provide unconventional services and
      use or prescribe unconventional products because of personal beliefs, boredom
      with conventional practice, lack of understanding of the scientific process or
      financial motivation. To promote these UD practices, unrecognized credentials and
      self-proclaimed specialties are advertised. Characteristics of users of
      unconventional practices are varied; however, UD users are more often female and
      highly educated. UD practitioners and users generally appear to be analogous to
      UM practitioners and users. Some UD treatments are more invasive or more costly
      than conventional dentistry.

PMID- 10946497
TI  - Characterization of tachyzoite and bradyzoite antigens of Toxoplasma gondii
      recognized by immunoglobulins G, M and A in an experimental model of reactivated
      toxoplasmosis.
AB  - Toxoplasma gondii tachyzoite and bradyzoite antigens that are recognized during
      reactivated toxoplasmosis were studied in comparison with those recognized during
      acute and chronic infections, in murine models of toxoplasmosis. Both tachyzoite
      and bradyzoite antigens of the RH and KSU T. gondii strains, respectively, were
      resolved by sodium- dodecyl sulphate polyacrylamide gel electrophoresis (SDS
      PAGE) then probed by immunoblot (IB) (Western blot) with mice antisera elicited
      by different states of toxoplasmosis to allow parallel analysis of antigen
      recognition by immunoglobulin G, M, and A antibodies. T. gondii tachyzoite and
      bradyzoite antigens were well studied by IB recording some specific and commonly
      shared antigens. A complex array of T. gondii tachyzoite and bradyzoite antigens
      was revealed in the three states of toxoplasmosis. During reactivated
      toxoplasmosis the commonly shared tachyzoite and bradyzoite antigens were the
      dominantly recorded antigens. Also, antigens of tachyzoite at 48 KDa and
      bradyzoite at 40 KDa were recognized in reactivated toxoplasmosis by IgM and IgG,
      respectively, and not in other states by the same immunoglobulin. The virulent RH
      and avirulent KSU strains of T. gondii showed some similarities.

PMID- 10946498
TI  - Intestinal parasites in relation to haemoglobin level and nutritional status of
      school children in Gaza.
AB  - The prevalence of intestinal parasites and their relations to anaemia and
      nutritional status among school children aged 6-11 years in Gaza was studied. The
      target area is overcrowded with improper sewage disposal system and low
      socioeconomic levels. Anaemia was assessed by haemoglobin level (Hb) and
      nutritional status by anthropometric measurements including weight for age (WA),
      weight for height (WH) and height for age (HA). Intestinal parasites were found
      to be prevalent in Gaza. The overall prevalence was 24.5%. Giardia lamblia
      (62.2%) was the most common parasite detected particularly in age group 6-7
      years, followed by Ascaris Iumbricoides (20.0%), then Entamoeba histolytica
      (18.0%). Parasitosis was generally declining with older age groups for both
      sexes. In general, the prevalence of anaemia was more common in the younger
      children. Malnutrition was found to be prevalent among children. Infected
      children of age group 8-9 years showed higher incidence of low WA than non
      infected ones. The prevalence of stunting and wasting among infected children of
      the youngest group was greater than that observed for controls. Regarding sex, no
      specific trend that relates the prevalence of anaemia with sex. Malnutrition was
      more prevalent among females than males.

PMID- 10946499
TI  - Extended effect of Bacillus thuringiensis H-14 on Culex pipiens adults surviving
      larval treatment.
AB  - Three Bacillus thuringiensis H-14 preparations (a laboratory prepared and two
      commercial formulations namely, Tecknar and Vectobac) were assayed against third
      instar Culex pipiens larvae in order to trace their toxic activity on larval
      treatment. The LC50 values were 0.002, 0.02 and 0.04 ppm. respectively. The
      laboratory strain was tested on the development of Culex pipiens. Larval
      mortality, pupation, adult emergence and sex ratio showed significant differences
      as compared to the non-treated group. Toxic action on the treated larvae with
      laboratory strain of B. thuringiensis H-14 revealed drastic effect on larval mid
      gut epithelium and resulted in extended pathological activity in adults, which
      survived larval treatments. Nervous and reproductive systems were found to be the
      most damaged systems in female adults.

PMID- 10946500
TI  - Isolation and structural characterization of Toxocara vitulorum specific antigen
      and its potency in diagnosis of toxocariasis among buffalo calves.
AB  - A method of affinity chromatography purification of species-specific antigen from
      Toxocara vitulorum adult worm is described. The purification process resulted in
      a fraction with 9315 fold increase in specific activity compared to crude
      extract. Structural characterization of the isolated fraction by SDS
      polyacrylamide gel electrophoresis, isoelectric focusing and amino acid analysis
      showed that the fraction consists of only two polypeptides of 92 kD and 87 kD
      with isoelectric points of 8.8 and 8.9. Moreover, 17 amino acids were identified
      in the fraction with high proportions of only three of them (tyrosine, glycine
      and glutamic). The isolated antigen proved potency in the diagnosis of
      toxocariasis among buffalo claves using ELISA which recorded 100% sensitivity.

PMID- 10946501
TI  - Soluble adhesion molecules as a marker of disease severity in human fascioliasis.
AB  - Fasciola gigantica is one of the parasites which affect the liver by producing
      biliary tract lumen syndrome. Soluble adhesion molecules namely soluble
      intercellular adhesion molecule-1 (sICAM-1) and soluble E-selection (sELAM-1)
      were assayed in human fascioliasis cases with or without complications. It was
      found that sICAM-1 and sELAM-1 were significantly increases in complicated cases
      more than the control group, while only sICAM-1 was significantly increased in
      complicated cases more than non complicated ones. However, non of both soluble
      adhesion molecules were significantly elevated in non complicated cases as
      compared to controls suggesting that sICAM-1 is a useful marker for
      differentiation between complicated and non complicated cases of human
      fascioliasis.

PMID- 10946502
TI  - Indirect haemagglutination (IHA) for the diagnosis of hydatid disease in Yemen.
AB  - Antihydatid cyst antibodies from sera of infected Yemeni patients were detected
      using indirect haemagglutination assay (IHA). Antihydatid cyst antibodies were
      detected in 34 out of 38 serum samples (89% sensitivity). The specificity of the
      assay was defined to be 97.0% as cross reactivity only noticed with serum from
      one patient with Schistosoma mansoni out of 11 Schistosoma positive patients
      examined. Results were discussed.

PMID- 10946503
TI  - Studies on heterologous resistance between schistosomiasis mansoni and
      fascioliasis.
AB  - S. mansoni and F. gigantica GSTs were purified from adult worm homogenates by
      affinity chromatography. Assessment of both SmGST and FgGST as candidate vaccines
      was done by comparing vaccinated mice groups challenged with S. mansoni cercariae
      with control ones in terms of worm load, tissue egg number viability and
      maturity, and the survival rate of the animals. SmGST 5 ug vaccination generally
      appeared to confer best protection against homologous challenge followed by FgGST
      5 ug while vaccination with both antigens using low doses (2 ug) appeared to have
      no specific role in decreasing worm load but had significant effects on egg
      production.

PMID- 10946504
TI  - Sheep-dog-man. The risk zoonotic cycle in hydatidosis.
AB  - Hydatid cyst, the larval cestod of Echinococcus granulosus infects both man and
      animal. In the last five years, fourteen cases have been surgically treated in
      the Universities Hospitals of Cairo (9) and Ain Shams (5). The highly infected
      site was the liver and the least was the spleen. On the other hand, a total of
      2,871,510 sheep slaughtered in the governmental abattoirs over five years (1995
      1999) showed an overall hydatidosis of 0.33%. The highly infected site was the
      lung followed by the liver. Cystic infection in other sites rarely occurred.
      Generally speaking, hydatidosis is not a so dangerous public health problem in
      Egypt. However, sheep play the important role in dissemination of the disease.
      This is due to the fact that their cysts are the highly fertile ones as compared
      to other animal intermediate hosts. So, the risk cycle in hydatidosis is sheep
      dog-man.

PMID- 10946505
TI  - Metacyclogenesis of Leishmania major in an acidic medium.
AB  - An acidic medium was used to stimulate the production of a homogeneous stationary
      phase promastigotes, morphologically and functionally similar to the in vivo
      infective form. They possessed a short (< 8 Um) and narrow (< 1.5 Um.) cell body
      with a flagellum twice or more its length. They were PNA, highly infective to
      peritoneal macrophages in vitro and expressed high phosphatase activity. By
      elevating the incubating temperature, almost all of these promastigotes were
      transformed to amastigotes.

PMID- 10946506
TI  - Evaluation of different means of control of snail intermediate host of
      Schistosoma mansoni.
AB  - Four water courses having the same conditions and snail density were chosen for
      this study. All methods were applied simultaneously in April. Snails were
      collected monthly to evaluate the malacological effect. A single application of
      100 ppm dried A. maritima decreased the snail density significantly within one
      month. Snail density was maintained very low until the end of the year. Fresh
      Azolla pinnata applied in a dose of 280 ppm lowered snail density to a level
      intermediate between Ambrosia maritima and Bayluscide. Snail population began to
      build 5 months later. Bayluscide applied once at a dose of 1 ppm lowered
      significantly the snail density. This lowering was maintained for 4 months after
      which snails began to build up and remained high until the end of the study
      period. Clearing of vegetations was followed by abrupt lowering of snail density
      which was maintained for a period longer than that following Bayluscide and
      Azolla.

PMID- 10946507
TI  - Camel: a new Egyptian host for Fasciola gigantica.
AB  - F. gigantica is a known liver fluke in Egypt. Infection has been reported in
      sheep, goats, buffaloes, cows and donkeys. Human cases have been reported from
      several governorates. This paper records camels as an additional host for F.
      gigantica in Egypt. In such materials worms attained a length of 6.0-6.3 cm.

PMID- 10946508
TI  - Effect of carnosine administration on certain metabolic parameters in bilharzial
      infected hamsters.
AB  - This study was designed to test the ability of carnosine to cure the metabolic
      disturbances induced by Schistosoma mansoni parasite. Results indicate that
      parasitic infection caused elevation of liver weight/body weight of S. mansoni
      infected hamsters, induced lipid peroxidation and reduced glycogen level.
      Moreover, the adenylate energy charge (AEC), ATP/ADP and ATP/AMP concentration
      ratios were markedly lower in infected hamsters. Administration of carnosine (10
      mg/day) for 15 days either concurrent with infection, 2 and 4 weeks post exposure
      was effective in reducing worm burden and egg count only when given at the time
      of infection. It was also effective in renormalizing most of the measured
      parameters confirming the glycogen repletion, the antioxidant and AEC correcting
      actions of carnosine.

PMID- 10946509
TI  - The impact of environmental and entomological factors on intervillage filarial
      focality in the Nile Delta.
AB  - In the Nile Delta of Egypt, levels of W. bancrofti infection in humans vary among
      nearby villages. Ecological and entomological factors that might explain
      variability between adjacent villages, El Qolzom (QOL) and Kafr Shorafa (KSH)
      with respective 10.8% and 2.1% microfilaria (MF) prevalence were examined. The
      epidemiological study covered 127 and 79 houses scattered in QOL and KSH,
      respectively, and described 25 items relating to housing characters, socio
      economic state and human activities. It revealed that QOL is more rural than KSH,
      and therefore would be more favorable to the vector mosquito population and
      hence, filarial parasite transmission in QOL. Weekly records (N = 81 and 62 for
      QOL and KSH, respectively) of ambient temperature, relative humidity and wind
      speed taken at sunset, over 3 months during summer, revealed no significant
      variation between villages. Those measured at sunrise revealed significant,
      although inconsistent, differences at a particular month, but no difference over
      the whole period. Whether climatological conditions could have influenced
      mosquito bionomics in the study villages is questionable. Abundance of female Cx.
      pipiens collected weekly by standard sampling methods using 247 and 240 dry ice
      baited CDC trap-nights in QOL and KSH, respectively, oral aspiration from within
      346 and 304 respective house-nights, and 65 and 40 respective ovitrap-nights, did
      not vary significantly over the whole study period. Daily survival and survival
      to infectivity rates of wild-caught mosquitoes were based on parity and were
      generally more elevated in QOL than KSH. Monthly records of abundance and
      survival seemed to favor filaria transmission by mosquitoes in QOL. Autogeny
      amounted to 6.5 and 20% for QOL and KSH, respectively. Experimental infection of
      Cx. pipiens from the study villages with W. bancrofti revealed that QOL females
      were 3.3 times more efficient vectors than KSH ones, mainly because QOL
      mosquitoes survived longer. The ultimate outcome of observed entomological
      factors might explain its preponderance in QOL.

PMID- 10946510
TI  - Assessment of the diagnostic system of Schistosoma infection at rural health unit
      level, Egypt.
AB  - The study sample was 6 rural health units and 405 attendants. Assessment of
      inputs was done through review of documents, charts, interviews, questionnaires
      and direct observation. Assessment of accuracy of the techniques was done by
      cross matching the results of urine and stools examination using different
      techniques (filtration and sedimentation for urine, and Kato-Katz and direct
      smear for stools). Results of technicians were compared with that of
      investigators using the same technique. Two days examinations of urine and stools
      samples were done by investigators using nucleopore and Kato-Katz, respectively.
      Environment assessment showed that, political and economic environments were the
      most influencing components that affect the system of diagnosis. Organization
      assessment showed that organization structure adapted to a large extent its
      objectives. However, decentralization and technological development were
      required. Filtration was more sensitive than sedimentation (82% and 51.3%,
      respectively). Specificity and PV+ were 100% for both tests. While, PV- and
      efficiency were 97.6% and 97.8% for filtration, and 93.7% and 94.1% for
      sedimentation, respectively. Sensitivity of Kato-Katz was higher than direct
      smear (88.5% and 11.5%, respectively). Kappa coefficient ranged between 0.63 and
      1 as regards results of technicians compared to that of investigators. Mean daily
      workload of urinary examinations per technician ranged between 5.8 and 34.8. That
      of stools examinations was 5.3 and 32.4. Satisfaction rates ranged between 51.3%
      and 100% for different rural health units. Strengths and opportunities should be
      intensified. Weaknesses and threats should be treated.

PMID- 10946511
TI  - Anti-fasciola IgG isotypes among patients with fascioliasis before and after
      treatment.
AB  - Stool examination using modified Kato thick smear method was performed to detect
      Fasciola eggs and other parasites. Abdominal pain was the major presenting
      symptom (83.3%) followed by pallor (71.6%) and fever (16.7%). Anaemia and
      hepatomegaly were recorded in 70% of patients compared to 25% with splenomegaly.
      Abdominal ultrasonography revealed hepatomegaly and common bile duct dilatation
      in 70% of patients. Moreover, 6 cases showed Olympic game rings which is
      diagnostic. All of patients had positive IgG4 levels, 58 cases were found
      positive for specific total IgG and IgG1, whereas, only 36 cases had positive
      IgG2 levels (60%). All negative control group showed no cross reactions. On the
      other hand, ELISA detecting IgG4 showed the highest specificity (95%), followed
      by IgG2 (85%) and the least specific test was obtained with detection of IgG
      (70%) and IgG1 (65%). One week after treatment, 90% of patients were completely
      cured. One and 3 months after treatment, the cure rate was 83.3%. In completely
      cured patients, none of anti-Fasciola isotypes was significantly changed.

PMID- 10946512
TI  - A KAP study among staff and student nurses about infection control in Theodor
      Bilharz Hospital.
AB  - The aim of this study is to assess the knowledge, attitude and practice of staff
      and student nurses in Theodor Bilharz Research Institute Hospital towards simple
      protective measures such as: hand washing practices, recapping of syringe needles
      after use, and their awareness of Hepatitis B and C viruses prevention and
      control. A questionnaire is designed and distributed to all student nurses in the
      school (41 students out of 45), and to all staff nurses working in the hospital
      (39 nurses out of 50), with a total of 80 out of 95. Scoring system is used for
      data analysis. The overall scoring of KAP for the three items studied are below
      80%, which means that they really need health education about these items. Thus,
      it is very important to create public awareness in the hospital community, and
      among nurses about the concept of infection control. This will be done through
      formal and informal instructions, by organizing regular courses and posters. It
      is very essential to provide safe disposal of syringe needles in special
      containers, have facilities for hand washing during work and apply HB vaccine for
      nurses working in the hospital. Meanwhile, a highly motivated behavior should be
      enabled and reinforced through realization of the regulatory and organizational
      factors for better implementation arrangement, which all supplement the
      educational intervention directed to change rather than just planning.

PMID- 10946513
TI  - Diagnosis of toxoplasmosis in children with malignancy.
AB  - The study aimed at the diagnosis of toxoplasmosis in 73 children with malignancy;
      31 with lymphoma (22 with Hodgkin's and 9 with non-Hodgkin's lymphoma) and 42
      with leukemia (34 with acute lymphoblastic leukemia and 8 with acute myelogenic
      leukemia). In positive cases toxoplasmosis was manifested by any of the
      following; fever, lymph node enlargement, neurological manifestations and/or
      hepatosplenomegaly. The indirect hemagglutination test (IHA) for toxoplasmosis
      detected 4 (5.4%) positive cases with malignancy, 2 with Hodgkin's lymphoma, one
      with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia. The
      immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) detected only one
      (1.4%) case with Hodgkin's lymphoma. Immunoglobulin G (IgG) ELISA detected 6
      (8.2%) positive cases, 3 with Hodgkin's lymphoma, one with non-Hodgkin's lymphoma
      and 2 cases with acute lymphoblastic leukemia. Polymerase chain reaction for
      detection of parasite DNA in blood (PCR) was the most useful in diagnosing
      toxoplasmosis with malignancy, as it was able to detect 9 (12.3%) positive cases;
      5 (6.8%) with Hodgkin's lymphoma, one (1.4%) with non-Hodgkin's lymphoma and 3
      (4.1%) with acute lymphoblastic leukemia. No positive toxoplasmosis cases were
      detected with acute myelogenic leukemia by any of the above methods.

PMID- 10946514
TI  - Assessment of the role of soluble intracellular adhesion molecule-1 (sICAM-1) in
      the pathogenesis and as a marker of disease severity in different stages of human
      schistosomiasis and toxoplasmosis.
AB  - The role of soluble intracellular adhesion molecule 1 (sICAM-1) in the
      pathogenesis and its relevance to disease severity was assessed in different
      stages of human infection with S. mansoni, S. haematobium and T. gondii. The
      levels of sICAM-1, obtained in the current study correlated with disease
      severity, degree of cell destruction and type of immune response. Highest sICAM-1
      levels were observed in only two groups (hepatosplenic schistosomiasis and
      patients with mixed active S. haematobium and T. gondii infections), while in the
      other two groups (separate cases of active S. haematobium infection or latent T.
      gondii infection) showed no significant rise in sICAM-1 levels.

PMID- 10946515
TI  - Susceptibility of Biomphalaria alexandrina to infection with Schistosoma mansoni:
      correlation with the activity of certain glycolytic enzymes.
AB  - The importance of the glycolytic flux for the success of Biomphalaria-Schistosome
      sporocyst interaction was acertained in this study. Hexokinase (HK), pyruvate
      kinase(PK), glucose phosphate isomerase(GPI) and lactate dehydrogenase (LD) as
      four important glycolytic enzymes were markedly stimulated in trematode infected
      Biomphalaria alexandrina when measured two weeks post exposure to infection with
      Schistosoma mansoni miracidia. On the other hand phosphoenolpyruvate carboxy
      kinase (PEPCK), glucose-6-phosphatase (G6Pase) and fructose 1,6
      diphosphatase(FDPase) as three gluconeogenic enzymes were slightly affected which
      confirm the importance of the glycolytic pathway for schistosome-exposed snails.
      Effect of LC25 of Solanum nigrum leaves dry powder as plant molluscicide on HK,
      PK and GPI were tested. Treatment with this plant resulted in a significant
      inhibition of these three investigated enzymes. LC10 concentrations of S. nigrum
      reduced considerably the infection rate of B. alexandrina with S. mansoni to be
      34% compared to an infection rate of 80% in control, non-treated snails. Longer
      prepatent period and remarkable decrease in cercarial production was also
      recorded in snails treated with the sublethal concentrations of the molluscicide.
      As conclusion, susceptibility of B. alexandrina to infection with the digenetic
      trematode S. mansoni is correlated to the activity levels of the glycolytic
      enzymes. Moreover, sublethal and less pollutant concentration of S. nigrum could
      be recommended to control schistosomiasis by disturbing the intramolluscan
      environment of the parasite.

PMID- 10946516
TI  - Molecular identity of major cross-reactive adult antigens in Fasciola gigantica,
      Toxocara vitulorum and Moniezia expansa.
AB  - Cross reactivity between Fasciola gigantica, Toxocara vitulorum and Moniezia
      expansa whole worm extracts was proved by ELISA. Intense cross-reaction was
      observed between F. gigantica and M. expansa rather than between each of them and
      T. vitulorum. As judged by immunoblot, the cross-reactive antigens in F.
      gigantica which recognized by T. vitulorum antisera was 109 kD while this
      component in addition to another one of 52 kD were detected by M. expansa sera in
      the same extract. Furthermore, T. vitulorum antigen which cross-reacted with F.
      gigantica was 133 kD and with M. expansa was 143 kD. Antigens responsible for
      cross-reactivity in M. expansa were 130 kD and 210 kD to T. vitulorum and F.
      gigantica respectively.

PMID- 10946517
TI  - Bacillus thuringiensis var. israelensis (B.t. serotype H-14) against Lucilia
      sericata third stage larvae.
AB  - Bacillus thuringiensis var. israelensis (B.t. H-14) was mixed with minced liver
      in different concentrations and given to newly moulted third stage larvae of
      Lucilia sericata. The LC50 was 9 ppm (0.76-1.5) and the slope function was 0.59.
      This bacterium which is safe and friendly proved to be effective against the
      myiasis producing L. sericata larvae.

PMID- 10946518
TI  - Structural characterization and immunolocalization of egg antigens cross-react
      with Toxocara vitulorum, Fasciola gigantica and Moniezia expansa mature flukes.
AB  - A structural homology between eggs of Toxocara vitulorum, Fasciola gigantica and
      Moniezia expansa was proved by the use of SDS-PAGE. In immunoblot, 9, 11 and 7
      polypeptides were recognized in F. gigantica, M. expansa and T. vitulorum eggs
      respectively by their respective rabbit anti-adult antisera. Moreover, components
      of 240 KD and 206 KD were recognized in the three eggs by different anti-adult
      antisera. The anatomic localization of the crossreactive epitopes in eggs was
      determined by indirect immunofluorescence microscopy. The cross-reactive epitopes
      were mainly associated with embryonted cells of F. gigantica, egg shell, larvae
      and vitelline membranes of T. vitulorum and egg shall and granular layer of M.
      expansa.

PMID- 10946519
TI  - Hypothalamic origin of reproductive failure in chronic experimental
      toxoplasmosis.
AB  - Laboratory bred female mice were used to study the effect of chronic
      toxoplasmosis on reproductive performance. The animals were infected with small
      dose (3 x 10(3)) tachyzoites of Toxoplasma parasites. The female mice were mixed
      with normal males for one week, then separated to monitor their reproductive
      performance one and two months post infection (p.i). Mice bred one month p.i.
      showed reproductive failure with one of twenty females delivered two sick
      newborns. The others did not complete pregnancy and faetal wastage occurred. Mice
      bred two months p.i. were infertile. Histopathological examination of the ovaries
      revealed impaired folliculogenesis and atropic degeneration. Coronal sections of
      cerebrum showed widespread vasculitis, focal disruption of the ependymal cells
      lining both the lateral and third ventricles. The supraoptic and paraventricular
      hypothalamic nuclei were deformed and showed pyknotic neurons. Immunoperoxidase
      staining was used to detect IgG and IgM deposits in brain tissue. IgG deposits
      were found on the vicinity of Toxoplasma cysts and focally in the paraventricular
      zone. So, the reproductive failure of infected mice was due to hypogonadotrophic
      hypogonadism secondary to hypothalamic dysfunction as a result of chronic
      toxoplasmosis.

PMID- 10946520
TI  - Anisakis and fish induced urticaria.
AB  - Skin tests using prepared Anisakis antigen and commercially available fish
      antigen were done. Also, specific IgE detection for Anisakis was done by RAST
      method. Two patients out of 20 showed positive skin test and positive RAST to
      larval Anisakis antigen, and negative skin test to fish antigen. These 2 patients
      were considered hypersensitive to Anisakis.

PMID- 10946521
TI  - Seasonal abundance of Ornithodoros (O.) savignyi and prevalence of infection with
      Borrelia spirochetes in Egypt.
AB  - The seasonal dynamics of Ornithodoros (O.) savignyi and infection with Borrelia
      sp. in the tick, domestic animals and man were investigated in the village of
      Dahshore, Giza governorate from August 1996 through July 1997. The tick
      population densities of adults and immatures were high during the period from
      June to October with maximum levels in August and September respectively. Adults
      predominated (58.6%-80.0%) in October to May with the highest abundance in
      January while immatures prevailed (51.3%-65.8%) during the rest of the year
      reaching a peak in September. Of 1202 tick examined, the spirochetes were
      detected in 427 (35.5%). The annual infection rate in adults and immatures varied
      from 34.4%-36.9% with no significant difference among larvae, nymphs, males and
      females. Of 1396 sera from man and 553 sera from host animals tested, 309 (22.1%)
      and 157 (28.4%), respectively, were reactive for antibody to Borrelia sp. antigen
      with the highest infection rate in camel (47.8%), followed by sheep (23.8%), goat
      (18.0%) and cow (16.0%), then the least in buffalo (10.9%). Changes in prevalence
      of Borrelia infection in the tick population correlated positively with changes
      in antibody prevalence in man and camel and with changes in the tick population
      density. The four events were lowest in winter and early spring and increased
      afterward to reach maxima during summer or the early fall (July-September).

PMID- 10946522
TI  - Diagnosis of early pre-patent schistosomiasis by cystatin capture enzyme-linked
      immunosorbent assay.
AB  - To test the efficacy of detecting anti-Schistosoma mansoni cysteine proteinase
      antibodies (CP Abs) by cystatin capture (CC) ELISA in the diagnosis of prepatent
      schistosomiasis (before egg passing); 253 schistosome negative individuals were
      selected and divided into two groups. The first comprised 118 children whose
      first water contact occurred in March and April 1999 (primarily infected), and
      the second 135 individuals were previously treated for schistosomasis (re
      infected). All the individuals were followed up triweekly by stool for detecting
      schistosome eggs and by serological tests for detecting antibodies against CP and
      anti-soluble egg antigens (SEA) by ELISA technique. CP seropositivity was
      detected in 92 from all examined individuals, out of them 38 were primarily
      infected (PI) children (20 of them were pre-patently treated), the rest; 54 were
      re-infected patients (28 out of them were pre-patently treated). The untreated
      (44) individuals from both groups were followed up till they passed eggs within 4
      weeks and then were treated (post-patent). CP Abs were reassessed for the 92
      patients after treatment, only 11 (12%) were still seropositive with marked
      decrease in optical density (O.D.) level than before treatment. Anti-SEA IgM Abs
      were sought in the 92 CP seropositive sera, and the seropositivity rate was lower
      in 38 PI children (5.3%) than in the 54 re-infected individuals (92.6%). The anti
      SEA seropositivity rate in the PI children was 5% in the pre-patent and was 94.4%
      in the post-patent. None of the 161 CP seronegative individuals passed eggs up to
      12 weeks.

PMID- 10946523
TI  - Assessment of two natural marine toxins (Microcystis aeruginosa and Parasicyonis
      actinostoloides) for the control of some medical and agriculture insects with
      reference to the action on mice.
AB  - The present work describes the insecticidal potentiality from Microcystis
      aeruginosa (cyanobacteria) and Parasicyonis actinostoloides (Sea anemone) water
      extracts against 3rd larval instar of medical insects (Musca domestica and Culex
      pipiens) and 4th larval instar of agriculture insects (Spodoptera littoralis and
      Agrotis ipsilon. The LD50s of M. aeruginosa extract were 1.94, 2.33, 7.59 and
      9.10 mg/ml. for M. domestica, C. pipiens, S. littoralis and A. ipsilon).
      respectively. While LD50s of P. actinostoloides extract were 19.28, 24.7, 27.3
      and (29.4) mg/ml. for M. domestica, C. pipiens, S. littoralis, and A. ipsilon
      respectively. The aqueous extracts of M. aeruginosa and P. actinostoloides had no
      acute or chronic marked effect on mice as serum acetyl cholinesterase and gave
      more or less nearly the same level of AchE activity at the end of decapitation
      periods.

PMID- 10946524
TI  - Partial characterization of acidic proteinase in the midgut of Parasarcophaga
      surcoufi larvae (Diptera: Sarcophagidae).
AB  - Activity of acidic proteinase in the midgut of larval Parasarcophaga surcoufi was
      investigated and partially characterized. Larval midgut extract showed a moderate
      acidic pH (pH 4) optimum for hydrolysis of haemoglobin. The proteolytic activity
      of the larval midgut was estimated by hydrolysis of haemoglobin, and was found to
      be inhibited by pepstatin (aspartic proteinase inhibitor), dithiothreitol (DTT)
      and mercaptoethanol; while it was not inhibited by the soybean trypsin inhibitor
      (STI) and EDTA. These characteristics may imply that cathepsin D-like proteinase
      is an effective acidic proteinase present in the Parasarcophaga surcoufi larval
      midgut.

PMID- 10946525
TI  - HIV/AIDS: a global epidemic.

PMID- 10946526
TI  - Eliminating racial and ethnic disparities in health: the role of the ten leading
      health indicators.

PMID- 10946527
TI  - Efficacy and safety of cerivastatin and pravastatin in the treatment of primary
      hypercholesterolemia.
AB  - In this randomized, double-blind, parallel group study, the efficacy and safety
      of cerivastatin (0.3 mg) and pravastatin (20 mg) were compared in 402 patients
      with primary hypercholesterolemia with and without documented coronary heart
      disease or peripheral vascular disease. After 8 weeks of treatment, cerivastatin
      provided significantly greater reductions than pravastatin in low-density
      lipoprotein (LDL)-cholesterol (31.1% vs. 26.0%; p < 0.0001) and total cholesterol
      (21.1% vs. 17.8%; p < 0.0001). A greater proportion of patients treated with
      cerivastatin than pravastatin achieved > 30% and > 40% reductions from baseline
      in LDL-cholesterol. Both agents also increased high density lipoprotein
      cholesterol and reduced triglycerides. Overall, 65.1% of patients treated with
      cerivastatin and 63.3% of patients with pravastatin achieved LDL-cholesterol
      goals defined by the National Cholesterol Education Program. Both drugs were well
      tolerated, with most adverse events being mild. These results demonstrate that
      cerivastatin (0.3 mg) is a highly effective 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor, which enables a large proportion of patients to achieve
      clinically meaningful reductions in LDL-cholesterol.

PMID- 10946528
TI  - The paradox of coronary heart disease in African-American women.
AB  - Coronary heart disease is the leading cause of death in the United States in both
      men and women. Much has been written on the ill effects of this disease in the
      general population; however, its ramifications in African-American women have
      been overlooked. Without a doubt, this group has a higher mortality and morbidity
      than African-American men and white women below the age of 55. Despite the lower
      angiographic prevalence of disease, when symptomatic coronary heart disease
      develops, the outlook is dismal. Today's research must concentrate on the
      ramifications of coronary heart disease in this population to improve the health
      standard of the general populace.

PMID- 10946530
TI  - An assessment of home remedy use by African Americans.
AB  - This analysis represents the first national look at family and individual use of
      home remedies by African Americans. The purpose is to examine home remedy usage
      by African-American individuals and their families and assess the relationship
      between sociodemographic characteristics and home remedy usage for African
      American families and African-American individuals. Using logistic regression, a
      secondary analysis of the National Survey on Black Americans (NSBA) data (N =
      2107) was conducted to examine factors associated with home remedy use.
      Multivariate analysis indicated that parent's education, importance of religion,
      living with a grandparent, and living in a rural area were associated with
      families' use of home remedies. Age, gender, living with a grandparent,
      education, and geographic region were associated with individual home remedy use.
      The results of this research may provide insight to health care practitioners in
      their challenge of appropriately integrating self-care practices (i.e., home
      remedy use) and the use of the formal health care system among the patients that
      utilize both "scientific" and "folk" medical systems. When possible, treatment
      plans should be adapted to consider patients' demographics, health beliefs, and
      self-care practices. Health care providers should encourage patient and family
      involvement and dialogue regarding therapeutic approaches. As more information
      becomes available, health care practitioners will be better able to ascertain the
      possible health consequences of concurrent usage of home remedies and
      prescription drug therapies.

PMID- 10946529
TI  - Folate and vitamin B12 status of adolescent girls in northern Nigeria.
AB  - The diets of populations in many developing countries are low in folate and
      vitamin B12 and a deficiency of either of these vitamins results in increased
      risk for cardiovascular disease and neural tube defects. The rates of neural tube
      defects in Nigeria are among the highest reported worldwide. Since many girls
      marry at an early age in northern Nigeria, we therefore determined the folate and
      vitamin B12 status of adolescent girls between 12 and 16 years of age in
      Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/-
      5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations
      lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the
      subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower
      limit of the reference range for their age group. Serum homocysteine was measured
      in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The
      majority of subjects had serum homocysteine concentrations above the upper limit
      of the reference range for their age group. We conclude that the adolescent girls
      we studied were at greater risk for vitamin B12 deficiency than folate
      deficiency. This conclusion is consistent with the fact that their diet included
      few foods that contained vitamin B12.

PMID- 10946531
TI  - Can self-reported behavioral factors predict incident sexually transmitted
      diseases in high-risk African-American men?
AB  - The known link between sexually transmitted diseases (STD) and human
      immunodeficiency virus (HIV), coupled with the increasing prevalence of HIV in
      African-American men, makes understanding STD transmission trends in this group
      important for directing future preventive measures. The goal of this study was to
      determine if self-reported behavioral factors are predictive of incident sexually
      transmitted diseases in a group of high risk, HIV-negative African-American men.
      Five hundred and sixty-two "high risk" (defined as having four or more partners
      in the last year or having been diagnosed with an STD in the last year) HIV
      negative African-American men were administered a baseline behavioral survey and
      followed to detect an incident STD. Overall, 19% (n = 108) of the patients
      acquired an incident STD during the study period. In multivariate Cox
      proportional hazards analysis, the only factor associated with an incident STD
      was age < or = 19 (hazard ratio, 2.16; 95% confidence interval, 1.03 to 4.54). No
      other risk factors were statistically significant. In conclusion, self-reported
      behavioral factors, such as substance use and sexual practices, do not seem to be
      a good measure of STD risk among a group of high risk, HIV-negative, African
      American men.

PMID- 10946532
TI  - Helicobacter pylori infection in sickle cell disease.
AB  - Abdominal pain is a common presenting symptom in adults with sickle cell disease
      (SCD). One case of Helicobacter pylori gastritis has been reported in a child
      with sickle cell anemia. H. pylori-induced peptic ulcer disease (PUD) has not
      previously been reported in adults with SCD. We report eight cases of H. pylori
      infection in adult sickle cell patients presenting with acute or recurrent
      abdominal pain and/or gastrointestinal bleeding. In all cases, H. pylori serology
      (IgG) was positive, and three patients had gastric or duodenal ulcer by
      endoscopic examination. All patients responded to H. pylori treatment with
      complete resolution of symptoms by 4 weeks. The prevalence of H. pylori infection
      in SCD is unknown, but patients may be at increased risk for H. pylori-induced
      PUD and complications due to pre-existing anemia, increased nonsteroidal anti
      inflammatory drug use, and alloimmunization which may delay necessary
      transfusion. It is important that the differential diagnosis of abdominal pain in
      adults with SCD include nonsickle cell-related disorders such as PUD. When
      confirmed, a definitive etiology of PUD must be determined so that appropriate
      treatment strategies can be initiated promptly and excess morbidity avoided.

PMID- 10946533
TI  - The influence of distinctive processing on retrieval-induced forgetting.
AB  - Recall of a portion of a previously experienced list benefits subsequent recall
      of that portion of the list but leads to poorer recall of nonpracticed items from
      the same set (Anderson, Bjork, & Bjork, 1994). One explanation for this retrieval
      induced forgetting is that during practice of part of a set, the non-practiced
      items compete for recall and are suppressed; this suppression process inhibits
      later recall of the nonpracticed items. Two experiments were conducted to
      investigate the relationship between distinctive processing of the original set
      and retrieval-induced forgetting, on the assumption that distinctive processing
      reduces response competition. In the first experiment, distinctive processing
      induced by difference judgments among the studied items did reduce forgetting
      relative to a standard encoding task and a similarity judgment task. In fact, the
      difference judgment task completely eliminated retrieval-induced forgetting. In
      the second experiment, the similarity judgment task was analyzed in relation to a
      task assumed to foster associative integration (Anderson & McCulloch, 1999). Even
      though the similarity judgment met the requirements for associative integration,
      retrieval-induced forgetting persisted following similarity judgment. The results
      are consistent with the view that distinctive processing benefits memory within
      an organizational context (Hunt & McDaniel, 1993; Smith & Hunt, in press).

PMID- 10946534
TI  - What is this thing called frequency?
AB  - When researchers are interested in the influence of long-term knowledge on
      performance, printed word frequency is typically the variable of choice. Despite
      this preference, we know little about what frequency norms measure. They
      ostensibly index how often and how recently words are experienced, but words
      appear in context, so frequency potentially reflects an influence of connections
      with other words. This paper presents the results of a large free association
      study as well as the results of experiments designed to evaluate the hypothesis
      that common words have stronger connections to other words. The norms indicate
      that common words tend to be more concrete but they do not appear to have more
      associates, stronger associates, or more connections among their associates. Two
      extralist cued recall experiments showed that, with other attributes being equal,
      high- and low-frequency words were equally effective as test cues. These results
      suggest that frequency does not achieve its effects because of stronger or
      greater numbers of connections to other words, as implied in SAM. Other results
      indicated that common words have more connections from other words, including
      their associates, and that free association provides a valid index of associative
      strength.

PMID- 10946535
TI  - Retrieval latency and "at-risk" memories.
AB  - Does retrieval latency reflect variations in the strength of associations in
      episodic memory? In three experiments, subjects were given a single study and
      test trial on each of five lists of 10 paired associates. Spoken recall latencies
      were measured. When the subjects were later given a second test, initial recall
      latency was systematically related to intertest retention--that is, the faster
      the initial correct recall of a pair, the more likely a pair was to be recalled
      at the second test. This effect occurred at retention intervals of 5 min, 30 min,
      and 24 h and was present in the data for individual subjects. The results are
      consistent with the classical view of latency as a measure of trace strength and
      stand in sharp contrast with results reported by Benjamin, Bjork, and Schwartz
      (1998) that showed that fast retrievals from semantic memory were more poorly
      retained than slower ones.

PMID- 10946536
TI  - Modality differences in short-term memory for rhythms.
AB  - Prior research has established that performance in short-term memory tasks using
      auditory rhythmic stimuli is frequently superior to that in tasks using visual
      stimuli. In five experiments, the reasons for this were explored further. In a
      same-different task, pairs of brief rhythms were presented in which each rhythm
      was visual or auditory, resulting in two same-modality conditions and two cross
      modality conditions. Three different rates of presentation were used. The results
      supported the temporal advantage of the auditory modality in short-term memory,
      which was quite robust at the quickest presentation rates. This advantage tended
      to decay as the presentation rate was slowed down, consistent with the view that,
      with time, the temporal patterns were being recoded into a more generic form.

PMID- 10946537
TI  - Perceptual interference at encoding enhances item-specific encoding and disrupts
      relational encoding: evidence from multiple recall tests.
AB  - Interfering with perception during encoding can enhance later memory, a
      phenomenon known as the perceptual interference effect. This effect is
      investigated in the context of the item-specific-relational framework (e.g., Hunt
      & McDaniel, 1993), which suggests that the perceptual interference enhances item
      specific encoding and impedes relational encoding. Two experiments performed with
      multiple recall tests support this view. Prior research indicates that item
      specific processing increases item gains across tests, whereas relational
      processing protects against item losses (e.g., Burns, 1993; Klein, Loftus,
      Kihlstrom, & Aseron, 1989). Consistent with the item-specific-relational
      framework, perceptual interference produced significant increases in both item
      gains and losses relative to a control condition.

PMID- 10946538
TI  - Expectancies generated by recent exposure to melodic sequences.
AB  - In four experiments, we examined the effects of exposure to unfamiliar tone
      sequences on melodic expectancy and memory. In Experiment 1, 30 unfamiliar tone
      sequences (target sequences) were presented to listeners three times each in
      random order (exposure phase), and listeners recorded the number of notes in each
      sequence. Listeners were then presented target and novel sequences and rated how
      well the final note continued the pattern of notes that preceded it. Novel
      sequences were identical to target sequences, except for the final note. Ratings
      were significantly higher for target sequences than for novel sequences,
      illustrating the influence of exposure on melodic expectancy. Experiment 2
      confirmed that without exposure to target sequences, ratings were equivalent for
      target and novel sequences. In Experiment 3, new listeners were assessed for
      explicit memory for target sequences following the exposure phase. Recognition of
      target sequences was above chance, but unrelated to expectancy judgments in
      Experiment 1. Experiment 4 replicated the exposure effect, using a modified
      experiment design, and confirmed that the effect is not dependent on explicit
      memory for sequences. We discuss the idea that melodic expectancies are
      influenced by implicit memory for recently heard melodic patterns.

PMID- 10946539
TI  - Hypermnesia: age-related differences between young and older adults.
AB  - Hypermnesia is a net improvement in memory performance that occurs across tests
      in a multitest paradigm with only one study session. Our goal was to identify
      possible age-related differences in hypermnesic recall. We observed hypermnesia
      for young adults using verbal (Experiment 1) as well as pictorial (Experiment 2)
      material, but no hypermnesia for older adults in either experiment. We found no
      age-related difference in reminiscence (Experiments 1 and 2), though there was a
      substantial difference in intertest forgetting (Experiments 1 and 2). Older,
      relative to young, adults produced more forgetting, most of which occurred
      between Tests 1 and 2 (Experiments 1 and 2). Furthermore, older, relative to
      young, adults produced more intrusions. We failed to identify a relationship
      between intrusions and intertest forgetting. We suggest that the age-related
      difference in intertest forgetting may be due to less efficient reinstatement of
      cues at test by older adults. The present findings reveal that intertest
      forgetting plays a critical role in hypermnesic recall, particularly for older
      adults.

PMID- 10946540
TI  - An experimental study of strategy development.
AB  - Three experiments are reported in which the strategy usage for a compass point
      directions task was investigated. For this task, people may use either an
      efficient cancellation strategy or an inefficient spatial strategy (see Roberts,
      Gilmore, & Wood, 1997). Experiment 1, together with Experiment 2, showed that
      users of cancellation are unlikely to have explicit prior knowledge of this
      strategy; instead they discover it as a result of experience with the task.
      Experiment 1 also showed that strategy selection is unlikely to be based on
      stylistic preferences, and that reducing the cognitive demands of the task does
      not increase the discovery of cancellation. Experiment 3 showed that evaluation
      of strategy validity is also of importance: Unsuccessful evaluation may prevent
      the selection of a newly discovered strategy, even if it is the more efficient
      method.

PMID- 10946541
TI  - Judgment heuristics and recognition memory: prime identification and target
      processing fluency.
AB  - In three experiments, the effect of identification of a briefly presented word
      (prime) on a subsequent recognition response to that word (target) was
      investigated. Theories of current processing fluency (e.g., Jacoby & Whitehouse,
      1989) suggest that prime identification should reduce P(old) relative to prime
      misidentification because awareness of the prime provides a source to which to
      attribute target fluency, rendering attributions to prior presentation less
      likely. However, counter to these predictions, Experiment 1 demonstrated that
      prime identification increased P(old) relative to misidentified primes. It is
      hypothesized that this reversed effect was due to participants' using a heuristic
      that related prime identification success to prior presentation but was not based
      on current processing fluency. In Experiment 2, participants were induced to
      avoid using this heuristic by making an alternate source for prime identification
      success (display duration) highly available. Under these circumstances, prime
      identification reduced P(old) relative to prime misidentification, suggesting
      that participants now relied on current processing fluency rather than on prime
      identification success. Experiment 3 replicated the results of Experiments 1 and
      2, but with fixed rather than variable prime displays.

PMID- 10946542
TI  - The role of part-whole information in reasoning about relative size.
AB  - Models of comparative judgment have assumed that relative magnitude is computed
      from knowledge about absolute magnitude rather than retrieved directly. In
      Experiment 1, participants verified the relative size of part-whole pairs (e.g.,
      tree-leaf) and unrelated controls (e.g., tree-penny). The symbolic distance
      effect was much smaller for part-whole pairs than for unrelated controls. In two
      subsequent experiments, participants determined either which of two objects was
      closer in size to a third object or which of two pairs had a greater difference
      in the size of its constituents. In contrast to the paired comparison task in
      Experiment 1, judgments of part-whole items were more sensitive to the influence
      of symbolic distance than were unrelated controls. The fact that the part-whole
      relation attenuates the effects of symbolic distance in a paired comparison task
      but not in tasks that require an explicit comparison of size differences suggests
      that the part-whole relation provides a source of information about relative
      magnitude that does not depend on knowledge about absolute magnitude.

PMID- 10946543
TI  - Costs and benefits in perceptual categorization.
AB  - Observers categorized perceptual stimuli when the category costs and benefits
      were manipulated across conditions, and costs were either zero or nonzero. The
      cost-benefit structures were selected so that performance across conditions was
      equivalent with respect to the optimal classifier. Each observer completed
      several blocks of trials in each of the experimental conditions, and a series of
      nested models was applied to the individual observer data from all conditions. In
      general, performance became more nearly optimal as observers gained experience
      with the cost-benefit structures, but performance reached asymptote at a
      suboptimal level. Observers behaved differently in the zero- and nonzero-cost
      conditions, performing consistently worse when costs were nonzero. A test of the
      hypothesis that observers weight costs more heavily than benefits was
      inconclusive. Some aspects of the data supported this differential weighting
      hypothesis, but others did not. Implications for current theories of cost-benefit
      learning are discussed.

PMID- 10946544
TI  - Internal languages of retrieval: the bilingual encoding of memories for the
      personal past.
AB  - In contrast to most research on bilingual memory that focuses on how words in
      either lexicon are mapped onto memory for objects and concepts, we focus on
      memory for events in the personal past. Using a word-cue technique in sessions
      devoted exclusively to one language, we found that older Hispanic immigrants who
      had come to the United States as adults internally retrieved autobiographical
      memories in Spanish for events in the country of origin and in English for events
      in the U.S. These participants were consistently capable of discerning whether a
      memory had come to them "in words" or not, reflecting the distinction between
      purely imagistic or conceptual memories and specifically linguistic memories. Via
      examination of other phenomenological features of these memories (sense of re
      living, sensory detail, emotionality, and rehearsal), we conclude that the
      linguistic/nonlinguistic distinction is fundamental and independent of these
      other characteristics. Bilinguals encode and retrieve certain autobiographical
      memories in one or the other language according to the context of encoding, and
      these linguistic characteristics are stable properties of those memories over
      time.

PMID- 10946545
TI  - Memory and judgment: availability versus explanation-based accounts.
AB  - Two theories about the relationship between memory and decisions are examined. In
      an explanation-based model, the organization in memory of decision-relevant
      information determines decisions. In an availability model, the amount of
      information sampled from memory that supports competing decisions is crucial. In
      Experiment 1, subjects read evidence from a legal trial, made decisions, and
      provided free-recall data. Evidence presentation order was manipulated to produce
      differences in evidence coherence. When the prosecution evidence order was
      coherent, the subjects were more likely to choose guilty verdicts, and recall of
      prosecution evidence, relative to defense evidence, was greater. Thus, both
      evidence coherence and availability of information in memory could account for
      the basic findings. In Experiment 2, recall differences were eliminated as a
      function of evidence order. The results show that verdict effects favoring the
      more coherent prosecution evidence are obtained even when the relative amounts of
      prosecution and defense recall are equated across conditions.

PMID- 10946547
TI  - When does inconsistency hurt? On the relation between phonological consistency
      effects and the reliability of sublexical units.
AB  - Phonological consistency describes to what extent a letter string in one word is
      pronounced equally in other words. Phonological reliability describes to what
      extent a sublexical unit is usually consistent throughout a language. The
      relationship between the two concepts was investigated by comparing five
      sublexical units (onset-consonants, vowel, end-consonants, and the concatenation
      of the vowel with begin- or end-consonants) in Dutch and English with respect to
      their reliability and to how their consistency was related to naming errors and
      latencies. In a regression analysis, naming latencies and errors on genuine Dutch
      words (consistent) and imported words (inconsistent) were predicted by the
      phonological consistency of the five units. The same was done for two sets of
      English naming data. Consistency had a much stronger effect in Dutch than in
      English naming studies when all five units were considered. The special role of
      the vowel plus end-consonants, which has been found in English naming data, could
      not be demonstrated in Dutch. In both languages, the size of consistency effects
      mirrors the reliability of the five units.

PMID- 10946546
TI  - Semantic priming in the prime task effect: evidence of automatic semantic
      processing of distractors.
AB  - The automaticity of the semantic processing of words has been questioned because
      of the reduction of semantic priming when the prime word is processed
      nonsemantically--for example, in letter search (the prime task effect). In two
      experiments, prime distractor words produced semantic priming in a subsequent
      lexical decision task, but with the direction of priming (positive or negative)
      depending on the prime task. Lexico-semantic tasks produced negative semantic
      priming, whereas letter search produced positive semantic priming. These results
      are discussed in terms of task-based inhibition. We argue that, given the results
      from the distractors, the absence of semantic priming does not indicate an
      absence of semantic activation but reflects the action of control processes on
      prepotent responses when less practiced responses are needed.

PMID- 10946548
TI  - Turning an advantage into a disadvantage: ambiguity effects in lexical decision
      versus reading tasks.
AB  - When performing a lexical decision task, participants can correctly categorize
      letter strings as words faster if they have multiple meanings (i.e., ambiguous
      words) than if they have one meaning (i.e., unambiguous words). In contrast, when
      reading connected text, participants tend to fixate longer on ambiguous words
      than on unambiguous words. Why are ambiguous words at an advantage in one word
      recognition task, and at a disadvantage in another? These disparate results can
      be reconciled if it is assumed that ambiguous words are relatively fast to reach
      a semantic-blend state sufficient for supporting lexical decisions, but then slow
      to escape the blend when the task requires a specific meaning be retrieved. We
      report several experiments that support this possibility.

PMID- 10946549
TI  - Effects of headings and familiarity with a text on strategies for searching a
      text.
AB  - College students were videotaped while they searched chapter-length texts for
      answers to specific questions. The texts either did not contain headings or
      contained one of three types of headings that varied in the information that they
      provided about text organization and content. Familiarity with the text was
      varied by manipulating (1) the number of prior searches of the text and (2)
      whether or not the text was read before searching. Measures were taken of the
      time spent examining each page and of the sequence of examination of pages.
      Cluster analyses of the search measures revealed that familiarity with the text
      influenced a searcher's strategy for selecting which pages to examine. Once a
      page was selected for examination, both headings and familiarity influenced how
      the page was inspected.

PMID- 10946550
TI  - Writing words from pictures: what representations are activated, and when?
AB  - In three experiments, the nature of the representations involved in written
      picture naming and the time course of their activation were investigated. French
      participants had to produce picture names while hearing distractors. In
      Experiment 1, distractors semantically related to the picture names yielded a
      semantic interference effect when a stimulus onset asynchrony (SOA) of--150 msec,
      but not when a SOA of 0 msec, was used, in both spoken and written picture
      naming. Experiment 2 showed that the semantic interference effect was not located
      at the conceptual level. In Experiment 3, participants wrote down picture names
      while hearing semantically related, phonologically related, both semantically and
      phonologically related, or unrelated distractors, presented at both SOAs. A
      semantic interference effect was obtained with phonologically unrelated
      distractors but was eliminated with phonologically related distractors.
      Facilitatory effects of phonologically related distractors were found at both
      SOAs. The implications of the findings for written picture naming are discussed.

PMID- 10946551
TI  - [Efficacy of endoscopic transethmoidal.transsphenoidal surgery for pituitary
      tumors].
AB  - Endoscopic transethmoidal.transsphenoidal surgery was performed on 30 patients
      with pituitary tumors, and the usefulness of this procedure was evaluated. As
      with conventional endoscopic intranasal surgery, the ethmoidal sinuses were
      opened and a broad window was created in the ethmoidal sinus from the directions
      of the middle meatus and the olfactory cleft. Then an endoscopic washing device
      was attached to a 0 degree or 30 degrees rigid endoscope and it was immobilized
      in the left nasal cavity with an endoscope immobilization apparatus. Removal of
      the tumor was then started from the right side by a bimanual technique. Based on
      the results, this surgical procedure was judged to be useful for the following
      reasons (1) it makes it easy to carry out the operative manipulations even in a
      narrowed nasal cavity, thereby reducing the overall time required for surgery,
      and (2) it is possible to prevent postoperative deformities of the nasal cavity
      morphology caused by pressure on its lateral wall. In additional, (3) the
      surgical wound can be observed, and CSF leakage can be repaired immediately after
      completion of the operation. Corrective surgery can be performed on an outpatient
      basis early after the initial operation to correct postoperative deformities of
      the nasal paranasal cavities, which might later cause nasal obstruction or an
      olfactory disturbance. Finally, (4) employing the route of endoscopic
      transethmoidal.transsphenoidal surgery facilitates the performance of a second
      operation soon, or even several months, after the first operation. A second
      operation may be necessary in the event of recurrence of the pituitary tumor or
      complication by chronic sinusitis. On the basis of our experience in the this
      study, we conclude that our method of endoscopic transethmoidal.transsphenoidal
      surgery will be useful for reducing invasiveness in the nasal cavities and
      achieving maximum prevention of postoperative complications. In order to fulfill
      its potential, neurosurgeons will need to master forceps techniques in the visual
      field provided by the endoscope and to cooperate with otorhinologists who are
      skilled in endoscopic techniques.

PMID- 10946552
TI  - [A study of the pathogenesis of tonsillar focal infection--transplantation of
      human tonsillar lymphocytes and human skin into SCID mice].
AB  - Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical
      tonsillar focal infections, based on the marked clinical improvement of the skin
      lesions after tonsillectomy. In early-stage of PPP, it has been reported that
      lymphocytes, predominantly CD4-positive cells, infiltrate the palmar and plantar
      skin. However, the origin and mechanism of infiltration by these lymphocytes is
      not clear and there are very few reports on whether tonsillar cells react
      directly with the skin, possibly due to the difficulty of establishing adequate
      animal models. In this study, we established an experimental animal model of mice
      with severe combined immunodeficiency (SCID) and observed the reactions of the
      tonsillar lymphocytes (TL) or peripheral blood lymphocytes (PBL) of patients with
      PPP to their own plantar skin by transplanting the lymphocytes and skin of the
      patient into the mice. The results revealed that TL infiltrated the skin to a
      significantly greater extent than PBL. Most of these lymphocytes were T
      lymphocytes, and no B lymphocytes were detected in the transplanted skin. Strong
      expression of LFA-1 and ICAM-1 was observed in the skin after the TL
      transplantation. These results suggest that TL have a strong affinity for the
      skin in PPP, and that the adhesion molecules may play an important role in the
      infiltration by lymphocytes of the skin.

PMID- 10946553
TI  - [Treatment strategy for cervical node metastasis from squamous cell carcinoma of
      the oropharynx].
AB  - The purpose of this study is to ascertain the role of neck surgery and radiation
      therapy for cervical lymph node metastasis in oropharyngeal cancer patients. We
      reviewed 217 previously untreated patients with squamous cell carcinoma of the
      oropharynx who were treated at the Cancer Institute Hospital in Tokyo between
      1971 and 1995. The N stage distribution was; N0: 83(38.2%), N1: 42(19.4%), N2a:
      23(10.6%), N2b: 27(12.4%), N2c: 33(15.2%), and N3: 9(4.2%). A predominance of
      cervical node metastases in level II and III was revealed and there were no skip
      metastases outside of level II and III. The control rate of cervical metastasis
      for each N stage was; N0: 96.9%, N1: 90.0%, N2a: 76.5%, N2b: 62.5%, N2c: 50.0%,
      and N3: 0%. Definitive irradiation provided sufficient treatment for small nodes,
      when the primary tumor growth was well controlled by radiation therapy. Neck
      dissection was necessary for more advanced neck metastases. Selective limited
      neck dissection (level II and III) is recommended for N0 and N1 patients, and
      modified or classical RND is considered to be better for most cases with N2 and
      N3.

PMID- 10946554
TI  - [Ultrasonographic evaluation of metastatic cervical lymph nodes in head and neck
      cancers].
AB  - This study evaluates the use of ultrasonography (USG) to diagnose metastatic
      cervical lymph nodes. Three-hundred and one lymph nodes were removed from 58
      patients with squamous cell carcinomas of the head and neck. None of the patients
      had received any preoperative treatments for cancer. The lymph nodes were then
      histopathologically examined: 139 metastatic lymph nodes and 162 non-metastatic
      nodes were found. USG was then used to evaluate the size, internal echo, and
      margin of each lymph node. Size was found to be the best criteria for
      distinguishing metastatic lymph nodes from non-metastatic lymph nodes in all
      cervical regions (78% accuracy). Superior internal jugular lymph nodes and
      submandibular lymph nodes larger than 7 mm and mid and inferior internal jugular
      lymph nodes larger than 6 mm were regarded as metastatic. Internal echoes were
      classified into five patterns: homogeneous hypoechoic, homogeneous hyperechoic,
      heterogeneous, eccentric hyperechoic, and centric hyperechoic. Homogeneous
      hyperechoic and heterogeneous patterns were characteristic of metastatic nodes,
      while eccentric hyperechoic patterns were characteristic of non-metastatic nodes.
      Homogeneous hypoechoic patterns were observed in both metastatic and non
      metastatic nodes. Regular margins were found in 81% of the metastatic nodes. Of
      the 22 lymph nodes with irregular margins, however, 91% were metastatic.
      Evaluations using a combination of USG and clinical feature criteria were
      compared with evaluations using only thickness as a criterium. Although thickness
      is the single most important factor in diagnosing metastatic nodes, the
      combination of USG and clinical feature criteria improved the accuracy of
      diagnosis to 83%. Thus, diagnostic methods involving a combination of several
      criteria are more accurate than methods involving only a single criterium.

PMID- 10946556
TI  - [IL-1 and TNF-alpha-mediated regulation of IL-6, IL-8, and GM-CSF release from
      cultured nasal epithelial cells].
AB  - IL-6, IL-8 and GM-CSF regulate inflammatory cell infiltration and survival at
      sites of inflammation. IL-1, TNF-alpha, IL-6, IL-8 and GM-CSF have been reported
      to be released from cultured nasal epithelial cells (CNEC). Here, focusing on IL
      1 and TNF-alpha as key cytokines, we examined whether these two cytokines could
      regulate the release of IL-6, IL-8 and GM-CSF from CNEC. CNEC were treated with
      antibodies to IL-1 alpha and TNF-alpha at various doses for a period of 48 hrs.
      The levels of IL-6, IL-8 and GM-CSF in the culture supernatants were then
      estimated by ELISA. Treatment of CNEC with antibodies to IL-1 alpha and TNF-alpha
      inhibited the release of IL-6, IL-8 and GM-CSF from them in a dose-dependent
      manner. The inhibition of IL-6 and GM-CSF release was significantly greater after
      treatment of the CNEC with the antibodies to IL-1 alpha. Furthermore CNEC
      expressed IL-1 receptors and TNF receptors. These results suggest that the
      epithelial cell-derived IL-1 alpha and TNF-alpha can regulate the release of
      other cytokines like IL-6, IL-8 and GM-CSF in an autocrine manner.

PMID- 10946555
TI  - [Antitumor effect of the angiogenesis inhibitor, TNP470, on squamous cell
      carcinoma cells in head and neck cancer].
AB  - The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl
      carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro
      and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470
      reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody
      (Ab.) The combination of anti-IL-8 Ab (10 micrograms/ml) and TNP470 (10 ng/ml)
      significantly inhibited the proliferation of KB cells, compared to no treatment
      (p < 0.05). Proliferation of KB cells was also significantly more suppressed by
      simultaneous treatment of cisplatin and TNP470 (1 mg/ml), than cisplatin alone.
      The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti
      vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by
      different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and
      intravenous. TNP470 (10 mg/ml) showed an antitumor effect, and intratumoral
      administration of TNP470 was the most effective route. Combined administration of
      anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab
      alone did. These results suggest that the combination of TNP470, cisplatin, and
      anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and
      neck.

PMID- 10946557
TI  - [An office technique for myringoplasty without the use of fibrin glue].
AB  - A simple method for office closure of eardrum perforation using an atero-collagen
      graft used for dermal defects (Terdermis) without fibrin glue was developed.
      Eardrum perforations were successfully closed in 71.4% of all cases (63 ears)
      after the initial treatment. Neither skin incision nor the use of temporal
      fascial grafts was necessary in this method. The merit of the method is that
      there is no possibility of blood infection because no blood materials are used.

PMID- 10946558
TI  - [Nasopharyngeal stenosis after uvulopalatopharyngoplasty].
AB  - We report a case of nasopharyngeal stenosis after uvulopalatopharyngoplasty
      (UPPP). A 42-year-old man underwent UPPP because of severe snoring. Two months
      later, a severe nasopharyngeal stenosis was observed upon examination. The
      stenosis was caused by the adhesion of the soft palate to the posterior
      pharyngeal scar. X-ray examination of the patient's pharynx revealed that the
      postoperative nasopharyngeal stenosis may have also been caused by the depth of
      the pharynx, in addition to the morphological anomaly. To avoid velopharyngeal
      insufficiency and nasopharyngeal stenosis, careful examination of the pharynx
      prior to surgery is highly recommended.

PMID- 10946559
TI  - Regulation of mineral and trace elements in human milk: exogenous and endogenous
      factors.
AB  - Breast-fed infants are dependent on an adequate supply of minerals and trace
      elements for normal growth and development. For most of these elements, the
      mammary gland appears to have developed mechanisms to regulate their
      concentrations, even when the maternal diet varies considerably or maternal
      conditions are affected by different challenges. For some elements, however,
      there appears to be little or no such regulation. Increased knowledge about these
      mechanisms, or their absence, and to what extent they may compensate for adverse
      maternal conditions, including poor nutrition, will help identify infants and
      women at risk for deficiencies of these nutrients.

PMID- 10946561
TI  - Importance of diet in maternal phenylketonuria.
AB  - Diet has long been recognized as the primary treatment modality for individuals
      with phenylketonuria (PKU) during infancy and childhood. Recent findings from the
      Maternal PKU Collaborative Study clearly indicate that dietary restriction of
      phenylalanine is also necessary to prevent the adverse effects of an elevated
      plasma phenylalanine concentration during pregnancy, which include microcephaly,
      physical anomalies, and mental retardation.

PMID- 10946560
TI  - A gene knockout corroborates the integral function of cellular retinol-binding
      protein in retinoid metabolism.
AB  - Continually expanding evidence has moved inexorably toward establishing key
      functions for cellular retinol-binding protein (CRBP) in retinoid metabolism.
      These experimental data integrate into a model of CRBP as a chaperone that
      protects retinol from the cellular milieu and interacts with certain retinoid
      metabolizing enzymes. Mutant mice with an inactivated CRBP gene show decreased
      liver retinyl ester storage, a shorter elimination half-life of liver retinoids,
      and predisposition to vitamin A deficiency. No morphologic phenotype was observed
      until vitamin A was exhausted. Although the mechanisms underlying diminished
      vitamin A in the CRBP-null mice have not been elucidated, the observations
      support the model of CRBP as a chaperone of retinoid metabolism.

PMID- 10946562
TI  - Passive smoking induces oxidant damage preventable by vitamin C.
AB  - The deleterious effects of cigarette smoking on antioxidant protection and
      chronic disease risk are well known. Recent studies show that exposure of
      nonsmokers to environmental tobacco smoke results in increased oxidant damage
      linked to heart and respiratory diseases. The new findings provide support for
      efforts to minimize exposure of nonsmokers to environmental tobacco smoke and
      oxidizing air pollutants and demonstrate the importance of vitamin C for
      antioxidant protection.

PMID- 10946563
TI  - Nutrition support for individuals with liver failure.
AB  - The prevalence of liver diseases is increasing in the United States, particularly
      as a result of the recent hepatitis C epidemic. In the past, patients who
      developed fulminant hepatic failure or cirrhosis owing to a chronic liver disease
      were likely to expire. During the last 15-20 years, liver transplantation has
      given these patients a chance at survival. Progressive nutrition deficiencies and
      muscle wasting are universal problems in these patients. Left untreated, the
      progressive wasting of liver disease leads to infection and an increased risk of
      death owing to infection both before and after transplantation. Aggressive
      nutritional support is essential to optimize the care of these patients and to
      enable them to obtain and survive a liver transplant and gain access to a new
      life following a successful liver engraftment.

PMID- 10946564
TI  - The complicated research field of nutrients and osteoporosis.

PMID- 10946565
TI  - Iodized salt.

PMID- 10946566
TI  - Study of nonlinear optical properties of multilayer Langmuir-Blodgett films
      containing bacteriorhodopsin.
AB  - Multilayer oriented Langmuir-Blodgett films of bacteriorhodopsin were prepared
      and their nonlinear optical properties, including second harmonic generation and
      photoresponse at a two phase-modulated beams mixing, were investigated. The
      nonlinear component of refractive index of the films was measured.

PMID- 10946567
TI  - Reactions of psoralen radical cations with biological substrates.
AB  - The reactions of several psoralen and coumarin radical cations with biological
      substrates such as nucleotides, amino acids and alkenes that serve as models for
      unsaturated fatty acids have been examined. The radical cations were generated by
      laser photoionization of the parent psoralen or coumarin in aqueous buffer in
      most cases. Easily oxidized substrates such as tyrosine, tryptophan and guanosine
      monophosphate react with the 8-methoxypsoralen and several methoxy-substituted
      coumarin radical cations with rate constants in excess of 2 x 10(9) M-1 s-1. In
      each case reaction occurs via electron transfer, as demonstrated by the
      observation of quencher-derived radical cations or radicals by transient
      absorption spectroscopy. For other substrates such as histidine, methionine and
      adenosine monophosphate the measured rate constants are significantly slower and
      vary with the oxidation potential of both the parent psoralen or coumarin and the
      quencher, again indicative of electron transfer reactivity. Most of the alkenes
      studied also react with the psoralen or coumarin radical cations via electron
      transfer, although there is some evidence for addition for linoleic acid. Product
      studies carried out using both lamp and laser irradiation in the presence of
      deoxyguanosine as a radical cation trap lead to the formation of characteristic
      base-derived Type-I (electron transfer) products. This lends support to our
      previous hypothesis that photoionization occurs via a monophotonic process and is
      thus relevant to conditions used in clinical phototherapeutic applications of
      psoralens. The results demonstrate the relevance of electron transfer chemistry
      to the use of psoralens and related compounds as photoactivated drugs.

PMID- 10946568
TI  - Photodecarboxylation of ketoprofen in aqueous solution. A time-resolved laser
      induced optoacoustic study.
AB  - The photodecarboxylation reaction of 2-(3-benzoylphenyl)propionate (ketoprofen
      anion, KP-) was studied in water and in 0.1 M phosphate buffer solutions in the
      pH range 5.7-11.0 by laser-induced optoacoustic spectroscopy (LIOAS, T range 9.5
      31.6 degrees C). Upon exciting KP- with 355 nm laser pulses under anaerobic
      conditions, two components in the LIOAS signals with well-separated lifetimes
      were found (tau 1 < 20 ns; 250 < tau 2 < 500 ns) in the whole pH range, whereas a
      long-lived third component (4 < tau 3 < 10 microseconds) was only detected at pH
      < or = 6.1. The heat and structural volume changes accompanying the first step
      did not depend on pH or on the presence of buffer. The carbanion resulting from
      prompt decarboxylation within the nanosecond pulse (< 10 ns) drastically reduces
      its molar volume ([-18.9 +/- 2.0] cm3/mol) with respect to KP- and its enthalpy
      content is (256 +/- 10) kJ/mol. At acid pH (ca 6), a species is formed with a
      lifetime in the hundreds of ns. The enthalpy and structural volume change for
      this species with respect to KP- are (181 +/- 15) kJ/mol and (+0.6 +/- 2.0)
      cm3/mol, respectively. This species is most likely a neutral biradical formed by
      protonation of the decarboxylated carbanion, and decays to the final product 3
      ethylbenzophenone in several microsecond. At basic pH (ca 11), direct formation
      of 3-ethylbenzophenone occurs in hundreds of ns involving a reaction with the
      solvent. The global decarboxylation reaction is endothermic ([45 +/- 15] kJ/mol)
      and shows an expansion of (+14.5 +/- 0.5) cm3/mol with respect to KP-. At low pH,
      the presence of buffer strongly affects the magnitude of the structural volume
      changes associated with intermolecular proton-transfer processes of the long
      lived species due to reactions of the buffer anion with the decarboxylated
      ketoprofen anion.

PMID- 10946569
TI  - A theoretical approach of the measurement of osmotic fragility of erythrocytes by
      optical transmission.
AB  - The osmotic fragility of the erythrocyte membrane to hypotonic solutions is
      investigated theoretically. The fragility curves exhibit a strong transmittance
      rise. This variation is assumed to result from changes in the scattering
      properties of erythrocytes under dialysis resulting from swelling and hemolysis.
      The refractive indices of erythrocytes are obtained through the Lorentz-Lorenz
      relation based on hemoglobin and water contents. The scattering cross sections
      (needed to calculate the collimated transmittance) and the forward scattered
      intensity (needed to calculate the incoherent transmittance) are expressed
      according to the simple algebraic relations of the anomalous diffraction
      approximation. It is shown that swelling (or shrinking) has no influence on the
      collimated transmittance. Hemolysis alone causes the abrupt sigmoidal increase of
      the collimated transmittance with time. The possible transmittance increase
      (decrease) observed during swelling (shrinking) is due to incoherent
      transmittance and depends on the detecting solid angle value of the experimental
      setup.

PMID- 10946570
TI  - Effect of solvent-water mixtures on the prototropic equilibria of fluorescein and
      on the spectral properties of the monoanion
AB  - A spectral resolution procedure was used to resolve the absorption, excitation
      and emission spectra of the fluorescein monoanion in a number of solvent-water
      mixtures. This permitted an analysis of the effect of the solvent environment on
      the spectral properties of the monoanion and on the lactone/monoanion/dianion
      transitions of fluorescein. The monoanion excitation and emission spectra show
      relatively small changes with changing environment, a behavior that is related to
      the hydrogen-bonding environment of the solvent-water mixtures. There is also a
      general increase in the quantum yield of the monoanion from 0.36 in water to
      values up to 0.49 in the solvent-water mixtures. The presence of solvent also
      results in a general increase in the lactone content and in the monoanion:dianion
      and lactone:monoanion ratios. General polarity effects alone cannot account for
      the observed effects on the prototropic transitions indicating that specific
      solute-solvent effects involving hydrogen bonding perturb the prototropic
      equilibria of fluorescein.

PMID- 10946571
TI  - Phototransformations of 5-aminolevulinic acid-induced protoporphyrin IX in vitro:
      a spectroscopic study.
AB  - Human adenocarcinoma cells of the line WiDr were incubated with 5-aminolevulinic
      acid to induce protoporphyrin IX (PpIX) and then exposed to laser light of
      wavelength 635 nm. The PpIX fluorescence decreased with increasing exposure. The
      decay rate was slightly dependent on the initial PpIX concentration. The PpIX
      fluorescence was halved by a fluence of about 40 J/cm2. Several fluorescing
      photoproducts were formed. The main one, supposedly the chlorine-type
      photoprotoporphyrin (Ppp), had a fluorescence excitation spectrum stretching out
      to about 680 nm with a maximum at around 668 nm. The formation kinetics of this
      product was dependent on the initial PpIX concentration. Moreover, it was
      selectively bleached by exposure to light at 670 nm. A photoproduct with an
      emission maximum at 652 nm, different from Ppp, remained after this exposure.
      Traces of a photoproduct(s) with fluorescence emission slightly blue-shifted
      compared with that of PpIX, supposedly water-soluble porphyrins, were also
      detected after light exposure.

PMID- 10946572
TI  - Variability of bio-optical factors influencing the seasonal attenuation of
      ultraviolet radiation in temperate coastal waters of Japan
AB  - The study identifies the relative contribution of various bio-optical factors to
      the total attenuation of ultraviolet radiation (UVR) wavelengths and
      photosynthetically active radiation (PAR) in temperate coastal waters of Japan by
      surveying the physical properties of the water column, UVR and PAR penetration,
      and the absorption characteristics of dissolved and particulate material.
      Spectral absorbance properties of pigment (aph), detritus (ad) and chromophoric
      dissolved organic material (aCDOM) displayed both seasonal and wavelength
      specific variability. On an annual basis, absorbance by aCDOM was the highest
      absorbing fraction (47-59%) for the UVR wavelengths measured (305, 320, 340 and
      380 nm) but decreased (32%) at 450 nm. Contribution of pigments to total
      absorbance was highest (40-60%) during a spring bloom for both UVR and PAR. A
      large variability (C.V. > 42%) for annual average attenuation coefficients
      (Kd[lambda]) at respective wavelengths observed suggests that the spectral
      composition of the water column changes throughout the year in this region. A
      significant relationship was observed between Kd(lambda) and aCDOM at 305, 320,
      340 and 380 nm only (P < 0.01) but not for 450 nm (PAR) indicating the role of
      CDOM in regulating variations in Kd(lambda), particularly in the UVR range. The
      slope S, obtained from a natural-log plot of the absorption coefficient of CDOM
      against wavelength, ranged between 0.014 and 0.036 nm-1 annually (average = 0.020
      +/- 0.007, C.V. = 35%) and suggests seasonal changes in the origin of CDOM
      between terrestrial (low S) and biogenous (high S) CDOM.

PMID- 10946573
TI  - Photooxidation of lens alpha-crystallin by hypericin (active ingredient in St.
      John's Wort).
AB  - Hypericin is the active ingredient in the over the counter antidepressant
      medication St. John's Wort. Hypericin produces singlet oxygen and other excited
      state intermediates that indicate it should be a very efficient phototoxic agent
      in the eye. Furthermore it absorbs in the UV and visible range, which means it
      can potentially damage both the lens and the retina. Lens alpha-crystallin,
      isolated from calf lenses, was irradiated in the presence of hypericin (5 x 10(
      5) M, 10 mM ammonium bicarbonate, pH 7.0) and in the presence and absence of
      light (> 300 nm, 24 mW/cm2). Hypericin-induced photosensitized
      photopolymerization as assessed by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis. Further analysis of the oxidative changes occurring in alpha
      crystallin using mass spectrometry showed specific oxidation of methionine,
      tryptophan and histidine residues, which increased with irradiation time.
      Hypericin did not damage the lens protein in the dark. Damage to alpha-crystallin
      could undermine the integrity of the lens directly by protein denaturation and
      indirectly by disturbing chaperone function. Therefore, in the presence of light,
      hypericin can induce changes in lens protein that could lead to the formation of
      cataracts. Appropriate precautions should be taken to protect the eye from
      intense sunlight while on this antidepressant medication.

PMID- 10946574
TI  - Photophysical consequences of coupling bacteriochlorophyll a with serine and its
      resulting solubility in water.
AB  - We investigated the dependence on solvents of optical absorption and emission of
      the bacteriochlorophyll a-serine (BChl-ser), a water soluble bacteriochlorophyll
      (BChl) derivative. Comparison between the experimental data and those collected
      for BChl in nonaqueous solvents shows that only a minor interaction takes place
      between serine and the macrocycle's pi-electron system. Nevertheless, the
      coupling with serine results in a small enhancement of the nonradiative
      relaxation rate from the first excited singlet state S1. In buffered aqueous
      solution (pH = 7.4), the Stokes shift of the BChl-ser fluorescence and its
      nonradiative relaxation rate are enhanced compared with those in nonaqueous
      solutions (Scherz, A., S. Katz, Y. Vakrat, V. Brumfeld, E. Gabelmann, D. Leupold,
      J. R. Norris, H. Scheer and Y. Salomon (1998) Photosynthesis: Mechanisms and
      Effects, Vol. V (Edited by G. Garab), pp. 4207-4212. Kluwer Academic,
      Dordrecht.), probably as a result of a hydrogen bonding between the BChl
      macrocycle and the water molecules. In aprotic solvents, without hydrogen bonds,
      the permanent dipole moment of the first excited singlet state in both BChl and
      BChl-ser is increased compared with the ground state by at least 2.5 Debye.

PMID- 10946575
TI  - Light-induced apoptosis involves a defined sequence of cytoplasmic and nuclear
      calcium release in AlPcS4-photosensitized rat bladder RR 1022 epithelial cells.
AB  - Oxidative stress induced by light activation of photosensitizers is regarded to
      have a role in triggering cell death pathways during photodynamic therapy (PDT).
      Reactive oxygen species have been proposed to act as signal transduction
      molecules activating downstream reactions that lead to apoptosis. Mainly debated
      is the cooperating role of other signaling systems like calcium or pH. The
      present work contributes to this discussion by studying PDT effects in cell
      cultures of rat bladder epithelial cells for the hydrophilic tetrasulfonated
      aluminum phthalocyanine (AlPcS4). Cells were coincubated with the photosensitizer
      and the calcium-sensitive probe Fluo-3. The light-induced reactions were analyzed
      with a confocal laser scanning microscope. The dynamics of the process during
      light activation was observed with subcellular resolution. A transient calcium
      elevation during the irradiation process was detected, especially in the cell's
      nuclei, followed by a more sustained increase. The evaluation of the energy-dose
      dependent phototoxicity after an incubation time with the photosensitizer of 1
      and 24 h, showed enhanced phototoxicity when the drug was present for 24 h.
      Surprisingly, stimulation of cell proliferation was observed at very low light
      doses (at 0.2 J/cm2) when the drug was incubated for 24 h (cell viability 160%).
      Induction of apoptosis could be observed after irradiation with fluences between
      1 and 3 J/cm2. Apoptotic cells were identified with fluorescein isothiocyanate
      labeled Annexin V, which binds to phosphatidylserine after its translocation to
      the outer plasma membrane. In the presence of the antioxidant
      pyrrolidinedithiocarbamate the transient calcium elevation was totally inhibited,
      as was the subsequent translocation of PS. In contrast, N-acetyl-L-cysteine did
      not suppress the transient calcium increase. Our data might be consistent with
      calcium regulated processes during AlPcS4-PDT and the involvement of oxygen
      radicals.

PMID- 10946576
TI  - meso-tetraphenylporphyrin dimer derivatives as potential photosensitizers in
      photodynamic therapy. Part 2.
AB  - Studies on the synthesis, singlet oxygen and fluorescence yields and
      pharmacokinetic properties of three different dimeric porphyrins with an amide
      linkage (D2-D4) are described and compared with the results recently reported for
      a dimeric porphyrin (D1). The pharmacokinetic behavior of all dimers were
      examined in Balb/c mice bearing MS-2 fibrosarcomas. The maximal efficiency and
      selectivity of photosensitizer accumulation in each tumor tissue takes place at
      24 h after drug administration of 1.0 mg kg-1 into DL-alpha
      dipalmitoylphosphatidylcholine liposomes by intravenous injection. Since the
      dimeric porphyrins exhibit high quantum yields of singlet oxygen generation, long
      triplet lifetimes and high photostability, the results obtained suggest that the
      evaluated dimeric structures may be promising candidates for further use in PDT
      experiments. The results also allow the possibility to establish a correlation
      between the chemical structure of the dyes and the efficiency/selectivity of the
      tumor accumulation and can be used for building up optimal photosensitizing
      agents for tumors.

PMID- 10946577
TI  - Cell-type specific protoporphyrin IX metabolism in human bladder cancer in vitro.
AB  - 5-Aminolevulinic acid (ALA)-supported fluorescence endoscopy of the urinary
      bladder results in a detection rate of bladder cancer superior to that of white
      light endoscopy. The different accumulation of the metabolite protoporphyrin IX
      (PPIX) in tumor cells after ALA instillation is poorly understood; however, it is
      crucial to optimize diagnosis and potential phototherapy. For systematic analysis
      of cell-type specific PPIX accumulation and metabolism two human bladder
      carcinoma cell lines (RT4 and J82), a normal urothelial cell line (UROtsa), and a
      fibroblast cell line (N1) were chosen, and grown in two different growth states
      to model important tissue components of the urinary bladder, i.e. tumor, normal
      epithelium and stroma. To quantitate PPIX content, fluorescence intensities
      measured by flow cytometry were matched with cellular PPIX extraction values, and
      related to relative ferrochelatase activity, cellular iron content, number of
      transferrin receptors per cell and porphobilinogen deaminase (PBGD) activity. For
      in vitro experiments, the initial correlation of relative flow cytometric and
      spectrometric measurements of PPIX provides a calibration curve for consequent
      flow cytometric PPIX quantification. Lower fluorescence of normal cells could be
      explained by significant differences of ferrochelatase activity and iron content
      in comparison to tumor cells. However, the content of iron was not related to
      transferrin receptor content. PBGD activity seemed to play a minor role for the
      differential accumulation of PPIX in urothelial cells. In conclusion, the in
      vitro culture of urothelial cells and fibroblasts indicates that the most
      important metabolic step for PPIX accumulation in the urinary bladder is the
      transition from PPIX to heme. Further investigation of PPIX metabolism does
      support the validation of photodynamic diagnosis, and might also lead the way to
      a highly specific tumor related molecule.

PMID- 10946578
TI  - Macromolecular contrast agents for optical imaging of tumors: comparison of
      indotricarbocyanine-labeled human serum albumin and transferrin.
AB  - Macromolecules accumulate in solid tumors and can thus be used as carriers for
      the delivery of attached contrast agents to tumors. We report the synthesis and
      use of serum protein-dye conjugates consisting of transferrin (Tf) or human serum
      albumin (HSA) and an indotricarbocyanine (ITCC) derivative as contrast agents for
      the optical imaging of tumors. The compounds were characterized with respect to
      their photophysical properties and tested in vitro for their ability to bind to
      tumor cells and in vivo for their potential to delineate experimental tumors. In
      contrast to HAS-ITTC, Tf-ITCC showed receptor-mediated uptake by HT29 human colon
      cancer cells in vitro. After intravenous injection into HT29 tumor-bearing nude
      mice both compounds induced increased fluorescence contrast of tumors in vivo.
      After 24 h the contrast between tumor and normal tissue was significantly higher
      for Tf-ITCC than for HAS-ITCC. Dye-induced fluorescence was found to be
      predominantly located in perinecrotic areas of the tumor. Furthermore, Tf-ITCC
      produced fluorescence of viable tumor cells, whereas HAS-ITCC fluorescence was
      recorded along connective tissue. We conclude that ITCC-labeled Tf and HSA can
      serve as macromolecular contrast agents for the optical imaging of tumors, with
      Tf-ITCC showing higher efficiency.

PMID- 10946579
TI  - Optical detection of triggered atherosclerotic plaque disruption by fluorescence
      emission analysis.
AB  - Fluorescence emission analysis (FEA) has proven to be very sensitive for the
      detection of elastin, collagen and lipids, which are recognized as the major
      sources of autofluorescence in vascular tissues. FEA has also been reported to
      detect venous thromboemboli. In this paper we have tested the hypothesis that FEA
      can reproducibly detect in vivo and in vitro triggered plaque disruption and
      thrombosis in a rabbit model. Fluorescence emission (FE) spectra, recorded in
      vivo, detected Russell's viper venom (RVV)-induced transformation of
      atherosclerotic plaque. FE intensity at 410-490 nm 4 weeks after angioplasty was
      significantly lower (P < 0.0033 by analysis of variance) in RVV-treated rabbits
      when compared to control animals with stable plaque. FE spectral profile analyses
      also demonstrated a significant change in curve shape as demonstrated by
      polynomial regression analysis (R2 from 0.980 to 0.997). We have also
      demonstrated an excellent correlation between changes in FE intensity and the
      structural characteristics detected at different stages of "unstable
      atherosclerotic plaque" development using multiple regression analysis (R2 =
      0.989). Thus, FEA applied in vivo is a sensitive and highly informative
      diagnostic technique for detection of triggered atherosclerotic plaque disruption
      and related structural changes, associated with plaque transformation, in a
      rabbit model.

PMID- 10946580
TI  - UV exposure alters respiratory allergic responses in mice.
AB  - We have tested the hypothesis that exposure to ultraviolet light would inhibit T
      helper-1 (Th1) responses and stimulate T helper-2 (Th2) responses, and that thus
      in a mouse model of allergic (i.e. extrinsic) asthma (using ovalbumin [OVA] as
      the allergen) increased symptoms would be observed, while in a model of Th1
      dependent occupational asthma (in which picryl chloride is the allergen)
      decreased symptoms would be observed. Whereas reduced interferon (IFN)-gamma
      production, decreased inflammatory responses in the airways, and reduced airway
      reactivity to nonspecific stimuli were observed in UV-preexposed picryl chloride
      sensitized and challenged mice, the results in the OVA model were less clear.
      Increased interleukin (IL)-10 production as a result of UV exposure was observed,
      together with unchanged IL-4 and IFN-gamma. In addition, decreased OVA-specific
      immunoglobin, IgG1 and IgE, titers were noted, as well as decreased nonspecific
      airway hyperreactivity. Eosinophilic inflammatory responses were not influenced.
      The results indicate that UV exposure can have systemic effects that influence
      ongoing immune responses in the respiratory tract. The effects are not only
      restricted to immune responses that are predominantly Th1 dependent (i.e.
      pulmonary delayed-type hypersensitivity and IFN-gamma production in response to
      picryl chloride) but also to immune response that are predominantly Th2
      dependent, i.e. decreased specific IgE titers.

PMID- 10946581
TI  - Induction, distribution and repair of UV photodamage in the platyfish,
      Xiphophorus signum.
AB  - The genus Xiphophorus is an important model for investigating the etiology and
      genetics of sunlight-induced melanoma as well as other cancers. We used
      immunological techniques to determine the induction, distribution and repair of
      cyclobutane pyrimidine dimers (CPD) and pyrimidine(6-4)pyrimidone dimers ([6
      4]PD) in different tissues of Xiphophorus signum exposed to ultraviolet-B light.
      We found that the (6-4)PD was induced at 5 to 10-fold lower frequency than the
      CPD and that scalation provided considerable photoprotection against both
      photoproducts. Photoenzymatic repair (PER) was very efficient in X. signum with
      most of the lesions removed within 20 min; PER of CPD occurred at about twice the
      rate of (6-4)PD. Nucleotide excision repair (NER) was much less efficient than
      PER and the rates of CPD and (6-4)PD removal were comparable. PER was more
      efficient in the caudal fin compared to the lateral epidermis; the opposite was
      true for NER. Although the initial rate of CPD excision was five-fold faster in
      the lateral epidermis compared to the caudal fin a considerable amount of
      residual damage remained in both tissues. The diverse photochemical and
      photobiological responses observed in X. signum suggest that heritable traits
      governing deoxyribonucleic acid damage induction and repair may be involved in
      the susceptibility of other Xiphophorus species to melanomagenesis.

PMID- 10946582
TI  - Bioluminescence color determinants of Phrixothrix railroad-worm luciferases:
      chimeric luciferases, site-directed mutagenesis of Arg 215 and guanidine effect.
AB  - Chimeric proteins were produced using the green light-emitting luciferase of
      Phrixothrix vivianii (PxGr: lambda max = 548 nm) and the red light-emitting
      luciferase of Phrixothrix hirtus (PxRe: lambda max = 623 nm). Constructs
      containing residues 1-344 of the red light-emitting luciferase with residues 345
      545 of the green light emitting one emitted red light (PxReGr; lambda max = 613
      nm), while the reverse emitted green light (PxGrRe; lambda max = 552 nm). From
      these results we conclude that the region 1-344 determines the color of
      bioluminescence (BL) in railroad-worm luciferases, and that residues above 344
      are not involved. The substitution R215S in the green light-emitting luciferase
      (PxGr) resulted in a approximately 40 nm redshift on the BL spectrum (lambda max
      = 585 nm) and an associated decrease of activity, whereas the same mutation in
      PxRe luciferase had little effect. Guanidine was shown to cause blueshifts in the
      BL spectra and stimulate the activity of the red-emitting luciferases (from
      lambda max = 623 to lambda max = 600 nm) and in PxGr R215S (from lambda max = 585
      to lambda max = 560 nm) mutant luciferase, but not in the green-emitting
      luciferases, suggesting that guanidine can simulate positively charged residues
      involved in BL color determination.

PMID- 10946583
TI  - Covert face recognition in neurologically intact participants.
AB  - Prosopagnosic patients may maintain some ability to recognize familiar faces,
      although they remain unaware of this ability. This phenomenon--called covert face
      recognition--was investigated in neurologically intact participants, using
      priming techniques. Participants were quicker to indicate that a target-name was
      familiar when the preceding prime-face belonged to the same person compared with
      an unrelated familiar person. This was observed both when prime-faces could be
      recognized overtly and when they were presented too briefly to be recognized
      overtly (Exps. 1 and 2). Thus, covert face recognition was observed in
      neurologically intact participants. In Exp. 3, participants were quicker to
      recognize a familiar face when that person's face had been seen previously, but
      only when it had been recognized overtly on the first encounter. These results
      are interpreted within the framework of an interactive activation model of face
      recognition.

PMID- 10946584
TI  - The knowledge acquired during artificial grammar learning: testing the
      predictions of two connectionist models.
AB  - An artificial grammar learning experiment is reported which investigated whether
      three types of information are learned during this kind of task: information
      about the positions of single letters, about fragments of training strings, and
      about entire training strings. Results indicate that participants primarily
      learned information about string fragments and, to a lesser extent, information
      about positions of letters. Two connectionist models, an autoassociator and a
      simple recurrent network (SRN), were tested on their ability to account for these
      results. In the autoassociator simulations, similarity of test items to entire
      training items had a large effect, which was at variance with the experimental
      results. The results of the SRN simulations almost perfectly matched the
      experimental ones.

PMID- 10946585
TI  - Compensation for subliminal timing perturbations in perceptual-motor
      synchronization.
AB  - It is sometimes assumed that limits of temporal discrimination established in
      psychophysical tasks constrain the timing information available for the control
      of action. Results from the five perceptual-motor synchronization experiments
      presented here argue against this assumption. Experiment 1 demonstrates that
      subliminal (0.8-2%) local changes in interval duration in an otherwise
      isochronous auditory sequence are rapidly compensated for in the timing of
      synchronized finger tapping. If this compensation is based on perception of the
      highly variable synchronization error (SE) rather than of the local change in
      stimulus period, then it could be based solely on SEs that exceed the temporal
      order threshold. However, that hypothesis is ruled out by additional analyses of
      Exp. 1 and the results of Exp. 2, a combined synchronization and temporal order
      judgment task. Experiments 3-5 further show that three factors that affect the
      detectability of local deviations from stimulus isochrony do not inhibit
      effective compensation for such deviations in synchronized tapping. Experiment 5,
      a combined synchronization and detection task, shows directly that compensation
      for timing perturbations does not depend on explicit detection. Overall, the
      results suggest that the automatic processes involved in the temporal control of
      action have access to more accurate timing information than do the conscious
      decision processes of auditory temporal judgment.

PMID- 10946586
TI  - Response strategies and the Simon effect.
AB  - The study investigated whether the Simon effect, and its facilitation and
      interference components, shows up in reaction time (RT) or in movement time (MT),
      depending on the response strategy. Experiment 1 replicated a study by Hietanen
      and Rama. Subjects had to press one of two lateralised keys in response to one of
      two stimuli. The stimuli were presented in the center (neutral condition) or to
      the left or right side (corresponding or non-corresponding conditions). To press
      the response key, a reaching movement was necessary, and both RT and MT were
      recorded. One group of subjects showed an RT facilitation effect and an MT
      interference effect. Another group of subjects showed both MT facilitation and MT
      interference effects. It was hypothesized that the two groups used different
      response strategies. In Exps. 2 and 3, the subjects were explicitly instructed to
      use the two strategies that were hypothesized for Exp. 1. The results showed that
      whether facilitation and interference manifest themselves in RT or MT depends on
      the response strategy adopted by the subjects.

PMID- 10946587
TI  - Timing precision in continuation and synchronization tapping.
AB  - Wing and Kristofferson (1973) have shown that temporal precision in self-paced
      tapping is limited by variability in a central timekeeper and by variability
      arising in the peripheral motor system. Here we test an extension of the Wing
      Kristofferson model to synchronization with periodic external events that was
      proposed by Vorberg and Wing (1994). In addition to the timekeeper and motor
      components, a linear phase correction mechanism is assumed which is triggered by
      the last or the last two synchronization errors. The model is tested in an
      experiment that contrasts synchronized and self-paced trapping, with response
      periods ranging from 200-640 ms. The variances of timekeeper and motor delays and
      the error correction parameters were estimated from the auto-covariance functions
      of the inter-response intervals in continuation and the asynchronies in
      synchronization. Plausible estimates for all parameters were obtained when equal
      motor variance was assumed for synchronization and continuation. Timekeeper
      variance increased with metronome period, but more steeply during continuation
      than during synchronization, suggesting that internal timekeeping processes are
      stabilized by periodic external signals. First-order error correction became more
      important as the metronome period increased, whereas the contribution of second
      order error correction decreased. It is concluded that the extended two-level
      model accounts well for both synchronization and continuation performance.

PMID- 10946588
TI  - Auditory stimulus-response compatibility: is there a contribution of stimulus
      hand correspondence?
AB  - Simon, Hinrichs, and Craft found that when subjects responded to a tone in the
      left or right ear with a left or right keypress, both ear-response-location
      correspondence and ear-hand correspondence affected reaction time. This outcome
      is in contrast to results obtained for auditory and visual Simon tasks (i.e.,
      tasks in which stimulus location is irrelevant) as well as results obtained in
      visual stimulus-response (S-R) compatibility studies, which show only an effect
      of spatial S-R correspondence. Experiment 1 was a replication of Simon et al.'s
      experiment in which spatial mapping and hand placement (uncrossed, crossed) were
      varied. The results were inconsistent with those of Simon et al., showing no ear
      hand compatibility effect. Experiment 2 was a second replication with an
      additional condition examined in which the stimuli were visual locations. The
      results showed no contribution of stimulus-hand correspondence for either
      auditory or visual stimuli. Experiment 3 was a replication of another experiment
      by Simon et al. in which tone pitch was relevant and tone location irrelevant.
      Like Simon et al.'s data, our results showed no indication that stimulus-hand
      correspondence is a significant factor. Overall, our results imply that
      regardless of whether tone location is relevant or irrelevant, ear-response
      location correspondence is the only factor that contributes to S-R compatibility
      in auditory two-choice reaction tasks.

PMID- 10946589
TI  - Neighborhood-frequency effects when primes and targets are of different lengths.
AB  - The present study provides a further investigation of the neighborhood-frequency
      effect. Using the masked priming procedure, we found that the neighborhood
      frequency effect is obtained not only with primes and targets of the same length
      but also with primes and targets of a different length. This result is not
      compatible with most current versions of the interactive activation model.
      Implications of the finding are discussed.

PMID- 10946590
TI  - A redintegration account of the effects of speech rate, lexicality, and word
      frequency in immediate serial recall.
AB  - Short-term serial recall performance is strongly affected by the nature of the
      items to be remembered. For example, memory span declines with decreasing speech
      rate (i.e., increasing pronunciation duration) of the items and, for a given
      speech rate, memory for non-words is poorer than for words. Similarly, words of
      high natural language frequency are recalled better than low-frequency words.
      Existing descriptive models have identified redintegration as underlying many of
      those effects. Redintegration refers to the process by which partially retrieved
      memorial information is converted into an overt response. This article presents a
      process model of redintegration based on a non-linear dynamic network, which is
      shown to handle the effects of speech rate, lexicality, and word frequency on
      memory span. Unlike previous descriptive efforts, the redintegration model also
      predicts the shape of the underlying serial position curves.

PMID- 10946591
TI  - Model complexity: the fit to random data reconsidered.
AB  - A recent controversy in the field of depth perception has highlighted an
      important aspect of model testing concerning a model's complexity, defined as the
      prior propensity of the model to fit arbitrary data sets. The present article
      introduces an index of complexity, called the mean minimum distance, defined as
      the average squared distance between an arbitrary data point and the prediction
      range of the model. It may also be expressed as a dimensionless quantity called
      the scaled mean minimum distance. For linear models, theoretical values for the
      scaled mean minimum distance and the variance of the scaled minimum distance can
      be readily obtained and compared against empirical estimates obtained from fits
      to random data. The approach is applied to resolving the question of the relative
      complexity of the Linear Integration model and the Fuzzy Logic of Perception
      model, both of which have been the subject of controversy in the field of depth
      perception. It is concluded that the two models are equally complex.

PMID- 10946592
TI  - The Ornstein-Uhlenbeck model for decision time in cognitive tasks: an example of
      control of nonlinear network dynamics.
AB  - The Ornstein-Uhlenbeck (OU) model for human decision-making has been successfully
      applied to account for response accuracy and response time (RT) data in recent
      two-choice decision models. A variant of the OU model is shown to arise from the
      response dynamics of a nonlinear network consisting of randomly connected neural
      processing units. When feedback control of the network is effected by the
      stimulus onset, the average network response is an autocorrelated random signal
      satisfying the stochastic differential equation for the OU process. An
      alternative, more general, stimulus detection procedure is proposed which
      involves the use of an adaptive Kalman filter process to track any temporal
      change in autoregressive parameters. The predicted decision time distributions
      suggest that both the OU and the Kalman filter processes can serve as alternative
      models for RT data in experimental tasks.

PMID- 10946593
TI  - Direct estimates of processing delays in the attentional blink.
AB  - When two targets (T1 and T2) are presented in rapid succession, identification of
      T2 is often impaired (attentional blink: AB). The two-stage model accounts for
      the AB deficit by assuming that: (a) T2 is delayed in Stage 1 while Stage 2 is
      busy processing T1, and (b) T2 is vulnerable to masking while delayed. We report
      converging evidence for the model by evaluating these assumptions independently
      of the AB deficit itself. The results show that: (a) response times for T2
      identification decreased as the lag between T1 and T2 was increased; (b) response
      times for T2 decreased across lags only if T1 was masked; and (c) accuracy of T2
      identification increased as the stimulus-onset asynchrony between T2 and the
      trailing mask was increased.

PMID- 10946594
TI  - Is judgment of random time intervals biased and capacity-limited?
AB  - Recently, random generation of time intervals has been proposed as a procedure to
      impair executive processing in a dual-task paradigm without substantial
      interference with phonological and visuo-spatial working memory resources. A
      fundamental assumption of this procedure is that humans are able to distinguish
      time sequences on their degree of randomness. The present study tests this
      assumption. To this end, non-biased, repetition-biased, alternation-biased
      sequences and repetitive rhythms were judged under conditions of higher or lower
      executive load. In Exp. 1, load depended on the presentation speed, while in Exp.
      2, a dual-task condition was used with either a concurrent number-copying task or
      an arithmetic task. It was found that the participants could distinguish
      repetitive rhythms from more or less random sequences, and that both accuracy of
      this judgment and latency were affected by the concurrent load. The findings are
      taken as a first indication that random time judgment is capacity-limited.

PMID- 10946595
TI  - Progress towards poliomyelitis eradication, WHO European Region, June 1998-June
      2000.

PMID- 10946596
TI  - Intervention research on onchocerciasis and lymphatic filariasis.

PMID- 10946598
TI  - [The diagnosis and operative treatment of solitary thyroid nodule: a prospective
      study].
AB  - The aim of the paper is to evaluate the usefulness of pre- and intraoperative
      examination methods in the diagnostics of solitary thyroid nodules, as well as
      the assessment of the histologic structure of these nodules. From 1.12.1997 to
      15.06.1998 in the Clinic of Endocrinological and General Surgery at the Medical
      University of Lodz, 102 patients were operated for a solitary nodule. The
      solitary nodule was diagnosed on the basis of the clinical and ultrasound
      examination. A fine needle aspiration biopsy (FNAB) was performed in all
      patients. During the operation the presence of the solitary nodule was confirmed
      on the basis of macroscopic examination. If malignancy was suspected on
      intraoperative macroscopic examination, intraoperative histologic examination was
      carried out. In 82 patients with the solitary nodule, the benign nodule was
      diagnosed on the basis of FNAB in 45 (54.9%) patients and malignant one in 8
      (9.7%). Malignancy in the nodule (follicular tumour, Hurthle cell tumour,
      cellulae suspectae) was suspected in 29 (35.4%) patients--in this group the
      intraoperative histologic examination was conducted. On the basis of
      postoperative histologic examination a thyroid malignant neoplasm was detected in
      18 (21.9%) of 82 patients with the solitary nodule. Finally, out of 18 thyroid
      cancers, 8 (44.4%) were recognised preoperatively (FNAB), 3 (16.7%)
      intraoperatively and 7 postoperatively. Since the incidence of malignancy in
      solitary thyroid nodules is high the authors suggest that their precise pre- and
      intraoperative diagnostics is necessary. The use of described diagnostic methods
      enabled to recognise malignancy in the solitary nodule and to perform a primary
      radical operation in 61.1% patients. On the basis of the obtained results it
      seems justifiable to search new diagnostic methods which enable better pre- and
      intraoperative differentiation of benign and malignant thyroid nodules.

PMID- 10946597
TI  - [Dynamics of the course of neoplastic disease and status of antioxidant system].
AB  - The decreased ability to remove free radicals from organism is one of the factors
      which furthers the development of neoplastic process. Enzymes and substrates
      which can remove free radicals from organism from antioxidant barrier. The
      appreciation of some elements of antioxidant organism barrier in children with
      neoplastic disease was the study's purpose. We examined 100 children in the age
      from 6 months to 16 years (60 patients with malignant solid tumors and 40 healthy
      children as a control group). We investigated glutathione peroxidase, catalase
      and superoxide dismutase activities in erythrocytes. In these children we studied
      also catalase activity, ceruloplasmin concentration and antioxidant barrier level
      in plasma. We estimated antioxidant elements in patients with cancer before,
      during and after treatment and during remission and progression of the disease.
      The decrease of total antioxidant barrier was typical in introductory period of
      neoplastic disease. We observed the increase of superoxide dismutase and
      glutathione peroxidase in erythrocytes and catalase activity in plasma in
      children with clinical remission but we found the gradual decrease of
      ceruloplasmin level in plasma.

PMID- 10946599
TI  - [Esophageal substitute corrective operations].
AB  - In the Clinic of Gastrointestinal Surgery at the Medical University in Wroclaw in
      402 cases substernal oesophageal reconstruction was performed using different
      pedunculated oesophageal substitutes. 63 patients had to be operated on for the
      second time because of disorders in the oesophageal substitute. In 13 cases
      stenosis in the upper anastomosis and in 3 patients stenosis in the anastomosis
      with stomach were corrected. In 7 cases oesophageal ulcer was excised. 6 patients
      were operated because of substitute herniation into pleural cavity. In 3 cases
      huge diverticula in the neck were removed. 5 patients were operated because of
      stomach outlet stenosis. In 15 cases operation was necessary to correct the
      sequel of reflux oesophagitis. In 8 cases the surgery was performed to remove
      stenosis of the substitute. In 2 cases there was torsion of substitute and in the
      other 2 cases postoperative stenosis was caused by adhesions. One patient was
      operated because of the dumping syndrome. In 2 patients with the colon substitute
      polyps from the segment used for the oesophagus were removed endoscopically. The
      mortality after corrective surgery on the oesophageal substitute was less than
      10% (6/63).

PMID- 10946600
TI  - [Influence of some infusion fluids on red blood cells deformity in vitro].
AB  - The aim of this study was in vitro investigation of the influence of following
      infusion liquids: 20% human albumin, 5% dextran 40,000, 10% hydroxyethylstarch,
      0.9% NaCl and Ringer lactate solution on red cell blood corpuscles deformability
      (elongation index). Examinations were compared with erythrocytes suspended in
      autologous plasma. Infusion liquids were added to red blood cells suspension and
      incubated during 30 minutes at 37 degrees C. The erythrocyte deformability was
      measured by shear stress defractometer Rheodyn SSD. We observed the slight
      increase of erythrocyte deformability under the influence of hydroxyethylstarch
      and lactate buffered Ringer solution.

PMID- 10946601
TI  - [Carbon monoxide poisoning in children hospitalized in the pediatric institute in
      Lodz in the years 1994-1997].
AB  - Carbon monoxide poisoning is the major cause of inhalation intoxications among
      children. Tissue hypoxia plays the important role in the pathophysiology of CO
      poisoning. Especially the CNS and heart are the most susceptible organs to the
      oxygen deficiency. Presented signs and symptoms are nonspecific and often lead to
      misdiagnosis. In this article authors present 100 children, aged from 4 weeks to
      15 years, hospitalized in the Pediatrics Institute in the period 1994-1997 after
      carbon monoxide exposition. The most frequent symptoms of this poisoning were
      headache (46%) and dizziness (25%). We also observed abdominal pain, vomitus,
      fatigue, weakness and syncope. We estimated the frequency of CO poisoning in
      relation to the total number of intoxications in children treated in our
      hospital, clinical course and relationship with carboxyhemoglobin concentration.
      The analysis shows that CO poisoning is an important and growing toxicological
      problem among children.

PMID- 10946602
TI  - [Manometric examinations in esophageal peristalsis disorders].
AB  - Many centers besides radiography and endoscopy, perform manometric measurements
      in the diagnostics of diseases concerning esophagus and cardia. They which allow
      to determine esophageal body peristalsis, LES length with spatial distribution of
      pressures (Vector Volume). The aim of our study was the estimation of usefulness
      the esophageal and cardial computed manometry in disorders concerning motor
      activity of the upper part of gastrointestinal tract. In our hospital between
      March 1997 and March 1998 we examined 12 patients with cardial achalasia, 9
      patients with hiatal hernia, 2 ones with features of gastroesophageal reflux
      without hernia and 1 patient with diffuse esophageal spasm. All patients were
      examined preoperatively, on the 7th postoperative day and postoperatively--after
      a month. Computer recording of pressures was made. In postoperative examination
      we revealed favourable improvement in gastroesophageal passage with marked
      decrease of LES pressures in patients after dilation. However in patients after
      Nissen's operation LES pressures exceeded upper normal range on the 7th day
      postoperatively, but they came back to normal range within a month after
      operation.

PMID- 10946604
TI  - [Neurovascular compression within posterior cranial cavity].
AB  - 30 years ago Janetta proposed neurovascular compression as an etiology factor of
      trigeminal neuralgia. Neuroanatomical, neurophysiological studies and
      observations during neurosurgical operations seems to confirm Janetta's
      suggestions. The conception of neurovascular compression was accepted also as an
      etiology factor in hemifacial spasm. There are more diseases of unknown etiology
      described in literature in which neurovascular compression as an etiological
      factor is suspected. The results of initial treatment of these diseases performed
      by neurovascular decompression were presented. We are described the methods of
      contemporary diagnostics of neurovascular compression syndrome. The difficulties
      with correct diagnostics were underlined. MRI and neurophysiological examinations
      were pointed out as the most useful in an evaluation of neurovascular compression
      syndromes.

PMID- 10946603
TI  - [The effect of 6 week treatment with theophylline on spirometric parameters,
      nonspecific bronchial reactivity and the concentration of soluble interleukin 2
      receptor in serum of asthmatic patients].
AB  - This study allowed to investigate the effect of theophylline (Theo-Dur Astra)
      given 1 tablet a 200 mg per day in the evening for six weeks on histamine-induced
      airways responsiveness++ (PC20H), spirometric parameters and the concentration of
      soluble interleukin 2 receptor (sIL-2R) in serum. 21 patients with mild asthma (6
      women, 15 men), average age 34.8 +/- 11.4 years were qualified for this study.
      PC20H was estimated according to Cockroft's method using pneumatic inhalator
      (Voyage-Secura Nova). Concentration of sIL-2R in serum was measured by Predicta
      Interleukin 2 Receptor Kit (Genzyme). Lung function test was measured by means of
      ABC PNEUMO (abc MED). Six week treatment with theophylline significantly
      increased PC20H in comparison with basal results (0.74 +/- 0.68 mg/ml before and
      0.89 +/- 0.71 mg/ml after p < 0.04). The concentration of sIL-2R in serum did not
      change significantly during theophylline therapy. Treatment with theophylline
      significantly increased FEV1 (3.64 l/sec before and 3.84 l/sec after p < 0.001).
      The anti-inflammatory effect of theophilline is more clearly shown in the
      decrease of histamine-inducted airways responsiveness than in the decreased
      concentration of sIL-2R in serum.

PMID- 10946605
TI  - [Mosquito bites hypersensitivity: clinical and therapeutic approach].
AB  - Hypersensitivity to mosquito bites is an underestimated clinical and
      therapeutical problem. When feeding, female mosquitoes inject saliva, containing
      antigens and potentially toxic substances, into the human skin. The cutaneous
      response to mosquito bites is expressed as pruritus and oedema. The systemic
      symptoms are observed rarely. Nevertheless, the symptoms caused by mosquito bites
      are troublesome. In this paper clinical picture of mosquito bites consequences
      and up-to-date conceptions pathomechanism relating to their are shown. Moreover,
      prophylactic and therapeutical approaches are presented.

PMID- 10946606
TI  - [Multi-site pace making for dilated cardiomyopathy].
AB  - Dual chamber pacing (DDD) has been reported to be effective in patients with
      dilated cardiomyopathy (DCM). Other works, however, show contradictory results.
      Deleterious effects resulting from desynchronization of the right and left
      ventricular contraction have been suggested. In patients with end-stage DCM and
      severe congestive heart failure multisite pacing may be associated with fast and
      sustained hemodynamic improvement.

PMID- 10946607
TI  - [Monosymptomatic nocturnal enuresis: disease or complaint?].
AB  - Nocturnal enuresis is an innocent but distressing disorder occurring in many
      children. It can negatively affect early childhood and can last until adulthood.
      This may result in emotional stress behavioural problems and poor self-esteem.
      Physicians should realize that nocturnal enuresis can be an important problem not
      only for the child but also for the entire family, although it is known that
      enuresis frequently stops spontaneously.

PMID- 10946608
TI  - [Examination of the pleural effusion and its interpretation].
AB  - Pleural effusion appears in the course of respiratory diseases and disorders of
      other organs. Examination of the effusion enables differentiation between exudate
      or transudate. It allows to estimate the severity of the disease, helps to choose
      the way of treatment and assesses its effects. In most cases Light's criteria are
      sufficient for differentiation between exudate and transudate. If the patient has
      an exudative pleural effusion additional tests are indicated to determine the
      etiology of the effusion. Laboratory tests which are useful in the further
      diagnostics of pleural effusion include: bacterial cultures, cytological and
      biochemical tests.

PMID- 10946609
TI  - [Ischemic preconditioning: a new issue in cardiology. Part I: preliminary
      studies: a suggested mechanism of the phenomenon].
AB  - The aim of this paper is the presentation of scientific experiments dedicated to
      understanding the mechanisms of ischemic preconditioning. The information about
      numerous cellular receptors involved in this process is reported. Other elements,
      mediating in the cascade of biochemical changes leading to the increase in
      resistance of the heart to ischemia are also described.

PMID- 10946610
TI  - [Primary gastric non-Hodgkin lymphoma].
AB  - Authors discussed etiology, diagnostic and therapeutical problems in the
      treatment of primary gastric non-Hodgkin lymphoma. The first one was limited to
      the gastric region and was cured favourably. The second one extended gastric
      region and affected all alimentary tract. This case was terminated by death of
      the patient.

PMID- 10946611
TI  - [Malignant external otitis: a rare complication after autologous bone marrow
      transplantation].
AB  - We present a case of 39 year old woman who developed malignant external otitis
      (m.e.o.) of Pseudomonas aeruginosa aetiology during pancytopenia after autologous
      bone marrow transplantation (ABMT). The infection was probably of endogenous
      origin. 7 days before ABMT otolarygological examination including otoscopy and
      external ear lavage was performed. Slight inflammatory reaction of external ear
      was accompanied by the massive involvement of middle ear followed by infiltration
      of petrous pyramid and mastoid process and finally facial and vestibulocochlear
      nerve paralysis. Initially the symptoms indicated subarachnoid haemorrhage.
      Mononuclear cells detected in cerebrospinal fluid as well as CT scan were
      suggestive of leukaemic infiltration. The latter was negated by immunophenotyping
      of cerebrospinal fluid cells and MR imaging. Antibiotic therapy resulted in
      clinical improvement. Life-threatening complications are not frequent after ABMT
      (transplant related mortality--14/310 (4.5%) in our center). We have met m.e.o.
      for the first time. At present--13 months after ABMT the patient shows slight
      symptoms of nerve VII and VIII paresis and remains in complete remission of acute
      leukaemia. We emphasize the importance of proper preparation of patients for high
      dose chemotherapy followed by bone marrow transplantation as well as diagnostic
      difficulties related to pancytopenia.

PMID- 10946612
TI  - [Laparoscopic excision of huge spleen in a 5-year-old boy with hypersplenism].
AB  - Minimally invasive surgery has been recently gaining acceptance as an alternative
      to "open" surgery. The benefits of video-surgery consist of minor surgical trauma
      of tissues, shorter hospital stay, quicker return to full activity and better
      cosmetic effect compared to traditional splenectomy. Less peritoneal adhesions
      after laparoscopic splenectomy decreases also the risk of strangulation ileus in
      the future. Authors present laparoscopic splenectomy in 5 year-old boy with
      hypersplenism. Technical details, intraoperative difficulties, immediate and late
      outcome were described. The early results, advantages and disadvantages were also
      discussed.

PMID- 10946613
TI  - [Long term results after surgical treatment of hepatolithiasis].
AB  - The paper presents a case of hepatolithiasis. Final diagnosis was established due
      to computed tomography and endoscopic recurrent cholangiopancreatography many
      years after the first symptoms' occurrence. Left hemihepatectomy was performed
      with very good 5-year result.

PMID- 10946614
TI  - [The coexistence of breast and ovarian cancer in patient with insertion
      duplication of 12bp in BRCA1 gene].
AB  - In the paper we present the case of 39-year old patient admitted to the hospital
      because of double cancer (i.e. breast and ovarian cancer). This coexistence made
      us to check with PCR the possible irregularity in BCRA1 gene structure. The
      result of the study was the finding of insertion-duplication 12 bp in BRCA1 gene.

PMID- 10946615
TI  - [Identification and characterization of hexokinase isozyme predominantly
      expressed in malignant tumor cells].
AB  - Tumor cells show a higher glycolytic rate than normal cells. Of glycolytic
      enzymes, the activity of hexokinase, known as a rate limiting enzyme in
      glycolysis, is amazingly high in malignant tumor cells. In mammals, four isozymes
      of hexokinase are expressed but the question which isozyme is responsible for the
      high hexokinase activity observed in tumor cells was not yet clearly answered. By
      Northern blot analysis, we found that the type II isozyme, which is only slightly
      expressed in normal heart, muscle and adipose tissue, was remarkably expressed in
      malignant tumor cells. We next tried to understand how the expression of type II
      hexokinase gene is regulated in tumor cells. For this purpose, we first isolated
      the type II hexokinase gene and characterized its structural features. We further
      investigated the regulatory mechanisms of the expression of type II hexokinase in
      tumor cells. Results indicate the potential involvement of a serum responsive
      factor in the regulation of the expression of type II hexokinase in tumor cells.
      In addition to the remarkable expression, binding of the type II hexokinase to
      mitochondria is another characteristic of tumor cells, however, the physiological
      meaning of hexokinase binding to mitochondria was not yet fully understood. Our
      results clearly showed that the mitochondria-bound hexokinase utilize
      mitochondrially generated ATP more preferentially under normal conditions.
      However, when the rate of extramitochondrial ATP generating system (glycolysis)
      exceed that of mitochondrial ATP generating system (oxidative phosphorylation),
      the mitochondria-bound hexokinase utilize extramitochondrial ATP. This result
      indicates that the hexokinase binding enables a cross talk between oxidative
      phosphorylation and glycolysis.

PMID- 10946616
TI  - [Development of solid-phase radical reactions using oxime ethers as a radical
      acceptor].
AB  - Triethylborane has the potential to induce radical reactions on solid support and
      the solid-phase radical reactions were achieved by using triethylborane as a
      radical initiator. The intermolecular carbon radical addition to glyoxylic oxime
      ether anchored to Wang resin proceeded under very mild conditions to give alpha
      amino acid derivatives in good yield without interference of the polystyrene
      skeleton of the resin. Diethylzinc also worked well as a radical initiator at low
      reaction temperature. Thus, the employment of triethylborane or diethylzinc at
      low reaction temperature facilitated the control of stereochemistry in solid
      phase reactions. Alkyl radical addition to Oppolzer's camphorsultam derivatives
      of oxime ether anchored to a polymer support proceeded smoothly even at -78
      degrees C to give the alpha-amino acid derivatives with excellent
      diastereoselectivities. The radical cyclization of oxime the ethers anchored to a
      polymer support also proceeded effectively to provide functionalized pyrrolidines
      via a carbon-carbon bond-forming process.

PMID- 10946617
TI  - [Neuropsychopharmacological study on an animal model for negative symptom of
      schizophrenia induced by repeated phencyclidine treatment].
AB  - To develop an animal model for negative symptoms, in particular avolition, of
      schizophrenia, the effect of phencyclidine (PCP) on immobility (regarded as
      avolition) in the forced swimming test was investigated in mice, since PCP
      produces negative symptoms in humans. Unlike single, repeated treatment with PCP
      prolonged the immobility time in the forced swimming test 24 h after the final
      injection compared with saline treatment. The enhancing effect of PCP on the
      immobility persisted for 21 d after the withdrawal of the drug. Atypical
      antipsychotics attenuated the enhancing effect of PCP on the immobility. Since
      these attenuating effects were antagonized by a serotonin-S2 receptor agonist,
      (+/-)-2,5-dimethoxy-4-iodamphetamine (DOI), the effects may be mediated via
      serotonin-S2 receptors. In contrast with atypical antipsychotics, typical
      antipsychotics, antidepressants and anxiolytics had no effect. No functional
      changes in post-synaptic serotonin-S2 receptors were observed in PCP-treated mice
      following the forced swimming test. Serotonin utilization in the prefrontal
      cortex was increased, but dopamine utilization was decreased in PCP-treated mice
      showing the enhancement of immobility. The enhancing effect of PCP was
      significantly attenuated by D-cycloserine, an agonist for glycine binding site of
      N-methyl-D-aspartate (NMDA) receptor ionophore complex. Decreases of NMDA
      receptor function or of the cortical glutamate and glycine levels were observed
      in PCP-treated mice showing the enhancement of immobility. These results suggest
      that the enhancing effect of PCP on immobility is mediated by the imbalance of
      the cortical serotonergic, dopaminergic and glutamatergic systems and could be
      used as an animal model for negative symptoms of schizophrenia.

PMID- 10946618
TI  - [New therapy reduces AIDS passed to fetuses and costs less].
AB  - The AIDS clinical group protocol of zidovudine (AZT) prophylaxis regimen for HIV
      1-infected pregnant women and their babies has been associated with a decrease in
      vertical HIV-1 transmission in non-breastfeeding women in developmental
      countries. However, scientists furthermore compared the safety and efficacy of
      short-course nevirapine or AZT during labour and the first week of life. In an
      advancement that promises to significantly reduce the incidence of AIDS in
      children in developing countries, scientists have found a simple new way with
      nevirapine to prevent mother-to-child transmission of the AIDS virus that also is
      less costly and markedly more effective than the standard therapy with AZT in the
      third world. The more practical therapy comes from substituting one marketed
      drug, nevirapine, for the standard drug, AZT. The cost for the two doses of
      nevirapine was $4, compared with $268 for AZT regimen now used in developing
      countries and $815 for the much longer and more complicated course used in the
      U.S. and other developing countries. It is proposed that wide-scale use of
      nevirapine in developing countries could potentially prevent 300,000 to 400,000
      newborns each year from beginning life infected with HIV.

PMID- 10946619
TI  - [Development and evaluation of an individuals-oriented information-provision
      system for outpatients--utility of "drug Usage sheets" and "Drug Information
      Cards" for patient consultation].
AB  - We have implemented an information-provision system for outpatients at the
      department of pharmacy, University of Tokyo Hospital, in order to comply with the
      revised Pharmacists' Law by which pharmacists have been obliged to provide
      patients with information necessary for rational usage of medicine at the time
      they receive dispensed drugs. This system is linked on-line with the order entry
      system to print "Drug Usage Sheets" containing important drug information such as
      therapeutic effects and adverse reactions, as well as photographic color views of
      drugs. We prepared the sheets by extracting and classifying the original
      information, and by converting medical terms into lay expressions. Moreover, we
      developed "Drug Information Cards" to inform each patient of severe side effects
      and drug interactions, which should affect drug compliance, and implemented an
      individuals-oriented information system using both the "Drug Usage Sheets" and
      "Drug Information Cards." In this study, we evaluated the usefulness of this
      system from the viewpoint of patients' recognition and understanding on necessary
      drug information. It was indicated from questionnaires to patients that the "Drug
      Usage Sheets" help most patients understand the names, usage, effects, and
      general cautions including slight adverse reactions (i.e. grade 1), and that the
      use of colored letters for important parts and pictograms is a useful method to
      attract more attention from patients as compared with a conventional method using
      only letters. Most patients answered that the "Drug Usage Sheets" can be utilized
      in many ways and valuable in taking drugs with assurance. We formulated the "Drug
      Information Cards" by information processing: separation of early symptoms of
      adverse effects into subjective and objective ones and their classification into
      related organs. Moreover, the brand names of drugs which may cause drug
      interactions have been listed on the cards so that worsening of adverse reactions
      and drug interactions can be avoided. Although 14% of the patients answered that
      they became unsecured when informed on side effects, the percentage of such
      patients was significantly higher with those who received caution-required drugs
      for the first time or who have experienced drug side effects before, suggesting
      the need for combining oral explanation based on each patient's background and
      understanding on drug adverse effects. In conclusion, an efficient provision of
      drug information became possible through our integration of necessary drug
      information in this study, and the individuals-oriented system of drug
      information was established, which was demonstrated to contribute to the rational
      usage of medicine.

PMID- 10946620
TI  - [Estimation of adverse drug reactions by the evaluation scores of subjective
      symptoms (complaints) and background of patients. V. Drug-induced
      gastrointestinal system disorders].
AB  - OBJECTIVES: The purpose of this study was to develop, implement, and assess an
      estimation procedure for preventing adverse drug reaction by subjective symptoms
      (complaints) of patients. This time, we focused and studied on drug-induced
      gastrointestinal system disorders. METHODS: We have built a database for CARPIS
      (Case Reports of Adverse Drug Reaction and Poisoning Information System) since
      1987. We studied 224 cases of drug-induced Gastrointestinal System Disorders
      (stomach or colon disorders: 148, esophagus disorders: 31, pancreas disorders:
      45) cumulated in the CARPIS database. The evaluation scores were created based on
      the subjective symptoms and backgrounds of the patients. We estimated 224 cases
      using these evaluation scores. RESULTS: We could estimate 137 cases (92.6%) in
      148 cases to be stomach or colon disorders by the use of these evaluation scores.
      The validity of this evaluation scores was estimated to be as follows:
      Sensitivity = 92.6%, Specificity = 95.0% and Predictive Value of Positive Test
      (PVP) = 96.5%. The positive likelihood ratio (LR) was 18.5 and negative
      likelihood ratio was 0.08. On the other hand, in the case of esophagus disorders,
      PVP was 84.8% and LR was 18.1. In the case of pancreas disorders, PVP was 90.7%
      and LR was 21.7. CONCLUSIONS: In this study, PVP and LR values were good. We
      thought that these evaluation scores could pick up the drug-induced
      gastrointestinal system disorders efficiently. We reported previously the
      evaluation scores about drug-induced liver disorders, extra-pyramidal symptoms,
      leukopenia and eruption before. In order to apply these evaluation scores onto
      the clinical practice, we prepared an evaluation form for subjective symptoms and
      backgrounds of the patients with adverse drug reactions. As a result, the adverse
      reactions symptoms of each one defined more.

PMID- 10946687
TI  - Evaluation of lower extremity bypass grafts with use of color duplex sonography.
AB  - This article reviews the wide variety of graft procedures currently used to
      bypass lower extremity atherosclerotic disease and the means used to evaluate the
      grafts, which can be biologic, synthetic, or a combination of both. Graft failure
      rate can be as high as 10% within the first 10-14 days after placement, leveling
      off to approximately 2%-4% per year thereafter. Many of the early complications
      associated with graft placement can be attributed to technical errors in bypass
      construction. Although angiography remains the standard of reference for the
      evaluation of these grafts, duplex ultrasound is increasingly being utilized to
      document patency and detect suspected complications such as intimal flap,
      perigraft collection, arteriovenous fistula, pseudoaneurysm, and stenosis or
      occlusion. Sonography is able to clearly depict the echogenic walls of synthetic
      grafts and demonstrate whether blood flow wave-forms and blood flow velocity in
      both synthetic and biologic grafts are normal, thus enabling a more accurate
      diagnosis of suspected complications to be made. Familiarity with the normal
      sonographic appearance of these grafts, their anastomoses, potential
      complications, and the pitfalls in making a diagnosis is essential if an accurate
      diagnosis is to be made.

PMID- 10946621
TI  - [Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal
      opportunistic infections in mice].
AB  - The prophylactic effects of a Basidiomycetes preparation, AHCC, against
      experimental opportunistic infections were investigated in leukopenic mice. In
      cyclophosphamide-induced leukopenic mice, oral or intraperitoneal administration
      of the AHCC at doses of 1000 or 50 mg/kg/day, respectively, for 4 consecutive
      days prior to Candida albicans infection significantly prolonged the survival
      periods of the infected mice, and decreased the viable counts of C. albicans
      cells recovered from their kidneys. Similarly, the oral treatment with AHCC
      protected mice from lethal infection with Pseudomonas aeruginosa and
      intraperitoneal one also protected mice from infection with methicillin-resistant
      Staphylococcus aureus (MRSA). These results suggest a potential usefulness of the
      AHCC as a prophylactic agent for the management of patients with opportunistic
      infections.

PMID- 10946688
TI  - Imaging of small airways disease.
AB  - High-resolution computed tomography (HRCT) is the most useful modality for
      imaging of small airways disease. Direct signs of small airways disease that
      appear on HRCT scans are the result of changes in the airway wall or lumen.
      Abnormal small airways can be seen as tubular, nodular, or branching linear
      structures on HRCT scans. Indirect signs of small airways disease result from
      changes in the lung parenchyma distal to the diseased small airway and include
      air trapping, subsegmental atelectasis, centrilobular emphysema, and air-space
      nodules. Diverse inflammatory and infectious processes, such as bronchiolitis
      obliterans (BO), bronchiolitis obliterans with organizing pneumonia (BOOP),
      smoking-related diseases, and asthma affect the small airways of the lungs. HRCT
      findings of BO include air trapping and bronchiectasis. The predominant findings
      of BOOP are consolidation and ground-glass attenuation. HRCT can show
      abnormalities such as small nodules and areas of ground-glass attenuation even in
      asymptomatic smokers, but emphysema predominates in smokers with moderate or
      severe obstructive disease. Patients with asthma can have thickened airway walls,
      plugged large and small airways, subsegmental atelectasis, and air trapping, but
      emphysema is rarely seen even in severe asthma patients. HRCT scans can often
      accurately depict disease processes in the small airways and can occasionally
      lead to a specific diagnosis from among several clinically relevant
      possibilities.

PMID- 10946689
TI  - Contributions of newer MR imaging strategies for congenital heart disease.
AB  - Magnetic resonance (MR) imaging is a valuable noninvasive adjunct in the
      evaluation of congenital heart disease (CHD). With its multiplanar image
      acquisition, good spatial resolution, and large-field-of-view image display, MR
      imaging can allow appreciation of vascular connections not readily apparent at
      echocardiography or angiography. Evaluation of CHD with MR imaging has two
      components: definition of cardiovascular anatomy and characterization of blood
      flow. However, the variety of MR imaging options is large and often confusing.
      Besides spin-echo and gradient-echo imaging, MR imaging techniques for evaluation
      of CHD include MR angiography, cine MR imaging, and flow quantification. An
      understanding of the potential MR imaging options enables formulation and more
      efficient application of MR imaging strategies. When performed well, MR imaging
      greatly enhances surgical planning and can even obviate cardiac catheterization.
      MR imaging is also an excellent modality for serial evaluation of surgical
      results and complications in cases of CHD.

PMID- 10946690
TI  - Breast MR imaging for cancer detection and implant evaluation: potential
      pitfalls.
AB  - Magnetic resonance (MR) imaging of the breast is currently used for evaluation of
      both parenchymal disease and silicone gel implants. MR imaging has the potential
      to address questions raised or unanswered with traditional diagnostic imaging
      methods. However, lesion specificity and cancer sensitivity depend on multiple
      technical factors (i.e., imaging parameters and contrast agent delivery) and
      biologic factors (i.e., the menstrual status of the patient and the vascularity
      of the lesion). Although diagnostic criteria for parenchymal disease have been
      reported, overlap of malignant and benign enhancement profiles occurs. The
      accuracy of implant evaluation depends on the imaging parameters and knowledge of
      the implant type and surgical history. In addition, individual investigative
      imaging methods are diverse, causing difficulty in protocol development for the
      practicing radiologist. An awareness of the problematic factors in breast MR
      imaging will improve diagnostic accuracy and allow understanding of the
      limitations of the modality and individual patient examinations.

PMID- 10946691
TI  - MR myelography of the cervical spine.
AB  - In previous studies, magnetic resonance (MR) myelography was not effective in the
      cervical region. However, effective cervical MR myelography is possible with a
      modified fast spin-echo sequence (8,000/360 [repetition time msec/effective echo
      time msec], four signals averaged, echo train length of 24). In a clinical study
      of this protocol, MR myelography was performed as an additional sequence
      following conventional MR imaging; composite images were obtained with a maximum
      intensity projection algorithm. The MR myelographic sequence added only 8.5
      minutes to the total imaging time and yielded information not provided by MR
      imaging in 13% of patients. MR myelography was especially valuable in
      demonstrating abnormal intraspinal vascularity and in guiding patient treatment
      by providing detailed preoperative information about intradural masses and
      posttraumatic and postoperative diverticulum and meningocele. This MR
      myelographic technique is a useful adjunct to MR imaging, especially in cases in
      which the more detailed information provided will be helpful in the analysis of
      complex intraspinal disease.

PMID- 10946692
TI  - Percutaneous laser disk decompression under CT and fluoroscopic guidance:
      indications, technique, and clinical experience.
AB  - The aim of percutaneous laser disk decompression (PLDD) is to vaporize a small
      portion of the nucleus pulposus of an intervertebral disk, thereby reducing the
      volume and pressure of a diseased disk. This minimally invasive technique can be
      performed in patients who need surgical intervention for disk herniation with leg
      pain. PLDD is usually performed under fluoroscopic guidance with or without
      diskoscopy. However, it can also be performed under dual computed tomographic
      (CT) and fluoroscopic guidance as an outpatient procedure. CT and fluoroscopic
      guidance increases the safety and accuracy of PLDD, with high precision of
      instrument guidance, direct visualization of nucleus pulposus vaporization, and
      reduced risk of complications. Of 119 patients with lumbar disk herniation
      treated with PLDD under CT and fluoroscopic guidance, 91 (76.5%) had a good or
      fair response. PLDD performed with CT and fluoroscopic guidance appears to be a
      safe and effective treatment for herniated intervertebral disks.

PMID- 10946693
TI  - MR imaging interpretation of the Palmer classification of triangular
      fibrocartilage complex lesions.
AB  - The triangular fibrocartilage complex (TFCC) is a complex anatomic and
      biomechanical structure. Injury to the TFCC is a recognized cause of ulnar wrist
      pain. The TFCC may be injured in its horizontal portion, in its peripheral
      portions, or at its attachments. In the Palmer classification, TFCC lesions are
      categorized as traumatic or degenerative. Traumatic lesions are subclassified
      according to the location of the injury; degenerative lesions are subclassified
      according to the extent of degeneration. This classification is helpful in
      determining the mechanism of injury and directing clinical management. Magnetic
      resonance (MR) imaging may be more useful than arthrography in prospective
      evaluation of TFCC lesions. MR images accurately demonstrate the structural
      abnormalities that contribute to ulnocarpal instability and pain. The presence or
      absence of chondromalacia is a factor in the Palmer classification and is also
      considered in treatment planning. However, only advanced cases of chondromalacia
      are reliably detected with MR imaging.

PMID- 10946694
TI  - Cystic masses of the spleen: radiologic-pathologic correlation.
AB  - Many focal splenic lesions may appear to be cystic at cross-sectional imaging. In
      this article, the following types of cystic splenic masses are discussed:
      congenital (true cyst), inflammatory (abscesses, hydatid cyst), vascular
      (infarction, peliosis), posttraumatic (hematoma, false cyst), and neoplastic
      (hemangioma, lymphangioma, lymphoma, metastasis). The key findings at ultrasound,
      computed tomography, and magnetic resonance imaging can be correlated with
      underlying gross and microscopic pathologic findings. Although tissue sampling is
      still required in many cases to yield a definitive diagnosis, recognition and
      understanding of the spectrum of imaging and pathologic features of these lesions
      often help narrow the differential diagnosis.

PMID- 10946695
TI  - From the archives of the AFIP. Gestational trophoblastic disease: radiologic
      pathologic correlation.
AB  - Gestational trophoblastic disease (GTD) is a manifestation of an aberrant
      fertilization event that leads to a proliferative process and, potentially, to an
      invasive neoplasm. The spectrum of GTD includes hydatidiform moles (complete and
      partial), invasive mole, choriocarcinoma, and placental site trophoblastic
      disease (rare). Increased levels of human chorionic gonadotropin (beta-hCG) are
      associated with all forms. Ultrasonography (US), performed late in the first
      trimester of a pregnancy complicated by hyperemesis gravidarum, toxemia, or
      bleeding, is essential in the early detection of hydatidiform mole, the most
      common form of GTD (80% of cases). In these cases, US typically reveals a central
      heterogeneous mass with anechoic spaces, which correspond to hydropic villi. In
      cases of invasive mole, imaging may show a central uterine process (similar to
      that seen in noninvasive moles), occasionally with myometrial invasion.
      Choriocarcinoma is often seen as a mass enlarging the uterus, with a
      heterogeneity that correlates with necrosis and hemorrhage. Because of the
      widespread availability of serum measurement of beta-hCG, diagnosis of the more
      severe, persistent manifestations of GTD seldom depends on radiologic
      examinations. However, imaging studies may alert the referring physician to the
      diagnosis in cases of early disease. Also, imaging studies may have a problem
      solving role in examining patients with recurrent GTD or a confusing clinical
      picture.

PMID- 10946696
TI  - From the RSNA refresher courses. Freehand interventional sonography in the
      breast: basic principles and clinical applications.
AB  - The skills needed to perform ultrasonographic (US)-guided interventional
      procedures in the breast can be learned by practicing the key maneuvers on a
      tissue phantom. Use of a tissue phantom rather than a synthetic phantom provides
      the tactile feedback from transducer movement against tissue and from needle
      insertion into tissue, which more closely simulates the performance of the
      procedure in a real breast. There are three key transducer motions--sweeping,
      rocking, and rotating--that are used to achieve three important goals in US
      guided procedures: finding the needle, maximally visualizing the needle, and
      correctly aligning the needle shaft and ultrasound beam. For each transducer
      maneuver, there is a corollary needle motion that can be used to achieve the same
      goal. Either the transducer or the needle should be moved during a procedure, not
      both simultaneously. Longitudinal alignment of the needle shaft with the
      ultrasound beam is best achieved with the perpendicular approach. The
      perpendicular approach is preferred because it allows superior needle
      visualization, orientation parallel to the chest wall, and location of the needle
      shaft at the focal zone. With use of a tissue phantom, the radiologist-in
      training can practice the key procedures and tailor them to his or her individual
      preferences.

PMID- 10946697
TI  - Unobtrusive evaluation of mammographer's eye movements during diagnosis of
      mammograms.
AB  - The authors sought to evaluate the visual search patterns of mammographers to
      better understand the process by which a diagnosis is reached when mammographic
      images are viewed. An unobtrusive gaze tracking system was applied to track gaze
      direction and pupil size. Data were collected at 60 Hz and analyzed to evaluate
      how visual search patterns (location and duration of gaze dwells and pupil size
      changes) altered when mammograms were repeatedly displayed. Two tests were
      performed. In the first test, a mammographer was shown the same mammogram on two
      occasions, separated by a 1-year interval. The second test evaluated the visual
      search patterns of four mammographers during a 30-minute display period, in which
      four mammograms were shown a variable number of times. Analysis of the gaze dwell
      data demonstrated that, although general recognition of a mammogram can occur
      within 1 second, even though 1 year separated the two occasions when the image
      was shown, repeated display of a mammogram may result in changes in (a) the time
      taken to reach a diagnosis, (b) the length of gaze dwell, (c) the total number of
      correct and incorrect diagnoses, and (d) pupillary constriction. Results from
      these tests may yield important information about how mammographers view images
      and how this process can affect diagnostic accuracy.

PMID- 10946698
TI  - The AAPM/RSNA physics tutorial for residents. Physics of SPECT.
AB  - Single-photon emission computed tomography (SPECT) provides three-dimensional
      (3D) image information about the distribution of a radiopharmaceutical injected
      into the patient for diagnostic purposes. By combining conventional scintigraphic
      and computed tomographic methods, SPECT images present 3D functional information
      about the patient in more detail and higher contrast than found in planar
      scintigrams. A typical SPECT system consists of one or more scintillation cameras
      that acquire multiple two-dimensional planar projection images around the
      patient. The projection data are reconstructed into 3D images. The collimator of
      the scintillation camera has substantial effects on the spatial resolution and
      detection efficiency of the SPECT system. Physical factors such as photon
      attenuation and scatter affect the quantitative accuracy and quality of SPECT
      images, and various methods have been developed to compensate for these image
      degrading effects. In myocardial SPECT, an important application of SPECT, recent
      use of attenuation compensation methods has provided images with reduced
      artifacts and distortions caused by the non-uniform attenuation in the chest
      region and by the diaphragmatic and breast attenuation. Attenuation-compensated
      myocardial SPECT images have the potential to improve clinical diagnosis by
      reducing the false-positive and false-negative detection of myocardial defects.
      In the future, further improvement in SPECT images will be realized from the
      continuous development of new radio-pharmaceuticals for new clinical
      applications, instrumentation with high spatial resolution and detection
      efficiency, and image reconstruction algorithms and compensation methods that
      reduce the image-degrading effects of the collimator-detector, attenuation, and
      scatter.

PMID- 10946700
TI  - General case of the day. Perforated Barrett ulcer of the distal esophagus.

PMID- 10946699
TI  - A clinical, noninvasive, MR imaging-monitored ultrasound surgery method.
AB  - A noninvasive method of tissue ablation that is guided and monitored with
      magnetic resonance (MR) imaging has been developed. The method uses sharply
      focused ultrasound transducers of different focal lengths to induce a localized
      temperature elevation during a short exposure (1-20 seconds). A hydraulic,
      computer-controlled positioning device moves the transducer in an MR imager. The
      positioner is built into a standard cradle in the imager. The system includes
      cavitation detection and power monitoring circuitry for patient safety. The
      target volume is outlined with cross-sectional MR images obtained immediately
      before sonication. By means of the software, the focus is moved to ablate the
      volume defined with the images. The temperature elevation during the exposure is
      monitored by means of the proton resonance frequency shift with fast gradient
      echo sequences, and the necrosed volume is demonstrated with T2-weighted fast
      spin-echo images. This method has been extensively tested in in vivo animal
      experiments and is now undergoing clinical trial.

PMID- 10946701
TI  - US case of the day. Adult-type granulosa cell tumor.

PMID- 10946702
TI  - Pediatric case of the day. Ectopic cervical thymus.

PMID- 10946703
TI  - Image interpretation session: 1995. Case 1. Exogenous lipoid pneumonia
      superimposed on systemic sclerosis with limited scleroderma (CREST syndrome).

PMID- 10946704
TI  - Image interpretation session: 1995. Case 2. Perforated duodenal duplication cyst
      causing pancreatitis.

PMID- 10946705
TI  - Image interpretation session: 1995. Case 3. Posttraumatic pseudoaneurysm of the
      azygos vein in a patient with azygos continuation of the IVC.

PMID- 10946706
TI  - Image interpretation session: 1995. Case 4. Small bowel webs due to NSAIDs
      ("diaphragm disease").

PMID- 10946707
TI  - Image interpretation session: 1995. Case 5. Cystic parafalcine meningioma with an
      associated intraparenchymal cyst.

PMID- 10946708
TI  - Image interpretation session: 1995. Case 6. Left atrial myxoma causing pulmonary
      edema.

PMID- 10946709
TI  - Image interpretation session: 1995. Case 7. Hepatic hematoma and left portal vein
      thrombosis due to an inappropriately placed umbilical vein catheter.

PMID- 10946710
TI  - Image interpretation session: 1995. Case 8. Angiogenesis in a liver transplant
      recipient with thrombosis of the primary arterial and left portal venous blood
      supply.

PMID- 10946711
TI  - Image interpretation session: 1995. Case 9. Radiographically lucent foreign
      material (plastic medication capsules) proximal to a postoperative small bowel
      stricture.

PMID- 10946712
TI  - Image interpretation session: 1995. Case 10. Angiomatous polyp of the nasopharynx
      (possible atypical angiofibroma).

PMID- 10946713
TI  - Transsaccadic memory for position and orientation of saccade source and target.
AB  - Participants made a saccade from one biological-motion figure to another and had
      to detect saccadecontingent changes in either the walker to which the eyes were
      sent (the target) or the walker that served as launch site (the source).
      Intrasaccadic displacements in both source and target were relatively hard to
      detect, whereas changes in the walkers' depth orientation were readily noticed,
      indicating that previous findings on within-object saccades generalize to between
      objects saccades. Contrary to predictions derived from theories that assign a
      privileged status to the saccade target, transsaccadic memory for the target's
      position and orientation was not more accurate than memory for the source.
      Displacements or rotations of one object toward the other object were more
      detectable than the same changes away from each other, suggesting that relational
      coding plays a prominent role in the integration of information across saccades.

PMID- 10946714
TI  - Multiple spatial correspondence effects on dual-task performance.
AB  - Three dual-task experiments were conducted to examine whether the underadditive
      interaction of the Simon effect and stimulus onset asynchrony (SOA) on Task 2
      performance is due to decay. The experiments tested whether the reverse Simon
      effect obtained with an incompatible stimulus-response (S-R) mapping would show
      an overadditive interaction with SOA, as predicted by R. De Jong, C.-C. Liang,
      and E. Lauber's (1994) dual-process model. Tone or letter identification tasks
      with vocal or keypress responses were used as Task 1. Task 2 was keypresses to
      arrow direction (or letter identity in Experiment 1). For all experiments, the
      normal Simon effect showed an underadditive interaction with SOA, but the reverse
      Simon effect did not show an overadditive interaction. The results imply that the
      dual-process model is not applicable to the dual-task context. Multiple
      correspondence effects across tasks implicate an explanation in terms of
      automatic S-R translation.

PMID- 10946716
TI  - Crossmodal links between vision and touch in covert endogenous spatial attention.
AB  - The authors report a series of 6 experiments investigating crossmodal links
      between vision and touch in covert endogenous spatial attention. When
      participants were informed that visual and tactile targets were more likely on 1
      side than the other, speeded discrimination responses (continuous vs. pulsed,
      Experiments 1 and 2; or up vs. down, Experiment 3) for targets in both modalities
      were significantly faster on the expected side, even though target modality was
      entirely unpredictable. When participants expected a target on a particular side
      in just one modality, corresponding shifts of covert attention also took place in
      the other modality, as evidenced by faster elevation judgments on that side
      (Experiment 4). Larger attentional effects were found when directing visual and
      tactile attention to the same position rather than to different positions
      (Experiment 5). A final study with crossed hands revealed that these visuotactile
      links in spatial attention apply to common positions in external space.

PMID- 10946715
TI  - Functional stabilization of unstable fixed points: human pole balancing using
      time-to-balance information.
AB  - Humans are often faced with tasks that require stabilizing inherently unstable
      situations. The authors explored the dynamics of human functional stabilization
      by having participants continually balance a pole until a minimum time criterion
      was reached. Conditions were manipulated with respect to geometry, mass, and
      characteristic "fall time" of the pole. Distributions of timing between pole and
      hand velocities showed strong action-perception coupling. When actions
      demonstrated a potential for catastrophic failure, the period of hand oscillation
      correlated well with the perceptual quantity "time to balance" (tau(bal) =
      theta/theta), but not other quantities such as theta and theta alone. This
      suggests that participants were using available tau(bal) information during
      critical conditions, although they may not have been attending to this type of
      perceptual information during typical, noncritical motions of successful
      performance. In a model analysis and simulation, the authors showed how discrete
      tau(bal) information may be used to adjust the parameters of a controller to
      perform this task.

PMID- 10946717
TI  - Visual word recognition: reattending to the role of spatial attention.
AB  - Three experiments examine whether spatial attention and visual word recognition
      processes operate independently or interactively in a spatially cued lexical
      decision task. Participants responded to target strings that had been preceded
      first by a prime word at fixation and then by an abrupt onset cue either above or
      below fixation. Targets appeared either in the cued (i.e., valid) or uncued
      (i.e., invalid) location. The proportion of validly cued trials and the
      proportion of semantically related prime-target pairs were manipulated
      independently. It is concluded that spatial attention and visual word recognition
      processes are best seen as interactive. Spatial attention affects word
      recognition in 2 distinct ways: (a) it affects the uptake of orthographic
      information, possibly acting as "glue" to hold letters in their proper places in
      words, and (b) it (partly) determines whether or not activation from the semantic
      level feeds down to the lexical level during word recognition.

PMID- 10946718
TI  - Dimension-based visual attention modulates dual-judgment accuracy in Duncan's
      (1984) one- versus two-object report paradigm.
AB  - Four experiments, adapting the object-judgment paradigm developed by J. Duncan
      (1984), examined the relationship between object-based and domain-based
      mechanisms of visual attention. The experiments demonstrated a cross-domain cost,
      in terms of accuracy, when observers made dual color-form judgments to one or two
      overlapping objects presented briefly, relative to within-domain, dual-color and
      dual-form judgments. This domain-based selection effect was additive to an object
      based effect, a cost of making dual judgments to separate objects, as reported by
      J. Duncan (1984). The pattern of object- and domain-based effects points to a
      capacity limitation in how multidimensional features are bound into a coherent
      object representation, consistent with the dimension-weighting account of H. J.
      Miller, D. Heller, and J. Ziegler (1995), which postulates that there is a limit
      to the total selection weight available to be allocated to an object's
      dimensions.

PMID- 10946719
TI  - A dual-task investigation of automaticity in visual word processing.
AB  - An analysis of activation models of visual word processing suggests that
      frequency-sensitive forms of lexical processing should proceed normally while
      unattended. This hypothesis was tested by having participants perform a speeded
      pitch discrimination task followed by lexical decisions or word naming. As the
      stimulus onset asynchrony between the tasks was reduced, lexical-decision and
      naming latencies increased dramatically. Word-frequency effects were additive
      with the increase, indicating that frequency-sensitive processing was subject to
      postponement while attention was devoted to the other task. Either (a) the same
      neural hardware shares responsibility for lexical processing and central stages
      of choice reaction time task processing and cannot perform both computations
      simultaneously, or (b) lexical processing is blocked in order to optimize
      performance on the pitch discrimination task. Either way, word processing is not
      as automatic as activation models suggest.

PMID- 10946720
TI  - Hierarchical motion organization in random dot configurations.
AB  - Motion organization has 2 aspects: the extraction of a (moving) frame of
      reference and the hierarchical organization of moving elements within the
      reference frame. Using a discrimination of relative motions task, the authors
      found large differences between different types of motion (translation,
      divergence, and rotation) in the degree to which each can serve as a moving frame
      of reference. Translation and divergence are superior to rotation. There are,
      however, situations in which rotation can serve as a reference frame. This is due
      to the presence of a second factor, structural invariants (SIs). SIs are spatial
      relationships persisting among the elements within a configuration such as a
      collinearity among points or one point coinciding with the center of rotation for
      another (invariant radius). The combined effect of these 2 factors--motion type
      and SIs-influences perceptual motion organization.

PMID- 10946721
TI  - Object features, object locations, and object files: which does selective
      attention activate and when?
AB  - The representation within which attention operates was investigated in 3
      experiments. The task was similar to that of R. Egly, J. Driver, and R. D. Rafal
      (1994). Participants had to detect the presence of a target at 1 of 4 ends of 2
      shapes, differing in color and form. A precue appeared at 1 of the 4 possible
      corners. The 2 shapes occupied either the same or different locations in the
      cuing and target displays. The results showed that the cued object location was
      attended whether or not space was task relevant, whereas the cued object features
      (color and form) were attended only when these were task relevant. Moreover, when
      object file continuity was maintained through continuous movement, attention was
      found to follow the cued object file as it moved while also accruing to the cued
      location.

PMID- 10946722
TI  - Attention and luminance detection: effects of cues, masks, and pedestals.
AB  - Three experiments investigated the effects of attention on the detection of
      luminance targets in a spatial-cuing paradigm. Gabor patch stimuli of 30, 60, or
      90 ms duration, equated for detectability, were presented (a) against a uniform
      field with a checkerboard backward mask, (b) atop a 15% luminance pedestal with a
      backward mask, or (c) atop a luminance pedestal with no backward mask. Signal
      detection analysis showed that detection sensitivity was significantly enhanced
      at attended locations for all observers when backward masks were used, both when
      targets were presented against a uniform field and when a pedestal was used.
      However, when no masks were used there was no cuing advantage of any kind. The
      results show that the cuing effect in simple detection depends on the use of
      backward masks, a finding that resolves the inconsistencies previously associated
      with studies of this type.

PMID- 10946723
TI  - Repetition priming reveals sustained facilitation and transient inhibition in
      reaction time.
AB  - Reaction time (RT) in a detection or a location discrimination task increases
      when a target is repeatedly presented at the same location (inhibition), whereas
      RT decreases in feature (color or orientation) discrimination tasks
      (facilitation; Y. Tanaka & S. Shimojo, 1996a). Here, the time course of
      inhibition and facilitation was examined, using a repetition priming paradigm.
      Results indicate that inhibition occurred only in the immediately successive
      trial, whereas facilitation accumulated over several trials with location
      repetition. Moreover, inhibition and facilitation occurred in a task-relevant
      manner: Detection-location discrimination tasks produced transient RT increase,
      whereas feature discrimination tasks produced cumulative RT decrease. These
      results suggest a functional dissociation between spatial orienting and feature
      analysis, as well as top-down modulations by tasks leading to different types of
      visual memory.

PMID- 10946724
TI  - Distortions in definite distance and shape perception as measured by reaching
      without and with haptic feedback.
AB  - Psychophysical studies reveal distortions in perception of distance and shape.
      Are reaches calibrated to eliminate distortions? Participants reached to the
      front, side, or back of a target sphere. In Experiment 1, feedforward reaches
      yielded distortion and outward drift. In Experiment 2, haptic feedback corrected
      distortions and instability. In Experiment 3, feedforward reaches with only
      haptic experience of targets replicated the shape distortions but drifted inward.
      This showed that outward drift in Experiment 1 was visually driven. In Experiment
      4, visually guided reaches were accurate when participants used binocular vision
      but when they used monocular vision, reaches were distorted. Haptic feedback
      corrected inaccuracy and instability of distance but did not correct monocular
      shape distortions. Dynamic binocular vision is representative and accurate and
      merits further study.

PMID- 10946725
TI  - Measurement error in subliminal perception experiments: simulation analyses of
      two regression methods.
AB  - A. G. Greenwald, M. R. Klinger, and E. S. Schuh (1995) investigated subliminal
      perception using a regression-based test for a dissociation between direct and
      indirect measures of perceptual ability. Direct and indirect measures were
      obtained for each observer, and a regression analysis was used to predict the
      amount of indirect perception at the point where the direct measure showed zero
      sensitivity. A significant positive intercept, obtained with both standard
      regression and a modified regression developed by K. C. Klauer, S. C. Draine, and
      A. G. Greenwald (1998), was used to argue for the key dissociation. When the
      assumptions of these methods are not met, however, simulations indicate that
      significant positive intercepts can often be obtained even if there is no
      dissociation. Moreover, the assumptions are theoretically implausible and
      inconsistent with some aspects of the results. Thus, the significant positive
      intercept is not strong evidence of the key dissociation.

PMID- 10946726
TI  - Investigating a memory-based account of negative priming: support for selection
      feature mismatch.
AB  - Using typical and modified negative priming tasks, the selection-feature mismatch
      account of negative priming was tested. In the modified task, participants
      performed selections on the basis of a semantic feature (e.g., referent size).
      This procedure has been shown to enhance negative priming (P. A. MacDonald, S.
      Joordens, & K. N. Seergobin, 1999). Across 3 experiments, negative priming
      occurred only when the repeated item mismatched in terms of the feature used as
      the basis for selections. When the repeated item was congruent on the selection
      feature across the prime and probe displays, positive priming arose. This pattern
      of results appeared in both the ignored- and the attended-repetition conditions.
      Negative priming does not result from previously ignoring an item. These findings
      strongly support the selection-feature mismatch account of negative priming and
      refute both the distractor inhibition and the episodic-retrieval explanations.

PMID- 10946728
TI  - Introduction: the growth of relational therapy.

PMID- 10946727
TI  - Occlusion, symmetry, and object-based attention: reply to Saiki (2000).
AB  - J. Saiki (2000) argued that, because the stimuli used by M. Behrmann, R. S.
      Zemel, and M. C. Mozer (1998) were confounded by symmetry, conclusions about
      whether amodally completed objects can benefit from object-based attention are
      unwarranted. Here, the authors examine J. Saiki's claim further and expand on
      their view of the mechanisms underlying object-based attention, suggesting that
      perceptual organization is the process whereby features from a single object are
      selectively attended. In light of this, they claim that heuristics such as
      symmetry and collinearity play an important role in the facilitation of features
      from a single object. In support of this claim, they present data from a further
      experiment using displays that exploit common fate, another grouping heuristic,
      and show that, under these conditions, the hallmark of object-based attention, a
      single-object advantage, is obtained for the occluded (amodally completed)
      shapes.

PMID- 10946729
TI  - The role of mutual empathy in relational/cultural therapy.
AB  - Central to the notion of healing in connection is the power of mutual empathy in
      the therapeutic relationship. Isolation is a major source of human suffering and
      is often accompanied by immobilization, which prevents movement back into
      relationship after disconnections. Healing is seen as occurring in connection
      with others. In order for patients to relinquish strategies of disconnection and
      shift their negative expectations in relationships, they must actually experience
      a sense of relational efficacy, of having an impact on the other person, the
      therapist. This happens when the therapist is emotionally present, attuned,
      therapeutically authentic, and working with the connections and disconnections in
      the therapy relationship itself. In this way, people begin to move back into
      growth-fostering relationships, expecting that others may respond empathically
      and finding that they can be effective in shifting and moving relationships in
      ways that allow them to bring themselves more fully into relationship, to be more
      whole and authentic.

PMID- 10946730
TI  - Relational diagnosis: a coconstructive-developmental perspective on assessment
      and treatment.
AB  - As we expand the borders of traditional diagnostic nomenclature, distinguishing
      health from disorder becomes complex. This is especially true when the diagnostic
      lens views individuals as they exist within families that reside within wider
      social milieus. From this viewpoint, the recursive and interdependent factors
      influencing how individuals, relationships, and wider collectives contribute to
      and construe disorder need to be determined Systemic Cognitive-Developmental
      Therapy is one approach to conducting viable relational diagnoses and treatment,
      guiding therapists to formulate an understanding of the internal cognitive
      developmental resources available to clients and other relevant, interdependent
      systems, and to examine the forces influencing the interactive discourse across
      these systems. The constructs of worldview, information processing styles, power
      differentials, and interpersonal connectiveness are presented as conceptual tools
      to guide relational diagnosis. An example illustrates relational diagnosis and
      treatment.

PMID- 10946731
TI  - The therapist-parent alliance in family-based therapy for adolescents.
AB  - This article describes procedures for developing a therapeutic alliance with a
      parent within the context of family therapy for adolescents. After an overview of
      the general clinical model, specific themes and interventions are described that
      provide a map to facilitate this process. Following Bordin's (1979) model,
      alliance is conceptualized in three parts: bonds, goals, and tasks. The bond
      phase consists of the therapist showing empathy and understanding toward the
      parent and the parent developing empathy toward their own life struggles. The
      goal phase consists of defining parent-child relationship building as a primary
      focus of treatment. The task phase consists of preparing parents to better
      communicate with their adolescent. These phases can occur sequentially within a
      single session with a parent alone. The alliance building session sets the
      foundation for parent-adolescent conflict resolution leading to reattachment in
      future sessions.

PMID- 10946732
TI  - Integrative relational therapy of complex clinical syndromes: ending the
      multigenerational transmission process.
AB  - The treatment of complex clinical syndromes poses a special challenge to the
      mental health clinician because of the interactions between the comorbid
      personality disorders and the clinical syndromes. Advancements in relational
      diagnosis and in the classification of dysfunctional personologic systems can
      orient and guide the clinician in making the most of sequential and multiple
      treatment modalities, and in intervening at systemic fulcrum points. Integrative
      Relational Therapy offers a model of treatment based on a biopsychosocial
      framework and systemic principles. In this article, a case example of a
      Narcissistic Dysfunctional Personologic System is presented and the treatment
      approach elaborated.

PMID- 10946733
TI  - Relational therapy in medical settings: working with somatizing patients and
      their families.
AB  - Psychotherapy for patients who present in a medical setting involves certain
      unique challenges, including the need to bridge the mind-body split. Somatizing
      patients, in particular, live at the interface of mind and body. Their physical
      symptoms may be biological markers as well as psychological metaphors and
      interpersonal communications. As such, it is important to assess and treat both
      patient and family, in collaboration with the healthcare team. We review three
      foundational principles for working with such families: biopsychosocial
      integration, development of a collaborative stance, and moving from "Either-Or"
      to "Both-And" thinking. An extended report of a patient with psychogenic seizures
      illustrates the use of nine treatment strategies: (1) Validate the reality of the
      problem, (2) involve the family, (3) work closely with the healthcare team, (4)
      enhance curiosity, (5) actively attend to somatic symptoms, (6) link the somatic
      and the psychological. (7) use physical interventions, (8) tolerate uncertainty
      and practice patience, and (9) terminate gently.

PMID- 10946734
TI  - What does the research tell us about couple and family therapies?
AB  - This article overviews for the practicing clinician the research assessing couple
      and family therapies. Research on couple and family therapies has established the
      overall efficacy of these forms of intervention as a general grouping, their
      value both as treatments and parts of treatments in ameliorating a number of
      disorders and difficulties, and the efficacy of a number of specific therapies
      aimed at specific difficulties. However, there remain several prominent couple
      and family therapies that have yet to be assessed through research, and the
      research has only begun to be able to inform specific therapist decision making.
      Findings from research assessing family process are cited that can prove useful
      to therapists.

PMID- 10946735
TI  - Concussion in sports and recreation.
AB  - More than 800 sports-related concussions occur in the United States each day,
      sometimes involving high-profile athletes whose injuries reach public awareness
      through sports broadcasts and news media. Although nonphysicians are often
      present and relied upon for the detection of concussion in the sports setting,
      the proper diagnosis and management of this neurological problem require a
      physician's thoughtful attention to the athlete's signs and symptoms. This
      article offers a diagnostic protocol and treatment recommendations as well as a
      useful grading scale and management strategy for return to competition.

PMID- 10946736
TI  - Cervical spine injuries in the athlete.
AB  - Special considerations must be brought into play when the physician is consulted
      about when to allow an athlete to return to play following injury. This is
      especially true for brain and spinal cord injury. Although it is generally best
      to be on the conservative side, being too reticent about allowing any athlete to
      return may be very detrimental to the athlete and/or the entire team. Therefore,
      it behooves the sports physician to be circumspect with regard to not only the
      type of injury the athlete has suffered but also the nature, duration, and the
      repetitive aspects of the trauma along with the inherent strengths of any player.
      This article will provide the sports physician with criteria for making sound
      decisions regarding return to competition after cervical spine injury and
      "functional" cervical spinal stenosis.

PMID- 10946737
TI  - Chronic traumatic brain injury associated with boxing.
AB  - Chronic traumatic brain injury (CTBI) associated with boxing occurs in
      approximately 20% of professional boxers. Risk factors associated with CTBI
      include increased exposure (i.e., duration of career, age of retirement, total
      number of bouts), poor performance, increased sparring, and apolipoprotein (APOE)
      genotype. Clinically, boxers exhibiting CTBI will present with varying degrees of
      motor, cognitive, and/or behavioral impairments. The severe form of CTBI is
      referred to as dementia pugilistica. The diagnosis of CTBI is dependent upon
      documenting a progressive neurological condition that is consistent with the
      clinical symptomatology of CTBI attributable to brain trauma and unexplainable by
      an alternative pathophysiological process. Pathologically, CTBI shares many
      characteristics with Alzheimer's disease (i.e., neurofibrillary triangles,
      diffuse amyloid plaques, acetylcholine deficiency, and/or tau immunoreactivity).
      The mainstay of treatment of CTBI is prevention, however medications used in the
      treatment of Alzheimer's disease and/or parkinsonism may be utilized.

PMID- 10946738
TI  - Neurologic injuries in baseball players.
AB  - In baseball pitchers, injuries to the throwing arm are common due to the extreme
      stresses placed on the elbow and shoulder joints. These result in peripheral
      nerve syndromes including ulnar neuropathy at the elbow and suprascapular
      neuropathy at the shoulder. Recurrent trauma to the axillary artery causing
      aneurysm and thrombus formation may lead to distal ischemia and stroke. Careful
      evaluation is required to identify musculoskeletal, neurologic, and vascular
      causes of upper extremity symptoms in the throwing athlete.

PMID- 10946739
TI  - Migraine in the athlete.
AB  - Migraine in the athlete may occur secondary to effort, prolonged exertion, or
      trauma or as a posttraumatic event. The chemistry is probably akin to that of
      spontaneous migraine. The purpose of this discussion is to outline the
      differential diagnosis of the athlete presenting with headache. Appropriate
      treatment can enhance athletic performance and enable the migraineur to
      participate in athletic endeavors.

PMID- 10946740
TI  - Neuromusculoskeletal syndromes in wheelchair athletes.
AB  - With the growth of wheelchair athletics at both grassroots and national levels,
      there has been an increased incidence of sports-related and overuse syndromes in
      the wheelchair-user population. This article provides an overview of the
      available literature on the incidence, prevalence, evaluation, prevention, and
      rehabilitative management of these types of clinical syndromes.

PMID- 10946741
TI  - High-altitude cerebral edema (HACE): the Denver/Front Range experience.
AB  - High-altitude cerebral edema (HACE) is a potentially fatal metabolic
      encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia
      of altitude. Symptoms commonly are headache, ataxia, and confusion progressing to
      stupor and coma. HACE is often preceded by symptoms of acute mountain sickness
      and coupled, in its severe form, with high-altitude pulmonary edema. Although
      HACE is mostly seen at altitudes above that of the Denver/Front Range visitor
      skier locations, we report our observations over a 13-year period of skier
      visitor HACE patients. It is believed that this is a form of vasogenic edema, and
      it is responsive to expeditious treatment with a successful outcome.

PMID- 10946742
TI  - Neurological complications of windsurfing (sailboarding).
AB  - This article presents a brief history of windsurfing, a relatively new
      recreational and competitive sport activity also known as sailboarding; a brief
      summary of physiologic studies of windsurfers; and a review of windsurfing
      injuries with a focus on the neurological complications of windsurfing.

PMID- 10946743
TI  - Peripheral nerve injuries in athletes: a case series of over 200 injuries.
AB  - We retrospectively reviewed electrodiagnostic (EDX) studies performed on 346
      athletes with sports injuries who were referred to our EDX laboratory from 1974
      to 1997. These injuries included 216 nerve root, plexus, or peripheral nerve
      injuries sustained by 180 of the athletes. Eighty-six percent of the injuries
      were to the upper extremity. Athletes with nerve fiber injuries participated in
      27 different sports, but over one third of injuries were sustained playing
      football. The most common symptomatic upper extremity injury was the "burner"
      (N=40). Forty-three athletes had median neuropathies, many of which were
      asymptomatic cases of carpal tunnel syndrome. Cervical radiculopathies (N=19) and
      axillary (N=22), ulnar (N=19), and suprascapular (N=14) mononeuropathies were
      also prevalent. The most common lower extremity injuries were peroneal
      neuropathies (N=17) and lumbosacral radiculopathies (N=7). This is the largest
      reported series of sports-related nerve injuries. The mechanisms of the most
      common nerve injuries are discussed.

PMID- 10946744
TI  - Neurologic injuries in skiers and snowboarders.
AB  - Neurologic injures are the leading cause of death and disability in skiing and
      snowboarding accidents, despite accounting for only a small fraction of injuries
      overall. Head injuries make up 3 to 15% of all skiing and snowboarding related
      injuries, spinal injuries account for 1 to 13%, and peripheral nerve injuries
      constitute less than 1% of reported injuries. Improvements in equipment and
      technology, especially advances in binding technology, have resulted in decreased
      injury rates on the slopes overall, but neurologic injury rates have not
      decreased, and in fact appear to be increasing as a percentage of overall
      injuries and in absolute numbers. With advances in technology and slope
      maintenance, skiers and boarders progress to higher skill levels and faster
      speeds more rapidly than ever before. Great efforts have been focused on reducing
      extremity injuries in skiers and snowboarders, but until recently very little
      attention has been given to neurologic injury prevention on the slopes. Hopefully
      with increased awareness and the growing popularity of ski/snowboard helmets, we
      will begin to see head injury rates (and maybe even spine injury rates) decrease
      among skiers and snowboarders.

PMID- 10946746
TI  - Neurology in the art museum: Andrew Wyeth's Christina's World.
AB  - Andrew Wyeth's painting of his friend and neighbor Christina Olson, Christina's
      World, arguably the best known picture by a living American painter, depicts a
      woman crawling across a field while gazing toward her house. Christina Olson had
      a lifelong slowly progressive paralytic disorder. Reflections on her life,
      clinical symptoms, medical evaluation, and her influence on Mr. Wyeth are
      presented herein.

PMID- 10946745
TI  - Hazards of bicycling: from handlebars to lightning.
AB  - The bicycle, an invention that provides joy and transportation to millions of
      people, can also be a source of disabling injuries and death. The victims of
      bicycle accidents are usually in good health and often young. Most of the fatal
      head injury cases are teenagers. In this article, I have chosen four areas of
      bicycle trauma that frequently brings the bicycle patient to the attention of a
      neurologist. These areas are (1) head trauma as a consequence of road collisions;
      (2) compressive ulnar neuropathy; (3) impotence, probably due to compression of
      the pudendal nerve or its branches; and (4) lightning-related bicycle injuries.
      The one thing that all four categories have in common is that they are often
      preventable. Helmet usage and common sense would lower the number of serious head
      trauma cases by 50%. Compressive ulnar and pudendal neuropathies can be prevented
      or reduced if the cyclist would frequently change his or her position in relation
      to the handlebar and saddle. In the majority of cases of compressive
      neuropathies, the symptoms improve if the patient takes a holiday from bike
      riding. Lightning injuries can be avoided or lessened if the cyclist takes
      proactive measures to limit his or her exposure during thunderstorms. These
      proactive measures include knowing the climate patterns of the area and knowing
      where the nearest safe shelter is located.

PMID- 10946747
TI  - Developing child mental health services in developing countries.
AB  - There is an urgent need to pay attention to the mental health of children in
      developing countries. Professionals confronted with this task face a number of
      challenges. Services have to be planned in a rational way, keeping in mind the
      needs of local populations. These needs will often exceed the available
      resources, and it will be necessary to set priorities. Feasible and cost
      effective models of service delivery then have to be developed to meet these
      needs. This annotation provides a framework within which mental health needs of
      children can be assessed, priorities established, and services organised. This is
      illustrated with examples of relevant activities undertaken in low-income
      developing countries over the last two decades.

PMID- 10946748
TI  - Autism and developmental receptive language disorder--a comparative follow-up in
      early adult life. I: Cognitive and language outcomes.
AB  - In this paper we compare adult outcome in a group of young men with autism and a
      group with developmental receptive language disorders. The two groups were first
      assessed in early childhood, when aged 7 to 8 years of age. Although matched at
      that time for nonverbal IQ (mean 92-93) and expressive language ability, the
      Autism group was significantly more impaired on most measures of social and
      communication skills and stereotyped behaviours. A later follow-up, in mid
      childhood, suggested that although the groups were still quite distinct, social
      and behavioural problems had become more apparent in the Language group. The
      current study was completed when the participants were aged, on average, 23 to 24
      years. The findings indicated that verbal IQ and receptive language scores had
      improved significantly more in the Autism group than in the Language group over
      time. Moreover, although the Language group were less severely impaired in their
      social use of language, many showed a number of abnormal features in this domain.
      There were no differences between the groups on tests of reading or spelling.
      Discriminant function analysis, which had clearly distinguished between the
      groups as children, now showed much greater overlap between them. Regression
      analysis indicated that although early language ability appeared to be related to
      outcome in the Autism group, in the Language group there was little association
      between measures of childhood functioning and later progress. The implications of
      these findings for understanding the nature of the underlying deficit in autism
      and the relationship between the two disorders are discussed.

PMID- 10946749
TI  - Autism and developmental receptive language disorder--a follow-up comparison in
      early adult life. II: Social, behavioural, and psychiatric outcomes.
AB  - This paper focuses on general social functioning in two groups of young men, one
      with autism and one with developmental receptive language disorders, who were
      first assessed at the ages of 7-8 years. At that time, although matched for
      nonverbal IQ (mean 92-93) and expressive language, the Language group showed
      significantly fewer social and behavioural problems. At follow-up, when aged on
      average, 23 to 24 years, the Autism group continued to show significantly more
      impairments in terms of stereotyped behaviour patterns, social relationships,
      jobs, and independence. However, problems in all these areas were also common in
      the Language group. Many still lived with their parents, few had close friends or
      permanent jobs, and ratings of social interaction indicated abnormalities in a
      number of different areas. On a composite measure of social competence only 10%
      of the Language group was assessed as having severe social difficulties compared
      to 74% of the Autism group. Nevertheless, 65% were rated as having moderate
      social problems and only 25% were rated as being of near/normal social
      functioning. Two individuals in the Language group, but none in the Autism group,
      had also developed a florid paranoid psychosis in late adolescence. As in the
      follow-up of cognitive and linguistic functioning (see Mawhood et al., 2000, this
      volume, pp. 547-559), discriminant function analysis, which had clearly
      distinguished between the groups as children, now showed much greater overlap
      between them. Regression analysis indicated that although early language ability
      appeared to be related to outcome in the Autism group, there was little
      association between any measures of childhood functioning and prognosis in the
      Language group. Theoretically, these findings have implications for our
      understanding of the nature of autism and other pervasive language disorders, and
      of the relationship between them. Practically, they demonstrate the very
      persistent problems experienced by individuals with developmental language
      disorders, and their need for much greater help and support than is presently
      available.

PMID- 10946752
TI  - Deaf children's understanding of emotions: desires take precedence.
AB  - Deaf children frequently have trouble understanding other people's emotions. It
      has been suggested that an impaired theory of mind can account for this. This
      research focused on the spontaneous use of mental states in explaining other
      people's emotions by 6- and 10-year-old deaf children as compared to their
      hearing peers. Within both age-groups deaf children referred to others' beliefs
      as often as their hearing peers and their references to desires even exceeded
      those of hearing children. This relative priority for the expression of desires
      is discussed in terms of possible communicative patterns of deaf children. The
      specific problems that deaf children meet in their daily communication might
      explain their abundance of desire-references: plausibly, they give a high
      priority to stress their own desires and needs unambiguously.

PMID- 10946751
TI  - Is preschool language impairment a risk factor for dyslexia in adolescence?
AB  - The literacy skills of 56 school leavers from the Bishop and Edmundson (1987)
      cohort of preschoolers with specific language impairment (SLI) were assessed at
      15 years. The SLI group performed worse on tests of reading, spelling, and
      reading comprehension than age-matched controls and the literacy outcomes were
      particularly poor for those with Performance IQ less than 100. The rate of
      specific reading retardation in the SLI group had increased between the ages of 8
      1/2 and 15 years and there had been a substantial drop in reading accuracy,
      relative to age. However, over 35% had reading skills within the normal range and
      those who had had isolated impairments of expressive phonology had a particularly
      good outcome. Our findings highlight the limitations of discrepancy definitions
      of dyslexia that do not take account of the changing demands of reading over
      time. We argue that children's phonological difficulties place them at risk of
      literacy failure at the outset of reading and that later, impairments of other
      language skills compromise development to adult levels of fluency.

PMID- 10946750
TI  - The familial aggregation of the lesser variant in biological and nonbiological
      relatives of PDD probands: a family history study.
AB  - OBJECTIVE: To determine the risk of the lesser variant (or PDD-like traits) in
      the biological and nonbiological second- and third-degree relatives of PDD
      probands using a screening questionnaire and to investigate the extent to which
      the risk of the lesser variant differs according to various characteristics of
      the proband. METHOD: The sample consists of a series of 34 nuclear families with
      2 affected PDD children (multiplex, MPX), 44 families with a single PDD child
      (simplex, SPX), and 14 families who adopted a PDD child. Data on characteristics
      of the lesser variant in 1362 biological and 337 nonbiological second- and third
      degree relatives were collected from parents by telephone interview and from
      several maternal and paternal relatives by questionnaire. RESULTS: All components
      of the lesser variant were more common in biological relatives (BR) than
      nonbiological relatives (NBR), confirming the familial aggregation of the traits.
      Proband characteristics associated with an increased risk of the lesser variant
      in relatives were a higher level of functioning and coming from a MPX family.
      CONCLUSIONS: These findings on the familial aggregation of the lesser variant
      suggest that the genes for PDD also confer susceptibility to the lesser variant
      and that PDD may be a genetically heterogeneous disorder.

PMID- 10946753
TI  - Phonological awareness of syllables, rhymes, and phonemes in deaf children.
AB  - Phonological awareness is important for reading development in hearing children,
      in whom it develops at the three consecutive levels of the syllable, rhyme, and
      phoneme. Deaf children typically have literacy difficulties, and previous
      research has been equivocal about whether deaf children can develop phonological
      awareness. Three experiments are presented that investigate the phonological
      skills of deaf children (mean age 11 years) at the three linguistic levels of
      syllable, rhyme, and phoneme. The first experiment showed that deaf children's
      syllable awareness can be equivalent to that of chronological age-matched hearing
      controls. In the second experiment, deaf children's ability to make rhyme
      judgements was above chance, but poorer than that of younger reading-matched
      hearing controls. The third experiment showed that deaf children could
      phonologically recode nonsense words at a level above chance, suggesting that
      they could draw on phonemic skills in certain conditions. We conclude that deaf
      children can develop phonological awareness, but that their phonological skills
      lag those of hearing children and may develop in different ways. Differences
      between our tasks and those used in other studies are discussed.

PMID- 10946754
TI  - Language and social cognition in children with specific language impairment.
AB  - This study explored the links between the development of language and the
      development of social cognition. Measures of language, phonological short-term
      memory, social cognition, and social competence of two groups of children with
      specific language impairment (SLI), one group attending a special school, the
      other attending integrated educational placements, were compared with those of
      chronological and language age-matched normally developing peers (N = 8 in each
      group). Significant differences between the scores of normally developing
      children and the scores of the group of children with SLI who attended the
      special school were found for social cognition and ratings of social competence.
      Children with SLI from integrated placements did not differ significantly from
      other groups on these measures. Assessments of language development and
      phonological short-term memory were not related to social cognition and social
      competence. Models of the possible relationship between social cognition and
      language development in children with SLI are discussed.

PMID- 10946755
TI  - Morphological alteration of temporal lobe gray matter in dyslexia: an MRI study.
AB  - Functional imaging studies of developmental dyslexia have reported reduced task
      related neural activity in the temporal and inferior parietal cortices. To
      examine the possible contribution of subtle anatomic deviations to these
      reductions, volumes were measured for the major lobes of the brain, the
      subcortical nuclei, cerebellum, and lateral ventricles on magnetic resonance
      imaging (MRI) scans from 16 right-handed dyslexic men, ages 18 to 40, and 14
      matched controls, most of whom had previously undergone PET imaging. A specific
      decrease in tissue volume was localized to the temporal lobes and was
      particularly prominent on the left (p < .01). An analysis of tissue composition
      revealed that this reduction was primarily attributable to decreased gray matter
      within the left temporal lobe (p < .002). Further segmentation of the temporal
      lobe showed that this reduction was not confined to the superior temporal gyrus,
      the primary location of primary auditory cortex. Reductions of temporal lobe gray
      matter may reflect a regional decrease in neuronal number or neuropil, which in
      turn may result in reading impairment.

PMID- 10946756
TI  - The Development and Well-Being Assessment: description and initial validation of
      an integrated assessment of child and adolescent psychopathology.
AB  - The Development and Well-Being Assessment (DAWBA) is a novel package of
      questionnaires, interviews, and rating techniques designed to generate ICD-10 and
      DSM-IV psychiatric diagnoses on 5-16-year-olds. Nonclinical interviewers
      administer a structured interview to parents about psychiatric symptoms and
      resultant impact. When definite symptoms are identified by the structured
      questions, interviewers use open-ended questions and supplementary prompts to get
      parents to describe the problems in their own words. These descriptions are
      transcribed verbatim by the interviewers but are not rated by them. A similar
      interview is administered to 11-16-year-olds. Teachers complete a brief
      questionnaire covering the main conduct, emotional, and hyperactivity symptoms
      and any resultant impairment. The different sorts of information are brought
      together by a computer program that also predicts likely diagnoses. These
      computer-generated summary sheets and diagnoses form a convenient starting point
      for experienced clinical raters, who decide whether to accept or overturn the
      computer diagnosis (or lack of diagnosis) in the light of their review of all the
      data, including transcripts. In the present study, the DAWBA was administered to
      community (N = 491) and clinic (N = 39) samples. There was excellent
      discrimination between community and clinic samples in rates of diagnosed
      disorder. Within the community sample, subjects with and without diagnosed
      disorders differed markedly in external characteristics and prognosis. In the
      clinic sample, there was substantial agreement between DAWBA and case note
      diagnoses, though the DAWBA diagnosed more comorbid disorders. The use of
      screening questions and skip rules greatly reduced interview length by allowing
      many sections to be omitted with very little loss of positive information.
      Overall, the DAWBA successfully combined the cheapness and simplicity of
      respondent-based measures with the clinical persuasiveness of investigator-based
      diagnoses. The DAWBA has considerable potential as an epidemiological measure,
      and may prove to be of clinical value too.

PMID- 10946758
TI  - Extracting meaning from comorbidity: genetic analyses that make sense.
AB  - As behavioral genetic strategies have become part of the arsenal of research in
      developmental psychopathology, a wide variety of genetic analyses are being
      applied to child psychiatric data. Multivariate genetic techniques have been used
      to explore comorbidity among traits or disorders and the main analysis undertaken
      has been to examine whether comorbidity is due to shared genetic and/or
      environmental factors. However, this model ignores other possible causes of
      comorbidity, which are reviewed. In particular, genetic analyses of comorbidity
      have only infrequently considered the model of phenotypic causality (one disorder
      directly influencing another), which provides an important alternative with
      potentially different implications for intervention strategies. Data from a
      recently published article by Wamboldt, Schmitz, and Mrazek (1998) are used to
      illustrate the potential difficulties of distinguishing between models of shared
      genetic/environmental risk and phenotypic causality. Given that the sample sizes
      required to distinguish between these models are often large, and frequently
      greater than those of the datasets available, it is argued that researchers
      should select the models that they test based on other lines of evidence that
      these models are plausible. Where convincing evidence does not exist, researchers
      should explore alternative models and determine their power to discriminate
      between these models.

PMID- 10946757
TI  - Social phobia and the persistence of conduct problems.
AB  - Recent epidemiological studies suggest that both social anxiety and attention
      deficit hyperactivity disorder (ADHD) in childhood might predict levels of
      delinquent behavior in adolescence. The current study prospectively examines the
      influence of social phobia and ADHD symptom scale scores on the correlation in
      conduct disorder symptom scale scores over time. An epidemiologically selected
      sample of 776 young people living in Upstate New York received DSM-based
      psychiatric assessments in 1983, 1985, and 1992 using structured interviews.
      Correlations among conduct disorder scales over time were examined as a function
      of social phobia and ADHD ratings. Individuals with low scores on social phobia
      scales or high scores on ADHD scales exhibited the highest correlation in conduct
      disorder symptom scales over time. There was also a suggestion that low scores on
      social phobia scales predicted later risk for conduct disorder. Low scores on
      social phobia symptom scales or high scores on ADHD scales predict stronger
      across-time correlations in conduct disorder symptom scales. Various cognitive or
      biological factors might account for these moderating effects on conduct
      problems.

PMID- 10946759
TI  - Burnout and health among Dutch dentists.
AB  - In this study, it was hypothesised that dentists with a high burnout risk would
      experience more health complaints and show more unhealthy behaviour when compared
      with dentists with a low burnout risk. With a response rate of 75%, a
      representative group of 709 actively practising dentists responded to a
      questionnaire containing the Dutch version of the Maslach Burnout Inventory (MBI
      NL), a health complaints measure (VOEG), and items on health behaviour. Results
      showed that dentists with a high burnout risk reported health complaints to a
      greater extent than dentists with a low burnout risk. They also reported more
      unhealthy behaviour in some aspects (physical exercise/sporting, increase in
      alcohol consumption, unhealthy diet), but not in others. It also appeared that
      one out of ten dentists reported having poor general health, and that three out
      of ten reported to have poor physical condition. In general, dentists' self
      reports appeared favourable in comparison with the Dutch population. It is
      concluded from this study that among dentists burnout and poor health are
      strongly related. It is discussed that in order to deal preventively with burnout
      in dentistry, attention to physical health, including ergonomics, is essential.

PMID- 10946760
TI  - Characteristics of adult dentally fearful individuals. A cross-cultural study.
AB  - This cross-cultural study investigated adult dental fear patients in three
      countries. A joint intake interview questionnaire and a dental anxiety scale
      explored the level, background and concomitant factors of dental anxiety among
      patients at the Universities of Tel Aviv (Israel), Goteborg (Sweden), and
      Pittsburgh (USA). It was shown that patients at all three sites were quite
      similar with regard to age, sex, level of dental anxiety (DAS) and avoidance
      time. Negative emotions were common, with more negative everyday life effects
      among Swedish patients. Regardless of country, most patients stated that they had
      always been fearful, but environmental etiologic factors were frequently
      reported. Swedish patients more often reported both direct and indirect learning
      patterns than Israeli patients. Patients' motivation for treatment was high,
      while the belief in getting fear reduction was clearly lower. The most common
      reason for Israeli patients to seek treatment was a personal decision to try to
      cope with the situation, while for Swedish patients it was pain. Israeli and US
      patients preferred more 'active' modes of treatment such as behavioral management
      therapies, while Swedish patients equally preferred active and more 'passive'
      treatment approaches such as general anesthesia. Preference for dentist
      attributes were similar among groups and underlined the strong emphasis that
      fearful individuals place upon dentists' behaviors and their performance of
      dentistry.

PMID- 10946761
TI  - Oral status of 35 subjects with eating disorders--a 1-year study.

PMID- 10946762
TI  - Metalloproteinase expression in normal and malignant oral keratinocytes:
      stimulation of MMP-2 and -9 by scatter factor.
AB  - Matrix metalloproteinases (MMPs) are Zn2+ dependent proteases produced by a
      variety of cell types. They have a fundamental role in tissue remodelling, tumour
      invasion and metastasis. Scatter factor (SF), secreted by fibroblasts, has a
      paracrine action on epithelial cells and binds the trans-membrane c-met receptor
      inducing loss of adhesion, cell motility and invasiveness in vitro. The purpose
      of this study was to test if SF can regulate the production of MMPs by epithelial
      cells. Supernatants from oral squamous cell carcinoma-derived cells (H375 and
      H376), a human keratinocyte line (UP), and primary cultures of oral mucosal
      keratinocytes, grown in the presence or absence of SF, were analysed using 0.1%
      gelatin zymography. MMPs were characterised by comparison with human recombinant
      enzymes and by the use of specific inhibitors. Oral mucosal keratinocytes, UP,
      and H357 cells expressed MMP-2 and MMP-9, whilst H376 cells only expressed MMP-2.
      SF increased the expression of MMP-9 in UP and MMP-2 in H376 supernatants. Both
      MMP-2 and MMP-9 activity were increased in H357 and normal keratinocyte
      supernatants. This could be blocked using a human recombinant anti-SF antibody.
      In all epithelial lines tested, c-Met, the cell surface receptor for SF, could be
      detected. The results indicate that SF stimulates MMP expression in UP, H376,
      H357, and normal oral mucosal cells and points to a role for SF in the regulation
      of oral keratinocyte behaviour in wound healing and neoplasia.

PMID- 10946764
TI  - Delay of tooth eruption in null mice devoid of the type I IL-1R gene.
AB  - Interleukin-one alpha (IL-1alpha) is located in the stellate reticulum and its
      receptor, type I IL-1R (IL-1R), is present in the adjacent dental follicle. IL
      1alpha may play a role in initiating tooth eruption because of its ability to
      enhance the gene expression in the dental follicle of putative tooth eruption
      molecules colony-stimulating factor-one (CSF-1). monocyte chemotactic protein-1
      (MCP-1), and nuclear factor kappa B (NFkappa-B). To directly examine the effect
      of IL-1alpha and IL-1R on tooth eruption, we observed the times of tooth eruption
      in null mice devoid of the type I IL-1R gene. The results showed that the time of
      eruption in the null mice was delayed by 2 d for the first mandibular molar and 1
      d for incisors as compared to wild type controls. Reverse transcription
      polymerase chain reaction (RT-PCR) techniques confirmed the absence of the IL-1R
      gene in the null mice, but the genes for CSF-1 and NFkappaB were still expressed.
      Thus, a molecule(s) other than IL-1alpha also may enhance the expression of CSF-
      and NFkappaB in the dental follicle. Because there is a slight delay of tooth
      eruption in IL-1R null mice, IL-1alpha may normally play a role in eruption.
      However, eruption eventually can occur without the signaling from IL-1alpha.

PMID- 10946763
TI  - Preproinsulin I and II mRNA expression in adult rat submandibular glands.
AB  - Mammalian salivary glands are known to produce a number of biologically active
      peptides. The aim of this study was to extend our previous results showing the
      presence of a biologically active insulin-like immunoreactive peptide in rat
      salivary glands. In rodents, where two nonallelic and functional insulin genes
      are expressed, the co-expression of both genes seems to be limited to beta-cells
      of pancreatic islets or to embryologic developmental processes. We have
      investigated the expression of insulin genes in rat submandibular glands and in a
      murine immortalized submandibular cell line, SCA-9. For this purpose, total RNAs
      were isolated and submitted to reverse transcription. The cDNAs obtained were
      amplified by a nested polymerase chain reaction using rat preproinsulin I and II
      primers. Our data show that both preproinsulin I and II mRNAs are expressed in
      adult rat submandibular glands as well as in the SCA-9 cell line. The
      identification of salivary gland rat preproinsulin I and II was confirmed by
      direct sequencing. These results provide, for the first time, evidence for the
      expression of both preproinsulin I and II mRNA in an extra-pancreatic tissue from
      adult rodents.

PMID- 10946765
TI  - Cloning, characterization and immunolocalization of human ameloblastin.
AB  - Amelogenesis imperfecta is a broad classification of hereditary enamel defects,
      exhibiting both genetic and clinical diversity. Most amelogenesis imperfecta
      cases are autosomal dominant disorders, yet only the local hypoplastic form has
      been mapped to human chromosome 4q between D4S242 1 and the albumin gene. An
      enamel protein cDNA, termed ameloblastin (also known as amelin and sheathlin),
      has been isolated from rat, mouse and pig. Its human homolog has been mapped to
      chromosome 4q21 between markers D4S409 and D4S400, flanking the local hypoplastic
      amelogenesis imperfecta critical region. Therefore, ameloblastin is a strong
      candidate gene for this form of amelogenesis imperfecta. To facilitate genetic
      studies related to this dental disease, we isolated and characterized a human
      ameloblastin cDNA. A human third molar cDNA library was screened and two
      ameloblastin clones identified. Nucleotide sequencing of these cDNAs indicated
      alternative splicing of the putative open reading frame, use of different
      polyadenylation signals, and a high degree of similarity to reported rat, mouse
      and porcine cDNAs. Immunohistochemistry studies on embryonic human teeth using an
      antibody to recombinant ameloblastin indicated ameloblastin expression by
      ameloblasts with localization in the enamel matrix associated with the sheath
      structures.

PMID- 10946766
TI  - In vitro synchronization of embryonic mouse incisor preodontoblasts and
      preameloblasts: repercussions on terminal differentiation.
AB  - Preodontoblasts divide asynchronously and their terminal differentiation occurs
      gradually. Experimental data suggested that the expression of competence by
      preodontoblasts to respond to specific epigenetic signals, triggering their overt
      differentiation, requires a minimal number of cell cycles. The intrinsic timing
      mechanism could imply division counting and preodontoblasts of juxtaposed cell
      generations might sequentially withdraw from the last physiological cycle. To
      test such an hypothesis, embryonic mouse lower incisors were cultured in vitro
      and treated sequentially with nocodazole in order to induce a transitory
      synchronization of the dividing preodontoblasts and preameloblasts. This
      synchronization led to a disorganization of the physiological gradual terminal
      differentiation of the odontoblasts, giving rise to three distinct domains
      comprising respectively: 1) odontoblasts with altered polarization and predentin
      secretion; 2) odontoblasts demonstrating equivalent polarization and predentin
      deposition; and 3) preodontoblasts-odontoblasts involved in gradual terminal
      differentiation. These results strongly suggest that the gradient of odontoblast
      functional differentiation results from sequential withdrawal from asynchronous
      cell cycles of competent cells able to overtly differentiate.

PMID- 10946767
TI  - Quantitative image analysis of hyaluronan expression in human tooth germs.
AB  - The expression of hyaluronan in human tooth germs was studied by using a
      biotinylated hyaluronan-binding complex and quantitative digital image analysis.
      At the cap stage, dental papilla exhibited a moderate staining, while intense
      reaction was observed in the apical portion of presecretory ameloblasts, stellate
      reticulum, and in dental basement membrane. When the enamel and dentine matrices
      started to develop, a strong hyaluronan reaction was evident in the young enamel
      and the apical portion of secretory ameloblasts. No hyaluronan could be detected
      in the secretory ameloblasts and enamel matrix of the early (9-wk-old) post-natal
      stage. It is concluded that hyaluronan may play a transitory role in the early
      phase of the development of the enamel matrix organization. A very weak signal
      was observed in the wall of dentin tubules, whereas the rest of the dentine
      matrix was not stained. The odontoblasts and the pulp were also moderately
      stained, and these reactions gradually decreased with age, suggesting that
      hyaluronan may also contribute to the development of dentine matrix and pulp.

PMID- 10946768
TI  - Effect of lead, cadmium and zinc on the activity of enamel matrix proteinases in
      vitro.
AB  - Environmental contamination with heavy metals leads to their uptake by the body.
      Dental tissues are known to harbor metals in concentrations related to the
      exposure at the time of dentin or enamel formation. Several enzymes involved in
      the metabolism of extracellular matrix components have been shown to be inhibited
      by excess metal ions. Enamel matrix proteinases seem to play a central role in
      the maturation of dental enamel, and inhibition of these enzymes by metals could
      interfere with amelogenesis. We have investigated the effect of lead, cadmium and
      zinc on the activity of enamel matrix proteinases using a colorimetric assay,
      casein and gelatin zymography, and an assay of enamel protein degradation in
      vitro. All three metals inhibited the proteolysis, as shown by the three methods
      employed, in concentrations as low as 110 microM. This study showed that
      contaminant metals can inhibit proteinolysis when a crude enamel extract
      containing enamel proteases is tested in vitro. Therefore, the presence of heavy
      metals in enamel matrix could interfere with amelogenesis due to alteration in
      normal proteolysis.

PMID- 10946769
TI  - Substitutes for methylene chloride as dental softening agent.
AB  - Methylene chloride is used as softening agent for guttapercha and as adhesion
      promotor for polymethylmethacrylate (PMMA). However, methylene chloride has been
      found to be carcinogenic. It was the aim of the present work to search for
      harmless substitutes for methylene chloride in these situations. A number of
      possible candidates with structural similarities to guttapercha or PMMA were
      selected. The efficacy in softening of guttapercha of these compounds was
      measured by the depth of penetration of a needle under the load of 2 N. The
      effect of the compounds on the adhesion between PMMA and an acrylic rebasing
      material was measured in shear. It was found that a number of alkenes or
      dialkenes of moderate molecular weight (1,3-pentadiene, cyclopentene, isoprene, 2
      methyl-2-butene, and 1,5-hexadiene) were as effective as methylene chloride as
      softening agent for guttapercha. As adhesion promotor in bonding to PMMA, it was
      found that low molecular weight methyl esters (methyl formate and methyl acetate)
      were as effective as methylene chloride. Because of the variation in polarity,
      the calculated solubility parameter was not a reliable predictor of softening
      efficacy of the investigated compounds.

PMID- 10946770
TI  - Elution of TEGDMA and BisGMA from a resin and a resin composite cured with
      halogen or plasma light.
AB  - Plasma arc light units for curing resin composites have been introduced with the
      claim of relatively short curing times. The purpose of the present study was to
      measure and compare elution of monomers from an experimental BisGMA-TEGDMA resin
      and a commercial resin composite when cured with a halogen unit and when cured
      with a plasma arc unit. Specimens of the materials were immersed in methanol, and
      the amounts of monomers released with time were analyzed by HPLC. By use of
      Fick's laws of diffusion, the amount of eluted monomers from the specimen at
      infinity was estimated. The elution from resin specimens and from resin composite
      specimens cured with the plasma arc light unit was 7 and 4 times higher,
      respectively, compared to the elution from specimens cured with the halogen unit.
      It was concluded that the plasma arc light curing unit did not provide optimal
      cure when used as recommended by the manufacturer.

PMID- 10946771
TI  - The nanoleakage phenomenon: influence of different dentin bonding agents,
      thermocycling and etching time.
AB  - "Nanoleakage" takes place within the hybrid layer zone of the dentin-composite
      interface in spaces not occupied by polymerized resin. The purpose of this study
      was to quantify the amount of nanoleakage in specimens treated with one of six
      different bonding agents. For one agent, different etching times were used, and
      for two agents results after thermocycling were obtained. Standardized class V
      cavities were prepared in 165 extracted human molars with cervical margins
      located in dentin. After placement of the composite using bonding agents, the
      teeth were stored in a 1% rhodamin-B-isothiocyanate solution for 24 h at 20
      degrees C, embedded in methacrylate, and sectioned parallel to the long axis of
      the tooth. A confocal laser scanning microscope was used to visualize a layer 10
      microm below the prepared surface of the section. The lengths of the penetrated
      pathways were measured, representing the amount of nanoleakage. In all materials
      tested, penetration pathways appeared within the hybrid layer in absence of gap
      formation. Penetration lengths of the tested materials were in a range from 69 +/
      24 microm to 469 +/- 333 microm. Thermocycling had no statistically significant
      influence, and etching for 15 s resulted in statistically significantly shorter
      penetration compared to longer etching.

PMID- 10946772
TI  - Nonoperative management of bile leaks following liver transplantation.
AB  - The biliary anastomosis has been called 'the Achilles heel' of liver
      transplantation (RABKIN JM, ORLOFF SL, REED MH. Transplantation 1998: 65 [2]:
      193; DAVIDSON BR, RAI R, KURZAWINSKI TR. Br J Surg 1999: 86 [4]: 447). Biliary
      complications after liver transplantation reportedly occur at an incidence of 20
      30%, 10-15% as bile leaks. The management of bile leaks, especially early bile
      leaks, is controversial. In the present study, we report our experience with the
      management of bile leaks after liver transplantation. In this retrospective
      study, we reviewed 85 liver transplants over a 3-yr period. In 79, the biliary
      anastomosis was choledochocholedochostomy (CDCD) over a small-caliber T-tube,
      while choledochojejunostomy (CDJ) was used in 7. Over a mean follow up period of
      13.5 months (median 10 months), 10 patients (12%) experienced a clinically
      significant bile leak within the first 3 months after liver transplantation. The
      early leaks, occurring within 1 month of transplant, were successfully managed by
      observation (DAVIDSON BR, RAI R, KURZAWINSKI TR. Br J Surg 1999: 86 [4]: 447) or
      endoscopic retrograde cholangiopancreatography (ERCP) and the placement of a
      biliary stent for a duration of 6-12 wk (RANDALL HB, WACHS ME, SOMBERG KA.
      Transplantation 1996: 61 [2]: 258). One of these resulted from accidental
      dislodgement of the T-tube on postoperative day 1; one resulted from necrosis at
      the CDCD anastomosis and required CDJ; the remaining four resulted from leaks
      along the T-tube track. One of the late leaks occurred following the planned
      removal of the T-tube at 3 months after liver transplantation; the other two were
      leaks along the T-tube track. All were successfully treated by ERCP and stent
      placement, though in one case, ERCP was initially unsuccessful because of the
      inability to advance a guidewire, necessitating a fluoroscopically aided guide
      wire placement during a mini laparotomy. ERCP was then successfully performed
      with the placement of a stent. [See table in text] CONCLUSIONS: Our experience
      indicates that most bile leaks after liver transplantation, including early
      leaks, can be successfully managed nonoperatively. Most will require
      intervention, but ERCP and stent placement are usually sufficient.

PMID- 10946773
TI  - Piggyback technique and selective use of veno-venous bypass in adult orthotopic
      liver transplantation.
AB  - BACKGROUND: The piggyback technique (PT), with preservation of the cava, is being
      used more frequently in adult orthotopic liver transplantation (OLT). The
      advantages of PT include hemodynamic stability during the anhepatic phase without
      a large-volume fluid infusion and obviating the need for veno-venous bypass
      (VVB). At our center, we changed our practice in July 1997 from the standard
      technique (ST) of OLT with routine use of VVB to PT and selective use of VVB. The
      purpose of the present study was to analyze the results with the two different
      practices, ST-routine VVB versus PT-selective VVB. METHODS: Forty OLTs were
      performed during the period July 1995 July 1997 using ST-routine VVB (group I)
      and 36 during August 1997-December 1998 using PT-selective VVB (group II). The
      etiology of liver disease was similar in the two groups, with hepatitis C and
      alcoholic liver disease accounting for half of the patients in each group. The
      UNOS status, age, sex, and percentage of patients with previous upper abdominal
      surgery were also similar between the two groups. RESULTS: In the PT-selective
      VVB era (group II), 34/36 patients (94%) underwent OLT with PT and VVB was used
      for 8 (22%) patients. The decision to use VVB was elective for 3 patients
      (fulminant hepatic failure, 2; severe portal hypertension, 1) and urgent for 5
      patients (hemodynamic instability during hepatectomy). The intraoperative use of
      packed red blood cells (PRBC) (mean +/- SD) was 15+/-12 units for group I and 9+/
      8 units for group II (p = 0.023). Anastomosis time and total operating time (mean
      +/- SD) were 91 + 30 min and 9.5+/-3.2 h, respectively, for group I patients
      compared with 52+/-28 min and 7.6+/-1.6 h, respectively, for group II patients
      (p<0.0001 and 0.002, respectively). Median post-operative stays in the intensive
      care unit (ICU) and in the hospital were 5 and 17 d, respectively, for group I
      and 4 and 11 d, respectively, for group II (p = NS). Mean serum creatinine on day
      3 was similar in the two groups. Median hospital charges for group I patients
      were $105439 compared with $91779 for group II patients (p = NS). The 1-year
      actuarial graft and patient survival rates were 78% and 82%, respectively, for
      group I, and 92% and 95%, respectively, for group II. CONCLUSIONS: PT is safe and
      can be performed in the majority of adult patients (>90%) undergoing OLT. With
      the routine application of the piggyback procedure, the use of VVB has been
      reduced to 20% of OLTs at our center. The practice of piggyback technique with
      the selective use of VVB is associated with shorter anhepatic phase and total
      operating time, lower blood product use, a trend towards shorter hospital length
      of stay, and reduced hospital charges compared with standard technique of OLT
      with routine use of VVB.

PMID- 10946774
TI  - Hospital charges following simultaneous kidney--pancreas transplantation: enteric
      drainage versus bladder drainage.
AB  - BACKGROUND: Enteric drainage (ED) is associated with reduced morbidity compared
      with bladder drainage (BD) after simultaneous kidney-pancreas transplantation
      (SKPT) and is becoming increasingly common (more than 50% of SKPTs done in the US
      in 1998 were performed with enteric drainage). Although several studies have
      reported the morbidity and graft survival of ED compared with BD previously,
      there are limited data available comparing the length of stay and hospital
      charges between these two drainage procedures. METHODS: Fourteen SKPTs were
      performed during the period January 1995 May 1998 using BD and 20 during June
      1998-August 1999 using ED. Hospital charges analyzed included the following
      categories: pharmacy, inpatient room, laboratory, operating room, medical
      surgical supply, radiology/nuclear medicine, and miscellaneous. Organ acquisition
      charges and professional fees were not included in this analysis. RESULTS: The
      mean hospital stay for patients with ED was 7.8+/-2.2 d (range 5-12 d; median 7.5
      d) compared with 15.9+/-7 d (range 8-38 d; median 15 d) for patients with BD (p =
      0.002). The mean hospital charges during initial hospitalization for the ED group
      were $36 582+/-11 424 compared with $64 555+/-29 054 for the BD group (p =
      0.005). There was a significant decrease in the charges relating to pharmacy,
      inpatient room, laboratory, radiology/nuclear medicine, and miscellaneous
      category in the ED group compared with the BD group, while the charges relating
      to operating room and medical-surgical supply were no different between the two
      groups. One-year actuarial kidney and pancreas graft survival rates were 83% and
      93%, respectively, for the BD group and 90% and 80%, respectively, for the ED
      group (p = NS). CONCLUSIONS: SKPT patients with ED had a 43% reduction in
      hospital charges and equivalent pancreas and kidney graft survival rates compared
      with SKPT patients with BD. A shorter hospital stay and a reduction in pharmacy,
      radiology/nuclear medicine, and laboratory charges contributed to the decreased
      hospital charges in SKPT patients with ED.

PMID- 10946775
TI  - Roux-en-Y venting jejunostomy in pancreatic transplantation: a novel approach to
      monitor rejection and prevent anastomotic leak.
AB  - INTRODUCTION: Pancreatic transplantation (PTx) with portal venous delivery of
      insulin and enteric drainage of the exocrine secretion is more physiologic than
      bladder-systemic (BS) drainage. With portal-enteric (PE) PTx, the diagnosis of
      acute rejection (AR) requires a percutaneous biopsy. The roux-en-y (RNY) venting
      jejunostomy in patients with PEPTx offers a novel approach to monitor rejection
      and prevent anastomatic leaks. METHODS: From January 1996 to December 1998, we
      performed 17 simultaneous kidney/pancreas transplants (SKPTx). The initial 4
      patients underwent BS drainage and the subsequent 13 patients underwent RNY
      venting jejunostomy with PE drainage. All patients were treated with quadruple
      therapy. There were 9 males, 14 patients were Caucasian with a mean age of 32 yr
      (range 30-54 yr), and a mean pre-transplantation duration of diabetes of 25 yr.
      Six patients underwent endoscopic donor duodenal biopsy through the jejunostomy
      to rule out clinically suspected AR. Gastrograffin was inserted into the
      jejunostomy to examine the integrity of anastamosis when indicated. In 9 out of
      13 patients, the venting jejunostomy was taken down 9-12 months post
      transplantation after allograft function was stable. RESULTS: Actual patient,
      kidney, and pancreas graft survival rates were 100, 100 and 94%, respectively,
      after a mean follow-up of 16 months. Renal allografts functioned immediately in
      89% of patients. The mean length of hospital stay was 19 d. Four (23%) patients
      (2 with BS drainage and 2 with PE drainage) suffered an AR episode in the first
      month, and 4 (23%) patients had five AR from 3-36 months post-transplantation.
      Other complications were post-operative bleeding in 3 patients, wound infection
      in 2 patients and a proximal duodenal stump leak in 1 patient. In patients with
      clinical rejection, endoscopy through the venting jejunostomy showed inflamed,
      friable doudenal mucosa and doudenal biopsy findings were compatible with AR.
      CONCLUSION: These preliminary results suggest that RNY venting jejunostomy with
      PE drainage can be used safely to diagnose and monitor pancreas AR and to
      diagnose and prevent anastamotic leaks. This technique will be even more useful
      to visualize transplanted duodenal mucosa, collect pancreatic secretions
      (amylase) for analysis and perform endoscopic retrograde cholangiopancreatography
      if needed to obtain pancreatic biopsies.

PMID- 10946776
TI  - Implication of advanced donor age on the outcome of liver transplantation.
AB  - Historically, age has been considered to be a relative contraindication for organ
      donors. The use of elderly donors for liver transplantation remains controversial
      due to the fear of inferior outcome. According to United Network for Organ
      Sharing (UNOS) data, the proportion of older donors has been increasing annually.
      This study describes the short- and long-term outcomes for transplantation of
      elderly donor livers. Three hundred and seventy-four primary liver
      transplantations, which had been performed at the University of Virginia Health
      System from 7 February 1988 to 31 December 1998, were included. Graft survival,
      incidence of primary non-function, and hepatic artery thrombosis (HAT) after
      transplantation according to the different age groups of liver donors were
      analyzed. Cases were analyzed by donor age (group I, n = 106: aged < 20 yr; group
      II, n = 217: aged between 20 and 49 yr; group III, n = 51: aged > or =50 yr), and
      by donor age in comparison with recipient age (group IV, n = 65: recipients
      transplanted with organs from donors within 5 yr of their age; group V, n = 266:
      recipients from donors > 5 yr younger than their age; group VI, n = 43:
      recipients from donors > 5 yr older than their age). Group III or VI (group of
      advanced donor age) and group II or V (control group) were compared by age,
      gender, race, body weight, height, pre-transplantation cytomegalovirus (CMV)
      status of the recipients donors, cause of brain death of donors, total or warm
      ischemic time, ABO matching, and degree of human leucocyte antigen (HLA)
      mismatching. No significant difference in 5 yr graft survival was found between
      the groups by donor age (p = 0.604) and by donor age compared with recipient age
      (p = 0.567). Moreover, no significant differences in the incidence of primary non
      function and HAT after transplantation were found between the groups by donor age
      and by donor age compared with recipient age. Older donors were more likely to be
      women and to have antibodies to CMV, as well as to have died by cerebrovascular
      causes. Race, body weight, height of both recipients and donors, total or warm
      ischemic time of grafts, ABO matching, and degree of HLA mismatching were not
      significantly different between the groups. We conclude from this study that
      advanced donor age is not a contraindication to liver transplantation if careful
      assessment of donors is made on a case-by-case basis. There is a need to maintain
      an open mind with regard to the use of livers from older donors due to the
      current situation of serious organ shortages.

PMID- 10946777
TI  - Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric
      renal allografts from hepatitis C virus seropositive donors.
AB  - INTRODUCTION: The purposes of this study were: 1) to analyze the early results of
      cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+
      ) or hepatitis C virus seronegative (HCV-) donors into HCV + recipients; and 2)
      to determine whether HCV+ patients with end-stage renal disease (ESRD) might
      benefit from receiving renal allografts from HCV + donors. METHODS: From January
      1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric
      renal transplants. The data were reviewed retrospectively. Nineteen of the renal
      transplants were performed with allografts obtained from 15 HCV + donors and 10
      with allografts obtained from 10 HCV- donors. The median follow-up was 16.2
      months, with an average of 15.4+/-2 months. RESULTS: Recipients of HCV + renal
      allografts had shorter waiting times for transplantation. On average, patients
      who received a kidney from HCV + donors were transplanted 9+/-3 months after
      being placed on the transplant list, compared to 29+/-3 months for patients who
      received a kidney from a HCV- donor. Shorter waiting times were noted in every
      blood type group. There were no significant differences in rejection episodes,
      infectious complications, renal function, liver function, graft survival, or
      patient survival. CONCLUSIONS: The use of renal allografts from HCV + donors for
      HCV + recipients shortens the waiting time for these patients, with no short-term
      differences in renal and liver function, graft loss, or patient survival.

PMID- 10946778
TI  - The use of contaminated donor organs in transplantation.
AB  - INTRODUCTION: Organ transplantation has become an accepted means of treating end
      stage organ disease in recent years with acceptable patient and graft survival.
      Transplant recipients have an increased risk of infectious complications due to
      multiple factors including decreased host resistance from chronic end-stage organ
      failure as well as from the immunosuppression required to prevent graft
      rejection. HYPOTHESIS: Therefore, the use of contaminated allografts could result
      in life-threatening infections in organ recipients. METHOD: In this study,
      transplant patients receiving organs from donors with positive blood or urine
      cultures, from 1993 to 1997, were retrospectively reviewed. RESULTS: There was a
      total of 599 organ donors in our state. Forty-six (7.5%) had positive blood
      cultures and 25 (4.5%) had positive urine cultures. A total of 179 patients
      received organs from these contaminated donors, 36 of which were transplanted at
      our center. In this group, there were 16 kidney, 9 liver, and 11 heart
      transplants. Both donors and recipients received prophylactic broad-spectrum
      antibiotics, which were adjusted based on culture and sensitivity results. The
      most common organisms isolated from the blood were staphylococci followed by
      streptococci and Gram-negative organisms. Three of the 9 liver transplant
      patients in the series died with a mortality of 33%. Two of the 3 patients who
      died had sepsis but the responsible organisms were different from those recovered
      from the donor. The rest (66%) did well and have acceptable liver function. None
      of the 16 renal transplant recipients developed an infection and all survived.
      One patient developed acute irreversible rejection requiring transplant
      nephrectomy. There was one death in the heart transplant group resulting in a
      mortality of 9%. This death was not attributed to infectious processes. Three of
      11 heart transplant patients grew organisms in the post-operative period that
      were similar to those found in the corresponding donors. However, no patient
      suffered significant morbidity or mortality from these infections and all
      recovered. The recipients of contaminated organs had levels of organ function
      similar to those of randomly chosen recipients of non-contaminated organs, and
      both groups had similar lengths of hospital stay. CONCLUSION: Only 3 of 36 organ
      recipients had infections caused by organisms found in the contaminated donor
      organs for a rate of 8%. Contaminated donor organs seem to fare as well as non
      contaminated donor organs and there was no increase in morbidity or mortality.
      Contamination of organs should not be an absolute contraindication to the use of
      these organs in transplantation.

PMID- 10946779
TI  - Characteristics of infectious complications associated with mortality after solid
      organ transplantation.
AB  - Infection remains a common source of morbidity and mortality after solid organ
      transplantation. The purpose of this study was to characterize the continuously
      changing patterns of post-transplantation infections, analyze early post
      transplantation infections, and evaluate characteristics associated with
      mortality. A secondary analysis was performed on prospectively collected data for
      all episodes of infection occurring between 10 December 1996 and 28 October 1998
      on the surgery services at a university medical center. Post-transplantation
      infections were compared with those in non-transplantation patients randomly
      matched by severity of illness. Further analysis was performed on post
      transplantation infections occurring during the admission of transplantation
      compared with those in subsequent admissions. To evaluate factors associated with
      mortality, episodes occurring in survivors and non-survivors were compared. The
      results demonstrated that infections in transplantation recipients (n = 303) were
      associated with a younger age and had significantly lower white blood cell counts
      (WBC) compared with non-transplantation patients. There was no difference in
      mortality (15.5 vs. 16.5%, p = 0.74). Post-transplantation infectious
      complications during the initial hospitalization (n = 105) occurred at 38+/-6
      compared with 695+/-66 d (p<0.0001) after transplantation and were associated
      with a longer length of stay (LOS) and increased mortality (30.5 vs. 7.6%,
      p<0.0001) compared with those occurring in subsequent admissions (n = 198).
      Although multiple characteristics of post-transplantation infections were
      associated with mortality, only the Acute Physiology and Chronic Health
      Evaluation (APACHE) II score was an independent predictor of mortality. Post
      transplantation infections remain a significant source of morbidity and
      mortality. The leukocyte response to infection was suppressed in the
      transplantation population. Post-transplantation infections which occur during
      the admission for transplantation have a markedly increased mortality.

PMID- 10946781
TI  - Analysis of a single-center experience with mycophenolate mofetil based
      immunosuppression in renal transplantation.
AB  - PURPOSE: Acute rejection continues to be a major clinical issue in renal
      transplantation. Three large multicenter trials have demonstrated a 50% decline
      in biopsy-proven rejection when mycophenolate mofetil (MMF) was given to renal
      transplant recipients with corticosteroids and cyclosporine. The purpose of this
      study was to compare the 6-month outcome of renal transplant recipients using MMF
      and non-MMF based immunosuppression protocols over a 4-year period at a single
      center. METHODS: This retrospective study analyzed three patient groups defined
      by their immunosuppression protocol. The first group included patients who
      received a quadruple immunosuppression regimen of anti-lymphocyte induction
      (ATG), cyclosporine (CYA), azathioprine (AZA), and corticosteroids (CCS), and
      were transplanted between October 1993 and May 1995 (AZA group). The second group
      included patients who received a triple immunosuppression regimen of CYA, MMF,
      and CCS, and were transplanted between June 1995 and May 1996 (MMF group). The
      third group included patients who were transplanted between January 1997 and
      December 1997, and received an immunosuppression regimen of CYA and MMF with a
      reduced CCS dosing schema (reduced steroid group (RST)). Data were collected from
      a retrospective review of inpatient and outpatient clinical records. RESULTS: A
      total of 325 patients were included in the study (106 AZA, 106 MMF, 113 RST). The
      demographic characteristics of the three groups were similar; however, the mean
      donor age for the AZA group was 40+/-15.1 years versus 33+/-14.1 years and 34+/
      13.1 years for the MMF and RST groups, respectively (p<0.043). The incidence of
      acute, biopsy-proven rejection at 6 months was significantly less in the MMF
      group when compared with the AZA group [16 (15.1%) versus 35 (33%) patients, p =
      0.002]. However, the incidence of acute, biopsy-proven rejection in the RST group
      (35 patients, 31%) was similar to that of the AZA group. Kaplan-Meier estimates
      for the cumulative incidence of acute rejection demonstrated a significant
      difference between the MMF group and the other two groups (p = 0.0059). The AZA
      group had more severe rejection as demonstrated by the more frequent use of
      antilymphocyte therapy for rejection treatment (68.4% episodes) compared with the
      MMF (38.9%) and RST (47.6%) groups. After 6 months of follow-up, 11 patients had
      lost their grafts (8, AZA; 1, MMF; 2, RST). One patient died in each of the AZA
      and RST groups due to hemorrhage and a pulmonary embolus, respectively. Four AZA
      patients were diagnosed with a malignancy (three post-transplant
      lymphoproliferative disorder, one squamous skin cell carcinoma) compared with 2
      MMF patients (prostate cancer, basal skin cell carcinoma) and no RST patients.
      Herpes zoster was the only infection that occurred more frequently in the MMF
      group (p = 0.03). No other differences in infection rates were noted among the
      three groups. The initial length of hospital stay declined significantly over the
      4-year study period [11+/-4.3 d (AZA), 7.0+/-4.0 d (MMF), 6.2+/-3.3 d (RST),
      p<0.001]. Total number of hospital days for the first 6 months also followed a
      similar declining pattern. Despite using intravenous cyclosporine immediately
      post-transplant in the MMF and RST groups, the incidence of delayed graft
      function was similar among the three groups. Average serum creatinine at 1 month
      was significantly lower in the MMF group (p = 0.008), but no difference was noted
      at 3 and 6 months when compared with the AZA and RST groups. CONCLUSION: This
      retrospective analysis indicates that MMF is an effective immunosuppressant.
      Decreased length of stay and less steroid resistant rejections with MMF is
      favorable for decreased hospital costs. However, the rebound in rejection rate
      with the RST group suggests that further study is needed to define the optimal
      use of this agent in combination with others to maximize effectiveness and
      minimize negative side effects.

PMID- 10946780
TI  - A comparison of daclizumab to ATGAM induction in simultaneous pancreas-kidney
      transplant recipients on triple maintenance immunosuppression.
AB  - Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab
      directed against the alpha chain of the interleukin-2 receptor (IL2R). Inhibiting
      the amplification of the immune response by blocking IL2R can reduce the
      frequency of acute rejection without the attendant risk of infection. The purpose
      of this retrospective study was to compare DAC to antithymocyte (ATGAM) induction
      in 24 simultaneous pancreas-kidney (SPK) transplants performed between September
      1995 and September 1998. The primary endpoints were the incidence within 6 months
      posttransplant of: 1) biopsy-proven acute rejection; and 2) infection. The two
      groups (DAC, n = 12; ATGAM, n = 12) were matched on age, race, ESRD, number of
      HLA mismatches, PRA level, and cold ischemia time. DAC (1 mg/kg) was given on the
      day of transplant, then every other week (a total of five doses); ATGAM (15
      mg/kg) was given on post-transplant day 1, then daily for 7-10 d.
      Immunosuppressive therapy consisted of cyclosporine (Neoral 8-10 mg/kg/d) or
      Prograf (0.16-0.2 mg/kg/d), mycophenolate mofetil (Cell- 2-3 g/d) and steroids.
      Of the 12 DAC patients, 3 patients (25%) had biopsy-proven acute rejection versus
      8/12 (67%) of the ATGAM patients. The time to acute rejection was significantly
      different by group (DAC = 110 d; AT-GAM = 26 d). There was a reduction in the
      number of patients receiving antilymphocyte drugs for moderate to severe
      rejection (DAC = 2/12; ATGAM = 4/12), with 2 of the 4 ATGAM patients experiencing
      more than two episodes of biopsy-proven rejection. There was an increase in
      infection by group (DAC = 4/12; ATGAM = 7/12): total of three septic infections
      occurred in the ATGAM group opposed to none in the DAC group. Patient, pancreas,
      kidney 6-month survival rates were 100% for both groups. We conclude that DAC
      induction coupled with triple immunosuppressive therapy reduces the incidence of
      rejection in SPK transplant patients. The time to acute rejection was prolonged
      in the DAC group compared with the ATGAM group without the attendant risks of
      rejection.

PMID- 10946782
TI  - Mycophenolate mofetil, with cyclosporine and prednisone, reduces early rejection
      while allowing the use of less antilymphocytic agent induction and cyclosporine
      in renal recipients with delayed graft function.
AB  - Antilymphocytic agent induction (ALAI), with antithymocyte globulin or monoclonal
      antibody, is generally used in renal transplantation (TX) to spare renal
      allografts with poor initial function from the toxic effects of cyclosporine
      (CsA) and/or to augment immunosuppression (IS) in the patient at a high risk for
      early rejection. ALAI, unfortunately, increases the cost of TX and the risk to
      the patient, having been associated with many adverse side effects. An IS
      protocol, which results in a low incidence of early rejection while using less
      CsA and ALAI, is a worthwhile goal. We compare our experience with mycophenolate
      mofetil (MMF), CsA, and prednisone (MMFCP; n = 62) to our azathioprine (AZA),
      CsA, and prednisone (AZACP; n = 50) triple-drug IS, with and without ALAI. The
      patient characteristics for age, race, first TX, cadaveric donor, pediatric
      recipient, and dialysis in the first post-op week (DGF) were not different for
      the MMFCP versus AZACP groups. There were more females in the MMFCP group (51.6%
      versus 30.0%, p = 0.022). We report that rejection-free survival at 6 months
      (RF6) was better in the MMFCP versus AZACP group (83.9% versus 60.0%, p = 0.005).
      Less ALAI and CsA were used in the MMFCP patients. At 1 year, actuarial graft
      survival was 91.9% in the MMFCP group and 81.9% in the AZACP group (p = 0.116).
      Actuarial 1-year patient survivals were not different in the two patient groups.
      In the sub-population of patients with DGF, the RF6 in the MMFCP (n = 13) group
      was 92.3% versus 57.1% in the AZACP (n = 14) group (p = 0.041). The reduction in
      early rejection episodes in the patients on MMFCP with DGF was accomplished while
      using half as much ALAI and lower CsA doses and levels. The African-American
      recipient sub-population on MMFCP also demonstrated an improvement in RF6 while
      using less ALAI and CsA (78.6% versus 48.0%, p = 0.022). We conclude that the use
      of MMF-based triple-drug IS results in fewer rejection episodes while allowing
      for lower CsA levels and less ALAI, even in patients with delayed graft function.

PMID- 10946783
TI  - Laparoscopic live donor nephrectomy: pre-operative assessment of technical
      difficulty.
AB  - Laparoscopic live donor nephrectomy decreases disincentives to live kidney
      donation. Thus, many centers are interested in adopting this procedure. However,
      the high stakes involved for both the donor and the recipient, and the technical
      difficulties of the operation, have tempered the enthusiasm of some surgeons.
      Ideally, if early in their series, surgeons could select patients that would be
      the least challenging technically, it would facilitate the dissemination of this
      operation. The purpose of this study is to determine if anatomic or radiologic
      parameters can accurately assess pre-operatively the degree of technical
      difficulty of laparoscopic live donor nephrectomy for any individual patient.
      Abdominal spiral three-dimensional CT scanning was performed prior to
      laparoscopic donor nephrectomy. CT scans were reviewed for six radiographic
      anatomic parameters. Seven clinical anatomic measurements relating to body
      habitus were recorded upon induction anesthesia at the time of surgery.
      Demographic data for gender, age, race, weight, height, and smoking history were
      collected. Following laparoscopic live donor nephrectomy, the following six
      component parts of the operation were graded on a scale of 1-4 (1 = easy, 4 =
      very difficult) for technical difficulty: a) mobilization of the colon; b)
      mobilization of the upper pole; c) dissection of the renal vein; d) dissection of
      the renal artery; e) division of the adrenal vein; and f) dissection of the
      ureter. Also, operative time, estimated blood loss, and intra-operative fluid
      requirements were recorded as surrogate markers of operative difficulty. Forty
      one patients were included in the study. Laparoscopic donor nephrectomy was
      successfully completed in all cases. The sum of the difficulty scores was 9.9+/
      3.1 (mean) (range, 6-18). No anatomic, demographic, or radiologic parameters were
      predictive of the total operative difficulty score. Of the surrogate markers,
      only operative time correlated with total difficulty score (R = 0.47, p = 0.003).
      Donor weight and abdominal girth correlated with operative time (R = 0.50, p =
      0.002; R = 0.38, p = 0.019) but not with total difficulty score (R = 0.10, p =
      0.51; R = -0.02, p = 0.90, respectively). When the easiest cases and the hardest
      cases (< or = 25th percentile and > or =75th percentile total difficulty score,
      respectively) were segregated out, again no anatomic, demographic, or radiologic
      parameters were predictive of operative technical difficulty. In conclusion,
      laparoscopic live donor nephrectomy technical difficulty could not be predicted
      by body habitus from the variables examined in this study. Hence, it was equally
      likely that performing laparoscopic live donor nephrectomy using a heavy donor
      would be technically easy, as using a thin donor would be difficult. Although, in
      general, operative time increased with donor size and weight, it appears that
      laparoscopic live donor nephrectomy operative technical difficulty is dependent
      upon such factors as amount of laparoscopic working space, quality of tissue
      planes, and retractability of the colon and mesocolon; factors that, to date, are
      not quantifiable.

PMID- 10946784
TI  - Living kidney donation: recovery and return to activities of daily living.
AB  - To determine donor nephrectomy outcomes, a one page 20-item survey of 42 cases
      was reviewed, including demographics, intervals to normal activities (e.g.,
      driving a car, returning to work), and an open inquiry about the donation
      process. Hospital records were also reviewed. Nephrectomy under general
      anesthesia was through an anterior flank, extra-retroperitoneal approach with
      postoperative epidural pain control. Early self-care, progressive ambulation, and
      prescriptive pulmonary care were undertaken to facilitate recovery. Length of
      stay averaged 3.4 (range 2-8) d, and mean hospitalization charge was $15 169
      (range $10 733-S29 579). Thirty-four donors were employed outside the home; 18
      (53%) returned to work within 4 wk, and the average duration away from work was
      4.6 wk (range 6 d 10 wk). Within 2 wk, 25 (59%) were driving an automobile. Usual
      activities of daily living were fully performed by all donors at a mean of 4.8 wk
      (minimum 5 d). Forty respondents would donate again, and one might; one did not
      respond to this question. None reported intermediate or long-term disabilities
      and all reported return to their pre-donation level of activity. With the
      anterior extra-retroperitoneal nephrectomy, most donors were out of the hospital
      within 4 d, were driving within 2 wk, and returned to gainful employment within 4
      wk. Living kidney donation, as viewed by the donors, was a positive experience,
      which appeared to disrupt their lives minimally.

PMID- 10946785
TI  - Early nutrition and the development of immune function in the neonate.
AB  - The present review will concentrate on the development of the gut-associated
      lymphoid tissue and the role of early nutrition in promoting immune function. The
      intestine is the largest immune organ in the body, and as such is the location
      for the majority of lymphocytes and other immune effector cells. The intestine is
      exposed to vast quantities of dietary and microbial antigens, and is the most
      common portal of entry for pathogens, some of which are potentially lethal. The
      development of normal immune function of the intestine is therefore vital for
      survival, and is dependent on appropriate antigen exposure and processing, and
      also an intact intestinal barrier. In early life innate mechanisms of defence are
      probably more important than active or adaptive mechanisms in responding to an
      infectious challenge, since the healthy neonate is immunologically naive (has not
      seen antigen) and has not acquired immunological memory. During this period
      maternal colostrum and milk can significantly augment resistance to enteric
      infections. The mechanisms of enhancing disease resistance are thought to be
      passive, involving a direct supply of anti-microbial factors, and active, by
      promoting the development of specific immune function. A tolerance response to
      dietary and non-invasive antigens is generally induced in the gut. However, it
      must also be able to mount an adequate immune response to ensure clearance of
      foreign antigens. It is now recognized that regulation of tolerance and active
      immune responses is critical to health, and failure to regulate these responses
      can lead to recurrent infections, inflammatory diseases and allergies. The
      education of the immune system in early life is thought to be critical in
      minimizing the occurrence of these immune-based disorders. During this phase of
      development maternal milk provides signals to the immune system that generate
      appropriate response and memory. One factor that has been proposed to contribute
      to the increase in the incidence of immune-based disorders, e.g. atopic diseases
      in Western countries, is thought to be the increased prevalence of formula
      feeding.

PMID- 10946786
TI  - Assessment of individual fatty acid intake.
AB  - Dietary assessment of individual fatty acid intake is difficult due to a number
      of limitations. Information regarding the type, quantity and brand-name of fat
      used in cooking and at the table is required. In addition, margarine
      manufacturers may change the component oils used for reasons of cost, which
      changes the fatty acid composition of their products from season-to-season.
      Independent markers of fatty acid intake are required, therefore, to compensate
      for these limitations. Adipose tissue concentrations have been used as a measure
      of habitual intake of fatty acid groups and individual fatty acids in numerous
      studies. Saturated (SFA) and monounsaturated fatty acids (MUFA) are generally
      poorly correlated with adipose tissue concentrations, which can be explained
      partly by endogenous synthesis. In general, adipose tissue concentrations of
      exogenously-produced fatty acids (n-3 and n-6 polyunsaturated fatty acids (PUFA))
      are well correlated with estimates of habitual intake. Correlations between
      dietary trans unsaturated fatty acids (TUFA) and adipose tissue concentrations
      vary between countries, which may be due to differences in dietary sources.
      Correlations may be affected by differences in bioavailability or selective
      retention of fatty acids in certain tissue lipids.

PMID- 10946787
TI  - Interactions between physical activity and diet in the regulation of body weight.
AB  - The increasing worldwide prevalence of obesity suggests that there is a chronic
      positive energy balance. This situation implies poor coupling between energy
      intake and energy expenditure, but the contribution of each of these factors
      remains unclear. Epidemiological data suggests that physical activity has a role
      in the prevention of weight gain, although there is little evidence that it has a
      beneficial role in weight loss. High-fat diets have also been implicated,
      evidence from a variety of sources suggests that diets high in fat undermine
      appetite regulatory mechanisms. There has been much research to investigate the
      coupling between energy expenditure and energy intake in the short term in an
      attempt to elucidate some of the mechanisms involved. However, mechanisms
      regulating appetite are very complex, and it is currently unclear at which points
      physical activity and diet may have an influence.

PMID- 10946788
TI  - Energy expenditure in disease: time to revisit?
AB  - Knowledge of energy expenditure is especially important in disease, and may in
      fact help in the understanding of the pathophysiology of wasting associated with
      disease. Energy requirements in a clinical setting are often 'prescribed' by
      health professionals, either directly through enteral or parenteral feeding, or
      perhaps controlled through a hospital diet. Studies initially suggested an
      increase in energy expenditure, and thus energy requirements, as a direct result
      of an increase in basal metabolic rate often seen in disease. However, many
      problems exist in the measurement of BMR in a disease situation, due to the
      effects of drugs, clinical practice, feeding or possibly anxiety either as a
      cause of the disease or the measurement itself. These problems could in
      themselves contribute to the rise in metabolism seen in disease. More recently,
      however, with the use of tracer techniques such as doubly-labelled water and the
      bicarbonate-urea method, more accurate estimates of energy expenditure, and thus
      energy requirements, have been made. Some such measurements have in fact shown
      that even with an elevated BMR, free-living total energy expenditure can in fact
      be reduced in many disease situations, suggesting a reduced rather than an
      increased energy requirement. The present review investigates measurements of
      total energy expenditure in disease to explore the hypothesis that energy
      expenditure in disease, even with an elevated BMR, can in fact be reduced due to
      a concurrent reduction in physical activity.

PMID- 10946789
TI  - New perspectives on the use of tropical plants to improve ruminant nutrition.
AB  - Inadequate nutrition is the main cause of low productivity by ruminants in sub
      Saharan Africa. The primary feed resources in the region include natural pasture
      and crop residues that have tough texture, poor digestibility and are deficient
      in nutrients. These deficiencies can be corrected by supplementation with high
      density feeds such as oilseed cakes and proteins of animal origin. However,
      protein sources such as oilseed cakes are beyond the economic reach of most
      farmers, while the incidence of bovine spongiform encephalopathy in Western
      intensive animal production may be thought to argue against the use of animal
      proteins. Local tree legumes have been investigated as potential supplements for
      ruminants because of their beneficial effect of increasing metabolizable energy
      intake, N intake and feed efficiency, and improving animal performance. However,
      our work has suggested that some plant materials may have a nutritional value
      beyond simply their nutrient content, i.e. as rumen-manipulating agents. The
      foliage of some tree legumes has been shown to be selectively toxic to rumen
      protozoa. Rumen protozoa ingest and digest bacteria and fungi, degrading their
      cellular protein to NH3. Microbial protein turnover due to protozoal predation in
      the rumen may result in the net microbial protein outflow being less than half
      the total protein synthesized. Results from in vivo experiments have clearly
      shown that duodenal flow of both undegraded dietary and bacterial protein is
      generally increased by defaunation. However, no practical method has been
      developed to date to eliminate protozoa. Anti-protozoal plants may be promising,
      safe, natural defaunating agents.

PMID- 10946790
TI  - Kill and cure: dietary augmentation of immune defences against colon cancer.
AB  - At its most fundamental, cancer is a genetic disease resulting from inherited or
      acquired mutations in tumour suppressor genes and proto-oncogenes. Environmental
      factors, including ingested food components, interact with genetic inheritance to
      determine individual cancer risk. There is growing evidence that the immune
      system exerts selective pressure during neoplastic development. Tumour cells that
      evade this immunosurveillance because they are non-antigenic or because they
      defend themselves successfully against immune attack have a survival advantage.
      Effective chemopreventative agents will include dietary components that enhance
      the immune system's ability to identify transformed cells and to target them for
      apoptosis.

PMID- 10946791
TI  - Nutritional aspects and possible pathological mechanisms of
      hyperhomocysteinaemia: an independent risk factor for vascular disease.
AB  - Numerous case-control and prospective studies have identified elevated plasma
      homocysteine as a strong independent risk factor for cerebovascular,
      cardiovascular and peripheral vascular disease. Homocysteine is formed as a
      result of the breakdown of the dietary amino acid methionine. Once formed,
      homocysteine is either remethylated to methionine, or undergoes a trans
      sulfuration reaction to form cysteine. The re-methylation of homocysteine to
      methionine is dependent on three B-vitamins, i.e. riboflavin, vitamin B12 and
      folate. The second pathway of homocysteine metabolism is the trans-sulfuration
      pathway which requires both vitamin B6 and riboflavin for its activity. Thus, up
      to four B-vitamins are required for intracellular homocysteine metabolism. Many
      studies have noted strong inverse relationships between homocysteine levels and
      the status of both vitamin B12 and folate. However, the relationship between
      vitamin B6 status and homocysteine is still uncertain. Similarly, numerous
      intervention studies have demonstrated effective lowering of homocysteine levels
      as a result of folate and vitamin B12 supplementation, while the homocysteine
      lowering ability of vitamin B6 is unclear. Even though riboflavin plays a crucial
      role in both the trans-sulfuration and remethylation pathways of homocysteine
      metabolism, the relationship between riboflavin status and homocysteine levels
      has not been investigated. The exact mechanism that explains the vascular
      toxicity of elevated homocysteine levels is unknown at present, studies indicate
      that it is both atherogenic and thrombogenic. To date, no randomized clinical
      trial has demonstrated that lowering of homocysteine levels is beneficial in
      terms of reducing the prevalence of vascular disease. It is probable, however,
      that optimal B-vitamin status is important in the prevention of vascular disease.

PMID- 10946792
TI  - Sensory control of energy density at different life stages.
AB  - Taste preferences, food choices and eating habits all change with age. The
      transition from childhood to adolescence and adult life is associated with
      reduced sweet taste preferences, lower sugars consumption and reduced energy
      density of the diet. Ageing is associated with elevated acceptance of bitter
      tastes, elevated preferences for vegetables and salad greens, and increased
      consumption of whole grains, vegetables and fruit. The age-associated drop in
      energy intakes is achieved through a reduction in the weight and volume of food
      consumed, as well as a reduction in the overall energy density of the diet.
      Energy density drops from a peak of 5 kJ (1.2 kcal)/g in adolescence and early
      adult life to a low of 3.1 kJ (0.75 kcal)/g for adult women aged 45-54 years.
      Older adults, particularly women, consume less fat and saturated fat and more
      fibre and vitamin C, suggesting a shift in consumption from snacks, sweets and
      desserts towards grains, vegetables and fruit. These changes in food preferences
      and eating habits are associated, on a population level, with a decline in
      preferences for sweet taste and with increased acceptance of bitter tastes. At
      present there are no data to show a causal relationship between age-related
      changes in sensory function and the selection of a more bulky energy-dilute diet.
      However, it is a plausible hypothesis that sensory factors mediate adjustments in
      energy density of foods at different life stages.

PMID- 10946793
TI  - Long-term physiological and economic consequences of growth retardation in
      children and adolescents.
AB  - The application of a lifespan perspective in human biology in recent years has
      shown that a number of early environmental factors influencing human growth and
      development have long-term biological or psycho-social consequences. Human growth
      is characterized by prolonged infancy, an extended childhood phase and high rates
      of growth during the adolescent growth spurt. It is unlikely that these
      characteristics would have evolved without having advantages, and curtailments
      have the potential for disadvantage. The present paper examines the evidence for
      long-term physiological and economic consequences of growth retardation in
      children and adolescents. The emphasis is the biological and economic imperatives
      of survival, subsistence, reproduction and production rather than aspects of
      metabolic competence. Many of the consequences of growth retardation are
      determined by the direct effect on body size, but many other consequences arise
      from the conditions that cause the growth retardation. Catch up of retarded
      growth can occur, but does not usually do so because of the continued presence of
      the retarding agents. Basal metabolism and physical work capacity are usually
      commensurate with the size of the individual; mechanical efficiency of physical
      work is unchanged, but falls in activity levels may occur along with a reduction
      in the pace of activity. Growth retardation in childhood is associated with a
      higher disease and mortality risk in adulthood, with decreased productivity and
      employment and promotion prospects. Studies are showing that relative deprivation
      and the accumulation of socially patterned exposures are important in some
      societies. Height and growth retardation have proved invaluable in reflecting
      these factors, but the next generation of studies may require more discriminating
      indices.

PMID- 10946794
TI  - Interactions of perturbations in intrauterine growth and growth during childhood
      on the risk of adult-onset disease.
AB  - The 'fetal origins' hypothesis (Barker, 1995) would predict that the rising
      epidemic of diabetes and CHD in India would be due to poor intrauterine growth of
      the Indian babies. While this explanation may be valid to an extent, the higher
      prevalence of these disorders in urban compared with rural India (where birth
      weights are lower) would suggest a significant role for postnatal factors. In a
      cohort of 477 children born in the King Edward Memorial Hospital, Pune, we found
      that at 8 years of age current obesity strongly predicted insulin resistance.
      When this effect was allowed for, low birth weight was significantly associated
      with insulin-resistance variables and other cardiovascular risk factors. Children
      who were born small but had grown heavy (or tall) were the most insulin resistant
      and had the highest levels of cardiovascular risk factors. Accelerated growth in
      relation to mid parental height was similarly predictive. Poor intrauterine
      growth also predicted higher central adiposity at 8 years of age. We have also
      studied maternal nutrition and fetal growth in six villages near Pune. A newborn
      Indian baby is small (2650 g, SD score (SDS) -1.6 compared with an average white
      Caucasian baby born in the UK) and 'thin' (ponderal index 2.45 kg/m3, SDS -1.2),
      but has preserved its subcutaneous fat (subscapular skinfold thickness SDS -0.6).
      The thinness of the Indian babies is due to poor muscle and small abdominal
      viscera. We have proposed this composition as the 'thrifty phenotype' (Hales &
      Barker, 1992) of Indian babies. Maternal size and intake of certain food groups
      during pregnancy were important determinants of the baby's phenotype. Thus, the
      small Indian babies are programmed to deposit fat from their intrauterine life.
      Exaggeration of this tendency in later life is associated with insulin-resistance
      syndrome. Control of the insulin-resistance epidemic in India might depend on
      improved intrauterine development and prevention of childhood obesity.

PMID- 10946795
TI  - Nutritional and other influences in childhood as predictors of adult obesity.
AB  - It has been proposed that there are critical periods during childhood that
      influence the development of obesity, including gestation and early infancy, the
      period of adiposity rebound that occurs between ages 5 and 7 years, and
      adolescence. Despite an extensive literature, there is to date only modest
      evidence for most of the factors such as nutrition, physical activity and other
      behavioural factors that are suspected as playing a role in the development of
      obesity. A recent review of this evidence (Parsons et al. 1999) showed, however,
      a consistent relationship between socio-economic status (SES) of origin and adult
      obesity, whereby those from lower SES backgrounds were fatter subsequently in
      adulthood. This association appeared to apply to both men and women, a finding
      that contrasts with the trends observed in cross-sectional studies, of an
      association with SES for women only. There are several potential explanations for
      the SES of origin-adult obesity relationship. SES of origin may be confounded by
      parental body size; studies to date provide insufficient evidence of an
      independent association with SES after allowing for parental body size.
      Alternatively, environment in early life (for which SES of origin is a proxy
      measure) may have a long-term impact on obesity later in adulthood, through one
      or more of several processes. Three major potential explanations can be
      identified: (1) nutrition in infancy and childhood, either over- or
      undenutrition, followed subsequently by overnutrition; (2) psychological factors,
      possibly involving emotional deprivation in childhood; (3) cultural or social
      norms regarding dietary restraint and attitudes to fatness that may be acquired
      during childhood.

PMID- 10946796
TI  - Food allergy and nutrition in early life: implications for later health.
AB  - Allergic diseases are a common cause of illness in most industrialized countries.
      Diet during early childhood is an important determinant of the development of
      allergy, particularly in high-risk infants who have a parental history of atopy.
      Maternal avoidance of highly-allergenic foods during pregnancy and lactation,
      prolonged exclusive breast-feeding, the use of a hydrolysed milk formula, and
      delayed introduction of dairy products, eggs, fish, nuts and soybean are
      associated with a lower incidence of allergic symptoms and signs. These
      beneficial effects are observed for as long as 18 years of age. Similarly,
      nutrition and physical growth are important factors that influence
      immunocompetence and morbidity due to infections. Small-for-gestational age low
      birth-weight infants show prolonged impairment of cell-mediated immunity,
      antibody responses and phagocyte function. Recent studies indicate the beneficial
      effect of moderate amounts of Zn given in the first 6 months of life. Thus, diet
      and nutrition in early life are crucial for the development of allergic and
      infectious disease throughout childhood and into adulthood.

PMID- 10946797
TI  - Measurement of dietary intake in children.
AB  - When children and adolescents are the target population in dietary surveys many
      different respondent and observer considerations surface. The cognitive abilities
      required to self-report food intake include an adequately developed concept of
      time, a good memory and attention span, and a knowledge of the names of foods.
      From the age of 8 years there is a rapid increase in the ability of children to
      self-report food intake. However, while cognitive abilities should be fully
      developed by adolescence, issues of motivation and body image may hinder
      willingness to report. Ten validation studies of energy intake data have
      demonstrated that mis-reporting, usually in the direction of under-reporting, is
      likely. Patterns of under-reporting vary with age, and are influenced by weight
      status and the dietary survey method used. Furthermore, evidence for the
      existence of subject-specific responding in dietary assessment challenges the
      assumption that repeated measurements of dietary intake will eventually obtain
      valid data. Unfortunately, the ability to detect mis-reporters, by comparison
      with presumed energy requirements, is limited unless detailed activity
      information is available to allow the energy intake of each subject to be
      evaluated individually. In addition, high variability in nutrient intakes implies
      that, if intakes are valid, prolonged dietary recording will be required to rank
      children correctly for distribution analysis. Future research should focus on
      refining dietary survey methods to make them more sensitive to different ages and
      cognitive abilities. The development of improved techniques for identification of
      mis-reporters and investigation of the issue of differential reporting of foods
      should also be given priority.

PMID- 10946798
TI  - Changing eating and physical activity patterns of US children.
AB  - The number of US children who are overweight has more than doubled over the last
      decade. This change has broadened the focus of dietary guidance for children to
      address nutrient overconsumption and physical activity patterns. Total fat
      consumption expressed as a percentage of energy intake has decreased among US
      children. However, this decrease is largely the result of increased total energy
      intake in the form of carbohydrates and not necessarily due to decreased fat
      consumption. The majority of children aged 5-17 years are not meeting
      recommendations for Ca intakes. Much of this deficit is attributed to changing
      beverage consumption patterns, characterized by declining milk intakes and
      substantial increases in soft-drink consumption. On average, US children are not
      eating the recommended amounts of fruits and vegetables. US adolescents become
      less active as they get older, and one-quarter of all US children watch > or = 4
      h television each day, which is positively associated with increased BMI and
      skinfold thickness. There is an urgent need in the USA for effective prevention
      strategies aimed at helping children grow up with healthful eating and physical
      activity habits to achieve optimal health.

PMID- 10946799
TI  - The growing years and prevention of osteoporosis in later life.
AB  - Ca is the major mineral in bone, and 99% of the Ca in the body resides in the
      skeleton. Skeletal mass is a determinant of risk of fracture in childhood as well
      as adulthood. Over 40% of adult peak bone mass is acquired during adolescence.
      This period is when lifestyle choices, including ensuring adequate dietary Ca,
      regular weight-bearing exercise and avoiding hormonal insufficiency, are
      especially important. Current Ca intakes for adolescent females are woefully
      inadequate.

PMID- 10946800
TI  - Childhood nutrition and poverty.
AB  - One in three children in Britain lives in poverty (households whose income was
      less than 50% average earnings). Low income is associated with poor nutrition at
      all stages of life, from lower rates of breast-feeding to higher intakes of
      saturated fatty acids and lower intakes of antioxidant nutrients. Moreover, there
      is increasing evidence that poor nutrition in childhood is associated with both
      short-term and long-term adverse consequences such as poorer immune status,
      higher caries rates and poorer cognitive function and learning ability. These
      problems arise primarily because parents do not have enough money to spend on
      food, not because money is being spent unwisely. Policy options to improve the
      dietary health of poor children include: giving more money to the parents by
      increasing Income Support (social security) payments, providing food stamps or
      vouchers, and using food budget standards to inform the levels of income needed
      to purchase an adequate diet; feeding children directly at school (not only at
      lunchtime but also at breakfast or homework clubs), by providing free fruit at
      school, and by increasing entitlement to free food amongst children living in
      households with low incomes; improving access to a healthy and affordable diet by
      first identifying 'food deserts' and then considering with retailers and local
      planners how best to provide food in an economical and sustainable way. The value
      of using food budget standards is illustrated with data relating expenditure on
      food to growth in children from 'at-risk' families (on low income, overcrowded,
      headed by a lone parent or with four or more children under 16 years of age)
      living in a poor area in London. Lower levels of expenditure are strongly
      associated with poorer growth and health, independent of factors such as birth
      weight, mother's height, or risk score. The present paper provides evidence that
      supports the need to review Government legislation in light of nutrition-related
      inequalities in the health of children.

PMID- 10946801
TI  - Secular trends in growth.
AB  - Since the 19th century there have been clearly documented secular trends to
      increasing adult height in most European countries, with current rates of 10-30
      mm/decade. Over the same period menarcheal age has also fallen steeply, but has
      now stabilized at approximately 13 years and may be rising again. Height trends
      tend to be greater in childhood than in adulthood due to the associated advance
      in maturation, but no trends are apparent before the age of 2 years. In
      particular, birth-weight trends are small and different in shape from height
      trends. The adult height trend matches that at age 2 years, so that the increment
      in adult height has already been achieved by age 2 years. To try to identify
      factors relating to the secular trend, increased height gain in late infancy is
      hypothesized to be equivalent to a reduction in stunting, and stunting is thought
      to be caused by impaired growth in the long bones of the leg in later infancy.
      Leg growth may be regulated by the expression of growth-hormone receptors on the
      growth plates, which it is hypothesized are susceptible to the interaction
      between concurrent nutrition and the nominal growth rate set during pregnancy.
      The timing of menarche is also likely to be determined by some growth factor
      operating near the time of birth, which also affects later weight, but not
      height.

PMID- 10946802
TI  - The acquisition of obesity: insights from cellular and genetic research.
AB  - The acquisition of increased adipose tissue mass in man occurs during prolonged
      periods of positive energy balance. Normally, energy homeostasis in children and
      adults is regulated strictly and the energy stores are kept within the defined
      age-dependent physiological range. Susceptibility to definitive increases in the
      level of energy balance during times of reduced energy consumption or increased
      energy intake, leading to changes in body composition and/or changes in relative
      body weight, seems to be genetically determined. Although at present much
      information on the regulation of energy homeostasis and related unfavourable
      factors exists from animal studies, knowledge of the regulation of energy balance
      in human subjects is still insufficient. Some evidence on relevant factors
      involved in the regulation of energy balance in man has been obtained from
      epidemiological data, as well as from studies of patients with rare monogenetic
      forms of obesity. In the present article a special focus will be put on the
      regulation of body energy stores at the level of the adipose tissue, with
      emphasis on the regulation of human adipocyte differentiation. In addition to the
      currently intensive scientific interest in the central regulation of energy
      homeostasis in man, there is sufficient evidence to support the idea that the
      acquisition of an increased adipose tissue mass is also dependent on the
      susceptibility of pre-adipocytes to proliferate, to differentiate or to enter
      into apoptosis.

PMID- 10946803
TI  - Assessment of inflammation and nutrition in patients with end-stage renal
      disease.
AB  - Malnutrition commonly occurs in patients with end-stage renal disease (ESRD), and
      hypoalbuminemia is considered the best clinical marker of malnutrition and
      mortality in this population. Recently, it has been recognized that a substantial
      number of patients with ESRD have serologic evidence of an augmented inflammatory
      response and moreover, inflammation may be as or more important than protein
      intake in causing hypoalbuminemia. In addition, the presence of inflammation may
      be a more powerful predictor of mortality than dietary protein intake. The
      presence of inflammation is often subtle and is detected by increased levels of
      the positive acute phase proteins, most notably C-reactive protein. The causes of
      the stimulation of the systemic inflammatory response may include reaction to
      dialyzer membranes, increased production of advanced glycosylated end-products,
      oxidative stress of uremia and overt and occult infections, especially
      unrecognized arteriovenous graft infections. There is a complex relationship
      between inflammation and nutritional status. Inflammation can cause both anorexia
      with protein-calorie malnutrition as well as wasting through mechanisms mediated
      by cytokines. Novel therapies will need to be developed to counter this systemic
      inflammation since it appears to be a major cause of mortality in patients with
      end-stage renal disease.

PMID- 10946804
TI  - Urea: new questions about an ancient solute.
AB  - Urea recycling and counter-current exchange within the renal tubular, vascular
      and interstitial compartments help maintain high levels of this solute in the
      renal medulla, that are crucial for the production of concentrated urine. The
      role of urea in physiological and pathological conditions is still unclear,
      although new information is becoming available. Several urea transporters have
      been identified that mediate facilitated transport of urea across biological
      membranes in the mammalian kidney, in amphibians, and in elasmobranchs. Evidence
      that urea transporters may be expressed in other mammalian organs is also
      beginning to emerge. The mechanisms involved in the regulation of urea transport
      are incompletely understood. In this respect, the structural and functional
      characterization of individual transporters is providing the basis to identify
      specific regulatory factors. Urea can be viewed as a perturbing osmolyte in the
      renal inner medulla, and the mechanisms of adaptation of renal cells to high
      concentration of this destabilizing solute are being investigated. Urea-specific
      signaling pathways have been identified, that could contribute to clarify how
      cells handle urea.

PMID- 10946805
TI  - Diet or dialysis in the elderly? The DODE study: a prospective randomized
      multicenter trial.
AB  - There are no solid data on the real advantage of an early start of dialysis, as
      suggested by the DOQI guidelines. Uremic patients frequently have a poor
      nutritional status. However, we cannot distinguish between the detrimental effect
      on nutrition of too low a residual renal function or too long a period of low
      protein-diet, per se. However, it appears that a very-low-protein diet (VLPD)
      supplemented with essential amino acids and keto-analogs of amino acids, and with
      an adequate quantity of calories, can prevent hypoalbuminemia at the start of
      dialysis and can slow the progression of chronic renal failure. EDTA and USRDS
      data suggest that most patients starting dialysis nowadays are elderly, who also
      have the highest incidence of morbidity and mortality. Moreover, hospitalization
      rate becomes higher after the start of dialysis compared to the pre-dialysis
      period. Can an aminoacid-supplemented VLPD, prolonged beyond the GFR limits
      suggested by DOQI, offer elderly patients better survival and better quality of
      life than dialysis? The answer can only come from a prospective, randomized
      trial, in elderly patients, starting at the GFR values suggested by the NKF-DOQI
      for starting dialysis, comparing outcomes with a vegetarian VLPD supplemented
      with a mixture of keto-analogs of amino acids and essential amino acids, and with
      dialysis.

PMID- 10946806
TI  - Pefloxacin in steroid dependent and resistant idiopathic nephrotic syndrome.
AB  - Children with nephrotic syndrome who are either steroid dependent or resistant
      are difficult to manage. Ten children (age 8-14 years, mean 13.2 years) with
      idiopathic nephrotic syndrome (5 steroid dependent, 5 steroid resistant) formed
      the study group. All of them had received a course of cyclophosphamide at least
      six months previously and were now given pefloxacin in the dose of 200mg to 400mg
      twice daily (mean dose 2-4.6mg/kg/daily) for 4 to 8 weeks. They did not get
      steroid along with pefloxacin. After a mean follow up period of 18 weeks (12-20
      weeks), 7 patients were in remission (2 complete, 5 partial), while 2 patients
      did not show any response; one patient discontinued pefloxacin within 2 weeks of
      start of therapy due to nausea and vomiting. One patient developed arthralgia and
      another discoloration of nails. There was a significant reduction in proteinuria
      after pefloxacin therapy (pre-3.6+/-2.02gm/24h; post 1.9+/-1.8gm/24h, p<0.006),
      and side effects were minimal and reversible. Thus for the subgroup of idiopathic
      nephrotic children who are steroid dependent or resistant and do not respond to a
      course of cyclophosphamide, pefloxacin could be helpful in inducing remission.

PMID- 10946807
TI  - Clinical significance and long-term evolution of minimal change histopathologic
      variants and of IGM nephropathy among Egyptians.
AB  - In children, the most frequent idiopathic nephrotic syndrome is minimal change
      nephrotic syndrome (MCNS). Typically, MCNS shows no abnormalities by light
      microscopy: "nil disease". Beside this classic picture, there are other minor
      light microscopic abnormalities which are considered as MCNS variants. Our 172
      MCNS patients were divided into a nil disease group, two groups of MCNS variants
      (mild mesangial hypercellularity and mild mesangial thickening) and a fourth
      group with normal light microscopy and diffuse IgM deposition (IgM nephropathy
      group). The relation of this fourth group to MCNS is controversial in the
      literature. Age and serum creatinine were significantly different in the four
      histologic groups (P=0.03 for age and 0.047 for serum creatinine). Comparing the
      groups in pairs, it appeared that these significant differences were due to
      significantly higher age and serum creatinine in the mild mesangial
      hypercellularity group than in the IgM nephropathy group (P = 0.02 for age and
      0.01 for serum creatinine). The groups were similar as regards follow-up
      creatinine clearance and early and late steroid response. We concluded that mild
      mesangial hypercellularity may differ from other MCNS forms as regards age at
      presentation and renal function. We also suggest that IgM nephropathy with normal
      light microscopy is similar to MCNS.

PMID- 10946808
TI  - Haemostatic changes in systemic inflammatory response syndrome during continuous
      renal replacement therapy.
AB  - BACKGROUND: Endothelial damage and hemostatic imbalance play an important role in
      the evolution of the Systemic Inflammatory Response Syndrome (SIRS) into the
      Multiple Organ Dysfunction Syndrome (MODS). In Acute Renal Failure associated
      with SIRS, different types of Continuous Renal Replacement Therapies (CRRT) may
      give non-renal benefits by modifying the levels of some factors related to those
      disturbances. METHODS: Forty patients with SIRS-associated ARF were randomised to
      receive either continuous venovenous hemofiltration (CVVH) or continuous
      venovenous hemodiafiltration (CVVHDF) for the first 24 h. Afterwards the CRRT
      method was reversed. The group treated with CVVH moved to CVVHDF and that treated
      with CVVHDF to CVVH for the next 24 h. Plasma levels of: von Willebrand Factor
      (vWF), thrombomodulin, plasminogen activity inhibitor type 1 (PAI-1: antigen and
      activity), tissue type plasminogen activator (t-PA: antigen), prothrombin
      fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT) were measured
      previously to CRRT (base-line), and after 24 and 48 hours of therapy.
      Multivariate ANOVA was the statistical method used. RESULTS: In the MANOVA study
      a significant decrease in PAI-1 activity during the treatment procedure was
      observed (horizontality p <0.05). PAI-1 antigen showed a tendency to decrease
      although without statististical significance. There were no significantly
      different changes in the other factors analysed during either CRRT (parallelism p
      >0.05). At the base-line point, all the factors were higher than normal values in
      healthy adults. CONCLUSIONS: The present study suggests that CRRT, in patients
      with SIRS, may promote a decrease in PAI-1 and consequently, a better outcome.
      There were no differences between the CVVH and the CVVHDF methods regarding the
      factors analysed. The present data confirms that there is an important
      endothelial and hemostatic dysfunction in SIRS from the early phases.

PMID- 10946809
TI  - Membranous glomerulonephritis (MGN)

PMID- 10946810
TI  - Induction of cytotoxic T cells and their antitumor activity in mice transgenic
      for carcinoembryonic antigen.
AB  - In order to develop immunotherapy strategies that are based on eliciting immune
      responsiveness to the self-antigen, human carcinoembryonic antigen (CEA), we
      examined whether cytotoxic T lymphocyte (CTL) activity against CEA could be
      elicited in CEA-transgenic and nontransgenic mice. CEA-transgenic [C57BL/ 6
      TGN(CEAGe)18FJP] and nontransgenic mice were primed with CEA-transfected
      syngeneic fibroblasts in combination with Corynebacterium parvum. Spleen cells
      from immunized mice were cultured with irradiated syngeneic MC-38 colon carcinoma
      cells transfected with CEA (MC-38.CEA) as stimulators prior to the measurement of
      CTL activity. Primed nontransgenic spleen cells showed augmented CTL activity
      against MC-38.CEA cells as compared with control parental MC-38 cells,
      nontransfected or transfected with vector only. Moreover, primed CEA transgenic
      spleen cells showed augmented CTL activity against MC-38.CEA cells that was
      similar to that observed in nontransgenic mice. All CTL clones derived from
      either transgenic or nontransgenic mice showed cross-reactivity with MC-38 cells
      expressing the CEA-related antigen, nonspecific cross-reacting antigen, but not
      biliary glycoprotein. CEA-specific CTL clones were not identified. Adoptive
      transfer of cloned CTL resulted in inhibition of MC-38.CEA but not MC-38.BGP
      tumor growth. Tumor cures were elicited in mice treated with a combination of
      cloned CTL and cyclophosphamide. Histopathological examination of CEA-expressing
      colons from either immunized mice or recipients of cloned CTL did not reveal any
      autoimmune reactions. These studies demonstrate that CTL recognizing cross
      reactive class I epitopes on the CEA molecule can be induced in transgenic mice.
      The expression of these epitopes on tumor cells creates effective targets for CTL
      in vivo without inducing adverse reactions in CEA-expressing normal tissues.
      Since anti-CEA CTL have been generated in humans, CEA-transgenic mice may be a
      useful model to study vaccines that are based on CTL effector mechanisms.

PMID- 10946811
TI  - Development of a new vaccine formulation that enhances the immunogenicity of
      tumor-associated antigen CaMBr1.
AB  - Aberrant glycosylation is one of the most constant traits of malignant cells. The
      CaMBr1 hexasaccharide antigen, originally defined on the human breast carcinoma
      cell line MCF7, is expressed on some normal tissues but overexpressed in a high
      percentage of human breast, ovary, prostate and lung carcinomas. CaMBr1
      overexpression is associated with poor prognosis. The epitope consists of the
      tetrasaccharide Fuc(alpha1-2)Ga1(beta1-3)GalNAc(beta1-3)Ga1alpha-O-spacer, which
      has recently become available as a synthetic oligosaccharide. Here we report the
      CaMBr1 tetrasaccharide conjugation to two different carrier proteins (CRM197 and
      KLH) and the evaluation of conjugate immunogenicity in mice following their
      administration in various vaccine formulations with two adjuvants (MPL-SE and
      Detox-PC). Radioimmunoassay to determine the level and isotype of anti
      tetrasaccharide antibodies in mouse sera, and cytofluorimetric analysis and 51Cr
      release assay on human tumor cells, to evaluate specificity of binding and
      complement-dependent lysis respectively, identified CaMBr1-CRM197, in association
      with the MPL-SE adjuvant, as the best vaccine formulation. This combination
      induced (1) production of tetrasaccharide-specific antibodies, with negligible
      side-effects; (2) antibodies with complement-mediated cytotoxic activity on human
      CaMBr1-positive cells and (3) a high titer of IgG1 detected in sera obtained 3
      months after the first injection, indicating that the anti-tetrasaccharide
      antibody response was mediated by T cell activation. The availability of CaMBr1
      glycoconjugate in the minimal and functional antigenic structure and the
      identification of an efficacious vaccine formulation opens the way to exploring
      the activity of this glycoconjugate in a clinical setting.

PMID- 10946812
TI  - A low-level expression of human MUC1 mucin enhances lethality of murine tumor
      cells.
AB  - We report here the development of a mouse mammary adenocarcinoma cell line
      containing full-length human MUC1 cDNA that can be more lethal than the parental
      cell line. The metastatic murine mammary adenocarcinoma cell line 410.4 was
      transfected with cDNA coding for a 42-tandem-repeat version of human MUC1. Two
      cell lines were selected, one for stable, high expression in vitro of cell
      surface MUC1 (GZHi) and one for stable, low expression in vitro of cell-surface
      MUC1 (GZLo). Following subcutaneous challenge of CB6F1 mice with various doses of
      tumor cells, GZHi tumors showed loss of MUC1 expression; negligible amounts of
      serum MUC1 mucin were detected and the mice survived longer than mice challenged
      with GZLo or wild-type (410.4) tumor cells. Mice challenged with GZLo tumor cells
      had shorter survival times than mice challenged with either GZHi or 410.4 tumor
      cells. GZLo-challenged mice that showed rapidly increasing serum MUC1 mucin
      levels several weeks prior to death had a shorter survival than mice without
      detectable rising MUC1 serum levels. Surprisingly, SCID-BEIGE mice challenged
      with GZLo cells also survived for a shorter time than those challenged with
      either GZHi or 410.4 cells. This suggests that MUC1 mucin may also enhance the
      aggressiveness of GZLo tumors by non-immune mechanisms.

PMID- 10946813
TI  - Alpha(v)beta3 expression on blood vessels and melanoma cells in primary lesions:
      differential association with tumor progression and clinical prognosis.
AB  - The alpha(v)beta3 integrin has emerged as a key mediator in angiogenesis. Its
      role in tumor-induced angiogenesis is supported by its up-regulation in vivo in
      the vasculature of a number of different types of carcinoma. The potential
      clinical significance of alpha(v)beta3 expression on blood vessels in carcinomas
      is suggested by its association with tumor progression. Currently no information
      is available about the clinical significance of alpha(v)beta3 expression on the
      vasculature of lesions of melanocytic origin. Since we have previously found that
      alpha(v)beta3 expression on melanoma cells in primary lesions is associated with
      a poor prognosis, in the present study we have compared alpha(v)beta3 expression
      on blood vessels and on cells of melanocytic origin in nevi and in malignant
      melanoma lesions. In addition we have examined the lesions for expression of the
      alpha(v) subunit to gain information on the regulation of alpha(v)beta3
      expression on endothelial cells and on cells of the melanocyte lineage.
      alpha(v)beta3 expression on endothelial cells and on melanocytic cells was a
      relatively sensitive and specific marker for malignant lesions. However,
      alpha(v)beta3 expression on endothelial cells in primary melanoma lesions was not
      associated with the prognosis of the disease. The alpha(v) subunit and the
      alpha(v)beta3 complex were differentially expressed on endothelial cells and on
      melanocytic cells, implying that different regulatory pathways control their
      expression. This finding may account for the differential clinical significance
      of alpha(v)beta3 expression on tumor vasculature and on melanoma cells we
      observed in our patient cohort. Lastly, alpha(v)beta3 may be a useful target for
      immunotherapeutic approaches in melanoma because of its high expression on the
      vasculature of all metastatic lesions tested and its restricted distribution in
      normal tissues.

PMID- 10946814
TI  - Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non
      neoplastic glia and low-grade astrocytoma differ from malignant glioma.
AB  - Many of the actions and receptor components of interleukin-13 (IL-13), a
      pleiotrophic cytokine with immunotherapeutic potential, are shared with IL-4.
      Because human low-grade astrocytoma cells express IL-4 receptors and their growth
      is arrested by IL-4, we speculated that IL-13 sensitivity and receptor expression
      might also be present. The purpose of the current study was to investigate IL-13
      receptor components and sensitivity in a series of glial cell lines derived from
      adult human non-neoplastic cerebral cortex, low-grade astrocytoma, anaplastic
      astrocytoma, and glioblastoma multiforme. Unlike peripheral blood lymphocytes
      (PBL), glial cells did not express IL-2 receptor gamma chain. IL-13 receptor
      alpha-1 (IL-13Ralpha1), however, was present in 11/13 glial lines and PBL.
      Deficient cell lines were all glioblastoma-derived. All anaplastic astrocytoma
      and glioblastoma but not other glial lines or PBL expressed IL-13 receptor alpha
      2 (IL-13Ralpha2). In non-neoplastic glia, low-grade, and anaplastic astrocytoma,
      IL-13 decreased DNA synthesis, an effect reversible with antibody to IL-4Ralpha.
      Results indicate that low-grade astrocytoma cells resemble non-neoplastic glia in
      terms of IL-13 sensitivity and IL-4Ralpha/IL-13Ralpha1 receptor profile but
      alterations occur with malignant progression. Glioblastoma cells were uniformly
      insensitive to IL-13 and, unlike other glia, failed to phosphorylate STAT6 after
      IL-13 challenge. Data suggest that IL-13 and analysis of IL-13 receptors may have
      clinical application in glial tumors.

PMID- 10946815
TI  - Modulation of interleukin-12 synthesis by DNA lacking the CpG motif and present
      in a mycobacterial cell wall complex.
AB  - A mycobacterial cell wall complex prepared from the non-pathogenic microorganism
      Mycobacterium phlei, where mycobacterial DNA is preserved and complexed to cell
      wall fragments, possesses anticancer and immunomodulatory activity. DNA from a
      number of prokaryotes has been found to modulate the immune system and to induce
      cytokine synthesis. We have therefore determined whether the DNA associated with
      this complex has the ability to induce the synthesis of interleukin-12 (IL-12), a
      potent anticancer cytokine. Mycobacterial DNA complexed with cell wall fragments
      or DNA purified from M. phlei induced IL-12 synthesis by murine and human
      monocytes and macrophages in vitro, and was capable of inducing IL-12 synthesis
      in vivo in mice following i.p. administration. Neutralization of DNA with
      cationic liposomes or digestion with DNase I significantly decreased the ability
      of the cell wall complex to induce IL-12. CpG methylation of DNA extracted from
      these cell walls or from M. phlei did not affect the induction of IL-12 synthesis
      by monocytes and macrophages. In contrast, CpG methylation of DNA from
      Escherichia coli abolished its ability to induce IL-12 synthesis. These results
      demonstrate that unmethylated CpG motifs present in M. phlei DNA are not a
      prerequisite for the induction of IL-12 synthesis. The size of the mycobacterial
      DNA, in the range of 5 bp to genomic DNA, did not influence its capacity to
      induce IL-12. Our results emphasize that M. phlei DNA associated with the cell
      wall complex makes a significant contribution to the overall immunomodulatory and
      anticancer activity of this mycobacterial cell wall preparation and that these
      activities are not correlated with the presence of CpG motifs.

PMID- 10946816
TI  - Resistance of ex vivo expanded CD3+CD56+ T cells to Fas-mediated apoptosis.
AB  - A variety of malignancies express Fas ligand (FasL), which can induce apoptosis
      in effector lymphocytes and may limit the success of cellular immunotherapy. Our
      laboratory has been investigating a population of ex vivo activated T cells,
      termed cytokine-induced killer (CIK) cells. These cells share functional and
      phenotypic properties with natural killer cells and a subset of cytolytic cells
      have the phenotype CD3+CD56+. CIK cells expand in culture, have significant
      antitumor activity and are presently being tested in phase I/II clinical trials.
      In this study, we investigated the sensitivity of CIK cells to Fas-mediated
      apoptosis. Fas engagement leads to apoptosis in small numbers of CIK cells and
      does not significantly influence antitumor cytotoxicity. CIK cells will undergo
      apoptosis following Fas engagement when protein synthesis is inhibited,
      suggesting the expression of antiapoptotic genes. Evaluation of antiapoptotic
      gene transcripts shows an upregulation in the expression of cFLIP, Bcl-2, Bcl-xL,
      DAD1 and survivin. Resistance to Fas-mediated apoptosis may come about through an
      in vitro selection for Fas resistance, since CIK cells synthesize FasL and
      supernatant from CIK cultures contains biologically active soluble FasL, which
      can be inhibited with Fas:Fc. These results indicate that CIK cells are a
      suitable form of immunotherapy against FasL-positive tumors.

PMID- 10946818
TI  - Baking soda toxicity.

PMID- 10946817
TI  - Treating functional gastrointestinal disorders with antidepressants.

PMID- 10946819
TI  - Acromegaly in a hemophilic patient infected with the hepatitis C and human
      immunodeficiency viruses.

PMID- 10946820
TI  - Lipid abnormalities in babesiosis.

PMID- 10946821
TI  - Seasonal variation in the occurrence of epistaxis.

PMID- 10946823
TI  - Expression of heat shock proteins 65, 72 and 90 in mercuric chloride-treated
      human peripheral blood mononuclear cells.
AB  - Peripheral blood mononuclear cells (PBMC) were challenged with different
      concentrations of mercuric chloride and the expression of heat shock protein
      (hsp) 65, 72 and 90, were investigated by an indirect peroxidase method as well
      as the proliferation was measured by uptake of tritiated thymidine into DNA. Hsp
      65 immunoreactivity was peripherally located in the cells at a mercuric chloride
      concentration of 5.5-2.8x10(-5) mol/L, which also gave a decreased DNA synthesis.
      Hsp 72 positive cells, with a nuclear and cytoplasmic immunoreactivity, were
      found at a concentration of 5.5-2.2x10(-5) mol/L. Hsp 90 positive cells also with
      an immunoreactivity at a nuclear and cytoplasmic level, were found at 1.1x10(-5)
      5.5x10(-6) mol/L. A stimulated DNA synthesis was obtained already at 2.2x10(-5)
      mol/L and was found down to 5.5x10(-6) mol/L. High concentrations of mercuric
      chloride might induce expression of hsp 65 and 72 as a protective mechanism. Hsp
      90 as well as hsp 72 might be involved in the proliferation of human PBMC to
      mercuric chloride. Thus, this expression of hsp 72 may have a dual role.

PMID- 10946822
TI  - Enhanced interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha
      production by LPS stimulated human monocytes isolated from HIV+ patients.
AB  - Periodontal disease and tooth loss is a common finding among advanced HIV+
      patients. In addition to local oral lipopolysaccharide (LPS) stimulation,
      systemic up-regulation of monocyte pro-inflammatory cytokine secretion may also
      be involved in the pathogenesis of HIV disease. A study was undertaken to
      investigate IL-1beta, IL-6 and TNF-alpha production by resting and LPS stimulated
      monocytes isolated from HIV+ patients and also to investigate the relationship of
      the patient's HIV viral load status to the cytokine production. Whole blood
      samples in EDTA were collected from 39 HIV-1 infected patients and 20 age and sex
      matched uninfected controls. Plasma was separated by centrifugation. Viral load
      was determined using a quantitative RT-PCR. Monocytes were isolated by Ficoll
      hypaque gradient separation followed by overnight plastic adherence. Cultured
      monocytes (1x10(6)/ml) were stimulated with LPS (1 microg/ml) of either P.
      gingivalis or F. nucleatum for 2, 8, 24 and 48 h and supernatant fluids were
      collected. IL-1beta, IL-6, and TNF-alpha levels in supernatant fluids were
      estimated by ELISA. Increased overall production of IL-1beta, IL-6 and TNF-alpha
      by LPS stimulated monocytes isolated from HIV-1 infected patients was observed
      when compared to HIV-1 uninfected controls. LPS stimulated monocytes from HIV-1
      infected patients with high viral load (HVL) produced significant (p<0.05)
      elevations in these pro-inflammatory cytokines when compared to HIV-1 uninfected
      controls. Both LPS of P. gingivalis and F. nucleatum produced a comparable
      cytokine production by monocytes after 8 h of stimulation. These data suggest
      that enhanced IL-1beta, IL-6 and TNF-alpha is produced by monocytes/macrophages
      isolated from HVL HIV+ patients and may be involved in the overall pathogenesis
      of HIV-1 infection.

PMID- 10946824
TI  - Dietary conjugated linoleic acid protects against end stage disease of systemic
      lupus erythematosus in the NZB/W F1 mouse.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring fatty acid with anti
      carcinogenic, anti-atherosclerotic and immune-enhancing activities. Dietary CLA
      accelerated the onset of proteinuria in autoimmune-prone NZB/W F1 mice but did
      not affect anti-DNA antibody production. Body weight of the CLA group was
      decreased compared to the control group at the time proteinuria first developed.
      CLA group also had slightly earlier mortality than control fed mice, however the
      mean days of survival did not differ between CLA and control fed mice. Body
      weight loss between proteinuria onset and death was approximately twice as much
      in the control group as in the CLA group. Moreover, duration between proteinuria
      and death was longer in the CLA than in the control group. Our data suggested
      that dietary CLA may accelerate the autoimmune symptoms of NZB/W F1 mice,
      however, CLA protected against the disease related body weight loss and prolonged
      survival after proteinuria.

PMID- 10946825
TI  - Evaluation of the natural immunity in pups inoculated with a modified-live canine
      parvovirus type 2b (CPV-2b) strain.
AB  - Three pups 2-4 months old were vaccinated subcutaneously with the modified live
      canine parvovirus, CPV-2b/29-97 strain. During an observation period of two weeks
      pups remained clinically health, exhibiting a vigorous post-vaccinal active
      serological response (haemoagglutinating inhibiting antibody titers for CPV-2
      ranging from 1:2560 to 1:5120 at 21 days post inoculation). Phagocytosis and
      killing of Candida albicans exerted by polymorphonuclear cells and monocytes did
      not undergo significant modifications 3-6 days post vaccination up to 30 days.
      Antibacterial activity mediated by peripheral blood lymphocytes (Salmonella typhi
      was used as a target) was slightly, but not significantly decreased 3 days post
      vaccination. Conclusively, in pups the CPV type 2b vaccine seems to be safe as
      far as natural immune responses are concerned, while its immunogenicity is
      preserved.

PMID- 10946826
TI  - rIL-2-stimulated splenocytes reactivate the NO2-producing ability of macrophages
      infected by Leishmania donovani.
AB  - Infection with L. donovani down-regulates immunity and parasite clearance by
      macrophages. Treatment with IL-2-stimulated-splenocytes activate parasiticidal
      action in vitro in peritoneal macrophages of C57BL/6 (Lsh(s)) mice and also was
      effective in stimulating infected macrophages to produce NO2-.

PMID- 10946827
TI  - Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats
      by Perilla frutescens.
AB  - We investigated the effect of aqueous extract of Perilla frutescens (Labiatae)
      (PFAE) on the mast cell-mediated immediate-type allergic reactions. PFAE (0.05 to
      1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound
      48/80 in rats. PFAE (0.1 and 1 g/kg) also significantly inhibited local allergic
      reaction activated by anti-DNP IgE. When PFAE was pretreated at the same
      concentrations with systemic allergic reaction test, the plasma histamine levels
      were reduced in a dose-dependent manner. PFAE (10(-3) to 1 mg/ml) dose
      dependently inhibited the histamine release from rat peritoneal mast cells (RPMC)
      activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC,
      When PFAE (1 mg/ml) was added, transiently and significantly increased about 4
      fold compared with that of basal cells. Moreover, PFAE (0.001 and 0.01 mg/ml) had
      a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor
      alpha production. These results indicate that PFAE inhibits mast cell-mediated
      immediate-type allergic reactions in vivo and in vitro.

PMID- 10946828
TI  - Cytokine profile and natural killer cell activity in Listeria monocytogenes
      infected mice treated orally with Petiveria alliacea extract.
AB  - In this work, we investigated the effects of Petiveria alliacea extract on the
      production of Th1-type and Th2-type cytokines and on NK cells activity in normal
      and Listeria monocytogenes infected mice. Our results demonstrated that in
      normal/non-infected mice P. alliacea administration led to increased levels of
      Interleukin-2 (IL-2). The infection alone enhanced INF-gamma levels and NK cell
      activity at 48 and 72 hours of infection. The treatment with five consecutive
      doses of 1000 mg/kg/day of P. alliacea extract, given previously to infection,
      led to further increases in IL-2 levels, in relation to normal/non-infected/P.
      alliacea treated controls, and in INF-gamma levels at 72 h of infection, compared
      to infected mice. On the other hand, the production of IL-4 and IL-10 were not
      altered either by the infection or by the treatment with P. alliacea extract. NK
      cells activity increased at 48 h and 72 h following the inoculation of the
      bacteria. When mice were treated with P. alliacea previously to infection, NK
      activity was higher than that observed at 48 h, 72 h and 120 h of infection in
      the infected animal. Based on these findings we suggest that P. alliacea up
      regulates anti-bacterial immune response by enhancing both Th1 function and the
      activity of NK cells.

PMID- 10946829
TI  - Taraxacum officinale inhibits tumor necrosis factor-alpha production from rat
      astrocytes.
AB  - Substance P (SP) can stimulate production of tumor necrosis factor-alpha (TNF
      alpha) from astrocytes stimulated with lipopolysaccharide (LPS). The objective of
      the current study was to determine the effect of Taraxacum officinale (TO) on the
      production of TNF-alpha from primary cultures of rat astrocytes. TO (100 and 1000
      microg/ml) significantly inhibited the TNF-alpha production by astrocytes
      stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate TNF
      alpha production from LPS-stimulated astrocytes while having no effect on
      astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated
      inhibition of TNF-alpha production from primary astrocytes by TO. Treatment of TO
      (100 and 1000 microg/ml) to astrocytes stimulated with both LPS and SP decreased
      IL-1 production significantly. Moreover, the production of TNF-alpha by LPS and
      SP in astrocytes was progressively inhibited with increasing amount of IL-1
      neutralizing antibody. Our results suggest that TO may inhibit TNF-alpha
      production by inhibiting IL-1 production and that TO has an antiinflammatory
      activity in the central nervous system.

PMID- 10946830
TI  - Inhibitory effect of interleukin-1alpha-induced apoptosis by Polygala tenuifolia
      in Hep G2 cells.
AB  - A human hepatoma cell line, Hep G2 cells are reliable for the study of alcohol
      induced hepatotoxicity. In this study, we investigated the effect of an aqueous
      extract of Polygala tenuifolia WILLDENOW (Polygalaceae) roots (PTAE) on ethanol
      (EtOH)-induced cytotoxicity in Hep G2 cells. PTAE (0.01-1 microg/ml) dose
      dependently inhibited the EtOH-induced interleukin-1alpha (IL-1alpha) secretion.
      PTAE (0.01-1 microg/ml) also inhibited the EtOH- and IL-1alpha-induced
      cytotoxicity. Furthermore, we found that PTAE inhibited the IL-1alpha-induced
      apoptosis of Hep G2 cells. These results suggest that PTAE may prevent the EtOH
      induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

PMID- 10946831
TI  - Inhibitory effects of methanol extract of seeds of Job's Tears (Coix lachryma
      jobi L. var. ma-yuen) on nitric oxide and superoxide production in RAW 264.7
      macrophages.
AB  - Overproduction of nitric oxide (NO) or superoxide (O2-) by activated macrophages
      is known to be involved in acute or chronic inflammation. The seeds of Job's
      Tears (Coix lachryma-jobi L. var. ma-yuen) have been used as anti-inflammatory
      medicine and health food. However, it is still unclear how the seeds show anti
      inflammatory properties. Using murine macrophage-like RAW 264.7 cells, we tried
      to know whether the overproduction of NO and O2 by activated macrophages could be
      prevented by the methanol (MeOH) extract of the seeds of Job's Tears. RAW 264.7
      cells were activated with interferon-gamma plus lipopolysaccharide to produce NO
      and with pholbol ester to produce O2-. The MeOH extract showed marked inhibition
      of NO production by activated RAW 264.7 cells in a dose-dependent manner via
      suppression of inducible NO synthase mRNA expression. The MeOH extract also
      showed inhibition of O2- production by activated RAW 264.7 cells in dose- and
      time-dependent manners, possibly by interfering with NADPH oxidase machinery of
      macrophages. Collectively, these results demonstrate that the MeOH extract of the
      seeds of Job's Tears shows anti-inflammatory properties which may, in part,
      involve an inhibition of NO and O2- production by activated macrophages.

PMID- 10946832
TI  - Effects of treatment with amphetamine and diazepam on Mycobacterium bovis-induced
      infection in hamsters.
AB  - Tuberculosis is an example of an infection with an intracellular bacterium in
      which sensitivity is determined mainly by the host response. Macrophages are the
      architectural and functional units of the granulomas described in tuberculosis.
      Treatment with amphetamine (AMPH) and diazepam has been reported to decrease
      macrophage activity. The present experiment was undertaken to investigate the
      effects of AMPH and/or diazepam given alone or in combination on hamster
      resistance to Mycobacterium bovis. The effects of these treatments on serum
      cortisol levels were also studied. Adult hamsters were treated i.p. with AMPH
      (group E1 = 1.0 or 2.0 mg/kg/day), with AMPH (group E2 = 1.0 or 2.0 mg/kg/day)
      plus diazepam (2.0 mg/kg/day), with diazepam (group E3 = 2.0 mg/kg/day), or with
      control vehicles (1.0 ml/kg/day) for 40 days. Six days after the beginning of the
      treatments, the animals received identical inoculum concentrations of M. bovis.
      Hamsters treated with AMPH plus diazepam exhibited: 1) increased weight loss; 2)
      increased mortality; 3) increased scores of M. bovis colony forming units (CFU)
      isolated from liver, lung and spleen; 4) increased granuloma areas measured in
      the liver, lung and spleen. These effects were not induced by AMPH (1.0 or 2.0
      mg/kg/day) given alone and were produced by diazepam (2.0 mg/kg/day) treatment
      per se. Furthermore, AMPH (2.0 mg/kg/day) and diazepam (2.0 mg/kg/day) given
      alone or in combination for 20 days increased the serum levels of cortisol in
      relation to control hamsters, with the effect being higher in the animals treated
      with both drugs. The present data, which demonstrate an impaired defense against
      M. bovis in hamsters treated with AMPH plus diazepam or with diazepam alone, were
      tentatively explained on the basis of a direct and/or indirect action of the
      drugs on macrophage/lymphocyte activity. In the former case, the effects may be
      related to stimulation of peripheral benzodiazepine receptor sites (PBR) present
      on macrophages/lymphocytes and/or to a direct effect of ACTH on immune cells,
      while in the latter they may be mediated by cortisol via PBR and ACTH stimulation
      of the adrenals.

PMID- 10946833
TI  - Degradation of ochratoxin A by Aspergillus species.
AB  - Mycotoxin contamination of agricultural products is a serious health hazard
      throughout the world. Besides attempts to eliminate mycotoxins from contaminated
      substrates by physical and chemical methods, the ability of microbes to degrade
      mycotoxins is now being widely examined. In this study, several Aspergillus
      species were examined for their ability to degrade ochratoxin A. A. fumigatus and
      black Aspergillus strains were found to detoxify ochratoxin A in culture media.
      The kinetics of ochratoxin A detoxification by an atoxigenic A. niger strain was
      examined by thin layer chromatography, high-performance liquid chromatography and
      an immunochemical technique. A. niger CBS 120.49 was found to effectively
      eliminate ochratoxin A from both liquid and solid media, and the degradation
      product, ochratoxin alpha, was also decomposed.

PMID- 10946834
TI  - Biochemical characterization of lactic acid bacteria isolated from spontaneous
      fermentation of 'Almagro' eggplants.
AB  - A total of 149 strains of lactic acid bacteria isolated from the spontaneous
      fermentation of 'Almagro' eggplants were characterized and identified. Of the
      isolates, 148 were determined as belonging to the genus Lactobacillus. A coccoid,
      gram-positive database-negative isolate was obtained in the early stages of
      fermentation. The Lactobacillus strains were divided into six groups based on
      sugar fermentation patterns and other physiological and morphological
      characteristics, and were identified as Lactobacillus plantarum biotype 1
      (54.4%), Lactobacillus brevis biotype 2 (19.5%), Lactobacillus fermentum (9.4%),
      Lactobacillus brevis biotype 3 (5.4%), Lactobacillus pentosus (4.7%) and nine
      strains, which were not included in the previous species, were grouped as
      Lactobacillus spp. (6.0%). Fermentation was initiated by Lactobacillus brevis
      biotype 2 and Lactobacillus fermentum. During the fermentation Lactobacillus
      plantarum became the predominant species.

PMID- 10946835
TI  - Characterization of natural isolates of Lactobacillus strains to be used as
      starter cultures in dairy fermentation.
AB  - The technological relevant characteristics of five homofermentative lactobacilli
      strains, isolated from natural fermented hard cheeses, were studied. Isolates CRL
      581 and CRL 654, from Argentinian artesanal hard cheeses, and isolates CRL 1177,
      CRL 1178, and CRL 1179, from Italian Grana cheeses, were identified as
      Lactobacillus delbrueckii subsp. lactis and Lactobacillus helveticus,
      respectively, by physiological and biochemical tests, SDS-PAGE of whole-cell
      proteins and sequencing of the variable (V1) region of the 16S ribosomal DNA. All
      strains showed high levels of beta-galactosidase activity. However, proteolytic
      activity varied widely among isolates. Strains CRL 581, CRL 654, and CRL 1177
      hydrolyzed alpha- and beta-caseins and were able to coagulate reconstituted skim
      milk in less than 16 h at 42 degrees C. According to the substrate specificity,
      these proteinases have a caseinolytic activity comparable to that of the P(III)
      type of lactococcal proteinases. No strains produced inhibitor substances
      (bacteriocin) and all were insensitive to attack by 14 L. helveticus- and L.
      delbrueckii subsp. lactis-specific bacteriophages.

PMID- 10946836
TI  - Typing of non-Saccharomyces yeasts with enzymatic activities of interest in wine
      making.
AB  - Enzymatic activity of potential interest in wine-making was studied for 182 non
      Saccharomyces yeasts isolated from musts before and at the onset of fermentation
      at wine cellars operating under the La Mancha Appellation of Origin in Spain.
      Tests were carried out on plates containing differential substrates appropriate
      for each case (casein, gelatin, polygalacturonic acid, and arbutin) to determine
      whether each of the isolates exhibited proteolytic, polygalacturonase, and beta
      glucosidase activities. Nearly 80% of the wild yeasts possessed one or more
      enzymes of biotechnological interest. Once the enzymatic activities of the
      isolates had been established, 69 of the isolates that exhibited pronounced
      enzymatic activity and 11 randomly selected isolates that were devoid of any
      activity were typed using PCR/RFLP, which gave 13 different molecular profiles.
      The isolates for each of the profiles were then identified by classical methods.
      The enzyme beta-glucosidase was linked to the species Metschnikowia pulcherrima,
      and polygalacturonase activity was common in most of the species identified.
      Proteolytic activity was observed in Pichia membranifaciens and in Metschnikowia
      pulcherrima. Typing revealed the possibility of intraspecific differences in
      Pichia membranifaciens, because six different molecular profiles with one or more
      shared restriction bands were recorded for that species.

PMID- 10946837
TI  - Effects of Lactobacillus strains on the ripening and organoleptic characteristics
      of Arzua-Ulloa cheese.
AB  - Seven batches of Arzua-Ulloa, a short-ripened soft cow's milk cheese produced in
      Galicia (NW Spain), were prepared from pasteurized milk. Two control batches of
      cheese (CB) were made with an acid-aromatic starter containing Lactococcus lactis
      subsp. lactis and Lactococcus lactis subsp. lactis var. diacetylactis, isolated
      from raw-milk Arzua-Ulloa cheeses. Five batches of cheese (LB) were made with the
      acid-aromatic starter plus one of five strains of mesophilic homofermentative
      Lactobacillus spp.: four of them isolated from raw-milk Arzua-Ulloa cheese
      (characterized in previous works) and the remaining was a commercial
      Lactobacillus strain. Higher counts of mesophilic viable bacteria, lactic acid
      bacteria and citrate-fermenting bacteria were found on days 1 or 15 of ripening,
      while higher counts of lactobacilli were found on day 30 of ripening. On day 1 of
      ripening the highest diacetyl-acetoin content was noted in the CB, but after day
      15 the diacetyl-acetoin content was similar or higher in three of the five LB.
      The mean degradation of beta-casein in CB was higher than in LB, while the
      degradation of alpha(s1)-casein was higher in LB. The mean contents of nitrogen
      soluble fractions were slightly higher in the LB than in the CB. Volatile free
      fatty acid (VFFA) contents were, in general, greater in LB than in CB and maximum
      amounts were determined on day 15 of maturation. Sensorial analysis indicated a
      more acid taste was in LB, while bitter and astringent tastes were more intense
      in CB. A positive correlation was found between beta-casein degradation and
      bitter taste. Yogurt and butter aromas were more intense in CB and in two of the
      five LB. Firmness was lower in LB and a negative correlation was found between
      this parameter and alpha(s1)-casein degradation. Crumbliness showed a positive
      correlation with beta-casein degradation. The use of the Lactobacillus strains
      assessed in this study is recommended for Arzua-Ulloa cheese manufacture, in
      order to enhance the desirable characteristics of this cheese variety, i.e., a
      soft texture due to alpha(s1)-casein proteolysis but without the bitter taste due
      to beta-casein degradation and a spicy and slightly rancid aroma and taste.

PMID- 10946838
TI  - Evaluation of the impact of short-term temperature abuse on the microbiology and
      shelf life of a model ready-to-use vegetable combination product.
AB  - The growth dynamics of indigenous aerobic mesophilic populations (AMP), lactic
      acid bacteria (LAB) and inoculated (Listeria spp.) microbial populations on
      cooked and fresh vegetable products, packaged as separate entities and in
      combination, subjected to temperature fluctuation, were assessed. Microbial
      proliferation was temperature and product dependent, being most pronounced at 12
      degrees C in all products with maximum growth rates of 0.140, 0.175 and 0.126
      log10 CFU/g per h being identified for Listeria, aerobic mesophilic and LAB
      populations, respectively. Listeria spp. and AMP generally demonstrated higher
      rates of growth within products containing cooked vegetables. Prolonged storage
      at 3 degrees C resulted in a reduced ability by AMP and Listeria spp. to
      proliferate upon exposure to growth temperatures; this was not the case with LAB
      populations. Comparison of Listeria population estimates made using selective
      (Oxford) and non-selective (nutrient agar) identified reduced recovery on the
      former. The magnitude of the deviation increased with the duration of exposure of
      Listeria populations to 3 degrees C with recoveries on selective systems being
      reduced by 6.3% immediately after inoculation and 82.3% after 168 h at 3 degrees
      C, respectively. Growth of populations associated with exposure to abuse
      temperatures was not accompanied by significant changes in product colour (P <
      0.05).

PMID- 10946839
TI  - The effect of fungal competition on colonization of maize grain by Fusarium
      moniliforme, F. proliferatum and F. graminearum and on fumonisin B1 and
      zearalenone formation.
AB  - The effect of water activity (0.98, 0.95, 0.93) and temperature (15, 25 degrees
      C) on fungal growth and toxin production from interactions between isolates of
      Fusarium moniliforme and F. proliferatum producing fumonisin, and an isolate of
      F. graminearum producing zearalenone, incubated at the same time on irradiated
      maize grains were determined in vitro. Populations (CFUs) of F. moniliforme and
      F. proliferatum were reduced to a greater or lesser extent by the presence of F.
      graminearum under all conditions tested, while that the presence of F.
      moniliforme or F. proliferatum had a minor inhibitory effect on fungal
      populations of F. graminearum. Fumonisin B, production by F. proliferatum was
      inhibited under all conditions tested, while fumonisin B1 production by F.
      moniliforme was inhibited at 15 degrees C and enhanced at 25 degrees C in the
      presence of F. graminearum. The level of zearalenone was not significantly
      modified in the presence of F. moniliforme and F. proliferatum under the
      conditions tested.

PMID- 10946840
TI  - Recovery of Burkholderia pseudomallei and B. cepacia from drinking water.
AB  - Samples of drinking water were examined in order to evaluate the occurrence of
      two gram-negative bacteria: Burkholderia pseudomallei and B. cepacia. A total of
      85 samples were collected from public and private buildings in the province of
      Bologna (Italy). Other bacteriological indicators (heterotrophic plate count at
      22 and 36 degrees C) were also examined, together with physical and chemical
      parameters (temperature, pH, residual chlorine, total hardness and chemical
      oxygen demand (COD)). High levels of B. pseudomallei were recovered (mean value =
      578 cfu/100 ml) in about 7% of samples, while B. cepacia was recovered in 3.5%
      (mean value = < 1) of the samples. The two microorganisms were found to correlate
      positively with heterotrophic plate counts at 22 and 36 degrees C, but not with
      the physical and chemical parameters taken into consideration.

PMID- 10946841
TI  - Prevalence and contamination levels of Listeria monocytogenes in retail foods in
      Japan.
AB  - Retail foods in Japan were surveyed for the presence and contamination levels of
      L. monocytogenes. It was isolated from 12.2, 20.6, 37.0 and 25.0% of 41 minced
      beef, 34 minced pork, 46 minced chicken and 16 minced pork-beef mixture samples,
      respectively. MPN values were higher than 100/g in five (10.9%) minced chicken
      samples, but lower than 100/g in all minced beef, pork and pork-beef mixture
      samples. The organism was also isolated from 5.4% of the 92 smoked salmon samples
      at MPN values lower than 10/g, and from 3.3% of 213 ready-to-eat raw seafood
      samples at MPN values from lower than 0.3 to higher than 100/g. None of the 285
      vegetable samples were contaminated with L. monocytogenes. These findings
      indicate that ready-to-eat raw seafoods are relatively high risk among the foods
      surveyed in this study.

PMID- 10946842
TI  - Viruses and bivalve shellfish.
AB  - The epidemiological data clearly demonstrates that filter feeding bivalve
      shellfish can, and do, act as efficient vehicles for the transmission of enteric
      viruses transmitted by the faecal-oral route. This identified hazard has been
      documented as a cause for concern by various international agencies and has a
      long history. Disease outbreaks can occur on an epidemic scale as graphically
      illustrated by an outbreak of Hepatitis A in Shanghai, China in 1988 involving
      about 300,000 cases. Improvement of harvesting area water quality offers the most
      sustainable route to improvement in the virological quality of bivalve shellfish
      sold live. However there is growing awareness, and concern, that current
      regulatory standards based on faecal coliform monitoring do not fully protect the
      shellfish consumer from viral infection. New viral test methods based on PCR, and
      the development of alternative more reliable faecal pollution indicators, offer
      new approaches for the further development of public health controls. However,
      further work is required to build a scientific consensus and to understand the
      implications of their introduction into legislation.

PMID- 10946843
TI  - Diagnosis of foodborne viral infections in patients.
AB  - A significant global problem is the microbiological contamination of foods and
      water. The microorganisms associated with about half of the foodborne disease
      outbreaks still go unrecognized, primarily as a result of inadequate diagnostic
      methods and sampling. A significant amount of food- and waterborne diseases are
      associated with viruses, information that has been obtained only in recent years.
      Improved diagnostic methods have established that caliciviruses are the most
      important non-bacterial pathogens associated with food- and waterborne outbreaks,
      and are the major cause of seafood-associated gastroenteritis.

PMID- 10946844
TI  - Foodborne viral illness--status in Australia.
AB  - Norwalk-like virus contamination of oysters and orange juice, and hepatitis A
      virus contamination of oysters have been responsible for large outbreaks of
      foodborne viral disease in Australia. Rotavirus, adenovirus, astrovirus,
      parvovirus and other enteroviruses also contribute to the incidence of
      gastroenteritis in this country but the role of foods and waters in transmitting
      these viruses is unclear. Protocols for the investigation, surveillance and
      reporting of foodborne viral illness require further development to enable a more
      accurate description of the problem. Few laboratories have the capability to
      analyse foods for viruses and specific training in this technology is needed.
      Management of food safety in Australia largely relies on the implementation of
      HACCP principles, but these need to be adapted to address the specific risks from
      viruses.

PMID- 10946845
TI  - Receptors for NPY in peripheral tissues bioassays.
AB  - Neuropeptide Y (NPY) and its congeners, peptide YY (PYY) and the pancreatic
      polypeptide (PP), have a large spectrum of peripheral actions. NPY is found in
      peripheral neurons, co-localized or not with noradrenaline; PYY and PP are
      expressed in endocrine cells of the pancreas and in the intestine of vertebrates.
      NPY is the most abundant peptide in the brain and is involved in the regulation
      of food intake and of circadian rhythm. It intervenes also in the process of
      anxiety and memory. NPY is a potent vasoconstrictor, a cardiac stimulant, and may
      affect the gut through enteric neurons. PYY and PP act mainly on the
      gastrointestinal system; however, when in blood, they can cross-react with
      functional sites elsewhere and replace NPY in some parts of the brain (e.g.
      regions involved in feeding behavior). These peptides act through G protein
      coupled receptors (GPCR) of which five different types are known and have been
      cloned (1,2); functional sites (receptors) for NPY have been found in vessels,
      the gut, and in vasa deferentia (3-6).

PMID- 10946847
TI  - Effects of guanfacine on three forms of distraction in the aging macaque.
AB  - alpha-2 adrenoceptor agonists, such as clonidine and guanfacine, enhance
      attention in aged animals. According to one theory, alpha-2 receptor agonists
      improve attention by decreasing distractibility to task-irrelevant stimuli. In
      two healthy aging bonnet macaques, we investigated the effects of low-(0.001
      mg/kg) and high-dose (0.05 mg/kg) acute intramuscular guanfacine versus saline
      control on accuracy (number of trials correct) in three tasks requiring
      attention: delayed matching-to-sample, one-target visual tracking (test of
      focused attention) and two-target visual tracking (test of divided attention).
      Each task employed distracting stimuli in a different paradigmatic context. One
      monkey responded to guanfacine at both doses with significant rises in accuracy
      on all three tasks. The second monkey showed significant accuracy improvement for
      high-dose guanfacine only. No sedation was observed. These results suggest that
      guanfacine improves attention and reduces distractibility in multiple task
      contexts in healthy aging primates.

PMID- 10946846
TI  - Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction
      of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and
      p22phox by regulation of peroxisome proliferator-activated receptor alpha
      (PPARalpha) in primary endothelial cells.
AB  - We examined the effects of four 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors (pravastatin, simvastatin, fluvastatin, and cerivastatin) on
      the production and expression of inflammatory cytokines and on enzyme expression
      involving prostaglandin and superoxide production in cultured human umbilical
      vein endothelial cells (HUVEC). All HMG-CoA reductase inhibitors significantly
      reduced interleukin-1beta and -6 mRNA expression and their protein levels in the
      culture medium, and also inhibited cyclooxygenase-2 mRNA expression and their
      protein levels. And these drugs induced peroxisome proliferator-activated
      receptor alpha (PPARalpha) and PPARgamma mRNA expression and their protein levels
      in HUVEC and hepatocyte. Moreover, the mRNA levels of p22phox, a 22-kD subunit
      and the protein levels of p47phox, a 47-kD subunit of nicotine adenine
      dinucleotide phosphate (NADPH) oxidase, was decreased by treatment with either
      simvastatin, fluvastatin or cerivastatin, and this effect was reversed by
      mevalonate, geranylgeraniol, farnesol, and cholesterol. The changes induced by
      HMG-CoA reductase inhibitors might be due to regulation of cellular cholesterol
      content level, cellular cholesterol metabolic pathway, and cellular PPARalpha
      activity, which was related with inflammation. This unique anti-inflammatory
      effect in addition to its hypolipidemic action, may be beneficial in preventing
      the vascular complications that are induced by hyperlipidemia.

PMID- 10946848
TI  - Purification of a novel apolipoprotein H-like milk protein with ribonucleolytic
      and cell-free translation inhibitory activities.
AB  - A new whey protein designated apolipoprotein H-like whey protein, with a
      molecular weight of 62 kDa and an N-terminal amino acid sequence similar to that
      of apolipoprotein H, was isolated from bovine milk. The isolation procedure
      involved removal of globulin from acid whey by precipitation with 1.8M (NH4)2SO4,
      followed by addition of (NH4)2SO4 to attain a concentration of 3.6M. Subsequent
      steps included chromatography on CM-Sepharose and Mono S and elution of the
      adsorbed protein of interest with a linear NaCl gradient. The new whey protein
      displayed some ribonuclease (RNase) activity. It was most active at pH 7.5 with
      yeast transfer RNA (tRNA) as substrate and showed potent specific ribonucleolytic
      activity toward poly C. It inhibited cell-free translation in a rabbit
      reticulocyte lysate system with an IC50 of approximately 63 nM.

PMID- 10946849
TI  - Nifedipine induces apoptosis in cultured vascular smooth muscle cells from
      spontaneously hypertensive rats.
AB  - Apoptosis (programmed cell death) of smooth muscle cells (SMC) in blood vessels
      is an essential process involved in the control of vessel wall structure. Several
      antihypertensive drugs currently used in therapy may exert their pharmacological
      effects by promoting SMC apoptosis. The biochemical events which regulate SMC
      apoptosis in the vessel wall are complex, and not well understood. We therefore
      investigated whether treatment of cultured SMC from normotensive Wistar-Kyoto
      rats (WKY) and from spontaneously hypertensive rats (SHR) with selected
      antihypertensive drugs would induce SMC apoptosis. We treated aortic SMC from WKY
      and SHR in vitro with the L-type Ca2+ channel antagonist, nifedipine; with the
      nitric oxide donor, sodium nitroprusside (SNAP); with forskolin (an activator of
      adenylyl cyclase); or with thapsigargin (a selective inhibitor of the
      sarcoplasmic reticulum (SR), Ca2+-ATPase); and compared their apoptosis-promoting
      effects in SMC derived from the two strains of rats. SMC were derived from the
      thoracic aorta of 3-4-week-old WKY and SHR, and were used in passages 7-10.
      Apoptotic cells were detected by in-situ end labeling using the terminal
      deoxynucleotide transferase-mediated dUTP-nick end-labeling (TUNEL) method, and
      by morphological examination. We found that: 1) Treatment of cultured aortic SMC
      with the L-type Ca2+ channel antagonist, nifedipine (5 X 10(-5) M) for 24 hours
      induced a significantly higher level of apoptosis in SHR cells than in SMC from
      WKY. Cells from WKY, following exposure to nifedipine for 72 hours, exhibited a
      similar response to the cells from SHR treated for 24 hours. This was detectable
      by both morphological criteria as well as DNA labeling by the TUNEL technique. 2)
      Similar treatment of these cells with thapsigargin (1 x 10(-7) M) led to
      morphological alterations characteristic of apoptotic cells in SMC from both WKY
      and SHR, and cells from SHR but not WKY were labeled by the TUNEL technique at 24
      hours. The TUNEL method did however identify cells from both WKY and SHR as
      apoptotic after 48 and 72 hours of treatment. 3) The addition of SNAP, or
      forskolin to the cultured SMC induced significant, but low levels of apoptosis in
      WKY SMC only. This selective apoptosis-promoting effect of nifedipine in SHR SMC
      may result from differences in the control of intracellular Ca2+ between the two
      strains of cells, or it may indicate that the signaling pathways which regulate
      apoptosis are different in SMC from the normotensive and the hypertensive rats.
      Our findings imply that SMC apoptosis may be a selective target for
      pharmacological intervention in hypertension.

PMID- 10946850
TI  - Analgesic effects of endomorphin-1 and endomorphin-2 in the formalin test in
      mice.
AB  - Two recently isolated peptides, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and
      endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), are highly selective micro-opioid receptor
      agonists with analgesic actions in the tail-flick test. To further assess the
      analgesic properties of these peptides, the effects of endomorphin-1, endomorphin
      2, and morphine were examined in the formalin test. Male Swiss Webster mice were
      injected i.c.v. with endomorphin-1, endomorphin-2, or morphine (0, 1, 3, 10
      microg) 5 min before injection of 20 microl of 5% formalin s.c. into the plantar
      surface of one hind-paw. The mice were observed for 60 min after formalin
      injection. Endomorphin-1 and endomorphin-2 produced dose-dependent analgesia that
      was shorter in duration than for morphine. Increased locomotion was observed
      after morphine, but not after endomorphin-1 or endomorphin-2. These findings
      extend previous results and suggest that endomorphins may have therapeutic
      potential for the treatment of acute pain.

PMID- 10946851
TI  - The effects of delta agonists on locomotor activity in habituated and non
      habituated rats.
AB  - The effects of the delta agonists SNC80 and deltorphin II on ambulation and
      rearing activity were measured in habituated and non-habituated rats. SNC80 (30,
      100, 200, 400 nmol, i.c.v.) and deltorphin II (3, 15, 30, 60 nmol, i.c.v.)
      induced similar, dose-dependent biphasic locomotor effects in non-habituated
      subjects. An initial decrease in exploratory activity was associated with
      anxiogenic signs such as pilo-erection, freezing behaviour and pupil dilation for
      each drug. Pre-treatment with the delta antagonist naltrindole (10 nmol, i.c.v.)
      inhibited the depressant effect, but not the subsequent stimulant effect, on
      locomotor activity in response to 30 nmol deltorphin II in this assay (P<0.05).
      In habituated rats, deltorphin II (0.03, 0.1, 0.3, 3 nmol, i.c.v.) caused
      significant, naltrindole-reversible increases in locomotor activity (P<0.05 for
      all doses) at 1,000-fold lower doses than those required for a similar response
      to SNC80 (10, 30, 100, 300 nmol, i.c.v.). Pharmacokinetic studies suggest that
      these compounds penetrate the brain to similar extents following i.c.v.
      injection. The substantial potency difference between deltorphin II and SNC80 in
      stimulating locomotor activity in habituated rats suggests pharmacological
      heterogeneity for these delta opioid receptor agonists.

PMID- 10946852
TI  - Differential gene expression in nasopharyngeal carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer among southern Chinese. The
      profile of gene expression in NPC cells is largely unknown. In this study, we
      have examined differential gene expression in non-malignant and malignant
      nasopharyngeal epithelial (NPE) cells using a cDNA array hybridization method. A
      total of 42 genes were identified to be expressed in either non-malignant and
      malignant NPE cells or both. Thirteen of these genes were overexpressed in
      malignant NPE cells. These includes nuclear factor (NF90), FOS-related antigen 1
      (FRA- 1), cytoplasmic dynein light chain (HDLC1), replication factor C (RFC1),
      nucleoside diphosphate kinase B, UV excision repair protein (RAD23A), insulin
      like growth factor receptor II, transcription initiation factor TFIID subunit
      (TAFII31), growth factor receptor-bound protein 2 (GRB2), UV excision repair
      protein (RAD23B), glutathione peroxidase, Y box binding protein 1 and heat shock
      protein 86. In contrast, expression of nine genes was suppressed in malignant NPE
      cells. These includes calgranulin A, calgranulin B, neutrophil activating protein
      (ENA-78), heat shock protein 27, integrin beta-1, integrin beta-4, cyclin
      dependent kinase inhibitor 1A (p21), interleukin-8 and tyrosine protein kinase
      receptor (RET). Differential expression of calgranulin A, calgraunlin B, ENA-78,
      FRA-1 and NF90 in non-malignant and malignant nasopharyngeal epithelial cells was
      confirmed by RT-PCR analysis.

PMID- 10946853
TI  - The antiplatelet activity of tetramethylpyrazine is mediated through activation
      of NO synthase.
AB  - Tetramethylpyrazine (TMPZ) is an active ingredient of a Chinese herbal medicine
      (Ligusticum wallichii Franchat). In this study, TMPZ (50-200 microM)
      significantly increased production of nitrate and cyclic GMP in human platelets
      within a 15-min incubation period. TMPZ concentration-dependently inhibited
      intracellular Ca2+ mobilization in human platelets stimulated by collagen (5
      microg/ml). Furthermore, TMPZ concentration (50 and 200 microM)- and time (15 and
      30 min)-dependently triggered endothelial-type constitutive nitric oxide synthase
      (ecNOS) protein expression in human platelets. These results indicated that TMPZ
      at micromolar concentrations stimulated nitric oxide production in human
      platelets via a novel mechanism that activated ecNOS protein expression.

PMID- 10946854
TI  - The impact of diets with different magnesium contents on magnesium and calcium in
      serum and tissues of the rat.
AB  - The impact of three different magnesium diets (70, 1,000 and 9,000 ppm) on total,
      ionized and bound magnesium as well as ionized calcium in serum and total calcium
      and magnesium in femoral bone, skeletal muscle, heart and liver of male Sprague
      Dawley rats was investigated. The percentage of ionized serum magnesium was
      unproportionally high in rats fed a low magnesium (70 ppm) diet. Femoral
      magnesium was correlated with ionized and total serum magnesium. In contrast,
      there was generally no correlation between total serum magnesium and the
      magnesium fractions in skeletal muscle, heart and liver. In rats fed the
      magnesium deficient diet, total cardiac concentration of magnesium was even
      significantly increased along with total calcium content, while there were no
      effects on total muscle and liver magnesium. Within the single groups, ionized
      serum calcium was never proportional to dietary magnesium, but in all three
      magnesium diet groups together, it was inversely correlated with dietary
      magnesium. Moreover, ionized serum calcium was inversely correlated with both
      ionized and total serum magnesium. In all 3 groups together, the concentrations
      of total calcium and magnesium in heart and skeletal muscle were correlated,
      within the single groups correlation existed only in the 1000 ppm group.
      Magnesium influx via calcium channels during low magnesium intake has been seen
      in non cardiac tissues [35,36], but nothing similar is known about non selective
      channels for divalent cations in the heart [33]. Thus, magnesium uptake by
      cardiac cells along with calcium seems to be possible, especially at low
      intracellular magnesium concentrations, but is still poorly investigated. We
      suggest that the calcium-antagonistic effect of magnesium is related to the
      turnover rate of magnesium rather than to its tissue concentrations.

PMID- 10946855
TI  - Chronic changes in plasma triglyceride levels do modify platelet membrane
      microviscosity in rats.
AB  - Lipid metabolism disorders were proposed to mediate numerous cell membrane
      alterations in various forms of hypertension. Elevated plasma triglycerides were
      found to be associated with changes in membrane structure and function related to
      altered microviscosity in particular domains of the cell membrane. The aim of our
      study was to determine if an abnormal triglyceride metabolism might play a causal
      role in these alterations of membrane dynamics. Using genetically hypertensive
      rats of the Prague hereditary hypertriglyceridemic (HTG) strain we investigated
      whether the elevation of circulating triglycerides induced by high fructose
      intake and/or their lowering by chronic gemfibrozil treatment (for 10 weeks
      starting at the age of 6 weeks) are followed by reciprocal changes in membrane
      microviscosity. Two different fluorescent probes exploring either the outer
      membrane leaflet (TMA-DPH anisotropy) or the membrane lipid core (DPH anisotropy)
      were used in platelets of HTG rats. DPH (diphenylhexatriene) fluorescence
      anisotropy was decreased in platelets of fructose-treated HTG animals with highly
      elevated plasma triglyceride levels, whereas it was increased in gemfibrozil
      treated HTG rats in which triglyceride levels were almost normalized. On the
      contrary, TMA-DPH (trimethylamino-diphenylhexatriene) anisotropy was not
      substantially altered in platelets from HTG rats by the above modifications of
      circulating triglycerides. No changes of plasma cholesterol or blood pressure
      were associated with the triglyceride-dependent modifications of membrane core
      microviscosity. Our interventional study demonstrates a major causal role of
      circulating triglycerides in the control of the microviscosity of membrane lipid
      core.

PMID- 10946856
TI  - Evidence that ginsenosides prevent the development of opioid tolerance at the
      central nervous system.
AB  - The analgesic effect of ginsenosides or morphine was first determined following
      intrathecal (i.t.) administration in rat tail-flick test. The effect of chronic
      i.t. co-administration of ginsenosides with morphine on the development of opioid
      tolerance were also examined using rat tail-flick test. Administration of
      ginsenosides (i.t.) produced a weak antinociception in a dose-dependent manner.
      Administration of morphine (i.t.) also produced antinociception in a dose
      dependent manner. The ED50 was 1.20 microg (1.14-1.29 microg). However, acute
      i.t. co-administration of ginsenosides with morphine was not additive in
      antinociception. Repeated i.t. co-administration of 200 microg ginsenosides with
      10 microg morphine inhibited the development of tolerance induced by 10 microg
      morphine in rat tail-flick test, although i.t. co-administration of 50 or 100
      microg ginsenosides with morphine was without effect. In conclusion, these
      results indicate that i.t. administered ginsenosides produce an antinociception
      in rat tail-flick test and also prevent opioid tolerance caused by chronic
      treatment with morphine at the spinal sites.

PMID- 10946857
TI  - Validation of urea as an endogenous reference compound for the in vivo
      calibration of microdialysis probes.
AB  - Microdialysis is a widely used experimental technique, which offers the
      opportunity to measure drug and metabolite concentrations in the interstitial
      space fluid in animals and humans. However, microdialysis probes need to be
      calibrated in vivo to obtain a recovery factor, which describes the relative drug
      transfer across the membrane. Recently, novel time-saving calibration techniques,
      based on the use of reference compounds, have been developed. In particular, the
      use of endogenous urea levels has been advocated. In the present study we set out
      to validate the use of the urea reference technique for microdialysis probe
      calibration in healthy volunteers, employing glucose and paracetamol as model
      analytes. Urea calibration was compared with the results of two standard
      calibration techniques, i.e. the no net flux technique and the retrodialysis
      technique. For glucose, recovery values, calculated by the urea reference
      technique differed significantly from those values, which were assessed by the no
      net flux technique (p < 0.05), whereas for paracetamol recovery values did not
      differ significantly, albeit a high intramethod variability was observed
      (CV=66%). As a conclusion, we could not confirm the hypothesis that recovery
      values calculated by the urea reference technique provide equivalent results
      compared with standard calibration techniques.

PMID- 10946858
TI  - Thyrotropin receptor polymorphisms and thyroid diseases.

PMID- 10946859
TI  - Lack of association of nonautoimmune hyperfunctioning thyroid disorders and a
      germline polymorphism of codon 727 of the human thyrotropin receptor in a
      European Caucasian population.
AB  - Constitutively activating mutations of the human TSH receptor (hTSHR) gene have
      been implicated as a major cause of hyperfunctioning nonautoimmune thyroid
      disease. However, significant geographic differences in the prevalence of these
      mutations have been observed. Recently, a high frequency of a germline
      polymorphism at codon 727 of the cytoplasmic tail of the hTSHR has been
      demonstrated in patients with toxic multinodular goiter. In the present study we
      assessed whether the codon 727 polymorphism is associated with hyperfunctioning
      thyroid adenomas. PCR followed by restriction enzyme digestion were used to
      genotype a total of 128 European Caucasian patients with toxic nonautoimmune
      thyroid disease (83 with toxic adenoma, 31 with toxic multinodular goiter, and 14
      with disseminated autonomy) and to compare their codon 727 polymorphism
      frequencies with those of 99 healthy controls and 108 patients with Graves'
      disease. All individuals were drawn from an identical ethnic background.
      Sequencing of PCR products was used to confirm the mutation analysis. We found no
      significant differences in codon 727 polymorphism frequencies between patients
      with autonomously functioning thyroid disorders (13.3%) and the healthy control
      group (16.2%; P = 0.57). Moreover, the subtypes of toxic nonautoimmune thyroid
      disease (toxic adenoma, 13.2%; multinodular goiter, 9.6%; disseminated autonomy,
      21.4%) were not related to significant differences in codon 727 polymorphism
      frequencies compared with the healthy control group (P = 0.67, P = 0.40, and P =
      0.70, respectively). Additionally, there were no significant differences between
      patients with Graves' disease (21.3%) and healthy controls (P = 0.38). In
      conclusion, our data do not support an association between the codon 727
      polymorphism of the hTSHR and toxic thyroid adenomas or toxic multinodular goiter
      in our study population. Thus, the codon 727 polymorphism of the hTSHR does not
      appear to be involved in the evolution of autoimmune or nonautoimmune
      hyperthyroidism in the European Caucasian population.

PMID- 10946860
TI  - Triple H syndrome: a novel autoimmune endocrinopathy characterized by dysfunction
      of the hippocampus, hair follicle, and hypothalamic-pituitary adrenal axis.

PMID- 10946861
TI  - Oral estradiol administration modulates continuous intravenous growth hormone
      (GH)-releasing peptide-2-driven GH secretion in postmenopausal women.
AB  - Exactly how estradiol (E2) regulates the human GH-insulin-like growth factor I
      axis is not known. Here, we explore the impact of oral E2 supplementation on the
      stimulatory actions of a potent and specific synthetic GH-releasing peptide
      (GHRP), GHRP-2. To this end, we studied 10 healthy postmenopausal women following
      the administration of placebo or 17beta-estradiol (1 mg twice daily orally) for 7
      12 days in a prospectively randomized, double-blind, within-subject crossover
      design. To drive GH secretion via the GHRP-receptor/ effector pathway, we infused
      GHRP-2 (1 microg/kg x h) or saline continuously iv for 24 h. Deconvolution
      analysis was used to quantitate the separate basal and pulsatile modes of GH
      secretion based on 24-h serum GH concentrations profiles collected at 10-min
      intervals and assayed by chemiluminescence. As complementary (nonpulsatile)
      measures, we used the approximate entropy (ApEn) statistic and cosine regression
      to define feedback-dependent and circadian-related changes, respectively. E2
      administration amplified the mass of GH secreted per burst by 1.9-fold over
      placebo, 24-h GHRP-2 infusion by 7.0-fold, and, the two agonists together by 8.8
      fold (P < 10(-14)). Intravenous GHRP-2 infusion augmented the basal
      (nonpulsatile) rate of GH secretion by 4.4-fold (P < 10(-4)). E2 treatment had no
      effect alone, but doubled the stimulatory effect of GHRP-2, on basal GH
      secretion. Neither E2 nor GHRP-2 influenced 24-h GH pulse frequency, interburst
      interval, half-life or pulse duration. Combined E2 and GHRP-2 elevated the ApEn
      of GH secretory profiles significantly above control, thereby indicating a marked
      alteration of within-axis feedback control (P = 0.00033). Dual stimulation with
      E2 and GHRP-2 also synergistically increased the amplitude (by 11-fold, P < 10(
      11)) and the mesor (by 10-fold, P < 10(-10)) of the 24-h GH rhythm. Infusion of
      GHRP-2 advanced the GH acrophase (time of daily maximum of GH release) by 8.75 h,
      whereas combined treatment with E2 and GHRP-2 normalized the acrophase. Cross
      correlation analysis showed that GHRP-2 infusion (but not E2 administration)
      significantly synchronized paired 24-h serum GH concentration profiles (P < 10(
      3)). In summary, short-term oral E2 replacement in post-menopausal women strongly
      modulates the actions of a synthetic hexapeptide GH secretagogue on three
      quantifiable modes of GH secretion [i.e. 1) basal (nonpulsatile) GH release; 2)
      feedback-dependent ApEn; and 3) the mesor, amplitude and timing of the 24-h GH
      rhythm]. Moreover, a continuous GHRP-2 stimulus also synchronizes inter diem GH
      secretory patterns. The present pharmacological study, thus, offers a further
      framework for exploring the nature of the interactions of E2 with the GHRP
      receptor/effector pathway in the aging and/or gonadoprival human.

PMID- 10946862
TI  - Hypothalamic-pituitary-adrenal axis activity during exercise in African American
      and Caucasian women.
AB  - African American women have a greater prevalence of obesity than Caucasian women,
      but the reasons for this difference are not known. We have investigated whether
      activity of the hypothalamic-pituitary adrenal axis plays a role in this
      phenomenon. Previous studies have shown that plasma ACTH immunoreactivity (ACTH
      IR) of African American women, measured after ovine CRH (oCRH) stimulation, is
      significantly greater than ACTH-IR of Caucasian women, but is not accompanied by
      greater plasma cortisol concentrations. Analysis by high pressure liquid
      chromatography has demonstrated that after oCRH stimulation, the plasma ACTH-IR
      of African American women contains many nonintact ACTH fragments not found in
      Caucasians. To determine whether these racial differences in ACTH-IR secretion
      are an artifact of exogenous oCRH administration or are also found after a
      physiological stimulus for ACTH secretion, we measured hormones of the
      hypothalamic-pituitary adrenal axis before and after a standardized, maximal
      exercise treadmill test in 16 African American and 19 Caucasian healthy women
      matched for age, socioeconomic status, and body mass index. The intensity of
      exercise performed was similar in the two groups, as determined by duration of
      exercise, perceived intensity of exertion, plasma lactate, maximal heart rate,
      and maximum oxygen uptake. Basal ACTH-IR measured by RIA or immunoradiometric
      assay and cortisol were similar in African Americans and Caucasians. Plasma ACTH
      IR, measured 10 min after completion of exercise, was significantly greater in
      African Americans than in Caucasians [by RIA: mean +/- SD ACTH-IR, 47.1 +/- 30.9
      vs. 25.4 +/- 16.7 pmol/L (P < 0.01); by immunoradiometric assay: ACTH-IR, 45.9 +/
      43.2 vs. 21.1 +/- 14.6 pmol/L (P < 0.05)]. However, plasma cortisol after
      exercise was not different (450.2 +/- 157.7 vs. 483.6 +/- 180.4 nmol/L; P =
      0.57). We conclude that ACTH-IR is significantly greater in African American than
      in Caucasian women after intense exercise. The ACTH-IR of African Americans and
      Caucasians does not appear to be equipotent at adrenal melanocortin-2 receptors,
      because the greater ACTH-IR of African Americans does not lead to greater
      cortisol secretion. Whether some components of the ACTH-IR detected in African
      Americans affect signal transduction of the hypothalamic melanocortin-4 receptors
      implicated in body weight regulation and thus predispose African American women
      to weight gain without altering plasma cortisol remains to be determined.

PMID- 10946863
TI  - Complete androgen insensitivity syndrome: long-term medical, surgical, and
      psychosexual outcome.
AB  - Controversy concerning the most appropriate treatment guidelines for intersex
      children currently exists. This is due to a lack of long-term information
      regarding medical, surgical, and psychosexual outcome in affected adults. We have
      assessed by questionnaire and medical examination the physical and psychosexual
      status of 14 women with documented complete androgen insensitivity syndrome
      (CAIS). We have also determined participant knowledge of CAIS as well as opinion
      of medical and surgical treatment. As a whole, secondary sexual development of
      these women was satisfactory, as judged by both participants and physicians. In
      general, most women were satisfied with their psychosexual development and sexual
      function. Factors reported to contribute to dissatisfaction were sexual abuse in
      one case and marked obesity in another. All of the women who participated were
      satisfied with having been raised as females, and none desired a gender
      reassignment. Although not perfect, the medical, surgical, and psychosexual
      outcomes for women with CAIS were satisfactory; however, specific ways for
      improving long-term treatment of this population were identified.

PMID- 10946864
TI  - Effects of testosterone replacement in hypogonadal men.
AB  - Treatment of hypogonadal men with testosterone has been shown to ameliorate the
      effects of testosterone deficiency on bone, muscle, erythropoiesis, and the
      prostate. Most previous studies, however, have employed somewhat pharmacological
      doses of testosterone esters, which could result in exaggerated effects, and/or
      have been of relatively short duration or employed previously treated men, which
      could result in dampened effects. The goal of this study was to determine the
      magnitude and time course of the effects of physiological testosterone
      replacement for 3 yr on bone density, muscle mass and strength, erythropoiesis,
      prostate volume, energy, sexual function, and lipids in previously untreated
      hypogonadal men. We selected 18 men who were hypogonadal (mean serum testosterone
      +/- SD, 78 +/- 77 ng/dL; 2.7 +/- 2.7 nmol/L) due to organic disease and had never
      previously been treated for hypogonadism. We treated them with testosterone
      transdermally for 3 yr. Sixteen men completed 12 months of the protocol, and 14
      men completed 36 months. The mean serum testosterone concentration reached the
      normal range by 3 months of treatment and remained there for the duration of
      treatment. Bone mineral density of the lumbar spine (L2-L4) increased by 7.7 +/-
      7.6% (P < 0.001), and that of the femoral trochanter increased by 4.0 +/- 5.4% (P
      = 0.02); both reached maximum values by 24 months. Fat-free mass increased 3.1 kg
      (P = 0.004), and fat-free mass of the arms and legs individually increased,
      principally within the first 6 months. The decrease in fat mass was not
      statistically significant. Strength of knee flexion and extension did not change.
      Hematocrit increased dramatically, from mildly anemic (38.0 +/- 3.0%) to
      midnormal (43.1 +/- 4.0%; P = 0.002) within 3 months, and remained at that level
      for the duration of treatment. Prostate volume also increased dramatically, from
      subnormal (12.0 +/- 6.0 mL) before treatment to normal (22.4 +/- 8.4 mL; P =
      0.004), principally during the first 6 months. Self-reported sense of energy (49
      +/- 19% to 66 +/- 24%; P = 0.01) and sexual function (24 +/- 20% to 66 +/- 24%; P
      < 0.001) also increased, principally within the first 3 months. Lipids did not
      change. We conclude from this study that replacing testosterone in hypogonadal
      men increases bone mineral density of the spine and hip, fat-free mass, prostate
      volume, erythropoiesis, energy, and sexual function. The full effect of
      testosterone on bone mineral density took 24 months, but the full effects on the
      other tissues took only 3-6 months. These results provide the basis for
      monitoring the magnitude and the time course of the effects of testosterone
      replacement in hypogonadal men.

PMID- 10946865
TI  - Leptin production in adipocytes from morbidly obese subjects: stimulation by
      dexamethasone, inhibition with troglitazone, and influence of gender.
AB  - This study examined the regulation of leptin production by dexamethasone and
      troglitazone. Subcutaneous and omental adipose tissue was obtained during
      bariatric surgical procedures (30 women and 16 men; body mass index, 52.5 +/- 1.7
      kg/m2, age, 39 +/- 2 yr), and adipocytes were cultured in suspension.
      Subcutaneous adipocytes from females released significantly more leptin than did
      omental cells from the same subject (P < 0.05), but basal leptin release was not
      different in adipocytes from these depots in males. Dexamethasone (0.1
      micromol/L) significantly increased leptin release within 24 h from sc (135 +/-
      13% of control) and omental (227 +/- 53%) adipocytes of females, but not males.
      Dexamethasone-stimulated leptin production at 48 h was significantly greater in
      the omental adipocytes of females (398 +/- 64% of control) than in sc adipocytes
      of females (207 +/- 21%) or the omental (211 +/- 33%) and sc (180 +/- 23%)
      adipocytes of males. Troglitazone (10 micromol/L; 48 h) significantly inhibited
      dexamethasone-stimulated leptin release in sc (57 +/- 10.7% inhibition) and
      omental adipocytes (134 +/- 26% inhibition). There was no gender-related
      difference in the effect of troglitazone to inhibit dexamethasone-stimulated
      leptin release. Troglitazone significantly inhibited basal leptin production from
      omental adipocytes by 15.0 +/- 5.2%. The effect of dexamethasone and troglitazone
      to regulate leptin release was mediated through changes in ob gene expression,
      but did not involve changes in glucose uptake or metabolism to lactate. The data
      suggest that adipocytes from females are more responsive to the stimulatory
      effect of dexamethasone in vitro than are adipocytes from males. If adipocytes
      from females are more responsive to relevant in vivo stimuli for leptin secretion
      such as insulin or glucose, this could contribute to the gender difference in
      serum leptin. The data also suggest that leptin release from omental adipocytes
      may be more responsive to hormonal and nutrient regulation in vivo than are sc
      adipocytes.

PMID- 10946866
TI  - Twenty-four-hour leptin levels respond to cumulative short-term energy imbalance
      and predict subsequent intake.
AB  - Leptin plays a vital role in the regulation of energy balance in rodent models of
      obesity. However, less information is available about its homeostatic role in
      humans. The aim of this study was to determine whether leptin serves as an
      indicator of short-term energy balance by measuring acute effects of small
      manipulations in energy intake on leptin levels in normal individuals. The 12-day
      study was composed of four consecutive dietary-treatment periods of 3 days each.
      Baseline (BASE) [100% total energy expenditure (TEE)] feeding, followed by random
      crossover periods of overfeeding (130% TEE) or underfeeding (70% TEE) separated
      by a eucaloric (100% TEE) washout (WASH) period. The study participants were six
      healthy, nonobese subjects. Leptin levels serially measured throughout the study
      period allowed a daily profile for each treatment period to be constructed and a
      24-h average to be calculated; ad libitum intake during breakfast "buffet"
      following each treatment period was also measured. Average changes in mesor
      leptin levels during WASH, which were sensitive to energy balance effected during
      the prior period, were observed. After underfeeding, leptin levels during WASH
      were 88 +/- 16% of those during BASE compared with 135 +/- 22% following
      overfeeding (P = 0.03). Leptin levels did not return to BASE during WASH when
      intake returned to 100% TEE, but instead were restored (104 +/- 21% and 106 +/-
      16%; not significant) only after subjects crossed-over to complementary dietary
      treatment that restored cumulative energy balance. Changes in ad libitum intake
      from BASE correlated with changes in leptin levels (r2 = 0.40; P = 0.01). Leptin
      levels are acutely responsive to modest changes in energy balance. Because leptin
      levels returned to BASE only after completion of a complementary feeding period
      and restoration of cumulative energy balance, leptin levels reflect short-term
      cumulative energy balance. Leptin seems to maintain cumulative energy balance by
      modulating energy intake.

PMID- 10946867
TI  - Fas and Fas ligand expression in fetal and adult human testis with normal or
      deranged spermatogenesis.
AB  - In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ
      cell apoptosis. In the present study we evaluated the expression of Fas and Fas
      ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR
      demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult
      testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and
      immunohistochemistry experiments on adult human testis demonstrated the
      expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig
      cells, whereas the expression of Fas was confined to the Leydig cells and
      sporadic degenerating spermatocytes. The number of Fas-positive germ cells per
      100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell
      arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/-
      0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean,
      1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic
      hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL
      expression in the human testis is developmentally regulated and under
      gonadotropin control. The increased germ cell expression of Fas in patients with
      postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in
      the quality control mechanism of the produced gametes.

PMID- 10946869
TI  - Analysis of thyrotropin-releasing hormone-signaling components in pituitary
      adenomas of patients with acromegaly.
AB  - In many acromegalic patients the paradoxical release of GH in response to TRH has
      been well documented, but the mechanisms underlying this phenomenon are not
      understood. It has been suggested that aberrant GH secretion may result from TRH
      endogenously synthesized by the adenoma. In 32 adenomas from acromegalic
      patients, TRH-like immunoreactivity (TRH-LI) was measured using 2 well
      characterized antisera. TRH-LI was not detectable in 10 samples, and in 19
      samples, TRH-LI was measured only by the less specific antibody. With the TRH
      specific antibody, TRH-LI was identified only in 3 samples, 2 of which contained
      exceedingly high concentrations (40 and 96 pg/mg tissue). In the latter 2
      samples, prepro-TRH messenger ribonucleic acid was identified by Northern blot
      analysis, but not in the control tissue sample of a patient without pituitary
      disease and also not in the other adenomas analyzed by this technique.
      Transcripts of the TRH receptor were almost undetectable in all adenomas
      analyzed. For the TRH-degrading ectoenzyme, a potential regulator of TRH signals
      at adenohypophyseal target sites, transcripts were significantly expressed only
      in the TRH-producing adenomas. We conclude that the TRH-signaling elements
      examined are, in general, not directly involved in the mechanisms causing
      paradoxical GH secretion in acromegalic patients.

PMID- 10946868
TI  - Molecular analysis of LHX3 and PROP-1 in pituitary hormone deficiency patients
      with posterior pituitary ectopia.
AB  - The cause of posterior pituitary ectopia associated with anterior pituitary
      hormone deficiencies is unknown. We describe children with combined pituitary
      hormone deficiency (CPHD) or isolated GH deficiency. In all cases, magnetic
      resonance imaging examination revealed abnormal pituitary gland development
      featuring ectopic posterior lobe location and frequently hypoplastic anterior
      lobes. Embryonic development of the pituitary requires the coordinated expression
      of specific transcription factors. Mutations of the PIT-1 and PROP-1
      transcription factors are responsible for CPHD in some patients with normally
      positioned posterior pituitaries. In mice, the Lhx3 LIM homeodomain transcription
      factor is required for both structural development and cellular differentiation
      of the pituitary gland. Thus, we hypothesized that mutations in one or both of
      the two human LHX3 isoforms are responsible for posterior pituitary ectopia
      associated with anterior pituitary hypopituitarism. Comprehensive molecular
      analysis of the LHX3 isoforms was performed to test this hypothesis. No loss of
      function mutations in the LHX3 gene were detected. In addition, analysis of PROP
      1 did not reveal mutations that might cause this phenotype. These studies suggest
      that the abnormal processes leading to the development of CPHD or GH deficiency
      associated with posterior pituitary ectopia are not a result of aberrant LHX3 or
      PROP- 1 function, but may be caused by defects at other gene loci.

PMID- 10946870
TI  - Regulation of insulin-like growth factor-binding protein-1 by nitric oxide under
      hypoxic conditions.
AB  - Nitric oxide (NO) is believed to play an important, but as yet undefined, role in
      regulating hypoxia inducible gene expression. Recently, we have reported evidence
      suggesting that the human insulin-like growth factor-binding protein-1 (IGFBP-1)
      gene is directly regulated by hypoxia through the hypoxia-inducible factor-1
      pathway. The goal of the current study was to investigate NO regulation of
      hypoxic induction of IGFBP-1 gene expression using HepG2 cells, a model system of
      hepatic gene expression. We report that a NO generator, sodium nitroprusside,
      significantly diminishes hypoxic activation of IGFBP-1 protein and messenger
      ribonucleic acid expression. Furthermore, these effects are independent of
      guanylate cyclase/ cGMP signaling, as two different inhibitors, LY 83583, a
      specific inhibitor of guanylate cyclase, and KT 5823, a protein kinase G
      inhibitor, had no effect on IGFBP-1 induction by hypoxia. Hypoxic induction of a
      reporter gene containing four tandemly ligated hypoxia response elements was
      completely blocked by sodium nitroprusside, but not by 8-bromo-cGMP, an analog
      ofcGMP. These results suggest that NO blocks hypoxic induction of IGFBP-1 by a
      guanylate cyclase/ cGMP-independent pathway, possibly at the level of oxygen
      sensing. The impaired hypoxia regulation of IGFBP-1 by nitric oxide may play a
      key role in the hyperinduction of IGFBP-1 observed in pathophysiological
      conditions such as fetal hypoxia and preeclampsia where dysregulation of NO has
      been observed.

PMID- 10946871
TI  - The hypothalamic-pituitary-thyroid negative feedback control axis in children
      with treated congenital hypothyroidism.
AB  - Measurements of serum concentrations of free T4, T3, TSH, and thyroglobulin (Tg)
      were conducted in 42 infants (2-9 months of age) detected and treated through the
      Northwest Newborn Regional Screening Program and 63 children and adolescents (1
      18 yr of age) with congenital hypothyroidism (CH) detected and managed in the
      Northern California Kaiser Permanente Medical Care Program. Normal feedback
      control axis data were developed by Quest Diagnostics, Inc. - Nichols Institute
      Diagnostics and Loma Linda University, from free T4 and TSH measurements in 589
      healthy subjects, 2 months to 54 yr of age; 83 untreated hypothyroid patients;
      and 116 untreated hyperthyroid patients. Twenty-four of the 42 CH infants and 57
      of the 63 CH children manifested serum TSH concentrations appropriate for the
      measured free T4 level. In the remaining 18 infants and 6 children, serum free T4
      values were increased 0.2-1.4 ng/dL (2.6-18.0 pmol/L) for the prevailing TSH
      level, suggesting a state of mild to moderate pituitary-thyroid hormone
      resistance. In the treated children, the mean T3 concentration was lower (by 32%,
      102 vs. 150 ng/dL; 1.57 vs. 2.31 nmol/L) than in normal children, in agreement
      with earlier data in hypothyroid adults treated with exogenous T4. Serum Tg
      concentrations were normal or elevated in 90% of the 19 children with ectopic
      glands and 93% of 27 children with eutopic glands in whom measurements were
      available. There was a positive correlation between serum TSH and Tg
      concentrations (P < 0.001), suggesting significant endogenous thyroid hormone
      production in these children. Our results suggest that the majority of infants
      and children with CH have a normal hypothalamic-pituitary-thyroid negative
      feedback control axis during treatment and that the measurement of serum TSH is a
      useful marker complementing the free T4 measurement in the management of children
      with CH. A minority have variable pituitary-thyroid hormone resistance, with
      relatively elevated serum TSH levels for their prevailing serum free T4
      concentration. The prevalence of resistance is greater (43%) in young infants (<
      1 yr of age) than in older children (10%), indicating that, in most children, the
      resistance improves with age.

PMID- 10946872
TI  - Serum soluble tumor necrosis factor-alpha receptor 2 is elevated in obesity but
      is not related to insulin sensitivity: a study in identical twins discordant for
      obesity.
AB  - Tumor necrosis factor-alpha (TNFalpha) and its soluble receptor 2 (TNFR2) are
      expressed in adipose tissue and are possibly involved in the pathogenesis of
      insulin resistance. Information about serum levels of TNFR2 in human obesity,
      especially the possible role of genetic factors and body fat distribution, is
      scanty. We measured serum TNFalpha and soluble TNFR2 concentrations in 23
      identical twin pairs who had an average 18-kg intrapair difference in body
      weight. The mean TNFalpha concentration was 44.1 ng/L in obese and 34.2 ng/L in
      lean cotwins (P = 0.051). The respective values for TNFR2 were 1,989 and 1,840
      ng/L (P = 0.004). The intrapair difference in TNFR2 level correlated positively
      (r-value always > or = 0.56; P < or = 0.01) with intrapair differences in body
      mass index, percent body fat, and abdominal sc fat area (assessed by magnetic
      resonance imaging), but not with differences in visceral fat area, glucose or
      insulin areas under the curve, or insulin sensitivity index in the oral glucose
      tolerance test. The intraclass correlation for TNFR2 was 0.67, and the genetic
      variation in circulating TNFR2 level was almost 6-fold higher than the variation
      due to obesity. We conclude that the soluble TNFR2 concentration is determined by
      both genetic factors and adiposity, especially sc fat. Measurement of circulating
      TNFR2 does not seem to be useful in identifying obese individuals who are insulin
      resistant.

PMID- 10946873
TI  - Prevalence and distribution of ret/ptc 1, 2, and 3 in papillary thyroid carcinoma
      in New Caledonia and Australia.
AB  - The world's highest incidence of thyroid cancer has been reported among females
      in New Caledonia, a French overseas territory in the Pacific located between
      Australia and Fiji. To date, no molecular genetic studies in this population are
      available. Over the past few years, the oncogenic rearrangement of the ret
      protooncogene (ret/ptc) has been studied in papillary carcinomas in different
      populations. In this study, we investigated the prevalence and distribution of
      ret/ptc1, 2, and 3 in papillary thyroid carcinoma from the New Caledonian
      population and compared the pattern with that of an Australian population. Fresh
      frozen and paraffin-embedded papillary carcinomas from 27 New Caledonian and 20
      Australian patients were examined for ret rearrangements by means of RT-PCR with
      primers flanking the chimeric region, followed by hybridization with radioactive
      probes. ret/ptc was present in 70% of the New Caledonian and in 85% of the
      Australian samples. Multiple rearrangements were detected and confirmed by
      sequencing in 19 cases, 4 of which had 3 types of rearrangements in the same
      tumor. This study demonstrates a high prevalence of ret/ptc in New Caledonian and
      Australian papillary carcinoma. The findings of multiple ret/ptc in the same
      tumor suggest that some thyroid neoplasms may indeed be polyclonal.

PMID- 10946874
TI  - Does growth hormone (GH) enhance growth in GH-deficient children with
      myelomeningocele?
AB  - GH deficiency (GHD) in patients with myelomeningocele leads to the question of
      whether these disabled patients should be treated with human GH. To date, only a
      few short-term reports of GH therapy are available in the literature, and long
      term data for final height are lacking. We report auxological and laboratory data
      for seven prepubertal myelomeningocele patients with proven GHD (idiopathic GHD
      or neurosecretory dysfunction) during GH treatment. All patients (five males and
      two females; median chronological age, 6.6 yr) had shunted hydrocephalus and were
      treated with GH (0.5 IU/kg x week; 0.15 mg/kg x week; daily sc injections) over a
      median period of 38 months (range, 35-49 months). GH secretion was analyzed by
      measurement of spontaneous overnight GH secretion and two standard stimulation
      tests. Auxological parameters, bone age, serum levels of insulin-like growth
      factor I and insulin-like growth factor-binding protein-3, and neurological and
      orthopedic status were documented regularly. Median growth velocity of supine
      length improved during treatment (at start, 3.7 cm/yr; after 36 months, 5.7
      cm/yr; P < 0.05), with highest levels 6 months after the start of therapy (8.1
      cm/yr). The growth velocity of arm span was greater than these values. Supine
      length SD score for chronological age increased from -4.71 (at start) to -3.35
      (after 36 months; P = NS), length SD score for bone age increased from -2.70 to 
      2.23 (P = NS), and arm span SD score increased from -2.98 to -1.75 (P < 0.05).
      The growth velocities of length and arm span remained significantly above the
      pretreatment values (P < 0.05). Symptomatic tethered cord associated with
      progression of scoliosis developed in two of seven children. GH treatment
      significantly improved the growth velocities of body length and arm span.
      However, the increase in length SD score was not significant, whereas arm span SD
      scores significantly improved over the study period.

PMID- 10946876
TI  - Association of estrogen receptor-alpha genotypes with body mass index in normal
      healthy postmenopausal Caucasian women.
AB  - Several lines of evidence suggest the importance of the estrogen receptor (ER) in
      determining body mass index (BMI). Our purpose was to investigate whether genetic
      polymorphisms at the restriction enzyme PvuII site of the ER-alpha gene locus are
      associated with BMI variation. Data on BMI, age, and ER-alpha genotypes were
      obtained from 108 healthy midwestern U.S. postmenopausal Caucasian women. The
      study subjects were unrelated and aged 65 yr and over (mean age +/- SD, 73.4 +/-
      5.1 yr), with an average BMI of 25.25 (SD, 4.04). The ER-alpha genotypes were
      obtained by PCR followed by restriction enzyme PvuII digestion. We found that in
      our study subjects the ER-alpha genotypes are significantly associated with BMI
      (by ANOVA, P = 0.04), explaining about 6.2% of the BMI variation in our study
      sample. The allelic effects of this locus on BMI are approximately additive. In
      our sample, individuals of the PP and Pp genotypes have, respectively, 11.4% and
      4.8% higher BMI than individuals of the pp genotype. There is a significant ER
      alpha genotype by age interaction, so that in our sample PP individuals tend to
      gain weight with age, whereas Pp and pp individuals tend to lose weight with age.
      Therefore, the ER-alpha polymorphisms are associated with BMI variation in
      healthy postmenopausal Caucasian women aged 65 yr and over. Our result is
      consistent with some recent findings suggesting the potential effects of the ER
      on BMI. The importance of the ER-alpha genotypes in other populations and other
      age groups needs to be demonstrated. Although the results of the ER-alpha
      genotype by age interaction are obtained here from cross-sectional data, direct
      confirmation may come from longitudinal studies in which individuals are measured
      multiple times over several years. The importance of the ER-alpha genotypes on
      BMI should be confirmed by further studies using methods robust to the potential
      problem of population substructuring that may confound the conclusions of
      population association studies.

PMID- 10946875
TI  - Insulin-like growth factor I is not a useful marker of prostate cancer in men
      with elevated levels of prostate-specific antigen.
AB  - High serum levels of insulin-like growth factor I (IGF-I) and low levels of IGF
      binding protein-3 (IGFBP-3) have been shown to correlate with increased prostate
      cancer risk. To evaluate this, IGF-I, IGFBP-3, and prostate-specific antigen
      (PSA) were measured in serum from 665 consecutive men (179 with prostate cancer),
      aged 55-67 yr, with elevated serum prostate-specific antigen (PSA; > or = 4
      microg/L) in a screening trial. Men in the highest quartile of IGF-I levels had
      an odds ratio (OR) for prostate cancer of 0.50 [95% confidence interval (CI) 0.26
      0.97] when adjusting for serum IGFBP-3. IGFBP-3 itself was not significantly
      associated with prostate cancer risk (OR, 1.24; 95% CI, 0.68-2.24). Prostate
      volume was larger in men without than in those with prostate cancer (P < 0.001),
      and after adjustment for prostate volume, the negative association between serum
      IGF-I and prostate cancer risk was no longer significant (OR, 0.57; 95% CI, 0.28
      1.16). In screen-positive men with elevated serum PSA, serum IGF-I is not a
      useful diagnostic test for prostate cancer, but it may be associated with benign
      prostatic hyperplasia and enlargement.

PMID- 10946877
TI  - Chicken ovalbumin upstream promoter transcription factor II in the human adrenal
      cortex and its disorders.
AB  - Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an
      orphan member of the steroid/thyroid hormone receptor superfamily. COUP-TFII has
      been demonstrated to negatively regulate the transcriptional activity of adrenal
      4-binding protein, a steroidogenic cell-specific transcription factor that
      activates the transcription of various steroidogenic P450 genes. We therefore
      examined immunolocalization of COUP-TFII in the human adrenal cortex and its
      disorders, including functioning and nonfunctioning cortical tumors, to study its
      possible correlation with adrenocortical steroidogenesis. In nonpathological
      adrenal cortex, COUP-TFII immunoreactivity was marked in the nuclei of
      adrenocortical cells in definitive and fetal zones from 16 gestational weeks to 2
      months after birth. Immunoreactivity for COUP-TFII was marked in the zona
      glomerulosa and weak in the zonae fasciculata and reticularis from 7 months to 8
      yr of age, but thereafter markedly decreased in these zones (P < 0.05, between
      age 7 months to 8 yr and 24-62 yr of age, respectively). In adrenocortical
      tumors, COUP-TFII immunoreactivity was marked in the nuclei of tumor cells of
      aldosteroma (H score, 134 +/- 15.9; P < 0.001 vs. Cushing's adenoma and P < 0.05
      vs. nonfunctioning adenoma and carcinoma), modest in nonfunctioning adenoma (82.7
      +/- 19.8) and adrenocortical carcinoma (79.6 +/- 56.3), and low in Cushing's
      adenoma (38.2 +/- 24.5). Results from immunoblotting performed in seven cases of
      adenomas were consistent with those of immunohistochemistry. In the attached
      nonneoplastic adrenal cortex of the adenomas, immunoreactivity for COUP-TFII was
      markedly increased compared to that in nonpathological adrenal cortex in adults
      and was especially marked in the zona glomerulosa in the attached adrenal of
      aldosteroma (P < 0.001) and the zona fasciculata in that of Cushing's adenoma (P
      < 0.05). COUP-TFII immunoreactivity was universally detected in stromal cells of
      the adrenal glands. These results suggest that COUP-TFII plays an important role
      in the regulation of steroidogenesis in human adrenal cortex and its disorders.

PMID- 10946878
TI  - Impairment and recovery of elementary cognitive function induced by hypoglycemia
      in type-1 diabetic patients and healthy controls.
AB  - Although neuroendocrine changes after induction of hypoglycemia, in patients with
      diabetes and healthy persons, are thoroughly investigated, cognitive adaptation
      processes are still insufficiently understood. Changes in cognitive functions are
      mainly investigated by psychometric tests, which represent a summation of
      different cognitive processes. We aimed at dissecting cognitive adaptation into
      single components, i.e. stimulus selection, response choice, and reaction speed
      during a hyperinsulinemic hypoglycemic clamp in patients with type-1 diabetes and
      matched healthy controls. Using novel neurophysiological analyses, the event
      related potentials of early stimulus selection (selection negativity) and
      response selection (lateralized readiness potential) were studied, in addition to
      reaction time (RT). A total of 12 diabetic patients and 12 normal volunteers were
      studied while receiving a hyperinsulinemic hypoglycemic clamp. RTs and the event
      related potentials related to stimulus selection and response selection were
      significantly delayed during hypoglycemia in both groups, whereas early evoked
      potentials (P100) were unaltered. This suggests that hypoglycemia delays stimulus
      selection, with the consequence that also central and motor processing are
      delayed. In addition, patients with diabetes showed an earlier negative shift
      over the frontal cortex, which, when compared with the controls, reveals better
      adaptation to hypoglycemia in frontal cortical brain regions. After restoration
      of euglycemia stimulus selection, response selection and RT returned to baseline
      level in the type-1 group. In the control group, however, response selection and
      RTs were still delayed. This suggests that type-1 patients, possibly because of
      the past occurrence of hypoglycemic events, might be able to better cope with the
      hypoglycemic state than healthy volunteers who lack such a history. In summary,
      our data demonstrate, for the first time, that cognitive adaptation processes to
      an experimental hypoglycemic episode can clearly be dissected into their single
      components.

PMID- 10946879
TI  - Effect of long-term treatment with metformin added to hypocaloric diet on body
      composition, fat distribution, and androgen and insulin levels in abdominally
      obese women with and without the polycystic ovary syndrome.
AB  - Abdominal obesity and hyperinsulinemia play a key role in the development of the
      polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the
      administration of insulin-lowering drugs, such as metformin, are usually followed
      by improved hyperandrogenism and related clinical abnormalities. This study was
      carried out to evaluate the effects of combined hypocaloric diet and metformin on
      body weight, fat distribution, the glucose-insulin system, and hormones in a
      group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the
      abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group
      of 20 obese women who were comparable for age and pattern of body fat
      distribution but without PCOS. At baseline, we measured sex hormone, sex hormone
      binding globulin (SHBG), and leptin blood concentrations and performed an oral
      glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to
      measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women
      were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month,
      after which anthropometric parameters and CT scan were newly measured. While
      continuing dietary treatment, PCOS women and obese controls were subsequently
      placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8,
      respectively) or placebo (8 and 12, respectively), according to a double-blind
      design, for the following 6 months. Blood tests and the CT scan were performed in
      each woman at the end of the study while they were still on treatment. During the
      treatment period, 3 women of the control group (all treated with placebo) were
      excluded because of noncompliance; and 2 PCOS women, both treated with metformin,
      were also excluded because they became pregnant. Therefore, the women cohort
      available for final statistical analysis included 18 PCOS (10 treated with
      metformin and 8 with placebo) and 17 control women (8 treated with metformin and
      9 with placebo). The treatment was well tolerated. In the PCOS group, metformin
      therapy improved hirsutism and menstrual cycles significantly more than placebo.
      Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric
      dieting for 1 month similarly reduced BMI values and the waist circumference in
      both PCOS and control groups, without any significant effect on CT scan
      parameters. In both PCOS and control women, however, metformin treatment reduced
      body weight and BMI significantly more than placebo. Changes in the waist-to-hip
      ratio values were similar in PCOS women and controls, regardless of
      pharmacological treatment. Metformin treatment significantly decreased SAT values
      in both PCOS and control groups, although only in the latter group were SAT
      changes significantly greater than those observed during the placebo treatment.
      On the contrary, visceral adipose tissue area values significantly decreased
      during metformin treatment in both PCOS and control groups, but only in the
      former was the effect of metformin treatment significantly higher than that of
      placebo. Fasting insulin significantly decreased in both PCOS women and controls,
      regardless of treatment, whereas glucose-stimulated insulin significantly
      decreased only in PCOS women and controls treated with metformin. Neither
      metformin or placebo significantly modified the levels of LH, FSH,
      dehydroepiandrosterone sulphate, and progesterone in any group, whereas
      testosterone concentrations decreased only in PCOS women treated with metformin.
      SHBG concentrations remained unchanged in all PCOS women; whereas in the control
      group, they significantly increased after both metformin and placebo. Leptin
      levels decreased only during metformin treatment in both PCOS and control groups.
      (ABSTRACT TRUNCATED)

PMID- 10946880
TI  - An elevation of serum immunoglobulin E provides a new aspect of hyperthyroid
      Graves' disease.
AB  - In hyperthyroid Graves' disease, short-term methimazole is sufficient to induce
      lasting remission in some patients, but even long-term treatment fails to do so
      in others. We have evaluated the role of autoimmune abnormalities in the helper T
      cell type 2 (TH2)-interleukin-13 (IL-13)-TSH receptor system in maintaining
      hyperthyroidism by comparing IgE levels in patients with various thyroid
      diseases. One hundred and ninety-three patients with hyperthyroid Graves' disease
      were treated with methimazole, and blood samples were obtained to measure serum
      levels of T4, T3, TSH, thyroglobulin, antimicrosomal antibody, TSH binding
      inhibitory Ig (TBII), thyroid-stimulating antibody, thyroid stimulation-blocking
      antibody, IgE, interferon-gamma, IL-4, and IL-13. Elevation of serum IgE (> or =
      170 U/mL) was found in 35.5% of patients with hyperthyroid Graves' disease, and
      serum levels of T4, T:1, antimicrosomal antibody, and TBII were significantly
      greater in patients with IgE elevation than in those with normal serum IgE.
      During methimazole treatment, there was a parallel decrease in the serum T4
      concentration in the presence or absence of an IgE elevation. However, there was
      a significantly smaller decrease in TBII in patients with elevated IgE than in
      those with normal IgE. As a result, the remission rate was significantly greater
      in patients with normal IgE than in those with IgE elevation. Serum levels of IL
      13 were elevated in 64.7% of patients with IgE elevation in the absence of
      detectable TH1 marker, interferon-gamma. These findings suggest that in one third
      of patients with hyperthyroid Graves' disease, TH2 cells are stimulated and
      secrete excess amounts of IL-13, which subsequently stimulates B cells to
      synthesize more TSH receptor antibody and IgE, so that during methimazole
      treatment TBII decreases less in patients with IgE elevation, producing a lower
      remission rate.

PMID- 10946881
TI  - Combined pituitary hormone deficiency caused by a novel mutation of a highly
      conserved residue (F88S) in the homeodomain of PROP-1.
AB  - Mutations in the pituitary-specific paired-like homeodomain transcription factor,
      PROP-1, result in combined pituitary hormone deficiency. We studied a Brazilian
      girl, offspring of first cousins, who presented with short stature and
      deficiencies of GH, TSH, PRL, LH, and FSH. Her cortisol response to hypoglycemia
      was determined at age 4.9, 10.7, and 14.1 yr and remained normal. Magnetic
      resonance imaging at the age of 9 yr revealed an anterior pituitary lobe of
      diminished height (3 mm; normal, 4.5 +/- 0.6), but radiography revealed a sella
      turcica volume above the normal mean. Direct sequencing of the PROP-1 gene
      revealed homozygosity for a novel 263T>C transition that results in the
      replacement of a highly conserved phenylalanine by serine at codon 88 (F88S). F88
      constitutes the hydrophobic core of the first helix of the homeodomain of PROP-1,
      and the substitution by the polar residue serine is expected to alter the
      secondary structure and impair binding of the mutated PROP-1 to DNA target
      sequences. The F88S mutation (which corresponds to murine F85S) was introduced
      into the murine Prop-1 complementary DNA and its consequences on DNA binding and
      trans-activation were assessed in vitro. In contrast to wild-type Prop-1, the
      F88S mutant showed no significant DNA binding to a PRDQ9 Prop-1 response element
      in gel shift assays. Transcriptional activation of a luciferase reporter gene
      containing a PRDQ9 site upstream of a simian virus 40 promoter was reduced to
      approximately 34% compared with that of wild-type Prop-1 in transiently
      transfected TSA-201 human embryonic kidney cells. The F88S mutation further
      expands the repertoire of mutations in PROP-1.

PMID- 10946882
TI  - Familial dysalbuminemic hyperthyroxinemia in a Swiss family caused by a mutant
      albumin (R218P) shows an apparent discrepancy between serum concentration and
      affinity for thyroxine.
AB  - Familial dysalbuminemic hyperthyroxinemia (FDH), is the most common cause of
      inherited increase in serum total T4 (TT4) in the Caucasian population. It is
      caused by a mutation (R218H) in the human serum albumin (HSA) gene, resulting in
      10-fold higher affinity for T4 and, in heterozygous affected subjects, a TT4
      level 2-fold higher than that in subjects expressing the wild-type HSA only. We
      now report FDH in a Swiss family, caused by HSA R218P, previously reported in
      subjects of Japanese origin. In this form of FDH, serum TT4 levels are 14- to 20
      fold the normal mean, confirmed by measurements in serum extracts. TrT3 and TT3,
      concentrations are 7- and 2-fold above the mean, respectively. Thus, to maintain
      a normal free T4 level, the calculated affinity constant (Ka) of HSA R218P should
      be about 16-fold higher than that of HSA R218H. Surprisingly, the Ka values
      measured at saturation were similar: 5.4 x 10(6) and 6.4 x 10(6) mol/L(-1) for
      HSA R218H, respectively. To determine how subjects with HSA R218P and R218P
      maintain a euthyroid state despite the markedly high serum TT4, the concentration
      of dialyzable T4 was measured at increasing amounts of TT4. At a TT4 level
      equivalent to that found in the subjects with HSA R218P, the absolute FT4
      concentrations were 40, 432, and 1970 pmol/L for sera expressing HSAs R218P,
      R218H, and wild type, respectively. Thus, the affinity of HSA R218P for T4 must
      be higher than that of R218H to produce an 11-fold difference in FT4 at the same
      concentration ofTT4 This difference was obliterated at saturating concentrations
      of TT4 used for the determination of Ka values by the method of Scatchard.

PMID- 10946883
TI  - Decrease in carotid intima-media thickness after 1-year therapy with etidronate
      for osteopenia associated with type 2 diabetes.
AB  - It has been suggested that bisphosphonates may have some antiatherogenic actions
      in experimental animals or in vitro, but their effects on the atherogenic process
      in humans has not been reported. In the present study the effect of etidronate
      treatment on carotid arterial intima-media thickness was prospectively examined
      in 57 subjects with type 2 diabetes associated with osteopenia. After 1 yr of
      therapy with cyclical etidronate (200 mg/day for 2 weeks every 3 months), intima
      media thickness showed a decrease (mean +/- SE, 0.038 +/- 0.011 mm), which was
      significantly different from a change in 57 control subjects (0.023 +/- 0.015 mm;
      P < 0.005). Cardiovascular parameters were not changed after etidronate
      treatment. These findings suggest that etidronate in clinical dosage may have an
      antiatherogenic action, at least in type 2 diabetes, although its mechanisms
      remain to be elucidated.

PMID- 10946884
TI  - Dietary isoflavones affect sex hormone-binding globulin levels in postmenopausal
      women.
AB  - The studies presented in this report were designed to further investigate the
      causal association between phytoestrogen action and increase in sex hormone
      binding globulin (SHBG) levels. Phytoestrogens include isoflavones that bind to
      estrogen receptors and therefore exert estrogenic action. This study included 20
      postmenopausal women that ingested 30 g soy milk daily for 10 weeks. Plasma
      concentrations of isoflavones and SHBG were measured. Total isoflavones
      significantly increased from 0.014 +/- 0.01 micromol/L (baseline) to 0.53 +/-
      0.19 ,micromol/L, and paired responses showed that some subjects clearly
      increased their SHBG levels. The percent change in SHBG showed a positive
      correlation with phytoestrogen concentration; all women who had circulating
      phytoestrogen levels above 0.6 micromol/L increased by at least 30% their SHBG
      values. Results suggest that phytoestrogens may significantly increase SHBG in
      subjects whose SHBG concentrations are in the low end of the concentration range.

PMID- 10946885
TI  - The T 54 allele of the intestinal fatty acid-binding protein 2 is associated with
      a parental history of stroke.
AB  - To test the hypothesis that the A/T polymorphism of the fatty acid-binding
      protein 2 gene (FABP2) is associated with impaired lipid metabolism and
      cardiovascular disease, we compared clinical characteristics and a parental
      history of cardiovascular disease between 213 sibling pairs discordant for the
      polymorphism. Siblings with an excess of the T54 allele had higher triglyceride
      (P = 0.002) and cholesterol (P = 0.019) concentrations than siblings with the A54
      allele. Parents of offspring with the T54T and T54A genotypes reported an
      increased prevalence of stroke compared to parents of offspring with the A54A
      genotype (P = 0.007). In summary, we have confirmed the association of the FABP2
      T54 allele with increased concentrations of cholesterol and triglycerides in
      genotype-discordant sibling pairs. We also present novel evidence that genetic
      variation in the FABP2 gene may increase susceptibility to stroke.

PMID- 10946886
TI  - Effects of recombinant human insulin-like growth factor I administration on
      spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in
      anorexia nervosa.
AB  - Exaggerated GH and reduced insulin-like growth factor I (IGF-I) levels are common
      features in anorexia nervosa (AN). A reduction of the negative IGF-I feedback
      could account, in part, for GH hypersecretion. To ascertain this, we studied the
      effects of recombinant human (rh)IGF-I on spontaneous and GH-releasing hormone
      (GHRH)-stimulated GH secretion in nine women with AN [body mass index, 14.1 +/-
      0.6 kg/m2] and in weight matched controls (normal weight). Mean basal GH
      concentrations (mGHc) and GHRH (2.0 microg/kg, iv) stimulation were significantly
      higher in AN. rhIGF-I administration (20 microg/kg, sc) significantly reduced
      mGHc in AN (P < 0.01), but not normal weight, and inhibited peak GH response to
      GHRH in both groups; mGHc and peak GH, however, persisted at a significantly
      higher level in AN. Insulin, glucose, and IGFBP-1 basal levels were similar in
      both groups. rhIGF-I inhibited insulin in AN, whereas glucose remained unaffected
      in both groups. IGFBP-1 increased in both groups (P < 0.05), with significantly
      higher levels in AN. IGFBP-3 was under basal conditions at a lower level in AN (P
      < 0.05) and remained unaffected by rhIGF-I. This study demonstrates that a low
      rhIGF-I dose inhibits, but does not normalize, spontaneous and GHRH-stimulated GH
      secretion in AN, pointing also to the existence of a defective hypothalamic
      control of GH release. Moreover, the increased IGFBP-1 levels might curtail the
      negative IGF-I feedback in AN.

PMID- 10946887
TI  - Significance of mutations in the androgen receptor gene in males with idiopathic
      infertility.
AB  - Abnormal human spermatogenesis is caused by a variety of genetic and acquired
      conditions. Because spermatogenesis is dependent on androgens, some males may
      have a minimal form of androgen insensitivity that does not inhibit virilization
      but impairs fertility. This has lead us to investigate the possibility of
      abnormalities in the androgen receptor (AR) gene in a large cohort of males
      suffering from infertility of unknown cause. We studied 180 males with variable
      impairment of spermatogenesis. In all patients, serum levels of testosterone and
      gonadotropins were analyzed to define an androgen sensitivity index (ASI). Single
      strand conformation analysis and direct DNA sequencing of PCR-amplified blood
      leukocyte DNA were used to identify mutations within the whole coding region of
      the AR-gene. Endocrine and molecular investigations were compared with 53 normal
      males with proven fertility. In three infertile males, mutations in the AR were
      identified. Two unrelated males had the same variation within the first exon
      encoding for the transactivation domain of the receptor (Pro390Ser), whereas, in
      the third, a mutation in the hormone-binding region was characterized
      (Gln798Glu). All identified mutation carriers had a significantly elevated ASI. A
      proportion of males with idiopathic infertility carry relevant variations within
      the AR-gene. These males may be distinguished on the basis of hormone levels,
      calculating the ASI, although this index lacks specificity.

PMID- 10946888
TI  - Growth hormone treatment of short children born small for gestational age: growth
      responses with continuous and discontinuous regimens over 6 years.
AB  - We report an epi-analysis of 6-yr growth responses obtained with GH treatment in
      short children born small for gestational age (SGA). Four randomized, multicenter
      studies explored the effects of continuous and discontinuous regimens of GH
      treatment in short, non-GH-deficient SGA children. A total of 49 untreated and
      139 treated children were followed over 2 and 6 yr, respectively. At the start of
      the study, the age of these 188 children averaged 5.2 yr (range, 2-8 yr), height
      was -3.4 SD score, and height adjusted for parental height was -2.4 SD score.
      Onset of puberty was observed in 46% of the GH-treated cohort, on the average, at
      10.7 yr in girls and 11.7 yr in boys. Two studies essentially investigated the
      effects of continuous GH treatment at a dose of 33 or 67 microg/kg, day, and two
      studies focused on the growth characteristics during an initial GH treatment for
      2-3 yr (dose range, 33-100 microg/kg x day), followed by a withdrawal phase of 1
      2 yr, and then by either no or 1 or more episodes of further GH treatment (33 or
      67 microg/kg x day). Continuous GH treatment for 6 yr resulted in height
      increments of 2.0 +/- 0.2 SD (33 microg/kg x day; n = 35) and 2.7 +/- 0.2 SD (67
      microg/kg x day; n = 27). Discontinuous GH treatment was given to 77 children,
      most of them experiencing only 1 (n = 47) or 2 (n = 26) treatment phases with an
      average duration of 2.0 yr. All these children received GH during the first 2 yr;
      the dose was only 32 microg/kg x day when averaged over 6 yr. Some
      individualization of treatment schedules was allowed, and the majority of
      investigators seemed to aim for a low normal height level, adjusted for parental
      height. After 2 yr, the mean adjusted height SD score had increased to -0.4 +/-
      0.1 and stabilized thereafter. Bone maturation progressed similarly in all
      treatment subgroups, and after 6 yr of study, bone age remained slightly delayed
      compared to chronological age. Multivariate analysis identified the average GH
      dose over 6 yr, parental-adjusted height SD score, and age at start as prime
      predictors of the growth response. GH treatment was well tolerated. In
      conclusion, this epi-analysis of growth responses over 6 yr confirms the
      administration of GH as an effective approach to normalize the stature of short,
      non-GH-deficient SGA children, at least during childhood and early puberty. In
      addition, it is now increasingly apparent that a relatively broad spectrum of GH
      regimens is effective, and this experience should facilitate the design of more
      individualized treatment schedules in the future, in particular for young
      children.

PMID- 10946889
TI  - Deficiency of total and nonglycosylated amylin in plasma characterizes subjects
      with impaired glucose tolerance and type 2 diabetes.
AB  - This study was undertaken to characterize first and second phase secretory
      profiles of total and nonglycosylated amylin and insulin and to determine whether
      excessive glycosylation of amylin or hyperamylinemia is a feature of abnormal
      glucose tolerance in humans. Plasma concentrations of total and nonglycosylated
      amylin and serum immunoreactive insulin were measured under identical
      hyperglycemic conditions using the hyperglycemic clamp technique in subjects with
      type 2 diabetes, impaired and normal glucose tolerance. Both amylin and insulin
      concentrations followed a biphasic pattern in subjects with normal and impaired
      glucose tolerance. In the subjects with normal and impaired glucose tolerance,
      the second phase amylin concentrations markedly exceeded those of the first
      phase, whereas the reverse was true for insulin. The first phase concentrations
      of both peptides were significantly lower in impaired than the normal glucose
      tolerance subjects. In patients with type 2 diabetes no first phase peak for
      either amylin or insulin could be identified, and the second phases of both
      amylin and insulin were significantly lower compared to subjects with normal or
      impaired glucose tolerance. Nonglycosylated amylin concentrations accounted for
      25-45% of total amylin, regardless of glucose tolerance, and mimicked the pattern
      of total amylin concentrations. In summary: 1) glucose-induced increases in the
      magnitude of the first and second phase amylin plasma concentrations differed
      from those of insulin; 2) subjects with impaired glucose tolerance and more
      strikingly those with type 2 diabetes have impaired amylin responses; and 3) the
      ratio of nonglycosylated to total amylin is normal irrespective of glucose
      tolerance. These data imply, in view of many reports describing accumulation of
      amyloid in the pancreas, that circulating levels of amylin decrease as amyloid
      deposits accumulate and beta-cell function deteriorates and that the amount of
      glycosylated amylin in plasma is not increased in patients with type 2 diabetes.

PMID- 10946890
TI  - Exercise-induced increase in circulating adrenomedullin is related to mean blood
      pressure in heart transplant recipients.
AB  - Adrenomedullin (ADM) is a newly discovered potent vasorelaxing and natriuretic
      peptide that recently has been shown to be increased after heart transplantation.
      To investigate the hemodynamic factors modulating its release and the eventual
      role of ADM in blood pressure regulation after heart transplantation, seven
      matched heart-transplant recipients (Htx) and seven normal subjects performed a
      maximal bicycle exercise test while monitoring for heart rate, blood pressure,
      and circulating ADM. Baseline heart rate and systemic blood pressure were higher
      in Htx; left ventricular mass index and ADM tended to be higher after heart
      transplantation and correlated positively in Htx (r = 0.79, P = 0.03). As
      expected, exercise-induced increase in heart rate was lower in Htx than in
      controls (60 +/- 11 % vs. 121 +/- 14 %, respectively) and blood pressure increase
      was similar in both groups. Maximal exercise increased significantly plasma ADM
      in both groups (from 25.3 +/- 3.1 to 30.7 +/- 3.5 pmol/L, P < 0.05 and from 15.2
      +/- 1.4 to 29.1 +/- 4.4 pmol/L, P = 0.02 in Htx and controls, respectively), the
      hypotensive peptide level remaining elevated until the 30th min of recovery. A
      significant inverse relationship was observed between peak mean blood pressure
      and circulating ADM in Htx (r = -0.86, P < 0.02). Besides showing that
      circulating ADM is increased after heart transplantation, the present study
      demonstrates a positive relationship between baseline ADM and left ventricular
      mass index. Furthermore, maximal exercise-induced increase in ADM is inversely
      related to mean blood pressure in Htx, suggesting that ADM might participate in
      blood pressure regulation during exercise after heart transplantation.

PMID- 10946891
TI  - A prospective longitudinal study of serum testosterone, dehydroepiandrosterone
      sulfate, and sex hormone-binding globulin levels through the menopause
      transition.
AB  - The aims of this study were to describe, in relation to date of final menses, the
      average androgen levels of women in the years before and after this date, and to
      determine the extent to which these average levels were dependent on age and body
      mass index (BMI) and the degree of tracking in residual androgen levels, or the
      extent to which individuals above (below) the mean for their age or time relative
      to final menstrual period (FMP) and BMI remain above (below) the mean as time
      progresses. Serial levels of serum sex hormone-binding globulin (SHBG),
      testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured
      annually in 172 women from the Melbourne Women's Midlife Health Project who
      experienced a natural menopause during 7 yr of follow-up. Fasting blood samples
      were drawn between days 4-8 if women were still menstruating or after 3 months of
      amenorrhea. The free androgen index (FAI) was calculated as the ratio ofT to SHBG
      x 100. Means of the log-transformed androgen levels were analyzed as a double
      logistic function of time relative to FMP as well as age and BMI, and
      correlations between repeated androgen levels were measured. Mean SHBG levels
      decreased by 43% from 4 yr before to 2 yr after the FMP. The time of most change
      was 2 yr before FMP [95% confidence interval (CI), 0.8-3.2]. SHBG levels were, on
      the average, 5% lower for each halving of estradiol (E2) levels and 4% lower for
      each kilogram per m2 of BMI (P < 0.0001). About one third of the decline in SHBG
      was explained by E2 and BMI. After adjusting for all variables, SHBG showed
      strong tracking. Mean T levels did not vary with time relative to FMP and were
      independent of age and BMI. Residual values of T showed weak tracking. The FAI
      increased by 80% from 4 yr before FMP to 2 yr after FMP, and changed maximally
      2.2 yr before FMP (95% CI, 1.2-3.2). The FAI was not related to age or E2, but
      was, on the average, 4% higher for each kilogram per m2 of BMI (P < 0.0001).
      Residual values of FAI showed moderate tracking. Mean DHEAS levels were not
      related to the FMP, but were 1.5% lower for each year of age (P < 0.01) and 3.8%
      lower for each kilogram per m2 of BMI (P < 0.0001). Residual values of DHEAS
      showed strong tracking. It is concluded that SHBG and FAI levels change at the
      time of the menopause, at least partially due to the decline in E2. DHEAS
      decreases as a function of age, not time relative to FMP, and T remains unchanged
      during the menopausal years. SHBG and DHEAS show a high degree of stability
      within an individual over time.

PMID- 10946892
TI  - Transdermal testosterone gel improves sexual function, mood, muscle strength, and
      body composition parameters in hypogonadal men.
AB  - Testosterone (T) therapy for hypogonadal men should correct the clinical
      abnormalities of T deficiency, including improvement of sexual function, increase
      in muscle mass and strength, and decrease in fat mass, with minimal adverse
      effects. We have shown that administration of a new transdermal T gel formulation
      to hypogonadal men provided dose proportional increases in serum T levels to the
      normal adult male range. We now report the effects of 180 days of treatment with
      this 1% T gel preparation (50 or 100 mg/day, contained in 5 or 10 g gel,
      respectively) compared to those of a permeation-enhanced T patch (5 mg/day) on
      defined efficacy parameters in 227 hypogonadal men. In the T gel groups, the T
      dose was adjusted up or down to 75 mg/day (contained in 7.5 g gel) on day 90 if
      serum T concentrations were below or above the normal male range. No dose
      adjustment was made with the T patch group. Sexual function and mood changes were
      monitored by questionnaire, body composition was determined by dual energy x-ray
      absorptiometry, and muscle strength was measured by the one repetitive maximum
      technique on bench and leg press exercises. Sexual function and mood improved
      maximally on day 30 of treatment, without differences across groups, and showed
      no further improvement with continuation of treatment. Mean muscle strength in
      the leg press exercise increased by 11 to 13 kg in all treatment groups by 90
      days and did not improve further at 180 days of treatment. Moderate increases
      were also observed in arm/chest muscle strength. At 90 days of treatment, lean
      body mass increased more in the 100 mg/day T gel group (2.74 +/- 0.28 kg; P =
      0.0002) than in the 50 mg/day T gel (1.28 +/- 0.32 kg) and T patch groups (1.20
      +/- 0.26 kg). Fat mass and percent fat were not significantly decreased in the T
      patch group, but showed decreases in the T gel groups (50 mg/day, -0.90 +/- 0.32
      kg; 100 mg/day, - 1.05 +/- 0.22 kg). The increase in lean mass and the decrease
      in fat mass were correlated with the changes in average serum T levels attained
      after transdermal T replacement. These beneficial effects of T replacement were
      accompanied by the anticipated increases in hematocrit and hemoglobin but without
      significant changes in the lipid profile. The increase in mean serum prostate
      specific antigen levels (within the normal range) was correlated with serum
      levels of T. The greatest increases were noted in the 100 mg/day T gel group.
      Skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of
      subjects in the permeation-enhanced T patch group. We conclude that T gel
      replacement improved sexual function and mood, increased lean mass and muscle
      strength (principally in the legs), and decreased fat mass in hypogonadal men
      with less skin irritation and discontinuation compared with the recommended dose
      of the permeation-enhanced T patch.

PMID- 10946893
TI  - Prevalence of primary aldosteronism among Asian hypertensive patients in
      Singapore.
AB  - Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA
      as the screening test for primary aldosteronism in hypertensive populations
      suggested that the prevalence may be as high as 5-15%, with well over half of the
      subjects having normal serum potassium concentrations. Despite an increasing
      clinical awareness of this entity, many clinicians are reluctant to consider
      routine screening for primary aldosteronism in essential hypertensive patients
      because there are few community-based prevalence studies of primary aldosteronism
      in different populations. Furthermore, genetic and environmental differences may
      affect the prevalence and presentation of primary aldosteronism in distinct
      populations. This study was designed to determine the prevalence of primary
      aldosteronism in the predominantly Chinese population in Singapore. Three hundred
      and fifty unselected adult hypertensive patients attending two primary care
      clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA
      (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were
      obtained simultaneously. Subjects with renal insufficiency (serum creatinine,
      >140 micromol/L) and those treated with glucocorticoids or spironolactone were
      excluded. Screening was considered positive if the PAC: PRA ratio was more than
      20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was
      confirmed with the determination of PAC after 2 L saline administered iv over 4
      h. Adrenal computed tomographic (CT) scans were performed in biochemically
      confirmed cases of primary aldosteronism. Further localization with adrenal vein
      sampling was carried out in selected patients with equivocal findings on adrenal
      CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135
      men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only
      13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L).
      Confirmatory studies were carried out in 56 (89%) of the subjects with a positive
      PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as
      the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary
      aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary
      aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling
      indicated that half of the patients with primary aldosteronism may have had
      potentially curable unilateral adrenal adenoma. Our data suggest that primary
      aldosteronism occurs in at least 5% of the adult Asian hypertensive population,
      and approximately half of these individuals may have potentially curable,
      unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the
      poor predictive value of hypokalemia in both the diagnosis and the exclusion of
      primary aldosteronism.

PMID- 10946894
TI  - Impact of time interval from the last meal on glucose response to exercise in
      subjects with type 2 diabetes.
AB  - We evaluate the influence of the time interval from the last meal on the blood
      glucose response to exercise in men with type 2 diabetes. Nineteen men with type
      2 diabetes participated in an exercise training program carried out at 60% of
      maximal oxygen uptake (VO2peak) for 1 h, 3 times a week. Capillary whole blood
      glucose was measured immediately before and after each exercise session, and the
      time interval from the last meal (breakfast, lunch, or dinner) was recorded.
      Seven time intervals were considered (fasted overnight and 0-1, 1-2, 2-3, 3-4, 4
      5, and 5-8 h postmeal). A total of 1,045 exercise sessions were analyzed. There
      was no change in blood glucose levels when individuals were in the fasted state
      (mean +/- SE, 8.1 +/- 0.2 vs. 8.1 +/- 0.1 mmol/L; before vs. after,
      respectively). However, blood glucose decreased by 28 +/- 1% at 0-1 h, by 33 +/-
      1% at 1-2 h, by 35 +/- 1% at 2-3 h, by 38 +/- 2% at 3-4 h, by 43 +/- 2% at 4-5 h,
      and by 23 +/- 3% at 5-8 h (all P < 0.001). These results demonstrate that 1 h of
      ergocycle exercise has no clinical impact on blood glucose when performed in the
      fasted state in men with type 2 diabetes, whereas a significant decrease in blood
      glucose should be expected when the same exercise is performed postprandially.

PMID- 10946895
TI  - Distribution and abundance of messenger ribonucleic acid for growth hormone
      receptor isoforms in human tissues.
AB  - Two alternatively spliced exon 9 variants of human GH receptor (GHR) messenger
      ribonucleic acid (mRNA), GHR-(1-279) and GHR(1-277), were recently identified in
      liver. They encode receptor proteins lacking most of the intracellular domain and
      inhibit GH action in a dominant negative manner. Little is known about tissue
      distribution and abundance of these GHR isoforms. We have developed quantitative
      RT-PCR assays specific for the full-length and truncated GHRs and investigated
      their expression in various human tissues and cell lines. The mRNA of full-length
      GHR and GHR-(1-279) were readily detectable in all tissues investigated, with
      liver, fat, muscle, and kidney showing high levels of expression. These two
      receptor isoforms were also detected in a range of human cell lines, with
      strongest expression in IM9, a lymphoblastoid cell line. In contrast, GHR-(1277)
      message was expressed at low levels in liver, fat, muscle, kidney, and prostate
      and in trace amount in IM9 cells. Full-length GHR was the most abundant isoform,
      accounting for over 90% of total receptor transcripts in liver, fat, and muscle
      for quantitative RT-PCR. However, liver had 2- to 4-fold more full-length
      receptor mRNA and 16- to 40-fold more GHR-(1-277) mRNA than fat and muscle,
      whereas the mRNA levels of GHR-(1-279) were similar in the three tissues. GHR-(1
      279) constituted less than 4% in liver and 7-10% in fat and muscle. GHR-(1-277)
      accounted for 0.5% of total GHR transcripts in liver and less than 0.1% in the
      other two tissues. These data suggest that the absolute and relative abundance of
      mRNA of the three GHR isoforms may be tissue specific. The regulation of
      expression of exon 9 alternatively spliced GHR variants may provide a potential
      mechanism for modulation of GH sensitivity at the tissue level.

PMID- 10946896
TI  - Induction of specific phosphodiesterase isoforms by constitutive activation of
      the cAMP pathway in autonomous thyroid adenomas.
AB  - Thyrocytes largely depend on cAMP signaling for replication and differentiation.
      This pathway may be constitutively activated by mutations of the TSH receptor
      (TSHR) and Gsalpha in autonomous thyroid adenomas (ATAs). Because steady state
      cAMP results from production by adenylyl cyclase and degradation by
      phosphodiesterases (PDEs), we evaluated PDE activity and expression in ATAs with
      wild-type and mutant TSHR and Gsalpha. Activating mutations of TSHR and Gsalpha
      were identified in 7 and 1 of 18 ATAs, respectively. No difference was observed
      in the cAMP content in ATAs with or without activating mutants. In the
      surrounding normal thyroid tissue (NTs), PDE activity was 80%
      isobutylmethylxanthine sensitive, with the major contribution by PDE1 and a minor
      contribution by PDE4. No differences were observed in PDE activities between NTs
      and ATAs with wild-type TSHR and Gsalpha. In contrast, in the presence of mutant
      TSHRs or Gsalpha, total PDE activity was higher. This increase was primarily due
      to PDE4 induction (917 +/- 116% over NTs), associated with a minor PDE1 increase
      only in ATAs with mutant TSHR. By RT-PCR, increments of PDE4D and 4C messenger
      ribonucleic acids were found in the ATAs with mutant TSHR or Gsalpha, whereas
      messenger ribonucleic acids encoding other cAMP-specific PDEs were not
      significantly increased. This study provides a characterization of the PDEs
      expressed in human thyroid and demonstrates a dramatic PDE4 induction in the ATAs
      bearing mutant TSHR or Gsalpha genes. The increase in cAMP-degrading activity may
      represent a marker of constitutive adenylyl cyclase activation and constitutes an
      intracellular feedback mechanism with significant impact on the phenotypic
      expression of the activating mutations.

PMID- 10946897
TI  - Characterization of the uridine diphosphate-glucuronosyltransferase-catalyzing
      thyroid hormone glucuronidation in man.
AB  - Increased thyroid hormone glucuronidation in rats caused by exposure to
      xenobiotics has stimulated a search for the individual uridine diphosphate
      glucuronosyltransferases (UGTs) catalyzing this reaction in rats and man.
      Microsomal preparations from Crigler-Najjar liver, normal human liver, and kidney
      have been used to try to identify the UGT isoforms responsible for
      glucuronidation of the thyroid hormones. The predominant thyroid hormone released
      from the thyroid gland, T4, and the inactive rT3 are glucuronidated by cloned
      expressed bilirubin UGT1A1 and also phenol UGT1A9. Results from Crigler-Najjar
      microsomal samples indicate that UGT1A1 is the main contributor to thyroid
      hormone glucuronidation in the liver, with rT3 being the preferential substrate.
      In kidney microsomes thyroid hormone glucuronidation is more complex, suggesting
      that more than just the UGT1A9 isoform may be involved. Bioactive T3 is not
      significantly glucuronidated by these isoforms and other UGTs, and
      sulfotransferases may be involved.

PMID- 10946898
TI  - In vivo and in vitro degradation of glucagon-like peptide-2 in humans.
AB  - Glucagon-like peptide-2 (GLP-2), an intestinal product of glucagon gene
      expression which induces intestinal growth in mice, has been proposed as a
      treatment for intestinal insufficiency. GLP-2 is metabolized extensively by
      dipeptidyl peptidase IV (DPP-IV) in rats, but less is known about its fate in
      humans. Therefore, GLP-2 metabolism was investigated in healthy volunteers after
      1) a 500-Cal mixed meal (n = 6), 2) iv infusion of synthetic human GLP-2 (0.8
      pmol/kg x min; n = 8), 3) a sc bolus injection (400 microg; n = 9), and 4) in
      vitro incubation in plasma and blood (1,000 pmol/L; n = 4). GLP-2 concentrations
      were determined by N-terminal RIA measuring only intact GLP-2, side-viewing RIA
      measuring intact and degraded forms [e.g. GLP-2-(3-33) arising from DPP-IV
      degradation], and high performance liquid chromatography (HPLC). Meal ingestion
      elevated plasma GLP-2 (intact, 16 +/- 3 to 73 +/- 10 pmol/L at 90 min), and HPLC
      revealed two immunoreactive components: intact GLP-2 (57 +/- 2%) and GLP-2-(3
      33). GLP-2 infusion increased plasma levels [intact, 9 +/- 4 to 131 +/- 11
      pmol/L; total, 23 +/- 7 to 350 +/- 18 pmol/L; the differences represent GLP-2-(3
      33)]. The elimination t(1/2) values were 7.2 +/- 2 min (intact GLP-2) and 27.4 +/
      5.4 min [GLP-2-(3-33)], and MCRs were 6.8 +/- 0.6 and 1.9 +/- 0.3 mL/kg x min,
      respectively. Subcutaneous injection increased intact GLP-2 to maximally 1,493 +/
      250 pmol/L at 45 min, whereas total GLP-2 increased to 2,793 +/- 477 pmol/L at
      90 min. At 60 min, plasma contained 69 +/- 1% intact GLP-2. In vitro the t(1/2)
      values were 8.0 +/- 1.5 h (plasma) and 3.3 +/- 0.3 h (blood). GLP-2-(3-33) was
      the only degradation product identified by HPLC, and a DPP-IV inhibitor abolished
      the degradation of GLP-2 in vitro. We conclude that GLP-2 is extensively degraded
      to GLP-2-(3-33) in humans, presumably by DPP-IV. Nevertheless, 69% remains intact
      1 h after GLP-2 injection, supporting the possibility of sc use in patients with
      intestinal insufficiency.

PMID- 10946899
TI  - All-trans-retinoic acid modulates expression levels of thyroglobulin and
      cytokines in a new human poorly differentiated papillary thyroid carcinoma cell
      line, KTC-1.
AB  - A new human thyroid carcinoma cell line, KTC-1, was established from the
      malignant pleural effusion of a recurrent thyroid carcinoma patient. Cytogenetic
      analysis revealed a normal karyotype, and no p53 mutation in exons 5-9 was
      detected. This cell line is tumorigenic in athymic nude mice. Histological
      findings by light and electron microscopy, such as the absence of follicular
      structures and the existence of intranuclear cytoplasmic inclusions and psammoma
      bodies, indicated transplanted tumors to be a poorly differentiated papillary
      thyroid carcinoma. A low expression level of thyroglobulin was detected by
      immunocytochemistry and RT-PCR. Messenger ribonucleic acid (mRNA) expression of
      thyroid transcription factor-1 and PAX-8 was also detected. No mRNA expression of
      TSH receptors, thyroid peroxidase, or Na+/I- symporter was detected. Interleukin
      6 and leukemia inhibitory factor were secreted into the medium. These findings
      suggest this cell line to be functionally poorly differentiated. Moreover, all
      trans-retinoic acid increased the mRNA expression of thyroglobulin and decreased
      both the mRNA expression and secretion of interleukin-6 and leukemia inhibitory
      factor while significantly stimulating growth. RT-PCR analysis of retinoic acid
      receptors (RARs) revealed that KTC-1 cells express a moderate level of RARalpha
      and -gamma, but a low level of RARbeta. This cell line may be useful for studying
      redifferentiation therapy for thyroid carcinoma.

PMID- 10946900
TI  - Progesterone receptor isoform A but not B is expressed in endometriosis.
AB  - We previously demonstrated that 17beta hydroxysteroid dehydrogenase type 2, the
      enzyme that inactivates estradiol to estrone, is expressed in luteal eutopic
      endometrium in response to progesterone but not in simultaneously biopsied
      peritoneal endometriotic tissue. This molecular evidence of progesterone
      resistance, together with the clinical observation of resistance of endometriosis
      to treatment with progestins, led us to determine the levels of progesterone
      receptor (PR) isoforms PR-A and PR-B in eutopic endometrial and extra-ovarian
      endometriotic tissues. It was proposed that progesterone action on target genes
      is mediated primarily by homodimers of PR-B, whereas the truncated variant PR-A
      acts as a repressor of PR-B function. Immunoprecipitation, followed by Western
      blot analysis, was performed to detect bands specific for PR-A and PR-B in paired
      samples of endometriotic and eutopic endometrial tissues simultaneously biopsed
      from 18 women undergoing laparoscopy during various phases of the menstrual
      cycle. PR-B was present in 17 of 18 eutopic endometrial samples, and its level
      increased in the preovulatory phase, as expected, whereas PR-A was detected in
      all samples (n = 18) with a similar, but less prominent, cyclic variation in its
      levels. In endometriotic samples, however, no detectable PR-B could be
      demonstrated, whereas PR-A was detected in all samples (n = 18), albeit in much
      lower levels and without any cyclic variation in contrast with the eutopic
      endometrium. Levels of PR-A and PR-B in endometriotic and eutopic endometrial
      tissues were determined and compared after normalization to total protein and
      estrogen receptor-alpha levels. Using RNase protection assay, we also
      demonstrated indirectly that only PR-A transcripts were present in endometriotic
      tissue samples (n = 8), whereas both PR-A and PR-B transcripts were readily
      detectable in all eutopic endometrial samples (n = 8). This was indicative that
      failure to detect PR-B protein in endometriotic tissues is due to the absence of
      PR-B transcripts. We conclude that progesterone resistance in endometriotic
      tissue from laboratory and clinical observations may be accounted for by the
      presence of the inhibitory PR isoform PR-A and the absence of the stimulatory
      isoform PR-B.

PMID- 10946901
TI  - Corticotropin-independent Cushing's syndrome caused by an ectopic adrenal
      adenoma.
AB  - Although nonsecreting suprarenal embryonic remnants are frequently found in the
      urogenital tract, adenomatous transformation resulting in glucocorticoid excess
      is a rare phenomenon. We report a case of a 63-yr-old woman that presented with
      new-onset hirsutism, facial plethora, hypertension, centripetal obesity, and a
      proximal myopathy. The 24-h urinary free cortisol excretion rate was elevated,
      and the serum ACTH level was suppressed. The patient failed an overnight and low
      dose dexamethasone suppression test and did not respond to CRH stimulation. In
      light of the undetectable baseline morning ACTH levels and the blunt response to
      CRH, the diagnosis of corticotropin-independent Cushing's syndrome was made.
      Imaging studies revealed normal adrenal glands and enlargement of a left
      pararenal nodule incidentally observed 4 yr before the onset of symptoms.
      Dramatic resolution of symptoms was observed after surgical removal of the 3.5-cm
      mass. Pathological exam confirmed adrenocortical adenoma in ectopic adrenal
      tissue. The case reported here represents the unusual circumstance in which the
      development of adenomatous transformation of ectopic adrenal tissue has been
      prospectively observed with imaging studies. It illustrates the importance of
      considering ectopic corticosteroid-secreting tumors in the context of
      corticotropin-independent Cushing's syndrome.

PMID- 10946902
TI  - Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip.
AB  - An increase in osteoblast and osteocyte apoptosis has been demonstrated in mice
      and humans receiving glucocorticoids and may be involved in the pathogenesis of
      the associated osteonecrosis. To examine the spatial relationship between
      osteocyte apoptosis and glucocorticoid-induced osteonecrosis, we determined the
      prevalence of osteocyte apoptosis in whole femoral heads obtained from patients
      who underwent prosthetic hip replacement because of osteonecrosis due to chronic
      glucocorticoid treatment (n = 5), alcoholism (n = 3), and trauma (n = 1) as well
      as in femoral neck cores from patients with sickle cell disease (n = 5). Abundant
      apoptotic osteocytes and cells lining cancellous bone were found juxtaposed to
      the subchondral fracture crescent in femurs from the patients with glucocorticoid
      excess. In contrast, apoptotic bone cells were absent from the specimens taken
      from patients with trauma or sickle cell disease and were rare with alcohol
      abuse. These results indicate that glucocorticoid-induced osteonecrosis is a
      misnomer. The bone is not necrotic; instead, it shows prominent apoptosis of
      cancellous lining cells and osteocytes. Glucocorticoid-induced osteocyte
      apoptosis, a cumulative and irreparable defect, could uniquely disrupt the
      mechanosensory function of the osteocyte network and thus start the inexorable
      sequence of events leading to collapse of the femoral head.

PMID- 10946903
TI  - Effects of sex steroid deprivation/administration on hair growth and skin sebum
      production in transsexual males and females.
AB  - To investigate androgen effects on the skin pilosebaceous unit, we studied 21
      male-to-female transsexuals and 17 female-to-male transsexuals receiving cross
      sex hormones. At baseline and after 4, 8, and 12 months, hair growth was
      evaluated by the Ferriman-Gallwey score; acne by the Leeds classification; hair
      growth rate, density, and shaft diameter by image analysis; and sebum production
      by Sebutape. In males, estrogens and antiandrogens reduced plasma testosterone to
      below 1.0 nmol/L. Though all parameters of hair growth and sebum production
      declined, facial hair growth continued. After 4 months, the decrease in shaft
      diameter had reached its maximum and seemed inversely associated with changes in
      hair growth length and density. In females, testosterone increased hair growth
      rate and sebum production. After 12 months, hairs on the cheek and abdomen had
      not yet reached diameters found in males. 5alpha-Androstane-3alpha,17beta-diol
      glucuronide levels were only weakly associated with hair growth and sebum
      production. In conclusion, administration of estrogens and antiandrogens affects
      length and diameter of hairs at different rates. In the virtual absence of
      androgens, hair growth continues but at a slower rate. In women, after 12 months
      of androgen administration, hair diameters have not reached values of adult men.

PMID- 10946904
TI  - Novel mutations of the autoimmune regulator gene in two siblings with autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is the
      first multiple autoimmune disease that has been shown to be caused by mutations
      of a single gene named autoimmune regulator (AIRE). Fourteen different mutations
      of the AIRE gene have been identified in 61 patients from 55 families with
      APECED. However, there has been no report documenting AIRE gene mutations in the
      Asian population. We report on 2 siblings with variable manifestations of APECED
      who were born to a Japanese mother and a Korean father. The 11yr-old girl had
      intractable thrush and ungual candidiasis, hypoparathyroidism, and occipital
      alopecia. The 9-yr-old boy had mild ungual candidiasis alone. Direct sequencing
      revealed novel frameshift mutations of the AIRE gene: an insertion of a cytosine
      at nucleotide 29635 at the exon 10 (29635insC), which should lead to a premature
      termination at the codon 371, producing a truncated protein missing the second
      plant homeodomain-type zinc finger motif and the third LXXLL motif, and a
      deletion of a guanine at nucleotide 33031 at the exon 13 (33031delG), which
      should result in a premature termination at the codon 520, yielding a truncated
      protein missing the third LXXLL motif. The mother was heterozygous for 29635insC,
      and the father was heterozygous for 33031delG. The frameshift mutations were
      undetected in 40 alleles of 20 Japanese control subjects. The results imply that
      the C-terminus of AIRE protein including the third LXXLL motif plays a critical
      role in the development of APECED, and that the phenotypic spectrum can vary
      between siblings with the same mutations.

PMID- 10946905
TI  - Short stature homeobox-containing gene duplication on the der(X) chromosome in a
      female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature.
AB  - We report on a Japanese female with 45,X[40]/46,X, der(X)[60], primary
      amenorrhea, and tall stature. She was confirmed to have complete gonadal
      dysgenesis at 19 yr of age and was placed on hormone replacement therapy. Growth
      assessment revealed that she had a low normal height until her early teens, but
      continued to grow with a nearly constant height velocity in her late teens,
      attaining a final height of 172 cm (+ 2.9 SD), which surpassed her target height
      range. Fluorescence in situ hybridization analysis for 10 loci/regions on the X
      chromosome together with the whole X-chromosome and the Xp-specific and Xq
      specific paintings showed that the der(X) chromosome was associated with
      duplication of roughly distal half of Xp, including SHOX (short stature homeobox
      containing gene), and deletion of most of Xq. Microsatellite analysis for eight
      loci at Xp22 and nine loci at Xq26-28 indicated that the normal X-chromosome was
      of maternal origin, and the der(X) chromosome was of paternal origin. The
      results, in conjunction with the adult height data in 47,XXX, 46,XX gonadal
      dysgenesis, 47,XXY, 46,XY gonadal dysgenesis, and 46,X, idic(Xq-), suggest that
      the tall stature of this female is caused by the combined effects of SHOX
      duplication on the der(X) chromosome and gonadal estrogen deficiency.
      Furthermore, the similarity in the growth pattern between this female and
      patients with estrogen resistance or aromatase deficiency implies that the
      association of an extra copy of SHOX with gonadal estrogen deficiency may
      represent the further clinical entity for tall stature resulting from continued
      growth in late teens or into adulthood.

PMID- 10946906
TI  - Role of matrix metalloproteinase 9 in pituitary tumor behavior.
AB  - The matrix metalloproteinases (MMPs) are a family of zinc-containing
      endopeptidases that are able to degrade the extracellular matrix and allow
      angiogenesis and tumor invasion. The vast majority of pituitary tumors are benign
      and do not metastasize to distant sites, although they may invade locally. The
      aim of this study was to determine whether expression of the collagenase MMP-9
      may play a role in allowing angiogenesis and invasion by different pituitary
      tumor types. Tumor expression of MMP-9 was investigated using a monoclonal
      antibody on a series of well-characterized paraffin-embedded sections of
      pituitary tumors. Invasive macroprolactinomas (n = 11) were significantly more
      likely to express MMP-9 than noninvasive macroprolactinomas (n = 8) (P = 0.003).
      Invasive macroprolactinomas showed higher-density MMP-9 staining than noninvasive
      tumors (P < 0.05). MMP-9 expression did not differ between noninvasive tumors and
      normal pituitary gland, or between different sized prolactinomas. MMP-9
      expression was related to aggressive tumor behavior. It was higher in invasive
      macroprolactinomas (P = 0.003) when compared with noninvasive macroprolactinomas
      or the normal anterior pituitary gland. In addition, although there was no
      difference in whether MMP-9 was present or not when nonfunctioning adenomas that
      recurred were compared with those that did not, samples of recurrent tumor at the
      second presentation were more likely to express MMP-9 (P = 0.01). Pituitary
      carcinomas were significantly more likely to be MMP-9 positive compared with
      normal anterior pituitary gland (P = 0.05), but there was no difference from
      invasive adenomas. Angiogenesis assessed by vascular density was related to MMP-9
      expression (P < 0.05). In summary, we have shown the presence of MMP-9 expression
      in some invasive and recurrent pituitary adenomas, and in the majority of
      pituitary carcinoma. The mechanisms whereby MMP-9 expression influences tumor
      recurrence and invasiveness, and its association with angiogenesis, remains to be
      elucidated. However, these observations suggest that a future potential
      therapeutic strategy for some pituitary tumors may be administration of a
      synthetic MMP-9 inhibitor.

PMID- 10946907
TI  - Hormonal regulation of radioiodide uptake activity and Na+/I- symporter
      expression in mammary glands.
AB  - The observation that radioiodide uptake (RAIU) activity, mediated by the Na+/I-
      symporter (NIS), is significantly increased in lactating breast suggests that
      RAIU and NIS expression in mammary gland are modulated by hormones involved in
      active lactation. We showed that both the NIS expression level and RAIU in rat
      mammary gland are maximal during active lactation compared to those in the
      mammary glands of virgin and pregnant rats as well as the involuting mammary
      gland. In the lactating mammary gland, NIS is clustered on the basolateral
      membrane of alveolar cells as a lesser glycosylated form than NIS in thyroid. The
      RAIU of lactating mammary gland was partially inhibited by treatment with a
      selective oxytocin antagonist or bromocriptine, an inhibitor of PRL release.
      These findings suggest that RAIU and NIS expression in mammary gland are at least
      in part modulated by oxytocin and PRL. Indeed, we showed that NIS messenger
      ribonucleic acid level was increased in a dose-dependent manner by oxytocin and
      PRL in histocultured human breast tumors.

PMID- 10946908
TI  - Pteridin-dependent hydroxylases as autoantigens in autoimmune polyendocrine
      syndrome type I.
AB  - Autoimmune polyendocrine syndrome type I (APS I) is characterized by
      autoantibodies, often directed towards tissue-specific enzymes in the affected
      organs. We have earlier reported the identification of tryptophan hydroxylase
      (TPH) and tyrosine hydroxylase (TH) as autoantigens in APS I associated with
      intestinal dysfunction and alopecia, respectively. These two enzymes, together
      with phenylalanine hydroxylase (PAH), constitute the group of biopterin-dependent
      hydroxylases, which all are involved in the biosynthesis of neurotransmitters. A
      clone encoding PAH was used for in vitro transcription/translation, followed by
      immunoprecipitation with sera from 94 APS I patients and 70 healthy controls. Of
      the APS I patients, 25% had PAH antibodies, and no reactivity was detected in the
      controls. No association with the main clinical components of APS I was found
      with PAH antibodies. Altogether, 59 sera from the 94 APS I patients reacted with
      at least one of TPH, TH, or PAH, whereas 35 showed no reactivity. Nineteen of the
      sera contained antibodies towards all enzymes, 12 to TPH only and 12 to TH only.
      No sera showed antibodies that reacted to only PAH. An immunocompetition assay
      demonstrated that the reactivity against PAH represents a cross-reactivity with
      TPH, whereas antibodies against TPH and TH are directed towards epitopes unique
      for the two enzymes.

PMID- 10946909
TI  - Variability of the insulin receptor substrate-1, hepatocyte nuclear factor-1alpha
      (HNF-1alpha), HNF-4alpha, and HNF-6 genes and size at birth in a population-based
      sample of young Danish subjects.
AB  - Reduced size at birth has been proposed to be a risk factor for insulin
      resistance and type 2 diabetes. It is, however, not known whether this
      association is explained by unfavorable intrauterine environment or by specific
      susceptibility genotypes predisposing for both reduced fetal growth and insulin
      resistance and type 2 diabetes. The present study was performed to evaluate
      whether previously identified amino acid polymorphisms of genes that from animal
      models have been suggested to play important roles during fetal development are
      associated with alterations in size at birth. The study population comprised 380
      subjects randomly recruited from a population of young Danish Caucasian
      individuals, aged 18-32 yr. The original data of birth length and weight for 331
      of 380 subjects were obtained from the midwife records. The Gly/Arg972 of insulin
      receptor substrate-1 (IRS-1), the Thr/Ile130 of the hepatocyte nuclear factor
      4alpha (HNF-4alpha), the Pro/Ala75 of HNF-6, and the Ile/Leu27, Ala/Val93, and
      Ser/Asn4s7 polymorphisms of the HNF-lalpha gene were examined for association
      with birth weight and length and the ponderal index. Using a generalized linear
      model, including gender and the genotype as fixed variables, and applying
      Bonferroni correction for multiple testing, we could not demonstrate any
      significant differences in these estimates among wild-type, heterozygous, and
      homozygous carriers with respect to any of the gene variants. In conclusion,
      common variability in the genes encoding the IRS-1, HNF-lalpha, HNF-4alpha, and
      HNF-6 proteins can be excluded as major factors influencing size at birth among
      Danish Caucasian subjects.

PMID- 10946910
TI  - Detection of endocrine disrupting chemicals in samples of second trimester human
      amniotic fluid.
AB  - Man-made chemicals that have been shown to modulate endocrine function in animal
      models, so-called "endocrine disrupters", are suspected to play a role in the
      development of male reproductive tract abnormalities and neurobehaviroal deficits
      in children. However in utero exposure to environmental contaminants has not been
      documented previously. The present study was performed to test our hypothesis
      that man-made chemicals can be quantified in human amniotic fluid during the
      second trimester. Gas chromatographic/mass spectrometric (GC/MS) analysis was
      performed on amniotic fluid samples (n=53) from women (n=51) undergoing routine
      amniocentesis with a mean (+/- SEM) age of 36.5 +/- 0.5 years and between 15 and
      23 weeks of gestation. Analytes included common PCB congeners, the DDT
      metabolites p,p'-DDE, and o,p'-DDE as well as the pesticides: hexachlorobenzene
      (HCB); and the three isomers of hexachlorocyclohexane (alpha,beta and gamma-HCH).
      The limit of quantitation (LOQ) for PCBs was 0.01 ng/ml and for the other
      organochlorines contaminants is was 0.1 ng/ml. The contaminants alpha-HCH with a
      mean (+/- SD) concentration of 0.15 +/- 0.06 (ng/ml) and p,p'-DDE with a mean (+/
      SD) concentration of 0.21 +/- 0.18 ng/ml were detected in the amniotic fluid.
      PCB specific congeners were detected with a much lower frequency and levels were
      in the range of the LOQ. Overall one in three amniotic fluid samples tested
      positive for at least one environmental contaminant. Therefore, we conclude that
      approximately one in three fetuses in the Los Angeles area are exposed to
      endocrine modulatory environmental contaminants in utero the consequences of
      which remain unknown at this time.

PMID- 10946911
TI  - Growth hormone receptor antagonist therapy in acromegalic patients resistant to
      somatostatin analogs.
AB  - Transsphenoidal surgical resection is the primary therapy for acromegaly caused
      by GH secreting pituitary adenomas. Medical therapy for patients not controlled
      by surgery includes primarily somatostatin analogs and secondarily dopamine
      agonists, both of which inhibit pituitary growth hormone secretion. A novel GH
      receptor antagonist (pegvisomant) binds to hepatic GH receptors and inhibits
      peripheral insulin-like growth factor-1 generation. Six patients resistant to
      maximal doses of octreotide therapy received pegvisomant - three received placebo
      or pegvisomant 30 mg or 80 mg weekly for 6 weeks and three received placebo and
      pegvisomant 10-20 mg/d for 12 weeks. Thereafter, all patients received daily
      pegvisomant injections of doses determined by titrating IGF-1 levels. Serum total
      IGF-1 levels were normalized in all six acromegalic patients previously shown to
      be resistant to somatostatin analogs via a novel mechanism of peripheral GH
      receptor antagonism. The GH receptor antagonist is a useful treatment for
      patients harboring GH-secreting tumors who are resistant to octreotide.

PMID- 10946912
TI  - Independent confirmation of a major locus for obesity on chromosome 10.
AB  - Linkage results obtained in genome-wide scans for complex phenotypes require
      confirmation in independent samples. Recently, linkage of obesity to chromosome
      10p12 with a maximal multipoint LOD score of 4.85 was reported upon use of an
      affected sib-pair approach including nuclear families in which the adult index
      case had a BMI > or = 40 kg/m2 and at least one further sibling had a BMI > or =
      27 kg/m2 (Hager et al., 1998, Nat Genet 20:304-8). To attempt to replicate this
      linkage finding we genotyped 11 markers spanning approximately 23 cM from 10p13
      to 10ql1 in a total of 386 individuals stemming from 93 nuclear families with two
      or more young obese offspring with a BMI > or = 90th age percentile. The highest
      multipoint maximum likelihood binomial (MLB) LOD score using the extreme
      concordant sib-pair approach in which one sib had a BMI > or = 95th percentile,
      and other sibs a BMI > or = 90th percentile was 2.32. Six markers yielded nominal
      p-values < 0.05, the highest two point MLB-LOD score of 2.45 (nominal p = 0.0004)
      was obtained for the marker TCF8. Transmission disequilibrium tests for the most
      frequent parental allele yielded no nominal p-value < 0.05. The linkage results
      confirm the presence of a major susceptibility locus for obesity in a region near
      the centromere on chromosome 10.

PMID- 10946913
TI  - Raloxifene acutely stimulates nitric oxide release from human endothelial cells
      via an activation of endothelial nitric oxide synthase.
AB  - Raloxifene is a selective estrogen receptor modulator (SERM) clinically effective
      for the prevention of postmenopausal osteoporosis. Estrogen's effect on
      cardiovascular diseases is mainly dependent on direct actions on the vascular
      wall. Since raloxifene has an endothelium-dependent relaxing effect, we studied
      the effects of this molecule on nitric oxide (NO) release from cultured human
      umbilical vein endothelial cells. Clinically effective concentrations of the
      compound triggered a rapid and dose-dependent release of NO from endothelial
      cells. Raloxifene-induced NO production was dependent on an estrogen receptor
      mediated mechanism, since it was abolished by the pure estrogen receptor
      antagonist ICI 182,780. Treatment of endothelial monolayers with raloxifene was
      not associated with changes in endothelial nitric oxide synthase (eNOS) messenger
      RNA or protein, showing that raloxifene does not increase NO release through a
      transcriptional increase of eNOS. Indeed, raloxifene-induced NO production is due
      to an estrogen receptor-dependent acute stimulation of eNOS enzymatic activity.
      In conclusion, raloxifene activates eNOS in human endothelial cells, exerting a
      potentially important direct vasculo-protective effect stimulating endothelial NO
      production.

PMID- 10946914
TI  - Glucose challenge stimulates reactive oxygen species (ROS) generation by
      leucocytes.
AB  - Diabetes mellitus is associated with increased ROS generation, oxidative injury
      and obesity. To elucidate the relationship between nutrition and ROS generation,
      we have investigated the effect of glucose challenge on ROS generation by
      leucocytes, p47phox protein, a key protein in the enzyme NADPH oxidase and alpha
      tocopherol levels. Blood samples were drawn from 14 normal subjects prior to, at
      1, 2 and 3 h following ingestion of 75 g glucose. ROS generation by
      polymorphonuclear leucocytes (PMNL) and mononuclear cells (MNC) increased to a
      peak of 244 +/- 42% and 233 +/- 34% of the basal respectively at 2h. The levels
      of p47phox in MNC homogenates increased significantly at 2 h and 3 h after
      glucose intake. alpha-Tocopherol levels decreased significantly at 1 h, 2 h and 3
      h. We conclude that glucose intake stimulates ROS generation and p417phox of
      NADPH oxidase; increases oxidative load and causes a fall in alpha-tocopherol
      concentration.

PMID- 10946915
TI  - Involvement of nitric oxide in parasympathetic and antidromic vasodilatations in
      cat lower lip.
AB  - The involvement of nitric oxide (NO) in the lower lip vasodilatations mediated
      via parasympathetic and antidromic mechanisms was examined in alpha
      chloralose/urethane-anesthetized cats, with the two types of blood flow responses
      being recorded separately (by laser Doppler flowmeter) from the two sides of the
      lower lip. The central cut end of the lingual nerve (LN) or the peripheral cut
      end of the inferior alveolar nerve (IAN) was electrically stimulated to elicit
      parasympathetic or antidromic vasodilatation, respectively, in the lower lip.
      N(G)-nitro-L-arginine methyl ester (L-NAME), but not N(G)-nitro-D-arginine methyl
      ester (D-NAME) (each at 30 mg/kg), markedly reduced the increases in lip blood
      flow evoked by stimulation, the reduction being to a similar degree irrespective
      of whether LN or IAN was stimulated. Pretreatment with L-arginine did not prevent
      the L-NAME-induced attenuation of either type of vasodilatation. In conclusion,
      these results suggest that synthesized NO may have a common site of action in
      antidromic and parasympathetic vasodilator pathways to the cat lower lip.

PMID- 10946916
TI  - The time-course of the effects of contralateral sound on the level of distortion
      product otoacoustic emissions.
AB  - The effects of the addition of contralateral noise on the level of distortion
      product otoacoustic emissions (DPOAEs) were examined. In the present study, the
      DPOAEs were recorded for a relatively long period (2 minutes), and the time
      course of the effects of contralateral sound on the level of DPOAEs were
      considered. In general, the addition of the contralateral noise resulted in
      suppression of the level of DPOAEs. The time-course of this suppression appeared
      to depend on the level of the contralateral noise. When the level of the
      contralateral noise was low, the suppression of the level of DPOAEs seemed to be
      largely unchanged for at least 2 minutes. In contrast, when a relatively high
      level of contralateral noise was used, the suppression of the level of DPOAEs
      decreased with time.

PMID- 10946917
TI  - Anthropometric obesity indices in relation to age and gender in Japanese adults.
AB  - The body mass index (BMI), waist circumference, waist to hip ratio, waist to
      height ratio and skinfolds (near-umbilical and iliac areas) in three age groups
      (35-44, 45-54 and 55-64 years) were compared in 3117 men and 997 women in Tokyo.
      In both genders, height was significantly shorter, while the waist to hip ratio
      and waist to height ratio were significantly higher, in the older groups. In the
      men, there were no significant differences in BMI and waist circumference among
      the three age groups, but the iliac skinfold was significantly thinner in each
      older group, and the paraumbilical skinfold was thinner in the group aged 55-64
      years. In the women, the paraumbilical skinfold was significantly thicker in each
      older group, while waist circumference and the iliac skinfold were significantly
      larger or thicker in the group aged 55-64 years, and BMI was larger in the groups
      aged 45-54 and 55-64 years. There were age-related discrepancies between BMI and
      other obesity indices in the different genders, in that only the waist to height
      ratio and waist to hip ratio increased with age in both genders.

PMID- 10946918
TI  - Effect of carnosine on rats under experimental brain ischemia.
AB  - The effect of dietary carnosine on the behavioral and biochemical characteristics
      of rats under experimental ischemia was studied. Carnosine was shown to improve
      the animals orientation and learning in "Open Field" and "T-Maze" tests, and this
      effect was accompanied with an increase in glutamate binding to N-methyl-D
      aspartate (NMDA) receptors in brain synaptosomes. Long-term brain ischemia
      induced by both sides' occlusion of common carotid arteries resulted in 55%
      mortality of experimental rats, and those who survived were characterized by
      partial suppression of orientation in T-maze. In the group of rats treated with
      carnosine, mortality after ischemic attack was decreased (from 55% to 17%) and
      most of the learning parameters were kept at the pre-ischemic level. Monoamine
      oxidase B (MAO B) activity in brain of the carnosine treated rats was not changed
      by ischemia significantly (compared to that of ischemic untreated rats) but NMDA
      binding to brain synaptosomal membranes being increased by ischemic attack was
      significantly suppressed and reached the level characteristic of normal brain.
      The suggestion was made that carnosine possesses a dual effect on NMDA receptors
      resulting in increase in their amount after long-term treatment but decrease the
      capacity to bind NMDA after ischemic attack.

PMID- 10946919
TI  - Basic fibroblast growth factor caused no change in collateral flow or infarct
      size of acutely-infarcted myocardium in rats.
AB  - The extent to which local administration of basic fibroblast growth factor (bFGF)
      increased regional myocardial blood flow (Qm) to acutely-infarcted areas of the
      heart, thereby mediating myocardial salvage, was examined in this study.
      Myocardial infarction was induced in two groups of rats by ligation of the left
      coronary artery. The bFGF group (n = 16) received 100 microg bFGF in
      physiological saline by intramyocardial injection into the infarcted area, while
      the control group (n = 7) received only saline. The rats were then maintained for
      four weeks. Among the controls, Qm decreased in the infarcted areas to 6.5+/-6.7%
      of that in the noninfarcted areas immediately after coronary ligation, then
      increased to 11.5+/-8.6% during the four-week maintenance period. In the bFGF
      group, Qm immediately decreased to 17.5+/-14.7% following ligation and remained
      stable thereafter (18.3+/-9.1%). There were no significant differences between
      the bFGF and control groups with respect to Qm, the number of viable myocardial
      cells or the extent of myocardial fibrosis. In this study we failed to show any
      significant effect of bFGF on coronary angiogenesis in acutely-ischemic
      myocardium in rats. Application of bFGF using different dosage, different routes
      of administration, measuring new capillaries morphologically will be needed to
      confirm the present negative results.

PMID- 10946920
TI  - Infiltration of CD8+ T cells in non-small cell lung cancer is associated with
      dedifferentiation of cancer cells, but not with prognosis.
AB  - CD8+ T cells infiltrating within cancer cell nests in human colorectal cancer
      were associated with a favorable patients' survival, suggesting the presence of
      anti-tumor immunity. The present study was designed to examine this concept in
      non-small cell lung cancer (NSCLC) by a retrospective analysis of 128 surgically
      resected cases. Immunohistochemical analysis showed that the number of CD8+ T
      cells within cancer cell nests in NSCLC was related to the histological subtype
      (large cell carcinoma or squamous cell carcinoma > adenocarcinoma) and the degree
      of dedifferentiation (undifferentiated type > differentiated type). In contrast
      to colorectal cancer, the number of CD8+ T cells in NSCLC had no statistically
      significant impact on the patients' survival. The present study demonstrated that
      the degree of infiltration of CD8+ T cells within cancer cell nests is dependent
      on the dedifferentiation of cancer cells in NSCLC, which could be one of the
      important aspects for the study of tumor immunity.

PMID- 10946922
TI  - The tumbling concha-cartilage flap for correction of lop ear.
AB  - This article presents a new surgical method that uses tumbling concha-cartilage
      flaps to correct lop ears. Through a posterior or anterior auricular skin
      incision, a rectangular or T-shaped cartilage flap is elevated from the concha
      and tumbled backward. After passing under the postauricular skin, the flap's tip
      is fixed to the lidded helix or scapha. The recoiling force of the flap's conchal
      side enables the lidded portion to be in a normal, erect, anatomic position. The
      method also increases the vertical height of the ear and creates a normally
      shaped scapha. Sixteen lop ears were corrected using this procedure, with most of
      them maintaining natural auricular features. Therefore, this method was
      considered effective for the correction of moderate lop ear deformity.

PMID- 10946921
TI  - Quantification of osseous facial dysmorphology in untreated unilateral coronal
      synostosis.
AB  - Unilateral coronal synostosis results in dysmorphology of the midface in addition
      to well-characterized cranial and orbital deformities. Because most American
      infants with this problem have undergone cranio-orbital surgery within their
      first year of life for the past 25 years, a paucity of data exist regarding the
      natural history of untreated unilateral coronal synostosis. In an attempt to
      remedy this void, an international search was conducted to identify computed
      tomography data sets of living individuals with untreated unilateral coronal
      synostosis; data were obtained from two European centers and one center in the
      United States. Results limited to the study of the midface are presented here.
      Digital data from high-resolution head computed tomography scans of 11 living,
      white individuals with untreated unilateral coronal synostosis were obtained from
      three craniofacial centers (in Denmark, The Netherlands, and the United States).
      Image volumes were constructed from each scan using ANALYZE biomedical imaging
      software. Fourteen pairs of three-dimensional distances were calculated on the
      ipsilateral (the side of the synostosis) and the contralateral (the side opposite
      to the synostosis) hemifaces using 11 osseous landmarks. The resulting
      measurements were expressed as a ratio of the ipsilateral: contralateral sides.
      Descriptive statistics were derived for the untreated unilateral coronal
      synostosis population and compared with analogous measurements performed on dried
      skulls. Age at computed tomography ranged from 1.1 to 21.1 years (mean, 6.6
      years; median, 4.1 years). Twelve of the 14 measured distances differed by
      greater than 5 percent on the ipsilateral side, and all but one of these
      measurements were decreased on the ipsilateral side when compared with
      contralateral values. The results of this study support the following
      conclusions: (1) There are discrete and measurable differences in the facial
      morphology between patients with untreated unilateral coronal synostosis and
      normal skulls. (2) Intercenter and international collaboration can provide a
      sufficient number of individuals with rare craniofacial anomalies to
      quantitatively determine group characteristics. (3) Quantitative documentation of
      rare anomaly natural history is necessary for quantitative outcome assessment of
      treated patients.

PMID- 10946923
TI  - Nasal fracture management: minimizing secondary nasal deformities.
AB  - Current management techniques for acute nasal fractures result in a high
      incidence of posttraumatic nasal deformity (14 to 50 percent). Associated
      traumatic edema, preexisting nasal deformity, and occult septal injury account
      for most of these acute reduction failures. Working with a detailed patient
      history and a physical examination that included rigid nasal endoscopy, the
      authors formulated a clinical algorithm for acute nasal fracture management, the
      use of which can reduce the incidence of posttraumatic nasal deformity. In this
      article, the authors review the literature, then discuss their management
      techniques over the past 11 years in 110 cases with a 9 percent nasal revision
      rate. This low incidence of revision is attributed to complete nasal assessment
      (bony and septum), use of outpatient controlled general anesthesia, and primary
      septal reconstruction in cases with severe septal fracture dislocation.

PMID- 10946924
TI  - Treatment of hypoglossia-hypodactyly syndrome without extremeity anomalies.
AB  - Three cases of hypoglossia-hypodactyly syndrome without limb deformities are
      reported. All exhibited different degrees of tongue hypoplasia, micrognathia,
      retrognathia with a very narrow space between the left and right halves of the
      mandible, constricted isthmus, and only one lower incisor. Bone lengthening for
      the midline mandibular hypoplasia and orthodontic treatment were performed in the
      three cases with satisfactory results.

PMID- 10946926
TI  - Evaluation and comparison of aesthetic results and patient satisfaction with
      bilateral breast reduction using the inferior pedicle and McKissock's vertical
      bipedicle dermal flap techniques.
AB  - In the last two decades, McKissock's technique for reduction mammaplasty was
      largely replaced by Robbins's inferior pedicle technique. However, a substantial
      number of plastic surgeons still perform McKissock's technique in the belief that
      it is superior to the inferior pedicle technique in terms of aesthetic results
      and complication rate. In this study, the authors compared the aesthetic results,
      complication rates, and patient satisfaction with the two techniques. Numerous
      studies in the past few years have shown an improvement in physical symptoms in
      addition to excellent patient satisfaction after breast reduction. However,
      almost all of these studies have used questionnaires that were mailed to the
      patients for evaluation. In the present study, aesthetic evaluations by the
      surgeon and an objective observer were performed in addition to evaluations by
      the patients themselves, thereby increasing the objectivity and the significance
      of the patients' evaluations. Two groups of 24 and 27 patients were compared. The
      groups were almost identical in terms of demographic data and the amount of
      breast tissue removed. The aesthetic results were good to excellent in both
      groups, and the groups had similar complication rates. When the patients'
      evaluations were compared with those of the surgeon and the objective observer,
      no significant difference was found between the observer and the patients. In one
      of the groups, the surgeon's evaluations were significantly higher than those of
      the patients, although they were not significantly higher than the observer's. In
      terms of aesthetic results, complication rates, and patient satisfaction, no
      differences existed between the groups. In addition, the patients' evaluations
      were determined to be a reliable index of aesthetic results and, in these cases,
      they were often identical to objective evaluations.

PMID- 10946925
TI  - Measuring health state preferences in women with breast hypertrophy.
AB  - The purpose of this article is to introduce the measurement of utilities, or
      patient preferences, to the plastic surgery community. Specifically, the study
      demonstrated the development and validation of a utility measure for estimating
      the health-related quality of life in women with breast hypertrophy. Two self
      administered instruments were developed, a Wheel and a Table. All subjects
      completed the utility assessments for their "current health" and again for
      "breast-related symptoms." The reliability of the instruments was assessed in
      repeat (test-retest) interviews of 47 women within 10 to 18 days. Utilities
      obtained with the new instruments were also compared with the performance of
      other validated utility assessment instruments, including a visual analogue
      scale, a computer-based instrument (U-Titer), and a preference classification
      system (EuroQol). Of the 47 women in the test-retest reliability study, 21 had
      experienced breast hypertrophy (13 had not had reduction surgery and 8 had
      undergone reduction mammaplasty). Mean utility values for breast-related symptoms
      among women with breast hypertrophy (n = 13) were: Table, 0.85; Wheel, 0.90; and
      U-Titer, 0.66. Current health utility scores were significantly lower for women
      with breast hypertrophy (n = 13), as measured by all instruments except the
      Wheel. The Table had good reliability and distinguished women with breast
      hypertrophy from those without. Although the Table provided higher utility values
      for the same health state compared with the computer-based interview (U-Titer),
      it is much less costly to implement. The Table is recommended as a reasonable
      alternative for use in multicenter studies of women with breast hypertrophy. The
      reported utility value for breast hypertrophy of 0.86 is much lower than
      predicted. It is comparable with the reported burden of living with other health
      conditions, such as moderate angina (0.90) and a kidney transplant (0.84).

PMID- 10946927
TI  - Geographic variation in postmastectomy breast reconstruction rates.
AB  - Data on postmastectomy breast reconstructive surgery were examined for 52,357
      female breast cancers that were treated with mastectomy and diagnosed in
      geographic areas covered by the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program. The proportion of cancers that involved
      reconstruction varied in these geographic areas in each age group (under age 70
      years) by a factor of about four or five, even after adjustment for stage at
      diagnosis, marital status, and poverty rate of county of residence at diagnosis.
      Studies are needed to explain the large differences in reconstruction rates by
      geographic area.

PMID- 10946928
TI  - Sensitivity of breasts reconstructed with the autologous latissimus dorsi flap.
AB  - The purpose of this study was to measure, both objectively and subjectively, the
      sensitivity of breasts reconstructed with the autologous latissimus dorsi flap
      and to compare these results with those of other reconstruction techniques,
      especially the transverse rectus abdominis myocutaneous flap. The study
      population included 50 patients with autologous latissimus dorsi flap breast
      reconstruction; these patients had an average age of 51 years and an average
      follow-up of 27 months. Patients answered a seven-item questionnaire that
      attempted to define the sensitivity of the reconstructed and opposite breasts.
      This sensitivity was then measured objectively using standard techniques for
      heat, cold, and tactile sensations. After statistical analysis, these results
      were compared with those published for other reconstruction techniques. Overall
      results were comparable or superior to those published for other techniques for
      autologous breast reconstruction. A total of 56 percent of patients had fine or
      very fine sensitivity, but 70 percent deemed this sensitivity to be less than
      that of the opposite breast. A total of 94 percent of patients perceived the
      reconstructed breast as integral to their body image. The superior medial part of
      the breast had the greatest sensitivity, both objectively and subjectively.
      Autologous latissimus dorsi breast reconstruction, a good technique with
      excellent aesthetic results, affords satisfactory sensitivity. This is yet
      another advantage of the technique.

PMID- 10946929
TI  - Postoperative adjuvant irradiation: effects on tranverse rectus abdominis muscle
      flap breast reconstruction.
AB  - The use of postoperative irradiation following oncologic breast surgery is
      dictated by tumor pathology, margins, and lymph node involvement. Although
      irradiation negatively influences implant reconstruction, it is less clear what
      effect it has on autogenous tissue. This study evaluated the effect of
      postoperative irradiation on transverse rectus abdominis muscle (TRAM) flap
      breast reconstruction. A retrospective review was performed on all patients
      undergoing immediate TRAM flap breast reconstruction followed by postoperative
      irradiation between 1988 and 1998. Forty-one patients with a median age of 48
      years received an average of 50.99 Gy of fractionated irradiation within 6 months
      after breast reconstruction. All except two received adjuvant chemotherapy. Data
      were obtained from personal communication, physical examination, chart, and
      photographic review. The minimum follow-up time was 1 year, with an average of 3
      years, after completion of radiation therapy. Nine patients received pedicled
      TRAM flaps and 32 received reconstruction with microvascular transfer. Fourteen
      patients had bilateral reconstruction, but irradiation was administered
      unilaterally to the breast with the higher risk of local recurrence. The
      remaining 27 patients had unilateral reconstruction. All patients were examined
      at least 1 year after radiotherapy. No flap loss occurred, but 10 patients (24
      percent) required an additional flap to correct flap contracture. Nine patients
      (22 percent) maintained a normal breast volume. Hyperpigmentation occurred in 37
      percent of the patients, and 56 percent were noted to have a firm reconstruction.
      Palpable fat necrosis was noted in 34 percent of the flaps and loss of symmetry
      in 78 percent. Because the numbers were small, there was no statistical
      difference between the pedicled and free TRAM group. However, as a group, the
      findings were statistically significant when compared with 1,443 nonirradiated
      TRAM patients. Despite the success of flap transfer, unpredictable volume,
      contour, and symmetry loss make it difficult to achieve consistent results using
      immediate TRAM breast reconstruction with postoperative irradiation. TRAM flap
      reconstruction in this setting should be approached cautiously, and delayed
      reconstruction in selected patients should be considered. Patients should be
      aware that multiple revisions and, possibly, additional flaps are necessary to
      correct the progressive deformity from radiation therapy.

PMID- 10946930
TI  - Clinical applications of the posterior rectus sheath-peritoneal free flap.
AB  - Soft-tissue injuries involving the dorsum of the hand and foot continue to pose
      complex reconstructive challenges in terms of function and contour. Requirements
      for coverage include thin, vascularized tissue that supports skin grafts and at
      the same time provides a gliding surface for tendon excursion. This article
      reports the authors' clinical experience with the free posterior rectus sheath
      peritoneal flap foil dorsal coverage in three patients. Two patients required
      dorsal hand coverage; one following acute trauma and another for delayed
      reconstruction 1 year after near hand replantation. A third patient required
      dorsal foot coverage for exposed tendons resulting from skin loss secondary to
      vasculitis. In all three patients, the flap was harvested through a paramedian
      incision at the lateral border of the anterior rectus sheath. After opening the
      anterior rectus sheath, the rectus muscle was elevated off of the posterior
      rectus sheath and peritoneum. When elevating the muscle, the attachments of the
      inferior epigastric vessels to the posterior rectus sheath and peritoneum were
      preserved while ligating any branches of these vessels to the muscle. Segmental
      intercostal innervation to the muscle was preserved. The deep inferior epigastric
      vessels were then dissected to their origin to maximize pedicle length and
      diameter. The maximum dimension of the flaps harvested for the selected cases was
      16 X 8 cm. The anterior rectus sheath was closed primarily with non-absorbable
      suture. Mean follow-up was 1 year, and all flaps survived with excellent contour
      and good function in all three patients. Complications included a postoperative
      ileus in one patient, which resolved after 5 days with nasogastric tube
      decompression.

PMID- 10946931
TI  - The management of cubital tunnel syndrome: a meta-analysis of clinical studies.
AB  - Despite extensive clinical experience in treating cubital tunnel syndrome,
      optimal surgical management remains controversial. A meta-analysis of 30 studies
      with accurate preoperative and postoperative staging was undertaken. Patients
      were staged preoperatively into minimum, moderate, and severe groups on the basis
      of clinical presentation. Treatment modalities included nonoperative management,
      surgical decompression, medial epicondylectomy, anterior subcutaneous
      transposition, and anterior submuscular transposition. Statistical analysis using
      a standard SAS database with analysis of variance and chi-square tests was used
      to assess the efficacy of each therapeutic modality. For minimum-staged patients,
      all modalities produced similar degrees of satisfaction. However, total relief
      occurred most after medial epicondylectomy and least after anterior subcutaneous
      transposition. Patients treated nonoperatively had the highest rate of
      recurrence. For moderate-staged patients, submuscular transposition was most
      efficacious, whereas patients with nonoperative management fared the worst.
      Finally, for severe-staged patients, current therapeutic modalities were not
      consistently effective, with medial epicondylectomy producing the poorest
      operative result. This article reveals statistically significant differences in
      outcomes among therapeutic modalities, which may assist in treatment planning; it
      introduces standardized methods to aid in determining, analyzing, and
      communicating treatment outcomes.

PMID- 10946932
TI  - Sixty-four cases of thumb and finger reconstruction using transplantation of the
      big toe skin-nail flap combined with the second toe or the second and third toes.
AB  - The purpose of this article is to introduce the results of thumb and finger
      reconstruction using transplantation of the big toe wraparound flap combined with
      the second toe or the second and third toes. Between August of 1981 and December
      of 1998, in a series of 64 cases involving 58 patients with digitless hands,
      either (1) the thumb and index fingers were reconstructed by transplantation of a
      big toe wraparound flap combined with the adjacent second toe harvested from the
      ipsilateral foot; or (2) the thumb, index, and long fingers were reconstructed by
      transplantation of an ipsilateral big toe wraparound flap combined with the
      adjacent second and third toes. The phalanx of the new thumb was usually an iliac
      block. The success rate of this series was 92.2 percent. At long-term follow-up,
      the average static 2-point discrimination was less than 10 mm. The distance
      between the tip of the new thumb and the new index finger ranged from 6 to 10 cm
      (average, 8 cm). Opposition action was nimble and forceful. The patients could
      lift a 6- to 12-kg weight with their reconstructed digits. All patients were
      satisfied with their new hands and were able to use them in their daily
      activities. The transplants for reconstructing the thumb and fingers are
      harvested from the same foot in a procedure known as one-foot donation. Function
      of the bilateral digitless hand can be recovered with this procedure.

PMID- 10946933
TI  - Tensor fasciae latae perforator flap for reconstruction of composite Achilles
      tendon defects with skin and vascularized fascia.
AB  - The surgical management of large defects of the Achilles tendon and overlying
      skin is very demanding and necessitates, as a rule, a free vascularized graft.
      The ideal characteristics of a thin layer of skin and a strong tendon component,
      combined with a reliable blood supply and minimal morbidity at the donor site,
      have only been partially met by all previous grafts used in this situation. The
      authors performed reconstructions in five patients with large defects of the
      Achilles tendon and overlying skin by using a perforator flap derived from the
      tensor fasciae latae flap. A vascularized skin-subcutis-fascia lata flap could be
      raised by dissecting out two to three perforating arteries through the tensor
      fasciae latae muscle to the ascending branch of the lateral circumflex femoral
      artery; the muscle was left in situ in the process. All the flaps took well
      without complications. At final examination after an average of 20 months, the
      reconstructed Achilles tendon showed good functional results, although there was
      a 50 to 70 percent reduction in power during plantar flexion when compared with
      the normal side. A very good aesthetic result could be obtained after a debulking
      operation was performed on the skin flap.

PMID- 10946934
TI  - Secondary corrections of the vulva in male-to-female transsexuals.
AB  - From December of 1980 to May of 1998, 390 male-to-female transsexuals underwent
      vaginoplasty by inversion of the penile skin and a triangular perineoscrotal
      flap. Although minor modifications were made throughout the years, the basic
      surgical technique remained the same over this 17.5-year period. In 86 of the 390
      patients (22 percent), secondary corrections of the vulva were deemed necessary.
      A total of 130 corrections were performed in these 86 patients. In the same 17.5
      year period, the authors performed 26 secondary corrective procedures in 19
      patients in whom the initial vaginoplasty had been done elsewhere. Bilateral Z
      plasties were performed 69 times to center the labia in instances when the
      ventral part of the labia majora remained too far apart. This is not advisable,
      primarily because it will reduce the vascular supply of the penile skin flap.
      Introital widening by five-flap advancement was performed in 40 cases in which a
      dorsal skin fold obstructed the introitis. The use of the triangular
      perineoscrotal flap favors the vaginal and introital width, but its base should
      be close to the anal ring to prevent such a skin fold. Secondary construction of
      the labia minora was performed 27 times, and a skin reduction of the labia majora
      was performed 20 times. So far, the authors have been unable to develop a
      satisfactory method for primary construction of the labia minora. Because the
      appearance of the vulva may charge gradually during the first postoperative year,
      secondary vulvar corrections should not be performed in that period.

PMID- 10946935
TI  - Osteogenesis in cranial defects: reassessment of the concept of critical size and
      the expression of TGF-beta isoforms.
AB  - Transforming growth factor-betas (TGF-beta) have been demontstrated to be
      upregulated during osteoblast function in vitro and during cranial suture fusion
      in vivo. The authors hypothesized that spontaneous reossification of calvarial
      defects was also associated with upregulation of TGF-beta. The present study was
      designed to (1) evaluate the concept of a critical-size defect within the
      calvaria in an adult guinea pig model and (2) investigate the association between
      the ossification of calvarial defects and TGF-beta upregulation. Paired circular
      parietal defects with diameters of 3 and 5 mm and single parietal defects with
      diameters of 8 or 12 mm were made in 45 six-month-old skeletally mature guinea
      pigs. Three animals per defect size were killed after survival periods of 3 days,
      1 week, 4 weeks, 8 weeks, or 12 weeks. New bone ingrowth was evaluated by
      assessing for linear closure by a traditional linear method and by a modified
      cross-sectional area method using an image analysis system in which the thickness
      of new bone was taken into account. Immunohistochemistry was performed using
      rabbit polyclonal antibodies to localize TGF-beta1, -beta2, and -beta3. All
      specimens were photographed, and the intensity of immunostaining was graded based
      on subjective photographic assessment by three independent reviewers. No defect
      demonstrated any measurable bone replacement after a survival period of 3 days.
      All 3- and 5-mm defects were completely reossified after 12 weeks based on the
      linear analysis of new bone, indicating these defects to be less than critical
      size. However, new bone formation in the 5-mm defects never exceeded a mean of 40
      percent by cross-sectional area of new bone. Percent of new bone formation by
      cross-sectional area was significantly higher within 3-mm defects than in all
      larger defects 4 weeks after the craniotomy, reaching a mean of 89 percent new
      bone by 12 weeks. Persistent gaps were noted on linear analysis of the 8- and 12
      mm wounds by 12 weeks, and mean percent new bone by cross-sectional area remained
      below 30 percent. Immunolocalization demonstrated osteogenic fronts at the
      advancing bone edge and the endocranial side, in which the osteoblasts stained
      strongly for all isoforms of TGF-beta. The intensity of osteoblast expression
      waned considerably after the majority of the defect had reossified. These data
      indicate that histometric analysis based on cross-sectional area more accurately
      reflects the osteogenic potential of a cranial defect than does linear inspection
      of defect closure. Although the interpretation of immunolocalization studies is
      highly subjective, independent assessment by three reviewers indicates that
      isoforms of TGF-beta were upregulated during a limited "window" of time
      corresponding to the period of active calvarial reossification, and expression of
      TGF-beta corresponded to osteoblast activity within osteogenic fronts.

PMID- 10946936
TI  - Augmentation of adipofascial flaps using the long-term local delivery of insulin
      and insulin-like growth factor-1.
AB  - The adipofascial flaps currently described in the literature frequently lack the
      volume requirements for reconstructive goals. In this study, the authors examined
      the use of long-term local delivery of insulin and insulin-like growth factor-1
      (IGF-1) using polylactic-coglycolic acid/polyethylene glycol (PLGA/PEG)
      microspheres to augment inguinal adipofascial flaps based on the inferior
      epigastric vessels in the rat. Two flap models, the island flap and the limited
      dissection flap, were used to demonstrate simultaneous treatment and pretreatment
      modalities, respectively. Experimental groups received 12.5 mg of insulin
      microspheres (carrying 1 IU of insulin) plus 12.5 mg of IGF-1 microspheres
      (carrying 2.5 microg of IGF-1). A group undergoing the operation only (no
      treatment with microspheres) and a group treated with blank microspheres (no
      growth factor) served as external controls for the surgical procedure and the
      drug delivery device, respectively. In all groups (n = 5 animals in each), the
      contralateral flap served as an internal control. Upon harvest on postoperative
      day 28, the insulin and IGF-1-treated flaps in both models weighed statistically
      more than the internal control flaps and the two external control flaps.
      Likewise, on gross inspection, the adipogenic growth factor-treated flaps had
      greater volumes than the internal control flap groups and both of the external
      control flap groups (operation only and blank microspheres). Other intergroup
      comparisons suggested the absence of a systemic insulin and IGF-1 effect on
      adiposity. A histomorphometric analysis suggested (1) that insulin and IGF-1
      treatment does not alter flap cell composition and (2) that flap augmentation is
      secondary to the stimulation of cell proliferation and adipocytic differentiation
      rather than the hypertrophy of mature adipocytes. Further evidence in favor of
      cell proliferation and differentiation was the discovery of nonanatomic, ectopic
      fat islands on the pedicle sheath of the treated flaps and the lack of variation
      in cell size distribution among groups. The authors concluded that the long-term
      local delivery of insulin and IGF-1 with PLGA/PEG microspheres is an effective
      method of adipofascial flap augmentation; this method increases the number of
      mature adipocytes rather than increasing the size of preexisting cells.

PMID- 10946937
TI  - Functional and morphometric evaluation of end-to-side neurorrhaphy for muscle
      reinnervation.
AB  - This study was undertaken to quantify the effect of motor collateral sprouting in
      an end-to-side repair model allowing end organ contact. Besides documentation of
      the functional outcome of muscle reinnervation by end-to-side neurorrhaphy, this
      experimental work was performed to determine possible downgrading effects to the
      donor nerve at end organ level. In 24 female New Zealand White rabbits, the motor
      nerve branch to the rectus femoris muscle of the right hindlimb was dissected,
      cut, and sutured end-to-side to the motor branch to the vastus medialis muscle
      after creating an epineural window. The 24 rabbits were divided into two groups
      of 12 each, with the second group receiving additional crush injury of the vastus
      branch. After a period of 8 months, maximum tetanic tension in the reinnervated
      rectus femoris and the vastus medialis muscles was determined. The contralateral
      healthy side served as control. The reinnervated rectus femoris muscle showed an
      average maximum tetanic force of 24.9 N (control 26.2 N, p = 0.7827), and the
      donor- vastus medialis muscle 11.0 N (control 7.3 N, p = 0.0223). There were no
      statistically significant differences between the two experimental groups (p =
      0.9914). The average number of regenerated myelinated nerve fibers in the rectus
      femoris motor branch was 1,185 +/- 342 (control, 806 +/- 166), and the mean
      diameter was 4.6 +/- 0.6 microm (control, 9.4 +/- 1.0 microm). In the motor
      branch to the vastus medialis muscle, the mean fiber number proximal to the
      coaptation site was 1227 (+/-441), and decreased distal to the coaptation site to
      795 (+/-270). The average difference of axon counts in the donor nerve proximal
      to distal regarding the repair site was 483.7 +/- 264.2. In the contralateral
      motor branch to the vastus medialis muscle, 540 (+/- 175) myelinated nerve fibers
      were counted. In nearly all cross-section specimens of the motor branch to the
      vastus medialis muscle, altered nerve fibers could be identified in one fascicle
      distal and proximal to the repair site. The results show a relevant functional
      reinnervation by end-to-side neurorrhaphy without functional impairment of the
      donor muscle. It seems to be evident that most axons in the attached segment were
      derived from collateral sprouts. Nonetheless, the present study confirms that end
      to-side neurorrhaphy is a reliable method of reconstruction for damaged nerves,
      which should be applied clinically in a more extended manner.

PMID- 10946938
TI  - Congenital isolated absence of the nasal columella: reconstruction with an
      internal nasal vestibular skin flap and bilateral labial mucosa flaps.
AB  - Congenital aplasia of the nasal columella is a very rare anomaly. The deformity
      is characterized by the isolated absence of the columella from the nasal tip to
      the root of the philtrum, including the medial crura of the alar cartilages;
      surrounding structures such as the septum, nose, and upper lip are normal. To the
      best of our knowledge, only four such cases have been described to date. The
      embryopathogenesis for this uncommon disease is presently unknown. Our report
      describes a 14-year-old girl with congenital agenesis of the columella as an
      isolated anomaly. Her family history was positive for the presence of the same
      congenital deformity, which also affected her older brother; there was, however,
      no consanguinity between the parents. The columella defect was reconstructed with
      an internal nasal vestibular skin flap and bilateral upper labial mucosa flaps.
      There are many techniques available to repair columella defects, including free
      grafts from the ear, local flaps from the forehead, face, upper lip, and nose,
      distant flaps such as tube pedicle flaps, and free flaps from the ear. Each of
      these techniques has advantages and disadvantages. Because of this, the treatment
      of columella defects should be individualized.

PMID- 10946939
TI  - Salvage of TRAM flaps with compromised venous outflow.
AB  - A simple and effective technique is described for salvaging TRAM flaps with
      venous compromise. This has proven to be a valuable supplement to our technical
      armamentarium.

PMID- 10946940
TI  - Free transfer of expanded parascapular, latissimus dorsi, and expander "capsule"
      flap for coverage of large lower-extremity soft-tissue defect.
AB  - The coverage of large soft-tissue defects usually requires a large flap transfer,
      especially in a combination and expanded form. However, some large soft-tissue
      defects still cannot be covered by such flaps. In this article, we present a case
      of a civil war injury in a patient from Afghanistan who had severe trauma to the
      right knee, lower thigh, and upper leg and a marked soft-tissue defect. This
      large soft-tissue defect was covered with a large combined free flap of the
      expanded parascapular and latissimus dorsi muscle, including a large retrograde
      hinge flap of the tissue expander capsule and a complementary skin graft. The
      defect was covered completely, and the final result was excellent.

PMID- 10946941
TI  - Plastic surgeons in American hand surgery: the past, present, and future.

PMID- 10946942
TI  - Optimal timing of cleft palate closure.
AB  - Treatment objectives for the cleft palate patient--normal speech, normal
      maxillofacial growth, and normal hearing--are closely related. Controversy about
      the timing of cleft palate surgery is directed at the need for early palatoplasty
      for improved speech and hearing versus delayed hard palate repair for undisturbed
      facial growth. This controversy as to the value of early versus delayed closure
      continues into the present. The authors present an updated argument regarding
      this controversy along with a comprehensive literature review. They also present
      a logical algorithm based on the literature and their personal experience.

PMID- 10946943
TI  - Plastic versus cosmetic surgery: what's the difference?

PMID- 10946944
TI  - Corrugator supercilii muscle resection and migraine headaches.
AB  - This study was conducted to determine whether there is an association between the
      removal of the corrugator supercilii muscle and the elimination or significant
      improvement of migraine headaches. Questionnaires were sent to 314 consecutive
      patients who had undergone corrugator supercilii muscle resection during
      endoscopic, transpalpebral, or open forehead rejuvenation procedures. The
      patients were queried as to whether they had a history of migraine headaches and,
      if so, whether the headaches significantly improved or disappeared after surgery.
      If the answer was affirmative, then the patients were further questioned about
      the duration of the improvement or cessation of the headaches and the
      relationship to the timing of the surgery. After an initial evaluation of the
      completed questionnaires, a telephone interview was conducted to confirm the
      initial answers and to obtain further information necessary to ensure that the
      patients had a proper diagnosis based on the International Headache Society
      criteria for migraine headaches. The charts of the patients who had migraine
      headaches were studied to ascertain and classify the type of surgery they had
      undergone. Patient demographics were reviewed, and the results were statistically
      analyzed. Of the 314 patients, 265 (84.4 percent) either responded to the
      questionnaire, were interviewed, or both responded to the questionnaire and were
      interviewed. Of this group, 16 patients were excluded because of the provision of
      insufficient information to meet the International Headache Society criteria, the
      presence of organic problems, and other exclusions mandated by study design.
      Thirty-nine (15.7 percent) of the remaining 249 patients had migraine headaches
      that fulfilled the Society criteria. Thirty-one of the 39 (79.5 percent) with
      preoperative migraine noted elimination or improvement in migraine headaches
      immediately after surgery (p < 0.0001; McNemar), and the benefits lasted over a
      mean follow-up period of 47 months. When the respondents with a positive history
      of migraine headaches were further divided, 16 patients (p < 0.0001; McNemar)
      noticed improvement over a mean follow-up period of 47 months, and 15 (p <
      0.0001; McNemar) experienced total elimination of their migraine headaches over a
      mean follow-up period of 46.5 months. When divided by migraine headache type, 29
      patients (74 percent) had nonaura migraine headaches. Of these patients, the
      headaches disappeared in 11 patients, improved in 13 patients, and did not change
      in five patients (p < 0.0001). Ten patients experienced aura-type headaches,
      which disappeared or improved in seven of the patients and did not change in
      three of the patients (p < 0.0001). This study proves for the first time that
      there is indeed a strong correlation between the removal of the corrugator
      supercilii muscle and the elimination or significant improvement of migraine
      headaches.

PMID- 10946946
TI  - Biological arches and changes to the curvilinear form of the aging maxilla.
AB  - The facial skeleton can be conceptualized as a series of arches aligned along a
      vertical axis, with regional differences in shape. Previous work suggested that
      the maxilla undergoes differential growth with time. Because these arch forms
      resemble geometric forms, it may be possible to measure changes to their shape
      with the aging process. A contour analysis of the aging maxilla was undertaken.
      Computed tomographic data were assembled retrospectively. Only men were studied,
      and they were divided into two groups: young (aged 18 to 24 years; n = 6) and old
      (aged 40 to 66 years; n = 6). The computed tomography data were reconstructed
      into three-dimensional images and underwent standardization for comparison
      purposes. An axial view of the maxilla along the Frankfort horizontal was used
      for analysis. To quantify changes between curves, measurements were made of the
      vertical distance from eight equidistant points along each curve perimeter to a
      standardized baseline. Average arch forms for young and old men were then
      generated for comparison purposes. Each of the eight points along the older
      maxillary arch form existed further from the baseline than the younger arch form.
      This difference reached statistical significance at three of the eight points
      measured along the two curves. The greatest difference occurred at point 8 (p =
      .0006), which was at the medial maxilla near the nasomaxillary junction. The
      results of the study suggest that the actual contour of the maxilla undergoes
      changes as a result of the aging process. Mathematically defined idealized
      skeletal contours could help guide reconstructive surgery and aesthetic
      augmentation of the facial skeleton in the future. In addition, certain soft
      tissues of the face and torso seem to share a common shape (an alpha contour).
      This shape may also exhibit idealized forms open to quantitative analysis. The
      skeletal arch form and alpha contour most likely exhibit sexual dimorphism and
      will require further investigation. The ubiquity of the arch form in nature and
      possible implications for growth and development of the human facial skeleton are
      also discussed.

PMID- 10946945
TI  - The evaluation and management of lower eyelid retraction following cosmetic
      surgery.
AB  - Lower eyelid retraction is a common complication after cosmetic surgery of the
      lower eyelids, midface, and the adjacent face. Lower eyelid retraction is defined
      as the inferior malposition of the lower eyelid margin without eyelid eversion.
      Lower eyelid retraction presents clinically with scleral show; round, sad-looking
      eyes; lateral canthal tendon laxity; and symptoms of ocular irritation, including
      photophobia, excessive tearing, and nocturnal lagophthalmos. These patients
      frequently require ocular lubricants, including artificial tears and ointments,
      which often provide only minimal alleviation of their symptoms. The author has
      observed that lower eyelid retraction is usually accompanied by midface descent.
      On the basis of surgical observations, the causes of lower eyelid retraction seem
      to be multifactorial and include scarring between the orbital septum and
      capsulopalpebral fascia (or lower eyelid retractors), lateral canthal tendon
      laxity, and midface descent. After describing the causes of lower eyelid
      retraction, the author presents a system for evaluating patients that can assist
      the surgeon in choosing the surgical procedure(s) required to correct the lower
      eyelid malposition. The surgeon must know how to tighten a lax lateral canthal
      tendon, be familiar with the anatomy of the lower eyelid from conjunctiva to skin
      side, and know how to surgically elevate the midface. The techniques for
      correcting lower eyelid retraction are also presented. Appropriate surgery, which
      is determined on the basis of the preoperative evaluation, has allowed for the
      correction of these previously difficult-to-treat lower eyelid malpositions with
      minimal complications.

PMID- 10946947
TI  - The true hanging columella: simplified diagnosis and treatment using a modified
      direct approach.
AB  - An imbalance between the alar rim and the columella border can be a disturbing
      aesthetic deformity. If the cause is a pseudohanging columella, the therapy
      should be directed to the alar rims. When the deformity is a true hanging
      columella with unusually wide medial crural cartilages, balance can be restored
      by excising a C-shaped crescent of cartilage from the cranial border of the
      medial crura of the alar cartilages in a direct approach. This condition was
      present in approximately 15 percent of the patients reviewed. The treatment of a
      true hanging columella adds a subtle beneficial enhancement to the results of a
      rhinoplasty. The authors describe a simplified diagnostic method and present
      their experience treating the true hanging columella using a modified "direct
      approach" through a closed endonasal rhinoplasty.

PMID- 10946948
TI  - The Guastella-Mantovani septal-valve splint: an intranasal biplanar and
      multivectorial orthopedic device.
AB  - A new internal nasal device, the Guastella-Mantovani septal-valve splint, ensures
      the correct healing of the crucial area of the internal valve, simultaneously
      "centering" the septum orthopedically after nasal surgery.

PMID- 10946949
TI  - An algorithm of facial aging: verification of Lambros's theory by three
      dimensional stereolithography, with reference to the pathogenesis of midfacial
      aging, scleral show, and the lateral suborbital trough deformity.
AB  - An algorithm of facial aging is presented that serves as the conceptual basis for
      understanding aesthetic surgical principles and techniques. This model begins
      with the verification of Lambros's theory of skeletal remodeling. It was
      suggested that bony changes of the midface may be summarized as a clockwise
      rotation of the midface relative to the cranial base. Three-dimensional
      stereolithography/rapid prototyping was used to test this hypothesis. A precisely
      duplicated facial skeleton was created for young and old men (n = 12) by laser
      polymerization. Angular measurements confirmed that the angle of the pyriform and
      maxilla decreased with age (p = 0.004 and 0.005, respectively); there was a trend
      for the angle of the glabella (frontonasal angle) and orbits to do the same.
      These results validate Lambros's theory, which serves as a basis to further
      comprehend the pathogenesis of midfacial aging and the formation of ectropion and
      scleral show. The algorithm of facial aging is extrapolated from these data, from
      previous research, and from clinical observation. This model encompasses three
      main concepts or tenets, and it may serve as a clinical tool for the diagnosis
      and treatment of facial aging.

PMID- 10946950
TI  - Evaluating breast parenchymal maldistribution with regard to mastopexy and
      augmentation mammaplasty.

PMID- 10946951
TI  - A paradigm shift for plastic surgeons: no longer focusing on excising skin
      excess.

PMID- 10946952
TI  - Woe for HMO.

PMID- 10946953
TI  - Exogenous growth factors and cytokines in tendon surgery.

PMID- 10946954
TI  - Soft-tissue reconstruction following debridement for chronic osteomyelitis of the
      lower limb.

PMID- 10946956
TI  - An improved tie-over dressing technique for skin grafts using a hydrocellular
      dressing.

PMID- 10946955
TI  - The future of liposuction and fat.

PMID- 10946957
TI  - Partial-thickness sponge dressing of facial skin grafts.

PMID- 10946958
TI  - Criss-cross scoring of postburn necrotic tissue.

PMID- 10946959
TI  - Ear reconstruction supported by a stereolithographic model.

PMID- 10946960
TI  - Polyurethane film (opsite) for superficial fingertip avulsion injuries.

PMID- 10946961
TI  - Current trends in breast reduction.

PMID- 10946962
TI  - Diffuse microscopic intransit metastases from malignant melanoma of the breast.

PMID- 10946963
TI  - Angiogenesis in primary tumor cells of metastatic and nonmetastatic malignant
      melanoma.

PMID- 10946965
TI  - Maintaining the privacy of patients.

PMID- 10946964
TI  - Lymphatic mapping and sentinel lymph node basin after sentinel lymph node biopsy
      for melanoma.

PMID- 10946966
TI  - Creating long-term benefits in cleft lip and palate volunteer missions.

PMID- 10946967
TI  - Creating long-term benefits in cleft lip and palate volunteer missions.

PMID- 10946969
TI  - Use of the one-finger glove for rat anesthesia.

PMID- 10946968
TI  - Plastic surgery of the face in Byzantium in the fourth century.

PMID- 10946970
TI  - A new dyeing method to facilitate dissection.

PMID- 10946971
TI  - Protective effect of chili against autocannibalism.

PMID- 10946972
TI  - Comparison between 99mTc-tetrofosmin/pertechnetate subtraction scintigraphy and
      99mTc-tetrofosmin SPECT for preoperative localization of parathyroid adenoma in
      an endemic goiter area.
AB  - RATIONALE AND OBJECTIVES: Technetium-99m-((99m)Tc-) tetrofosmin, a cationic,
      lipophilic complex like (99m)Tc-sestamibi, has proved to be a potential tracer
      for parathyroid scintigraphy despite some differences in washout behavior from
      the thyroid gland. Previous results comparing a double-phase technique with
      single-proton emission computed tomography (SPECT) or with subtraction techniques
      demonstrated a high detection rate, especially when SPECT and subtraction
      techniques were used, whereas the double-phase protocol revealed only moderate
      results. In this study, a direct comparison was made between (99m)Tc
      tetrofosmin/pertechnetate subtraction and SPECT to elucidate the optimal protocol
      for tetrofosmin parathyroid imaging. METHODS: Twenty-three patients who were
      biochemically suspected of parathyroid adenoma or hyperplasia due to primary or
      tertiary hyperparathyroidism were included in our study. In all patients, serum
      calcium, phosphate, and intact parathormone levels were analyzed in a single
      blood sample before (99m)Tc-tetrofosmin/pertechnetate subtraction scintigraphy
      and SPECT. Ultrasound of the neck was performed in all patients to exclude false
      positive results due to thyroid adenomas. All patients underwent
      parathyroidectomy with intraoperative revision of all parathyroid glands, and the
      histological results were compared with preoperative findings. RESULTS: Both
      imaging modalities, ie, subtraction scintigraphy and SPECT, correctly identified
      20 of 23 (87%) histologically confirmed adenomas preoperatively. The positive
      predictive value was calculated to be 95% and 100%, respectively, for these two
      methods. Subtraction scintigraphy and SPECT showed concordant results in 19
      patients (18 positive, 1 false-negative) and discordant results in 4 patients (2
      positive with subtraction, 2 with SPECT). The combined use of subtraction
      scintigraphy and SPECT techniques revealed a sensitivity of 95.7% (22/23) and a
      positive predictive value of 95%. The whole procedure can be performed in less
      than 90 minutes per patient. Whereas subtraction scintigraphy tended to show more
      false-positive retentions due to thyroid adenomas, the interpretation of SPECT
      may be difficult in small adenomas with missing thyroid/parathyroid differential
      washout. CONCLUSIONS: Both imaging modalities, subtraction scintigraphy with
      pertechnetate and SPECT, are highly sensitive methods for parathyroid adenoma
      localization with (99m)Tc-tetrofosmin. However, our study did demonstrate that a
      combination of both modalities can further improve the diagnostic accuracy.
      Especially in an endemic goiter area, additional ultrasound may be required to
      avoid false-positive results due to thyroid adenomas.

PMID- 10946973
TI  - Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe
      hereditable hyperlipidemic rabbits.
AB  - RATIONALE AND OBJECTIVES: Inflammatory atherosclerotic plaques are characterized
      by increased endothelial permeability and multiple macrophages. Blood-pool MRI
      contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the
      monocyte-macrophage system and thus, may label inflammatory plaques. The
      objective was to demonstrate SPIO uptake in plaques of atherosclerotic rabbits by
      MRI and histology. METHODS: Aortas of anesthetized Watanabe hereditable
      hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo
      sequence at 1.5 T. Four groups of five animals each were studied: (1) without
      ultrasmall SPIO (carboxydextran coating; particle size, 25 nm; estimated plasma
      half-life, 6 hours) or with imaging after intravenous injection of SPIO at a dose
      (micromol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), or
      200/48 (4). In vivo MRI was compared with corresponding ex vivo histological iron
      stains. RESULTS: Animals receiving 200 micromol Fe/kg demonstrated areas of focal
      signal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/-
      11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in controls (P =
      0.009). The number of images with this finding in groups 2 and 3 was not
      significantly different compared with controls. By microscopy, SPIO-iron was seen
      in the endothelial cells and subendothelial intimal macrophages of
      atherosclerosis-prone aortic wall segments. Atherosclerotic lesions demonstrating
      iron uptake also showed a high macrophage content. CONCLUSIONS: SPIO accumulates
      in aortic plaques of atherosclerotic rabbits, producing a characteristic MRI
      finding. As SPIO accumulates in plaques with increased endothelial permeability
      and a high macrophage content, two established features of plaque inflammation,
      it may have a potential for noninvasive assessment of inflammatory
      atherosclerotic plaques.

PMID- 10946975
TI  - Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging.
AB  - RATIONALE AND OBJECTIVES: To evaluate the efficacy of a novel tumor receptor
      specific small-peptide-near-infrared dye conjugate for tumor detection by optical
      imaging. METHODS: A novel, near-infrared dye-peptide conjugate was synthesized
      and evaluated for tumor-targeting efficacy in a well-characterized rat tumor
      model (CA20948) known to express receptors for the chosen peptide. A simple
      continuous-wave optical imaging system, consisting of a near-infrared laser
      diode, a cooled CCD camera, and an interference filter, was used in this study.
      RESULTS: Tumor retention of two non-tumor-specific dyes, indocyanine green and
      its derivatized analogue, bis-propanoic acid cyanine dye (cypate), was
      negligible. In contrast, the receptor-specific peptide-cypate conjugate (cytate)
      was retained in the CA20948 tumor, with an excellent tumor-tonormal-tissue ratio
      in the six rats examined. CONCLUSIONS: Optical detection of tumors with a
      receptor-targeted fluorescent contrast agent has been demonstrated. This result
      represents a new direction in cancer diagnosis and patient management.

PMID- 10946974
TI  - Nitric oxide protects against contrast media-increased pulmonary vascular
      permeability in rats.
AB  - RATIONALE AND OBJECTIVES: Nitric oxide (NO) regulation of endothelial function is
      involved in the development of acute lung injury. The role of NO in contrast
      media-induced increases in pulmonary vascular permeability was investigated in a
      rat model. METHODS: Nonionic (iohexol) and ionic (ioxaglate) contrast media were
      intravenously injected at 1.5 mL/min in rats. Pulmonary vascular permeability was
      evaluated by measuring the amount of Evans blue dye uptake as a quantitative
      marker of albumin extravasation in lung tissue. RESULTS: Intravenous injections
      of contrast media at doses of 4 and 6 g I/kg induced a dose-dependent increase in
      pulmonary vascular permeability. L-Arginine (an NO synthase substrate) and N(G)
      nitro-L-arginine (L-NNA) (an NO synthase inhibitor) prevented and aggravated,
      respectively, the increase in pulmonary vascular permeability induced by the
      contrast medium. An aggravating action of L-NNA was confirmed by morphological
      and histological observations, this action being blocked by L-arginine (300
      mg/kg) but not by D-arginine. Isosorbide dinitrate (1-20 mg/kg), an NO donor, had
      a dose-dependent protective effect on ioxaglate-increased vascular permeability.
      CONCLUSIONS: Our experimental findings suggest that contrast media at high doses
      produce pulmonary edema by inhibiting endothelial NO production, and
      nitrovasodilators protect against this adverse effect in rats.

PMID- 10946976
TI  - Timing of the hepatic arterial phase during contrast-enhanced computed tomography
      of the liver: assessment of normal values in 25 volunteers.
AB  - OBJECTIVES: To define normal values of the beginning and duration of the hepatic
      arterial phase (HAP) during contrast-enhanced computed tomography (CT). METHODS:
      Twenty-five volunteers (16 men, 9 women; mean age, 60.0 years) without history or
      suspicion of liver disease were examined with dynamic single-section CT. Scanning
      was performed at a single level that included the liver, aorta, and portal vein.
      A series of 25 scans was obtained over a period of 88 seconds (1 baseline scan
      followed by 16 scans every 2 seconds and 8 scans every 7 seconds) beginning with
      the injection of a bolus of contrast agent (40 mL, 10 mL/s) and a 40-mL NaCl
      bolus chaser. Contrast enhancement in the liver, aorta, and portal vein was
      measured with regions of interest, and time-density curves were obtained. These
      data were processed with a pharmacodynamic fitting program and the duration of
      the HAP was calculated. The onsets of the HAP and the portal venous phase were
      assessed as lag times, referring to the beginning of enhancement in the abdominal
      aorta. RESULTS: The mean lag time of the HAP was 5.4 seconds after the aorta and
      the mean duration was 8.6 seconds. The mean lag time of the portal venous phase
      was 13.9 seconds after the aorta. CONCLUSIONS: These data can be used to optimize
      protocols for routine CT. Because of the short duration of the HAP, imaging of
      the entire liver during this phase is possible only with multidetector CT
      scanners.

PMID- 10946977
TI  - Prevention of the hemodynamic effects of iopromide-carrying liposomes in rats and
      pigs.
AB  - RATIONALE AND OBJECTIVES: Intravenous injection of liposomes is able to trigger
      allergy-like reactions that affect the cardiopulmonary system. The mechanism of
      these effects is still not totally clear. Because prediction of adverse reactions
      and the consequent exclusion of reactive patients do not seem feasible,
      prevention might have a considerable impact. METHODS: Two small, multilamellar
      liposome batches with the encapsulated contrast agent iopromide, which differed
      by size and buffer composition, were injected into anesthetized rats (n = 5 per
      group) and pigs (n = 6 per group). Blood pressure (BP), cardiac output (CO),
      contractility (dP/dt; in rats), total peripheral resistance (TPR; in rats),
      pulmonary vascular resistance (in pigs), and pulmonary arterial pressure (PAP; in
      pigs) were monitored. Saline, mannitol solution, the two buffers, and the
      contrast medium were used as controls. RESULTS: Significant changes in
      hemodynamic parameters were observed not only between liposomes and controls but
      also between the two liposome preparations. In rats, a significant decrease in BP
      followed by its normalization and subsequent increase, a decrease in CO followed
      by an increase, a decrease in TPR, and a decrease in dP/dt followed by an
      increase were observed. In pigs, the effects were different both in quality and
      in quantity (more intense) compared with those in rats. In this species, an
      increase in BP, a decrease in CO, an increase in TPR, and an increase in PAP were
      found. Pretreatment with acetylsalicylic acid was able to prevent the hemodynamic
      changes induced by the liposomes. CONCLUSIONS: Allergy-like side effects induced
      by liposome injection strongly depend on the size, electric charge, and
      composition of the particles. The mechanism triggered by liposome injection
      probably is complex and can be effectively blocked by pretreatment with
      acetylsalicylic acid.

PMID- 10946978
TI  - Feasibility and utility of respiratory-gated, gadolinium-enhanced T1-weighted
      magnetic resonance urography in children.
AB  - RATIONALE AND OBJECTIVES: To evaluate the feasibility and utility of respiratory
      gated, gadolinium-enhanced T1-weighted magnetic resonance (MR) urography in
      children. METHODS: In a prospective study, 30 consecutive children, aged 3 weeks
      to 13.8 years, underwent MR urography. After intravenous injection of low-dose
      furosemide and gadopentetate dimeglumine, respiratory-gated, coronal, T1-weighted
      3D-gradient-echo sequences were obtained at 1.5 T 5 to 30 minutes after contrast
      administration. Postprocessing of the data was performed using a maximum
      intensity projection algorithm. In addition, precontrast half-Fourier rapid
      acquisition with relaxation enhancement MR urograms were obtained in 29 children.
      RESULTS: Respiratory-gated, T1-weighted MR urography was successfully performed
      in all children without the need for sedation. Compared with the final diagnosis,
      prospective analysis of MR urography images revealed the correct diagnosis in 56
      of 58 pelvicaliceal systems (96%). The ureteral morphology was correctly
      evaluated in 59 of 64 ureters (92%). The method showed limited efficiency for
      evaluating nonfunctioning renal units. CONCLUSIONS: Respiratory-gated, gadolinium
      enhanced T1-weighted MR urography is a feasible and effective diagnostic tool in
      the assessment of upper urinary tract morphology in children. It is especially
      useful in depicting nondilated collecting systems and ureters.

PMID- 10946979
TI  - Robotic system for biopsy and therapy of breast lesions in a high-field whole
      body magnetic resonance tomography unit.
AB  - RATIONALE AND OBJECTIVES: With magnetic resonance mammography, significant
      progress has been achieved in the diagnosis of small breast cancers. However,
      biopsy and therapy of suspicious lesions must take place at a later time.
      Diagnosis and simultaneous biopsy and therapy in one single examination would
      considerably reduce costs, strain on the patient, and side effects. METHODS:
      ROBITOM (Robotic system for biopsy and interventional therapy of mammary lesions)
      is used to approach a lesion found in the breast in an image-controlled manner
      under a high magnetic field (eg, 1.5 T). The robotic system works in the direct
      vicinity of the isocenter of a magnet and consists of a trocar, coaxial sleeve,
      biopsy needle, laser applicator, and a control and driving unit. It contains a
      rack, a driving unit along the three coaxes of space, and a gripping unit for
      instruments or biopsy sample removal. The system has six degrees of freedom.
      RESULTS: In vitro experiments in pig liver including eight targets (vitamin E
      capsules, 4 mm in diameter) were performed. All eight capsules were hit precisely
      by the robotic biopsy system. The procedure was performed directly in the
      isocenter of a 1.5-T whole-body scanner. CONCLUSIONS: The system allows the
      coordinates of a lesion in the breast to be approached in a high magnetic field
      without shifting the patient. A combination of imaging with biopsy and subsequent
      therapy (eg, laser therapy or cryotherapy) seems to be feasible in the future.

PMID- 10946980
TI  - Dry eye: towards a new understanding.

PMID- 10946981
TI  - Broad spectrum antimicrobial activity of a new multi-purpose disinfecting
      solution.
AB  - PURPOSE: There has been increasing awareness of the need for more powerful
      contact lens disinfectants, ideally having low toxicity and allergenicity to
      ocular tissue. Opti-Free Express with ALDOX Multi-Purpose Disinfecting Solution
      (MPDS) was recently marketed as a new multi-purpose disinfecting solution for
      soft contact lenses. MPDS contains two antimicrobial agents, polyquaternium-1 and
      myristamidopropyl dimethylamine, to broaden the range of antimicrobial activity.
      The purpose of this study was to evaluate the antimicrobial activity of MPDS
      against microorganisms that have been reported as contact lens and lens case
      contaminants and causative agents of microbial keratitis. METHODS: MPDS was
      challenged with high numbers of gram-positive and gram-negative bacteria, yeast,
      mold, and Acanthamoeba. Several lots of product were challenged with at least
      three separate inocula of each isolate. After exposure to the disinfecting
      solution, a sample was removed from the product and plated for survivors by
      suitable recovery methods. The plates were incubated and the number of survivors
      was enumerated. RESULTS: The results showed that MPDS was bactericidal,
      fungicidal and amoebicidal against an extensive variety of environmental
      contaminants of lens care accessories and ocular pathogens. MPDS was capable of
      killing a broad spectrum of microorganisms. The log reduction exceeded the
      primary criteria for disinfecting products and produced a notable reduction of
      other clinical and environmental isolates as well. CONCLUSIONS: Opti-Free Express
      MPDS contains antimicrobial agents that can kill an extensive spectrum of many
      different types of microorganisms that may contaminate contact lenses and
      solutions.

PMID- 10946982
TI  - Disposable contact lenses in penetrating keratoplasty.
AB  - PURPOSE: To evaluate the therapeutic efficacy of disposable contact lenses in
      management of complications after keratoplasty. METHODS: Twenty-eight patients
      with various post keratoplasty complications were fit with disposable contact
      lenses (45% Vifilcon A and 55% water content). Indications for lens use included
      persistent epithelial defects, wound leak, graft edema, dry eye and protection of
      normal corneal epithelium. RESULTS: Success was obtained with the therapeutic use
      of disposable lenses in 20 of the 28 cases. The best results were seen in
      maintenance and restoration of healthy ocular surface and small wound leaks.
      Stromal graft edema with no epithelial involvement was the major area of
      therapeutic failure. CONCLUSIONS: Disposable contact lenses are an attractive low
      cost option in the management of complications after keratoplasty. They are
      particularly useful in maintaining a healthy ocular surface, providing
      symptomatic relief and avoiding resurgery in patients with small wound leaks.

PMID- 10946983
TI  - The effects of one-hour wear of high-Dk soft contact lenses on corneal pH and
      epithelial permeability.
AB  - PURPOSE: Previous studies have shown that 1-hour closed-eye contact lens wear
      with a low-Dk lens causes a significant reduction in corneal pH and an increase
      in epithelial permeability. In the present study, we evaluated the effects of
      super-high-Dk/t soft lenses on corneal epithelial barrier function and stromal
      pH. METHODS: Corneal thickness was measured by optical pachometry, while
      epithelial permeability and stromal pH were measured by fluorophotometry. A
      paired-eye design was used in which one eye was randomly allocated to wear a high
      oxygen-permeable soft lens (CIBAVision Focus/NIGHT & DAY (Dk/t= 175) while the
      other eye did not wear a lens. RESULTS: After 1-hour closed-eye lens wear,
      neither the difference in corneal swelling (P = 0.206) nor the permeability (P =
      0.055) between both eyes was significantly different. The mean pH values under
      open-eye conditions were 7.66 vs. 7.57 for the treatment and control eyes,
      respectively (P = 0.082), dropping to 7.27 vs. 7.25 after 1-hour eye closure (P =
      0.283). CONCLUSIONS: Although our results are limited to a 1-hour observation
      period, they do provide evidence that high-Dk materials may eliminate corneal
      acidosis and reduced epithelial barrier function that accompany closed-eye
      contact lens wear with lower-Dk soft lens materials.

PMID- 10946984
TI  - Evaluation of the PuriLens contact lens care system: an automatic care system
      incorporating UV disinfection and hydrodynamic shear cleaning.
AB  - PURPOSE: This study evaluates lens care using the PuriLens System, an advanced
      way to clean and disinfect soft hydrophilic lenses using subsonic agitation and
      UV radiation, respectively. METHODS: A two-period crossover lens cleaning and
      safety investigation was conducted using 80 patients. Disinfecting efficacy was
      tested in accordance with standard FDA protocols. Lens compatibility was studied
      with Group I and Group IV lenses during the equivalent of a 6-month care regimen
      by measuring: lens power, base curve, wet diameter, refractive index, clarity,
      and tint. Safety was evaluated through slit-lamp findings, wearing time, comfort,
      and visual acuity. RESULTS: The mean wearing time of patients in the study was
      13.79 hours. No slit lamp findings greater than grade 2 were noted. Visual acuity
      was 20/25 or better in 92.5% of examinations. None of the patients lost more than
      two lines of acuity. Lens surface evaluation showed no deposits (grade 0) to very
      slight deposits (grade 1) in 94.4% of examinations. Lenses cleaned with the
      PuriLens System were cleaner by a statistically significant margin (P=0.02)
      compared to lenses digitally cleaned with a leading multi-purpose solution (ReNu,
      Bausch & Lomb). Overall, neither the Group I nor Group IV lenses were affected
      after 180 cleaning cycles. CONCLUSIONS: The PuriLens System provides automatic
      lens care compliance, superior antimicrobial efficacy, and eliminates the need
      for daily digital cleaning.

PMID- 10946985
TI  - 1-Day Acuvue vs. Focus Dailies: a comparison of comfort, user preference, and
      incidence of corneal complications.
AB  - PURPOSE: Two types of daily disposable soft contact lenses, 1-Day Acuvue (Johnson
      & Johnson K.K., Japan) and Focus Dailies (CIBA Vision Corp.), were compared for
      comfort, user preference, and any associated incidence of corneal complications.
      METHODS: 1-Day Acuvue and Focus Dailies were randomly prescribed for one eye each
      of 127 contact lens wearers. After 1 week of lens wear, user preference, anterior
      segment health, and tear film stability on the contact lenses were evaluated.
      RESULTS: Group A consisted of 45 subjects who had been wearing 1-Day Acuvue prior
      to the study and group B consisted of 82 subjects who had been wearing other
      types of soft contact lenses prior to the study. A statistically significant
      number of subjects in both group A and group B preferred 1-Day Acuvue. In group A
      there were significantly fewer corneal complications in the eyes with 1-Day
      Acuvue than in the eyes with Dailies. However, there was no difference in the
      incidence of corneal complications in group B. CONCLUSIONS: If Dailies are
      prescribed for current 1-Day Acuvue wearers, extra care may be required. 1-Day
      Acuvue lenses could be prescribed successfully for those who previously wore soft
      contact lenses other than 1-Day Acuvue.

PMID- 10946986
TI  - Endothelial cell density of the cornea during rigid gas permeable contact lens
      wear.
AB  - PURPOSE: To determine the influence of a daily wear rigid gas permeable (RGP)
      high DK lens (CIBA Vision Persecon92E, Dk=92 x 10(-11)) on corneal endothelial
      cell density (ECD). METHODS: A prospective longitudinal, follow-up study was
      conducted. Variations in corneal ECD during the first year were reported. For
      this purpose, the endothelium of 97 eyes of 57 unadapted subjects were compared
      by specular microscopy before and after 1 week (n= 74), 1 month (n=67), 3 months
      (n=51), and 1 year (n=23) of wearing contact lenses. RESULTS: There was a
      significant decrease in cell density vs age (r=-0.28, P=0.005). ECD significantly
      increased 1 week (3.6%) (P=0.001), 1 month (3.6%) (P=-0.003), and 3 months (4.5%)
      (P=0.003) after contact lens wear. One year after the lens fitting, a similar but
      not significant increase was found. While ECD increase was insignificant with
      initially high ECD subjects (>2700 cells/mm2), subjects with low ECD initially
      (<2700 cells/mm2) showed a significant increase in ECD in all time intervals.
      CONCLUSIONS: In the 1 week RGP contact lens wearing period, the endotheliums with
      low ECD probably adapted to a new oxygen environment by cell migration or mitotic
      activity. The increased ECD was perhaps related to the daily wear schedule in
      which the oxygen partial pressure was sufficient.

PMID- 10946987
TI  - Intraoperative PAR corneal topography system (CTS): comparison of its
      keratometric readings to manual keratometer, auto-keratometer, EyeSys Corneal
      Analysis system, and slit lamp PAR CTS in healthy eyes.
AB  - PURPOSE: To compare the keratometric readings obtained from Intraoperative PAR
      Corneal Topography System (IOPAR) to those produced by manual keratometer (Mnl
      Km), autokeratometer (Auto-Km), EyeSys CAS (EyeSys Corneal Analysis System) and
      slit lamp PAR CTS in healthy eyes. METHODS: All instruments were calibrated prior
      to use and only data from the best image obtained was used for statistical
      analysis. Simulated keratometry readings obtained from the central 3-mm zone of
      the corneas by IOPAR, including flat (K1) and steep (K2) keratometry readings,
      average keratometric power (AK), astigmatism (As) (difference between steep and
      flat keratometry readings) and the axis of the steep meridian (Ax) were compared
      to those from four other units. The latter units were also compared among
      themselves. Statistical analysis was done for right and left eyes separately. For
      each variable, average differences between the measurements taken from pairs of
      instruments were estimated, with corresponding 95% confidence intervals. The
      degree of agreement between pairs of instruments on individual measurements was
      additionally assessed, via the use of "Bland-Altman"-type plots, and estimates of
      the proportion of cases achieving satisfactory agreement. Additionally, for every
      variable, the average of the measurements taken from the different instruments
      were compared. RESULTS: Forty-five (22 right and 23 left) normal corneas of 26
      volunteers were examined. On the average, IOPAR tended to measure K1 higher than
      slit lamp PAR CTS system. Because K2 measurements taken by the IOPAR were higher
      than that of all other instruments, the As measurements, on the average, were
      also higher than that of others, with the exception of the PAR CTS. For the same
      reasons, the IOPAR produced average AK readings that were higher than those taken
      by EyeSys CAS and PAR CTS. When the individual measurements taken by the IOPAR
      were compared with each of the other units, according to the arbitrary
      designation of satisfactory agreement within +/-0.5 D (for K1, K2, AK, and As)
      and +/-20 degrees (for Ax), for almost all parameters, proportion of differences
      that were within the agreement range varied from 0.33 to 0.82, with wide
      confidence intervals (confidence interval lower limits ranging from 0.20 to 0.61
      and upper limits ranging from 0.62 to 0.94). CONCLUSIONS: IOPAR is a clinically
      useful topographic system, producing qualitative and quantitative data in the
      operating environment that, in normal corneas, on the average, matches those
      produced by the other units in the clinic. When individually analyzed, its
      keratometric measurements may show greater variations with respect to other
      units. Further studies with multiple examiners, in corneas with high or irregular
      astigmatism are required to establish its reproducibility and efficacy.

PMID- 10946988
TI  - Why the eye becomes dry: a cornea and lacrimal gland feedback model.
AB  - PURPOSE: Many explanations have been offered for why a large segment of the
      population develops dry eye. The purpose of this paper is to describe a new
      unifying theory of dry eye that incorporates all of these causes. METHODS: Data
      from the Department of Ophthalmology, University of Iowa Hospitals and Clinics
      was analyzed from 520 patients with dry eye, blepharitis and other conditions to
      assess the relationship between dry eye and blepharitis. This data was reviewed
      in terms of the relationship between dry eye, menopause, and aging. Also examined
      in detail were many of the proposed causes for dry eye in the literature.
      RESULTS: A close relationship between corneal damage and lacrimal gland function
      is hypothesized. Not only does decreased lacrimal gland output damage the ocular
      surface, but also damage to the corneal surface creates a negative feedback loop
      and damage to the lacrimal gland. There are probably several mechanisms by which
      this feedback occurs. One mechanism results from interruption or damage to the
      sensory corneal nerves. Damage to the nerves within the lacrimal gland may be
      another mechanism. Alteration of growth factor levels in the lacrimal gland,
      which occurs following corneal damage, represents another possible mechanism.
      Contact lenses and corneal refractive surgery are additional elements that may
      create negative feedback to the lacrimal gland. CONCLUSION: The ocular surface
      and the lacrimal gland functions as a tightly integrated unit. Dry eye conditions
      damage the ocular surface and this in turn leads to further damage to the
      lacrimal gland.

PMID- 10946989
TI  - Fungal keratitis in a soft contact lens wearer.
AB  - PURPOSE: To describe a case of fungal keratitis in a soft contact lens wearer.
      METHODS AND RESULTS: A 57 year old female, compliant, frequent replacement soft
      contact lens wearer, with a possible prior history of herpes simplex keratitis,
      presented with pain and injection of her left eye of four weeks duration. Gram
      stain of a corneal ulcer of the left eye revealed fungal organisms and cultures
      grew Fusarium solani. The infiltrate responded to topical and systemic antifungal
      agents, but a corneal perforation developed which required a therapeutic
      penetrating keratoplasty. CONCLUSIONS: Fungal infections are a cause of corneal
      ulcers in contact lens wearers. Despite the use of topical and systemic
      antifungal agents, fungal ulcers frequently require surgical intervention.

PMID- 10946990
TI  - A temporal mechanism for generating the phase precession of hippocampal place
      cells.
AB  - The phase relationship between the activity of hippocampal place cells and the
      hippocampal theta rhythm systematically processes as the animal runs through the
      region in an environment called the place field of the cell. We present a minimal
      biophysical model of the phase precession of place cells in region CA3 of the
      hippocampus. The model describes the dynamics of two coupled point neurons-
      namely, a pyramidal cell and an interneuron, the latter of which is driven by a
      pacemaker input. Outside of the place field, the network displays a stable,
      background firing pattern that is locked to the theta rhythm. The pacemaker input
      drives the interneuron, which in turn activates the pyramidal cell. A single
      stimulus to the pyramidal cell from the dentate gyrus, simulating entrance into
      the place field, reorganizes the functional roles of the cells in the network for
      a number of cycles of the theta rhythm. In the reorganized network, the pyramidal
      cell drives the interneuron at a higher frequency than the theta frequency, thus
      causing a systematic precession relative to the theta input. The frequency of the
      pyramidal cell can vary to account for changes in the animal's running speed. The
      transient dynamics end after up to 360 degrees of phase precession when the
      pacemaker input to the interneuron occurs at a phase to return the network to the
      stable background firing pattern, thus signaling the end of the place field. Our
      model, in contrast to others, reports that phase precession is a temporally, and
      not spatially, controlled process. We also predict that like pyramidal cells,
      interneurons phase precess. Our model provides a mechanism for shutting off place
      cell firing after the animal has crossed the place field, and it explains the
      observed nearly 360 degrees of phase precession. We also describe how this model
      is consistent with a proposed autoassociative memory role of the CA3 region.

PMID- 10946991
TI  - Comparison of alternative designs for reducing complex neurons to equivalent
      cables.
AB  - Reduction of the morphological complexity of actual neurons into accurate,
      computationally efficient surrogate models is an important problem in
      computational neuroscience. The present work explores the use of two
      morphoelectrotonic transformations, somatofugal voltage attenuation (AT cables)
      and signal propagation delay (DL cables), as bases for construction of
      electrotonically equivalent cable models of neurons. In theory, the AT and DL
      cables should provide more accurate lumping of membrane regions that have the
      same transmembrane potential than the familiar equivalent cables that are based
      only on somatofugal electrotonic distance (LM cables). In practice, AT and DL
      cables indeed provided more accurate simulations of the somatic transient
      responses produced by fully branched neuron models than LM cables. This was the
      case in the presence of a somatic shunt as well as when membrane resistivity was
      uniform.

PMID- 10946992
TI  - Synchronous clusters in a noisy inhibitory neural network.
AB  - We study the stability and information encoding capacity of synchronized states
      in a neuronal network model that represents part of thalamic circuitry. Our model
      neurons have a Hodgkin-Huxley-type low-threshold calcium channel, display
      postinhibitory rebound, and are connected via GABAergic inhibitory synapses. We
      find that there is a threshold in synaptic strength, tau(c), below which there
      are no stable spiking network states. Above threshold the stable spiking state is
      a cluster state, where different groups of neurons fire consecutively, and each
      neuron fires with the same cluster each time. Weak noise destabilizes this state,
      but stronger noise drives the system into a different, self-organized,
      stochastically synchronized state. Neuronal firing is still organized in
      clusters, but individual neurons can hop from cluster to cluster. Noise can
      actually induce and sustain such a state below the threshold of synaptic
      strength. We do find a qualitative difference in the firing patterns between
      small (approximately 10 neurons) and large (approximately 1000 neurons) networks.
      We determine the information content of the spike trains in terms of two separate
      contributions: the spike-time jitter around cluster firing times, and the hopping
      from cluster to cluster. We quantify the information loss due to temporally
      correlated interspike intervals. Recent experiments on the locust olfactory
      system and striatal neurons suggest that the nervous system may actually use
      these two channels to encode separate and unique information.

PMID- 10946993
TI  - Computational consequences of temporally asymmetric learning rules: II. Sensory
      image cancellation.
AB  - The electrosensory lateral line lobe (ELL) of mormyrid electric fish is a
      cerebellum-like structure that receives primary afferent input from
      electroreceptors in the skin. Purkinje-like cells in ELL store and retrieve a
      temporally precise negative image of prior sensory input. The stored image is
      derived from the association of centrally originating predictive signals with
      peripherally originating sensory input. The predictive signals are probably
      conveyed by parallel fibers. Recent in vitro experiments have demonstrated that
      pairing parallel fiber-evoked excitatory postsynaptic potentials (epsps) with
      postsynaptic spikes in Purkinje-like cells depresses the strength of these
      synapses. The depression has a tight dependence on the temporal order of pre- and
      postsynaptic events. The postsynaptic spike must follow the onset of the epsp
      within a window of about 60 msec for the depression to occur and pairings at
      other delays yield a nonassociative enhancement of the epsp. Mathematical
      analyses and computer simulations are used here to test the hypothesis that
      synaptic plasticity of the type established in vitro could be responsible for the
      storage of temporal patterns that is observed in vivo. This hypothesis is
      confirmed. The temporally asymmetric learning rule established in vitro results
      in the storage of activity patterns as observed in vivo and does so with
      significantly greater fidelity than other types of learning rules. The results
      demonstrate the importance of precise timing in pre- and postsynaptic activity
      for accurate storage of temporal information.

PMID- 10946995
TI  - Incorporation of conformationally constrained beta-amino acids into peptides.
AB  - The use of norbornene units to induce the formation of beta-sheet and beta-turn
      type structures in peptides is discussed. The norbornene unit is readily prepared
      by a desymmetrization reaction and is easily incorporated into a peptide chain.
      Depending upon the exact nature of the norbornene unit, it is possible to form
      structures which resemble parallel beta-sheets, antiparallel beta-sheets or beta
      turns. Similar peptide analogues incorporating a cis-2-amino-cyclopropane
      carboxylic acid unit can also be prepared. As an illustration of the application
      of this chemistry, a short, asymmetric synthesis of conformationally constrained
      metalloprotease inhibitors is presented.

PMID- 10946994
TI  - Robust spectrotemporal reverse correlation for the auditory system: optimizing
      stimulus design.
AB  - The spectrotemporal receptive field (STRF) is a functional descriptor of the
      linear processing of time-varying acoustic spectra by the auditory system. By
      cross-correlating sustained neuronal activity with the dynamic spectrum of a
      spectrotemporally rich stimulus ensemble, one obtains an estimate of the STRF. In
      this article, the relationship between the spectrotemporal structure of any given
      stimulus and the quality of the STRF estimate is explored and exploited. Invoking
      the Fourier theorem, arbitrary dynamic spectra are described as sums of basic
      sinusoidal components--that is, moving ripples. Accurate estimation is found to
      be especially reliant on the prominence of components whose spectral and temporal
      characteristics are of relevance to the auditory locus under study and is
      sensitive to the phase relationships between components with identical temporal
      signatures. These and other observations have guided the development and use of
      stimuli with deterministic dynamic spectra composed of the superposition of many
      temporally orthogonal moving ripples having a restricted, relevant range of
      spectral scales and temporal rates. The method, termed sum-of-ripples, is similar
      in spirit to the white-noise approach but enjoys the same practical advantages-
      which equate to faster and more accurate estimation--attributable to the time
      domain sum-of-sinusoids method previously employed in vision research.
      Application of the method is exemplified with both modeled data and experimental
      data from ferret primary auditory cortex (AI).

PMID- 10946996
TI  - Solid-phase synthesis of chemotactic peptides using alpha-azido acids.
AB  - Four chemotactic peptides, For-Met-Xxx-Phe-OMe, with an alpha,alpha-disubstituted
      amino acid at position 2 have been synthesized by the azido acid method [Meldal
      M, Juliano MA, Jansson AM. 1997. Azido acids in a novel method of solid-phase
      peptide synthesis. Tetrahedron Lett. 38: 2531-2534] on solid-phase, and were
      tested for biological activity. Dipropylglycine in the central position (Xxx) was
      found to be as active as the natural chemotactic peptide for chemotactic activity
      toward human neutrophils. Higher yields were obtained than previously reported
      solution-phase syntheses of chemotactic peptides, and EEDQ was used successfully
      for the difficult solid-phase formylation of amino groups.

PMID- 10946997
TI  - Potent cyclic monomeric and dimeric peptide inhibitors of VLA-4 (alpha4beta1
      integrin)-mediated cell adhesion based on the Ile-Leu-Asp-Val tetrapeptide.
AB  - Potent monomeric and dimeric cyclic peptide very late antigen-4 (VLA-4)
      inhibitors have been designed based on a tetrapeptide (Ile-Leu-Asp-Val) sequence
      present in a 25-amino acid peptide (CS-1) reported in the literature. The
      peptides, synthesized by the SPPS techniques, were evaluated in the in vitro cell
      adhesion assays and in the in vivo inflammation models. The N- to C-terminal
      cyclic peptides such as cyclo(Ile-Leu-Asp-Val-NH-(CH2)2-S-(CH2)2-CO) (28) and
      cyclo(MeIle-Leu-Asp-Val-D-Ala-D-Ala) (31), monomeric and dimeric peptides
      containing piperazine (Pip) or homopiperazine (hPip) residues as linking groups,
      e.g. cyclo(MeIle-Leu-Asp-Val-Pip-CH2CO-NH-(CH2)2-S-CH2-CO) (49) and cyclo(MeIle
      Leu-Asp-Val hPip-CH2CO-MeIle-Leu-Asp-Val-hPip-CH2CO) (58) and cyclic peptides
      containing an amide bond between the side chain amino group of an amino acid such
      as Lys and the C-terminal Val carboxyl group, e.g. Ac-cyclo(D-Lys-D-Ile-Leu-Asp
      Val) (62) and beta-Ala-cyclo(D-Lys-D-Leu-Leu-Asp-Val) (68) were more potent than
      CS-1 in inhibiting the adhesion of the VLA-4-expressing MOLT-4 cells to
      fibronectin. The more potent compounds were highly selective and did not affect
      U937 cell adhesion to fibronectin (VLA-5), PMA-differentiated U937 cell adhesion
      to intercellular cell adhesion molecule- 1-expressing Chinese hamster ovary cells
      (LFA-1) and ADP-induced platelet aggregation (GPIIb/IIIa). A number of the more
      potent compounds inhibited ovalbumin-induced delayed type hypersensitivity in
      mice and some were 100-300 times more potent (ED50 = 0.003-0.009 mg/kg/day, s.c.)
      than CS-1. Two peptides, Ac-cyclo(D-Lys D-Ile-Leu-Asp-Val) (62) and cyclo(CH2CO
      Ile-Leu-Asp-Val-Pip-CH2CO-Ile-Leu-Asp-Val-Pip) (55), were formulated in poly(DL
      lactide-co-glycolide) depots and the release profile was investigated in vitro
      over a 30-day period.

PMID- 10946998
TI  - Fluorescein-ERG, a sensitive method for the detection of vascular damage in
      diabetic patients.
AB  - The purpose of this paper was to provide evidence for the reintroduction of
      simultaneously performed fluorescein angiography and electroretinography in the
      detection of diabetic retinopathy. ERG observations were made in conjunction with
      fluorescein angiography of 13 patients suffering from type I diabetes mellitus
      for five to 13 years. Only patients without any fluorescein leakage during
      angiography and without any morphologic changes in the fundus were involved in
      the study. Gold foil electrodes were used for recording. A stroboscopic lamp
      provided flashing light stimulation through a monochromatic blue filter.
      Intravenous fluorescein administration caused an immediate reduction in the ERG
      response. This reduction was seen both in the control subjects and in diabetes
      patients. In the control group, the reduction was over in 30-45 min, while in the
      diabetes group a considerable amplitude elevation was seen in all recordings
      between 15 and 60 min post-fluorescein. In the adaptation control group, where
      only repeated ERG recordings were employed every 15 min, a slight decrease in the
      a wave and a slight elevation of the b wave were observed during the whole
      recording period. No complaints or side-effects were detected during the
      observations. As all the patients displayed a normal fluorescein angiography
      besides elevated b wave after fluorescein administration, and this elevation was
      seen exclusively in the diabetic group, our study raises the possibility that
      this diagnostic method can be used in the detection of diabetic retinopathy.

PMID- 10946999
TI  - Alterations of the retino-cortical conduction in patients affected by classical
      congenital muscular dystrophy (CI-CMD) with merosin deficiency.
AB  - Immunocytochemical analysis of the laminin alpha-2 (merosin) chain in the muscle
      of patients with Classic Congenital Muscular Dystrophy (Cl-CMD) differentiates
      the types of the disease associated with a merosin deficit from those that are
      merosin positive. Patients with Central Nervous System involvement in merosin
      negative Cl-CMD always present alterations of the white matter at RMI, but
      usually these are not clinically significant. While ocular malformations
      (microphthalmia, alterations of the anterior chamber, of the retina, or of the
      angle and cataract) and damage to the Central Nervous System are described in
      some subtypes of CMD (Muscle Eye Brain disease, Walker Warburg Syndrome), ocular
      involvement and retino-cortical conduction in merosin negative Cl-CMD are not
      well known. This study reports on four patients affected by merosin negative Cl
      CMD. All these patients presented important alterations of the white matter
      associated with ventricular enlargement and, in one case, with pachygyria and
      micropolygyria. Refraction, visual acuity, ocular motility, anterior segment and
      fundus were examined. ERG Maximal, Cone and Rod response, VEP transient pattern
      reversal was carried out as well. Significant alterations at the standard
      ophthalmologic examination or of the electroretinogram responses were not
      registered while, in all cases, important modifications in retino cortical
      conduction (reduction in amplitude, increase in latency, reduction in amplitude
      on the lateral derivations) were observed, demonstrating involvement of the optic
      pathway at different levels during the course of this disease.

PMID- 10947000
TI  - Mechanism of binocular interaction in refraction errors: study using pattern
      reversal visual evoked potentials.
AB  - In this study we sought to determine whether a natural condition involving fine
      discrimination, for example moderately severe myopia, might yield interesting
      information regarding the binocular interaction expressed by visual evoked
      potentials (VEPs). We studied ten normal subjects with a mild refraction
      deficits. Transient VEPs were elicited by monocular and binocular stimulation
      under conditions of natural and lens-corrected vision. The visual stimulus was a
      pattern-reversal checkerboard consisting of 15' and 40' checks. VEPs in response
      to binocular stimulation were compared with monocular VEPs. We plotted the
      monocular 'better-VEP' and 'worse-VEP' response, since significant differences
      between individual eye stimulations were present. We found no significant
      difference between the mean N75 and P100 latencies of the binocular VEP and the
      better monocular VEP, regardless of the check size used and of natural or
      corrected vision. Under all stimulus conditions, the mean amplitude of the N75
      P100 of the binocular VEPs was also larger than the better monocular VEP
      response. The difference proved more significant when we stimulated our subjects
      with smaller squares and left vision uncorrected. The mean P100-N145 amplitude
      obtained with binocular stimulation was larger than the better monocular VEP
      response only when using small checks (15') and uncorrected vision. Overlapping
      latencies are consistent with an earlier hypothesis that monocular and binocular
      VEPs originate postsynaptically from the binocular neurons in the primary visual
      cortex. The gain in amplitude achieved by binocular stimulation may depend upon
      the removal of 'tonic interocular inhibition' and/or on a cortical modulatory
      mechanism.

PMID- 10947002
TI  - Retinitis pigmentosa in association with acromegaly: a case report.
AB  - Retinal abnormalities, unrelated to visual pathway compression, in acromegalic
      patients were originally described by Small in 1972 (Smail JM. Primary pigmentary
      degeneration of the retina and acromegaly in a case of pituitary adenoma. Br J
      Ophthalmol 1972; 56: 25-31). He illustrated a case of primary pigmentary
      degeneration of the retina occurring in a patient with a chromophobe adenoma of
      the pituitary gland. To the best of our knowledge this remains the sole,
      published case of this association. We report on two male patients, with an
      acromegalic appearance, one caused by a pituitary adenoma, the other associated
      with a Rathke's cleft cyst, presenting to our department of ophthalmology with
      the clinical picture of pigmentary degeneration of the retina.

PMID- 10947001
TI  - Mutations of the XLRS1 gene cause abnormalities of photoreceptor as well as inner
      retinal responses of the ERG.
AB  - Intensity-series rod and cone ERGs were recorded in 19 patients with XLRS and 26
      control eyes. All patients were examined by one ophthalmologist and diagnosed on
      the basis of fundus appearance and evidence of the disease in other males in the
      same family. Mutations in the XLRS1 gene have been identified in 15 of the
      patients. Dark-adapted ERGs were significantly different from controls for all
      test conditions and for both a-wave and b-wave responses. Abnormalities were
      detectable in all patients but there was considerable variation in the severity
      of abnormality. One third of the patients had the dark-adapted 'negative-wave'
      response typically associated with inner retinal disorder, but about one third
      showed only mild depression of the b-wave while the remainder had abnormally low
      a-waves in addition to depressed b-waves. Light-adapted responses were also
      affected and both a-wave and b-wave responses differed significantly from
      controls, but the 'negative-wave' response was not seen in any patient. The
      severity of the ERG abnormality did not correlate with the classification of
      fundus appearance or patient age suggesting that retinal function is relatively
      stable throughout life. The severity of ERG abnormalities did not correlate with
      the type of mutation and responses could differ between affected males within the
      same family. These results indicate considerable heterogeneity of ERG response
      without clinical, age or genetic correlate. The abnormal a-wave responses
      indicate that photoreceptor as well as inner retinal layer function may be
      affected in XLRS, at least in some patients.

PMID- 10947003
TI  - Multifocal pattern VEP perimetry: analysis of sectoral waveforms.
AB  - PURPOSE: The objective detection of local visual field defects using multi-focal
      pattern visual evoked potentials (VEP) has recently been described. The
      individual waveforms show variable polarity in different parts of the visual
      field due to underlying cortical convolutions. Normal trace arrays were examined
      to determine if certain areas of similar waveform could be grouped for analysis,
      while minimising cancellation of data. METHOD: The VEP was assessed using multi
      focal pseudo-randomly alternated pattern stimuli which were cortically scaled in
      size. Bipolar occipital electrodes were used for recording. Waveforms were
      compared for different locations within the field up to 25 degrees of
      eccentricity. Analysis of sectors showing similarly shaped waveforms was
      performed. Twelve normal subjects were studied. RESULT: Grouping waveforms by
      sectors of similar waveform increased the total calculated upper hemifield
      amplitude by 60%, compared with simple summations of responses for the whole
      hemifield. The inferior hemifield showed more consistent waveforms throughout,
      with the amplitude only increasing by 11% with sectoral summation. Intra-subject
      variability (10.6%) is less for sectors than for individual points (17.3%). Inter
      subject amplitude differences are high, calculated at 56% for individual points
      and 45% for sectors. CONCLUSIONS: Due to differences in waveform as a result of
      underlying cortical anatomy, individual VEP responses from multifocal recordings
      should be grouped as sectors along the vertical meridian and above and below the
      horizontal, rather than by hemifields or quadrants. This finding is significant
      if one is considering within-field grouping strategies similar to the glaucoma
      hemifield test used in conventional perimetry, or reporting derived overall VEP
      amplitudes and latencies from a multifocal recording. Large amplitude variations
      between individuals and small signals from horizontal and upper field seen in
      single channel recording, still limit the application of this technique as a form
      of objective perimetry.

PMID- 10947004
TI  - Recording the photopic electroretinogram from conscious adult Yucatan micropigs.
AB  - The micropig is viewed by many as one of the best animal models of human system
      physiology. The purpose of this study was to develop a simple, rapid and reliable
      method to record clinical electroretinograms from conscious adult Yucatan
      micropigs. Photopic ERGs were recorded from 18 conscious animals following a 3-h
      period of preadaptation to a moderate photopic environment. Rectal temperature
      and blood pressure were monitored throughout the experiment. In order to test the
      reproducibility of our procedure, the same protocol was repeated (n=6 micropigs)
      on three different recording sessions each separated by a 48-h period. Our
      results indicate that the recording of reproducible ERGs, in the conscious
      Yucatan micropig, is feasible provided that an adequate experimental approach is
      used. We believe that our method will enable investigators to perform retinal
      physiology experiments using an approach which is compatible with that used in a
      human clinical setup thus facilitating the transposition of experimental data
      from animal to human.

PMID- 10947005
TI  - A VEP investigation of parallel visual pathway development in primary school age
      children.
AB  - Different features of visual function mature along unique timescales through
      infancy and early childhood. It is not clear which functions continue to mature
      in school age children. Functions believed to be mediated by the Magnocellular
      (M) and Parvocellular (P) pathways were compared in five- (n=25), eight- (n=21)
      and eleven-year-old children (n=21) and young adult controls (n=20). Steady-state
      visual evoked potentials were recorded from occipital electrodes in response to
      very low spatial frequency gratings, at a series of contrasts (M), and to high
      contrast gratings at a series of spatial frequencies (P). No evidence was found
      to indicate M pathway development across these age groups. However, the youngest
      children demonstrated elevated VEP thresholds to the high contrast gratings
      compared with either the adults or eleven-year-olds. This difference in threshold
      implies an immaturity of the high contrast, high spatial frequency stream, i.e.
      the putative P pathway.

PMID- 10947006
TI  - Impaired saccadic eye movement in diabetic patients: the relationship with visual
      pathways function.
AB  - The aim of this study was to evaluate whether a correlation existed between
      saccadic eye movements and visual pathways function in diabetic patients.
      Saccadic or fast Eye Movement System (EMS) and Visual Evoked Potentials (VEPs)
      were assessed in 20 insulin-dependent diabetic mellitus (IDDM) patients without
      long-term complications and in stable metabolic control and in 21 age-matched
      control subjects. In IDDM patients we observed significantly (p<0.01) longer EMS
      latency, while EMS velocity and accuracy were similar to those of controls; VEPs
      showed a significant delay in N75, P100, N145 latencies and significant reduction
      of N75-P100 and P100-N145 amplitudes. In IDDM patients no relationships between
      EMS and VEP parameters were found. In conclusion, EMS latency delay suggests an
      impairment of the saccadic eye movement system, while impaired VEPs may be
      ascribed to a dysfunction of the visual pathways. The lack of correlation between
      VEPs impairment and EMS latency delay suggests that in our IDDM patients the
      delay of saccadic latency cannot be exclusively related to a visual pathways
      dysfunction and could be ascribed to a diffuse neuronal involvement.

PMID- 10947007
TI  - The neonatal development of the light flash visual evoked potential.
AB  - AIMS: To follow visual development longitudinally in the normal neonate using the
      flash visual evoked potential (VEP) and to find indications for a relationship
      between potential development and visual development. METHODS: Twenty healthy
      infants, born at term, were included in the study. Flash and patterned flash VEPs
      were used. The first VEP was recorded the day of birth or just postnatally, and
      succeeding recordings were performed the following weeks and months. RESULTS: The
      data revealed different types of VEP in the neonatal period suggesting great
      variability in visual function on the day of birth. In the early development a
      potential of long latency and duration preceded the development of a more
      compound potential of shorter latency. The two types of responses seemed to
      coalesce during early development; the first late response was attenuated and was
      eventually integrated in the more mature VEP. At approximately five weeks of age
      changes in the VEP were simultaneous with the development of responsive smiling
      and another visual behaviour of the infants. CONCLUSIONS: The results showed many
      similarities between the VEP development in infants and in immature animals. In
      developing animals geniculo-cortical and extra-geniculate visual afferent
      pathways evoke two types of VEPs similar to those recorded in the present study.
      The early responses were also similar to previous recordings from children with
      lesions in the geniculo-striatal pathway or primary cortex. Our interpretation of
      the results was that the human VEP also consists of responses evoked by afferents
      running both in geniculo-cortical and extra-geniculate pathways and that the two
      types of responses could be separated in the VEP in the neonatal period. These
      findings are important for our understanding of conditions with a delay in visual
      maturation, for example intracranial haemorrhages, hydrocephalus, pre/dys
      maturity and 'idiopathic' delayed visual maturation.

PMID- 10947008
TI  - Effects of refractive blur on the multifocal electroretinogram.
AB  - A significant difference in the response density of the MF-ERG response has been
      suggested for every 2 diopter change of refraction. The influence of refractive
      blur on the MF-ERG was studied in 8 healthy volunteers using either the VERISTM
      system (Group A: n=5) or Retiscan(TM) (Group B: n=3). For each eye recordings
      were obtained with a corrective lens of -3 dpt, 0 dpt, +3 dpt and +6 dpt placed
      in front of the contact lens electrode. The viewing distance was adjusted to
      compensate for the induced changes in the retinal image size. When the changes in
      retinal image size due to the refractive lens were compensated for, no influence
      due to refraction was observed in either latencies or amplitudes of (KI (P >
      0.05). This held true for the central response average (four degrees) as well as
      for the outer 6-25 degrees. In KII.1 only the peripheral amplitudes of Group B
      showed an influence due to refraction (P < or = 0.05). This may be due to
      adaptation as the recordings of group B were obtained in succession. As expected,
      significant differences were observed when the recordings obtained with the
      different systems were compared (P < or = 0.05).

PMID- 10947009
TI  - The effect of long-term use of benzodiazepines on the eye and retina.
AB  - Thirty patients on long-term benzodiazepine medication were subjected to full
      ophthalmoscopic examination. Of these 19 (63.3%) complained of symptoms of
      irritation, blurred vision or difficulty in reading. None, however, had reduced
      visual acuities apart from two where the cause was longstanding amblyopia.
      Thirteen patients had some form of retinal finding, 9 macular and 4 non-macular.
      Of the 14 who presented for flash and pattern electroretinography (ERG), none
      showed any abnormality which could be ascribed to the medication, its total dose,
      or duration. We conclude, on the basis of the evidence from this small cohort,
      that long-term benzodiazepine medication has little effect upon retinal function
      as signalled by the ERG.

PMID- 10947010
TI  - Do's and don'ts in Fourier analysis of steady-state potentials.
AB  - Fourier analysis is a powerful tool in signal analysis that can be very
      fruitfully applied to steady-state evoked potentials (flicker ERG, pattern ERG,
      VEP, etc.). However, there are some inherent assumptions in the underlying
      discrete Fourier transform (DFT) that are not necessarily fulfilled in typical
      electrophysiological recording and analysis conditions. Furthermore, engineering
      software-packages may be ill-suited and/or may not fully exploit the information
      of steady-state recordings. Specifically: * In the case of steady-state
      stimulation we know more about the stimulus than in standard textbook situations
      (exact frequency, phase stability), so 'windowing' and calculation of the
      'periodogram' are not necessary. * It is mandatory to choose an integer
      relationship between sampling rate and frame rate when employing a raster-based
      CRT stimulator. * The analysis interval must comprise an exact integer number
      (e.g., 10) of stimulus periods. * The choice of the number of stimulus periods
      per analysis interval needs a wise compromise: A high number increases the
      frequency resolution, but makes artifact removal difficult; a low number 'spills'
      noise into the response frequency. * There is no need to feel tied to a power-of
      two number of data points as required by standard FFT, 'resampling' is an easy
      and efficient alternative. * Proper estimates of noise-corrected Fourier
      magnitude and statistical significance can be calculated that take into account
      the non-linear superposition of signal and noise. These aspects are developed in
      an intuitive approach with examples using both simulations and recordings. Proper
      use of Fourier analysis of our electrophysiological records will reduce recording
      time and/or increase the reliability of physiologic or pathologic
      interpretations.

PMID- 10947011
TI  - The influence of visual input on the vestibulo-ocular reflex.
AB  - In order to stabilise a fixation target on the retina, eye movements have to
      compensate for head movements. During slow head movements visual feedback can
      control these eye movements. During fast movements of the head, mainly the
      vestibulo-ocular reflex (VOR) controls eye movements, as visual feedback is too
      slow. However, visual feedback is an important factor in controlling the VOR;
      e.g. the gain of the VOR depends on the distance of the target. This study
      investigates the influence of retinal image position during fast head movements.
      The experiments were carried out in five human subjects using scleral search
      coils. The adaptation of each eye individually to a change of retinal position of
      a target was examined during head shaking. The change in visual input was carried
      out by placing Fresnel prisms of different strengths in front of both eyes, thus
      inducing a change in retinal image position without changing the retinal slip.
      The results show, that both eyes make the appropriate corrections when the visual
      input changes, even during fast head-movements. These corrections did not
      influence the gain of the VOR. From these results we conclude, that retinal image
      position besides retinal slip has a major influence on the monocular eye
      movements even at high head rotation frequencies.

PMID- 10947012
TI  - Accommodative facility training with a long term follow up in a sample of school
      aged children showing accommodative dysfunction.
AB  - The primary aim of this project was to study the effect of flip lens-training on
      the accommodative function in a group of children with accommodative dysfunction
      and subjective symptoms such as asthenopia, headache, blurred vision, and
      avoidance of near activity. We also wanted to measure the accommodative facility
      among the children in comparison with a control group. Another aim of the study
      was whether flip lens-training increased accommodative facility, and to find out
      if it also had a positive effect on their asthenopia and related problems also in
      long term. Following the training period the accommodative facility and
      accommodative function significantly increased and two years after finishing the
      training period no child had regained any subjective symptoms and the objective
      findings were almost the same as at the end of facility training period. These
      results suggest that accommodative facility training is an efficient method built
      on loss of symptoms among children with accommodative infacility.

PMID- 10947013
TI  - A perspective on sentinel lymph node biopsy in colorectal cancer: the race
      between surgical technology and molecular oncology.

PMID- 10947014
TI  - Values in leadership--lessons learned from patients, students, and colleagues.

PMID- 10947015
TI  - Cost and utilization impact of a clinical pathway for patients undergoing
      pancreaticoduodenectomy.
AB  - BACKGROUND: When implemented in several common surgical procedures, clinical
      pathways have been reported to reduce costs and resource utilization, while
      maintaining or improving patient care. However, there is little data to support
      their use in more complex surgery. The objective of this study was to determine
      the effects of clinical pathway implementation in patients undergoing elective
      pancreaticoduodenectomy (PD) on cost and resource utilization. METHODS: Outcome
      data from before and after the development of a clinical pathway were analyzed.
      The clinical pathway standardized the preoperative outpatient care, critical
      care, and postoperative floor care of patients who underwent PD. An independent
      department determined total costs for each patient, which included all hospital
      and physician costs, in a blinded review. Outcomes that were examined included
      perioperative mortality, postoperative morbidity, length of stay, readmissions,
      and postoperative clinic visits. RESULTS: From January, 1996 to December, 1998,
      148 consecutive patients underwent PD or total pancreatectomy; 68 before pathway
      development (PrePath) and 80 after pathway implementation (PostPath). There were
      no significant differences in patient demographics, comorbid conditions,
      underlying diagnosis, or use of neoadjuvant therapy between the two groups. Mean
      total costs were significantly reduced in PostPath patients compared with PrePath
      patients ($36,627 vs. $47,515; P = .003). Similarly, mean length of hospital stay
      was also significantly reduced in PostPath patients (13.5 vs. 16.4 days; P =
      .001). The total cost differences could not be attributed solely to differences
      in room and board costs. Cost and length-of-stay differences remained when
      outliers were excluded from the analysis. Despite these findings, there were no
      significant differences between PrePath and PostPath patients in terms of
      perioperative mortality (3% vs. 1%), readmissions within 1 month of discharge
      (15% vs. 11%), or mean number of clinic visits within 90 days of discharge (3.3
      vs. 3.4 visits). CONCLUSIONS: The establishment of a clinical pathway for PD
      patients dramatically reduced costs and resource utilization without any apparent
      detrimental effect on quality of patient care. These findings support the
      implementation of clinical pathways for PD patients, as well as investigation
      into pathway care for other complex surgical procedures.

PMID- 10947016
TI  - Surgery after downstaging of unresectable hepatic tumors with intra-arterial
      chemotherapy.
AB  - BACKGROUND: This retrospective study was performed to assess the outcome among
      patients who underwent hepatic resection or tumor ablation after hepatic artery
      infusion (HAI) therapy down-staged previously unresectable hepatocellular
      carcinoma (HCC) or liver metastases from colorectal cancer (CRC). METHODS:
      Between 1983 and 1998, 25 patients with HCC and 383 patients with hepatic CRC
      metastases were treated with HAI therapy for unresectable liver disease. We
      retrospectively reviewed the records of 26 (6%) of these patients who underwent
      subsequent surgical exploration for tumor resection or ablation. RESULTS: At a
      median of 9 months (range 7-12 months) after HAI treatment, four patients (16%)
      with HCC underwent exploratory surgery; two underwent resection with negative
      margins, and the other two were given radiofrequency ablation (RFA) because of
      underlying cirrhosis. At a median postoperative follow-up of 16 months (range 6
      48 months), all four patients were alive with no evidence of disease. At a median
      of 14.5 months (range 8-24 months) after HAI therapy, 22 patients with hepatic
      CRC metastases underwent exploratory surgery; 10 underwent resection, 6 underwent
      resection and RFA or cryotherapy, and 2 underwent RFA only. At a median follow-up
      of 17 months, 15 (83%) of the 18 patients with CRC who had received surgical
      treatment had developed recurrent disease; the other 3 died of other causes (1 of
      postoperative complications) within 7 months of the surgery. One patient in whom
      disease recurred underwent a second resection and was disease-free at 1 year
      follow-up. CONCLUSIONS: Hepatic resection or ablation after tumor downstaging
      with HAI therapy is a viable option for patients with unresectable HCC. However,
      given the high rate of recurrence of metastases from CRC, hepatic resection or
      ablation after downstaging with HAI should be used with caution.

PMID- 10947017
TI  - A prospective analysis of the cephalic vein cutdown approach for chronic
      indwelling central venous access in 100 consecutive cancer patients.
AB  - BACKGROUND: Chronic indwelling central venous access devices (CICVAD) generally
      are placed by the percutaneous subclavian vein approach. The cephalic vein
      cutdown approach is used only infrequently. Although the technique has been well
      described, few prospective data are available on the cephalic vein cutdown
      approach. METHODS: From September 9, 1998, to July 20, 1999, the cephalic vein
      cutdown approach was attempted in 100 consecutive cancer patients taken to the
      operating room with the intention of placing CICVAD. Median patient age was 54.5
      years (range 18-88), with 46 men and 54 women. Twenty-five patients had
      gastrointestinal malignancies, 17 had breast cancer, 15 had lymphoma, 13 had lung
      cancer, 12 had leukemia, 5 had multiple myeloma, and 13 had other malignancies.
      Patients were followed prospectively for immediate and long-term outcome.
      RESULTS: CICVAD placement via the cephalic vein cutdown approach was successful
      in 82 patients; the remaining 18 patients required conversion to a percutaneous
      subclavian vein approach. The reasons for inability to place CICVAD via cephalic
      vein cutdown approach were a cephalic vein that was too small (10 patients), an
      absent cephalic vein (7 patients), and inability to traverse the angle of
      insertion of the cephalic vein into the subclavian vein (1 patient). There were
      56 subcutaneous ports and 26 tunneled catheters. Median operating time was 44
      minutes (range, 26-79 minutes). No postoperative pneumothorax occurred. Median
      catheter duration was 198 days (range, 0-513 days). Long-term complications
      included catheter-related bacteremia (6%), site infection (2%), deep venous
      thrombosis (5%), port pocket hematoma (1%), and superior vena cava stricture
      (1%). Thirty-seven percent of patients have died since CICVAD placement. Twenty
      nine percent of the CICVADs have been removed. CONCLUSIONS: The cephalic vein
      cutdown approach was successful in 82% of patients. This approach is a safe and
      useful alternative to the percutaneous subclavian vein approach.

PMID- 10947018
TI  - Most important lymph node information in gastric cancer: multivariate prognostic
      study.
AB  - BACKGROUND: In gastric cancer, the level and number of lymph node metastases is
      useful for predicting survival, and there are several staging systems for lymph
      node metastasis. The aim of this study was to compare the several lymph node
      classifications and to clarify the most important lymph node information
      associated with prognosis using multivariate analysis. METHODS: A total of 106
      patients with histologically node-positive gastric cancer treated by radical
      gastrectomy and extended lymph node dissection (D2, D3) were studied. The level
      of lymph node metastasis was categorized simply as Level I nodes (perigastric,
      No.1-6), Level II nodes (intermediate, No.7-9), and Level III nodes (distant,
      No.10-16), irrespective of the tumor location. The Level II nodes included lymph
      nodes along the left gastric artery, common hepatic artery, and celiac trunk.
      RESULTS: Overall 5-year survival rate was 51%. Univariate analysis showed that 5
      year survival rate was significantly influenced by the level of positive nodes (P
      < .01), total number of positive nodes (P < .01), number of positive Level I
      nodes (P < .01), and number of positive Level II nodes (P < .01), in addition to
      the tumor location (P < .05), tumor size (P < .05), gross type (P < .01), and
      depth of wall invasion (P < .01). Of these, independent prognostic factors
      associated with 5-year survival rate were the number of positive Level II nodes
      (0-1 vs. > or =2) (62% vs. 19%, P < .01) and the depth of wall invasion (within
      vs. beyond muscularis) (79% vs. 43%, P < .01). CONCLUSIONS: Among several staging
      systems for lymph node metastases, the number of positive Level II nodes provided
      the most powerful prognostic information in patients with node-positive gastric
      cancer. When there were two or more metastases in the Level II nodes, prognosis
      was poor even after D2 or D3 gastrectomy.

PMID- 10947019
TI  - Expression and prognostic significance of pepsinogen C in gastric carcinoma.
AB  - BACKGROUND: In this study we evaluated the expression and clinical significance
      of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in
      the stomach, in patients with gastric cancer. METHODS: Pepsinogen C expression
      was examined by immunohistochemical methods in a series of 95 gastric carcinomas.
      The prognostic value of pepsinogen C was retrospectively evaluated by
      multivariate analysis taking into account conventional prognostic parameters.
      Follow-up period of patients was 21.4 months. RESULTS: A total of 25 (26.3%)
      gastric carcinomas stained positively for pepsinogen C. The percentage of
      pepsinogen C-positive tumors was higher in well-differentiated (50%) than in
      moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P <
      .05). Similarly, significant differences in pepsinogen C immunostaining were
      found between node-negative and node-positive tumors (47.1% vs. 14.7%; P < .001).
      In addition, statistical analysis revealed that pepsinogen C expression was
      associated with clinical outcome in gastric cancer patients. Low pepsinogen C
      levels predicted short overall survival periods in the overall group of patients
      with gastric cancer (P < .001), and in 71 patients with resectable carcinomas (P
      < .005). Multivariate analysis according to Cox's model indicated that pepsinogen
      C immunostaining was an independent predictor of outcome for both overall and
      resectable gastric cancer patients (P < .05, for both). CONCLUSIONS: The
      expression of pepsinogen C in gastric cancer may represent a useful biological
      marker able to identify subgroups of patients with different clinical outcomes.

PMID- 10947020
TI  - Clinicopathological characteristics of gastric carcinoma in young and elderly
      patients: a comparative study.
AB  - BACKGROUND: Gastric cancer is one of the most common gastrointestinal
      malignancies world-wide. Some studies have suggested that it has a worse
      prognosis in young than in elderly patients. METHODS: All young and elderly
      patients treated for gastric adenocarcinoma during the period 1988 to 1994 in a
      tertiary referral center in Mexico City were included. Demographic, clinical, and
      pathologic features of young patients (less than 40 years of age) with gastric
      cancer were compared with those of elderly patients (70 years of age or older)
      with the same diagnosis. Overall survival was the main outcome measure. RESULTS:
      There were 38 patients in each group. The mean age of the young and elderly
      groups was 33 and 77 years, respectively. Family history of gastric cancer was
      reported by 6 patients of the younger group and by 1 patient in the older group
      (P < .05). Most patients in both groups were symptomatic and had an advanced
      stage of the disease. With a mean follow-up of 17 months, the overall median
      survival for all patients was 12 months. By group, the median survival was 13 and
      12 months for the young and elderly patients, respectively (P = .38). Variables
      with significant impact on survival were the stage of the disease, possibility of
      surgical resection, location of the tumor, and a family history of gastric
      cancer. CONCLUSIONS: Young patients represent a significant proportion of
      patients with gastric cancer in Hispanic populations. There were no significant
      differences in clinicopathological characteristics and outcome of gastric
      adenocarcinoma between young and elderly patients. Survival was determined by the
      stage of the tumor and the possibility of complete surgical resection.

PMID- 10947021
TI  - Proximal versus distal gastric carcinoma--what are the differences?
AB  - BACKGROUND: The incidence of proximal gastric third carcinoma (PGC) has been
      rising in recent years. Classification and surgical therapy remain controversial.
      METHODS: Between May 1986 and October 1997, 532 patients were operated for
      primary gastric carcinoma. All patient data were analyzed retrospectively
      comparing findings in patients with PGC and those with distal gastric carcinoma
      (DGC). RESULTS: Two hundred fifty patients had a PGC, and 282 patients had a DGC.
      The rate of RO resections was 79.3% for PGC and 81.6% for DGC. In 93.9% of the
      patients with PGC total gastrectomy was performed; for DGC total gastrectomy was
      done in 74.5% of patients. Postoperative morbidity and mortality were 29.2% for
      PGC and 23.8% for DGC, and 3.2% for PGC and 3.5% for DGC, respectively. Patients
      with advanced tumor stages (stage III and IV) were more common in the PGC group
      (73.3% vs. 53.6% in DGC). After RO resection, the 5-year survival rate was 33.2%
      for PGC and 59.7% for DGC. CONCLUSIONS: There was no significant difference
      between the rates of RO resections for PGC and DGC. Total gastrectomy can be
      performed with low postoperative morbidity and mortality. PGC and DGC represent
      the same tumor entity, and prognosis is similar, but due to more advanced tumor
      stages, the long-term survival is worse for patients with PGC than for those with
      DGC. Left retroperitoneal lymphadenectomy may be indicated for PGC.

PMID- 10947022
TI  - Distant soft tissue metastases: a series of 30 new patients and 91 cases from the
      literature.
AB  - BACKGROUND: Thirty patients with soft-tissue metastases were reviewed
      retrospectively and compared with 91 cases previously reported. Soft tissue
      metastases were most commonly presented to the musculoskeletal oncologist as a
      painful mass in patients with no history of cancer. In this setting, lung
      carcinoma was the most frequent primary source. The purpose of this article is to
      report the largest single series of distant soft-tissue metastases and to compare
      the findings with those of the literature. METHODS: Thirty consecutive patients
      were referred to musculoskeletal oncologists. Their cases were reviewed
      retrospectively for comparison with 91 cases from the clinical literature.
      RESULTS: The most common clinical presentation of the soft-tissue mass was as the
      presenting symptom of previously undiagnosed cancer or concurrent with the
      primary source of cancer. A minority of cases were discovered in the setting of
      widespread metastases. Twenty-one new patients had carcinomas, 6 sarcomas, and 1
      each multiple myeloma, lymphoma, and melanoma. Lung carcinoma was the most common
      primary source. The most common presenting symptom was that of a painful mass.
      Skeletal muscle of the thigh was the most common site. Radiological features were
      not specific. Soft tissue sarcoma was a common clinical misdiagnosis. Twenty-one
      new patients were dead of disease at a mean 5.4 months (range 1-19 months) after
      diagnosis of the metastasis: this percentage was similar to that reported in the
      literature. CONCLUSIONS: In this musculoskeletal oncology referral-based clinical
      series, soft tissue metastases most commonly occur in patients with a painful
      soft tissue mass and no history of cancer. Lung is the most frequent primary
      source. Treatment should be individualized according to the underlying disease
      and its prognosis.

PMID- 10947023
TI  - Clinico-pathological data and prognostic factors in completely resected AJCC
      stage I-III liposarcomas.
AB  - BACKGROUND: In general, although biological behavior and prognosis of
      liposarcomas (LPS) are more favorable compared with most other soft tissue
      sarcomas (STS), prognosis can vary widely depending on tumor characteristics,
      especially histological subtype and tumor grade. PATIENTS AND METHODS: All
      consecutive, completely resected stage I-III LPS (as determined by the American
      Joint Committee on Cancer staging guidelines), treated at the Groningen
      University Hospital from 1977-2000, were analyzed. RESULTS: A total of 69
      patients, 35 males and 34 females, median age 51 (range 11-80) years, were
      reviewed. After a median follow-up of 71 (range 5-231) months, the overall local
      recurrence and metastasis rate at five years after diagnosis were 27% and 16%,
      respectively. Retroperitoneal localization was a significant negative prognostic
      factor regarding local recurrence; dedifferentiation, grade II-III, and deep
      location regarding distant metastasis; and dedifferentiation, grade II-III, stage
      II-III, size >20 cm and non-radical resection regarding survival. CONCLUSIONS:
      LPS have a relatively mild biologic behavior, with the exception of very large,
      deeply located, dedifferentiated and/or grade II-III LPS. Radical resection is
      important for disease-specific survival. LPS have a relatively mild biologic
      behavior, with the exception of very large, deeply located, dedifferentiated
      and/or grade II-III LPS.

PMID- 10947024
TI  - Role of specimen radiography in patients treated with skin-sparing mastectomy for
      ductal carcinoma in situ of the breast.
AB  - BACKGROUND: Specimen radiography is an important part of breast conservation
      surgery for ductal carcinoma in situ (DCIS). The objective of this study was to
      determine whether mastectomy specimen radiography could help in obtaining
      negative resection margins in patients with DCIS undergoing skin-sparing
      mastectomy (SSM) with immediate breast reconstruction (IBR). METHODS: Of 95
      patients treated at our institution with SSM and IBR for DCIS, 35 had specimen
      radiography. The mastectomy specimen was first examined grossly and then inked,
      serially sectioned, and sent for radiographic assessment. Tissue slices
      containing calcifications were identified for pathologic evaluation. Additional
      tissue was excised if tumor was found near the inked margins or if calcifications
      were found near the radiographic margins. RESULTS: Of the 35 patients who had
      specimen radiography, the radiographic margins were free of calcifications in 30
      patients (86%); of these patients, the margins on the final histologic
      examination were free of tumor in 27 and within 1 mm in 3. The other five
      patients (14%) had calcifications close to the radiographic margin; four
      underwent an intraoperative re-excision, but the margin for one of those four
      patients was still positive on final histologic examination. Margins were found
      to be negative by both mastectomy specimen radiography and histology in 77% of
      the patients. Of the 95 patients with DCIS, three patients (3%), none of whom had
      specimen radiography, developed local recurrences. One of these was successfully
      re-treated, one died as a result of synchronous distant metastases, and one was
      lost to follow-up. At a median follow-up time of 3.7 years, 93 patients (98%)
      were alive and free of disease. CONCLUSIONS: Intraoperative radiography of
      mastectomy specimens may be useful for assessing margin status and for
      identifying the location of microcalcifications within tissue slices.

PMID- 10947025
TI  - Combined bupropion-levodopa-trazodone therapy of sleep-related eating and sleep
      disruption in two adults with chemical dependency.

PMID- 10947026
TI  - Transverse myelitis associated with restless legs syndrome and periodic movements
      of sleep responsive to an oral dopaminergic agent but not to intrathecal
      baclofen.
AB  - Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are
      related sleep disorders that occur with increased frequency in spinal cord
      disease. Effective treatment may be obtained with dopaminergic or opioid drugs,
      while anticonvulsants, benzodiazepines, and possibly baclofen may be helpful.
      This report describes a patient who developed RLS and PLMD after acute transverse
      myelitis associated with infectious mononucleosis, and failed to respond to
      intrathecal baclofen. All symptoms of RLS/PLMD resolved after treatment with
      pergolide.

PMID- 10947027
TI  - Clinical characteristics and frequency of the hereditary restless legs syndrome
      in a population of 300 patients.
AB  - There is a genetic contribution to the idiopathic restless legs syndrome (iRLS).
      An autosomal dominant mode of inheritance is suspected, but as yet no gene has
      been identified. To assess the frequency and characteristics of the hereditary
      restless legs syndrome (RLS) in comparison to those of non-hereditary RLS, we
      analysed the clinical data of 300 RLS patients. All 300 patients diagnosed as RLS
      according to the criteria of the International RLS Study Group were examined
      using a standard questionnaire covering demographic data, family history,
      clinical symptoms, subjective sleep disturbances and course of the disease. In
      all patients a complete neurological examination was performed, and in selected
      cases electrophysiological examinations and polysomnographic studies. Family
      history was rated as definitely positive when at least one first-degree relative
      was examined and classified as RLS according to the criteria by one of the
      authors. If it proved impossible to contact family members to verify reports of a
      family history, the patients were classified as only having a "possible positive
      family history." 232 of the 300 patients had iRLS and 68 secondary RLS due to
      uremia (uRLS). 42.3% of the patients with iRLS and 11.7% of those with uRLS were
      classified as having "definite positive" hereditary RLS, with a further 12.6% of
      iRLS patients and 5.8% of uRLS patients as having "possible positive" hereditary
      RLS. Patients with definite hereditary RLS were significantly younger at the age
      of onset than those with a negative family history (35.45 vs. 47.17 years, p <
      0.05). The clinical characteristics of the disease were similar in both groups,
      except that women with hereditary RLS experienced a worsening of symptoms during
      pregnancy (19.1% vs. 2.6%, p < 0.05). Our study shows that patients with
      hereditary RLS may experience an earlier onset of the disease. Hereditary and non
      hereditary RLS present with similiar clinical signs and symptoms.

PMID- 10947028
TI  - Temporal characteristics of delta activity during NREM sleep in depressed
      outpatients and healthy adults: group and sex effects.
AB  - STUDY OBJECTIVES: The primary aim was to evaluate group and sex differences in
      delta activity across non-rapid eye movement (NREM) sleep in depressed patients
      and healthy controls. DESIGN: Repeated-measures ANOVA contrasted delta power,
      amplitude and incidence in the first three NREM periods (stages 2, 3, and 4) of
      sleep. The time course of delta activity was evaluated with exponential
      regressions. Age effects on delta were evaluated with linear regression analysis.
      SETTING: Two consecutive nights were spent in the laboratory, the first of which
      served as adaptation. PATIENTS OR PARTICIPANTS: Twenty-two (9 men, 13 women)
      symptomatic, but unmedicated, outpatients with major depressive disorder (MDD)
      and 23 healthy controls (15 men, 8 women) participated in the study. MEASUREMENTS
      AND RESULTS: Delta power and amplitude showed significant group by sex
      interactions. Men with MDD showed lower power and amplitude in NREM sleep
      compared to women with MDD, but did not differ significantly from controls.
      However, the time course of delta power and amplitude was significantly different
      in men with MDD, with lower accumulation and slower dissipation across NREM sleep
      than all other groups. Women with MDD showed no evidence of lower delta power and
      amplitude or an abnormal time course compared to control women or men. Age had a
      differential influence on delta activity between the groups, with little age
      related change in delta activity in the depressed groups. CONCLUSIONS: It was
      concluded that slow-wave sleep deficiencies may be characteristic of men, but not
      women, with MDD. It was also concluded that the influence of age on delta
      activity varied as a function of both psychiatric status and sex.

PMID- 10947029
TI  - Pre-eclampsia is associated with marked alterations in sleep architecture.
AB  - STUDY OBJECTIVES: Pre-eclampsia is currently the predominant cause of maternal
      and fetal morbidity and mortality. Diurnal blood pressure variation is flattened
      or reversed in pre-eclampsia; however, sleep has not been extensively
      investigated in this disease. Our objective was therefore to study sleep
      architecture in this group of patients. STUDY DESIGN: Full polysomnography using
      the Compumedics Sleepwatch System or Compumedics p-series. SETTING: NA. PATIENTS:
      25 pre-eclamptic patients and 17 primigravidas with normal pregnancies and no
      history of cardiovascular disease or sleep disorder. With the exception of one
      subject, all pre-eclamptics were taking clonidine (a known suppressant of rapid
      eye movement-REM-sleep) for control of their hypertension. INTERVENTIONS: NA.
      RESULTS: Pre-eclamptic subjects had markedly altered sleep architecture, with a
      markedly increased percentage of time spent in slow-wave sleep (SWS) (21 * 2%
      versus 43 * 3%, p<0.001). There was a longer latency to rapid eye movement (REM)
      sleep (92 * 11 mins vs. 205 * 23 mins in control and pre-eclamptic subjects,
      respectively, p<0.001) and reduced time spent in REM (18 * 1% and 10 * 2% in
      control and pre-eclamptic subjects, respectively, p<0.001). CONCLUSIONS: While
      the increased REM latency and decreased REM time are most likely due to
      clonidine, this is unlikely to also account for the increased SWS. Two possible
      explanations for this include cerebral edema and release of cytokines, which are
      known to alter sleep structure.

PMID- 10947030
TI  - Associations between retrospectively recalled napping behavior and later
      development of Alzheimer's disease: association with APOE genotypes.
AB  - To evaluate putative risk factors for Alzheimer's disease (AD), we conducted a
      case-control study with exposure assessment performed after disease onset. In
      this study, we evaluated the effect of recalled habitual napping according to its
      duration and examined whether APOE genotype modifies the effect. The subjects
      were 337 patients (144 men, 193 women, age at onset and the time of study
      (years): 69+/-10, 73+/-9) with a diagnosis of probable AD based on the NINCDS
      ADRDA criteria. Two hundred and sixty spouses of the subjects (94 men, 166 women,
      age at the time of study: 69+/-9) served as controls. We asked retrospectively
      about habitual (3 or more days per week) napping and its duration observed
      between 5 and 10 years before the onset of AD for cases, and between 5 and 10
      years before the time of the study for controls. The analysis revealed that
      limited napping for up to 60 min had an apparently protective effect against the
      development of AD, especially for carriers of the APOEepsilon 4 allele. By
      contrast, napping for more than 60 min increased the risk of AD morbidity among
      the carriers of the allele. Habitual napping may modulate or disturb the
      physiological functions of sleep and circadian time-keeping according to its
      duration, and this might be associated with some mechanism that leads to the
      development of AD.

PMID- 10947031
TI  - Chiari malformation and sleep-disordered breathing: a review of diagnostic and
      management issues.
AB  - Chiari Malformation (CM) encompasses several patterns of congenital or acquired
      cerebellar herniation through the foramen magnum. This may result in brain-stem
      compression that impacts control of breathing and is associated with obstructive
      and central apneas. A high clinical suspicion for sleep-disordered breathing is
      needed in the care of such patients after as well as before corrective surgery.
      To introduce a review of CM with a focus on the relevance to sleep medicine, we
      present a case of a 13-year-old female who was diagnosed with CM Type 1 in the
      course of an evaluation of symptomatic central sleep apnea. After initial
      improvement following surgery there was recurrence of brain-stem compression. The
      only clinical expression of which was polysomnographically evident recurrence of
      sleep apnea.

PMID- 10947032
TI  - A long-term randomized, cross-over comparison of auto-titrating and standard
      nasal continuous airway pressure.
AB  - This study is a 12-week randomized, cross-over, single-blind comparison of the
      tolerance, compliance, and symptomatic improvement obtained with standard nasal
      continuous positive airway pressure (CPAP) vs. an auto-titrating, self-adjusting
      device (APAP). Sixty newly diagnosed patients, 53 with obstructive sleep apnea
      (OSA) and seven with upper airway resistance syndrome were studied. Thirty-nine
      patients (65%) completed the 24-week protocol. Data were complete in 33. In these
      33 patients CPAP and APAP reduced the Epworth Sleepiness score from 15+/-1 (+/
      SEM) to 8+/-1 and 9+/-1 respectively (both <0.0001 from baseline but NS between
      modes). The APAP average pressure was lower than the CPAP pressure, 6.4+/-0.4 and
      10.6+/-0.4 cm H20, respectively. The average daily machine use was greater with
      APAP, 6.0+/-0.3 hrs. versus 5.5+/-0.3 hrs. with CPAP (P < 0.04). The number of
      days of machine use, and the pattern of use were not different between CPAP and
      APAP. A higher proportion of patients who did not complete the study was
      randomized to CPAP for their initial treatment period. This study showed that: 1)
      CPAP and APAP produced an equivalent improvement in daytime sleepiness, 2) APAP
      pressure was lower than CPAP pressure, 3) patients wore the APAP device longer
      during nights they used the pressure support system, and 4) patients who began
      the study with APAP were more prone to continue treatment. We conclude that APAP
      was better tolerated and used a greater number of hours than CPAP, but the extent
      of improvement in excessive daytime sleepiness was similar between the two modes
      of therapy.

PMID- 10947033
TI  - Slow-release caffeine: a new response to the effects of a limited sleep
      deprivation.
AB  - STUDY OBJECTIVES: The aim of this study is to assess the interest of the intake
      of a new galenic form of caffeine called "slow-release" caffeine (SR caffeine)
      during a decrease of vigilance due to a limited sleep deprivation. DESIGN: The
      controlled method used compared three doses of SR caffeine (150, 300 and 600 mg)
      with a placebo. Tests were performed 2, 9 and 13 hours after each treatment.
      Wakefulness level was assessed subjectively through questionnaires and analog
      visual scales, and objectively with the Multiple Sleep Latency Test. Performance
      level was also assessed regularly with an attention test, a grammatical reasoning
      test, a spatial recognition test, a mathematical processing test, a visual
      tracking test, a memory search test, and a dual task. The motor activity was
      evaluated by wrist actimeter and safety of treatment was observed by regular
      clinical examination. SETTING: NA. PARTICIPANTS: Twenty-four young and healthy
      volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation.
      INTERVENTIONS: NA. RESULTS: The results show a significant effect of slow-release
      caffeine vs. placebo, and on vigilance and performance when subjects became
      tired. The effects of SR caffeine lasted 13 hours after treatment. SR caffeine
      300 and 600 mg are efficacious doses but the optimal dose (maximum effect without
      any side effects) for both men and women is after all 300 mg. Globally, there is
      no difference between placebo and caffeine during the recovery night period.
      CONCLUSIONS: SR caffeine (300 mg) seems to be an efficient and safety substance
      to maintain a good level of vigilance and performance during limited sleep
      deprivation.

PMID- 10947034
TI  - Hypnotic activity of melatonin.
AB  - OBJECTIVE: To establish the effect of melatonin upon nocturnal and evening sleep.
      METHODS: Experiment I: The effect of melatonin (0.1, 0.5, 1.0, 5.0, and 10 mg),
      ingested at 23:30, was studied on nocturnal sleep (23:30-07:30) and core body
      temperature in 8 healthy volunteers. Performance was measured 8.5 h post
      ingestion. On completion of the experiment dim light melatonin onsets (DLMO) were
      determined. Experiment II: The effect of melatonin (0.5, 1.0, 5.0, and 10 mg),
      ingested at 18:00, was studied on evening sleep (18:00-24:00) and core body
      temperature in 6 healthy volunteers. Performance was measured 6.5 h post
      ingestion. Each experiment was placebo-controlled and double-blind with a cross
      over design with temazepam (20 mg) as an active control. RESULTS: Experiment I:
      Melatonin (5 mg) reduced the duration of stage 3 in the first 100 min of sleep.
      Melatonin (0.1 mg) reduced body temperature 6.5 to 7 h post-ingestion. Temazepam
      increased stage 2, reduced wakefulness and stage 1, and increased the latency to
      REM sleep. Temazepam reduced body temperature 4.5 to 6.5 h post-ingestion. There
      were no changes in performance compared with placebo. DLMO occurred between 20:40
      and 23:15. Experiment II: Melatonin (all doses) increased total sleep time (TST),
      sleep efficiency index (SEI) and stage 2, and reduced wakefulness. Temazepam
      increased TST, SEI, stage 2 and slow-wave sleep, and reduced wakefulness. There
      were no changes in body temperature or performance compared with placebo.
      CONCLUSION: Melatonin given at 23:30 has no significant clinical effect on
      nocturnal sleep in healthy individuals. Hypnotic activity of melatonin when given
      in the early evening (presumably in the absence of endogenous melatonin) is
      similar to 20 mg temazepam.

PMID- 10947035
TI  - Inter-rater reliability for identification of REM sleep in Parkinson's disease.
AB  - Recently described functional connections between basal ganglia and brainstem
      circuits provide a neurobiologic basis for the absence of REM sleep atonia in
      Parkinson's disease (PD). However, identifying atypical REM sleep in PD may be
      problematic. Reliable sleep staging has never been demonstrated in such patients.
      In this study, 3 experienced scorers independently evaluated overnight
      polysomnograms from 10 (PD) patients. Results indicated good agreement for
      distinguishing REM from NREM sleep and waking. Reliable differentiation among
      NREM stages was more difficult to achieve. The results suggest that, despite
      suspension of REM sleep atonia accompanying PD, trained scorers can distinguish
      REM from wakefulness and NREM sleep.

PMID- 10947037
TI  - Bibliography of recent literature in sleep research.

PMID- 10947036
TI  - Rates of sensor loss in unattended home polysomnography: the influence of age,
      gender, obesity, and sleep-disordered breathing.
AB  - OBJECTIVES: To evaluate study failure and sensor loss in unattended home
      polysomnography and their relationship to age, gender, obesity, and severity of
      sleep-disordered breathing (SDB). DESIGN: A cross-sectional analysis of data
      gathered prospectively for the Sleep Heart Health Study (SHHS). SETTING:
      Unattended polysomnography was performed in participants' homes by the staff of
      the sites that are involved in SHHS. PARTICIPANTS: 6,802 individuals who met the
      inclusion criteria (age >40 years, no history of treatment of sleep apnea, no
      tracheostomy, no current home oxygen therapy) for SHHS. RESULTS: A total of 6802
      participants had 7151 studies performed. 6161 of 6802 initial studies (90.6%)
      were acceptable. Obesity was associated with a decreased likelihood of a
      successful initial study. After one or more attempts, 6440 participants (94.7%)
      had studies that were judged as acceptable. The mean duration of scorable signals
      for specific channels ranged from 5.7 to 6.8 hours. The magnitudes of the effects
      of age, gender, BMI, and RDI on specific signal durations were not clinically
      significant. CONCLUSION: Unattended home PSG as performed for SHHS was usually
      successful. Participant characteristics had very weak associations with duration
      of scorable signal. This study suggests that unattended home PSG, when performed
      with proper protocols and quality controls, has reasonable success rates and
      signal quality for the evaluation of SDB in clinical and research settings.

PMID- 10947038
TI  - Open mitral commissurotomy: the 'golden standard'.
AB  - BACKGROUND AND AIM OF THE STUDY: Percutaneous balloon mitral commissurotomy
      (PBMC) has recently emerged as an alternative to surgical commissurotomy for the
      treatment of rheumatic mitral valve stenosis. However, this blind procedure may
      result in incomplete separation of the commissures, which could lead to
      accelerated restenosis. Hence, open mitral commissurotomy (OMC), which is a
      visually oriented procedure, remains our method of choice. This study was aimed
      at assessing the long-term outcome of the OMC procedure. METHODS: A series of OMC
      performed between 1988 and 1991, involving 100 mitral valves, each with a
      preoperative echocardiographic score < or =10 was investigated clinically and by
      echocardiography. RESULTS: Postoperatively, the mean valve area achieved was
      2.89+/-0.49 cm2, compared with a mean preoperative value of 0.99+/-0.23 cm2. In a
      recent follow up, conducted after a mean of 8.5 years (range: 7-11 years), the
      mean valve area measured by echo-Doppler in this patient group was 2.37+/-0.42
      cm2 (range: 1.6 - 3.6 cm2), and 81% of patients had a valve area >2.0 cm2.
      Reoperation was required in only two cases. The late mortality rate was 4%
      (0.5%/pt-yr), and was in no case valve-related. Two-thirds of the patients had no
      or only mild mitral insufficiency, and 93% were in NYHA functional class I or II.
      The nine-year actuarial survival rate was 96%, freedom from reoperation 98%, and
      freedom from all valve-related complications 92%. Complementary to this
      experience, during the past 10 years we have performed modified OMC in 919 (79%)
      of all 1,151 patients with mitral stenosis submitted for surgery, including 257
      with mixed disease. The mean post-commissurotomy valve area (2.9 cm2) was
      identical to that of the study group. Moderate to severe valve calcification was
      not an absolute contraindication to valve conservation. CONCLUSION: OMC remains
      the best alternative for the treatment of all cases of mitral stenosis,
      independently of the degree of pliability. In our experience, the medium- and
      long-term results are significantly better than those usually reported in PBMC
      series.

PMID- 10947039
TI  - Mitral valve annuloplasty: comparison of the mural annulus shortening suture
      (MASS) with the Carpentier-Edwards prosthetic ring.
AB  - BACKGROUND AND AIM OF THE STUDY: Although mitral annuloplasty is an important
      element of mitral valve repair, the technique employed remains controversial. In
      this prospective study, we compared two different annuloplasty techniques with
      regard to hemodynamic performance. METHODS: Between October 1995 and December
      1998, 109 consecutive patients underwent mitral valve repair for mitral
      regurgitation. One group of patients (n = 55) received a Carpentier-Edwards (CE)
      ring for annuloplasty, and a second group (n = 54) underwent the mural annulus
      shortening suture (MASS) to reinforce the posterior circumference of the annulus.
      All patients were investigated prospectively by Doppler echocardiography before
      discharge and annually thereafter. The mean follow up was 22.7+/-11.6 months.
      RESULTS: The early mortality rate was 3.7%, with four early deaths in the CE
      group, and no early death in the MASS group. There was one late death in each
      group. One patient in each group required reoperation for severe mitral
      regurgitation after 19 and 30 months, respectively. Postoperative (12 months)
      Doppler echocardiography showed mean mitral valve gradients to be significantly
      lower (1.7+/-0.7 versus 2.7+/-1.7 mmHg; p <0.01) and mitral valve areas
      significantly larger (3.3+/-1.0 versus 2.6+/-0.7 cm2; p <0.01) in MASS patients
      compared with CE patients. There was no significant difference in mean
      postoperative mitral regurgitation between the two groups (0.5+/-0.2 versus 0.4+/
      0.2). CONCLUSION: Both annuloplasty techniques showed excellent results; however,
      hemodynamic performance of MASS was superior to that of the rigid CE ring, while
      not increasing postoperative mitral regurgitation. Therefore, MASS may be
      recommended as an alternative to annuloplasty rings, if future long-term follow
      up studies confirm the durability of the technique.

PMID- 10947040
TI  - Mitral valve repair: the Manipal alternative.
AB  - BACKGROUND AND AIM OF THE STUDY: An easily reproducible, rational and durable
      method of repairing the incompetent mitral valve, which does not require complex
      chordal procedures or the use of an expensive prosthesis and long-term
      anticoagulation, remains a desirable goal. Here, we describe such a method that
      has been developed at our institute. METHODS: The step-wise repair comprises: (i)
      preparation of a ring from a 3 x 110 mm strip of Dacron felt covered with
      untreated autologous pericardium; (ii) mitral commissurotomy and mobilization of
      the subvalvular apparatus, when required; (iii) infolding of the small portion of
      flail unsupported mitral leaflet, when present, by interrupted stitches; (iv)
      anchoring of the pre-prepared ring to the mitral annulus with interrupted
      horizontal mattress sutures, the sutures on the posterior annulus stopping short
      of the commissures by 12-15 mm and on the anterior annulus by 8-10 mm; (v)
      excision of the unanchored portions of the ring opposite the commissures, leaving
      behind 76-84 mm of the anchored parts; (vi) placement of two 'U-on-side'
      pericommissural annuloplasty sutures passed through the cut ends of the
      incomplete ring, then through the respective annulus, and finally emerging near
      the anterolateral and posteromedial commissures; and (vii) tying off the two
      pericommissural sutures over Teflon pledgets. RESULTS: Between January 1988 and
      December 1997, the technique was used to repair 107 mitral valves. Among 90
      patients who had mitral valve repair alone or combined with tricuspid or aortic
      valve repair, only one hospital death occurred. One patient required reoperation
      due to an unacceptable degree of hemolysis. Among survivors followed up from one
      to >10 years, 80% were in NYHA functional class I, and 70% did not have clinical
      mitral regurgitation. CONCLUSION: This alternative technique of mitral valve
      repair is simple to perform, and relatively inexpensive. It provides gratifying
      results in acquired mitral valve disease, as well as in mitral valve prolapse
      subjects, and the repaired valve appears to function well, even after 10 years.

PMID- 10947041
TI  - Geometric distribution of chordae tendineae: an important anatomic feature in
      mitral valve function.
AB  - BACKGROUND AND AIM OF THE STUDY: This study examined the geometric distribution
      of chordae tendineae and their importance in compensating for papillary muscle
      (PM) displacement. METHODS: Anatomic, chordal mechanics and hemodynamic
      measurements were performed with porcine mitral valves. For hemodynamic
      measurements, physiological pulsatile flow conditions were maintained, and PM
      positions varied. Leaflet coaptation was documented by 2-D echocardiography, and
      regurgitation measured directly. RESULTS: Anatomic measurements showed the sum of
      marginal leaflet and marginal chordal lengths to exceed basal chordal length
      (1.8+/-0.4 versus 2.8+/-0.7 cm for anterior leaflets; 1.6+/-0.3 versus 2.5+/-0.6
      cm for posterior leaflets). Triangular structures existed between basal chordae
      and marginal chordae with the marginal leaflet as the third side. Basal chordae
      resisted apical PM displacement in static experiments, while marginal chordae
      governed leaflet closure in hemodynamic experiments. Under pulsatile flow
      conditions, apical PM displacement decreased leaflet coaptation length and
      increased regurgitation (9.4+/-2.1 versus 4.0+/-1.6 ml). When marginal chordae
      were fused to the basal chordae, eliminating the role of the marginal chordae,
      severe regurgitation resulted (28.5+/-5.0 ml with apical PM displacement).
      CONCLUSION: Based on triangular structures involving the basal and marginal
      chordae, a compensatory mechanism was described which explains how the severity
      of mitral regurgitation can vary following PM displacement. Basal chordae provide
      a constant connection between the annulus and papillary muscles, while marginal
      chordae maintain marginal leaflet flexibility, governing proper valve closure.
      This study relates chordal distribution to normal valve function, and provides a
      better understanding of breakdown in valve function under pathophysiological
      conditions.

PMID- 10947042
TI  - Influence of HLA matching and associated factors on aortic valve homograft
      function.
AB  - BACKGROUND AND AIM OF THE STUDY: Evidence suggests that the implanted aortic
      valve homograft suffers eventual loss of function due to early donor-specific
      antibody and T cell-mediated responses to human leukocyte antigens (HLA). The
      association between rejection/dysfunction and donor/recipient HLA mismatch for
      vascularized organ homografts has not been revealed for aortic valve homografts.
      An aortic valve homograft recipient cohort was studied to determine whether HLA
      mismatch and associated factors predicted homograft dysfunction. METHODS: Both
      donor and recipient HLA type was obtained for 162 recipients of cryopreserved
      aortic valve homografts between 1986 and 1998. Structural deterioration of the
      homograft was defined by echocardiography as at least moderate aortic stenosis or
      regurgitation. Patients' records were searched for postoperative fever, ABO blood
      type disparity, and other associated factors. HLA class 1 (A and B antigens) were
      typed serologically, and HLA class 2 (DR antigens) by molecular genotyping.
      Associations were analyzed using chi-square tests and Kaplan-Meier curves of
      freedom from structural deterioration in all patients, and in those with > or =5
      years of follow up. Cox regression was used to determine independent predictors
      of structural deterioration. RESULTS: Class 2 antigen mismatch had a significant
      association (p = 0.04) with decrease in cryopreserved aortic valve homograft
      freedom from structural deterioration in patients with long-term follow up (> or
      =5 years). In addition, there was an important difference in frequency of
      postoperative fever in recipients with two DR mismatches (31.2%), and in those
      with no or one DR mismatch (16.9%; p = 0.051). Significant associations were not
      found between homograft dysfunction and HLA mismatch at the class-1 loci. Young
      age at operation and short time (<4 h) between homograft procurement and
      cryopreservation were associated with an increase in structural deterioration.
      CONCLUSION: The association between aortic valve homograft dysfunction and HLA DR
      mismatch suggests that elements of the anti-donor immune response penetrate and
      damage the homograft. A similar link to postoperative fever indicates that immune
      stimulation may be an early event. Further investigation will reveal the exact
      pathways by which this occurs and by which therapy (immunosuppression of the
      recipient, genetic engineering of the donor graft, or other techniques) this
      recipient anti-donor response can be modified.

PMID- 10947043
TI  - Lack of ABH-antigen expression on human cardiac valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Seeding of heart valve prostheses with human
      umbilical vein endothelial cells (HUVEC) and human saphenous vein endothelial
      cells (HSVEC) has been applied to create a viable valve surface and improve valve
      performance. HUVEC and HSVEC are well characterized and have been used as a model
      of endothelial antigenicity, but antigenicity of the valve endothelium is less
      well characterized. To clarify this issue, we studied the expression of blood
      group antigens by human valvular endothelium, HSVEC and HUVEC. METHODS: Human
      aortic and mitral valves and myocardial tissue were freshly harvested from
      explanted hearts of patients undergoing heart transplantation (blood group A, n =
      4; group O, n = 4) or valve replacement (blood group B, n = 4). After fixation in
      Carnoy's or formalin solution, paraffin sections were stained with anti-A (blood
      group A), anti-B (blood group B), and anti-H (blood group O) antibodies. Human
      umbilical cords were freshly harvested postpartum, and human saphenous veins were
      obtained from patients undergoing coronary bypass grafting (each blood group, n =
      2) and similarly fixed and stained to detect ABO antigens. The preservation of
      endothelium was confirmed by staining with anti-CD 31 monoclonal antibody. All
      sections were examined by light microscopy. RESULTS: CD 31 staining demonstrated
      vascular and valve endothelial preservation. Human umbilical cords, saphenous
      vein and myocardium showed strongly expressed A, B and H blood group antigens on
      vascular endothelium. However, no A, B and H antigens were detected on the
      valvular endothelium. CONCLUSIONS: Valve endothelial cells appear to be a class
      of specialized endothelial cells that does not express the ABO antigens. Due to
      the strong expression of A, B and H antigens by HUVEC and HSVEC blood group cross
      matching should be considered for non-autologous endothelialization of valve
      prostheses.

PMID- 10947044
TI  - The quality of heart valve tissue for homograft transplantation.
AB  - BACKGROUND AND AIM OF THE STUDY: The results of heart valve replacement surgery
      may be improved by refining surgical techniques and/or developing new heart valve
      transplants. The aim of this study was to examine the effect of age on the
      presence of cholesterol clefts and lipid deposits in the cusp base and sinus wall
      of aortic homografts. METHODS: Seventy-one valves were obtained at autopsy from
      donors (aged 15- 40 years) with no history of illness or evidence of serious
      illness. Trauma was the predominant cause of death among patients. The valves
      were examined using an osmium-vaporization technique. RESULTS: Osmiophilic
      deposits were detected in the cusp base in 28 cases (42%), and in the sinus wall
      in 49 cases (69%). Cholesterol crystals in the cusp base were found in 16 cases
      (24%), and sinus wall cholesterol clefts in 26 cases (38%). The model-predicted
      probability of cusp base lipid deposits existing was 76% in 40-year-old donors,
      36% in 30-years-olds, and 11% in 20-year-olds; the probability of cusp base
      cholesterol clefts existing was 45%, 21% and 8% in these age groups,
      respectively. The influences of immunological reactions, biochemical changes
      (centers of calcification) and acceleration of atherosclerotic processes are
      discussed. CONCLUSION: The microscopic study of heart valves demonstrated the
      presence of lipid deposits in subjects of an unexpectedly young age. Among our
      study material, 58% of valves obtained from donors aged 11-40 years were
      unsuitable for transplantation. Our results confirmed the need for macroscopic
      inspection of heart valves before their being transplanted.

PMID- 10947045
TI  - Cardiovascular tissue banking in the non-cadaveric setting: ten-year experience
      of a university hospital-based bank with active organ donation program.
AB  - BACKGROUND AND AIM OF THE STUDY: Today, transplantation of cardiovascular tissues
      is common practice, and tissue banking has become routine. Consequently, many
      institutions exist which carry out high-quality tissue banking. METHODS: The
      Hospital Clinico of the University of Barcelona established its cardiovascular
      tissue bank in 1989. The bank follows international and national regulations, and
      functions as a non-profit-making organization. Organ and tissue donors are
      recruited by the Transplant Coordination unit, which works closely with the
      Catalonian Organ Transplant Network (OCAT) and the Spanish National Organ
      Transplantation Network (ONT). The hearts are removed during multi-organ donation
      and processed using aseptic techniques in a laminar flow hood. Hearts are only
      accepted from brain-dead multiorgan and non-beating-heart donors. The heart
      valves are dissected, decontaminated, cryopreserved in specific media and stored
      in liquid nitrogen at -196 degrees C under strict bacteriological and serological
      control. RESULTS: Between 1989 and 1999, a series of 1,005 cardiovascular donors
      from within Spain was identified, from which 840 hearts were processed. After
      evaluation, 1,099 (65.4%) valves were cryopreserved, and 1,023 (61.5%) given
      clearance for implantation. In total, 534 aortic, 530 pulmonary, 33 mitral and
      two tricuspid valves were processed; ultimately 92.8% of aortic and 93.9% of
      pulmonary valves were accepted for clinical implantation. The rejection rate was
      39.1%. Homografts were transported to their destination in dry ice in a cryogenic
      container. Overall, 608 valves were implanted at our own institution and at
      hospitals in Barcelona and Europe. Only two cases of complaint were received from
      implanting surgeons. CONCLUSION: After ten years' experience, the degree of
      satisfaction of implanting surgeons appears to be adequate. Strict control of the
      entire tissue banking process has permitted the availability of high-quality
      homografts for clinical implantation.

PMID- 10947046
TI  - Carpentier-Edwards porcine bioprostheses: clinical performance assessed by actual
      analysis.
AB  - BACKGROUND AND AIM OF THE STUDY: The clinical performance of porcine
      bioprostheses for valve replacement has been evaluated for over three decades by
      actuarial analysis as the standard for reporting time-related results. Actual or
      cumulative incidence analysis provides a complementary method to determine the
      manifestations of valve-related complications due primarily to structural valve
      deterioration. Valve-related mortality and reoperation of porcine bioprostheses
      for aortic and mitral valve replacement was compared by actuarial and actual
      methodology. METHODS: The Carpentier-Edwards porcine bioprostheses were implanted
      between 1975 and 1995 as 2,237 aortic valve replacements (AVR) and 1,582 mitral
      valve replacements (MVR). Coronary artery bypass was performed in 36.4% of AVR,
      and 30.6% of MVR. Fatal valve-related complications occurred in 7.6% of AVR and
      11.3% of MVR. The cumulative follow up was 14,810 patient-years (mean 6.6 years)
      for AVR and 9,718 patient-years (mean 6.1 years) for MVR. RESULTS: Patient
      survival, and actuarial and actual freedom from valve-related mortality and valve
      related reoperation was reported at 15 years. For AVR, survival in the 61-70
      years age group was 30.9%, freedom from valve-related mortality was 79.3% and
      86.9% respectively, and freedom from valve-related reoperation 79.0% and 88.1%
      respectively. For AVR, survival in the >70 years age group was 18.1%, freedom
      from valve-related mortality 72.8% and 84.9% respectively, and freedom from
      reoperation 86.3% and 96.1% respectively. For MVR, survival in the 61-70 years
      age group was 16.1% at 15 years, freedom from valve-related mortality was 59.5%
      and 79.5% respectively, and freedom from valve-related reoperation 32.6% and
      71.0% respectively. For MVR, survival in the >70 years age group was 2.8% at 15
      years, valve-related mortality was 26.1% and 82.0% respectively, and freedom from
      valve-related reoperation 83.4% and 93.3% respectively. CONCLUSION: The actual
      freedom from valve-related mortality and valve-related reoperation (primarily
      from structural valve deterioration), provides further evidence to consider
      porcine bioprostheses for AVR in patients aged >60 years, and for MVR in patients
      aged >70 years. The freedom from valve-related mortality supports the use of
      porcine bioprostheses for MVR in patients aged 61-70 years. Patient survival is
      influenced to the greatest extent by factors other than valve-related mortality.

PMID- 10947047
TI  - Impact of high transvalvular velocities early after implantation of Freestyle
      stentless aortic bioprosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: Stentless aortic bioprostheses have excellent
      hemodynamics, although heterogeneity in gradients has been observed. The present
      study was intended to determine whether high early postoperative transvalvular
      velocities correlate with other measures of left ventricular outflow obstruction,
      whether the phenomenon is transient, and whether high velocities observed early
      after surgery predict differences in subsequent valve performance or left
      ventricular remodeling. METHODS: Sixty-eight consecutive patients who underwent
      implantation of Freestyle stentless aortic bioprosthesis and survived to hospital
      discharge underwent early postoperative echocardiography. Peak transvalvular
      velocity was used to define a 'high-velocity' group, based on mean (+ 1 SD) for
      the group. Mean pressure gradient, ratio of peak to proximal velocities, and
      effective orifice area were assessed; change in peak velocity and evidence of
      left ventricular mass regression were studied at one-year follow up. RESULTS: Of
      68 patients, 14 (21%) had 'high velocities' based on early postoperative peak
      transvalvular velocity >3.0 m/s. There was a higher prevalence of women (64%
      versus 33%, p = 0.04), and both body surface area (1.79+/-0.17 versus 1.95+/-0.20
      m2, p = 0.01) and implanted valve size (22.9+/-2.0 versus 24.9+/-2.1 mm, p =
      0.003) were smaller among the 'high-velocity' group. High velocity correlated
      with other measures of resistance to left ventricular outflow, including higher
      mean gradient (20.9+/-6.5 versus 8.3 +/-4.2 mmHg, p <0.001) and lower effective
      orifice area (1.15+/-0.36 versus 1.69+/-0.62 cm2, p <0.001). High early
      postoperative velocities persisted at one year in eight of 13 (62%) patients.
      Left ventricular mass regression occurred less often in the 'high-velocity' group
      (38% versus 77% of patients, p = 0.03) and was present in only one of eight (12%)
      patients in whom high velocity persisted at one year. CONCLUSION: High early
      postoperative transvalvular velocity suggests resistance to left ventricular
      outflow. High velocities are transient in some patients, although persistence of
      high transvalvular velocity suggests 'prosthesis-patient mismatch' with
      incomplete relief of left ventricular outflow obstruction.

PMID- 10947048
TI  - The Quattro valve and active infective endocarditis of the mitral valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Even today, infective endocarditis remains a
      therapeutic challenge. Active endocarditis at the time of valve implantation is
      an important risk factor for the development of prosthetic valve infection. This
      study reports results following implantation of the Quattro valve, a stentless
      chordally supported quadrileaflet mitral valve made from bovine pericardium.
      METHODS: The Quattro valve was implanted in seven patients (four females, three
      males; mean age 34 years) requiring isolated mitral valve replacement for active
      bacterial endocarditis. All had congestive heart failure; two were in cardiogenic
      shock. The diagnosis of active endocarditis was based on clinical and
      echocardiographic findings, together with macroscopic evidence of acute infection
      at surgery, blood culture or histopathological evidence of valve infection.
      Postoperatively, all patients received at least four weeks of parenteral
      antibiotic therapy. RESULTS: Congestive heart failure (and large pedunculated
      vegetations and mobile septic left atrial thrombi in two patients) prompted early
      surgical intervention. Patients underwent surgery at a mean of 7 days (range: 1
      16 days) after admission. Endocarditis was caused by Gram-positive cocci in all
      patients except one. At a mean follow up of 15 months (range: 6-24 months) all
      patients were alive and symptomatically improved. To date, all remain free of
      prosthetic valve endocarditis, reoperation and thromboembolism. CONCLUSION: The
      Quattro valve can be implanted safely in patients with acute bacterial
      endocarditis. The results also reflect the benefit of early surgical intervention
      in patients with infective endocarditis complicated by congestive heart failure,
      with or without large vegetations.

PMID- 10947049
TI  - The influence of stenting on the behavior of amino-oleic acid-treated,
      glutaraldehyde-fixed porcine aortic valves in a sheep model.
AB  - BACKGROUND AND AIM OF THE STUDY: The durability of freehand-sewn aortic valve
      homografts used for valve replacement in humans is greater than for stented
      aortic homografts. In analogy with this, it is expected that the durability of a
      stentless heterograft will be superior to that of its stented counterpart. Our
      objective was to investigate the influence of stenting on amino-oleic acid (AOA)
      treated, glutaraldehyde-fixed porcine aortic valve bioprostheses. METHODS: Twelve
      young sheep underwent implantation of porcine aortic valves in the pulmonary
      artery: six porcine aortic stentless valves (Freestyle) and six porcine aortic
      stented valves (Mosaic). In each series, three valves were explanted after three
      months, and three after six months. Valves were analyzed by gross inspection,
      radiography, histology, and transmission electron microscopy. Quantitative
      determination of calcium content was made with atomic absorption spectrometry.
      RESULTS: The porcine aortic stentless valve showed extensive calcification of its
      aortic wall portion, but had perfectly functioning, pliable cusps without
      calcification up to six months. The cusps of porcine aortic stented valves were
      also pliable and functioning without calcification up to six months. Only minimal
      calcification was seen in the aortic wall of the stented valves. At six months
      after implantation the cusps of stentless valves contained significantly less
      calcium than those of stented valves (2.7+/-1.2 microg/mg and 7.9+/-2.3
      microg/mg, respectively; p = 0.011). However, the aortic wall from stentless
      valves contained significantly more calcium than that of stented valves (three
      month explants: 39.2+/-14.4 versus 7.2+/-2.8 microg/mg; p <0.05; six-month
      explants: 49.3+/-14.0 versus 14.1+/-5.9 microg/mg; p <0.05). CONCLUSION: These
      data suggest that stenting does influence cuspal calcification of AOA-treated,
      glutaraldehyde-fixed porcine aortic valves.

PMID- 10947050
TI  - Prevention of glutaraldehyde-fixed bioprosthetic heart valve calcification by
      alcohol pretreatment: further mechanistic studies.
AB  - BACKGROUND AND AIM OF THE STUDY: Calcification is a major cause of failure of
      bioprosthetic heart valves derived from glutaraldehyde-crosslinked bovine
      pericardium or porcine aortic valve (PAV) cusps. Recently, we have shown that
      ethanol pretreatment of PAV cusps prevents calcification in animal models.
      METHODS AND RESULTS: In this study we showed that ethanol pretreatment was
      equally effective in preventing calcification of glutaraldehyde-crosslinked
      bovine pericardium (control Ca2+ = 121.16+/-7.49 microg/mg tissue; ethanol
      pretreated Ca2+ = 2.95+/-0.78 microg/mg). Furthermore, other low-molecular weight
      alcohols such as methanol and isopropanol were also effective in mitigating
      calcification of PAV cusps. Storage of ethanol-pretreated cusps in glutaraldehyde
      before implantation allowed partial return of calcification, suggesting a role
      for ethanol-glutaraldehyde interactions in preventing calcification. However,
      when ethanol-pretreated cusps were stored in ethanolic glutaraldehyde up to one
      month, the anti-calcification effect of ethanol persisted. The conditions whereby
      PAV cusps were crosslinked in pure, non-aqueous, alcoholic glutaraldehyde
      solutions were also examined. The crosslinking was equivalent to the standard
      aqueous glutaraldehyde crosslinking as indicated by thermal denaturation
      temperatures (Td) obtained by differential scanning calorimetry (DSC) and
      resistance to collagenase digestion. However, these cusps had lower water content
      and showed a marked decrease in spin-lattice relaxation times (T1) obtained by
      solid-state proton nuclear magnetic resonance (NMR). Moreover, these cusps
      calcified heavily in the 21-day rat subdermal implants. Thus, alcohol treatment
      during glutaraldehyde crosslinking was not useful. CONCLUSION: Glutaraldehyde
      storage after ethanol pretreatment aggravates calcification; moreover, alcoholic
      glutaraldehyde crosslinking solutions are not beneficial for anti-calcification.
      Ethanol pretreatment of glutaraldehyde-pretreated bovine pericardium prevents its
      calcification.

PMID- 10947051
TI  - Is 10 minutes the optimum immersion time in 0.6% glutaraldehyde for human
      pericardium?
AB  - BACKGROUND AND AIM OF THE STUDY: Pericardial fixation with 0.6% glutaraldehyde is
      usually assessed by measuring the shrinkage temperature of the tissue: the higher
      the shrinkage temperature, the greater the degree of cross-linking induced
      between collagen molecules. Animal pericardium studies have shown maximum
      response to be obtained after brief immersion (10 min). Our aim was to evaluate
      the effect of glutaraldehyde immersion time on shrinkage temperature of human
      pericardium which, to our knowledge, has not yet been studied. METHODS:
      Pericardial strips were harvested from 40 patients undergoing cardiac surgery.
      Time of immersion in glutaraldehyde ranged from 3 min to 6 months. Fresh
      untreated human pericardium samples were used as controls. The relationship
      between shrinkage temperature and time of treatment with glutaraldehyde was
      studied using a regression analysis. RESULTS: Glutaraldehyde treatment of
      pericardial tissues caused an increase in shrinkage temperature that was related
      biphasically to the time of immersion in glutaraldehyde. Mathematical expression
      of this curve permitted glutaraldehyde immersion time to be evaluated in relation
      to the degree of optimal shrinkage temperature. The time required for optimal
      fixation with glutaraldehyde, as measured by shrinkage temperature, was 100+/
      0.77 min. CONCLUSION: Our results suggested that a 10-min exposure to
      glutaraldehyde was insufficient for 'correct' fixation of human pericardium.
      Inadequate glutaraldehyde exposure of human pericardium may explain mid and long
      term failures reported with this tissue in cardiac surgery.

PMID- 10947052
TI  - A study of the junction between glutaraldehyde-treated allogeneic aorta and host
      aorta.
AB  - BACKGROUND AND AIM OF THE STUDY: Stentless aortic valve bioprostheses have become
      popular because of their superior hemodynamics and expected increased durability.
      However, the stentless bioprosthesis differs from stented valves in that
      glutaraldehyde (GA)-treated tissue is implanted in direct contact with the native
      aorta. The effect of GA-treated tissue on host tissue has not been reported.
      METHODS: In order to analyze the effect of GA in the healing process, sheep
      descending aortic conduits treated with 0.625% GA were inserted in the descending
      thoracic aorta of 10 adult sheep. The implants were removed after 4, 5, 10, 12,
      15, 25, 30, 32, 60 and 120 days. The upstream and downstream junctions were
      evaluated macro- and microscopically, and by immunohistology for smooth muscle
      cell alpha-actin and von Willebrand factor. RESULTS: By day 60 of implantation,
      the GA-treated conduits were calcified. By days 60 and 120, the calcification had
      spread to the host aorta, and was seen as foci of calcification in the junctional
      area. Acellular areas were also seen in the host aorta near the anastomosis. A
      fibrotic layer spanning the abluminal aspect of the junction between the implant
      and host aorta was present at day 4 and continued through 120 days. This layer
      was characterized by a progressive increase in collagenous matrix and
      cellularity, as well as new blood vessel formation. The luminal aspect of the
      junction had a neointimal layer of variable thickness containing alpha-actin
      expressing cells covered by a monolayer of von Willebrand factor-expressing
      cells, seen at 15-30 days and present through 120 days. CONCLUSION: In our model,
      implanting GA-fixed tissue in direct contact with living tissues resulted in cell
      death and calcification of host tissue within 60 days. The integrity of the
      junction did not appear to be compromised. This may be of interest in light of
      the increased popularity of the stentless aortic bioprosthesis.

PMID- 10947053
TI  - Preimplant ultrastructure and calcification tendency of various biological aortic
      valves.
AB  - BACKGROUND AND AIM OF THE STUDY: In recent years a number of fixation and anti
      calcification methods have been developed, but little is yet known about the
      calcification process of biological valves. The aims of this study were to: (i)
      perform a systematic ultrastructural investigation on various biological valves;
      and (ii) determine the extent of calcification of these valves in a subcutaneous
      rat model. METHODS: The following porcine aortic prostheses were investigated:
      Toronto-SPV, Intact, Freestyle, Mosaic and Hancock-II. Samples taken from the
      valve leaflets, and in the case of the Freestyle and Toronto-SPV valves also from
      the aortic wall, were examined ultrastructurally using scanning and transmission
      electron microscopy. Other samples were implanted subcutaneously in Wistar rats
      for 12 weeks. The calcium content of the samples was measured using atomic
      absorption spectrophotometry. RESULTS: All valves examined showed a considerable
      loss of the endothelial cover. Significant changes in valve ultrastructure were
      also detected. With regard to calcium content, two valve groups could be
      distinguished (p <0.05): (i) those with high calcium content, e.g. Toronto-SPV
      and Intact (>40 mg/g dry tissue); and (ii) those with low calcium content, e.g.
      Mosaic, Freestyle and Hancock-II (<5 mg/g). CONCLUSION: Fixation methods have
      pronounced effects on the ultrastructural integrity of bioprostheses. The
      degenerative calcification of bioprostheses can be effectively inhibited by
      glutaraldehyde-free fixation and anti-calcification treatments.

PMID- 10947054
TI  - Changes in left ventricular function and mass during serial investigations after
      valve replacement for aortic stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The potential for left ventricular hypertrophy
      regression and associated functional improvements may well be the underlying
      mechanism of results in general after valve replacement for aortic stenosis. The
      study aim was to investigate preoperative predictors and the time course of such
      ventricular changes. METHODS: Forty-six patients (mean age 61 years; range: 24-82
      years) with aortic stenosis were prospectively followed with serial
      investigations (Doppler echocardiography, radionuclide ventriculography) at eight
      days (n = 43), three months (n = 42) and 18 months (n = 39) after valve
      replacement with a mechanical valve (19-29 mm). The postoperative course of left
      ventricular ejection fraction (EF), fast filling fraction, mass index and end
      diastolic volume index (EDVi) was analyzed in an independent increments
      statistical model for repeated measurements. RESULTS: EF rose marginally, from
      59+/-15% preoperatively to 64+/-16% (p <0.05) at 18 months, independently related
      to preoperative EF (p = 0.0001) and fast filling fraction (p = 0.0001). Changes
      in fast filling fraction were similarly predicted by the preoperative starting
      point (p = 0.003) and by preoperative left ventricular systolic radius:wall
      thickness ratio (p = 0.0002) with an inverse relation (the larger the chamber and
      the poorer its contractility, the lower the postoperative fast filling fraction).
      Mass index was independently related to the time point of postoperative
      measurement, indicating continuing regression of hypertrophy, from 200+/-66 g/m2
      preoperatively to 148+/-49 g/m2 at 18 months (p <0.0001), when only 18% of the
      patients had normal mass index. Mass index was also independently related to
      preoperative left ventricular end-systolic dimension index (p = 0.0008) with a
      constant influence, and systolic wall stress (p = 0.0009) which was modified by
      time: the influence of wall stress was significant at eight days, weak at three
      months, and pronounced at 18 months. Left ventricular EDVi after surgery was
      inversely related to preoperative EF modified by time. Associated coronary artery
      disease, size of the prosthetic valve, and peak gradient across the valve (mean
      15 mmHg; range: 7-26 mmHg at 18 months) did not influence any of the four target
      variables. CONCLUSION: We conclude that left ventricular response to valve
      replacement for aortic stenosis is predictable. A significant reduction in
      hypertrophy occurs during the first 18 postoperative months, but to a normal
      ventricular mass in only a minority of patients. Insufficient regression of
      hypertrophy was related to indices of irreversible myocardial disease, which also
      prevented functional ventricular improvement despite successful valve replacement
      and a hemodynamically well functioning valve.

PMID- 10947055
TI  - Fluoroscopy of prosthetic heart valves: does it have a place in the
      echocardiography era?
AB  - Fluoroscopy is the best method for delineation of the radio-opaque elements of
      prosthetic heart valves. It is the modality of choice for the validation and
      quantification of leaflet motion abnormalities, and for the identification of
      structural valve dysfunction. Normal values are shown. Echocardiography and
      fluoroscopy may be seen as complementary diagnostic techniques and, when used
      appropriately, may help to evaluate prosthetic valve function, integrity and
      associated complications.

PMID- 10947056
TI  - Missed opportunities for prevention of tuberculosis among persons with HIV
      infection--selected locations, United States, 1996-1997.
AB  - Public health contact investigations are conducted to find persons who have been
      exposed to patients with active tuberculosis (TB) and to evaluate and treat those
      contacts for TB infection and active TB. Persons in close (i.e., prolonged,
      frequent, or intense) contact with patients with active TB are at high risk for
      TB infection. The risk for TB infection is increased greatly if the close contact
      is infected with human immunodeficiency virus (HIV) (1,2). Isoniazid (INH)
      treatment for latent TB infection (LTBI) reduces the riskfor developing active TB
      by 41%-92% (1). This study examined the clinic records of TB programs to
      determine whether these programs used recommended practices to manage HIV
      positive persons exposed to TB (3-8). The study suggests TB programs need to
      review their contact investigation policies, procedures, and outcomes to reduce
      missed opportunities for preventing active TB among HIV-positive close contacts.

PMID- 10947057
TI  - Assessment of infectious disease surveillance--Uganda, 2000.
AB  - In 1998, member states of the African region of the World Health Organization
      (WHO-AFRO) adopted the integrated disease surveillance (IDS) strategy to
      strengthen national infectious disease surveillance systems (1). The first step
      of the IDS strategy is to assess infectious disease surveillance systems. This
      report describes the results of the assessment of these systems of the Uganda
      Ministry of Health (UMoH) and indicates that additional efforts are needed to
      develop the basic elements of an effective surveillance system.

PMID- 10947058
TI  - Intimate partner violence among men and women--South Carolina, 1998.
AB  - Few studies provide population-based estimates of intimate partner violence (IPV)
      for men and women, especially at the state level. IPV may result in adverse
      health effects for victims and perpetrators (1-3). To estimate the lifetime
      incidence of IPV by type of violence (e.g., physical, sexual, and perceived
      emotional abuse) and to explore demographic correlates of reporting IPV among men
      and women, the South Carolina Department of Health and Environmental Control and
      the University of South Carolina conducted a population-based random-digit-dialed
      telephone survey of adults in the state. This report summarizes the results of
      the survey, which indicated that approximately 25% of women and 13% of men have
      experienced some type of IPV during their lifetime. Although women were
      significantly more likely to report physical and sexual IPV, men were as likely
      as women to report emotional abuse without concurrent physical or sexual IPV.

PMID- 10947059
TI  - Alloreactivity and apoptosis in graft rejection and transplantation tolerance.
AB  - Weissmann wrote as early as 1889 that higher organisms contain within themselves
      the germs of death [1]. However, the term, programmed cell death, or apoptosis as
      it is now known, was defined much later [2]. Thus, it was long recognized that
      damaged and old cells are eliminated within the body, but the underlying
      mechanisms are only now beginning to emerge. Apoptosis appears central to the
      process of negative selection of developing T-cells in the thymus. In regard to
      organ transplantation, apoptosis contributes to graft rejection and the
      establishment of graft tolerance. Thus, understanding the regulatory mechanisms
      of apoptosis may help establish a new protocol for the induction of
      transplantation tolerance.

PMID- 10947060
TI  - Innate and adaptive immunity in Candida albicans infections and saprophytism.
AB  - Underlying acquired immunity to the fungus Candida albicans is usually present in
      adult immunocompetent individuals and is presumed to prevent mucosal colonization
      progressing to symptomatic infection. Exploration of immunological events leading
      to Candida resistance or susceptibility has indicated the central role of the
      innate and adaptive immune systems, the relative contribution of which may vary
      depending on the site of the primary infection. Nevertheless, acquired resistance
      to infection results from the development of Th1 responses. Cytokines produced by
      Thl cells activate phagocytic cells to a candidacidal state. In contrast,
      cytokines produced by Th2 cells inhibit Th1 development and deactivate phagocytic
      effector cells. Because reciprocal influences have been recognized between innate
      and adaptive Th immunity, it appears that an integrated immune response
      determines the life-long commensalism of the fungus at the mucosal level, as well
      as the transition from mucosal saprophyte to pathogen.

PMID- 10947061
TI  - Influence of type 2 T cell responses on the severity of encephalitis associated
      with influenza virus infection.
AB  - The role of type 2 T cell responses on the severity of post-infectious
      encephalitis was investigated in a mouse model of influenza virus infection. When
      mice were infected intracerebrally with 3.0 LD(50) of A/NWS33 strain of influenza
      virus, they all showed clinical signs of encephalitis, and 90% of them died
      within 10 days of the infection. However, the post-infectious encephalitis was
      not demonstrated in mice exposed to 0.5 LD50 of the same virus. The mortality
      rates of mice infected with 0.5 LD(50) of the virus were increased to levels
      observed in mice exposed to 3.0 LD(50) of influenza virus infection, after the
      administration of a mixture of interleukin (IL)-4 and IL-10 (2 ng/mouse each;
      immediately, 1 and 2 days after the infection). In contrast, mortality rates of
      mice exposed to 3.0 LD(50) of influenza virus were substantially decreased when
      these mice were treated with a mixture of monoclonal antibodies directed against
      IL-4 and IL-10. A predominance of type 2 T cell responses was demonstrated in
      splenic T cells of mice infected with 3.0 LD(50) of influenza virus, although
      these responses were minimal in mice infected with 0.5 LD(50) of the virus. After
      the treatment with the mixture of type 2 cytokines, an increase in the type 2 T
      cell responses in mice exposed to 0.5 LD(50) of the virus was shown. These
      results indicate that type 2 T cell responses associated with the viral infection
      play an important role in the severity of post-infectious encephalitis induced in
      mice by the intracerebral infection of influenza A virus.

PMID- 10947062
TI  - Induction of neutrophil death resembling neither apoptosis nor necrosis by ONO-AE
      248, a selective agonist for PGE2 receptor subtype 3.
AB  - An increase of intracellular cAMP mediated by prostaglandin E2 (PGE2) has been
      shown to delay spontaneous apoptosis of neutrophils. It has been demonstrated
      that a selective agonist for PGE2 receptor subtype 3 (the EP3 receptor) is
      capable of decreasing cAMP and stimulating phosphoinositide turnover in various
      types of cells. We investigated the effect of a selective EP3 receptor agonist,
      ONO-AE-248, on neutrophil viability. ONO-AE-248 rapidly caused a unique form of
      neutrophil death. The agonist primarily induced morphological changes of the
      nucleus, including fusion of the lobules, decreased compactness of the chromatin,
      and blebbing and rupture of the nuclear membrane. This was followed by an
      increase of plasma membrane permeability and cell lysis. During these processes,
      neither apoptotic changes such as nuclear condensation, DNA fragmentation, and
      expression of phospholipid phosphatidylserine on the plasma membrane nor necrotic
      changes such as chromatin clumping and organelle destruction were apparent in the
      treated neutrophils. The fatal effect of the agonist night be specific for
      neutrophils because it failed to promote the rapid death of other types of cells.
      Although activation of neutrophils by ONO-AE-248 was not evident, experiments
      using metabolic inhibitors demonstrated that the agonist caused neutrophil death
      via the activation of protein kinase C in the presence of intracellular ATP.
      These findings indicated that EP3 receptor-mediated signals might promote a novel
      form of neutrophil death, which differs from typical apoptosis or necrosis.

PMID- 10947063
TI  - Effects of theophylline on human eosinophil functions: comparative study with
      neutrophil functions.
AB  - The understanding of theophylline as a bronchodilator has been reconsidered in
      recent years. We undertook to determine its immunomodulatory actions in
      granulocytes and elucidate their mechanism. Preincubation of neutrophils with
      theophylline (10(-5) to 5 x 10(-3) M) had a biphasic effect on O2(-) production
      stimulated with N-formyl-methionyl-leucyl-phenylalanine or C5a. Theophylline
      potentiates O2(-) production via adenosine A(2A) receptor antagonism induced by
      receptor-linked agonists from neutrophils, but not from eosinophils. The addition
      of theophylline caused a significant decline in neutrophil chemotaxis at lower
      concentrations than those for eosinophil motility. Theophylline reduces
      neutrophil chemotaxis via adenosine A1 receptor antagonism. At high
      concentrations, with an intracellular cAMP accumulation as a result of
      phosphodiesterase (PDE) inhibition, theophylline also exerts an inhibitory effect
      on the O2(-) production and chemotaxis of both types of cells. The difference in
      theophylline's effect on neutrophils and eosinophils appears to depend on the
      existence of specific adenosine receptors. Theophylline thus modulates
      granulocyte functions in association with specific adenosine receptor antagonism
      and cAMP-PDE inhibition.

PMID- 10947064
TI  - Trafficking of neutrophils across airway epithelium is dependent upon both
      thioredoxin- and pertussis toxin-sensitive signaling mechanisms.
AB  - Leukocyte recruitment from the circulation into the airways is a multi-step
      process, involving both chemotactic and adhesive mechanisms. Using an in vitro
      model of leukocyte transepithelial trafficking, we show that movement of human
      peripheral blood neutrophils (PMN) across airway epithelium in the optimal
      basolateral-to-apical surface direction is partially blocked by pertussis toxin,
      an inhibitor of G(alphai)-protein-linked receptors. A neutralizing monoclonal
      antibody against interleukin-8 (IL-8; constitutively expressed by airway
      epithelium) did not inhibit PMN transepithelial migration, suggesting that
      alternative pertussis toxin-sensitive signaling mechanisms are involved in this
      process. However, a neutralizing antibody against thioredoxin, a redox enzyme
      with pertussis toxin-insensitive chemoattractant activity, did reduce PMN
      migration across airway epithelium. We conclude that trafficking of PMN across
      airway epithelium is mediated by both thioredoxin- and pertussis toxin-sensitive
      signaling mechanisms that are independent of IL-8.

PMID- 10947065
TI  - Human neutrophil cathepsin G down-regulates LPS-mediated monocyte activation
      through CD14 proteolysis.
AB  - A major property of monocytes/macrophages is to recognize and to be activated by
      bacterial wall components such as LPS, through membrane receptors including the
      key element CD14. We demonstrate that CD14 expression is down-regulated, as
      judged by flow cytometry analysis, upon incubation of human monocytes with
      purified cathepsin G (CG), a releasable neutrophil serine proteinase. The
      progressive decrease of CD14 expression due to increasing concentrations of CG
      highly correlates (P < 0.0001) with the decreased synthesis of tumor necrosis
      factor alpha (TNF-alpha) in response to lipopolysaccharide (LPS). This effect is
      dependent on the enzymatic activity of CG but is not exerted through an
      activation of monocytes. Immunoblot analysis reveals that CD14 (M(r) = 57,000) is
      directly cleaved by CG and released into the extracellular medium as a high-M(r)
      species (M(r) = 54,000). In this context, incubation of monocytes with activated
      neutrophils leads to a down-regulation of CD14 expression, a process blocked by a
      serine proteinase inhibitor. These data suggest a paradoxical anti-inflammatory
      property for CG.

PMID- 10947066
TI  - Evaluation of the expression of NADPH oxidase components during maturation of HL
      60 cells to neutrophil lineage.
AB  - To understand the expression of NADPH oxidase components during neutrophil
      maturation, we examined the expression of mRNAs and proteins for NADPH oxidase
      components, and the superoxide-producing activity using HL-60 cells incubated
      with dimethyl sulfoxide (DMSO). Northern blot and Western blot analyses revealed
      that gp91(phox), p67(phox), and p47(phox) were expressed after myelocyte stages,
      whereas p22(phox), p40(phox), and rac-2 were expressed from the promyelocyte
      stage. Furthermore, immunocytochemical staining of DMSO-induced HL-60 cells
      indicated that gp91(phox), p67(phox), and p47(phox) were detected only after
      myelocyte stages (myelocytes, metamyelocytes, band cells, and segmented cells),
      whereas p22(phox), p40(phox), and rac-2 were detected from the promyelocyte
      stage. In addition, nitro blue tetrazolium (NBT) assay showed that superoxide
      could be produced after myelocyte stages but not produced before promyelocyte
      stages. Moreover, almost the same results as those with DMSO-induced HL-60 cells
      were obtained using human bone-marrow cells by immunocytochemical staining and
      NBT assay, except that p22(phox) was detected by immunocytochemical staining
      after myelocyte stages in bone-marrow cells. Together, these observations
      indicate that all the components for NADPH oxidase are expressed, and the
      superoxide-producing activity is obtained after myelocyte stages during
      neutrophil maturation.

PMID- 10947067
TI  - Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue
      tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic cell death.
AB  - We attempted to induce MUC1-specific cytotoxic T lymphocytes (CTLs) by mixed
      lymphocyte tumor cell culture (MLTC) using two allogeneic MUC1-positive cancer
      cell lines, T-47D and MCF7. The induced CTLs exhibited MUC1-specific cytotoxicity
      16 days after the initial stimulation. However, these CTLs underwent apoptotic
      death within 16 days. To examine whether the B7-1 molecule is required for the
      expansion of the responder cells, a B7-1(+)/MUC1(-) cell line was transfected
      with MUC1 cDNA, and the resulting transfectant was employed as a stimulator in an
      autologous MLTC. The CTLs exhibited MUC1 specificity but also continued to
      propagate. In parallel, autologous dendritic cells (DCs) were added to an MLTC
      containing peripheral blood lymphocytes (PBLs) and the allogeneic MUC1-positive
      stimulators. The CTLs demonstrated MUC1 specificity and their number increased.
      This suggests that the B7-1 molecule is required for rescuing CTLs from MUC1
      mediated apoptotic death, but not for the induction of MUC1-specific
      responsiveness. This strategy to obtain the CTLs efficiently may be useful for
      adoptive immunotherapy against cancer.

PMID- 10947068
TI  - Resting and activated T cells induce expression of E-selectin and VCAM-1 by
      vascular endothelial cells through a contact-dependent but CD40 ligand
      independent mechanism.
AB  - This study explored the effect on endothelial cell (EC) activation of contact
      with T lymphocytes, which occurs during lymphocyte emigration into inflamed
      tissues. Addition of T cells to umbilical vein or dermal microvascular EC
      monolayers stimulated expression of EC E-selectin and VCAM-1. This response
      required direct cell:cell contact, but not T-cell activation. The capacity of
      resting CD4+ T cells to activate EC was restricted to the CD45RO+ subset and
      could be enhanced by 6 h prestimulation of T cells with PMA and ionomycin. The EC
      stimulating capacity of resting or activated T cells was independent of CD40
      ligand. Furthermore, inhibition of TNF-alpha/beta and IL-1alpha/beta, together
      with CD40 ligand, failed to inhibit EC activation by resting T cells and only
      inhibited the response to PMA- and ionomycin-activated T cells by 40 +/- 18%. Our
      data suggest that T-cell-EC interactions can lead to EC activation through a
      novel contact-dependent, but CD40 ligand-independent, mechanism.

PMID- 10947069
TI  - Expression of alpha4-integrins on human neutrophils.
AB  - alpha4 Integrins are important adhesion molecules mediating binding of
      lymphocytes, monocytes, and eosinophils to multiple cellular and extracellular
      ligands. Mature neutrophils have been recently suggested to express alpha4
      integrins as well. We studied whether human neutrophils can synthesize alpha4
      integrins upon activation in vitro or in vivo. Two anti-alpha4 mAbs, but not
      multiple subclass-matched non-binding controls, reacted with granulocytes in an
      inducer and time-dependent manner. Nevertheless, staining with Ig subclass
      specific second-stage reagents surprisingly revealed that commercial anti-alpha4
      mAbs contain two distinct Igs, the alpha4-specific IgG1 and an IgG2a of an
      unknown specificity. We showed that in vitro inductions used by us and others
      only induce the binding of nonspecific IgG2a from the commercial HP2/1 to
      activated neutrophils. By reverse-transcriptase polymerase chain reaction, alpha4
      mRNA was not detectable in purified neutrophils. Our results show that alpha4
      integrin protein and mRNA are absent from normal and stimulated human
      neutrophils.

PMID- 10947070
TI  - Parallel induction of epithelial surface-associated chemokine and proteoglycan by
      cellular hypoxia: implications for neutrophil activation.
AB  - Neutrophil-induced damage to the protective epithelium has been implicated in
      mucosal disorders associated with hypoxia, and such damage may be initiated by
      epithelial-derived chemokines. Because chemokines can bind to membrane
      proteoglycans, we hypothesized that chemokines may associate with epithelial
      surfaces and activate polymorphonuclear neutrophils (PMN). Epithelial hypoxia
      (pO2 20 torr) resulted in a time-dependent induction of interleukin-8 (IL-8)
      mRNA, soluble protein, as well as surface protein. Such surface IL-8 expression
      was demonstrated to be dependent on heparinase III expression, and extensions of
      these experiments indicated that hypoxia induces epithelial perlecan expression
      in parallel with IL-8. Finally, co-incubation of post-hypoxic epithelia with
      human PMN induced IL-8-dependent expression of the PMN beta2-integrin CD11b/18.
      These data indicate that chemokines liberated from epithelia may exist in a
      surface-bound, bioactive form and that hypoxia may regulate proteoglycan
      expression.

PMID- 10947071
TI  - Combined inhibition of indoleamine 2,3-dioxygenase and nitric oxide synthase
      modulates neurotoxin release by interferon-gamma-activated macrophages.
AB  - We evaluated the synthesis of nitric oxide (NO) and of the neurotoxic kynurenine
      metabolites 3OH-kynurenine and quinolinic acid (QUIN) in interferon-gamma (IFN
      gamma)-activated macrophages of the murine BACl.2F5 cell line with the aim of
      investigating the roles of mononuclear phagocytes in inflammatory neurological
      disorders. IFN-gamma induced indoleamine 2,3-dioxygenase (IDO) and NO synthase
      (NOS) and increased the synthesis of 3OH-kynurenine, QUIN, and NO that
      accumulated in the incubation medium where they reached neurotoxic levels.
      Macrophage exposure to norharmane, an IDO inhibitor, resulted in a decreased
      formation of not only the kynurenine metabolites but also NO. The inhibition of
      NO synthesis could not be ascribed to reduced NADPH availability or decreased NOS
      induction. Norharmane inhibited NOS activity also in coronary vascular
      endothelial cells and in isolated aortic rings. Our findings suggest that
      activated macrophages release large amounts of neurotoxic molecules and that
      norharmane may represent a prototype compound to study macrophage involvement in
      inflammatory brain damage.

PMID- 10947072
TI  - Lipopolysaccharide-triggered desensitization of TNF-alpha mRNA expression
      involves lack of phosphorylation of IkappaBalpha in a murine macrophage-like cell
      line, P388D1.
AB  - Activation of nuclear factor kappaB (NF-kappaB) is thought to be required for
      cytokine production by lipopolysaccharide (LPS)-responsive cells. Here, we
      investigated the contribution of NF-kappaB in preventing LPS-induced
      transcription of the tumor necrosis factor alpha (TNF-alpha) gene in a murine
      macrophage cell line, P388D1, when tolerance was induced in the cells with a
      short exposure to a higher dose of LPS. Electrophoretic mobility shift assays
      with the kappaB elements of the murine TNF-alpha promoter and enhancer revealed
      that nuclear mobilization of heterodimers of p65/p50, c-rel/p50 and p65/c-rel,
      and homodimers of p65 was markedly reduced in LPS-tolerant cells, whereas that of
      p50 homodimers was only slightly increased. Western blot analysis showed that the
      phosphorylation of Ser32 on IkappaBalpha and its transient degradation did not
      occur in LPS-tolerant cells. These results thus suggest that desensitization of
      TNF-alpha gene expression in this LPS-tolerant state is closely associated with
      down-regulation of transactivating NF-kappaB and may involve a defect in the LPS
      induced IkappaBalpha kinase pathway.

PMID- 10947073
TI  - TNF-alpha-mediated neutrophil apoptosis involves Ly-GDI, a Rho GTPase regulator.
AB  - We investigated intracellular signaling events involved in fibronectin
      accelerated TNF-alpha-mediated PMN apoptosis by means of 2-D gel electrophoresis
      and western blotting. Proteins were sequenced with electrospray ionization mass
      spectrometry. Apoptosis was quantitated by flow cytometry. We detected a cluster
      of acidic, high molecular-weight proteins that were only tyrosine phosphorylated
      when TNF-alpha-treated PMN interacted with fibronectin. Sequence analysis
      revealed that one of these proteins was Ly-GDI, a regulator of Rho GTPases.
      Fibronectin increased the TNF-alpha-induced Ly-GDI cleavage, yielding a 23-kD
      fragment. At 8 h, intact Ly-GDI was decreased to 33% on fibronectin, compared
      with 69% on PolyHema (P<0.05). Inhibition of tyrosine phosphorylation prevented
      phosphorylation of Ly-GDI, fibronectin-accelerated Ly-GDI cleavage, and
      fibronectin-accelerated apoptosis in TNF-alpha-treated PMN. We found that Ly-GDI
      cleavage was dependent on caspase-3 activation and that caspase-3 inhibition
      decreased apoptosis. We conclude that tyrosine phosphorylation of Ly-GDI,
      followed by increased caspase-3-mediated Ly-GDI cleavage, is a signaling event
      associated with accelerated TNF-alpha-mediated apoptosis on fibronectin.

PMID- 10947074
TI  - Beta2 integrin (CD11/CD18)-mediated signaling involves tyrosine phosphorylation
      of c-Cbl in human neutrophils.

PMID- 10947075
TI  - Chronic PMA treatment of Jurkat T lymphocytes results in decreased protein
      tyrosine phosphorylation and inhibition of CD3- but not Ti-dependent antibody
      triggered Ca2+ signaling.
AB  - We have treated Jurkat T lymphocytes with a concentration (160 nM) of phorbol
      myristyl acetate (PMA) that down-regulates conventional and novel protein kinase
      C (PKC) isozymes and we have investigated the effects on Ca2+ signaling and
      protein tyrosine phosphorylation using mAb (C305) directed against the beta
      subunit of the Ti heterodimer or the epsilon/delta-component of the CD3 complex
      (mAb Leu 4 or OKT 3). The levels of expression of PKC alpha, betaI, betaII, and
      delta were reduced by 90% or more in PMA-treated cells, whereas the expression of
      PKCtheta decreased by approximately 30%. In contrast, the chronic treatment with
      PMA increased the expression of PKCepsilon and PKCzeta. There was a lack of Ca2+
      response and myo-inositol trisphosphate (IP3) production in PMA-treated cells
      when they were exposed to mAb Leu 4 but the cells responded to mAb C305. The
      treatment with PMA did not affect the surface expression of Ti or CD3. The
      overall levels of tyrosine-phosphorylated proteins were markedly reduced in PMA
      treated cells. We investigated whether these observations were related to defects
      in signal transduction related to protein tyrosine kinase (PTK) of the src and
      syk families. The electrophoretic mobilities of p59(fyn) or ZAP-70 were not
      changed in PMA-treated cells but p56(Ick) migrated as a large band of M(r) 60-62
      kDa. The decreased mobility of p56(Ick) was related to a state of
      hyperphosphorylation. The activity of modified p56(Ick) was not up-regulated in
      activated Jurkat cells. Our data suggest that clonotypic Ti can trigger Ca2+
      mobilization independently of conventional PKC isoforms. Our observations further
      suggest that conventional PKC isoforms are involved early in the cascade of
      events associated with Jurkat T lymphocyte activation.

PMID- 10947076
TI  - Evidence for transcriptional self-regulation of variable surface antigens in
      Paramecium tetraurelia.
AB  - Variable surface antigens are commonly found on free-living and parasitic
      protozoa, yet the regulation of antigen expression and switching is not fully
      understood in any system. A cell line of Paramecium tetraurelia stock 51 can
      express at least 11 different antigens yet only one type is found on the surface
      at any one time. Previous studies have shown that mutually exclusive expression
      of Paramecium surface antigens can be overcome if two antigen genes contain the
      same 5' coding region. In this article we utilize a gene chimera containing
      portions of A51 and B51 to analyze the effect of a frameshift mutation on
      transcription and steady-state mRNA levels. We show that a frameshift mutation
      near the 3' end prevents expression of the protein on the cell surface and
      reduces the rate of transcription of the corresponding gene. The difference in
      transcription is not the result of differences in plasmid copy number. We propose
      that expression of the antigen on the cell surface is part of a self-regulatory
      pathway that influences transcription of the corresponding gene. A model
      incorporating the previous and current data is presented.

PMID- 10947077
TI  - Nuclear receptor coactivator SRC-1 interacts with the Q-rich subdomain of the AhR
      and modulates its transactivation potential.
AB  - The aryl hydrocarbon receptor (AhR), a soluble cytosolic protein, mediates many
      of the toxic effects of TCDD and related chemicals. The toxic effects are largely
      cell, tissue, and promoter context dependent. Although many details of the
      overall dioxin signal transduction have been elucidated, the transcriptional
      regulation of dioxin-induced genes like cyp1A1 is not yet completely understood.
      Previously, we have shown that the co-regulator RIP140 is a potential AhR
      coactivator. In this report, the role of coactivator, SRC-1, in AhR-mediated
      transcriptional regulation was examined. SRC-1 increased AhR-mediated, TCDD
      dependent reporter gene activity three-fold in Hepa-1 and COS-1 cells. In in
      vitro interaction assays, SRC-1 was found to interact with AhR but not with ARNT.
      SRC-1 interacted weakly with AhR in the absence of TCDD and the addition of
      ligand further increased SRC-1 binding to AhR. Deletional mapping studies of the
      AhR revealed that SRC-1 binds to the AhR transactivation domain. Finer mapping of
      the SRC-1-interacting subdomains in the AhR transactivation domain suggested that
      the Q-rich subdomain was necessary and sufficient for interaction, similar to
      that seen with RIP140. Using GFP-tagged constructs, SRC-1 was shown to interact
      with AhR in cells. Unlike RIP140, LXXLL motifs in SRC-1 were necessary for
      interaction with AhR in vitro and for coactivation in Hepa-1 cells. The
      recruitment of certain coactivators by a variety of receptors suggests possible
      common coactivator pools and competition among receptors for limiting
      coactivators. Examination of the role of SRC-1 in AhR/ARNT transactivation in
      ARNT-deficient mutant Hepa-1 c4 cells demonstrates that the AhR transactivation
      domain is sufficient for enhanced coactivation mediated by SRC-1 in the presence
      of a transactivation domain deleted ARNT protein.

PMID- 10947078
TI  - Effect of adenovirus E1A on ICAM-1 promoter activity in human alveolar and
      bronchial epithelial cells.
AB  - In previous studies we demonstrated that the E1A DNA and proteins of group C
      adenovirus are present in excess in the lungs of patients with chronic
      obstructive pulmonary disease (COPD). Because adenovirus EIA gene products are
      known to regulate the expression of many genes by interacting with cellular
      transcription factors, we postulated that E1A enhances the production of
      inflammatory mediators and exacerbates the inflammatory process in smokers'
      lungs. We reported that LPS-induced ICAM-1 expression in A549 cells is
      upregulated by E1A. In the current study we investigated whether this regulation
      is mediated through the ICAM-1 promoter. A549 cells and primary human bronchial
      epithelial (HBE) cells were transiently cotransfected with a plasmid containing
      the ICAM-1 enhancer-promoter linked to the chloramphenicol acetyltransferase
      (CAT) reporter gene (pBS-CAT-P) and either a plasmid carrying the adenovirus 5
      E1A gene (pE1Aneo) or a control plasmid (pneo). To compare the effect of
      transient versus stable E1A expression on the activity of this promoter, we also
      transiently transfected stable E1A-expressing A549 cells with pBS-CAT-P.
      Transient cotransfection of pE1Aneo and pBS-CAT-P had no effect on basal ICAM-1
      promoter activity in A549 or HBE cells. After stimulation of A549 cells with TNF
      alpha, IFN-gamma, or LPS, promoter activity was increased by two- to threefold in
      the presence of adenovirus EIA. In HBE cells, on the other hand, E1A repressed
      the ICAM-1 promoter after stimulation with IFN-gamma and LPS with little change
      after TNF-alpha stimulation. In stable E1A transfectants, ICAM-1 promoter
      activity was 2 to 2.5 times higher than in control transfectants with or without
      stimulation with TNF-alpha or LPS. These findings suggest that EIA can modulate
      the activity of the ICAM-1 promoter in lung epithelial cells and this modulation
      is different in cells of alveolar origin compared to bronchial epithelial cells.

PMID- 10947079
TI  - Effect of intercistronic length on internal ribosome entry site (IRES) efficiency
      in bicistronic mRNA.
AB  - Specific structures found in the mRNA of picornavirus are known to allow a cap
      independent translation. These structures, named internal ribosome entry sites
      (IRES), are also able to favor translation of the second cistron in bicistronic
      mRNAs. Their mechanism of action is not well understood. In the present study,
      two IRESs have been used: the IRES from poliovirus and a newly discovered IRES
      (SUR) composed of the 5' P untranslated sequence from SV40 early genes, the R
      structure, and a small part of the U5 region from the human leukemia virus-1
      (HTLV-1). The bicistronic constructs containing the firefly luciferase gene as
      the first cistron and the chloramphenicol acetyltransferase (CAT) as the second
      cistron were driven by the Rous sarcoma virus (RSV) promoter and contained the
      early gene SV40 terminator. All the resulting plasmids were tested by
      transfection in HeLa and CHO cells. In the bicistronic mRNAs without IRES, the
      expression of the CAT gene was dependent on the distance between the two
      cistrons. The maximum efficiency in the expression of the second cistron was
      obtained when the intercalating RNA was composed of 30 to 90 nucleotides. This
      expression was deeply reduced when the intercalating fragment contained 8 or 300
      nucleotides and was undetectable with 500 nucleotides. Unexpectedly, the
      luciferase mRNA was almost not expressed when the intercalating RNA was of 8 or
      30 nucleotides. Expression of the luciferase gene occurred when the
      intercistronic RNA fragment was of 80 nucleotides and it became lower at 300 and
      500 nucleotides. The same observations were done when the poliovirus or the SUR
      IRESs were added after the intercistronic spacers. However, expression of the CAT
      gene was amplified by both IRESs. When the CAT cistron preceded by the poliovirus
      or SUR IRES was introduced within luciferase cistron, 316 nucleotides before its
      termination codon, the IRESs were able to initiate translation of the following
      CAT gene irrespectively of the mRNA luciferase reading frame. Moreover, with all
      these constructs the highest expression level of the CAT cistron did not exceed
      10% of that obtained with the same vector carrying only the CAT cistron. To
      identify a possible relation between the IRESs and the cap site, the CAT cistron
      preceded or not with an IRES was introduced 210 nucleotides downstream of the AUG
      codon of the luciferase gene (i.e., 258 nucleotides from the cap site) and 100
      nucleotides after an added UAG termination codon. Expression of the CAT gene was
      not modified by the addition of the poliovirus IRES but it was strongly
      stimulated by the SUR IRES (the level of expression corresponded to 65% of that
      obtained with the same vector carrying only the CAT cistron). These results
      suggest that there is a cooperation between the cap and the SUR IRES and not the
      poliovirus IRES to stimulate translation. These data indicate that IRESs must be
      introduced in precise position to allow an efficient expression of the second
      cistron in bicistronic mRNAs.

PMID- 10947080
TI  - Glucocorticoids differentially inhibit expression of the RET proto-oncogene.
AB  - The RET proto-oncogene encodes a receptor tyrosine kinase activated by the
      binding of factors from the glial cell line-derived neurotrophic factor (GDNF)
      family to receptor-alpha components such as GDNF family receptor alpha-1 (GFR
      alpha-1). Mutations within the sequence of the RET proto-oncogene are associated
      with multiple endocrine neoplasia type 2 (MEN 2), an inherited tumor syndrome
      characterized by the development of medullary thyroid carcinoma (MTC) and other
      neuroendocrine tumors. Despite Northern analysis showing that RET is expressed in
      the majority of MTCs, the factors regulating this expression are poorly
      understood. To address this issue we examined RET expression in response to
      glucocorticoids in the TT cell line, derived from a metastatic MTC. The synthetic
      glucocorticoid dexamethasone was found to reduce RET expression at both mRNA and
      protein levels. This effect was dose responsive and maximal at 24 h. The
      reduction in RET mRNA was shown to be specific to glucocorticoids and was also
      seen in a primary MTC culture. Nuclear run-on studies revealed the reduction in
      steady-state RNA to be due to a decrease in RET mRNA transcription and the effect
      was shown to be independent of new protein synthesis or RNA stability.
      Dexamethasone was also found to exert an inhibitory effect upon cell growth,
      suggesting a potential use for glucocorticoids in the treatment of medullary
      carcinoma and MEN 2.

PMID- 10947083
TI  - Effect of consumption of potato chip scraps on the performance of pigs.
AB  - A two-phase study was conducted to determine the effect of potato chip scraps
      (PCS) consumption on dry matter intake (DMI), average daily gain (ADG), and gain:
      feed ratio (G:F) of nursery (Phase 1) and growing-finishing (Phase 2) pigs as
      well as carcass characteristics of the finished pigs. In Phase 1 (42 d), pigs (n
      = 138, avg BW 6.31 +/- .12 kg) were stratified by sex and weight and used in a
      randomized complete block design with three treatments in four blocks. Each
      treatment consisted of four pens of 11 or 12 pigs each. In Treatment 1 (control),
      pigs were fed a corn and soybean meal-based diet supplemented to meet NRC
      requirements. In Treatments 2 and 3, on an as-is basis, 15% and 20% of the corn,
      respectively, were replaced with 15% and 20% of PCS. Substitution of different
      levels of PCS for corn had no effect (P = .23) on the ADG of nursery pigs.
      However, DMI was reduced (P = .01) and G:F was improved (P = .004) linearly as
      the level of PCS in the diets was increased. In Phase 2, nursery pigs from Phase
      1 were combined and continued on their respective treatments to study the effect
      of level of PCS consumption on the performance of growing and finishing pigs and
      carcass characteristics of finished pigs. In this phase, each treatment consisted
      of two pens of 22 to 24 pigs. Increasing the level of PCS resulted in a linear
      decrease (P = .07) in DMI and ADG (P = .001). However, G:F was linearly increased
      (P = .002) with increasing level of PCS in the diet. Increasing the level of PCS
      in the diets resulted in a linear decrease (P = .023) in the dressing percentage
      of the pigs. No other carcass characteristics or organoleptic effects were noted
      due to the PCS substitution in the diet of these pigs. This experiment
      demonstrates that PCS at the levels used in this study can be an effective
      substitute for corn in the diet of nursery and growing and finishing pigs.

PMID- 10947084
TI  - The influence of suckling interval on milk production of sows.
AB  - The objective of this study was to determine whether sow milk yield per gland
      could be increased by reducing the interval between suckles (suckling interval).
      Eighteen sows were allocated at their first farrowing to three treatments
      comprising litter sizes of 6 or 12 piglets or a cross-suckling treatment that was
      imposed to increase suckling frequency. The cross-suckled treatment comprised two
      groups of six piglets each. Each suckling group was allowed to suckle the sow
      during 30-min intervals each day between d 6 and d 28 of lactation. The suckling
      interval was shorter (P < .05) for cross-suckled sows than for sows suckling
      single litters of 6 or 12 piglets during early lactation (d 10 to 14) and late
      lactation (d 24 to 28). Average piglet growth rate between birth and 28 d of age
      was greatest (P < .05) for piglets in the single litters of six and lowest for
      piglets in the cross-suckled treatments. Single litters of 12 piglets had the
      highest (P < .05) litter growth rates, followed by the cross-suckled litters and
      then the single litters of six piglets. The concentration of lactose and fat in
      milk from sows remained relatively stable, although milk from the cross-suckled
      sows contained more protein in early lactation (P < .05). Milk yield of sows was
      not significantly increased (P > .05) by the cross-suckle treatment, although
      during early lactation, milk yield tended to be greater from sows in the cross
      suckle treatment than from sows suckling single litters of six (8,920 g/d vs
      7,819 g/d, P < .1). The concentration of DNA and total RNA and the RNA:DNA ratio
      in mammary glands was unaffected by treatment (P > .05). Sows with single litters
      of 12 piglets had the greatest total DNA in their udders (P < .05). However,
      individual gland weights were heavier (P < .05) in cross-suckled sows than in
      sows with single litters of 6 or 12 piglets. Increased suckling frequency seemed
      to play a role in increased mammary gland weight and milk production during
      lactation.

PMID- 10947081
TI  - Metastatic conversion of chemically transformed human cells.
AB  - A linear model for human cell metastasis has been developed in vitro from
      chemically transformed normal human cells. The chemically transformed cells are
      nontumorigenic in nude mice, but can be converted to a tumorigenic phenotype by
      transfection with a nondirectional cDNA library or antisense cDNA to the ML-1
      gene. The primary transfected cell line (TR1T) forms localized, progressively
      growing tumors in nude mice that do not invade into the surrounding tissue. This
      tumorigenic TR1T cell line could be advanced into a metastatic stage following an
      additional transfection (TR2M cell line) with the cDNA expression library or
      antisense cDNA to the ML-1 gene. Metastatic cells, selected from tumors that were
      attached to internal organs, exhibited an increase in invasiveness as measured in
      vitro using an invasion chamber. The metastatic cells also exhibited an increased
      expression of matrix metalloproteinase-1 (MMP-1), although MMP-1 was not part of
      the cDNA that was transfected into either the TR1T cells or the doubly
      transfected metastatic TR2M cells. These data suggest that the increase in MMP-1
      expression was a secondary downstream event responding to an upstream genetic
      change that initiated the conversion of cells from a tumorigenic to a metastatic
      stage. In summary, human cell lines representing premalignant, malignant, and
      metastatic phenotypes have been established in culture that can be used to
      identify gene changes that occur as normal human cells progress to a metastatic
      stage during tumor development. One gene, ML-1, that is found in the expression
      library appears to be involved in malignant progression, because ML-1 antisense
      cDNA will convert chemically transformed cells to both tumorigenic and metastatic
      stages, and cells from both local and metastatic tumors have a reduced or
      complete loss of expression of the ML-1 gene.

PMID- 10947082
TI  - Genetic alterations in the transforming growth factor receptor complex in
      sporadic endometrial carcinoma.
AB  - Cellular responses to the transforming growth factor beta (TGFbeta) ligand,
      including inhibition of cell proliferation, are mediated by a heteromeric
      receptor complex composed of TGFbeta types I and II receptors (TbetaR-I and
      TbetaR-II). Loss of responsiveness to TGFbeta, attributed to inactivation of the
      TbetaR complex, has been implicated in the development of tumors in a number of
      human epithelial and lymphoid tissues. To gain a better understanding of TGFbeta
      signal transduction pathways in endometrial carcinogenesis, we have investigated
      the role of the TbetaR complex by evaluating the TbetaR-I and TbetaR-II genes for
      mutations throughout the entire coding region in human sporadic endometrial
      tumors. Using reverse transcription-PCR, "Cold" single-strand conformation
      polymorphism analysis, and direct DNA sequencing, it was found that 1 of 39
      (2.6%) and 7 of 42 samples (17%) contained code-altering changes in the kinase
      domain of TbetaR-I and TbetaR-II, respectively. In 7betaR-I, a 3-bp deletion was
      found resulting in replacement of Arg and Glu at codon 237 and 238 by Lys. With
      TbetaR-II, mutations were found in the kinase, the extracellular, and the C
      terminal domains. No frameshift mutations were detected; however, a silent
      population polymorphism (AAC-->AAT at codon 389) in TbetaR-II was found in 19 of
      42 (44%) tumor samples. These results suggest that alteration in TbetaR-II, but
      not TbetaR-I, has an important role in the development of endometrial carcinoma.

PMID- 10947085
TI  - Effects of planting density and processing method on laboratory characteristics
      of grain sorghum for ruminants.
AB  - Grain sorghum grown in 38-cm (high-density) or 76-cm rows (normal-density) was
      steam-flaked, harvested as high-moisture grain followed by rolling and ensiling,
      or dry-rolled. Chemical composition, enzymatic starch availability, CP
      insolubility, and IVDMD in a reduced-strength buffer were evaluated. High-density
      planting increased (P < .10) OM and starch concentration and decreased (P <
      .0001) CP concentration but did not affect (P > .10) P concentration, enzymatic
      starch availability, or CP insolubility. High-density planting resulted in lower
      (P < .10) in vitro ruminal culture pH at 6, 12, and 18 h of incubation when grain
      sorghum was processed by steam flaking, and lower (P < .10) IVDMD at 6, 12, and
      18 h of digestion when grain sorghum was processed by dry rolling. Steam flaking
      decreased (P < .10) CP concentration and solubility and increased (P < .10) OM
      concentration. High-moisture ensiling decreased (P < .10) the insolubility of CP
      but did not otherwise seem to alter the chemical composition of grain sorghum
      relative to dry rolling. Starch was more available (P < .10), and DM was digested
      more rapidly and extensively (P < .10) in vitro, in steam-flaked sorghum followed
      by high-moisture sorghum. Based on these data, it seems that planting density
      primarily affected chemical composition of grain sorghum, whereas processing
      primarily affected CP insolubility and rate and extent of starch fermentation.

PMID- 10947086
TI  - Chemical characteristics and relative bioavailability of supplemental organic
      zinc sources for poultry and ruminants.
AB  - Eight commercially available organic Zn products and reagent-grade ZnSO4 x 7H2O
      (Zn Sulf) were evaluated by polarographic analysis, and solubility in .1 M K2HPO4
      KH2PO4 buffer (pH 5), .2 M HCl-KCl buffer (pH 2), and deionized water. Fractions
      from these solubility tests were evaluated by gel filtration chromatography for
      structural integrity. Degree of chelation was generally positively related to
      chelation effectiveness determined by polarography. The organic sources were Zn
      methionine complex A (Zn MetA), Zn methionine complex B (Zn MetB), Zn
      polysaccharide complex (Zn Poly), Zn lysine complex (Zn Lys), Zn amino acid
      chelate (Zn AA), Zn proteinate A (Zn ProA), Zn proteinate B (Zn ProB), and Zn
      proteinate C (Zn ProC). Three experiments were conducted to estimate the relative
      bioavailability of Zn from the organic Zn supplements for chicks and lambs when
      added at high dietary levels to practical diets. Bone Zn concentration increased
      (P < .001) as dietary Zn increased in both experiments. When Zn Sulf was assigned
      a value of 100% as the standard, multiple linear regression slope ratios of bone
      Zn from chicks fed 3 wk regressed on dietary Zn intake gave estimated relative
      bioavailability values of 83 +/- 14.6 and 139 +/- 16.9 for Zn AA and Zn ProA,
      respectively, in Exp. 1 and 94 +/- 11.6, 99 +/- 8.8, and 108 +/- 11.4 for Zn
      Poly, Zn ProB, and Zn ProC, respectively, in Exp. 2. In Exp. 3, 42 lambs were fed
      diets containing Zn Sulf, Zn ProA, Zn AA, or Zn MetB for 21 d. Based on multiple
      linear regression slope ratios of liver, kidney, and pancreas Zn and liver
      metallothionein concentrations on added dietary Zn, bioavailability estimates
      relative to 100% for Zn Sulf were 130, 110, and 113 for Zn ProA, Zn AA, and Zn
      MetB, respectively. Except for Zn ProA, which was greater, the organic Zn
      supplements had bioavailability values similar to that of Zn Sulf for chicks and
      lambs. Bioavailability of organic Zn products was inversely related to solubility
      of Zn in pH 5 buffer in chicks (r2 = .91) and pH 2 buffer in lambs (r2 = .91),
      but not to an estimate of degree of chelation.

PMID- 10947087
TI  - Using serial ultrasound measures to generate models of marbling and backfat
      thickness changes in feedlot cattle.
AB  - Serial ultrasound estimates of backfat thickness and marbling score were obtained
      on two groups of steers fed high-energy rations for averages of 166 and 148 d.
      These measurements were used to develop mathematical models that described the
      changes in those two attributes as functions of days on feed. An exponential
      model best described the increase in backfat thickness, and the rate coefficients
      were .0117 and .0096 for the two groups (doubling times = 59 and 72 d,
      respectively). A modified power function was better than either a linear or
      exponential model for describing the development of marbling. In this model,
      marbling increased very slowly, approximately one degree every 100 d, in the
      interval from low Select to low Choice but then increased at faster rates as
      initial marbling scores became higher. Ultrasound backfat measures could be used
      to predict days to reach a target carcass backfat level with an average error of
      30 d or less when backfat thickness averaged more than 3 mm at evaluation.
      Projections from measurements taken when cattle were started on feed were not
      accurate from one group, which averaged only 1.7 mm backfat at that time.
      Projections of carcass marbling improved as evaluation date neared slaughter
      date. Projections from the initial evaluation date allowed tentative
      categorization of candidates for Choice or not Choice but were only 64% accurate.
      Projections from evaluations made later in the feeding period exceeded 75%
      accuracy in distinguishing Choice from Select. Only small relationships (r2 = .07
      or .16) existed between carcass backfat thickness and marbling score. Results
      indicate that ultrasound estimates of backfat and marbling made during the
      feeding period can be used to predict carcass merit at slaughter.

PMID- 10947088
TI  - Group size and floor-space allowance can affect weanling-pig performance.
AB  - Crossbred weanling piglets (n = 1,920; mean initial BW, 5.3 +/- .7 kg) were used
      in two 9-wk trials employing a randomized block design in a 2 x 2 factorial
      arrangement of treatments to determine effects of group size (20 [Small = S] or
      100 [Large = L] pigs/pen) and floor-space allowance (calculated requirement [CR]
      or calculated requirement less 50% of estimated "free space" [CR-50]) on growth
      performance. Free space was estimated for each group size. From wk 1 through 4
      after weaning, S and L groups at CR were allowed a floor space of .17 m2/pig, and
      at CR-50, S and L groups were allowed .15 m2/pig and .13 m2/pig, respectively.
      From wk 5 through 9 after weaning, all CR treatment pigs were provided a floor
      space of .38 m2/pig, and for the CR-50 treatment, S and L pigs were allowed .32
      m2/pig and .28 m2/pig, respectively. Piglets had free access to feed and water.
      Feeder-trough space per pig was the same for both group sizes. Feed-intake data
      were collected for only wk 1 through 4. Group size by floor-space allowance
      interactions (P < .05) were found for gain/feed ratio (G/F) for wk 1 and wk 2
      through 4, but not for wk 1 through 4. Piglets in L groups were lighter (P <
      .001) at the end of wk 1, 4, and 9 by 2, 4, and 5%, respectively, and had lower
      ADG (6%; P < .001) throughout the trial than S piglets. During wk 1 through 4,
      feed intake was lower (7%, P < .001) in L piglets than in S piglets, but G/F was
      similar (P > .05). Piglets in CR groups had greater ADG (5%; P < .01) throughout
      the trial, with a greater G/F (P < .05) for wk 1 through 4, and were heavier (P <
      .01) than those in CR-50 groups at the end of wk 4 (3%) and 9 (4%). Pigs in L
      groups had a greater within-pen coefficient of variation in BW at the end of wk 9
      than pigs in S groups. Large groups and reduced floor-space allowance reduced
      piglet growth performance in the nursery.

PMID- 10947089
TI  - Hormonal therapy for sows weaned during fall and winter.
AB  - Sows from five commercial herds were weaned in the fall and winter and used to
      ascertain the potential application of hormonal therapy to stimulate subsequent
      litter size born. At weaning sows within parity (1, 2, and 3 through 6) and
      lactation length classification (early weaned, < or = 14 d; conventionally
      weaned, > 14 d) were randomly assigned to treatment. Treatments were injection
      with P.G. 600 (400 IU PMSG with 200 IU hCG) at weaning or no treatment. Sows were
      individually observed for estrus and mated following protocol for each herd.
      Breeding, culling, and farrowing data were collected. Treatment with P.G. 600 did
      not change subsequent rebreeding performance for sows at parity 1 or parities 3
      through 6. However, conventionally weaned parity-2 sows treated with P.G. 600
      were more likely (P < .05) to return to estrus than conventionally weaned
      controls (99.0 vs 93.6%, respectively). For parity-1 and parity-2 sows, treatment
      did not significantly change the likelihood for farrow percentage. However, the
      likelihood to farrow a litter was greater (P < .05) among P.G. 600-treated sows
      at parities 3 to 6 that were conventionally weaned (84.4 vs 71.3%, respectively).
      Subsequent litter birth weight for parity-1 sows treated with P.G. 600 was lower
      (P < .02) than for controls (15.6 vs 16.6 kg, respectively). Subsequent litter
      size at birth was not affected by treatment for parity-1 or parity-2 sows
      compared with controls. However, early-weaned sows at parities 3 through 6
      treated with P.G. 600 had more (P < .06) total number born than controls (12.4 vs
      10.6, respectively). Treatment with P.G. 600 improved reproductive function
      within specific parity and lactation length classification for sows weaned in the
      fall and winter.

PMID- 10947090
TI  - Interaction of dietary magnesium level on the feeding value of supplemental fat
      in finishing diets for feedlot steers.
AB  - A feeding trial involving 160 crossbred steers (357 kg) and a metabolism trial
      involving eight Holstein steers (189 kg) cannulated in the rumen and proximal
      duodenum were conducted to evaluate the interaction of dietary Mg level (.18 vs
      .32%, DM basis) and supplemental fat (0% supplemental fat vs 4% tallow [T],
      yellow grease [YG], or griddle grease [GG]) on growth performance and NE value of
      the diet. Dietary Mg level did not influence (P > .10) growth performance. Daily
      weight gain was lower (11%, P < .05) for steers fed GG than for those fed YG.
      Supplemental fat decreased (5%, P < .10) DMI and increased (P < .05) gain
      efficiency (7%). There was a fat x Mg level interaction (P < .01) for dietary NE.
      The increase in dietary NEg with T and YG supplementation was similar (8.6 vs
      8.0%) for diets containing .18 and .32% Mg. In contrast, the increase in dietary
      NEg with GG supplementation was 8.9% with .18% dietary Mg, but the NEg value of
      the diet did not increase when GG was added to diets with .32% dietary Mg.
      Dressing percentage was lower (1.5%, P < .1) and retail yield was greater (2.2%,
      P < .05) for steers fed GG- than for steers fed YG-supplemented diets. Increasing
      dietary Mg level increased kidney, pelvic, and heart fat (5.5%, P < .05). There
      was a fat x Mg level interaction (P < .1) for marbling score. With diets
      containing no supplemental fat, increasing dietary Mg decreased (15.2%) the
      marbling score, and with diets containing supplemental fat, increasing dietary Mg
      increased (7.2%) the marbling score. Fat supplementation decreased (P < .01)
      ruminal and total tract digestion of OM (10 and 3.5%, respectively) and NDF (37
      and 17%, respectively). Supplemental fat did not affect (P > .10) Ca digestion
      but decreased (41.7%, P < .01) apparent Mg digestion. Increasing dietary Mg level
      increased (77.7%, P < .05) apparent Mg digestion. There were no treatment effects
      (P > .10) on postruminal fatty acid digestion. Fat supplementation decreased
      (17.3%, P < .01) the acetate:propionate molar ratio. Total ruminal protozoal
      counts were increased (12.7%, P < .05) by increasing dietary Mg level and
      decreased (12.9%, P < .05) by fat supplementation. We conclude that supplemental
      fats may depress Mg absorption. Increasing dietary magnesium levels beyond
      current recommendations may increase marbling scores in cattle fed fat
      supplemented diets but may not affect growth performance or dietary NE. The NE
      value of fat is a predictable function of level of fat intake.

PMID- 10947091
TI  - The effect of time of artificial insemination on fertilization status and embryo
      quality in superovulated cows.
AB  - Thirty nonlactating Holstein cows were superovulated to determine the effect of
      artificial insemination time on fertilization status and embryo quality. During
      the luteal phase of the estrous cycle, cows were administered 38 mg FSH-P in a 4
      d descending dose regimen. Luteolysis was induced with two injections of
      prostaglandin on the last day of FSH-P treatment. All cows were continuously
      monitored for behavioral estrus using the HeatWatch estrus detection system. All
      cows were inseminated once with one .5-mL straw (50 x 10(6) sperm) at either 0 (n
      = 10), 12 (n = 10), or 24 h (n = 10) after the first standing event. The elapsed
      time (mean +/- SD) from the first prostaglandin dose to the first standing event
      was 39.4 h +/- 7.7 h. The (mean +/- SD) duration of behavioral estrus was 13.2 h
      +/- 4.1 h. The (mean +/- SD) number of standing events was 27 +/- 17. Five
      hundred twenty-nine embryos and ova were recovered nonsurgically 6 d after
      insemination. Fertilization rates were 29 (0 h), 60 (12 h), and 81% (24 h) (P <
      .01). Percentages of excellent and good, fair and poor, and degenerate embryos
      were not different (P > .05). Percentages of embryos with accessory sperm were 5
      (0 h), 8 (12 h), and 41 (24 h) and differed between the 0 and 24 h and the 12 and
      24 h inseminations (P < .01). Artificial insemination of superovulated,
      nonlactating Holstein cattle 24 h after onset of estrus increased fertilization
      rate and percentage of embryos with accessory sperm compared with insemination at
      0 or 12 h after onset of estrus. Embryo quality was not affected by time of
      insemination.

PMID- 10947092
TI  - Parameter estimates for number of lambs born at different ages and for 18-month
      body weight of Rambouillet sheep.
AB  - Genetic parameters were estimated using REML with animal models for number of
      lambs born and 18-mo body weight in Rambouillet sheep. Number of lambs born was
      modeled either as repeated measurements on the same trait or as different traits
      at different ages. The original data for number of lambs born were separated
      according to age of the ewe into two classes: 2 and 3 yr, and older than 3 yr.
      Numbers of ewes with lambing records for the age classes were 653 and 466 with
      1,106 and 1,118 records, respectively. For the data set that included all ages,
      the number of ewes was 684 with 2,224 records, and for 18-mo body weight the
      number of ewes measured was 557. For number of lambs born, the animal model
      included random genetic, permanent environmental, and residual environmental
      effects and fixed effects for age of ewe, year of lambing, and month of year of
      lambing. Lambing day within season was used as a covariate. For 18-mo body
      weight, year of birth of ewe was used as a fixed effect. Actual age in days when
      the ewe was weighed was used as a covariate. Estimates of heritability for number
      of lambs born by age group were .04, for 2- and 3-yr old ewes, and .06, for ewes
      greater than 3 yr old, from the two-trait (two age of ewe classes) analyses and
      .06 when all ages were included. Estimates of heritability for number of lambs
      born from the single-trait analyses were somewhat less than estimates from two
      trait analyses. Estimate of genetic correlation between number of lambs born for
      the 2 and 3 yr and the >3 yr classes was near unity (1.00), which suggests that a
      repeated measures model for number of lambs born is adequate for making selection
      decisions. Estimate of genetic correlation between number of lambs born and 18-mo
      body weight was .35 with a heritability estimate of .48 for 18-mo body weight.
      The estimate of genetic correlation suggests that selection for increased number
      of lambs born would result in increased 18-mo body weight.

PMID- 10947093
TI  - Additive genetic parameter estimates for heifer pregnancy and subsequent
      reproduction in Angus females.
AB  - A primary objective of this study was to determine whether the binary traits
      heifer pregnancy (HP) and subsequent rebreeding (SR) were heritable in an
      experimental population of Angus cattle. A second objective was to determine the
      nature of the additive genetic relationships among HP, SR, and stayability
      (S(5/1)) in the same population. Heifer pregnancy was defined as the observation
      of a heifer conceiving and remaining pregnant to palpation at 120 d, given
      exposure during the breeding season. Subsequent rebreeding was defined as the
      observation of a 2-yr-old conceiving and remaining pregnant to palpation at 105
      d, given pregnancy as a yearling and exposure during the breeding season.
      Stayability was defined as the probability of a female having at least five
      calves, given she becomes a dam as a 2 yr old. Data were analyzed using a maximum
      a posteriori probit threshold model to predict breeding values on the liability
      scale and Method R procedures to estimate variance components in the
      determination of heritability (h2). Additive genetic groups were used in
      determining the additive genetic relationships among these fertility traits.
      Additive genetic groups were formed on one trait's breeding values and used in
      the prediction of another trait's breeding values. Analyses yielded h2 estimates
      that were out of the parameter space 8.5 and 46.3% for HP and SR, respectively,
      and 5.9% for the reestimation of S(5/1). The majority of point estimates outside
      the parameter space for SR converged toward 0, whereas those for HP and S(5/1)
      primarily converged toward 1. From the subsamples producing h2 estimates within
      the parameter space, average h2 for HP, SR, and S(5/1) were .21, .19, and .15,
      with standard deviations of .12, .14, and .08, respectively. The estimates of h2
      indicate that HP and S(5/1) were heritable and should respond favorably to
      selection; however, SR did not appear heritable due to the large number of
      subsamples producing h2 estimates out of the parameter space. Fixed effect
      estimates for age of dam were significant for HP. From the analyses using
      additive genetic groups, the relationship among HP and S(5/1) appeared to be
      nonlinear. This potential nonlinear relationship seen between HP and S(5/1)
      indicates that selection for improved female fertility would be most effective by
      having predictions on both traits.

PMID- 10947094
TI  - Decreased growth in angus steers with a short TG-microsatellite allele in the P1
      promoter of the growth hormone receptor gene.
AB  - A polymorphic TG-repeat microsatellite is located 90 base pairs upstream from a
      major transcription start site in the bovine growth hormone receptor gene. A
      shorter allele with 11 consecutive TG is common in Bos indicus cattle, whereas
      longer 16- to 20-TG-repeat alleles predominate in Bos taurus breeds. The purpose
      of this study was to compare growth and carcass traits between Angus steers that
      had two of the longer growth hormone receptor alleles with their half-siblings
      that had one short allele and one of the longer alleles. We genotyped 64 Angus
      sires with respect to the poly-TG microsatellite and identified six bulls that
      were heterozygous in that they had one short 11-TG allele and one of the longer
      alleles. We then grouped 125 steer progeny of these six heterozygous bulls
      according to their genotypes: only the longer 16- to 20-TG-repeat alleles were
      found in 73 steer progeny (long/long homozygotes), whereas a short 11-TG allele
      was paired with one of the longer alleles in 52 progeny (short/long
      heterozygotes). Contrasts for the long/long homozygotes vs the short/long
      heterozygotes were significant for weaning weight (17 +/- 4 kg; P < .001) and
      carcass weight (14 +/- 5 kg; P < .01). Approaching significance (P = .03) was the
      contrast for USDA marbling score (-.3 +/- .2). No significant differences (P >
      .05) were detected for contrasts in birth weight (.3 +/- .6 kg), longissimus
      muscle area (-.2 +/- 1 cm2), or carcass fat depth (-.01 +/- .07 cm). This
      polymorphism has potential for use in DNA marker-assisted selection programs.

PMID- 10947095
TI  - Technical note: Constrained optimization of breed composition in composite
      populations to balance net merit and risk.
AB  - We developed a method to derive optimum composite genotypes when the proportion
      of a specific breed (or combination of breeds) in the composite is constrained to
      a desired level. The method allows development of composites that balance net
      merit according to available parameters and reflects the production system
      and(or) risk preference, particularly when traits in the breeding objective do
      not represent all traits important for production. The method can also be used to
      evaluate the cost of constraining breed use. For example, when the true optimal
      composite is difficult to obtain in the time frame available to the producer, the
      predicted merit of the composite with breed proportion restricted to those that
      are obtainable in practice can be compared with the predicted merit of the true
      optimum composite. In a case study the method is used to optimize a tropical
      composite using Brahman, Charolais, and Belmont Red breeds. The proportion of
      Charolais is to be constrained to 50%. Using growth parameters from a tropical
      crossbreeding experiment, the unconstrained optimum composite was 32.5% Brahman,
      11.1% Belmont Red, and 56.3% Charolais. When the proportion of Charolais in the
      composite was constrained to 50%, optimum proportions of Brahman and Belmont Red
      were 33.9% and 16.1% respectively. In the case study net merit (annualized profit
      per cow exposed, $), as defined by the growth parameters, was .2% less than that
      of the unconstrained optimum composite.

PMID- 10947096
TI  - Parameter estimates for greasy fleece weight of Rambouillet sheep at different
      ages.
AB  - Variance components for greasy fleece weight in Rambouillet sheep were estimated.
      Greasy fleece weight was modeled either as repeated measurements on the same
      trait or as different traits at different ages. The original data were separated
      according to the age of the ewe at shearing into three classes; 1 yr, 2 and 3 yr,
      and older than 3 yr. An animal model was used to obtain estimates of genetic
      parameters with a REML algorithm. Total numbers of animals in pedigrees for the
      different age classes were 696, 729, and 573, respectively, and 822 for the
      repeated measures model across ages. The animal model included direct genetic,
      permanent environmental, and residual environmental random effects and fixed
      effects for age of ewe, shearing date as contemporary group, and number of lambs
      born. Days between shearings was used as a covariate. Single-trait analyses were
      initially done to obtain starting values for multiple-trait analyses. A repeated
      measures model across ages was also used. Estimates of heritability by age group
      were .42, .50, and .58 from three-trait (age class) analyses and for the repeated
      measures model the estimate was .57. Estimates of genetic correlations between
      fleece yields for 1 yr and 2 and 3 yr, 1 yr and >3 yr, and 2 and 3 yr and >3 yr
      classes were .88, .89, and .97, respectively. These estimates of genetic
      correlations suggest that a repeated measures model for greasy fleece weight is
      adequate for making selection decisions.

PMID- 10947097
TI  - Genetic analysis of litter size in Targhee, Suffolk, and Polypay sheep.
AB  - Data on litter size, weaning weights at 60, 90, and 120 d, postweaning gains from
      weaning to 120 or 365 d of age, fleece weight, and fiber diameter from Targhee,
      Suffolk, and Polypay flocks participating in the U.S. National Sheep Improvement
      Program were used to estimate genetic parameters for litter size and genetic
      relationships between early-life traits and future litter size. Records on 7,591
      lambings by 3,131 Targhee ewes, 10,295 lambings by 5,038 Suffolk ewes, and 6,061
      lambings by 2,709 Polypay ewes were used. Heritability estimates for litter size
      ranged from .09 to .11 across breeds; repeatability ranged from .09 to .13.
      Additive genetic effects on litter size were generally positively, and
      occasionally significantly, correlated with animal additive genetic effects on
      weaning weights and postweaning gains. Genetic correlations (r(a)) ranged from
      .08 to .48 in Targhee and from .17 to .43 in Suffolk but were close to 0 in
      Polypay (-.14 to .09). Additive maternal effects on weaning weight were
      positively associated with litter size in Suffolk and Polypay; this correlation
      was negative (-.23 to -.35), but not significant, in Targhee. Fleece weight was
      not strongly associated with litter size; (r(a) = -.09 to .21). However, fiber
      diameter had a significant undesirable correlation with litter size (.30) in
      Targhee. Estimates of phenotypic correlations of litter size with early-life
      traits were uniformly small (-.02 to .08). Thus, although occasional genetic
      antagonisms between litter size and early-life traits were observed in these
      data, none appeared large enough to prevent simultaneous genetic improvement in
      both traits.

PMID- 10947098
TI  - Investigation of genotype x environment interactions for weaning weight for
      Herefords in three countries.
AB  - The objective of this study was to investigate the possibility of genotype x
      environment interactions for weaning weight (WWT) between different regions of
      the United States (US) and between Canada (CA), Uruguay (UY), and US for
      populations of Hereford cattle. Original data were composed of 487,661, 102,986,
      and 2,322,722 edited weaning weight records from CA, UY, and US, respectively. A
      total of 359 sires were identified as having progeny across all three countries;
      240 of them had at least one progeny with a record in each environment. The data
      sets within each country were reduced by retaining records from herds with more
      than 500 WWT records, with an average contemporary group size of greater than
      nine animals, and that contained WWT records from progeny or maternal grand
      progeny of the across-country sires. Data sets within each country were further
      reduced by randomly selecting among remaining herds. Four regions within US were
      defined: Upper Plains (UP), Cornbelt (CB), South (S), and Gulf Coast (GC).
      Similar sampling criteria and common international sires were used to form the
      within-US regional data sets. A pairwise analysis was done between countries and
      regions within US (UP-CB vs S-GC, UP vs CB, and S vs GC) for the estimation of
      (co)variance components and genetic correlation between environments. An
      accelerated EM-REML algorithm and a multiple-trait animal model that considered
      WWT as a different trait in each environment were used to estimate parameters in
      each pairwise analysis. Direct and maternal (in parentheses) estimated genetic
      correlations for CA vs UY, CA vs US, US vs UY, UP-CB vs S-GC, UP vs CB, and S vs
      GC were .88 (.84), .86 (.82), .90 (.85), .88 (.87), .88 (.84), and .87 (.85),
      respectively. The general absence of genotype x country interactions observed in
      this study, together with a prior study that showed the similarity of genetic and
      environmental parameters across the three countries, strongly indicates that a
      joint WWT genetic evaluation for Hereford cattle could be conducted using a model
      that treated the information from CA, UY, and US as a single population using
      single population-wide genetic parameters.

PMID- 10947100
TI  - Effect of magnesium mica on performance and carcass quality of growing-finishing
      swine.
AB  - A total of 240 crossbred pigs were used in two experiments to determine the
      effect of feeding magnesium mica (MM) during the growing-finishing period on
      animal performance and pork carcass characteristics. All pigs were blocked by
      weight, and treatments were assigned randomly to pens (five pigs/pen) within
      blocks. In each experiment, eight pens were allotted randomly to one of three
      treatments: 1) a negative control corn-soybean meal starter, grower, and finisher
      diet devoid of supplemental magnesium; 2) the control diets supplemented with
      1.25% MM; and 3) the control diets supplemented with 2.50% MM. In Exp. 1, pigs
      were slaughtered at the University of Arkansas Red Meat Abattoir, whereas pigs in
      Exp. 2 were transported to a commercial pork packing plant and slaughtered
      according to industry-accepted procedures. In both experiments, dietary
      supplementation of MM had no (P > .10) effect on ADG, ADFI, or gain:feed ratio at
      any phase during the growing-finishing period. In Exp. 1, MM supplementation had
      no (P > .10) effect on carcass fatness or muscling. Moreover, Japanese color
      scores were not (P > .10) affected by feeding pigs MM; however, American color
      scores increased linearly (P < .01) with increasing levels of MM in the diet.
      Although MM supplementation did not (P > .10) affect L* and b* values for the
      longissimus muscle (LM), there was a linear increase (P < .05) in LM a* and
      chroma values associated with increased MM levels in swine diets. In Exp. 2,
      carcasses from pigs fed 1.25% MM had less (P < .05) fat opposite the LM at the
      10th rib than untreated controls and pigs fed 2.50% MM and higher (P < .10)
      percentages of muscle than carcasses of untreated controls. Moreover, the LM from
      pigs fed 1.25% MM was less (P < .05) red and less (P < .05) yellow than the LM
      from pigs fed the control or 2.50% MM-supplemented diets. Drip loss from the LM
      was unaffected (P > .10) by inclusion of MM in the diet. Results from this study
      confirm that inclusion of MM, an inexpensive, inorganic magnesium source, in
      diets of growing-finishing swine has beneficial effects on pork carcass
      cutability and quality with no deleterious effects on live animal performance.

PMID- 10947099
TI  - Expression of porcine transcription factors and genes related to fatty acid
      metabolism in different tissues and genetic populations.
AB  - Several transcription factors are involved in regulating lipid metabolism in
      various tissues of animals. Adipocyte determination and differentiation-dependent
      factor 1 (ADD1), peroxisome proliferator activated receptor alpha (PPAR alpha),
      and peroxisome proliferator activated receptor gamma (PPAR gamma) regulate both
      lipogenesis and fatty acid oxidation. We determined the tissue distribution and
      genetic difference in mRNA concentrations of these transcription factors in two
      genetic populations of pigs (Newsham XL-sired Newsham Landrace x Large White
      Duroc and Duroc-sired US Yorkshire x Duroc-Landrace). We also determined the
      tissue distribution and genetic difference in the mRNA concentration of fatty
      acid synthase (FAS) and acyl-CoA oxidase (ACO). Our data showed that ADD1 was
      highly expressed in adipose tissue and liver and that mRNA concentrations of ADD1
      were similar between the two genotypes. The PPAR alpha mRNA concentration was
      high in adipose tissue and was similar between the two genotypes. In both
      populations, PPAR gamma mRNA was detected only in adipose tissue. There was no
      difference between the two genotypes in PPAR gamma mRNA concentration. The ACO
      mRNA was expressed in adipose tissue, skeletal muscle, and liver with no
      difference between genotypes. The FAS mRNA concentration in adipose tissue was
      seven times higher than that in the liver. There was no detectable FAS mRNA in
      skeletal muscle. These data support the concept that pig adipose tissue has
      considerable capability for fatty acid oxidation and synthesis. The uniqueness of
      expression patterns for FAS and ADD1 mRNA further indicates that adipose tissue
      is significantly involved in fatty acid and triacylglycerol synthesis in pigs.

PMID- 10947101
TI  - Nutritional value of a genetically improved high-lysine, high-oil corn for young
      pigs.
AB  - Two experiments were conducted to compare the nutritional adequacy of a
      genetically improved high-lysine, high-oil corn (HLHOC; .408% lysine, 6.21% fat,
      as-fed basis) and a high-oil corn (HOC; .289% lysine, 5.97% fat, as-fed basis)
      for young growing pigs. Experiment 1 used four non-littermate barrows (initially
      20.0 kg BW) fitted with ileal T-cannulas in a crossover-designed digestion study.
      The .75% total lysine diets contained 8.5% casein and an equal amount of lysine
      (.25%) from the test corn. Apparent ileal digestibilities of amino acids, GE, DM,
      and CP were similar (P > .10) between diets. Apparent ileal lysine
      digestibilities were 65 and 71% for the HOC and HLHOC, respectively, assuming the
      lysine in casein to be 100% digestible. Experiment 2 used 100 barrows reared in a
      segregated early-weaning environment (initially 8.3 kg BW and 27 d of age) to
      evaluate five corn-soybean meal-based diets in a 2 x 2 factorial arrangement with
      main effects being corn type and dietary lysine (.80 or 1.15% digestible lysine).
      The fifth diet consisted of the .80% digestible lysine HOC diet supplemented with
      .23% additional L-lysine x HCl (.975% digestible lysine) to verify that lysine
      was the limiting amino acid in the low-lysine diets. Increasing digestible lysine
      from .80 to 1.15% increased (P < .001) ADG and gain/feed (G/F) regardless of corn
      variety. Combined ADG and G/F were .347 kg and .641 and .443 kg and .790 for the
      .80 and 1.15% digestible lysine diets, respectively. Within lysine level, corn
      type did not affect ADG, ADFI, or G/F (P > .10). The results of these studies
      indicate that the lysine in HLHOC is as available as the lysine in HOC and that
      HLHOC can be used successfully in swine diets.

PMID- 10947102
TI  - Limiting order of amino acids and the effects of phytase on protein quality in
      corn gluten meal fed to young chicks.
AB  - An amino acid deletion assay, a protein efficiency ratio (PER) assay, and a slope
      ratio growth assay were used to establish the limiting order of AA, and to
      determine the effects of microbial phytase on protein utilization in corn gluten
      meal (CGM) fed to chicks during the period of 8 to 21 d posthatching. In Assay 1,
      a 12% CP CGM diet was fortified with AA to fulfill the digestible AA ideal
      profile (only Phe + Tyr, Leu, and Pro exceeded requirements) for young chicks.
      Amino acids were then individually deleted, and all diets were fortified to 23%
      CP, with Glu varying as necessary. A Met-fortified 23% CP corn-soybean meal diet
      served as a positive control. No weight gain or feed efficiency differences were
      observed between the fully fortified CGM basal diet and the corn-soybean meal
      positive-control diet. The limiting order of AA established in CGM was 1) Lys, 2)
      Trp, 3) Arg, 4) Thr, 5) Val, 6) Ile, 7) His, 8) cystine, and 9) Met. In Assay 2,
      diets with 10% CP furnished by CGM or casein were fed in the presence and absence
      of 1,200 U/kg phytase. A protein source x phytase interaction (P < 0.05) was
      observed for weight gain, gain:feed, and PER, indicating positive responses to
      phytase when casein was fed but negative responses to phytase when CGM was fed.
      In Assay 3, graded levels of protein (8, 16, and 24% CP) furnished by CGM were
      fed in the presence and absence of 1,200 U/kg phytase. Weight gain and gain:feed
      increased linearly (P < 0.05) as a function of protein intake, but phytase
      supplementation had no effect on weight gain or gain:feed slopes. These results
      indicate that 1,200 U/kg phytase did not increase either CP or AA utilization in
      CGM for young chicks.

PMID- 10947103
TI  - Sporidesmin-induced mortality and histological lesions in mouse lines divergently
      selected for response to toxins in endophyte-infected fescue.
AB  - For eight generations, mouse lines were selected for smaller or larger reduction
      in postweaning gain from endophyte-infected fescue seed in the diet. After five
      generations in which there was no further selection for divergence in response to
      fescue toxicosis, the current experiment was conducted to determine whether
      resistant (R) and susceptible (S) lines differed in response to the mycotoxin
      sporidesmin (SPD). At approximately 8 wk of age, R and S mice that had never
      consumed endophyte-infected fescue seed were randomly assigned (five to seven per
      line x sex x SPD dose subclass) to receive dimethyl sulfoxide (DMSO) carrier or
      10, 20, 30, or 40 mg/kg SPD by oral gavage. At death or euthanasia 14 d after
      treatment, livers and kidneys were collected for histological examination. Mice
      receiving 40 mg/kg SPD died sooner than mice receiving 30 mg/kg (63 vs 134 h; P =
      .02), but there was no line or line x dose interaction effect for time to death.
      Within those mice, neither line, dose, nor their interaction influenced liver
      weight or liver weight as a proportion of body weight. The R mice were more
      resistant to SPD than S mice; LD50 values were 23.6 and 31.8 mg/kg for the S and
      R lines, respectively (P < .05). Sporidesmin caused dose-related liver and kidney
      lesions in both lines. Selection lines did not differ significantly in the
      incidence of infarcts of hepatic lobules. However, at 30 and 40 mg/kg SPD doses,
      severity of this lesion was higher in affected S than in affected R mice. At the
      higher SPD doses, there also was a greater incidence of hepatic subacute
      cholangitis in S mice than in R mice. Foci of acute tubular necrosis were found
      in kidneys of mice receiving 20, 30, or 40 mg/kg SPD, with no protection against
      these lesions in the R line. Foci of tubular basophilia (indicative of tubular
      regeneration) were present in all line x dose subgroups, but incidence was not
      SPD dose-dependent in either line. In summary, divergent selection for weight
      gain response to ingestion of endophyte-infected fescue seed resulted in a
      favorable correlated response in survival following exposure to a chemically
      distinct toxin. It may be possible therefore, to select livestock populations for
      simultaneous resistance to a variety of toxins.

PMID- 10947104
TI  - Administration of recombinant bovine tumor necrosis factor-alpha affects
      intermediary metabolism and insulin and growth hormone secretion in dairy
      heifers.
AB  - Four experiments were conducted to clarify the effect of intravenous (i.v.)
      administration of recombinant bovine tumor necrosis factor alpha (rbTNF) on
      selected metabolites and on hormone secretion in Holstein heifers (n = 6; 347.0
      kg average BW). In Exp. 1, rbTNF was injected at three dosage levels in a Latin
      square; 0 (CONT), 2.5 (TNF2.5), or 5.0 (TNF5) microg/kg BW. Plasma glucose and
      triglyceride concentrations were at first elevated (P < .05) by rbTNF treatment
      and then were decreased (P < .05) by TNF2.5 and TNF5. Plasma NEFA concentrations
      were increased (P < .05) in rbTNF-treated groups. The injection of rbTNF resulted
      in an increase in plasma insulin levels (P < .05 with TNF5) during the period
      between 2 and 24 h, except for the period between 6 and 8 h, after the treatment.
      In Exp. 2, 3, and 4, each heifer received i.v. injections of glucose (.625 mM/kg
      BW) + rbTNF (5 microg/kg) or glucose + saline (10 mL) (Exp. 2), insulin (0.2
      U/kg) + rbTNF or insulin + saline (Exp. 3), and GHRH (0.25 microg/kg) + rbTNF or
      GHRH + saline (Exp. 4) at 1-wk intervals. In Exp. 2, rbTNF inhibited (P < .05)
      glucose-stimulated insulin secretion during the initial phase. Thereafter, plasma
      insulin was higher (P < .01) with the glucose + rbTNF treatment than with the
      glucose + saline treatment. Treatment with rbTNF inhibited the insulin-stimulated
      glucose utilization (Exp. 3) and GHRH-stimulated GH secretion (Exp. 4) during the
      initial phase. These results suggest that rbTNF directly and(or) indirectly
      affects the intermediary metabolism and hormone secretion in Holstein heifers.

PMID- 10947106
TI  - Preparation of an epithelium-free mammary fat pad and subsequent mammogenesis in
      ewes.
AB  - The objective of this study was to develop a surgical procedure for the
      preparation of an epithelium-free mammary fat pad (cleared mammary fat pad; CFP)
      in ewes. At 7 to 10 d of age, ewe lambs (n = 43, mean BW 9.2 +/- .2 kg at 14 d)
      were sedated and one mammary gland was locally anesthetized. An incision
      circumscribing the base of the teat was made and blunt dissection was performed
      through the extraneous mammary fat pad tissue to enable the parenchyma and teat
      to be wholly removed. Failure to completely remove the epithelium enabled it to
      regenerate and grow into the mammary fat pad. Mean diameter of the parenchymal
      rudiment at 7 to 10 d of age was 8.9 +/- .5 mm (range of 5 to 16 mm). The
      excision site was closed with wound clips and recovered lambs returned to their
      dams. The contralateral mammary gland remained intact, allowing it to undergo
      normal development. Live weight gain was unaffected by this procedure. Ewes were
      subsequently slaughtered in groups at various stages of prepuberty, puberty,
      gestation, and lactation. Of 39 operated glands recovered, only one demonstrated
      epithelial outgrowth within the CFP. Parenchyma within the contralateral, intact
      gland underwent phases of rapid growth in prepuberty, puberty, and late gestation
      and was capable of milk synthesis after steroid induction or parturition. Change
      in weight of the CFP paralleled that of the intact mammary gland to 100 d of
      pregnancy. Sham CFP surgery was performed on four additional ewes wherein the
      parenchyma was completely excised and immediately replaced. Sham-operated
      epithelium populated the mammary fat pad and synthesized milk that could be
      expressed from the teat. A CFP in sheep will be a useful model for future
      investigations into the local growth regulatory mechanisms associated with
      ruminant mammogenesis.

PMID- 10947105
TI  - Effect of the previously gravid uterine horn and postpartum interval on
      follicular diameter and conception rate in beef cows treated with estradiol
      benzoate and progesterone.
AB  - An experiment was performed to evaluate the effect of the side of ovulation with
      respect to the previously gravid uterine horn on fertility of cows inseminated at
      one of two periods postpartum. All cows were treated with an intravaginal
      progesterone insert for 7 d and received estradiol benzoate (2 mg, i.m.) at the
      time of device insertion, prostaglandin F2alpha (25 mg, i.m.) at the time of
      device removal, and estradiol benzoate (1 mg, i.m.) 30 h after device removal.
      All cows were inseminated 28 to 30 h after the second treatment with estradiol
      benzoate, regardless of observed estrus. Cows treated in Period 1 received
      inserts at 16 to 20 d postpartum and were inseminated at 25 to 29 d postpartum.
      Cows treated in Period 2 received inserts at 26 to 30 d postpartum and were
      inseminated at 35 to 39 d postpartum. Diameter of the largest follicle at insert
      removal was greater in cows treated in Period 2 (10.1 +/- 0.3; mm +/- SEM) than
      in cows treated in Period 1 (9.1 +/- 0.3; P < .05). Diameter did not differ with
      the side of ovulation in respect to the previously gravid uterine horn. Diameter
      was greater in cows 5 to 9 (10.3 +/- 0.3) than in cows 3 to 4 (9.0 +/- 0.3) or 10
      to 13 (9.4 +/- 0.6) yr of age (P < .01). The proportion of cows that ovulated
      from the ovary contralateral to the previously gravid uterine horn was greater (P
      < .05) than of those that ovulated from the ipsilateral ovary, and the incidence
      of ovulation was reduced in cows 3 to 4 yr of age (P < .01). Conception rate
      tended to be greater for ovulation from the ipsilateral compared with the
      contralateral ovary, relative to the previously gravid uterine horn (P < .10) and
      for ovulation from the right than the left ovary (P < .06). Conception rate was
      less if cows ovulated a follicle that was < 9 mm than a follicle > or = 9 mm in
      diameter at insert removal (P < .01) and was greater in cows inseminated in June
      than in April or May (P < .05). In conclusion, in cows in which estrus was
      synchronized at 25 to 39 d postpartum, ovulation from either the ovary
      ipsilateral to the previously gravid uterine horn, or the right ovary, tended to
      increase fertility.

PMID- 10947107
TI  - Development of an estrus synchronization protocol for beef cattle with short-term
      feeding of melengestrol acetate: 7-11 synch.
AB  - An estrus synchronization protocol (7-11 Synch) was developed to synchronize the
      first follicular wave and timing of ovulation in postpartum beef cows. In Exp. 1,
      follicular development and timing of ovulation in response to the following
      protocol were evaluated. Beef heifers (n = 12) and cows (n = 6), at random stages
      of the estrous cycle, were fed melengestrol acetate (MGA; .5 mg x animal(-1) x d(
      1)) for 7 d and injected with PGF2alpha (PG; 25 mg) on the last day of MGA. A
      second injection of PG was administered 11 d after cessation of MGA. After the
      second injection of PG, estrus was synchronized in 6/12 heifers and 3/6 cows. The
      interval to estrus in heifers and cows was 54 and 64 h, respectively (P > .10).
      All animals exhibiting estrus ovulated first-wave follicles. Animals that failed
      to respond to the second injection of PG were in estrus later than 6 d after
      cessation of MGA and had corpora lutea that were unresponsive to the injection of
      PG. Based on the variation in interval to estrus following the first PG injection
      on the last day of MGA feeding in Exp. 1, an injection of GnRH (100 microg) was
      added to the protocol 4 d after the cessation of MGA to ensure ovulation or
      luteinization of dominant follicles and synchronization of first-wave follicular
      development. This revised protocol was termed "7-11 Synch." In Exp. 2, two estrus
      synchronization protocols were compared. Multiparous beef cows were stratified by
      breed and postpartum interval and randomly assigned to the 7-11 Synch (n = 44) or
      Select Synch protocols (GnRH injection followed by PG injection 7 d later; n =
      45). Timing of estrus after the last PG injection (0 h) ranged from 42 to 102 h
      in the 7-11 Synch group and -30 to 114 h in the Select Synch group. Eight cows
      (18%) in the Select Synch group exhibited estrus 30 h before to 18 h after PG.
      Synchronized estrus peaked between 42 and 66 h after the last PG injection, and a
      maximum number of cows were in estrus at 54 h for both treatment groups.
      Synchrony of estrus from 42 to 66 h was greater (P < .05) in 7-11 Synch (91%:
      41/44) than in Select Synch cows (69%: 31/45). Artificial insemination pregnancy
      rate from 42 to 66 h was greater (P < .05) in the 7-11 Synch group (66%: 29/44)
      than in the Select Synch group (40%: 18/45). In summary, the 7-11 Synch protocol
      improved synchrony of estrus without reducing fertility. This protocol has
      potential future application for fixed-time AI in beef cattle production systems.

PMID- 10947108
TI  - Grazing methods and stocking rates for direct-seeded alfalfa pastures: I. Plant
      productivity and animal performance.
AB  - A 4-yr study was conducted to determine the effects of two grazing methods (GM)
      at two stocking rates (SR) on alfalfa pasture plant productivity and animal
      performance and to ascertain the effect of grazing systems on subsequent
      performance of steers fed a high-concentrate diet. Eight pasture plots (.76 ha)
      were seeded in 1988 with alfalfa (Medicago sativa L. var. WL225) and divided into
      two blocks of four pastures each. Grazing methods consisted of a traditional four
      paddock or an intensive 13-paddock system. Pastures were managed to allow a 36-d
      rest period with an average grazing season of 110 d. The low and high SR were 5.9
      vs 11.7, 5.3 vs 10.5, 5.3 vs 7.9, and 5.3 vs 7.9 steers/ha for years 1989 to
      1992, respectively. Following the grazing season, steers were placed in a feedlot
      and fed a high-concentrate diet (81% high-moisture corn, 14% corn silage, 5%
      protein-mineral supplement) for an average of 211 d. There was no effect of GM on
      herbage mass, pasture phase ADG, or live weight gain/hectare. Increasing the
      number of paddocks was beneficial when herbage mass was limited and stocking rate
      was above 7.9 steers/ha. Increasing SR above 7.9 steers/ha decreased herbage mass
      and pasture-phase ADG. As forage allowance increased, pasture-phase ADG increased
      quadratically (R2 = .82, P < .001), reached a plateau, and then decreased.
      Previous grazing system did not influence the performance of steers in the
      feedlot or their carcass characteristics. Optimum SR is dependent on herbage mass
      produced.

PMID- 10947109
TI  - Grazing methods and stocking rates for direct-seeded alfalfa pastures: II.
      Pasture quality and diet selection.
AB  - A 2-yr study was conducted to determine the effects of two grazing methods (GM)
      and two stocking rates (SR) on alfalfa (Medicago sativa L. var. WL225) pasture
      quality and diet selection by Holstein steers. Eight pasture plots (.76 ha) were
      seeded in 1988 and divided into two blocks of four pastures each. Pastures were
      managed to allow a 36-d rest period with an average grazing season of 105 d.
      Before steers entered the next paddock, canopy heights (CH) of alfalfa plants
      were determined and pasture-forage samples were collected. Forage samples were
      analyzed for DM, OM, CP, and in vitro OM digestibility (IVOMD). At 12-d intervals
      beginning with the second grazing cycle, extrusa samples were collected from
      steers with esophageal fistulas. Extrusa samples were frozen, freeze-dried, and
      analyzed for OM, CP, IVOMD, in situ ruminal DM degradation, and ruminal
      undegradable protein. There were no effects of GM on alfalfa CH or pasture DM,
      OM, CP, and IVOMD. Increasing the SR increased pasture CP content in both years
      and increased DM, OM, and IVOMD in the 2nd yr. There was no effect of GM or SR on
      the quality of forage selected by esophageally fistulated steers. Esophageally
      fistulated steers selected forage that had greater OM, CP, and IVOMD than the
      average nutrient content of the forage. Although forage quality was greater when
      stocking rates were increased, the quantity of forage available per animal may
      have limited gains.

PMID- 10947110
TI  - Grazing methods and stocking rates for direct-seeded alfalfa pastures: III.
      Economics of alternative stocking rates for alfalfa pastures.
AB  - A framework that permits estimation of economically optimal stocking rates for
      alternative economic parameters and alfalfa forage allowance was developed and
      applied to a controlled grazing experiment conducted with Holstein steers (243
      kg) placed on direct-seeded alfalfa pastures in central Michigan. Responses of
      ADG to alternative levels of forage allowance (FA) were summarized by a quadratic
      function and the associated gains/hectare were calculated. The standard stocking
      rate (SSR; standard livestock units/ha) that maximized gain/hectare increased
      with FA and was greater than that which maximized ADG. Net returns to fixed
      resources(NRFR)/hectare were calculated for alternative SSR and economically
      optimal SSR were identified under various levels of herbage mass (kg/d). The SSR
      that maximized NRFR were between the SSR that maximized ADG and gain/hectare.
      Magnitude of the sale price discount for heavier calves, the slide, influenced
      the optimal SSR and the sensitivity of net return to SSR. The economically
      optimal SSR increased as the slide increased because animals stocked under higher
      SSR weighed less off pasture and therefore received a lower price discount.

PMID- 10947111
TI  - Influence of feed intake fluctuation and frequency of feeding on nutrient
      digestion, digesta kinetics, and ruminal fermentation profiles in limit-fed
      steers.
AB  - Nine crossbred beef steers (344 +/- 26 kg) fitted with ruminal cannulas were used
      in a randomized complete block design to evaluate the effects of feeding
      frequency and feed intake fluctuation on total tract digestion, digesta kinetics,
      and ruminal fermentation profiles in limit-fed steers. In Period 1, steers were
      allotted randomly to one of four dietary treatments: 1) feed offered once daily
      at 0800; 2) feed offered once daily at 0800 with a 10% fluctuation in day-to-day
      feed intake; 3) feed offered twice daily at 0800 and 1700; and 4) feed offered
      twice daily at 0800 and 1700 with a 10% fluctuation in a day-to-day feed intake.
      In Period 2, steers were reallocated across treatments. The 90% concentrate diet
      was fed at 90% of the ad-libitum consumption by each steer. Chromium-EDTA and Yb
      labeled steam-flaked corn were intraruminally infused at 0800 on d 1 and 3 and Co
      EDTA and Er-labeled steam-flaked corn were infused on d 2 and 4 of the 4-d
      collection period. Ruminal samples were collected at 0, 3, 6, 9, 12, 15, 18, and
      24 h after the 0800 feeding, and total feces were collected for 4 d. Total tract
      digestibilities of OM, N, and starch were lowest (fluctuation x frequency, P <
      .05) when feed was offered twice daily with a 10% fluctuation in intake. Ruminal
      fluid volume and passage rate were not affected (P > .10) by feeding frequency or
      intake fluctuation. A frequency x fluctuation x sampling time interaction
      occurred (P < .01) for ruminal pH. Steers fed a constant amount of feed once
      daily had higher (P < .05) ruminal pH at 0, 3, 18, and 24 h than steers fed once
      daily with a 10% fluctuation in feed intake. Total VFA concentration was greater
      (P < .01) at 9 h after the 0800 feeding when feed was offered once vs twice
      daily. Feeding twice daily increased (P < .05) the molar proportion of acetate
      and decreased (P < .05) the molar proportion of propionate. Increasing feeding
      frequency resulted in a more stable ruminal environment; however, the increased
      acetate:propionate ratio with twice-daily feeding might result in lower
      efficiency of energy utilization by limit-fed steers.

PMID- 10947112
TI  - Portal-drained visceral metabolism of 3-hydroxybutyrate in sheep.
AB  - The present experiment was conducted to study the impact of portal-drained
      visceral (PDV) metabolism of arterial 3-OH-butyrate on estimates of the portal
      recovery of intraruminally infused butyrate. Three multicatheterized and rumen
      fistulated Leicester ewes were subjected to three intraruminal infusion protocols
      in a Latin square design: control (C; water), butyrate (B; 20 mmol x h(-1)), and
      butyrate (20 mmol x h(-1)) + propionate (40 mmol x h(-1)) (BP). During the
      experiments, the sheep were infused with 1,2,3,4-13C4-D-3-OH-butyrate in a
      mesenteric vein. Portal recoveries of intraruminally infused butyrate and
      propionate were obtained by comparing Treatments B and BP, respectively, with
      Treatment C. The portal net appearance of butyrate and the portal net appearance
      of butyrate + 3-OH-butyrate accounted for 20 +/- 2% and 48 +/- 14% of
      intraruminally infused butyrate, respectively. Metabolism by the PDV tissues
      accounted for 32 to 44% of the whole-body irreversible loss rate of 3-OH-butyrate
      (12.0 to 24.7 +/- 0.5 mmol x h(-1)). The portal net appearance of butyrate plus
      the unidirectional PDV output of 3-OH-butyrate accounted for 62 +/- 5% of the
      intraruminally infused butyrate, and this estimate was comparable to the portal
      recovery of intraruminally infused propionate (62 +/- 7%). The results from the
      present study show that the extent of epithelial butyrate oxidation is
      overestimated and the portal recovery of butyrate carbon underestimated if only
      portal net appearance rates of butyrate and 3-OH-butyrate are considered.

PMID- 10947113
TI  - Rapid communication: Single nucleotide polymorphisms detected in exon 10 of the
      bovine growth hormone receptor gene.

PMID- 10947114
TI  - Rapid communication: Mapping of nine bovine microsatellite markers obtained from
      large insert genomic libraries.

PMID- 10947116
TI  - Evidence for the expression of radiation-induced potentially lethal damage being
      a p53-dependent process.
AB  - PURPOSE: To test the hypothesis that the expression of potentially lethal damage
      (PLD) is a p53-dependent process. MATERIALS AND METHODS: Previously reported data
      on radiation sensitivity, DNA double-strand break rejoining, PLD expression and
      repair (PLDR) were analyzed for a group of 12 human tumor cell lines and three
      human diploid fibroblast cell lines. Seven of these cell lines had normal p53
      gene expression while the other eight were functionally p53-deficient. None of
      the cell lines was sensitive to radiation-induced apoptosis. RESULTS: Cell lines
      with a normal p53 expression were more sensitive to radiation, but only when
      sensitivity was measured in plateau-phase cultures under conditions where PLDR
      was minimized. Mutation or functional inactivation of p53 by HPV E6
      transformation led to a more radioresistant phenotype under these conditions as
      well as a significant reduction in PLDR. PLDR was inversely proportional to the
      percentage of radiation-induced DNA double-strand breaks rejoined in 1 h in the
      p53 normal cell lines. CONCLUSIONS: These results suggest that the expression of
      PLD is primarily a p53-dependent process. In the absence of functional p53 gene
      expression, the effects of PLD are minimized. These observations help clarify the
      role of p53 in tumor response to radiation therapy because they suggest that the
      effects of alterations in p53 are highly dependent on the microenvironment of the
      tumor, i.e. whether conditions allow for PLDR.

PMID- 10947115
TI  - Defective radiation signal transduction in ataxia-telangiectasia cells.
AB  - PURPOSE: The product of the gene ATM mutated in the human genetic disorder ataxia
      telangiectasia (A-T) is predominantly present in the nucleus Compatible with a
      role in DNA-damage recognition and cell-cycle control. However, ATM is also
      present outside the nucleus in cytoplasmic and membrane associated vesicles,
      which may explain the more general signalling defect in A-T. This led us to
      investigate signalling events initiated by ionizing radiation, remote from the
      nucleus. MATERIALS AND METHODS: A-T and control lymphoblastoid cells were
      employed to study radiation-induced signalling at the level of protein activation
      using immunoprecipitation and immunoblotting. Flow cytometry was used to
      determine mobilization of intracellular Ca2+. RESULTS: Lymphoblastoid cells from
      A-T patients were found to be defective in the radiation-induced activation of
      protein tyrosine kinase p53/p56lyn. In control cells Ca2+ was mobilized in
      response to gamma-radiation largely from internal stores, and increased
      significantly over a 20 min period. This mobilization of Ca2+ was either absent
      or increased very slowly in A-T cells post-irradiation. The same pattern of
      release was observed after treatment with the radiometric agent, streptonigrin.
      In addition the phospatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin
      suppressed the release of Ca2+. CONCLUSION: These data demonstrate that ionizing
      radiation activates lyn kinase and leads to the release of Ca2+, and-for the
      first time-that these steps are ATM-dependent.

PMID- 10947117
TI  - Radiation-induced transcription factor activation in the rat cerebral cortex.
AB  - PURPOSE: To determine the effects of ionising radiation on the DNA-binding
      activity of the injury-related transcription factors AP-1, Sp-1, p53 and NFkappaB
      in the rat brain. MATERIALS AND METHODS: Male Sprague-Dawley rats were irradiated
      with 137Cs gamma-rays at 3.8Gy/min and the cerebral cortex was isolated at
      intervals up to 24h. Nuclear protein extract of the cerebral cortex was analysed
      by electrophoretic mobility shift assay for DNA-binding activity of AP-1, Sp-1,
      p53 and NFkappaB. In addition, total RNA was extracted from the cerebral cortex
      and subjected to northern analysis. RESULTS: The DNA-binding activity of each of
      the transcription factors increased in a time- and dose-dependent manner after
      irradiation. Maximum increase in the activity of AP-1, Sp-1, and p53 DNA binding
      was seen after exposure to 10Gy and then decreased after higher doses. In
      contrast, NFkappaB DNA-binding activity continued to increase out to at least
      30Gy. The levels of bFGF and p21WAF-1 mRNA increased after irradiation,
      suggesting an increase in the transactivating activity of AP-1, Sp-1, and p53.
      CONCLUSIONS: These data indicate that the response of the CNS to irradiation
      includes the activation of a similar set of transcription factors as previously
      observed after other types of insults.

PMID- 10947118
TI  - Loss of wild-type p53 function is responsible for upregulated homologous
      recombination in immortal rodent fibroblasts.
AB  - PURPOSE: A correlation between mutations in the tumour suppressor gene p53 and
      high rates of homologous recombination were previously found in immortal rodent
      fibroblasts. In the current study, direct evidence was sought that loss of p53
      function is mainly responsible for upregulated levels of homologous
      recombination. MATERIALS AND METHODS: Homologous recombination was assessed in
      vitro using DNA plasmid substrates that stably integrated into the genome of
      mouse and rat embryonic fibroblasts. RESULTS: Primary fibroblasts with wild-type
      p53 displayed a recombination rate of about 1 x 10(-4). This number increased by
      33- to 93-fold after spontaneous cellular immortalization, accompanied by loss of
      p53 function. To exclude potential bias from other gene mutations, wild-type p53
      was experimentally disrupted in primary fibroblasts leading to an increase in
      recombination by one order of magnitude. Conversely, re-introduction of wild-type
      p53 into p53-null immortal cells reconstituted suppressed recombination rates.
      Finally, early-passage fibroblast cultures from p53-knock-out mice showed
      elevated recombination rates, which did not increase further following
      immortalization. CONCLUSIONS: Loss of wild-type p53 is the major genetic
      determinant of increased homologous recombination frequencies in immortal rodent
      fibroblasts. Cellular p53 status will be an important factor to consider when
      performing functional analysis of the increasing number of mammalian proteins
      that are found to be involved in homologous recombination.

PMID- 10947119
TI  - Radiolysis of nucleosome core DNA: a modelling approach.
AB  - PURPOSE: To calculate the expected pattern of frank strand breaks (FSB) induced
      in the DNA of a nucleosome core particle (NCP) by the attack of radiolytic OH*
      radicals and to compare this with the experimental pattern of FSB induced by the
      in vitro irradiation of chicken NCP. MATERIALS AND METHODS: The structure of NCP
      was obtained from the PDB databank. Using molecular modelling, the structure of a
      linear DNA fragment with the central 60 bp sequence of NCP-DNA was determined.
      The accessibility of the sugar attack sites to OH* radicals at each nucleotide of
      the linear fragment or of the NCP-DNA was calculated. The probability of reaction
      of OH* with each sugar reactive site was calculated using a Monte-Carlo method
      based stochastic model. RESULTS: The accessibility of attack sites in the NCP-DNA
      and the calculated probabilities of sugar attack are mainly modulated through
      masking by histones, and only slightly through bending. The periodicity of the
      calculated FSB probabilities is identical to that of the experimental FSB
      probabilities in chicken NCP (period 10.4 +/- 0.1 bp). CONCLUSIONS: The good
      agreement between the calculated and experimental results recommends the
      presented modelling procedure as a tool in predicting the radiosensitivity of DNA
      in DNA-ligand complexes of known structure.

PMID- 10947120
TI  - Spin transfer from protein to DNA in X-irradiated 'dry' and hydrated chromatin:
      an electron spin resonance investigation of spectral components between 77 K and
      room temperature.
AB  - PURPOSE: To investigate the potential total and relative free-radical transfer
      from histones to DNA in X-irradiated chromatin, by analysing the relative
      contributions of individual radicals from protein and from DNA. MATERIALS AND
      METHODS: Chromatin was isolated from calf thymus, freeze-dried and either used as
      such or after equilibration at 76% relative humidity. A mixture of histones was
      purchased. X-irradiation was performed at 77 K (liquid nitrogen). Data
      acquisition was on a Bruker ESP 380 ESR-spectrometer (X-band, 9.5 GHz) and at
      high magnetic fields (285 GHz, Y-band, GHMFL Grenoble). Data analysis involved
      computer treatment of spectra. RESULTS: Three components were isolated from an
      annealing series of histones and assigned to specific radicals (X-band).
      Chromatin revealed the existence of radicals from both DNA, as well as from the
      histone compartment. The presence of the oxidized guanine base, as well as the
      reduced cytosine and thymine bases from DNA at 77 K was confirmed by high-field
      ESR. Relative radical yields were determined by superposition of individual
      components from DNA and histones in order to give complete reconstructions of the
      experimental spectra of the annealing series. CONCLUSIONS: The relative yields of
      individual radicals in chromatin differ from those in histones or DNA,
      respectively. Their behaviour upon annealing is, on the other hand, not
      significantly changed. Since the total radical yield of DNA radicals is about two
      times higher in the chromatin complex than in pure DNA, the hypothesis of spin
      transfer from protein to DNA prior to radical stabilization at 77 K is
      substantiated.

PMID- 10947121
TI  - The role of higher-order chromatin structure in the yield and distribution of DNA
      double-strand breaks in cells irradiated with X-rays or alpha-particles.
AB  - PURPOSE: To determine whether the non-random distributions of DNA double-strand
      breaks in cells observed after alpha-particle irradiation are related to the
      higher-order structure of the chromatin within the nucleus. MATERIALS AND
      METHODS: Chinese hamster V79 cells were irradiated as either cellular monolayers,
      nuclear monolayers with condensed chromatin or nuclear monolayers with relaxed
      chromatin, and the yields and distribution of DSB measured using two pulsed-field
      gel electrophoresis protocols capable of separating fragments of 10kbp to 5.7
      Mbp. RESULTS: Using conventional FAR analysis, the effect of isolating nuclear
      monolayers and changing the chromatin condensation state was less for alpha
      particle irradiated substrates than for X-irradiated ones. When the total number
      of breaks was measured by separating and quantifying all the fragments produced
      in the 10kbp to 5.7Mbp region, the difference between the observed yields of
      breaks in X-irradiated cells (7.3 x 10(-9) DSB/Gy/bp) relative to alpha-particles
      (12.1 x 10(-9) DSB/Gy/bp) was largely removed when nuclear monolayers with
      decondensed chromatin were exposed. The yields, although similar, increased to
      44.4 x 10(-9) DSB/Gy/bp for X-irradiated decondensed nuclear monolayers and 46.6
      x 10(-9) DSB/Gy/bp for alpha-particle irradiated monolayers. However, the alpha
      particle DSB distributions remained non-random. CONCLUSIONS: Our results suggest
      that the non-random distribution of breaks observed in cells with alpha-particle
      irradiation, which leads to a high probability for the production of regionally
      multiply damaged sites, is not related to the underlying chromatin condensation
      state present in the nucleus.

PMID- 10947122
TI  - DNA DSB induction and rejoining in V79 cells irradiated with light ions: a
      constant field gel electrophoresis study.
AB  - PURPOSE: To study the induction and the time-course of rejoining of DNA double
      strand breaks (DSB) in V79 cells irradiated with light ions with different linear
      energy transfer (LET). MATERIALS AND METHODS: V79 cells were irradiated in
      monolayer with monoenergetic proton, deuteron, helium-3 or helium-4 ion beams,
      each at two different energy values. Gamma rays were used as reference radiation.
      DSB have been measured by constant field gel electrophoresis (CFGE). RESULTS: The
      initial yield depended little on the particle type and LET. The amount of DSB
      left unrejoined for up to 2 h incubation time could be roughly described by a
      decreasing exponential function with a final plateau, although more complex
      functions cannot be excluded. Radiation quality had little effect on the
      rejoining rate but affected the plateau. The amount of residual DSB after 2 h was
      higher for densely than for sparsely ionizing radiation, and for the same
      particle was dependent on LET. The corresponding RBE ranged from 1.8 to 6.0.
      CONCLUSIONS: The results support the hypothesis that complex, less reparable DSB
      are induced in higher proportion by light ions with respect to gamma-rays and
      that, for the same ion, increasing LET leads to an increase in this proportion.

PMID- 10947123
TI  - Different cellular basis for the resistance of C3H and STS strain mice to the
      development of thymic lymphomas following fractionated whole-body irradiation:
      analysis using radiation bone marrow chimeras.
AB  - PURPOSE: B10 strain mice are susceptible to the induction of thymic lymphomas by
      fractionated whole-body X-irradiation (FI), whereas C3H and STS mice are
      resistant. The nature of the factors responsible for the strain difference in the
      susceptibility to thymic lymphomagenesis was investigated by using radiation bone
      marrow chimeras. METHODS: Radiation bone marrow chimeras were constructed in the
      reciprocal donor-host combinations of susceptible and resistant mice with use of
      Thy 1 markers that allow the genetic origins of thymocytes and thymic lymphomas
      to be determined. RESULTS: B10.Thy 1.1-->C3H, B10.Thy 1.1-->STS as well as
      B10.Thy 1.1-->B10 bone marrow chimeras manifested a high incidence of thymic
      lymphomas after FI-treatment, whereas C3H.Thy 1.1-->B10 and STS-->B10.Thy 1.1 as
      well as C3H.Thy 1.1-->C3H and STS-->STS chimeras manifested a low incidence of
      thymic lymphoma. Furthermore, FI-treatment of (B10.Thy 1.1+C3H)-->B10.Thy 1.1
      mixed chimeras resulted in the generation of similar numbers of thymic lymphomas
      of B10 and C3H origins, whereas FI-treatment of (B10.Thy 1.1+STS)--> B10.Thy 1.1
      mixed chimeras preferentially induced thymic lymphomas of B10 origin.
      CONCLUSIONS: (1) genetic factors responsible for the strain-dependent
      susceptibility and/or resistance to FI-induced lymphomagenesis exert their
      effects entirely on bone-marrow derived cells, (2) host environments of C3H and
      STS resistant mice are not inhibitory for the development of thymic lymphomas and
      (3) the resistance of STS mice to FI-induced thymic lymphomagenesis is an
      intrinsic property of thymocytes, whereas C3H and B10 thymocytes themselves are
      similarly susceptible for FI-induced thymic lymphomagenesis.

PMID- 10947124
TI  - Prevention of radiation-induced mammary tumours in rats by combined use of WR
      2721 and tamoxifen.
AB  - PURPOSE: This investigation evaluated the inhibitory effect of S-2-(3
      aminopropylamino)-ethylphosphorothioic acid (WR-2721) against the initiation of
      mammary tumourigenesis by irradiation, and the antipromotion activity of
      tamoxifen in the development of radiation-initiated mammary tumours. MATERIALS
      AND METHODS: Lactating rats were injected with WR-2721 and then irradiated with
      gamma-rays (1.5 Gy) at day 21 of lactation. The rats were divided into three
      groups 1 month after irradiation and were implanted with a pellet either of
      cholesterol as an inert control, diethylstilbestrol (DES) as a tumour-promoting
      agent, or DES combined with tamoxifen. For the control experiments, non
      irradiated and irradiated rats receiving saline instead of WR-2721 were treated
      with a pellet by the same procedures. RESULTS: The highest incidence (85%) for
      tumourigenesis of mammary glands was observed in the irradiated rats that had
      been previously injected with saline following treatment with DES Administration
      of WR-2721 prior to the irradiation significantly decreased the incidence of
      mammary tumours to 52.2%. The treatment with DES pellets combined with tamoxifen
      in the irradiated rats previously injected with saline also markedly suppressed
      the incidence of mammary tumours even further to 4.4%. Also, the development of
      mammary tumours was completely prevented in the rats treated with WR-2721 prior
      to irradiation and then implanted with DES pellets combined with tamoxifen.
      CONCLUSIONS: These results suggest that the administration of WR-2721 prior to
      irradiation has an inhibitory effect on the initiation phase, resulting in a
      partial reduction of mammary tumour development, and that the combination of WR
      2721 at the initiation phase with tamoxifen at the promotion phase is quite
      effective in preventing mammary tumourigenesis induced by radiation.

PMID- 10947126
TI  - Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha
      particles and gamma-irradiation: analysis of cell survival and microdosimetry.
AB  - PURPOSE: This study was designed to compare the cytotoxic effects of an alpha
      emitting radioimmunoconjugate, which binds to osteosarcoma but not to bone marrow
      cells, with those of external gamma-irradiation. MATERIALS AND METHODS: The human
      osteosarcoma cell line, OHS-s1, and mononuclear cells from bone marrow (BM)
      harvested from healthy donors, were used for these experiments. Cells in
      suspension were added to various activity concentrations of the anti-osteosarcoma
      monoclonal antibody TP-3 radiolabelled with 211At. Following incubation for 1 h,
      unbound radioactivity was washed off and cell survival was determined from
      clonogenic assays. Microdosimetry was calculated based on binding and retention
      kinetics of 211At to the cells, as well as cellular and nuclear diameters. For
      comparison, cell suspensions were irradiated with a single dose of 60Co gamma
      rays. RESULTS: 211At-labelled TP-3 showed heterogeneous binding to OHS-s1 cells,
      with a considerable variation among experiments. About 78% of the initially bound
      211At decayed while associated with the OHS-s1 cells. D0 values estimated by
      microdosimetry were 0.33 (0.22-0.48, range) Gy and 1.18 (0.89-1.89) Gy for OHS-s1
      and BM cells, respectively, whereas D0 values after external beam irradiation
      were 0.86+/-0.07Gy and 1.71+/-0.22Gy. The relative biological effectiveness (RBE)
      of 211At-labelled TP-3 at 37% survival was 3.43 for OHS-s1 and 1.55 for BM.
      CONCLUSIONS: High-LET targeted alpha-particle exposure killed osteosarcoma cells
      more effectively than bone marrow cells, although heterogeneous antigen
      expression among these tumour cells limited the magnitude of this effect.

PMID- 10947125
TI  - Induction by carbon-ion irradiation of the expression of vascular endothelial
      growth factor in lung carcinoma cells.
AB  - PURPOSE: To investigate the induction by carbon- ion irradiation of vascular
      endothelial growth factor (VEGF) mRNA and protein. MATERIALS AND METHODS: RERF-LC
      AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3,
      50 or 90keV/microm. Colony formation was used to determine cell survival. VEGF
      mRNA and protein of the irradiated cells were quantified by Northern blot
      analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor
      and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression.
      RESULTS: The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and
      90keV/microm) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values.
      Single doses of 15 Gy with either X-rays or carbon ions significantly induced
      VEGF mRNA expression at 16-24h after irradiation with a maximum induction of 2.81
      fold. A significant increase was also observed in VEGF protein levels, detected
      in culture supernatant 24h after irradiation with 50 and 90keV/microm carbon
      ions. Neither mRNA nor protein induction showed a dependence on LET. The
      induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by
      pretreating cells with genistein and H7, indicating that Src tyrosine kinase and
      protein kinase C on cell surface membranes is involved in the induction.
      CONCLUSION: Irradiation of lung carcinoma cells with carbon ions induced VEGF
      mRNA expression and increased protein levels. The induction was dose-dependent.
      Radiation-induced DNA damage and/or its repair may not be a prerequisite for the
      induction of VEGF mRNA.

PMID- 10947127
TI  - Effects of low dose radiation therapy on adjuvant induced arthritis in rats.
AB  - PURPOSE: Substantial clinical evidence shows the efficacy of low dose
      radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental
      investigations into these empirically clinical observations remain scarce. This
      study investigated in vivo the effects of daily 5 x 1.0 Gy versus 5 x 0.5 Gy on
      adjuvant induced arthritis in rats in order to explore whether there is a dose
      dependence of anti-inflammatory efficacy. MATERIALS AND METHODS: Adjuvant
      arthritis in female Lewis rats was induced by intradermal injection of heat
      inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated
      daily from days 15 to 19 after induction according to four protocols (15
      animals/group): group 1, 5 x 1.0 Gy (non-arthritic animals); group 2, sham
      irradiated control; group 3, 5 x 1.0 Gy; group 4, 5 x 0.5 Gy. The clinical
      parameters arthritis score (AS), hind paw volume (HPV), body weight, and
      erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30
      histological sections of at least 12 ankle joints per group were analysed semi
      quantitatively. RESULTS: Local irradiation of non-arthritic rats (group 1) with 5
      x 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group
      2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 x 1
      Gy (group 3) or 5 x 0.5 Gy (group 4) led to a reduction of mean AS from day 21 to
      29 compared with group 2 (days 27-29--group 3: p=0.037; group 4: p=0.034), with
      no differences in efficacy between groups 3 and 4. Concurrently, following
      radiation treatment there was no further increase in HPV. At the end of the
      observation period, this effect demonstrated a dose-dependent level of
      significance (days 27-29--group 3: p=0.0036; group 4: p=0.039). A significant
      decrease in the ESR was noted in both irradiated arthritic groups on day 21
      (group 3: p=0.015; group 4: p=0.006). The histopathological analysis revealed a
      highly significant reduction of cartilage and bone destruction on day 30 in both
      irradiated groups. CONCLUSIONS: This study confirms by objective criteria the
      anti-inflammatory efficacy of low dose RT and gives some indication for a dose
      dependence of its efficacy.

PMID- 10947128
TI  - Does coffee protect against the development of Parkinson disease (PD)?

PMID- 10947129
TI  - Does the addition of mouth-to-mouth ventilation to chest compressions improve
      survival in bystander treatment of cardiac arrest?

PMID- 10947131
TI  - Is electron-beam computed tomography (EBCT) a reliable tool for predicting
      coronary outcomes in an asymptomatic population?

PMID- 10947130
TI  - Does nefazadone alone, the cognitive behavioral-analysis system of psychotherapy,
      or the combination of both work best for patients with chronic depression?

PMID- 10947132
TI  - Do African American asthmatics perceive and describe their asthma symptoms
      differently than white asthmatics?

PMID- 10947133
TI  - Childhood cancer survivors and primary care physicians.

PMID- 10947134
TI  - The natural history of cervical cryosurgical healing. The minimal effect of
      debridement of the cervical eschar [see comment].
AB  - BACKGROUND: Cryosurgery is a favored treatment method for cervical
      intraepithelial neoplasia (CIN) among family physicians, in part because it is
      inexpensive and requires the least technical training and skill. Although
      cervical cryosurgery has been used for more than 30 years, the natural history of
      the postprocedure process has never been described. The primary purpose of our
      study was to describe the natural history of the healing process after cervical
      cryosurgery. A secondary purpose was to determine the effect of mechanical
      debridement of the cervical eschar on the symptoms of healing. METHODS: We
      conducted a prospective multicentered trial in which women who had a histologic
      ally documented CIN lesion underwent cervical cryosurgery. Forty-six women were
      randomized to undergo eschar debridement at 48 hours after cryosurgey, and 38
      women received standard care. All women were followed up and given preweighed
      sanitary pads for hydrorrhea (watery discharge) collection and a diary to record
      the severity and number of days of odor, pain, cramping, and hydrorrhea that were
      experienced. RESULTS: The average total amount of hydrorrhea or discharge was 288
      g, which required using an average of 41 sanitary pads during a period of 12.4
      days. The duration of odor was 8.9 days, and the pain and cramping experienced
      after cryosurgery lasted 4.7 days. Women who were obese had greater hydrorrhea
      and pad usage than nonobese women. Debridement of the cervical eschar did not
      significantly change the signs and symptoms of healing after cryosurgery.
      CONCLUSIONS: There are significant symptoms patients experience after cryosurgery
      that are not ameliorated by debridement. The expectations of the cryosurgical
      healing process should be disclosed to women before the procedure.

PMID- 10947135
TI  - Healing experiences after cervical cryosurgery.
AB  - BACKGROUND: Treatment for cervical intraepithelial neoplasia with cryosurgery is
      uncomfortable for many women. The subsequent healing process is also thought to
      bring discomfort. The purpose of our study was to describe women's experiences
      after cryosurgery, and how obesity, age, and gravidity affected, the healing
      process. METHODS: We developed a survey from focus group results to measure the
      unpleasantness of hydrorrhea (watery discharge) from cryosurgery, the pad
      protection required, and the odor associated with the hydrorrhea. The
      cryosurgical experiences were compared with normal menses for the use and
      frequency of pad protection, medications used, and any activity restrictions.
      RESULTS: Cryosurgical experiences were unpleasant for 78.3% of the women because
      of the pain and cramping of the procedure and the resulting hydrorrhea, odor, and
      necessity of wearing pads for protection. These experiences after cryosurgery
      caused 38.6% to restrict their activities and 67.1% to take medications, a
      significantly greater proportion than the 16.9% whose activities were restricted
      normal menses and the 26.8% who took medications for normal menses (P=-.004, P
      <.001, respectively). In addition to these experiences, obese, multigravid, and
      older women were more bothered by the duration of wearing pads than their
      counterparts (P=.0246, =.0061, and P=.0159, respectively). CONCLUSIONS: Our study
      showed that the cryosurgical healing process was not pleasant, and was least
      tolerable for obese, multigravid, and older women. As many as 50% of women
      undergoing cryosurgery will perceive the hydrorrhea, its odor, and the wearing of
      pads to be worse than normal menses, especially if their menses are usually
      light.

PMID- 10947136
TI  - Cryotherapy: evidence-based interventions and informed consent.

PMID- 10947137
TI  - Management of laboratory test results in family practice. An OKPRN study.
      Oklahoma Physicians Resource/Research Network.
AB  - BACKGROUND: Ineffective management of laboratory test results can result in
      suboptimal care and malpractice liability. However, there is little information
      available on how to do this important task properly in primary care settings.
      METHODS: We used a questionnaire guided by a literature review to identify a
      conceptual model, current practices, and clinicians who reported having an
      effective method for at least one of 4 steps in the process of managing
      laboratory test results. Clinicians with differing methods were selected for each
      of the steps. Practice audits and patient surveys were used to determine actual
      performance. On the basis of these audits, we constructed a unified best method
      and conducted time-motion studies to determine its cost. RESULTS: After auditing
      only 4 practices we were able to identify effective methods for 3 of the 4 steps
      involved in the management of laboratory test results. The unified best method
      costs approximately $5.19 per set of tests for an individual patient.
      CONCLUSIONS: By identifying effective practices within a family practice research
      network, an effective method was identified for 3 of the 4 steps involved in the
      management of laboratory test results in primary care settings.

PMID- 10947139
TI  - Targeting quality improvement activities for depression. Implications of using
      administrative data.
AB  - BACKGROUND: Large health care organizations may use administrative data to target
      primary care patients with depression for quality improvement (QI) activities.
      However, little is known about the patients who would be identified by these data
      or the types of QI activities they might need. We describe the clinical
      characteristics and outcomes of patients identified through administrative data
      in 2 family practice clinics. METHODS: Patients with depression aged 18 to 65
      years were identified through review of encounter/administrative data during a 16
      month period. Patients agreeing to participate (N=103) were interviewed with the
      Primary Care Evaluation of Mental Disorders questionnaire and completed the
      Depression Outcomes Modules (with an embedded Medical Outcomes Short Form-36 [SF
      36]), Symptom Check List-25 (SCL-25), and Alcohol use Disorders Identification
      Test. Follow-up assessments were completed by 83 patients at a median of 7
      months. RESULTS: A large majority of identified patients (85%) met full criteria
      for a Diagnostic and Statistical Manual of Mental Disorders depressive disorder;
      those not meeting criteria usually had high levels of symptoms on the SCL-25.
      Seventy-seven percent of the patients reported recurrent episodes of depressed
      mood, and 60% reported chronic depression. Although most improved at follow-up,
      they continued to have substantial functional deficits on the SF-36, and 60%
      still had high levels of depressive symptoms. CONCLUSIONS: QI programs that use
      administrative data to identify primary care patients with depression will select
      a cohort with relatively severe, recurrent depressive disorders. Most of these
      patients will receive standard treatments without QI interventions and will
      continue to be symptomatic. QI programs targeting this population may need to
      offer intensive alternatives rather than monitor standard care.

PMID- 10947138
TI  - Managing patient information longitudinally. It's about time.

PMID- 10947140
TI  - Reconnoitering the antivaccination web sites: news from the front.
AB  - BACKGROUND: In the United States, Western Europe and other areas, groups opposing
      universal childhood immunization are reported to be gaining political momentum.
      METHODS: A review was done of Internet sites opposing childhood immunization,
      with the goal of describing the philosophies and strategies used by the groups
      presenting them. A random sample of antivaccination Web sites was obtained using
      standard Internet search engines and the search terms "vaccination" and
      "immunization." These sites were analyzed for content, common themes, philosophy,
      affiliation with groups or organizations, and suggested strategies for avoiding
      vaccination. RESULTS: Twenty-six of the 51 sites found were randomly selected for
      review. Fifteen of these were associated with groups promoting the use of
      alternative medicine for preventing or treating infectious disease. Groups
      concerned with civil liberties were also represented, as were conspiracy
      theorists. CONCLUSIONS: Many groups have an interest in opposing universal
      childhood immunization, and some of them have a prominent presence on the
      Internet. Physicians and parents should be aware of the existence of these groups
      and their philosophies. Further research and educational efforts to counter their
      effects is necessary.

PMID- 10947141
TI  - Body mass index and quality of life in a survey of primary care patients.
AB  - BACKGROUND: The prevalence of overweight and obesity is increasing and
      contributes to the burden of ill health in the community. The impact of obesity
      on health-related quality of life has been less well studied than how it affects
      physical morbidity and mortality. METHODS: A survey of health-related quality of
      life using the 12-item Short Form (SF-12) of the Medical Outcomes Study Short
      Form-36 was mailed to patients attending a family medicine clinic. Multiple
      regression analyses were used to investigate the relationships between scores on
      the mental and physical components of the SF-12 and body mass index (BMI) while
      controlling for age, sex, and family income. RESULTS: Responses were received
      from 565 subjects (53%). The relationships among BMI and quality of life in the
      mental and physical domains were nonlinear. Quality of life scores were optimal
      when BMI was in the range of 20 to 25 kg per m2. CONCLUSIONS: The National Heart,
      Lung, and Blood Institute has published evidence-based clinical guidelines for
      the identification, evaluation, and treatment of overweight and obesity in
      adults. Subjects with BMI in the range 18.5 to 24.9 kg per m2 are classified as
      having normal weight. These observations suggest that achieving a weight in this
      range will maximize the patient's subjective sense of well-being.

PMID- 10947142
TI  - Liquid medication dosing errors.
AB  - BACKGROUND: Our goal was to examine the following issues relevant to the use of
      liquid medications: (1) which liquid medication dosing devices are commonly owned
      and used; (2) the ability of potential patients to accurately measure liquids
      using 3 different dosing devices; (3) their ability to correctly interpret a
      variety of dosing instructions; and (4) their ability to correctly interpret a
      pediatric dosing chart. METHODS: One hundred thirty volunteers from the waiting
      areas of 3 primary care clinics in the St. Paul, Minnesota, area were
      interviewed. Participants were shown 7 liquid dosing devices and were asked which
      they had in their homes and which they had ever used. The participants were
      tested and scored on their ability to measure liquid medicines and interpret
      dosing instructions accurately. The total performance score was determined, with
      a maximum obtainable score of 11. RESULTS: A household teaspoon was the device
      most frequently used for measuring liquid medication. Women and participants with
      more education had higher total performance scores. Common errors included
      misinterpreting instructions, confusing teaspoons and tablespoons on a medicine
      cup, and misreading a dosage chart when weight and age were discordant.
      CONCLUSIONS: Clinicians need to be aware that many people continue to use
      inaccurate devices for measuring liquid medication, such as household spoons.
      They should encourage the use of more accurate devices, particularly the oral
      dosing syringe. Clinicians should always consider the possibility of a medication
      dosing error when faced with an apparent treatment failure.

PMID- 10947143
TI  - A systematic review of troponin T and I values as a prognostic tool for patients
      with chest pain.
AB  - OBJECTIVE: The accuracy of the troponin T and I test as a prognostic tool for
      patients with chest pain varies considerably depending on the patient population,
      the cutoff for an abnormal test result, and other factors. The goal of our
      systematic review was to synthesize the best available evidence on this topic.
      SEARCH STRATEGY: We searched the MEDLINE database, bibliographies of identified
      articles, and articles identified from a previous meta-analysis of diagnosis.
      SELECTION CRITERIA: We included cohort studies that had at least 80% follow-up
      and reported useful data. DATA COLLECTION AND ANALYSIS: Data from each study were
      abstracted by 2 investigators. We calculated sensitivity and specificity for the
      prediction of death, fatal or nonfatal myocardial infarction (MI), or any cardiac
      event for each combination of patient population, troponin test, interval from
      admission to blood draw, and cutoff for an abnormal test result. MAIN RESULTS:
      For patients with chest pain and a normal electrocardiogram, the peak troponin I
      level drawn 6 or more hours after the onset of chest pain is useful for
      identifying patients at low risk of death or nonfatal MI at 30 days (negative
      likelihood ratio=0.07; probability of outcome=0.3% with a negative test, given a
      pretest probability of 4.4%). For patients with unstable angina, the sensitivity
      of troponin I for the identification of patients who die or have a nonfatal MI in
      the next 30 days is only 59%, and the specificity is only 79%. The sensitivity
      and specificity varied widely for patients with unstable angina or non-Q-wave MI
      depending on the inclusion criteria, cutoff used, timing of the blood draw,
      duration of follow-up, aim other factors. CONCLUSIONS: If the peak troponin T or
      I level measured at least 6 hours after the onset of chest pain symptoms is in
      the normal range in a patient with a normal electrocardiogram, it is very
      unlikely that the patient will die or have a nonfatal MI in the next 30 days (<
      or =1%). The initial troponin value is not as helpful as the peak value at least
      6 hours after the onset of chest pain. An abnormal troponin test result for
      patients with unstable angina or non-Q-wave MI identifies a subset at greater
      risk of death.

PMID- 10947144
TI  - Is losartan superior to captopril in reducing all-cause mortality in elderly
      patients with symptomatic heart failure?

PMID- 10947145
TI  - Is there a clinical difference in outcomes when beta-agonist therapy is delivered
      through metered-dose inhaler (MDI) with a spacing device compared with standard
      nebulizer treatments in acutely wheezing children?

PMID- 10947146
TI  - Is there a simple and accurate algorithm that clinicians can use to more
      effectively select women for bone densitometry testing?

PMID- 10947147
TI  - Effect of gender and sex hormones on immune responses following shock.
AB  - Several clinical and experimental studies show a gender dimorphism of the immune
      and organ responsiveness in the susceptibility to and morbidity from shock,
      trauma, and sepsis. In this respect, cell-mediated immune responses are depressed
      in males after trauma-hemorrhage, whereas they are unchanged or enhanced in
      females. Sex hormones contribute to this gender-specific immune response after
      adverse circulatory conditions. Specifically, studies indicate that androgens are
      responsible for the immunodepression after trauma-hemorrhage in males. In
      contrast, female sex steroids seem to exhibit immunoprotective properties after
      trauma and severe blood loss, because administration of estrogen prevents the
      androgen-induced immunodepression in castrated male mice. Nonetheless, the
      precise underlying mechanisms for these immunomodulatory effects of sex steroids
      after shock remain unknown. Although testosterone depletion, testosterone
      receptor antagonism, or estrogen treatment has been shown to prevent the
      depression of immune functions after trauma-hemorrhage, it remains to be
      established whether differences in the testosterone-estradiol ratio are
      responsible for the immune dysfunction. Furthermore, sex hormone receptors have
      been identified on various immune cells, suggesting direct effects. Thus, the
      immunomodulatory properties of sex hormones after trauma-hemorrhage might
      represent novel therapeutic strategies for the treatment of immunodepression in
      trauma patients.

PMID- 10947148
TI  - Production of IL-6 and MCP-1 by the human peritoneum in vivo during major
      abdominal surgery.
AB  - Both inflammatory and anti-inflammatory mediators are released into the
      circulation during major abdominal surgery. In addition, some of these mediators
      have been detected postoperatively in peritoneal fluids. Thus, it appears that
      the peritoneum may be a potential source of circulating immunomodulators
      following major abdominal surgery. With this in mind, we quantified the
      intraoperative production of interleukin (IL)-6 and monocyte chemoattractant
      protein-1 (MCP-1) by human peritoneum. A small chamber was sewed to the parietal
      peritoneum of 19 patients at the beginning of the operation. This chamber was
      perfused with buffered salt solution, and the perfusate was collected hourly and
      assayed for IL-6 and MCP-1 concentrations by enzyme-linked immunosorbent assay.
      Expression of the corresponding mRNAs was determined by reverse-transcription
      polymerase chain reaction from additional peritoneal biopsies taken at the
      beginning and at the end of operation. Peritoneal production of IL-6 and MCP-1
      started within the first hour of operation and continued with increasing amounts
      of up to 435 (43-1925) pg/cm2/h [median (range)] of IL-6 and 435 (59-1930)
      pg/cm2/h of MCP-1. There was induction of peritoneal IL-6 and MCP-1 mRNA
      expression. A suppressed MCP-1 production was seen only in one patient who
      suffered from severe septic complications in the postoperative course. Using a
      new technique that allows for the quantification of local cytokine production in
      vivo, we demonstrated that the peritoneum rapidly reacts to abdominal surgery
      with increased production of IL-6 and MCP-1. Early detection of impaired
      production may help to identify patients at risk of postoperative septic
      complications.

PMID- 10947149
TI  - Interleukin-8 as a predictor of the severity of bacteremia and infectious
      disease.
AB  - The relationship between cytokines and sepsis has been studied frequently in the
      intensive care unit (ICU). However, the determination of cytokines in patients as
      they enter the emergency department (ED) would be more meaningful in predicting
      the outcome of infection. This study investigated plasma interleukin-8 in the ED
      as the predictor of bacteremia and sepsis. One hundred patients admitted through
      the ED with signs of systemic inflammatory response syndrome were studied. Plasma
      IL-8, IL-6, and tumor necrosis factor (TNF) were assayed by enzyme-linked
      immunosorbent assay. Patient's data were evaluated using the APACHE II scoring
      system as predictive factors of morbidity and mortality. Plasma IL-8 (149 pg/mL)
      detected bacteremia with a positive predictive value of 90.9% and a specificity
      of 98.7%. Results indicated that the odds ratios (ORs) of bacteremia were 24.78
      (P < 0.01, CI = 2.27-270.8), 5.42 (P < 0.05, CI = 1.37-21.4), and 6.05 (P < 0.05,
      CI = 1.36-26.8) for IL-8, IL-6, and APACHE II, respectively. Occurrence of
      bacteremia was highly correlated with increases in plasma IL-8 (P < 0.01). IL-8
      (OR = 8.25, CI = 1.03-65.9) and APACHE II scores (OR = 12.6, CI = 2.24-70.4) were
      found to be significantly better predictive factors of mortality (P < 0.01) than
      IL-6 (OR = 3.60, CI = 0.57-22.7), TNF (OR = 0.24, CI = 0.01-11.0) and age (OR =
      1.02, CI = 0.98-1.06). During bacteremia, IL-8 also correlated well with patient
      use of a ventilator (P < 0.01, OR = 2.43, CI = 2.41-311.19), use of vasopressors
      (P < 0.05, OR = 2.67, CI = 1.79-370.78), length of stay in the hospital (P <
      0.01, OR = 3.14, CI = 1.87-988.31), and stay in the ICU (P < 0.01, OR = 2.51, CI
      = 2.98-449.80). Measuring IL-8 on patients in the ED with apparent bacterial
      infections appears to be a reliable predictor of bacteremia and the severity of
      disease.

PMID- 10947150
TI  - Prospectively validated prediction of organ failure and hypotension in patients
      with septic shock: the Systemic Mediator Associated Response Test (SMART).
AB  - Conventional outcomes research provides only percentage risk categories that are
      not applicable to individual patients, and it predicts only mortality,
      utilization of resources and/or broad groupings of multiple organ system
      dysfunction. The purpose of the present study was to determine whether or not the
      Systemic Mediator Associated Response Test (SMART) methodology could identify
      interactions among demographics, physiologic parameters, standard hospital
      laboratory tests, and circulating cytokine concentrations to predict continuous
      and dichotomous dependent clinical variables, in advance, in individual patients
      with septic shock and to integrate these into prospectively validated models. Two
      hundred forty (240) patients with septic shock who were entered into the placebo
      arm of a multi-institutional clinical trial were randomly separated into a model
      building training cohort (n = 154) and a predictive cohort (n = 86), which was
      used to prospectively validate the prognostic models built upon the training
      cohort database. From baseline patient demographics; hospital laboratory tests;
      and plasma levels of interleukin-6, interleukin-8, and granulocyte colony
      stimulating factor, multiple regression models were developed that predicted
      clinically important continuous dependent variables quantitatively in individual
      patients. Multivariate stepwise logistic regression was utilized to develop
      models that prognosticated dichotomous dependent end points. At the completion of
      the modeling process, baseline data from individual patients in the predictive
      cohort was inserted into each multivariate model for each day. Prospective
      validation was accomplished by simple linear regression of individual predicted
      versus observed values for continuous dependent variables, and by establishing
      the Receiver Operator Characteristics Area Under the Curve (ROC AUC) for logistic
      regression models that predicted dichotomous end points. Through seven days,
      SMART quantitative predictions of selected physiologic and metabolic parameters
      were validated at r > 0.500 in 51%. Up to seven days after baseline, 31/49 (63%)
      SMART models for renal and liver function indicators were validated prospectively
      at the r > 0.700 level. For hematologic/coagulation models, 37/56 (66%) up to
      seven days had r > 0.900. Among dichotomous models, ROC AUC > 0.700 was achieved
      in 30/49 (61%) during the first week. SMART integration of demographics, bedside
      physiology, hospital laboratory tests, and circulating cytokines predicts organ
      failure and physiologic function indicators in individual patients with septic
      shock.

PMID- 10947151
TI  - Soluble fas levels correlate with multiple organ dysfunction severity, survival
      and nitrate levels, but not with cellular apoptotic markers in critically ill
      patients.
AB  - Apoptosis is a mode of programmed cell death (PCD). Transduction of apoptotic
      signals results in cellular suicide. Organ specific apoptosis has been proposed
      as a factor in multiple organ dysfunction syndrome (MODS). Fas is a widely
      occurring apoptotic signal receptor molecule expressed by almost any type of
      cell, which is also released in a soluble circulating form (circulating fas,
      sfas). In this exploratory study, we investigated the association of sfas with
      severity, survival, known mediators of multiple organ dysfunction, and cellular
      apoptotic markers on peripheral blood mononuclear cells (PBMC) in a group of 35
      patients with MODS and in 35 matched controls. Critically ill patients with MODS
      had significantly elevated sfas levels compared to controls over time (P < .001).
      Increased serum concentration of circulating fas was associated with increased
      severity of multiple organ dysfunction. Non-survivors exhibited significantly
      higher sfas levels compared to survivors (P < .01) and increasing sfas was
      inversely associated with the likelihood of survival (P < .05). Circulating fas
      levels correlated highly with serum nitrate concentration, but not with fas and
      fasL expression on PBMC of critically ill patients. TNF-alpha and IL-6, although
      they appear to be mediators of both apoptosis and MODS, had no association with
      sfas. These results are suggestive of the need for further investigation on the
      role of apoptotic signaling in the development of MODS. They also suggest a
      potential prognostic value of sfas for SIRS/MODS clinical outcomes.

PMID- 10947152
TI  - Role of neutrophils in burn-induced microvascular injury in the intestine.
AB  - The present study evaluated burn-induced vascular permeability alterations of rat
      small intestine in vivo and assessed the effect of neutrophil depletion in burn
      injured rats on the altered intestinal microvascular permeability. 125I-labeled
      bovine serum albumin (125I-BSA) was injected intravenously, and its leakage from
      circulation into the intestinal tissue was determined by measuring tissue counts
      of 125I-BSA. Compared with sham, vascular albumin permeability increased 1.7-fold
      on day 1 post-burn and 3.0-fold on day 3 post-burn in ileum. In the jejunum,
      albumin permeability increased 1.8- and 2.5-fold on day 1 and day 3 post-burn,
      respectively. Intestinal tissue edema, determined as increases in tissue water
      contents, was noted in both intestinal segments on day 1 post-burn; no further
      increase in edema was found on day 3 post-burn. Neutrophil depletion before burn
      injury prevented the vascular leakage of albumin and edema in the ileum and
      jejunum on day 1 post-burn. On day 3 post-burn, the effect of prior neutrophil
      depletion on vascular permeability was less marked, and edema formation was not
      affected at all. These findings indicate that an absence of neutrophils prevents
      the loss of intestinal vascular barrier properties only in the initial periods
      after burns.

PMID- 10947154
TI  - Prevention of systemic hyperlactatemia during splanchnic ischemia.
AB  - Arterial blood lactate increases as a result of poor tissue perfusion. In
      splanchnic hypoperfusion, increased hepatic lactate uptake may delay increases in
      arterial blood lactate. We hypothesized that during isolated reduction of
      mesenteric blood flow, maintaining systemic blood volume and flow by fluid
      resuscitation may prevent systemic hyperlactatemia and therefore mask splanchnic
      ischemia. In a randomized study, 7 pigs were subjected to 4 h of splanchnic
      hypoperfusion by reducing the superior mesenteric artery blood flow to 4 +/- 0.8
      mL/kg min [mean +/- standard deviation (SD)]. Seven pigs served as controls.
      Fluid was administered in order to keep the pulmonary artery occlusion pressure
      at 5 to 8 mm Hg. Cardiac output, portal vein, superior mesenteric, and hepatic
      arterial blood flow were measured every 30 min. Arterial, mixed venous, hepatic,
      portal, and mesenteric venous blood lactate, and jejunal mucosal pCO2 were
      measured at baseline and thereafter at 30-min intervals. The initial decrease in
      portal venous blood flow in the ischemic animals was subsequently counterbalanced
      by increasing hepatic arterial blood flow from 2 +/- 1 mL x kg(-1) x min(-1) at
      baseline to 11 +/- 4 mL x kg(-1) x min(-1) [after 4 h of ischemia; mean +/-
      standard deviation (SD), P = 0.02]. Jejunal mucosal- and mesenteric vein-arterial
      pCO2 gradients increased in the ischemic group from 11 +/- 8 mm Hg to 73 +/- 5 mm
      Hg (P = 0.02), and from 10 +/- 4 mm Hg to 44 +/- 8 mm Hg, respectively (P =
      0.02). Mesenteric and portal venous lactate increased in the ischemic animals
      from 1.1 +/- 0.3 mmol/L to 4.2 +/- 1.0 mmol/L (P = 0.02), and from 1.0 +/- 0.2
      mmol/L to 1.6 +/- 0.3 mmol/L, respectively (P = 0,03). While mesenteric lactate
      production and hepatic lactate uptake increased in parallel in the ischemic
      animals from 5 +/- 6 micromol x kg(-1) x min(-1) to 14 +/- 5 micromol x kg(-1) x
      min(-1) (P = 0.04), and from 14 +/- 7 micromol x kg(-1) x min(-1) to 24 +/- 6
      micromol x kg(-1) x min(-1), respectively (P = 0.02), hepatic venous and arterial
      lactate, and apparent splanchnic lactate uptake and extraction did not change. We
      conclude that the hepatic lactate uptake increases in response to hepatic lactate
      influx. Systemic hyperlactatemia and increased hepatic venous lactate
      concentrations are late consequences of mesenteric hypoperfusion if hypovolemia
      is prevented. The net exchange of lactate across the splanchnic region does not
      reflect hepato-portal lactate kinetics in this animal model of intestinal
      hypoperfusion.

PMID- 10947153
TI  - Activation of NF-kappaB varies in different regions of the gastrointestinal tract
      during endotoxemia.
AB  - The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of
      genes involved in the inflammatory response to sepsis and endotoxemia. We
      recently found that NF-kappaB is activated in the jejunal mucosa during
      endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal
      tract is not known. We hypothesized that NF-kappaB is differentially activated in
      different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA
      binding activity was determined by electrophoretic mobility shift assay in mucosa
      of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected
      mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and
      IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF
      kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding
      to smaller doses of endotoxin than the other parts of the gastrointestinal tract.
      NF-kappaB DNA binding activity was not induced in colonic mucosa, even following
      administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels
      decreased in jejunal mucosa of endotoxin injected mice, concomitant with
      activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB
      is activated in mucosa of stomach and small intestine, but not in colon, and that
      the jejunum is particularly sensitive to endotoxin.

PMID- 10947155
TI  - Suppression of Cox-2 and TNF-alpha mRNA in endotoxin tolerance: effect of
      cycloheximide, antinomycin D, and okadaic acid.
AB  - Lipopolysaccharide (LPS)-tolerant human promonocytic THP-1 cells produce
      decreased levels of inflammatory mediators such as eicosanoids and tumor necrosis
      factor alpha (TNFalpha) in response to LPS. We hypothesized that transcriptional
      repression by newly synthesized proteins may be a mechanism for the reduced
      cellular response to a secondary challenge with LPS. THP-1 cells were
      desensitized after a 3.5 h or 20 h pre-exposure to LPS (1 microg/mL) and
      subsequently challenged with LPS (10 microg/mL). In cells rendered tolerant by
      exposure to LPS for 20 h, LPS-induced expression of cyclooxygenase (Cox)-2 and
      TNFalpha mRNA was suppressed. Cycloheximide (10 microM) prevented the
      transcriptional down-regulation of Cox-2 mRNA and to a lesser extent, TNFalpha
      mRNA, in LPS-tolerant cells. Transcriptional arrest with actinomycin D stabilized
      steady-state expression of Cox-2 mRNA in naive and tolerant cells but
      destabilized TNFalpha mRNA expression in LPS-tolerant cells. The observation that
      in naive cells Cox-2 and TNFalpha mRNA levels subside at 3 to 4 h after LPS (10
      microg/mL or 1 microg/mL) suggested that LPS tolerance may occur earlier.
      Therefore, in subsequent experiments, the effect of LPS pretreatment for only 3.5
      h was examined. This abbreviated tolerance regimen diminished secondary LPS
      induced Cox-2 mRNA expression but had a lesser effect on TNFalpha mRNA
      expression. However, cycloheximide augmented both Cox-2 and TNFalpha mRNA
      expression in this group. Also, the serine/threonine phosphatase inhibitor
      okadaic acid augmented Cox-2 and TNFalpha mRNA expression in the LPS-tolerant
      cells. Although LPS-induced TNFalpha production in LPS-tolerant cells was
      suppressed relative to the naive cells, okadaic acid induced comparable levels of
      TNFalpha in tolerant and naive cells. These findings support the concept that LPS
      tolerance is associated with induction of proteins that alter expression of
      certain genes. Expression of Cox-2 mRNA appears to be particularly sensitive to
      down-regulation and, to a lesser extent, TNFalpha mRNA. However, this seems to
      vary depending on the LPS pretreatment regimen. The ability of a phosphatase
      inhibitor to induce TNFalpha and expression of Cox-2 and TNFalpha mRNA in LPS
      tolerance suggests that there may be alterations in phosphorylation status of
      signaling pathways, transcriptional mechanisms, or post-transcriptional mRNA
      stability.

PMID- 10947157
TI  - Inhibition of the activity of poly (ADP-ribose) polymerase in ischemia
      reperfusion injury.

PMID- 10947156
TI  - Poly (ADP-ribose) synthetase mediates intestinal mucosal barrier dysfunction
      after mesenteric ischemia.
AB  - Peroxynitrite-mediated DNA strand breaks trigger poly (ADP-ribose) synthetase
      (PARS) activation, resulting in intracellular energetic failure and organ
      dysfunction. We investigated the role of PARS activation on the inflammatory and
      functional response of the intestine to mesenteric ischemia-reperfusion injury.
      Anesthetized rats exposed to 15 min occlusion of the superior mesenteric artery
      showed an increased mucosal PARS activity (ex vivo incorporation of radiolabelled
      NAD+ in gut mucosal scrapings) as soon as 10 min after reperfusion. During the
      first 30 min of reperfusion, significant mucosal damage developed, as well as
      mucosal hyperpermeability to a 4000 MW fluorescent dextran (FD4). These
      alterations were significantly reduced by treatment with the NO synthase
      inhibitor L-NMA, which blocks the production of peroxynitrite, as well as with
      the PARS inhibitors 3-aminobenzamide and nicotinamide, whereas they were markedly
      enhanced by the glutathione depletor L-buthionine-(S,R)-sulfoximine. Also, PARS
      inhibition significantly reduced ileal neutrophil infiltration (myeloperoxidase
      activity) at 3 h reperfusion. In a second set of experiments, the effects of 15
      or 30 min ischemia followed by 3 h reperfusion were evaluated in PARS knockout
      and wild-type mice. Significant protection against histological damage,
      neutrophil infiltration, and mucosal barrier failure (evaluated by the mucosal-to
      serosal FD4 clearance of everted ileal sacs incubated ex vivo) was noted in PARS
      knockout mice, who also showed reduced alterations in remote organs, as shown by
      lesser lipid peroxidation (malondialdehyde formation) and neutrophil infiltration
      in the lung and liver. In conclusion, PARS plays a crucial role in mediating
      intestinal injury and dysfunction in the early and late phases of mesenteric
      reperfusion. Pharmacological inhibition of PARS may be a novel approach to
      protect tissues from reperfusion-related damage.

PMID- 10947158
TI  - Spermine differentially regulates the production of interleukin-12 p40 and
      interleukin-10 and suppresses the release of the T helper 1 cytokine interferon
      gamma.
AB  - Polyamines are endogenous immunomodulatory molecules. Recent studies revealed
      that polyamines suppress the production of proinflammatory cytokines and nitric
      oxide. In the present study, we investigated the effect of the polyamines
      spermine, spermidine, and putrescine on the production of interleukin (IL)-12
      p40, IL-10, and interferon (IFN-gamma) in mouse peritoneal macrophages and spleen
      cell suspensions. Spermine, but not spermidine or putrescine, suppressed, in a
      concentration-dependent manner, the production of IL-12 p40 by lipopolysaccharide
      (LPS)-stimulated macrophages. The effect of spermine was post-transcriptional,
      because steady-state levels of messenger ribonucleic acid (mRNAs) for IL-12 (p35
      and p40) were not affected. In contrast to its inhibitory effect on IL-12 p40,
      spermine (0.3-3 microM) augmented IL-10 production. The down-regulation of IL-12
      p40 by spermine was independent of enhancement of IL-10 by this agent, for
      spermine retained its ability to suppress IL-12 production in peritoneal
      macrophages obtained from IL-10-deficient mice. The alterations in cytokine
      production by spermine did not involve an effect on early intracellular pathways
      of LPS signal transduction, including the p38 or p42/44 mitogen-activated protein
      kinases, or the c-jun terminal kinase. In spleen cell suspensions, spermine
      suppressed the release of IFN-gamma induced either by LPS or anti-CD3 antibody.
      In summary, spermine exerts anti-inflammatory effects by suppressing IL-12 and
      IFN-gamma and by augmenting the production of IL-10.

PMID- 10947159
TI  - Beneficial effects of tempol, a membrane-permeable radical scavenger, in a rodent
      model of splanchnic artery occlusion and reperfusion.
AB  - The aim of the present study was to investigate the effects of tempol, a membrane
      permeable radical scavenger, in rats subjected to splanchnic artery occlusion
      shock (SAO). Rats subjected to SAO developed a significant decrease in mean
      arterial blood pressure, a significant increase in tissue myeloperoxidase
      activity, and a marked injury to the distal ileum. SAO shock resulted in 100%
      mortality at 2 h after reperfusion. At 60 min after reperfusion, a marked
      increase in the immunoreactivity to nitrotyrosine and to poly (ADP-ribose)
      synthetase was observed in the necrotic ileum of rats with SAO. Staining of
      sections of the ileum obtained from SAO-shocked rats with anti-intercellular
      adhesion molecule (ICAM-1) and anti-P-selectin antibodies resulted in diffuse
      staining. Tempol (30 mg/kg bolus injection 5 min prior to reperfusion, followed
      by an infusion of 30 mg/kg/h intravenously) attenuated 1) the infiltration of the
      reperfused intestine with neutrophils, 2) the lipid peroxidation, 3) the
      production of peroxynitrite, 4) the degree of P-selectin and ICAM-1 staining in
      tissue sections from SAO-shocked rats, 5) histological signs of bowel injury, and
      6) mortality at 2 h after reperfusion. Taken together, our results clearly
      demonstrate that the intracellular radical scavenger tempol reduces the
      intestinal injury of rats subjected SAO shock.

PMID- 10947160
TI  - Laparotomy prevents lethal endotoxemia in a murine sequential insult model by an
      IL-10-dependent mechanism.
AB  - Multiple organ dysfunction and death are common sequelae after mesenteric
      ischemia-reperfusion injury as seen with mesenteric revascularization and
      thoracoabdominal aortic aneurysm repair. A second insult such as bacterial
      pneumonia occurring subsequent to the ischemia-reperfusion injury may contribute
      to these untoward effects. We hypothesized the sequential visceral/lower torso
      ischemia-reperfusion and endotoxemia in a murine model would increase the
      magnitude of the proinflammatory cytokine response and decrease survival. C57BL/6
      mice underwent 20 min of supraceliac occlusion (IR), sham laparotomy (LAP), or no
      initial insult (CTRL) followed by intraperitoneal injection of a lethal dose of
      endotoxin (LPS [lipopolysaccharide 50 mg/kg] or saline vehicle at 24 h. Serum
      cytokine levels were measured by enzyme-linked immunosorbent assay (IL-10, IL-6)
      or WEHI bioassay [tumor necrosis factor (TNF)], and survival was determined at 5
      days. The role of IL-10 on the TNF response and survival was examined in a subset
      of mice given mouse anti IL-10 IgM (25 mg/kg intraperitoneally) 2 h prior to the
      initial insult. Survival after LPS was significantly different (P < 0.05) among
      the treatment groups (IR, 64%; LAP, 55%; CTRL, 11%) and appeared to trend
      directly with the magnitude of the initial operation. The serum IL-10 levels in
      the IR and LAP groups were significantly increased 4 h after the initial insult
      and remained elevated at 24 h. Peak serum TNF levels after LPS were significantly
      lower in the IR and LAP groups. Administration of anti IL-10 IgM resulted in
      uniform mortality and a significant increase in the peak TNF levels after LPS
      administration for all initial treatment groups. Endogenous production of IL-10
      following laparotomy down-regulates the TNF response and improves survival after
      endotoxemia.

PMID- 10947161
TI  - Impact of polynitroxylated albumin (PNA) and tempol on ischemia/reperfusion
      injury: intravital microscopic study in the dorsal skinfold chamber of the Syrian
      golden hamster.
AB  - Nitric oxide-releasing drugs have been shown to reduce ischemia/reperfusion (I/R)
      injury by acting as radical scavengers. However, their therapeutic application is
      hampered by specific side effects and rapid bioreduction in vivo. The half-life
      and antioxidant activity of nitroxides may be enhanced by their covalent binding
      to human serum albumin, resulting in polynitroxyl albumin (PNA). Thus, PNA may
      represent a novel antioxidative drug. The objectives of this study were to
      elucidate 1) whether PNA is able to diminish I/R injury; 2) the most effective
      dose of PNA in vivo; and 3) whether the addition of the nitroxide tempol enhances
      and/or prolongs the effect of PNA. Experiments were performed using a 4-h
      tourniquet-induced ischemia model in the hamster dorsal skinfold chamber. In the
      first part, five groups (n = 6) of animals received an infusion of 1) 1% body
      weight (b.w.) saline (0.9%); 2) 0.5% b.w. albumin (20%); 3) 0.5% b.w. PNA (20%);
      4) 1% b.w. albumin (20%); and 5) 1% b.w. PNA (20%) 15 min prior to reperfusion.
      In the second part of the study, tempol (17 mg/mL) was added either to albumin or
      PNA (1:9), and 0.5% b.w. of this solution was infused (Group 6: tempol + albumin
      0.5% b.w.; Group 7: tempol + PNA 0.5% b.w.). Intravital fluorescence microscopy
      allowed for quantification of functional capillary density (FCD), leukocyte
      adherence, extravasation of fluorescein isothiocyanate-labeled Dextran and non
      viable (Propidium-positive) cell count prior to ischemia and 0.5 h, 2 h, and 24 h
      after reperfusion. PNA and--to a lesser extent albumin--effectively reduced
      postischemic microvascular perfusion failure, leukocyte adhesion, and tissue
      injury. PNA was most effective in the dose 1% b.w. Although free oxygen radical
      scavenging seems to be an underlying mechanism leading to the beneficial effects
      of PNA on I/R injury, hemodilution and known radical scavenging properties of
      pure albumin contribute in part to the observed effects. Although the combination
      of tempol and PNA revealed further short-term effects on microvascular perfusion
      and leukocyte adhesion, it did not result in a long-term improvement of tissue
      injury.

PMID- 10947162
TI  - Defective lipopolysaccharide-dependent ERK 1/2 activation in endotoxin tolerant
      murine macrophages is reversed by direct protein kinase C stimulation.
AB  - Lipopolysaccharide (LPSp) pretreatment inhibits TNF secretion in endotoxin
      tolerant macrophages via alterations in signal transduction pathways of LPS
      activation (LPSa). Protein kinase C inhibitors prevent TNF release in response to
      LPSa and direct protein kinase C activation with phorbol myristate acetate (PMA)
      restores TNF secretion after LPSp. In the current experiments the effect of
      protein kinase C modulation on LPSa-stimulated ERK 1/2 activation was
      investigated. Murine macrophage TNF production was determined after stimulation
      with 100 ng/mL of LPSa, +/- 24 h pretreatment with 10 ng/mL of LPSp. Direct
      protein kinase C activators (PMA or indolactam) or inhibitors (H7 or
      bisindolylmaleimide) were added 1 h before LPSa. Diphosphorylated ERK 1/2 was
      assayed after LPSa stimulation by Western blot. LPS tolerance after LPSp was
      characterized by inhibition of LPSa-stimulated TNF and accompanied by impaired
      ERK 1/2 activation by LPSa. Protein kinase C activation with PMA or indolactam
      restored ERK 1/2 activation and TNF secretion. Inhibition of protein kinase C
      with H7 or bisindolylmaleimide prevented TNF secretion and ERK 1/2 activation by
      LPSa. These findings suggest that both ERK 1/2 and protein kinase C are required
      for TNF production in nontolerant macrophages and that LPS tolerance may be
      associated with an inability to phosphorylate ERK 1/2.

PMID- 10947163
TI  - Intraabdominal sepsis down-regulates transcription of sodium taurocholate
      cotransporter and multidrug resistance-associated protein in rats.
AB  - Hepatic dysfunction in sepsis is characterized by hyperbilirubinemia and
      intrahepatic cholestasis. We hypothesize that sepsis causes decreased hepatic
      transcription of the bile acid transporter sodium taurocholate cotransporter
      (Ntcp) and the organic anion transporter multidrug resistance-associated protein
      (Mrp2) and that interleukin (IL)-6 is important in the down-regulation of Ntcp
      and Mrp2 expression. Male Sprague-Dawley rats underwent induction of mild,
      nonlethal sepsis by cecal ligation and single puncture (CLP) or fulminant sepsis
      by cecal ligation and double puncture (2CLP). Hepatic transcription of Ntcp and
      Mrp2 rapidly decreased after CLP or 2CLP. Seventy-two hours later, transcription
      was 60% of baseline in CLP and 14% of baseline in 2CLP. Serum bilirubin was
      elevated from 24 h onward and cholestasis was observed on fixed liver specimens
      at 24, 48, and 72 h after 2CLP but not after CLP. Steady-state Ntcp and Mrp2 mRNA
      was decreased in IL-6-treated cultured hepatocytes and in normal rats given 1
      mg/kg intravenous IL-6. We conclude that 1) Ntcp and Mrp2 transcription is down
      regulated transiently after CLP and persistently after 2CLP; 2) 2CLP results in
      hyperbilirubinemia and cholestasis, in part due to persistently decreased
      transcription of Ntcp and Mrp2; and 3) altered Ntcp and Mrp2 transcription is
      mediated in part by IL-6.

PMID- 10947164
TI  - Differential regulation of c-jun expression in liver and lung of mice after
      thermal injury.
AB  - In addition to skin injury, burns may also damage distant organs. Understanding
      the mechanisms of distant organ injury will substantially improve the survival of
      burn patients. Transcription factors are the major regulators of gene expression
      in response to most types of injury. C-Jun, which is a part of the activator
      protein-1 transcription factor complex, is one of the major immediate-early
      response genes, which is rapidly induced after injury. The expression of c-Jun in
      mouse liver and lung at different time points (3 h to 29 days) after thermal
      injury was examined by using Reverse Transcription-Polymerase Chain Reaction (RT
      PCR), Western blot, and immunohistochemistry. Rapid induction of c-Jun mRNA and
      protein was observed in the liver 3 h after an 18% TBSA burn. C-Jun expression
      returned to basal levels within 3 days after injury. In contrast to the up
      regulation observed in liver, lungs from the same mice expressed c-Jun
      constitutively throughout the same time points. The finding that thermal injury
      leads to up-regulation of c-Jun in liver but not lungs suggests that either the
      liver has a lower threshold for early response to injury or that different
      cellular events exist when each organ is stressed.

PMID- 10947165
TI  - Massive chemokine transcription in acute renal failure due to polymicrobial
      sepsis.
AB  - Abdominal sepsis and septic shock are still major causes of mortality in
      intensive care units (ICU). Acute renal failure (ARF) is one of the hallmarks
      encountered in septic shock. The pathophysiological alterations leading to ARF
      are poorly understood. A novel murine model of polymicrobial sepsis (colon
      ascendens stent peritonitis [CASP]) was used to investigate functional renal
      parameters, renal chemokine transcription levels, and recruitment of inflammatory
      leukocytes in septic ARF. CASP was induced by inserting a 14-gauge stent into the
      colon ascendens of C57BL/6 mice, generating a septic focus resulting in
      polymicrobial sepsis. Mice were monitored for urine output and serum azotemia.
      Kidneys were harvested for analysis of leukocyte infiltration by
      immunohistochemistry and chemokine gene expression by RNase protection assay (3,
      6, 12, and 18 h). CASP, but not sham-CASP, resulted in anuria immediately after
      surgery and in elevated serum creatinine and BUN detected 18 h after CASP
      surgery, confirming acute renal failure. Progressive induction of chemokine gene
      expression was observed for IP-10, MIP-2, MIP-1alpha, MIP-1beta, MCP-1, and
      RANTES peaking at 12 h with subsequent decrease. Immunohistochemistry revealed an
      accumulation of neutrophils and monocytes which had adhered to the renal vascular
      endothelium. Thus, acute renal failure in sepsis is accompanied by a marked
      upregulation of chemokines of the CC and CXC group within the kidney.

PMID- 10947166
TI  - Interleukin-1beta alters the oxygen delivery-oxygen consumption relationship in
      rabbits by increasing the slope of the supply-independent line.
AB  - When systemic oxygen delivery (DO2) is reduced, oxygen consumption (VO2) is
      maintained until a critical level is reached (DO2crit). Sepsis is thought to
      shift DO2crit to the right and lengthen the supply-dependent portion. We tested
      the effect of interleukin (IL)-1beta, which is one of the key cytokines related
      to sepsis, on the DO2-VO2 relationship. Fifteen rabbits were subjected to
      stepwise cardiac tamponade to reduce DO2 to 10% by inflating a handmade balloon
      placed into the pericardial sac. Seven rabbits were given 10 microg/kg of IL
      1beta intravenously (IL-1beta group) prior to the graded cardiac tamponade. The
      remainder received saline alone (control group). The DO2-VO2 relationship was
      analyzed by the dual-line method. IL-1beta significantly decreased mean arterial
      pressure (65 +/- 11 mmHg from baseline 85 +/- 7 mmHg) without altering cardiac
      output. The IL-1beta group showed significantly steeper supply-independent line
      slopes than did the control group (0.19 +/- 0.02 vs. 0.11 +/- 0.02,
      respectively), which resulted in a DO2crit shift to the left (IL-1beta group, 8.7
      +/- 1.7 ml/kg x min vs. control, 11.7 +/- 0.7 ml/kg x min). The IL-1beta group
      also showed greater PO2 and plasma lactate levels in the portal vein than did the
      control group. These results indicate that IL-1beta impairs systemic oxygen
      uptake even before VO2 becomes supply-dependent, presumably due to
      maldistribution of the blood flow including the splanchnic circulation.

PMID- 10947168
TI  - Depletion of lactate by dichloroacetate reduces cardiac efficiency after
      hemorrhagic shock.
AB  - We have demonstrated previously that dichloroacetate (DCA) treatment in rodents
      ameliorates, via activation of the pyruvate dehydrogenase complex, the
      cardiovascular depression observed after hemorrhagic shock. To explore the
      mechanism of this effect, we administered DCA in a large animal model of
      hemorrhagic shock. Mongrel hounds were anesthetized with 1.5% isoflurane and were
      measured for hemodynamics, myocardial contractility, and myocardial substrate
      utilization. They were hemorrhaged to a mean arterial pressure of 35 mm Hg for 90
      min or until arterial lactate levels reached 7.0 mM (1137 +/- 47 mL or 49 +/- 2%
      total blood volume). Animals were chosen at random to receive DCA dissolved in
      water or an equal volume of saline at the onset of resuscitation. Two-thirds of
      the shed blood volume was returned immediately after giving an equivalent volume
      of saline. Two hours after the onset of resuscitation, mean arterial pressure was
      not different between DCA and control groups (79 +/- 3 vs. 82 +/- 3 mm Hg,
      respectively). Arterial lactate levels were significantly reduced by DCA (0.5 +/-
      0.06 vs. 2.0 +/- 0.2 mM). However, DCA treatment was associated with a decreased
      stroke volume index (0.56 +/- 0.06 vs. 0.82 +/- 0.08 mL/kg/beat) and a decreased
      myocardial efficiency (19 vs. 41 L x mm Hg/mL/100 g tissue). During resuscitation
      by DCA, myocardial lactate consumption was reduced (21.4 +/- 3.7 vs. 70.7 +/-
      16.3 micromole/min/100 g tissue) despite a three-fold increase in myocardial
      pyruvate dehydrogenase activity, while free fatty acid levels actually began to
      rise. Although increased lactate oxidation should be beneficial during
      resuscitation, we propose that DCA treatment led to a deprivation of myocardial
      lactate supply, which reduced net myocardial lactate oxidation, thus compromising
      myocardial function during resuscitation from hemorrhagic shock.

PMID- 10947167
TI  - Non-protein thiols flux to S-nitrosothiols in endothelial cells: an LPS redox
      signal.
AB  - Lipopolysaccharide (LPS) injures blood vessels by activating pathways in the
      endothelium that lead either to cell survival and proliferation or apoptosis. It
      has been suggested that these outcomes are determined when reactive oxygen and
      nitrogen intermediates oxidize low molecular weight non-protein thiols (NPSHs)
      such as glutathione (GSH) and cysteine (Cys), which serve as major intracellular
      reducing agents. The oxidoreduction of NPSHs could be an important redox signal
      if it were shown to occur rapidly following injury. Towards that end, cultured
      bovine aortic endothelial cells were stained with the thiol fluorescent probe,
      monobromobimane (MBB). Most of the acid extractable MBB-reactive adducts are GSH
      (approximately 90%) and Cys (approximately 90%). Within 1 min of LPS exposure, 50
      70% of the MBB-reactive NPSHs are consumed without evidence for concomitant net
      generation of superoxide, hydrogen peroxide, singlet oxygen, or glutathione
      disulfide (GSSG). Although LPS induces an increased rate of thiol-disulfide
      exchange, the slight increase does not explain the magnitude of NPSH consumption.
      Within the first 10 min of recovery from LPS exposure, the MBB-reactive NPSH
      fluorescence returns at or slightly above baseline values. When HgCl2 was added
      to the acid extract, one mole of S-nitrosothiol oxidizing equivalent was found
      for every mole of MBB-reactive NPSH consumed. It is suspected that the rapid flux
      of MBB-reactive NPSHs and Hg2+-inducible oxidants reflects transition of GSH to
      GSNO (S-nitrosoglutathione) and could be an important redox signal in endothelial
      cells exposed to LPS.

PMID- 10947169
TI  - Lactate improves cardiac efficiency after hemorrhagic shock.
AB  - This study was undertaken to examine the role of lactate on cardiac function and
      metabolism after severe acute hemorrhagic shock. Anesthetized, nonheparinized
      rats were bled to a mean arterial pressure of 25-30 mm Hg for 1 h; controls were
      not bled. Their hearts were removed, and cardiac work and efficiency (work/oxygen
      consumption) were measured in the isolated working heart mode for 60 min. The
      hearts were perfused with one of five substrate combinations: 1) glucose (11 mM),
      2) glucose + 0.4 mM palmitate, 3) glucose + 0.4 mM palmitate + 8.0 mM lactate, 4)
      glucose + 1.2 mM palmitate, or 5) glucose + 1.2 mM palmitate + 8.0 mM lactate.
      After perfusion, hearts were freeze-clamped, and tissue contents of free coenzyme
      A (CoA), acetyl CoA, and succinyl CoA were measured, as was myocardial pyruvate
      dehydrogenase (PDH) activity. The addition of 8.0 mM lactate significantly
      improved cardiac work in shocked hearts perfused with 0.4 mM palmitate and
      increased cardiac efficiency in the presence of either 0.4 mM or 1.2 mM
      palmitate. Compared to control hearts, shocked hearts exhibited a 20-30% decrease
      in PDH activity. Shocked hearts perfused with lactate demonstrated no increase in
      acetyl CoA content but did have a significant increase in tissue succinyl CoA
      compared to control hearts perfused with lactate or shocked hearts perfused
      without lactate. In the heart recovering from severe hemorrhagic shock, lactate
      improves cardiac efficiency in the presence of free fatty acids, possibly by a
      anaplerosis of the tricarboxylic acid cycle.

PMID- 10947170
TI  - Effect of intravenous infusion of omega-3 and omega-6 lipid emulsions on equine
      monocyte fatty acid composition and inflammatory mediator production in vitro.
AB  - The effect of intravenous administration of lipid emulsions enriched with omega-3
      (n3) and omega-6 (n6) fatty acids on equine monocyte phospholipid fatty acid
      composition and the synthesis of inflammatory mediators in vitro was evaluated.
      In a randomized crossover design, horses were infused intravenously with 20%
      lipid emulsions containing n3 or n6 fatty acids. Monocytes were isolated from the
      horses before and 0 h, 8 h, 24 h, and 7 days after lipid infusion. Monocyte fatty
      acid analysis demonstrated incorporation of the parenteral n3 and n6 fatty acids
      in monocyte phospholipids immediately after infusion, with changes in the fatty
      acid composition persisting for up to 7 days after infusion. In vitro production
      of the inflammatory mediators thromboxane B2/thromboxane B3 (TXB(2/3)) and tumor
      necrosis factor-alpha (TNFalpha) by peripheral blood monocytes was diminished by
      n3 lipid infusion and was unchanged or increased by n6 lipid infusion. The
      results of this study demonstrate that short-term infusions of n3 and n6 fatty
      acid-enriched lipid emulsions alter the fatty acid composition of equine monocyte
      phospholipids and modify the inflammatory response of these cells in vitro. These
      results also support further investigation into the use of parenteral n3 fatty
      acids as part of the supportive therapy of patients with multiple organ
      dysfunction (MODS) or systemic inflammatory response syndrome (SIRS).

PMID- 10947171
TI  - The cytoprotective role of lipopolysaccharide-induced nitric oxide against liver
      damage during early phase of endotoxemia in rats.
AB  - Lipopolysaccharide (LPS)-induced endotoxemia produces nitric oxide (NO); however,
      the role of the NO during endotoxemia is still controversial. The aim of this
      study was to investigate a role of LPS-induced NO during the early phase of
      endotoxemia. Wistar rats were intraperitoneally injected with saline or LPS at
      various doses (0.001, 0.01, or 5 mg/kg), and intra-abdominal NO concentration was
      determined by chemiluminescence before and after LPS administration at indicated
      times (1, 2, 6, 10, and 18 h). Serum aspartate aminotransferase and alanine
      aminotransferase levels were determined and histological examination was
      performed 10 h after LPS administration to assess liver damage. N(G)-nitro-L
      arginine-methyl ester (L-NAME), a nonselective inhibitor of NO synthase, was used
      to investigate the possible roles of NO during LPS-induced endotoxemia. The intra
      abdominal NO concentration was elevated within 2 h and reached a maximal level at
      10 h after low doses of LPS injection (0.001 and 0.01 mg/kg) while liver damage
      was not observed. After high-dose LPS (5 mg/kg) administration, liver damage was
      observed and intra-abdominal NO was elevated continuously until 18 h. A time
      course study revealed very similar patterns of intra-abdominal NO increase after
      the three different dose of LPS at each times points during the first 10 h.
      Pretreatment of L-NAME inhibited the intra-abdominal NO release and aggravated
      the liver damage caused by low doses (0.001 and 0.01 mg/kg) of LPS as well as
      high dose (5 mg/kg) of LPS. Therefore, NO, released during the first 10 h after
      LPS injection, may play a cytoprotective role in the liver.

PMID- 10947172
TI  - Prostaglandin E1 reduces ischemia/reperfusion injury by normalizing nitric oxide
      and superoxide release.
AB  - To test the effects of prostaglandin E1 on 2.5 h of ischemia followed by 2 h of
      reperfusion, continuous nitric oxide measurements (electrochemical) were
      correlated with intermittent assays of superoxide and peroxynitrite levels
      (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus
      muscle. Administering prostaglandin E1 (1 microg/kg) before or during
      ischemia/reperfusion caused normalization of the release of nitric oxide,
      superoxide, and peroxynitrite to slightly above preischemic levels. This pattern
      was dramatically different from that observed during ischemia/reperfusion alone,
      where nitric oxide concentration increased three times above its basal level.
      Normalization of constitutive nitric oxide synthase activity in the presence of
      prostaglandin E1 was associated with a significant reduction of superoxide and
      peroxynitrite production and subsequent reduction of ischemia/reperfusion injury.
      At 2 h of reperfusion, vasoconstriction associated with ischemia/reperfusion
      injury was eliminated, and edema was significantly mollified but still apparent.
      Prostaglandin E1 treatment does not directly inhibit constitutive nitric oxide
      synthase, like the inhibitor N(omega)-monomethyl-L-arginine. Some phenomenon
      associated with ischemia turns on endothelial constitutive nitric oxide synthase
      to start transforming L-arginine and oxygen into nitric oxide, but prostaglandin
      E1 seems to inhibit this phenomenon. Thus, essential local L-arginine pools are
      not depleted, and normal basal levels of essential nitric oxide are maintained,
      whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient
      constitutive nitric oxide synthase is prevented.

PMID- 10947173
TI  - Nitric oxide synthase and tissue injury.

PMID- 10947174
TI  - Hereditary persistent right oviduct in the chicken PNP/DO line.
AB  - Hereditary, persistent, right oviduct manifested in an inbred line (PNP/DO line)
      from the Fayoumi breed of chickens was investigated for form of expression and
      mode of inheritance. Females in the PNP/DO line have varying lengths of elongated
      right oviducts, besides the normal left ovary, and oviducts that generally
      possess, irrespective of their total length, regions similar to those normally
      observed in a left oviduct. Observations of embryos indicated that the existence
      of right oviduct in this line could be attributed to the slow regression of right
      Mullerian duct during the embryonic stage, and left-right asymmetry in female
      genital system is intrinsic in this line. Intracrosses of the PNP/DO line
      produced 93% of female embryos with persistent right Mullerian ducts at the next
      generation, and reciprocal crosses of the PNP/DO line and control strains
      produced 5 and 30% of female embryos with persistent right Mullerian ducts in the
      F1 and N2 generations, respectively. Mating results suggested that this mutant
      trait is controlled by two pairs of autosomal recessive genes with major effects
      and numerous loci that have minor effects. Thus, expression of this trait is due
      to the interaction of major loci and the background genotype.

PMID- 10947175
TI  - A review of the development of chicken lines to resolve genes determining
      resistance to diseases.
AB  - The resolution of genes that determine resistance to disease is described using
      chicken lines maintained at the Avian Disease and Oncology Laboratory (ADOL).
      This description includes a summary 1) of existing selected and inbred lines
      differing for resistance to viral-induced tumors, i.e., Marek's disease (MD) and
      lymphoid leukosis (LL), and of the use of inbred and line crosses to define
      relevant disease-resistant genes, e.g., TV, ALVE, B, R, LY4, TH1, BU1, and IGG1;
      2) of the development of TVB*/ALVE congenic lines to establish the affects of
      endogenous virus (EV) expression on resistance to avian leukosis virus (ALV), and
      methods to detect ALVE expression; 3) of the development of B congenic lines to
      define the influence of the MHC on MD resistance and vaccinal immunity, for
      producing B antisera, and for evaluating DNA sequences of Class I and II genes;
      and 4) of the current development of 6C.7 recombinant congenic strains (RCS) to
      define the role of non-MHC genes influencing susceptibility to MD and LL tumors,
      immune competence, and epistatic effects of genes. The procedures of pedigree
      mating, to avoid or maintain inbreeding, and of blood-typing, to ensure genetic
      purity of the lines, are also described.

PMID- 10947176
TI  - The effects of body weight and long ahemeral days on early production parameters
      and morphological characteristics of broiler breeder hens.
AB  - Shaver Starbro broiler breeder pullets were used to study the effect of day
      length (24 and 28 h) on egg production parameters and egg traits from 22 to 30 wk
      of age, and ovarian and morphological characteristics at 30 wk of age. Floor
      housed pullets were raised in a light-tight facility from 1 d of age until
      housing in individually illuminated cages at time of photostimulation (22 wk).
      Cages were equipped with hardware to monitor egg laying time. The photoschedule
      during rearing was 24 h light: 0 h dark for the first 3 d followed by 8 h light:
      16 h dark from 3 d to photostimulation. Body weight was monitored throughout the
      trial to maintain weights at targets set by Shaver Poultry Breeding Farms, Ltd.
      The experimental design was a 2 x 2 factorial with two day lengths [hemeral (24
      h) and ahemeral (28 h)] and two BW groups [high (HBW) and low BW (LBW)], with the
      LBW weighing 327 g less than the HBW birds at 22 wk of age. The hemeral
      photoschedule was 14 h light: 10 h dark, and the ahemeral photoschedule was 14 h
      light: 14 h dark. Differences in BW remained throughout the trial. Egg numbers
      were not increased by the 28-h day (24 h = 25.4 eggs; 28 h = 23.1 eggs). The 24-h
      hens laid more double-yolked eggs (0.9% of total egg production) than did the 28
      h birds (0.3%). Egg formation time was consistently longer for the 28-h hens
      (26.8 h at 25 wk of age and 25.8 h at 29 wk of age) compared with the 24-h hens
      (25.4 h at 25 wk of age and 24.8 h at 29 wk of age). Mean egg weight was higher
      for the 28-h birds (55.1 g) compared with the 24-h birds (53.0 g). Egg specific
      gravity was higher in eggs from the 28-h hens than eggs from the 24-h hens. Some
      of the increase in egg weight between the 28- and 24-h birds was due to shell
      weight. Absolute and proportional weights of the egg shell were 5.5 g and 10.0%
      of the total egg weight for the 28-h birds and 4.9 g and 9.3% for the 24-h birds,
      respectively. The 28-h hens had higher proportional breast muscle weight, smaller
      livers and oviducts, and lower ovary weight compared with the 24-h birds. The
      data indicated that, although egg size can be increased with the use of long
      ahemeral days early in lay, this result may be at the expense of egg numbers.
      Early in lay, follicular maturation rates are fast, and egg production may be
      limited to one ovulation per 28 h.

PMID- 10947177
TI  - Effect of dietary aspirin on ascites in broilers raised in a hypobaric chamber.
AB  - During the course of ascites development in broilers, many factors can interact
      to cause hypoxia. To counteract hypoxia, birds with ascites develop greatly
      increased hematocrit and red cell counts. Increasing hematocrits result in more
      viscous blood. Prostaglandins are involved in the regulation of constriction and
      dilation of pulmonary blood vessels and in the formation of blood clots. Dietary
      aspirin, a prostaglandin inhibitor, was used in an attempt to promote
      vasodilation and inhibit blood clotting in broilers, with the objective of
      determining the effect of aspirin on ascites progression. The experimental design
      consisted of two trials with a total of 1,360, 1-d-old male broiler chicks, which
      were placed at either local altitude (390 m above sea level) or in a hypobaric
      chamber that simulated an altitude of 2,900 m above sea level. At each elevation,
      five dietary treatments were employed: [control, 0.025% crystalline
      acetylsalicylic acid (aspirin), 0.05% aspirin, 0.10% aspirin, and 0.20% aspirin].
      Bird and feed weights were recorded weekly. At the end of 5 wk, blood samples and
      organ weights were collected, and all birds were examined for signs of ascites.
      In both trials, birds raised at high altitudes were significantly lighter, had a
      higher incidence of ascites, and had differences in hematology, compared with
      birds raised at local elevation. Only in Trial 2, however, did dietary aspirin
      appear to have any effect on ascites incidence. At the 0.20% aspirin level, a
      reduction in ascites incidence approached significance compared with controls
      (34% vs. 56%, P < or = 0.06). Unfortunately, birds fed 0.20% aspirin also were
      significantly (P < or = 0.01) lighter than controls. Because slowing growth rate
      is known to reduce ascites, this decrease in BW may have been partially
      responsible for any beneficial effect on ascites development and progression
      obtained through feeding aspirin.

PMID- 10947178
TI  - Dietary linoleic acid divergently affects immune responsiveness of growing layer
      hens.
AB  - The effects of linoleic (LA)- and linolenic acid (LNA)-enriched diets on humoral
      and in vivo cellular immune responses to keyhole limpet hemocyanin (KLH)
      dinitrophenyl (DNP) and Mycobacterium butyricum were studied in growing layer
      hens. Pullets were fed one of three diets: a control, LA enriched, or LNA
      enriched. Pullets were assigned to one of three immunization treatments: KLH-DNP,
      M. butyricum, or PBS. The LA-enriched diet enhanced the antibody response to KLH
      in pullets immunized with KLH-DNP. On the other hand, the antibody response to M.
      butyricum in M. butyricum-immunized birds was decreased by feeding an LA-enriched
      diet. In vitro lymphocyte proliferation in the presence of Concanavalin A was
      affected by the interaction between diet and immunization. Neither cutaneous
      hypersensitivity to KLH nor to M. butyricum was affected by the diet. The BW gain
      before immunization was not affected by the diet, but after immunization, the LA
      enriched diet enhanced growth in birds immunized with M. butyricum. Diets had
      various effects on organ weights. We concluded that dietary linoleic acid
      enrichment of the diet has an antigen-dependent divergent effect on the antibody
      response. The dietary LNA effect on the antibody response is less pronounced and
      is opposite to that of the LA effect.

PMID- 10947179
TI  - In vivo gene electroporation confers strong transient expression of foreign genes
      in the chicken testis.
AB  - To attain foreign gene expression in vivo in the testis of living chickens,
      chloramphenicol acetyltransferase (CAT) and firefly luciferase reporter genes
      were transfected by electroporation (EP). Bioluminescence imaging indicated clear
      expression of the luciferase reporter gene localized in and around the injection
      site of the chicken testis. The CAT activity decreased sharply from 7 to 14 d
      posttransfection (P < 0.01) and remained low until 28 d. The presence of the self
      replication sequence of Epstein-Barr virus did not give significantly higher CAT
      gene expression over the 28-d posttransfection. The results suggest that in vivo
      gene EP confers strong, likely transient, foreign gene expression in the testis
      of living chickens.

PMID- 10947180
TI  - Effects of dietary potassium supplementation for growing turkeys on leg weakness,
      plasma potassium concentration, and selected blood variables.
AB  - The objectives of this research were to observe the effects of increased K in the
      diets of growing tom turkeys from 6 to 18 wk of age on body weight, feed-to-gain
      ratio, and leg weakness; to study the effects of time and temperature of blood
      storage after sampling and before centrifugation on plasma K concentration; and
      to evaluate plasma creatine kinase activity as an indicator of leg weakness. Male
      Nicholas White turkeys were fed corn-soybean meal based starter and grower diets
      from 1 d to 6 wk of age. At this time, each of three dietary treatments was
      assigned randomly to three pens of toms, 30 toms per pen. The dietary treatments
      consisted of 1) corn-soybean meal control (control) diets, 2) corn-soybean meal
      diets supplemented with 25% more K than the control diets contained (Mod K), and
      3) corn-soybean meal diets supplemented with 50% more K than the control diets
      (High K). Potassium carbonate was used as the source of supplemental K for the
      Mod K and High K diets. Calculated K concentrations of the control diets fed from
      6 to 9, 9 to 12, 12 to 15, and 15 to 18 wk were 0.84, 0.74, 0.57, and 0.54%,
      respectively. Results of laboratory analysis of the diets agreed closely with the
      calculated values. By 12 wk, toms fed the High K diets weighed less (P = 0.018)
      than toms fed the control diets, and this difference was still evident at 18 wk
      (P = 0.013), even though the High K groups were changed to the control diets at
      12 wk. Toms fed the Mod K diets also tended to weigh less at 16 and 18 wk than
      those fed the control diets, however, the diet effect at the latter time was not
      significant (P > 0.05). There were no consistent effects of dietary K on feed
      efficiency. Total incidence of leg weakness at 12 wk was greater (P = 0.015)
      among toms fed Mod K and High K diets than for those toms fed the control diets.
      These results show that dietary K concentrations greater than those usually
      present in corn-soybean meal based diets for growing turkeys should be avoided.
      Increases in dietary K concentrations were associated with increases in plasma K
      concentration. Storage of blood after sampling and before centrifugation
      decreases the plasma concentration of K. The decrease is minimized when ambient
      temperature of storage is decreased. Accordingly, blood should be centrifuged
      immediately after sampling for accurate measurement of plasma K concentration.
      Plasma creatine kinase activity is not a good indicator of associated leg
      weakness unless physical activity and stress can be controlled before blood
      sampling.

PMID- 10947181
TI  - Nutritional evaluation of soybean meals varying in oligosaccharide content.
AB  - Three conventional soybean meals (CSBM) and five low-oligosaccharide soybean
      meals (LOSBM) were evaluated. Meals were prepared by solvent-extracting flakes
      from generic soybean lines and soybean lines genetically modified to contain
      varying oligosaccharide content. The mean raffinose, stachyose, and galactinol
      levels in the CSBM were 0.58, 3.23, and 0%, respectively. The mean (range)
      raffinose, stachyose, and galactinol levels in the LOSBM were 0.08 (0.03 to
      0.17%), 0.42 (0.04 to 1.08%), and 0.104 (0 to 0.24%), respectively. The crude
      fiber, fat, and ash contents of all SBM were similar, whereas the CP and sucrose
      contents of the LOSBM were slightly higher than the CSBM. The effect of SBM type
      on digesta passage rate, dry matter digestibility, and TMEN was assessed in
      conventional and cecectomized roosters using a precision-fed rooster assay (8 x 2
      factorial design). Quantitative collection of excreta for 4, 8, 12, 16, 20, 24,
      and 48 h postfeeding indicated little or no effect of SBM type on digesta passage
      rate. The dry matter digestibility and TMEN values for the SBM were lower for
      cecectomized roosters compared with conventional roosters (P < 0.05), and there
      was no significant SBM x bird type interaction. The mean TMEN values (kcal/kg DM)
      for the CSBM and LOSBM were 2,739 and 2,931, respectively, which was a difference
      of 7% (P < 0.05). The two LOSBM with the lowest total raffinose, stachyose, and
      galactinol levels (0.07% and 0.25%) had average TMEN values that were 9.8% (P <
      0.05) higher than their respective genetic controls. Digestibilities of raffinose
      and stachyose were much higher (P < 0.05) in conventional roosters than in
      cecectomized roosters. The results of this study indicated that the TMEN of LOSBM
      was higher than that of CSBM.

PMID- 10947182
TI  - Tissue-specific fatty acid and alpha-tocopherol profiles in male chickens
      depending on dietary tuna oil and vitamin E provision.
AB  - The beneficial health-promoting effects of the long-chain polyunsaturated fatty
      acids (PUFA) of the n-3 series make them important constituents of human and
      animal diets. The effects of tuna oil or a combination of tuna oil with an
      increased level of vitamin E on the fatty acid profile and vitamin E distribution
      in tissues taken from cockerels were studied. Male chickens (Ross broiler
      breeders), penned on white wood shavings, were allocated into one of three groups
      with 12 birds per group and were fed from 10 wk of age on a commercial diet
      supplemented with 3% corn oil (control) or with 3% Tuna orbital oil (TO). Vitamin
      E was added at the rate of 40 mg/ kg, except in the third group in which the
      birds received a diet containing TO (3%) supplemented with 160 mg/kg vitamin E
      (TO+E). At 72 wk of age, the cockerels were killed, and tissues (liver, testes,
      heart, lung, kidney, spleen, thigh muscle, pancreas, internal fat, cerebellum,
      and cerebrum) were dissected for lipid and vitamin E analyses. Inclusion of TO in
      the cockerel diets significantly (P < 0.01) increased docosahexanoic acid (DHA)
      proportions in the major lipid fractions of the tissues with the brain being more
      resistant to lipid manipulation compared with the other tissues. Tissue
      enrichment with DHA took place at the expense of a decrease of n-6 PUFA. In the
      DHA-enriched tissues, vitamin E level decreased (P < 0.05), and susceptibility to
      peroxidation (TBARS accumulation) significantly (P < 0.01) increased. High
      vitamin E supplementation (160 mg/kg) in combination with TO prevented decrease
      of alpha-tocopherol concentration in the tissues and normalized or even increased
      their resistance to lipid peroxidation. There was tissue-specificity in response
      to dietary vitamin E supplementation; the liver was most responsive and the
      cerebellum was most resistant to vitamin E manipulation.

PMID- 10947183
TI  - Reevaluation of nonphytate phosphorus requirement of growing pullets with and
      without phytase.
AB  - An experiment was conducted to re-evaluate the nonphytate phosphorus (NPP)
      requirement of growing pullets and to determine to what extent this requirement
      could be reduced by phytase. Six diets in a 3 x 2 factorial design were used. The
      pullets of the control group (T1) were fed a sequence of 0.4-0.35-0.3% NPP for
      the age periods of 0 to 6, 6 to 12, and 12 to 18 wk, respectively, according to
      NRC (1994) recommendation. The NPP level was reduced by an increment of 0.1% in
      each phase in T2 and T3. The pullets of T4 to T6 were fed similar NPP levels to
      T1 to T3, respectively, with 300 units phytase/kg diet. From 18 to 30 wk of age,
      the pullets on all growing regimens were fed a layer diet with 0.4% NPP. Records
      were maintained for BW and feed intake during the growing period and for egg
      production during the laying period. Blood and tibia samples were taken at 6, 12,
      and 18 wk of age for determining plasma P, tibia weight, and tibia ash. Two
      digestion trials were conducted at Weeks 5 and 18 for determining total P
      excretion. Body weights at 18 wk and feed intake for the period of 0 to 18 wk
      were not different from the control for pullets fed the two lower NPP regimens (P
      > 0.05). Phytase had a favorable effect on BW at 18 wk (P = 0.0539) and feed
      intake for the period of 0 to 18 wk (P < 0.05). Plasma P was lower for pullets
      fed the least NPP than for those fed the control NPP regimen only at 6 wk of age
      (P < 0.05). Bone quality measurements at 6, 12, and 18 wk of age were not
      different for pullets fed various NPP regimens (P > 0.05). Phytase, for the most
      part did, not have an effect on plasma P and bone quality (P > 0.05). Total P
      intake and total P excretion (mg/bird per day) were reduced due to lowering the
      dietary NPP in both digestion trials (P < 0.05). Phytase did not have an effect
      on daily total P intake or excretion. Production and specific gravity were not
      influenced by NPP regimens used during the growing period. Specific gravity for
      the entire experiment was greater for pullets fed phytase (P < 0.05). The results
      indicated that the lowest NPP regimen in the absence of phytase was adequate to
      support performance of pullets, and due to this, it was not possible to determine
      the effect of phytase in diminishing the P need of growing pullets.

PMID- 10947184
TI  - Evaluation of the isoleucine requirement of the commercial layer in a corn
      soybean meal diet.
AB  - An experiment was conducted with Hy-Line W36 hens to evaluate their Ile
      requirement in a corn-soybean meal diet. Five experimental diets were fed with
      Ile levels of 0.61, 0.58, 0.55, 0.52, and 0.49%. Supplemental amino acids (AA)
      were added to ensure that Ile was the first-limiting AA. Two diets with 0.55 and
      0.52% Ile were also fed with higher levels of supplemental AA. A positive control
      (0.67% Ile) with only Met supplementation was fed, which had previously been
      shown to support maximum performance. All levels of Ile addition significantly
      increased egg production (EP), egg weight (EW), and egg contents (EC). Broken
      line regression indicated a daily Ile requirement of 589.2, 601.2, and 601.4 mg
      per day for EP, EW, and EC, respectively, which indicated a requirement of 12.6
      mg Ile per gram of EC.

PMID- 10947185
TI  - Evaluating the efficacy of enzyme preparations and predicting the performance of
      leghorn chicks fed rye-based diets with a dietary viscosity assay.
AB  - We studied whether a single-step dietary viscosity assay could be used to
      evaluate the efficacy of an enzyme when added to a poultry diet. The results
      demonstrated a linear relationship between the log of the dietary viscosity
      change in vitro, as determined with the new assay and the log of the enzyme
      activity (xylanase) added to a rye-based diet. The sensitivity of the dietary
      viscosity assay was high, as little as 0.19 U of xylanase per gram of diet could
      be detected. In addition, there was a high correlation (r > or = 0.97; P < 0.005)
      between chick performance and the log of the amount of enzyme added to the diet
      or the log of its viscosity change in rye-based diets that contained different
      amounts of xylanase, as determined by the in vitro dietary viscosity assay.
      Further, the dose response data from the dietary viscosity assay, when
      incorporated into a log-linear model that we developed, was able to distinguish
      between the efficacy of two enzymes with regards to their ability to hydrolyze
      the viscosity factor in rye grain. Therefore, it was possible to accurately
      evaluate the efficacy of enzyme preparations in a rye diet and to predict chick
      performance using the new assay in conjunction with a model equation.

PMID- 10947186
TI  - Fatty acid determination in chicken egg yolk: a comparison of different methods.
AB  - Four different methods (direct-methylation, saponification, chloroform-methanol
      extraction, and postextraction saponification) were compared to determine the
      fatty acids in egg yolk. About 50 mg of pooled egg yolk samples, with C23:0 as an
      internal standard, was used for all assays. No difference (P > 0.05) was observed
      among the four methods for C17:0, C18:0, C18:1, C20:1, C18:2n-6, and C22:6n-3
      content of egg yolk. Direct saponification resulted in a lower (P < 0.05) content
      of C14:0, C16:1, C18:3n-3, and C20:4n-6. Fatty acids at less than 0.5%, such as
      C15:0 and C14:1, were not detectable in the direct saponification method. The
      total saturated, monounsaturated, or polyunsaturated fatty acids did not differ
      (P > 0.05) among the four methods. Direct methylation of egg yolk resulted in
      lower variability than other methods and is fast and economic for determining egg
      fatty acid composition.

PMID- 10947187
TI  - Immunolocalization analysis of transforming growth factor-beta1 in the growth
      plates of broiler chickens with high and low incidences of tibial
      dyschondroplasia.
AB  - Immunolocalization of transforming growth factor-beta1 (TGF-beta1) was determined
      in growth plates of two lines of broiler chickens with low and high incidences of
      tibial dyschondroplasia (TD). Ultrathin sections of growth plates from each line
      were treated with a polyclonal antibody specific for TGF-beta1, followed by
      colloidal gold-labeled protein A. Immunolocalization for TGF-beta1 was observed
      in chondrocytes of all zones of growth plates of low and high TD incidence lines.
      However, immunolocalization in extracellular matrix was restricted to the
      hypertrophic zones of both lines. In the hypertrophic zone of low TD incidence
      line, immunolocalization of TGF-beta1 in the extracellular matrix adjacent to
      collapsed cartilage canals (matrix streaks) was significantly greater than
      immunolocalization between patent cartilage canals. A similar increase was not
      observed in the high TD incidence line. Results indicate that chondrocytes of all
      zones of the growth plate contain TGF-beta1 but do not release it into
      extracellular matrix until hypertrophy has occurred. Greater concentrations of
      TGF-beta1 adjacent to collapsed cartilage canals may play a role in controlling
      angiogenesis and directing invasion of mineralized hypertrophic cartilage by
      metaphyseal blood vessels. A low concentration of TGF-beta1 in the extracellular
      matrix adjacent to collapsed cartilage canals of the high TD incidence line may
      be a factor in limiting vascular invasion of dyschondroplastic cartilage of TD
      lesions.

PMID- 10947188
TI  - Beta1 integrin expression during normal and low score normal avian myogenesis.
AB  - Skeletal muscle development is, in part, regulated by myoblast-extracellular
      matrix interactions mediated by the transmembrane integrin family of
      heterodimeric receptors. The avian genetic muscle weakness, low score normal
      (LSN), exhibits modified myotube and sarcomere structure that may be associated
      with altered integrin expression. Protein expression of the beta1 integrin
      subunit was measured during normal and LSN Pectoralis major muscle development at
      14, 16, and 18 d of embryonic development, and 1 d and 1 and 6 wk posthatch.
      During embryonic development, integrin expression was downregulated. However, by
      1 wk posthatch, integrin levels were upregulated and remained elevated through 6
      wk posthatch. This pattern was observed in both normal and LSN muscle
      development. Overall, beta1 integrin levels were lower in the LSN P. major
      muscle. In normal and LSN satellite cell cultures, beta1 integrin expression was
      low during proliferation. In early differentiation, beta1 integrin expression
      increased and was then downregulated. As observed in the muscle extracts, LSN
      beta1 integrin expression was significantly lower during differentiation. These
      results suggest that the regulation of beta1 integrin expression is critical to
      the progression of myogenesis, and, during LSN myogenesis, decreased expression
      of beta1 integrin may be associated with modifications in muscle structure.

PMID- 10947189
TI  - Aqueous apple flavoring in breast muscle has physical, chemical, and sensory
      properties similar to those of phosphate-marinated controls.
AB  - Marinades containing 0, 0.4, 0.8, and 1.2% apple flavoring were examined to
      determine the effect of an aqueous apple flavoring on the quality and sensory
      characteristics of boneless, skinless chicken breast. Marinade pickup and purge
      loss increased significantly with an increase of apple flavoring in marinades.
      Incorporation of apple flavoring in the marinades did not affect cook loss of the
      treatments, except for breast marinated in 1.2% apple flavor, which had higher
      cook loss. Apple flavoring did not affect final product yield of marinated
      breast. Shear values were similar for all treatments except marinades with 0.8%
      apple flavoring, which had lower shear values. Participants detected increases in
      fruity flavor with an increase of apple flavoring in the marinade. Products
      containing no apple flavoring were rated as "like moderately" to "like slightly."
      Products with 0.4% apple flavoring were rated "like slightly," and degree of
      liking declined to "neither like nor dislike" as apple flavoring increased.
      Incorporation of acceptable levels of apple flavoring is limited to 0.4%.

PMID- 10947190
TI  - Relating quality characteristics of aged eggs and fresh eggs to vitelline
      membrane strength as determined by a texture analyzer.
AB  - The TA-XT21 texture analyzer (TA) was used to evaluate vitelline membrane
      strength (VMS). Fresh and aged (1 wk at 25 C) eggs (n = 48 eggs x 2 replications)
      were evaluated. Fresh and aged eggs were further divided into two groups of yolk
      only or whole egg (with intact albumen). Yolk index, Haugh units, pH, broken-out
      egg weights, VMS, yolk viscosity, and scanning electron microscopy (SEM) images
      were evaluated. Results from the TA indicated a decrease in VMS in aged eggs
      compared to fresh eggs and in yolk-only eggs compared to whole eggs. The SEM
      images indicated a loss of structural integrity in aged eggs as compared to fresh
      eggs. As expected, aged eggs also had higher albumen and yolk pH, lower Haugh
      units, lower yolk index, and decreased viscosity compared to fresh eggs. There
      were no differences in broken-out egg weights or whole egg pH between fresh and
      aged eggs. As the yolk membrane strength increased, yolk index (r = 0.59) and
      Haugh units (r = 0.56) decreased, and yolk pH (r = -0.64) and albumen pH (r = 
      0.57) increased. The study suggests that the TA combined with the modified
      extrusion cell may be effective in determining VMS. In addition, yolk index,
      Haugh units, and yolk and albumen pH may be used to predict changes in VMS.

PMID- 10947191
TI  - Bacteriological and histological profile of turkeys condemned for cyanosis.
AB  - Canadian Food Inspection Agency (CFIA) has adopted the term cyanosis to describe
      a category of condemnation for poultry that is dark but has no other condemnable
      lesions. Two case-control studies (n = 30 pairs; n = 65 pairs) of 18-wk-old tom
      turkeys were conducted. A case was defined as a carcass condemned by the
      veterinary inspector for cyanosis, and a control carcass was one that passed
      inspection. Microbiological tests were conducted on samples of Pectoralis major
      and Gastrocnemius lacteralis. A modified Rappaport Vassiliadis medium was used
      for Salmonella, and a Petrifilm method was used to assess aerobic counts,
      coliform counts, and Escherichia coli. The Salmonella (qualitative) test was
      negative for all cases and controls, and there were no significant differences
      between the aerobic counts, coliform counts, and E. coli counts of case and
      control carcasses. Two pathologists conducted a blind histopathological study:
      there were no lesions compatible with those of septicemia-toxemia, as defined by
      CFIA and the USDA, nor any significant histopathological differences between the
      skin, P. major, G. lateralis, kidney, liver, spleen, small intestine, pancreas,
      lung, and heart of cases and controls. The inter-rater agreement between
      pathologists ranged from good to excellent (Kappa = 0.7 to 1.0). In the absence
      of important lesions and microbial contamination, carcasses with this color
      change alone should be suitable for human consumption.

PMID- 10947192
TI  - Efficacy of an herbal extract on the microbiological quality of broiler carcasses
      during a simulated chill.
AB  - Protecta II, an herbal extract on an NaCl carrier, was evaluated in a 30-min, 1 C
      simulated chill for its effectiveness of lowering microbial counts on broiler
      carcasses. Eighteen broiler carcasses were obtained from a local processing plant
      after final wash but before chill, placed into an insulated container, and
      transported to the research facility for treatment. Six plant run controls (PRC)
      were immediately bagged on return to the pilot plant, and a whole-carcass rinse
      was performed. The remaining carcasses were subjected to a 30-min chill (1 C) in
      tap water or a 2% solution of Protecta II, (n = 6 per treatment). After
      treatment, carcasses were rinsed with tap water and subjected to the whole
      carcass rinse procedure. All rinse diluents were microbiologically analyzed for
      total aerobes, coliforms, generic Escherichia coli, and Campylobacter. Six
      replications were analyzed on 6 different d for a total 36 carcasses per
      treatment and 36 PRC. The PRC carcasses had 3.7, 2.5, 2.1, and 2.0 log10 cfu/mL
      for total aerobes, coliforms, generic E. coli, and Campylobacter. Water treatment
      significantly reduced counts (2.6, 1.4, 0.7, and 0.9 log10 cfu/mL, respectively)
      when compared with the PRC. Protecta II treatment significantly reduced counts (P
      < 0.01) even further to counts of 0.06, 0.04, 0.01, and 0.00 log10 cfu/mL for
      total aerobes, coliforms, Campylobacter, and E. coli, respectively. Detectable
      levels of the monitored organisms were 1 cell/mL (log10 0) for the E. coli,
      coliforms, and total counts and 10 cells/mL (log10 1) for the Campylobacter.
      Microbial counts for carcasses treated with Protecta II would be considered too
      low to be detected (<1 cell/mL).

PMID- 10947193
TI  - The influence of transportation on turkey meat quality.
AB  - Previous research has indicated that antemortem stress factors can influence the
      development of pale, soft, and exudative (PSE) meat in swine as well as in
      turkeys. Such antemortem factors can include environmental temperatures, relative
      humidity, preslaughter handling practices, and transportation. However, the
      effect of transportation on meat quality of turkeys has not been extensively
      studied. Eighty Nicholas male turkeys (21 wk of age) were divided into two groups
      and were either transported in coops on a flatbed trailer for 3 h immediately
      prior to processing or processed without transportation. Breast muscle samples
      were collected for pH (0, 2, 24 h), L* value (2, 24 h), drip loss, and cook loss.
      Additionally, breast fillets were marinated and cooked to determine marination
      uptake, retention, and cook loss. The breast muscles from transported turkeys had
      significantly higher muscle pH at 0, 2, and 24 h; significantly lower L* values
      at 2 and 24 h; significantly higher marination retention (i.e., lower drip loss
      after marination); and significantly lower cook loss in the marinated fillets
      compared with fillets of the nontransported turkeys. There were no significant
      differences in drip loss and cook loss of the nonmarinated fillets or the
      marination uptake percentage between the transported and nontransported turkeys.
      These results suggest that transporting turkeys immediately before processing
      does not induce PSE meat and may actually improve water-holding properties.

PMID- 10947194
TI  - Effect of stunning current frequency on carcass downgrading and meat quality of
      turkey.
AB  - The objective of this study was to determine the effect of frequency of a 150 mA
      water-bath stunning current on turkey hen carcass and meat qualities. Fifty
      turkey hens were subjected to water-bath stunning with alternating current of
      various frequencies: 50 Hz (n = 12), 300 Hz (n = 14), 480 Hz (n = 12), and 600 Hz
      (n = 12); the duration of stunning was 4 s for each bird. Carcass defects such as
      engorged wing veins, red wing tips, and hemorrhages were recorded. Turkey meat
      quality traits (M. Pectoralis major) were assessed based on rigor mortis
      development, color, drip loss, cooking loss, tenderness, and cooking yield of
      cured products. The data showed that frequencies of 480 Hz and 600 Hz are
      associated with an increased rate of postmortem pH decline (during bleeding).
      This effect is most likely due to the occurrence of vigorous wing flapping during
      the first 3 min poststunning. Under the experimental conditions of the present
      work, the increase in rate of pH decline after stunning at 480 and 600 Hz did not
      induce carcass and meat quality defects. However, before any recommendation is
      given, the influence of stunning frequency on turkey meat quality needs to be
      evaluated under industrial conditions.

PMID- 10947195
TI  - Comparison of poultry processing equipment surfaces for susceptibility to
      bacterial attachment and biofilm formation.
AB  - During processing of poultry meat products, broiler carcasses come in contact
      with many solid surfaces. Bacteria from the carcasses can attach to wet equipment
      surfaces, form biofilms, and provide a source of cross-contamination for
      subsequent carcasses. In this study an array of common equipment surface
      materials was compared for susceptibility to bacterial attachment and biofilms.
      To model mixed microbial populations relevant to poultry processing, samples were
      taken directly from the processing line and exposed to the surface materials.
      Whole carcasses were rinsed with phosphate-buffered saline (100 mL), and the
      rinse was diluted in nutrient broth. Absorbance values (412 nm) of the
      suspensions at varying dilutions containing test surfaces were compared hourly
      with controls without test surfaces. The kinetics of bacterial attachment and
      biofilm formation on test surfaces were determined under the influence of pH,
      time, and bacterial cell density, and the elemental composition of the surface
      materials was determined by energy-dispersive X-ray analysis. Our results showed
      that surfaces vary in affinity for bacterial attachment and biofilm formation.
      Analysis by spectrophotometry and scanning electron microscopy confirmed that
      attachment to stainless steel, polyethylene, and belting was not significantly
      different from controls. Attachment to picker-finger rubber was significantly
      less than attachment to stainless steel and the other surfaces. In fact, picker
      finger rubber inhibits bacterial contamination. An increased understanding of
      bacterial attachment and biofilm formation will assist in the development of
      interventions to counteract these processes and, thereby, enhance plant
      sanitation and pathogen control.

PMID- 10947196
TI  - Feather release force in minimally scalded broilers stunned with carbon dioxide
      or electricity.
AB  - Broilers were stunned with carbon dioxide or electricity prior to slaughter to
      evaluate feather release force (FRF) following scalding with conventional or
      abbreviated scald methods. Broilers (n = 72) were stunned using an electrical
      saline stunner (35 mA, 60 Hz AC, 7 s) or shackle-line CO2 gas stunning tunnel (15
      to 40% CO2 gradient for 90 s). After bleeding for 90 s, the broilers were then
      scalded with a soft scald (53 C for 120 s) or a softer scald (53 C for 90 s).
      Within 2 min after scalding, feathers from the right femoral feather tract were
      removed perpendicularly using a force gauge to evaluate FRF. The FRF for the soft
      scald was higher than that for the softer scald. The FRF results indicated that
      there were no significant differences between the two stunning treatments (CO2
      and electrical) for either scalding treatment.

PMID- 10947198
TI  - Proceedings of the 4th International Workshop of the Adrenoleukodystrophy
      International Research Group (ALD-IRG), University of York, 3 September 1998.

PMID- 10947197
TI  - Defective folding and rapid degradation of mutant proteins is a common disease
      mechanism in genetic disorders.
AB  - Many disease-causing point mutations do not seriously compromise synthesis of the
      affected polypeptide but rather exert their effects by impairing subsequent
      protein folding or stability of the folded protein. This often results in rapid
      degradation of the affected protein. The concepts of such 'conformational
      disease' are illustrated by reference to cystic fibrosis, phenylketonuria and
      short-chain acyl-CoA dehydrogenase deficiency. Other cellular components such as
      chaperones and proteases, as well as environmental factors, may combine to
      modulate the phenotype of such disorders and this may open up new therapeutic
      approaches.

PMID- 10947199
TI  - Bone marrow transplantation for the treatment of X-linked adrenoleukodystrophy.
AB  - The effects of bone marrow transplantation (BMT) in X-linked childhood
      adrenoleukodystrophy (ALD) are described in four Japanese patients. Two older
      patients, 10-year-old boys with IQ 60 and difficulty in school, had favourable
      results. IQ levels and MRI findings were generally maintained after BMT. One
      patient showed improvement of gait disturbance. They have both attended ordinary
      schools after BMT, although a learning disorder persists. On the other hand, two
      other younger patients with a rapid course and indeterminate IQ at BMT showed
      deterioration of neurological functions. Indication for BMT seems to be a
      maintained IQ level, preferably higher than 80, since it seems to be difficult to
      normalize IQ level after BMT. Younger patients have higher risk of developing a
      rapidly progressive form of the disease. Identification of presymptomatic boys,
      and serial and careful follow-up by neuropsychological and neuroradiological
      studies, are essential prerequisites to successful BMT in X-ALD.

PMID- 10947200
TI  - Short-term effect of captopril on microalbuminuria in children with glycogen
      storage disease type Ia.
AB  - Early signs of renal dysfunction in glycogen storage disease type Ia (GSD Ia) are
      glomerular hyperfiltration and proteinuria. In a non-randomized study, the effect
      of captopril on the improvement of proteinuria in GSD Ia patients with
      microalbuminuria was investigated. A positive effect has been shown for the
      insulin-dependent diabetes mellitus patients. Microalbuminuria was defined as
      albumin/creatinine ratio (mg/mmol) more than 2.5 in spot urine. Nineteen (52.7%)
      out of 36 patients had microalbuminuria, and 8 patients received captopril at a
      dose of 1 mg/kg per day. Microalbuminuria was evaluated periodically during the
      follow-up period. Of the captopril-treated patients, one was lost to follow-up.
      In the remaining 7 patients, urinary albumin excretion normalized in 3 patients
      (42.9%) and decreased at least by 50% in another 3 patients (42.8%) after 6
      months of treatment. One patient, who was the oldest, did not have any benefit.
      In untreated patients, only two patients had a decrease in microalbuminuria of
      more than 50%. Patients with microalbuminuria had significantly higher blood
      lactate (p < 0.05) and plasma triglyceride (p < 0.01) concentrations and
      significantly lower blood bicarbonate concentration (p < 0.05) than those
      patients without it. Additionally, the patients with microalbuminuria had been
      diagnosed earlier than those without microalbuminuria (p < 0.05). Patients with
      microalbuminuria have more severe clinical and laboratory findings than those
      without microalbuminuria. Captopril at a dose of 1 mg/kg per day seems to be
      effective in at least 50% of GSD Ia patients with microalbuminuria.

PMID- 10947202
TI  - A rapid screening procedure for the diagnosis of peroxisomal disorders:
      quantification of very long-chain fatty acids, as dimethylaminoethyl esters, in
      plasma and blood spots, by electrospray tandem mass spectrometry.
AB  - A rapid method with potential to screen for many of the peroxisomal disorders
      using 5 microl of plasma or a 3-mm blood spot (3.6 microl blood impregnated on
      filter paper) is described. Fatty acids are liberated from plasma or blood spots
      and converted to dimethylaminoethyl esters. Trideuterated fatty acids, added as
      internal standards, are used to quantify eicosanoic (C20:0), docosanoic (C22:0),
      tetracosanoic (C24:0) and hexacosanoic (C26:0) acids by electrospray tandem mass
      spectrometry. The C26:0/C22:0 and C24:0/C22:0 ratios are significantly greater in
      the plasma of patients with peroxisomal disorders compared to controls. The
      C20:0/C22:0 ratio is elevated in the plasma of peroxisomal patients who
      accumulate phytanic acid. Blood spots collected from four peroxisomal patients
      between 2 and 10 days after birth and stored for up to 17 years, were shown to
      give between 33% and 233% higher C26:0/C22:0 ratios compared to age-matched
      controls.

PMID- 10947201
TI  - Regulation of cholesterol biosynthetic pathway in patients with the Smith-Lemli
      Opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is a recessively inherited birth disorder
      caused by a defect in 7-dehydrocholesterol (3beta-hydroxysteroid) delta7
      reductase, the final enzyme in cholesterol biosynthesis. To investigate in vivo
      regulation of the cholesterol biosynthetic pathway in SLOS, we measured hepatic
      microsomal sterol concentrations and activities of several key enzymes in the
      pathway, including HMG-CoA synthase, HMG-CoA reductase, squalene synthase and 7
      dehydrocholesterol delta7-reductase in liver specimens from a patient with SLOS
      and 11 controls. Hepatic microsomal 7-dehydrocholesterol delta7-reductase
      activity in the patient was less than 1% of the control mean, and decreased
      cholesterol concentration and markedly increased 7- and 8-dehydrocholesterol
      concentrations were observed in the patient's microsomes. HMG-CoA synthase and
      squalene synthase activities in the patient were upregulated to 149% and 532%,
      respectively, while the activity of HMG-CoA reductase, the rate-limiting enzyme
      in the pathway, was reduced to 39% of the control mean. Downregulation of HMG-CoA
      reductase activity in SLOS was supported by measuring plasma levels of mevalonic
      acid, the immediate product of HMG-CoA reductase. The levels in SLOS patients (n
      = 9) were significantly low compared with age-matched controls (n = 8) (12+/-2 vs
      28 + 6nmol/L, p < 0.05). These results suggest that in most SLOS patients in vivo
      HMG-CoA reductase is not stimulated in spite of blocked cholesterol biosynthetic
      pathway and reduced plasma and hepatic cholesterol concentrations.

PMID- 10947203
TI  - Behavioural and emotional problems in early-treated adolescents with
      phenylketonuria in comparison with diabetic patients and healthy controls.
AB  - Even early-treated patients with phenylketonuria (PKU) have a higher risk of
      psychosocial maladjustment. This study was performed to determine whether
      emotional and behavioural problems are specific in phenylketonurics and whether
      they depend on the quality of biochemical control. This comparative study covered
      42 PKU patients aged 10-18 years (mean 14.7 years) and 42 diabetic patients
      matched for sex, age and socioeconomic status. Patients' groups were compared
      with a control sample of healthy controls (n = 2900) from an epidemiological
      study. We used the Child Behavior Check List (CBCL) according to Achenbach,
      intelligence quotient (IQ) test according to Weiss, and monitoring of blood
      phenylalanine concentrations and HBA1 concentrations. Internalizing problems such
      as depressive mood, anxiety, physical complaints or social isolation were
      significantly elevated in both phenylketonuric and diabetic patients, whereas
      externalizing problems were not. The two patient groups did not differ
      significantly either in the degree or in the pattern of their psychological
      profile. In both groups no significant correlations could be computed between the
      psychological characteristics and the biochemical control, the IQ, and the
      socioeconomic status. No patient was undergoing psychiatric treatment or
      psychotherapy. Our results strongly support a psychological perspective for the
      development of behavioural and emotional problems in both phenylketonuric and
      diabetic patients. Thus, medical treatment should be accompanied by psychological
      support for the families.

PMID- 10947204
TI  - Molecular characterization of methylmalonate semialdehyde dehydrogenase
      deficiency.
AB  - Three patients have been reported with (putative) methylmalonic semialdehyde
      dehydrogenase (MMSDH) deficiency. The urine metabolic pattern was strikingly
      different in all, including beta-alanine, 3-hydroxypropionic acid, both isomers
      of 3-amino- and 3-hydroxyisobutyric acids in one and 3-hydroxyisobutyric and
      lactic acids in a second, and mild methylmalonic aciduria in a third patient. In
      an effort to clarify these disparate metabolite patterns, we completed the cDNA
      structure, and characterized the genomic structure of human MMSDH gene in order
      to undertake molecular analysis. Only the first patient had alterations in the
      MMSDH coding region, revealing homozygosity for a 1336G > A transversion, which
      leads to substitution of arginine for highly conserved glycine at amino acid 446.
      No abnormalities of the MMSDH cDNA were detected in the other patients. These
      data provide the first molecular characterization of an inborn error of
      metabolism specific to the L-valine catabolic pathway.

PMID- 10947206
TI  - Very high plasma leucine concentrations without neurological symptoms in a
      patient with classical maple syrup urine disease.

PMID- 10947205
TI  - Reduction of large neutral amino acid concentrations in plasma and CSF of
      patients with maple syrup urine disease during crises.
AB  - Neurological dysfunction is common in patients with maple syrup urine disease
      (MSUD). However, the mechanisms underlying the neuropathology of this disorder
      are poorly understood. We determined the concentrations of all amino acids in
      plasma of patients with MSUD during crises (with severe CNS symptoms) and after
      recovery in the hope of detecting possible alterations of these levels during
      metabolic decompensation. Blood samples obtained from 11 children with MSUD aged
      1 month to 7 years and from 10 age-matched controls (5 months to 6 years) with no
      evidence of metabolic disease were examined for their amino acid content by high
      performance liquid chromatography. We observed that leucine, isoleucine and
      valine concentrations were respectively 30, 9 and 3 times higher than normal
      values, whereas the concentrations of the large neutral amino acids (LNAA)
      phenylalanine, tyrosine, tryptophan and methionine were significantly lower
      during metabolic decompensation as compared to the controls. In addition,
      concentrations of leucine, but not of valine or isoleucine, were inversely
      related to the LNAA concentrations in plasma. The concentrations of these amino
      acids in plasma returned to normal values when patients were clinically well. CSF
      amino acid concentrations also showed decreased amounts of LNAA and increased
      concentrations of branched-chain amino acids. It is possible that the decrease in
      plasma concentrations of LNAA may lead to a deficit of these essential amino
      acids in the brain as well as of their products such as proteins and
      neurotransmitters, a fact that might be related to the neurological dysfunction
      of MSUD.

PMID- 10947207
TI  - I-cell disease complicated by unusual dilatative cardiomyopathy.

PMID- 10947208
TI  - Arginase deficiency presenting with cerebral oedema and failure to thrive.

PMID- 10947209
TI  - The HELLP syndrome associated wiht fetal medium-chain acyl-CoA dehydrogenase
      deficiency.

PMID- 10947210
TI  - Three siblings with nonketotic hyperglycinaemia, mildly elevated plasma
      homocysteine concentrations and moderate methylmalonic aciduria.

PMID- 10947211
TI  - Molecular basis of mild hyperphenylalaninaemia in Turkey.

PMID- 10947212
TI  - Methylenetetrahydrofolate reductase 677C > T mutation and epilepsy.

PMID- 10947213
TI  - Identification of a 5' splice junction mutation in the debranching enzyme gene in
      a Japanese patient with glycogen storage disease type IIIa.

PMID- 10947214
TI  - Glycopeptide resistance in coagulase-negative staphylococci.
AB  - Coagulase-negative staphylococci (CNS) were the first organisms in which acquired
      glycopeptide resistance was recognized. Ever since the early reports, it has been
      apparent that resistance to teicoplanin is more common than that to vancomycin
      and that resistance occurs mostly in species such as Staphylococcus haemolyticus
      and Staphylococcus epidermidis. The minimum inhibitory concentrations (MICs) of
      teicoplanin for CNS usually fall over a wide range, and, especially in some
      methicillin-resistant isolates of the two above-mentioned species, they can reach
      and even exceed the resistance breakpoint, whereas vancomycin MICs tend to remain
      more stable over a narrower range within the limits of susceptibility. CNS
      strains intermediately susceptible and even resistant not only to teicoplanin but
      also to vancomycin have, however, been isolated, most frequently from patients
      subjected to prolonged glycopeptide treatment. Laboratory detection of
      glycopeptide-resistant CNS may be problematic, mainly because susceptibility
      tests, particularly those for teicoplanin, are influenced by various technical
      factors, and agar diffusion tests may yield false susceptibility data. In studies
      with experimental glycopeptides, some molecules have exhibited improved in vitro
      activity compared with teicoplanin and vancomycin, but these encouraging
      microbiological findings have not usually been followed by in vivo trials.
      Stepwise and single-step exposure to teicoplanin and vancomycin has allowed
      stable clones for which glycopeptide MICs are increased to be obtained from
      susceptible CNS strains, particularly strains of Staphylococcus haemolyticus and
      Staphylococcus epidermidis. In these studies, resistance to teicoplanin was
      generally easier to obtain than resistance to vancomycin, and the levels of
      teicoplanin resistance were higher. Population studies have demonstrated the
      usually heterogeneous nature of glycopeptide resistance in CNS. Although
      glycopeptide-resistant CNS have been shown to differ in several features from
      their glycopeptide-susceptible counterparts, the exact mechanism of
      staphylococcal glycopeptide resistance remains unknown.

PMID- 10947215
TI  - Validation of a diagnosis model for differentiating bacterial from viral
      meningitis in infants and children under 3.5 years of age.
AB  - The aim of this study was to validate, in a population of infants and children
      under 3.5 years of age, a diagnosis model that provides a figure for the
      probability of bacterial meningitis (pABM), based on four parameters collected at
      the time of the first lumbar tap: the cerebrospinal fluid (CSF) protein level,
      CSF polymorphonuclear cell count, blood glucose level, and leucocyte count. The
      best cut-off value for distinguishing between bacterial and viral meningitis was
      previously found to be 0.1, since 99% of meningitides associated with pABM<0.1
      were viral. The charts of 103 consecutive children aged 0.1-3.5 years who had
      been hospitalised for acute meningitis were reviewed. Each case was sorted into
      the following three categories for aetiology: bacterial (positive CSF culture,
      n=48); viral (negative CSF culture and no other aetiology, and no antibiotic
      treatment after diagnosis, n=36); and undetermined (fitting neither of the first
      two definitions, n=19). After computation of pABM values in each case, the
      predictive values of the model were calculated for different pABM cut-off values.
      The results confirmed that the best cut-off pABM value was 0.1, for which the
      positive and negative predictive values in this model were 96% and 97%,
      respectively. Only one case of bacterial meningitis (lumbar tap performed early
      in an infant with meningococcal purpura fulminans with negative CSF culture) was
      associated with a pABM value of <0.1. This model is quite reliable for
      differentiating between bacterial and viral meningitis in children under 3.5
      years of age, and it may enable physicians to withhold antibiotics in cases of
      meningitis of uncertain aetiology.

PMID- 10947216
TI  - Prospective validation of a diagnosis model as an aid to therapeutic decision
      making in acute meningitis.
AB  - The aim of this study was to validate a diagnosis model that provides pABM, the
      probability of bacterial versus viral meningitis, based on four parameters
      collected at the time of first lumbar tap: cerebrospinal fluid protein level,
      cerebrospinal fluid polymorphonuclear cell count, blood glucose level, and
      leucocyte count. The model was evaluated prospectively as an aid to therapeutic
      decision-making in 109 consecutive patients with acute meningitis and negative
      cerebrospinal fluid Gram stain. In each case pABM was computed before a
      therapeutic decision and three diagnoses were established successively: (i)
      clinical evaluation, i.e. before pABM computation (bacterial meningitis, viral
      meningitis, or meningitis of undetermined origin); (ii) computation of pABM
      (viral meningitis if pABM< 0.1, bacterial meningitis otherwise); and (iii)
      determination of definitive diagnosis (bacterial meningitis: positive
      cerebrospinal fluid culture; viral meningitis: negative cerebrospinal fluid
      culture, no other aetiology and no treatment; meningitis of undetermined origin:
      cases fitting neither of the first two diagnoses). The computed diagnosis was
      viral meningitis in 78 of the 80 cases diagnosed definitively as viral
      meningitis, and bacterial meningitis in four of the five cases diagnosed
      definitively as bacterial meningitis. Negative and positive predictive values and
      accuracy of the model were 98.7%, 66.7%, and 96.5%, respectively. The clinical
      diagnosis was undetermined in 22 cases, 15 of which were diagnosed definitively
      as viral cases; in all of these 15 cases, the computed diagnosis was viral
      meningitis, leading the physician to refrain from starting antibiotics in all of
      them. The results confirm that the model evaluated is reliable and aids in the
      identification of patients in whom antibiotics can be safely avoided.

PMID- 10947217
TI  - Swiss Army Survey in Switzerland to determine the prevalence of Francisella
      tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia
      burgdorferi sensu lato, and tick-borne encephalitis virus in ticks.
AB  - A total of 6071 Ixodes ricinus ticks were collected on Swiss Army training
      grounds in five regions of Switzerland. The aim of the survey was to assess the
      prevalence of ticks infected with the human pathogens Francisella tularensis,
      members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu
      lato, and the European tick-borne encephalitis virus. TaqMan PCR (PE Biosystems,
      USA) and TaqMan RT-PCR (PE Biosystems) analyses were performed on DNA and RNA
      extracted from pools of ten ticks grouped by gender. Here, for the first time, it
      is shown that ticks may harbor Francisella tularensis in Switzerland, at a rate
      of 0.12%. Furthermore, 26.54% of the ticks investigated harbored Borrelia
      burgdorferi sensu lato, 1.18% harbored members of the Ehrlichia phagocytophila
      genogroup, and 0.32% harbored the European tick-borne encephalitis virus. A new
      instrumentation was applied in this study to carry out and analyze more than 2300
      PCR reactions in only 5 days. Furthermore, the results reveal that people working
      in outdoor areas, including army personnel on certain training grounds
      contaminated with ticks containing tick-borne pathogens, are at risk for
      different tick-borne diseases.

PMID- 10947218
TI  - Diphtheria antibody levels in the Italian Population.
AB  - Immunity to diphtheria was assessed in serum samples obtained from 3111 healthy
      Italian males and females aged 0-84 years. Diphtheria antitoxin was tested using
      a double-antigen, time-resolved fluorescence immunoassay (DA-DELFIA). According
      to internationally accepted criteria, antitoxin concentrations < 0.01 IU/ml
      indicate susceptibility to diphtheria, those > or = 0.01-0.09 IU/ml provide basic
      or inadequate protection, and concentrations > or =0.1 IU/ml are protective. By
      these criteria, 9.9% (95% CI 8.9 to 11.18) of the participants were susceptible
      to diphtheria, 30.2% (95% CI, 28.6 to 31.9) had basic protection, and 59.9% (95%
      CI, 58.1 to 61.6) were protected. The prevalence of unprotected individuals
      showed an age-related increase, up to the 45-49-year-old age group for females
      and the 50-54-year-old age group for males (34.9% and 31.3% of individuals,
      respectively). The prevalence of immunity did not significantly differ in
      relation to sex in any of the age groups. These results indicate that booster
      shots should be routinely provided to the adult population in order to maintain a
      protective level of diphtheria antibodies.

PMID- 10947219
TI  - Evaluation of immunological rapid urease testing for detection of Helicobacter
      pylori.
AB  - The aim of this study was to evaluate in clinical specimens the immunological
      rapid urease test (IRUT), a new diagnostic system for detection of Helicobacter
      pylori which employs a monoclonal antibody against Helicobacter pylori urease.
      Helicobacter pylori urease adsorbed on a solid-phase tip coated with a monoclonal
      antibody against Helicobacter pylori urease after 15 min of incubation with a
      gastric mucus sample solution was measured by the pH change of the urea solution
      inside the tip. The detection limit of Helicobacter pylori urease using this
      system was determined and compared with that of a commercially available rapid
      urease test. Clinical evaluation of the system was performed in 155 patients. The
      IRUT could detect 0.25 milli-international units (mIU) of Helicobacter pylori
      urease per milliliter in less than 20 min. If a patient with at least one
      positive result in a standard test for Helicobacter pylori was considered to be
      Helicobacter pylori positive, the sensitivity, specificity, positive and negative
      predictive values of the system were calculated as 95.2%, 98.9%, 98.4% and 96.8%,
      respectively. However, 10 of 19 Helicobacter pylori-positive patients in whom the
      pH change was less than 0.1 had negative results in at least one of the standard
      tests, whereas the IRUT correctly detected Helicobacter pylori in all but 3 of
      these 19 patients. The IRUT accurately determined the Helicobacter pylori status
      of 75 (98.7%) of 76 patients who had completed treatment. This system has high
      sensitivity for the detection of Helicobacter pylori, especially in patients with
      low urease activity.

PMID- 10947220
TI  - Novel genus-specific PCR-based assays for rapid identification of Neisseria
      species and Neisseria meningitidis.
AB  - This study presents the development of polymerase chain reaction (PCR)-based
      tests for the identification and detection of Neisseria species and Neisseria
      meningitidis. Currently, isolating and identifying these pathogens using
      conventional biochemical methods require 48-72 h. To improve speed and accuracy
      in diagnosing Neisseria infections, simple PCR-based tests that are specific for
      the genus Neisseria and the species Neisseria meningitidis have been developed.
      The genus-specific and species-specific DNA sequences were chosen by selecting
      and analyzing available database sequences. Neisseria-specific and Neisseria
      meningitidis-specific primer pairs were derived from the genes asd (coding for
      the aspartate beta-semialdehyde dehydrogenase) and ctrA (coding for a conserved
      outer membrane protein), respectively. Both the Neisseria-specific and Neisseria
      meningitidis-specific PCR assays were specific (they amplified only DNA from the
      target genus or species, out of 84 bacterial species tested). In addition, the
      Neisseria-specific assay amplified DNA from 321 of 322 strains tested
      representing 13 species of Neisseria, while the Neisseria meningitidis-specific
      assay amplified DNA from all 256 strains tested representing nine serogroups of
      Neisseria meningitidis. These PCR assays, which can be combined in multiplex,
      have been adapted to ensure that they are simple and can be performed within
      approximately 90 min. The tests provide new diagnostic tools for identifying
      Neisseria infections.

PMID- 10947221
TI  - Genetic and antigenic characteristics of Neisseria meningitidis strains isolated
      in the Czech Republic in 1997-1998.
AB  - Strains of Neisseria meningitidis isolated from patients and asymptomatic
      individuals who had been in contact with patients were investigated using four
      typing methods with the aim of identifying any heterogeneity and/or homogeneity
      among the strains. In 1993, a dramatic change in the incidence and severity of
      invasive meningococcal disease in the Czech Republic occurred as a consequence of
      the appearance of a Neisseria meningitidis strain of phenotype C:2a:P1.5,2 and
      electrophoretic type ET-15, belonging to the ET-37 complex, which had not
      previously been identified in this country. Presented here are the results of a
      study of the relationships between 58 Neisseria meningitidis isolates collected
      between January 1997 and June 1998. Forty-nine isolates originating from patients
      with invasive meningococcal disease and nine from healthy contacts were analyzed
      using the following four methods: whole-cell enzyme immunoassay, multilocus
      enzyme electrophoresis, pulsed-field gel electrophoresis, and randomly amplified
      polymorphic DNA analysis. A high prevalence of phenotype C:2a:P1.5,2
      electrophoretic type ET-15 was confirmed among the patients' strains.
      Nevertheless, during the study period, they became heterogeneous. Strains
      isolated from healthy contacts showed greater heterogeneity in serological
      phenotypes and electrophoretic types from the beginning of the study, and
      electrophoretic type ET-15 strains were less frequent. Within the electrophoretic
      type ET-15 clone, strains showing the identical serological phenotype (with the
      exception of one isolate) were indistinguishable using randomly amplified
      polymorphic DNA analysis, while pulsed-field gel electrophoresis revealed
      heterogeneity with 12 pulsed-field gel electrophoretic types identified. The
      strains from the same cluster displaying the same serological phenotype were
      indistinguishable with any of the methods used.

PMID- 10947222
TI  - Analysis of risk factors for ventilator-associated pneumonia in a
      multidisciplinary intensive care unit.
AB  - A prospective study was conducted to determine the incidence, risk factors and
      pathogens of ventilator-associated pneumonia (VAP) in 198 patients requiring
      mechanical ventilation for more than 48 hours. VAP occurred in 67 (33.8%)
      patients. Risk factors associated with VAP were admission APACHE II score >20
      (odds ratio [OR] 4.77, 95% confidence interval [CI] 2.04-11.27, P<0.001),
      mechanical ventilation > 10 days (OR 44.4, 95% CI 2.16-26.7, P< 0.0001), ICU
      length of stay >10 days (OR 9.4, 95% CI 3.55-25.65, P< 0.0001), and admission
      PaO2/FiO2 ratio <200mmHg (OR 3.4, 95% CI 1.00-11.41, P<0.05). Logistic regression
      analysis showed a relationship between VAP and length of stay in ICU, duration of
      fever and presence of catheter-related infection. The pathogens isolated were
      predominantly gram-negative bacteria (83.2%), with a high proportion of
      Acinetobacter spp. (35%) resistant to commonly used antimicrobial agents. The
      mortality rate was not influenced by VAP.

PMID- 10947223
TI  - Outbreak of typhoid fever on the French Riviera.
AB  - A case-control study was conducted to establish the source of a community
      outbreak of typhoid fever in Utelle, France, a village located in the Alpes
      Maritimes district of the French Riviera. Thirteen confirmed cases of typhoid
      fever and 41 confirmed community controls were included in the study. Cases and
      controls did not differ regarding ingestion of water. Multivariate logistic
      regression analysis identified consumption of pork meats during a village
      festival as the only statistically significant risk factor for typhoid fever
      after adjusting for age and sex (odds ratio, 76.0; 95% confidence interval, 3.5
      1660). Assessment of food-handling procedures at the inn where the food had been
      prepared showed that the refrigeration and cooking facilities were inadequate to
      maintain a proper sanitary environment during the preparation of a meal for 350
      people. Although the exact cause of the epidemic could not be confirmed, food
      contaminated by a chronic typhi carrier is the most plausible hypothesis.

PMID- 10947224
TI  - Fungemia with Saccharomyces cerevisiae in two newborns, only one of whom had been
      treated with ultra-levura.
AB  - Ultra-Levura (Upsamedica, Spain) is a yeast (Saccharomyces boulardii) widely used
      as a biotherapeutic agent. To date, few adverse effects have been reported,
      although fungemia with Saccharomyces cerevisiae can occur in weak and
      immunosuppressed patients. Reported here are two cases of fungemia with
      Saccharomyces cerevisiae. One patient had been treated with Ultra-Levura and the
      other contracted the infection from the first. This is the first report of
      infection with Saccharomyces boulardii (Saccharomyces cerevisiae) in a patient
      who was not being treated with the agent.

PMID- 10947225
TI  - Pulmonary involvement in leptospirosis.
AB  - The objective of this study was to assess the incidence of pulmonary involvement
      in a cohort of 26 patients in whom a diagnosis of leptospirosis had been made.
      Seventeen of the 26 patients had respiratory symptoms. Of these 17 patients, 13
      had radiographs showing pulmonary abnormality. The most frequent finding was a
      bilateral patchy alveolar-acinar pattern in six patients. Three patients
      developed acute respiratory distress syndrome and died due to multiorgan failure.
      Only cigarette smoking was significantly associated with respiratory involvement
      (odds ratio, 19.2; 95% CI, 1.7-250; P < 0.001). The results indicate that
      pulmonary manifestations are observed in a high percentage of patients with
      leptospirosis. Cigarette smoking is a risk factor for the development of
      pulmonary involvement in human leptospirosis.

PMID- 10947226
TI  - Neisseria meningitidis serogroup W-135 primary monarthritis of the hip in an
      immunocompetent child.
AB  - Reported here is the first known case of primary monoarthritis of the hip due to
      Neisseria meningitidis W-135. The isolate was obtained from an immunocompetent
      child suffering from acute hip pain as the only symptom upon presentation at the
      hospital. Meningococcal infection must be considered in the diagnosis of any
      child presenting with arthritis, even if afebrile and without rash.

PMID- 10947227
TI  - Use of the ligase detection reaction-polymerase chain reaction to identify point
      mutations in extended-spectrum beta-lactamases.
AB  - The aim of this study was to detect point mutations in extended-spectrum beta
      lactamase (ESBL) genes in a background of wild-type (non-ESBL-producing) bacteria
      using a highly sensitive and specific method developed for this purpose. The
      ligase detection reaction-polymerase chain reaction (LDR-PCR) method was used to
      test different ESBL-producing strains and clinical isolates for a specific point
      mutation in the bla SHV-ESBL gene (glycine to serine mutation at position 238)
      and was compared with the commercially available E test ESBL (AB Biodisk,
      Sweden). Nine of the 40 clinical isolates tested were positive for the bla SHV
      ESBL point mutation when tested by the LDR-PCR method but negative when tested by
      the E test. In contrast to the E test or other molecular genetic tests, the LDR
      PCR method is able to identify a single bacterium with a point mutation in a
      background of 100,000 wild-type (non-ESBL-producing) bacteria.

PMID- 10947228
TI  - Usefulness of simultaneous detection of toxin A and glutamate dehydrogenase for
      the diagnosis of Clostridium difficile-associated diseases.
AB  - The aim of this study was to evaluate an immunoassay (Triage; Biosite
      Diagnostics, BMD, France) for detecting both a specific antigen of Clostridium
      difficile (glutamate dehydrogenase [GDH]) and toxin A. Evaluation of the test was
      carried out in 304 fecal samples from patients suspected of having Clostridium
      difficile-associated diseases. The results with GDH and toxin A were compared
      with those of a culture and cytotoxicity assay (toxin B). The prevalence rates
      for toxin B-positive and culture-positive fecal samples were 11.2% and 25%,
      respectively. The sensitivity of the Triage immunoassay was 90.8% for GDH and
      79.4% for toxin A. A negative result with both toxin A and GDH was very reliably
      able to eliminate a diagnosis of Clostridium difficile-associated disease
      (negative predictive value 99.6%). Triage is a very rapid (20 min) and easy-to
      perform test. It could be useful for diagnostic purposes and also for detecting
      nontoxigenic strains in epidemiogical studies.

PMID- 10947229
TI  - Evaluation of four enzyme immunoassays for the detection of Giardia lamblia
      antigen in stool specimens.
AB  - Four enzyme immunoassays for the detection of Giardia lamblia antigen in stool
      specimens were evaluated: the ProSpecT Giardia Microplate Assay (Alexon, USA),
      the Giardia CELISA (Cellabs, Australia), the DSL-Giardia-ELISA (DSL. Germany),
      and the Melotest Giardiasis Ag (Melotec, Spain). Microscopic examination and
      enzyme immunoassays were performed on 168 stool specimens collected from 168
      patients suspected to have giardiasis. All assays were easy to perform. The
      ProSpecT Giardia assay had the highest sensitivity of the assays evaluated (91%),
      and its interpretation was the easiest. The sensitivity of the three other assays
      ranged from 63 to 81%. The ProSpecT Giardia assay can be useful to detect Giardia
      lamblia and may replace microscopic examination in areas of high endemicity.

PMID- 10947230
TI  - Pneumococcal bacteraemia and problems associated with preliminary identification
      and interpretation of positive blood culture smears.

PMID- 10947231
TI  - Nontoxigenic vibrio Cholerae O1 bacteremia: case report and review.

PMID- 10947232
TI  - Excitatory and inhibitory receptive fields of tectal cells are differentially
      modified by magnocellular and parvocellular divisions of the pigeon nucleus
      isthmi.
AB  - It has been known that magnocellular and parvocellular divisions of the pigeon
      nucleus isthmi exert excitatory and inhibitory actions on tectal cells,
      respectively. The present study shows that injection of N-methyl-D-aspartate into
      the parvocellular division results in an increase in responsive strength and
      extent of the inhibitory receptive fields, which expand into the excitatory
      receptive fields of tectal cells. This injection concurrently leads to a decrease
      in responsiveness and extent of the excitatory fields. On the other hand,
      injection of acetylcholine into the magnocellular division enhances visual
      responsiveness, although the excitatory field is not obviously changed in extent.
      Meanwhile, strength and extent of the inhibitory fields are decreased by
      acetylcholine. The excitatory and inhibitory fields are reduced in both strength
      and extent by magnocellular and parvocellular injection of lidocaine,
      respectively. It suggests that isthmic inputs from both parvocellular and
      magnocellular divisions converge onto the same tectal cells, and the
      magnocellular and parvocellular subnuclei can modulate excitatory and inhibitory
      receptive fields of tectal cells, respectively, with some interactions between
      both fields.

PMID- 10947233
TI  - Antennal response of codling moth males, Cydia pomonella L. (Lepidoptera:
      Tortricidae), to the geometric isomers of codlemone and codlemone acetate.
AB  - Single sensillum recordings from Cydia pomonella male antennae showed three
      different types of receptor neurons. The most abundant type was most sensitive to
      the main pheromone compound (E,E)-8,10-dodecadienol, while its response to the
      geometric isomers E,Z, Z,E and Z,Z was comparable to a tenfold lower dose of
      (E,E)-8,10-dodecadienol. This neuron type also responded to the four behaviorally
      antagonistic isomers of (delta,delta)-8,10-dodecadienyl acetate, among which it
      was most sensitive to the E,E isomer. Cross-adaptation studies showed that these
      compounds were all detected by the same receptor neuron type. Receptor neurons
      specifically tuned to (E,Z) or (Z,Z)-8,10-dodecadienol were not found, although
      these two compounds are behaviorally active. A second type of receptor neuron
      responded to all isomers of (delta,delta)-8,10-dodecadienyl acetate and was most
      sensitive to the E,E isomer. This neuron type did not respond to any of the
      isomers of (delta,delta)-8,10-dodecadienol. A third receptor neuron type was
      highly sensitive to the plant compound alpha-farnesene. The finding that the
      receptor neuron type tuned to the main pheromone compound responded even to
      strong behavioral antagonists aids the interpretation of ongoing behavioral
      studies for the development of the mating disruption technique in codling moth.

PMID- 10947234
TI  - Pattern vision of the honeybee (Apis mellifera). What is an oriented edge?
AB  - Pairs of black patterns on a white background, one rewarded the other not, were
      presented vertically each in one arm of a Y-maze. During training the locations
      of the black areas were changed every 5 min to prevent the bees using them as
      cues, but cues from edges were kept consistent. Bees detect orientation even in a
      gradient that subtends 36 degrees from black to white (normal to the edge).
      Orientation cues in short lengths of edge are detected and summed on each side of
      the fixation point, irrespective of the lay-out of the pattern. Edges at right
      angles reduce the total orientation cue. The polarity of edges in a sawtooth
      grating is weakly discriminated, but not the orientation of a fault line where
      two gratings meet. Edge quality can be discriminated, but is not recognised in
      unfamiliar orientations. When spot location is excluded as a cue, the orientation
      of a row of spots or squares which individually provide no net orientation cue is
      not discriminated. In conclusion, when locations of black areas are shuffled, the
      bees remember the sum of local orientation cues but not the global pattern, and
      there is no re-assembly of a pattern based on differently oriented edges. A
      neuronal model consistent with these results is presented.

PMID- 10947235
TI  - Responses of olfactory receptor neurons in Utetheisa ornatrix to gender-specific
      odors.
AB  - We recorded the electrophysiological responses of individual olfactory receptor
      neurons in sensilla trichodea on the antennae of adult arctiid moths, Utetheisa
      ornatrix, to stimulation with volatiles associated with both sexes. All trichoid
      sensilla contain at least two receptor neurons, each with distinct action
      potential amplitudes and waveforms, that respond dichotomously to male and female
      odors. Although, neither female neuron responds to extracts of coremata or the
      male-produced pheromone hydroxydanaidal, they do respond in a gender-specific
      manner to the volatiles emanating from whole pupae, hemolymph, thoracic froth,
      and adult animals of several ages. Thoracic froth, which contains pyrrolizidine
      alkaloids, is thought to play a role in defense. Froth from moths reared on
      diets, with or without added pyrrolizidine alkaloids, were equally effective in
      eliciting gender-specific patterns of response. Male trichoid receptor neurons
      respond to these same materials with similar patterns of activation. These
      receptor neurons provide information about substances, which we have termed
      "gender odors," that are persistently emitted by nearby animals. These substances
      do not appear to be the same as those already known to be involved in defense or
      the sexual dialog between individuals.

PMID- 10947236
TI  - Responses of the infrared sensilla of Melanophila acuminata (Coleoptera:
      Buprestidae) to monochromatic infrared stimulation.
AB  - The pit organs of the beetle Melanophila acuminata were stimulated with
      monochromatic infrared radiation using a continuous wave CO overtone infrared
      laser. Best sensitivity was in the wavelength range 2.8-3.5 micron. In this range
      a stimulus intensity of 14.7 mW cm(-2) was sufficient to generate single action
      potentials. At a wavelength of 5 microm receptor performance significantly
      decreased. An increase in stimulus intensity caused a decrease in response
      latency and an increase in the number of action potentials elicited. At a given
      wavelength (3.4 microm) the dynamic amplitude range of action potential responses
      covered 12 dB. At high stimulus intensities (94.2 mW cm(-2)) a stimulus duration
      of 4 ms was sufficient to generate one to two action potentials and a stimulus
      duration of 60 ms already caused response saturation (with up to nine action
      potentials). In a repetitive stimulus regime distinct receptor potentials were
      visible up to a frequency of 600 Hz.

PMID- 10947237
TI  - Comparative thermoregulation of sympatric endothermic and ectothermic cicadas
      (Homoptera: Cicadidae: Tibicen winnemanna and Tibicen chloromerus).
AB  - Measurements of body temperature in the field demonstrated that endothermic
      cicadas regulate body temperature by behavioral mechanisms as well as by
      endogenous heat production. Regression analysis suggests both endothermic and
      ectothermic species are thermoregulating. Body temperature of endothermically
      active cicadas without access to exogenous heat is approximately the same as the
      body temperature of basking cicadas. Tibicen winnemanna (Davis) raises body
      temperature in the field with the heat produced in flight or through the
      activation of the flight musculature without the act of flight. T. chloromerus
      (Walker) uses solar radiation to elevate body temperature to the level necessary
      for activity. The thermal responses of each species are related to its activity
      patterns with minimum flight temperature and shade-seeking temperatures
      significantly lower in the endothermic T. winnemanna. Heat torpor temperature
      appears to be related to the environment rather than behavior pattern. Endothermy
      in cicadas may serve to uncouple reproductive behavior from environmental
      constraints; to circumvent possible thermoregulatory problems; to permit the
      utilization of habitats unavailable to strictly ectothermic cicadas; to reduce
      predation; to optimize broadcast coverage and sound transmission; and to decrease
      possible acoustic interference.

PMID- 10947238
TI  - Operant conditioning of antennal muscle activity in the honey bee (Apis mellifera
      L.).
AB  - Antennal movements of the honey bee can be conditioned operantly under laboratory
      conditions. Using this behavioural paradigm we have developed a preparation in
      which the activity of a single antennal muscle has been operantly conditioned.
      This muscle, the fast flagellum flexor muscle, is innervated by an identified
      motoneuron whose action potentials correlate 1:1 with the muscle potentials. The
      activity of the fast flagellum flexor muscle was recorded extracellularly from
      the scapus of the antenna. The animal was rewarded with a drop of sucrose
      solution whenever the muscle activity exceeded a defined reward threshold. The
      reward threshold was one standard deviation above the mean spontaneous frequency
      prior to conditioning. After ten conditioning trials, the frequency of the muscle
      potentials had increased significantly compared to the spontaneous frequency. The
      conditioned changes of frequency were observed for 30 min after conditioning. No
      significant changes of the frequency were found in the yoke control group. The
      firing pattern of the muscle potentials did not change significantly after
      conditioning or feeding. Fixing the antennal joints reduces or abolishes
      associative operant conditioning. The conditioned changes of the frequency of
      muscle potentials in the freely moving antenna are directly comparable to the
      behavioural changes during operant conditioning.

PMID- 10947239
TI  - Sex pheromone mimicry in the early spider orchid (ophrys sphegodes): patterns of
      hydrocarbons as the key mechanism for pollination by sexual deception.
AB  - We investigated the female-produced sex pheromone of the solitary bee Andrena
      nigroaenea and compared it with floral scent of the sexually deceptive orchid
      Ophrys sphegodes which is pollinated by Andrena nigroaenea males. We identified
      physiologically and behaviorally active compounds by gas chromatography with
      electroantennographic detection, gas chromatography-mass spectrometry, and
      behavioral tests in the field. Dummies scented with cuticle extracts of virgin
      females or of O. sphegodes labellum extracts elicited significantly more male
      reactions than odorless dummies. Therefore, copulation behavior eliciting
      semiochemicals are located on the surface of the females' cuticle and the surface
      of the flowers. Within bee and orchid samples, n-alkanes and n-alkenes,
      aldehydes, esters, all-trans-farnesol and all-trans-farnesyl hexanoate triggered
      electroantennographic responses in male antennae. Most of the alkanes and alkenes
      occurred in similar patterns both in the bees and orchids. O. sphegodes leaf
      extracts contained mostly the same compounds but in different proportions. In
      behavioral tests with synthetic compounds, blends of alkenes triggered
      significantly more approaches and pounces of the males whereas alkanes were not
      more attractive than odorless dummies. Since alkanes and alkenes together were
      most attractive, we conclude they constitute the bees' sex pheromone as well as
      the pseudocopulation-behavior releasing orchid-odor bouquet.

PMID- 10947240
TI  - Effects of exogenous serotonin on a motor behavior and shelter competition in
      juvenile lobsters (Homarus americanus).
AB  - Three experiments were conducted to determine (1) the pharmacodynamics of 5
      hydroxytryptamine in juvenile lobsters; (2) the effects of 5-hydroxytryptamine,
      using a range of dosages, on a motor behavior used to escape an aversive
      situation; and (3) the effect of doses that did and did not inhibit this motor
      behavior on measures of dominance and shelter competition. The fate of 5
      hydroxytryptamine in hemolymph over a 60-min post-injection period showed that
      the concentration fell rapidly to a low plateau that was maintained for at least
      1 h. Low doses of 5-hydroxytryptamine did not affect locomotor behavior, but
      higher doses inhibited it. Dominance and subsequent possession of a shelter were
      unaffected by a low dose of 5-hydroxytryptamine but a higher dose that inhibited
      locomotion resulted in lobsters that lost fights and did not secure or retain
      possession of the shelter. In the context of dominance and shelter competition,
      we were unable to demonstrate any advantage of the low dose of exogenous 5
      hydroxytryptamine and a severe disadvantage with the higher dose. Previous
      reports of transient increases in aggression in 5-hydroxytryptamine-treated
      subordinate lobsters did not take into account motor inhibition as a possible
      critical variable in aggression.

PMID- 10947241
TI  - The role of background movement in goldfish vision.
AB  - In experiments described in the literature objects presented to restrained
      goldfish failed to induce eye movements like fixation and/or tracking. We show
      here that eye movements can be induced only if the background (visual surround)
      is not stationary relative to the fish but moving. We investigated the influence
      of background motion on eye movements in the range of angular velocities of 5-20
      degrees s(-1). The response to presentation of an object is a transient shift in
      mean horizontal eye position which lasts for some 10 s. If an object is presented
      in front of the fish the eyes move in a direction such that it is seen more or
      less symmetrically by both eyes. If it is presented at +/-70 degrees from the
      fish's long axis the eye on the side of the object moves in the direction that
      the object falls more centrally on its retina. During these object induced eye
      responses the typical optokinetic nystagmus of amplitude of some 5 degrees with
      alternating fast and slow phases is maintained, and the eye velocity during the
      slow phase is not modified by presentation of the object. Presenting an object in
      front of stationary or moving backgrounds leads to transient suppression of
      respiration which shows habituation to repeated object presentations.

PMID- 10947242
TI  - The otic gasbladder as an ancillary auditory structure in a mormyrid fish.
AB  - Mormyrid fishes use acoustic signals for long-distance communication and a weakly
      electric field for short-distance interaction. Mormyrids are unique in having an
      otic gasbladder attached directly to the saccule on each side of the inner ear.
      Karl von Frisch (1938) hypothesized that the tightly coupled otic gasbladder
      might aid mormyrid hearing. Using the mormyrid fish (Brienomyrus brachyistius),
      this study manipulated gas in the otic gasbladder to test this hypothesis and
      histological sections were made to examine the anatomical relationship between
      the gasbladder and inner ear. The hearing sensitivity curves (audiograms) were
      obtained with the auditory brainstem response protocol. Audiograms were obtained
      from normal fish and from fish in which gas was withdrawn from either one or two
      otic gasbladders. Removal of gas from one otic gasbladder did not result in a
      significant change in either hearing ability or acoustically evoked brainwaves as
      compared to the control fish. Bilateral deflation of the otic gasbladders led to
      significant threshold changes. Histological sections revealed a particularly
      close coupling between the otic gasbladder and the saccule chamber. These results
      support von Frisch's hypothesis that the otic gasbladders of mormyrids assist in
      underwater sound detection.

PMID- 10947244
TI  - Lip cancer in Northern Finland: changing incidence and clinical characteristics.
AB  - A population-based survey was conducted in 35 municipalities in Northern Finland
      to assess the incidence of lip cancer as well as the patient and tumour
      characteristics in cases diagnosed between 1983 and 1997. A total of 96 new
      patients emerged. The age-standardised incidence (per 100,000 years) of lip
      cancer in men decreased from 4.8 in 1983-1987 to 1.4 in 1993-1997. The incidences
      in women were 0.30 to 0.36, respectively. The median age of the patients
      increased from 66 to 73 years through the years. Overall, 90% of the patients had
      at least one of the known risk factors, namely rural domicile, outdoor occupation
      or smoking. The median duration of symptoms also remained the same, as did the
      median size and location of the tumour at diagnosis. In contrast, spread to
      regional lymph nodes became rare during the period.

PMID- 10947243
TI  - Prognostic and predictive factors in oral cancer: the role of the invasive tumour
      front.
AB  - Most decisions for cancer patients are now made on the basis of prognostic and
      predictive factors. However, due to the limited prognostic value of conventional
      tumour/nodal/ metastasis staging and histopathological grading in oral cancer, a
      large group of patients are still over- or under-treated with significant
      personal and socioeconomical impact. Recent work indicates that morphological and
      functional characteristics of the invasive tumour front underlie the biological
      aggressiveness of oral cancer. Incorporation of these concepts into a prognostic
      system will better reflect the biologic diversity of oral cancer and more
      accurately predict clinical outcomes and responses to particular types of
      adjuvant therapy.

PMID- 10947245
TI  - Dissemination of cancer cells into circulation occurs by incisional biopsy of
      oral squamous cell carcinoma.
AB  - To examine whether cancer cell dissemination results from incisional biopsy, we
      tried to detect squamous cell carcinoma (SCC) cells in peripheral blood before
      and after incisional biopsy by means of cytokeratin 19 (CK19) reverse
      transcriptase polymerase chain reaction (RT-PCR). The study population consisted
      of 20 patients with oral SCC; 10 were given incisional biopsies followed by
      radical excision (the incisional biopsy group), and the remaining 10 were treated
      by excisional biopsy alone (the excisional biopsy group). Ten non-oral cancer
      patients with benign oral lesions served as controls. Five-ml blood aspirates
      collected before and after incision were used for CK19 RT-PCR. Two (20.0%) of 10
      patients from the incisional biopsy group were positive for CK19 transcripts in
      their peripheral blood drained 15 min after incision. In contrast, CK19
      transcript was not detected either in the excisional biopsy group or in controls.
      Surgical invasiveness for oral cancer, including incisional biopsy, causes
      dissemination of cancer cells into circulation, resulting in increased risk of
      metastasis.

PMID- 10947246
TI  - Reduction of syndecan-1 expression is associated with dysplastic oral epithelium.
AB  - Syndecans are a family of integral membrane proteoglycans that participate in
      cell-matrix interactions and growth factor binding. Syndecan-1 expression is
      induced during keratinocyte differentiation and reduced in squamous cell
      carcinomas. The purpose of this study was to examine the alteration in syndecan-1
      expression in dysplastic oral epithelium. Sixty-six oral biopsy specimens (43
      epithelial dysplasias, 3 carcinoma in situ and 20 squamous cell carcinomas) were
      studied using immunohistochemical methods. The normal epithelium specimens were
      highly positive for syndecan-1. Fifteen of 46 dysplasias or carcinoma in situ
      specimens showed negative or weak staining for syndecan-1, two of which were
      totally negative. Intermediate and strong staining were observed in 17 and 14
      dysplasias or carcinoma in situ specimens, respectively. Thirteen (65%) squamous
      cell carcinomas showed negative or weak staining for syndecan-1, seven of which
      were totally negative. Only three carcinomas had a strong syndecan-1 expression.
      Four of the 34 patients with dysplasia who were followed up developed squamous
      cell carcinoma. All these dysplasias had weak or totally negative syndecan-1
      expression. The results suggest that the loss of syndecan-1 is associated with
      dysplastic changes in oral epithelium.

PMID- 10947247
TI  - Expression of matrix metalloproteinase-2 in osteoarthritic fibrocartilage from
      human mandibular condyle.
AB  - Matrix metalloproteinase (MMP)-2 is expressed in osteoarthritic cartilage and
      synovial fluid and is thought to be involved in the degradation of cartilage
      extracellular matrix. However, MMP-2 expression and osteoarthritic changes in
      internal derangement of the temporomandibular joint are unknown. In the present
      study, we have examined the histological relationship between osteoarthritic
      changes on articular cartilage with or without articular disc perforation, and
      MMP-2 expression, in 85 mandibular condyles from cadavers. The expression and
      tissue immunolocalization of MMP-2 in fibrocartilages from these condyles was
      examined histochemically. The Mankin grade of histological criteria for specimens
      with disc perforation was significantly higher than that of specimens without
      perforation. MMP-2 immunostaining was positive in the cytoplasm of chondrocytes
      and in their surrounding matrix. There was a linear correlation between MMP-2
      positive cell rates and Mankin grade. Our data suggest that MMP-2 plays an
      important role in fibrocartilage degradation in internal derangement of the
      temporomandibular joint.

PMID- 10947248
TI  - Establishment of a cell line with phenotypes of chondrocyte from a human
      osteogenic sarcoma of the mandible.
AB  - We have succeeded in transplanting a human osteogenic sarcoma of the mandible
      into athymic mice. The transplanted tumor showed marked chondrogenesis and
      mineralization. Recently, a cell line (USAC) with phenotypes of chondrocyte has
      been established from the transplanted tumor. USAC cells were stellate or spindle
      shaped in sparse culture, but polygonal or spherical at sub-confluency to
      confluency. In long-term culture, the cells were condensed and calcified nodules
      were formed. Production of types I, II and X collagen were detected by
      immunohistochemical staining and Western blot analysis. Type I collagen was
      strongly expressed in the stellate or spindle-shaped cells. Although type II
      collagen was usually present in all cells during culture, it was strongly stained
      in polygonal cells at confluency. Type X collagen was seen in large polygonal
      cells around calcified nodules. Marked [35S]-sulfate uptake and metachromasia
      were seen at the confluent stage and in the nodule. The cells around the nodules
      were positive for alkaline phosphatase, and the center of the nodules was stained
      with alizarin red. The potentiality of cartilage formation was confirmed by in
      vivo experiments using a diffusion chamber in athymic mice. These observations
      indicate that USAC cells maintain characteristics of chondrocyte progenitor cells
      and thus may serve as a useful model to study the sequential events of
      chondrogenesis and the process of morbid endochondral calcification. This
      experiment also demonstrated that transplantation of tumor tissue into athymic
      mice is a convenient strategy for establishment of a cell line.

PMID- 10947249
TI  - The prevalence of oral mucosal lesions in a population in Ljubljana, Slovenia.
AB  - The purpose of the present study was to evaluate the prevalence of oral mucosal
      lesions and conditions in a population in Ljubljana, capital of Slovenia. A total
      1609 subjects represented the study population in the survey about the
      periodontal treatment needs in a population in Ljubljana, conducted from 1983 to
      1987. Ten years later the same 1609 subjects were invited to the second
      examination. Altogether, 555 (34.5%) of the invited subjects in the age range 25
      75 years came for an interview and clinical examination at the Department of Oral
      Medicine and Periodontology of the Dental Clinic in Ljubljana. Oral mucosal
      lesions and conditions were evaluated according to the WHO Guide to Epidemiology
      and Diagnosis of Oral Mucosal Diseases and Conditions. The results showed the
      presence of one or more mucosal lesions in 61.6% of the population. Fordyce's
      condition was observed the most frequently (49.7%) followed by: fissured tongue
      (21.1%), varices (16.2%), history of herpes labialis (16.0%), history of
      recurrent aphthae (9.7%), denture stomatitis (4.3%), leukoplakia (3.1%), cheek
      biting (2.7%), lichen planus (2.3%), frictional keratosis (2.2%), geographic
      tongue (2.2%), geographic and fissured tongue together (1.1%), mucocele (0.9%),
      smoker's palate (0.5%) and angular chelitis (0.4%). In the population examined,
      no oral malignancies were observed. Mucosal lesions like whitish lesions, denture
      related lesions, fissured tongue, varices and mucocele were more prevalent with
      increasing age. Tobacco-related lesions (leukoplakia and smoker's palate
      together) were significantly more prevalent among men than among women (P<0.05),
      while lichen planus, denture stomatitis and herpes labialis occurred more
      frequently in the female population.

PMID- 10947251
TI  - Physicists directing training programs should cooperate to align student
      enrollment with market demand for medical physicists.

PMID- 10947250
TI  - Decline in the rate of oral opportunistic infections following introduction of
      highly active antiretroviral therapy.
AB  - In recent years the management of human immunodeficiency virus (HIV)-positive
      individuals has been based on highly active antiretroviral therapy (HAART)
      comprising a combination of nucleoside analogues or the combination of these
      agents with protease inhibitors. The aim of the present study was to describe the
      prevalence of oral lesions in a cohort of 103 HIV-seropositive patients on HAART,
      to compare these data with the prevalence of lesions prior to HAART and to
      correlate these finding with the immunologic data. A total of 103 HIV
      seropositive patients on HAART were selected. Oral lesions associated with HIV
      infection and immunological parameters were registered. On re-examination 6
      months after the first evaluation, 61/103 patients were available. Comparing the
      prevalence of oral lesions before and after the onset of HAART, the number of
      oral lesions was significantly lower (P=0.001). The number of CD4+ cells
      increased and the viral load decreased significantly after initiation of HAART
      (P=0.001 and P= 0.0001). On re-examination 6 months later, the prevalence of
      lesions again decreased significantly (P=0.001). The immunological benefits of
      HAART may prevent HIV-associated oral lesions in patients with advanced HIV
      disease. Our results showed that oral manifestations decrease on HAART, but in
      four patients the immunological effects of therapy did not provide sufficient
      protection against human papillomavirus (HPV)induced lesions.

PMID- 10947252
TI  - Direct measurement of mammographic x-ray spectra using a CdZnTe detector.
AB  - Our purpose is to directly measure mammographic x-ray spectra with collimators
      and a low-efficiency CdZnTe detector developed recently and to find out the best
      fit response function of CdZnTe detector to correct the measured spectra. Photon
      spectra (target Mo or Rh) produced by a mammographic x-ray unit at 25-32 kV and
      240 mAs (= 3 times of 80 mAs) and transmitted through 0.03 mm Mo or 0.025 mm Rh
      filter and object (0.1 mm Al to 0.8 mm Al phantoms) have been analyzed. Since
      detected spectra were distorted by the response of CdZnTe detector and did not
      present the true photon spectra, the correction was applied by the stripping
      procedure. The response function of detector used in this procedure has been
      determined by the evaluation of interactions (K-escape, coherent scattering, and
      Compton scattering processes) and incomplete charge collection calculated using
      the Monte Carlo method. We have used Kalpha1, Kalpha2, Kbeta1, Kbeta2 radiations
      of Cd, Zn, and Te, respectively and have used the weight function for the
      incomplete charge collection and have considered Compton scattering. The Monte
      Carlo simulations were continued by changing the important factors (mean path
      length of hole lambda(h), dead layer of the CZT crystal and weight factor Wq) of
      incomplete charge collection until the best fit response function was found out.
      Corrected photon spectra were compared with the mammographic x-ray spectral data
      of Bureau of Radiological Health (BRH) measured using a Ge detector. Attenuation
      curves of aluminum for 25-32 kV were calculated from the corrected photon spectra
      and compared with the attenuation curves measured using an ionization chamber.
      These results obtained using the CdZnTe detector agreed with the mammographic x
      ray spectral data of BRH and attenuation curves obtained by the ionization
      chamber.

PMID- 10947253
TI  - Improved image quality in digital mammography with image processing.
AB  - PURPOSE: The effect of image processing, specifically Bayesian image estimation
      (BIE), on digital mammographic images is studied. BIE is an iterative, nonlinear
      statistical estimation technique that has previously been used in chest
      radiography to reduce image scatter content and improve the contrast-to-noise
      ratio (CNR). We adapt this technique to digital mammography and examine its
      effect. METHODS/MATERIALS: Images of the American College of Radiologists (ACR)
      breast phantom were acquired on a calibrated digital mammography system at a
      normal mammographic exposure both with and without a grid. An iterative Bayesian
      estimation algorithm was formulated and used to process the images acquired
      without a grid. Quantitative scatter fractions were measured and compared for the
      image acquired with the grid, the image acquired without the grid, and the image
      acquired without the grid and processed by the Bayesian algorithm. CNR values
      were also computed for the four visible masses in the ACR phantom before and
      after processing and compared to a grid. RESULTS: Initial images acquired without
      an antiscatter grid had scatter fractions of 0.46. Processing this image with BIE
      reduced the scatter content to under 0.04. In comparison, the image acquired with
      a grid had scatter of 0.19. BIE processing accounted for CNR improvements from
      29% to 219% for the masses seen in the ACR phantom as compared to the unprocessed
      image. Visibility of the four masses in the phantom was improved. CONCLUSIONS:
      Bayesian image estimation can be used with digital mammography to reduce scatter
      fractions. This technique is very useful as it can reduce scatter content
      effectively without introducing any adverse effects, such as grid line aliasing.
      Bayesian processing can also increase image CNR, which may potentially increase
      the visualization of subtle masses. Preliminary work shows an improvement in CNR
      to values greater than that provided by a standard grid.

PMID- 10947254
TI  - Feature selection and classifier performance in computer-aided diagnosis: the
      effect of finite sample size.
AB  - In computer-aided diagnosis (CAD), a frequently used approach for distinguishing
      normal and abnormal cases is first to extract potentially useful features for the
      classification task. Effective features are then selected from this entire pool
      of available features. Finally, a classifier is designed using the selected
      features. In this study, we investigated the effect of finite sample size on
      classification accuracy when classifier design involves stepwise feature
      selection in linear discriminant analysis, which is the most commonly used
      feature selection algorithm for linear classifiers. The feature selection and the
      classifier coefficient estimation steps were considered to be cascading stages in
      the classifier design process. We compared the performance of the classifier when
      feature selection was performed on the design samples alone and on the entire set
      of available samples, which consisted of design and test samples. The area Az
      under the receiver operating characteristic curve was used as our performance
      measure. After linear classifier coefficient estimation using the design samples,
      we studied the hold-out and resubstitution performance estimates. The two classes
      were assumed to have multidimensional Gaussian distributions, with a large number
      of features available for feature selection. We investigated the dependence of
      feature selection performance on the covariance matrices and means for the two
      classes, and examined the effects of sample size, number of available features,
      and parameters of stepwise feature selection on classifier bias. Our results
      indicated that the resubstitution estimate was always optimistically biased,
      except in cases where the parameters of stepwise feature selection were chosen
      such that too few features were selected by the stepwise procedure. When feature
      selection was performed using only the design samples, the hold-out estimate was
      always pessimistically biased. When feature selection was performed using the
      entire finite sample space, the hold-out estimates could be pessimistically or
      optimistically biased, depending on the number of features available for
      selection, the number of available samples, and their statistical distribution.
      For our simulation conditions, these estimates were always pessimistically
      (conservatively) biased if the ratio of the total number of available samples per
      class to the number of available features was greater than five.

PMID- 10947255
TI  - Implementation of a Tc-99m and Ce-139 scanning line source for attenuation
      correction in SPECT using a dual opposing detector scintillation camera.
AB  - Image degradation during single photon emission computed tomography (SPECT) due
      to attenuation and Compton scatter of photons can cause clinical image artifacts
      and will also result in inaccurate quantitative data. Therefore attenuation
      correction methods recently received wide interest. Transmission imaging can be
      performed to obtain the attenuation coefficients of a nonhomogeneous attenuating
      medium accurately. The aim of this study was firstly to evaluate the imaging
      characteristics of the scanning line source assembly. The results obtained with
      Tc-99m and Ce-139 were compared. Secondly the calculated attenuation coefficients
      were compared with known values from literature, using Tc-99m and Ce-139 as
      transmission sources. Lastly the method of acquiring simultaneous transmission
      and emission data was investigated. This study shows that an attenuation
      coefficient map can be obtained using a scanning line source for transmission
      imaging with a dual opposing detector camera. The imaging characteristics of Tc
      99m and Ce-139 as transmission sources are similar. The resolution obtained with
      the Ce-139 line source was poorer than that obtained with the Tc-99m line source.
      A linear relationship was found between CT numbers and attenuation coefficients
      for transmission images using both Tc-99m and Ce-139 line sources. The
      attenuation coefficient value for water was underestimated by 1% using the Tc-99m
      transmission source and underestimated by 10% using Ce-139 as transmission
      source. This underestimation of attenuation coefficient values was also obtained
      in the human study. A myocardial perfusion study processed without and with
      attenuation correction clearly demonstrated the effect of the attenuation
      correction in the inferior myocardial region. The potential of using a scanning
      line source as transmission source with a dual opposing detector camera has been
      demonstrated in this study. The transmission source, Ce-139 was successfully
      introduced in this investigation for simultaneous acquisition of transmission and
      emission data.

PMID- 10947256
TI  - Design and evaluation of an LSO PET detector for breast cancer imaging.
AB  - Functional imaging with positron emission tomography (PET) may be a promising
      technique in conjunction with x-ray mammography for breast cancer patient
      management. Conventional whole body PET scanners provide metabolic images of
      breast cancer patients with several shortcomings related to the general-purpose
      nature of these systems. In whole body scanners, the detectors are typically 20
      30 cm away from the breast or axilla, reducing sensitivity, and these scanners
      have relatively large detector elements (> 4 mm), limiting spatial resolution.
      Dedicated PET systems for breast imaging aim to overcome these limitations and
      improve the overall diagnostic quality of the images by bringing the detectors
      closer to the area to be imaged, thereby improving sensitivity, and by using
      smaller detector elements to improve the spatial resolution. We have designed and
      developed a modular PET detector that is composed of a 9x9 array of 3x3x20 mm3
      lutetium oxyorthosilicate (LSO) scintillator crystals coupled to an optical fiber
      taper, which in turn is coupled to a Hamamatsu R5900-C8 position-sensitive
      photomultiplier tube. These detectors can be tiled together without gaps to
      construct large area detector arrays to form a dedicated PET breast cancer
      imaging system. Two complete detector modules have been built and tested. All
      detector elements are clearly visualized upon flood irradiation of the module.
      The intrinsic spatial resolution (full-width at half-maximum) was measured to be
      2.26 mm (range 1.8-2.6 mm). The average energy resolution was 19.5% (range 17%
      24%) at 511 keV. The coincidence time resolution was measured to be 2.4 ns. The
      detector efficiency for 511 keV gamma rays was 53% using a 350 keV energy
      threshold. These promising results support the feasibility of developing a high
      resolution, high sensitivity dedicated PET scanner for breast cancer
      applications.

PMID- 10947257
TI  - Methods to determine the fluorescence and Auger spectra due to decay of
      radionuclides or due to a single atomic-subshell ionization and comparisons with
      experiments.
AB  - The aim of this work is to describe methods of determining the fluorescence and
      Auger spectra due to decay of radionuclides or a single atomic-subshell
      ionization. First discussed is the electron vacancy generation in an atomic
      subshell by ionization, internal-conversion decay, or electron-capture decay.
      Later discussed is the status of electron vacancy following emission of
      fluorescence x rays and Auger electrons. Special attention is given to the
      relaxation probabilities and the procedures to calculate energies of released
      electrons. Also discussed are the Monte Carlo and deterministic methods to
      calculate vacancy cascades.

PMID- 10947258
TI  - Absorbed fractions in a voxel-based phantom calculated with the MCNP-4B code.
AB  - A new approach for calculating internal dose estimates was developed through the
      use of a more realistic computational model of the human body. The present
      technique shows the capability to build a patient-specific phantom with
      tomography data (a voxel-based phantom) for the simulation of radiation transport
      and energy deposition using Monte Carlo methods such as in the MCNP-4B code. MCNP
      4B absorbed fractions for photons in the mathematical phantom of Snyder et al.
      agreed well with reference values. Results obtained through radiation transport
      simulation in the voxel-based phantom, in general, agreed well with reference
      values. Considerable discrepancies, however, were found in some cases due to two
      major causes: differences in the organ masses between the phantoms and the
      occurrence of organ overlap in the voxel-based phantom, which is not considered
      in the mathematical phantom.

PMID- 10947259
TI  - Functional magnetic resonance imaging aided radiation treatment planning.
AB  - Functional MRI (magnetic resonance imaging) allows one to noninvasively identify
      various eloquent cortices in the brain. The integration of cortical activation
      information into radiosurgical treatment planning may provide an alternative to
      prevent or minimize radiation damage to eloquent cortex. A novel approach of
      directly integrating the fMRI (functional magnetic resonance imaging) brain map
      into treatment planning is proposed. Three brain tumor patients have been studied
      using this method with motor and/or visual paradigms. Brain activation was
      demonstrated in eloquent cortex at the precentral gyrus (motor area) and medial
      occipital lobe (visual area). The activation maps were transferred to a treatment
      planning workstation, (XKnife), and 3D (three-dimensional) activation maps were
      generated and co-registered to a 3D CT (computed tomography) anatomical data set,
      which provided the calibration localizer, for treatment planning. Radiosurgery
      was designed based on both functional and structural information by the medical
      team consisting of a radiation oncologist, a neurosurgeon and a physicist. The
      average maximum dose for the tumor was 2113 cGy. The average maximum dose for
      tissue surrounding the tumor was 1600 cGy. The average dose with fMRI information
      to the eloquent cortex was 163.4 cGy over three patients, while without fMRI
      information it was 240.5 cGy. The average percentage dose reduction over three
      patients is 32%. The results suggest that using this method can reduce the dose
      to the eloquent cortex. This approach provides the physician with additional
      information for treatment planning and may spare the patient unnecessary
      radiation exposure to adjacent eloquent cortices.

PMID- 10947260
TI  - Inverse planning incorporating organ motion.
AB  - Accurate targeting is important in intensity-modulated radiation therapy (IMRT).
      The positional uncertainties of structures with respect to the external beams
      arise in part from random organ motion and patient setup errors. While it is
      important to improve immobilization and reduce the influence of organ motion, the
      residual effects should be included in the IMRT plan design. Current inverse
      planning algorithms follow the conventional approach and include uncertainties by
      assuming population-based margins to the target and sensitive structures. Margin
      around a structure represents a "hard boundary" and the fact that a structure has
      a spatial probability distribution has been completely ignored. With increasing
      understanding of spatial uncertainties of structures and the technical capability
      of fine-tuning the dose distribution on an individual beamlet level in IMRT, it
      seems timely and important to fully utilize the information in the planning
      process. This will reduce the "effective" margins of the structures and
      facilitate dose escalation. Instead of specifying a "hard margin," we describe an
      inverse planning algorithm which takes into consideration positional uncertainty
      in terms of spatial probability distribution. The algorithm was demonstrated by
      assuming that the random organ motion can be represented by a three-dimensional
      Gaussian distribution function. Other probability distributions can be dealt with
      similarly. In particular, the commonly used "hard margin" is a special case of
      the current approach with a uniform probability distribution within a specified
      range. The algorithm was applied to plan treatment for a prostate case and a
      pancreatic case. The results were compared with those obtained by adding a margin
      to the clinical target volume. Better sparing of the sensitive structures were
      obtained in both cases using the proposed method for approximately the same
      target coverage.

PMID- 10947261
TI  - Photon dose calculation of a three-dimensional treatment planning system compared
      to the Monte Carlo code BEAM.
AB  - The purpose of this work is to compare the photon dose calculation of a
      commercially available three-dimensional (3D) treatment planning system based on
      the collapsed cone convolution technique against BEAM, a Monte Carlo code that
      allows detailed simulation of a radiotherapy accelerator. The first part of the
      work is devoted to the commissioning of BEAM for a 6 MV photon beam and to the
      optimization of the linac description to fit the experimental data. This step
      also involves a comparison with radiochromic film data on an inhomogeneous
      phantom built to simulate electronic nonequilibrium conditions. Commissioning the
      selected photon beams required a careful description of the treatment head and
      the fine tuning of physical parameters such as electron beam energy and radius.
      The second part shows the dose comparison for real patient's CT data sets: A
      mediastinal treatment and a breast treatment were simulated. Doses in terms of
      absolute values per monitor unit were calculated based on the BEAM simulation of
      the CT data sets. For comparisons of real-patient cases, differences between the
      treatment planning system and BEAM ranged from 0 to 2.6% and were within +/-2
      standard deviations for the dose calculated at the prescription point. Dose
      volume histogram analysis indicated that there is no consistent difference
      between the Monte Carlo and the convolution calculations. On the basis of the
      results presented in this study, we can conclude that the CCC algorithm is
      capable of giving results absolutely comparable to those of a Monte Carlo
      calculation, as far as common 3D radiotherapy planning is concerned.

PMID- 10947262
TI  - Quality assurance for a treatment planning system in scanned ion beam therapy.
AB  - Conformal radiation therapy using dynamic beam delivery systems like scanned ion
      beams requires concise quality assurance procedures for the complete treatment
      planning process. For the heavy ion therapy facility at GSI, Darmstadt, a quality
      assurance program for the treatment planning system (TPS) has been developed. It
      covers the development and updating of software, data protection and safety, and
      the application of soft- and hardware. The tests also apply to the geometrical
      precision of imaging devices and the geometrical and dosimetrical verification of
      dose distributions in different phantoms. The quality assurance program addresses
      acceptance and constancy tests of the treatment planning program. Results of the
      acceptance tests served as a basis for its governmental approval. Two main
      results of the acceptance tests are representative for the overall performance of
      the system. (1) The geometrical uncertainty that could be achieved for the target
      point definition, setup accuracy, field contouring, and field alignment is
      typically 1.5 mm. The uncertainty for the setup verification using digitally
      reconstructed radiographs (DRR's) is limited to 2 mm. (2) The mean deviations
      between measured and planned dose values is 3% for standardized cases in a water
      phantom and up to 6% for more complicated treatment configurations.

PMID- 10947263
TI  - Leaf position verification during dynamic beam delivery: a comparison of three
      applications using electronic portal imaging.
AB  - The use of a dynamic multileaf collimator (MLC) to deliver intensity-modulated
      beams presents a problem for conventional verification techniques. The use of
      electronic portal imaging to track MLC leaves during beam delivery has been shown
      to provide a solution to this problem. An experimental comparison of three
      different verification systems, each using a different electronic portal imaging
      technology, is presented. Two of the systems presented are commercially available
      imagers with in-house modifications, with the third system being an in-house
      built experimental system. The random and systematic errors present in each of
      the verifications systems are measured and presented, together with the study of
      the effects of varying dose rate and leaf speed on verification system
      performance. The performance of the three systems is demonstrated to be very
      similar, with an overall accuracy in comparing measured and prescribed collimator
      trajectories of approximately +/-1.0 mm. Systematic errors in the percentage
      delivered dose signal provided by the accelerator are significant and must be
      corrected for good performance of the current systems. It is demonstrated that,
      with suitable modifications, commercially available portal imaging systems can be
      used to verify dynamic MLC beam delivery.

PMID- 10947264
TI  - Improvement of tomographic intensity modulated radiotherapy dose distributions
      using periodic shifting of arc abutment regions.
AB  - Based on the study of treatment arc positioning versus target length, a method
      that allowed periodic shift of arc abutment regions through the course of
      intensity modulated radiotherapy (IMRT) was developed. In this method, two
      treatment plans were developed for the same tumor. The first plan contained the
      original target (Planning Target Volume as defined by radiation oncologist) and
      the second one contained a modified target. The modification of the original
      target consisted of simply increasing its length, adding a small extension to it,
      or creating a distant pseudo target. These modifications cause arc abutment
      regions in the second plan to be shifted relative to their positions in the first
      plan. Different methods of target modification were investigated because in some
      cases (for instance, when a critical structure might overlap with the target
      extension) a simple extension of the target would cause an unacceptable
      irradiation of the sensitive structures. The dose prescribed to the modified
      portion of the target varied from 10% to 100% of the original target dose. It was
      found that a clinically significant shift (> or =5 mm) in abutment region
      locations occurred when the dose prescribed to the extended portion of the target
      was > or =95% of the original target dose. On the other hand, the pseudo target
      required only approximately 10% to 20% of the original target dose to produce the
      same shift in arc positions. Results of the film dosimetry showed that when a
      single plan was used for the treatment delivery, the dose nonuniformity was 17%
      and 25% of the prescribed dose with 0.5 and 1 mm errors in couch indexing,
      respectively. The dose nonuniformity was reduced by at least half when two plans
      were used for IMRT delivery.

PMID- 10947265
TI  - Intensity modulated radiotherapy dose delivery error from radiation field offset
      inaccuracy.
AB  - In Intensity Modulated Radiotherapy (IMRT), irradiation is delivered in a number
      of small aperture subfields. The fluences shaped by these small apertures are
      highly sensitive to inaccuracies in multileaf collimator (MLC) calibration. The
      Radiation Field Offset (RFO) is the difference between a radiation and a light
      field at the Source to Axis Distance (SAD) for a MLC. An Intensity Modulated
      Radiotherapy (IMRT) system must incorporate a RFO by closing in all leaf
      openings. In IMRT, RFO inaccuracy will result in a dose error to the interior of
      a target volume. We analyze dosimetric consequences of incorporating a wrong RFO
      into the CORVUS, 1 cm x 1 cm, step and shoot, IMRT system. The following method
      was employed. First an IMRT plan is generated for a target volume in a phantom,
      which produces a set of dynamic MLC (DMLC) files with the correct RFO value. To
      simulate delivery with a wrong RFO value, we wrote a computer code that reads in
      the DMLC file with the correct RFO value and produces another DMLC with an
      incorrect RFO specified by a user. Finally the phantom was irradiated with the
      correct and the incorrect RFO valued DMLC files, and the doses were measured with
      an ionization chamber. The method was applied to 9 fields, 6 MV, IMRT plans. We
      measured Dose Error Sensitivity Factor (DESF) for each plan, which ranged from (0
      8)% mm(-1). The DESF(x) is defined as a fractional dose error to a point (x) in a
      target volume per mm of the RFO error, i.e., DESF(x) is equivalent to
      ?deltaD(x)/D(x)deltaRFO?. Therefore, we concluded that for CORVUS, 6 MV, 1 cm x 1
      cm, step and shoot IMRT, RFO must be determined within an accuracy of 0.5 mm if a
      fractional dose error to a target volume is to be less than 4%. We propose an
      analytic framework to understand the measured DESF's. From the analysis we
      conclude that a large DESF was associated with an DMLC file with small average
      leaf openings. For 1 cm x 1 cm, step and shoot IMRT, the largest possible DESF is
      predicted to be 20% mm(-1). In addition, we wrote computer code that can
      calculate a DESF of a DMLC file. The code was written in Mathematica 3.0. The
      code can be used to screen patient IMRT plans that are highly sensitive to a RFO
      error.

PMID- 10947266
TI  - Dynamic and omni wedge implementation on an Elekta SL linac.
AB  - The concommitant use of a multileaf collimator (MLC) and a wedge can result in
      conflicts in the optimal collimator angle if both MLC and wedge are fixed
      relative to one another. This is particularly true of linacs in which a single
      wedge orientation is provided. In this paper, a solution is provided that makes
      use of two orthogonal universal wedges (omni wedge). Although this technique can
      be applied regardless of the means by which the wedged fields are implemented,
      the measurements reported in this paper were performed using a fixed, internal
      mechanical wedge coupled with a dynamic wedge, formed by the motion of one of the
      backup jaws. An implementation of a dynamic wedge for the Elekta SL series of
      linear accelerators is presented. Results of measurements of the dosimetric
      characteristics of both the particular implementation of the dynamic wedge and of
      the omni field are presented. For the dynamic wedge, measurements were made of
      the wedge factor and dose profile as a function of field size and depth. In
      addition, the effects of variables, such as dynamic delivery technique and
      direction of diaphragm motion, on the dynamic wedge profiles were studied and
      discussed. For the omni wedge, measurements were made of the degree to which the
      mathematical formalism for describing an omni wedge matches the measured isodose
      distributions. Comparisons between mechanical wedge dose distributions and the
      omni wedge were also made.

PMID- 10947267
TI  - Implementation and verification of virtual wedge in a three-dimensional
      radiotherapy planning system.
AB  - Virtual Wedge (VW) is a Siemens treatment modality which generates wedge-shaped
      dose distributions by moving a collimator jaw from closed to open at a constant
      speed while varying the dose rate in every 2 mm jaw position. In this work, the
      implementation and verification of VW in a radiotherapy treatment planning (RTP)
      system is presented. The VW implementation models the dose delivered by VW using
      the Siemens monitor units (MU) analytic formalism which determines the number of
      MU required to generate a wedge-fluence profile at points across the VW beam. For
      any set of treatment parameters, the VW algorithm generates an "intensity map"
      that is used to model the modification of fluence emanating from the collimator.
      The intensity map is calculated as the ratio of MU delivered on an axis point,
      divided by the monitor units delivered on the central-axis MU(0). The dose
      calculation is then performed using either the Clarkson or Convolution/
      Superposition algorithms. The VW implementation also models the operational
      constraints for the delivery of VW due to dose rate and jaw speed limits. Dose
      verifications with measured profiles were performed using both the Clarkson and
      Convolution/Superposition algorithms for three photon beams; Siemens Primus 6 and
      23 MV, and Mevatron MD 15 MV. Agreement within 2% or 2 mm was found between
      calculated and measured doses, over a large set of test cases, for 15, 30, 45,
      and 60 degree symmetric and asymmetric VW fields, using the manufacturer's
      supplied mu and c values for each beam.

PMID- 10947268
TI  - Comparison of dosimetry calibration factors at the NRCC and the NIST. National
      Research Council of Canada. National Institute of Standards and Technology.
AB  - In early 1998, three transfer ionization chambers were used to compare the air
      kerma and absorbed-dose-to-water calibration factors measured by the National
      Research Council of Canada (NRCC) and the National Institute of Standards and
      Technology (NIST). The ratios between the NRCC and NIST calibration factors are
      0.9950 and 1.0061 in the case of the absorbed-dose-to-water and air-kerma
      standards, respectively. In the case of the standard of absorbed dose to water,
      the combined uncertainty of the ratio between the standards of the two
      laboratories is about 0.6% and consequently, the observed difference of 0.5% is
      not significant at the one sigma level. In the case of the standard of air kerma,
      the combined uncertainty of the ratio between the standards of the two
      laboratories is about 0.4%, and so the observed difference of 0.61% is
      significant at the one sigma level. However, this discrepancy is due to the known
      differences in the methods of assessing the wall correction factor at the two
      laboratories. Taking into account changes implemented in the standards that form
      the basis of the calibrations, the present results are consistent with those of
      the previous comparison done in 1990/91. As a direct result of these differences
      in the calibration factors, changing from an air-kerma based protocol following
      TG-21 to an absorbed-dose-to-water based protocol following TG-51, would alter
      the relationship between clinical dosimetry in Canada and the United States by
      about 1%. For clinical reference dosimetry, the change from TG-21 to TG-51 could
      result in an increase of up to 2% depending upon the ion chamber used, the
      details of the protocol followed and the source of traceability, either NRCC or
      NIST.

PMID- 10947269
TI  - Radiochromic film dosimetry of a low energy proton beam.
AB  - In this work some dosimetric characteristics of MD-55-2 GafChromic films were
      studied in a low energy proton beam (21.5 MeV) directly in a water phantom. The
      nonlinearity of the optical density was quantified by a factor P(lin). A
      correction factor P(en), that accounts for optical density dependence on the
      energy, was empirically determined. The effects of detector thickness in depth
      dose measurements and of the film orientation with respect to beam direction were
      investigated. The results show that the MD-55-2 films provide dose measurements
      with the films positioned perpendicularly to the proton beam. A dosimetric
      formalizm is proposed to determine the dose to water at depth d, with films
      oriented perpendicularly to the beam axis. This formalism uses a calibration
      factor of the radiochromic film determined directly on the proton beam at a
      reference depth in water, and the P(lin) factor, that takes into account the
      nonlinearity of the calibration curve and the P(en) factor that, in turn takes
      into account the change of proton beam energy in water. The MD-55-2 films with
      their high spatial resolution and the quasiwater equivalent material are
      attractive, positioned perpendicularly along the beam axis, for the absolute dose
      determination of very small beam sizes and modulated proton beams.

PMID- 10947270
TI  - Detecting electron beam energy shifts with a commercially available energy
      monitor.
AB  - Routine electron beam quality assurance requires an accurate, yet practical,
      method of energy characterization. Subtle shifts in beam energy may be produced
      by the linac bending magnet assembly, and the sensitivity of a commercially
      available electron beam energy-monitoring device for monitoring these small
      energy drifts has been evaluated. The device shows an 11% change in signal for a
      2 mm change in the I50 energy parameter for low energy electron beams (in the
      vicinity of 6 MeV) and a 2.5% change in signal for a 2 mm change in the I50
      energy parameter for high energy electron beams (in the vicinity of 22 MeV). Thus
      the device is capable of detecting small energy shifts resulting from bending
      magnet drift for all clinically relevant electron beams.

PMID- 10947271
TI  - Physics study of microbeam radiation therapy with PSI-version of Monte Carlo code
      GEANT as a new computational tool.
AB  - Microbeam radiation therapy (MRT) is a currently experimental method of
      radiotherapy which is mediated by an array of parallel microbeams of synchrotron
      wiggler-generated x-rays. Suitably selected, nominally supralethal doses of x
      rays delivered to parallel microslices of tumor-bearing tissues in rats can be
      either palliative or curative while causing little or no serious damage to
      contiguous normal tissues. Although the pathogenesis of MRT-mediated tumor
      regression is not understood, as in all radiotherapy such understanding will be
      based ultimately on our understanding of the relationships among the following
      three factors: (1) microdosimetry, (2) damage to normal tissues, and (3)
      therapeutic efficacy. Although physical microdosimetry is feasible, published
      information on MRT microdosimetry to date is computational. This report describes
      Monte Carlo-based computational MRT microdosimetry using photon and/or electron
      scattering and photoionization cross-section data in the 1 eV through 100 GeV
      range distributed publicly by the U.S. Lawrence Livermore National Laboratory
      (LLNL) in the 1990s. These are compared with Monte Carlo-based microdosimetric
      computations using a code and physical data available in the 1980s. With the aim
      of using the PSI-version of GEANT Monte Carlo code for future macro- and
      micro/nano-dosimetric studies of Microbeam Radiation Therapy (MRT) a comparison
      of this code is made with the INHOM(EGS4) (version 1990), Dilmanian-CPE and
      Persliden-CPE Monte Carlo photon-electron codes (both version 1990) with which
      the absorbed dose distributions were calculated in 1990 and 1991 considering, (a)
      a single cylindrical microbeam, (b) multiple cylindrical microbeams in an
      orthogonal square bundle, and (c) multiple planar microbeams. It is shown that
      the PSI-version of GEANT can potentially deliver more accurate results (a) using
      presently the most advanced atomic data, and especially (b) employing "Single
      collision" electron transport instead of only the "Condensed-history" electron
      transport as in code INHOM(EGS4). In contrast Dilmanian-CPE and Persliden-CPE
      codes deposit the electron energy locally instead of transporting it to the
      correct position.

PMID- 10947272
TI  - Measurement of radiotherapy x-ray skin dose on a chest wall phantom.
AB  - Sufficient skin dose needs to be delivered by a radiotherapy chest wall treatment
      regimen to ensure the probability of a near surface tumor recurrence is
      minimized. To simulate a chest wall treatment a hemicylindrical solid water
      phantom of 7.5 cm radius was irradiated with 6 MV x-rays using 20x20 cm2 and
      10x20 cm2 fields at 100 cm source surface distance (SSD) to the base of the
      phantom. A surface dose profile was obtained from 0 to 180 degrees, in 10 degrees
      increments around the circumference of the phantom. Dosimetry results obtained
      from radiochromic film (effective depth of 0.17 mm) were used in the
      investigation, the superficial doses were found to be 28% (of Dmax) at the 0
      degrees beam entry position and 58% at the 90 degrees oblique beam position.
      Superficial dose results were also obtained using extra thin thermoluminescent
      dosimeters (TLD) (effective depth 0.14 mm) of 30% at 0 degrees, 57% at 90
      degrees, and a metal oxide semiconductor field effect transistor (MOSFET)
      detector (effective depth 0.5 mm) of 43% at 0 degrees, 62% at 90 degrees. Because
      the differences in measured superficial doses were significant and beyond those
      related to experimental error, these differences are assumed to be mostly
      attributable to the effective depth of measurement of each detector. We
      numerically simulated a bolus on/bolus off technique and found we could increase
      the coverage to the skin. Using an alternate "bolus on," "bolus off" regimen, the
      skin would receive 36.8 Gy at 0 degrees incidence and 46.4 Gy at 90 degrees
      incidence for a prescribed midpoint dose of 50 Gy. From this work it is evident
      that, as the circumference of the phantom is traversed the SSD increases and
      hence there is an inverse square fluence fall-off, this is more than offset by
      the increase in skin dose due to surface curvature to a plateau at about 90
      degrees. Beyond this angle it is assumed that beam attenuation through the
      phantom and inverse square fall-off is causing the surface dose to reduce.

PMID- 10947273
TI  - Radiation injury from x-ray exposure during brachytherapy localization.
AB  - Two patients developed skin ulcers secondary to high doses of diagnostic-energy x
      rays received during localization procedures as part of brachytherapy treatments.
      Both were morbidly obese and diabetic. The obesity led to the delivery of
      estimated skin doses of 83 Gy in one case and 29 Gy in the other in attempts to
      produce readable images on localization radiographs. This report discusses the
      factors leading to the injuries, the progression of the injuries over time, and
      the variables involved in the localization procedures with the aim of preventing
      future mishaps. The greatest contribution to the large skin dose was the need,
      with the equipment available, to use multiple exposures to produce a single film,
      because of the effect of the resultant reciprocity failure.

PMID- 10947274
TI  - An investigation of the feasibility of gadolinium for neutron capture
      synovectomy.
AB  - Neutron capture synovectomy (NCS) has been proposed as a possible treatment
      modality for rheumatoid arthritis. Neutron capture synovectomy is a two-part
      modality, in which a compound containing an isotope with an appreciable thermal
      neutron capture cross section is injected directly into the joint, followed by
      irradiation with a neutron beam. Investigations to date for NCS have focused on
      boron neutron capture synovectomy (BNCS), which utilizes the 10B(n,alpha)7Li
      nuclear reaction to deliver a highly localized dose to the synovium. This paper
      examines the feasibility of gadolinium, specifically 157Gd, as an alternative to
      boron as a neutron capture agent for NCS. This alternative modality is termed
      Gadolinium Neutron Capture Synovectomy, or GNCS. Monte Carlo simulations have
      been used to compare 10B and 157Gd as isotopes for accelerator-based NCS. The
      neutron source used in these calculations was a moderated spectrum from the
      9Be(p,n) reaction at a proton energy of 4 MeV. The therapy time to deliver the
      NCS therapeutic dose of 10000 RBE-cGy, is 27 times longer when 157Gd is used
      instead of 10B. The skin dose to the treated joint is 33 times larger when 157Gd
      is used instead of 10B. Furthermore, the impact of using 157Gd instead of 10B was
      examined in terms of shielded whole-body dose to the patient. The effective dose
      is 202 mSv for GNCS, compared to 7.6 mSv for BNCS. This is shown to be a result
      of the longer treatment times required for GNCS; the contribution of the high
      energy photons emitted from neutron capture in gadolinium is minimal. Possible
      explanations as to the relative performance of 157Gd and 10B are discussed,
      including differences in the RBE and range of boron and gadolinium neutron
      capture reaction products, and the relative values of the 10B and 157Gd thermal
      neutron capture cross section as a function of neutron energy.

PMID- 10947275
TI  - Reply to "Comment on 'On the beam quality specification of high-energy photons
      for radiotherapy dosimetry' " [Med. phys. 27, 441-444 (2000)].

PMID- 10947276
TI  - The mystery of psaA and penicillin tolerance in Streptococcus pneumoniae.

PMID- 10947278
TI  - Deciphering lying eyes. Brains without words.

PMID- 10947277
TI  - Germs and sickness in a shrinking world. Are humans and beasts too close for
      comfort?

PMID- 10947279
TI  - Prostate dilemmas. Early detection is forcing more men to weigh the difficult
      treatment options.

PMID- 10947280
TI  - Point of care medicine will once again reshape radiology's landscape.

PMID- 10947281
TI  - Proper management of capitated contract requires the right tools.

PMID- 10947282
TI  - Nonspecific findings confound screening for breast cancer.

PMID- 10947283
TI  - Interventionalists invade new territory with research agenda.

PMID- 10947284
TI  - R&D partnerships.

PMID- 10947285
TI  - Top 10 telemedicine programs for 1999: experience pays off.

PMID- 10947286
TI  - Needle design gives boost to thermal ablation.

PMID- 10947287
TI  - Documentation tips for reducing malpractice risk.

PMID- 10947288
TI  - A model for successful rural practice.

PMID- 10947289
TI  - Helping patients take charge of their chronic illnesses.

PMID- 10947290
TI  - Linking Internet strategy to high-quality, cost-effective managed care.
AB  - This article describes an experimental pilot project incorporating e-commerce and
      the Internet into the traditional process of health benefit negotiations through
      the utilization of an HMO Internet auction. The timeline and process of the
      auction are described, with the final auction taking place during the last week
      of negotiations. The results reveal an efficient and effective system to augment
      the traditional benefit negotiation process.

PMID- 10947291
TI  - Controlling human capital costs in the new millennium.
AB  - Low productivity and high turnover can be more costly to employers than insurance
      premiums and medical claims. This article discusses the need for coordinated
      management of all behavioral health benefits. It provides two case studies that
      illustrate how such coordination can avert possible long-term costs and loss of a
      valued employee.

PMID- 10947292
TI  - Employers and health plans: purposeful partnerships.
AB  - This article discusses the advantages of developing a partnership between the
      employer and the health benefit vendor. The author explains that there are three
      types of employer/vendor relationships ranging from the minimal transaction based
      to the value based and finally to a partnership-based arrangement. Success
      depends upon whether the chosen relationship strategy supports the business
      objectives, organizational culture and effective plan execution.

PMID- 10947293
TI  - Benefit cost management in the new millennium.
AB  - The new millennium will bring new challenges to managing employee benefit plans.
      Costs are going up. The provider community is consolidating. The Consolidated
      Omnibus Budget Reconciliation Act of 1985 (COBRA) and the Health Insurance
      Portability and Accountability Act of 1996 (HIPAA) have added cost and complexity
      to benefit plans. Employers expect strategic partnering and a high degree of
      flexibility while simultaneously reducing benefit managers' budgets and staff.
      This article provides specific strategies and tactics for managing benefit costs
      in this new era.

PMID- 10947294
TI  - Leaving an unethical managed care plan: an exploratory look at doctors'
      intentions.
AB  - To address the problems of unnecessary care and limited resources, managed care
      health insurance programs have become commonplace. With managed care programs,
      however, physicians are facing increasing pressures. This article briefly
      considers four ethical situations that doctors face under managed care systems.
      The article surveys a national random sample of general practitioners and
      surgeons to determine how doctors would respond to these dilemmas and the extent
      to which exposure to such situations influences them to leave a managed care
      plan.

PMID- 10947295
TI  - Changes in the HMO marketplace and the new role of consumers.
AB  - The HMO marketplace is becoming increasingly dominated by two organizational
      structures: the network or mixed model and the IPA model. Combined, these two HMO
      structures represent over 80% of all plans. Both of these plan types tend to be
      decentralized and diverse, causing separation of ownership and control. This
      article uses agency theory to examine various control mechanisms including the
      involvement of the consumer.

PMID- 10947296
TI  - Managing the demand for health services by adopting patient-centered programs.
AB  - Recently, the trend to managing the demand of health care services has become
      more prevalent. Standalone types of demand management programs are patient
      centered and support appropriate health care decision making by the consumer. The
      author examines these types of programs including their benefits and risks.

PMID- 10947297
TI  - Empowering the managed care consumer: not as easy as it sounds.
AB  - Managed care remains one of the most highly publicized issues in employee
      benefits, with its accompanying controversy causing concern to the consumer and
      the employer. The authors of this article discuss the very basic things consumers
      of health benefits should know about their plans in order to be prepared, as well
      as what they should reasonably expect from employers that sponsor the plans.

PMID- 10947298
TI  - Bridging decision analytic modelling with a cross-sectional study. Application to
      Parkinson's disease.
AB  - The ideal study design for demonstrating the possible health outcomes and costs
      associated with a new drug would be a naturalistic prospective study. However, it
      is not often feasible to derive the required information from scientifically
      sound prospective studies. In these cases, decision analytic models may provide
      some of the missing information. However, the use of a Delphi panel to gather
      data for these models is a major concern because of potential bias and data
      accuracy. Because reimbursement of pharmaceuticals is often based on economic
      data derived from modelling studies, it is obvious that potential bias due to the
      use of Delphi panels should be minimised. In this manuscript we present an
      alternative data source for modelling studies: the cross-sectional study. Data
      from such studies can be used to yield costs and utilities for Markov health
      states. The overall combined design may be considered a hybrid between a
      naturalistic prospective study and a modelling study by maximising the pros and
      minimising the cons of both types of design, including an increase of external
      validity. This hybrid design is based on bridging the probabilities derived from
      the literature and clinical trials with information on costs and utilities from a
      cross-sectional study. This design also has logistical advantages, namely a
      shorter required study duration compared with prospective naturalistic studies
      for chronic diseases. This combined design was illustrated using a Markov model
      for Parkinson's disease.

PMID- 10947299
TI  - ACE inhibitors after myocardial infarction. Clinical and economic considerations.
AB  - Economic analysis has been extensively used to guide the use of ACE inhibitors in
      chronic heart failure. More recently, it has been used to guide the use of ACE
      inhibitors after myocardial infarction. The results of major clinical trials
      leave us in no doubt that ACE inhibitors are useful in the treatment of patients
      after myocardial infarction. The results of economic analysis unanimously
      indicate that ACE inhibitors are cost effective when used to treat patients after
      myocardial infarction. Any comparison of the different treatment strategies
      available suggests that all are comparably cost effective and argues for the
      widest possible use of ACE inhibitors in this setting. The evidence suggests
      that, in this context as in so many others, ACE inhibitors remain under-utilized.

PMID- 10947301
TI  - Evaluating the potential 'economic attractiveness' of new therapies in patients
      with non-ST elevation acute coronary syndrome.
AB  - OBJECTIVE: To evaluate the relationship between how much a new cardiovascular
      therapy improves clinical outcomes over current therapies and how much more it
      can cost while still remaining 'economically attractive'. DESIGN: We developed a
      decision model to predict the 6-month cumulative cost savings and increased life
      expectancy that could be associated with new therapies for patients with non-ST
      elevation acute coronary syndrome. SETTING: This modelling study used outcome and
      cost data from US sources. METHODS: Event probabilities at 30 days and 6 months
      were estimated from US patients with non-ST elevation in the Global Use of
      Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO)
      IIb trial; cost estimates were derived from patients enrolled in the Economics
      and Quality of Life substudy of this trial. Patient life expectancy estimates
      were calculated using survival estimates for similar patients treated at Duke
      University Medical Center. RESULTS: We found that new therapies costing up to
      $US2000 per episode that reduce 6-month mortality by 0.5%, death and nonfatal
      myocardial infarction (MI) by 1%, or death, nonfatal MI and revascularisation by
      3%, may be cost effective by current standards. When new therapies costing up to
      $US1000 per episode reduce the absolute rate of death, nonfatal MI and
      revascularisation at 6 months by 6.5% or more, they may be cost saving.
      CONCLUSION: Our analysis suggests that economic constraints should not inhibit
      the development of effective new therapies.

PMID- 10947302
TI  - Assessing health utilities in schizophrenia. A feasibility study.
AB  - BACKGROUND: Utility, a concept derived from economics, is the desirability or
      preference that individuals exhibit for a certain health state. Utility
      measurement could be viewed as an alternative means of appraising the quality of
      life of individuals affected by a chronic illness such as schizophrenia.
      Traditional techniques of utility measurement involve 2 steps: (i) identifying
      the different health states experienced by individuals during the course of an
      illness; and (ii) assigning them numerical values known as utilities. AIM: The
      study examined the feasibility issues and psychometric aspects of obtaining
      accurate health state descriptions and their utilities from symptomatically
      stable patients with schizophrenia. METHODS: The study used a cross-sectional,
      case-controlled design, with a study group consisting of 120 clinically
      stabilised patients with schizophrenia and a control group of 32 treated and
      recovered patients with major depression. Patients were asked to provide detailed
      descriptions of 3 distinct health states associated with their illness: current
      state, worst state experienced since the onset of illness and a perfect state
      desired in the future. Further, patients were asked to assign utilities to these
      health states with the aid of a purpose-built evaluation protocol comprising
      Magnitude Estimation (ME), Rating Scale (RS), Standard Gamble (SG), Time Trade
      Off (TTO) and Willingness-to-Pay (WTP) techniques. The battery was repeated after
      a 1-week interval. Independent raters assessed symptom severity, insight and
      quality of life, and nurse-clinicians involved in their care were asked to
      provide the utility ratings of their clients' mental health state. Patients'
      opinions about the acceptability of utility measurement techniques, and the
      respondent burden were also ascertained. RESULTS: Compared with control patients
      with treated depression, patients with schizophrenia were able to distinguish and
      describe the specified health states with an equal degree of ease and accuracy.
      RS, TTO and WTP techniques emerged as the favoured methods of utility evaluation.
      The test-retest reliability of utility ratings (r = 0.87 to 0.97; p < 0.001) was
      high, and concurrent validity with the quality of life measures was acceptable.
      Reliability and validity of patients' appraisals were unaffected by symptoms
      severity and insight. The accuracy of nurse-clinicians' appraisals were dependent
      on their close familiarity with the patients and their illness. CONCLUSION:
      Clinically stabilised patients with schizophrenia can provide accurate health
      state descriptions and assign them utilities with a fair degree of reliability
      and validity. Utility evaluations based on patients' self-appraisals can be seen
      as potential tools in outcome studies and clinical trials involving patients with
      schizophrenia, but the methodology requires further refinement to accommodate the
      limitations imposed by the patients' disturbed mental status.

PMID- 10947303
TI  - Economics of the antithymocyte globulins Thymoglobulin and Atgam in the treatment
      of acute renal transplant rejection.
AB  - OBJECTIVE: To evaluate the economic implications for transplant centres, Medicare
      and society of treatment of corticosteroid-resistant Banff Grades I, II and III
      acute kidney transplant rejection with the antithymocyte globulins Thymoglobulin
      or Atgam. DESIGN AND SETTING: This was a cost analysis of a randomised double
      blind multicentre clinical trial comparing the safety and efficacy of
      Thymoglobulin and Atgam that was performed at 25 centres in the US in 1994 to
      1996. PATIENTS AND PARTICIPANTS: The study enrolled 163 patients, 82 in the
      Thymoglobulin arm and 81 in the Atgam arm. METHODS: Estimates of the cost of care
      from the initiation of rejection therapy to 90 days post-therapy were derived
      from various publicly available sources and applied to patient-specific clinical
      events documented in the clinical trial. Patients received either intravenous
      Thymoglobulin (1.5 mg/kg/day) for an average of 10 days or intravenous Atgam (15
      mg/kg/day) for an average of 9.7 days. RESULTS: On average, Thymoglobulin
      provided significant cost savings compared with Atgam from the perspective of
      society [$US5977 (1996 values); 95% confidence interval (CI) $US3719 to $US8254],
      Medicare ($US4967; 95% CI $US3256 to $US6678) and the transplant centre ($US3087;
      95% CI $US1512 to $US4667). The overall advantage attributable to Thymoglobulin
      was primarily due to savings from fewer recurrent rejection treatments and less
      frequent return to dialysis. CONCLUSIONS: Treatment of acute renal transplant
      rejection with Thymoglobulin is a cost saving strategy when compared with
      treatment with Atgam.

PMID- 10947300
TI  - Clinical and economic factors important to anaesthetic choice for day-case
      surgery.
AB  - Clinical and economic factors that are important to consider when selecting
      anaesthesia for day-case surgery can differ from those for inpatient anaesthesia.
      Patients undergoing day-case surgery tend to be healthier and have shorter
      durations of surgery. They expect less anxiety before surgery, amnesia for the
      surgical experience, a rapid return to normal (normal mentation with minimal pain
      and nausea) after surgery, and lower expenses. However, the latter 2 expectations
      can conflict; older generic drugs have lower acquisition costs but often impose
      longer recovery times. Longer recovery periods can increase costs by prolonging
      the time to discharge from labour-intensive areas such as the operating suite or
      the post-anaesthesia recovery unit. The challenge for today's anaesthetist is to
      use newer drugs judiciously to minimise their expense without compromising the
      rate or quality of recovery. Several approaches can secure these aims. Most apply
      the least anaesthetic needed. 'Least anaesthetic' may mean the particular form of
      anaesthetic (e.g. local infiltration with monitored anaesthesia care versus a
      general anaesthetic), or may mean the delivery of the smallest effective dose,
      perhaps guided by anaesthetic monitors such as end-tidal analysers or the
      bispectral index. For patients requiring general anaesthesia, a combination of
      several drugs usually secures the closest approach to the ideal. Drug
      combinations used usually include a short-acting properative anxiolytic (e.g.
      midazolam), intravenous propofol (a short-acting potent anxiolytic and amnestic
      agent) for induction of anaesthesia (and sometimes for maintenance) and primary
      maintenance of anaesthesia with inhaled nitrous oxide combined with a poorly
      soluble (low solubility produces rapid recovery; the least soluble is desflurane)
      potent inhaled anaesthetic delivered at a low inflow rate (to minimise cost).
      Although old, nitrous oxide is inexpensive and has favourable pharmacokinetic and
      cardiovascular advantages; however, it is limited in its anaesthetic/amnestic
      potency, and has the capacity to increase nausea. In children, induction of
      anaesthesia is often accomplished with sevoflurane rather than desflurane;
      although sevoflurane is modestly more soluble than desflurane, it is non-pungent
      whereas desflurane is pungent. Moderate- or short-acting opioids (fentanyl is
      popular) or nonsteroidal anti-inflammatory agents (especially ketorolac), or
      local anaesthetics are added to secure analgesia during and after surgery.
      Similarly, when needed, moderate- or short-acting muscle relaxants are selected.
      Before the end of anaesthesia, an intravenous antiemetic may be given. With this
      drug combination, patients usually awaken within minutes after anaesthesia and
      can often move themselves to the vehicle for transport to the recovery unit.
      These combinations of anaesthetics and techniques minimise use of expensive drugs
      while expediting recovery (again minimising cost) with minimal or no compromise
      in the quality of recovery.

PMID- 10947305
TI  - Household income losses associated with ischaemic heart disease for US employees.
AB  - OBJECTIVE: To estimate the cost of lost work days due to ischaemic heart disease
      (IHD), and the cost of this reduced productivity using reduction in household
      income. DESIGN AND SETTING: Using 2 years of nationally representative
      observational data, this study examined the effect on household income of IHD.
      This effect was estimated after accounting for unemployment, days lost to illness
      and other effects of illness on the income of workers aged 18 to 64 years. MAIN
      OUTCOME MEASURES AND RESULTS: Previous measures of indirect costs of disease have
      typically not included the loss in productivity due to suboptimal work
      performance. Among workers in this age group, IHD was associated with a reduction
      of $US3013 in annual household income; this reduction was independent of
      occupational class, age, size of household and educational level. Such a
      reduction may be because of reduced on-the-job performance, employer perception
      of this, or unrelated lifestyle choices. It represents an estimated $US6.05
      billion annual loss in productivity in 1992 dollars (or $US6.45 billion in 1996
      dollars). CONCLUSIONS: Estimates of the indirect costs of chronic disease that do
      not account fully for the lost income of employees may significantly
      underestimate the benefits to employers and society of treatment and prevention.

PMID- 10947304
TI  - The cost effectiveness of misoprostol prophylaxis alongside long-term
      nonsteroidal anti-inflammatory drugs. Implications of the MUCOSA trial.
AB  - OBJECTIVE: This study considered the cost effectiveness of misoprostol
      prophylaxis for nonsteroidal anti-inflammatory drug (NSAID)-induced
      gastrointestinal damage, using data from the Misoprostol Ulcer Complications
      Outcomes Safety Assessment (MUCOSA) trial. The initial aim was to gain listing of
      misoprostol on the Australian National Formulary. DESIGN: The economic evaluation
      followed a 2-stage approach in considering the cost effectiveness of misoprostol,
      a 'within-trial' analysis followed by a simple modelled analysis which explored
      the implications of the trial results for life-years saved beyond the trial
      setting. The perspective of the evaluation is that of the healthcare system.
      SETTING: Three different populations were considered: the total trial population;
      patients with a history of peptic ulcer disease; and patients over 65 years of
      age. STUDY POPULATION: Patient data were taken from the MUCOSA trial, which
      involved 8843 patients receiving continuous NSAID therapy for the control of
      rheumatoid arthritis. INTERVENTIONS: Misoprostol plus any NSAID therapy was
      compared with placebo (no misoprostol) plus any NSAID therapy. MAIN OUTCOME
      MEASURES AND RESULTS: The study found the incremental cost per definite serious
      gastrointestinal complication avoided with misoprostol was 39,603 Australian
      dollars ($A) for the total trial population, $A5599 for patients with a history
      of peptic ulcer disease and $A35,405 for patients over 65 years of age. The
      incremental cost per life-year saved with misoprostol was $A41,866 for the whole
      group, $A6244 for patients with a history of peptic ulcer disease and $A40,322
      for patients over 65 years of age. CONCLUSIONS: The study found misoprostol to be
      cost effective in this setting.

PMID- 10947307
TI  - Scan or scam? If you're thinking of a full-body X ray simply as a health check,
      you'll probably waste your money.

PMID- 10947306
TI  - What's off, what's on. A new list cites 218 things that may cause cancer--and a
      couple that don't.

PMID- 10947308
TI  - The science of women & sex.

PMID- 10947309
TI  - Qualified medical child support orders--California health insurance coverage
      assignment orders--national medical support notices: what's a plan administrator
      to do?
AB  - Many employer-sponsored health plans and multi-employer health benefit trusts
      have seen an increase in medical child support orders (MCSOs), and they can
      anticipate receiving a greater number in the future. Once regulations are final
      for the national medical support notice (NMSN) required by the Child Support
      Performance and Incentive Act of 1998, plans should also begin receiving these.
      In preparation, plan administrators should ensure that they have proper
      procedures in place for determining whether MCSOs and NMSNs constitute QMCSOs.

PMID- 10947310
TI  - Preparing Taft-Hartleys for the 21st century: health care leads list of
      challenges for plan administrators.
AB  - Rising health care costs are a major challenge facing administrators of Taft
      Hartley health and welfare plans. Managing costs while continuing to provide
      coverage that meets members' expectations and needs will require a delicate
      balancing act. Among areas that require close scrutiny are legislative activity,
      retiree medical benefits, prescription drugs, funding and cost-control methods.

PMID- 10947311
TI  - Would-be quitters get help winning against nicotine.

PMID- 10947312
TI  - An introduction to HIV drug resistance testing.

PMID- 10947313
TI  - HIV genotyping by reverse hybridization.

PMID- 10947314
TI  - HIV genotyping by chip technology.

PMID- 10947315
TI  - HIV genotyping by DNA sequencing.

PMID- 10947316
TI  - Therapeutic drug monitoring of antiretroviral agents.
AB  - HIV+ patients fail antiretroviral therapy due to inadequate drug concentrations
      reaching the site of viral replication and/or the development of viral resistance
      to the antiretroviral agents. Adequate drug concentrations may not be reaching
      the virus due to poor compliance, poor absorption, or other pharmacokinetic
      factors such as metabolism, elimination, and drug interactions. The most
      important and most common pharmacokinetic drug interactions involve inhibition of
      metabolism, induction of metabolism, altered drug absorption, inhibition of renal
      excretion, and displacement from plasma protein binding sites. If a patient is
      failing antiretroviral therapy, TDM of antiretroviral agents could help in
      determining both adequacy of drug concentrations and patients' adherence. Ongoing
      studies will determine whether total drug concentration or free drug
      concentration of the protease inhibitors is the best predictor of response.
      Trough concentrations could prove to be the most important predictor of response,
      but additional studies are needed to compare trough, peak, and AUC concentrations
      with response to treatment. Finally, if some patients fail therapy due to
      inadequate drug concentrations, then increasing the dose could benefit patients'
      outcome and increase longevity. Clinical trials are needed that compare patients
      who receive a fixed-dosage regimen with patients who have adjusted dose regimens.
      Such a study is the best way to determine the true value of TDM of the
      antiretrovirals.

PMID- 10947317
TI  - The history of HIV-1 testing.

PMID- 10947318
TI  - Computerized equipment for the delivery of inhaled doses of solid particles in
      specific bronchial challenge.
AB  - An apparatus to generate solid particles was tested for use in diagnosing
      occupational asthma. This equipment measures the inhaled dose of dry particles
      during specific inhalation challenge. It includes an aerosol generator, a cyclone
      type particle size selector, and an inhalation chamber to which a patient
      breathing at tidal volume can be connected for the test. It is fully controlled
      by a standard personal computer in automatic mode, acting on the flow rate and
      the aerosol generator to maintain the concentration at a fixed value, usually 3
      mg/m3. The dose of aerosol delivered to the patient was calculated from the
      aerosol concentration, and the inhaled volume was calculated by integration of
      the corresponding signals. The coefficient of variation for this measurement was
      estimated to be 12%. The mass median aerodynamic diameter (MMAD) of aerosol
      inside the inhalation chamber was measured for three substances: lactose, wheat
      flour, and buckwheat flour. The MMAD of the aerosol inside the chamber was also
      estimated from the particle size distribution of the raw powder. The relative
      difference between the measured MMAD and the calculated value was less than 15%.
      The corresponding relative difference between the measured geometrical SD and the
      calculated value was found to be less than 26%.

PMID- 10947320
TI  - The relationship between particle deposition in the anterior nasal passage and
      nasal passage characteristics.
AB  - The objective of this study was to examine the effects of nasal passage
      characteristics on anterior particle deposition during cyclical breathing. Forty
      healthy, nonsmoking, adult subjects participated in this study. Nasal passage
      characteristics such as nostril length, width, angle, ellipticity, and minimum
      nasal cross-sectional area were measured. The subjects inhaled a polydisperse
      radioactively tagged aerosol (mass median aerodynamic diameter = 5.4 microns,
      geometric standard deviation [GSD] = 1.3) into the nose and exhaled through the
      mouth. The amount of radioactivity in the nose was measured immediately after
      inhalation and thereafter for 54 minutes. At 52.5 minutes, subjects wiped the
      accessible portion of the anterior nose to remove any remaining activity. The
      difference in activity at 52 and 54 minutes was used as a measure of activity
      removed during the nose wipe. Percentage of activity in the nasal passage at 52
      minutes and percentage of activity removed with the nose wipe were considered
      surrogates for particles deposited in the anterior nasal passage. A multiple
      regression analysis showed that the degree of ellipticity of the nostrils was
      significantly related to particle deposition in the anterior nasal passage. These
      results suggest that ellipticity of the nostrils may be a determinant of the
      amount of particle deposition in the anterior nasal passage.

PMID- 10947319
TI  - Basis for nebulized antibiotics: droplet characterization and in vitro
      antimicrobial activity versus Staphylococcus aureus, Escherichia coli, and
      Pseudomonas aeruginosa.
AB  - The aims of this study were to (1) quantify the particle size characteristics of
      several antibiotics considered suitable for aerosol therapy after aerosolization
      with the PARI IS/2 nebulizer (Pari GmbH, Sarnberg, Germany) and (2) determine the
      degree to which in vitro antimicrobial activity of these antibiotics is
      maintained after nebulization. The aerosolized drugs were tobramycin sulfate,
      streptomycin, and imipenem, with saline solution as the control. Mean mass
      aerodynamic diameter of the nebulized drugs was 3.25 microns for tobramycin, 2.26
      microns for imipenem, and 2.38 microns for streptomycin. In vitro tests showed
      that tobramycin and imipenem were unaltered in their bacteriostatic activity
      against strains of Escherichia coli (American Type Culture Collection [ATCC]
      25922) and Staphylococcus aureus (ATCC 29213) as well as against Pseudomonas
      aeruginosa (ATCC 27853) with minimal inhibitory concentration (MIC) values less
      than 0.3 microgram/mL. Nebulized streptomycin showed significantly higher MIC
      values against P. aeruginosa (ATCC 27853). These results suggest that tobramycin
      and imipenem may be prescribed as an aerosol generated by jet nebulization (PARI
      IS/2) to treat S. aureus, E. coli, and P. aeruginosa infections without any risk
      of altering the drugs minimum bacteriostatic activity by the nebulization
      process. Aerosolization of streptomycin with this nebulizer may not be as
      effective against P. aeruginosa because it seems to alter the bacteriostatic
      activity.

PMID- 10947321
TI  - Effectiveness and acceptability of a domiciliary multidrug inhalation treatment
      in elderly patients with chronic airflow obstruction: metered dose inhaler versus
      jet nebulizer.
AB  - The aim of this study was to compare the immediate and long-term bronchodilator
      effect as well as the patient acceptability of a 2-week, multidrug, inhalation
      treatment delivered by a metered dose inhaler (MDI) versus a jet nebulizer in a
      group of elderly patients with chronic obstructive pulmonary disease (COPD) or
      asthma and an at least partially reversible airflow obstruction. Twenty elderly
      outpatients (17 men; mean +/- SD age, 67 +/- 2 years; mean +/- SD baseline forced
      expiratory volume in 1 second [FEV1], 46.5 +/- 14% of predicted value) with COPD
      or asthma participated in the study, which was of an open, randomized, crossover
      design. After a 1-day baseline evaluation, including patient history, clinical
      examination, and spirometry, participants were randomly assigned to receive a
      multidrug inhalation treatment (a combination of salbutamol, ipratropium, and
      flunisolide) with either an MDI or a jet nebulizer. Two weeks later, they were
      shifted to treatment with the alternative system for a further 2 weeks. FEV1 was
      measured on the first and fourteenth days of each treatment period, on each
      occasion both before and 30 minutes after the morning inhalation. At the end of
      the study, patients were asked to express a personal preference for one of the
      two inhalation treatments with regard to effectiveness and acceptability by
      filling out a simple questionnaire. Both the MDI and jet nebulizer had a
      significant immediate bronchodilator effect on the first and fourteenth days of
      treatment, with no differences between treatments. No long-term bronchodilator
      effect was seen with either aerosol delivery system. Patient preferences were
      clearly in favor of the jet nebulizer with regard to effectiveness and in favor
      of the MDI with regard to acceptability. In conclusion, in elderly patients with
      COPD or asthma and partially reversible airflow obstruction, a maintenance
      multidrug bronchodilator/anti-inflammatory inhalation treatment produced a
      statistically significant and clinically relevant bronchodilator effect without
      substantial differences between the two delivery systems. Most patients
      considered the MDI to be more acceptable and the jet nebulizer to be more
      effective. These preferences should be taken into consideration when prescribing
      a maintenance aerosol inhalation treatment.

PMID- 10947322
TI  - Treating asthma in children with beclomethasone dipropionate: Pulvinal versus
      Diskhaler.
AB  - Seventy-two children (mean age, 10.1 years) with stable moderate asthma who
      completed a 7-day run-in period were randomized to receive a 4-week treatment
      with beclomethasone dipropionate (200 micrograms twice daily) administered
      through two different powder inhalers (Pulvinal; Chiesi Farmaceutici S.p.A,
      Parma, Italy and Diskhaler; Glaxo-Wellcome, Evreux, France) in a parallel group
      design. Sixty-nine patients completed the study. Morning and evening peak
      expiratory flow values, the use of rescue salbutamol, and the severity of
      clinical symptoms were recorded daily on a diary card. Pulmonary function tests
      were performed at baseline and then after 2 and 4 weeks of treatment. Pulmonary
      function values, daily morning and evening peak expiratory flow, and most of the
      clinical symptoms significantly improved, although the use of rescue salbutamol
      significantly decreased from the second week of treatment until the end of the
      study in both groups. Equivalence of efficacy between groups was demonstrated for
      both pulmonary function and clinical parameters. We conclude that the Pulvinal
      inhaler is as efficacious as the Diskhaler in beclomethasone-based therapy of
      asthmatic children.

PMID- 10947323
TI  - Retention of Teflon particles in hamster lungs: a stereological study.
AB  - The significance of aerosols in medicine is increased when the distribution of
      inhaled aerosols in the different respiratory tract compartments and their
      interaction with lung structures are known. The aim of this study was to
      investigate the retention of the hydrophobic Teflon spheres used in human beings
      so as to analyze their regional distribution and to study their interaction with
      lung structures at the deposition site. Six intubated and anesthetized Syrian
      Golden hamsters inhaled aerosols of Teflon particles with an aerodynamic diameter
      of 5.5 microns by continuous negative-pressure ventilation adjusted to slow
      breathing. Lungs were fixed by intravascular perfusion within 21 minutes after
      inhalation was started, and tissue samples were taken and processed for light and
      electron microscopy. The stereological (fractionator) analysis revealed that
      particle retention was the greatest in alveoli (72.4%), less in intrapulmonary
      conducting airways (22.9%), and the least in extrapulmonary mainstem bronchi
      (0.3%) and trachea (4.4%). Particles were found submerged in the aqueous lining
      layer and in close vicinity to epithelial cells. In intrapulmonary conducting
      airways, 21.5% of Teflon particles had been phagocytized by macrophages. This
      study with highly hydrophobic Teflon particles clearly demonstrates that for
      spheres of this size, surface tension and line tension forces rather than the
      particles' surface free energy are decisive for the displacement of particles
      into the aqueous phase by surfactant. It was this displacement that enabled
      subsequent interaction with macrophages. Refined knowledge of particle retention
      may help us to better understand the biological response to inhaled particles.

PMID- 10947324
TI  - The Aerosol Society Drug Delivery to the Lungs X. London, United Kingdom,
      December 2-3, 1999. Abstracts.

PMID- 10947325
TI  - A potential method for the specification of microbial barrier properties.
AB  - A microbial barrier test to determine the barrier characteristics of porous
      packaging materials has been developed that will allow real-time testing in
      manufacturing environments. None of the barrier challenge tests used to date have
      achieved universal acceptance and they have taken days to perform. The new
      physical test means that quality control can be conducted on the manufacturing
      line in 10 minutes. The findings of tests conducted on porous barrier materials
      are reported.

PMID- 10947326
TI  - Microsystems: small structures, big impact.
AB  - Microsystems are devices that incorporate a combination of microfluidic,
      micromechanical, microoptical and microelectronic components. This is the first
      in a series of articles looking at the major impact the technology is likely to
      have on medical products during the next 10 years and how companies can profit
      from the opportunities it offers.

PMID- 10947327
TI  - Design comment: bluetooth.

PMID- 10947328
TI  - Packaging and the environment: a regulation update.
AB  - This article reports on the progress that is being made on standards and
      associated documents to support the Packaging and Packaging Waste Directive.
      Potential revisions are also discussed.

PMID- 10947329
TI  - Medical device reporting: another final rule, Part II.
AB  - Part I of this article discussed the chronology of the United States (US) Medical
      Device Reporting (MDR) regulations, the suspension of the US Designated Agent
      requirements, and important considerations concerning reporting responsibilities
      for non-US manufacturers. This article will discuss the contents of the recently
      published MDR final rule.

PMID- 10947330
TI  - Towards global in vitro diagnostic standards, Part I.
AB  - The first global harmonized standards for in vitro diagnostic products (IVD) are
      nearing completion. The ISO Technical Committee overseeing this work will meet in
      June 2000 to prepare for the final vote. Six of these standards are mandated for
      the IVD Directive. This two-part report on the current status of these standards
      provides an insight into the international standardization process and suggests
      ways that industry can make it work more effectively.

PMID- 10947331
TI  - New routes to the United States: special and abbreviated 510(k)s.
AB  - Special and Abbreviated 510(k)s are two new approaches to obtaining clearance for
      medical devices to be marketed in the United States (US) that are designed to
      streamline the traditional 510(k) review process. This article answers commonly
      asked questions relating to the requirements for these types of 510(k)s,
      preparation of applications, and how the US Food and Drug Administration handles
      these submissions.

PMID- 10947332
TI  - Ireland's winning formula. Interview with Noel Treacy, T.D., Ireland's Minister
      for Science and Technology.

PMID- 10947333
TI  - The Italian medical equipment market.

PMID- 10947334
TI  - Adhesive and nonadhesive systems for health-care packaging.
AB  - This review of the important attributes of adhesive systems also assesses the
      potential benefits of nonadhesive systems, such as peelable films, which are
      gaining favour as cost-saving alternatives.

PMID- 10947335
TI  - Diagnosis related group costs in a regulated environment. A note about their
      economic interpretation.
AB  - The availability of the Diagnosis Related Group (DRG) system for determining
      hospital costs in some European countries has encouraged its use in
      pharmacoeconomic evaluations. The DRG system was developed in the US to provide
      data for prospective payments for hospitals. However, the financing of hospitals
      in some European countries is still based on the so-called 'global budget'
      approach. Therefore, results of pharmacoeconomic studies involving hospitals
      financed by the 'global-budget' approach in which DRG costs have been used
      require careful consideration. The main points to consider are: (i) that most of
      the cost components constituting the DRGs are in fact charges fixed by the
      government. This cost-charge ratio varies significantly across different DRGs,
      altering economic consequences when cost-shifting between DRGs; (ii) that there
      is rarely a perfect concordance between attributable cost (as proposed by the
      DRGs) and the definition of variable cost (as defined in economic evaluations);
      (iii) from the Sickness Fund's point of view, the way DRGs could be interpreted
      is rather unclear: financing or bench-marking?; and (iv) the perspective of DRG
      cost is a mixed patient-hospital perspective which is neither the societal nor
      the health insurance perspective generally used in pharmacoeconomic evaluations.
      In conclusion, the use of DRG costs is a major improvement for pharmacoeconomic
      evaluation. However, many hypotheses still need to be made in these studies,
      depending on the economic perspective of the study. Therefore, the results of
      pharmacoeconomic studies should be considered and discussed in line with the
      national financing system of the hospitals involved.

PMID- 10947336
TI  - New generation aromatase inhibitors in breast cancer. Weighing out potential
      costs and benefits.
AB  - Endocrine therapy is the oldest and still one of the most effective forms of
      systemic therapy for breast cancer. Unfortunately, only one-third of all breast
      carcinomas respond to a strategy that modifies the activity of estrogen at the
      level of the tumour. Therefore, it is important that patients with cancer likely
      to respond are reliably identified. Substantial evidence indicates that tumour
      estrogen receptor level is the best predictor of response to hormonal therapy.
      Although antiestrogen therapy is still considered the endocrine modality of
      choice for all stages of breast cancer, there is renewed interest in finding new
      agents with improved therapeutic indices. The development of agents which
      selectively suppress aromatase, a key enzyme in estrogen biosynthesis, can be
      attributed not only to the importance of extraglandular aromatase activity, but
      also to the unparalleled success of tamoxifen. The present status, emerging roles
      and concerns of the new aromatase inhibitors are discussed in order to assess
      their potential costs and therapeutic merit.

PMID- 10947338
TI  - Valuing health-related quality of life. A review of health state valuation
      techniques.
AB  - Given the growing need to value health-related quality of life, a review of the
      literature relating to health state valuation techniques was undertaken to
      appraise the current theoretical and empirical evidence available to inform on
      the techniques, to identify consensus, identify disagreement and identify
      important areas for future research. A systematic search of the literature was
      conducted, covering standard gamble (SG), time trade-off (TTO), visual analogue
      scale (VAS), magnitude estimation (ME) and person trade-off (PTO) techniques. The
      basic concepts of practicality, reliability, theoretical validity and empirical
      validity formed the criteria for reviewing the performance of valuation
      techniques. In terms of practicality and reliability, we found little evidence
      relating to ME and PTO. SG, TTO and VAS have been shown to be practical on a
      range of populations. There is little difference between the reliability of SG,
      TTO and VAS, and present evidence does not offer a basis to differentiate between
      them. When considering the theoretical basis of techniques, we conclude that
      choice-based methods (i.e. SG, TTO and PTO) are best placed to reflect the
      strength of preference for health, with the choice between these techniques
      depending on the study characteristics and the perspective employed. Empirical
      evidence relating to the theoretical perspective of the techniques has shown that
      there are problems with all techniques in terms of descriptive validity.

PMID- 10947337
TI  - Pharmacoeconomic considerations in treating ovarian cancer.
AB  - Ovarian cancer is the leading cause of death in women with gynaecological
      cancers. The most common type of ovarian cancer is epithelial ovarian cancer.
      Referred to as the 'silent' killer, this disease is difficult to detect because
      of the lack of specific symptoms. The majority of women who have ovarian cancer
      are diagnosed in the advanced stages. While the exact cause of ovarian cancer
      remains elusive, it is believed that the events relating to incessant ovulatory
      function play a major role in the development of this disease. Long term
      prognosis of women with ovarian cancer remains grim. Although ovarian cancer is
      highly responsive to chemotherapy, most women will develop persistent or
      recurrent disease after primary treatment. The standard front-line treatment is
      paclitaxel in combination with a platinum-based agent; however, toxicities
      associated with paclitaxel must be weighed against the clinical benefit. The
      economic issues associated with the treatment of ovarian cancer involve costs of
      chemotherapy agents and management of supportive care. Patient preferences and
      quality-of-life issues are also of major importance because of the short survival
      benefit for most patients. Therefore, quality of life must be maximised alongside
      efforts to prolong survival. More research is necessary to determine what trade
      offs (e.g. adverse effects of treatment) patients are willing to make for modest
      gains in survival.

PMID- 10947339
TI  - The costs of pharmacological treatment for major depression. The Italian
      Prospective Multicentre Observational Incidence-Based Study.
AB  - OBJECTIVE: To describe the pharmacological treatment for major depression under
      the conditions of routine Italian public mental health facilities, assess its
      costs, and study its main predictors according to a societal perspective. DESIGN:
      This was a prospective multicentre observational study designed to evaluate the
      economics of treatment of major depression using a specifically designed 65-item
      questionnaire. Data on drug consumption were collected in a section of the
      questionnaire and are presented here. PATIENTS AND PARTICIPANTS: 60 mental health
      facilities were selected and 556 patients were enrolled and followed up for 15
      months. RESULTS: Pharmacological treatment appears to be the most common
      treatment for major depression. 98% of patients were prescribed an
      antidepressant. Selective serotonin reuptake inhibitors (SSRIs) were the most
      prescribed antidepressants. Patients treated with SSRIs suffered from less severe
      depression than those treated with tricyclic antidepressants. Benzodiazepines
      were prescribed for 84% of patients enrolled. The total drug cost was 1,120,000
      Italian lire ($US707) per patient (1995 values). Less than 20% of this cost was
      borne by the Italian National Health Service, as the majority of drugs used were
      not reimbursed. CONCLUSIONS: The costs of the most widespread approach to
      treating major depression (pharmacological treatment) are not currently covered
      by the Italian National Health Service. Prescribing of drugs seems to diverge
      from the standards of treatment indicated by the Italian Drug Committee.

PMID- 10947340
TI  - Pharmacoeconomics and clinical practice guidelines. A survey of attitudes in
      Swedish formulary committees.
AB  - BACKGROUND: Swedish formulary committees are expected to influence prescribing
      practice by establishing and issuing drug lists and clinical practice guidelines,
      particularly now that financial responsibility for prescription drugs has been
      transferred from the national to the county council level. OBJECTIVE: The purpose
      of this exploratory study was to identify the information sources and decision
      criteria that individual committee members perceive as important in establishing
      clinical practice guidelines. Moreover, obstacles to the increased use of
      pharmacoeconomic evaluations in decision-making were also identified. DESIGN AND
      SETTING: Data were gathered through a survey questionnaire administered in 1998
      to members of central formulary committees throughout Sweden, as determined by a
      national register. PARTICIPANTS: 312 members of central formulary committees, of
      whom 69% responded. RESULTS: Treatment policies/guidelines supplied by government
      authorities, or found in reviewed journals, are considered the most important
      sources of information, and criteria associated with costs and effects are
      considered the most important decision criteria. The members' years of experience
      and their professions affect their assessments of information sources, whereas
      education in health economics affects their assessments of decision criteria.
      Committee members voiced an interest in pharmacoeconomic issues, but warned that
      there was neither sufficient competence among committee members nor an adequate
      supply of relevant studies. Furthermore, a majority of the members identified
      difficulty in translating study results into clinical practice guidelines and
      limited possibilities in comparing studies as obstacles to the increased use of
      pharmacoeconomic evaluations. CONCLUSIONS: The results of this survey may be
      useful in designing future economic evaluations and when presenting and diffusing
      study results.

PMID- 10947341
TI  - Impact of zanamivir treatment on productivity, health status and healthcare
      resource use in patients with influenza. Zanamivir Study Group.
AB  - OBJECTIVE: This study examined the impact of zanamivir treatment on patient
      morbidity in patients with influenza. DESIGN AND SETTING: This was a multicentre,
      randomised, double-blind, parallel-group study conducted in 14 countries in
      Europe and North America during the winter of 1995/1996. PATIENTS AND
      PARTICIPANTS: The study included 722 individuals with virologically confirmed
      influenza. INTERVENTIONS: Two different zanamivir treatment regimens [twice daily
      (bid) or 4 times daily (qid) for 5 days] were compared with placebo. MAIN OUTCOME
      MEASURES AND RESULTS: Efficacy was measured using a number of patient-assessment
      questionnaires. Results showed that significantly fewer patients with influenza
      who were treated with zanamivir had additional contacts with healthcare
      professionals compared with those who received placebo (8 vs 14%; p < or = 0.049,
      bid and qid vs placebo). Individuals treated with zanamivir also spent fewer days
      absent from work (placebo: mean = 3.28 days; qid: mean = 2.52 days; p = 0.031) or
      college/school (placebo: mean = 2.90 days; bid: mean = 2.24 days; p = 0.032), and
      showed significant improvements in productivity compared with placebo. The health
      status questionnaire revealed significant improvements in patient well-being over
      the first 5 days of the study in those treated with zanamivir compared with those
      who received placebo. CONCLUSIONS: Zanamivir treatment reduced absenteeism,
      improved patient productivity and well-being, and reduced the additional use of
      healthcare resources in patients with influenza.

PMID- 10947342
TI  - Cost-of-illness of epilepsy in Italy. Data from a multicentre observational study
      (Episcreen).
AB  - OBJECTIVE: To investigate the impact of epilepsy in Italy on healthcare
      resources, producing an average cost per patient per year of follow-up. DESIGN
      AND SETTING: The Episcreen Project is a multicentre longitudinal Italian
      observational study; its methodology, organisational network and case report form
      have been reported in detail elsewhere. Using a subset of patients with epilepsy
      from this project, we conducted a retrospective cost-of-illness analysis based on
      clinical records. The analysis was performed from the societal (community)
      perspective, including both direct and indirect costs. Hospital admissions, day
      hospital visits, specialist visits, instrumental examinations, drugs and
      productivity losses because of visits and hospitalisation were analysed. Each
      cost variable was valued in 1996 Italian liras (L) using published national
      tariffs (except for drugs for which published prices were used). A sensitivity
      analysis was conducted on indirect costs to test the robustness of the assumption
      that 1 working day lost for each day hospital visit would produce a change of
      0.3% in the weight of indirect costs. PATIENTS AND PARTICIPANTS: Patients
      analysed in this study were registered in the Episcreen database as at 21
      November 1996. They were diagnosed with epilepsy at the last visit, had at least
      1 follow-up visit (i.e. at least 1 visit after the enrolment visit), and had at
      least 12 months of follow-up. RESULTS: The average cost per patient per year was
      L2,726,116 ($US1767). The average cost per patient was higher for children than
      for adults [L3,629,997 ($US2353) and L2,362,134 ($US1531), respectively), and for
      newly diagnosed patients for whom the first diagnosis of epilepsy was addressed
      at the first Episcreen visit [adults: old referrals L1,304,353 ($US845), new
      referrals L6,901,374 ($US4473); children: old referrals L2,810,504 ($US1822), new
      referrals L7,814,400 ($US5065)]. Direct costs represented 87.6% of total costs.
      The major cost driver was hospitalisation (63.7%), followed by drugs (10.5%), day
      hospital visits (4.1%), out-patient visits (3.85%), other tests (3.1%) and
      electroencephalographs (2.3%). Indirect costs (lost productivity) represented
      12.4% of total costs. Sensitivity analysis showed that the results are sensitive
      to the value attributed to lost productivity. CONCLUSIONS: The cost of managing a
      patient with epilepsy in Italy is influenced by age, syndrome and modality of
      referral to the centre for epilepsy.

PMID- 10947344
TI  - The revolution has begun.

PMID- 10947343
TI  - Economic analysis of long-term reversible contraceptives. Focus on Implanon.
AB  - OBJECTIVE: To examine the economic impact of a new implantable contraceptive,
      Implanon, in comparison with other available contraceptive methods. DESIGN: This
      was a modelling study using cost data derived from national published sources and
      effectiveness data from either controlled clinical trials (Implanon) or reports
      in the literature (other contraceptives). In the baseline analysis, Implanon was
      compared with 2 long term reversible contraceptives, Norplant and Mirena. Further
      analyses were then carried out comparing Implanon with Depo-Provera and with
      combined oral contraceptives. SETTING: The study concentrated on the UK, but also
      made reference to several other European countries. MAIN OUTCOME MEASURES AND
      RESULTS: The baseline analysis showed that all 3 long term reversible
      contraceptives produce very good rates of return, with Implanon providing the
      best rate of return (both average and internal) of the 3 methods. The payback
      period for Implanon was calculated as 146 days, compared with 339 and 368 days
      for Norplant and Mirena, respectively. In terms of cost effectiveness, the cost
      per protected year for Implanon was 95 Pounds, compared with 146 Pounds and 168
      Pounds for Norplant and Mirena, respectively. In comparison with Depo-Provera (an
      injectable contraceptive), Implanon was both less costly and more effective, the
      cost per protected year for Depo-Provera being 131 Pounds. The threshold beyond
      which Implanon delivers cost savings compared with combined oral contraceptives
      was at a failure rate of 4.9% for the combined pill. CONCLUSIONS: Reversible long
      term approaches to contraception provide an effective and efficient use of
      healthcare resources and generate an excellent return on public investment.
      Implanon produces better rates of return than both Norplant and Mirena, and is
      also more cost effective in terms of cost per pregnancy avoided and cost per
      protected year than Norplant, Mirena, Depo-Provera and oral contraceptives.

PMID- 10947345
TI  - Building for tomorrow: the idealized design of clinical office practices.

PMID- 10947346
TI  - Strategies for expanding your patient base in diverse communities.

PMID- 10947347
TI  - Off the charts: teaching students in compliance with HCFA guidelines.

PMID- 10947348
TI  - As good as it could get: remaking the medical practice.

PMID- 10947349
TI  - Understanding the risks of medical interventions.

PMID- 10947350
TI  - The field of health communication today: an up-to-date report.
AB  - One important starting point for the field of health communication was the
      Stanford Heart Disease Prevention Program, a multiyear community intervention
      that began 25 years ago. Health communication is a specialty field of
      communication study that includes the media agenda-setting process for health
      issues; media advocacy for health; scientific communication among biomedical
      scientists; doctor-patient communication; and, particularly, the design and
      evaluation of preventive health communication campaigns, the focus of this
      article. Health communication study today is a well-established, expanding
      specialty in the United States and abroad.

PMID- 10947351
TI  - The status and scope of health communication.
AB  - We examine the field of health communication with a multimethodological analysis,
      presenting a brief historical synopsis of the academic literature as well as the
      results of a survey administered to academicians who identified communication and
      health to be major fields of interest. After this descriptive backdrop of health
      communication, we offer a prescription for an ideal health communicator--that is,
      one with an interdisciplinary background--to use ethical, persuasive means to
      craft, deliver, and evaluate campaigns that promote good health and disease
      prevention; to plan, influence, and implement health policy; and to employ
      ethical decision making that will enhance the quality of life for individuals and
      communities throughout the globe.

PMID- 10947352
TI  - Health communication: making the most of new media technologies--an international
      overview.
AB  - Not since the hundred years following Gutenberg's invention of the printing press
      in c. 1450 has there been such a tidal wave of change in the way humans
      communicate. We are moving from the Age of Mass Communication into the Age of
      Interactive Communication, in which many of the old communication models will be
      insufficient or redundant. The rate of diffusion of these new media technologies
      almost defies comprehension. The convergence of computer, telecommunication, and
      televisual technologies is presenting the consumer with a myriad of choices. The
      challenge for the communicator is to find a way through this maze and to ensure
      that the message is received. For the health communication professional, the
      urgency of the message often adds further difficulty to the task. Differing rates
      of diffusion internationally and a confusion of technologies do not make the
      problem any easier.

PMID- 10947353
TI  - The status of clinic-based STD patient education: the need for a commitment to
      innovation in health communication.
AB  - Although knowledge of safer sex practices is increasing in high-risk populations,
      such as STD clinic patients, this knowledge does not often translate into
      behavior change. As a result, STD reinfection rates among clinic patients remain
      high, resulting in large numbers of return patient visits. As part of a study to
      evaluate strategies for improving clinic-based education for patients with STDs,
      we conducted formative research interviews with inner-city clinic managers or
      other key staff to identify opportunities for and barriers to enhancing STD
      patient education. These interviews revealed that most of the inner-city clinics
      had not introduced any new or innovative health communication strategies in the
      last several years. A primary barrier to innovation appeared to be the belief
      that patient needs were sufficiently addressed through one-on-one counseling, an
      assumption that does not take into account the limitations of this form of
      provider-patient communication. Another barrier was the emphasis placed on
      maintaining clinic flow, with little consideration given to how it might be
      altered to accommodate new educational approaches. We offer recommendations to
      encourage STD clinics to experiment with new and potentially more powerful health
      communication methods and to encourage the CDC and other funders to alter their
      STD service priorities toward improvements in health communication and education.
      We also offer steps that health communication specialists can take in helping
      clinics and funders move toward these goals.

PMID- 10947354
TI  - Advances in segmentation modeling for health communication and social marketing
      campaigns.
AB  - Large-scale communication campaigns for health promotion and disease prevention
      involve analysis of audience demographic and psychographic factors for effective
      message targeting. A variety of segmentation modeling techniques, including tree
      based methods such as Chi-squared Automatic Interaction Detection and logistic
      regression, are used to identify meaningful target groups within a large sample
      or population (N = 750-1,000+). Such groups are based on statistically
      significant combinations of factors (e.g., gender, marital status, and
      personality predispositions). The identification of groups or clusters
      facilitates message design in order to address the particular needs, attention
      patterns, and concerns of audience members within each group. We review current
      segmentation techniques, their contributions to conceptual development, and cost
      effective decision making. Examples from a major study in which these strategies
      were used are provided from the Texas Women, Infants and Children Program's
      Comprehensive Social Marketing Program.

PMID- 10947355
TI  - Health legacies from Franklin Roosevelt to Robert Dole, or how medical and health
      care issues took over the nation's news.
AB  - Coverage of medical and health care issues has become a staple of the American
      press. To explain today's saturation of such coverage, I present a political
      continuum from reporting on the health of President Franklin Roosevelt to that of
      Republican presidential candidate Robert Dole. I suggest that the public can
      better be served by disclosures of medical records of political candidates as
      well as of elected officials.

PMID- 10947356
TI  - Communicating to promote justice in the modern health care system.
AB  - The systemic prejudices and biases that often limit the effectiveness of health
      care delivery are examined. How the inherent imbalance in control between
      consumers and providers of health care, based on the micropolitics of sharing
      relevant health information, perpetuates a system of marginalization and
      alienation within health care delivery systems is discussed. Communication
      barriers that often confront many stigmatized groups of health care consumers,
      such as the poor, people with AIDS, minorities, the ill elderly, and women, are
      identified. Such prejudicial treatment is framed within a cultural ideologies
      model, leading to identification of communication strategies for promoting
      justice in the modern health care system and enhancing the quality of health care
      delivery.

PMID- 10947357
TI  - AIDS knowledge gaps: results from the first decade of the epidemic and
      implications for future public information efforts.
AB  - Throughout the first decade of AIDS, certain populations have been
      disproportionately affected by its spread, particularly men, blacks, Hispanics,
      and the young. Just as there are population differences in the spread of the
      disease, there are differences in knowledge about the disease as well. This
      article applies the knowledge gap framework to examine the nature and magnitude
      of gaps in knowledge among different populations. The analysis shows that persons
      of low education lag behind other groups in true-transmission knowledge (i.e.,
      knowledge about ways in which HIV/AIDS actually is transmitted) and false
      transmission knowledge (i.e., misconceptions about how the disease is spread).

PMID- 10947358
TI  - Confronting cancer on thirtysomething: audience response to health content on
      entertainment television.
AB  - This study addresses the potential of entertainment television to educate about
      serious subject matter, such as health content. Through the use of open-ended, in
      depth interviews of regular viewers in two metropolitan sites, this study
      explores audience response to a fictionalized, serialized portrayal of ovarian
      cancer on thirtysomething. Our questions were directed to the audience's (a)
      viewing process, including interpersonal contact, identification with characters,
      and prior experience with cancer, (b) understanding of content, especially
      illness imagery and coping strategies, and (c) applications to real life,
      including questions, insights, knowledge, and actions. The details of this
      exploration indicate the complexity of audience response to this kind of content
      and suggest guidelines for health communicators as they work with the
      entertainment industry to embed health-promoting messages in the media.

PMID- 10947359
TI  - Advancing public health goals through the mass media.

PMID- 10947360
TI  - Recommendations to improve health risk communication: lessons learned from the
      U.S. Public Health Service.
AB  - The growth in the public's concern over a variety of environmental health risks
      has placed new requirements and demands on U.S. Public Health Service (PHS)
      agencies for information that describes and explains the nature of risk in clear
      and comprehensible terms. Experience has shown, however, that merely
      disseminating information without reliance on communication principles can lead
      to ineffective health messages and public health actions. This article presents
      the findings of a study conducted by the Subcommittee on Risk Communication and
      Education of the Environmental Health Policy Committee (EHPC), PHS, on how PHS
      agencies are communicating information about health risk; how effective these
      communications have been; and what specific principles, strategies, and practices
      best promote effective health risk communication. The purpose of the
      Subcommittee's study was to develop specific recommendations that would help PHS
      decision makers and health risk communicators improve the effectiveness of health
      information provided to, and received from, the public. The study suggests
      fundamental principles drawn from a series of case studies from PHS agencies
      about how best to plan and carry out risk communication activities.

PMID- 10947361
TI  - Notes from the field: does publishing in academic journals make a difference?

PMID- 10947362
TI  - Does research have any role in information/education/communication programs in
      Africa? An insider's view.

PMID- 10947364
TI  - Theory and method in health audience segmentation.
AB  - Audience segmentation is widely regarded as essential to effective health
      communication campaign efforts. Nonetheless, its practice is typically ad hoc.
      The conceptual history and theoretical bases for audience segmentation are
      reviewed, and typical audience segmentation strategies for health communication
      efforts are described and critiqued. An analogy is drawn between the
      methodological problems associated with audience segmentation and those of
      multivariate classification and taxonomy in botany and zoology. Cluster analytic
      techniques responsive to these issues are described, as are applications of these
      techniques for analysis of health communication campaign audiences. Approaches
      that would permit widespread use of such segmentation strategies are discussed,
      and recommendations for such efforts are made.

PMID- 10947363
TI  - Mass-media-generated interpersonal communication as sources of information about
      family planning.
AB  - This study suggests that mass-media-generated interpersonal communication
      networks vary according to an individual's behavior-change stage. As people in
      Peru adopted modern family planning methods, they increasingly formed and perhaps
      relied on information from more technical interpersonal communication networks,
      which shifted from peers to doctors and other service providers. Moreover,
      information seeking and giving varied with adoption stages in unexpected ways. In
      collaboration with Apoyo a Programmas de Poblacion (Advocacy for Population
      Programs) of Peru, we present a model of how interpersonal communication networks
      generated by mass media messages vary with stage of behavior change.

PMID- 10947365
TI  - Evaluating health knowledge: an alternative approach.
AB  - Health campaigns concerned with HIV and AIDS confront two important barriers: the
      stigmatized nature of the disease and cultural values that exacerbate the taboo
      nature of the information disseminated. The use of surveys in HIV and AIDS
      research requires respondents to provide descriptions of sexual acts and body
      parts as measures of their knowledge. Focus groups and interviews require
      respondents to speak publicly about these topics. Although many young people know
      about HIV and AIDS, they may not have the vocabulary to express their complete
      knowledge either textually or verbally. This article describes an alternative
      approach designed to evaluate HIV and AIDS knowledge among 587 adolescents in
      Mexico, where the number of official cases of AIDS has increased steadily since
      1981. Participants stratified on sex and social class were required to draw modes
      of HIV transmission. The drawings were categorized into drawings of objects and
      persons, focusing on behaviors or cognitions, with a relational or contextual
      emphasis. The utility of this method for measuring knowledge about HIV infection
      and AIDS in education campaigns and evaluation research is discussed.

PMID- 10947366
TI  - Economic, ethical, and outcome-based decisions regarding aggressive surgical
      management in patients with penetrating craniocerebral injury.
AB  - Each year fatalities in the United States increase as a result of gunshot wounds
      to the head. This increase, coupled with the progressive limitation of medical
      and economic resources available at major trauma centers, has brought into
      question the concept that everything possible should be done to save the lives of
      victims, who have only a minimal and nonpredictable chance of having a good
      outcome. Thus, consideration must be given to the economics of treating cranial
      gunshot wounds and the relationship of this treatment to outcome. When a good
      outcome can be predicted, treatment should be aggressive. However, when a good
      outcome cannot be predicted, surgical intervention will have no effect and the
      potential costs of aggressive treatment must also be considered. Clearly, there
      are ethical dilemmas involved in withholding operative treatment from any
      individual, even if there is only a minimal chance of a reasonable neurologic
      recovery. A negotiation-based approach should be used in determining the medical
      and ethical benefits of aggressive management strategies. Unfortunately, the care
      of critically ill patients is inconsistent with this approach. In order to insure
      that the best decision is made, guidelines dictating when to surgically intervene
      must be made an essential part of the patient/health care provider negotiation-
      even in worst case scenarios. The combination of an extremely poor prognosis for
      these injuries, and economic constraints faced by government-run facilities today
      could suggest that some patients should be allowed to die. Thus, the physician
      must be a source of information for the families, providing support and becoming
      a decision-making partner regarding potential intervention. In each situation, a
      strict set of guidelines must be formulated to establish a moral foundation for
      the ultimate mutual decision.

PMID- 10947367
TI  - Predicting risk behaviors: development and validation of a diagnostic scale.
AB  - The goal of this study was to develop and validate the Risk Behavior Diagnosis
      (RBD) Scale for use by health care providers and practitioners interested in
      promoting healthy behaviors. Theoretically guided by the Extended Parallel
      Process Model (EPPM; a fear appeal theory), the RBD scale was designed to work in
      conjunction with an easy-to-use formula to determine which types of health risk
      messages would be most appropriate for a given individual or audience. Because
      some health risk messages promote behavior change and others backfire, this type
      of scale offers guidance to practitioners on how to develop the best persuasive
      message possible to motivate healthy behaviors. The results of the study
      demonstrate the RBD scale to have a high degree of content, construct, and
      predictive validity. Specific examples and practical suggestions are offered to
      facilitate use of the scale for health practitioners.

PMID- 10947368
TI  - Social marketing and diffusion-based strategies for communicating with unique
      populations: HIV prevention in San Francisco.
AB  - We conducted a 2-year investigation of the extent to which strategies based on
      social marketing and diffusion of innovations concepts are used in preventive
      health communication with unique (highly ostracized) populations. Of the 49
      organizations in San Francisco that operate HIV prevention programs (N = 100),
      programs that most highly targeted unique populations were surveyed. Personal
      interviews were then conducted with 38 staff leaders who operated the most and
      least effective programs. Audiotapes and transcripts were content analyzed to
      identify the strategies used by program staff. Strategies based on social
      marketing concepts were more prevalent than strategies based on the diffusion of
      innovations: More effective programs were characterized by emphasis on homophily,
      audience segmentation, compatibility-based strategies, and interorganizational
      collaboration.

PMID- 10947369
TI  - Values and justifications in health communication interventions: an analytic
      framework.
AB  - A conceptual framework for analyzing health communication interventions is
      presented as a systematic approach to identify values and justifications embedded
      in major facets of the communication intervention: the definition of the problem,
      the strategies adopted, the intervention stakeholders or its targeted
      populations, and the evaluation of the program. Although values and ethical
      concerns are embedded in all facets of health communication interventions, they
      are often left unexamined, or are taken for granted by practitioners and
      intervention populations (policy makers and the researchers who analyze,
      evaluate, or help design and implement them). The development, adaptation, and
      application of this framework can serve three inter-related purposes: (1) to
      provide constructs and a systematic approach to examine the design and
      implementation of interventions from a normative perspective, (2) to contribute
      to a theoretical perspective on health interventions as a social change
      phenomenon, and (3) to provide additional criteria for program evaluation and
      policy-making.

PMID- 10947370
TI  - Tobacco: coopting our public health.
AB  - Communication is a tool that can be used to promote public health. The case of
      tobacco illustrates, however, that behavior change can only be advocated, not
      ensured. The tobacco industry has focused on individual- and societal-level
      actions that effectively sabotage antismoking campaigns. Health communication
      researchers should pay special attention to how politics is subverted, the
      principle of freedom of speech is abused, message framing encourages the
      continued marketing of cigarettes, and tobacco advertising swamps public health
      messages in both quantity and style. The field of health communication should do
      two things to help counter this campaign. First, we should make a concerted
      effort to refute the arguments offered by the tobacco companies. Second, we
      should continue to take action on four levels--as individuals, as responsible
      citizens, in support of organizations, and to create societal changes that will
      reduce the use of tobacco.

PMID- 10947371
TI  - No health leadership.

PMID- 10947372
TI  - Diffusion of innovations theory and work-site AIDS programs.
AB  - Four case studies of the adoption of work-site AIDS programs are investigated,
      two of which were modifications of the Centers for Disease Control and
      Prevention's Business Responds to AIDS (BRTA) program. AIDS work-site programs
      were mainly initiated by the four study companies as a result of the efforts of a
      champion (defined as an individual who gains attention and resources for an issue
      in a system) or the occurrence of a tragic event, such as a company employee
      contracting AIDS. The BRTA program is an innovation that has not yet reached
      critical mass, which is the point after which further rates of adoption occur
      rapidly in a self-sustaining process.

PMID- 10947373
TI  - Childbirth and infant development knowledge gaps in interpersonal settings.
AB  - The knowledge gap hypothesis predicts that infusions of information into an
      environment will lead to knowledge gain by groups with higher socioeconomic
      status (SES) at rates that outpace the knowledge gain of lower SES groups,
      leading to a growing relative gap between them. Four information source variables
      were examined in the present study: education, baby care experience, friend and
      relative networks, and interpersonal communication in a parent education setting.
      Study subjects were mothers and fathers in Minneapolis, Minnesota, and mothers in
      Belfast, Northern Ireland. In the sample, the classic pattern of widening gaps
      due to education was not supported by time trend data, although one-time data
      showed gaps. The interpersonal communication condition contributed most to
      knowledge levels and to widened knowledge gaps.

PMID- 10947374
TI  - The quality of interactive computer use among HIV-infected individuals.
AB  - This study examined how HIV-infected individuals used an interactive health
      software package called CHESS (Comprehensive Health Enhancement Support System).
      CHESS packages information and support in a variety of ways; the research
      examined how a subset of users whose posttest scores in a larger randomized trial
      showed significant improvement in quality of life compared on use patterns of
      CHESS with those who did not improve. The evidence presented here points to the
      nature of CHESS use more than it does to the amount of CHESS use. Those whose
      quality of life improved were among the most involved in their use of CHESS
      information tools. That is, even though Discussion Group accounted for the
      majority of all CHESS uses and time spent with the system, total use and
      Discussion Group use appeared less important than use of the information tools,
      especially if that use was at least somewhat sustained and involved.

PMID- 10947375
TI  - Health communication on the Internet: an effective channel for health behavior
      change?
AB  - This article presents a theoretical rationale for using the Internet to conduct
      persuasive public health interventions. Through an examination of the conceptual
      bases of persuasion, it is posited that the World Wide Web and other Internet
      based resources have many of the characteristics necessary for persuasive
      communication and may, in fact, constitute a hybrid channel that combines the
      positive attributes of interpersonal and mass communication. The notion that the
      Internet features many of the persuasive qualities of interpersonal communication
      makes it a prime candidate for the application of key behavioral science theories
      and principles to promote healthier behaviors. The broad reach that the Internet
      shares with many mass communication channels indicates an economy to Internet
      based efforts to communicate with large audiences. It is concluded that if the
      Internet can be used for persuasive health communication and its reach continues
      to expand, it is time for public health professionals to explore the design and
      evaluation of Internet-based interventions directed at health behavior change.

PMID- 10947376
TI  - The lure of ecstasy.

PMID- 10947377
TI  - Music on the brain. Experts still don't know how and why tunes tickle our fancy-
      but new research offers intriguing clues.

PMID- 10947378
TI  - Between the lines. Too many headlines about cancer "cures" are overblown--here's
      how you can evaluate them.

PMID- 10947379
TI  - Building in ethics at the American Medical Association: a case study in purpose,
      structure, and management.
AB  - Ethics is becoming institutionalized. And many questions are raised thereby. Can
      ethics help institutions? What problems are involved in being an institutional
      ethicist? What are the appropriate connections and boundaries between
      institutions and ethicists? How do responses to these questions help guide the
      institutional structures that must be built to accommodate ethicists' presence?
      The following case study of creating an institute for ethics at a major national
      medical association and of concurrently building up existing ethics structures
      provides a case study in which these questions received some context-specific
      answers.

PMID- 10947380
TI  - Opinions and use of advance directives by physicians at a tertiary care hospital.
AB  - The physician-patient relationship is an essential part of end-of-life planning,
      including discussions of advance directives (AD). Physicians likely to encounter
      AD issues with their patients were identified and queried as to their knowledge,
      opinion, and experience with ADs. Though most physicians felt ADs were helpful to
      both physicians and patients, considerably less were familiar with hospital
      policies and the different types of ADs. Formal education in the use and function
      of ADs also appears to be lacking, suggesting a need to improve the way in which
      ADs are addressed during medical training.

PMID- 10947381
TI  - The impact of genetic technologies on perceptions of disability.
AB  - Advances in human genetics will profoundly affect many medical specialties,
      including obstetrics, genetics, internal medicine, pediatrics and family
      medicine. Studies show that communication between health care professionals and
      patients is biased, in part, by the professionals' prior experiences, knowledge,
      and attitudes toward disability. Little research has been performed to assess
      these attitudes in the context of genetic disability. The authors present: (1) a
      brief overview of the development in genetic technologies and disability, (2) a
      review of the literature around health care provider knowledge and attitudes
      focusing on disability, (3) a discussion of current disability education in
      medical curricula, and (4) suggestions for preparing health care providers to
      deal with issues of genetics and disability.

PMID- 10947382
TI  - The Holy Grail and health care.
AB  - As we prepare to embark upon this new millennium, we do not meet the new age as
      "tabula rasa." Rather, some of the myths and legends of the last still resonate
      within us. And they resound not just to entertain, but to awaken us to the deeper
      mysteries of our lives. One of these current mysteries is the pervasive malady of
      our health care system. This article will briefly sketch the legend of the Holy
      Grail. We will then examine some of the deeper meanings of it in Jungian
      perspective and then bring the story to bear on the health care industry.

PMID- 10947383
TI  - Continuous quality improvement in contract research organizations--managing
      improvement processes.
AB  - The challenge of quality improvement extends beyond traditional service delivery
      organizations. This article, the second in a two-part series (see QMHC 7:3,
      Spring 1999, 7-21 for the first part) focuses on training and empowerment,
      leadership and statistical process control, and the contribution of these factors
      to the success of CROs in the pharmaceutical and biotechnology industry. The
      importance of each is presented along with specific illustrations from operating
      CROs.

PMID- 10947384
TI  - Application of incremental change strategies in chiropractic and
      multidisciplinary clinical settings for quality improvement.
AB  - Care for low back pain remains a clinical enigma. Its high prevalence and cost to
      the system warrants attention for improvement. Although, no major recent clinical
      breakthroughs for resolving back pain have emerged, reducing unnecessary tests,
      eliminating useless or harmful practices, preventing care dependence, and
      enhancing coping skills can be useful goals for improving patient outcomes.
      Quality Improvement (QI) approaches can serve as bridge between clinical
      intuition and large scale science. Three chiropractic delivery settings including
      two teaching clinics and one large multidisciplinary spine care center
      incorporated QI approaches as part of an initiative to improve low back pain
      care. All clinics were able to implement sustainable process and outcomes
      improvements.

PMID- 10947385
TI  - Continuous quality improvement and the process of writing for academic
      publication.
AB  - OBJECTIVE: To improve their academic publication productivity by understanding
      the process of writing and setting long-run productivity goals. METHODS: We used
      the thinking and methods of continuous quality improvement and a national survey
      of associate professors of Family Medicine about their level of productivity at
      the time of their promotion to Associate Professor. RESULTS: Barriers to writing
      vary. The process from idea to publication takes well over a year on average. The
      average number of publications associated with successful promotion in Family
      Medicine ranges from 10 to 14 with substantial variation. CONCLUSION: Knowing the
      time until the promotion decision, the expected level of productivity, the death
      rates of started papers, and the duration of time between start to publication
      allows one to develop a long-range plan for publication productivity.

PMID- 10947386
TI  - QMHC interview with James C. Dechene, JD.

PMID- 10947387
TI  - Clinical governance and NICE: a close relationship.

PMID- 10947389
TI  - Criteria for determining optimal time of discharge after total hip replacement.
AB  - Total hip replacement is a common and expensive procedure and any attempt to
      shorten the length of hospital stay safely is desirable. This paper proposes a
      scoring system specifically designed for this patient population, to determine
      the optimal timing of safe discharge and post-acute care placement. The authors
      discuss the implications for the quality of patient care.

PMID- 10947388
TI  - Clinical governance development needs in health service staff.
AB  - This paper reports on a study to ascertain the development needs in terms of
      clinical governance of 220 health service staff across all the key professions
      from primary and secondary care, including chief executives and clinical
      governance leads. Interviews suggested that the development of clinical
      governance was progressing through the structures created by the leads, and that
      there was considerable goodwill shown towards it in most of the interviews
      conducted. Of the participants 69 per cent had heard of clinical governance,
      though detailed knowledge was rare. The author suggests that development overall
      needs to be carried out using a multi-disciplinary and multi-agency approach
      where possible, perhaps using pathways of care. It needs also to take account of
      the expressed fears from medical staff of discussing their care in a multi
      disciplinary setting, and of the two potential conflicting themes that are
      apparent to chief executives of change towards no-blame cultures, while
      encouraging account-ability and the recognition of risk.

PMID- 10947390
TI  - Outcome-directed clinical practice in lumbar spine surgery.
AB  - Outcome audits describe the current level of clinical performance and direct
      change in clinical practice. The outcome measures used should be not only
      relevant and easily understood but also available to all interested parties, e.g.
      patients, clinicians and commissioners of health. The results of audits can be
      used to set the standard from which clinical practice can be monitored and
      improved. An expectation of likely outcome also gives the patient the opportunity
      of being able to make a fully informed choice. This audit using prospective data
      examines and compares the outcome of surgery for degenerative lumbar spine
      disease over a two-year period. The results allow more accurate information to be
      given to patients, areas of service development to be identified and changes in
      clinical practice to be made.

PMID- 10947391
TI  - A cost-effectiveness study of changing medical practice in early pregnancy.
AB  - Until recent years women with symptoms consistent with miscarriage either
      referred themselves or were referred by their doctors to the local Accident and
      Emergency (A&E) department. This generally resulted in admission to a
      gynaecological ward and delayed treatment. This paper examines the costs and
      benefits of an early pregnancy assessment clinic (EPAC), at a teaching hospital
      in North East England, to deal with the complications in the first trimester. The
      data show clear benefits together with cost savings. There is an unambiguous
      policy recommendation to implement the proposed clinic. The paper examines the
      delivery of service provision and the impact on referral patterns to the A&E
      department and raises the issue of care provision at the margin. Finally, the
      authors show the results of an evaluative survey of the clinic from returns of a
      questionnaire sent to and completed by local general practitioners.

PMID- 10947392
TI  - Quality of health and medical information on the Internet.
AB  - This article examines some of the problems associated with health and medical
      information available via the Internet. An overview is provided of gateway
      services that seek to provide access to high quality materials. Quality
      principles for health and medical Internet-based materials are highlighted and
      suggestions are offered for evaluating sources of information retrieved via the
      Internet. The article concludes that, although there is undeniably a vast
      quantity of useful material available via the Internet, the principles of basing
      health care on the best available evidence still apply and potential users need
      to critically appraise any information they wish to use.

PMID- 10947393
TI  - Gender discrimination within the reproductive health care system: Viagra v. birth
      control.

PMID- 10947394
TI  - Consumer-directed prescription drug advertising: effects on public health.

PMID- 10947395
TI  - Searching for the Holy Grail: the Human Genome Project and its implications.

PMID- 10947396
TI  - Current legal intervention regarding "experimental" treatments must be changed:
      an analysis of high doses of chemotherapy with autologous bone marrow
      transplantation for breast cancer patients.

PMID- 10947397
TI  - Domestic partnership benefits: why not offer them to same-sex partners and
      unmarried opposite sex partners?

PMID- 10947398
TI  - Objective employee assessments--establishing a balance among supervisory
      evaluations.
AB  - Objectivity, predictability, and consistency in a supervisor represent character
      traits that are recognized and appreciated by employees. When evaluating
      employees, these attributes assume added significance. This article outlines a
      methodology, the Quartile Rating Index (QRI), for objectively addressing
      disparities in the rating habits of various supervisors when evaluating the work
      of employees under their supervision.

PMID- 10947399
TI  - Front-line training: a health care imperative.
AB  - Training departments in health care institutions are faced with the problem of
      providing increased services despite reduced budgets. The increased educational
      needs are the result of organizational reengineering, mergers and acquisitions,
      technical advances, and the increasing reliance on less qualified employees. One
      solution to this dilemma is to make better use of managers and experienced
      workers as trainers. Keys to success include the ability to convince managers
      that they will benefit from their expanded roles, and to motivate workers to
      share their knowledge and skill with their team-mates in a cross-training
      endeavor.

PMID- 10947400
TI  - Integration of nurse executives into executive level administration in Utah
      hospitals.
AB  - Nurse executives (NEs) in Utah acute care hospitals perceive that they are
      integrated into executive level administration. This perception is shared by NEs'
      career supporters and hinderers. To integrate NEs, influential colleagues used
      active methods, especially involvement. NEs add value to the administrative team
      by combining clinical and managerial expertise. NE integration is manifest in
      decision making, participation and interaction. Continued integration depends
      upon commitment from the chief executive officer (CEO), leadership in
      organizational change, addressing "glass ceiling" issues, and NEs' continuous
      demonstration of competence.

PMID- 10947401
TI  - Case in health care management: "the all-or-nothing participator".

PMID- 10947402
TI  - Understanding and managing integrated delivery networks.
AB  - This article presents a guide for "managing managed care." To be successful in
      the transition from the fee-for-service payment system to capitation, the manager
      first needs to understand the five roles (the players), and their integration.
      The five roles are the employer, the insurer, the primary care physician, the
      specialist physician, and the hospital. Once a health care manager understands
      the dynamics between these roles and their involvement in operations such as
      finance, contracting, and utilization review, managed care can then be managed.
      This guide is also beneficial to managers for understanding how to work with
      someone in another role.

PMID- 10947403
TI  - Pre-employment decision trees: job applicant self-election.
AB  - Human resource administration is an instrumental factor in determining the degree
      of organizational success. This is especially true in the labor-intensive health
      care industry, which uses teams of health care providers to deliver treatment and
      services. A key function of human resource management is recruiting, since the
      quality of health care treatment is positively correlated with the quality of
      employees. Therefore, the recruiting function can consume a disproportionate
      share of organizational resources. This article discusses how managers can reduce
      the amount of resources spent dealing with inappropriate job applicants by using
      the Pre-Employment Decision Tree, which directs pre-applicants to self-elect to
      apply or not apply, given the degree of fit between the pre-applicant and the
      organization.

PMID- 10947404
TI  - An examination of employer-provided benefits in the health care industry.
AB  - Organizations that depend on a highly-skilled, stable workforce must be attuned
      to the needs of their employees and provide adequate compensation and benefits
      that enhance job satisfaction and lessen job mobility. Hospitals, like other
      organizations that compete for hard-to-find workers, use both traditional and non
      traditional benefits to attract and keep skilled employees. This nationwide
      survey of hospital human resource managers assesses the types of benefits offered
      to health care workers and gauges the perceived impact of those benefits on job
      satisfaction and employee retention. Survey findings reveal that certain basic
      benefits, such as health insurance, are provided to all hospital employees. Other
      benefits, such as signing bonuses and reimbursement of relocation costs, are used
      as inducements to attract individuals in hard-to-fill job categories.

PMID- 10947405
TI  - The anatomy of a decision.
AB  - There is a decision-making pattern that applies in all situations large or small,
      though in small decisions the steps are not especially evident. The steps are:
      gathering information, analyzing information and creating alternatives, selecting
      and implementing an alternative, and follow up on implementation. The amount of
      effort applied in any decision situation should be consistent with the potential
      consequences of the decision. Essentially all decisions are subject to certain
      limitations described as constraints, forces, or circumstances that limit one's
      range of choices. Follow-up on implementation is the phase of decision making
      most often neglected, yet it is frequently the phase that determines success or
      failure. Risk and uncertainty are always present in a decision situation, and the
      application of human judgment is always necessary.

PMID- 10947407
TI  - A manager asks: old issues resurfacing as new problems.

PMID- 10947406
TI  - Why the health care industry should fight union organization and the high cost
      the industry will pay if its fight is unsuccessful.
AB  - The health care industry is being hit hard with an aggressive effort by outside
      unions to organize health care employees. The interest of health care workers in
      union organization and their receptiveness to the unions' messages has grown
      substantially over the last five years--with negative effects on health care
      workers and the health care industry as a whole. This article addresses union
      trends in health care, discusses specific cases and their outcomes, and makes
      recommendations on what the health care industry can, and should, do to preserve
      a union-free work environment.

PMID- 10947408
TI  - Don't go with the flow.

PMID- 10947409
TI  - Investing in the human resource.

PMID- 10947410
TI  - To err is human: to forgive, un-American.

PMID- 10947411
TI  - A 20th century forecast of 21st century healthcare trends.
AB  - John Naisbitt, preeminent social forecaster and author of Megatrends, the New
      York Times 1982 number-one bestseller, has been accurately describing the future
      for the past three decades. This June, Naisbitt will share some his world view
      with individuals attending HFMA's Annual National Institute in Orlando, Florida,
      where he will give the opening keynote address. On December 31, 1999, while most
      of the world waited for the Y2K horizon to spread across the globe, Naisbitt
      spoke with Healthcare Financial Management about the future, particularly with
      respect to some of the subjects he tackles in his most recent book, HIGH
      TECH.high touch. Specifically, does technology free us from the constraints of
      the physical world, or does it tie us down to machines? Does it save time in our
      day-to-day lives or merely create a void we feel compelled to fill with even more
      tasks and responsibilities? How does it affect the delivery of health care? And
      with recent developments in genetic engineering now raising the possibility of a
      future that will someday be free of birth defects, disabilities, and disease,
      what then will be natural, what will be artificial, and what will it truly mean
      to be human?

PMID- 10947412
TI  - Developing an IDS-based disease-management program for the frail elderly.
AB  - IDSs that own a health plan or enter a full-risk-sharing contract with a payer
      are in an position to benefit from developing disease-management programs that
      reduce acute care admissions. Full-risk assumption allows an IDS to realize cost
      savings due to more cost-effective care management that offset revenue lost due
      to reduced acute care services. Crozer-Keystone Health System (CKHS) in Delaware
      County, Pennsylvania, implemented a disease-management program for frail elderly
      enrollees in its Medicare + Choice plan, MedCare Plus. Projected first-year
      savings were estimated at about $619,000 over 1,200 member months. First-year
      results showed a 36 percent reduction in acute care admissions, with savings of
      $242,749 over 613 member months. The difference between actual results and
      projected savings was attributed to social and other factors not accounted for in
      the cost-benefit analysis. Still, lost revenues from acute care admissions were
      more than offset by the savings realized.

PMID- 10947413
TI  - Improve--rather than lose--your risk-taking entity.
AB  - When an HMO transfers financial risk to a provider risk-taking entity such as a
      physician-hospital organization (PHO), independent physician association (IPA),
      large medical group, or other provider contracting organization, it sometimes
      also transfers responsibility for administrative functions, such as claims
      processing. As a result, these providers risk financial problems related to
      medical costs, pricing, and underwriting strategies, as well as administrative
      efficiency. Financial managers should be aware of key indicators and processes
      that identify such problems to be able to take action before losses occur.

PMID- 10947414
TI  - New and clarified safe harbors may ease certain provider transactions.
AB  - The recent final rule issued by the Office of Inspector General adds eight new
      safe harbors to the Federal antikickback statute to the 13 currently in force.
      This final rule also clarifies six of the original 11 safe harbors published in
      1991. In general, safe-harbor provisions to the antikickback statute specify
      payments that will not provide a basis for criminal prosecution or for exclusion
      from the Medicare or state healthcare programs. While safe harbors are very
      narrow and transactions must meet each requirement of an applicable safe harbor
      to be protected, the new final rule should help facilitate certain financial
      arrangements between provider organizations. It may, however, prohibit other
      arrangements.

PMID- 10947415
TI  - Building a demand-driven, vendor-managed supply chain.
AB  - Vendor-managed inventory (VMI) software can help both stand-alone and IDS-based
      hospitals significantly reduce supply-chain management costs. The software tracks
      an organization's actual supply demand and generates automatic purchase orders,
      providing the supplies on an as-needed basis. As a result, a hospital's inventory
      carrying and purchase-order processing costs may be reduced significantly. To
      make optimum use of the VMI software, IDSs and hospitals first need to ensure
      that their methods of collecting data on supply consumption are efficient and
      accurate. They then need to either establish a relationship with a distributor
      offering VMI capability or, if the organization is a large IDS with its own
      distribution center, acquire the software for internal use. A collaboration with
      a distributor requires establishing effective electronic communications for data
      sharing.

PMID- 10947417
TI  - Home health agencies should prepare for prospective payment.

PMID- 10947416
TI  - Cost analysis helps evaluate contract profitability.
AB  - A cost-accounting analysis can help group practices assess their costs of doing
      business and determine the profitability of managed care contracts. Group
      practices also can use cost accounting to develop budgets and financial
      benchmarks. To begin a cost analysis, group practices need to determine their
      revenue and cost centers. Then they can allocate their costs to each center,
      using an appropriate allocation basis. The next step is to calculate costs per
      procedure. The results can be used to evaluate operational cost efficiency as
      well as help negotiate managed care contracts.

PMID- 10947418
TI  - From alliances to outsourcing: making good connections.

PMID- 10947419
TI  - Reaping the benefits of mentorship.

PMID- 10947420
TI  - Attracting physicians to your underserved communities.

PMID- 10947421
TI  - Maximizing your vendor relationships.

PMID- 10947422
TI  - The framework for a successful merger.

PMID- 10947423
TI  - Managing your messages.

PMID- 10947424
TI  - Quality customer service: it's everyone's job.

PMID- 10947425
TI  - The ethics of compliance hotlines.

PMID- 10947426
TI  - Health reform and technological change: shifting hospitalization patterns for
      four procedures in Manitoba.
AB  - This study used Manitoba data from 1991 to 1996 to assess the effects of health
      reforms and technological advances on hospitalization patterns, patient
      mortality, and readmission rates. Cholecystectomy and hernia repair served as
      indicators of response to both new technology and health reforms, while
      appendectomy and hysterectomy helped gauge the impact of health reforms alone.
      Neither the introduction of new technology (i.e. laparoscopy) nor the health
      reform initiatives (i.e. shorter hospital stays) adversely affected surgical
      volumes, postsurgical mortality, or postsurgical readmissions.

PMID- 10947427
TI  - Predictors of job stress and satisfaction among hospital workers during re
      engineering: differences by extent of supervisory responsibilities.
AB  - After two years of rapid organizational change within a large teaching hospital,
      83 percent of workers remained employed there. Among these "survivors," job
      satisfaction decreased and job stress increased regardless of whether they were
      employed in a supervisory position. This article examines the predictors of job
      satisfaction and job stress for managers, for people who indicated that they
      supervised others but were not managers, and for workers. There are areas of
      commonality in predictors across these groups, as well as some differences by
      level of supervisory responsibility. Examining and modifying job characteristics
      associated with high stress could result in healthier hospital work environments.

PMID- 10947428
TI  - Clinical practice guidelines: the need for improved implementation strategies.
AB  - Although substantial resources have been spent developing clinical practice
      guidelines, little effort has been made to evaluate the effectiveness of their
      implementation. In the absence of effective implementation, CPGs will have
      minimal impact on changing behaviours. This article critically reviews the
      literature and identifies a number of reasons why these guidelines have not been
      implemented successfully. If CPGs are to have a positive impact upon clinical
      behaviour and practice, then more aggressive and positive implementation
      strategies are indicated. Five key ingredients for successful implementation of
      quality CPGs are identified and recommended.

PMID- 10947429
TI  - Challenges in providing comprehensive and coordinated care to HIV/AIDS patients:
      a Canadian perspective.
AB  - This article focuses our attention on the means by which healthcare is provided
      to HIV-infected patients who require comprehensive and coordinated care to
      address the variety of changing and challenging needs presented by the acquired
      immunodeficiency syndrome (AIDS). Improved clinical management of HIV infection
      over the past decade, with antiretroviral agents, protease inhibitors and
      prophylactic therapies against opportunistic infections has transformed HIV
      infection from an acute to a chronic illness. Many individuals with AIDS are now
      living longer with more chronic conditions. Concomitant with the transformation
      of HIV infection from an acute to a chronic illness comes the challenge to
      provide effective, humane and economical care to patients with chronic conditions
      that continue to reside in the community, within a healthcare delivery system
      that has evolved to treat patients with acute diseases.

PMID- 10947430
TI  - An access to care center as a learning organization.
AB  - The Durham Access to Care (DATC) is one of the new streamlined vehicles for the
      delivery of integrated home-based and community-based health services across
      Ontario. Management and staff in this change transition have undertaken to become
      a learning organization. To implement this visionary process leadership qualities
      and style is key. This article gives a brief account of DATC and its move to
      becoming a learning organization and the author's observational reflections of an
      effective leadership style.

PMID- 10947431
TI  - Developing a clinical value compass to monitor urology outcomes at the Toronto
      East General Hospital.

PMID- 10947432
TI  - Health administration and the Canadian military. Interview by Matthew D.
      Pavelich.

PMID- 10947433
TI  - Stiffed by an HMO (sound familiar?).

PMID- 10947434
TI  - "Dad always was a fighter".

PMID- 10947435
TI  - My "deadbeat" patient made me a bundle.

PMID- 10947436
TI  - Now I know how patients get lost in the system.

PMID- 10947437
TI  - "I cut myself, doctor--but it doesn't look quite right".

PMID- 10947438
TI  - When a DNR order can be therapeutic.

PMID- 10947439
TI  - I hung out my shingle--and waited.

PMID- 10947440
TI  - Don't treat a relative? I'm glad I did.

PMID- 10947441
TI  - The patient who healed me.

PMID- 10947442
TI  - Countersuits can stop frivolous lawsuits.

PMID- 10947443
TI  - Straightforward UR--or a "machine of denial"?

PMID- 10947444
TI  - "Keep it simple, stupid!".

PMID- 10947445
TI  - Happy together: what makes a practice endure?

PMID- 10947446
TI  - Save thousands a year on medical supplies.

PMID- 10947447
TI  - A son's dilemma, a doctor's ordeal.

PMID- 10947448
TI  - Call is a waste of time.

PMID- 10947449
TI  - Clinton wants Medicare anti-fraud effort expanded; labs focus on legislative
      priorities.

PMID- 10947450
TI  - Testing on demand. Are laboratories and consumers ready?

PMID- 10947451
TI  - Bladder cancer markers. Current availability and the future standard of care.

PMID- 10947452
TI  - New quality guidelines for laboratories.

PMID- 10947453
TI  - Push is on to reduce medical errors; additional money wanted for the CDC; new
      needlestick report offers guidance.

PMID- 10947454
TI  - Committee on Medicare payment methodology for clinical laboratory services meets.

PMID- 10947455
TI  - The risk of transfusion-transmitted prion infections.

PMID- 10947457
TI  - Mission (almost) impossible: merge 2 hospital labs in 6 months.

PMID- 10947456
TI  - Toward optimal PT use.

PMID- 10947458
TI  - U.S. hospitals mired in bureaucracy: 10 roadblocks to change.
AB  - Given the dot.com revolution in health care, advancing medical technology, and
      dissatisfaction with managed care, fundamental change is the order of the day in
      U.S. hospitals. Some hospital leaders are responding effectively to these new
      century challenges. But too many only tinker with existing systems, hoping to get
      by with choices that are comfortable, conventional, and convenient. Meanwhile,
      the sharks of dwindling public confidence and lost political support circle ever
      closer. The vice president of medical affairs (VPMA) is positioned at the vertex
      of disparate organizational, interpersonal, and external forces and can lead the
      way in recognizing and removing common roadblocks delaying needed change.
      External obstacles include: (1) Too much regulation; (2) too many attorneys; and
      (3) theatrical local TV newscasts. Internal factors include: (4) A natural fear
      of change; (5) arguing when we do not really disagree; (6) Cake Committee
      management mentality; (7) over-aggressive downsizing; (8) natural conflict in
      choosing a health care ethic; (9) the past; and (10) lack of trust. Hospital
      leaders need to effectively act, not just think, "outside the box."

PMID- 10947460
TI  - How to kill a clinic merger.

PMID- 10947459
TI  - Merging, de-merging, and emerging at Deaconess Billings Clinic.
AB  - Complexity theory offers a powerful model for effective mergers of health care
      organizations that differs substantially from customary approaches. Exploring how
      Deaconess Billings Clinic in Montana evolved from two separate and very different
      cultures provides insight into how organizations can apply a complex adaptive
      system (CAS) model of mergers to create more truly integrated health care
      systems. DBC's merger illustrates the phenomenon of emergence in complex systems,
      whereby structures arise that are not a synthesis of the pre-existing cultures or
      the result of a new culture being imposed. Instead, the merger is understood as
      an ongoing, self-organizing process appropriately characterized by fits and
      starts, feelings of uncertainty, and other natural challenges of change and
      growth. By squarely surfacing the distinct cultures of the organizations through
      abundant interaction, relationship building, and information flow, differences
      can be creatively transformed, resulting in deep-seated change and the emergence
      of a genuine, shared health care system culture.

PMID- 10947461
TI  - Organizational synergy in medical groups.
AB  - True synergy, as an organizational design, is uncommon in medical groups. This
      article addresses the experiences of a medical group that practiced an extreme
      form of synergy--the total equality of its physicians--since its inception almost
      30 years ago. Synergy is the close coordination of the efforts and resources of
      individuals working together so that the performance of the whole is greater than
      the sum of the parts. Why use synergy in organizational design? By flattening the
      hierarchical levels, synergy addresses key issues of power (control, resource
      allocation, planning) and money (salary, bonuses, benefits), treating all
      physicians as equal partners. It also ensures access to the highest-quality
      candidates because the lure of equality, ownership, and permanence is so
      powerful. Synergy in medical groups works best where there is: A clearly stated
      mission and vision statement, as well as specific goals and objectives; careful
      selection of associates; a small group of between seven and nine members; a short
      term duration of ten years or less; and a certain simplicity, whereby the group
      avoids risk-prone ventures or projects that distract it from its original mission
      and vision.

PMID- 10947462
TI  - The health care consumer gospel according to Harvard Business School: a talk with
      Regina Herzlinger, DBA. Interview by Richard L. Reece.

PMID- 10947463
TI  - Cutting to the chase: what physician executives need to know about HIPAA.
AB  - All health care providers, plans, and clearinghouses will be affected by the
      federally mandated uniform standards for administrative transactions. This
      article presents distilled core information about the Health Insurance
      Portability and Accountability Act (HIPAA) legislation--the standards, penalties
      for violations, and status of final rules. It also raises several key unsolved
      issues of which clinicians, executives, and health care providers must be aware
      so they can prepare and plan for the upcoming changes. HIPAA is intended to
      improve the efficiency and effectiveness of the health care system, as well as to
      increase the protection and confidentiality of individually identifiable health
      information. The costs of making the transition to the legislated standards and
      processes remain a worrisome factor. Although there are two years before these
      standards must be implemented, and cost and compliance issues resolved, work has
      already begun in many health institutions to identify and address them.

PMID- 10947464
TI  - The HIPAAcratic oath: do no harm to patient data.
AB  - Physician executives need to prepare their organizations for the next great
      system-wide challenge--HIPAA, the Health Insurance Portability and Accountability
      Act of 1996. Organizations will have to plan for and execute a compliance program
      with the same vigor and system-wide participation as they did for Y2K. This
      article provides a brief overview of HIPAA, emphasizing the privacy and security
      components that will be the biggest challenge for physician executives. Physician
      leaders must become actively involved in the policymaking process to ensure a
      balanced approach to protecting the confidentiality of health information, while
      giving providers optimal access to data to make informed decisions on patient
      care and management. Ignoring HIPAA is simply not an option.

PMID- 10947465
TI  - Effective health care corporate compliance.
AB  - The pace and intensity of oversight and investigation of health care
      organizations has greatly increased at all levels. Well run organizations with
      ethical management committed to following all laws and regulations are still at
      risk for compliance violations and punitive penalties. Under the Federal
      Sentencing Guidelines, organizations with an "effective" corporate compliance
      program may receive reduced penalties. The seven components of an effective
      program as defined in the guidelines are: (1) Standards and procedures; (2)
      oversight responsibilities; (3) employee training; (4) monitoring and auditing;
      (5) reporting systems; (6) enforcement and discipline; and (7) response and
      prevention. Lack of a compliance program needlessly exposes the organization to
      an avoidable risk of damage from non-compliance--whether intentional or not.
      Moreover, an effective program can contribute to the efficient operation of the
      organization and be a key piece of its corporate culture.

PMID- 10947466
TI  - Associations and bureaucracies.
AB  - Hospitals are institutions in which private physicians admit their patients to
      receive care that could not be provided at home. In order to understand how the
      organization of such hospitals can function, it is necessary to be clear about
      the distinction between two types of medical practice. Health care professionals
      (including doctors, nurses, therapists, etc.) may engage in private practice with
      patients who choose to be treated by them and with whom they have a private,
      confidential relationship. Or they may be employed in treatment institutions
      (mainly hospitals) in which they provide professional services under prescription
      by a treating physician. In private practice, professionals are free standing.
      They may join associations to pursue common interests. But as members of
      associations, they do not work for each other, are not accountable for each
      others work, and are not in manager and subordinate relationships. If, however,
      they work for a hospital, then they become employees within a bureaucracy,
      working for a salary, and subordinate to a manager. The implications for
      physician executives are discussed, with illustrations of the types of authority
      that they require to have an effective working relationship with treating
      physicians.

PMID- 10947467
TI  - Ready for the storm.
AB  - The coming decade is likely to be more turbulent than any we have faced. In fact,
      the basic structures and roles of health care may begin to shift and dissolve in
      ways that we cannot begin to predict. In turbulent times, long-term plans are
      vulnerable to fundamental shifts in the environment. Planning recedes in
      importance compared to preparing--nurturing the institutional and individual
      capacity for change. Rigid planning is about power and control. Preparing is
      about unleashing the strengths of each person on the crew. Self-development is
      largely a matter of recognizing what your strengths are, learning to live in
      those strengths, while nurturing the abilities that do not come naturally.
      Leadership is largely a matter of creating an environment that helps your crew
      work from their strengths and supports them in their weaker areas.

PMID- 10947469
TI  - Is it our turn to be CEO yet?
AB  - Physician executives continue to have ambitions for the health care CEO role,
      despite the difficult economic times. And though few have yet been chosen for the
      position, the expectation is that this will change markedly in the next five to
      seven years. Today, physician executives have legitimate, relevant professional
      experiences that directly qualify them for CEO roles in health initiatives. And
      no executive is more qualified to deal with medical care management issues than
      the physician executive. Key elements of preparedness are: Executive thinking,
      bundling projects, and learning to manage managers. The opportunities will be
      open to those who are ready to take them on.

PMID- 10947468
TI  - Communication tips for the job search and on the job.
AB  - Listening, speaking, and nonverbal skills are the most important success factors
      in getting a job or being effective in your current position. If you don't
      communicate well, your technical knowledge won't ever be put to good use.
      Recruiters, hiring organizations, and bosses are looking for people who can play
      well with others and can sell. Playing well with others involves listening and
      having self-control about what you say. To sell yourself and your ideas or
      products, you must speak well. You also must be well-groomed, look energetic, and
      sound reasonably happy to be at work. Good listeners: Stop talking; ask open
      ended questions; para-phrase, restate, or summarize some of what the person had
      said; and talk about feelings. Effective speakers: Have voice mail etiquette; are
      courteous and tactful; don't react to a verbal attack; don't engage in verbal
      attacks; use the right amount of words; don't say too much; prepare ahead of
      time; and decide whether they should speak or write their message. And remember
      the power of body language or non-verbal skills--how you look and sound. Experts
      estimate that 65 to 90 percent of what you communicate is nonverbal.

PMID- 10947470
TI  - Managed care and downstream risk: placing the provider and the patient at-risk.

PMID- 10947471
TI  - Who = am I2. Introspective scientists are probing the mystery of human
      consciousness.

PMID- 10947472
TI  - Tweaking nature's repair kit. One's own cells may be the best medicine.

PMID- 10947473
TI  - Conquering pain. Treatments for body and mind break a cycle of agony.

PMID- 10947474
TI  - Soothing the littlest patients. Doctors focus on easing pain in kids.

PMID- 10947475
TI  - Body mass weighs in against childhood fat.

PMID- 10947476
TI  - The downside of dissemination.

PMID- 10947477
TI  - Getting the focus and the group: enhancing analytical rigor in focus group
      research.
AB  - In the literature on focus groups, far more attention has been devoted to how
      groups are organized and conducted than to issues of analysis. Although
      exploitation of group dynamics is touted as a virtue of focus groups, there is
      very little guidance in the literature with respect to how differences between
      group and individual discourse impact the analysis and interpretation of focus
      group data. In this article, the authors describe analytical challenges inherent
      in the interpretation of focus group data and suggest approaches for enhancing
      the rigor of analysis and the reliability and validity of focus group findings.

PMID- 10947478
TI  - Losing the plot: narrative construction and longitudinal childbirth research.
AB  - This article seeks to explore the ways in which theories of narrative might be
      significant in the study of childbearing. The event of childbirth and the process
      of women becoming mothers have major significance for individual biographies and
      are publicly defined. The medicalization of childbearing and the placing of a
      natural event into a pathological illness model has repercussions for the ways in
      which women experience and make sense of the event. The complex interweaving of
      public and lay narratives that surround this period of transition can lead to
      bafflement and the eventual construction of personal counternarratives. The
      context in which narratives are managed is explored.

PMID- 10947479
TI  - Participative observation: standing in the shoes of others?
AB  - This article argues that participant observation is more than mere method and in
      need of greater theoretical attention. This is particularly true for its more
      participative forms, which are inseparable from assumptions about the role of the
      body in the generation of knowledge. Drawing on fieldwork experience, parallels
      are noted between participative observation and the clinical practice of nursing,
      for example, their reliance on physical involvement, their claims to experiential
      knowledge, and the associated theoretical assumptions they share, such as a
      reciprocity of perspective between subject and object. Such assumptions need to
      be examined if the knowledge learnt through participation is to carry-weight.

PMID- 10947480
TI  - Metasynthesis of qualitative research on living with HIV infection.
AB  - Qualitative studies of people living with HIV infection are crucial for providing
      direction for practice and research because they provide the emic perspective. As
      more of these qualitative studies are conducted, researchers are challenged to
      develop ways to synthesize the findings for research and clinical practice. The
      purpose of the metasynthesis described in this article was to understand the
      experience of adults living with HIV infection as described in published
      research. Findings from the studies were categorized into six overarching
      metaphors: (a) finding meaning in HIV/AIDS, (b) shattered meaning, (c) human
      connectedness, (d) focusing on the self, (e) negotiating health care, and (f)
      dealing with stigma.

PMID- 10947481
TI  - The standpoint of storyteller.
AB  - The legitimacy of an interest in illness narratives that is therapeutic,
      emancipatory, and pre-occupied with ethics is defended in response to Atkinson's
      critique of this interest as a blind alley. The value of storytelling as
      complementary to story analysis is argued, and the importance of recognizing
      one's own standpoint is emphasized. The conclusion considers how qualitative
      methods can inform changing relationships between illness, health, medicine, and
      culture.

PMID- 10947482
TI  - The changing face of phenomenological research: traditional and American
      phenomenology in nursing.
AB  - In recent years, phenomenological researchers in nursing have become concerned
      about the differences between traditional European phenomenology and the way
      phenomenology is frequently conducted in nursing. Indeed, Crotty asserts that
      much of the phenomenology conducted by nurses cannot be phenomenology because it
      does not espouse the constructionist epistemological position regarded by Husserl
      as essential to phenomenology. This article explores the differences between
      traditional European and American phenomenology and argues that the latter
      approach extends the phenomenological project in valuable and meaningful ways
      that are particularly appropriate for the health sciences.

PMID- 10947483
TI  - Evaluating interpretive inquiry: reviewing the validity debate and opening the
      dialogue.
AB  - Designing and carrying out effective and valid research are the desired goals of
      all researchers, and demonstrating the trustworthiness of one's dissertation
      research is a requirement for all doctoral candidates. For qualitative
      researchers, reaching the desired goal and meeting the requirement of
      trustworthiness become particularly problematic due to the considerable debate
      about what it means to do valid research in the field of qualitative inquiry.
      This article reviews the various approaches to the validity problem in the hope
      of turning this debate into a dialogue. Validity is traced from its origins in
      the realist ontology and foundational epistemology of quantitative inquiry to its
      reformulations within the lifeworld ontology and non-foundationalism of
      interpretive human inquiry. Various recent qualitative approaches to validity are
      considered, and interpretive reconfigurations of validity are reviewed.
      Interpretive approaches to validity are synthesized as ethical and substantive
      procedures of validation.

PMID- 10947484
TI  - Conducting focus groups in developing countries: skill training for local
      bilingual facilitators.
AB  - Many countries of the world are characterized by the use of two or more
      languages, and qualitative research is usually conducted in indigenous languages;
      however, bilingual facilitators often do not have any experience in research
      studies or in conducting focus group discussions. This article presents a 4-day
      skill-training workshop for local facilitators in which they learn the role of
      moderator, recorder, and observer and acquire research skills during role playing
      and during a pretest of the study population. Developed over several years of
      field experience, this technique has proven successful in collecting reliable
      data in situations when time is limited, when participants speak indigenous
      languages, and when bilingual facilitators have no background in research and
      lack focus group skills. The advantages of this training are that it is low cost
      and fast and permits a careful translation of the data. Moreover, because
      facilitators are involved in the collecting and analyzing of the data, their
      input provides the investigator with a valuable understanding of the findings
      from an emic perspective.

PMID- 10947485
TI  - Qualitative and quantitative analyses of psychological distress: methodological
      complementarity and ontological incommensurability.
AB  - Rigorous qualitative and quantitative methodologies have been used for the
      development of a multidimensional scale dedicated to the measurement of
      psychological distress. A comparison between the idioms of distress or the
      cultural forms through which French Quebecois express their distress (qualitative
      constructs) and the nonorthogonal factors derived from explanatory and higher
      order factorial analyses (quantitative constructs) illustrates the possibilities
      of complementarity between qualitative and quantitative approaches. The
      comparison shows that these two operationalizations of the concept of
      psychological distress are founded on incommensurable representations of
      distress. This article concludes that this representational dilemma of distress
      as a lived language or as an empirical reified entity leads to an ontological and
      a teleological incommensurability.

PMID- 10947486
TI  - The importance of achieving additional drug benefits at a reasonable cost. A
      review of the fluoxetine years.
AB  - Fluoxetine continues to be remarkably successful; greater volumes of this drug
      are sold than for any other antidepressant in the world. Prozac has also become a
      household name. In this article we examine the circumstances that surround this
      success, and the evidence base that supports it. Rather than being a major step
      forward in the treatment for depression, the evidence for fluoxetine and for the
      selective serotonin reuptake inhibitors in general suggest at best a modest
      improvement in tolerability, with no evidence of improved efficacy. We note that
      the road to success was not problem free for fluoxetine, and highlight the
      response of the sponsor in the development of subsequent drugs for CNS disorders.

PMID- 10947487
TI  - Cost effectiveness of combination HIV therapy: 3 years later.
AB  - Since 1997, expert panel guidelines for HIV care have recommended the use of
      combination antiretroviral therapy with at least 3 antiretroviral drugs. Several
      studies have examined the cost effectiveness of 3-drug combination antiretroviral
      regimens for the treatment of HIV infection. Analyses comparing a 3-drug protease
      inhibitor-containing regimen with a 1- or 2-drug non-nucleoside reverse
      transcriptase inhibitor regimen have consistently yielded incremental direct cost
      estimates ranging from $US10,000 to just over $US13,000 per year of life saved.
      In Western societies, such an incremental cost per year of life saved compares
      favourably with chronic therapy for other diseases and argues for the adoption of
      these drugs by payors and policy makers. The reason for this favourable cost
      effectiveness ratio appears to be the decrease in opportunistic complications and
      hospitalisation associated with the effective use of combination antiretroviral
      therapy. Whether this initial benefit will be maintained is not yet known. Other
      comorbid illnesses such as hepatitis C or renal failure may subsequently increase
      the cost of HIV care, and some analyses suggest that resistance may develop to
      these drugs over the long term. In addition, studies are needed to assess the
      cost effectiveness of these therapies in developing countries where the expense
      of these drugs appears to put them out of reach. The collection and analysis of
      economic data will continue to be needed as newer HIV therapies become available
      and the HIV healthcare environment evolves. Quantifying medical care costs and
      calculating cost effectiveness involve assessing a moving target. Economic
      analyses of HIV infection must evolve in tandem with therapeutic changes to
      continue to be relevant to policy makers, payors of care, and those who provide
      and receive HIV care.

PMID- 10947488
TI  - Economic burden of irritable bowel syndrome. Proposed strategies to control
      expenditures.
AB  - It has been suggested that the annual direct costs for irritable bowel syndrome
      (IBS) are now around $US41 billion in the 8 most industrialised countries. This
      paper reviews the data on calculations of direct costs. The true economic burden
      is unclear, as there are insufficient data on indirect costs other than
      absenteeism from work and intangible costs cannot be estimated, particularly
      since presenters with IBS constitute only a subset of the patients with such
      symptoms in the community. Strategies to reduce direct costs must include
      physician and patient education, paramedical-based education and therapy, lay
      support groups, early consideration of psychosocial issues and psychological
      treatments, avoidance of unnecessary investigations and optimising the doctor
      patient relationship. Indirect and intangible costs could be effectively reduced
      by novel, effective (not only efficacious) therapies.

PMID- 10947489
TI  - Inference for the cost-effectiveness acceptability curve and cost-effectiveness
      ratio.
AB  - The aim of this article is to consider Bayesian and frequentist inference methods
      for measures of incremental cost effectiveness in data obtained via a clinical
      trial. The most useful measure is the cost-effectiveness (C/E) acceptability
      curve. Recent publications on Bayesian estimation have assumed a normal posterior
      distribution, which ignores uncertainty in estimated variances, and suggest
      unnecessarily complicated methods of computation. We present a simple Bayesian
      computation for the C/E acceptability curve and a simple frequentist analogue.
      Our approach takes account of errors in estimated variances, resulting in
      calculations that are based on distributions rather than normal distributions. If
      inference is required about the C/E ratio, we argue that the standard frequentist
      procedures give unreliable or misleading inferences, and present instead a
      Bayesian interval.

PMID- 10947490
TI  - Potential savings in the cost of caring for Alzheimer's disease. Treatment with
      rivastigmine.
AB  - OBJECTIVE: To estimate savings in the cost of caring for patients with
      Alzheimer's disease (AD) during 6 months, 1 year and 2 years of treatment with
      rivastigmine. An intermediate objective was to estimate the relationship between
      disease progression and institutionalisation. DESIGN AND SETTING: We assessed the
      relationship between Mini-Mental State Examination (MMSE) score and
      institutionalisation using a piecewise Cox proportional hazard model. To estimate
      cost savings from treatments lasting 6 months, 1 year and 2 years, estimates of
      the probability of institutionalisation were integrated with data from two 6
      month phase III clinical trials of rivastigmine and a hazard model of disease
      progression. MAIN OUTCOME MEASURES AND RESULTS: Our data suggest that savings in
      the overall cost of caring for patients with mild and moderate AD can be as high
      as $US4839 per patient after 2 years of treatment. Furthermore, the probability
      of institutionalisation increases steadily as MMSE score falls. Among our study
      individuals, age, race, level of education and marital status were significant
      predictors of institutionalisation, whereas gender had little effect.
      CONCLUSIONS: Using rivastigmine to treat AD results in a delay in disease
      progression for patients who begin treatment during the mild or moderate stages
      of the disease. By delaying the probability that a patient will be
      institutionalised, the cost of caring for AD patients can be significantly
      reduced.

PMID- 10947491
TI  - Costs incurred by patients undergoing advanced colorectal cancer therapy. A
      comparison of raltitrexed and fluorouracil plus folinic acid.
AB  - BACKGROUND: To assess the cost effectiveness of healthcare interventions from a
      societal perspective, it is necessary to include costs such as patients' travel
      costs and the opportunity cost of patients' time spent consuming healthcare.
      OBJECTIVE: To analyse patients' travel and time costs associated with 2
      alternative drug therapies for advanced colorectal cancer: raltitrexed and
      fluorouracil plus folinic acid (leucovorin) [5FU + FA]. DESIGN AND SETTING: The
      analysis is based on a prospective substudy within a multinational randomised
      controlled trial of raltitrexed versus 5FU + FA. PATIENTS AND PARTICIPANTS: 495
      patients with advanced colorectal cancer were enrolled in the trial, 270 of whom
      completed the questionnaire on costs. METHODS: Data were collected within the
      trial to estimate the numbers of journeys made to and from hospital by patients
      and the time lost from usual activities over the period of therapy. A subset of
      patients were asked to complete a questionnaire to provide the information
      necessary to value time and travel costs in monetary terms. These data, together
      with UK transport costs and forgone time values, were used to value the transport
      and opportunity costs of time of all patients in the trial. RESULTS: The total
      travel cost per patient was statistically significantly higher in the 5FU + FA
      group (p < 0.001; median of 31.50 Pounds with raltitrexed, 96.00 Pounds with 5FU
      + FA; 1997 prices). Overall time cost per patient was also higher in the 5FU + FA
      group (p = 0.005; median of 168.80 Pounds with raltitrexed, 224.04 Pounds with
      5FU + FA). Adding the two gives a median total cost per patient of 206.08 Pounds
      [interquartile range (IQR) 108 Pounds to 482 Pounds] among patients randomised to
      raltitrexed and 342.25 Pounds (IQR 214 Pounds to 555 Pounds) for those in the 5FU
      + FA group (p < 0.001). The sensitivity analysis showed that, even under extreme
      assumptions, raltitrexed imposed fewer time and travel costs on patients. These
      cost differences are likely, in part, to reflect the longer treatment times for
      5FU + FA patients (median 16.9 vs 12.7 weeks). CONCLUSIONS: Different
      chemotherapy regimens for advanced colorectal cancer can impose different travel
      and time costs on patients. Over the period of treatment in a randomised
      controlled trial of 495 patients, those randomised to 5FU + FA were found to have
      a median travel plus time cost 136 Pounds per patient higher than those
      randomised to raltitrexed.

PMID- 10947492
TI  - Initial treatment choice in depression: impact on medical expenditures.
AB  - OBJECTIVE: The purpose of this study was to examine the economic outcomes
      associated with initial treatment choice following a diagnosis of depression.
      METHODS: Insurance claims data were used to classify patients into one of 4
      treatment cohorts: no therapy, psychotherapy, drug therapy and combination
      therapy. Potential sample selection bias was accounted for by using a 2-stage
      econometric estimation procedure where initial treatment choice was estimated
      using a multinomial logistic regression model in the first stage, and total and
      mental healthcare costs were estimated in ordinary least squares regression
      models in the second stage. Log predicted costs from the second stage were
      compared to determine the relative costs associated with each cohort. RESULTS:
      Significant differences (p < 0.008) in total costs were found between the
      combination therapy (log predicted cost = 9.526) and psychotherapy cohorts (log
      predicted cost = 8.120) in the analysis that included all observations (n =
      9110). In the analysis that included patients who initiated therapy with a non
      mental health provider (n = 2673), the drug therapy cohort (log predicted cost =
      8.238) was found to be significantly more costly as compared to the no therapy
      cohort (log predicted cost = 7.788). CONCLUSIONS: These results indicate that
      after controlling for both observed and unobserved factors, total healthcare
      costs may be higher in patients who initiate therapy with drug therapy and
      combination therapy as opposed to no therapy or psychotherapy. In addition, the
      finding that patients initially receiving psychotherapy alone tend to have higher
      mental healthcare costs but lower total healthcare costs than other patients may
      indicate that psychotherapy has an impact on comorbid illness and may
      subsequently reduce total healthcare costs.

PMID- 10947493
TI  - Cost analysis of the treatment of schizophrenia in the UK. A simulation model
      comparing olanzapine, risperidone and haloperidol.
AB  - OBJECTIVE: To compare the costs of 2 atypical drug therapies (olanzapine and
      risperidone) with one another and with a conventional antipsychotic (haloperidol)
      in the treatment of schizophrenia. DESIGN AND SETTING: The analysis is based on a
      simulation model with parameter values taken mainly from clinical trial data in
      patients with schizophrenia, and was conducted within a UK context. RESULTS: The
      3 therapies are approximately cost neutral over a 5-year period (olanzapine
      35,701 Pounds, risperidone 36,590 Pounds and haloperidol 36,653 Pounds). There is
      evidence of greater efficacy with the atypical drugs [average percentage of 5
      years with Brief Psychiatric Rating Scale (BPRS) scores < 18: olanzapine 63.6%,
      risperidone 63.0% and haloperidol 52.2%]. The cost and efficacy differences
      between the 2 atypical drugs are too small to rank them in terms of cost
      effectiveness. Extensive sensitivity analysis does not change any of the main
      conclusions. CONCLUSIONS: Given evidence of efficacy gains to the atypical drugs,
      these represent cost-effective treatment options. Prospective data from nontrial
      treatment settings would help substantiate the model findings.

PMID- 10947495
TI  - Building regional health care networks in Europe.

PMID- 10947494
TI  - Cost effectiveness of competing strategies to prevent or treat GORD-related
      dysphagia.
AB  - OBJECTIVES: The variety of influences that contribute to the occurrence of
      dysphagia in gastro-oesophageal reflux disease (GORD) provide the physician with
      many options to intervene in the pathophysiology of the disease process. The aims
      of the present analysis were to compare the relationships between the costs and
      effectiveness of competing therapeutic interventions in preventing dysphagia.
      METHODS: Dysphagia was modelled as the focal point of multiple influences leading
      to its development. The costs associated with different forms of drug therapy
      were based on the average wholesale prices listed in the Red Book of 1998.
      Procedural costs were estimated from Medicare reimbursements. Different treatment
      options were assessed by their incremental cost-effectiveness ratio. RESULTS:
      Lifestyle modifications, treatment with prokinetic agents or antacids reduce the
      occurrence of dysphagia by 22, 21 or 25%, respectively. Acid inhibition results
      in a 57 to 89% reduction of dysphagia, depending on treatment with histamine-2
      receptor antagonists (H2RAs) or proton pump inhibitors (PPIs). Oesophageal
      dilation results in a reduction ranging between 54 and 81%. The incremental ratio
      of cost effectiveness associated with prokinetic agents or H2RAs is much higher
      than that of PPIs. Based on the concept of extended dominance, therefore,
      prokinetic drugs and H2RAs do not constitute cost-effective means to prevent
      dysphagia and should be excluded in favour of treatment with PPIs. CONCLUSIONS:
      An economic analysis of various treatment strategies to reduce the risk of GORD
      related dysphagia indicates that PPIs are the most cost-effective means to
      prevent its occurrence.

PMID- 10947496
TI  - Partnership for excellence in asthma care: evidence-based disease management.
AB  - Partnership for Excellence in Asthma Care, a practical example of evidence-based
      disease management, was launched by Egleston Scottish Rite Children's Health Care
      System. The process of development and implementation of evidence-based practice
      guidelines for the outpatient management of asthma is described. Methods to
      influence physician practice patterns and the preparation of feedback reports are
      discussed. The method for measuring outcomes and preliminary outcome data are
      shared.

PMID- 10947497
TI  - Retooling practitioners in the information age.
AB  - For "retooling" one needs two components: new hardware and new skills. "Hardware"
      in the Medical Informatics environment includes not only hardware in a narrow
      definition, but operating and application software, network services, security
      services etc. Since the sixties, Medical Informatics has slowly moved from
      fighting computer hardware to fighting the complexity of application software and
      its installation. Thus the hardware part in the retooling process has changed but
      did not decrease in importance. Retooling medical professionals also means
      retraining of professionals--often a major investment. Regarding the necessary
      skills, we have to adapt existing medical curricula and continuous medical
      education (CME). So far, these have not successfully been adjusted to the
      retooling needs. The international community has to address these matters,
      specifically in the context of medical curriculum and CME.

PMID- 10947498
TI  - Towards a health telematics infrastructure in the European Union.
AB  - Over the last decade information and communication technologies--telematics
      technologies--have demonstrated their potential to improve the quality, access
      and efficiency of health care. Health telematics applications are presently
      revolutionizing the developments not only in diagnosis, treatment, surveillance
      and rehabilitation of patients, but also on the side of the more collective
      aspects of health care and health prevention such as clinical trials,
      epidemiology and health education. Moreover, for the first time in the history of
      health care the emerging Health Information Infrastructure (HII), i.e. telematics
      networks together with a set of technologies, health telematics applications and
      services, is making possible the rapid dissemination and sharing of health
      information and research results. This is leading to knowledge creation and to
      promotion of innovative approaches based on evidence collected in medical
      practice all over the world.

PMID- 10947499
TI  - Transferring research through high performance computing.

PMID- 10947500
TI  - Interaction between clinical research and patient data.

PMID- 10947501
TI  - Digital library research and application.
AB  - The last decade has seen an exponential rise in the amount and the nature of
      information that is available on the Internet. Internet and World Wide Web
      technology have raised many technical as well as social and economic issues. The
      paper begins with a description of the recent digital library research initiative
      funded by the U.S. federal government. Digital library research addresses a host
      of informatics issues relevant to the current Internet-based environment. The
      paper continues with a discussion of some problems in information access,
      including a discussion of the potential of the Unified Medical Language System
      for navigating among multiple biomedical information systems. Next, some issues
      in creating Web-accessible resources for health care consumers are addressed,
      with a focus on recent work at the National Library of Medicine, including a
      description of the MEDLINEplus system. The paper ends with a brief discussion of
      some implications of digital library research for the health informatics
      community.

PMID- 10947502
TI  - Knowledge and change in health care organizations.
AB  - All of us realize that these are times of high change in virtually every health
      care system, regardless of size or location. As part of this change process, many
      health care systems are taking a serious look at the area that has evolved as
      knowledge management. While change may be mandatory, progress is definitely
      optional.

PMID- 10947503
TI  - Incorporating knowledge into commercially available systems.
AB  - The ways in which a potential commercial 'user' treats different knowledge types
      are explored in this paper. The issues are dealt with by the pragmatism with
      which a marketing manager might evaluate an opportunity. Academics are typically
      motivated by drivers that are different from a commercial 'push'. Thus
      partnership is needed for a productive compromise; addressing questions such as
      why should academic institutions let commercial organizations have their
      intellectual capital. The paper considers issues of hand-over, product
      maintenance and a continued development partnership, especially in a volatile
      [Inter] net-based age.

PMID- 10947504
TI  - Opportunities for improving quality in the health care industry.
AB  - This paper discusses the current state of health care quality and describes some
      of the factors that are hindering efforts to move toward evidence-based practice.
      The President's Advisory Commission on Consumer Protection and Quality spent one
      year looking at the state of health care quality and developed a set of
      recommendations to tackle the serious quality problem in the health care
      industry. The Institute of Medicine has started an initiative, Quality of Health
      Care in America Project, which is addressing many of the quality of care areas
      identified by the President's Advisory Commission on Consumer Protection and
      Quality. This paper discusses the work of these two groups and concludes with key
      issues in the advancement of quality health care.

PMID- 10947505
TI  - Information services that make patients co-producers of quality health care.
AB  - A new era of consumerism is emerging. Increasingly educated consumers are
      demanding convenience, choice, and self-efficacy or self-mastery. These educated
      consumers are causing businesses in a variety of service industries, including
      health care, to change their business design in response to changing consumer
      preferences. Increased consumer pressures to change health care business designs
      are evidenced by a flood of state and federal legislation and managed care
      organizations broadening their networks and product offerings to respond to
      consumer complaints about lack of choice. These pressures are also evidenced by
      educated patients, armed with information they have gathered via the Internet and
      other sources going to their physician and saying, "Together let's figure out how
      I can do this myself." In addressing the entire scope of illness cost drivers
      that are causing health care expenditures to spiral upward in this country,
      providers need not overlook the role that the effective relay of information
      plays in moving the patient from their traditional roles as resource and customer
      to more effective roles as co-producer and partner in the transformation process.
      Health care organizations and professionals must experience a paradigm shift in
      both their approach to providing health care and in their understanding of the
      new role of the patient as co-producer.

PMID- 10947506
TI  - State legislatures busy with telemedicine measures.

PMID- 10947507
TI  - $28 million DHHS grant for diabetes care goes to Columbia University.

PMID- 10947508
TI  - Digital echocardiography--managing massive data flows, thousands of studies over
      a multi-site network.

PMID- 10947509
TI  - Australian hospital's web-based program speeds Dx and Rx of spider bites.

PMID- 10947510
TI  - A net present value analysis of neonatal telecardiology.

PMID- 10947511
TI  - Federal regulators sound warnings about eHealth, cite areas of potential
      regulation.

PMID- 10947512
TI  - Fiberoptics: the next level up in teleradiology.

PMID- 10947513
TI  - IC.USA: expanding intensive care beyond the enterprise.

PMID- 10947514
TI  - The last word. Odds ratios, outcomes research, and rural telemedicine.

PMID- 10947515
TI  - An innovative approach to enterprise-wide monitoring.

PMID- 10947516
TI  - Inspector General grants protection from anti-kickback statute to telemedicine
      relationship--a victory for grantees!

PMID- 10947517
TI  - When is an HIV infection prevented and when is it merely delayed?
AB  - HIV prevention programs are typically evaluated using behavioral outcomes.
      Mathematical models of HIV transmission can be used to translate these behavioral
      outcomes into estimates of the number of HIV infections averted. Usually,
      intervention effectiveness is evaluated over a brief assessment period and an
      infection is considered to be prevented if it does not occur during this period.
      This approach may overestimate intervention effectiveness if participants
      continue to engage in risk behaviors. Conversely, this strategy underestimates
      the true impact of interventions by assuming that behavioral changes persist only
      until the end of the intervention assessment period. In this article, the authors
      (a) suggest a simple framework for distinguishing between HIV infections that are
      truly prevented and those that are merely delayed, (b) illustrate how these
      outcomes can be estimated, (c) discuss strategies for extrapolating intervention
      effects beyond the assessment period, and (d) highlight the implications of these
      findings for HIV prevention decision making.

PMID- 10947518
TI  - The effect of the Weekly Reader on children's knowledge of current events.
AB  - Analyses of data drawn from 2,331 urban and suburban elementary students ages 8
      to 12 in Chicago, Houston, Boston, and San Francisco suggest that children who
      have higher reading levels and greater exposure to current events through
      communication media (television, newspapers, newsmagazines, discussions) have
      more knowledge and greater understanding of current events within classrooms, as
      measured by a 29-item current events knowledge test. Children in lower elementary
      classrooms (Grades 2 and 3) with the Weekly Reader periodical present appeared to
      have higher levels of current events knowledge, even after controlling for key
      classroom variables. The effect of the Weekly Reader is less for children in
      upper elementary classrooms (Grades 4 through 6) because they tend to receive
      more current events information from other communication materials.

PMID- 10947519
TI  - Assessing the impact of administrative policy on use of deadly force by on- and
      off-duty police.
AB  - Deadly force research typically does not distinguish between shootings by on-duty
      and off-duty police. This article uses Philadelphia police shooting data from two
      time periods (1970-1978 and 1987-1992) and a unique quasi-experimental design to
      examine the comparative effects upon on- and off-duty police shootings of an
      administrative policy that limited police shooting discretion but that did not
      address questions of police weapons carrying and access to firearms. The article
      draws important distinctions between when to shoot and carry administrative
      policies and considers their impact on deadly force by on- and off-duty police.

PMID- 10947520
TI  - The Dartmouth Assertive Community Treatment Scale (DACTS). A generalizability
      study.
AB  - Generalizability theory was used to assess the reliability of the Dartmouth
      Assertive Community Treatment Scale (DACTS), which was developed to assess
      treatment reliability to assertive community treatment (ACT). Program staff and
      local evaluators who were participating in a national demonstration program to
      serve homeless mentally ill clients provided data. The total scale score for the
      DACTS demonstrated acceptable internal consistency and interrater reliability.
      Although the stability of the total DACTS score was quite low, many items on the
      DACTS were quite stable. The generalizability analyses provide additional detail
      on the effects of site, occasion, and site by occasion interactions on the
      reliability of the DACTS.

PMID- 10947521
TI  - Modeling intervention efficacy for high-risk women. The WINGS Project.
AB  - This study evaluates the effectiveness of two strategies--communication and
      condom skills training--for increasing condom-protected sex in a sample of 510
      high-risk women ages 17 to 61. Baseline and 3- and 6-month postintervention
      interview data were gathered in three cities participating in a randomized trial
      of a six-session, group skill-building intervention. This analysis was conducted
      for the entire sample and for six subgroups categorized by age, single or
      multiple partners, and history of childhood sexual abuse. The dependent variable
      was the odds ratio of protected sex acts at each follow-up. Structural equation
      modeling was used to estimate effects for two intervention pathways. The pathway
      through condom skills increased the odds of protected sex for the intervention
      group (chi 2 difference = 35, df = 2, p < .05) as well as for all subgroups. The
      pathways through communication were significant for the intervention group (chi 2
      difference = 23, df = 3, p < .05) but fully effective only for participants under
      30 and participants who reported childhood sexual abuse. The effectiveness of
      both pathways diminished at 6 months. WINGS demonstrates that condom skills
      training can increase protected sex for a heterogeneous group of women. Further
      research needs to examine how such skill training translates into use of condoms
      by male partners. To increase the duration of intervention effects, booster
      sessions may need to be incorporated.

PMID- 10947522
TI  - Trainee characteristics and perceptions of HIV/AIDS training quality.
AB  - HIV/AIDS education and training have played a vital role in keeping health
      providers up to date on emerging developments and approaches. This study reports
      findings from seven HIV/AIDS education and training projects. Participants in
      more than 600 training sessions described themselves, their professional
      background, and their general reasons for taking the training. Immediately
      following the training, they also rated the quality of their educational
      experience along several dimensions. Trainee characteristics were related to
      assessments of training quality, using a regression decision-tree analytic
      approach. Although effect sizes were generally small, quality ratings of the
      HIV/AIDS training experiences were associated with certain projects, basic
      trainee demographic characteristics, professional background, and experience in
      the HIV field. Greater understanding about participant characteristics can
      provide clues about how these training experiences are perceived and processed
      and may inform decision making about instructional HIV/AIDS curricula.

PMID- 10947523
TI  - Increasing response rates to a smoking survey for U.S. Navy enlisted women.
AB  - This study examined the effectiveness of several persistent strategies to
      increase the response to a smoking survey among newly enlisted U.S. Navy women.
      The stepped approach, which included the use of incentives, repeated mailings,
      alternative survey administration modes, and reminders, was evaluated in terms of
      effects on response rates and response bias. Demographic and baseline smoking
      related characteristics were compared for those responding on time to the initial
      mailed follow-up survey, reluctant respondents who did not respond initially but
      eventually completed a survey after further prompting, and non-respondents.
      Results showed that incentives and persistent efforts were effective in
      substantially increasing the response among 2,231 eligible participants, more
      than doubling the response rate (from 24.9% to 52.7%). The characteristics of on
      time, reluctant, and non-respondents did not differ significantly in terms of
      sociodemographic characteristics. On the other hand, on-time respondents were
      different from both reluctant respondents and non-respondents in terms of smoking
      related behaviors.

PMID- 10947524
TI  - Utility of a brief self-efficacy scale in clinical training program evaluation.
AB  - Self-efficacy is often studied as a predictor of professional practice behaviors
      or as an outcome of clinical training, using brief scales with little validation.
      This study examines the utility of a brief self-efficacy scale in the evaluation
      of a clinical training program. Subjects were 119 registered dietitians who
      participated in diabetes training. Hypothesized relationships between self
      efficacy ratings and indices of skill mastery, participation in training, and
      subsequent practice change were examined. Self-efficacy ratings after training
      correlated significantly with relevant prior experience (r = .4 and .29, p < .01)
      but not total experience and with knowledge post-test score (r = .21, p < .02).
      Self-efficacy for all 12 program objectives increased significantly after
      training. Post-training self-efficacy for two program objectives correlated
      significantly with self-reported successful practice changes related to those
      objectives (r = .4, p < .04 and r = .51, p < .01). The data suggest that brief
      self-efficacy assessments can contribute meaningfully to clinical training
      program evaluation.

PMID- 10947525
TI  - Contextual influences on learning application in practice. An extended role for
      process evaluation.
AB  - Although process evaluation usually ends with the program, process itself does
      not end. This study analyzed process or contextual influences health
      professionals face when returning from continuing professional education (CPE)
      and attempting to apply learning. Follow-up survey data were analyzed for a
      sample (N = 549) of physicians, nurses, counselors, and rehabilitation
      specialists. Contextual influences studied include resources, encouragement,
      support, opportunity, and authority. Logistic regression analysis found support
      for changes to apply training ideas was a predictor of application for the sample
      as a whole and for all professional groups except one. Encouragement from others
      was a predictor of application for rehabilitation specialists, and opportunity to
      apply learning was a second predictor for nurses. Sufficient resources was not a
      predictor in any models tested. Results indicate that the practice context can
      affect educational outcomes and an extended vision of process evaluation is
      needed to incorporate such variables in the evaluation of CPE.

PMID- 10947526
TI  - Sampling for evaluation. Issues and strategies for community-based HIV prevention
      programs.
AB  - Sampling methods are an important issue in the evaluation of community-based HIV
      prevention initiatives because it is through responsible sampling procedures that
      a valid model of the population is produced and reliable estimates of behavior
      change determined. This article provides an overview on sampling with particular
      focus on the needs of community-based organizations (CBOs). As these
      organizations continue to improve their capacity for sampling and program
      evaluation activities, comparisons across CBOs can become more rigorous,
      resulting in valuable information collectively regarding the effectiveness of
      particular HIV prevention initiatives. The author reviews several probability and
      non-probability sampling designs; discusses bias, cost, and feasibility factors
      in design selection; and presents six guidelines designed to encourage community
      organizations to consider these important sampling issues as they plan their
      program evaluations.

PMID- 10947527
TI  - Infection control outside the hospital: developing a continuum of care.
AB  - Pressures to limit or eliminate more expensive inpatient care have led t he way
      to rapidly expanded use of ambulatory care are extended care services. A
      consensus panel of infection control specialists have devised new recommendations
      on what can be addressed when infections occur outside the hospital.

PMID- 10947528
TI  - Company introduces standards for disease management programs.
AB  - American Healthways, a Nashville-based company that provides disease management
      services recently has released what it calls the nation's first set of standards
      for evaluating disease management programs.

PMID- 10947529
TI  - NCQA moves toward PPO accreditation.
AB  - The National Committee for Quality Assurance has introduced a draft accreditation
      program for preferred provider organizations that focuses on consumer protection,
      access to care, member services, provider credentialing, medical group oversight,
      and plan performance.

PMID- 10947530
TI  - Infectious diseases pose new pressures but provide new opportunities for health
      care.
AB  - Many hospitals are beginning to make inroads in lowering the rates of infections
      occurring throughout their facilities. However, the emergence of new drug
      resistant organisms, shorter stays in hospitals, greater reliance on out-patient
      care, sicker patients, and increasing numbers of invasive surgical procedures
      still stir new concerns about the problems posed by infectious diseases.

PMID- 10947531
TI  - Oversight mechanisms in public managed care programs: from little oversight to
      negotiations to shared decision-making.
AB  - An expanded range of oversight mechanisms is being adopted to hold public human
      service programs more accountable to funding sources as well as consumers, family
      members, and providers. Most of these approaches are hierarchical in nature. Some
      involve negotiated agreements and each is designed to meet certain goals and
      functions. Each utilizes different forms of decision-making. Stakeholders prefer
      to be part of a shared decision-making process. Understanding these underlying
      premises can help to assess the strengths and weaknesses of each method and can
      suggest how to most effectively utilize combinations of approaches to improve
      program performance. Whether we will move toward a new paradigm emphasizing
      participation and collaboration rather than more formal structural approaches is
      yet undetermined but will greatly affect how programs are monitored and evaluated
      in the future.

PMID- 10947532
TI  - For profit versus non-profit: does economic sector make a difference in child
      care?
AB  - The child-care industry in a large, southeastern community serves as this study's
      vehicle for comparing non-profit with for profit dependent care in areas not
      easily observable to clients. The cross-sectional analysis compares child-care
      centers on marketed and actual staff-to-child ratio; staff salary; consistency in
      the child's group environment; staff stability; and extent of parental
      involvement. Findings are based on self-reports of directors and support
      hypotheses derived from the theory that for profit day care centers will use
      their discretionary authority to vary the care environment to achieve profit
      goals despite the potential effect on the quality of the child's environment.
      Further, despite potential cost economies and enhanced quality of care achievable
      as a non-profit entity, few for profit center directors consider becoming non
      profit centers.

PMID- 10947533
TI  - A different model: alternative service delivery for today's diverse communities.
AB  - This article proposes a new model of human services delivery more suited to
      providing services in today's diverse communities. Traditional models of service
      delivery, common in many agencies, are not suited for serving many immigrants,
      gay men and lesbians, many people of color, and others with significant cultural
      differences. An examination of domestic violence in the lesbian and gay
      communities highlights this problem. A description of one program developed to
      provide services to battered lesbians provides the basis for the development of a
      new model of service delivery. This "different" model, more appropriate for these
      more diverse communities, is described here.

PMID- 10947534
TI  - Mandated human services restructuring: a case study in local collaboration from
      Colorado.
AB  - The Colorado State Legislature has undertaken an historic restructuring of human
      services ranging from child welfare, mental health, and nursing services to
      substance abuse prevention, institutionalization, and health care financing.
      Significant steps in this process include an overhaul of child welfare
      legislation, major revisions to legislation affecting group health insurance
      policies, and a restructuring of the state departments that provide human
      services. A Democratic Governor and a Republican-dominated legislature have
      worked together hand-in-hand, although not always harmoniously, in moving these
      changes forward. This article examines the statewide restructuring of human
      services in a case study of how the local planning process was carried out in one
      region of Colorado. A highlight of the case study is the Working Together survey
      administered to participants of the planning committee midway through the process
      and again after the Local Area Plan was developed. In addition, lessons are
      presented from the process instructive for others considering whether to
      undertake significant organizational restructuring. The lesson section focuses on
      the local area planning process and how Colorado may have designed and
      facilitated a more effective process.

PMID- 10947536
TI  - Differences in the role and administrative relationships of medical directors in
      community and migrant health centers.
AB  - This study examined differences in medical directors of Community and Migrant
      Health Centers (C/MHCs) in the United States based on the size of the center,
      including demographics, job characteristics, roles, and their relationship with
      C/MHC administrators and governing boards. Data for this analysis came from a
      1996 cross-sectional survey of Community and Migrant Health Centers medical
      directors. A total of 411 centers (68.3% surveyed) responded to the survey
      including 240 rural centers (67.4%) and 171 urban (68.7%) centers. Small centers
      were categorized as those with three or fewer physicians (n = 136), medium
      centers had more than three but less than eight ETE physicians (n = 14), and
      large centers had eight or more ETE physicians (n = 109). Several differences
      were found regarding the medical directors' roles and relationships with the
      administrator and governing boards on the size of the center. Large C/MHC medical
      directors had more autonomy than did small and medium C/MHC medical directors
      including in the areas of managing clinical staff, the budget, and strategic
      planning activities. They spent more time cultivating community resources than
      small and medium center counterparts and were more likely to possess the
      management skills needed in their role than do those in small and medium centers.
      They also reported a stronger working relationship with the C/MHC administrator
      and had more input with the C/MHC board than small or medium medical directors.

PMID- 10947535
TI  - Revisiting the debate of voluntary versus mandatory HIV/AIDS testing in U.S.
      prisons.
AB  - Many studies examine HIV/AIDS and often there is a lack of consensus among
      researchers and policy-makers regarding the importance of mandatory or voluntary
      testing within a prison setting. This article revisits and extends this
      discussion by presenting arguments and issues related to testing inmates. A
      comparison of selected factors indicated that mandatory testing is an important
      adjunct to minimizing the impact of the spread of the virus both within prison
      and in the non-offender population. An important policy implication for adopting
      mandatory testing is that such a policy allows health care providers to intervene
      early and control the spread of the disease. Potential implications for future
      research and policy are discussed.

PMID- 10947537
TI  - Findings of a three-year retrospective study to investigate prevalence and
      incidence of urinary incontinence and overactive bladder in a typical managed
      care setting.
AB  - This study was conducted in a large, integrated HMO to determine the prevalence
      and incidence of urinary incontinence, identify a demographic profile of patients
      having the UI subgroup condition of overactive bladder, and collect data to
      create an economic cost of illness description regarding current diagnosis and
      treatment practices. Using ICD-9 and CPT codes and prescription drug claims data
      as markers for the disease, subjects were selected for inclusion in the study.
      Resource use cost data was collected from this cohort over a three-year period
      and analyzed for total and mean monthly costs.

PMID- 10947538
TI  - Asthma: an analysis of high-cost patients.
AB  - OBJECTIVE: To examine characteristics of asthma patients who accounted for 80
      percent of national expenditures in 1994 dollars. STUDY DESIGN: Data were
      extracted from a comprehensive data source, the 1987 National Medical Expenditure
      Survey (NMES) of approximately 35,000 individuals. PATIENTS AND METHODS: Persons
      of interest were identified using any occurrence of the ICD-9 code 493 or
      subcategories. Population weighting factors were used to estimate the population
      in the United States who sought care for the treatment of asthma. Two groups were
      identified: a high-cost group, which accounted for 80 percent of the direct
      medical expenditures, and a low-cost group, which represented 20 percent of
      expenditures. All analyses were performed using SUDAAN software, which takes into
      account the complex sampling design used in NMES. RESULTS: Individuals who rated
      their health as poor or fair were more likely to be in the high-cost group, as
      compared with those who rated their health as good or excellent (p < .0009).
      Persons who reported having Medicare, other government, or private insurance were
      more likely to be in the high-cost group as compared to those with Medicaid and
      self-pay (p = .01). A person was more likely to be in the high-cost group if he
      or she used four or more different medications to treat asthma (p < .0001).
      CONCLUSIONS: Persons with asthma are more likely to have greater medical
      expenditures if they use four or more medications and have deteriorated health
      status. Managed care organizations and public programs may find these
      characteristics useful in targeting asthma prevention and management programs.

PMID- 10947539
TI  - Promising pharmacological agents in the management of acute spinal cord injury.
AB  - The search for a pharmacologic treatment of acute spinal cord injury (SCI) dates
      back to the 1960s. It was not until 1990 that the pharmacologic agent
      methylprednisolone demonstrated improved outcomes in humans. Methylprednisolone
      has shown superiority to placebo in humans in two large, multicenter trials, and
      is the standard of care thus far. Other potentially useful agents include
      tirilazad, ganglioside (GM-1), and naloxone. Additional studies are needed for
      these agents to determine the optimal dose and timing of administration.

PMID- 10947540
TI  - Measuring the benefits of clinical decision support: return on investment.
AB  - In an effort to provide high quality care in a more cost-effective manner, health
      care providers have found it necessary to implement a series of decision support
      strategies designed to improve outcomes of care. While each of these strategies
      has measurable benefits, they each come along with additional costs. This article
      will describe a methodology for measuring the costs and direct and indirect
      benefits from decision support activities.

PMID- 10947541
TI  - Enforcement spotlight shines on formularies: is your compliance program ready to
      refute kickback and false claims allegations?

PMID- 10947542
TI  - One more time: please fire marginal employees.
AB  - Managers should not second-guess themselves when contemplating termination of
      marginal employees, i.e., those with sustained poor attitudes or performances.
      Poor performers should not be allowed to disadvantage an otherwise successful
      team; management ought not to retain someone it cannot fully support; and
      termination may be interpersonally excruciating but is organizationally very
      invigorating. This article identifies ten reasons why marginal employees prevail
      and are not dealt with in organizations. Acknowledging these barriers is a
      valuable first step in moving from analysis to synthesis as concerns removing
      them in the future.

PMID- 10947543
TI  - State regulation of pharmacy activities.

PMID- 10947544
TI  - Applying research to health care policy and practice: medical and managerial
      views on effectiveness and the role of research.
AB  - OBJECTIVES: This study explores the way in which doctors and managers think about
      the effectiveness of health care interventions and how this shapes the evidence
      they use to support decision-making. METHODS: Case studies of the introduction of
      three new medical technologies in nine National Health Service (NHS) hospitals
      and health authorities. RESULTS: Effectiveness research provides essential
      evidence on clinical and cost-effectiveness and is used primarily by clinicians
      and public health doctors for this purpose. However, research fails to provide
      the 'evidence' required by managerial decision-makers, whose objectives relate as
      much to the effect of a technology on organisational performance as on patient
      health and well-being. The evidence used to inform technology adoption decisions
      reflects the professional role and objectives of different decision-makers.
      CONCLUSIONS: The assumed relationship between 'research' and 'evidence' for the
      purpose of promoting effective health care does not take account of the wide
      range of objectives pursued by different health care decision-makers and the
      varied sources of 'evidence' they use to support their decisions.

PMID- 10947545
TI  - Cost containment of pharmaceutical use in Iceland: the impact of liberalization
      and user charges.
AB  - OBJECTIVES: Iceland was the first Nordic country to liberalise its drug
      distribution system, in March 1996. Subsequent regulation in January 1997
      increased patients' share of drug costs. The objectives of this study were to
      test the assumptions that liberalizing community pharmacy ownership would lower
      reimbursement costs for the state's Social Security Institute and that increasing
      patient charges would reduce use and, therefore, lower the cost to the Institute.
      METHODS: Based on the assumptions, we built and tested two models using
      interrupted time series designs that contrast the monthly reimbursement costs
      before and after the legislation and regulation took effect. A control variable
      (the number of office visits to general practitioners) was tested to assess other
      events in the health care arena. Monthly data on these variables were provided by
      the Icelandic State Social Security Institute for January 1993 to August 1998 for
      reimbursement costs and to December 1998 for office visits to general
      practitioners. RESULTS: Reimbursement costs have risen steadily throughout the
      period under study. The interrupted time series analysis did not show a
      substantial effect from the legislative change in March 1996 or from the
      regulatory intervention in January 1997. CONCLUSIONS: The main argument used for
      liberalizing community pharmacy ownership in Iceland was built on false
      assumptions regarding the effect on drug reimbursement costs to the state. It
      will be necessary to find more promising interventions to halt the rapidly
      increasing cost of drugs.

PMID- 10947546
TI  - A fair approach to discounting future effects: taking a societal perspective.
AB  - It is usually recommended that future costs and health effects are discounted at
      the same rate, usually 5%. In this paper it is argued that, from a societal
      perspective, this approach may be inappropriate for health effects. Instead of
      basing the discount rate for health effects on that for costs, it should be based
      on the real change in the (societal) valuation of health effects over time. Such
      valuation may change because of increasing life-expectancy and diminishing
      marginal utility of additional health effects over time.

PMID- 10947547
TI  - Legitimate decision making: the Achilles' heel of solidaristic health care
      systems.
AB  - The future sustainability of 'solidaristic' or universal publicly financed health
      systems is frequently said to be threatened by lack of resources as rising demand
      collides with the growing reluctance of the better-off to pay for services mainly
      used by others. Competitive health care arrangements are also regarded as
      threatening solidarity. By contrast, I argue that the main threat to the
      sustainability of such systems lies in the inability of so-called 'advanced'
      societies to develop institutions that are capable of acceptably reconciling
      inevitably scarce resources with individual and collective desires to have all
      the health care we want. Many 'advanced' societies lack, or fail to incorporate
      into their health systems, the range of intermediate institutions that could
      potentially help in more effectively reconciling individual wants with
      collectively determined levels of resources.

PMID- 10947548
TI  - From evidence-based medicine to evidence-based policy?

PMID- 10947549
TI  - RCT-RIP, or, can the pharmaceutical industry survive the genomic revolution?

PMID- 10947550
TI  - An economic evaluation comparing two schedules of antenatal visits.
AB  - OBJECTIVES: To conduct an economic evaluation comparing a traditional antenatal
      visiting schedule (traditional care) with a reduced schedule of visits (new style
      care) for women at low risk of complications. METHODS: Economic evaluation using
      the results of a randomised controlled trial, the Antenatal Care Project. This
      took place between 1993 and 1994 in antenatal clinics in South East London and
      involved 2794 women at low risk of complications. RESULTS: The estimated baseline
      costs to the UK National Health Service (NHS) for the traditional schedule were
      544 Pounds per woman, of which 251 Pounds occurred antenatally, with a range of
      327-1203 Pounds per woman. The estimated baseline costs to the NHS for the
      reduced visit schedule was 563 Pounds per woman, of which 225 Pounds occurred
      antenatally, with a range of 274-1741 Pounds per woman. Savings from new style
      care that arose antenatally were offset by the greater numbers of babies in this
      group who required special or intensive care. Sensitivity analyses based on
      possible variations in unit costs and resource use and modelled postnatal stay
      showed considerable variation and substantial overlap in costs. CONCLUSIONS:
      Patterns of antenatal care involving fewer routine visits for women at low risk
      of complications are unlikely to result in savings to the Health Service. In
      addition, women who had the reduced schedule of care reported greater
      dissatisfaction with their care and poorer psychosocial outcomes which argues
      against reducing numbers of antenatal visits.

PMID- 10947551
TI  - Do clinical practice guidelines reflect research evidence?
AB  - OBJECTIVES: To examine whether existing clinical practice guidelines (CPGs) for
      cholesterol testing reflect research evidence and hence may control or reduce
      costs while maintaining or improving the quality of care. METHODS: A systematic
      search for published and unpublished cholesterol testing CPGs and independent
      critical appraisal of the CPGs by two researchers using a standard checklist.
      RESULTS: In four of the five CPGs analysed, the link between the research
      evidence and the recommendations was not maintained. The appraisal, local
      experience and the literature all suggest that panel composition is an important
      explanation, in that the greater the involvement of clinical experts in the
      development process of the CPGs, the less the recommendations reflected the
      research evidence. Even though their participation is important for CPG uptake,
      clinical expert panels appear to have difficulty limiting CPGs to research-based
      recommendations. CONCLUSIONS: Existing cholesterol testing CPGs are unlikely to
      improve the quality of care while controlling or reducing costs. The problem lies
      not with guideline implementation but with the guidelines themselves. It is
      unclear how best to ensure that recommendations reflect research evidence but
      this is likely to require significant and progressive changes to the current
      guideline development process, including a redefinition of the clinical experts'
      role.

PMID- 10947552
TI  - Weights for waits: lessons from Salisbury.
AB  - OBJECTIVES: This paper describes a waiting list patients' points scheme under
      development in Salisbury, UK, for the fair management of elective inpatient and
      day case waiting lists. The paper illustrates how points can be assigned to
      patients on a waiting list to indicate their relative unmet need, and illustrates
      the impact on case mix and resource use of the implementations of the points
      system versus 'first come, first served'. The paper explores a range of
      philosophical and technical questions raised by the points system. METHODS: The
      Salisbury Priority Scoring System enables surgeons to assign relative priority to
      patients at the time they are placed on a waiting list for elective health care.
      Points are assigned to patients to reflect the rate of progress of their disease,
      pain or distress, disability or dependence on others, loss of usual occupation
      and time already waited. In recognition of the need for resource planning
      alongside the prioritization of elective inpatients and day case waiting lists, a
      range of iso-resource groups has been developed for all procedures on these
      lists. These categorize procedures in terms of their resource use (i.e. bed days
      and theatre time required). RESULTS: In a modelling exercise, application of the
      Salisbury Points Scheme to a 'first come, first served' orthopaedic waiting list
      produced considerable changes in the order of patients to be treated. Only seven
      patients appeared in the first 20 patients to be treated under both regimes. The
      Salisbury Scheme required fewer resources to treat its first 20 patients than
      'first come, first served' and met more Salisbury-defined 'need', but eliminated
      fewer days of waiting from the list. CONCLUSIONS: Development of a points scheme
      and iso-resource groupings opens up opportunities for more sophisticated
      purchasing, based on treating patients in order of unmet need rather than
      according to arbitrary maximum waiting time guarantees, as has been the dominant
      policy on waiting lists pursued in the UK, Australia, and Sweden, to date.
      However, such schemes raise three issues: first, the necessity of defining need
      as a composite of clinical and social factors; second the necessity to determine
      the acceptability of explicit prioritization to both health care professionals
      and patients; third, the thorny issue of whether such prioritization schemes will
      lead to 'gaming' by well-meaning general practitioners and specialists, aiming to
      secure the priority of their own patients and clinical specialty. Rigorous
      piloting of schemes, such as that developed at Salisbury, will be required to
      identify their dynamic effect over time on case mix, waiting time and resource
      use.

PMID- 10947553
TI  - Use of mark-recapture techniques to estimate the size of hard-to-reach
      populations.
AB  - OBJECTIVES: To review the main problems associated with mark-recapture methods of
      population estimation, and to indicate some practical strategies for addressing
      these problems, with illustrations from a study of drug-use prevalence across
      Wales. METHODS: Unnamed identifier data were collected in 1994 on 2610 drug users
      who were in contact with various agencies across Wales: the police, drug
      treatment agencies, needle exchanges, probation services, and agencies reporting
      to the Welsh Drugs Misuse Database. RESULTS: Based on the dependency
      relationships between different agencies' datasets, different estimates of the
      'hidden' populations (not in contact with agencies) were modelled for each
      county, for males and females, for injecting drug users and serious drug users,
      and for those under 25 and those over 25 years of age. Different models were also
      constructed for the same subpopulations, using different agency datasets and
      different criteria of overlap between them, yielding a total of 230 different
      models. CONCLUSIONS: The issues of sample heterogeneity and population definition
      are particularly intractable in mark-recapture studies. Sample heterogeneity may
      be partly addressed by separately modelling different subpopulations to check
      whether they show the same dependency relationships as the main population.
      Population definition may be partly addressed by restricting modelling to
      datasets thought to share roughly congruent population definitions.

PMID- 10947554
TI  - Getting evidence into clinical practice: an organisational behaviour perspective.
AB  - OBJECTIVES: To study the relationship between research evidence and clinical
      behaviour change in the UK National Health Service (NHS) in the period 1995-1997
      by examining the 'careers' of change issues designed to reshape clinical
      practice, the impact of such change efforts, and the factors shaping change
      outcomes. METHODS: Comparative case study methods were used. Four clinical change
      issues were studied using semi-structured interviews (n = 119) and documentary
      analysis in one English NHS region. For each issue, there was an overview semi
      structured interview survey of the issue at regional level, followed by an
      intensive analysis of its impact at local level on the practice of specific
      clinical groups. RESULTS: There was a weak relationship between the evidence base
      and its diffusion. The diffusion and take-up of scientific evidence were shown to
      be socially constructed. Different forms of evidence were differentially accepted
      by individuals and groups. Specific organisational and social factors affected
      this pattern of impact. The general management hierarchy of the NHS played a very
      limited role in enabling evidence-based clinical change. CONCLUSIONS: The
      implementation of evidence-based medicine is a complex and contested process. The
      results of this study confirm a professional dominance model of clinical
      behaviour change and identify tacit expert knowledge as a key power resource in
      shaping the way research evidence influences clinical practice.

PMID- 10947555
TI  - Physician compliance plan risk areas: a comprehensive review.

PMID- 10947556
TI  - Managed care safe harbors.

PMID- 10947557
TI  - HMO liability for the use of financial incentive arrangements in the provision of
      health care.

PMID- 10947558
TI  - Dr. Koop and the greed disease.

PMID- 10947559
TI  - A new way to attack cancer.

PMID- 10947560
TI  - Negotiating worker-client relationships: a necessary step to providing quality
      home health care.
AB  - A qualitative study was conducted to investigate definitions of quality home
      health care and how good quality care was achieved from consumer and provider
      perspectives. Using semi-structured interviews, members of sixteen families and
      their home health aides described the skills required for good quality care.
      While able performance of essential tasks was considered part of quality care,
      relational skills of home health aides were crucial to good quality care.
      Relationships were negotiated between worker and client that were characterized
      as close and preserving of client autonomy. When such relationships were
      achieved, workers were frequently described as insiders in client families. High
      performing aides also undergo a process of intrapersonal negotiation in order to
      give meaning to their work. Implications for recruitment and training of home
      health aides and for measuring quality care in home health are discussed.

PMID- 10947561
TI  - A comparison of home care clients and nursing home residents: can community based
      care keep the elderly and disabled at home?
AB  - Admission cohorts from the Michigan Medicaid Home and Community-Based Waiver
      program and Ohio nursing homes were compared on measures of resource utilization
      including a modified Resource Utilization Groups (RUG-III) system, Activities of
      Daily Living (ADLs), and overall case mix. We found that, contrary to previous
      research, the two samples were remarkably similar across RUG-III categories.
      However, the nursing home sample was more functionally impaired on measures of
      ADL functioning and overall case mix. Results of this study may inform
      policymakers and providers of the potential for maintaining the appropriate
      population in the home with government-funded home care.

PMID- 10947562
TI  - Client satisfaction with service coordinators' provision of home based long-term
      care services.
AB  - This descriptive study investigates the reliability and validity of the Service
      Coordinator Satisfaction Measure (SCSM) which was developed to measure client
      satisfaction with service coordination in a pilot home based long-term care (LTC)
      program. The SCSM measures the subdimensions of service delivery and service
      sufficiency, as well as overall satisfaction with service coordination.
      Reliability testing with a sample of 213 clients indicated that the SCSM had high
      internal consistency (Cronbach's alpha = .86) and validity testing with the SCSM
      and a criterion measure also yielded significant positive correlations (r = .57,
      p < .01). Results showed that clients ranged between being unsure and satisfied
      with their service coordinator. Analysis of the subdimensions in the SCSM
      indicated clients were more satisfied with service delivery than they were with
      service sufficiency, suggesting that clients were somewhat ambiguous about
      assuming a greater role in managing their own home based LTC needs.

PMID- 10947563
TI  - Structure and implementation of comprehensive state preadmission screening
      programs for nursing home applicants: 1978-1994.
AB  - This paper examines the structure and implementation of comprehensive state
      preadmission screening (PAS) programs for nursing home applicants from 1978 to
      1994 in all 50 states and the District of Columbia. A state was considered to
      have comprehensive PAS if a majority of nursing home applicants were screened in
      person by state or contract agency staff. Twenty-six states had implemented these
      programs by 1994, with the most growth taking place during the 1980s. The primary
      changes in program structure were an increased reliance on private providers to
      screen a subset of applicants and a higher percentage of states screening private
      pay applicants. All programs but one referred or authorized the use of community
      based services, while most programs diverted well over 10 percent of nursing home
      applicants.

PMID- 10947564
TI  - The poverty of information systems management in home health agencies:
      implications for survivability.
AB  - Home health agencies are increasingly being challenged to cope with economic,
      financial and clinical pressures. This study examines the extent to which home
      health agencies have cultivated their information systems as an aid for managing
      performance and external forces. Colorado and New Mexico home health agencies
      participated in the research project. The findings indicate that only modest
      investments have been made by respondents in their information systems. The
      typical respondent reports a personal computer-based system which addresses some
      financial reporting data, but which does not emphasize care delivery or
      contextual factors. The implications of these findings for the survivability of
      home health agencies are discussed.

PMID- 10947565
TI  - How to enhance the efficacy of health network growth.
AB  - In almost every American metropolitan area, health executives are busily
      enhancing the efficacy of their health networks by corporately restructuring so
      that their organization can become a fiscally and politically powerful oligopoly
      or a regulated monopoly. When the formation of these alliances are initially
      announced by the local media, they are reported to be vehicles to enhance access,
      social equity and quality of care, and to reduce costs. Since an increasing
      number of these health networks are currently experiencing fiscal, cultural and
      other difficulties, it is critical to study: (a) what factors should be
      considered when developing an effective and efficient health network?; (b) what
      are the practical issues in their strategic formation and management so they
      eventually achieve their full potential?; and (c) why will some divestitures
      among these health networks occur and how will these corporate 'spin offs' impact
      on consumers, providers, insurers and governmental agencies? Within the next
      decade the United States will face some inevitable economic difficulties. At that
      time, enhancing access and reducing costs will become more critical issues for
      health networks. These alliances may then need to become more responsive to
      consumer pressures as the Americans shift their political proclivities from the
      current quasi-competitive to a more quasi-regulatory position. In this context,
      the use of global budgetary targets is discussed as a possible option in the
      United States to constrain costs, an approach used in almost all other western
      industrialized nations.

PMID- 10947566
TI  - Reconsidering clinical accountability. An examination of some dilemmas inherent
      in efforts to bolster clinician accountability.
AB  - The paper critically appraises current efforts to bolster the accountability of
      clinicians. The paper opens with an examination of the values, meaning and rules
      which underpin different accountability systems. Against this background we
      canvass conceptual, practical and ethical issues which need to be addressed if
      efforts to extend the accountability of clinicians are to meet with success.

PMID- 10947567
TI  - Reforming the health sector in Thailand: the role of policy actors on the policy
      stage.
AB  - This paper reports on exploratory research carried out into the processes of
      policy-making, and in particular health sector reform, in the health sector of
      Thailand. It is one of a set of studies examining health sector reform processes
      in a number of countries. Though in the period under study (1970-1996) there had
      been no single health sector reform package in Thailand, there was interest in a
      number of quarters in the development of such an initiative. It is clear,
      however, that despite recognition of the need for reform such a policy was far
      from being formulated, let alone implemented. The research, based on both
      documentary analysis and interviews, explores the reasons underpinning the
      failure of the policy process to respond to such a perceived need. The research
      findings suggest that the policy formation process in Thailand successfully
      occurs when there is a critical mass of support from strategic interest groups.
      The relative power of these interest groups is constantly changing. In particular
      the last two decades has seen a decline in the power of the bureaucratic elites
      (military and civilian) and a related rise in the power of the economic elites
      either directly or through their influence on political parties and government.
      Other critical groups include the media, NGOs and the professions. Informal
      policy groups are also significant. A number of implications for policy makers
      operating under such circumstances are drawn.

PMID- 10947569
TI  - Public insurance substituting for private insurance: new evidence regarding
      public hospitals, uncompensated care funds, and Medicaid.
AB  - This paper examines the impact of public health insurance programs, whether
      structured as subsidies to health care providers (public hospitals and
      uncompensated care reimbursement funds) or as direct insurance (Medicaid), on the
      purchase of private health insurance. The presence of a public hospital is
      associated with a lower likelihood of private insurance for those with incomes
      between 100-200% and 200-400% of the poverty level. Uncompensated care
      reimbursement funds were associated with less purchase of private health
      insurance and a higher likelihood of being uninsured across all income groups.
      More generous Medicaid programs showed both safety-net and crowd out effects.

PMID- 10947568
TI  - From cooperation to competition in national health systems--and back?: impact on
      professional ethics and quality of care.
AB  - Ethical behaviour in health workers is the jewel in the crown of health services.
      Health system policies need to nurture a professional service ethic. The primary
      health care policy envisioned a national health system led by the public sector
      and based on a philosophy of cooperation. A common theme of 'health sector
      reform' in OECD countries, introduced in the context of neoliberalism, has been
      the use of 'managed competition' to increase efficiency. Some countries that
      flirted with health system competition have returned to cooperation. Market
      relationships tend to be oppositional and to stimulate self-seeking behaviour.
      Health system relationships should encourage patient and community centred
      behaviour. The World Bank and bilateral donors have exported health sector reform
      theories from the north to the south, involving privatization and marketization
      policies. This is despite the lack of evidence on their desirability or
      feasibility of implementing them. Private health care has increased in many
      developing countries, more as a result of economic crisis and liberalization than
      specific health sector reforms. Much of this private practice is unlicensed and
      unregulated, and informal privatization has had a damaging effect on health
      worker ethics. The lead policy should be reconstruction of the public health
      system, involving decentralization, democratization and improved management.
      Commonsense contracting of an existing private sector is different from a policy
      of proactive privatization and marketization. Underlying the two approaches is
      whether health care should be viewed as a human right best served by socialized
      provision or a private good requiring governments only to correct market failures
      and ensure basic care for the poor. It is a matter of politics, not economics.

PMID- 10947570
TI  - 'Competition' among employers offering health insurance.
AB  - Most employees contribute towards the cost of employer-sponsored insurance,
      despite tax laws that favor zero contributions. Contribution levels vary markedly
      across firms, and the average contribution (as a percentage of the premium) has
      increased over time. We offer a novel explanation for these facts: employers
      raise contribution levels to encourage their employees to obtain coverage from
      their spouses' employer. We develop a model to show how the employee contribution
      required by a given firm depends on characteristics of the firm and its work
      force, and find empirical support for many of the model's predictions.

PMID- 10947571
TI  - Did the Medicaid expansions for children displace private insurance? An analysis
      using the SIPP.
AB  - Using data from the 1990 panel of the Survey of Income and Program Participation
      (SIPP), we address the question: Did the Medicaid expansions for children cause
      declines in private coverage? We use a multivariate approach that attributes a
      displacement effect to declines in private coverage for children targeted by the
      Medicaid expansions exceeding declines for a comparison group of older low-income
      children. We find that 23% of the movement from private coverage to Medicaid due
      to the expansions was attributable to displacement. There is no evidence of
      displacement among those starting uninsured, leading to an overall displacement
      effect of 4%.

PMID- 10947572
TI  - Medicaid and crowding out of private insurance: a re-examination using firm level
      data.
AB  - While previous research has identified a relationship between expanded Medicaid
      eligibility and falling private health insurance coverage, the exact mechanism by
      which this "crowding out" occurs is largely unexplained. We combine individual
      and firm-level data to investigate possible responses to the Medicaid expansions
      by firms and workers. We find no evidence that the expansions affected employer
      offers of insurance to workers. However, we find some evidence of an effect on
      the probability that a firm offers family coverage, and on the percentage of full
      time workers accepting employer-sponsored coverage offered to them.

PMID- 10947573
TI  - Recent trends in employer-sponsored health insurance coverage: are bad jobs
      getting worse?
AB  - We examine whether the decline in the availability of employer-provided health
      insurance is a phenomenon common to all jobs or is concentrated only on certain
      jobs. We find that declines in own-employer insurance coverage over the 1988-1997
      period are driven primarily by declines in take-up for long-term full-time
      workers and declines in eligibility for new and part-time workers. We also look
      at trends by workers' education level, and see how much of the decline in is
      offset by an increase in coverage through a spouse's policy.

PMID- 10947574
TI  - The future of health economics.
AB  - This paper discusses health economics as a behavioral science and as input into
      health policy and health services research. I illustrate the dual role with data
      on publications and citations of two leading health economics journals and three
      leading American health economists. Five important and relatively new topics in
      economics are commended to health economists who focus on economics as a
      behavioral science. This is followed by suggestions for health economists in
      their role of providing input to health policy and health services research. I
      discuss the strengths and weaknesses of economics, the role of values, and the
      potential for interdisciplinary and multidisciplinary research. The fourth
      section presents reasons why I believe the strong demand for health economics
      will continue, and the paper concludes with a sermon addressed primarily to
      recent entrants to the field.

PMID- 10947575
TI  - Cross-national price differences for pharmaceuticals: how large, and why?
AB  - Bilateral drug price and quantity indexes, based on comprehensive data for seven
      countries (US, Canada, France, Germany, Italy, Japan and the UK), refute the
      conventional wisdom that US drug prices are much higher than elsewhere, for
      Laspeyres (US-weighted) indexes. Previous drug-price comparisons are biased by
      unrepresentative samples and unweighted indexes. Quasi-hedonic regression shows
      that cross-national price differences reflect differences in product
      characteristics and in their implicit prices, which reflect the regulatory
      regime. Strict price regulation systematically lowers prices for older molecules
      and globally diffused molecules. Generic competition lowers prices in less
      regulated regimes, which also have more price-elastic demand.

PMID- 10947576
TI  - Adverse selection and categorical discrimination in the health insurance markets:
      the effects of genetic tests.
AB  - In this paper, the effects of new methods for risk classification, e.g., genetic
      tests, on health insurance markets are studied using an insurance model with
      state contingent utility functions. The analysis focuses on the case of treatment
      costs higher than the patient's willingness to pay where standard models of
      asymmetric information are not applicable. In this case, the benefit from signing
      a fair insurance contract will be positive only if illness probability is low. In
      contrast to the common perception, additional risk classification under symmetric
      information can be efficiency enhancing. Under asymmetric information about
      illness risks, however, there can be complete market failure.

PMID- 10947577
TI  - The willingness to pay for wait reduction: the disutility of queues for cataract
      surgery in Canada, Denmark, and Spain.
AB  - We estimate demand curves for a one month reduction in waiting time for cataract
      surgery based on survey data collected in 1992 in Manitoba, Barcelona, and
      Denmark. Patients answered, "Would you be willing to pay [Bid, B] to reduce your
      waiting time for cataract surgery to less than one month?" Controlling for SES
      and visual status, Barcelonan patients have greater WTP for shortened waiting
      time than the Danes and Manitobans. We estimate the value (in 1992 $) of lost
      consumer surplus due to the cataract surgery queue at $128 per patient in
      Manitoba, $160 in Denmark, and $243 in Barcelona.

PMID- 10947578
TI  - A model of physician behaviour with demand inducement.
AB  - We present a model of the physician-patient relationship extending on the model
      by Farley [Farley, P.J., 1986. Theories of the price and quantity of physician
      services. Journal of Health Economics 5, 315-333] of supplier-induced demand
      (SID). First, we make a case for the way this model specifies professional
      ethics, physician competition, and SID itself. Second, we derive predictions from
      this model, and confront them with the neoclassical model. Finally, we stress the
      importance of considering how SID affects patient welfare in providing an example
      where physicians' ability to induce makes patients better off. To evaluate
      patient welfare, we derive approximations of the patients' welfare loss due to
      physician market power in both the neoclassical model and the inducement model.

PMID- 10947579
TI  - Health care is an individual necessity and a national luxury: applying multilevel
      decision models to the analysis of health care expenditures.
AB  - Health care is neither "a necessity" or "a luxury"; it is "both" since the income
      elasticity varies with the level of analysis. With insurance, individual income
      elasticities are typically near zero, while national health expenditure
      elasticities are commonly greater than 1.0. The debate over whether health care
      is or is not a luxury good arises primarily from the failure to specify levels of
      analysis clearly so as to distinguish variation within groups from variation
      between groups. Apparently, contradictory empirical results are shown to be
      consistent with a simple nested multilevel model of health care spending.

PMID- 10947580
TI  - The effects of beer taxes on physical child abuse.
AB  - The purpose of this paper is to examine the effects of alcohol regulation on
      physical child abuse. Given the positive relationship between alcohol consumption
      and violence, and the negative relationship between consumption and price, the
      principal hypothesis to be tested is that an increase in the price of alcohol
      will lead to a reduction in the incidence of violence. We also examine the
      effects of illegal drug prices and alcohol availability on the incidence of child
      abuse. Equations are estimated separately for mothers and fathers, and include
      state fixed effects. Results indicate that increases in the beer tax may decrease
      the incidence of violence committed by females but not by males.

PMID- 10947581
TI  - International comparisons of pharmaceutical prices: what do we know, and what
      does it mean?

PMID- 10947582
TI  - The way to win: teach the jury about medicine.

PMID- 10947583
TI  - Don't settle too quickly--I know from experience.

PMID- 10947584
TI  - Could Occam's razor save my patient?

PMID- 10947585
TI  - Osler: the saint of Baltimore.

PMID- 10947586
TI  - Reimbursement policies: do health plans consider quality of care?

PMID- 10947587
TI  - Washington beat.

PMID- 10947588
TI  - Now patients will rate you online.

PMID- 10947589
TI  - Make the most of your staff.

PMID- 10947590
TI  - Want to prevent malpractice suits? Listen up.

PMID- 10947591
TI  - What are they teaching in sex ed these days?

PMID- 10947592
TI  - My fellow doctors hurt my child.

PMID- 10947593
TI  - Why politics--like medicine--is a noble calling.

PMID- 10947594
TI  - How plaintiffs' lawyers pick their targets.

PMID- 10947595
TI  - Management challenges faced by managers of New Zealand long-term care facilities.
AB  - This article reports on a postal survey of 78 long-term care managers in one
      region of New Zealand, of whom 45 (58%) responded. Most long-term care managers
      (73.2%) were middle-aged females holding nursing but not management
      qualifications. Most long-term care facilities (69%) tended to be stand-alone
      facilities providing a single type of care (rest home or continuing care
      hospital). The most prominent issues facing managers were considered to be
      inadequate funding to match the growing costs of providing long-term care and
      occupancy levels. Managers believed that political/regulatory, economic and
      social factors influenced these issues. Despite a turbulent health care
      environment and the challenges facing managers, long-term care managers reported
      they were coping well and valued networking.

PMID- 10947596
TI  - Community nursing and health care in the twenty-first century.
AB  - This article reports on research into the changing role of generalist community
      nurses in Victoria during the 1990's. It provides an analysis of the implications
      of current policy trends and presents an overview of current practice and trends
      in contemporary health care delivery in the community. It discusses a vision for
      community nursing inspired by interviews with generalist community nurses
      throughout Victoria, and offers creative recommendations and strategies that will
      facilitate planning for the personal and professional changes necessary to take
      community services into the twenty-first century.

PMID- 10947597
TI  - An assessment of the effects of casemix funding on hospital utilisation: a
      Northern Territory perspective.
AB  - This article is concerned with the methodological issues of assessing the effects
      of casemix funding on hospital utilisation. Time-series analysis and intervention
      analysis are proposed to ascertain the effects. It was found there had been a
      decline in average length of stay and number of bed-days, an increase in weighted
      separations for teaching and non-teaching hospitals, and no apparent increase of
      costliness in terms of a comprehensive casemix index. No evidence of decline in
      quality of care can be established in terms of readmission rates. The long-term
      effects of casemix funding, and specific issues in terms of the funding model
      used, patients and cost shifting between hospital services and community health
      services, remain to be studied.

PMID- 10947598
TI  - Organ transplant AN-DRGs: modifying the exceptions hierarchy in casemix
      classification.
AB  - The study described in this article sought to develop AN-DRG Version 3
      classification revisions for organ transplantation through statistical analyses
      of recommendations formulated by the Australian Casemix Clinical Committee. Two
      separate analyses of variance were undertaken for AN-DRG Version 2 and for the
      proposed Version 3 AN-DRGs, using average length of stay as the dependent
      variable. The committee made four key recommendations which were accepted and
      incorporated into AN-DRG Versions 3 and 3.1. This article focuses on the
      classification revisions for organ transplantation.

PMID- 10947599
TI  - EQuIP accreditation: feedback from a Sydney teaching hospital.
AB  - The Australian Council on Healthcare Standards' new Evaluation and Quality
      Improvement Program (EQuIP) accreditation model reflects the worldwide trend
      towards incorporating continuous quality improvement and patient-focused care
      goals into hospital/health service accreditation. We conducted a post-EQuIP
      feedback survey among senior clinical and managerial staff at a Sydney teaching
      hospital and identified significant levels of negative feedback among
      respondents. Principal concerns were related to perceptions that the process was
      unnecessarily unwieldy and that it offered little value in terms of patient care
      delivery for the significant amount of human resources it consumed.

PMID- 10947600
TI  - Models of integrated cancer care: a critique of the literature.
AB  - A number of models that integrate care across the hospital-community interface
      have been developed. Consumers and health care providers who are considering
      adopting this approach to service delivery need to consider which model is most
      suitable for implementation in their setting. A comprehensive review of the
      literature was conducted to identify and describe integrated care delivery
      models. This article defines five integrated models of care, provides a critical
      analysis of each model, and evaluates the extent to which claims about the models
      are supported by clinical reports and empirical findings. Finally,
      recommendations are made regarding implementation.

PMID- 10947601
TI  - The organisational context for teamwork: comparing health care and business
      literature.
AB  - Teams are a significant tool for promoting and managing change. There are shared
      definitions of teamwork in the literature, and agreement on general benefits and
      limitations of working in teams. However, the historical development of teamwork
      differs between health care and the business environments of manufacturing and
      service industries. The impact of the organisational context on teamwork appears
      to differ most, when literature from the two environments is compared. As a
      result, there are specific issues that are unique to the development and
      implementation of health care teams. This article summarises the unique team
      structures and the issue of professionalization in health care teams, while
      recommending that team members acknowledge their professional differences and
      focus foremost on meeting patient needs.

PMID- 10947602
TI  - Designing a nationally acceptable system of hospital peer grouping.
AB  - Little has been published on the design, use and evaluation of peer groupings of
      hospitals. This article explores the issue in the context of public hospitals in
      New South Wales. The process, established over the last two years by New South
      Wales Health, aims to meet six principles of peer grouping. Through a six-step
      procedure, the methodology focuses on the classification of hospitals by role,
      size and measure of acuity. Further research is needed to compare benchmarking
      across States and to identify which of the methodologies should be adopted
      nationally.

PMID- 10947603
TI  - Educating health managers: the role of SHAPE.
AB  - This article highlights the need of health professionals to add management skills
      to their portfolio, and discusses the role of SHAPE in meeting this need. A list
      of management-related courses that are available to health professionals is
      provided.

PMID- 10947604
TI  - An ethnography of midwifery work patterns during organisational redesign.
AB  - Despite a substantial increase in midwifery research since the early 1990's,
      there remains a lack of available research into the everyday practice of
      midwives. In general, hospitals are striving to reduce costs and increase
      efficiencies, so many hospital-based midwives are being exposed to hospital
      restructuring processes. The primary purpose of my research was to learn about
      the work patterns of hospital midwives during organisational redesign. A large
      Brisbane hospital, as part of its hospital-wide organisational redesign plan,
      merged two postnatal wards to create a new, larger unit. With this amalgamation,
      the ward midwives were exposed to several service delivery changes. Midwifery
      work patterns during this organisational change revealed a milieu characterised
      by a culture of business. The impact of change introduced ritual and personal
      elements that influenced midwifery work patterns.

PMID- 10947605
TI  - Welfare states for sale: neighbouring countries and the public-private mix.

PMID- 10947606
TI  - Approaches to changing the use of time in a public hospital.
AB  - This article describes a qualitative study that used documentary sources and
      interviews with a cross-section of clinical managers and staff to identify the
      ways in which use of time changed in two clinical units following the
      introduction of casemix-based funding in Victoria. For staff at all levels within
      the hospital system, changes in the use of time were experienced that affected
      both the organisation of work and the care provided. The two units approached the
      management of time in different ways. From the introduction of casemix-based
      funding to the conclusion of this study there were improvements in efficiency in
      both clinical units. The case studies are compared and the consequences of
      different approaches to managing time in clinical units are described.

PMID- 10947608
TI  - First, build the foundations: practical considerations in general practitioner
      mental health service liaison.
AB  - The co-working relationship between general practitioners and local mental health
      services lies at the heart of the success of recent changes in mental health
      care. These changes have seen large-scale deinstitutionalisation, a shift to
      primary and community care, and a government policy of prevention and
      partnerships. This article outlines a liaison project developed jointly by the
      South-East New South Wales Division of General Practice and the Southern Area
      Mental Health Service to address these issues. We describe the development of a
      protocol of basic standards which were practical, pragmatic and possible and,
      when fully established, would be the foundation of effective, efficient and
      efficacious shared care in mental health.

PMID- 10947607
TI  - Characteristics of a rural geriatric rehabilitation service.
AB  - The aim of this article is to examine the role of two geriatric rehabilitation
      units in a large rural area, and compare them with published data about
      rehabilitation units in urban settings. We look at the inputs to the units and
      the measurable outputs, including length of stay, discharge disposition of
      patients and changes in patient activities of daily living. We show that
      rehabilitation services provided in the rural environment have lengths of stay
      and improvements in activities of daily living that are similar to those found in
      urban areas.

PMID- 10947609
TI  - The beginning of a structural reform: reorganising the front line of a mental
      health service.
AB  - National and State priorities for mental health services have directed emphasis
      towards early intervention and prevention. One of the key priorities is to ensure
      that entry to mental health services is efficient, effective and accountable.
      This study describes the process of restructuring the front line of a large and
      complex mental health service. Adopting the total quality management approach,
      all stakeholders in the service collaboratively developed a single set of
      protocols and guidelines to achieve standardisation of documentation, assessment
      of risks and urgency, and to improve the overall quality of the service.

PMID- 10947610
TI  - Availability and accessibility of evidence-based information resources provided
      by medical libraries in Australia.
AB  - This article reports on the results of an exploratory survey of the availability
      and accessibility of evidence-based information resources provided by medical
      libraries in Australia. Although barriers impede access to evidence-based
      information for hospital clinicians, the survey revealed that Medline and Cinahl
      are available in over 90% of facilities. In most cases they are widely accessible
      via internal networks and the Internet. The Cochrane Library is available in 69%
      of cases. The Internet is widely accessible and most libraries provide access to
      some full-text, electronic journals. Strategies for overcoming restrictions and
      integrating information resources with clinical workflow are being pursued.
      State, regional and national public and private consortia are developing
      agreements utilising on-line technology. These could produce cost savings and
      more equitable access to a greater range of evidence-based resources.

PMID- 10947611
TI  - Corporate governance of public health services: lessons from New Zealand for the
      state sector.
AB  - New Zealand public hospitals and related services were grouped into 23 Crown
      Health Enterprises and registered as companies in 1993. Integral to this change
      was the introduction of corporate governance. New directors, largely from the
      business sector, were appointed to govern these organisations as efficient and
      effective businesses. This article presents the results of a survey of directors
      of New Zealand publicly-owned health provider organisations. Although directors
      thought they performed well in business systems development, they acknowledged
      their shortcomings in meeting government expectations in respect to financial
      performance and social responsibility. Changes in public health sector provider
      performance indicators have resulted in a mixed report card for the sector six
      years after corporate governance was instituted.

PMID- 10947612
TI  - The role of the Advanced Casualty Management Team in St John Ambulance Australia
      (New South Wales District).
AB  - St John Ambulance is a household name synonymous with the teaching and provision
      of first aid. Recently the organisation has developed pre-hospital emergency care
      services through the introduction of the St John Ambulance Australia Advanced
      Casualty Management Team in New South Wales. The Advanced Casualty Management
      Team represents a move away from the practice of first aid by lay personnel and
      is a natural extension of the traditional work and principles of St John
      Ambulance. This article provides an overview of the Advanced Casualty Management
      Team and discusses its contribution to pre-hospital trauma care delivery.

PMID- 10947613
TI  - ASP model could bring PACS technology to the masses.

PMID- 10947614
TI  - Low-dose CT. The promise and the paradox of lung cancer screening.

PMID- 10947616
TI  - Gene therapy lays the foundation for radiology's next frontier.

PMID- 10947615
TI  - Interventionalists take on new role in pain management.

PMID- 10947617
TI  - X-ray, coincidence data merge in functional anatomic mapping.

PMID- 10947618
TI  - Quality of processed blood for autotransfusion.
AB  - Centrifugal red blood cell washers for intraoperative autotransfusion process
      shed blood during surgery. In this study, the quality of processed fresh, human
      bank blood was assessed in a standardized laboratory setting during standard,
      medium, and high flow processing. Red cell recovery rates and plasma washout
      efficiencies were compared using three different devices. The accurate parameters
      measuring effectiveness and product quality were red cell mass (RCM) flow rate
      and the plasma washout efficiency. Cobe BRAT 2, a system with discontinuous flow
      (DF) and a cylindrical centrifuge bowl, permitted processing in standard and
      medium flow of 26 and 35 mL RCM/min, respectively, with washout of residual
      plasma albumin of 93.2 and 91.2%. The Medtronic Sequestra 1000, a DF system with
      a conical centrifuge bowl processed blood at 15 and 23 mL RCM/min and eliminated
      plasma albumin with 98.4 and 96.8% washout during standard and medium flow,
      respectively, with significant red cell loss occurring during medium flow. The
      respective speeds of high-flow programs with BRAT 2 and Sequestra 1000 were 15
      and 22 mL RCM/min, related to a hematocrit in the holding bag, less than that of
      the incoming blood from the reservoir. Washout was 58.2 and 58.3%, respectively.
      Fresenius CATS, a continuous flow (CF) device, produced flow rates of 19, 24, and
      43 mL RCM/min and plasma albumin elimination of 97.8, 94.4, and 93.3% in
      standard, medium, and high-flow, respectively. Holding bag hematocrits with CF
      exceeded that of DF. Standard, medium, and high-flow programs of CATS may be used
      without restriction.

PMID- 10947620
TI  - CDI Blood Parameter Monitoring System 500--a new tool for the clinical
      perfusionist.
AB  - Sarns/3M Health Care has recently introduced the CDI 500 Blood Parameter
      Monitoring System. In addition to parameters previously available, this system
      now offers continuous monitoring of the patient's oxygen consumption (VO2/min)
      and potassium concentration ([K+]). The purpose of this study was: (1) to compare
      the [K+] from the CDI 500 with the [K+] derived from our hospital's laboratory;
      and (2) to compare the VO2/min from the CDI 500 with the results obtained
      utilizing the "gold-standard" Fick equation. The mean absolute difference in [K+]
      was 0.10 mEq/L with a mean percentage error of only 3.93%. The mean absolute
      difference in VO2/min was 18.78 ml O2/min, with a mean percentage error of
      11.63%. We concluded that the [K+] correlated well and that 9.13% of the oxygen
      consumption percentage error was attributable to the exclusion of dissolved
      oxygen in the calculation used by the CDI 500, with the remaining 2.5%
      attributable to differences in technology. We recommended that future upgrades to
      the CDI 500 should include dissolved O2 when measuring oxygen consumption and
      consideration should be given to increasing the operating range for [K+].

PMID- 10947619
TI  - Effect of autotransfusion on fibrinolysis in open heart patients.
AB  - Autotransfused blood is often used as an alternative to banked blood. The
      fibrinolytic consequences of autotransfused blood are undefined. This prospective
      study was designed to determine the effect of intraoperative autotransfused blood
      on fibrinolysis and other coagulation parameters. Ten consecutive patients
      undergoing cardiopulmonary bypass (CPB) for open-heart procedures were studied.
      All patients received autotransfused blood intraoperatively and tolerated the
      procedure. Blood samples were taken preoperatively, intraoperatively, and at 6,
      12, and 24 hours postoperatively. Coagulation parameters including prothrombin
      time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin degradation
      products, and D-dimer levels were measured at each time point. In addition, the
      quantity of autotransfused blood and additional standard blood products were
      recorded. Nonparametric repeated measures analyses with post hoc tests adjusted
      using the Bonferroni correction were used to analyze the data. Mean PT increased
      from 13.9 +/- 3.0 seconds preoperatively to 15.7 +/- 1.6 seconds
      intraoperatively, but then gradually declined to 14.5 +/- 1.1 seconds 24 hours
      postoperatively. A similar temporal pattern was observed for PTT, which reached a
      peak of 55.7 +/- 33.0 seconds intraoperatively from a preoperative baseline of
      44.0 +/- 15.3 seconds. Adjusted post hoc comparisons of fibrinogen levels
      indicated a statistically significant difference between preoperative and 6 hour
      postoperative medians, (p < .0083). Fibrin degradation products had a modest and
      nonsignificant decrease over the 24-hour study period, (from 12.6 +/- 6.7 mcg/mL
      preoperatively to 9.0 +/- 1.6 mcg/ml 24 hours postoperatively), while D-dimer
      levels rose from a baseline of 0.54 +/- 0.09 mcg/mL to 0.98 +/- 0.48 mcg/mL 6
      hours postoperatively, but declined nearly to baseline by 24 hours
      postoperatively, (0.62 +/- 0.11 mcg/mL). We conclude that although autotransfused
      blood may activate the fibrinolytic pathway, its use remains safe and does not
      require the use of additional banked blood products.

PMID- 10947622
TI  - Myocardial protection: an overview.
AB  - The goals of myocardial protection during cardiac surgery are not only to
      facilitate the operation by providing a quiet bloodless field, thereby
      facilitating the precision of the operation, but also to avoid iatrogenic injury
      induced by cardiopulmonary bypass itself or by surgically imposed ischemia. In
      addition, myocardial protective strategies are geared to preventing reperfusion
      injury upon resolution of the coronary occlusion and the ultimate release of the
      aortic cross clamp. Cardioplegia plays a very important role in myocardial
      protection strategies. Acting as a selective perfusion agent, cardioplegia
      solutions can alter or inhibit ischemic injury by virtue of hypothermia and
      asystole. In addition, cardioplegia can be used to avoid reperfusion injury by
      altering the conditions of its delivery and the composition of the solution using
      various adjunctive agents and pharmacologic therapies for which cardioplegia
      solutions serve as a vector. Future strategies, particularly for off-pump
      surgical procedures, may incorporate systemic delivery of therapeutic agents to
      the heart directly either in conjunction with or without cardioplegia.

PMID- 10947621
TI  - In vitro evaluation of the Medtronic cardioplegia safety system.
AB  - Myocardial preservation demands the precise and accurate delivery of cardioplegic
      solutions to provide nutritive delivery and metabolic waste removal. The purpose
      of this study was to evaluate the performance characteristics of the Medtronic
      CSS Cardioplegia Safety System in an in vitro setting. The CSS was evaluated
      under the following conditions: blood to crystalloid ratios of 1:0, 1:1, 4:1,
      8:1, 0:1; potassium concentrations of 10, 20, and 40 mEq L-1; volumetric delivery
      collection at 100, 250, 500, 750, and 990 mL/min; pressure accuracy at 100 and
      300 mmHg; and system safety mechanisms. Measured and predicted values from the
      CSS were compared using one way ANOVA, with statistical significance accepted at
      p < or = 0.05. The measured values for the tested ratios and volume collections
      were all within the manufacturer's technical parameters. Potassium concentration
      results were all within expected values except at 100 mL/min, where the measured
      value of 17.1 +/- 2.1 mmol was lower than the expected 20.0 +/- 0.2 mmol (p <
      .034). As flow rates changed, the CSS line pressure error was constant (0.5 to
      3.7%), and the only significant difference was observed at 100 mmHg, 500 mL/min
      (102.3 +/- 1.7 vs. 100.0 +/- 0.0 mmHg, P < .003). The device performed accurately
      and reliably under all simulated safety conditions, including bubble detection,
      over pressurization and battery backup. In conclusion, the performance of the CSS
      was within the manufacturer's specifications for the majority of the tested
      conditions and operated safely when challenged under varying conditions.

PMID- 10947623
TI  - Factors affecting perfusionists' decisions on equipment utilization: results of a
      United States survey.
AB  - The decision to utilize extracorporeal equipment is influenced by a number of
      factors, including clinical efficacy, cost effectiveness, and personal judgment.
      The purpose of this study was to report the results of a national survey that
      examined factors affecting perfusionists' decisions on equipment utilization. An
      80-question survey was mailed to chief perfusionists at 1030 U.S. hospitals
      performing open-heart surgery. 524 completed surveys were returned, which
      represented 797 hospitals (78.8%) and 671,290 procedures over a 2-year period
      (July 1996-June 1998). Within the survey, 36 questions pertained to equipment
      utilization and served as the basis for this report. The perfusion equipment that
      had seen the greatest reduction in use were; heparin-coated circuits (HCC)
      (12.0%), in-line blood gas monitors (9.7%), soft-shell venous reservoirs (SSVR)
      (7.2%), and in-line arterial hemoglobin monitors (6.3%). Cost was the major
      determinant affecting the decision for the following devices: in-line blood gas
      monitors (82.4%), cardioplegia in-line delivery filters (75.0%), in-line arterial
      hemoglobin monitors (69.7%), HCC (55.6%), and SSVR (43.2). Ineffectiveness was
      the major reason reported for discontinuation of arterial-line bubble traps
      (64.7%), venous reservoir level detectors (50.0%), and arterial-line pressure
      manometers with pump shutdown (50.0%). 438 respondents discontinued use of one or
      more of 29 different devices during the past 2 years. Cost was the major reason
      in 52.7% of the cases, ineffectiveness in 33.1%, and 14.2% were in a category
      labeled "other." The pressures brought upon by the changing healthcare structure
      have influenced perfusionists' equipment selection, with cost being a major
      factor affecting clinical decisions for certain device utilization.

PMID- 10947624
TI  - Evaluation of a "heads-up" display for cardiopulmonary bypass.
AB  - Multiple variables must be analyzed during cardiopulmonary bypass in order to
      judge the adequacy of perfusion. Variables when viewed singly can be confusing
      and lead to inaccurate representation of the physiological status of the patient.
      Communication between the perfusionist and members of the surgical team requires
      accuracy and complete presentation of pertinent data. Toward this goal of
      improving the assimilation and processing of information during cardiopulmonary
      bypass, a multivariable computer-aided "Heads-up Display" (HUD) was developed.
      Modern jet pilots use heads-up display for rapid assimilation of information when
      making judgments about the performance of their aircraft and weapons systems.
      Heads-up display is an electronically generated display that is superimposed upon
      a pilot's forward field of view. An analogy between a jet pilot and a
      perfusionist can be made. A geometric form, a hexagon, is used as part of the
      heads-up display for cardiopulmonary bypass (CPB-HUD). The polygon represents a
      performance evaluation graph. Each of the six "spokes of a wheel" represents a
      physiological parameter. The represented variables are: cardiac index, peripheral
      vascular resistance, hematocrit, dynamic operating blood level, venous
      saturation, and mean arterial pressure. The perfusionist inputs target values.
      Target values are then compared to actual values and expressed as a percentage.
      If all targeted values are achieved, the graphical representation is a hexagon.
      The surgical team rapidly recognizes abnormal patterns that are outside
      individual target values. They include, but are not limited to, patterns of:
      vasoconstriction, vasodilatation, hypovolemia, decreased oxygen carrying
      capacity, and several others. The CPB-HUD has proved to be of value for planning,
      real time evaluation, retrospective analysis of cardiopulmonary bypass benchmark
      data, and as an aid in the teaching of new personnel concerned with
      cardiopulmonary bypass.

PMID- 10947625
TI  - Electrostatic forces on the surface of metals as measured by atomic force
      microscopy.
AB  - Electrostatic forces play an important role in modulating the interaction of
      plasma proteins and blood cellular components with the surface of the vascular
      endothelium. Based on the concept that electrostatic forces residing on the
      surface of metal intravascular prostheses, such as the stent, also are critical
      in influencing blood interactions with those surfaces and the vascular wall,
      these studies were designed to measure these forces on 4 metals using atomic
      force microscopy (AFM). AFM measurements performed in a low saline aqueous medium
      at physiological pH indicate a similar net electronegative surface charge level
      for gold and 316l stainless steel that is significantly higher than the level
      measured on an electropolished Nitinol surface. Heat oxidation of the Nitinol
      surface increased the overall electronegativity and created a more homogeneous
      surface charge distribution. This study demonstrates that AFM force measurements
      can be a valuable approach to understanding the electrostatic surface of metallic
      as well as other biomaterials that may be important in understanding how these
      surfaces influence vascular healing at intravascular interventional sites.

PMID- 10947626
TI  - Protein interactions with endovascular prosthetic surfaces.
AB  - Blood protein interaction with prosthetic surfaces seems to be the initial step
      in the chain of events leading to tissue incorporation of endovascular devices.
      This paper focuses on the relationship between surface free energy and protein
      adsorption on metals and polymers commonly used for fabricating vascular
      prosthetic devices. Our results support a relationship between surface energy and
      protein adsorption. Albumin was more easily eluted than fibrinogen and
      fibronectin from most metals and all polymeric surfaces considered. Following
      elution, metals retained a larger fraction of protein as compared to polymers.

PMID- 10947627
TI  - Influence of topography on endothelialization of stents: clues for new designs.
AB  - To evaluate the influence of stent design on endothelialization of the stented
      surface, we placed trapezoidal objects of variable thickness on a confluent
      culture of endothelial cells and subjected the assembly to flow and shear
      conditions similar to those found in arteries. After 24 h, we measured and
      analyzed the area on top of the objects covered by cells and the maximum
      migration distance from the borders. In addition, we evaluated areas devoid of
      cells surrounding the objects, which developed after exposure of the assembly to
      flow. The cell-covered area and migration distance significantly decreased on
      objects 75 microns thick, and it was nonexistent on objects 250 microns thick.
      Areas devoid of cells or gaps were largest adjacent to the downflow side of the
      object, disposed transversely to flow. Cell gaps were smallest along the side
      aligned with flow. In conclusion, endothelial cell coverage may be impaired by
      stent wall thickness larger than 75 microns. It is likely that this impairment is
      related to flow disturbances impairing cell attachment.

PMID- 10947628
TI  - Heparin-coated stents.
AB  - Stenting has revolutionized the field of interventional cardiology. However,
      early studies revealed a high incidence of thrombotic occlusion of the stent and
      significant bleeding complications resulting from the use of intensive
      anticoagulation after implantation. One of the strategies used to reduce stent
      thrombosis and hemorrhagic complications has been to decrease the thrombogenicity
      of the stent surface. For this purpose, a unique heparin surface patented by
      Carmeda AB (Stockholm, Sweden)--the Carmeda BioActive Surface (CBAS)--has been
      coated onto Cordis (Johnson & Johnson) stents. Preclinical evaluations of the
      thromboresistance of heparin-coated stents and clinical studies of heparin-coated
      stents in a variety of clinical settings are discussed.

PMID- 10947629
TI  - Stent-based gene therapy.
AB  - Delivery of gene therapy to inhibit intimal hyperplasia has been proposed to
      prevent postangioplasty restenosis. We sought to apply gene therapy by using a
      stent-based technique. There are several hurdles that must be overcome before
      gene-stent therapy can be applied successfully in clinical trials. These include
      increasing the efficiency of gene delivery through atherosclerotic plaque;
      increasing intramural retention times; preventing the inflammatory reaction that
      stents coated with biodegradable polymers can elicit; overcoming the risk of
      systemic gene delivery; and accessing the adventitia via percutaneous approach.
      We evaluated a gene-stent delivery mechanism based on microporous metal
      microneedles developed with nanotechnology in an attempt to overcome some of
      these problems. A novel approach to the transfection of genes by microfabricated
      technology was evaluated in smooth muscle cells in culture. We demonstrated that
      microneedles can deliver gene therapy to smooth muscle cells in culture and can
      produce controlled penetration of the IEL and intima. We conclude that taller
      microneedles need to be developed to reach the media in diseased human arteries
      and that this technology has the potential to be incorporated in a stent to
      deliver gene therapy in atherosclerotic plaque.

PMID- 10947630
TI  - Blood flow and thrombus formation determine the development of stent neointima.
AB  - To establish a relationship between flow, acute thrombus formation, and late
      intimal formation in implanted arterial stents, canine femoral arteries with
      normal blood flow were compared to contralateral femoral arteries with restricted
      blood flow. Thrombocyte activity over the stent segment was evaluated for 3 h
      after stent placement with nuclear scanning, following administration of In-111
      labeled platelets. To evaluate long-term stent patency in relationship to
      arterial flow, an additional group of dogs were subjected to long-term
      observation. Matched, symmetrically implanted femoral stents with normal and
      restricted flow were explanted at 1, 12, and 24 weeks for histological analysis
      and comparative measurement of neointimal thickness. Angiographic studies were
      performed before and after nuclear scan in the acute animals and before explant
      in the chronic animals. Acutely, heparinization prevented subocclusive or
      occlusive thrombus, regardless of flow. In the absence of heparinization, normal
      arterial blood flow did not prevent thrombus formation on stents. Chronically,
      stents with flow restriction had significantly greater neointimal formation in
      comparison with unrestricted stents. Histological studies suggested that the
      stent neointima resulted from progressive replacement of stent thrombus.

PMID- 10947631
TI  - Endovascular stents: update on stents in practice.
AB  - Endovascular stent use has expanded at an unprecedented rate; they are currently
      being used in more than 50% of coronary angioplasty procedures. This rapid
      acceptance is due to excellent in-hospital results coupled with improved long
      term clinical endpoints from small randomized trials, which have investigated
      only a few stent designs in small patient subsets. The generalized use of stents
      in all lesions has yet to be substantiated. Current limitations of stents include
      the occurrence of subacute thrombosis, late neointima proliferation, and design
      issues such as stent visibility and deliverability. New designs, including stent
      coatings and stents for bifurcations, will increase the use of stents for
      endovascular procedures.

PMID- 10947632
TI  - Endothelial cell seeding on prosthetic surfaces.
AB  - Once thought to be a monolayer of passive cells lining the vasculature,
      endothelial cells are now known to be important regulators of normal vascular
      physiology. Unfortunately, these critically important cells are destroyed or
      removed by interventional and surgical procedures performed to recanalize or
      bypass vascular obstructions. The loss of these cells contributes to thrombosis
      and restenosis, the major complications observed after angioplasty, stent
      deployment, and prosthetic graft implantation. One approach to preventing these
      complications is the placement of endothelial cells on stents or prosthetic
      grafts prior to their placement in vivo in the hope that these cells will, after
      growth and maturation, release the factors necessary to inhibit thrombosis and
      intimal thickening. The purpose of this review paper is to provide an overview of
      the physiologic functions of normal and dysfunctional endothelial cells, and to
      discuss experiments in which endothelial cells have been placed on metallic
      stents and prosthetic grafts.

PMID- 10947633
TI  - Endothelial cell migration onto metal stent surfaces under static and flow
      conditions.
AB  - Restenosis associated with intimal hyperplasia and thrombosis at sites of balloon
      angioplasty or stent placement remains an important clinical problem. It is
      likely that loss or damage to the arterial endothelium associated with these
      interventional procedures as well as the rate of its restoration plays a critical
      role in the extent of restenosis. Migration of arterial endothelial cells from
      adjacent intact endothelium is the predominant source of cells involved in re
      endothelialization of the injured site. In this paper, we review the influence of
      hemodynamics on endothelial cell migration, both in vivo and in vitro. In
      addition, we present recent in vitro studies demonstrating the importance of the
      nature of metal substrates in modulating endothelial cell migration rate.
      Finally, we review the cellular and molecular mechanisms likely involved in
      governing endothelial cell migration, and relate them to a possible scenario of
      endothelial response to injury at sites of arterial intervention. Understanding
      the important factors regulating endothelial migration may provide insights that
      will ultimately lead to methods to accelerate endothelial healing and reduce the
      occurrence of arterial restenosis.

PMID- 10947634
TI  - The Oasis Spa: rethinking our support to people with serious mental illness.
AB  - A key component to be addressed when developing programs is quality of life. This
      article describes the rationale, design, and implementation of the Oasis Spa at
      the Centre for Addiction and Mental Health in Toronto. This initiative was
      generated from an acknowledgement and awareness of the full range of supports-
      biological, social, emotional, and spiritual--which all people need to live their
      lives fully. The ambiance and services created as a result of consumer feedback
      are typical of any spa found in the community that provides self-care, nurturing,
      comfort, and retreat. The Oasis provides a full range of holistic health
      strategies which empower clients to take an active role in their recovery.
      Society is becoming more aware of the mainstream trend towards integrative
      medicine; however, this service appears to be unique in mental health.
      Approaching the third millennium, it is imperative that society develops a less
      polarized approach to health care.

PMID- 10947635
TI  - [Splendor and misery in the local organization of mental health: a look at the
      field].
AB  - Collaboration among public and community resources (or concentration as it is
      referred to in French) is a practice much favoured by governments for ideological
      and economic reasons. But if administrative collaboration is relatively easy to
      set up, what about collaboration among front-line field workers? What are the
      ingredients likely to engender true collaboration among practitioners, and what
      obstacles do they meet with on a practical day-to-day level? Experience acquired
      in the West Island area of greater Montreal has led us to the conclusion that
      many issues need to be examined and understood: the difficulty of reconciling
      client empowerment with treatment; the difficulty of harmonizing the values and
      convictions prevailing in institutional and community-based networks; the
      tendency for practitioners to keep clienteles for themselves within a treatment
      environment. Despite these difficulties, it is evident that there will be a trend
      towards increasing collaboration where clienteles are growing and where problems
      are becoming more complex.

PMID- 10947636
TI  - Independent living centres: an innovation with mental health implications?
AB  - The findings of a national study of Independent Living Centres (ILCs) in Canada
      suggest that the ILCs are a potentially powerful innovation for the
      consumer/survivor movement. Independent Living Centres are non-profit, cross
      disability, consumer-driven, community-based centres which promote both
      individual empowerment and community change. The IL and mental health reform
      paradigms share in the development of empowerment theory, acknowledge the
      importance of consumer driven organizations, and utilize a socio-political
      analysis of disability which goes beyond the person and recognizes the
      environment as problematic. Accordingly, the reform paradigm seeks innovative
      services which are separate from the traditional mental health system. Before
      this can fully become a reality, mental health professionals need to increase
      their knowledge of the IL philosophy and ILC practice. Similarly, ILCs need to
      increase their knowledge of consumer/survivor empowerment and recovery and
      carefully assess any barriers that exist in terms of consumers/survivors
      accessing the ILCs. Collaboration between the IL movement and mental health will
      increase the likelihood of ILCs becoming a stronger resource for
      consumers/survivors.

PMID- 10947637
TI  - A multi-year evaluation of a parent support centre.
AB  - This paper summarizes the results of a multi-year evaluation of a parent support
      centre project. Qualitative data gathered both from a series of individual
      interviews with participants and from a series of focus-group interviews with
      both participants and workers are presented. The developmental process of the
      project is detailed. Positive outcomes with regard to individual changes in
      social support, parenting, and self-esteem are described. The accomplishments of
      the project's goals regarding participant satisfaction with activities and
      programs and the development of indigenous leadership are noted; however, the
      project was deemed less successful with regard to ongoing recruitment of
      participants. Implications for practice are discussed.

PMID- 10947638
TI  - Safe beds: the new partner in Niagara's crisis system.
AB  - Over the past few years and for a variety or reasons, consumers/survivors in the
      Niagara Region have indicated that an alternative to hospitalization is needed.
      This paper describes the community-development process which led to the creation
      of a crisis-response system consisting of Community Crisis Care (CCC) and a Safe
      Beds program operated by the Canadian Mental Health Association St. Catharines
      and District. The system is described, as well as the partnerships that are
      critical to the program's success. Evaluative data are presented along with a
      discussion of critical learnings. Future considerations for program improvement
      also are discussed.

PMID- 10947639
TI  - Organizational change towards the empowerment-community integration paradigm in
      community mental health.
AB  - As a part of a larger study of change towards the values of an empowerment
      community integration paradigm in community mental health, we examined changes in
      3 mental health organizations in 1 community. Using qualitative methods, we
      focused on: (a) change pathways, (b) organizational change outcomes, and (c) the
      factors which helped and hindered change outcomes. We found evidence of a
      paradigm shift in the values and related practices within the organizations. Our
      results and themes are discussed and aimed at understanding and integrating
      knowledge about organizational change and the empowerment-community integration
      paradigm in community mental health.

PMID- 10947640
TI  - [The ODEC (Organization for Development and Community Networks) and mental
      health: from networking to opening in the local community].
AB  - The Organisme de developpement et d'entraide communautaire (ODEC) is a nonprofit
      mental health organization that was established in 1987 and offers mutual help
      and community development services in the Vallee-de-la-Lievre region in the
      Outaouais area of Quebec. Starting with an individual accompaniment service for
      people living with mental health problems, ODEC has succeeded in establishing a
      significant mutual help network that now involves more than 100 people. This
      article comes out of an in-depth case study of ODEC. By analysing the major
      parameters of its journey over more than 10 years, it brings to the fore the
      impact in the mental health field of providing a network in close association
      with community involvement.

PMID- 10947641
TI  - Voices, Opportunities & Choices Employment Club: transforming sheltered workshops
      using an affirmative business approach. The VOCEC Board of Directors.
AB  - Voices, Opportunities & Choices Employment Club (VOCEC) is a non-profit
      "umbrella" corporation that facilitates the development of affirmative businesses
      to create jobs for consumers of mental health services. To date, 5 independent
      businesses have been developed by transforming the resources of sheltered
      workshops within Kingston Psychiatric Hospital and 2 businesses have been
      established in collaboration with a local public library. This paper provides a
      description of VOCEC, including an overview of the affirmative business approach,
      the structure of the organization, and the process of business development.
      Personal reflections provide insights into the experiences of consumers, staff,
      and Board members associated with the corporation.

PMID- 10947642
TI  - [The MRC (County Regional Municipality) team: new configuration of the team and
      mental health reform].
AB  - The concept of the equipe MRC (county regional municipality team) has developed
      as a result of the rapid transformation of mental health services. In most
      regions of Quebec, there has been a transition from an institutional model, where
      all services were provided by a single establishment, to a dispersed model where
      there are a whole range of services provided by a multitude of agencies. In this
      context, partnership becomes a necessity. The intention of the equipe MRC is thus
      to provide a structure that brings together under the same aegis all the public
      sector and community-based personnel working with clients who suffer from severe
      and persistent mental health problems. This article seeks to define the concept
      of the equipe MRC and to assess the state of collaboration among the members of
      these teams, taking into account the fact that relations between community-based
      and public-sector agencies have not always been productive.

PMID- 10947643
TI  - A prototype design of cardiological computerized nursing care plans for an
      electronic patient care record.
AB  - The purpose of this paper is to describe the design and the process of
      Cardiological Nursing Care Plans proposed to be used within an electronic patient
      record that can fulfill both nursing science and experience. The project is
      focused on the development of a clinical database capable of analysis to link
      control of nursing process with clinical outcome.

PMID- 10947644
TI  - The MuPSi project--a learning environment for multiprofessional collaboration.
AB  - Students studying for different professions within the field of health care need
      to practice both multiprofessional collaboration and use of HIS and EPR software.
      The MuPSi concept utilizes computer-mediated communication to provide students
      access to a EPR software to enable the students to act collaboratively as members
      of a virtual health care team. The students are given a fictive patient case and
      use the EPR software to plan and document the care they provide. In order to
      achieve a higher grade of authenticity the case is presented as segments--the
      teachers direct the simulation by recording events that change the situation into
      the patient record.

PMID- 10947645
TI  - General or specific--the Internet pandemonium.

PMID- 10947646
TI  - Computerised coordinated care system in the RISE project.
AB  - It is a fact that elderly peoples' life is characterized by problems such as
      deteriorating health and physical condition, feelings of loneliness, isolation,
      and of being dependent on others, in many aspects of their everyday lives. The
      objective of the RISE project is to provide an efficient vehicle for Health Care
      Professionals for improving Health Care, quality of life and integration of the
      elderly and disabled people with society by implementing Information technology
      applications. In particular, RISE project aims in developing a distributed
      network of service providers across the European Union, which will provide
      integrated types of services to the elderly and disabled population. The purpose
      of this paper is to present the impact of this project concerning the Health
      Informatics sector. It will describe the issues regarding, the needs for
      education and training of the professionals that arise by the introduction of
      this concept, and, the possible ways that such a concept forms an efficient
      vehicle for Health Professionals in assisting these particular groups of users.
      The longer perspective seeks to redefine and reshape the Health Care services'
      larger purpose, i.e. to make those comport with elementary individual needs of
      the elderly and disabled by introducing new methods of efficient health service
      provision. To achieve this there is an increased need for the training of the
      professionals. The outcome of RISE will be a set of specialised software
      components, tools and training methodologies designed to assist the Health
      Professionals achieving the aforementioned tasks.

PMID- 10947647
TI  - Information dissemination and training: two key issues for consolidating and
      strengthening the results of health telematic projects.
AB  - The concepts expressed in this paper concerns the activities to be developed
      within HEALTHLINE, a European project under the Telematics Application programme.
      HEALTHLINE is an umbrella project which takes initiatives and provides links to
      other international projects on health telematics. The projects involved are
      NIVEMES and RISE; they represent the starting point from which a common approach
      will be developed. The experience gained from these projects has highlighted two
      emerging requirements: information dissemination and training. To fulfil the
      needs of information, an Internet corner will be set up; it will allow citizens
      and health professionals to find and exchange information as well as to discuss
      themes concerning health care. Due to the most advanced technologies recently
      introduced, the Health care sector has had to modify its traditional ways of
      working to aid professionals in exploiting new training techniques and Health
      Care provision methods. HEALTHLINE will focus on training and on the development
      of the use of new tools and services. Furthermore, the project will exploit the
      training methodologies based on multimedia technology for developing training-on
      the-job modules. The entire system, in its final stage, will consist of a network
      for co-operating training and information dissemination; European sites in the
      project will share information, training material and provide education and
      information on tele-health, medical and health-care issues to health care
      providers, beneficiaries and the general public.

PMID- 10947648
TI  - Development of a contextual computer-based nursing simulation.
AB  - This paper will present a brief review of the use of simulations in clinical
      reasoning research and education, followed by a case-study describing the
      development of a research tool which attempted to elicit the decision-making
      strategies of novice and competent hospital nurses. The central feature of this
      simulation was the degree of flexibility and control it gave to the nurse
      participants over their information seeking strategies. The ability of this
      interactive multimedia simulation to mimic a real ward environment has a great
      potential in the teaching of clinical reasoning skills to health professionals.

PMID- 10947649
TI  - Problem-based education and health informatics.
AB  - In this contribution the traditional approach to education is presented and
      compared with the problem-based approach. Trends in the healthcare system
      indicate that education in health informatics and training in ICT becomes
      mandatory for students and healthcare professionals. These trends are presented.
      In addition the role of ICT in education and training is discussed. Finally some
      educational programs are presented.

PMID- 10947650
TI  - Simulation model for educating the general public for the AIDS epidemic.
AB  - In the Health field, there is an increasing need to give the Health professional
      the opportunity to experiment on real situations without necessarily having to be
      in contact with the patient. In order for this to be achieved, there must be a
      virtual reality representation via a safe and user friendly system, such as a
      computer. This means that by using Simulation and modelling techniques new models
      have to be constructed which will portray the reality. The scope of this paper is
      to present a Simulation Model and Practical for Educating the General Public for
      the AIDS Epidemic. The model and the practical were developed by using the tools
      and applications created under the COAST project.

PMID- 10947651
TI  - Analysis, modelling and simulation of information systems as part of the medical
      informatics program at Heidelberg/Heilbronn.

PMID- 10947652
TI  - GALEN-IN-USE: application in Greek and influences on education.
AB  - GALEN-IN-USE is a European project that aims to promote greater European
      harmonization and to overcome the problems encountered in using traditional
      coding and classification systems. This paper presents the work done by the Greek
      Centre of Medical Informatics and Terminology, as a collaborating centre of GALEN
      IN-USE(GIU), in order to apply GIU's tools to Greek Health Care System as well as
      the affect of this application in education.

PMID- 10947653
TI  - A framework for the creation of user-oriented medical textbooks on the World-Wide
      Web.
AB  - The use of the World Wide Web as a medium for the dissemination of course
      textbooks has proved to be effective both pedagogically and in terms of cost.
      However, there are some limitations inherent in this approach. In this paper we
      discuss the issues involved in the production of network accessible textbooks and
      present a framework which attempts to address the limitations of existing schemes
      through the use of a view-filter mechanism. We describe our proposal from a
      conceptual viewpoint and then discuss its applicability through the presentation
      of a prototype system. Finally, conclusions are drawn and future plans discussed.

PMID- 10947654
TI  - The "MICTRID" concept in the educational offer for medical informatics and
      telemedicine at the Politecnico di Milano.
AB  - Research and training programs in Medical Informatics and Telemedicine offered at
      the Politecnico di Milano are summarized. The educational pathways refer to the
      programs of the 5-years based Laurea Degree, the 3-years based Diploma
      Universitario Degree, of the post-Laurea 3-years-based Doctoral Degree and of the
      1-year based Master Degree, as well as of the Continuing Education Program. The
      Research programs focus on databases and extend to the optimisation of the
      "Visible Human Dataset--Milano Mirror Site" services. Additional activities
      relate to standardization at both Italian and European levels and to cooperations
      with hospitals and manufacturers.

PMID- 10947655
TI  - Educating nurse practitioners as primary health care providers via distance
      learning using the World Wide Web.

PMID- 10947656
TI  - Health telematics in postgraduate study.
AB  - The paper presents a description of a system that exploits possibilities offered
      by WWW and assists postgraduate education of physicians preparing for
      examinations in their medical specialisation. The system, which is a modification
      of the educational oncological system ONCOL1 designed earlier by the authors, is
      constructed so as to operate within the Polish medical education structure.

PMID- 10947657
TI  - Health telematics training network (HEALTHNET).

PMID- 10947658
TI  - The process of implementation.
AB  - After the selection of an information system (either a HIS or a NIS) the process
      of implementation is of vital importance to get the system up and running. This
      paper describes how an implementation process can be prepared and in which way
      skillful implementation can contribute intensively to the pleasure of right use
      of the system. The author has carried the final responsibility of very different
      implementation processes for about 10 years in a quite a number of hospitals.
      Based on this experience success factors and pitfalls are given. The paper
      addresses in the first place hospital- and nursing managers and is written to
      stimulate professional implementation. A process that can cause real pleasure and
      fine results when it is carried out on the right way.

PMID- 10947659
TI  - The process of charging medical tests, drugs and materials in an integrated
      H.I.S.: problems and challenges.
AB  - The purpose of this paper is to present in brief the billing procedures related
      to Medical Tests, drugs and supplies in H.I.S. and to discuss the problems and
      the challenges to the user.

PMID- 10947660
TI  - Security of electronic patient record and education.
AB  - The evolution of the paper-based to Computer-based Patient Records (CPR) or
      Electronic Patient Records (EPR) changes the way in which we have to perceive and
      deal with privacy and security issues. The education and awareness of the users
      and public of the selfsame issues hold a very important role. A survey was
      conducted by the Laboratory of Health Informatics of the University of Athens
      concerning the awareness of future health care professionals. The results are
      discussed further down and an attempt to define profiles of training courses on
      security is made.

PMID- 10947661
TI  - Health insurance record: an additional educational tool in teaching health
      insurance.

PMID- 10947662
TI  - Computer-based-training software package dealing with nursing information systems
      for nursing practice--A NIGHTINGALE product.

PMID- 10947663
TI  - Data protection--an eternal question.
AB  - The always pertinent question of data protection in healthcare was studied
      through comparison of three surveys. The results from the surveys made 1993,
      1995, and in spring 1998 shows that a deeper understanding of data protection is
      slowly penetrating the nursing profession. When the new national data law, in
      accordance with EC-directives, will be applied from the autumn 1998, the question
      of data protection will be brought up again.

PMID- 10947664
TI  - Learning health informatics and telematics by web_DKN based knowledge
      construction and discovery.

PMID- 10947665
TI  - Information and knowledge extraction from medical texts.

PMID- 10947666
TI  - Global health informatics education.
AB  - Health informatics education has evolved since the 1960s with a strong research
      foundation primarily in medical schools across the USA and Europe. By 1989 health
      informatics education was provided in some form by at least 20 countries
      representing five continents. This continues to progress, in Europe with the help
      of a number of special projects, via the integration of informatics into pre
      registration health professional courses, undergraduate and post graduate course
      work and research degree programs. Each program is unique in terms or content and
      structure reflecting the many foundation disciplines which contribute or are
      incorporated in the health informatics discipline. Nursing informatics education
      is not as widespread. Indeed the evidence suggests a poor uptake of informatics
      by this profession. Advances in computer based educational technologies are
      making innovative modes of educational delivery possible and are facilitating a
      shift towards learner centred, flexible and life long learning. Greater
      cooperation between Universities is recommended.

PMID- 10947667
TI  - The medical informatics curriculum at the University of Heidelberg/School of
      Technology Heilbronn: new developments in its 5th revision.
AB  - We report about new developments in the 5th version of the medical informatics
      program at the University of Heidelberg/School of Technology Heilbronn, reflect
      our approaches for the revision and discuss our current curriculum in
      relationship to other curricula in health informatics and medical informatics.
      The specialised university curriculum for medical informatics at the University
      of Heidelberg/School of Technology Heilbronn is one of the oldest educational
      approaches in the field of medical informatics. During more than 25 years approx.
      1000 students graduated. The program belongs to the category of dedicated master
      programs for medical informatics and is based on the concept of medical
      informatics as a medical discipline of its own. It covers the total spectrum of
      medical informatics ranging from information systems in health care, biosignal
      and medical image processing, medical documentation, to information and knowledge
      processing in medicine. It is a 4.5 years program with a strong emphasis on the
      methodological foundations of medical informatics and on practical education in a
      number of specific laboratories. For the 5th version of the Heidelberg/Heilbronn
      curriculum on medical informatics, having started at winter semester 1997/98, we
      hope to have reflected the evolution of medical informatics as a separate
      discipline, moving one step further towards educating medical informatics, and
      not 'just' medicine and informatics.

PMID- 10947668
TI  - M.Sc. course in health informatics--an inter-university cooperation success story
      in Greece.
AB  - Health informatics is a recently established and important multi-disciplinary and
      inter-disciplinary field that not only involves informatics but also medicine,
      nursing, engineering, biology and other-related subjects. A co-ordination of this
      field at a postgraduate level becomes important now in Europe where other
      European Community programs such as the Telematics for Health Care will require
      at the Fourth Framework Programme (1994-1999) and the Fifth Framework Programme
      (2000-2006) adequate human resources of higher potential and knowledge. A
      European M.Sc. course met all the above objectives. The curriculum was developed
      according to previous experiences in similar programmes. Recently the course has
      been organised on the basis of an Inter-University nature with the participation
      of 5 Greek Universities. The paper aims at providing a description of the new
      academic programme and a brief evaluation of the implementation phase.

PMID- 10947669
TI  - Switzerland: new medical informatics curriculum.
AB  - Swiss Society for Medical Informatics (SSMI) started to build a postgraduate
      curriculum in medical informatics a year ago. The aim is to build a curriculum
      with different modules allowing the healthcare professionals to follow individual
      path in order to fulfill their objectives. The professionals who could benefit
      from the curriculum are physicians, nurses, medical assistants, computer
      specialists in the healthcare domain. Different levels of certificates or
      diplomas will be given depending on the number of modules taken and the
      professional background. Modules can be taken in different ways: universities,
      hospitals, distance learning.... The kickoff meeting for the leading group of
      this curriculum chaired by Dr Denz from Zurich was held on June 5 and 6 1998 was
      Swiss Nursing informatics group is active in this field. Working Group 5 (WG5)
      "Nursing Informatics in Europe" is supporting countries efforts in building
      nursing informatics curriculum. Promoting links between specialists in this
      domain in different countries. Selecting relevant Websites to be used.
      Disseminating information to country members of WG5.

PMID- 10947670
TI  - New nursing informatics curriculum--an outcome from the NICE project.

PMID- 10947671
TI  - Past, present and future of health and nursing informatics education at
      Noordelijke Hogeschool Leeuwarden.

PMID- 10947672
TI  - A coherent approach to health informatics education: results of the Dutch
      curriculum project.
AB  - From the beginning a coherent approach to health informatics education has been
      aimed for in our project to develop learning materials. The features are the
      thematic approach of the contents, the interrelationship of the modules and the
      didactical approach embedded in the learning materials. Following results have
      been achieved. Learning materials have been developed for the following themes:
      healthcare policy and management, delivery of professional care (specific for
      nursing and allied health), more generic themes such as electronic patient
      record, clinical decision making, classification and coding of healthcare data
      and knowledge based systems. Software made available by private companies has
      been selected for use in the learning modules. In specific cases the available
      software products did not match the criteria to support the learning materials.
      In these cases model applications have been developed that can be considered as
      forerunners for systems in practical use. Already some companies have expressed
      interest to adapt our home grown products for use in clinical practice. The
      modules are based on a model curriculum that has been developed by Aarts et al in
      1995. New developments in healthcare have prompted modification of the contents
      of a few modules. For example, a module has been redefined to cover the important
      issue of logistics in healthcare. The module on patient education has been
      adapted to take into account the resources available on the Internet. Also, new
      insights in the effectiveness of computer-based patient education have been taken
      into account. The module on informatics for disabled persons has been focussed on
      computer-based aids and is being linked to the EU-project "Impact" aimed at
      increasing knowledge about assistive technology. However, the model curriculum
      has proved to be reasonable robust as a base for our project to develop learning
      materials for health informatics.

PMID- 10947674
TI  - The situation of teaching nursing informatics in nursing education.

PMID- 10947673
TI  - Critical social theory as a model for the informatics curriculum for nursing.
AB  - It is widely acknowledged that the education and training of nurses in
      information management and technology is problematic. Drawing from recent
      research this paper presents a theoretical framework within which the nature of
      the problems faced by nurses in the use of information may be analyzed. This
      framework, based on the critical social theory of Habermas, also provides a model
      for the informatics curriculum. The advantages of problem based learning and
      multi-media web-based technologies for the delivery of learning materials within
      this area are also discussed.

PMID- 10947675
TI  - The SIP project: A national united approach to nursing informatics education in
      Denmark.
AB  - The SIP-project is a developmental project initiated by the deans of the Danish
      Nursing Schools on introducing and implementing the use and learning of Nursing
      Informatics in Danish nursing education. SIP is the acronym of SYGEPLEJE(Nursing)
      INFORMATIK (Informatics) and Paedagogik (Learning). This paper presents the
      background, structure, goals, expected and actual outcomes of the project and
      actual problems within the project. The SIP-project is a developmental project
      initiated by the deans of the Danish Nursing Schools on introducing and
      implementing the use and learning of Nursing Informatics in Danish nursing
      education. SIP is the acronym of SYGEPLEJE(Nursing) INFORMATIK (Informatics) and
      Paedagogik (Learning). This paper presents the background, structure, goals,
      expected and actual outcomes of the project and actual problems within the
      project.

PMID- 10947676
TI  - A regulated telemedicine system for day to day application in remote areas.
AB  - The NIVEMES project creates an international network of Health Service providers
      which offer Telemedicine-Teleconsultation services to Remote, Isolated places and
      to ship vessels for both routine and emergency situations. The base of the system
      is the powerful Multimedia Health Record, with the ability to manage conventional
      data, images, videos and biosignals, acquired directly from the medical device.
      National and international medical codification schemata are employed such as ICD
      X and WHO standards. Telemedicine and Computing in Health Care are rapidly
      covering a pending gap, not fulfilled by current bureaucratic and telematic
      procedures. However even from the first test fields conducted during the past
      year, it is obvious that a variety of new training needs has arisen. The users of
      such systems need to be instructed new ways of conducting their business, of
      taking advantage of the services, even a new way of perceiving health care
      provision. The user interface of the software is kept simple, thus getting
      acquainted with it requires minimum effort; however there are other issues on
      which training is required to best exploit the advantages the system offers. The
      telemedical networks spawned in each country must be co-ordinated, and the user
      needs to know where and how he/she will acquire the necessary support. Home-cared
      patients will have to operate medical devices and telemedical software, a task
      which although made easy from today's technology, it still requires some basic
      training, specially as far as elderly users are concerned. The NIVEMES system
      uncovers a set of new training needs, but it offers at the same time a vehicle
      for educating the professional health-carers. The Health Record comprises a
      multimedia, explicit account of the patient history, which can be used for
      detailed and integrated study from trainee health carers of all levels (as well
      as from officers on board, people taking care of home-confined patients and
      others), on real data or in a simulated environment. At the same time the
      telemedicine facilities may increase the effectiveness of junior doctors working
      in remote areas and enhance the confidence residents have about their local
      health centres. Systems like NIVEMES prove that new user needs arise nowadays and
      employment of modern tools requires training in modern methods and in a new way
      of thinking.

PMID- 10947677
TI  - Developing and delivering courses using a virtual classroom environment--results
      of the TALENT project.

PMID- 10947678
TI  - How an employed group redesigned itself to achieve financial viability.

PMID- 10947679
TI  - Using peer review for self-audits of medical record documentation.

PMID- 10947681
TI  - Newborn screening: A blueprint for the future executive summary: newborn
      screening task force report

PMID- 10947682
TI  - Serving the family from birth to the medical home. Newborn screening: a blueprint
      for the future - a call for a national agenda on state newborn screening programs

PMID- 10947680
TI  - Serving the family from birth to the medical home. A report from the Newborn
      Screening Task Force convened in Washington DC, May 10-11, 1999.

PMID- 10947683
TI  - The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic
      drugs: clinical and regulatory implications. Report on a Policy Conference of the
      European Society of Cardiology.

PMID- 10947684
TI  - 'For the times they are a-changing'--or are they?

PMID- 10947685
TI  - Anaesthesia for magnetic resonance imaging: a survey of current practice in the
      UK and Ireland.
AB  - The lack of information about standards for anaesthetic practice in magnetic
      resonance imaging is of concern, since increasing requests are being made for
      this service, often in units not designed for the purpose. An overview of current
      practice was sought by conducting a postal survey of magnetic resonance units in
      the UK and Ireland. Replies were received from 100 units (79%), 46 of which had
      an anaesthetic service provided. A wide diversity of practice and opinion on the
      conduct of anaesthesia in this field was evident from the replies received. The
      survey highlighted particular areas of concern about the personal safety of
      anaesthetists within such units, including exposure to magnetic fields, noise and
      unscavenged anaesthetic gases. The evidence for such concerns is reviewed.

PMID- 10947686
TI  - Correlating obstetric epidural anaesthesia performance and psychomotor aptitude.
AB  - We investigated the correlation between the scores attained on computerised
      psychometric tests, measuring psychomotor and information processing aptitudes,
      and learning obstetric epidural anaesthesia. Ten anaesthetic trainees performed
      an adaptive tracking task (ADTRACK 3) and one information management task (MAZE)
      from the MICROPAT testing system. They then embarked on a standardised obstetric
      anaesthesia training programme prior to performing obstetric on-call duties. The
      success or failure of their first 50 obstetric epidurals was recorded. There was
      a significant correlation between mean obstetric epidural failure rate for the
      second 25 consecutive epidurals and ADTRACK 3 (r = -0.579, p = 0.04) scores. The
      correlation between the means of the first 25 and 50 consecutive epidurals and
      ADTRACK 3 scores was not significant. There was no significant correlation
      between epidural failure rate and MAZE scores. The ratios of the mean epidural
      failure rate for the last 25 epidurals to the mean for the first 25 epidurals
      were not significantly correlated with ADTRACK 3 or MAZE scores. Psychomotor
      abilities appear to be poor determinants of trainees' initial proficiency at
      obstetric epidural anaesthesia or of trainees' rates of progress during early
      obstetric epidural training, but may be determinants of an individual's
      performance after the initial training phase.

PMID- 10947687
TI  - Single injection peribulbar anaesthesia. Total upper eyelid drop as an end-point
      marker.
AB  - A prospective, observer blinded study on 51 patients undergoing cataract surgery
      was conducted to assess Total Upper Eyelid Drop as a new end-point marker to
      single injection peribulbar block. At present, no such clinical marker exists to
      stop clinicians injecting more than necessary volumes of local anaesthetic and
      therefore to prevent dangerous increases in intra-ocular pressure. Using this
      technique, satisfactory ocular akinesia was achieved in 90% of eyes 10 min after
      injection. Operating conditions were satisfactory in 98% of cases. The mean
      (range) volume injected was 9.1 (4-15) ml. The mean increase in intra-ocular
      pressure immediately after injection was 6.9 mmHg, decreasing to 0.7 mmHg after 5
      min without the application of ocular compression. We found a negative
      correlation between the increase in intra-ocular pressure and the volume of
      injection (p < 0.002), which has never previously been reported. We conclude that
      Total Upper Eyelid Drop is a reliable endpoint marker for producing satisfactory
      operating conditions for cataract surgery while minimising increases in intra
      ocular pressure and its use may therefore avoid the risks associated with ocular
      compression.

PMID- 10947688
TI  - The pharmacokinetics of caudal ropivacaine 0.2% in children. A study of infants
      aged less than 1 year and toddlers aged 1-5 years undergoing inguinal hernia
      repair.
AB  - This study evaluates the pharmacokinetics of ropivacaine in children after caudal
      epidural injection. Twenty male children undergoing inguinal hernia repair were
      enrolled after ethics committee approval and informed parental consent, and were
      grouped according to age (10 'infants' aged less than 1 year and 10 'toddlers'
      aged 1-5 years). After induction of general anaesthesia, caudal epidural
      injection using ropivacaine 0.2% 1 ml.kg-1 was performed. Plasma concentrations
      of ropivacaine in the first 2 h after injection were determined by reversed-phase
      high-pressure liquid chromatography. Caudal blockade with ropivacaine 2 mg.ml-1
      resulted in mean (SD) peak plasma concentrations of 0.73 [0.27] microg.ml-1 in
      infants and 0.49 [0.21] microg.ml-1 in toddlers (p < 0.01). Maximum plasma
      concentrations occurred after a median [range] period of 60 [15-90] min and 52.5
      [30-120] min in infants and toddlers, respectively. Two infants (weighing 3.8 and
      5.0 kg) showed the highest individual maximum plasma concentrations: 1.31 and
      1.11 microg.ml-1. No clinical signs of local anaesthetic toxicity were observed.
      The results of the present investigation suggest that, from a pharmacokinetic
      point of view, caudal blockade using ropivacaine 0. 2% 1 ml.kg-1 can be regarded
      as a safe technique in children, i.e. in infants as well as in toddlers.

PMID- 10947689
TI  - The effect of intravenous epinephrine on the bispectral index and sedation.
AB  - Eight patients were given a propofol infusion until they no longer responded to
      loud verbal stimuli, a sedation score of two (modified Observer Assessment of
      Alertness and Sedation Scale). After receiving 15 microg of intravenous
      epinephrine, changes in sedation score and bispectral index (BIS) were observed.
      Mean pulse rate increased from 68 to 96 (SD 10) beat.min-1, mean blood pressure
      increased from 107/60 (SD 10/8) mmHg to 140/70 (SD 27/14) mmHg, and mean BIS
      level rose from 63 to 76 (p < 0.005). Sedation scores increased in six of the
      eight patients. Exogenous catecholamines seem to have an arousal effect on
      lightly anaesthetised patients. This could be due to changes in neurotransmitter
      levels in the brain, or due to the effects consequent on increased cardiac
      output.

PMID- 10947690
TI  - Nerve tissue protein S-100 and neurone-specific enolase concentrations in
      cerebrospinal fluid and blood during carotid endarterectomy.
AB  - Nerve tissue protein S-100 and neurone-specific enolase levels in serum were
      studied in 10 patients before, during and for 2 days after elective carotid
      endarterectomy performed under general anaesthesia and using a Javid Shunt. In
      six patients, simultaneous cerebrospinal fluid samples were also obtained. Serum
      nerve tissue protein S-100 was normal throughout the operation, but in one
      patient with severe hypertension, levels increased to 1.38 microg. l-1 at 1 h
      postoperatively. Two patients showed an increase in cerebrospinal fluid nerve
      tissue protein S-100 during clamping: these patients also had neurological
      deficits at 6 months. Serum neurone-specific enolase increased from 5.8 to 9.3
      microg.l-1 during shunting while cerebrospinal fluid neurone-specific enolase did
      not change. Uncomplicated carotid endarterectomy does not produce cerebral damage
      as measured by serum nerve tissue protein S-100; cerebrospinal fluid nerve tissue
      protein S-100 may be more sensitive for minor cerebral damage. Neurone-specific
      enolase appeared to be nonspecific. The lack of correlation between the
      neuroproteins may need to be explained before relying on these simple assays as
      diagnostic indicators of cerebral ischaemia.

PMID- 10947691
TI  - A randomised controlled trial of intravenous versus inhalational analgesia during
      outpatient oocyte recovery.
AB  - To compare the efficacy and acceptability of conventional intravenous sedation
      with patient-controlled inhalational isodesox, 57 women undergoing outpatient
      oocyte recovery were randomly allocated to receive isodesox by face mask, while
      55 women were given intravenous fentanyl and midazolam. Women's satisfaction with
      pain relief, peroperative pain, clouding of memory and the surgeons' assessment
      of operating conditions were evaluated. Thirty-eight women in the inhalation
      group (67%) and 41 (75%) women in the intravenous group were 'very satisfied'
      with their analgesia (p = 0. 41). The mean (SD) pain score in women given
      isodesox was 46.8 (34. 7), while in the intravenous group it was 34.1 (21.3) (p =
      0.02). Oxygen saturation levels < 94% were recorded in one woman using isodesox
      and in 16 (29%) women given intravenous analgesia. Despite higher pain scores, in
      comparison with the conventional analgesia, patient-controlled isodesox offers a
      safer method of pain relief with comparable satisfaction rates.

PMID- 10947692
TI  - Tracheal intubating conditions after induction with sevoflurane 8% in children. A
      comparison with two intravenous techniques.
AB  - We studied tracheal intubating conditions in 120 healthy children, aged 3-12
      years, in a blinded, randomised clinical trial. Children were randomly allocated
      to one of three groups: group PS, propofol 3 mg.kg-1 and succinylcholine 1 mg.kg
      1 (n = 40); group PA, propofol 3 mg.kg-1 and alfentanil 10 microg.kg-1 (n = 40);
      group SF, sevoflurane 8% in 60% nitrous oxide in oxygen for 3 min (n = 40).
      Tracheal intubating conditions were graded according to ease of laryngoscopy,
      position of vocal cords, coughing, jaw relaxation and movement of limbs. Overall
      intubating conditions were acceptable in 39 of 40 children in the
      propofol/succinylcholine group, 21 of 40 children in the propofol/alfentanil
      group and 35 of 40 children in the sevoflurane group. Children receiving propofol
      and succinylcholine or sevoflurane had better intubating conditions overall than
      those given propofol and alfentanil (p < 0.01). In conclusion, anaesthetic
      induction and tracheal intubation using sevoflurane 8% for 3 min is a
      satisfactory alternative to propofol with succinylcholine in children.

PMID- 10947693
TI  - Calcium and the anaesthetist.
AB  - Calcium plays a central role in a large number of physiological actions that are
      essential for life. It is important therefore that the anaesthetist understands
      calcium pathophysiology. In this review, the physiology, regulation, clinical
      features, causes and treatment of alterations in circulating calcium will be
      discussed. In addition, the effects that acid-base status, massive blood
      transfusion and cardiopulmonary bypass may have on circulating calcium will be
      highlighted. Finally, the role that calcium plays in ischaemic/reperfusion injury
      and myocardial stunning will be summarised.

PMID- 10947694
TI  - The contamination of volatile anaesthetics in an in-circle vaporizer with water
      during prolonged closed-circle anaesthesia.
AB  - The amount of water present in sevoflurane in an in-circle vaporizer after long
      procedures was measured. This demonstrated that the sevoflurane residue was
      contaminated with a small amount of water.

PMID- 10947695
TI  - A qualitative investigation into the physical stability of polypropylene and
      polyethylene in liquid isoflurane and sevoflurane.
AB  - The interaction between medical plastics and drugs is complex. Drug absorption
      into plastics may affect drug dosage and the migration of plastics' additives
      into a drug solution may affect drug composition. We investigated the stability
      of those plastics which may be used in infusion systems to inject liquid volatile
      anaesthetic drugs directly into an anaesthetic breathing system. Samples of two
      types of polypropylene from a syringe barrel and plunger and low- and high
      density polyethylene from extension tubing were exposed to isoflurane and
      sevoflurane for 1, 7 or 250 days. All samples were from the same batches. Samples
      of the plastics (n = 24) and the liquid volatile anaesthetics (n = 24) were
      subjected to Fourier transform-infrared spectroscopy to produce series of
      absorption spectra. By reference to control sample absorption spectra, this
      allows detection of anaesthetic drug absorption into the plastics or migration of
      the plastics or their additives into the liquid anaesthetics. We found no
      evidence of migration of the plastic components or their additives into the
      liquid anaesthetic drugs at any of the exposure periods. Similarly, we found no
      evidence of absorption of isoflurane or sevoflurane by any of the plastic
      components during short-term exposure of either 1 or 7 days. However, there was
      evidence of some absorption of the anaesthetic drugs by the polyethylene plastics
      after about 8 months' exposure. It would appear that low- and high-density
      polyethylene and polypropylene are suitably safe for use in infusion systems for
      the direct injection of isoflurane and sevoflurane into anaesthetic breathing
      systems.

PMID- 10947696
TI  - Supraclavicular brachial plexus block as a sole anaesthetic technique in
      children: an analysis of 200 cases.
AB  - Classical supraclavicular brachial plexus block was used as the sole anaesthetic
      technique in 200 children aged between 5 and 12 years undergoing closed reduction
      of arm fractures. The local anaesthetic used was lidocaine 1.5% with epinephrine.
      The block was graded as satisfactory if surgical manipulation could be performed
      without discomfort and unsatisfactory if general anaesthesia had to be given. In
      182 children, the procedure was carried out under the block alone, whereas the
      remaining 18 patients required general anaesthesia. The mean (SD) time required
      for performing the block was 9.1 (3.7) min and the mean (SD) time to sensory
      blockade was 8.3 (2.3) min. The mean duration of analgesia was approximately 3.5
      h. There were few complications, with no incidence of pneumothorax in any
      patient. The acceptability of the block by the children and the parents was 72
      and 85%, respectively. The classical supraclavicular brachial plexus block was
      found to be acceptable, effective and with a good success rate.

PMID- 10947697
TI  - Early release pattern of S100 protein as a marker of brain damage after warm
      cardiopulmonary bypass.
AB  - Warm blood cardioplegia may be more beneficial to the heart than cold
      cardioplegia, but the effects of warm cardiopulmonary bypass and warm blood
      cardioplegia on the brain are controversial. S100 protein is an early marker of
      brain damage and has been detected after cold cardiopulmonary bypass. We studied
      S100 concentrations in 20 patients undergoing coronary artery bypass surgery
      before and after warm cardiopulmonary bypass (34-37 degrees C) using warm blood
      cardioplegia (37 degrees C) for all patients. The peak level of S100 protein
      occurred immediately after warm cardiopulmonary bypass, then decreased
      progressively until the last measurement at 4.5 h after bypass. The peak level
      appears to be dependent upon the age of the patient, with the following
      regression equation: y = -3.2 + 0.08x, where y is S100 protein concentration in
      microg.l-1 and x is patient age in years. Further studies are needed to
      investigate the clinical significance of this early release pattern. Patient age
      should be taken into account when studying S100 protein levels after
      cardiopulmonary bypass.

PMID- 10947698
TI  - Caudal ropivacaine and ketamine for postoperative analgesia in children.
AB  - In a prospective, randomised, double-blind clinical study, we studied 32 ASA
      grade I and II boys aged 18 months to 12 years, scheduled for circumcision under
      general anaesthesia on an outpatient basis. They were randomly allocated to one
      of two groups: those in the ropivacaine group received caudal ropivacaine 0.2% 1
      ml. kg-1 for postoperative analgesia and those in the ketamine/ropivacaine group
      received caudal ropivacaine 0.2% 1 ml. kg-1 plus caudal ketamine 0.25 mg.kg-1.
      Postoperative pain was assessed using a modified 10-cm visual analogue scale and
      analgesia was administered if the pain score exceeded a value of 3. The median
      duration of analgesia was significantly longer in the ketamine/ropivacaine group
      (12 h) than in the ropivacaine group (3 h, p < 0.0001), and subjects in the
      ropivacaine group required significantly more doses of postoperative analgesia
      than those in the ketamine/ropivacaine group (p < 0.0001). There were no
      differences between the groups in the incidence of postoperative nausea,
      vomiting, sedation, emergence delirium, nightmares, hallucinations, motor block
      and urinary retention.

PMID- 10947699
TI  - Stress in trainee anaesthetists.

PMID- 10947701
TI  - Anaesthetic pre-assessment clinics to identify patients at risk.

PMID- 10947702
TI  - Pre-anaesthesia assessment clinics.

PMID- 10947703
TI  - Pre-anaesthesia assessment clinics.

PMID- 10947704
TI  - Six months acute medicine makes a better doctor, regardless of speciality!

PMID- 10947705
TI  - Airway management in the accident and emergency department.

PMID- 10947706
TI  - Intubation during manual in-line stabilisation of the head and neck.

PMID- 10947707
TI  - Training box for fibreoptics.

PMID- 10947709
TI  - Nosocomial infections related to fibreoptic intubation.

PMID- 10947710
TI  - Breathing system filters used with Entonox.

PMID- 10947713
TI  - Reducing the potential risk of cross-infection from Entonox equipment.

PMID- 10947714
TI  - Radio-opaque stripes on tracheal and tracheostomy tubes.

PMID- 10947716
TI  - Date-expired nitrous oxide cylinders found on anaesthetic machines.

PMID- 10947717
TI  - Tracheal rupture with a double-lumen tracheal tube.

PMID- 10947718
TI  - Simple apparatus for continuous nebulisation of prostacyclin.

PMID- 10947720
TI  - Use of trans-oesophageal doppler ultrasound during laparoscopic anterior
      fundoplication.

PMID- 10947722
TI  - Combined thoracic epidural and general anaesthesia with laryngeal mask airway for
      laparoscopic cholecystectomy in a patient with myasthenia gravis.

PMID- 10947723
TI  - X-ray image intensifier assisted placement of a thoracic epidural catheter.

PMID- 10947724
TI  - The sweet smell of success.

PMID- 10947725
TI  - Evoked potential monitoring in anaesthesia and analgesia.

PMID- 10947727
TI  - Hyperkalaemia, donor blood and cardiac arrest associated with ECMO priming.

PMID- 10947728
TI  - Opiate withdrawal after tramadol and patient-controlled analgesia.

PMID- 10947729
TI  - Suspected acute post-transplant neuropsychosis due to interaction of morphine and
      cyclosporin after a renal transplant.

PMID- 10947730
TI  - Are we causing latex sensitisation unknowingly?

PMID- 10947733
TI  - Succinylcholine and temporal muscle damage.

PMID- 10947732
TI  - Drugs which cause pain on intravenous injection.

PMID- 10947734
TI  - A complication with the use of metaraminol in obstetric anaesthesia.

PMID- 10947735
TI  - Use of a peripheral nerve stimulator for predicting caudal epidural analgesia.

PMID- 10947736
TI  - Kinking of epidural catheters.

PMID- 10947738
TI  - Assessing sensory blockade after regional anaesthesia.

PMID- 10947739
TI  - Spring guidewire sticks in the indwelling catheter during internal jugular vein
      catheterisation.

PMID- 10947741
TI  - Abnormal capnogragh trace.

PMID- 10947742
TI  - Beware of the cannula in the antecubital fossa.

PMID- 10947744
TI  - The anaesthetist as peri-operative physician.

PMID- 10947743
TI  - Problems with fashion.

PMID- 10947746
TI  - Prediction of the oculocardiac reflex from pre-operative linear and nonlinear
      heart rate dynamics in children.
AB  - This study was aimed to determine whether pre-operatively measured linear and
      nonlinear analysis of heart rate variability might predict the occurrence of the
      oculocardiac reflex (OCR) or other arrhythmia during strabismus surgery in
      children (n = 185, mean (SD) age = 8.09 (3.31) years). We compared time- and
      frequency-domain, and nonlinear dynamic indices of pre-operatively measured RR
      interval data between the OCR-positive group (maximum heart rate decrement = 20
      beat.min-1 during the traction of extraocular muscle, n = 54), OCR-negative group
      (< 20 beat x min(-1), n = 78) and arrhythmia-positive group (all other
      arrhythmias; n = 53). pNN50, rMSSD, high-frequency power and nonlinear prediction
      error were significantly lower in the OCR-positive and arrhythmia-positive groups
      than in the OCR-negative group. Discriminant analysis using these indices could
      correctly identify 39/54 (72.2%) OCR-positive patients. Some pre-operatively
      measured indices of linear and nonlinear heart rate variability, especially when
      used in combination, are valuable for predicting significant bradycardia during
      strabismus surgery in children.

PMID- 10947745
TI  - End-tidal oxygraphy during pre-oxygenation in patients with severe diffuse
      emphysema.
AB  - We hypothetised that the rate of pre-oxygenation could be altered by the increase
      in lung volume and airflow obstruction observed in emphysema. End-tidal oxygen
      concentration was monitored, using a paramagnetic oxygen analyser, during 10-min
      pre-oxygenation (tidal breathing of 100% oxygen) in 10 normal patients and in 10
      patients with severe diffuse emphysema documented by computerised tomography.
      Emphysema was characterised by an important increase in functional residual
      capacity of the lungs [190 (23)% of predicted values] and a decrease in
      expiratory flow. The increase in end-tidal oxygen concentration was slower in the
      emphysema group than in the control group (p = 0.0024). After 3 and 5 min of pre
      oxygenation, the end-tidal fractional oxygen concentration was significantly
      lower in the emphysema group than the control group [mean (SD); value at 3 min:
      emphysema: 0.83 (0.06) vs. control: 0.91 (0.02), p = 0.0005]. Individual values
      of end-tidal oxygen concentration measured after 3, 5 and 10 min of pre
      oxygenation were negatively correlated with functional residual capacity in the
      emphysema group, whereas no such correlation was found in the control group.
      These results suggest that pre-oxygenation should be monitored in patients with
      diffuse emphysema to ensure that adequate pre-oxygenation is achieved.

PMID- 10947747
TI  - Chemical stability of bupivacaine, lidocaine and epinephrine in pH-adjusted
      solutions.
AB  - Epinephrine and sodium bicarbonate may be added to local anaesthetic solutions in
      order to reduce the onset time and enhance the quality of epidural anaesthesia
      for Caesarean section. Such mixtures are sometimes prepared several hours in
      advance for subsequent use in emergency Caesarean section through a pre-existing
      epidural catheter. To evaluate this practice, we studied the chemical stability
      in solution over 24 h of nine epidural mixtures consisting of different
      combinations of bupivacaine, lidocaine, epinephrine and sodium bicarbonate. In
      mixtures alkalinised with sodium bicarbonate, epinephrine concentrations
      decreased significantly over 24 h (p<0.0001), whereas those in nonalkalinised
      mixtures did not change with time. Bupivacaine and lidocaine concentrations in
      all mixtures did not decrease over time regardless of alkalinisation. We do not
      recommend adding epinephrine to alkalinised epidural solutions that are to be
      stored for a prolonged period before clinical use.

PMID- 10947748
TI  - Comparison of recovery following rapacuronium, with and without neostigmine, and
      succinylcholine.
AB  - The neuromuscular blocking effects of a single dose of rapacuronium 1.5 mg x kg(
      1) with or without reversal with neostigmine have been examined in the present
      study and compared with a dose of succinylcholine 1.0 mg x kg(-1). Neuromuscular
      block was measured mechanomyographically using train-of-four stimulation.
      Complete block occurred within 1 min with both agents. Twenty-five per cent
      recovery of the first response of the train-of-four occurred in a median [range]
      time of 7.6 [5.7-11.3] min in the succinylcholine group and in 14.2 [8.8-23.6]
      and 15.1 [9.6-23.4] min in the rapacuronium groups with and without neostigmine
      reversal, respectively. Spontaneous recovery to a train-of-four ratio of 0.8 took
      33.4 [20.0-79.0] min with rapacuronium but this was reduced to about 21.2 [13.9
      33.7] min when neostigmine was administered at 25% recovery of first twitch of
      the train-of-four.

PMID- 10947749
TI  - The sedative and electroencephalographic effects of regional anaesthesia.
AB  - We studied sedation scores, the processed electroencephalogram and mean arterial
      pressure pre-operatively in patients before and after spinal (n = 15) and lumbar
      epidural (n = 15) anaesthesia. We compared them with changes occurring over time
      in a control group (n = 15), using the responsiveness component of the Observer
      Assessment of Alertness and Sedation rating scale. The electroencephalographic
      variables studied were bispectral index, 95% spectral edge frequency, median
      frequency and the power distribution between frequency bands alpha, beta, theta
      and delta. No differences were detected within groups in sedation scores before
      and after intervention, or between groups at either stage. No between-group
      differences were detected in electroencephalographic variables. In the spinal
      group, spinal anaesthesia caused an increase in bispectral index, 95% spectral
      edge frequency, median frequency and beta frequencies, and a decrease in delta
      frequencies and mean arterial pressure. The increase in beta frequencies is
      similar to that seen in patients with low plasma concentrations of midazolam and
      may represent subclinical sedation.

PMID- 10947750
TI  - Comparison of remifentanil versus regional anaesthesia in children anaesthetised
      with isoflurane/nitrous oxide. International Remifentanil Paediatric Anaesthesia
      Study group.
AB  - We compared the efficacy and safety of a remifentanil (0.25 microg x kg(-1) x
      min(-1)-based balanced anaesthetic technique with a bupivacaine-based regional
      anaesthetic technique in an open label, multicentre study in 271 ASA physical
      status 1 or 2 children aged 1-12 years. Subjects requiring major intra-abdominal,
      urological or orthopaedic surgery were randomly allocated to receive either
      intravenous remifentanil (group R; n = 185) or epidural bupivacaine (group B; n =
      86) with isoflurane/nitrous oxide for their anaesthesia. The majority of children
      in both groups (85% in group R, 78% in group B) showed no defined response to
      skin incision, and although the mean increase in systolic blood pressure (+11 mm
      Hg) was significantly greater in group R than in group B, this change did not
      represent a serious haemodynamic disturbance. More children in group R (31%)
      required interventions to treat hypotension and/or bradycardia than those in
      group B (12%), but these were easily managed by administration of fluids or
      anticholinergic drugs. Adverse events, mainly nausea and/or vomiting, occurred in
      45% of group R and 42% of group B (NS). The adverse event profile of remifentanil
      in this study was typical of a potent mu-opioid receptor agonist. Remifentanil
      was as effective as epidural or caudal block in providing analgesia and
      suppressing physiological responses to surgical stimuli in children aged between
      1 and 12 years undergoing major abdominal, urological, or orthopaedic surgery
      under isoflurane/nitrous oxide anaesthesia.

PMID- 10947751
TI  - Anaesthesia and saccadic eye movements.
AB  - During the last 10 years, there has been a vast increase in day-case surgery
      under general anaesthesia, but this has not been accompanied by research into the
      residual cognitive and motor effects during recovery from anaesthesia. Part of
      the explanation for this phenomenon is the lack of a suitable biophysical monitor
      of anaesthetic sedation. This review discusses one of the most commonly used of
      these biophysical monitors - namely saccadic eye movements. In particular, the
      efficacy of peak saccadic velocity as a monitor of sedation will be evaluated. In
      addition, the physiology and pharmacology of saccadic eye movements will be
      discussed within the context of developing other parameters of saccadic eye
      movements as novel biophysical monitors of anaesthetic sedation.

PMID- 10947752
TI  - Reserve nitrous oxide cylinders on anaesthetic machines. A survey of attitudes
      and equipment at a large DGH.
AB  - The presence of reserve nitrous oxide cylinders on anaesthetic machines is not
      necessary and potentially hazardous, wasteful and polluting. Although reserve
      nitrous oxide cylinders are routinely present on the anaesthetic machines in many
      hospitals in the UK, it is our concern that they are not checked or maintained
      properly. We examined a sample of cylinders and surveyed the practice amongst the
      anaesthetic staff in our Department with an anonymous questionnaire. This
      confirmed that: (1) the equipment is not properly maintained, 68% of cylinders
      sampled having passed a 3-year expiry date; (2) checks are of little practical
      use, are not routinely performed by anaesthetists, and only 46% of respondents
      routinely check the nitrous oxide cylinders. In conclusion, the nitrous oxide
      cylinders are not properly checked or maintained and may represent a safety
      hazard.

PMID- 10947753
TI  - Comparison of a new video-optical intubation stylet versus the conventional
      malleable stylet in simulated difficult tracheal intubation.
AB  - Handling and efficacy of a new video-optical intubation stylet were assessed in a
      simulated difficult tracheal intubation setting and compared with a conventional
      malleable stylet. Forty-five anaesthetists performed 10 tracheal intubations
      using both techniques. Laryngoscopy was performed by the observer, who created a
      grade 3 view according the classification by Cormack and Lehane. The time taken
      to place the tracheal tube and the final tracheal tube positions were documented.
      Mean (SD) intubation time for the video-optical stylet was 20.4 (7.7) s and for
      the malleable stylet 10.2 (3.3) s (p<0.01). With the video-optical stylet the
      trachea was correctly intubated in all 225 attempts; with the malleable stylet 44
      (19.6%) oesophageal and 44 (19.6%) endobronchial intubations occurred (p<0.01).
      The video-optical intubation stylet enabled us to recognise inappropriate
      tracheal tube positions and to correct them immediately. This equipment can be
      considered a reliable and effective tool for management of the difficult airway.

PMID- 10947754
TI  - Evaluation of the use of the Flexiblade.
AB  - The Flexiblade is a laryngoscope which has a 'flexible' blade. The 'front' half
      of the blade can be moved in an anterior direction during laryngoscopy, enhancing
      the view of the glottis. The degree of movement can be controlled with the lever.
      We studied 200 ASA 1 and 2 adult patients requiring tracheal intubation and the
      patients acted as their own controls. The view of the larynx was improved in 93%
      of the cases when the vocal cords were not completely visible at laryngoscopy
      with the lever in the neutral position. Ninety-seven per cent of patients with a
      Cormack and Lehane grading of 2 at normal laryngoscopy were transformed to grade
      1 when the lever of the Flexiblade was depressed and 84% of cases with a grading
      of 3 were transformed to grade 2 or 1. In four patients, there was deterioration
      in the view of the cords: three patients with grade 1 were transformed to grade 2
      and one with grade 2 to grade 3. There was no improvement in one case with grade
      2 and three with grade 3.

PMID- 10947755
TI  - Pregnancy, anaesthesia and Guillain Barre syndrome.
AB  - Two case histories of pregnant women with Guillain Barre syndrome (acute
      demyelinating polyradiculoneuritis) are reported. The first required anaesthesia
      during the second trimester for a minor surgical procedure. The second woman was
      admitted to the Intensive Care Unit in the first trimester and was ventilated for
      18 weeks. Both babies were carried to term and delivered by Caesarean section. A
      review of the management of Guillain Barre syndrome in pregnancy discusses
      anaesthetic management, intensive care and the use of plasmapheresis and gamma
      globulins. The care of pregnant women recovered from Guillain Barre syndrome is
      also discussed.

PMID- 10947756
TI  - Effects of intrathecal ketamine added to bupivacaine for spinal anaesthesia.
AB  - We prospectively studied 30 healthy female patients undergoing intracavitory
      brachytherapy applicator insertion for carcinoma of the cervix under spinal
      anaesthesia. Patients were randomly allocated to receive either intrathecal
      bupivacaine 10 mg alone or bupivacaine 7.5 mg combined with preservative-free
      ketamine 25 mg. Spinal block onset, maximum sensory level, duration of blockade,
      haemodynamic variables, postoperative analgesic requirements and adverse events
      were recorded. Onset of sensory and motor block and duration of spinal analgesia
      were comparable between groups. Duration of motor blockade was shorter (p =
      0.0416) and requirement for intravenous fluids in the peri-operative period was
      less (p = 0.0159) in the ketamine group. Significantly more patients in the
      ketamine group had adverse events, such as sedation, dizziness, nystagmus,
      'strange feelings' and postoperative nausea and vomiting. Although the addition
      of ketamine to spinal bupivacaine had local anaesthetic sparing effects, it did
      not provide extended postoperative analgesia or decrease the postoperative
      analgesic requirements. Moreover, the central adverse effects of ketamine limit
      its spinal application.

PMID- 10947757
TI  - The effect of halothane and isoflurane on plasma cytokine levels.
AB  - The aim of this study was to investigate the effect of halothane vs. isoflurane
      on cytokine production during minor elective surgery. Forty adult patients, ASA I
      II were randomly allocated to receive halothane or isoflurane. Venous samples for
      interleukin (IL)-1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha) and
      interferon-gamma (IFN-gamma) were taken before anaesthesia, before incision, at
      the end of anaesthesia and 24 h postoperatively. In both groups, IL-6 and TNF
      alpha levels remained low throughout the study period. Before incision, in both
      groups IL-1beta and IFN-gamma showed a decrease (p<0.01 for IL-1beta in
      isoflurane group and p<0.05 for the others) compared with pre-induction. By the
      end of anaesthesia and surgery, IL-1beta had increased significantly (p<0.05) and
      IFN-gamma had decreased significantly (p<0.05) in both groups compared with pre
      incisional levels. By 24 h postoperatively in both groups, IL-1beta had decreased
      significantly (p<0.05), whereas IFN-gamma had increased significantly (p<0.05)
      compared with the end of anaesthesia and surgery level. Pre-incisionally, IL-2
      increased in the halothane group (p<0.01), whereas it decreased significantly in
      the isoflurane group (p<0.001) compared with the pre-induction level. By the end
      of anaesthesia and surgery and by 24 h postoperatively, IL-2 had decreased
      significantly in the halothane group (p<0.001), whereas it increased
      significantly in the isoflurane group (p<0.001) compared with pre-incision and
      end of anaesthesia and surgery levels, respectively.

PMID- 10947758
TI  - The Do Attempt Resuscitation doctor.

PMID- 10947759
TI  - Intensive care training and non anaesthetists.

PMID- 10947760
TI  - No laughing matter--a failure of pipeline nitrous oxide supply.

PMID- 10947761
TI  - A ghost in the machine?

PMID- 10947762
TI  - The hidden leak.

PMID- 10947763
TI  - Gas leak from TEC 5 isoflurane vaporiser.

PMID- 10947764
TI  - Failed ventilation due to breakage of a tracheal tube connector.

PMID- 10947765
TI  - Problem with ECG electrode nipples.

PMID- 10947767
TI  - Risk of infection from laryngeal mask airways.

PMID- 10947769
TI  - Percutaneous tracheostomy in three morbidly obese patients using the 'Blue Rhino'
      technique.

PMID- 10947771
TI  - Another teeth protector.

PMID- 10947770
TI  - Another case of 'awkward teeth' producing a difficult intubation.

PMID- 10947772
TI  - Jaw thrust manoeuvre for repositioning the epiglottis down folded by the ILM.

PMID- 10947773
TI  - Dimensions of intubating laryngeal mask airway tracheal tube.

PMID- 10947774
TI  - Difficult tracheal intubation secondary to a tracheal diverticulum and a 90
      degree deviation in the trachea.

PMID- 10947775
TI  - Use of a pleurogram to identify the position of a misplaced subclavian catheter.

PMID- 10947776
TI  - Needle thoracocentesis fails to diagnose a large pneumothorax.

PMID- 10947777
TI  - Acute abdomen and unexplained metabolic acidosis in a chronic alcoholic.

PMID- 10947778
TI  - Refractory hypotension during carcinoid resection surgery.

PMID- 10947779
TI  - Pharyngeal abscess in a small infant presenting as upper airway obstruction and
      atlanto-axial subluxation.

PMID- 10947780
TI  - Hyperkalaemia and rapid blood transfusion.

PMID- 10947781
TI  - Olanzapine overdose.

PMID- 10947782
TI  - Dystrophia myotonica and succinylcholine.

PMID- 10947783
TI  - Human psychology applies to doctors too.

PMID- 10947784
TI  - Inadvertent isolated forearm.

PMID- 10947785
TI  - Glutathione transferase alpha and inhalation anaesthetics.

PMID- 10947787
TI  - Patient-controlled propofol infusion sedation.

PMID- 10947786
TI  - Nitrous oxide analgesia--a 'sting in the tail'.

PMID- 10947788
TI  - Patient-controlled oramorph--the future?

PMID- 10947789
TI  - Bacterial contamination during continuous epidural treatment.

PMID- 10947791
TI  - Skin damage related to regional anaesthesia.

PMID- 10947792
TI  - On the strange effects of fasting times.

PMID- 10947793
TI  - Pethidine in labour.

PMID- 10947794
TI  - Crashed and nearly burned... during a LSCS!

PMID- 10947795
TI  - Beau's lines.

PMID- 10947796
TI  - National Anaesthesia Day--who cares?

PMID- 10947797
TI  - Faulty intravenous cannulae.

PMID- 10947798
TI  - Mini-review: gephyrin, a major postsynaptic protein of GABAergic synapses.
AB  - gamma-aminobutyric acid type A (GABAA) receptors are located at the majority of
      inhibitory synapses in the mammalian brain. However, the mechanisms by which
      GABAA receptor subunits are targeted to, and clustered in, the postsynaptic
      membrane are poorly understood. Recent studies have demonstrated that gephyrin, a
      protein first identified as a component of the glycine receptor (GlyR) complex,
      is colocalized with several subtypes of GABAA receptors and is involved in the
      stabilization of postsynaptic GABAA receptor clusters. Thus, gephyrin functions
      as a clustering protein for major subtypes of inhibitory ion channel receptors.

PMID- 10947799
TI  - Mini-review: in vivo neurogenesis in the adult brain: regulation and functional
      implications.

PMID- 10947800
TI  - Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its
      natural ligand 15-deoxy-Delta12, 14-prostaglandin J2 in the regulation of
      microglial functions.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of
      a large group of nuclear receptors controlling the proliferation of peroxisomes
      that is involved in the downregulation of macrophage functions. Here, we report
      that PPAR-gamma was constitutively expressed in rat primary microglial cultures
      and that such expression was downregulated during microglial activation by
      endotoxin (LPS). The presence of the PPAR-gamma natural ligand 15-deoxy
      Delta12,14-prostaglandin J2 (15d-PGJ2) counteracted the repression of PPAR-gamma
      expression caused by LPS. In microglial cultures stimulated by LPS, interferon
      gamma (IFN-gamma) or by their combination, 15d-PGJ2 reduced the production of
      nitric oxide (NO) and the expression of inducible NO synthase (iNOS). The
      inhibitory effect was dose-dependent and did not involve an elevation of cyclic
      AMP, a second messenger known to inhibit NOS expression in microglia. In
      addition, 15d-PGJ2 down-regulated other microglial functions, such as tumour
      necrosis factor-alpha (TNF-alpha) synthesis and major histocompatibility complex
      class II (MHC class II) expression. The effects of 15d-PGJ2 occurred, at least in
      part, through the repression of two important transcription factors, the signal
      transducer and activator of transcription 1 and the nuclear factor kappaB, known
      to mediate IFN-gamma and LPS cell signalling. Our observations suggest that 15d
      PGJ2, the synthesis of which is likely to occur within the brain, could play an
      important role in preventing brain damage associated with excessive microglial
      activation.

PMID- 10947801
TI  - Localization and targeting of SCG10 to the trans-Golgi apparatus and growth cone
      vesicles.
AB  - SCG10 is a membrane-associated, microtubule-destabilizing protein of neuronal
      growth cones. Using immunoelectron microscopy, we show that in the developing
      cortex of mice, SCG10 is specifically localized to the trans face Golgi complex
      and apparently associated with vesicular structures in putative growth cones.
      Consistent with this, subcellular fractionation of rat forebrain extracts
      demonstrates that the protein is enriched in the fractions containing the Golgi
      apparatus and growth cone particles. In isolated growth cone particles, SCG10 was
      found to be particularly concentrated in the growth cone vesicle fraction. To
      evaluate the molecular determinants of the specific targeting of SCG10 to growth
      cones, we have transfected PC12 cells and primary neurons in culture with mutant
      and fusion cDNA constructs. Deletion of the amino-terminal domain or mutations
      within this domain that prevented palmitoylation at cysteines 22 and 24 abolished
      Golgi localization as well as growth cone targeting, suggesting that
      palmitoylation of the amino-terminal domain is a necessary signal for Golgi
      sorting and possibly transport of SCG10 to growth cones. Fusion proteins
      consisting of the amino-terminal domain of SCG10 and the cytosolic proteins
      stathmin or glutathione-S-transferase colocalized with a Golgi marker, alpha
      mannosidase II, and accumulated in growth cones of both axons and dendrites.
      These results reveal a novel axonal/dendritic growth cone targeting sequence that
      involves palmitoylation.

PMID- 10947802
TI  - No effect of apolipoprotein E on neuronal cell death due to excitotoxic and
      apoptotic agents in vitro and neonatal hypoxic ischaemia in vivo.
AB  - The epsilon4 allele of apolipoprotein E (apoE) is a genetic risk factor for
      Alzheimer's disease. Studies also suggest that the epsilon4 allele may be a risk
      factor for poor outcome following head trauma, brain haemorrhage and ischaemia.
      The mechanism by which the presence of an apoE epsilon4 allele and certain brain
      injuries act to predispose to Alzheimer's disease and poor outcome following
      brain injury is unknown. We questioned whether poor outcome after brain injury
      was due to direct modification by apoE protein and its gene variants of
      susceptibility to glutamate-mediated excitotoxic injury and apoptosis, mechanisms
      of cell death which occur following ischaemia and trauma. We investigated the
      effect of the presence or absence of endogenous murine apoE protein and different
      apoE isoforms in modification of the survival of murine embryonic cortical
      neurons exposed to the glutamate agonist, N-methyl-D-aspartic acid (NMDA) or
      apoptotic insult by staurosporine, and on the amount of brain injury sustained
      following a hypoxic-ischaemic insult in vivo to the brain of neonatal mice
      transgenically expressing human apoE epsilon3 or epsilon4. Our data provide
      evidence that apoE does not appear to alter neuronal viability following diverse
      types of acute neuronal insult, e.g. hypoxic-ischaemic or acute exposure to
      injurious agents in the models we have examined. This suggests that if apoE does
      modify the extent of brain damage and recovery after injury, it seems unlikely to
      be a result of direct or indirect modulation of excitotoxic or apoptotic cell
      death.

PMID- 10947803
TI  - VIP and PACAP potentiation of nicotinic ACh-evoked currents in rat
      parasympathetic neurons is mediated by G-protein activation.
AB  - The effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate
      cyclase-activating polypeptide (PACAP27 and PACAP38) on isolated parasympathetic
      neurons of rat intracardiac and submandibular ganglia were examined under voltage
      clamp using whole-cell patch-clamp recording techniques. VIP and PACAP (</= 10
      nM) selectively and reversibly increased the affinity of nicotinic acetylcholine
      receptor channels (nAChRs) for their agonists resulting in a potentiation of
      acetylcholine (ACh)-evoked whole-cell currents at low agonist concentrations. VIP
      induced potentiation was observed with either ACh or nicotine as the cholinergic
      agonist. The VIP- but not the PACAP-induced potentiation of ACh-evoked currents
      was inhibited by [Ac-Tyr1, D-Phe2]-GRF 1-29, amide (100 nM), a selective
      antagonist of VPAC1 and VPAC2 receptors; whereas the PACAP38- but not the VIP
      induced potentiation was inhibited by 100 nM PACAP6-38, a PAC1 and VPAC2 receptor
      antagonist. The signal transduction pathway mediating VIP- and PACAP-induced
      potentiation of nicotinic ACh-evoked currents involves a pertussis toxin (PTX)
      sensitive G-protein. Intracellular application of 200 microM GTPgammaS or
      GDPbetaS inhibited VIP-induced potentiation of ACh-evoked whole-cell currents.
      GTPgammaS alone potentiated ACh- and nicotine-evoked currents and the magnitude
      of these currents was not further increased by VIP or PACAP. The G-protein
      subtype modulating the neuronal nAChRs was examined by intracellular dialysis
      with antibodies directed against alphao, alphai-1,2, alphai-3 or beta G-protein
      subunits. Only the anti-Galphao and anti-Gbeta antibodies significantly inhibited
      the effect of VIP and PACAP on ACh-evoked currents. The potentiation of ACh
      evoked currents by VIP and PACAP may be mediated by a membrane-delimited signal
      transduction cascade involving the PTX-sensitive Go protein.

PMID- 10947804
TI  - Long-term consequences of early postnatal seizures on hippocampal learning and
      plasticity.
AB  - Neural activity influences the patterning of synaptic connections and functional
      organization of developing sensory and motor systems, but the long-term
      consequences of intense neural activity such as seizures in the developing
      hippocampus are not adequately understood. To evaluate the possibility that
      abnormal neural activity during early development may have long-term functional
      effects in hippocampal circuitry that plays a role in learning, memory and
      epilepsy, functional properties of hippocampal circuitry were assessed in adult
      rats that had experienced seizures induced by kainic acid on specific days during
      early postnatal development. Although previous studies have suggested that the
      immature hippocampus is relatively resistant to seizure-induced alterations
      compared with adults, independent behavioural and physiological experiments
      demonstrated that seizures evoked by kainic acid during early postnatal
      development induced a long-term loss of hippocampal plasticity manifesting as
      reduced capacity for long-term potentiation, reduced susceptibility to kindling,
      and impaired spatial learning, which was associated with enhanced paired-pulse
      inhibition in the dentate gyrus. The enhancement of inhibition and loss of
      plasticity were maximal when the seizures occurred on the first day of life, but
      were also observed when seizures were induced as late as postnatal day 14, which
      delimited a period of postnatal susceptibility in the developing rat hippocampus
      when disruption of normal neural activity by seizures produced consistent effects
      on a hippocampal-dependent behaviour and several forms of hippocampal plasticity
      implicated in learning, memory and the development of epilepsy in adulthood.

PMID- 10947805
TI  - Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage.
AB  - Interleukin-10 (IL-10) is a powerful suppressor of cellular immune responses,
      with a postulated role in brain inflammation. First, we have evaluated the role
      of this cytokine in ischaemic brain damage using IL-10 knockout (IL-10-/-) mice.
      The middle cerebral artery (MCA) was occluded in either IL-10-/- or wild-type
      animals of corresponding strain (C57Bl/6) and age. Infarct volume was assessed 24
      h later in serial brain sections. Brain infarct produced by MCA occlusion was 30%
      larger in the IL-10-/- than in wild-type mice (21. 8 +/- 1.2 vs. 16.9 +/- 1.0
      mm3, respectively; P < 0.01; Student's t-test). To further characterize these
      findings, studies were extended to in vitro models. Primary neuronal cortical
      cultures derived from IL-10-/- animals were more susceptible to both
      excitotoxicity and combined oxygen-glucose deprivation compared with cell
      cultures from wild-type mice. Moreover, when added to the culture medium,
      recombinant murine IL-10 (0.1-100 ng/mL) exerted a concentration-dependent
      prevention of neuronal damage induced by excitotoxicity in both cortical and
      cerebellar granule cell cultures taken from either strain. The accordance of in
      vivo and in vitro data allows us to suggest a potential neuroprotective role of
      IL-10 against cerebral ischaemia when administered exogenously or made available
      from endogenous sources.

PMID- 10947806
TI  - Pituitary adenylate cyclase-activating polypeptide promotes the survival of basal
      forebrain cholinergic neurons in vitro and in vivo: comparison with effects of
      nerve growth factor.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the
      vasointestinal polypeptide gene family for which neurotrophic activity has been
      postulated. PACAP mRNA is expressed in the developing and adult hippocampus,
      which is the principal target region of septal cholinergic neurons. We therefore
      studied the effects of PACAP on septal cholinergic neurons. In primary cultures
      from septum of embryonic and postnatal rats, PACAP increased the number of
      neurons immunohistochemically stained for the low-affinity nerve growth factor
      (NGF) receptor p75 and for the enzyme choline acetyltransferase (ChAT). PACAP
      also caused a corresponding increase in ChAT activity. In comparison, NGF had a
      greater effect than PACAP on the number of p75- and ChAT-positive neurons in
      these cultures. In vivo, following fimbria fornix transection, the number of
      immunohistochemically stained septal cholinergic neurons fell significantly to
      18% in rats given continuous intracerebroventricular infusion of vehicle, whereas
      in rats given NGF the number of these neurons did not differ significantly from
      unoperated controls. In PACAP-treated rats the number was 48% of unoperated
      values, which represented a significant increase compared with vehicle-treated
      rats and a significant decrease compared with NGF-treated rats or unoperated
      controls. Double-staining experiments revealed that most ChAT-positive neurons in
      rat medial septum also express PACAP receptor 1. Together the results show that
      PACAP promotes the survival of septal cholinergic neurons in vitro, and after
      injury in vivo, suggesting that PACAP acts as a neurotrophic factor influencing
      the development and maintenance of these neurons.

PMID- 10947807
TI  - Deafferentation-induced apoptosis of neurons in thalamic somatosensory nuclei of
      the newborn rat: critical period and rescue from cell death by peripherally
      applied neurotrophins.
AB  - This study shows that unilateral transection of the infraorbital nerve (ION) in
      newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic
      (VB) complex, as evidenced by terminal transferase-mediated deoxyuridine
      triphosphate-biotin nick end labelling (TUNEL) and electron miscroscopy. Double
      labelling experiments using retrograde transport of labelled microspheres
      injected into the barrel cortex, followed by TUNEL staining, show that TUNEL
      positive cells are thalamocortical neurons. The number of TUNEL-positive cells
      had begun to increase by 24 h postlesion, increased further 48 h after nerve
      section, and decreased to control levels after 120 h. Lesion-induced apoptosis in
      the VB complex is less pronounced if ION section is performed at P4, and
      disappears if the lesion is performed at P7. This time course closely matches the
      critical period of lesion-induced plasticity in the barrel cortex. Nerve growth
      factor (NGF) or brain-derived neurotrophic factor (BDNF), applied on the ION
      stump alone or in combination, are able to partially rescue thalamic neurons from
      apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION
      section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal
      transport in the ION mimics the effect of ION section. These data suggest that
      survival-promoting signals from the periphery, maybe neurotrophins, are required
      for the survival of higher-order neurons in the somatosensory system during the
      period of fine-tuning of neuronal connections. We also propose that anterograde
      transneuronal degeneration in the neonatal rat trigeminal system may represent a
      new animal model for studying the pathways of programmed cell death in vivo.

PMID- 10947808
TI  - Differential effect of oestradiol and astroglia-conditioned media on the growth
      of hypothalamic neurons from male and female rat brains.
AB  - To determine whether soluble products from different CNS regions differ in their
      ability to support oestrogen-stimulated neurite growth, hypothalamic neurons from
      sexually segregated embryos were cultured with astroglia-conditioned medium (CM)
      derived from cortex, striatum and mesencephalon, with or without 17-beta
      oestradiol 100 nM added to the medium. After 48 h in vitro, neurite outgrowth was
      quantified by morphometric analysis. Astroglia-CM from mesencephalon (a target
      for the axons of hypothalamic neurons) induced the greatest axogenic response in
      males and in this case only a neuritogenic effect could be demonstrated for
      oestradiol. On the other hand, astroglia-CM from regions that do not receive
      projections from ventromedial hypothalamus inhibited axon growth. A sexual
      difference in the response of hypothalamic neurons to astroglia-CM and oestradiol
      was found; growth of neurons from female foetuses was increased by astroglia-CM
      from mesencephalon, but no neuritogenic effect could be demonstrated for
      oestradiol in these cultures. Blot immunobinding demonstrated the presence of
      receptors for neurotrophic factors in cultures of hypothalamic neurons; Western
      blot analysis of these cultures demonstrated that oestradiol increased the
      concentration of trkB and IGF-I Rbeta, whereas trkA was not detected and the
      concentration of trkC was not modified. These results support the hypothesis that
      target regions produce some factor(s) that stimulate the growth of axons from
      projecting neurons and further indicate that in the case of males this effect is
      modulated by oestradiol, perhaps mediated through the upregulation of trkB and
      IGF-I receptors.

PMID- 10947811
TI  - Transient action of the endothelial constitutive nitric oxide synthase (ecNOS)
      mediates the development of thermal hypersensitivity following peripheral nerve
      injury.
AB  - Neuropathic pain is a disabling feature of peripheral nerve injury. Following
      injury, local inflammation and the release of mediators may contribute to ectopic
      mechanosensitivity of the nerve-trunk and pain hypersensitivity. In the present
      study we investigated whether nitric oxide (NO) action and local nitric oxide
      synthase (NOS) expression play a role in pain hypersensitivity and A fibre
      mediated ectopic hyperexcitability following a chronic constriction injury to a
      rat sciatic nerve. Using immunohistochemical methods we provide evidence for a
      unique endothelial constitutive nitric oxide synthase (ecNOS) immunoreactivity
      localized in early axonal endbulb-like structures of injured peripheral nerve
      axons. Moreover, we show that following nerve injury there is increased ecNOS
      mRNA expression within the lumbar sympathetic ganglia, and that axoplasmic
      transport in sympathetic and other axons rather than local non-neural synthesis
      accounts for its accumulation in nerve fibres. We also demonstrate here that
      local inhibition of NOS action with the broad-spectrum inhibitor NG-nitro-L
      arginine-methyl ester (L-NAME), but not more specific inhibitors of other NOS
      isoforms, has stereospecific, dose- and time-dependent analgesic effects that
      were reversed by local administration of L-arginine, the natural precursor of NO.
      In further work, using a teased fibre preparation, we show that administration of
      L-NAME, but not D-NAME, to the injury site also blocks ectopic mechanosensitivity
      of injured A-fibres. Our results indicate that an early and transient local ecNOS
      expression within early axonal endbulb-like structures, some arising from
      sympathetic axons, plays a critical role in the development of neuropathic pain.

PMID- 10947810
TI  - Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced
      seizures in metallothionein-I + II-deficient mice.
AB  - Metallothioneins (MTs) are major zinc binding proteins in the CNS that could be
      involved in the control of zinc metabolism as well as in protection against
      oxidative stress. Mice lacking MT-I and MT-II (MT-I + II deficient) because of
      targeted gene inactivation were injected with kainic acid (KA), a potent
      convulsive agent, to examine the neurobiological importance of these MT isoforms.
      At 35 mg/kg KA, MT-I + II deficient male mice showed a higher number of
      convulsions and a longer convulsion time than control mice. Three days later, KA
      injected mice showed gliosis and neuronal injury in the hippocampus. MT-I + II
      deficiency decreased both astrogliosis and microgliosis and potentiated neuronal
      injury and apoptosis as shown by terminal deoxynucleotidyl transferase-mediated
      in situ end labelling (TUNEL), detection of single stranded DNA (ssDNA) and by
      increased interleukin-1beta-converting enzyme (ICE) and caspase-3 levels.
      Histochemically reactive zinc in the hippocampus was increased by KA to a greater
      extent in MT-I + II-deficient compared with control mice. KA-induced seizures
      also caused increased oxidative stress, as suggested by the malondialdehyde (MDA)
      and protein tyrosine nitration (NITT) levels and by the expression of MT-I + II,
      nuclear factor-kappaB (NF-kappaB), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD). MT
      I + II deficiency potentiated the oxidative stress caused by KA. Both KA and MT-I
      + II deficiency significantly affected the expression of MT-III, granulocyte
      macrophage colony stimulating factor (GM-CSF) and its receptor (GM-CSFr). The
      present results indicate MT-I + II as important for neuron survival during KA
      induced seizures, and suggest that both impaired zinc regulation and compromised
      antioxidant activity contribute to the observed neuropathology of the MT-I + II
      deficient mice.

PMID- 10947809
TI  - Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in
      knock-out mice lacking the 5-HT transporter.
AB  - By taking up serotonin (5-hydroxytryptamine, 5-HT) released in the extracellular
      space, the 5-HT transporter (5-HTT) regulates central 5-HT neurotransmission.
      Possible adaptive changes in 5-HT neurotransmission in knock-out mice that do not
      express the 5-HT transporter were investigated with special focus on 5-HT1A and 5
      HT1B receptors. Specific labelling with radioligands and antibodies, and
      competitive RT-PCR, showed that 5-HT1A receptor protein and mRNA levels were
      significantly decreased in the dorsal raphe nucleus (DRN), increased in the
      hippocampus and unchanged in other forebrain areas of 5-HTT-/- vs. 5-HTT+/+ mice.
      Such regional differences also concerned 5-HT1B receptors because a decrease in
      their density was found in the substantia nigra (-30%) but not the globus
      pallidus of mutant mice. Intermediate changes were noted in 5-HTT+/- mice
      compared with 5-HTT+/+ and 5-HTT-/- animals. Quantification of [35S]GTP-gamma-S
      binding evoked by potent 5-HT1 receptor agonists confirmed such changes as a
      decrease in this parameter was noted in the DRN (-66%) and the substantia nigra (
      30%) but not other brain areas in 5-HTT-/- vs. 5-HTT+/+ mice. As expected from
      actions mediated by functional 5-HT1A and 5-HT1B autoreceptors, a decrease in
      brain 5-HT turnover rate after i.p. administration of ipsapirone (a 5-HT1A
      agonist), and an increased 5-HT outflow in the substantia nigra upon local
      application of GR 127935 (a 5-HT1B/1D antagonist) were observed in 5-HTT+/+ mice.
      Such effects were not detected in 5-HTT-/- mice, further confirming the
      occurrence of marked alterations of 5-HT1A and 5-HT1B autoreceptors in these
      animals.

PMID- 10947812
TI  - Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in
      reactive astrocytes in a rat model of mesial temporal lobe epilepsy.
AB  - Reactive gliosis is a prominent morphological feature of mesial temporal lobe
      epilepsy. Because astrocytes express glutamate receptors, we examined changes in
      metabotropic glutamate receptor (mGluR) 2/3, mGluR5 and transforming growth
      factor (TGF)-beta in glial cells of the hippocampal regions in an experimental
      rat model of spontaneous seizures. Rats that exhibited behavioural status
      epilepticus (SE) directly after 1 h of electrical angular bundle stimulation,
      displayed chronic spontaneous seizures after a latent period of 1-2 weeks as
      observed using continuous electrographic monitoring. SE resulted in hypertrophy
      of astrocytes and microglia activation throughout the hippocampus as revealed by
      immunolabelling studies. A dramatic, seizure intensity-dependent increase in
      vimentin immunoreactivity (a marker for reactive astrocytes) was revealed in CA3
      and hilar regions where prominent neuronal loss occurs. Increased vimentin
      labelling was first apparent 24 h after onset of SE and persisted up to 3 months.
      mGluR2/3 and mGluR5 protein expression increased markedly in glial cells of CA3
      and hilus by 1 week after SE, and persisted up to 3 months after SE. Double
      immunolabelling of brain sections with vimentin confirmed co-localization with
      glial fibrillary acidic protein (GFAP), mGluR2/3 and mGluR5 in reactive
      astrocytes. TGF-beta, a cytokine implicated in mGluR3-mediated neuroprotection,
      was also upregulated during the first 3 weeks after SE throughout the
      hippocampus. This study demonstrates seizure-induced upregulation of two mGluR
      subtypes in reactive astrocytes, which - together with the increased production
      of TGF-beta - may represent a novel mechanism for modulation of glial function
      and for changes in glial-neuronal communication in the course of epileptogenesis.

PMID- 10947813
TI  - Multimeric CREB-binding sites in the promoter regions of a family of G-protein
      coupled receptors related to the vertebrate galanin and nociceptin/orphanin-FQ
      receptor families.
AB  - Four related genes encoding a family of G-protein-coupled receptors (GPCRs) have
      been isolated from the mollusc Lymnaea stagnalis. The coding regions of this
      family of receptors share 97-99% sequence similarity at both the protein and
      nucleotide level, and they also share high sequence identity with vertebrate
      galanin and orphanin-FQ/nociceptin GPCR families. Analysis of the promoter
      regions reveals shared domains, some of which encode highly conserved repeating
      units. One 27-bp repeating unit, which encodes a c-AMP response element (CRE) and
      binds CREB protein, is repeated 14 times in one promoter. In situ hybridization
      showed expression of these receptors in identified neurons of several behaviourly
      important networks including those involved in feeding and ion and water
      regulation. These Lymnaea receptors are likely to represent members of a novel
      family of invertebrate neuropeptide receptors extensively regulated in response
      to intracellular signalling cascades.

PMID- 10947815
TI  - Retinal ganglion cells projecting to the nucleus of the optic tract and the
      dorsal terminal nucleus of the accessory optic system in macaque monkeys.
AB  - Using classical neuroanatomical retrograde tracing methods we investigated the
      retinal ganglion cells projecting to the nucleus of the optic tract and dorsal
      terminal nucleus of the accessory optic system (NOT-DTN) in macaque monkeys. Our
      main aim was to quantify the strength of the projection from the ipsilateral
      retina to the NOT-DTN. We therefore examined the number, distribution, and soma
      size of retinal ganglion cells involved in this projection.
      Electrophysiologically controlled small injections into the NOT-DTN revealed a
      clearly bilateral retinal projection originating mainly from the central retina
      but also involving peripheral retinal regions. Labelled cells were found nasally
      in the contralateral retina and temporally in the ipsilateral retina with some
      overlap in the fovea. The projection from the ipsilateral retina was 36-43% of
      that from the contralateral retina. On average, only 1-6% of the local population
      of ganglion cells projected to the NOT-DTN. Small soma size and large dendritic
      fields imply that in monkey rarely encountered, 'specialized' ganglion cells
      provide the direct retinal input to the accessory optic system (AOS). These
      results are discussed with respect to the symmetry of monocular horizontal
      optokinetic nystagmus (OKN) in primates.

PMID- 10947814
TI  - Evidence for glutamatergic tectotectal neurons in the cat superior colliculus: a
      comparison with GABAergic tectotectal neurons.
AB  - The tectotectal commissural pathway is commonly regarded as responsible for the
      reciprocal inhibition that takes place between the two superior colliculi (SC).
      Although this hypothesis has received strong support from electrophysiological
      studies, more recent investigations have suggested that some collicular cells,
      e.g. fixation neurons, may establish excitatory connections with cells in the
      contralateral SC through the collicular commissure. The goal of the present study
      was to seek immunohistochemical evidence for glutamatergic tectotectal cells in
      the cat SC by using a double-labelling technique. Tectotectal cells were
      retrogradely labelled with wheat germ agglutinin (WGA) -horseradish peroxidase
      (HRP) coupled to colloidal gold injected in the contralateral SC, and neurons
      containing glutamate or gamma-aminobutyric acid (GABA) were then identified with
      immunohistochemical techniques. The present study provides evidence that, in the
      cat SC, equal numbers of tectotectal cells are immunopositive to glutamate and
      GABA, suggesting that the tectotectal pathway may consist of two distinct
      functional components. The finding that an equal number of tectotectal cells are
      GABAergic and glutamatergic is somewhat surprising as electrophysiological
      studies have invariantly indicated that the inhibitory component of the
      tectotectal projection predominates. Another striking feature of the GABAergic
      and glutamatergic tectotectal cell populations is their identical topographic
      distribution in the SC. These results suggest that not only cells in the rostral
      fixation zone establish excitatory connections with the contralateral SC.
      Tectotectal projections could be potentially important to shape the spatial
      pattern of saccade-related activity that may occur simultaneously in the two SC
      during vertical and oblique orienting movements.

PMID- 10947816
TI  - A blocker-resistant, fast-decaying, intermediate-threshold calcium current in
      palaeocortical pyramidal neurons.
AB  - The whole-cell patch-clamp technique was used to record Ca2+ currents in acutely
      dissociated neurons from layer II of guinea-pig piriform cortex (PC). Ba2+ (5 mM)
      was used as charge carrier. In a subpopulation of layer II cells ( approximately
      22%) total Ba2+ currents (IBas) displayed a high degree (> 70%) of inactivation
      after 300 ms of steady depolarization. The application of L-, N- and P/Q-type
      Ca2+-channel blockers to these high-decay IBas left their fast inactivating
      component largely unaffected. The inactivation phase of the blocker-resistant,
      fast-decaying IBa thus isolated had a bi-exponential time course, with a fast
      time constant of approximately 20 ms and a slower time constant of approximately
      100 ms at voltage levels positive to -10 mV. The voltage dependence of activation
      of the blocker-resistant, fast-decaying IBa was shifted by approximately 7-9 mV
      in the negative direction in comparison with those of other pharmacologically
      and/or kinetically different high-voltage-activated Ca2+ currents. We named this
      blocker-resistant, fast-decaying, intermediate-threshold current IRfi. The
      amplitude of IRfi decreased only slightly (by approximately 9%) when
      extracellular Ca2+ was substituted for Ba2+, in contrast with that of slowly
      decaying, high-voltage-activated currents, which was reduced by approximately 41%
      on average. Moreover, IRfi was substantially inhibited by low concentrations of
      Ni2+ (50 microM). We conclude that IRfi, because of its fast inactivation
      kinetics, intermediate threshold of activation and resistance to organic
      blockers, represents a definite, identifiable Ca2+ current different from
      classical high-voltage-activated currents and clearly distinguishable from
      classical IT. The striking similarity found between IRfi and Ca2+ currents
      resulting from heterologous expression of alpha1E-type channel subunits is
      discussed.

PMID- 10947817
TI  - Enhancement of persistent Na+ current by sea anemone toxin (ATX II) exerts dual
      action on hippocampal excitability.
AB  - We used anemone toxin II (ATX II) to study how a selective enhancement of
      persistent Na+ current (INaP) would affect the excitability of CA1 pyramidal
      neurons in the hippocampal slice. In whole-cell recordings from CA1 cell somata,
      local application of ATX II (10 microM) into the stratum pyramidale invariably
      depolarized the neurons and produced sustained burst discharges with depolarizing
      plateau potentials of variable amplitude and length. However, the strong
      excitatory action of ATX II, observed on the single cell level, was not mirrored
      in field potential recordings from the same hippocampal subfield. The amplitude
      of the electrically evoked population spike declined, reflecting the decreased
      availability of fast Na+ channels, and the intracellulary recorded burst
      discharges were not detected by the field electrode. The lacking synchronization
      of cellular bursting activity was seen during both local and bath application of
      ATX II, suggesting that the toxin, in addition to promoting burst discharges of
      individual neurons, simultaneously dampens network excitability. In fact, ATX II
      reduced afferent fibre volleys (reflecting axonal excitability) and field
      excitatory postsynaptic potentials (EPSPs) in a similar fashion. As the
      expression of different Na+ channel subtypes appears to be compartmentalized
      within hippocampal neurons, we propose that point mutations leading to
      pathologically enhanced INaP might exert quite opposite effects, depending on the
      type and location of the Na+ channel affected. Whereas alterations of
      somatodendritic Na+ channels would give rise to bursting activity, alterations of
      axonal Na+ channels would primarily decrease network excitability.

PMID- 10947818
TI  - Dedifferentiation of intrinsic response properties of motoneurons in organotypic
      cultures of the spinal cord of the adult turtle.
AB  - Explant cultures from the spinal cord of adult turtles were established and used
      to study the sensitivity of the intrinsic response properties of motoneurons to
      the changes in connectivity and milieu imposed by isolation in culture.
      Transverse sections 700 microm thick were explanted on cover slips and maintained
      in roller-tube cultures in medium containing serum and the growth factors brain
      derived neurotrophin factor (BDNF), neurotrophin-3 (NT3), glial cell line-derived
      neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF). The gross
      morphology of acute sections was maintained after 4 weeks in culture. Cell bodies
      of motoneurons remained stainable in fixed cultures with an antibody against
      choline acetyltransferase (ChAT) throughout the culture period. During culture,
      motoneurons maintained stable resting membrane potentials and were contacted by
      functional synapses. The ability to generate action potentials was also preserved
      as was delayed inward rectification and generation of calcium spikes in the
      presence of tetra-ethyl ammonium (TEA). In response to depolarization, however,
      motoneurons presented strong outward rectification, and only 41% of the cells
      recorded from maintained the ability to fire repetitively. By the second week in
      culture, a fraction of motoneurons displayed fast and slow transient outward
      rectification and low-threshold calcium spikes, features not seen in turtle
      motoneurons in acute slices. On the other hand, properties mediated by L-type
      Ca2+ channels disappeared during the first few days in culture. Our observations
      show that the phenotypical intrinsic response properties of mature spinal
      motoneurons are modified in explant cultures. The properties acquired resemble
      the properties in juvenile motoneurons in several species of terrestrial
      vertebrates.

PMID- 10947819
TI  - The morphological development of neurons derived from EGF- and FGF-2-driven human
      CNS precursors depends on their site of integration in the neonatal rat brain.
AB  - Neural precursor cells derived from the developing human brain were expanded in
      vitro under the influence of fibroblast growth factor-2 (FGF-2) and epidermal
      growth hormone (EGF), and were then transplanted into different regions of the
      neonatal rat brain. Four weeks later neurons were seen to have developed from
      human embryonic precursors, using a human-specific antibody to tau (htau). There
      were morphological differences between implanted neurons developing in the
      hippocampus, striatum and neocortex, which were confirmed by cell volume
      measurements, although no specific neurochemical phenotypes were identified. Htau
      positive fibres were seen to project extensively along fibre pathways appropriate
      for the site of neuronal integration. This study demonstrates that, following
      cell division in vitro, neurons differentiating from human precursor cell
      populations retain the ability to respond appropriately to regional determinants
      present in the neonatal rat brain. This is important for the application of such
      cells in CNS repair strategies, in particular neural transplantation.

PMID- 10947820
TI  - Porcine neural progenitors require commitment to the oligodendrocyte lineage
      prior to transplantation in order to achieve significant remyelination of
      demyelinated lesions in the adult CNS.
AB  - Glial cell transplantation is a potential therapy for human demyelinating
      disease, though obtaining large numbers of oligodendrocyte precursors from
      nonrodent species is currently problematic. Culturing of multipotent neural
      progenitors may provide a solution to this problem, because these cells can be
      expanded in vitro whilst retaining the ability to differentiate into both neurons
      and glial cells. In order to investigate the myelinating capability of
      multipotent neural progenitors, we isolated cells from the porcine subventricular
      zone, a region rich in neural progenitors, and transplanted them into areas of
      persistent demyelination in the spinal cord of immunosuppressed rats, created by
      the injection of ethidium bromide and subsequent exposure to 40 Gy X-irradiation.
      Porcine SVZ cells were transplanted either within 12 h of isolation or after 7
      days in B104-conditioned medium. Freshly isolated cells did not mature into
      myelinating oligodendrocytes following transplantation and instead remained as
      clusters of undifferentiated progenitors. However, cells exposed to B104
      conditioned medium prior to transplantation were able to effect complete
      remyelination of the demyelinated axons. This suggests that neural progenitors
      must be manipulated in vitro for commitment to the oligodendrocyte lineage prior
      to transplantation if significant remyelination is to be achieved.

PMID- 10947821
TI  - Functional organization of auditory cortex in the Mongolian gerbil (Meriones
      unguiculatus). III. Anatomical subdivisions and corticocortical connections.
AB  - The auditory cortex of the Mongolian gerbil comprises several physiologically
      identified fields, including the primary (AI), anterior (AAF), dorsal (D),
      ventral (V), dorsoposterior (DP) and ventroposterior (VP) fields, as established
      previously with electrophysiological [Thomas et al. (1993) Eur. J. Neurosci., 5,
      882] and functional metabolic techniques [Scheich et al. (1993) Eur. J.
      Neurosci., 5, 898]. Here we describe the cyto-, myelo- and chemoarchitecture and
      the corticocortical connections of the auditory cortex in this species. A central
      area of temporal cortex corresponding to AI and the rostrally adjacent AAF is
      distinguished from surrounding cortical areas by its koniocortical
      cytoarchitecture, by a higher density of myelinated fibres, predominantly in
      granular and infragranular layers, and by characteristic patterns of
      immunoreactivity for the calcium-binding protein parvalbumin (most intense
      staining in layers III/IV and VIa) and for the cytoskeletal neurofilament protein
      (antibody SMI-32; most intense staining in layers III, V and VI). Concerning the
      cortical connections, injections of the predominantly anterograde tracer biocytin
      into the four tonotopically organized fields AI, AAF, DP and VP yielded the
      following labelling patterns. (i) Labelled axons and terminals were seen within
      each injected field itself. (ii) Following injections into AI, labelled axons and
      terminals were also seen in the ipsilateral AAF, DP, VP, D and V, and in a
      hitherto undescribed possible auditory field, termed the ventromedial field (VM).
      Similarly, following injections into AAF, DP and VP, labelling was also seen in
      each of the noninjected fields, except in VM. (iii) Each field projects to its
      homotopic counterpart in the contralateral hemisphere. In addition, field AI
      projects to contralateral AAF, DP and VP, field DP to contralateral AI and VP,
      and field VP to contralateral AI and DP. (iv) Some retrogradely filled pyramidal
      neurons within the areas of terminal labelling indicate reciprocal connections
      between most fields, both ipsilateral and contralateral. (v) The labelled fibres
      within the injected and the target fields, both ipsilateral and contralateral,
      were arranged in continuous dorsoventral bands parallel to isofrequency contours.
      The more caudal the injection site in AI the more rostral was the label in AAF.
      This suggests divergent but frequency-specific connections within and, at least
      for AI and AAF, also across fields, both ipsilateral and contralateral. (vi)
      Projections to associative cortices (perirhinal, entorhinal, cingulate) and to
      other sensory cortices (olfactory, somatosensory, visual) from AAF, DP and VP
      appeared stronger than those from AI. These data support the differentiation of
      auditory cortical fields in the gerbil into at least 'core' (AI and AAF) and
      'noncore' fields. They further reveal a complex pattern of interconnections
      within and between auditory cortical fields and other cortical areas, such that
      each field of auditory cortex has its unique set of connections.

PMID- 10947822
TI  - Functional organization of auditory cortex in the Mongolian gerbil (Meriones
      unguiculatus). IV. Connections with anatomically characterized subcortical
      structures.
AB  - The subcortical connections of the four tonotopically organized fields of the
      auditory cortex of the Mongolian gerbil, namely the primary (AI), the anterior
      (AAF), the dorsoposterior (DP) and the ventroposterior field (VP), were studied
      predominantly by anterograde transport of biocytin injected into these fields. In
      order to allow the localization of connections with respect to subdivisions of
      subcortical auditory structures, their cyto-, fibre- and chemoarchitecture was
      characterized using staining methods for cell bodies, myelin and the calcium
      binding protein parvalbumin. Each injected auditory cortical field has
      substantial and reciprocal connections with each of the three subdivision of the
      medial geniculate body (MGB), namely the ventral (MGv), dorsal (MGd) and medial
      division (MGm). However, the relative strengths of these connections vary: AI is
      predominantly connected with MGv, AAF with MGm and MGv, and DP and VP with MGd
      and MGv. The connections of at least AI and MGv are topographic: injections into
      caudal low-frequency AI label laterorostral portions of MGv, whereas injections
      into rostral high-frequency AI label mediocaudal portions of MGv. All
      investigated auditory fields send axons to the suprageniculate, posterior
      limitans, laterodorsal and lateral posterior thalamic nuclei, with strongest
      projections from DP and VP, as well as to the reticular and subgeniculate
      thalamic nuclei. AI, AAF, DP and VP project to all three subdivisions of the
      inferior colliculus, namely the dorsal cortex, external cortex and central
      nucleus ipsilaterally and to the dorsal and external cortex contralaterally. They
      also project to the deep and intermediate layers of the ipsilateral superior
      colliculus, with strongest projections from DP and VP to the lateral and
      basolateral amygdaloid nuclei, the caudate putamen, globus pallidus and the
      pontine nuclei. In addition, AAF and particularly DP and VP project to
      paralemniscal regions around the dorsal nucleus of the lateral lemniscus (DNLL),
      to the DNLL itself and to the rostroventral aspect of the superior olivary
      complex. Moreover, DP and VP send axons to the dorsal lateral geniculate nucleus.
      The differences with respect to the existence and/or relative strengths of
      subcortical connections of the examined auditory cortical fields suggest a
      somewhat different function of each of these fields in auditory processing.

PMID- 10947824
TI  - Stage of specification of the spinal cord and tectal projections from cortical
      grafts.
AB  - In order to determine the embryonic age at which the hodological phenotype
      developed by neocortical cells is specified, we have examined the spinal or
      tectal projections developed by embryonic (E) grafts of presumptive frontal or
      occipital neocortex placed into the frontal or occipital neocortex of newborn
      host rats. Grafts of E13, E14 and E16 cells of the frontal cortex transplanted
      into the occipital cortex of newborns are capable of developing and maintaining
      in adulthood a spinal cord axon. Grafts of E12 cells do not project to the spinal
      cord but send fibres to the superficial layers of the tectum. In addition,
      following transplantation into the frontal cortex, early embryonic (E12) cells
      from the presumptive occipital cortex are capable of differentiating into neurons
      with spinal cord projection but are practically incapable of developing a tectal
      projection. When grafted at E14 into the frontal cortex, occipital cells lose the
      capacity to project to the spinal cord but become able to send fibres to the
      tectum. Taken together, these findings indicate that young (E12) embryonic
      frontal and occipital cortical cells are competent to subsequently differentiate
      into neurons projecting to the spinal cord or tectum according to instructive
      signals available in the cortical territory where they complete their
      development. By E13/E14, some cortical cells are specified and their capacity to
      contact targets that are not appropriate to their embryonic origin is much
      reduced. These findings are consistent with the notion that cortical
      specification involves progressive restriction in cell multipotentiality and fate
      specification toward region-specific phenotypes.

PMID- 10947823
TI  - Calcium mobilization elicited by two types of nicotinic acetylcholine receptors
      in mouse substantia nigra pars compacta.
AB  - Nicotinic acetylcholine receptors (nAChRs) are expressed in the midbrain
      ascending dopaminergic system, a target of many addictive drugs. Here we assessed
      the intracellular Ca2+ level by imaging fura-2-loaded cells in substantia nigra
      pars compacta in mouse brain slices, and we examined the influence on this level
      of prolonged exposures to nicotine using mice lacking the nAChR beta2-subunit. In
      control cells, superfusion with nicotine (10-100 microM) caused a long-lasting
      rise of intracellular Ca2+ level which depended on extracellular Ca2+. This
      nicotinic response was almost completely absent in beta2-/- mutant mice, leaving
      a small residual response to a high concentration (100 microM) of nicotine which
      was inhibited by the alpha7-subunit-selective antagonist, methyllycaconitine.
      Conversely, the alpha7-subunit-selective agonist choline (10 mM) caused a
      methyllycaconitine-sensitive increase in intracellular Ca2+ level both in wild
      type and beta2-/- mutant mice. Nicotine-elicited Ca2+ mobilization was reduced by
      the Na+ channel blocker tetrodotoxin (TTX) and by T-type Ca2+ channel blocking
      agents, whereas the choline-elicited Ca2+ increase was insensitive to TTX.
      Neither nicotine nor choline produced Ca2+ increase following inhibition of the
      release of Ca2+ from intracellular stores by dantrolene. These results
      demonstrate that in nigral dopaminergic neurons, nicotine can elicit Ca2+
      mobilization via activation of two distinct nAChR subtypes: that of beta2-subunit
      containing nAChR followed by activation of Na+ channel and T-type Ca2+ channels,
      and/or activation of alpha7-subunit-containing nAChR. The Ca2+ influx due to
      nAChR activation is subsequently amplified by the recruitment of intracellular
      Ca2+ stores. This Ca2+ mobilization may possibly contribute to the long-term
      effects of nicotine on the dopaminergic system.

PMID- 10947826
TI  - Intracerebral infusion of H-dopamine and H-mannitol in the striatum of halothane
      anaesthetized male rats. A dual-probe microdialysis study of long-distance
      diffusion.
AB  - This report characterizes an in vivo intracerebral long-distance diffusion model
      using dual-probe microdialysis. Two probes 1 mm apart were implanted into the
      striatum of control and 6-hydroxydopamine (6-OHDA)-lesioned halothane
      anaesthetized male rats. Either tritiated dopamine (500 nM 3H-DA) or mannitol
      (1.5 microM 3H-mannitol) was infused continuously for 5 h, while samples were
      collected from the other probe. Samples (10 microl) were counted by liquid
      scintillation. For the DA-infused rats, another 10 microL was separated with high
      pressure liquid chromatography (HPLC)-electrochemical detection into individual
      fractions containing 3,4-dihydroxy phenylacetic acid (DOPAC) and homovanillinic
      acid (HVA), and counted for beta-decay. The total transfer of 3H-labelled
      compounds described the overall effect of cellular uptake, metabolism and
      clearance into the microcirculation, and was compared with that of an
      extracellular marker, 3H-mannitol. The migration reached steady-state levels,
      generating an equilibrium between delivery and removal from the extracellular
      space. The half-time of the steady-state values, t50%, was in all cases lower in
      6-OHDA-treated rats compared with control. In addition, the t50% values of 3H
      mannitol were lower than those following the 3H-dopamine infusion in both control
      or 6-OHDA-lesioned rats. However, it was not possible to detect any unmetabolized
      3H-dopamine at the 1 mm distance. In conclusion, the dual-probe microdialysis
      approach proved to be a valid method to study in vivo diffusion and migration in
      the brain, and the intracerebral spread of compounds highly depends on the nature
      of the compound infused.

PMID- 10947825
TI  - SDF-1alpha-mediated modulation of synaptic transmission in rat cerebellum.
AB  - The functional expression of the seven-transmembrane domain G protein-coupled
      chemokine receptor CXCR-4/fusin in rat nerve cell was demonstrated by staining
      with a polyclonal anti-CXCR-4 Ab, and by evaluating the calcium responses to the
      physiological agonist stromal-derived cell factor-1alpha (SDF-1alpha) in both
      cerebellar granule cells in culture and Purkinje neurons (PNs) in cerebellar
      slices. Cerebellar glial, granule and Purkinje cells showed a pronounced staining
      for CXCR-4. Furthermore, cultured granule cells exhibited Ca2+ transients
      elicited by the application of SDF-1alpha, both in cell bodies and in neuronal
      processes. Whole-cell patch-clamped PNs in cerebellar slices responded to SDF
      1alpha application by a slow inward current followed by an increase of both
      intracellular Ca2+ level and spontaneous synaptic activity. In particular, the
      SDF-1alpha-induced slow inward current was considerably reduced by ionotropic
      glutamate receptor blockers, but developed fully in a medium in which synaptic
      transmission was inhibited, indicating that this current might be, at least in
      part, mediated by extrasynaptic glutamate, possibly released from the surrounding
      glial and/or nerve cells. Taken together, these findings indicate a functional
      involvement of CXCR-4 in the modulation of synaptic transmission, adding another
      member to the repertoire of the chemokine receptors exerting a neuromodulatory
      role in the cerebellum.

PMID- 10947827
TI  - Spatial and cortical influences exerted on cuneothalamic and thalamocortical
      neurons of the cat.
AB  - This work aimed to study the responses of cuneothalamic and thalamocortical cells
      to electrical stimulation of the body surface in alpha-chloralose-anaesthetized
      cats. It was found that both classes of cells had a central excitatory receptive
      field, an edge overlapping the field centre whose stimulation elicited inhibitory
      excitatory (cuneothalamic cells) and excitatory-inhibitory (thalamocortical
      cells) sequences, and a surrounding or peripheral area usually being inhibitory.
      Manipulating the descending corticofugal activity by removing the fronto-parietal
      cortex, electrical stimulation, or by placing picrotoxin or muscimol over the
      sensorimotor cortex demonstrated that the cortical feedback potentiated effects
      driven from the field centre and the surround. In particular this potentiated
      centre-driven excitation and surround-driven inhibition, but some of the data
      points to more complex patterns. The inhibition elicited in cuneothalamic cells
      from the edge and the surround of the field was faster than the excitation
      induced from the field centre. Effects at the edge of the field centre included
      late excitatory responses relayed via the cerebral cortex. There were also direct
      corticofugal excitatory inputs to the field centre. Excitatory surrounds were
      occasionally observed, the assumption being that in most cases these were
      suppressed by the enhanced inhibition driven from the cortex. The data indicate
      that the cortico-subcortical feedback contributes not only to enhance the
      surround antagonism of a centre response but also to increase the time resolution
      of thalamic and cuneate relay somesthetic neurons.

PMID- 10947828
TI  - Synaptic plasticity in the basolateral amygdala in transgenic mice expressing
      dominant-negative cAMP response element-binding protein (CREB) in forebrain.
AB  - Electrophysiological and behavioural experiments were performed in transgenic
      mice expressing a dominant-negative form of cAMP response element-binding protein
      (CREBA133) in the limbic system. In control littermate in vitro slice
      preparation, tetanizing the lateral amygdala-basolateral amygdala (BLA) pathway
      with a single train (100 Hz for 1 s) produced short-term potentiation (STP) in
      the BLA. Five trains (10-s interstimulus interval) induced long-term potentiation
      (LTP), which was completely blocked by the N-methyl-D-aspartate (NMDA) receptor
      antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM). When
      GABAergic (gamma-aminobutyric acid) inhibition was blocked by picrotoxin (10
      microM), LTP became more pronounced. Low-frequency stimulation (1 Hz for 15 min)
      induced either long-term depression (LTD) or depotentiation. LTD remained
      unaffected by AP5 (50 microM) or by the L- and T-type Ca2+-channel blockers
      nifedipine (20 microM) and Ni2+ (50 microM), but was prevented by picrotoxin (10
      microM), indicating a GABAergic link in the expression of LTD in the BLA. When
      conditioned fear was tested, a mild impairment was seen in one of three
      transgenic lines only. Although high levels of mRNA encoding CREBA133 lead to
      downregulation of endogenous CREB, expression of LTP and depotentiation were
      unaltered in BLA of these transgenic animals. These results could suggest that
      residual CREB activity was still present or that CREB per se is dispensable.
      Alternatively, other CREB-like proteins were able to compensate for impaired CREB
      function.

PMID- 10947829
TI  - The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes after
      entorhinal cortex lesions in adult rats.
AB  - The chondroitin sulphate proteoglycan brevican is one of the most abundant
      extracellular matrix molecules in the adult rat brain. It is primarily
      synthesized by astrocytes and is believed to influence astroglial motility during
      development and under certain pathological conditions. In order to study a
      potential role of brevican in the glial reaction after brain injury, its
      expression was analysed following entorhinal cortex lesion in rats (12 h, 1, 2,
      4, 10, 14 and 28 days and 6 months post lesion). In situ hybridization and
      immunohistochemistry were employed to study brevican mRNA and protein,
      respectively, in the denervated outer molecular layer of the fascia dentata and
      at the lesion site. In both regions brevican mRNA was upregulated between 1 and 4
      days post lesion. The combination of in situ hybridization with
      immunohistochemistry for glial fibrillary acidic protein demonstrated that many
      brevican mRNA-expressing cells are astrocytes. In the denervated zone of the
      fascia dentata, immunostaining for brevican was increased by 4 days, reached a
      maximum by 4 weeks and remained detectable up to 6 months post lesion. Electron
      microscopic immunocytochemistry showed that brevican is a component of the
      extracellular matrix compartment. At the lesion site a similar time course of
      brevican upregulation was observed. These data demonstrate that brevican is
      upregulated in areas of brain damage as well as in areas denervated by a lesion.
      They suggest a role of brevican in reactive gliosis and are compatible with the
      hypothesis that brevican is involved in the synaptic reorganization of denervated
      brain areas.

PMID- 10947830
TI  - Glucocorticoid receptor impairment enhances impulsive responding in transgenic
      mice performing on a simultaneous visual discrimination task.
AB  - Transgenic mice with impaired glucocorticoid receptor (GR) function were tested
      for their ability to learn and perform a series of simultaneous visual
      discriminations which allowed a dissociation between accuracy of discrimination
      from those of motivation and behavioural disinhibition. Animals were first
      trained on an operant five-choice simultaneous discrimination autoshaping
      procedure, followed by a continuous reinforcement schedule on that task.
      Subsequently, the number of choices was limited to two and data were analysed
      according to the mathematical methods of signal detection theory (SDT). The
      effects of GR-antisense expression on accuracy when different rates of responding
      were required were studied under different fixed ratio response requirements (FR1
      FR10). Autoshaping was retarded in transgenic animals and accuracy was impaired
      in both the five-choice and the two-choice discrimination tasks, although
      transgenic mice showed clear evidence for learning. Under conditions of low
      response requirements, transgenic mice showed increased response and cognitive
      biases, but reduced perceptual bias, and a behavioural disinhibition,
      characterized by a reduction in errors of omission, decreased response latencies
      and increased number of responses during the inter-trial interval. Increasing the
      response requirement improved performance in transgenic animals as reflected by
      enhanced accuracy. Moreover, transgenics were less susceptible to the deleterious
      effects of higher response requirements, as indicated by relatively unaffected
      bias measures in this group, while bias increased in controls. These results
      indicate that altered performance in GR-antisense transgenic animals cannot
      simply be interpreted as a mnemonic deficit, but that altered motivation and
      enhanced impulsive responding may account for some of these impairments.

PMID- 10947831
TI  - The accuracy of sound duration representation in the human brain determines the
      accuracy of behavioural perception.
AB  - In recent years, the links between neural activity and perception have been an
      area of interest in cognitive neuroscience. Combined psychophysiological and
      psychophysical experiments provide a new powerful tool for establishing the
      relationship between neural activity and perceptual performance. In animals,
      intracellular recordings combined with psychophysical detection indices have
      revealed that a particular neuron or set of neurons can play a critical role in
      the generation of a perceptual event, showing detection functions (referred to as
      neurometric functions) which are remarkably similar to psychophysical detection
      functions, or psychometric functions (Parker & Newsome, (1998) Annu. Rev.
      Neurosci. , 21, 227-277). As noninvasive techniques for recording neural activity
      are now available, studies combining neuroelectric and psychophysical measures in
      humans are sparse. In the present study, the accuracy of the human brain in
      detecting differences in sound duration and the subject's ability to perceive the
      same differences were tested by means of mismatch negativity (MMN) and the
      distance between the distributions of false alarms and hits (sensitivity index
      d'), respectively. It was found that the accuracy of the human auditory system to
      represent sound duration information is related to the duration context in which
      the sounds are heard, and that these contextual representations determine the
      accuracy of perception at the behavioural level.

PMID- 10947832
TI  - Deficits of spatial and non-spatial memory and of auditory fear conditioning
      following anterior thalamic lesions in mice: comparison with chronic alcohol
      consumption.
AB  - This study was aimed at determining (i) whether or not bilateral subtotal lesions
      of the anterior thalamic nuclei (ATH) in rodents produced memory deficits for
      spatial and/or non-spatial information and of auditory fear conditioning, and
      (ii) if these eventual deficits resemble those produced by chronic alcohol
      consumption (CAC). Working memory was assessed using both spatial (spontaneous
      alternation) and non-spatial (temporal alternation) delayed response tasks.
      Results showed that ATH lesions induced delay-dependent memory impairments in
      both spatial and non-spatial alternation tasks, as well as a decreased level of
      auditory and background contextual fear conditioning compared with respective
      controls. CAC did not induce accelerated rate of forgetting in the spatial and
      non-spatial tasks, but increased the vulnerability to interference in the spatial
      task. CAC impaired only background contextual fear conditioning. We conclude that
      ATH nuclei are involved in the maintenance of information over time, regardless
      of the nature (spatial vs. non-spatial) of the information, and play a role in
      associative processes for both unimodal (the tone) and polymodal (contextual)
      information. In contrast, ATH dysfunction does not account for the memory
      disorders induced by the CAC treatment. Our results contribute to showing that
      the functional overlap between the structures comprising the hippocampo-mamillo
      thalamic pathway is only partial.

PMID- 10947833
TI  - Species-specific modulation of pattern-generating circuits.
AB  - Phylogenetic comparison can reveal general principles governing the organization
      and neuromodulation of neural networks. Suitable models for such an approach are
      the pyloric and gastric motor networks of the crustacean stomatogastric ganglion
      (STG). These networks, which have been well studied in several species, are
      extensively modulated by projection neurons originating in higher-order ganglia.
      Several of these have been identified in different decapod species, including the
      paired modulatory proctolin neuron (MPN) in the crab Cancer borealis [Nusbaum &
      Marder (1989) J. Neurosci., 9,1501-1599; Nusbaum & Marder (1989), J. Neurosci.,
      9, 1600-1607] and the apparently equivalent neuron pair, called GABA (gamma
      aminobutyric acid) neurons 1 and 2 (GN1/2), in the lobster Homarus gammarus
      [Cournil et al. (1990) J. Neurocytol., 19, 478-493]. The morphologies of MPN and
      GN1/2 are similar, and both exhibit GABA-immunolabelling. However, unlike MPN,
      GN1/2 does not contain the peptide transmitter proctolin. Instead, GN1/2, but not
      MPN, is immunoreactive for the neuropeptides related to cholecystokinin (CCK) and
      FLRFamide. Nonetheless, GN1/2 excitation of the lobster pyloric rhythm is similar
      to the proctolin-mediated excitation of the crab pyloric rhythm by MPN. In
      contrast, GN1/2 and MPN both use GABA but produce opposite effects on the gastric
      mill rhythm. While MPN stimulation produces a GABA-mediated suppression of the
      gastric rhythm [Blitz & Nusbaum (1999) J. Neurosci., 19, 6774-6783], GN1/2
      activates or enhances gastric rhythmicity. These results highlight the care
      needed when generalizing neuronal organization and function across related
      species. Here we show that the 'same' neuron in different species does not
      contain the same neurotransmitter complement, nor does it exert all of the same
      effects on its postsynaptic targets. Conversely, a different transmitter
      phenotype is not necessarily associated with a qualitative change in the way that
      a modulatory neuron influences target network activity.

PMID- 10947834
TI  - Subthalamic neuron activity related to tremor and movement in Parkinson's
      disease.
AB  - Single cell activity recorded in the subthalamic nucleus (STN) of Parkinson's
      patients and the effect of tremor, passive and voluntary movement upon the same
      cells are described. Three types of cells were distinguished by the pattern of
      discharge: tonic, phasic and rhythmic. They all demonstrated high mean firing
      rates (65, 59 and 69 Hz, respectively). Simultaneous recordings of muscle
      activity and tremor helped in defining cell activity. The implantation of the
      definitive stimulating electrode in the patients was based on the number of STN
      cells related to tremor, active and passive movements (mean = 68%) along the
      track chosen. Cells were related to tremor (n = 21; 11%), modified the discharge
      with differences in the amplitude of tremor (n = 4), and changed the rate and
      pattern when tremor stopped spontaneously or artificially (n = 6). Movement
      related cells (n = 97; 51%) showed a cyclic activity correlated with phases of
      the movement, or modified the firing rate along the performance of the movement.
      Tremor and movement-related cells (n = 11; 6%) revealed an interesting sensory
      motor integrative function.

PMID- 10947835
TI  - A quantitative study of gamma-band activity in human intracranial recordings
      triggered by visual stimuli.
AB  - This paper studies gamma-band responses from two implanted epileptic patients
      during a simple visual discrimination task. Our main aim was to ascertain, in a
      reliable manner, whether evoked (stimulus-locked) and induced (triggered by, but
      not locked to, stimuli) responses are present in intracranial recordings. For
      this purpose, we introduce new methods adapted to detect the presence of gamma
      responses at this level of recording, intermediary between EEG-scalp and
      unicellular responses. The analysis relies on a trial-by-trial time-frequency
      analysis and on the use of surrogate data for statistical testing. We report that
      visual stimulation reliably elicits evoked and induced responses in human
      intracranial recordings. Induced intracranial gamma activity is significantly
      present in short oscillatory bursts (a few cycles) following visual stimulation.
      These responses are highly variable from trial to trial, beginning after 200 ms
      and lasting up to 500 ms. In contrast, intracranial-evoked gamma responses
      concentrate around 100 ms latencies corresponding to evoked responses observed on
      the scalp. We discuss our results in relation to scalp gamma response in a
      similar protocol [Tallon-Baudry et al. (1996) J. Neurosci., 16, 4240-4249] and
      draw some conclusions for bridging the gap between gamma oscillations observed on
      the scalp surface and their possible cortical sources.

PMID- 10947836
TI  - Inflammatory cytokines and related genes are induced in the rat hippocampus by
      limbic status epilepticus.
AB  - Limbic status epilepticus was induced in rats by unilateral 60-min electrical
      stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR
      followed by Southern blot analysis, transcripts of interleukin-1beta, interleukin
      6, interleukin-1 receptor antagonist and inducible nitric oxide synthase were
      significantly increased 2 h after status epilepticus in the stimulated
      hippocampus. Induction was maximal at 6 h for interleukin-1beta (445%),
      interleukin-6 (405%) and tumour necrosis factor-alpha (264%) and at 24 h for
      interleukin-1 receptor antagonist (494%) and inducible nitric oxide synthase
      (432%). In rats with spontaneous seizures (60 days after status epilepticus),
      interleukin-1beta mRNA was still higher than controls (241%). Immunocytochemical
      staining of interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha was
      enhanced in glia with a time-course similar to that of the respective
      transcripts. Sixty days after status epilepticus, interleukin-1beta
      immunoreactivity was increased exclusively in neurons in one third of the
      animals. Multiple intracerebroventricular injections of interleukin-1 receptor
      antagonist (0.5 microg/3 microL) significantly decreased the severity of
      behavioural convulsions during electrical stimulation and selectively reduced
      tumour necrosis factor-alpha content in the hippocampus measured 18 h after
      status epilepticus. Thus, the induction of spontaneously recurring seizures in
      rats involves the activation of inflammatory cytokines and related pro- and anti
      inflammatory genes in the hippocampus. These changes may play an active role in
      hyperexcitability of the epileptic tissue.

PMID- 10947837
TI  - Behavioural changes produced by transgenic overexpression of gamma2L and gamma2S
      subunits of the GABAA receptor.
AB  - Transgenic mice overexpressing either the mouse gamma2L or gamma2S subunit of the
      GABAA receptor were generated in a C57BL/6 J x DBA/2 J mixed background and
      expanded into transgenic lines. Transgenic mice and littermate controls were
      analysed with respect to altered behaviour indicative of anxiety, motor activity
      and acute effects of benzodiazepines and alcohol, as well as with regard to
      altered responses to alcohol withdrawal and acute functional tolerance to
      alcohol. Biochemical tests assessed flunitrazepam- and ethanol-enhanced 36Cl-
      flux stimulated by muscimol in cerebellar and cortical microsacs and [3H]
      flunitrazepam binding to cerebellar membranes. There were no significant
      differences in any of these measures between the transgenic and control mice,
      except in tests of acute functional tolerance to acute injection of ethanol.
      Compared to controls, mice carrying either the gamma2L or gamma2S transgene
      developed significantly less tolerance to the ataxic effects of ethanol. We
      conclude that acute functional tolerance to ethanol is very sensitive to the
      amount of GABAA receptor gamma2 subunit available (regardless of whether it is
      gamma2L or gamma2S) but overexpression of neither subunit isoform alters other
      behavioural and biochemical phenotypes.

PMID- 10947839
TI  - Connexin43 phosphorylation state and intercellular communication in cultured
      astrocytes following hypoxia and protein phosphatase inhibition.
AB  - The effects of hypoxia and phosphatase inhibitors on connexin43 (Cx43)
      phosphorylation state, gap junctional intercellular communication (GJIC) and
      immunolabelling with anti-Cx43 antibodies were investigated in cultured
      astrocytes. Astrocytes contained predominantly phosphorylated forms of Cx43 and
      these underwent dephosphorylation 30 min after hypoxia. This was preceded by a
      77% reduction in GJIC 15 min after hypoxia, indicating that reduced GJIC occurs
      prior to Cx43 dephosphorylation. Hypoxia caused a reduction in punctate
      immunostaining (epitope masking) at cell-cell contacts with one anti-Cx43
      antibody, and increased labelling with another antibody (13-8300) that detects
      only a dephosphorylated form of Cx43. Inhibition of protein phosphatase (PP)-1
      and PP-2A with okadaic acid or calyculin A had little effect on hypoxia-induced
      Cx43 dephosphorylation. Inhibition of PP-2B (calcineurin) with cyclosporin A or
      FK506 reduced Cx43 dephosphorylation and junctional uncoupling seen after
      hypoxia. These results demonstrate that responses of astrocytic Cx43 to hypoxia
      in vitro are similar to those seen after ischaemia in vivo, and that inhibition
      of protein phosphatase protects astrocytes from hypoxia-induced Cx43
      dephosphorylation and junctional uncoupling. In addition, calcineurin may play a
      direct role in the regulation of astrocytic GJIC and Cx43 phosphorylation state.

PMID- 10947838
TI  - Rescue of gamma2 subunit-deficient mice by transgenic overexpression of the GABAA
      receptor gamma2S or gamma2L subunit isoforms.
AB  - The gamma2 subunit is an important functional determinant of GABAA receptors and
      is essential for formation of high-affinity benzodiazepine binding sites and for
      synaptic clustering of major GABAA receptor subtypes along with gephyrin. There
      are two splice variants of the gamma2 subunit, gamma2 short (gamma2S) and gamma2
      long (gamma2L), the latter carrying in the cytoplasmic domain an additional eight
      amino acids with a putative phosphorylation site. Here, we show that transgenic
      mice expressing either the gamma2S or gamma2L subunit on a gamma2 subunit
      deficient background are phenotypically indistinguishable from wild-type. They
      express nearly normal levels of gamma2 subunit protein and [3H]flumazenil binding
      sites. Likewise, the distribution, number and size of GABAA receptor clusters
      colocalized with gephyrin are similar to wild-type in both juvenile and adult
      mice. Our results indicate that the two gamma2 subunit splice variants can
      substitute for each other and fulfil the basic functions of GABAA receptors,
      allowing in vivo studies that address isoform-specific roles in phosphorylation
      dependent regulatory mechanisms.

PMID- 10947840
TI  - Mis3 with a conserved RNA binding motif is essential for ribosome biogenesis and
      implicated in the start of cell growth and S phase checkpoint.
AB  - BACKGROUND: In normal somatic cell cycle, growth and cell cycle are properly
      coupled. Although CDK (cyclin-dependent kinase) activity is known to be essential
      for cell cycle control, the mechanism to ensure the coupling has been little
      understood. RESULTS: We here show that fission yeast Mis3, a novel evolutionarily
      highly conserved protein with the RNA-interacting KH motif, is essential for
      ribosome RNA processing, and implicated in initiating the cell growth. Growth
      arrest of mis3-224, a temperature sensitive mutant at the restrictive
      temperature, coincides with the early G2 block in the complete medium or the G1/S
      block in the release from nitrogen starvation, reflecting coupling of cell growth
      and division. Genetic interactions indicated that Mis3 shares functions with cell
      cycle regulators and RNA processing proteins, and is under the control of Dsk1
      kinase and PP1 phosphatase. Mis3 is needed for the formation of 18S ribosome RNA,
      and may hence direct the level of proteins required for the coupling. One such
      candidate is Mik1 kinase. mis3-224 is sensitive to hydroxyurea, and the level of
      Mik1 protein increases during replication checkpoint in a manner dependent upon
      the presence of Mis3 and Cds1. CONCLUSIONS: Mis3 is essential for ribosome
      biogenesis, supports S phase checkpoint, and is needed for the coupling between
      growth and cell cycle. Whether Mis3 interacts solely with ribosomal precursor RNA
      remains to be determined.

PMID- 10947841
TI  - Ebp2p, yeast homologue of a human protein that interacts with Epstein-Barr virus
      nuclear antigen 1, is required for pre-rRNA processing and ribosomal subunit
      assembly.
AB  - BACKGROUND: A defect in the secretory pathway causes the transcriptional
      repression of both rRNA and ribosomal protein genes in Saccharomyces cerevisiae,
      suggesting a coupling of ribosome synthesis and plasma membrane synthesis. Rrs1p,
      an essential nuclear protein, is required for the secretory response. RESULTS:
      EBP2, encoding the yeast homologue of a human protein that interacts with Epstein
      Barr virus Nuclear Antigen 1, was cloned in a two-hybrid screen using RRS1 as a
      bait. The rrs1-1 mutation, which produces Rrs1p without the C-terminal half and
      causes a defect in the secretory response, almost abolished the interaction with
      Ebp2p. Ebp2p is essential for growth and is mainly localized in the nucleolus.
      The effects of Ebp2p depletion on ribosome biogenesis is quite similar to that of
      Rrs1p depletion; in the Ebp2p-depleted cells, the rate of pre-rRNA processing is
      slower, and significantly less mature 25S rRNA is produced compared to those in
      wild-type cells. The polysome pattern indicates that Ebp2p-depletion causes a
      decrease of 80S monosomes and polysomes, an accumulation of 40S subunits, and the
      appearance of half-mer polysomes. CONCLUSIONS: Ebp2p is required for the
      maturation of 25S rRNA and 60S subunit assembly. Ebp2p may be one of the target
      proteins of Rrs1p for executing the signal to regulate ribosome biogenesis.

PMID- 10947842
TI  - Tuning of the porin expression under anaerobic growth conditions by his-to-Asp
      cross-phosphorelay through both the EnvZ-osmosensor and ArcB-anaerosensor in
      Escherichia coli.
AB  - BACKGROUND: Widespread bacterial signal transduction circuits are generally
      referred to as 'two-component systems' or 'histidine (His)-to-aspartate (Asp)
      phosphorelays.' In Escherichia coli, as many as 30 distinct His-to-Asp
      phosphorelay signalling pathways operate in response to a wide variety of
      environmental stimuli, such as medium osmolarity and anaerobiosis. In this
      regard, it is of interest whether or not some of them together constitute a
      network of signalling pathways through a physiologically relevant mechanism
      (often referred to as 'cross-regulation'). We have addressed this issue, with
      special reference to the osmo-responsive EnvZ and anaero-responsive ArcB
      phosphorelay signalling pathways in E. coli. RESULTS: Under standard aerobic
      growth conditions, it is well known that the osmoregulatory profile of the outer
      membrane porins (OmpC and OmpF) is mainly regulated by the EnvZ-OmpR phosphorelay
      system in response to medium osmolarity. In this study, it was found that, under
      anaerobic growth conditions, E. coli cells exhibit a markedly altered expression
      profile of OmpC and OmpF This profile was significantly different from that
      observed for the cells grown aerobically. Results from extensive genetic studies
      showed that, under such anaerobic growth conditions, the arcB gene encoding the
      anaero-sensory His-kinase appears to be an auxiliary genetic determinant that
      regulates the expression profile of porins. We then provided several lines of in
      vivo and in vitro evidence, which taken together, supported the following
      conclusions. CONCLUSIONS: Under anaerobic growth conditions, porin expression is
      tuned not only by the authentic osmo-resposive EnvZ sensor, but also by the
      anaero-responsive ArcB sensor, in an OmpR-dependent manner. It is suggested that
      such ArcB-mediated cross-regulation plays a physiological role by integrating
      anaerobic respiratory signals into the porin regulation in E. coli anaerobiosis.
      The proposed model is a clear example of the interplay of two distinct His-to-Asp
      phosphorelay signalling pathways.

PMID- 10947843
TI  - Phosphorylation of ERM proteins at filopodia induced by Cdc42.
AB  - BACKGROUND: ERM (ezrin, radixin, and moesin) proteins function as membrane
      cytoskeletal linkers, and are known to be localized at filopodia and microvilli
      like structures. We have shown that Rho-associated kinase (Rho
      kinase)/ROKalpha/ROCK II phosphorylates moesin at Thr-558 at the lower stream of
      Rho, and the phosphorylation is crucial to the formation of microvilli-like
      structures (Oshiro, N., Fukata, Y. & Kaibuchi, K. (1998) Phosphorylation of
      moesin by Rho-associated kinase (Rho-kinase) plays a crucial role in the
      formation of microvilli-like structures. J. Biol. Chem. 273, 34663- 34666).
      However, the role of ERM proteins in the formation of filopodia is less well
      characterized. RESULTS: Here we examined the phosphorylation state of ERM during
      filopodia formation induced by Cdc42 using the antibody recognizing ERM proteins
      phosphorylated at COOH (C)-terminal threonine. When NIH 3T3 cells were
      transfected with constitutively active Cdc42 (Cdc42V12), filopodia formation was
      induced and phosphorylation of ERM at C-terminal threonine was observed at the
      tip of filopodia, while the phosphorylation levels of ERM were lower and
      phosphorylated ERM was distributed throughout the cytoplasm in the control cells.
      We also showed that Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK)
      which has been identified as an effector of Cdc42, phosphorylated moesin at C
      terminal threonine in a cell-free system. Coexpression of the dominant negative
      form of MRCK inhibited both the formation of filopodia and accumulation of C
      terminal threonine-phosphorylated ERM proteins at filopodia induced by Cdc42V12.
      CONCLUSION: The formation of filopodia induced by Cdc42 is accompanied by
      phosphorylation of ERM proteins, and MRCK is a candidate for the kinase that
      phosphorylates ERM proteins at filopodia.

PMID- 10947844
TI  - Importance of spatial activation of Cdc42 and rac small G proteins by frabin for
      microspike formation in MDCK cells.
AB  - BACKGROUND: Frabin is an actin filament (F-actin)-binding protein that shows
      GDP/GTP exchange activity for Cdc42 small G protein (Cdc42). Frabin furthermore
      induces indirect activation of Rac small G protein (Rac) in intact cells. We have
      recently shown that in nonepithelial cells, frabin induces the formation of both
      filopodia- and lamellipodia-like processes through the activation of Cdc42 and
      Rac, respectively. In epithelial cells such as MDCK cells, Cdc42 and Rac regulate
      cell-cell adherens junctions (AJs) via the accumulation of F-actin and E
      cadherin, although neither Cdc42 nor Rac induces the formation of filopodia or
      lamellipodia. In this study, we have examined the effects of frabin on the
      reorganization of the actin cytoskeleton in MDCK cells. RESULTS: Frabin induces
      the formation of microspikes at the basal area of the lateral membranes through
      the activation of Cdc42 and Rac in MDCK cells, although a dominant active mutant
      of Cdc42 or Rac alone, or both, did not induce the formation of microspikes.
      Furthermore, frabin weakly increased the accumulation of F-actin and E-cadherin
      at cell-cell AJs and the formation of stress fibres through the activation of
      Cdc42 and Rac, under conditions where the dominant active mutant of Cdc42 or Rac
      markedly showed these effects. The Cdc42- and Rac-induced formation of stress
      fibres was dependent on the activation of Rho small G protein. CONCLUSION: These
      results indicate that the frabin-dependent spatial activation of Cdc42 and Rac is
      important for the formation of microspikes.

PMID- 10947845
TI  - Molecular mechanism of a cross-talk between oestrogen and growth factor
      signalling pathways.
AB  - Oestrogen (E2) plays significant roles in variety of biological events such as
      the development and maintenance of female reproductive organs, bone and lipid
      metabolisms. More recently, from study of knock-out mice deficient in oestrogen
      receptor (ER) alpha and ERbeta it turned out that normal spermatogenesis requires
      the E2 actions. Furthermore, this female steroid hormone is also well known to be
      deeply involved in many pathophysiological events such as osteoporosis and cancer
      development in female reproductive organs. It is particularly well known that
      most breast cancer is dependent on E2 in its development. Such E2 actions are
      thought to be mediated through two subtypes of ERs. Growth factors have been
      shown to synergize in this E2 signalling pathway, although the actual molecular
      mechanism largely remains unknown. Recently, we found that the MAP kinase
      activated by growth factors phosphorylates the Ser118 residue of the human
      ERalpha A/B domain and this phosphorylation potentiates the N-terminal
      transactivation function (AF-1) of human ERalpha, indicating the possible
      molecular mechanism of a novel cross-talk between E2 and growth factor signalling
      pathways. More recently, we have identified a coactivator associating with the
      hERalpha AF-1 in a MAPK-mediated phosphorylation-dependent manner. In this
      review, the molecular mechanism of this cross-talk is discussed in terms of the
      transactivation function of ERs, and their coactivators.

PMID- 10947846
TI  - Significant activity of a modified ribozyme with N7-deazaguanine at g10.1: the
      double-metal-ion mechanism of catalysis in reactions catalysed by hammerhead
      ribozymes.
AB  - BACKGROUND: Several reports have appeared recently of experimental evidence for a
      double-metal-ion mechanism of catalysis in reactions catalysed by hammerhead
      ribozymes. In one case, hammerhead ribozyme-mediated cleavage was analysed as a
      function of the concentration of La3+ ions in the presence of a fixed
      concentration of Mg2+ ions so that the role of metal ions that are directly
      involved in the cleavage reaction could be monitored. The resultant bell-shaped
      curve for activation of cleavage was used to support the proposed double-metal
      ion mechanism of catalysis. However, other studies have demonstrated that the
      binding of a metal ion (the most conserved P9 metal ion) to the pro-Rp oxygen (P9
      oxygen) of the phosphate moiety of nucleotide A9 and to the N7 of nucleotide
      G10.1 is critical for efficient catalysis, despite the large distance (
      approximately 20 A) between the P9 metal ion and the labile phosphodiester group
      in the ground state. In fact, it was demonstrated that an added Cd2+ ion binds
      first to the pro-Rp phosphoryl P9 oxygen but not with the pro-Rp phosphoryl
      oxygen at the cleavage site. RESULTS: In earlier discussions, it was difficult to
      completely exclude the possibility that La3+ ions might have replaced the P9
      metal ion and, as a result, created conditions represented by the bell-shaped
      curve. In order to clarify this situation, we examined a chemically synthesized
      hammerhead ribozyme (7-deaza-R34) that included a minimal modification, namely,
      an N7-deazaguanine residue in place of G10.1. We compared the kinetic properties
      of this ribozyme with those of the parental ribozyme (R34). Kinetic analysis
      revealed that, unlike the cases of added Cd2+ ions, the added La3+ ions did not
      replace the pre-existing P9 metal ion, and that the replacement of N7 by C7 at
      G10.1 reduced the catalytic activity to a limited extent. This result indicates
      that the binding of a Mg2+ ion to N7 at G10.1 is catalytically important but not
      indispensable. Most importantly, 7-deaza-R34 also yielded a bell-shaped curve
      upon addition of La3+ ions to the reaction mixture. CONCLUSIONS: Since the data
      based on our experiments with 7-deaza-R34 are completely free from potential
      artefacts, due to the binding of a La3+ ion to N7 at G10.1, our results, that 7
      deaza-R34 yielded a bell-shaped curve following the addition of La3+ ions to the
      Mg2+-background reaction mixture, strongly supports the proposal that a double
      metal-ion mechanism is operative in the cleavage reaction which is catalysed by
      hammerhead ribozymes.

PMID- 10947847
TI  - Two types of localization of the DNA-binding proteins within the Escherichia coli
      nucleoid.
AB  - BACKGROUND: The genome DNA of Escherichia coli is folded into the nucleosome-like
      structure, often called a nucleoid, by the binding of several DNA-binding
      proteins. We previously determined the specificity and affinity of DNA-binding
      for 12 species of the E. coli DNA-binding protein, and their intracellular
      concentrations at various growth phases. The intracellular localization of these
      proteins in E. coli could be predicted from these data, but no attempt has been
      made thus far to directly observe the intracellular distribution of the DNA
      binding proteins. RESULTS: The intracellular localization in Escherichia coli of
      10 species of the nucleoid-associated protein, three components of the
      transcripton apparatus, and three components of the translation machinery was
      investigated by indirect immuno-fluorescence microscopy. The DNA-binding proteins
      could be classified into two groups. The group-I proteins, including the major
      nucleoid-structural proteins, H-NS, HU, IHF, StpA and Dps, are distributed
      uniformly within the entire nucleoid. In contrast, the group-II proteins, which
      are presumed to possess regulatory activities of DNA functions accumulate at
      specific loci within the nucleoid, forming 2 (SeqA), 3-4 (CbpA and CbpB) and 6-10
      (Fis and IciA) immuno-stained dots. Each immuno-stained dot may represent either
      the association of a hundred to one thousand molecules of each DNA-binding
      protein at a specific locus of the genome DNA or the assembly of protein
      associated DNA segments from different domains of the folded genome. Both the RNA
      polymerase core enzyme and the sigma70 subunit are mainly associated with the
      nucleoid, but the anti-sigma70 factor (Rsd) appears to be accumulated at the
      boundary between the nucleoid and the cytosol in the stationary-phase cells. Here
      we show that the majority of Hfq is present in cytoplasm together with ribosomal
      proteins L7/L12 and RMF. CONCLUSION: The DNA-binding proteins of E. coli could be
      classified into two groups. One group proteins was distributed uniformly within
      the nucleoid, but the other group of proteins showed an irregular distribution,
      forming immuno-stained spots or clumps.

PMID- 10947848
TI  - Requirement of transfer-messenger RNA for the growth of Bacillus subtilis under
      stresses.
AB  - BACKGROUND: Bacterial transfer-messenger RNA (tmRNA, 10Sa RNA) is involved in a
      trans-translation reaction which contributes to the degradation of incompletely
      synthesized peptides and to the recycling of stalled ribosomes. However, its
      physiological role in the cell remains elusive. In this study, an efficient
      system for controlling the expression of the gene for tmRNA (ssrA), as well as a
      tmRNA gene-defective strain (ssrA:cat), were constructed in Bacillus subtilis.
      The effects of tmRNA on the growth of the cells were investigated under various
      physiological culture conditions using these strains. RESULTS: The cells were
      viable in the absence of ssrA expression under the usual culture conditions.
      However, the growth rate of cells without tmRNA expression, relative to that of
      the expressed cells, decreased with elevating temperature (> 45 degrees C), and
      at 52 degrees C, the highest temperature for growth of the wild-type, cells grew
      depending on the expression level of tmRNA. Furthermore, the transcription level
      of the ssrA from the authentic promoter at a high temperature (51 degrees C) was
      about 10-fold higher than that at a lower temperature (37 degrees C). tmRNA
      dependent growth and an increase in tmRNA amount were also observed in cells
      under other stresses, such as high concentrations of ethanol or cadmium chloride.
      It is also shown that alanylated tmRNA rather than tmRNA-mediated proteolysis is
      required for growth at high temperature. CONCLUSION: The expression of tmRNA gene
      (ssrA) is required for the efficient growth of B. subtilis under several strong
      stresses. The transcription of ssrA increases under several stressful conditions,
      suggesting that it is a stress-response gene. Alanyl-tmRNA, probably via its
      ability of recycling stalled ribosomes via trans-translation, is involved in the
      stress tolerance of bacteria.

PMID- 10947849
TI  - Ribonuclease H attack of leukaemic fused transcripts AML1-MTG8 (ETO) by DNA/RNA
      chimeric hammerhead ribozymes.
AB  - BACKGROUND: Catalytic anti-sense oligonucleotides might be useful tools for
      controlling specific gene expression. However, to obtain effective
      oligonucleotides of the desired function in vivo is still a difficult task.
      RESULTS: To evaluate the usefulness of synthesized DNA/RNA hammerhead ribozymes
      targeting AML1-MTG8 (ETO) leukaemic fusion transcripts in vivo, we analysed their
      effects on cell growth and the mechanism of action using isolated cell nuclei.
      These ribozymes inhibited the growth of leukaemic cell lines expressing the AML1 
      MTG8 and degraded AML1-MTG8 mRNA in isolated nuclei of these cells. However, the
      reactions gave rise to additional cleavage products. Systematic cleavage analyses
      using an anti-sense oligonucleotide array revealed that the cleavage was induced
      by endogenous RNase H at specific sites, in accordance with their calculated
      melting temperature (Tm) values. With suppression of RNase H by sulfhydryl
      agents, the DNA/RNA ribozyme had a ribozyme catalytic activity. In addition, the
      ribozymes and anti-sense oligonucleotides suppressed the AML1-MTG8 protein in the
      leukaemic cells. CONCLUSIONS: The DNA/RNA ribozymes inhibited cell growth
      primarily via anti-sense effects, the main role of which was the activation of
      RNase H-digestion by their DNA arms. In addition, the isolated nuclei provided a
      useful assay system for modelling in vivo conditions for the quantitative
      evaluation of anti-sense/ribozyme activity.

PMID- 10947850
TI  - The paternal methylation imprint of the mouse H19 locus is acquired in the
      gonocyte stage during foetal testis development.
AB  - BACKGROUND: Germline-specific differential DNA methylation that persists through
      fertilization and embryonic development is thought to be the 'imprint'
      distinguishing the parental alleles of imprinted genes. If such methylation is to
      work as the imprinting mechanism, however, it has to be reprogrammed following
      each passage through the germline. Previous studies on maternally methylated
      genes have shown that their methylation imprints are first erased in primordial
      germ cells (PGCs) and then re-established during oocyte growth. RESULTS: We have
      examined the timing of the reprogramming of the paternal methylation imprint of
      the mouse H19 gene during germ cell development. In both male and female PGCs,
      the paternal allele is partially methylated whereas the maternal allele is
      unmethylated. This partial methylation is completely erased in the female
      germline by entry into meiosis, establishing the oocyte methylation pattern. In
      the male germline, both alleles become methylated, mainly during the gonocyte
      stage, establishing the sperm methylation pattern. CONCLUSION: The paternal
      methylation imprint of H19 is established in the male germline and erased in the
      female germline at specific developmental stages. The identification of the
      timings of the methylation and demethylation should help to identify and
      characterize the biochemical basis of the reprogramming of imprinting.

PMID- 10947851
TI  - Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells
      and astrocytes: role of upstream stimulatory factor.
AB  - BACKGROUND: Mutations in the myocilin (MYOC)/TIGR gene are responsible for
      autosomal-dominant juvenile primary open-angle glaucoma (POAG). In patients with
      non-autosomal-dominant POAG, such mutations are rare, but the expression of
      MYOC/TIGR in the trabecular meshwork (TM) of the eye is considerably higher than
      in normals. We performed transfection, DNAse I footprinting, mutagenesis and
      electrophoretic mobility shift assays (EMSA) to identify elements responsible for
      the basal transcription of MYOC/TIGR in TM cells and astrocytes. RESULTS: DNAse I
      footprinting experiments of the human MYOC/TIGR promoter showed a major protected
      area between nt -106 to -77, which was not conserved in the homologous region of
      the mouse myoc/tigr promoter. In addition, the TATA-box was protected, as well as
      at least three downstream sites, including an AP-1-like sequence. Deletion of the
      -106 to -77 region caused a substantial loss of functional promotor activity in
      all cell types. Site-directed mutagenesis and EMSA experiments revealed the
      presence of two regulatory elements in the -106 to -77 region. Each of these cis
      elements is essential for minimal promoter activity. The 5'-half of the region
      contains a sequence with similarities to NF-kappaB-related sites, however,
      binding of NF-kappaB could not be confirmed by EMSA. The 3'-half contains a
      canonical E-box sequence. EMSA experiments showed that the upstream regulatory
      factor (USF) was binding to the E-box sequence and that the binding can be
      supershifted by specific antibodies. CONCLUSIONS: Several DNA-protein binding
      elements contribute to a transcription of MYOC/TIGR, and USF is critically
      required for its basal transcription in trabecular meshwork cells and astrocytes.

PMID- 10947852
TI  - MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing
      DNMT1 at the replication foci in late S phase.
AB  - BACKGROUND: In vertebrates and plants, DNA methylation is one of the major
      mechanisms regulating gene expression. Recently, a family of methyl-CpG-binding
      proteins has been identified, and some members, such as MeCP2 and MBD2, were
      shown to mediate gene repression by recruiting histone deacetylase complexes to
      methylated genes. However, the function of another member of this family, MBD3,
      remained elusive. RESULTS: It was shown that MBD2 and MBD3 form homo- and hetero
      dimers (or multimers) in vitro and in vivo. Significantly, the MBD2-MBD3 complex
      showed an affinity to hemi-methylated DNAs, a property that has never been
      reported with any member of the family proteins. MBD2 and MBD3 were co-localized
      with DNMT1 at replication foci in 293 cell nuclei at late S phase. Moreover, by a
      co-immunoprecipitation experiment, DNMT1 was shown to form a complex with MBD2
      and MBD3. Finally, the abundance of MBD3 was highest in the late S phase when the
      DNMT1 is also most abundant, whereas the MBD2 level was largely constant
      throughout the cell cycle. CONCLUSIONS: The results suggest that MBD3 may play an
      important role in the S phase. We hypothesize that the MBD2-MBD3 complex
      recognizes hemi-methylated DNA concurrent with DNA replication and recruits
      histone deacetylase complexes, as well as DNMT1, to establish and/or maintain the
      transcriptionally repressed chromatin.

PMID- 10947853
TI  - How to establish a lasting relationship with your host: lessons learned from
      Mycobacterium spp.
AB  - Mycobacterium spp. enjoy an intracellular lifestyle that is fatal to most
      microorganisms. Bacilli persist and multiply within mononuclear phagocytes in the
      face of defences ranging from toxic oxygen and nitrogen radicals, acidic
      proteases and bactericidal peptides. Uptake of Mycobacterium by phagocytes
      results in the de novo formation of a phagosome, which is manipulated by the
      pathogen to accommodate its needs for intracellular survival and replication. The
      present review describes the intracellular compartment occupied by Mycobacterium
      spp. and presents current ideas on how mycobacteria may establish this niche,
      placing special emphasis on the involvement of mycobacterial cell wall lipids.

PMID- 10947854
TI  - Life on the inside: probing mycobacterium tuberculosis gene expression during
      infection.
AB  - The identification of Mycobacterium tuberculosis genes specifically expressed
      during infection is a key step in understanding mycobacterial pathogenesis. Such
      genes most likely encode products required for survival within the host and for
      progressive infection. Recent advances in mycobacterial genetics have permitted
      the development of new techniques and the adaptation of existing methods to
      analyse mycobacterial in vivo gene expression and virulence. This has revealed a
      subset of M. tuberculosis genes that are differentially expressed during
      infection and has demonstrated that a number of components contribute to the
      virulence of the organism. This information is expected to provide new strategies
      to prevent tuberculosis infection, new targets for antimicrobial therapy and new
      insights into the infectious process.

PMID- 10947855
TI  - Interaction of dendritic cells with mycobacteria: where the action starts.
AB  - Dendritic cells (DC) are the major antigen-presenting cells in the induction of
      cellular responses to intracellular pathogens, such as mycobacteria. Recent
      studies have shown that they also play a critical role in the regulation of
      immune responses. The interaction of DC with microbial antigens may be the
      controlling factor in the development of a Th1-orientated protective immunity.
      Analysis of the innate response of DC to mycobacteria and the involvement of the
      DC receptors in antigen recognition have highlighted the pivotal role of these
      cells in T-cell activation. Mycobacteria-infected DC have an enhanced capacity to
      release pro-inflammatory cytokines and chemokines and are potent inducers of
      interferon-gamma-producing cells in vivo. Therefore, DC manipulation for maximal
      antigen presentation and Th1 cytokine production may form the basis of a new
      generation of vaccines, with improved efficacy against mycobacterial infections.

PMID- 10947856
TI  - Role of CD8 T cells in mycobacterial infections.
AB  - The interaction between IFN-gamma-secreting CD4+ T cells and macrophages has long
      been established as integral in the protective immune response against
      tuberculosis. More recently, evidence from murine experiments and human studies
      has begun to demonstrate an essential role for MHC class I restricted CD8+ T
      cells in this immune response. CD8+ T cells can produce the protective cytokines
      IFN-gamma and TNF-alpha in addition to their classical cytolytic functions.
      However, the exact protective mechanisms and antigens recognized by these
      important cells remain poorly characterized.

PMID- 10947857
TI  - Restraining mycobacteria: role of granulomas in mycobacterial infections.
AB  - The generation of prolonged immunity to Mycobacterium tuberculosis requires not
      only an antigen-specific IFN-gamma-producing T cell response, including both CD4
      and CD8 T cells, but also the generation of protective granulomatous lesions,
      whereby the close apposition of activated T cells and macrophages acts to contain
      bacterial growth. The importance of the granulomatous lesion in controlling this
      immune response and in limiting both tissue damage and bacterial dissemination
      has been considered a secondary event but, as the present review illustrates, is
      no less important in surviving mycobacterial infection than an antigen-specific T
      cell response. The formation of a protective granuloma involves the orchestrated
      production of a host of chemokines and cytokines, the upregulation of their
      receptors along with upregulation of addressins, selectins and integrins to
      coordinate the recruitment, migration and retention of cells to and within the
      granuloma. In the present review, the principal components of the protective
      response are outlined and the role of granuloma formation and maintenance in
      mediating prolonged containment of mycobacteria within the lung is addressed.

PMID- 10947859
TI  - Novel mechanisms in the immunopathogenesis of leprosy nerve damage: the role of
      Schwann cells, T cells and Mycobacterium leprae.
AB  - The major complication of reversal (or type 1) reactions in leprosy is peripheral
      nerve damage. The pathogenesis of nerve damage remains largely unresolved. In
      situ analyses suggest an important role for type 1 T cells. Mycobacterium leprae
      is known to have a remarkable tropism for Schwann cells that surround peripheral
      axons. Reversal reactions in leprosy are often accompanied by severe and
      irreversible nerve destruction and are associated with increased cellular immune
      reactivity against M. leprae. Thus, a likely immunopathogenic mechanism of
      Schwann cell and nerve damage in leprosy is that infected Schwann cells process
      and present antigens of M. Leprae to antigen-specific, inflammatory type 1 T
      cells and that these T cells subsequently damage and lyse infected Schwann cells.
      Previous studies using rodent CD8+ T cells and Schwann cells have revealed
      evidence for the existence of such a mechanism. Recently, a similar role has been
      suggested for human CD4+ T cells. These cells may be more important in causing
      leprosy nerve damage in vivo, given the predilection of M. leprae for Schwann
      cells and the dominant role of CD4+ serine esterase+ Th1 cells in leprosy
      lesions. Antagonism of molecular interactions between M. leprae, Schwann cells
      and inflammatory T cells may therefore provide a rational strategy to prevent
      Schwann cell and nerve damage in leprosy.

PMID- 10947858
TI  - New tuberculosis vaccines based on attenuated strains of the Mycobacterium
      tuberculosis complex.
AB  - The world urgently needs a better tuberculosis vaccine. Bacille Calmette-Guerin
      (BCG), an attenuated strain of Mycobacterium bovis, has been very widely used as
      a vaccine for many years but has had no major effect on reducing the incidence of
      tuberculosis. A number of alternative living and non-living vaccines are being
      investigated. Live vaccine candidates include genetically modified forms of BCG,
      genetically attenuated strains of the Mycobacterium tuberculosis complex and
      genetically engineered vaccinia virus and Salmonella strains. Non-living vaccine
      candidates include killed mycobacterial species, protein subunits and DNA
      vaccines. One requirement for acceptance of any new vaccine will be a favourable
      comparison of the protection it induces relative to BCG in a range of animal
      models, some of which may need further development. Molecular genetic techniques
      are now available that enable production of live attenuated strains of the M.
      tuberculosis complex with vaccine potential. In the first of two broadly
      different approaches that are being used, large numbers of mutants are produced
      by transposon mutagenesis or illegitimate recombination and are screened for
      properties that correlate with attenuation. In the second approach, putative
      genes that may be required for virulence are identified and subsequently
      inactivated by allelic exchange. In both approaches, mutants that are attenuated
      need to be identified and subsequently tested for their vaccine efficacy in
      animal models. Many mutants of the M. tuberculosis complex have now been produced
      and the vaccine properties of a substantial number will be assessed in the next 3
      years.

PMID- 10947860
TI  - Diverse intracellular signalling systems used by growth hormone-releasing hormone
      in regulating voltage-gated Ca2+ or K channels in pituitary somatotropes.
AB  - Influx of Ca2+ via Ca2+ channels is the major step triggering exocytosis of
      pituitary somatotropes to release growth hormone (GH). Voltage-gated Ca2+ and K+
      channels, the primary determinants of the influx of Ca2+, are regulated by GH
      releasing hormone (GHRH) through G-protein-coupled intracellular signalling
      systems. Using whole-cell patch-clamp techniques, the changes of the Ca2+ and K+
      currents in primary cultured ovine and human somatotropes were recorded. Growth
      hormone-releasing hormone (10 nmol/L) increased both L- and T-type voltage-gated
      Ca2+ currents. Inhibition of the cAMP/protein kinase A (PKA) pathway by either Rp
      cAMP or H89 blocked this increase in both L- and T-type Ca2+ currents. Growth
      hormone-releasing hormone also decreased voltage-gated transient (IA) and delayed
      rectified (IK) K+ currents. Protein kinase C (PKC) inhibitors, such as calphostin
      C, chelerythrine or downregulation of PKC, blocked the effect of GHRH on K+
      currents, whereas an acute activation of PKC by phorbol 12, 13-dibutyrate (1
      micromol/L) mimicked the effect of GHRH. Intracellular dialysis of a specific PKC
      inhibitor (PKC19-36) also prevented the reduction in K+ currents by GHRH. It is
      therefore concluded that GHRH increases voltage-gated Ca2+ currents via cAMP/PKA,
      but decreases voltage-gated K+ currents via the PKC signalling system. The GHRH
      induced alteration of Ca2+ and K+ currents augments the influx of Ca2+, leading
      to an increase in [Ca2+]i and the GH secretion.

PMID- 10947861
TI  - Signal transduction and white cell maturation via extracellular ATP and the P2Y11
      receptor.
AB  - Extracellular ATP promotes a wide range of physiological effects in many tissues.
      Of particular interest is the effect of ATP on leukaemia-derived HL-60 and NB4
      cell lines, which are induced to mature to neutrophil-like cells. The
      differentiation process appears to be mediated by ATP binding to a cell-surface
      purinergic P2Y receptor, resulting in the stimulation of adenylyl cyclase,
      elevation of cAMP levels and activation of protein kinase A. In 1997, a novel ATP
      selective P2Y receptor, P2Y11, was cloned and shown to be linked to both cAMP and
      Ca2+ signalling pathways. The pharmacological profile of ATP analogues used by
      P2Y11 for cAMP production in transfected cells is reviewed in the present paper
      and shown to be closely similar to the profiles for cAMP production and
      differentiation of myeloblastic HL-60 cells and promyelocytic NB4 cells, both of
      which express P2Y11. Additional data are provided showing that HL-60 mature to
      neutrophil-like cells in response to extracellular ATP, as measured by
      upregulation of the N-formyl peptide receptor, N-formyl peptide-mediated actin
      polymerization and superoxide production. It is proposed that P2Y11 is
      responsible for the ATP-mediated differentiation of these cells lines and that
      this receptor may play a role in the maturation of granulocytic progenitors in
      the bone marrow.

PMID- 10947863
TI  - Nuclear and cytoskeletal translocation and localization of heterotrimeric G
      proteins.
AB  - Heterotrimeric GTP-binding proteins (G-proteins) are involved in a diverse array
      of signalling pathways. They are generally thought to be membrane-bound proteins,
      which disassociate on receptor activation and binding of GTP. A model to explain
      this has been proposed, which is often described as 'the G-protein cycle'. The 'G
      protein cycle' is discussed in the present paper in relation to evidence that now
      exists regarding the non- membranous localization of G-proteins. Specifically,
      the experimental evidence demonstrating association of G-proteins with the
      cytoskeleton and the nucleus, and the mechanisms by which G-proteins translocate
      to these sites are reviewed. Furthermore, the possible effector pathways and the
      physiological function of G-proteins at these sites are discussed.

PMID- 10947862
TI  - Studying heterotrimeric G-protein-linked signal transduction using replication
      deficient adenoviruses.
AB  - Plasma membrane-spanning G-protein-linked receptors transduce approximately 60%
      of all extracellular stimuli in higher animals. Many G-protein-linked receptor
      pathways are yet to be elucidated, with the receptor, G-protein or effector
      system as yet unidentified. In addition, many fundamental issues pertaining to G
      protein signalling remain unresolved, such as the factors governing the
      specificity of G-protein receptor coupling and the control of signal amplitude in
      response to G-protein activation. In order to address some of these issues, the
      use of replication-deficient adenoviruses as gene transfer vectors for
      investigations of G-protein signalling has been developed, facilitating
      dissection of G-protein-linked signal transduction pathways in an extensive range
      of cultured cells, as well as in vivo. The present review focuses on the
      versatility and utility of adenoviruses for the investigation of signalling by
      heterotrimeric G-proteins and explores some of the recent advances in adenoviral
      technology as they relate to the study of signal transduction.

PMID- 10947864
TI  - Nuclear and nucleolar localization of parathyroid hormone-related protein.
AB  - Parathyroid hormone-related protein (PTHrP) was first discovered as the factor
      causing hypercalcaemia produced by solid tumours frequently associated with the
      head and neck, breast, lung and kidney. The homology of its amino-terminus to
      parathyroid hormone (PTH; eight of the first 13 residues are identical), enables
      it to share the same receptor and perform similar biological functions to PTH.
      The sequences of PTHrP C-terminal to its PTH-like region confer functions such as
      transplacental calcium transport, renal bicarbonate excretion and in vitro
      osteoclast inhibition. Recent findings have shown that PTHrP is a
      nuclear/nucleolar protein in certain tissues and that this localization is cell
      cycle-regulated, mediated by the middle portion of the molecule, and involves the
      nuclear import receptor importin beta1. The present review discusses what is
      known about the pathway by which PTHrP localizes to the nucleus/nucleolus and the
      putative roles it may have there.

PMID- 10947865
TI  - Seeing is believing: recent trends in the measurement of Ca2+ in subcellular
      domains and intracellular organelles.
AB  - The role of Ca2+ in the regulation of the cell cycle has been investigated mostly
      in studies assessing global cytosolic free Ca2+. Recent studies, however, have
      used unique techniques to assess Ca2+ in subcellular organelles, such as
      mitochondria, and in discrete regions of the cytoplasm. These studies have used
      advanced fluorescence digital imaging techniques and Ca2+-sensitive fluorescence
      probes, and/or targeting of Ca2+-sensitive proteins to intracellular organelles.
      The present review describes the results of some of these studies and the
      techniques used. The novel techniques used to measure Ca2+ in microdomains and
      intracellular organelles are likely to be of great use in future investigations
      assessing Ca2+ homeostasis during the cell cycle.

PMID- 10947867
TI  - Chemokine and cytokine cooperativity: eosinophil migration in the asthmatic
      response.
AB  - Eosinophils play a central role in the pathophysiology of allergic disease. The
      mechanisms that regulate eosinophil migration are complex; however, chemokines
      and cytokines produced in both the early and late phases of the asthmatic
      response appear to cooperate in eosinophil recruitment. In particular, there
      exists a unique synergy between eotaxin and IL-5. The role of chemokine/cytokine
      cooperativity has been investigated in the extracellular matrix, adhesion
      molecule/integrin interactions, receptor polarization and aggregation and the
      convergence and divergence of intracellular signalling pathways. Understanding
      the mechanisms whereby eosinophils migrate will allow the development of specific
      therapeutic strategies aimed at attenuating specific components of the allergic
      response.

PMID- 10947866
TI  - Insulin induces epidermal growth factor (EGF) receptor clustering and potentiates
      EGF-stimulated DNA synthesis in swiss 3T3 cells: a mechanism for costimulation in
      mitogenic synergy.
AB  - In many cellular systems, activation with more than one ligand can produce a
      cellular response that is greater than the sum of the individual responses to the
      ligands. This synergy is sometimes referred to as coactivation. In Swiss 3T3
      fibroblasts, activation of the epidermal growth factor (EGF) receptor produces a
      weak induction of DNA synthesis. Insulin has no stimulatory effect on this
      response. However, in combination, EGF and insulin synergize to cause a large
      induction of S phase. The underlying cellular biochemistry of this effect has
      been examined. The data indicate that phospholipase C activation is a major
      component of agonist-induced DNA synthesis. In contrast, activation of p70 S6
      kinase by single agonists was inversely related to their ability to stimulate DNA
      synthesis. Therefore, it was examined whether stimulation of Swiss 3T3 cells with
      insulin causes changes in the subcellular distribution of EGF receptors and
      phospholipase Cgamma1 that could potentially explain the observed synergy or
      costimulation. It was found that insulin effectively induced the accumulation of
      EGF receptors on the actin arc of cells without activation of the EGF receptor.
      In contrast, EGF, when added for several hours, did not cause accumulation of the
      EGF receptor at this site. However, both EGF and insulin stimulated the
      accumulation of phospholipase Cgamma1 at the actin arc, which was coincident with
      the EGF receptor in the case of insulin- stimulated cells. Therefore, it is
      suggested that the insulin-induced coclustering of the EGF receptor with
      phospholipase Cgamma1 at the actin arc may allow for greater efficiency of signal
      transduction, resulting in the synergy observed for these two hormones in
      stimulation of DNA synthesis.

PMID- 10947868
TI  - The flightless I protein localizes to actin-based structures during embryonic
      development.
AB  - The product of the flightless I gene is predicted to provide a link between
      molecules of an as yet unidentified signal transduction pathway and the actin
      cytoskeleton. Previous work has shown that weak and severe mutations of the
      flightless I locus in Drosophila melanogaster cause disruption in the indirect
      flight muscles and in embryonic cellularization events, respectively, indicative
      of a regulatory role for the flightless I protein in cytoskeletal rearrangements.
      A C-terminal domain within flightless I with significant homology to the gelsolin
      like family of actin-binding proteins has been identified, but evidence of a
      direct interaction between endogenous flightless I and actin remains to be shown.
      In the present study, chick, mouse and Drosophila melanogaster embryos have been
      examined and the localization of flightless I investigated in relation to the
      actin cytoskeleton. It is shown that flightless I localization is coincident with
      actin-rich regions in parasympathetic neurons harvested from chicks, in mouse
      blastocysts and in structures associated with cellularization in Drosophila
      melanogaster.

PMID- 10947869
TI  - Signalling organelle for retrograde axonal transport of internalized
      neurotrophins from the nerve terminal.
AB  - The retrograde axonal transport of neurotrophins occurs after receptor-mediated
      endocytosis into vesicles at the nerve terminal. We have been investigating the
      process of targeting these vesicles for retrograde transport, by examining the
      transport of [125I]-labelled neurotrophins from the eye to sympathetic and
      sensory ganglia. With the aid of confocal microscopy, we examined the phenomena
      further in cultures of dissociated sympathetic ganglia to which rhodamine
      labelled nerve growth factor (NGF) was added. We found the label in large
      vesicles in the growth cone and axons. Light microscopic examination of the
      sympathetic nerve trunk in vivo also showed the retrogradely transported material
      to be sporadically located in large structures in the axons. Ultrastructural
      examination of the sympathetic nerve trunk after the transport of NGF bound to
      gold particles showed the label to be concentrated in relatively few large
      organelles that consisted of accumulations of multivesicular bodies. These
      results suggest that in vivo NGF is transported in specialized organelles that
      require assembly in the nerve terminal.

PMID- 10947870
TI  - Peroxisome proliferator-activated receptors in tumorigenesis: targets of tumour
      promotion and treatment.
AB  - The peroxisome proliferator-activated receptors (PPAR) are ligand-activated
      transcription factors. There are three genes that code for the PPAR isoforms:
      PPARalpha, PPARbeta and PPARgamma. In the present review, studies characterizing
      the various PPAR isoforms are discussed. Peroxisome proliferator-activated
      receptor alpha has been implicated in the lipid-lowering effects of the fibrate
      drugs. Peroxisome proliferator-activated receptor gamma has a clear role in
      adipocyte differentiation and is therapeutically targeted by the
      thiazolidinedione drugs for the treatment of type II diabetes. The physiological
      role of PPARbeta is less well understood but, as described in the present review,
      recent studies have implicated it with a role in colon cancer. In the present
      review, particular attention is focused on the role of PPAR in the regulation of
      expression of proteins associated with cell cycle control and tumorigenesis.

PMID- 10947871
TI  - Neurotransmitter release at ribbon synapses in the retina.
AB  - The synapses of photoreceptors and bipolar cells in the retina are easily
      identified ultrastructurally by the presence of synaptic ribbons, electron-dense
      bars perpendicular to the plasma membrane at the active zones, extending about
      0.5 microm into the cytoplasm. The neurotransmitter, glutamate, is released
      continuously (tonically) from these 'ribbon synapses' and the rate of release is
      modulated in response to graded changes in the membrane potential. This contrasts
      with action potential-driven bursts of release at conventional synapses. Similar
      to other synapses, neurotransmitter is released at ribbon synapses by the calcium
      dependent exocytosis of synaptic vesicles. Most components of the molecular
      machinery governing transmitter release are conserved between ribbon and
      conventional synapses, but a few differences have been identified that may be
      important determinants of tonic transmitter release. For example, the presynaptic
      calcium channels of bipolar cells and photoreceptors are different from those
      elsewhere in the brain. Differences have also been found in the proteins involved
      in synaptic vesicle recruitment to the active zone and in synaptic vesicle
      fusion. These differences and others are discussed in terms of their implications
      for neurotransmitter release from photoreceptors and bipolar cells in the retina.

PMID- 10947872
TI  - Cellular function of p70S6K: a role in regulating cell motility.
AB  - The 70 kDa ribosomal S6 kinase (p70S6K) is activated by numerous mitogens, growth
      factors and hormones. Activation of p70S6K occurs through phosphorylation at a
      number of sites and the primary target of the activated kinase is the 40S
      ribosomal protein S6, a major component of the machinery involved in protein
      synthesis in mammalian cells. In addition to its involvement in regulating
      translation, p70S6K activation has been implicated in cell cycle control and
      neuronal cell differentiation. Recent data obtained in this laboratory suggests
      that p70S6K may also function in regulating cell motility, a cellular response
      that is important in tumour metastases, the immune response and tissue repair.
      The present paper reviews the regulation and cellular function of p70S6K and
      proposes a novel function of p70S6K in regulating cell motility.

PMID- 10947873
TI  - Targeted intracellular delivery of photosensitizers to enhance photodynamic
      efficiency.
AB  - Photodynamic therapy (PDT) is a novel treatment, used mainly for anticancer
      therapy, that depends on the retention of photosensitizers (PS) in tumour cells
      and irradiation of the tumour with appropriate wavelength light. Photosensitizers
      are molecules such as porphyrins and chlorins that, on photoactivation, effect
      strongly localized oxidative damage within target cells. The PS used for PDT
      localize in various cytoplasmic membranous structures, but are not found in the
      most vulnerable intracellular sites for reactive oxygen species, such as the cell
      nucleus. The experimental approaches discussed in the present paper indicate that
      it is possible to design highly efficient molecular constructs, PS carriers, with
      specific modules conferring cell-specific targeting, internalization, escape from
      intracellular vesicles and targeting to the most vulnerable intracellular
      compartments, such as the nucleus. Nuclear targeting of these PS-carrying
      constructs results in enhanced photodynamic activity, maximally about 2500-fold
      that of free PS. Future work is intended to optimize this approach to the point
      at which tumour cells can be killed rapidly and efficiently, while minimizing
      normal cell and tissue damage.

PMID- 10947874
TI  - Medical ethics in the 21st century.
AB  - OBJECTIVES: To foresee how medical ethics may develop in the 21st century.
      DESIGN: We have looked into our crystal ball to see what factors are likely to
      drive medical ethics over the next few decades. We have given examples of how
      such factors might affect specific issues. RESULTS: Those factors that we
      identified as likely to shape the future of medical ethics are: Globalization:
      Medical ethics is likely to have to grapple increasingly with ethical issues
      arising from the huge discrepancies in the level of health care available in
      different countries. Increase in longevity: We predict that there will be, at
      least amongst the richer nations, a significant increase in life expectancy. This
      will result in issues of resource allocation becoming increasingly problematic
      within medicine. Child enhancement: Developments in genetics combined with
      control of reproduction will make it possible to select our children for a broad
      range of characteristics. There are optimistic and pessimistic predictions as to
      how such power will be used. In either case, this area will be an important focus
      of concern in medical ethics. The biological determination of behaviour: Genetic
      research will lead to an increasing sense that undesirable behaviour is
      genetically determined. This will lead to a re-examination of such concepts as
      criminal responsibility. Therapeutic research and clinical practice: We predict
      that an increasing amount of clinical practice will be within the setting of
      clinical trials. The ethics of therapeutic research and clinical practice will
      need to be brought within a coherent framework.

PMID- 10947875
TI  - Prevalence of carotid artery kinking in 590 consecutive subjects evaluated by
      Echocolordoppler. Is there a correlation with arterial hypertension?
AB  - OBJECTIVE: To assess a possible correlation between high blood pressure and
      prevalence of kinking in carotid arteries. DESIGN: Between July 1, 1997 and
      December 31, 1998, we evaluated the subjects submitted to Echocolordoppler
      examination of carotid arteries. SETTING: Patients were examined at the
      Laboratory for Noninvasive Vascular Diagnostics of the University Hospital in
      Verona. SUBJECTS: 590 consecutive subjects (M/F ratio, 1/1.2; mean age, 67 years;
      range, 36-86 years). MAIN OUTCOME MEASURES: An Echocolordoppler ultrasonograph to
      evaluate by means of the standard longitudinal and transverse scans the usual
      parameters of both intima-to-lumen interface and flow. Moreover, particular
      attention was paid to the analysis of the conformational characteristic of the
      vessels. Kinking has been classified in three classes according to the degree of
      bending. All the subjects were asked to compile a questionnaire that provided us
      with the clinical history. RESULTS: The prevalence of hypertension in the
      subjects with kinking appeared higher than in subjects without this abnormality
      (chi2 = 6.44, P < 0. 02). We found also a significant association between kinking
      and transitory ischaemic attacks (chi2 = 6.987, P < 0.01). CONCLUSIONS: The high
      prevalence of kinking in the hypertensives agrees with the pathogenetical
      hypothesis ascribing a role to the high endoluminal pressure. The presence of
      hypertension and kinking of the internal carotid artery suggests that they could
      be additive risk factors in the pathophysiology of a transitory ischaemic attack.

PMID- 10947876
TI  - The role of habitual snoring and obesity in the development of diabetes: a 10
      year follow-up study in a male population.
AB  - OBJECTIVES: There are many similarities between diabetes (mainly type 2) and
      sleep breathing disturbances regarding risk factors, anthropometric criteria and
      consequences of morbidity and mortality. The aim of this study was to investigate
      whether the association between habitual snoring and diabetes is entirely
      dependent on obesity. DESIGN: A population-based prospective study. SETTING: The
      municipality of Uppsala, Sweden. SUBJECTS AND METHODS: In 1984 and in 1994, 2668
      men aged 30-69 years at baseline answered questionnaires concerning sleep
      breathing disturbances and somatic diseases. RESULTS: Of those with habitual
      snoring in 1984, 5.4% reported that they had developed diabetes during the 10
      year period compared with 2.4% of those without habitual snoring (P < 0.001).
      Amongst obese snorers, 13.5% developed diabetes compared with 8.6% of obese non
      snorers (P = 0.17). In a multiple logistic regression model, the odds ratio (95%
      confidence interval) for development of diabetes was higher in obese snorers [7.0
      (2.9-16.9)] than in obese non-snorers [5.1 (2.7-9.5)] after adjustment for age,
      weight gain, smoking, alcohol dependence and physical inactivity. CONCLUSIONS: We
      conclude that, in males aged 30-69 years, habitual snoring is associated with an
      increased incidence of diabetes within 10 years. Although obesity is the main
      risk factor for developing diabetes, coexistent habitual snoring may add to this
      hazard.

PMID- 10947877
TI  - Does dialysis therapy improve autonomic and peripheral nervous system
      abnormalities in chronic uraemia?
AB  - OBJECTIVES: Autonomic nervous system (ANS) dysfunction and peripheral neuropathy
      occur in patients with chronic renal insufficiency. Adequate renal replacement
      therapy should prevent development or correct these abnormalities. DESIGN AND
      SUBJECTS: We studied retrospectively ANS and peripheral neuropathy in 32 patients
      with chronic uraemia who received either haemodialysis (16) or peritoneal
      dialysis (16) therapy, and compared the observed dialysis efficiency with changes
      in neurological function. METHODS: Heart rate variability (HRV) time domain
      indices and peripheral sensory nerve conduction studies were followed for a mean
      of 2.9 years. The adequacy of haemodialysis (HD) efficiency was estimated by
      Kt/V, an index of fractional urea clearance. Adequacy of continuous ambulatory
      peritoneal dialysis (CAPD) was estimated on the basis of the patient's wellbeing
      and nutritional status as excellent, satisfactory or poor. Based on observed
      changes in HRV time domain measures, the observations were divided in three
      subgroups: improved, unchanged or deteriorated. RESULTS: The peripheral sensory
      nerve conduction studies were abnormal in 38% of the patients and did not change
      significantly during the study. Improvement in HRV time domain measures occurred
      in HD patients with mean Kt/V > 1.20 or in CAPD patients with satisfactory or
      excellent response to dialysis treatment. Values of Kt/V < 0.85 in HD patients
      were associated with progressive deterioration of autonomic neuropathy. Diabetic
      patients (n = 4) differed from others as their HRV was grossly abnormal and did
      not improve. CONCLUSIONS: The adequacy of haemodialysis is a predictor of
      improvement of cardiac autonomic nervous function in chronic uraemia. The same
      trend of improvement was seen also in CAPD patients.

PMID- 10947878
TI  - Signs of neuropathy in the lower legs and feet of patients with acute
      intermittent porphyria.
AB  - OBJECTIVE: To assess signs of distal neuropathy in patients with acute
      intermittent porphyria (AIP). DESIGN: A population-based study. SUBJECTS: All
      patients with DNA-verified AIP >/= 18 years of age in the four most northerly
      counties of Sweden. INTERVENTION: Validated neuropathic signs and tests such as
      monofilament test, neuropathic pain, dry feet, extensor digitorum brevis (EDB)
      test, loss of forefoot arch, hammer toes and ulceration. RESULTS: A total of 356
      patients were registered and 339 of them (95%) participated in the neuropathy
      study. The chronic neurological signs were symmetrical and similar to those in
      type 1 diabetic patients. Significant impairment was found concerning perception,
      EDB test, lower leg pain, ankle and knee tendon reflexes, but not concerning dry
      feet, loss of forefoot arch and hammer toes, on comparing patients with manifest
      versus latent AIP. The neurological signs were more severe in the diabetic
      patients (n = 298). Five AIP patients had permanent quadriplegia after severe
      attacks. CONCLUSIONS: Patients with manifest AIP had significantly more signs of
      distal chronic, symmetrical neuropathy of axonal type than did patients with
      latent AIP. More grave neurological lesions appear to develop after severe
      attacks.

PMID- 10947879
TI  - Serum level of soluble tumour necrosis factor receptor II (75 kDa) indicates
      inflammatory activity of sarcoidosis.
AB  - OBJECTIVES: Tumour necrosis factor alpha (TNFalpha) is a key cytokine involved in
      granuloma formation of sarcoidosis. Since soluble TNF receptors (sTNF-R) are
      known to inhibit TNF effects, we were interested in whether they are elevated in
      the serum of sarcoidosis patients. METHODS: We determined serum levels of sTNF-R
      I (55 kDa) and sTNF-R II (75 kDa) in 49 patients with sarcoidosis and 22
      controls. The clinical course of the disease was re-evaluated in a follow-up
      after (mean +/- SE) 6.8 +/- 6.6 months. RESULTS: sTNF-R I (3.1 +/- 1.1 ng mL-1, P
      < 0.05) and sTNF-R II (5.5 +/- 2.7 ng mL-1, P < 0.0005) were significantly
      elevated in sarcoidosis compared with controls (2.4 +/- 0.7 and 3.0 +/- 1.3 ng mL
      1, respectively). Interestingly, both sTNF receptors were significantly higher in
      the serum of patients with active compared with inactive sarcoidosis (P < 0.005
      and P < 0.0005, respectively). Furthermore, serum sTNF-R II levels were
      significantly higher in sarcoidosis patients with advanced radiological types II
      and III. In 10 patients, serum sTNF-R levels were obtained before and after
      systemic corticosteroid therapy and we observed a significant decrease of sTNF-R
      II (P < 0.02), whereas sTNF-R I levels were not reduced significantly.
      CONCLUSIONS: Both types of sTNF receptors are elevated in the serum of
      sarcoidosis patients with active disease, but only the sTNF-R II seems to be
      useful for monitoring the inflammatory activity of the disease.

PMID- 10947881
TI  - A comparison between patients suffering in-hospital and out-of-hospital cardiac
      arrest in terms of treatment and outcome.
AB  - AIM: To compare treatment and outcome amongst patients suffering in-hospital and
      out-of-hospital cardiac arrest in the same community. PATIENTS: All patients
      suffering in-hospital cardiac arrest in Sahlgrenska University Hospital covering
      half the catchment area of the community of Goteborg (500 000 inhabitants) and
      all patients suffering out-of-hospital cardiac arrest in the community of
      Goteborg. Criteria for inclusion were that resuscitation efforts should have been
      attempted. TIME OF SURVEY: From 1 November 1994 to 1 November 1997. METHODS: Data
      were recorded both prospectively and retrospectively. RESULTS: In total, 422
      patients suffered in-hospital cardiac arrest and 778 patients suffered out-of
      hospital cardiac arrest. Patients with in-hospital cardiac arrest included more
      women and were more frequently found in ventricular fibrillation. The median
      interval between collapse and defibrillation was 2 min in in-hospital cardiac
      arrest compared with 7 min in out-of-hospital cardiac arrest (< 0.001). The
      proportion of patients being discharged from hospital was 37.5% after in-hospital
      cardiac arrest, compared with 8.7% after out-of-hospital cardiac arrest (P <
      0.001). Corresponding figures for patients found in ventricular fibrillation were
      56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P <
      0.001). CONCLUSION: In a survey evaluating patients with in-hospital and out-of
      hospital cardiac arrest in whom resuscitation efforts were attempted, we found
      that the former group had a survival rate more than four times higher than the
      latter. Possible strong contributing factors to this observation are: (i) shorter
      time interval to start of treatment, and (ii) a prepared selection for
      resuscitation efforts.

PMID- 10947880
TI  - LDL particle size in relation to intima-media thickness and plaque occurrence in
      the carotid and femoral arteries in patients with hypercholesterolaemia.
AB  - OBJECTIVES: Small LDL particle size has been shown to be associated with coronary
      artery disease. However, no previous study has been performed relating LDL
      particle size to ultrasound measurement of atherosclerosis in
      hypercholesterolaemic subjects. The main aims of the present study were
      therefore: (i) to investigate the relationship between intima-media thickness
      (IMT) of the carotid bulb and LDL particle size in patients with primary
      hypercholesterolaemia (n = 102) and in matched normocholesterolaemic controls (n
      = 102); and (ii) to investigate the relationship between plaque occurrence in the
      carotid and femoral arteries and LDL particle size. LDL particle size was
      determined by subjecting serum to 2-16% polyacrylamide gradient gel
      electrophoresis. RESULTS: The results showed that patients with primary
      hypercholesterolaemia had smaller LDL peak particle size compared with healthy
      control subjects (P < 0.001 for men, P = 0.006 for women). However, the
      difference in LDL peak particle size between patients with hypercholesterolaemia
      and controls disappeared when adjusting for serum triglycerides. There was no
      association between increasing IMT of the carotid bulb and decreasing LDL peak
      particle size or between the occurrence of moderate to large plaques in the
      carotid and femoral arteries and small LDL peak particle size. However, metabolic
      variables such as serum triglycerides, HDL, blood glucose, body mass index, and
      also systolic blood pressure were associated with LDL peak particle size.
      CONCLUSION: The lack of an association between atherosclerosis, as measured by
      ultrasound, and small LDL particle size in patients with hypercholesterolaemia
      implies that other risk factors, such as hypercholesterolaemia and high blood
      pressure, may overshadow any importance of small LDL particle size.

PMID- 10947882
TI  - IL-6 and IL-1 receptor antagonist in stable angina pectoris and relation of IL-6
      to clinical findings in acute myocardial infarction.
AB  - OBJECTIVES: To determine if increased inflammatory activity, as reflected by
      interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) levels, is
      present in patients with stable angina pectoris and if IL-6 levels on admission
      to the coronary care unit in patients with acute myocardial infarction (AMI) are
      related to heart failure and fever response. SUBJECTS AND METHODS: We studied 28
      patients with stable angina pectoris enrolled for coronary angiography, and
      compared them with sex- and age-matched controls. Thirty-four patients with AMI
      were studied and samples for determination of IL-6 levels were taken on admission
      within 36 h of onset of symptoms. IL-6 and IL-1ra were determined in serum by
      enzyme immunoassay. RESULTS: Levels of IL-6 and IL-1ra were higher in patients
      with stable angina pectoris than in controls (mean 4.6 +/- 3.6 vs. 3.0 +/- 2.9 ng
      L-1, P < 0.03, and 774 +/- 509 vs. 490 +/- 511 ng L-1, P < 0.01, respectively).
      IL-6 and IL-1ra levels were not related to angiographic findings. IL-6 levels
      were high in patients with AMI (38.9 +/- 75.6 ng L-1). Patients with prolonged
      fever (duration > 4 days) had higher IL-6 levels (94.7 +/- 138.2 vs. 21.7 +/-
      29.7 ng L-1, P < 0.05). IL-6 levels were not related to heart failure.
      CONCLUSIONS: Our results indicate that increased inflammatory activity is present
      not only in acute coronary syndromes, but also in a chronic form of ischaemic
      heart disease, giving further evidence for a central role of inflammatory
      processes in coronary artery disease. With regard to AMI, we found increased
      inflammatory activity in patients with prolonged fever.

PMID- 10947883
TI  - Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes
      mellitus and its association with glycaemic control and cardiovascular risk
      factors.
AB  - OBJECTIVES: Diabetic patients reveal a significant increase in their
      cardiovascular risk. Beside glycaemic control and management of established risk
      factors, determination of cytokines, like serum levels of tumour necrosis factor
      alpha (TNF-alpha), might offer a tool to determine patients at high risk. The
      cytokine TNF-alpha reveals a complex relationship with diabetes. It is involved
      in beta-cell damage leading to type 1 diabetes, causes insulin resistance
      associated with obesity and is of influence in the formation of atherosclerotic
      vascular lesions. We were interested in the possible association of this cytokine
      with metabolic control and cardiovascular risk factors in patients with type 1
      diabetes. DESIGN AND SUBJECTS: TNF-alpha plasma levels were determined in 44
      outdoor patients (15 women, 29 men) with type 1 diabetes mellitus (mean duration
      11.2 +/- 8.7 years) and in 24 healthy controls by use of a solid phase enzyme
      amplified sensitivity immunoassay (TNF-alpha ELISA, Biosource Fleurus, Belgium).
      None of our study participants suffered from inflammatory or other concurrent
      diseases. Relationships between variables were evaluated by non-parametric
      Spearman correlation coefficients. RESULTS: TNF-alpha plasma levels were
      significantly higher in diabetic patients (19.3 +/- 7.5 pg mL-1) than in non
      diabetic subjects (11.1 +/- 5.8 pg mL-1; P < 0. 023), and revealed a significant
      positive correlation with glycated haemoglobin (HbA1c) (r = 0.43; P < 0.004) and
      fructosamine (r = 0. 31; P < 0.049) values, and a negative correlation with HDL
      cholesterol (r = -0.36; P < 0.018) and apoAI-levels (r = -0.37; P < 0.015). These
      relationships could be observed in patients with a duration of diabetes for more
      than 5 years, as well as in patients with a shorter duration of diabetes. In the
      male group, TNF-alpha plasma levels revealed a significant positive correlation
      with plasma levels of thiobarbituric acid reacting substances (r = 0.61; P <
      0.001). Plasma levels of thiobarbituric acid reacting substances showed a
      positive correlation with the duration of diabetes (r = 0. 58; P < 0.008), as
      well as with the serum levels of the vascular adhesion molecules intercellular
      adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascular cell adhesion
      molecule (VCAM) (r = 0.30; P < 0.052). CONCLUSIONS: Our data indicate that TNF
      alpha plasma levels are increased in type 1 diabetes mellitus and reveal a
      significant association with metabolic long-term control parameters, HbA1c and
      fructosamine for glycaemic control, and HDL cholesterol for triglyceride
      metabolism, as well with lipid peroxidation.

PMID- 10947884
TI  - The common pentanucleotide polymorphism of the 3'-untranslated region of the
      leptin receptor gene is associated with serum insulin levels and the risk of type
      2 diabetes in non-diabetic men: a prospective case-control study.
AB  - OBJECTIVES: The purpose of the study was to test whether the pentanucleotide
      insertion/deletion polymorphism in the 3'-untranslated region (3'-UTR) of the
      leptin receptor gene, which has previously been associated with serum insulin
      levels in obese subjects, is associated with insulin levels and the risk of type
      2 diabetes in non-diabetic middle-aged men. SUBJECTS AND DESIGN: We studied these
      associations in a prospective population-based nested case-control study in 41
      men who developed type 2 diabetes during 4-year follow-up and 81 controls who
      were matched for age, obesity, baseline glucose and insulin and other strongest
      risk factors. Both the cases and the controls came from a cohort of 985 men who
      had no diabetes at baseline. RESULTS: There was one homozygote and 22
      heterozygotes for the 3'-UTR insertion allele amongst all 122 men. The carrier
      frequency of this allele was 9.8% amongst the cases and 23.5% amongst the
      controls. At baseline, the mean fasting serum insulin was 12.2 mU L-1 in the 23
      men who were heterozygous or homozygous for the insertion allele and 17.1 mU L-1
      in the 99 men who were homozygous for the deletion allele (P = 0.005). In a
      logistic regression model adjusting for four strongest non-matched predictors of
      type 2 diabetes, the carriers of the insertion allele had a 79% reduced risk of
      diabetes (OR = 0.21; 95% CI = 0.06-0.77, P = 0.019), compared with non-carriers.
      CONCLUSION: Our findings support the hypothesis that alterations in the leptin
      signalling system could contribute to serum insulin levels and the development of
      type 2 diabetes.

PMID- 10947885
TI  - Left ventricular calcification following resuscitation.
AB  - In this paper we report a case of 34-year-old man with a severe septic shock.
      Because of profound hypotension he was given massive amounts of catecholamines
      for 10 days. After a short recovery the function of his heart started to
      deteriorate again and clear calcification around the left ventricle was disclosed
      by computer tomography. Catecholamines are known to induce myocardial injury
      resulting in a special form of cardiomyopathy with eventual calcification, but
      there are no previous reports of myocardial calcification to this extent.

PMID- 10947886
TI  - Alstrom's syndrome with Kleinfelter's karyotype.

PMID- 10947887
TI  - Medical education in the new millennium.
AB  - This article reviews current trends in undergraduate and postgraduate medical
      education and speculates on the future in the new millennium.

PMID- 10947888
TI  - Cigarette smoking, oral moist snuff use and glucose intolerance.
AB  - OBJECTIVE: To investigate the association between cigarette smoking and use of
      oral moist snuff and impaired glucose tolerance and type 2 diabetes. DESIGN: We
      performed a population-based cross-sectional study of glucose intolerance and
      tobacco use in Stockholm during 1992-94. The sample consisted of 3128 men, aged
      35-56 years, of whom 52% had a family history of diabetes. In an oral glucose
      tolerance test, we detected 55 men with type 2 diabetes and 172 with impaired
      glucose tolerance. Information on cigarette smoking and oral moist snuff use was
      collected by a questionnaire. RESULTS: The odds ratio of type 2 diabetes was
      increased for smokers of 25+ cigarettes day-1 (odds ratio = 2.6, 95% confidence
      interval = 1.1-5.9) as well as for moist snuff dippers of 3+ boxes week-1 (odds
      ratio = 2.7, 95% confidence interval = 1.3-5.5). The odds ratio of relatively
      high (highest tertile) fasting insulin levels in subjects with impaired glucose
      tolerance associated with cigarette smoking of 25+ cigarettes day-1 was 1.5 (95%
      confidence interval = 0.7-3.6). The corresponding estimate of a relatively low
      (lowest tertile) 2 h insulin response was 2.5 (95% confidence interval = 0.9
      7.1). CONCLUSIONS: These results indicate that heavy users of cigarettes or moist
      snuff have an increased risk of type 2 diabetes. The results could suggest that
      tobacco use is associated with a low insulin response.

PMID- 10947889
TI  - Cardiovascular risk factors and testing of relatives amongst patients with
      familial hyperlipidaemia one decade after a clinical trial.
AB  - OBJECTIVES: We examined the cardiovascular disease risk factor status of men and
      women with familial hyperlipidaemia (FH) 10-11 years after a clinical trial and
      asked whether first-degree relatives had undergone lipid testing. DESIGN SETTING
      AND SUBJECTS: Subjects started lipid-lowering drugs in 1987-88. Of 60 subjects,
      12 had died, one emigrated and 35 men and 12 women took part in a follow-up
      clinical examination in 1998. RESULTS: Total cholesterol level was reduced by 41%
      and high-density lipoprotein (HDL) cholesterol level increased by 13% compared
      with baseline (diet alone). Low-density lipoprotein (LDL) cholesterol level was
      lower at the end of the trial than at follow-up (3.6 +/- 1.5 vs. 4.6 +/- 2.2 mmol
      L-1; P = 0.01) and was higher in the group taking a low dose of a statin alone
      compared with other drug groups. Thus, two-thirds of the subjects required
      adjustment of lipid-lowering drugs to reach target lipid levels. One-fifth
      consumed at least two food groups rich in saturated fat regularly. Body mass
      index (BMI) increased from 25.6 +/- 2.9 to 26.8 +/- 3.3 kg m-2 (P < 0.001). Five
      subjects compared with one at baseline had type II diabetes or glucose
      intolerance; 12 compared with four at baseline had a blood pressure of >/= 160
      mmHg systolic or >/= 95 mmHg diastolic. Plasma total homocysteine was higher in
      subjects with coronary artery disease than in subjects without disease (11.7 +/-
      3.9 vs. 9.0 +/- 2.3 micromol L-1; P = 0.01). Barriers to testing for lipids
      amongst children or siblings included family feuds, fear of increased insurance
      and psychiatric disease. CONCLUSION: The majority of subjects were undertreated.
      Increases in BMI, blood pressure and glucose levels and the diet posed challenges
      to risk reduction. Plasma homocysteine levels should be considered in this group.
      Testing of all first-degree relatives may not be achievable because of
      psychological barriers.

PMID- 10947890
TI  - Diabetes mellitus is a strong negative prognostic factor in patients with
      myocardial infarction treated with thrombolytic therapy.
AB  - OBJECTIVES: To assess the long-term prognostic values of baseline demographic
      data, occurrence of vectorcardiographic signs of reperfusion, left ventricular
      function and coronary angiographic features. DESIGN: Longitudinal study of
      morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital,
      Stockholm, Sweden. SUBJECTS: A total of 222 patients (mean age 61 years) with a
      suspected acute myocardial infarction treated with thrombolysis were investigated
      and followed for 2-5 years (mean 1216 days). MAIN OUTCOME MEASURES: Death or a
      new myocardial infarction. RESULTS: Age above 55 years (P < 0.05), a previous
      diagnosis of diabetes mellitus (P < 0.005), hypertension (P < 0.05), heart
      failure (P < 0.001) and myocardial infarction (P < 0.05), a previous use of beta
      blockers (P < 0.05) and an ejection fraction below 60% (P < 0.01) were predictors
      for death or a new myocardial infarction in univariate analysis. Sex, a previous
      history of smoking or angina pectoris, vectorcardiographic signs of reperfusion
      or degree of coronary artery disease had no prognostic values. In multivariate
      analysis including age above 55 years, a previous diagnosis of diabetes mellitus,
      hypertension and myocardial infarction, and an ejection fraction below 60%, only
      age (P < 0.05), diabetes mellitus (P < 0. 01) and ejection fraction (P < 0.05)
      were predictors for death or a new myocardial infarction. CONCLUSIONS: The
      results of the present study emphasize the importance of diabetes mellitus as a
      long-term prognostic risk factor in patients with myocardial infarction treated
      with thrombolysis. Further studies are needed to determine the mechanisms behind
      this increased risk.

PMID- 10947891
TI  - Changes in ventricular repolarization during percutaneous transluminal coronary
      angioplasty in humans assessed by QT interval, QT dispersion and T vector loop
      morphology.
AB  - OBJECTIVES: Based on clinical, epidemiological, and experimental data, transient
      cardiac ischaemia is one of the major triggering factors of malignant ventricular
      arrhythmia. According to animal studies, increased dispersion of repolarization
      is of pathophysiological relevance in this context. Therefore we explored the
      impact of myocardial ischaemia during single vessel coronary angioplasty on the
      change in ventricular repolarization, measured by QT and JT intervals and their
      dispersion in the 12-lead electrocardiogram. We also assessed a novel method, the
      3-dimensional T vector loop, to find out whether it was sensitive to changes in
      ventricular repolarization during ischaemia, and whether there was any
      correlation with changes in the dispersion of the QT and/or JT intervals. DESIGN:
      This study was prospective with consecutive patients. Only patients in sinus
      rhythm and without bundle branch block were included. SETTING: All coronary
      angioplasties were performed at Norrlands University Hospital, Umea. The analysis
      of the material was performed at the Karolinska Hospital, Stockholm. SUBJECTS:
      Twenty-nine consecutive patients went through 30 elective one-vessel percutaneous
      transluminal coronary angioplasty (PTCA) procedures. PTCA was performed in 10
      stenoses of the left anterior descending, 10 of the left circumflex, and 10 of
      the right coronary artery. INTERVENTIONS: A 12-lead electrocardiogram was
      recorded continuously as part of routine monitoring of the patient during PTCA
      and the T vector loop was calculated from the simultaneously recorded. X, Y, Z
      leads. MAIN OUTCOME MEASURES: Repolarization was assessed by the QRS, QT and JT
      intervals as well as by the T vector loop parameters (Tarea, Tavplan, and
      Teigenv) before and at the end of the first occlusion during PTCA. RESULTS: PTCA,
      with an average occlusion time of 171 +/- 60 s (mean +/- SD), induced ischaemia
      on the 12-lead electrocardiogram in 73% of cases. The overall response for the 30
      procedures was a significantly increased dispersion of ventricular
      repolarization, both corrected and uncorrected for heart rate. QT dispersion
      increased by, on average, 19% from 74 +/- 35 to 88 +/- 36 ms, QTc dispersion by
      27% from 71 +/- 39 to 90 +/- 42 ms, and JTc dispersion by 19% from 78 +/- 32 to
      94 +/- 43 ms (P < 0.05). The T vector loop became more circular and bulgy during
      occlusion (all three parameters changed by between 33% and 59%). There was a
      significant correlation between changes in one of the T vector loop parameters
      (Teigenv), and changes in JT and QT dispersion in the left anterior descending
      group. CONCLUSIONS: Transient ischaemia during PTCA induced significant changes
      in ventricular repolarization, especially during occlusion of the left anterior
      descending artery and resulted in a significant increase in both QT and QTc
      dispersion. The degree of QT dispersion was such that several patients were at
      risk of ventricular arrhythmia, if a proper triggering extrasystole had occurred.
      In addition, and as an original observation, the 3-dimensional T vector loop
      morphology seemed even more sensitive to coronary occlusion than QT dispersion.

PMID- 10947892
TI  - Lung function study and diffusion capacity in anorexia nervosa.
AB  - STUDY OBJECTIVES: In humans, malnutrition alters the respiratory system in
      different ways. It impairs the ventilatory drive, decreases respiratory muscle
      strength and reduces immune competence. In addition, typical emphysema-like
      changes were demonstrated in starved animals. The presence of emphysema has never
      been demonstrated in starved humans. Our objective was to investigate whether
      pulmonary emphysema occurs in anorexia nervosa by means of a pulmonary function
      study. POPULATION AND METHOD: We examined 24 women aged between 14 and 38 years
      (nine smokers). We studied the lung function including lung volumes, ventilatory
      capacity, maximal respiratory pressures and transfer factor, as well as PaO2.
      RESULTS: All respiratory tests were within normal limits with the exception of
      decreased maximal inspiratory (59% of predicted values) and expiratory pressures
      (35%), and increased residual volume (162%). Diffusion capacity (98.1 +/- 16.2%)
      and transfer coefficient (98.4 +/- 16.2%) were also normal. The diffusion
      coefficient was lower in current smokers than in those who had never smoked (P <
      0.01), a difference similar to that calculated from existing reference values for
      transfer factor for smokers and nonsmokers. CONCLUSION: In anorexia nervosa,
      pulmonary function tests are within normal limits with the exception of maximal
      pressures and residual volume. Diffusion capacity is not decreased. The present
      results within the limitations of the used method are not compatible with the
      hypothesis of starvation-induced pulmonary emphysema.

PMID- 10947893
TI  - Postmenopausal hormone therapy: less favourable risk-benefit ratios in healthy
      Dutch women.
AB  - OBJECTIVES: To estimate the health effects of postmenopausal hormone therapy used
      for 10 or 20 years in a population of intermediate cardiovascular risk. DESIGN:
      Using existing estimates of the effect of hormone therapy on rates of myocardial
      infarction, hip fracture and breast cancer, a proportional multistage life table
      was generated to calculate the effects of use for 10 and 20 years in a synthetic
      cohort of Dutch women aged 55 with an average and a high-risk profile for
      cardiovascular disease. RESULTS: A woman of the general population who starts
      hormone therapy at age 55 for 10 years can prolong her life by 1 month and may
      postpone the occurrence of first incidence of one of the diseases under
      consideration by 2.4 months. One excess breast cancer case is likely to occur per
      5-6 averted cases of first myocardial infarction or hip fracture. If she prolongs
      her use to 20 years, the gain of life expectancy and disease-free life expectancy
      is doubled. The risk-benefit ratio worsens to one extra breast cancer per 3-4
      averted cases of the preventable diseases. For a woman with a high-risk profile,
      the gains in health are about twice as high as for her counterpart in the general
      population, and her risk-benefit ratio is also more favourable. Yet, the risk
      benefit ratio still worsens for 20 as compared with 10 years of use. CONCLUSIONS:
      Women from the general population in the Netherlands and similar populations can
      achieve only a modest gain in life expectancy by using hormones during 10 or 20
      years following menopause. This is a consequence of the low incidence of
      myocardial infarction and hip fracture and the relatively high incidence of
      breast cancer before the age of 75. Women at increased cardiovascular risk can
      benefit more from hormone therapy. But even amongst these women, the risk of
      breast cancer incurred with long-term use offsets much of the benefit that could
      accrue from changing the risk of heart disease and hip fracture.

PMID- 10947894
TI  - Markers of hypercoagulation and von Willebrand factor in postmenopausal women
      with unstable coronary artery disease. Discriminatory ability regarding unstable
      coronary artery disease and coronary atherosclerosis using receiver operating
      characteristics.
AB  - OBJECTIVES: Many women with typical anginal chest pain have normal coronary
      angiograms. The pathogenetic mechanisms behind the chest pain in these patients
      are unknown but may be due to increased thrombogenicity. We evaluated markers of
      hypercoagulation and thrombosis in women with clinical signs of unstable coronary
      artery disease (CAD). METHODS AND RESULTS: A total of 158 patients with unstable
      CAD and 101 controls were examined: 16% of the patients had normal vessels and
      84% had coronary atherosclerosis at coronary angiography. Mean plasma
      concentrations of von Willebrand factor antigen, soluble fibrin (SF), thrombin
      antithrombin complex and D-dimer were significantly higher, whereas there was no
      difference regarding prothrombin fragment 1+2 between patients and controls.
      Patients with coronary atherosclerosis had higher mean plasma levels for most
      variables compared with those with normal coronary vessels, although only
      significantly higher for SF. D-Dimer was significantly higher in patients with
      normal coronary vessels compared with the control group. Although multivariate
      analyses showed strong significant correlations of the haemostatic variables to
      the diagnosis of unstable CAD, receiver operating characteristics (ROC) revealed
      that none of the variables represented high diagnostic accuracy in separating
      patients with unstable CAD. Likewise, none of the variables was particularly good
      at identifying coronary atherosclerosis. CONCLUSION: Our results are in favour of
      a hypercoagulable state in postmenopausal women with unstable CAD and coronary
      atherosclerosis, whereas this does not seem to be the case in patients with
      normal vessels. ROC revealed no variable to be particularly clinically useful in
      separating patients from controls or patients from those without coronary
      atherosclerosis.

PMID- 10947895
TI  - Attack rate, mortality and case fatality for acute myocardial infarction in
      Sweden during 1987-95. Results from the national AMI register in Sweden.
AB  - OBJECTIVE: To assess trends in attack rate, mortality and case-fatality of acute
      myocardial infarction (AMI) in Sweden. SETTING: All 303 324 Swedes discharged
      from hospitals, or deceased, with a diagnosis of AMI between 1987 and 1995.
      DESIGN: Analysis based on the National AMI Register in Sweden. The National AMI
      Register was assembled by linking the records of the National Hospital Discharge
      Register and the National Cause of Death Register in Sweden. MAIN OUTCOME
      MEASURES: Age-standardized attack rate, mortality and case fatality rates for
      AMI. RESULTS: Between 1987 and 1995, the age-standardized attack rate of AMI
      declined by 11% for men and 10% for women, whilst mortality from AMI decreased by
      14% for both sexes. The decrease was most pronounced for men below the age of 64,
      with a reduction of 22% in attack rate and nearly 30% in mortality. There was no
      change over time in the case fatality rates on the date of attack, including also
      deaths outside hospital, whilst case fatality within 28 days decreased from 49 to
      45% amongst men, and 45 to 42% amongst women. This reduction persisted over 1
      year of follow-up. CONCLUSIONS: The decrease in attack rate of AMI in Sweden may
      be attributed both to changes in risk factors amongst the population and to
      improved medical intervention. The decline in case fatality rates indicates that
      improved treatment of patients with AMI has contributed to the reduction in
      mortality. However, the high, and essentially unchanged, proportion of deaths
      outside hospital stresses the importance of disease prevention.

PMID- 10947896
TI  - Treatment of irritable bowel syndrome with loperamide oxide. An open study to
      determine optimal dosage.

PMID- 10947897
TI  - Paradoxical glucose infusion for hypernatraemia in diabetic hyperglycaemic
      hyperosmolar syndrome.

PMID- 10947898
TI  - Reply

PMID- 10947900
TI  - Stereo pair displays of surface range images

PMID- 10947899
TI  - Nimesulide, clavulanic acid and hepatitis.

PMID- 10947901
TI  - An integrated environmental perfusion chamber and heating system for long-term,
      high resolution imaging of living cells.
AB  - This communication presents the design and application of an integrated
      environmental perfusion chamber and stage heating blanket suitable for time-lapse
      video microscopy of living cells. The system consists of two independently
      regulated components: a perfusion chamber suitable for the maintenance of cell
      viability and the variable delivery of environmental factors, and a separate
      heating blanket to control the temperature of the microscope stage and limit
      thermal conduction from the perfusion chamber. Two contrasting experiments are
      presented to demonstrate the versatility of the system. One long-term sequence
      illustrates the behaviour of cells exposed to ceramic fibres. The other shows the
      shrinking response of cultured articular cartilage chondrons under dynamic hyper
      osmotic conditions designed to simulate joint loading. The chamber is simple in
      design, economical to produce and permits long-term examination of dynamic
      cellular behaviour while satisfying the fundamental requirements for the
      maintenance of environmental factors that influence cell viability.

PMID- 10947902
TI  - Three-dimensional spectral precision distance microscopy of chromatin
      nanostructures after triple-colour DNA labelling: a study of the BCR region on
      chromosome 22 and the Philadelphia chromosome.
AB  - Topological analysis of the three-dimensional (3D) chromatin nanostructure and
      its function in intact cell nuclei implies the use of high resolution far field
      light microscopy, e.g. confocal laser scanning microscopy (CLSM). However,
      experimental evidence indicates that, in practice, under biologically relevant
      conditions, the spatial resolution of CLSM is limited to about 300 nm in the
      lateral direction and about 700 nm in the axial direction. To overcome this
      shortcoming, the use of a recently developed light microscopical approach,
      spectral precision distance microscopy (SPDM) is established. This approach is
      based on the precise localization of small labelling sites of a given target in
      spectrally differential images. By means of quantitative image analysis, the bary
      centres (intensity weighted centroid analogous to the centre of mass) of these
      independently registered labelling sites can be used as point markers for
      distance and angle measurements after appropriate calibration of optical
      aberrations (here, polychromatic shifts). In combination with specific labelling
      of very small chromatin target sites with dyes of different spectral signatures
      by fluorescence in situ hybridization (FISH), SPDM presently allows us to analyse
      the nuclear topology in three-dimensionally conserved nuclei with a 'resolution
      equivalent', many times smaller than the conventional optical resolution. Chronic
      myelogeneous leukaemia (CML) is genetically characterized by the fusion of parts
      of the BCR and ABL genes on chromosomes 22 and 9, respectively. In most cases,
      the fusion leads to a translocation t(9; 22) producing the Philadelphia
      chromosome. SPDM was applied to analyse the 3D chromatin structure of the BCR
      region on the intact chromosome 22 and the BCR-ABL fusion gene on the
      Philadelphia chromosome (Ph) by using a new triple-colour FISH protocol: two
      different DNA probes were used to detect the BCR region and the third DNA probe
      was used to identify the location of the ABL gene. Consistent 3D distance
      measurements down to values considerably smaller than 100 nm were performed. The
      angle distributions between the three labelled sites on the Philadelphia
      chromosome territory were compared to two state-of-the-art computer models of
      nuclear chromatin structure. Significant differences between measured and
      simulated angle distributions were obtained, indicating a complex and non-random
      angle distribution.

PMID- 10947903
TI  - Confocal pH imaging of microscopic specimens using fluorescence lifetimes and
      phase fluorometry: influence of parameter choice on system performance.
AB  - We investigate the performance of confocal pH imaging when using phase
      fluorometry and fluorophores with pH-dependent lifetimes. In these experiments,
      the specimen is illuminated by a laser beam, whose intensity is sinusoidally
      modulated. The lifetime-dependent phase shift in the fluorescent signal is
      detected by a lock-in amplifier, and converted into a pH value through a
      calibration procedure. A theoretical investigation is made of how the different
      system parameters will influence the results concerning sensitivity and noise.
      Experiments carried out with the fluorophore SNAFL-2 support these theoretical
      predictions. It is found that, under realistic experimental conditions, we can
      expect a pH change of 0.1 units to be easily detected in an 8-bit digital image.
      However, the pixel-to-pixel root mean square noise is often of the order of one
      pH unit. This comparatively high level of noise has its origin in photon quantum
      noise. pH measurements on living cells show a systematic deviation from expected
      values. This discrepancy appears to be the result of fluorophore interaction with
      various cell constituents, and is the subject of further investigation.

PMID- 10947904
TI  - Advantages of stereo imaging of metallic surfaces with low voltage backscattered
      electrons in a field emission scanning electron microscope
AB  - High emission current backscattered electron (HC-BSE) stereo imaging at low
      accelerating voltages (</= 5 keV) using a field emission scanning electron
      microscope was used to display surface structure detail. Samples of titanium with
      high degrees of surface roughness, for potential medical implant applications,
      were imaged using the HC-BSE technique at two stage tilts of + 3 degrees and - 3
      degrees out of the initial position. A digital stereo image was produced and
      qualitative height, depth and orientation information on the surface structures
      was observed. HC-BSE and secondary electron (SE) images were collected over a
      range of accelerating voltages. The low voltage SE and HC-BSE stereo images
      exhibited enhanced surface detail and contrast in comparison to high voltage (>
      10 keV) BSE or SE stereo images. The low voltage HC-BSE stereo images displayed
      similar surface detail to the low voltage SE images, although they showed more
      contrast and directional sensitivity on surface structures. At or below 5 keV,
      only structures a very short distance into the metallic surface were observed. At
      higher accelerating voltages a greater appearance of depth could be seen but
      there was less information on the fine surface detail and its angular
      orientation. The combined technique of HC-BSE imaging and stereo imaging should
      be useful for detailed studies on material surfaces and for biological samples
      with greater contrast and directional sensitivity than can be obtained with
      current SE or BSE detection modes.

PMID- 10947905
TI  - Peculiarities of imaging one- and two-dimensional structures in an emission
      electron microscope. 1. theory
AB  - Local changes in work function cause deviations of the electrical microfield near
      a sample surface as a result of the uniform accelerating field distribution
      between the sample (cathode) and the extractor electrode (anode). This results in
      a change in the electron trajectories. As a consequence, the microscope image
      shows remarkable changes in position, size, intensity and lateral resolution of
      distinct details, which can be quantitatively described by the calculations
      presented here. Analysing these effects in the image gives an opportunity to
      determine the real lateral size of the observed structures and the distribution
      of local contact potentials.

PMID- 10947906
TI  - Transmission electron microscopy of semiconductor quantum dots
AB  - We report on plan-view transmission electron microscopy techniques, by which the
      size, the actual shape and the strain of a coherent quantum dot in semiconductor
      heterostuctures can be measured very accurately. The bright-field suppressed
      diffraction imaging condition where no strong diffracted beam is excited in the
      sample provides reliable size measurement. Using suppressed-diffraction imaging
      condition, the intensity contour in a coherent island is related to the height,
      and thus the detailed shape and the aspect ratio can be extracted. The strain
      contrast of a coherent island imaged using an exact two-beam dynamical
      diffraction condition is useful for strain measurement and the corresponding
      features is related to the shape of an island. The physical origins and accuracy
      of interpretation of the image contrast are discussed, using the simulations and
      experimental examples.

PMID- 10947907
TI  - Automatic image analysis methods for the determination of stereological
      parameters - application to the analysis of densification during solid state
      sintering of WC-Co compacts
AB  - Automatic image analysis methods which were used to determine microstructural
      parameters of sintered materials are presented. Estimation of stereological
      parameters at interfaces, when the system contains more than two phases, is
      particularly detailed. It is shown that the specific surface areas and mean
      curvatures of the various interfaces can be estimated in the numerical space of
      the images. The methods are applied to the analysis of densification during solid
      state sintering of WC-Co compacts. The microstructural evolution is commented on.
      Application of microstructural measurements to the analysis of densification
      kinetics is also discussed.

PMID- 10947908
TI  - A new method for three-dimensional skeleton graph analysis of porous media:
      application to trabecular bone microarchitecture.
AB  - This paper introduces a new three-dimensional analysis of complex disordered
      porous media. Skeleton graph analysis is described and applied to trabecular bone
      images obtained by high resolution magnetic resonance imaging. This technique was
      developed bearing in mind topological considerations. The correspondence between
      vertices and branches of the skeleton graph and trabeculae is used in order to
      get local information on trabecular bone microarchitecture. In addition to real
      topological parameters, local structural information about trabeculae, such as
      length and volume distributions, are obtained. This method is applied to two sets
      of samples: six osteoporosis and six osteoarthritis bone samples. We demonstrate
      that skeleton graph analysis is a powerful technique to describe trabecular bone
      microarchitecture.

PMID- 10947910
TI  - Soluble P-selectin is not a surrogate marker for platelet P-selectin: evidence
      from a multicenter chest pain study group.
AB  - It has been reported that platelet expression and plasma levels of soluble P
      selectin are increased in patients with unstable coronary artery syndromes.
      However, the origin of soluble P-selectin remains unknown. We sought to determine
      whether platelet expression of P-selectin correlates with plasma levels in the
      population of patients presenting to the emergency department with chest pain. In
      338 patients presenting with chest pain to the emergency departments of three
      different hospitals, simultaneous soluble and platelet P-selection levels were
      determined using enzyme-linked immunosorbent assay (ELISA) and whole blood flow
      cytometry, respectively. Using regression analysis no correlation (R(2)=0.055)
      was found between soluble and platelet-bound P-selectin for the study population,
      including those patients with noncardiac chest pain (R(2)=0.019), unstable angina
      (R(2)=0.007), acute myocardial infraction (R(2)=0.033), congestive heart failure
      (R(2)=0.231), and gastrointestinal illness (R(2)=0.020). The platelet expression
      of P-selectin is unrelated to the level found in plasma in patients with acute
      chest pain, irrespective of the etiology of chest pain. Dissociation between
      platelet and soluble P-selectin suggests that the soluble form cannot serve as a
      surrogate marker to indicate platelet activation in the chest pain population.

PMID- 10947909
TI  - The use of the electrocardiogram to identify epicardial coronary and tissue
      reperfusion in acute myocardial infarction.
AB  - The standard 12-lead ECG gives us crucial information concerning myocardial
      perfusion and the success of reperfusion therapy for ST-elevation acute
      myocardial infarction. Continuous monitoring has advantages over repeated
      snapshot recordings. There are four electrocardiographic markers for prediction
      of the perfusion status of the ischemic myocardium: 1) ST-segment measurements;
      2) T-wave configuration; 3) QRS changes; and 4) reperfusion arrhythmias. Complete
      and stable (> or = 70%) resolution of ST-segment elevation is associated with
      better outcome and preservation of left ventricular function than partial (30% to
      70%) or no (< 30%) ST-segment resolution. Early inversion of the T-waves after
      initiation of reperfusion therapy is another marker of myocardial reperfusion and
      a good prognostic sign. Using standard 12-lead ECG, dynamic changes in Q-wave
      number, amplitude and width, R-wave amplitude and S-wave appearance are detected
      during reperfusion therapy. However, the significance of these changes have not
      been clarified. Reperfusion arrhythmias, especially bradycardia and accelerated
      idioventricular rhythm are detected occasionally during reperfusion therapy, but
      the value of reperfusion arrhythmias as a marker of coronary artery patency is
      still debatable. Dynamic changes in the QRS complexes, ST-segments and T-waves
      occur during reperfusion therapy and the days after. While changes in ST-segment
      amplitude have been extensively studied, the significance of QRS-complex and T
      wave changes are less clear, and especially whether changes in the QRS-complex
      and T-wave may be complementary and additive to ST-segment monitoring. It has
      remained unclear whether electrocardiographic signs of reperfusion and re
      ischemia should be used for therapeutic decision-making in the clinical setting.

PMID- 10947911
TI  - The decanucleotide polymorphism in the factor VII promoter predicts factor VII
      plasma levels but not the risk of acute coronary syndromes.
AB  - It is known from large epidemiological studies that the elevation of coagulation
      factor VII in plasma is an independent risk factor for acute coronary syndromes.
      The level of factor VII is influenced by polymorphic sites in the factor VII
      gene. However, data on the association of such polymorphisms with the risk of
      acute coronary syndromes are conflicting. A decanucleotide insertion/deletion
      polymorphic site has been described in the promoter of the factor VII gene that
      leads to a dramatic change in the plasma factor VII levels. We therefore analyzed
      the association of this polymorphism with the risk of acute coronary syndromes in
      a case-control study. Included in the study were 111 patients with
      angiographically documented acute coronary syndromes and 108 age- and sex-matched
      individuals from the same geographic area without signs or symptoms of coronary
      heart disease. The presence or absence of the decanucleotide stretch at position 
      323 in the promoter of factor VII was monitored using a polymerase chain reaction
      (PCR)-based restriction technique. The prevalence of the genotype with the
      homozygous deletion was similar in the patients with acute coronary syndromes
      (79.2%) and in the control patients (79.6%). There was a non-significant trend
      toward a higher prevalence of the homozygote deletion in patients with premature
      acute coronary syndromes (77.4%) compared with an age-matched subgroup of the
      control patients (67. 5%) (odds ratio [OR] 1.6, confidence interval [CI] 0.95,
      0.61-3.93). Thus, we could not find a significant association of the occurrence
      of acute coronary events with the insertion/deletion polymorphism in factor VII.

PMID- 10947912
TI  - Management of patients with prosthetic heart valves: potential impact of valve
      site, clinical characteristics, and comorbidity.
AB  - Nearly four decades have passed since the first mechanical prosthetic aortic
      valve was placed. Since then several design changes and modifications have been
      made to improve longevity and hemodynamics and reduce thrombogenicity. Despite
      these advances thromboembolism remains the major problem for mechanical
      prosthetic valves. The type and the position of the prosthetic valve and several
      clinical characteristics such as age greater than 70, atrial fibrillation,
      depressed left ventricular systolic function, left atrial enlargement, left
      atrial thrombus and a prior history of systemic embolization influence the risk
      of thromboembolism and the level of anticoagulation needed to prevent this
      complication. Through clinical experience guidelines have been developed by the
      American College of Chest Physicians to determine the optimal level of
      anticoagulation needed to lower the thromboembolic rate with an acceptable
      hemorrhagic event rate.

PMID- 10947914
TI  - Home monitoring and management of warfarin therapy: an anticoagulation clinic
      perspective.

PMID- 10947913
TI  - Platelet surface physiology and its importance in pharmacotherapy design and
      development: the adenosine diphosphate receptor antagonists.

PMID- 10947915
TI  - Emerging concepts in the diagnosis and management of venous thromboembolism
      during pregnancy.
AB  - Multiple changes in the coagulation system occur during pregnancy and account for
      the hypercoagulable state of pregnancy. Consequently, pregnant women are five
      times more likely to experience venous thromboembolism than non-pregnant women.
      Although the estimated rates of such events are low, venous thromboembolic
      disease is a leading cause of maternal death. The administration of intravenous
      or subcutaneous unfractionated heparin is the treatment and prophylaxis of
      choice. Warfarin is safe and efficacious following delivery, but should be
      avoided during pregnancy. LMWH is a promising alternative for treatment and
      prophylaxis, but further clinical experience is required.

PMID- 10947916
TI  - Inhibition of platelet-dependent prothrombinase activity and thrombin generation
      by glycoprotein IIb/IIIa receptor-directed antagonists: potential contributing
      mechanism of benefit in acute coronary syndromes.
AB  - The glycoprotein (GP) IIb/IIIa receptor antagonists used widely in the medical
      treatment of acute coronary syndromes and during percutaneous coronary
      interventions, prevent fibrinogen cross-linking and platelet aggregation,
      critical initiating steps in arterial thrombosis. Their anticoagulant properties,
      particularly when administered conjunctively with heparin preparations, are less
      well-characterized. In a series of in vitro studies, increasing concentrations of
      abciximab, tirofiban, and eptifibatide either alone or in combination with
      unfractionated heparin (UFH) or fractionated heparin (enoxaparin) were added to
      washed platelets suspended in Tyrode's buffer. Following platelet activation and
      prothrombinase assembly, thrombin generation was determined by enzyme-linked
      immunosorbent assay (ELISA). There was a concentration-dependent reduction in
      platelet-dependent thrombin generation with each of the GPIIb/IIIa receptor
      antagonists. The combination of tirofiban and UFH yielded percent, absolute and
      relative reductions (compared with tirofiban alone) of 48.0%, 16.9%, and 35.2%,
      respectively. The corresponding values for eptifibatide and abciximab were 38.0%,
      13.5%, 35.5%, and 55.1%, 3.8%, 8.4%, respectively. Thrombin generation was
      decreased by an additional 2 to 3% (absolute reduction) with high concentrations
      of enoxaparin in combination with either eptifibatide or abciximab. Platelet
      GPIIb/IIIa receptor antagonists, beyond their ability to prevent fibrinogen
      mediated aggregation, inhibit platelet-dependent prothrombinase activity and
      thrombin generation in a concentration-dependent manner. Heparin facilitates the
      existing anticoagulant properties, supporting combination therapy in clinical
      practice. The potential added benefit of fractionated heparin over UFH will
      require further investigation.

PMID- 10947917
TI  - Drip and ship: a new strategy for the treatment of acute coronary syndromes.
AB  - Glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway of platelet
      aggregation by preventing fibrinogen from binding to the GP IIb/IIIa platelet
      receptor. In patients with unstable angina (UA) or a non-Q wave myocardial
      infarction (NQWMI), including those with UA refractory to medical therapy, these
      agents decrease the risk of death, myocardial infarction (MI), and recurrent
      ischemia. Most patients with acute coronary syndromes are managed in hospitals
      without on-site angioplasty capabilities and often require transfer for an
      interventional procedure. We propose that GP IIb/IIIa inhibitors can be safely
      initiated at the referring hospital. We studied 20 patients with UA/NQWMI in whom
      therapy with a GP IIb/IIIa inhibitor, in addition to standard medical therapy,
      was initiated prior to transfer for an urgent percutaneous coronary intervention
      (PCI) ("drip and ship"). The primary end point was a composite of death, MI, and
      recurrent ischemia at 30 days. Twelve patients were treated with abciximab, 5
      patients were treated with tirofiban, and 3 patients initially treated with
      tirofiban were converted to abciximab. Procedural success occurred in 33 out of
      36 (92%) lesions and 18 out of 20 (90%) patients. At 30 days, 4 out of 20 (20%)
      patients had recurrent ischemia. The PTCA sites were widely patent in the 3
      patients who underwent repeat angiography. The fourth patient had an unsuccessful
      PCI and was referred for coronary artery bypass surgery. There were no MIs or
      deaths. Patients who require transfer for an urgent PCI can be managed safely and
      efficaciously by initiating a GP IIb/IIIa inhibitor, in addition to standard
      medical therapy, prior to transfer.

PMID- 10947918
TI  - Predictors of bleeding complications after rescue coronary interventions.
AB  - The purpose of this study was to determine predictors of bleeding complications
      after current rescue coronary interventions including stenting and adjunctive
      platelet inhibitors. Previous studies of rescue angioplasty for thrombolytic
      failure have identified variable rates of bleeding complications with balloon
      angioplasty alone. Although coronary stents and glycoprotein 2b/3a inhibitors
      have been shown to improve outcome in a wide variety of coronary interventions,
      the impact of these therapies on bleeding complications after rescue coronary
      intervention has not been determined. From 1996 through 1998, we treated 108
      consecutive patients with rescue coronary intervention (defined as attempted
      coronary intervention within 12 hours of thrombolysis for ongoing symptoms or
      electrocardiogram [ECG] changes) including conventional percutaneous transluminal
      coronary artery (PTCA), stenting (n = 45), and glycoprotein 2b/3a inhibitor use
      (n = 31). In-hospital clinical outcomes were obtained in all patients, and
      univariate and multivariate predictors of bleeding complications were identified.
      In hospital, moderate to severe bleeding complications occurred in 17.6% of the
      cohort, but the rate of severe bleeding complications (2.7%) and vascular repair
      (1.9%) were low. Independent predictors of bleeding complications were age > 60y,
      female gender, cardiogenic shock, and streptokinase use. Neither the delayed use
      of abciximab (on average 4 hours after thrombolytic therapy initiation) nor the
      use of rescue stenting were predictors of increased moderate to severe bleeding
      complications. Current rescue coronary intervention, including stents and
      platelet inhibitors, is associated with a low rate of severe bleeding
      complications. Moderate to severe bleeding complications were more common in
      selected subgroups of patients but not increased significantly by stenting or
      delayed abciximab use.

PMID- 10947920
TI  - Technical challenges in MR imaging of the cervical spine and cord.
AB  - In this article, the basic principles of image quality pertaining to cervical
      spine imaging and the impact of technical advancements on image quality are
      reviewed. The role of new MR pulse sequences and new applications of older
      sequences in evaluating abnormalities of the spinal cord, disks, joints, and
      bones of the cervical spine are discussed.

PMID- 10947921
TI  - Cervical spine: MR imaging techniques and anatomy.
AB  - MR imaging techniques of the cervical spine are reviewed. Cervical spine anatomy
      is described, with special attention given to the intervertebral disks, the
      arterial system, and the peripheral and central nervous systems. Anatomic
      structures are detailed on sagittal, axial, and coronal MR images.

PMID- 10947919
TI  - Stent thrombosis: historical perspectives and current trends.
AB  - Coronary stents are now implanted in more than 70% of percutaneous coronary
      revascularization procedures. Early enthusiasm for improved acute angiographic
      results and limited restenosis was dampened initially by a high rate of stent
      thrombosis and later by the increased bleeding complications of aggressive and
      complex anticoagulation protocols designed to lower the stent thrombosis risk.
      More recently, routine high-pressure deployment strategies and anti-platelet drug
      regimens have lowered the incidence of stent thrombosis to approximately 1%
      without an increased bleeding risk. The timing of stent thrombosis has also
      changed from a median of 4-5 days to a median of 1 day after the stent procedure.
      Risk factors in earlier studies included stenting for threatened or abrupt
      closure, smaller vessels, longer lesions, and possibly left anterior descending
      artery lesion location. Modern studies have shown a slightly increased risk for
      multiple stent use, residual dissection, and smaller final lumen. Optimal therapy
      for stent thrombosis includes emergent revascularization and anti-thrombotic
      treatment, although the clinical consequences remain dire despite successful
      reperfusion. The use of platelet glycoprotein IIb/IIIa inhibitors, especially in
      high-risk situations may further reduce the incidence of stent thrombosis.

PMID- 10947922
TI  - MR imaging of degenerative diseases in the cervical spine.
AB  - This article reviews three topics of fundamental importance in MR imaging of
      degenerative diseases in the cervical spine: (1) common clinical presentations
      that determine whether an MR examination is ordered and the ultimate significance
      ascribed to MR imaging results; (2) imaging techniques; and (3) MR imaging of the
      major types of cervical spine degeneration.

PMID- 10947924
TI  - MR imaging of bone tumors of the cervical spine.
AB  - MR Imaging has altered radically the detection, characterization, and the staging
      of bone tumors. This article reviews MR imaging techniques and appearances of
      benign and malignant bone tumors that are encountered in the cervical spine.

PMID- 10947923
TI  - MR imaging of arthritides of the cervical spine.
AB  - Indications for MR imaging have broadened with the development of multiplanar
      capability, superb soft tissue contrast, and high sensitivity for detecting
      pathologic alterations. These developments are especially valuable in the
      analysis of the spine, where multiple anatomic structures reside, each with
      varying physical properties. MR imaging is unsurpassed in demonstrating early
      structural and proliferative changes that occur in inflammatory and related
      arthritides, and in evaluating complications that can cause significant
      morbidity, and even death. The role of MR imaging in the evaluation of cervical
      spinal arthritis continues to evolve, as its role in identifying patients for
      surgical intervention becomes clearer.

PMID- 10947926
TI  - MR imaging of intrinsic inflammatory myelopathies.
AB  - The neuroimaging evaluation of patients with suspected inflammatory myelopathy is
      one of the more technically and interpretatively challenging MR examinations.
      This article reviews several recent MR imaging sequencing developments that have
      significantly improved spinal cord imaging. The clinical, pathologic, and MR
      imaging features of several of the more common inflammatory myelopathic-producing
      diseases also are discussed.

PMID- 10947925
TI  - MR imaging of intradural tumors of the cervical spine.
AB  - MR imaging is the modality of choice for intradural spinal tumors because of its
      unsurpassed depiction of soft tissues, the use of intravenous contrast, the
      absence of beam-hardening artifacts, and the ability to image in multiple planes.
      Intradural tumors are classified as intradural-extramedullary and intradural
      intramedullary. MR imaging techniques that best depict these tumors are reviewed,
      and several examples of tumors are described and illustrated.

PMID- 10947927
TI  - MR imaging of infections of the cervical spine.
AB  - Spine infections are serious clinical conditions that carry high morbidity and
      mortality rates. Cervical spine infections usually require a more aggressive
      medical and surgical approach than infections in the rest of the spine. Often,
      more than one anatomic structure or compartment becomes affected. Topics
      discussed in this article include incidence and predisposing factors of spine
      infections, types of micro-organisms involved in several disease conditions,
      pathophysiology and clinical manifestations, and imaging findings and MR imaging
      features.

PMID- 10947928
TI  - MR imaging of spinal cord vascular malformations with an emphasis on the cervical
      spine.
AB  - Spinal vascular malformations (AVMs) are rare but important causes of treatable
      myelopathies. Recent advances in interventional neuroradiolgy and neurosurgical
      techniques have improved the delineation and classifcation of these heterogeneous
      lesions. Because MR imaging usually is the first screening test for patients with
      myelopathy, the neuroradiologist must have a high level of knowledge of the
      common imaging characteristics of these lesions. This article reviews MR
      angiographic literature about spinal AVMs, reviews Type I-IV AVMs and cervical
      Type I AVMs, and describes their pathophysiology and common imaging
      characteristics, and elaborates on differences in cervical location from more
      typical positions.

PMID- 10947929
TI  - Contrast-enhanced MR angiography of spinal vessels.
AB  - Compared to routine spin-echo images, contrast-enhanced MR angiography provides
      improved characterization of the spinal vasculature. This technique can help
      narrow the differential diagnosis and guide further treatment in patients with
      radiculopathy or myelophathy. The most useful application to date has been in
      screening for spinal dural fistulae. The fast, three-dimensional method offers
      the possibility of distinguishing the largest spinal arteries and veins, although
      additional technical improvements and clinical experience are needed to
      accomplish this goal.

PMID- 10947930
TI  - MR imaging in cervical spine trauma.
AB  - This article emphasizes the technical aspects of MR imaging in acute cervical
      trauma, and details the specific protocols used at the authors' institution. A
      systematic approach to the evaluation of MR images in the trauma setting is
      discussed, and the role of MR imaging in the characterization of spinal cord
      injury and identification of spinal instability is defined. Correlations between
      MR imaging findings and patient functionality and outcome are outlined, and
      various classifications of cervical spine injuries are reviewed.

PMID- 10947931
TI  - MR imaging of the craniovertebral junction.
AB  - The rapid growth of MR imaging has brought a renewed interest in the
      craniovertebral junction. Many congenital and acquired lesions affect this region
      and compress the underlying cervicomedullary junction and cranial nerves. Basilar
      invagination, basilar impression, and cranial settling are readily assessed with
      MR imaging in the sagittal plane, and evaluation of this region on all cranial
      and cervical spine studies should become routine.

PMID- 10947932
TI  - MR diffusion imaging of the cervical spine.
AB  - Although diffusion-weighted imaging (DWI) of the brain has gained widespread
      clinical acceptance, DWI of the spine and spinal cord is less well known. This
      article briefly reviews some of the principles and concepts of diffusion imaging,
      including technical considerations with regard to in vivo DWI of the spine and
      spinal cord, and summarizes the research and clinical experience to date. With
      further development and refinement, DWI eventually may provide useful and
      important insight into a variety of diseases of the spine and spinal cord.

PMID- 10947933
TI  - Genome and gene therapy.

PMID- 10947934
TI  - Highlights from the third annual ASGT meeting. American Society of Gene Therapy.

PMID- 10947935
TI  - Globin gene therapy: one (seemingly) small vector change, one giant leap in
      optimism.

PMID- 10947936
TI  - A novel approach and a novel mechanism for stealthing gene delivery vehicles.

PMID- 10947937
TI  - Prolonged transgene expression mediated by a helper-dependent adenoviral vector
      (hdAd) in the central nervous system.
AB  - Conventional adenoviral vectors such as E1-deleted first-generation adenovirus
      (fgAd) elicit striking host immune response, resulting in limited expression of
      the transgene. A recently described helper-dependent, or gutless, adenoviral
      vector (hdAd) can promote stable transgene expression in peripheral organs,
      including the liver. We therefore investigated the safety and durability of hdAd
      mediated gene transfer to the central nervous system (CNS) of rats compared with
      gene delivery by fgAd. Equal amounts of either fgAd or hdAd carrying the beta geo
      transgene were stereotactically injected into the right hippocampus of adult
      rats. Transgene expression was assessed by histochemical staining, transgene
      stability by PCR analysis, and immune infiltration of T lymphocytes and
      macrophages by immunocytochemical methods. Strong transgene expression from
      either vector was detected in brain tissue examined on day 6 postinoculation.
      Thereafter, fgAd-mediated gene expression rapidly decreased, becoming
      undetectable by day 66, while expression from the hdAd vector persisted
      throughout the test period. PCR confirmed the presence of hdAd-associated DNA at
      66 days postinoculation. The hdAd injection elicited apparently lower numbers of
      brain-infiltrating macrophages and T cells than did administration of fgAd. These
      results indicate improved transgene expression and reduced immunogenicity with
      use of hdAd to deliver genes to the CNS.

PMID- 10947938
TI  - Effective treatment of experimental glioblastoma by HSV vector-mediated TNF alpha
      and HSV-tk gene transfer in combination with radiosurgery and ganciclovir
      administration.
AB  - Experiments were carried out in a nude mouse model of human glioblastoma to
      determine whether gamma-knife radiosurgery combined with herpes simplex virus
      thymidine kinase (tk) suicide gene therapy and tumor necrosis factor alpha
      (TNFalpha) gene transfer provided an improved multimodality treatment of this
      disease. Animals were inoculated intracerebrally with 2 x 10(5) U-87MG human
      glioblastoma cells to establish brain tumors. At 3 days postinoculation, the
      tumor region was injected with 2 x 10(6) infectious particles of highly defective
      herpes simplex viral vectors expressing the viral tk gene with the kinetics of a
      viral immediate early gene either alone (T.1) or together with TNF alpha
      (TH:TNF). Subgroups of animals were given daily intraperitoneal injections of
      ganciclovir (GCV) for 10 days and/or subjected to gamma-knife radiosurgery on the
      fifth day post tumor-cell implantation. Comparisons of animal survival showed
      that the TH:TNF vector in combination with radiosurgery and GCV administration
      provided the most effective therapy; eight of nine animals survived for 75 days
      compared to four of eight using the next best protocol. These findings suggest
      that gene therapy in combination with more conventional therapeutic methods may
      provide an improved strategy for extending the life expectancy of patients
      afflicted with this ultimately fatal disease.

PMID- 10947939
TI  - Soluble biodegradable polymer-based cytokine gene delivery for cancer treatment.
AB  - Transgene expression and tumor regression after direct injection of plasmid DNA
      encoding cytokine genes, such as mIL-12 and mIFN-gamma, remain very low. The
      objective of this study is to develop nontoxic biodegradable polymer-based
      cytokine gene delivery systems, which should enhance mIL-12 expression,
      increasing the likelihood of complete tumor elimination. We synthesized
      poly[alpha-(4-aminobutyl)-l-glycolic acid] (PAGA), a biodegradable nontoxic
      polymer, by melting condensation. Plasmids used in this study encoded luciferase
      (pLuc) and murine interleukin-12 (pmIL-12) genes. PAGA/plasmid complexes were
      prepared at different (+/-) charge ratios and characterized in terms of particle
      size, zeta potential, osmolality, surface morphology, and cytotoxicity.
      Polyplexes prepared by complexing PAGA with pmIL-12 as well as pLuc were used for
      transfection into cultured CT-26 colon adenocarcinoma cells as well as into CT-26
      tumor-bearing BALB/c mice. The in vitro and in vivo transfection efficiency was
      determined by luciferase assay (for pLuc), enzyme-linked immunosorbent assay (for
      mIL-12, p70, and p40), and reverse transcriptase-polymerase chain reaction (RT
      PCR) (for Luc and mIL-12 p35). PAGA condensed and protected plasmids from
      nuclease degradation. The mean particle size and zeta potential of the polyplexes
      prepared in 5% (w/v) glucose at 3:1 (+/-) charge ratio were approximately 100 nm
      and 20 mV, respectively. The surface characterization of polyplexes as determined
      by atomic force microscopy showed complete condensation of DNA with an
      ellipsoidal structure in Z direction. The levels of mIL-12 p40, mIL-12 p70, and
      mIFN-gamma were significantly higher for PAGA/pmIL-12 complexes compared to that
      of naked pmIL-12. This is in good agreement with RT-PCR data, which showed
      significant levels of mIL-12 p35 expression. The PAGA/pmIL-12 complexes did not
      induce any cytotoxicity in CT-26 cells as evidenced by 3-?4, 5-dimethylthiazol-2
      yl?-2,5-diphenyltetrazolium bromide assay and showed enhanced antitumor activity
      in vivo compared to naked pmIL-12. PAGA/pmIL-12 complexes are nontoxic and
      significantly enhance mIL-12 expression at mRNA and protein levels both in vitro
      and in vivo.

PMID- 10947940
TI  - The interactions of peptides with the innate immune system studied with use of T7
      phage peptide display.
AB  - The icosahedral T7 phage (diameter approximately 65 nm) displaying random
      peptides at the carboxy-terminus of the phage coat proteins was used as a model
      for drug and gene delivery vehicles containing peptide ligands. We found that
      displayed peptides were recognized by natural antibodies and induced complement
      activation. Strikingly, the phage inactivation by complement was peptide-specific
      that implied the existence of numerous natural antibodies with different peptide
      specificity. Selection of phage that avoided inactivation by complement allowed
      the identification of peptides that protected the phage by binding to serum
      proteins. In rat blood, peptides with carboxy-terminal lysine or arginine
      residues protected the phage against complement-mediated inactivation by binding
      C-reactive protein. In human serum, a number of protective peptides with tyrosine
      residues were selected. The recognition of displayed peptides by natural
      antibodies appears to represent a universal mechanism for activation of
      complement at sites that contain identical or homologous proteins with exposed
      carboxy-termini.

PMID- 10947941
TI  - Efficient nonviral cutaneous transfection.
AB  - Preclinical in vivo rodent, porcine, and primate experiments aimed at enhancing
      nonviral transgene delivery to skin have been performed. These investigations
      have identified a compound (aurintricarboxylic acid or ATA) that enhances
      transfection activity of "naked" plasmid and pulsed electrical fields
      (electroporation or EP) that synergistically boosts transgene expression to an
      average of 115-fold more than that observed with free DNA (P < 0.00009). When
      plasmid is intradermally injected with or without ATA, the transfected cells are
      typically restricted to the epidermis. However, when electroporation is added
      after the same injection, larger numbers of adipocytes and fibroblasts and
      numerous dendritic-like cells within the dermis and subdermal tissues are
      transfected. This advance creates new opportunities for cutaneous gene therapy
      and nucleic acid vaccine development.

PMID- 10947942
TI  - Adeno-associated virus mediates long-term gene transfer and delivery of
      chondroprotective IL-4 to murine synovium.
AB  - Treatments for rheumatoid arthritis and other inflammatory arthropathies are
      often ineffective at preventing joint destruction. Long-term genetic modification
      of the cells lining the joint space (synoviocytes) in vivo represents a potential
      method for the treatment of these chronic conditions. However, a vector capable
      of efficiently transducing synoviocytes in vivo for a persistent period has not
      been available. The present report describes the genetic modification of
      synoviocytes in vivo using recombinant adeno-associated virus. High-titer adeno
      associated virus encoding the gene for Escherichia coli beta-galactosidase was
      injected into the knee joints of mice. Synovial tissues were then examined for
      beta-galactosidase transgene expression by in situ staining and by fluorometry.
      High-efficiency, persistent transgene expression was observed in the synovium
      with no evidence of vector-induced inflammation. Expression was observed for at
      least 7 months and was higher in arthritic than nonarthritic mice. Gene transfer
      of murine IL-4 to the joints of mice with collagen-induced arthritis led to
      detectable levels of IL-4 in the joint and protection from articular cartilage
      destruction. These data suggest that adeno-associated virus may be a useful
      vector for gene delivery to the synovium for the treatment of inflammatory
      arthropathies.

PMID- 10947943
TI  - FGF2-Targeted adenovirus encoding platelet-derived growth factor-B enhances de
      novo tissue formation.
AB  - Gene therapy has yet to achieve reproducible clinical efficacy, due to inadequate
      gene delivery, inadequate gene expression, or dose-limiting toxicity. We have
      developed a gene therapy technology for tissue repair and regeneration that
      employs a structural matrix for DNA delivery. The matrix holds the DNA vector at
      the treatment site and provides a scaffolding for in-growth and accumulation of
      repair cells and efficient DNA transfection. We now report, for the first time,
      matrix-mediated delivery of targeted DNA vectors for soft tissue repair. A
      collagen matrix was used to deliver an adenoviral vector encoding platelet
      derived growth factor-B (AdPDGF-B), resulting in efficient transgene expression
      in vitro and in vivo. Increases in the overall levels of expression and in the
      relative amounts of secreted PDGF-BB were achieved when AdPDGF-B was conjugated
      to fibroblast growth factor (FGF2) such that the virus was targeted for cellular
      uptake via FGF receptors. Matrix-mediated delivery of AdPDGF-B enhanced wound
      healing responses in vivo, and FGF2 targeting generated effects comparable to
      nontargeted vectors at significantly lower doses. Therefore, matrix-mediated
      delivery in combination with FGF2 targeting overcomes some of the safety and
      efficacy limitations of current gene therapy strategies and is an attractive
      therapeutic approach for tissue repair and regeneration.

PMID- 10947944
TI  - The p53-independent tumoricidal activity of an adenoviral vector encoding a p27
      p16 fusion tumor suppressor gene.
AB  - We describe here that DE1-adenovirus vectors (AV) expressing a p27-p16 fusion
      molecule, termed W9, induce tumor cell apoptosis when overexpressed in a wide
      range of tumor cell types. However, in primary human cells derived from a variety
      of normal tissues, AV-W9 induced minimal apoptosis. In tumor cells AV-W9
      demonstrated 5- to 50-fold greater tumoricidal activity than either of the
      parental molecules p16 and p27. In these studies, AV-W9 elicited apoptosis
      independent of the p53 and Rb status of the tumor cells. In several murine tumor
      models AV-W9 demonstrated p53-independent antitumor activity. It completely
      prevented tumor formation in two ex vivo models, whereas the parental molecules
      resulted in partial protection. Furthermore, AV-W9 induced tumor regression or
      suppressed tumor growth when introduced intratumorally into preestablished tumors
      in mice. This effect may be mediated through tumor cell apoptosis or
      antiangiogenic activity of AV-W9. Thus, this novel chimeric molecule is more
      potent and capable of killing a broader spectrum of tumors than the parental p16
      and p27 molecules independent of the tumor cell p53 and phenotype and represents
      a powerful new therapeutic agent for cancer gene therapy.

PMID- 10947945
TI  - A stable system for the high-titer production of multiply attenuated lentiviral
      vectors.
AB  - Lentiviral vectors open exciting perspectives for the genetic treatment of a wide
      array of inherited and acquired diseases, owing to their ability to govern the
      efficient delivery, integration, and long-term expression of transgenes into
      nondividing cells both in vitro and in vivo. The genomic complexity of HIV, where
      a whole set of genes encode virulence factors essential for pathogenesis but not
      required for gene transfer, allowed a major step toward clinical acceptability
      through the creation of multiply attenuated packaging systems. Until now,
      however, vector particles could only be produced by transient transfection
      because no high-output, stable packaging cell line was available that produced
      the latest generation of HIV-based vectors. Here we describe such a line, based
      on the doxycycline-repressible expression of HIV-1 Rev/Gag/Pol and of the
      vesicular stomatitis virus G envelope (VSV G) in 293 human embryonic kidney
      cells. Upon induction, the LVG clones can produce 1 to 20 HeLa-transducing units
      per cell per day for about a week, a yield that compares favorably with that of
      transiently transfected 293T cells. These virions exhibit functional properties
      similar to those of viruses produced transiently, in particular the ability to
      transduce nonmitotic targets. This system will facilitate the further development
      of lentiviral vectors for gene therapy.

PMID- 10947946
TI  - The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage
      diseases indicates some genotype-phenotype correlation.
AB  - Lysosomal free sialic acid-storage diseases include the allelic disorders Salla
      disease (SD) and infantile sialic acid-storage disease (ISSD). The defective
      gene, SLC17A5, coding for the lysosomal free sialic acid transporter was recently
      isolated by positional cloning. In the present study, we have identified a large
      number of mutations in SLC17A5 in patients presenting with either Salla disease
      or the ISSD phenotype. We also report for the first time the exon-intron
      boundaries of SLC17A5. All Finnish patients with SD (n=80) had a missense
      mutation changing a highly conserved arginine to cysteine (R39C); 91% of them
      were homozygotes for this old founder mutation. The compound-heterozygote
      patients, with the founder mutation in only one allele, presented with a more
      severe phenotype than did the homozygote patients. The same R39C mutation was
      also found both in most of the Swedish patients with SD and in a heterozygous
      form in five patients from central Europe who presented with an unusually severe
      (intermediate) SD phenotype. Ten different mutations, including deletions,
      insertions, and missense and nonsense mutations, were identified in patients with
      the most severe ISSD phenotype, most of whom were compound heterozygotes. Our
      results indicate some genotype-phenotype correlation in free sialic acid-storage
      diseases, suggesting that the phenotype associated with the homozygote R39C
      mutation is milder than that associated with other mutations.

PMID- 10947948
TI  - Comparison of the kinetic properties of the lipid- and protein-kinase activities
      of the p110alpha and p110beta catalytic subunits of class-Ia phosphoinositide 3
      kinases.
AB  - Growth factors regulate a wide range of cellular processes via activation of the
      class-Ia phosphoinositide 3-kinases (PI 3-kinases). We directly compared kinetic
      properties of lipid- and protein-kinase activities of the widely expressed
      p110alpha and p110beta isoforms. The lipid-kinase activity did not display
      Michaelis-Menten kinetics but modelling the kinetic data demonstrated that
      p110alpha has a higher V(max) and a 25-fold higher K(m) for PtdIns than p110beta.
      A similar situation occurs with PtdIns(4,5)P(2), because at low concentration of
      PtdIns(4,5)P(2) p110beta is a better PtdIns(4,5)P(2) kinase than p110alpha,
      although this is reversed at high concentrations. These differences suggest
      different functional roles and we hypothesize that p110beta functions better in
      areas of membranes containing low levels of substrate whereas p110alpha would
      work best in areas of high substrate density such as membrane lipid rafts. We
      also compared protein-kinase activities. We found that p110beta phosphorylated
      p85 to a lower degree than did p110alpha. We used a novel peptide-based assay to
      compare the kinetics of the protein-kinase activities of p110alpha and p110beta.
      These studies revealed that, like the lipid-kinase activity, the protein-kinase
      activity of p110alpha has a higher K(m) (550 microM) than p110beta (K(m) 8
      microgM). Similarly, the relative V(max) towards peptide substrate of p110alpha
      was three times higher than that of p110beta. This implies differences in the
      rates of regulatory autophosphorylation in vivo, which are likely to mean
      differential regulation of the lipid-kinase activities of p110alpha and p110beta
      in vivo.

PMID- 10947947
TI  - Sac phosphatase domain proteins.
AB  - Advances in our understanding of the roles of phosphatidylinositol phosphates in
      controlling cellular functions such as endocytosis, exocytosis and the actin
      cytoskeleton have included new insights into the phosphatases that are
      responsible for the interconversion of these lipids. One of these is an entirely
      novel class of phosphatase domain found in a number of well characterized
      proteins. Proteins containing this Sac phosphatase domain include the yeast
      Saccharomyces cerevisiae proteins Sac1p and Fig4p. The Sac phosphatase domain is
      also found within the mammalian phosphoinositide 5-phosphatase synaptojanin and
      the yeast synaptojanin homologues Inp51p, Inp52p and Inp53p. These proteins
      therefore contain both Sac phosphatase and 5-phosphatase domains. This review
      describes the Sac phosphatase domain-containing proteins and their actions, with
      particular reference to the genetic and biochemical insights provided by study of
      the yeast Saccharomyces cerevisiae.

PMID- 10947949
TI  - L-leucine availability regulates phosphatidylinositol 3-kinase, p70 S6 kinase and
      glycogen synthase kinase-3 activity in L6 muscle cells: evidence for the
      involvement of the mammalian target of rapamycin (mTOR) pathway in the L-leucine
      induced up-regulation of system A amino acid transport.
AB  - Amino acid availability is known to regulate diverse cell processes including the
      activation of p70 S6 kinase, initiation factors involved in mRNA translation,
      gene expression and cellular amino acid uptake. Essential amino acids, in
      particular the branched-chain amino acids (e.g. leucine), have been shown to be
      the dominant players in mediating these effects, although the precise nature by
      which they regulate these processes remain poorly understood. In this study we
      have investigated the mechanisms involved in the leucine-induced modulation of
      p70 S6 kinase and addressed whether this kinase participates in the up-regulation
      of the System A amino acid transporter in L6 muscle cells. Incubation of muscle
      cells that had been amino acid-deprived for 1 h with L-leucine (2 mM) led to a
      rapid (>2-fold) activation of p70 S6 kinase, which was suppressed by both
      wortmannin and rapamycin. Consistent with this finding, addition of leucine
      caused a rapid ( approximately 5-fold) but transient stimulation of
      phosphatidylinositol 3-kinase (PI3K). PI3K activation was inhibited by wortmannin
      and was not dependent upon insulin receptor substrate-1 activation. Unlike
      stimulation by insulin, activation of neither protein kinase B nor p42/p44
      mitogen-activated protein kinase accompanied the leucine-induced stimulation of
      PI3K. However, the leucine-induced activation of PI3K and p70 S6 kinase did
      result in the concomitant inactivation of glycogen synthase kinase-3 (GSK-3).
      Leucine enhanced System A transport by approximately 50%. We have shown
      previously that this stimulation is protein-synthesis-dependent and in the
      current study we show that it was blocked by both wortmannin and rapamycin. Our
      findings indicate that PI3K and the mammalian target of rapamycin are components
      of a nutrient signalling pathway that regulates the activation of p70 S6 kinase
      and induction of System A in L6 cells. The activation of this pathway by leucine
      is also responsible for the inactivation of GSK-3, and this is likely to have
      important regulatory implications for translation initiation.

PMID- 10947950
TI  - Cloning, post-translational modifications, heterologous expression and ligand
      binding of boar salivary lipocalin.
AB  - Boar submaxillary glands produce the sex-specific salivary lipocalin (SAL), which
      binds steroidal sex pheromones as endogenous ligands. The cDNA encoding SAL was
      cloned and sequenced. From a single individual, two protein isoforms, differing
      in three amino acid residues, were purified and structurally characterized by a
      combined Edman degradation/MS approach. These experiments ascertained that the
      mature polypeptide is composed of 168 amino acid residues, that one of the three
      putative glycosylation sites is post-translationally modified and the structure
      of the bound glycosidic moieties. Two of the cysteine residues are paired
      together in a disulphide bridge, whereas the remaining two occur as free thiols.
      SAL bears sequence similarity to other lipocalins; on this basis, a three
      dimensional model of the protein has been built. A SAL isoform was expressed in
      Escherichia coli in good yields. Protein chemistry and CD experiments verified
      that the recombinant product shows the same redox state at the cysteine residues
      and that the same conformation is observed as in the natural protein, thus
      suggesting similar folding. Binding experiments on natural and recombinant SAL
      were performed with the fluorescent probe 1-aminoanthracene, which was
      efficiently displaced by the steroidal sex pheromone, as well as by several
      odorants.

PMID- 10947951
TI  - Age-related accumulation of Maillard reaction products in human articular
      cartilage collagen.
AB  - Non-enzymic modification of tissue proteins by reducing sugars, the so-called
      Maillard reaction, is a prominent feature of aging. In articular cartilage,
      relatively high levels of the advanced glycation end product (AGE) pentosidine
      accumulate with age. Higher pentosidine levels have been associated with a
      stiffer collagen network in cartilage. However, even in cartilage, pentosidine
      levels themselves represent <1 cross-link per 20 collagen molecules, and as such
      cannot be expected to contribute substantially to the increase in collagen
      network stiffness. In the present study, we investigated a broad range of
      Maillard reaction products in cartilage collagen in order to determine whether
      pentosidine serves as an adequate marker for AGE levels. Not only did the well
      characterized AGEs pentosidine, N(epsilon)-(carboxymethyl)lysine, and N(epsilon)
      (carboxyethyl)lysine increase with age in cartilage collagen (all P<0.0001), but
      also general measures of AGE cross-linking, such as browning and fluorescence
      (both P<0.0001), increased. The levels of these AGEs are all higher in cartilage
      collagen than in skin collagen. As a functional measure of glycation the
      digestibility of articular collagen by bacterial collagenase was investigated;
      digestibility decreased linearly with age, proportional to the extent of
      glycation. Furthermore, the arginine content and the sum of the hydroxylysine and
      lysine content of cartilage collagen decrease significantly with age (P<0.0001
      and P<0. 01 respectively), possibly due to modification by the Maillard reaction.
      The observed relationship between glycation and amino acid modification has not
      been reported previously in vivo. Our present results indicate that extensive
      accumulation of a variety of Maillard reaction products occurs in cartilage
      collagen with age. Altogether our results support the hypothesis that glycation
      contributes to stiffer and more brittle cartilage with advancing age.

PMID- 10947952
TI  - Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c)
      transcriptional activity in rat hepatocytes.
AB  - The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c)
      plays a major role in the effect of insulin on the transcription of hepatic genes
      such as glucokinase and fatty acid synthase. We show here in cultured rat
      hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase
      pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic
      reticulum. This precursor form is then rapidly cleaved, possibly irrespective of
      the continuous presence of insulin, leading to an increased content of the
      nuclear mature form of SREBP-1c. Nevertheless, the increased amount of the mature
      form of SREBP-1c in the nucleus is not a prerequisite for the rapid effect of
      insulin on the transcription of genes such as glucokinase, suggesting that
      additional actions of the hormone are involved, such as the activation of the
      nuclear form of SREBP-1c or of an unidentified SREBP-1c partner.

PMID- 10947953
TI  - A novel transcriptional factor with Ser/Thr kinase activity involved in the
      transforming growth factor (TGF)-beta signalling pathway.
AB  - Transforming growth factor-beta (TGF-beta) shows a variety of biological
      activities in various organs or cells. Recently some factors such as Smads (Sma
      and Mad proteins) and TGF-beta activating kinase 1 ('TAK1') have been
      characterized as signalling molecules downstream of TGF-beta. Several TGF-beta
      response elements have been identified such as cAMP response element, Smad
      binding element, and recognition sites for activating protein-1 and stimulating
      protein-1 in various gene promoters. We also reported a TGF-beta response element
      in the human C-type natriuretic peptide (CNP) gene promoter. In this paper, we
      report on a novel factor which regulates the TGF-beta response promoter. This
      factor, named TSF1 (TGF-beta stimulated factor 1), possessed DNA-binding ability
      and activated the TGF-beta responsive CNP promoter or vascular endothelial growth
      factor gene promoter which possesses a sequence element analogous to the TGF-beta
      responsive GC-rich element of the CNP promoter. TSF1 did not directly activate a
      Smads-dependent promoter from plasminogen activator inhibitor 1 gene, but it
      showed enhancement in co-operation with Smad3 and Smad4. Interestingly, this
      factor had the structural features of a Ser/Thr kinase and actually exhibited
      protein kinase activity. TSF1 mRNA as well as its protein level were stimulated
      by TGF-beta treatment. Thus, TSF1 is an unique factor with two biological
      functions, transcriptional regulation and protein phosphorylation, that may be
      involved in TGF-beta signals.

PMID- 10947954
TI  - Polymorphism of the glutathione transferase subunit 3 in Sprague-Dawley rats
      involves a reactive cysteine residue.
AB  - Comparison of Hirosaki hairless rat (HHR) and Sprague-Dawley (SD) rat liver
      glutathione transferase (GST) subunits by HPLC revealed differences in subunit 3;
      a new peak was detected in HHR GSTs and this was tentatively named X. By
      chromatofocusing, the HHR GST form composed of peak X and SD rat GST 3-3 were
      eluted at pH 8.8 and 9.1 respectively. The former was more sensitive to the SH
      reagent N-ethylmaleimide (NEM) than the latter. GSSG treatment of peak X resulted
      in a shift of retention time (peak Y) by HPLC analysis. However, such conversion
      was not observed for the SD rat GST 3-3 following GSSG or dithiothreitol (DTT)
      treatment. Peak Y exhibited m/z values of 26091.9 and 26125.4 by matrix-assisted
      laser-desorption ionization-time-of-flight MS, higher than those of peak X by 304
      307, equivalent to the molecular-mass value of GSH. On treatment with DTT, peak Y
      was converted into peak X, with release of a substance with HPLC-characteristics
      of GSH. This substance was confirmed to be GSH by liquid chromatography/MS. These
      results thus indicated peak Y to be a glutathionylated form of peak X.
      Quantification revealed the release of 4 nmol of GSH from 0.12 mg of the peak Y
      protein, corresponding to 4.8 nmol (M(r) 25000). The nucleotide sequence of HHR
      GST subunit 3 cDNA proved identical to that reported for pGTA/C44, possessing
      asparagine and cysteine as the 198th and 199th amino acid residues, respectively,
      corresponding to lysine and serine in subunit 3 of the SD rat. Thus peak X
      appeared to be the product of HHR GST subunit 3 cDNA. Treatment with N-(4
      dimethylamino-3,5-dinitrophenyl)maleimide, a coloured analogue of NEM, followed
      by trypsin-treatment and sequencing of labelled peptides, identified the reactive
      cysteine residue of HHR GST subunit 3 to be located at position 199. Unlike SD
      rat GST 3-3, HHR GST 3-3 was not activated by treatment with xanthine and
      xanthine oxidase. These results suggest polymorphism of the rat GST subunit 3
      gene with individual gene product variation in sensitivity to oxidative stress.

PMID- 10947956
TI  - Characterization of a cDNA encoding RP43, a CUB-domain-containing protein from
      the tube of Riftia pachyptila (Vestimentifera), and distribution of its
      transcript.
AB  - A major 43 kDa protein from the protective tube of Riftia pachyptila
      (Vestimentifera), named RP43, was partly microsequenced after isolation by
      SDS/PAGE from the protein fraction of tubes collected around the hydrothermal
      vents at the East Pacific Rise. On the basis of the partial peptide sequences
      obtained, experiments using reverse-transcriptase-mediated PCR and rapid
      amplification of cDNA ends led to the complete cDNA sequence. Analysis of deduced
      amino acid sequence of RP43 showed the presence of CUB domains (100-110-residue
      spanning domains first reported in the complement subcomponents C1r/C1s,
      epidermal-growth-factor-related sea urchin protein and bone morphogenetic protein
      1) that seem to be involved in protein-protein and glycosaminoglycan-protein
      interactions. This peculiarity strongly suggests that RP43 might have a crucial
      role in tightening the different elements of the worm tube. However, the absence
      of chitin-binding motifs inclines us to favour a role in protein-protein
      interactions during assembly of the tube components. The RP43 mRNA was found to
      be present in specific epidermal cells from the worm body wall but never in the
      chitin-synthesizing gland cells. This unexpected result clearly indicates that
      the major tube protein is synthesized in specialized areas of the outer
      epithelium and that at least two different tissues are involved in the synthesis
      of the exoskeleton.

PMID- 10947955
TI  - Cross-talk between receptors with intrinsic tyrosine kinase activity and alpha1b
      adrenoceptors.
AB  - The effect of epidermal growth factor (EGF) and platelet-derived growth factor
      (PDGF) on the phosphorylation and function of alpha(1b)-adrenoceptors transfected
      into Rat-1 fibroblasts was studied. EGF and PDGF increased the phosphorylation of
      these adrenoceptors. The effect of EGF was blocked by tyrphostin AG1478 and that
      of PDGF was blocked by tyrphostin AG1296, inhibitors of the intrinsic tyrosine
      kinase activities of the receptors for these growth factors. Wortmannin, an
      inhibitor of phosphoinositide 3-kinase, blocked the alpha(1b)-adrenoceptor
      phosphorylation induced by EGF but not that induced by PDGF. Inhibition of
      protein kinase C blocked the adrenoceptor phosphorylation induced by EGF and
      PDGF. The ability of noradrenaline to increase [(35)S]guanosine 5'-[gamma
      thio]triphosphate ([(35)S]GTP[S]) binding in membrane preparations was used as an
      index of the functional coupling of the alpha(1b)-adrenoceptors and G-proteins.
      Noradrenaline-stimulated [(35)S]GTP[S] binding was markedly decreased in
      membranes from cells pretreated with EGF or PDGF. Our data indicate that: (i)
      activation of EGF and PDGF receptors induces phosphorylation of alpha(1b)
      adrenoceptors, (ii) phosphatidylinositol 3-kinase is involved in the EGF
      response, but does not seem to play a major role in the action of PDGF, (iii)
      protein kinase C mediates this action of both growth factors and (iv) the
      phosphorylation of alpha(1b)-adrenoceptors induced by EGF and PDGF is associated
      with adrenoceptor desensitization.

PMID- 10947958
TI  - Physiological oxygen tensions modulate expression of the mdr1b multidrug
      resistance gene in primary rat hepatocyte cultures.
AB  - P-Glycoprotein transporters encoded by mdr1 (multidrug resistance) genes mediate
      extrusion of an array of lipophilic xenobiotics from the cell. In rat liver, mdr
      transcripts have been shown to be expressed mainly in hepatocytes of the
      periportal region. Since gradients in oxygen tension (pO(2)) may contribute
      towards zonated gene expression, the influence of arterial and venous pO(2) on
      mRNA expression of the mdr1b isoform was examined in primary rat hepatocytes
      cultured for up to 3 days. Maximal mdr1b mRNA levels (100%) were observed under
      arterial pO(2) after 72 h, whereas less than half-maximal mRNA levels (40%) were
      attained under venous pO(2). Accordingly, expression of mdr protein and extrusion
      of the mdr1 substrate rhodamine 123 were maximal under arterial pO(2) and reduced
      under venous pO(2). Oxygen-dependent modulation of mdr1b mRNA expression was
      prevented by actinomycin D, indicating transcriptional regulation. Inhibition of
      haem synthesis by 25 microM CoCl(2) blocked mdr1b mRNA expression under both
      oxygen tensions, whereas 80 microM desferrioxamine abolished modulation by O(2).
      Haem (10 microM) increased mdr1b mRNA levels under arterial and venous pO(2). In
      hepatocytes treated with 50 microM H(2)O(2), mdr1b mRNA expression was elevated
      by about 1.6-fold at venous pO(2) and 1.5-fold at arterial pO(2). These results
      support the conclusion that haem proteins are crucial for modulation of mdr1b
      mRNA expression by O(2) in hepatocyte cultures and that reactive oxygen species
      may participate in O(2)-dependent signal transduction. Furthermore, the present
      study suggests that oxygen might be a critical modulator for zonated secretion of
      mdr1 substrates into the bile.

PMID- 10947957
TI  - Human sphingosine kinase: purification, molecular cloning and characterization of
      the native and recombinant enzymes.
AB  - Sphingosine 1-phosphate (S1P) is a novel lipid messenger that has important roles
      in a wide variety of mammalian cellular processes including growth,
      differentiation and death. Basal levels of S1P in mammalian cells are generally
      low, but can increase rapidly and transiently when cells are exposed to mitogenic
      agents and other stimuli. This increase is largely due to increased activity of
      sphingosine kinase (SK), the enzyme that catalyses its formation. In the current
      study we have purified, cloned and characterized the first human SK to obtain a
      better understanding of its biochemical activity and possible activation
      mechanisms. The enzyme was purified to homogeneity from human placenta using
      ammonium sulphate precipitation, anion-exchange chromatography, calmodulin
      affinity chromatography and gel-filtration chromatography. This resulted in a
      purification of over 10(6)-fold from the original placenta extract. The enzyme
      was cloned and expressed in active form in both HEK-293T cells and Escherichia
      coli, and the recombinant E. coli-derived SK purified to homogeneity. To
      establish whether post-translational modifications lead to activation of human SK
      activity we characterized both the purified placental enzyme and the purified
      recombinant SK produced in E. coli, where such modifications would not occur. The
      premise for this study was that post-translational modifications are likely to
      cause conformational changes in the structure of SK, which may result in
      detectable changes in the physico-chemical or catalytic properties of the enzyme.
      Thus the enzymes were characterized with respect to substrate specificity and
      kinetics, inhibition kinetics and various other physico-chemical properties. In
      all cases, both the native and recombinant SKs displayed remarkably similar
      properties, indicating that post-translational modifications are not required for
      basal activity of human SK.

PMID- 10947959
TI  - Stanniocalcin 1 and 2 are secreted as phosphoproteins from human fibrosarcoma
      cells.
AB  - Stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) are two recently identified
      mammalian peptide hormones. STC1 plays a role in calcium and phosphate
      homoeostasis, while the role of STC2 is unknown. We examined a human fibrosarcoma
      cell line, HT1080, that has high steady-state STC1 and STC2 mRNA levels, to
      determine whether these proteins are secreted. Following incubation of HT1080
      cells with (32)P, labelled STC1 and STC2 were found to be secreted into the
      medium. STC1 was phosphorylated in vitro by protein kinase C (PKC). In vitro and
      in vivo phosphorylation both occurred exclusively on serine and the
      phosphopeptide maps were similar, suggesting that PKC might be the in vivo
      kinase. STC2 was phosphorylated in vitro by casein kinase II (CK2), in vitro and
      in vivo phosphorylation were exclusively on serine and the phosphopeptide maps
      were indistinguishable. Phosphorylation of STC2 in intact cells resulted from the
      action of an ecto-protein kinase, since exogenous STC2 was phosphorylated by
      HT1080 cells and no phosphorylated STC2 was detectable inside the cells. The
      ectokinase activity was abolished by heparin and GTP could substitute for ATP as
      the phosphate donor, indicative of an ecto-CK2-like activity. The in vitro CK2
      phosphorylation site was shown by matrix-assisted laser-desorption ionization
      time-of-flight MS to be a single serine located between Ser-285 and Ser-298 in
      the C-terminal region of STC2. This is the first report of the secretion of STC1
      or STC2 from mammalian cells. We conclude that these human fibrosarcoma cells
      express both STC1 and STC2 as secreted phosphoproteins in vivo, with STC2 being
      phosphorylated by an ecto-CK2-like enzyme.

PMID- 10947960
TI  - Purification of Golgi casein kinase from bovine milk.
AB  - Caseins and many other secretory proteins are phosphorylated during their
      transport through the secretory pathway by a protein kinase present within Golgi
      compartments. Molecular analysis of the Golgi casein kinase (GCK) has not been
      possible since it has not been purified to homogeneity or been cloned. Previous
      attempts have been made to purify GCK activity from mammary gland Golgi
      fractions, but these have not resulted in extensive purification of the enzyme.
      In the present study, we have demonstrated that substantial amounts of GCK
      activity, assayed using a specific peptide substrate, can be detected as a
      soluble form in bovine milk, and we have used milk as a source for purification.
      A purification protocol was established that allowed>80000-fold purification to a
      specific activity of GCK (approx. 700 nmoles/min per mg of protein) far higher
      than previously achieved. These findings cast doubts on previous claims for
      purification of GCK activity. In addition, ion-exchange chromatography resolved
      two closely eluting peaks of activity, suggesting the existence of two related,
      but distinct, GCK activities.

PMID- 10947961
TI  - Platelet-derived-growth-factor-induced signalling in human platelets:
      phosphoinositide-3-kinase-dependent inhibition of platelet activation.
AB  - Human platelets release platelet-derived growth factor (PDGF) from alpha-granules
      during platelet activation. We have previously shown that platelets have PDGF
      alpha-receptors, a transmembrane tyrosine kinase that takes part in negative
      feedback regulation during platelet activation. Here we have described a study of
      PDGF-induced tyrosine phosphorylation of platelet substrates and phosphoinositide
      3-kinase (PI-3K) activity in collagen-stimulated platelets. By immunoblotting
      with phosphotyrosine antibodies of collagen-activated platelets we found that
      PDGF increased the phosphorylation of several platelet substrates, e.g. pp140,
      pp120 and pp85. PDGF inhibited collagen-induced platelet activation in the
      presence of inhibitors of autocrine stimulation, thus blocking the pure collagen
      induced signal transduction. PDGF enhanced the collagen-induced formation of
      PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) as measured by HPLC. Wortmannin and
      LY294002, two unrelated inhibitors of PI-3K, were used to investigate the role of
      PI-3K in PDGF-induced platelet signalling. Incubation of platelets with
      wortmannin and LY294002 blocked the formation of three phosphorylated inositides
      as well as the inhibitory effect of PDGF on collagen-induced platelet activation.
      We conclude that the inhibitory effect of PDGF on platelet activation is PI-3K
      dependent. This is the first demonstration of a negative regulatory function of 3
      phosphorylated inositides in platelets.

PMID- 10947962
TI  - New type of starch-binding domain: the direct repeat motif in the C-terminal
      region of Bacillus sp. no. 195 alpha-amylase contributes to starch binding and
      raw starch degrading.
AB  - The alpha-amylase from Bacillus sp. no. 195 (BAA) consists of two domains: one is
      the catalytic domain similar to alpha-amylases from animals and Streptomyces in
      the N-terminal region; the other is the functionally unknown domain composed of
      an approx. 90-residue direct repeat in the C-terminal region. The gene coding for
      BAA was expressed in Streptomyces lividans TK24. Three active forms of the gene
      products were found. The pH and thermal profiles of BAAs, and their catalytic
      activities for p-nitrophenyl maltopentaoside and soluble starch, showed almost
      the same behaviours. The largest, 69 kDa, form (BAA-alpha) was of the same
      molecular mass as that of the mature protein estimated from the nucleotide
      sequence, and had raw-starch-binding and -degrading abilities. The second
      largest, 60 kDa, form (BAA-beta), whose molecular mass was the same as that of
      the natural enzyme from Bacillus sp. no. 195, was generated by proteolytic
      processing between the two repeat sequences in the C-terminal region, and had
      lower activities for raw starch binding and degrading than those of BAA-alpha.
      The smallest, 50 kDa, form (BAA-gamma) contained only the N-terminal catalytic
      domain as a result of removal of the C-terminal repeat sequence, which led to
      loss of binding and degradation of insoluble starches. Thus the starch adsorption
      capacity and raw-starch-degrading activity of BAAs depends on the existence of
      the repeat sequence in the C-terminal region. BAA-alpha was specifically adsorbed
      on starch or dextran (alpha-1,4 or alpha-1,6 glucan), and specifically desorbed
      with maltose or beta-cyclodextrin. These observations indicated that the repeat
      sequence of the enzyme was functional in the starch-binding domain (SBD). We
      propose the designation of the homologues to the SBD of glucoamylase from
      Aspergillus niger as family I SBDs, the homologues to that of glucoamylase from
      Rhizopus oryzae as family II, and the homologues of this repeat sequence of BAA
      as family III.

PMID- 10947965
TI  - Functional analysis of tumour necrosis factor-alpha-related apoptosis-inducing
      ligand (TRAIL): cysteine-230 plays a critical role in the homotrimerization and
      biological activity of this novel tumoricidal cytokine.
AB  - We have determined that the mutation of the cysteine-230 residue to either
      glycine or serine in TRAIL (tumour necrosis factor-alpha-related apoptosis
      inducing ligand) results in the formation of a structurally incompetent dimer and
      a consequent loss of apoptotic activity. Similarly, chemical modification of the
      thiol residues present in both reduced and Zn(2+)-depleted trimer converts TRAIL
      into an inactive dimer. We postulate that cysteine-230 plays a critical role in
      homotrimerization of this tumoricidal cytokine.

PMID- 10947964
TI  - The 72/74-kDa polypeptides of the 70-110 S large heterogeneous nuclear
      ribonucleoprotein complex (LH-nRNP) represent a discrete subset of the hnRNP M
      protein family.
AB  - Pre-mRNA processing in eukaryotes is thought to take place on a multitude of
      nuclear ribonucleoprotein (RNP) complexes, the most abundant of them being the
      heterogeneous nuclear (hn) RNP complexes. The identification in mammalian nuclear
      extracts of a novel, less-abundant 70-110 S heterogeneous RNP, named large
      heterogeneous nuclear RNP (LH-nRNP), has previously been reported by Aidinis,
      Sekeris and Guialis (1995) Nucleic Acids Res. 23, 2742-2753. The structural
      composition of the LH-nRNP complex has been determined following the production
      of polyclonal antibodies against the major protein constituents of the complex,
      the pair of the 72/74-kDa polypeptides. In the present study evidence is shown to
      prove that the 72/74-kDa proteins are members of the hnRNP M protein family,
      hereafter referred to as 72/74(M) polypeptides. The extensive application of two
      dimensional gel electrophoresis, combined with specific immunoprecipitation and
      immunoblotting assays, has allowed the assignment of the 72/74(M) proteins to a
      subset of the hnRNP M family, characteristic of the presence of the LH-nRNP
      complex and distinct from the hnRNP-associated M1-M4 components. Moreover, the
      immunoselection of the LH-nRNP complex from [(32)P]orthophosphate-labelled HeLa
      cells, with the parallel application of UV irradiation, has permitted the
      identification of the 72/74(M) polypeptides as the sole protein constituents of
      the complex in direct contact with the RNA. It is proposed that LH-nRNP
      constitutes a discrete subset of hnRNP complexes, having a possible role in
      establishing specific interactions between hnRNP and nuclear-matrix protein
      components.

PMID- 10947963
TI  - Monoclonal antibodies identify residues 199-216 of the integrin alpha2 vWFA
      domain as a functionally important region within alpha2beta1.
AB  - Integrin alpha2beta1 is the major receptor for collagens in the human body, and
      the collagen-binding site on the alpha2 subunit von Willebrand factor A-type
      domain (vWFA domain) is now well defined. However, the biologically important
      conformational changes that are associated with collagen binding, and the means
      by which the vWFA domain is integrated into the whole integrin are not completely
      understood. We have raised monoclonal antibodies against recombinant alpha2 vWFA
      domain for use as probes of function. Three antibodies, JA202, JA215 and JA218,
      inhibited binding to collagen, collagen I C-propeptide and E-cadherin,
      demonstrating that their function is important for structurally diverse
      alpha2beta1 ligands. Cross-blocking studies grouped the epitopes into two
      clusters: (I) JA202, the inhibitory antibody, Gi9, and a non-inhibitory antibody,
      JA208; (II) JA215 and JA218. Both clusters were sensitive to events at the
      collagen binding site, as binding of Gi9, JA202, JA215 and JA218 were inhibited
      by collagen peptide, JA208 binding was enhanced by collagen peptide, and binding
      of JA202 was decreased after mutagenesis of the cation-binding residue Thr(221)
      to alanine. Binding of cluster I antibodies was inhibited by the anti-functional
      anti-beta1 antibody Mab13, and binding of Gi9 and JA218 to alpha2beta1 was
      inhibited by substituting Mn(2+) for Mg(2+), demonstrating that these antibodies
      were sensitive to changes initiated outside the vWFA domain. Mapping of epitopes
      showed that JA202 and Gi9 bound between residues 212-216, while JA208 bound
      between residues 199-216. We have therefore identified two epitope clusters with
      novel properties; i.e. they are intimately associated with the collagen-binding
      site, responsive to conformational changes at the collagen-binding site and
      sensitive to events initiated outside the vWFA domain.

PMID- 10947966
TI  - Transcription of genes encoding pregnancy-specific glycoproteins is regulated by
      negative promoter-selective elements.
AB  - The human pregnancy-specific glycoprotein (PSG) genes comprise a family of 11
      highly conserved members whose expression is maximal in placental cells and
      marginal in other cell types. We have investigated here the molecular basis of
      PSG regulation by analysing a large regulatory region of the PSG-5 gene in cells
      that do and do not express these genes. The promoter region (-254 to -43), which
      does not contain a TATA-box, large GC-rich sequences or a classical initiator,
      was active in all cell types analysed. Additional upstream sequences up to
      position -3204 repressed promoter activity. Two independent repressor regions
      were identified and found to operate effectively in HeLa, COS-7 and HTR8/SVneo
      placental cells. More significantly, these negatively acting modules failed to
      repress a heterologous TATA-containing thymidine kinase promoter. Detailed
      transcriptional and DNA-protein analyses of the proximal repressor region (-605
      to -254) revealed the presence of both negative and positive cis-acting elements.
      Disruption of the repressive functions resulted in an enhanced transcription of
      the reporter constructs. In conclusion, these results demonstrate that PSG-5 gene
      transcription is highly repressed by promoter-selective negative regulatory
      regions and the relief of repression allows enhanced PSG-5 gene transcription
      irrespective of the cell type. Furthermore, our findings suggest that PSG genes
      are expressed mainly through a derepression mechanism.

PMID- 10947967
TI  - Kinetic and stereochemical studies on novel inactivators of C-terminal amidation.
AB  - C-terminal amidation, a required post-translational modification for the
      bioactivation of many neuropeptides, entails sequential enzymic action by
      peptidylglycine alpha-mono-oxygenase (PAM, EC 1.14.17.3) and
      peptidylamidoglycolate lyase (PGL, EC 4.3.2.5). Here we introduce novel compounds
      in which an olefinic functionality is incorporated into peptide analogues as the
      most potent turnover-dependent inactivators of PAM. Kinetic parameters for PAM
      inactivation by 4-oxo-5-acetamido-6-phenyl-hex-2-enoic acid and 4-oxo-5-acetamido
      6-(2-thienyl)-hex-2-enoic acid were obtained by using both the conventional
      dilution assay method and the more complex progress curve method. The results
      obtained from the progress curve method establish that these compounds exhibit
      the kinetic characteristics of pure competitive inactivators (i.e. no ESI complex
      forms during inactivation). On the basis of k(inact)/K(i) values, 4-oxo-5
      acetamido-6-(2-thienyl)-hex-2-enoic acid is almost two orders of magnitude more
      potent than benzoylacrylate, a chemically analogous olefinic inactivator that
      lacks the peptide moiety. Stereochemical studies established that PAM
      inactivation by 4-oxo-5-acetamido-6-(2-thienyl)-hex-2-enoic acid is
      stereospecific with respect to the moiety at the P(2) position, which is
      consistent with previous results with substrates and reversible inhibitors. In
      contrast, 2, 4-dioxo-5-acetamido-6-phenylhexanoic acid, which is a competitive
      inhibitor with respect to ascorbate, exhibits a low degree of stereospecificity
      in binding to the ascorbate sites of both PAM and dopamine-beta-hydroxylase.

PMID- 10947968
TI  - Multidrug resistance protein 1 regulates lipid asymmetry in erythrocyte
      membranes.
AB  - The role of multidrug resistance protein 1 (MRP1) in the maintenance of
      transbilayer lipid asymmetry in the erythrocyte membrane was investigated. The
      transbilayer distribution of endogenous phospholipids and [(7-nitrobenz-2-oxa-1,3
      diazol-4-yl)amino]hexanoyl (NBD)-labelled lipid analogues was compared in the
      absence and the presence of inhibitors of MRP1. At equilibrium the transbilayer
      distribution of the NBD analogues (in the absence of MRP1 inhibitors) was very
      similar to that of the endogenous lipids. Inhibition of MRP1 by verapamil or
      indomethacin resulted in a shift in the amount of probe that was internalized:
      approx. 50% of NBD-labelled phosphatidylcholine (PtdCho) and 9% of NBD
      sphingomyelin (NBD-Spm) were no longer extractable by BSA in cells treated with
      inhibitor, in comparison with 25% and 3% for control cells respectively. To
      verify whether inhibition of MRP1 also affected the distribution of the
      endogenous phospholipids, phospholipase A2 and sphingomyelinase were used to
      assess the amount of each of the various lipid classes present in the membrane
      outer leaflet. No shift in phospholipid distribution was observed after 5 h of
      incubation with verapamil or indomethacin. However, after 48 h of incubation with
      these inhibitors, significantly smaller amounts of PtdCho and Spm were present in
      the outer membrane leaflet. No appreciable change was observed in the
      distribution of phosphatidylethanolamine or phosphatidylserine. Decreased
      hydrolysis of PtdCho and Spm was not due to endovesicle formation, as revealed by
      electron microscopy. This is the first report to show that MRP1 has a role in the
      maintenance of the outwards orientation of endogenous choline-containing
      phospholipids in the erythrocyte membrane.

PMID- 10947969
TI  - Identification of copper ligands in Aspergillus oryzae tyrosinase by site
      directed mutagenesis.
AB  - Copper ligands of the recombinant tyrosinase from the fungus Aspergillus oryzae
      expressed in Saccharomyces cerevisiae or Escherichia coli were identified by site
      directed mutagenesis. The recombinant protyrosinases expressed in S. cerevisiae
      were assayed for catalytic activities of mono-oxygenase and L-dopa oxidase at pH
      5.5 after acid shock at pH 3.0. Replacements of His-63, His-84, His-93, His-290,
      His-294, His-332 or His-333 with asparagine resulted in mutant enzymes exhibiting
      no activities. The site-directed mutant Cys82Ala showed that Cys-82 was also an
      essential residue for the activity. We obtained homogeneous preparations of
      activated tyrosinases from mutated thioredoxin fusion gene products expressed in
      E. coli by acid shock. The copper contents of engineered mutants and wild-type
      enzyme expressed in E. coli were determined by atomic absorption
      spectrophotometry. The wild-type enzyme contained 2 g-atoms of copper/mol of the
      subunit. The His63Asn, His84Asn, His93Asn, His290Asn, His294Asn, His332Asn,
      His333Asn or Cys82Ala substitution decreased copper binding by approx. 50%,
      indicating that the mutants contain only approx. 1 g-atom of copper/mol of the
      subunit. The five mutants His63Asn, His93Asn, His290Asn, His294Asn and Cys82Ala
      contain only one copper ion, which is fully detectable by EPR. From the
      correlation of g( parallel) and (Cu)A( parallel), we deduced that the nitrogen or
      sulphur donors in the copper ligands should be in a square or a distorted
      tetrahedral geometric environment. In further atomic absorption spectrophotometry
      experiments, no copper atom was observed in the seven double mutants
      His63Asn/His290Asn, His63Asn/His294Asn, His63Asn/His332Asn, His63Asn/His333Asn,
      Cys82Ala/His290Asn, His84Asn/His333Asn and His93Asn/His290Asn. We propose a new
      structure of active sites of tyrosinase from A. oryzae: the most likely binding
      sites of tyrosinase for Cu(A) are His-63, His-84 and His-93, with the remaining
      conserved Cys-82 providing the fourth ligand. Cu(B) liganded by four histidine
      residues, His-290, His-294, His-332 and His-333, is identified as new binding
      motif of Cu(B).

PMID- 10947970
TI  - Differential effects of endurance training and creatine depletion on regional
      mitochondrial adaptations in rat skeletal muscle.
AB  - To examine the combined effects of 2-week endurance training and 3-week feeding
      with beta-guanidinopropionic acid (GPA) on regional adaptability of skeletal
      muscle mitochondria, intermyofibrillar mitochondria (IFM) and subsarcolemmal
      mitochondria (SSM) were isolated from quadriceps muscles of sedentary control,
      trained control, sedentary GPA-fed and trained GPA-fed rats. Mitochondrial
      oxidative phosphorylation was assessed polarographically by using pyruvate plus
      malate, succinate (plus rotenone), and ascorbate plus N,N,N',N'-tetramethyl-p
      phenylenediamine (TMPD) (plus antimycin) as respiratory substrates. Assays of
      cytochrome c oxidase and F(1)-ATPase activities were also performed. In sedentary
      control rats, IFM exhibited a higher oxidative capacity than SSM, whereas F(1)
      ATPase activities were similar. Training increased the oxidative phosphorylation
      capacity of mitochondria with both pyruvate plus malate and ascorbate plus TMPD
      as substrates, with no differences between IFM and SSM. In contrast, the GPA diet
      mainly improved the overall SSM oxidative phosphorylation capacity, irrespective
      of the substrate used. Finally, the superimposition of training to feeding with
      GPA strongly increased both oxidase and enzymic activities in SSM, whereas no
      cumulative effects were found in IFM mitochondria. It therefore seems that
      endurance training and feeding with GPA, which are both known to alter the
      energetic status of the muscle cell, might mediate distinct biochemical
      adaptations in regional skeletal muscle mitochondria.

PMID- 10947972
TI  - Internally quenched fluorescent peptide substrates disclose the subsite
      preferences of human caspases 1, 3, 6, 7 and 8.
AB  - Subsite interactions are considered to define the stringent specificity of
      proteases for their natural substrates. To probe this issue in the proteolytic
      pathways leading to apoptosis we have examined the P(4), P(1) and P(1)' subsite
      preferences of human caspases 1, 3, 6, 7 and 8, using internally quenched
      fluorescent peptide substrates containing o-aminobenzoyl (also known as
      anthranilic acid) and 3-nitro-tyrosine. Previous work has demonstrated the
      importance of the S(4) subsite in directing specificity within the caspase
      family. Here we demonstrate the influence of the S(1) and S(1)' subsites that
      flank the scissile peptide bond. The S(1) subsite, the major specificity
      determining site of the caspases, demonstrates tremendous selectivity, with a
      20000-fold preference for cleaving substrates containing aspartic acid over
      glutamic acid at this position. Thus caspases are among the most selective of
      known endopeptidases. We find that the caspases show an unexpected degree of
      discrimination in the P(1)' position, with a general preference for small amino
      acid residues such as alanine, glycine and serine, with glycine being the
      preferred substituent. Large aromatic residues are also surprisingly well
      tolerated, but charged residues are prohibited. While this describes the general
      order of P(1)' subsite preferences within the caspase family, there are some
      differences in individual profiles, with caspase-3 being particularly
      promiscuous. Overall, the subsite preferences can be used to predict natural
      substrates, but in certain cases the cleavage site within a presumed natural
      substrate cannot be predicted by looking for the preferred peptide cleavage
      sites. In the latter case we conclude that second-site interactions may overcome
      otherwise sub-optimal cleavage sequences.

PMID- 10947973
TI  - NMR structural determination of viscotoxin A3 from Viscum album L.
AB  - The high-resolution three-dimensional structure of the plant toxin viscotoxin A3,
      from Viscum album L., has been determined in solution by (1)H NMR spectroscopy at
      pH 3.6 and 12 degrees C (the structure has been deposited in the Protein Data
      Bank under the id. code 1ED0). Experimentally derived restraints including 734
      interproton distances from nuclear Overhauser effect measurements, 22 hydrogen
      bonds, 32 &phi; angle restraints from J coupling measurements, together with
      three disulphide bridge constraints were used as input in restrained molecular
      dynamics, followed by minimization, using DYANA and Discover. Backbone and heavy
      atom root-mean-square deviations were 0.47+/-0.11 A (1 A=10(-10) m) and 0.85+/
      0.13 A respectively. Viscotoxin A3 consists of two alpha-helices connected by a
      turn and a short stretch of antiparallel beta-sheet. This fold is similar to that
      found in other thionins, such as crambin, hordothionin-alpha and -beta,
      phoratoxin A and purothionin-alpha and -beta. The difference in the observed
      biological activity for thionins of known structure is discussed in terms of the
      differences in the calculated surface potential distribution, playing an
      important role in their function through disruption of cell membranes. In
      addition, the possible role in DNA binding of the helix-turn-helix motif of
      viscotoxin A3 is discussed.

PMID- 10947971
TI  - Multidrug resistance protein MRP1 protects against the toxicity of the major
      lipid peroxidation product 4-hydroxynonenal.
AB  - 4-Hydroxynonenal (4HNE) is the most prevalent toxic lipid peroxidation product
      formed during oxidative stress. It exerts its cytotoxicity mainly by the
      modification of intracellular proteins. The detection of 4HNE-modified proteins
      in several degenerative disorders suggests a role for 4HNE in the onset of these
      diseases. Efficient protection mechanisms are required to prevent the
      intracellular accumulation of 4HNE. The toxicity of 4HNE was tested with the
      small cell lung cancer cell lines GLC(4) and the multidrug-resistance-protein
      (MRP1)-overexpressing counterpart GLC(4)/Adr. In the presence of the MRP1
      inhibitor MK571 or the GSH-depleting agent buthionine sulphoximine, both cell
      lines became more sensitive and showed decreased survival. Transport experiments
      were performed with the (3)H-labelled glutathione S-conjugate of 4HNE ([(3)H]GS
      4HNE) with membrane vesicles from GLC(4)-derived cell lines with different
      expression levels of MRP1. [(3)H]GS-4HNE was taken up in an ATP-dependent manner
      and the transport rate was dependent on the amount of MRP1. The MRP1 inhibitor
      MK571 decreased [(3)H]GS-4HNE uptake. MRP1-specific [(3)H]GS-4HNE transport was
      demonstrated with membrane vesicles from High Five insect cells overexpressing
      recombinant MRP1. Kinetic experiments showed an apparent K(m) of 1.6+/-0.21
      microM (mean+/-S.D.) for MRP1-mediated [(3)H]GS-4HNE transport. In conclusion,
      MRP1 has a role in the protection against 4HNE toxicity and GS-4HNE is a novel
      MRP1 substrate. MRP1, together with GSH, is hypothesized to have a role in the
      defence against oxidative stress.

PMID- 10947974
TI  - A role for serine-175 in modulating the molecular conformation of calponin.
AB  - Calponin is an actin filament-associated protein found in smooth muscle and non
      muscle cells. Calponin inhibits actin-myosin interaction in a manner that is
      prevented by protein kinase C (PKC)-catalysed phosphorylation of serine-175. To
      investigate the molecular basis of serine-175-mediated regulation, we examined
      the effect of phosphorylation on the conformation of calponin using monoclonal
      antibody (mAb) epitope analysis. Eight mAbs against different epitopes on chicken
      gizzard calponin were developed to monitor the conformational changes in calponin
      induced by PKC-mediated phosphorylation or serine-175-->alanine (S175A)
      substitution. The relative affinities of the mAbs for calponins immobilized on
      microtitre plates or bound to actin-tropomyosin thin filaments were determined,
      and epitope competitions between free and immobilized calponins were carried out.
      The changes in binding affinity between mAb paratopes and calponin epitopes
      demonstrate several serine-175 modification-induced conformational effects: (a)
      structures of calponin are reconfigured by serine-175 modification, supporting
      the regulatory function of serine-175; (b) there are submolecular structures
      unaffected by modification of serine-175 in both free and thin filament
      associated calponins, suggesting that the serine-175-based conformational
      modulation is a targeted allosteric effect; (c) significant conformational
      changes are detected between free and thin filament-associated calponins,
      indicating two functional states of the molecular conformation; and (d) the
      different epitope characteristics between thin filament-bound and free calponins
      suggest that calponin is a flexible molecule, and the modifications of serine-175
      may also determine the structural flexibility to increase the epitope
      accessibility. These results provide novel information concerning the structure
      function relationships of calponin and its regulation by phosphorylation.

PMID- 10947975
TI  - Fetuin-B, a second member of the fetuin family in mammals.
AB  - A set of orthologous plasma proteins found in human, sheep, pig, cow and rodents,
      now collectively designated fetuin-A, constitutes the fetuin family. Fetuin-A has
      been identified as a major protein during fetal life and is also involved in
      important functions such as inhibition of the insulin receptor tyrosine kinase
      activity, protease inhibitory activities and development-associated regulation of
      calcium metabolism and osteogenesis. Furthermore, fetuin-A is a key partner in
      the recovery phase of an acute inflammatory response. We now describe a second
      protein of the fetuin family, called fetuin-B, which is found at least in human
      and rodents. On grounds of domain homology, overall conservation of cysteine
      residues and chromosomal assignments of the corresponding genes in these species,
      fetuin-B is unambiguously a paralogue of fetuin-A. Yet, fetuin-A and fetuin-B
      exhibit significant differences at the amino acid sequence level, notably
      including variations with respect to the archetypal fetuin-specific signature.
      Differences and similarities in terms of gene regulation were also observed.
      Indeed, studies performed during development in rat and mouse showed for the
      first time high expression of a member of the fetuin family in adulthood, as
      shown with the fetuin-B mRNA in rat. However, like its fetuin-A counterpart, the
      fetuin-B mRNA level is down-regulated during the acute phase of experimentally
      induced inflammation in rat.

PMID- 10947976
TI  - Characterization of rat liver malonyl-CoA decarboxylase and the study of its role
      in regulating fatty acid metabolism.
AB  - In the liver, malonyl-CoA is central to many cellular processes, including both
      fatty acid biosynthesis and oxidation. Malonyl-CoA decarboxylase (MCD) is
      involved in the control of cellular malonyl-CoA levels, and functions to
      decarboxylate malonyl-CoA to acetyl-CoA. MCD may play an essential role in
      regulating energy utilization in the liver by regulating malonyl-CoA levels in
      response to various nutritional or pathological states. The purpose of the
      present study was to investigate the role of liver MCD in the regulation of fatty
      acid oxidation in situations where lipid metabolism is altered. A single MCD
      enzyme of molecular mass 50.7 kDa was purified from rat liver using a sequential
      column chromatography procedure and the cDNA was subsequently cloned and
      sequenced. The liver MCD cDNA was identical to rat pancreatic beta-cell MCD cDNA,
      and contained two potential translational start sites, producing proteins of 50.7
      kDa and 54.7 kDa. Western blot analysis using polyclonal antibodies generated
      against rat liver MCD showed that the 50.7 kDa isoform of MCD is most abundant in
      heart and liver, and of relatively low abundance in skeletal muscle (despite
      elevated MCD transcript levels in skeletal muscle). Tissue distribution
      experiments demonstrated that the pancreas is the only rat tissue so far
      identified that contains both the 50.7 kDa and 54. 7 kDa isoforms of MCD. In
      addition, transfection of the full-length rat liver MCD cDNA into COS cells
      produced two isoforms of MCD. This indicated either that both initiating
      methionines are functionally active, generating two proteins, or that the 54.7
      kDa isoform is the only MCD protein translated and removal of the putative
      mitochondrial targeting pre-sequence generates a protein of approx. 50.7 kDa in
      size. To address this, we transiently transfected a mutated MCD expression
      plasmid (second ATG to GCG) into COS-7 cells and performed Western blot analysis
      using our anti-MCD antibody. Western blot analysis revealed that two isoforms of
      MCD were still present, demonstrating that the second ATG may not be responsible
      for translation of the 50.7 kDa isoform of MCD. These data also suggest that the
      smaller isoform of MCD may originate from intracellular processing. To ascertain
      the functional role of the 50. 7 kDa isoform of rat liver MCD, we measured liver
      MCD activity and expression in rats subjected to conditions which are known to
      alter fatty acid metabolism. The activity of MCD was significantly elevated under
      conditions in which hepatic fatty acid oxidation is known to increase, such as
      streptozotocin-induced diabetes or following a 48 h fast. A 2-fold increase in
      expression was observed in the streptozotocin-diabetic rats compared with control
      rats. In addition, MCD activity was shown to be enhanced by alkaline phosphatase
      treatment, suggesting phosphorylation-related control of the enzyme. Taken
      together, our data demonstrate that rat liver expresses a 50.7 kDa form of MCD
      which does not originate from the second methionine of the cDNA sequence. This
      MCD is regulated by at least two mechanisms (only one of which is
      phosphorylation), and its activity and expression are increased under conditions
      where fatty acid oxidation increases.

PMID- 10947978
TI  - Formation, stability, and breakup of nanojets
AB  - Atomistic molecular dynamics simulations reveal the formation of nanojets with
      velocities up to 400 meters per second, created by pressurized injection of fluid
      propane through nanoscale convergent gold nozzles with heating or coating of the
      nozzle exterior surface to prevent formation of thick blocking films. The
      atomistic description is related to continuum hydrodynamic modeling through the
      derivation of a stochastic lubrication equation that includes thermally triggered
      fluctuations whose influence on the dynamical evolution increases as the jet
      dimensions become smaller. Emergence of double-cone neck shapes is predicted when
      the jet approaches nanoscale molecular dimensions, deviating from the long-thread
      universal similarity solution obtained in the absence of such fluctuations.

PMID- 10947977
TI  - Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear
      orphan receptor TR3.
AB  - TR3, an immediate-early response gene and an orphan member of the steroid-thyroid
      hormone-retinoid receptor superfamily of transcription factors, regulates
      apoptosis through an unknown mechanism. In response to apoptotic stimuli, TR3
      translocates from the nucleus to mitochondria to induce cytochrome c release and
      apoptosis. Mitochondrial targeting of TR3, but not its DNA binding and
      transactivation, is essential for its proapoptotic effect. Our results reveal a
      mechanism by which a nuclear transcription factor translocates to mitochondria to
      initiate apoptosis.

PMID- 10947979
TI  - Forming electrical networks in three dimensions by self-assembly
AB  - Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder
      dots, wires, and light-emitting diodes, generated electrically functional, three
      dimensional networks. The patterns of dots and wires controlled the structure of
      the networks formed; both parallel and serial connections were generated.

PMID- 10947980
TI  - A
AB  - A solid state, electronically addressable, bistable [2]catenane-based molecular
      switching device was fabricated from a single monolayer of the [2]catenane,
      anchored with phospholipid counterions, and sandwiched between an n-type
      polycrystalline silicon bottom electrode and a metallic top electrode. The device
      exhibits hysteretic (bistable) current/voltage characteristics. The switch is
      opened at +2 volts, closed at -2 volts, and read at approximately 0.1 volt and
      may be recycled many times under ambient conditions. A mechanochemical mechanism
      for the action of the switch is presented and shown to be consistent with
      temperature-dependent measurements of the device operation.

PMID- 10947982
TI  - Earthquake potential along the northern hayward fault, california
AB  - The Hayward fault slips in large earthquakes and by aseismic creep observed along
      its surface trace. Dislocation models of the surface deformation adjacent to the
      Hayward fault measured with the global positioning system and interferometric
      synthetic aperture radar favor creep at approximately 7 millimeters per year to
      the bottom of the seismogenic zone along a approximately 20-kilometer-long
      northern fault segment. Microearthquakes with the same waveform repeatedly occur
      at 4- to 10-kilometer depths and indicate deep creep at 5 to 7 millimeters per
      year. The difference between current creep rates and the long-term slip rate of
      approximately 10 millimeters per year can be reconciled in a mechanical model of
      a freely slipping northern Hayward fault adjacent to the locked 1868 earthquake
      rupture, which broke the southern 40 to 50 kilometers of the fault. The potential
      for a major independent earthquake of the northern Hayward fault might be less
      than previously thought.

PMID- 10947981
TI  - Isotopic evidence for variations in the marine calcium cycle over the Cenozoic.
AB  - Significant variations in the isotopic composition of marine calcium have
      occurred over the last 80 million years. These variations reflect deviations in
      the balance between inputs of calcium to the ocean from weathering and outputs
      due to carbonate sedimentation, processes that are important in controlling the
      concentration of carbon dioxide in the atmosphere and, hence, global climate. The
      calcium isotopic ratio of paleo-seawater is an indicator of past changes in
      atmospheric carbon dioxide when coupled with determinations of paleo-pH.

PMID- 10947983
TI  - Remobilization in the cratonic lithosphere recorded in polycrystalline diamond
AB  - Polycrystalline diamonds (framesites) from the Venetia kimberlite in South Africa
      contain silicate minerals whose isotopic and trace element characteristics
      document remobilization of older carbon and silicate components to form the
      framesites shortly before kimberlite eruption. Chemical variations within the
      garnets correlate with carbon isotopes in the diamonds, indicating
      contemporaneous formation. Trace element, radiogenic, and stable isotope
      variations can be explained by the interaction of eclogites with a carbonatitic
      melt, derived by remobilization of material that had been stored for a
      considerable time in the lithosphere. These results indicate more recent
      formation of diamonds from older materials within the cratonic lithosphere.

PMID- 10947984
TI  - Degradation of outer membrane protein A in Escherichia coli killing by neutrophil
      elastase.
AB  - In determining the mechanism of neutrophil elastase (NE)-mediated killing of
      Escherichia coli, we found that NE degraded outer membrane protein A (OmpA),
      localized on the surface of Gram-negative bacteria. NE killed wild-type, but not
      OmpA-deficient, E. coli. Also, whereas NE-deficient mice had impaired survival in
      response to E. coli sepsis, as compared to wild-type mice, the presence or
      absence of NE had no influence on survival in response to sepsis that had been
      induced with OmpA-deficient E. coli. These findings define a mechanism of
      nonoxidative bacterial killing by NE and point to OmpA as a bacterial target in
      host defense.

PMID- 10947985
TI  - Pig cloning by microinjection of fetal fibroblast nuclei.
AB  - Pig cloning will have a marked impact on the optimization of meat production and
      xenotransplantation. To clone pigs from differentiated cells, we microinjected
      the nuclei of porcine (Sus scrofa) fetal fibroblasts into enucleated oocytes, and
      development was induced by electroactivation. The transfer of 110 cloned embryos
      to four surrogate mothers produced an apparently normal female piglet. The clonal
      provenance of the piglet was indicated by her coat color and confirmed by DNA
      microsatellite analysis.

PMID- 10947986
TI  - Twists in catalysis: alternating conformations of Escherichia coli thioredoxin
      reductase.
AB  - In thioredoxin reductase (TrxR) from Escherichia coli, cycles of reduction and
      reoxidation of the flavin adenine dinucleotide (FAD) cofactor depend on rate
      limiting rearrangements of the FAD and NADPH (reduced form of nicotinamide
      adenine dinucleotide phosphate) domains. We describe the structure of the flavin
      reducing conformation of E. coli TrxR at a resolution of 3.0 angstroms. The
      orientation of the two domains permits reduction of FAD by NADPH and oxidation of
      the enzyme dithiol by the protein substrate, thioredoxin. The alternate
      conformation, described by Kuriyan and co-workers, permits internal transfer of
      reducing equivalents from reduced FAD to the active-site disulfide. Comparison of
      these structures demonstrates that switching between the two conformations
      involves a "ball-and-socket" motion in which the pyridine nucleotide-binding
      domain rotates by 67 degrees.

PMID- 10947987
TI  - Asef, a link between the tumor suppressor APC and G-protein signaling.
AB  - The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous
      polyposis and in sporadic colorectal tumors. Here the APC gene product is shown
      to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide
      exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse
      colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF
      activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling,
      and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef
      complex may regulate the actin cytoskeletal network, cell morphology and
      migration, and neuronal function.

PMID- 10947988
TI  - Genes expressed in human tumor endothelium.
AB  - To gain a molecular understanding of tumor angiogenesis, we compared gene
      expression patterns of endothelial cells derived from blood vessels of normal and
      malignant colorectal tissues. Of over 170 transcripts predominantly expressed in
      the endothelium, 79 were differentially expressed, including 46 that were
      specifically elevated in tumor-associated endothelium. Several of these genes
      encode extracellular matrix proteins, but most are of unknown function. Most of
      these tumor endothelial markers were expressed in a wide range of tumor types, as
      well as in normal vessels associated with wound healing and corpus luteum
      formation. These studies demonstrate that tumor and normal endothelium are
      distinct at the molecular level, a finding that may have significant implications
      for the development of anti-angiogenic therapies.

PMID- 10947989
TI  - Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant
      protein-3.
AB  - Tissue degradation by the matrix metalloproteinase gelatinase A is pivotal to
      inflammation and metastases. Recognizing the catalytic importance of substrate
      binding exosites outside the catalytic domain, we screened for extracellular
      substrates using the gelatinase A hemopexin domain as bait in the yeast two
      hybrid system. Monocyte chemoattractant protein-3 (MCP-3) was identified as a
      physiological substrate of gelatinase A. Cleaved MCP-3 binds to CC-chemokine
      receptors-1, -2, and -3, but no longer induces calcium fluxes or promotes
      chemotaxis, and instead acts as a general chemokine antagonist that dampens
      inflammation. This suggests that matrix metalloproteinases are both effectors and
      regulators of the inflammatory response.

PMID- 10947990
TI  - Modulation of human visual cortex by crossmodal spatial attention.
AB  - A sudden touch on one hand can improve vision near that hand, revealing
      crossmodal links in spatial attention. It is often assumed that such links
      involve only multimodal neural structures, but unimodal brain areas may also be
      affected. We tested the effect of simultaneous visuo-tactile stimulation on the
      activity of the human visual cortex. Tactile stimulation enhanced activity in the
      visual cortex, but only when it was on the same side as a visual target. Analysis
      of effective connectivity between brain areas suggests that touch influences
      unimodal visual cortex via back-projections from multimodal parietal areas. This
      provides a neural explanation for crossmodal links in spatial attention.

PMID- 10947991
TI  - Stomatal patterning in angiosperms.
AB  - My thesis is that understanding stomatal patterning requires a holistic
      perspective. Since stomata are structures critical to the survival of terrestrial
      plants, they need to be viewed in relation to their function and their interface
      with other structural components. With this outlook, I begin by discussing
      pattern types, means of measuring them, advantages of each type of measurement,
      and then present patterning from evolutionary, physiological, ecological, and
      organ views. I suggest areas where I believe profitable studies might enable us
      to better understand stomatal patterning. The final sections of the paper review
      stomatal patterning on angiosperm leaves and present a theory of patterning. With
      the abundance of molecular information, and coming genomic sequences and new
      tools, an opportunity exists to dissect the process of how cells are selected to
      become different from their neighbors and assume a fate critical to plant
      survival. Understanding this biological process at the molecular level requires
      comprehending the broad base on which stomatal patterning rests.

PMID- 10947992
TI  - Fate of oxygen losses from Typha domingensis (Typhaceae) and Cladium jamaicense
      (Cyperaceae) and consequences for root metabolism.
AB  - The objective of this work was to determine whether radial oxygen loss (ROL) from
      roots of Typha domingensis and Cladium jamaicense creates an internal oxygen
      deficiency or, conversely, indicates adequate internal aeration and leakage of
      excess oxygen to the rhizosphere. Methylene blue in agar was used to visualize
      the pattern of ROL from roots, and oxidation of a titanium-citrate solution was
      used to quantify rates of oxygen leakage. Typha's roots had a higher porosity
      than Cladium's and responded to flooding treatment by increasing cortical air
      space, particularly near the root tips. A greater oxygen release, which occurred
      along the subapical root axis, and an increase in rhizosphere redox potential
      (E(h)) over time were associated with the well-developed aerenchyma system in
      Typha. Typha roots, regardless of oxygen release pattern, showed low or
      undetectable alcohol dehydrogenase (ADH) activity or ethanol concentrations,
      indicating that ROL did not cause internal deficiencies. Cladium roots also
      released oxygen, but this loss primarily occurred at the root tips and was
      accompanied by increased root ADH activity and ethanol concentrations. These
      results support the hypothesis that oxygen release by Cladium is accompanied by
      internal deficiencies of oxygen sufficient to stimulate alcoholic fermentation
      and helps explain Cladium's lesser flood tolerance in comparison with Typha.

PMID- 10947993
TI  - Differential siring success of Pgi genotypes in Clarkia Unguiculata (Onagraceae).
AB  - Competition among pollen grains for the fertilization of ovules can play an
      important role in determining the male and female reproductive success of
      flowering plants. To examine the influence of pollen-donor genotype on male
      reproductive success, hand-pollinations were conducted on Clarkia unguiculata and
      the siring success of pollen-donor plants was compared between donors homozygous
      for different allelomorphs of the allozyme PGI (phosphoglucoisomerase). Donors
      homozygous for the B allele sired more seeds than C-allele donors. Single-donor
      crosses indicated that C-donor-sired seeds are aborted more often than are B
      donor-sired seeds, suggesting that the B-allele donor's advantage in mixed
      pollinations was a result of differential abortion. A negative relationship
      between pollen load and the siring success of B-allele donors implies that pollen
      from B-allele donors has reduced performance relative to C-allele donors when
      pollen loads are high. These data demonstrate consistent differences in siring
      success between individuals homozygous for different alleles at a single locus
      and suggest that variation at the Pgi locus may be maintained by a post
      pollination trade-off.

PMID- 10947994
TI  - Growth and invasive potential of Sapium sebiferum (Euphorbiaceae) within the
      coastal prairie region: the effects of soil and moisture regime.
AB  - The introduced tree Sapium sebiferum (Euphorbiaceae) is considered a serious
      threat to the preservation of the coastal prairie region of Louisiana and Texas,
      although it is currently uncommon in the western part of the region. The
      objective of this study was to evaluate the potential effects of location, soils,
      and available moisture on the growth and survival of S. sebiferum in coastal
      prairie. In a field experiment, S. sebiferum mortality was significantly greater
      at a western site than at central and eastern sites. The greatest mortality and
      least growth of surviving plants occurred on a soil from the western region,
      regardless of site. A greenhouse study also found that S. sebiferum growth was
      lowest on the western soil. Watering frequency significantly affected S.
      sebiferum growth, except on the western soil. Sapium sebiferum growth responded
      to both nitrogen and phosphorus additions for all soils. Soil analyses revealed
      the highest sand, sodium, and phosphorus contents, and much higher electrical
      conductivity in the western soil. It is concluded that the soil examined from the
      western region is unfavorable for S. sebiferum growth, though not to the extent
      to preclude S. sebiferum completely. Evidence suggests that soil salinity may be
      the primary cause of the poor S. sebiferum growth at the western site.

PMID- 10947995
TI  - Theoretical aspects of surface-to-volume ratios and water-storage capacities of
      succulent shoots.
AB  - Surface-to-volume (S/V) ratios of drought-adapted plants affect transpiration,
      photosynthesis, and water-storage capacity. The S/V ratio of cladodes and flat
      leaves is S/V = 2/T, where T is thickness: even slight thickening greatly reduces
      S/V. During rain/drought cycles succulent stems swell and shrink without tearing
      by having flexible ribs, but ribs increase S/V above that of a smooth cylindrical
      stem with equal volume: the increased surface area is S(ribbed)/S(cylindrical) =
      N[x + (pi/N)]/pi(1 + x), where N is number of ribs and x is rib height relative
      to the radius of the inner stem. Numerous low ribs provide moderate expandability
      (storage volume) with little increase in S/V and are adaptive where droughts are
      short. Tall ribs provide greater expandability but greatly increase S/V and
      probably are adaptive only in mesic habitats. Having ~8-15 ribs, each about as
      tall as the inner stem radius, provides large storage capacity and intermediate
      increase in S/V. By increasing absolute size, S/V is reduced so greatly that even
      large ribs can have an S/V smaller than that of a narrow cylindrical or spherical
      stem with less volume.

PMID- 10947996
TI  - Cortical development in roots of the aquatic plant Pontederia cordata
      (Pontederiaceae).
AB  - Adventitious roots of marsh-grown Pontederia cordata were examined to determine
      cortical development and structure. The innermost layer of the ground meristem
      forms the endodermis and aerenchymatous cortex. The outermost layer of the early
      ground meristem undergoes a precise pattern of oblique and periclinal cell
      divisions to produce a single or double layer of prohypodermis with an anchor
      cell for each radial file of aerenchyma cells. At maturity, endodermal cell walls
      are modified only by narrow Casparian bands. The central regions of the ground
      meristem become proaerenchyma and exhibit asymmetric cell division and expansion.
      They produce an aerenchymatous zone with barrel-shaped large cells and
      irregularly shaped small cells traversing the aerenchyma horizontally along
      radii; some crystalliferous cells with raphides are present in the aerenchyma.
      The walls of the hypodermis are modified early by polyphenols. The outermost
      layer of the hypodermis later matures into an exodermis with Casparian bands that
      are impermeable to berberine, an apoplastic tracer dye. The nonexodermal layer(s)
      of the hypodermis has suberin-modified walls. Radial files of aerenchyma are
      usually connected by narrow protuberances near their midpoints, the aerenchyma
      lacunae having been produced by expansion of cells along walls lining
      intercellular spaces. We are terming this type of aerenchyma development, which
      is neither schizogenous nor lysigenous, "differential expansion."

PMID- 10947997
TI  - RAPD variation among and within small and large populations of the rare clonal
      plant Ranunculus reptans (Ranunculaceae).
AB  - In the pre-alpine region of Europe numbers and sizes of populations of the clonal
      lake shore plant Ranunculus reptans have declined because of the regulation of
      lake water levels. We investigated genetic variation among and within 17
      populations of different size (cover 1-10 000 m) in R. reptans with RAPD (random
      amplified polymorphic DNA) profiles. We sampled 127 rosettes in 14 populations at
      Lake Constance and three populations at or near Lake Como. There was significant
      genetic variation between plants from the two lake regions (5.9%, analysis of
      molecular variance [AMOVA], P < 0.001), among populations within lake regions
      (20.4%, P < 0.001), and within populations (73.7%, P < 0.001). Under the
      assumptions of Wright's island model the variation among populations corresponds
      to a gene flow of N(e)m = 0.70. Within the 14 Lake Constance populations we
      detected significant genetic variation among subpopulations separated by only a
      few metres (4.0% of the within-population variation; P < 0.05). Molecular
      variance was 24% smaller in small populations covering <100 m area than in larger
      ones (P < 0.03), indicating that samples from large populations were genetically
      more variable than samples representing comparable areas of smaller populations.
      We conclude that gene flow among populations is very limited and that genetic
      drift has caused reduced genetic variability of smaller populations. Conservation
      of genetic variability in R. reptans requires persistence of large and also of
      small populations (because of population differentiation), and it could be
      enhanced by increasing the size of small populations (to counter genetic drift).

PMID- 10947998
TI  - Genetic diversity and population structure of the serpentine endemic Calystegia
      collina (Convolvulaceae) in northern California.
AB  - We used enzyme electrophoresis to evaluate genetic diversity in 32 populations of
      Calystegia collina, a clonal plant species endemic to serpentine outcrops in
      northern California (USA). Of 34 loci examined 56% were polymorphic, but on
      average only 17% were polymorphic within local populations. Neither the total
      number of alleles nor the number of multilocus genotypes differed significantly
      between populations in small vs. large serpentine outcrops. Genetic and
      geographic distances between populations were positively correlated, but this
      relationship was not significantly affected by the isolation of serpentine
      outcrops. Populations were highly differentiated (F(st) = 0.417) and little
      genetic variation was explained by geographic region or serpentine
      outcrop.Observed heterozygosity within populations almost always exceeded Hardy
      Weinberg expectations. In many populations, all 30 sample ramets were uniformly
      heterozygous at one or more loci yet were genetically variable at other loci.
      These results imply that many C. collina populations originate from one or a few
      genetic founders, with little recruitment from seeds. Genetic variation within
      uniformly heterozygous populations must be the product of multiple, closely
      related founders or somatic mutations within the population. We conclude that
      vegetative reproduction, perhaps coupled with somatic mutation, helps maintain
      genetic diversity in these isolated but long-lived populations.

PMID- 10948000
TI  - Routes of origin of two recently evolved hybrid taxa: Senecio vulgaris var.
      hibernicus and York radiate groundsel (Asteraceae).
AB  - The possible pathways of origin of two recently arisen introgressant forms of
      Senecio vulgaris (i.e., var. hibernicus and York radiate groundsel) were
      investigated in experimental crosses between tetraploid S. vulgaris var. vulgaris
      and the normally diploid S. squalidus. Comparison of the morphology of
      synthesized hybrid progeny with established taxa, by discriminant function
      analysis, revealed that fertile hybrid offspring similar in morphology to S.
      vulgaris var. hibernicus and York radiate groundsel could be synthesized: (1)
      following formation of genomically stable diploid gametes by the triploid hybrid;
      (2) through the production of unreduced gametes by diploid S. squalidus; and (3)
      when a tetraploid form of S. squalidus acted as one of the parents. It was
      evident that hybrid offspring similar in morphology to the two introgressant taxa
      were more often produced in backcrosses to S. vulgaris than in segregating F2 or
      F3 generations (53% as opposed to 36%), and that fertile hybrid progeny were
      formed within two generations. Because hybridization between S. vulgaris and S.
      squalidus occurs regularly, although at very low frequency, in natural mixed
      populations in the British Isles, there is the potential for multiple origins to
      occur in the wild of both S. vulgaris var. hibernicus and York radiate groundsel.

PMID- 10947999
TI  - Population genetics of two rare perennials in isolated wetlands: Sagittaria
      isoetiformis and S. teres (Alismataceae).
AB  - We investigated genetic structure in two closely related perennial plants that
      occur in isolated wetlands: Sagittaria isoetiformis, restricted to the
      southeastern Coastal Plain of North America, and S. teres, endemic to the
      northeastern Coastal Plain. Using horizontal starch-gel electrophoresis, we
      screened 527 individuals from 11 populations of S. isoetiformis and 367
      individuals from seven populations of S. teres. A high proportion of the 16 loci
      were polymorphic (%P(S) = 93.8% in S. isoetiformis and %P(S) = 75.0% in S.
      teres), with higher mean numbers of alleles per polymorphic locus and effective
      alleles per locus in S. isoetiformis (AP = 3.27, A(E) = 1.90) than in S. teres
      (AP = 2.58, A(E) = 1.30). Species- and population-level expected heterozygosities
      were higher in S. isoetiformis (H(ES) = 0.399, H(EP) = 0.218) than in S. teres
      (H(ES) = 0.177, H(EP) = 0.101). Jackknife estimates of F statistics indicated
      moderate levels of inbreeding in S. teres (F(IS) = 23.1%). Strong differentiation
      characterized these geographically isolated populations (G(ST) = 39.9% in S.
      isoetiformis, and G(ST) = 26.1% in S. teres). Genetic identities varied
      substantially within (I = 75%, range = 0.558-0.963 in S. isoetiformis; I = 89%,
      range = 0.776-0.963 in S. teres) and among species (I = 81%, range = 0.506
      0.882), leading to the discrimination of four regional population clusters using
      nonmetric multidimensional scaling (NMDS). It appears that S. isoetiformis and S.
      teres are a progenitor-derivative species pair.

PMID- 10948001
TI  - Evidence for natural selection in a fern hybrid zone.
AB  - Morphological characters, chloroplast DNA, and allozymes were used to analyze the
      distribution of individuals within a hybrid population of the ferns Polystichum
      munitum and P. imbricans in northwestern California. Microsites within the
      population were characterized according to soil moisture and light levels
      reaching the plants. In sites with low soil moisture and high light levels, all
      of the ferns were genetically and morphologically like P. imbricans. In contrast,
      ferns with the genetic and morphological identity of P. munitum predominated in
      moist shady sites. Intermediate sites supported very few P.munitum, a wide
      variety of hybrid recombinants, and a majority of ferns with P. imbricans
      characteristics. The pattern of variation within the population is noteworthy
      because of the close proximity of the habitat extremes and the long-range
      dispersal of fern spores. We conclude that natural selection along environmental
      gradients must be a major factor in determining the ecological and genetic
      associations within the hybrid zone. The results of this study are evaluated in
      the context of the fern life cycle and compared to the assumptions of models
      explaining the establishment and maintenance of hybrid zones, which vary in the
      role attributed to environmentally mediated natural selection.

PMID- 10948002
TI  - Population-specific gender-biased hybridization between Dryopteris intermedia and
      D. carthusiana: evidence from chloroplast DNA.
AB  - As has been shown for many kinds of organisms, barriers to interspecific
      hybridization may differ in strength between reciprocal crosses, resulting in a
      bias in the probability that one or the other species may be the maternal or
      paternal parent of hybrids. The fern Dryopteris Xtriploidea, the "backcross"
      hybrid between the diploid D. intermedia and the tetraploid D. carthusiana,
      occurs in large numbers in nature, providing an opportunity to investigate
      whether such a bias exists. Differences in the chloroplast genome distinguishing
      the two parental species were discovered in the sequence of the trnL region
      following amplification by polymerase chain reaction (PCR), including a Mse I
      restriction site. This allowed rapid identification of the donor of the
      chloroplast genome, and therefore the maternal parent of each hybrid, assuming
      chloroplast DNA to be maternally inherited in Dryopteris. Analysis was carried
      out on 127 hybrids, shown to be of independent origin using allozymes, occurring
      at three localities in Virginia and West Virginia. When samples from all
      localities were pooled, 91 possessed the D. carthusiana trnL genotype and 36
      possessed the D. intermedia genotype, a ratio that is significantly different (P
      < 0.001) from the null hypothesis of no gender bias. The strength of the bias
      differed significantly among the three sites, however, with bias at the West
      Virginia site much stronger (5.6:1 carthusiana:intermedia; P < 0.001) than at
      either Virginia site (1.55:1 and 1.43:1 carthusiana:intermedia, respectively; P >
      0.05 in both cases). The cause of the strong bias in the West Virginia sample is
      unknown, as is the cause of the population differences. Causes of bias could
      include differences between the parental species related to their ploidy
      difference, including sizes of gametes and/or gametangia, sperm motility,
      breeding system (D. intermedia is outcrossing while D. carthusiana is selfing),
      or the nature and strength of interspecific isolating mechanisms.

PMID- 10948003
TI  - Bird-pollination of three Durio species (Bombacaceae) in a tropical rainforest in
      Sarawak, Malaysia.
AB  - Pollination ecology of three Durio species, D. grandiflorus, D. oblongus, and D.
      kutejensis (Bombacaceae), was studied in a lowland dipterocarp forest in Sarawak,
      Malaysia, during a peak flowering period when at least 305 species of plants
      bloomed in 1996. Durio has been reported to be pollinated by bats in Peninsular
      Malaysia. However, my observations of flower visitors and pollination experiments
      indicated that two species, D. grandiflorus and D. oblongus, were pollinated by
      spiderhunters (Nectariniidae) and that the other species, D. kutejensis, was
      pollinated by giant honey bees and bats as well as birds. Hand-pollination
      experiments showed that all three species were obligate outbreeders. A resource
      limitation in fruit production was suggested. The former two species were visited
      only by spiderhunters, and the bagged flowers that were opened for animal
      visitors only at night bore no fruit, while those that were opened only during
      the day bore fruits, at comparable fruiting ratios to open pollination. Durio
      kutejensis was observed to be visited by giant honey bees, birds, and bats at
      different times of day, and three series of bagged experiments that exposed the
      flowers to animal visitors at different times of day bore fruits at a comparable
      ratio to open-pollination.

PMID- 10948004
TI  - Occurrence of plastids in rye (Poaceae) sperm cells.
AB  - Studies using classic genetics as well as restriction fragment length
      polymorphism analysis have demonstrated that rye, unlike most flowering plants,
      has biparental inheritance of both plastids and mitochondria. Yet, a previous in
      depth ultrastructural study found no plastids in rye sperm cells, and DNA
      specific staining revealed no cytoplasmic DNA in the male gametes of this plant.
      In the present study, we examined serial ultrathin sections of eight rye sperm
      cells (four pairs) and found unambiguous examples of plastids in all cases. The
      number of plastids per sperm cell varies from two to 12. The sperm of a pair may
      vary with regard to plastid number; however, these differences are not consistent
      among the sperm pairs examined.

PMID- 10948005
TI  - Two male-sterile mutants of Zea Mays (Poaceae) with an extra cell division in the
      anther wall.
AB  - Two recessive male-sterile mutants of maize with similar patterns of pollen
      abortion were studied. Genetic studies showed that one of the two mutations was
      allelic with a previously identified male-sterility locus (ms23) and the other
      mutation was in a newly identified male-sterility locus (ms32). Cytological
      characterization of homozygous mutants and fertile heterozygous control siblings
      was performed using brightfield, fluorescence, and electron microscopy. During
      normal anther development, the final anther wall periclinal division divides the
      secondary parietal anther wall layer into the middle layer and tapetum, forming
      an anther with four wall layers. This is followed by differentiation of the
      tapetal cells into protoplastic binucleate, secretory tissue. In both the ms23
      and ms32 mutants, the prospective tapetal layer divided into two layers, termed
      t1 and t2, forming an anther with five wall layers. Neither the t1 nor the t2
      layers differentiated normally into tapetal layers, as determined by examination
      of cell walls, nucleus number, and cytoplasmic organization. Pollen mother cells
      aborted after the onset of prophase I of meiosis, suggesting that an early
      developmental coordination may exist between tapetum and pollen mother cells.

PMID- 10948006
TI  - Phytochemistry and the systematics and ecology of Loasaceae and Gronoviaceae
      (Loasales).
AB  - A screening for iridoid compounds of 78 of 315 species from all major groups in
      Gronoviaceae and Loasaceae has been carried out. The results were compared to the
      systematic concepts in the family and distribution and ecology of the taxa.
      Iridoids are present in at least some species of all genera screened. Some
      simple, monomeric compounds (e.g., loganin, sweroside) are found in all major
      groups of the two families and represent the basic iridoid inventory. Other
      compounds are restricted to certain taxonomic groups: nine-carbon iridoids (e.g.,
      deutzioside) are restricted to Mentzelia (Loasaceae subfam. Mentzelioideae),
      hetero-oligomeric iridoids (e.g., tricoloroside methyl ester, acerifolioside) are
      restricted to two small groups in Loasa (Loasa ser. Macrospermae and ser.
      Floribundae, Loasaceae subfam. Loasoideae), and oleosides (e.g., 10
      hydroxyoleoside dimethyl ester) are restricted to the large genus Caiophora sensu
      Weigend). The distribution of certain iridoid compounds thus confirms some of the
      generic limits. Iridoid phytochemistry does not correlate with systematic
      entities above the generic level nor does it in any way correlate with the
      morphological evolution of taxa. Conversely, the amount and complexity of iridoid
      compounds present in taxa correlate positively with the aridity of their habitat
      and the extent of mammalian herbivore pressure.

PMID- 10948007
TI  - Climate and the U.S. distribution of C4 grass subfamilies and decarboxylation
      variants of C4 photosynthesis.
AB  - I compared the C(4) grass flora and climatic records for 32 sites in the United
      States. Consistent with previous studies, I found that the proportion of the
      grass flora that uses the NADP malic enzyme (NADP-ME) variant of C(4)
      photosynthesis greatly increases with increasing annual precipitation, while the
      proportion using the NAD malic enzyme (NAD-ME) variant (and also the less common
      phosphoenolpyruvate carboxykinase [PCK] variant) decreases. However the
      association of grass subfamilies with annual precipitation was even stronger than
      for the C(4) decarboxylation variants. Analysis of the patterns of distribution
      by partial correlation analysis showed that the correlations between the
      frequency of various C(4) types and rainfall were solely due to the association
      of the C(4) types with particular grass subfamilies. In contrast, there was a
      strong correlation of the frequency of the different subfamilies with annual
      precipitation that was independent of the influence of the different C(4)
      variants. It therefore appears that other, as yet unidentified, characteristics
      that differ among grass subfamilies may be responsible for their differences in
      distribution across natural precipitation gradients.

PMID- 10948008
TI  - Never underestimate the force of reproduction.

PMID- 10948009
TI  - Telling children about a parent's cancer.

PMID- 10948010
TI  - Gastro-oesophageal cancer: death at the junction.

PMID- 10948011
TI  - New system for GP recruitment.

PMID- 10948013
TI  - The BMJ christmas revue. Send Us your sketches

PMID- 10948012
TI  - Information technology and telemedicine in sub-saharan Africa.

PMID- 10948014
TI  - Premature babies have high death and disability rate

PMID- 10948015
TI  - Breastfeeding programmes "should be targeted"

PMID- 10948016
TI  - "Hands-free" mobile phones may be safer than the rest.

PMID- 10948018
TI  - In brief

PMID- 10948017
TI  - Death keeps Irish doctors guessing.

PMID- 10948020
TI  - Persistence of tuberculosis explained

PMID- 10948019
TI  - Israelis and Palestinians collaborate over health care.

PMID- 10948021
TI  - Risk of vCJD lower than expected

PMID- 10948022
TI  - One million threatened by suspension of Sudan's relief lifeline.

PMID- 10948023
TI  - French men invited to become "vasectomy tourists".

PMID- 10948024
TI  - Toys can turn hospital cots into "reservoirs of bacteria"

PMID- 10948025
TI  - Randomised controlled trial of homoeopathy versus placebo in perennial allergic
      rhinitis with overview of four trial series.
AB  - OBJECTIVE: To test the hypothesis that homoeopathy is a placebo by examining its
      effect in patients with allergic rhinitis and so contest the evidence from three
      previous trials in this series. DESIGN: Randomised, double blind, placebo
      controlled, parallel group, multicentre study. SETTING: Four general practices
      and a hospital ear, nose, and throat outpatient department. PARTICIPANTS: 51
      patients with perennial allergic rhinitis. INTERVENTION: Random assignment to an
      oral 30c homoeopathic preparation of principal inhalant allergen or to placebo.
      MAIN OUTCOME MEASURES: Changes from baseline in nasal inspiratory peak flow and
      symptom visual analogue scale score over third and fourth weeks after
      randomisation. RESULTS: Fifty patients completed the study. The homoeopathy group
      had a significant objective improvement in nasal airflow compared with the
      placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1,
      P=0.0001). Both groups reported improvement in symptoms, with patients taking
      homoeopathy reporting more improvement in all but one of the centres, which had
      more patients with aggravations. On average no significant difference between the
      groups was seen on visual analogue scale scores. Initial aggravations of rhinitis
      symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%),
      P=0.04). Addition of these results to those of three previous trials (n=253)
      showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for
      homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to
      15.4, P=0.0007). CONCLUSION: The objective results reinforce earlier evidence
      that homoeopathic dilutions differ from placebo.

PMID- 10948026
TI  - Effect of 1995 pill scare on rates of venous thromboembolism among women taking
      combined oral contraceptives: analysis of general practice research database.
AB  - OBJECTIVE: To compare the incidence of venous thromboembolism among women taking
      combined oral contraceptives before and after the October 1995 pill scare.
      DESIGN: Analysis of General Practice Research Database. SETTING: United Kingdom,
      January 1993 to December 1998. SUBJECTS: Women aged 15-49 taking combined oral
      contraceptives. MAIN OUTCOME MEASURES: Incidence of venous thromboembolism.
      RESULTS: Use of so called "third generation" combined oral contraceptives fell
      from 53% during January 1993 to October 1995 to 14% during November 1995 to
      December 1998. There was no significant change in the incidence of venous
      thromboembolism between the two periods after age was adjusted for (incidence
      ratio 1.04, 95% confidence interval 0.78 to 1.39). CONCLUSIONS: The findings are
      not compatible with the assertion that third generation oral contraceptives are
      associated with a twofold increase in risk of venous thromboembolism compared
      with older progestogens.

PMID- 10948027
TI  - Qualitative interview study of communication between parents and children about
      maternal breast cancer.
AB  - OBJECTIVE: To examine parents' communication with their children about the
      diagnosis and initial treatment of breast cancer in the mother. DESIGN:
      Qualitative interview study within cross sectional cohort. SETTING: Two breast
      cancer treatment centres. PARTICIPANTS: 32 women with stage I or stage II breast
      cancer with a total of 56 school aged children. MAIN OUTCOME MEASURES:
      Semistructured interview regarding timing and extent of communication with
      children about the diagnosis and initial treatment of the mother's illness,
      reasons for talking to children or withholding information, and help available
      and requested from health professionals. RESULTS: Women were most likely to begin
      talking to their children after their diagnosis had been confirmed by biopsy, but
      a minority waited until after surgery or said nothing at all. Family discussion
      did not necessarily include mention of cancer. There was considerable consistency
      in the reasons given for either discussing or not discussing the diagnosis. The
      most common reason for not communicating was avoidance of children's questions
      and particularly those about death. While most mothers experienced helpful
      discussion with a doctor concerning their illness, few were offered help with
      talking to children; many would have liked help, particularly the opportunity for
      both parents to talk to a health professional with experience in understanding
      and talking to children. CONCLUSIONS: Parents diagnosed with cancer or other
      serious illnesses should be offered help to think about whether, what, and how to
      tell their children and about what children can understand, especially as they
      may well be struggling themselves to come to terms with their illness.

PMID- 10948028
TI  - Time trends in schizophrenia mortality in Stockholm county, Sweden: cohort study.

PMID- 10948029
TI  - Rapid diagnosis of Falciparum malaria by using the ParaSight F test in travellers
      returning to the United Kingdom: prospective study.

PMID- 10948030
TI  - Homage to delirium

PMID- 10948032
TI  - Artie Shaw's philosophy on life

PMID- 10948034
TI  - Looking at the evidence

PMID- 10948031
TI  - Consultation patterns and provision of contraception in general practice before
      teenage pregnancy: case-control study.
AB  - OBJECTIVES: To determine patterns of consultation in general practice and
      provision of contraception before teenage pregnancy. DESIGN: Case-control study,
      with retrospective analysis of case notes. SETTING: 14 general practices in Trent
      region. SUBJECTS: 240 registered patients (cases) with a recorded conception
      before the age of 20. Three controls per case were matched by age and practice.
      MAIN OUTCOME MEASURES: Consultations in general practice and provision of
      contraception in the 12 months before conception and recorded provision of
      contraception at any time before conception. RESULTS: Overall, 223 cases (93%)
      had consulted a health professional at least once in the year before conception,
      171 (71%) had discussed contraception in this time, and 121 (50%) had been
      prescribed oral contraception. Cases were more likely to have consulted in the
      year before conception than controls (odds ratio 2. 70, 95% confidence interval
      1.56 to 4.66). Most of the difference was owing to consultation for
      contraception. Overall, 53 cases (22%) resulted in a termination of pregnancy.
      Cases whose pregnancy ended in a termination were more likely to have received
      emergency contraception than either their controls (3.21, 1.32 to 7.79) or cases
      resulting in other outcomes (3.01, 1.06 to 8.51). CONCLUSIONS: Most teenagers who
      became pregnant attended general practice in the year before pregnancy, and many
      had sought contraceptive advice. The reluctance of teenagers to attend general
      practice for contraception may be less than previously supposed. The association
      between provision of emergency contraception and pregnancy ending in termination
      emphasises the need for continuing follow up of teenagers consulting for this
      form of contraception.

PMID- 10948033
TI  - Drug treatment of multiple sclerosis.

PMID- 10948036
TI  - Hindu teeth

PMID- 10948035
TI  - ABC of oral health. Oral health care for patients with special needs.

PMID- 10948037
TI  - UK management guidelines for erectile dysfunction.

PMID- 10948038
TI  - Statistics notes: blinding in clinical trials and other studies.

PMID- 10948039
TI  - Reducing error, improving safety. Defensive culture of British medicine needs to
      change.

PMID- 10948040
TI  - Reducing error, improving safety. Log of errors is needed.

PMID- 10948041
TI  - Reducing error, improving safety. Relation between reported mishaps and safety is
      unclear.

PMID- 10948042
TI  - Reducing error, improving safety. No fault compensation protects patients in
      Nordic countries.

PMID- 10948043
TI  - Reducing error, improving safety. Doctors could certainly take lessons from
      aviation.

PMID- 10948044
TI  - Reducing error, improving safety. "Do all things practicable to reduce risk"
      should apply in health system.

PMID- 10948045
TI  - Reducing error, improving safety. Health professionals should take responsibility
      for gross carelessness.

PMID- 10948046
TI  - Reducing error, improving safety. Blaming individuals is more emotionally
      satisfying than targeting institutions.

PMID- 10948048
TI  - Powerful forces at work

PMID- 10948047
TI  - Reducing error, improving safety. Medical errors must be discussed during medical
      education.

PMID- 10948049
TI  - Reducing error, improving safety. Safety of systems can often be improved.

PMID- 10948050
TI  - Reducing error, improving safety. Systems approach to intrapartum risk management
      is important.

PMID- 10948051
TI  - Reducing error, improving safety. Crew resource management training should be
      mandatory in anaesthesia.

PMID- 10948052
TI  - Reducing error, improving safety. Anaesthesia is different from anaesthesiology.

PMID- 10948053
TI  - Reducing error, improving safety. Technology cannot replace healthcare workers.

PMID- 10948054
TI  - Crisis in the air. Account is misleading and condescending.

PMID- 10948055
TI  - Crisis in the air. Automated defibrillators are safer than levitating dentists or
      horizontal internists.

PMID- 10948056
TI  - Circulation research Editors' yearly report: 1999-2000

PMID- 10948057
TI  - Local delivery of ceramide for restenosis: is there a future for lipid therapy?

PMID- 10948058
TI  - Rho, tyrosine kinase, Ca(2+), and junctions in endothelial hyperpermeability.

PMID- 10948059
TI  - Cardiac gap junction remodeling by stretch: is it a good thing?

PMID- 10948060
TI  - Calcium fluxes involved in control of cardiac myocyte contraction.

PMID- 10948062
TI  - Endotoxemia in transgenic mice overexpressing human glutathione peroxidases.
AB  - In response to endotoxemia induced by administration of lipopolysaccharide, a
      complex series of reactions occurs in mammalian tissues. During this inflammation
      response, cells produce different mediators, such as reactive oxygen species, a
      number of arachidonic acid metabolites, and cytokines. The reactive oxygen
      species thus generated have been suggested to produce tissue injury as a result
      of macromolecular damage or by interfering with regulatory processes. They may
      also act as important signaling molecules to induce redox-sensitive genes. We
      report here that transgenic mice overexpressing 2 major forms of human
      glutathione peroxidases (GPs), intra- and extracellular GP, are able to modulate
      host response during endotoxemic conditions. We show that these animals have a
      decreased hypotension and increased survival rate after administration of a high
      dosage of lipopolysaccharide. Overexpression of GPs alters vascular permeability
      and production of cytokines (interleukin-1 beta and tumor necrosis factor-alpha)
      and NO, affects arachidonic acid metabolism, and inhibits leukocyte migration.
      These results suggest an important role for peroxides in pathogenesis during
      endotoxemia, and GPs, by regulating their level, may prove to be good candidates
      for antioxidant therapy to protect against such injury.

PMID- 10948061
TI  - Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch
      injury in carotid arteries.
AB  - Neointimal hyperplasia at the site of surgical intervention is a common and
      deleterious complication of surgery for cardiovascular diseases. We hypothesized
      that direct delivery of a cell-permeable growth-arresting lipid via the balloon
      tip of an embolectomy catheter would limit neointimal hyperplasia after stretch
      injury. We have previously demonstrated that sphingolipid-derived ceramide
      arrested the growth of smooth muscle cell pericytes in vitro. Here, we show that
      ceramide-coated balloon catheters significantly reduced neointimal hyperplasia
      induced by balloon angioplasty in rabbit carotid arteries in vivo. This ceramide
      treatment decreased the number of vascular smooth muscle cells entering the cell
      cycle without inducing apoptosis. In situ autoradiographic studies demonstrated
      that inflating the balloon catheter forced cell-permeable ceramide into the
      intimal and medial layers of the artery. Intercalation of ceramide into vascular
      smooth muscle cells correlated with rapid inhibition of trauma-associated
      phosphorylation of extracellular signal-regulated kinase and protein kinase B.
      These studies demonstrate the utility of cell-permeable ceramide as a novel
      therapy for reducing neointimal hyperplasia after balloon angioplasty.

PMID- 10948063
TI  - In vivo analysis of an essential myosin light chain mutation linked to familial
      hypertrophic cardiomyopathy.
AB  - Mutations in cardiac motor protein genes are associated with familial
      hypertrophic cardiomyopathy. Mutations in both the regulatory (Glu22Lys) and
      essential light chains (Met149Val) result in an unusual pattern of hypertrophy,
      leading to obstruction of the midventricular cavity. When a human genomic
      fragment containing the Met149Val essential myosin light chain was used to
      generate transgenic mice, the phenotype was recapitulated. To unambiguously
      establish a causal relationship for the regulatory and essential light chain
      mutations in hypertrophic cardiomyopathy, we generated mice that expressed either
      the wild-type or mutated forms, using cDNA clones encompassing only the coding
      regions of the gene loci. Expression of the proteins did not lead to a
      hypertrophic response, even in senescent animals. Changes did occur at the
      myofilament and cellular levels, with the myofibrils showing increased Ca(2+)
      sensitivity and significant deficits in relaxation in a transgene dose-dependent
      manner. Clearly, mice do not always recapitulate important aspects of human
      hypertrophy. However, because of the discordance of these data with data obtained
      in transgenic mice containing the human genomic fragment, we believe that the
      concept that these point mutations by themselves can cause hypertrophic
      cardiomyopathy should be revisited.

PMID- 10948064
TI  - Protein tyrosine kinase is not involved in the infarct size-limiting effect of
      ischemic preconditioning in canine hearts.
AB  - Protein kinase C (PKC) plays an important role in ischemic preconditioning (IP).
      Because (1) tyrosine kinase is located at the downstream of PKC for IP in the
      rabbit hearts and (2) we have reported that ecto-5'-nucleotidase is the substrate
      for PKC and plays a crucial role for the infarct size-limiting effect, we tested
      whether tyrosine kinase activation contributes to either activation of ecto-5'
      nucleotidase or the infarct size-limiting effect of the early phase of IP in the
      canine heart. In dogs, the IP procedure (4 cycles of 5-minute occlusion of
      coronary artery) and exposure to 12, 13-phorbol myristate acetate (PMA) each
      activated myocardial ecto-5'-nucleotidase and Lck tyrosine kinase. Genistein (10,
      30, and 100 microg. kg(-)(1). min(-)(1) IC), an inhibitor of tyrosine kinase,
      attenuated the activation of Lck tyrosine kinase but did not attenuate the
      activation of ecto-5'-nucleotidase due to either IP or PMA. In the other canine
      hearts, IP attenuated infarct size (49+/-5 versus 11+/-3 or 16+/-3%, P<0.01) due
      to 90 minutes of coronary occlusion followed by 6 hours of reperfusion, which was
      not blunted by 3 or 2 (30 and 100 microg. kg(-)(1). min(-)(1)) doses of genistein
      (infarct sizes, 15+/-4, 13+/-4, and 13+/-3%, respectively, and 17+/-3 and 15+/
      4%, respectively) or lavendustin A. Tyrosine kinase does not activate ecto-5'
      nucleotidase or trigger the infarct size-limiting effect of the early phase of IP
      in canine hearts.

PMID- 10948065
TI  - Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of
      protein kinase C.
AB  - The present study is designed to test whether phosphatidylinositol 3-kinase (PI3
      kinase) has a role in the signaling pathway in ischemic preconditioning (PC) and
      whether it is proximal or distal to protein kinase C (PKC). Before 20 minutes of
      global ischemia, Langendorff-perfused rat hearts were perfused for 20 minutes
      (control); preconditioned with 4 cycles of 5-minute ischemia and 5-minute reflow
      (PC); treated with either wortmannin (WM) or LY 294002 (LY), each of which is a
      PI3-kinase inhibitor, for 5 minutes before and throughout PC; treated with 1,2
      dioctanoyl-sn-glycerol (DOG), an activator of PKC for 10 minutes (DOG); treated
      identically to the DOG group except with WM added 10 minutes before and during
      perfusion with DOG; or treated with either WM or LY for 25 minutes. Recovery of
      left ventricular developed pressure (LVDP; percentage of initial preischemic
      LVDP), measured after 30 minutes of reflow, was improved by PC (72+/-2% versus
      36+/-4% in control; P<0.001), and this was blocked by WM and LY (41+/-4% and 43+/
      5%, respectively; P<0.05 compared with PC). DOG addition improved postischemic
      LVDP (67+/-6%; P<0.001 compared with control), but in contrast to its effect on
      PC, WM did not completely eliminate the protective effect of DOG (52+/-4%; P>0.05
      compared with DOG; P<0.05 compared with control). PC induced phosphorylation of
      protein kinase B and translocation of PKC epsilon, and it increased NO
      production, and these effects were blocked by WM, which suggests a role for PI3
      kinase in PC upstream of PKC and NO.

PMID- 10948066
TI  - Pulsatile stretch remodels cell-to-cell communication in cultured myocytes.
AB  - Mechanical stretch is thought to play an important role in remodeling atrial and
      ventricular myocardium and may produce substrates that promote arrhythmogenesis.
      In the present work, neonatal rat ventricular myocytes were cultured for 4 days
      as confluent monolayers on thin silicone membranes and then subjected to linear
      pulsatile stretch for up to 6 hours. Action potential upstrokes and propagation
      velocity (theta) were measured with multisite optical recording of transmembrane
      voltage of the cells stained with the voltage-sensitive dye RH237. Expression of
      the gap junction protein connexin43 (Cx43) and the fascia adherens junction
      protein N-cadherin was measured immunohistochemically in the same preparations.
      Pulsatile stretch caused dramatic upregulation of intercellular junction proteins
      after only 1 hour and a further increase after 6 hours (Cx43 signal increased
      from 0.73 to 1.86 and 2.02% cell area, and N-cadherin signal increased from 1.21
      to 2.11 and 2.74% cell area after 1 and 6 hours, respectively). This was
      paralleled by an increase in theta from 27 to 35 cm/s after 1 hour and 37 cm/s
      after 6 hours. No significant change in the upstroke velocity of the action
      potential or cell size was observed. Increased theta and protein expression were
      not reversible after 24 hours of relaxation. Nonpulsatile (static) stretch
      produced qualitatively similar but significantly smaller changes than pulsatile
      stretch. Thus, pulsatile linear stretch in vitro causes marked upregulation of
      proteins that form electrical and mechanical junctions, as well as a concomitant
      increase in propagation velocity. These changes may contribute to
      arrhythmogenesis in myocardium exposed to acute stretch.

PMID- 10948067
TI  - Human brain capillary endothelium: 2-arachidonoglycerol (endocannabinoid)
      interacts with endothelin-1.
AB  - In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide
      and endothelin-1 may involve Ca(2+), cytoskeleton, and vasodilator-stimulated
      phosphoprotein changes mediated by the cGMP/cGMP kinase system.(1) Endothelium of
      human brain capillaries or microvessels is used to examine the interplay of
      endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an
      endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates
      that 2-arachidonoyl glycerol counteracts Ca(2+) mobilization and cytoskeleton
      rearrangement induced by endothelin-1. This event is independent of nitric oxide,
      cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1
      receptor, G protein, phosphoinositol signal transduction pathway, and Ca(2+)
      activated K(+) channels. The induced rearrangements of cellular cytoskeleton
      (actin or vimentin) are partly prevented by inhibition of protein kinase C or
      high levels of potassium chloride. The 2-arachidonoyl glycerol-induced
      phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP.
      These findings suggest that 2-arachidonoyl glycerol may contribute to the
      regulation of cerebral capillary and microvascular function.

PMID- 10948068
TI  - Host gene regulation during coxsackievirus B3 infection in mice: assessment by
      microarrays.
AB  - Host genetic responses that characterize enteroviral myocarditis have not yet
      been determined. The injurious and inflammatory process in heart muscle may
      reflect host responses of benefit to the virus and ultimately result in
      congestive heart failure and dilated cardiomyopathy. On the other hand, host
      responses within the myocardium may secure the host against acute or protracted
      damage. To investigate the nature of modified gene expression in comparison with
      normal tissue, mRNA species were assessed in myocardium using cDNA microarray
      technology at days 3, 9, and 30 after infection. Of 7000 clones initially
      screened, 169 known genes had a level of expression significantly different at 1
      or more postinfection time points as compared with baseline. The known regulated
      genes were sorted according to their functional groups and normalized expression
      patterns and, subsequently, interpreted in the context of viremic, inflammatory,
      and healing phases of the myocarditic process.

PMID- 10948069
TI  - Activation of RhoA by thrombin in endothelial hyperpermeability: role of Rho
      kinase and protein tyrosine kinases.
AB  - Endothelial cells (ECs) actively regulate the extravasation of blood
      constituents. On stimulation by vasoactive agents and thrombin, ECs change their
      cytoskeletal architecture and small gaps are formed between neighboring cells.
      These changes partly depend on a rise in [Ca(2+)](i) and activation of the
      Ca(2+)/calmodulin-dependent myosin light chain kinase. In this study, mechanisms
      that contribute to the thrombin-enhanced endothelial permeability were further
      investigated. We provide direct evidence that thrombin induces a rapid and
      transient activation of RhoA in human umbilical vein ECs. Under the same
      conditions, the activity of the related protein Rac was not affected. This was
      accompanied by an increase in myosin light chain phosphorylation, the generation
      of F-actin stress fibers, and a prolonged increase in endothelial permeability.
      Inhibition of the RhoA target Rho kinase with the specific inhibitor Y-27632
      reduced all of these effects markedly. In the presence of Y-27632, the thrombin
      enhanced permeability was additionally reduced by chelation of [Ca(2+)](i) by
      BAPTA. These data indicate that RhoA/Rho kinase and Ca(2+) represent 2 pathways
      that act on endothelial permeability. In addition, the protein tyrosine kinase
      inhibitor genistein reduced thrombin-induced endothelial permeability without
      affecting activation of RhoA by thrombin. Our data support a model of thrombin
      induced endothelial permeability that is regulated by 3 cellular signal
      transduction pathways.

PMID- 10948070
TI  - Blood pressure patterns in normal pregnancy, gestational hypertension, and
      preeclampsia.
AB  - With the aim to describe the daily pattern of blood pressure during the
      trimesters of pregnancy in clinically healthy women as well as in pregnant women
      who developed gestational hypertension or preeclampsia, we analyzed 1494 blood
      pressure series systematically sampled by ambulatory monitoring for 48 hours
      every 4 weeks after the first obstetric visit in 124 women with uncomplicated
      pregnancies, 55 with gestational hypertension, and 23 with a final diagnosis of
      preeclampsia. The circadian pattern of blood pressure variation for each group
      and trimester of gestation was established by population multiple-component
      analysis. A highly statistically significant circadian pattern represented by a
      linear model that includes components with periods of 24 and 12 hours is
      demonstrated for systolic and diastolic blood pressure for all groups of pregnant
      women in all trimesters (P:<0.001 in all cases). The differences in circadian
      rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly
      statistically significant in all trimesters (always P:<0.001). There is also a
      statistically significant difference in circadian amplitude (extent of daily
      change) of blood pressure between healthy and complicated pregnancies in all
      trimesters (always P:<0.004). Results further indicate similar circadian
      characteristics between women who later developed gestational hypertension or
      preeclampsia in the first trimester of pregnancy. The difference between these 2
      groups in circadian mean is statistically significant in the second trimester for
      systolic (P:=0.022) but not for diastolic blood pressure (P:=0.986). In the third
      trimester, the difference in circadian mean is highly statistically significant
      for both variables (P:<0.001). The differences in blood pressure between healthy
      and complicated pregnancies can be observed as early as in the first trimester of
      pregnancy. Those highly significant differences are found when both systolic and
      diastolic blood pressure for women with a later diagnosis of gestational
      hypertension or preeclampsia are well within the accepted normal physiological
      range of blood pressure variability. These differing changes in the circadian
      pattern of blood pressure with advancing gestational age between healthy and
      complicated pregnancies offer new end points that may lead to an early
      identification of hypertensive complications in pregnancy as well as to the
      establishment of prophylactic intervention.

PMID- 10948071
TI  - Definitive molecular evidence of renin-angiotensin system in human uterine
      decidual cells.
AB  - The tissue renin-angiotensin system (RAS) has been suggested to be present in
      human gestational tissues, but uncertainty exists about the authenticity of this
      RAS, and the cellular origin of this RAS has not been defined. In the present
      study, we confirmed the presence of authentic renin and angiotensinogen in the
      prolactin-producing decidual tissue by sequencing the cDNAs generated through
      reverse transcription-polymerase chain reaction, confirming cDNA product sizes,
      and by performing Northern blot analysis of the RNA. Our comparative data
      demonstrate that prolactin has the highest expression in the decidual tissue,
      followed by renin, and that angiotensinogen has the least expression. We
      demonstrated with fluorescent in situ hybridization that prolactin-expressing
      endocrine decidual cells are the same cells that express both renin and
      angiotensinogen. These results have implications in regard to how the decidual
      RAS may be regulated and what potential role this local RAS may have in the
      pathogenesis of preeclampsia.

PMID- 10948072
TI  - Blood pressure is associated with body mass index in both normal and obese
      children.
AB  - Obesity is associated with elevated blood pressure (BP) both in adults and
      children. Childhood obesity has become a severe health problem, especially during
      the last few decades. So far there has not been any large-scale study
      specifically focusing on the association between obesity and BP in early life.
      The aim of this study is to examine systematically the association between
      obesity and BP in preschool Chinese children in mainland China. In 1996,
      measurements of weight, height, and BP values were collected in a nationwide,
      case-control study of 748 boys and 574 girls who ranged in age from 0.1 to 6.9
      years in 8 cities in mainland China. One obese child and 1 nonobese child were
      matched for gender and age. The BP differences of the mean-matched pair were
      approximately 5 mm Hg for systolic blood pressure (SBP) and approximately 4 mm Hg
      for diastolic blood pressure (DBP) (P<0.05); a higher value was noted in obese
      children. The BP value of 19.4% children in the obese group and 7.0% children in
      the nonobese group was higher than the 95th percentile value (P<0.0001), which is
      defined as high BP by the Task Force on Blood Pressure Control in Children. Both
      SBP and DBP were significantly (P<0.05) positively related to body mass index
      (BMI) values (P<0.05) for children in obese and nonobese groups after adjustment
      for age, gender, and height. To be specific, an increase of 1 BMI unit was
      associated with, on average, an increase of 0.56 mm Hg and 0.54 mm Hg in SBP and
      DBP, respectively, for obese children. In nonobese children, the increase in SBP
      and DBP was 1.22 mm Hg and 1.20 mm Hg, respectively. An increase in the BMI is
      conclusively associated with elevated SBP and DBP in nonobese children.
      Furthermore, an increase in the adjusted BMI was associated with an increase in
      SBP and DBP in obese and nonobese children.

PMID- 10948073
TI  - Effects of exercise and weight loss on mental stress-induced cardiovascular
      responses in individuals with high blood pressure.
AB  - The purpose of this study was to determine the effects of exercise and weight
      loss on cardiovascular responses during mental stress in mildly to moderately
      overweight patients with elevated blood pressure. Ninety-nine men and women with
      high normal or unmedicated stage 1 to stage 2 hypertension (systolic blood
      pressure 130 to 179 mm Hg, diastolic blood pressure 85 to 109 mm Hg) underwent a
      battery of mental stress tests, including simulated public speaking, anger recall
      interview, mirror trace, and cold pressor, before and after a 6-month treatment
      program. Subjects were randomly assigned to 1 of 3 treatments: (1) aerobic
      exercise, (2) weight management combining aerobic exercise with a behavioral
      weight loss program, or (3) waiting list control group. After 6 months, compared
      with control subjects, participants in both active treatment groups had lower
      levels of systolic blood pressure, diastolic blood pressure, total peripheral
      resistance, and heart rate at rest and during mental stress. Compared with
      subjects in the control group, subjects in the exercise and weight management
      groups also had greater resting stroke volume and cardiac output. Diastolic blood
      pressure was lower for the weight management group than for the exercise-only
      group during all mental stress tasks. These results demonstrate that exercise,
      particularly when combined with a weight loss program, can lower both resting and
      stress-induced blood pressure levels and produce a favorable hemodynamic pattern
      resembling that targeted for antihypertensive therapy.

PMID- 10948074
TI  - Modulation of blood pressure and obesity with the dopamine D2 receptor gene TaqI
      polymorphism.
AB  - Pharmacological data suggest that obesity and blood pressure (BP) may be
      modulated through the dopamine D2 receptor (DD2R), which may represent an
      underlying mechanism that links these conditions. A TAQ:I polymorphism near the
      DD2R gene has been associated with indices of obesity in white populations. We
      compared anthropometric and fasting plasma biochemical parameters between 209
      nondiabetic hypertensive and 174 gender-matched normotensive Chinese subjects.
      The hypertensives had increased dyslipidemia, increased fasting plasma glucose
      concentrations, and a greater degree of obesity. The A1 and A2 alleles of the
      DD2R gene TAQ:I polymorphism were identified with a polymerase chain reaction
      based restriction fragment length polymorphism protocol. The A1 allele frequency
      was decreased in the hypertensives (42.0%) compared with the control subjects
      (52.0%, P=0.006), and genotype frequencies were different (P=0.05) between the 2
      groups. In the combined population (n=383), systolic, diastolic, and mean
      arterial BPs were 6, 5, and 6 mm Hg lower, respectively, in subjects with the
      A1A1 genotype relative to the A2A2 genotype (all P<0.05), whereas skinfold
      thickness was increased at the iliac (P<0.001) and triceps (P<0.03) sites but not
      at the biceps or subscapular sites. Furthermore, this DD2R gene polymorphism was
      shown to be a significant independent predictor of diastolic BP and iliac and
      triceps skinfold thicknesses (all P<0.03). These contrasting associations of the
      DD2R TAQ:I polymorphism A1 allele with lower BP but increased markers of
      "gynoidal" or peripheral subcutaneous obesity (iliac and triceps skinfold
      thicknesses) in our Chinese population may provide some insight into the
      underlying relationship between BP and body fat distribution, but the exact
      nature of this link remains to be determined.

PMID- 10948075
TI  - Dopamine D1 receptor gene polymorphism is associated with essential hypertension.
AB  - Dopamine has been shown to influence renal sodium excretion through a direct
      interaction with the dopamine receptor (DR). The dopamine D1 receptor (DRD1) has
      been localized to the proximal tubules and is known to increase sodium excretion
      by inhibiting Na-H exchanger and Na,K-ATPase activity. Defective renal dopamine
      production and/or DR function have been reported in essential hypertension (EH)
      as well as in genetic models of animal hypertension. With a restriction fragment
      length polymorphism of the DRD1 gene, we performed an association study in
      patients with EH. One hundred thirty-one subjects with EH and 136 age-matched
      normotensive (NT) controls were studied. Polymerase chain reaction was used to
      amplify the A-48G polymorphic site in the DRD1 gene, and restriction analysis of
      the polymerase chain reaction product was used to score the A and G alleles. The
      allele frequencies in the EH group and NT group were then compared. The G allele
      was observed more frequently in the EH group than in the NT group, and the allele
      frequencies in the 2 groups differed significantly (chi(2)=6.5, P=0.01). Multiple
      logistic linear regression analysis revealed that the genotype frequencies of
      A/A, A/G, and G/G differed significantly (odds ratio=2.1; 95% CI=1.19 to 3.66)
      between the EH and NT groups. EH patients who possess the G allele had a higher
      diastolic blood pressure than those lacking the G allele (P<0.01). Thus, the
      alleles detected by this restriction fragment length polymorphism in the DRD1
      gene are associated with EH, and they appear to influence the diastolic blood
      pressure of Japanese EH patients.

PMID- 10948077
TI  - Telomere length inversely correlates with pulse pressure and is highly familial.
AB  - There is evidence that telomeres, the ends of chromosomes, serve as clocks that
      pace cellular aging in vitro and in vivo. In industrialized nations, pulse
      pressure rises with age, and it might serve as a phenotype of biological aging of
      the vasculature. We therefore conducted a twin study to investigate the relation
      between telomere length in white blood cells and pulse pressure while
      simultaneously assessing the role of genetic factors in determining telomere
      length. We measured by Southern blot analysis the mean length of the terminal
      restriction fragments (TRF) in white blood cells of 49 twin pairs from the Danish
      Twin Register and assessed the relations of blood pressure parameters with TRF.
      TRF length showed an inverse relation with pulse pressure. Both TRF length and
      pulse pressure were highly familial. We conclude that telomere length, which is
      under genetic control, might play a role in mechanisms that regulate pulse
      pressure, including vascular aging.

PMID- 10948076
TI  - CA-Repeat polymorphism in intron 1 of HSD11B2 : effects on gene expression and
      salt sensitivity.
AB  - Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11beta
      hydroxysteroid dehydrogenase cause apparent mineralocorticoid excess, a form of
      familial hypertension. Because the hypertension associated with AME is of the
      salt-sensitive type, it seemed possible that decreases in 11-HSD2 activity might
      be associated with salt sensitivity. To examine this, Italians with mild
      hypertension underwent a protocol consisting of a rapid intravenous saline
      infusion and subsequent furosemide diuresis. To determine whether there were
      genetic associations between HSD11B2 and salt sensitivity, 198 Italians were
      genotyped for a CA repeat polymorphism (11 alleles) in the first intron.
      Increased differences in mean arterial pressure between the sodium loaded and
      depleted states were correlated with shorter CA repeat length (R=0.214, P=0.
      0025). The effect behaved as a recessive trait. This suggested that decreased
      HSD11B2 expression was associated with shorter CA repeat length. Furthermore,
      activity of renal 11-HSD2 as measured by an increase in the ratio of urinary-free
      cortisol/urinary-free cortisone was lower in 33 salt-sensitive subjects (urinary
      free cortisol/urinary-free cortisone 0.89+/-0.04 [mean+/-SE]) compared with 34
      salt-resistant subjects (0.71+/-0.04, P<0.001). However, when minigenes
      containing either 14 or 23 CA repeats were transfected into rabbit or human
      kidney cortical collecting duct cells, the construct with 14 repeats was instead
      expressed at levels 50% higher than those of the construct with 23 repeats, as
      determined by reverse transcription-polymerase chain reaction. We conclude that
      polymorphisms in HSD11B2 and decreased 11-HSD2 activity are associated with
      sensitivity to sodium loading, but a functional explanation for these
      associations remains to be elucidated.

PMID- 10948079
TI  - Augmented sympathetic response to bradykinin in the diabetic heart before
      autonomic denervation.
AB  - We studied whether diabetes mellitus affects the bradykinin (BK)-induced release
      of norepinephrine (NE) from rat cardiac sympathetic endings in situ. Three groups
      were studied. Group A (n=12) was rendered diabetic with streptozotocin (STZ),
      group B (n=13) received STZ and insulin, and group C (n=14) received citrate
      buffer only. NPH insulin was given to group B from day 7 after STZ. Atria were
      paced (3Hz) with rectangular voltage pulses at mechanical threshold intensity
      (0.15 V/cm). The release of NE was assessed through its effects on contractile
      force in the presence of atropine (1 micromol/L). Intensifying the field
      stimulation above the neural threshold ( approximately 0.4 V/cm) produced a
      graded positive inotropic effect that was due to the release of NE from
      sympathetic nerve endings. The additional effect of 0.1 micromol/L BK on the
      force of contraction was determined at half-maximal neural stimulation (ie, at
      approximately 0.65 V/cm). Then, after washing out BK and lowering the stimulation
      intensity to mechanical threshold, a cumulative dose-response curve for added NE
      was generated, allowing the positive inotropic effects of neural stimulation
      (with or without BK) to be expressed in terms of an equivalent inotropic
      concentration of added NE ([NE(eq)]). Neural stimulation, in the absence of BK,
      gave an [NE(eq)] of 32+/-3 nmol/L in group A, 44+/-6 nmol/L in group B, and 37+/
      6 nmol/L in group C. BK increased [NE(eq)] by a factor of 6.2+/-0.9 in group A,
      4.5+/-0.5 in group B, and 3.7+/-0.3 in group C. This factor was greater in group
      A than in group C but indistinguishable in groups B and C. Atria from normal and
      diabetic rats were incubated in (3)[H]NE for 60 minutes. Excess tracer was
      removed, and atria were stimulated during a series of 1-minute episodes at half
      maximal neural stimulation to cause exocytotic (3)[H]NE release. BK augmented
      (3)[H]NE release in normal (n=4) and in diabetic (n=4) atria. This BK-induced
      increase of (3)[H]NE overflow (expressed as a fraction of tissue (3)[H]NE
      radioactivity) was 4 times greater in diabetic than in normal preparations. The
      response to BK in releasing sympathetic neurotransmitter is augmented in diabetic
      rats, recovering in a manner dependent on insulin.

PMID- 10948078
TI  - Effects of bradykinin on prostaglandin I(2) synthesis in human vascular
      endothelial cells.
AB  - The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis
      in endothelial cells were investigated in association with intracellular Ca(2+)
      kinetics, cytosolic phospholipase A(2) (cPLA(2)) activity, and mRNA expression of
      cPLA(2) and prostaglandin H synthase (PGHS) isoforms. Bradykinin enhanced
      prostacyclin release from endothelial cells time-dependently, but pretreatment
      with EGTA H-7 or HOE 140 inhibited bradykinin-induced prostacyclin release.
      Bradykinin increased both the influx of extracellular Ca(2+) and Ca(2+) release
      from the intracellular Ca(2+) storage sites. These reactions occurred within 5
      minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated
      cPLA(2) to 1.3-fold the control level. The constitutive expressions of mRNA of
      cPLA(2), PGHS-1, and PGHS-2 was 87, 562, and 47 amol/microg RNA, respectively.
      With the stimulation of bradykinin, cPLA(2) mRNA increased to 746 amol/microg RNA
      in 15 minutes, PGHS-1 mRNA increased to 10 608 amol/microg RNA, and PGHS-2 mRNA
      increased to 22 400 amol/microg RNA in 180 minutes. Pretreatment with
      cycloheximide superinduced cPLA(2) and PGHS-2 mRNA expression but almost
      completely inhibited PGHS-1. Pretreatment with EGTA had effects similar to
      pretreatment with cycloheximide in the case of cPLA(2) and PGHS-1 but did not
      affect PGHS-2. These findings suggest that the elevation of cPLA(2) activity
      caused by the increase of intracellular Ca(2+) concentration is important in the
      early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms
      regulating cPLA(2) are different from those regulating PGHS isoforms in
      endothelial cells.

PMID- 10948081
TI  - Repair of coronary arterioles after treatment with perindopril in hypertensive
      heart disease.
AB  - In hypertensive heart disease, no data are available on the repair of coronary
      resistance vessels in patients after long-term ACE inhibitor treatment. Fourteen
      patients with essential hypertension were studied with coronary flow reserve and
      with transvenous endomyocardial biopsy before and after 12 months of
      antihypertensive treatment with perindopril (4 to 8 mg/d, mean 5.9+/-2.3 mg/d).
      Left ventricular muscle mass index decreased by 11% (from 145+/-41 to 128+/-36
      g/m(2), P=0.04). Maximal coronary blood flow was increased by 54% (from 170+/-46
      to 263+/-142 mL. min(-1). 100 g(-1), P=0.001), and minimal coronary vascular
      resistance was diminished by 33% (from 0.67+/-0.21 to 0.45+/-0.19 mm Hg. min. 100
      g. mL(-1), P=0.001); consequently, coronary reserve increased by 67% from 2.1+/
      0.6 to 3. 5+/-1.9 (P=0.001). Structural analysis revealed regression of
      periarteriolar collagen area by 54% (from 558+/-270 to 260+/-173 microm(2),
      P=0.04) and of total interstitial collagen volume density by 22% (from 5.5+/-3.8
      Vv% to 4.3+/-3.2 Vv%, P=0.04), whereas arteriolar wall area was slightly but not
      significantly reduced. Long-term therapy with the ACE inhibitor perindopril
      induces structural repair of coronary arterioles that is mainly characterized by
      the regression of periarteriolar fibrosis and associated with a marked
      improvement in coronary reserve. These findings indicate the beneficial
      reparative effects of ACE inhibition on coronary microcirculation in hypertensive
      heart disease.

PMID- 10948080
TI  - Can serum carnitine levels distinguish hypertrophic cardiomyopathy from
      hypertensive hearts?
AB  - Although echocardiography is a useful diagnostic tool in hypertrophic
      cardiomyopathy (HCM), it is sometimes difficult to differentiate it from
      hypertensive heart disease (HHD): some patients with HCM show symmetrical
      hypertrophy, whereas patients with HHD sometimes show asymmetrical septal
      hypertrophy. We used a radioiodinated long-chain fatty acid tracer to visualize
      the altered myocardial fatty acid metabolism of HCM and HHD. Carnitine is the
      essential substance for the beta-oxidation of long-chain fatty acids. We recently
      reported that serum free carnitine levels in HCM were elevated and that they were
      significantly correlated with the severity of myocardial fatty acid metabolic
      disorder. Therefore, we investigated serum carnitine levels in patients with HCM
      and HHD, which can contribute to the differentiation of each other. We studied 56
      patients with HCM and 20 patients with essential hypertension. Serum free
      carnitine levels were significantly higher in patients with HCM than those with
      HHD (HCM 52.5+/-9.5 nmol/mL, HHD 46.6+/-6.4 nmol/mL, P<0.01), but they showed no
      statistical difference between patients with HHD and normal subjects. Serum
      acylcarnitine levels were significantly lower in patients with HCM than those
      with HHD (HCM 10.1+/-4.0 nmol/mL, HHD 14.5+/-4.9 nmol/mL, P<0.0005), although
      they did not differ between patients with HHD and normal subjects. Scintigraphic
      analyses with a long-chain fatty acid analog revealed that myocardial tracer
      uptake was much reduced in patients with HCM compared with that in patients with
      HHD (quantitative analysis: HCM 2.11+/-0.12, HHD 2.22+/-0.17, P<0.05;
      semiquantitative analysis: HCM 13.6+/-6.3, HHD 2.0+/-1.5, P<0.0001). In
      conclusion, the differences in serum carnitine levels between HCM and HHD reflect
      altered myocardial fatty acid metabolic impairment, and the levels can help to
      distinguish these 2 diseases.

PMID- 10948082
TI  - High triglycerides and low HDL cholesterol and blood pressure and risk of
      ischemic heart disease.
AB  - Treatment of high blood pressure (BP) has not produced the expected reduction in
      risk of ischemic heart disease (IHD). Subjects with high BP often have the
      metabolic syndrome X, an aggregation of abnormalities in glucose and lipid
      metabolism. We tested the hypothesis that the BP level would be less predictive
      of risk of IHD in those with high triglycerides (TG) and low HDL cholesterol (HDL
      C), the characteristic dyslipidemia in the metabolic syndrome than in those
      without. Baseline measurements of fasting lipids, systolic BP (SBP), diastolic BP
      (DBP), and other risk factors were obtained in 2906 men, age 53 to 74 years, free
      of overt cardiovascular disease. High TG/low HDL-C was defined as TG >1.59 mmol/L
      and HDL-C <1.18 mmol/L. Within an 8-year period, 229 men developed IHD. In men
      with high TG/low HDL-C, the incidence of IHD according to SBP (<120, 120 to 140,
      >140 mm Hg) was 12.5%, 12.9%, and 10.0% (P=NS), respectively, and according to
      DBP, the incidence of IHD was (<75, 75 to 90, >90 mm Hg) 13.7%, 10.6%, and 13.7%
      (P=NS), respectively. The corresponding figures for other men were 5.2%, 8. 0%,
      and 9.7% for SBP (P<0.001), and 6.1%, 7.5%, and 9.9% for DBP (P<0.03). In
      conclusion, the BP level did not predict the risk of IHD in those with high
      TG/low HDL-C. This finding may explain the reason lowering BP has not produced
      the expected reduction in IHD.

PMID- 10948083
TI  - Effect of antihypertensive therapy on renal injury in type 2 diabetic rats with
      hypertension.
AB  - In a previous study, we demonstrated that doxazosin (DZN), an alpha(1)-adrenergic
      blocker, prevented proteinuria in streptozotocin diabetic rats. In this study, we
      investigated whether DZN would lower established proteinuria by improving
      glomerular sclerosis in spontaneously hypertensive corpulent rats with type 2
      diabetes mellitus. DZN treatment was compared with treatment with angiotensin
      converting enzyme inhibitor, lisinopril (LIS) alone, and DZN in combination with
      LIS. Combination therapy was used to examine any additive effect of either drug
      alone in the reduction of proteinuria and glomerular sclerosis. Both male and
      female rats age 6 months with established proteinuria were used. The rats were
      allocated randomly to 1 of 4 groups: untreated, DZN treated, LIS treated, or a
      combination of DZN and LIS treatment. Drug treatment was continued for 16 weeks.
      The results show that (1) either drug alone or in combination significantly
      lowered systolic blood pressure; (2) DZN, LIS, or combination therapy reduced
      albuminuria at 16 weeks of treatment from baseline by 38.61+/-5.77%, 30.70+/-4.
      21%, and 42.17+/-4.77% (mean+/-SE), respectively. No difference in albuminuria
      was observed among the 3 groups of rats; (3) the fractional mesangial area, which
      was 20.55+/-3.77% in untreated rats, was significantly reduced to 11.18+/-1.32%
      in DZN-treated rats, with a further reduction to 8.72+/-0.64% in LIS-treated rats
      and to 3.48+/-0.35% in rats treated with DZN+LIS; and (4) DZN but not LIS
      significantly improved plasma glucose levels in spontaneously hypertensive
      corpulent rats (untreated 21.06+/-0.97 mmol/L versus DZN treated 15.81+/-0.93
      mmol/L or DZN+LIS treated 17.38+/-1.10 mmol/L; P<0.025 to 0.005). Thus, the data
      suggest that 16-week treatment with either DZN or LIS improves established
      proteinuria and glomerular sclerosis, but combination therapy is superior to
      either DZN or LIS alone in preventing glomerular sclerosis in type 2 diabetic
      rats with hypertension.

PMID- 10948084
TI  - Effects of angiotensin-converting enzyme inhibitors on glucose uptake.
AB  - We investigated the effect of angiotensin-converting enzyme inhibitors on glucose
      uptake regulation as well as the effect of bradykinin (BK) on glucose uptake and
      its regulation by using inhibitors of phospholipase C, BK B2 receptor, protein
      kinase C, phosphatidylinositol 3-kinase, tyrosine kinase, and intracellular
      Ca(2+). We measured 2-deoxyglucose uptake by using L(6) skeletal muscle cells. In
      the presence of 1 nmol/L of insulin, 1 micromol/L of enalaprilat enhanced insulin
      induced glucose uptake from 89.2+/-8. 1 to 138.0+/-13.6 pmol/h per mg protein.
      The stimulation of glucose uptake with enalaprilat was blocked to 92.7+/-7.8
      pmol/h per mg protein by 10 micromol/L HOE 140 (a BK B2 receptor antagonist). In
      the presence of 1 nmol/L of insulin, exposure to 10 micromol/L BK stimulated
      glucose uptake from 89.2+/-8.1 to 171.6+/-10.1 pmol/h per mg protein. However, in
      the absence of insulin, BK could not enhance glucose uptake. One hundred
      nanomoles per liter of tyrphostin A-23 and genistein, which are tyrosine kinase
      inhibitors, significantly decreased the BK-induced glucose uptake from 142.0+/
      8.4 to 87.6+/-6. 4 and 85.2+/-7.3 pmol/h per mg protein, respectively. BK-induced
      glucose uptake was inhibited significantly by 10 micromol/L U73122 (a
      phospholipase C antagonist) from 142.0+/-8.4 to 95.7+/-9.5 pmol/h per mg protein.
      One and 20 micromol/L of TMB-8 (an intracellular calcium antagonist)
      significantly decreased BK-induced glucose uptake from 142.0+/-8.4 to 108.0+/-9.6
      and 100.8+/-11.4 pmol/h per mg protein. Angiotensin-converting enzyme inhibitors
      enhanced insulin-induced glucose uptake via the BK B2 receptor. BK-stimulated
      glucose uptake is related to phospholipase C, tyrosine kinase, and an increase in
      intracellular calcium.

PMID- 10948085
TI  - Close relationship of abnormal glucose tolerance with endothelial dysfunction in
      hypertension.
AB  - Hypertension is frequently accompanied by left ventricular hypertrophy,
      endothelial dysfunction, and abnormal glucose metabolism. However, no study has
      examined the relative pathological significance of left ventricular hypertrophy
      and abnormal glucose metabolism on endothelial dysfunction in hypertension. This
      study was conducted to evaluate whether abnormal glucose tolerance assessed by 75
      g oral glucose tolerance test or left ventricular hypertrophy is more closely
      associated with endothelial dysfunction in never-treated hypertensive patients
      without elevated fasting blood glucose. We studied 107 unmedicated hypertensive
      patients (mean age, 54+/-10 years) whose fasting blood glucose was <7.0 mmol/L.
      Endothelial function was assessed by change in brachial artery diameter in
      response to reactive hyperemia, and left ventricular mass index was determined by
      ultrasonography. Simple linear regression analysis demonstrated that endothelial
      function significantly correlated with left ventricular mass index and 2-hour
      blood glucose in 75-g oral glucose tolerance test, but not with fasting blood
      glucose. Multiple linear regression analysis revealed that endothelial function
      significantly correlated with 2-hour blood glucose (beta=-2.68, P<0.05) after we
      controlled for other clinical variables. Patients were divided into 3 groups
      according to 2-hour blood glucose levels. Endothelial function was more impaired
      in patients with diabetes (n=12; 4.7+/-1.8%) and in those with impaired glucose
      tolerance (n=31; 6.3+/-2.9%) than in those with normal glucose tolerance (n=64;
      8.4+/-4.5%) (P<0.05), but left ventricular mass index was similar in these 3
      groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test,
      rather than left ventricular hypertrophy, may have direct pathophysiological
      relevance to endothelial dysfunction in borderline to moderate hypertensive
      patients.

PMID- 10948086
TI  - Interactions between blood cells and retinal endothelium in endotoxic sepsis.
AB  - Platelets and leukocytes are thought to play a leading role in the pathogenesis
      of many inflammatory conditions. To recruit flowing blood cells to the
      inflammatory region, it would be necessary for them to interact with vascular
      endothelial cells. Recently, many reports have indicated the resistance of
      spontaneous hypertensive rats (SHR) to endotoxic sepsis. Their resistance might
      be derived from suppressed interaction between these blood cells and endothelial
      cells. Therefore, SHR and age-matched Wistar-Kyoto rats (WKY) were induced with
      endotoxic sepsis by intravenous injection of lipopolysaccharide (LPS). At 4, 12,
      24, and 48 hours after induction, leukocyte-endothelial interactions in the
      retina were evaluated in vivo with acridine orange digital fluorography.
      Fluorescently labeled platelets were also injected to investigate platelet
      endothelial interactions in the retina in endotoxic sepsis. Leukocyte rolling in
      SHR after LPS injection was significantly suppressed; the maximum number of
      rolling leukocytes was reduced by 80.1% at 12 hours after LPS injection in SHR
      compared with WKY. Subsequent leukocyte infiltration into the vitreous cavity was
      significantly inhibited in SHR. Furthermore, platelet-endothelial interactions in
      the retina were also suppressed in SHR treated with LPS. The maximum numbers of
      rolling and adherent platelets were reduced by 59.5% and 62.6%, respectively, in
      SHR compared with WKY. In both strains, leukocyte- and platelet-endothelial
      interactions were substantially inhibited by the blocking of P-selectin. These
      suppressed interactions could contribute to the reduction of leukocyte- and
      platelet-mediated tissue injury in endotoxic sepsis in SHR, resulting in their
      resistance to endotoxemia.

PMID- 10948087
TI  - Angiotensin in the nucleus tractus solitarii contributes to neurogenic
      hypertension caused by chronic nitric oxide synthase inhibition.
AB  - Activation of the sympathetic nervous system and renin-angiotensin system has
      been suggested to contribute to the hypertension caused by chronic nitric oxide
      synthase inhibition. The aim of the present study was to determine whether
      angiotensin within the nucleus tractus solitarii (NTS) plays a role in activation
      of the sympathetic nervous system in this model. Rats were treated with N(omega)
      nitro-L-arginine methyl ester (L-NAME, 100 mg. kg(-1). d(-1) in drinking water)
      for 2 weeks. Experiments were performed on anesthetized rats with denervated
      arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate, and
      renal sympathetic nerve activity (RSNA) were measured. Microinjection of an
      angiotensin II type 1 (AT(1)) receptor antagonist (CV11974) or an angiotensin II
      type 2 (AT(2)) receptor antagonist (PD123319) into the depressor region within
      the NTS (identified by prior injection of L-glutamate) was performed.
      Microinjection of CV11974, but not of PD123319, produced greater decreases in
      arterial pressure, heart rate, and RSNA in L-NAME-treated rats than in control
      rats. The administration of hexamethonium resulted in a larger fall in arterial
      pressure in L-NAME-treated rats than in control rats. The ACE mRNA level in the
      brain stem was greater in L-NAME-treated rats than in control rats. These results
      suggest that increased sympathetic nerve activity plays a role in hypertension
      caused by chronic nitric oxide synthase inhibition and that activation of the
      renin-angiotensin system in the NTS is involved at least in part in this
      increased sympathetic nerve activity via AT(1) receptors.

PMID- 10948088
TI  - Nitric oxide and cardiac autonomic control in humans.
AB  - Cardiac autonomic control is of prognostic significance in cardiac disease, yet
      the control mechanisms of this system remain poorly defined. Animal data suggest
      that nitric oxide (NO) modulates cardiac autonomic control. We investigated the
      influence of NO on the baroreflex control of heart rate in healthy human
      subjects. In 26 healthy male volunteers (mean age, 23+/-5 years), we measured
      heart rate variability and baroreflex sensitivity during inhibition of endogenous
      NO production with N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg per hour) and
      during exogenous NO donation with sodium nitroprusside (1 to 3 mg/h). Increases
      from baseline (Delta) in high-frequency (HF) indexes of heart rate variability
      were smaller with L-NMMA in comparison to an equipressor dose of the control
      vasoconstrictor phenylephrine (12 to 42 microg/kg per hour): Deltaroot mean
      square of successive RR interval differences (DeltaRMSSD)=23+/-32 versus 51+/-48
      ms (P<0.002); Deltapercentage of successive RR interval differences >50 ms
      (DeltapNN50)=5+/-15% versus 14+/-12% (P<0.05); and DeltaHF normalized power=-2+/
      7 versus 9+/-8 normalized units (P<0.01), respectively. Relative preservation of
      these indexes was observed during unloading of the baroreflex with sodium
      nitroprusside compared with a matched fall in blood pressure produced by a
      control vasodilator, hydralazine (9 to 18 mg/h): DeltaRMSSD=-8+/-8 versus -24+/
      15 ms (P<0.001); DeltapNN50=-6+/-11% versus -15+/-19% (P<0.01); DeltaHF
      normalized power=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively.
      The change in cross-spectral alpha-index calculated as the square root of the
      ratio of RR interval power to systolic spectral power in the HF band (although
      not alpha-index calculated in the same way for the low-frequency bands or
      baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated
      with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg,
      respectively; P<0.02) and with sodium nitroprusside compared with hydralazine
      (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In conclusion, these
      data demonstrate that NO augments cardiac vagal control in humans.

PMID- 10948089
TI  - Nifedipine increases cytochrome P4502C expression and endothelium-derived
      hyperpolarizing factor-mediated responses in coronary arteries.
AB  - In addition to NO and prostacyclin, endothelial cells release a factor that
      elicits vasodilatation by hyperpolarizing the underlying vascular smooth muscle
      cells. In some vascular beds, this so-called endothelium-derived hyperpolarizing
      factor (EDHF) displays the characteristics of a cytochrome P450 (CYP)-derived
      arachidonic acid metabolite, such as an epoxyeicosatrienoic acid. Native porcine
      and cultured human coronary artery endothelial cells were screened for CYP
      epoxygenases, and CYP2B, CYP2C, and CYP2J were detected with reverse
      transcription-polymerase chain reaction. The CYP inducer beta-naphthoflavone and
      the Ca(2+) antagonist nifedipine significantly increased CYP2C mRNA but did not
      change the expression of CYP2J or CYP2B. To determine the relationship between
      CYP2C expression and EDHF production in native endothelial cells, we incubated
      porcine coronary arteries with nifedipine. Nifedipine enhanced endothelial CYP2C
      protein expression, as well as the generation of 11,12-epoxyeicosatrienoic acid.
      In organ bath experiments, pretreatment with nifedipine enhanced bradykinin
      induced, EDHF-mediated relaxations as well as the concomitant hyperpolarization
      of smooth muscle cells. The specific CYP2C9 inhibitor sulfaphenazole, on the
      other hand, significantly attenuated EDHF-mediated hyperpolarization and
      relaxation. These results demonstrate that in porcine coronary arteries, the
      elevated expression of a CYP epoxygenase, homologous to CYP2C8/9, is associated
      with enhanced EDHF-mediated hyperpolarization in response to bradykinin.
      Therefore, we propose that an isozyme of CYP2C is the most likely candidate for
      the CYP-dependent EDHF synthase in porcine coronary arteries.

PMID- 10948090
TI  - Renal changes induced by a cyclooxygenase-2 inhibitor during normal and low
      sodium intake.
AB  - Cyclooxygenase-2 (COX-2) has been identified in renal tissues under normal
      conditions, with its expression enhanced during sodium restriction. To evaluate
      the role of COX-2-derived metabolites in the regulation of renal function, we
      infused a selective inhibitor (nimesulide) in anesthetized dogs with normal or
      low sodium intake. The renal effects elicited by nimesulide and a non-isozyme
      specific inhibitor (meclofenamate) were compared during normal sodium intake. In
      ex vivo assays, meclofenamate, but not nimesulide, prevented the platelet
      aggregation elicited by arachidonic acid. During normal sodium intake, nimesulide
      infusion (n=6) had no effects on arterial pressure or renal hemodynamics but did
      reduce urinary sodium excretion, urine flow rate, and fractional lithium
      excretion. In contrast, nimesulide administration increased arterial pressure and
      decreased renal blood flow, urine flow rate, and fractional lithium excretion
      during low sodium intake (n=6). COX-2 inhibition reduced urinary prostaglandin
      E(2) excretion in both groups but did not modify plasma renin activity in dogs
      with low (8.1+/-1.1 ng angiotensin I. mL(-1). h(-1)) or normal (1.8+/-0.4 ng
      angiotensin I. mL(-1). h(-1)) sodium intake. Meclofenamate infusion in dogs with
      normal sodium intake (n=8) induced a greater renal hemodynamic effect than
      nimesulide infusion. These results suggest that COX-2-derived metabolites (1) are
      involved in the regulation of sodium excretion in dogs with normal sodium intake,
      (2) play an important role in the regulation of renal hemodynamic and excretory
      function in dogs with low sodium intake, and (3) are not involved in the
      maintenance of the high renin levels during a long-term decrease in sodium
      intake.

PMID- 10948091
TI  - Effect of bosentan on NF-kappaB, inflammation, and tissue factor in angiotensin
      II-induced end-organ damage.
AB  - Reports on the effectiveness of endothelin receptor blockers in angiotensin (Ang)
      II-induced end-organ damage are conflicting, and the mechanisms involved are
      uncertain. We tested the hypothesis that endothelin (ET)(A/B) receptor blockade
      with bosentan (100 mg/kg by gavage after age 4 weeks) ameliorates cardiac and
      renal damage by decreasing inflammation in rats harboring both human renin and
      angiotensinogen genes (dTGR). Furthermore, we elucidated the effect of bosentan
      on tissue factor (TF), which is a key regulator of the extrinsic coagulation
      cascade. We compared bosentan with hydralazine (80 mg/L in the drinking water for
      3 weeks) as a blood pressure control. Untreated dTGR featured hypertension, focal
      necrosis in heart and kidney, and a 45% mortality rate (9 of 20) at age 7 weeks.
      Compared with Sprague-Dawley controls, both systolic blood pressure and 24-hour
      albuminuria were increased in untreated dTGR (203+/-8 versus 111+/-2 mm Hg and
      67.1+/-8.6 versus 0.3+/-0.06 mg/d at week 7, respectively). Bosentan and
      hydralazine both reduced blood pressure and cardiac hypertrophy. Mortality rate
      was markedly reduced by bosentan (1/15) and partially by hydralazine (4/15).
      However, only bosentan decreased albuminuria and renal injury. Untreated and
      hydralazine-treated dTGR showed increased nuclear factor (NF)-kappaB and AP-1
      expression in the kidney and heart; the p65 NF-kappaB subunit was increased in
      the endothelium, vascular smooth muscles cells, infiltrating cells, glomeruli,
      and tubules. In the heart and kidney, ET(A/B) receptor blockade inhibited NF
      kappaB and AP-1 activation compared with hydralazine treatment. Macrophage
      infiltration, ICAM-1 expression, and the integrin expression on infiltrating
      cells were markedly reduced. Renal vasculopathy was accompanied by increased
      tissue factor expression on macrophages and vessels of untreated and hydralazine
      treated dTGR, which was markedly reduced by bosentan. Thus, ET(A/B) receptor
      blockade inhibits NF-kappaB and AP-1 activation and the NF-kappaB- and/or AP-1
      regulated genes ICAM-1, VCAM-1, and TF, independent of blood pressure-related
      effects. We conclude that Ang II-induced NF-kappaB and AP-1 activation and
      subsequent inflammation and coagulation involve at least in part the ET(A/B)
      receptors.

PMID- 10948093
TI  - Relationship between skin color and blood pressure in egyptian adults: results
      from the national hypertension project.
AB  - In many, but not all societies, dark skin color is associated with high blood
      pressure. Whether the association between skin color and blood pressure is
      independent of known determinants of blood pressure remains controversial. We
      examined the association between skin color and blood pressure in 835 Egyptian
      adults (370 men and 465 women) participating in the National Hypertension
      Project, a national survey of hypertension prevalence and blood pressure-related
      complications conducted in Egypt during 1991-1993. Skin color was assessed by
      measuring the concentration of cutaneous melanin in an unexposed area with the
      use of reflectance spectrophotometry. Higher concentrations of melanin were
      associated with lower body mass index, less education, manual labor (among men),
      and a lower urinary sodium-to-potassium ratio (among women). In multivariate
      regression analyses adjusted for age, body mass index, and education, there was a
      significant nonlinear association between blood pressure and skin color among
      women; in the lower to intermediate range of skin pigmentation, both systolic and
      diastolic blood pressures were higher in women with greater concentrations of
      cutaneous melanin. In men, blood pressure was not associated with skin color.
      When we used a subjective assessment of skin color, there was no significant
      difference in blood pressure between black-skinned Egyptians (predominantly of
      Nubian descent) and fair-skinned Egyptians for either gender. While the
      significant relationship in women appeared to be independent of known risk
      factors for hypertension, residual confounding may explain the association.

PMID- 10948092
TI  - Ascorbic acid and glutathione modulate the biological activity of S
      nitrosoglutathione.
AB  - Ascorbic acid and glutathione (GSH) are important determinants of the
      intracellular redox state, and both are known to accelerate the decomposition of
      S-nitrosoglutathione (GSNO), an endogenous adduct of nitric oxide (NO). The
      implications of these observations for GSNO bioactivity are not yet clear. We
      investigated the effect of ascorbic acid and GSH on GSNO bioactivity by using a
      bioassay with isolated segments of guinea pig aorta suspended in organ chambers.
      Arterial segments demonstrated relaxation to GSNO (0.1 micromol/L) that was
      significantly enhanced by 300 micromol/L ascorbic acid (71+/-6% versus 53+/-6%,
      P<0.05) but not GSH. Both ascorbic acid and GSH significantly shortened the
      duration of arterial relaxation in response to 0.1 micromol/L GSNO (from >120
      minutes to 22.5+/-3.5 and 36.3+/-4.3 minutes, respectively; P<0.05), consistent
      with accelerated decomposition of GSNO that was confirmed spectrophotometrically.
      The effect of ascorbic acid was abrogated by either DTPA or the copper(I)
      specific agent bathocuproine but not deferoxamine, indicating a dependence on the
      availability of redox-active copper. Consistent with this notion, the action of
      ascorbic acid on GSNO bioactivity was also supported by copper-zinc superoxide
      dismutase, a physiologically relevant source of copper. In contrast, the effect
      of GSH on GSNO degradation and GSNO-mediated arterial relaxation was independent
      of transition metal ions, because DTPA had no effect. These data indicate that
      both ascorbic acid and GSH modulate GSNO bioactivity and suggest a distinction
      between the mechanism of GSNO degradation by ascorbic acid or GSH. Whereas both
      ascorbic acid and GSH accelerate the degradation of GSNO, only ascorbic acid is
      dependent on the presence of transition metal ions.

PMID- 10948094
TI  - Circulating heat shock protein 60 is associated with early cardiovascular
      disease.
AB  - The phylogenetically conserved nature of heat shock proteins (Hsp) has led to the
      proposition that they may provide a link between infection and the inflammatory
      component to vascular disease. Hypertension is associated with atherosclerosis.
      Here, we measured circulating heat shock protein and heat shock protein antibody
      levels in association with borderline hypertension. Seventy-two men with
      borderline hypertension patients and 75 normotensive control subjects (diastolic
      blood pressure 85 to 94 and <80 mm Hg, respectively) were selected from a
      population-screening program. The levels of Hsp60; Hsp70; and anti-human Hsp60,
      anti-human Hsp70, and anti-mycobacterial Hsp65 antibodies were determined with
      enzyme immunoassay. The presence of carotid atherosclerosis and the intima-media
      thickness values were determined with ultrasonography. A major novel observation
      in this report was the detection of circulating Hsp60, which was present at a
      significantly enhanced level in patients with borderline hypertension.
      Furthermore, serum Hsp60 was associated with intima-media thicknesses (P<0.01).
      Anti-Hsp65 antibody levels were higher in borderline hypertension (P<0.001),
      whereas Hsp70 and anti-Hsp70 antibody levels did not differ. In contrast to anti
      Hsp65 antibody, anti-Hsp60 antibody levels were lower in borderline hypertension
      (P<0.03), although the difference was quantitatively small. None of the
      parameters evaluated were associated with atherosclerosis, metabolic factors, or
      smoking. We identified elevated Hsp60 levels in patients with borderline
      hypertension and an association between early atherosclerosis and Hsp60 levels.
      The physiological role of Hsp60 release has yet to be defined, but given the
      proinflammatory properties, these proteins could be involved in the
      induction/progression of both hypertension and atherosclerosis, as well as being
      markers for early cardiovascular disease.

PMID- 10948096
TI  - Characterization of a shiga toxin 2e-converting bacteriophage from an Escherichia
      coli strain of human origin.
AB  - An infectious Shiga toxin (Stx) 2e-converting bacteriophage (phiP27) was isolated
      from Stx2e-producing Escherichia coli ONT:H(-) isolate 2771/97 originating from a
      patient with diarrhea. The phage could be transduced to E. coli laboratory strain
      DH5alpha, and we could show that lysogens were able to produce biologically
      active toxin in a recA-dependent manner. By DNA sequence analysis of a 6,388-bp
      HindIII restriction fragment of phiP27, we demonstrated that the stx(2e) gene was
      located directly downstream of ileZ and argO tRNA genes. Although no analogue of
      an antiterminator Q encoding gene was present on this fragment, a lysis cassette
      comprising two holin genes which are related to the holin genes of Pseudomonas
      aeruginosa phage phiCTX and a gene homologous to the endolysin gene gp19 of phage
      PS3 were detected. The results of our study demonstrated for the first time that
      Stx2e can be encoded in the genome of an infectious bacteriophage.

PMID- 10948095
TI  - Bacterial quorum sensing in pathogenic relationships.

PMID- 10948097
TI  - Structural analysis of phage-borne stx genes and their flanking sequences in
      shiga toxin-producing Escherichia coli and Shigella dysenteriae type 1 strains.
AB  - The stx-flanking regions of 49 Shiga toxin-producing Escherichia coli strains and
      nine Shigella dysenteriae serotype 1 strains containing either stx, stx(1),
      stx(2), or stx(2) variant genes, were examined. We analyzed these regions by PCR
      using a set of primers with one primer specific for the respective stx gene and a
      second primer complementary to sequences of Stx phages H-19B and 933W. We further
      characterized the amplification products by restriction endonuclease digestion
      and nucleotide sequencing. PCR products of stx(1)-containing E. coli strains of
      serogroups O157, O26, and 0103 showed the same lengths and similar restriction
      patterns. However, we failed to amplify the 3' stx-flanking region in stx(1)
      harboring E. coli O111:H(-) strains. Stx2-producing E. coli strains revealed
      amplification products of different lengths and restriction patterns, suggesting
      greater heterogeneity than in stx(1)-positive strains. We also obtained specific
      PCR products for two Stx2c-producing and seven Stx2f-producing E. coli strains
      when they were subjected to PCR analysis. In nine S. dysenteriae type 1 strains,
      H-19B- and 933W-specific primers amplified only the 3' stx-flanking region. The
      results of our study demonstrate that the stx genes of all strains investigated
      are continuous with phage sequences. Whereas almost all strains except E. coli
      O111:H(-) strains were associated with a S-like gene, association with Q could
      not be demonstrated in nine S. dysenteriae type 1 strains and three E. coli
      strains. Furthermore, we showed that the organization of the stx-flanking regions
      is similar in all strains investigated, whereas fine-structure analysis showed
      subtle differences among the sequences examined. Our results support the
      hypothesis that stx genes in E. coli and S. dysenteriae are generally phage
      borne.

PMID- 10948098
TI  - Adherence of Staphylococcus aureus to endothelial cells: influence of capsular
      polysaccharide, global regulator agr, and bacterial growth phase.
AB  - The adherence of Staphylococcus aureus to human endothelial cells (EC) is
      probably an important step in the pathogenesis of systemic staphylococcal
      infections. We examined the influence of type 5 capsular polysaccharide (CP5)
      production, the global regulator agr, and the bacterial growth phase on S. aureus
      adherence to EC. Whereas S. aureus Newman showed maximal adherence to EC in the
      logarithmic phase of growth, an isogenic agr mutant showed maximal adherence in
      the stationary growth phase. S. aureus adherence to EC and CP5 expression were
      negatively correlated: a mutation in the agr locus diminished CP5 production and
      led to increased adherence. Likewise, induction of CP5 expression by addition of
      NaCl to the growth medium resulted in reduced staphylococcal adherence to EC. S.
      aureus Newman cells that adhered to EC did not express CP5. A Newman cap5O mutant
      was acapsular and showed significantly greater adherence to EC than the parental
      strain did (P<0.005). Complementation of the cap5O mutation in trans restored CP5
      expression and reduced EC adherence to a level similar to that of the parental
      strain. The enhanced adherence shown by the cap5O mutant was similar in magnitude
      to that of the agr mutant or the cap5O agr double mutant. Cells of the cap5O
      mutant and cap5O agr double mutant harvested from stationary-phase cultures
      adhered significantly better than did cells harvested in the exponential growth
      phase. These data are consistent with the postexponential and agr-independent
      expression by S. aureus of at least one putative EC adhesin, whose binding domain
      may be masked by CP5.

PMID- 10948099
TI  - Coincubation of human spermatozoa with Chlamydia trachomatis in vitro causes
      increased tyrosine phosphorylation of sperm proteins.
AB  - Elementary bodies (EBs) of the obligate intracellular bacterium Chlamydia
      trachomatis are responsible for the first step of attachment to host cells. We
      have studied the effects of EBs on human sperm protein tyrosine phosphorylation,
      which is important to sperm function. Indirect immunofluorescence using
      antiphosphotyrosine antibodies showed that serovar E, but not LGV, caused
      increased tyrosine phosphorylation which was localized to the sperm tail region.
      Immunoblotting revealed that serovar E caused a marked increase in tyrosine
      phosphorylation of 80- and 95-kDa sperm proteins, whereas serovar LGV caused
      increased phosphorylation of only the 80-kDa moiety. Considering the importance
      of tyrosine phosphorylation for sperm capacitation and other aspects of sperm
      function, we conclude that EBs may affect these events.

PMID- 10948100
TI  - Recombinant Mycobacterium bovis BCG expressing pertussis toxin subunit S1 induces
      protection against an intracerebral challenge with live Bordetella pertussis in
      mice.
AB  - The recent development of acellular pertussis vaccines has been a significant
      improvement in the conventional whole-cell diphtheria-pertussis-tetanus toxoid
      vaccines, but high production costs will limit its widespread use in developing
      countries. Since Mycobacterium bovis BCG vaccination against tuberculosis is used
      in most developing countries, a recombinant BCG-pertussis vaccine could be a more
      viable alternative. We have constructed recombinant BCG (rBCG) strains expressing
      the genetically detoxified S1 subunit of pertussis toxin 9K/129G (S1PT) in fusion
      with either the beta-lactamase signal sequence or the whole beta-lactamase
      protein, under control of the upregulated M. fortuitum beta-lactamase promoter,
      pBlaF*. Expression levels were higher in the fusion with the whole beta-lactamase
      protein, and both were localized to the mycobacterial cell wall. The expression
      vectors were relatively stable in vivo, since at two months 85% of the BCG
      recovered from the spleens of vaccinated mice maintained kanamycin resistance.
      Spleen cells from rBCG-S1PT-vaccinated mice showed elevated gamma interferon (IFN
      gamma) and low interleukin-4 (IL-4) production, as well as increased
      proliferation, upon pertussis toxin (PT) stimulation, characterizing a strong
      antigen-specific Th1-dominant cellular response. The rBCG-S1PT strains induced a
      low humoral response against PT after 2 months. Mice immunized with rBCG-S1PT
      strains displayed high-level protection against an intracerebral challenge with
      live Bordetella pertussis, which correlated with the induction of a PT-specific
      cellular immune response, reinforcing the importance of cell-mediated immunity in
      the protection against B. pertussis infection. Our results suggest that rBCG
      expressing pertussis antigens could constitute an effective, low-cost combined
      vaccine against tuberculosis and pertussis.

PMID- 10948102
TI  - Anti-HSP70 autoantibody formation by B-1 cells in Toxoplasma gondii-infected
      mice.
AB  - Formation of anti-Toxoplasma gondii HSP70 (TgHSP70) antibody cross-reactive to
      mouse HSP70 (mHSP70) was observed in the sera of BALB/c (a resistant strain) and
      C57BL/6 (B6; a susceptible strain) mice after peroral infection with T. gondii
      cysts of the Fukaya strain. The levels of anti-mHSP70 immunoglobulin G (IgG)
      autoantibody production in B6 mice were higher than those in BALB/c mice. The
      isotype and subclass of IgG of anti-TgHSP70 monoclonal antibodies cross-reactive
      to mHSP70 were mu and gamma3. Anti-mHSP70 autoantibody in T. gondii-infected
      BALB/c and B6 mice was shown to be produced by the CD5(+) subset of B cells (B-1a
      cells) but not by conventional B cells (B-2 cells). The epitopes recognized by
      anti-mHSP70 autoantibody were located primarily in the C-terminal fragment of
      mHSP70.

PMID- 10948101
TI  - Attenuated Shigella flexneri 2a vaccine strain CVD 1204 expressing colonization
      factor antigen I and mutant heat-labile enterotoxin of enterotoxigenic
      Escherichia coli.
AB  - A multivalent live oral vaccine against both Shigella spp. and enterotoxigenic
      Escherichia coli (ETEC) is being developed based on the hypothesis that
      protection can be achieved if attenuated shigellae express ETEC fimbrial
      colonization factors and genetically detoxified heat-labile toxin from a human
      ETEC isolate (LTh). Two detoxified derivatives of LTh, LThK63 and LThR72, were
      engineered by substitution-serine to lysine at residue 63, or lysine to arginine
      at residue 72. The genes encoding these two derivatives were cloned separately on
      expression plasmids downstream from the CFA/I operon. Following electroporation
      into S. flexneri 2a vaccine strain CVD 1204, coexpression of CFA/I and LThK63 or
      LThR72 was demonstrated by Western blot analysis, GM(1) binding assays, and
      agglutination with anti-CFA/I antiserum. Hemagglutination and electron microscopy
      confirmed surface expression of CFA/I. Guinea pigs immunized intranasally on days
      0 and 15 with CVD 1204 expressing CFA/I and LThK63 or LThR72 exhibited high
      titers of both serum immunoglobulin G (IgG) and mucosal secretory IgA anti-CFA/I;
      40% of the animals produced antibodies directed against LTh. All immunized guinea
      pigs also produced mucosal IgA (in tears) and serum IgG anti-S. flexneri 2a O
      antibodies. Furthermore, all immunized animals were protected from challenge with
      wild-type S. flexneri 2a. This prototype Shigella-ETEC hybrid vaccine
      demonstrates the feasibility of expressing multiple ETEC antigens on a single
      plasmid in an attenuated Shigella vaccine strain and engendering immune responses
      against both the heterologous antigens and vector strain.

PMID- 10948103
TI  - Aggregation substance promotes adherence, phagocytosis, and intracellular
      survival of Enterococcus faecalis within human macrophages and suppresses
      respiratory burst.
AB  - The aggregation substance (AS) of Enterococcus faecalis, encoded on sex pheromone
      plasmids, is a surface-bound glycoprotein that mediates aggregation between
      bacteria thereby facilitating plasmid transfer. Sequencing of the pAD1-encoded
      Asa1 revealed that this surface protein contains two RGD motifs which are known
      to ligate integrins. Therefore, we investigated the influence of AS on the
      interaction of E. faecalis with human monocyte-derived macrophages which
      constitutively express beta(2) integrins (e.g., CD18). AS was found to cause a
      greater-than-fivefold increase in enterococcal adherence to macrophages and a
      greater-than-sevenfold increase in phagocytosis. Adherence was mediated by an
      interaction between the RGD motif and the integrin CD11b/CD18 (complement
      receptor type 3) as demonstrated by inhibition studies with monoclonal antibodies
      and RGD peptide. AS-bearing enterococci were significantly more resistant to
      macrophage killing during the first 3 h postinfection, probably due to inhibition
      of the respiratory burst as indicated by reduced concentrations of superoxide
      anion.

PMID- 10948104
TI  - CP30, a cysteine proteinase involved in Trichomonas vaginalis cytoadherence.
AB  - We describe here the participation of a Trichomonas vaginalis 30-kDa proteinase
      (CP30) with affinity to the HeLa cell surface in attachment of this parasite to
      host epithelial cells. The CP30 band is a cysteine proteinase because its
      activity was inhibited by E-64, a thiol proteinase inhibitor. In two-dimensional
      substrate gel electrophoresis of total extracts of the trichomonad isolate CNCD
      147, three spots with proteolytic activity were detected in the 30-kDa region, in
      the pI range from 4.5 to 5.5. Two of the spots (pI 4.5 and 5.0) bound to the
      surfaces of fixed HeLa cells corresponding to the CP30 band. The immunoglobulin G
      fraction of the rabbit anti-CP30 antiserum that recognized a 30-kDa band by
      Western blotting and immunoprecipitated CP30 specifically inhibited trichomonal
      cytoadherence to HeLa cell monolayers in a concentration-dependent manner and
      reacted with CP30 at the parasite surface. CP30 degraded proteins found on the
      female urogenital tract, including fibronectin, collagen IV, and hemoglobin.
      Interestingly, CP30 digested fibronectin and collagen IV only at pH levels
      between 4.5 and 5.0. Moreover, trichomonosis patients whose diagnosis was
      confirmed by in vitro culture possessed antibody to CP30 in both sera and vaginal
      washes, and CP30 activity was found in vaginal washes. Our results suggest that
      surface CP30 is a cysteine proteinase necessary for trichomonal adherence to
      human epithelial cells.

PMID- 10948105
TI  - Extract of Nippostrongylus brasiliensis stimulates polyclonal type-2
      immunoglobulin response by inducing De novo class switch.
AB  - Infection with the nematode parasite Nippostrongylus brasiliensis induces a
      pronounced type-2 T-cell response that is associated with marked polyclonal
      immunoglobulin E (IgE) and IgG1 production in mice. To examine the differential
      roles of the infection and products produced by nematodes, we investigated a
      soluble extract of N. brasiliensis for the ability to mediate this type-2
      response. We found that the extract induced a marked increase in IgE and IgG1
      levels, similar to that induced by the infection. The extract did not affect the
      level of IgG2a in serum, showing that the effect was specific to IgE and IgG1
      (type-2-associated immunoglobulin) rather than inducing a nonspecific increase in
      all immunoglobulin isotypes. This response was also associated with increased
      interleukin-4 production in vitro. These results confirm that the extract, like
      infection, is a strong inducer of polyclonal type-2 responses and a reliable
      model for investigating the regulation of nematode-induced responses. The extract
      induced the production of IgG1 when added to in vitro cultures of
      lipopolysaccharide-stimulated B cells. This provides evidence for the induction
      of class switch. It did not induce upregulation of IgG1 in naive (unstimulated) B
      cells or expand B cells in in vitro cultures. Analysis of DNA from the spleens of
      mice treated with the extract by digestion-circularization PCR demonstrated a
      marked increase in the occurrence of gamma1 switch region gene recombination in
      the cells in vivo. These results provide strong evidence that soluble worm
      products are able to mediate the marked polyclonal gamma1/epsilon response and
      that infection is not required to mediate this response. Furthermore, these data
      provide evidence that the soluble nematode extract induces this effect by causing
      de novo class switch of B cells and not by an expansion of IgG1 B cells or an
      increase in antibody production by IgG1 plasma cells.

PMID- 10948106
TI  - Antipeptide antibody responses following intranasal immunization: effectiveness
      of mucosal adjuvants.
AB  - Toxicity is a major factor limiting the development and use of potent adjuvants
      for human mucosally delivered vaccines. Novel adjuvant formulations have recently
      become available, and in the present study two have been used for intranasal
      immunization with a synthetic peptide immunogen (MAP-M2). This peptide represents
      a multiple antigenic peptide containing multiple copies of a mimotope M2, a
      peptide mimic of a conformational epitope of the fusion protein of measles virus.
      MAP-M2 was administered intranasally to experimental animals together with
      synthetic oligodeoxynucleotides containing unmethylated CpG motifs with or
      without a mutant of wild-type enterotoxin of Escherichia coli (LTR72). The
      combination of the mutant toxin LTR72 and the CpG repeats, codelivered with a
      peptide immunogen, induced both local and systemic peptide- and pathogen-specific
      humoral and cellular immune responses comparable to those obtained after
      intranasal immunization with the wild-type toxin LT. In addition, this
      combination of adjuvants induced a predominantly immunoglobulin G2a antibody
      response. If both the LTR72 and CpG adjuvants are shown to be safe for use in
      humans, this particular combination would appear to have potential as an adjuvant
      for mucosally delivered vaccines in humans.

PMID- 10948107
TI  - Phagocytic cell killing mediated by secreted cytotoxic factors of Vibrio
      cholerae.
AB  - Vibrio cholerae strain VB1 secretes a number of enzymes into the outside medium
      that utilize ATP as a substrate. Such enzymes are found in the outside medium
      during the mid-log phase of growth, when the optical density at 650 nm is about
      0.4, and they demonstrate nucleoside diphosphate kinase (Ndk), 5' nucleotidase,
      and adenylate kinase (Ak) activities. We report that the filtered growth medium
      of V. cholerae, as well as the flowthrough fraction of a green Sepharose column
      during fractionation of the growth medium, had very little cytotoxicity by itself
      towards macrophages and mast cells but exhibited significant cytotoxicity in the
      presence of exogenous ATP. Such fractions, harboring 5' nucleotidase, Ndk, and
      presumably other ATP-utilizing enzymes, demonstrated enhanced macrophage and mast
      cell death; periodate-oxidized-ATP (oATP)-treated macrophage and mast cells or
      such cells exposed to 0.1 mM Mg(2+), where surface-associated P2Z receptors could
      not be activated, were not susceptible to subsequent ATP addition. Microscopic
      visualization of mast cells clearly demonstrated cell morphological changes such
      as swelling, vacuolization, and nuclear fragmentation following treatment with
      ATP and the growth medium of V. cholerae; however, these effects were suppressed
      if the mast cells were pretreated with oATP. These results strongly imply that
      the secreted ATP-utilizing enzymes of V. cholerae modulate the external ATP
      levels of the macrophage and mast cells, leading to their accelerated death,
      presumably through activation of P2Z receptors. Thus, development of inhibitors
      for such enzymes may reduce the level of V. cholerae infection; alternatively,
      mutations in such genes may eliminate V. cholerae survival in the gut and
      contribute to a safer live vaccine.

PMID- 10948108
TI  - Allelic diversity of the two transferrin binding protein B gene isotypes among a
      collection of Neisseria meningitidis strains representative of serogroup B
      disease: implication for the composition of a recombinant TbpB-based vaccine.
AB  - The distribution of the two isotypes of tbpB in a collection of 108 serogroup B
      meningococcal strains belonging to the four major clonal groups associated with
      epidemic and hyperendemic disease (the ET-37 complex, the ET-5 complex, lineage
      III, and cluster A4) was determined. Isotype I strains (with a 1.8-kb tbpB gene)
      was less represented than isotype II strains (19.4 versus 80.6%). Isotype I was
      restricted to the ET-37 complex strains, while isotype II was found in all four
      clonal complexes. The extent of the allelic diversity of tbpB in these two groups
      was studied by PCR restriction analysis and sequencing of 10 new tbpB genes. Four
      major tbpB gene variants were characterized: B16B6 (representative of isotype I)
      and M982, BZ83, and 8680 (representative of isotype II). The relevance of these
      variants was assessed at the antigenic level by the determination of cross
      bactericidal activity of purified immunoglobulin G preparations raised to the
      corresponding recombinant TbpB (rTbpB) protein against a panel of 27 strains (5
      of isotype I and 22 of isotype II). The results indicated that rTbpB
      corresponding to each variant was able to induce cross-bactericidal antibodies.
      However, the number of strains killed with an anti-rTbpB serum was slightly lower
      than that obtained with an anti-TbpA(+)B complex. None of the sera tested raised
      against an isotype I strain was able to kill an isotype II strain and vice versa.
      None of the specific antisera tested (anti-rTbpB or anti-TbpA(+)B complex) was
      able to kill all of the 22 isotype II strains tested. Moreover, using sera raised
      against the C-terminus domain of TbpB M982 (amino acids 352 to 691) or BZ83
      (amino acids 329 to 669) fused to the maltose-binding protein, cross-bactericidal
      activity was detected against 12 and 7 isotype II strains, respectively, of the
      22 tested. These results suggest surface accessibility of the C-terminal end of
      TbpB. Altogether, these results show that although more than one rTbpB will be
      required in the composition of a TbpB-based vaccine to achieve a fully cross
      bactericidal activity, rTbpB and its C terminus were able by themselves to induce
      cross-bactericidal antibodies.

PMID- 10948109
TI  - Protective immunity against congenital toxoplasmosis with recombinant SAG1
      protein in a guinea pig model.
AB  - Primary infection with Toxoplasma gondii during pregnancy can induce fetal
      pathology and abortion in both humans and animals. The present study describes
      the development of an experimental model of congenital toxoplasmosis in the
      guinea pig. In this animal model, we evaluated the protective effect of
      vaccination with a recombinant form of SAG1 against maternofetal transmission of
      tachyzoites. The presence of parasites in fetuses was determined by nested PCRs
      and by an in vivo readout after fetal brain homogenate injections in mice. The
      absence of parasites was demonstrated in 66 to 86% of fetuses derived from adult
      guinea pigs immunized with SAG1 and challenged with the mildly virulent T. gondii
      strain C56. In contrast, more than 80% of fetuses from mock-immunized guinea pigs
      were infected. The protection was not correlated with titers of antibody to SAG1.
      Our results indicated that this experimental model constitutes a relevant model
      for evaluation of vaccine candidates against congenital toxoplasmosis and that
      SAG1 elicits significant protection against maternofetal transmission.

PMID- 10948110
TI  - Serum amyloid P component prevents high-density lipoprotein-mediated
      neutralization of lipopolysaccharide.
AB  - Lipopolysaccharide (LPS) is an amphipathic macromolecule that is highly
      aggregated in aqueous preparations. LPS-binding protein (LBP) catalyzes the
      transfer of single LPS molecules, segregated from an LPS aggregate, to high
      density lipoproteins (HDL), which results in the neutralization of LPS. When
      fluorescein isothiocyanate-labeled LPS (FITC-LPS) is used, this transfer of LPS
      monomers to HDL can be measured as an increase in fluorescence due to dequenching
      of FITC-LPS. Recently, serum amyloid P component (SAP) was shown to neutralize
      LPS in vitro, although only in the presence of low concentrations of LBP. In this
      study, we show that SAP prevented HDL-mediated dequenching of FITC-LPS, even in
      the presence of high concentrations of LBP. Human bactericidal/permeability
      increasing protein (BPI), a very potent LPS-binding and -neutralizing protein,
      also prevented HDL-mediated dequenching of FITC-LPS. Furthermore, SAP inhibited
      HDL-mediated neutralization of both rough and smooth LPS in a chemiluminescence
      assay quantifying the LPS-induced priming of neutrophils in human blood. SAP
      bound both isolated HDL and HDL in serum. Using HDL-coated magnetic beads
      prebound with SAP, we demonstrated that HDL-bound SAP prevented the binding of
      LPS to HDL. We suggest that SAP, by preventing LPS binding to HDL, plays a
      regulatory role, balancing the amount of LPS that, via HDL, is directed to the
      adrenal glands.

PMID- 10948111
TI  - Antibody and cytokine responses to the cilium-associated respiratory bacillus in
      BALB/c and C57BL/6 mice.
AB  - The cilium-associated respiratory (CAR) bacillus is a gram-negative, gliding
      bacterium that causes persistent respiratory tract infections in rodents despite
      histologic and serologic evidence of a marked immune response. To assess humoral
      immunity and cytokine responses in CAR bacillus disease, 6-week-old female BALB/c
      and C57BL/6 mice were inoculated intratracheally with 10(5) CAR bacillus
      organisms. CAR bacillus-specific serum immunoglobulins (immunoglobulin M [IgM],
      IgG1, IgG2a, IgG2b, IgG3, and IgA) and local pulmonary cytokines (tumor necrosis
      factor alpha [TNF-alpha], gamma interferon [IFN-gamma], and interleukin-4 [IL-4])
      were evaluated by enzyme-linked immunosorbent assay every 7 days for 49 days.
      BALB/c mice developed CAR bacillus-induced lesions early in the course of disease
      that became more severe with time. Correlating with increasing disease severity,
      BALB/c mice had elevations in all antibody isotypes tested, and elevations in
      pulmonary TNF-alpha, IFN-gamma, and IL-4. C57BL/6 mice developed mild lesions
      with mild increases in serum IgM, IgG1, IgG2b, and IgG3 levels and minimally
      detectable IgG2a and IgA. Cytokine perturbations were not detected in C57BL/6
      mice. The persistence of infection in BALB/c mice with vigorous serum antibody
      responses and increased IFN-gamma and IL-4 responses suggests that humoral
      immunity and T-cell responses are ineffective at preventing CAR bacillus disease.
      Furthermore, the lackluster antibody responses and undetectable cytokine
      responses in C57BL/6 mice suggest that humoral immunity and T-cell responses are
      not critical in resistance to CAR bacillus-induced disease.

PMID- 10948112
TI  - Mucosal defense against gastrointestinal nematodes: responses of mucosal mast
      cells and mouse mast cell protease 1 during primary strongyloides venezuelensis
      infection in FcRgamma-knockout mice.
AB  - A possible role for the gamma subunit of immunoglobulin Fc receptors (FcR) in
      mucosal defenses against intestinal nematode parasites was studied using age
      matched FcRgamma-knockout (FcRgamma(-/-)) and wild-type (FcRgamma(+/+)) C57BL/6
      mice. Mice were infected subcutaneously with 3,000 infective larvae of
      Strongyloides venezuelensis, and the degree of infection was monitored by daily
      fecal egg counts and adult worm recovery on days 8 and 13 postinfection. Mucosal
      mast cell (MMC) responses were assayed by in situ intestinal mast cell counts in
      stained histological sections of the jejunum and by measuring mouse mast cell
      protease 1 (MMCP-1) release in serum using sandwich enzyme-linked immunosorbent
      assay. FcRgamma(-/-) mice had significantly higher egg counts (P<0.01) and
      numbers of adult worms (P<0.05) than FcRgamma(+/+) mice, but mastocytosis and
      serum MMCP-1 release were comparable. It was concluded that MMCP-1 release may be
      spontaneous, does not depend on mast cell degranulation via the FcRgamma
      signaling system, and appears to play no role in the expulsion of S.
      venezuelensis. The delay in worm expulsion in the FcRgamma(-/-) mice might be
      related to inability of the MMC to degranulate and release effector molecules
      other than MMCP-1, since FcRgamma deletion abrogates mast cell degranulative
      responses.

PMID- 10948113
TI  - Molecular cloning, sequencing, expression, and characterization of an immunogenic
      43-kilodalton lipoprotein of Bartonella bacilliformis that has homology to
      NlpD/LppB.
AB  - A recombinant clone expressing an immunoreactive antigen of Bartonella
      bacilliformis was isolated by screening a genomic DNA library with serum from a
      patient with the chronic verruga phase of bartonellosis. The clone, pBIPIM-17,
      contained a partial open reading frame that expressed an immunoreactive fusion
      protein. Subsequent rescreening of the library by plaque hybridization resulted
      in the isolation of recombinant clones that contain the entire open reading
      frame. The open reading frame (ORF-401) is capable of encoding a protein of 401
      amino acids with a predicted molecular mass of 43 kDa. The deduced amino acid
      sequence of the encoded protein was found to be highly homologous to a recently
      identified bacterial lipoprotein (LppB/NlpD) which has been associated with
      virulence. Evidence has been provided to show that the 43-kDa antigen of B.
      bacilliformis is a lipoprotein and that it is likely to use the same biosynthetic
      pathway as other bacterial lipoproteins. This is the first report to date that
      characterizes a lipoprotein of B. bacilliformis. The immunogenicity of the B.
      bacilliformis LppB homologue was demonstrated by Western blot analysis using sera
      from patients with clinical bartonellosis. Sera from patients who had a high
      titer for Bartonella henselae, the causative agent of bacillary angiomatosis and
      cat scratch disease, also recognized the recombinant 43-kDa antigen, suggesting
      that a homologue of this antigen is present in B. henselae. Using a cocktail of
      synthetic peptides corresponding to predicted major antigenic sites, polyclonal
      antiserum specific for the LppB homologue of B. bacilliformis was generated. This
      antiserum did not recognize the NlpD homologue of Escherichia coli or the 43-kDa
      antigen of B. henselae.

PMID- 10948114
TI  - Enhancement of clearance of bacteria from murine lungs by immunization with
      detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins.
AB  - Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-protein
      conjugates induced a significant rise of bactericidal anti-LOS antibodies in
      animals. This study reports the effect of active or passive immunization with the
      conjugates or their antiserum on pulmonary clearance of M. catarrhalis in an
      aerosol challenge mouse model. Mice were injected subcutaneously with dLOS
      tetanus toxoid (dLOS-TT), dLOS-high-molecular-weight proteins (dLOS-HMP) from
      nontypeable Haemophilus influenzae (NTHi), or nonconjugated materials in Ribi
      adjuvant and then challenged with M. catarrhalis strain 25238 or O35E or NTHi
      strain 12. Immunization with dLOS-TT or dLOS-HMP generated a significant rise of
      serum anti-LOS immunoglobulin G and 68% and 35 to 41% reductions of bacteria in
      lungs compared with the control (P<0.01) following challenge with homologous
      strain 25238 and heterologous strain O35E, respectively. Serum anti-LOS antibody
      levels correlated with its bactericidal titers against M. catarrhalis and
      bacterial CFU in lungs. Additionally, immunization with dLOS-HMP generated a 54%
      reduction of NTHi strain 12 compared with the control (P<0.01). Passive
      immunization with a rabbit antiserum against dLOS-TT conferred a significant
      reduction of strain 25238 CFU in lungs in a dose- and time-dependent pattern
      compared with preimmune serum-treated mice. Kinetic examination of lung tissue
      sections demonstrated that antiserum-treated mice initiated and offset
      inflammatory responses more rapidly than preimmune serum-treated mice. These data
      indicate that LOS antibodies (whether active or passive) play a major role in the
      enhancement of pulmonary clearance of different test strains of M. catarrhalis in
      mice. In addition, dLOS-HMP is a potential candidate for a bivalent vaccine
      against M. catarrhalis and NTHi infections.

PMID- 10948115
TI  - DNA-Based immunization with Trypanosoma cruzi complement regulatory protein
      elicits complement lytic antibodies and confers protection against Trypanosoma
      cruzi infection.
AB  - A complement regulatory protein (CRP) of Trypanosoma cruzi was evaluated as a
      vaccine candidate in a murine model of experimental T. cruzi infection.
      Recombinant CRP derived from an Escherichia coli expression system and a plasmid
      encoding the full-length crp structural gene under the control of a eukaryotic
      promoter were used to immunize BALB/c mice. Immunization with both protein and
      DNA vaccines resulted in a Th1-type T-cell response, comparable antibody titers,
      and similar immunoglobulin G isotype profiles. Only mice immunized with the crp
      DNA plasmid produced antibodies capable of lysing the parasites in the presence
      of complement and were protected against a lethal challenge with T. cruzi
      trypomastigotes. These results demonstrate the superiority of DNA immunization
      over protein immunization with the recombinant CRP. The work also supports the
      further investigation of CRP as a component of a multigene, anti-T. cruzi DNA
      vaccine.

PMID- 10948116
TI  - Expression and immunological analysis of the plasmid-borne mlp genes of Borrelia
      burgdorferi strain B31.
AB  - A lipoprotein gene family first identified in Borrelia burgdorferi strain 297,
      designated 2.9 LP and recently renamed mlp, was found on circular and linear
      plasmids in the genome sequence of B. burgdorferi strain B31-M1. Sequence
      analyses of the B31 mlp genes and physically linked variant gene families
      indicated that mlp gene heterogeneity is unique and unrelated to location or
      linkage to divergent sequences. Evidence of recombination between B31 mlp alleles
      was also detected. Northern blot analysis of cultured strain B31 indicated that
      the mlp genes were not expressed at a temperature (23 degrees C) characteristic
      of that of ticks in the environment. In striking contrast, expression of many mlp
      genes increased substantially when strain B31 was shifted to 35 degrees C, a
      temperature change mimicking that occurring in the natural transmission cycle of
      the spirochete from tick to mammal. Primer extension analysis of the mlp mRNA
      transcripts suggested that sigma 70-like promoters are involved in mlp expression
      during temperature shift conditions. Antibodies were made against strain B31 Mlp
      proteins within the first 4 weeks after experimental mouse infection.
      Importantly, Lyme disease patients also had serum antibodies reactive with
      purified recombinant Mlp proteins from strain B31, a result indicating that
      humans are exposed to Mlp proteins during infection. Taken together, the data
      indicate that strain B31 mlp genes encode a diverse array of lipoproteins which
      may participate in early infection processes in the mammalian host.

PMID- 10948117
TI  - Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells.
AB  - Previous studies led to the development of a model of contact-induced enhanced
      gonococcal invasion of human reproductive cells that utilizes the lutropin
      receptor (LHr) as both the induction signal for conversion to this enhanced
      gonococcal-invasion phenotype (Inv(+) GC) and as the specific Inv(+) GC uptake
      mechanism. This model proposes that gonococci express a surface feature that
      mimics human chorionic gonadotropin (hCG), the cognate ligand for LHr, and that
      this structure is responsible for the specific and productive interaction of GC
      with LHr. In this report, we identify a 13-kDa gonococcal protein with
      immunological similarities to hCG. The antiserum reactivity is specific since
      interaction with the 13-kDa gonococcal protein can be blocked by the addition of
      highly purified hCG. This gonococcal "hCG-like" protein, purified from two
      dimensional gels and by immunoprecipitation, was determined by N-terminal
      sequencing to be the ribosomal protein L12. We present evidence that gonococcal
      L12 is membrane associated and surface exposed in gonococci, as shown by
      immunoblot analysis of soluble and insoluble gonococcal protein and antibody
      adsorption studies with fixed GC. Using highly purified recombinant gonococcal
      L12, we show that preincubation of Inv(-) GC with micromolar amounts of rL12
      leads to a subsequent five- to eightfold increase in invasion of the human
      endometrial cell line, Hec1B. In addition, nanomolar concentrations of exogenous
      L12 inhibits gonococcal invasion to approximately 70% of the level in controls.
      Thus, we propose a novel cellular location for the gonococcal ribosomal protein
      L12 and concomitant function in LHr-mediated gonococcal invasion of human
      reproductive cells.

PMID- 10948118
TI  - Toxoids of streptococcal pyrogenic exotoxin A are protective in rabbit models of
      streptococcal toxic shock syndrome.
AB  - Streptococcal pyrogenic exotoxins (SPEs) are superantigens that have been
      implicated in causing streptococcal toxic shock syndrome (STSS). Most notably,
      SPE serotype A is made by nearly all M-protein serotype 1 and 3 streptococci, the
      M types most associated with the illness (these strains contain one or more other
      SPEs, and those proteins are likely also to contribute to disease). We have
      prepared double-, triple-, and hexa-amino-acid mutants of SPE A by PCR and other
      mutagenesis procedures. The sites chosen for mutation were solvent-exposed
      residues thought to be important for T-cell receptor (TCR) or major
      histocompatibility complex (MHC) class II interaction. These mutants were
      nonsuperantigenic for human peripheral blood mononuclear cells and rabbit and
      mouse splenocytes and were nonlethal in two rabbit models of STSS. In addition,
      these mutants stimulated protective antibody responses. Interestingly, mutants
      that altered toxin binding to MHC class II were more immunogenic than mutants
      altering TCR binding. Collectively, these studies indicate that multiple-site
      mutants of SPE A are toxoids that may have use in protecting against the toxin's
      effects in STSS.

PMID- 10948119
TI  - Genetic polymorphisms of group B streptococcus scpB alter functional activity of
      a cell-associated peptidase that inactivates C5a.
AB  - Many group B Streptococcus agalactiae strains and other pathogenic streptococci
      express a cell-associated peptidase that inactivates C5a (C5a-ase), the major
      neutrophil chemoattractant produced by activation of the complement cascade. Type
      III group B streptococci (GBS) can be classified genotypically into three
      restriction digest pattern types. Functional C5a-ase activity of GBS correlates
      with this genetic typing; therefore, we sought to identify a genetic basis for
      this phenomenon. Southern hybridization confirms that all type III GBS contain
      scpB, the gene encoding GBS C5a-ase. GBS strains with high C5a-ase functional
      activity and those with no or very low activity both express immunoreactive C5a
      ase. The scpB sequence of strain I30, which has high C5a-ase activity, is 98.2%
      homologous to the previously reported serotype II GBS scpB sequence. The scpB
      sequences of strains I25 and GW, which have low or no C5a-ase activity, are
      identical. The predicted I25 and GW C5a-ase proteins share a four-amino-acid
      deletion affecting the protease histidine active-site consensus motif.
      Recombinant I30 C5a-ase has good functional activity, whereas recombinant I25 C5a
      ase has low activity. These data demonstrate that functional C5a-ase differences
      between type III GBS strains are attributable to a genetic polymorphism of scpB.
      The ubiquitous expression of C5a-ase, irrespective of functional activity,
      suggests that C5a-ase may have a second, as yet unidentified, function.

PMID- 10948120
TI  - The major acute-phase protein, serum amyloid P component, in mice is not involved
      in endogenous resistance against tumor necrosis factor alpha-induced lethal
      hepatitis, shock, and skin necrosis.
AB  - The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) induces
      lethal hepatitis when injected into D-(+)-galactosamine-sensitized mice on the
      one hand or systemic inflammatory response syndrome (SIRS) in normal mice on the
      other hand. We studied whether serum amyloid P component (SAP), the major acute
      phase protein in mice, plays a protective role in both lethal models. For this
      purpose, we used SAP(0/0) mice generated by gene targeting. We studied the lethal
      response of SAP(0/0) or SAP(+/+) mice to both lethal triggers but found no
      differences in the sensitivity of both types of mice. We also investigated
      whether SAP is involved in establishing two types of endogenous protection: one
      using a single injection of interleukin-1beta (IL-1beta) for desensitization and
      clearly involving a liver protein, the other by tolerizing mice for 5 days using
      small doses of human TNF-alpha. Although after IL-1beta or after tolerization the
      SAP levels in the serum had risen fourfold in the control mice and not in the
      SAP(0/0) mice, the same extents of desensitization and tolerization were
      achieved. Finally, we observed that the induction of hemorrhagic necrosis in the
      skin of mice by two consecutive local injections with TNF-alpha was not altered
      in SAP(0/0) mice. We conclude that the presence or absence of SAP has no
      influence on the sensitivity of mice to TNF-alpha-induced hepatitis, SIRS, and
      hemorrhagic necrosis or on the endogenous protective mechanisms of
      desensitization or tolerization.

PMID- 10948121
TI  - Antigen detection in enteropathogenic Escherichia coli using secretory
      immunoglobulin A antibodies isolated from human breast milk.
AB  - Enteropathogenic Escherichia coli (EPEC) produces a characteristic attaching and
      effacing (A/E) lesion in the small intestines of infected children. The immune
      response to EPEC infection remains poorly characterized. The molecular targets
      that elicit protective immunity against EPEC disease are unknown. In this study
      protein antigens from EPEC were identified using secretory immunoglobulin A
      (sIgA) antibodies isolated from milk from Mexican women by Western blot analysis.
      Purified sIgA antibodies, which inhibit the adherence of EPEC to cells, reacted
      to many EPEC proteins, the most prominent of which were intimin (a 94-kDa outer
      membrane protein) and two unknown proteins with apparent molecular masses of 80
      and 70 kDa. A culture supernatant protein of 110 kDa also reacted strongly with
      the sIgA antibodies. The molecular size of this protein and its reactivity with
      specific anti-EspC antiserum suggest that it is EPEC-secreted protein C (EspC).
      These EPEC surface protein antigens were consistently recognized by all the
      different sIgA samples obtained from 15 women. Screening of clinical isolates of
      various O serogroups from cases of severe infantile diarrhea revealed that all
      EPEC strains able to produce the A/E lesion showed expression of intimin and the
      80- and 70-kDa proteins. Such proteins reacted strongly with the purified sIgA
      pool. Moreover, nonvirulent E. coli strains were unable to generate a sIgA
      response. The immunogenic capacities of the 80- and 70-kDa proteins as virulence
      antigens have not been previously reported. The strong sIgA response to intimin
      and the 80- and 70-kDa proteins obtained in this study indicates that such
      antigens stimulate intestinal immune responses and may elicit protective immunity
      against EPEC disease.

PMID- 10948122
TI  - Vibrio cholerae O139 conjugate vaccines: synthesis and immunogenicity of V.
      cholerae O139 capsular polysaccharide conjugates with recombinant diphtheria
      toxin mutant in mice.
AB  - Epidemiologic and experimental data provide evidence that a critical level of
      serum immunoglobulin G (IgG) antibodies to the surface polysaccharide of Vibrio
      cholerae O1 (lipopolysaccharide) and of Vibrio cholerae O139 (capsular
      polysaccharide [CPS]) is associated with immunity to the homologous pathogen. The
      immunogenicity of polysaccharides, especially in infants, may be enhanced by
      their covalent attachment to proteins (conjugates). Two synthetic schemes,
      involving 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-cyano-4
      dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents, were
      adapted to prepare four conjugates of V. cholerae O139 CPS with the recombinant
      diphtheria toxin mutant, CRMH21G. Adipic acid dihydrazide was used as a linker.
      When injected subcutaneously into young outbred mice by a clinically relevant
      dose and schedule, these conjugates elicited serum CPS antibodies of the IgG and
      IgM classes with vibriocidal activity to strains of capsulated V. cholerae O139.
      Treatment of these sera with 2-mercaptoethanol (2-ME) reduced, but did not
      eliminate, their vibriocidal activity. These results indicate that the conjugates
      elicited IgG with vibriocidal activity. Conjugates also elicited high levels of
      serum diphtheria toxin IgG. Convalescent sera from 20 cholera patients infected
      with V. cholerae O139 had vibriocidal titers ranging from 100 to 3,200:
      absorption with the CPS reduced the vibriocidal titer of all sera to < or =50.
      Treatment with 2-ME reduced the titers of 17 of 20 patients to < or =50. These
      data show that, like infection with V. cholerae O1, infection with V. cholerae
      O139 induces vibriocidal antibodies specific to the surface polysaccharide of
      this bacterium (CPS) that are mostly of IgM class. Based on these data, clinical
      trials with the V. cholerae O139 CPS conjugates with recombinant diphtheria toxin
      are planned.

PMID- 10948123
TI  - Purification of protease from a mixture of exfoliative toxin and newborn-mouse
      epidermis.
AB  - Although the role of exfoliative toxin in staphylococcal scalded-skin syndrome
      has been suggested to be that of a serine protease, it has not been demonstrated
      to show proteolytic activity. Our purpose was to purify a proteolytic enzyme from
      a mixture of exfoliative toxin and newborn-mouse epidermis. We used gel
      filtration and ion-exchange and hydroxyapatite chromatography with a high
      pressure liquid chromatography system. A casein-hydrolyzing enzyme was isolated
      from the mixture. The molecular mass of the enzyme was confirmed to be 20 kDa by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Subcutaneous injection
      of the purified enzyme into newborn mice reproduced the epidermal splitting that
      is seen in staphylococcal scalded-skin syndrome. These results suggest that
      exfoliative toxin does not work as a protease itself but that some reaction
      between exfoliative toxin and an epidermal component(s) first produces a
      protease, after which epidermal splitting occurs.

PMID- 10948124
TI  - Invasion genes are not required for Salmonella enterica serovar typhimurium to
      breach the intestinal epithelium: evidence that salmonella pathogenicity island 1
      has alternative functions during infection.
AB  - Salmonella enterica serovar Typhimurium invasion genes are necessary for
      bacterial invasion of intestinal epithelial cells and are thought to allow
      salmonellae to enter and cross the intestinal epithelium during infection. Many
      invasion genes are encoded on Salmonella pathogenicity island 1 (SPI1), and their
      expression is activated by HilA, a transcription factor also encoded on SPI1. We
      have studied the role of Salmonella invasion genes during infection of mice
      following intragastric inoculation. We have found that strains containing a
      mutation in hilA or invG were recovered from the intestinal contents, intestinal
      tissues, and systemic tissues at a lower frequency than their parental wild-type
      strain. In contrast, a strain in which SPI1 is deleted was recovered from
      infected mice at a frequency similar to that of its parental wild-type strain.
      The DeltaSPI1 phenotype indicates that S. enterica does not require invasion
      genes to cross the intestinal epithelium and infect systemic tissues. This result
      has forced us to reconsider the long-held belief that invasion genes directly
      mediate bacterial infection of the intestinal mucosa and traversion of the
      intestinal barrier during infection. Instead, our results suggest that hilA is
      required for bacterial colonization of the host intestine. The seemingly
      contradictory phenotype of the DeltaSPI1 mutant suggests that deletion of another
      gene(s) encoded on SPI1 suppresses the hilA mutant defect. We propose a model for
      S. enterica pathogenesis in which hilA and invasion genes are required for
      salmonellae to overcome a host clearance response elicited by another SPI1 gene
      product(s).

PMID- 10948125
TI  - Application of signature-tagged mutagenesis for identification of escherichia
      coli K1 genes that contribute to invasion of human brain microvascular
      endothelial cells.
AB  - Escherichia coli K1 is the leading cause of gram-negative bacterial meningitis in
      neonates. It is principally due to our limited understanding of the pathogenesis
      of this disease that the morbidity and mortality rates remain unacceptably high.
      To identify genes required for E. coli K1 penetration of the blood-brain barrier
      (BBB), we used the negative selection strategy of signature-tagged transposon
      mutagenesis (STM) to screen mutants for loss or decreased invasion of human brain
      microvascular endothelial cells (HBMEC) which comprise the BBB. A total of 3,360
      insertion mutants of E. coli K1 were screened, and potential HBMEC invasion
      mutants were subjected to a secondary invasion screen. Those mutants that failed
      to pass the serial invasion screens were then tested individually. Seven
      prototrophic mutants were found to exhibit significantly decreased invasive
      ability in HBMEC. We identified traJ and five previously uncharacterized loci
      whose gene products are necessary for HBMEC invasion by E. coli K1. In addition,
      cnf1, a gene previously shown to play a role in bacterial invasion, was
      identified. More importantly, a traJ mutant was attenuated in penetration of the
      BBB in the neonatal rat model of experimental hematogenous meningitis. This is
      the first in vivo demonstration that traJ is involved in the pathogenesis of E.
      coli K1 meningitis.

PMID- 10948126
TI  - Escherichia coli K1 aslA contributes to invasion of brain microvascular
      endothelial cells in vitro and in vivo.
AB  - Neonatal Escherichia coli meningitis remains a devastating disease, with
      unacceptably high morbidity and mortality despite advances in supportive care
      measures and bactericidal antibiotics. To further our ability to improve the
      outcome of affected neonates, a better understanding of the pathogenesis of the
      disease is necessary. To identify potential bacterial genes which contribute to
      E. coli invasion of the blood-brain barrier, a cerebrospinal fluid isolate of E.
      coli K1 was mutagenized with TnphoA. TnphoA mutant 27A-6 was found to have a
      significantly decreased ability to invade brain microvascular endothelial cells
      compared to the wild type. In vivo, 32% of the animals infected with mutant 27A-6
      developed meningitis, compared to 82% of those infected with the parent strain,
      despite similar levels of bacteremia. The DNA flanking the TnphoA insertion in
      27A-6 was cloned and sequenced and determined to be homologous to E. coli K-12
      aslA (arylsulfatase-like gene). The deduced amino acid sequence of the E. coli K1
      aslA gene product shows homology to a well-characterized arylsulfatase family of
      enzymes found in eukaryotes, as well as prokaryotes. Two additional aslA mutants
      were constructed by targeted gene disruption and internal gene deletion. Both of
      these mutants demonstrated decreased invasion phenotypes, similar to that of
      TnphoA mutant 27A-6. Complementation of the decreased-invasion phenotypes of
      these mutants was achieved when aslA was supplied in trans. This is the first
      demonstration that this locus contributes to invasion of the blood-brain barrier
      by E. coli K1.

PMID- 10948127
TI  - Fecal antibodies to Cryptosporidium parvum in healthy volunteers.
AB  - This study examined the intestinal antibody response in 26 healthy volunteers
      challenged with Cryptosporidium parvum oocysts. Fecal extracts were assayed for
      total secretory immunoglobulin A (IgA) and C. parvum-specific IgA reactivity.
      Specific IgA reactivity was standardized to IgA concentration and expressed as a
      reactivity index (RI). Anti-C. parvum fecal IgA (fIgA) increased significantly in
      17 of 26 (65.4%) following oocyst ingestion. Of those with detectable responses,
      59, 76.5, and 94.1% were positive by days 7, 14, and 30, respectively. Volunteers
      receiving high challenge doses (>1,000 and 300 to 500 oocysts) had higher RIs (RI
      = 5.57 [P = 0. 027] and RI = 1.68 [P = 0.039], respectively) than those ingesting
      low doses (30 to 100 oocysts; RI = 0.146). Subjects shedding oocysts and
      experiencing a diarrheal illness had the highest fIgA reactivity. When evaluated
      separately, oocyst excretion was associated with an increased fIgA response
      compared to nonshedders (RI = 1.679 versus 0. 024, respectively; P = 0.003).
      However, in subjects experiencing diarrhea with or without oocyst shedding, a
      trend toward a higher RI (P = 0.065) was seen. Extracts positive for fecal IgA
      were further examined for IgA subclass. The majority of stools contained both
      IgA1 and IgA2, and the relative proportions did not change following challenge.
      Also, no C. parvum-specific IgM or IgG was detected in fecal extracts. Thus,
      fecal IgA to C. parvum antigens was highly associated with infection in subjects
      who had no evidence of previous exposure and may provide a useful tool in
      detecting recent infections.

PMID- 10948130
TI  - Human response to Escherichia coli O157:H7 infection: antibodies to secreted
      virulence factors.
AB  - Vaccination has been proposed for the prevention of disease due to
      enterohemorrhagic Escherichia coli (EHEC), but the immune response following
      human infection, including the choice of potential antigens, has not been well
      characterized. To study this, sera were obtained from five pediatric patients
      with acute diarrhea caused by E. coli O157:H7 0, 8, and 60 days after
      hospitalization. These sera were used to examine the immune response to four
      different EHEC virulence factors: Tir (translocated intimin receptor, which is
      inserted into the host cell membrane), intimin (bacterial outer membrane protein
      which binds to Tir), EspA (secreted protein which forms filamentous structures on
      EHEC surface), and EspB (inserted into the host membrane and cytoplasm). The
      response to O157:H7 lipopolysaccharide was also examined. Sera were assayed
      against purified recombinant proteins using immunoblot analysis and by enzyme
      linked immunosorbent assay to determine the sera's titers to each of the antigens
      in all patients. We found that there was little reaction to EspA, EspB, and
      intimin in the acute-phase sera, although there was some reactivity to Tir. By
      day 8, titers of antibody to all four virulence factors were present in all
      patients, with a very strong response against Tir (up to a titer of 1:256,000),
      especially in hemolytic-uremic syndrome patients, and lesser strong responses to
      the other three antigens. The titer to the antigens 60 days after hospitalization
      was decreased but was still highest for Tir. These results suggest that there is
      a strong immune response to Tir, and to a lesser extent to the other three
      virulence factors, following EHEC disease, indicating that these bacterial
      molecules are potential vaccine candidates for preventing EHEC disease. They also
      suggest that bacterial virulence factors that are inserted into host cells during
      infection by type III secretion systems (Tir or EspB) are still recognized by the
      host immune response.

PMID- 10948128
TI  - Induction of colony-stimulating factor expression following Staphylococcus or
      Salmonella interaction with mouse or human osteoblasts.
AB  - Staphylococcus aureus and Salmonella spp. are common causes of bone diseases;
      however, the immune response during such infections is not well understood.
      Colony-stimulating factors (CSF) have a profound influence on osteoclastogenesis,
      as well as the development of immune responses following infection. Therefore, we
      questioned whether interaction of osteoblasts with two very different bacterial
      pathogens could affect CSF expression by these cells. Cultured mouse and human
      osteoblasts were exposed to various numbers of S. aureus or Salmonella dublin
      bacteria, and a comprehensive analysis of granulocyte-macrophage (GM)-CSF,
      granulocyte (G)-CSF, macrophage (M)-CSF, and interleukin-3 (IL-3) mRNA expression
      and cytokine secretion was performed. Expression of M-CSF and IL-3 mRNAs by mouse
      osteoblasts was constitutive and did not increase significantly following
      bacterial exposure. In contrast, GM-CSF and G-CSF mRNA expression by mouse
      osteoblasts was dramatically upregulated following interaction with either viable
      S. aureus or Salmonella. This increased mRNA expression also translated into high
      levels of GM-CSF and G-CSF secretion by mouse and human osteoblasts following
      bacterial exposure. Viable S. aureus and Salmonella induced maximal levels of CSF
      mRNA expression and cytokine secretion compared to UV-killed bacteria.
      Furthermore, GM-CSF and G-CSF mRNA expression could be induced in unexposed
      osteoblasts separated by a permeable Transwell membrane from bacterially exposed
      osteoblasts. M-CSF secretion was increased in cultures of exposed human
      osteoblasts but not in exposed mouse osteoblast cultures. Together, these studies
      are the first to define CSF expression and suggest that, following bacterial
      exposure, osteoblasts may influence osteoclastogenesis, as well as the
      development of an immune response, via the production of these cytokines.

PMID- 10948129
TI  - Differential expression of caveolin-1 in lipopolysaccharide-activated murine
      macrophages.
AB  - Five reciprocal cycles of subtractive hybridization using cDNA generated from
      fibroblasts with normal lipopolysaccharide (LPS) responsiveness (lps(n)) and from
      hyporesponsive (lps(d)) fibroblasts have led to the finding that caveolin-1 is
      expressed at markedly higher levels of mRNA in lps(d) than in lps(n) fibroblasts.
      Caveolin-1 message can also be readily detected via reverse transcription-PCR in
      the RAW264.7 and J774.1 macrophage-like cell lines as well as in primary
      thioglycolate (TG)-elicited mouse peritoneal macrophages. In RAW264.7 cells, both
      caveolin-1 mRNA and protein levels are down-regulated by LPS. In TG-elicited
      C3HeB/FeJ peritoneal macrophages, in contrast, expression of both caveolin-1
      protein and mRNA is up-regulated in vitro in response to LPS stimulation. The up
      regulation of caveolin-1 protein expression in C3HeB/FeJ peritoneal macrophages
      can be demonstrated at concentrations as low as 1.0 pg of LPS/ml. However, LPS
      concentrations approximately 4 orders of magnitude higher (10(4) pg/ml) were
      required to stimulate the LPS-hyporesponsive C3H/HeJ mice peritoneal macrophages
      such that significant caveolin-1 protein up-regulation was detected. Caveolin-1,
      a principal component of plasmalemmal caveolae, has been reported as a
      potentially important regulator for signal transduction during cellular
      stimulation. The results described in this report suggest that caveolin-1
      expression may be associated with LPS signaling/internalization.

PMID- 10948131
TI  - Construction and phenotypic evaluation of a Vibrio vulnificus vvpE mutant for
      elastolytic protease.
AB  - Vibrio vulnificus is an opportunistic gram-negative pathogen that commonly
      contaminates oysters. Predisposed individuals who consume raw oysters can die
      within days from sepsis, and even otherwise healthy people are susceptible to
      serious wound infection after contact with contaminated seafood or seawater.
      Numerous secreted and cell-associated virulence factors have been proposed to
      account for the fulminating and destructive nature of V. vulnificus infections.
      Among the putative virulence factors is an elastolytic metalloprotease. We cloned
      and sequenced the vvpE gene encoding an elastase of V. vulnificus ATCC 29307. The
      functions of the elastase were assessed by constructing vvpE insertional knockout
      mutants and evaluating phenotypic changes in vitro and in mice. Although other
      types of protease activity were still observed in vvpE mutants, elastase activity
      was completely absent in the mutants and was restored by reintroducing the
      recombinant vvpE gene. In contrast to previous characterization of elastase as a
      potential virulence factor, which was demonstrated by injecting the purified
      protein into animals, inactivation of the V. vulnificus vvpE gene did not affect
      the ability of the bacteria to infect mice and cause damage, either locally in
      subcutaneous tissues or systemically in the liver, in both iron-treated and
      normal mice. Furthermore, a vvpE mutant was not affected with regard to cytolytic
      activity toward INT407 epithelial cells or detachment of INT407 cells from
      culture dishes in vitro. Therefore, it appears that elastase is less important in
      the pathogenesis of V. vulnificus than would have been predicted by examining the
      effects of administering purified proteins to animals. However, V. vulnificus
      utilizes a variety of virulence factors; hence, the effects of inactivation of
      elastase alone could be masked by other compensatory virulence factors.

PMID- 10948132
TI  - Helicobacter hepaticus does not induce or potentiate colitis in interleukin-10
      deficient mice.
AB  - Helicobacter hepaticus has been reported to induce colitis, hepatitis, and
      hepatocellular carcinoma in several different murine models. The aim of this
      study was to determine if H. hepaticus will cause colitis in monoassociated mice
      lacking the interleukin-10 gene (IL-10(-/-) mice) and potentiate colitis in
      specific-pathogen-free (SPF) IL-10(-/-) mice. Germfree IL-10(-/-) mice on either
      a mixed (C57BL/6 x 129/Ola) or inbred (129/SvEv) genetic background were
      monoassociated with H. hepaticus ATCC 51448 by oral feeding and rectal enemas. In
      a second experiment, germfree IL-10(-/-) mice were colonized with stool from SPF
      mice that harbored or did not harbor endogenous H. hepaticus. After 7 to 9 weeks
      of colonization, weight loss and mortality were assessed, the colon was isolated
      for histology and IL-12 secretion, and mesenteric lymph node cells were assessed
      for T-cell activation markers. It was found that IL-10(-/-) mice monoassociated
      with H. hepaticus for up to 16 weeks showed almost no histologic colitis or
      increased IL-12 production. SPF IL-10-knockout mice had no significant difference
      in weight loss, mortality rate, histologic scores, colonic IL-12 secretion, or T
      cell activation with or without H. hepaticus. We conclude that H. hepaticus does
      not induce or potentiate disease in our IL-10(-/-) mice and therefore is not
      required to induce colitis in genetically susceptible hosts.

PMID- 10948133
TI  - Modulation of cardiocyte functional activity by antibodies against trypanosoma
      cruzi ribosomal P2 protein C terminus.
AB  - Antibodies against the Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) have
      been associated with the chronic cardiac pathology of Chagas' disease in humans.
      Using synthetic peptides spanning the entire TcP2beta molecule, we investigated
      their epitope recognition by antibodies from mice chronically infected with T.
      cruzi and from mice immunized with two recombinant TcP2betas. We found clear
      differences in epitope recognition between antibodies from T. cruzi-infected mice
      and mice immunized with two different recombinant TcP2betas associated with
      different schedules of immunization. Major epitopes recognized by antibodies from
      mice immunized with recombinant glutathione S-transferase (GST) or histidine
      (Hist) fusion TcP2beta (GST-TcP2beta or Hist-TcP2beta) are located in the central
      and hinge regions of the molecule. Nevertheless, mice immunized with Hist
      TcP2beta were also able to elicit antibodies against the TcP2beta C terminus, a
      region which is highly conserved in both T. cruzi and mammal ribosomal P
      proteins. Strikingly, antibodies from infected animals recognized only the
      TcP2beta C terminus. By using these antisera with distinct profiles of epitope
      recognition, it could be shown that only C terminus-specific antibodies were able
      to increase the beating frequency of cardiomyocytes from neonatal rats in vitro
      by selective stimulation of the beta1-adrenergic receptor. Thus, antibodies
      against the TcP2beta C terminus elicited in the absence of infection are able to
      modulate a functional activity of host cells through a molecular mimicry
      mechanism.

PMID- 10948134
TI  - Enhancement of neonatal innate defense: effects of adding an N-terminal
      recombinant fragment of bactericidal/permeability-increasing protein on growth
      and tumor necrosis factor-inducing activity of gram-negative bacteria tested in
      neonatal cord blood ex vivo.
AB  - Innate defense against microbial infection requires the action of neutrophils,
      which have cytoplasmic granules replete with antibiotic proteins and peptides.
      Bactericidal/permeability-increasing protein (BPI) is found in the primary
      granules of adult neutrophils, has a high affinity for lipopolysaccharides (or
      "endotoxins"), and exerts selective cytotoxic, antiendotoxic, and opsonic
      activity against gram-negative bacteria. We have previously reported that
      neutrophils derived from newborn cord blood are deficient in BPI (O. Levy et al.,
      Pediatrics 104:1327-1333, 1999). The relative deficiency in BPI of newborns
      raised the possibility that supplementing the levels of BPI in plasma might
      enhance newborn antibacterial defense. Here we determined the effects of addition
      of recombinant 21-kDa N-terminal BPI fragment (rBPI(21)) on the growth and tumor
      necrosis factor (TNF)-inducing activity of representative gram-negative clinical
      isolates. Bacteria were tested in citrated newborn cord blood or adult peripheral
      blood. Bacterial viability was assessed by plating assay, and TNF-alpha release
      was measured by enzyme-linked immunosorbent assay. Whereas adult blood limited
      the growth of all isolates except Klebsiella pneumoniae, cord blood also allowed
      logarithmic growth of Escherichia coli K1/r and Citrobacter koseri. Bacteria
      varied in their susceptibility to rBPI(21)'s bactericidal action: E. coli K1/r
      was relatively susceptible (50% inhibitory concentration [IC(50)], approximately
      10 nM), C. koseri was intermediate (IC(50), approximately 1,000 nM), Klebsiella
      pneumoniae was resistant (IC(50), approximately 10,000 nM), and Enterobacter
      cloacae and Serratia marcescens were highly resistant (IC(50), >10,000 nM). All
      isolates were potent inducers of TNF-alpha activity in both adult and newborn
      cord blood. In contrast to its variable antibacterial activity, rBPI(21)
      consistently inhibited the TNF-inducing activity of all strains tested (IC(50), 1
      to 1,000 nM). The antibacterial effects of rBPI(21) were additive with those of a
      combination of conventional antibiotics typically used to treat bacteremic
      newborns (ampicillin and gentamicin). Whereas ampicillin and gentamicin
      demonstrated little inhibition of bacterially induced TNF release, addition of
      rBPI(21) either alone or together with ampicillin and gentamicin profoundly
      inhibited release of this cytokine. Thus, supplementing newborn cord blood with
      rBPI(21) potently inhibited the TNF-inducing activity of a variety of gram
      negative bacterial clinical pathogens and, in some cases, enhanced bactericidal
      activity. These results suggest that administration of rBPI(21) may be of
      clinical benefit to neonates suffering from gram-negative bacterial infection
      and/or endotoxemia.

PMID- 10948136
TI  - A novel factor isolated from Actinobacillus actinomycetemcomitans stimulates
      mouse B cells and human peripheral blood mononuclear cells.
AB  - A novel immunostimulating factor (ISTF) of Actinobacillus actinomycetemcomitans
      ATCC 29522 was isolated and characterized as inducing proliferation of mouse B
      cells and human peripheral blood mononuclear cells. This factor was isolated from
      the bacterial culture medium and purified by size exclusion chromatography, dye
      ligand affinity chromatography, immunoaffinity chromatography using monoclonal
      antibodies, and preparative electrophoresis. Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed that the purified ISTF migrated as a
      single band corresponding to a molecular mass of 13 kDa. ISTF was a proteinaceous
      material distinct from lipopolysaccharide; it directly induced the proliferation
      of B lymphocytes but had no effect on the proliferation of T lymphocytes, even in
      the presence of antigen-presenting cells. A B-lymphocyte-mitogenic activity of
      ISTF was also shown by flow cytometric analysis of responding cell
      subpopulations. Immunoblot analysis revealed that ISTF was a component of the
      outer membranes of bacteria, could exist as a soluble form, and was released by
      growing and/or lysed bacteria. These results suggest that ISTF produced by A.
      actinomycetemcomitans may play an important role in immunopathologic changes
      associated with A. actinomycetemcomitans infections.

PMID- 10948135
TI  - Interleukin 18 restores defective Th1 immunity to Candida albicans in caspase 1
      deficient mice.
AB  - Caspase 1, formerly designated interleukin 1beta (IL-1beta)-converting enzyme,
      processes pro-IL-1beta and pro-IL-18 to yield active cytokines that play a
      pivotal role in inflammation and cell activation. We show here the effect of
      caspase 1 deficiency on the inflammatory and adaptive immune responses to the
      fungus Candida albicans. Caspase 1 deficiency did not affect susceptibility to
      primary systemic infection with the fungus, as revealed by survival and fungal
      growth. However, Th1-mediated resistance to reinfection was greatly impaired in
      caspase 1-deficient mice, and this correlated with low-level production of IL-12
      and gamma interferon. Early in infection, production of these cytokines and that
      of tumor necrosis factor alpha, IL-6, and, interestingly, IL-1beta occurred
      normally in caspase 1-deficient mice, while that of IL-18 was severely impaired.
      Exogenous administration of IL-18, more than IL-12, restored the Th1-mediated
      resistance to the infection. We conclude that, while caspase 1 is not
      indispensable for release of mature IL-1beta in candidiasis, the caspase 1
      dependent production of IL-18 may represent an important and novel pathway for
      the expression of sustained Th1 reactivity to the fungus.

PMID- 10948137
TI  - Babesia bovis-stimulated macrophages express interleukin-1beta, interleukin-12,
      tumor necrosis factor alpha, and nitric oxide and inhibit parasite replication in
      vitro.
AB  - The tick-transmitted hemoparasite Babesia bovis causes an acute infection that
      results in persistence and immunity against challenge infection in cattle that
      control the initial parasitemia. Resolution of acute infection with this
      protozoal pathogen is believed to be dependent on products of activated
      macrophages (Mphi), including inflammatory cytokines and nitric oxide (NO) and
      its derivatives. B. bovis stimulates inducible nitric oxide synthase (iNOS) and
      production of NO in bovine Mphi, and chemical donors of NO inhibit the growth of
      B. bovis in vitro. However, the induction of inflammatory cytokines in Mphi by
      babesial parasites has not been described, and the antiparasitic activity of NO
      produced by B. bovis-stimulated Mphi has not been definitively demonstrated. We
      report that monocyte-derived Mphi activated by B. bovis expressed enhanced levels
      of inflammatory cytokines interleukin-1beta (IL-1beta), IL-12, and tumor necrosis
      factor alpha that are important for stimulating innate and acquired immunity
      against protozoal pathogens. Furthermore, a lipid fraction of B. bovis-infected
      erythrocytes stimulated iNOS expression and NO production by Mphi. Cocultures of
      Mphi and B. bovis-infected erythrocytes either in contact or physically separated
      resulted in reduced parasite viability. However, NO produced by bovine Mphi in
      response to B. bovis-infected erythrocytes was only partially responsible for
      parasite growth inhibition, suggesting that additional factors contribute to the
      inhibition of B. bovis replication. These findings demonstrate that B. bovis
      induces an innate immune response that is capable of controlling parasite
      replication and that could potentially result in host survival and parasite
      persistence.

PMID- 10948138
TI  - Regulation of cytokine expression in mice immunized with cryptococcal
      polysaccharide, a glucuronoxylomannan (GXM), associated with peritoneal antigen
      presenting cells (APC): requirements for GXM, APC activation, and interleukin-12.
AB  - Mice immunized with peritoneal exudate cells (PEC; used as antigen-presenting
      cells [APC]) that are pulsed ex vivo with cryptococcal capsular polysaccharide, a
      glucuronoxylomannan (GXM), exhibit increased survival times and delayed-type
      hypersensitivity reactions when they are infected with Cryptococcus neoformans.
      These responses are GXM specific. The present study revealed that GXM-APC
      immunization enhanced development of anticryptococcal type-1 cytokine responses
      (interleukin-2 [IL-2] and gamma interferon) in mice infected with C. neoformans.
      The enhancement was not GXM specific, because immunization with GXM-APC and
      immunization with APC alone had similar effects. GXM-APC (or APC) immunization
      caused small increases in the expression of type-2 cytokines (IL-4 and IL-5), but
      the increases were not always statistically significant. IL-10 levels were not
      regulated by immunization with GXM-APC or APC. GXM-APC prepared with PEC
      harvested from mice injected with complete Freund's adjuvant (CFA) enhanced type
      1 cytokine responses, while GXM-APC prepared with PEC induced with incomplete
      Freund's adjuvant were ineffective. The CFA-induced PEC had an activated
      phenotype characterized by increased numbers of F4/80(+) cells that expressed
      CD40, B7-1, and B7-2 on their membranes. The immunomodulatory activity of the CFA
      induced APC population was not attributed to their production of IL-12 because
      GXM-APC prepared with peritoneal cells harvested from IL-12 knockout mice or
      their wild-type counterparts were equally effective in augmenting the type-1
      response. Blocking of IL-12 in the recipients of GXM-APC early after APC infusion
      revealed that early induction of IL-12 secretion was not responsible for the
      immunomodulatory response elicited by GXM-APC. These data, considered together
      with previously reported data, reveal that the protective activity of GXM-APC
      immunization involves both antigen-specific and nonspecific activities of GXM
      APC.

PMID- 10948139
TI  - Mycobacterium tuberculosis and Legionella pneumophila phagosomes exhibit arrested
      maturation despite acquisition of Rab7.
AB  - Rab7 is a small GTPase that regulates vesicular traffic from early to late
      endosomal stages of the endocytic pathway. Phagosomes containing inert particles
      have also been shown to transiently acquire Rab7 as they mature. Disruption in
      the pathway prior to the acquisition of Rab7 has been suggested as playing a role
      in the altered maturation of Mycobacterium bovis BCG phagosomes. As a first step
      to determine whether disruption in the delivery or function of Rab7 could play a
      role in the altered maturation of Legionella pneumophila and M. tuberculosis
      phagosomes, we have examined the distribution of wild-type Rab7 and the GTPase
      deficient, constitutively active mutant form of Rab7 in HeLa cells infected with
      L. pneumophila or M. tuberculosis. We have found that the majority of L.
      pneumophila and M. tuberculosis phagosomes acquire relatively abundant staining
      for Rab7 and for the constitutively active mutant Rab7 in HeLa cells that
      overexpress these proteins. Nevertheless, despite acquisition of wild-type or
      constitutively active Rab7, both the L. pneumophila and the M. tuberculosis
      phagosomes continue to exhibit altered maturation as manifested by a failure to
      acquire lysosome-associated membrane glycoprotein 1. These results demonstrate
      that L. pneumophila and M. tuberculosis phagosomes have receptors for Rab7 and
      that the altered maturation of these phagosomes is not due to a failure to
      acquire Rab7.

PMID- 10948141
TI  - Evolution of lesion formation, parasitic load, immune response, and reservoir
      potential in C57BL/6 mice following high- and low-dose challenge with Leishmania
      major.
AB  - A model of cutaneous leishmaniasis using 10(2) Leishmania major metacyclic
      promastigotes inoculated into the footpads of genetically resistant C57BL/6 mice
      was studied in order to more accurately reproduce the evolution of lesion
      formation and the kinetics of parasite growth and immune response as they might
      occur in naturally exposed reservoirs and in human hosts. In contrast to the more
      conventional experimental model employing 10(6) metacyclic promastigotes, in
      which the rapid development of footpad lesions was associated with an increasing
      number of amastigotes in the site, the low-dose model revealed a remarkably
      "silent" phase of parasite growth, lasting approximately 6 weeks, during which
      peak parasitic loads were established in the absence of any overt pathology.
      Footpad swelling was observed after 6 weeks, coincident with the onset of
      parasite clearance and with production of high levels of interleukin-12 (IL-12)
      and gamma interferon (IFN-gamma) in draining lymph nodes. Low-dose challenge of
      IL-12- and IFN-gamma-depleted or -deficient mice provided strong evidence that
      the induction or expression of cellular immunity is essentially absent during the
      first 6 to 8 weeks of intracellular growth, since the concentration of
      amastigotes in the site was not enhanced compared to that for wild-type animals
      during this time. By monitoring the ability of infected mice to transmit
      parasites to vector sand flies, it was observed that following low-dose
      challenge, footpads without apparent lesions provided an efficient source of
      parasites for exposed flies and that the low-dose challenge actually extended the
      duration of parasite transmissibility during the course of infection.

PMID- 10948140
TI  - Mediation of Cryptosporidium parvum infection in vitro by mucin-like
      glycoproteins defined by a neutralizing monoclonal antibody.
AB  - The protozoan parasite Cryptosporidium parvum is a significant cause of diarrheal
      disease worldwide. Attachment to and invasion of host intestinal epithelial cells
      by C. parvum sporozoites are crucial steps in the pathogenesis of
      cryptosporidiosis. The molecular basis of these initial interactions is unknown.
      In order to identify putative C. parvum adhesion- and invasion-specific proteins,
      we raised monoclonal antibodies (MAbs) to sporozoites and evaluated them for
      inhibition of attachment and invasion in vitro. Using this approach, we
      identified two glycoproteins recognized by 4E9, a MAb which neutralized C. parvum
      infection and inhibited sporozoite attachment to intestinal epithelial cells in
      vitro. 4E9 recognized a 40-kDa glycoprotein named gp40 and a second, >220-kDa
      protein which was identified as GP900, a previously described mucin-like
      glycoprotein. Glycoproteins recognized by 4E9 are localized to the surface and
      apical region of invasive stages and are shed in trails from the parasite during
      gliding motility. The epitope recognized by 4E9 contains alpha-N
      acetylgalactosamine residues, which are present in a mucin-type O-glycosidic
      linkage. Lectins specific for these glycans bind to the surface and apical region
      of sporozoites and block attachment to host cells. The surface and apical
      localization of these glycoproteins and the neutralizing effect of the MAb and
      alpha-N-acetylgalactosamine-specific lectins strongly implicate these proteins
      and their glycotopes as playing a role in C. parvum-host cell interactions.

PMID- 10948142
TI  - Shiga toxin-induced tumor necrosis factor alpha expression: requirement for toxin
      enzymatic activity and monocyte protein kinase C and protein tyrosine kinases.
AB  - Infections with Shiga toxin (Stx)-producing bacteria cause bloody diarrhea which
      may progress to life-threatening complications, including acute renal failure and
      neurological abnormalities. The precise mechanism of disease progression is
      unclear, although evidence suggests that the localized production of the host
      proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin
      1 may exacerbate toxin-mediated vascular damage. Purified Stxs have been
      demonstrated to elicit proinflammatory cytokine synthesis from human peripheral
      blood mononuclear cells and monocytic cell lines in vitro. To understand toxin
      monocyte interactions required for cytokine synthesis, we have treated
      differentiated THP-1 cells with purified wild-type toxins, enzymatic mutants, or
      B subunits and measured TNF-alpha production. Our data suggest that A subunit
      enzymatic activity is essential for cytokine production. THP-1 cells were treated
      with a series of protein kinase C (PKC), PKA, and protein tyrosine kinase
      inhibitors to examine the role of intracellular signaling molecules in Stx
      mediated cytokine production. Treatment of cells with PKC and tyrosine kinase
      inhibitors blocked TNF-alpha secretion by Stx-stimulated THP-1 cells. Stx
      treatment directly activated PKC, which occurred at a point upstream of
      transcriptional activation of the gene encoding TNF-alpha.

PMID- 10948143
TI  - T-cell-independent responses to Borrelia burgdorferi are critical for protective
      immunity and resolution of lyme disease.
AB  - The humoral immune response to Borrelia burgdorferi during persistent infection
      is critical to both protective and disease-resolving immunity. This study
      examined the role of B cells in the absence of T cells during these events, using
      mice with selected immune dysfunctions. At 6 weeks postinfection, an interval at
      which arthritis resolves in immunocompetent mice, arthritis severity was
      equivalent among immunocompetent mice, alphabeta(+)-T-cell-deficient mice, and
      mice lacking both alphabeta(+) and gammadelta(+) T cells. Arthritis severity was
      worse in SCID mice, which lack T and B lymphocytes. Carditis regressed in
      immunocompetent mice and those lacking both alphabeta(+) and gammadelta(+) T
      cells but remained active in mice lacking only alphabeta(+) T cells and in SCID
      mice. Mice lacking only alphabeta(+) T cells and those lacking both alphabeta(+)
      and gammadelta(+) T cells generated immunoglobulin M (IgM) and IgG3 B.
      burgdorferi-reactive antibodies. Sera from infected immunocompetent mice, mice
      lacking only alphabeta(+) T cells, and mice lacking both alphabeta(+) and
      gammadelta(+) T cells passively protected naive mice against challenge
      inoculation with B. burgdorferi. However, only sera from infected immunocompetent
      mice, but not sera from infected T-cell-deficient mice, were able to resolve
      arthritis when passively transferred to actively infected SCID mice. These data
      demonstrate that B-cell activation during a T-cell-independent response may be
      critical for resolution of arthritis and carditis and that protective antibodies
      are generated during this response.

PMID- 10948144
TI  - Cytokine responses to Plasmodium falciparum liver-stage antigen 1 vary in rainy
      and dry seasons in highland Kenya.
AB  - Seasonal epidemics of malaria occur in highland areas of western Kenya where
      transmission intensity varies according to rainfall. This study describes the
      seasonal changes in cytokine responses to Plasmodium falciparum liver-stage
      antigen 1 (LSA-1) by children (< or =17 years old) and adults (> or =18 years
      old) living in such a highland area. Fourteen- to 24-mer peptides corresponding
      to the N- and C-terminal nonrepeat regions of LSA-1 stimulated production of
      interleukin-5 (IL-5), interleukin-10 (IL-10), gamma interferon (IFN-gamma), and
      tumor necrosis factor alpha (TNF-alpha) by peripheral blood mononuclear cells
      (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10
      and TNF-alpha responses were more frequent during the high-transmission, rainy
      season than during the low-transmission, dry season (73 and 67% versus 17 and 25%
      response rates, respectively). In contrast, there was no seasonal change in the
      proportion of LSA-1-driven IFN-gamma and IL-5 responses. Children produced less
      IFN-gamma than adults, but IL-5, IL-10, and TNF-alpha levels were similar for
      both age groups. Depletion of CD8(+) cells from PBMC decreased IFN-gamma but
      increased IL-10 production. Individuals with LSA-1-stimulated IL-10 responses in
      the dry season were less likely to become reinfected in the subsequent rainy
      season than those without IL-10 responses (25% versus 49%; P = 0.083). These data
      support the notion that maintenance of LSA-1-driven IL-10 and TNF-alpha responses
      requires repeated and sustained exposure to liver-stage P. falciparum. In
      contrast, IFN-gamma responses increase slowly with age but persist once acquired.
      CD8(+) T cells are the major source of IFN-gamma but may suppress production or
      secretion of IL-10.

PMID- 10948145
TI  - Production of toxic shock syndrome toxin 1 by Staphylococcus aureus requires both
      oxygen and carbon dioxide.
AB  - The effect of O(2) and CO(2) on expression of toxic shock syndrome toxin 1 (TSST
      1) by Staphylococcus aureus was investigated under controlled growth conditions
      with continuous-culture techniques. To stimulate TSST-1 production, air and
      anaerobic gas were premixed before delivery to the culture vessel. At a growth
      rate-or mass doubling time (t(d))-of 3 h, production of specific TSST-1
      (expressed as micrograms per milligram of cell dry weight) was 5. 9-fold greater
      at an O(2) concentration of 4% than under anaerobic conditions. Increasing the
      O(2) concentration to 11% did not result in a significant increase (P> 0.05) in
      the rate of toxin production over that during growth in 4% O(2) but did result in
      a significant increase (4.9-fold; P<0.001) in the rate of toxin production over
      that during anaerobic growth. At a t(d) of 9 h, addition of 3.5% O(2) resulted in
      a 7.6-fold increase in specific TSST-1 production. When room air was sparged
      through a culture growing at a t(d) of 9 h, TSST-1 production increased
      significantly (by 3.4-fold) over that during anaerobic growth. When a growth
      environment of 4% O(2)-remainder N(2) was studied, no increase in TSST-1
      production was observed; this was also the case with 8% O(2) at gas-flow rates of
      0.1, 0.2, and 0.4 liters/min. In all experiments, production of biomass
      (expressed as milligrams of cell dry weight per milliliter) increased, indicating
      that O(2) was metabolized by S. aureus. Addition of CO(2) to the gas mix (4%
      O(2), 10% CO(2), 86% N(2)) resulted in a 5.1- to 6.8-fold increase in TSST-1
      production over that during anaerobic growth and a 3.6-fold increase over that
      during growth in an environment of 4% O(2)-remainder N(2). The agr mutant strain
      tested produced 6.1-fold more specific TSST-1 in a growth environment of 4% O(2)
      10% CO(2)-86% N(2) than during anaerobic growth. These data suggest that in this
      system, O(2) alone does not trigger production of TSST-1; rather, both CO(2) and
      O(2) are required.

PMID- 10948146
TI  - Diversity of ace, a gene encoding a microbial surface component recognizing
      adhesive matrix molecules, from different strains of Enterococcus faecalis and
      evidence for production of ace during human infections.
AB  - Our previous work reported that most Enterococcus faecalis strains adhered to the
      extracellular matrix proteins collagen types I and IV and laminin after growth at
      46 degrees C, but not 37 degrees C, and we subsequently identified an E. faecalis
      sequence, ace, that encodes a bacterial adhesin similar to the collagen binding
      protein Cna of Staphylococcus aureus. In this study, we examined the diversity of
      E. faecalis-specific ace gene sequences among different isolates obtained from
      various geographic regions as well as from various clinical sources. A comparison
      of nucleotide and deduced amino acid sequences of Ace from nine E. faecalis
      strains identified a highly conserved N-terminal A domain, followed by a variable
      B domain which contains two to five repeats of 47 amino acids in tandem array,
      preceded by a 20-amino-acid partial repeat. Using 17 other strains collected
      worldwide, the 5' region of ace that encodes the A domain was sequenced, and
      these sequences showed > or =97.5% identity. Among the previously reported five
      amino acids critical for collagen binding by Cna of S. aureus, four were found to
      be identical in Ace from all strains tested. Polyclonal immune rabbit serum
      prepared against recombinant Ace A derived from E. faecalis strain OG1RF detected
      Ace in mutanolysin extracts of seven of nine E. faecalis strains after growth at
      46 degrees C; Ace was detected in four different molecular sizes that correspond
      to the variation in the B repeat region. To determine if there was any evidence
      to indicate that Ace might be produced under physiological conditions, we
      quantitatively assayed sera collected from patients with enterococcal infections
      for the presence of anti-Ace A antibodies. Ninety percent of sera (19 of 21) from
      patients with E. faecalis endocarditis showed reactivity with titers from 1:32 to
      >1:1,024; the only 2 sera which lacked antibodies to Ace A had considerably lower
      titers of antibodies to other E. faecalis antigens as well. Human-derived, anti
      Ace A immunoglobulins G purified from an E. faecalis endocarditis patient serum
      inhibited adherence of 46 degrees C-grown E. faecalis OG1RF to collagen types I
      and IV and laminin. In conclusion, these results show that ace is highly
      conserved among isolates of E. faecalis, with at least four variants related to
      the differences in the B domain, is expressed by different strains during
      infection in humans, and human-derived antibodies can block adherence to these
      extracellular matrix proteins.

PMID- 10948147
TI  - Enterococcus faecalis adhesin, ace, mediates attachment to extracellular matrix
      proteins collagen type IV and laminin as well as collagen type I.
AB  - Adhesin-mediated binding to extracellular matrix (ECM) proteins is thought to be
      a crucial step in the pathogenic process of many bacterial infections. We have
      previously reported conditional adherence of most Enterococcus faecalis isolates,
      after growth at 46 degrees C, to ECM proteins collagen types I and IV and
      laminin; identified an E. faecalis-specific gene, ace, whose encoded protein has
      characteristics of a bacterial adhesin; and implicated Ace in binding to collagen
      type I. In this study, we constructed an ace disruption mutant from E. faecalis
      strain OG1RF that showed marked reduction in adherence to collagen types I and IV
      and laminin when compared to the parental OG1RF strain after growth at 46 degrees
      C. Polyclonal immune serum raised against the OG1RF-derived recombinant Ace A
      domain reacted with a single approximately 105-kDa band of mutanolysin extracts
      from OG1RF grown at 46 degrees C, while no band was detected in extracts from
      OG1RF grown at 37 degrees C, nor from the OG1RF ace mutant grown at 37 or 46
      degrees C. IgGs purified from the anti-Ace A immune serum inhibited adherence of
      46 degrees C-grown E. faecalis OG1RF to immobilized collagen type IV and laminin
      as well as collagen type I, at a concentration as low as 1 microg/ml, and also
      inhibited the 46 degrees C-evoked adherence of two clinical isolates tested. We
      also showed in vitro interaction of collagen type IV with Ace from OG1RF
      mutanolysin extracts on a far-Western blot. Binding of recombinant Ace A to
      immobilized collagen types I and IV and laminin was demonstrated in an enzyme
      linked immunosorbent assay and was shown to be concentration dependent. These
      results indicate that Ace A mediates the conditional binding of E. faecalis OG1RF
      to collagen type IV and laminin in addition to collagen type I.

PMID- 10948148
TI  - Effect of Helicobacter pylori on polymorphonuclear leukocyte migration across
      polarized T84 epithelial cell monolayers: role of vacuolating toxin VacA and cag
      pathogenicity island.
AB  - Helicobacter pylori infection can induce polymorphonuclear leukocyte (PMNL)
      infiltration of the gastric mucosa, which characterizes acute chronic gastritis.
      The mechanisms underlying this process are poorly documented. The lack of an in
      vitro model has considerably impaired the study of transepithelial migration of
      PMNL induced by H. pylori. In the present work, we used confluent polarized
      monolayers of the human intestinal cell line T84 grown on permeable filters to
      analyze the epithelial PMNL response induced by broth culture filtrates (BCFs)
      and bacterial suspensions from different strains of H. pylori. We have evaluated
      the role of the vacuolating cytotoxin VacA and of the cag pathogenicity island
      (PAI) of H. pylori in PMNL migration via their effects on T84 epithelial cells.
      We noted no difference in the rates of PMNL transepithelial migration after
      epithelial preincubation with bacterial suspensions or with BCFs of VacA-negative
      or VacA-positive H. pylori strains. In contrast, PMNL transepithelial migration
      was induced after incubation of the T84 cells with cag PAI-positive and cagE
      positive H. pylori strains. Finally, PMNL migration was correlated with a
      basolateral secretion of interleukin-8 by T84 cells, thus creating a
      subepithelial chemotactic gradient for PMNL. These data provide evidence that the
      vacuolating cytotoxin VacA is not involved in PMNL transepithelial migration and
      that the cag PAI, with a pivotal role for the cagE gene, provokes a transcellular
      signal across T84 monolayers, inducing a subepithelial PMNL response.

PMID- 10948149
TI  - Induction of interleukin-4 (IL-4) by legionella pneumophila infection in BALB/c
      mice and regulation of tumor necrosis factor alpha, IL-6, and IL-1beta.
AB  - Infection of BALB/c mice with a sublethal concentration of Legionella pneumophila
      causes an acute disease that is resolved by innate immune responses. The
      infection also initiates the development of adaptive Th1 responses that protect
      the mice from challenge infections. To study the early responses, cytokines
      induced during the first 24 h after infection were examined. In the serum,
      interleukin-12 (IL-12) was detectable by 3 h and peaked at 10 h, while gamma
      interferon was discernible by 5 h and peaked at 8 h. Similar patterns were
      observed in ex vivo cultures of splenocytes. A transient IL-4 response was also
      detected by 3 h postinfection in ex vivo cultures. BALB/c IL-4-deficient mice
      were more susceptible to L. pneumophila infection than were wild-type mice. The
      infection induced higher serum levels of acute-phase cytokines (tumor necrosis
      factor alpha [TNF-alpha], IL-1beta, and IL-6), and reducing TNF-alpha levels with
      antibodies protected the mice from death. Moreover, the addition of IL-4 to L.
      pneumophila-infected macrophage cultures suppressed the production of these
      cytokines. Thus, the lack of IL-4 in the deficient mice resulted in unchecked TNF
      alpha production, which appeared to cause the mortality. Monocyte chemoattractant
      protein-1 (MCP-1), a chemokine that is induced by IL-4 during Listeria
      monocytogenes infection, was detected at between 2 and 30 h after infection.
      However, MCP-1 did not appear to be induced by IL-4 or to be required for the TNF
      alpha regulation by IL-4. The data suggest that the early increase in IL-4 serves
      to regulate the mobilization of acute phase cytokines and thus controls the
      potential harmful effects of these cytokines.

PMID- 10948150
TI  - Gonococcal nitric oxide reductase is encoded by a single gene, norB, which is
      required for anaerobic growth and is induced by nitric oxide.
AB  - The gene encoding a nitric oxide reductase has been identified in Neisseria
      gonorrhoeae. The norB gene product shares significant identity with the nitric
      oxide reductases in Ralstonia eutropha and Synechocystis sp. and, like those
      organisms, the gonococcus lacks a norC homolog. The gonococcal norB gene was
      found to be required for anaerobic growth, but the absence of norB did not
      dramatically decrease anaerobic survival. In a wild-type background, induction of
      norB expression was seen anaerobically in the presence of nitrite but not
      anaerobically without nitrite or aerobically. norB expression is not regulated by
      FNR or NarP, but a functional aniA gene (which encodes an anaerobically induced
      outer membrane nitrite reductase) is necessary for expression. When aniA is
      constitutively expressed, norB expression can be induced both anaerobically and
      aerobically, but only in the presence of nitrite, suggesting that nitric oxide,
      which is likely to be produced by AniA as a product of nitrite reduction, is the
      inducing agent. This was confirmed with the use of the nitric oxide donor,
      spermine-nitric oxide complex, in an aniA null background both anaerobically and
      aerobically. NorB is important for gonococcal adaptation to an anaerobic
      environment, a physiologically relevant state during gonococcal infection. The
      presence of this enzyme, which is induced by nitric oxide, may also have
      implications in immune evasion and immunomodulation in the human host.

PMID- 10948151
TI  - Characterization of Porphyromonas gingivalis insertion sequence-like element
      ISPg5.
AB  - Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is found in
      periodontitis lesions, and its presence in subgingival plaque significantly
      increases the risk for periodontitis. In contrast to many bacterial pathogens, P.
      gingivalis strains display considerable variability, which is likely due to
      genetic exchange and intragenomic changes. To explore the latter possibility, we
      have studied the occurrence of insertion sequence (IS)-like elements in P.
      gingivalis W83 by utilizing a convenient and rapid method of capturing IS-like
      sequences and through analysis of the genome sequence of P. gingivalis strain
      W83. We adapted the method of Matsutani et al. (S. Matsutani, H. Ohtsubo, Y.
      Maeda, and E. Ohtsubo, J. Mol. Biol. 196:445-455, 1987) to isolate and clone
      rapidly annealing DNA sequences characteristic of repetitive regions within a
      genome. We show that in P. gingivalis strain W83, such sequences include (i)
      nucleotide sequence with homology to tRNA genes, (ii) a previously described IS
      element, and (iii) a novel IS-like element. Analysis of the P. gingivalis genome
      sequence for the distribution of the least used tetranucleotide, CTAG, identified
      regions in many of the initial 218 contigs which contained CTAG clusters.
      Examination of these CTAG clusters led to the discovery of 11 copies of the same
      novel IS-like element identified by the repeated sequence capture method of
      Matsutani et al. This new 1,512-bp IS-like element, designated ISPg5, has
      features of the IS3 family of IS elements. When a recombinant plasmid containing
      much of ISPg5 was used in Southern analysis of several P. gingivalis strains,
      including clinical isolates, diversity among strains was apparent. This suggests
      that ISPg5 and other IS elements may contribute to strain diversity and can be
      used for strain fingerprinting.

PMID- 10948152
TI  - Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan:
      structural requirements differ from those for responses to lipopolysaccharide.
AB  - The purpose of this study was to identify the functional significance of the
      binding of soluble CD14 (sCD14) to bacterial peptidoglycan (PGN) and to compare
      the structural requirements of sCD14 for the binding to PGN and
      lipopolysaccharide (LPS) and for sCD14-mediated enhancement of PGN- and LPS
      induced cell responses. sCD14 did not facilitate the responses of membrane CD14
      (mCD14)-negative pre-B 70Z/3 cells to PGN, although it facilitated the responses
      of these cells to LPS and although mCD14 facilitated the responses of 70Z/3 cells
      to PGN. sCD14 enhanced mCD14-mediated cell activation by both PGN and LPS, but
      only the responses to LPS, and not to PGN, were enhanced by LPS-binding protein.
      Four 4- or 5-amino-acid-long sequences within the 65-amino-acid N-terminal region
      of sCD14 were needed for binding to both PGN and LPS and for enhancement of cell
      activation by both PGN and LPS. However, deletions of individual sequences had
      different effects on the ability of sCD14 to bind to PGN and to LPS and on the
      ability to enhance the responses to PGN and to LPS. Thus, there are different
      structural requirements of sCD14 for binding to PGN and to LPS and for the
      enhancement of PGN- and LPS-induced cell activation.

PMID- 10948153
TI  - Lipooligosaccharide P(k) (Galalpha1-4Galbeta1-4Glc) epitope of moraxella
      catarrhalis is a factor in resistance to bactericidal activity mediated by normal
      human serum.
AB  - Moraxella catarrhalis is a respiratory pathogen responsible for acute bacterial
      otitis media in children and exacerbation of chronic bronchitis in adults. M.
      catarrhalis strains are frequently resistant to the bactericidal activity of
      normal human serum. In order to determine if the lipooligosaccharide (LOS) of M.
      catarrhalis has a role in serum resistance, the UDP-glucose-4-epimerase (galE)
      gene was identified, cloned, and sequenced and a deletion/insertion mutation was
      introduced into M. catarrhalis strain 2951. GalE enzymatic activity, measured in
      whole-cell lysates, was ablated in M. catarrhalis 2951 galE. Mass spectrometric
      analysis of LOS isolated with hot phenol-water confirmed that strain 2951
      produced a type A LOS. These studies showed that the LOS from 2951 galE had lost
      two hexose residues due to the galE mutation and that the resultant LOS structure
      lacked the (Galalpha1-4Galbeta1-4Glc) P(k) epitope found on M. catarrhalis 2951.
      Wild-type M. catarrhalis 2951 is resistant to complement-mediated serum
      bactericidal activity. In contrast, a greater than 2-log(10)-unit reduction in
      CFU occurred after incubation of 2951 galE in either 50 or 25% pooled human serum
      (PNHS), and CFU in 10% PNHS decreased by about 1 log(10) unit. These studies
      suggest that the P(k) epitope of the LOS may be an important factor in the
      resistance of M. catarrhalis to the complement-mediated bactericidal effect of
      normal human serum.

PMID- 10948154
TI  - Evidence for contribution of tripartite hemolysin BL, phosphatidylcholine
      preferring phospholipase C, and collagenase to virulence of Bacillus cereus
      endophthalmitis.
AB  - Bacillus cereus causes a highly fulminant endophthalmitis which usually results
      in blindness. We previously concluded that hemolysin BL (HBL), a tripartite
      necrotizing pore-forming toxin, is a probable endophthalmitis virulence factor
      because it is highly toxic to retinal tissue in vitro and in vivo. We also
      determined that B. cereus produces additional retinal toxins that might
      contribute to virulence. Here we fractionated crude B. cereus culture supernatant
      by anion-exchange chromatography and found that in vitro retinal toxicity was
      also associated with phosphatidylcholine-preferring phospholipase C (PC-PLC). The
      pure enzyme also caused retinal necrosis in vivo. We showed that
      phosphatidylinositol-specific PLC and sphingomyelinase were nontoxic and that two
      hemolysins, cereolysin O and a novel hemolysin designated hemolysin IV, were
      marginally toxic in vitro. The histopathology of experimental septic
      endophthalmitis in rabbits mimicked the pathology produced by pure HBL, and both
      HBL and PC-PLC were detected at toxic concentrations in infected vitreous fluid.
      Bacterial cells were first seen associated with the posterior margin of the lens
      and eventually were located throughout the lens cortex. Detection of collagenase
      in the vitreous humor suggested that infiltration was facilitated by the
      breakdown of the protective collagen lens capsule by that enzyme. This work
      supports our conclusion that HBL contributes to B. cereus virulence and
      implicates PC-PLC and collagenase as additional virulence factors.

PMID- 10948155
TI  - ankA: an Ehrlichia phagocytophila group gene encoding a cytoplasmic protein
      antigen with ankyrin repeats.
AB  - Human granulocytic ehrlichiosis (HGE) is a potentially fatal, tick-borne disease
      caused by a bacterium related or identical to Ehrlichia phagocytophila. To
      identify and characterize E. phagocytophila group-specific protein antigen genes,
      we prepared and screened HGE agent and Ehrlichia equi genomic DNA expression
      libraries using polyclonal equine E. equi antibodies. Two clones, one each from
      HGE agent and E. equi, that were recognized specifically by antibodies to the E.
      phagocytophila group ehrlichiae had complete open reading frames of 3,693 and
      3,615 nucleotides, respectively. The two clones were 96.6% identical and
      predicted a protein with at least 11 tandemly repeated ankyrin motifs. Thus, the
      gene was named ank (for ankyrin). When the encoded protein, named AnkA, was
      expressed in Escherichia coli, it was recognized by antibodies from rabbits and
      mice immunized with the HGE agent, sera from humans convalescent from HGE, and
      sera from horses convalescent from HGE and E. equi infection. Monospecific AnkA
      antibodies reacted with proteins in HGE agent immunoblots, and AnkA monoclonal
      antibodies detected cytoplasmic antigen in E. phagocytophila group bacteria and
      also detected antigen associated with chromatin in infected but not uninfected HL
      60 cell cultures. These results suggest that this Ehrlichia protein may influence
      host cell gene expression.

PMID- 10948156
TI  - Cytokine responses to treponema pectinovorum and treponema denticola in human
      gingival fibroblasts.
AB  - Human gingival fibroblasts were challenged with Treponema pectinovorum and
      Treponema denticola to test three specific hypotheses: (i) these treponemes
      induce different cytokine profiles from the fibroblasts, (ii) differences in
      cytokine profiles are observed after challenge with live versus killed
      treponemes, and (iii) differences in cytokine profiles are noted from different
      gingival fibroblast cell lines when challenged with these treponemes. Three
      normal gingival fibroblast cell cultures were challenged with T. pectinovorum and
      T. denticola strains, and the supernatants were analyzed for cytokine production
      (i.e., interleukin-1alpha [IL-1alpha], IL-1beta, IL-6, IL-8, IL-10, gamma
      interferon, macrophage chemotactic protein 1 [MCP-1], platelet-derived growth
      factor, tumor necrosis factor alpha, and granulocyte-macrophage colony
      stimulating factor). Unstimulated fibroblast cell lines produced IL-6, IL-8, and
      MCP-1. T. pectinovorum routinely elicited the greatest production of these
      cytokines from the fibroblast cell lines, increasing 10- to 50-fold over basal
      production. While T. denticola also induced IL-6 and IL-8 production, these
      levels were generally lower than those elicited by challenge with T.
      pectinovorum. MCP-1 levels were significantly lower after T. denticola challenge,
      and the kinetics suggested that this microorganism actually inhibited basal
      production by the fibroblasts. No basal or stimulated production of the other
      cytokines was observed. Significant differences were noted in the responsiveness
      of the various cell lines with respect to the two species of treponemes and the
      individual cytokines produced. Finally, dead T. pectinovorum generally induced a
      twofold-greater level of IL-6 and IL-8 than the live bacteria. These results
      supported the idea that different species of oral treponemes can elicit
      proinflammatory cytokine production by gingival cells and that this stimulation
      did not require live microorganisms. Importantly, a unique difference was noted
      in the ability of T. pectinovorum to induce a robust MCP-1 production, while T.
      denticola appeared to inhibit this activity of the fibroblasts. While the general
      cytokine profiles of the fibroblast cell cultures were similar, significant
      differences were noted in the quantity of individual cytokines produced, which
      could relate to individual patient variation in local inflammatory responses in
      the periodontium.

PMID- 10948157
TI  - Characterization of lymphocyte response in the female genital tract during
      ascending Chlamydial genital infection in the guinea pig model.
AB  - It is well known that pathology caused by chlamydial infection is associated
      closely with the host response to the organism and that both innate and adaptive
      host responses contribute to tissue damage. While it is likely that the organism
      itself initiates the acute inflammatory response by eliciting cytokine and
      chemokine production from the host cell, the adaptive response is the result of
      activation of the cell-mediated immune response. While there are several studies
      describing the nature of the pathologic response in primate, guinea pig, and
      murine models, there is less information on the kinetics of the CD4 and CD8
      response following primary and challenge infections. In this study, we have
      quantified by flow cytometry the mononuclear cell response to genital infection
      with the agent of guinea pig inclusion conjunctivitis in the cervix, endometrium,
      and oviducts at various times following a primary intravaginal infection and
      after a challenge infection. Tissues from individual animals were assessed for
      cells expressing CD4, CD8, or Mac-1 and for B cells. Peak responses of each
      subset occurred 10 to 14 days after a primary infection. The number of Mac-1
      expressing cells in each tissue site was found to be dependent on the size of the
      inoculating dose of chlamydiae. The responses of each cell type were generally
      stronger in the cervix than in the upper genital tract. In contrast to the murine
      model but consistent with the primate models, there were equal numbers of CD4 and
      CD8 cells present in the infiltrates. Twenty-one days after challenge infection,
      which was performed 50 days after the primary infection, there was a significant
      increase in the number of CD4, CD8, and B cells in the oviduct compared to the
      number of these cells at the same time after a primary infection, providing clear
      cellular evidence for a cell-mediated immune pathologic response.

PMID- 10948159
TI  - Transcutaneous immunization with bacterial ADP-ribosylating exotoxins, subunits,
      and unrelated adjuvants.
AB  - We have recently described a needle-free method of vaccination, transcutaneous
      immunization, consisting of the topical application of vaccine antigens to intact
      skin. While most proteins themselves are poor immunogens on the skin, we have
      shown that the addition of cholera toxin (CT), a mucosal adjuvant, results in
      cellular and humoral immune responses to the adjuvant and coadministered
      antigens. The present study explores the breadth of adjuvants that have activity
      on the skin, using diphtheria toxoid (DTx) and tetanus toxoid as model antigens.
      Heat-labile enterotoxin (LT) displayed adjuvant properties similar to those of CT
      when used on the skin and induced protective immune responses against tetanus
      toxin challenge when applied topically at doses as low as 1 microg.
      Interestingly, enterotoxin derivatives LTR192G, LTK63, and LTR72 and the
      recombinant CT B subunit also exhibited adjuvant properties on the skin.
      Consistent with the latter finding, non-ADP-ribosylating exotoxins, including an
      oligonucleotide DNA sequence, as well as several cytokines (interleukin-1beta [IL
      1beta] fragment, IL-2, IL-12, and tumor necrosis factor alpha) and
      lipopolysaccharide also elicited detectable anti-DTx immunoglobulin G titers in
      the immunized mice. These results indicate that enhancement of the immune
      response to topical immunization is not restricted to CT or the ADP-ribosylating
      exotoxins as adjuvants. This study also reinforces earlier findings that addition
      of an adjuvant is important for the induction of robust immune responses to
      vaccine antigens delivered by topical application.

PMID- 10948158
TI  - Does inhibition of tumor necrosis factor alpha affect chlamydial genital tract
      infection in mice and guinea pigs?
AB  - The role of tumor necrosis factor alpha (TNF-alpha) in host defense against
      chlamydial infection remains unclear. In order to further evaluate the relevance
      of TNF-alpha to host resistance in chlamydial genital tract infection, we
      examined the effect of local inhibition of the TNF-alpha response in normal C57
      mice and in interferon gamma gene-deficient C57 mice infected intravaginally with
      the mouse pneumonitis agent of Chlamydia trachomatis. Since the guinea pig model
      of female genital tract infection more closely approximates the human in terms of
      ascending infection and development of pathology, we also examined the effect of
      local inhibition of the TNF-alpha response in guinea pigs infected intravaginally
      with the guinea pig strain of Chlamydia psittaci. We successfully blocked the
      early TNF-alpha response in the respective animal models. This blockade had no
      effect on the numbers of organisms isolated from the genital tract during the
      time of TNF-alpha inhibition in mice or guinea pigs. Analysis of interleukin
      1beta, macrophage inflammatory protein-2, and granulocyte macrophage-colony
      stimulating factor in the mouse model revealed that blockade of the TNF-alpha
      response did not alter the release of these proinflammatory proteins. Yet, in TNF
      alpha-depleted mice, increased numbers of neutrophils were detected in the
      genital tract, and, in TNF-alpha-depleted guinea pigs, increased numbers of
      neutrophils as well as infiltrating lymphocytes were seen in the endocervix.
      Blockade of TNF-alpha does not affect the level of infection in mice or guinea
      pigs, but it may decrease TNF-alpha-induced apoptosis of infiltrating
      inflammatory cells.

PMID- 10948160
TI  - Impaired control of Brucella melitensis infection in Rag1-deficient mice.
AB  - After intranasal inoculation, Brucella melitensis chronically infects the
      mononuclear phagocyte system in BALB/c mice, but it causes no apparent illness.
      Adaptive immunity, which can be transferred by either T cells or antibody from
      immune to naive animals, confers resistance to challenge infection. The role of
      innate, non-B-, non-T-cell-mediated immunity in control of murine brucellosis,
      however, is unknown. In the present study, we documented that BALB/c and C57BL/6
      mice had a similar course of infection after intranasal administration of 16M,
      validating the usefulness of the model in the latter mouse strain. We then
      compared the course of infection in Rag1 knockout mice (C57BL/6 background)
      (referred to here as RAG-1 mice) which have no B or T cells as a consequence of
      deletion of Rag1 (recombination-activating gene 1), with infection in normal
      C57BL/6 animals after intranasal administration of B. melitensis 16M. C57BL/6
      mice cleared brucellae from their lungs by 8 to 12 weeks and controlled infection
      in the liver and spleen at a low level. In contrast, RAG-1 mice failed to reduce
      the number of bacteria in any of these organs. From 1 to 4 weeks after
      inoculation, the number of splenic bacteria increased from 2 to 4.5 logs and
      remained at that level. In contrast to the consistently high numbers of brucellae
      observed in the spleens, the number of bacteria rose in the livers sampled for up
      to 20 weeks. Immunohistologic examination at 8 weeks after infection disclosed
      foci of persistent pneumonia and large amounts of Brucella antigen in macrophages
      in lung, liver, and spleen in RAG-1, but not C57BL/6, mice. These studies
      indicate that T- and B-cell-independent immunity can control Brucella infection
      at a high level in the murine spleen, but not in the liver. Immunity mediated by
      T and/or B cells is required for clearance of bacteria from spleen and lung and
      for control of bacterial replication in the liver.

PMID- 10948161
TI  - Chronic Helicobacter pylori infection induces an apoptosis-resistant phenotype
      associated with decreased expression of p27(kip1).
AB  - Helicobacter pylori infection is associated with the development of gastric
      cancer. In short-term coculture with AGS gastric cells, H. pylori inhibits cell
      cycle progression and induces dose-dependent apoptosis. Based on the concept that
      an imbalance between proliferation and apoptosis may contribute to the emergence
      of gastric cancer, we chronically exposed AGS cells to H. pylori as a model of
      chronic exposure in humans. The AGS derivatives selected by this process were
      stably resistant not only to H. pylori-induced apoptosis but also to apoptosis
      induced by other enteric bacteria and by several toxic agents including radiation
      and cancer chemotherapy. Like the parental AGS cells, the derivatives underwent
      G(1)/S-phase cell cycle inhibition in response to H. pylori. The AGS derivatives
      displayed a marked decrease in cellular levels of the cell cycle control protein
      p27(kip1). We found a similar decrease in epithelial cell p27(kip1) expression in
      gastric biopsy specimens from H. pylori-infected patients. These findings are
      consistent with observations that link decreases in the p27(kip1) level to
      increased susceptibility to cancer in mice with p27(kip1) deleted and to a poor
      prognosis of gastric cancer in humans. This is the first demonstration that
      bacterial infection can lead to apoptosis resistance and to cross-resistance to
      other inducers of apoptosis such as bacteria, chemotherapeutic agents, and
      radiation. The development of apoptosis resistance and downmodulation of
      p27(kip1) may contribute to the increased risk for gastric cancer observed in
      humans chronically exposed to H. pylori.

PMID- 10948162
TI  - Suppression of macrophage activation with CNI-1493 increases survival in infant
      rats with systemic Haemophilus influenzae infection.
AB  - CNI-1493, a potent macrophage deactivator, was used to treat infant rats
      systemically infected with Haemophilus influenzae type b (Hib). CNI-1493 was
      injected 1 h prior to bacterial inoculation and 24 h later and resulted in a 75
      percent increased rate of survival compared to that for untreated controls. The
      effect of CNI-1493 on the inflammatory response was studied by
      immunohistochemical detection of individual tumor necrosis factor alpha (TNF
      alpha)-, interleukin 1 beta (IL-1beta)-, and gamma interferon (IFN-gamma)
      producing cells in the spleen. A significant reduction of the incidence of TNF
      alpha- and IL-1beta-expressing cells was found for CNI-1493-treated animals. IFN
      gamma expression was not suppressed by CNI-1493, indicating that cytokine
      inhibition was specific in macrophages. CNI-1493 significantly reduced the number
      of infiltrating granulocytes in the brain from that for controls. This study
      provides evidence that CNI-1493 protects against lethal Hib infection by
      deactivating the inflammatory cascade in infant rats.

PMID- 10948163
TI  - Apically exposed, tight junction-associated beta1-integrins allow binding and
      YopE-mediated perturbation of epithelial barriers by wild-type Yersinia bacteria.
AB  - Using polarized epithelial cells, primarily MDCK-1, we assessed the mode of
      binding and effects on epithelial cell structure and permeability of Yersinia
      pseudotuberculosis yadA-deficient mutants. Initially, all bacteria except the
      invasin-deficient (inv) mutant adhered apically to the tight junction areas.
      These contact points of adjacent cells displayed beta1-integrins together with
      tight junction-associated ZO-1 and occludin proteins. Indeed, beta1-integrin
      expression was maximal in the tight junction area and then gradually decreased
      along the basolateral membranes. Wild-type bacteria also opened gradually the
      tight junction to paracellular permeation of different-sized markers, viz., 20-,
      40-, and 70-kDa dextrans and 45-kDa ovalbumin, as well as to their own
      translocation between adjacent cells in intimate contact with beta1-integrins.
      The effects on the epithelial cells and their barrier properties could primarily
      be attributed to expression of the Yersinia outer membrane protein YopE, as the
      yopE mutant bound but caused no cytotoxicity. Moreover, the apical structure of
      filamentous actin (F-actin) was disturbed and tight junction-associated proteins
      (ZO-1 and occludin) were dispersed along the basolateral membranes. It is
      concluded that the Yersinia bacteria attach to beta1-integrins at tight
      junctions. Via this localized injection of YopE, they perturb the F-actin
      structure and distribution of proteins forming and regulating tight junctions.
      Thereby they promote paracellular translocation of bacteria and soluble
      compounds.

PMID- 10948164
TI  - Up-regulation of both intimin and eae-independent adherence of shiga toxigenic
      Escherichia coli O157 by ler and phenotypic impact of a naturally occurring ler
      mutation.
AB  - Shiga toxigenic Escherichia coli (STEC) strains are important human pathogens
      which are capable of causing diarrhea, hemorrhagic colitis, and the potentially
      fatal hemolytic-uremic syndrome (HUS). An important virulence trait of certain
      STEC strains, such as those belonging to serogroup O157, is the capacity to
      produce attaching and effacing (A/E) lesions on enterocytes, a property encoded
      by the locus for enterocyte effacement (LEE). LEE contains the eae gene, which
      encodes intimin, an outer membrane protein which mediates the intimate attachment
      of bacteria to the host epithelial cell surface, and eae is routinely used as a
      marker for LEE-positive STEC strains. However, the O157:H(-) STEC strain 95SF2
      carries eae but did not produce A/E lesions on HEp-2 cells, as judged by a
      fluorescent actin staining assay. In this assay, 95SF2 adhered poorly to the HEp
      2 cells, and those that did bind exhibited abnormal cell division. In contrast,
      the O157:H7 STEC strain EDL933 adhered strongly and produced typical A/E lesions.
      We have demonstrated that 95SF2 carries a defective LEE regulatory gene, ler,
      with a single base change with respect to that published for ler of EDL933,
      resulting in an Ile(57)-to-Thr substitution. Ler shows homology to H-NS-like
      regulators, which are modulators of transcription, and the mutation occurs in a
      domain implicated in oligomerization. 95SF2 was able to adhere and produce A/E
      lesions on HEp-2 cells when EDL933 ler was expressed from a multicopy plasmid.
      Conversely, introduction of a plasmid carrying 95SF2 ler into EDL933 abolished
      adherence and capacity to form A/E lesions. Studies with eae deletion derivatives
      of 95SF2 and EDL933 demonstrated that the ler-mediated adherence to HEp-2 cells
      is largely independent of intimin. We have also demonstrated that EDL933 ler, but
      not 95SF2 ler, increases the level of intimin in O157 STEC.

PMID- 10948166
TI  - Immunopathology of cerebral malaria: morphological evidence of parasite
      sequestration in murine brain microvasculature.
AB  - A murine model that closely resembles human cerebral malaria is presented, in
      which characteristic features of parasite sequestration and inflammation in the
      brain are clearly demonstrable. "Young" (BALB/c x C57BL/6)F(1) mice infected with
      Plasmodium berghei (ANKA) developed typical neurological symptoms 7 to 8 days
      later and then died, although their parasitemias were below 20%. Older animals
      were less susceptible. Immunohistopathology and ultrastructure demonstrated that
      neurological symptoms were associated with sequestration of both parasitized
      erythrocytes and leukocytes and with clogging and rupture of vessels in both
      cerebral and cerebellar regions. Increases in tumor necrosis factor alpha and
      CD54 expression were also present. Similar phenomena were absent or substantially
      reduced in older infected but asymptomatic animals. These findings suggest that
      this murine model is suitable both for determining precise pathogenetic features
      of the cerebral form of the disease and for evaluating circumventive
      interventions.

PMID- 10948165
TI  - Neisseria gonorrhoeae elicits membrane ruffling and cytoskeletal rearrangements
      upon infection of primary human endocervical and ectocervical cells.
AB  - Neisseria gonorrhoeae is a strict human pathogen that is, primarily, transmitted
      by close sexual contact with an infected individual. Gonococcal infection of the
      male urogenital tract has been well studied in experimental human models and in
      urethral cell culture systems. Recent studies, using tissue culture cell systems,
      have suggested a role for the cervical epithelium in gonococcal infection of
      females; however, the nature of gonococcal infection of the normal uterine cervix
      remains controversial. To address this enigma, we have developed two primary
      human cervical epithelial cell systems from surgical biopsies. Gonococcal
      infection studies and electron microscopy show that N. gonorrhoeae is capable of
      infecting and invading both the endo- and the ectocervix. Invasion was found to
      occur primarily in an actin-dependent manner, but it does not appear to require
      de novo protein synthesis by either the bacterium or the host cervical cell.
      Membrane ruffles appear to be induced in response to gonococci. Consistent with
      membrane ruffling, gonococci were found residing within macropinosomes, and a
      concentrated accumulation of actin-associated proteins was observed to occur in
      response to gonococcal infection. Electron microscopy of clinically derived
      cervical biopsies show that lamellipodia formation and cytoskeletal changes,
      suggestive of membrane ruffles, also occur in the cervical epithelium of women
      with naturally acquired gonococcal cervicitis. These studies demonstrate the
      ability of N. gonorrhoeae to infect and invade both the endo- and the ectocervix
      of the normal uterine cervix. Gonococcal induced ruffling is a novel finding and
      may be unique to the cervical epithelium.

PMID- 10948167
TI  - Burkholderia pseudomallei induces cell fusion and actin-associated membrane
      protrusion: a possible mechanism for cell-to-cell spreading.
AB  - Burkholderia pseudomallei, a facultative intracellular bacterium, is the
      causative agent of a broad spectrum of diseases collectively known as
      melioidosis. Its ability to survive inside phagocytic and nonphagocytic cells and
      to induce multinucleated giant cell (MNGC) formation has been demonstrated. This
      study was designed to assess a possible mechanism(s) leading to this cellular
      change, using virulent and nonvirulent strains of B. pseudomallei to infect both
      phagocytic and nonphagocytic cell lines. We demonstrated that when the cells were
      labeled with two different cell markers (CMFDA or CMTMR), mixed, and then
      infected with B. pseudomallei, direct cell-to-cell fusion could be observed,
      leading to MNGC formation. Staining of the infected cells with rhodamine
      conjugated phalloidin indicated that immediately after the infection, actin
      rearrangement into a comet tail appearance occurred, similar to that described
      earlier for other bacteria. The latter rearrangement led to the formation of
      bacterium-containing, actin-associated membrane protrusions which could lead to a
      direct cell-to-cell spreading of B. pseudomallei in the infected hosts. Results
      from 4', 6'-diamidine-2-phenylindole dihydrochloride (DAPI) nuclear staining,
      poly-ADP ribose polymerase cleavage, staining of infected cells for
      phosphatidylserine exposure with annexin V, and electrophoresis of the DNA
      extracted from these infected cells showed that B. pseudomallei could kill the
      host cells by inducing apoptosis in both phagocytic and nonphagocytic cells.

PMID- 10948168
TI  - Staphylococcus aureus RN6390 replicates and induces apoptosis in a pulmonary
      epithelial cell line.
AB  - Staphylococcus aureus frequently colonizes the airways of patients with
      compromised airway defenses (e.g., cystic fibrosis [CF] patients) for extended
      periods. Persistent and relapsing infections may be related to live S. aureus
      bacteria actively residing inside epithelial cells. In this study, we infected a
      respiratory epithelial cell line, which was derived from a CF patient, with S.
      aureus RN6390. Internalization of S. aureus was found to be time and dose
      dependent and could be blocked by cytochalasin D. Transmission electron
      microscopy revealed that internalized bacteria resided within endocytic vacuoles
      without any evidence of lysosomal fusion in a 24-h period. The results of
      internalization experiments and time-lapse fluorescence microscopy of epithelial
      cells infected with green fluorescent S. aureus indicate that, after an initial
      lag period of 7 to 9 h, intracellular bacteria began to replicate, with three to
      five divisions in a 24-h period, leading to apoptosis of infected cells.
      Induction of apoptosis required bacterial internalization and is associated with
      intracellular replication. The slow and gradual replication of S. aureus inside
      epithelial cells hints at the role of host factors or signals in bacterial growth
      and further suggests possible cross talk between host cells and S. aureus.

PMID- 10948169
TI  - Distinct response kinetics of gamma interferon and interleukin-4 in bovine
      tuberculosis.
AB  - This study shows that gamma interferon (IFN-gamma) and interleukin-4 (IL-4)
      cytokine responses are produced by peripheral blood cells in cattle infected with
      Mycobacterium bovis. The different kinetics of the IFN-gamma and IL-4 responses
      to bovine tuberculin and to ESAT-6 following experimental intratracheal infection
      with M. bovis are described. An early increase in IFN-gamma was observed that was
      maintained throughout the period studied. In contrast, the IL-4 response was
      delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly,
      an experimental challenge of cattle with a lower dose of M. bovis which did not
      result in the development of lesions, positive DTH skin test, or substantial IFN
      gamma responses nevertheless generated strong specific IL-4 responses.
      Investigation of naturally infected M. bovis field reactors showed increased IFN
      gamma and IL-4 responses compared to uninfected cattle and that both of these
      cytokines were equally able to differentiate infected from uninfected animals.
      The magnitude of the M. bovis-induced IL-4 responses were found to be similar to
      the antigen-specific IL-4 responses of cattle infected with the parasitic
      nematode Onchocerca ochengi, further supporting the presence of this type 2
      cytokine in bovine tuberculosis.

PMID- 10948170
TI  - Vacuole acidification is not required for survival of Salmonella enterica serovar
      typhimurium within cultured macrophages and epithelial cells.
AB  - Phagosome acidification is an important component of the microbicidal response by
      infected eukaryotic cells. Thus, intracellular pathogens that reside within
      phagosomes must either block phagosome acidification or be able to survive at low
      pH. In this work, we studied the effect of phagosomal acidification on the
      survival of intracellular Salmonella enterica serovar Typhimurium in different
      cell types. Bafilomycin A1, a specific inhibitor of the vacuolar proton-ATPases,
      was used to block acidification of salmonella-containing vacuoles. We found that
      in several epithelial cell lines, treatment with bafilomycin A1 had no effect on
      intracellular survival or replication. Furthermore, although acidification was
      essential for Salmonella intracellular survival in J774 cultured macrophages, as
      reported previously (13), it is not essential in other macrophage cell lines.
      These data suggest that vacuolar acidification may play a role in intracellular
      survival of salmonellae only under certain conditions and in specific cell types.

PMID- 10948171
TI  - Transforming growth factor beta1 is expressed in the jejunum after experimental
      Cryptosporidium parvum infection in humans.
AB  - Biopsies from volunteers challenged with Cryptosporidium parvum were examined for
      transforming growth factor beta1 (TGF-beta1). None of the prechallenge biopsies
      exhibited TGF-beta. Seven of 12 volunteers with oocyst shedding expressed TGF
      beta versus 2 of 13 volunteers without detected oocysts. The association of TGF
      beta expression with oocyst excretion and the timing of symptoms suggests that
      TGF-beta mediates intestinal healing.

PMID- 10948172
TI  - Uptake and killing of Leptospira interrogans and Borrelia burgdorferi,
      spirochetes pathogenic to humans, by reticuloendothelial cells in perfused rat
      liver.
AB  - In situ-perfused rat livers were infused with a single dose of 1.5 x 10(7)
      radiolabeled cells of Leptospira interrogans serovar icterohaemorrhagiae, the
      agent of leptospirosis, or with Borrelia burgdorferi IRS, the agent of Lyme
      disease. Significant (P<0.0001) differences in the liver uptake of L. interrogans
      and of B. burgdorferi were observed, the uptakes being 37.4%+/-2.3% for L.
      interrogans and 60.5%+/-3.1% for B. burgdorferi. Leptospires, in contrast to
      borreliae, were recovered from the livers when liver samples were cultured in
      growth medium. Leptospires but not borreliae were recovered in bile within 30 min
      of infusion. The association of leptospires and borreliae with
      reticuloendothelial cells of the liver was demonstrated by immunohistochemistry.
      Leptospires and borreliae were found to be associated with vimentin-positive
      cells and not with desmin-positive cells. Few leptospires but no borreliae were
      also seen associated with vimentin- and desmin-negative cells, suggesting the
      presence of leptospires outside the sinusoidal spaces, in the liver parenchyma.

PMID- 10948173
TI  - Regulation of human beta-defensins by gastric epithelial cells in response to
      infection with Helicobacter pylori or stimulation with interleukin-1.
AB  - Gastric epithelial cells in vitro and in vivo are shown to constitutively express
      the peptide antibiotic human beta-defensin type 1 (hBD-1). In contrast, hBD-2
      expression is regulated in gastric epithelial cells and increases in response to
      infection with Helicobacter pylori or stimulation with the proinflammatory
      cytokine interleukin-1. These data suggest that hBD-2 is a component of the
      regulated host gastric epithelial cell response to H. pylori infection and
      proinflammatory mediators.

PMID- 10948174
TI  - Invasion of human vascular endothelial cells by Actinobacillus
      actinomycetemcomitans via the receptor for platelet-activating factor.
AB  - Strains of the periodontal pathogen Actinobacillus actinomycetemcomitans are
      variable with respect to display of phosphorylcholine (PC)-bearing antigens. We
      have examined strains of A. actinomycetemcomitans with and without PC to assess
      their ability to invade endothelial cells via the receptor for platelet
      activating factor (PAF). Results of antibiotic protection assays indicate that PC
      bearing A. actinomycetemcomitans invade human vascular endothelial cells by a
      mechanism inhibitable by CV3988, a PAF receptor antagonist, and by PAF itself.
      The invasive phenotype was verified by transmission electron microscopy. A PC
      deficient strain of this organism was not invasive. This property, in addition to
      the established ability of A. actinomycetemcomitans to invade epithelial cells,
      may provide this organism with access to the systemic circulation. The ability of
      PC-bearing oral bacteria to access the circulation may also explain the elevated
      levels of anti-PC antibody in serum found in patients with periodontitis.

PMID- 10948175
TI  - Prevotella intermedia stimulates expansion of Vbeta-specific CD4(+) T cells.
AB  - Recent evidence suggests that certain periodontal pathogens preferentially
      stimulate T cells expressing specific variable regions on the beta chain (Vbeta)
      of the T-cell receptor, which may indicate the presence of a superantigen.
      Superantigens are microbial proteins that activate large numbers of CD4(+) T
      cells in a Vbeta-specific manner. The purpose of this study was to determine
      whether Prevotella intermedia, a putative periodontal pathogen, activates
      populations of specific Vbeta on CD4(+) T cells. Among the bacterial strains
      tested, P. intermedia strain 17, a clinical isolate, induced the strongest
      proliferative response in peripheral blood mononuclear cells. Antibodies raised
      against whole cells of this organism blocked the proliferative activity. P.
      intermedia-induced proliferation was T-cell specific and required the presence of
      antigen-presenting cells. Flow cytometric analysis showed that CD4(+) T-cell
      subsets expressing Vbeta8, Vbeta12, and Vbeta17 expanded in response to P.
      intermedia strain 17. The ability of P. intermedia to stimulate CD4(+)-T-cell
      proliferation was further supported by the production profiles of key T-cell
      cytokines, gamma interferon and interleukin-2. The data collectively suggest that
      certain strains of P. intermedia can activate Vbeta-specific T cells in a manner
      similar to that of other known microbial superantigens.

PMID- 10948176
TI  - Possible release of an ArgGlyArgProGln pentapeptide with innate immunity
      properties from acidic proline-rich proteins by proteolytic activity in commensal
      streptococcus and actinomyces species.
AB  - This study suggests degradation of salivary acidic proline-rich proteins (PRPs)
      into potential innate-immunity-like peptides by oral Streptococcus and
      Actinomyces species. PRP degradation paralleled cleavage of Pro-containing
      substrates. PRP degradation by S. gordonii strain SK12 instantly released a
      Pyr(1)-Pro(104)Pro(105) and a Gly(111)-Pro(149)Gln(150) peptide together with a
      presumed Arg(106)Gly(107)Arg(108)Pro(109)Gln(110) pentapeptide. The synthetic
      Arg(106)Gly(107)Arg(108)Pro(109)Gln(110) peptide desorbed bound bacteria and
      counteracted sucrose-induced decrease of dental plaque pH in vitro.

PMID- 10948178
TI  - Cl(-) secretion in colonic epithelial cells induced by the vibrio
      parahaemolyticus hemolytic toxin related to thermostable direct hemolysin.
AB  - A hemolytic toxin related to thermostable direct hemolysin (TDH), TDH-related
      hemolysin (TRH), produced by Kanagawa-phenomenon-negative Vibrio parahaemolyticus
      is suspected of playing an important, but yet-to-be-elucidated role in diarrhea
      caused by this organism. In cultured human colonic epithelial cells, TRH
      increases Cl(-) secretion, followed by elevation of intracellular calcium.

PMID- 10948177
TI  - Maternal Trypanosoma cruzi infection upregulates capacity of uninfected neonate
      cells To produce pro- and anti-inflammatory cytokines.
AB  - The possibility of maternal in utero modulation of the innate and/or adaptive
      immune responses of uninfected newborns from Trypanosoma cruzi-infected mothers
      was investigated by studying the capacity of their whole blood cells to produce
      cytokines in response to T. cruzi lysate or lipopolysaccharide-plus
      phytohemagglutinin (LPS-PHA) stimulation. Cells of such newborns occasionally
      released gamma interferon (IFN-gamma) and no interleukin-2 (IL-2) and IL-4 upon
      specific stimulation, while their mothers responded by the production of IFN
      gamma, IL-2, and IL-4. Infection in mothers was also associated with a
      hyperactivation of maternal cells and also, strikingly, of cells of their
      uninfected neonates, since their release of proinflammatory (IL-1beta, IL-6, and
      tumor necrosis factor alpha [TNF-alpha]) as well as of anti-inflammatory (IL-10
      and soluble TNF receptor) cytokines or factors was upregulated in the presence of
      LPS-PHA and/or parasite lysate. These results show that T. cruzi infection in
      mothers induces profound perturbations in the cytokine response of their
      uninfected neonates. Such maternal influence on neonatal innate immunity might
      contribute to limit the occurrence and severity of congenital infection.

PMID- 10948179
TI  - Amino acid transport into cultured McCoy cells infected with Chlamydia
      trachomatis.
AB  - Amino acid transport into McCoy cells infected with strains representative of the
      two major biovars of Chlamydia trachomatis has been studied to determine if
      uptake is increased during infection. Preliminary work suggested that the
      transport systems L, A/ASC (for neutral amino acid transport), N (for transport
      of Asn, Gln, and His) and y+ (for cationic amino acids) were present in McCoy
      cells. With lymphogranuloma venereum biovar strain 434, little difference in the
      influx of representative amino acids Trp, His, and Lys or the analogue 2
      aminoisobutyric acid (AIB) was observed during infection. With trachoma biovar
      strain DK20, a small increase in the initial entry rate and equilibrium
      concentration of each amino acid was found. McCoy cells appear to have great
      capacity for concentrating amino acids, which might obviate the need for
      transport induction by chlamydiae under conditions favoring the growth of
      infectious organisms.

PMID- 10948180
TI  - Contribution of clumping factor B to pathogenesis of experimental endocarditis
      due to Staphylococcus aureus.
AB  - Staphylococcus aureus Newman with an insertion mutation in clfB, the gene
      encoding clumping factor B, only marginally decreased infection rate (P>0.05) in
      rats with experimental endocarditis. In contrast, clfB complementation on a
      multicopy plasmid significantly increased infectivity (P<0.05) over the deleted
      mutants. Although clfB could affect endovascular infection, its importance in
      experimental endocarditis was limited.

PMID- 10948181
TI  - Direct evidence for involvement of NF-kappaB in transcriptional activation of
      tumor necrosis factor by a spirochetal lipoprotein.
AB  - Variable major lipoprotein (Vmp) is a major tumor necrosis factor (TNF)-inducing
      component of Borrelia recurrentis, the agent of louse-borne relapsing fever. B.
      recurrentis Vmp rapidly stimulates nuclear translocation of NF-kappaB and
      proinflammatory cytokine gene expression in the human monocyte-like cell line
      MonoMac 6. By overexpressing disabled mutant IkappaBalpha in MonoMac 6 cells
      cotransfected with a reporter gene, we provide evidence that NF-kappaB is
      essential for the transcriptional activation of TNF in this system.

PMID- 10948182
TI  - Random transposon mutagenesis of Campylobacter jejuni.
AB  - Genetic studies of Campylobacter jejuni have been limited due to the lack of a
      transposon mutagenesis method. Here, we describe a novel technique for random
      transposon mutagenesis using a mariner-based transposon into C. jejuni strain
      480. Insertions were random, as demonstrated by Southern blot analysis and
      insertional junction sequencing. We have demonstrated, for the first time, random
      in vivo transposon mutagenesis of C. jejuni.

PMID- 10948184
TI  - CD4(+) depletion selectively inhibits eosinophil recruitment to the cornea and
      abrogates Onchocerca volvulus keratitis (River blindness).
AB  - Previous studies demonstrated that in the murine model of Onchocerca volvulus
      keratitis, neutrophils and eosinophils are recruited into the cornea in a
      biphasic manner in response to intrastromal injection. To determine if CD4(+) T
      cells regulate migration of neutrophils and eosinophils into the cornea, CD4(+)
      cells were depleted using monoclonal antibody GK1.5 before intrastromal injection
      of parasite antigens. Depletion of CD4(+) cells abrogated corneal opacification
      at later but not early stages of disease. Consistent with this observation, CD4
      depletion significantly impaired recruitment of eosinophils to the cornea but had
      no effect on neutrophils. These data indicate that CD4(+) T cells mediate
      sustained O. volvulus keratitis by regulating eosinophil recruitment to the
      cornea.

PMID- 10948183
TI  - Analysis of genes expressed at the infective larval stage validates utility of
      Litomosoides sigmodontis as a murine model for filarial vaccine development.
AB  - We used an expressed sequence tag approach to analyze genes expressed by the
      infective larvae of the rodent filarial parasite Litomosoides sigmodontis. One
      hundred fifty two new genes were identified, including several proposed as
      vaccine candidates in studies with human filarial parasites. Our findings have
      important implications for the use of L. sigmodontis as a model for filarial
      infection.

PMID- 10948185
TI  - Role of inducible nitric oxide synthase in resistance to Mycobacterium leprae in
      mice.
AB  - The manifestation of leprosy in humans is largely determined by host immunity to
      Mycobacterium leprae and is a model for immunoregulation in a human disease.
      However, animal models available for exploration of the leprosy spectrum are
      inadequate. This study explored M. leprae infection in mice deficient in
      inducible nitric oxide synthase, and this report describes elements resembling
      borderline tuberculoid leprosy in humans.

PMID- 10948186
TI  - Presence of phosphorylcholine on a filarial nematode protein influences
      immunoglobulin G subclass response to the molecule by an interleukin-10-dependent
      mechanism.
AB  - The filarial nematode product ES-62 contains phosphorylcholine (PC) covalently
      attached to N-linked glycans. ES-62 induced high levels of immunoglobulin G1
      (IgG1) antibodies, but no IgG2a, to non-PC epitopes of the molecule following
      subcutaneous injection into BALB/c mice. Conversely, mice given ES-62 lacking PC
      demonstrated significant production of both IgG subclasses. Thus, PC appears to
      block production of IgG2a antibodies to other epitopes on the parasite molecule.
      A role for interleukin-10 (IL-10) in this effect was shown by the ability of IL
      10(-/-) mice to make an IgG2a antibody response to non-PC epitopes of ES-62.

PMID- 10948187
TI  - Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital
      heart disease.
AB  - A homeodomain-containing transcription factor Csx/Nkx-2.5 is an important
      regulator of cardiogenesis in mammals. Three different mutants, Gln170ter
      (designated A) and Thr178Met (designated B) in the helix 2 of the homeodomain and
      Gln198ter mutation (designated C) just after homeodomain, have been reported to
      cause atrial septal defect with atrial ventricular block. We here examined the
      functions of these three mutants of Csx/Nkx-2.5. The atrial natriuretic peptide
      (ANP) promoter was activated by wild type Csx/Nkx-2.5 (WT, approximately 8-fold),
      B ( approximately 2-fold), and C ( approximately 6-fold) but not by A. When A, B,
      or C was cotransfected into COS-7 cells with the same amount of WT, WT-induced
      activation of the ANP promoter was attenuated by A and B (A > B), whereas C
      further enhanced the activation. Immunocytochemical analysis using anti-Myc tag
      antibody indicated that transfected Myc-tagged WT, B, and C were localized in the
      nucleus of both COS-7 cells and cardiomyocytes of neonatal rats, whereas A was
      distributed diffusely in the cytoplasm and nucleus in COS-7 cells.
      Electrophoretic mobility shift assay showed that Csx/Nkx-2.5-binding sequences
      were bound strongly by WT and C, weakly by B, but not by A. Immunoprecipitation
      and GST pull-down assay revealed that WT and all mutants interacted with GATA-4.
      The synergistic activation of the ANP promoter by WT and GATA-4 was further
      enhanced by C but was inhibited by A and B. In the cultured cardiomyocytes,
      overexpression of C but not WT, A, or B, induced apoptosis. These results suggest
      that although the three mutants induce the same cardiac phenotype,
      transactivation ability and DNA binding ability are different among the three
      mutants and that apoptosis may be a cause for C-induced cardiac defect.

PMID- 10948188
TI  - Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy
      chain genes in association with Syk activation.
AB  - Signals transmitted by class II major histocompatibility complex are important
      regarding cell function related to antigen presentation. We examined effects of
      DR-mediated signaling on Ig production from B cells. Cross-linking HLA-DR
      molecules on B cells by solid-phase anti-HLA-DR monoclonal antibodies, led to an
      increased production of IgM, without proliferation or apoptosis. This event was
      accompanied by an enhanced expression of both membrane- and secretory-type IgM
      heavy chain mRNA. When peptide-pulsed B cells were co-incubated with an HLA-DR
      restricted T cell clone treated by the protein synthesis inhibitor emetine,
      peptide-induced de novo expression of lymphokines and cell-surface molecules on T
      cells can be neglected. CD40-CD154 interaction was not involved in IgM
      enhancement, in such a system. The protein-tyrosine kinase inhibitors and the Syk
      inhibitor piceatannol, but not the Src inhibitor PP2 had a marked inhibitory
      effect on IgM secretion. Furthermore, ligation of HLA-DR on B cells using the
      F(ab')2 fragment of anti-DR monoclonal antibody, enhanced Syk activity. Our data
      suggest that HLA-DR on B cells not only present antigenic peptides to T cells,
      but also up-regulate IgM production, in association with Syk activation and
      without the involvement of Src kinases, hence the possible physiological
      relevance of Src-independent Syk activation.

PMID- 10948189
TI  - Multisite fluorescence in proteins with multiple tryptophan residues.
      Apomyoglobin natural variants and site-directed mutants.
AB  - Time-resolved fluorescence experiments were carried out on a variety of
      apomyoglobins with one or two tryptophan (Trp) residues located at invariant
      positions 7 and 14 in the primary sequence. In all cases, the Trp fluorescence
      kinetics were resolved adequately into two discrete lifetime domains, and decay
      associated spectra (DAS) were obtained for each decay component. The DAS resolved
      for unfolded proteins were indistinguishable by position of the emission maxima
      and the spectral shapes. The folded proteins revealed noticeable differences in
      the DAS, which relate to the diverse local environments around the Trp residues
      in the individual proteins. Furthermore, the DAS of wild-type protein possessing
      two Trp residues were simulated well by that of one Trp mutants either in the
      native, molten globule, or unfolded states. Overall, employing Trp fluorescence
      and site-directed mutagenesis allowed us to highlight the conformational changes
      induced by the single amino acid replacement and generate novel structural
      information on equilibrium folding intermediates. Specifically, it was found that
      conformational fluctuations in the local cluster around the evolutionarily
      conserved Trp(14) are very similar in the native and molten globule states of
      apomyoglobins. This result indicates that residues in the E and B helices
      contributing to this cluster are most likely involved in the stabilization of the
      overall architecture of the structured molten globule intermediate.

PMID- 10948190
TI  - The trio guanine nucleotide exchange factor is a RhoA target. Binding of RhoA to
      the trio immunoglobulin-like domain.
AB  - Trio is a complex protein containing two guanine nucleotide exchange factor
      domains each with associated pleckstrin homology domains, a serine/threonine
      kinase domain, two SH3 domains, an immunoglobulin-like domain, and spectrin-like
      repeats. Trio was originally identified as a LAR tyrosine phosphatase-binding
      protein and is involved in actin remodeling, cell migration, and cell growth.
      Herein we provide evidence that Trio not only activates RhoA but is also a RhoA
      target. The RhoA-binding site was mapped to the Trio immunoglobulin-like domain.
      RhoA isoprenylation is necessary for the RhoA-Trio interaction, because mutation
      of the RhoA carboxyl-terminal cysteine residue blocked binding. The existence of
      an intramolecular functional link between RhoA activation and RhoA binding is
      suggested by the finding that Trio exchange activity enhanced RhoA binding to
      Trio. Furthermore, immunofluorescence studies of HeLa cells showed that although
      ectopically expressed Trio was evenly distributed within the cell, co-expression
      of Trio with RhoA resulted in relocalization of Trio into punctate structures.
      Relocalization was not observed with Trio constructs lacking the immunoglobulin
      like domain, indicating that RhoA acts to regulate Trio localization via binding
      to the immunoglobulin-like domain. We propose that Trio-mediated RhoA activation
      and subsequent RhoA-mediated relocalization of Trio functions to modulate and
      coordinate Trio signaling.

PMID- 10948191
TI  - An asn to lys polymorphism in the third intracellular loop of the human alpha 2A
      adrenergic receptor imparts enhanced agonist-promoted Gi coupling.
AB  - alpha(2A)-Adrenergic receptors (alpha(2A)AR) are presynaptic autoinhibitory
      receptors of noradrenergic neurons in the central and peripheral sympathetic
      nervous systems, which act to dynamically regulate neurotransmitter release.
      Signaling through the G(i)/G(o) family of G-proteins, the receptor subserves
      numerous homeostatic and central nervous system functions. A single nucleotide
      polymorphism of this receptor, which results in an Asn to Lys substitution at
      amino acid 251 of the third intracellular loop, was identified in the human
      population. The frequency of Lys-251 was 10-fold greater in African-Americans
      than in Caucasians, but was not associated with essential hypertension. To
      determine the consequences of this substitution, wild-type and Lys-251 receptors
      were expressed in CHO and COS-7 cells. Expression, ligand binding, and basal
      receptor function were unaffected by the substitution. However, agonist-promoted
      [(35)S]GTPgammaS binding was approximately 40% greater with the Lys-251 receptor.
      This enhanced agonist function was observed with catecholamines, azepines, and
      imidazolines albeit to different degrees. In studies of agonist-promoted
      functional coupling to G(i), the polymorphic receptor displayed enhanced
      inhibition of adenylyl cyclase (60 +/- 4. 4 versus 46 +/- 4.1% inhibition) and
      markedly enhanced stimulation of MAP kinase (57 +/- 9 versus 15- +/- 2-fold
      increase over basal) compared with wild-type alpha(2A)AR. The potency of
      epinephrine in stimulating inositol phosphate accumulation was increased
      approximately 4 fold with the Lys-251 receptor. Unlike previously described
      variants of G-protein-coupled receptors, where the minor species causes either a
      loss of function or increased non-agonist function, Lys-251 alpha(2A)AR
      represents a new class of polymorphism whose phenotype is a gain of agonist
      promoted function.

PMID- 10948192
TI  - Interleukin-11 signals through the formation of a hexameric receptor complex.
AB  - Interleukin-11 (IL-11) is a member of the gp130 family of cytokines. These
      cytokines drive the assembly of multisubunit receptor complexes, all of which
      contain at least one molecule of the transmembrane signaling receptor gp130. IL
      11 has been shown to induce gp130-dependent signaling through the formation of a
      high affinity complex with the IL-11 receptor (IL-11R) and gp130. Site-directed
      mutagenesis studies have identified three distinct receptor binding sites of IL
      11, which enable it to form this high affinity receptor complex. Here we present
      data from immunoprecipitation experiments, using differentially tagged forms of
      ligand and soluble receptor components, which show that multiple copies of IL-11,
      IL-11R, and gp130 are present in the receptor complex. Furthermore, it is
      demonstrated that sites II and III of IL-11 are independent gp130 binding
      epitopes and that both are essential for gp130 dimerization. We also show that a
      stable high affinity complex of IL-11, IL-11R, and gp130 can be resolved by
      nondenaturing polyacrylamide gel electrophoresis, and its composition verified by
      second dimension denaturing polyacrylamide gel electrophoresis. Results indicate
      that the three receptor binding sites of IL-11 and the Ig-like domain of gp130
      are all essential for this stable receptor complex to be formed. We therefore
      propose that IL-11 forms a hexameric receptor complex composed of two molecules
      each of IL-11, IL-11R, and gp130.

PMID- 10948193
TI  - Expression and characterization of soluble and membrane-bound human nucleoside
      triphosphate diphosphohydrolase 6 (CD39L2).
AB  - Ecto-nucleoside-triphosphate diphosphohydrolase-6 (eNTPDase6(1), also known as
      CD39L2) cDNA was expressed in mammalian COS-1 cells and characterized using
      nucleotidase assays as well as size exclusion, anion exchange, and cation
      exchange chromatography. The deduced amino acid sequence of eNTPDase6 is more
      homologous with the soluble E-type ATPase, eNTPDase5, than other E-type ATPases,
      suggesting it may also be soluble. To test this possibility, both the cell
      membranes and the growth media from eNTPDase6-transfected COS-1 cells were
      assayed for nucleotidase activities. Activity was found in both the membranes and
      the media. Soluble eNTPDase6 preferentially exhibits nucleoside diphosphatase
      activity, which is dependent on the presence of divalent cations. Western blot
      analysis of eNTPDase6 treated with PNGase-F indicated both soluble and membrane
      bound forms are glycosylated. However, unlike some membrane-bound ecto
      nucleotidases, the eNTPDase6 activity was not specifically inhibited by
      deglycosylation with peptide N-glycosidase F. Soluble eNTPDase6 hydrolyzed
      nucleoside triphosphates poorly and nucleoside monophosphates not at all.
      Analysis of the relative rates of hydrolysis of nucleoside diphosphates (GDP =
      IDP > UDP > CDP >> ADP) suggests that soluble eNTPDase6 is a diphosphatase most
      likely not involved in regulation of ADP levels important for circulatory
      hemostasis.

PMID- 10948194
TI  - DIK, a novel protein kinase that interacts with protein kinase Cdelta. Cloning,
      characterization, and gene analysis.
AB  - A novel serine/threonine kinase, termed DIK, was cloned using the yeast two
      hybrid system to screen a cDNA library from the human keratinocyte cell line
      HaCaT with the catalytic domain of rat protein kinase Cdelta (PKCdelta(cat)) cDNA
      as bait. The predicted 784-amino acid polypeptide with a calculated molecular
      mass of 86 kDa contains a catalytic kinase domain and a putative regulatory
      domain with ankyrin-like repeats and a nuclear localization signal. Expression of
      DIK at the mRNA and protein level could be demonstrated in several cell lines.
      The dik gene is located on chromosome 21q22.3 and possesses 8 exons and 7
      introns. DIK was synthesized in an in vitro transcription/translation system and
      expressed as recombinant protein in bacteria, HEK, COS-7, and baculovirus
      infected insect cells. In the in vitro system and in cells, but not in bacteria,
      various post-translationally modified forms of DIK were produced. DIK was shown
      to exhibit protein kinase activity toward autophosphorylation and substrate
      phosphorylation. The interaction of PKCdelta(cat) and PKCdelta with DIK was
      confirmed by coimmunoprecipitation of the proteins from HEK cells transiently
      transfected with PKCdelta(cat) or PKCdelta and DIK expression constructs.

PMID- 10948195
TI  - Competitive substrate and inhibitor interactions at the physiologically relevant
      active site of nitrogenase.
AB  - Nitrogenase catalyzes the MgATP-dependent reduction of dinitrogen gas to ammonia.
      In addition to the physiological substrate, nitrogenase catalyzes reduction of a
      variety of other multiply bonded substrates, such as acetylene, nitrous oxide,
      and azide. Although carbon monoxide (CO) is not reduced by nitrogenase, it is a
      potent inhibitor of all nitrogenase catalyzed substrate reductions except proton
      reduction. Here, we present kinetic parameters for an altered Azotobacter
      vinelandii MoFe protein for which the alphaGly(69) residue was substituted by
      serine (Christiansen, J., Cash, V. L., Seefeldt, L. C., and Dean, D. R. (2000) J.
      Biol. Chem. 275, 11459-11464). For the wild type enzyme, CO and acetylene are
      both noncompetitive inhibitors of dinitrogen reduction. However, for the
      alphaSer(69) MoFe protein both CO and acetylene have become competitive
      inhibitors of dinitrogen reduction. CO is also converted from a noncompetitive
      inhibitor to a competitive inhibitor of acetylene, nitrous oxide, and azide
      reduction. These results are interpreted in terms of a two-site model. Site 1 is
      a high affinity acetylene-binding site to which CO also binds, but dinitrogen,
      azide, and nitrous oxide do not bind. This site is the one primarily accessed
      during typical acetylene reduction assays. Site 2 is a low affinity acetylene
      binding site to which CO, dinitrogen, azide, and nitrous oxide also bind. Site 1
      and site 2 are proposed to be located in close proximity within a specific 4Fe-4S
      face of FeMo cofactor.

PMID- 10948196
TI  - Chicken coagulation factor XIIIA is produced by the theca externa and stabilizes
      the ovarian follicular wall.
AB  - Development of the follicle in egg-laying species such as the chicken is
      regulated by systemic factors as well as by the highly orchestrated interplay of
      differentially expressed genes within this organ. Differential mRNA display
      analysis of defined phases of follicle development resulted in the
      characterization of coagulation factor XIIIA. It is expressed and produced by
      cells of the theca externa in a highly regulated manner during distinct growth
      phases of the follicle. Transcripts for factor XIIIA are already detectable at
      the beginning of follicle development and peak at the end of phase 2. Protein
      levels, however, still increase during phase 3, peak shortly after ovulation, and
      persist until the postovulatory tissue is completely resorbed. Factor XIIIA is
      secreted as a monomer into the extracellular matrix of the theca externa and is
      not associated with factor XIIIB as is the case in plasma. Our data suggest that,
      due to its transglutaminase activity, factor XIIIA stabilizes the follicular wall
      by cross-linking matrix components. Thus, coagulation factor XIIIA might play a
      key role in coping with the massive mechanical stress exerted by the large amount
      of yolk accumulating during the rapid growth phase of the oocyte.

PMID- 10948197
TI  - Cell surface-bound collagenase-1 and focal substrate degradation stimulate the
      rear release of motile vascular smooth muscle cells.
AB  - To migrate in the vessel wall, smooth muscle cells (SMCs) must contend with
      abundant type I collagen. We investigated the mechanisms used by human SMCs to
      efficiently migrate on type I collagen, following stimulation with fibroblast
      growth factor-2 (FGF-2). FGF-2-stimulated migration was inhibited by a hydroxamic
      acid inhibitor of matrix metalloproteinases and by a neutralizing anti
      collagenase-1 antibody. Moreover, migration speed of SMCs plated on mutant
      collagenase-resistant type I collagen was not increased by FGF-2. Time-lapse
      video analysis of unstimulated SMCs migrating on collagen revealed discrete
      phases of leading edge membrane extension and rear retraction, the latter often
      after rupture of an elongated tail. FGF-2 stimulation yielded a more synchronous,
      gliding motion with a collagenase-1-mediated decrease in tail ripping. Surface
      labeling of SMCs with biotin followed by immunoprecipitation revealed that a
      proportion of active collagenase-1, expressed in response to FGF-2, was bound to
      the plasma membrane. Pericellular collagen substrate cleavage was verified by
      immunostaining for neoepitopes generated by collagenase-1 action and was
      localized to discrete zones beneath the cell tail and the leading edge. These
      results identify a novel mechanism by which SMC migration on collagen is
      enhanced, whereby rear release from the substrate is orchestrated by the
      localized actions of membrane-bound collagenase-1.

PMID- 10948198
TI  - Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3
      adrenergic receptor-deficient mice promotes diet-induced obesity.
AB  - Catecholamines play an important role in controlling white adipose tissue
      function and development. beta- and alpha 2-adrenergic receptors (ARs) couple
      positively and negatively, respectively, to adenylyl cyclase and are co-expressed
      in human adipocytes. Previous studies have demonstrated increased adipocyte alpha
      2/beta-AR balance in obesity, and it has been proposed that increased alpha 2-ARs
      in adipose tissue with or without decreased beta-ARs may contribute
      mechanistically to the development of increased fat mass. To critically test this
      hypothesis, adipocyte alpha 2/beta-AR balance was genetically manipulated in
      mice. Human alpha 2A-ARs were transgenically expressed in the adipose tissue of
      mice that were either homozygous (-/-) or heterozygous (+/-) for a disrupted beta
      3-AR allele. Mice expressing alpha 2-ARs in fat, in the absence of beta 3-ARs
      (beta 3-AR -/- background), developed high fat diet-induced obesity. Strikingly,
      this effect was due entirely to adipocyte hyperplasia and required the presence
      of alpha2-ARs, the absence of beta 3-ARs, and a high fat diet. Of note, obese
      alpha 2-transgenic beta 3 -/- mice failed to develop insulin resistance, which
      may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and
      not adipocyte hypertrophy. In summary, we have demonstrated that increased alpha
      2/beta-AR balance in adipocytes promotes obesity by stimulating adipocyte
      hyperplasia. This study also demonstrates one way in which two genes (alpha 2 and
      beta 3-AR) and diet interact to influence fat mass.

PMID- 10948199
TI  - Human RNase III is a 160-kDa protein involved in preribosomal RNA processing.
AB  - A human RNase III gene encodes a protein of 160 kDa with multiple domains, a
      proline-rich, a serine- and arginine-rich, and an RNase III domain. The expressed
      purified RNase III domain cleaves double-strand RNA and does not cleave single
      strand RNA. The gene is ubiquitously expressed in human tissues and cell lines,
      and the protein is localized in the nucleus of the cell. The levels of
      transcription and translation of the protein do not change during different
      phases of the cell cycle. However, a significant fraction of the protein in the
      nucleus is translocated to the nucleolus during the S phase of the cell cycle.
      That this human RNase III is involved in processing of pre-rRNA, but might cleave
      at sites different from those described for yeast RNase III, is shown by
      antisense inhibition of RNase III expression. Inhibition of human RNase III
      expression causes cell death, suggesting an essential role for human RNase III in
      the cell. The antisense inhibition technique used in this study provides an
      effective method for functional analysis of newly identified human genes.

PMID- 10948200
TI  - Mutations in retinoid X receptor that impair heterodimerization with specific
      nuclear hormone receptor.
AB  - Retinoid X receptor (RXR) serves as a promiscuous heterodimerization partner for
      many nuclear receptors through the identity box, a 40-amino acid subregion within
      the ligand binding domain. In this study, we randomly mutated two specific
      residues within the human RXRalpha identity box region previously identified as
      important determinants in heterodimerization (i.e. Ala(416) and Arg(421)).
      Interestingly, most of these mutants still retained wild type interactions with
      thyroid hormone receptor (TR), retinoic acid receptor, peroxisome proliferator
      activated receptor alpha, small heterodimer partner, and constitutive androstane
      receptor. However, RXR-A416D and R421L were specifically impaired for
      interactions with TR, whereas RXR-A416K lost both TR and retinoic acid receptor
      interactions. Accordingly, RXR-A416D did not support T3 transactivation in
      mammalian cells, whereas RXR-A416K was not supportive of transactivation by
      retinoids or T3. These results provide a basis upon which to further design
      mutant RXRs highly selective in heterodimerization, potentially useful tools to
      probe nuclear receptor function in vivo.

PMID- 10948201
TI  - The location of the mobile electron carrier ferredoxin in vascular plant
      photosystem I.
AB  - In this study, we present the location of the ferredoxin-binding site in
      photosystem I from spinach. Image analysis of negatively stained two-dimensional
      crystals indicates that the addition of ferredoxin and chemical cross-linkers do
      not significantly alter the unit cell parameters (for untreated photosystem I, a
      = 26.4 nm, b = 27.6 nm, and gamma = 90 degrees, space group p22(1)2(1) and for
      ferredoxin cross-linked photosystem I, a = 26.2 nm, b = 27.2 nm, and gamma = 90
      degrees, space group p22(1)2(1)). Fourier difference analysis reveals that
      ferredoxin is bound on top of the stromal ridge principally interacting with the
      extrinsic subunits PsaC and PsaE. This location would be accessible to the
      stroma, thereby promoting efficient electron transfer away from photosystem I.
      This observation is significantly different from that of the ferredoxin binding
      site proposed for cyanobacteria. A model for the binding of ferredoxin in
      vascular plants is proposed and is discussed relative to observations in
      cyanobacteria.

PMID- 10948202
TI  - Two distinct triggers for cycling of the lagging strand polymerase at the
      replication fork.
AB  - There are two modes of DNA synthesis at a replication fork. The leading strand is
      synthesized in a continuous fashion in lengths that in Escherichia coli can be in
      excess of 2 megabases. On the other hand, the lagging strand is synthesized in
      relatively short stretches of 2 kilobases. Nevertheless, identical assemblies of
      the DNA polymerase III core tethered to the beta sliding clamp account for both
      modes of DNA synthesis. Yet the same lagging strand polymerase accounts for the
      synthesis of all Okazaki fragments at a replication fork, cycling repeatedly
      every 1 or 2 s from the 3'-end of the just-completed fragment to the 3'-end of
      the new primer. Several models have been invoked to account for the rapid cycling
      of a polymerase complex that can remain bound to the template for upward of 40
      min. By using isolated replication protein-DNA template complexes, we have tested
      these models and show here that cycling of the lagging strand polymerase can be
      triggered by either the action of primase binding to the replisome and
      synthesizing a primer or by collision of the lagging strand polymerase with the
      5'-end of the previous Okazaki fragment.

PMID- 10948203
TI  - Head-to-tail polymerization of coagulin, a clottable protein of the horseshoe
      crab.
AB  - A clottable protein coagulogen of the horseshoe crab Tachypleus tridentatus is
      proteolytically converted into an insoluble coagulin gel through non-covalent
      self-polymerization. Here we identified binding sites for the polymerization. A
      tryptic fragment, derived from the coagulin polymer chemically cross-linked by a
      bifunctional cross-linker, was isolated. Amino acid sequence analysis indicated
      that the fragment consists of two peptides cross-linked between Lys(85) and
      Lys(156). The two lysine residues are oppositely located at the head and tail
      regions of the elongated molecule separated by a much greater distance than the
      length of the cross-linker, which suggests that the cross-linking occurs
      intermolecularly. Based on the x-ray structural analysis, exposure of a
      hydrophobic cove on the head in response to the release of peptide C has been
      postulated (Bergner, A., Oganessyan, V., Muta, T., Iwanaga, S., Typke, D., Huber,
      R., and Bode, W. (1996) EMBO J. 15, 6789-6797). An octapeptide containing
      Tyr(136), which occupies the tail end of coagulin, was found to inhibit the
      polymerization. Replacement of Tyr(136) of the peptide with Ala resulted in loss
      of the inhibitory activity. These results indicated that the polymerization of
      coagulin proceeds through the interaction between the newly exposed hydrophobic
      cove on the head and the wedge-shaped hydrophobic tail.

PMID- 10948204
TI  - Serine 121 is an essential amino acid for biotin sulfoxide reductase
      functionality.
AB  - Rhodobacter sphaeroides f. sp. denitrificans biotin sulfoxide reductase (BSOR)
      catalyzes the reduction of d-biotin d-sulfoxide (BSO) to biotin, an important
      step in oxidized vitamin salvaging. In addition to BSO, the enzyme also catalyzes
      the reduction of a variety of other substrates, including methionine sulfoxide,
      with decreased efficiencies, suggesting a potential role as a general cell
      protector against oxidative damage. Recombinant BSOR, expressed as a glutathione
      S-transferase fusion protein, contains the molybdopterin guanine dinucleotide
      cofactor (MGD) as its sole prosthetic group, which is required for the reduction
      of BSO by either NADPH or reduced methyl viologen. Comparison of the amino acid
      sequences of BSOR and the closely related MGD-containing enzyme, dimethyl
      sulfoxide reductase, has indicated a number of conserved residues, including an
      active site serine residue, serine 121, which has been potentially identified as
      the fifth coordinating ligand of Mo in BSOR. Site-directed mutagenesis has been
      used to replace serine 121 with cysteine, threonine, or alanine residues in the
      BSOR sequence to asses the role of this residue in catalysis and/or Mo
      coordination. All three BSOR mutant proteins were expressed, purified to
      homogeneity, and demonstrated to contain both MGD by fluorescence spectroscopy
      and Mo by inductively coupled plasma mass spectrometry, similar to wild-type
      enzyme. However, all three mutant proteins were devoid of BSOR activity using
      either NADPH or reduced methyl viologen as the electron donor. These results
      strongly suggest that serine 121 in BSOR is essential for catalysis but is not
      essential for either Mo coordination or MGD binding.

PMID- 10948205
TI  - Characterization of CD1e, a third type of CD1 molecule expressed in dendritic
      cells.
AB  - Dendritic cells express several alternatively spliced CD1e mRNAs. These molecules
      encode proteins characterized by the presence of either one, two, or three alpha
      domains and either a 51- or 63-amino acid cytoplasmic domain. Moreover, mRNAs
      encoding isoforms lacking the transmembrane domain are observed. Several of these
      CD1e isoforms were expressed in transfected cells, and two of them, with three
      alpha domains, displayed a particular processing pathway. These latter isoforms
      slowly leave the endoplasmic reticulum due to the presence of atypical dilysine
      motifs in the cytoplasmic tail. These molecules are associated with the beta(2)
      microglobulin and accumulate in late Golgi and late endosomal compartments. In
      the latter compartments, they are cleaved into soluble forms that appear to be
      stable. In dendritic cells, these isoforms are mainly located in the Golgi
      apparatus, and upon maturation they are redistributed to late endosomal
      compartments. This work demonstrates the existence of CD1e molecules. As compared
      with other CD1 molecules, CD1e displays fundamentally different properties and
      therefore may represent a third type of CD1 molecules.

PMID- 10948206
TI  - The vitamin D response element-binding protein. A novel dominant-negative
      regulator of vitamin D-directed transactivation.
AB  - Vitamin D resistance in certain primate genera is associated with the
      constitutive overexpression of a non-vitamin D receptor (VDR)-related, vitamin D
      response element-binding protein (VDRE-BP) and squelching of vitamin d-directed
      transactivation. We used DNA affinity chromatography to purify proteins
      associated with non-VDR-VDRE binding activity from vitamin d-resistant New World
      primate cells. In electrophoretic mobility shift assays, these proteins bound
      specifically to either single-strand or double-strand oligonucleotides harboring
      the VDRE. Amino acid sequencing of tryptic peptides from a 34-kDa (VDRE-BP1) and
      38-kDa species (VDRE-BP-2) possessed sequence homology with human heterogeneous
      nuclear ribonucleoprotein (hnRNP) A1 and hnRNPA2, respectively. cDNAs bearing the
      open reading frame for both VDRE-BPs were cloned and used to transfect wild-type,
      hormone-responsive primate cells. Transient and stable overexpression of the VDRE
      BP2 cDNA, but not the VDRE-BP1 cDNA, in wild-type cells with a VDRE-luciferase
      reporter resulted in significant reduction in reporter activity. These data
      suggest that the hnRNPA2-related VDRE-BP2 is a dominant-negative regulator of
      vitamin D action.

PMID- 10948207
TI  - Perilipin A increases triacylglycerol storage by decreasing the rate of
      triacylglycerol hydrolysis.
AB  - The perilipins are the most abundant proteins at the surfaces of lipid droplets
      in adipocytes and are also found in steroidogenic cells. To investigate perilipin
      function, perilipin A, the predominant isoform, was ectopically expressed in
      fibroblastic 3T3-L1 pre-adipocytes that normally lack the perilipins. In control
      cells, fluorescent staining of neutral lipids with Bodipy 493/503 showed a few
      minute and widely dispersed lipid droplets, while in cells stably expressing
      perilipin A, the lipid droplets were more numerous and tightly clustered in one
      or two regions of the cytoplasm. Immunofluorescence microscopy revealed that the
      ectopic perilipin A localized to the surfaces of the tiny clustered lipid
      droplets; subcellular fractionation of the cells using sucrose gradients
      confirmed that the perilipin A localized exclusively to lipid droplets. Cells
      expressing perilipin A stored 6-30-fold more triacylglycerol than control cells
      due to reduced lipolysis of triacylglycerol stores. The lipolysis of stored
      triacylglycerol was 5 times slower in lipid-loaded cells expressing perilipin A
      than in lipid-loaded control cells, when triacylglycerol synthesis was blocked
      with 6 microm triacsin C. This stabilization of triacylglycerol was not due to
      the suppression of triacylglycerol lipase activity by the expression of perilipin
      A. We conclude that perilipin A increases the triacylglycerol content of cells by
      forming a barrier that reduces the access of soluble lipases to stored lipids,
      thus inhibiting triacylglycerol hydrolysis. These studies suggest that perilipin
      A plays a major role in the regulation of triacylglycerol storage and lipolysis
      in adipocytes.

PMID- 10948208
TI  - The generation and modification of cell polarity.
AB  - The generation of polarity in the cells of eukaryotes in most cases requires an
      external asymmetrical input. This signal may originate from a random event such
      as the point of penetration of an egg by a sperm or from asymmetries present in
      the maternal environment as, for example, in megasporogenesis in flowering
      plants, or from an asymmetry in the physical environment usually involving either
      light or gravity. The latter affords the best opportunities for experimental
      manipulation and single cell systems in algae, mosses and ferns allow both cell
      biological and genetical investigation of the mechanisms establishing polarity.
      These simple systems have already shown that the generation of polarity involves
      two distinguishable processes, axis alignment and axis orientation, but a
      detailed understanding of the mechanisms by which the environmental inputs are
      transduced to set up a polar axis is still lacking. Non-motile organisms must
      also be able to modify cell polarity in response to changed environmental inputs,
      and here too, lower plant systems afford the best prospect for understanding the
      mechanisms responsible.

PMID- 10948209
TI  - Evidence of two enzymes performing the de-N-glycosylation of proteins in barley:
      expression during germination, localization within the grain and set-up during
      grain formation.
AB  - The occurrence of two enzymes performing de-N-glycosylation of glycoproteins,
      namely, endo-N-acetyl-beta-D-glucosaminidase (ENGase, EC 3.2.1.96) and peptide
      N(4)-(N-acetyl-beta-D-glucosaminyl) asparagine amidase (PNGase, EC 3.5.1.52) was
      investigated in barley, cv. Plaisant (a winter six rowed variety). The dry grain
      showed both activities according to the HPLC detection of the hydrolysis of
      fluorescent resorufin-labelled substrates. However, PNGase activity was 16-fold
      higher than ENGase activity. During germination, both activities increased,
      PNGase by only 1.5-fold compared to nearly 4.8-fold for ENGase over the 4 d
      following imbibition. The localization of these activities within the grain
      showed that the major contribution of PNGase was due to the endosperm, typically
      representing over 90% of the whole grain activity. In contrast, ENGase activity
      was especially high in the embryo and, later, in the developing plantlet (10-fold
      higher than in the endosperm), particularly in the rootlets and scutellum. In
      developing spikes, PNGase activity was 5.6-fold higher than in the leaves, but
      similar ENGase activity was measured in both organs. During grain formation,
      PNGase activity followed dry matter increase together with endosperm development.
      In contrast, ENGase activity dropped by 66% at the beginning of grain filling
      before stabilizing until harvest. The occurrence of de-N-glycosylation-performing
      enzymes throughout the development of barley raises the question of the nature of
      their natural substrates. Moreover, the prevalence of one of these enzymes over
      the other depending on the organ and the developmental stage, could represent the
      first evidence of specific functions for each enzyme.

PMID- 10948210
TI  - Differential expression of two barley XET-related genes during coleoptile growth.
AB  - Plant cell elongation depends on the physical properties of the primary cell
      wall. Because xyloglucan endotransglycosylases (XETs) are enzymes that mediate
      cleavage and rejoining of the beta(1-4)-XG backbone of primary cell wall, they
      are potentially involved in cell elongation. In this paper, the growth of the
      barley coleoptile was related to the expression patterns of two genes from this
      family (hvEXT, hvXEB) in experiments where coleoptile elongation varied according
      to light/dark treatments in order to assess the potential role of these genes in
      cell elongation. In dark-grown and light-grown coleoptiles, growth rate
      variations were associated with altered levels of expression of hvEXT and hvXEB:
      they were higher in dark-grown than in light-grown seedlings, and decreased after
      5 d in darkness, and after 4 d in continuous light. In 4-d-old seedlings,
      coleoptile elongation decreased significantly 4 h after the onset of a continuous
      white- light irradiation, and hvXEB and hvEXT mRNA levels decreased,
      respectively, 2 h and 4 h after the onset of white-light irradiation. Moreover,
      the distribution of hvXEB and hvEXT along the coleoptiles of 4-d-old dark-grown
      seedlings were different. Altogether, these results suggest a complex pattern of
      temporal and positional expression for the different genes of the XET-related
      family.

PMID- 10948211
TI  - Controlled induction of GUS marked clonal sectors in Arabidopsis.
AB  - Stably transformed Arabidopsis lines in which GUS marked cell clones are readily
      produced in response to heat-shock have been established and characterized.
      Control of GUS activation is achieved by heat-shock-induced FLP recombinase
      activity which "switches on" expression of a GUS marker gene previously held
      transcriptionally silent. To obtain efficient GUS sectoring, single insert
      Arabidopsis lines carrying FLP recombinase under the control of a heat-shock
      inducible promoter and an FLP-activatable GUS construct were generated. Analysis
      of GUS sectoring in lines hemizygous and homozygous for both inserts was
      conducted after various regimes of heat-shock were given at various developmental
      stages. It is shown that GUS sectoring events can be efficiently induced in most
      vegetative, aerial and sexual structures in Arabidopsis. Furthermore, the
      frequency of sectoring events, sector size and, to some extent, the tissues in
      which sectors are generated can be readily controlled by choice of the conditions
      and timing of heat-shock used.

PMID- 10948212
TI  - Mitochondria-targeted GFP highlights the heterogeneity of mitochondrial shape,
      size and movement within living plant cells.
AB  - Little is known concerning the heterogeneity of mitochondrial shape, size,
      number, cytoplasmic distribution, and motility in planta. Ultrastructural studies
      using the electron microscope have shown a variety of mitochondrial shapes and
      sizes within fixed cells, however, it is not possible to dismiss the possibility
      that any heterogeneity observed resulted from preparation or fixation artefacts.
      Unambiguous demonstration of the extent and nature of mitochondrial heterogeneity
      in vivo necessitates the use of a truly in vivo mitochondrial detection system.
      Green fluorescent protein is an excellent in vivo marker for gene expression and
      protein localization studies. It is particularly useful for real-time
      spatiotemporal analysis of intracellular protein targeting and dynamics and as
      such is an ideal marker for analysing mitochondria in planta. Stably transformed
      Arabidopsis lines have been generated with GFP targeted to the mitochondria using
      either of two plant mitochondrial signal sequences from the beta-ATPase subunit
      or the mitochondrial chaperonin CPN-60. Mitochondrially targeted GFP, which is
      easily detectable using an epifluorescent or confocal microscope, highlights
      heterogeneity of mitochondrial shape, size, position, and dynamic within living
      plant cells.

PMID- 10948213
TI  - Carotenoid and ultrastructure variations in plastids of Arum italicum Miller
      fruit during maturation and ripening.
AB  - The changes in the pigment pattern and composition occurring in the Arum italicum
      berry during the various steps of maturation (ivory to deep-green stages) and
      ripening (yellow and red-orange stages) were studied and correlated to the
      ultrastructural modifications of plastids. Transmission electron microscopy
      showed that each stage was characterized by a specific plastidial type following
      the unusual sequence amyloplast-->chloroplast-->chromoplast. Plastidial
      transitions were accompanied by profound modifications in the pigmental
      composition, in particular, in the pattern of carotenoids and their precursors.
      The HPLC analysis of the carotenoids showed that, besides the two usual all-trans
      metabolic pathways leading to lutein through alpha-carotene and to auroxanthin
      through beta-carotene, an additional cis-isomeric biosynthetic pathway leading to
      cis-neoxanthin through cis-beta-carotene exists. During the pre-ripening stages,
      the three pathways were present even if with qualitative and quantitative
      variations. When complete ripening was reached, a block occurred at the
      cyclization level causing the accumulation of both all-trans (i.e. gamma-carotene
      and neurosporene) and cis-isomer (i.e. lycopene and zeta-carotene) carotene
      precursors. Because of the occurrence of unusual pigments and the presence of the
      three main plastidial types, the fruit of A. italicum may constitute a most
      instructive model for the study of carotenogenesis.

PMID- 10948214
TI  - Ethylene is involved in the nodulation phenotype of Pisum sativum R50 (sym 16), a
      pleiotropic mutant that nodulates poorly and has pale green leaves.
AB  - R50 is characterized as a pleiotropic pea mutant; it forms few nodules and has
      short lateral roots, short stature and pale leaves. Using grafting techniques,
      R50 paleness was found to be controlled by the shoot of the mutant whereas the
      nodulation phenotype was regulated by its root. The paleness of R50 is due to a
      lower than normal total chlorophyll content in its young leaves. The defect
      appears to be overcome with age because, as the plant matures, the chlorophyll
      levels increase in the older leaves. The reduction in stature is attributed to
      shorter internodes, and the oldest internodes are thicker than those of the
      parent Sparkle. Upon rhizobial inoculation, R50 forms as many infection threads
      as Sparkle. However, most of these are arrested in the inner cortex. The threads
      appear to have lost their directional growth towards the stele, and they coil
      around within enlarged cortical cells. In addition, very few infection threads
      are associated with divisions of the inner cortical cells. These aborted nodule
      primordia are abnormal, flat and mainly composed of cells which have divided
      anticlinally only. Nodulation of R50 was restored by treating the roots with
      ethylene inhibitors. The R50 mutant further supports the postulated role of
      ethylene in regulating rhizobial infection with a probable role in the control of
      the primordium development.

PMID- 10948215
TI  - Seed coat cell turgor in chickpea is independent of changes in plant and pod
      water potential.
AB  - Turgor pressure in cells of the pod wall and the seed coat of chickpea (Cicer
      arietinum L.) were measured directly with a pressure probe on intact plants under
      initially dry soil conditions, and after the plants were irrigated. The turgor
      pressure in cells of the pod wall was initially 0.25 MPa, and began to increase
      within a few minutes of irrigation. By 2-4 h after irrigation, pod wall cell
      turgor had increased to 0.97 MPa. This increase in turgor was matched closely by
      increases in the total water potential of both the pod and the stem, as measured
      by a pressure chamber. However, turgor pressure in cells of the seed coat was
      relatively low (0.10 MPa) and was essentially unchanged up to 24 h after
      irrigation (0.13 MPa). These data demonstrate that water exchange is relatively
      efficient throughout most of the plant body, but not between the pod and the
      seed. Since both the pod and the seed coat are vascularized tissues of maternal
      origin, this indicates that at least for chickpea, isolation of the water
      relations of the embryo from the maternal plant does not depend on the absence of
      vascular or symplastic connections between the embryo and the maternal plant.

PMID- 10948216
TI  - Does ascorbate in the mesophyll cell walls form the first line of defence against
      ozone? Testing the concept using broad bean (Vicia faba L.).
AB  - Broad bean (Vicia faba L.) plants were exposed, in duplicate controlled
      environment chambers, to charcoal/Purafil-filtered air (CFA-grown plants) or to
      75 nmol mol(-1) ozone (O(3)) for 7 h d(-1) (O(3)-grown plants) for 28 d, and then
      exposed to 150 nmol mol(-1) O(3 )for 8 h. The concentration of ascorbate (ASC)
      was determined in leaf extracellular washing fluid (apoplast) and in the residual
      leaf tissue (symplast) after 0, 4 and 8 h acute fumigation, and after a 16 h
      "recovery" period in CFA. Changes in stomatal conductance were measured in vivo
      in order to model pollutant uptake, while the light-saturated rate of CO(2)
      assimilation (A:(sat)) was recorded as an indicator of O(3)-induced intracellular
      damage. Measurements of A:(sat) revealed enhanced tolerance to 150 nmol mol(-1)
      O(3) in plants pre-exposed to the pollutant compared with equivalent plants grown
      in CFA, consistent with the observed reduction in pollutant uptake due to lower
      stomatal conductance. The concentration of ASC in the leaf apoplast (ASC(apo))
      declined upon O(3)-treatment in both CFA- and O(3)-grown plants, consistent with
      the oxidation of ASC(apo) under O(3)-stress. Furthermore, the decline in ASC(apo)
      was reversible in O(3)-grown plants after a 16 h "recovery" period, but not in
      plants grown in CFA. No significant change in the level and/or redox state of ASC
      in the symplast (ASC(symp)) was observed in plants exposed to 150 nmol mol(-1)
      O(3), and there was no difference in the constitutive level of ASC(symp) between
      CFA- and O(3)-grown plants. Model calculations indicated that the reaction of
      O(3) with ASC(apo) in the leaves of Vicia faba is potentially sufficient to
      intercept a substantial proportion (30-40%) of the O(3)entering the plant under
      environmentally-relevant conditions. The potential role of apoplastic ASC in
      mediating the tolerance of leaves to O(3) is discussed.

PMID- 10948217
TI  - Role of light in the response of PSII photochemistry to salt stress in the
      cyanobacterium Spirulina platensis.
AB  - The role of light in the effect of salt stress on PSII photochemistry in the
      cyanobacterium Spirulina platensis grown at 50 micromol m(-2) s(-1) was
      investigated. The time-course of changes in PSII photochemistry in response to
      high salinity (0.8 M NaCl) incubated in the dark and at 30, 50 and 100 micromol
      m(-2) s(-1) was composed of two phases. The first phase, which was independent of
      light, was characterized by a rapid decrease (20-50%) in the maximal efficiency
      of PSII photochemistry (F:(v)/F:(m)), the efficiency of excitation energy capture
      by open PSII reaction centres (F(1)(v)/F(1)(m)), photochemical quenching (q(P)),
      and the quantum yield of PSII electron transport (Phi(PSII)) in the first 15 min,
      followed by a recovery of up to about 86-92% of their initial levels after 4 h of
      incubation. The second phase took place after 4 h, in which a further decline in
      the above parameters occurred only in the light but not in the dark, reaching
      levels as low as 32-56% of their initial levels after 12 h. Moreover, the higher
      incubation light intensity, the greater the decrease in the above parameters. At
      the same time, Q(B)-non-reducing PSII reaction centres increased significantly in
      the first 15 min and then recovered to the initial level during the first phase,
      but increased again in the light in the second phase. Photosynthetic oxygen
      evolution activity decreased sharply by 70% in the first 5 min, and then kept
      largely constant until 12 h. The changes in oxygen evolution activity were
      independent of light intensity during both phases.

PMID- 10948218
TI  - Ozone impacts on allometry and root hydraulic conductance are not mediated by
      source limitation nor developmental age.
AB  - O(3)could reduce growth and carbohydrate allocation to roots by direct inhibition
      of photosynthesis and source strength. Alternatively, O(3) could reduce growth
      indirectly by inhibition of root hydraulic development through a primary lesion
      in carbohydrate translocation. Another alternative is that O(3) could slow the
      rate of plant development, only apparently altering carbohydrate allocation at a
      given plant age. Pima cotton (Gossypium barbadense L.) is used to address these
      possibilities, and four hypotheses were tested/ (1) O(3) exposure reduces leaf
      pools of soluble sugars; (2) pruning leaf area and reducing source strength to
      match that of O(3)-treated plants reproduces O(3)-effects; (3) pruning lower leaf
      area more closely reproduces O(3) effects than pruning upper leaf area; and (4)
      manipulating plant age and thereby plant size to match O(3)-treated plants
      reproduces O(3)-effects. All were falsified. Soluble sugars did not decline.
      Pruning upper and lower leaves and manipulating plant age all reduced biomass and
      leaf area similarly to O(3)-exposure, but neither reproduced O(3) effects on
      biomass allocation nor root function. It is concluded that O(3) induces an
      allometric shift in carbohydrate allocation that is not mediated by
      photosynthetic inhibition nor by alteration of developmental age. Effects of O(3)
      could be mediated by direct effects on phloem loading, with consequent inhibition
      of translocation to roots and root system development.

PMID- 10948219
TI  - Radial transport of abscisic acid conjugates in maize roots: its implication for
      long distance stress signals.
AB  - Conjugated, alkaline hydrolysable ABA (predominantly abscisic acid glucose ester,
      ABA-GE), which is transported in the xylem from roots to shoots of Zea mays L.
      plants, has its origin in the root symplast rather than from soil, although it
      was detectable in soil solution with concentrations up to 30 nM. External ABA
      glucose ester cannot be dragged with the water flow across the exodermis and the
      endodermis because of its hydrophobic properties. Experimental evidence is
      presented that enzymes in the cortical apoplast cleave ABA-GE thus releasing ABA
      from its conjugates. Liberated ABA can then be translocated apoplastically and
      symplastically to the xylem vessels. Endogenous ABA-GE can be released from
      isolated cortical and stelar tissues to the surrounding media, with rates that
      are up to 5-fold higher from stelar tissues than those from cortical tissues.
      Release of ABA-GE is highest under conditions of inhibited ABA-metabolism.

PMID- 10948222
TI  - A method for expression cloning of transporter genes by screening yeast for
      uptake of radiolabelled substrate.
AB  - A method has been developed for the cloning of plasma membrane transporters by
      screening yeast transformed with a cDNA library for the accumulation of
      radiolabelled substrate. The applicability of the method is demonstrated by
      cloning the amino acid permease AAP1. A yeast mutant defective in proline uptake
      was transformed with an Arabidopsis thaliana cDNA library and plated on medium
      supplemented with L-[U-(14)C]proline. Yeast colonies accumulating radiolabelled
      proline were identified by autoradiography. The plasmids of these colonies were
      reintroduced into the yeast mutant and restoration of proline uptake was
      confirmed by L-[U-(14)C]proline uptake measurements. Whereas cloning of
      transporters by functional complementation requires that the substrate taken up
      is metabolized by yeast to promote growth, the method described here can be used
      to isolate transporters of substrates which are not metabolized. The method has
      great potential for the isolation of transporters of various substrates such as
      secondary plant products.

PMID- 10948220
TI  - Extracellular beta-glucosidase activity in barley involved in the hydrolysis of
      ABA glucose conjugate in leaves.
AB  - Abscisic acid conjugate concentrations increased in barley xylem sap under
      salinity, whereas it remained at a low level in the intercellular washing fluid
      (IWF) of barley primary leaves (Hordeum vulgare cv. Gerbel). Here it is shown
      that IWF contains beta-glucosidase activity which releases abscisic acid (ABA)
      from the physiologically inactive ABA-glucose conjugate pool in the leaf
      apoplast. The following data support this conclusion and give the first
      biochemical and physiological characterization of the extracellular glucosidase
      activity in barley. Free ABA was released by the incubation of ABA glucose ester
      with IWF. The product exhibited the retention time of authentic ABA upon
      separation by thin layer chromatography and was identified by ABA-ELISA. p
      Nitrophenol-beta-D-glucopyranoside (pNPG) was used as the substrate for beta
      glucosidases. The K(M)(pNPG) was 1.8 mmol l(-1). The activity was affected by ABA
      glucopyranoside in a competitive type of inhibition with a K(I) of 400 micromol
      l(-1). Various hormone conjugates were compared with respect to their inhibitory
      effect on beta-glucosidase activity. Inhibition was highest for the ABA
      glucopyranoside and the zeatin riboside, but insignificant for ABA methyl ester
      and zeatin-9-beta-D-glucoside. The specific activity of the beta-glucosidase was
      16-fold greater in IWF as compared to crude leaf extracts confirming its
      extracellular compartmentation. The activity of beta-glucosidase was strongly
      increased after growth in hydroponic medium supplemented with NaCl. The data
      support the hypothesis that the glucose conjugate is a long-distance transport
      form of ABA.

PMID- 10948221
TI  - Effects of zinc and influence of Acremonium lolii on growth parameters,
      chlorophyll a fluorescence and antioxidant enzyme activities of ryegrass (Lolium
      perenne L. cv Apollo).
AB  - The effects of zinc on growth, mineral content, chlorophyll a fluorescence, and
      detoxifying enzyme activity (ascorbate peroxidase (APX), EC 1.11.1.11; superoxide
      dismutase (SOD), EC 1.15.1.1) of ryegrass infected or not by Acremonium lolii,
      and treated with nutrient solution containing 0-50 mM ZnSO(4) were studied. The
      introduction of zinc induces stress with a decrease in growth at 1, 5 and 10 mM
      ZnSO(4) and a cessation of growth at 50 mM ZnSO(4), in ryegrass plants infected
      by A. lolii or not. This decrease in growth may be due to an accumulation of zinc
      in leaves. Nevertheless, symbiotic plants showed higher values in tiller number,
      an advantage conferred by the fungus. After 24 d of Zn exposure, leaf fresh
      weights and leaf water content were lower in plants growing with Zn in the
      culture medium and no advantage was conferred by the fungus to its host. An
      increase in Zn supply resulted in a decrease of the Ca, K, Mg, and Cu content of
      the leaves, a reduction in the quantum yield of electron flow throughout
      photosystem II (DeltaF/F(1)(m))and a lowering of the efficiency of photosynthetic
      energy conversion (F(v)/F(m)), compared to control plants. To counter this zinc
      stress, detoxifying enzymes APX and SOD increased (100%) when Zn reached the
      value of 50 mM in the nutrient solution. At 10 mM ZnSO(4), the presence of the
      fungus in the plant led to an increase in the threshold toxicity of plants to
      zinc by a diminution of APX activity.

PMID- 10948223
TI  - A new method for on-line measurement of diurnal change in potato tuber growth
      under controlled environments.
AB  - An on-line laser micrometer system was applied to measurement of diurnal change
      in potato (Solanum tuberosum L.) tuber growth. Diameters of the potato tuber were
      scanned by moving a laser micrometer along the longitudinal axis of the tuber at
      constant speed, and tuber volume was evaluated as an aggregate of thin discs. A
      single potato tuber, without competitive sink tubers in the plant, was grown in
      controlled air at 20 degrees C and 80% RH, and tuber volume was measured at 30
      min intervals. During the growth experiment, the potato tuber increased in size
      without any inhibitory effect of periodical laser beam irradiation. Greatest
      expansion generally occurred during the early night, and transient contraction of
      the tuber occurred at the beginning of the light period.

PMID- 10948224
TI  - A new FISH protocol with increased sensitivity for physical mapping with short
      probes in plants.
AB  - Fluorescence in situ hybridization (FISH) is a well-established technique used
      for the detection of specific DNA regions, that has been applied to interphase
      nuclei, pachytene and metaphase chromosomes as well as to extended DNA fibres.
      This technique allows the physical mapping of specific DNA sequences both on
      individual chromosomes and extended fibres. A new FISH protocol is described here
      that enhances the sensitivity of the method. Probes for small unique DNA
      sequences of less than 2 kb give high signal-to-noise ratio with this method, and
      can be visualized easily by means of conventional fluorescence microscopy.

PMID- 10948225
TI  - Polarity and signalling in plant embryogenesis.
AB  - The establishment of the apical-basal axis is a critical event in plant
      embryogenesis, evident from the earliest stages onwards. Polarity is evident in
      the embryo sac, egg cell, zygote, and embryo-suspensor complex. In the embryo
      proper, two functionally distinct meristems form at each pole, through the
      localized expression of key genes. A number of mutants, notably of the model
      genetic organism Arabidopsis thaliana, have revealed new gene functions that are
      required for patterning of the apical-basal axis. There is now increasing
      evidence that two particular modes of signalling, via auxin and cell wall
      components, play important roles in co-ordinating the gene expression programmes
      that define determinative roles in the establishment of polarity.

PMID- 10948226
TI  - Cysteine synthase (O-acetylserine (thiol) lyase) substrate specificities classify
      the mitochondrial isoform as a cyanoalanine synthase.
AB  - A cyanoalanine synthase and two isoforms (A, cytosolic and B, chloroplastic) of
      cysteine synthase (O:-acetylserine (thiol) lyase) were isolated from spinach. N
      terminal amino acid sequence analysis of the cyanoalanine synthase gave 100%
      homology for the determined 12 residues with a published sequence for the
      mitochondrial cysteine synthase isoform. All three enzymes catalysed both the
      cysteine synthesis and cyanoalanine synthesis reactions, although with different
      efficiencies. Michaelis-Menten kinetics were observed for all three enzymes when
      substrate saturation experiments were performed varying O:-acetylserine,
      chloroalanine and cysteine. Negative co-operative kinetics were observed for
      cysteine synthases A and B when substrate saturation experiments were performed
      varying sulphide and cyanide, compared with the Michaelis-Menten kinetics
      observed for cyanoalanine synthase. The exception was negative co-operativity
      observed towards sulphide for cyanoalanine synthase with O:-acetylserine as co
      substrate. The optimum sulphide concentration was dependent on the alanyl co
      substrate used. The amino acid sequence similarity places these three enzymes in
      the same gene family, and whilst the close kinetic similarities support this,
      they also indicate distinct roles for the isoforms.

PMID- 10948227
TI  - Changes in gene expression in the leafy cotyledon1 (lec1) and fusca3 (fus3)
      mutants of Arabidopsis thaliana L.
AB  - Arabidopsis thaliana L. leafy cotyledon1 (lec1) and fusca3 (fus3) mutants show
      multiple phenotypic defects during seed development. In this report the effects
      of these mutations are examined at the molecular level. The patterns of protein
      accumulation in lec1 and fus3 seeds are severly altered. In lec1 seeds the steady
      state mRNA levels of several late embryogenesis genes were reduced. Different
      patterns of expression were observed, indicating the occurrence of several
      regulatory pathways. The effect of lec1 mutations on the expression of the late
      embryogenesis abundant AtEm1 gene was examined in detail. In lec1-1 seeds, the
      AtEm1 gene was expressed at a higher level than in the wild type and earlier in
      development. The activity of an AtEm1 promoter/beta-glucuronidase reporter gene
      construct in transgenic A. thaliana plants was studied. Changes in promoter
      activity in lec1-1 with respect to wild-type seeds were correlated with changes
      in corresponding mRNA steady-state levels. fus3-2 mutation produced similar
      changes in AtEm1 promoter activity as lec1-1, which is consistent with the
      hypothesis that LEC1 and FUS3 might act in the same regulatory pathway.
      Transgenic analysis using 5'-promoter deletions demonstrated that at least two
      regions of AtEm1 gene promoter interact with the LEC1-dependent transcriptional
      regulatory pathway. In spite of expression of the AtEm1 promoter and accumulation
      of AtEm1 mRNA, the corresponding Em1 protein does not accumulate in lec1-1 seeds.
      The ABA inducibility of the AtEm1 promoter was not affected by the lec1 mutation.

PMID- 10948228
TI  - Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver
      somniferum l., and California poppy, Eschscholzia californica cham., root
      cultures.
AB  - An efficient protocol for the establishment of transgenic opium poppy (Papaver
      somniferum L.) and California poppy (Eschscholzia californica Cham.) root
      cultures using A. grobacterium rhizogenes is reported. Five strains of A.
      rhizogenes were tested for their ability to produce hairy roots on wounded opium
      poppy seedlings and California poppy embryogenic calli. Three of the strains
      induced hairy root formation on both species, whereas two others either caused
      the growth of tumorigenic calli or produced no response. To characterize the
      putative transgenic roots further, explant tissues were co-cultivated with the
      most effective A: rhizogenes strain (R1000) carrying the pBI121 binary vector.
      Except for the co-cultivation medium, all formulations included 50 mg l(-1)
      paromomycin to select for transformants and 200 mg l(-1) timentin to eliminate
      the Agrobacterium. Four weeks after infection, paromomycin-resistant roots
      appeared on 92-98% of explants maintained on hormone-free medium. Isolated hairy
      roots were propagated in liquid medium containing 1.0 mg l(-1) indole-3-acetic
      acid to promote rapid growth. Detection of the neomycin phosphotransferase gene,
      high levels of beta-glucuronidase (GUS) transcripts and enzyme activity, and GUS
      histochemical localization confirmed the integrative transformation of root
      cultures. Transgenic roots grew faster than wild-type roots, and California poppy
      roots grew more rapidly than those of opium poppy. With the exception of a less
      compact arrangement of epidermal cells and more root hairs, transformed roots of
      both species displayed anatomical features and benzylisoquinoline alkaloid
      profiles that were virtually identical to those of wild-type roots. Transgenic
      root cultures of opium poppy and California poppy are a simple, reliable and well
      defined model system to investigate the molecular and metabolic regulation of
      benzylisoquinoline alkaloid biosynthesis, and to evaluate the genetic engineering
      potential of these important medicinal plants.

PMID- 10948229
TI  - Two cDNAs representing alleles of the nitrate reductase gene of potato (Solanum
      tuberosum L. cv. Desiree): sequence analysis, genomic organization and
      expression.
AB  - Two, different, full-length cDNAs, StNR2 and StNR3, of 3049 and 3066 nucleotides,
      respectively, were isolated from a Solanum tuberosum L. cv. Desiree leaf cDNA
      library by an RT-PCR approach. Conceptual translation of the longest open reading
      frame of each cDNA showed that they could encode a protein of 911 amino acids in
      each case with an M(r) of 102.6 and 102.5 kDa, respectively, and with 99.7%
      identity with each other. The cDNAs have a high degree of sequence similarity
      with all higher plant nitrate reductases (NRs) and possess structural
      characteristics expected of NADH-NR proteins, consistent with enzyme activity
      data. Southern analysis of genomic DNA suggested the presence of a single NR gene
      in the potato genome whilst studies using the mapping population F1840, and the
      full-length StNR2 cDNA as hybridization probe, identified a single NR locus
      within the potato genome that is located on chromosome XI. The two cDNAs
      identified here are probably derived from two transcribing alleles of this single
      gene. Distribution of total NR transcript and of NADH-NR activity, in different
      organs of compost-grown plants, depended on the level of nitrate supplied: at low
      nitrate level transcript and activity were detected only in leaf and stem tissue
      whilst at high nitrate level they could also be detected in root and stolon. An
      RT-PCR approach was used to differentiate between the transcripts derived from
      the two identified alleles and to show that the pattern of transcription of the
      two identified alleles of the potato nia gene, in the organs studied, is the
      same.

PMID- 10948231
TI  - Photosynthetic carbohydrate metabolism in wheat (Triticum aestivum L.) leaves:
      optimization of methods for determination of fructose 2, 6-bisphosphate.
AB  - The accurate measurement of fructose 2,6-bisphosphate from plants such as wheat
      is fraught with difficulty. Extraction and assay methods for fructose 2,6
      bisphosphate that give near 100% recovery of the metabolite, and a linear
      response with volume have therefore been developed for extracts prepared from
      wheat leaves of different ages. Amounts of fructose 2,6-bisphosphate in different
      regions of leaves generally showed a positive correlation with chlorophyll
      content. Measurements of sucrose and starch in third leaves harvested at
      different times of the diurnal cycle demonstrated that sucrose is the major form
      in which photosynthate is stored in the leaf, but starch can account for up to
      about 30% of the stored carbohydrate. Virtually all of the carbohydrate
      accumulated as starch and sucrose during the day was degraded at night. Amounts
      of fructose 2,6-bisphosphate were generally lower in extracts prepared from
      leaves harvested in the light than in the dark. Additionally, there was no change
      in either the amount of fructose 2, 6-bisphosphate or the ratio of sucrose to
      starch in samples prepared from leaves harvested at different times of the day.
      These results are broadly consistent with a role for fructose 2,6-bisphosphate in
      the regulation of sucrose synthesis and the partitioning of carbohydrate between
      sucrose and starch in wheat leaves.

PMID- 10948230
TI  - A nitric oxide burst precedes apoptosis in angiosperm and gymnosperm callus cells
      and foliar tissues.
AB  - Leaves and callus of Kalanchoe daigremontiana and Taxus brevifolia were used to
      investigate nitric oxide-induced apoptosis in plant cells. The effect of nitric
      oxide (NO) was studied by using a NO donor, sodium nitroprusside (SNP), a nitric
      oxide-synthase (NOS) inhibitor, N:(G)-monomethyl-L-arginine (NMMA), and
      centrifugation (an apoptosis-inducing treatment in these species). NO production
      was visualized in cells and tissues with a specific probe, diaminofluorescein
      diacetate (DAF-2 DA). DNA fragmentation was detected in situ by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. In
      both species, NO was detected diffused in the cytosol of epidermal cells and in
      chloroplasts of guard cells and leaf parenchyma cells. Centrifugation increased
      NO production, DNA fragmentation and subsequent cell death by apoptosis. SNP
      mimicked centrifugation results. NMMA significantly decreased NO production and
      apoptosis in both species. The inhibitory effect of NMMA on NO production
      suggests that a putative NOS is present in Kalanchoe and Taxus cells. The present
      results demonstrated the involvement of NO on DNA damage leading to cell death,
      and point to a potential role of NO as a signal molecule in these plants.

PMID- 10948232
TI  - Effluxes of solutes from developing seed coats of Phaseolus vulgaris L. and Vicia
      faba l.: locating the effect of turgor in a coupled chemiosmotic system.
AB  - Cells lining the developing seed coats of legumes efflux photosynthates (mostly
      sucrose) and salts (mostly of potassium) into the apoplast for uptake by the
      developing embryo. These effluxes increase transiently in response to an increase
      in turgor in the effluxing cells. Detached coats of developing seed of P.
      haseolus vulgaris and Vicia faba were used to study the effects of turgor on the
      rates of efflux, on the membrane potential difference and on the membrane pH
      difference, using a number of inhibitors and agents which might affect signal
      cascades involving cytoplasmic calcium concentration. Effluxes were measured by
      measuring the concentrations of solutes of interest in solution samples placed in
      halves of detached seed coats, the paired halves serving as control and treated
      sample where appropriate. It is shown that a number of substances affect sucrose
      and potassium effluxes differently, and that hypo-osmotic shock depolarizes the
      efflux cells and acidifies the cytoplasm (in P. vulgaris). It is concluded that
      sucrose and potassium effluxes, although both are increased by an increase in
      turgor, are affected by different signal pathways. Further, it is also concluded
      that the signal that increases the rates of both sucrose efflux (via sucrose
      proton antiport) and proton pump acts directly on the antiporter rather than on
      the pump. There are interesting parallels and contrasts between these processes
      and those in plants such as the charophyte Lamprothamnium after hypo-osmotic
      shock.

PMID- 10948233
TI  - Effects of aluminium on the growth and mineral composition of Betula pendula
      Roth.
AB  - Aluminium (Al) is rhizotoxic and is often present in acidic soils at activities
      high enough to inhibit root elongation. The objectives of the present study were
      to assess the level of Al tolerance in different races of Betula pendula Roth
      (Silver Birch) and to investigate how growth and nutrient acquisition were
      affected by Al. A solution culture technique was employed which simulated natural
      soil solutions. Aluminium at low concentrations (2 and 5 mg l(-1)), enhanced the
      growth of two races of B. pendula originating from soils poor in Al (FM and KP).
      In contrast, Al, at all concentrations tested, inhibited growth in an Al
      sensitive race (KR) whose provenance was a calcareous soil. At concentrations
      >/=10 mg l(-1), Al reduced growth in FM and KP races, while growth increased with
      increasing Al (up to 25 mg l(-1)) in the Al-tolerant, SMM, race. Aluminium
      altered both root and leaf architecture. Low Al concentrations (<5 mg l(-1))
      significantly increased leaf expansion, and high concentrations (>25 mg l(-1))
      reduced leaf expansion. In the Al-sensitive race, KR, there was a loss of apical
      dominance, and both lateral and primary roots were stunted and swollen, with
      increasing Al concentrations. These results demonstrated pronounced racial
      differences in tolerance to Al by B. pendula that could be predicted from the
      soil environment of each race.

PMID- 10948234
TI  - The influence of secondary senescence processes within the culm of a
      pseudoviviparous grass (Poa alpina var. vivipara L.) on the supply of water to
      propagules.
AB  - An anatomical investigation of the culm of pseudoviviparous alpine meadow grass
      (Poa alpina var. vivipara L.) revealed that transpiration flow, as delimited by
      Lucifer Yellow tracer dye, was maintained despite advanced senescence (as
      evidenced by loss of chlorophyll and chloroplasts), with leafy spikelets driving
      transpiration flow. Transpiration flow was not hindered by cavitation or tylosis
      in older culms, the low frequencies of these senescence processes being bypassed
      via nodal plexi. Despite this, water content of plantlets declined over time and
      water stress became apparent, suggesting that water supply via the determinate
      culm was not sufficient for the increasing transpirational demand of
      indeterminate plantlets. The implications of declining water content on the
      biomechanical properties of the culm, and concomitant limitations on the
      pseudoviviparous reproductive strategy, are discussed. Nomenclature of grass
      follows Hubbard.

PMID- 10948235
TI  - Leaf age-dependent differences in sulphur assimilation and allocation in poplar
      (Populus tremula x P. alba) leaves.
AB  - 35S-sulphate was flap-fed to poplar leaves of different leaf development stages -
      young developing, expanding, mature, and old mature poplar leaves. (35)S-sulphate
      was taken up independent of the leaf development stage. Whereas young development
      leaves did not export the (35)S taken up, export increased with increasing leaf
      development stage. Expanding leaves allocated the exported (35)S mainly into
      apical tree parts (73-87%) and only to a minor extent (13-27%) in basipetal
      direction. Neither lower trunk sections nor the roots were sinks for the exported
      (35)S. Expanding and developing leaves, but not the shoot apex, were the main
      sinks for the (35)S allocated in apical direction. In contrast, mature and old
      mature leaves exported the (35)S taken up mainly in basipetal direction (65-82%)
      with the roots constituting the main sinks. The (35)S allocated into apical tree
      parts was found in expanding and developing leaves, but only to a minor extent in
      the shoot apex. Apical allocated (35)S was identified as sulphate. Apparently the
      demand of young developing leaves for reduced sulphur was not fulfilled by mature
      leaves. Therefore, reduced sulphur for growth and development of young developing
      leaves must be supplied from other sources. In vitro activity of enzymes involved
      in assimilatory sulphate reduction was measured to investigate whether demand for
      reduced sulphur by young leaves is met by their own sulphate reduction. ATP
      sulphurylase and APS reductase activities were not significantly lower in
      developing than in mature leaves. Sulphite reductase and serine acetyltransferase
      activities were highest in developing leaves; O:-acetylserine (thiol) lyase
      activity was similar in all leaf developing stages. Apparently, young developing
      poplar leaves are able to produce their own reduced sulphur for growth and
      development. Whether other sources such as storage tissues and/or roots are
      involved in reduced sulphur supply to developing leaves remains to be elucidated.

PMID- 10948236
TI  - Respiratory costs and rate of protein turnover in the roots of a fast-growing
      (Dactylis glomerata L.) and a slow-growing (Festuca ovina L.) grass species.
AB  - Protein turnover is generally regarded as one of the most important maintenance
      processes in plants in terms of energy requirements. In this study, the
      contribution of protein turnover to the respiratory costs for maintenance in the
      roots of two grass species, the fast-growing D. actylis glomerata L. and the slow
      growing F. estuca ovina L., is evaluated. Plants were grown under controlled
      environment conditions in a nutrient solution to which NO(3)- was added at a
      relative addition rate of 0.2 and 0.1 mol N mol(-1) N already present in the
      plant d(-1) for D. glomerata and F. ovina, respectively, so as to obtain a steady
      exponential growth rate close to the plants' maximum relative growth rate. Pulse
      chase labelling with (14)C-leucine was used to determine the rate of protein
      turnover in the grass roots. The rate of turnover of the total protein pool did
      not differ significantly between the two species. The protein degradation
      constant in D. glomerata and F. ovina was 0.156 and 0.116 g protein g(-1) protein
      d(-1), respectively, which corresponds with a total protein half-life of 4 d and
      6 d. Assuming specific respiratory costs for protein turnover of 148 mmol ATP g(
      1) protein, the estimated respiratory costs for protein turnover in the roots
      were 2.8 and 2.4 mmol ATP g(-1) root DM d(-1) in D. glomerata and F. ovina,
      respectively. Both the fast- and the slow-growing grass spent between 22-30% of
      their daily ATP production for maintenance on protein turnover, which corresponds
      to 11-15% of the total root ATP production per day. Note that the data presented
      in this abstract are based on the assumption that 50% recycling of the (14)C
      labelled leucine took place in the roots of both grass species.

PMID- 10948238
TI  - Functional role of anthocyanins in the leaves of Quintinia serrata A. Cunn.
AB  - The protective functions that have been ascribed to anthocyanins in leaves can be
      performed as effectively by a number of other compounds. The possibility that
      anthocyanins accumulate most abundantly in leaves deficient in other
      phytoprotective pigments has been tested. Pigment concentrations and their
      histological distribution were surveyed for a sample of 1000 leaves from a forest
      population of Quintinia serrata, which displays natural polymorphism in leaf
      colour. Eight leaf phenotypes were recognized according to their patterns of red
      coloration. Anthocyanins were observed in almost all combinations of every leaf
      tissue, but were most commonly located in the vacuoles of photosynthetic cells.
      Red leaves contained two anthocyanins (Cy-3-glc and Cy-3-gal), epicuticular
      flavones, epidermal flavonols, hydroxycinnamic acids, chlorophylls, and
      carotenoids. Green leaves lacked anthocyanins, but had otherwise similar pigment
      profiles. Foliar anthocyanin levels varied significantly between branches and
      among trees, but were not correlated to concentrations of other pigments.
      Anthocyanins were most abundant in older leaves on trees under canopies with
      south-facing gaps. These data indicate that anthocyanins are associated with
      photosynthesis, but do not serve an auxiliary phytoprotective role. They may
      serve to protect shade-adapted chloroplasts from brief exposure to high intensity
      sunflecks.

PMID- 10948237
TI  - Nitrate reductases from leaves of Ricinus (Ricinus communis L.) and spinach
      (Spinacia oleracea L.) have different regulatory properties.
AB  - The activity of nitrate reductase (+Mg(2+), NR(act)) in illuminated leaves from
      spinach, barley and pea was 50-80% of the maximum activity (+EDTA, NR(max)).
      However, NR from leaves of Ricinus communis L. had a 10-fold lower NR(act), while
      NR(max) was similar to that in spinach leaves. The low NR(act) of Ricinus was
      independent of day-time and nitrate nutrition, and varied only slightly with leaf
      age. Possible factors in Ricinus extracts inhibiting NR were not found. NR(act)
      from Ricinus, unlike the spinach enzyme, was very low at pH 7.6, but much higher
      at more acidic pH with a distinct maximum at pH 6.5. NR(max) had a broad pH
      response profile that was similar for the spinach and the Ricinus enzyme.
      Accordingly, the Mg(2+)-sensitivity of NR from Ricinus was strongly pH-dependent
      (increasing sensitivity with increasing pH), and as a result, the apparent
      activation state of NR from a Ricinus extract varied dramatically with pH and
      Mg(2+)concentration. Following a light-dark transition, NR(act) from Ricinus
      decreased within 1 h by 40%, but this decrease was paralleled by NR(max). In
      contrast to the spinach enzyme, Ricinus-NR was hardly inactivated by incubating
      leaf extracts with ATP plus okadaic acid. A competition analysis with antibodies
      against the potential 14-3-3 binding site around ser 543 of the spinach enzyme
      revealed that Ricinus-NR contains the same site. Removal of 14-3-3 proteins from
      Ricinus-NR by anion exchange chromatography, activated spinach-NR but caused
      little if any activation of Ricinus-NR. It is suggested that Mg(2+)-inhibition of
      Ricinus-NR does not require 14-3-3 proteins. The rather slow changes in Ricinus
      NR activity upon a light/dark transient may be mainly due to NR synthesis or
      degradation.

PMID- 10948239
TI  - Exclusion of grass roots from soil organic layers by Calluna: the role of ericoid
      mycorrhizas.
AB  - The role of ericoid mycorrhizal colonization in competition between the dwarf
      shrub Calluna vulgaris and coarse grass Nardus stricta was investigated. Nardus
      was grown alone, or in competition with Calluna, in a layered organic/sand
      substrate with and without inoculation with the ericoid mycorrhizal endophyte
      Hymenoscyphus ericae, and with and without the addition of nitrogen. Root length
      and allocation between different substrate layers was assessed along with plant
      biomass, nutrient uptake and mycorrhizal colonization. Calluna was the superior
      competitor for nutrients, probably because of its ability to concentrate root
      growth in the upper organic layer. In the presence of Calluna both the absolute
      amount and proportion of Nardus root length in the organic layer were reduced,
      and this reduction was greatest when Calluna was mycorrhizal. The presence of
      ericoid mycorrhizal colonization did not reduce Nardus shoot nutrient content or
      concentration, suggesting that ericoid mycorrhizal suppression of Nardus growth
      was not due to nutrient competition: alternative mechanisms of interference are
      discussed.

PMID- 10948240
TI  - Antagonistic action of low-fluence and high-irradiance modes of response of
      phytochrome on germination and beta-mannanase activity in Datura ferox seeds.
AB  - Seed germination is often induced by a pulse of red light perceived by
      phytochrome and cancelled by a subsequent pulse of far-red light. When the pulse
      of red light is followed by several hours of darkness, a pulse of far-red light
      is no longer effective and prolonged far-red is necessary to block germination.
      The aim was to investigate whether the red light pulse and prolonged far-red
      light act on the same or different processes during germination of Datura ferox
      seeds. Forty-five hours after the inductive red light pulse, germination could
      not be blocked by one pulse or six hourly pulses of far-red light, but was
      significantly reduced by 6 h of continuous far-red light. The pulse of red light
      increased embryo growth potential and the activities of beta-mannanase and beta
      mannosidase extracted from the micropylar region of the endosperm. Continuous far
      red light had no effect on embryo growth potential or beta-mannosidase activity,
      but severely reduced the activity of beta-mannanase. The effect of far-red light
      had the features of a high-irradiance response of phytochrome. Both germination
      and beta-mannanase activity were restored by a pulse of red light given after the
      end of the continuous far-red treatment. It is concluded that the low-fluence
      response and the high-irradiance response modes of phytochrome have antagonistic
      effects on seed germination and that the control of beta-mannanase activity is
      one process where this antagonism is established.

PMID- 10948241
TI  - Comparative field water relations of three Mediterranean shrub species co
      occurring at a natural CO(2) vent.
AB  - Annual variations in the water relations and stomatal response of Erica arborea,
      Myrtus communis and Juniperus communis occurring at a natural CO(2) vent were
      analysed under Mediterranean field conditions. A distinct gradient of
      CO(2)concentration ([CO(2)]) exists between two sites near a natural CO(2)
      emitting vent, with higher [CO(2)] (700 micromol mol(-1)) in the proximity of the
      CO(2) spring. Plants at the CO(2) spring site have been growing for generations
      at elevated [CO(2)]. At both sites, maximum leaf conductance was related to
      predawn shoot water potential. The effects of water deficits during the summer
      drought were severe. Leaf conductance and water potential recovered after major
      rainfalls in September to predrought values. Strong relationships between leaf
      conductance, predawn water potential, and leaf-specific hydraulic resistance are
      consistent with the role of stomata in regulating plant water status.
      Considerable between-species variation in sensitivity of water potentials and
      stomatal characters to elevated [CO(2)] were observed. Common to all the shrubs
      were a reduction in leaf conductance and an increase in water potentials in
      response to elevated [CO(2)]. Elevated [CO(2)] decreased the sensitivity of leaf
      conductance to vapour pressure deficit. Morphological characters (including
      stomatal density and degree of sclerophylly) showed site-dependent variations,
      but degree and sign of such changes varied with the species and/or the season.
      Measurements of discrimination against (13)C provided evidence for long-term
      decreases of water use efficiency in CO(2) spring plants. Analysis of C isotope
      composition suggested that a downward adjustment of photosynthetic capacity may
      have occurred under elevated [CO(2)]. Elevated [CO(2)] effects on water relations
      and leaf morphology persisted in the long term, but the three shrubs growing in
      the same environment showed species-specific responses.

PMID- 10948242
TI  - Capillary electrophoresis for the determination of major amino acids and sugars
      in foliage: application to the nitrogen nutrition of Sclerophyllous species.
AB  - Amino acids and sugars are probably the most commonly measured solutes in plant
      fluids and tissue extracts. Chromatographic techniques used for the measurement
      of such solutes require complex derivatization procedures, analysis times are
      long and separate analyses are required for sugars and amino acids. Two methods
      were developed for the analysis of underivatized sugars and amino acids by
      capillary electrophoresis (CE). Separation of a range of sugars and amino acids
      was achieved in under 30 min, with good reproducibility and linearity. In
      general, there was close agreement between amino acid analyses by CE and HPLC
      with post-column derivatization. An alternative, more rapid method was optimized
      for the common neutral sugars. Separation of a mixture of fructose, glucose,
      sucrose, and fucose (internal standard) was achieved in less than 5 min. How the
      source of N applied (nitrate or ammonium) and its concentration (8.0 or 0.5 mM)
      affects the amino acid and sugar composition of leaves from Banksia grandis
      Willd. and Hakea prostrata R. Br. was investigated. The amino acid pool of
      Banksia and Hakea were dominated by seven amino acids (aspartic acid, glutamic
      acid, asparagine, glutamine, serine, proline, and arginine). Of these,
      asparagaine and glutamine dominated at low N-supply, whereas at high N-supply the
      concentration of arginine increased and dominated amino-N. Plants grown with
      nitrate had a greater concentration of proline relative to plants with ammonium.
      In Banksia the concentration of amides was greatest and arginine least with a
      nitrate N-source, whereas in Hakea amides were least and arginine greatest with
      nitrate N-source. The concentration of sugars was greater in Banksia than Hakea
      and in both species at greater N-supply.

PMID- 10948243
TI  - Changes in abscisic acid content and embryo sensitivity to (+)-abscisic acid
      during the termination of dormancy of yellow cedar seeds.
AB  - Yellow cedar seeds are dormant at maturity. The abscisic acid (ABA) content of
      the embryo (but not the megagametophyte) decreased approximately 2-fold following
      exposure of seeds to a dormancy-breaking treatment; this process was also
      accompanied by a 10-fold lowered sensitivity of the embryo to S:-(+)-ABA. A
      decline in ABA within the seed is not sufficient for dormancy breakage; reduced
      embryo sensitivity to ABA is also required.

PMID- 10948244
TI  - Isolation of cDNA clones corresponding to genes expressed during fruit ripening
      in Japanese pear (Pyrus pyrifolia Nakai): involvement of the ethylene signal
      transduction pathway in their expression.
AB  - Thirty cDNA clones of genes corresponding to mRNAs up-regulated during fruit
      ripening of Japanese pear (Pyrus pyrifolia Nakai cv. Kikusui) were obtained by
      differential screening of a ripe fruit cDNA library. All of these cDNAs were
      sequenced and gathered into 11 non-redundant groups after database searches.
      These clones represented genes associated with stress responses, protein
      catabolism or pathogenesis. The accumulation of transcripts of 3 out of 11 genes
      was inhibited by 1-methylcyclopropene (MCP), an inhibitor of ethylene action.

PMID- 10948245
TI  - Sequence analysis of the vir-region from Agrobacterium tumefaciens octopine Ti
      plasmid pTi15955.
AB  - The nucleotide sequence of 42 775 bp of the vir-region from the Agrobacterium
      tumefaciens octopine Ti plasmid pTi15955 is reported here. Although the
      nucleotide sequences of several parts of this region from this or closely related
      plasmids have been published previously, the present work establishes for the
      first time the complete arrangement of all the essential virulence genes and
      their intergenic regions of an octopine Ti plasmid. The disruption of some of the
      intergenic areas by insertion (IS) elements is typical for the octopine Ti
      plasmids. Several new ORFs were identified, including ORFs immediately downstream
      of virD4 and virE2, which probably represent new genes involved in virulence.

PMID- 10948246
TI  - Acyltransferases in protease's clothing.

PMID- 10948247
TI  - Prenylation of the floral transcription factor APETALA1 modulates its function.
AB  - The Arabidopsis MADS box transcription factor APETALA1 (AP1) was identified as a
      substrate for farnesyltransferase and shown to be farnesylated efficiently both
      in vitro and in vivo. AP1 regulates the transition from inflorescence shoot to
      floral meristems and the development of sepals and petals. AP1 fused to green
      fluorescent protein (GFP) retained transcription factor activity and directed the
      expected terminal flower phenotype when ectopically expressed in transgenic
      Arabidopsis. However, ap1mS, a farnesyl cysteine-acceptor mutant of AP1, as well
      as the GFP-ap1mS fusion protein failed to direct the development of compound
      terminal flowers but instead induced novel phenotypes when ectopically expressed
      in Arabidopsis. Similarly, compound terminal flowers did not develop in era1-2
      transformants that ectopically expressed AP1. Together, the results demonstrate
      that AP1 is a target of farnesyltransferase and suggest that farnesylation alters
      the function and perhaps specificity of the transcription factor.

PMID- 10948248
TI  - Functional requirement of plant farnesyltransferase during development in
      Arabidopsis.
AB  - Arabidopsis era1 was identified as an abscisic acid-hypersensitive mutant caused
      by disruptions or deletions of the gene for the beta subunit (AtFTB) of
      farnesyltransferase (FTase). The heterodimeric enzyme catalyzes the covalent
      attachment of the 15-carbon farnesyl diphosphate to the C terminus of regulatory
      proteins and is essential for growth in yeast. The first disruption of FTB in a
      multicellular context revealed several developmental and growth regulatory
      processes that require the function of FTase. The lack of FTase activity in the
      Arabidopsis era1-2 FTB deletion mutant resulted in enlarged meristems and organs,
      supernumerary organs in floral whorls, arrested development of axillary
      meristems, late flowering, and homeotic transformations of flowers.
      Complementation of era1-2 with LeFTB, the tomato gene for the beta subunit of
      FTase, restored a normal phenotype and confirmed that the lesion is in AtFTB
      alone. The effect of this lesion on control of meristem size and on developmental
      processes suggests the involvement of regulatory proteins that require
      farnesylation for their function. At least three distinct processes that require
      the function of FTase were identified: regulation of cellular differentiation in
      the meristems, meristem maintenance, and regulation of flower development.
      Together, these results provide a basis for future studies on the involvement of
      FTase in specific developmental processes and for structure-function analysis of
      FTase in vivo.

PMID- 10948249
TI  - Pea compound leaf architecture is regulated by interactions among the genes
      UNIFOLIATA, cochleata, afila, and tendril-lessn.
AB  - The compound leaf primordium of pea represents a marginal blastozone that
      initiates organ primordia, in an acropetal manner, from its growing distal
      region. The UNIFOLIATA (UNI) gene is important in marginal blastozone maintenance
      because loss or reduction of its function results in uni mutant leaves of reduced
      complexity. In this study, we show that UNI is expressed in the leaf blastozone
      over the period in which organ primordia are initiated and is downregulated at
      the time of leaf primordium determination. Prolonged UNI expression was
      associated with increased blastozone activity in the complex leaves of afila
      (af), cochleata (coch), and afila tendril-less (af tl) mutant plants. Our
      analysis suggests that UNI expression is negatively regulated by COCH in stipule
      primordia, by AF in proximal leaflet primordia, and by AF and TL in distal and
      terminal tendril primordia. We propose that the control of UNI expression by AF,
      TL, and COCH is important in the regulation of blastozone activity and pattern
      formation in the compound leaf primordium of the pea.

PMID- 10948250
TI  - Cloning of the SNG1 gene of Arabidopsis reveals a role for a serine
      carboxypeptidase-like protein as an acyltransferase in secondary metabolism.
AB  - Serine carboxypeptidases contain a conserved catalytic triad of serine,
      histidine, and aspartic acid active-site residues. These enzymes cleave the
      peptide bond between the penultimate and C-terminal amino acid residues of their
      protein or peptide substrates. The Arabidopsis Genome Initiative has revealed
      that the Arabidopsis genome encodes numerous proteins with homology to serine
      carboxypeptidases. Although many of these proteins may be involved in protein
      turnover or processing, the role of virtually all of these serine
      carboxypeptidase-like (SCPL) proteins in plant metabolism is unknown. We
      previously identified an Arabidopsis mutant, sng1 (sinapoylglucose accumulator
      1), that is defective in synthesis of sinapoylmalate, one of the major
      phenylpropanoid secondary metabolites accumulated by Arabidopsis and some other
      members of the Brassicaceae. We have cloned the gene that is defective in sng1
      and have found that it encodes a SCPL protein. Expression of SNG1 in Escherichia
      coli demonstrates that it encodes sinapoylglucose:malate sinapoyltransferase, an
      enzyme that catalyzes a transesterification instead of functioning like a
      hydrolase, as do the other carboxypeptidases. This finding suggests that SCPL
      proteins have acquired novel functions in plant metabolism and provides an
      insight into the evolution of secondary metabolic pathways in plants.

PMID- 10948251
TI  - Molecular analysis of the SCARECROW gene in maize reveals a common basis for
      radial patterning in diverse meristems.
AB  - Maize and Arabidopsis root apical meristems differ in several aspects of their
      radial organization and ontogeny. Despite the large evolutionary distance and
      differences in root radial patterning, analysis of the putative maize ortholog of
      the Arabidopsis patterning gene SCARECROW (SCR) revealed expression localized to
      the endodermis, which is similar to its expression in Arabidopsis. Expression in
      maize extends through the quiescent center, a population of mitotically inactive
      cells formerly thought to be undifferentiated and to lack radial pattern
      information. Zea mays SCARECROW (ZmSCR), the putative maize SCR ortholog, was
      used as a molecular marker to investigate radial patterning during regeneration
      of the root tip after either whole or partial excision. Analysis of the dynamic
      expression pattern of ZmSCR as well as other markers indicates the involvement of
      positional information as a primary determinant in regeneration of the root
      radial pattern.

PMID- 10948252
TI  - Evidence for a role of the N terminus and leucine-rich repeat region of the Mi
      gene product in regulation of localized cell death.
AB  - The tomato Mi gene confers resistance against root-knot nematodes and potato
      aphids. Chimeric constructs of the functional gene, Mi-1. 2, with a homolog, Mi
      1.1, were produced, and their phenotypes were examined in Agrobacterium
      rhizogenes-transformed roots. Exchange of the leucine-rich repeat (LRR) region of
      Mi-1.1 into Mi-1.2 resulted in the loss of ability to confer nematode resistance,
      as did substitution of a 6-amino acid sequence from the Mi-1.1 LRR into Mi-1.2.
      Introduction of the Mi-1.2 LRR-encoding region into Mi-1.1 resulted in a lethal
      phenotype, as did substitution of the fragment encoding the N-terminal 161 amino
      acids of Mi-1.1 into Mi-1.2. Transient expression of the latter two chimeric
      constructs in Nicotiana benthamiana leaves produced localized cell death. The
      cell death caused by the N-terminal exchange was suppressed by coinfiltration
      with a construct expressing the N-terminal 161 amino acids of Mi-1.2. The
      phenotypes of these and other constructs indicate that the LRR region of Mi-1.2
      has a role in signaling localized cell death and that the N-terminal 161 amino
      acids have a role in regulating this death.

PMID- 10948253
TI  - A mitogen-activated protein kinase kinase required for induction of cytokinesis
      and appressorium formation by host signals in the conidia of Colletotrichum
      gloeosporioides.
AB  - Differentiation of fungal conidia of phytopathogens into the infection structure,
      appressorium, requires contact with a hard surface and host signals. The
      molecular signaling involved in the induction of this differentiation is poorly
      understood. We report the cloning of a mitogen-activated protein kinase kinase
      (MEK), CgMEK, from Colletotrichum gloeosporioides and its role in the induction
      of these developmental processes involved in pathogenesis. Disruption of CgMEK1
      resulted in the loss of its ability to form appressoria in response to the host's
      signals and a loss of virulence. Results of confocal microscopic examination of
      germinating conidia of the gene-disrupted mutants were similar to those for wild
      type conidia treated with an MEK inhibitor, suggesting that CgMEK1 is involved in
      two developmental processes in the differentiation into appressorium: (1)
      polarized cell division, with the preferential increase in F-actin in one of the
      daughter nuclei after nuclear division and the formation of septum; and (2)
      differentiation of the germ tube into an appressorium. CgMEK1 is required for the
      differentiation.

PMID- 10948254
TI  - A new subfamily of sucrose transporters, SUT4, with low affinity/high capacity
      localized in enucleate sieve elements of plants.
AB  - A new subfamily of sucrose transporters from Arabidopsis (AtSUT4), tomato
      (LeSUT4), and potato (StSUT4) was isolated, demonstrating only 47% similarity to
      the previously characterized SUT1. SUT4 from two plant species conferred sucrose
      uptake activity when expressed in yeast. The K(m) for sucrose uptake by AtSUT4 of
      11.6 +/- 0.6 mM was approximately 10-fold greater than for all other plant
      sucrose transporters characterized to date. An ortholog from potato had similar
      kinetic properties. Thus, SUT4 corresponds to the low-affinity/high-capacity
      saturable component of sucrose uptake found in leaves. In contrast to SUT1, SUT4
      is expressed predominantly in minor veins in source leaves, where high-capacity
      sucrose transport is needed for phloem loading. In potato and tomato, SUT4 was
      immunolocalized specifically to enucleate sieve elements, indicating that like
      SUT1, macromolecular trafficking is required to transport the mRNA or the protein
      from companion cells through plasmodesmata into the sieve elements.

PMID- 10948255
TI  - AINTEGUMENTA promotes petal identity and acts as a negative regulator of AGAMOUS.
AB  - The Arabidopsis AINTEGUMENTA (ANT) gene has been shown previously to be involved
      in ovule development and in the initiation and growth of floral organs. Here, we
      show that ANT acts in additional processes during flower development, including
      repression of AGAMOUS (AG) in second whorl cells, promotion of petal epidermal
      cell identity, and gynoecium development. Analyses of ap2-1 ant-6 double mutants
      reveal that ANT acts redundantly with AP2 to repress AG in second whorl cells.
      The abaxial surface of ant petals contains features such as stomata and
      elongated, interdigitated cells that are not present on wild-type petals. The
      loss of petal identity in these second whorl cells does not result from ectopic
      AG expression, suggesting that ANT acts in a pathway promoting petal cell
      identity that is independent of its role in repression of AG. These data suggest
      that ANT may function as a class A gene.

PMID- 10948256
TI  - Regions outside of the leucine-rich repeats of flax rust resistance proteins play
      a role in specificity determination.
AB  - Multiple alleles controlling different gene-for-gene flax rust resistance
      specificities occur at the L locus of flax. At least three distinct regions can
      be recognized in the predicted protein products: the Toll/interleukin-1 receptor
      homology (TIR) region, a nucleotide binding site (NBS) region, and a leucine-rich
      repeat (LRR) region. Replacement of the TIR-encoding region of the L6 allele with
      the corresponding regions of L2 or LH by recombination changed the specificity of
      the allele from L6 to L7. Replacement of the TIR and most of the NBS-encoding
      region of L10 with the equivalent region of L2 or L9 generated recombinant
      alleles having a novel specificity. However, replacement of the L10 TIR-encoding
      region with the TIR-encoding region of L2 gave rise to an allele with no
      detectable specificity. These data indicate that non-LRR regions can determine
      specificity differences between allelic gene products and that functional
      specificity involves interactions between coadapted polymorphic regions in the
      protein products of the alleles. Evidence for the action of diversifying
      selection on the TIR region is observed.

PMID- 10948257
TI  - The TITAN5 gene of Arabidopsis encodes a protein related to the ADP ribosylation
      factor family of GTP binding proteins.
AB  - The titan (ttn) mutants of Arabidopsis exhibit dramatic alterations in mitosis
      and cell cycle control during seed development. Endosperm development in these
      mutants is characterized by the formation of giant polyploid nuclei with enlarged
      nucleoli. Embryo development is accompanied by significant cell enlargement in
      some mutants (ttn1 and ttn5) but not others (ttn2 and ttn3). We describe here the
      molecular cloning of TTN5 using a T-DNA-tagged allele. A second allele with a
      similar phenotype contains a nonsense mutation in the same coding region. The
      predicted protein is related to ADP ribosylation factors (ARFs), members of the
      RAS family of small GTP binding proteins that regulate various cellular functions
      in eukaryotes. TTN5 is most closely related in sequence to the ARL2 class of ARF
      like proteins isolated from humans, rats, and mice. Although the cellular
      functions of ARL proteins remain unclear, the ttn5 phenotype is consistent with
      the known roles of ARFs in the regulation of intracellular vesicle transport.

PMID- 10948258
TI  - Identification of a calmodulin-regulated soybean Ca(2+)-ATPase (SCA1) that is
      located in the plasma membrane.
AB  - Ca(2)+-ATPases are key regulators of Ca(2+) ion efflux in all eukaryotes. Animal
      cells have two distinct families of Ca(2+) pumps, with calmodulin-stimulated
      pumps (type IIB pumps) found exclusively at the plasma membrane. In plants, no
      equivalent type IIB pump located at the plasma membrane has been identified at
      the molecular level, although related isoforms have been identified in non-plasma
      membrane locations. Here, we identify a plant cDNA, designated SCA1 (for soybean
      Ca(2+)-ATPase 1), that encodes Ca(2+)-ATPase and is located at the plasma
      membrane. The plasma membrane localization was determined by sucrose gradient and
      aqueous two-phase membrane fractionations and was confirmed by the localization
      of SCA1p tagged with a green fluorescent protein. The Ca(2+)-ATPase activity of
      the SCA1p was increased approximately sixfold by calmodulin (K(1/2) approximately
      10 nM). Two calmodulin binding sequences were identified in the N-terminal
      domain. An N-terminal truncation mutant that deletes sequence through the two
      calmodulin binding sites was able to complement a yeast mutant (K616) that was
      deficient in two endogenous Ca(2+) pumps. Our results indicate that SCA1p is
      structurally distinct from the plasma membrane-localized Ca(2+) pump in animal
      cells, belonging instead to a novel family of plant type IIB pumps found in
      multiple subcellular locations. In plant cells from soybean, expression of this
      plasma membrane pump was highly and rapidly induced by salt (NaCl) stress and a
      fungal elicitor but not by osmotic stress.

PMID- 10948259
TI  - Local and systemic changes in squash gene expression in response to silverleaf
      whitefly feeding.
AB  - Squash genes (SLW1 and SLW3) induced systemically after silverleaf whitefly
      feeding were identified. Differences in the local and systemic expression of SLW1
      and SLW3 after feeding by the closely related silverleaf and sweetpotato
      whiteflies were observed. Temporal and spatial studies showed that SLW1 and SLW3
      were induced when second, third, and fourth nymphal instars were feeding.
      Although only barely detected after wounding and bacterial infection, SLW1 and
      SLW3 RNAs were abundant during water-deficit stress. Treatments with
      wound/defense signal molecules showed that SLW1 RNAs accumulated in response to
      methyl jasmonate and ethylene, whereas SLW3 was not regulated by known
      wound/defense signals, suggesting utilization of a novel mechanism for defense
      signal transduction. SLW1 RNAs accumulated during floral and fruit development,
      whereas SLW3 RNAs were not detected during vegetative or reproductive
      development. The potential roles of SLW1, an M20b peptidase-like protein, and
      SLW3, a beta-glucosidase-like protein, in defense and the leaf-silvering disorder
      are discussed.

PMID- 10948260
TI  - Receptor-mediated increase in cytoplasmic free calcium required for activation of
      pathogen defense in parsley.
AB  - Transient influx of Ca(2+) constitutes an early element of signaling cascades
      triggering pathogen defense responses in plant cells. Treatment with the
      Phytophthora sojae-derived oligopeptide elicitor, Pep-13, of parsley cells stably
      expressing apoaequorin revealed a rapid increase in cytoplasmic free calcium
      ([Ca(2+)](cyt)), which peaked at approximately 1 microM and subsequently declined
      to sustained values of 300 nM. Activation of this biphasic [Ca(2+)](cyt)
      signature was achieved by elicitor concentrations sufficient to stimulate Ca(2+)
      influx across the plasma membrane, oxidative burst, and phytoalexin production.
      Sustained concentrations of [Ca(2+)](cyt) but not the rapidly induced
      [Ca(2+)](cyt) transient peak are required for activation of defense-associated
      responses. Modulation by pharmacological effectors of Ca(2+) influx across the
      plasma membrane or of Ca(2+) release from internal stores suggests that the
      elicitor-induced sustained increase of [Ca(2+)](cyt) predominantly results from
      the influx of extracellular Ca(2+). Identical structural features of Pep-13 were
      found to be essential for receptor binding, increases in [Ca(2+)](cyt), and
      activation of defense-associated responses. Thus, a receptor-mediated increase in
      [Ca(2+)](cyt) is causally involved in signaling the activation of pathogen
      defense in parsley.

PMID- 10948262
TI  - Expansin message regulation in parasitic angiosperms: marking time in
      development.
AB  - Parasitic strategies are widely distributed across the angiosperms and are
      estimated to have evolved at least eight different times. Within the obligate
      hemiparasitic and holoparasitic members, elaborate strategies for host selection
      have emerged. Here, we demonstrate that in the parasitic Scrophulariceae Striga
      asiatica, for which signal-mediated host detection is critical, expansin mRNA
      provides a reliable and accurate downstream molecular marker for the transition
      to the parasitic mode. Three different expansin genes, saExp1, saExp2, and
      saExp3, are regulated by xenognostic quinones. saExp3 appears to function as a
      seedling expansin, and its mRNA is depleted within minutes after induction of the
      host attachment organ. saExp1 and saExp2 share less homology with the known
      expansins, and their transcripts accumulate linearly over a critical induction
      period. The regulation of these genes suggests that the resources for
      developmental commitment must accumulate to a defined threshold before commitment
      to organogenesis is terminal. When the induction signal is removed prematurely,
      the accumulated message decays with a time constant that correlates with the time
      required for additional signal exposures to reinduce parasitic development. These
      results suggest that sophisticated controls exist for the accumulation of the
      necessary components for terminal commitment to the parasitic mode. Furthermore,
      building on the redox dependence of the inducing signal, they suggest a model
      akin to a "molecular capacitor" for clocking organogenesis in S. asiatica.

PMID- 10948261
TI  - The Chlamydomonas reinhardtii Nar1 gene encodes a chloroplast membrane protein
      involved in nitrite transport.
AB  - A key step for nitrate assimilation in photosynthetic eukaryotes occurs within
      chloroplasts, where nitrite is reduced to ammonium, which is incorporated into
      carbon skeletons. The Nar1 gene from Chlamydomonas reinhardtii is clustered with
      five other genes for nitrate assimilation, all of them regulated by nitrate.
      Sequence analysis of genomic DNA and cDNA of Nar1 and comparative studies of
      strains having or lacking Nar1 have been performed. The deduced amino acid
      sequence indicates that Nar1 encodes a chloroplast membrane protein with
      substantial identity to putative formate and nitrite transporters in bacteria.
      Use of antibodies against NAR1 has corroborated its location in the plastidic
      membrane. Characterization of strains having or lacking this gene suggests that
      NAR1 is involved in nitrite transport in plastids, which is critical for cell
      survival under limiting nitrate conditions, and controls the amount of nitrate
      incorporated by the cells under limiting CO(2) conditions.

PMID- 10948263
TI  - Wound-induced expression and activation of WIG, a novel glycogen synthase kinase
      3.
AB  - Glycogen synthase kinase 3 (GSK-3) is involved in the regulation of several
      physiological processes, including glycogen metabolism, protein synthesis,
      transcription factor activity, and developmental control. Although GSK-3-like
      genes have been isolated from plants, no function for any of these kinases has
      been defined. We report here that the alfalfa wound-induced gene (WIG, for wound
      induced GSK-3), lencoding a functional plant GSK-3-like kinase, is activated when
      the alfalfa leaves are wounded. Although WIG transcripts are hardly detectable in
      mature leaves, WIG mRNA accumulates rapidly after wounding. Using a peptide
      antibody that specifically recognizes p53(WIG), we show that p53(WIG) kinase is
      activated immediately after wounding. Wound-induced activation of p53(WIG) kinase
      is a post-translational process, because the concentrations of p53(WIG) protein
      do not change in intact and wounded leaves, and inhibition of transcription or
      translation does not block activation by wounding. However, inactivation of
      p53(WIG) kinase, which usually occurs within 60 min after wounding, is dependent
      on transcription and translation of one or more protein factors. These data
      suggest that the WIG kinase is involved in wound signaling in plants.

PMID- 10948264
TI  - PBF-2 is a novel single-stranded DNA binding factor implicated in PR-10a gene
      activation in potato.
AB  - Elicitor-induced activation of the potato pathogenesis-related gene PR-10a
      requires a 30-bp promoter sequence termed the ERE (elicitor response element)
      that is bound by the nuclear factor PBF-2 (PR-10a binding factor 2). In this
      study, PBF-2 has been purified to near homogeneity from elicited tubers through a
      combination of anion-exchange and DNA affinity chromatography. Evidence
      demonstrates that inactive PBF-2 is stored in the nuclei of fresh tubers and
      becomes available for binding to the ERE upon elicitation. A protein with an
      apparent molecular mass of 24 kD (p24) is a DNA binding component of PBF-2. A
      cDNA encoding p24 has been cloned and encodes a novel protein with a potential
      transcriptional activation domain that could also act as a single-stranded DNA
      binding domain. Both PBF-2 and the cDNA-encoded protein bind with high affinity
      to the single-stranded form of the ERE in a sequence-specific manner. The
      inverted repeat sequence of the ERE, TGACAnnnnTGTCA, is critical for binding of
      this factor in vitro and for PR-10a expression in vivo, supporting the role of
      PBF-2 as a transcriptional regulator.

PMID- 10948266
TI  - Dynamics and phylogenetic implications of MtDNA control region sequences in New
      World Jays (Aves: Corvidae).
AB  - To study the evolution of mtDNA and the intergeneric relationships of New World
      Jays (Aves: Corvidae), we sequenced the entire mitochondrial DNA control region
      (CR) from 21 species representing all genera of New World jays, an Old World jay,
      crows, and a magpie. Using maximum likelihood methods, we found that both the
      transition/transversion ratio (kappa) and among site rate variation (alpha) were
      higher in flanking domains I and II than in the conserved central domain and that
      the frequency of indels was highest in domain II. Estimates of kappa and alpha
      were much more influenced by the density of taxon sampling than by alternative
      optimal tree topologies. We implemented a successive approximation method
      incorporating these parameters into phylogenetic analysis. In addition we
      compared our study in detail to a previous study using cytochrome b and
      morphology to examine the effect of taxon sampling, evolutionary rates of genes,
      and combined data on tree resolution. We found that the particular weighting
      scheme used had no effect on tree topology and little effect on tree robustness.
      Taxon sampling had a significant effect on tree robustness but little effect on
      the topology of the best tree. The CR data set differed nonsignificantly from the
      tree derived from the cytochrome b/morphological data set primarily in the
      placement of the genus Gymnorhinus, which is near the base of the CR tree.
      However, contrary to conventional taxonomy, the CR data set suggested that blue
      and black jays (Cyanocorax sensu lato) might be paraphyletic and that the brown
      jay Psilorhinus (=Cyanocorax) morio is the sister group to magpie jays
      (Calocitta), a phylogenetic hypothesis that is likely as parsimonious with regard
      to nonmolecular characters as monophyly of Cyanocorax. The CR tree also suggests
      that the common ancestor of NWJs was likely a cooperative breeder. Consistent
      with recent systematic theory, our data suggest that DNA sequences with high
      substitution rates such as the CR may nonetheless be useful in reconstructing
      relatively deep phylogenetic nodes in avian groups.

PMID- 10948265
TI  - Genomic analysis of a nutrient response in Arabidopsis reveals diverse expression
      patterns and novel metabolic and potential regulatory genes induced by nitrate.
AB  - Microarray and RNA gel blot analyses were performed to identify Arabidopsis genes
      that responded to nitrate at both low (250 microM) and high (5 to 10 mM) nitrate
      concentrations. Genes involved directly or indirectly with nitrite reduction were
      the most highly induced by nitrate. Most of the known nitrate-regulated genes
      (including those encoding nitrate reductase, the nitrate transporter NRT1, and
      glutamate synthase) appeared in the 40 most strongly nitrate-induced genes/clones
      on at least one of the microarrays of the 5524 genes/clones investigated. Novel
      nitrate-induced genes were also found, including those encoding (1) possible
      regulatory proteins, including an MYB transcription factor, a calcium antiporter,
      and putative protein kinases; (2) metabolic enzymes, including transaldolase and
      transketolase of the nonoxidative pentose pathway, malate dehydrogenase,
      asparagine synthetase, and histidine decarboxylase; and (3) proteins with unknown
      functions, including nonsymbiotic hemoglobin, a senescence-associated protein,
      and two methyltransferases. The primary pattern of induction observed for many of
      these genes was a transient increase in mRNA at low nitrate concentrations and a
      sustained increase when treated with high nitrate concentrations. Other patterns
      of induction observed included transient inductions after both low and high
      nitrate treatments and sustained or increasing amounts of mRNA after either
      treatment. Two genes, AMT1;1 encoding an ammonium transporter and ANR1 encoding a
      MADS-box factor, were repressed by nitrate. These findings indicate that nitrate
      induces not just one but many diverse responses at the mRNA level in Arabidopsis.

PMID- 10948267
TI  - Six opsins from the butterfly Papilio glaucus: molecular phylogenetic evidence
      for paralogous origins of red-sensitive visual pigments in insects.
AB  - It has been hypothesized that the UV-, blue-, and green-sensitive visual pigments
      of insects were present in the common ancestor of crustaceans and insects,
      whereas red-sensitive visual pigments evolved later as a result of convergent
      evolution. This hypothesis is examined with respect to the placement of six
      opsins from the swallowtail butterfly Papilio glaucus (PglRh1-6) in relationship
      to 46 other insect, crustacean, and chelicerate opsin sequences. All basal
      relationships established with maximum parsimony analysis except two are present
      in the distance and maximum likelihood analyses. In all analyses, the six P.
      glaucus opsins fall into three well-supported clades, comprised, respectively, of
      ultraviolet (UV), blue, and long-wavelength (LW) pigments, which appear to
      predate the radiation of the insects. Lepidopteran green- and red-sensitive
      visual pigments form a monophyletic clade, which lends support to the hypothesis
      from comparative physiological studies that red-sensitive visual pigments in
      insects have paralogous origins. Polymorphic amino acid sites (180, 197, 277,
      285, 308), which are essential for generating the spectral diversity among the
      vertebrate red- and green-sensitive pigments are notably invariant in the Papilio
      red- and green-sensitive pigments. Other major tuning sites must be sought to
      explain the spectral diversification among these and other insect visual
      pigments.

PMID- 10948268
TI  - Phylogenetic position of the subgenus Lordiphosa of the genus Drosophila
      (Diptera: Drosophilidae) inferred from alcohol dehydrogenase (Adh) gene
      sequences.
AB  - We analyzed the phylogenetic relationship between the species of Lordiphosa and
      other Drosophilidae using alcohol dehydrogenase (Adh) gene sequences. The
      phylogenetic trees consistently show that the four species Drosophila kurokawai,
      D. collinella, D. stackelbergi, and D. clarofinis, which include three species
      groups of Lordiphosa, form a monophyletic clade. This clade is placed as a sister
      group to the willistoni and saltans groups of Sophophora. On the other hand,
      three species of Lordiphosa, D. tenuicauda, D. pseudotenuicauda, and D.
      acutissima, all of which belong to the tenuicauda group, are not shown to be
      related to the major Lordiphosa lineage. In the phylogenetic trees, these species
      are included into the clade comprised of Drosophila and Hirtodrosophila, although
      it remains uncertain whether the tenuicauda group is a monophyletic group or not.
      These results indicate that Lordiphosa is polyphyletic and that most of the
      members of the subgenus have a close relationship to the neotropical groups of
      Sophophora. The above conclusion is compatible with the hypothesis of Okada
      (Mushi [1963] 37:79-100) and Lastovka and Maca (Acta Ent Bohemoslov [1978] 75:404
      420) that Lordiphosa is most closely related to Sophophora; in contrast, our
      results contradict the hypothesis of Grimaldi (Bull Am Mus Nat Hist [1990] 197:1
      139) that Lordiphosa is a sister group to the genus Scaptomyza.

PMID- 10948269
TI  - Evolution of simple sequence in proteins.
AB  - The proteins of Saccharomyces cerevisiae contain a high proportion of low
      complexity, simple sequences. These are protein segments composed almost
      exclusively or largely of a single repetitive amino acid polymer and are the most
      commonly shared feature between proteins. We have examined a survey of other
      species to determine how widespread this phenomenon might be. This was done by
      comparing how frequently segments from one protein are present in other proteins.
      Any recently evolutionarily related proteins were excluded. It was found that the
      most commonly shared features of eukaryotic proteins were repetitive but that
      prokaryotes did not contain such shared, extensively redundant repeats. The
      proportion of eukaryotic proteins that contain a significantly repetitive
      fraction changes dramatically from species to species. In addition the individual
      amino acids present in these repeats change between species. This suggests that
      the primary sequence of the repeats may not be important for their function.
      Further tests of the yeast repeats confirmed that these repeats evolve more
      quickly than the remainder of the protein sequence within which they are
      embedded. These results show that these rapid evolving, simple sequence repeats
      are in fact the most commonly shared pattern between all of the genomic proteins
      of eukaryotes.

PMID- 10948270
TI  - Molecular evolution of calmodulin and calmodulin-like genes in the
      cephalochordate Branchiostoma.
AB  - Calmodulin is a calcium-binding EF-hand protein that is an activator of many
      enzymes as well as ion pumps and channels. Due to its multiple targets and its
      central role in the cell, understanding the evolutionary history of calmodulin
      genes should provide insights into the origin of genetic complexity in
      eukaryotes. We have previously isolated and characterized a calmodulin gene from
      the early-diverging chordate Branchiostoma lanceolatum (CaM1). In this paper, we
      report the existence of a second calmodulin gene (CaM2) as well as two CaM-like
      genomic fragments (CaML-2, CaML-3) in B. lanceolatum and a CaM2 and three CaM
      like genes (CaML-1, CaML-2, CaML-3) in B. floridae. The CaM-like genes were
      isolated using low-stringency PCR. Surprisingly, the nucleotide sequences of the
      B. lanceolatum CaM1 and CaM2 cDNAs differ by 19.3%. Moreover, the CaM2 protein
      differs at two positions from the amino acid sequence of CaM1; the latter is
      identical to calmodulins in Drosophila melanogaster, the mollusc Aplysia
      californica, and the tunicate Halocynthia roretzi. The two B. lanceolatum CaM
      like genes are more closely related to the CaM2 than to the CaM1 gene. This
      relationship is supported by the phylogenetic analyses and the identical
      exon/intron organization of these three genes, a relationship unique among animal
      CaM sequences. These data demonstrate the existence of a CaM multigene family in
      the cephalochordate Branchiostoma, which may have evolved independently from the
      multigene family in vertebrates.

PMID- 10948271
TI  - Reconstructing the diversification of alpha-esterases: comparing the gene
      clusters of Drosophila buzzatii and D. melanogaster.
AB  - A cluster composed of 10 active alpha-esterase genes and a pseudogene is
      distributed over 60 kb in the Drosophila melanogaster genome. This paper
      describes the corresponding cluster in Drosophila buzzatii, whose lineage
      diverged from that of D. melanogaster when the subgenera Drosophila and
      Sophophora diverged about 50 Mya. With three exceptions we find that the
      composition of the cluster is conserved in the two lineages. The location of
      alpha E1 in D. melanogaster differs from that of its nearest relative in D.
      buzzatii, and alpha E4 has duplicated independently in the two lineages. The
      nature of these differences indicates that a mechanism exists whereby copies of
      genes can be placed in opposite orientation and nonadjacent positions within a
      gene cluster, although this does not seem to be a feature of earlier events in
      the cluster's evolution. The rates of amino acid change are not significantly
      different between orthologs, but the rates differ sevenfold among paralogs,
      indicating that very different selective forces are acting on the genes of the
      cluster. Mapping of sequence differences onto a model of the tertiary structure
      of the enzymes indicates that motifs contributing to substrate binding and
      catalysis have changed radically in the alphaE4s and suggest that this subgroup
      of alpha-esterases may be evolving into a substantially different functional
      niche.

PMID- 10948272
TI  - Interspecific comparison in the frequency of concerted evolution at the
      polyubiquitin gene locus.
AB  - The polyubiquitin gene, encoding tandemly repeated multiple ubiquitins,
      constitutes a uniquitin gene subfamily. It has been demonstrated that
      polyubiquitin genes are subject to concerted evolution; namely, the individual
      ubiquitin coding units contained within a polyubiquitin gene are more similar to
      one another than they are to the ubiquitin coding units in the orthologous gene
      from other species. However there has been no comprehensive study on the
      concerted evolution of polyubiquitin genes in a wide range of species, because
      the relationships (orthologous or paralogous) among multiple polyubiquitin genes
      from different species have not been extensively analyzed yet. In this report, we
      present the results of analyzing the nucleotide sequence of polyubiquitin genes
      of mammals, available in the DDBJ/EMBL/GenBank nucleotide sequence databases, in
      which we found that there are two groups of polyubiquitin genes in an orthologous
      relationship. Based on this result, we analyzed the concerted evolution of the
      polyubiquitin gene in various species and compared the frequency of concerted
      evolutionary events interspecifically by taking into consideration that the rate
      of synonymous substitution at the polyubiquitin gene locus may vary depending on
      species. We found that the concerted evolutionary events in polyubiquitin genes
      have been more frequent in rats and Chinese hamsters than those in humans, cows,
      and sheep. The guinea pig polyubiquitin gene was an intermediate example. The
      frequency of concerted evolution in the mouse gene was unexpectedly low compared
      to that of other rodent genes.

PMID- 10948273
TI  - Evolution of microsatellite alleles in four species of mice (genus Apodemus).
AB  - Microsatellite length variation was investigated at a highly variable
      microsatellite locus in four species of Apodemus. Information obtained from
      microsatellite allele sequences was contrasted with allele sizes, which included
      18 electromorphs. Additional analysis of a 400-bp unique sequence in the flanking
      region identified 26 different haplotype sequences or "true" alleles in the
      sample. Three molecular mechanisms, namely, (1) addition/deletion of repeats, (2)
      substitutions and indels in the flanking region, and (3) mutations interrupting
      the repeat, contributed to the generation of allelic variation. Size homoplasy
      can be inferred for alleles within populations, from different populations of the
      same species, and from different species. We propose that microsatellite flanking
      sequences may be informative markers for investigating mutation processes in
      microsatellite repeats as well as phylogenetic relationships among alleles,
      populations, and species.

PMID- 10948274
TI  - Determining the relative rates of change for prokaryotic and eukaryotic proteins
      with anciently duplicated paralogs.
AB  - The relative rates of change for eight sets of ubiquitous proteins were
      determined by a test in which anciently duplicated paralogs are used to root the
      universal tree and distances are calculated between each taxonomic group and the
      last common ancestor. The sets included ATPase subunits, elongation factors,
      signal recognition particle and its receptor, three sets of tRNA synthetases,
      transcarbamoylases, and an internal duplication in carbamoyl phosphate synthase.
      In each case phylogenetic trees were constructed and the distances determined for
      all pairs. Taken over the period of time since their last common ancestor,
      average evolutionary rates are remarkably similar for Bacteria and Eukarya, but
      Archaea exhibit a significantly slower average rate.

PMID- 10948275
TI  - Ribozyme relationships: the hammerhead, hepatitis delta, and hairpin ribozymes
      have a common origin.

PMID- 10948276
TI  - Relative potencies of individual polychlorinated naphthalenes to induce dioxin
      like responses in fish and mammalian in vitro bioassays.
AB  - A growing body of evidence suggests that polychlorinated naphthalenes (PCNs) may
      be fairly widespread environmental contaminants. This may be cause for concern
      because exposure to PCNs has been linked to dioxin-like biological responses in a
      wide variety of species. This study used three in vitro bioassays to characterize
      the dioxin-like potency of 18 individual PCN congeners and 1 PCN metabolite. The
      PLHC-1 fish hepatoma cell bioassay was relatively insensitive to PCNs. At the
      concentrations tested, only 1, 4 di-CN and 2,4-dichloro-1-napthol caused
      significant induction of ethoxyresorufin O-deethylase (EROD) activity in the PLHC
      1 assay. In vitro EROD and luciferase assays using recombinant H4IIE rat hepatoma
      cells were more responsive to PCNs. Structure-activity relationships were
      observed both in terms of the degree of chlorination and the positions of
      chlorine substitutions. Hexa-chlorinated naphthalenes (CNs), exhibiting relative
      potencies (REPs) around 10(-3) (relative to TCDD), were the most potent congeners
      tested. Penta-CNs were also rather potent, yielding REPs between 10(-3) and 10(
      7). Tetra-, tri-, di-, and mono-CNs were less active. REPs for the active
      congeners were similar to those for some PCBs. The relative potency estimates
      reported here contribute to an emerging body of information that will aid
      determination of the relative contribution of PCNs to the total dioxin-like
      activity associated with environmental samples.

PMID- 10948277
TI  - Metalaxyl and simazine toxicity to and uptake by Typha latifolia.
AB  - This research focused on the potential use of common cattails (Typha latifolia)
      for removing metalaxyl and simazine residues from contaminated water.
      Specifically, it established toxicity thresholds to the herbicide simazine and
      characterized the uptake and distribution of simazine and metalaxyl by the
      plants. Simazine tolerance levels were determined by exposing plants to a series
      of six concentrations (0-3.0 mg L(-1)) in aqueous nutrient media for 7 days.
      Metalaxyl toxicity was not evaluated because other studies indicated it was
      relatively nontoxic to plants. Toxicity endpoints measured included fresh mass
      production after 7 days of exposure and 7 days postexposure. Pesticide uptake and
      distribution were determined by growing plants in nutrient media amended with
      (14)C-ring-labeled metalaxyl (0.909 mg L(-1)) or simazine (0.242 mg L(-1)) for 1,
      3, 5, or 7 days. Plants were dissected, and tissues were combusted and analyzed
      by liquid scintillation spectroscopy. Cattail fresh mass production was reduced
      84 and 117% at 1.0 and 3.0 mg L(-1) simazine, respectively, after 7 days of
      exposure. Metalaxyl and simazine activity in solution was reduced 34 and 65%,
      respectively, after 7 days. By day 7, activity from both pesticides was detected
      predominantly in the leaves. Uptake of each pesticide was correlated with water
      uptake throughout the 7 days. These results suggest that the common cattail may
      be a good candidate for incorporation into a phytoremediation scheme for
      metalaxyl and simazine.

PMID- 10948278
TI  - Modeling the toxicity of chemicals to Tetrahymena pyriformis using molecular
      fragment descriptors and probabilistic neural networks.
AB  - The results of an investigation into the use of a probabilistic neural network
      (PNN)-based methodology to model the 48-h ICG50 (inhibitory concentration for
      population growth) sublethal toxicity of 825 chemicals to the ciliate Tetrahymena
      pyriformis are presented. The information fed into the neural networks is solely
      based on simple molecular descriptors as can be derived from the chemical
      structure. In contrast to most other toxicological models, the octanol/water
      partition coefficient is not used as an input parameter, and no rules of thumb or
      other substance selection criteria are employed. The cross-validation and
      external validation experiments confirmed excellent recognitive and predictive
      capabilities of the resulting models and recommend their future use in evaluating
      the potential of most organic molecules to be toxic to Tetrahymena.

PMID- 10948279
TI  - A comparative study of Chironomus riparius Meigen and Chironomus tentans
      Fabricius (diptera:chironomidae) in aquatic toxicity tests.
AB  - Chironomus riparius Meigen and Chironomus tentans Fabricius were examined under
      controlled conditions and exposed to the reference toxicants cadmium and lindane
      (gamma-hexachlorocyclohexane) to identify any differences that could have
      implications for their use in aquatic toxicity testing. Preliminary studies
      showed that both species could be cultured in the laboratory using similar
      methodology, resulting in the typical bimodal emergence of adult males prior to
      females. However, adults of C. riparius emerged earlier and in greater numbers
      than C. tentans. Comparative measurements of head capsule width and body length
      for the four larval instars revealed similar dimensions for each species up to
      and including the third instar. Fourth-instar larvae of C. tentans were
      considerably larger than those of C. riparius. Median lethal concentrations
      (LC50) determined over a 10-day exposure period suggested no difference in
      species response to cadmium; however, with increasing exposure time, C. tentans
      was significantly more sensitive to lindane. The investigations showed that the
      pattern of response was similar for the two species, and that both C. riparius
      and C. tentans are suitable test organisms for acute exposure assays.

PMID- 10948280
TI  - Effects of benzo(a)pyrene and size of organic matter particles on bioaccumulation
      and growth of Asellus aquaticus.
AB  - The effects of sediment-bound toxicants to aquatic invertebrates may vary due to
      differences in bioavailability, food quality, or food structure. The equilibrium
      partitioning theory (EPT) assumes that organic matter content of sediments and
      not structure of organic matter is relevant for biological effects of polycyclic
      aromatic hydrocarbons. To test this hypothesis effects of benzo(a)pyrene (B(a)P)
      and size of sediment organic matter particles on the bioaccumulation and growth
      of the waterlouse Asellus aquaticus were studied in laboratory microcosms.
      Sediments and A. aquaticus were both sampled in an unpolluted, spring-fed pond.
      The sampled sediment was divided into two portions. From one portion the size of
      the organic matter particles was mechanically reduced. One set of each sediment
      fraction (fine and coarse) was spiked with B(a)P and incubated for 3 weeks
      resulting in a concentration of 70 mg B(a)P per kg sediment. Bioassays of 32 days
      were performed in a 2 x 2 factorial design with four replicas of each treatment.
      The results showed that the growth of A. aquaticus was mainly influenced by the
      size of organic matter particles. Growth was significantly less (27%) on finer
      sediments than on coarser sediments. The increase in length was 9-14% lower in
      the spiked sediments, but this difference was not significant. The reduced growth
      of A. aquaticus on finer sediments may be due to a change in the availability
      and/or quality of food together with a change in feeding behavior. The coarse and
      fine spiked sediment types did not differ significantly with respect to the
      sediment water partition coefficient, the organic carbon water partition
      coefficient, and the bioconcentration factor. In contrast, the biota to sediment
      accumulation factors were significantly 15% higher in the cosms with coarse
      sediments than in cosms with fine sediments. However, this difference is too
      small to conflict with EPT.

PMID- 10948281
TI  - Ecotoxicity of contaminated suspended solids for filter feeders (Daphnia magna).
AB  - It is generally assumed that the dissolved fraction of a toxic substance in
      surface water is mainly responsible for toxicity to aquatic organisms. However,
      toxic compounds are often adsorbed or chemically bound to suspended particles in
      the water column, depending upon the physico-chemical conditions. In the present
      study potential adverse effects to filter feeding organisms by metal contaminated
      particles were investigated. In our hypotheses the adsorbed metals might desorb
      in the gastrointestinal tract-due to different physico-chemical conditions-and
      exert toxic effects. Clay and sand particles, algae and organic material (peat)
      were artificially contaminated with cadmium and zinc. The contaminated materials
      were resuspended in standard conditions and toxicity was measured for the water
      flea Daphnia magna (mortality at 48 hours). As a reference, supernatant solutions
      were used containing the same concentration of dissolved metal as the
      suspensions. It was also established that the test concentrations of solid
      material (250 and 500 mg/l uncontaminated particles) did not cause any mortality
      within 48 hours. Daphnids are filter feeders: they filtrate large amounts of
      surrounding water, redrawing particles as a food source. Results strongly
      indicate that contaminated particles threaten the health of these particle
      feeding organisms. Compared to the reference severe acute toxic effects were seen
      and cadmium accumulation was increased when contaminated solid material was
      present. Results were essentially the same for the different materials used in
      the experiments, except for sand contaminated with cadmium. This shows that
      mineral as well as organic materials can contribute to the particle bound
      toxicity. Different results were obtained when a static set up was used instead
      of a flow through set up, illustrating that the route of administration is
      important to make particles available and thus to evaluate their toxicity.
      Contaminated particles clearly have toxic potency, not only because they are a
      continuous source of dissolved xenobiotics, but also because the particle bound
      fraction can become available within the body of particle feeding organisms. This
      could lead to unexpected high tissue concentrations. More insight is needed to
      predict the bioavailability of adsorbed pollutants. Results of this study already
      indicate that suspended solids should be considered as a separate compartment in
      risk evaluation of chemicals, effluents or natural surface waters.

PMID- 10948282
TI  - Evaluating mosquito control pesticides for effect on target and nontarget
      organisms.
AB  - Recent requirements for biomonitoring of urban stormwater runoff have raised the
      issue of toxic contributions from mosquito control products. A comparison of
      seven pesticides for their toxicity to target and nontarget organisms was
      conducted in field and laboratory trials to determine relative impacts in and
      around Craighead County, Arkansas. Twenty-four and forty-eight-hour acute
      toxicity tests using Ceriodaphnia dubia, Daphnia magna, Daphnia pulex, and
      Pimephales promelas were employed with U.S. Environmental Protection Agency (U.S.
      EPA) suggested procedures as standard test organisms. Additional tests with
      resident mosquito fish, Gambusia affinis, and mosquito larvae, Anopheles
      quadrimaculatus, included ditch-receiving waters to compare the somewhat sterile
      laboratory exposures to actual field conditions. Exposure to as much as 31.4
      microg/L of the pesticides Dursban(R), malathion, Permanone(R), Abate(R),
      Scourge(R), B.t.i, and Biomist(R) were required for effective control of An.
      quadrimaculatus, whereas as little as 2.7 microg/L resulted in substantial
      mortality of some nontarget organisms. These data suggest that prevailing
      application rates for effective mosquito control not only affect nontarget
      organisms but may also confound stormwater and nonpoint toxicity evaluations that
      utilize sensitive indicator species.

PMID- 10948283
TI  - The toxicity of a neem insecticide to populations of culicidae and other aquatic
      invertebrates as assessed in in situ microcosms.
AB  - Microcosm trials were conducted with the botanical insecticide Margosan-O(R) to
      assess the potential hazards of the product to aquatic organisms. Laboratory
      chronic bioassays with water from the treated microcosms were conducted to
      provide an estimate of the residual effect of Margosan-O. Results from chronic
      tests showed Margosan-O toxicity to be greater in the laboratory exposures than
      in situ with Culicidae larvae exposed to the same concentrations. Residue
      analyses of the active ingredient, azadirachtin, determined that it had a half
      life of 36 to 48 h in water exposed to natural sunlight. Two applications of
      Margosan-O at the recommended application rate for pests did not harm aquatic
      invertebrates that are categorized as planktonic and filter feeding (Culex sp.
      and Daphnia sp.). However, the benthic invertebrate (Chironomus riparius) was
      affected by multiple applications of neem. These results show that the use of
      Margosan-O and possibly other neem extracts in or near aquatic environments could
      lead to disturbances in benthic populations and may cause decreases in numbers of
      organisms that are important in food web and nutrient cycling processes.

PMID- 10948284
TI  - Comparison of embryonic development and metal contamination in several
      populations of the sea urchin Sphaerechinus granularis (Lamarck) exposed to
      anthropogenic pollution.
AB  - Over the past years the functional deficiencies observed in the sea urchin
      Sphaerechinus granularis from the Bay of Brest (France) have led us to select
      several populations within this species to assess water quality in the Bay of
      Brest. The present study reports on the comparison of the quality of embryonic
      development and of the level of metal contamination in sea urchin gonads and gut
      wall in four populations. Three of them lived in the Bay of Brest, and the last
      one was considered a reference, being settled in the Glenan Archipelago in
      southern Brittany (France). The sea urchin population living at the mouth of the
      River Aulne, at the Armorique Point, seemed to be the most affected, for it
      displayed the highest rate of blockage and the longest delay in embryonic
      development along with the highest concentrations in heavy metals, i.e., Fe, Cu,
      Pb, Cd, and Hg, in the gut wall and in the gonads. A comparison with previous
      data highlighted a degradation of health conditions in the population living at
      Marloux in the vicinity of Brest harbor. The comparison of the metal levels
      detected in individuals from these two populations with the data reported in the
      literature allowed us to conclude for a local contamination of the bay waters by
      Fe and Hg. In addition, this study also revealed that Zn and Cd concentrations
      were sometimes higher than the maximum values reported in the literature and
      evidenced an increase of contamination by Cu and Pb over the period of study; it
      should be noted, however, that these values were not excess levels. Our
      investigations also suggest that Zn, Cd, Pb, and Cu levels should be monitored in
      the future.

PMID- 10948285
TI  - Comparative toxicity of dissolved metals to early larval stages of Palaemon
      serratus, Maja squinado, and Homarus gammarus (Crustacea:Decapoda).
AB  - The acute lethal toxicities of mercury, copper, and cadmium to the first larval
      stage of the prawn (Palaemon serratus), spider crab (Maja squinado), and lobster
      (Homarus gammarus) were tested. Chromium was also tested with the prawn.
      Mortality was recorded after 48 h (for lobster) or 72 h (for other species)
      incubation at 18 degrees C, and the median lethal concentrations (LC(50) +/- 95%
      confidence intervals) per individual and per mass unit were calculated. The
      LC(50) values were, 74 microg Hg/L, 3,304 microg Cu/L, 1,686 microg Cd/L, 12,486
      microg Cr/L for prawn; 72 microg Hg/L, 50 microg Cu/L, 158 microg Cd/L for spider
      crab; and 48 microg Hg/L, 46 microg Cu/L, 34 microg Cd/L for lobster. Therefore,
      larvae of spider crab and lobster were markedly more sensitive than prawn to
      heavy metals and thus more suitable to use in seawater quality bioassays. Of
      these two species, spider crab is recommended due to its abundance, easier
      maintenance, and higher fecundity. The mercury LC(50) values for different larval
      stages of P. serratus (zoea I, II, V, and VI) were obtained, and no ontogenetic
      change in sensitivity to the metal could be detected.

PMID- 10948286
TI  - Toxicokinetics of 2,4,5-trichlorophenol and benzo(a)pyrene in the clam Pisidium
      amnicum: effects of seasonal temperatures and trematode parasites.
AB  - Several biotic and abiotic stress factors may affect aquatic organisms
      simultaneously. However, not much is known about the effects of, e.g., low
      temperatures and parasite infections on the toxicokinetics of organic hydrophobic
      chemicals. Here we studied the accumulation and depuration of [(14)C]2,4,5
      trichlorophenol (TCP) and [(3)H]benzo(a)pyrene (BaP) in the sediment-dwelling
      freshwater clam Pisidium amnicum. Experiments were made in October (+15 degrees
      C), April (+4 degrees C), and July (+15 degrees C) both with uninfected clams and
      clams infected with Bunodera luciopercae (Trematoda). The accumulation rate for
      both chemicals was slower at 4 degrees C than at 15 degrees C. The depuration of
      TCP was biphasic, and the slowest depuration occurred at 4 degrees C. For BaP,
      the depuration was very slow and monophasic at all temperatures. The highest BCFs
      for both chemicals were found in July at 15 degrees C. Surprisingly, the BCFs for
      TCP were higher in April at 4 degrees C than in October at 15 degrees C. For BaP,
      no steady-state was reached in April. Differences in chemical toxicokinetics
      between the infected and uninfected clams were only minor. However, for both
      chemicals a trend of slightly lower BCFs in the infected clams was found. In
      conclusion, low temperatures modify the toxicokinetics of organic chemicals in P.
      amnicum and the effects depend on hydrophobicity of the chemical. The effects of
      parasites on toxicokinetics seem to be small.

PMID- 10948287
TI  - Instrumental and bioanalytical measures of persistent organochlorines in blue
      mussel (Mytilus edulis) from Korean coastal waters.
AB  - Blue mussels (Mytilus edulis) collected from 34 locations along the south and
      east coast of Korea were analyzed for polychlorinated biphenyls (PCBs) and
      organochlorine (OC) pesticides. Maximum concentrations of PCBs and total OC
      pesticides were 98.5 and 20.5 ng/g, wet weight, respectively. Extracts were
      fractionated by Florisil chromatography and each fraction was screened for dioxin
      like activity in vitro, using recombinant rat hepatoma cells (H4IIE-luc).
      Fraction 2 (F-2), which contained hexachlorocyclohexanes, chlordanes, p,p'-DDD,
      and p,p'-DDT, generally elicited significant dioxin-like activity compared to
      control, whereas Fraction 1 (F-1), which contained PCBs, p,p'-DDE, and
      hexachlorobenzene, did not. The greatest magnitude of dioxin-like response
      observed was 44% of the maximum response elicited by a 2,000 pM 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) standard. The relatively low magnitudes of
      dioxin-like response observed for F-1 samples were consistent with the relatively
      low PCB concentrations. At concentrations equal to the maximum observed in the
      mussel samples, neither individual OC pesticides nor a mixture of OC pesticides
      yielded a significant dioxin-like response in the H4IIE-luc assay. Thus, the
      concentrations of OC pesticides in F-2 did not appear to have accounted for the
      dioxin-like activity observed. This suggests the presence of unidentified and/or
      unknown, acid-stable, dioxin-like compounds in F-2. This study suggests that in
      vitro bioassays are useful in assessing the contamination of mussels collected
      from coastal marine locations.

PMID- 10948289
TI  - Growth-related changes in heavy metal accumulation in green turtle (Chelonia
      mydas) from Yaeyama Islands, Okinawa, Japan.
AB  - Concentrations of nine heavy metals (Fe, Mn, Zn, Cu, Pb, Ni, Cd, Co, and Hg) were
      determined in liver, kidney, and muscle of 50 green turtles (Chelonia mydas)
      collected from Yaeyama Islands, Okinawa, Japan, to elucidate growth-related
      changes in heavy metal accumulation during different growth stage. Considerably
      high Cu concentrations were found in the liver of smaller turtles. Mean hepatic
      concentration of Cu was 50.2 microg/g wet weight which varied widely (4.27-113
      microg/g wet weight). Cadmium concentrations decreased with increasing the
      carapace length. The juvenile green turtles in the pelagic ocean are likely feed
      on zooplankton, while adult coastal inhabiting green turtles mainly feed on sea
      grasses and seaweeds. Concentrations of Cd in sea plants are lower than those in
      zooplankton. The specific accumulation of Cd found in the green turtle seems to
      be attributable to their feeding habit, which is a shift from carnivore to
      herbivore at different growth stages.

PMID- 10948288
TI  - Relative contributions of aqueous and dietary uptake of hydrophobic chemicals to
      the body burden in juvenile rainbow trout.
AB  - This study assessed the relative contributions of aqueous versus dietary uptake
      of three hydrophobic chemicals, 1,2, 4-trichlorobenzene (1,2,4-TCB), 1,2,3,4,5
      pentachlorobenzene (PeCB), and 2,2',4,4',6,6'-hexachlorobiphenyl (HCBP). Juvenile
      rainbow trout (Oncorhynchus mykiss) were exposed separately to chemically spiked
      water and food for 4 days and 12 days, respectively. Chemical concentrations were
      measured in the food, water, and tissues, and this allowed calculation of uptake
      rate constants (k(1) from water exposure, k(d) from food exposure). The k(1)
      values for the three test chemicals were approximately five orders of magnitude
      greater than the k(d) values. Using these measured uptake rate constants, a
      simulation model was used to predict the relative aqueous versus dietary uptake
      when fish were exposed simultaneously to water and food contaminated with these
      hydrophobic chemicals. The model predicted for all three test chemicals that the
      two uptake routes would contribute equally to the chemical body burden in fish
      whenever the food:water chemical concentration ratio was near 10(5). However,
      using food:water chemical concentration ratios that might be expected in nature,
      the model predicted that gill uptake could account for over 98% of fish body
      burden for both 1,2,4-TCB and PeCB uptake (log K(ow) values of 3.98 and 5.03,
      respectively). For HCBP (log K(ow) of 7.55), the model predicted that the dietary
      uptake could contribute over 85% of the body burden. Thus, depending on the
      actual food:water chemical concentration ratio, aqueous uptake via the gills can
      predominate even when the chemicals have a log K(ow) value greater than 5.0. In
      addition, we confirmed that dietary uptake of hydrophobic xenobiotics increases
      with increasing log K(ow).

PMID- 10948290
TI  - Development of a bioassay to test the possible role of thiamine disturbance as a
      mechanism behind pollution-induced reproductive failures in birds.
AB  - A test system was developed to examine the effects of environmental contaminants
      on thiamine homeostasis in bird embryos. This system employs fresh chicken egg
      yolk lipids as a vehicle for use in egg injection studies. Furazolidone, an
      antibiotic suspected to interfere with thiamine metabolism, was used as a
      positive control to evaluate the utility of the test system. It was determined
      that fresh chicken egg yolk lipids were preferable over chemical vehicles as it
      resulted in lower mortality rates (16% versus 23-62%) and did not induce any
      observable effects in the embryo. Injection of 1 mg/egg of furazolidone at day 0
      of development resulted in decreased respiration followed by death, with
      mortality rates being twice as high as in carrier controls. In addition,
      transketolase activity, which was measured as an indicator of thiamine
      availability in the body, was decreased 25% in brains of 19-day-old embryos. This
      mechanism may be of importance for effects of environmental contaminants in wild
      bird populations.

PMID- 10948291
TI  - The transfer of lead (Pb) from earthworms to shrews (Myosorex varius).
AB  - Shrews (Myosorex varius) were bait-trapped close to Stellenbosch in the Western
      Cape, South Africa, and analyzed to determine the Pb content of the liver,
      kidneys, muscle tissue, brain, skull, and bone. Shrews were also fed in the
      laboratory on mince meat and Pb-contaminated live earthworms for 12-17 days and
      the Pb content compared with control shrews from the field. The Pb levels in the
      control shrews from the field were exceptionally high and exceeded levels
      generally considered to be critical for the onset of pathological symptoms in
      target organs. The shrews that were fed with Pb-contaminated earthworms had
      significantly higher Pb concentrations in their livers and kidneys than the
      control shrews. Given that Pb is bioaccumulated in earthworms, this study showed
      that predation on earthworms could constitute a major pathway for the entry of Pb
      into the food chain. M. varius could, similar to other species of shrews in other
      parts of the world, be a suitable biological monitor to study the environmental
      hazard of Pb pollution.

PMID- 10948292
TI  - Isomer-specific accumulation and toxic assessment of polychlorinated biphenyls,
      including coplanar congeners, in cetaceans from the North Pacific and Asian
      coastal waters.
AB  - To elucidate the global distribution and toxicological impacts of polychlorinated
      biphenyls (PCBs) on cetaceans, the present study determined the concentrations of
      individual PCB congeners, including toxic non-ortho (IUPAC Nos. 77, 126, 169) and
      mono-ortho (IUPAC Nos. 105, 118, 156) coplanar congeners, in the blubber of 10
      species of adult male odontocetes collected from several locations in the North
      Pacific Ocean and along coastal waters of Japan, Hong Kong, the Philippines, and
      India during 1985-1997. Total PCB concentrations in cetaceans from temperate and
      cold waters were higher than those in cetaceans from tropical regions. Residue
      levels were found to be the highest in Fraser's dolphins collected off Kii
      Peninsula, Japan, and hump-backed dolphins from Hong Kong, reflecting serious
      marine pollution by PCBs in industrialized Asian countries. Penta- and hexa
      chlorobiphenyls were the predominant PCB congeners, accounting for about 70% of
      the total PCBs. 2,3,7,8-Tetrachlorodibenzo-p-dioxin equivalents (TEQs) of non-
      and mono-ortho coplanar PCBs in the blubber of cetaceans ranged from 36 (in
      spinner dolphins from the Philippines) to 510 pg/g wet weight (in hump-backed
      dolphins from Hong Kong). Toxic evaluation of coplanar PCBs using the TEQ concept
      indicates an greater impact on cetaceans from mid-latitudes. Toxicity
      contribution of mono-ortho congener IUPAC 118 was prominent in species from high
      latitude oceans, such as the Bering Sea and the North Pacific, whereas non-ortho
      congener IUPAC 126 accounted for the highest contribution in cetaceans from lower
      latitude regions, such as the Philippines and India. The estimated TEQ
      concentrations in the blubber of some cetacean species, such as northern right
      whale dolphin and Pacific white-sided dolphin from the northern North Pacific,
      Dall's porpoise from the Japan Sea, striped dolphin off Sanriku and Fraser's
      dolphin off Kii Peninsula, Japan, hump-backed dolphin and finless porpoise from
      Hong Kong, exceeded the levels associated with immunosuppression in harbour
      seals.

PMID- 10948293
TI  - Bile duct injury during laparoscopic cholecystectomy.

PMID- 10948294
TI  - Bile duct injury during laparoscopic cholecystectomy: myth or reality of the
      learning curve?
AB  - BACKGROUND: Bile duct injury (BDI) is a severe complication of laparoscopic
      cholecystectomy (LC) that is probably related to the effects of the learning
      curve. The aim of this prospective, institutional, and longitudinal study is to
      compare the incidence of BDI during LC in relation to the progressive experience
      of surgeons. METHODS: A total of 784 LC were examined during a 6-year period.
      They were divided into the following three consecutive groups: group A (1993-94),
      group B (1995-96), and group C (1997-98). Incidence and type of BDI, experience
      of the surgeon, intra- or postoperative diagnosis, treatment performed to repair
      the injury, and early and late morbidity and mortality were evaluated. RESULTS:
      The overall incidence of BDI was 1.4%. There were three cases of transection of
      the common bile duct, four partial lesions of the bile duct, and four cystic
      leakages. The number of BDI was maintained over the three different time periods;
      there were no statistical differences in the proportion of injuries among groups.
      Most BDI were incurred by experienced surgeons. In all, 36% of BDI were
      recognized intraoperatively. Hepaticojejunostomy, direct suture over a T-tube,
      and closure of the cystic stump were done to repair BDI. There was no additional
      morbidity or mortality in the patients with BDI. CONCLUSIONS: No relation was
      found between the experience of the surgeon and the number of BDI over the
      different periods of time. Therefore, BDI during LC cannot be attributed solely
      to the learning curve.

PMID- 10948295
TI  - Laparoscopic surgery for stage III colon cancer: long-term follow-up.
AB  - BACKGROUND: The role of laparoscopic surgery in the management of colorectal
      cancer is controversial. This study was undertaken to determine the oncological
      adequacy, in terms of margins of resection, lymph node harvest, and anastomotic
      and locoregional recurrence of laparoscopic colectomy in patients with stage III
      (node-positive) colorectal cancer. METHODS: The results of laparoscopic colectomy
      in 50 consecutive patients with stage III colorectal cancer operated on at a
      single hospital between 1991 and 1998 were analyzed with respect to postoperative
      morbidity, mortality, and long-term survival by the Kaplan-Meier method.
      Methodical patient follow-up was the mainstay of the study. RESULTS: There were
      31 men (52%) and 19 women (38%) with a mean age of 67.7 years (range, 40-88). Low
      anterior resection was performed in 17 cases, abdominal perineal resection in
      five cases sigmoid colectomy in 10 cases, left hemicolectomy in six cases, right
      hemicolectomy in seven cases, transverse colectomy in one case, and subtotal
      colectomy in four cases. Conversion was necessary in three cases (6%). Major
      complications included one leak, one pelvic abscess, one perineal wound
      infection, and three anastomotic strictures early in the experience, with none in
      the past 4 years. One early death occurred due to massive stroke. Median length
      of stay was 6 days (range, 3-37). Forty-six patients were staged as CII and four
      as CI colon cancer. The average number of positive nodes was 5.1 (range, 3-58).
      The margins of resection were adequate in all patients. Follow-up ranged from 3
      to 75 months (average, 29.3; median, 24). Overall cancer-related mortality was
      34% (17 patients); three patients died of unrelated causes with no detectable
      cancer. All who died of cancer had distant disease; three of them also had pelvic
      recurrence. Mean time of death was 21.7 months. There were no anastomotic
      recurrences or trocar site implants. Overall 3- and 5-year survival was 54.5% and
      38.5%, respectively; cancer-adjusted survival was 60.8% and 49.1%. CONCLUSIONS:
      Based on this study, laparoscopic colectomy in patients with stage III colorectal
      cancer is oncologically adequate. It results in a long-term outcome comparable to
      that of traditional open surgery and is associated with low perioperative
      mortality and morbidity (lower wound infection rate, lower wound recurrences at
      trocar sites) and a shortened length of stay.

PMID- 10948296
TI  - The feasibility and accuracy of diagnostic laparoscopy in the septic ICU patient.
AB  - BACKGROUND: Systemic inflammatory response syndrome (SIRS) and sepsis of unknown
      origin are common complications of critically ill patients in the ICU. These
      patients frequently have unreliable clinical exams and are candidates for
      exploratory laparotomy. Although abdominal CT is commonly used because it is less
      invasive than laparotomy, it is often unreliable or unobtainable. Bedside
      laparoscopy is an alternative technique that may be more accurate than CT in
      selected patients and less invasive than laparotomy. METHODS: We performed
      diagnostic laparoscopy (DL) in a series of ICU patients with SIRS/septic state of
      unknown origin between May 1997 and June 1998. All patients were unstable and
      required significant respiratory and hemodynamic support. Laparoscopy was either
      performed in the ICU at the patient's bedside or in the operating room. CT scan
      of the abdomen had been performed on most of the patients who were stable enough
      to transport. Confirmation of diagnosis was obtained either by laparotomy,
      autopsy, or clinical recovery. RESULTS: Among the 17 eligible patients, 16
      underwent successful DL. Insufflation was impossible in one patient because of
      high intraabdominal pressure. Bedside evaluations were performed in 14 of the 17
      patients. There were no complications from the laparoscopy. Six patients were
      identified as positive (four intestinal ischemia, two cholecystitis); the other
      10 had negative explorations. Follow-up on two patients with negative laparoscopy
      was incomplete due to denied postmortem. Laparoscopic diagnoses were confirmed in
      the remaining 14 patients by laparotomy (six cases), postmortem (three cases), or
      recovery (five cases), with an accuracy of 100%. The overall accuracy of
      abdominal CT obtained in nine of the 14 patients was 33%. CONCLUSIONS: DL in a
      select group of critical ICU patients is safe and accurate, whereas CT scan tends
      to be inaccurate and is often unobtainable due to patient instability. Performing
      the procedure at the bedside can expedite the diagnosis, eliminate the burden for
      transfer, and save on anesthesia and operating room charges.

PMID- 10948297
TI  - Complications of laparoscopic antireflux surgery in childhood.
AB  - BACKGROUND: The aim of this study was to assess the complications associated with
      the laparoscopic treatment of gastroesophageal reflux disease (GERD) in children.
      METHODS: From March 1992 to March 1998, we used the laparoscopic approach to
      treat 289 children affected by gastroesophageal reflux disease. The patients'
      ages ranged between 4 months and 17 years (median, 4.3 years), and their body
      weight ranged between 5 and 52 kg. In 148 children (51.3%), we adopted a Nissen
      Rossetti procedure and in 141 (48.7%) a Toupet technique. RESULTS: The duration
      of surgery ranged between 40 and 180 min (median, 70). There were no deaths and
      no anesthesiological complications in our series. We recorded 15 (5.1%)
      intraoperative complications: six pleural perforations, four lesions of the
      posterior vagus nerve, two esophageal perforations, two gastric perforations, and
      one pericardiac perforation. Conversion to open surgery was necessary in only
      four cases (1.3%). We recorded 10 (3.4%) postoperative complications: one
      peritonitis due to an esophageal perforation not detected during the intervention
      that required a reoperation, five cases of herniation of the epiploon through a
      trocar orifice, three cases of dysphagia that disappeared spontaneously after a
      few months, and one case of delayed gastric emptying that subsequently required a
      pyloroplasty. We had six recurrences of GERD (2.1%). In two cases, a new
      fundoplication was performed using the laparoscopic approach; in the other four,
      the GERD was controlled with medical therapy. CONCLUSION: Our results show that
      laparoscopic fundoplication is an adequate treatment for children with GERD that
      has a low rate of complications. When severe complications do occur, they can be
      treated effectively via the laparoscopic approach.

PMID- 10948298
TI  - Macroscopic assessment of the appendix at diagnostic laparoscopy is reliable.
AB  - BACKGROUND: Healthy-looking appendixes are often removed at laparoscopy for
      suspected appendicitis. This practice may have adverse secondary effects.
      METHODS: We reviewed the literature for the years 1978 to 1998 to analyze the
      negative appendectomy rates, complication rates, the accuracy of laparoscopic
      appendix assessment, and the incidence of false negative diagnosis of
      appendicitis at surgical and gynecological laparoscopy. RESULTS: The respective
      negative appendectomy rates were 22% and 15% in studies that compared
      laparoscopic with open appendectomy. The appendix was left in situ in 37% of
      4,281 surgical diagnostic laparoscopies. There were instances of missed
      appendicitis among the 3,367 gynecological diagnostic laparoscopies performed on
      women for lower abdominal pain, and there were 188 appendectomies in this group.
      Studies comparing the macroscopic appearance of the appendix at operation with
      microscopic findings from the excised specimen had a false negative error rate of
      3%. CONCLUSIONS: Contrary to general opinion, there is no substantial evidence to
      support the assumption that the macroscopic diagnosis of appendicitis is
      unreliable. High rates of conflicting diagnoses of excision specimens suggest
      that endoappendicitis has little clinical significance. At present, negative
      appendectomy rates are considerably higher for laparoscopic appendectomy than for
      the open approach. The role of diagnostic laparoscopy in suspected appendicitis
      should be reconsidered. It may be useful in particular subgroups of patients, but
      it is no substitute for good clinical judgment. Furthermore, it is not always
      necessary to perform an incidental appendectomy.

PMID- 10948299
TI  - Laparoscopic repair of rectal prolapse: a prospective study evaluating surgical
      outcome and changes in symptoms and bowel function.
AB  - BACKGROUND: There have been few large series that have focused on the feasibility
      of the laparoscopic approach for rectal prolapse. This single-institution study
      prospectively examines the surgical outcome and changes in symptoms and bowel
      function following the laparoscopic repair of rectal prolapse. METHODS: In a
      selected group of 34 patients (total prolapse, 28; intussusception, six), 17
      patients underwent laparoscopic-assisted resection rectopexy and 17 patients
      received a laparoscopic sutured rectopexy. Preoperative and postoperative
      evaluation at 3, 6, and 12 months included assessment of the severity of anal
      incontinence, constipation, changes in constipation-related symptoms, and colonic
      transit time. RESULTS: Median operation time was 255 min (range, 180-360) in the
      resection rectopexy group and 150 min (range, 90-295) in the rectopexy alone
      group. Median postoperative hospital stay was 5 days (range, 3-15) and median
      time off work was 14 days (range, 12-21) in both groups. There were no deaths.
      Postoperative morbidity was 24%. Incontinence improved significantly regardless
      of which method was used. The main determinant of constipation was excessive
      straining at defecation. Constipation was cured in 70% of the patients in the
      rectopexy group and 64% in the resection rectopexy group. Symptoms of difficult
      evacuation improved, but the changes were significant only after resection
      rectopexy. Two patients (7%) developed recurrent total prolapse during a median
      follow-up of 2 years (range 12-60 months). CONCLUSIONS: Laparoscopic-sutured
      rectopexy and laparoscopic-assisted resection rectopexy are feasible and carry an
      acceptable morbidity rate. They eliminate prolapse and cure incontinence in the
      great majority of patients. Constipation and symptoms of difficult evacuation are
      alleviated.

PMID- 10948300
TI  - Laparoscopic ventriculoperitoneal shunt placement: a single-trocar technique.
AB  - Ventriculoperitoneal shunt (VPS) placement is an important therapeutic technique.
      Placement of the abdominal portion of VPS can be difficult in the setting of
      previous abdominal surgery, prior failure of VPS, or obesity. Even under ideal
      circumstances, standard mini-laparotomy does not allow precision in VPS
      positioning. We describe a single-port technique for VPS placement. While the
      neurosurgeon places a right frontal ventricular catheter and valve, an
      infraumbilical trocar is placed utilizing the open Hasson technique. A 12-mm
      operating laparoscope with an 8-mm channel is used to inspect the abdomen and
      identify the VPS entry site. Adhesions interfering with shunt placement can be
      lysed through the working channel of the laparoscope. Under laparoscopic
      visualization, an 18-gauge needle is introduced through a 5-mm incision in the
      right upper quadrant and the VPS tubing is tunneled to that site. A J-tipped
      guidewire is introduced, and the needle is exchanged for a dilator and peel-away
      sheath. The VPS is delivered through the sheath, which is sectioned and removed.
      An atraumatic grasper, placed through the laparoscope, directs the VPS to the
      desired intraabdominal location. Function of the VPS is assessed visually while
      compressing the valve. Suture closure of the trocar site and VPS entry site
      completes the procedure. We used this method successfully in a series of five
      patients with excellent outcome. A 14-month follow-up has revealed no failures or
      postoperative complications. This method is less invasive than mini-laparotomy,
      allows for precision placement of the abdominal portion of VPS, and confirms
      appropriate function.

PMID- 10948301
TI  - Foreign body aspiration in children.
AB  - BACKGROUND: There is still considerable controversy about the diagnostic
      procedure, the endoscopic approach, and the complication rate with foreign body
      aspiration in children. METHODS: Review of our data for 98 children suspected for
      foreign body aspiration between January 1990 and December 1998 was performed.
      RESULTS: In this data review, 78% of the children studied were younger than 2
      years. A foreign body aspiration was identified in 70%, and 67% had a definite
      history of aspiration. Predominant clinical features were fever (46%), pneumonia
      (39%), and coughing (29%). Pathologic chest radiographs were found in 84% of the
      children. Sixty-two percent of the foreign bodies were trapped in the right lung,
      and 87% were of organic in origin. In 93%, a single endoscopic procedure was
      successful in removing the foreign bodies. The mean time between aspiration and
      bronchoscopic extraction was 5.4 days (range, 1 h to 36 weeks). The procedure
      related morbidity rate was 0.96% and the mortality 0. CONCLUSIONS: Outcome and
      complications were found to depend mainly on the time the foreign body stayed in
      the tracheobronchial system. Early bronchoscopy is paramount in any case of
      suspected foreign body aspiration, and it is mandatory to increase the awareness
      of the population and medical professionals.

PMID- 10948302
TI  - The effect of carbon dioxide pneumoperitoneum on free radicals.
AB  - BACKGROUND: Carbon dioxide is usually preferred as the insufflating agent for
      laparoscopic surgery because it is readily available, noncombustible, and
      chemically stable. It is still questionable, however, if CO2 pneumoperitoneum has
      any effect on free radicals and lipid peroxidation. The purpose of this study was
      to investigate the possible effects of CO2 pneumoperitoneum on free radicals and
      lipid peroxidation in the erythrocytes of rats. METHODS: Fifty male Sprague
      Dawley rats were divided into five equal groups: controls, a sham-operation
      group, and three groups of 5, 10, or 15 mmHg pneumoperitoneum with CO2. At the
      end of the procedure, blood was collected and the erythrocytes were separated
      from the plasma. The resultant supernatant fractions of erythrocytes were assayed
      for superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA).
      RESULTS: SOD activities of the 5 and 10 mmHg pneumoperitoneum groups were
      significantly lower than those of the sham operation group. SOD activity was
      greater in the 15 mmHg pneumoperitoneum group than in any of the other groups,
      and this activity was significantly different from that seen in the 5 and 10 mmHg
      pneumoperitoneum groups (p < 0.05). No significant changes were observed in the
      CAT activities of the study groups (p > 0.05). MDA level was increased in the 5
      mmHg pneumoperitoneum group; this result was statistically different from the
      control and 15 mmHg pneumoperitoneum groups (p < 0.05). No significant
      differences were found in the CAT activities for the study groups. On the other
      hand, the SOD activities of the 5 and 10 mmHg pneumoperitoneum groups were
      significantly lower than those of the sham and the 15 mmHg pneumoperitoneum group
      (p < 0.05 for all comparisons). CONCLUSIONS: These results indicate that CO2
      pneumoperitoneum applied with 5-10 mmHg pressure increases the formation of free
      oxygen radicals by inhibiting SOD activity and that the accumulation of free
      radicals elevates the level of MDA, a metabolite of lipid peroxidation. The
      effect of CO2 pneumoperitoneum on free radicals and lipid peroxidation is
      pressure-dependent in rats. The mechanism underlying this pressure dependency is
      still under investigation.

PMID- 10948303
TI  - Endoscopic photodynamic therapy for obstructing esophageal cancer: 77 cases over
      a 2-year period.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an alternative treatment option for the
      palliation of obstructive esophageal cancer. We report our experience with PDT
      for patients presenting with inoperable, obstructing, or bleeding esophageal
      cancer. METHODS: Seventy-seven patients with inoperable, obstructing esophageal
      cancer were treated with PDT from November 1996 to July 1998. Photofrin (1.5-2.0
      mg/kg) was administered, followed by endoscopic light treatment (630 nm red dye
      laser) at 48 h. Dysphagia score (1 for no dysphagia to 5 for complete
      obstruction), dysphagia-free interval, and patient survival were assessed.
      RESULTS: Seventy-seven patients underwent 125 PDT courses. The mean dysphagia
      score at 4 weeks after PDT in 90.8% of the patients improved from 3.2 +/- 0.7 to
      1.9 +/- 0.8 (p < 0.05). PDT adequately controlled bleeding in all six patients
      who had bleeding. The most common complications after the 125 PDT courses were
      esophageal stricture (4.8%), Candida esophagitis (3.2%), symptomatic pleural
      effusion (3.2%), and sunburn (10.0%). Twenty-nine patients (38%) required more
      than one PDT course, and seven patients required placement of an expandable metal
      stent for recurrent dysphagia. The mean dysphagia-free interval was 80.3 +/- 58.2
      days. The median survival was 5.9 months. CONCLUSIONS: Photodynamic therapy is a
      safe and effective treatment for the palliation of obstructing and bleeding
      esophagus cancer.

PMID- 10948304
TI  - Laparoscopic orchiopexy without division of the spermatic vessels: can it be
      considered the procedure of choice in cases of intraabdominal testis?
AB  - BACKGROUND: Several surgical procedures have been described for the management of
      nonpalpable testis. Following a vast experience with a complete laparoscopic two
      stage Fowler-Stephens procedure, we report our experience with laparoscopic
      orchiopexy performed without dividing the spermatic vessels. METHODS: Over a 24
      month period, 70 boys with nonpalpable testes (72 overall) underwent laparoscopic
      diagnostic exploration. Twenty patients (27.8%) of this series who showed an
      intraabdominal testis underwent laparoscopic orchiopexy without sectioning the
      spermatic vessels. In seven cases, the testis was just proximal to the internal
      inguinal ring; in 13, it was in the high intraabdominal position. The technique
      consisted in sectioning the gubernaculum (when present), opening the peritoneum
      laterally to the spermatic vessels, and mobilizing the testicular vessels and the
      vas deferens in a retroperitoneal position for 8-10 cm. The testis was then
      brought down into the scrotum through the internal inguinal ring (11 cases), if
      this was open, or through a neo-inguinal ring (nine cases) created medially to
      the epigastric vessels. In every case, we closed the inguinal ring at the end of
      the operation using one or two detached sutures. RESULTS: Operating time ranged
      between 40 and 75 min (median, 55). All the testes were successfully brought down
      into the scrotum. We had only one (5%) intraoperative complication. In the second
      patient treated with this procedure, there was an iatrogenic rupture of the
      spermatic vessels due to excessive traction. CONCLUSION: On the basis of our
      experience, we believe that laparoscopic orchiopexy without division of the
      spermatic vessels should be the treatment of choice in the management of
      nonpalpable testes, because it does not affect normal testicular vascularization
      and is minimally invasive. A blunt dissection and a delicate manipulation of the
      testis without excessive traction are the best ways to avoid any kind of
      complication.

PMID- 10948305
TI  - Laparoscopic cholecystectomy: what does affect the outcome? A retrospective
      multifactorial regression analysis.
AB  - BACKGROUND: The association between various factors and the postoperative outcome
      has not been thoroughly studied in laparoscopic cholecystectomy (LC). The aim of
      this retrospective study was to determine which factors significantly affect
      patients outcome after LC. METHODS: The medical and operative records of all
      consecutive patients who underwent LC at our institution from 1991 to 1996 were
      reviewed. The effect of age, medical and surgical history, duration of procedure,
      and setup (urgent or elective) on the postoperative complication rate and on the
      length of postoperative hospital stay (LOS) were analyzed using multiple linear
      regression and logistic regression analysis. Overall, 601 patients were included
      in the study. RESULTS: The factors that significantly prolonged LOS were age (p =
      0.0145), acute cholecystitis (p = 0.0006), history of ischemic heart disease (p =
      0.0332), and duration of procedure (p < 0.0001). A significantly higher
      postoperative morbidity rate was noted in patients who had a procedure longer
      then 2 h than in patients whose surgery required less the 2 h (13.6% vs 3.6%,
      respectively; p < 0.0001). Similarly, higher morbidity was noted in elderly
      patients than in younger patients (16% vs 6.1%; p = 0.0005). Other factors that
      significantly increased postoperative morbidity included acute cholecystitis (p =
      0.023), a history of cholangitis (p = 0.018), and diabetes (p = 0.05).
      CONCLUSIONS: According to this study, advanced age, longer duration of procedure,
      and acute cholecystitis significantly increase both the postoperative morbidity
      and the LOS. History of ischemic heart disease significantly increases LOS, but
      does not increase morbidity after LC.

PMID- 10948306
TI  - Ultrasound-based volumetric evaluation of fluid retention after inguinal hernia
      repair.
AB  - BACKGROUND: Daily routine has shown that there are differences between the
      aspirated volumes of subcutaneous liquid retention after inguinal hernia repair
      and the results of sonographic-based volumetry using the standard rotating
      ellipsoid formula. METHODS: In 83 patients, subcutaneous fluid retention after
      Shouldice repair was visualized by ultrasound and calculated as cuboid, cylinder,
      and rotating ellipsoid, respectively. The results were compared to the aspirated
      volume. Data were analyzed retrospectively. RESULTS: The volume obtained by
      percutaneous punction averaged 12.18 +/- 1.50 ml. The calculated volumes were
      distinctly less: cuboid, 11.98 +/- 1.59 ml; cylinder, 10.26 +/- 1.45 ml; rotating
      ellipsoid, 5.99 +/- 0.80 ml. We found different coefficients of regression for
      the aspirated and the calculated volumes (cuboid; 0.75; cylinder; 0.82; rotating
      ellipsoid; 1.50). The coefficients of correlation, however, were 0.79 for all
      modes of calculation. CONCLUSION: Because its results were closest to the
      aspirated volumes, we recommend the cuboid formula for the ultrasound-based
      calculation of liquid retention after inguinal hernia repair.

PMID- 10948307
TI  - Anastomotic stenoses occurring after circular stapling in esophageal cancer
      surgery.
AB  - BACKGROUND: Circular staplers have reduced the incidence of anastomotic leaks in
      esophagovisceral anastomosis. However, the prevalence of stenosis is greater with
      staplers than with manual suturing. The aim of this study was to analyze
      potential risk factors for the onset of anastomotic stenoses and to evaluate
      their treatment and final outcome. METHODS: Between 1990 and 1995, 187 patients
      underwent esophagectomy and esophagogastrostomy with anastomosis performed inside
      the chest using a circular stapler. RESULTS: Twenty-three patients (12.3%)
      developed an anastomotic stenosis. The incidence of strictures was inversely
      related to the diameter of the stapler. Concomitant cardiovascular diseases;
      morphofunctional disorders of the tubulized stomach, such as those related to
      duodenogastric reflux; and neoadjuvant chemotherapy were also recognized as
      significant risk factors. Endoscopic dilatations proved safe and were effective
      in the treatment of most anastomotic stenoses. CONCLUSIONS: To reduce the risk of
      anastomotic stenosis after stapled intrathoracic esophagogastrostomy, adequate
      vascularization of the viscera being anastomized should be maintained, and it is
      mandatory to use the largest circular stapler suitable. Furthermore, it is
      essential to reduce the negative inflammation-inducing effects of
      duodenogastroesophageal reflux to a minimum. Endoscopic dilatations are safe and
      effective in curing the great majority of anastomotic stenoses.

PMID- 10948308
TI  - Technical advances toward interactive image-guided laparoscopic surgery.
AB  - BACKGROUND: Laparoscopic surgery uses real-time video to display the operative
      field. Interactive image-guided surgery (IIGS) is the real-time display of
      surgical instrument location on corresponding computed tomography (CT) scans or
      magnetic resonance images (MRI). We hypothesize that laparoscopic IIGS
      technologies can be combined to offer guidance for general surgery and, in
      particular, hepatic procedures. Tumor information determined from CT imaging can
      be overlayed onto laparoscopic video imaging to allow more precise resection or
      ablation. METHODS: We mapped three-dimensional (3D) physical space to 2D
      laparoscopic video space using a common mathematical formula. Inherent
      distortions present in the video images were quantified and then corrected to
      determine their effect on this 3D to 2D mapping. RESULTS: Errors in mapping 3D
      physical space to 2D video image space ranged from 0.65 to 2.75 mm. CONCLUSIONS:
      Laparoscopic IIGS allows accurate (<3.0 mm) confirmation of 3D physical space
      points on video images. This in combination with accurately tracked instruments
      and an appropriate display may facilitate enhanced image guidance during
      laparoscopy.

PMID- 10948310
TI  - New instrumentation for video-assisted anterior spine release.
AB  - Endoscopic surgery in the area of orthopedics has been evolving, particularly in
      spine surgery. We describe the clinical outcome of thoracoscopic anterior spine
      release using new instruments. A harmonic scalpel (HS) with a 5-mm hook dissector
      was used to dissect the spine and rib and to coagulate and transect the vascular
      bundles. A rib dissector and resector were used for excision of the rib to be
      implanted in the disk spaces. We treated scoliosis in four patients (three male,
      one female) with a mean age of 19.5 +/- 4.5 years and thoracolumbar kyphosis in a
      16-year-old male patient. A mean number of 6.5 +/- 2.5 vertebrae with scoliosis
      and four vertebrae with kyphosis were released. In all cases, division of the
      vascular bundle and exposure of the spine were completed using only the HS, and
      excision of a rib segment was performed via a port incision using only the rib
      dissector and resector. The mean duration of thoracoscopic anterior release was
      92 +/- 28 min. Blood loss was minimal during and after surgery. Thoracoscopic
      anterior spine release can be facilitated by the new instruments described above.

PMID- 10948312
TI  - A snare retractor for thoracolaparoscopic surgery.

PMID- 10948311
TI  - Reinventing the culdoscope.
AB  - The purpose of this study was to reassess culdoscopic visualization of the female
      pelvis using a small flexible fiberoptic choledochoscope introduced via a
      disposable trochar system. A disposable 5-mm retractable laparoscopic trochar was
      used to gain access to the peritoneal cavity via the posterior fornix of the
      vagina. A 4.9-mm flexible choledochoscope then was introduced through this
      trochar to visualize the pelvic organs. The initial procedures were performed
      with the patient under general anesthesia using direct laparoscopic visualization
      of the cul-de-sac. Subsequent procedures were performed on women who were awake,
      using local anesthesia and sedation with the patients in a knee-chest position.
      In this study, 18 women taken to the operating room for a planned transvaginal
      hysterectomy or laparoscopically assisted vaginal hysterectomy underwent flexible
      culdoscopy. Three procedures were performed with the patients under general
      anesthesia using direct laparoscopic visualization, and 15 procedures were
      performed in a blind fashion with the patient awake in a knee-chest position. The
      average Quetelet Index was 31.2 (range, 22.8-43.1). Of the 18 procedures, 16 were
      successful in adequately visualizing the pelvic organs. There were no significant
      complications from the procedures, and no injury to adjacent organs. Culdoscopy
      with a small flexible scope can be performed safely in awake patients, providing
      adequate visualization of the female pelvis.

PMID- 10948313
TI  - Guidelines for training in diagnostic and therapeutic endoscopic retrograde
      cholangiopancreatography (ECRP). Society of American Gastrointestinal Endoscopic
      Surgeons (SAGES).

PMID- 10948314
TI  - Granting of endoscopic ultrasonography privileges for surgeons. Society of
      American Gastrointestinal Endoscopic Surgeons (SAGES).

PMID- 10948317
TI  - BrdUrd-induced radiosensitization of two human tumour cell lines at iso-levels of
      incorporation.
AB  - Bromodeoxyuridine (BrdUrd)-induced radiosensitization of two different tumour
      cell lines was compared at equal levels of thymidine replacement. Human lung
      carcinoma cells (SW-1573) and human colorectal carcinoma cells (RKO) were grown
      for 48 h in the presence of respectively 1 microM BrdUrd and 4 microM of BrdUrd
      in order to obtain equal levels of BrdUrd into the DNA. In SW cells the level of
      thymidine replacement by BrdUrd was 6.7+/-0.5% and in RKO cells this was 7.1+/
      0.8. Cell survival after irradiation with single doses up to 8 Gy, was determined
      with clonogenic assay. The magnitude of BrdUrd-induced radiosensitization was
      determined by analyzing radiation-dose survival curves with the linear-quadratic
      formula [S(D)/S(0)=exp-(alphaD+betaD2)]. In the SW cells BrdUrd
      radiosensitization led to a significant increase of the linear parameter, alpha,
      determining the initial slope of the survival curves, by a factor of about 2. In
      the RKO cells BrdUrd increased the value of alpha by a factor 1.4. This suggests
      that repair of potentially lethal damage (PLD) is inhibited. In both cell lines
      the quadratic term, beta, strongly influencing the high dose region of the
      survival curves, was not altered by sensitization by BrdUrd. The increase of
      alpha is of interest for clinical applications as BrdUrd sensitizes tumour cells
      after low doses of radiation.

PMID- 10948316
TI  - Prognostic significance of mutations in the p53 gene in superficial bladder
      cancer.
AB  - Bladder tumors as the most common urologic malignancy present mostly as
      superficial transitional cell carcinoma. Many patients with superficial bladder
      cancer have a good prognosis, however, may develop recurrences or progress to
      muscle invasive or metastatic disease. It is therefore important to find new
      markers associated with the biological behaviour of an individual tumor for
      identifying patients at risk for disease progression. Previous reports on the
      prognostic significance of p53 alterations in bladder tumors revealed conflicting
      results. The aim of our study was to evaluate p53 mutation analysis as an
      effective concept for the characterization of subsets of superficial bladder
      tumors differing in biological aggressiveness. Screening 66 amplified DNA from
      micro-dissected tumor cells by direct genomic sequencing p53 alterations were
      detected in 12%. We found no association between p53 status and tumor stage but a
      tendency to a higher mutation rate in more malignant tumors (G2 and G3) compared
      to G1 tumors and a higher recurrence rate in patients with a p53 mutation in the
      primary tumor after 24 months follow-up. We conclude a general low incidence of
      p53 mutations in superficial bladder cancer. Detectable p53 damage might be
      related to a more aggressive phenotype and a higher recurrence risk. Our results
      are discussed in the context of other studies reviewed from 1995-2000.

PMID- 10948318
TI  - Low radon doses sensitize MCF-7 human breast cancer cells to taxol.
AB  - We studied whether human breast cancer cells show increased sensitivity to the
      chemotherapeutic agent taxol when they have been treated with low radiation doses
      (1.7-3.2 x 10(-3) Gy) from the gas radon. To this end, MCF-7 cells were
      cultivated in a medium either with or without dissolved radon for 3 days and then
      exposed to taxol (50 nM). Cells exposed to low doses of radon and then to a
      concentration of 50 nM of taxol exhibit a lower proliferation rate and a lower
      viability than cells treated with the same concentration of taxol but not
      irradiated. These findings indicate an important interaction of radon and taxol
      in the inhibition of MCF-7 cell growth.

PMID- 10948320
TI  - An antibody assay predictive of BRCA1 mutations in ovarian tumors and normal
      tissue.
AB  - To determine whether immunohistochemistry can identify BRCA1 mutations,
      immunohistochemical (IH) analysis was undertaken on paraffin sections of paired
      ovarian cancer and normal tissue using antibodies against both terminal regions
      of the BRCA1 protein. Ten patients at risk for BRCA1 mutations were studied. The
      results of BRCA1 mutation analysis and IH were compared. In tumor, IH correctly
      identified the presence or absence of loss of heterozygosity in all specimens. In
      all uninvolved specimens, IH correctly identified the presence or absence of a
      germline mutation. The sensitivity, specificity, positive and negative predictive
      values were 100% suggesting promise as a rapid and inexpensive screen.

PMID- 10948319
TI  - Enhancement of immunohistochemical reactivity for thymidine phosphorylase in
      breast carcinoma cells after administration of docetaxel as a neoadjuvant
      chemotherapy in advanced breast cancer patients.
AB  - For the purpose of demonstrating possible effects of docetaxel on thymidine
      phosphorylase (TP) activity in human breast carcinoma, we examined breast
      carcinoma tissues pre- and post-administration of docetaxel, by an
      immunohistochemical method using an anti-TP monoclonal antibody. Eight patients
      with advanced breast carcinoma were initially treated with 3 cycles of 60 mg/m2
      of docetaxel once every 3 weeks after incisional biopsy of tumors, and following
      3 cycles of docetaxel, they underwent mastectomy with axillary dissection. Grades
      of immunohistochemical reactivity for TP of carcinoma cells in pre- and post
      treatment specimens were compared. Five biopsy specimens (62.5%) were positive
      for TP. After administration of docetaxel, 6 of 8 cases (75.0%) revealed
      significant enhancement of reactivity for TP. Increased reactivity was recognized
      diffusely as well as focally in carcinoma tissues. From these results, we believe
      that administration of docetaxel to breast cancer patients evokes enhancement of
      immunohistochemical reactivity for TP in breast carcinoma cells in situ.
      Furthermore, we consider that docetaxel treatment might improve efficacy of
      additional doxifluridine and capecitabine therapy.

PMID- 10948321
TI  - Immunohistochemical analysis of BRCA2 expression in normal human buccal cells.
AB  - Previously we demonstrated that protein coded by the BRCA1 gene was expressed in
      normal human buccal cells. The present study confirmed that BRCA2 protein was
      similarly expressed in these cells. Messenger RNA for BRCA2 was detected with
      sequential use of two primer sets. Pooled cell samples from healthy donors
      reacted strongly with two commercially available antibodies, I17 and C15.
      Immunoreactivity was present in both cytoplasmic and nuclear compartments. We
      conclude buccal cells will provide a suitable model for exploration of normal
      BRCA function.

PMID- 10948322
TI  - Comparative assessment of MHC antigen expression in bladder and testis tumour
      biopsies and established urological tumour cell lines: the relevance of cytokine
      and gene transfection for correction of defective MHC antigens.
AB  - The aim of this study using radio-binding (RB), peroxidase-anti-peroxidase (PAP)
      and immunoprecipitation (IP) techniques was to investigate the pattern of major
      histocompatibility complex (MHC) antigen expression in urological malignancies
      and to compare the results with those seen in established urological human tumour
      cell lines. The results showed that using PAP technique, the percent bladder
      cases showing complete loss or cases with greater than 90% of tumour cells
      negative with W6/32 (detects all class I antigens), HC10 (detects free heavy
      chain) and BMM.1 (detects beta2-mirogobulin) monoclonal antibodies (Mab) were
      16%, 44% and 2% respectively. In a subgroup of 37 cases, the intensity of MHC
      class II antigen expression for strong, weak and negative cases were 9 (24%), 8
      (22%) and 20 (54%) respectively. The expression for class I antigens on testis
      tumours was mainly negative and when positive, it was present in a small percent
      of tumour cells. This was also observed for class II antigens where only 8% of
      cases showed some degree of positivity. Using RB technique, 10 of 12 (85%) of
      tumour lines expressed class I antigens spontaneously and following interferon
      gamma (IFNgamma) stimulation, the 2 negative lines one testis (Tera I) and one
      bladder (Fen) remained negative and 2 lines (both testis lines Tera II and
      Ep2102) showed a significant class I up-regulation. None of the lines expressed
      class II antigens spontaneously and following IFNgamma stimulation, 8 of 12 (66%)
      were induced. The absence of class I and II antigens in the negative lines was
      confirmed using IP technique. In the case of one class I negative bladder cell
      line i.e. Fen, the biochemical analysis showed the absence of beta2-m gene
      product which could not be restored by IFNgamma stimulation. However,
      transfection of the cells with beta2-m gene resulted in the expression of fully
      assembled class I antigens, indicating that the loss of antigens was due to the
      absence of functional beta2-m gene. These results indicated the similarity
      between the pattern of expression of MHC antigens on tumour biopsies and
      established tumour cell lines. They also demonstrated that both cytokine
      stimulation and gene transfection could be used to correct defective class I
      antigens in tumour cell lines. These approaches might have important implications
      for pre-selection of bladder cancer patients for cytokine or gene therapies.

PMID- 10948323
TI  - Octreotide treatment suppresses malignant somatotrophic pituitary tumor cell
      growth in rats.
AB  - We have recently established an in vitro cell line (metastatic mGH3) derived from
      lymph node metastases of the rat pituitary somatotroph. Here we examined the in
      vivo effects of octreotide, a somatostatin analog, against malignant pituitary
      tumors. Wistar-Furth rats (n=8) were inoculated subcutaneously with mGH3 cells
      while control rats received injections of equal volumes of the vehicle only. Four
      rats were treated with octreotide three times daily while another group of four
      rats were treated with saline only. After 6 weeks of treatment, histopathological
      and immunohistological analyses were performed. The tumor weights of rats treated
      with octreotide were significantly lighter than those of untreated rats. All rats
      implanted mGH3, but not administered treatment, developed inguinal lymph node
      metastases, whereas none of those implanted mGH3 and treated with octreotide
      developed such metastases. The proportion of PCNA-stained tumor cells was higher
      in tumors of untreated rats than in those of octreotide-treated rats. However,
      the proportion of apoptotic cells in the tumor was not different between treated
      and untreated rats. Our results suggest that octreotide might be potentially
      effective for invasive and malignant human pituitary tumors by regulating the
      tumor cell cycle.

PMID- 10948324
TI  - Apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas
      induced by preoperative administration of 5-fluorouracil.
AB  - The purpose of this study was to examine the correlations among enhancement of
      apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas
      induced by preoperative oral administration of 5-fluorouracil (5-FU). The
      occurrence of spontaneous apoptotic cell death in 42 patients with gastric
      carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was
      examined by polymerase chain reaction-single strand confirmation polymorphism and
      sequencing. Fourteen patients received oral administration of 5-FU at 300
      mg/body/day for 7 days preoperatively. For detection of apoptotic cells,
      apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl
      transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method,
      on gastric carcinoma lesions based on the endoscopic findings before
      administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax
      gene and proliferating cell nuclear antigen (PCNA) were also examined by
      immunohistochemical staining. On preoperative biopsy, p53 point mutation was
      observed in 14 of the 42 tumors. The immunohistochemical staining status and
      point mutation of p53 gene (positive or negative) were identical in 32 of the 42
      tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53
      negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a
      significant association was not recognized between p53 expression and AI. In the
      preoperative administration group, the PCNA labeling index was significantly
      higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs.
      35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was
      significantly more accelerated in p53-negative staining (n=6) than in p53
      positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs.
      1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant
      correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of
      p53 and PCNA stainings in biopsy specimens appears to be a well-characterized
      indicator of sensitivity of chemotherapy in gastric carcinomas.

PMID- 10948325
TI  - The effect of an oral administration of Lactobacillus casei strain shirota on
      azoxymethane-induced colonic aberrant crypt foci and colon cancer in the rat.
AB  - The preventive effect of oral administration of viable Lactobacillus casei strain
      Shirota (LcS) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and
      colon cancers in the rat was investigated. The study consisted of two
      experiments; in a short-term experiment (Exp-I), the inhibitory effect of 8- and
      12-week treatments with LcS. Forty rats each received weekly a subcutaneous
      injection of AOM at a dose of 15 mg/kg of body weight for 5 weeks. Eight and
      twelve weeks after the start of the carcinogen treatment, each subgroup of rats
      were sacrificed, and the colon and the mesenteric lymph nodes (MLN) were removed.
      The number of ACFs and the surface marker of lymphocytes derived from the MLN
      were investigated. The large ACF (those comprising four or more aberrant crypts
      per focus) had significantly decreased in the rats which had consumed the LcS
      diet. And oral administration of viable LcS significantly recovered CD8 positive
      lymphocytes to the levels in the control group. In a long-term experiment (Exp
      II), 30 rats each received weekly a subcutaneous injection of AOM at a dose of 7.
      4 mg/kg of body weight for 10 weeks. Twenty-five weeks after the start of the
      carcinogen treatment, each subgroup of rats were sacrificed, and the colon were
      removed. The number and incidence of colon cancers were investigated. The number
      of rats with colon cancers and the number of colon cancers per rat, were
      significantly decreased in the rats which had consumed the LcS diet. LcS
      inhibited chemically-induced colon carcinogenesis in the rat. CD8 positive T
      lymphocytes may play a key role in the preventive effect against colon
      carcinogenesis.

PMID- 10948326
TI  - Morphologic progression in depressed-type colorectal cancers.
AB  - To clarify the morphologic progression pattern of colorectal cancers of the
      depressed-type, we correlated colonoscopic appearance of 65 such tumors with
      depth of invasion. The assessed colonoscopic findings included expansile
      appearance, depth of surface depression, irregularity of the base of the
      depression and mucosal folds converging toward the tumor. Colonoscopic findings
      of submucosal cancers and cancers with invasion of the muscularis propria were
      retrospectively reviewed. We found progression of these cancers to be associated
      with deeper depression, greater expansion, and more irregularity of shape as
      invasion progressed and mucosal folds increasingly converged toward the tumor.
      Colonoscopic findings (including expansile appearance, depth of surface
      depression, irregularity of the depression, and mucosal fold convergence toward
      the tumor) correlate with morphologic progression in depressed-type colorectal
      cancers.

PMID- 10948327
TI  - Immunohistochemical telomeric-repeat binding factor-1 expression in
      gastrointestinal tumors.
AB  - The maintenance of telomere length has been hypothesized to be involved in the
      early steps of cancerogenesis. A physiologic modulation of telomere maintenance
      is exerted by TRF1 (telomeric-repeat binding factor-1), which deletion permits
      telomere elongation. Gastrointestinal neoplastic (n=19) and non-neoplastic
      tissues (six inflammatory disease and six normal mucosa distant from tumor at
      least 5 cm) were studied, by immunohistochemistry, for TRF1 expression, by using
      a polyclonal antibody anti-TRF1. Differentiated and not proliferating epithelial
      secretory cells (Ki67 and p53 negative cells) were stained by anti-TRF1, which
      did not stain tumor cells in all cases but one (p<0.0001). p53 was expressed by
      26% of tumor cases. Inflammatory gastrointestinal non-tumor tissues showed lower
      expression of TRF1 in epithelial secreting cells compared to normal tissues
      (p=0.008). These preliminary data suggest that down-regulation of the TRF1
      expression in tumor cells may be involved in cell immortalization as an initial
      step in gastrointestinal carcinogenesis (before p53 alteration), and may open new
      perspectives, when confirmed, in gastrointestinal tumor prognosis.

PMID- 10948328
TI  - The biological and clinicopathological characteristics of right-sided colon
      cancer.
AB  - The biological characteristics of right-sided colon cancer were examined in 74
      colon cancers with regard to clinicopathological parameters, proliferative
      activity and p53 expression. Significant differences between right-sided and left
      sided colon cancer were found in age, tumor size, histological type and lymphatic
      vessel invasion. The proliferating cell nuclear antigen labeling index did not
      significantly differ between the two cancers. The frequency of p53 overexpression
      was lower in the former than in the latter. The results suggested that right
      sided colon cancer did not differ from left-sided colon cancer in proliferative
      activity except for its tendency to be locally advanced and to differ in
      carcinogenesis.

PMID- 10948329
TI  - Molecular cloning and characterization of FX3, a novel zinc-finger protein.
AB  - In a screen for cyclin G1 interacting proteins using the yeast two-hybrid system,
      we identified a cDNA clone encoding a novel zinc-finger protein. In addition to a
      C-terminal zinc-finger domain, the 18 kDa protein, designated FX3, contains a
      bipartite nuclear targeting sequence and a number of putative protein kinase
      phosphorylation sites. The physical interaction of FX3 with cyclin G1 was
      confirmed in vitro by co-immunoprecipitation. Further studies demonstrated that
      the zinc-finger domain is not required for the observed interaction between FX3
      and cyclin G1. FX3 is an essential gene expressed in numerous human tissues, with
      the highest levels observed in the liver.

PMID- 10948330
TI  - Telomerase activity in gynecological tumors.
AB  - The aim of this study was to define the clinical implications of semi
      quantitative telomerase activity in gynecological tumors by comparing the
      telomerase activity of cancerous lesion and the adjacent non-cancerous lesion. In
      118 cases of gynecologic tumors, including 41 uterine cervical tumors, 43 uterine
      body tumors and 34 ovarian tumors, telomerase activities were determined using
      TRAPeze telomerase detection kit for the extension reaction of the telomere
      sequence and the PCR reaction for amplification of the sequence, and using
      fluorecence-based telomere repeat amplification protocol (F-TRAP) method for the
      detection. In all gynecologic cancers examined, telomerase activity of the
      cancerous lesion was significantly higher than that of the non-cancerous lesion.
      Telomerase activity in the uterine cervix increased in the following order of the
      normal uterine cervix, cervical dysplasia and cervical cancer. Regarding the
      endometrial cancer, telomerase activity at the primary lesion in patients with
      lymph node metastases was significantly higher than that in patients without
      lymph node metastases. When telomerase activity was compared by histologic
      subtypes of the ovarian cancer, clear cell adenocarcinoma showed significantly
      lower telomerase activity than the other subtypes, especially endometrioid
      adenocarcinoma. In all gynecologic cancers examined, there was no clear
      correlation between the telomerase activity and age at diagnosis or age of
      menopause. Although all tumors with 100 units or more telomerase activity were
      cancerous, the sensitivity was 39% in cervical cancer, 41% in endometrial cancer
      and 21% in ovarian cancer, respectively. Cervical intraepithelial neoplasia (CIN)
      had already increased telomerase activity and endometrial cancer with lymph node
      metastases had also greater activity than that without lymph node metastases.
      Although telomerase activity in ovarian cancer tended to increase as stage
      advances, it is noteworthy that clear cell adenocarcinoma showed significantly
      lower telomerase activity than endometrioid adenocarcinoma.

PMID- 10948331
TI  - Myofibroblasts at the tumor border of invasive gastric carcinomas: with special
      reference to histological type and tumor depth.
AB  - In order to elucidate the role of alpha-smooth muscle actin (ASMA)-positive
      stromal cells, namely myofibroblasts (MFs), in invasive growth of gastric
      carcinomas (GCs), we examined the number of MFs at the deep border (DB) of GCs.
      In total 78 invasive GCs (48 intestinal type GCs and 30 diffuse type GCs) were
      examined immunohistochemically, and analyzed from the view point of tumor depth
      and histological type. In the intestinal type GCs examined, both the GCs confined
      to the submucosa and muscularis propria had none or a small number of MFs at the
      tumor border facing the submucosa (smDB) and muscularis propria (mpDB),
      respectively; whereas the GCs invading the subserosa had a moderate or large
      number of MFs at the tumor border facing the subserosa (ssDB) (p<0. 05).
      Regardless of tumor depth, the diffuse type GCs examined generally had none or a
      small number of MFs at the smDB, mpDB and ssDB, respectively. There is a
      possibility that intestinal type GCs invading the subserosa showing tubular and
      papillary structure may induce myofibroblastic transformation of gastric
      subserosal stromal fibroblastic cells.

PMID- 10948332
TI  - A potentially novel peptidase, resembling but distinct from neutrophil elastase,
      produced by carcinoma cells.
AB  - Neutrophil elastase (NE) is the only neutral protease that can degrade broad
      substrates of extracellular matrix components. In the present study, we describe
      the NE-like molecule expressed in many carcinoma cells, which has similar
      activity to NE and pancreatic elastase, but is immunologically different from NE,
      and is not inhibited by NE or pancreatic elastase inhibitor at all. Intracellular
      activity of NE or pancreatic elastase and immunological reactivity of NE in ten
      carcinoma cell lines and freshly purified neutrophils were measured by CellProbe
      and enzyme immunoassay, respectively. The NE and pancreatic inhibitory effect to
      the extracts of the ten cell lines was further examined using NE and pancreatic
      elastase inhibitor (ONO-5046.Na). Only two carcinoma cell lines out of ten had
      low immunoreactive NE, whereas neutrophils had high immunoreactivity in the
      extract. Flow cytometric analyses demonstrated that five out of 11 carcinoma cell
      lines had a high degrading activity of Ala-Ala-Pro-Val site in more than half of
      the population. SUIT-2 had the highest activity, but had no immunoreactivity for
      NE. Furthermore, the NE-like activity in the SUIT-2 cells was not inhibited by
      ONO-5046.Na. The present study demonstrated the NE-like molecule expressed in
      many types of carcinoma cells, which is potentially a new and specific protease
      produced by cancer cells. It would be of great interest to identify this NE-like
      molecule specific to the tumor, leading to a possible promising treatment of
      advanced carcinomas.

PMID- 10948333
TI  - Low specificity of cytokeratin 19 mRNA expression in the peripheral blood cells
      from patients with ovarian tumors.
AB  - We examined CK19 mRNA expression in the peripheral blood mononuclear cells (PBMC)
      from patients with ovarian tumor by reverse transcriptase-polymerase chain
      reaction (RT-PCR) using primers which did not cross-amplify pseudogenes of CK19
      gene. The incidence of positive CK19 mRNA expression in healthy individuals,
      benign ovarian tumor patients and ovarian cancer patients were 60% (12/20), 71%
      (10/14) and 84% (21/25), respectively. Although the frequency of positive CK19
      mRNA expression in PBMC from ovarian tumor patients was higher than that from
      healthy individuals, there was no statistically significant difference between
      the frequencies. Moreover, one healthy control showed CK19 mRNA expression only
      in her menstrual period, not in her proliferative phase or secretory phase. These
      results suggested that CK19 is not a suitable target to detect the presence of
      tumor cells in the PBMC from patients with ovarian tumors.

PMID- 10948334
TI  - An in vitro chemosensitivity test for gastric cancer using collagen gel droplet
      embedded culture.
AB  - Collagen gel droplet embedded culture drug sensitivity test (CD-DST) was applied
      to 33 patients with gastric cancer (30 primary tumors, 12 metastatic tumors and
      25 biopsy specimens). Evaluable rates by CD-DST were 80% for primary tumors, 75%
      for metastatic tumors and 72% for biopsy specimens. Chemosensitivities of primary
      tumors were: 5-fluorouracil 25%, mitomycin C 17%, cisplatin 13%, adriamycin 17%,
      etoposide 21%. Chemosensitivities of metastatic tumors were lower than those of
      primary tumors. In 4 out of 6 patients who had measurable lesions, clinical
      responses to chemotherapy were predictable by CD-DST.

PMID- 10948335
TI  - Therapy and survival in male breast carcinoma: A retrospective analysis of 50
      cases.
AB  - The relationship between therapy and overall survival was retrospectively
      investigated in 50 patients with primary male breast carcinoma. Forty-five had
      radical or modified radical mastectomy and 5 simple mastectomy. Thirty-five
      received adjuvant post-operative therapy, including radiation, hormone and
      chemotherapy, given separately or in combination. The mean follow-up period was
      67 (range, 1-230) months. The median survival was 33 months for patients
      receiving surgery alone and 86 months for those who also had adjuvant therapy
      (p=0.003). No difference in survival was found between simple or radical/modified
      radical mastectomy, nor among the various types of adjuvant therapy. Adjuvant
      therapy was most effective in large size, node positive and poorly differentiated
      tumors, and retained independent prognostic significance in multivariate
      analysis. With the limitation due to the small number of cases, our data suggest
      that adjuvant therapy may improve survival in males with cancer of the breast.

PMID- 10948336
TI  - Overexpression of p53 and rare genetic mutation in mesenchymal chondrosarcoma.
AB  - Mesenchymal chondrosarcoma is extremely rare and accounts for less than 2% of all
      chondrosarcomas. The pathogenesis and the molecular genetic events which
      contribute to the development of mesenchymal chondrosarcoma are not well
      elucidated, due in part to the lack of sufficient tumor tissue available. To
      characterize the involvement of the p53 gene abnormality in this disease, we
      analyzed expression and sequence alteration of p53 by immunohistochemical
      analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays
      of the gene in 33 paraffin-embedded tissue specimens. Immunohistochemical
      analysis demonstrated that 19 (61.3%) of 31 had nuclear overexpression of p53
      while 7 (22.6%) showed cytoplasmic expression. The remaining 5 (16.1%) were
      negative for p53 staining. The nuclear positivity of p53 was observed within a
      range of 22-64% (mean 37.3%) of tumor cells and showed a positive staining in
      mesenchymal components as well as chondroid components. Quantitative DNA/PCR
      analysis revealed that 6 (18.2%) of the 33 specimens carried significantly
      reduced or undetectably low levels of p53 indicating the genomic deletion of the
      gene in these tumors. In contrast, however, DNA/PCR-SSCP analysis failed to
      detect any types of mutations resulting in amino acid substitution within exons 5
      9 regions of the gene. Taken together, our data suggests that genetic alteration
      of p53 is a relatively rare event in mesenchymal chondrosarcomas but substantial
      fraction of this type of tumors carries abnormal overexpression of p53, which
      might result from as yet unidentified epigenetic mechanism(s).

PMID- 10948337
TI  - Silk protein, sericin, suppresses colon carcinogenesis induced by 1,2
      dimethylhydrazine in mice.
AB  - Male 5-week old ICR mice were examined for the effect of feeding silk protein,
      sericin on colon carcinogenesis. In experiment 1, mice were fed the diets
      supplemented with 1.5% or 3% sericin for five weeks, and given weekly injections
      of 1,2-dimethylhydrazine (DMH) for the initial three weeks. Supplemental sericin
      caused a dose-dependent decrease in the development of colonic aberrant crypt
      foci. In experiment 2, mice were fed the diet supplemented with 3% sericin for
      115 days, and given weekly injections of DMH for the initial ten weeks. The
      incidence and number of colon tumors were suppressed by consumption of sericin.
      The results suggest a potential usefulness of sericin as a chemopreventive agent
      for colon carcinogenesis.

PMID- 10948338
TI  - Two different types of concomitant resistance induced by murine tumors:
      morphological aspects and intrinsic mechanisms.
AB  - Concomitant resistance (CR) is the phenomenon according to which a tumor-bearing
      host inhibits the growth of a secondary implant of the same tumor at a distant
      site. Confirming and extending previous results of our laboratory, histological
      studies have revealed that two temporally separate peaks of CR can be detected
      throughout tumor evolution. The first peak induced by immunogenic small tumors,
      in euthymic but not in nude mice, is associated with extensive necrosis of the
      secondary tumor implant and a profuse infiltration of polymorphonuclear
      granulocytes and mononuclear cells resulting in its final destruction; these
      features correspond to a typical immunological rejection. The second peak of CR
      induced by both immunogenic and non-immunogenic large tumors, in euthymic as well
      as in nude mice, is characterized by a dormant tumor stage with scarce or null
      mononuclear infiltration, associated with a significant reduction of tumor
      mitotic index and of the number of PCNA+ cells along with an increase in
      apoptosis and an arrest in S phase. In previous reports we suggested that a 1000
      D serum fraction from mice bearing large tumors could be responsible for the
      induction of this dormant tumor stage. In this study tumor cells incubated in
      vitro with that serum factor mimicked the inhibition and cellular alterations
      observed in vivo in the secondary tumor inhibited by the second peak of CR.
      Moreover, the passive transfer of this factor by the intra-peritoneal (i.p.)
      route induced an in vivo inhibition of an i.p. tumor reproducing the image
      characteristic of the second peak of CR. This represents a direct proof that this
      serum factor can restrain tumor growth in vivo and that it is, most probably, the
      effector of the second peak of CR.

PMID- 10948339
TI  - Expression and prognostic value of the standard CD44 protein in pulmonary
      adenocarcinoma.
AB  - We examined immunohistochemically the expression of the standard form of CD44
      (CD44S) tissue specimens from 164 patients with pulmonary adenocarcinoma. Of the
      164 specimens, 79 (48%) expressed CD44S and the incidence of expression
      correlated with the tumor size. The prognosis for CD44S positive patients was
      poorer than that of CD44S negative patients. Our findings suggest that CD44S
      plays an important role in tumor progression and that CD44S expression is a
      useful prognostic marker for pulmonary adenocarcinomas.

PMID- 10948340
TI  - Modifying effect of tuna orbital oil rich in docosahexaenoic acid and vitamin D3
      on azoxymethane-induced colonic aberrant crypt foci in rats.
AB  - The modifying effect of dietary tuna (Thunnus thynnus orientalis) orbital oil
      rich in docosahexaenoic acid (DHA) and vitamin D3 (VD3) on the development of
      azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in
      male F344 rats. Animals were given three weekly subcutaneous injections of AOM
      (15 mg/kg body weight) to induce ACF. The rats were fed the experimental diet
      containing 5% tuna orbital oil (low fish oil), 23.5% tuna orbital oil (high fish
      oil), 5% corn oil (low corn oil) or 23.5% corn oil (high corn oil) for 5 weeks,
      starting 1 week before the first dose of AOM. Animals were sacrificed 2 weeks
      after the last AOM injection to count colonic ACF and assay the expression of
      cyclooxygenase (COX)-1 and -2. High corn oil diet significantly increased the
      development of ACF, when compared with low corn oil diet (P<0.005). High fish oil
      diet also increased ACF formation compared with low fish oil diet (P<0.01), but
      the increase was smaller than high corn oil diet. The frequency of ACF was
      significantly lower in the rats fed high fish oil diet than high corn oil diet
      (P<0.02). Moreover, frequency of ACF consisted of 4 or more crypts in rats fed
      the high fish oil diet was significantly lower than that of rats given high corn
      oil diet. COX-1 and COX-2 expression did not significantly differ among the
      groups. These results suggest that fish oil derived from tuna, which contains
      high amounts of DHA and VD3, suppresses the formation and growth of ACF without
      affecting COX-1 and COX-2 expression, and may have a preventive effect on colon
      carcinogenesis.

PMID- 10948341
TI  - P53 and radiotherapy for oesophageal carcinoma: A comparison between 4 different
      antibodies.
AB  - Wild-type p53 protein plays an important role in the cellular response to
      ionising radiation and other DNA damaging agents and is mutated in many human
      tumours. Immunohistochemistry is a rapid method to detect elevated protein
      levels. The p53 status in a group of patients treated by radiotherapy exclusively
      for oesophagus carcinoma was examined and correlated with pre-treatment
      parameters and treatment outcome with regard to overall survival, local
      recurrence-free survival and distant metastases-free survival. Four different
      antibodies were used to evaluate their predictive power to detect p53 expression.
      Immunostaining for p53 protein with 4 different antibodies was performed on
      paraffin-embedded specimens from 69 patients with adenocarcinoma and squamous
      cell carcinoma of the oesophagus. All patients were treated with radiotherapy
      exclusively, consisting of external irradiation combined with intraluminal
      brachytherapy. Detection of p53 using the antibody (DO7) was significantly
      correlated with overall survival and distant metastases-free survival. For local
      recurrence-free survival no statistical significance was reached. The use of the
      other 3 antibodies all showed the same trend with regard to distant metastases,
      however statistical significance was not reached. The use of multiple antibodies
      did not increase the predictive value of DO7. Both for survival and metastases
      free survival the use of DO7 alone was sufficient as a significant prognostic
      factor. We conclude that in this series, only the use of DO7 was correlated with
      prognosis in oesophagus carcinoma treated by radiotherapy only and that addition
      of 3 antibodies did not improve the predictive power.

PMID- 10948342
TI  - Angiogenesis in metastatic verrucous carcinoma of the uterine cervix.
AB  - A 65-year old woman operated on for verrucous carcinoma of the uterine cervix 13
      years previously was found to have multiple small recurrent tumors in the
      retroperitoneal space. Tumor cell expression of vascular endothelial growth
      factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) was
      investigated at the second operation. Expression of VEGF was strongly positive in
      the tumor cells and expression of PD-ECGF was strongly positive in both the tumor
      cells and the interstitial cells.

PMID- 10948343
TI  - Postoperative adjuvant chemotherapy with cisplatin, etoposide, and pirarubicin
      for endometrial carcinoma patients with lymph node metastasis: A pilot study.
AB  - We evaluated the effects of a combined chemotherapy regimen on endometrial
      carcinoma in 14 patients with lymph node metastasis. After surgery, the patients
      were treated with 3 cycles of chemotherapy (PVP regimen) every 4 weeks. The PVP
      regimen consisted of 75 mg/m2 cisplatin on day 1, 40 mg/m2 pirarubicin (P) on day
      1, and 75 mg/m2 etoposide (VP-16: V) on days 2, 3 and 4. The effect of adjuvant
      chemotherapy was evaluated based on progression-free survival (PFS), overall
      survival (OS), and adverse effects. The 5-year PFS rate was 52% [95% confidence
      interval (CI), 10-94%], and the 5-year OS rate was 50% (95% CI, 16-84%). The
      major toxicity was myelosuppression. One hundred percent of patients had
      neutropenia above grade 3, but all recovered from myelosuppression. PVP therapy
      may be an effective adjuvant therapy for endometrial carcinoma patients with
      lymph node metastasis used as an alternative to radiation therapy.

PMID- 10948344
TI  - Telomerase activity in gliomas with the use of non-radioisotopic and semi
      quantitative procedure for terminal repeat amplification protocol.
AB  - To study the role of telomerase in the pathogenesis of different grades and
      subtype of gliomas, telomerase activity in 31 gliomas was assessed with the use
      of non-radioisotopic and semi-quantitative procedures for the terminal repeat
      amplification protocol in this study. Among the samples were 17 glioblastoma
      multiformes (GBMs); 4 anaplastic astrocytomas (AAs); 5 astrocytomas (ASs); 1
      ependymoblastoma (EPB); 2 ependymomas (EPs); 1 oligodendroglioma (OG) and 1
      medulloblastoma (MB). Postive telomerase activity was detected in 9 of 17 GBMs
      (53%), 1 of 4 AAs (25%), 1 of 5 ASs (20%), 1 of 1 EPB (100%), and in positive
      controls, T 98G and KE-1. Weakly positive activity was detected in 2 of 3 AAs
      (66%) and 2 of 5 ASs (40%). No telomerase activity was detected in 8 of 17 GBMs
      (47%), 1 of 4 AAs (25%), 2 of 5 AS (40%), 2 of 2 (100%) EPs, 1 of 1 OG (100%), 1
      of 1 MB (100%) and normal brain tissue. We defined telomerase expression as
      positive and weakly positive cases. The percentage of telomerase activity
      expression in gliomas tended to correlate with tumour grade in spite of
      histopathology of tumours. These results indicated that the telomerase activity
      of gliomas may be used as a tumour marker and that the activation of telomerase
      should correlate with initiation and malignant progression of gliomas. In
      addition, non-radioisotopic and semi-quantitative procedure for the terminal
      repeat amplification protocol appears to be the most suitable to detect
      telomerase activity expression in small neurosurgical specimens.

PMID- 10948346
TI  - Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1
      to endometrial adenocarcinoma in vitro and in vivo.
AB  - Missile therapy, which destroys cancer cells specifically, has been regarded as
      an effective treatment modality for carcinoma. The monoclonal antibody MSN-1
      (IgM), which reacts strongly with endometrial adenocarcinomas, was combined with
      adriamycin (ADM) by a disulfide bond using N-succinimidyl-3-(2-pyridyldithio)
      propionate (SPDP) and 2-iminothiolane. Its selective cytotoxicity against SNG-II
      was examined in a colony formation in vitro, and on athymic mice in vivo. The
      results of our study suggest that the <inhibitory concentration> or IC50, of the
      MSN-1-ADM immunoconjugate against SNG-II to be 57 times that of ADM alone in
      vitro. The reductions in resected weights of target tumor cells, at the local
      site of the MSN-1-ADM immunoconjugate treatment, were 25% with caudal vein
      administration, and 38% with local administration, as compared with the untreated
      group, in vivo. There was no weight loss in treated mice. Our results suggest
      that this MSN-1-ADM immunoconjugate has potential clinical application in the
      treatment of endometrial adenocarcinomas.

PMID- 10948345
TI  - Antitumoral action of 2-deoxy-D-glucose tetraacetate in human melanoma cells.
AB  - The ester 2-deoxy-D-glucose tetraacetate (2-DOGTA) was recently shown to display
      cytostatic and cytotoxic activity in various lines of tumoral cells. In the
      present work, it was found to inhibit cell growth and confer chemosensitivity to
      cisplatin in two lines of human melanoma cells, poorly responsive to cisplatin.
      The inhibition of cell growth by 2-DOGTA was apparently not attributable to
      alteration of either D-glucose utilization or oxidation in these melanoma cell
      lines. In freshly isolated human melanoma cells, 2-DOGTA also inhibited cell
      growth, even in cells resistant to standard chemotherapeutic agents, such as
      temozolomide, cisplatin and/or vindesine. It is proposed, therefore, that 2-DOGTA
      should be further investigated for the treatment of melanoma patients, whether
      alone or in combination with known chemotherapeutic agents.

PMID- 10948348
TI  - Expression of Cu,Zn-SOD, Mn-SOD and GST-pi in oral cancer treated with
      preoperative radiation therapy.
AB  - Radical scavengers play an important role in cancer cells defending themselves
      against free radicals which occur with irradiation. SOD (Cu,Zn, Mn-) and GST-pi
      are radical scavengers with an effect on radiation therapy. We investigated the
      correlation between radiation effects and expression of Cu,Zn-, Mn-SOD and GST-pi
      in 34 cases of oral cancer, treated with preoperative radiation therapy. In this
      study, 22 cases out of 34 were classified as effective and 12 cases as non
      effective. Expression of Cu,Zn, Mn-SOD and GST-pi were observed in 13 (38.2%), 10
      (29.4%) and 20 (58.8%) cases, respectively. Regarding the value of radiation
      sensitivity from expression of these proteins in the biopsy samples, no
      significant correlation was found between those expressions and histological
      effectiveness of preoperative radiation therapy. But interestingly, in 11 out of
      12 of the non-effective cases, strong staining of Cu, Zn-SOD and GST-pi were
      shown at the residual cancer cells after preoperative radiation therapy. These
      results suggested that the expression of SOD (Cu,Zn-, and Mn-) and GST-pi may be
      not useful markers for predicting the effects of radiation therapy. However, Cu,
      Zn-SOD and GST-pi were increased by irradiation and may play an important role in
      radiation resistance and cancer cell regeneration after radiation therapy.

PMID- 10948347
TI  - Radiation therapy following mastectomy for axillary node-positive breast cancer:
      indication of chest wall irradiation.
AB  - This retrospective study was conducted to determine the indication of chest wall
      irradiation following mastectomy in axillary node-positive breast cancer
      patients. Between 1982 and 1993, 103 women with axillary node-positive breast
      cancer received postoperative radiation therapy following mastectomy using the
      hockey-stick field, which included the ipsilateral supraclavicular fossa and
      internal mammary nodes, without the chest wall. Ages ranged from 33 to 73 years
      (median: 47). Thirty-five patients underwent modified radical mastectomy, 48
      radical mastectomy, and 20 extended radical mastectomy. Twenty-two patients had 1
      3 positive axillary nodes, and 81 had 4 or more positive axillary nodes. The
      total doses ranged from 42 to 64 Gy (median 54 Gy) with a daily fraction size of
      2 Gy. Adjuvant chemotherapy was given to 75 patients, and hormone therapy was
      administered to 78 patients. The median follow-up time was 121 months (range, 68
      191 months) for the 57 surviving patients. The actuarial overall survival rate
      and the chest wall control rate at 10 years for all patients were 55% and 85%,
      respectively. Of the 103 patients, 14 developed chest wall recurrence. In the
      analysis, status of vascular invasion alone had a significant impact on chest
      wall control. In patients with definite vascular invasion, 2 of 5 (40%) patients
      with 1 to 3 positive axillary nodes, and 10 of 31 (32%) with 4 or more positive
      axillary nodes developed chest wall recurrence. In contrast, no patients without
      definite vascular invasion developed chest wall recurrence. Factors such as age,
      menopausal status, pathology, tumor location, extent of resection, estrogen
      receptor status, total dose, chemotherapy, and hormone therapy did not influence
      the development of chest wall recurrence. Among node-positive breast cancer
      patients following mastectomy, those with definite vascular invasion should be
      delivered chest wall irradiation regardless of the number of positive axillary
      nodes. In contrast, those without definite vascular invasion need not be
      administered chest wall irradiation.

PMID- 10948349
TI  - Molecular detection of microsatellite instability in basal cell carcinoma.
AB  - Several studies have shown that the presence of genetic instability can be
      associated to carcinogenesis process. The detection of microsatellite instability
      (MI) that consists of an expansion and/or deletion of DNA within repeat
      sequences, may constitute a sensitive marker for the presence of gene mutations.
      A series of 18 basal cell carcinoma (BCC) consecutive patients was examined for
      the presence of alteration in 12 DNA microsatellite markers, in order to better
      understand the molecular significance of MI in the genesis and progression of
      BCC. Molecular alterations were detected in 6 out of 12 analyzed microsatellite
      loci. Five out of 18 BCC samples showed loss of heterozygosity at chromosome loci
      localized in the vicinity of the tumor suppressor genes, whereas six out of 18
      BCC patients presented at least one altered microsatellite (instability). We
      demonstrated molecular genetic alterations at 2p16 locus, in the proximity of
      MSH2 <mismatch repair> gene and 17p21, in the proximity of the p53 gene. These
      data validate and confirm a role of MI in genesis and progression of BCC, by
      analysis of markers localized at specific chromosome region in proximity of
      oncogenes and tumor suppressor genes.

PMID- 10948350
TI  - Evidence for in the appearance of mRNAs of nucleotide excision repair genes, in
      human ovarian cancer tissues.
AB  - Nucleotide excision repair (NER) is the DNA repair pathway through which
      cisplatin-DNA intrastrand adduct is repaired. Clinical studies have shown that
      increased mRNA expression of selected genes involved in the rate-limiting step of
      NER, appear to be closely associated with clinical resistance to platinum agents.
      These specific studies have led to the possibility of an assessment of the order
      in which, the appearance of mRNAs of selected NER genes may occur. Included in
      this assessment are ERCC1, XPB, CSB, and XPA, studied in 28 ovarian cancer tumor
      tissue specimens. The study of these four genes, in pairs, from 28 ovarian cancer
      specimens, results in 168 separate observations. Based on the mRNA expression
      patterns of these genes in these tissues, it is suggested that ERCC1 mRNA may
      appear before the mRNA of any of the other genes, in an obligate fashion. This is
      followed by XPB mRNA; which appears before the mRNA of XPA; which in turn, may
      appear before CSB. This pattern is consistent with what we have reported
      previously, in non-malignant human bone marrow specimens from a cohort of 52
      patients.

PMID- 10948351
TI  - Local and systemic control for osteosarcoma of the extremity treated with
      neoadjuvant chemotherapy and limb salvage surgery: the Rizzoli experience.
AB  - Five-hundred and twenty-six patients with non-metastatic osteosarcoma of the
      extremities treated at Istituto Ortopedico Rizzoli from 1983 to 1995 with
      neoadjuvant chemotherapy and limb salvage, were retrospectively studied to
      evaluate the rate of local and systemic control. At a mean follow-up of 9.5 years
      (3-17), 320 patients remained continuously free of disease and 206 relapsed. The
      5-year disease-free survival and overall survival were 64% and 70% respectively.
      In patients who relapsed, there were 31 local recurrences (6%). The rate of local
      failures was significantly higher in the 79 patients with inadequate surgical
      margins (marginal, intralesional, and contaminated margins) than in the 486
      patients with wide surgical margins (2.6% vs. 25.0%; P<0.0001). Twenty-nine of
      the 31 patients (94%) with local recurrence also had metastases and died of the
      tumor. In comparison with patients who only had a systemic relapse, patients with
      local recurrences had a higher rate of metastases located in bones (41% vs. 7%;
      P<0.001), and a worse post-relapse outcome (5-year overall survival: 6% vs. 24%;
      P<0.04). We concluded that in osteosarcoma of the extremity treated with
      neoadjuvant chemotherapy: i) limb salvages procedures do not compromise the
      outcome of patients, provided the achievement of adequate surgical margins; ii)
      local recurrences are a marker either of the inadequacy of local treatment or of
      the high local and systemic aggressiveness of the tumor.

PMID- 10948352
TI  - Weekly CODE chemotherapy with recombinant human granulocyte colony-stimulating
      factor for relapsed or refractory small cell lung cancer.
AB  - We used cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) weekly for
      salvage chemotherapy in relapsed or refractory small cell lung cancer (SCLC). We
      reviewed the medical charts of patients between January 1993 and December 1996 at
      the National Nishi-Gunma Hospital. Twenty patients were treated with salvage
      chemotherapy. The overall response rate was 55.0%. The median survival time of
      extensive disease patients from the start of CODE therapy was 23 weeks and the 1
      year survival rate was 21.0%. Toxicities were severe, especially in
      myelosuppression. CODE could be selected as a salvage therapy for chemotherapy-
      relapsed SCLC cases.

PMID- 10948353
TI  - Low apoptotic activity in primary prostate carcinomas without response to
      hormonal therapy.
AB  - Proliferative and apoptotic activities, as well as p53 protein expression, of ten
      untreated primary prostate carcinomas that showed extremely poor response to
      hormonal therapy (primary androgen independent prostate carcinomas) were compared
      with the stage- and grade-matched primary tumor specimens with favorable response
      to hormonal therapy (androgen dependent prostate carcinomas). The mean
      proliferative activity measured by Ki-67 immunohistochemistry was slightly higher
      in the primary androgen independent prostate carcinomas (8.70+/-5.24) than in the
      androgen dependent prostate carcinomas (7.09+/-2.68; p=0.27). The mean apoptotic
      activity by in situ end-labeling technique in the primary androgen independent
      prostate carcinomas (0.96+/-1.03) was less than half of that in the androgen
      dependent prostate carcinomas (2.75+/-0.98; p=0.0001). Ten percent of the
      androgen dependent prostate tumors showed p53 protein expression, whereas 30% of
      the primary androgen independent prostate tumors were immunopositive for p53
      (p=0.30). In summary, we have shown that apoptotic activity in the primary
      androgen independent prostate carcinomas is significantly lower than in the
      matched androgen dependent prostate carcinomas while the proliferative activity
      remains unaffected. These results suggest that primary androgen independent
      prostate carcinomas may have genetic properties, such as inactivation of the p53
      gene, that enable them to escape apoptosis caused by androgen ablation.

PMID- 10948354
TI  - Transplacental effects of a 15% olive-oil diet on chemically-induced
      tumorigenesis in offspring.
AB  - We evaluated whether feeding pregnant female rats a diet high in olive-oil, that
      showed a tumor-preventive effect in adults, has a similar preventive effect on
      chemically-induced cancer in offspring (i.e. mammary glands and colon cancer in
      rats). The control group was fed the same 7% corn-oil diet as their mothers.
      Experimental group I was fed a 7% corn-oil diet while their mothers received a
      15% olive-oil diet. Experimental group II was fed the same 15% olive-oil diet as
      their mothers. Female offspring were twice administered 7,12
      dimethylbenz(a)antracene (DMBA) in doses of 10 mg/rat. Male offspring were
      injected 6 times with 1, 2-dimethylhydrazine (DMH) in doses of 20 mg/kg body
      weight. Effect of DMBA was manifested in a high rate of tumorigenesis: the number
      of tumor-bearing rats in control offspring reached 52.0%. This effect increased
      to 60.6% among offspring of experimental group II and to 67.7% in offspring of
      experimental group I. The mean tumor size increased significantly in control
      offspring. Following administration of DMH number of tumor-bearing rats was
      similar in all groups of offspring: 36.7%, 40.7% and 42.8%. Tumor types differed:
      the majority of tumors in the control group were benign polyps and adenomas
      (72.1%) and the number of adenocarcinomas was low (27.9%). The number of
      malignant tumors increased to 37.5% in offspring of experimental group II and to
      45.5% in offspring of experimental group I. In control group offspring, a
      distinct tendency to increased body weight and a significant increase in spleen
      weight were seen. The findings indicate that feeding mothers a diet high in fat
      concentrations, even those with known tumor preventive significance in adults,
      lose this cancer-inhibiting role in offspring.

PMID- 10948355
TI  - Gene reorganisations and expression of c-ras, c-src, c-mos and c-fos oncogenes in
      Namalwa, Wish and C6 cells.
AB  - In a wide variety of neoplasms, proto-oncogenes were found transcriptionally
      activated by different DNA rearrangements. In the present study we used Namalwa,
      Wish and C6 cell lines in order to investigate the correlation between gene
      reorganisations and their expression. According to Southern and fluorescence in
      situ hybridisation (FISH) analysis the oncogenes c-ras, c-src and c-fos were
      amplified in Namalwa and Wish cells. reorganisation other than amplification was
      found for c-mos in the three cell cultures investigated. The amplification levels
      of the genes studied were assessed by dot blot hybridisation followed by
      densitometric scanning. c-H-ras and c-src were amplified about 20-fold in the
      genomes of Namalwa and Wish, while c-fos was amplified approximately 12-fold in
      the same cell lines. The hybridisation signals in C6 were almost the same as in
      the control lymphocytes for the four oncogenes investigated. Similar results were
      obtained for c-mos in the genomes of all cell lines examined. Using RT-PCR,
      overexpression of proto-oncogenes c-ras, c-src, c-mos and c-fos was found in
      Namalwa and Wish cells. In C6 cells the expression of the four genes studied was
      marginal. Overexpression of c-mos was observed in Namalwa and Wish cells, while
      in C6 it was marginal although existence of reorganisation was found. Hence, it
      might be suggested that in C6 cells c-mos is down-regulated from other factors
      and/or genes, or requires for its activation overexpression of other genes.

PMID- 10948357
TI  - Science is under increasing public scrutiny.

PMID- 10948356
TI  - Protein-bound polysaccharide increases survival in resected gastric cancer cases
      stratified with a preoperative granulocyte and lymphocyte count.
AB  - A multicenter comparative trial of mitomycin C and futraful (MMC+FT), with or
      without protein-bound polysaccharide (PSK), was carried out by the Study Group
      for Surgical Adjuvant Chemotherapy for Gastric Cancer from 1978 to 1981. In 751
      patients who underwent macroscopically curative resection preoperative
      granulocyte and lymphocyte count ratios (G/L) were measured. These patients were
      stratified with a preoperative cut-off of G/L:2.0, and those with or without PSK
      were compared in terms of survival rates. In the overall (non-stratified) series,
      the 5-year survival rate of the PSK group was 67.9%, while that of the non-PSK
      group was 61.8% (p=0.053). In the group with a preoperative G/L ratio of >/=2.0,
      the 5-year survival rate of the PSK group (n=182) was 68.7%, while that of the
      non-PSK group (n=182) was 55.4% (p=0.007). In the cases with a preoperative G/L
      ratio of <2.0, there was no significant difference in the survival rates: 67.1%
      in the PSK group (n=195) and 67.8% in the non-PSK group (n=192). It was found
      that PSK extended survival in the group of patients with a preoperative G/L ratio
      of >/=2.0, perhaps through restoration of immunocompetence.

PMID- 10948358
TI  - The character or the variation: the genetic analysis of the insecticide
      resistance phenotype.
AB  - In this critique it is argued that the genetic basis of the evolution of
      resistance is dependent on how the phenotypic, and underlying genotypic,
      variation is channelled during a selective response. A polygenic response is
      preferentially favoured if selection acts within the phenotypic distribution of
      susceptibles; a monogenic response is predicted if selection screens rare
      mutations with phenotypes outside that susceptible distribution. The relevance of
      this model to the method of genetic analysis, the prediction of resistance
      mechanisms to novel insecticides, the generation of resistant beneficial insects
      and the development of the most effective resistance and integrated pest
      management programmes is discussed.

PMID- 10948359
TI  - Prospects for the biological control of subterranean termites (Isoptera:
      rhinotermitidae), with special reference to Coptotermes formosanus.
AB  - Costs associated with subterranean termite damage and control are estimated to
      approach $2 billion annually in the United States alone. The Formosan
      subterranean termite, Coptotermes formosanus Shiraki, is one of the more
      economically important subterranean species. In recent years, the shortcomings
      associated with conventional chemical control methods have prompted policymakers
      and scientists to evaluate the potential for biological control of subterranean
      termites (C. formosanus in particular), that is, to determine the potential for
      natural enemies - predators, parasitoids and pathogens - to suppress termite
      populations. Ants are the greatest predators of termites, and may have a
      considerable local impact on termite populations in some areas of the world. A
      few parasitoids of termites are known, but their potential for regulating termite
      populations seems negligible. Characteristics of the colony, such as a protected,
      underground location (and, for the C. formosanus nest, its modular and dispersed
      nature), are likely to limit the impact predators and parasitoids have on
      subterranean termites. Thus, there seems little potential for use of these agents
      for subterranean termite control. For various reasons, pathogenic organisms, such
      as viruses, bacteria, Protozoa, nematodes and most fungi, have shown little
      promise for use in biological termite control. However, research suggests that
      strains of two well-studied, endoparasitic fungi, Beauveria bassiana and
      Metarhizium anisopliae, when employed in baiting schemes, may offer the potential
      for at least some measure of subterranean termite control, although their
      successful use is compromised by a number of inherent biological limitations and
      logistical problems that have yet to be solved. Although not strictly in the
      realm of classical biological control, recent studies suggest that natural
      products, such as ant semiochemicals and fungal metabolites (siderophores), or
      their synthetic analogues, eventually might find a use in termite control
      programmes as repellents or insecticides in wood treatments or soil applications
      if stable formulations can be developed.

PMID- 10948360
TI  - Geographical origin of an introduced pest species, Delia radicum (Diptera:
      anthomyiidae), determined by RAPD analysis and egg micromorphology.
AB  - The origin of introduction of the cabbage root fly, Delia radicum Linnaeus to the
      north-eastern coast of North America in the 19th century has been assumed to be
      from Europe. From that point of introduction, D. radicum gradually spread
      westward to occupy available ecological niches. DNA fingerprinting and egg
      micromorphology were used to determine the most likely geographical origin of the
      North American populations of this species. Forty-five informative RAPD loci
      obtained from ten primers and three criteria for egg micromorphology were
      studied. These characters indicated a common origin for the North American
      populations and a high similarity between populations from North America and
      north-western Europe. The results suggest a single entrance point of D. radicum
      into North America, probably via the north-eastern coast (New York area) from
      north-western Europe. The implications of this study in assisting selection of
      natural enemies of this important agricultural pest are discussed.

PMID- 10948361
TI  - Clones of pea aphid, Acyrthosiphon pisum (Hemiptera: aphididae) distinguished
      using genetic markers, differ in their damaging effect on a resistant alfalfa
      cultivar.
AB  - CUF 101, a resistant cultivar of alfalfa, was exposed to 15 clones of
      Acyrthosiphon pisum Harris collected from alfalfa fields in three regions of
      France (east, south, central west) to determine whether the level of resistance
      varied across the different clones. The survival of alfalfa seedlings infested at
      the cotyledon stage was assessed using a standardized method. Although no
      difference in seedling mortality was detected between clones grouped by region,
      there was a significant variation among the 15 pea aphid clones. In particular,
      two clones of southern origin were more aggressive. In addition, the different
      pea aphid clones were characterized using allozyme and RAPD-PCR markers. Among
      the 15 clones, seven allozyme genotypes (plus one when adding colour
      polymorphism) and 12 RAPD-PCR genotypes were distinguished. The two southern
      clones differing by their aggressiveness on the resistant alfalfa belonged to the
      same allozyme and RAPD genotype which was distinct from the other pea aphid
      clones. Our results reinforce the need to take into account aphid genetic
      diversity in breeding programmes for resistance in cultivated plants.

PMID- 10948362
TI  - Domesticity of Lutzomyia whitmani (Diptera: psychodidae) populations: field
      experiments indicate behavioural differences.
AB  - The sandfly Lutzomyia whitmani (Antunes & Coutinho) is an important vector for
      cutaneous leishmaniasis throughout much of Brazil, and has recently been shown to
      consist of more than one mitochondrial lineage. It has frequently been asserted
      that the degree of adaptation of L. whitmani to human environments varies across
      its range. As a standardized test of indoor feeding for three geographically
      distant populations of L. whitmani, catches inside experimental chicken sheds of
      varying degrees of wall closure (0%, 33%, 67% and 98%) were compared. Each
      increment in shed closure reduced catches of females (relative to the most open
      shed) by a similar degree for each population: geometric mean catches dropped by
      11-40% with 33% closure, by 41-62% with 67% closure, and by 69-100% with 98%
      closure. Geometric mean catches of males from the two more northerly populations
      also decreased with increasing shed closure, by 18% and 22% for 33% closure, 58%
      and 69% for 67% closure, 91% and 93% for 98% closure. Males from the most
      southerly population showed significantly different behaviour, with 33% closure
      causing a 54% increase in geometric mean catch, 67% closure causing a 6%
      increase, and 98% closure causing a 32% reduction. For this southerly population,
      sex ratios became more male biased with increasing density in more closed sheds,
      suggesting aggregation driven by intra-specific communication. Lutzomyia
      intermedia (Lutz & Neiva) was relatively more likely than L. whitmani to approach
      baits in the three more closed sheds, rather than the most open shed, offering a
      behavioural explanation for observed differences in indoor biting rates between
      the species.

PMID- 10948363
TI  - Tethered flight activity of Nephotettix virescens (Hemiptera: cicadellidae) in
      the Philippines.
AB  - The flight potential of Nephotettix virescens (Distant), the most important
      vector of rice tungro virus disease, was assessed using tethered flight
      techniques. Most individuals tested were not willing to fly in response to
      stimulation, or flew for very short times. A small proportion of leafhoppers flew
      for long periods and one female flew for almost 7 h, indicating the potential for
      long distance dispersal of insects and inoculum. Few individuals flew before four
      days of age and thereafter flight profiles were similar for insects aged between
      four and 12 days. Mature females were more flight willing when kept as adults in
      mixed groups with males than when caged separately. There was no consistent
      effect on flight performance when insects were reared on rice varieties with
      different levels of leafhopper resistance. The flight activity of N. virescens
      was greater when leafhoppers were reared on mature, compared with young, rice
      plants. Leafhoppers reared through one generation on tungro-diseased rice plants
      were less willing to fly than individuals maintained on healthy plants of the
      same age and variety, whereas those tested after a 24-h access period to tungro
      diseased plants were more flight-willing. The results are discussed in relation
      to the spread of tungro and to management interventions for the control of the
      disease.

PMID- 10948364
TI  - Host choice and host leaving in Rhopalosiphum padi (Hemiptera: aphididae)
      emigrants and repellency of aphid colonies on the winter host.
AB  - Host choice and winter-host leaving in emigrants of bird cherry-oat aphid,
      Rhopalosiphum padi (Linnaeus), were investigated in the laboratory. In settling
      choice tests, emigrants collected from the winter host, Prunus padus, preferred
      this plant over a summer host, oats. Emigrants which had left P. padus for up to
      24 h did not express a preference as a group, and those which had left for 24-48
      h preferred oats. Eighty seven percent of emigrants caged as fourth-instar nymphs
      on P. padus leaves abandoned the host by the second day of adult life, and
      apparently did not subsequently return to the leaf. In an olfactometer, P. padus
      leaves which had supported spring generations of R. padi were repellent to
      emigrants. Volatiles were entrained from uninfested and R. padi-infested P. padus
      using cut twigs in the laboratory as well as intact twigs on a tree in the field.
      Entrainment extracts from uninfested P. padus had no effect on emigrants in the
      olfactometer, whereas those from twigs infested with nymphal emigrants were
      repellent. The study indicates that in R. padi, host-alternation is driven by
      behavioural changes which occur in individuals as well as between morphs.

PMID- 10948365
TI  - A polymerase chain reaction based method for the detection of Culex
      quinquefasciatus (Diptera: culicidae).
AB  - Culex quinquefasciatus Say is the major vector of the filarial parasite
      Wuchereria bancrofti (Cobbold) which causes lymphatic filariasis in humans. A
      repetitive DNA sequence from the genome of C. quinquefasciatus has been cloned
      and completely sequenced. The 693 bp cloned fragment had an A+T content of 72%.
      Dot matrix analysis of the fragment did not reveal any direct or inverted repeats
      within it. Southern blot analysis using a variety of restriction enzymes appeared
      to indicate that the cloned fragment was interspersed within the genome with a
      copy number of approximately 30,000. A search of the GenBank database did not
      reveal significant homologies to any previously cloned sequences. Although the
      probe was sensitive enough to detect picogram quantities of DNA, it was not
      specific for C. quinquefasciatus, as it hybridized with DNA from other mosquito
      species, Culex pseudovishnui Colless, Culex gelidus Theobald, Culex
      tritaeniorhynchus Giles, Anopheles vagus Donitz and Mansonia uniformis
      (Theobald). However PCR primers derived from the cloned sequence, IpC, were found
      to be specific and amplified only C. quinquefasciatus DNA. The optimized PCR
      assay was found to be very sensitive and was capable of detecting DNA from all
      stages of C. quinquefasciatus thus making it an ideal diagnostic tool.

PMID- 10948366
TI  - Influence of egg load and oviposition time interval on the host discrimination
      and offspring survival of Anagyrus pseudococci (Hymenoptera: encyrtidae), a
      solitary endoparasitoid of citrus mealybug, ++Planococcus citri (Hemiptera:
      pseudococcidae).
AB  - Oviposition and host discrimination behaviour of unmated Anagyrus pseudococci
      (Girault), an endoparasitoid of the citrus mealybug Planococcus citri (Risso),
      were investigated in the laboratory. Female parasitoids were able to discriminate
      between parasitized hosts and healthy ones. The mean number of ovipositions was
      significantly higher in unparasitized than in parasitized hosts. Conspecific
      superparasitism occurred more often than self-superparasitism. Changes in
      consecutive ovipositions over three hours by A. pseudococci suggested that egg
      load influenced the discrimination behaviour of the parasitoids, with females
      which had low egg loads mostly avoiding oviposition in already parasitized hosts
      at time intervals ranging from 0 h to 96 h, and distributing their eggs in the
      high quality (unparasitized) hosts. The parasitized hosts were rejected more
      commonly through antennal perception of external markers than during ovipositor
      probing which could have encountered internal markers but this relationship
      changed with increasing time after oviposition. The parasitoid's oviposition rate
      in unparasitized and conspecific-parasitized hosts varied at the different
      oviposition time intervals when the females had fewer eggs in the ovaries.
      Percentage emergence of parasitized offspring was not significantly influenced by
      whether they developed in single or superparasitized mealybugs. The significance
      of host discrimination by A. pseudococci is discussed.

PMID- 10948367
TI  - Attraction of apple maggot flies, Rhagoletis pomonella (Diptera: tephritidae) of
      different physiological states to odour-baited traps in the presence and absence
      of food.
AB  - Adults of apple maggot fly Rhagoletis pomonella (Walsh) of differing
      physiological states were marked and released in blocks of apple trees ringed by
      sticky red spheres. Spheres were either unbaited, baited with butyl hexanoate
      (synthetic host fruit odour) or baited with both butyl hexanoate and ammonium
      carbonate (synthetic food odour). All trap and lure treatments were compared in
      the presence or absence of food (bird faeces) in the blocks. Simultaneously, the
      response of wild immigrant flies to treatments was measured and wild females were
      dissected to determine state of ovary development. Large proportions (25-40%) of
      released mature male and female R. pomonella were recovered in blocks having
      traps baited with butyl hexanoate. Ammonium carbonate did not enhance trap
      captures and presence of food had little effect on response to synthetic odours
      by mature R. pomonella. Immature flies of each sex responded weakly to traps and
      to both types of synthetic lures and may have been arrested in blocks having
      food. Wild flies of both sexes exhibited a response pattern very similar to
      mature released flies, regardless of eggload (in the case of wild females).
      Results indicate that wild R. pomonella immigrating into apple orchards are
      primarily mature, and not hungry for protein. Behavioural control strategies are
      discussed in that context.

PMID- 10948368
TI  - Diapause termination in the millet stem borer, Coniesta ignefusalis (Lepidoptera:
      pyralidae) in Ghana as affected by photoperiod and moisture.
AB  - Studies were conducted in northern Ghana in 1997 and 1998 on the effects of
      contact moisture and photoperiod on the termination of larval diapause in the
      stem borer, Coniesta ignefusalis (Hampson). Results obtained over the two years
      consistently showed that on its own, photoperiod had no significant effect on
      diapause termination. In combination with contact moisture, however, a long day
      photoperiod of 13L:11D accelerated diapause termination and increased the
      cumulative percentage pupation. Contact with moisture was crucial for diapause
      termination but its influence was more pronounced in larvae collected from the
      field after March. Generally, access to moisture earlier than April resulted in
      very high larval mortality. These observations, together with the fact that some
      of the larvae (12%) denied access to water throughout the experimental period
      subsequently pupated, suggest that moisture may not be the sole factor triggering
      diapause termination in C. ignefusalis. The implications of these findings are
      discussed.

PMID- 10948369
TI  - Mating interactions between two biotypes of the whitefly, Bemisia tabaci
      (Hemiptera: Aleyrodidae) in Australia.
AB  - The biological consequences of mating interactions between indigenous and exotic
      biotypes of Bemisia tabaci (Gennadius) in Australia were studied using a
      combination of field and laboratory experiments. The key results of the
      interaction between the B and eastern Australian biotypes were reduced population
      increase, a marked increase in the proportion of male progeny, fewer eggs
      produced by females paired with males of different biotype and no difference in
      the numbers of eggs per unmated female and females paired with males of the same
      biotype. In addition, there was no change in the proportion of eggs hatching,
      mixed biotype pairs spent more time courting than single biotype pairs and a low
      level of hybridization in field cages and small containers was observed. These
      observations suggest three possibilities. The first is the 'distracting male
      hypothesis' in which mating pairs made up of different biotypes apportion more
      time to courtship and less time to egg laying than single biotype pairs. The
      second invokes the 'single-locus complementary sex determination model' in which
      the production of non-viable diploid male zygotes may explain the reduction in
      eggs laid. The third is cytoplasmic incompatibility between biotypes caused by
      Wolbachia. The results also suggest that the geographical distribution of
      clusters of related biotypes both overseas and in Australia may be explained by
      between-biotype interactions leading to the formation of parapatric populations.

PMID- 10948370
TI  - The potential of Lagenaria rootstock to confer resistance to the carmine spider
      mite, Tetranychus cinnabarinus (Acari: Tetranychidae) in Cucurbitaceae.
AB  - Antibiosis and resistance of six Cucurbita and two Lagenaria accessions to the
      carmine spider mite, Tetranychus cinnabarinus Boisduval, were evaluated in the
      laboratory. Significant differences among accessions were observed three days
      after the inoculation of detached leaf discs. The Lagenaria accessions, Slawi and
      Sus, proved to be the most resistant to mites, with average populations of mite
      eggs, 87 and 95%, respectively less than that of the susceptible C. pepo
      accession, Orangetti. The Cucurbita accessions, Tace, Brava, Tetsukabuto, Phoenix
      and TZ-148 had mite egg totals 4, 9, 13, 26 and 40%, respectively, less than
      those of accession Orangetti. The Sus accession of Lagenaria was resistant to T.
      cinnabarinus from the four-leaf stage until fruit set in laboratory and field
      tests. Grafting the susceptible Brava onto Sus rootstock increased the resistance
      of the scion to the same level as that of non-grafted Sus. Grafting the
      susceptible Cucumis melo Noy Yizre'el on resistant or susceptible rootstocks of
      Cucurbita and Lagenaria accessions did not affect its susceptibility to T.
      cinnabarinus. The results indicate that resistance to T. cinnabarinus can be
      transferred by grafting from Lagenaria stocks to Cucurbita scions but not in the
      opposite direction.

PMID- 10948371
TI  - Comparison of two alpha-cyano pyrethroids when impregnated into bednets against a
      pyrethroid resistant and susceptible strain of Anopheles stephensi (Diptera:
      Culicidae) and their F1 progeny.
AB  - The two alpha-cyano pyrethroid insecticides lambda-cyhalothrin and alpha
      cypermethrin were tested as bednet treatments at a target dose of 20 mg m-2. To
      establish their efficacy, female pyrethroid resistant and susceptible Anopheles
      stephensi Liston, and the F1-hybrids were allowed to fly freely in a room with a
      human subject under an impregnated net. Both treatments provided good personal
      protection by significantly reducing the number of blood fed mosquitoes compared
      to an untreated control net. Mortality after 24 h was significantly higher for
      the alpha-cypermethrin treated net when compared to lambda-cyhalothrin. For each
      insecticide there were no significant differences in the proportion of
      susceptible homozygotes and F1-hybrids found dead after a 24 h holding period,
      which suggests that there would be no selection for pyrethroid resistant
      heterozygotes by either of the insecticides.

PMID- 10948373
TI  - Long range forecasts of the numbers of Helicoverpa punctigera and H. armigera
      (Lepidoptera: Noctuidae) in Australia using the southern oscillation index and
      the sea surface temperature.
AB  - The use of long-term forecasts of pest pressure is central to better pest
      management. We relate the Southern Oscillation Index (SOI) and the Sea Surface
      Temperature (SST) to long-term light-trap catches of the two key moth pests of
      Australian agriculture, Helicoverpa punctigera (Wallengren) and H. armigera
      (Hubner), at Narrabri, New South Wales over 11 years, and for H. punctigera only
      at Turretfield, South Australia over 22 years. At Narrabri, the size of the first
      spring generation of both species was significantly correlated with the SOI in
      certain months, sometimes up to 15 months before the date of trapping.
      Differences in the SOI and SST between significant months were used to build
      composite variables in multiple regressions which gave fitted values of the trap
      catches to less than 25% of the observed values. The regressions suggested that
      useful forecasts of both species could be made 6-15 months ahead. The influence
      of the two weather variables on trap catches of H. punctigera at Turretfield were
      not as strong as at Narrabri, probably because the SOI was not as strongly
      related to rainfall in southern Australia as it is in eastern Australia. The best
      fits were again given by multiple regressions with SOI plus SST variables, to
      within 40% of the observed values. The reliability of both variables as
      predictors of moth numbers may be limited by the lack of stability in the SOI
      rainfall correlation over the historical record. As no other data set is
      available to test the regressions, they can only be tested by future use. The use
      of long-term forecasts in pest management is discussed, and preliminary analyses
      of other long sets of insect numbers suggest that the Southern Oscillation Index
      may be a useful predictor of insect numbers in other parts of the world.

PMID- 10948372
TI  - Experimental and molecular genetic analysis of the impact of pyrethroid and non
      pyrethroid insecticide impregnated bednets for mosquito control in an area of
      pyrethroid resistance.
AB  - Experimental huts in Cote d'Ivoire were used to evaluate the pyrethroid alpha
      cypermethrin, the non-ester pyrethroid etofenprox, the organophosphate pirimiphos
      methyl and the carbamate carbosulfan on bednets against pyrethroid-resistant
      Anopheles gambiae Giles. To test for selection for the resistance gene by the
      treated nets, A. gambiae collected live or dead from the huts were kept and
      analysed for the presence of the kdr gene using a new polymerase chain reaction
      followed by sequence-specific oligonucleotide probing (PCR-SSOP) for kdr
      genotyping. Deliberately holed bednets freshly treated with pirimiphos-methyl or
      carbosulfan caused over 90% kill of A. gambiae s.s. and Culex spp. However, the
      mortality with alpha-cypermethrin or etofenprox treated nets was similar to that
      with untreated nets. Bloodfeeding of A. gambiae s.s. on the sleepers under the
      nets was only significantly reduced by alpha-cypermethrin and carbosulfan. Tests
      of the residual activity of the bednets after seven months showed that pirimiphos
      methyl had lost its efficacy while carbosulfan still performed well. Once again
      the pyrethroid treated nets gave similar results to the untreated nets. Selection
      for the kdr-allele by alpha-cypermethrin and etofenprox, but not by carbosulfan,
      was indicated by PCR-SSOP genotyping of mosquitoes. Thus carbamates such as
      carbosulfan, or organophosphates of longer persistence than pirimiphos-methyl and
      of low mammalian toxicity, would seem to be a promising alternative to be used on
      bednets, particularly in areas of pyrethroid resistance.

PMID- 10948374
TI  - Sex pheromones of Callosobruchus subinnotatus and C. maculatus (Coleoptera:
      Bruchidae): congeneric responses and role of air movement.
AB  - Females of Callosobruchus spp. are known to produce sex pheromones that attract
      males. These sex pheromones cannot be adopted for use in pest management without
      first investigating the responses of the males in the windless conditions of
      storage environments. Consequently, behavioural bioassays of Callosobruchus
      subinnotatus Pic males were conducted in an olfactometer in the absence of air
      flow. Under these conditions males were found to be able to follow odour trails
      to the source. However, the latency period was longer in diffusional bioassays
      than for insects in a Y-tube olfactometer that provided directional wind cues.
      The highest percentage of males reached the pheromone source when components of
      the pheromones, (E)-3-methyl-2-heptenoic acid (E32A) and (Z)-3-methyl-2-heptenoic
      acid (Z32A), were formulated in a 50:50 or 25:75 ratio. Males of C. maculatus
      (Fabricius) responded to sex pheromone of C. subinnotatus, but males of C.
      subinnotatus did not respond to that of C. maculatus. The two sex pheromone
      components of C. subinnotatus are also constituents of C. maculatus sex
      pheromone. These two components may be potentially useful in monitoring the
      populations of both species in stored beans. It is postulated that (Z)-3-methyl-3
      heptenoic acid (Z33A), the major component of the sex pheromone of C. maculatus,
      must have acted as an antagonist inhibiting response of C. subinnotatus to the
      sex pheromone of C. maculatus.

PMID- 10948375
TI  - The response of Culex quinquefasciatus (Diptera: culicidae) to traps baited with
      carbon dioxide, 1-octen-3-ol, acetone, butyric acid and human foot odour in
      Tanzania.
AB  - The responses of Culex quinquefasciatus Say to traps baited with carbon dioxide,
      1-octen-3-ol, acetone, butyric acid and human foot odour were studied in the
      field in Muheza, north-east Tanzania using Counterflow Geometry (CFG) and Centers
      for Disease Control (CDC) traps. It was found that significantly more C.
      quinquefasciatus responded to foot odour collected on nylon stockings than to
      clean nylon stockings (P < 0.05). Significantly more mosquitoes were caught in a
      CFG trap baited with carbon dioxide than in traps with either human foot odour,
      acetone or butyric acid. It was also found that in an outdoor situation a carbon
      dioxide baited CDC unlit trap collected over 12 times more C. quinquefasciatus
      than an unbaited CDC unlit trap and nine times more mosquitoes than CDC traps
      baited with 1-octen-3-ol alone (P < 0.05). The number of mosquitoes caught in a
      CDC trap baited with 1-octen-3-ol did not differ significantly from that of the
      unbaited CDC trap (P > 0.05). These results indicate that the Afrotropical C.
      quinquefasciatus respond significantly better to traps baited with carbon dioxide
      than to either octenol, acetone or butyric acid, and that human foot odour
      contains stimuli to which C. quinquefasciatus is attracted under field
      conditions.

PMID- 10948376
TI  - Variation in tomato host response to Bemisia tabaci (Hemiptera: Aleyrodidae) in
      relation to acyl sugar content and presence of the nematode and potato aphid
      resistance gene Mi.
AB  - Two commercial cultivars of tomato, Alta and Peto 95, the accession line number
      LA716 of Lycopersicon pennellii and lines 94GH-006 and 94GH-033 (backcrosses
      between Peto 95 and LA716), with different leaf acyl sugar contents were screened
      for resistance to Bemisia argentifolii Bellows & Perring (corresponding to the
      Spanish B-biotype of Bemisia tabaci (Gennadius)), in greenhouse- and field-no
      choice experiments. There was no oviposition on LA716 (with the highest acyl
      sugar content) while the greatest fecundity and fertility values were observed on
      the cultivar Alta (no acyl sugar content). However, no clear relationship was
      found between the low acyl sugar content in the other tomato cultivars tested and
      whitefly reproduction. Thus, resistance to B. tabaci did not appear to correlate
      with acyl sugar content below a threshold level of 37.8 microg cm-2 leaf. In a
      greenhouse choice-assay, B. tabaci exhibited reduced host preference and
      reproduction on the commercial tomato cultivars Motelle, VFN8 and Ronita all of
      which carry the Mi gene resistance to Meloidogyne nematodes and the aphid
      Macrosiphum euphorbiae (Thomas), than on the Mi-lacking cultivars Moneymaker, Rio
      Fuego and Roma. When data of Mi-bearing plants were pooled, the mean values for
      daily infestation and pupal production of B. tabaci were significantly lower than
      those of Mi-lacking plants. This reflected a level of antixenosis- and antibiosis
      based resistance in commercial tomato and indicated that Mi, or another closely
      linked gene, might be implicated in a partial resistance which was not associated
      either with the presence of glandular trichomes or their exudates. These findings
      support the general hypothesis for the existence of similarities among the
      resistance mechanisms to whiteflies, aphids and nematodes in commercial tomato
      plants.

PMID- 10948377
TI  - A European pest to control a new zealand weed: investigating the safety of
      heather beetle, Lochmaea suturalis (Coleoptera: Chrysomelidae) for biological
      control of heather, Calluna vulgaris.
AB  - Heather, Calluna vulgaris (L.) Hull, is a serious invasive weed in the central
      North Island of New Zealand, especially in Tongariro National Park, a World
      Heritage Area. Heather beetle, Lochmaea suturalis (Thomson), is a foliage-feeding
      pest of Calluna in Europe, that was selected as the most promising biological
      control agent for introduction into New Zealand, because it causes high levels of
      damage to Calluna in Europe. Host-range tests indicated that L. suturalis poses a
      negligible threat to native New Zealand plants. Cultivars of Calluna grown as
      ornamentals are suitable food plants, but are unlikely to be severely affected
      because L. suturalis requires a damp understorey of moss or litter for successful
      oviposition and pupation, which is rarely present in gardens. However, mosses and
      litter occurring under Calluna stands in Tongariro National Park are suitable
      substrates for eggs and pupae. Lochmaea suturalis released in New Zealand has
      been freed of parasitoids and a microsporidian disease that attack the beetles in
      Europe.

PMID- 10948378
TI  - A leaf-section bioassay for evaluating rice stem borer resistance in transgenic
      rice containing a synthetic cry1Ab gene from Bacillus thuringiensis berliner.

PMID- 10948379
TI  - Medicinal herbs: naturally safe.

PMID- 10948380
TI  - Hepatotoxicity of botanicals.
AB  - OBJECTIVE: Hepatic impairment resulting from the use of conventional drugs is
      widely acknowledged, but there is less awareness of the potential hepatotoxicity
      of herbal preparations and other botanicals, many of which are believed to be
      harmless and are commonly used for self-medication without supervision. The aim
      of this paper is to examine the evidence for hepatotoxicity of botanicals and
      draw conclusions regarding their pathology, safety and applications. DESIGN:
      Current literature on the hepatotoxicity of herbal drugs and other botanicals is
      reviewed. The aetiology, clinical picture and treatment of mushroom (Amanita)
      poisoning are described. RESULTS: Hepatotoxic effects have been reported for some
      Chinese herbal medicines (such as Jin Bu Huan, Ma-Huang and Sho-saiko-to),
      pyrrolizidine alkaloid-containing plants, germander (Teucrium chamaedrys),
      chaparral (Larrea tridentata), Atractylis gummifera, Callilepsis laureola, and
      others. The frequency with which botanicals cause hepatic damage is unclear.
      There is a lack of controlled treatment trials and the few studies published to
      date do not clarify the incidence of adverse effects. Many plant products do not
      seem to lead to toxic effects in everyone taking them, and they commonly lack a
      strict dose-dependency. For some products, such as Sho-saiko-to, the picture is
      confused further by demonstrations of hepatoprotective properties for some
      components. Mushroom poisoning is mostly due to the accidental consumption of
      Amanita species. Treatment with silymarin, thioctic acid, penicillin and liver
      transplantation have been shown to be effective but require early diagnosis.
      CONCLUSIONS: Severe liver injury, including acute and chronic abnormalities and
      even cirrhotic transformation and liver failure, has been described after the
      ingestion of a wide range of herbal products and other botanical ingredients,
      such as mushrooms. It is concluded that in certain situations herbal products may
      be just as harmful as conventional drugs.

PMID- 10948381
TI  - The role of vitamins in the prevention and control of anaemia.
AB  - OBJECTIVE: While iron deficiency is regarded as the major cause of nutritional
      anaemia, changes in vitamins A, B12, C and E, folic acid and riboflavin status
      have also been linked to its development and control. This paper provides a
      systematic review of vitamin supplementation trials relating to the control of
      nutritional anaemia. METHODS: A MEDLINE search was used to find reports of
      vitamin supplementation trials that reported changes in anaemia or iron status.
      RESULTS: Vitamin A can improve haematological indicators and enhance the efficacy
      of iron supplementation. Both folate and vitamin B12 can cure and prevent
      megaloblastic anaemia. Riboflavin enhances the haematological response to iron,
      and its deficiency may account for a significant proportion of anaemia in many
      populations. Vitamin C enhances the absorption of dietary iron, although
      population-based data showing its efficacy in reducing anaemia or iron deficiency
      are lacking. Vitamin E supplementation given to preterm infants has not reduced
      the severity of the anaemia of prematurity. Vitamin B6 effectively treats
      sideroblastic anaemia. Multivitamin supplementation may raise haemoglobin (Hb)
      concentration, but few studies have isolated the effect of multivitamins from
      iron on haematological status. CONCLUSIONS: In general, the public health impact
      of vitamin supplementation in controlling anaemia is not clear. Neither are the
      complex interactions involving multiple vitamins in haematopoiesis sufficiently
      understood to explain the observed variability in haematological responses to
      vitamins by age, population, vitamin mixture and dosages. Further research is
      needed to understand the roles of individual and combined vitamin deficiencies on
      anaemia to design appropriate micronutrient interventions to prevent anaemia.

PMID- 10948382
TI  - Comparison of a dietary record using reported portion size versus standard
      portion size for assessing nutrient intake.
AB  - OBJECTIVE: Because the percentage of missing portion sizes was large in the
      Aerobics Center Longitudinal Study (ACLS), careful consideration of the accuracy
      of standard portion sizes was necessary. The purpose of the present study was to
      investigate the consequences of using standard portion sizes instead of reported
      portion sizes on subjects' nutrient intake. METHODS: In 2307 men and 411 women,
      nutrient intake calculated from a 3-day dietary record using reported portion
      sizes was compared with nutrient intake calculated from the same record in which
      standard portion sizes were substituted for reported portion sizes. RESULTS: The
      standard portion sizes provided significantly lower estimates (>/= 20%) of energy
      and nutrient intakes than the reported portion sizes. Spearman correlation
      coefficients obtained by the two methods were high, ranging from 0.67 to 0.93.
      Furthermore, the agreement between both methods was fairly good. Thus, in the
      ACLS the use of standard portion sizes rather than reported portion sizes did not
      appear to be suitable to assess the absolute intake at the group level, but
      appeared to lead to a good ranking of individuals according to nutrient intake.
      These results were confirmed by the Continuing Survey of Food Intake by
      Individuals (CSFII), in which the assessment of the portion size was optimal.
      When the standard portion sizes were adjusted using the correction factor, the
      ability of the standard portion sizes to assess the absolute nutrient intake at
      the group level was considerably improved. CONCLUSIONS: This study suggests that
      the adjusted standard portion sizes may be able to replace missing portion sizes
      in the ACLS database.

PMID- 10948383
TI  - Food patterns defined by cluster analysis and their utility as dietary exposure
      variables: a report from the Malmo Diet and Cancer Study.
AB  - OBJECTIVE: To explore the utility of cluster analysis in defining complex dietary
      exposures, separately with two types of variables. DESIGN: : A modified diet
      history method, combining a 7-day menu book and a 168-item questionnaire,
      assessed dietary habits. A standardized questionnaire collected information on
      sociodemographics, lifestyle and health history. Anthropometric information was
      obtained through direct measurements. The dietary information was collapsed into
      43 generic food groups, and converted into variables indicating the per cent
      contribution of specific food groups to total energy intake. Food patterns were
      identified by the QUICK CLUSTER procedure in SPSS, in two separate analytical
      steps using unstandardized and standardized (Z-scores) clustering variables.
      SETTING: : The Malmo Diet and Cancer (MDC) Study, a prospective study in the
      third largest city of Sweden, with baseline examinations from March 1991 to
      October 1996. SUBJECTS: A random sample of 2206 men and 3151 women from the MDC
      cohort (n = 28 098). RESULTS: Both variable types produced conceptually well
      separated clusters, confirmed with discriminant analysis. 'Healthy' and 'less
      healthy' food patterns were also identified with both types of variables.
      However, nutrient intake differences across clusters were greater, and the
      distribution of the number of individuals more even, with the unstandardized
      variables. Logistic regression indicated higher risks of past food habit change,
      underreporting of energy and higher body mass index (BMI) for individuals falling
      into 'healthy' food pattern clusters. CONCLUSIONS: The utility in discriminating
      dietary exposures appears greater for unstandardized food group variables. Future
      studies on diet and cancer need to recognize the confounding factors associated
      with 'healthy' food patterns.

PMID- 10948384
TI  - Use of food labels and beliefs about diet-disease relationships among university
      students.
AB  - OBJECTIVE: The purpose of this study was to measure the reported use of nutrition
      information on food labels by a population of university students and to
      determine if label users differed from non-users in terms of gender and specific
      beliefs related to label information and diet-disease relationships, specifically
      fat and heart disease and fibre and cancer. DESIGN: A single-stage cluster
      sampling technique was used. Data was obtained using a self-administered,
      validated questionnaire. SETTING: The present investigation took place at the
      University of Saskatchewan, Canada in the autumn of 1997. SUBJECTS: : A total of
      553 students in randomly selected classes in the College of Arts and Science took
      part in the survey (92% response rate). The sample consisted of roughly equal
      numbers of males and females, most between the ages of 18 and 24. RESULTS: There
      were approximately equal numbers of label users and non-users among males, while
      label users outnumbered non-users by almost four to one among females. The
      importance of nutrition information on food labels was the only belief that
      differed significantly between label users and non-users for both sexes. For
      females, no other beliefs distinguished label users from non-users. However, for
      males, significant differences were found between label users and non-users on
      the beliefs that nutrition information is truthful and that a relationship
      between fibre and cancer exists. CONCLUSIONS: Females appear to use food labels
      more often than do males. The only consistently observed difference between label
      users and non-users (male and female) was that users believed in the importance
      of nutrition information on food labels while non-users did not.

PMID- 10948385
TI  - An evaluation of food photographs as a tool for quantifying food and nutrient
      intakes.
AB  - OBJECTIVE: To evaluate the errors incurred by young adults using single portion
      size colour food photographs to quantify foods and nutrients consumed at six
      meals on two non-consecutive days. DESIGN: Breakfast menus remained the same for
      the 2 days; but lunch and dinner menus varied. The amounts of food eaten by
      individuals were determined by weighing individual serving dishes pre- and post
      consumption. The day after eating, all foods consumed were quantified in terms of
      fractions or multiples of the amounts shown in the food photographs. SUBJECTS:
      Thirty adult volunteers (15 male, 15 female), aged 18-36 years, completed the
      protocol for day one; 27 (90%) completed day two. RESULTS: Some foods were more
      difficult to quantify accurately than others. The largest error range was -38. 9%
      to +284.6% (cheese), whereas the smallest errors were incurred for juice (-21.5%
      to +34.6%, day one). All subjects who consumed muesli (day one) overestimated
      (+3.7% to +113.7%). No other foods were consistently over- or underestimated. For
      foods consumed at breakfast by the same subjects on both days, individual
      estimation errors were inconsistent in magnitude and/or direction. At the group
      level, most nutrients were estimated to within +/-10% of intake; exceptions were
      thiamin (+10.5%, day one) and vitamin E (-10.1%, day one; -15.3%, day two).
      Between 63% and 80% of subjects were correctly classified into tertiles on the
      basis of estimated intakes. CONCLUSIONS: Despite some large food quantification
      errors, single portion size food photographs were effective when used to estimate
      nutrient intakes at the group level. It remains to be established whether, under
      the conditions used in this study, more photographs per food would improve
      estimates of nutrient intake at the individual level.

PMID- 10948386
TI  - Predicting under- and overnutrition among women of reproductive age: a population
      based study in central Java, Indonesia.
AB  - OBJECTIVES: To evaluate changes over 1 year in weight and body mass index (BMI)
      among a population-based sample of non-pregnant women in Indonesia and to
      identify risk factors for developing under- and overnutrition. DESIGN: Cross
      sectional studies in 1996 and 1997 in the same population. SETTING: Purworejo
      District, central Java, Indonesia. SUBJECTS: Non-pregnant women (n = 4132) aged
      15-49 years of age who participated in both 1996 and 1997. Based on BMI, women
      were classified as having chronic energy deficiency (CED), and as being either of
      normal weight or obese. RESULTS: The mean height of the women was below the fifth
      percentile of international standards. In 1996, 16.2% had CED, 72.2% were normal
      and 11.6% were obese. In 1997, the corresponding figures were 14.4%, 71.2% and
      14.3%, respectively, revealing a significant mean increase in weight and BMI.
      Among women classified as normal in 1996, 3.0% developed CED in 1997. Significant
      risk factors for developing CED were experiences of child deaths and non-use of
      contraceptives. Among women classified as normal in 1996, 5.3% developed obesity
      in 1997. Here, significant risk factors included most indicators of wealth as
      well as occupation. CONCLUSIONS: The results should be important for future
      efforts to prevent CED and obesity in the general population; conditions which
      are both associated with health risks.

PMID- 10948388
TI  - Types of drinks consumed by infants at 4 and 8 months of age: a descriptive
      study. The ALSPAC Study Team.
AB  - OBJECTIVE: To document the type and volume of drinks given to infants and
      investigate whether giving supplementary drinks leads to reduced milk
      consumption. DESIGN: Carers were asked to record all drinks consumed by the
      infants in a 24-hour period at two ages, detailing the types and volume taken.
      SETTING: The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC).
      SUBJECTS: A randomly chosen population sample of over 1000 infants at 4 and 8
      months of age. RESULTS: The different types of milk feed were used to group
      infants, compare volumes consumed and look at the use of non-milk drinks. The
      average volume of drinks consumed over 24 hours at 4 months was 861 ml and at 8
      months was 662 ml. At 4 months 69.7% consumed infant formula and 43.0% breast
      milk. The mean volume of milk consumed by those having only formula was 802 ml
      and for those having only breast milk was estimated at 850 ml. The volumes of
      milks consumed were slightly lower in the groups who also had supplementary
      drinks. A quarter of infants were given fruit drinks and 14.6% herbal drinks.
      Supplementary drinks and solids were more likely to be given to formula-fed than
      breast-fed infants. At 8 months, formula milk was consumed by 71.4% and breast
      milk use had decreased (22.9%) but fruit drink use had increased (squash/cordial:
      55.8%, fruit juice: 14.9%), with 13.9% of infants having no infant milk at all.
      More infants were fed formula milk and less were fed cows' milk compared with a
      nationally representative British study conducted 5 years earlier. CONCLUSIONS:
      Many infants were given supplementary drinks by 4 months; there is some evidence
      that this led to a small reduction in milk intake. A minority were not being
      given infant milks at all by 8 months, contrary to British infant feeding
      recommendations.

PMID- 10948387
TI  - The influence of recipe modification and nutritional information on restaurant
      food acceptance and macronutrient intakes.
AB  - OBJECTIVE: To examine the influences of nutritional information and consumer
      characteristics on meal quality expectations, food selection and subsequent
      macronutrient intakes of consumers offered a reduced-fat option in a restaurant.
      DESIGN: A target, full-fat (FF) main restaurant meal option was developed in a
      version substantially reduced in fat and energy (RF). Restaurant patrons were
      randomly placed into one of four treatment groups varying in provision of menu
      information about the target dish, and the actual version of that dish served (if
      ordered). A full-fat blind (FFB) control group was given no nutritional
      information in the menu and was served the FF version. The other three groups
      were all served the modified RF version: (i) reduced-fat blind (RFB), who were
      given no nutritional information; (ii) reduced-fat informed (RFI), who were given
      nutritional information; and (iii) reduced-fat informed with details (RFID), who
      were given the same nutritional information plus recipe modification details.
      Subjects rated their expected and actual liking, the pleasantness of taste,
      texture and appearance of the dish, how well the dish matched their expectations,
      and the likelihood of purchase again. Additional measures included the other dish
      selections, sociodemographic and attitudinal information. SETTING: A silver
      service (training) restaurant. SUBJECTS: Members of the public (n = 279)
      consuming meals in the restaurant. RESULTS: The presence of nutritional
      information on the menu did not significantly increase subsequent intakes of
      energy and fat from the rest of the meal, and did not significantly influence
      sensory expectations or post-meal acceptance measures (which also did not differ
      between the FF and RF versions). Consumer characteristics relating to fat
      reduction attitudes and behaviours were significantly related to the selection of
      different dishes. CONCLUSIONS: Provision of RF alternatives in a restaurant can
      have significant positive dietary benefits. Menu nutritional information did not
      affect measures of meal acceptance. Further studies should identify which types
      of information formats might be most effective in enhancing the selection of
      'healthy' options.

PMID- 10948389
TI  - Sociodemographic determinants of perceived influences on food choice in a
      nationally representative sample of Irish adults.
AB  - OBJECTIVE: To identify the most important motivations for food choice from the
      point of view of the consumer in the Irish population, and to characterize those
      subjects who do and do not regard nutrition as a significant consideration in
      food choice. DESIGN: As part of a pan-European Union (EU) survey on consumer
      attitudes to food, nutrition and health, a quota-controlled, nationally
      representative sample of Irish adults (n = 1009) aged 15 years upwards, completed
      an interview-assisted, close-ended questionnaire. Subjects selected three
      factors, from a list of 15, which they believed had the greatest influence on
      their food choice. SETTING: The interviews for the survey were conducted in
      subjects' homes. RESULTS: 'Quality/freshness of food' was the most frequently
      selected food choice factor (51%) followed by 'taste' (43%) and 'trying to eat a
      healthy diet' (36%). Female gender, increasing age and higher levels of education
      were found to be independent sociodemographic factors affecting the selection of
      'trying to eat a healthy diet' as an important factor in food choice.
      CONCLUSIONS: Although included in the top five most frequently selected factors
      affecting food choice, nutrition/healthy eating does not appear to have top
      priority for the majority of Irish adults. There are differences between the
      various sociodemographic groups within the population; males and younger subjects
      appear to require specific nutrition promotion messages.

PMID- 10948390
TI  - Breakfast cereal consumption in young children: associations with non-milk
      extrinsic sugars and caries experience: further analysis of data from the UK
      National Diet and Nutrition Survey of children aged 1.5-4.5 years.
AB  - OBJECTIVE: This study examined the relationship between breakfast cereal
      consumption and non-milk extrinsic sugars (NMES) intake and the possible
      implications of this for caries in preschool children. METHODS: Data from the
      1995 UK National Diet and Nutrition Survey (NDNS) of children aged 1.5-4.5 years
      were reanalysed. Four-day weighed food records and dental examinations were
      available on 1450 children living in private households in Britain. Children were
      classified by tertiles (age-adjusted) according to the proportion of energy
      derived from breakfast cereals, and the amount of NME sugar from cereals. There
      were no significant differences in social class background between any of the
      groups. RESULTS: Children with diets high in breakfast cereals as a proportion of
      total energy (top third) had lower proportional intakes of NMES, compared with
      low consumers of cereals (lowest third). Consumption of sweetened cereals was
      positively associated with NMES intake. However, caries experience was unrelated
      to breakfast cereal consumption, whether presweetened or not. CONCLUSIONS:
      Although presweetened cereals are relatively high in NMES, their cariogenic
      potential is probably minimal in the circumstances in which they are normally
      consumed.

PMID- 10948391
TI  - Food intake patterns and gallbladder disease in Mexican Americans.
AB  - OBJECTIVE: Results of previous studies on diet and gallbladder disease (GBD),
      defined as having gallstones or having had surgery for gallstones, have been
      inconsistent. This research examined patterns of food intake in Mexican Americans
      and their associations with GBD. DESIGN: Cross-sectional. SUBJECTS: The study
      population included 4641 Mexican Americans aged 20-74 years who participated in
      the 1988-94 third National Health and Nutrition Examination Survey (NHANES III).
      GBD was diagnosed by ultrasound. Food intake patterns were identified by
      principal components analysis based on food frequency questionnaire responses.
      Component scores representing the level of intake of each pattern were
      categorized into quartiles, and prevalence odds ratios (POR) were estimated
      relative to the lowest quartile along with 95% confidence intervals (CI).
      RESULTS: There were four distinct patterns in women (vegetable, high calorie,
      traditional, fruit) and three in men (vegetable, high calorie, traditional).
      After age adjustment, none were associated with GBD in women. However, men in the
      third (POR = 0.42, 95%CI 0.21-0.85) and fourth (POR = 0.53, 95%CI 0.28-1.01)
      quartiles of the traditional intake pattern were half as likely to have GBD as
      those in the lowest quartile. CONCLUSIONS: These findings add to a growing
      literature suggesting dietary intake patterns can provide potentially useful and
      relevant information on diet-disease associations. Nevertheless, methods to do so
      require further development and validation.

PMID- 10948392
TI  - The epidemiology of iodine deficiency disorders (IDD) in Yemen.
AB  - OBJECTIVE: This first nationwide survey was undertaken to estimate the prevalence
      rates and severity of iodine deficiency disorders (IDD) and the proportion of
      households consuming iodized salt. DESIGN: The country was stratified into two
      ecological zones and 30 clusters (primary schools) from each zone, including the
      required numbers of pupils, were selected randomly. A subsample of pupils
      provided urine and salt samples for the determination of urinary iodine excretion
      (UIE) and presence of iodate, respectively. SETTING: Yemen. SUBJECTS: There were
      a total of 2984 pupils aged 6-12 years of whom 2003 were boys and 981 girls. The
      majority (1800) pupils were from the lowland/coastal areas (zone II) and the rest
      (1184) from the mountainous regions (zone I). RESULTS: The total goitre rates
      (TGR) in the whole country, zones II and I were 16.8%, 31.1% and 7.4%,
      respectively. The TGR in zone I for males was 32.8% and 27.3% for females, while
      in zone II the corresponding rates were 8.1% and 5.9%, respectively, and the
      differences were not statistically significant. Only three cases of visible
      goitres were encountered. The median UIE levels in zones I, II and the whole
      country were 13.6, 18.9 and 17.3 microg dl-1, respectively. Based on UIE cut-off
      points recommended by WHO, IDD was severe in 4.7% of pupils in zone I and 2.6% in
      zone II. Mild and moderate IDD were found in 18.5% and 8.7% of the pupils
      respectively. Nearly 70% of the surveyed pupils had UIE values of >/= 10 microg
      dl-1 (no deficiency). Girls had relatively better iodine nutrition as suggested
      by higher levels of median UIE. In addition, across all age groups median UIE
      values were above 10 microg dl-1. Over half of the households consumed iodized
      salt. CONCLUSIONS: Since the introduction of universal salt iodization in 1996
      both the prevalence and severity of IDD in Yemen were reduced markedly and Yemen
      can now be classified as a country with a mild IDD problem. However, the low
      level of households consuming iodized salt may hamper the goal of IDD
      elimination.

PMID- 10948393
TI  - Application of multimedia in electronic communication of scientific information.

PMID- 10948394
TI  - Pharmacokinetics tricks and traps: flip-flop models.

PMID- 10948395
TI  - Clinical significance of bioequivalence and interchangeability of narrow
      therapeutic range drugs: focus on warfarins.

PMID- 10948396
TI  - Prediction of plasma levels of aminoglycoside antibiotic in patients with severe
      illness by means of an artificial neural network simulator.
AB  - PURPOSE: The purpose of this work was to predict plasma peak and trough levels of
      an aminoglycoside antibiotic in patients with severe illness in an intensive care
      unit by a novel approach. Plasma levels were predicted based on the values of 15
      physiological measurements using an artificial neural network (ANN) simulator.
      METHOD: A data set of 15 physiological measurements for 30 patients was used to
      develop the model. The ANN structure consisted of three layers: an input layer
      comprised of 15 processing elements, a hidden layer comprised of 10 processing
      elements with a sigmoid function as an activation function, and an output layer
      of two processing elements (peak and trough levels). The weight between neurons
      was trained according to the delta rule back-propagation of errors algorithm.
      Predicted values were obtained by "leave-one-out" experiments by both ANN and
      multiple linear regression analysis (MLRA). RESULTS: The correlation coefficients
      between observed and predicted values obtained by ANN prediction using
      standardized data sets were r=0.825 and r=0.854 for peak and trough levels,
      respectively. The correlation coefficients obtained by MLRA were r=0. 037 and
      r=0.276 for peak and trough levels, respectively. These results indicate that ANN
      shows better performance in prediction of aminoglycoside plasma levels from
      patients' physiological measurements than MLRA. CONCLUSIONS: Prediction of plasma
      levels of antibiotic in patients with severe illness by ANN was superior to the
      standard statistical method. Standardization of input data was found to be
      important for better prediction. ANN has some advantages over standard
      statistical methods, as it can recognize complex relationships in the data.

PMID- 10948397
TI  - In vitro evaluation of percutaneous absorption of an acyclovir product using
      intact and tape-stripped human skin.
AB  - PURPOSE: To evaluate the use of a flow-through diffusion cell system to assess
      the absorption and penetration characteristics of drug (acyclovir) products.
      METHODS: In vitro studies were performed to assess the absorption/penetration of
      acyclovir using a flow-through diffusion cell system with human skin sections
      obtained from 19 healthy women following mammoplasty. The skin sections, 200-400
      microm thick, were prepared using a dermatome. Acyclovir ointment (approximately
      10 mg) spiked with (3)H-labelled acyclovir was applied onto the stratum
      corneum/epidermis side. The skin sections were continually perfused on the dermis
      side with sterilized culture medium, Buffered Hanks' Balanced Salt Solution,
      saturated with a CO(2)/O(2) (5/95%). RESULTS: After 24 hours, the percentages of
      acyclovir-derived radioactivity (based on dose applied) in different components
      were as follows: stratum corneum (SC), 0.20+0.28; viable skin (VS), 0.40+0.38;
      effluent fluid (EF), 0.25+0.53. A second set of experiments was performed using
      tape stripped (10X) skin sections. Levels of acyclovir-derived radioactivity were
      VS, 1.21+1.43 and EF, 2.65+2.61, which were threefold higher (p < 0.05) for VS
      and elevenfold higher (p < 0.05) for EF compared to the results obtained with the
      intact skin sections. CONCLUSIONS: The SC is the main barrier layer for the
      penetration of acyclovir through human skin. The use of the flow-through
      diffusion cell system provides an appropriate in vitro model to assess the
      absorption/penetration of acyclovir through human skin layers and therefore can
      potentially be used for dermal formulation characterization and development.

PMID- 10948398
TI  - In vitro anti-hepatitis B virus activities of 5"-O-myristoyl analogue derivatives
      of 3"-fluoro-2",3"-dideoxythymidine (FLT) and 3"-azido-2",3"-dideoxythymidine
      (AZT).
AB  - PURPOSE: The objective of this study was to evaluate a dual action prodrug
      concept wherein an unnatural myristic acid analogue is coupled via an ester
      moiety to the 5'-position of FLT or AZT. Subsequent intracellular cleavage of the
      prodrug ester would simultaneously release FLT or AZT that could inhibit reverse
      transcriptase (RT), and the myristic acid analogue that could inhibit myristoyl
      CoA:protein N-myristoyltransferase (NMT). METHODS: Cytotoxicity (2.2.15 cell
      culture), and anti-hepatitis B activity of 5'-O-myristoyl analogue prodrug
      derivatives of FLT and AZT (2-8) were evaluated in vitro using human liver
      hepatitis B virus (HBV) producing 2.2.15 cell lines. RESULTS: The 5'-O-(12
      methoxydodecanoyl) ester derivatives of AZT (2, EC(50) = 2. 7 +/- 0.3 microM;
      CC(50)= 727 +/- 19 microM) and FLT (4, EC(50)= 2.8 +/- 0.3 microM; CC(50)= 186 +/
      20 microM) were the most effective anti-hepatitis B virus (anti-HBV) compounds
      of this series in a replication assay. In the series of 5'-O-myristic acid
      analogue ester prodrug derivatives of FLT, the relative anti-HBV potency order
      was MeO(CH(2))(11)CO(2)- > N(3)(CH(2))(11)CO(2)- and Br(CH(2))(11)CO(2)- >
      EtS(CH(2))(n)CO(2)- (n = 10 or 11) > Me(CH(2))(12)CO(2)- (myristoyl).
      CONCLUSIONS: The in vitro data suggest that the 5'-O-myristoyl analogue prodrug
      concept offers a potential drug design approach to design dual acting antiviral
      agents, with superior pharmacokinetic, biodistribution, reduced cytotoxicity
      and/or increased efficacy. In this regard, the 5'-O-(12-methoxydodecanoyl)
      prodrug ester of 3'-thia-3'-deoxythymidine (3TC) may offer the greatest potential
      for the treatment of HBV infection.

PMID- 10948400
TI  - [On diagnosis and prophylaxis of asthenoneurotic syndrome in cosmonauts in long
      term mission].
AB  - Based on longer than 20 years experience of observation and investigation of the
      neuropsychic state of cosmonauts in long-term missions to the space stations and
      volunteers in ground studies of some of the spaceflight (SF) effects, principles
      of diagnostics, prophylaxis and correction of asthenoneurotic and psychoasthenic
      disorders in members of long-term orbital mission have been established. The
      authors give consideration to the most probable pathophysiological mechanisms of
      these disorders during SF and some potential lines of exploration and development
      of countermeasures against and methods for correction of the psychoneurologic
      disorders during long-term missions.

PMID- 10948401
TI  - [Some medical problems of piloted mission to Mars].
AB  - Medical provisions to planetary missions take in a wide spectrum of medical,
      engineering and organizational issues the goal of which is to provide good living
      conditions for humans in space, and to ensure physical and psychic health and
      performance of crew members during research activities on the Martian surface and
      soon after return to Earth. The article carefully reviews the problems of
      defining conceptual approaches to medical support in a mission to Mars. These
      approaches are grounded on the analysis of medical experience of prolonged
      orbital missions and prognosis of physiological shifts due to extension of
      mission up to 2 to 3 years including the period of stay on the Martian surface.
      Special attention is given to the key medical aspects of the mission, i.e.
      medical monitoring, countermeasures (including utilization of a short-arm
      centrifuge) against the adverse effects of microgravity on crew health and
      keeping-up useful skills and knowledge.

PMID- 10948399
TI  - The effects of circulating antigen on the pharmacokinetics and
      radioimmunoscintigraphic properties of 99m Tc labelled monoclonal antibodies in
      cancer patients.
AB  - PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and
      radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb)
      used to detect cancer. METHODS: The effects of circulating antigen in female
      cancer patients are explored and their effects on the ability of these MAbs to
      effectively perform as RIS agents noted. To illustrate the effects of circulating
      antigen, data using MAb B43.13 (OVAREX, AltaRex Corp., Waltham, MA, USA) from a
      Pilot study in ovarian cancer patients are presented. The results from a Phase II
      study of MAb 170H.82 (Tru-Scint AD, BIOMIRA INC., Edmonton, Alberta, Canada) in
      patients with primary and locally recurrent breast cancer were used to portray
      the biodistribution patterns when no circulating antigen is present. Data from
      planar gamma camera images were obtained for both groups and used for
      pharmacokinetic and radiation dosimetry analyses. RESULTS: A pharmacokinetic
      analysis indicated a shorter residence time and higher clearance of (99m)Tc-MAb
      B43.13 that was ascribed in part to the circulating CA 125 antigen in this group
      of ovarian cancer patients. CONCLUSION: These clearance patterns resulted in
      acceptable, though higher radiation doses to the spleen and urinary bladder wall
      for these patients when compared to the MAb-170H.82 group. Both MAbs were found
      to produce acceptable radioimmunoscintigraphic images

PMID- 10948402
TI  - [Protein turnover during and after extended space flight].
AB  - A 15N-glycine tracer technique was used to study protein turnover in four Russian
      cosmonauts and two U.S. astronauts who had spent long time aboard the Russian
      orbital station MIR. As was shown, in space flight protein synthesis falls by 46%
      on the average, which substantially exceeds estimations made on the basis of data
      about bed-rested human subjects. Reduction in protein synthesis during space
      flight is connected with the negative energy balance; therefore, it appears
      imperative to keep balance between energy intake (foodstuffs) and expenditure by
      cosmonauts on long-term mission.

PMID- 10948403
TI  - [Effect of inclination angles of supporting surfaces og aircraft seat on pilot's
      working capacity in long-duration flight].
AB  - Results of experimental evaluation of the performance of pilots bound to stay up
      to 24 hrs in the working pose as a function of inclination of supporting surfaces
      (backrest and seat) are presented. Small inclination angles (up to 23 degrees)
      were found to be more provocative of discomfort, painful sensations and work
      deterioration characterized by higher intensity. It was shown that periodic
      change of the seatback inclination is an effective way to prevent fatigue in
      pilots on long-duration flights and to prolong time of comfortable stay in forced
      posture up to 12-16 hrs. The data on the time of comfortable stay and dynamics of
      pilot's performance as a function of angles of supporting surfaces of the seat
      laid the grounds to determination of the best combination to provide comfort to
      pilot on flight.

PMID- 10948405
TI  - [Connective tissue under emotional stress].
AB  - The data pointing to morphofunctional changes in connective tissues of rats after
      exposure to acute experimental stress are presented. These changes were shown to
      be dependent on resistance of animals to emotional stress. Animals predisposed to
      the emotional stress developed more pronounced changes in connective tissues
      evident as tissue hemorrhages and edema, accumulation of hyaluronic structures,
      and degranulation and devastation of mast cells. Water immersion stress in these
      rats resulted in a significant decrease in uronic acids in the skin, damages of
      endotheliocytes and disruption of plasmalemma and basal membrane of the wall of
      the aortic arch ascending segment.

PMID- 10948404
TI  - [Repeated exposure in hypergravity: morphology of locus coeruleus, hypothalamic
      paraventricular nucleus and vagal nerve dorsal nucleus in rats].
AB  - As compared to analogous single rotation at 2 g and in contrast to 5-d single and
      repeated exposures to Coriolis accelerations, repeated 5-day hypergravity (2 g
      generated by centrifuge rotation) gave rise to structural alterations in rat's
      neurons of locus coeruleus, vasopressinergic neurons of the lateral magnocellular
      subnucleus paraventricular nucleus and nervi vagi dorsal nucleus suggesting
      involvement of these structures of brain in the mechanism of facilitation of
      adaptation to repeated long-term hypergravity. Results of the study point to the
      ability of mammals to remember changes in gravity. Findings of the study may help
      develop an algorithm of intermittent exposure to artificial gravity aboard space
      vehicle.

PMID- 10948406
TI  - [Probability of lens opacity and mature cataracts due to irradiation at various
      LET values].
AB  - The paper reviews experimental and clinical data on the incidence of opacity of
      the lens and cataract development in animals and humans due to exposure to
      different types of radiation. Cataractogenous effectiveness of fast neutrons,
      accelerated ions of carbon, helium, neon and argon with the energy of 300
      MeV/nucleon, and 137Cs gamma-radiation was compared. Analysis of the incidence of
      opacity of the lens in consequence of low doses gave high RBE estimates (from 10
      to 40). The extremely high cataractogenous effectiveness of accelerated ions
      makes on thing that the existent space radiation limits, particularly in part of
      the GCR effects on the lens and permissible doses for cosmonauts, should be
      reconsidered towards mitigation. The authors discuss issues of threshold
      radiation doses that do not markedly increase incidence and rate of the lens
      opacity development in the post-exposure period.

PMID- 10948407
TI  - [Survivability and morphologic anomalies in higher plants wolffia arrhiza
      following exposure to heavy ions of the galactic space radiation].
AB  - Experimental data on the effects of spaceflight factors, space radiation in
      particular, on higher plant Wolffia arrhiza firstly exposed in the "Bioblock"
      assembly and measurements made by physical track detectors of heavy ions (HI) are
      presented. Death of individual Wolffia plants and morphologic anomalies were the
      basic evaluation criteria. The peculiar feature of this biological object
      consists in the possibility to reveal delayed effects after 1-2 months since
      space flight as Wolffia has a high rate of vegetative reproduction. German
      investigators through microscopic examination of track detectors performed
      identification of individual plants affected by HI. With specially developed
      software and a coordinate system of supposition of biolayers and track detectors
      with the accuracy of 1 micron, tracks and even separate sections of individual HI
      tracks were determined in biological objects. Thereafter each Wolffia plant hit
      by HI was examined and data were compared with other variants. As a result,
      correlation between Wolffia death rate and morphologic anomalies were determined
      at different times post flight and topography of HI tracks was found. It is
      hypothesized that morphological anomalies in Walffia were caused by direct hits
      of plant germs by heavy ions or close passage of particles.

PMID- 10948408
TI  - [Geomagnetic effects on cortico-caudal mechanisms of auditory stimuli processing
      in cats].
AB  - Impacts of geomagnetic disturbances on parameters of an early complex of evoked
      potentials (EP, up to 100 ms) in the temporal cortex (TC) and the head of caudate
      nucleus (HCN) due to the auditory stimulus (click, 85 dB) were evaluated in 12
      conscious cats. Mean values of the peak time amplitude, expressiveness of each
      component and latent period were determined. Indices D, H and Z were used to
      evaluate the magnetic activity. Experimental animals in group-1 displayed an
      increase in latency of cortical EP against weakened EP expressiveness in the
      right hemisphere. In HCN EP expressiveness showed a rise in the left hemisphere.
      In group-2, the latent period of cortical EP grew in parallel to the amplitude
      and peak negative component. The latent period of caudal EP diminished whereas
      expressiveness and amplitude of EP components increased. The data suggest that
      geomagnetic disturbances suppress the cortical reactivity to exteroceptive
      stimuli and raise the functional activity of the cerebral inhibitory components,
      as is the caudate nucleus.

PMID- 10948409
TI  - [Effect of acoustic exposure of various duration on the system of insulin
      regulation in human].
AB  - Effects of various periods of acoutic noise on the dynamics of insular indices
      and associated biochemical parameters were studied in 22 male volunteers aged 20
      25. On a balance, experimental and literary data suggest that acoustic noise can
      increase insulin in blood and cause, during prolonged chronic exposure,
      development of insulin resistance. At the same time, in individuals with signs of
      insulin resistance or hyperinsulinemia tolerance for the factors of flying
      activity was reduced; thus, insulin resistance may be considered a premorbid
      background for metabolic shifts and symptoms of stressogenic illnesses in a
      delayed period. Changes revealed in the study can be used as biochemical criteria
      of unfavourable effects of acoustic noise.

PMID- 10948410
TI  - [Chrono-ecological analysis of population health and ways of its recreation].
AB  - Reported are results of multiyear observation of the structure of individual and
      population health in Vladikavkaz, and the authors' concept of health recovery and
      protection through application of modern high technologies of active
      chronoadaptation to extreme living conditions. The proposed methods of active
      chronoadapation, i.e. phytocorrection and phytopro-phylaxis, reflexocorrection,
      bioradiological correction, bioresonance chronolasercorrection can be also of
      interest for aerospace medicine.

PMID- 10948411
TI  - Glutathione circadian rhythm in duodenal mucosa of fasted rats.
AB  - Duodenal ulcer is a relevant clinical condition, but information about circadian
      rhythms of the duodenum is scarce. While the chronobiological model of gastric
      ulcerogenesis has been partly demonstrated, the time dependent variations of
      protective and aggressive factors of the duodenal mucosa have not yet been
      sufficiently documented. The aim of this study is to document the duodenal mucosa
      circadian dynamics of glutathione (GSH), a sulfhydryl compound, a well-known
      intracellular protective agent. Male Wistar rats, 8-9 weeks of age, were
      maintained at controlled temperature and humidity and 12L:12D day cycle since
      birth. Duodenal mucosa samples obtained by scraping were assayed with a
      spectrophotometric method. The data analysis with the Cosinor method demonstrated
      circadian rhythmicity for GSH content in the duodenal mucosa with higher levels
      during the dark period.

PMID- 10948412
TI  - [Relationship of some environmental factors to disorders in wheat ontogenesis as
      applied to space greenhouse].
AB  - In ground-based experiments reproducing conditions in experiments in the Mir
      greenhouse Svet super dwarf wheat was raised at water potential (WP) in root
      modules with pearlite within the range from -0.5 kPa to -3.0 kPa. At -2.0 kPa the
      number of florets in spikes, mainly the tiller ones, was considerably reduced and
      the actual spikes were fully barren. With WP equal to 0.5 kPa and -1.0 kPa, the
      grain component in the mass of a completely ripe shoot made up 46% and only 32%
      with WP at -2.0 kPa. With WP = 3.0 kPa, spikes of the main shoot and tillers were
      fully barren. In the WP range from 0.5 kPa to 1.0 kPa plants developed two
      tillers and no more than one tiller at 3.0 kPa. In the experiment with elevated
      air temperature mass of tillers at 1.0 kPa was by 39% lower as compared to the
      data from the experiment at the normal temperature. Degenerated anthers and
      abnormal pollen grains were again the cause of full barrenness of spikes grown at
      the normal temperature.

PMID- 10948413
TI  - [Correction of autonomic reactions parameters in organism of cosmonaut with
      adaptive biocontrol method].
AB  - Presented are results of testing the method of adaptive biocontrol during
      preflight training of cosmonauts. Within the MIR-25 crew, a high level of
      controllability of the autonomous reactions was characteristic of Flight
      Commanders MIR-23 and MIR-25 and flight Engineer MIR-23, while Flight Engineer
      MIR-25 displayed a weak intricate dependence of these reactions on the depth of
      relaxation or strain.

PMID- 10948414
TI  - [Correction of arterial pressure parameters].

PMID- 10948415
TI  - [Studies of Russian scientists on the problem of using aviation transport to
      evacuate wounded and patients].

PMID- 10948416
TI  - Estimation of baculovirus titer by beta-galactosidase activity assay of virus
      preparations.

PMID- 10948417
TI  - Detection of clonal B-cell populations using fluorescently labeled nucleotides.

PMID- 10948418
TI  - Sensitive ELISA for mouse erythropoietin.

PMID- 10948419
TI  - Improved procedure for examination of gap junctional intercellular communication
      by in situ electroporation on a partly conductive slide.

PMID- 10948421
TI  - One-step multiplex PCR strategy for identification of mutations by SSCP and DNA
      sequencing.

PMID- 10948420
TI  - Exonuclease III-generated series of homologous competitor DNA fragments for
      competitive PCR.

PMID- 10948422
TI  - RNA amplification technique, NASBA, also amplifies homologous plasmid DNA in non
      denaturing conditions.

PMID- 10948423
TI  - New genetic tools for use in the Rhizobiaceae and other bacteria.

PMID- 10948424
TI  - Pretreatment of microprojectiles to improve the delivery of DNA in plant
      transformation.

PMID- 10948425
TI  - Degradation of persistent RNA in RNase-containing, high-throughput alkaline lysis
      DNA preparations.

PMID- 10948426
TI  - Irreversible heat inactivation of DNase I without RNA degradation.

PMID- 10948427
TI  - Improved cycle sequencing of GC-rich templates by a combination of nucleotide
      analogs.
AB  - A common problem in automated DNA sequencing when applying the Sanger chain
      termination method is ambiguous base calling caused by band compressions. Band
      compressions are caused by anomalies in the migration behavior of certain DNA
      fragments in the polyacrylamide gel because of intramolecular base pairing
      between guanine and cytosine residues. To reduce such undesired secondary
      structures, several modifications of the sequencing reaction parameters have been
      performed previously. Here, we have applied mixtures of the nucleotide analogs 7
      deaza-dGTP and dITP instead of dGTP in the cycle sequencing reaction and in
      combination with varying buffer conditions. Band compressions were particularly
      well resolved, and reading length was optimal when a ratio of 7-deaza-dGTP:dITP
      of 4:1 was used in the in vitro DNA synthesis with AmpliTaq FS DNA polymerase. We
      conclude that the incorporation of both nucleotide analogs at these particular
      ratios leads to heterogeneous DNA chains that result in a reduction or
      elimination of intramolecular base pairing and thus a higher accuracy in the base
      assignment.

PMID- 10948428
TI  - Technique for cloning and sequencing the ends of bacterial artificial chromosome
      inserts.
AB  - Bacterial artificial chromosome (BAC) libraries are an important tool for
      positional cloning, gene analysis and physical mapping. During studies using BAC
      clones, it is often necessary to organize them into contiguous sequences
      (contigs). To finalize, join and extend the contigs, both cloning and sequencing
      of the ends of the inserts are required. Here, we describe a low-cost,
      accessible, fast and powerful method for the routine isolation of BAC ends. This
      method allows the isolation of 20 BAC clone ends in one day. The analysis of the
      ends reveals fragment sizes compatible with sequencing, and the structure of
      these clones allows the sequencing of both ends using the same plasmid. Moreover,
      long end fragments can be sequenced in both directions.

PMID- 10948429
TI  - Streamlined yeast colorimetric reporter activity assays using scanners and plate
      readers.
AB  - Two-hybrid systems have become favored tools for detection and analysis of
      protein interactions because of their low cost and ease of use compared to
      biochemical or biophysical interaction technologies. It is possible to augment
      the utility of two-hybrid systems and derivative systems such as dual-bait two
      hybrid systems by adapting strategies that speed the analysis of the relative
      strength of a series of protein-protein associations. This report describes two
      simple techniques that employ either a flatbed scanner or a plate reader to
      quantitate the activity of colorimetric reporters such as LacZ or GusA commonly
      used in two-hybrid approaches.

PMID- 10948430
TI  - Two-hybrid system for characterization of protein-protein interactions in E.
      coli.
AB  - The yeast two-hybrid system has been used to characterize many protein-protein
      interactions. A two-hybrid system for E. coli was constructed in which one hybrid
      protein bound to a specific DNA site recruits another to an adjacent DNA binding
      site. The first hybrid comprises a test protein, the bait, fused to a chimeric
      protein containing the 434 repressor DNA binding domain. In the second hybrid, a
      second test protein, the prey, is fused downstream of a chimeric protein with the
      DNA binding specificity of the lambda repressor. Reporters were designed to
      express cat and lacZ under the control of a low-affinity lambda operator. At low
      expression levels, lambda repressor hybrids weakly repress the reporter genes. A
      high-affinity operator recognized by 434 repressor was placed nearby, in a
      position that does not yield repression by 434 repressor alone. If the test
      proteins interact, the 434 hybrid bound to the 434 operator stabilizes the
      binding of the lambda repressor hybrid to the lambda operator, causing increased
      repression of the reporter genes. Reconstruction experiments with the fos and jun
      leucine zippers detected protein-protein interactions between either homodimeric
      or heterodimeric leucine zippers.

PMID- 10948431
TI  - Fragment size difference between multiplex and singleplex PCR products and their
      practical implications.
AB  - By simultaneously amplifying several loci in the same reaction, multiplex PCR has
      been used in gene mapping and DNA typing with polymorphic short tandem repeat
      loci. Previous studies have discussed in detail the various parameters and
      conditions that influence the quantity of individual products generated by
      multiplex PCR. In practice, when a primer pair fails to amplify in a multiplex
      PCR for some individuals, singleplex PCR is often employed as a supplement to
      amplify the primer pair. However, the reliability of this procedure is unknown.
      In this study, we used six primer pairs from ABI PRISM Linkage Mapping Set
      version 2 to perform multiplex and singleplex reactions. The fluorescence-labeled
      amplification products were separated and detected on ABI PRISM 310 Genetic
      Analyzer. We found that for the marker D1S468, multiplex and singleplex reactions
      for the majority of individuals yielded reactions of different sizes. Therefore,
      the potential size difference between multiplex and singleplex reactions needs to
      be investigated. This investigation is essential to employ multiplex PCR
      supplemented with singleplex PCR in gene mapping and DNA typing.

PMID- 10948432
TI  - Improved PCR-based subtractive hybridization strategy for cloning differentially
      expressed genes.
AB  - An improved PCR-based subtractive hybridization strategy was used to clone
      apoptosis-related genes induced by all-trans retinoic acid (ATRA) from human
      promyelocytic leukemia cell line HL-60 cells. The protocol used the cap-finder
      method, long-distance PCR, streptavidin magnetic bead-mediated subtraction and
      spin column chromatography. Twenty-seven clones related to apoptosis were
      identified by reverse dot blot assay. Seventeen were known genes, of which seven
      have been reported to be apoptosis related. The remaining 10 were unknown genes,
      five of which were sequenced and named apr-1 to apr-5. apr-1, apr-2, apr-3 and
      TNF were reidentified by reverse dot blot, and it is suggested that they might be
      related to apoptosis. The results suggest that this strategy might be efficient
      for large-scale cloning of differentially expressed genes in target cells.

PMID- 10948433
TI  - Transfer and expression of foreign genes in mammalian cells.
AB  - The transfer of foreign genes into eukaryotic cells, in particular mammalian
      cells, has been essential to our understanding of the functional significance of
      genes and regulatory sequences as well as the development of gene therapy
      strategies. To this end, different mammalian expression vector systems have been
      designed. The choice of a particular expression system depends on the nature and
      purpose of the study and will involve selecting particular parameters of
      expression systems such as the type of promoter/enhancer sequences, the type of
      expression (transient versus stable) and the level of desired expression. In
      addition, the success of the study depends on efficient gene transfer. The
      purification of the expression vectors, as well as the transfer method, affects
      transfection efficiency. Numerous approaches have been developed to facilitate
      the transfer of genes into cells via physical, chemical or viral strategies.
      While these systems have all been effective in vitro they need to be optimized
      for individual cell types and, in particular, for in vivo transfection.

PMID- 10948434
TI  - Control selection for RNA quantitation.
AB  - The study of mammalian gene expression is often carried out at the level of mRNA.
      In such analyses, one usually measures the amount of an mRNA of interest under
      different conditions such as stress, growth, development, cell and tissue
      localization or as part of an evaluation of the effects of gene transfection. A
      variety of techniques exist to measure gene expression and most commonly involve
      Northern hybridization analysis, ribonuclease protection or RT-PCR. Common to all
      of these assays is the inclusion of a so-called loading or internal control
      (i.e., analysis of an mRNA that does not change in relative abundance during the
      course of treatments). Here, we discuss the uses and pitfalls of the most popular
      of these controls, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta
      actin, with special emphasis on precautions associated with the use of GAPDH.

PMID- 10948435
TI  - Automated purification of His6-tagged proteins allows exhaustive screening of
      libraries generated by random mutagenesis.
AB  - In the course of site-directed mutagenesis or directed evolution experiments,
      large numbers of protein variants are often generated. To characterize functional
      properties of individual mutant proteins in vitro, a rapid and reliable protein
      purification system is required. We have developed an automated method for the
      parallel purification of 96 different protein variants that takes about two
      hours. Using a 96-well format, the whole process can be performed automatically
      by a pipetting robot. Coupled with a suitable assay, again using a 96-well
      format, all variants can be functionally characterized within a few hours. The
      protein purification procedure described here is based on the interaction between
      His6-tagged proteins and Ni-NTA-coated microplates. Typical yields are 3-8 pmol
      purified protein/well, which is sufficient to analyze most enzymatic activities.
      Using this procedure, we have purified and characterized variants of the
      restriction endonuclease EcoRV, which were produced in an effort to enhance the
      selectivity of this enzyme. For this purpose, three amino acid residues were
      randomized in a region known from the co-crystal structure to be located at the
      protein-DNA interface. From a library of about 1200 variants, predominantly
      single and double mutants, more than 1000 variants were purified and
      characterized in parallel, which corresponds to an almost complete screening of
      the library.

PMID- 10948437
TI  - Cooperative oligonucleotides in purification of cycle sequencing products.
AB  - Nucleic acid hybridization is an essential component in many of today's standard
      molecular biology techniques. In a recent study, we investigated whether nucleic
      acid capture could be improved by taking advantage of stacking hybridization,
      which refers to the stabilizing effect that exists between oligonucleotides when
      they hybridize in a contiguous tandem fashion. Here, we describe a specific
      approach for purification of sequencing products using cooperative probes that
      hybridize to single-strand targets where one of the probes has been coupled to a
      magnetic bead. This approach has been developed for standard sequencing primers
      and has been applied to shotgun plasmid libraries. The cooperative probes have
      been designed to anneal within the common vector sequence and to avoid co
      purification of nonextended sequencing primers and misprimed sequencing products.
      The reuse of magnetic beads, together with salt independent elution, makes the
      approach suitable for high-capacity capillary electrophoresis instruments.

PMID- 10948436
TI  - Fluorescence polarization for monitoring ribozyme reactions in real time.
AB  - Fluorescence polarization has been used recently to monitor diverse
      macromolecular interactions. In this report, the application of fluorescence
      polarization has been extended to monitor ribozyme reactions in real time. With
      fluorescently labeled substrate RNAs, group I ribozyme ligation and hammerhead
      ribozyme cleavage reactions were studied by fluorescence polarization in
      substrate excess (multiple turnover) conditions. These results also show that
      fluorescently labeled RNAs remain active substrates for ribozymes. Furthermore, a
      direct comparison of fluorescence polarization with fluorescence resonance energy
      transfer showed that both techniques were comparable for monitoring ribozyme
      reactions.

PMID- 10948438
TI  - Development of a semi-quantitative assay to detect full-length CYP2C19 RNA.
AB  - Cytochrome P450 2C19 (CYP2C19) is the enzyme responsible for the metabolism of a
      number of drugs, including anticonvulsants and antidepressants. We have developed
      a semi-quantitative competitive RT-PCR assay to estimate the degree of expression
      of the full-length CYP2C19 message. This assay used a known quantity of
      internally deleted CYP2C19 RNA to quantitate the RT-PCR products of the CYP2C19
      transcript in the RNA extracted from tissues. We determined that this method is
      sensitive and reproducible in assaying for CYP2C19 RNA in human livers. The
      lowest detectable amount of competitor RNA was 0.166 fg or 270 copies of CYP2C19
      competitor RNA. Using human liver samples containing 3-23 x 10(5) copies of
      CYP2C19 RNA, we found the assay to be reproducible with a coefficient of intra-
      and interday variation of 11% and 20%, respectively. Using this assay, we
      measured full-length CYP2C19 RNA in 10 human livers. We found the CYP2C19
      transcripts range from 0.1-23 x 10(5) copies/microgram liver total RNA. The
      analysis of CYP2C19 transcripts for liver of *1 and *2 genotypes, based on
      restriction enzyme digest analysis of RT-PCR products, suggests that only normal
      (*1), not the variant (*2) copy of full-length CYP2C19 RNA, was detectable in
      these livers. We report for the first time the quantification of full-length
      CYP2C19 RNA in livers.

PMID- 10948439
TI  - Managing menopausal problems.

PMID- 10948440
TI  - Sentinel lymphadenectomy in node negative breast cancer.
AB  - SLND, regardless of method, can precisely predict the status of the axillary
      lymph nodes. Despite differences in technique, the consistent results support the
      sentinel node hypothesis in breast cancer. The procedure is well tolerated, and
      staging can be achieved accurately with minimal morbidity. SLND is a minimally
      invasive procedure that provides tissue for the pathologist that represents the
      site most likely to harbor metastases. If a negative sentinel node is removed at
      SLND, it equates to truly node-negative breast cancer in almost all cases when
      done by experienced surgeons familiar with the technique. SLND can be mastered by
      surgeons at several institutions, but requires appropriate training to learn the
      technique. The team involved in SLND, which consists of the surgeon, pathologist
      and nuclear medicine physician, must determine its own false negative rate for
      the procedure, which requires a concomitant ALND so that accuracy is validated.
      Multicenter randomized clinical trials from the American College of Surgeons and
      NSABP are in progress, which will evaluate in general, although with different
      randomization schemes, the outcome of patients who have SLND alone compared to
      those who have ALND. Before ALND is completely abandoned, these trials must be
      completed so that the role of SLND in the management of all patients with early
      breast cancer is fully defined.

PMID- 10948441
TI  - Postmastectomy radiotherapy.

PMID- 10948443
TI  - High-dose chemotherapy for breast cancer.

PMID- 10948442
TI  - The molecular and cellular biology of HER2/neu gene amplification/overexpression
      and the clinical development of herceptin (trastuzumab) therapy for breast
      cancer.

PMID- 10948444
TI  - High dose therapy with stem cell support for breast cancer: the jury is still
      out.

PMID- 10948445
TI  - Preoperative chemotherapy for operable breast cancer.
AB  - In the NSABP B-18 study, it was demonstrated that, in patients with operable
      breast cancer, the administration of preoperative and postoperative chemotherapy
      resulted in similar DFS and overall survival outcomes. In addition, preoperative
      chemotherapy resulted in high clinical response rates but in low rates of
      pathologic response in the breast. Axillary nodal downstaging was convincingly
      demonstrated. In addition, it was also demonstrated in B-18, as well as in other
      studies, that there was an increase in breast conservation rates after the
      administration of preoperative chemotherapy. The role of preoperative
      chemotherapy for operable breast cancer continues to be evaluated in randomized
      trials, which have the potential of providing further insight into the biologic
      and clinical questions relative to the timing of adjuvant therapy for the
      disease.

PMID- 10948446
TI  - Overview of randomized trials of systemic adjuvant therapy.

PMID- 10948447
TI  - Chemoprevention of breast cancer.

PMID- 10948448
TI  - Patterning the early sea urchin embryo.

PMID- 10948449
TI  - Turning mesoderm into blood: the formation of hematopoietic stem cells during
      embryogenesis.
AB  - The formation of hematopoietic stem cells during development occurs by a
      multistep process that begins with the induction of ventral mesoderm. This
      mesoderm is patterned during gastrulation by a bone morphogenetic protein (BMP)
      signaling pathway that is mediated, at least in part, by members of the Mix and
      Vent families of homeobox transcription factors. Following gastrulation, a subset
      of ventral mesoderm is specified to become hematopoietic stem cells. Key
      determinants of hematopoietic fate include the product of the zebrafish cloche
      gene and the basic helix-loop-helix transcription factor SCL. Future studies in
      Xenopus and zebrafish should reveal other critical factors in this developmental
      pathway.

PMID- 10948450
TI  - Mechanisms of plant embryo development.
AB  - 1. Evolution in plants has favored both a simpler body plan with fewer cell types
      and the epigenetic flexibility to regenerate, via growth, dedifferentiation, and
      redifferentiation, to recover from environmental insults. It has become
      increasingly apparent that a plant cell uses external signals to differentiate
      and to maintain or to change the differentiated state. A cell-cell signaling and
      positional information strategy seems to be the predominant mechanism employed in
      plant development. 2. An axis can be initiated by physical/chemical forces such
      as light and ion current, requiring no new gene action. Random chemical
      fluctuations and physicochemical forces could explain the initiation of
      differences among cells of equal developmental potential. Amplification of
      chemical polarizing events may lead to biochemical differences, new gene
      expression, and finally shoot/root axis establishment. 3. Radial and axial
      patterning may be governed by a mechanism involving polar auxin transport. 4.
      Because the meristems and the three fundamental tissues formed during
      embryogenesis are renewed and extended throughout the life of the plant, with
      some exceptions, most genes expressed in the embryo are also expressed during
      postgermination development. 5. Embryogenic competence is acquired during
      reproductive development. While the zygote is determined for embryogenesis, the
      developing embryo and often the seedling remain embryogenic. Embryogenic
      potential declines during vegetative development. The embryogenic strength of a
      tissue is correlated with its developmental distance from the zygote.

PMID- 10948451
TI  - Sperm-mediated gene transfer.

PMID- 10948453
TI  - Attributes and dynamics of the endoplasmic reticulum in mammalian eggs.
AB  - The endoplasmic reticulum is a multifunctional continuous network of membrane
      enclosed sacs and tubules that extends throughout the cell. The endoplasmic
      reticulum is the site of protein synthesis and assembly, as well as lipid and
      membrane synthesis. Additionally, the endoplasmic reticulum contains calcium
      pumps, intraluminal calcium storage proteins, and specific calcium-releasing
      channels. Thus, this membrane system plays a central role in intracellular
      signaling through the storage and release of calcium. At fertilization, the sperm
      triggers a large and dramatic release of calcium from the endoplasmic reticulum,
      which activates the egg to begin development. The ability of the egg to fully
      elevate calcium depends on biochemical and structural changes during oocyte
      maturation. The sensitivity of the calcium-releasing system increases and the
      endoplasmic reticulum is reorganized during maturation of the oocyte; together,
      these dynamic changes place a substantial calcium storage compartment just
      beneath the membrane, near the site of sperm-egg fusion. Localization of the
      calcium store may also contribute to the long-lasting calcium oscillations that
      are characteristic of mammalian fertilization. Examination of the endoplasmic
      reticulum in living eggs is leading to a better understanding of calcium release
      at fertilization.

PMID- 10948452
TI  - Gonocyte-Sertoli cell interactions during development of the neonatal rodent
      testis.
AB  - During neonatal testicular development in the rat, events critical for subsequent
      germ cell development occur that set the stage for fertility later in life. Some
      gonocytes resume mitotic activity and/or migrate to the surrounding basal lamina,
      and use of a carefully defined Sertoli cell-gonocyte coculture system indicates
      that these crucial events occur without added factors or hormones and are hence
      likely to depend on interaction with adjacent Sertoli cells. Coupling of the Kit
      receptor protein on gonocytes to stem cell factor from Sertoli cells is vital for
      successful migration by gonocytes, as antagonism of the former suppresses and
      addition of the latter stimulates gonocyte migration. During the neonatal period,
      intercellular adhesion is modified in a developmental manner such that neural
      cell adhesion molecule (NCAM) is the main adhesive molecule expressed and
      functioning at birth, with a progressive decline as development proceeds. This
      decline in NCAM expression is supported by the addition of exogenous 3,3',5
      triiodothyronine in vitro, and because this factor is recognized as supporting
      Sertoli cell differentiation, it seems likely that changing intercellular
      adhesion is a function of progressive development of Sertoli cells. Other avenues
      whereby maturing testicular cells influence each other doubtless exist, including
      secretion of growth factors and other peptides and developmentally important
      changes in the makeup of the extracellular matrix, which Sertoli cells and
      gonocytes contact. Continued investigation in these areas will be very valuable
      in enlarging our understanding of how neonatal testicular development provides
      the basis for successful spermatogenesis.

PMID- 10948454
TI  - Germ plasm and molecular determinants of germ cell fate.
AB  - One mechanism for the specification of cell types during embryonic development is
      the cytoplasmic localization of determinants in the egg into certain blastomeres.
      Primordial germ cell (PGC) development in many organisms is characterized by the
      inheritance of germ plasm, a cytologically distinct assembly of mitochondria and
      electron-dense germinal granules. This chapter reviews the structure of germ
      plasm and the experimental evidence for its importance in PGC specification in
      Caenorhabditis elegans, Drosophila, and Xenopus. It then compares and contrasts
      recent data on the identification of germ plasm components in these organisms.
      Many components are potentially RNA-binding proteins, implicating the regulation
      of RNA metabolism, transport, and translation as critical processes in PGC
      development. Germ plasm components also mediate transcriptional repression,
      regulate migration, and control mitotic divisions in PGCs. The chapter concludes
      with a discussion on the general roles of germ plasm components and how they
      might act to specify PGC fate.

PMID- 10948455
TI  - Emerging issues in mental retardation: self-determination versus self-interest.

PMID- 10948457
TI  - Long-term care for people with developmental disabilities: a critical analysis.
AB  - This article explores how the trends toward long-term community care affecting
      people with developmental disabilities developed. Appropriateness of care and
      quality of life issues are discussed. The article also reviews the development of
      long-term care for frail and disabled elderly people and explores the arguments
      for a continuum of care that have developed in this area. The authors conclude
      that future policies with respect to meeting long-term care needs for people with
      developmental disabilities must be addressed flexibly on an individual basis,
      related to individual needs, and must provide a continuum of care services.

PMID- 10948456
TI  - Social work early intervention for young children with developmental
      disabilities.
AB  - Social workers' awareness of and formal involvement in family-centered early
      intervention for infants and toddlers who are at risk of or who have
      developmental disabilities has increased considerably during the past 15 years.
      The functional role that social workers can play on early intervention teams and
      as coordinators of early intervention services is underscored by the formal
      recognition of the discipline in the Individuals with Disabilities Education Act.
      Despite the relevance of social work to early intervention, personnel often enter
      early intervention practice without the benefit of formal preparation related to
      very young children with developmental disabilities. This article provides an
      overview of the definition and identification of developmental disabilities, and
      discusses the role of and challenges to social work in early intervention.

PMID- 10948458
TI  - Changes in services and supports for people with developmental disabilities: new
      challenges to established practice.

PMID- 10948459
TI  - Coping strategies, life style changes, and pessimism after open-heart surgery.
AB  - A mail questionnaire was completed by 171 patients two to 20 months after
      undergoing coronary artery bypass graft surgery (CABG). The post-CABG period was
      characterized by fewer working hours, a higher level of physical exercise, a
      reduction in smoking, and more appropriate nutritional habits, compared with the
      preoperation period. At the same time, the anxiety level of post-CABG patients
      was higher than that measured in a community sample. Post-CABG high psychological
      distress (anxiety and mood states) and low functional capacity were associated
      with high levels of pessimism and ineffective emotion-focused coping strategies.
      These results may be used by social workers in devising psychological
      interventions aimed at improving post-CABG patients' quality of life and
      bolstering their coping strategies.

PMID- 10948460
TI  - Qualitative analysis of a BSW field placement with a hospital-owned physician
      practice in a skilled nursing facility.
AB  - Health services and medical social work are being reshaped in the wake of managed
      care and the movement toward community-based delivery systems. In this article, a
      bachelor's of social work student is assigned to a field placement to work with a
      hospital-owned physician practice in a skilled nursing facility. Structured
      interviews are conducted with the field placement student, the physician, a
      resident (client), the field placement instructor, two social work designees, and
      the facility administrator to ascertain the student's practice activities.
      Findings indicate a wide range of duties at both micro- and macro practice
      levels. Value issues and potential considerations for practitioners entertaining
      professional associations with physicians are examined.

PMID- 10948461
TI  - Generational equity and privatization: myth and reality.

PMID- 10948462
TI  - Blastocyst transfer in human in vitro fertilization. A solution to the multiple
      pregnancy epidemic.
AB  - Since the 1950s, the incidence of twin gestation has doubled and the incidence of
      triplets has increased approximately sevenfold in the United States. Of extreme
      concern is the fact that many of these multiple pregnancies are iatrogenic: 35%
      of twin gestations and 77% of higher-order pregnancies are the result of some
      form of infertility therapy. Anything that can be done to reduce the number of
      these multiple pregnancies would benefit our patients and society. Great hope is
      placed on emerging blastocyst technology, which has the potential of achieving
      higher pregnancy rates per embryo transfer while reducing the risk of multiple
      pregnancy. We present the evolution of the blastocyst transfer concept and the
      technical aspects involved. The article also outlines the experience with
      blastocyst culture and transfer at Brigham and Women's Hospital, Boston, and
      describes identifiers for application of blastocyst transfer. The number of eight
      cell embryos on day 3 is an independent marker for the selection of patients who
      would benefit from transfer on day 5. With no eight-cell embryos on day 3, 0% and
      33% pregnancies resulted from day 5 vs. day 3 transfers, suggesting that these
      cases would not benefit from day 5 transfer. When at least one eight-cell embryo
      is available, there is no difference in ongoing pregnancy rates between day 5 and
      day 3 transfers, but there is a significant decrease in multiple gestations with
      day 5 transfers.

PMID- 10948463
TI  - Transvaginal bladder neck suspension with Cooper's ligament fixation. Long-term
      urodynamic results.
AB  - OBJECTIVE: To evaluate the long-term urodynamic efficacy of transvaginal bladder
      neck suspension with Cooper's ligament fixation. STUDY DESIGN: Nineteen women
      underwent transvaginal bladder neck suspension with Cooper's ligament fixation.
      Patients underwent complete clinical and urodynamic testing before and four to
      five years after surgery. Cure was defined as absence of urine leakage with
      stress maneuvers at cystometric capacity and lack of symptoms of urine loss.
      RESULTS: A successful outcome was documented in 12/14 patients. One patient
      developed de novo detrusor instability, and two had stress incontinence. Five
      were lost to long-term follow-up. CONCLUSION: Transvaginal bladder neck
      suspension with Cooper's ligament fixation is an effective surgical option in the
      treatment of genuine stress incontinence.

PMID- 10948464
TI  - Improving preconception care.
AB  - OBJECTIVE: To improve the documentation and delivery of preconception care to all
      women of reproductive age attending an inner city hospital's outpatient
      gynecology clinic. A secondary goal was to evaluate the knowledge and awareness
      of providers regarding preconception care. STUDY DESIGN: A preintervention chart
      review of a convenience sample of non-pregnant women with reproductive potential
      who attend an inner city hospital gynecology clinic (n = 100) was conducted to
      evaluate delivery of preconception care. Items screened for included: family
      planning services, domestic violence, nutrition and medical risk factors,
      medication use, appropriate counseling and use of referral services. All
      providers in the clinic were surveyed to assess their knowledge of and attitudes
      toward preconception care. A two-part intervention was then carried out: (1) a
      one-hour lecture for all providers, and (2) a standardized preconception care
      form inserted in all charts. A postintervention chart review of a second
      convenience sample (n = 100) and repeat provider survey were then conducted to
      evaluate the effectiveness of the two interventions. RESULTS: Following the two
      pronged intervention, there was evidence of improved documentation of the
      delivery of preconception care. Documentation of screening in almost all
      categories was significantly improved (P < .05). The greatest improvements were
      noted in complete screening for medical risk factors (from 15% to 44%), for over
      the-counter and prescription medication use (from 10% to 70% and 30% to 77%,
      respectively), domestic violence (from 10% to 57%) and nutrition (from 9% to
      50%). However, provider knowledge of and attitudes toward preconception care were
      not significantly changed. CONCLUSION: The combination of education about
      preconception care and insertion of a standardized form into a patient's chart
      led to a clear improvement in the documentation of preconception care. Given the
      significance of preconception care, insertion of a standardized form should be
      considered to help providers complete and appropriate care to their patients.

PMID- 10948465
TI  - Postablative risk of endometrial carcinoma in New Zealand white rabbits given
      high-dose estrogen.
AB  - OBJECTIVE: To follow a population at high risk for endometrial carcinoma after
      endometrial ablation, to determine if ablation alters the incidence or detection
      of endometrial pathology. STUDY DESIGN: The animal model included 33 New Zealand
      white rabbits. Of this cohort, 17 underwent surgical ablation of the endometrium
      via laparotomy, while 16 served as controls. Vaginal bleeding was assessed with
      monthly cotton swab examinations as well as daily observation of the subjects.
      All animals received unopposed estrogen for 18 months prior to necropsy. RESULTS:
      No animal in either arm of the study demonstrated vaginal bleeding. Two rabbits
      from the ablation group and three controls showed histologic evidence of atypical
      endometrial hyperplasia or adenocarcinoma (P > .20). One additional animal from
      each group had hyperplasia without atypia. CONCLUSION: This animal model suggests
      that endometrial ablation does not decrease the risk of endometrial carcinoma in
      patients at high risk of developing endometrial pathology. Detection of
      hyperplasia or carcinoma in such a population may prove difficult due to the
      absence of traditional signs of endometrial abnormalities.

PMID- 10948466
TI  - Effect of epidural analgesia on the primary cesarean section and forceps delivery
      rates.
AB  - OBJECTIVE: To determine the impact of introducing epidural analgesia for labor
      pain relief on the primary cesarean and forceps delivery rates. STUDY DESIGN: The
      control group consisted of 1,720 women who delivered on a charity hospital
      service between September 1, 1992, and August 31, 1993; epidural analgesia was
      not available for this cohort of patients. The study group consisted of 1,442
      patients who delivered on the same service between September 1, 1993, and August
      31, 1994; elective epidural analgesia for labor pain relief was available for
      this cohort of patients. A computerized obstetric database was analyzed to
      compare the two groups regarding demographics, parity, pregnancy complications,
      labor characteristics, type of delivery, low birth weight incidence and five
      minute Apgar scores. RESULTS: The two groups were similar with respect to
      demographics and pregnancy complications. No control group patient received
      epidural analgesia for labor pain relief; 734 of 1,285 (57%) laboring patients in
      the study group elected epidural analgesia for pain relief. The primary cesarean
      delivery rate for the control group was 9.6% and for the study group 11.0% (not
      statistically significant). The control group had 34 (2.0%) forceps deliveries
      and the study group, 88 (6.1%), for a statistically significant difference. There
      were significantly more vaginal births after cesarean in the study group (42 vs.
      26). CONCLUSION: Epidural analgesia was not associated with an increase in the
      primary cesarean delivery rate but was associated with an increase in the
      operative vaginal delivery rate.

PMID- 10948467
TI  - Umbilical artery Doppler velocimetry in pregnancies complicated by
      oligohydramnios.
AB  - OBJECTIVE: To determine the role of umbilical artery Doppler velocimetry in the
      management of oligohydramnios. STUDY DESIGN: In a retrospective chart review
      covering a two-year period, pregnancies with oligohydramnios evaluated by Doppler
      velocimetry of the umbilical artery were identified. Those patients with ruptured
      membranes and complex congenital anomalies were excluded from analysis. In the
      remainder, various measures of perinatal morbidity, including delivery of a small
      for-gestational-age infant, preterm delivery, hyperbilirubinemia, requirement for
      blood transfusion, and other cardiovascular or pulmonary complications, were
      correlated with recorded values of the systolic/diastolic (S/D) ratio. RESULTS:
      Seventy-six subjects were identified for study. Forty-six had normal S/D ratios;
      17 (37%) were associated with identifiable perinatal morbidity. When prematurity
      due to delivery for the sole indication of oligohydramnios was excluded,
      morbidity occurred in five patients (11%). Conversely, of the 30 patients with
      abnormal Doppler indices, 80% had an adverse outcome. CONCLUSION: Pregnancies
      with oligohydramnios and normal umbilical artery Doppler velocimetry were
      significantly (P < .001) less likely to experience an abnormal perinatal outcome
      as compared to those with abnormal Doppler indices. An elevated S/D ratio
      identified an increased risk of an adverse perinatal outcome in women with
      oligohydramnios. Avoiding intervention in pregnancies with oligohydramnios and
      normal umbilical artery Doppler velocimetry may decrease iatrogenic morbidity due
      to prematurity by as much as 26%.

PMID- 10948468
TI  - Lymphocyte subpopulations after normal pregnancy and spontaneous abortion in
      primigravidas.
AB  - OBJECTIVE: To evaluate lymphocyte subpopulations after a first pregnancy in women
      who had normal pregnancies and in those whose pregnancies terminated in
      spontaneous abortion. STUDY DESIGN: Sixty healthy, nonpregnant women in three
      groups were studied: 20 with a prior abortion, 20 with a prior normal pregnancy
      and 20 nulligravid. Peripheral blood lymphocytes were studied using monoclonal
      antibodies and flow cytometry. Women were followed for one year, and if they
      became pregnant again, pregnancy complications were recorded. RESULTS: The
      percentage of B lymphocytes was significantly decreased in the postpartum group
      (6% +/- 2.22) in comparison to nulligravid women (8.7% +/- 3.37) (P = .005). The
      percentage of CD4 lymphocytes was significantly higher in the postabortion group
      (44.7% +/- 7.81) in relation to the control group (39.85% +/- 6.01) (P = .03). A
      significantly higher CD4/CD8 ratio was found in the postabortion group in
      relation to the control group (1.65 vs. 1.24) (P = .01). Women with pregnancy
      complications in their next pregnancy had a lower absolute value for total
      lymphocytes (P = .02), T lymphocytes (P = .04), absolute CD8 lymphocytes (P =
      .01) and percentage of CD8 lymphocytes (P = .02) and a higher percentage of CD4
      lymphocytes (P = .03) and higher CD4/CD8 ratio (P = .02) than women who had not
      experienced any pregnancy complications. CONCLUSION: The percentage of B
      lymphocytes was lower in normal primipara in comparison to women who had never
      been pregnant. Women with previous spontaneous abortions had an immunologic
      profile expected in a rejection phenomenon; that result was more marked if they
      went on to experience complications in their next pregnancies.

PMID- 10948469
TI  - Conservative management of isolated posthysterectomy fever.
AB  - OBJECTIVE: To demonstrate that an isolated fever in the absence of other signs or
      symptoms of infection following hysterectomy does not require empiric antibiotics
      and laboratory tests. METHODS: Retrospective analysis of all the charts of
      patients who had a hysterectomy from July 1995 to December 1996 at our
      institution. Patients with a postoperative temperature > 38 degrees C had a
      physical examination. If the examination was normal, no studies were ordered, and
      antibiotic therapy was not initiated. If a patient was febrile after 72 hours
      postoperatively, laboratory studies and radiographic tests were ordered. If the
      results were negative, the patient did not appear septic, and physical
      examination was normal, no antibiotics were given. Outcomes were measured by
      comparing patients with postoperative infections and fever to those without
      infections. RESULTS: Of 132 patients, 112 were included in the study. Seventy-two
      hysterectomies were abdominal and 40 vaginal. Postoperative fever during the
      first 72 hours following hysterectomy occurred in 51/112 (46%) patients.
      Clinically significant infection was documented in seven patients, all of whom
      manifested signs and symptoms of infection > 72 hours postoperatively.
      CONCLUSION: Postoperative fever in the first 72 hours after hysterectomy is
      common and nonspecific. If a febrile patient does not show any other signs or
      symptoms of infection, it is safe to forego routine laboratory and imaging
      studies as well as therapeutic antibiotics.

PMID- 10948470
TI  - Intracavitary radiotherapy for refractory dysfunctional uterine bleeding. A case
      report.
AB  - BACKGROUND: Pelvic irradiation was once a common treatment for dysfunctional
      uterine bleeding (DUB). Today the majority of women with DUB are successfully
      treated with hormonal therapy; patients unresponsive to hormonal therapy may
      require endometrial ablation or hysterectomy. We present a patient with severe,
      intractable DUB and contraindications to surgery who was treated with
      intracavitary radiotherapy. CASE: A 39-year-old, 150-cm-tall, 310-kg woman was
      referred for management of severe DUB refractory to medical management. The
      bleeding was successfully treated with intracavitary cesium. Hysterectomy was not
      recommended due to the operative risks posed by the patient's massive obesity.
      Because of technical difficulties during a previous dilation and curettage and
      the expense of long-term GnRH agonist therapy, the patient elected to undergo
      intracavitary radiotherapy. CONCLUSION: In selected patients, intracavitary
      radiotherapy can be used to treat DUB when conventional therapy fails or is
      contraindicated.

PMID- 10948471
TI  - Mycobacterium chelonae sepsis associated with long-term use of an intravenous
      catheter for treatment of hyperemesis gravidarum. A case report.
AB  - BACKGROUND: Of the 1-2% of pregnant women who develop hyperemesis, the great
      majority are managed successfully with antiemetics and, when needed, short
      courses of parenteral medications. Only rarely will chronic parenteral therapy be
      necessary. Such therapy may be associated with significant complications. CASE: A
      38-year-old woman, gravida 3, para 1, induced abortion 1, with a history of
      hyperemesis in her first pregnancy, developed recurrent hyperemesis at 9 weeks'
      gestation. After four admissions and a 5.45-kg weight loss at 12 weeks'
      gestation, a Groshong catheter was placed in the left subclavian vein. The
      patient was then managed with home droperidol infusions and intravenous hydration
      as needed. At 30 weeks' gestation she developed tender, erythematous nodules over
      her legs and right arm. Culture from a biopsy of the nodules grew Mycobacterium
      chelonae, as did the catheter tip. M chelonae is a ubiquitous, opportunistic,
      nontuberculous (atypical) mycobacterium. The patient responded slowly to
      clarithromycin. At 37 weeks she delivered a healthy, 4,080-g, male infant. Three
      months postpartum the nodules continued to resolve slowly on clarithromycin.
      CONCLUSION: When chronic parenteral therapy is required for hyperemesis
      gravidarum, attention must be given to potential complications. Indwelling
      catheters should be removed as soon as possible.

PMID- 10948472
TI  - Neurosarcoidosis diagnosed during pregnancy by thoracoscopic lymph node biopsy. A
      case report.
AB  - BACKGROUND: Sarcoidosis is a multiorgan-system granulomatous disease causing
      respiratory complaints in most patients. Eye involvement, most commonly
      granulomatous uveitis, is seen in 5% of black patients with sarcoidosis.
      Neurosarcoidosis is also rare, affecting 5% of patients with sarcoidosis.
      Thoracoscopic lymph node biopsy in pregnancy has never before been reported.
      CASE: An otherwise-healthy, 25-year-old woman, gravida 2, para 1001, presented at
      25 weeks' gestation with a painful facial palsy and visual defects.
      Ophthalmologic examination revealed uveitis, and a chest radiograph revealed
      asymmetric hilar adenopathy. At 28 weeks' gestation, the patient underwent
      thoracoscopic lymph node biopsy, which confirmed the diagnosis of sarcoidosis.
      The symptoms were stabilized with therapeutic corticosteroids, and the patient
      delivered a healthy neonate at term. CONCLUSION: The diagnosis of sarcoidosis
      remains one of exclusion and requires a high index of suspicion. Tissue
      confirmation is often necessary, especially when patients have extrathoracic
      complaints. For patients without other lesions amenable to biopsy, thoracoscopic
      lymph node biopsy can be considered despite pregnancy.

PMID- 10948473
TI  - Prenatal diagnosis of congenital hypophosphatasia in a consanguineous Bedouin
      couple. A case report.
AB  - BACKGROUND: Hypophosphatasia is a rare autosomal recessive metabolic disorder
      characterized by low serum and tissue alkaline phosphatase activity, increased
      urinary excretion of phosphoethanolamine and ricketslike changes in the bone.
      CASE: We present a case of prenatal diagnosis of congenital hypophosphatasia in a
      consanguineous Bedouin couple. The case was diagnosed at 24.5 weeks of gestation.
      Sonographic evaluation revealed a fetus with short and deformed bones and a
      hypoechogenic skull. Based on the sonographic findings and the obstetric history
      of the couple, hypophosphatasia was diagnosed. The parents opted for pregnancy
      termination. Feticide was accomplished uneventfully. Laboratory findings
      confirmed the diagnosis. CONCLUSION: This couple was prone to this metabolic
      disorder due to their consanguineous marriage and previous affected fetus. Early
      first-trimester prenatal diagnosis by first-trimester chorionic villus sampling
      or second-trimester measuring of alkaline phosphatase activity in the amniotic
      fluid is required to exclude this lethal disease in subsequent pregnancies.

PMID- 10948474
TI  - Breakpoint of a Y chromosome pericentric inversion in the DAZ gene area. A case
      report.
AB  - BACKGROUND: The presence of a spermatogenesis locus (gene or gene complex) in the
      euchromatic region of the long arm of the Y chromosome (Yq11), defined as
      azoospermia factor on the basis of gross structural rearrangement, was detected.
      The gene family responsible for different spermatogenetic defects is "deleted in
      azoospermia" (DAZ). CASE: A 34-year-old man had oligozoospermia, and a
      cytogenetic analysis carried out on peripheral lymphocytes with G banding
      revealed a 46,X, inv(Y)(p11q11)karyotype. The relation between the chromosomal
      breakpoint and the DAZ gene was more precisely defined by a fluorescent in situ
      hybridization technique. We revealed two signals for the DAZ gene, weaker than
      normal, one on the short arm and the other on the long arm of the Y chromosome,
      indicating that the breakpoint was located at the DAZ gene level. CONCLUSION:
      This is the first report documenting a chromosomal pericentric inversion with
      disruption in the DAZ gene area. We hope to obtain information on whether the
      disruption affects a functional zone of the gene and correlates with oligospermia
      at the chromosomal level.

PMID- 10948475
TI  - Alternative conservative management of placenta accreta. A case report.
AB  - BACKGROUND: Placenta accreta is a rare event in pregnancy and may cause life
      threatening hemorrhage. This obstetric complication is a diagnostic and
      management challenge. When the condition is diagnosed, medical management is
      usually employed first for hemostasis. If the bleeding cannot be controlled,
      conservative surgical management is attempted, but hysterectomy is often required
      for definitive care. CASE: The diagnosis of placenta accreta was made
      intraoperatively at cesarean section undertaken for breech presentation. The
      placenta was densely adherent to the anterior lower uterus. Severe hemorrhage,
      which resulted from attempts to manually remove it, was treated with oxytocin,
      carboprost tromethamine and methylergonovine without success. The uterus was
      everted to provide access to the placental site, which was excised; the
      myometrial defect was sutured closed. Three Foley balloons were used to provide
      uterine tamponade. Methotrexate was administered prophylactically. These measures
      effectively controlled the hemorrhage. CONCLUSION: Because placenta accreta might
      not be diagnosed antepartum or during labor, especially when no risk factors are
      present, adequate preparations cannot be made. If it is diagnosed at the time of
      cesarean section, a combined conservative approach may prove helpful in
      controlling bleeding and avoid hysterectomy and hypovolemia.

PMID- 10948476
TI  - Laparoscopic removal of a rudimentary uterine horn during pregnancy. A case
      report.
AB  - BACKGROUND: A unicornuate uterus with a rudimentary horn is a mullerian anomaly
      associated with endometriosis and pregnancy complications, including miscarriage,
      ectopic pregnancy, uterine rupture, preterm labor and malpresentation. Therefore,
      the horn is removed if it is thought to contain functional endometrium. This is
      usually done by laparotomy in the nonpregnant state. CASE: A woman presented
      during pregnancy with symptoms, examination and ultrasonogram suspicious for an
      ectopic pregnancy. Intraoperative findings and final pathology, however, showed a
      rudimentary uterine horn, which was laparoscopically removed, and a concomitant
      intrauterine pregnancy. CONCLUSION: A rudimentary uterine horn may present during
      pregnancy and mimic an ectopic pregnancy. In this case, the horn was removed
      laparoscopically.

PMID- 10948477
TI  - Isolated cardiac metastasis of cervical carcinoma presenting as disseminated
      intravascular coagulopathy. A case report.
AB  - BACKGROUND: An isolated cardiac metastasis from cervical carcinoma is very rare.
      This report describes the unusual presentation in a patient diagnosed and
      successfully treated for stage IB squamous cell carcinoma of the cervix,
      presenting six months later with disease metastatic to the heart. CASE: A 44-year
      old woman presented with hand swelling and bruising. She had undergone successful
      surgical treatment of a stage IB squamous cell cervical carcinoma six months
      previously. Computed tomography revealed a large mass in the right ventricle,
      confirmed by echocardiography. The patient underwent surgery, where the mass was
      biopsied and debulked under a cardiopulmonary bypass. Frozen section confirmed
      metastatic squamous cell carcinoma. The patient was discharged with follow-up
      radiation and chemotherapy. CONCLUSION: All women with myocardial abnormalities
      and a history of squamous cell carcinoma of the cervix should be suspected of
      developing a myocardial metastasis until proven otherwise.

PMID- 10948478
TI  - Shoulder dystocia.

PMID- 10948480
TI  - Assault, PTSD, family substance use, and depression as risk factors for cigarette
      use in youth: findings from the National Survey of Adolescents.
AB  - A national household probability sample of 4,023 adolescents aged 12 to 17 years
      was surveyed by telephone via structured clinical interview to determine the
      impact of familial substance use, sexual and physical assault, witnessed
      violence, depression and posttraumatic stress disorder (PTSD) on risk of smoking.
      Results indicated that familial substance use increased risk of smoking only for
      boys and sexual assault or depression increased risk of smoking only for girls.
      Age, Caucasian ethnicity, and experiencing physical assault or witnessing
      violence elevated risk of current cigarette use for both genders. By contrast,
      PTSD per se was not associated with increased risk of smoking, after the effects
      of other variables were controlled.

PMID- 10948479
TI  - The Children's PTSD Inventory: development and reliability.
AB  - Information involving the development of the DSM-IV version of the Children's
      PTSD Inventory is described. Independent ratings by highly experienced judges
      denote that the instrument encompassed the universe of definition that it was
      intended to measure (i.e., the DSM-IV criteria for PTSD). The instrument was
      administered to 82 traumatized and 22 nontraumatized youths at Bellevue Hospital.
      Moderate to high Cronbach alphas (.53-.89) were evident at the subtest level. An
      alpha of .95 was evident at the diagnostic level. In terms of inter-rater
      reliability, 98.1% agreement was evident at the diagnostic level. Inter-rater
      intraclass correlation coefficients (ICCs) ranged from .88 to .96 at the subtest
      level and .98 at the diagnostic level. Good to excellent kappas (.66-1.00) were
      reported for inter-rater reliability at the subtest level. An inter-rater
      reliability kappa of .96 was evident at the diagnostic level. In terms of test
      retest reliability, 97.6% agreement was evident at the diagnostic level. Good to
      excellent test-retest kappas (.66-1.00) and ICCs (.66-.94) were observed. A test
      retest kappa of .91 and an ICC of .88 was observed at the diagnostic level.

PMID- 10948481
TI  - An evaluation of stress symptoms associated with academic sexual harassment.
AB  - It is clear that sexual assault can precipitate posttraumatic stress disorder.
      Some theorists have suggested that less severe sexually harassing behaviors may
      also have trauma-like sequelae. In a study evaluating this hypothesis, 69 female
      participants completed self-report measures of instances of sexual harassment,
      basic beliefs, psychological distress/symptoms, and PTSD symptoms. Participants
      watched videotapes depicting sexual harassment, emotional arousal (not sexual in
      nature), and a neutral interaction while their heart rate was monitored, and they
      were interviewed using the SCID for PTSD. Results revealed that those who had
      been sexually harassed reported more negative basic beliefs, more general
      distress, and more negative state mood after watching the sexual harassment
      video, relative to those who had not been harassed. The severity of sexual
      harassing behaviors experienced was positively correlated with PTSD symptoms.
      Heart rate reactivity to the videotapes did not differ across groups defined by
      sexual harassment status.

PMID- 10948482
TI  - Refugee families' experience of research participation.
AB  - Because refugees can experience crisis, bereavement, and traumatization, there
      has been a rapid increase of research carried out with refugees. This study
      investigated how refugee families respond to participation in research. A
      previous study explored how adults and children had communicated about the
      difficult question of repatriation after arriving in a new country. Did the in
      depth interviews harm or benefit them? Are there any ethical risks in research on
      traumatized refugees? From an original sample of 74 Bosnian refugees (5-73
      years), 30 family members from 9 families including 14 children aged 6 to 19,
      were re-interviewed. The refugees rated participation as positive. A few parents
      lacked information that could have enabled them to inform the children better
      before the interviews. The study shows that studies on traumatized/bereaved
      populations can have beneficial effects.

PMID- 10948483
TI  - Posttraumatic stress disorder symptoms in Korean conflict and World War II combat
      veterans seeking outpatient treatment.
AB  - Given important differences in the Korean conflict and World War II, samples of
      treatment-seeking combat veterans from these wars (30 Korea, 83 World War II)
      were compared on the prevalence and severity of posttraumatic stress disorder
      (PTSD). With age, ethnicity, and combat exposure taken into account, the Korean
      veterans reported significantly more severe symptoms on both interview and self
      report PTSD measures. Group differences in the prevalence of current PTSD were in
      a similar direction but not significant. These results are generally consistent
      with other studies that have found Korean combat veterans to exhibit higher rates
      of psychosocial maladjustment than World War II combat veterans. Based on related
      research with Vietnam veterans, one direction for future investigation is to
      examine what role stressful postmilitary homecoming experiences may have played
      in influencing the development and course of combat-related PTSD in the aging
      cohort of "forgotten" Korean conflict veterans.

PMID- 10948484
TI  - Head injury as a predictor of psychological outcome in combat veterans.
AB  - Although it is recognized that psychosocial variables influence the expression of
      psychopathology following trauma exposure, physiological variables have received
      less attention as potential mediators of psychological outcome in trauma victims.
      The purpose of this study was to examine the relationship of head injury to
      psychological outcome in 171 combat veterans seeking compensation for service
      connected disabilities for mental disorders attributed to etiologies other than
      head injury. Veterans underwent structured psychiatric diagnostic interview and
      completed self-report measures of combat exposure, posttraumatic stress disorder
      (PTSD), depression, and occurrence of head injury. Comparisons between veterans
      with and without history of head injury indicated that head injury was associated
      with more severe depression. Regression analysis suggested that head injury
      predicted depression, but not PTSD, severity.

PMID- 10948485
TI  - Nocturnal re-experiencing more than forty years after war trauma.
AB  - The aim of this study was the examination of Posttraumatic Nightmares (PTNM) and
      Posttraumatic Anxiety Dreams (PTAD) in Dutch combat veterans and World War II
      victims. Participants (outpatients; n = 223) were administered a standardized
      psychiatric interview, the Impact of Event Scale, the SCL-90, the Clinician
      Administered PTSD Scale, and an interview on posttraumatic nocturnal re
      experiencing. Prevalence of PTNM was 56%. Patients with PTNM, even those who were
      not diagnosed with PTSD, had significantly more psychiatric complaints than
      patients with no PTNM. Analysis of PTNM demonstrated that they were often
      experienced as exact replications of the original traumatic events. Replicative
      PTNM often implicated dream recurrence. Traumatic experiences before the age of 5
      resulted in nonreplicative PTNM only. Unlike nonreplicative PTNM, replicative
      PTNM seemed to be correlated with several intrusion subscales.

PMID- 10948486
TI  - Distress experienced by participants during an epidemiological survey of
      posttraumatic stress disorder.
AB  - We examined the potential for epidemiological studies of mental disorders,
      specifically of posttraumatic stress disorder (PTSD), to cause further harm to
      participants involved. Of 1,000 randomly selected Australian Vietnam veterans,
      641 agreed to participate in an epidemiological survey. Participants were asked
      about distress experienced during the interview when traumatic events were
      raised. Significant distress attributed to the interview was reported by 75.3% of
      those with current PTSD, 56.5% of those with past PTSD, and 20.6% of those with
      no PTSD diagnosis. Distress did not affect participants' use of medical services
      following the interview nor did it affect their willingness to continue
      participating in the study. We concluded that research interviews about PTSD may
      cause short-term distress, but found no evidence of long-term harm.

PMID- 10948487
TI  - The effects of extreme early stress in very old age.
AB  - This article examines a community-based sample of Holocaust survivors aged 75 and
      over, in comparison to persons of similar age and sociocultural background who
      did not personally experience the Holocaust. The analysis compares respondents'
      sociodemographic characteristics, interpersonal resources (locus of control and
      social network), and vulnerability, stratified by gender (n = 194). Assessments
      of vulnerability (physical health, mental health, and posttraumatic stress
      disorder--PTSD) are compared across groups. The results reveal almost no
      differences regarding the sociodemographic and interpersonal variables.
      Nevertheless, survivors are found to be more vulnerable than the others in the
      comparison group: (a) male survivors demonstrate a higher prevalence of PTSD, and
      (b) female survivors indicate greater health-related difficulties and poorer self
      rated health.

PMID- 10948488
TI  - Exploring the roles of emotional numbing, depression, and dissociation in PTSD.
AB  - Some researchers consider emotional numbing a cardinal feature of posttraumatic
      stress disorder (PTSD). Others view numbing symptoms as representing an overlap
      between PTSD, depression, and dissociation. In this study, we examined the
      ability of early emotional numbing, depression, and dissociation symptoms to
      predict PTSD. One-hundred sixty-one women who were recent victims of sexual or
      nonsexual assault were assessed prospectively for 12 weeks. Emotional numbing,
      depression, and dissociation were each associated with initial PTSD severity.
      Notably, regression analyses revealed that after depression and dissociation were
      accounted for, early numbing contributed to the prediction of later PTSD.

PMID- 10948489
TI  - Fear, helplessness, and horror in posttraumatic stress disorder: investigating
      DSM-IV criterion A2 in victims of violent crime.
AB  - A DSM-IV diagnosis of posttraumatic stress disorder (PTSD) required for the first
      time that individuals must report experiencing intense fear, helplessness, or
      horror at the time of the trauma. In a longitudinal study of 138 victims of
      violent crime, we investigated whether reports of intense trauma-related emotions
      characterized individuals who, after 6 months, met criteria for PTSD according to
      the DSM-III-R. We found that intense levels of all 3 emotions strongly predicted
      later PTSD. However, a small number of those who later met DSM-III-R or ICD
      criteria for PTSD did not report intense emotions at the time of the trauma. They
      did, however, report high levels of either anger with others or shame.

PMID- 10948490
TI  - Behavioral treatment of PTSD in a perpetrator of manslaughter: a single case
      study.
AB  - Studies of posttraumatic stress disorder (PTSD) have predominantly focused on
      victims of trauma. Some studies have examined the after-effects of a person's own
      violent actions in combat or police situations. However, there is a sparsity of
      literature examining the development of PTSD in convicted perpetrators of violent
      crime, and there is no literature concerning the treatment of PTSD in such
      perpetrators. This single-case study presents the outcome of behavioral treatment
      in one case in which the patient had PTSD consequential to being a perpetrator of
      manslaughter. The theoretical implications of this case are briefly discussed.

PMID- 10948491
TI  - A correlational test of the relationship between posttraumatic growth, religion,
      and cognitive processing.
AB  - The present study examined the degree to which event related rumination, a quest
      orientation to religion, and religious involvement is related to posttraumatic
      growth. Fifty-four young adults, selected based on prescreening for experience of
      a traumatic event, completed a measure of event related ruminations, the Quest
      Scale, an index of religious participation, and the Posttraumatic Growth
      Inventory. The three subscales of the Quest Scale, the two groups of rumination
      items (soon after event/within past two weeks), and the index of religious
      participation were entered in a standard multiple regression with the total score
      of the Posttraumatic Growth Inventory as the dependent variable. The degree of
      rumination soon after the event and the degree of openness to religious change
      were significantly related to Posttraumatic Growth. Congruent with theoretical
      predictions, more rumination soon after the event, and greater openness to
      religious change were related to more posttraumatic growth. Present findings
      offer some confirmation of theoretical predictions, and also offer clear
      direction for further research on the relationships of religion, rumination, and
      posttraumatic growth.

PMID- 10948492
TI  - Ataque de nervios and history of childhood trauma.
AB  - OBJECTIVE: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis.
      It typically describes episodic, dramatic outbursts of negative emotion in
      response to a stressor, sometimes involving destructive behavior. Dissociation
      and affective dysregulation during such episodes suggested a link to childhood
      trauma. We therefore assessed psychiatric diagnoses, history of ataque, and
      childhood trauma in treatment-seeking Hispanic outpatients (N = 70).
      Significantly more subjects with an anxiety or affective disorder plus ataque
      reported a history of physical abuse, sexual abuse, and/or or a substance-abusing
      caretaker than those with psychiatric disorder but no ataque. In some Hispanic
      individuals, ataque may represent a culturally sanctioned expression of extreme
      affect dysregulation associated with childhood trauma. Patients with ataque de
      nervios should receive a thorough traumatic history assessment.

PMID- 10948494
TI  - Direct analysis of proteins in mixtures. Application to protein complexes.

PMID- 10948493
TI  - De Novo peptide sequencing by nanoelectrospray tandem mass spectrometry using
      triple quadrupole and quadrupole/time-of-flight instruments.

PMID- 10948495
TI  - Characterization of a mutant recombinant S100 protein using electrospray
      ionization mass spectrometry.

PMID- 10948496
TI  - Searching sequence databases via de novo peptide sequencing by tandem mass
      spectrometry.

PMID- 10948497
TI  - Signature peptides. From analytical chemistry to functional genomics.

PMID- 10948498
TI  - Investigating the higher order structure of proteins. Hydrogen exchange,
      proteolytic fragmentation, and mass spectrometry.

PMID- 10948499
TI  - Probing protein surface topology by chemical surface labeling, crosslinking, and
      mass spectrometry.

PMID- 10948500
TI  - Secondary structure of peptide ions in the gas phase evaluated by MIKE
      spectrometry. Relevance to native conformations.

PMID- 10948501
TI  - Preparation and mass spectrometric analysis of S-nitrosohemoglobin.

PMID- 10948502
TI  - Multiple and subsequent MALDI-MS on-target chemical reactions for the
      characterization of disulfide bonds and primary structures of proteins.

PMID- 10948503
TI  - Epitope mapping by a combination of epitope excision and MALDI-MS.

PMID- 10948504
TI  - Identification of active site residues in glycosidases by use of tandem mass
      spectrometry.

PMID- 10948505
TI  - Probing protein-protein interactions with mass spectrometry.

PMID- 10948506
TI  - Studies of noncovalent complexes in an electrospray ionization/time-of-flight
      mass spectrometer.

PMID- 10948507
TI  - Kinetic analysis of enzymatic and nonenzymatic degradation of peptides by MALDI
      TOFMS.

PMID- 10948508
TI  - Characterization of protein glycosylation by MALDI-TOFMS.

PMID- 10948509
TI  - Positive and negative labeling of human proinsulin, insulin, and C-peptide with
      stable isotopes. New tools for in vivo pharmacokinetic and metabolic studies.

PMID- 10948510
TI  - Identification of snake species by toxin mass fingerprinting of their venoms.

PMID- 10948511
TI  - Mass spectrometric characterization of the beta-subunit of human chorionic
      gonadotropin.

PMID- 10948512
TI  - Analysis of gluten in foods by MALDI-TOFMS.

PMID- 10948513
TI  - Quantitation of nucleotidyl cyclase and cyclic nucleotide-sensitive protein
      kinase activities by fast-atom bombardment mass spectrometry. A paradigm for
      multiple component monitoring in enzyme incubations by quantitative mass
      spectrometry.

PMID- 10948514
TI  - Influence of salts, buffers, detergents, solvents, and matrices on MALDI-MS
      protein analysis in complex mixtures.

PMID- 10948515
TI  - Sample preparation techniques for peptides and proteins analyzed by MALDI-MS.

PMID- 10948516
TI  - Analysis of hydrophobic proteins and peptides by mass spectrometry.

PMID- 10948517
TI  - Analysis of proteins and peptides directly from biological fluids by
      immunoprecipitation/mass spectrometry.

PMID- 10948518
TI  - Detection of molecular determinants in complex biological systems using MALDI-TOF
      affinity mass spectrometry.

PMID- 10948519
TI  - Rapid identification of bacteria based on spectral patterns using MALDI-TOFMS.

PMID- 10948520
TI  - Ectopic expression in Drosophila.

PMID- 10948521
TI  - Clonal analysis in the examination of gene function in Drosophila.

PMID- 10948522
TI  - Application of antisense oligodeoxynucleotides in developing chick embryos.

PMID- 10948523
TI  - Application of functional blocking antibodies. N-cadherin and chick embryonic
      limb development.

PMID- 10948524
TI  - Gene expression analyzed by ribonuclease protection assay.

PMID- 10948525
TI  - Relative reverse transcription-polymerase chain reaction.

PMID- 10948526
TI  - Gene expression analysis using quantitative reverse transcription-polymerase
      chain reaction and a multispecific internal control.

PMID- 10948528
TI  - Gene expression analysis by in situ hybridization. Radioactive probes.

PMID- 10948527
TI  - In situ PCR detection of HIV expression in the human placenta.

PMID- 10948529
TI  - Radio-isotopic in situ hybridization on tissue sections. Practical aspects and
      quantification.

PMID- 10948530
TI  - mRNA and protein co-localization on tissue sections by sequential, colorimetric
      in situ hybridization and immunohistochemistry.

PMID- 10948531
TI  - Whole mount in situ hybridization to study gene expression during mouse
      development.

PMID- 10948532
TI  - Multicolor whole-mount in situ hybridization.

PMID- 10948533
TI  - Methods for double detection of gene expression. Combined in situ hybridization
      and immunocytochemistry of histochemistry.

PMID- 10948534
TI  - Visualization of the expression of green fluorescent protein (GFP)-linked
      proteins.

PMID- 10948535
TI  - Monoclonal antibodies in the analysis of embryonic development.

PMID- 10948536
TI  - Mesoderm induction in Xenopus. Oocyte expression system and animal cap assay.

PMID- 10948537
TI  - Amphibian organizer activity.

PMID- 10948538
TI  - Improved techniques for avian embryo culture, somite cell culture, and
      microsurgery.

PMID- 10948539
TI  - Neural crest cell outgrowth cultures and the analysis of cell migration.

PMID- 10948540
TI  - The chimeric human/mouse model of angiogenesis.

PMID- 10948541
TI  - Analysis of embryonic vascular morphogenesis.

PMID- 10948542
TI  - Epithelial-mesenchymal interactions.

PMID- 10948543
TI  - Methods for manipulating the chick limb bud to study gene expression, tissue
      interactions, and patterning.

PMID- 10948544
TI  - Palate development. In vitro procedures.

PMID- 10948545
TI  - In vitro fertilization.

PMID- 10948546
TI  - Trophoblast differentiation. An in vitro model for trophoblast giant cell
      development.

PMID- 10948547
TI  - Bone marrow-derived mesenchymal progenitor cells.

PMID- 10948548
TI  - Identification, characterization, and differentiation of human prostate cells.

PMID- 10948549
TI  - Preparation of chick striated muscle cultures.

PMID- 10948550
TI  - Study of skeletal myogenesis in cultures of unsegmented paraxial mesoderm.

PMID- 10948551
TI  - Embryonic limb mesenchyme micromass culture as an in vitro model for
      chondrogenesis and cartilage maturation.

PMID- 10948552
TI  - Electroporation-mediated DNA transfection of embryonic chick limb mesenchymal
      cells.

PMID- 10948553
TI  - Murine C3H10T1/2 multipotential cells as an in vitro model of mesenchymal
      chondrogenesis.

PMID- 10948554
TI  - Skeletogenesis. In vitro analysis of bone cell differentiation.

PMID- 10948555
TI  - Studying early hematopoiesis using avian blastoderm cultures.

PMID- 10948556
TI  - Isolation and culture of mouse germ cells.

PMID- 10948557
TI  - Cadherin-mediated cell-cell interactions.

PMID- 10948558
TI  - Analysis of hyaluronan using biotinylated hyaluronan-binding proteins.

PMID- 10948559
TI  - Microinjection of fluorescently labeled alpha-actinin into living cells.

PMID- 10948560
TI  - Pax3 and vertebrate development.

PMID- 10948561
TI  - Genetic-engineered models of skeletal diseases. I. Collagen type X.

PMID- 10948562
TI  - Genetic-engineered models of skeletal diseases. II. Targeting mutations into
      transgenic mice chondrocytes.

PMID- 10948563
TI  - Transgenic mouse models of craniofacial disorders.

PMID- 10948564
TI  - [Pharmacological profiles of the potent carbonic anhydrase inhibitor dorzolamide
      hydrochloride, a topical antiglaucoma agent].
AB  - Carbonic anhydrase (CA) plays an important role in the secretion of aqueous
      humor. The orally administered CA inhibitor acetazolamide lowers the intraocular
      pressure (IOP) of patients with glaucoma. However, approximately 50% of patients
      stop treatment with acetazolamide as a consequence of intolerable side effects
      due to the extraocular inhibition of the enzyme. This prompted attempts to
      develop a topically active CA inhibitor. Merck Research Laboratories focused on
      developing a water- and solvent-soluble compound to penetrate the cornea.
      Dorzolamide hydrochloride is a potent inhibitor of human CA isoenzyme II, with an
      IC50 value of 0.18 nM in vitro. In contrast, its inhibitory activity against
      human CA isozyme I is much weaker (IC50 value of 600 nM). Topically administered
      dorzolamide penetrated the ciliary body, inhibited its CA activity and had a
      hypotensive effect in rabbits; in contrast, topical administration of
      acetazolamide or methazolamide did not decrease IOP. In clinical trials,
      dorzolamide administered 3 times daily was effective in lowering IOP in patients
      with open-angle glaucoma or ocular hypertension. The hypotensive effect of
      dorzolamide 0.5% was similar to that of oral CA inhibitors or timolol (0.25%)
      twice daily. Dorzolamide did not induce the severe systemic adverse events
      associated with oral CA inhibitors. Dorzolamide was as effective as pilocarpine
      or dipivefrine as an adjunctive therapy in patients receiving beta-adrenergic
      antagonists. Dorzolamide also reduced IOP and accelerated retinal arteriovenous
      passage time in addition to improving visual function in patients with normal
      tension glaucoma.

PMID- 10948565
TI  - [Regulation of insulin release: analysis of the insulin secretory cascade and
      possible contribution to novel anti-diabetic drug development].
AB  - Insulin is the only 'hypoglycemic' hormone synthesized in and secreted from the
      pancreatic beta cell. Type 2 diabetes results from both secretory failure in the
      beta cell and insulin resistance in the target tissues for insulin. Attempts to
      develop anti-diabetic drugs that induce insulin secretion from residual beta
      cells in type 2 diabetic patients originate from the serendipitous discovery of
      sulphonylureas as hypoglycemic agents 60 years ago. Generally, secretion is
      carried out by sequential processes such as granule formation, intracellular
      traffic, granule docking/priming and the final step, exocytosis (secretory
      cascade). In the beta cell, recent progress in cell biology enables us to analyze
      each step in the secretory cascade and to reveal controlling mechanisms. This
      review describes regulatory mechanisms of insulin release by distinct nutrients,
      hormones and neurotransmitters, and roles of second messengers and protein
      phosphorylation in the insulin secretory cascade. Possible development of
      insulinotropic drugs for the treatment of type 2 diabetes has been also
      discussed.

PMID- 10948566
TI  - [Differentiation of cardiomyocyte].
AB  - In the recent decade, remarkable progress has been made in the field of cardiac
      development through the use of molecular, biological and genetic techniques.
      Several genes that regulate this process have been cloned, and their functions
      have been analyzed in vivo and in vitro. Cardiac-specific transcription factors,
      including Csx/Nkx-2.5, GATA4, MEF2 and dHAND/eHAND, play central roles in cardiac
      development. Loss-of-function of gain-of-function studies have revealed that
      these factors regulate heart morphogenesis and cardiac-specific gene expressions.
      Cardiac-specific genes, including MLC2v, cardiac alpha-actin and ANP, have
      specific binding sequences for transcription factors in their promoter regions
      and expressions of these genes are regulated by binding of transcription factors.
      In addition to the transcription factors, growth factors secreted from ectoderm
      and endoderm play important roles in induction of cardiomyocytes. Decapentaplegic
      and bone morphogenetic proteins, members of the transforming growth factor-beta
      superfamily, induce the expression of cardiac-specific transcription factors in
      the precardiac mesodrem and are indispensable to cardiomyocyte differentiation.
      We think that understanding the genetic cascade of cardiomyocyte differentiation
      will open the gate for cardiomyogenesis from non-cardiac cells.

PMID- 10948567
TI  - [Analgesic test using neonatal rat: quantification of algesic substance-induced
      body movement].
AB  - A novel analgesic test using neonatal rats was developed. In neonatal rats, body
      movement was induced by bolus, subcutaneous (s.c.) injection of algesic
      substances. The body movement was quantified by using a device composed of an
      audio speaker as a detector. Capsaicin, injected s.c., induced the body movement
      including scratching and struggling responses. The response peaked at 0-1 min and
      then decayed during the next 1-3 min. Furthermore, this method also detected that
      the magnitude of the response increased dose-dependently up to the maximum dose
      of 3000 ng. Endogenous algesic substances such as bradykinin, serotonin and
      histamine induced responses similar to those induced by capsaicin. Exogenous
      algesic substances such as formalin and acetic acid evoked more prolonged
      responses than those induced by capsaicin and endogenous substances. The effects
      of drugs on the capsaicin-induced response were examined in the following
      experiments. Opioid analgesics, morphine, buprenorphine and pentazocine,
      inhibited the response. Non-steroidal anti-inflammatory drugs, indomethacin,
      ibuprofen and acetaminophen, did not exert any effect on the response. Non
      steroidal anti-inflammatory drugs, indomethacin, ibuprofen and acetaminophen, did
      not exert any effect on the response. Neither the sedative diazepam nor the
      sedative chlorpromazine inhibited the response. It is concluded that this method
      is useful to quantify the body movement induced by noxious stimulation and is
      suitable for screening centrally acting analgesics with mu-opioid receptor
      agonist activity.

PMID- 10948568
TI  - [Effect of mexiletine on spontaneous sensory afferent activity in spontaneous
      diabetic rats (WBN/Kob rats)].
AB  - In this study, we investigated the hypothesis that mexiletine has an inhibitory
      action on spontaneous sensory afferent activity caused by small fiber neuropathy
      in diabetic rats (WBN/Kob rats). Gastric administrations of mexiletine (10 mg in
      0.3 ml saline) and the local anesthetic agent lidocaine (10 mg in 0.3 ml saline)
      were made in urethane-anesthetized rats. In 6 of 7 WBN/Kob rats (57-62 weeks of
      age), spontaneous afferent activity was observed and was significantly inhibited
      after administration of mexiletine, whereas it was not seen in either WBN/Kob
      rats (54 weeks of age) or Wistar SLC rats (31 and 35 weeks of age). This
      inhibitory action of mexiletine was sustained for more than 2 h after the
      administration. In contrast, lidocaine administration also inhibited the
      spontaneous nerve activity, but the magnitude of the inhibitory action was less
      than that of mexiletine. In another experiment, the afferent conductance velocity
      of the sural nerve was not affected after mexiletine was administrated in the
      WBN/Kob rats (62 weeks of age). The results suggest that pain mitigation of a
      diabetic prescribed with mexiletine may depend on the inhibitory effect of
      mexiletine on the generation of the spontaneous afferent action potentials by
      mexiletine in aged WBN/Kob rats, whereas mexiletine has no effect on the
      autonomic function of the afferent nerve.

PMID- 10948569
TI  - [Usefulness of the analytic method of intracellular calcium and the problems-
      aequorin and indo-1 signal].

PMID- 10948570
TI  - [Drug and pharmacology].

PMID- 10948571
TI  - [Drugs and pharmacology].

PMID- 10948572
TI  - [Drugs and pharmacology].

PMID- 10948573
TI  - [Cerebrovascular disease and gait disorders: qualitative and quantitative
      analysis].
AB  - INTRODUCTION AND OBJECTIVE: Pyramidal gait impairment (GI) is a classical trait
      of cerebrovascular disease (CVD). To developed a method to quantify prospectively
      and transversely GI and disequilibrium, to be applied in the screening of
      pyramidal and non-pyramidal syndromes associated to different ethiological
      subtypes of CVD; using an Index of Gait and Equilibrium (IGE). PATIENTS AND
      METHODS: In constructing IGE, we used 14 equally weighted semiological variables:
      6 measure balance, 6 gait, 1 sensitive abnormalities and 1 falls. Two
      neurologists separately examined each subject in the same day and repeating the
      evaluation after a week. Data analyses included Kruskal Wallis, chi 2, Spearman
      correlations and Principal Components. RESULTS: IGE was used in 90 subjects, 43
      males, with a mean age of 70.6 years. 3 groups of people were formed: 1. CVD (A,
      21 with silent vascular lesions diagnosed by imaging; B, 17 with vascular
      dementia; C, 21 with stroke); 2. 13 subjects with cautious gait, not associated
      to any disease; and 3. 18 normal control subjects (age 60-80 years). GI in the
      non-pyramidal syndrome were significantly related with small vessels disease (chi
      2 = 16.37, dof = 1, p < 0.001). CONCLUSIONS: GI in CVD, pyramidal and non
      pyramidal syndromes were equally frequent. Increased values of IGE caused by
      cautious gait in youngest non-stroke patients suggested high probability of
      silent CVD and significant association with small vessels disease. This
      preliminary assessment of IGE showed a reproducible and reliable tool for
      objectification and quantification of gait disorders.

PMID- 10948574
TI  - [Hyperuricemia as a risk factor for cerebrovascular accident: a case-control
      study].
AB  - INTRODUCTION: Although several collateral studies have been made of the
      relationship between hyperuricemia and cerebral vascular accidents (CVA), no
      definite conclusion has been reached. OBJECTIVE: To analyze the possible
      relationship between hyperuricemia and CVA. PATIENTS AND METHODS: We studied the
      cases and controls paired for age, sex and hospital. They included patients with
      CVA (125) and controls (250 ophthalmological patients). Both groups contained
      50.4% men and 49.6% women with an average age of 70 +/- 11 years. Data regarding
      vascular risk factors, a known personal history of hyperuricemia were recorded
      and serum uric acid levels determined in both groups. The relative risks were
      calculated using the Odds Ratio (OR) with a confidence interval of 95% (CI 95)
      and a conditional logistic regression study made. RESULTS: A statistically
      significant relationship was found between CVA and: arterial hypertension (OR:
      6.32; CI 95: 3.43, 11.65); smoking (OR: 3.79; CI 95: 1.36, 10.58); alcoholism
      (OR: 2.54; CI 95: 1.11, 5.41); ischemic cardiopathy (OR: 2.37; CI 95: 1.2, 4.70)
      and previous CVA (OR: 5.93; CI 95: 3.17, 11.09). No relation was found with: a
      history of hyperuricemia (OR: 1.53; CI 95: 0.63, 3.73), serum uric acid levels
      (OR: 0.86, CI 95: 0.36, 2.00 when the uricemia was between 5 and 5.99 mg/dl and
      OR: 0.46, CI 95: 0.21, 1.02, when the uricemia was over 6 mg/dl). CONCLUSION: Our
      results suggest that hyperuricemia is not an independent risk factor for CVA.

PMID- 10948576
TI  - [Effects of monaural and binaural stimulation on middle latency auditory evoked
      responses].
AB  - INTRODUCTION: Middle latency evoked potentials include a series of evoked
      responses which encompass/include myogenic potentials (which translate the
      existence of sonomotor reflexes), and others which are clearly of neurogenic
      origin. The latter are the most useful from the clinical point of view.
      OBJECTIVE: To evaluate the effects of monoaural (MA) and binaural (BA)
      stimulation on middle latency auditory evoked potentials. PATIENTS AND METHODS:
      We studied 15 healthy people, aged between 18 and 52 years, in whom Cz recording
      electrodes had been fitted to both short-circuited external ears with Fpz as
      earth. The stimuli used were alternate clicks of condensation and rarefication of
      90 dBHL, first BA and them MA. The auditory evoked response from the brain stem
      was also recorded. RESULTS: We found more stability of most of the components
      evaluated during biauricular stimulation. All subjects had Pa waves and 93% had
      Pb waves. Statistically significant differences were only found for the amplitude
      of Po and Pa (BA against RE) (Wilcoxon test, p < 0.05). CONCLUSION: The use of BA
      stimulation to obtain middle latency evoked potentials is more useful for study
      of the more rostral parts of the auditory path, since its components are more
      stable.

PMID- 10948575
TI  - [Diabetes mellitus and stroke].
AB  - INTRODUCTION: Diabetes mellitus (DM) is an important risk factor in cerebral
      vascular disease since it causes endothelial proliferation and thickening of the
      plasmatic membrane in the small blood vessels. The pathogenic mechanism is thus
      different from that of athero-thrombosis or emboli. Our objective was to
      determine whether there are differences between strokes in diabetic patients and
      strokes secondary to other diseases. PATIENTS AND METHODS: We made a prospective
      study of 415 stroke patients admitted to hospital consecutively over one year.
      Transient ischaemia and subarachnoid hemorrhage were excluded. We analysed age,
      sex, risk factors, severity (Canadian scale), mortality and functional prognosis
      one week later. RESULTS: Of the 415 patients, 354 were diagnosed as having
      cerebral infarcts and 61 parenchymatous hemorrhage. The average age was 72.2
      years. The commonest risk factor was arterial hypertension (n = 241). There were
      95 patients with DM. Bivariate and multivariate analysis showed independent
      variables associated with DM to be the onset of cerebrovascular pathology at a
      younger age (p = 0.009), association with arterial hypertension (p = 0.002) and
      poor previous quality of life (p = 0.003). We did not find a higher incidence of
      lacunar infarcts amongst the diabetic patients. CONCLUSIONS: The diabetic patient
      is younger and often also has arterial hypertension. There was no difference in
      mortality or type of stroke (ischemic compared with hemorrhagic). No significant
      relationship was found with lacunar infarcts.

PMID- 10948577
TI  - [The use of lamotrigine in the psychosocial readaptation of patients with
      epilepsy].
AB  - INTRODUCTION AND OBJECTIVES: Epilepsy is a chronic illness which causes
      psychosocial problems in the patients affected. These disorders may be
      investigated by using the Washington Psychosocial Inventory (WPSI). We wish to
      show the variables which affect the WPSI most and also the changes seen in the
      results of this test and the control of seizures after treatment with lamotrigine
      for a year. PATIENTS AND METHODS: Using the WPSI, we studied 70 patients in the
      epilepsy outpatient clinic of the Psychiatric Hospital in La Habana during the
      period February-March 1998. The results of the WPSI were analysed according to
      the following variables: cerebral lesion, age of onset of epilepsy, frequency of
      seizures, more than one seizure per patient, and the antiepileptic drug used. The
      patients were followed-up during one year of treatment with lamotrigine, and the
      WPSI was repeated after one year (in March 1999). The following statistical tests
      were used to find the level of significance: variance analysis, standard
      deviation, chi deviation and difference between means. RESULTS: The WPSI showed
      initially, at almost all levels, poor scoring; 48.86% had generally poor
      psychosocial function (FPG). Only the greater frequency of seizures significantly
      altered the WPSI. After treatment with lamotrigine for one year there was better
      seizure control, a better WPSI result and only 11.43% had poor FPG. CONCLUSIONS:
      We consider that the high frequency of seizures is the variable which most
      affects the WPSI and that lamotrigine is useful both for control of epileptic
      seizures and to obtain psychosocial rehabilitation.

PMID- 10948578
TI  - [Epidermal growth factor-responsive precursors with similar properties isolated
      from embryonic rat septum and striatum].
AB  - INTRODUCTION: The potential correspondence of precursor cells isolated from
      different brain regions is partially unknown. Since models and culture conditions
      used in several studies vary, comparison of precursor characteristics has been
      limited. OBJECTIVE: In this paper epidermal growth factor (EGF)-responsive
      precursors from the striatum and septum were isolated and their growth pattern in
      vitro were determined. We also evaluated the influence of fibroblast growth
      factor (FGF) and nerve growth factor (NGF) on the proliferation of these cells.
      MATERIAL AND METHODS: Dissociated cells from rat septum and striatum were
      cultivated in suspension with 20 ng/ml of EGF. Total cells quantification,
      immunocytochemical staining and neuron counts were used to evaluate cell
      proliferation and cellular phenotypes produced by EGF-generated cells. RESULTS:
      Considering both culture evolution and cellular growth we demonstrated a similar
      growth pattern of septal and striatal EGF-responsive precursors. Furthermore, the
      proliferation of both cells populations was supported by FGF. On the contrary,
      NGF neither had a proliferative effect nor affected cell survival. Upon
      differentiation, a small proportion of precursor cells differentiated into
      neuronal phenotype.

PMID- 10948580
TI  - [Carlevoix-Saguenay type recessive spastic ataxia. A report of a Spanish case].
AB  - OBJECTIVE: To present the first Spanish case, perhaps the first non-Canadian,
      with ataxia type Charlevoix-Saguenay. CLINICAL CASE: A patient with important
      psychomotor delay and non-progressive ataxia has been studied in our Service
      during the first years of life and his follow-up has been carried out until 30
      years of age. He has been studied from the clinical, ophthalmological and
      neuroradiological with magnetic resonance point of views. RESULTS: Ataxia and
      psychomotor delay showed a non-progressive evolution. The patient showed
      myelinated retinal fibers and atrophy of the superior half of the cerebellum.
      CONCLUSION: Neurological, ophthalmological and magnetic resonance images showing
      atrophy of the superior part of the cerebellum are the three main signs of the
      ataxia type Charlevoix-Saguenay. This patient could be the first case reported
      out Canada.

PMID- 10948579
TI  - [Potentially treatable subacute forms of infection due to the HTLV-1].
AB  - INTRODUCTION: Tropical spastic paraparesis due to HTLV-I virus is diagnosed at
      very advanced stages, when there is spinal atrophy present and so only
      symptomatic treatment can be given. Early diagnosis of HTLV-I infection in
      unusual syndromes and the use of corticosteroids may help to slow the development
      of the disease. CLINICAL CASES: We describe two Brazilian patients who developed
      symptoms due to HTLV-I present for less than one year: subacute myelopathy with a
      sensory level and an ataxic pyramidal syndrome associated with axonal neuropathy,
      which partly improved after treatment with corticosteroids. RESULTS: A 50 year
      old woman presented with progressive paraparesis following pain, cramps, feeling
      that her legs had 'gone to sleep' and sphincter dysfunction over the previous
      eleven months. Spinal MR showed a diffuse spinal hypersignal at D2. The 60 year
      old man had developed an ataxic syndrome and axonal polyneuropathy over the
      previous ten months. In both patients the anti-HTLV antibodies in blood and CSF
      were positive on ELISA as later confirmed by Western-blot. Thorough biochemical
      study ruled out other infectious etiologies. Both patients were treated with
      corticosteroids (i.v. methylprednisolone and oral prednisone respectively) and
      their symptoms improved, particularly the joint pains, ataxia and the 'gone to
      sleep' sensation of the legs. CONCLUSIONS: The ataxic syndrome and myelopathy due
      to HTLV-I, when these have been diagnosed early, may benefit from corticosteroid
      treatment and progression of the disorder be prevented. The myelitic phase of
      HTLV-I infection is associated with diffuse myelopathy, which was unusually seen
      in our first patient on spinal MR.

PMID- 10948581
TI  - [Hereditary neuropathy with liability to pressure palsies in childhood].
AB  - INTRODUCTION: The diagnosis of hereditary neuropathy with liability to pressure
      palsies during childhood is uncommon, since the disorder is still asymptomatic
      and the clinical features are nonspecific. CLINICAL CASE: We present a case of
      hereditary neuropathy with liability to pressure palsies in a seven and a half
      year old girl with deteriorating clinical findings of 'pies cavos', scoliosis,
      difficulty in walking and torticollis, but without episodes of paralysis. On the
      electroneurographic (ENG) study numerous anomalies of sensory and motor nerve
      conduction were seen, especially at sites of nerve trapping, both in the patient
      and in her mother; genetic study showed deletions of chromosome 17p11.2 in both.
      CONCLUSIONS: Hereditary neuropathy with liability to pressure palsiesin childhood
      may follow a course which does not show typical pressure palsies. Therefore the
      ENG study is very important for detection of the disorder. Torticollis, as well
      as pies cavos and scoliosis, is frequently seen in neuropaediatric clinics, so
      the possibility, as in the case reported, that this is part of the clinical
      spectrum of hereditary neuropathy with liability to pressure palsies should be
      considered. With diagnostic confirmation on genetic studies, nerve biopsy is not
      necessary.

PMID- 10948582
TI  - [Disseminated acute encephalomyelitis with fatal evolution: clinicopathological
      study].
AB  - INTRODUCTION: Disseminated acute encephalomyelitis is a monophasic demyelinating
      disease which progresses rapidly and is often fatal. It is an autoimmune
      condition, mediated by T lymphocytes, in which the immune response is directed
      against the myelin antigens. CLINICAL CASE: We describe the clinical,
      radiological and neuropathological findings in the case of a 31 year old woman
      who, ten days after complaining of a clinical condition of upper respiratory
      tract inflammation, presented with unilateral focal neurological signs,
      subsequent rapid deterioration of consciousness and death. On autopsy the
      neuropathological characteristics of disseminated acute encephalomyelitis were
      seen. CONCLUSIONS: The relative rarity of this condition at the present time
      makes clinical diagnosis difficult. The differential diagnosis with other
      conditions may be difficult also. Thus, this disease often leads to a
      neuropathological diagnosis.

PMID- 10948583
TI  - [Pseudotumor cerebri associated with maxillary sinusitis: clinico-pathological
      study].
AB  - INTRODUCTION: The pseudotumor cerebri is characterized by increased intracranial
      pressure in the absence of a space occupying lesions or obstruction to the
      circulation of cerebrospinal fluid (CSF). Increased pressure but normal
      composition of the CSF is the diagnostic criterion. Ear infections and other
      infections such as sinusitis have been cited as possible, but rare, causes.
      CLINICAL CASE: A 12 year old girl presented with diplopia 10 days after starting
      treatment for sinusitis. On examination there was paresia of the VI cranial nerve
      to the left eye and marked bilateral papilledema. She had normal visual acuity
      with visual field measurements showing increased blind spot field in both eyes.
      Resonance studies only showed maxillary sinusitis. CSF pressure was 35 cm H2O,
      with 40 lymphomonocytes and normal biochemical findings. After 15 cm of CSF had
      been removed treatment was started with acetazolamide, dexamethasone and
      cefotaxime. A week later the diplopia had disappeared and the CSF pressure was
      25, with no cells present. Two months later the visual fields and fundus oculi
      were normal. After follow-up for one year there was no recurrence. CONCLUSIONS:
      We describe a case of pseudotumor cerebri associated with maxillary sinusitis. We
      do not know whether this is a chance association or whether there was a
      pathophysiological basis. The possibility should be considered so as to treat the
      cause or predisposing factor. The initial CSF pleocytosis would support the
      possibility of a relationship of the pseudotumor with an infectious condition
      (meningeal irritation or para-infectious pleocytosis meningeal irritation or para
      infections pleocytosis in the context of an ENT infection), which might have
      precipitated the problem by interfering with the reabsorption of CSF.

PMID- 10948585
TI  - [Binswanger disease: a common type of vascular dementia].
AB  - OBJECTIVE: This document intends to review the main features of Binswanger's
      disease and its differential diagnosis with other vascular pathologies of the
      white matter. DEVELOPMENT: Nowadays, the raise of the elderly group of population
      has led to a remarkable increase in dementia's prevalence, therefore it becomes
      necessary to study deeply vascular dementias, the second most common kind of
      dementia behind Alzheimer's disease. The detection of Binswanger's disease has
      increased due to the progress of neuroimaging techniques, that allow to identify
      ischemic lesions situated in the cerebral white matter and the existence of
      multiple lacunar infarcts. This clinical entity represents the most frequent type
      of subcortical dementia, although controversy still remains about its pathogeny,
      ethiology, and nosologic limits. CONCLUSIONS: The search for unified criteria is
      the first step in the microangiopathic subcortical dementia's field to achieve
      valuable treatment strategies.

PMID- 10948584
TI  - [Malignant gliomas. Oncogenic considerations].
AB  - INTRODUCTION: There is evidence that cancer is the result of an accumulation of
      genetic alterations which lead to uncontrolled cell proliferation with loss of
      the processes of cell differentiation. DEVELOPMENT: In this review we try to
      explain the molecular alterations which occur in the anaplastic degeneration of
      astrocyte gliomas, conditioned by loss of genetic material on chromosomes 10 and
      17, mutation of gene p53, amplification of the receptor of the epidermic growth
      factor, translocations of chromosomes 9p, 13q, 19q and 22q amongst others. On
      clinical and molecular studies two basic genetic pathways in the development of
      glioblastoma multiform have been identified. One of progressive degeneration of
      an astrocytoma of low-grade malignancy and the other from normal neuroglial cells
      such as a glioblastoma multiform de novo. CONCLUSIONS: The oncogens and tumor
      suppressive genes are the basis of the lack of control and abnormal cellular
      proliferation. An understanding of the changes which they cause will in future
      permit the application of new therapeutic options in patients with malignant
      astroglial neoplasias.

PMID- 10948586
TI  - [Abnormal movements. Historical notes].
AB  - Most of the knowledge about movement disorders comes from the last fifty years.
      However, the ancients made some remarkable neurological depictions. We still can
      find some neurological descriptions including Parkinson's disease in the Bible,
      and the ancient writings of Atreya and Susruta. In addition, classic tests
      provide us of valuable information on historical personages, including the
      dystonia of Alexander the Great.

PMID- 10948587
TI  - [Experimental models, of Parkinson disease].
AB  - This article reviews the most useful animal models of Parkinson's disease
      available. Basically they include the model of unilateral nigrostriatal lesion
      induced by 6-hydroxydopamine (6-OHDA) in rodents and the 1-methy-4-phenyl
      1,2,3,6, tetrahydropyridine (MPTP) model of parkinsonism in non-human primates.
      The major neurochemical and histological alterations found in these two models
      are also analyzed. Finally, possible applications of these models of parkinsonism
      are also discussed.

PMID- 10948588
TI  - [Neuronal activity in the subthalamic nucleus in Parkinson disease].
AB  - INTRODUCTION: The subthalamic nucleus has been demonstrated to be involved in
      Parkinson's disease. Electrical stimulation of this nucleus at high frequency was
      proved to revert most symptoms and is used as the most advanced alternative
      therapy. The technique requires the recording of single cell activity as an
      important step in locating spatially the limits of the nucleus together with
      magnetic resonance imaging and ventriculography. OBJECTIVES: To study the
      electrophysiological properties of single cells in the subthalamus. This
      information is important to recognize the nucleus in the operating room so as to
      implant the definitive stimulating electrode. PATIENTS AND METHODS: Twelve
      patients with Parkinson's disease were implanted with bilateral electrodes in the
      subthalamic nucleus. Several neurological tests were applied during one year to
      study the clinical results. RESULTS: Single cell activity was recorded in both
      hemispheres. Three types of cells were recognized based on the mode of discharge:
      tonic, phasic and rhythmic. The track chosen to implant the definitive electrode
      was based on the higher number of cells recorded and on the response to tremor
      and passive or voluntary movements. The neurological tests applied demonstrated a
      diminution of the symptoms. CONCLUSION: The subthalamic nucleus plays an
      important role in handling motor and sensory information. Stimulation of the
      nucleus at high frequency reveals an amelioration of Parkinson's symptoms during
      the one year period of study.

PMID- 10948589
TI  - [Paroxysmal movement disorders].
AB  - INTRODUCTION: Paroxysmal movement disorders are of sudden onset, paroxystic or
      intermittent, with normality or at least absence of abnormal movements between
      episodes. They are uncommon conditions with high familial incidence. The
      commonest form is paroxystic dystony. Paroxystic ataxia and paroxystic tremor are
      much rarer. DEVELOPMENT: Paroxystic dystony is seen clinically as paroxystic
      episodes of variable duration, consisting of dystonic movements and postures
      which present spontaneously or are triggered by certain stimuli or situations.
      There are different types: kinesgenic paroxystic choreoathetosis, dystonic
      paroxystic choreoathetosis, intermediate paroxystic choreoathetosis and nocturnal
      paroxystic choreoathetosis. The paroxystic ataxias are characterized by recurrent
      episodes of ataxia in the absence of any known metabolic defect. In type 1
      episodic ataxia there are also episodes of ataxia and myochemical changes. The
      gene responsible for this condition has been found on the short arm of chromosome
      12. Type 2 episodic ataxia is characterized by its excellent response to
      acetazolamide. The gene responsible is found on the short arm of chromosome 19.
      CONCLUSION: Very few cases of paroxystic tremor have been described.

PMID- 10948590
TI  - [Changes in gait in the elderly].
AB  - Disorders of gait are a common problem in elderly people. It is estimated that
      over 15% of people aged over 65 years have disorders of gait. Disorders of
      balance are also common in old age, with increased risk of falling and lesions
      due to falls. Every year 20-30% of the elderly people living alone have falls.
      The causes of poorer control of balance in old age are not clear. Usually
      instability is multifactorial.

PMID- 10948591
TI  - [A 45-year-old patient with loss of consciousness].

PMID- 10948592
TI  - [Spanish national neurology (psychiatry). The work of Vallejo Najera and Lopez
      Ibor].
AB  - After the Civil War, Spanish science underwent a profound crisis. The promising
      neurology of Madrid, which went hand in hand with psychiatry, collapsed since its
      leading figures were on the Republican side. The new leaders, Vallejo Najera and
      Lopez Ibor, gradually abandoned the neurological aspect so that this disappeared,
      and from a psychiatric point of view tried to support the new dominating ideas
      based on German national-socialism (German national psychiatry). Their 'pure'
      neurological work is limited, although of interest, since it represents the scant
      output of our specialty during those years.

PMID- 10948593
TI  - [Intracranial tuberculomas in an immunocompetent patient].

PMID- 10948594
TI  - [Intradural retroclival epidermoid cyst. A case report].

PMID- 10948595
TI  - [The evaluation of oxidative stress in a patient with transient cerebral
      ischemia].

PMID- 10948596
TI  - [A genetic study of 64 patients clinically suspected of having Angelman's
      syndrome].

PMID- 10948597
TI  - [Effect of the Stellamune Mycoplasma vaccine on growth, energy conversion, death,
      and medication use in fattening pigs on a pig farm chronically infected with
      Mycoplasma hyopneumoniae].
AB  - The effect of Stellamune Mycoplasma vaccine, administered to piglets aged 2-15
      days and then 13-15 days later, on daily weight gain, energy conversion, and use
      of medication was examined in fattening pigs on a chronically Mycoplasma
      hyopneumoniae infected pig farm. Half of the piglets were vaccinated and the
      other half acted as controls. In the study design, half of the pens in the
      fattening unit were allocated to vaccinated pigs; the other half to non
      vaccinated pigs, pen was the experimental unit. In the fattening pens sows and
      castrated boars were separated. The study consisted of a total of 37 pens with
      vaccinated, and 37 pens with non-vaccinated pigs in 12 different compartments
      within the pig herd. In the finishing period, mean growth performance and mean
      energy conversion (EV/kg) of vaccinated animals was 65 grams/day higher and 0.07
      EV/kg lower than in control pigs. Furthermore, the incidence of individual
      curative medication against respiratory problems was more than 4 times higher in
      control pigs than in vaccinated pigs. There was a tendency for a higher number of
      group medications against respiratory problems in control pigs than in vaccinated
      pigs. It is concluded that, in this herd, vaccination against M. hyopneumoniae
      was successful from an economic point of view.

PMID- 10948598
TI  - [Regulation of atrial fibrillation in horses with oral quinidine sulfate.
      Discussion of the disease picture in a typical case].
AB  - Atrial fibrillation is a disorder of cardiac rhythmicity, and its importance in
      the horse depends on the underlying cause and the function of the horse. Before
      the decision is taken to start treatment, it has first to be ascertained whether
      treatment is worthwhile and whether the horse is an appropriate candidate for
      treatment. This article gives a short overview of current opinion on the cause
      and treatment of atrial fibrillation in the horse. The most used treatment at the
      moment, oral chinidine sulphate, is discussed. The hemodynamic consequences of
      atrial fibrillation and the response of a patient to treatment with chinidine
      sulphate are also discussed.

PMID- 10948599
TI  - [Interview with professor of veterinary anesthesiology Ludo Hellebrekers: "I just
      feel responsible".(Interview by Sophie Deleu)].

PMID- 10948600
TI  - [Meeting concerning the veterinary medicine of the pig by Cehave-Landbouwbelang.
      Newest insights in nutrition and health].

PMID- 10948601
TI  - [Porcine reproductive and respiratory syndrome round table discussion].

PMID- 10948602
TI  - [The critical consumer, the influence of the consumer on the use of veterinary
      medicine].

PMID- 10948603
TI  - [Preliminary research on the occurrence of antibodies against influenza viruses
      in chicks in the Netherlands. Discussion about monitoring diseases at slaughter 
      ].

PMID- 10948604
TI  - [The veterinary disciplinary board. A disqualified horse approved after all].

PMID- 10948605
TI  - [A response to: Looking back at the beginning and end of the Dutch Association of
      Women Veterinarians].

PMID- 10948606
TI  - [A good group great idea: the veterinarian cooperative AUV].

PMID- 10948607
TI  - [Sellers of products derived from animals].

PMID- 10948608
TI  - [Transponder registration firms].

PMID- 10948609
TI  - [The basic problems and outlook for assisted reproductive technologies].
AB  - In this article the authors discuss some problems in ART:COH, stimulation
      protocols, culture media, transfer of embryos, luteal phase support, ethical,
      financial, religious and legal problems etc. Tha main complications are
      discussed, toosyndrom and pseudosyndrom of the empty follicle, OHSS, multiple
      pregnancy. In these cases the prophylactic and therapeutical measures are pointed
      out. Finally the main perspectives and developments of ART in the new millennium
      are outlined.

PMID- 10948610
TI  - [The use of prostaglandins in prolonged pregnancy and their effect on the newborn
      infant].
AB  - OBJECTIVE: The purpose of this study was to evaluate the neonatal outcome in
      newborns from mothers with post-term pregnancy and vaginal prostaglandin (Prostin
      E2) for cervical ripening and labor induction. STUDY DESIGN: This prospective
      study included 82 newborns, w.g. 41-42, divided into three groups according to
      the management of post-term pregnancy: group I--preinduction with Prostin E2
      before induction of labor with oxytocin; group II--induction with oxytocin only;
      group III--with expectant management. In each newborn group weight, size, head
      circumference, Apgar score and neonatal morbidity characteristics were noted.
      RESULTS: The cesarean delivery rate was 14.2% in group I, 12.9% in the group II
      and 3.3% in the III-d group. There were no significant differences between groups
      in the frequency of meconial amniotic fluid, neonatal meconium aspiration. The
      incidences of severe asphyxia, neonatal injury and pathologic neonatal icter were
      higher in the group I. CONCLUSIONS: Prostin E2, used for the cervical ripening
      and labor induction with oxytocin increased the rate of surgical interventions at
      delivery and neonatal morbidity.

PMID- 10948611
TI  - [The use of prostaglandins in atonic uterine hemorrhages following vaginal
      delivery].
AB  - The authors examine the results of usage of Prostin 15M (Upjohn) in series of 19
      women with hypotonic uterine bleeding after vaginal delivery. For the same period
      (1997) 1179 deliveries were performed in the Department of Obstetrics and
      Gynecology in HMS-Plovdiv. Positive effect was noted in 16 of the cases (84.22%).
      Unsatisfactory effect was marked in 3 of the cases--15.78%. Three of the women
      demonstrated adverse reactions after application of Prostin 15M.

PMID- 10948612
TI  - [The dynamics and structure of neonatal mortality in Bulgaria in the period of
      1989-1998].
AB  - AIM OF THE STUDY: To follow and analyse the state and the structure of neonatal
      mortality rate (NMR) in the last ten years in Bulgaria. MATERIAL AND METHODS: A
      retrospective study is fulfilled on the annual data of the National Health
      Statistic Institute concerning the NMR in a period of last ten years. Along to
      this the changes in the perinatal infant mortality rate (PIMR) including the
      stillbirth and the early NMR are studied. The results are analysed by a
      comparative method and presented graphically. RESULTS: The unfavorable trends in
      the social and economic development of Bulgaria in the last decade are associated
      with a constant increase of PIMR--from 10.8% in 1989 to 12.9% in 1998, and of its
      components respectively: the stillbirth--from 5.9% to 7.4% and of the early NMR-
      from 4.9% to 5.8%. The NMR has increased from 7.3% since 1989 to 8.3% in 1998,
      the highest level being in 1991--10.4%. Besides the level of prematurely has
      increased constantly for the recent ten years--from 6.5% to 9.6%. The leading
      causes of neonatal mortality in Bulgaria are: perinatal asphyxia, congenital
      malformations, neonatal respiratory distress syndrome (RDS) and perinatal
      infections. They have remained the same for the recent five years. From them only
      the mortality caused by perinatal asphyxia has decreased in 1998--to 41.3% in
      comparison with 1994--43.7% and by congenital malformations--from 29.4% to 23.4%
      in 1998, the highest reduction being of the malformations of the neural system (2
      folds) and of the gastrointestinal system (5 folds). The NMR of the low-birth
      weight infants (birth weight < 2500 g) has been 58.1% in 1997 and of the very low
      birth weight infants (< 1500 g)--276.3%. The NMR of both groups premature infants
      has decreased in 1998, respectively--to 47.6% and 191.4%. The NMR of the term
      born infants has been 13.2% in 1997 and 11.1% in 1998. CONCLUSIONS: The NMR in
      Bulgaria remains comparatively high, the larger part being on the account of the
      early NMR, and it has increased for the last ten years. The main causes of NMR
      have remained the same for the last five years in the leading place been the
      perinatal asphyxia, the congenital malformations and the neonatal RDS. There is a
      tendency to a decrease of the perinatal asphyxia and the congenital malformations
      as a course of NMR in the last five tears. The NMR of the premature infants has
      decreased in 1998 and is relatively low, but this may be due to the fact that a
      certain part of the deceased extremely low-birth weight infants (< 1000 g) has
      been still not registered.

PMID- 10948613
TI  - [A clinico-epidemiological study of neural tube defects in newborn infants].
AB  - This is a retrospective study on the rate of inborn defects of neural tube in
      University Hospital of Obstetrics and Gynaecology--Sofia for two 5-years-long
      periods of time: from 1986 to 1990 and from 1993 to 1997. The results show an
      increasing rate of inborn NTD during the second period of time which can be
      partly explained by the fact that the hospital is National Perinatal Centre where
      high risk pregnancies and deliveries are concentrated. Most disturbing is the
      fact that more than half of life-born and still-born infants with NTD are at an
      age of gestation higher than 34 g.w. This is a result of late perinatal diagnosis
      of these defects and brings up serious psychological, social and economical
      problems.

PMID- 10948614
TI  - [Congenital anomalies among live-birth infants and their place in the structure
      of neonatal mortality--the Higher Medical Institute, Pleven (1993-97)].
AB  - The aim of the study was to determine the frequency of the congenital anomalies
      (CA) among the live-born (LB), the structure of the neonatal mortality (NM) and
      the impact of congenital anomalies on it. Congenital anomalies were found in 171
      (2.71%) of 11,902 infants born and hospitalized at the Clinics of Neonatology-
      Pleven between 1993 and 1997. 171 (14.4% o) of all LB died in 28 day after
      delivery. Noninfectious lung pathology and CA were responsible for respectively
      28.7% and 27.5% of these deaths and were the main causes of NM. Multiple
      congenital anomalies and CA of cardio-vascular system were the most frequent CA
      that caused these deaths. The major part of the CA with genetic basis (64%)
      emphasizes the importance of the registration of CA and the genetic counselling
      for declining the NM rate.

PMID- 10948615
TI  - [Spontaneous abortions in Sneddon's syndrome].
AB  - Following the publications on the connection between Sneddon's syndrome and the
      antiphospholipid++ syndrome, the attention of researchers concentrated on the
      reproductive problems of women comprising the greater part of patients suffering
      from Sneddon's syndrome. One of the main indications of these almost coinciding
      syndromes are miscarriages for no obvious reason. It is supposed that the general
      mechanism is thrombosis. In a group of 38 patients with Sneddon's syndrome 32
      (84%) are women. Twenty-eight of them have altogether given bright 43 times.
      Seven of them have suffered miscarriages for no obvious reason and three have
      habitual miscarriages. Three women have sterility problems.

PMID- 10948616
TI  - [The correlation between intrauterine filling defects during
      hysterosalpingography and endometriosis at laparoscopy].
AB  - The association of intrauterine filling defects on hysterosalpingogram with
      endometriosis was evaluated. One hundred twenty patients were prospectively
      investigated with both methods, hysterosalpingography (HSG) and laparoscopy
      (LSC), for period of two years. HSG was performed on days 7-10 with water-soluble
      contrast medium. The presence of endometriosis was proved laparoscopically and
      scored according to the American Fertility Society classification. Forty-one
      women had endometriosis at LSC. In 25 of all 30 women with filling defects on
      hysterosalpingogram endometriosis was found. The presence of intrauterine filling
      defects on HSG is significantly associated with the presence of pelvic or
      peritoneal endometriosis.

PMID- 10948617
TI  - [The use of SIT and ELISA to detect serum sperm antibodies in infertile
      patients].
AB  - The existence of natural sperm antibodies in fertile subjects requires the
      application of additional methods in certain cases of significant, but near to
      the borderline agglutinating titers, in order to distinguish between pathological
      and natural sperm antibodies. We applied the sperm immobilization test (SIT) of
      Isojima and an enzyme-linked immunosorbent assay (ELISA) with sera from infertile
      patients (n = 66) that have been positive in at least one of the agglutination
      methods of Kibrick and Friberg. The data were compared with the results for a
      control group of blood donors (n = 50). It was demonstrated that the positive,
      but low-titer sera in the test of Friberg were often highly positive in ELISA,
      while the high-titer sera displayed lower OD values. No such correlation was
      established by SIT. Probably, it would be practical to use ELISA in cases, where
      no convincing laboratory data exists for immunity against spermatozoa--relevant,
      but low agglutinating titers, which can be found in fertile subjects. Besides,
      SIT and ELISA can recognize antigen-antibody systems different from those
      identified by the agglutinating tests.

PMID- 10948618
TI  - [The microbial findings in leukorrhea].
AB  - During two periods /1984/86 and 1998/01.00/ were studied microbial findings from
      vaginal specimens of women in reproductive age /16-48/. Candida spp. was isolated
      most frequently /17.3% to 21.5%/. BV was increased from 4.6% to 13.1%. T.
      vaginalis was decreased from 8.7% to 1.8%, probably as a consequence of
      metronidazole appliance.

PMID- 10948620
TI  - [The copper concentration in the blood serum of women with ovarian tumors (a
      preliminary report)].
AB  - The aim of the present study was to evaluate serum copper concentration changes
      in patients with benign cysts or carcinomas of ovary, and to compare these
      concentrations with the normal reference serum copper levels. Patients included
      in the study were as follows: benign ovarian cyst cases (n = 19), endometrial
      cyst cases (n = 5), ovarian carcinoma cases (n = 6), female patients with no
      ovarian disease (n = 161). Reference serum copper levels in apparently healthy
      subjects were 16.8 +/- 4.15 mumol/l (mean +/- SD). Serum copper concentration
      were significantly increased in ovarian carcinoma patients (22.98 +/- 3.90
      mumol/l) in comparison with benign cyst patients (18.40 +/- 4.61 mumol/l) (p <
      0.05), in with endometrial cyst patients (15.94 +/- 4.24 mumol/l) (p = 0.02), and
      in comparison with normal levels in controls (p < 0.001). Copper/zinc ratios were
      highest in ovarian carcinoma patients--1.68, intermediate in benign cyst patients
      -1.42, and lowest in endometrial cyst patients--1.08. The mechanisms underlying
      serum copper concentration variations in the different groups are briefly
      discussed with special emphasis on these in ovarian carcinoma patients.

PMID- 10948619
TI  - [The treatment of bacterial vaginosis with Dalacin V cream].
AB  - To asses the efficiency of the 2% clindamycin phosphate creme given in 3 and 7
      daily courses officially designer for the treatment of bacterial vaginosis (BV).
      METHODS: The study includes 65 patients who have microbiological data for BV 11
      of the women are pregnant (18.46%). The microbiological study includes there
      agent: Streptococcus agalactiae, E. colli, Gardnerella vaginalis,
      Peptostreptococcus species, Prevotella species, Mobiluncus species,
      Staphylococcus epidermidis et Enterococcus fecalis. The controls visit was
      assessed on the 7'] and 28'] day after the therapy. RESULTS: There were
      successful results on the 84.3% of the patients after 7 day course but in the 3
      day course the good results were showed in 73.91% of the women. After the 28"]
      day there were only few successful results 43%. CONCLUSIONS: The clindamycin
      phosphate is more preferable method for the treatment of BV.

PMID- 10948621
TI  - [IUGR--the current aspects].

PMID- 10948622
TI  - [Intracytoplasmic sperm injection (ICSI)--a current approach to treating
      sterility].

PMID- 10948623
TI  - [Polycystic ovaries--their ultrasonic diagnosis].
AB  - Polycystic ovaries are present like a two type: peripheral and cystic form. At
      the first cystic formations are disposed subcapsularis, at the second they are in
      the stromal zone. To have polycystic ovary syndrome the patient must have
      polycystic ovaries on (MI ultrasound and one or more of the following:
      oligo/amenorrhea, hirsutism/acne, raised LH:FSH ratio, higher of 2.5 or raised
      circulation androgens. The LH:FSH ration is higher in patient--with peripheral
      form. The basal morphological changes for estimation of the ovarian structure
      are: doubly ovarian volume, approximately in 50%, increased in number of atretic
      follicules, 30% increased the cortical stroma and five enlarging of the medullar
      stroma. Early Doppler studies have demonstrated increased stromal vascularity if
      correlated with raised LH/FSH ratio and raised androgens level. It was found
      increased impedance in uterine artery and decreased of PI (pulsatility index).
      There are difference between patient with peripheral and cystic form on Doppler
      examinations. In the first group have lower pulsatility index in the ovarian
      artery, higher stromal vascularity and LH/FSH ratio and increased score 2. All
      present results of investigations determine the criteria to present ovarian
      structure in context of PCOS as using conventional and Doppler ultrasonographic.

PMID- 10948624
TI  - [Fetal pulse oximetry: a clinical methodological study].
AB  - The aim of the study is to provide preliminary assessment of the possibilities of
      fetal pulse oximetry as a method for monitoring of fetal pulse rate and oxygen
      saturation during labour. The study includes 65 pregnant women during active
      labour at term--all with one fetus and ruptured membranes. A system for fetal
      pulse oximetry is used, consisting of monitor Nellcor-N 400; oxygen sensor FS-14
      and printer P-400 (Nellcor Puritan Bennett incorporation). Sensor is applied by
      mean dilatation of cervical channel 6.5 +/- 1.9 cm. Mean duration of monitoring
      of the pregnant woman is 104 +/- 68 minutes, range 30 to 180 min. The time of
      reliable signal quality is 83% for first stage of labour and 70% for second stage
      of labour. Mean SpO2 values are 47.1 +/- 9.8%. The conclusion is made that fetal
      pulse oximetry is an easy method to use, without side effects for mother and
      fetus. Mean SpO2 values are tower than in adults and vary inside wider range 35
      55%.

PMID- 10948625
TI  - [Myoma uteri per magna developing in a girl of 15].

PMID- 10948626
TI  - [Isolated torsion of the fallopian tube in a woman in the postmenopause].

PMID- 10948627
TI  - [A case of a granulosa-cell tumor in a 10-month-old nursing infant].
AB  - A rare case ovarian tumor in a 10-month sibling is presented. The clinical
      picture is dominating with isosexual puberty and me presence of ascites.
      Following laparotomy an ovarian tumor was established with morphological data for
      granulosa cell tumor. The therapeutical schemes are discussed for me ovarian
      tumor treatment and fertility preservation.

PMID- 10948628
TI  - [Dysplasias (CIN, SIL) of the cervix uteri in women].

PMID- 10948629
TI  - [Endometrial cancer: a current therapeutic and diagnostic protocol].
AB  - In the presented methodical scheme, consecutively and systematically are
      scrutinised the epidemiology, the risk factors, the etiopathogenesis, the
      histopathology and the clinical signs of the endometrial cancer. The diagnostic
      possibilities, as well as the staging principles are pointed. The current
      treatment tactics, therapeutic schemes according to the stage and follow-up
      corresponding to the requirements of the oncological doctrine are presented.

PMID- 10948630
TI  - [The use of a subcutaneous implant--25 mg--of 17 beta-estradiol in
      hysterectomized and ovariectomized women. Its effect on lipid metabolism].

PMID- 10948631
TI  - [Gynecological cancer diseases in the cities of Stara Zagora, Sliven, Burgas and
      Iambol].

PMID- 10948632
TI  - [The use of hysterosonography and transvaginal sonography in combination with the
      progesterone test in asymptomatic women in risk groups in the postmenopause].

PMID- 10948633
TI  - [Our experience with the use of Hyaluricht in gynecological practice (preliminary
      report)].

PMID- 10948634
TI  - [Dysmenorrhea in puberty and adolescence].

PMID- 10948635
TI  - [Current diagnostic methods in breast pathology].

PMID- 10948636
TI  - [The 1st successful results of treating patients with clinically significant
      values of sperm antibodies by assisted reproduction methods].

PMID- 10948637
TI  - [Antibodies against Chlamydia and spermatozoa in infertile patients].

PMID- 10948638
TI  - [The new low-dose contraceptive Logest--first impressions].

PMID- 10948639
TI  - [Our experience in using bromocriptine-Richter in gynecology (a preliminary
      report)].

PMID- 10948640
TI  - [Cystectomy during pregnancy].

PMID- 10948641
TI  - [Riselle--an estradiol implant for preventing bone loss after an ovariectomy (a
      pilot study)].

PMID- 10948642
TI  - [An evaluation of the treatment of cervical ectopia using Solcogyn (a randomized
      comparative study with cryotherapy)].

PMID- 10948643
TI  - [From microsurgery to surgical laparoscopy (a review)].

PMID- 10948644
TI  - Web-based medicine.

PMID- 10948645
TI  - Reflections on the War in Korea. Part II.

PMID- 10948646
TI  - Primary gastric lymphoma: a clinicopathological study.
AB  - A retrospective study of 25 patients treated for primary gastric lymphoma was
      made to investigate a number of problems related to treatments and report the
      factors influencing prognosis. In the 5-year-survival rate according to Working
      Formulation classification, either survival rate of low-grade type or
      intermediate-grade type was higher than that of high-grade type. Both the 5-year
      survival rate of cases without lymph node metastasis and that of cases that
      involved perigastric lymph nodes were higher than that of cases that involved
      distant gastric lymph nodes. Those surviving five years after perigastric lymph
      node metastasis had received D3 or D4 dissection and postoperative multicombined
      chemotherapy. Tumors invading only to the submucosal layer had received D2
      dissection and were not treated by postoperative multicombined chemotherapy, and
      recurrence was not recognized in these cases. Of 9 cases infiltrating into the
      musclaris propria or serosa without lymph node metastasis, 8 cases were treated
      by postoperative multicombined chemotherapy and were alive without recurrence,
      but one case without postoperative multicombined chemotherapy died by recurrence.
      Therefore, adequate therapy for gastric lymphoma with infiltrating into
      submucosal layer is gastrectomy with D2 lymph node dissection, and postoperative
      multicombined chemotherapy is not necessary. The cases with perigastric lymph
      node metastasis, or the cases with invading from muscularis propria to serosa
      require D3 or D4 lymph node dissection with postoperative multicombined
      chemotherapy. But the cases with distant gastric lymph node metastasis or
      invading adjacent structure or high-grade type histologically (WF classification)
      require preoperative chemotherapy.

PMID- 10948647
TI  - Study of cholelithiasis after gastrectomy.
AB  - We studied cholelithiasis that occurred after gastrectomy in 52 patients (35
      males and 17 females) encountered at our department between January, 1978 and
      December, 1998. Gastrectomy had been performed for gastric or duodenal ulcer in
      35, gastric cancer in 14, gastroptosis in 2, and gastric trauma in 1 of these
      patients. Reconstruction after gastrectomy was performed by the Billroth II
      method (B-II method) in 31 patients, Billroth I method (B-I method) in 17, Roux
      en-Y method (Roux-Y method) in 3, and esophagogastrostomy in 1. The period
      between gastrectomy and discovery of gallstones was 1-5 years in 9, 5-10 years in
      10, and 10 years or longer in 33, or more than 60% of the patients. Gallstones
      were present in the gallbladder alone in 33, bile duct alone in 9, gallbladder
      and bile duct in 10; the percentage of bile duct stones was high. The type of
      stones was bilirubin-calcium stones in 21, black stones in 12, pure cholesterol
      stones in 1, combined stones in 4, mixed stones in 12, and others in 2; pigment
      stones accounted for 63.5%. Gallstones were symptomatic in 78.8% of the patients,
      and abdominal pain was the most frequent symptom. Bile was positive on bacterial
      culture in 68.4%, and Gram-negative bacilli were the most frequently isolated.
      Lymph node dissection, vagotomy, cholestasis, and biliary tract infection are
      considered to be related to cholelithiasis after gastrectomy.

PMID- 10948648
TI  - Diagnosis of intrarenal reflux and its role in pathogenesis of reflux nephropathy
      in children.
AB  - We compared newly developed radionuclide cystography with conventional contrast
      voiding cystography (VCG) with regard to their diagnostic usefulness of
      intrarenal reflux (IRR) in children. Based on the imaging findings, we assessed
      the role of IRR in the pathogenesis of reflux nephropathy (RN). Among the ureters
      which revealed IRR diagnosed by radionuclide cystography, 38.9% (7 out of 18
      ureters) of the cases examined by VCG had IRR. In the case of VCG, the
      sensitivity and specificity of IRR detection were 33.3% and 100%, respectively.
      There was a statistical correlation between the presence/absence of IRR and
      vesicoureteral reflux (VUR). RN was significantly correlated with advanced grade
      of VUR associated with IRR. Among 9 kidneys of the subjects who had suffered from
      urinary tract infection (UTI) only once, IRR was detected in 33.3% (3/9) and RN
      in 66.7% (2/3). From these findings, conventional contrast VCG is considered not
      effective for the diagnosis of IRR. Moreover, it is suggested that VUR
      complicated with IRR is deeply associated with the development of RN. In
      addition, it is suggested that UTI might be related to the onset of IRR.

PMID- 10948649
TI  - Establishment of an osteoblastic osteosarcoma cell line and effects of cell
      culture conditions on secretion of matrix metalloproteinases from the cultured
      osteosarcoma cells.
AB  - Osteosarcoma cells are useful for investigating bone metabolism as malignant
      counterpart of osteoblasts. In hematogenous metastases of osteosarcoma cells, the
      cells need to adjust to various changes in pericellular environment. The changes
      in pericellular environment may change intracellular environment and consequently
      the secretion of matrix metalloproteinases (MMPs) which destroy extracellular
      matrices. In this report, a new cell line, KOS-1, derived from human osteoblastic
      osteosarcoma was established, and we assumed various culture conditions
      containing ingredients of the extracellular matrix to make a comparative study on
      MMPs detected from the culture supernatants. A wide spectrum of MMPs, including
      MMP-1 and -3 which were increased in the presence of interleukin 1 beta, was
      detected in this cell line. Production of MMP-1, the enzyme which decomposes
      types I, II, III and X collagen, by the cells, was increased in the presence of
      type I collagen. MMP-3 (stromelysin-1) which degrades types III and IV collagen,
      laminin, fibronectin, proteoglycan, etc. was produced more abundantly in the
      presence of type IV collagen. MMP-2 (72-kd type IV collagenase/gelatinase A)
      activity was found to be increased in the presence of gelatin and type IV
      collagen. The MMPs production in cultured osteosarcoma cells was changed
      depending on the culture conditions. This indicates that the same osteosarocma
      cells produce different amounts and kinds of enzymes involved in local
      infiltration and remote metastases and increase the production of the enzymes
      most required under a specific environment.

PMID- 10948650
TI  - Apoptosis in giant cell tumors of bone.
AB  - Although giant cell tumor of bone (GCT) is characterized by the extensive
      multinucleated giant cells among mononuclear stromal cells, proliferation of
      these cells and multinucleation are not without limit in certain cases. Few
      studies on oncogenesis of GCT have focused on the negative growth control,
      including growth arrest and apoptosis. The purpose of this study was to
      investigate the mechanism of cell death in multinucleated giant cells and stromal
      cells of GCT. In this study, we have demonstrated that GCT cells can undergo
      apoptosis. The cells in surgical specimen were positively stained in situ nick
      end labeling methods, and electron micrographs showed the morphological changes
      associated with apoptosis in some of stromal cells and multinucleated giant
      cells. A candidate responsible for this apoptosis was then examined using
      cultured GCT cells. We focused on Fas that is a major trigger of apoptosis.
      Cultured GCT cells expressed detectable amount of Fas on their surface. Although
      GCT cells did a little undergo apoptosis following treatment with anti-Fas alone,
      combination treatment with cyclohexamide led to an increase in apoptosis of the
      GCT cells. These data suggested that the sensitizing activity of cyclohexamide on
      anti-Fas mediated cytotoxicity could happen in vitro.

PMID- 10948651
TI  - Expansive laminoplasty by sagittal splitting of the spinous process for cervical
      myelopathy: correlation of clinical results with morphological changes in the
      cervical spine.
AB  - Morphological changes in the cervical spine were evaluated using radiography in
      140 patients with cervical myelopathy who underwent expansive laminoplasty by
      sagittal splitting of the spinous process. We assessed the influence of these
      observed changes on the postoperative clinical results. The mean follow-up period
      was 33 +/- 19 months. Intervertebral body union occurred in 18%, and interlaminal
      union in 80% of the patients. The factors influencing the bony union in these
      were not identified. Bony union did not significantly influence the clinical
      results. There were changes in cervical alignment in 29 (21%) patients after the
      operation. Correlation between the spinal curvature and the clinical results was
      the strongest for the sigmoid-type curvature. The number of patients in whom
      preoperative ROM was maintained was only 8 (7%). The range of cervical spine
      motion decreased by approximately 50%, and there was no correlation with the
      clinical results. The surgical method described in the current study for
      compression myelopathy was associated with postoperative morphological changes
      and decreased ROM in the cervical spine, but nonetheless provided good
      postoperative results unless extreme morphological abnormalities occurred. This
      surgical technique was safe and gave satisfactory results in patients with
      preoperative morphological abnormalities in the cervical spine.

PMID- 10948652
TI  - Factors associated with osteonecrosis in the femoral head in chronic alcoholism.
AB  - While alcohol abuse is a possible etiologic factor in osteonecrosis in the
      femoral head (ON), the relationship between alcoholic liver dysfunction and ON is
      uncertain. Among 336 patients with alcoholic liver dysfunction who had
      radiographic examination of the hip at two hospitals for alcohol abuse treatment
      in southern Japan, the records for 291 men and 1 woman (mean age, 47.8 years;
      range, 24 to 72 years) had adequate information available concerning daily and
      cumulative alcohol intake, duration of intake, serum concentrations of liver
      enzymes, and platelet count. These variables were investigated for any
      correlation between the 8 patients with radiographic evidence of ON and the 284
      without. Liver biopsy was performed in 223 patients. Except for alanine
      aminotransferase, liver enzyme concentrations were significantly lower in
      patients with ON than in those without. Histologically, 2 patients with ON were
      diagnosed with cirrhosis; 1 with pre-cirrhotic changes; and 2 with fibrosis.
      These results suggested that ON occurred in the late stages of liver disease when
      serum enzyme concentrations had returned to normal or were only mildly elevated.

PMID- 10948653
TI  - Molecular cloning and characterization of chick CD9.
AB  - CD9 is a tetra-membrane-spanning glycoprotein involved in cell adhesion,
      migration, growth signaling and tumor cell metastasis. In this study a CD9 cDNA
      clone has been isolated from chick cDNA library. The chick CD9 clone contains an
      open reading frame of 224 amino acids. The deduced amino acid sequence from chick
      CD9 shows 63.3% identity with the human counterpart. Human and monkey CD9
      upregulate the diphtheria toxin (DT) binding activity of human heparin-binding
      EGF-like growth factor, while chick CD9 lacks the ability to upregulate the DT
      binding activity. Comparison of the amino acid sequence of chick CD9 with that of
      human CD9 gives a clue to understanding the upregulation mechanism.

PMID- 10948654
TI  - Latent multiple infections by herpes simplex virus type 1.
AB  - Viral strains obtained during the same period which were asymptomatically shed
      into the saliva of patients with oral cancer after surgery or isolated from the
      focus of patients with herpes simplex virus type 1 (HSV-1) infection after first
      visit to hospital were analyzed using molecular epidemiology. There were 10
      subjects in each group. Viral strains used were from 3 to 5 strains (mean: 3.4
      strains) in the malignant patients and from 3 to 8 strains (mean: 5 strains) in
      the herpetic patients. One of 10 patients with oral cancer showed a different DNA
      cleavage pattern in viral strains shed into saliva at the last day. In 10
      patients with HSV-1 infection, all viral strains in each of the cases showed
      identical DNA cleavage patterns. These results suggested the existence of a
      latent multiple infection and a simultaneous reactivation of HSV-1.

PMID- 10948655
TI  - Schwannoma in the sigmoid colon: report of a case.
AB  - Schwann cell tumor occurring in the intestines is rare. A 68-year-old female came
      to our hospital because of hematemesis. Barium enema and colonoscopic examination
      revealed submucosal tumor in the sigmoid colon. Laboratory data showed mild
      anemia. No other abnormal finding was found in the blood chemistry. Tumor marker
      levels of carcinoembryonic antigen (CEA), CA19-9, alpha feto protein (AFP) and
      neuron specific enolase (NSE) were within normal limits. The exploratory
      laparotomy confirmed a large sigmoid colon tumor. She received sigmoid colectomy.
      The resected specimen was a submucosal tumor with central depression, measuring
      4.7 x 3.5 x 3.0 cm in size. The cut surface of the tumor was yellowish hue with
      necrosis. Histological examination showed spindle-shaped tumor cells with
      palisading comma-shaped nuclei and the nuclear pleomorphism. Immunohistochemical
      examination revealed that the tumor was positive for S-100 protein staining, and
      negative for Actin and for H.H.F. staining. These findings showed that this tumor
      was of Schwann cell origin. We report here the case in detail of a schwannoma in
      the sigmoid colon.

PMID- 10948656
TI  - A case of synchronous double cancers of the pancreas and stomach.
AB  - Pancreatic cancer carries a poor prognosis, especially invasive ductal carcinoma
      of the pancreas. We present here the case of a 76-year-old man who developed
      synchronous double cancers of the stomach and pancreas. He was referred to our
      hospital in December, 1997, with a provisional diagnosis of carcinoma of the
      stomach. Laboratory data on admission showed normal levels except for the serum
      carcinoembryonic antigen level. Abdominal ultrasonography revealed a low echoic
      mass anterior to the pancreas, suggestive of a nodal metastasis. Intraoperative
      histological findings from the pancreatic nodule confirmed a primary pancreatic
      cancer. The diagnosis of double cancers of the stomach and pancreas was made, and
      subtotal gastrectomy and distal pancreatectomy with lymph nodes dissection were
      carried out. The histologic sections from the stomach showed a moderately
      differentiated tubular adenocarcinoma, whereas those from the pancreas showed a
      well to moderately differentiated tubular adenocarcinoma. Double carcinomas in
      this association are relatively rare.

PMID- 10948657
TI  - Coronary artery bypass surgery in a patient with myasthenia gravis.
AB  - A 73-year-old man with myasthenia gravis required quadruple coronary artery
      bypass grafting due to triple-vessel disease. Anesthetic management was performed
      with general anesthesia using a reduced dose of muscle relaxant with the aid of a
      neuromuscular transmission monitor. He was extubated 14 hrs after surgery without
      difficulty under this monitor. His postoperative course was uneventful. A patient
      with myasthenia gravis who required coronary artery bypass surgery was
      successfully performed by the deliberate preoperative evaluation of patient's
      myasthenic and cardiac status, and by the careful perioperative management.

PMID- 10948658
TI  - Unresectable advanced gastric cancer effectively treated by combined chemo
      immunotherapy: a report of two cases.
AB  - We have experienced two cases of unresectable advanced gastric cancer effectively
      treated by chemo-immunotherapy. One case was of a 68-year-old male patient
      diagnosed as having inoperable advanced gastric cancer with liver and lung
      metastasis. This patient was treated by combined chemo-immunotherapy of MMC 10
      mg/M, 5'-DFUR 800 mg/day and OK-432 5 KE/2W. At 6 months later, a computed
      tomography (CT) scan and upper gastrointestinal (GI) series revealed that the
      metastatic liver tumors and stomach lesion were remarkably decreased in size, and
      endoscopic biopsy confirmed no cancer cells in the stomach lesion. Moreover, the
      metastatic lung tumor had disappeared on chest X-ray. The other case was of a 68
      year-old female patient with unresectable advanced gastric cancer treated by
      combined administration of MMC 10 mg/M, 5-FU 200 mg/day and OK-432 5 KE/2W. At 2
      months after commencing the treatment, there was a reduction in the serum
      carcinoembryonal antigen (CEA) level. At 6 months later, the CEA had decreased to
      normal, the primary and metastatic sites had completely disappeared on CT, and
      endoscopic biopsy confirmed no cancer cells in the stomach lesion. This patient
      has survived to date for 5 years and 6 months after commencing the treatment.
      These results suggested that combined chemo-immunotherapy of MMC, antimetabolite,
      and OK-432 was an effective treatment for unresectable advanced gastric cancer.

PMID- 10948659
TI  - Two cases of biliary hemorrhage after percutaneous transhepatic biliary drainage
      in which transcatheter arterial embolization was effective.
AB  - Patient No. 1 was a 66-year-old male who was diagnosed as having cancer of the
      caput pancreatis, and underwent percutaneous transhepatic biliary drainage
      (PTBD). Since the tube slipped out, percutaneous transhepatic gallbladder
      drainage (PTGBD) was performed. After PTGBD, biliary hemorrhage was observed for
      two to three days, then hemorrhage disappeared and bile flowed smoothly. Since
      the tube was likely to slip out, the tube was replaced. After replacement of the
      tube, biliary hemorrhage was noted for two to three days, then spontaneously
      subsided again. After icterus was reduced, pancreatoduodenectomy was performed.
      During surgery, a number of massive blood clots were noted in the bile duct. The
      PTGBD tube was removed, and a transjejunal tube was placed. On the 11th day after
      the surgery, hemorrhage occurred in the bile duct tube, and the patient went into
      shock. Emergency abdominal angiography was performed. A false aneurysm was
      detected in A6 and embolized using a microcoil. After transcatheter arterial
      embolization (TAE), hemorrhage stopped, and the patient was discharged. Patient
      No. 2 was a 68-year-old male who was diagnosed as having cholelithiasis and
      underwent PTBD. On the 21st day after PTBD, biliary hemorrhage occurred and the
      patient fell in shock status. Emergency abdominal angiography was performed. A
      false aneurysm was detected in A3 and embolized using a microcoil. After TAE,
      cholangioscopic lithectomy was performed and the disease alleviated. Thereafter
      the patient was discharged. It is necessary to consider false aneurysm when
      biliary hemorrhage occurs after PT(G)BD.

PMID- 10948660
TI  - An anomalous case of the hepato-spleno-mesenteric and the gastro-phrenic trunks
      independently arising from the abdominal aorta.
AB  - This report describes an arterial anomaly case in the celiaco-mesenteric region,
      which was encountered in a Japanese male cadaver in the dissecting room at Kurume
      University School of Medicine in 1999. In this case, the usual celiac trunk was
      not identified, and the hepato-spleno-mesenteric and the gastro-phrenic trunks
      were independently arising from the abdominal aorta. In addition, the common
      hepatic artery divided into the left hepatic, the right hepatic, and the
      gastroduodenal arteries simultaneously, then, the accessory gastric artery arose
      from the left hepatic artery. This type of arteral anomaly belongs to the Type
      III of Adachi's classification and the Type II of Morita's classification.

PMID- 10948661
TI  - Relationship between degree of nonspecific hyperresponsiveness and number of
      positive skin tests in asthmatics.
AB  - Bronchial hyperresponsiveness (BHR) is a typical feature of asthma, and is, at
      least in part, related to the chronic inflammation. Allergen exposure is a major
      trigger and cause of allergic inflammation. The possible relationship between the
      degree of bronchial reactivity and the number of positive skin test was studied.
      One hundred and one patients with allergic asthma (and rhinitis) underwent skin
      prick tests and methacholine bronchial challenge according to standard protocols.
      No significant relation was found between the degree of BHR and age or sex.
      Conversely, it was found that the number of positive skin tests correlated well
      with the degree of BHR (p = 0.046); in particular, those patients with three or
      more sensitivities showed greater bronchial reactivity. The present data support
      the hypothesis that allergic polysensitized patients may exhibit greater
      bronchial hyperresponsiveness, possibly due to an enhanced inflammatory component
      related to the exposure to multiple allergens.

PMID- 10948662
TI  - Validation of a new technique to assess exhaled hydrogen peroxide: results from
      normals and COPD patients.
AB  - Chronic airways inflammation in chronic obstructive pulmonary disease (COPD)
      induces the activation of several cell types with delivery of proteases and
      reactive oxygen species (ROS). Assessing oxidant content in the exhaled air of
      COPD patients has proven useful in monitoring airway inflammation. The present
      study was designed to confirm the usefulness of exhaled hydrogen peroxide
      concentration determination in COPD patients using a new technique which allows
      longer storage of the expired air condensate before the H2O2 assay. The technique
      was applied in 13 healthy nonsmoking subjects (six male, age range 22-40 yrs) and
      in seven patients (five male, age range 58-81 yrs) with mild or moderate COPD.
      Subjects breathed into a one-valve mouthpiece, and the exhaled air was directed
      into a vial kept at 0 degree C. After approximately 15 min of quiet breathing, 1
      mL of expired air condensate was collected. An aliquot, 450 microL, of this
      sample was immediately added to an equal volume of a reaction mixture containing
      2 mM 3,5,3',5'-tetramethylbenzidine and 40 microL of enzyme stock solution (0.5
      mg.mL-1). After 15 min, 45 microL sulphuric acid was added (1 N final
      concentration), resulting in a reaction mixture pH of 1.0. After a further 10-min
      incubation, H2O2 concentration determination was performed spectrophotometrically
      at 450 nm. This solution, as well as the H2O2 assay, was stable for > or = 24 h
      if the sample was kept in the dark and at 4 degrees C. There was high stability
      on repeated measures, with a coefficient of variation equal to zero. The mean +/-
      SD H2O2 level in exhaled air from normal subjects was 0.12 +/- 0.09 microM,
      whereas it was significantly increased in COPD patients (0.50 +/- 0.11 microM; p
      = 0.0001 compared to healthy subjects). In three healthy control subjects, a
      normal H2O2 level in expired air increased to 0.70-0.80 microM during an acute
      upper respiratory tract infection. This new technique of hydrogen peroxide assay
      in expired air condensate greatly minimizes the inaccuracy deriving from the
      instability of hydrogen peroxide. The preliminary results obtained using this
      technique provide direct evidence for increased reactive oxygen species
      production in the airways of stable chronic obstructive pulmonary disease
      patients. However, the specificity of the procedure could be reduced by the
      interference of upper respiratory tract infections.

PMID- 10948663
TI  - Prevalence of chronic bronchitis and associated risk factors in a rural area of
      Kayseri, Central Anatolia, Turkey.
AB  - This population-based cross-sectional survey was carried out to determine the
      prevalence of chronic bronchitis and associated risk factors in a rural area of
      Kayseri, Central Anatolia, Turkey. Subjects (1,023) aged 20-83 yrs (81.8% of
      eligible subjects) were interviewed using a modified version of the adult
      questionnaire compiled by the European Community Respiratory Health Survey.
      Subjects with "presence of cough and phlegm on most days during at least three
      months per year for at least the two previous years" were classified as having
      chronic bronchitis. According to the criteria used, 138 (13.5%) were classified
      as having chronic bronchitis. The prevalence was higher in males (17.8%) than
      females (10.0%). There was no overall significant association between chronic
      bronchitis and age in males, but, in females, the difference between age groups
      was important. There was no association between chronic bronchitis and family
      income, although the prevalence was highest in the low-income group. Subjects who
      reported childhood respiratory illnesses had a 1.7-fold increased risk of chronic
      bronchitis compared to those without such a history. The prevalence was much
      higher among people exposed to biomass fuel combustion and among smokers and
      exsmokers than among nonsmokers. In multivariate analyses, a significant increase
      in the prevalence of chronic bronchitis was seen in males, those who had received
      poor schooling, those reporting childhood respiratory illnesses, and those
      exposed to biomass fuel combustion and according to smoking habit.

PMID- 10948664
TI  - Tobacco smoking, occupational exposure and chronic respiratory disease in an
      Italian industrial area.
AB  - Tobacco smoking and occupational exposure are the major factors responsible for
      chronic obstructive pulmonary disease (COPD) worldwide. The prevalence of this
      disease and its main risk factors were investigated in an area characterized by a
      high density of iron- and steelworking factories in North Italy. A total of 1,497
      subjects (50% male) aged 40-59 yrs underwent an interview and a physical
      assessment, and 1,244 of them also underwent spirometry. The prevalences of COPD
      and asthma were 16.1 and 5.2% among males and 4.4 and 4.0% among females. COPD
      and respiratory symptoms were associated with both smoking and occupational
      exposure in males: the odds ratios for having been occupationally exposed among
      males were 2.3 (95% confidence interval 1.4-3.7) for COPD and 1.7 (1.2-2.6) for
      respiratory symptoms. No association was found between asthma and tobacco smoking
      or occupational exposure. The forced expiratory volume in one second and forced
      vital capacity were associated negatively with smoking and not associated with
      occupational exposure. In females, lesser effects of cigarette smoking on both
      self-reported respiratory diseases and lung function tests were found. The
      attributable risks of chronic obstructive pulmonary disease for smoking and
      occupational exposure among males were 52.9 and 8.8%, respectively, and 60.3%
      when considered together, whereas 18.8% of chronic obstructive pulmonary disease
      cases among females were attributable to smoking.

PMID- 10948665
TI  - Chronic obstructive pulmonary disease management among primary healthcare
      physicians.
AB  - The aim of this study was to evaluate the dissemination of chronic obstructive
      pulmonary disease (COPD) management guidelines among primary healthcare
      physicians in Greece. One hundred and five of 120 (87.5% response rate) completed
      a questionnaire about COPD morbidity and management. One in eight patients
      examined by a primary care physician suffered from COPD. Forty-eight physicians
      treated their COPD patients according to the pulmonologist's recommendations and
      69 according to COPD management guidelines. All the physicians encouraged and
      supported their COPD patients in stopping smoking, but continuous abstinence was
      low. The most commonly prescribed drugs were beta 2-agonist inhalers (14.8%),
      corticosteroid inhalers (13.47%), antibiotics (12.6%) and influenza vaccines
      (12.6%). The most commonly prescribed antibiotics were cephalosporins (33.72%),
      macrolides (27.71%) and amoxycillin plus clavulanic acid (25.3%). According to
      the present study, chronic obstructive pulmonary disease management among primary
      healthcare physicians was not in total accordance with current guidelines. Better
      dissemination of chronic obstructive pulmonary disease guidelines among
      specialists and primary healthcare physicians will hopefully make chronic
      obstructive pulmonary disease management in outpatients optimal.

PMID- 10948666
TI  - Pott's disease of the lower cervical spine in a diabetic patient.
AB  - Over the last few years, tuberculosis has steadily been returning to the worlds
      attention as a major health threat. The spinal localization of tuberculosis
      (Pott's Disease) represents around 1% of the case histories, in 3-5% of which
      there is cervical involvement. Diabetes mellitus increases the risk of infectious
      disease and predisposes to tuberculosis. Here, a rare case is presented of Pott's
      disease in the lower cervical spine, associated with retropharyngeal abscess in a
      diabetic patient. The aim of this study is to emphasize the importance of early
      diagnosis in such patients, so that adequate pharmacological and/or surgical
      treatment can be initiated to avoid serious complications.

PMID- 10948667
TI  - Eosinophilic granuloma of the lung presenting as an endobronchial mass.
AB  - A 19-yr-old male presented with left lung parahilar consolidation and clinical
      signs of pneumonia. These symptoms were secondary to an endobronchial mass in the
      apical segment of the lower lobe. At thoracotomy an apical segment bronchial
      sleeve resection successfully extirpated what later proved to be an endobronchial
      eosinophilic granuloma. To the authors' knowledge this is the first case report
      of an endobronchial eosinophilic granuloma in an adult.

PMID- 10948668
TI  - Transudative right pleural effusion due to compression of the brachiocephalic
      vein caused by an intrathoracic goitre.
AB  - The case presented in this report is of a female patient who suffered recurrent
      transudative right pleural effusions, due to a giant benign intrathoracic goitre.
      The latter caused compression of the brachiocephalic vein, which is a very rare
      cause of pleural fluid accumulation. Magnetic resonance imaging played a crucial
      diagnostic role.

PMID- 10948669
TI  - Detection of Mycobacterium tuberculosis in bronchial washing of smear-positive
      patients after sputum conversion.
AB  - The main purpose of chemotherapy of tuberculosis is to ensure the
      noninfectiousness of patients with active pulmonary tuberculosis. For this
      reason, the sputum of smear-positive pulmonary tuberculosis patients is examined
      at the end of the first and second month of therapy to determine the conversion
      rate, which is expected to be 85% at the end of the second month. The patients
      whose sputum has converted to smear-negative are considered noninfectious. The
      aim of this study was to challenge the theory that negative sputum smear test
      results always indicate the absence of Mycobacterium tuberculosis bacilli in
      respiratory secretions from patients with active pulmonary tuberculosis after
      treatment. In order to achieve this goal, 46 patients with pulmonary tuberculosis
      whose sputum was positive for M. tuberculosis at the first visit were followed
      until they gave two consecutive negative smears. The bronchoalveolar lavage fluid
      of these patients was then examined for M. tuberculosis bacilli. It was observed
      that eight (17.5%) and five (10%) of these patients, who had already undergone
      sputum conversion, gave positive smear and culture results respectively. It could
      be concluded that a negative sputum result is not an appropriate index for
      evaluating the infectiousness of patients with pulmonary tuberculosis, and, since
      a few Mycobacterium tuberculosis bacilli can cause tuberculosis, especially in an
      immunocompromised host, it is mandatory that complementary studies to assess the
      transmission and virulence of Mycobacterium tuberculosis bacilli after sputum
      conversion be conducted.

PMID- 10948670
TI  - Health-related quality of life, psychological adjustment and compliance to
      treatment in patients on domiciliary liquid oxygen.
AB  - The purpose of this study was to investigate the effects of two different aspects
      of compliance with liquid oxygen (LOX) therapy on quality of life and to explore
      possible pulmonary and psychosocial concomitants. The study sample consisted of
      57 oxygen-dependent patients with chronic obstructive pulmonary disease under LOX
      therapy. Compliance was defined as continuous oxygen use as prescribed and also
      as readiness to use LOX outdoors. The study design encompassed three major
      measuring points, the first of which was an initial assessment, the second 3
      months later and the third follow-up after 14 months. Furthermore, during the
      course of the study, two telephone interviews were conducted. The psychosocial
      variables studied included quality of life, psychological adjustment and two
      different aspects of compliance with LOX therapy. Seven (12%) patients used LOX
      less than prescribed and 13 (23%) refused to use LOX away from home. Those
      patients who used LOX insufficiently had a significantly lower life-satisfaction
      than those who were compliant (p = 0.02). The discriminance analysis included
      several psychosocial variables discriminating between both groups, allowing the
      correct classification of 85% of the patients who used LOX as prescribed and 83%
      of the noncompliant patients (p = 0.01). At follow-up, the data of 25 patients
      were available. Of these, five refused outdoor LOX use. Their quality of life was
      significantly worse in almost all areas examined as compared to the outdoor LOX
      users (p < 0.05, respectively). Compliance is an essential prerequisite for the
      beneficial effects of liquid oxygen on quality of life. Because psychological
      factors influence adherence to liquid oxygen therapy, patients should receive
      individual psychological counselling and training before transfer to liquid
      oxygen therapy.

PMID- 10948671
TI  - Dendritic cells: pulmonary immune regulation and asthma.
AB  - Dendritic cells (DCs) may play a pivotal role in the initiation and establishment
      of chronic T-helper cell (Th)-2 mediated lung inflammation as seen in asthma.
      Current in vitro data indicate that the haemopoietic lineage of the DC or the
      local environment in which a DC matures, or both acting together, can instruct
      the DC to become a Th1- or Th2-inducing antigen-presenting cell. Once allergen
      specific Th2 memory cells are drawn into the lung, repeated allergen presentation
      by lung DCs may drive the persistent stimulation of allergen-specific memory Th2
      cells and precipitate a state of chronic inflammation that contributes to the
      remodelling and hyperreactive airways that characterize asthma. In addition, the
      persistent stimulation of effector Th2 cells and the subsequent Th2 cytokine
      secretion can create a Th2 cytokine milieu in the lung that may influence the
      differentiation of antigen-specific Th0 in the lung and naive Th in the lung
      associated lymph nodes to develop into Th2 effector cells. Immunoglobulin E
      receptors on antigen-presenting cells may facilitate chronic T-helper cell-2
      inflammation directly by focusing allergen to dendritic cells for uptake and
      indirectly by stimulating alveolar macrophages to secrete mediators that lead to
      the maturation of dendritic cells with a low capacity to secrete interleukin-12.

PMID- 10948672
TI  - Potential role of macrolides in the treatment of asthma.
AB  - A body of evidence highlights the fact that macrolides may not only enhance the
      host defence system through increased cytokine synthesis by host cells but also
      exhibit anti-inflammatory activity by including anti-inflammatory cytokines.
      Several authors have stressed the possibility that macrolides are useful in the
      treatment of asthma because of their antimicrobial activity rather than any anti
      inflammatory action. However, the mechanism of action of macrolides in improving
      asthma and reducing airway responsiveness is speculated not to be due to their
      antibiotic properties, especially when these agents are active in noninfectious
      asthma. The steroid-sparing effect of macrolide antibiotics has been postulated
      to contribute to their beneficial actions in the treatment of asthma.
      Nevertheless, a number of studies have shown that macrolides antibiotics have an
      anti-inflammatory effect which is independent of their antibiotic action or any
      influence on corticosteroid metabolism. Macrolides may be useful in the treatment
      of patients with steroid-dependent asthma, probably because they inhibit
      eosinophilic inflammation. It has also been suggested that the effect of
      macrolides on bronchial hyperresponsiveness is mediated by their inhibitory
      action on superoxide production and chemotaxis of polymorphonuclear neutrophils
      and the mixed lymphocyte reaction. In any case, it is clear that the mechanism of
      action of macrolides in asthmatic syndrome is not unequivocal. Only well-designed
      and -conducted clinical studies are capable of assessing the efficacy and safety
      of immunosuppressive macrolides in the treatment of asthma.

PMID- 10948673
TI  - Nasal ventilation in progressive neuromuscular disease: experience in adults and
      adolescents.
AB  - A nihilistic approach to ventilatory support in progressive neuromuscular
      disorders is no longer acceptable. Noninvasive ventilation may improve survival
      and quality of life in some patients. In other situations, worthwhile palliation
      of symptoms of nocturnal hypoventilation and dyspnoea may be achieved.
      Noninvasive ventilation combined with cough assistance may obviate the need for
      tracheostomy ventilation, or can be employed as part of a staged approach.
      Individual titration of ventilatory support to meet the needs of the individual
      and family is vital. The participation of the patient, family and carers in
      decision-making is crucial and advanced directives are likely to be used
      increasingly.

PMID- 10948674
TI  - Exercise and noninvasive ventilatory support.
AB  - Breathlessness is the most common symptom that limits exercise in patients with
      chronic obstructive pulmonary disease and who may receive benefit from exercise
      training programmes. Exercise intensity may influence the physiological benefits
      of the programme. Although the exact underlying physiopathological mechanism is
      still unclear, there is laboratory evidence that continuous positive airway
      pressure and other modalities of mechanical ventilation (delivered either by
      mouthpiece or facial or nasal masks) may reduce breathlessness and increase
      exercise tolerance in these patients, in order to allow them to reach a higher
      exercise intensity. Respiratory muscle unloading and a reduction in intrinsic
      positive end-expiratory pressure have been considered among the potential
      mechanisms underlying these effects. The role of mechanical ventilation in
      pulmonary rehabilitation programmes, if any, is still to be defined.

PMID- 10948675
TI  - Reference values for bronchoalveolar lavage in children.
AB  - Bronchoalveolar lavage (BAL) is a well-established diagnostic tool for the
      assessment of pulmonary diseases in adults. How BAL contributes to the diagnostic
      process in childhood lung diseases is less clear. One of the problems in
      interpreting BAL findings in children is that there are few reference data for
      BAL fluid constituents in children. This report addresses some of the technical
      problems of bronchoalveolar lavage in children and summarizes current knowledge
      on cellular and noncellular bronchoalveolar lavage fluid components in children
      without lung disease.

PMID- 10948676
TI  - Promotion of respiratory health in utero and during infancy.
AB  - The antenatal period and infancy are critical times for lung growth; hence
      insults to the foetus and young child may have severe and chronic effects on
      respiratory function. This is highlighted by review of the morbidity associated
      with parental smoking, respiratory syncytial virus infection, premature birth and
      invasive antenatal procedures. Promotion of respiratory health in utero and
      during infancy is possible by avoidance of such insults. This requires effective
      education about factors which impact on respiratory health, ongoing research to
      reduce the number of premature births and their complications, and careful
      assessment of the effect of all strategies on long-term pulmonary outcome, so
      that those which impinge unfavourably are not pursued.

PMID- 10948677
TI  - Molecular mechanisms of corticosteroid actions.
AB  - Corticosteroids are the most effective therapy for the treatment of inflammatory
      diseases such as asthma. Functionally, they act partly by inducing anti
      inflammatory genes such as secretary leukocyte proteinase inhibitor, Lipocortin-1
      and interleukin-1 receptor antagonist, but mainly by repression of inflammatory
      genes, such as cytokines, adhesion molecules, inflammatory enzymes and receptors.
      They act by binding to a cytosolic glucocorticoid receptor (GR), which upon
      binding is activated and rapidly translocates to the nucleus. Within the nucleus,
      the GR either induces gene transcription by binding to specific deoxyribonucleic
      acid elements in the promoter/enhancer regions of responsive genes or reduces
      gene transcription by transrepression. The GR reduces gene transcription by
      interaction with pro-inflammatory transcription factors such as activation
      protein-1 and nuclear factor-kappa B. These effects of the GR on gene expression
      involve changes in the chromatin structure localized to the promoter sites of
      responsive genes. Many of the detrimental side-effects of corticosteroids are
      believed to be due to gene induction, leading to the search for novel
      corticosteroids which can repress inflammatory genes without inducing gene
      transcription.

PMID- 10948678
TI  - The Canadian health care system.

PMID- 10948679
TI  - Acetabular revision arthroplasty.

PMID- 10948681
TI  - Soft-tissue images. Mediastinal goitre.

PMID- 10948680
TI  - Surgical residents as teachers.

PMID- 10948683
TI  - Soft-tissue case 34. Rectus sheath hematoma.

PMID- 10948682
TI  - Musculoskeletal images. Migration of the patellar component causing popliteal
      artery occlusion.

PMID- 10948684
TI  - Musculoskeletal case 11. Ruptured Baker's cyst producing a pseudothrombophlebitis
      syndrome.

PMID- 10948685
TI  - Closed tibial shaft fractures: management and treatment complications. A review
      of the prospective literature.
AB  - OBJECTIVE: To compare the results and complications of the various modalities for
      treating closed fractures of the tibial shaft described in the prospective
      literature. DATA SOURCES: A MEDLINE search of the English language literature
      from 1966 to 1999 was conducted using the MeSH heading "tibial fractures."
      Studies pertaining to the management of closed tibial shaft fractures were
      reviewed, and their reference lists were searched for additional articles. STUDY
      SELECTION: An analysis of the relevant prospective, randomized controlled trials
      was performed. Studies including confounding data on open fractures or fractures
      in children were excluded. The 13 remaining studies were reviewed. DATA
      EXTRACTION: Raw data were extracted and pooled for each method of treatment. DATA
      SYNTHESIS: The 13 studies described 895 tibial shaft fractures treated by
      application of a plaster cast, fixation with plate and screws, and reamed or
      unreamed intramedullary nailing. Although definitions varied, the combined
      incidence of delayed and nonunion was lower with operative treatment (2.6% with
      plate fixation, 8.0% with reamed nailing and 16.7% with unreamed nailing) than
      with closed treatment (17.2%). The incidence of malunion was similarly lower with
      operative treatment (0% with plate fixation, 3.2% with reamed nailing and 11.8%
      with unreamed nailing) than with closed treatment (31.7%). Superficial infection
      was most common with plate fixation (9.0%) compared with 2.9% for reamed nailing,
      0.5% for unreamed nailing and 0% for closed treatment. The incidence of
      osteomyelitis was similar for all groups. Rates of reoperation ranged from 4.7%
      to 23.1%. CONCLUSIONS: All forms of treatment for tibial shaft fractures are
      associated with complications. A knowledge of the incidence of each complication
      facilitates the consent process. To fully resolve the controversy as to the best
      method of treatment, a large, randomized, controlled trial is required. This
      review more precisely predicts the expected incidence of complications, allowing
      the numbers of required patients to be more accurately determined for future
      randomized controlled studies.

PMID- 10948686
TI  - An approach to ventilation in acute respiratory distress syndrome.
AB  - Appropriate management of patients with acute respiratory distress syndrome
      (ARDS) represents a challenge for physicians working in the critical care
      environment. Significant advances have been made in understanding the
      pathophysiology of ARDS. There is also an increasing appreciation of the role of
      ventilator-induced lung injury (VILI). VILI is most likely related to several
      different aspects of ventilator management: barotrauma due to high peak airway
      pressures, lung overdistension or volutrauma due to high transpulmonary
      pressures, alveolar membrane damage due to insufficient positive end expiratory
      pressure levels and oxygen-related cell toxicity. Various lung protective
      strategies have been suggested to minimize the damage caused by conventional
      modes of ventilation. These include the use of pressure- and volume-limited
      ventilation, the use of the prone position in the management of ARDS, and
      extracorporeal methods of oxygen delivery and carbon dioxide removal. Although
      the death rate resulting from ARDS has been declining over the past 10 years,
      there is no evidence that any specific treatment or change in approach to
      ventilation is the cause of this improved survival.

PMID- 10948687
TI  - Cementless acetabular revision arthroplasty.
AB  - OBJECTIVE: To evaluate the effects of clinical factors on outcome after
      acetabular revision with a cementless beaded cup. DESIGN: Retrospective case
      series. SETTING: Tertiary care referral centre. PATIENTS: Forty-one patients who
      underwent acetabular revision with a cementless cup were followed up for a mean
      of 3.4 years. INTERVENTIONS: Acetabular revision with a beaded cementless cup in
      all patients. A morcellized allograft was used in 10 patients. OUTCOME MEASURES:
      A modified Harris hip score (range of motion measurement omitted), the SF-36
      health survey, and the Western Ontario McMaster (WOMAC) osteoarthritis index.
      Multivariate analysis was used to evaluate the effects of age, gender,
      morcellized allografting, time to revision from the previous operation,
      acetabular screw fixation and concurrent femoral revision on outcome. RESULTS:
      Gender accounted for a significant portion of the variation seen in the SF-36
      physical component scores (r = 0.36, p = 0.02), with women tending to have worse
      results. Increasing age was associated with lower WOMAC index function scores (r
      = 0.36, p = 0.03), whereas concurrent femoral revision tended to have a positive
      effect on WOMAC index function (r = 0.39, p = 0.01). None of the potential
      clinical predictors had any significant effect on the SF-36 mental component
      scores, or WOMAC index pain and stiffness scores. CONCLUSIONS: In cementless
      acetabular revision arthroplasty, physical function, as measured by generic and
      limb-specific scales, may be affected by gender, age and the presence of a
      concurrent femoral revision. Time to revision from the previous operation,
      morcellized allografting and screw fixation of the acetabulum did not affect
      outcomes. This information may provide some prognostic value for patients'
      expectations.

PMID- 10948688
TI  - Functional outcome after acetabular revision with roof reinforcement rings.
AB  - OBJECTIVE: To evaluate the role for potential predictors of functional outcome
      after acetabular arthroplasty and to assess the results of revision with the use
      of a roof reinforcement ring. DESIGN: A retrospective case series. SETTING: A
      tertiary-care referral centre. PATIENTS: Twenty-four patients (average age 72.7
      years) who had undergone acetabular revision with a roof reinforcement ring were
      followed up for an average of 2.8 years. INTERVENTIONS: Revision acetabular
      arthroplasty was performed using either the Mueller or Burch Schneider roof
      reinforcement ring, bone grafting and a cemented polyethylene cup. OUTCOME
      MEASURES: A modified Harris hip score (range of motion omitted), the SF-36 health
      survey and the Western Ontario McMaster (WOMAC) osteoarthritis index measured
      outcome. Multivariate analysis was used to determine the effects of certain
      clinical factors (age, sex, time to revision from previous hip operation and
      number of previous revisions) on outcome. RESULTS: Patients reported disability
      both on hip-specific and general health measures. The time to revision from
      previous operation positively correlated with SF-36 mental component scores (p =
      0.003), WOMAC function (p = 0.04) and WOMAC pain (p = 0.03). Age, gender and
      number of past revisions did not affect outcome. CONCLUSIONS: Patients who
      undergo acetabular revision with a roof ring will continue to have some
      disability in the first 3 years after the procedure. A greater time between the
      previous operation and the revision operation is associated with a better
      outcome. Patients' expectations of postoperative results should be realistic in
      the face of a challenging reconstructive procedure.

PMID- 10948689
TI  - Management of adult splenic injuries in Ontario: a population-based study.
AB  - OBJECTIVES: To determine the population-based incidence of splenic injuries in
      the Province of Ontario, the proportion of splenic injuries treated by
      observation, splenectomy and splenorrhaphy, changes in management over time and
      the variation in management of splenic injuries among Ontario hospitals. DESIGN:
      A retrospective cohort study. PATIENTS: All adults (older than 16 years) admitted
      with a diagnosis of splenic injury (clinical modification of the International
      Classification of Diseases, 9th revision) to acute care hospitals in Ontario
      between 1991 and 1994, identified from the Ontario Trauma Registry. RESULTS: The
      incidence of splenic injury was 1.7 cases per 1000 trauma admissions per year.
      Patients with splenic injury were young (median age 32 years) and male (71%), and
      the death rate was 8%. Observation was the commonest method of treatment (69%),
      followed by splenectomy (28%) and splenorrhaphy (4%). The use of observation
      increased over the study period from 59% to 75% (p < 0.001). There was
      significant variation in the use of observation among hospitals (range 11% to
      100%, p < 0.0001). CONCLUSIONS: The majority of splenic injuries are managed by
      observation with an acceptable hospital death rate. The use of observation has
      increased over time, confirming the growing adoption of this management approach
      by most hospitals in the province when feasible. Splenorrhaphy was infrequently
      performed despite reports to the contrary from many centres in the United States.
      There was significant variation in splenic injury management, suggesting the need
      for further refinement and dissemination of practical guidelines for splenic
      salvage.

PMID- 10948690
TI  - The safe use of epidural anesthesia after subcutaneous injection of low-dose
      heparin in general abdominal surgery.
AB  - OBJECTIVE: To determine if epidural anesthesia after the subcutaneous injection
      of low-dose unfractionated heparin (LDUH) in patients who undergo elective bowel
      surgery is safe with respect to hemorrhagic complications. DESIGN: A prospective
      cohort study. SETTING: Two hospitals affiliated with the Universite de Montreal.
      PATIENTS: Fifty patients scheduled for elective bowel surgery. INTERVENTION:
      Subcutaneous injection of 5000 units of LDUH and elective surgery for colonic
      carcinoma, chronic diverticulosis or inflammatory bowel disease. MAIN OUTCOME
      MEASURES: Activated partial thromboplastin time (APTT), anti-IIa and anti-Xa
      heparin levels measured before and 2 and 4 hours after injection of LDUH.
      RESULTS: In no case was the heparin anti-IIa or anti-Xa level higher than 0.20
      U/mL, which is considered a significant detectable level of heparin. CONCLUSION:
      LDUH given subcutaneously is not associated with significant detectable heparin
      levels, so epidural anesthesia should be safe when performed 2 hours after LDUH
      injection in patients who undergo general abdominal surgery in the absence of any
      other impairment of hemostasis.

PMID- 10948691
TI  - A needs assessment of surgical residents as teachers.
AB  - OBJECTIVE: To determine the needs of surgical residents as teachers of clinical
      clerks. DESIGN: A needs assessment survey. SETTING: Department of Surgery,
      University of Toronto. PARTICIPANTS: Clinical clerks and surgical residents and
      staff surgeons. METHODS: Three stakeholder groups were defined: staff surgeons,
      surgical residents and clinical clerks. Focus-group sessions using the nominal
      group technique identified key issues from the perspectives of clerks and
      residents. Resulting information was used to develop needs assessment surveys,
      which were administered to 170 clinical clerks and 190 surgical residents.
      Faculty viewpoints were assessed with semi-structured interviews. Triangulation
      of these 3 data sources provided a balanced approach to identifying the needs of
      surgical residents as teachers. RESULTS: Response rates were 64% for clinical
      clerks and 66% for surgical residents. Five staff surgeons were interviewed.
      Consensus was noted among the stakeholder groups regarding the importance of
      staff surgeon role modelling and feedback, resident attitude, time management,
      knowledge of clerks' formal learning objectives, and appropriate times and
      locations for teaching. Discrepancies included a significant difference in
      opinion regarding the residents' capacity to address clerks' individual learning
      needs and to foster good team relationships. Residents indicated that they did
      not receive regular feedback regarding their teaching and that staff did not
      place an emphasis on their teaching role. CONCLUSIONS: This study has, from a
      multi-source perspective, assessed the needs of surgical residents as teachers.
      These needs include enhancing residents' education regarding how and what to
      teach medical students on a surgical rotation, and a need for staff surgeons to
      increase feedback to residents regarding their teaching.

PMID- 10948692
TI  - Visceral artery aneurysm.

PMID- 10948693
TI  - Needlescopic decapsulation of a splenic epithelial cyst.
AB  - As technology advances, the techniques of laparoscopic surgery are being refined
      and their application is expanding to include many disease processes and organs.
      The new-generation laparoscopic instruments are becoming smaller (less than 5
      mm). Expected advantages include improvements in cosmesis and patient
      satisfaction, and decreased postoperative analgesic requirements. Non-neoplastic
      cysts of the spleen are rare, and their management has evolved from total open
      splenectomy to laparoscopic cyst decapsulation. A 22-year-old woman with a
      symptomatic 10-cm epithelial cyst was treated by splenic decapsulation with
      needlescopic instruments (3 mm or smaller). Three trocars were used: one 12-mm
      umbilical and two 3-mm subcostal ports. The cyst was punctured by a Veress
      needle, and after drainage of straw-coloured fluid, circumferential decapsulation
      with 5-mm laparoscopic shears through the umbilical port site was done. The
      patient was discharged within 24 hours, having had a single intramuscular
      injection of meperidine and an excellent cosmetic result.

PMID- 10948694
TI  - Basic pharmacodynamic models for agents that alter production of natural cells.
AB  - Basic indirect pharmacodynamic models for agents which alter the generation of
      natural cells based on a life-span concept are introduced. It is assumed that
      cells (R) are produced at a constant rate (kin), survive for a specific duration
      TR, and then are lost. The rate of cell loss must equal the production rate but
      is delayed by TR. A therapeutic agent can stimulate or inhibit the production
      rate according to the Hill function: 1 +/- H(C(t)) where H(C(t)) contains
      capacity (Smax) and sensitivity (SC50) constants and C(t) is a pharmacokinetic
      function. Thus an operative model is [equation: see text] with the baseline
      condition R0 = kin.TR. One- and two-compartment catenary cell models were
      examined by simulation to describe the role of pharmacokinetics and cell
      properties. The area under the effect curve (AUCE) was derived. The models were
      applied to literature data to describe the stimulatory effects of single doses of
      hematopoietic growth factors such as granulocyte colony-stimulating factor (G
      CSF) on neutrophils, thrombopoietin (TPO) on platelets, and erythropoietin (EPO)
      on reticulocytes in blood. The models described experimental data adequately and
      provided cell life-spans and SC50 values. The proposed cell production/loss
      models can be readily used to analyze the pharmacodynamics of agents which alter
      cell production yielding realistic physiological parameters.

PMID- 10948695
TI  - Assuming peripheral elimination: its impact on the estimation of pharmacokinetic
      parameters of muscle relaxants.
AB  - For anesthetic drugs undergoing nonorgan-based elimination, there is a definite
      trend towards using pharmacokinetic (PK) models in which elimination can occur
      from both central (k10) and peripheral compartments (k20). As the latter cannot
      be assessed directly, assumptions have to be made regarding its value. The
      primary purpose of this paper is to evaluate the impact of assuming various
      degrees of peripheral elimination on the estimation of PK parameters. For doing
      so, an explanatory model is presented where previously published data from our
      laboratory on three muscle relaxants, i.e., atracurium, doxacurium, and
      mivacurium, are used for simulations. The mathematical aspects for this
      explanatory model as well as for two specific applications are detailed. Our
      simulations show that muscle relaxants having a short elimination half-life are
      more affected by the presence of peripheral elimination as their distribution
      phase occupies the major proportion of their total area under the curve. Changes
      in the exit site dependent PK parameters (Vdss) are also mostly significant when
      k20 is smaller than k10. Although the physiological processes that determine drug
      distribution and those affecting peripheral elimination are independent, the two
      are mathematically tied together in the two-compartment model with both central
      and peripheral elimination. It follows that, as greater importance is given to
      k20, the rate of transfer from the central compartment (k12) increases. However,
      as a result of a proportional increase in the volume of the peripheral
      compartment, peripheral concentrations remain unchanged whether or not peripheral
      elimination is assumed. These findings point out the limitations of compartmental
      analysis when peripheral elimination cannot be measured directly.

PMID- 10948696
TI  - Indirect-response modeling of desmopressin at different levels of hydration.
AB  - The objective of the present study was to investigate the pharmacokinetics (PK)
      and pharmacodynamics (PD) of desmopressin in healthy male subjects at different
      levels of overhydration. Also, we examined if an indirect-response model could be
      related to renal physiology and the pharmacological action of desmopressin. Eight
      healthy male subjects participated in this open, randomized crossover study with
      three periods. Each subject was orally water loaded (0 to 20 ml.kg-1 body weight)
      on 3 study days in order to achieve three different levels of hydration. After
      the initial water load, urine was voided every 15 min and the volumes were
      measured. To ensure continuous overhydration the subjects replaced their fluid
      loss with drinking-water. When a steady-state diuresis was achieved after
      approximately 2 hr, 0.396 microgram of desmopressin was administered
      intravenously as a bolus injection. Blood was sampled and urine was collected at
      intervals throughout the study day (10 hr). An indirect-response model, where
      desmopressin was assumed to inhibit the elimination of response, was fit to the
      urine osmolarity data. There were no statistically significant effects of
      different levels of hydration, as expressed by urine flow rate at baseline, on
      the estimates of the PK and PD model parameters. The calculated terminal half
      lives of elimination (t1/2 beta) ranged between 2.76 and 8.37 hr with an overall
      mean of 4.36 hr. The overall means of plasma clearance and the volumes of
      distribution of the central compartment (Vc) and at steady state (Vss) were
      estimated to be 1.34 (SD 0.35) ml.min-1.kg-1, 151 (SD28) ml.kg-1, and 386 (SD 63)
      ml.kg-1, respectively. High urine flow rate, indicating overhydration, produced a
      diluted urine and thus a low osmolarity at baseline (R0). The effect of the urine
      flow rate on the urine osmolarity at baseline was highly significant (p <
      0.0001). The mean values for IC50 and the sigmodicity factor (gamma) were 3.7 (SD
      1.2) pg ml-1 and 13.0 (SD 3.5), respectively. In most cases when there was a high
      urine flow rate at baseline, the model and the estimated PD parameters could be
      related to the pharmacological action of desmopressin and renal physiology. Thus,
      the indirect-response model used in this study offers a mechanistic approach of
      modeling the effect of desmopressin in overhydrated subjects.

PMID- 10948697
TI  - Drug-drug pharmacodynamic interaction detection by a nonparametric population
      approach. Influence of design and of interindividual variability.
AB  - Population approaches are appealing methods for detecting then assessing drug
      drug interactions mainly because they can cope with sparse data and quantify the
      interindividual pharmacokinetic (PK) and pharmacodynamic (PD) variability.
      Unfortunately these methods sometime fail to detect interactions expected on
      biochemical and/or pharmacological basis and the reasons of these false negatives
      are somewhat unclear. The aim of this paper is firstly to propose a strategy to
      detect and assess PD drug-drug interactions when performing the analysis with a
      nonparametric population approach, then to evaluate the influence of some design
      variates (i.e., number of subjects, individual measurements) and of the PD
      interindividual variability level on the performances of the suggested strategy.
      Two interacting drugs A and B are considered, the drug B being supposed to
      exhibit by itself a pharmacological action of no interest in this work but
      increasing the A effect. Concentrations of A and B after concomitant
      administration are simulated as well as the effect under various combinations of
      design variates and PD variability levels in the context of a controlled trial.
      Replications of simulated data are then analyzed by the NPML method, the
      concentration of the drug B being included as a covariate. In a first step, no
      model relating the latter to each PD parameter is specified and the NPML results
      are then proceeded graphically, and also by examining the expected reductions of
      variance and entropy of the estimated PD parameter distribution provided by the
      covariate. In a further step, a simple second stage model suggested by the
      graphic approach is introduced, the fixed effect and its associated variance are
      estimated and a statistical test is then performed to compare this fixed effect
      to a given value. The performances of our strategy are also compared to those of
      a non-population-based approach method commonly used for detecting interactions.
      Our results illustrate the relevance of our strategy in a case where the
      concentration of one of the two drugs can be included as a covariate and show
      that an existing interaction can be detected more often than with a usual
      approach. The prominent role of the interindividual PD variability level and of
      the two controlled factors is also shown.

PMID- 10948698
TI  - [The prevention of bone mineral loss with hormonal replacement therapy in
      premenopausal women on dialysis with estrogen deficiency].
AB  - In 25-30% of premenopausal dialysis women low serum estrogen concentrations are
      observed. This "premature menopause" can significantly contribute to accelerated
      bone loss. The aim of the study was to evaluate the effect of estrogen-gestagen
      replacement therapy on bone mineral density (BMD) in hemodialysis women with
      secondary to uremia estrogen deficiency. Among 20 hemodialysis women, aged 18-45
      years, with serum 17 beta-estradiol < 30 pg/ml, ten (group I) received
      transdermal estradiol with cyclic addition of noretisterone acetate (Estracomb
      TTS 50/0.25), and another ten formed the control group (group II). BMD was
      evaluated by dual photon x-ray absorptiometry (DEXA, Lunar) in: lumbar spine (L2
      L4), 1/3 distal radius and femoral neck, before and after the study. Serum 17
      beta-estradiol concentrations were measured before, and after 1, 3, 6 and 12
      months of the study. After one year, in group I, in which serum 17 beta-estradiol
      normalized already during the first month (p < 0.001), an increase of in BMD was
      noted, although significant only in L2-L4 (p < 0.05). In group II, no change in
      serum 17 beta-estradiol and mild but insignificant decrease in BMD were observed.
      However, a comparison of BMD values after 12 months in both groups revealed the
      marked differences in all studied sites (p < 0.01, p < 0.02, p < 0.05 in L4-L2,
      distal radius and femoral neck, respectively). The mean serum calcium, phosphate,
      PTH and alkaline phosphatase activity were similar in both groups and did not
      change during the study. In premenopausal hemodialysis women with estrogen
      deficiency, hormonal replacement therapy inhibits bone demineralization and can
      be useful in prevention of early osteoporosis.

PMID- 10948699
TI  - [Hormonal replacement therapy and lipid metabolism in women on hemodialysis with
      secondary to uremia estrogen deficiency].
AB  - It has been reported that postmenopausal women taking hormonal replacement
      therapy (HRT) are at reduced risk for cardiovascular disease mainly because of
      favorable changes in serum LDL- and HDL-cholesterol. However, the therapy is also
      known to increase hepatic triglyceride production. Cardiovascular events are the
      leading cause of death in patients on dialysis and lipid abnormalities are
      common. The aim of the study was to evaluate the influence of HRT on lipid
      metabolism in premenopausal women undergoing hemodialysis with premature
      oestrogen withdrawal. 25 hemodialyzed women, aged 37 +/- 9 years (19-44 years)
      with serum 17 beta-estradiol < 30 pg/ml were divided into: group I (n = 13)
      treated with transdermal HRT (estradiol with cyclic norethisterone acetate-
      Estracomb TTS 50/0.25; Novartis), and control group II (n = 12). Before the
      treatment serum LDL-cholesterol concentrations were increased in 24% and serum
      triglycerides in 40% of patients, whereas HDL-cholesterol was decreased in 72% of
      patients. During one year, in group I a noticeable, 15% increase in serum HDL
      cholesterol was observed from 0.90 +/- 0.23 to 1.04 +/- 0.19 mmol/l (34.8 +/- 8.8
      to 39.8 +/- 7.4 mg/100 ml; p < 0.01). It was parallel to the increase in serum 17
      beta-estradiol concentrations (from 20.5 +/- 8.91 to 50.3 +/- 17.20 pg/ml; p <
      0.01). Serum LDL-cholesterol and triglycerides did not change significantly. In
      the control group all those values remained unchanged. CONCLUSIONS: In
      hemodialysis women with premature estrogen deficiency the transdermal cyclic HRT
      leads to the clinically important increase in serum HDL-cholesterol without
      significant changes in serum triglyceride concentrations and could be beneficial
      in reducing cardiovascular risk in this population.

PMID- 10948700
TI  - [The selected pro- and anti-inflammatory cytokines in the patients with coronary
      heart disease: preliminary communication].
AB  - Recent findings suggest that inflammation and cytokines regulation may play a
      role in the pathogenesis of atherosclerosis and coronary heart disease. The aim
      of this study was to assess serum concentrations of selected pro- (TNF alpha) and
      antiinflammatory (IL-10) cytokines in patients with coronary heart disease. We
      studied 29 patients with coronary heart disease: 14 with stable angina (group I)
      and 15 with unstable angina (group II). The control group (group K) consisted of
      10 healthy subjects. Patients with inflammatory diseases, previous myocardial
      infarction (last 6 months) and with ECG abnormalities, that would invalidate ST
      segment analysis, were excluded from examined groups. We evaluated: clinical
      state of patients and results of some diagnostic examinations (lipids, ECG,
      echocardiography, coronary angiography, concomitant diseases). In each patients
      serum levels of TNF alpha and IL-10 were measured according to the special
      protocol by ELISA. The mean serum concentrations of TNF alpha and IL-10 were
      significantly higher in group I (respectively: 18.75 +/- 11.7 pg/ml, 89.0 +/-
      114.9 pg/ml) and II (14.21 +/- 5.9 pg/ml, 49.38 +/- 72.9 pg/ml) in comparison to
      the healthy subjects (9.41 +/- 1.7 pg/ml, 9.69 +/- 4.5 pg/ml). We found positive
      correlations between mean TNF alpha and IL-10 concentrations in group II (48
      hours after last symptom) and between mean TNF alpha concentration and LVM (left
      ventricular mass), LVMI (left ventricular mass index) in group I. The
      concentrations of TNF alpha and IL-10 did not correlate with other clinical
      parameters. The results of our study suggest that serum concentrations of pro-
      (TNF alpha) and antiinflammatory (IL-10) cytokines may be increased in patients
      with stable and unstable angina. These increased concentrations do not reflect
      the clinical state of patients.

PMID- 10948701
TI  - [Angiotensin converting enzyme gene polymorphism in type 2 diabetes mellitus].
AB  - The aim of this study is the assessment of the association of human angiotensin
      converting enzyme gene I/D polymorphism with type 2 diabetes in 155 diabetic
      patients and 139 healthy individuals. These polymorphism were studied using
      polymerase chain reaction. Angiotensin converting enzyme gene DD genotype
      associated with type 2 diabetes in overweight and obese patients and patients
      with normal total plasma cholesterol. There is also association of DD genotype
      with arterial hypertension and with myocardial infarction in type 2 diabetic
      patients.

PMID- 10948702
TI  - [Drivers with obstructive sleep apnea as potential authors of car accidents].
AB  - The aim of this work was to estimate excessive somnolence and frequency of
      episodes of dozing off during driving a car in patients with obstructive sleep
      apnea. Result of questionnaire and polysomnographic investigations were analysed
      in a group of 503 patients. Mean age for the whole group was 49.2 +/- 9.7 of
      years, BMI 32.1 +/- 1.4 kg/m2 and the value for apnea and hypopnea index 45.4 +/-
      24.8. Excessive somnolence during driving was reported by 49.1% of patients.
      31.2% of the group notified at least one episode of falling asleep while driving
      a car. Sleepy drivers (group A) were significantly younger (46.5 +/- 9.2 vs 50 +/
      9.8 years) and had higher values of BMI (34.1 +/- 7 vs 31.1 +/- 5.5 kg/m2) than
      the others (group B) Results of polysomnographic investigation showed more severe
      sleep apnea in the group A. Mean value of AHI for this group was 52.5 +/- 26.1 vs
      41.6 +/- 23.5 in the group B. Besides, somnolence in many other practical
      situations was more often considered as a serious problem in the group A.

PMID- 10948703
TI  - [Neurological disturbances in the course of glucagonoma: a case report].
AB  - A case of 40-year-old patient with glucagonoma associated with neurological and
      consciousness disturbances is reported. The diagnosis of the tumour was based on
      clinical manifestations (diabetes mellitus, anaemia, weight loss, distant
      metastases), visualisation (USG, CT of the abdomen) and immunohistochemical
      staining of the biopsy of tumour metastatis to the liver. During the progress of
      disease paraplegia, other neurological symptoms and three episodes of coma were
      observed. This should be associated with the neurologic paraneoplastic syndrome
      and hepatic failure due to diffuse metastases to the liver, especially when no
      metastases to the central nervous system were found in CT. Although patient was
      treated with chemotherapy, disseminated neoplasmatic process was the cause of the
      fatal outcome.

PMID- 10948704
TI  - [Pancreatic preparations in clinical practice].

PMID- 10948705
TI  - [Diet and gastrointestinal cancers].

PMID- 10948706
TI  - [Cyclooxygenase-2 inhibitors and cancer prevention].

PMID- 10948707
TI  - [Left ventricle hypertrophy as a sudden death risk factor in patients with
      chronic kidney failure treated with hemodialysis].

PMID- 10948708
TI  - [C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in
      patients with myocardial infarction].
AB  - Hyperhomocysteinemia is thought to be an independent risk factor for coronary
      heart disease. Increased plasma homocysteine level can result from malnutrition
      (e.g. folate deficiency) and/or genetic-related disturbances.
      Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the synthesis of 5
      methyltetrahydrofolate, the methyl donor for homocysteine remethylation to
      methionine. Transition of cytosine (C) to thymidine (T) at nucleotide position
      677 of MTHFR gene causes alanine 226-to-valine substitution, and in consequence
      results in decreased enzyme activity and increased homocysteine level. Therefore,
      the aim of our study was to estimate the frequency distribution of C677T MTHFR
      polymorphism in patients with past myocardial infarction (MI), and to evaluate
      the association between this polymorphism and age of MI onset or left ventricular
      mass (LVM). The study was performed in 100 MI patients aged from 34 to 76 years
      and in control group consisted of 100 age- and gender-matched non-MI subjects.
      Applying PCR followed by Hinf I digestion of amplification products no
      significant difference in the frequency distribution of C677T MTHFR genotypes has
      been found between both groups (MI patients: 46% CC, 45% CT and 9% TT, and
      control group: 39% CC, 50% CT and 11% TT, respectively). No significant
      association between MTHFR genotypes and age of MI onset or LVM has been found in
      MI group. The results of our study suggest that C677T polymorphism of MTHFR gene
      is not a risk factor for myocardial infarction in Polish population.

PMID- 10948709
TI  - [Left ventricular diastolic function evaluated by Doppler echocardiography in
      coronary artery disease in relation to to systolic function].
AB  - The aim of the study was to assess the relationship between left ventricular (LV)
      diastolic dysfunction measured by Doppler mitral flow indices (D.m.f.i.) and LV
      systolic performance in coronary artery disease (CAD). 107 pts with confirmed CAD
      without or after MI in I, II NYHA class was divided into 2 groups according to
      ejection fraction (EF) value = 55%. 13 D.m.f.i. regarding to the time, velocity,
      flow volume and derivates were calculated. In the patient with CAD with normal
      EF, the diastolic dysfunction was characterised by the impaired relaxation. There
      were prolonged isovolumic relaxation time IVRT and deceleration time of early
      filling flow DT, reduced early filling fraction EFF and increased the atrial
      filling fraction AFF, decreased E/A ratio and E/A-VTI. The regression analysis
      revealed the positive correlation between EF and DT r = 0.35 and inverse
      correlation between wall motion score index WMSI and DT r = DT r = -0.33. The
      stepwise regression analysis revealed that EF and WMSI are independent factors
      influencing on DT. Our results confirm that diastolic dysfunction precedes the
      systolic dysfunction in CAD. The correlation between D.m.f.i. and LV systolic
      function parameters were obtained. The results suggest that the LV systolic
      function should be take to account in the Doppler mitral flow analysis.

PMID- 10948710
TI  - [Low molecular weight heparin (LMWH) modulates migration of peripheral blood
      mononuclear cells and neutrophils of asthmatics].
AB  - Evidence has now accumulated that heparin can significantly affect immune
      response including allergic inflammation. Cell migration is supposed to be very
      crucial in this process. Thus the aim of that study was to investigate whether
      low molecular weight heparin-nadroparine is chemoattractant for some inflammatory
      cells in asthmatics. Peripheral blood mononuclear cells (PBMC) and neutrophils
      from 15 asthmatics were obtained by gradient centrifugation. Chemotaxis was
      compared with that induced with known chemoattractants-fMLP and IL-8. We found
      that nadroparine caused significant and dose dependent chemotaxis of PBMC and
      comparable with influence of fMLP and IL-8. Nadroparine amplified chemotaxis of
      neutrophils but not significantly. Chemotaxis induced by fMLP and IL-8 was
      diminished when blood cells were incubated earlier with 50 mg of nadroparine.

PMID- 10948711
TI  - [Insulin-receptor gene polymorphism in type 2 diabetic patients].
AB  - The aim of this study was the assessment of the association of human insulin
      receptor gene NsiI polymorphism with type 2 diabetes in 125 diabetic patients and
      110 healthy individuals. These polymorphism were studied using polymerase chain
      reaction. It was found the association between N2N2 genotype and type 2 diabetes
      in patients with normal body weight and with positive family history. The
      association of the susceptibility to myocardial infarction with N2N2 genotype was
      also observed.

PMID- 10948712
TI  - [Myocardial scintigraphy with technetium 99m MIBI in patients with left bundle
      branch block].
AB  - Myocardial perfusion scintigraphy is a non-invasive method helpful for evaluating
      the coronary heart disease. Its use may be particularly indicated in cases of
      inconclusive ECG (i.e. in left bundle branch block, LBBB). On the other hand
      there are observations indicating the decreased accumulation of the radiotracer
      in the septal segments of myocardium in patients with left bundle branch block
      (LBBB). This phenomenon previously described for the thallium-201, recently was
      also reported in the MIBI 99mTc studies. Purpose of the present study were: (1)
      to check the frequency of the diminished uptake of the radiotracer (MIBI 99mTc)
      in the LBBB patients, and (2) to test its interference with the evaluation of the
      coronary heart disease. MATERIALS AND METHODS: Our observation material included
      42 patients in mean age 49 +/- 7 yr (26 women) divided into 3 groups: Group I--12
      patients without intraventricular conduction disorders and with normal
      coronarography (the reference group), Group II--15 patients with LBBB and no
      signs of coronary artery disease in angiography and Group III--15 patients with
      LBBB and coronary artery disease confirmed by angiography. All patients underwent
      stress-rest perfusion scintigraphy according to a 2-days protocol. Submaximal
      bicycle exercise test was performed using the Bruce protocol. A single-head SPECT
      scintillation camera (DIACAM-Siemens) was used to acquire 64 views over 180
      degrees. Acquisition was started 60-90 minutes after injection of MIBI 99mTc (800
      MBq). After generating tomographic images their reorientation towards the left
      ventricle axes and creating the bull's eye polar maps were carried out with the
      aid of manufacturer's programs. RESULTS: The mean decrease of the radiotracer
      accumulation in the septal segment was similar in both groups of patients with
      LBBB (32.7 +/- 9.5 vs 28.5 +/- 8.6 in stress and 27.6 +/- 9.5 vs 27.5 +/- 7.9 in
      rest in groups II and III, respectively). It was, however, significantly less
      pronounced in the reference (I) group (the mean decrease being 17.7 +/- 4.7 or
      16.9 +/- 5.5 in stress and rest studies, respectively). Distribution of MIBI
      99mTc in the myocardium was more homogeneous in the reference group (the maximal
      differences of the radiotracer accumulation never exceeded 45%) than in the LBBB
      groups. In the group II defects of the maximal depth over 46% were observed in 9
      patients (60%), and in the group C in 12 patients (80%). In 6 patients of the
      latter group maximal depth of decets exceeded 56% (value never found in group
      II). CONCLUSION: The diminished uptake of MIBI 99mTc in the septal segment of the
      left ventricle is a common phenomenon. In some cases it may interfere with the
      evaluation of the perfusion scintigraphic studies. The more pronounced defects,
      however, may be significant for the coronary artery disease.

PMID- 10948713
TI  - [The efficacy of the substitution of carnivit in patients with chronic failure
      treated with hemodialysis].
AB  - Low serum concentration of the carnitine is one of the causes of muscle weakness
      and cardiomyopathy in patients with chronic renal failure treated by
      hemodialysis. The carnitine facilitate transport of the free fatty acid into the
      straitened muscle cells where the product of oxidation is energy-ATP. In the
      present paper we presented the investigation of the influence of L-carnitine
      substitution on cardiac performance. The results indicate the positive influence
      of this treatment on metabolic and haemodynamic cardiac parameters. The
      subjective patients opinion of L-carnitine treatment was also positive.

PMID- 10948714
TI  - [Factors causing renal failure in patients with disseminated lupus erythematosus:
      description of three cases].
AB  - We describe three cases of patients with systemic lupus erythematosus in which
      additional infections: mycotic, bacterial and viral deteriorated renal function
      and patients needed the dialysis treatment. The patients with autoimmunologic
      disorders are very sensitive for different infections which need rapid diagnosis
      and intensive treatment.

PMID- 10948715
TI  - [Diagnosis of bronchial asthma].

PMID- 10948716
TI  - [Pathological mechanisms of coronary in-stent restenosis].

PMID- 10948717
TI  - [Left ventricle function in patients with chronic renal failure treated with
      hemodialysis].

PMID- 10948718
TI  - [Cardiological problems in patients with neoplastic disease].

PMID- 10948719
TI  - [Fifth Congress of Internal Medicine of Yugoslavia, Belgrade, October 17-21,
      1999].

PMID- 10948720
TI  - [Conference: opioids in the treatment of chronic pain: moving into the future
      with Durogestic, Valencia, November 19-20, 1999].

PMID- 10948722
TI  - Methodologic concerns regarding estimates of physical violence in sexual
      coercion: overstatement or understatement?
AB  - Self-report measures of sexual violence that ask women whether they have
      experienced threats of physical violence have attracted criticism in recent
      years; detractors claim that these measures lead researchers to overestimate the
      prevalence of sexual violence. Our study explored this issue by collecting data
      on the prevalence of threats versus force in the context of sexual aggression.
      Female undergraduates at two universities (n1 = 69; n2 = 111) were asked about
      their experiences with sexual coercion using a revised version of the Sexual
      Experiences Scale (Koss and Gidycz, 1985). Four of the original items were
      modified to distinguish between sexual contact that occurred as a result of a
      perpetrator using physical force and sexual contact that occurred because a
      perpetrator threatened physical violence. Analyses of the revised items revealed
      that the use of physical force was at least as likely as threats and that for
      some types of sexual acts, physical force was actually more likely than verbal
      threats. Furthermore, prevalence figures for three of the four types of sexual
      acts considered were not significantly altered by collapsing threat of force with
      use of force. Implications for future research on women's experiences of sexual
      coercion are discussed.

PMID- 10948721
TI  - Self-administered questionnaires versus face-to-face interviews in assessing
      sexual behavior in young women.
AB  - Effects of mode of assessment, person, and situational variables on the accuracy
      of self-reports of sexual behavior remain uncertain. To evaluate these
      influences, 190 young women completed measures of erotophilia and social
      desirability and then monitored their health-related behaviors with a diary for 8
      weeks. They returned on two occasions to complete either a face-to-face interview
      (FTFI) or a self-administered questionnaire (SAQ) regarding their behavior over
      the same interval. To check the apparent accuracy of participants' retrospective
      self-reports, a difference score was calculated by subtracting responses obtained
      on the FTFI or SAQ from the diary card. Results indicated that both modes of
      assessment were reliable; reliability did not differ as a function of mode of
      assessment. However, SAQs elicited less discrepant responses for protected
      vaginal sex; SAQ and FTFI reports for unprotected sexual behaviors were
      equivalent. Situational and person variables did not predict accuracy scores,
      which were impaired at higher frequencies of behavior. Results suggest that both
      modes of assessment were reliable and SAQs may be more accurate for some sexual
      behaviors.

PMID- 10948723
TI  - Nurse-patient sexual contact in psychiatric hospitals.
AB  - Sexual contacts between nurses and patients in psychiatric hospitals have not
      been investigated systematically. The aim of the present study was to determine
      the frequency of nurse-patient sexual relationships and their prominent
      characteristics on the one hand and the nurses' attitudes towards these contacts
      on the other. A questionnaire was mailed to 714 nurses employed at two
      psychiatric hospitals. Although 94% of the 279 respondents considered sexual
      contact (defined as "physical contact between a patient and a nurse, in which
      sexual arousal occurred in the nurse") to be inappropriate, 17% of the male and
      11% of the female responding nurses reported having had such contacts with
      patients.

PMID- 10948724
TI  - Birth order in a contemporary sample of gay men.
AB  - The birth order of a contemporary North American sample of 97 gay men was
      quantified using Slater's Index. For the 84 probands with at least one sibling,
      the results showed a late mean birth order compared with the expected value of
      .50. Additional birth order indices derived from Slater's Index suggested that
      the mean later birth order was accounted for more strongly by the proband's
      number of older brothers than by his number of older sisters. The present
      findings constitute a replication of a series of recent studies and add to the
      growing body of evidence that birth order is a reliable correlate of sexual
      orientation in males.

PMID- 10948725
TI  - Heterosexual anal intercourse: an understudied, high-risk sexual behavior.
AB  - Differences between heterosexuals who have or have not engaged in anal
      intercourse were analyzed. Though anal intercourse is widely recognized as an
      activity that greatly increases the risks for HIV transmission, it has received
      little attention in heterosexual populations. A questionnaire was mailed to a
      random sample of university students, a population in which many people engage in
      vaginal intercourse with several partners each year. The three largest minorities
      were randomly oversampled in order that all four major ethnic/racial groups could
      be statistically evaluated for possible differences. Almost 23% of nonvirgin
      students had engaged in anal intercourse. Regression analysis indicated that
      people who had participated in anal intercourse were more likely than people
      without anal experience to have been younger at first vaginal intercourse, to be
      older when the data were collected, to have engaged in vaginal intercourse in the
      last three months before data collection, to be more erotophilic, to use less
      effective contraceptive methods, and to have used no condom at last coitus.
      Overall, people who engage in anal intercourse take more sexual risks when
      engaging in vaginal intercourse than do people without anal experience. No major
      ethnic/racial differences were detected. Sexologists have not explored anal sex
      in much detail, hence we have been weak in educating those 20 to 25% of young
      adults who are not reluctant or (inhibited about) exploring anal intercourse. As
      young adults use condoms less for anal than vaginal intercourse, they have not
      learned enough about the risk of anal sex.

PMID- 10948726
TI  - Attitudes toward transsexualism in a Swedish national survey.
AB  - A general inventory of the views on sex reassignment and attitudes toward
      transsexuals in Sweden was attempted. Whether the view on these matters differ
      between people embracing biological theories in explanation of transsexualism and
      those embracing psychological theories was tested. Third, whether men and the
      older age groups hold a different view on transsexualism than women and younger
      age groups was investigated. For these purposes, in October-December 1998, a
      questionnaire was mailed to a randomly selected national sample of 992 Swedish
      residents; 668 persons returned the questionnaire, giving a 67% response rate.
      Results showed that a majority supports the possibility for transsexuals to
      undergo sex reassignment; however, 63% thought that the individual should bear
      the expenses for it. In addition, a majority supported transsexuals' right to get
      married in their new sex and their right to work with children. Transsexuals'
      right to adopt and raise children was supported by 43%, whereas 41% were opposed.
      Results indicated that those who believed that transsexualism is caused by
      biological factors had a less restrictive view on transsexualism than people who
      held a psychological view. Men and the older age group were found to hold a more
      restrictive view on these issues than women and the younger age group. Future
      studies should address these questions to elucidate differences between cultures
      and the process of change in attitudes over time.

PMID- 10948727
TI  - The field of sex research: responsibility to ourselves and to society.

PMID- 10948728
TI  - [Surgical clinical studies and their practical realization].
AB  - The employment of the optimal therapeutic option according to the best current
      knowledge is called evidence-based medicine (EBM). Moreover, considering the cost
      explosion in public health systems, EBM should contribute towards economical and
      targeted use of the restricted resources and towards quality assurance in
      medicine. Obviously, this is applicable to the operative specialties and can be
      termed as evidence-based surgery. Surgeons have to do their "homework" about this
      subject and to perform randomized controlled trials (the gold standard with the
      greatest evidence) on a large scale, in order to come up to this expectation in
      future. Evidence-based therapy is essential for the preservation and especially
      for the further development and evolution of high-quality surgery with, at the
      same time, quality assurance in the new millenium. This article presents the
      definition of EBM and its implication in the operative fields. Fundamental
      principles for the practical conduct of clinical randomized controlled trials are
      defined and the specific problems in surgery are discussed.

PMID- 10948729
TI  - [Topics and focuses of clinical studies in gastroenterological surgery].
AB  - High-quality clinical research offers the opportunity to exert a direct influence
      on medical decision-making. To take stock of the current situation in clinical
      gastroenterological surgery, a questionnaire was sent to 171 surgical departments
      focussing on visceral surgery. Of the 93 that responded, 45.2% conducted a total
      of 91 clinical studies. Only 8.8% of these were described as prospective
      randomized clinical studies; 60% were single-center studies. The studies were
      financed from the department budget in 60 cases, supported by industry in 27
      cases and funded by independent institutions such as German Research Foundation
      or the Federal Ministry for Education and Research in 4 cases. Of the researchers
      performing the studies, 7.7% had been exempted from other duties and 92.8% were
      additionally involved in the clinical routine. The majority of the clinical
      studies in Germany deal with diseases of the esophagus and pancreas or with
      chronic inflammatory bowel diseases. The old and new states of the Federal
      Republic of Germany show no appreciable differences in the development and
      performance of clinical studies.

PMID- 10948730
TI  - [Endocrine surgery and evidence-based medicine].
AB  - INTRODUCTION: The aim of this literature review is to classify current knowledge
      on nine questions of current interest for endocrine surgery and their
      classification with regard to levels of evidenced-based medicine (EBM). METHODS:
      The literature in Medline and EMBase was reviewed. Only retrospective or
      prospective comparative studies with statistical analysis were selected. RESULTS:
      (See Table 8.). CONCLUSION: With respect to the current literature, only routine
      identification of the RLN and the minimally-invasive approach for adrenalectomy
      can be regarded as EBM. To answer the remaining questions prospective studies are
      needed.

PMID- 10948731
TI  - [Status of surgical studies in oncology. I].
AB  - Advances in surgery, anesthesiology and in critical care remarkably elevated
      safety of surgical therapy of cancer. However, prognosis of most cancer types as
      esophageal and gastric carcinoma--as discussed in this part of the survey--did
      not improve, even not after adjuvant therapy. To enhance curative resection rate
      chemotherapy and radiation or a combination of both have been performed
      preoperatively. The weakness of radiotherapy is control of distant metastases,
      chemotherapy failed in local tumor control. Multimodal preoperative strategies
      offered enhanced survival in responders, but overall there was no significant
      survival advantage. Until now neither in esophageal nor in gastric cancer
      randomised studies could demonstrate a substantial overall survival benefit after
      extended lymphadenectomy.

PMID- 10948732
TI  - [Status of surgical studies in oncology. II].
AB  - Recent prospective randomised trials dealt with the optimal extent of surgical
      resection as well as with preoperative therapy modalities in pancreatic, rectal
      and breast cancer. In pancreatic cancer extended lymphadenectomy did not improve
      overall survival. Total mesorectal excision remarkably changed surgery for rectal
      cancer. Rate of local recurrence of rectal cancer could be significantly reduced
      by preoperative irradiation. In advanced rectal cancers curative resection and
      sphincter preservation seems possible due to multimodal preoperative therapy. It
      has been demonstrated that in appropriate cases breast-preserving resection is
      comparable to mastectomy with respect to overall survival. Up to now it is not
      quite clear if sentinel node sampling is equivalent to routine lymphadenectomy.
      Following neoadjuvant chemotherapy breast-preservation rate is significantly
      higher, but survival is not significantly increased.

PMID- 10948733
TI  - [Clinical studies in liver transplantation].
AB  - Clinical liver transplantation became an established therapy of end-stage liver
      disease since the first at least medium-term successful liver transplantation in
      1967. Clinical studies have played a major part in improving peri- and
      postoperative therapy in liver transplantation. In this article clinical studies
      of major impact are presented. Main topics are studies dealing with
      immunosuppressants, improvements in surgical techniques, viral infections and
      tumor diseases. Controlled randomized multicentric studies are rare; most of the
      studies are unicentric. Further studies in the fields of reducing side effects of
      immunosuppression, the introduction of monoclonal antibodies and improvement of
      the therapy of viral hepatitis would be helpful. These studies should be
      controlled, randomized and multicentric.

PMID- 10948734
TI  - [Surgical research in the Netherlands. The Dutch experience with clinical studies
      in surgery].
AB  - A large number of good surgical studies have been published in The Netherlands,
      putting the country at the top of the list in the Western world. It is remarkable
      that the highest productivity was found in small countries and in countries with
      a low population. Most of the large European countries have a low scientific
      output according to the method used in the present study. The Scandinavian
      countries, Holland, and Switzerland have the best scientific index according to
      these results. It could be that the larger countries, such as Germany, Italy,
      France, and Spain, tend more to publish in national journals. Perhaps it is not
      common in some some countries and regions to publish data in English--which
      certainly has a negative effect on the scientific index of such a country. The
      high productivity found among Dutch surgeons could be explained by the fact that
      the 700 surgeons in a small country with a relatively high population are well
      organized: Almost all Dutch surgeons are members of the national surgical
      society. All of them can speak and write English very well. Participation in the
      activities organized by the national society is high. Scientific meetings where
      surgeons and assistants get together for a day or two are held twice a year. In
      addition quality controls are carried out at all teaching and nonteaching
      hospitals. Through this the surgeons in this relatively small country know each
      other quite well, which promotes cooperation when studies are undertaken. The
      Netherlands is just large enough for relevant clinical studies to be conducted
      and it may be that we initiate a relatively large number of such studies. It is a
      democratic country in which surgeons and researchers are offered the freedom and
      opportunity to conduct research and publish their results as they like without
      being hindered by hierarchic structures. Together, these factors create a
      scientific climate in The Netherlands which stimulates the organization of
      multicenter and clinical studies.

PMID- 10948735
TI  - [Intraoperative radiotherapy as multimodal therapy approach in epithelial tumors
      of the gastrointestinal system].
AB  - Surgery alone often fails to achieve local control in advanced gastrointestinal
      tumors. With multimodal therapy approaches, both local tumor control and long
      term survival appear to be improved. Intraoperative radiation therapy (IORT) is
      an attempt to achieve higher doses of irradiation while dose-limiting structures
      are surgically displaced. It has been shown previously that both local tumor
      control and long-term survival are improved in patients undergoing surgery
      combined with IORT for both primary and recurrent rectal carcinoma. In advanced
      gastric carcinoma, IORT has achieved optimistic survival results in a few
      studies. In locally advanced pancreatic cancer, an apparent improvement in local
      control has been noted with IORT, but survival has not been prolonged because of
      a high incidence of both liver and peritoneal metastases. The data concerning
      IORT for esophageal carcinoma are not yet sufficient to allow judgement.

PMID- 10948736
TI  - [Extended liver resection in small children under circulatory arrest and "low
      flow" cardiopulmonary bypass].
AB  - In order to perform resections of tumors at critical sites in the liver in young
      children, liver resections in cardiac arrest and deep hypothermia under
      cardiopulmonary bypass have been developed. We report our experience with liver
      resection under cardiopulmonary bypass in three children with hepatoblastoma. In
      the first child the operation was performed under cardiac arrest and, the other
      two children were operated on under "low flow" conditions. The periods under
      cardiopulmonary bypass circulation were well tolerated. Extended right liver
      resections with vascular reconstructions were performed. The postoperative
      increase of liver enzymes was moderate. The increase in GOT was between 100 and
      200 U/l. In spite of the extended tumor growth, reasonable long-term results were
      achieved by resection in combination with chemotherapy. One child has been living
      8 years and another 10 months without tumor recurrence. The third child died due
      to sepsis during adjuvant chemotherapy, after she had recovered well from liver
      resection.

PMID- 10948737
TI  - [Cystic gastric stromal tumors: a diagnostic dilemma?].
AB  - Gastric cysts are a rare disease and their diagnostic work-up often produces
      inconclusive results. We report on four gastric stromal tumors, in part huge,
      with cystic degeneration where the diagnosis and organ of origin remained unclear
      until operation. Considering these tumors as examples we discuss means and limits
      of differential diagnosis, taking into account further diseases with cystic
      formations in the gastric wall, such as other soft tissue tumors, pancreatic
      pseudocysts and gastric duplication cysts. In conclusion, every cystic tumor in
      the upper abdomen for which a diagnosis and origin cannot be established should
      be explored by surgery.

PMID- 10948738
TI  - [Do guidelines bring an improvement in the perioperative course? A study of
      perioperative antibiotic prophylaxis].
AB  - INTRODUCTION: Although the effectiveness of perioperative antibiotic prophylaxis
      is proven, it is not used adequately. The aim of this study was to evaluate
      whether hospital-based guidelines are useful tools to improve the management of
      perioperative antimicrobial prophylaxis. MATERIAL: In a retrospective study the
      actual quality of perioperative antibiotic prophylaxis as given by the criteria
      choice of drugs, dosage, timing, continuation and 2nd dose after > 3 h was
      evaluated. After information and establishment of adequate guidelines we started
      a prospective analysis to test compliance and rate of adequate prophylaxis.
      Differences were calculated according to the chi 2-test with P < 0.05
      significance niveau. RESULTS: The percentage of cases in which antibiotics were
      indicated but not administered was reduced from 15.5% to 8.4%. Compared to the
      result of the retrospective analysis, the prospective study showed a
      significantly higher percentage of adequately administered antibiotics (35.7% vs.
      63.5%). This was mainly due to the compliance with dosage recommendations and to
      the 2nd dose in longer surgical procedures. DISCUSSION: Guidelines lead to a
      significant improvement in perioperative antibiotic prophylaxis. To increase this
      effect, further approaches such as integration of guidelines into computer-based
      systems should be evaluated.

PMID- 10948739
TI  - [Health-related and disease-specific quality of life assessment after
      laparoscopic repeated fundoplication].
AB  - PURPOSE: In recent years, the efficacy of laparoscopic antireflux surgery has
      been well-documented with quality-of-life data. The aim of the present study was
      to describe the efficacy of laparoscopic redo-surgery using health-related and
      disease-specific quality-of-life data. METHODS: A sample of 30 patients with mean
      age of 56 years underwent laparoscopic refundoplication. In 18 patients the
      primary antireflux procedure was performed by the open technique. In 12 cases the
      primary intervention was performed laparoscopically. To evaluate quality-of-life
      the German SF-36 Health Survey and the Gastrointestinal Quality of Life Index
      (GIQLI) were used and given to all patients before and 3 months and 1 year after
      redo-surgery. RESULTS: Before surgery, in two (physical functioning, role
      physical) out of 8 dimensions of SF-36 the values have not decreased
      significantly (P < 0.05) compared to healthy individuals. Three months after
      laparoscopic redo-surgery all reduced dimensions improved significantly (P <
      0.05). One year after surgery all dimensions are stable and comparable to a
      healthy population. Prior to redo-surgery, the mean GIQLI was 86.7 points and
      improved significantly (P < 0.05) to 121.6 and 123.8 points (3 months and 1 year
      after refundoplication) and reached an equivalent level of comparable healthy
      individuals (122.6 points). There are no significant differences between patients
      with an open and laparoscopic initial antireflux procedure at all times of
      measurement. Postoperative data of only 28 patients were included because in two
      patients conversion was necessary due to operative problems. CONCLUSION: Because
      of these results laparoscopic refundoplication can be discussed as an effective
      method of treatment after failed primary antireflux procedure. Laparoscopic redo
      surgery normalizes objective outcome criteria and also improves quality of life.

PMID- 10948740
TI  - [Adenocarcinoma in a tail-gut cyst: a rare cause of recurrent perianal fistula].
AB  - A 58-year-old woman was initially externally diagnosed in 1983 with a presacral
      mass, which was subsequently treated as an abscess. Thereafter, the patient
      experienced recurrent perianal fistulas. Further diagnostic studies revealed a
      cystic tumor, considered to be an epidermoid cyst, which was located in the
      inferior pelvis and was consequently removed. Histologically, cystic scar tissue
      was found with a highly differentiated adenocarcinoma which measured 4 cm. Later
      on, the patient again experienced perianal fistulas originating from a renewed
      presacral mass. As a result, an abdominal-perianal rectum extirpation and a
      partial resection of the sacrum with placement of a descendostomy were done.
      Histologically, adenocarcinoma tissue was found at the base of a tail-gut cyst.
      One year following her operation, the patient is free from any complaints and
      relapses. The tail-gut cyst is a very rare entity which arises from the
      inadequate involution of the tail-gut during embryonal development. A malignant
      transformation occurs in 10% of the cases. In the case of recurrent perianal
      fistulas and cystic masses between the rectum and os sacrum or os coccygeum, a
      tail-gut cyst should be taken into consideration, the goal being its complete
      removal.

PMID- 10948742
TI  - [B. Wolfgarten, M. July: Puncture tracheotomy with single tracheal dilatation.
      Experience in 74 patients. Chirurg (2000) 71:63-65].

PMID- 10948741
TI  - [Does quantity mean quality? An analysis of 116,000 patients regarding the
      connection between the number of cases and the quality of results].
AB  - METHODS: Between 1993 and 1998 data of 27,000 patients with hip fractures and
      89,000 patients undergoing cholecystectomy were collected by the department of
      external quality assurance at the chamber of physicians of Westphalia-Lippe. The
      data were analyzed for the relationship between volume and outcome, specified as
      mortality and morbidity. Logistic regression was used to adjust the results for
      demographic and clinical risk factors. RESULTS: The risk-adjusted probability of
      death from cholecystectomy was 89% higher in the group of small volume clinics
      (less than 30 procedures per year) than in the group of large volume clinics
      (more than 120 procedures per year) (odds ratio 1.89; 95% CI 1.19-3.00).
      Mortality from hip fractures was 33% higher (odds ratio 1.33, 95% CI 1.09-1.63)
      for the group of small volume clinics (less than 15 procedures per year) than the
      group of large volume clinics (more than 45 procedures per year). Among the group
      of small volume hospitals were some with excellent results, but they are more
      likely to be found in the group of large volume hospitals. On the other hand
      there were some departments with poorer results in the group of large hospitals.
      CONCLUSIONS: There is no threshold for good results. In general there is an
      inverse relationship between volume and outcome. High volume, though, is not a
      substitute for good results. It is not possible to infer good quality from high
      volume alone. Small-volume departments should document quality of care and
      results thoroughly.

PMID- 10948743
TI  - [C. Neues, E. Haas: Modification of postoperative wound healing by showering].

PMID- 10948744
TI  - [Amputations and prosthesis fitting of the upper limbs].

PMID- 10948746
TI  - The history of polymyalgia rheumatica/giant cell arteritis.
AB  - Only two years separate the initial descriptions of polymyalgia rheumatica (PMR)
      by Bruce in 1888 and giant cell arteritis (GCA) by Hutchinson in 1890. However,
      the existence of an association between these two conditions was definitely
      accepted only in 1964. Even if PMR is generally accepted as a different disease
      from GCA, some authors deem PMR to be a manifestation of a generalised arteritis
      and use the term GCA to define PMR/GCA as a whole. The time has come to clarify
      this issue.

PMID- 10948745
TI  - [Error, stress and teamwork in medicine and aviation. A cross-sectional study].

PMID- 10948747
TI  - Classification/diagnostic criteria for GCA/PMR.
AB  - Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two common
      rheumatic diseases occurring in middle-aged and older persons. Their cause is
      unknown and in neither is there a single specific diagnostic test. As a result a
      combination of findings is needed for their diagnosis. The American College of
      Rheumatology has established criteria for the classification of GCA using two
      methods. These criteria are best used in research studies involving patients with
      a diagnosis of vasculitis. One method is based on the so-called traditional
      format. In this method the patient with vasculitis is classified as GCA if he/she
      manifests any 3 among the list of 5 criteria selected. The second method, the
      tree format or recursive partitioning method, starts with the clinical finding
      that best separates patients with GCA from others with vasculitis and then uses
      other criteria successively to point to a final decision regarding the presence
      or absence of GCA. Diagnostic criteria for GCA have not been formulated.
      Diagnostic criteria have been established for PMR by analysis of a series of
      patients, but in practice most rheumatologists use criteria established
      informally by consensus.

PMID- 10948748
TI  - Clinical features of GCA/PMR.
AB  - Giant cell arteritis (GCA) is a common vasculitis of unknown cause that affects
      persons in middle age and older. Its incidence rises with increasing age. The
      inflammatory lesions involve larger arteries that contain an abundance of elastic
      tissue. Although cranial symptoms such as headache, tender scalp, jaw
      claudication and visual symptoms are common, the disease presents in many
      different fashions, often with symptoms not directly related to the arteries.
      These latter presentations include fever, severe malaise, polymyalgia rheumatica,
      high erythrocyte sedimentation rate and anemia, thrombocytosis, sore throat, and
      hepatic dysfunction. GCA appears to have a self-limited course, but is also
      characterized by relapses and recurrences. Visual loss due to occlusion of the
      optic arteries is the most important early manifestation and aortic aneurysm is
      the most important late complication. Patients respond promptly to varying doses
      of glucocorticoids but drug side effects are common.

PMID- 10948749
TI  - Epidemiology of polymyalgia rheumatica.
AB  - OBJECTIVE: To review the data on the epidemiology of polymyalgia rheumatica
      (PMR), in particular geographical and temporal differences in incidence and its
      risk factors including the actinic hypothesis. METHODS: Evaluation of the
      literature. RESULTS: Epidemiological data show that the incidence of PMR varies
      between 12.7/100,000 in Italy and 112.6/100,000 in Norway with a geographical
      gradient of increased frequency in the northern hemisphere. The incidence of PMR
      and giant cell arteritis (GCA) have increased in recent years. This observation
      may be related to a greater awareness of the disease but also to real
      epidemiological changes. Risk factors for PMR/GCA include infections, smoking,
      sun exposure, and nulliparity. CONCLUSION: Epidemiological studies have helped to
      unravel the etiopathogenic factors at work in PMR/GCA. More data are needed on
      the correlation between the incidence of PMR/GCA and epidemics of infectious
      diseases and on environmental and biological risk factors.

PMID- 10948750
TI  - Human Parvovirus and giant cell arteritis: a selective arteritic impact?
AB  - Peak incidences of giant cell arteritis (GCA) following human Parvovirus
      epidemics were found in 2 previous epidemiological studies. The incidence of GCA
      [temporal arteritis and polymyalgia rheumatica (TA + PMR)] was studied before and
      after a major epidemic of human Parvovirus in 1994. Clinical data from the
      National Patient Register showed a significant inversion of the TA/PMR ratio
      during a 12-month period after an HPV epidemic. The inversion of this ratio was
      due to an increase in TA. The change in the ratio was most pronounced in the
      regions with the epicenter of the epidemic.

PMID- 10948751
TI  - Epidemiology of biopsy-positive giant cell arteritis: an overview.
AB  - Giant cell arteritis (GCA) is reported world-wide. However, the incidence varies
      greatly in different geographic regions with the highest incidence rates from
      Scandinavian countries and North American populations of the same descent. The
      etiopathogenesis of GCA is incompletely understood. Although data on a positive
      correlation between the occurrence of infection and the onset of GCA as well as
      rhythmic fluctuations in disease incidence have been reported, no statistically
      significant periodicity has so far been found regarding the annual incidence of
      GCA. Seasonal variations may indicate a role of infection or other environmental
      factors in the pathogenesis of GCA.

PMID- 10948752
TI  - The pathogenesis of giant cell arteritis: morphological aspects.
AB  - The light-microscopic, electron-microscopic and immunocytochemical
      characteristics of giant cell arteritis (GCA) have been investigated in a number
      of studies on temporal arteries. Arterial atrophy and calcification of the
      internal elastic membrane appear to be prerequisites for the evolution of the
      inflammatory process. Foreign body giant cells form close to calcifications,
      apparently without connection with other inflammatory cells and probably by the
      fusion of modified vascular smooth muscle cells. The foreign body giant cells
      attack the calcifications. Lymphocytes accumulate around them and may be found in
      pockets in their cell surface. This focal reaction is found in atrophic,
      calcified arterial segments in a minority of inflamed temporal artery biopsies.
      More commonly seen is a diffuse mononuclear attack of the vessel wall in atrophic
      as well as non-atrophic segments which leads to severe arterial dilatation.
      Langhans giant cells form by the fusion of macrophages in the diffuse
      inflammatory infiltrate. The fact that the diffusely inflamed arteries are
      markedly widened compared to the focally inflamed vessels suggests that the
      inflammatory process starts as a focal foreign body giant cell reaction directed
      at calcifications which in turn initiates a more diffuse and widespread
      inflammation.

PMID- 10948753
TI  - Giant cell arteritis and polymyalgia rheumatica: role of viral infections.
AB  - We performed a multicenter case-control study on incident cases of giant cell
      arteritis and polymyalgia, and tested for viruses known to induce multinucleated
      giant cells in human pathology. IgM directed against Human parainfluenza type 1
      virus were shown to be significantly associated with the onset of the disease in
      40% of the cases, versus 20% of the controls.

PMID- 10948754
TI  - Neurologic manifestations of giant cell arteritis.
AB  - Neurological manifestations are common in giant cell arteritis. Both the central
      and peripheral nervous system can be involved. The most dreaded manifestations
      are visual loss and stroke. Both frequently have premonitory symptoms, such as
      amaurosis fugax, blurry vision, diplopia, transient ischemic attacks, and jaw
      claudication. Although most of these manifestations occur prior to steroid
      therapy, they may also develop during the early phase of therapy, or during
      tapering of the dose of steroids. Earlier diagnosis, close monitoring and
      improving the treatment protocols may prevent mortality and improve morbidity in
      these cases.

PMID- 10948755
TI  - Giant cell arteritis as a cause of death.
AB  - It is not well known that giant cell arteritis can cause fatal complications due
      to rupture of aortic aneurysms or cerebral and myocardial infarctions. If
      corticosteroid treatment is started early, most of these complications can be
      avoided.

PMID- 10948756
TI  - Laboratory investigations useful in the evaluation of polymyalgia rheumatica
      (PMR) and giant cell arteritis (GCA).
AB  - The most useful investigation in supporting the clinical diagnosis of PMR/GCA is
      elevation of the erythrocyte sedimentation rate (ESR) or viscosity. Acute phase
      proteins, particularly CRP, are also elevated but in most cases are not more
      helpful than the ESR in either diagnosis or follow-up. The definitive
      investigation is the demonstration of giant cell arteritis histologically,
      usually from temporal artery biopsy. Elevation of alkaline phosphatase of liver
      origin is seen in one-third to one-half of patients and may lead to delay in
      diagnosis. Measurements of alpha 1-antichymotrypsin and IL-1 beta may be helpful
      in diagnosis and management but more studies are required.

PMID- 10948757
TI  - Von Willebrand factor in polymyalgia rheumatica and giant cell arteritis.
AB  - Patients with giant cell arteritis (GCA) and with polymyalgia rheumatica (PMR)
      have increased plasma levels of von Willebrand factor (vWF) even during
      corticosteroid therapy. The association between vWF, subclinical inflammation and
      cardiovascular complications in GCA/PMR remains to be investigated.

PMID- 10948759
TI  - Magnetic resonance imaging in the diagnosis of PMR.
AB  - The cause of musculoskeletal symptoms in polymyalgia rheumatica (PMR) is not
      clearly defined because joint synovitis may only partially explain the diffuse
      discomfort. MRI imaging of the shoulders, hip and extremities of patients with
      PMR has been analyzed. MRI showed that subacromial and subdeltoid bursitis of the
      shoulders and iliopectineal bursitis and hip synovitis are the predominant and
      most frequently observed lesions in active PMR. The inflammation of the bursae
      associated with glenohumeral synovitis, bicipital tenosynovitis and hip synovitis
      may explain the diffuse discomfort and morning stiffness.

PMID- 10948760
TI  - Doppler ultrasonography in the diagnosis of giant cell arteritis.
AB  - Ultrasonography of the temporal arteries detects characteristic signs of
      vasculitis with a high sensitivity and specificity: a hypoechoic halo due to an
      oedema of the artery wall and stenoses. The use of modern scanners with high
      resolution is essential. A halo has to be displayed in two planes. It is always
      circumferential. The colour intensity must not be too strong, otherwise the
      colour may cover the halo. A hypoechoic halo is also seen in large vessel giant
      cell arteritis at the axillary and brachial arteries and at the temporal arteries
      in polyarteritis nodosa.

PMID- 10948758
TI  - Polymyalgia rheumatica with normal erythrocyte sedimentation rate: clinical
      aspects.
AB  - Polymyalgia rheumatica is a relatively common syndrome of the elderly
      characterized by severe pain and stiffness in the neck shoulder and pelvic
      girdles, along with increased acute phase reactants. The current diagnostic
      criteria include as a requirement an erythrocyte sedimentation rate (ESR) higher
      than 30 or 40 mm/1 hr. Nevertheless, in several reports, a sizable proportion of
      patients with PMR, from 7% up to 22%, had an ESR that was either normal or
      slightly increased at the time of diagnosis, supporting the notion that an
      increased ESR should not be an absolute requirement for its diagnosis. This
      subset is characterized by a younger age, a less marked predominance of females,
      a longer diagnostic delay and a lower frequency of constitutional symptoms such
      as fever or weight loss. When determined, a majority of these patients had
      increased levels of C reactive protein. The recognition of this subset of
      patients with PMR and a low ESR can be very useful to the clinician, avoiding
      unnecessary suffering of the patients and the risks of ineffective therapy with
      nonsteroidal antiinflammatory drugs. To avoid the over-diagnosis of PMR in
      patients with a low ESR, we propose a set of criteria that can be easily applied
      in daily practice to patients with a clinical picture consistent with PMR but
      with a normal or slightly increased ESR.

PMID- 10948761
TI  - Imaging findings in extracranial (giant cell) temporal arteritis.
AB  - Patients with extracranial giant cell arteritis (GCA) present with occlusive
      arterial lesions that may be detected with multiple imaging modalities:
      arteriography, intravenous angiography (IV-DSA), CT scanning, and magnetic
      resonance angiography (MRA). The lesions often present with a typical
      arteriographic pattern of bilateral stenoses or occlusions with a smooth, tapered
      appearance in the subclavian, axillary and proximal brachial arteries. A few
      patients have aneurysmal lesions. Less commonly involvement may be found in the
      femoral arteries and their branches. Angiographic study of 65 patients (56 women,
      9 men; average age, 65) revealed involvement of the upper extremities in 61
      patients, and lower extremities in 13, while 9 had both areas affected. Detection
      of these lesions requires a diagnostic modality that depicts the vessel lumen
      such as: angiographic techniques, CT scanning with reconstructed images, and MRA.
      However, inflammation of the arterial wall cannot be detected by these means.
      Standard CT imaging with contrast enhancement, and certain MR sequences as well
      as ultrasound permit identification of the edema and inflammation of the vessel
      wall. This is an important marker for active disease.

PMID- 10948762
TI  - Elderly onset rheumatoid arthritis: clinical aspects.
AB  - The presentation, severity and prognosis of rheumatoid arthritis (RA) differ
      depending on the age of disease onset. Elderly onset RA (EORA: age of onset > 60
      years) has been reported to differ from younger-onset RA (YORA) by a more
      balanced gender distribution, a higher frequency of acute onset often associated
      with systemic features, more frequent involvement of the shoulder girdle and
      higher disease activity. To add to our knowledge of this disease, 101 EORA and 88
      YORA patients, not previously treated with DMDARs or steroids, were studied and
      compared, paying particular attention to the onset. The female to male ratio was
      higher in the YORA group (4.4:1 vs 1.6:1; p < 0.05). The disease duration was
      similar: 5.6 +/- 3.3 months in EORA and 7.9 +/- 3.8 months in YORA. EORA
      presented a more frequent acute onset (33.6% vs 13.6%; p < 0.05) especially if
      rheumatoid factor was absent. This subset also showed more frequent polymyalgic
      onset. Constitutional symptoms (fever, weight loss, fatigue) were more frequent
      in EORA patients without differences between seropositive and seronegative
      patients. The distribution of involved joints showed a significantly higher
      frequency of shoulder involvement in EORA (64% vs 38%; p < 0.05) and of feet
      involvement in YORA (25% vs 52%; p < 0.05). Hands and wrists were the most
      frequently involved joints in all patients.

PMID- 10948763
TI  - Distal musculoskeletal manifestations in polymyalgia rheumatica.
AB  - In polymyalgia rheumatica (PMR) the marked and distinctive symptoms of proximal
      aching and stiffness have tended to draw attention away from the distal
      musculoskeletal manifestations which also occur in this syndrome. Peripheral
      manifestations are present in about half of all cases of PMR and include joint
      synovitis, diffuse swelling of the distal extremities with or without pitting
      edema, tenosynovitis and carpal tunnel syndrome. Awareness of these findings will
      help to facilitate the proper diagnosis and institution of appropriate therapy
      for this disease.

PMID- 10948764
TI  - RS3PE syndrome: an overview.
AB  - More than ten years ago McCarty et al. described the RS3PE syndrome based on
      their study of 23 patients. Numerous additional cases have since been reported.
      In addition to the isolated or "pure" type which probably forms part of the
      clinical spectrum of polymyalgia rheumatica, inflammatory swelling with pitting
      edema of the dorsum of the hands and/or feet can be observed in different
      inflammatory rheumatic diseases as well as in haematological and solid
      malignancies.

PMID- 10948765
TI  - Corticosteroids in polymyalgia rheumatica--a review of different treatment
      schedules.
AB  - Low dose oral steroids (prednisolone 10-15 mg daily) are currently advocated for
      the treatment of uncomplicated PMR and the dose should be carefully adjusted in
      relation to disease activity. Intramuscular methylprednisolone has been shown to
      have a similar remission rate to oral steroids and a better side effect profile
      with respect to fracture rate and weight gain. Prophylaxis for osteoporosis at
      least with calcium and vitamin D should be initiated at the start of steroid
      therapy.

PMID- 10948766
TI  - Steroid sparing therapeutic approaches to polymyalgia rheumatica-giant cell
      arteritis. State of the art and perspectives.
AB  - The therapeutic approach to polymyalgia rheumatica (PMR) and giant cell arteritis
      (GCA) remains mainly based on corticosteroids. A few studies in PMR suggest a
      steroid-sparing effect with methotrexate in a subset of patients. No real
      alternative to steroids exists in GCA. Given the high chance of long-term
      treatment with corticosteroids in both diseases, randomized controlled trials
      with new immunosuppressive steroid-sparing drugs are eagerly awaited.

PMID- 10948767
TI  - Prevention of serious ophthalmic and cerebral complications in temporal
      arteritis?
AB  - PATIENTS: Five patients (mean age 81.6 years) developed bilateral blindness and 3
      additional patients suffered cerebral strokes (mean age 58 years) due to temporal
      arteritis. Bilateral blindness and strokes occurred despite corticosteroid
      treatment. RESULTS: In all patients with temporal arteritis, the diagnosis was
      made too late. Patients with bilateral blindness were referred to the Eye
      Hospital when one eye had already become blind. The delay between the first
      symptoms and blindness in one eye was (average) 7 weeks. The interval between
      blindness of the first and second eyes was (average) 5 days in 3 patients, and
      simultaneous blindness in both eyes occurred in 2 patients. The other eye also
      became blind despite mega-doses of prednisone in 3 patients. Three additional
      patients already showed neurological signs and symptoms at the beginning of the
      temporal headache. All 3 patients developed strokes after some weeks or months.
      The wrong diagnosis was made in the first examination(s) by the physician with
      patients having prodromal signs or symptoms, but who also showed signs of other
      vascular diseases (diabetes mellitus, hypertension or occlusion of the internal
      carotid artery) which masked the inflammatory disease of temporal arteritis.
      CONCLUSIONS: Early diagnosis is essential to prevent severe complications. In
      patients with a cerebral stroke the early neurological deficits are warning signs
      which means that one must observe the patient regularly at short intervals. After
      the diagnosis has been settled, treatment of the patients for several months with
      a high dosage of corticosteroids is mandatory.

PMID- 10948768
TI  - Corticosteroid-induced osteoporosis: pathogenesis and prevention.
AB  - In spite of their adverse side effects, natural and synthetic glucocorticoids
      (GCs) occupy a unique role in several fields of medicine. They are potent
      regulators of bone cell growth and differentiation and the actions on the
      skeleton and related tissues depend on several factors including the dose,
      duration of the exposure, the steroid type and the species. In humans some of the
      effects are indirect, such as the regulation of intestinal calcium absorption and
      PTH secretion. Other effects are due to the cellular response that occurs within
      the bone microenvironment. It has been well established in in vitro studies that
      GCs can promote osteoblast differentiation from mesenchymal osteoprogenitors both
      in rat calvarial culture and in adherent marrow stromal cells. Moreover, GCs are
      able to enhance expression of the mature osteoblast phenotype, increasing
      mineralized nodules, osteocalcin secretion, and the bone morphogenetic protein-6
      message level. However, the mechanisms by which GCs affect bone metabolism are
      still unclear. Recent studies with GCs on bone cells suggested that the
      production of cytokines and growth factors and the expression of their receptors
      may also be influenced by GCs. In fact, GCs are able to inhibit the synthesis of
      cytokines, such as interleukin-1 which stimulates bone remodeling by monocytes
      and macrophages. Moreover, osteoprotegerin, a recently cloned member of the tumor
      necrosis factor receptor family, is down-regulated by GCs, offering a possible
      interpretation for the induction of bone resorption by GCs. GC-induced inhibition
      of bone resorbing cytokines may contribute to explain the therapeutic actions of
      GCs in several diseases such as rheumatoid arthritis and myeloma. Furthermore,
      GCs modulate osteoclast recruitment, even if there is no clear explanation for a
      direct effect of GCs on osteoclastic precursors. Sustained stimulation of matrix
      degradation by isolated avian osteoclasts incubated with GCs has been reported,
      as well as cytotoxic effects on osteoclastic cells from neonatal rat long bones.

PMID- 10948769
TI  - The cardiovascular magnetic resonance machine: hardware and software
      requirements.
AB  - The flexibility of cardiac magnetic resonance imaging (MRI) includes faster
      imaging for applications such as stress tests, ventricular function, myocardial
      perfusion and coronary artery imaging. Faster imaging makes greater demands on
      the hardware and software. Although some cardiac imaging can be performed at 0.5
      T, some of the faster techniques demand the higher signal-to-noise ratio of
      higher main field, and fat suppression in cardiac images is more easily achieved
      at higher field. Main field inhomogeneity affects rapid imaging and performance
      in open-access magnets. High gradient performance, low eddy currents and surface
      receiver coils are essential for fast cardiac imaging and the hardware of these
      systems including interventional imaging is discussed. The use of ECG signals for
      prospective and retrospective cardiac synchronization of MRI is examined.
      Techniques for reducing the major problem of respiratory motion in MRI are
      surveyed. Flexibility in the computer architecture of the scanner and the
      electronics generating the pulse sequence and controlling data acquisition is
      vital in cardiac imaging, for retrospective cardiac gating, respiratory navigator
      controlled imaging and "real-time interactive" imaging in a similar manner to
      ultrasound imaging. Automated measurements from MR images remain under
      development. The pulse sequences and image display functions a cardiovascular MRI
      system should support for basic cardiac imaging applications and current clinical
      research areas are summarized.

PMID- 10948770
TI  - Aortic diseases--do we need MR techniques?
AB  - MR with its various imaging protocols including spin-echo MR-imaging, gradient MR
      imaging, flow-mapping and MR angiography is the ideal tool for noninvasive
      assessment of any kind of aortic diseases. The technique allows to image the
      aorta both in the thoracic cage and in the abdominal aspects better than any
      other tomographic image modality. With the capability of angiography after
      intravenous injection of gadolinium even the information previously only obtained
      from invasive catheter-based studies is now available within minutes after an
      intravenous injection. The overview manuscript compares various clinical settings
      of aortic diseases as assessed by various imaging modalities and highlights the
      capability of MR-imaging for aortic diseases both in the chronic and the acute
      clinical setting.

PMID- 10948771
TI  - Valvular heart disease: assessment of valve morphology and quantification using
      MR.
AB  - For clinical evaluation and decision-making in patients with valvular heart
      disease, the diagnostic armamentarium expands steadily. This evolution makes it
      difficult to choose the most appropriate approach for a specific valvular lesion.
      It may also reflect our uncertainty of what are the findings that best predict
      clinical outcome of patients, e.g. after surgery. Accordingly, for each type of
      valvular lesion, some pathopysiological considerations are stated in order to
      derive the most important measures that would allow optimal guidance of patients.
      Based on these considerations the value of an MR study is discussed for each
      valvular lesion. Newest advances in MR technology allow for highly accurate
      measurements of regurgitant volumes and hence, MR may be the method of choice for
      a quantitative evaluation of regurgitant valves. For assessment of stenosis
      severity, measurement of transvalvular pressure gradient is an appropriate
      measure and MR may not confer benefits over echocardiography, provided the
      ultrasound window is adequate (and stroke volume is in the normal range). With
      respect to surgical treatment, valvular morphology is of pivotal importance,
      particularly for the mitral valve, and echocardiography still appears to be the
      first line method. Little data relate lesion severity and/or morphology to
      clinical outcome. Conversely, the extent of cardiac adaptation to pressure-
      and/or volume-overload, i.e. ventricular remodeling, is a strong predictor of
      outcome, and is therefore most important for final judgement of the patient. For
      assessment of left and right ventricular remodeling, echocardiography typically
      provides all the necessary information. However, in special cases with discrepant
      findings, with inadequate ultrasound window, or in the preoperative work-up, MR
      may provide important information regarding cardiac adaptation to valvular
      lesion.

PMID- 10948772
TI  - Arrhythmogenic right ventricular dysplasia: MRI findings.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of
      unknown cause that is characterized pathologically by fibrofatty replacement of
      the right ventricular myocardium. Clinical manifestations include structural and
      functional malformations of the right ventricle, electrocardiographic
      abnormalities, and presentation with ventricular tachycardias with left bundle
      branch pattern or sudden death. The disease is often familial with an autosomal
      inheritance. In addition to right ventricular dilatation, right ventricular
      aneurysms are typical deformities of ARVD and they are distributed in the so
      called "triangle of dysplasia", i.e., right ventricular outflow tract, apex, and
      infundibulum. Ventricular aneurysms at these sites can be considered
      pathognomonic of ARVD. Another typical hallmark of ARVD is fibrofatty
      infiltration of the right ventricular free wall. These functional and morphologic
      characteristics are relevant to clinical imaging investigations such as contrast
      angiography, echocardiography, radionuclide angiography, ultrafast computed
      tomography, and magnetic resonance imaging (MRI). Among these techniques, MRI
      allows the clearest visualization of the heart, in particular because the right
      ventricle is involved, which is usually more difficult to explore with the other
      imaging modalities. Furthermore, MRI offers the specific advantage of visualizing
      adipose infiltration as a bright signal of the right ventricular myocardium. MRI
      provides the most important anatomic, functional, and morphologic criteria for
      diagnosis of ARVD within one single study. As a result, MRI appears to be the
      optimal imaging technique for detecting and following patients with clinical
      suspicion of ARVD.

PMID- 10948773
TI  - Congenital heart disease. Evaluation of anatomy and function by MRI.
AB  - With the increasing number of patients surviving after therapeutic intervention
      for congenital heart disease (CHD), accurate and frequent follow-up of their
      morphologic and functional cardiovascular status is required, preferably with a
      noninvasive imaging technique. Echocardiography, either transthoracic or
      transesophageal, has been the first choice for this purpose, and will probably
      keep that status, at least in a large segment of the CHD spectrum. Magnetic
      resonance imaging (MRI) is an established method for high-resolution
      visualization of cardiovascular morphology. In the past decade, newer MRI
      techniques have been developed that allow functional evaluation of CHD patients.
      Particularly the introduction of breath-hold imaging, contrast-enhanced MRA and
      user-friendly computer software for image analysis may move functional MRI of CHD
      from the science laboratory to clinical use. It is already evident that MRI is
      superior to echocardiography in certain areas of limited echocardiographic
      access, such as the pulmonary artery branches and the aortic arch in adult
      patients. But MRI has also a unique potential for accurate volumetric analysis of
      ventricular function and cardiovascular blood flow, without any geometric
      assumptions. If supported by increased cooperation between cardiologists and
      radiologists, MRI will grow into a useful noninvasive imaging tool that, together
      with echocardiography, will obviate the need for invasive catheter studies for
      diagnostic purposes.

PMID- 10948774
TI  - Magnetic resonance imaging in patients with cardiomyopathies: when and why.
AB  - Cardiac magnetic resonance imaging (MRI) is a noninvasive tool which is able to
      diagnose and differentiate cardiomyopathies in a single study. The assessment of
      essential information such as alterations of myocardial and ventricular geometry
      and function is possible with a high degree of accuracy and reproducibility,
      based on a small inter- and intraobserver variability. Thus, very small
      morphological and functional changes in different types of cardiomyopathy are
      detectable, thereby enabling the cardiologist to increase the safety of
      therapeutic decisions. Furthermore, MRI bears the potential to characterize
      tissue transformation in the different types of myocardial affections including
      ischemic, toxic, infiltrative or inflammatory forms.

PMID- 10948775
TI  - Quantification of right and left ventricular function by cardiovascular magnetic
      resonance.
AB  - Cardiac dysfunction is a major cause of cardiovascular morbidity and mortality.
      Accurate and reproducible assessment of cardiac function is essential for the
      diagnosis, the assessment of prognosis and evaluation of a patient's response to
      therapy. Cardiovascular Magnetic Resonance (CMR) provides a measure of global and
      regional function that is not only accurate and reproducible but is noninvasive,
      free of ionising radiation, and independent of the geometric assumptions and
      acoustic windows that limit echocardiography. With the advent of faster scanners,
      automated analysis, increasing availability and reducing costs, CMR is fast
      becoming a clinically tenable reference standard for the measurement of cardiac
      function.

PMID- 10948776
TI  - Magnetic resonance pharmacological stress for detecting coronary disease.
      Comparison with echocardiography.
AB  - Stress testing is the cornerstone in the diagnosis of patients with suspected
      coronary artery disease (CAD). Although exercise ECG remains the primary approach
      for the detection of ischemia in patients with chest pain syndromes, its
      sensitivity and specificity is limited and exercise ECG does not provide detailed
      information about the localisation and extent of CAD. Stress echocardiography has
      been used for the detection of ischemia for more than a decade and has become an
      increasingly popular noninvasive method for the detection of CAD. In experienced
      hands wall motion analysis based on stress echocardiography has proved to be as
      sensitive and specific for the detection of myocardial ischemia as scintigraphic
      techniques. Recent technical improvements, namely the availability of ultrafast
      imaging sequences with a significant reduction of imaging time have initiated
      several studies which examined the combination of pharmacological stress and
      magnetic resonance imaging (MRI) for the detection of suspected CAD. The most
      well developed stress-MRI technique is wall motion imaging during dobutamine
      stress. This technique is analogous to stress echocardiography, but MRI has the
      inherent advantages of better resolution, higher reproducibility and true long
      and short axis imaging with contiguous parallel slices. However, the clinical
      impact of MRI for the diagnosis of CAD is still low. Further technical
      developments including real time imaging and a reliable automated quantitative
      analysis of left ventricular function are required before stress-MRI becomes a
      serious challenge to stress-echocardiography in the clinical arena. Currently,
      only a few MRI facilities and physicians are dedicated to pharmacological stress
      testing with MRI and the future clinical impact of this promising technique will
      depend on its potential to provide information beyond myocardial function
      including perfusion, metabolism and coronary anatomy in form of a "one-stop"-shop
      for the cardiac patient.

PMID- 10948777
TI  - Cardiovascular magnetic resonance: myocardial perfusion.
AB  - There is growing evidence that the noninvasive assessment of myocardial perfusion
      with cardiovascular magnetic resonance is a valid and accurate tool for the
      assessment of ischemic heart disease and its introduction into routine clinical
      evaluation of patients is rapidly expected. Magnetic resonance measurements allow
      the evaluation of reversible and irreversible myocardial ischemia, the assessment
      of acute myocardial infarction, as well as the recognition and detection of
      viable myocardium. Magnetic resonance perfusion measurements are mainly performed
      with T1-shortening contrast agents such as gadolinium-DTPA either by visual
      analysis or based on the analyses of signal intensity time curves. For the
      detection of myocardial ischemia the first pass kinetics of a gadolinium-DTPA
      bolus and for the detection of myocardial necrosis and the definition of viable
      myocardium steady state distribution kinetics are assessed. Quantitative analysis
      of myocardial perfusion can be performed but requires complex modeling due to the
      characteristics of gadolinium-DTPA. Thus, semi-quantitative parameters are
      preferred. There is accumulating evidence in the literature that magnetic
      resonance imaging can be used for the detection of coronary artery stenosis with
      high diagnostic accuracy both with semi-quantitative or visual analysis.
      Myocardial infarction can be reliably detected and the infarcted area determined.
      Non-reperfused infarcted myocardium can be differentiated from reperfused
      myocardium by different enhancement patterns that correlates with viability.
      Cardiac magnetic resonance is a promising technique that can combine different
      functional studies during one examination, such as the assessment of wall motion
      and perfusion at rest and stress. With further improvements in analysis software
      magnetic resonance perfusion measurement may rapidly become a routine tool for
      the assessment of patients with coronary artery disease.

PMID- 10948778
TI  - Evaluation of myocardial viability by MRI.
AB  - Distinguishing between viable and non-viable myocardium is an important clinical
      issue. Several magnetic resonance (MR) techniques to address this issue have been
      proposed. Spectroscopy of phosphorus-31 and hydrogen-1 from creatine as well as
      imaging of sodium-23 and potassium-39 reflect information related to cellular
      metabolism. The spatial and temporal resolutions of these techniques are limited,
      however, by the small magnitude of the MR signal. Proton imaging techniques
      include examination of pathologic alterations in MR relaxation times (T1 and T2),
      wall thickness and thickening, cine MRI combined with low-dose dobutamine, first
      pass contrast enhancement patterns, and delayed contrast enhancement patterns. Of
      the proton imaging approaches, cine MRI combined with low-dose dobutamine is
      supported by the largest body of clinical evidence supporting the hypothesis that
      the technique yields useful information regarding myocardial viability. Recent
      data suggest that delayed contrast enhancement examines the transmural extent of
      viable myocardium irrespective of contractile function and that this technique
      should also be considered in a clinical setting.

PMID- 10948779
TI  - Coronary MR angiography: current status.
AB  - Since first described in the early 1990's, coronary magnetic resonance
      angiography (MRA) has evolved as a promising noninvasive modality for imaging of
      the coronary arteries and evaluation of coronary artery disease. Despite
      technical limitations, coronary MRA has established value for imaging of
      anomalous coronary arteries and assessment of bypass graft patency. Current
      research focuses on the development of optimal respiratory compensation
      strategies, improved spatial and temporal resolution and faster acquisition of
      image data. The accurate detection of stenoses and assessment of the severity of
      coronary atherosclerosis is presently being evaluated with large multicenter
      studies. With further technique enhancements and more clinical experience,
      coronary MRA is likely to become the dominant noninvasive modality in clinical
      cardiology.

PMID- 10948780
TI  - Interventional and intravascular MR angiography.
AB  - Magnetic resonance imaging (MRI) has a number of characteristics which make it
      attractive for guidance of intravascular therapeutic procedures, including high
      soft tissue contrast, imaging in any arbitrary oblique plane, lack of ionizing
      radiation, and the ability to provide functional information, such as flow
      velocity and volume per unit time. For MR guidance of vascular interventions to
      be safe, catheters and guidewires must be visualized relative to the vascular
      system and surrounding tissues. A number of approaches for making instruments
      visible in an MR environment are presented, including both passive and active
      techniques. Passive techniques depend on contrast agents or susceptibility
      artifacts, whereas active techniques, including MR tracking, MR profiling, and
      active field inhomogeneity, use some form of electrical coil built into the
      instrument. The potential for obtaining high-resolution images of the vessel wall
      using coils built into a catheter is also discussed. These images provide the
      capability to distinguish and identify various plaque components. The additional
      capabilities of MRI could potentially open up new applications beyond those
      currently performed under X-ray fluoroscopic guidance.

PMID- 10948781
TI  - Cardiac magnetic resonance spectroscopy: potential clinical applications.
AB  - MR spectroscopy is the only method for non-invasive detection of various aspects
      of cardiac metabolism in humans. While the 1H nucleus of water and fat molecules
      is the signal source for MR imaging, the MR spectroscopic technique allows for
      the study of a number of other nuclei, such as 13C, 19F, 23Na, 31P, 39K and 87Rb.
      Clinical applications presently are confined to the 31P nucleus. 31P-MR
      spectroscopy allows the non-invasive study of cardiac high-energy phosphate
      metabolites ATP and phosphocreatine. The phosphocreatine/ATP ratio is considered
      an index of the energetic state of the heart. Possible clinical indications
      include heart failure, valve disease and coronary artery disease. In heart
      failure, the phosphocreatine/ATP ratio is reduced and correlates with clinical
      severity, ejection fraction and prognosis. In mitral and aortic valve disease, a
      reduced phosphocreatine/ATP ratio may indicate the optimum timing for valve
      replacement. In coronary artery disease, a regional decrease of phosphocreatine
      during stress ("biochemical ergometry") may indicate local ischemia. Furthermore,
      absolute quantification of high-energy phosphates may allow diagnosis of
      myocardial viability. Major technical developments, leading to improved spatial
      and temporal resolution will be necessary to establish MR spectroscopy as a
      routine clinical tool.

PMID- 10948782
TI  - [Pacemaker therapy of hypertrophic obstructive cardiomyopathy. PIC (Pacing in
      Cardiomyopathy) Study Group].
AB  - Clinical management of patients with symptoms caused by pharmacological
      refractory hypertrophic obstructive cardiomyopathy must consider surgical
      myectomy, percutaneous transluminal septal myocardial ablation and implantation
      of a DDD pacemaker. Until now, no prospective, double blind, randomized studies
      have yet been carried out to determine the merits of each of these treatment
      alternatives. However, uncontrolled studies have shown that short
      atrioventricular delay dual-chamber pacing reduces outflow tract obstruction. Aim
      of the study was to investigate the results of the pacemaker therapy in a
      prospective, double blind randomized crossover procedure. All patients with
      hypertrophic obstructive cardiomyopathy included in this multicenter study were
      either refractory or intolerant to drugs and typically had pressure gradients
      higher than 30 mm Hg. In 83 patients, mean age 53 (18 to 82) years who responded
      favorably to a temporary pacing test, a DDD pacemaker was implanted. After echo-
      and echo-Doppler-based measurements of hemodynamic parameters the patients were
      randomized into 2 groups, those with an implanted pacemaker in the inactivated
      mode (AAI) and those with a pacemaker in the activated mode (DDD with optimized
      short AV delay). A crossover of these groups was performed after 12 and 24 weeks,
      respectively. Both objective parameters of echo including Doppler, and
      spiroergometry, and subjective parameters of angina, dyspnea, and quality of life
      were recorded. Additionally, subgroups based on age decades were analyzed. After
      12 weeks in the DDD mode, regardless of the randomization sequence, a decrease of
      the pressure gradient from 59 +/- 36 mm Hg (median) to 30 +/- 25 mm Hg was proven
      significant (p < 0.001). The endurance of the patients who, during screening,
      achieved less than 10 minutes of exercise by the Bruce protocol improved by 21%
      under DDD mode. The main symptoms, as measured by the NYHA classification,
      improved statistically significant from a mean of 2.4 to 1.7 for functional
      class, from a mean of 2.4 to 1.4 for dyspnea and from a mean of 1.0 to 0.4 for
      angina. Subgroup analysis showed improvements depended significantly upon age,
      with a marked improvement between the ages of 60 and 70, which was statistically
      significant as compared to other decades. Subjective improvements in the quality
      of-life of patients was measured using a specially developed questionnaire. These
      findings justify, by all means, the intention to implant a DDD pacemaker in older
      patients. In younger and/or such patients with elevated pressure gradients, the
      results of ongoing randomized studies comparing myectomy, PTSMA and pacing have
      to be considered.

PMID- 10948783
TI  - Underserved populations: the quality of their health services.

PMID- 10948784
TI  - Building pharmacoepidemiological capacity to monitor psychotropic drug use among
      children enrolled in Medicaid.
AB  - This study's objective was to develop a methodology to apply
      pharmacoepidemiological research toward understanding and improving psychotropic
      drug use among children enrolled in Medicaid. Using Kansas Medicaid data for 1995
      1996, we summarized drug claims, diagnoses, and demographics for children under
      20 who received at least one psychotropic drug prescription over either year. The
      sequence of steps needed to assure a quality improvement role is discussed. Use
      of key personnel in less regulatory and more clinical data applications is
      critical. Illustrating this approach, we found disproportionate numbers of
      children receiving psychotropic drugs who were young boys and larger numbers of
      white children receiving psychotropic prescriptions relative to their Medicaid
      enrollment than either African-American or Hispanic children. Medicaid agencies
      can expand epidemiological capacity to understand service use among segments of
      the population they insure as part of an overall commitment to improving quality.

PMID- 10948785
TI  - Effect of a pharmacist-managed diabetes care program in a free medical clinic.
AB  - Diabetes care, morbidity, and mortality are usually worse in poor minority
      populations compared with non-minority ones. This report evaluates evidence-based
      process and outcome measures of diabetes care in diabetic patients followed in a
      free medical clinic and compares them to published results. The following process
      measures compared favorably with measures of the general population: dilated eye
      and foot exams and measurements of glycated hemoglobin levels; concentrations of
      total cholesterol; fasting triglycerides and low density lipoprotein (LDL)
      cholesterol; and proteinuria (by dipstick). Process and outcome measures in 89
      diabetic patients referred to a Diabetes Management Program in which diabetes
      care was delivered by pharmacists following detailed algorithms (experimental
      group) were compared with measures in 92 diabetic patients who received diabetes
      care in the general clinic setting (control group). The patients in the
      experimental group had a slightly longer duration of diabetes and more
      microvascular and neuropathic complications, and more diabetic patients were
      taking insulin than were patients in the control group. All of the process
      measures listed above were more frequent in the experimental group. Compared with
      the control group, the initial glycated hemoglobin level (% +/- SE) in the
      experimental group was significantly (P < .001) higher (8.8 +/- 0.2 versus 7.9 +/
      0.2) but fell significantly (P < .03) more (-0.8 +/- 0.2 versus -0.05 +/- 0.3).
      The lack of a greater decrease in the glycated hemoglobin levels in the
      experimental group was not related to the inability of the pharmacists to follow
      the algorithms, the patients' refusal to follow the recommended medication
      adjustments, or the lack of appropriate self-monitoring of blood glucose in
      insulin-requiring patients. It was inversely related (r = -0.36, P < .03) to the
      number of missed visits, i.e., the greater the number of broken appointments, the
      less the glycated hemoglobin fell. In conclusion, diabetes care for a poor
      minority population in a free clinic setting can compare favorably to care in the
      general population. Pharmacists following detailed algorithms can enhance this
      care further. Administrative and support system changes that minimize the number
      of missed visits might further improve diabetes care in this population.

PMID- 10948786
TI  - Discussion of hormone replacement therapy between physicians and their patients.
AB  - We determined the relationship between patients' socioeconomic status and
      discussions with their primary care physicians about hormone replacement therapy
      (HRT) among women facing a decision about HRT within the prior year. The study
      included telephone interviews and medical record reviews. The setting was a
      general medicine practice of an urban teaching hospital in Boston, Mass. Women
      ages 50-65 visiting an academic teaching practice over a 3-month period were
      selected randomly. Of the 198 potential subjects, 118 (60%) agreed to participate
      in the survey. We examined discussions of HRT by women who had faced the decision
      to initiate HRT within the previous year. Women who were not on HRT or had been
      on therapy for less than 1 year were asked if they had discussed HRT with their
      physician in the past year. Socioeconomic factors and comorbidities were elicited
      during the survey and abstracted by chart review. The mean age of the 118
      participants was 57; 36% were black, 54% were white, 10% were other race, 17% had
      less than a high school education, 14% had diabetes, 31% had had a hysterectomy,
      and 7% had a history of breast cancer. Of the 80 women who did not use HRT or had
      used it for less than 1 year, 49 (61%) reported a discussion of HRT. In
      bivariable analysis, patients of white race were more likely to report a
      discussion than black patients (72% versus 43%, odds ratio [OR] 3.6, 95%
      confidence interval [CI] 1.3-9.7). After adjustment for history of osteoporosis
      and age, white patients were more likely to report a discussion (adjusted OR 3.3,
      95% CI 1.1-9.8). Further adjustment for the presence of 2 or more cardiac risk
      factors did not change the result. Neither level of education nor family income
      were significantly associated with HRT discussion. Compared with white women, the
      African-American women we studied were less likely to discuss HRT with their
      physicians. Further study is needed to determine whether the failure to discuss
      HRT is due to failure to initiate a discussion on the part of patients,
      physicians, or both.

PMID- 10948787
TI  - Commentary: quality of alcohol, drug, and mental health services for American
      Indian children and adolescents.
AB  - American Indian children and adolescents suffer from a high prevalence of
      alcohol, drug, and mental (ADM) disorders. Unfortunately, the systems of services
      for these children and youth have never been able to address adequately their
      mental health needs. Thus, the revolutionary changes now taking place within
      these service systems, in particular the marked increase in the direct provision
      of services by Indian tribes and organizations, provides a unique opportunity to
      address these historical shortcomings. In this paper, we describe our existing
      knowledge concerning the quality of ADM services for American Indian children and
      adolescents and their critical sociodemographic, sociocultural, and epidemiologic
      contexts. We then consider the implications of these studies for improving the
      quality of care as well as its measurement and monitoring.

PMID- 10948788
TI  - A case study in assessing an ethnically diverse community-based aging population:
      a multimethod approach.
AB  - Obtaining useful information to improve services for older, multi-ethnic
      populations requires a nontraditional approach to assessing needs that can
      overcome both cultural barriers and natural suspicions about research. This case
      study describes a multimethod needs assessment conducted in a large senior
      housing facility, where 58% of residents were non-English-speaking. Methods of
      data collection were both qualitative and quantitative. Data were gathered by
      focus groups, interviews, and a written survey (N = 874) on topics of need for
      personal care assistance, level of assistance required for instrumental
      activities of daily living, and mobility. Qualitative inquiry yielded information
      about facilities and safety, and culturally specific needs, particularly
      communication. The case study concludes by discussing how the research findings
      translated into on-site programmatic changes, and delineating the factors that
      contributed to the success of this approach.

PMID- 10948789
TI  - Patient-centered quality measures for Asian Americans: research in progress.
AB  - We aim to develop and validate a questionnaire that examines quality of care from
      the patient's perspective for limited-English-proficient Asian Americans (AA) of
      Chinese and Vietnamese descent. We will conduct focus groups of patients to
      identify issues important to them, with an emphasis on communication and access
      to care. We will then draft a questionnaire and test its validity using standard
      survey research methods and direct observation of patient-provider encounters.
      Subsequent field testing will involve face-to-face patient interviews 1 month
      after an outpatient visit. We will evaluate alternate modes of administration to
      test feasibility and to maximize response. The result of our study will be a
      validated, culturally sensitive, patient-centered instrument that measures health
      care quality for limited-English-proficient AA patients. Our research will
      provide a template for developing future quality measures for other vulnerable
      populations.

PMID- 10948790
TI  - Facility effects on racial differences in nursing home quality of care.
AB  - This paper reviews the literature on racial/ethnic differences in nursing home
      quality, segregated access to nursing home care, and organizational and community
      factors that may influence access and quality of care. We present illustrative
      data on county demographics and the racial mix of African American residents in
      nursing homes in these counties for a sample of four states. We also briefly
      describe plans for multilevel modeling to test variation in racial/ethnic
      disparities in care as a function of nursing home structures and processes and
      community context.

PMID- 10948792
TI  - Viral meningitis associated with increase in echovirus type 13.

PMID- 10948791
TI  - Measuring quality of care for vulnerable children: challenges and
      conceptualization of a pediatric outcome measure of quality.
AB  - This article addresses conceptual and practical issues in the assessment of
      pediatric health care quality, outlines a conceptual model for measuring quality,
      and describes ongoing research to validate an outcome measure of health care
      quality for vulnerable children. Pediatric quality measurement is distinct from
      that for adults due to development, dependence, differential epidemiology,
      demographic factors, and differences between the child and adult health services
      systems. A noncategorical approach to quality measurement, rather than one based
      on illness status or specific condition, is necessary to adequately measure
      quality for the majority of children, both healthy and ill. One promising
      noncategorical measure of pediatric health care quality is health outcome,
      specifically health-related quality of life (HRQOL). The Pediatric Quality of
      Life Inventory (PedsQL), a brief, practical, reliable, valid, generic pediatric
      HRQOL measure, is a suitable candidate measure. Ongoing research to validate the
      PedsQL as an outcome measure of health care quality is described.

PMID- 10948793
TI  - Young people bear the brunt of increasing sexually transmitted infections in
      England.

PMID- 10948794
TI  - Predictors and outcomes of networking intensity among unemployed job seekers.
AB  - This study examined predictors and outcomes of networking intensity (i.e.,
      individual actions directed toward contacting friends, acquaintances, and
      referrals to get information, leads, or advice on getting a job) during the job
      searches of a sample of unemployed individuals. The study used a Big Five
      framework, in which extraversion and conscientiousness were associated with both
      higher levels of networking intensity and higher use of other traditional job
      search methods. Networking comfort (a procedure-specific constellation of
      evaluative beliefs depicting attitudes toward using networking as a job-search
      method) was positively related to networking intensity above and beyond the
      effects of personality. Networking intensity did not provide incremental
      prediction of unemployment insurance exhaustion, reemployment or reemployment
      speed, or job satisfaction when intensity of use of other job-search methods was
      considered.

PMID- 10948795
TI  - A comparison of correlation, calibration, and diagnosticity as measures of the
      confidence-accuracy relationship in witness identification.
AB  - The relationship between witness confidence and accuracy (CA) has traditionally
      been measured by the point-biserial correlation (rpb). Recently, 2 alternative
      indices for measuring the CA relation have been proposed, namely calibration and
      diagnosticity analyses (e.g., P. Juslin, N. Olsson, & A. Winman, 1996). In this
      study, the 3 measures were compared quantitatively using 52 independent data
      sets. The measures rpb and calibration were weakly correlated, whether computed
      across earwitness data sets, eyewitness data sets, or all data. Thus, when
      applied to the same data, these 2 measures sometimes yield different conclusions.
      A modest relation was observed between the rpb and the diagnosticity of
      confidence. Finally, calibration and degree of over- and underconfidence covaried
      with task difficulty, consistent with K. A. Deffenbachers' (1980) optimality
      hypothesis.

PMID- 10948796
TI  - Collective efficacy versus self-efficacy in coping responses to stressors and
      control: a cross-cultural study.
AB  - This study examined how cultural differences and efficacy perceptions influence
      the role of job control in coping with job demands. Perceiving higher control
      mitigated the effects of demands on psychological health symptoms and turnover
      intentions only among American bank tellers reporting high job self-efficacy.
      Among American tellers reporting low job self-efficacy, perceived control
      exacerbated the effects of demands. However, in a matched Hong Kong sample,
      collective efficacy interacted in the same way with control and demands as job
      self-efficacy had in the American sample. These differences appear to be
      explained by the individual attributes of idiocentrism and allocentrism that are
      linked to the societal norms of individualism and collectivism, respectively.

PMID- 10948797
TI  - Effects of task performance and contextual performance on systemic rewards.
AB  - Evidence from 2 samples of Air Force mechanics supported the hypothesis that
      contextual performance affects employees' career advancement and rewards over
      time. Results of hierarchical regressions controlling for experience showed task
      performance and contextual performance each predicted systemic rewards. Each
      facet explained separate variance in promotability ratings over 2 years. In both
      samples, contextual performance explained separate variance in informal rewards
      but task performance did not. Task performance explained incremental variance in
      career advancement 1 year later but contextual performance did not. Analyses
      using correlations corrected for unreliability suggest these results cannot be
      attributed to measurement error. Contextual performance still explained separate
      variance in informal rewards, and task performance explained distinct variance in
      career advancement a year later.

PMID- 10948798
TI  - The homogeneity assumption in differential prediction analysis: does it really
      matter?
AB  - In simulation studies, the F test for differences in regression slopes has tended
      to distort nominal Type I and II error rates when the 2 subgroup error variances
      exceeded a 1.50:1 ratio. This study examines the frequency and extent that this
      ratio is violated within data sets relevant to applied psychology. The General
      Aptitude Test Battery (GATB) validity study database contained ability data and
      overall job performance ratings. The Project A military database contained both
      ability and personality data, along with job performance factor scores and an
      overall job performance rating. Results suggest that subgroup (White-Black, male
      female) error variances are often homogeneous enough to support F test results
      from past empirical work. Enough heterogeneity was found, however, to urge
      applied psychologists investigating differential prediction to explore their data
      and consider the possibility of alternative statistical tests.

PMID- 10948799
TI  - Postdictors of eyewitness errors: can false identifications be diagnosed?
AB  - Eyewitness researchers have "postdicted" identification accuracy using witness
      confidence (S. L. Sporer, S. Penrod, D. Read, & B. Cutler, 1995), response
      latency (S. L. Sporer, 1993, 1994), and endorsement of statements consistent with
      using relative versus absolute judgment strategies (D. Dunning & L. B. Stern,
      1994; R. C. L. Lindsay & K. Bellinger, 1999). All of these measures were
      collected from 321 introductory psychology students who had viewed a staged crime
      and completed a lineup identification task. Some participants received feedback
      after identification (G. L. Wells & A. L. Bradfield, 1998). Lineup fairness was
      also used as a postdictor of eyewitness accuracy. Discriminant function analysis
      indicated that 75.2% of choosers and 63.0% of nonchoosers were correctly
      classified. Decision time and lineup fairness were the best postdictors of
      accuracy. The implications for postdicting real eyewitness decisions are
      discussed.

PMID- 10948800
TI  - Relationships between ability requirements and human errors in job tasks.
AB  - This article describes a program of research investigating the relations between
      abilities required to perform job tasks and human error probabilities while
      performing these tasks. Study 1, using objectively derived human errors made in
      performing Air Force job tasks, evaluated an ability-requirements classification
      methodology and found that error rates were related to the numbers, types, and
      levels of different abilities required. In Study 2, subject matter expert panels
      used the methodology to identify the ability requirements of tasks in 2 different
      jobs found in each of 2 types of nuclear power plants. This study, using a task
      anchored scale of human error probability, replicated the findings of Study 1,
      identified 2 ability requirements that cross-validated in predicting task-error
      probabilities across both jobs and plants, and identified other abilities
      specific to error probabilities in each job.

PMID- 10948801
TI  - Improving group decisions by better pooling information: a comparative advantage
      of group decision support systems.
AB  - This study compared a group decision support system (GDSS) with face-to-face
      (FTF) group discussion on characteristics of information exchange and decision
      quality. Participants given conflicting information tended to share more of their
      unique data and engaged in more critical argumentation when using the GDSS than
      when meeting FTF. Conversely, when information was consistent among members,
      there were no such differences between FTF and GDSS groups. The GDSS groups
      significantly outperformed the FTF groups in agreeing on the superior hidden
      profile candidate, especially when there was a lack of prediscussion consensus.
      Individual-level analyses revealed that members of GDSS groups that did not have
      a prediscussion consensus tended to experience stronger preference shifts toward
      the group's consensus decision.

PMID- 10948802
TI  - The effects of peer review and evidence quality on judge evaluations of
      psychological science: are judges effective gatekeepers?
AB  - Scientifically trained and untrained judges read descriptions of an expert's
      research in which the peer review status and internal validity were manipulated.
      Seventeen percent of the judges said they would admit the expert evidence,
      irrespective of its internal validity. Publication in a peer-reviewed journal
      also had no effect on judges' decisions. Training interacted with the internal
      validity manipulation. Scientifically trained judges rated valid evidence more
      positively than did untrained judges. Untrained judges rated a study with a
      confound more positively than did trained judges. Training did not affect judge
      evaluations of studies with a missing control group or potential experimenter
      bias. Admissibility decisions were correlated with judges' perceptions of the
      study's validity, jurors' ability to evaluate scientific evidence, and the
      effectiveness of cross-examination and opposing experts to highlight flaws in
      scientific methodology.

PMID- 10948803
TI  - A group-level model of safety climate: testing the effect of group climate on
      microaccidents in manufacturing jobs.
AB  - This article presents and tests a group-level model of safety climate to
      supplement the available organization-level model. Climate perceptions in this
      case are related to supervisory safety practices rather than to company policies
      and procedures. The study included 53 work groups in a single manufacturing
      company. Safety climate perceptions, measured with a newly developed scale,
      revealed both within-group homogeneity and between-groups variation. Predictive
      validity was measured with a new outcome measure, microaccidents, that refers to
      behavior-dependent on-the-job minor injuries requiring medical attention. Climate
      perceptions significantly predicted microaccident records during the 5-month
      recording period that followed climate measurement, when the effects of group-
      and individual-level risk factors were controlled. The study establishes an
      empirical link between safety climate perceptions and objective injury data.

PMID- 10948804
TI  - Reactions to two versions of affirmative action among whites, blacks, and
      Hispanics.
AB  - Houston-area Whites (n = 414), Blacks (n = 392), American-born Hispanics (n =
      162), and Hispanic immigrants (n = 177) evaluated a self-defined "typical"
      affirmative action plan (AAP) and a tiebreak AAP that applies under conditions of
      equal qualifications and underrepresentation. Whites preferred Tiebreak; Blacks
      and Hispanics preferred the typical AAP. The groups differed in beliefs about the
      procedures and fairness of affirmative action (AA), perceptions of workplace
      discrimination, and political orientations. Perceived fairness predicted support
      for both AAPs in all American-born groups, but the impact of other predictors
      varied greatly across AAPs and ethnic groups. The results clarify the bases for
      Whites' opposition to AA as they construe it. The results also underscore the
      importance of specifying the AAP procedures, of uncovering the predictors of AA
      attitudes among target-group members, and of conducting separate analyses in each
      ethnic community.

PMID- 10948805
TI  - Adaptability in the workplace: development of a taxonomy of adaptive performance.
AB  - The purpose of this research was to develop a taxonomy of adaptive job
      performance and examine the implications of this taxonomy for understanding,
      predicting, and training adaptive behavior in work settings. Two studies were
      conducted to address this issue. In Study 1, over 1,000 critical incidents from
      21 different jobs were content analyzed to identify an 8-dimension taxonomy of
      adaptive performance. Study 2 reports the development and administration of an
      instrument, the Job Adaptability Inventory, that was used to empirically examine
      the proposed taxonomy in 24 different jobs. Exploratory factor analyses using
      data from 1,619 respondents supported the proposed 8-dimension taxonomy from
      Study 1. Subsequent confirmatory factor analyses on the remainder of the sample
      (n = 1,715) indicated a good fit for the 8-factor model. Results and implications
      are discussed.

PMID- 10948806
TI  - Generalization effects of coping-skills training: influence of self-defense
      training on women's efficacy beliefs, assertiveness, and aggression.
AB  - Concern for personal safety is a pervasive stressor for many women. Developing
      competencies in physical self-defense may empower women to engage more freely in
      daily activities with less fear. This study assessed the effects of physical self
      defense training on multiple aspects of women's perceived self-efficacy and other
      self-reported personality characteristics. Training powerfully increased task
      specific (self-defense) efficacy beliefs as well as physical and global efficacy
      beliefs. Training increased self-reported assertiveness, and posttraining
      decreases in hostility and aggression were found on several of the subscales of
      The Aggression Questionnaire (A. H. Buss & M. Perry, 1992), indicating that
      training did not have an aggression-disinhibiting effect. In the experimental
      condition, most of the effects were maintained (and some delayed effects appeared
      at follow-up.

PMID- 10948807
TI  - Performance appraisal process and system facets: relationship with contextual
      performance.
AB  - Because appraisal-related interactions between supervisors and employees may
      influence more than task performance, the authors considered the potential
      effects of social and interpersonal processes in performance appraisal on
      contextual performance. They hypothesized that performance appraisal process and
      system facets were associated with employees' contextual performance as well as
      with their perceptions of appraisal accuracy. After controlling relevant
      variables, they found that appraisal process facets explained variance in
      contextual performance and perceived accuracy beyond that accounted for by the
      system facets. However, when the order of entry for the process and system
      variable sets was reversed, only for perceived appraisal accuracy, as
      hypothesized, did the system facets account for variance beyond that explained by
      the appraisal process facets.

PMID- 10948808
TI  - Latex allergy: a primary care primer.
AB  - Latex allergy has become an epidemic among healthcare workers. Other individuals
      who are frequently exposed to latex gloves or products containing latex have
      experienced latex hypersensitivity, as well. Identification of patients who have
      latex allergy is crucial to physicians in order to formulate a management plan.
      This article includes discussion of the basic background on latex preparation,
      hypersensitivity, occupational risks, and management of affected patients.

PMID- 10948809
TI  - Efficacy of a steroid nasal spray compared with an antihistamine nasal spray in
      the treatment of perennial allergic rhinitis.
AB  - Allergic rhinitis is a common disease with a lifetime prevalence of 20% among the
      United States population. The cost of medication alone to manage allergic
      rhinitis in the United States was estimated to be $3.1 billion. The two most
      commonly prescribed classes of medications are antihistamines and topical nasal
      steroids. The data on comparing the efficacy of a commonly used antihistamine
      (azelastine hydrochloride) with that of topical steroids, however, are
      conflicting. Therefore, the reported study was undertaken to determine the
      efficacy of azelastine with that of a topical nasal steroid (flunisolide) in
      treating patients for the symptoms of perennial allergic rhinitis. Forty-four
      subjects were enrolled in a double-blind, placebo-controlled study using Balaam's
      design. In one group, patients were treated with topical nasal corticosteroids or
      placebo. In the other group, patients were treated with the antihistamine nasal
      spray or placebo. Subjective data were collected by the use of questionnaires and
      a daily diary, which focused on nasal symptoms, sleep, and daytime sleepiness.
      The results demonstrated that the topical nasal corticosteroid performed
      superiorly to the antihistamine nasal spray in improving sleep, daytime
      sleepiness, sneezing, ocular and nasal pruritus, and nasal congestion. Thus, the
      topical nasal corticosteroid was found to be more effective than antihistamine
      nasal spray in reducing symptoms of allergic rhinitis. This study provides
      further support for the use of topical nasal corticosteroids as first-line
      treatment for perennial allergic rhinitis.

PMID- 10948810
TI  - Inhaled corticosteroid-induced bone loss and preventive strategies.
AB  - Systemic corticosteroids are known to cause adverse effects on bone loss and,
      with long-term use, may result in osteoporosis. There is evidence that inhaled
      corticosteroids at moderate to high doses may also induce bone loss. This article
      discusses the effects of inhaled corticosteroids on bone formation and
      resorption. It also offers preventive strategies to minimize bone loss associated
      with long-term use of inhaled corticosteroids.

PMID- 10948811
TI  - Karyotyping of Candida albicans and Candida glabrata from patients with Candida
      sepsis.
AB  - The aim of this study was to determine the relatedness of Candida strains from
      patients suffering from Candida septicaemia by typing of Candida isolates from
      blood cultures and different body sites by pulsed field gel electrophoresis (PFGE
      using a contour-clamped homogenous electric field, CHEF). We studied 17 isolates
      of Candida albicans and 10 isolates of Candida glabrata from six patients. Four
      patients suffered from a C. albicans septicaemia, one patient from a C. glabrata
      septicaemia, and one patient had a mixed septicaemia with C. albicans and C.
      glabrata. Eight isolates from blood cultures were compared with 19 isolates of
      other sites (stool six, urine four, genital swab four, tip of central venous
      catheter three, tracheal secretion one, sputum one). PFGE typing resulted in 10
      different patterns, four with C. albicans and six with C. glabrata. Five of the
      six patients had strains of identical PFGE patterns in the blood and at other
      sites. Seven isolates of a 58-year-old female with a C. glabrata septicaemia fell
      into five different PFGE patterns. However, they showed minor differences only,
      which may be due to chromosomal rearrangements within a single strain. Thus it
      appears, that the colonizing Candida strains were identical to the circulating
      strains in the bloodstream in at least five of six patients.

PMID- 10948812
TI  - Disc diffusion test in the identification of Candida species.
AB  - A total of 448 clinical isolates and seven reference strains of Candida species
      were tested for their susceptibility to a group of dyes and chemicals. All
      strains were also identified by conventional methods. The chemicals/dyes used in
      the disc diffusion tests were brilliant green, janus green, cycloheximide, fast
      green, rhodamine 6 G, ethidium bromide and 2, 3, 5 triphenyl tetrazolium
      chloride. Sensitivity to the chemicals was coded by a seven-figure code.
      Resistogram patterns obtained were found to be specific for each species. The
      disc diffusion test was found to be inexpensive, quick and gave reliable results
      within 18 h.

PMID- 10948813
TI  - Dermatophytosis due to Trichophyton violaceum in Tuscany from 1985 to 1997.
AB  - We describe 45 cases of dermatophytosis due to Trichophyton violaceum diagnosed
      in Tuscany from 1985 to 1997. Diagnosis was based on direct microscope
      mycological examination and culture. Nine of the 45 patients were Italian, eight
      of whom were born and resident in Tuscany; the others were Africans who
      contracted the infection in their country of origin. The first case in a non
      European was observed in 1985, but since 1991 isolation from foreigners has
      become more frequent. The increase in cases of infection by T. violaceum in our
      region is certainly linked to immigration. The cases of epidermomycosis in
      Tuscans suggests that the fungus has already become autochthonous.

PMID- 10948814
TI  - Antibodies to antigens of Histoplasma, Blastomyces and Candida in HIV patients
      and carriers in Nigeria.
AB  - Serum samples from 60 subjects with confirmed HIV-1 infection including 28 AIDS
      patients and 32 carriers were examined by immunodiffusion for precipitating
      antibodies to antigens of Histoplasma, Blastomyces and Candida. Seven of the
      subjects, four patients and three carriers, showed antibodies to histoplasmin
      prepared from mycelial cultural filtrate of Histoplasma capsulatum var.
      capsulatum and H. capsulatum var. duboisii although without any clinical signs of
      classical or African histoplasmosis. Another eight subjects comprising five
      patients and three carriers demonstrated antibodies to yeast cell antigen of
      Candida albicans; three of the patients had oral lesions clinically suggestive of
      Candida infection. None of the serum samples revealed antibodies to "A" antigen
      (yeast cell antigen) of Blastomyces dermatitidis.

PMID- 10948815
TI  - Microsporum gypseum complex in Madras, India.
AB  - In Madras, India, 312 soil samples were collected from different habitats and
      screened for the presence of keratinophilic fungi especially those belonging to
      the Microsporum gypseum complex.

PMID- 10948816
TI  - Erysipelas and tinea pedis.
AB  - During a 2-year period 30 adults were selected out of a group of patients
      diagnosed with erysipelas, who, except for tinea pedis, were apparently otherwise
      healthy patients. Clinical and epidemiological studies were performed to
      establish how tinea pedis and erysipelas are related. Thirteen of 30 patients
      with a diagnosis of erysipelas were found to have tinea pedis due to Trichophyton
      mentagrophytes and Trichophyton rubrum. In seven of the patients (23%) tinea
      pedis was found to be the unique predisposing factor for erysipelas. Tinea pedis
      may be a risk factor for streptococcal infections such as erysipelas, mainly in
      tropical countries, where tinea pedis is a frequent disease.

PMID- 10948817
TI  - Adherence in tissues of immunocompromised mice of a non-mycelium producing strain
      of Candida albicans.
AB  - A non-mycelial strain of wild-type Candida albicans strain 3153 A was produced by
      repeated subculturing on Sabouraud glucose agar, and maintained on yeast extract
      peptone-glucose medium resulting in hydrophobic cells at 26 degrees C and
      hydrophilic cells at 37 degrees C. The behaviour of cells of this strain was
      studied in male BALB/c mice, immunocompromised by treatment with cyclophosphamide
      and cortisone acetate. An ex-vivo assay of cell adherence to tissue sections of
      liver, spleen, kidney and lymph-nodes was used. The adherence of yeast cells at
      26 and 37 degrees C was predominantly produced by hydrophobic cells and was
      significantly greater in spleen and liver of immunosuppressed mice compared with
      the organs of control animals. Adhesion was observed in the white and red pulp as
      well as in the marginal zone of the spleen.

PMID- 10948818
TI  - An epidemic of tinea corporis caused by Trichophyton tonsurans among children
      (wrestlers) in Germany.
AB  - An outbreak of tinea corporis due to Trichophyton tonsurans among 46 children
      (aged 7-17 years) was investigated. Most of them were wrestlers. Thirty-one
      strains were identified by conventional methods, but proved to be problematic in
      15 isolates due to colony variation and reduced sporulation. They were identified
      as Trichophyton tonsurans by the use of molecular methods, for example, sequence
      comparison of the ribosomal internal transcribed spacer (ITS) region and
      polymerase chain reaction fingerprinting. No DNA polymorphisms were detected with
      any of the techniques used, suggesting clonal reproduction of the populations of
      the species and providing evidence for spatial and temporal stability of the
      lineage.

PMID- 10948819
TI  - Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebo
      controlled, double-blind study.
AB  - A clinical study was conducted to evaluate the effectiveness of lactoferrin,
      which is a protein component of cow's milk, in the treatment of tinea pedis.
      Doses of either 600 mg or 2000 mg of lactoferrin, or a placebo was orally
      administered daily for 8 weeks to 37 adults who were judged to have mild or
      moderate tinea pedis. Dermatological improvement and antifungal efficacy were
      assessed. In the analysis of all subjects, dermatological symptoms scores in all
      groups decreased but the differences were not statistically significant comparing
      the three groups. However, in the analysis limited to subjects with moderate
      vesicular or interdigital tinea pedis, dermatological symptoms scores in the
      lactoferrin-treated groups decreased significantly in comparison with the placebo
      group (P < 0.05). The organisms isolated were Trichophyton rubrum and
      Trichophyton mentagrophytes. A mycological cure was not seen in any of the
      subjects. In the 37 subjects there were no adverse events and no subject withdrew
      from the study because of an adverse event. These results suggest that orally
      administered lactoferrin can improve the dermatological symptoms in some
      subjects. The potential usefulness of lactoferrin as a functional food material
      for treating tinea pedis was seen for the first time in this study.

PMID- 10948820
TI  - Case reports. Disseminated cryptococcoses without cryptococcal antigen detection.
AB  - During the last decade cryptococcoses were most frequently diagnosed in AIDS
      patients, where serologically high amounts of glucoronoxylomannan (GXM) were
      detectable. Disseminated cryptococcoses without cryptococcal antigen detection is
      unusual. Between August and October 1998 disseminated cryptococcoses were
      diagnosed in three patients consecutively although cryptococcal antigen was not
      detectable. Only one of the patients was HIV infected.

PMID- 10948821
TI  - Case report. Rhodotorula rubra fungaemia due to use of indwelling venous
      catheters.
AB  - Rhodotorula has been an infrequent cause of infection in humans but there have
      been some case reports about this systemic yeast infection. In this article, a
      Rhodotorula rubra fungaemia due to an indwelling catheter in a 23-year-old woman
      who had been diagnosed with non-Hodgkin's lymphoma grade IV B is described.

PMID- 10948822
TI  - Association of Mycoplasma hominis and Ureaplasma urealyticum with some indicators
      of nonspecific vaginitis.
AB  - The purpose of this study was to determine the isolation rates of Mycoplasma
      hominis and Ureaplasma urealyticum from three populations of women and also to
      relate the presence of these microorganisms with some indicators of nonspecific
      vaginitis. Three hundred vaginal swabs were taken from delivery, pregnant and
      control (not pregnant) women. Cultures were done in E broth supplemented with
      arginine or urea. M. hominis was isolated in 5% at delivery, 12% from pregnant
      and 5% from control women and U. urealyticum was isolated in 21%, 31% and 28%
      respectively. There was statistical difference in the isolation rate of M.
      hominis in pregnant women respect to the other groups. Both microorganisms were
      more frequently isolated in women with acid vaginal pH, amine-like odor in KOH
      test, clue cells and leucorrhea. M. hominis was isolated in 17% and U.
      urealyticum in 52% from women with nonspecific vaginitis. M. hominis was isolated
      in 2% and U. urealyticum in 13% from women without nonspecific vaginitis.
      Although the presence of clue cells and amine-like odor in KOH test have
      relationship with Gardnerella vaginalis, these tests could also suggest the
      presence of these mycoplasmas.

PMID- 10948823
TI  - [Isolation of Mycoplasma bovis during an outbreak of bovine mastitis at a dairy
      farm in the province of Buenos Aires. 1st report in the Republic of Argentina].
AB  - Several mycoplasma species produce various diseases in different animal species.
      M. bovis has been described as the cause of mastitis, arthritis, pneumonia and
      infertility in cattle. Furthermore, this species has been the most frequently
      isolated agent producing bovine mastitis. The objective of this study was to
      isolate and typify mycoplasma strains from a clinical mastitis outbreak in a
      dairy farm of Buenos Aires Province. A total of 279 samples were studied (276
      from pooled quarter milk of cows with clinical mastitis that did not respond to
      antibiotic therapy, 1 from bulk tank milk and 2 preputial swabs from bulls). The
      isolated mycoplasma strains (n = 12) were further characterized by biochemical
      analysis, serological studies and electrophoretic analysis of the protein
      profiles (SDS-PAGE). Based upon these studies, the isolated strains were
      identified as Mycoplasma bovis. This is the first report of isolation of this
      microorganism in Argentina. Therefore the results described here could be very
      useful to improve mastitis control in dairy farms.

PMID- 10948825
TI  - [Trypanosoma cruzi: obtaining extracellular amastigotes and studying their
      development under different culture conditions].
AB  - This work describes a protocol to obtain pure populations of extracellular
      amastigotes of Trypanosoma cruzi. The amastigote stage was obtained by means of
      temperature changes and human plasma added to the culture medium. Epimastigotes
      (clon BraC15C2) were first grown in F69 medium at 27 degrees C during 96 h and
      then at 36.5 degrees C. After three subcultures of 96 h each at the latter
      temperature a subsequent incubation in the presence of 5% human plasma, was
      needed to obtain a population of amastigotes that could be maintained
      indefinitely in the F69 or F29 media. This amastigote population was similar
      morphologically to that obtained through other methods. The kinetic of growth
      depended on the culture medium used (F29 or Brain-Heart Infusion, BHI). When
      culture was incubated at 27 degrees C in both media, the pre-exponential and
      logarithmic phases of growth were observed at 72-96 h and 24-48 h respectively.
      The change in stage from amastigote to epimastigote dependent whether amastigote
      were subcultured or not. The growth of amastigotes in BHI medium at 36.5 degrees
      C did not occurred. The growth of amastigotes was similar to those observed at 27
      degrees C when F29 medium was used although the transformation to epimastigotes
      did not take place at this temperature. A population over 99% of amastigotes were
      maintained at 36.5 degrees C indefinitely by means of subcultures in F29 medium.

PMID- 10948824
TI  - Descriptive study of human and bovine tuberculosis in Queretaro, Mexico.
AB  - A 5-year retrospective study (1992-1996) to look at the situation of human
      tuberculosis was conducted in Queretaro, Mexico. Also, a 6-month study to
      determine the frequency of gross lesions in dairy cattle at slaughter, and a
      short experiment to evaluate the effect of sodium borate in the survival of M.
      bovis in lesions were carried out. The number of cases were 114 in 1992, 211 in
      1995, and 174 in 1996. Possible risk factors were: overcrowding, under-nutrition,
      previous cases of TB in the family, concurrent Diabetes mellitus, poor personal
      hygiene, smoking, and alcohol abuse. Eighty percent of the cases were pulmonary.
      The number of cases increase with age, from 5% in patients 10-year old or younger
      to 42% in patients 50-year old or older. Seventy-two percent were cured, and only
      6% die. Persistent coughing was by far the most observed clinical symptom. From
      112 acid-fast negative samples, 8.9% were positive by culture. From 1,201
      carcasses revised at slaughter, 17% presented TB-gross lesions. Ninety-six
      percent were localized lesions involving frequently a single organ, mostly
      retropharyngeal, mediastinal, mesenteric and mandibular lymph. From 102 lesions,
      95% were TB-compatible, and 79% were positive to isolation of M. bovis. Most
      affected animals were female > 2 years old. It was observed that keeping lesions
      in a 6% sodium borate solution does not affect the diagnosis of M. bovis by
      culture after 150 days.

PMID- 10948826
TI  - Efficacy of florphenicol premix in weanling pigs experimentally infected with
      Actinobacillus pleuropneumoniae.
AB  - The efficacy of a florfenicol premix was studied in weaning pigs experimentally
      inoculated with Actinobacillus pleuropneumoniae. Twenty five clinically healthy
      pigs were distributed into 3 groups; group A non-medicated, groups B and C orally
      medicated with 20 and 40 ppm of florfenicol respectively. The pigs were fed
      during 12 consecutive days and on day 5 all the groups were challenged with A.
      pleuropneumoniae serotype 1. All the animals in Group A developed clinical signs.
      Most of the pigs in the medicated groups maintained a good health status.
      Postmortem examination revealed severe pleuropneumonia in pigs from the control
      group and pneumonic lesions in 40% of the animals treated with 20 ppm of
      florfenicol. Development of pleuropneumonia was prevented in all the pigs
      medicated with 40 ppm of florfenicol. Actinobacillus pleuropneumoniae was
      recovered from the lungs of all control animals and from one pig of each of the
      medicated groups, however, the avidin biotin peroxidase (ABC-P) method detected
      the presence of the microorganism in all the animals. We demonstrated that
      medication with feed containing 40 ppm of florfenicol blocked efficiently the
      signs and lesions caused by A. pleuropneumoniae and increased the daily body
      weight gain.

PMID- 10948827
TI  - Frequency of Cryptococcus species and varieties in Mexico and their comparison
      with some Latin American countries.
AB  - Cryptococcosis frequency is increasing in Mexico. Few epidemiologic and clinical
      surveys exist even though 10-15% of patients with AIDS develop this mycosis. To
      know the situation about the prevalence and etiological agents of cryptococcosis
      in our country, a study including isolated Cryptococcus spp. strains took place
      from 1989 to August 1998. A total of 211 Cryptococcus spp. strains obtained from
      patients of diverse hospital centers in Mexico City were studied. This study
      describes cryptococcosis epidemiological data, in our country. C. neoformans was
      the dominant isolation (97.15%), followed by two C. albidus isolation and one C.
      uniguttulatus isolation. 92.5% of the strains was isolated from cerebral spinal
      fluid and the remaining were from bone marrow, blood, ganglion, sputum, bronchial
      lavage and liver biopsy. AIDS was the principal opportunistic factor (85%).
      Strains were found prevails in males (87.3%). It was found that the age groups
      where the disease appears most frequently are in the fourth (37.5%) and third
      (33.8%) decade of life. Finally, the isolation frequency of the C. neoformans
      var. neoformans (vn) and var. gattii (vg) obtained in this study (vn 86.7%) and
      vg 10.4%) was compared with the ones registered in Argentina (vn 97.6%, vg 2.4%);
      Brazil (vn 83.3%, vg 15.8%); Cuba (vn 97.6%, vg 2.4%); Paraguay (vn 0%, vg
      100.0%); Puerto Rico (vn 100.0%, vg 0%) and Venezuela (vn 66.7%, vg 29.6%).

PMID- 10948828
TI  - Presence of keratinophilic fungi with special reference to dermatophytes on the
      haircoat of dogs and cats in Mexico and Nezahualcoyotl cities.
AB  - In order to study the presence of keratinophilic fungi with special reference to
      dermatophytes on the coat of dogs and cats living in the cities of Mexico and
      Nezahualcoyotl in the Metropolitan area of Mexico City, two hundred samples were
      collected from dogs and one hundred from cats by using the MacKenzie's tooth
      brush technique, they were processed by routine mycological methods for
      dermatophyte fungi, results were analyzed by means of the statistical packages
      SAS. There were isolated 67 and 90 keratinophilic strains from cats and dogs
      samples, respectively. The most commonly fungi isolated in pure culture in this
      study were Chrysosporium spp (25%), followed by Trichophyton terrestre (22%),
      Microsporum gypseum (5%), M. canis (4%), as well as mixed cultures like
      Chrysosporium spp. & M. gypseum (2%) and T. terrestre & T. mentagrophytes (1%).
      Keratinophilic fungi were found in higher numbers in the cat haircoat (67%) than
      in the dog's (45%) and the same was true with regard to dermatophytes with 12
      isolates out of a 100 samples in cats and 7 Isolates out of 200 samples from
      dogs. This may represent a health risk for humans in contact with a dermatophyte
      infected cat or dog.

PMID- 10948829
TI  - [Cyclospora cayetanensis infection. Laboratory diagnosis].
AB  - Cyclospora cayetanensis is an Apicomplexa protozoa which was found to cause
      gastroenteritis in humans in 1979. This paper reviews the laboratory diagnosis of
      the disease. The usefulness of direct examination of fresh fecal matter with
      special acid-fast stains is emphasized as well as the morphometric
      differentiation between this organism and other similar coccidia. The paper
      reviews the sporulation technique of Cyclospora cayetanensis for the recognition
      and differentiation of artifacts and green-blue algae. Another aspect discussed
      is the morphology of the parasite in histological sections and with
      electromicroscopic examination whereby tissue morphology changes caused by the
      microorganism can be identified. The experience of the Service and Laboratory of
      Parasitology of the Instituto Nacional de Pediatria of Mexico in the laboratory
      diagnosis of this protozoosis is described. The paper is oriented towards the
      inclussion of Cyclospora cayetanensis in the diagnostic protocols for the study
      of diarrheas in our health Institutions.

PMID- 10948830
TI  - Profits versus patients.

PMID- 10948832
TI  - End of the beginning.

PMID- 10948831
TI  - TSBME does regulate.

PMID- 10948833
TI  - A tale of two testicles.

PMID- 10948834
TI  - MedBytes.

PMID- 10948835
TI  - Undermining ERISA.

PMID- 10948836
TI  - Schoolyard scuffle.

PMID- 10948838
TI  - More choice, more voice.

PMID- 10948837
TI  - Who's writing the prescriptions?

PMID- 10948839
TI  - Reporting cancer.

PMID- 10948840
TI  - Radiology turf wars and antitrust law.
AB  - Nonradiologist health care providers have enjoyed the privilege of film
      interpretation without the assistance of radiologists. However, encroachment on
      the radiologist's turf of radiological image interpretation by nonradiologist
      physicians and radiographer technicians is reminiscent of recent antitrust
      battles between anesthesiologists and nurse anesthetists. Numerous antitrust
      issues are relevant to radiology; however, the scope of this article is limited
      to antitrust issues most relevant to radiology turf battles. Such battles often
      raise antitrust issues of group boycotts, tying arrangements, and exclusive
      contracts.

PMID- 10948841
TI  - Hypertension: the silent killer and the deadly quartet.

PMID- 10948842
TI  - Acute coronary syndromes. Time to re-think the old paradigm.

PMID- 10948843
TI  - Guidelines for young child feeding in the Caribbean--Part. II. Caribbean Food and
      Nutrition Institute.
AB  - This is the second of a three-part series by the Caribbean Food and Nutrition
      Institute (CFNI) on revised guidelines for young child feeding in the Caribbean.
      In Part 1, the guidelines dealt with the period before birth. These covered
      maternal nutrition and guidelines for promoting, protecting and supporting
      breastfeeding. This part covers the broad area of breastfeeding, nutrition of the
      newborn with low birthweight or other special requirements, and replacement
      feeding for infants who are not breastfed. It also discusses the introduction of
      complementary foods with emphasis on the continuation of breastfeeding for two
      years and beyond.

PMID- 10948844
TI  - Beta-adrenergic blockade in the treatment of congestive heart failure.
AB  - Although chronic sympathetic activation provides inotropic and chronotropic
      support to the failing heart, such activation may also have deleterious effects,
      including the direct cardiotoxic effects of catecholamines, activation of the
      renin-angiotensin-aldosterone system and an increase in myocardial oxygen demand.
      These observations indicate that beta-blockade might be beneficial in the
      treatment of heart failure. This suggestion is receiving growing support from
      clinical trials, which show that beta blockade improves the clinical and
      functional status of patients with heart failure resulting from dilated
      cardiomyopathy or ischaemic heart disease. These trials have also indicated beta
      blocking agents are much safer in patients with heart failure than was previously
      thought, provided that they are introduced at a low dose and titrated carefully.
      Newer beta blocking agents have ancillary properties that may be important in the
      treatment of heart failure. Bucindolol and carvedilol have vasodilating effects
      that may unload the failing heart, and carvedilol also has antiproliferative and
      antioxidant properties not shared by other beta blocking agents. Carvedilol is
      the only beta blocking agent that has reduced overall mortality in patients with
      heart failure in controlled clinical trials, and it also reduces hospitalization
      and improves the global assessment of patients. A large comparative trial against
      other beta blocking agents to confirm that these benefits are unique to
      carvedilol is about to be launched. Further clinical experience is required to
      determine the optimum use of carvedilol in the treatment of heart failure. The
      results obtained so far with carvedilol suggest that the management of heart
      failure is about to undergo a significant change.

PMID- 10948845
TI  - Spirituality in medicine.

PMID- 10948846
TI  - From Hippocrates to hypocrisy. A time to weep and a time to mourn.

PMID- 10948847
TI  - Two-year mortality and its determinants following acute myocardial infarction in
      Trinidad and Tobago.
AB  - The purpose of this study was to determine the occurrence of coronary artery
      disease risk factors in patients presenting with acute myocardial infarction
      (AMI) to a tertiary care institution in Trinidad and to determine the factors
      associated with increased mortality following AMI. All patients admitted to the
      Eric Williams Medical Sciences Complex (EWMSC) between January 1 and December 31,
      1996, with a diagnosis of AMI were identified using the hospital admissions and
      discharge diagnosis databases. Demographic, clinical and laboratory variables
      were extracted from the hospital case records of patients with confirmed AMI.
      Sixty-one AMI patients (38 men) were admitted during the study period. Mean age
      at admission was 60 +/- 11 years with an ethnic case mix of thirty-nine (62%) of
      East Indian descent, eight (13%) of African descent, twelve (20%) mixed ethnicity
      and three (5%) of Caucasian descent. Thirty patients (49%) were hypertensive.
      Thirty-two patients (53%) were diabetic and eighteen patients (30%) gave a
      history of cigarette smoking. The mean left ventricular ejection fraction was 53
      +/- 14%. The mean serum cholesterol from 29 patients was 228.2 +/- 49.0 mg/dl.
      Increasing age, female gender, an ejection fraction less than 40%, non treatment
      with streptokinase and in-hospital ventricular fibrillation were associated with
      poor survival. Multiple regression analyses identified three independent
      predictors of mortality. These were gender (p = 0.04), in-hospital ventricular
      fibrillation (p = 0.001) and an ejection fraction less than 40% (p = 0.02).
      Diabetes mellitus, hypertension, hyperlipidaemia and cigarette smoking were
      prevalent amongst patients presenting with AMI. Ventricular function was a major
      determinant of two-year mortality following AMI. Aggressive risk factor
      modification is recommended to prevent both first and recurrent coronary events.

PMID- 10948848
TI  - Management of acute myocardial infarction in the public sector in the Bahamas.
AB  - In 1996 and 1997, 52 patients were admitted to the Princess Margaret Hospital,
      Nassau, Bahamas, with a confirmed diagnosis of acute myocardial infarction (AMI).
      The average time to presentation after the onset of symptoms was 18 hours, with
      56% of patients presenting within 12 hours. Risk factors identified for ischaemic
      heart disease were hypertension (77%), obesity (62%), diabetes mellitus (35%),
      tobacco smoking (25%), a family history of coronary artery disease (17%) and
      hypercholesterolaemia (8%). Medications administered in the treatment of AMI
      included oral nitrates (96%), intravenous heparin (90%), beta-blockers (65%),
      morphine (15%), thrombolytic agents (8%) and lignocaine (4%). In hospital post
      myocardial infarction complications were angina (23%), arrhythmias (12%) and
      cardiac failure (10%). The average hospital stay was eight days, with a mortality
      rate of 19%. These results show that there is considerable room for improvement,
      particularly in the use of thrombolytic therapy, to ensure that all patients
      receive optimal acute and post myocardial infarction care.

PMID- 10948849
TI  - Profile of uncontrolled hypertensive patients attending the Specialist
      Hypertension Clinic, University Hospital of the West Indies.
AB  - The purpose of this study was to describe the knowledge of hypertension, its
      management, anthropometric measurements, blood pressure (BP), medication use, and
      current lifestyles of patients with persistent hypertension. Patients (n = 80)
      attending the Specialist Hypertension Clinic at the University Hospital of the
      West Indies (UHWI) who had a baseline systolic BP > 140 mmHg and/or a diastolic
      BP > 90 mmHg were invited to participate in the study. Blood pressure, height,
      weight, waist and hip circumferences were measured. Body mass index (BMI) and
      waist/hip ratio (WHR) were calculated. A pretested questionnaire with 40 items
      eliciting demographic data, level of activity, dietary habits, knowledge of
      hypertension, medication compliance, use of alternative medicines, and substance
      use was administered to each participant. Mean BMI for men was 27.65 (95% CI 25.7
      29.6); mean BMI for women was 30.89 (95% CI 26.1-35.7). In men, there was an
      association between BMI and WHR, r = 0.62, p < 0.05, an association between BMI
      and diastolic BP and a negative association between BMI and activity level (r = 
      0.42, p < 0.05). There was also an association between systolic BP and substance
      use (r = 0.41, p < 0.05). Although the majority of both men and women were
      classified as obese, only 12% of men and 7% of women recognized diet and
      overweight as contributing to high blood pressure. Reported diets tended to be
      high in fat, salt and meats and low in vegetables and fruits; the majority of the
      participants were sedentary. Medication compliance was good, with a mean of only
      four days of medications missed per month. These findings suggest that to lower
      blood pressures in this population, the use of nonpharmacologic therapy involving
      lifestyle changes such as improved diet, weight loss and increased physical
      activity will be important.

PMID- 10948850
TI  - Lessons from reporting 100,000 Jamaican electrocardiograms.
AB  - The screening programme of the Heart Foundation of Jamaica has found hypertension
      in 71% of women and 47% of men. Of these patients, 13% were newly discovered
      hypertensives. Left ventricular hypertrophy was present in 18% of hypertensive
      women and in 27% of men. Inadequate control of raised blood pressure was a
      frequent finding. Ischaemic electrocardiographic (ECG) changes were only found in
      4% of the 14,739 patients seen in the past two years but this is an
      underestimation of the prevalence of ischaemic heart disease. Arrhythmias seen
      over 15 years were usually benign, of sinus origin or ectopics in the absence of
      heart disease. Uncontrolled atrial fibrillation remains the most serious
      arrhythmia encountered and usually in hypertensive patients. Obesity found in 80%
      of women is a problem requiring public education. 'Silent' ischaemia in diabetic
      and left ventricular hypertrophy in hypertensive patients indicate the need for
      ECG examination in all newly diagnosed patients with either condition, and annual
      ECGs thereafter.

PMID- 10948851
TI  - Fatty acid composition and possible health effects of coconut constituents.
AB  - The link between excessive consumption of dietary saturated fats and coronary
      heart disease (CHD) is now well established. Because of its high content of
      saturated fatty acids, the consumption of foods containing coconut oil may
      therefore be a risk factor for CHD. While the fatty acid composition of coconut
      oil is well established, relatively little is known about the other constituents
      of coconut: the milk, water, cream and meat fractions. In this study, we show
      that while the water fraction is low in lipid content, the milk contains about
      24% of the fat content of oil and the cream and meat fractions about 34%. The
      other coconut constituents contain significant amounts of medium-chain
      triglycerides that are formed from fatty acids of chain length 8:0 to 14:0. It is
      these fatty acids, primarily 14:0, that are thought to be atherogenic. On the
      other hand, medium-chain triglycerides may be advantageous under some
      circumstances in that they are absorbed intact and do not undergo degradation and
      re-esterification processes. As a result, medium-chain triglycerides provide a
      ready source of energy and may be useful in baby foods or in diet therapy.
      Nevertheless, the possible negative effects of the saturated fatty acids and the
      absence of the essential fatty acid linolenic acid from all coconut constituents
      suggest that the coconut milk, oil and cream should not be used on a regular
      basis in adults.

PMID- 10948852
TI  - Penetrating injury to the great vessels. Case reviews and management approaches
      for West Indian surgeons.
AB  - Penetrating injury to the great vessels in the thorax is an increasingly common
      and alarming clinical scenario in the West Indies, and in Jamaica in particular.
      The management of these often life-threatening injuries involves careful surgical
      planning and prompt operation, with close adherence to the principles of adequate
      pre-operative stabilization and investigations, and intra-operative exposure and
      repair. While this may be more easily accomplished in tertiary care centres, the
      geographical realities of the West Indies require that every surgeon be familiar
      with these techniques. A report of the management of some recent cases is
      followed by a review of the subject and recommended treatment strategies are
      outlined.

PMID- 10948853
TI  - The role of C-peptide in the classification of diabetes mellitus.
AB  - We investigated twenty-one insulin-using patients, who had all been labelled as
      having insulin dependent diabetes mellitus (IDDM) or type 1 diabetes. Physicians
      have been erroneously using the term IDDM loosely to include all diabetics on
      insulin. The clinical criteria of the National Diabetes Data Group/WHO were used
      to reclassify these patients. Only thirteen were found to have IDDM and eight non
      insulin dependent diabetes mellitus (NIDDM). Using fasting C-peptide values, only
      five of the thirteen with clinical IDDM truly had IDDM, the others might have
      maturity onset diabetes of the young (MODY) or diabetes in the young. Of the
      eight with clinical NIDDM seven had normal to high C-peptide values; the lone
      patient with low C-peptide values had diabetes diagnosed at age 64 years. We
      conclude that the clinical classification of diabetes mellitus may be inaccurate
      and that C-peptide evaluation improves the accuracy of the classification.

PMID- 10948854
TI  - Effect of chloroquine prophylaxis on birthweight and malaria parasite load among
      pregnant women delivering in a regional hospital in Cameroon.
AB  - This survey was conducted between December, 1997 and August, 1998 at the Chantal
      Biya Maternity Section of the Ebolowa Provincial Hospital, Cameroon. A total of
      231 parturient mothers who gave birth to 232 neonates were included in the study.
      Ninety-five of them (41.1%) took anti-malaria prophylaxis (chloroquine) in the
      index pregnancy, and 136 (58.9%) did not. Both groups were similar with respect
      to socio-demographic characteristics except for educational level of the mother,
      which was significantly higher in the group on prophylaxis (chi 2 = 8.05; df = 2,
      p = 0.02). The overall prevalence of maternal parasitaemia was 37.2%. The group
      on chloroquine (TG) experienced a lesser parasitaemia (26.3%) than the non
      prophylactic group (CG) (44.9%, odds ratio (OR) = 2.28, CI = 1.24-4.19). The
      proportion of women with severe parasitaemia (> 4000 parasites/microliter) was
      also lower in the TG than CG (17.6% vs 7.3%; OR = 2.69, CI = 1.04-7.23). A modest
      reduction in low birthweight was found in the TG which was not significant (23.4%
      vs 16.0%; p = 0.16). In conclusion, chloroquine given to prevent malaria in
      pregnancy was found to be effective in reducing peripheral malaria parasitaemia,
      but improvement in birthweight could not be demonstrated. Among other factors,
      impaired biological activity of the drug at the level of the placenta where
      parasite sequestration frequently occurs might be the explanation. We recommend
      that further investigation be carried out in the study area to evaluate this
      finding, and if confirmed, institute appropriate changes in the present policy of
      chloroquine prophylaxis in pregnancy.

PMID- 10948855
TI  - Trends of AIDS in Guadeloupe (French West Indies) a longitudinal survey from 1988
      to 1997.
AB  - The study objective was to describe morbidity and mortality from HIV infection
      and the acquired immunodeficiency syndrome (AIDS) in Guadeloupe from 1988 to 1997
      and to evaluate survival and prognostic factors. The HIV infected patients
      database of Guadeloupe included 1771 adult patients up to December 31, 1997.
      Annual incidence of AIDS defining illnesses was calculated and compared using
      Poisson regression. Survival analysis with log-rank test and multivariate
      analysis with Cox's model were performed for patients with AIDS. At the end of
      December 1997, 599 cases of AIDS (33.8%) and 367 deaths (20.7%) were reported.
      For 32.1% of the patients, AIDS was diagnosed before inclusion. Incidence of most
      AIDS-defining events decreased over time, especially after the introduction of
      protease inhibitor therapy. Before the introduction of protease inhibitors in
      September 1996, overall median survival after AIDS diagnosis was 11.8 months (95%
      Confidence Interval (CI), 95% CI 10.2-14.1). After this date median survival
      increased to 17.8 months (95% CI 18.6-22.5) and probability of survival was
      significantly higher for patients treated with protease inhibitor in combination
      regimen (mean 19.0 months, Standard deviation (SD) 1.3) compared to those who
      were not (mean 7.9 months, SD 0.6, p < 0.0001). Prognosis factors of death after
      AIDS were older age (Relative Hazard, RH: 1.17, 95% CI 1.07-1.28), occurrence of
      two or more AIDS-defining events at the beginning of the disease (RH: 1.70, 95%
      CI 1.32-2.19), and a CD4 cell count less than 50/mm3 (RH: 2.33, 95% CI 1.71
      3.17). On the other hand, occurrence of AIDS during follow-up had a better
      prognosis (RH: 0.68, 95% CI 0.52-0.89) and protease inhibitor therapy was
      strongly associated with a longer survival (RH 0.26, 95% CI 0.13-0.53). We
      concluded that HIV infection in Guadeloupe was frequently diagnosed at the stage
      of AIDS. However, survival of patients and trends of major AIDS defining
      illnesses were more similar to the European pattern than to the Caribbean one, as
      a consequence of the availability of modern therapy.

PMID- 10948856
TI  - A sonographic study of kidney dimensions in a sample of healthy Jamaicans.
AB  - A sonographic study of 49 randomly selected healthy adult Jamaicans was conducted
      to establish a guide for renal dimensions in the population. The mean length of
      the right kidney was 9.7 +/- 0.7 cm and the left 10 +/- 0.7 cm. The left kidney
      was longer than the right in the overall group and in males. There was no
      difference in width between right or left kidneys in the group as a whole or
      within either gender. There was a significant association between the weight of
      males and width of their kidneys; however, this association was not seen in
      females. The lone association between weight of participants and renal length
      occurred in females and only with respect to the left kidney. Lengths and widths
      of kidneys were not associated with height in either gender. Renal surface area
      (RSA) was similar between the genders and also between right and left kidneys.
      Similarly, there was no significant association between renal length and body
      surface area (BSA) overall or within the genders. Renal index (RI) which is more
      reliable at assessing renal parenchymal mass than renal length alone was 20.92
      and 22.86 for the right and left kidneys, respectively, in males. Similarly, RI
      for the right and left kidneys in females was 23.76 and 25.54, respectively.

PMID- 10948857
TI  - Analgesia-sedation for day-case inguinal hernia repair. A review of patient
      acceptance and morbidity.
AB  - The objective of this study was to determine whether analgesia-sedation improved
      patient acceptance of day-case herniorrhaphy and to evaluate the extent of
      patient morbidity. A total of 98 patients (mean age 34 years, range 17-75 years)
      were studied before and after herniorrhaphy to determine their response to the
      procedure. All patients were unpremedicated and underwent herniorrhaphy using a
      Bassini repair technique with a standard local anaesthetic block. Sedation was
      obtained with titrated intravenous midazolam(Hypnovel, Roche Products Ltd.)
      without narcotic analgesia. Patients were evaluated with a simple questionnaire
      after surgery. The maximum dose of midazolam used was 5 mg (median dose 3.5 mg).
      Monitoring of vital signs with pulse oximetry during the operative period was
      routine though oxygen therapy was not required. All patients were able to walk
      without assistance and were discharged under responsible supervision. Operative
      morbidity was low (5%). Adverse reactions to the procedure such as nausea,
      vomiting and headache were not seen. In conclusion, conscious sedation allows
      amnesia to be achieved with low morbidity in the majority of patients undergoing
      local anaesthetic procedures. This should result in increased patient acceptance.

PMID- 10948858
TI  - Prevalence of risk factors in breast cancer patients at the University Hospital
      of the West Indies.
AB  - The records of one hundred and twenty consecutive patients diagnosed with
      carcinoma of the breast were examined between July 1996 and June 1999 in order to
      estimate the prevalence of established risk factors for this disease. Early
      menarche was present in 5.5% of patients, while 36 subjects (30%) were
      nulliparous and 6 (5%) had a first live birth after age 30 years. Four subjects
      had a previous biopsy with histological features of atypical hyperplasia. Fifteen
      subjects (12.5%) had one or more affected first degree relatives. Fifty-four per
      cent of subjects possessed none of the risk factors examined in this study while
      36% had a single risk factor and 10% possessed two risk factors. There was no
      significant clustering of risk factors in the group of patients aged thirty-five
      years or less. Larger studies should be encouraged to identify the risk factors
      which operate in our population and the degree to which published predictive
      variables are applicable.

PMID- 10948859
TI  - Autopsy rates at the University Hospital of the West Indies, 1968-1997.
AB  - Autopsy rates have not been reported at the University Hospital of the West
      Indies (UHWI) for more than three decades. Declining rates have been documented
      worldwide, and so we sought to define autopsy rates over the past three decades
      at UHWI. We conducted a retrospective analysis of the numbers and types of
      autopsies performed on deaths occurring in the institution, and calculated the
      relevant autopsy rates. The overall autopsy rate for the study period was 52.7%,
      with a statistically significant decline from 65.3% in the first decade to 39.3%
      in the third. The non-coroner's autopsy rate showed a concomitant decline from
      57.5% to 31.5%, while the coroner's autopsy rate remained stable with a slight
      increase from 28.1% to 29.1%. The factors that might have led to the decline of
      the autopsy are discussed.

PMID- 10948860
TI  - Hepatitis B-associated polyarteritis nodosa and hypertensive encephalopathy.
AB  - The case of a two-year-old boy with hypertensive encephalopathy secondary to
      Hepatitis B-associated polyarteritis nodosa is presented. Polyarteritis nodosa is
      a rare condition in children and its association with Hepatitis B viral infection
      is also rare.

PMID- 10948861
TI  - The human ruminant.
AB  - A five-month-old female infant was admitted to the Tropical Metabolism Research
      Unit with a weight for age of 49% and no evidence of oedema giving rise to a
      diagnosis of marasmus (Wellcome Classification). The underlying reason for her
      malnutrition was the Infant Rumination syndrome. This is an uncommon disorder
      which is thought to have a psychological component. A lack of awareness of the
      syndrome often leads to delay in diagnosis.

PMID- 10948862
TI  - Caroli's disease associated with a gastric diverticulum.
AB  - Caroli's disease or communicating ectasia of the intrahepatic biliary tree is a
      rare disease with unknown aetiology. The coexistence of this along with the
      uncommon condition of a gastric diverticulum has never been reported before. A
      deficiency in the fibromuscular matrix of both the bile ducts and the gastric
      wall may explain why these two pathologies may coexist in a single patient.

PMID- 10948863
TI  - Cardiovascular collapse in early pregnancy.

PMID- 10948864
TI  - Medical research at the Faculty of Medical Sciences, UWI, Mona Campus, 1960-1990.

PMID- 10948865
TI  - Massive virginal breast hypertrophy.

PMID- 10948866
TI  - The medical laboratory quality initiative.

PMID- 10948867
TI  - Prostate cancer conundrum.

PMID- 10948868
TI  - Exercise for heart failure?

PMID- 10948869
TI  - A new view of migraine.

PMID- 10948870
TI  - New heparin is no heavyweight.

PMID- 10948871
TI  - The glycemic index: a risk factor for heart disease?

PMID- 10948873
TI  - The Alzheimer's driving dilemma.

PMID- 10948872
TI  - COX-2 inhibitors cut risk of colon polyps.

PMID- 10948874
TI  - Causes of cancer: genes and environment.

PMID- 10948875
TI  - Living-donor liver transplants.

PMID- 10948876
TI  - Do statins build bones?

PMID- 10948877
TI  - Ever since I had a severe allergic reaction to a bee sting three years ago, I
      have been receiving allergy shots for insect venom. When, if ever, can I
      discontinue the injections?

PMID- 10948878
TI  - I have heard that eating green or leafy vegetables can be a problem when a person
      is taking the blood thinner Coumadin. Is this true?

PMID- 10948879
TI  - Surgical advances for Parkinson's.

PMID- 10948880
TI  - Taking the anxiety out of colon cancer screening.

PMID- 10948882
TI  - Middle management: stomach-slimming options.

PMID- 10948881
TI  - The special cholesterol concerns of women.

PMID- 10948883
TI  - Is there a difference between soy foods and soy supplements?

PMID- 10948884
TI  - Is my family physician qualified to diagnose Alzheimer's disease, or should I
      consult a neurologist?

PMID- 10948885
TI  - [The quality of nursing care: who is responsible?].

PMID- 10948886
TI  - [On HIV infection].

PMID- 10948887
TI  - [The fight against AIDS in Quebec: a collaborative process].

PMID- 10948888
TI  - [All you want to know about professional exposure to HIV].

PMID- 10948889
TI  - [An ethical tragedy].

PMID- 10948890
TI  - [Bomb alert: drug addiction and AIDS].

PMID- 10948891
TI  - [Caring for patients living with HIV/AIDS. An occasion to work on oneself].

PMID- 10948892
TI  - [Strategies for the effective care of patients with HIV infections].

PMID- 10948893
TI  - [Therapeutic observance, an active and progressive process].

PMID- 10948894
TI  - [Counseling during anonymous detection of HIV: a fitting role for the nurse].

PMID- 10948895
TI  - [Detection of HIV in pregnant women: a voluntary choice].

PMID- 10948896
TI  - [What to do after a needlestick injury in a doctor's office or in the hospital].

PMID- 10948897
TI  - [Octenidinedihydrochloride--a new antiseptic agent].

PMID- 10948898
TI  - [Bladder cancer--diagnosis and therapy].

PMID- 10948899
TI  - [When the optic nerve is sick].

PMID- 10948901
TI  - [English researchers have listened to surgeons at work. In the operating room
      orthopedists curse the most] [In Process Citation]

PMID- 10948900
TI  - [Progress in wound care].

PMID- 10948903
TI  - [Whose fault is it?] [In Process Citation]

PMID- 10948902
TI  - [Alternative methods of washing].

PMID- 10948905
TI  - [Prevention of allergies. New study: low allergen nutrition recommended also for
      children without risk of allergy] [In Process Citation]

PMID- 10948904
TI  - [Interview with Dr. Peter Schwandt: Not healing, but the prevention of disease
      will be our main mandate of the future].

PMID- 10948907
TI  - [Yes, yes--no, no: the courage to be reliable] [In Process Citation]

PMID- 10948906
TI  - [Autoimmune diseases of the thyroid and other organs] [In Process Citation]

PMID- 10948908
TI  - [Fatigue: cachexia in tumor patients--diagnosis and chances of intervention].

PMID- 10948909
TI  - [Fatigue in cancer patients--pathophysiology and therapeutic strategies].

PMID- 10948911
TI  - [Our quote: liberation for a natural death].

PMID- 10948910
TI  - [Creating a relationship with a suicidal client--from the nurse's viewpoint].

PMID- 10948912
TI  - [Bone marrow transplantation today].

PMID- 10948913
TI  - [Stem cell collection and donor registries].

PMID- 10948915
TI  - [Kidney failure and methods of treatment].

PMID- 10948914
TI  - [Care of burn victims at the intensive care unit].

PMID- 10948916
TI  - [Weakness is not shameful. The attempt always to be successful].

PMID- 10948917
TI  - [Ethics. The right to be born with a disease].

PMID- 10948918
TI  - [Partner in need].

PMID- 10948919
TI  - [Meeting of teachers for the nursing professions: the secret of success are the
      discussions during intermission].

PMID- 10948920
TI  - [International congress "Nursing diagnoses": nursing practice ought to be
      comparable internationally].

PMID- 10948921
TI  - [German congress of the Society for Incontinence Aid: Incontinence is not a
      minority problem].

PMID- 10948922
TI  - [Teaching students. 11. Shampooing in bed. Bedbound patients want to look well
      groomed too].

PMID- 10948923
TI  - [Language course for foreign nursing students: knowledge of the native language
      promotes integration].

PMID- 10948924
TI  - [From the field of endoscopy: standards facilitate cooperation].

PMID- 10948925
TI  - [The health insurance service reviews patients' applications with eased
      requirements. "Abuses concerning patients" applications should be eliminated].

PMID- 10948926
TI  - [Industrial management in nursing: effective control--disciplinary or
      interdisciplinary?].

PMID- 10948927
TI  - [Integration of the functional independence measure assessment: the planning of
      the nursing process may be cheaper and better].

PMID- 10948928
TI  - [The image of nursing in the next century: predetermined activities constitute a
      breach of basic rights].

PMID- 10948930
TI  - [Ambulatory surgery: introduction of a day care center].

PMID- 10948929
TI  - [Nursing visits to patients with dementias--3. We shall manage this better
      together].

PMID- 10948931
TI  - [Laughter: as we laugh so we live].

PMID- 10948932
TI  - [Guide for the practical education of nursing students. Oldenburg Hospital
      Nursing School].

PMID- 10948933
TI  - [Focus groups as a methodological approach to nursing research].
AB  - The authors describe in this article the methodologic approach of focus groups
      based on the experience they have had. They define the method's guidelines,
      taking a look at the main points of meeting organization, the role of team
      coordination and the moments of work group.

PMID- 10948934
TI  - [Problems with the concept of health regarding patients' beliefs].
AB  - To expand the understanding of health, an analysis of definitions by Horta
      (1979), by the VIII National Health Conference (1986) and by the World Health
      Organization (1946) was done. Similar elements of what was defined by Foucault as
      "pastoral power" were identified. Through Canguilhen and Dejours health
      definitions some subsidies are presented to allow a better understanding of
      health as a person's own subject, giving alternatives that will make possible a
      rupture on the "pastoral power".

PMID- 10948935
TI  - [Power relationships in the universe of nursing teachers].
AB  - In this article we discuss the everyday re-elaborations made by the Nursing
      teachers about the power relations in which they are included. As a methodology
      we used interviews and observation of the Nursing teachers in action. We analyzed
      the data from the point of view of gender in a anglo-tendency and concluded that
      Nursing teachers, as a qualitative minority on the power relations in their work,
      make frequent re-elaborations about those power relations and use other matters
      of power to reach goals on their work relations.

PMID- 10948936
TI  - [Visitors' opinion on the system of patient visits in an intensive care unit].
AB  - The objective of this study is to identify whether the current system of visits
      schedule and patient's information at a Clinical and Surgical Intensive Care Unit
      (ICU) satisfy the patient's visitors. To do it, two hundred questionnaires were
      distributed, during a month, and one hundred and sixty returned. The results
      showed that 70% of the visitors are satisfied with the current schedule; 67% come
      in daily; 66% are satisfied with the time they have for visiting, 54% asked for
      access in out of the current schedule, 69% are satisfied with staff information
      about patients; 88% of the visitors are patient's relatives. The most frequent
      suggestion was to increase the visit time at this ICU.

PMID- 10948937
TI  - [The nursing process in the daily lives of nursing students and nurses].
AB  - The present study aims to be a contribution to the Nursing student and the
      nurse's daily use of the Nursing process; the investigation method used was
      qualitative, applying semi-structured research tools; the data obtained were
      confronted with theoretical references and were put together in themes. The
      results show that the Nursing students and the nurses recognize the true value of
      the Nursing process, although they are not so sure about its practical use, and
      for them the Nursing schools should have the responsibility of promoting
      discussions in order to establish the theoretical references that would support
      the Nursing process. In other words, the schools should define one or more
      Nursing Theories and/or Conceptual References and its following methodologic
      definitions to be used on teaching the Nursing process.

PMID- 10948938
TI  - [What do people know about and expect from nurses?].
AB  - The purpose of the present study was to learn about people's opinions on nurses'
      performance and on what do they expect from it. Authors interviewed patients and
      their families in Health Institutions and people walking in malls at the cities
      of Ribeirao Preto (125) and Bauru (125). The interviews were recorded,
      transcribed and analyzed. Results showed that the nurse is recognized as the one
      who is responsible for the care but there is still a representation of nurses as
      the doctor's helper. They refer to the nurse as someone courageous, important and
      on whom they depend on. They look for human care, dedication, respect,
      responsibility, understanding, affection and efficiency. They enable nurses' work
      and recognize the lack of better work conditions and fair wages.

PMID- 10948939
TI  - [Nursing research, an active process in nursing].
AB  - Nursing knowledge can be produced through academic, assistance and collaborative
      model. There are few Nursing services in Brazil that stimulate research
      production by clinical nurses. This study aims to analyze declarations of nurses
      about the process of conducting research on their work places, having as a
      framework the symbolic interactionism. The data was collected through interviews
      with eleven nurses. The analysis led to the process of researching with six
      phases: the situation; the perception; the interpretation; the act; the
      manipulation and the consumation. The authors concluded that nurses interact with
      themselves and others, defining and interpreting their situation, their own
      actions as well as the other's. Through defining and interpreting the situation,
      they build their actions directed or not to activities related to research
      according to the meaning given by them to this "social object".

PMID- 10948940
TI  - [Macrocampaigns: alternatives to health promotion].
AB  - To reflect about teaching and practicing nursing in public and collective health,
      helps to direct the teaching/learning nursing process to a health promotion
      alternative, involving nursing students of UFRGS with Lions Clubs, Health State
      Secretaries and, specially, with the population and the media, so that early
      detection of high blood pressure and diabetes and also health promotion could be
      focus on Macro-campaigns Project. The aim is to early detect high blood pressure,
      diabetes and to promote health, individually and collectively, in a short period
      of time, at places of major concentration of persons, using academic work power,
      clubs of service, participation of the population and the media. The method used
      on this investigation was of interviews, blood pressure measurement, blood sugar
      checking, and filling forms from spontaneous demand in shoppings malls and other
      sites, by two professors and 58 nursing students of UFRGS. The main aspects of
      the results are that 15% of the demand have high blood pressure and 9% have high
      level of blood sugar.

PMID- 10948941
TI  - [Sensitizing nurses towards personalized care while nursing HIV-positive and AIDS
      patients].
AB  - The paper describes the author's experience on guiding "health workshops" as a
      way to sensitize nurses that take care of HIV-positive and AIDS patients through
      the development of humanized attention to their customers, according to Jean
      Watson's Trans-personal Care Theory. To do so, as a starting point we used the
      professionals reasoning throughout their career to highlight the importance of
      this approach.

PMID- 10948942
TI  - [What we have to prevent: negligence in the health care of children and
      adolescents].
AB  - The intra-familiar violence affects many children and teenagers as an usual
      familiar experience. In a theoretic study done aiming to bring contributions to
      prevent violence, including negligence, some elements emerge as essential of
      leading to effective help: knowledge, understanding and consequent reflection
      about its influencing and causing factors. Doing so, our professional nursing
      experiences as care givers led us to choose the ecosystem reference in its
      biological, cultural and contextual dynamics as presented by Barudy (1997), since
      we recognize it as appropriate to the social-economic and cultural conditions of
      a majority of the Brazilian families.

PMID- 10948943
TI  - [The low-birthweight child: everyday care given within the family context].
AB  - The aim of this study was to know the care given to low birth weight newborns and
      the cultural context in which it occurs. The method used to gather information
      was participant observation and interviews of the mothers of these babies in the
      district they live in Porto Alegre. Through ethnographic analysis with the
      construction of cultural domains, according to Spradley, the study wishes to
      document the child care and the relations between the mothers and the
      professionals of health care institutions. The cultural findings point out that
      there is a need to discuss the practice of perinatal care, especially to low
      birth weight newborns and also include cultural aspects into this care.

PMID- 10948944
TI  - [The communication process in the care of patients during echocardiography].
AB  - The article reviews some aspects of the communication process, its basic
      concepts, how it is approached in the theories of the nurses, and proposes to
      make reflections on the communication in the context of the patient undergoing
      the stress-echo study. Our goal is to emphasize and to rescue some important
      aspects related to the communication in health allies area, which is practiced in
      a constant manner in the daily practices of the nurse. Finally, this paper wishes
      to emphasize the importance of the knowledge of this process, incorporating it to
      the practice.

PMID- 10948945
TI  - [Health survey: a brief reflexion on individual and public health].
AB  - This article is a brief literature review that aims to stimulate reflections
      about individual and collective health concepts, especially approaching some
      authors which indicate to new health interventions nowadays. It features
      procedural and historical health aspects with the perspective of new orientations
      to follow its dynamism and complexity. It also refers to recommendations of
      international events to promote health in the 21st century.

PMID- 10948946
TI  - [Interdisciplinary actions: perception of the participants of a promotional and
      health care program].
AB  - The authors analyze the perceptions that participants of a promotional and health
      care program have about the meaning, the professional profile, advantages and
      difficulties of the interdisciplinary work. In a qualitative approach, the data
      have been collected through semi-structured interviews with professionals and
      students of nursing, nutrition and psychology, categorized with the technique of
      content analysis. It was perceived that the subjects characterize their practice
      as an interdisciplinary interaction. However, they need to overcome
      institutional, epistemological, psychosocial, cultural and material obstacles, in
      order to develop a methodology for the interdisciplinary work in a more explicit
      and effective way.

PMID- 10948947
TI  - [The model of clinical assistance and possibilities of doing it in a different
      way].
AB  - Nursing, in a clinical assistential model, and the daily practices in an in
      patient psychiatric unit, are approached. It seems to have a discordance between
      the health system and clients problems. The nurses seem to plan actions that
      accomplish institutional goals instead of reaching out for clients' individual
      needs. In mental health, to include the client on planning his care is
      fundamental to reach therapeutical goals. Even in the actual model, there are
      initiatives incorporating these approaches, rescuing concepts that bring clients
      and workers closer. By recognizing the subjectivity of professionals and clients,
      we can understand that they are both singular, bringing up interdisciplinarity,
      and also a process of hierarchy happens, giving autonomy to the working teams and
      enlarging the space of work.

PMID- 10948948
TI  - [The work of nursing in the production of health care in a clinical model].
AB  - The subject of this research study is the technological and social organization
      of health work in hospital, considering the position of nursing practice within
      production of care. The aim is to analyze the work process at a University
      Hospital to apprehend the configuration of practices, knowledges, social
      relations and technologies that are operated by agents in intervention on the
      body of an ill person. Using a dialectical approach, empirical data were
      collected by direct observation of the work process in a medical in-patient unit
      and by semi-structured interviews with professionals. It was found that the
      production of care is developed based on collective work, that is structured by
      the division in parts and fragmentation of the actions of the different agents,
      in order to produce a diagnosis and therapy. The agents articulate their actions
      around the medical act which takes up a central position in the production of
      care. The importance of broadening the clinical model to contemplate the social
      and subjective dimension of the health/disease process is pointed out in a
      therapeutical project shared by different health care team professionals. It is
      proposed to change the work process associated with the construction of new
      management models in health care institutions.

PMID- 10948949
TI  - [Public health work and nursing: concepts of the managers of Porto Alegre health
      units].
AB  - This is a descriptive study done in a qualitative perspective. It aims to
      describe the conceptions of health care units' managers about the work in public
      health. The subjects perceptions are that this work goes from interdisciplinary
      thought with a preventive focus to the curative practice of ambulatory care. On
      what concerns Nursing, nurses' management functions and auxiliaries assistance
      activities are pointed out. They believe that strategies to approximate to the
      SUS principles are necessary in the context of Public Health.

PMID- 10948951
TI  - [From normative power to human development--the search for upkeep of health].
AB  - This paper pretends to introduce a reflection about the notion of sustainable
      development in planning and generating practices and technologies concerned to
      health and, particularly, nursing. It questions the current model of development
      and its implications in health concepts and practices in a perspective of living
      quality.

PMID- 10948950
TI  - [Connecting care models and trends in health education: grants for nursing
      education].
AB  - In this article the authors establish a connection between health care models and
      pedagogical trends considering their education and health care experiences in the
      hospital and in the communities and also the review of the literature. The
      pedagogical trends and health care models used by nurses in nursing education
      demonstrate their world view. Therefore it is important that they understand what
      is behind their practice so that nursing is in a political and historical context
      and its practice can foster the social transformation or keep the status quo. The
      purpose of this study is to contribute to the construction of nursing education.

PMID- 10948952
TI  - [Use of participating observation and semi-structured interviews in nursing
      research].
AB  - An experience report of the researchers in the development of a qualitative
      research is presented. The limits and the possibilities found in the realization
      of the field work are described, while adopting participant observation and semi
      structured interview as techniques for data collection. The importance of the
      involvement level of the researcher with the subjects and some aspects that may
      interfere in the results to be achieved are emphasized.

PMID- 10948953
TI  - [I am 16 years old, have two children ... one day I will get married in a little
      green dress].
AB  - This study presents family relationships of teenage mothers in their daily
      experiences of motherhood. The attentive view of the author enlightens the
      comprehension of issues related to women, of life experiences characterized by
      discrimination involving class and gender issues.

PMID- 10948954
TI  - [The social sector and its contradictory relation to suffering].

PMID- 10948955
TI  - [Some aspects of psychosocial medicine].

PMID- 10948956
TI  - ["Suffering and precariousness", a multisectorial network].

PMID- 10948957
TI  - [Case history of Mr. J., an example within a network].

PMID- 10948958
TI  - [Risks and illusions in a partnership in mental health].

PMID- 10948959
TI  - [Taking care of psychotic patients alienated in a hospital environment].

PMID- 10948960
TI  - [What is the role of a specialized nurse in a general hospital?].

PMID- 10948961
TI  - ["I misunderstood..."].

PMID- 10948962
TI  - [Which central venous access for which patient?].

PMID- 10948963
TI  - [Insertion and removal of an implanted catheter].

PMID- 10948964
TI  - [Choice of needles and tubes].

PMID- 10948965
TI  - [Prevention of infections associated with the use of catheters].

PMID- 10948966
TI  - [Infoperf, all in the interest of the patient].

PMID- 10948967
TI  - [Nursing care of the implantation site].

PMID- 10948968
TI  - [Complications at the implantation site].

PMID- 10948969
TI  - [Taking steps for quality improvement].

PMID- 10948970
TI  - [Viewpoint of a male nurse on home nursing].

PMID- 10948971
TI  - Do innocent victims threaten the belief in a just world? Evidence from a modified
      Stroop task.
AB  - Two experiments tested whether innocent victims threaten observers' belief in a
      just world. In both experiments, participants viewed an innocent victim then
      performed a modified Stroop task in which they identified the color of several
      words presented for brief exposures (followed by a mask) on a computer screen.
      When the threat to justice beliefs was presumably highest, color-identification
      latencies were greater for justice-related words than for neutral words. In
      Experiment 2, under conditions of high threat, justice-related interference
      predicted participants' tendency to disassociate themselves from and derogate the
      victim. These findings suggest that innocent victims do threaten justice beliefs
      and responses to these victims may, at times, be attempts to reduce this threat.
      The methodology presented here may be applied to future investigations of
      defensive, counternormative processes reflecting people's concern with justice.

PMID- 10948972
TI  - Cultural styles, relational schemas, and prejudice against out-groups.
AB  - Two studies provide evidence that Latins (i.e., Mexicans and Mexican Americans)
      are guided by a concern with socioemotional aspects of workplace relations to a
      far greater degree than are Anglo-Americans. The focus on socioemotional
      considerations results in Latins having a relatively greater preference for
      workgroups having a strong interpersonal orientation. Preferred relational style
      had a far greater impact on preferences for workgroups and judgments about their
      likely success than did the ethnic composition of the workgroups for both Latins
      and Anglo-Americans. Evidence that the two groups differ markedly in relational
      schemas comes from examination of suggestions about how group performance could
      be improved, judgments about whether a focus on socioemotional concerns
      necessarily entails a reduction in task focus, and recall for socioemotional
      aspects of workgroup interactions. Implications for the dynamics of intercultural
      contact are discussed.

PMID- 10948973
TI  - Expression after suppression: a motivational explanation of postsuppressional
      rebound.
AB  - Five studies examined the effect of expressing a construct after suppressing it
      on subsequent accessibility. Suppression of color terms (Studies 1, 2, and 5) and
      of stereotypes (Studies 3 and 4) were examined. Both expression alone and
      suppression alone enhanced the construct's accessibility relative to the no
      suppression/no-expression condition, demonstrating activation by recent construct
      use and postsuppressional rebound, respectively. However, introducing expression
      after suppression reduced accessibility relative to both the suppression alone
      and the expression alone conditions. These results are explained within a
      motivational theory of rebound, according to which suppressing a construct
      induces a need to use it, and subsequent expression satisfies this need, thereby
      instigating an inhibition of the accessibility of need-related constructs.

PMID- 10948974
TI  - Cross-cultural differences in tolerance for crowding: fact or fiction?
AB  - It is widely believed that cultures vary in their tolerance for crowding. There
      is, however, little evidence to substantiate this belief, coupled with serious
      shortcomings in the extant literature. Tolerance for crowding has been confused
      with cultural differences in personal space preferences along with perceived
      crowding. Furthermore, the few studies that have examined cultural variability in
      reactions to crowding have compared subgroup correlations, which is not
      equivalent to a statistical interaction. Although the authors found a statistical
      interaction indicating that Asian Americans and Latin Americans differ in the way
      they perceive crowding in comparison to their fellow Anglo-American and African
      American citizens, all four ethnic groups suffer similar, negative psychological
      distress sequelae of high-density housing. These results hold independently of
      household income.

PMID- 10948975
TI  - "Mood contagion": the automatic transfer of mood between persons.
AB  - The current studies aimed to find out whether a nonintentional form of mood
      contagion exists and which mechanisms can account for it. In these experiments
      participants who expected to be tested for text comprehension listened to an
      affectively neutral speech that was spoken in a slightly sad or happy voice. The
      authors found that (a) the emotional expression induced a congruent mood state in
      the listeners, (b) inferential accounts to emotional sharing were not easily
      reconciled with the findings, (c) different affective experiences emerged from
      intentional and nonintentional forms of emotional sharing, and (d) findings
      suggest that a perception-behavior link (T. L. Chartrand & J. A. Bargh, 1999) can
      account for these findings, because participants who were required to repeat the
      philosophical speech spontaneously imitated the target person's vocal expression
      of emotion.

PMID- 10948976
TI  - Competence in early adult romantic relationships: a developmental perspective on
      family influences.
AB  - The present prospective, longitudinal study of 193 young adults (85 men, 108
      women, M = 20.7 years old) and their partners in ongoing romantic relationships
      in 1997 was initiated in 1989, when the 193 target youths were in the 7th grade.
      On the basis of the model for the development of early adult romantic
      relationships (DEARR; C. Bryant & R. D. Conger, in press), the authors
      hypothesized that interactional processes in the family of origin would predict
      interpersonal skills by the target youths, which would be positively related to
      the early adult couple's relationship quality. Observational ratings showed that
      nurturant-involved parenting in the family of origin predicted behaviors by the
      target youth to a romantic partner that were warm, supportive, and low in
      hostility. These competent behaviors of the target youth were positively
      associated with relationship quality for the early adult couple and also mediated
      or explained the connection between parenting and relationship quality.

PMID- 10948977
TI  - Should we create a niche or fall in line? Identity negotiation and small group
      effectiveness.
AB  - A prospective study of 423 MBA students examined the interplay of identity
      negotiation and group functioning. The findings revealed that self-verification
      effects (through which group members brought others to see them as they saw
      themselves) heightened participants' feelings of connection to their groups
      (i.e., more identification and social integration and less emotional conflict)
      and improved group project grades on creative tasks (tasks that benefit from
      divergent perspectives). Appraisal effects (through which groups brought members
      to see themselves as the group saw them) facilitated group project grades on
      computational tasks (tasks that require deriving one correct answer). In
      addition, self-verification effects were more prevalent than appraisal effects.
      The authors discuss the implications of these findings for understanding the
      links among self-verification, self-categorization, and group outcomes.

PMID- 10948978
TI  - Two personalities, one relationship: both partners' personality traits shape the
      quality of their relationship.
AB  - This research tested 6 models of the independent and interactive effects of
      stable personality traits on each partner's reports of relationship satisfaction
      and quality. Both members of 360 couples (N = 720) completed the Multidimensional
      Personality Questionnaire and were interviewed about their relationship. Findings
      show that a woman's relationship happiness is predicted by her partner's low
      Negative Emotionality, high Positive Emotionality, and high Constraint, whereas a
      man's relationship happiness is predicted only by his partner's low Negative
      Emotionality. Findings also show evidence of additive but not interactive
      effects: Each partner's personality contributed independently to relationship
      outcomes but not in a synergistic way. These results are discussed in relation to
      models that seek to integrate research on individual differences in personality
      traits with research on interpersonal processes in intimate relationships.

PMID- 10948979
TI  - Exploring individual differences in reactions to mortality salience: does
      attachment style regulate terror management mechanisms?
AB  - Five studies examined the contribution of attachment style to mortality salience
      effects. In Study 1, mortality salience led to more severe judgments of
      transgressions only among anxious-ambivalent and avoidant persons but not among
      secure persons. In addition, whereas anxious-ambivalent persons showed immediate
      and delayed increases in severity judgments, avoidant persons showed this
      response only after a delay period. In Study 2, anxious-ambivalent persons showed
      immediate and delayed increases in death-thought accessibility after death
      reminders. Avoidant and secure persons showed this effect only after a delay
      period. Study 3 revealed that worldview defense in response to mortality salience
      reduced death-thought accessibility only among avoidant persons. Studies 4-5
      revealed that mortality salience led to an increase in the sense of symbolic
      immortality as well as in the desire of intimacy only among secure persons, but
      not among avoidant and anxious-ambivalent persons.

PMID- 10948980
TI  - Mothers' personality and its interaction with child temperament as predictors of
      parenting behavior.
AB  - In this longitudinal, multimethod investigation, the authors examined mothers'
      personality and its interaction with infants' negative emotionality as predictors
      of parenting behavior. When infants were 8-10 months old (N = 112), mothers
      completed personality self-reports, and the authors observed infants' negative
      emotionality in both standard procedures and naturalistic daily contexts. When
      infants were 13-15 months old (N = 108), the authors observed two aspects of
      parenting, power assertion and maternal responsiveness, in mother-child
      interactive contexts. Maternal personality alone and also in interaction with
      child emotionality predicted future parenting behaviors. The longitudinal links
      established between personality and parenting behaviors indicate the predictive
      utility of personality. Findings also highlight the bidirectionality of the early
      parent-child relationship.

PMID- 10948981
TI  - Reexamining the circumplex model of affect.
AB  - The circumplex model of affect has been among the most widely studied
      representations of affect. Despite the considerable evidence cited in support of
      it, methods typically used to evaluate the model have substantial limitations. In
      this article, the authors attempt to correct past limitations by using a
      covariance structure model specifically designed to assess circumplex structure.
      This model was fit to 47 individual correlation matrices from published data
      sets. Analyses revealed that model fit was typically acceptable and that opposing
      affective states usually demonstrated strong negative correlations with one
      another. However, analyses also indicated substantial variability in both model
      fit and correlations among opposing affective states and suggested several
      characteristics of studies that partially accounted for this variability.
      Detailed examination of the locations of affective states for 10 of the
      correlation matrices with relatively optimal characteristics provided mixed
      support for the model.

PMID- 10948982
TI  - Cross-protection and reassortment studies with avian H2 influenza viruses.
AB  - In order to assess the degree of immune cross-protection among avian H2 influenza
      virus strains, mice were immunised with beta-propiolactone-inactivated virus
      preparations and infected intranasally with mouse-adapted variant of A/Black
      Duck/New Jersey/1580/78 (H2N3) strain. The experiments with 11 avian H2 strains
      revealed that both Eurasian and American H2 avian influenza viruses exhibit
      either high or moderate degree of cross-protection. The grouping of the strains
      in accordance with their cross-protection efficiency does not coincide with H2
      phylogenetic branches. Several reassortant clones were obtained with the use of
      A/Pintail Duck/Primorie/695/76 (H2N3) strain and high-yield X-67 reassortant as
      parent viruses, among them a high-yield H2N3 reassortant. Taking into account the
      data on cross-protection among avian H2 strains, the high-yield H2N3 reassortant
      may be regarded as a prototype strain to be used for the preparation of killed
      vaccines in the case of a new appearance of avian H2 haemagglutinin in
      circulation in humans.

PMID- 10948983
TI  - The genome structure of kyuri green mottle mosaic tobamovirus and its comparison
      with that of cucumber green mottle mosaic tobamovirus.
AB  - The genome of the Y strain of kyuri green mottle mosaic virus (KGMMV-Y) has been
      completely sequenced. Its genomic structure and sequence show it to be a typical
      tobamovirus, that is closest to, but distinct from, that of cucumber green mottle
      mosaic tobamovirus (CGMMV). The genomic sequence of KGMMV-Y was compared in
      detail with that of the SH strain of CGMMV. The sequences of their 5'- and 3'
      untranslated regions were 74% and 63% identical. The amino acid sequences of the
      shorter and longer (read through) RNA replicase components, movement protein (MP)
      and coat protein (CP) were 58, 58. 60 and 46% identical, respectively. The KGMMV
      Y genome sequence was also compared partly to that of another strain of KGMMV,
      KGMMV-C. The CP sequences of KGMMV-Y and KGMMV-C differed by 20 amino acid
      residues, suggesting that their relationship is more distant than the
      relationship between CGMMV-SH and CGMMV-W whose CP sequences are identical. The
      MPs of KGMMV-Y and KGMMV-C, however, differ only by one amino acid residue,
      although three amino acid substitutions are present in the MPs between CGMMV-SH
      and CGMMV-W. Two long stretches, one in the RNA replicase and the other in the
      MP, were highly conserved in KGMMV and CGMMV.

PMID- 10948984
TI  - Hepatocytes of double-transgenic mice expressing high levels of hepatitis B virus
      e antigen and interferon-gamma are not injured by HBeAg specific autoantibodies.
AB  - Seroconversion from HBeAg to alphaHBe of persons chronically infected by HBV is
      usually associated with a transient exacerbation of liver disease and subsequent
      normalization of liver histology. It is speculated that these clinico
      pathological features may be due to the activation of cytodestructive mechanisms
      by alphaHBe antibodies. The aim of the present study was to investigate the
      pathogenic potential of alphaHBe antibodies in a transgenic mouse model.
      Therefore, alphaHBe autoantibodies were elicited in double-transgenic mice
      expressing high amounts of HBeAg and interferon-gamma in the liver. Interferon
      gamma has reviously been shown to play an important role in the development of
      hepatic necroinflammation associated with hepadnaviral infection, probably via
      tumor-necrosis-factor-alpha secreted by activated macrophages. We found no
      evidence that alphaHBe antibodies have the potential to destroy HBeAg-secreting
      hepatocytes even if the cells were predisposed to injury due to high-level
      interferon-gamma expression. We conclude that seroconversion from HBeAg to
      alphaHBe of persons chronically infected with HBV seems to be an immunological
      epiphenomenon without pathogenic significance.

PMID- 10948985
TI  - Preliminary characterization of protein binding factor for porcine reproductive
      and respiratory syndrome virus on the surface of permissive and non-permissive
      cells.
AB  - In its natural host, porcine reproductive and respiratory syndrome virus (PRRSV)
      has been reported to have a restricted tropism for cells of the
      monocyte/macrophage lineage. To date, cloned monkey kidney cell lines, such as
      MARC-145 and CL2621 cells which have been established from MA-104 cells, are the
      only non-porcine cells known to support PRRSV replication. In the present study,
      a binding assay was set up to follow by flow cytometry the attachment of PRRSV on
      the surface of porcine and non-porcine cells. PRRSV was found to be able to bind
      permissive cells like porcine alveolar macrophages and MARC-145. Further binding
      assays with porcine peripheral blood leukocytes showed that only monocytes can
      attach the virus. By their lack of binding factor, lymphocytes appeared to be
      refractory to PRRSV infection. Pre-incubation of MARC-145 cells with chymotrypsin
      and pronase E, but not neuraminidase, blocked their binding activity for PRRSV.
      The binding activity of the protease-treated cells was regenerated 8 hours after
      treatment, but cells remained unable to bind PRRSV if maintained in the presence
      of cycloheximide, thus confirming the proteinic nature of the specific binding
      factor(s). Experiments conduced with cells that have been previously
      characterized as non-permissive to PRRSV infection showed that many of them were
      able to bind the virus. Data obtained suggest that interaction of PRRSV with a
      specific binding factor on the surface of some cells is not sufficient to lead to
      a productive infection, and that a second putative receptor or other phenomena
      are probably required to pursue later events.

PMID- 10948986
TI  - Human immunodeficiency virus reverse transcriptase base misincorporations can
      promote strand transfer.
AB  - A system to determine if HIV-reverse transcriptase (RT) base misincorporations
      can promote strand transfer was constructed. A donor RNA, on which RT-directed
      DNA synthesis was initiated, shared homology over a 119 base internal region with
      an acceptor RNA, to which DNAs initiated on the donor could transfer. Products
      completed on the donor in the presence or absence of acceptor were isolated and
      PCR was used to amplify these DNAs. PCR products were ligated into a vector which
      had this same region (near the N-terminus of the alpha-lac gene) removed.
      Transformed E. coli were screened in an alpha-complementation assay by blue-white
      phenotype analysis with white colonies scored as those with errors in plasmid
      derived alpha-lac. The frequence of white colonies +/- standard deviations was
      0.031 +/- 0.006 and 0.0037 +/- 0.009, for plasmids with inserts derived from
      donor-directed products synthesized with 100 microM dNTPs in the presence and
      absence of acceptor template, respectively. Statistical analysis indicated a
      lower white colony frequency in the presence of acceptor (p = 0.0025). The lower
      frequency with acceptor implies that a portion of the errors made on the donor
      are transferred to the acceptor suggesting that base misincorporations can induce
      strand transfer.

PMID- 10948987
TI  - Molecular characterization and pathogenesis of transmissible gastroenteritis
      coronavirus (TGEV) and porcine respiratory coronavirus (PRCV) field isolates co
      circulating in a swine herd.
AB  - TGEV replicates in intestinal enterocytes and causes diarrhea in young pigs.
      PRCV, a spike (S) gene deletion mutant of TGEV with an altered respiratory tissue
      tropism, causes mild or subclinical respiratory infections. Comparisons of TGEV
      and PRCV strains suggest that tropism and pathogenicity are influenced by the S
      gene and ORF3, respectively. Recently, outbreaks of TGE of reduced virulence were
      reported in the field. We investigated a similar suspect TGEV outbreak of reduced
      virulence in nursery pigs from a swine herd in the Midwest. A TGEV strain
      (BW021898B) was isolated in swine testicular cells from gut contents of a
      diarrheic pig and three PRCV strains (BW126, BW154, BW155) were isolated from
      nasal swabs from normal TGEV-seronegative sentinel pigs in contact with the
      diarrheic pigs. Sequence analysis of the TGEV isolate in the partial S gene and
      ORF3/3a and ORF3-1/3b revealed high homology with enteropathogenic TGEV strains.
      Gnotobiotic pig inoculation and histopathological results revealed that this TGEV
      isolate retained virulence even though in the field outbreak the diarrheal
      disease was of reduced severity. Sequence analysis of the S gene deletion region
      of the three PRCV isolates revealed identical deletions between nt 105-752, which
      differ from deletions previously reported among PRCV strains. The three PRCV
      isolates had variable sequence changes in ORF 3/3a and ORF 3-1/3b, affecting the
      ORF size and amino acid sequence. Thus, sequence analysis and pathogenicity
      studies indicate that this TGEV isolate resembles other enteropathogenic TGEV
      strains. Therefore, the reduced severity of TGE observed in this herd may be due
      to the ongoing PRCV infections, which induce antibodies cross-reactive with TGEV
      and result in decreased disease severity. The results outlined in this study
      highlight the need to monitor the molecular epidemiology of TGEV/PRCV strains
      with sensitive differential diagnostic assays, followed by sequence analysis of
      the critical regions to identify changes and pathogenicity studies to confirm the
      disease potential of the TGEV isolates.

PMID- 10948988
TI  - Mutations in the genome of porcine reproductive and respiratory syndrome virus
      responsible for the attenuation phenotype.

PMID- 10948989
TI  - Phylogenetic analysis of the S7 gene does not segregate Chinese strains of
      bluetongue virus into a single topotype.
AB  - Bluetongue virus (BTV) infection of ruminants is endemic throughout tropical and
      subtropical regions of the world. The S7 gene segments of prototype Chinese
      strains of BTV serotypes 1, 2, 3, 4, 12, 15, and 16 were sequenced and compared
      to the same genes of prototype strains of BTV from the US, Australia, and South
      Africa. The S7 genes and predicted VP7 proteins of the Chinese viruses were
      relatively conserved, with the notable exception of serotype 15. Furthermore,
      phylogenetic analysis of the S7 genes did not predict geographic origin of the
      various strains of BTV.

PMID- 10948990
TI  - Structure and variability of the 3' end of RNA 3 of Beet soil-borne pomovirus--a
      virus with uncertain pathogenic effects.
AB  - PCR products representing c. 550 3' terminal bases of Beet soil-borne pomovirus
      (BSBV) RNA 3 were compared for sources of this virus from all major sugarbeet
      growing areas in Germany. In none of these areas conspicious symptoms could be
      attributed to the presence of BSBV. Single strand conformation polymorphism
      analyses suggested that the BSBV genome may be very variable. This was confirmed
      by nucleotide sequence analysis. Each PCR product which was analysed showed
      sequence differences to others. Even the PCR products obtained from plants grown
      in the same soil sample were different. The highly variable nature of the BSBV
      genome is in contrast to the much more conserved nature of the Beet necrotic
      yellow vein virus genome. By means of the STAR programme a secondary structure
      was predicted for the 3' end of BSBV RNA 3, in which some areas are highly
      conserved, whereas others are characterized by a clustering of nucleotide
      exchanges.

PMID- 10948991
TI  - Genetic diversity of rice tungro spherical virus in tungro-endemic provinces of
      the Philippines and Indonesia.
AB  - The two adjacent genes of coat protein 1 and 2 of rice tungro spherical virus
      (RTSV) were amplified from total RNA extracts of serologically indistinguishable
      field isolates from the Philippines and Indonesia, using reverse transcriptase
      polymerase chain reaction (RT-PCR). Digestion with HindIII and BstYI restriction
      endonucleases differentiated the amplified DNA products into eight distinct coat
      protein genotypes. These genotypes were then used as indicators of virus
      diversity in the field. Inter- and intra-site diversities were determined over
      three cropping seasons. At each of the sites surveyed, one or two main genotypes
      prevailed together with other related minor or mixed genotypes that did not
      replace the main genotype over the sampling time. The cluster of genotypes found
      at the Philippines sites was significantly different from the one at the
      Indonesia sites, suggesting geographic isolation for virus populations.
      Phylogenetic studies based on the nucleotide sequences of 38 selected isolates
      confirm the spatial distribution of RTSV virus populations but show that gene
      flow may occur between populations. Under the present conditions, rice varieties
      do not seem to exert selective pressure on the virus populations. Based on the
      selective constraints in the coat protein amino acid sequences and the virus
      genetic composition per site, a negative selection model followed by random
      sampling events due to vector transmissions is proposed to explain the inter-site
      diversity observed.

PMID- 10948993
TI  - Recombinant expression and modification analysis of protein agno-1b encoded by
      avian polyomavirus BFDV.
AB  - Among two pairs of agnoproteins encoded in upstream positions in the late mRNAs
      of avian polyomavirus BFDV, either agno-1a or its splice derivative agno-1b are
      required for viral propagation. Out of the two proteins both of which consist of
      multiple electrophoretic subspecies, the smaller and less complex agno-1b has
      been cDNA-cloned into an influenza-virus /RNA-polymerase I expression system for
      production of higher amounts of this protein in infected chicken embryo
      fibroblasts. Fractional modification of agno-1b by phosphorylation at residues
      serine 51, serine 53, and threonine 73 is demonstrated through dephosphorylation
      by alkaline phosphatase, mass spectrometry of individual protein species isolated
      by strong anion exchange chromatography, and single or multiple alanine
      substitutions of serine or threonine residues in site-directed mutagenesis.

PMID- 10948992
TI  - Antigenic and genetic characterization of the fusion (F) protein of mumps virus
      strains.
AB  - Twelve strains of mumps virus, belonging to the A, C and D genotypes of the small
      hydrophobic (SH) protein gene, were investigated by nucleotide sequencing of the
      fusion protein gene. The nucleotide sequences and deduced amino acid sequences
      were aligned and compared with previously reported sequences of the gene. In
      addition an antigenic comparison between the F protein of different strains of
      the A, C and D genotypes was performed with ten monoclonal antibodies directed
      against the F protein of genotype A. Phylogenetic analysis of the coding region
      of the F gene showed the expected clustering of the different genotypes, as
      previously determined from the SH protein gene. Comparison of the 538 long amino
      acid sequence of the protein showed that only a small number of amino acids
      differed between the viral strains. The A genotype differed from B, C and D
      whereas the latter showed fewer consistent amino acid differences between
      themselves. Nine of the ten monoclonal antibodies reacted with the C and D
      genotypes and one failed to react with these genotypes. It is concluded that the
      structure and antigenicity of the F protein is well conserved both intra- and
      intergenotypically over long periods of time.

PMID- 10948994
TI  - A conserved leucine in the cytoplasmic domain of the Semliki Forest virus spike
      protein is important for budding.
AB  - Budding of alphaviruses at the plasma membrane has been shown to depend on
      specific amino acids of the spike protein and hydrophobic cavities of the
      nucleocapsid. Here the function of leucine401 in the cytoplasmic tail of the
      Semliki Forest virus spike protein was studied. When alanine and threonine were
      substituted for leucine the budding efficiency decreased. When the alanine mutant
      virus was passaged and sequenced a valine residue at position 401 was found which
      could partially restore budding proficiency. These results show that leucine401
      together with the previously identified tyrosine399 form a motif that is required
      for budding.

PMID- 10948995
TI  - Rinderpest virus infection in primary bovine skin fibroblasts.
AB  - Rinderpest virus (RPV) replicated to a high titre in primary bovine skin
      fibroblasts. The course of infection was similar to that seen in established cell
      lines. Virulent field virus grew at a faster rate than the fully attenuated
      vaccine strain of the virus. Virus antigen expression, as measured by FACScan
      analysis, correlated with the time course of infection for the two strains in
      cell cultures. Wild type virus, obtained directly from cattle, infected cells at
      a slower rate than virus passaged even once in primary bovine skin fibroblasts.
      This is the first report of a productive infection of primary bovine skin
      fibroblasts by wild type RPV.

PMID- 10948996
TI  - Specific detection of avian pneumovirus (APV) US isolates by RT-PCR.
AB  - This report details the development of an RT-PCR assay for the specific detection
      of US isolates of avian pneumovirus (APV). Of the several primer pairs tested,
      two sets of primers derived from the matrix gene of APV were able to specifically
      detect the viral RNA of APV. The nucleotide sequence comparison of the PCR
      products of APV isolates from Minnesota suggested that these viruses were closely
      related to the Colorado strain of APV, but were distinct from subtypes A and B
      European isolates of turkey APV (turkey rhinotracheitis: TRT). This M gene-based
      PCR was found to be very specific and sensitive. APV as low as 8 x 10(-5) TCID50
      (0.0323 microg/ml) could be detected using this assay. In addition, the two
      primers were able to differentiate isolates from turkeys in Minnesota.

PMID- 10948997
TI  - A new papillomavirus of possums (Trichosurus vulpecula) associated with typical
      wart-like papillomas.
AB  - A previously unknown, cutaneous papillomavirus (Papovaviridae) in a brushtail
      possum (Trichosurus vulpecula) was demonstrated. This represents one of the first
      viruses reported in this species. Possum papillomas were identified by typical
      wart-like appearance and histology. Papillomavirus particles were detected by
      electron microscopy in tissue homogenates following purification and negative
      staining. The polymerase chain reaction amplified a conserved portion of the L1
      gene which was purified and sequenced. Comparison of the DNA and deduced amino
      acid sequence from the possum papillomavirus with other papillomavirus sequences,
      together with phylogenetic analysis, indicated that this was a new
      papillomavirus.

PMID- 10948998
TI  - The major immediate-early genes of human cytomegalovirus induce two novel
      proteins with molecular weights of 91 and 102 kilodaltons.
AB  - Mouse monoclonal antibody MAB810 is known to recognize the major immediate-early
      (IE) proteins, 68 kDa IE1 (IE1p68) and 80 kDa IE2 (IE2p80), of human
      cytomegalovirus (HCMV). Using this antibody we found that two additional proteins
      with higher molecular weights of approximately 91 (p91) and 102 kDa (p102) are
      also synthesized in HCMV-infected cells. p91 and p102 were produced in cells
      stably transfected with plasmid expressing IE1p68 and IE2p80, respectively, and
      shown to be related with IE1p68 and IE2p80, respectively, in primary amino acid
      sequence. Taken together, these results indicate that p91 and p102 are expressed
      from the IE1 and IE2 genes, respectively.

PMID- 10948999
TI  - Influence of work rate incremental rate on the exercise responses in patients
      with COPD.
AB  - PURPOSE: The peak work rate (Wpeak) measured during a progressive stepwise
      exercise test is commonly used to select the target training intensity for an
      exercise training program. In healthy subjects, a greater Wpeak is achieved when
      a faster rate of increase in work rate is used, whereas VO2 peak is independent
      of the rate of increase in work rate. This effect might be even more pronounced
      in chronic obstructive pulmonary disease (COPD) patients, in whom the VO2
      kinetics during exercise are slower compared with healthy subjects. METHODS: To
      investigate this, we studied 10 COPD patients (9 M/1 F, age: 65+/-5 yr [mean +/-
      SD], FEV1: 33+/-8%). They underwent, on separate days, three stepwise exercise
      tests on an ergocycle. For each test, increments of 5, 10, or 20 W x min(-1) were
      used in random order; the investigator was blinded as to which increment was
      used. VO2, VCO2, heart rate (HR), minute ventilation (VE), breathlessness and leg
      fatigue at rest, at each work rate, and at maximal capacity were obtained.
      RESULTS: Wpeak averaged 40+/-13, 53+/-14, and 66+/-19 W for the 5-, 10-, and 20-W
      protocol, respectively (P < 0.001), whereas VO2 peak was comparable at 0.96+/
      0.16, 1.02+/-0.18, and 1.03+/-0.20 L x min(-1). As the rate of increase in work
      rate became faster, the VO2/work rate relationship shifted to the right. This is
      exemplified by the VO2 at 40 W, which averaged 0.98+/-0.06, 0.90+/-0.09, and
      0.83+/-0.10 L x min(-1) for the 5-, 10-, and 20-W protocol, respectively (P <
      0.05). Similar observations were made for the relationship between HR, VE, and
      symptom scores, and work rate. There was no significant differences in peak
      values for HR and VE, and symptoms scores. CONCLUSIONS: We conclude that the work
      rate incremental rate influences the Wpeak achieved, whereas the peak values for
      VO2, HR, VE, and symptom scores remain comparable. These findings have practical
      implications for the exercise evaluation of patients with COPD.

PMID- 10949000
TI  - Overuse injuries in the elite rock climber.
AB  - Closed rupture of the flexor tendon sheath has been known to occur in the elite
      rock climbing population. However, only one study has investigated the prevalence
      of this entity. PURPOSE: To examine an elite climbing group in this country for
      the prevalence of pulley rupture and report on other commonly occurring injuries
      in the hand and elbow. METHODS: 42 elite rock climbers competing at the U.S.
      national championships were evaluated by an injury survey and concentrated
      examination of the hand and elbow. Manual testing for clinical bowstringing was
      done for each finger, by the same examiner. RESULTS: 11 subjects (26%) had
      evidence of flexor pulley rupture or attenuation, as manifested by clinical
      bowstringing. Injury to the PIP collateral ligament had occurred in 17 subjects
      (40%). Other commonly occurring injury syndromes are described. CONCLUSION: Our
      results and others suggest that closed traumatic pulley rupture occurs with
      significant frequency in this population. In addition, all subjects with this
      injury continued to climb at a high standard and reported no functional
      disability.

PMID- 10949001
TI  - Total and regional bone density in male runners, cyclists, and controls.
AB  - PURPOSE: Male athletes who were runners (N = 12), cyclists (N = 14), or both (N =
      13) were compared with nonexercising age-matched controls (N = 23) for total and
      regional bone mineral density (BMD). All athletic subjects had competed for a
      minimum of 3 yr and trained for a minimum of 4 h x wk(-1). Runners undertook no
      cycling and cyclists undertook no running training. METHODS: All subjects were
      scanned for whole body and L1-L4 spine BMD using a Hologic QDR 1000W scanner
      (Hologic Inc., Bedford, MA). RESULTS: There were no differences in age, height,
      weight, body mass index (BMI), % fat, or hours of training between any of the
      athletic groups (P > 0.05), although compared with controls, runners and cyclists
      had lower body mass index (P < 0.01) and all athletic groups had lower % fat (P <
      0.001). Compared with controls, runners had greater total and leg BMD (P < 0.05),
      cyclists had reduced spine BMD (P = 0.05), and athletes of the "both" group had
      greater total (P < 0.05) and arm BMD (P < 0.01). CONCLUSION: Running is
      associated with increased bone density, particularly in the leg, whereas cycling
      is associated with a mild decrease in bone density in the spine. In athletes who
      do both, running exerts a stronger influence than cycling.

PMID- 10949002
TI  - Epidemiology of women's recreational ice hockey injuries.
AB  - INTRODUCTION: Participation in ice hockey by women is increasing in many parts of
      North America; however, research into injuries and the patterns of injury among
      female players associated with this activity is limited. PURPOSE: The purpose of
      this research was to examine the incidence and nature of injuries suffered by
      female recreational ice hockey players. METHODS: This prospective study followed
      314 female players from 33 teams in Edmonton, Canada, during the 1997-1998 hockey
      season. Injury and game attendance data were collected using monthly telephone
      interviews throughout the season. Diagnostic information for individuals who
      received medical treatment was solicited from the attending health professional.
      RESULTS: A total of 102 players reported a total of 125 injuries for a rate 7.5
      injuries/1000 player exposures. The anatomic region most often injured was the
      lower extremity (31.2%), and the most common diagnosis was sprain/strain (52.0%).
      The predominant injury mechanism was player contact, either as a result of
      collision with another player or a body check (40.0%). Of all injuries, 65.6%
      occurred during league games, 27.2% during play-off, tournament, or exhibition
      games, and 7.2% during practices. Although less than 1% of injuries resulted in
      hospitalization, 17.6% of injuries resulted in an absence from hockey of 8 or
      more days. CONCLUSION: The diagnostic and anatomic distribution of injury in the
      women's hockey league was similar to that in leagues where full facial protection
      is mandatory. The observed injury rate was lower than the rates reported for male
      recreational and collegiate ice hockey players. Female recreational ice hockey
      players are at risk for injuries and further research is required to identify
      areas for injury prevention.

PMID- 10949003
TI  - Influence of carbohydrate on cytokine and phagocytic responses to 2 h of rowing.
AB  - PURPOSE: This study examined the influence of carbohydrate (C) versus placebo (P)
      beverage ingestion on the phagocytic and cytokine responses to normal rowing
      training by 15 elite female rowers. METHODS: Athletes received C or P before,
      during and after, two, 2-h bouts of rowing performed on consecutive days. Blood
      was collected before and 5-10 min and 1.5 h after rowing. Metabolic measures
      indicated that training was performed at moderate intensities, with some high
      intensity intervals interspersed throughout the sessions. RESULTS: Concentrations
      of blood neutrophils and monocytes, phagocytic activity, and plasma IL-1ra were
      significantly lower postexercise after C versus P ingestion. No differences were
      observed for oxidative burst activity, IL-6, IL-8, or TNFalpha. Glucose was
      significantly higher after 2 h of rowing with C ingestion; however, cortisol,
      growth hormone, epinephrine, norepinephrine, and CRP were not affected by
      carbohydrate. CONCLUSIONS: These data indicate that carbohydrate compared with
      placebo ingestion attenuated the moderate rise in blood neutrophils, monocytes,
      phagocytosis, and plasma IL-1ra concentrations that followed 2-h bouts of
      training in elite female rowers. No changes in blood hormone concentrations were
      found.

PMID- 10949004
TI  - Response to stimulation-evoked eccentric muscle contractions in hypertensive
      rats.
AB  - PURPOSE: The purpose of this study was to determine whether the functional
      deficits observed in the skeletal muscles of adult, spontaneously hypertensive
      rats (SHR) arise because of an inability of injured muscles to regenerate
      normally in the hypertensive environment. METHODS: Force decline and recovery
      were evaluated in SHR tibialis anterior (TA) at various times after a series of
      192 eccentric contractions (EC). EC were produced by supramaximal electrical
      stimulation of the sciatic nerve in anesthetized rats. Experiments compared TA
      muscles in 3- and 6-month-old SHR with TA in age-matched, normotensive Wistar
      Kyoto rats (WKY) after one or three exposures to the EC protocol. The repeat
      exposures were separated by 10 d. RESULTS: TA in SHR and WKY rats experienced a
      similar decline in strength and a similar level of recovery after one or three
      exposures to 192 EC. TA in both strains showed a similar 10-15% increase in dry
      weight and cross-sectional area after three exposures to the EC protocol.
      Contractile strength increased by 16-28% in WKY TA after three exposures to EC,
      but the increase was limited to 7% in 3-month SHR TA and was not evident in 6
      month SHR TA, despite the 15% increase in muscle mass. CONCLUSIONS: The data
      indicate that muscle mass and strength can increase in response to electrically
      evoked EC and that an increase in strength can be significantly greater than an
      increase in mass after the first few exposures to EC in normotensive animals.
      Maintained hypertension does not increase the loss of contractile strength after
      vigorous EC but limits or prevents the EC-induced increase in muscle strength
      that accompanies repeated exposure to the protocol.

PMID- 10949005
TI  - Exercise training improves left ventricular isovolumic relaxation.
AB  - PURPOSE: Left ventricular (LV) diastolic function is an important determinant of
      aerobic fitness. The purpose of this paper was to investigate the relationship
      between aerobic fitness and the rate and extent of isovolumic LV relaxation.
      METHODS: Two series of experiments were performed utilizing both human and animal
      models. In the first series of experiments, the relationship between LV diastolic
      time intervals and exercise capacity was assessed in two groups of collegiate men
      (N = 18) with variable peak run times (Bruce protocol). In the second series of
      experiments, the extent of LV relaxation was examined in sedentary and exercise
      trained rats (treadmill running), using an isolated, isovolumic heart
      preparation. Subsequent morphological assessment was also performed in rats.
      RESULTS: At rest, men with greater peak treadmill time had a shorter resting LV
      isovolumic relaxation time (R-R interval adjusted 1000 ms) (long duration
      runners, 84+/-5 ms vs short duration runners, 105+/-7 ms, P < 0.05) despite a
      similar LV diastolic interval. Peak treadmill time was inversely correlated to LV
      isovolumic relaxation time (R-R interval adjusted 1000 ms) (r = -0.55; P < 0.02).
      In animal studies (N = 26), the LV pressure-volume relationship was shifted
      rightward in exercise-trained rats (P = 0.003). Exercise-trained rats had an
      increased LV inner diameter (sedentary, 5.1+/-0.35 mm vs exercise-trained, 6.1+/
      0.28 mm, P < 0.05) and a thicker interventricular septum (sedentary, 1.52+/-0.06
      mm vs exercise-trained, 1.72+/-0.09 mm, P < 0.05). CONCLUSION: This study
      suggests that both the rate and extent of LV isovolumic relaxation is enhanced
      with exercise training. Further study is required to understand the
      interrelationship between exercise and diastolic function.

PMID- 10949007
TI  - Macronutrient intake and whole body protein metabolism following resistance
      exercise.
AB  - The provision of carbohydrate (CHO) supplements following resistance exercise
      attenuated muscle protein (PRO) degradation (Roy et al. J. Appl. Physiol. 82:1882
      1888, 1997). The addition of PRO may have a synergistic effect upon whole body
      protein balance by increasing synthesis (Biolo et al. Am. J. Physiol. 273:E122
      E129, 1997). PURPOSE: To determine if the macronutrient composition of a
      postexercise beverage would alter muscle anabolism and/or catabolism following
      resistance exercise. METHODS: We provided isoenergetic CHO (1 g x kg(-1)) and
      CHO/PRO/FAT supplements and placebo (PL) immediately (t = 0 h) and 1 h (t = + 1
      h) following resistance exercise (9 exercises/3 sets/80% 1 RM) to 10 young,
      healthy, resistance-trained males. Whole body leucine turnover was determined
      from L-[1-13C]leucine kinetics at approximately 4 h postexercise. RESULTS: No
      differences were observed for urinary 3-methylhistidine or urea nitrogen
      excretion between the trials. Leucine flux was significantly elevated at
      approximately 4 h postexercise for both CHO/PRO/FAT (177.59+/-12.68 micromol x
      kg(-1) x h(-1)) and CHO (156.18+/-7.77 micromol x kg(-1) x h(-1)) versus PL
      (126.32+/-10.51 micromol x kg(-1) x h(-1)) (P < 0.01). Whole body leucine
      oxidation was elevated at approximately 4 h for CHO/PRO/FAT (29.50+/-3.34
      micromol x kg(-1) h(-1)) versus CHO (16.32+/-2.33 micromol x kg(-1) x h(-1)) (P <
      0.01) and PL (21.29+/-2.54 micromol x kg(-1) x h(-1)) (P < 0.05). Nonoxidative
      leucine disposal (NOLD) was significantly elevated at approximately 4 h for both
      CHO/PRO/FAT (148.09+/-10.37 micromol x kg(-1) x h(-1)) and CHO (139.86+/-7.02
      micromol x kg(-1) x h(-1)) versus PL (105.03+/-8.97 micromol x kg(-1) x h(-1)) (P
      < 0.01). CONCLUSIONS: These results suggest that consumption of either CHO or
      CHO/PRO/FAT immediately and 1 h following a resistance training bout increased
      NOLD as compared with a placebo.

PMID- 10949006
TI  - Effect of respiratory muscle training on GLUT-4 in the sheep diaphragm.
AB  - PURPOSE: Endurance exercise training is associated with enhanced glucose uptake
      and hence improvement in carbohydrate metabolism. Glucose transport (GLUT)
      membrane proteins are regulated by a variety of physiological stimuli, including
      exercise. In limb muscle, both acute exercise and endurance training enhance the
      expression of the skeletal muscle transporter, GLUT-4. The purpose of this study
      is to determine whether chronic loading enhances GLUT-4 expression in the
      diaphragm. METHODS: The effect of chronic inspiratory flow resistive (IFR)
      loading on diaphragm GLUT-4 was studied in a model of respiratory muscle
      endurance training in sheep. IFR loads (resistance 50-100 cm H2O x L(-1) x s(-1))
      were maintained for 3 h x d(-1), 5-6 d x wk(-1) for 3 wk. Loading was adjusted so
      that PaO2 was >60 Torr and PaCO2 <45 Torr in room air. Six untrained sheep were
      used as controls. GLUT-4 protein and mRNA were analyzed by Western and Northern
      analysis respectively. RESULTS: GLUT-4 protein levels were two-fold greater in
      trained animals when compared with controls (P < 0.01). GLUT-4 mRNA levels in the
      trained muscles was not significantly different from controls. CONCLUSIONS: We
      conclude that in the sheep diaphragm, chronic IFR loading increases GLUT-4
      protein levels. This increase may be one of the mechanisms contributing to the
      improved respiratory muscle endurance previously demonstrated in this animal
      model of respiratory muscle training.

PMID- 10949008
TI  - Differential baroreflex control of heart rate in sedentary and aerobically fit
      individuals.
AB  - PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity
      in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x
      min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy
      young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were
      assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus
      injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively.
      Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of
      both pressure and suction delivered to the carotid sinus via a neck chamber
      collar, independent of drug administration. RESULTS: During vasoactive drug
      injection, mean arterial pressure (MAP) was similarly altered in average fit (AF)
      and high fit (HF) groups. However, the heart rate (HR) response range of the
      arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x
      min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained
      neck suction and pressure were applied to counteract altered carotid sinus
      pressure during SN and PE administration, isolating the ABR response, the
      response range remained diminished (P < 0.05) in the HF population (24+/-3 beats
      x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR
      perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1))
      response ranges were similar. The arterial baroreflex response range was
      significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x
      min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS:
      These data confirm that reductions in arterial-cardiac reflex sensitivity are
      mediated by diminished ABR function. More importantly, these data suggest that
      the integrative relationship between the ABR and CBR contributing to arterial
      baroreflex control of HR is inhibitory in nature and not altered by exercise
      training.

PMID- 10949009
TI  - Validation of the Minnesota Leisure Time Physical Activity Questionnaire In
      Spanish Women. Investigators of the MARATDON Group.
AB  - PURPOSE: Regular physical activity (PA) is associated with lower risk for several
      chronic diseases. It is important to validate PA measurement instruments in
      different populations. The objective was to validate the Minnesota leisure time
      PA questionnaire among Spanish women. METHODS: A cross-sectional study with quota
      sampling was designed. Two PA groups (active, expending less than 301 MET-min x
      d(-1) in PA, and very active, expending more than 300 MET-min x d(-1)) and two
      age groups (18-40 and 41-60 yr) were defined. The Minnesota questionnaire was
      administered to obtain total energy expenditure in leisure time PA (EEPAtotal)
      and classified according to the intensity of the different types of PA
      (EEPAheavy, EEPAmoderate, and EEPAlight). The 250 women recruited performed an
      exercise test to assess fitness. RESULTS: Spearman correlation coefficients among
      EEPAtotal, EEPAheavy, EEPAmoderate, EEPAlight, and fitness were 0.39, 0.51, 0.13,
      and 0.02, respectively. Multiple linear regression model adjusted by the
      different EEPAs and age accounted for 46% of fitness variability. Besides age,
      only EEPAmoderate and EEPAheavy were associated with fitness. CONCLUSION: The
      Spanish version of the Minnesota questionnaire is a valid instrument for
      measuring leisure time PA performed in the last year in Spanish women aged 18-60
      yr. Moderate and heavy physical activity are adequately assessed whereas light
      physical activity practice assessment may be questionable.

PMID- 10949010
TI  - Familiality of triglyceride and LPL response to exercise training: the HERITAGE
      study.
AB  - PURPOSE: The main purpose of the present investigation was to test whether and to
      what extent familial/genetic factors are involved in the changes of postheparin
      lipoprotein lipase (deltaPH-LPL) activity and triglyceride (deltaTG) levels in
      response to exercise training. Additional hypotheses were also tested as to
      whether there were familial/genetic factors shared by baseline and the
      corresponding response to exercise training (i.e., by baseline triglyceride
      (TG(B)) and deltaTG and by baseline postheparin lipoprotein lipase (PH-LPL(B))
      and deltaPH-LPL activity). METHODS: Serum TG and PH-LPL were measured in 459
      subjects from 99 sedentary Caucasian families of the HERITAGE Family study before
      (baseline) and after completing a 20 wk (3 times per week) exercise training
      protocol. The training protocol had a target intensity of 75% of the heart rate
      associated with baseline VO2max during the last 6 wk. PH-LPL activity was
      measured in the study subjects. Both univariate and bivariate familial
      correlation analyses were applied to the baseline and response data. RESULTS: The
      maximal heritabilities for deltaTG and deltaPH-LPL activity were 22% and 15%,
      respectively. There were no common familial factors for TG(B) and deltaTG, nor
      were there any for PH-LPL(B) and deltaPH-LPL. However, we found that there were
      common familial factors underlying deltaTG and deltaPH-LPL; these familial
      factors seemed to differ across sex and generation groups. CONCLUSION: Although
      there were no common familial factors underlying the covariation between the
      baseline triglyceride and PH-LPL activity and the corresponding responses to
      exercise training (i.e., TG(B) with deltaTG or PH-LPL(B) with deltaPH-LPL), the
      deltaTG and deltaPH-LPL covariation apparently share some common familial
      determinants.

PMID- 10949011
TI  - Longitudinal changes in physical activity in a biracial cohort during
      adolescence.
AB  - PURPOSE: This report describes the development and use of two self-report methods
      and an objective measure to assess longitudinal changes in physical activity in a
      large biethnic cohort of young girls from childhood through adolescence. METHODS:
      The NHLBI Growth and Health Study (NGHS) is a multicenter study of obesity
      development in 2379 black and white girls followed from ages 9-10 yr to 18-19 yr
      (NGHS years 1-10). A Caltrac activity monitor was used to objectively quantify
      activity levels in years 3-5. A 3-d diary (AD) and a habitual patterns
      questionnaire (HAQ) were administered annually and biannually, respectively, to
      subjectively quantify physical activity levels. The changing pattern of
      activities as the girls matured during the 10-yr study period necessitated
      periodic form changes. Empirical analytic approaches were developed to help
      distinguish between true longitudinal changes in activity levels from potential
      numerical artifacts resulting from modifications in forms. RESULTS: The
      longitudinal activity data indicate a steep decline in the level of reported
      activity from baseline to year 10 as indicated by AD scores (446.8 to 292.1 MET
      min x d(-1), 35%) as well as by HAQ scores (29.3 to 4.9 MET-times x wk(-1), 83%).
      This parallel trend in the pattern of the decline in activity among the two self
      report methods was mirrored by a similar decline using the Caltrac method of
      physical activity assessment. From years 3 to 5, the AD decreased by 22%, whereas
      both the HAQ and Caltrac declined by 21%. CONCLUSION: The longitudinal data on
      physical activity collected in the NGHS cohort further confirm a dramatic
      decrease in the overall level of physical activity during the transition from
      childhood to adolescence. The consistency among the three methods indicate that
      both the AD and HAQ are useful tools for the assessment of activity levels in
      adolescent girls.

PMID- 10949012
TI  - Tracking of activity and fitness and the relationship with cardiovascular disease
      risk factors.
AB  - PURPOSE: To analyze tracking of daily physical activity and physical fitness
      (both cardiopulmonary [VO2max] and neuromotor fitness) and the longitudinal
      relationship with biological risk factors for cardiovascular disease (CVD), i.e.,
      total serum cholesterol (TC), high-density lipoprotein (HDL), the TC:HDL ratio,
      systolic and diastolic blood pressure, and the sum of four skinfolds. METHODS:
      Data were obtained from the Amsterdam Growth and Health Study; an observational
      longitudinal study with six repeated measurements over a period from 13 to 27 yr
      of age (N = 181). The statistical analyses were carried out with generalized
      estimating equations. RESULTS: Low to moderate tracking (both stability and
      predictability of early measurements) was observed for daily physical activity
      and VO2max, whereas good tracking was observed for neuromotor fitness. Daily
      physical activity was positively related to HDL (P < 0.01), and inversely to the
      TC:HDL ratio (P < 0.05) and to the sum of four skinfolds (P < 0.01). VO2max was
      also inversely related to the TC:HDL ratio (P < 0.01) and to the sum of four
      skinfolds (P < 0.01). In addition, VOmax was also inversely related to TC (P <
      0.01). Neuromotor fitness was inversely related to the sum of four skinfolds (P <
      0.01), and positively to systolic blood pressure (P < 0.01). CONCLUSIONS: The
      longitudinal development of physical activity and VO2max were related to a
      healthy CVD risk profile. For the development of neuromotor fitness, the picture
      was less clear. The relationships among physical activity, physical fitness, and
      lipoproteins and blood pressure were highly influenced by body fatness.

PMID- 10949013
TI  - Measuring physical strain during ambulation with accelerometry.
AB  - PURPOSE: To study the feasibility of ambulatory accelerometry in the evaluation
      of physical strain in walking at different speeds and different levels of
      economy. METHODS: Twelve able-bodied subjects performed a walking test on a
      treadmill with increasing walking speed. After a 6-wk period, these measurements
      were repeated, with an additional test of perturbed walking. Motility (the
      intensity of body segment movements, measured with accelerometry), heart rate,
      and oxygen uptake were simultaneously recorded. Feasibility was determined by
      comparing motility with percentage heart rate reserve (%HRR), using oxygen uptake
      (VO2) as reference. The relation with oxygen uptake, the sensitivity to change
      when walking speed increased and gait was perturbed, and intrasubject and
      intersubject variability were studied. RESULTS: Walking with increasing walking
      speed resulted in a higher pooled r2 value (0.91) and a lower residual standard
      deviation (1.44 mL x kg(-1) x min(-1)) for the motility-VO2 relation than for the
      %HRR-VO2 relation (0.84 and 1.92 mL x kg(-1) x min(-1), respectively).
      Furthermore, the motility-VO2 relation for this part of the protocol showed
      lowest interindividual differences. The sensitivity to changes due to an increase
      in walking speed, and the test-retest reliability were the highest for motility.
      Walking with a brace resulted in a lower pooled r2 value for the motility-VO2
      relation than for the %HRR-VO2 relation (0.31 and 0.67, respectively); the
      sensitivity to changes due to walking with a brace was lower for motility than
      for %HRR. CONCLUSION: Compared with heart rate, accelerometry allows accurate
      measurement with little error in any able-bodied individual, without the need for
      individual calibration. The response of motility to changes and differences in
      economy in patients requires further study.

PMID- 10949014
TI  - Knee strength deficits after hamstring tendon and patellar tendon anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to examine the strength of the knee
      flexors and knee extensors after two surgical techniques of ACL reconstruction
      and compare them to an age and activity level matched control group. METHODS:
      Twenty-four subjects who had undergone ACL reconstruction greater than 1 yr
      previously were placed into one of two groups according to autograft donor site:
      patellar tendon (BPB; N = 8) and hamstring (H; N = 16), and compared with an
      active, control group (N = 30). Knee flexor and extensor strength was evaluated
      using isovelocity dynamometry (5 speeds, eccentric and concentric, 5-95 degrees
      ROM). Strength maps were used to graphically analyze strength over a broad
      operational domain of the neuromuscular system. Average strength maps were
      determined for each autograft group and compared with controls. A difference map
      (control minus graft group) and confidence (t-test) maps were used to
      quantitatively identify strength deficits. RESULTS: The combined ACL group (N =
      24) revealed a global 25.5% extensor strength deficit, with eccentric regional
      (angle and velocity matched) deficits up to 50% of control. Strength deficits
      covered over 86% of the sampled strength map area (P < 0.01). These knee extensor
      strength deficits are greater than previously reported. In addition, the BPB
      group demonstrated a concentric, low velocity, knee extensor strength deficit at
      60-95 degrees that was not observed in the H group. Significant graft site
      dependent, regional knee flexor deficits of up to 50% of control were observed
      for the H group. CONCLUSIONS: Strength deficits localized to specific contraction
      types and ranges of motion were demonstrated between the ACL and control groups
      that were dependent upon autograft donor site. Postoperative rehabilitation
      protocols specific to these deficits should be devised.

PMID- 10949015
TI  - Short-term overtraining: effects on performance, circulatory responses, and heart
      rate variability.
AB  - PURPOSE AND METHODS: Nine elite canoeists were investigated concerning changes in
      performance, heart rate variability (HRV), and blood-chemical parameters over a 6
      d training camp. The training regimen consisted of cross-country skiing and
      strength training, in total 13.0+/-1.6 h, corresponding to a 50% increase in
      training load. RESULTS: Time to exhaustion (RunT) decreased from 19.1+/-1.0 to
      18.0+/-1.2 min (P < 0.05). VO2max and max lactate (La(max)) both decreased
      significantly (P < 0.05) over the training period (4.99+/-0.97 to 4.74+/-0.98 L x
      min(-1) and from 10.08+/-1.25 to 8.98+/-1.03 mmol x L(-1) respectively). Heart
      rates (HR) decreased significantly at all workloads. Plasma volume increased by
      7+/-7% (P < 0.05). Resting cortisol, decreased from 677+/-244 to 492+/-222 nmol x
      L(-1) (P < 0.05), whereas resting levels of adrenaline and noradrenaline remained
      unchanged. The change between tests in RunT correlated significantly with the
      change in HRmax (r = 0.79; P = 0.01). There were no group changes in high or low
      frequency HRV, neither at rest nor following a tilt. CONCLUSIONS: The reduced
      maximal performance indicates a state of fatigue/overreaching and peripheral
      factors are suggested to limit performance even though HRmax and La(max) both
      were reduced. The reduced submaximal heart rates are probably a result of
      increased plasma volume. HRV in this group didn't seem to be affected by short
      term overtraining.

PMID- 10949016
TI  - Peak power predicts performance power during an outdoor 16.1-km cycling time
      trial.
AB  - PURPOSE: To assess i) the reproducibility of peak power output recorded during a
      maximal aerobic power test (MAP), and ii) its validity to predict endurance
      performance during a field based 16.1-km time trial (16.1-km TT). METHODS: Two
      studies were completed: for part I, nine subjects performed three MAP tests; for
      part II, 16 subjects completed a MAP test and 16.1-km TT. Power output was
      recorded using an SRM power meter and was calculated as peak power output (PPO)
      recorded during 60 s of MAP and mean power output for the 16.1-km TT (16.1-km
      TT(PO)). RESULTS: There was no difference between PPO recorded during the three
      MAP trials, mean coefficient of variation for individual cyclists was 1.32%
      (95%CI = 0.97-2.03), and test-retest reliability expressed as an intraclass
      correlation coefficient was 0.99 (95%CI = 0.96-1.00). A highly significant
      relationship was found between PPO and 16.1-km TT(PO) (r = 0.99, P < 0.001) but
      not for PPO and 16.1-km TT time (r = 0.46. P > 0.05). CONCLUSION: The results
      show that PPO affords a valid and reliable measure of endurance performance which
      can be used to predict average power during a 16.1-km TT but not performance
      time.

PMID- 10949017
TI  - Oxygen uptake and ventilatory effects of an external nasal dilator during
      ergometry.
AB  - INTRODUCTION: Athletes and coaches have begun to use external nasal dilators with
      the perception that they enhance performance and make it "easier to breathe."
      This study was conducted to ascertain whether application of an external nasal
      dilator would enhance performance, as measured by maximal oxygen uptake (VO2max),
      maximal ventilation (V(Emax)), maximal work rate (Wr(max)) or ratings of
      perceived exertion and dyspnea (RPE, RPD). METHODS: Fifteen subjects (F = 10; M =
      5: age, 20+/-1.4, mean +/- SD) performed three incremental exercise tests to
      fatigue on an ergometer at 1-wk intervals in randomized order. One test was
      conducted without a nasal dilator, using a nose clip and mouthpiece for oxygen
      uptake and ventilatory measurements (control, C). The other two tests used a
      Rudolph 8900 breathing mask that included the nose in the breathing circuit and
      subjects wore either a placebo (P) or the active dilator (A). RPE for total body
      (20-point scale) and for dyspnea (10-point scale) were also measured on all
      tests. RESULTS: There were no significant differences in VO2max (mean +/- SD; C =
      3.12+/-1.1; P = 3.12 + 1.06; A = 3.04+/-0.94). V(Emax) (C = 117+/-26; P = 125+/
      31; A = 122+/-26), Wr(max) (C = 256+/-73; P = 255+/-70; A = 257+/-74), RPE (C =
      18.8+/-1.78; P = 18.9+/-1.33; A = 18.9+/-1.22), or RPD (C = 9.1+/-1.58; P = 9.3+/
      1.2; A = 9.13+/-1.2) during exercise between any group. CONCLUSION: Thus, it is
      concluded that an external nose dilator does not enhance performance as measured
      by VO2max, V(Emax), Wr(max), or perceived performance as measured by RPE and RPD.

PMID- 10949018
TI  - Maximal endurance time at VO2max.
AB  - INTRODUCTION: There has been significant recent interest in the minimal running
      velocity which elicits VO2max. There also exists a maximal velocity, beyond which
      the subject becomes exhausted before VO2max is reached. Between these limits,
      there must be some velocity that permits maximum endurance at VO2max, and this
      parameter has also been of recent interest. This study was undertaken to model
      the system and investigate these parameters. METHODS: We model the bioenergetic
      process based on a two-component (aerobic and anaerobic) energy system, a two
      component (fast and slow) oxygen uptake system, and a linear control system for
      maximal attainable velocity resulting from declining anaerobic reserves as
      exercise proceeds. Ten male subjects each undertook four trials in random order,
      running until exhaustion at velocities corresponding to 90, 100, 120, and 140% of
      the minimum velocity estimated as being required to elicit their individual
      VO2max. RESULTS: The model development produces a skewed curve for endurance time
      at VO2max, with a single maximum. This curve has been successfully fitted to
      endurance data collected from all 10 subjects (R2 = 0.821, P < 0.001). For this
      group of subjects, the maximal endurance time at VO2max can be achieved running
      at a pace corresponding to 88% of the minimal velocity, which elicits VO2max as
      measured in an incremental running test. Average maximal endurance at VO2max is
      predicted to be 603 s in a total endurance time of 1024 s at this velocity.
      CONCLUSION: Endurance time at VO2max can be realistically modeled by a curve,
      which permits estimation of several parameters of interest; such as the minimal
      running velocity sufficient to elicit VO2max, and that velocity for which
      endurance at VO2max is the longest.

PMID- 10949019
TI  - Age and gender responses to strength training and detraining.
AB  - PURPOSE: The purpose of this study was to examine the effects of age and gender
      on the strength response to strength training (ST) and detraining. METHODS:
      Eighteen young (20-30 yr) and 23 older (65-75 yr) men and women had their one
      repetition maximum (1 RM) and isokinetic strength measured before and after 9 wk
      of unilateral knee extension ST (3 d x wk(-1)) and 31 wk of detraining. RESULTS:
      The young subjects demonstrated a significantly greater (P < 0.05) increase in 1
      RM strength (34+/-3%; 73+/-5 vs 97+/-6 kg; P < 0.01) than the older subjects
      (28+/-3%; 60+/-4 vs 76+/-5 kg, P < 0.01). There were no significant differences
      in strength gains between men and women in either age group with 9 wk of ST or in
      strength losses with 31 wk of detraining. Young men and women experienced an 8+/
      2% decline in 1 RM strength after 31 wk of detraining (97+/-6 vs 89+/-6 kg, P <
      0.05). This decline was significantly less than the 14+/-2% decline in the older
      men and women (76+/-5 vs 65+/-4 kg, P < 0.05). This strength loss occurred
      primarily between 12 and 31 wk of detraining with a 6+/-2% and 13+/-2% decrease
      in the young and older subjects, respectively, during this period. DISCUSSION:
      These results demonstrate that changes in 1 RM strength in response to both ST
      and detraining are affected by age. However, ST-induced increases in muscular
      strength appear to be maintained equally well in young and older men and women
      during 12 wk of detraining and are maintained above baseline levels even after 31
      wk of detraining in young men, young women, and older men.

PMID- 10949020
TI  - Energy expenditure by heart rate in children: an evaluation of calibration
      techniques.
AB  - PURPOSE: To evaluate the impact of applying seven calibration equations (CE) in
      the estimation of free-living total energy expenditure (TEE) over 2-3 d in seven
      boys (mean +/- SD age 9.4+/-0.4 yr) by the Flex heart rate (HR) method. METHODS:
      HR and oxygen consumption were measured simultaneously for eight activities
      (lying, sitting, standing, arm-reaching exercise, a stooping-and-twisting
      exercise, stepping, treadmill walking/running, and cycle ergometry) carried out
      in sequence. CE were derived from various combinations of activities. Flex HRs
      were identified for each CE. RESULTS: There were no significant differences in
      TEE estimates [range (mean +/- SD); 6.65+/-0.72 to 7.27+/-0.89 MJ x d(-1)]
      derived from any of the CE. Mean daytime HR ranged from 86+/-4 to 122+/-15 beats
      x min(-1), and 82-98% of recorded daytime HR was < or = 140 beats x min(-1). As a
      result, within-subject CV in TEE from each of the CE ranged from 2.2% to 8.9%.
      Mean between-subject Flex HR ranged from 94+/-8 to 111+/-8 beats x min(-1). No
      significant differences were observed in corresponding TEE estimates. However,
      mean activity energy expenditure (AEE) ranged from 2.10+/-1.18 MJ x d(-1) (based
      on Flex HR 111+/-8 beats-min(-1)) to 3.55+/-1.44 MJ x d(-1) (based on Flex HR
      94+/-8 beats x min(-1); NS). The corresponding estimates of resting energy
      expenditure (REE) were 1.89+/-0.82 MJ x d(-1) (Flex HR 111+/-8 beats-min(-1)) and
      1.05+/-0.60 MJ x d(-1) (Flex HR 94+/-8 beats x min(-1)). Only the differences
      between the minimum and maximum estimates of REE were significant (P < 0.05).
      CONCLUSIONS: Unduly lengthy and complex calibration procedures for the estimation
      of Flex HR TEE may not be justified in most cases, particularly in sedentary
      children.

PMID- 10949021
TI  - Development of normative values for resting and exercise rate pressure product.
AB  - PURPOSE: The purpose of this study was to develop multivariate models to quantify
      resting, submaximal, and maximal rate pressure products (RPP). METHODS: A
      validation sample (N = 1623) was randomly selected from a clinically healthy
      population, and four cross-validation samples were randomly selected from a
      clinical cohort. The cross-validation samples were patients who had a negative
      exercise ECG with (Neg-Med, N = 179) and without cardiovascular drug (Neg-NoMed,
      N = 350), and patients who had a positive exercise ECG with (Pos-Med, N = 60) and
      without cardiovascular drug (Pos-NoMed, N = 75). Men made up 83% of the
      validation sample (mean age = 44.2+/-8.7) and women 17% (mean age = 39.7+/-10.1).
      The validation sample was used to develop multiple regression equations to
      quantify resting, submaximal, and maximal RPP. RESULTS: Results indicated that
      gender, body mass index (BMI), and physical activity level (Ex-code) were
      significantly related with resting RPP. Gender, age, BMI, and Ex-code were
      significantly related with maximal RPP. Gender, age, BMI, Ex-code, and percent of
      maximal heart rate at submaximal exercise (%HRmax) were significantly related
      with submaximal RPP. The multiple correlations for the resting, submaximal, and
      maximal models were 0.29 (SE = 16.75 beats x min(-1) x mm Hg), 0.87 (SE = 29.04
      beats x min(-1) x mm Hg), and 0.31 (SE = 42.41 beats x min(-1) x mm Hg),
      respectively. The accuracy of the models was confirmed when applied to the Neg
      NoMed and Pos-NoMed samples but not the Neg-Med and Pos-Med samples. This result
      suggest that the regression models developed from this study can be generalized
      to other populations where patients were not taking cardiovascular medication.
      Microcomputer programs were suggested to evaluate RPP at rest, maximal exercise,
      and submaximal exercise. CONCLUSION: Normative RPP for resting and exercise
      relies on multiple fitness parameters. Practical regression models are developed
      and can be applied to patients without cardiovascular medication.

PMID- 10949022
TI  - The Bub2p spindle checkpoint links nuclear migration with mitotic exit.
AB  - Bfa1p and Bub2p are spindle checkpoint proteins that likely have GTPase
      activation activity and are associated with the budding yeast spindle pole body
      (SPB). Here, we show that Bfa1p and Bub2p bind the Ras-like GTPase Tem1p, a
      component of the mitotic exit network, to the cytoplasmic face of the SPB that
      enters the bud, whereas the GDP/GTP exchange factor Lte1p is associated with the
      cortex of the bud. Migration of the SPB into the bud probably allows activation
      of Tem1p through Lte1p, thereby linking nuclear migration with mitotic exit.
      Since components of the Bub2p checkpoint are conserved in other organisms, we
      propose that the position of the SPB or mammalian centrosome controls the timing
      of mitotic exit.

PMID- 10949023
TI  - Junctophilins: a novel family of junctional membrane complex proteins.
AB  - Junctional complexes between the plasma membrane (PM) and
      endoplasmic/sarcoplasmic reticulum (ER/ SR) are a common feature of all excitable
      cell types and mediate cross-talk between cell surface and intracellular ion
      channels. We have identified the junctophilins (JPs), a novel conserved family of
      proteins that are components of the junctional complexes. JPs are composed of a
      carboxy-terminal hydrophobic segment spanning the ER/SR membrane and a remaining
      cytoplasmic domain that shows specific affinity for the PM. In mouse, there are
      at least three JP subtypes: JP-1, -2, and -3. JP-2 is abundantly expressed in the
      heart, and mutant mice lacking JP-2 exhibited embryonic lethality. Cardiac
      myocytes from the mutant mice showed deficiency of the junctional membrane
      complexes and abnormal Ca2+ transients. Our results suggest that JPs are
      important components of junctional membrane complexes.

PMID- 10949024
TI  - The level of C/EBP protein is critical for cell migration during Drosophila
      oogenesis and is tightly controlled by regulated degradation.
AB  - The C/EBP transcription factor, Slbo, is required for migration of border cells
      during Drosophila oogenesis. Unexpectedly, we find that neither increase nor
      decrease of Slbo activity is tolerated in border cells. Correct protein level is
      in part ensured by cell type-specific regulated turnover of Slbo protein. Through
      genetic screening, we identify two genes that are involved in this regulation.
      The Ubp64 ubiquitin hydrolase acts as a stabilizer of Slbo protein. A novel gene,
      tribbles, is a negative regulator of slbo in vivo. Tribbles acts by specifically
      targeting Slbo for rapid degradation via ubiquitination.

PMID- 10949025
TI  - Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1.
AB  - Bcl-x(L), an antiapoptotic Bcl-2 family member, is postulated to function at
      multiple stages in the cell death pathway. The possibility that Bcl-x(L) inhibits
      cell death at a late (postmitochondrial) step in the death pathway is supported
      by this report of a novel apoptosis inhibitor, Aven, which binds to both Bcl-x(L)
      and the caspase regulator, Apaf-1. Identified in a yeast two-hybrid screen, Aven
      is broadly expressed and is conserved in other mammalian species. Only those
      mutants of Bcl-x(L)that retain their antiapoptotic activity are capable of
      binding Aven. Aven interferes with the ability of Apaf-1 to self-associate,
      suggesting that Aven impairs Apaf-1-mediated activation of caspases. Consistent
      with this idea, Aven inhibited the proteolytic activation of caspases in a cell
      free extract and suppressed apoptosis induced by Apaf-1 plus caspase-9. Thus,
      Aven represents a new class of cell death regulator.

PMID- 10949026
TI  - 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain
      phosphorylation.
AB  - The Bcl-2 homology 3 (BH3) domain of prodeath Bcl-2 family members mediates their
      interaction with prosurvival Bcl-2 family members and promotes apoptosis. We
      report that survival factors trigger the phosphorylation of the proapoptotic Bcl
      2 family member BAD at a site (Ser-155) within the BAD BH3 domain. When BAD is
      bound to prosurvival Bcl-2 family members, BAD Ser-155 phosphorylation requires
      the prior phosphorylation of Ser-136, which recruits 14-3-3 proteins that then
      function to increase the accessibility of Ser-155 to survival-promoting kinases.
      Ser-155 phosphorylation disrupts the binding of BAD to prosurvival Bcl-2 proteins
      and thereby promotes cell survival. These findings define a mechanism by which
      survival signals inactivate a proapoptotic Bcl-2 family member, and suggest a
      role for 14-3-3 proteins as cofactors that regulate sequential protein
      phosphorylation events.

PMID- 10949027
TI  - TNF-alpha signals apoptosis through a bid-dependent conformational change in Bax
      that is inhibited by E1B 19K.
AB  - The adenovirus E1B 19K gene product is an inhibitor of apoptosis induced by tumor
      necrosis factor-alpha (TNF-alpha) during viral infection. We report that E1B 19K
      inhibited neither caspase-8 activation nor caspase-8-dependent Bid cleavage by
      TNF-alpha. Rather, TNF-alpha induced a tBid-dependent conformational change in
      Bax that allowed an interaction between E1B 19K and conformationally altered Bax,
      which caused inhibition of cytochrome c release and caspase-9 activation. E1B 19K
      expression interrupted caspase-3 processing, permitting cleavage to remove the
      p12 subunit but not the prodomain consistent with caspase-8 and not caspase-9
      enzymatic activity. Thus, E1B 19K blocks TNF-alpha-mediated death signaling by
      inhibiting a specific form of Bax that interrupts caspase activation downstream
      of caspase-8 and upstream of caspase-9.

PMID- 10949028
TI  - ARK-1 inhibits EGFR signaling in C. elegans.
AB  - A screen for synthetic enhancers of sli-1 identified ark-1 (forAck-related
      tyrosine kinase), a novel inhibitor of let-23 EGFR signaling in C. elegans. An
      ark-1 mutation synergizes with mutations in other negative regulators of let-23,
      resulting in increased RAS signaling. Genetic analysis suggests that ARK-1 acts
      upstream of RAS and is dependent upon SEM-5. ARK-1 inhibits LET-23-mediated
      ovulation, a RAS-independent function. ARK-1 physically interacts with SEM-5 in
      the yeast two-hybrid assay. We find that sem-5 also has a negative function in
      let-23-mediated ovulation and suggest that this negative function is mediated by
      the recruitment of inhibitors such as ARK-1.

PMID- 10949029
TI  - Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and
      sensitivity in livers of lipodystrophic and ob/ob mice.
AB  - In mice with too little fat (lipodystrophy) or too much fat (ob/ob), leptin
      deficiency leads to hyperglycemia, hyperinsulinemia, and insulin resistance. In
      both disorders, the liver overproduces glucose as a result of resistance to the
      normal action of insulin in repressing mRNAs for gluconeogenic enzymes. Here we
      show that chronic hyperinsulinemia downregulates the mRNA for IRS-2, an essential
      component of the insulin-signaling pathway in liver, thereby producing insulin
      resistance. Despite IRS-2 deficiency, insulin continues to stimulate production
      of SREBP-1c, a transcription factor that activates fatty acid synthesis. The
      combination of insulin resistance (inappropriate gluconeogenesis) and insulin
      sensitivity (elevated lipogenesis) establishes a vicious cycle that aggravates
      hyperinsulinemia and insulin resistance in lipodystrophic and ob/ob mice.

PMID- 10949030
TI  - Loss of insulin signaling in hepatocytes leads to severe insulin resistance and
      progressive hepatic dysfunction.
AB  - The liver plays a central role in the control of glucose homeostasis and is
      subject to complex regulation by substrates, insulin, and other hormones. To
      investigate the effect of the loss of direct insulin action in liver, we have
      used the Cre-loxP system to inactivate the insulin receptor gene in hepatocytes.
      Liver-specific insulin receptor knockout (LIRKO) mice exhibit dramatic insulin
      resistance, severe glucose intolerance, and a failure of insulin to suppress
      hepatic glucose production and to regulate hepatic gene expression. These
      alterations are paralleled by marked hyperinsulinemia due to a combination of
      increased insulin secretion and decreased insulin clearance. With aging, the
      LIRKO liver exhibits morphological and functional changes, and the metabolic
      phenotype becomes less severe. Thus, insulin signaling in liver is critical in
      regulating glucose homeostasis and maintaining normal hepatic function.

PMID- 10949031
TI  - Site-specific serine phosphorylation of the IL-3 receptor is required for
      hemopoietic cell survival.
AB  - In the hemopoietic compartment, IL-3, GM-CSF, and IL-5 receptors are major
      transducers of survival signals; however, the receptor-proximal events that
      determine this vital function have not been defined. We have found that IL-3
      stimulation induces phosphorylation of Ser-585 of beta(c). This promotes the
      association of phospho-Ser-585 of beta(c) with 14-3-3 and the p85 subunit of PI 3
      K. Mutation of Ser-585 specifically impairs the PI 3-K signaling pathway and
      reduces cell survival in response to IL-3. These results define a distinct IL-3
      receptor-mediated survival pathway regulated by site-specific receptor serine
      phosphorylation and 14-3-3 binding and suggest that this novel mode of signaling
      may be utilized by disparate transmembrane receptors that have as a common theme
      the transduction of survival signals.

PMID- 10949032
TI  - Essential role of p38alpha MAP kinase in placental but not embryonic
      cardiovascular development.
AB  - p38alpha MAP kinase is activated in response to many cellular stresses and also
      regulates the differentiation and/or survival of various cell types in vitro,
      including skeletal muscle cells and cardiomyocytes. Here we show that targeted
      inactivation of the mouse p38alpha gene results in embryonic lethality at
      midgestation correlating with a massive reduction of the myocardium and
      malformation of blood vessels in the head region. However, this defect appears to
      be secondary to insufficient oxygen and nutrient transfer across the placenta.
      When the placental defect was rescued, p38alpha(-/-) embryos developed to term
      and were normal in appearance. Our results indicate that p38alpha is required for
      placental organogenesis but is not essential for other aspects of mammalian
      embryonic development.

PMID- 10949033
TI  - Pathway specificity by the bifunctional receptor frizzled is determined by
      affinity for wingless.
AB  - The Frizzled (Fz) protein in Drosophila is a bifunctional receptor that acts
      through a GTPase pathway in planar polarity signaling and as a receptor for
      Wingless (Wg) using the canonical Wnt pathway. We found that the ligand-binding
      domain (CRD) of Fz has an approximately 10-fold lower affinity for Wg than the
      CRD of DFz2, a Wg receptor without polarity activity. When the Fz CRD is replaced
      by the high-affinity CRD of DFz2, the resulting chimeric protein gains Wg
      signaling activity, yet also retains polarity signaling activity. In contrast,
      the reciprocal exchange of the Fz CRD onto DFz2 is not sufficient to confer
      polarity activity to DFz2. This suggests that Fz has an intrinsic capacity for
      polarity signaling and that high-affinity interaction with Wg couples it to the
      Wnt pathway.

PMID- 10949034
TI  - Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand
      dependent interaction with TFIIH and participation of CDK7.
AB  - Phosphorylation of the estrogen receptor alpha (ERalpha) N-terminal transcription
      activation function AF1 at serine 118 (S118) modulates its activity. We show here
      that human ERalpha is phosphorylated by the TFIIH cyclin-dependent kinase in a
      ligand-dependent manner. Furthermore, the efficient phosphorylation of S118
      requires a ligand-regulated interaction of TFIIH with AF2, the activation
      function located in the ligand binding domain (LBD) of ERalpha. This interaction
      involves (1) the integrity of helix 12 of the LBD/AF2 and (2) p62 and XPD, two
      subunits of the core TFIIH. These findings are suggestive of a novel mechanism by
      which nuclear receptor activity can be regulated by ligand-dependent recruitment
      of modifying activities, such as kinases.

PMID- 10949035
TI  - Activation of human liver glycogen phosphorylase by alteration of the secondary
      structure and packing of the catalytic core.
AB  - Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1
      phosphate, which enters glycolysis to fulfill the energetic requirements of the
      organism. Maintaining control of blood glucose levels is critical in minimizing
      the debilitating effects of diabetes, making liver glycogen phosphorylase a
      potential therapeutic target. To support inhibitor design, we determined the
      crystal structures of the active and inactive forms of human liver glycogen
      phosphorylase a. During activation, forty residues of the catalytic site undergo
      order/disorder transitions, changes in secondary structure, or packing to
      reorganize the catalytic site for substrate binding and catalysis. Knowing the
      inactive and active conformations of the liver enzyme and how each differs from
      its counterpart in muscle phosphorylase provides the basis for designing
      inhibitors that bind preferentially to the inactive conformation of the liver
      isozyme.

PMID- 10949036
TI  - Crystal structure of the DNA binding domain of the replication initiation protein
      E1 from papillomavirus.
AB  - Papillomaviral infection causes both benign and malignant lesions and is a
      necessary cause of cervical carcinoma. Replication of this virus requires the
      replication initiation proteins E1 and E2, which bind cooperatively at the origin
      of replication (ori) as an (E1)2-(E2)2-DNA complex. This is a precursor to larger
      E1 complexes that distort and unwind the ori. We present the crystal structure of
      the E1 DNA binding domain refined to 1.9 A resolution. Residues critical for DNA
      binding are located on an extended loop and an alpha helix. We identify the E1
      dimerization surface by selective mutations at an E1/E1 interface observed in the
      crystal and propose a model for the (E1)2-DNA complex. These and other
      observations suggest how the E1 DNA binding domain orchestrates assembly of the
      hexameric helicase on the ori.

PMID- 10949037
TI  - Periodic conformational changes in rRNA: monitoring the dynamics of translating
      ribosomes.
AB  - In protein synthesis, a tRNA transits the ribosome via consecutive binding to the
      A (acceptor), P (peptidyl), and E (exit) site; these tRNA movements are catalyzed
      by elongation factor G (EF-G) and GTP. Site-specific Pb2+ cleavage was applied to
      trace tertiary alterations in tRNA and all rRNAs on pre- and posttranslocational
      ribosomes. The cleavage pattern of deacylated tRNA and AcPhe-tRNA changed
      individually upon binding to the ribosome; however, these different conformations
      were unaffected by translocation. On the other hand, translocation affects 23S
      rRNA structure. Significantly, the Pb2+ cleavage pattern near the peptidyl
      transferase center was different before and after translocation. This structural
      rearrangement emerged periodically during elongation, thus providing evidence for
      a dynamic and mobile role of 23S rRNA in translocation.

PMID- 10949038
TI  - Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein
      survivin.
AB  - The coupling of apoptosis (programmed cell death) to the cell division cycle is
      essential for homeostasis and genomic integrity. Here, we report the crystal
      structure of survivin, an inhibitor of apoptosis, which has been implicated in
      both control of cell death and regulation of cell division. In addition to a
      conserved N-terminal Zn finger baculovirus IAP repeat, survivin forms a dimer
      through a symmetric interaction with an intermolecularly bound Zn atom located
      along the molecular dyad axis. The interaction of the dimer-related C-terminal
      alpha helices forms an extended surface of approximately 70 A in length.
      Mutagenesis analysis revealed that survivin dimerization and an extended
      negatively charged surface surrounding Asp-71 are required to counteract
      apoptosis and preserve ploidy. These findings may provide a structural basis for
      a dual role of survivin in inhibition of apoptosis and regulation of cell
      division.

PMID- 10949039
TI  - Crystal structure of human survivin reveals a bow tie-shaped dimer with two
      unusual alpha-helical extensions.
AB  - Survivin is a mitotic spindle-associated protein involved in linking mitotic
      spindle function to activation of apoptosis in mammalian cells. The structure of
      the full-length human survivin has been determined by X-ray crystallography to
      2.7 A. Strikingly, the structure forms a very unusual bow tie-shaped dimer. It
      does not dimerize through a C-terminal coiled-coil, contrary to sequence analysis
      prediction. The C-terminal helices contain hydrophobic clusters with the
      potential for protein-protein interactions. The unusual shape and dimensions of
      survivin suggest it serves an adaptor function through its alpha-helical
      extensions.

PMID- 10949040
TI  - The yeast nuclear cap binding complex can interact with translation factor eIF4G
      and mediate translation initiation.
AB  - The mRNA cap structure is bound by either the nuclear (CBC) or the cytoplasmic
      (eIF4F) cap binding complex. Following mRNA export, CBC must be exchanged for
      eIF4F in the cytoplasm. It is not known how this exchange occurs or how this RNP
      remodeling event is integrated with mRNA function. Here we report genetic and
      biochemical evidence that the yeast translation initiation factor eIF4G
      associates with CBC, and that eIF4E, the eIF4F component that binds both the cap
      and eIF4G, antagonizes this interaction. Furthermore, we find that CBC can
      stimulate translation in extracts containing an eIF4G protein deficient for eIF4E
      binding. These data suggest that eIF4E binding to the eIF4G-CBC complex on newly
      exported mRNA displaces CBC, and that the first round of translation on mRNA may
      occur via a different mechanism than subsequent rounds.

PMID- 10949042
TI  - Drosophila segment borders result from unilateral repression of hedgehog activity
      by wingless signaling.
AB  - Body structures of Drosophila develop through transient developmental units,
      termed parasegments, with boundaries lying between the adjacent expression
      domains of wingless and engrailed. Parasegments are transformed into the
      morphologically distinct segments that remain fixed. Segment borders are
      established adjacent and posterior to each engrailed domain. They are marked by
      single rows of stripe expressing cells that develop into epidermal muscle
      attachment sites. We show that the positioning of these cells is achieved through
      repression of Hedgehog signal transduction by Wingless signaling at the
      parasegment boundary. The nuclear mediators of the two signaling pathways,
      Cubitus interruptus and Pangolin, function as activator and symmetry-breaking
      repressor of stripe expression, respectively.

PMID- 10949041
TI  - Mediator-nucleosome interaction.
AB  - Mediator, a multiprotein complex involved in the regulation of RNA polymerase II
      transcription, binds to nucleosomes and acetylates histones. Three lines of
      evidence identify the Nut1 subunit of Mediator as responsible for the histone
      acetyltransferase (HAT) activity. An "in-gel" HAT assay reveals a single band of
      the appropriate size. Sequence alignment shows significant similarity of Nut1 to
      the GCN5-related N-acetyltransferase superfamily. Finally, recombinant Nut1
      exhibits HAT activity in an in-gel assay.

PMID- 10949043
TI  - Characterization of follistatin isoforms in early Xenopus embryogenesis.
AB  - Follistatin is expressed in Spemann's organizer in the Xenopus gastrula and
      mimics the activity of the organizer, inducing a neural fate directly in the
      ectoderm. We have previously shown that follistatin inhibits BMP activity through
      a direct interaction. In this study, we have characterized the localization and
      function of two follistatin isoforms to examine the functional differences
      between them. One notable difference, previously described, is that the shorter
      form (xFSS or xFS319) but not the C-terminally extended long form (xFSL)
      associates with cell-surface matrices. Here, we show that the spatial-temporal
      expression pattern of xFSL and xFSS is indistinguishable. Interestingly, however,
      xFSS was found to have a more potent inhibitory activity against BMP-4 than xFSL.
      Furthermore, using a surface plasmon resonance biosensor, xFSS was shown to have
      a higher binding capacity for BMP subtypes. The diffusion rates of xFSS and xFSL
      ectopically expressed in Xenopus embryos were similar. Taken together, our
      results suggest that the difference in BMP-inhibiting activity of the two
      follistatin isoforms is mainly attributable to a difference in their BMP binding
      properties rather than to their diffusion rates.

PMID- 10949044
TI  - Characterization of two novel lipocalins expressed in the Drosophila embryonic
      nervous system.
AB  - We have found two novel lipocalins in the fruit fly Drosophila melanogaster that
      are homologous to the grasshopper Lazarillo, a singular lipocalin within this
      protein family which functions in axon guidance during nervous system
      development. Sequence analysis suggests that the two Drosophila proteins are
      secreted and possess peptide regions unique in the lipocalin family. The mRNAs of
      DNLaz (for Drosophila neural Lazarillo) and DGLaz (for Drosophila glial
      Lazarillo) are expressed with different temporal patterns during embryogenesis.
      They show low levels of larval expression and are highly expressed in pupa and
      adult flies. DNLaz mRNA is transcribed in a subset of neurons and neuronal
      precursors in the embryonic CNS. DGLaz mRNA is found in a subset of glial cells
      of the CNS: the longitudinal glia and the medial cell body glia. Both lipocalins
      are also expressed outside the nervous system in the developing gut, fat body and
      amnioserosa. The DNLaz protein is detected in a subset of axons in the developing
      CNS. Treatment with a secretion blocker enhances the antibody labeling,
      indicating the DNLaz secreted nature. These findings make the embryonic nervous
      system expression of lipocalins a feature more widespread than previously
      thought. We propose that DNLaz and DGLaz may have a role in axonal outgrowth and
      pathfinding, although other putative functions are also discussed.

PMID- 10949045
TI  - Evidence that the protein tyrosine phosphatase (PC12,Br7,Sl) gamma (-) isoform
      modulates chondrogenic patterning and growth.
AB  - One of the earliest events in bone morphogenesis is the condensation of embryonic
      mesenchymal cells into chondroblasts and their subsequent proliferation and
      differentiation into chondrocytes. During this time, certain signaling cascades
      operate to establish proper patterning and differentiation of the cartilaginous
      skeleton. Characterization of the signaling pathways involved in these processes
      remains to be accomplished. We have identified a novel murine cytosolic tyrosine
      phosphatase termed PTPPBS gamma (+/-) which is a member of the PTP PC12,Br7,Sl
      (PTPPBS) family. Spatio-temporal expression analysis of the members of this
      tyrosine phosphatase family demonstrates significant expression of the gamma (-)
      splice variant in the cartilaginous skeleton. Using an embryonic mandibular
      explant culture system to serve as a model for cartilage formation, we examined
      the potential roles of the PTPPBS gamma phosphatase by loss-of-function studies
      achieved with antisense oligodeoxynucleotides. These studies demonstrated that
      loss of expression of the PTPPBS gamma (-) isoform resulted in abnormal
      patterning of Meckel's cartilage and an increase in the size of the chondrogenic
      regions. In gamma antisense-treated explants, bromodeoxyuridine-pulse labeling
      studies revealed increased proliferation of chondroblasts bordering along
      precartilaginous condensations and bordering populations of maturing
      chondrocytes. These studies provide evidence that in early skeletal development,
      PTPPBS gamma may regulate the rate of chondroblast proliferation in the
      cartilaginous skeleton.

PMID- 10949046
TI  - Conversion of red blood cells (RBCs) from the larval to the adult type during
      metamorphosis in Xenopus: specific removal of mature larval-type RBCs by
      apoptosis.
AB  - The conversion of hemoglobins (Hbs) and red blood cells (RBCs) from the larval to
      the adult type was monitored during normal metamorphosis in Xenopus laevis, and
      in artificially induced metamorphosis-arrested and precociously metamorphosed
      animals by means of SDS-PAGE, Hb immunohistochemistry, and double-staining with
      in situ DNA nick-end labeling (TUNEL) for detection of apoptosis and Hb
      immunostain. During normal metamorphosis, larval RBCs gradually decreased and,
      conversely, adult RBCs increased in number. However, in metamorphosis-arrested
      tadpoles, the larval-adult conversion of RBCs did not occur within 4 weeks, but
      did rather within 6 months after the controls metamorphosed. In order to identify
      possible mechanisms for the specific removal of larval RBCs from circulation in
      metamorphosing and metamorphosed animals, double-staining experiments with TUNEL
      and Hb immunostain were carried out. During metamorphic climax, many larval RBCs
      expressed TUNEL-positive reactions in the spleen, suggesting that the larval RBCs
      were specifically removed from the spleen during metamorphosis. When the larval
      RBCs were transferred to the circulatory system of histocompatible control
      adults, they survived for a long time, and no transferred RBCs showed TUNEL
      positive reactions. In contrast, larval RBCs transferred to histocompatible
      adults that had been treated with T3 were reduced in number in the circulatory
      system of the recipients. Double-staining experiments demonstrated that the
      transferred larval RBCs underwent apoptosis in the spleen and liver of the adult
      recipients treated with T3, indicating that the mature larval-type RBCs were
      specifically removed from metamorphosing animals by apoptotic cell death under
      the influence of THs.

PMID- 10949047
TI  - Role of chondrogenic tissue in programmed cell death and BMP expression in chick
      limb buds.
AB  - In the developing chick leg bud, massive programmed cell death occurs in the
      interdigital region. Previously, we reported the inhibition of cell death by
      separation of the interdigital region from neighboring digit cartilage. In this
      study, we examined the relationship between cell death and cartilaginous tissue
      in vitro. First, cell fate was observed with DiI that was used to examine cell
      movement in the distal tip of leg bud. Labeled cells in the prospective digital
      region were distributed only in the distal region as a narrow band, while cells
      in the prospective interdigital region expanded widely in the interdigit. In
      coculture of monolayer cells and a cell pellet tending to differentiate into
      cartilage, monolayer cells migrated into the cell pellet. These results suggested
      that digit cartilage tends to recruit neighboring cells into the cartilage during
      limb development. Next, we observed the relationship between cell death and
      chondrogenesis in monolayer culture. Apoptotic cell death that could be detected
      by TUNEL occurred in regions between cartilaginous nodules in mesenchymal cell
      culture. More apoptotic cell death was detected in the cell culture of leg bud
      mesenchyme of stage 25/26 than that of leg bud mesenchyme of stage 22 or that of
      stage 28. The most developed cartilaginous nodules were observed in the cell
      culture of stage 25/26. Finally, we observed Bmp expression in vitro and in vivo.
      Bmp-2, Bmp-4 and Bmp-7 were detected around the cartilage nodules. When the
      interdigit was separated from neighboring digit cartilage, Bmp-4 expression
      disappeared near the cut region but remained near the digit cartilage. This
      correlation between cell death and cartilaginous region suggests that cartilage
      tissue can induce apoptotic cell death in the developing chick limb bud due to
      cell migration accompanying chondrogenesis and Bmp expression.

PMID- 10949048
TI  - Inhibition of apoptosis in the primary enamel knot does not affect specific tooth
      crown morphogenesis in the mouse.
AB  - The enamel knot (EK), located in the center of cap-stage tooth germs, is a
      transitory cluster of non-dividing epithelial cells, eventually linked to the
      outer dental epithelium by the enamel septum (ES). It might act as a signaling
      center providing positional information for tooth morphogenesis and could
      regulate the growth of tooth cusps through the induction of secondary signaling
      EKs. The EK undergoes apoptosis, which could constitute a mechanism whereby the
      signaling functions of this structure are terminated. Recently, we demonstrated
      the segregation of 5-bromo-2'-deoxyuridine (BrdU) negative inner dental
      epithelial (IDE) cells of the EK into as many individual groups of cells as cusps
      will form and suggested a morphogenetic role for these particular IDE cells.
      Using Z-VAD-fmk, a specific caspase inhibitor, apoptosis in the primary EK of
      first mouse lower cap-staged molars and lower incisors cultured in vitro was
      abrogated. No obvious histological alterations were observed in the incisors,
      whereas a prominent EK and an ES connecting the outer dental epithelium (ODE) and
      the BrdU negative IDE cells capping cusp L2 were observed in the molars. EK
      specific transcription (Shh, Msx-2, Bmp-2, Bmp-4) was down-regulated in the body
      of these structures with the exception of the associated IDE cells. In these
      experimental conditions, segregation of non-dividing transcriptionally active IDE
      cells occurred and a normal cusp pattern was expressed.

PMID- 10949049
TI  - The TGF-beta type III receptor is localized to the medial edge epithelium during
      palatal fusion.
AB  - During palatal fusion, the medial edge epithelial cells (MEE) but not the
      oral/nasal palatal epithelium, selectively undergo epithelial-mesenchymal
      transformation. It is known that this process is regulated, at least in part, by
      endogenous TGF-beta3. One conceivable mechanism is that restricted expression of
      TGF-beta receptors (TbetaRs) in a subpopulation of cells may localize TGF-beta
      responsiveness (Brown et al., 1999). However, TGF-beta type II receptor (TbetaR
      II) is expressed by all palatal epithelial cells during palatal fusion (Cui et
      al., 1998) and therefore cannot localize TGF-beta3 responsiveness. To investigate
      the role of TGF-beta type III receptor (TbetaR-III) in MEE transformation, we
      examined the expression pattern of TbetaR-III in the developing palate from E12
      to E15 mice in vivo and in vitro by immunohistochemistry and compared the
      expression pattern to that of type I receptor (TbetaR-I). The expression of
      TbetaR-III was temporo-spatially restricted to the MEE during palatal fusion,
      while the expression of TbetaR-I was primarily localized in all palatal
      epithelia, consistent with the expression patterns of TbetaR-II and TGF-beta3
      (Cui et al., 1998). These results support our hypothesis that TbetaR-III
      localizes and mediates the developmental role of TGF-beta3 on MEE transformation
      by specific expression in the MEE. TbetaR-III may modulate TGF-beta3 binding to
      TbetaR-II in the MEE cells to locally enhance TGF-beta3 autocrine signaling
      through the TbetaR-I/TbetaR-II receptor complex, which contributes to MEE
      selective epithelial-mesenchymal transformation.

PMID- 10949050
TI  - Effects of hepatocyte growth factor anti-sense oligodeoxynucleotides or met D/D
      genotype on mouse molar crown morphogenesis.
AB  - Hepatocyte growth factor (HGF) is considered to be one of the mediators of
      epithelio-mesenchymal interactions during early organogenesis and to be also
      involved in the development of murine molars. In the developing tooth, HGF is
      expressed in the cells of the dental papillae, and c-Met, its receptor, in the
      cells of dental epithelia. In order to study the functional role played by HGF in
      tooth development, we tested the effects of HGF translation arrest by anti-sense
      phosphorothioate oligodeoxynucleotides on E-14 molars cultured in vitro. We also
      analyzed the histo-morphogenesis and crown cytodifferentiation of transgenic met
      E-14 molars cultured in vitro. 3D reconstructions revealed perturbations of the
      cusp pattern. However, histo-morphogenesis and crown cytodifferentiation were
      normal at the histological level.

PMID- 10949051
TI  - Effect of genistein alone and in combination with okadaic acid on the cell cycle
      resumption of mouse oocytes.
AB  - Our biopharmacological approach suggests that the now well-documented inhibitory
      effects of genistein on the maturation of mammalian oocytes do not seem to be
      related to its effect on tyrosine kinases. Indeed, we show that both tyrphostin
      B46 and Lavendustin A, two selective inhibitors of protein tyrosine kinases, fail
      to inhibit meiosis reinitiation. According to recent findings, the G2/M arrest
      induced by genistein could be due to inhibition of the kinase activity of cdc2.
      We were therefore mainly interested in dissecting the cytological effects of
      genistein on mouse primary and secondary oocytes. Genistein exerts the same
      cytological effects as IBMX on primary oocytes: their germinal vesicle is
      maintained in a central position, the cytoplasmic microtubule network is
      stabilized, the central GV immobilization is overcome by demecolcine and they
      complete normal maturation after their transfer to culture medium. The GV
      arresting activity of genistein is also bypassed by OA but combination of both
      drugs results in a dramatic reorganization of the cytoskeleton leading to a huge
      membrane bulging, which is quite different to apoptotic-related blebbing. MAP
      Kinase activation is correlated with meiosis reinitiation. When applied after
      GVBD has taken place, genistein does not inhibit MAPK activation, metaphase
      spindle formation and metaphase-to-anaphase transition, but prevents the barrel
      shaped MI spindle from undergoing its peripheral migration and the oocytes from
      extruding their first polar body. It may thus be concluded that the checkpoint
      control for anaphase onset is unaffected by the drug. On the contrary, our
      results suggest that spindle anaphase A to spindle anaphase B transition, spindle
      degradation, mid-body formation and cytokinesis are triggered by a genistein
      sensitive mechanism that might be a mid-anaphase checkpoint. Finally, we confirm
      that genistein induces transition to interphase in metaphase II oocytes but never
      induces cortical granule exocytosis, the cytoplasmic hallmark of activation.

PMID- 10949052
TI  - M-calpain levels increase during fusion of myoblasts in the mutant muscular
      dysgenesis (mdg) mouse.
AB  - Previous studies have led to the hypothesis of a possible role for the calcium
      dependent neutral protease m-calpain in myoblast fusion in culture. To evaluate
      this hypothesis, we chose as our model, the "muscular dysgenesis" mouse (mdg),
      which presents in vivo and in vitro characteristics of an elevated process of
      fusion (Yao and Essien, 1975; Dussartre, 1993; Ashby et al., 1993, Joffroy et
      al., 1999). The aim of this study was to demonstrate using myoblast cell lines
      and muscle biopsies from this mdg mutant, that the amount of m-calpain increases
      significantly as multinucleated myotubes are formed. Using immunoblot analysis,
      it was shown that the m-calpain concentration in a dysgenic cell line (GLT)
      increased 3-fold compared to what it was upon the introduction of the
      differentiation medium. On the other hand, in a normal cell line (NLT), the
      concentration of m-calpain did not vary significantly. Thus, when the transition
      from myoblasts to myotubes was slow, and the absolute level of fusion was
      reduced, as in the NLT cell line, the level of m-calpain was stable. In contrast,
      when the process of fusion was precocious and fast, and the level of fusion was
      elevated, such as in the GLT cell line, the concentration of m-calpain increased
      during fusion. Moreover, when myoblast fusion was prevented by the addition of
      calpain inhibitor II, the process was reduced by approximately 93%. Taking into
      account these observations, it is clear from our data that the muscular
      dysgenesis mouse provides a relevant model to study myoblast fusion and that m
      calpain is involved in this process.

PMID- 10949053
TI  - The human red nucleus and lateral cerebellum in supporting roles for sensory
      information processing.
AB  - A functional MRI study compared activation in the red nucleus to that in the
      lateral cerebellar dentate nucleus during passive and active tactile
      discrimination tasks. The study pursued recent neuroimaging results suggesting
      that the cerebellum may be more associated with sensory processing than with the
      control of movement for its own sake. Because the red nucleus interacts closely
      with the cerebellum, the possibility was examined that activity in red nucleus
      might also be driven by the requirement for tactile sensory processing with the
      fingers rather than by finger movement alone. The red and dentate nuclei were
      about 300% more active (a combination of activation areas and intensities) during
      passive (non-motor) tactile stimulation when discrimination was required than
      when it was not. Thus, the red nucleus was activated by purely sensory stimuli
      even in the absence of the opportunity to coordinate finger movements or to use
      the sensory cues to guide movement. The red and dentate nuclei were about 70%
      more active during active tactile tasks when discrimination was required than
      when it was not (i.e., for simple finger movements alone). Thus, the red nucleus
      was most active when the fingers were being used for tactile sensory
      discrimination. In both the passive and active tactile tasks, the observed
      activation had a contralateralized pattern, with stronger activation in the left
      red nucleus and right dentate nucleus. Significant covariation was observed
      between activity in the red nucleus and the contralateral dentate during the
      discrimination tasks and no significant correlation between the red nucleus and
      the contralateral dentate activity was detected during the two non-discrimination
      tasks. The observed interregional covariance and contralateralized activation
      patterns suggest strong functional connectivity during tactile discrimination
      tasks. Overall, the pattern of findings suggests that the activity in the red
      nucleus, as in the lateral cerebellum, is more driven by the requirements for
      sensory processing than by motor coordination per se.

PMID- 10949054
TI  - A multistep unsupervised fuzzy clustering analysis of fMRI time series.
AB  - A paradigm independent multistage strategy based on the Unsupervised Fuzzy
      Clustering Analysis (UFCA) and its potential for fMRI data analysis are
      presented. The influence of the fuzziness index is studied using Receiver
      Operating Characteristics (ROC) methodology and an interval of choice, around the
      widely used value 2, is shown to yield the best performance. The ill-balanced
      data problem is also overcome using a pre-processing step to reduce the number of
      voxels presented to the method. Statistical and anatomical criteria are proposed
      to exclude some voxels and enhance the UFCA sensitivity. An original
      postprocessing step aiming at statistically characterizing the obtained clusters
      is also developed. Two similarity criteria are used: the correlation coefficient
      on temporal profiles and a novel fuzzy overlap coefficient on membership degree
      maps. This final step provides a useful analysis tool to study intra-individual
      reproducibility of the classes across series (stimulation vs. stimulation, noise
      vs. noise or stimulation vs. noise). Finally, a comparison between this technique
      and some existing or locally developed postprocessing algorithms is presented
      using ROC methods. Its sensitivity and robustness is compared to the classical
      FCA or other techniques as a function of several parameters such as Contrast-to
      Noise Ratio (CNR) and noise amplitude. Even without knowledge about the paradigm,
      the hemodynamic response function and the number of clusters, the performances of
      the proposed strategy are comparable to those of the classical approaches where
      extensive prior knowledge has to be added.

PMID- 10949055
TI  - Striatum forever, despite sequence learning variability: a random effect analysis
      of PET data.
AB  - This PET study is concerned with the what, where, and how of implicit sequence
      learning. In contrast with previous studies imaging the serial reaction time
      (SRT) task, the sequence of successive locations was determined by a
      probabilistic finite-state grammar. The implicit acquisition of statistical
      relationships between serially ordered elements (i.e., what) was studied scan by
      scan, aiming to evidence the brain areas (i.e., where) specifically involved in
      the implicit processing of this core component of sequential higher-order
      knowledge. As behavioural results demonstrate between- and within-subjects
      variability in the implicit acquisition of sequential knowledge through practice,
      functional PET data were modelled using a random-effect model analysis (i.e.,
      how) to account for both sources of behavioural variability. First, two mean
      condition images were created per subject depending on the presence or not of
      implicit sequential knowledge at the time of each of the 12 scans. Next, direct
      comparison of these mean condition images provided the brain areas involved in
      sequential knowledge processing. Using this approach, we have shown that the
      striatum is involved in more than simple pairwise associations and that it has
      the capacity to process higher-order knowledge. We suggest that the striatum is
      not only involved in the implicit automatization of serial information through
      prefrontal cortex-caudate nucleus networks, but also that it plays a significant
      role for the selection of the most appropriate responses in the context created
      by both the current and previous stimuli, thus contributing to better efficiency
      and faster response preparation in the SRT task.

PMID- 10949056
TI  - Perceptual priming and extrastriate cortex: consensus and controversy.

PMID- 10949057
TI  - Neuroanatomical organization of perceptual memory: an fMRI study of picture
      priming.
AB  - Neuroanatomical organization of perceptual representation in human memory system
      is unclear primarily because it has been studied using paradigms that have both,
      perceptual and conceptual components (e.g., word stem completion and word
      fragment completion). In the present experiment, functional magnetic resonance
      imaging (fMRI) technique was used to examine the pattern of cortical activation
      in a picture identification test in which subjects were asked to identify
      subliminally presented primed and novel pictures. This test is a modification of
      the word identification test that is considered a "pure" form of perceptual
      priming. Results indicate that perceptual priming is associated with reduced
      activation in the extrastriate cortex and that the memory for subliminally
      presented stimuli is processed by the same brain areas that process adequate
      stimuli. The activation pattern observed in picture identification test is
      different from that reported in the experiments of conceptual priming, suggesting
      that perceptual and conceptual representation of memory are supported by separate
      brain mechanisms.

PMID- 10949058
TI  - Rapid and effective correction of RF inhomogeneity for high field magnetic
      resonance imaging.
AB  - The well-known variability in the distribution of high frequency electromagnetic
      fields in the human body causes problems in the analysis of structural
      information in high field magnetic resonance images. We describe a method of
      compensating for the purely intensity-based effects. In our simple and rapid
      correction algorithm, we first use statistical means to determine the background
      image noise level and the edges of the image features. We next populate all
      "noise" pixels with the mean signal intensity of the image features. These data
      are then smoothed by convolution with a gaussian filter using Fourier methods.
      Finally, the original data that are above the noise level are normalized to the
      smoothed images, thereby eliminating the lowest spatial frequencies in the final,
      corrected data. Processing of a 124 slice, 256 x 256 volume dataset requires
      under 70 sec on a laptop personal computer. Overall, the method is less prone to
      artifacts from edges or from sensitivity to absolute head position than are other
      correction techniques. Following intensity correction, the images demonstrated
      obvious qualitative improvement and, when subjected to automated segmentation
      tools, the accuracy of segmentation improved, in one example, from 35.3% to 84.7%
      correct, as compared to a manually-constructed gold standard.

PMID- 10949059
TI  - DNA vaccination to treat autoimmune diabetes.
AB  - In numerous animal models, DNA immunization has been shown to induce protective
      immunity against infectious diseases (viral, bacterial and protozoan) and cancers
      (1, 2). In these situations it is desirable to induce a strong immune response to
      the DNA-encoded antigen in order to generate an immune memory that enables the
      vaccine to respond more rapidly to subsequent challenge. The success of DNA
      vaccination in this regard has led to its rapid introduction into several human
      clinical trials (3, 4). However, in autoimmunity, undesirable immune responses to
      autoantigens are thought to lead to the destruction of target cells or organs,
      resulting in diseases such as myasthenia gravis, diabetes or multiple sclerosis.
      Thus, at first sight, it appears that immunization would more likely trigger
      autoimmunity than ameliorate it. Nevertheless, clinical experience has shown that
      certain immune-mediated diseases may be countered by low-dose antigen
      administration ('desensitization'), although the underlying mechanisms remain
      somewhat conjectural. Here, we will describe an intriguing approach to the
      prevention of autoimmune disease, in which we use a DNA vaccine encoding a self
      antigen to abrogate autoimmune diabetes. The success of this strategy relies on
      the nature of the immune response induced by the DNA vaccine.

PMID- 10949060
TI  - Testing for endothelial dysfunction.
AB  - Endothelial health is a key factor in normal cardiovascular homeostasis, and
      recent studies have revealed several important functions of the vascular
      endothelium that protect against atherothrombosis. These include control over
      arterial tone, coagulation, fibrinolysis, and vascular growth. Consequently,
      endothelial dysfunction has been implicated as an important event in the
      pathogenesis of atherosclerosis, coronary vasoconstriction, hypertension, and
      myocardial ischaemia. Therefore, there has been considerable research interest in
      diagnostic assays for the assessment of endothelium. This review outlines the
      current status of markers of endothelial dysfunction, particularly those related
      to vasomotor control, as well as circulating markers of vascular health.

PMID- 10949061
TI  - Evidence-based data on pain relief with antidepressants.
AB  - This structured review addresses the issue of whether antidepressants have an
      antinociceptive (analgesic) effect for chronic pain independent of their
      antidepressant effect. In order to answer this question, human acute pain
      studies, individual placebo-controlled studies for the treatment of specific
      chronic pain syndromes, and metaanalytic studies were reviewed and placed into
      table format. Analysis of this evidence led to the following conclusions: The
      evidence was consistent in indicating that overall antidepressants may have an
      antinociceptive effect in chronic pain, and that these drugs were effective for
      neuropathic pain. There was also some evidence that these drugs could be
      effective for psychogenic or somatoform disorder-associated pain. This evidence
      also strongly suggested that serotonergic-noradrenergic antidepressants may have
      a more consistent antinociceptive effect than the serotonergic antidepressants.
      Finally, this evidence indicated that antidepressants could be effective for pain
      associated with some specific pain syndromes, such as chronic low back pain,
      osteoarthritis or rheumatoid arthritis, fibrositis or fibromyalgia, and ulcer
      healing. Possible reasons for the conflicting results of studies in this area are
      presented, and problems that could limit the validity of the conclusions of this
      review are discussed.

PMID- 10949062
TI  - Dangers of growth hormone therapy in critically ill patients.
AB  - Prolonged stay of patients is the major challenge for modern intensive care
      because of its effects on morbidity and resource utilization. Severe trauma or
      infection are associated with the catabolic response, characterized by increased
      protein turnover and negative nitrogen balance. Severe catabolism leads to end
      organ dysfunction and muscular weakness prolonging the need for mechanical
      ventilation. Catabolism cannot be prevented with standard parenteral or enteral
      nutritional formulas. In order to prevent the complications of catabolism in
      intensive care patients, recombinant growth hormone (rhGH) has been applied
      during two decades as an experimental therapy for patients requiring parenteral
      nutrition and for those with respiratory failure. Administration of rhGH has
      resulted in positive nitrogen balance, and studies in mechanically ventilated
      patients suggest that it may shorten the need for ventilatory support. In
      contrast to the results of these relatively small studies, a recent multinational
      randomized controlled trial revealed that the administration of rhGH (with doses
      10-20 times higher than those used for replacement therapy) increases the
      mortality of critically ill patients. This excessive mortality in patients
      treated with rhGH was related to infections and development of multiple organ
      failure. Administration of high doses of rhGH to critically ill patients cannot
      thus be recommended.

PMID- 10949063
TI  - Psychosomatic medicine: state of the art.
AB  - Contemporary psychosomatic medicine must take into consideration developments in
      psychobiology. The difficulty in accepting dualistic concepts is a serious
      challenge to positions distinguishing between psychological and 'real' causes of
      disease. There is more emphasis on life style factors for disease and on the
      impact of psychosocial factors on illness rather than on disease. The
      neurophysiological concept of activation or arousal has been important in the
      development of rational pathophysiological models that describe how sustained
      arousal may be a pathophysiological factor. For illness, sensitization may be an
      acceptable psychobiological mechanism underlying very frequently occurring and
      expensive medical conditions that require medical and economical assistance. One
      possible alternative to old dynamic concepts is the development of a cognitive
      arousal theory of stress.

PMID- 10949064
TI  - Cardiovascular psychophysiology.
AB  - Both environmental and predispositional factors are of importance in the
      pathogenesis of cardiovascular (CV) disease. In humans, it is difficult to
      characterize the pathogenic environmental factors (exposures) because of the long
      time-span of pathogenesis. Perceived effort, control, social isolation, and
      absence of reward seem to increase the risk of CV diseases. It is
      methodologically easier to measure predispositional factors at one point in time
      and then record disease after some years; and there are several reports of
      associations between personality traits or behaviour patterns and CV disease.
      Recent psychophysiological research has focused on CV hyper-reactivity to
      challenge. Hyperreactivity seems to be common in the offspring of hypertensives.
      This relation may be psychophysiological rather than physiological. Several
      questions remain regarding the validity and reliability of the hyper-reactivity
      construct. Studies of social hierarchies in animals have shown that social
      interactions produce pronounced psychophysiological responses. The existence of
      several differentiated CV response patterns may explain the contradictory
      findings of studies that only measure one or few physiological parameters.
      Predisposition to behaviours and reactivity of physiological systems may be
      accentuated by dominance-subordinate interactions. The availability of control
      and the perception of mastery is crucial in terminating responding to stressors.
      The presence of relatively constant response patterns to social interactions
      suggests that social interactions must be taken into account. Focus of CV
      psychophysiology should shift to studies of behavioural and somatic responses
      during social interactions.

PMID- 10949065
TI  - Concepts and methodology of psychosomatic research: facing the complexity.
AB  - This review describes and discusses firstly the main characteristics and problems
      of psychosomatic research. One of the main problems is the validity of laboratory
      stressors in real-life situations. Secondly, it outlines the main philosophy and
      current concepts of psychosomatic medicine. The basic idea of a new integrative
      psychosomatic model is given. Thirdly, it presents some new methods that can be
      of use in psychosomatic research as well as research findings of special interest
      to cardiology. Especially the relationship between depression and coronary heart
      disease is discussed. The conclusion is that new methods and technical
      possibilities have great potential in enhancing psychosomatic research.

PMID- 10949066
TI  - Physiological basis for human autonomic rhythms.
AB  - Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve
      activity have been studied intensively in recent years to explore otherwise
      obscure human neurophysiological mechanisms. The best-studied rhythms are those
      occurring at breathing frequencies. Published evidence indicates that respiratory
      fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R
      intervals result primarily from the action of a central 'gate' that opens during
      expiration and closes during inspiration. Parallel respiratory fluctuations of
      arterial pressures and R-R intervals are thought to be secondary to arterial
      baroreflex physiology: changes in systolic pressure provoke changes in the R-R
      interval. However, growing evidence suggests that these parallel oscillations
      result from the influence of respiration on sympathetic and vagal-cardiac
      motoneurones rather than from baroreflex physiology. There is a rapidly growing
      literature on the use of mathematical models of low- and high-frequency
      (respiratory) R-R interval fluctuations in characterizing instantaneous
      'sympathovagal balance'. The case for this approach is based primarily on
      measurements made with patients in upright tilt. However, the strong linear
      relation between such measures as the ratio of low- to high-frequency R-R
      interval oscillations and the angle of the tilt reflects exclusively the
      reductions of the vagal (high-frequency) component. As the sympathetic component
      does not change in tilt, the low- to high-frequency R-R interval ratio provides
      no proof that sympathetic activity increases. Moreover, the validity of
      extrapolating from measurements performed during upright tilt to measurements
      during supine rest has not been established. Nonetheless, it is clear that
      measures of heart rate variability provide important prognostic information in
      patients with cardiovascular diseases. It is not known whether reduced heart rate
      variability is merely a marker for the severity of disease or a measurement that
      identifies functional reflex abnormalities contributing to terminal dysrhythmias.

PMID- 10949067
TI  - The brain-heart axis in the perception of cardiac pain: the elusive link between
      ischaemia and pain.
AB  - Angina pectoris is a common symptom and one that can have profound implications
      for the patient. However, it correlates poorly with the extent of myocardial
      ischaemia and with prognosis. In order to understand more fully the heterogeneity
      of the experience of chest pain, we have adopted the technique of functional
      neuroimaging, where positron emission tomography is used to measure regional
      cerebral blood flow as an index of regional neuronal activation, during
      myocardial ischaemia in patients with coronary artery disease. We have been able
      to delineate those brain areas that are involved in the perception of angina: the
      hypothalamus, periaquaductal grey, thalami and bilaterally the prefrontal cortex
      and in the left the inferior anterocaudal cingulate cortex. By studying patients
      with silent myocardial ischaemia, we have established that the silence is not
      merely a matter of impaired afferent signalling resulting from autonomic
      neuropathy, but that it is associated with a failure of transmission of signals
      from the thalamus to the frontal cortex. At the other end of the spectrum, we
      have studied patients with syndrome X, a condition of chest pain with ischaemic
      like stress electrocardiography (ECG) but entirely normal coronary angiogram; (on
      the basis of our own and other data we consider an ischaemic aetiology to be most
      unlikely in this condition). In syndrome X, distinct patterns of cerebral
      activation were found with characteristic activation of the right anterior insula
      at its junction with the frontal operculum. In conclusion, we present a unified
      view of the cerebral handling of afferent signals from the heart throughout this
      spectrum of experience of chest pain, a view that accounts for the clinical
      features of the patients studied.

PMID- 10949068
TI  - The changing face of sympathetic overactivity in hypertension.
AB  - There is a lot of evidence showing that sympathetic activity is increased in a
      large proportion of patients with hypertension. However, the clinical impact of
      this state is frequently underestimated. Several factors seem to be
      misunderstood, such as whether sympathetic overactivity is reproducibly present,
      whether it lasts throughout 24 h, and what is the significance of its association
      with tachycardia. In this review, we present data to indicate that several
      haemodynamic changes in hypertension such as elevated cardiac output and heart
      rate and alteration in vascular resistance are neurogenic. The relationship
      between the increased sympathetic tone and decreased parasympathetic tone in
      hypertension is reciprocal, which strongly suggests that the abnormality emanates
      from the brain. The increase in sympathetic drive in hypertension is widespread
      across many organs. Beside the heart it is seen in the kidney and skeletal
      muscle, and even in platelets. We also discuss the possible mechanisms of the
      haemodynamic transition from this hyperkinetic state to established hypertension.
      We propose a hypothesis where down-regulation of beta-adrenergic responsiveness
      plays a major role in explaining the haemodynamic changes as well as metabolic
      alterations, such as hyperinsulinaemia and even the gain of weight in
      hypertension. Thus, the increased sympathetic tone may be involved in the genesis
      of multiple, pressure-independent coronary risk factors in hypertension.

PMID- 10949069
TI  - Psychosocial factors in the development of hypertension.
AB  - The role of psychosocial factors in human hypertension is being investigated with
      three research strategies: epidemiological studies of blood pressure,
      psychological characteristics and life experience in population samples,
      naturalistic studies of the covariation between blood pressure, psychological
      state and everyday life events, and experimental studies of cardiovascular and
      neuroendocrine responses to behavioural stimuli. This article summarizes recent
      research on hypertension and psychological traits, job characteristics and social
      support, emphasizing the convergent knowledge deriving from complementary
      research strategies. The roles of stress-induced cardiovascular responses and
      prejudicial life styles in mediating influences on risk of hypertension are
      discussed.

PMID- 10949070
TI  - Signal transduction mechanisms mediating secretion in goldfish gonadotropes and
      somatotropes.
AB  - The intracellular signal transduction mechanisms mediating maturational
      gonadotropin and somatotropin secretion in goldfish are reviewed. Several major
      signaling mechanisms, including changes in intracellular [Ca2+], arachidonic acid
      cascades, protein kinase C, cyclic AMP/protein kinase A, calmodulin, nitric
      oxide, and Na+/H+ antiport, are functional in both cell types. However, their
      relative importance in mediating basal secretion and neuroendocrine-factor
      regulated hormone release differs according to cell type. Similarly, agonist- and
      cell-type-specificity are also present in the transduction pathways leading to
      neuroendocrine factor-modulated maturational gonadotropin and somatotropin
      release. Specificity is present not only in the actions of different regulators
      within the same cell type and with the same ligand in the two cell types, but
      this also exists between isoforms of the same neuroendocrine factor within a
      single cell type. Other evidence suggests that function-selectivity of signaling
      may also result from differential modulation of Ca2+ fluxes from different
      sources. The interaction of different second messenger systems provide the basis
      by which regulation of maturational gonadotropin and somatotropin release by
      multiple neuroendocrine factors can be integrated at the target cell level.

PMID- 10949071
TI  - Transcriptional repression of TRH promoter function by T3: analysis by in vivo
      gene transfer.
AB  - We consider how an integrated in vivo model can be used to study the specific
      transcriptional effects of specific receptors in neuroendocrine systems. Our
      example is the role of thyroid receptor (TR) isoforms in mediating negative
      feedback effects of T3 on TRH (thyrotropin releasing hormone) expression. The in
      vivo transfection method employed polyethylenimine (PEI) to introduce genes
      directly into specific regions of the brains of mice, rats, and Xenopus tadpoles.
      In the mouse model, the technique has served to examine TR effects on TRH
      transcription and on the pituitary-thyroid axis end point: thyroid hormone
      secretion. When a TRH-luciferase construct is introduced into the hypothalami of
      newborn mice TRH-luciferase transcription is regulated physiologically, being
      significantly increased in hypothyroidism and decreased in T3-treated animals.
      When various T3-binding forms of TRbeta or TRalpha are expressed in the
      hypothalamus, all TRbeta isoforms give T3-dependent regulation of TRH
      transcription, whereas TRalpha isoforms block T3-dependent transcription.
      Moreover, TR transcriptional effects are correlated with physiological
      consequences on circulating T4. Thus, somatic gene transfer shows TR subtypes to
      have distinct, physiologically relevant effects on TRH transcription. The
      approach is an appealing alternative to germinal transgenesis for studying
      specific neuroendocrine regulations at defined developmental stages in different
      species.

PMID- 10949072
TI  - The role of glutamate and nitric oxide in the reproductive neuroendocrine system.
AB  - The preovulatory surge of gonadotropin releasing hormone (GnRH) is essential for
      mammalian reproduction. Recent work has implicated the neurotransmitters
      glutamate and nitric oxide as having a key role in this process. Large
      concentrations of glutamate are found in several hypothalamic nuclei known to be
      important for GnRH release and glutamate receptors are also located in these key
      hypothalamic nuclei. Administration of glutamate agonists stimulate GnRH and LH
      release, while glutamate receptor antagonists attenuate the steroid-induced and
      preovulatory LH surge. Glutamate has also been implicated in the critical
      processes of puberty, hormone pulsatility, and sexual behavior. Glutamate is
      believed to elicit many of these effects by activating the release of the gaseous
      neurotransmitter, nitric oxide (NO). NO potently stimulates GnRH by activating a
      heme containing enzyme, guanylate cyclase, which in turn leads to increased
      production of cGMP and GnRH release. Recent work has focused on identifying
      anchoring and (or) clustering proteins that target glutamate receptors to the
      synapse and couple the glutamate-NO neurotransmission system. The present review
      will discuss these new findings, as well as the role of glutamate and nitric
      oxide in important mammalian reproductive events, with a focus on the
      hypothalamic control of preovulatory GnRH release.

PMID- 10949073
TI  - Basic mechanisms of secretion: sorting into the regulated secretory pathway.
AB  - Targeting proteins to their correct cellular location is crucial for their
      biological function. In neuroendocrine cells, proteins can be secreted by either
      the constitutive or the regulated secretory pathways but the mechanism(s) whereby
      proteins are sorted into either pathway is unclear. In this review we discuss the
      possibility that sorting is either an active process occurring at the level of
      the trans-Golgi network, or that sorting occurs passively in the immature
      granules, The possible involvement of protein-lipid interactions in the sorting
      process is also raised.

PMID- 10949074
TI  - The caudal neurosecretory system: control and function of a novel neuroendocrine
      system in fish.
AB  - The caudal neurosecretory system (CNSS) of fish was first defined over 70 years
      ago yet despite much investigation, a clear physiological role has yet to be
      elucidated. Although the CNSS structure is as yet thought to be confined to
      piscine species, the secreted peptides, urotensins I and II (UI and UII), have
      been detected in a number of vertebrate species, most recently illustrated by the
      isolation of UII in humans. The apparent importance of these peptides, suggested
      by their relative phylogenetic conservation, is further supported by the complex
      control mechanisms associated with their secretion. The CNSS in teleosts is known
      to receive extensive and diverse innervation from the higher central nervous
      system, with evidence for the presence of cholinergic, noradrenergic,
      serotonergic, and peptidergic descending inputs. Recent observations also suggest
      the presence of glucocorticoid receptors in the flounder CNSS, supporting
      previous evidence for a possible role as a pituitary-independent mechanism
      controlling cortisol secretion. The most convincing evidence as to a
      physiological role for the CNSS in fish has stemmed from the direct and indirect
      influence of the urotensins on osmoregulatory function. Recent advances allowing
      the measurement of circulating levels of UII in the flounder have supported this.
      In addition, there is evidence to suggest some seasonal variation in peptide
      levels supporting the notion that the CNSS may have an integrative role in the
      control of coordinated changes in the reproductive, osmoregulatory and
      nutritional systems of migratory euryhaline species.

PMID- 10949075
TI  - Molecular integration of hypothalamo-pituitary-adrenal axis-related neurohormones
      on the GnRH neuron.
AB  - Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is pivotal
      to the regulation of reproductive physiology in vertebrates. GnRH and the
      reproductive axis, in general, can be inhibited during periods of stress or
      injury. Stress, in the form of mechanical, psychological or immunological insult
      to an organism results in the activation of the hypothalamo-pituitary-adrenal
      (HPA) axis initiated by the hypothalamic release of corticotropin-releasing
      factor (CRF). Recent studies indicate that CRF may act either directly on the
      GnRH neuron to down-regulate GnRH synthesis, or indirectly via a beta-endorphin
      mediated pathway. Moreover, in vitro studies suggest that CRF-related peptides
      can increase the sensitivity of the GnRH neuron to prolactin by increasing the
      synthesis of the prolactin receptor.

PMID- 10949076
TI  - Function- and agonist-specific Ca2+ signalling: the requirement for and mechanism
      of spatial and temporal complexity in Ca2+ signals.
AB  - Calcium signals have been implicated in the regulation of many diverse cellular
      processes. The problem of how information from extracellular signals is delivered
      with specificity and fidelity using fluctuations in cytosolic Ca2+ concentration
      remains unresolved. The capacity of cells to generate Ca2+ signals of sufficient
      spatial and temporal complexity is the primary constraint on their ability to
      effectively encode information through Ca2+. Over the past decade, a large body
      of literature has dealt with some basic features of Ca2+-handling in cells, as
      well as the multiplicity and functional diversity of intracellular Ca2+ stores
      and extracellular Ca2+ influx pathways. In principle, physiologists now have the
      necessary information to attack the problem of function- and agonist-specificity
      in Ca2+ signal transduction. This review explores the data indicating that Ca2+
      release from diverse sources, including many types of intracellular stores,
      generates Ca2+ signals with sufficient complexity to regulate the vast number of
      cellular functions that have been reported as Ca2+-dependent. Some examples where
      such complexity may relate to neuroendocrine regulation of hormone
      secretion/synthesis are discussed. We show that the functional and spatial
      heterogeneity of Ca2+ stores generates Ca2+ signals with sufficient
      spatiotemporal complexity to simultaneously control multiple Ca2+-dependent
      cellular functions in neuroendocrine systems.

PMID- 10949077
TI  - The role of amino acid neurotransmitters in the regulation of pituitary
      gonadotropin release in fish.
AB  - Both glutamate and gamma-aminobutyric acid (GABA) are involved in pituitary
      hormone release in fish. Glutamate serves 2 purposes, both as a neurotransmitter
      and as a precursor for GABA synthesis. Glutamate can be catabolized to GABA by
      the actions of 2 distinct but related enzymes, glutamate decarboxylase 65 (GAD65)
      and GAD67. They derive from 2 different genes that likely arose from an early
      gene duplication prior to the emergence of teleosts more than 400 million years
      ago. There is good evidence for the involvement of GABA in luteinizing hormone
      (LH) release in fish. The mechanism of GABA action to stimulate LH release
      appears to be a combination of effects on GnRH release, potentiation of
      gonadotropin hormone-releasing hormone (GnRH) action, and in some cases directly
      at the LH cell. These actions appear to be dependent on such factors as sex or
      sex steroid levels, and there may also be species differences. Nevertheless, the
      stimulatory effects of GABA on LH are present in at least 4 fish species. In
      contrast, convincing data for the inhibitory effects of GABA on LH release have
      only been observed in 1 fish species. The sites and mechanisms of action of amino
      acid neurotransmitters on LH release have yet to be fully characterized. Both
      130N-methyl-D-aspartic acid (NMDA) and S-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) type glutamate receptors are likely to have
      important roles. We suggest that it is a receptor similar to the GABA(A) type
      which mediates the effects of GABA on LH release in fish, at least partially
      acting on the GnRH neuron, but likely directly acting at the gonadotroph as well.
      GABA may also be involved in regulating the release of other pituitary hormones
      in fish, namely follicle stimulating hormone (FSH = GTH-I), prolactin, and growth
      hormone. Based on the findings described in this review, a working model for the
      involvement of glutamate and GABA in the regulation of LH release in teleost fish
      is proposed.

PMID- 10949078
TI  - Activins and their receptors in female reproduction.
AB  - Activins are growth and differentiation factors belonging to the transforming
      growth factor-beta superfamily. They are dimeric proteins consisting of two
      inhibin beta subunits. The structure of activins is highly conserved during
      vertebrate evolution. Activins signal through type I and type II receptor
      proteins, both of which are serine/threonine kinases. Subsequently, downstream
      signals such as Smad proteins are phosphorylated. Activins and their receptors
      are present in many tissues of mammals and lower vertebrates where they function
      as autocrine and (or) paracrine regulators of a variety of physiological
      processes, including reproduction. In the hypothalamus, activins are thought to
      stimulate the release of gonadotropin-releasing hormone. In the pituitary,
      activins increase follicle-stimulating hormone secretion and up-regulate
      gonadotropin-releasing hormone receptor expression. In the ovaries of
      vertebrates, activins are expressed predominantly in the follicular layer of the
      oocyte where they regulate processes such as folliculogenesis, steroid hormone
      production, and oocyte maturation. During pregnancy, activin-A is also involved
      in the regulation of placental functions. This review provides a brief overview
      of activins and their receptors, including their structures, expression, and
      functions in the female reproductive axis as well as in the placenta. Special
      effort is made to compare activins and their receptors in different vertebrates.

PMID- 10949079
TI  - Cytosensor techniques for examining signal transduction of neurohormones.
AB  - This review describes the principles of microphysiometry and how they can be
      applied, using the Cytosensor, to the investigation of the signal transduction
      mechanisms activated by both G-protein and non-G-protein coupled hormone and
      neuropeptide receptors. The use of the Cytosensor to study desensitisation and
      cross-talk is also discussed, as are the benefits and limitations of this
      technique.

PMID- 10949080
TI  - Prohormone transport through the secretory pathway of neuroendocrine cells.
AB  - En route through the secretory pathway of neuroendocrine cells, prohormones pass
      a series of membrane-bounded compartments. During this transport, the prohormones
      are sorted to secretory granules and proteolytically cleaved to bioactive
      peptides. Recently, progress has been made in a number of aspects concerning
      secretory protein transport and sorting, particularly with respect to transport
      events in the early regions of the secretory pathway. In this review we will deal
      with some of these aspects, including: i) selective exit from the endoplasmic
      reticulum via COPII-coated vesicles and the potential role of p24 putative cargo
      receptors in this process, ii) cisternal maturation as an alternative model for
      protein transport through the Golgi complex, and iii) the mechanisms that may be
      involved in the sorting of regulated secretory proteins to secretory granules.
      Although much remains to be learned, interesting new insights into the
      functioning of the secretory pathway have been obtained.

PMID- 10949081
TI  - Orexins (hypocretins): novel hypothalamic peptides with divergent functions.
AB  - The hypothalamus is the most important region in the control of food intake and
      body weight. The ventromedial "satiety center" and lateral hypothalamic "feeding
      center" have been implicated in the regulation of feeding and energy homeostasis
      by various studies of brain lesions. The discovery of orexin peptides, whose
      neurons are localized in the lateral hypothalamus and adjacent areas, has given
      us new insight into the regulation of feeding. Dense fiber projections are found
      throughout the brain, especially in the raphe nucleus, locus coeruleus,
      paraventricular thalamic nucleus, arcuate nucleus, and central gray. Orexins
      mainly stimulate food intake, but by the virtue of wide immunoreactive
      projections throughout the brain and spinal cord, orexins interact with various
      neuronal pathways to potentiate divergent functions. In this review, we summarize
      recent progress in the physiological, neuroanatomical, and molecular studies of
      the novel neuropeptide orexins (hypocretins).

PMID- 10949082
TI  - Corticosteroid actions from neuronal membrane to behavior: neurophysiological
      mechanisms underlying rapid behavioral effects of corticosterone.
AB  - Investigation of the rapid suppression of male courtship clasping behavior by
      corticosterone in roughskin newts (Taricha granulosa) has led to the
      identification of a specific neuronal membrane receptor for this stress steroid.
      This paper describes studies of the neurophysiological effects of the rapid,
      membrane receptor mediated action of corticosterone on neurons that are involved
      in the control of clasping. In freely behaving newts, medullary neurons,
      including reticulospinal neurons, process clasp-triggering sensory signals and
      participate in control of clasping movements. Corticosterone injection causes
      these brainstem neurons to show selective depression of clasping-related
      sensorimotor function. These corticosterone effects appear in 3-10 min and are
      closely associated with the simultaneous depression of clasping. In addition to
      these functionally specific effects, corticosterone simultaneously causes
      widespread, primarily depressive effects on neuronal activity and excitability in
      the medulla and elsewhere in the brain. Thus, the membrane actions of
      corticosterone lead to diverse neural effects, including changes in membrane
      excitability as well as specific, network-level actions that are apparent only
      during behavior. These rapid corticosterone effects strongly interact with
      actions of the neuropeptides vasotocin and corticotropin-releasing factor, such
      that the form and magnitude of the steroid's effects depend on the prevailing
      neuroendocrine state of the brain.

PMID- 10949083
TI  - Activity-dependent morphological synaptic plasticity in an adult neurosecretory
      system: magnocellular oxytocin neurons of the hypothalamus.
AB  - Oxytocin and vasopressin neurons, located in the supraoptic and paraventricular
      nuclei of the hypothalamus, send their axons to the neurohypophysis where the
      neurohormones are released directly into the general circulation. Hormone release
      depends on the electrical activity of the neurons, which in turn is regulated by
      different afferent inputs. During conditions that enhance oxytocin secretion
      (parturition, lactation, and dehydration), these afferents undergo morphological
      remodelling which results in an increased number of synapses contacting oxytocin
      neurons. The synaptic changes are reversible with cessation of stimulation. Using
      quantitative analyses on immunolabelled preparations, we have established that
      this morphological synaptic plasticity affects both inhibitory and excitatory
      afferent inputs to oxytocin neurons. This review describes such synaptic
      modifications, their functional significance, and the cellular mechanisms that
      may be responsible.

PMID- 10949084
TI  - Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic
      factor in fish.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of
      the secretin-glucagon peptide family. In mammals, this peptide has been located
      in a wide range of tissues and is involved in a variety of biological functions.
      In lower vertebrates, especially fish, increasing evidence suggests that PACAP
      may function as a hypophysiotropic factor regulating pituitary hormone secretion.
      PACAP has been identified in the brain-pituitary axis of representative fish
      species. The molecular structure of fish PACAP is highly homologous to mammalian
      PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it
      also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is
      under direct innervation of the hypothalamus and PACAP nerve fibers have been
      identified in the pars distalis. Using the goldfish as a fish model, mRNA
      transcripts of PACAP receptors, namely the PAC1 and VPACI receptors, have been
      identified in the pituitary as well as in various brain areas. Consistent with
      the pituitary expression of PACAP receptors, PACAP analogs are effective in
      stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the
      goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated
      via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase
      A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of
      Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+
      calmodulin protein kinase II is likely the downstream mechanism mediating PACAP
      stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the
      associated post-receptor signaling events responsible for PACAP-stimulated GTH-II
      release have not been characterized in goldfish, these findings support the
      hypothesis that PACAP is produced in the hypothalamus and delivered to the
      anterior pituitary to regulate GH and GTH-II release in fish.

PMID- 10949085
TI  - Interplay between liganded and orphan nuclear receptors controls reproductive
      pathways.
AB  - Nuclear receptors are transcription factors that belong to an evolutionary
      ancient superfamily. These proteins, which are even present in primitive
      metazoans, are implicated in all levels of cell fate: proliferation,
      differentiation, and apoptosis. Some of these nuclear receptors behave as ligand
      inducible transcription factors, as they have acquired during evolution the
      ability to bind ligands. This is the case for some proteins that recognize small
      hydrophobic signaling molecules, and particularly the estrogen receptor (ER or
      NR3A1), which regulates the target gene's transcription rate under estrogen
      binding. It is now known that the ER alone regulates the transcription of many
      genes, such as those implicated in reproductive functions. However, this ER
      mediated signaling pathway could be modulated by other transcription factors. Our
      work has established that two other orphan nuclear receptors (SF-1 or NR5A1 and
      the COUP-TFs, NR2F1 and NR2F2) can enhance two ER-regulated genes implicated in
      salmonid reproductive functions: the ER gene itself, and the sGTHIIbeta gene.
      Moreover, some xenoestrogens could disturb these regulations. Therefore, our data
      contribute to the concept that interplay between nuclear receptors is an
      important event for the transcriptional regulation of genes controlling cellular
      functions.

PMID- 10949086
TI  - Autocrine regulation of calcium influx and gonadotropin-releasing hormone
      secretion in hypothalamic neurons.
AB  - Gonadotropin-releasing hormone (GnRH) receptors are expressed in hypothalamic
      tissues from adult rats, cultured fetal hypothalamic cells, and immortalized GnRH
      secreting neurons (GT1 cells). Their activation by GnRH agonists leads to an
      overall increase in the extracellular Ca2+-dependent pulsatile release of GnRH.
      Electrophysiological studies showed that GT1 cells exhibit spontaneous,
      extracellular Ca2+-dependent action potentials, and that their inward currents
      include Na+, T-type and L-type Ca2+ components. Several types of potassium
      channels, including apamin-sensitive Ca2+-controlled potassium (SK) channels, are
      also expressed in GT1 cells. Activation of GnRH receptors leads to biphasic
      changes in intracellular Ca2+ concentration ([Ca2+]i), with an early and
      extracellular Ca2+-independent peak and a sustained and extracellular Ca2+
      dependent plateau phase. During the peak [Ca2+]i response, electrical activity is
      abolished due to transient hyperpolarization that is mediated by SK channels.
      This is followed by sustained depolarization and resumption of firing with
      increased spike frequency and duration. The agonist-induced depolarization and
      increased firing are independent of [Ca2+]i and are not mediated by inhibition of
      K+ currents, but by facilitation of a voltage-insensitive and store depletion
      activated Ca2+-conducting inward current. The dual control of pacemaker activity
      by SK and store depletion-activated Ca2+ channels facilitates voltage-gated Ca2+
      influx at elevated [Ca2+]i levels, but also protects cells from Ca2+ overload.
      This process accounts for the autoregulatory action of GnRH on its release from
      hypothalamic neurons.

PMID- 10949087
TI  - Neuropeptide Y family of peptides: structure, anatomical expression, function,
      and molecular evolution.
AB  - Evolutionary relationships between neuroendocrine peptides are often difficult to
      resolve across divergent phyla due to independent duplication events in different
      lineages. Thanks to peptide purification and molecular cloning in many different
      species, the situation is beginning to clear for the neuropeptide Y (NPY) family,
      which also includes peptide YY (PYY), the tetrapod pancreatic polypeptide (PP)
      and the fish pancreatic peptide Y (PY). It has long been assumed that the first
      duplication to occur in vertebrate evolution generated NPY and PYY, as both of
      these are found in all gnathostomes as well as lamprey. Evidence from other gene
      families show that this duplication was probably a chromosome duplication event.
      The origin of a second PYY peptide found in lamprey remains to be explained. Our
      recent cloning of NPY, PYY and PY in the sea bass proves that fish PY is a
      separate gene product. We favour the hypothesis that PY is a duplicate of the PYY
      gene and that it may have occurred late in fish evolution, as PY has so far only
      been found in acanthomorph fishes. Thus, this duplication seems to be independent
      of the one that generate PP from PYY in tetrapods, although both tetrapod PP and
      fish PY are expressed in the pancreas. Studies in the sea bass and other fish
      show that PY, in contrast to PP, is expressed in the nervous system. We review
      the literature on the distribution and functional aspects of the various NPY
      family peptides in vertebrates.

PMID- 10949088
TI  - Expression of purinergic P2X2 receptor-channels and their role in calcium
      signaling in pituitary cells.
AB  - Pituitary cells express purinergic receptor-channels (P2XR), the activation of
      which by ATP is associated with the facilitation of Ca2+ influx. Pharmacological,
      RT-PCR, and nucleotide sequence analyses confirm the presence of a wild type
      P2X2aR and a spliced isoform P2X2bR, which lacks a portion of carboxyl terminal
      amino acids. Wild type and spliced isoform receptors have a similar EC50 for ATP
      and time-course for activation, but the spliced isoform exhibits rapid and
      complete desensitization, whereas the wild type channel desensitizes slowly and
      incompletely. Deletion and insertion studies have revealed that a 6 residue
      sequence located in carboxyl tail (Arg371-Pro376) is required for sustained Ca2+
      influx through wild type receptors. When co-expressed, the wild type and spliced
      channels form functional heteropolymeric channels. The patterns of Ca2+ signaling
      in the majority of pituitary cells expressing ATP-gated receptor-channels are
      highly comparable to those observed in cells co-transfected with P2X2aR and
      P2X2bR. ATP-induced [Ca2+]i response in pituitary cells is partially inhibited by
      nifedipine, a blocker of voltage-gated L-type Ca2+ channels, suggesting that
      P2X2R not only drive Ca2+ into the cell, but also activate voltage-gated Ca2+
      entry. Our results indicate that ATP represents a paracrine and (or) autocrine
      factor in the regulation of Ca2+ signaling, and that its actions are mediated in
      part by heteropolymeric P2X2R.

PMID- 10949090
TI  - Adverse outcome of subsyndromal and syndromal levels of depressive symptom
      severity.

PMID- 10949089
TI  - Symptoms of depression as a prospective risk factor for stroke.
AB  - OBJECTIVE: The objective of this study was to assess baseline levels of
      depression as a risk factor for stroke among white and black men and women.
      METHODS: A population-based cohort of 6095 stroke-free white and black men and
      women aged 25 to 74 years in the NHANES I Epidemiologic Followup Study were
      followed for an average of 16 years to a maximum of 22 years. The association
      between stroke and baseline self-reported depressive symptomatology was analyzed
      using Cox proportional hazards models adjusting for baseline age, race, sex,
      education, smoking status, body mass index, alcohol use, nonrecreational physical
      activity, serum cholesterol level, history of diabetes, history of heart disease,
      and systolic blood pressure. Hospital records and death certificates were used to
      identify stroke cases; a total of 483 cases were identified. RESULTS: In age
      adjusted models for all persons, white men, white women, and black persons of
      both sexes, depression was predictive of stroke. In risk-adjusted models for all
      persons (relative risk (RR) = 1.73, 95% confidence interval (CI) = 1.30-2.31) and
      for white men (RR = 1.68, 95% CI = 1.02-2.75), depression remained predictive of
      stroke. For white women, depression (RR = 1.52, 95% CI = 0.97-2.38) reached
      borderline significance (p = .07). For black persons, depression (RR = 2.60, 95%
      CI = 1.40-4.80) demonstrated a higher risk of stroke. A series of supplemental
      analyses also supported the association between depression and stroke.
      CONCLUSIONS: Depression is predictive of stroke across all strata. This
      nationally representative study gives evidence of a prospective association
      between depression and stroke.

PMID- 10949091
TI  - Reported chronic insomnia is independent of poor sleep as measured by
      electroencephalography.
AB  - OBJECTIVE: Several behavioral, physiological, and subjective variables were
      examined in subjects reporting chronic insomnia (IN group) and subjects with no
      complaint of insomnia (NC group) to determine factors predictive of poor sleep as
      measured by electroencephalography (EEG sleep). METHODS: A total of 177 subjects
      (121 in the IN group and 56 in the NC group) were evaluated on the basis of EEG
      sleep, subjective sleep, sleepiness, performance, mood, personality, and
      metabolic parameters during a 36-hour laboratory stay. RESULTS: Equal percentages
      of subjects in each group had 0, 1, or 2 nights of poor EEG sleep, indicating
      that the IN group was not more likely to have impaired sleep in the laboratory.
      Results of the Minnesota Multiphasic Personality Inventory showed that subjects
      in the IN group had more pathological personality profiles, and results of
      laboratory studies showed that these subjects had worse mood ratings, less
      subjective sleepiness, poorer memory performance, and longer midafternoon sleep
      latencies. Subjects in the IN group also rated their laboratory sleep as poorer
      in quality with more time awake after sleep onset and longer sleep latencies, but
      no differences in EEG sleep were observed. Poor nights of EEG sleep were
      associated with being male, increasing age, and a history of more time awake
      after sleep onset; among the laboratory tests, poor EEG sleep was associated with
      worse mood ratings, poorer memory performance, longer sleep latencies (as
      indicated by higher scores on the Multiple Sleep Latency Test), higher sleep/wake
      ratios for metabolic parameters, lower ratings of sleep quality, and longer
      perceived sleep latencies. CONCLUSIONS: A history of chronic insomnia does not
      predict poor EEG sleep. Both chronic insomnia and poor EEG sleep are associated
      independently with dysphoria, hyperarousal, diminished waking function, and
      negative subjective sleep quality. Separate arousal and sleep systems are posited
      to account for these results.

PMID- 10949092
TI  - The nature of insomnia and the need to refine our diagnostic criteria.

PMID- 10949093
TI  - Alexithymia and impoverished dream content: evidence from rapid eye movement
      sleep awakenings.
AB  - OBJECTIVE: Despite the repeated suggestion in the literature of an association
      between impoverished dream processes and alexithymia, little systematic research
      has been conducted. METHODS: Eight nonclinical adults scoring in the alexithymia
      range and eight nonclinical adults scoring in the nonalexithymia range on a
      measure of alexithymia were awakened for dream reports during their second,
      third, and fourth rapid eye movement periods on the second of two consecutive
      polygraphically monitored nights in a sleep laboratory. RESULTS: The alexithymic
      and nonalexithymic groups did not differ in the number of dreams reported or the
      number of words used in the description of their dreams. The two groups also did
      not differ in their self-reports of the emotional valence associated with their
      dream experiences. In contrast, the dream reports of the alexithymic group were
      rated as less fantastic than the dream reports of the nonalexithymic group.
      CONCLUSIONS: These findings provide additional evidence that alexithymia involves
      restricted imaginative processes.

PMID- 10949094
TI  - Pervasive emotion recognition deficit common to alexithymia and the repressive
      coping style.
AB  - OBJECTIVE: Previous research has demonstrated a deficit in the ability to
      recognize emotions in alexithymic individuals. The repressive coping style is
      thought to preferentially impair the detection of unpleasant compared with
      pleasant emotions, and the degree of deficit is typically thought to be less
      severe than in alexithymia. We compared emotion recognition ability in both
      individuals with alexithymia and those with the repressive coping style. METHODS:
      Three hundred seventy-nine subjects completed the 20-item Toronto Alexithymia
      Scale, the Levels of Emotional Awareness Scale, the Marlowe-Crowne Scale (a
      measure of repressive defensiveness), the Bendig Short Form of the Taylor
      Manifest Anxiety Scale, and the Perception of Affect Task. The Perception of
      Affect Task consists of four 35-item emotion recognition subtasks: matching
      sentences and words, faces and words, sentences and faces, and faces and
      photographs of scenes. The stimuli in each subtask consist of seven emotions
      (happiness, sadness, anger, fear, disgust, surprise, and neutral) depicted five
      times each. Recognition accuracy results were collapsed across subtasks within
      each emotion category. RESULTS: Highly alexithymic subjects (for all, p<.01) and
      those with low emotional awareness (for all, p<.001) were consistently less
      accurate in emotion recognition in all seven categories. Highly defensive
      subjects (including repressors) were less accurate in the detection of anger,
      sadness, fear, and happiness (for all, p<.05). Furthermore, scores on the Levels
      of Emotional Awareness Scale accounted for significantly more variance in
      performance on the Perception of Affect Task than scores on the Marlowe-Crowne
      Scale (p<.01). CONCLUSIONS: The results indicate that alexithymia and the
      repressive coping style are each associated with impairments in the recognition
      of both pleasant and unpleasant emotions and that the two styles of emotional
      self-regulation differ more in the magnitude than in the quality of these
      impairments.

PMID- 10949095
TI  - Immune, endocrine, and psychological responses in civilians displaced by war.
AB  - OBJECTIVES: The objectives of this study were to assess the influence of trauma
      caused by forced expulsion from home in a war-ravaged region on the
      psychological, hormonal, and immune responses in displaced persons and to analyze
      the relationships between psychometric, hormonal, and immunologic variables.
      METHODS: Participants were 20 displaced and 14 control women. Psychosomatic
      response was evaluated using the COR-NEX2 test. Serum concentrations of cortisol,
      prolactin, endorphin, thyroxine, and triiodothyronine were measured by
      radioimmunoassay. Immunophenotyping and lymphocyte proliferation were determined
      by flow cytometry, and phagocyte functions (i.e., ingestion and antibody
      dependent cytotoxicity) against 51Cr-labeled sheep red blood cells were assessed
      through radioactivity uptake and release, respectively. RESULTS: In comparison
      with control women, displaced women had higher COR-NEX2 test scores; higher serum
      cortisol, prolactin, and endorphin levels; an increase in activated phenotype
      within all three measured cell populations (i.e., B, T, and natural killer
      cells); as well as an enhanced proportion of proliferating lymphocytes in freshly
      isolated samples. However, the phytohemagglutinin-stimulated proliferative
      response, estimated as the stimulation index, was lower in displaced women. A
      complex pattern of relations between psychological, hormonal, and immune
      responses was observed. CONCLUSIONS: Chronic psychological stress elicited
      multiple, predominantly stimulatory influences on immune functions.

PMID- 10949097
TI  - Race and sex differences in cutaneous pain perception.
AB  - OBJECTIVE: The purpose of this study was to determine race and sex differences in
      cutaneous pain perception. METHODS: Pain perception was measured using a
      suprathreshold evaluation of pain intensity and pain unpleasantness to a series
      of thermal stimuli in 27 whites (14 men and 13 women) and 24 African Americans
      (12 men and 12 women). Blood pressure, depressive symptoms, anxiety state levels,
      and negative mood were assessed before pain testing to examine whether they might
      account for any sex or race differences in pain perception that emerged. RESULTS:
      African Americans rated the stimuli as more unpleasant and showed a tendency to
      rate it as more intense than whites. Women showed a tendency to rate the stimuli
      as more unpleasant and more intense than men. In addition, systolic blood
      pressure was inversely related to pain intensity. After statistically adjusting
      for systolic blood pressure, sex differences in pain unpleasantness were reduced
      and sex differences in pain intensity were abolished; race differences were
      unaltered. CONCLUSIONS: These differences in pain perception may be associated
      with different pain mechanisms: in the ease of sex, differences in opioid
      activity and baroreceptor-regulated pain systems; in the case of race, unmeasured
      psychological characteristics are suggested by the larger differences in ratings
      of pain unpleasantness than pain intensity.

PMID- 10949096
TI  - Cardiovascular stress responses and their relation to symptoms in Gulf War
      veterans with fatiguing illness.
AB  - OBJECTIVE: The objective of this study was to examine whether inappropriate
      cardiovascular responses to stressors may underlie symptoms in Gulf War veterans
      with chronic fatigue. METHODS: Psychophysiological stress testing was performed
      on 51 Gulf War veterans with chronic fatigue (using the 1994 case definition of
      the Centers for Disease Control and Prevention) and 42 healthy veterans.
      Hemodynamic responses to cold pressor, speech, and arithmetic stressors were
      evaluated using impedance cardiography. RESULTS: Veterans with chronic fatigue
      had diminished blood pressure responses during cognitive (speech and arithmetic)
      stress tests due to unusually small increases in total peripheral resistance. The
      cold pressor test, however, evoked similar blood pressure responses in the
      chronic fatigue and control groups. Low reactivity to cognitive stressors was
      associated with greater fatigue ratings among ill veterans, whereas an opposite
      relation was observed among healthy veterans. Self-reported neurocognitive
      decline was associated with low reactivity to the arithmetic task. CONCLUSIONS:
      These results suggest a physiological basis for some Gulf War veterans' reports
      of severe chronic fatigue. A greater deficit with responses processed through
      cerebral centers, as compared with a sensory stimulus (cold pressor), suggests a
      defect in cortical control of cardiovascular function. More research is needed to
      determine the specific mechanisms through which the dissociation between
      behavioral and cardiovascular activities identified in this study may be
      contributing to symptoms in Gulf War veterans.

PMID- 10949098
TI  - Effects of relaxation and stress on the capsaicin-induced local inflammatory
      response.
AB  - OBJECTIVE: Although stress is known to modulate the inflammatory response, there
      has been little experimental examination of the effects of stress and stress
      reduction on inflammation in humans. In particular, the effects of stress and
      relaxation on neurogenic inflammation have been minimally studied. This study
      examines the effects of three experimental manipulations: mental stress,
      relaxation, and control on the local inflammatory response evoked by the
      intradermal injection of capsaicin, the active ingredient in chili peppers.
      METHODS: Fifty subjects (28 men and 22 women) were pretrained in relaxation using
      an imagery-based relaxation tape and then randomized to experimental condition.
      Subjects participated in an evening reactivity session including 20 minutes of a
      stress (Stroop test), relaxation (tape), or control (video) manipulation,
      followed by a capsaicin injection in the forearm. Digitized flare measurements
      were taken for 1 hour postcapsaicin, and measurements of cardiovascular
      variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken
      at regular intervals. RESULTS: The size of the maximum capsaicin-induced flare
      was significantly smaller in the relaxation condition than in the stress or
      control conditions, which did not differ from each other. Increases in
      norepinephrine, heart rate, and systolic blood pressure during the experimental
      task, but not after capsaicin, significantly predicted size of maximum flare and
      total area under the curve of flare measurements. CONCLUSIONS: These findings
      suggest that stress reduction may affect local inflammatory processes. Results
      are consistent with sympathetic modulation of the effects of relaxation on the
      flare response.

PMID- 10949099
TI  - Tryptophan levels, excessive exercise, and nutritional status in anorexia
      nervosa.
AB  - OBJECTIVE: It has been hypothesized that reduced dietary availability of
      tryptophan may be the cause of impaired serotonin activity in underweight
      anorexics. The study reported here evaluated the relationship between tryptophan
      availability in the blood and nutritional status in anorexia nervosa. METHODS:
      The total amount of tryptophan and the ratio between tryptophan and other large
      neutral amino acids (TRP/LNAA) were assessed in a sample of 16 starving anorexic
      patients. Body weight and composition and energy intake were evaluated in all
      patients. All subjects also completed self-reported questionnaires such as the
      Hopkins Symptom Checklist and Eating Disorders Inventory (EDI). RESULTS: The
      TRP/LNAA ratio seems to be higher in patients with a more severe catabolic
      status. It is, in fact, significantly inversely correlated with body mass index,
      body fat, muscle mass, daily energy intake, and daily tryptophan intake. The
      TRP/LNAA ratio also correlates with growth hormone and the EDI drive for
      thinness. Patients who exercise excessively had significantly higher TRP/LNAA
      ratios. CONCLUSIONS: In starving anorexic patients, the TRP/LNAA ratio does not
      seem to be determined by the content of tryptophan in the diet, but it correlates
      with measures of catabolism. The relationship of the TRP/LNAA ratio to excessive
      exercise and starvation indicates the importance of further investigations
      exploring the role of tryptophan availability in maintaining anorexia nervosa.

PMID- 10949100
TI  - Women with eating disorder tendencies display altered cardiovascular,
      neuroendocrine, and psychosocial profiles.
AB  - OBJECTIVE: Cardiovascular, neuroendocrine, and psychosocial profiles were
      investigated in women with eating disorder tendencies, but who had never met
      clinical criteria for an eating disorder, and in healthy controls. METHODS:
      Twenty-six women who scored in the highest distribution of the Eating Disorder
      Inventory bulimia subscale (HEDI women) and 27 women who scored in the lowest
      distribution (LEDI women) completed psychosocial questionnaires, underwent a
      speech reactivity task for measures of blood pressure and heart rate reactivity,
      and also underwent 24-hour ambulatory blood pressure monitoring and urinary
      neuroendocrine collection. RESULTS: The HEDI women exhibited increased blood
      pressure and heart rate reactivity to the speech task and increased 24-hour
      urinary cortisol, but decreased 24-hour urinary norepinephrine compared with LEDI
      women. There were no overall group differences in 24-hour ambulatory blood
      pressure levels, but negative mood and tension were associated with greater
      systolic blood pressures for all women. Finally, HEDI women reported greater
      depressive symptoms and anxiety, lower self-esteem and sense of mastery, less
      social support, poor coping skills, and greater emotional impact of daily
      stressors relative to LEDI women. CONCLUSIONS: These results indicate that the
      same pattern of neuroendocrine and psychosocial profiles seen in prior studies of
      bulimia nervosa are also present in women with eating disorder tendencies.

PMID- 10949101
TI  - Effects of yohimbine on cerebral blood flow, symptoms, and physiological
      functions in humans.
AB  - OBJECTIVE: Increases in adrenergic activity are associated with stress, anxiety,
      and other psychiatric, neurological, and medical disorders. To improve
      understanding of normal CNS adrenergic function, CBF responses to adrenergic
      stimulation were determined. METHODS: Using PET, the CBF changes after
      intravenous yohimbine, an alpha2-adrenoreceptor antagonist that produces
      adrenergic activation, were compared with placebo in nine healthy humans. Heart
      rate, blood pressure, Paco2, plasma catecholamines, and symptom responses were
      also determined. RESULTS: Among nonscan variables, yohimbine produced significant
      symptom increases (including a panic attack in one subject), a decrease in Paco2
      due to hyperventilation, increases in systolic and diastolic blood pressure, and
      a trend toward a significant norepinephrine increase. Among scan results,
      yohimbine produced a significant decrease in whole-brain absolute CBF; regional
      decreases were greatest in cortical areas. Medial frontal cortex, thalamus,
      insular cortex, and cerebellum showed significant increases after normalization
      to whole brain. Medial frontal CBF change was correlated with increases in
      anxiety. A panic attack produced an increase instead of a decrease in whole-brain
      CBF. Factors potentially contributing to the observed CBF changes were critically
      reviewed. Specific regional increases were most likely due in large part to
      activation produced by adrenergically induced anxiety and visceral symptoms.
      CONCLUSIONS: This study supports the relationship of anxiety and interoceptive
      processes with medial frontal, insular, and thalamic activation and provides a
      baseline for comparison of normal yohimbine-induced CNS adrenergic activation,
      adrenergically-based symptoms, and other markers of adrenergic function to
      stress, emotion, and the adrenergic pathophysiologies of various CNS-related
      disorders.

PMID- 10949102
TI  - Epstein-Barr virus antibodies in whole blood spots: a minimally invasive method
      for assessing an aspect of cell-mediated immunity.
AB  - OBJECTIVE: Study 1: Introduce and validate a method for measuring EBV p18-VCA
      antibodies in whole blood spots to provide a minimally invasive marker of cell
      mediated immune function. Study 2: Apply this method to a large community-based
      study of psychopathology in children and adolescents. METHODS: The EBV antibody
      method was evaluated through analysis of precision, reliability, stability, and
      comparisons with plasma and indirect immunofluorescence methods. The effects of
      life events on p18-VCA antibody level were considered in a subsample of 9, 11,
      and 13 year-old children participating in the Great Smoky Mountains Study in
      North Carolina. The subsample was stratified by age, sex, and degree of overall
      life strain. RESULTS: Dried blood spots provided a convenient, sensitive,
      precise, and reliable method for measuring EBV p18-VCA antibody titer. Life
      events were positively associated with p18-VCA antibodies in girls but not in
      boys. CONCLUSIONS: The validity of the blood spot EBV p18-VCA antibody assay, as
      well as the ease of sample collection, storage, and transportation, may provide
      an opportunity for psychoneuroimmunology to explore a wider range of stress
      models in larger, community-based studies.

PMID- 10949103
TI  - Influence of cholesterol and fasting insulin levels on blood pressure reactivity.
AB  - OBJECTIVE: This study examined how cholesterol and fasting insulin levels are
      related to blood pressure reactivity to behavioral stressors. METHODS: Subjects
      (N = 116) were 20 to 52 years old, at 80% to 150% of ideal weight, and had an
      average fasting cholesterol level of 183 mg/dl. Stressor tasks included mirror
      star tracing and a videotaped speech task. Changes from baseline were calculated
      for systolic and diastolic blood pressure. RESULTS: Neither cholesterol nor
      insulin was independently related to blood pressure change scores. However, after
      controlling for body mass, a two-way analysis of variance revealed a significant
      cholesterol-by-insulin interaction for change in diastolic blood pressure (p =
      .022). Subjects in the high-cholesterol/high-insulin group showed the greatest
      increase in diastolic blood pressure reactivity. CONCLUSIONS: In a general
      population, people with a below-average cholesterol level experience only
      moderate cardiovascular reactivity to mental stressors regardless of their
      fasting insulin level. However, for people with an above-average cholesterol
      level, fasting insulin level is an important factor in determining potential
      reactivity to mental stressors. These findings highlight the importance of
      adequate sample size to allow for the analysis of such interactions in future
      studies of cholesterol, insulin, and blood pressure reactivity.

PMID- 10949104
TI  - Effect of early body image dissatisfaction on subsequent psychological and
      physical adjustment after disfiguring injury.
AB  - OBJECTIVE: The impact of body image dissatisfaction on quality of life after
      severe burn injury was investigated after controlling for other determinants of
      outcome (i.e., injury, distress, and preburn quality of life). METHODS: The
      postburn quality of life (2-months postdischarge) of groups with and without body
      image dissatisfaction was studied after controlling for preburn quality of life
      (measured 2-3 days postadmission). The patient population (N = 86) was 77.9% men,
      had an average total body surface area burned of 17.02%, and average full
      thickness burn of 6.09%. Forty percent had facial injuries, 68.6% required
      surgery, most were injured by flame (39.5%), and 76.8% were employed. RESULTS:
      Multivariate analysis of covariance (covarying preburn level of Mental quality of
      life, facial injury, and size of burn) contrasting body image dissatisfaction
      groups found significantly lower psychosocial adjustment at 2-month follow-up in
      those with greater body image dissatisfaction (multivariate F = 3.61; p<.01). A
      second MANCOVA (covarying the preburn level of Physical quality of life and both
      facial injury and size of burn) found significantly lower physical functioning at
      2-month follow-up in those with greater body image dissatisfaction (multivariate
      F = 2.78; p < .03). Adding two more covariates (depression and posttrauma
      distress) eliminated the effect of body image dissatisfaction on postburn
      Physical but not Mental adjustment. CONCLUSIONS: Body image dissatisfaction
      affects quality of life after severe burn injury. Distress moderates this impact
      on aspects of physical but not psychosocial health.

PMID- 10949105
TI  - Human aggression and enumerative measures of immunity.
AB  - OBJECTIVE: A pattern of clinical, behavioral, and experimental findings suggests
      that individual differences in aggressive behavior may be related to immunologic
      processes. We evaluated two conflicting models of the relationship: 1) A positive
      association stems from an adaptive mechanism protecting aggressive individuals
      from increased exposure to immune stimuli and 2) a negative association is due to
      potential immunosuppressive effects of high testosterone levels. METHODS: We
      investigated the models using enumerative measures of cellular and humoral
      immunity in a sample of 4415 men aged 30 to 48 years who were interviewed and
      underwent a medical examination. RESULTS: Analysis revealed positive (and
      curvilinear) associations between aggressive behavior and enumerative measures of
      helper/inducer and suppressor/cytolytic T lymphocytes and B lymphocytes. The
      aggression-immunity relationship was independent of testosterone level, age,
      current health status, and negative health behaviors and was most pronounced for
      helper/inducer T cells. There was no evidence of a negative association between
      testosterone and any immune measure. CONCLUSIONS: In a large sample of men,
      individual differences in aggressive behavior were positively associated with
      enumerative measures of cellular immunity.

PMID- 10949106
TI  - Interleukin-6 and tumor necrosis factor-alpha production after acute
      psychological stress, exercise, and infused isoproterenol: differential effects
      and pathways.
AB  - OBJECTIVE: The aim of the study was to assess the effects of three different
      methods of acute activation of the sympathetic nervous system on
      lipopolysaccharide-induced in vitro production of interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha). METHODS: Thirty-two healthy volunteers
      performed speech and exercise tasks and underwent a 30-minute infusion of
      isoproterenol. RESULTS: As expected, acute activation of the sympathetic nervous
      system led to leukocytosis, including increases in lymphocyte, monocyte, and
      granulocyte populations (p values <.05). Lipopolysaccharide-induced IL-6
      production was increased after both the speaking and exercise tasks (p values
      <.001), whereas TNF-alpha production was elevated only after exercise (p<.05). In
      contrast, infusion of isoproterenol inhibited TNF-alpha production (p<.001) and
      caused no change in IL-6 production. CONCLUSIONS: In response to the challenges,
      IL-6 and TNF-alpha production showed different profiles. Purely beta-agonist
      stimulation led to downregulation of TNF-alpha production, providing evidence of
      the antiinflammatory effect of in vivo beta-receptor activation. The enhanced
      production of both cytokines after exercise, and of IL-6 after the speech task,
      can be best explained by a simultaneous upregulation of proinflammatory and
      inflammation-responding mediators. These effects may have an important role in
      controlling the immune response to acute psychological and physical stress.

PMID- 10949107
TI  - Nefazodone in diabetic neuropathy: response and biology.

PMID- 10949108
TI  - Angiotensin-(1-7). One step forward?
AB  - Angiotensin-(1-7) [Ang-(1-7)] is a paracrine hormone of the renin-angiotensin
      system (RAS). It counterbalances the negative actions of angiotensin II (Ang II)
      acting in the cardiovascular system, kidneys and central nervous system, and is
      responsible for blood pressure regulation and antiproliferative effects. Current
      data strongly suggest the existence of a specific receptor for this peptide. The
      concentration of Ang-(1-7) increases significantly during the administration of
      RAS blockers. One may suggest the involvement of this peptide in a beneficial
      effect of these drugs.

PMID- 10949109
TI  - Effect of repeated treatment with milnacipran on the central dopaminergic system.
AB  - Milnacipran (MIL) is a representative of a new class of antidepressants (SNRIs)
      which inhibit the reuptake of serotonin and noradrenaline, but, in contrast to
      tricyclics, show no affinity for neurotransmitters receptors. The present study
      was aimed at determining whether repeated MIL administration (given at doses of
      10 or 30 mg/kg, twice daily for 14 days) induced the adaptive changes in the
      dopaminergic system similar to those reported by us earlier for tricyclic
      antidepressants. The obtained results showed that MIL administered repeatedly did
      not change the responsiveness of dopamine D1 receptors since it did not change
      the SKF 38393-induced grooming. Repeated MIL treatment increased the
      hyperlocomotion induced by D-amphetamine and 7-OH-DPAT, but did not affect the D
      amphetamine and apomorphine stereotypies. The binding parameters (Bmax and Kd) to
      dopamine D1 and D2 receptors in the limbic forebrain were not affected by
      repeated MIL treatment when [3H]SCH 23390 and [3H]spiperone, respectively, were
      used as ligands. On the other hand, the increased density of dopamine D2
      receptors (Bmax) was observed in the striatum after repeated treatment with MIL.
      MIL administered acutely or repeatedly did not change the binding of [3H]7-OH
      DPAT to dopamine D3 receptors in the islands of Calleja and the shell region of
      the nucleus accumbens septi. The above results indicate that repeated MIL
      administration induces the adaptive changes in the dopaminergic system,
      especially it enhances the functional responsiveness of dopamine D2 and D3
      receptors. However, the question whether this increased functional responsiveness
      is important for the clinical antidepressant efficacy, remains open.

PMID- 10949110
TI  - Supraspinally mediated analgesic effect of antidepressant drugs.
AB  - Imipramine and amitriptyline, nonselective monoamine reuptake inhibitors,
      citalopram, selective serotonin reuptake inhibitor, and maprotiline, selective
      noradrenaline reuptake inhibitor, were tested after intracerebroventricular (icv)
      and intrathecal (it) administration in the rat writhing test to establish the
      role of the spinal and/or supraspinal structures in their effects. All drugs
      evoked dose-dependent analgesia after icv but not after it microinjections. The
      changes in the nociceptive behavior of rats pre-treated with antidepressants were
      not due to the non-specific influences of the drugs on the animals' gross
      behavior, as revealed by the open field test. The obtained results suggest that
      an antidepressant-induced analgesia mainly depends on the supraspinal effect with
      minor, if any, contribution from the spinal mechanisms.

PMID- 10949111
TI  - Effect of monoterpene derivative KP-19 on the pressor activity of catecholamines
      in rats.
AB  - The present study investigated the influence of KP-19, the propranolol analogue,
      bearing natural monoterpene moiety in its structure, on the blood pressure and
      respiration, the effect on the isolated heart rhythm disturbances induced by
      occlusion and reperfusion and on the pressor activity of catecholamines in
      normotensive rats.

PMID- 10949112
TI  - Repeated corticosterone administration increases excitatory effect of 5-HT4
      receptor agonist in the rat hippocampus.
AB  - The objective of the present study was to investigate whether repeated exposure
      of rats to high level of corticosterone affects responses of CA1 hippocampal
      cells to the 5-HT4 receptor agonist zacopride. To assess responsiveness of CA1
      neurons to zacopride we used extracellular recording of population spikes evoked
      in CA1 cells by the stimulation of the Schaffer/collateral-commissural pathway in
      hippocampal slices. Rats were treated with corticosterone for 7 days (10 mg/kg
      sc, twice daily), slices were prepared two days after the last treatment.
      Zacopride induced an increase in the amplitude of population spike and repeated
      corticosterone treatment enhanced this excitatory effect. It is concluded that
      repeated treatment with corticosterone increases the responsiveness of
      hippocampal CA1 neurons to the 5-HT4 receptor activation.

PMID- 10949113
TI  - Synergistic effect of amantadine and imipramine in the forced swimming test.
AB  - The obtained results indicate that joint administration of amantadine (a non
      competitive NMDA receptor antagonist) and imipramine induced antidepressant-like
      effect in the forced swimming test even at doses of both drugs which were
      ineffective when each of the drugs was used alone.

PMID- 10949114
TI  - Professor Jerzy Maj--the 50th anniversary of his scientific activity

PMID- 10949115
TI  - Effect of liposome molecular composition on its ability to carry drugs.
AB  - Liposomes have become a popular supramolecular structures used to deliver highly
      toxic drugs. In order to fulfill commercial handling requirements, the lipid-drug
      aggregate has to form stable and reproducible preparations. When applied as a
      therapeutic agent, its behavior must ensure proper drug distribution and well
      controlled release. The aggregate should have such properties built into its
      structure. Those properties depend mainly on aggregate's lipid composition and
      current external environmental conditions. It is not possible to precisely
      predict the behavior of the aggregate, since currently there are no theories
      sufficiently accurate to describe such complex structures. Nevertheless, some
      parameters of the lipid-drug aggregate can be elucidated based on simplistic semi
      empirical theories. The paper presents general outline of molecular shape
      approximation and the zone model for the lipid bilayer. These two approximations
      were used as a starting point in the discussion of the effects of various
      membrane modifications on global aggregate behavior, as well as their relevance
      to the ability to carry drugs.

PMID- 10949116
TI  - Role of corticotropin-releasing factor (CRF) in anxiety.
AB  - Apart from its regulatory role in release of adrenocorticotropic hormone (ACTH)
      and beta-endorphin, corticotropin-releasing factor (CRF) is implicated in
      behavioral functions. This review summarizes the present knowledge of the role of
      CRF in anxiety and discusses probable sites and receptors involved in the
      anxiogenic-like effect of CRF as well as possible interactions between the CRF
      system and other peptides. The role of the CRF system in human psychopathological
      conditions associated with anxiety is also reviewed. Based on the available
      literature, we suggest that the CRF system may interact with antianxiety drugs
      and that this interaction may be of importance in the development of anxiety
      induced by ethanol or cocaine withdrawal.

PMID- 10949117
TI  - Five exon 1 variants of mu opioid receptor and vulnerability to alcohol
      dependence.
AB  - The human mu opioid receptor (hMOR) gene is a prime candidate gene responsible
      for addictive disorders. The present association study tested the hypothesis that
      hMOR exon 1 variants elicit susceptibility to alcohol dependence. We have
      analyzed five nucleotide changes in exon 1 of the hMOR gene. Three of them are in
      the 5'untranslated region of exon 1 at positions -172G/T,-111C/T and -3 8C/A, the
      remaining two variants cause amino acid substitutions: +17C/T (Ala6Val) and
      +118A/G (Asn40Asp). Our population-based association study included 327 German
      alcohol-dependent subjects and 340 ethnically matched controls. The lack of an
      allelic association suggests that the analyzed hMOR exon 1 variants do not
      contribute a common and substantial effect to the genetically determined
      vulnerability of alcohol dependence.

PMID- 10949118
TI  - Effects of alpha-escin on histomorphometrical parameters of long bones in rats
      with experimental post-steroid osteopenia.
AB  - The excess of glucocorticosteroids leads to the development of osteopenia. A
      decreased bone formation rate and an increased bone resorption rate are observed.
      The aim of the present study was to investigate the effects of alpha-escin on the
      experimental prednisolone-induced osteopenia. The experiments were carried out on
      male Wistar rats with initial body weight of 240-310 g, divided into 4 groups (n
      = 6): Control, Alpha-escin, Prednisolone, Prednisolone + alpha-escin.
      Prednisolone (5 mg/kg im daily) and/or alpha-escin (100 mg/kg po daily) were
      administered for 28 days. Transverse cross-section surfaces of the cortical
      diaphysis and of the marrow cavity in the tibia, transverse growth, width of
      endosteal and periosteal osteoid, thickness of trabeculae and width of epiphyseal
      cartilage were examined. Prednisolone administration caused osteopenic changes in
      rat bones. Alpha-escin administered to the control rats did not exert
      statistically significant influence on the investigated bone parameters. Alpha
      escin administration to prednisolone-treated rats slightly reduced the
      unfavorable effects of prednisolone on width of periosteal and endosteal osteoid
      and periosteal transverse growth in the tibia.

PMID- 10949119
TI  - Topological potential of zwitterion analogues of cimetidine as H2 receptor
      antagonists.
AB  - Topological potential of zwitterionic analogues of cimetidine as H2 receptor
      antagonists have been investigated using a number of topological indices viz.
      molecular redundancy index (MRI), first order molecular connectivity index
      (1chiV) and rooted Wiener (Ww) and rooted Szeged (Szw) indices. The multiple
      regression analysis have indicated that the H2 receptor antagonist activities (
      logKB) can be modelled using indicator parameters. Most significant results were
      obtained when MRI was coupled with Ww as well as the indicator parameters (Ip1
      and Ip2).

PMID- 10949121
TI  - Professor Zdzislaw Kleinrok--the 50th anniversary of his scientific activity

PMID- 10949120
TI  - Synthesis and pharmacological characteristics of novel (Z)-3-arylidene-indolin
      2(1H)-ones: preliminary results.
AB  - New amide derivatives of 1-(m-chlorophenyl)piperazine, the 5-HT2A antagonists 3
      6, with moderate in vitro and in vivo activity were obtained by enlargement of
      the indolin-2(1H)-one core with 3-arylidene substituents.

PMID- 10949122
TI  - Seizures evoked by mitochondrial toxin, 3-nitropropionic acid: new mechanism of
      epileptogenesis?
AB  - A number of data concerning the central action of mitochondrial toxins,
      substances impairing mitochondrial synthesis of ATP and thus compromising
      cellular energy status, has emerged within last years. 3-Nitropropionic acid (3
      NPA) is an irreversible inhibitor of succinate dehydrogenase and mitochondrial
      complex II. The experimental administration of 3-NPA may lead to selective
      neuronal loss and chorea-like behavioral alterations but, as was recently shown,
      it also evokes clonic convulsions in rodents. The gathered data suggest that
      disturbed mitochondrial energy metabolism might initiate the chain of events
      culminating in seizure episode and that 3-NPA might become a useful tool in
      studying "mitochondrial" seizures. It has been hypothesized that the resistance
      to standard anticonvulsive therapy occurring among high proportion of epilepsy
      sufferers may result from the impairment of mitochondrial energy status due to
      either genetic predispositions or environmental influences.

PMID- 10949123
TI  - Effects of estrogens on seizures and neurotoxicity.
AB  - Estrogens have proepileptic properties both in humans and experimental animals.
      On the other hand, estrogens attenuate neuronal damage due to a variety of
      insults including hypoglycemia, oxidative agents, hypoxia and glutamate receptor
      agonists. Since excitatory amino acids play a key role both in seizures and
      neurotoxicity, their involvement in the mechanism of proepileptic and
      neuroprotective effects of estrogens deserves special attention. In this short
      paper, some facts and hypotheses on genomic and nongenomic actions of estrogens
      on glutamate receptor-dependent seizures and neurotoxicity will be presented.

PMID- 10949124
TI  - Pilocarpine-induced seizures in rodents--17 years on.
AB  - In 1983, we reported that intracerebral or systemic administration of cholinergic
      agents produced seizures and seizure-related brain damage in rodents. During the
      following 17 years, seizures induced by cholinomimetic drugs became a popular
      model of epilepsy. Seizures can by produced by cholinergic agonists acting
      directly at muscarinic receptors or by drugs enhancing cholinergic transmission
      due to the inhibition of acetylcholinesterase activity. Status epilepticus evoked
      by pilocarpine in rodents triggers long-lasting changes which can be described
      as: (I) acute-onset seizures lasting for several hours, (II) a silent period
      characterized by normalization of electroencephalographic patterns lasting for
      days, and (III) spontaneous recurrent seizures lasting for life. Therefore,
      seizures induced by cholinomimetics in rodents are of value for studies of basic
      mechanisms of epileptogenesis and action of antiepileptic drugs.

PMID- 10949125
TI  - Perspectives for the use of excitatory amino acid ionotropic receptor antagonists
      as antiepileptic drugs.
AB  - Numerous antagonists of glutamate, belonging to N-methyl-D-aspartate (NMDA) and
      non-NMDA receptor antagonists, were demonstrated to display anticonvulsant
      activity in various models of experimental epilepsy. Also, the glutamate
      antagonists enhanced the protective activity of conventional antiepileptic drugs
      against maximal electroshock-induced seizures in mice. However, some combinations
      of conventional antiepileptics with NMDA receptor antagonists resulted in
      profound adverse effects. In contrast, the antagonists for the non-NMDA receptor
      group potentiated the anticonvulsant activity of conventional antiepileptics,
      with no side-effects being observed. In some cases, the combined treatments were
      superior to the administration of an antiepileptic drugs alone, as regards
      adverse effects. In no case, glutamate antagonists affected the plasma levels of
      antiepileptic drugs. These data seem to indicate that non-NMDA receptor
      antagonists bear more important clinical potential as adjuvant antiepileptic
      drugs.

PMID- 10949126
TI  - Thermosensitivity of multidrug-resistant human gastric and pancreatic carcinoma
      cells.
AB  - Often, tumour cells acquire drug resistance phenotypes, which include the
      classical multidrug resistance (MDR) phenomenon accompanied by the synthesis of
      the P-glycoprotein (Pgp) and atypical MDR phenotypes mediated by different, in
      part unknown, mechanisms. To investigate the susceptibility of tumour cells
      exhibiting different kinds of MDR to treatment with heat, the hyperthermic
      survival of established human gastric and pancreatic carcinoma cell lines were
      studied and sublines exhibiting a classical and an atypical MDR phenotype were
      derived, respectively. Arrhenius analysis of this panel of gastrointestinal
      tumour cells revealed that both the classical and the atypical MDR variants
      exhibited no breaking points (T*) in contrast to the parent tumour cells. The
      activation enthalpies E(A) were about 40% lower at T > T* in comparison to the
      E(A) at lower temperatures. Classical MDR variants of both gastrointestinal
      tumour cell types exhibited a similar E(A) value, whereas the E(A) of atypical
      MDR gastric carcinoma cells was 1.6-fold higher than the E(A) of corresponding
      pancreatic carcinoma cells. In comparison to the parent lines, the drug resistant
      variants exhibited a 2.1-fold (gastric carcinoma, classical MDR), 2.7-fold
      (gastric carcinoma, atypical MDR) and 1.4-fold (pancreatic carcinoma, classical
      MDR) increase of activation enthalpies and a nearby unchanged E(A) in pancreatic
      carcinoma cells exhibiting an atypical MDR.

PMID- 10949127
TI  - Heat shock response by cells treated with azetidine-2-carboxylic acid.
AB  - The purpose of this study is to reinvestigate the heat shock response in cells
      treated with the antimetabolite azetidine-2-carboxylic acid (azetidine), an
      analogue of proline. Previous studies could not clearly discriminate between the
      progressive thermosensitization caused by amino acid analogues and a parallel
      induction of thermotolerance by heat shock. Incubation of H35 cells with 2.5 mm
      azetidine causes an increasing thermosensitization which achieves a maximum after
      approximately 18-22 h. At this point, azetidine does not prevent the development
      of acute thermotolerance following a heat shock at 42.5 degrees C, or the
      simultaneous induction of chronic thermotolerance during mild hyperthermia at 38
      41 degrees C. However, for both the acute and chronic heating conditions
      thermotolerance levels are reduced in proportion with azetidine
      thermosensitization. Incorporation of azetidine causes an apparent downward
      temperature shift of approximately 1 degree C relative to the time-temperature
      relationships for normal, or following heat shocks, for thermotolerant cells.
      After 18 h of incubation with azetidine, protein synthesis is reduced by a factor
      of 4 and cells show a preferential synthesis of heat shock proteins (hsp). A heat
      shock then, although inducing thermotolerance, is not followed by any noticeable
      effect on the synthesis of hsps. It is shown that the combination of prolonged
      azetidine treatment and heat shock causes a persistent inhibition of protein
      synthesis. This is hypothesized to result in the development of hsp synthesis
      independent thermotolerance. Additional treatment following heat shock in
      azetidine-treated cells with the protein synthesis inhibitor cycloheximide does
      not affect the induction of thermotolerance. In contrast to the heat shock
      response, no thermotolerance induction is observed in azetidine-treated cells
      after an exposure to sodium arsenite.

PMID- 10949128
TI  - Cystosarcoma phyllodes malignum: a case report of a successive triple modality
      treatment.
AB  - This paper reports on a woman with a rapidly growing recurrent cystosarcoma
      phyllodes malignum after two major attempts of surgery. In this situation,
      neoadjuvant hyperfractionated radiotherapy, superficial hyperthermia and
      ifosfamide were administered. Toxicity was mild. Resection of the tumour bed
      revealed a pathologically complete response with an actual disease free follow-up
      of 48 months.

PMID- 10949129
TI  - Feasibility and analysis of thermal parameters for the whole-body-hyperthermia
      system IRATHERM-2000.
AB  - The infrared system IRATHERM-2000, with water-filtered infrared A wavelength
      underwent 20 treatments of whole body hyperthermia in conjunction with
      chemotherapy. In all the sessions, the aimed systemic temperature (41.8 degrees
      C, maximum 42.0 degrees C) could be achieved and maintained for 60 min. Due to
      increasing clinical experience, the unnegligible local toxicity, exhibited as
      heat-induced superficial lesions, and neurotoxicity, could be reduced during the
      course of the study. Data from three other series accomplished at the von Ardenne
      Clinic, totalling 120 heat sessions, were available and included for a
      comparative analysis. Analysis of the toxicity shows that a correlation exists
      between thermal side-effects and heat-up periods (until steady-state), maximum
      temperatures, and superficial thermal doses. The time needed to reach the plateau
      seems to correlate with fluid loss, which, thus, indirectly influences toxicity,
      and most importantly the initial power level. The typical heat-up time in such a
      standard set-up amounts to 100-150 min, for a temperature rise from 37.5 to 42.0
      degrees C. Evaluation of the energy balance reveals a highly patient-specific
      range for the reactive evaporation in the IRATHERM system, resulting in a power
      (heat) loss of up to 1400 W via sweat production of approximately 2 l/h. In order
      to counterbalance this effect, an accordingly high infrared power, ranging from
      1200-1500 W, needs to be delivered, resulting in a significant thermal skin
      exposition. Concepts used to reduce the heat loss by reactive evaporation include
      prevention of convection by appropriate sealing of the heating chamber and
      increasing the humidity by a nebulizer. For the more trained user, the heat-up
      time can be considerably shortened, particularly, in the introductory phase of
      the heating process, by employing higher, but still tolerable, patient-specific
      power levels. However, such a strategy requires, due to higher risks, close
      monitoring of skin temperatures together with a considerable amount of clinical
      experience. The results of the IRATHERM pilot study were compared, not only with
      previous groups where the IRATHERM was applied, but also with results of various
      other investigators where the Enthermics Radiant Heat Device was employed. In the
      authors' opinion, improved understanding of the mechanisms and crucial parameters
      underlying whole body hyperthermia, will enable a controllable and tolerable
      therapy through proficient contribution to equipment and methods.

PMID- 10949130
TI  - Hybrid finite element-finite difference method for thermal analysis of blood
      vessels.
AB  - A hybrid finite-difference/finite-element technique for the thermal analysis of
      blood vessels embedded in perfused tissue has been developed and evaluated. This
      method provides efficient and accurate solutions to the conjugated heat transfer
      problem of convection by blood coupled to conduction in the tissue. The technique
      uses a previously developed 3D automatic meshing method for creating a finite
      element mesh in the tissue surrounding the vessels, coupled iteratively with a 1
      D marching finite difference method for the interior of the vessels. This hybrid
      technique retains the flexibility and ease of automated finite-element meshing
      techniques for modelling the complex geometry of blood vessels and irregularly
      shaped tissues, and speeds the solution time by using a simple finite-difference
      method to calculate the bulk mean temperatures within all blood vessels. The use
      of the 1D finite-difference technique in the blood vessels also eliminates the
      large computer memory requirements needed to accurately solve large vessel
      network problems when fine FE meshes are used in the interior of vessels. The
      accuracy of the hybrid technique has been verified against previously verified
      numerical solutions. In summary, the hybrid technique combines the accuracy and
      flexibility found in automated finite-element techniques, with the speed and
      reduction of computational memory requirements associated with the 1D finite
      difference technique, something which has not been done before. This method,
      thus, has the potential to provide accurate, flexible and relatively fast
      solutions for the thermal analysis of coupled perfusion/blood vessel problems,
      and large vessel network problems.

PMID- 10949131
TI  - An on-line phase measurement system for quality assurance of the BSD 2000. Part
      I: technical description of the measurement system.
AB  - The hyperthermia system BSD 2000 with the ring applicator Sigma 60 utilizes the
      principle of a phase controlled group radiation source. The accuracy of the phase
      relationship between the four receiving HF signals is crucial for the position of
      the electric field inside the applicator. Therefore, essential significance falls
      to the phase control of the system. An automatic phase measuring technique has
      been developed to register immediately the phase position of the four channels of
      the BSD 2000 with respect to a reference signal. The system improves the
      insurance of the technical safeguarding. In the first part of this work, the
      technical realization of the measurement system is described and first
      measurements with the system are given. In the second part, results with respect
      to the quality assurance of the BSD 2000 system are presented.

PMID- 10949132
TI  - An on-line phase measurement system for quality assurance of the BSD 2000. Part
      II: results of the phase measurement system.
AB  - Phase constancy and accuracy are significant for regional hyperthermia with
      phased array radiofrequency hyperthermia systems. They are both necessary for a
      precise target steering in therapy. For the BSD 2000 system (BSD Medical Corp.
      Salt Lake City, Utah, USA), the phase values of all channels are checked with a
      self-developed automatic on-line phase measurement system. On different days the
      phases are measured under identical conditions, where the output paths are cut
      off with 50 ohm dummy loads to suppress the influence of the radiation conditions
      of the antennae on the measurement values. The results show how the phase values
      of the four channels change in the first 30 min and from day to day. During this
      time interval after the start the phases drop down by up to 15 degrees. For the
      time later changes are very slight and the differences from day to day are
      negligible. The phase shift that occurs in the first 30 min is as high as a
      change of the target point by 1 cm. Earlier switching on of the amplifiers
      prevents this shift occurring during the treatment. The measurement system
      provides a good tool for determination of phase accuracy and is easy to realize.

PMID- 10949133
TI  - Mix-mode technique of feeding arrays of dipole microwave antennae.
AB  - A 4-element array of coherently driven dipole microwave antennae produces a hot
      spot in the central region of the implanted volume and cold spots in the
      peripheral regions of the implant. Conversely, an incoherently driven array of
      antennae predominantly heats peripheral (along the antennae) regions of the
      implant. These two modes of feeding the antennae are complementary in a sense
      that the cold zones obtained with the coherently driven antennae coincide with
      the hot zones obtained with the incoherently driven antennae and vice versa. The
      SAR distributions resulting from mixing these modes of feeding (mixed-mode
      technique) were studied theoretically and experimentally. A theoretical model
      that allowed calculation of SAR distributions of a 4-element array of microwave
      antennae fed coherently, incoherently or using a mixed-mode technique was
      developed in this work. The goal of the theoretical study was to determine the
      proper mix of the coherent and incoherent modes of feeding the antennae such that
      the adequately (enclosed within a 50% isoSAR surface) heated volume was
      maximized. In experimental studies, the antennae were driven in a cyclical manner
      with a duty cycle equal to the weight of the coherent mode in the mix. The duty
      cycle was defined as the ratio of the time the antennae were driven coherently to
      the total duration of the cycle. To facilitate the periodical change from the
      coherent to incoherent feeding, a special electromechanical switch was developed.
      This switch allowed a wide range of variation of the duty cycle and cycle period.
      Theoretical and experimental studies have demonstrated that, if the relative
      weight of the coherent feeding in the mix-mode technique was 30% (duty cycle =
      0.3), the adequately heated volume was significantly larger and the SAR
      distribution was more uniform than those obtained with either the coherent or
      incoherent mode of feeding.

PMID- 10949134
TI  - Enrichment of hydrophobic proteins via Triton X-114 phase partitioning and
      hydroxyapatite column chromatography for mass spectrometry.
AB  - Membrane proteins are the starting point of several signal transduction pathways.
      Therefore, the separation and identification of these proteins are of great
      interest in proteome analysis. However, the specific properties of membrane
      proteins seriously impede their analysis. We present an effective and highly
      reproducible method for the two-dimensional separation of extremely hydrophobic
      proteins and demonstrate the advantages of special preseparation procedures for
      the identification of proteins which have very similar Mr and p/. Using the
      example of the integral membrane protein very low density lipoprotein (VLDL)
      receptor (NCBI Acc. # 1730111) and the soluble heat shock protein (HSP) 90 (NCBI
      Acc. # 386786) we present the applicability of a phase-separation system with
      Triton X-114. Using matrix assisted laser desorption/ionization-time of flight
      mass spectrometry (MALDI-TOF-MS) of the protein spots after 2-D separation of the
      hydrophilic and the strongly hydrophobic protein fraction of human endothelial
      cells (ECV cell line), we were able to distinguish both proteins.

PMID- 10949135
TI  - Improved sensitivity proteomics by postharvest alkylation and radioactive
      labelling of proteins.
AB  - We describe approaches to improve the detection of proteins by postharvest
      alkylation and subsequent radioactive labeling with either [3H]iodoacetamide or
      125I. Database protein sequence analysis suggested that cysteine is not suitable
      for detection of the entire proteome, but that cysteine alkylating reagents can
      increase the number of proteins able to be detected by iodination chemistry.
      Proteins were alkylated with beta-(4-hydroxyphenyl)ethyl iodoacetamide, or with
      1,5-l-AEDANS (the Hudson Weber reagent). Subsequent iodination using the Iodo-Gen
      system was found to be most efficient. The enhanced sensitivity obtainable by
      using these approaches is expected to be sufficient for visualization of the
      lowest copy number proteins from human cells, such as from clinical samples.
      However, we argue that significantly improved methods of protein separation will
      be necessary to resolve the large number of proteins expected to be detectable
      with this sensitivity.

PMID- 10949136
TI  - In vitro coupled transcription translation: effects of modification in lysate
      preparation on protein composition and biosynthesis activity.
AB  - Cell-free extracts (lysates) from Escherichia coli were used for protein
      synthesis in vitro. Essential steps of the lysate preparation were modified and
      analyzed with respect to their impact on in vitro protein synthesis capacity,
      using the green fluorescent protein (GFP) as a target protein. Variably
      manufactured lysates of low, medium and higher protein synthesis activity, were
      examined by high resolution two-dimensional gel electrophoresis to determine
      whether the modifications result in substantial alterations in protein
      composition of the final lysate. The total number of proteins calculated from the
      gel maps did not vary for lysates with different activity and thus cannot serve
      as an evaluation parameter. Ribosomal proteins RP-S1, RP-L9, and RP-L10 were
      found in stoichiometric amounts for each of these lysates and in equal
      concentrations in comparison among the different lysates. Conversely, depending
      on the activity profiles, up to 7 different isoforms of the elongation factor EF
      Ts were detected in the gel maps.

PMID- 10949137
TI  - Towards higher resolution: two-dimensional electrophoresis of Saccharomyces
      cerevisiae proteins using overlapping narrow immobilized pH gradients.
AB  - The rising number of proteome projects leads to new challenges for two
      dimensional electrophoresis with immobilized pH gradients and different
      applications of this technique. Not only wide pH gradients such as 4-12 or 3-12
      (Gorg et al., Electrophoresis 1999, 20, 712-717) which can give an overview of
      the total protein expressions of cells are in demand but also overlapping narrow
      immobilized pH gradients are to be used for more specialized and detailed
      research and micropreparative separations. The advantage of overlapping narrow pH
      gradients is the gain in higher resolution by stretching the protein pattern in
      the first dimension. This simplifies computer-aided image analysis and protein
      identification (e.g., by mass spectrometry). In this study the protein patterns
      of yeast cells in pH gradients 4-5, 4.5-5.5, 5-6, 5.5-6.7 and 6-9 are presented
      and compared to the pH 4-7 and 3-10 gradients. This combination allowed us to
      reveal a total of 2286 yeast protein spots compared to 755 protein spots in the
      pH 3-10 gradient.

PMID- 10949138
TI  - Towards high performance two-dimensional gel electrophoresis using ultrazoom
      gels.
AB  - Proteomics is the analysis of protein expression in cells or tissues, e.g., to
      study cellular processes at the molecular level. Ultimately, a proteome analysis
      should encompass most if not all protein species in a biological sample,
      including those present in low copy numbers. We are developing two-dimensional
      gel electrophoresis technology by applying narrow pH range ultrazoom gels to
      enhance resolution and to improve the detection of low abundance proteins.
      Ultrazoom gels in the acidic pH range allow the detection of proteins down to 300
      copies per cell of a B-lymphoma cell line. Protein separation in the alkaline pH
      range, however, still requires optimization, especially in conjunction with high
      sample loads.

PMID- 10949139
TI  - Identification of platelet proteins separated by two-dimensional gel
      electrophoresis and analyzed by matrix assisted laser desorption/ionization-time
      of flight-mass spectrometry and detection of tyrosine-phosphorylated proteins.
AB  - Different search programs were compared to judge their particular efficiency in
      protein identification. We established a human blood platelet protein map and
      identified tyrosine-phosphorylated proteins. The cytosolic fraction of human
      blood platelets was separated by two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE) and phosphorylated proteins were detected by Western
      blotting using anti-phosphotyrosine antibodies. Visualized protein spots were
      excised, digested with trypsin and analyzed by matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The
      obtained mass fingerprint data sets have been analyzed using ProFound, MS-Fit and
      Mascot. For those protein spots with no significant search results MALDI post
      source decay (PSD) spectra have been acquired on the same sample. For automatic
      interpretation of these fragment ion spectra, the SEQUEST and Mascot algorithm
      were applied. Another approach for the identification of phosphorylated proteins
      is immunoprecipitation using an anti-phosphotyrosine antibody. A method for
      immunoprecipitation of tyrosine-phosphorylated peptides was optimized.

PMID- 10949140
TI  - An alternative approach to deal with geometric uncertainties in computer analysis
      of two-dimensional electrophoresis gels.
AB  - With the growing importance of proteomics in biomedical and pharmaceutical
      sciences a need has emerged for computing tools that are capable of digitally
      visualizing and analyzing protein spot patterns within two-dimensional
      electrophoresis (2-DE) gel. Matching programs need to meet requirements such as
      interlaboratory comparison and the comparison of samples from different origins.
      For such research purposes, we have developed the CAROL system that implements
      new algorithms for spot detection and matching, which enable researchers to take
      a different approach to protein spot identification and comparison. The present
      short communication discusses how the system deals with uncertain geometric spot
      information that arises from streaks and complex spot regions and how this can be
      amplified for the matching procedure.

PMID- 10949141
TI  - A microarray enzyme-linked immunosorbent assay for autoimmune diagnostics.
AB  - In order to quantify autoantibodies in the sera of patients with autoimmune
      disease, we have created a microarray-based immunoassay that allows the
      simultaneous analysis of 18 known autoantigens. The microarrays contain serial
      dilutions of the various antigens, thereby allowing accurate determination of
      autoantibody titer using minimal amounts of serum. The assay is very sensitive
      and highly specific: as little as 40 fg of a known protein standard can be
      detected with little or no cross-reactivity to nonspecific proteins. The signal
      intensities observed from serial dilutions of immobilized antigen correlate well
      with serial dilutions of autoimmune sera. Miniaturized and highly parallelized
      immunoassays like these will reduce costs by decreasing reagent consumption and
      improve efficiency by greatly increasing the number of assays that can be
      performed with a single serum sample. This system will significantly facilitate
      and accelerate the diagnostics of autoimmune diseases and can be adapted easily
      to any other kind of immunoassay.

PMID- 10949142
TI  - Cross-species identification of novel Candida albicans immunogenic proteins by
      combination of two-dimensional polyacrylamide gel electrophoresis and mass
      spectrometry.
AB  - We have previously reported the usefulness of two-dimensional gel electrophoresis
      followed by Western blotting with sera from patients with systemic candidiasis in
      the detection of the major Candida albicans antigens (Pitarch et al.,
      Electrophoresis 1999, 20, 1001-1010). The identification of these antigens would
      be useful for the characterization of good markers for the disease, and for the
      development of efficient diagnostic strategies. In this work we have used
      nanoelectrospray tandem mass spectrometry to obtain amino acid sequence
      information from the immunogenic proteins previously detected. We report here the
      cross-species identification of these antigens by matching of tandem mass
      spectrometry data to Saccharomyces cerevisiae proteins. Using this approach, we
      unambiguously identified the four C. albicans immunogenic proteins analyzed,
      namely aconitase, pyruvate kinase, phosphoglycerate mutase and methionine
      synthase. Furthermore, we report for the first time that aconitase, methionine
      synthase and phosphoglycerate mutase have antigenic properties in C. albicans.

PMID- 10949144
TI  - Two-dimensional electrophoretic and immunoblot analysis of cell surface proteins
      of spiral-shaped and coccoid forms of Helicobacter pylori.
AB  - Cell surface proteins of the human gastric pathogen Helicobacter pylori extracted
      during different in vitro growth phases were analyzed by one- and two-dimensional
      gelelectrophoresis (1-DE and 2-DE) and by 2-DE immunoblot. Broth-cultured H.
      pylori cells were stained with an acridine-orange dye to monitor the
      morphological status of the organism. In 2-day-cultures, 96% of the bacterial
      cells were spiral-shaped and four days later a morphological switch to coccoid
      forms occurred. In 10-day cultures spiral-shaped forms were not found. By 1-DE,
      proteins with the molecular masses of 87 and 120 kDa were detected in the 2-day
      cultures that disappeared in cells of 12-day cultures. A protein corresponding in
      size to the heat shock protein (GroEl homolog, Hsp60) and a 62 kDa protein, the
      ureaseB-subunit, were identified in extracted proteins of 2-, 8-, and 12-day
      cultures. 2-DE revealed an increased number of silver-stained spots of 8-day
      cultures (in average 250 spots) compared with protein extracted from 2-day cells
      (in average 160 spots). 2-DE immunoblots performed with sera containing
      antibodies to major H. pylori proteins such as the A- and B-subunits of urease
      and the Hsp60 showed similar reactivity to surface proteins extracted from 2-, 8
      , and 12-day cultures, suggesting that these proteins remain immunologically
      intact. Pooled sera from infected patients absorbed with spiral-shaped cells
      showed an almost total blocking of the antibody reactivity to extracted coccoid
      proteins in 2-DE immunoblot. Eighteen spots were still visible, but this
      reactivity probably represents a solid overexpression by the coccoid cells of
      Hsp60 and ureaseB proteins and is thus difficult to block.

PMID- 10949143
TI  - "Early" protein synthesis of Lactobacillus delbrueckii ssp. bulgaricus in milk
      revealed by [35S] methionine labeling and two-dimensional gel electrophoresis.
AB  - The proteomes of exponentially growing and stationary cells of Lactobacillus
      delbrueckii ssp. bulgaricus grown in rich medium (MRS) were separated by two
      dimensional polyacrylamide gel electrophoresis (2-DE) and quantified after
      Coomassie staining. Stationary cells grown in MRS were inoculated in
      reconstituted skim milk, and "early" protein synthesis during the first 30 min of
      fermentation in milk was monitored by [35S]methionine labeling and 2-DE. In
      contrast to exponentially growing or stationary cells, the predominant "early"
      proteins were small (< 15 kDa) and of low pI (< 5.3). Quantification of the
      proteome of the "early" lag phase based on 47 "spots" revealed that only three
      "early" proteins accounted for more than 80% of the total label. They were
      identified as pI 4.7 and 4.9 isoforms of the heat-stable phosphoryl carrier
      protein (HPr) with 45.2 and 9.4% of total label, respectively, and an unknown
      protein called EPr1 ("early" protein 1) with 26.6% of total label. Although an N
      terminal sequence of 19 amino acids was obtained, no homologs to EPr1 could be
      found. De novo synthesis of the 10 and 60 kDa heat shock proteins (GroES and
      GroEL) was considerably lower (0.04 and 0.9% of total label, respectively),
      indicating only low levels of stress. Synthesis of triosephosphate isomerase
      (Tpi) as marker for glycolytic enzymes reached only 0.08% of total label. Our
      results demonstrate that inoculation in milk, resulting in a change from glucose
      to lactose as carbon source, imposes only little need for synthesis of stress or
      glycolytic enzymes, as sufficient proteins are present in the stationary, MRS
      grown cells. The high level of expression of the pI 4.7 isoform of HPr suggests a
      regulatory function of the presumed Ser-46 phosphorylated form of HPr.

PMID- 10949145
TI  - Identification of peanut and hazelnut allergens by native two-dimensional gel
      electrophoresis.
AB  - A procedure for the native two-dimensional electrophoresis of peanut and hazelnut
      proteins is described. Proteins were solubilised after acetone treatment using a
      combination of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)
      and tetramethylene sulphone. These extracts were analysed by a combination of
      isoelectric focusing in the presence of lactose in immobilized pH gradients
      followed by charge shift electrophoresis. Immunoblot analysis, using sera from
      nut allergic patients, allowed the identification of a peanut and hazelnut
      allergen with identical isoelectric point and apparent molecular mass. These
      proteins were recovered from duplicate gels using a mixture of formic acid,
      acetonitrile (ACN) and isopropanol. The molecular masses for both proteins,
      determined by matrix assisted laser desorption/ionisation-mass spectrometry
      (MALDI-MS), were 4826 Da.

PMID- 10949146
TI  - Protein kinase C alpha-dependent phosphorylation of Golgi proteins.
AB  - Golgi-enriched membranes were phosphorylated in order to understand the mechanism
      for protein kinase C (PKC) regulation of exocytic vesicle formation at the trans
      Golgi network. Two of the main PKC substrates were identified as MARCKS and Mac
      MARCKS by two-dimensional electrophoresis (2-DE) and mass spectrometric
      sequencing. Annexin IV and profilin I, two other Golgi-associated proteins-
      although known as in vitro PKC substrates--were not phosphorylated in the Golgi
      bound state.

PMID- 10949147
TI  - Global analysis of gene expression in cells of the immune system I. Analytical
      limitations in obtaining sequence information on polypeptides in two-dimensional
      gel spots.
AB  - We have outlined various aspects and limitations of the collective analysis of
      protein species of a cell (lymphocyte). We have indicated research directions
      that, in to our opinion, deserve more attention. We have evaluated mainly the
      approach used in our laboratory and we recognize that a bulk of important
      research on the interface of proteomics and genomics remains to be dealt with. It
      is of great value that we can proceed in our quest by trial and error. But as
      much as the human genome initiative was not implemented by trial and error, but
      by formulating new technological approaches, we hope that our approach can be
      incorporated in the mainstream of proteomics. We need several integrating
      research directions, some of which are outlined in this communication, namely the
      use of ordered cDNA libraries, cell-free expression systems, high density filter
      hybridization, identification of two-dimensional (2-D) gel spots in terms of
      their amino acid composition through biosynthetic labeling and identification of
      restriction sites in the corresponding coding sequences. In the accompanying
      paper the cDNA ordered library approach will be described in some detail.

PMID- 10949148
TI  - Global analysis of gene expression in cells of the immune system II. Cell-free
      translation products and high-density filter hybridization data.
AB  - We have developed an experimental system for linking information on cell-free
      transcription and translation products from cDNA clones with data obtained from
      hybridization signals from complex probes. The work described in this paper
      consists of two distinct processes, one being the construction of a system of
      clonal addresses and the other the identification of expressed genes involved in
      the studied processes. We describe the use of this system to identify genes
      involved in thymus development. Complex probes from fetal thymuses (GD15, 17 and
      newborn) of Balb/c mice were used to identify genes, which are up- or
      downregulated during the process of differentiation. The full set of information
      is available in the Clone-base of the Basel Institute for Immunology and will be
      retrievable from the website of the collaborating laboratories.

PMID- 10949149
TI  - Human bronchoalveolar lavage fluid protein two-dimensional database: study of
      interstitial lung diseases.
AB  - Recently, we published an analytical two-dimensional electrophoresis (2-DE)
      protein map of human bronchoalveolar lavage fluid (BALF) using a pool of BALFs
      from various patients. In this report, the effect of lung disorders on the
      protein composition of the lung epithelial lining fluid was investigated by 2-DE
      of BALFs from individual patients with well-defined interstitial lung diseases:
      sarcoidosis, idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis
      (HP), using improved experimental conditions. On these gels, about 600-1000
      stained protein spots could be identified in a BALF sample containing 25 microg
      of protein, and our original human BALF protein database has, therefore, been
      considerably extended. Altogether, 429 protein spots corresponding to 66
      different proteins (including isoforms, protein subunits and fragments) were
      identified by microsequence analysis and by matching with a human blood plasma 2
      DE protein map available in the SWISS-2DPAGE database. A human 2-DE BALF database
      was established and is available on the World Wide Web (http://www.umh.ac.be/
      biochim/proteomic.htm+ ++). The significance of the modifications observed
      between the different lung pathologies is discussed with the aim of understanding
      the mechanistic bases of lung disease pathogenesis and finding new potential lung
      markers of disorders.

PMID- 10949150
TI  - A two dimensional electrophoresis database of a human Jurkat T-cell line.
AB  - About 2000 protein spots of human Jurkat T-cells were detected by high resolution
      two-dimensional gel electrophoresis (2-DE) and were characterized in terms of
      their isoelectric point and molecular mass. A 2-DE database was constructed and
      is available at http://www.mpiib-berlin.mpg.de/2D-PAGE/. At present the database
      contains 67 identified protein spots. These proteins were identified after
      tryptic digestion by peptide mass fingerprinting with delayed extraction-matrix
      assisted laser desorption/ionization-mass spectrometry (DE-MALDI-MS). Proteins
      with a sequence coverage of at least 30% were introduced in the database. This
      sequence coverage could not always be obtained by using only the matrix alpha
      cyano-4-hydroxycinnamic acid (CHCA) for the mass analysis. Therefore, an
      additional mass spectrum was recorded by using 2,5-dihydroxybenzoic acid (DHB).
      Usually, additional mass peaks were detected and together with the mass spectrum
      of CHCA this resulted in the desired sequence coverage.

PMID- 10949151
TI  - Identification of proteins from human cerebrospinal fluid, separated by two
      dimensional polyacrylamide gel electrophoresis.
AB  - The aim of this work is to display the protein composition of the cerebrospinal
      fluid by two-dimensional (2-D) gel electrophoresis and identify it using
      different mass spectrometric techniques. This will enable us to present an
      overview of the proteins in human cerebrospinal fluid. The comparison of 2-D gels
      will help us to analyze the normal protein variability in healthy persons and
      specific protein variations in patients with different neurological diseases
      (e.g., morbus Alzheimer, chorea Huntington). However, it is not possible to carry
      out 2-D gel electrophoresis directly with human cerebrospinal fluid due to the
      high amount of salts, sugars and lipids present. In addition, the total amount of
      protein is only as high as 0.3-0.7 microg/microL. Therefore, concentration and
      desalting steps using precipitation and ultrafiltration are necessary. To date we
      have been able to identify more than 65 spots from 2-D gels using matrix assisted
      laser desorption/ionization-mass spectrometry and electrospray ionization-mass
      spectrometry.

PMID- 10949152
TI  - Heterogeneity of cardiac rat and human elongation factor 2.
AB  - Elongation factor 2 (EF-2) catalyses the last step of the elongation cycle,
      translocation, in the course of protein biosynthesis. A system for analyzing post
      translational modifications of EF-2, which is a single polypeptide of 857 amino
      acids, is reported and its application to cytosolic extracts of cultured neonatal
      rat heart myocytes, neonatal and adult rat cardiac tissue, and extracts of human
      left ventricular myocardium is described. Comparing different pH ranges in
      immobilized pH gradient-isoelectric focusing (IPG-IEF), a range of pH 3 - 10 and
      4 - 9 resulted in a highly defined and reproducible resolution of six different
      EF-2 variants of all extracts in the first dimension. These six variants were
      detected by the "imaging plate" (phosphor radiation image sensor) after specific
      labeling with Pseudomonas exotoxin A catalyzed [32P]ADP-ribosylation. This
      finding could be confirmed in Western blot analysis with a specific polyclonal
      rabbit antibody. Using two-dimensional polyacrylamide gel electrophoresis (2-D
      PAGE), five to six EF-2 variants could be demonstrated in all extracts. By
      application of a second IPG indicator strip to the 2-D gel, they could be aligned
      with corresponding spots in a silver-stained 2-D separation of human myocardial
      tissue, revealing that the EF-2 variants belong to the group of low-abundance
      proteins.

PMID- 10949153
TI  - Inhibition of extracellular signal-regulated kinase 1/2 activity of the breast
      cancer cell line MDA-MB-231 leads to major alterations in the pattern of protein
      expression.
AB  - Biochemical and genetic strategies have implied that aberrant signaling in the
      extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP)
      kinase pathway contributes significantly to transformed phenotypes. Using
      PD98059, an inhibitor of the ERK-kinase MEK1, we have here assessed the effects
      of ERK inhibition on the pattern of protein expression in the metastatic human
      breast cancer cell line MDA-MB-231. At a concentration of inhibitor which did not
      significantly affect cell growth, PD98059 induced large changes in the expression
      of MDA-MB-231 polypeptides. The majority of these changes were due to decreased
      expression of low-abundance proteins. Decreases of more abundant proteins such as
      glutathione-S-transferase pi, hsp80 and hsp100 were also recorded. The levels of
      a few proteins increased, among them cytokeratin 8. We conclude that PD98059
      treatment of MDA-MB-231 cells induces large changes in protein expression.

PMID- 10949154
TI  - Normative data for a new memory test: the Shum Visual Learning Test.
AB  - This study reports normative data and test-retest reliabilities for a visuo
      spatial memory test, the Shum Visual Learning Test (SVLT). Participants were 146
      Caucasians (70 males and 76 females, age range between 17-83 years). The test was
      administered to 116 participants once and 30 participants twice (1 month apart).
      Age (but not gender and education) was found to affect SVLT test performance. The
      norms, therefore, were presented according to seven age groups (viz., 17-19, 20
      29, 30-39, 40-49, 50-59, 60-69, 70+ years). Three indices (learning, retention
      after interference, and delayed retention) were derived for descriptive and
      clinical purposes. The test-retest reliabilities for all trials of the SVLT
      (except Trial 6) were found to be significant (rs ranged from .63 to .82).
      Normative data reported allow neuropsychologists to compare patient performances
      with those of appropriate controls and are important for fostering clinical
      application of this test.

PMID- 10949155
TI  - Neuropsychological characteristics of the dementia syndrome of depression: onset,
      resolution, and three-year follow-up.
AB  - In this prospective double-blind study 13 hospitalized older adults with dementia
      syndrome of depression (DSD) were compared to 14 with Alzheimer's dementia with a
      concurrent major depression on a battery of neuropsychological tests. On
      admission to hospital (onset), patients with DSD differed from those with
      Alzheimer's dementia and depression only in that the former had stronger short
      term verbal memory. Resolution of depression in patients with DSD resulted in a
      return to normal levels in most measures of verbal functioning, but nonverbal
      abilities remained impaired. Three years later those with DSD continued to
      cognitively outperform those with Alzheimer's dementia, indicating that treating
      depression in DSD appears to "buy back" up to 3 years of above-baseline cognitive
      functioning.

PMID- 10949156
TI  - Neuropsychological assesment of psychogeriatric patients with limited education.
AB  - Traditional published norms for neuropsychological tests that do not consider
      demographic effects can lead to spuriously high false positive rates among low
      educated elderly individuals. This problem may be compounded when trying to
      identify dementia in psychogeriatric patients whose cognitive functioning is also
      compromised by psychiatric illness. This study investigated the clinical utility
      of low education neuropsychological test norms to discriminate amongst demented
      and nondemented psychogeriatric inpatients and healthy community elderly with
      limited education. Results indicated that the Mattis Dementia Rating Scale
      (MDRS), the Fuld Object Memory Evaluation (FOME), the Mini-Mental State
      Examination (MMSE), and a Clock drawing task had high discriminability in
      differentiating the three groups. Application of demographically corrected norms
      has important implications for diagnosis and treatment planning, especially when
      neuropsychological status is complicated by psychiatric illness.

PMID- 10949157
TI  - Interrater reliability levels of multiple clinical examiners in the evaluation of
      a schizophrenic patient: quality of life, level of functioning, and
      neuropsychological symptomatology.
AB  - Sir Ronald Fisher used a single-subject design to derive the concepts of
      appropriate research design, randomization, sensitivity, and tests of statistical
      significance. The seminal work of Broca demonstrated that valid and generalizable
      findings can and have emerged from studies of a single patient in
      neuropsychology. In order to assess the reliability and/or validity of any
      clinical phenomena that derive from single subject research, it becomes necessary
      to apply appropriate biostatistical methodology. The authors develop just such an
      approach and apply it successfully to the evaluation of the functioning, quality
      of life, and neuropsychological symptomatology of a single schizophrenic patient.

PMID- 10949158
TI  - Use of the Halstead Category Test as a cognitive predictor of functional recovery
      in the hemiplegic upper limb: a cross-validation study.
AB  - Current motor learning theory suggests that recovery in the hemiplegic upper limb
      partially depends on the client's cognitive ability to maximize sensory feedback
      in order to activate appropriate efferent motor pathways. Study 1 investigated
      the use of the Category Test as a predictor of functional recovery. Initial
      scores on the Upper Extremity Function Test and the Category Test explained 81%
      of the variance of the discharge Upper Extremity Function score (N = 29).
      Psychological factors such as the client's attitude and motivation were less
      significant than more direct measures of the biological event. Study 2 (N = 16)
      confirmed these results and also found that stroke survivors who made fewer
      errors on the Category Test performed better on a functional disability test.
      Survivors making the fewest errors on the Category Test also showed the greatest
      amount of change in arm and hand function. The results are discussed in terms of
      the role of cognitive and biological factors that might influence recovery.

PMID- 10949159
TI  - A diagnostic test for apraxia in stroke patients: internal consistency and
      diagnostic value.
AB  - The internal consistency and the diagnostic value of a test for apraxia in
      patients having had a stroke are presented. Results indicate that the items of
      the test form a strong and consistent scale: Cronbach's alpha as well as the
      results of a Mokken scale analysis present good reliability and good scalability.
      The diagnostic value of the test was determined by comparison of test results in
      three groups of patients: 44 stroke patients with apraxia (patients), 35 stroke
      patients without apraxia (patient controls), and 50 healthy nursing home
      residents with no history of stroke (normal controls). The diagnostic value is
      expressed by means of the sensitivity and specificity and the predictive value of
      the test. In addition, Receiver Operator Characteristics (ROC) curves are
      presented. The sensitivity and specificity of the apraxia test appear to be good:
      all values are higher than 80%. The test also has high predictive value. The ROC
      curves illustrate that the test is sufficiently discriminative to allow a
      differentiation between persons with apraxia and persons without apraxia.

PMID- 10949160
TI  - Neuropsychology of sports-related head injury: Dementia Pugilistica to Post
      Concussion Syndrome.
AB  - This article reviews the existing literature in the following areas of sports
      neuropsychology: Dementia Pugilistica, concussion and Post Concussion Syndrome,
      Second Impact Syndrome, and the emerging role of the sports neuropsychologist
      regarding return to play decisions. Dementia Pugilistica is discussed as a
      condition that exists along a continuum: Although many boxers will develop mild
      neurocognitive deficits, it is not yet known what percent of these mild
      presentations will progress to diagnosable Dementia Pugilistica. Factors
      contributing to both increased and reduced risk are detailed. The role of
      neuropsychological assessment in research and clinical management is reviewed.
      Existing studies of concussion incurred during contact sports provide evidence of
      an important role for neuropsychology in assessment and management of mild head
      injuries. Issues in clinical assessment of concussion are reviewed. The
      importance of grading of concussions, monitoring of postconcussive symptom
      resolution, and the use of neuropsychological test results in return to play
      decisions is detailed. The Second Impact Syndrome is discussed with regard to
      return to play decisions. Recommendations are proposed for research and for
      clinical application of findings in sports neuropsychology.

PMID- 10949161
TI  - Structural differences of matrix metalloproteinases. Homology modeling and energy
      minimization of enzyme-substrate complexes.
AB  - Matrix metalloproteinases are extracellular enzymes taking part in the remodeling
      of extracellular matrix. The structures of the catalytic domain of MMP1, MMP3,
      MMP7 and MMP8 are known, but structures of enzymes belonging to this family still
      remain to be determined. A general approach to the homology modeling of matrix
      metalloproteinases, exemplified by the modeling of MMP2, MMP9, MMP12 and MMP14 is
      described. The models were refined using an energy minimization procedure
      developed for matrix metalloproteinases. This procedure includes incorporation of
      parameters for zinc and calcium ions in the AMBER 4.1 force field, applying a non
      bonded approach and a full ion charge representation. Energy minimization of the
      apoenzymes yielded structures with distorted active sites, while reliable three
      dimensional structures of the enzymes containing a substrate in active site were
      obtained. The structural differences between the eight enzyme-substrate complexes
      were studied with particular emphasis on the active site, and possible sites for
      obtaining selectivity among the MMP's are discussed. Differences in the P1'
      pocket are well-documented and have been extensively exploited in inhibitor
      design. The present work indicates that selectivity could be further improved by
      considering the P2 pocket as well.

PMID- 10949162
TI  - An NMR conformational analysis of cyclic bradykinin mimics. Evidence for a beta
      turn.
AB  - A detailed NMR study is carried out in acetonitrile/water solutions on three
      novel cyclic bradykinin antagonist analogues, BKM-824, BKM-870, and BKM-872, to
      examine their solution structures, and to correlate the structures with
      bradykinin antagonist and anti-cancer activities. The solution structures of the
      cyclic peptides are correlated with the structural data for known linear
      bradykinin antagonists. The sequences are: BKM-824 c[Ava-Ig1-Ser-DF5F-Oic-Arg]
      where Ava is 5-aminovaleric acid, Ig1 is alpha-(2-indanyl)glycine, F5F is
      pentafluorophenylalanine, and Oic is (2S,3aS,7aS)-octahydroindole-2-carboxylic
      acid; BKM-870; c[DArg-Arg-Add-DF5F-Oic-Arg] where Add is 12-aminododecanoic acid;
      and BKM-872; c[DArg-Arg-Eac-Ser-DF5F-Oic-Arg] where Eac is 6-aminocaproic acid.
      BKM-824 was the only peptide within this series that possessed a discernable
      solution structure. The NMR data indicate the presence of a type I beta-turn
      between residues F5F4 and Ava1, a C-terminal-like end. Molecular dynamics
      calculations show that a type I beta-turn from DF5F4 to Ava1 does exist although
      the turn was somewhat distorted. This result differs from the structures seen in
      linear bradykinin antagonists, which usually possess a type II'beta-turn at the C
      terminal end and the presence of a defined turn is correlated with bradykinin
      antagonist activity. There is no solution structure for BKM-870 and BKM-872 but a
      correlation between the primary sequence Arg(terminal)-DArg1-Arg2-long chain
      aliphatic amino acid and anti-cancer activity is evident.

PMID- 10949163
TI  - Molecular modeling of the complex of endothelin-1 (ET-1) with the endothelin type
      A (ET(A)) receptor and the rational design of a peptide antagonist.
AB  - ET-1 is the most potent vasoconstrictor known to date, causing vasoconstriction
      when bound to the ET(A) receptor. Inhibitors of the binding of ET-1 to the ET(A)
      receptor would be of immense value as potential therapeutic agents in the
      treatment of cardiovascular disorders such as angina and hypertension. We present
      here the rational design of such an inhibitor, which is arrived at on the basis
      of a model of the ET-1/ET(A) receptor complex proposed by us. The model is found
      to be consistent with binding and mutagenesis studies of ET-1 as well as of
      BQ123, a known, potent ET(A)-selective antagonist which competes with ET-1 for
      receptor binding. BQ123 is a peptidic antagonist which is constrained to adopt a
      definite conformation on account of its cyclic nature. The noncyclic peptide
      antagonist designed by us also has a unique conformation because it contains two
      dehydro-Alanine (deltaAla) residues which, on account of their planarity, cause
      the peptide backbone to bend in a specific and predictable manner. The folding
      rules for peptides containing deltaAla were derived in our earlier studies.
      Energy minimization and modelling of the complex of the designed peptide with the
      ET(A) receptor indicate that the antagonist is ET(A)-selective and the binding is
      more stable and more specific as compared to that of BQ123.

PMID- 10949164
TI  - Efficient identification and analysis of substructures in proteins using the
      kappa-tau framework: left turns and helix c-cap motifs.
AB  - We have recently (1) introduced an exact mathematical description of chain
      molecules based on discrete analogues of the curvature and torsion concepts in
      differential geometry called the kappa-tau framework, and applied it to the
      analysis of all known protein structures. We here use it to extract and analyze
      defined structural motifs from the Protein Data Bank. We find a class of left
      handed 4 residues long, open turns, tentatively called left alpha-tums, which do
      not exhibit internal backbone H-bonding and join both alpha and beta1 strands at
      the surface of many different proteins. Further, we discuss results on helix
      capping substructures such as the Schellman and alpha(L) motifs. The kappa-tau
      methodology proves to be the most efficient methodology to handle such problems
      available to date, and will greatly expand our capability to decipher the
      information hidden in the known structures and understand the fundamental
      relation between sequence and structure.

PMID- 10949165
TI  - Structure of an 11-mer DNA duplex containing the carbocyclic nucleotide analog:
      2'-deoxyaristeromycin.
AB  - 2'-deoxyaristeromycin (dAr) is a nucleoside analogue that is resistant to the
      action of DNA glycosylases. High-resolution NMR spectroscopy and molecular
      dynamics simulations were used to determine the three-dimensional structure of an
      11-mer DNA containing a single dAr.T base pair at its center. Analysis of the
      spectra revealed the existence of a right-handed duplex in solution, stabilized
      by Watson-Crick hydrogen bonding and base-stacking interactions. The carbocyclic
      sugar adopted a C1'-exo conformation and sugars of the 3'-flanking base pair had
      puckers in the O4'-endo range. The dAr.T base pair was mildly propeller twisted,
      and the dAr analogue showed a positive roll with the 3'-flanking base. Our
      findings indicate that the observed resistance of dAr-containing
      oligodeoxynucleotides to the catalytic action of DNA glycosylases relates to its
      electronic properties rather than structure, and validate the use of dAr and
      related carbocyclic nucleoside analogues for biological and structure/function
      relationship studies.

PMID- 10949166
TI  - Sequence-dependent stability of intramolecular DNA triple helices.
AB  - A set of 21 oligodeoxynucleotides were designed to fold into intramolecular
      triple helices of the pyrimidine motif under appropriate conditions. UV melting
      experiments on the triplexes which only differ in the number and distribution of
      third strand cytosines reveal the influence of sequence and pH on triplex
      stability and can be summarized as follows: (1) increasing the cytosine content
      in the third strand results in a higher thermal stability of the triplex at
      acidic pH but lowers the triplex to duplex melting temperature at neutral pH; (2)
      cytosines at terminal positions destabilize the triple helical structure as
      compared to non-terminal positions; (3) contiguous cytosines lead to a pH
      dependent destabilization of the triplex, the destabilizing effect being more
      pronounced at higher pH. Analysis of these effects in terms of the various
      interactions within a triple helical complex indicate that the sequence-dependent
      stabilities are largely determined by the extent of protonation for individual
      third strand cytosines.

PMID- 10949167
TI  - NMR evidence for base dynamics at all TpA steps in DNA.
AB  - NMR evidence is presented indicating that the exceptional conformational dynamics
      found at TpA steps in DNA is general to all immediate sequence contexts. One
      easily tractable NMR parameter that is sensitive to TpA base dynamics is the
      resonance linewidth of the TpA adenine H2 proton. This resonance experiences a
      temperature-dependent broadening due to conformational dynamics. Unusual dynamics
      at TpA steps were originally observed in the sequence context (T)pTpTpApAp(A). We
      have since shown that the evidence for TpA dynamics persists when either the
      thymine preceding the TpA step or the adenine following the TpA step is preserved
      [McAteer et al., Nucleic Acids Res. 23, 3962-3966 (1995)]. Here, in order
      establish whether or not exceptional TpA dynamics occurs in all DNA sequence
      contexts, we investigated a series of DNA sequences of the form GCNaTANbNbTANaGC,
      where N=A,T,C,G. In this family of sequences, all 16 possible immediate sequence
      context environments of the form NaTANb were examined using 10 DNA sequences. Our
      NMR results show that the TpA adenine H2 resonance contains a temperature
      dependent excess linewidth indicative of dynamics in all 16 sequence context
      environments. By studying a complete set of sequence contexts, it was possible to
      recognize trends relating resonance parameters and sequence environment. For
      example, the magnitude of the maximum linewidth is largely determined by the
      identity of the nucleotide following the TpA step and the magnitude of the
      linewidth maximum is moderately correlated (r=0.56) with the temperature of the
      linewidth maximum. The physical basis for these correlations is discussed.

PMID- 10949168
TI  - Structure of poly (dT).poly (dA).poly (dT).
AB  - The molecular structure of poly (dT).poly (dA).poly (dT) has been determined and
      refined using the continuous x-ray intensity data on layer lines in the
      diffraction pattern obtained from an oriented fiber of the DNA. The final R-value
      for the preferred structure is 0.29 significantly lower than that for plausible
      alternatives. The molecule forms a 12-fold right-handed triple-helix of pitch
      38.4 A and each base triplet is stabilized by a set of four Crick-Watson
      Hoogsteen hydrogen bonds. The deoxyribose rings in all the three strands have C2'
      endo conformations. The grooveless cylindrical shape of the triple-helix is
      consistent with the lack of lateral organization in the fiber.

PMID- 10949169
TI  - Structure of Poly (U).poly (A).poly (U).
AB  - The molecular structure of poly (U).poly (A).poly (U) has been determined and
      refined using the continuous x-ray intensity data on layer lines in the
      diffraction pattern obtained from an oriented fiber of the RNA. The final R-value
      for the preferred structure is 0.24, far lower than that for the plausible
      alternatives. The polymer forms an 11-fold right-handed triple-helix of pitch
      33.5A and each base triplet is stabilized by Crick-Watson-Hoogsteen hydrogen
      bonds. The ribose rings in the three strands have C3'-endo, C2'-endo and C2'-endo
      conformations, respectively. The helix derives additional stability through
      systematic interchain hydrogen bonds involving ribose hydroxyls and uracil bases.
      The relatively grooveless cylindrical shape of the triple-helix is consistent
      with the lack of lateral organization.

PMID- 10949170
TI  - Structure of poly (I).poly (A).poly (I).
AB  - The molecular structure of poly (I).poly (A).poly (I) has been determined and
      refined using the continuous intensity data on layer lines in the x-ray
      diffraction pattern obtained from an oriented fiber of this polymorphic RNA
      complex. The polymer forms a 12-fold right-handed triple-helix of pitch 39.7A and
      each base-triplet is stabilized by quasi Crick-Watson-Hoogsteen hydrogen bonds.
      The ribose rings in all the three strands have C3'-endo conformations. The final
      R-value for this best structure is 0.24 and the x-ray fit is significantly
      superior to all the alternative structures where the different chains might have
      different furanose conformations. This all-purine triple-helix, counter
      intuitively, has a diameter roughly 3A shorter than that of DNA and RNA triple
      helices containing a homopurine and two complementary homopyrimidine strands. Its
      compact, grooveless cylindrical shape is consistent with the lack of lateral
      organization.

PMID- 10949171
TI  - Linguistic analysis in phylogeny estimation: a case study of mtDNAs of Bovidae.
AB  - Molecular phylogenetic studies are executed by the alignment of protein or
      nucleotide sequences, followed by the construction of trees according either to
      distance, parsimony or maximum likelihood methods. Linguistic analysis was
      investigated here as an alternative method to aligning sequences. In an empirical
      study, we inferred trees for a variable number of Bovidae and sister taxa based
      on three different mitochondrial orthologous sequences. Comparison of our results
      with existing phylogenies indicated that the method, except for some still
      disputable points, was able to establish sensible systematic relationships,
      similar to patterns of radiation of the family found in recent studies.

PMID- 10949172
TI  - Theoretical analysis of DNA branch migration in the presence of a slow reversible
      initiation step.
AB  - Branched DNA structures include several DNA regions connected by three- or four
      way DNA junctions. Branched DNAs can be intermediates in DNA replication and
      recombination in living organisms and in sequence-specific DNA targeting in
      vitro. Branched DNA structures are usually metastable and irreversibly dissociate
      to non-branched products via a DNA strand exchange process commonly known as DNA
      branch migration. The key parameter in the DNA dissociation process is its
      characteristic time, which depends on the length of the dissociating DNA
      structure. Here, we predict that the presence of a slow reversible initiation
      step, which precedes DNA branch migration, can alter, to almost linear
      dependence, the "classic" quadratic dependence of the dissociation time on the
      length of the dissociating DNA structure. This prediction can be applied to
      dissociation of Y-like DNA structures and double D-loop DNA hybrids, which are
      DNA structures similar to replication bubbles. In addition, the slow initiation
      step can increase the effect of DNA sequence heterologies within the structure on
      its kinetic stability. Applications of our analysis for genetic manipulations
      with branched DNA structures are discussed.

PMID- 10949173
TI  - Structure, energetics, vibrational frequencies and charge transfer of base pairs,
      nucleoside pairs, nucleotide pairs and B-DNA pairs of trinucleotides: ab initio
      HF/MINI-1 and empirical force field study.
AB  - Geometries, interaction energies and vibrational frequencies of base pairs,
      nucleoside pairs and nucleotide pairs were studied by ab initio Hartree-Fock (HF)
      method using MINI-1 basis set and empirical Cornell et al. force field (AMBER
      4.1). A good agreement was found between HF/MINI-1 and AMBER results. In
      addition, both methods provide reasonable agreement with available high-level ab
      initio data. Finally, AMBER potential was used to determine the structure,
      energetics and vibrational frequencies of B-DNA pairs of trinucleotides.
      Stabilization energies of clusters are lowered when passing from base pairs to
      nucleoside pairs, nucleotide pairs and to pairs of trinucleotides. The lowest
      vibrations of base pairs and nucleoside pairs correspond to intermolecular
      motions of bases, specifically to buckle and propeller motions. In the case of
      pairs of larger subunits the lowest vibrations are of intramolecular nature
      (rotation around glycosidic bond, sugar and phosphate vibration). The spectra of
      these clusters became more complicated and quasi-degenerate. Intermolecular
      charge transfer between bases in H-bonded and stacked pairs is negligible, while
      a significant intramolecular charge transfer was observed.

PMID- 10949174
TI  - Cation-pi and amino-acceptor interactions between hydrated metal cations and DNA
      bases. A quantum-chemical view.
AB  - Cation-pi interactions between cytosine and hexahydrated cations have been
      characterized using ab initio method with inclusion of electron correlation
      effects, assuming idealized and crystal geometries of the interacting species.
      Hydrated metal cations can interact with nucleobases in a cation-pi manner. The
      stabilization energy of such complexes would be large and comparable to the one
      for cation-pi complex with benzene. Further, polarized water molecules belonging
      to the hydration shell of the cation are capable to form a strong hydrogen bond
      interaction with the nitrogen lone electron pair of the amino groups of bases and
      enforce a pronounced sp3 pyramidalization of the nucleobase amino groups.
      However, in contrast to the benzene-cation complexes, the cation-pi
      configurations are highly unstable for a nucleobase since the conventional in
      plane binding of hydrated cations to the acceptor sites on the nucleobase is
      strongly preferred. Thus, a cation-pi interaction with a nucleobase can occur
      only if the position of the cation is locked above the nucleobase plane by
      another strong interaction. This indeed can occur in biopolymers and may have an
      effect on the local DNA architecture. Nevertheless, nucleobases have no intrinsic
      propensity to form cation-pi interactions.

PMID- 10949175
TI  - A mezoscopic model of nucleic acids. Part 1. Lagrangian and quaternion molecular
      dynamics.
AB  - This study presents a model for mezoscopic molecular dynamics simulations with
      objects of different scale and properties e.e. atoms, pseudoatoms, rigid and
      pseudo-elastic bodies, described by the external coordinates and internal degrees
      of freedom. The Lagrangian approach is used to derive equations of motion and a
      quaternion representation is used for the description of the dynamics of rigid
      and pseudo-elastic molecular elements. Stability of the LQMD algorithm was tested
      for a 10-base pair deoxynucleotide. The total energy, momentum and angular
      momentum are conserved for time-steps up to 20 fs.

PMID- 10949176
TI  - A mezoscopic model of nucleic acids. Part 2. An effective potential energy
      function for DNA.
AB  - In this study we present an effective Potential of Mean Force (PMF) designed for
      Lagrangian and Quaternion Molecular Dynamics (LQMD) of DNA. The DNA model is
      built from pseudoatoms as well as rigid and pseudo-elastic bodies described by a
      limited number of selected Cartesian and internal degrees of freedom. Phosphate
      groups, deoxyribose rings and nucleic acid bases are represented by
      pseudoparticles, some of them with internal degrees of freedom. PMF is defined as
      the sum of effective bonded and long-range potentials. The potentials were fitted
      to numerical free energy surfaces. Over 50 free energy surfaces, each depending
      on a conformational variable (pseudobond length, angle or dihedral angle) and the
      pseudorotation phase of the nearest neighbour deoxribose ring, were computed. The
      numerical free energy surfaces were obtained from probability distributions
      derived from a 1.5 ns conventional, microscopic MD simulation of the d(GpC)9
      double helical DNA molecule. An umbrella sampling method was used to simulate
      transitions between the A and B DNA forms, and PMF reproduces these transitions.

PMID- 10949177
TI  - Steroid withdrawal in liver transplantation: benefits, risks, and unanswered
      questions.
AB  - Since the early days of clinical liver transplantation, steroid therapy has
      constituted the mainstay of maintenance immunosuppression and is still currently
      combined with cyclosporine or tacrolimus worldwide. Nevertheless, the side
      effects of long-term steroid administration, particularly diabetes,
      hypercholesterolemia, arterial hypertension, infections, and bone diseases,
      including growth retardation in children, have focused the interest on the
      feasibility of steroid-free immunosuppression. The benefits and the risks of
      steroid withdrawal (SW) after liver transplantation are overviewed. In adults,
      early (3 months after transplantation) SW has been validated by several studies,
      whereas in pediatric recipients, the timing and selection criteria to optimize
      the risk/benefit ratio of SW still constitute a matter of debate. The
      identification of the unanswered questions in this field may serve as a framework
      for future studies to better assess steroid-free immunosuppression after liver
      transplantation.

PMID- 10949178
TI  - Chronic allograft dysfunction--chronic rejection revisited.

PMID- 10949179
TI  - Renal perfusion in infant recipients of adult-sized kidneys is a critical risk
      factor.

PMID- 10949180
TI  - Do functional assays have predictive value in sibling bone marrow
      transplantation?

PMID- 10949181
TI  - Differential effects of cyclosporine A, methylprednisolone, mycophenolate, and
      rapamycin on CD154 induction and requirement for NFkappaB: implications for
      tolerance induction.
AB  - BACKGROUND: Recent experimental data indicate that the targeting of the
      costimulatory molecule CD40-ligand (CD154) may well offer an opportunity for
      tolerance induction in transplant recipients and patients with autoimmune
      diseases, although the optimal therapeutic strategy for clinical application of
      CD154 monoclonal antibody (mAb) is unclear. METHODS: We undertook vascularized
      heterotopic cardiac allograft transplantation in completely MHC-mismatched mice,
      treated recipients with CD154 mAb plus various immunosuppressive agents, and
      performed flow cytometric analysis of CD154 expression by T cells activated in
      vitro in the presence of corresponding immunosuppressive agents. We also tested
      the extent to which CD154 induction was NFkappaB-dependent by using NFkappaB/p50
      deficient mice as allograft recipients and as source of cells for in vitro
      studies of CD154 induction, and through use of proteasome inhibitors to block
      IkappaBalpha degradation and NFKB activation in wild-type mice. RESULTS:
      Concomitant use of cyclosporin A or methylprednisolone, but not rapamycin or
      mycophenolate, inhibited CD154 mAb-induced allograft survival. The differential
      effects of these agents on CD154 mAb-induced tolerance correlated with their
      capacity to inhibit activation-induced CD154 expression on CD4+ T cells. Full
      expression of CD154 expression was found to require NF-kappaB activation, and
      CD154 mAb was ineffective in NF-kappaB/p50 deficient allograft recipients or
      control mice in which NF-kappaB activation was blocked by proteasome inhibition.
      CONCLUSIONS: Strategies to use CD154 mAb clinically must take into account the
      effects of immunosuppressive agents on CD154 induction, which seems to be at
      least partially NF-kappaB dependent. Our data suggest that ligation of surface
      expressed CD154 provides an important signal that modulates T cell activation and
      thereby contributes to the effects of CD154 mAb, in addition to previously
      recognized actions involving blockade of CD40/CD154-dependent cell activation and
      activation-induced cell death.

PMID- 10949182
TI  - Multidimensional assessment of graft vascular disease (GVD) in aortic grafts by
      serial intravascular ultrasound in rhesus monkeys.
AB  - BACKGROUND: Graft vascular disease (GVD) is an incompletely understood process
      and the primary cause of late allograft failure. A nonhuman primate model was
      established to study the progression of GVD by using serial intravascular
      ultrasound (IVUS). METHODS: Aortic allografts were transplanted below the
      inferior mesenteric arteries (IMA) into 6 rhesus monkeys. Removed and re
      implanted aortic segments between renal arteries, and the inferior mesenteric
      arteries served as autografts. IVUS was performed at days 0, 24, 52, 80, and 98
      after transplantation. Vessel area (VA) and lumen area (LA) were measured from
      each cross-section at 0.5 mm intervals. Intimal index (II=100x (VA-LA/VA)) and
      corresponding vessel volumes were calculated for the whole grafts. Histologic
      features were assessed from autopsy samples using computerized morphometric
      method and a score from 0 to 3 for GVD (0=none, 3=severe). RESULTS: In
      allografts, vessel volume and luminal volume decreased significantly (P<0.05 for
      both) and the intimal index increased from 12% to 59% by day 98. These parameters
      remained unchanged in autografts. Histologic analysis of allografts showed
      concentric intimal hyperplasia and scattered mononuclear cell accumulations,
      whereas the autografts had only occasional eccentric intimal changes. The GVD
      scores were significantly higher in allografts than in autografts (median 3 vs.
      1, P=0.042). CONCLUSIONS: We introduce a nonhuman primate model of GVD that
      enables serial IVUS assessments of multiple parameters of GVD. Concentric intimal
      proliferation and decrease of vessel dimensions was observed in allografts as a
      consequence of alloimmunity. This is a potential new model for studying new
      therapies to prevent GVD or halt its progression.

PMID- 10949183
TI  - A rapid, simple, and cost-effective method for screening liver preservation
      solutions in the rat.
AB  - BACKGROUND: Rat liver transplantation models or isolated liver perfusion models
      are currently used for assessing efficacy of liver preservation methods. We
      tested the hypothesis that hepatocellular enzymes released into the washout
      solution after preservation may predict hepatic function during reperfusion and
      could thus be alternatively used for evaluating efficiency of liver preservation
      solutions. Furthermore, we applied this approach for assessing the role of
      Kupffer cells (KC) in preservation-induced liver damage. METHODS: After
      preservation in University of Wisconsin (UW) or Euro-Collins (EC) solution, rat
      livers were washed with Ringer-lactate solution. Correlations between enzymes
      released into the washout solution and hepatocyte functional parameters
      determined during reperfusion on using a blood-free perfusion model were
      investigated. RESULTS: In UW-preserved livers, acid phosphatase (ACP) activity
      correlated negatively with bile flow (R = -0.904), taurocholate intrinsic
      clearance (R = -0.841), and bromosulfophthalein excretion (R = -0.831). Both
      alanine transaminase and aspartate transaminase activities correlated with the
      functional parameters investigated. In EC-stored livers, correlation was also
      found between ACP activity and bile flow (R = -0.666). Livers stored in UW
      solution exhibited approximately 3 times lower washout activities of enzymes
      studied than livers stored in EC solution. Mitochondria isolated from UW-stored
      livers exhibited significantly better function than those isolated from EC-stored
      livers. Blockade of KC did not influence enzyme release into the washout
      solution. CONCLUSIONS: Determination of ACP, alanine transaminase, and aspartate
      transaminase activities in the washout solution can be used as a rapid, simple,
      and cost-effective way for screening liver preservation solutions. The results
      also suggest that KC were not involved in preservation-induced liver damage.

PMID- 10949184
TI  - Unique circulatory responses to exogenous catecholamines after brain death.
AB  - BACKGROUND: For better management of brain-dead donors, we developed a small
      animal model of brain death. We investigated how three catecholamines commonly
      used for the management of donors affected the cardiac function, hemodynamics,
      and tissue blood flow in the endocardium and renal cortex. METHODS: Thirty-two
      rabbits were divided into four groups. Group C served as a control. In group D,
      dopamine 10 microg/kg/min was infused from 15 to 180 min after brain death.
      Norepinephrine in group N and epinephrine in group A were infused at 0.5
      microg/kg/min. Heart rate, mean arterial pressure, left ventricular developed
      pressure, left ventricular end-diastolic pressure (LVEDP), LV dP/dt, -peak dP/dt,
      endocardial flow, renal cortical flow, and their percent changes until 180 min
      after brain death were compared. RESULTS: Acute induction of brain death caused
      sudden but transient hyperdynamic conditions, followed by profound circulatory
      collapse. Dopamine and norepinephrine increased heart rate, blood pressure, and
      endocardial flow at the expense of a reduction in renal cortical flow and had
      little effect on the other variables. Epinephrine significantly increased all
      these variables, with the exception of left ventricular end-diastolic pressure
      and -peak dP/dt, without a corresponding reduction in renal cortical flow.
      CONCLUSIONS: Dopamine and norepinephrine impaired renal perfusion and may reduce
      the viability of renal grafts before retrieval. Epinephrine improved circulatory
      collapse and pump dysfunction after brain death, while simultaneously maintaining
      renal perfusion. We conclude that epinephrine should be selected as the
      catecholamine of choice for the management of brain-dead donors.

PMID- 10949185
TI  - The role of oval cells in rat hepatocyte transplantation.
AB  - BACKGROUND: Oval cells are liver cells capable of differentiating into either
      hepatocytes or biliary epithelial cells. We compared growth of hepatocytes and
      biliary epithelial cells between spleens transplanted with oval cell-free and
      oval cell-enriched rat liver cells. METHODS: Oval cell-enriched liver cells were
      obtained from livers of adult rats that had undergone treatment with
      acetylaminofluorene and partial hepatectomy, although oval cell-free liver cells
      were obtained from livers of untreated rats. Hepatocyte and biliary epithelial
      cell growth in the spleen was evaluated by counting periodic acid-Schiff-positive
      cells and cytokeratin 19-positive cells respectively in sections from
      transplanted spleens. RESULTS: Spleens transplanted with oval cell-free liver
      cells and spleens transplanted with oval cell-enriched liver cells contained
      similar numbers of hepatocytes after 2 weeks. Numbers of hepatocytes in spleens
      transplanted with oval cell-free liver cells decreased markedly at 4 and 8 weeks,
      then increasing slightly until 32 weeks. In spleens transplanted with oval cell
      enriched liver cells, numbers of hepatocytes decreased only slightly at 4 weeks
      and then increased markedly. At 4, 8, 12, 16, 24, and 32 weeks, numbers of
      hepatocytes in spleens transplanted with oval cell-enriched liver cells
      respectively were 2.3, 3.5, 4.5, 6.7, 6.3, and 15.1 times hepatocyte numbers in
      spleens transplanted with oval cell-free liver cells. Numbers of biliary
      epithelial cells in spleens receiving oval cell-enriched liver cells showed
      changes similar to those in spleens transplanted with oval cell-free liver cells,
      increasing markedly at 4 weeks and then markedly and rapidly decreasing.
      CONCLUSIONS: Intrasplenic transplantation of oval cell-enriched liver cells
      enhanced growth of hepatocytes compared with transplantation of oval cell-free
      liver cells; this was not true for biliary epithelial cells.

PMID- 10949186
TI  - Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii.
      I. Prolongation of rat cardiac and renal allograft survival by the PG27 extract
      and immunosuppressive synergy in combination therapy with cyclosporine.
AB  - BACKGROUND: PG27 is an immunosuppressive fraction purified from an extract of a
      Chinese medicinal plant, Tripterygium wilfordii. We tested PG27 in rat cardiac
      and renal allotransplantation, and we examined the immunosuppressive interaction
      with cyclosporine (CsA). METHODS: Brown Norway (BN) rat heart or kidney
      allografts were transplanted into the abdomen of Lewis rats, which were treated
      by the intraperitoneal or oral route with PG27, CsA, or both. RESULTS: PG27
      administered intraperitoneally to Lewis recipients for 16 days at 10-30 mg/kg/day
      significantly increased the median survival time of BN heart allografts from 7 to
      18-22 days. Oral administration was effective, with cardiac allograft survival
      prolonged to > 100 days with 52 days of treatment. PG27 at 20-30 mg/kg/day
      significantly extended the median survival time of BN kidney allograft recipients
      from 9 to 36.5-77 days, and 30 mg/kg/day for 52 days extended survival beyond 200
      days. PG27 combined with CsA significantly enhanced heart and kidney allograft
      survival, even at doses of CsA ineffective when administered alone. The addition
      of 5 or 10 mg/kg/day PG27 reduced by 50-75% the CsA dose needed for 100% kidney
      allograft survival. The combination index was less than 1.0, indicating synergy
      of PG27 with CsA in prolonging cardiac and renal allograft survival. Furthermore,
      the PG27/CsA combination exerted a positive influence on renal allograft
      function. PG490 (triptolide, a constituent of PG27) and PG490-88 (a semisynthetic
      derivative of PG490) suppressed rejection of cardiac and renal allografts.
      CONCLUSIONS: The PG27 herbal extract demonstrated immunosuppressive activity by
      prolonging heart and kidney allograft survival, displaying synergy in the
      immunosuppressive interaction with CsA, and improving renal allograft function in
      combination with CsA. PG490 and PG490-88 compounds were also effective.

PMID- 10949188
TI  - Hypercholesterolemia is associated with increased kidney graft loss caused by
      chronic rejection in male patients with previous acute rejection.
AB  - BACKGROUND: Whereas acute rejection is the main risk factor for the occurrence of
      chronic rejection, mechanisms in addition to the donor-specific immune response
      probably contribute to late allograft failure. In this study, we investigated the
      possible role of hypercholesterolemia in the incidence of chronic kidney graft
      loss. METHODS: By using the actuarial method, we retrospectively analyzed the
      long-term loss of cadaveric kidney grafts in patients who had a functioning graft
      at 1 year and had received a transplant and undergone cyclosporin A therapy in
      our center between 1983 and 1997. RESULTS: As observed previously, patients with
      acute rejection during the 1st posttransplant year (n=198) had significantly
      higher actuarial graft loss at 10 years compared with those free of acute
      rejection (n=244). In patients free of acute rejection at 1 year,
      hypercholesterolemia (> or =250 mg/dl) had no impact on graft loss at 10 years.
      On the contrary, in patients with previous acute rejection, those with
      hypercholesterolemia (n=59) had a higher immunological (36.0% vs. 19.2%; P<0.01)
      and overall (50.0% vs. 25.3%; P<0.01) graft loss at 10 years compared with
      patients with serum cholesterol <250 mg/dl (n=139). Among patients with 1st year
      acute rejection, hypercholesterolemia was associated with a significant increase
      in graft loss in male but not in female recipients. Multivariate analysis
      confirmed that hypercholesterolemia was an independent risk factor for chronic
      graft loss in male patients (P<0.05). CONCLUSION: Hypercholesterolemia is an
      independent risk factor for kidney graft loss from chronic rejection in male
      patients with previous acute rejection. Correction of hypercholesterolemia could
      help to reduce kidney graft loss caused by chronic rejection in this category of
      patients.

PMID- 10949187
TI  - Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii.
      II. Prolongation of hamster-to-rat cardiac xenograft survival by combination
      therapy with the PG27 extract and cyclosporine.
AB  - BACKGROUND: PG27 is an immunosuppressive fraction purified from an extract of a
      Chinese medicinal plant Tripterygium wilfordii, which we investigated alone and
      in combination with cyclosporine (CsA) in a concordant, hamster-to-rat cardiac
      xenotransplantation model. METHODS: Golden Syrian hamster hearts were
      heterotopically transplanted into the abdomen of Lewis rat recipients, which were
      treated intraperitoneally or orally with PG27, CsA, or both. RESULTS: Combination
      therapy with 30 mg/kg(day of PG27 and CsA at 10 mg/kg/day successfully suppressed
      acute hamster-to-rat cardiac xenograft rejection. Treatment with PG27 or CsA
      alone was ineffective. Among several effective combinations, the best regimen
      involved PG27 at 30 mg/kg/day and CsA at 5 mg/ kg/day from days 8 to 35 and then
      CsA at 5 mg/kg/day from days 36 to 100, which produced 100% survival beyond 100
      days. CsA suppressed the heterospecific lymphocytotoxic antibody response and
      inhibited IgG but not IgM xenoantibody production (which led to xenograft
      rejection), whereas PG27 alone did not prevent antibody production. The PG27/CsA
      combination blocked the lymphocytotoxic antibody response and IgG and IgM
      xenoantibody production induced by cardiac xenotransplantation. CONCLUSIONS: PG27
      combined with CsA substantially prolonged hamster-to-rat cardiac xenograft
      survival, as well as completely inhibiting xenoantibody production.

PMID- 10949189
TI  - Differences in anthropometric parameters and the IFG-I-IGFBP3 axis between liver
      and renal transplant children.
AB  - BACKGROUND: Growth can be differently altered after liver and renal
      transplantation (Tx) in childhood. METHODS: We compared graft function, linear
      growth, immunosuppression and serum IGF-I (RIA) and IGFBP3 (IRMA) concentrations
      in 15 liver (5.6+/-1.1 years old) and 17 renal (7.4+/-0.1 years old) Tx patients
      who were followed for 4-6 years. RESULTS: Graft function was normal post-liver
      Tx, although in renal recipients creatinine clearance decreased significantly
      during follow-up. Liver Tx children presented an increase in mean height of
      0.92+/-0.2 SDS (P<0.01) beyond the 2nd year post-Tx, although in renal Tx
      patients height SDS did not improve. Immunosuppressive corticoid dosage could be
      decreased and discontinued in liver Tx patients, while in renal recipients it was
      maintained between 0.18+/-0.01 and 0.16+/-0.02 mg/kg/day. At 3.7+/-0.4 years post
      Tx, liver Tx patients presented higher mean serum IGF-I level, lower mean serum
      IGFBP3 value, leading to a higher mean IGF-I/IGFBP3 molar ratio, P<0.001.
      CONCLUSIONS: We found that while catch up growth coud be achieved after liver Tx,
      height SDS did not improve after renal Tx. This may be related to a reduced renal
      graft function and/or to differences in immunosuppressive corticoid dosage. In
      children with renal transplants a challenge for the future will reside in making
      it possible to substitute steroid therapy without altering graft function.

PMID- 10949190
TI  - Increased incidence of chronic rejection in adult patients transplanted for
      autoimmune hepatitis: assessment of risk factors.
AB  - BACKGROUND/AIM: It remains uncertain whether autoimmune hepatitis (AIH), as an
      original indication for orthotopic liver transplantation (OLTX), predisposes to
      the development of chronic rejection (CR) after surgery and published reports on
      heterogeneous groups of patients provided conflicting data. In this work we
      analyzed the incidence and risk factors for CR in a large cohort of adult
      patients transplanted for AIH in our unit. RESULTS: A total of 1190 adult
      patients received OLTX in our center between 1982 and 1998. A total of 77
      patients (6.5%) were transplanted for AIH and 12 (15.6%) patients from this group
      developed clinical and histological features of CR within a median time of 3.5
      months after OLTX. Patients with AIH who developed CR were younger than other AIH
      patients at OLTX (32 vs. 44.2 ys; P=0.015) and more often had histological
      features of moderate or severe acute rejection (83 vs. 34%; P=0.002) on early
      post-OLTX biopsies. The incidence of CR in AIH patients was significantly higher
      than in subjects transplanted for other indications such as primary biliary
      cirrhosis (8.2%; P<0.05), primary sclerosing cholangitis (5.2%; P<0.05) or
      alcoholic cirrhosis (2.0%; P<0.001). Also, we observed a tendency to decreased
      incidence of CR with time in all transplanted subjects. CONCLUSIONS: Apart from
      younger age at OLTX and higher incidence of severe acute rejection, patients with
      AIH who developed CR did not differ from other subjects transplanted for this
      indication. Unlike other studies, not stratified by diagnosis, recipient CMV
      negative status, young donor age, and HLA DR matching were not identified as risk
      factors for CR in AIH.

PMID- 10949191
TI  - Course of renal allograft histopathology after transplantation in early
      childhood.
AB  - BACKGROUND: We report a long-term prospective follow-up of renal allograft
      histology in children <5 years of age at transplantation (Tx). METHODS: Fifty-one
      kidney allograft recipients were prospectively followed for renal allograft
      histology and function up to 7 years after Tx. Twenty patients were recipients of
      kidneys from living related donors, and 31 were cadaveric kidney recipients. All
      patients received triple immunosuppression. Biopsies were analyzed according to
      the Banff classification and scored semiquantitatively. The "chronic allograft
      damage index" (CADI) was calculated. RESULTS: Five of seven grafts were lost
      because of nephrosis in patients with congenital nephrotic syndrome of the
      Finnish type. Most of the biopsies (52-69%) were considered normal (Banff
      classification), and the proportion with chronic allograft nephropathy did not
      increase with time. The median CADI score was 2.5 (scale: 0-36) at 1.5 years and
      3.5 at 7 years. Recipients with an acute rejection episode had higher CADI scores
      than recipients without acute rejection episode. Patients with a high CADI score
      at 3 years had inferior graft function at 5 years. Recipients <2 years of age had
      CADI scores and numbers of acute rejection episode similar to recipients between
      2 and 5 years of age. However, in contrast to the older recipients, the younger
      recipients did not improve their absolute glomerular filtration rate with time.
      CONCLUSIONS: The long-term histopathological findings were mostly mild and stable
      with time. Acute rejection episode had an impact on these changes and CADI
      predicted later graft function. Nonimmunological risk factors seem to be more
      important in the youngest recipients.

PMID- 10949192
TI  - T-cell frequency analysis does not predict the incidence of graft-versus-host
      disease in HLA-matched sibling bone marrow transplantation.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a major and sometimes fatal
      complication of allogeneic bone marrow transplantation (BMT). The prediction of
      GVHD remains an important issue in preventing morbidity and mortality after
      allogeneic BMT. In the past 10 years, there has been great interest in using the
      frequency analysis of alloreactive helper and cytotoxic T lymphocyte precursors
      (HTLp and CTLp) to detect recipient-specific alloreactivity and thus predict GVHD
      in HLA-matched related and unrelated BMT. However, the results remain
      controversial. The intention of the present study was to investigate whether
      alloreactive HTLp and CTLp frequencies measured in donor peripheral blood before
      BMT would be a useful predictor for the occurrence of acute GVHD after HLA
      matched sibling BMT. METHOD: A combined limiting dilution assay was used to
      determine alloreactive HTLp and CTLp frequencies for 42 HLA-matched sibling
      patient/donor pairs. The pretransplantation host-reactive HTLp and CTLp
      frequencies were then correlated with post-transplantation clinical outcomes of
      acute GVHD. The association between HTLp/CTLp frequencies and the incidence of
      acute GVHD was determined using the Fisher's exact test. RESULTS: The mean values
      of HTLp and CTLp frequencies for this cohort of HLA-matched sibling patient/donor
      pairs were 1:321,322 (range 1:71,000 to 1:1000,000) and 1:195,260 (range 1:3,717
      to 1:1000,000), respectively. Acute GVHD (> or =II) was observed in one of four
      patients with high (>1:100,000) HTLp frequencies and 20 of 36 patients with low
      (<1:100,000) HTLp frequencies. Similarly, 6 of 10 patients with high (>1:
      100,000) CTLp frequencies and 14 of 29 patients with low (<1:100,000) CTLp
      frequencies developed acute GVHD (> or =II). The overall correlation between
      hostreactive HTLp/CTLp frequencies and the incidence of acute GVHD in this cohort
      of patients was 42.5% and 53.9%, respectively. There was no significant
      difference in the incidence of acute GVHD between the patients with either high
      or low host-reactive HTLp/ CTLp frequencies (P=0.331 and 0.716, respectively).
      The data were also analyzed separately for the adult patient group based on GVHD
      prophylaxis with either cyclosporine alone or the combination of cyclosporine and
      methotrexate. Within these two prophylaxis groups, neither HTLp nor CTLp
      frequencies correlated with acute GVHD. CONCLUSION: Host-reactive HTLp and CTLp
      frequency analysis did not provide informative prediction for the occurrence of
      acute GVHD after HLA-matched sibling BMT.

PMID- 10949193
TI  - Hypertension after pancreas-kidney transplantation: role of bladder versus
      enteric pancreatic drainage.
AB  - BACKGROUND: Recent reports suggest that hypertension may be less common after
      simultaneous pancreas-kidney transplantation than after kidney transplantation
      alone. However, the mechanisms for this beneficial effect have not been
      delineated. We hypothesize that lower blood pressures may result from chronic
      volume depletion in patients with bladder-drained pancreatic allografts. METHODS:
      We compared the incidence and severity of hypertension 12 months after
      transplantation in 79 bladder-drained pancreas-kidney recipients and 46 diabetic
      kidney-only recipients. These two groups were compared with a smaller group of
      enterically drained pancreas-kidney recipients. Blood pressure was also compared
      before and after surgical conversion from bladder to enteric drainage in 10
      patients. RESULTS: Hypertension was significantly less common and less severe
      after pancreas-kidney transplantation than after kidney transplantation alone,
      but the benefit of the pancreas transplant was evident only in bladder-drained
      patients. Logistic regression analysis of the bladder-drained pancreas-kidney
      patients confirmed the independent impact of the pancreatic allograft on the
      presence of hypertension, indicated an independent association with serum
      creatinine concentration and donor age, but suggested no correlation with
      recipient age, race, or number of rejection episodes. A comparison of blood
      pressures before and after pancreatic conversion from bladder to enteric drainage
      indicated no significant change in the prevalence or severity of hypertension.
      CONCLUSIONS: We conclude that the beneficial effect of a pancreas transplant on
      the prevalence and severity of hypertension after simultaneous pancreas-kidney
      transplantation is limited to bladder-drained patients. Although it is possible
      that the effect is mediated by chronic volume depletion, the observation that
      blood pressure does not increase after conversion from bladder to enteric
      drainage suggests that other factors may be involved.

PMID- 10949194
TI  - Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients
      with kidney allograft rejection.
AB  - BACKGROUND: CD40 ligand (CD40L) gene expression is increased in rejecting
      allograft biopsies. We, therefore, tested the possibility that CD40L gene
      expression is heightened in peripheral CD4+ T cells during renal allograft
      rejection. METHODS: CD40L gene expression in peripheral blood CD4+ T cells from
      two renal transplant groups was measured by quantitative reverse transcription
      polymerase chain reaction (RT-PCR). Group 1: 20 patients with excellent renal
      transplant function; group 2: 25 patients with findings of acute and/or chronic
      allograft nephropathy (CAN); and group 3 of 12 normal controls. CD4+ cells were
      isolated by positive selection. The modifying effect of cyclosporine (CsA) and
      FK506 on CD40L gene expression was further tested in vitro in CD4+ T lymphocytes
      separated from pokeweed mitogen- (PWM) activated peripheral blood lymphocytes
      (PBL) preparations. RESULTS: Mean+/-SD expressions of CD40L gene, in aM, in
      groups 1-3 were as follows: 0.0052+/-0.0094; 0.022+/-0.023 (P=0.0038 vs. group
      2); and 0.014+/-0.005. Levels of CD40L gene expression correlated significantly
      with acute rejection Banff 97 score (R2=0.44, P=0.0004) and severity of
      intertubular capillary changes (ITCC) (R2=0.33, P=0.011). After in vitro
      activation, CD40L gene expression increased by approximately 4-fold and the
      addition of CsA or FK506 diminished CD40L gene expression to a base level.
      CONCLUSION: Peripheral CD4+ T cell CD40L gene expression increases significantly
      in acute rejection and CAN and may serve as a non-invasive method to monitor
      allograft function and determine the biological response to CsA and FK506.

PMID- 10949195
TI  - Quantitative assessment of cell adhesion molecule gene expression in
      endomyocardial biopsy specimens from cardiac transplant recipients using
      competitive polymerase chain reaction.
AB  - BACKGROUND: Adhesion of leukocytes to vascular endothelium is an early step in
      cardiac allograft rejection leading to migration of lymphocytes into parenchymal
      tissues. Cell adhesion molecule (CAM) protein expression appears to increase as a
      result of rejection. The relationship of CAM gene expression to rejection is less
      well defined. The goal of this study was to define cell adhesion molecule gene
      expression in relation to the presence of acute cellular rejection in
      endomyocardial biopsies from cardiac transplant recipients. METHODS: To
      quantitatively assess intercellular adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1) and E-selectin gene expression, we developed a
      competitive PCR system using nonhomologous DNA fragments (MIMICs) with
      complementary sequences to CAM gene-specific primers as internal standards. MIMIC
      fragments with known concentrations were mixed in serial dilutions with constant
      amounts of cDNA from the biopsy specimens and amplified with common primers under
      the same polymerase chain reaction conditions. The relative CAM cDNA
      concentrations were determined by comparing the density of MIMIC to target cDNA
      bands on agarose gel. ICAM-1, VCAM-1, and E-selectin mRNA concentrations were
      analyzed from 38 cardiac transplant biopsies divided into 3 groups according to
      ISHLT rejection grade: group 1-grade 0 (n=13); group 2-grade 1A or 1B (n=13);
      group 3-grade 3A (n=12). Glyceraldehyde-3-phosphate dehydrogenase (a constitutive
      gene) was quantified in the same way as CAMs to normalize the relative levels of
      CAMs. RESULTS: The results expressed as mean (1x10(-3) pM) (+/-SEM) in groups 1,
      2, and 3, respectively, were: ICAM-1; 5+/-1; 57+/-4*; 64+/-13*, VCAM-1; 0.8+/
      0.1; 6+/-1**; 9+/-1*, E-selectin; 0.4+/-0.2; 0.8+/-0.2; 0.4+/-0.1 (*P<0.001
      versus group 1; **P<0.01 versus group 1). CONCLUSIONS: ICAM-1 and VCAM-1 gene
      expression was increased during rejection in endomyocardial biopsy specimens.
      Competitive polymerase chain reaction can be used to quantitatively assess gene
      expression in biopsy specimens from patients.

PMID- 10949196
TI  - Replacement of graft-resident donor-type antigen presenting cells alters the
      tempo and pathogenesis of murine cardiac allograft rejection.
AB  - BACKGROUND: Graft-resident antigen presenting cells (APCs) are potent stimulators
      of the alloresponse. To test whether replacement of graft-resident donor-type
      APCs with those of recipient-type alters allorecognition and the pathogenesis of
      both acute and chronic rejection, we created chimeric hearts for transplantation
      into naive recipients. METHODS: To replace donor-type APCs with those of
      recipient-type, chimeric animals were created by bone marrow transplantation
      (BMT) in fully allogeneic mouse and rat strain combinations. The degree of APC
      replacement in chimeric organs was assessed phenotypically and functionally.
      Chimeric hearts were transplanted heterotopically into untreated recipients.
      RESULTS: Flow cytometric and immunohistochemical analysis did not detect residual
      bone marrow recipient-type APCs in mouse BMT chimeras. Although semi-quantitative
      reverse transcription polymerase chain reaction detected 0.001-0.01% residual
      cells, APCs isolated from chimeric organs were functionally unable to stimulate
      donor-type cells. When transplanted into naive recipients, chimeric mouse hearts
      had significantly prolonged survival but were nevertheless rejected acutely.
      Similar results were obtained in the ACI --> LEW rat strain combination. However,
      in the PVG --> DA rat model, the majority of chimeric hearts survived >100 days
      and all long-surviving hearts developed cardiac allograft vasculopathy.
      CONCLUSIONS: BMT leads to near complete replacement of organ-resident APCs. The
      virtual absence of donor-type APCs in chimeric hearts delays or prevents acute
      rejection in a strain-dependent manner. In contrast, this type of graft
      modification does not prevent cardiac allograft vasculopathy. This suggests that,
      although the CD4+ direct pathway may play a role in acute rejection, it is not
      essential for the development of chronic rejection in rodent cardiac allografts.

PMID- 10949197
TI  - Azathioprine withdrawal in stable lung and heart/lung recipients receiving
      cyclosporine-based immunosuppression.
AB  - BACKGROUND: Chronic rejection is the leading cause of graft failure after (heart
      ) lung transplantation. Therefore, many centers maintain a triple
      immunosuppressive cyclosporine-based regimen including azathioprine (AZA) during
      the long-term course after lung transplantation. However, an increased risk of
      malignancies has been attributed to prolonged immunosuppression, and there is
      evidence that less intensive immunosuppressive regimens are feasible in the long
      term course after other solid organ transplantation. Therefore, we investigated
      the effects of AZA withdrawal in stable lung transplant recipients. METHODS: A
      prospective study was performed to assess the effects of AZA withdrawal in
      patients who received a lung transplant more than 4 years ago with stable graft
      function defined by absence of rejection episodes for at least 2 years and no
      evidence of bronchiolitis obliterans. RESULTS: A total of 24 patients qualified
      for the study and 7 discontinued AZA. Despite the small number of patients,
      termination of the study became necessary after 12 months because significantly
      more grafts showed deteriorating function after withdrawing AZA (4 of 7) compared
      to recipients continuing a triple therapy (1 of 17; P<0.05). In recipients with
      deteriorating graft function conventional treatment with high-dose
      corticosteroids and reinstitution of AZA failed to stop the development of
      obliterative bronchiolitis. CONCLUSIONS: Our data reinforce the importance of a
      potent immunosuppressive regimen for the maintenance of stable graft function
      after lung transplantation.

PMID- 10949198
TI  - Ischemia reperfusion-induced dynamic changes of protein tyrosine phosphorylation
      during human lung transplantation.
AB  - BACKGROUND: We have recently demonstrated that more than 20% of lung cells
      undergo apoptosis within the first 2 hr of graft reperfusion after human lung
      transplantation. It has been found that changes of protein tyrosine
      phosphorylation are involved in the regulation of apoptosis in various cell
      types. METHODS: To determine the protein tyrosine phosphorylation status and
      related biochemistry changes, lung tissue biopsies were collected from six human
      lung transplant procedures after cold ischemic preservation (2-5 hr at 4 degrees
      C), after completing the implantation procedure (approximately 1 hr), and 1 or 2
      hr after graft reperfusion. Western blotting was performed to determine protein
      tyrosine phosphorylation and several signal transduction proteins. Protein
      tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) activities were also
      measured. RESULTS: Protein tyrosine phosphorylation was significantly increased
      after lung implantation and before reperfusion, and significantly decreased
      during the first 2 hr of graft reperfusion. The activity of Src PTKs was reduced
      by 50% during graft reperfusion, which was associated with a decrease of Src
      proteins and human actin filament associated protein, a cofactor for Src
      activation. PTP activity significantly decreased after lung implantation and
      remained at a low level 1 hr after reperfusion. After 2 hr of reperfusion,
      however, PTP activity returned to the basal level. CONCLUSION: These dynamic
      changes of PTK and PTP likely explain the observed alterations of protein
      tyrosine phosphorylation. The significant decrease in protein tyrosine
      phosphorylation may be related to the observed apoptotic cell death during human
      lung transplantation.

PMID- 10949199
TI  - Detection of HLA-specific IGG antibodies using single recombinant HLA alleles:
      the MonoLISA assay.
AB  - BACKGROUND: Because of the presence of confounding antigens, the assignment of
      HLA antibody specificity is difficult in highly sensitized patients, and the
      definition of an acceptable HLA mismatch requires a significant workload per
      patient. We describe a new ELISA method, monoLISA, for detection of
      immunoglobulin (Ig)G HLA antibody using single recombinant HLA class I monomers
      bound to microtiter plates. METHODS: HLA-A2 and -B8 monomers were synthesized and
      used as screening targets for 85 sera from renal patients. The sera contained
      various IgG and IgM HLA-specific antibodies, including anti-A2 and anti
      B8,defined in a conventional complement-dependent cytotoxicity test (CDC).
      Investigations were performed to determine possible effects on antibody binding
      of differential monomer peptide presentation as well as lack of glycosylation.
      RESULTS: A good correlation was found between CDC-defined specificities and the
      reactivity observed with HLA monomers. MonoLISA attained means of 100%
      sensitivity and 92.5% specificity compared with CDC. Neither the presence of
      different peptides, nor the absence of glycosylation of the monomer affected the
      ability of monoLISA to detect antibody. CONCLUSION: This study demonstrates that
      the mono-LISA method for HLA antibody detection is valid. Because this has the
      potential to reduce the work involved in screening sensitized patients awaiting
      transplantation for HLA antibodies, resources aimed at increasing the number of
      constructed monomers would be well targeted.

PMID- 10949200
TI  - The economic benefit of allocation of kidneys based on cross-reactive group
      matching.
AB  - BACKGROUND: Recently the United Network for Organ Sharing (UNOS) began a pilot
      study to evaluate prospectively the merits of an allocation of cadaveric kidneys
      based on broader classes of HLA antigens, called cross-reactive groups (CREG).
      The objectives of the pilot study consider patient outcomes, but not the
      potential economic impact of a CREG-based allocation. This study predicts the
      impact of a CREG-based local allocation of cadaveric kidneys on 3-year Medicare
      payments and graft survival. METHODS: The UNOS renal transplant registry was
      merged to Medicare claims data for 1991-1997 by the United States Renal Data
      System. Average accumulated Medicare payments and graft survival up to 3 years
      posttransplant for first cadaveric renal transplant recipients were stratified by
      cross-reactive group mismatch categories. The economic impact was defined as the
      difference in average 3-year costs per transplant between the current and
      proposed allocation algorithms. Average 3-year costs were computed as a weighted
      average of costs, where the weights were the actual and predicted distributions
      of transplants across cross-reactive group categories. RESULTS: Results suggest
      that an organ allocation based on cross-reactive group matching criteria would
      result in a 3-year cost savings of $1,231 (2%) per transplant, and an average 3
      year graft survival improvement of 0.6%. CONCLUSIONS: Cost savings and graft
      survival improvements can be expected if CREG criteria were to replace current
      criteria in the current allocation policy for cadaveric kidneys, although the
      savings appear to be smaller than may be achievable through expanded HLA
      matching.

PMID- 10949201
TI  - Pediatric utilization of rapamycin for severe cardiac allograft rejection.
AB  - BACKGROUND: Rapamycin is a new immunosuppressive agent that has been shown to be
      effective in the treatment of acute cardiac rejection in the adult population.
      METHODS: This case documents a pediatric patient with ongoing cardiac rejection
      that did not abate despite treatment with antithymocyte serum (RATS),
      corticosteroid pulses, and methotrexate in addition to daily prednisone,
      mycophenolate mofetil, and tacrolimus. RESULTS: Initiation of therapy with
      rapamycin resulted in a rapid resolution of cardiac rejection and reduction of
      concomitant immunosuppressive agents and few side effects. CONCLUSIONS: This case
      illustrated the utilization of rapamycin in a pediatric patient with ongoing
      acute rejection despite several modifications in treatment.

PMID- 10949202
TI  - Influenza A myocarditis developing in an adult liver transplant recipient despite
      vaccination: a case report and review of the literature.
AB  - Solid organ transplant recipients receiving chronic immunosuppressive agents are
      at increased risk to acquire influenza virus despite vaccination. Myocarditis is
      a known but rare complication of influenza infection. We present the first adult
      liver transplant recipient who received prophylactic vaccination but developed
      influenza A myocarditis. This may occur in solid organ transplant recipients,
      because they have reduced response to protein vaccines, which may leave them
      vulnerable to infections. Studies are needed to evaluate if antiviral
      chemoprophylaxis in solid organ transplant recipients during influenza season
      would be an effective preventive therapy against influenza in this high-risk
      population.

PMID- 10949203
TI  - Does glucagon stimulation predict oral glucose tolerance in patients after
      simultaneous pancreas-kidney transplantation?
AB  - BACKGROUND: Exogenous glucagon rapidly stimulates insulin secretion. This test
      has been used to estimate insulin secretory capacity, which may predict oral
      glucose tolerance in patients after pancreas transplantation. METHODS: In 32
      pancreas-kidney transplant recipients, in 10 nondiabetic kidney transplant
      recipients, and in 9 healthy control subjects, a glucagon stimulation test (1 mg
      i.v.) and a 75-g oral glucose tolerance test were performed with determination of
      glucose, insulin, and C-peptide profiles. RESULTS: Of 16 pancreas transplant
      recipients with the lowest insulin responses after glucagon, 7 had an impaired
      oral glucose tolerance, in contrast to 1 of 16 with high insulin responses
      (P=0.037). A low insulin response after glucagon was associated with
      significantly lower 120-min glucose concentrations (P=0.043) and a lower
      integrated incremental insulin response after oral glucose (P=0.006).
      CONCLUSIONS: In pancreas-kidney transplant recipients, a low insulin response
      after intravenous glucagon predicts a reduced insulin response after oral glucose
      and an impaired oral glucose tolerance. This simple test may be helpful in the
      follow-up of pancreas transplant recipients.

PMID- 10949204
TI  - Use of aerosolized inhaled epoprostenol in the treatment of portopulmonary
      hypertension.
AB  - BACKGROUND: Portopulmonary hypertension is a known complication in the liver
      transplant candidate. Intravenous epoprostenol has been demonstrated to decrease
      pulmonary artery pressures and possibly remodel right ventricle geometry.
      METHODS: In this report, we document the efficacy of inhaled aerosolized
      epoprostenol in a patient with portopulmonary hypertension. The effect was of
      rapid onset and offset. RESULTS: After 10 min of delivery, mean pulmonary artery
      pressure decreased 26%; cardiac output increased by 22%; pulmonary vascular
      resistance decreased by 42%; and the transpulmonary gradient decreased by 29%.
      There were no untoward side effects. CONCLUSION: The inhaled route of delivery of
      epoprostenol is potential alternative for the acute therapy of portpulmonary
      hypertension.

PMID- 10949205
TI  - Clopidogrel-associated thrombotic thrombocytopenic purpura/hemolytic uremic
      syndrome in a kidney/pancreas transplant recipient.
AB  - BACKGROUND: We present a case report of thrombotic thrombocytopenic
      purpura/hemolytic uremic syndrome (TTP/HUS) developing in a kidney/pancreas
      transplant recipient after the initiation of treatment with clopidogrel for
      symptomatic coronary artery disease. METHODS: A 35-year-old male kidney/pancreas
      recipient developed unstable angina 5 years after transplantation. The patient
      was treated with clopidogrel as adjunct therapy. A TTP/HUS condition developed,
      was diagnosed early, and successfully reversed with the implementation of
      plasmapheresis and cessation of clopidogrel and cyclosporine A. RESULTS: The
      patient continues taking cyclosporine A with good renal function 6 months after
      the incident, and successfully underwent coronary artery by-pass grafting 3
      months after the event. DISCUSSION: This case demonstrates that early
      identification and treatment can reverse the TTP/HUS process associated with
      thienopyridine-derived agents. We strongly recommend that drugs of the
      thienopyridine class be used cautiously in transplant recipients, especially
      those taking calcineurin-inhibitors.

PMID- 10949206
TI  - Wake-up call.

PMID- 10949207
TI  - Splenectomy for idiopathic thrombocytopenic purpura after living-related liver
      transplantation.

PMID- 10949208
TI  - Laparoscopic live donor nephrectomy: a "23-hour stay" procedure?

PMID- 10949209
TI  - Quis custodiet ipsos custodes? (Who shall keep watch over the guardians?).

PMID- 10949211
TI  - Socio-economic disparities in pregnancy outcome: why do the poor fare so poorly?
AB  - In this paper, we review the evidence bearing on socio-economic disparities in
      pregnancy outcome, focusing on aetiological factors mediating the disparities in
      intrauterine growth restriction (IUGR) and preterm birth. We first summarise what
      is known about the attributable determinants of IUGR and preterm birth,
      emphasising their quantitative contributions (aetiological fractions) from a
      public health perspective. We then review studies relating these determinants to
      socio-economic status and, combined with the evidence about their aetiological
      fractions, reach some tentative conclusions about their roles as mediators of the
      socio-economic disparities. Cigarette smoking during pregnancy appears to be the
      most important mediating factor for IUGR, with low gestational weight gain and
      short stature also playing substantial roles. For preterm birth, socio-economic
      gradients in bacterial vaginosis and cigarette smoking appear to explain some of
      the socio-economic disparities; psychosocial factors may prove even more
      important, but their aetiological links with preterm birth require further
      clarification. Research that identifies and quantifies the causal pathways and
      mechanisms whereby social disadvantage leads to higher risks of IUGR and preterm
      birth may eventually help to reduce current disparities and improve pregnancy
      outcome across the entire socio-economic spectrum.

PMID- 10949210
TI  - The fetal origin of adult disease: from sceptic to convert.

PMID- 10949212
TI  - Maternal sociodemographic characteristics as risk factors for preterm birth in
      twins versus singletons.
AB  - Many studies have examined associations between sociodemographic variables and
      preterm birth in singletons. However, almost no research has been published on
      whether variables such as maternal age, race, ethnicity, level of education and
      smoking are associated with preterm birth among twins in the same way. The
      purpose of this study was to examine such associations in twins and singletons
      comparatively. The study population consisted of all 567796 twins and 23297909
      singleton births recorded in the US birth records for 1990-95. Gestational age
      data were rigorously 'cleaned' to solve the problem of biologically implausible
      birthweight/gestation combinations in vital records. Preterm birth was defined as
      gestational age < 35 weeks. Some 25.8% of twins and 3.2% of singletons were
      preterm by this definition. Crude and adjusted relative risks (RR) were estimated
      using a modified Mantel-Haenszel procedure. We found several characteristics
      associated with preterm birth in both twins and singletons, e.g. for twins: race
      (black adjusted RR = 1.30 compared with white non-Hispanic); marital status
      (unmarried adjusted RR = 1.15 compared with married); and age (< or = 17 years
      adjusted RR = 1.39 compared with 20-29 years). A similar analysis of singletons
      revealed stronger associations between the same characteristics and preterm
      birth, e.g. the adjusted RR for black race was 2.3. These differences in RRs
      suggest that sociodemographic characteristics have weaker effects on preterm
      birth among twins than among singletons. Care must be taken in interpreting
      differences in preterm birth in twins and singletons, as their gestational age
      distributions differ so markedly.

PMID- 10949213
TI  - The importance of preterm births for peri- and neonatal mortality in rural
      Malawi.
AB  - Peri- and neonatal mortality remain high in developing countries, especially in
      sub-Saharan Africa. In the present study, we quantified and identified the most
      important predictors of early mortality in rural Malawi. Data were obtained from
      a community-based cohort of 795 pregnant women and their 813 fetuses, followed
      prospectively from mid-pregnancy. In this group, peri- and neonatal mortality
      rates were 65.3 deaths per 1000 births and 37.0 deaths per 1000 live births
      respectively. When controlled for month of birth, maternal age and selected socio
      economic variables, preterm birth was the strongest independent predictor of both
      peri- and neonatal mortality (adjusted odds ratios 9.6 for perinatal and 11.0 for
      neonatal mortality; 95% confidence intervals: [4.4, 21.0] and [3.7, 32.7]
      respectively). Weaker risk factors for mortality included a maternal history of
      stillbirth and abnormal delivery. Preterm delivery was associated with
      primiparity and peripheral malaria parasitaemia of the mother, and it accounted
      for 65% of the population-attributable risk for perinatal and 68% of the neonatal
      mortality. Successful intervention programmes to reduce peri- and neonatal
      mortality in Malawi have to include strategies to predict and prevent
      prematurity.

PMID- 10949214
TI  - Multiple malformations and maternal smoking.
AB  - The Swedish health registries were used to investigate a possible effect of
      maternal smoking on the incidence of multiple malformations. Among 1413811
      infants born in 1983-96 and with known smoking exposure in early pregnancy, 26619
      with isolated malformations and 1409 with two or more malformations were
      selected. After controlling for year of birth, maternal age, parity and
      educational level, a statistically significant association between maternal
      smoking and multiple malformations was found (OR 1.15; 95% CI 1.02, 1.29). Among
      isolated malformations, the estimated OR for maternal smoking was close to unity
      (OR 1.02; 95% CI 0.99, 1.05), but a strong heterogeneity of the magnitude of the
      association between maternal smoking and the different malformations was found.
      Among multimalformed, no such heterogeneity was indicated. The ORs for maternal
      smoking were calculated for all possible pairwise combinations of 44 selected
      malformations, but no association between maternal smoking and any specific
      combination could be detected. The ORs for maternal smoking among probable cases
      of VATER, CHARGE or OEIS non-random associations, respectively, were estimated,
      but no association was indicated between maternal smoking and any of the
      malformation complexes. The results of the present study indicate that maternal
      smoking is associated with a non-specific increased risk of multiple
      malformations, but further research is needed before such an inference can be
      made.

PMID- 10949215
TI  - Maternal height and prepregnancy body mass index as risk factors for selected
      congenital anomalies.
AB  - Previous studies have observed an increased risk of approximately twofold or more
      for neural tube defects (NTD) associated with maternal obesity before pregnancy
      based on a body mass index (BMI) of > 29 kg/m2. No additional maternal factor
      appeared substantially to influence this association. Here, we explore further
      the association between BMI and NTD risk by considering the separate
      contributions of maternal prepregnant BMI and height. We also explore whether
      selected congenital anomalies, in addition to NTDs, were associated with maternal
      height or prepregnant BMI. Data were derived from two California population-based
      case-control studies. One study comprised 538 NTD cases and 539 non-malformed
      control infants. The other study included an additional 265 NTD cases, as well as
      207 conotruncal cases, 165 limb anomaly cases, 662 orofacial cleft cases and 734
      non-malformed controls. Maternal interviews in both studies elicited information
      on maternal height and prepregnant weight. Anomaly risk was described using
      additive linear logistic regression models. Results revealed increasing NTD risk
      with increasing maternal prepregnant BMI, controlling for maternal height. These
      patterns were observed overall as well as for most race/ethnic groups. Increasing
      NTD risk for decreasing height controlling for maternal BMI was also observed in
      one NTD study, but was not as evident in the other. Elevated risks for increasing
      maternal BMI and decreasing maternal height were not observed consistently for
      the other studied anomalies. The mechanisms underlying the association between
      maternal weight, or possibly maternal height, and NTD-affected pregnancy risk are
      unknown. Exploration of other data sets will be needed to determine whether
      similar patterns of NTD risk or lack of risk for other anomalies are associated
      with the two maternal anthropometric variables, height and prepregnant weight.

PMID- 10949216
TI  - Incidence of childhood cancer in Ho Chi Minh City, Vietnam, 1995-97.
AB  - Incidence rates of childhood cancer for the city of Ho Chi Minh are presented for
      the first time. For the 3-year period 1995-97, a total of 302 cancer cases were
      registered in children under 15 years of age, with a male to female ratio of 1.1.
      The overall crude rate was 78.8 and the age-standardised incidence rate was 88.4
      per million person-years, which was low in comparison with other countries in
      eastern Asia and with the predominantly white population of Australia. Leukaemia
      (principally acute lymphocytic), brain tumours and lymphomas were the most common
      childhood neoplasms, which is consistent with the pattern observed in other
      registries of the region. The rate of retinoblastoma was higher than in the other
      regional registries. On the other hand, no cases of hepatocellular carcinoma were
      registered.

PMID- 10949217
TI  - Childhood brain tumours and exposure to animals and farm life: a review.
AB  - Brain tumours are the most common solid tumour in children. However, little is
      known about their aetiology, and only a small percentage of cases can be
      attributed to established risk factors. Exposure to farm animals and pets have
      been considered as possible risk factors for childhood brain tumour (CBT)
      development for several reasons. Numerous factors associated with farm life,
      including bacteria, pesticides, solvents and some animal oncogenic viruses, have
      been found to induce brain tumour formation in animals. Some studies have found
      viral gene sequences in human brain tumours. Epidemiological studies of brain
      tumours in adults have reported an increased risk among veterinarians and
      farmers. In this review, data are examined from seven case-control studies
      published between 1979 and 1998 that considered a possible relationship between
      fetal or childhood exposure to farm animals or pets and CBT. Five of the seven
      studies examined childhood farm residence or exposure of mother or child to farm
      animals and, of these five, four reported elevated risk for CBT with odds ratios
      (OR) ranging from 0.9 to 2.5 for maternal exposures and from 0.6 to 6.7 for
      children's exposures. Later studies that were larger subsequently examined
      histological type and reported excess risk for primitive neuroectodermal tumours
      (PNETs) with farm residence prenatally (OR = 3.7, CI = 0.8, 24) or in childhood
      (OR = 5.0, CI = 1.1, 4.7). Increased risk of PNET was also associated with
      maternal exposure to pigs (OR = 12, CI = .1, 47) or poultry (OR = 4.0, CI = 1.2,
      13). The results of these studies showed few other consistent relationships
      between farm life or farm animals and CBT.

PMID- 10949218
TI  - Reliability of demographic, smoking and occupational data provided by mothers vs.
      fathers in a childhood cancer study.
AB  - A large case-control study of children was used to test mothers' reporting of
      information on fathers' background, lifestyle and occupational factors. For a
      subset (104) of 1341 enrolled families, both parents were interviewed about
      fathers' characteristics. Reliability of reporting was determined for fathers'
      race, education, smoking status, non-recent job history and use of occupational
      agents. The ability of mothers to report fathers' race, education and smoking
      status was high (kappa > 0.70). Mothers were generally able to report jobs held
      by the fathers in the 5 years preceding the birth of the child, but reliability
      was higher for jobs held for longer (kappa typically above 0.70), rather than
      shorter periods (kappa above 0.40). The finding that mothers' reporting on
      fathers' background, lifestyle and non-recent job history was reliable is
      encouraging, because many studies on childhood health rely exclusively on
      information from interviews with mothers. However, mothers were not reliably able
      to describe exposure to specific occupational agents.

PMID- 10949219
TI  - Assessing number-specific error in the recall of onset of last menstrual period.
AB  - The goal of this investigation was to determine whether women who did not report
      preferred numbers for their last menstrual period (LMP) may be a group of women
      who are particularly careful in keeping track of their menstrual cycles and
      therefore have more accurate LMP dating--based on a comparison with ultrasound
      examinations. We also sought to estimate the frequency with which preferred
      numbers are reported in different sources of data and for different subgroups of
      women. First, we examined the 1987 California birth certificates in which LMP was
      collected at the time of birth (n = 504853). We also examined the records of
      43880 women participating in the California Alpha-fetoprotein (AFP) Screening
      Program between 1986 and 1987, for whom gestational ages based on both early
      ultrasound examination and LMP were collected before 20 weeks of gestation. In
      the 1987 California birth certificates, seven numbers--1, 5, 10, 15, 20, 25 and
      28--were recorded more frequently than expected. An estimated 12.9% of these
      records had preferred numbers. The most frequently recorded number was 15,
      occurring 2.5 times more often than expected (P < 0.01). In the data of the AFP
      Screening Program, the same seven numbers were preferred, and approximately 7.9%
      of records were affected by number preference. Comparisons with measurements of
      gestational age based on ultrasound demonstrated that LMP-based gestational ages
      in which non-preferred numbers are reported for the LMP are slightly more
      accurate than those in which preferred numbers are reported (P < 0.01). In most
      cases, number preference appears to introduce small errors into measurements of
      gestational age, probably as a result of rounding. Thus, the effect of number
      preference may be primarily of interest to research studies in which small errors
      in the measurement of gestational age will have a significant impact on findings.

PMID- 10949220
TI  - Seasonal variation in the prevalence of persistent otitis media with effusion in
      one-year-old infants.
AB  - The objective of this population-based cohort study was to evaluate the
      prevalence of persistent otitis media with effusion (OME) and its seasonal
      variation in 12-month-old infants. All 30099 infants born in the eastern part of
      The Netherlands between 1 January 1996 and 1 April 1997 were invited for hearing
      screening, comprising a protocol of three possible tests. Those who failed all
      three screening tests were referred to an ENT clinic for examination. Prevalences
      (i.e. the probability that a child would fail all the screening tests) were
      calculated by searching for the best logistic model for the first, second and
      third screening test as well as for the visit to an ENT department. By
      multiplying the prevalences found by the different models with each other, a
      prevalence was calculated that accounted for increasing age and the timing of the
      successive hearing tests. Furthermore, 95% confidence intervals were calculated
      for this age-season-corrected prevalence. When all the children attended the
      hearing tests at 9, 10, 11 and 12 months of age and when the number of births was
      the same in all months, the overall prevalence was 4.8% [95% CI 4.3, 5.2]. The
      highest prevalence (8.0%) was found in April, and the lowest (1.5%) in October.
      Rates of bilateral OME during the late winter months were twice as high as those
      during the late summer.

PMID- 10949221
TI  - The relationship between inside and outside ambient temperatures in Christchurch,
      New Zealand.
AB  - The objective of this study was to examine and identify relationships between
      hourly recorded meteorological temperature and ambient temperature, measured from
      within the home-sleeping environment of young infants' homes in Christchurch, New
      Zealand. From 1991 to 1994, home polysomnography recordings were conducted for up
      to 6 weeks on 32 infants aged between 2 and 24 weeks. One of the recorded signals
      was ambient room temperature. In total, 15735 hourly recordings of this
      temperature were available for analysis. The New Zealand Meteorological Service
      supplied hourly recordings of climatic temperature, collected over this time,
      from an exposed site that was considered to be representative of weather
      conditions for Christchurch. Temperature seasonality, hourly climatic temperature
      recordings and the interaction of these variables were found to be significantly
      related to the indoor ambient temperature recordings (all had P < 0.001).
      Fluctuations in hourly recorded indoor temperature appeared to lag outdoor
      temperature fluctuations by approximately 2 h; hence, a strong autocorrelation
      was identified in the regression residuals. The most parsimonious autoregression
      model accounted for 97% of the variability in the hourly indoor temperature
      measurements (r2 = 0.97). In Christchurch houses, which typically have poor
      thermal insulation properties, yet have no central heating capabilities, a very
      strong association between indoor and outdoor temperatures was clearly
      demonstrated.

PMID- 10949222
TI  - The influence of parental age on the risk of Wilms' tumour.

PMID- 10949223
TI  - Domestic violence--a women's health issue of great consequence.

PMID- 10949224
TI  - Domestic violence during pregnancy. The prevalence of physical injuries,
      substance use, abortions and miscarriages.
AB  - BACKGROUND: The aim of this study was to estimate the prevalence of physical
      injuries, alcohol and tobacco use, abortions and miscarriages due to domestic
      violence during pregnancy and to compare socio-economic background factors
      between abused and non abused women. METHOD: Personal interview combined with a
      standardized questionnaire involving 207 pregnant Swedish born women married to
      or cohabiting with Swedish born men. The women were consecutively chosen from
      three different antenatal clinics in Goteborg, Sweden. RESULTS: Overall 30 women
      were abused during the current pregnancy as defined from the category 'symbolic
      violence' in the Severity of Violence Against Women Scale (SVAW). The most
      frequent targets for physical abuse were: the upper arm, the forearm, and the
      face and neck region. Ninety-five percent of women abused during pregnancy had
      been abused prior to the pregnancy. Notable was the finding that 4.3% of the
      pregnant women had been exposed to serious violence. Abused women were
      significantly younger and single, had lower income and education compared to the
      non abused women. In the group of abused women a higher proportion of women had
      undergone one or more abortions than in the non-abused group. Smoking and alcohol
      use among partners were strongly correlated with physical and sexual abuse.
      CONCLUSIONS: The results suggest that in antenatal and obstetric clinics,
      emphasis should be focused on previous history of abuse and a complete physical
      examination of the women. Since bruises often were located at hidden areas of the
      body, it is of importance to scrutinize those sites as part of a routine
      examination. It is also important to look for common defensive marks on the
      forearms. The partner's cigarette and alcohol use is also an important piece of
      information regarding risk factors connected to domestic violence.

PMID- 10949225
TI  - Doppler ultrasound of the maternal uterine arteries: disappearance of abnormal
      waveforms and relation to birthweight and pregnancy outcome.
AB  - BACKGROUND: To assess whether the gestation at which abnormal uterine artery
      waveforms disappear is related to birthweight and complications of pregnancy.
      METHODS: A prospective study of outcome of pregnancy after a uterine artery
      Doppler screening program set in an inner city teaching hospital. One thousand
      five hundred and twenty-four consecutive women attending the Obstetric Department
      for a routine anomaly scan at between 19 and 21 weeks gestation had maternal
      uterine arteries assessed using color wave Doppler. Those women in whom the flow
      was deemed abnormal were recalled for a further scan at 24-26 weeks gestation.
      The main outcome measures were birthweight, gestation at delivery and incidence
      of pre eclampsia. RESULTS: The women in whom the uterine artery blood flow was
      normal at 20 weeks had babies with significantly higher mean birthweight than
      those who normalized between 20 and 24-26 weeks gestation ('late normalizers')
      after adjustment for confounding factors; gestational age, maternal height,
      parity, ethnic group and smoking (mean difference=173 g, 95% confidence intervals
      42 to 303 g). CONCLUSIONS: The timing of trophoblast invasion, as reflected by
      abnormal uterine artery waveforms, may have an effect on birthweight.

PMID- 10949226
TI  - Three-dimensional sonographic features of fetal central nervous system anomaly.
AB  - OBJECTIVE: To visualize an intracranial structure of the fetal central nervous
      system (CNS) anomaly using transabdominal three-dimensional (3D) sonography.
      METHODS: A total of 12 cases with fetal CNS anomalies (one unilateral
      ventriculomegaly; three hydrocephalus; three anencephaly; three
      holoprosencephaly; one Dandy-Walker cyst; and one enlarged cisterna magna) from
      17 to 37 weeks of gestation were studied with transabdominal 3D sonography (3.5
      MHz). RESULTS: In unilateral ventriculomegaly, insight view of dilated lateral
      ventricle, especially dilated atrium was depicted. In hydrocephalus, severely
      dilated bilateral ventricles and thin brain mantle were very clearly shown. In
      anencephalus, an absence of the brain and defect of the vault of the skull was
      clearly noted. In holoprosencephaly, absent interhemispheric fissure, common
      ventricle, and the extent of thalamic fusion were evident. In Dandy-Walker cyst,
      cerebellar hemisphere was clearly depicted due to the agenesis of cerebellar
      vermis. In enlarged cisterna magna, posterior intracranial view of the fetus
      showed a large space of cisterna magna. Although the diagnosis of each CNS
      anomaly was made using conventional two-dimensional sonography, 3D sonography
      proved most helpful delineating the exact nature and anatomic level of the
      anomaly. CONCLUSIONS: These results suggest that 3D sonography provides a novel
      means of visualizing fetal CNS anomalies in utero. However, it should be noted
      that our 3D sonography cannot depict intracranial brain structures in normal
      fetuses or some CNS anomaly such as intracranial tumor.

PMID- 10949227
TI  - Hyperemesis gravidarum in a contemporary population in Oslo.
AB  - BACKGROUND: Sociodemographic studies of hyperemesis gravidarum are conflicting.
      During the last few years, there has been a clinical impression in Norway that
      immigrants are more afflicted than ethnic Norwegians. METHODS: Of 175 patients
      hospitalized with the diagnosis hyperemesis gravidarum 1993-1997, 120 had
      complete records and were compared to a control group of 115 patients without
      hyperemesis gravidarum, drawn at random from the labor ward protocol. VARIABLES:
      Ethnicity, age, height, weight at the beginning and at the end of pregnancy, body
      mass index, gravidity, parity, smoking, gestational age at labor, birth weight,
      placental weight. The patient's first name was used as an indication of
      ethnicity. Having a non-Norwegian name means, in the majority of cases, being a
      first generation immigrant from a developing country. STATISTICS: SPSS
      statistical package for regression analyses, the chi-square test with Yates
      correction and the Mann-Whitney U-test. RESULTS: Risk factors for hyperemesis:
      non-Norwegian name (OR 3.4, 95% CI 1.5-7.6), female sex of the infant (OR 2.6,
      95% CI 1.3-5.3), gravidity number (OR 1.4, 95% CI 1.1-1.9). These two last
      variables were of significance only in patients with a Norwegian name. The
      hyperemesis group had a lower weight gain and birth weight. In a stepwise
      multiple regression birth weight (g) was dependent on weight increase (kg)
      (B=19.0, p=0.001), weight in early pregnancy (kg) (B=8.0, p =0.02) and parity (B=
      107.1, p=0.02). Hyperemesis, when corrected for weight increase, did not
      influence birth weight. CONCLUSIONS: Risk factors vary between different
      populations. Hyperemesis patients are at risk of having infants with reduced
      growth.

PMID- 10949228
TI  - Smoking during pregnancy increases the risk of preterm births among parous women.
AB  - BACKGROUND: We wanted to study a possible association between smoking during
      pregnancy and preterm birth. METHODS: A population based prospective study was
      performed among 7,236 consecutive pregnancies over seven years delivered at one
      birth clinic. Smoking habits were obtained at a routine ultrasound examination
      around 18 gestational weeks, and preterm birth was defined as delivery of a child
      between 24 and 37 gestational weeks. We estimated relative risk (odds ratio)
      between smoking, possible confounding variables and preterm birth using multiple
      logistic regression analysis. RESULTS: Overall, 1,769 (25%) women said that they
      smoked every day during their pregnancy. The smoking women had an increased risk
      of preterm delivery compared with non-smokers (odds ratio 1.53, 95% confidence
      interval 1.24, 1.89). However, this association was only demonstrated among the
      multiparous women (odds ratio 1.88, 95% confidence interval 1.39, 2.54). The
      association was statistically significant after adjusting for maternal age,
      diabetes, cervical conization, preeclampsia, placental abruption and placenta
      previa in a multivariate analysis, and we observed a dose-response effect of
      maternal smoking on preterm birth among multiparous women. CONCLUSION: For
      multiparous women smoking during pregnancy increases the risk of preterm
      delivery, and there seems to be a dose-response effect of smoking.

PMID- 10949229
TI  - Adequate timing of fetal ultrasound to guide metabolic therapy in mild
      gestational diabetes mellitus. Results from a randomized study.
AB  - BACKGROUND: Ultrasound assessment of abdominal circumference early in the third
      trimester had been proposed to introduce insulin therapy in order to prevent
      fetal overgrowth in women with mild gestational diabetes mellitus. The purpose of
      this study was to investigate adequate weeks gestation timing for testing this
      parameter. METHODS: One hundred and forty-one women were included in a randomized
      trial. Seventy-three women were evaluated at both 28 and 32 weeks gestation
      whereas 68 women were investigated only at 32 weeks gestation. In both groups,
      insulin therapy was promptly started when abdominal circumference exceeded the
      75th percentile. Macrosomic rates were compared using the Fisher's exact test.
      RESULTS: Twenty-nine women whose fetal abdominal circumference exceeded the 75th
      percentile were considered eligible for insulin therapy. In this group, we
      observed a statistically significant increase in the percentage of macrosomic
      infants born from women whose ultrasound abdominal circumference assessment was
      performed only at 32 weeks gestation when compared to women evaluated at both 28
      and 32 weeks gestation (71.43% vs 33.33%, p<0.05). CONCLUSIONS: Our results
      support the need for fetal ultrasound at 28 weeks gestation to direct metabolic
      therapy since insulin administration introduced after 32 weeks gestation has a
      poor effect on fetal growth.

PMID- 10949230
TI  - Birth outcomes in pregnant women treated with low-molecular-weight heparin.
AB  - BACKGROUND: Pregnancy and puerperium are associated with an increased risk of
      venous thromboembolism. Low-molecular-weight heparin is the anticoagulant of
      choice in pregnant women because, unlike warfarin, it does not cross the
      placenta. However, there are limited data on the risk of adverse birth outcomes
      following use of low-molecular-weight heparin in pregnancy. PATIENTS AND METHODS:
      We performed a population-based cohort study to examine the safety of low
      molecular-weight heparin use in pregnancy using data from the
      Pharmacoepidemiological Prescription Database, The Danish Medical Birth Registry
      and the Regional Hospital Discharge Registry in North Jutland County, Denmark.
      The birth outcomes in a cohort of 66 pregnant women treated with low-molecular
      weight heparin between 1991-98 were compared with the birth outcomes of 17,259
      pregnant women who did not receive any prescriptive drugs during pregnancy.
      RESULTS: No increased risk of malformations, low birth weight or stillbirth was
      found. However, an increased risk of pre-term delivery was found (odds ratio:
      2.11, 95%, confidence interval: 0.96-4.65), which could reflect inherited
      thrombophilia as an indication of low-molecular-weight heparin. CONCLUSION: We
      have provided additional evidence of the safety of low-molecular-weight heparin
      use in pregnancy.

PMID- 10949231
TI  - Erythrocyte zinc protoporphyrin testing in pregnancy.
AB  - BACKGROUND: To compare the usefulness of serum ferritin, hemoglobin and
      erythrocyte zinc protoporphyrin estimations as indicators of the need of iron
      supplementation in pregnancy. METHODS: In 97 healthy pregnant women serum
      ferritin, hemoglobin and erythrocyte zinc protoporphyrin concentrations were
      measured at each trimester period. Iron supplementation was prescribed at
      hemoglobin values below 113 g/L. RESULTS: Neither in the first nor in the second
      trimester differences in serum ferritin and erythrocyte zinc protoporphyrin
      values have been found between women who got iron therapy prescribed and women
      who did not get iron therapy, whereas already in the first trimester hemoglobin
      values were lower in the group that got iron therapy. These results indicate that
      hemodilution rather than iron deficiency determined which women got iron therapy.
      In the third trimester 14 out of 80 women without iron supplementation had
      depleted iron stores and a significant erythrocyte zinc protoporphyrin increase,
      indicating evolving iron deficiency anemia. However, only five of them showed
      hemoglobin levels below 113 g/L and got iron therapy. Low serum ferritin levels
      were found in 23% of the women at booking and in 92% in the third trimester.
      Serum ferritin levels neither predicted the development of iron deficient
      erythropoiesis nor of anemia. CONCLUSIONS: Iron deficiency can neither be
      diagnosed nor predicted by serum ferritin or hemoglobin measurements at booking
      or later on in pregnancy. Erythrocyte zinc protoporphyrin measurements can be of
      help in determining which women have iron deficient erythropoiesis and may
      benefit by iron therapy.

PMID- 10949232
TI  - Predictive value of serum interleukin-6 and -8 levels in preterm labor or rupture
      of the membranes.
AB  - BACKGROUND: The aim of this prospective study was to examine if serum
      concentrations of cytokines are of value in the identification of patients at
      risk for preterm delivery. METHODS: Interleukin- 1beta,2,4,6,8 and tumor necrosis
      factor alpha were determined between 25 and 37 weeks of gestation in the serum of
      72 consecutive patients with preterm labor, 38 patients with preterm rupture of
      the membranes, and 24 healthy pregnant women as a control group. Material was
      collected within 18 hours after hospitalization and was immediately centrifuged
      and shock frozen. RESULTS: Significantly increased serum levels were found for
      interleukin-6 and -8 in patients with preterm labor or preterm rupture of the
      membranes when compared to the control group (p<0.001 and p<0.005, respectively).
      In patients with preterm rupture of the membranes and interleukin-6 levels above
      the median of 4.0 pg/ml the delivery occurred significantly earlier than in
      patients with lower levels (1 versus 5.5 days; p=0.005). Patients of both
      pathology groups with detectable (>18 pg/ml). Interleukin-8 levels had a shorter
      pregnancy duration when compared to other patients (p=0.05 for preterm labor and
      p=0.04 for preterm rupture of the membranes). Interleukin-1beta,2,4, and tumor
      necrosis factor alpha were not correlated with clinical outcome. CONCLUSIONS:
      Increased serum interleukin-6 and -8 levels are associated with a shorter
      interval between onset of preterm rupture of the membranes and delivery and
      should therefore be further evaluated for their use in clinical practice.

PMID- 10949233
TI  - Association between external pelvimetry and vertex delivery complications in
      African women.
AB  - OBJECTIVE: To assess association between external pelvimetry and delivery
      complications in vertex presentation. METHODS: Prospective cohort study of 2,413
      pregnant women antenatally measured for height and external pelvimetry in four
      hospitals of the former Republic of Zaire. OUTCOME MEASURES: Complications during
      delivery of single fetus weighing 2,000 g or more in vertex presentation. Cut-off
      values at risk for delivery complications were height and pelvic distances
      closest to the study population 10th percentile. RESULTS: In univariate analysis,
      maternal height showed significant relative risk for predicting primary cesarean
      section for failure to progress: 2.0 (95% CI=1.0-4.1; p=0.050) and vacuum or
      forceps delivery: 15.7 (95%, CI=6.6-37.5; p<0.001). Selected external pelvic
      distances showed significant relative risks for predicting the following
      complications: primary cesarean section for failure to progress, elective repeat
      cesarean section, vacuum or forceps delivery and spontaneous intrapartum
      stillbirth. Among pelvic predictors, transverse diagonal (TD) of Michaelis sacral
      rhomboid area was associated with all of these complications. Intertrochanteric
      (IT) diameter was associated with three of them. The relative risks ranged from
      2.3 (95% CI=1.1-6.3; p=0.030) to 9.6 (95% CI=4.1-22.5; p<0.001) for these
      strongest predictors. CONCLUSIONS: External pelvic distances help to predict
      vertex delivery complications in African women. The predicted complications are
      compatible with the cephalopelvic disproportion concept (CPD). After validation
      of current results in a separate cohort, measurements of IT and/or TD are
      recommended to improve antenatal screening of women at risk for CPD in limited
      resources settings.

PMID- 10949234
TI  - Swedish maternal mortality in the 19th century by different definitions: previous
      stillbirths but not multiparity risk factor for maternal death.
AB  - BACKGROUND: The high maternal mortality levels in today's developing countries
      were also found throughout the history of currently affluent countries. The
      parish information system in Sweden offers unique possibilities for research in
      historical cohorts. Furthermore, vital events surveillance systems are scarce in
      today's developing countries. METHODS: This cohort study covers 42,387 mothers
      who gave birth to 150,932 infants during the 19th century in the Skelleftea and
      Sundsvall areas. Among these women, 1,237 were dead within one year after
      delivery. The analysis of the cause of these deaths was done according to the
      various ICD definitions. Parity five and above was defined as grand multiparity.
      RESULTS: Maternal mortality ratios, deaths per 100,000 live births were as
      follows: 256.4 (direct obstetric deaths), 320.7 (direct and indirect obstetric
      deaths), 489.2 (pregnancy-related deaths), 347.8 (late maternal deaths) and 837.0
      (maternal deaths and late maternal deaths). In this study, 59% of all maternal
      deaths occur within the first 42 days of delivery, two thirds of them having
      direct and indirect obstetric causes. Of the late maternal deaths, the bulk were
      infectious or other indirect deaths, mirroring more general female mortality and
      the pre-existent endemic situation of tuberculosis and other infectious diseases.
      The combination of previous stillbirth and infant death represented the highest
      risk ratios, RR 2.77-3.62, while grand multiparity was not associated with
      increased risk. Urbanized and industrialized areas tended to have higher maternal
      mortality. CONCLUSIONS: In conclusion, this study shows that the mother's
      reproductive history was the most important risk factor measured for all
      definitions of maternal death. Grand multiparity did not increase the risk of
      maternal death. Maternal mortality ratio varied threefold in the study
      population, depending on the definition used. The high mortality ratios found in
      this study, only declining by the end of the century, should be interpreted as a
      general condition of the society since no significant differences could be
      perceived regarding social class, while unmarried women were more at risk.

PMID- 10949235
TI  - Child rate, pregnancy outcome and ovarian function in females with classical 21
      hydroxylase deficiency.
AB  - BACKGROUND: Ovulatory disorders and decreased fertility rates have been found in
      females with classical 21-hydroxylase deficiency (21-OHD). We analyzed the
      pregnancies of 29 females with classical 21-hydroxylase deficiency and examined
      16 of these women in a cross-sectional study. METHODS: The child rate of the 29
      patients was compared with that in the general Finnish female population with
      equal age distribution.The cross-sectional study of the 16 patients included a
      standardized questionnaire, clinical examination, ultrasonography of the internal
      genitalia, basal measurements of serum steroids, sex hormone binding globulin,
      PRL, gonadotropins and plasma ACTH. RESULTS: The child rate was significantly
      lower than that in the general population (0.34 vs 0.91; p<0.001). A total of 13
      pregnancies could be registered. From these pregnancies, ten healthy children
      were born, all for females with a simple virilizing disease. None of the nine
      females with salt wasting 21-OHD had any children or had sought treatment for
      infertility. In the cross-sectional study, females with regular menses (5/16;
      31%) had well controlled adrenal androgen secretion and they had normal serum
      progesterone concentrations whereas the females with irregular menses (11/16;
      69%) were often undersubstituted and presented with high serum progesterone
      concentration in the follicular phase. Polycystic ovaries could not be detected
      in any of these patients. CONCLUSIONS: Females with simple virilizing 21-OHD
      often have irregular menses but their final prognosis for fertility seems to be
      better than previously reported. On the contrary, our study confirms the
      extremely low child rate in the salt wasting group.

PMID- 10949236
TI  - Changing trends in genital herpes simplex virus infection in Bergen, Norway.
AB  - AIM OF STUDY: To document the proportion of each herpes simplex virus (HSV) type
      in genital HSV infection and changes over time during a 10 year period. DESIGN:
      Retrospective comparative study in sexually transmitted disease (STD) patients
      with genital HSV infection at the outpatient clinic for STD, Haukeland Hospital,
      Bergen, Norway. RESULTS: HSV-2 was the major cause during the 80's, whereas HSV-1
      constitutes a greater part of the cases during the 90's, especially in female
      patients and in the younger age groups with primary or initial disease, where HSV
      1 is the causative viral type in up to 70-90% of the cases. CONCLUSION: The
      documented change from HSV-2 towards HSV-1 in cases of genital HSV infection may
      have implications as to prognosis, future usefulness of vaccines, present and
      future usefulness of new type-specific serological tests.

PMID- 10949237
TI  - Significance of endovaginal ultrasonography in assessing tamoxifen-associated
      changes of the endometrium. A prospective study.
AB  - BACKGROUND: A prospective study was conducted investigating the value of
      endovaginal ultrasound in the assessment of tamoxifen-associated changes of the
      endometrium in patients with breast cancer. METHODS: Seventy postmenopausal
      patients with breast cancer treated with anti-estrogens for at least 6 months
      were entered. Those with bleeding disorders and/or an endometrial thickness of >
      or =10 mm found on ultrasonography underwent hysteroscopy and dilatation and
      curettage (D&C) for further histological evaluation. In 22 patients, positive
      ultrasound findings could be compared with histopathology. RESULTS: 82% of the 22
      patients with positive sonographic findings had a glandular-cystic hyperplasia or
      a glandular-cystic polyp. No adenomatous hyperplasia or endometrial cancer was
      observed in our series. CONCLUSION: Vaginal ultrasound represents a useful
      diagnostic tool to detect tamoxifen-associated changes of the endometrium. A
      threshold of 10 mm endometrial thickness appears suitable to identify endometrial
      abnormalities while reducing the rate of false-positive findings to an acceptable
      level. However, the role of vaginal ultrasound in screening for endometrial
      cancer or premalignant lesions remains uncertain.

PMID- 10949238
TI  - Termination of second trimester pregnancy with mifepristone and gemeprost. The
      clinical experience of 197 consecutive cases.
AB  - BACKGROUND: Earlier controlled clinical trials have demonstrated that combined
      treatment with the antiprogestagen, mifepristone and a suitable prostaglandin
      reduce the induction to abortion time in second trimester abortion. The aim of
      this study was to describe the results of the 197 consecutive second trimester
      terminations performed in routine clinical practice at our Department from 1996
      to 1998. METHODS: The report is based on 197 consecutive second trimester
      abortions including live pregnancies and missed abortions, carried out in 192
      women. The women were treated with 600 mg mifepristone followed 24 to 48 hours
      later by 1 mg gemeprost administered every 6 hours four times. If abortion had
      not occurred, 1 mg gemeprost was administered every 3 hours for the next 12
      hours. After expulsion of the fetus a surgical evacuation of the uterus was
      routinely performed up to 18 weeks gestation and thereafter when needed. The
      induction to abortion time was defined as the interval between the insertion of
      the first gemeprost pessary and expulsion of the fetus. RESULTS: The median
      abortion time was 9.0 (1.4-40.5) hours for primigravidae and 7.2 (0-152.5) hours
      for multigravidae. The medium number of gemeprost pessaries to induce abortion
      was two and all except seven women aborted within 24 hours. Significantly more
      abortions occurred before 6, 7 and 8 hours in multigravidae than among
      primigravidae. The induction to abortion interval was also significantly shorter
      for nulliparous than for parous women. Except for one case of heavy bleeding, no
      serious complications occurred. CONCLUSION: The study confirms the efficacy and
      safety of mifepristone, together with gemeprost, for termination of second
      trimester pregnancy when routinely used in the clinic.

PMID- 10949239
TI  - Primary retroperitoneal teratoma.

PMID- 10949240
TI  - Pheochromocytoma in pregnancy--a case report and review of the literature.

PMID- 10949241
TI  - Aggressive vulvar angiomyxoma.

PMID- 10949243
TI  - Post-sterilization molar pregnancy in a 52 year old menopausal woman.

PMID- 10949242
TI  - Successful pregnancy in a case of pituitary dwarfism complicated by diabetes
      insipidus and primary amenorrhea.

PMID- 10949244
TI  - Spontaneous rupture of ovarian arterial aneurysm in the antenatal period.

PMID- 10949246
TI  - What's new for regulations?

PMID- 10949245
TI  - Intravenous iron sucrose in two pregnant women with inflammatory bowel disease
      and severe iron deficiency anemia.

PMID- 10949247
TI  - The 2000 Sievert Lecture--lessons from atomic bomb survivors in Hiroshima and
      Nagasaki.

PMID- 10949248
TI  - Eyeglass lenses for personal radon dosimetry.
AB  - Eyeglass lenses are commonly composed of allyl-diglycol carbonate (CR-39), an
      alpha-particle detecting plastic, thus making such lenses personal radon
      dosimeters. Samples of such lenses have been etched to reveal that radon and
      radon progeny alpha tracks can be seen in abundance, and sensitivities have been
      calibrated in radon chambers as a primary calibration and with a uranium-based
      source of alpha particles as a convenient secondary standard. Natural,
      environmental (fossil) track densities ranged from 3,000 to 25,000 cm(-2) for
      eyeglasses that had been worn for various times from 1 to nearly 5 y. Average
      radon concentrations to which the wearers were exposed are inferred to be in the
      range 20 to 130 Bq m(-3) (0.5 to 3.5 pCi L(-1)). Procedures for consistent,
      meaningful readout are described.

PMID- 10949249
TI  - New approach for dose reconstruction: application to one case of localized
      irradiation with radiological burns.
AB  - When localized accidental irradiation occurs, it is necessary to determine the
      extent to which tissues and vital organs have been damaged, mainly in the
      vicinity of the source. At present, biological markers cannot be used to estimate
      the heterogeneity of the dose distribution. An alternative is to map the absorbed
      dose in the different regions of the body. Using a Monte Carlo calculation code,
      it is possible to simulate the accident while taking into account the specific
      morphology of the irradiated individual and his environment, as well as the
      source characteristics. The calculated values are matched to the clinical signs
      of the lesion, particularly around the rim of the radiation-induced necrosis.
      This technique was applied successfully on two patients who presented very severe
      lesions due to acute localized irradiation after an accident that occurred at
      Lilo (Georgia) in 1996-1997; only the most demonstrative case is presented here.

PMID- 10949250
TI  - 90Sr and 137Cs in environmental samples from Dolon near the Semipalatinsk Nuclear
      Test Site.
AB  - The (90)Sr and (137)Cs activities of soil, plant, and milk samples from the
      village of Dolon, located close to the Semipalatinsk Nuclear Test Site in
      Kazakhstan, were determined. The areal deposition at the nine sampling sites is
      in the range of <500 to 6,100 Bq m(-2) and 300 to 7,900 Bq m-2 for (90)Sr and
      (137)Cs, respectively. Similar values have been reported in the literature. At
      some of the sites both nuclides mainly have remained in the top 6 cm of the soil
      profiles; at others they were partly transported into deeper soil layers since
      the deposition. For most of the samples the (90)Sr yield after destruction of the
      soil matrix is significantly higher than after extracting with 6 M HCl indicating
      that (90)Sr is partly associated with fused silicates. The low mean (90)Sr
      activity concentrations of vegetation samples (14 Bq kg(-1) dw) and milk samples
      (0.05 Bq kg(-1) fw) suggest that this has favorable consequences in terms of
      limiting its bioavailability.

PMID- 10949251
TI  - Ingestion pathway model developed for use with an acute atmospheric dose model at
      the Savannah River Site.
AB  - AXAIRQ is a straight-line Gaussian plume dose model used for prospective accident
      assessment at the Savannah River Site and currently includes the following dose
      pathways: inhalation, ground shine, and plume shine. In the event of an accident,
      another possible pathway for dose would be through ingestion of locally produced
      contaminated foodstuffs. A model, AXINGST, has been developed that would
      incorporate this pathway. Currently available ingestion models were referenced as
      a basis for AXINGST. The model calculates an ingestion dose following an
      atmospheric release of radionuclides and includes site-specific variables where
      applicable. AXINGST estimates tritium vegetation concentrations that are within a
      factor of 20-40 of measured data during previous accidental releases at SRS.

PMID- 10949252
TI  - Derivation of indoor gamma dose rate from high resolution in situ gamma ray
      spectra.
AB  - The dose build up factor B related to the ratio of primary to scattered gamma
      radiation in indoor environment was calculated with Monte Carlo simulations using
      the MCNP code for different indoor geometries and gamma source distributions. The
      main conclusion is that the B factor does not depend strongly on parameters such
      as dimensions of the rooms, the thickness of walls, the density of the building
      materials, and the gamma source geometry. The calculated dose build up factors
      were used within the framework of the full absorption peak analysis method in
      order to deduce the dose rates in air from about 100 indoor in situ gamma
      spectrometry measurements performed at the town of Thessaloniki, Greece. A
      spectral "stripping method," which has been recently developed, was applied to
      the same 100 spectrometry measurements. The results of the dose rates obtained by
      the two methods are compared and discussed.

PMID- 10949254
TI  - Uranium content and leachable fraction of fluorspars.
AB  - Much attention in the radiological health community has recently focused on the
      management and regulation of naturally occurring radioactive materials. Although
      uranium-bearing minerals are present in a variety of fluorspar deposits, their
      potential consideration as naturally occurring radioactive materials has received
      only limited recognition. The uranium content of 28 samples of acid- and cryolite
      grade (>97% CaF2) fluorspar from the National Defense Stockpile was found to
      range from 120 to 24,200 microg kg(-1), with a mean of 2,145 microg kg(-1). As a
      point of comparison, the average concentration of uranium in the upper crust of
      the earth is about 2,500 microg kg(-1). Leachability of this uranium was assessed
      by means of the Toxicity Characteristic Leaching Procedure (TCLP). The TCLP
      extractable fraction ranged from 1 to 98%, with a mean of 24% of the total
      uranium. The typically low concentrations of uranium seen in these materials
      probably reflects the removal of uranium-bearing mineral phases during the
      beneficiation of the crude fluorspar ore to achieve industrial specifications.
      Future NORM studies should examine crude fluorspar ores and flotation tailings.

PMID- 10949253
TI  - Are public dose limits necessary?
AB  - The distinction between practices and interventions in the System of Radiation
      Protection has created a lot of confusion in the population and amongst decision
      makers, especially with regards to the concepts of dose limits and intervention
      levels. The experience gained after the Chernobyl accident indicated that many
      actions taken led to an unnecessarily large expenditure of national resources and
      many instances occurred of contradictory national responses. A major reason was
      the mixture of dose limits for the population, which apply only to exposures from
      practices, and intervention levels, which apply only to protective measures in de
      facto exposure situations. The existing System of Radiation Protection is
      revisited and it is suggested that the System can be revised with no dose limits
      for the public without causing a lower degree of protection of the population.
      With the widespread use of source-related dose constraints and practical
      restrictions on the sources of public exposure from practices, generally
      applicable dose limits are rarely limiting in any practical situation, even if
      dose constraints might, at least in principle, fail to take adequate account of
      the exposures from other practices. Constraints can be expressed as operational
      protection quantities, e.g., nuclide-specific release rates, dose rate at the
      fence of a facility, or nuclide-specific surface contamination density in the
      environment. A revised System of Radiation Protection without public dose limits
      would not cause any reduced protection of the public compared to the existing
      System, and it has a potential for removing much of the confusion with regards to
      application of intervention/action levels. It would also have the potential for
      improving public perception of radiation protection and radiation risks as well
      as for saving vast resources in intervention situations for better application in
      general health care of the public.

PMID- 10949255
TI  - Radioactive waste minimization implications of clinically-indicated
      exsanguination procedures.
AB  - Exsanguination is a method of animal euthanasia approved for use in specific
      circumstances. Animals undergoing exsanguination are fully anesthetized, and the
      blood is removed resulting in hypovolemia. In situations where radioactive
      materials are used as part of a research protocol that remain predominantly
      suspended in the blood, the exsanguination procedure can result in a significant
      lowering of residual radioactivity content. This reduction can greatly affect the
      types of waste management and minimization options that can be subsequently
      applied. In this study, data were collected from 20 rabbits injected with
      approximately 29.6 MBq (0.8 mCi) of tritiated thymidine as part of a percutaneous
      transluminal carotid artery angioplasty study. Residual concentrations of
      radioactivity were consistently reduced by an average of 88%. The reduction was
      very significant in this instance, since the residual activities were below the
      established exemption limit of 1.85 kBq g(-1) (0.05 microCi g(-1)) for disposal
      of these wastes as non-radioactive. Although the exsanguination procedure can
      result in significant waste minimization opportunities in certain circumstances,
      this should not be the rationale for its use. Rather, the method of euthanasia
      should be based exclusively on sound animal care and use principles, and waste
      management strategies should then be made following that decision. Health Phys.
      79(3):291-293; 2000 Key words: waste, low-level; waste management; radiation
      protection; blood

PMID- 10949256
TI  - Hybrid radioassay of multiple radionuclide mixtures in waste solutions by using
      liquid and NaI(Tl) scintillation monitors.
AB  - A new analytical technique for radioactive waste solutions has been developed by
      using a combination of a liquid and a NaI(Tl) scintillation monitor, which
      enables beta-emitter mixtures to be radioassayed using one calculation process
      with the method of least squares. This hybrid system can facilitate the analysis
      of beta-emitter mixtures with very similar liquid scintillation pulse height
      distributions, such as 3H, 51Cr, and 125I. All that is required for the technique
      are sets of quench standards of the nuclides to be analyzed and calibration
      standards for the gamma-emitters. Detection limits for seven nuclides were
      estimated to be about 0.005 Bq mL(-1), which are sufficiently low compared with
      the values of authorized safety guidelines.

PMID- 10949257
TI  - An algorithm for source checking continuous air monitors using radon progeny.
AB  - Department of Energy requirements contained within 10CFR835 require that
      continuous air monitors be periodically checked for operability. The DOE air
      monitoring implementation guide for 10CFR835 allows the use of radon progeny to
      perform the recommended weekly source check. The Defense Waste Processing
      Facility located at the Savannah River Site has demonstrated that, through the
      use of the Hypotheses Concerning Two Means, diurnal change in the radon progeny
      detected by the monitors meets the requirements for weekly source checks. The use
      of the diurnal change in radon progeny has replaced the person-hours expended
      performing direct weekly source checking with an automated system requiring
      minimal person-hour expenditure.

PMID- 10949259
TI  - UNSCEAR 2000. The United Nations Scientific Committee on the Effects of Atomic
      Radiation

PMID- 10949260
TI  - NEA workshop on nuclear fuel cycle safety. Nuclear Energy Agency.

PMID- 10949258
TI  - Age-dependent thyroid doses for iodine.

PMID- 10949261
TI  - Victory for political scientists.

PMID- 10949263
TI  - United States backs soil strategy in fight against global warming

PMID- 10949262
TI  - Tobacco industry vs science.

PMID- 10949264
TI  - Royalty-free rice arrives on the web.

PMID- 10949265
TI  - Spanish biomedical centres face funding uncertainty.

PMID- 10949267
TI  - Microsoft moguls back search for ET intelligence.

PMID- 10949266
TI  - Strong sterling hits European researchers.

PMID- 10949268
TI  - Kansas scientists help to oust creationists.

PMID- 10949269
TI  - From cell phones to brain cells.

PMID- 10949271
TI  - Internet is the new key for restructured film institute

PMID- 10949272
TI  - Antihydrogen: through the looking glass

PMID- 10949270
TI  - German scientists pledge to fight growing xenophobia.

PMID- 10949273
TI  - A mutant mouse menagerie.

PMID- 10949275
TI  - Wise fool left Hussars for career in science admin

PMID- 10949274
TI  - Hawaiian legal action can't save leatherbacks: tackle driftnets instead.

PMID- 10949276
TI  - Environment regulations hinder biotech industry.

PMID- 10949278
TI  - An end to violence

PMID- 10949277
TI  - Boundary disputes.

PMID- 10949280
TI  - Quasicrystals. Electrons in a strange sea

PMID- 10949281
TI  - Benefits of bad telomeres.

PMID- 10949279
TI  - Bacteriorhodopsin--the movie.

PMID- 10949282
TI  - Oceanography. The giant diatom dump.

PMID- 10949283
TI  - Making membranes in bacteria.

PMID- 10949284
TI  - Seafloor spreading. Portrait of a magma chamber

PMID- 10949285
TI  - Chromatin regulation. Formatting genetic text.

PMID- 10949286
TI  - Superconductivity. On the verge of magnetism

PMID- 10949287
TI  - W. David Kingery (1926-2000)

PMID- 10949288
TI  - Predicted vCJD mortality in Great Britain.

PMID- 10949289
TI  - Scrapie in Britain during the BSE years.

PMID- 10949290
TI  - Exercise and reduced muscle mass in starlings.

PMID- 10949291
TI  - Peeling and sharpening multiwall nanotubes

PMID- 10949292
TI  - Superconductivity on the border of itinerant-electron ferromagnetism in UGe2
AB  - The absence of simple examples of superconductivity adjoining itinerant-electron
      ferromagnetism in the phase diagram has for many years cast doubt on the validity
      of conventional models of magnetically mediated superconductivity. On closer
      examination, however, very few systems have been studied in the extreme
      conditions of purity, proximity to the ferromagnetic state and very low
      temperatures required to test the theory definitively. Here we report the
      observation of superconductivity on the border of ferromagnetism in a pure
      system, UGe2, which is known to be qualitatively similar to the classic d
      electron ferromagnets. The superconductivity that we observe below 1 K, in a
      limited pressure range on the border of ferromagnetism, seems to arise from the
      same electrons that produce band magnetism. In this case, superconductivity is
      most naturally understood in terms of magnetic as opposed to lattice
      interactions, and by a spin-triplet rather than the spin-singlet pairing normally
      associated with nearly antiferromagnetic metals.

PMID- 10949294
TI  - Evaporation in the young solar nebula as the origin of 'just-right' melting of
      chondrules
AB  - Chondrules are millimetre-sized, solidified melt spherules formed in the solar
      nebula by an early widespread heating event of uncertain nature. They were
      accreted into chondritic asteroids, which formed about 4.56 billion years ago and
      have not experienced melting or differentiation since that time. Chondrules have
      diverse chemical compositions, corresponding to liquidus temperatures in the
      range 1,350-1,800 degrees C. Most chondrules, however, show porphyritic textures
      (consisting of large crystals in a distinctly finer grained or glassy matrix),
      indicative of melting within the narrow range 0-50 degrees C below the liquidus.
      This suggests an unusual heating mechanism for chondrule precursors, which would
      raise each individual chondrule to just the right temperature (particular to
      individual bulk composition) in order to form porphyritic textures. Here we
      report the results of isothermal melting of a chondritic composition at nebular
      pressures. Our results suggest that evaporation stabilizes porphyritic textures
      over a wider range of temperatures below the liquidus (about 200 degrees C) than
      previously believed, thus removing the need for individual chondrule temperature
      buffering. In addition, we show that evaporation explains many chondrule bulk and
      mineral compositions that have hitherto been difficult to understand.

PMID- 10949293
TI  - Regulation of chromatin structure by site-specific histone H3 methyltransferases.
AB  - The organization of chromatin into higher-order structures influences chromosome
      function and epigenetic gene regulation. Higher-order chromatin has been proposed
      to be nucleated by the covalent modification of histone tails and the subsequent
      establishment of chromosomal subdomains by non-histone modifier factors. Here we
      show that human SUV39H1 and murine Suv39h1--mammalian homologues of Drosophila
      Su(var)3-9 and of Schizosaccharomyces pombe clr4--encode histone H3-specific
      methyltransferases that selectively methylate lysine 9 of the amino terminus of
      histone H3 in vitro. We mapped the catalytic motif to the evolutionarily
      conserved SET domain, which requires adjacent cysteine-rich regions to confer
      histone methyltransferase activity. Methylation of lysine 9 interferes with
      phosphorylation of serine 10, but is also influenced by pre-existing
      modifications in the amino terminus of H3. In vivo, deregulated SUV39H1 or
      disrupted Suv39h activity modulate H3 serine 10 phosphorylation in native
      chromatin and induce aberrant mitotic divisions. Our data reveal a functional
      interdependence of site-specific H3 tail modifications and suggest a dynamic
      mechanism for the regulation of higher-order chromatin.

PMID- 10949295
TI  - Quasicrystalline valence bands in decagonal AlNiCo
AB  - Quasicrystals are metallic alloys that possess perfect long-range structural
      order, in spite of the fact that their rotational symmetries are incompatible
      with long-range periodicity. The exotic structural properties of this class of
      materials are accompanied by physical properties that are unexpected for metallic
      alloys. Considerable progress in resolving the geometric structures of
      quasicrystals has been made using X-ray and neutron diffraction, and concepts
      such as the quasi-unit-cell model have provided theoretical insights. But the
      basic properties of the valence electronic states--whether they are extended as
      in periodic crystals or localized as in amorphous materials--are still largely
      unresolved. Here we investigate the electronic bandstructure of quasicrystals
      through angle-resolved photoemission experiments on decagonal Al71.8Ni14.8Co13.4.
      We find that the s-p and d states exhibit band-like behaviour with the symmetry
      of the quasiperiodic lattice, and that the Fermi level is crossed by dispersing d
      bands. The observation of free-electron-like bands, distributed in momentum space
      according to the surface diffraction pattern, suggests that the electronic states
      are not dominated by localization.

PMID- 10949296
TI  - A DNA-fuelled molecular machine made of DNA.
AB  - Molecular recognition between complementary strands of DNA allows construction on
      a nanometre length scale. For example, DNA tags may be used to organize the
      assembly of colloidal particles, and DNA templates can direct the growth of
      semiconductor nanocrystals and metal wires. As a structural material in its own
      right, DNA can be used to make ordered static arrays of tiles, linked rings and
      polyhedra. The construction of active devices is also possible--for example, a
      nanomechanical switch, whose conformation is changed by inducing a transition in
      the chirality of the DNA double helix. Melting of chemically modified DNA has
      been induced by optical absorption, and conformational changes caused by the
      binding of oligonucleotides or other small groups have been shown to change the
      enzymatic activity of ribozymes. Here we report the construction of a DNA machine
      in which the DNA is used not only as a structural material, but also as 'fuel'.
      The machine, made from three strands of DNA, has the form of a pair of tweezers.
      It may be closed and opened by addition of auxiliary strands of 'fuel' DNA; each
      cycle produces a duplex DNA waste product.

PMID- 10949297
TI  - Influencing intramolecular motion with an alternating electric field
AB  - Analogues of mechanical devices that operate on the molecular level, such as
      shuttles, brakes, ratchets, turnstiles and unidirectional spinning motors, are
      current targets of both synthetic chemistry and nanotechnology. These structures
      are designed to restrict the degrees of freedom of submolecular components such
      that they can only move with respect to each other in a predetermined manner,
      ideally under the influence of some external stimuli. Alternating-current (a.c.)
      electric fields are commonly used to probe electronic structure, but can also
      change the orientation of molecules (a phenomenon exploited in liquid crystal
      displays), or interact with large-scale molecular motions, such as the backbone
      fluctuations of semi-rigid polymers. Here we show that modest a.c. fields can be
      used to monitor and influence the relative motion within certain rotaxanes,
      molecules comprising a ring that rotates around a linear 'thread' carrying bulky
      'stoppers' at each end. We observe strong birefringence at frequencies that
      correspond to the rate at which the molecular ring pirouettes about the thread,
      with the frequency of maximum birefringence, and by inference also the rate of
      ring pirouetting giving rise to it, changing as the electric field strength is
      varied. Computer simulations and nuclear magnetic resonance spectroscopy show the
      ring rotation to be the only dynamic process occurring on a timescale
      corresponding to the frequency of maximum birefringence, thus confirming that
      mechanical motion within the rotaxanes can be addressed, and to some extent
      controlled, by oscillating electric fields.

PMID- 10949298
TI  - Water activity as the determinant for homogeneous ice nucleation in aqueous
      solutions
AB  - The unique properties of water in the supercooled (metastable) state are not
      fully understood. In particular, the effects of solutes and mechanical pressure
      on the kinetics of the liquid-to-solid phase transition of supercooled water and
      aqueous solutions to ice have remained unresolved. Here we show from experimental
      data that the homogeneous nucleation of ice from supercooled aqueous solutions is
      independent of the nature of the solute, but depends only on the water activity
      of the solution--that is, the ratio between the water vapour pressures of the
      solution and of pure water under the same conditions. In addition, we show that
      the presence of solutes and the application of pressure have a very similar
      effect on ice nucleation. We present a thermodynamic theory for homogeneous ice
      nucleation, which expresses the nucleation rate coefficient as a function of
      water activity and pressure. Recent observations from clouds containing ice are
      in good agreement with our theory and our results should help to overcome one of
      the main weaknesses of numerical models of the atmosphere, the formulation of
      cloud processes.

PMID- 10949300
TI  - Fine structure of bone in dinosaurs, birds and mammals.
AB  - After observation of detailed structural evidence for the origin of birds from
      dinosaurs, and in light of evidence that dinosaur bone tissue resembles the
      histology in mammals, the histology of bone has become one of the focal points in
      discussions of the physiology of dinosaurs and Mesozoic birds. Most of this
      microstructural information has focused on features related to the vascular
      organization and the amount of remodelled bone around vascular canals. However,
      the finer structures have received less attention, although differences in such
      structures have been observed among modern vertebrates. Here we present evidence
      that canaliculi--the submicrometre-sized channels that interconnect bone cells
      and vascular canals--and the collagen fibre bundles in bone are differently
      organized among certain dinosaur lineages. Ornithomimid dinosaurs are more like
      birds than mammals in these features. In canalicular structure, and to some
      extent in fibre bundle arrangement, ornithischian dinosaurs are more like
      mammals. These differences in both canalicular and lamellar structure are
      probably linked to differences in the process and rate of bone formation.

PMID- 10949299
TI  - Evidence from three-dimensional seismic reflectivity images for enhanced melt
      supply beneath mid-ocean-ridge discontinuities
AB  - Quantifying the melt distribution and crustal structure across ridge-axis
      discontinuities is essential for understanding the relationship between magmatic,
      tectonic and petrologic segmentation of mid-ocean-ridge spreading centres. The
      geometry and continuity of magma bodies beneath features such as overlapping
      spreading centres can strongly influence the composition of erupted lavas and may
      give insight into the underlying pattern of mantle flow. Here we present three
      dimensional images of seismic reflectivity beneath a mid-ocean ridge to
      investigate the nature of melt distribution across a ridge-axis discontinuity.
      Reflectivity slices through the 9 degrees 03' N overlapping spreading centre on
      East Pacific Rise suggest that it has a robust magma supply, with melt bodies
      underlying both limbs and ponding of melt beneath large areas of the overlap
      basin. The geometry of melt distribution beneath this offset is inconsistent with
      large-scale, crustal redistribution of melt away from centres of upwelling. The
      complex distribution of melt seems instead to be caused by a combination of
      vertical melt transport from the underlying mantle and subsequent focusing of
      melt beneath a magma freezing boundary in the mid-crust.

PMID- 10949301
TI  - Unexpectedly similar rates of nucleotide substitution found in male and female
      hominids.
AB  - In 1947, it was suggested that, in humans, the mutation rate is dramatically
      higher in the male germ line than in the female germ line. This hypothesis has
      been supported by the observation that, among primates, Y-linked genes evolved
      more rapidly than homologous X-linked genes. Based on these evolutionary studies,
      the ratio (alpha(m)) of male to female mutation rates in primates was estimated
      to be about 5. However, selection could have skewed sequence evolution in introns
      and exons. In addition, some of the X-Y gene pairs studied lie within chromosomal
      regions with substantially divergent nucleotide sequences. Here we directly
      compare human X and Y sequences within a large region with no known genes. Here
      the two chromosomes are 99% identical, and X-Y divergence began only three or
      four million years ago, during hominid evolution. In apes, homologous sequences
      exist only on the X chromosome. We sequenced and compared 38.6 kb of this region
      from human X, human Y, chimpanzee X and gorilla X chromosomes. We calculated
      alpha(m) to be 1.7 (95% confidence interval 1.15-2.87), significantly lower than
      previous estimates in primates. We infer that, in humans and their immediate
      ancestors, male and female mutation rates were far more similar than previously
      supposed.

PMID- 10949302
TI  - Evolvability of an RNA virus is determined by its mutational neighbourhood.
AB  - The ubiquity of mechanisms that generate genetic variation has spurred arguments
      that evolvability, the ability to generate adaptive variation, has itself evolved
      in response to natural selection. The high mutation rate of RNA viruses is
      postulated to be an adaptation for evolvability, but the paradox is that whereas
      some RNA viruses evolve at high rates, others are highly stable. Here we show
      that evolvability in the RNA bacteriophage phi6 is also determined by the
      accessibility of advantageous genotypes within the mutational neighbourhood (the
      set of mutants one or a few mutational steps away). We found that two phi6
      populations that were derived from a single ancestral phage repeatedly evolved at
      different rates and toward different fitness maxima. Fitness measurements of
      individual phages showed that the fitness distribution of mutants differed
      between the two populations. Whereas population A, which evolved toward a higher
      maximum, had a distribution that contained many advantageous mutants, population
      B, which evolved toward a lower maximum, had a distribution that contained only
      deleterious mutants. We interpret these distributions to measure the fitness
      effects of genotypes that are mutationally available to the two populations.
      Thus, the evolvability of phi6 is constrained by the distribution of its
      mutational neighbours, despite the fact that this phage has the characteristic
      high mutation rate of RNA viruses.

PMID- 10949303
TI  - Behaviourally driven gene expression reveals song nuclei in hummingbird brain.
AB  - Hummingbirds have developed a wealth of intriguing features, such as backwards
      flight, ultraviolet vision, extremely high metabolic rates, nocturnal
      hibernation, high brain-to-body size ratio and a remarkable species-specific
      diversity of vocalizations. Like humans, they have also developed the rare trait
      of vocal learning, this being the ability to acquire vocalizations through
      imitation rather than instinct. Here we show, using behaviourally driven gene
      expression in freely ranging tropical animals, that the forebrain of hummingbirds
      contains seven discrete structures that are active during singing, providing the
      first anatomical and functional demonstration of vocal nuclei in hummingbirds.
      These structures are strikingly similar to seven forebrain regions that are
      involved in vocal learning and production in songbirds and parrots--the only
      other avian orders known to be vocal learners. This similarity is surprising, as
      songbirds, parrots and hummingbirds are thought to have evolved vocal learning
      and associated brain structures independently, and it indicates that strong
      constraints may influence the evolution of forebrain vocal nuclei.

PMID- 10949304
TI  - NO is necessary and sufficient for egg activation at fertilization.
AB  - The early steps that lead to the rise in calcium and egg activation at
      fertilization are unknown but of great interest--particularly with the advent of
      in vitro fertilization techniques for treating male infertility and whole-animal
      cloning by nuclear transfer. This calcium rise is required for egg activation and
      the subsequent events of development in eggs of all species. Injection of intact
      sperm or sperm extracts can activate eggs, suggesting that sperm-derived factors
      may be involved. Here we show that nitric oxide synthase is present at high
      concentration and active in sperm after activation by the acrosome reaction. An
      increase in nitrosation within eggs is evident seconds after insemination and
      precedes the calcium pulse of fertilization. Microinjection of nitric oxide
      donors or recombinant nitric oxide synthase recapitulates events of egg
      activation, whereas prior injection of oxyhaemoglobin, a physiological nitric
      oxide scavenger, prevents egg activation after fertilization. We conclude that
      nitric oxide synthase and nitric-oxide-related bioactivity satisfy the primary
      criteria of an egg activator: they are present in an appropriate place, active at
      an appropriate time, and are necessary and sufficient for successful
      fertilization.

PMID- 10949305
TI  - YidC mediates membrane protein insertion in bacteria.
AB  - The basic machinery for the translocation of proteins into or across membranes is
      remarkably conserved from Escherichia coli to humans. In eukaryotes, proteins are
      inserted into the endoplasmic reticulum using the signal recognition particle
      (SRP) and the SRP receptor, as well as the integral membrane Sec61 trimeric
      complex (composed of alpha, beta and gamma subunits). In bacteria, most proteins
      are inserted by a related pathway that includes the SRP homologue Ffh, the SRP
      receptor FtsY, and the SecYEG trimeric complex, where Y and E are related to the
      Sec61 alpha and gamma subunits, respectively. Proteins in bacteria that exhibit
      no dependence on the Sec translocase were previously thought to insert into the
      membrane directly without the aid of a protein machinery. Here we show that
      membrane insertion of two Sec-independent proteins requires YidC. YidC is
      essential for E. coli viability and homologues are present in mitochondria and
      chloroplasts. Depletion of YidC also interferes with insertion of Sec-dependent
      membrane proteins, but it has only a minor effect on the export of secretory
      proteins. These results provide evidence for an additional component of the
      translocation machinery that is specialized for the integration of membrane
      proteins.

PMID- 10949306
TI  - Telomere dysfunction promotes non-reciprocal translocations and epithelial
      cancers in mice.
AB  - Aged humans sustain a high rate of epithelial cancers such as carcinomas of the
      breast and colon, whereas mice carrying common tumour suppressor gene mutations
      typically develop soft tissue sarcomas and lymphomas. Among the many factors that
      may contribute to this species variance are differences in telomere length and
      regulation. Telomeres comprise the nucleoprotein complexes that cap the ends of
      eukaryotic chromosomes and are maintained by the reverse transcriptase,
      telomerase. In human cells, insufficient levels of telomerase lead to telomere
      attrition with cell division in culture and possibly with ageing and
      tumorigenesis in vivo. In contrast, critical reduction in telomere length is not
      observed in the mouse owing to promiscuous telomerase expression and long
      telomeres. Here we provide evidence that telomere attrition in ageing telomerase
      deficient p53 mutant mice promotes the development of epithelial cancers by a
      process of fusion-bridge breakage that leads to the formation of complex non
      reciprocal translocations--a classical cytogenetic feature of human carcinomas.
      Our data suggest a model in which telomere dysfunction brought about by continual
      epithelial renewal during life generates the massive ploidy changes associated
      with the development of epithelial cancers.

PMID- 10949307
TI  - Helix deformation is coupled to vectorial proton transport in the photocycle of
      bacteriorhodopsin.
AB  - A wide variety of mechanisms are used to generate a proton-motive potential
      across cell membranes, a function lying at the heart of bioenergetics.
      Bacteriorhodopsin, the simplest known proton pump, provides a paradigm for
      understanding this process. Here we report, at 2.1 A resolution, the structural
      changes in bacteriorhodopsin immediately preceding the primary proton transfer
      event in its photocycle. The early structural rearrangements propagate from the
      protein's core towards the extracellular surface, disrupting the network of
      hydrogen-bonded water molecules that stabilizes helix C in the ground state.
      Concomitantly, a bend of this helix enables the negatively charged primary proton
      acceptor, Asp 85, to approach closer to the positively charged primary proton
      donor, the Schiff base. The primary proton transfer event would then neutralize
      these two groups, cancelling their electrostatic attraction and facilitating a
      relaxation of helix C to a less strained geometry. Reprotonation of the Schiff
      base by Asp 85 would thereby be impeded, ensuring vectorial proton transport.
      Structural rearrangements also occur near the protein's surface, aiding proton
      release to the extracellular medium.

PMID- 10949308
TI  - Structural alterations for proton translocation in the M state of wild-type
      bacteriorhodopsin.
AB  - The transport of protons across membranes is an important process in cellular
      bioenergetics. The light-driven proton pump bacteriorhodopsin is the best
      characterized protein providing this function. Photon energy is absorbed by the
      chromophore retinal, covalently bound to Lys 216 via a protonated Schiff base.
      The light-induced all-trans to 13-cis isomerization of the retinal results in
      deprotonation of the Schiff base followed by alterations in protonatable groups
      within bacteriorhodopsin. The changed force field induces changes, even in the
      tertiary structure, which are necessary for proton pumping. The recent report of
      a high-resolution X-ray crystal structure for the late M intermediate of a mutant
      bacteriorhopsin (with Asp 96-->Asn) displays the structure of a proton pathway
      highly disturbed by the mutation. To observe an unperturbed proton pathway, we
      determined the structure of the late M intermediate of wild-type
      bacteriorhodopsin (2.25 A resolution). The cytoplasmic side of our M2 structure
      shows a water net that allows proton transfer from the proton donor group Asp 96
      towards the Schiff base. An enlarged cavity system above Asp 96 is observed,
      which facilitates the de- and reprotonation of this group by fluctuating water
      molecules in the last part of the cycle.

PMID- 10949309
TI  - Molecular mechanism of vectorial proton translocation by bacteriorhodopsin.
AB  - Bacteriorhodopsin, a membrane protein with a relative molecular mass of 27,000,
      is a light driven pump which transports protons across the cell membrane of the
      halophilic organism Halobacterium salinarum. The chromophore retinal is
      covalently attached to the protein via a protonated Schiff base. Upon
      illumination, retinal is isomerized. The Schiff base then releases a proton to
      the extracellular medium, and is subsequently reprotonated from the cytoplasm. An
      atomic model for bacteriorhodopsin was first determined by Henderson et al, and
      has been confirmed and extended by work in a number of laboratories in the last
      few years. Here we present an atomic model for structural changes involved in the
      vectorial, light-driven transport of protons by bacteriorhodopsin. A 'switch'
      mechanism ensures the vectorial nature of pumping. First, retinal unbends,
      triggered by loss of the Schiff base proton, and second, a protein conformational
      change occurs. This conformational change, which we have determined by electron
      crystallography at atomic (3.2 A in-plane and 3.6 A vertical) resolution, is
      largely localized to helices F and G, and provides an 'opening' of the protein to
      protons on the cytoplasmic side of the membrane.

PMID- 10949310
TI  - Rapid degradation of ferulic acid via 4-vinylguaiacol and vanillin by a newly
      isolated strain of bacillus coagulans.
AB  - A new strain Bacillus coagulans BK07 was isolated from decomposed wood-bark,
      based on its ability to grow on ferulic acid as a sole carbon source. This strain
      rapidly decarboxylated ferulic acid to 4-vinylguaiacol, which was immediately
      converted to vanillin and then oxidized to vanillic acid. Vanillic acid was
      further demethylated to protocatechuic acid. Above 95% substrate degradation was
      obtained within 7 h of growth on ferulic acid medium, which is the shortest
      period of time reported to date. The major degradation products, was isolated and
      identified by thin-layer chromatography, high performance liquid chromatography
      and 1H-nuclear magnetic resonance spectroscopy were 4-vinylguaiacol, vanillin,
      vanillic acid and protocatechuic acid.

PMID- 10949311
TI  - Analysis and description of the evolution of alginate immobilised cells systems.
AB  - Different immobilised cells models, including very simple ones, can be useful in
      the fitting of experimental results. However, goodness or the ability to
      extrapolate results needs to be in accordance with basic observations and these
      will also suggest models to be proposed. In this paper, observations of calcium
      alginate/bacteria systems are used to show the ability of basic models to fit
      classic observations, as well as how new observations, in this case from
      electronic microscopy, oblige us to think about more complex mechanisms and
      mathematical treatments. Nevertheless it is not only important to discuss the
      model type, but also the type of kinetics assumed in the interior of the beads,
      as well as the internal structure, the boundary conditions related to bead
      shredding and cell escape and finally, geometrical effects.

PMID- 10949312
TI  - Hydantoin racemase from Arthrobacter aurescens DSM 3747: heterologous expression,
      purification and characterization.
AB  - In Arthrobacter aurescens DSM 3747 three enzymes are involved in the complete
      conversion of slowly racemizing 5'-monosubstituted D,L-hydantoins to L-amino
      acids, a stereoselective hydantoinase, a stereospecific L-N-carbamoylase and a
      hydantoin racemase. The gene encoding the hydantoin racemase, designated hyuA,
      was identified upstream of the previously described L-N-carbamoylase gene in the
      plasmid pAW16 containing genomic DNA of A. aurescens. The gene hyuA which encodes
      a polypeptide of 25.1 kDa, was expressed in Escherichia coli and the recombinant
      protein purified to homogeneity and further characterized. The optimal condition
      for racemase activity were pH 8.5 and 55 degrees C with L-5-benzylhydantoin as
      substrate. The enzyme was completely inhibited by HgCL2 and iodoacetamide and
      stimulated by addition of dithiothreitol. No effect on enzyme activity was seen
      with EDTA. The enzyme showed preference for hydantoins with arylalkyl side
      chains. Kinetic studies revealed substrate inhibition towards the aliphatic
      substrate L-5-methylthioethylhydantoin. Enzymatic racemization of D-5
      indolylmethylenehydantoin in D2O and NMR analysis showed that the hydrogen at the
      chiral center of the hydantoin is exchanged against solvent deuterium during the
      racemization.

PMID- 10949313
TI  - Elimination and detoxification of softwood extractives by white-rot fungi.
AB  - The ability of several white-rot fungal strains to remove and detoxify acetone
      extractives (pitch or resin) in Scots pine sapwood was investigated in stationary
      laboratory batch assays. Fungal pretreatment provided up to 62% total pitch
      reduction and significant decreases in pitch toxicity. The best strains were
      Bjerkandera sp. strain Stereum hirsutum and Trametes versicolor that eliminated
      over 93% of the problematic triglyceride fraction and 58-87% of other lipophilic
      extractive classes in only 2 weeks. Fungal removal of the wood extractives was
      accompanied by a 7.4-16.9-fold decrease in their inhibitory effect, as determined
      in the Microtox bioassay. Wood pretreatment by Bjerkandera sp. and T. versicolor
      caused limited losses of woody mass (less than 4% in 4 weeks); whereas S.
      hirsutum led to somewhat higher mass losses (7% in 4 weeks). These results
      indicate the potential of white rot fungi to control pitch deposition problems in
      pulping and to reduce the aquatic toxicity caused by naturally-occurring
      lipophilic extractives in forest industry effluents.

PMID- 10949314
TI  - Influence of lignin and its degradation products on enzymatic hydrolysis of
      xylan.
AB  - The influence of lignin, lignin model compounds, and black liquor from the kraft
      pulping process on the hydrolysis of xylan by xylanase was investigated. Addition
      of vanillic acid, acetovanillone, and protocatechuic acid increased the rate of
      hydrolysis of xylan by as much as 18-50% at low concentrations, but reached
      maxima at about 0.05% concentration. Addition of vanillin caused a 15%
      improvement in xylan hydrolysis, while addition of guaiacol more than doubled the
      hydrolysis rate. Increasing concentrations of either lignin or black liquor also
      increased the hydrolysis rate of xylan. Circular dichroism spectroscopy indicated
      a change in the structure of xylanase in the presence of black liquor.

PMID- 10949315
TI  - Abiotic and enzymatic degradation of wheat straw cell wall: a biochemical and
      ultrastructural investigation.
AB  - The action of an abiotic lignin oxidant and a diffusible xylanase on wheat straw
      was studied and characterized at the levels of the molecular structures by
      chemical analysis and of the cell wall ultrastructure by transmission electron
      microscopy. While distinct chemical changes in the target polymers were observed
      when each system was used separately, a combination of the two types of catalysts
      did not significantly increase either lignin oxidation or hemicellulose
      hydrolysis. Microscopic observations however revealed that the supramolecular
      organization of the cell wall polymers was significantly altered. This suggests
      that the abiotic Mn-oxalate complex and the xylanase cooperate in modifying the
      cell wall architecture, without noticeably enhancing the degradation of the
      constitutive polymers.

PMID- 10949316
TI  - Improved production and function of llama heavy chain antibody fragments by
      molecular evolution.
AB  - The aim of this study was to improve production level of llama heavy chain
      antibody fragments (V(HH)) in Saccharomyces cerevisiae while retaining functional
      characteristics. For this purpose, the DNA shuffling technique was used on llama
      V(HH) fragments specific for the azo-dye reactive red-6. In the DNA shuffling
      process, three parental llama V(HH) with high amino acid sequence identity with
      significant differences in production and functional characteristics were used.
      From these parental sequences, a S. cerevisiae library was created and 16 antigen
      specific shuffled V(HH) fragments were selected. We found that these shuffled
      V(HH) fragments were, (i) unique in sequence; (ii) composed of two or three
      parental sequences; (iii) in three V(HH)s point mutations occurred; and (iv)
      antigen specificity was not changed. The four highest producers in the yeast S.
      cerevisiae were selected and production, affinity, and antigen binding at 90
      degrees C were compared with parental V(HH)s. One shuffled V(HH) was enhanced
      both in production (3.4-fold) and affinity (four-fold). A second shuffled V(HH)
      displayed increased production (1.9-fold), and improved stability (2.4-fold) in
      antigen binding at 90 degrees C. Structural analysis suggested that improved
      antigen binding is associated with the A24 --> V24 substitution, which reduces
      the size of the hydrophobic pit at the llama V(HH) surface. We demonstrate that
      it is possible to improve desired characteristics of the same V(HH) fragment
      simultaneously using DNA shuffling. Finally, this is one of the first examples of
      DNA shuffling improving temperature stability of an antibody fragment.

PMID- 10949317
TI  - Repeated-batch production of pigments by immobilised Monascus purpureus.
AB  - Extracellular pigment production by immobilised Monascus purpureus C322 has been
      studied in repeated-batch processes using different immobilising carriers such as
      Ca-alginate, polyurethane sponge, active carbon and pearlite. With Ca-alginate,
      pigment production was maximum (30.5 UA470 as process mean production, three
      batches) while the cell leakage was negligible (0.4 g 1(-1) free biomass) and the
      bead mechanical stability good; with this carrier, an extended repeated-batch
      fermentation (nine batches, 55 days) was carried out: the process pigment
      productivity was 3.87 UA470 day(-1).

PMID- 10949318
TI  - Analysis of the chiB gene of Serratia liquefaciens.
AB  - A 4.6-kb EcoRI/BglII fragment of Serratia liquefaciens genomic DNA has been
      sequenced and within this fragment the chiB gene has been identified and
      characterized. The chiB ORF encodes a polypeptide with a deduced molecular mass
      of 52-kDa and the translational product in vitro has chitinase, but not
      chitobiase activity. Alignment of the predicted Chib 499 amino acid sequence
      indicated a chitin-binding and a catalytic domain that shares homology to the
      chitinase family 18 domain, to the Chib polypeptide of Serratia marcescens
      QMB1466 (93.6%), a human chitinase and several bacterial chitinases. This chiB
      gene sequence transcription/translation in Escherichia coli may be blocked by a
      RNA folding mechanism thus controlling the chitin utilization regulon in S.
      liquefaciens.

PMID- 10949319
TI  - Partnering for better lung health: improving tobacco and tuberculosis control.
AB  - Tuberculosis and tobacco together constitute a considerable threat to global
      health. Several recent initiatives by non-governmental organisations and the
      World Health Organization have highlighted the need for concerted approaches to
      lung health that require addressing both of these major threats. However, the
      emphasis has been on independent effects on health and on independent strategies
      to control. There is a clear case for closer partnering between researchers,
      service providers and policy makers in addressing tuberculosis and tobacco. This
      is based upon growing epidemiological and laboratory evidence that indicate that
      tobacco is a risk factor for tuberculosis and for death from tuberculosis.
      Despite the fact that a very high percentage of tuberculosis patients smoke in
      all settings for which data are available, opportunities to treat tobacco
      dependence in such patients are under-utilised. This paper will recommend areas
      that require research, policy development and immediate action.

PMID- 10949320
TI  - Smoking and eight-year mortality in an elderly cohort.
AB  - SETTING: The increasing numbers of elderly people highlight the question of
      smoking effects in this age group. OBJECTIVE: To investigate whether there is a
      relationship between smoking and 8-year mortality in a representative elderly
      cohort aged 65 years and over, residing in the department of Gironde, in the
      south-west of France. METHODS: Data were collected by a questionnaire
      administered during home visits. Every death was systematically recorded during
      the 8-year follow-up. RESULTS: The 2786 (99.8%) subjects included in the study
      were categorised into current smokers, former smokers and never smokers.
      Mortality was higher (P < 0.0001) in men (39.6%) than in women (29.4%). In men,
      the risk of mortality was higher (P = 0.01) among current (44.5%) and former
      smokers (41.4%) than in never smokers (32.5%). The risks were similar in never
      smokers and former smokers who had stopped more than 20 years previously. Tobacco
      consumption in pack-years was higher (P = 0.02) in those people who died during
      the follow-up period than in those who were still alive. Mortality due to
      respiratory disease (P = 0.008) and lung cancer (P < 0.0001) was significantly
      higher in current smokers than in former and never smokers. Adjusting for
      potential confounding factors, smoking remains significantly associated with
      mortality both in current (relative risk [RR] = 1.7, P < 0.001) and former
      smokers (RR = 1.3, P = 0.004). CONCLUSION: These results confirm the consequences
      of smoking even in the elderly, and raise the question of smoking prevention
      after 65 years of age.

PMID- 10949321
TI  - Factors associated with an increased case-fatality rate in HIV-infected and non
      infected South African gold miners with pulmonary tuberculosis.
AB  - SETTING: A gold mining company in the Free State Province, South Africa. AIM AND
      DESIGN: A retrospective cohort study to investigate factors associated with an
      increased case-fatality rate (CFR) at 6 months in human immunodeficiency virus
      (HIV) positive and negative tuberculosis (TB) patients. RESULTS: Between April
      1993 and March 1997, there were 2236 men with culture-confirmed pulmonary TB in
      whom HIV status and treatment outcome were known. The overall CFR within the
      first 6 months of therapy was low (3.6%). After adjusting for confounding
      factors, HIV infection (OR 15.0, 95%CI 7.4-30.6), self-presentation compared to
      detection by the active radiological screening programme (OR 5.6, 95%CI 2.6-12.2)
      and presence of silicosis (OR 3.0, 95%CI 1.4-6.3) were significantly associated
      with an increased CFR. Opportunistic infections accounted for 56.2% (36/64) of
      deaths in HIV-positive men. Cryptococcal disease accounted for 75% (27/36) of
      deaths from opportunistic infections. CONCLUSION: HIV infection and silicosis are
      both powerful risk factors for TB and are associated with an increased risk of
      death. Strategies aimed at reducing these two risk factors within the workforce
      could reduce TB incidence and mortality. In settings with functional DOTS
      programmes and sufficient resources, expanding the DOTS programme to include
      active case detection should be explored as a means of reducing TB prevalence and
      mortality.

PMID- 10949323
TI  - Trends in the prevalence of infection with mycobacterium tuberculosis in Korea
      from 1965 to 1995: an analysis of seven surveys by mixture models.
AB  - SETTING: Korea. OBJECTIVE: Estimation of the prevalence of tuberculous infection
      from tuberculin skin test surveys can be difficult if cross-reactions resulting
      from infection with environmental mycobacteria outweigh reactions resulting from
      tuberculous infection. Mixture analysis was thus chosen as a novel approach for
      estimating the prevalence of tuberculous infection in Korea. DESIGN: Seven
      tuberculin skin test surveys conducted between 1965 and 1995 were analyzed by
      mixture models, a statistical methodology used either to estimate a prevalence or
      to classify individuals into predefined homogeneous sub-populations. A Bayesian
      approach including prior information on component distributions was taken. The
      final model was selected based on the fit to observed values, and the analysis
      was therefore stratified by sex and year of survey and included age as a
      covariate. RESULTS: The results showed a large decrease in tuberculous infection
      in the population below 30 years of age: among 10- to 14-year-old boys (girls),
      infection prevalence decreased from 74.5% (67.9%) in 1965 to 16.5% (16.9%) in
      1995. Additionally, the mean induration for individuals with tuberculous
      infection decreased by 2mm between 1965 and 1995, indicating a changing
      sensitivity of tuberculin over time. CONCLUSIONS: Mixture analysis is a promising
      approach for determining the prevalence of tuberculous infection in the presence
      of substantial interference from infection with environmental mycobacteria and
      changing tuberculin reaction sizes over time.

PMID- 10949322
TI  - The epidemiology of tuberculosis in patients with AIDS in Puerto Rico: morbidity
      and survival, 1981-1998.
AB  - SETTING: Puerto Rico. OBJECTIVE: To describe the characteristics and survival
      experience of AIDS patients with tuberculosis (TB) from 1981 through 1998.
      DESIGN: A population based study using the AIDS Surveillance System, including
      survival analysis. RESULTS: During the period studied, 1000 AIDS cases were
      reported with TB, representing 4.3% of total cases. Of these, males accounted for
      82.1%, and 84% were diagnosed with pulmonary TB. Approximately 71% of the cases
      were reported as having died. AIDS cases who were intravenous drug users (IDU)
      accounted for 63.7% of the cases. The median survival of AIDS/TB cases was 21.4
      months, and did not differ by sex or TB site (P > 0.05). IDUs with TB had a
      longer survival than IDUs with other AIDS-defining conditions; however, AIDS/TB
      cases with a CD4 count < 200/mm3 had a poorer survival (23.4 months) than those
      with a count of > or = 200/mm3 (47.9 months). CONCLUSIONS: The overall prevalence
      of TB in AIDS patients in Puerto Rico is low compared with other countries. As in
      other studies, the variable that explained poorer survival among AIDS/TB cases
      was the CD4+ lymphocyte count. Further prospective studies regarding survival in
      the Hispanic population are needed to confirm these findings.

PMID- 10949324
TI  - Anti-tuberculosis treatment in private pharmacies, Kathmandu Valley, Nepal.
AB  - SETTING: Urban municipality of 150000 citizens in Kathmandu Valley, Nepal.
      OBJECTIVE: To determine 1) the perceptions among private pharmacists of
      characteristics of tuberculosis (TB) patients visiting private pharmacies in the
      area, 2) the sales of different anti-tuberculosis drugs, and 3) the interaction
      between private health providers and pharmacists. DESIGN: Between January and
      April 1998, semi-structured interviews were conducted with 98% (49/50) of the
      private drug-retailers in the area. RESULTS: Thirty-two (65%) pharmacies had sold
      anti-TB drugs during the last month. Forty-three (88%) said that most TB patients
      were of low socio-economic status and rarely bought drugs for more than a week at
      a time. Only eight (16%) reported that TB patients usually returned to buy the
      full course of drugs. Seventy-two per cent of total spending on anti-tuberculosis
      drugs was for different kinds of combinations of drugs. Nine per cent was spent
      on plain rifampicin, believed to be sold only to tuberculosis/leprosy patients.
      During the previous month, 5/13 (38%) of pharmacies with no doctors attached had
      sold anti-tuberculosis drugs compared with 27/38 (71%) of pharmacies with doctors
      attached to them (P < 0.05). CONCLUSION: The private sector offers an available
      and acceptable but non-affordable service for many TB patients. A substantial
      amount of anti-TB drugs are being sold in the private pharmacies. There is
      therefore a potential role for pharmacists to play in collaborative efforts
      between the private and public sector in TB control activities.

PMID- 10949325
TI  - Validation of the surveillance system for tuberculosis in Botswana.
AB  - SETTING: Gaborone and Francistown, Botswana, where surveillance data in the 1997
      Electronic Tuberculosis (TB) Register suggest that 39% of pulmonary TB patients
      did not have pre-treatment sputum smear microscopy performed. OBJECTIVE: To
      determine the proportion of patients with reportedly missing pre-treatment sputum
      smear results in 1997 who had smears examined, and to identify stages in the
      system where results were lost. METHODS: Patients with pulmonary TB in 1997 who
      were missing pre-treatment sputum smear results in the Electronic TB Register
      were cross-matched with laboratory records; medical records were reviewed.
      RESULTS: Of 374 patients with pre-treatment sputum smear results missing, 224
      (60%) actually had had a sputum smear examined in the laboratory. The proportion
      of pulmonary TB patients in Gaborone and Francistown who did not have sputum
      examined was therefore 16% instead of 39%. Most missing results (69%) had not
      been transcribed from the laboratory results onto the TB Treatment Card. Patients
      who had a negative smear result or who sought care at a clinic that was different
      from where their diagnostic evaluation had been initiated were more likely to
      have missing results. CONCLUSIONS: The actual performance of the Botswana
      National TB Programme with respect to sputum microscopy examination is much
      better than surveillance indicators suggest. In addition to sputum collection,
      proper recording of results needs reinforcement among health care workers to
      improve routine performance indicators.

PMID- 10949326
TI  - Progress and problems in achieving the United States national target for
      completion of antituberculosis treatment.
AB  - SETTING: The target for antituberculosis treatment in the United States is for
      90% of patients to complete therapy within 12 months. OBJECTIVE: To assess
      progress in achieving the US national target for tuberculosis treatment. DESIGN:
      A comparison of treatment outcome in two cohorts of patients with drug
      susceptible tuberculosis in California-those reported in 1993-1994 (8488
      patients) and 1995-1996 (7823 patients). Risk factors for delay in treatment
      completion (more than 12 months) were assessed. RESULTS: The percentage of cases
      completing treatment within 12 months increased in the 1995-1996 cohort (to
      68.2%), primarily due to concomitant reductions in delays in treatment completion
      (to 11.1%) and defaulting (to 2.4%). Disparities in timely treatment completion
      narrowed over time and in nearly all subpopulations, especially in groups with
      lowest treatment completion in the 1993-1994 cohort. Remaining risk factors for
      delay in treatment completion included AIDS and older ages. A substantial
      percentage of patients died or moved before treatment completion. CONCLUSIONS:
      Despite recent improvements, completion of antituberculosis treatment in
      California has not reached the national target. Reaching this target will require
      further reductions in delays in treatment completion and deaths during treatment,
      and ensuring that patients who move eventually complete treatment.

PMID- 10949327
TI  - Trends in antituberculosis drug resistance in Karonga District, Malawi, 1986
      1998.
AB  - SETTING: Karonga District, Malawi. OBJECTIVES: To examine long term trends in
      initial and acquired resistance to antituberculosis drugs in a rural area of
      Africa. DESIGN: Monitoring of all patients with culture-confirmed tuberculosis
      1986-1998. RESULTS: Initial drug resistance results were available for 1121
      patients. The proportion resistant to any of the first line drugs (streptomycin,
      isoniazid, rifampicin or ethambutol) was 9.6%, and to isoniazid 7.2%. Initial
      resistance to at least isoniazid and rifampicin (multidrug resistance) was seen
      in only six patients. No initial resistance to ethambutol was found. There was no
      significant change in initial drug resistance over time. Overall, 22/120 (18%)
      patients with previous treatment were resistant to at least one drug; only one
      had multidrug resistance. Acquired resistance decreased over the period of the
      study. There were no associations between age, sex or human immunodeficiency
      virus (HIV) status and initial or acquired drug resistance. CONCLUSIONS: Changes
      in acquired resistance may reflect the recent performance of a control programme
      more quickly than those in initial resistance. It is encouraging that acquired
      resistance decreased and levels of multidrug resistance were low despite more
      than a decade of use of rifampicin. The lack of association between HIV and drug
      resistance confirms findings elsewhere in Africa.

PMID- 10949328
TI  - Multidrug-resistant tuberculosis: long-term treatment outcome in the Netherlands.
AB  - SETTING: Tuberculosis units (Beatrixoord, Haren; and Dekkerswald, Groesbeek) in
      the Netherlands. OBJECTIVE: To study the long-term treatment outcome of patients
      with multidrug-resistant tuberculosis (MDR-TB). DESIGN: Descriptive analysis of
      all consecutively admitted patients with MDR-TB between 1 January 1985 and 1
      September 1998, with follow-up until 1 August 1999. RESULTS: Of 44 patients (31
      male) enrolled in the study, 33 were foreign born and none were human
      immunodeficiency virus positive. At diagnosis 38 patients had sputum-smear
      positive pulmonary TB, and converted culture negative after a mean of 6 weeks,
      while six converted to negative later (mean 69 weeks). Most patients had micro
      organisms resistant to several antimycobacterial drugs (mean = median: 5),
      including resistance to isoniazid and rifampin. In-patient treatment lasted a
      mean of 164 days (range 31-481), and patients were treated with six drugs on
      average. Side effects were common. Treatment lasted for a mean of 608 days (range
      268-1626); five patients are still on treatment. Four patients were operated for
      TB, and two others were operated for post-TB sequelae. During the follow-up
      period six patients died, of whom three had active TB; 33 (75%) were considered
      cured. CONCLUSION: Mortality was only 14% after a mean follow-up period of 53
      months. MDR-TB can be successfully treated, but requires much effort from both
      patients and carers, and the costs may be higher than is affordable in resource
      poor countries.

PMID- 10949329
TI  - rpoB mutations as an epidemiologic marker in rifampin-resistant Mycobacterium
      tuberculosis.
AB  - SETTING: Cases of rifampin-resistant Mycobacterium tuberculosis from the prison
      population in Madrid and from the general population in Spain. OBJECTIVE: To
      identify the rpoB mutations associated with resistance to rifampin and to
      investigate rpoB genotyping as an epidemiological marker in rifampin-resistant M.
      tuberculosis. DESIGN: Twenty-nine rifampin-resistant clinical isolates of M.
      tuberculosis, 15 obtained from the prison population in Madrid and 14 from the
      general population in Spain, were characterized by sequence analysis of the 81-bp
      core region of the rpoB gene and IS6110 DNA fingerprinting. RESULTS: All the
      isolates had mutations in rpoB, with those in codon 531 accounting for 41% of the
      total. Twenty-three (79%) isolates were highly resistant to rifampin (minimum
      inhibitory concentration > or = 64 mg/L). Nineteen different IS6110 fingerprints
      were observed: one was shared by seven isolates, one by three, two by two, and 15
      were unique. Two IS6110 clusters could be divided into subclusters on the basis
      of rpoB analysis. Epidemiologic links were identified among patients whose
      isolates had identical IS6110 patterns and rpoB genotypes, but not between those
      with identical IS6110 patterns and different rpoB genotypes. CONCLUSION:
      Characterization of rpoB mutations can provide information about susceptibility
      to rifampin and be a useful epidemiological tool for discrimination of rifampin
      resistant strains of M. tuberculosis with identical IS6110 fingerprints.

PMID- 10949330
TI  - Haptoglobin polymorphism and mortality in patients with tuberculosis.
AB  - SETTING: A rural Zimbabwean hospital and the surrounding community. OBJECTIVES:
      To determine whether a particular haptoglobin phenotype is associated with
      increased susceptibility to clinical pulmonary tuberculosis, and to determine the
      outcome of treatment for pulmonary tuberculosis according to haptoglobin
      phenotype. DESIGN: A case-control study, and a prospective cohort study. RESULTS:
      We studied 98 consecutive patients with sputum-positive pulmonary tuberculosis
      and 98 sex- and age-matched controls. The haptoglobin (Hp) phenotype
      distributions did not differ significantly between the tuberculosis patients and
      controls (P = 0.5). During the 18-month follow-up period after the start of
      tuberculosis treatment, 6/18 (33%) cases with Hp 2-2 phenotype died compared to
      9/47 (19%) with Hp 2-1 and 3/31 (10%) with Hp 1-1. In a logistic regression
      model, the odds of dying were 6.1-fold greater with Hp 2-2 than with Hp 1-1
      (95%CI 1.04-35.1, P = 0.04). CONCLUSION: Our results suggest that there is equal
      susceptibility to clinical pulmonary tuberculosis disease amongst different
      haptoglobin phenotypes. Nonetheless, tuberculosis patients with Hp 2-2 phenotype
      had a higher risk of mortality.

PMID- 10949331
TI  - Survey of mycobacteriology laboratory practices in an urban area with
      hyperendemic pulmonary tuberculosis.
AB  - SETTING: Rio de Janeiro, Brazil, where 10210 cases of tuberculosis (TB) were
      reported in 1997, 86.2% of them with pulmonary TB. OBJECTIVE: To assess
      laboratory resources, practices, biosafety measures and training needs relative
      to the volume of work required for the TB control program and implementation of
      directly observed therapy, short course (DOTS). DESIGN: A cross-sectional survey
      of laboratories that receive funds from the public sector and work with
      mycobacteria, using a structured questionnaire and onsite visits to collect data.
      The main outcome measure of interest was processing > or = 20 specimens per week.
      RESULTS: More than half (56.5%) of the laboratories reported performing < 20
      specimens per week, a level at which it is difficult to maintain proficiency in
      mycobacteriologic techniques. The demand for sputum smear microscopy was not met.
      Working conditions such as shared laboratory and air space, inadequate
      ventilation, accidents with biological specimens, and inadequate disposal of
      biological waste present risks of TB transmission to laboratory workers and other
      staff. CONCLUSION: Training and supervising laboratory workers in good technique
      and biosafety practices and providing the necessary organization, resources and
      working conditions will strengthen TB control and facilitate implementation of
      DOTS. Several simple interventions are proposed.

PMID- 10949332
TI  - Effect of combined therapy of oral anti-tubercular agents on theophylline
      pharmacokinetics.
AB  - To evaluate the effects of combined therapy of anti-tubercular agents with
      theophylline during treatment of concurrent pulmonary tuberculosis and chronic
      obstructive pulmonary disease or asthma, the clearance and half life of
      theophylline was estimated in a control group not treated with anti-tubercular
      agents, a group treated with isoniazid (INH), rifampicin (RMP), ethambutol (EMB)
      and pyrazinamide (PZA), and a group treated with INH, RMP and EMB. Clearances of
      theophylline in the treated groups were significantly lower than in the control
      group, and the half-life of theophylline was longer than in the control. These
      results suggest that patients administered combinations of anti-tubercular agents
      with theophylline require lower doses of theophylline.

PMID- 10949333
TI  - Mammary tuberculosis: rare but still present in the United Kingdom.
AB  - Mammary tuberculosis (TB) is rare and usually affects women from the Indian sub
      continent and Africa. It may be mistaken clinically for carcinoma or pyogenic
      abscess. Tuberculosis (particularly drug-resistant TB) is on the increase in
      areas of the UK with rising numbers of immigrants, some of whom may present with
      breast lesions of uncertain aetiology. Between 1978 and 1997 there were 436 cases
      of TB notified for Indian Sub-continent females aged 15-49 years in Blackburn,
      Hyndburn and Ribble Valley, Lancashire, UK. Ten cases were mammary TB (10/436 =
      2.3%) which was clinically suspected in only three patients preoperatively,
      despite the area having large numbers of immigrants. Mammary TB should be
      included in the differential diagnosis of breast lesions in women from those
      ethnic groups at increased risk of TB. Pus and/or breast tissue samples should be
      subjected to TB culture and histological examination for both diagnosis of TB and
      determination of drug sensitivities.

PMID- 10949334
TI  - Disseminated bacille Calmette-Guerin infection in an infant with a novel deletion
      in the interferon-gamma receptor gene.
AB  - Six weeks after receiving BCG vaccination, a Canadian aboriginal infant presented
      with suspected sepsis, lymphadenopathy and hepatosplenomegaly. Lymph node biopsy
      revealed macrophages filled with acid-fast bacilli. Mycobacterium bovis was
      cultured from tissue specimens and there was evidence of concomitant
      cytomegalovirus disease. The infant died of disseminated BCG infection. A novel
      deletion at nucleotide 165 in the interferon-gamma receptor (IFN-gammaR1) was
      identified. The incidence of this mutation in the aboriginal population and the
      impact on the heterozygous state are unknown.

PMID- 10949335
TI  - Repair of large, anterior palatal fistulas using thin tongue flaps: long-term
      follow-up of 10 patients.
AB  - Anteriorly based, thin tongue flaps were used in 10 patients to close large,
      anterior palatal fistulas. All 10 flaps (100%) survived, and complete closure was
      obtained in all patients, with the exception of a recurrent fistula that occurred
      in 1 patient during maxillary expansion (10%). Another patient (10%) demonstrated
      postoperative bleeding that required formal hemostasis under general anesthesia.
      No other complications were encountered. The results of this series indicate that
      the tongue flap is a safe technique for closure of large, anterior palatal
      fistulas. This thin, long flap is also reliable for orthodontic maxillary
      expansion.

PMID- 10949336
TI  - Immediate coverage of exposed, denuded cranial bone with split-thickness skin
      grafts.
AB  - Avulsion injuries of the scalp are challenging to treat. If the periosteum is not
      intact and the status of local tissues does not allow local flap transposition,
      coverage of the exposed, denuded skull becomes a problem. Most authors have
      obtained a bed of granulation tissue at the site of exposed bone before skin
      grafting, which requires a prolonged waiting period. In 5 consecutive patients,
      the authors obtained coverage in a single operation by removing the outer table
      of the skull with a high-speed burr, followed by immediate application of a skin
      graft over the bleeding, cancellous bone. This resulted in stable coverage and
      shortened the hospital stay significantly. They describe their technique and
      compare it with others.

PMID- 10949337
TI  - Long-term results of tendon transfers for radial nerve palsy in patients with
      limited rehabilitation.
AB  - The authors reviewed the long-term functional results of 22 patients who
      underwent tendon transfer for isolated radial nerve palsy. The average number of
      postoperative visits was eight (range of postoperative visits, 3-16), and the
      mean follow-up was 6.3 years. All but 1 patient had improved function after the
      tendon transfers, and could cope with the activities of daily living. Radial
      deviation of the wrist at rest was present in 10 of the 15 patients with flexor
      carpi ulnaris transfer and in 2 of 7 patients with flexor carpi radialis
      transfer, with a mean of 14.5 deg (range of radial deviation, 5-30 deg). Although
      a global decrease in wrist power and power grip was noted, 13 of 17 previously
      employed patients were able to work after transfer; however, only 1 of 7 heavy
      manual laborers was able to return to his previous employment. Despite the poor
      clinic attendance, the overall functional results compared favorably with other
      published series. It appears that tendon transfer for radial nerve palsy is a
      viable option, even in patients with limited rehabilitation.

PMID- 10949338
TI  - Correlation of electrodiagnostic findings with subjective symptoms in carpal
      tunnel syndrome.
AB  - The records of 138 patients (222 hands) who had been evaluated by preoperative
      nerve conduction study (NCS) and consecutive self-administered questionnaires
      were analyzed to determine diagnostic relations in carpal tunnel syndrome. Hands
      were categorized into six grades (extreme, severe, moderate, mild, minimal, and
      negative) according to the three modalities: the NCS data of the median sensory
      nerve, Symptom Severity Scale score, and Functional Status Scale score. The
      authors evaluated the correlation, independence, homogeneity, and association
      among parameters, and found the following: (1) the NCS data correlated more
      significantly (p < 0.05) and was associated more linearly with Symptom Severity
      Scale score than the Functional Status Scale score; (2) the choice of modality
      exerted an influence on grading severities, thus grades varied according to the
      modalities; and (3) the distribution of patients was not homogenous; there were
      more extremes in NCS, and more severe scores on the Symptom Severity Scale.
      Patients rated as one homogeneous severity by NCS data may be interpreted into
      different severities (from negative to extreme) by self-administered
      questionnaires and vice versa.

PMID- 10949339
TI  - The distally based superficial sural flap: our experience in reconstructing the
      lower leg and foot.
AB  - The treatment of soft-tissue defects of the lower third of the leg and foot is
      often an awkward problem to tackle because of the frequent involvement of muscle,
      tendon, and bone, which is caused by the thinness and poor circulation of the
      skin covering them and by the small quantity of local tissue available for
      reconstruction. The authors present their experience with the use of sural flaps
      for the treatment of small- and medium-size defects of the distal region of the
      lower limb. The flap used was a distally based fasciocutaneous flap raised in the
      posterior region of the lower two thirds of the leg. Vascularization was ensured
      by the superficial sural artery, which accompanies the sural nerve together with
      the short saphenous vein. The authors treated 18 patients (12 men and 6 women)
      from May 1997 to August 1999 at the Division of Plastic Surgery, University of
      Turin, Italy. Superficial necrosis without involvement of the deep fascia (which
      was grafted 1 month later) occurred in 1 patient of the 18 treated. In another 2
      patients, defects were found in the flap margins, but no additional surgical
      revision was necessary, and recovery occurred by secondary intention. In every
      patient the sural flaps provided good coverage of the defects, both from a
      functional and an aesthetic point of view. The major advantages of this flap are
      its easy and quick dissection. Because the major arterial axis is not sacrificed,
      this flap can be used in a traumatic leg with damaged major arteries.

PMID- 10949340
TI  - Rotation ligamentoplasty for the correction of epicanthus inversus.
AB  - Epicanthus, with its various types, is characterized by an arching fold at the
      sides of the nose, with a concavity directed laterally. Epicanthus inversus, one
      of these types, which occurs with varying frequency in all races, is most common
      among Asians. In epicanthus inversus, the medial canthus is displaced laterally
      and the medial canthal depression is shallow or absent. The lower puncta is
      displaced laterally as well. Correction of epicanthus is easy with Z-plasties or
      with the four-flap technique of Mustarde. However, inverted epicanthus cannot be
      repaired using these techniques, as proved by others. The authors suggest
      rotating the medial canthal ligament during transnasal wiring to support the
      eversion of the laterally displaced medial lower lid, lower puncta, and
      surrounding skin. Eight patients with epicanthus inversus were operated and
      followed for at least 15 months. The results were satisfactory according to a
      graded scale.

PMID- 10949341
TI  - The limitation of primary excision of cicatricial alopecia: a report of 63
      patients.
AB  - This 11-year retrospective study (1985-1996) of 63 patients demonstrates that
      cicatricial alopecia is almost always distressing for the patient and is
      considered as a social handicap, which makes repair a necessity. Two major
      therapeutic methods for remedying this condition were used in the study: suture
      excision and tissue expansion. The optimal use and limitations of each method are
      defined on the basis of treatment quality, as evaluated by the patient and the
      surgeon. Suture excision often ends with disappointing results for the surgeon as
      well as the patient and seems limited to alopecias no greater than 10 mm in
      width. Tissue expansion is considered generally satisfactory, but has the problem
      of scar enlargement, which reduces the quality of the result.

PMID- 10949342
TI  - Cartilage shaping using the Er:YAG laser: preliminary report.
AB  - Cartilage grafts have been widely used for reconstruction of congenital or
      acquired deformities. Reshaping and preserving the new shape of the cartilage
      grafts have been a problem. In this in vitro experimental study the authors
      studied the effect of the Er:YAG laser on cartilage reshaping in comparison with
      scalpel stripping and suture holding. The study consisted four groups (n = 9):
      group I, untouched cartilage; group II, the short edges of the cartilage were
      sutured to each other; group III, cartilage was incised using a scalpel; and
      group IV, Er:YAG laser stripping was applied to the cartilage. Changes in the
      shape of cartilage were evaluated at 15 minutes, and days 1, 4, and 10. The
      majority of cartilage in the scalpel-stripped group returned to the initial shape
      by day 10, whereas the laser-stripped cartilage showed progressive warping day by
      day, and almost all cartilage formed a circle by day 10. The Er:YAG laser
      enhanced cartilage warping by a mechanical effect of stripping and a thermal
      effect of laser radiation resulting in ultrastructural changes.

PMID- 10949343
TI  - The effect of pedicle artery vasospasm on microhemodynamics in anatomically
      perfused and extended skin flap tissue.
AB  - The aim of this study was to evaluate quantitatively the influence of pedicle
      artery vasospasm on the microcirculation in skin flaps, particularly in the
      jeopardized extended portions. For this purpose, the hamster island skin flap
      model was used, which allowed for simultaneous assessment of hemodynamics in both
      the pedicle artery and the microvasculature of the flap by intravital microscopy.
      Vasospasm was induced by applying a V3 microvascular clamp for 30 seconds.
      Clamping resulted in a severe vasospasm, with the artery exhibiting a diameter of
      7% +/- 2% (mean +/- standard error) of its original diameter (n = 10; p < 0.01),
      and with a reduction of total blood flow to the flap of 11% +/- 2% (p < 0.01).
      Diameter and blood flow recovered gradually to baseline levels after 25 and 15
      minutes respectively. During recovery from severe pedicle artery vasospasm
      (moderate to mild vasospasm), the arterioles in the anatomically perfused flap
      tissue (n = 38) showed reactive vasodilation (p < 0.01), which was absent in the
      extended tissue (n = 49; p < 0.01 vs. anatomic). At a pedicle artery vasospasm of
      50% of the original diameter, blood flow was restored to normal levels in the
      anatomically perfused arterioles, but remained below baseline in the extended
      part (partly p < 0.05 vs. baseline and anatomic). The findings suggest that the
      development of ischemic necrosis in extended flap portions may be promoted by
      prolonged, moderate vasospasm, which is well tolerated in the anatomically
      perfused tissue because of its high capacity for implementing compensatory local
      regulatory mechanisms.

PMID- 10949344
TI  - Both dermal matrix and epidermis contribute to an inhibition of wound
      contraction.
AB  - Contracture is a major detriment to functional recovery from large wounds. To
      determine the relative value of dermal replacement and epidermal coverage in
      inhibiting wound contraction, five full-thickness wounds (all 5 x 5 cm2) were
      placed on the back of 8 swine and treated in the following manner: (1) open
      wound, (2) porcine acellular dermis (analogous to AlloDerm for human use), (3)
      porcine acellular dermis with epidermal autograft placed 7 days postwounding, (4)
      porcine acellular dermis with immediate epidermal autograft, and (5) conventional
      thickness autograft. Scar dimensions and punch biopsies were taken at days 14 and
      30 postwounding. The planimetry results demonstrated that wound contraction was
      significantly greater with the open wounds (group 1) than all other wounds with a
      dermal substitute. Furthermore, wounds with initial epidermal coverage had
      significantly less contraction than unepithelialized wounds (14.8 +/- 1.1 cm2 at
      day 14 in wound group 2 vs. 20.4 +/- 0.6 cm2 in wound group 4; p < 0.05). Biopsy
      results revealed that wounds with initial epithelial coverage had the least
      amount of inflammation. These findings suggest that both dermal matrix and
      epidermal coverage contribute to an inhibition of wound contraction and that
      prompt epithelial coverage appears to impede contraction by reducing
      inflammation.

PMID- 10949345
TI  - Hyperbaric oxygen therapy in adriamycin extravasation: an experimental animal
      study.
AB  - Adriamycin extravasation is a serious problem that can lead to severe local
      necrosis and damage to underlying nerves, tendon, and muscle. There are some
      experimental studies in which conflicting results were reported about the
      beneficial effects of hyperbaric oxygen (HBO) in adriamycin-induced skin lesions.
      In this study the effect of HBO on the healing of adriamycin-induced wounds was
      investigated in the Wistar-Albino rat model. Ninety-five rats underwent injection
      of a 0.7-ml adriamycin solution (2 mg per milliliter) subcutaneously on the right
      upper hind legs. The HBO group (n = 43) received HBO treatment (at 2.5 ATA for 80
      minutes) twice a day for 28 days. The control group (n = 42) did not receive any
      therapy. Lesion size was measured for 4 weeks. There was no significant
      difference in lesion size between the groups on days 7 (p = 0.1364) and 14 (p =
      0.1123), but the lesion size was significantly smaller in the HBO group than in
      the control group on days 21 (p = 0.0251) and 28 (p = 0.0001). Of 36 animals with
      lesions in the HBO group, complete wound healing occurred in 16 animals by day
      40. However, there was no complete wound healing in any of the 36 animals with
      lesions in the control group. The beneficial effect of HBO in adriamycin-induced
      skin lesions was observed in this experimental study.

PMID- 10949346
TI  - Are triglyceride breast implants really biocompatible?
AB  - A case of augmentation mammaplasty with triglyceride implants is presented.
      Histological examination of the capsules 3 years postimplantation showed
      retained, irregular, refractile yellow-brown fragments embedded in granulomatous
      tissue.

PMID- 10949347
TI  - Reconstruction of hip abduction using free muscle transplantation: a case report
      and description of the technique.
AB  - The authors describe a free-functioning latissimus dorsi muscle transplantation
      for reconstruction of hip abduction. A radical "buttockectomy" was performed on a
      62-year-old patient with recurrent soft-tissue sarcoma. The patient received a
      muscle transplantation immediately after resection of the tumor. Until recovery
      of the muscle, a complete absence of hip abductors resulted in a marked lurch in
      the patient's gait, requiring him to use walking aids. Reinnervation of the
      muscle was confirmed via electromyography 6 months after surgery. Hip abduction
      was restored along with muscle recovery, and walking support was no longer
      required. Although the strength of the muscle was not sufficiently powerful to
      overcome gravity fully, the latissimus dorsi muscle improved markedly the
      performance of an otherwise unstable hip. This patient demonstrates that
      microsurgical reconstruction is of great value in enhancing the functional
      outcome of a salvaged limb after tumor surgery.

PMID- 10949348
TI  - Total tongue reconstruction with free functional gracilis muscle transplantation:
      a technical note and review of the literature.
AB  - The tongue is one of the most difficult structures of the body to reconstruct if
      more than 85% to 90% of it has been resected. A functional neotongue requires
      both soft-tissue bulk and restoration of muscle function. The innervated gracilis
      muscle flap folded on itself was used to reconstruct a total glossectomy defect.
      The genioglossus muscle, which makes the greatest contribution to swallowing, and
      the mylohyoid muscle, which elevates the larynx to prevent aspiration, were
      simulated with the design and placement of the gracilis muscle. The muscle was
      placed and secured longitudinally from the remnant of the tongue base and pharynx
      to the mandible, and then folded on itself and attached to the hyoid bone. The
      obturator nerve to the gracilis was coapted with the hypoglossal nerve. The
      patient was able to resume oral feeding without aspiration. Electromyographic
      results demonstrated reinnervation of the flap with active elevation of the mouth
      base. The patient died 1 year postoperatively because of recurrence of her
      disease. This type of design and placement of gracilis muscle transplantation is
      recommended.

PMID- 10949349
TI  - New multilobe "accordion" flaps for three-dimensional reconstruction of wide,
      full-thickness defects in the oral floor.
AB  - When reconstructing a wide, full-thickness intraoral defect, the following
      principles are necessary for active food transport and improved swallowing and
      speech. First, the flap should touch the palate and obliterate the oral cavity.
      Second, jaw or flap excursion should not be hindered by tethering of the flap in
      the neck. And third, all surfaces of the tongue and oral floor, and the dead
      space of the floor should be reconstructed. To accomplish these goals, two new
      designs, similar to an accordion, using an anterolateral thigh flap and a deep
      inferior epigastric perforator flap have been developed. The outlines of
      multilobe flaps create an accordion-type structure of the tongue and oral floor
      complex. The advantages of the new designs using anterior thigh or deep inferior
      epigastric perforator flaps are follows: First, three-dimensional intraoral
      reconstitution allows maximal movement postoperatively of the reconstructed
      tongue. Second, the donor sites are so far from the tongue that simultaneous flap
      elevation is possible for tumor resectioning. Third, even in obese patients,
      totally or partially thin flaps are available. And fourth, in most patients the
      donor defects can be closed directly.

PMID- 10949350
TI  - The compound sternal flap for laryngeal reconstruction.
AB  - The authors present the successful transfer of a compound flap based on the
      sternocleidomastoid muscle in a patient who had undergone radiation therapy and a
      near-total laryngectomy. The surgical procedure, a one-stage reconstruction with
      a regional rotational flap, utilized a segment of the sternal periosteum and
      underlying anterior cortex attached to the sternal belly of the
      sternocleidomastoid muscle. The rigid wall provided by the flap over the
      temporary laryngeal endoprosthetic stent was an adequate replacement for the
      subtotally resected larynx, obviated the need for postoperative tracheostomy and
      nasogastric feeding, prevented collapse or stenosis of the airway, spared the
      voice, and provided an excellent functional result. This reliable flap presents a
      regional alternative to other local tissue transfers, such as epiglottic
      laryngoplasty, and more complicated microsurgical reconstructions.

PMID- 10949351
TI  - When is surgical treatment not appropriate for morphea?
AB  - Morphea is an inflammatory cutaneous disease that can be mistaken for a soft
      tissue neoplasm. The authors report two cases of morphea that were resected
      surgically before the histological diagnosis of morphea was rendered. One of the
      patients had a recurrence of morphea around her large surgical scar. They present
      these cases to alert surgeons to the pitfall of inappropriate surgical treatment
      of an inflammatory condition.

PMID- 10949352
TI  - Reconstruction of a tibial defect with microvascular transfer of a previously
      fractured fibula.
AB  - A 43-year-old man sustained severe injuries to his lower limbs with extensive
      soft-tissue damage and bilateral tibial-fibular fractures. Acutely, the patient
      underwent external fixation and a free latissimus dorsi flap for soft-tissue
      coverage of the left leg. However, the tibia had a nonviable butterfly fragment
      that left a 7-cm defect after debridement. Subsequently, the contralateral
      fractured fibula was used as a bridging vascularized graft for this tibial
      defect. The transfer of a fibula containing the zone of injury from a previous
      high-energy fracture has not been reported. This case demonstrates the successful
      microvascular transfer of a previously fractured fibula for the repair of a
      contralateral tibial bony defect.

PMID- 10949353
TI  - Clinical and scientific considerations in leech therapy for the management of
      acute venous congestion: an updated review.
AB  - Any surgical intervention that involves the manipulation of veins, large or
      small, carries the risk of acute venous congestion. Venous congestion is the
      product of an imbalance between arterial inflow and venous outflow, and results
      in the stasis of blood in the tissues that are normally drained by the affected
      veins. The resultant lack of tissue perfusion causes hypoxia, acidosis, and
      arterial thrombi formation, which can potentially progress to tissue necrosis and
      wet gangrene. In the past several decades, the use of leeches (Hirudo
      medicinalis) has been rediscovered as an effective method of relieving acute
      venous congestion. This updated review of leech therapy focuses on the use of
      medicinal leeches in a variety of clinical conditions characterized by acute
      venous congestion, and points out the experimental use of leeches in other
      pathological entities. A discussion of the recent scientific findings that
      explain the possible mechanisms of action of leech therapy is also provided.

PMID- 10949354
TI  - Rhapsody in Greek.

PMID- 10949355
TI  - Re: What's the alternative?

PMID- 10949356
TI  - Re: Transsacral usage of an island TRAM flap for sacral defects.

PMID- 10949357
TI  - Urethral fistula as the cause of circumcision phobia.

PMID- 10949358
TI  - A new tool to eliminate hyperpigmentation in liposuction scars.

PMID- 10949359
TI  - Pediatric plastic surgery in a day hospital: use of propofol and a laryngeal
      mask.

PMID- 10949360
TI  - A giant recurrent pyogenic granuloma of the thumb.

PMID- 10949361
TI  - Re: Soft tissue reconstruction of sole and heel defects with free tissue
      transfers.

PMID- 10949362
TI  - Microphthalmia with linear skin deficiency syndrome accompanied by cleft lip and
      palate.

PMID- 10949363
TI  - Simultaneous use of a tissue expander and skin graft in scalp reconstruction.

PMID- 10949364
TI  - Pacinian corpuscle hyperplasia coexisting with Dupuytren's contracture.

PMID- 10949365
TI  - Palliative amputation for a peculiar case of malignant melanoma of the lower
      limbs.

PMID- 10949366
TI  - Idiopathic calcinosis of the scrotum.

PMID- 10949367
TI  - The effects of oxidized, regenerated cellulose on diced cartilage xenografts: an
      experimental study.

PMID- 10949368
TI  - Re: Treatment of painful neuromas: a case report.

PMID- 10949369
TI  - Isolation and characterization of a dehydrin gene from white spruce induced upon
      wounding, drought and cold stresses.
AB  - A cDNA clone encoding a dehydrin gene was isolated from a cDNA library prepared
      from white spruce (Picea glauca) needle mRNAs. The cDNA, designated PgDhn1, is
      1159 nucleotides long and has an open reading frame of 735 bp with a deduced
      amino acid sequence of 245 residues. The PgDhn1 amino acid sequence is highly
      hydrophilic and possesses four conserved repeats of the characterized lysine-rich
      K-segment (EKKGIMD-KIKEKLPG), and an 8-serine residue stretch prior to the first
      lysine-rich repeat that is common to many dehydrins. The DEYGNP conserved motif
      is, however, absent in the PgDhn1 sequence. In unstressed plants, the highest
      level of transcripts was detected in stem tissue and not fully expanded
      vegetative buds. PgDhn1 expression was also clearly detected in reproductive
      buds, at various stages of development. The mRNAs corresponding to PgDhn1 cDNA
      were induced upon wounding and by jasmonic acid (JA) and methyl jasmonate (MeJa)
      treatments. Upon drought stress, increased transcript accumulation was observed
      in needle tissue reaching a maximum level 48 h after treatment. Treatments of
      seedlings with abscisic acid or ethephon also resulted in high levels of
      transcript accumulation in needle tissue. Finally, cold induction of PgDhn1
      transcripts was also detected as early as 8 h after treatment.

PMID- 10949370
TI  - Anaerobiosis-specific interaction of tobacco nuclear factors with cis-regulatory
      sequences in the maize GapC4 promoter.
AB  - The promoter of the maize glyceraldehyde-3-phosphate dehydrogenase 4 gene (GapC4)
      confers strong, specific and ubiquitous anaerobic reporter gene expression in
      tobacco. To identify factors required for heterologous anaerobic gene expression,
      19 progressive 5' and 3' promoter deletions were linked to a chimeric GapC4 TATA
      box-beta-glucuronidase (GUS) reporter gene construct and transformed into
      tobacco. In all transgenic lines aerobic expression values were in the range
      obtained for negative controls while histochemical GUS assays reveal some weak
      expression in roots only. Anaerobic induction of about 100-fold to more than 1000
      fold above unspecific background is mediated by a region of about 190 bp of the
      GapC4 promoter. Anaerobic reporter gene induction strongly decreases upon
      deletion of a 20 bp fragment from -286 to -266 relative to the transcription
      start point. This fragment harbours putative cis-acting sequences.
      Electrophoretic mobility shift assays with a 50 bp fragment harbouring these cis
      sequences reveal a high-mobility complex that is formed with nuclear extracts
      from aerobic and anaerobic leaf tissue while an additional low-mobility complex
      is anaerobiosis-specific. The formation of the high-mobility complex requires the
      sequence GTGGGCCCG. The 50 bp fragment alone confers weak and orientation
      dependent anaerobic induction to a GapC4 TATA box-beta-glucuronidase (GUS)
      reporter gene.

PMID- 10949371
TI  - Electron transport controls transcription of the thioredoxin gene (trxA) in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - The trxA gene encoding one of the different thioredoxins of the facultative
      heterotrophic cyanobacterium Synechocystis sp. PCC 6803 is transcribed as a
      single mRNA of 450 nucleotides. Transcript accumulation is similar in all
      standard growth conditions but strongly decreases after transferring cell
      cultures from light to darkness. In steady-state conditions, trxA transcription
      is reduced at high (150-500 microE m(-2) s(-1)) compared with moderate (10-50
      microE m(-2) s(-1)) light intensities. The stability of the trxA transcript was
      similar at different light intensities, and also in darkness. Photosynthetic
      electron transport inhibitors, as well as glucose starvation in a mutant strain
      lacking photosystem II, promote a strong decline in the level of trxA transcript.
      Primer extension analysis suggests that trxA is transcribed from two proximal
      promoters containing a -10 TATA box similar to the Escherichia coli consensus
      promoters. Unlike the trxA mRNA, the amount of thioredoxin protein was not
      reduced in the dark, neither at high light intensities, indicating that
      thioredoxin protein is very stable. Our results indicate that the thioredoxin
      encoded by the trxA gene is likely to be primarily regulated at the
      transcriptional level, rather than at the protein level, by the electron
      transport generated photosynthetically or from glucose metabolism.

PMID- 10949372
TI  - Characterization of site-directed mutants in manganese-stabilizing protein (MSP)
      of Synechocystis sp. PCC6803 unable to grow photoautotrophically in the absence
      of cytochrome c-550.
AB  - To investigate the interaction between the manganese-stabilizing protein (MSP)
      and cytochrome c-550 (cyt. c-550) of the photosystem II (PSII) complex in the
      cyanobacterium Synechocystis sp. PCC6803, three site-directed amino acid
      substitution mutants in MSP (MSP-D159N, MSP-R163L, MSP-D 159N/R 163L) were
      created by single and double amino acid substitution mutagenesis. The modified
      psbO genes encoding the mutants forms of MSP were used to transform a single
      deletion mutant deltapsO strain lacking MSP as well as a double-deletion strain
      deltapsbO:deltapsbV lacking both MSP and cyt. c-550. The mutant forms of MSP were
      expressed in each case and all permitted autotrophic growth in strains expressing
      cyt. c-550. However, when the MSP mutations were introduced into a strain which
      lacks cyt. c-550 (deltapsbV), the two single amino acid substitution mutants
      (deltapsbV:MSP-D159N and deltapsbV:MSP-R 163L) failed to grow
      photoautotrophically. These strains exhibited coupled O2-evolving activity of 68
      77% compared to the wild-type control using CO2 as an electron acceptor and
      maximal uncoupled O2-evolution rates of 42-57% using 2,6-dichloro-p-benzoquinone
      (DCBQ) as an artificial electron acceptor. Interestingly, when the two amino acid
      substitutions were together in the absence of cyt. c-550 (deltapsbV:MSP
      D159N/R163L), the mutant grew photoautotrophically and the oxygen-evolving
      activities were higher than in the single mutants. This indicates that the MSP
      D159N mutant suppresses the non-autotrophic phenotype of MSP-R163L (or vice
      versa) in the absence of cyt. c-550. The possibilities of a direct (ionic) or
      indirect interaction between D159 and R163 of MSP are discussed.

PMID- 10949374
TI  - Constitutive expression of the defense-related Rir1b gene in transgenic rice
      plants confers enhanced resistance to the rice blast fungus Magnaporthe grisea.
AB  - The Rirlb gene of rice (Oryza sativa) is one of a set of putative defense genes
      whose transcripts accumulate upon inoculation of rice with the non-host pathogen
      Pseudomonas syringae pv. syringae. It belongs to a family of genes encoding small
      extracellular proteins so far only identified in cereals. To assess the function
      of the Rirlb gene in rice blast resistance, it was placed under the control of
      the CaMV 35S promoter and transferred into rice plants of the japonica variety
      Taipei 309 by biolistic transformation of immature embryos. Two out of 12
      hygromycin-resistant regenerated plants (OE1 and OE3) were fertile. DNA gel blot
      analysis suggested that these two T0 plants were independent transformants, each
      of which had stably incorporated one complete copy of the transgene into the
      genome. In addition, the OE1 plant appeared also a contain a rearranged copy or
      incomplete copy. T1 plants homozygous for the transgene were identified by DNA
      gel blot analysis of individual T2 progeny and further propagated. Expression
      analysis of the transgene showed that the transgene was active both in T1 plants
      and homozygous decendants. Challenge inoculation of homozygous transgenic plants
      with Magnaporthe grisea, the causal agent of rice blast disease, revealed that
      both independent transgenic lines were more resistant than the untransformed wild
      type, suggesting that over-expression of the Rirlb gene confers partial
      resistance against this important pathogen.

PMID- 10949373
TI  - Alternative transcript initiation and novel post-transcriptional processing of a
      leucine-rich repeat receptor-like protein kinase gene that responds to short-day
      photoperiodic floral induction in morning glory (Ipomoea nil).
AB  - A gene (inrpk1) encoding a putative receptor-like protein kinase was isolated
      from the Japanese morning glory, Ipo-moea (Pharbitis) nil Roth. cv. Violet. The
      receptor-like portion of the largest derived polypeptide contains 26 direct
      leucine-rich repeats (LRRs) in a single block, and the catalytic portion has all
      the conserved amino acid residues characteristic of Ser/Thr protein kinases. RNA
      blot analysis detected multiple transcripts in cotyledons. The largest (4.4 kb)
      transcript encodes the predicted full length polypeptide (INRPK1), whereas a 1.6
      kb transcript apparently originates from a secondary transcription initiation
      site within the gene and potentially encodes a protein kinase identical to INRPK1
      but lacking most of the LRRs. Two transcripts (ca. 2.7 and 2.6 kb) are created by
      alternative 3'-splicing of a large (ca. 1.4-1.5 kb) cryptic intron in the LRR
      region, creating one transcript (2.6 kb) potentially encoding a small, secretable
      polypeptide. The larger transcript encoding a polypeptide identical to INRPK1,
      but lacking 21 LRRs, predominates in vegetative roots. Competitive PCR indicates
      that inrpk1 mRNA increases 20-fold in cotyledons in response to a previously
      given single floral-inducing short-day (SD). No differences of this magnitude
      were detected in any other organs examined from plants similarly treated. This
      pattern of expression and differential processing suggests a role for inrpk1 in
      some aspect of SD photoperiodic-induced flowering in morning glory.

PMID- 10949375
TI  - High-efficiency silencing of a beta-glucuronidase gene in rice is correlated with
      repetitive transgene structure but is independent of DNA methylation.
AB  - Two transgenic callus lines of rice, stably expressing a beta-glucuronidase (GUS)
      gene, were supertransformed with a set of constructs designed to silence the
      resident GUS gene. An inverted-repeat (i/r) GUS construct, designed to produce
      mRNA with self-complementarity, was much more effective than simple sense and
      antisense constructs at inducing silencing. Supertransforming rice calluses with
      a direct-repeat (d/r) construct, although not as effective as those with the i/r
      construct, was also substantially more effective in silencing the resident GUS
      gene than the simple sense and antisense constructs. DNA hybridisation analyses
      revealed that every callus line supertransformed with either simple sense or
      antisense constructs, and subsequently showing GUS silencing, had the silence
      inducing transgenes integrated into the plant genome in inverted-repeat
      configurations. The silenced lines containing i/r and d/r constructs did not
      necessarily have inverted-repeat T-DNA insertions. There was significant
      methylation of the GUS sequences in most of the silenced lines but not in the
      unsilenced lines. However, demethylation treatment of silenced lines with 5
      azacytidine did not reverse the post-transcriptional gene silencing (PTGS) of
      GUS. Whereas the levels of RNA specific to the resident GUS gene were uniformly
      low in the silenced lines, RNA specific to the inducer transgenes accumulated to
      a substantial level, and the majority of the i/r RNA was unpolyadenylated.
      Altogether, these results suggest that both sense- and antisense-mediated gene
      suppression share a similar molecular basis, that unpolyadenylated RNA plays an
      important role in PTGS, and that methylation is not essential for PTGS.

PMID- 10949376
TI  - The families of papain- and legumain-like cysteine proteinases from embryonic
      axes and cotyledons of Vicia seeds: developmental patterns, intracellular
      localization and functions in globulin proteolysis.
AB  - Families of papain- and legumain-like cysteine proteinases (CPR) were found in
      Vicia seeds. cDNAs and antibodies were used to follow organ specificity and the
      developmental course of CPR-specific mRNAs and polypeptides. Four papain-like
      cysteine proteinases (CPR1, CPR2, proteinase A and CPR4) from vetch seeds (Vicia
      sativa L.) were analysed. CPR2 and its mRNA were already found in dry embryonic
      axes. CPR1 was only detected there during early germination. Both CPR1 and CPR2
      strongly increased later during germination. In cotyledons, both CPR1 and CPR2
      were only observed one to two days later than in the axis. Proteinase A was not
      found in axes. In cotyledons it could only be detected several days after seeds
      had germinated. CPR4 mRNA and polypeptide were already present in embryonic axes
      and cotyledons during seed maturation and decreased in both organs during
      germination. Purified CPR1, CPR2 and proteinase A exhibited partially different
      patterns of globulin degradation products in vitro. Although the cDNA-deduced
      amino acid sequence of the precursor of proteinase A has an N-terminal signal
      peptide, the enzyme was not found in vacuoles whereas the other papain-like CPRs
      showed vacuolar localization. Four different legumain-like cysteine proteinases
      (VsPB2, proteinase B, VnPB1 and VnPB2) of Vicia species were analysed. Proteinase
      B and VnPB1 mRNAs were detected in cotyledons and seedling organs after seeds had
      germinated. Proteinase B degraded globulins isolated from mature vetch seeds in
      vitro. VsPB2 and proteinase B are localized to protein bodies of maturing seeds
      and seedlings, respectively, of V. sativa. Like VsPB2 from V sativa, also VnPB2
      of V. narbonensis corresponds to vacuolar processing enzymes (betaVPE). Based on
      these results different functions in molecular maturation and mobilization of
      storage proteins could be attributed to the various members of the CPR families.

PMID- 10949377
TI  - Enhanced tolerance to salt stress in transgenic rice that overexpresses
      chloroplast glutamine synthetase.
AB  - The potential role of photorespiration in the protection against salt stress was
      examined with transgenic rice plants. Oryza sativa L. cv. Kinuhikari was
      transformed with a chloroplastic glutamine synthetase (GS2) gene from rice. Each
      transgenic rice plant line showed a different accumulation level of GS2. A
      transgenic plant line, G39-2, which accumulated about 1.5-fold more GS2 than the
      control plant, had an increased photorespiration capacity. In another line, G241
      12, GS2 was almost lost and photorespiration activity could not be detected.
      Fluorescence quenching analysis revealed that photorespiration could prevent the
      over-reduction of electron transport systems. When exposed to 150 mM NaCl for 2
      weeks, the control rice plants completely lost photosystem II activity, but G39-2
      plants retained more than 90% activity after the 2-week treatment, whereas G241
      12 plants lost these activities within one week. In the presence of isonicotinic
      acid hydrazide, an inhibitor of photorespiration, G39-2 showed the same salt
      tolerance as the control plants. The intracellular contents of NH4+ and Na+ in
      the stressed plants correlated well with the levels of GS2. Thus, the enhancement
      of photorespiration conferred resistance to salt in rice plants. Preliminary
      results suggest chilling tolerance in the transformant.

PMID- 10949379
TI  - Preventing breast cancer.

PMID- 10949378
TI  - Phytobilin biosynthesis: the Synechocystis sp. PCC 6803 heme oxygenase-encoding
      ho1 gene complements a phytochrome-deficient Arabidopsis thalianna hy1 mutant.
AB  - The phytobilin chromophores of phycobiliproteins and phytochromes are
      biosynthesized from heme in a pathway that begins with the opening of the
      tetrapyrrole macrocycle of protoheme to form biliverdin IXalpha, in a reaction
      catalyzed by heme oxygenase. An Arabidopsis thaliana hy1 mutant was previously
      shown to be deficient in phytochrome responses, and these responses were regained
      when the plants were administered biliverdin IXalpha. A heme oxygenase-encoding
      gene, ho1, was recently cloned from the cyanobacterium Synechocystis sp. PCC
      6803. When ho1 was expressed in Escherichia coli, the cells produced active
      ferredoxin-dependent soluble heme oxygenase. The open reading frame of ho1 was
      fused in frame with a chloroplast transit peptide-encoding sequence from the oli
      gene of Antirrhinum majus. This construct was placed in a binary plasmid
      vectorcontaining a kanamycin resistance marker and a cauliflower mosaic virus 35S
      promoter to control expression of the chimeric oli-ho1 gene and used to transform
      A. thaliana hy1 plants. Two independent transformed lines were obtained that had
      the phenotype of the parental Landsberg erecta line and expressed the chimeric
      gene, as indicated by detection of its mRNA by reverse transcriptase-polymerase
      chain reaction. The results indicate that Synechocystis sp. PCC 6803 heme
      oxygenase encoded by ho1 can substitute for the defective HY1 gene product and
      that the only required enzyme activity of the HY1 gene product is heme oxygenase.

PMID- 10949380
TI  - Lymphadenectomy in ovarian cancer.
AB  - Current guidelines for the surgical staging of ovarian cancer include the removal
      of retroperitoneal lymph nodes (pelvic and aortic). In most centres this is
      achieved by means of laparotomy, but advanced laparoscopic techniques have also
      been performed and still further prospective controlled studies with long-term
      follow-up are necessary to validate the efficacy. Lymph node sampling, short of
      complete dissection, should be avoided because it may be insufficient to detect
      metastasis. In any case, laparoscopic lymphadenectomy as well as open surgery,
      should be in the hands of properly trained subspecialists in gynaecologic
      oncology. Of 97 patients with ovarian carcinoma studied in our hospital, 68% were
      treated by means of complete staging laparotomy (FIGO). Lymphadenectomy was
      spared in 14 cases with stage I tumours (mainly serous) without changes in
      overall survival. In 15% metastases in pelvic lymph nodes were present. In the
      same proportion aortic lymph nodes were positive. In 5.5%, aortic metastases were
      present in the absence of pelvic involvement.

PMID- 10949381
TI  - The importance of colposcopy in the XXI century.

PMID- 10949382
TI  - Signal transduction and biochemical targeting of ovarian carcinoma.
AB  - The purpose was to identify novel targets for the chemotherapy of ovarian
      carcinoma. METHODS: Assays were worked out to measure the activities of P1
      kinase, PIP kinase and PLC in ovarian carcinoma samples and in OVCAR-5 cells and
      to compare the activities to those in normal ovaries. A method was also designed
      for measuring the concentration of the end product of signal transduction, IP3.
      RESULTS AND DISCUSSION: Signal transduction activity was markedly increased in
      ovarian cancer cells as shown by the increased steady-state activities of the
      three enzymes and the elevated concentrations of IP3. Inhibitors blocked
      activities of PI kinase (quercetin), PIP kinase (genistein), and lowered GTP
      concentration required for PLC (tiazofurin). Combinations of tiazofurin with
      quercetin, tiazofurin with genistein, and quercetin with genistein yielded a
      synergistic kill of ovarian cancer cells. Tiazofurin, quercetin and genistein are
      in various stages of clinical trials. CONCLUSION: The increased signal
      transduction activity provides novel, sensitive targets to chemotherapy in
      ovarian cancer cells.

PMID- 10949383
TI  - Immunohistochemical staining of the mismatch repair gene, hMSH2, and survival in
      patients with ovarian carcinoma.
AB  - OBJECTIVE: hMSH2 is a mismatch repair gene. The protein of this gene can be
      demonstrated by immunohistochemical methods. The authors wanted to analyze
      whether the percent of positive nuclear area staining of the hMSH2 protein
      correlated with survival in patients with ovarian carcinoma. METHODS: One hundred
      and two patients with epithelial ovarian carcinoma were studied. Slides were
      prepared from snap frozen tissue. Quantification of staining and DNA index were
      performed using image analysis. In addition to hMSH2, FIGO stage, grade,
      histology, and level of cytoreduction were analyzed as prognostic factors.
      RESULTS: Mean follow-up was 64 months and median was 59 months. Nineteen patients
      had stage I cancers, 4 stage II, 59 stage III, and 20 stage IV. Optimal
      cytoreduction was accomplished in 71% of patients. hMSH2 staining was
      significantly higher in better differentiated tumors (p=0.006), but there was no
      difference in staining among the FIGO stages (p=0.43). Cox regression analysis
      revealed FIGO stage (p=0.0005), level of cytoreduction (p=0.006) and hMSH2
      staining (p=0.016) to be independent predictors of survival in patients with
      ovarian carcinoma. CONCLUSION: The hMSH2 protein can be demonstrated by
      immunohistochemical methods and quantified by image analysis. hMSH2 staining was
      shown to be an independent prognostic indicator of survival in patients with
      ovarian carcinoma.

PMID- 10949384
TI  - Intensive-dose ifosfamide and etoposide with filgrastim for cytoreduction before
      peripheral blood stem cell collection in patients with advanced ovarian cancer.
AB  - OBJECTIVE: To evaluate the antitumor activity and toxic effects of intensive-dose
      ifosfamide plus etoposide with filgrastim given as stem cell mobilization therapy
      before high-dose chemotherapy for recurrent or persistent ovarian cancer.
      METHODS: We studied 32 patients with epithelial ovarian cancer who had a positive
      second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2
      (total dose) by continuous infusion over 72 h; etoposide was given at 150 mg/m2
      in 2-h infusions every 12 h during the same 72-h period; and filgrastim was given
      at 10 microg/kg/day subcutaneous injection from day 5 through completion of stem
      cell harvest. RESULTS: Nine (64%) of the 14 patients assessed responded to the
      treatment. The target stem cell dose was achieved with a median of 1 apheresis
      (range 1-5 aphereses). Nonhematologic toxicity was limited to grade 2
      nephrotoxicity in one patient and grade 2 hepatic toxicity in three patients.
      CONCLUSIONS: In this patient group, intensive-dose ifosfamide plus etoposide with
      filgrastim was well tolerated and produced antitumor activity.

PMID- 10949385
TI  - Quantitative detection of oncogenic HPV DNA using hybrid capture to triage
      borderline and mildly dyskaryotic Papanicolaou smears.
AB  - OBJECTIVE: To investigate the use of hybrid capture to triage borderline and
      mildly abnormal PAP smears to either colposcopy or continued cytological
      surveillance. METHOD: A prospective cross-sectional study of 207 women with
      either mild or borderline dyskaryosis referred to the colposcopy clinic at the
      Whittington Hospital, London was done. Quantitative detection of oncogenic human
      papillomavirus deoxyribose nucleic acid was performed using the solution
      hybridization technique Hybrid Capture I (Digene Diagnostics). Positive or
      negative hybrid capture results were compared to colposcopically directed punch
      biopsy or loop excision of the transformation zone. RESULTS: Hybrid capture
      correctly predicted 1/1 micro-invasive cancers, 23/24 CIN 3 and 20/24 CIN 2,
      giving a sensitivity to detect significant disease of CIN 2 or above of 90%. For
      CIN 1, 37/66 were HPV positive making the sensitivity to detect all grades of CIN
      70%. Of women with a normal cervix, 39/92 were HPV positive and in total 58% of
      the women were HPV positive and would have been referred to colposcopy.
      CONCLUSIONS: Hybrid capture was a simple solution hybridization method which
      provided a sensitive method of detecting CIN 2 and above lesions in women with
      minor PAP smear abnormalities. However, the sensitivity for CIN 1 and the
      specificity were low, meaning that further improvements in the technique are
      needed before it can be used as a triage strategy.

PMID- 10949386
TI  - Endometrial cancer in women 45 years of age or younger.
AB  - OBJECTIVE: The clinical characteristics and outcomes of endometrial cancer in
      women 45 years of age or younger evaluated and treated at the community hospital
      level are presented. METHODS: A series of 500 consecutive women with endometrial
      cancer operated on by the author over a nine-year period of time was used to
      identify women 45 years of age or younger and compared to older patients from the
      author's data base. RESULTS: Although the majority of patients presented with
      clinical stage I disease, 30% of women 45 years of age or younger had occult
      metastatic disease and 5.0% had clear cell or papillary serous histology, similar
      to the older patient population. In addition, survival was similar in both groups
      of patients. Serum CA-125 was useful in identifying patients with possible occult
      metastatic disease in the group of women 45 years old or younger. CONCLUSION:
      Patients 45 years of age or younger with uterine cancer are not ipso facto a
      "lower risk" group of patients; efforts to preserve fertility should be balanced
      against a thorough effort to identify those individuals at higher risk for occult
      metastases.

PMID- 10949387
TI  - Margin clearance and HPV infection do not influence the cure rates of early
      neoplasia of the uterine cervix by laser conization.
AB  - A lesion existing in the endocervical and/or ectocervical conized margin and HPV
      DNA existing in a conized specimen are reported to be at risk of persistence or
      recurrence of early neoplasia of the cervix when treated by conization. The aim
      of this study was to investigate whether margin clearance and HPV infection
      influenced the outcome in our series of laser conization. Excisional conization
      with the KTP/YAG Surgical Laser System or Nd-YAG laser was performed in this
      study. Eighty patients with cervical neoplasias were included: 47 with dysplasia,
      25 with carcinoma in situ (CIS) and eight with microinvasive carcinoma. The
      endocervical and ectocervical conized margins were examined microscopically. HPV
      DNA was analyzed with the primer for types 16, 18, 31, 33, 35, 52b and 58
      amplified by the PCR method. The margins of the conized specimens were confirmed
      histopathologically to be clear in 58 cases (73%), whereas in 22 cases (27%) they
      were involved by neoplasia. HPV-DNA was positive in 38% of dysplasias, 40% of
      CISs and 50% of microinvasive carcinomas. The overall rate of the initial cure at
      10 weeks after treatment appeared to be 100% in all 80 cases. Primary cure rates
      were 100% for 47 cases with dysplasia, 96% for 24 cases with CIS and 100% for
      four cases with microinvasive carcinoma regardless of margin positivity and HPV
      DNA status. Involved margins and HPV infection did not influence the cure of
      early neoplasia of the uterine cervix achieved by our laser conization procedure.
      The favorable results may be due to the procedure of vaporizing the cut surface
      forming a dome-shaped tissue defect.

PMID- 10949389
TI  - "Malignant struma ovarii" with peritoneal metastasis: report of two cases.
AB  - Malignant struma ovarii with metastasis in an extremely rare form of ovarian
      carcinoma. We describe two cases of malignant struma ovarii that demonstrated
      widespread peritoneal metastases. In the second case described here, furthermore,
      the tumor recurred II years later in the contralateral ovary and omentum, while
      the primary tumor previously was pure struma ovarii with no evidence of
      metastasis. Although thyroid tumors themselves are characterized by a long latent
      interval, patients with benign thyroid tissue arising in nonthyroidal organs with
      or even without dissemination should be managed with caution and need appropriate
      long-term follow-up after the initial surgery.

PMID- 10949388
TI  - Prognostic factors in platinum-resistant ovarian carcinoma treated with
      ifosfamide-etoposide.
AB  - One hundred and seven patients (median age 56) with cisplatin-resistant ovarian
      carcinomas were included in a phase II study with ifosfamide (5 g/m2) and
      etoposide (300 mg/m2) every three weeks. The first 30 patients received a 5-day
      regimen: 100 mg/m2 etoposide (i.v.) repeated in three days followed by 1 g/m2
      ifosfamide as a bolus dose in five days. Mesna 200 mg/m2 was given 0.4 and 8
      hours after each ifosfamide infusion. The next 77 patients received a 1-day
      regimen: 300 mg/m2 etoposide for two hours and then 5 g/m2 ifosfamide together
      with 5 g/mg2 mesna in 3.000 ml Ringer solution for 24 hours followed by 1 g/m2
      mesna i.v. in 100 ml Ringer solution for eight hours. Overall the objective
      response rate was 6.5% (all PR) and SD in 42% of patients with a median duration
      of six and four months, respectively. Median survival of the total group was
      seven and 12 months for the responders. One- and two-year overall survival was
      32% and 6%, respectively. Toxicity was similar in both regimens except for
      significantly more nausea and vomiting (gr 3 and 4) in groups with the 1-day
      regimen. There were few serious effects and they were manageable. Multivariate
      analysis identified degree of differentiation and response to
      ifosfamide/etoposide as the two most powerful prognostic factors of overall
      survival (p=0.0004 and p=0.0018, respectively). In conclusion, the therapeutic
      index of ifosfamide/etoposide treatment was very low and in this subset of
      ovarian cancer patients with platinum resistance and should be abandoned.

PMID- 10949390
TI  - Radiotherapy for cancer of the cervix in morbidly obese women: preliminary
      results.
AB  - A retrospective four-year review showed that six morbidly obese (> or = 40 kg/m2)
      women, two of whom underwent pre-irradiation simple hysterectomy, were
      definitively treated with radiation for cancer of the cervix. All cases were FIGO
      stage IB. The average age was 49 years and average body mass index 49 kg/m2.
      Radiotherapy consisted of external beam pelvic irradiation and low-dose rate or
      high-dose rate brachytherapy applications. During a follow-up period ranging from
      9 to 46 months, all women were alive and free of neoplastic disease as well as
      complications. Albeit long-term outcome data are not yet available, we believe
      that morbidly obese women with early stage cervical cancer who are not suitable
      candidates for curative surgery may derive beneficial effects from appropriately
      applied definitive radiotherapy.

PMID- 10949391
TI  - Cervicography to triage women with borderline or mild dyskaryotic cervical PAP
      smears.
AB  - OBJECTIVE: To evaluate six years experience using cervicography to triage women
      with borderline or mildly dyskaryotic PAP smears to either immediate colposcopy
      or cytological surveillance. METHOD: Retrospective study of 1,436 women referred
      to the cervicography clinic of the Whittington Hospital, London. Women with
      suspicious cervigrams were examined colposcopically and biopsied. Women with
      normal appearances at cervicography were followed-up with cytology over a period
      of a least two years. RESULTS: Cervicography detected 281 out of 307 women with
      CIN 2/3 and 215 out of 264 women with CIN 1. The sensitivity of cervicography to
      detect CIN 1, 2 or 3 in women with minor PAP smear abnormalities was 92%. The
      specificity was 39% and 847 (59%) of the women were referred for colposcopy; 215
      (15%) were lost to follow-up. CONCLUSIONS: Cervicography was a sensitive method
      to detect CIN in women with mild or borderline dyskaryosis on their PAP smears.
      However, the low specificity meant that a high proportion of the women were
      referred for colposcopy, and a significant proportion of women were lost to
      follow-up. Thus cervicography is not an efficient strategy for managing women
      with minor PAP smears abnormalities.

PMID- 10949392
TI  - Prognostic value of bcl-2, p53 and Ki-67 in invasive squamous carcinoma of the
      uterine cervix.
AB  - The aim of this study was to evaluate the immunohistochemical expression of the
      markers bcl-2, p53 and Ki67 and their relation to the classical clinical
      pathological prognostic factors in invasive squamous cellular carcinoma of the
      cervix. Since bcl-2 and p53 are implicated in the regulation of programmed cell
      death, very probably they play a role in carcinogenesis and consequently become
      prognostic factors.

PMID- 10949393
TI  - Analysis of the DNA "mismatch-repair" enzyme human mut-S-homologon-2 in
      endometrial cancer on protein- and RNA-level.
AB  - BACKGROUND: Microsatellite instability seems to be important in the development
      of various human cancers including sporadic endometrial cancer and is
      characterized by length changes at repetitive loci scattered throughout the
      genome. It has been shown that cancer predisposition is attributable to defects
      in any one of four genes, all of which encode homologs of the microbial mismatch
      repair proteins mutS and mutL. The human Mut-S-Homologon-2 gene (hMSH-2)
      specifies a mutS homolog, whereas hMLH-1, hPMS-1 and hPMS-2 encode homologs of
      mutL. MATERIAL AND METHODS: Freshly excised endometrial specimens (malignancies
      of the uterine corpus: n=50; normal endometrial tissue: n=20) were examined by
      immunohistochemistry (mAb FE 11, Dianova, Germany) and RT-PCR to analyze the
      expression of human MUT-S-Homologon-2 on protein- and mRNA-level. Most of the
      neoplasms of the uterine corpus were sporadic endometrial. RESULTS: In the
      immunohistochemical study, 25% of normal endometrial tissues were human Mut-S
      Homologon-2 negative, while the remaining 75% revealed weak human Mut-S-Homologon
      2 immunoreactivity (mean human Mut-S-Homologon-2 IRS: 1.52; SD: +/-1.42; mean
      human Mut-S-Homologon-2-PP: 12.12; SD: +/-10.31; mean human Mut-S-Homologon-2 IS:
      0.98; SD: +/-0.81). All malignancies of the uterine corpus revealed strong
      nuclear immunoreactivity for human Mut-S-Homologon-2 (mean human Mut-S-Homologon
      2-IRS: 9.12, SD: +/-3.34; mean human Mut-S-Homologon-2-PP: 81.82, SD: +/-15.67;
      mean human Mut-S-Homologon-2-IS: 2.58, SD: +/-0.71). In addition, expression of
      human Mut-S-Homologon-2 protein was statistically significantly upregulated in
      tumor cells of malignancies of the uterine corpus as compared to normal
      endometrial tissue on the protein level. In the RT-PCR study, the hMSH-2 gene was
      highly expressed in endometrial neoplasms on the mRNA-level. hMSH-2 expression
      was consistently increased in endometrial neoplasms compared to normal
      endometrial tissue. CONCLUSION: The expression of the human MUT-S-Homologon-2 is
      increased both on the protein- and on mRNA-level in endometrial neoplasms
      compared to normal endometrial tissue possibly caused by the neoplastic process
      driven by an increase in the rate of mutations in oncogenes and tumor suppressor
      genes.

PMID- 10949394
TI  - Prognostic significance of tissue DF3 antigen and CA15-3 tumor marker in primary
      breast cancer.
AB  - The specific monoclonal antibody, DF3, for breast cancer and the corresponding
      tumor marker CA15-3 were evaluated in 108 patients with primary cancer of the
      breast. These antigens correlated poorly with the known prognostic parameters.
      Elevated CA15-3 serum values were associated with the cytoplasmic distribution of
      the DF3 antigen in the cell. The DF3 distribution pattern and the CA15-3 serum
      values had prognostic significance for disease-free interval.

PMID- 10949395
TI  - Prognostic significance of deletion and over-expression of the p53 gene in
      epithelial ovarian cancer.
AB  - PURPOSE OF INVESTIGATION: To define the deletion or over-expression of p53 genes
      and their prognostic significance in epithelial ovarian cancers. METHODS: A total
      of 26 patients with epithelial ovarian cancer, who had undergone second-look
      laparotomy after primary surgery and six courses of platinum-based chemotherapy
      were included in the study. Paraffin-embedded archival tissue samples of all
      cases were examined for deletion and over-expression of p53 gene by FISH and
      immunohistochemical methods, respectively. The relation between these findings
      and clinico-pathological prognosticators or survival of the patients were
      analyzed by the Fisher Exact chi2 test, Cox regression model and life table
      analysis. RESULTS: p53 gene deletion, related to single or double allele, was
      determined in all cases with a range of 6% to 75% of the cancer cells. When 40%
      was accepted as the cut-off ratio for the deletion rate, seven (26.9%) of the
      cases were observed to have p53 deletion. Although p53 over-expression was
      defined in 12 (46.1%) patients, four of whom were also accompanied by p53
      deletion, there was no relation between the p53 deletion and over-expression
      (p>0.05). p53 deletion was also not related to any prognostic factors or survival
      of the patients (p>0.05). However, cases with p53 over-expression had
      significantly more advanced stage and higher-grade tumors, and shorter median
      survival (p>0.05-0.01). CONCLUSION: p53 gene mutation determined by over
      expression of p53 protein has been suggested as an important prognostic factor
      for epithelial ovarian cancer, however, it has not always been accompanied by p53
      deletion.

PMID- 10949396
TI  - Sarcomatoid squamous cell carcinoma of the uterine cervix: case report.
AB  - Sarcomatoid squamous cell carcinoma (SSCC) is a recognized entity, usually
      involving the upper aerodigestive tract and skin. Location in the lower female
      genital tract is rare. Only 11 cases have been previously reported, four of which
      arose in the uterine cervix. The authors describe the case of a 39-years-old
      woman with SSCC of the uterine cervix in Stage I of the International Federation
      of Gynecology and Obstetrics (F.I.G.O.) classification. The patient died of
      disease 12 months after diagnosis. Similar cases described in the literature are
      also reviewed.

PMID- 10949397
TI  - Liposarcoma of the uterine cervix: case report.
AB  - A case of primary liposarcoma of the cervix is described in a 49-year-old woman
      with a fungating cervical mass which was diagnosed as liposarcoma on the basis of
      cytologic features and the intracellular lipids. Most of the adipocytes and
      vacuolated lipoblasts were positive for S- 100 protein. The mass was well
      circumscribed and limited to the superficial cervical stroma. A total abdominal
      hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy was
      performed. There was no clinical evidence of metastasis two years after the
      operation.

PMID- 10949398
TI  - Carcinosarcoma of the uterine cervix composed of an adenoid cystic carcinoma and
      an homologous stromal sarcoma. A case report.
AB  - A case of primary cervical carcinosarcoma is presented. The tumor occurred in a
      76-year-old multiparous woman and it replaced the uterine cervix, extending to
      the vaginal wall and to the uterine corpus. Histologically, the carcinomatous
      component was exclusively an adenoid-cystic carcinoma and the sarcomatous
      component was an homologous stromal sarcoma. Immunohistochemically, both the
      carcinomatous and the sarcomatous elements were stained with smooth muscle actin.
      Only two other similar cases have been reported.

PMID- 10949399
TI  - Malignant melanoma of the vagina. A report of 15 cases.
AB  - Twenty patients affected by vaginal malignant melanoma, 15 of which were
      evaluable for outcome, were observed from 1969 to 1993. Two patients died
      postoperatively, nine patients developed recurrences and four patients had no
      disease-free period. All patients died of their disease and the median overall
      survival was 19 months. The natural history of vaginal malignant melanoma differs
      from that of the skin with a more aggressive behaviour. Primary treatment should
      be wide local excision of the tumor.

PMID- 10949400
TI  - Ovarian cancer epidemiology in Thrace, Greece.
AB  - PURPOSE OF INVESTIGATION: To report the differences in ovarian cancer prevalence
      between the two major ethnic groups (Christian Orthodox and Muslims) in Thrace,
      Greece. METHOD: We carried out a retrospective study on 57 patients, aged 16-79
      years, who were treated in our clinic for ovarian cancer. RESULTS: The cumulative
      ovarian cancer prevalence in Thrace was 6.8/100,000 (5.5/100,000 for Christian
      Orthodox and 1.3/100,000 for Muslims). There were no statistically significant
      differences in most variables affecting the tumour itself. The statistical
      analysis of demographic risk factors revealed that the Christian population was
      more of a middle class profile, while the Muslim lifestyle sustained its cultural
      characteristics, a difference that could be related to the discrepancy observed
      in ovarian cancer prevalence among them. CONCLUSIONS: The overall ovarian cancer
      prevalence in Thrace is lower than that reported for most developed countries and
      higher than that for most Asian countries. The variance in prevalence between
      Christian Orthodox and Muslims could possibly be attributed to the different
      major parameters in lifestyles.

PMID- 10949401
TI  - Effect of adjuvant chemotherapy using pirarubicin, cisplatin, and etoposide (PEP)
      for stage IVB endometrial carcinoma: a case report.
AB  - Prognosis of patients with stage IVB endometrial adenocarcinoma is quite poor.
      Combination therapy of radiation with surgery or chemotherapy is a common therapy
      for advanced endometrial cancers. However, radiation therapy is effective only
      for localized cancer, and the chemotherapeutic effect on stage IVB endometrial
      cancers is very low. We present a patient with stage IVB endometrial
      adenocarcinoma, whose tumor was not resected completely at the first surgery. She
      showed a remarkable response to a PEP (pirarubicin, etoposide, cisplatin) regimen
      and has survived without disease over 8 years. This case suggests that reduction
      surgery following PEP therapy is a new therapeutic modality for stage IVB
      endometrial carcinoma.

PMID- 10949402
TI  - Hormonal modulation of GM-CSF receptor alpha-chain in in vitro models of
      endometrial cancer.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that
      stimulates the proliferation and differentiation of bone marrow progenitors.
      Moreover, the presence and activity of GM-CSF and its receptor (GM-CSF-r) has
      been documented on tissues and cell lines of a non-hemopoietic origin. In this
      paper we studied the expression and putative role of GM-CSF and GM-CSF-r in
      endometrial cancer. The modulation of GM-CSF-r alpha-chain upon progesterone
      treatment suggests a role for GM-CSF and its receptor in the pathogenesis and
      development of endometrial cancer.

PMID- 10949403
TI  - Synchronous endometrial carcinosarcoma and breast carcinoma: a case report.
AB  - The association of breast and uterine carcinoma has been demonstrated by many
      authors. However, these double primaries with endometrial cancer having
      pathologic features of a carcinosarcoma are a very rare phenomena. Moreover, most
      of the cases are related to the previous use of tamoxifen for the treatment of
      breast carcinoma. In the present study we describe a case of an endometrial
      carcinosarcoma and a synchronous adenocarcinoma of the breast.

PMID- 10949405
TI  - Primary gastric choriocarcinoma: case report.

PMID- 10949404
TI  - Postoperative radiotherapy in endometrial carcinoma: analysis of prognostic
      factors in 440 cases.
AB  - PURPOSE: The aim of this study was to determine the prognostic factors
      influencing overall, disease-free and local recurrence-free survival in patients
      treated postoperatively with adjuvant radiotherapy for endometrial carcinoma.
      METHODS: The records of 440 patients with endometrial carcinoma treated by
      postoperative radiotherapy between January 1985 and June 1997 were reviewed
      retrospectively. All patients received postoperative external radiotherapy with
      1.8-2.0 Gy daily fractions up to 36-68 Gy (median 54 Gy). Intracavitary
      brachytherapy was applied to 61.8% of the cases. Survival analysis was performed
      using the Kaplan-Meier method. The log-rank test was used for univariate analysis
      and the Cox regression model for multivariate analysis. RESULTS: Median age of
      the patients was 57 (range: 35-83). Histologically 80.2% were adenocarcinoma,
      5.7% adenosquamous carcinoma, 5.2% clear-cell carcinoma and 4.3% serous papillary
      carcinoma. The distribution by stages were: 62.2% Stage I, 20.0% Stage II, 14.9%
      Stage III, 2.8% Stage IV. Median follow-up time was 53 months (7-173 months).
      Total failure rate was 15.2% with 2.7% of patients having only local failure,
      2.0% local and distant failure and 10.5% distant failure only. Five-year overall,
      disease-free and local recurrence-free survival rates were 81.6%, 80.7% and
      94.6%, respectively. According to univariate analysis prognostic factors
      influencing disease-free survival were histologic type (p=0.0067), histologic
      grade (p=0.0015), stage (p<0.0001), myometrial invasion (p<0.0001), peritoneal
      cytology (p=0.0013) and cervical involvement (p=0.0106) while the prognostic
      factors affecting local recurrence-free survival were stage (p=0.0277),
      myometrial invasion (p=0.0054), peritoneal cytology (p=0.0427). According to
      multivariate analysis prognostic factors influencing disease-free survival were
      histologic type (p=0.0194), myometrial invasion (p=0.0021), and histologic grade
      (p=0.0303) while the only prognostic factor influencing local recurrence-free
      survival was myometrial invasion (p=0.0241). CONCLUSION: Radiotherapy is a highly
      effective adjuvant treatment providing an excellent locoregional control rate and
      it should be continued for patients with unfavorable prognostic factors.

PMID- 10949406
TI  - Leiomyosarcoma of the broad ligament: case report and literature review.
AB  - A 56-year-old woman with leiomyosarcoma of the broad ligament discovered in the
      outpatient clinic in Marmara University Medical School is presented. Treatment
      consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy.
      After a one-year disease-free interval, the patient underwent a repeat laparotomy
      and recurrence of the previously excised malignant tumor was removed. The patient
      received external radiotherapy to the pelvis with linear accelerator.

PMID- 10949407
TI  - Low dose responses.

PMID- 10949408
TI  - Assessing and managing risks in a democratic society. Making sense of risk.

PMID- 10949409
TI  - Assessing and managing risks in a democratic society. Risk, democracy, and the
      environment

PMID- 10949410
TI  - Assessing and managing risks in a democratic society. Markets to master health
      and environmental risk.

PMID- 10949411
TI  - The tumorigenicity of mutagenic contact-sensitizing chemicals.
AB  - The electrophilic nature of some contact sensitizers, that is, chemicals that
      cause allergic contact dermatitis (ACD), is also characteristic of genotoxic
      tumorigens. Electrophiles can adduct protein, which is the basis for ACD, as well
      as DNA, which is the basis for mutagenicity and carcinogenicity. This suggests
      that some electrophilic contact sensitizers may be genotoxic tumorigens. To
      further investigate this matter, we evaluated 146 chemicals that had been
      bioassayed for tumorigenicity and mutagenicity in the National Toxicology
      Program, with an analysis of structure-activity relationships for contact
      sensitization. Using the data from this analysis and from other sources, the
      proportion of the contact sensitizers that were both mutagenic and tumorigenic
      was found to range from 20% to 28%. This finding suggests that there may be in
      the order of 90 genotoxic tumorigens for rodents among the approximately 384
      chemicals that have been validated as contact sensitizers for humans.

PMID- 10949412
TI  - A probabilistic methodology for the assessment of safety from dropped loads in
      offshore engineering
AB  - Pipeline damage by dropped objects from crane activities is a significant hazard
      for offshore platform installations. In this paper a probabilistic methodology is
      utilized for the estimation of the pipeline impact and rupture frequencies; this
      information is obtained both for the overall pipeline section exposed to the
      hazard and for a number of critical locations along the pipeline route. The
      presented algorithm has been implemented in a computer program that allows the
      analysis of a large number of possible drop points and pipeline target point
      locations. This methodology may be used in common risk analysis studies for
      evaluating the risk for platform personnel from dropped objects; however, the
      proposed technique may also be useful for other applications where engineering
      judgment has so far been the main driving criterion. In particular, two sample
      cases have been analyzed. The first one is the problem of selecting the best
      approaching route to a platform. By analyzing different route alternatives, a
      reduction of the impact frequency and therefore of the risk for the platform
      personnel may be achieved. The second application deals with the selection of the
      location for a safety valve at the riser base. The analysis may give useful
      information, such as the highest impact frequency location and the rupture
      frequencies upstream and downstream of the valve as a function of the valve
      position; this information, together with the transported medium inventory
      upstream of the valve, may give the designer a documented and justifiable
      rationale for selecting the best location for the valve from a safety point of
      view.

PMID- 10949413
TI  - Setting risk priorities: a formal model
AB  - This article presents a model designed to capture the major aspects of setting
      priorities among risks, a common task in government and industry. The model has
      both design features, under the control of the rankers (e.g., how success is
      evaluated), and context features, properties of the situations that they are
      trying to understand (e.g., how quickly uncertainty can be reduced). The model is
      demonstrated in terms of two extreme ranking strategies. The first, sequential
      risk ranking, devotes all its resources, in a given period, to learning more
      about a single risk, and its place in the overall ranking. This strategy
      characterizes the process for a society (or organization or individual) that
      throws itself completely into dealing with one risk after another. The other
      extreme strategy, simultaneous risk ranking, spreads available resources equally
      across all risks. It characterizes the most methodical of ranking exercises.
      Given ample ranking resources, simultaneous risk ranking will eventually provide
      an accurate set of priorities, whereas sequential ranking might never get to some
      risks. Resource constraints, however, may prevent simultaneous rankers from
      examining any risk very thoroughly. The model is intended to clarify the nature
      of ranking tasks, predict the efficacy of alternative strategies, and improve
      their design.

PMID- 10949414
TI  - Salient value similarity, social trust, and risk/benefit perception
AB  - It was postulated that shared values determine social trust in institutions and
      persons related to a technology: One has trust in people holding similar salient
      values. Furthermore, it was hypothesized that social trust has a positive
      influence on perceived benefits and a negative impact on perceived risks. Results
      of a survey of University of Zurich students indicated that the proposed causal
      model explained perception of pesticides, nuclear power, and artificial sweetener
      very well. When social trust was controlled, the relation between risks and
      benefits perceived diminished. Results indicate that social trust is a key
      predictive factor of the perceived risks and benefits of a technology, and
      provide support for the salient values similarity theory of social trust.

PMID- 10949415
TI  - Regression models and risk estimation for mixed discrete and continuous outcomes
      in developmental toxicology.
AB  - Multivariate dose-response models have recently been proposed for developmental
      toxicity data to simultaneously model malformation incidence (a binary outcome),
      and reductions in fetal weight (a continuous outcome). In this and other
      applications, the binary outcome often represents a dichotomization of another
      outcome or a composite of outcomes, which facilitates analysis. For example, in
      Segment II developmental toxicology studies, multiple malformation types (i.e.,
      external, visceral, skeletal) are evaluated on each fetus; malformation status
      may also be ordinally measured (e.g., normal, signs of variation, full
      malformation). A model is proposed is for fetal weight and multiple malformation
      variables measured on an ordinal scale, where the correlations between the
      outcomes and between the offspring within a litter are taken into account. Fully
      specifying the joint distribution of outcomes within a litter is avoided by
      specifying only the distribution of the multivariate outcome for each fetus and
      using generalized estimating equation methodology to account for correlations due
      to litter clustering. The correlations between the outcomes are required to
      characterize joint risk to the fetus, and are therefore a focus of inference.
      Dose-response models and their application to quantitative risk assessment are
      illustrated using data from a recent developmental toxicology experiment of
      ethylene oxide in mice.

PMID- 10949416
TI  - Quantitative methods for environmental justice assessment of transportation
AB  - Application of Executive Order 12898 to risk assessment of highway or rail
      transport of hazardous materials has proven difficult; in general, the location
      and conditions affecting the propagation of a plume of hazardous material
      released in a potential accident are unknown. Therefore, analyses have only been
      possible in a geographically broad or approximate manner. The advent of
      geographic information systems and development of software enhancements at Sandia
      National Laboratories have made kilometer-by-kilometer analysis of populations
      tallied by U.S. Census blocks along entire routes practicable. Tabulations of
      total or racially/ethnically distinct populations close to a route, its
      alternatives, or the broader surrounding area, can then be compared and
      differences evaluated statistically. This article presents methods of comparing
      populations and their racial/ethnic compositions using simple tabulations,
      histograms, and chi-square tests for statistical significance of differences
      found. Two examples of these methods are presented: comparison of two routes and
      comparison of a route with its surroundings.

PMID- 10949417
TI  - Evaluating the simplified Conjoint Expected Risk model: comparing the use of
      objective and subjective information
AB  - The simplified Conjoint Expected Risk (CER) model by Holtgrave and Weber posits
      that perceived risk is a linear combination of the subjective judgments of the
      probabilities of harm, benefit, and status quo, and the expected harm and benefit
      of an activity. It modifies Luce and Weber's original CER model--that uses
      objective information to evaluate financial gambles--to accommodate activities
      such as health/technology activities where values of the model variables are
      subjective. If the simplified model is a valid modification of the original
      model, its performance should not be sensitive to the use of subjective
      information. However, because people may evaluate information differently when
      objective information is provided to them than when they generate information on
      their own, the performance of the simplified CER model may not be robust to the
      source of model-variable information. We compared the use of objective and
      subjective information, and results indicate that the estimates of the simplified
      CER model parameters and the proportion of variance in risk judgments accounted
      for by the model are similar under these two conditions. Thus, the simplified CER
      model is viable with activities for which harm and benefit information is
      subjective.

PMID- 10949418
TI  - Utility of Biochemical Systems Theory for the analysis of metabolic effects from
      low-dose chemical exposure.
AB  - Adverse health outcomes from exposure to chemical agents are of increasing
      interest in human and ecological risk assessment and require the development of
      new analytical methods. Such methods must be able to capture the essence of
      integrated networks of biochemical pathways in a mathematically feasible fashion.
      Over the past three decades, Biochemical Systems Theory has been successfully
      applied to numerous biological systems. It is suggested here that S-system models
      derived from BST can provide the means for assessing chemical exposures and their
      effects at the metabolic level. This article briefly reviews essential concepts
      of S-systems and provides generic examples of chemical exposure scenarios. S
      system models can be considered mechanistic, since their components are
      measurable quantities (e.g., concentrations, fluxes, enzyme activities, and
      rates). As dynamic models, they can be used to assess immediate and long-term
      metabolic responses to environmental stimuli. Direct mathematical analysis for
      low exposures leads to simple dose-response relationships, which have the form of
      power-law functions. Thus, if the S-system model yields an appropriate
      description of chemical exposure and its metabolic effects, the dose-response
      relationship for low exposures is linear in logarithmic coordinates. This result
      includes as a special case the standard linear relationship in Cartesian
      coordinates with zero intercept.

PMID- 10949419
TI  - Urinary tract masses.
AB  - Disorders of the urinary tract account for the majority of abdominal masses in
      infants. The most common causes of a flank mass in a neonate are a hydronephrotic
      kidney followed by a multicystic kidney. An increasing number of disorders
      resulting in hydronephrosis are diagnosed by prenatal ultrasound scan, and their
      natural history continues to be elucidated. This review will examine the common
      anatomic and functional causes of fetal and neonatal hydronephrosis as well as
      the diagnosis and treatment of solid and cystic urinary tract masses.

PMID- 10949420
TI  - Prune belly syndrome.
AB  - Prune belly is a lax, wrinkled abdominal wall and frequently is associated with
      other anomalies. The prune belly syndrome is a specific constellation of
      anomalies consisting of an abdominal wall deficient in muscular tissue, dilated
      urinary tract, and bilateral cryptorchidism. This group of anomalies is also
      called the Eagle-Barrett syndrome and the triad syndrome. In about 3 of 4
      patients with the prune belly syndrome, there are associated malformations of the
      cardiopulmonary, gastrointestinal, and orthopedic systems.

PMID- 10949421
TI  - Ovarian masses in the newborn.
AB  - Prenatal sonography uncovers many fetal ovarian masses that previously would have
      gone unrecognized. This challenges clinicians to learn the natural history of
      these asymptomatic lesions so as to provide the best care postnatally.
      Spontaneous resolution of simple ovarian cysts is expected by about 6 months of
      age, which is attributed to predicted changes in the postnatal hormonal milieu.
      After birth, levels of human chorionic gonadotropin (HCG) and estrogen plummet.
      Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) rise until about
      3 months of age and then fall as the "gonadostat" matures. Although symptomatic
      cysts demand intervention, simple asymptomatic cysts less than 5 cm in diameter
      should be left alone but reassessed sonographically. If simple cysts are larger
      than 5 cm in diameter the risk of torsion may be significant, and intervention
      often is advocated. However, the risk of torsion versus the likelihood of
      resolution is not well established. The therapeutic goal for a clinician managing
      a newborn with a simple ovarian cyst is to maximize ovarian salvage. Aspiration
      alone may be a reasonable option. The laparascopic approach to the neonatal
      ovarian cyst provides a view of both ovaries and allows aspiration, unroofing,
      cystectomy, or ovariectomy. The sonographically complex cyst usually represents
      adnexal torsion but could be a neoplasm and warrants intervention because the
      morbidity from untreated neonatal adnexal torsion can be significant beyond loss
      of the ovary (eg, hemorrhage, peritonitis, intestinal obstruction, or a wandering
      tumor).

PMID- 10949422
TI  - Vaginal obstruction.
AB  - Congenital anomalies that result in vaginal obstruction often present with an
      abdominal mass in the newborn period. Knowledge of the embryological development
      of the genitourinary tract and its variations is needed to properly evaluate the
      neonatal patient and to initiate therapy. Because of a high incidence of
      associated anomalies, a complete urologic evaluation should be undertaken before
      a definitive surgical repair. The methods of treatment for the various causes of
      vaginal atresia have shown long-term success and have resulted in appropriate
      psychosocial and sexual maturation.

PMID- 10949423
TI  - Gastrointestinal duplications.
AB  - Gastrointestinal duplications are rare congenital lesions that can develop
      anywhere along the alimentary tract and may present in the newborn period as an
      abdominal mass. They are differentiated from other intraabdominal cystic lesions
      by the presence of a normal gastrointestinal mucosal lining. Multiple theories
      have been proposed to account for these lesions; however, no single theory
      adequately explains all the known duplications. They are most frequently single,
      tubular, or cystic and located on the mesenteric side of the native alimentary
      tract structure. Symptoms often are related to the location of the duplication;
      oral and esophageal lesions can create respiratory difficulties, whereas lower
      gastrointestinal lesions may cause nausea, vomiting, bleeding, perforation, or
      obstruction. Treatment is resection with care taken to protect the common blood
      supply of the native structures. Occasionally, a partial resection with mucosal
      excision is required to preserve intestinal mucosa.

PMID- 10949424
TI  - Newborn intraabdominal cystic lymphatic malformations.
AB  - Cystic lymphatic malformations are rare causes of abdominal masses in the
      newborn. Also known as mesenteric, omental, or retroperitoneal cysts, they can
      present in a variety of ways including, intestinal obstruction, volvulus,
      nonspecific abdominal pain, intracystic hemorrhage, or as an asymptomatic
      abdominal mass. Abdominal ultrasound scan provides a definitive diagnosis in most
      suspected cases. Complete resection is possible in most patients except those
      with extensive retroperitoneal involvement. Recurrence is unusual when complete
      resection is accomplished. Because most case series with complete data suggest
      that these entities are lymphatic malformations, the authors suggest the more
      specific term, cystic lymphatic malformations, be used to describe these lesions.

PMID- 10949425
TI  - Benign liver and biliary tract masses in infants and toddlers.
AB  - There is a remarkable diversity of conditions encompassed by benign liver masses
      in infants and toddlers. The most common benign hepatic tumor in this age group
      is infantile hepatic hemangioendothelioma. Other commonly seen benign tumors are
      mesenchymal hamartoma and focal nodular hyperplasia. Hepatic adenoma is almost
      exclusively a disease of older children; primary hepatic teratoma is exceedingly
      rare. There are several distinguishing characteristics of these benign tumors on
      radiographic evaluation; however, imaging techniques such as ultrasound scan,
      computed tomography, and angiography are not always reliable in differentiating
      benign from malignant tumors. The differential diagnosis of benign hepatic tumors
      includes nonneoplastic cystic masses including biliary and simple hepatic cysts,
      hematoma, parasitic cysts, and pyogenic and amebic liver abscess. Choledochal
      cyst presents with a classic triad of abdominal pain, cholestatic jaundice, and a
      palpable abdominal mass. They are classified anatomically into 5 subtypes with
      the most popular types being type I and type IV. Treatment is with complete cyst
      excision with hepaticojejunostomy reconstruction.

PMID- 10949426
TI  - Adrenal masses in the newborn.
AB  - The incidence of neonatal adrenal tumors is increasing due to the expanded use
      and accuracy of prenatal ultrasonography in routine obstetric care. Although
      adrenal and juxtarenal masses may represent benign lesions (adrenal hemorrhage,
      subdiapragmatic extralobar pulmonary sequestration), the majority of masses
      either are premalignant or malignant. Previous algorithms for the diagnosis and
      management of these lesions have been guided primarily by the high incidence of
      neuroblastomas within this group. Improved insight into the relatively benign
      behavior of many neonatal neuroblastomas has stimulated debate regarding the
      appropriate management schema for neonatal adrenal masses. Moreover, the
      increasing recognition of benign juxtarenal lesions further challenges the
      conventional dogma. This review discusses the major categories of adrenal masses
      to help generate a rational algorithm for diagnosis and therapy.

PMID- 10949427
TI  - A model of the transmission and control of genital herpes.
AB  - BACKGROUND: Mathematical modeling of herpes simplex virus type 2 transmission can
      provide insight into the behavior of the epidemic and the effects of control
      measures. GOAL: To examine parameter sensitivity and assess control strategies.
      STUDY DESIGN: The model simulates transmission in a young, sexually active,
      nonmonogamous population. The population is divided into compartments
      representing disease status (susceptible, exposed, primary infectious,
      asymptomatic, recurrent, vaccinated), and flows between compartments are
      described by differential equations. RESULTS: With a base set of parameter
      values, the basic reproduction rate (R0) is 1.79, indicating that ultimate
      prevalence in this population will be 44%. The course of the epidemic is most
      sensitive to changes in behavioral parameters (time nonmonogamous and partner
      change rate) and to the probability of transmission during the asymptomatic
      stage. CONCLUSION: In the absence of behavior change, efforts to control the
      epidemic must focus on vaccine development and prevention of transmission during
      both symptomatic and asymptomatic phases.

PMID- 10949428
TI  - How effective is syndromic management of STDs?: A review of current studies.
AB  - BACKGROUND: Studies of the accuracy of syndromic management have demonstrated
      widely varying results depending upon gender, location of infection, risk group,
      organisms, among other factors. GOAL: To review current knowledge about syndromic
      management of sexually transmitted diseases (STDs) and to make recommendations
      about the strengths and weaknesses of different syndromic management algorithms.
      STUDY DESIGN: The authors identified articles and abstracts about the syndromic
      management of STDs. Evaluation of the effectiveness of algorithms for urethral
      discharge, genital ulcer disease, and vaginal discharge was based primarily on
      published sensitivity and specificity data. RESULTS: Overall, algorithms for the
      diagnosis and treatment of urethral discharge and genital ulcer disease in men
      had high sensitivities or cure rates (urethral discharge, 87-99%; genital ulcer
      disease, 68-98%). The sensitivities for the algorithms for vaginal discharge
      ranged from 73% to 93% among women presenting with symptoms of vaginal discharge,
      and from 29% to 86% among women not presenting with symptoms. Vaginal discharge
      was not found to be an effective indicator of cervical infection and, therefore,
      is not an independently effective screening tool to detect women with cervical
      infection, especially in low-risk or asymptomatic populations. Incorporating risk
      scores can improve the accuracy of algorithms to detect cervical infection.
      CONCLUSIONS: Algorithms for urethral discharge and genital ulcer disease can be
      effective in STDs. The current algorithms for vaginal discharge are not highly
      effective in detecting gonorrhea and chlamydia in women; risk scores can improve
      their efficacy, but must be tailored to reflect community risks. Without
      attention to the qualitative aspects of STD syndromic management, these methods
      will likely have even less accuracy than the studies reviewed above. There
      remains an urgent need for the development of an affordable, rapid, and effective
      diagnostic technique that will improve STD detection in resource-poor settings.

PMID- 10949429
TI  - Sexually transmitted diseases in a family planning and an antenatal clinic in
      Peru: limitations of current practices and analysis of the use of potential
      markers, pH testing, and Whiff testing.
AB  - BACKGROUND: Little data exist on sexually transmitted diseases (STDs), including
      HIV, in family planning and antenatal clinics in Peru. GOAL: To evaluate (1) the
      prevalence of infection, (2) associated factors, (3) current clinical practices,
      and (4) the sensitivity of whiff and pH testing for STDs. STUDY DESIGN: A study
      of 363 women from an antenatal (n = 259) and a family planning (n = 104) clinic
      in central Lima, Peru that included oral histories and physical examinations.
      Samples were collected for laboratory diagnosis of common STDs, including HIV.
      RESULTS: Overall, 10.8% of antenatal clinic patients and 15.4% of family planning
      clinic patients had an STD, but no HIV infection was found. The diagnostic
      sensitivity of health providers was low, especially for cervical infections
      (sensitivity, 0%). In addition, few factors were associated with cervical
      infections or trichomoniasis. In the family planning clinic, pH testing was 100%
      sensitive for trichomoniasis and bacterial vaginosis. In both clinics, whiff
      testing was 84% sensitive and 47% specific for trichomoniasis and 88% sensitive
      and 53% specific for bacterial vaginosis. CONCLUSION: The burden of STDs was high
      and the sensitivity of current diagnostic practices was low. These results point
      to the need for simple diagnostic tools. Whiff and pH testing was found
      potentially useful for the diagnosis of vaginal infections. These simple tests
      should be implemented as screening tools.

PMID- 10949430
TI  - Prevalence and correlates of herpes simplex virus type 2 infection in a
      population-based survey of young women in low-income neighborhoods of Northern
      California. The Young Women's Survey Team.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) is one of the most common
      sexually transmitted infections and may enhance transmission of HIV. However,
      population-based estimates of HSV-2 prevalence and correlates of infection are
      rare. GOALS: To obtain population-based estimates of HSV-2 prevalence and to
      identify demographic and sexual behavioral correlates of infection among women in
      low-income communities of Northern California. STUDY DESIGN: A randomized, single
      stage, cluster sample, cross-sectional survey of women age 18 to 29 years who
      reside in 1990 US Census block groups at the lowest tenth percentile for
      household income. RESULTS: The survey-weighted prevalence of HSV-2 infection was
      34.8% (95% CI, 30.4-39.2). Factors independently associated with HSV-2
      seropositivity were black race, older age, lower income, parity, greater number
      of lifetime male sexual partners, earlier onset of sexual intercourse, sex work,
      history of sexually transmitted disease (STD), and cocaine use. CONCLUSION: The
      high prevalence of HSV-2 and the strong correlation with sexual risk underscores
      the potential for further spread of STD, including HIV, in this young population.

PMID- 10949431
TI  - Improvement of clinical algorithms for the diagnosis of Neisseria gonorrhoeae and
      Chlamydia trachomatis by the use of Gram-stained smears among female sex workers
      in Accra, Ghana.
AB  - BACKGROUND: Screening for cervical infection is difficult in developing
      countries. Screening strategies must be improved for high-risk women, such as
      female sex workers. GOAL: To evaluate the sensitivity and specificity of
      screening algorithms for cervical infection pathogens among female sex workers in
      Accra, Ghana. STUDY DESIGN: A cross-sectional study among female sex workers was
      conducted. Each woman underwent an interview and a clinical examination. Biologic
      samples were obtained for the diagnosis of HIV, syphilis, bacterial vaginosis,
      yeast infection, Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia
      trachomatis infection. Signs and symptoms associated with cervicitis agents were
      identified. Algorithms for the diagnosis of cervical infection were tested by
      computer simulations. RESULTS: The following prevalences were observed: HIV,
      76.6%; N. gonorrhoeae, 33.7%; C. trachomatis, 10.1%; candidiasis, 24.4%; T.
      vaginalis, 31.4%; bacterial vaginosis, 2.3%; serologic syphilis, 4.6%; and
      genital ulcers on clinical examination, 10.6%. The best performance of algorithms
      were reached when using a combination of clinical signs and a search for gram
      negative diplococci on cervical smears (sensitivity, 64.4%; specificity, 80.0%).
      CONCLUSIONS: In the algorithms, examination of Gram-stained genital smears in
      female sex workers without clinical signs of cervicitis improved sensitivity
      without altering specificity for the diagnosis of cervical infection.

PMID- 10949432
TI  - The effect of treating sexually transmitted diseases on the transmission of HIV
      in dually infected persons: a clinic-based estimate. Ad Hoc STD/HIV Transmission
      Group.
AB  - BACKGROUND: The effect of sexually transmitted disease (STD) treatment on HIV
      transmission is a topic of considerable current interest and controversy. GOAL:
      To assess the potential effect of STD treatment on HIV transmission in persons
      who are dually infected with STD and HIV. STUDY DESIGN: Using data from eight STD
      clinic sites in the United States, the authors estimate the actual achievable
      reduction in HIV transmission by multiplying the prevented fraction associated
      with treatment of STDs (set at an average of 0.8) by the maximum potential
      reduction in HIV transmission achieved by treating STDs (using an average
      relative risk of 3.0 for increased HIV transmission in the presence of STDs).
      Subgroup analysis assessed infection proportions for genital ulcer disease,
      nonulcerative STDs, and any STD by sex, ethnicity, age, and sexual orientation.
      RESULTS: The maximum achievable reduction in HIV transmission from dually
      infected persons to their partners is approximately 33%. The actual achievable
      reduction is approximately 27% (range, 10.0-38.1%) at the eight clinic sites. If
      each of the 4,516 dually infected persons in this cohort experienced a single
      sexual exposure with an uninfected person, 28 HIV infections would occur in the
      absence of STD treatment whereas 16 infections would occur with STD treatment.
      CONCLUSIONS: The estimate of a 27% reduction provides a qualitative assessment of
      the potential impact of STD treatment on HIV transmission in the absence of any
      other behavioral intervention. Identification of dually infected persons in STD
      clinics is an important mechanism for targeting interventions to a social milieu
      with high risk for HIV infection and other STDs.

PMID- 10949433
TI  - Pattern of sexually transmitted diseases and risk factors among women attending
      an STD referral clinic in Nairobi, Kenya.
AB  - BACKGROUND: In Kenya, sexually transmitted disease (STD) clinics care for large
      numbers of patients with STD-related signs and symptoms. Yet, the etiologic
      fraction of the different STD pathogens remains to be determined, particularly in
      women. GOAL: The aim of the study was to determine the prevalence of STDs and of
      cervical dysplasia and their risk markers among women attending the STD clinic in
      Nairobi. STUDY DESIGN: A cross-section of women were interviewed and examined;
      samples were taken. RESULTS: The mean age of 520 women was 26 years, 54% had a
      stable relationship, 38% were pregnant, 47% had ever used condoms (1% as a method
      of contraception), 11% reported multiple partners in the previous 3 months, and
      32% had a history of STDs. The prevalence of STDs was 29% for HIV type 1, 35% for
      candidiasis, 25% for trichomoniasis, 16% for bacterial vaginosis, 6% for
      gonorrhea, 4% for chlamydia, 6% for a positive syphilis serology, 6% for genital
      warts, 12% for genital ulcers, and 13% for cervical dysplasia. Factors related to
      sexual behavior, especially the number of sex partners, were associated with
      several STDs. Gonorrhea, bacterial vaginosis, cervical dysplasia, and genital
      warts or ulcers were independently associated with HIV infection. Partners of
      circumcised men had less-prevalent HIV infection. CONCLUSION: Most women reported
      low-risk sexual behavior and were likely to be infected by their regular partner.
      HIV and STD prevention campaigns will not have a significant impact if the
      transmission between partners is not addressed.

PMID- 10949434
TI  - Surgical resection of jugulare foramen tumors by juxtacondylar approach without
      facial nerve transposition.
AB  - PRESENTATION: Jugulare foramen tumors (JFT) remain a difficult challenge
      especially in the forms extending extradurally and invading the petrous bone. In
      the standard technique, facial nerve function is placed at risks because of its
      transposition. We report on 31 extradural (N = 11) or intra-extra dural (N = 20)
      JFT resected surgically using the juxtacondylar approach alone or in combination
      with the infratemporal approach and without facial nerve transposition. RESULTS:
      The juxtacondylar approach permits the opening of the JF on its posteroinferior
      aspect and thus reduces the extent of petrous bone drilling. In tumors strictly
      located in the JF (N = 11), no petrous bone drilling is necessary and the facial
      nerve is never exposed. In tumors extending into the petrous bone (N = 20), the
      facial nerve was never transposed and moreover was kept in its bony canal in 15
      cases. In only 5 cases, was the fallopian canal opened as the tumor was invading
      its bony wall. Similarly hearing function, when pre-operatively intact was always
      preserved and a better preservation of the lower cranial nerves could be
      achieved. Whatever the tumoral extent along the petrosal carotid artery, a
      radical resection could be realized in 30 cases. CONCLUSION: Therefore, we
      consider the juxtacondylar approach a useful adjunct to increase the
      possibilities of resection of JFT; it allows a better preservation of the
      neurovascular structures, especially the facial nerve which is kept in place and
      moreover kept in its bony canal when it is not invaded by the tumor.

PMID- 10949435
TI  - Defining the role of stereotactic radiosurgery versus microsurgery in the
      treatment of single brain metastases.
AB  - Stereotactic radiosurgery (RS) and surgery have proved to be effective treatment
      modalities for brain metastasis. We followed 133 patients whose treatment for
      intracranial disease was either RS or a single surgical resection at the
      University of Vienna from August 1992 through October 1996. All patients who
      received additional Whole Brain Radiotherapy were included. This was a
      retrospective, case-control study comparing these treatment modalities. Sixty
      seven patients were treated by RS and 66 patients were treated by microsurgery.
      The median size of the treated lesions for RS patients was 7800 mm3, and 12500
      mm3 for microsurgery patients, respectively. The median dose delivered to the
      tumour margin for RS patients was 17 gray. The median survival for patients after
      RS was 12 months, and 9 months for patients after microsurgery. This difference
      was not statistically significant (p = 0.19). Comparison of local tumour control,
      defined as absence of regrowth of a treated lesion, showed that tumours following
      RS had a preferred local control rate (p < 0.05). Univariate and multivariate
      analysis showed that this fact was due to a greater response rate of
      "radioresistant" metastasis to RS (p < 0.005). Postradiosurgical complications
      included the onset of peritumoural oedema (n = 5) and radiation necrosis (n = 1).
      Two patients after microsurgery experienced local wound infection. One
      postoperative death occurred due to pulmonary embolism in this group. On the
      basis of our data we conclude that RS and microsurgery combined with Whole Brain
      Radiotherapy are comparable modalities in treating single brain metastasis.
      Concerning morbidity and local tumour control, in particular in cases of
      "radioresistant" primary tumours, RS is superior. Therefore we advocate RS except
      for cases of large tumours (> 3 cm in maximum diameter) and for those with mass
      effect.

PMID- 10949436
TI  - Evaluation of dissemination studies with FDG whole-body positron emission
      tomography in patients with suspected metastatic tumours of brain and spine.
AB  - BACKGROUND: In the preoperative diagnosis of malignant brain tumours there is
      often uncertainty regarding their metastatic or primary nature, requiring
      dissemination studies. Currently FDG-wbPET is being used for the efficient
      detection of systemic tumours. It therefore may become a substitute for the
      conventional dissemination studies if it allows an earlier diagnosis. METHOD: In
      this descriptive and preliminary study a population of 14 patients with suspected
      or proven metastatic lesions, [18F]-fluoro-2-deoxy-D-glucose whole body positron
      emission tomography (FDG-wbPET) was conducted and verified by additional
      conventional dissemination studies. FINDINGS AND THEIR INTERPRETATION: The entire
      series of dissemination studies required an average of 30 days with a range of 4
      73 days. The FDG-wbPET was corroborated by the other dissemination studies in 10
      of the 14 patients. In 7 of these 10 patients both PET and dissemination studies
      showed systemic abnormal findings, but in one case the presence of high pulmonary
      activity on the FDG-wbPET and the abnormal findings on the chest X-rays proved to
      be Aspergillus infection at autopsy. In the other 2 cases the negative PET
      findings corresponded to the absence of systemic dissemination. In 5 cases there
      was disagreement of the results of the FDG-wbPET with other evidence, among which
      there were 2 cases of glioblastoma in which systemic metastases were most
      unlikely, and the foci of activity on the FDG-wbPET had to be considered as false
      positives. In the remaining 3 cases the systemic presence of high activity on the
      FDG-wbPET indicated the systemic presence of tumour, whereas the other
      dissemination studies disclosed no tumour. CONCLUSION: The results warrant the
      use of FDG-wbPET as a screening method for the search of metastases, allowing
      other studies to be focussed on the lesion. But from the cost/benefit point of
      view this would make the method less suitable as a substitute for dissemination
      studies in general, although it may speed up the diagnostic process.

PMID- 10949438
TI  - Stereotactic radiosurgery for hemangioblastomas of the brain.
AB  - OBJECTIVE: To assess the effectiveness of stereotactic radiosurgery in achieving
      tumor control and improving survival in patients with hemangioblastoma, we
      evaluated results from patients who were managed at the University of Pittsburgh
      and the Mayo Clinic. PATIENTS AND METHODS: Twenty-seven patients with 29
      hemangioblastomas had stereotactic radiosurgery over a 10 year interval. The mean
      patient age was 32 years (range, 14-75 years). The tumor volumes varied from 0.36
      to 27 ml (mean, 3.2 ml), and the mean tumor margin dose was 16 Gy (range, 11.7
      20). Clinical and neuroimaging follow-up was obtained for all patients between
      0.5 and 9 years (mean, 4 years) after radiosurgery. RESULTS: At this assessment,
      21 patients (79%) were alive and six (21%) had died. The median survival after
      radiosurgery was 6.5 years (actuarial 5 year survival = 75.1 +/- 11.5%). The
      median survival from the initial diagnosis was 15 years. Twenty two of 29
      evaluable tumors were controlled locally. The two-year actuarial control rate was
      84.5 +/- 7.1% and at five years, 75.2 +/- 8.9%. Multivariate testing of factors
      affecting good outcome indicated that smaller tumor volume and higher
      radiosurgical dose (> 18 Gy) were significant. CONCLUSION: For small to moderate
      size hemangioblastomas, multiple or recurrent tumors, and for patients who are
      not surgical candidates, radiosurgery is a safe and effective option to control
      disease and improve survival.

PMID- 10949437
TI  - Efficacy of post operative adjuvant therapy with human interferon beta, MCNU and
      radiation (IMR) for malignant glioma: comparison among three protocols.
AB  - In order to develop ultimate adjuvant therapy for malignant gliomas, we analysed
      77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48
      glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human
      interferon-beta (HuIFN-beta), MCNU and radiation). In protocol 1 (n = 45: AA =
      13, GM = 32), 1 x 10(6) IU of HuIFN-beta was administrated intravenously once a
      day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w.
      intravenously and from day 3, radiation was started in five weekly fractions of 2
      Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n = 19: AA = 11, GM = 8) was
      comparable with protocol 1 except HuIFN-beta was administrated twice a day at a
      dose of 1 x 10(6) IU each. Protocol 3 (n = 13: AA = 5, GM = 8) differed from
      protocol 2 only in a high dose-hyperfractionated radiation which was given twice
      a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects
      were evaluated by survival and response rate determined by decrease of tumor
      size. Significant improvement was obtained in patients with AAs by protocol 2 and
      3. Response rates of patients with AAs and GMs were 46.2% and 50% in protocol 1,
      63.6% and 50% in protocol 2, and 80% and 50% in protocol 3, respectively. One and
      two year survival rates in AAs were 46.4% and 34.8% in protocol 1, both 75% in
      protocol 2, and both 100% in protocol 3. Survival rates in GMs were not different
      among them. Except of radiation necrosis, which was observed in 38.5% of the
      patients under protocol 3, there was no significant difference in the adverse
      effects among the three protocols. In the present study, the efficacy of IMR
      therapy for patients with malignant gliomas, especially for AAs, was cofirmed. We
      conclude that twice a day administrations of HuIFN-beta in combination with a
      high dose-hyperfractionated radiation provide increased efficacy in IMR therapy.

PMID- 10949439
TI  - Gamma knife radiosurgery of skull base meningiomas.
AB  - BACKGROUND: The standard surgical treatment of meningiomas is total resection of
      the tumour. The complete removal of skull base meningiomas can be difficult
      because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an
      effective therapy, either for adjuvant treatment in case of subtotal or partial
      tumour resection, or as solitary treatment in asymptomatic meningiomas. METHOD:
      Between September 1992 and October 1995. SRS using the Leksell Gamma Knife was
      performed on 46 patients (f:m 35:15), ranging in age from 35 to 81 years, with
      skull base meningiomas at the Neurosurgical Department of the University of
      Vienna. According to the indication of gamma knife radiosurgery (GKRS) the
      patients (n = 46) were divided into two subgroups. Group I (combined procedure:
      subtotal resection followed by GKRS as a planned procedure or because of a
      recurrent meningioma), group II (GKRS as the primary treatment). Histological
      examination of tumour tissue was available for 31 patients (67%) after surgery
      covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes. FINDINGS: The
      overall tumour control rate after a mean follow-up period of 48 months (ranging
      from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas).
      Group I displayed a 96.7% tumour control rate, followed by group II with 93.3%
      respectively. Neurological follow-up showed an improvement in 33% stable clinical
      course in 58%) and a persistent deterioration of clinical symptoms in 9%.
      Remarkable neurological improvement after GKRS was observed in group II (47%),
      whereas in group I (26%) the amelioration of symptoms was less pronounced.
      INTERPRETATION: GKRS in meningiomas is a safe and effective treatment. A good
      tumour control and low morbidity rate was achieved in both groups (I, II) of our
      series, either as a primary or adjunctive therapeutic approach. The planned
      combination of microsurgery and GKRS extends the therapeutic spectrum in the
      treatment of meningiomas. Reduction of tumour volume, increasing the distance to
      the optical pathways and the knowledge of the actual growing tendency by
      histological evaluation of the tumour minimises the risk of morbidity and local
      regrowth. Small and sharply demarcated tumours are in general ideal candidates
      for single high dose-GKRS, even after failed surgery and radiation therapy, and
      in special cases also in larger tumour sizes with an adapted/reduced margin dose.

PMID- 10949440
TI  - Usefulness of gallium-67 scintigraphy in neurohypophyseal germinoma.
AB  - The application of gallium-67 (67Ga) citrate has not been reported for the
      detection of an intracranial germinoma. The purpose of this report is to further
      evaluate the effectiveness of 67Ga scintigraphy in neurohypophyseal germinomas.
      67Ga studies in five male patients with histologically verified intracranial pure
      germinomas were evaluated. Two germinomas were located in the neurohypophysis,
      two in the pineal region, and one in both the neurohypophysis and pineal region.
      The control group included 36 patients with histologically verified pituitary
      macro-adenomas. 67Ga study at the time of original diagnosis showed an abnormal
      accumulation in two neurohypophyseal germinomas, and negative accumulation in the
      other germinomas. In the two patients with neurohypophyseal germinomas, 67Ga
      study showed an abnormal accumulation in the intracranial tumour region in
      accordance with magnetic resonance (MR) findings. After postoperative irradiation
      or chemoradiotherapy, MR imaging and 67Ga studies revealed the complete
      disappearance of this tumour and no metastatic spread. In one of these two
      patients, a whole-body 67Ga study demonstrated multiple bone metastases one year
      later, and the reduction of these metastatic regions after chemotherapy. 67Ga
      study disclosed negative accumulation in all 36 pituitary macroadenomas. Although
      67Ga uptake by neurohypophyseal germinomas may not be specific for this
      condition, this approach may provide some clues for diagnosing patients with
      neurohypophyseal germinomas.

PMID- 10949441
TI  - Occipital bone graft for atlantoaxial fusion.
AB  - BACKGROUND: Instability of the atlantoaxial segment is frequently encountered in
      neurosurgical practice. Numerous fusion techniques have been employed at this
      level. Most commonly, arthrodesis is achieved through bone and wire techniques.
      We have employed the use of suboccipital bone in lieu of iliac crest autograft in
      order to avoid the significant morbidity associated with iliac crest graft
      harvest. METHODS: Twenty one patients suffering instability from various
      etiologies underwent C1-C2 fusion at our institution using occipital bone graft
      and wire fixation. A small craniectomy was performed near the foramen magnum, and
      the bone graft was notched and secured in place using wire fixation. Patients
      were placed in a Philadelphia or Aspen collar for 6-12 weeks postoperatively, and
      flexion/extension plain film of the cervical spine were used to evaluate fusion.
      RESULTS: Long term follow up was available on all patients (mean 32 months, range
      12-48 months). Fusion was achieved in 81% of patients within 12 weeks.
      Specifically, 71% (5/7) of rheumatoid patients were successfully fused. All
      patients with traumatic C1-C2 instability were fused. No complications were
      associated with the harvest of the occipital bone. CONCLUSION: The results of
      fusion via this technique are comparable to other reported series of C1-C2
      fusion. Additionally, the complications associated with iliac crest graft harvest
      were avoided by the use of occipital bone graft. Occipital bone appears to be a
      suitable bone graft substance for fusion of the C1-C2 level.

PMID- 10949442
TI  - Lumbar intervertebral disc herniation following experimental intradiscal pressure
      increase.
AB  - An experimental biomechanical model of overload and rupture of the annulus
      fibrosus (AF) and lumbar disc herniation was achieved by increasing intradiscal
      pressure while keeping disc height constant in 69 motion segments at the L4-L5
      level excised from cadaveric spines. The experiments were made on 53 specimens in
      neutral posture and on 16 specimens in flexion posture. The values found for the
      rupture intradiscal pressure (RIP) ranged from 750 to 1300 kPa for neutral
      posture and the maximum RIP in anterior flexion was 1177 kPa. The degree of disc
      degeneration was assessed by vertebral transcorporeal discography (previous to
      experiment) and by sectioning the intervertebral disc after the experiment. The
      herniated lumbar intervertebral disc model by intradiscal pressure increase makes
      possible these assertions: * The correlation between the degree of AF
      degeneration and the RIP is significant: the maximum RIP corresponds to a non
      degenerated AF and the less RIP can tear only a degenerated AF; so disc
      herniation only occurs to discs with torn AF. * AF breaking is more often
      paramedian, left or right. The place of AF breaking was paramedian in 70.3%
      cases, median in 9.45% cases and posterolateral in 20.25% cases.

PMID- 10949444
TI  - Percutaneous controlled radiofrequency rhizotomy in the management of patients
      with trigeminal neuralgia due to multiple sclerosis.
AB  - Between the years 1974 and 1999, 1,672 patients with medically intractable
      trigeminal neuralgia (TN) were treated by percutaneous controlled radiofrequency
      (RF) rhizotomy by the senior author and co-workers at the Department of
      Neurosurgery, Ankara University School of Medicine. Sixteen hundred cases (95.7%)
      were found to have idiopathic TN, while 72 cases (4.3%) were classified as
      symptomatic. In the latter group, TN was found to be caused by multiple sclerosis
      (MS) in 17 cases (23.6%), one of whom had bilateral TN. All patients having TN
      with MS (17 cases) underwent percutaneous controlled radiofrequency rhizotomy (25
      procedures) as the procedure of choice. The MS patients were followed for an
      average of 60 months (range: 6-141 months). Complete pain relief was achieved
      with a single procedure in 12 of the 17 MS cases (70.6%). Early (less than 2
      weeks) pain recurrence was seen in two patients (11.8%), while the overall
      recurrence rate was 29.4%. A second procedure was required to control TN in three
      cases (17.6%), a third in one (5.9%), and twice for each side for the case with
      bilateral TN (5.9%). Pain was completely relieved in 14 cases (82.4%) with single
      or multiple RF rhizotomies. In three cases (17.6%), partial pain control was
      achieved with RF rhizotomy, and the patients continued to receive adjunctive
      medical therapy. No complications were observed. All 17 patients (100%) were
      classified to have done well with RF rhizotomy. Satisfactory results and good
      long-term pain control were obtained in patients having TN due to MS with
      percutaneous controlled RF rhizotomy. The authors propose that RF rhizotomy may
      be a safe and effective procedure in the neurosurgical armamentarium for the
      treatment of patients having TN due to MS.

PMID- 10949443
TI  - Introduction of GDC embolization in the clinical practice as treatment synergical
      to surgery: impact on overall outcome of patients with subarachnoid hemorrhage.
AB  - The GDC endovascular approach represent an effective alternative to surgery for
      treatment of intracranial aneurysms. Anyway no data are available about the
      impact of endovascular embolization with GDC on overall outcome of patients with
      subarachnoid hemorrhage. We analyse retrospectively a series of 234 patients
      admitted for ruptured intracranial aneurysm. Results were then compared with
      results of three surgical series from the literature. The 95.7% of patients
      underwent aneurysm treatment; 56.4% of patients were classified as good recovery,
      12.8% presented moderate disability, 10.3% were severely disabled, 3% were in
      persistent vegetative state and 17.5% were dead. Patients older than 60 years
      accounted for 37% of all cases and good outcome in this group accounted for
      54.7%. Good results were obtained in 90.1%, 61.7% and 22.8% of patients with Hunt
      Hess grade I-II, III and IV-V respectively. Finally good outcome was observed in
      82.8% of patients with aneurysms of the posterior circulation. Introduction of
      GDC embolization in clinical practice contributed to the extension of indication
      for aneurysm treatment leading to a reduction of overall mortality. GDC
      utilisation does not affect the overall percentage of patients with good outcome
      reflecting an increase of severely disabled patients. Endovascular treatment
      seems an effective theraputic choice in selected grade I-II patients. Results in
      grade III patients suggest that surgery may be advantageous because of washing
      and decompression of the basal cisterns while results in grade IV and V patients
      are unsatisfactory. GDC embolization clearly improves the prognosis of patients
      with posterior circulation aneurysms and probably is an advantageous theraputic
      choice in elderly patients.

PMID- 10949445
TI  - Endoscopic transthoracic sympathicotomy affects the autonomic modulation of heart
      rate in patients with palmar hyperhidrosis.
AB  - BACKGROUND: Palmar hyperhidrosis has been associated with an increased activity
      of the sympathetic nervous system. The objective of this study was to assess the
      immediate and long-term effects of endoscopic transthoracic sympathicotomy on the
      autonomic modulation of the heart rate in patients with palmar hyperhidrosis.
      METHODS: Power spectrum analysis of heart rate variability in the lying position
      and after passive tilt to the upright position was performed in thirteen patients
      the day before and after sympathicotomy. A follow-up recording was performed in
      ten patients approximately six months later. Recordings from 26 healthy subjects
      were used as a reference group. FINDINGS: The patients had a tendency to higher
      power of the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF; above 0.15
      Hz) components than controls in the upright position. After sympathicotomy LF
      power was reduced, but HF power was unchanged. At follow-up LF power remained at
      a lower level, but now HF power was reduced. INTERPRETATION: Patients with palmar
      hyperhidrosis have a sympathetic overactivity but also a compensatory high
      parasympathetic activity. Sympathicotomy results in an initial sympathovagal
      imbalance with a parasympathetic predominance, which is restored on a long-term
      basis.

PMID- 10949446
TI  - Spontaneous acute subdural hematomas. A clinical comparison with traumatic acute
      subdural hematomas.
AB  - A comparison was made between factors influencing survival in patients operated
      on for acute spontaneous subdural hematomas (ASSH) and other groups of patients
      operated for acute, post-traumatic, subdural hematoma reported in the literature.
      The data of 17 patients operated on for ASSH were collected. Four variables:
      early surgical treatment, high Glasgow Coma Scale score on admission, pupillary
      reactivity and age were statistically analyzed. The most significant factors for
      good outcome, in order of importance, were early surgical treatment, a high
      Glasgow Come Scale score on admission, good pupillary reactivity and younger age.
      The prognostic factors in non-traumatic and traumatic acute subdural hematomas
      were found to be identical.

PMID- 10949447
TI  - Spinal papillary meningioma: a case report and review of the literature.
AB  - A rare case of a spinal papillary meningioma in a 19-year-old adolescent is
      described. Six months after radical resection the patient showed dissemination
      along the cerebrospinal pathway. Papillary meningiomas are rare tumours with a
      relatively high incidence in childhood. Most papillary meningiomas reported in
      the literature are considered as aggressive variants of meningioma with often
      local recurrence, dissemination in the CSF and metastases to remote sites. This
      case supports that, although the histogenesis remains unexplained, papillary
      meningiomas deserve recognition on the basis of their high morbidity and
      mortality.

PMID- 10949448
TI  - Symptomatic delayed arterial spasm following non-aneurysmal perimesencephalic
      subarachnoid hemorrhage: a case report and review of the literature.

PMID- 10949449
TI  - Craniospinal pachymeningitis.

PMID- 10949451
TI  - Importance of magnetic resonance imaging in the conservative management of
      posterior fossa epidural haematomas: case illustration.

PMID- 10949450
TI  - Enterogenous cyst of the cisterna magna.

PMID- 10949452
TI  - Intraneural metastasis in a peripheral nerve.

PMID- 10949453
TI  - Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large
      B-cell lymphoma.
AB  - The morphologic spectrum of large B-cell lymphoma is broad. Several unusual
      variants have been described such as lymphoma with myxoid stroma, sclerosing B
      cell lymphoma, signet ring-cell lymphoma, and multilobated B-cell lymphoma among
      others. We report on five cases of cutaneous large B-cell lymphoma in which the
      neoplastic cells were spindle-shaped. In two cases, the clinical features
      fulfilled those of a primary cutaneous lymphoma; in the three other cases, the
      lymphoma most likely arose primarily in the skin, but incomplete clinical workups
      precluded definite categorization. The patients ranged in age from 30 to 89 years
      and presented with solitary lesions on the trunk or head. Histopathologic
      examination revealed nodular or dense diffuse infiltrates involving the entire
      dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles
      between the spindled cells were present in one case. Cytomorphologic analysis
      showed the presence of round or oval medium-sized and large-sized lymphocytes
      with features of centrocytes and centroblasts in some foci, with others dominated
      by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin
      and scant cytoplasm. Immunohistologic analysis revealed that both round or oval
      and spindled cells were positive for CD20 in all cases; in all cases tested,
      these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43,
      CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and
      cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the
      rearrangement of the J(H) gene by polymerase chain reaction performed in one case
      showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a
      distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise
      primarily in the skin in some cases. Recognition of this variant is necessary to
      avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.

PMID- 10949454
TI  - Solitary keratoacanthoma: a self-healing proliferation that frequently becomes
      malignant.
AB  - To discuss the relation between solitary keratoacanthoma (KA) and crateriform
      squamous cell carcinoma (cSCC), the clinical and histologic features of cutaneous
      crateriform squamous cell proliferations were studied. Two hundred twenty cases
      of wholly excised crateriform squamous cell proliferations were studied both
      clinically (age, sex, location, and duration) and histologically (hematoxylin
      eosin-stained sections). For comparison, we studied 100 consecutive cases of
      wholly excised noncrateriform squamous cell carcinoma (ncSCC). One hundred forty
      four of the 220 cases of crateriform squamous cell proliferations were
      histologically classified as KA. In 47 other cases, a relatively large area of
      the KA showed frank histologic and cytologic malignant transformation (mKA); this
      event could happen during every stage of the KA. Twenty-nine lesions were cSCCs
      without remnants of KA. The patients in the KA group were significantly younger
      (p = 0.000) than those in the other three groups. The ages of the patients in
      these three groups were not significantly different (p = 1.0). More KAs (16%)
      were located in areas that are not usually exposed to the sun than was the case
      with the other groups of neoplasms considered (2%, 3%, and 3%, respectively), and
      this difference was statistically significant (p = 0.001). Regarding the duration
      of the lesion, only the differences between KA and cSCC, KA and ncSCC, and mKA
      and ncSCC were statistically significant. Not every cutaneous crateriform
      squamous cell proliferation is a KA; in KA, the crater must be multilocular, the
      "lips" must be perforated, and the cornified contents do not usually project out
      of the "mouth." At least a quarter of KAs undergo malignant transformation, which
      occurs more frequently in older patients and photoexposed areas. This
      transformation is a focal event and may happen at any stage of KA development.
      Consequently, a suspected KA must be wholly excised and studied in serial
      paraffin blocks so as to disclose any focus of malignant transformation.

PMID- 10949455
TI  - Merked cells and sclerosing epithelial neoplasms.
AB  - Merkel cells are normal constituents of the basal layer of the epidermis and the
      follicular epithelium. They have been identified in benign neoplasms with
      follicular germinative differentiation but seem to be absent in basal cell
      carcinomas (BCCs). Because sclerosing epithelial neoplasms are often sampled by
      small biopsies, any method that enables distinction among them would be welcome.
      We used immunohistochemical staining for cytokeratin 20 to assess the presence of
      Merkel cells in 14 cases of desmoplastic trichoepithelioma (DTE), 12 specimens of
      syringoma, 11 samples of morpheiform BCC, and 8 specimens of microcystic adnexal
      carcinoma (MAC). Merkel cells were found in association with all 14 specimens of
      DTE and in 1 of 11 cases of morpheiform BCC (p < 0.005) but in none of the
      specimens of syringoma or MAC. Our study supports previous findings that Merkel
      cells are seen in association with cutaneous neoplasms that are benign and of a
      follicular germinative origin. Although MAC may differentiate along follicular
      sebaceous-apocrine lines, the absence of Merkel cells within it is consistent
      with its malignancy. The identification of Merkel cells in a sclerosing
      epithelial neoplasm of the skin points to DTE as the most likely diagnosis.

PMID- 10949456
TI  - Lymphohistiocytic and granulomatous phlebitis in penile lichen sclerosus.
AB  - Lichen sclerosus (LS) is a chronic inflammatory disease of unknown etiology that
      may affect the genital and/or extragenital skin of individuals of either sex at
      all ages. In boys, the prepuce is the most common site of involvement. The
      diagnostic criteria of LS include the presence of inflammatory infiltrates mainly
      composed of T lymphocytes. We report on two cases of LS of the prepuce because of
      the unusual feature of lymphocytic (CD45RO+ and CD20+), histiocytic (CD68+), and
      granulomatous phlebitis. This lesion was not present in a group of another 18
      cases of childhood penile LS. We have not been able to find any references
      describing and illustrating inflammatory involvement of the dermal vein walls in
      LS. Unlike the data reported in the literature, the dermal inflammatory
      infiltrates of these two cases showed a similar proportion of B and T lymphocytes
      in addition to frequent CD68+ histiocytes.

PMID- 10949457
TI  - PCR-heteroduplex analysis of T-cell receptor gamma gene rearrangement in paraffin
      embedded skin biopsies.
AB  - We developed a rapid, simple, and sensitive method for the detection of T-cell
      receptor-gamma (TCRgamma) gene rearrangements in paraffin-embedded skin biopsies.
      Available techniques often require either fresh tissue, several primer pairs,
      nested amplifications, or specialized electrophoresis steps such as denaturing
      gradient gel electrophoresis. Our method is based on heteroduplex analysis of
      polymerase chain reaction (PCR) products of the TCRgamma in a nondenaturing
      modified polyacrylamide gel using a single pair of primers and is adapted for
      paraffin-embedded tissue. When tested against Southern blot analysis, the PCR
      results correlated in 8 of 9 cases. Six mature cutaneous B-cell lymphomas and 29
      inflammatory skin disorders all resulted in a polyclonal amplification pattern.
      When analyzing 3-mm or 4-mm punch biopsies of 51 cases of cutaneous T-cell
      lymphoma, 37 (72.5%) showed a clonal rearrangement with this technique. For 7
      cases of patch stage mycosis fungoides, frozen tissue and formalin-fixed and
      paraffin-embedded tissue was available, and in 5 of 7 cases (71%), the results in
      frozen and paraffin-embedded tissue were concordant. One case showed a clonal
      pattern in frozen tissue but not in paraffin-embedded tissue, and one case was
      polyclonal in frozen tissue but monoclonal in paraffin-embedded tissue. Using
      serial dilutions of DNA from a T-cell ALL in a polyclonal background (tonsil), we
      established a sensitivity of 0.5%. Heteroduplex PCR of the TCRgamma is a rapid,
      sensitive, and inexpensive screening procedure as well as a useful adjunct to
      histologic analysis and immunophenotyping of cutaneous T-cell proliferations.

PMID- 10949458
TI  - Kikuchi-Fujimoto necrotizing lymphadenitis associated with cutaneous lupus
      erythematosus: a case report.
AB  - Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a rare
      entity, and even more rarely, it is associated with other diseases. In a few
      cases, the condition is associated with cutaneous lupus erythematosus (CLE).
      Histiocytic necrotizing lymphadenitis predominantly affects young women, who
      present with solitary or multiple cervical lymphadenopathy accompanied by
      symptoms such as fever, weight loss, sweating, or, in exceptional cases,
      hepatosplenomegaly. Laboratory examinations show normal or nonspecific results.
      The disease is of unknown origin, although a viral origin has been suggested,
      with the suspected agents including Epstein-Barr virus, herpesvirus type 6, and
      cytomegalovirus (CMV). Although the first and most of the more recent cases have
      been reported in Oriental patients, the disease has a wide geographic
      distribution. The clinical evolution is favorable, with spontaneous remission in
      less than 4 months in almost all cases. We present a case of a 37-year-old woman
      from Peru who presented with cervical adenopathies on two occasions. Biopsy of a
      lymph node revealed a histopathologic picture compatible with Kikuchi-Fujimoto
      histiocytic necrotizing lymphadenitis. The adenopathy disappeared in a few
      months. A year later, she presented with a maculopapular rash in the nasal and
      malar regions. The results of the skin biopsy and immunofluorescence examination
      were compatible with chronic CLE. The results of the serology testing for CMV
      were positive. Treatment with chloroquine was initiated, with almost complete
      recovery by 5 months. No manifestations of systemic lupus erythematosus have
      occurred since. The epidemiologic, clinical, and anatomopathologic aspects as
      well as the differential diagnosis of this entity are reviewed.

PMID- 10949459
TI  - Angioendotheliomatosis in a woman with rheumatoid arthritis.
AB  - Reactive angioendotheliomatosis (RA) is a rare self-limited skin condition
      characterized histopathologically by a proliferation of endothelial cells within
      vascular lumina, usually as a result of different stimuli such as systemic
      infections, cryoproteinemias, monoclonal gammopathies, allergic conditions,
      severe peripheral vascular atherosclerotic disease, and iatrogenic arteriovenous
      fistulas. We report on a 67-year-old woman with a 20-year history of seropositive
      rheumatoid arthritis who presented with violaceous swelling of her left forearm.
      A skin biopsy revealed the histopathologic finding of RA with focal glomeruloid
      features and deposition of periodic acid-Schiff-positive material. In this
      systemic disorder, cutaneous manifestations may occur secondary to an immune
      complex-mediated vasculitic mechanism.

PMID- 10949460
TI  - Penile hybrid verrucous-squamous carcinoma associated with a superficial inguinal
      lymph node metastasis.
AB  - A 62-year-old Japanese man who presented with penile carcinoma is reported. The
      initial exophytic neoplasm excised from the coronal sulcus and prepuce on the
      abdominal side of the penis was diagnosed histologically as verrucous carcinoma.
      Twenty-six months after the primary operation, an epithelial neoplasm recurred
      within the scar of the primary operation. The neoplasm histologically showed
      verrucous carcinoma and multiple invasive foci of conventional squamous cell
      carcinoma in the advancing edge of the tumor, as such representing a hybrid
      verrucous-squamous carcinoma. A lymph node metastasis in the left superficial
      inguinal lymph node occurred 4 months after the second operation. A total
      bilateral inguinal lymphadenectomy was performed and revealed no other lymph node
      metastases. The patient is alive without local recurrence or evidence of
      metastases in pelvic lymph nodes or visceral organs 2 years after the resection
      of the hybrid verrucous-squamous carcinoma. The initial verrucous carcinoma,
      recurrent hybrid verrucous-squamous carcinoma, and metastatic lymph node were
      negative for human papillomavirus DNA type 6, 11, 16, 18, and 33 sequences by dot
      blot hybridization of polymerase chain reaction products. The characteristics of
      hybrid verrucous-squamous carcinoma and importance of lymph node metastasis in
      penile carcinoma are discussed.

PMID- 10949461
TI  - Cutaneous myoepithelioma?

PMID- 10949462
TI  - Lymphocytes + nerves = ?

PMID- 10949463
TI  - Primary or primarily?

PMID- 10949464
TI  - Aggressive angiomyxoma with multinucleated giant cells: a lesion mimicking
      liposarcoma.

PMID- 10949465
TI  - Multiple glomangiomyoma versus glomangioma: conceptual and ultrastructural
      observations.

PMID- 10949466
TI  - Increased p53 staining in non-sun-exposed epidermis overlying Kaposi sarcoma.

PMID- 10949467
TI  - Physical evidence of two wall effects in liquid chromatography.
AB  - Using optical on-column visualization for the study of the migration of sample
      bands, the radial variations of the local migration rate were studied in the
      region near the column wall. Photographs of small sample bands migrating along
      the column at various radial locations were obtained. On-column chromatograms
      extracted from these photographs showed evidence of two wall effects. The first
      of these effects was present only within the immediate vicinity of the wall. It
      is a direct result of the inability of the packing material to form a close
      packed configuration against the rigid column wall surface. The second wall
      effect causes a systematic variation of the migration rate of the sample band in
      the region of the wall, this rate increasing from the wall to the central region
      of the column. The corresponding images portrayed the classical "wall effect"
      that chromatographers have long discussed. They also show that this effect
      extends further into the column than anticipated. As to what are the relative
      contributions to the results of our observations of the wall effect and of a frit
      effect discussed in previous publications, this could not be ascertained.

PMID- 10949468
TI  - Antibody immobilization to high-performance liquid chromatography supports.
      Characterization of maximum loading capacity for intact immunoglobulin G and Fab
      fragments.
AB  - This study examined various factors that affect the maximum amount of intact
      immunoglobulin G (IgG) or Fab fragments that can be covalently immobilized to
      silica and other HPLC-grade supports for use in immunoaffinity chromatography or
      immunoextractions. Factors that were considered included the amount of surface
      area available for immobilization, the pore size of the support, the type of
      immobilization method and the nature of the support matrix. The main factor in
      determining the extent of immobilization was found to be the relationship between
      the support's surface area and the ability of the IgG or Fab fragments to reach
      this surface. Access to the support surface was a function of the size of the
      protein being immobilized and the support porosity, with maximum immobilization
      being obtained with supports having pore sizes of approximately 300 A for intact
      IgG and 100 A for Fab fragments. Some differences in the maximum level of
      immobilization were noted between different coupling methods. Supports like Poros
      and Emphaze gave similar results to those seen with HPLC-grade silica when a
      comparison was made between materials with comparable pore sizes. Many of the
      trends observed in this work for IgG and Fab fragments should apply to other
      proteins that are to be immobilized to HPLC supports.

PMID- 10949469
TI  - Affinity screening by packed capillary high-performance liquid chromatography
      using molecular imprinted sorbents. I. Demonstration of feasibility.
AB  - Molecular imprint polymers (MIPs) are synthetic polymers capable of selectively
      binding a template molecule. In this work, the potential utility of MIP-based
      chromatographic sorbents for affinity screening of structurally similar compounds
      was investigated as alternatives to in vitro bioassays and biological targets
      bound to chromatographic supports. A group of structurally similar tricyclic
      antidepressant drugs and related compounds were used to simulate a combinatorial
      library. One of the antidepressants, nortriptyline (NOR), was selected as the
      template species. Using capillary HPLC columns packed with NOR-imprinted MIP
      particles, the simulated library was screened and the degree of selective
      interaction of each compound was determined. This correlated with each compound's
      affinity for the NOR binding site in the polymer. The results of the study
      revealed that library species which possess the major structural features of the
      template, specifically the ring structure and pendant secondary amine, were best
      "recognized" by the MIP, while the most structurally dissimilar compounds
      exhibited the least selective interaction. An investigation of the retention
      mechanism on these MIPs provided evidence that hydrogen bonding between the
      pendant amine group on the antidepressants and a methacrylic acid moiety on the
      polymer surface was critical in the molecular recognition process.

PMID- 10949470
TI  - Assessment of polycrystalline graphites as sorbents for solid-phase
      microextraction of nonionic surfactants.
AB  - Two polycrystalline graphites (pencil lead and glassy carbon) were used as
      sorbents for solid-phase microextraction of a nonionic alkylphenol ethoxylate
      surfactant (Triton X-100). Analyses were performed by reversed-phase HPLC
      fluorescence detection. The presence of the benzene ring in the congeners of
      Triton X-100 also allowed their direct detection at lambda(ex) = 230 nm and
      lambda(em) = 310 nm. Variables such as time of adsorption, time of desorption and
      concentration of surfactant in water were evaluated. The method limit of
      detection was found to be 0.5 microg/l for Triton X-100, with a linear dynamic
      range of 0.5-150 microg/l. Results were compared to those obtained using
      polymeric fibers such as PDMS/DVB and Carbowax/TPR. The chemical resistance and
      low cost of the polycrystalline graphites are advantageous over commercially
      available SPME fibers.

PMID- 10949471
TI  - High-speed recovery of germanium in a convection-aided mode using functional
      porous hollow-fiber membranes.
AB  - A porous hollow-fiber membrane capable of recovery of germanium from a liquid
      stream was prepared by radiation-induced graft polymerization of an epoxy-group
      containing vinyl monomer, glycidyl methacrylate, and subsequent functionalization
      with 2,2'-iminodiethanol, di-2-propanolamine, N-methylglucamine, and 3-amino-1,2
      propanediol. The functional group density was as high as 1.4 mol per kg of the
      resultant hollow fiber. The polymer chains containing functional groups
      surrounding the pores enabled a high-speed recovery of germanium during
      permeation of a germanium oxide (GeO2) solution through the pores of the hollow
      fiber. Because of a negligible diffusional mass-transfer resistance, germanium
      concentration changes with the effluent volume, i.e., breakthrough curves,
      overlapped irrespective of the residence time of the solution, which ranged from
      0.37 to 3.7 s across the hollow fiber. After repeated use of adsorption and
      elution, the adsorption capacity did not deteriorate.

PMID- 10949473
TI  - Influence of mobile phase composition and cross-linking density on the
      enantiomeric recognition properties of molecularly imprinted polymers.
AB  - A series of experiments were conducted to investigate elements which affect the
      enantiomeric recognition properties of molecularly imprinted polymers (MIPs) in
      the HPLC mode. Our results show that the recognition properties of MIPs are
      greatly influenced by the mobile phase used. For a polymer prepared in
      acetonitrile, a good enantiomeric separation was observed when acetonitrile-based
      mobile phase was used, when the mobile phase was changed to chloroform-based, no
      enantiomeric recognition was observed although the sample molecule was retarded.
      This indicates that the specific co-operative binding interactions between the
      functional groups at the imprinted polymer's recognition sites and the sample
      molecule were considerably disrupted and only non-specific interactions remained.
      When the mobile phase was changed back to acetonitrile-based, the recognition was
      regained. In contrast, for polymers prepared in chloroform, chloroform-based
      mobile phase gave much better separation than acetonitrile-based mobile phase.
      When other solvents were tested, significant solvent effects were generally
      observed. Based on these observations, the recognition properties of the
      methacrylic acid (MAA)-co-ethylene glycol dimethacrylate (EGDMA) polymers were
      reinvestigated, and the results show that by simply using an optimised mobile
      phase system, significantly improved recognition over previously reported results
      was observed. For a polymer made against Cbz-L-Trp, 100 microg of Cbz-D,L-Trp was
      separated with a separation factor (alpha) of 4.23 and a resolution (Rs) of 3.87,
      whereas in the previous report, 10 microg of Cbz-D,L-Trp was only separated with
      alpha = 1.67 and Rs = 0.1. It is generally realised that the imprinted polymer's
      recognition property is also very much influenced by the nature of the polymer
      network. It was shown that the recognition decreased with a decrease in the
      apparent degree of cross-linking (molar percentage of cross-linker in the
      polymerisation mixture). Nonetheless, our results show that in our optimised
      assay system a significant separation could still be obtained on a polymer which
      was only 22% cross-linked. We consider this to be of importance, since it may
      suggest a way of imprinting larger molecules because of the possibly improved
      mass transfer in low cross-linking density polymers. It was reported that when
      trifunctional cross-linkers [for example: trimethylolpropane trimethacrylate
      (TRIM)] were used as the cross-linker instead of EGDMA, considerably improved
      enantiomeric separation and resolving capability were observed. Our results show
      that the improved performance of the MAA-co-EGDMA MIPs is actually comparable to
      the performance of the MIPs prepared with those trifunctional cross-linkers. The
      combination of a hydrogen bonding functional monomer (acrylamide) with TRIM also
      did not give improved recognition. The results suggest that although the three
      dimensional network of these two kinds of polymer may be quite different, the
      observed recognition improvements were probably largely due to solvent effect.

PMID- 10949472
TI  - Titania as a sorbent in normal-phase liquid chromatography.
AB  - "Sachtopore" a titanium dioxide sorbent for HPLC is compared to a silica, an
      alumina and a zirconia sorbent with regard to its physical and chemical
      properties and examples for chromatographic separations are given. Titania has
      hydroxyl groups on its surface that are only slightly acidic so that native
      titania can be used to separate basic molecules under normal-phase conditions. It
      is shown that this enables the purification of basic fine chemicals and
      pharmaceuticals. Also, a number of examples for the separation of non-basic
      isomeric substances mixtures are presented.

PMID- 10949474
TI  - On-line monitoring of enantiomer concentration in chiral simulated moving bed
      chromatography.
AB  - Simulated moving bed chromatography is a key technology for the pilot and
      production scale separation of enantiomers of chiral chemical species. Product
      quality control is probably the most important issue in this kind of separation
      at both scales, and for this it is clear that on-line monitoring of absolute
      enantiomer concentrations plays a major role. In this work, an on-line system
      consisting of a UV detector and a polarimeter in series is used to monitor the
      composition of the extract and raffinate streams of a laboratory SMB unit. The
      model system adopted is the separation of the enantiomers of the Troger's base on
      microcrystalline cellulose triacetate (CTA) using ethanol as mobile phase. The
      technique is effective and accurate, thus providing promising perspectives for
      SMB process control and dynamic optimization.

PMID- 10949475
TI  - Evaluation of major active components in St. John's Wort dietary supplements by
      high-performance liquid chromatography with photodiode array detection and
      electrospray mass spectrometric confirmation.
AB  - A RP-HPLC method with photodiode array detection and LC-electrospray ionization
      (ESI) MS confirmation was established for the determination of major active
      components in St. John's Wort dietary supplement capsules. The samples
      alternatively were extracted with ethanol-acetone (2:3) using a 55 degrees C
      water-bath shaker or an ambient temperature ultrasonic bath. Extracts were
      separated by RP-C18 chromatography using a 95-min water-methanol-acetonitrile
      trifluoroacetic acid gradient. The major components were identified by photodiode
      array detection and then confirmed by LC-ESI-MS. The quantification of components
      was performed using an internal standard (luteolin). This method may serve as a
      valuable tool for the quality evaluation of St. John's Wort dietary supplement
      products.

PMID- 10949476
TI  - High-performance ion-pair chromatographic behaviour of conjugated bile acids with
      di-n-butylamine acetate.
AB  - This paper dealt with a simple and efficient method for separating a mixture of
      different series of ionic, high polar, and hydrophilic conjugates of bile acids
      by high-performance ion-pair chromatography (HPIPC) with a new volatile ion-pair
      chromatographic reagent, di-n-butylamine acetate (DBAA), as a mobile phase
      additive. The substrates examined included eleven different classes of C-24
      glycine- or taurine-amidated, 3-sulfated, 3-glucosylated, 3-N
      acetylglucosaminidated, and 3-glucuronidated conjugates of cholic,
      chenodeoxycholic, urosodeoxycholic, and deoxycholic acids, as well as their
      double-conjugated forms. The anionic conjugated bile acids were chromatographed
      on a C18, reversed-phase ion-pair column, eluting with methanol-water (65:35,
      v/v) containing 5 mM of DBAA as a counter ion. Satisfactory chromatographic
      separation and column performance were attained by DBAA, compared with
      conventionally used non-volatile tetra-n-butylammonium phosphate. The present
      HPIPC method with DBAA provides an insight into the separation and structural
      elucidation of these biologically important bile acid conjugates and may be
      proved to be applied to HPLC-mass spectrometric analysis.

PMID- 10949477
TI  - Identification of atranorin and related potential allergens in oakmoss absolute
      by high-performance liquid chromatography-tandem mass spectrometry using negative
      ion atmospheric pressure chemical ionization.
AB  - This paper describes the first high-performance liquid chromatographic-tandem
      mass spectrometric method for the identification of atranorin and related
      potential allergens in oakmoss absolute. Oakmoss absolute is ubiquitous in the
      fragrance industry and is a key component in many fine perfumes. However, oakmoss
      absolute causes an allergic response in some individuals. Research is focused
      toward establishing the identity of the compounds causing the allergic response
      so a quality controlled oakmoss with reduced allergenic potential can be
      prepared. Consequently a highly selective and specific analytical method is
      necessary to support this effort. This is not available with the existing HPLC
      methods using UV detection.

PMID- 10949478
TI  - Determination of aldicarb, aldicarb sulfoxide and aldicarb sulfone in some fruits
      and vegetables using high-performance liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry.
AB  - An analytical method for the determination of aldicarb, and its two major
      metabolites, aldicarb sulfoxide and aldicarb sulfone in fruits and vegetables is
      described. Briefly the method consisted of the use of a methanolic extraction,
      liquid-liquid extraction followed by solid-phase extraction clean-up. Afterwards,
      the final extract is analyzed by liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry (LC-APCI-MS). The specific fragment ion
      corresponding to [M-74]+ and the protonated molecular [M+H]+ ion were used for
      the unequivocal determination of aldicarb and its two major metabolites. The
      analytical performance of the proposed method and the results achieved were
      compared with those obtained using the common analytical method involving LC with
      post-column fluorescence detection (FL). The limits of detection varied between
      0.2 and 1.3 ng but under LC-FL were slightly lower than when using LC-APCI-MS.
      However both methods permitted one to achieve the desired sensitivity for
      analyzing aldicarb and its metabolites in vegetables. The method developed in
      this work was applied to the trace determination of aldicarb and its metabolites
      in crop and orange extracts.

PMID- 10949479
TI  - High-performance liquid chromatographic determination of the riboflavin
      concentration in white wines for predicting their resistance to light.
AB  - This research paper describes a new application in the field of quality control
      of white wine. A high-performance liquid chromatography analysis of riboflavin
      was used together with a simple sensorial test to produce a classification of
      wines, rating their susceptibility to exposure to light. Based on a wide survey
      covering 85 commercial white wines of different varieties in three countries
      (Italy, Spain and Slovenia), an average value of riboflavin of 98.63 microg/l
      with a rather high standard deviation of 41.91 microg/l, and a normal
      distribution was obtained. Our statistical study of the frequency distribution of
      the sensorial scores of light-exposed wines by means of the Expectation
      Maximization algorithm demonstrated that a large majority (71%) of these products
      were susceptible to the light, 31% of them belonging to the most severely
      affected group. Content of riboflavin was correlated with severity of appearance
      of the off-flavor in light-exposed white wines. These methods are directly
      applicable in the quality control of wine, being a valuable aid for oenologists
      in choosing appropriate fining protocols to reduce the appearance of the
      undesired "sunlight flavor" in bottled products.

PMID- 10949480
TI  - Comparison of different immunoaffinity clean-up procedures for high-performance
      liquid chromatographic analysis of ochratoxin A in wines.
AB  - Three immunoaffinity clean-up procedures to analyse ochratoxin A (OTA) in wines
      were compared. The direct wine clean-up with Ochraprep and OchraTest columns gave
      equivalent results in terms of recovery and precision if compared with the
      reference procedure involving a preliminary extraction of OTA with chloroform.
      OTA quantification limit in wine ranged from 0.020 to 0.045 microg/l. The 'on
      flow' OTA emission spectrum (excitation 333 nm) showed a maximum at 460 nm and
      could be used to confirm the quantitative results. The analysis of 11 red and
      white wines gave no significant quantitative differences between the three clean
      up techniques.

PMID- 10949481
TI  - Behavior of lanthanides in countercurrent chromatography using dihexyl-N,N
      diethylcarbamoyl methylene phosphonate as stationary phase.
AB  - Counter-current chromatography is a real liquid-liquid chromatography. The
      retention volume of the solute can be calculated from the batch distribution
      ratio in organic separations. In the separations of metal ion, there are several
      complex and dissociation reactions involved in the two phases, and the retention
      volume cannot be always predicted from the batch distribution ratio. A mass
      transfer model is proposed in this paper and an expression of V(R) is derived.
      The retention volume of metal ion is determined not only by the batch
      distribution ratio but also by the mechanism of the extraction reaction. When 25%
      dihexyl-N,N-diethylcarbamoyl methylenephosphonate in cyclohexane is used as
      stationary phase and 2.91 mol/l HNO3 as mobile phase, the dynamic distribution
      ratios obtained from the chromatogram are not equal to but proportional to the
      batch distribution coefficients. These results are in agreement with the
      theoretical expression.

PMID- 10949482
TI  - Analysis of heavy metals in atmospheric particulate by ion chromatography.
AB  - Cu, Ni, Zn, Co, Fe+2, Mn, Cd, Fe+3 and Pb are easily separated and detected in
      isocratic mode by ion chromatography with post-column derivatization using a
      bifunctional ion-exchange column and an eluent formed by oxalic acid (28 mM) and
      sodium nitrate (250 mM). The separation is optimised by using a suggested sample
      solution containing a given concentration of chloride. Detection limits were 10
      15 ppb for all the metals except for cadmium and lead, for which detection limits
      of 30 and 60 ppb were found, respectively. The method was tested on an
      atmospheric particulate certified sample. The measured values were in good
      agreement with certified values. Real samples of atmospheric particulate from
      industrial and urban sites were analysed and the results are discussed.

PMID- 10949483
TI  - Improved method for the determination of trace perchlorate in ground and drinking
      waters by ion chromatography.
AB  - Ammonium perchlorate, a key ingredient in solid rocket propellants, has been
      found in ground and surface waters in a number of U.S. states, and perchlorate
      contamination of public drinking water wells is now a serious problem in
      California. Perchlorate poses a health risk and preliminary data from the U.S.
      EPA reports that exposure to less than 4-18 microg/l provides adequate human
      health protection. An improved ion chromatographic method was developed for the
      determination of low microg/l levels of perchlorate in ground and drinking waters
      based on a Dionex IonPac AS16 column, an hydroxide eluent generated using an EG40
      automated eluent generator, large loop (1000 microl) injection, and suppressed
      conductivity detection. The method is free of interferences from common inorganic
      anions, linear over the range of 2-100 microg/l perchlorate, and quantitative
      recoveries are obtained for low microg/l levels of perchlorate in spiked ground
      and drinking water samples. The MDL of 150 ng/l permits quantification of
      perchlorate below the levels that ensure adequate health protection.

PMID- 10949484
TI  - Group method approach to the estimation of response factors of unavailable
      substances in quantitative gas chromatography.
AB  - The method's accuracy of a compound quantitation by chromatography depends on the
      calibration procedure with a pure standard of the target analyte, if the latter
      is unavailable uncertainty is unavoidable. The group method is a different
      approach in GC quantitative analysis that shows a practicable way for avoiding
      this uncertainty and accurately quantify a mixture containing one or more
      unavailable components. This paper is concerned with the definition of the group
      method quantitative parameters, the application procedures for their calculation,
      the determination of the quantitative proportion of a group of unavailable
      components of a mixture and the partial or total quantitation of the latter. The
      paper also describes the steps for carrying out the so-called group-correlation
      method in the determination of the response factors of unavailable compounds,
      which belong to a homologous series. The GC experimental corroboration of the
      group method approach employing model mixtures of compounds is also presented.

PMID- 10949485
TI  - Surface characterization of industrial fibers with inverse gas chromatography.
AB  - Inverse gas chromatography (IGC) was applied for the determination of the surface
      characteristics of Tenax carbon fibers and Akzo Nobel Twaron fibers. Furthermore,
      IGC procedures for the determination of dispersive and acid-base interactions
      were validated. The data show that too high values for the dispersive component
      of the surface energy are obtained when the adsorption area occupied by a single
      adsorbed n-alkane molecule is estimated from parameters of the corresponding
      liquid. Comparable values are obtained when the Doris-Gray methodology (area per
      methylene unit) or measured probe areas are employed. For the fibers studied in
      this work meaningful Gibbs energy values of the acid-base interaction were only
      obtained with the polarizability approach. When the dispersive interaction of the
      polar probes with the fiber surface was scaled to the n-alkane interaction via
      surface tension, the boiling point, or the vapor pressure of the probes often
      negative acid-base interaction energies were found. From the temperature
      dependence of the Gibbs energy, the enthalpy of the acid-base interactions of
      various probes with the carbon and Twaron aramid fibers was determined. However,
      from these enthalpy values no meaningful acid-base surface parameters could be
      obtained. Generally, the limited accuracy with which these parameters can be
      obtained make the usefulness of this procedure questionable. Also the Gibbs
      energy data of acid-base interaction can provide a qualitative basis to classify
      the acidity-basicity of the fiber surface. This latter approach requires only a
      limited data set and is sufficiently rapid to enable the use of IGC as a
      screening tool for fibers at a production site. For several polar probes
      significant concentration effects on carbon fibers were observed. At very low
      probe loadings the interaction with the fiber surface suddenly increases. This
      effect is caused by the heterogeneity of the interaction energy of the active
      sites at the surface. A simple procedure to measure the adsorption isotherm at
      infinite dilution was developed. The determination of the concentration
      dependence of the interaction of an n-alkane, an acidic and a basic probe was
      incorporated in the IGC screening procedure of carbon fibers to monitor this
      heterogeneity.

PMID- 10949486
TI  - Mixed-level orthogonal array design for the optimization of solid-phase
      extraction of some pesticides from surface water.
AB  - An orthogonal array design (OAD), OA32(4(1) x 2(28)), was employed as a
      chemometric method for the optimization of the solid-phase extraction (SPE) of
      atrazine, diazinon, ametryn and fenthion in surface water. Seven parameters: the
      type of eluting solvent, type of sorbent, flow-rate of eluting solvent, sample
      pH, sample volume, elution volume, addition of modifier and flow-rate of water
      sample were studied and optimized by a mixed-level OAD. The effects of these
      factors and some two-variable interactions on the recovery of the pesticides were
      quantitatively evaluated by the analysis of variance and percentage contribution
      techniques. The final optimized condition was employed for the SPE of selected
      micro-organic pollutants from Karoun river water, south of Iran. Atrazine and
      ametryn were tentatively identified and determined at the 0.7 and 0.9 microg l(
      1) level, respectively.

PMID- 10949487
TI  - Number-average molecular mass determination of polymeric material by pyrolysis
      gas chromatography.
AB  - The number-average molecular mass of a polymeric material has been determined by
      pyrolysis-gas chromatography (Py-GC) via end-group analysis. The major advantage
      of this technique is that no sample preparation is required. The sample is not
      required to be in the dilute solution form, and the amount of sample needed is
      approximately 0.5 mg. Phenyl group-terminated polybutadiene systems have been
      studied as an example. The application of Py-GC to obtain the end-group
      concentration, the number-average molecular mass and the limitations of this
      method are discussed in detail. The success of this development elevates the role
      of Py-GC as an important technique for end-group analysis for the determination
      of number-average molecular mass.

PMID- 10949488
TI  - Open access capillary electrophoresis. A walk up capillary electrophoresis
      service for the synthetic chemist.
AB  - A capillary electrophoresis (CE) system has been developed to provide routine
      purity information to support synthetic organic chemists. A single micellar
      electrokinetic chromatography system that produces good selectivity with short
      run times was developed. The instrument operating software has been modified to
      run separations in a custom open access mode. No expert knowledge of CE is
      required to run separations.

PMID- 10949489
TI  - Characterization of chemical selectivity in micellar electrokinetic
      chromatography. VI. Effects of surfactant counter-ion.
AB  - Linear solvation energy relationships and free energy of transfer data were used
      to evaluate the influence of the surfactant counter-ion on selectivity in
      micellar electrokinetic chromatography. It was determined that selectivity
      differences are dependent on the valency of the counter-ion but not the type of
      counter-ion. Monovalent surfactants, sodium dodecyl sulfate (SDS) and lithium
      dodecyl sulfate, have nearly identical selectivity behavior. The divalent
      surfactants, magnesium didodecyl sulfate and copper didodecyl sulfate also show
      very similar behavior. However, when the divalent counter-ion species is compared
      to SDS under similar conditions, significant differences are observed. Most
      notably, the utilization of divalent counter-ion species of dodecyl sulfate
      surfactants causes the micelles to become more hydrophobic and a weaker hydrogen
      bond donating pseudo-stationary phases. It is believed that the divalent counter
      ions reduce the electrostatic repulsion between the surfactant head groups and
      therefore, increase the chain packing of the monomers in the micelle aggregates.
      This reduces the degree of hydration of the micellar palisade layer leading to a
      decreased ability of the micelle to participate in polar/polarizable and hydrogen
      bonding interactions with solute molecules.

PMID- 10949490
TI  - Transient state of chiral recognition in a binary mixture of cyclodextrins in
      capillary electrophoresis.
AB  - The transient state (as the defined point where no enantioseparation is obtained
      in a dual chiral selector system) of chiral recognition of aminoglutethimide in a
      binary mixture of neutral cyclodextrins (CDs) was studied by capillary
      electrophoresis (CE). The following three dual selector systems were used: alpha
      cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-CD); alpha-CD and heptakis(di
      O-methyl-beta-cyclodextrin) (DM-beta-CD); alpha-CD and heptakis(tri-O-methyl-beta
      cyclodextrin) (TM-beta-CD). The S-(-) enantiomer of the analyte was more strongly
      retained in the presence of either alpha-CD or TM-beta-CD at pH 2.5, 100 mM
      phosphate buffer, while the R-(+) enantiomer was more strongly retained in the
      presence of either beta-CD or DM-beta-CD. In the more simple case, the elution
      order is invariably kept if the enantiomers have the same elution order in either
      one of the two hosts of the binary mixture. In contrast, the elution order may be
      switched by varying the concentration ratio of two hosts that produce opposite
      elution order for this particular analyte. In such a dual selector system, the
      enantioselectivity will disappear at the transient state at a certain ratio of
      host1:host2. Moreover, the migration times of the two enantiomers with host,
      alone (diluted in buffer) is approximately equal to the migration times at the
      corresponding concentration of host2 alone (diluted in buffer), where the ratio
      of concentrations of host1:host2 is the same as in the binary mixture at the
      transient state. As found by nuclear magnetic resonance experiments, the analyte
      is forming a 1:1 complex with either one of the CDs applied. From this finding, a
      theoretical model based on the mobility difference of the two enantiomers was
      derived that was used to simulate the transient state.

PMID- 10949491
TI  - Separation of acidic solutes by nonaqueous capillary electrophoresis in
      acetonitrile-based media. Combined effects of deprotonation and
      heteroconjugation.
AB  - Nonaqueous capillary electrophoresis (NACE) is a chemical separation technique
      that has grown in popularity over the past few years. In this report, we focus on
      the combination of heteroconjugation and deprotonation in the NACE separation of
      phenols using acetonitrile (ACN) as the buffer solvent. By preparing various
      dilute buffers consisting of carboxylic acids and tetrabutylammonium hydroxide in
      ACN, selectivity may be manipulated based on a solute's dissociation constant as
      well as its ability to form heterogeneous ions with the buffer components. ACN's
      low viscosity, coupled with its ability to allow for heteroconjugation, often
      leads to rapid and efficient separations that are not possible in aqueous media.
      In this report, equations are derived showing the dependence of mobility on
      various factors, including the pKa of the analyte, the pH and concentration of
      the buffer, and the analyte-buffer heteroconjugation constant (Kf). The validity
      of these equations is tested as several nitrophenols are separated at different
      pH values and concentrations. Using nonlinear regression, the Kf values for the
      heteroconjugate formation between the nitrophenols and several carboxylate anions
      are calculated. Also presented in this report are the NACE separations of the 19
      chlorophenol congeners and the 11 priority pollutant phenols (used in US
      Environmental Protection Agency methods 604, 625/1625 and 8270B).

PMID- 10949492
TI  - Investigations on the behaviour of acidic, basic and neutral compounds in
      capillary electrochromatography on a mixed-mode stationary phase.
AB  - This work describes the separation of acidic, basic and neutral organic compounds
      as well as inorganic anions in a single run by capillary electrochromatography
      employing a stationary phase which exhibits both strong anion-exchange and
      reversed-phase chromatographic characteristics. The positive surface charge of
      this stationary phase provided a substantial anodic electroosmotic flow. The
      analytes were separated by a mixed-mode mechanism which comprised chromatographic
      interactions (hydrophobic interactions, ion-exchange) as well as electrophoretic
      migration. The influence of ion-exchange and hydrophobic interactions on the
      retention/migration of the analytes could be manipulated by varying the
      concentration of a competing ion and/or the amount of organic modifier present in
      the background electrolyte. Additionally the effects of pH changes on both the
      chromatographic interactions as well as the electrophoretic migration of the
      analytes were investigated.

PMID- 10949493
TI  - Analysis of isomeric glutamyl peptides by capillary electrophoresis. Application
      to stability studies.
AB  - Capillary electrophoresis has been used for the separation of the glutamyl
      tripeptides Gly-alpha-Glu-Phe-NH2 and Phe-alpha-Glu-Gly-NH2 including their
      potential degradation and isomerization products Gly-gamma-Glu-Phe-NH2, alpha-Glu
      Phe-NH2, gamma-Glu-Phe-NH2 and Phe-NH2 as well as Phe-gamma-Glu-Gly-NH2, Phe-Glu
      and Phe, respectively. Between pH 2.2 and pH 10.0 the effective mobilities of the
      glutamyl peptides have been investigated. Using histidine hydrochloride as
      internal standard at pH 2.2 linear calibration curves for both assays were
      obtained for a concentration range from 10 microg ml(-1) to 3.5 mg ml(-1). The
      assay was applied to analyze the degradation of the tripeptides in solution at pH
      7 and pH 3 at 70 degrees C. Hydrolysis and isomerization of the glutamyl peptides
      were found in the incubation mixtures.

PMID- 10949494
TI  - Determination of ebrotidine and its metabolites by capillary electrophoresis with
      UV and mass spectrometry detection.
AB  - This study describes the application of capillary electrophoresis (CE) to the
      analysis of ebrotidine and its metabolites as an alternative analytical technique
      to liquid chromatography. Comparison between UV-diode array spectroscopy and mass
      spectrometry (MS) using an ion-trap system with electrospray ionization as
      detection systems has been performed. The quality parameters of the UV detection
      method were established, obtaining linear calibration curves over the range
      studied (8-200 mg ml(-1)), limits of detection between 3.4 and 4.3 microg ml(-1),
      and run-to-run and day-to-day precision lower than 14%. For these compounds the
      protonated species [M+H]+ and, in some cases, sodium adducts were observed in the
      MS spectra. Using MS coupled to CE, limits of detection were between 0.5 and 2.6
      microg ml(-1).

PMID- 10949495
TI  - Separation of metalloporphyrins by capillary electrophoresis with UV detection
      and inductively coupled plasma mass spectrometric detection.
AB  - Vitamin B12, cobalt protoporphyrin, manganese protoporphyrin, and zinc
      protoporphyrin were separated using capillary electrophoresis, and a comparison
      was made between detection with inductively coupled plasma mass spectrometry (ICP
      MS) and UV detection. Absolute limits of detection were slightly better with ICP
      MS detection than with UV detection, but for both methods absolute detection
      limits were in the picogram range. The migration times of the analytes decreased
      by several minutes when ICP MS detection was employed, and this phenomenon was
      believed to be a result of a "suction effect" that developed when the CE
      capillary was interfaced to the ICP-MS nebulizer. However, the resolution between
      species containing the same metal atom was not altered significantly, and the
      separation was completed in much less time relative to separations performed with
      UV detection.

PMID- 10949496
TI  - Simultaneous determination of eleven ingredients in ophthalmic solutions by
      cyclodextrin-modified micellar electrokinetic chromatography with
      tetrabutylammonium salt.
AB  - Cyclodextrin-modified micellar electrokinetic chromatography was applied to
      determine simultaneously 11 active ingredients in ophthalmic solutions. All the
      ingredients were successfully separated by using the mixed carrier system
      containing sodium dodecyl sulfate with beta-cyclodextrin and tetrabutylammonium
      phosphate. The effects of the cyclodextrin type on selectivity were also
      examined. Excellent separation of the all ingredients was obtained by the use of
      dimethyl-beta-cyclodextrin. The established method was validated and confirmed to
      be applicable to the determination of the active ingredients in a commercial
      ophthalmic solution. These results suggest that capillary electrophoresis can be
      applied to the quantitative analysis as well as qualitative analysis in
      pharmaceuticals.

PMID- 10949497
TI  - Analysis of highly saline samples by capillary zone electrophoresis: enhanced
      direct UV detection of inorganic anions using on-capillary preconcentration and
      clean-up techniques.
AB  - The ability to analyze samples with disparate levels of analyte and matrix ions
      is among the important benefits defining the practical utility of modern
      capillary electrophoresis. To compensate for the sensitivity limitations
      regarding trace-level inorganic anions, a number of on-line approaches that
      should offer an improved S/N ratio in direct UV detection were examined. The
      novel use of reversed pre-electrophoresis (at the applied voltage opposite to the
      separation voltage) made it possible to efficiently remove the most part of high
      chloride levels from the sample and hence to lower the background signal and to
      inject increased quantities of fast analyte anions. Specifically, by taking these
      advantages the sensitivity response of iodide was improved by a factor of 5 over
      normal CE mode. Using isotachophoretic sample stacking, a two-fold increase in
      detectability was obtained for moderately mobile anions, nitrate and nitrite,
      that corresponds to the minimum detectable concentrations close to their natural
      occurrences in seawater. Furthermore, field-amplified sample injection at
      increased electrolyte-to-sample matrix concentration ratios enabled the maximum
      S/N enhancement, with detection limits at the level of 10(-6) M and lower in the
      presence of > or = 5 x 10(4)-fold molar excess of chloride.

PMID- 10949498
TI  - Determination of ochratoxin A in domestic and imported beers in italy by
      immunoaffinity clean-up and liquid chromatography.
AB  - A method first developed to quantify ochratoxin A in wine has been applied to the
      analysis of domestic and imported beers in Italy. The method uses commercial
      immunoaffinity columns for clean-up and high-performance liquid chromatography
      for quantification of the toxin. Beer was degassed, then diluted with a
      polyethylene glycol-sodium hydrogencarbonate solution and applied to an OchraTest
      immunoaffinity column. Ochratoxin A was eluted from the immunoaffinity column
      with methanol and quantified by reversed-phase HPLC with fluorometric detector.
      Average recoveries of ochratoxin A from blank beer spiked at levels from 0.04 to
      1.0 ng/ml ranged from 93.8% to 100.4%, with relative standard deviations between
      3.3% and 5.7%. The detection limit was 0.01 ng/ml based on a signal-to-noise
      ratio of 3:1. The analysis of 61 samples of domestic (10) and imported (51) beers
      showed ochratoxin A levels ranging from <0.01 to 0.135 ng/ml with an incidence of
      contamination of 50% and no substantial difference between strong and pale beers.

PMID- 10949499
TI  - Simultaneous extraction and derivatization of 2-chlorovinylarsonous acid from
      soils using supercritical and pressurized fluids.
AB  - Supercritical carbon dioxide and pressurized fluids are compared for the
      extraction with in situ derivatization of 2-chlorovinylarsonous acid (CVAA) from
      a series of seven spiked soils. Samples are allowed to age (up to 42 days) and
      periodically extracted. Sample ageing leads to a recovery decrease due to the
      development of strong interactions between CVAA and matrix active sites, as time
      elapses. A similar behavior is observed when usual ultrasonic extraction is
      performed. Supercritical fluid extraction (SFE) with in situ derivatization leads
      to the highest recovery. Moreover, SFE allows a solvent consumption reduction. A
      limit of detection of 0.2 microg/g is reached with the SFE method.

PMID- 10949500
TI  - Comparison of the thin-layer chromatographic properties of sulfur-containing
      amino acids and their aminophosphonic analogues.
AB  - The thin-layer chromatographic behavior of the natural, sulfur-containing amino
      acids (Cys, Hcys, Met) and their phosphonic analogues (CysP, HcysP, MetP) has
      been studied. Their detection limits using iodine and molybdate, ninhydrine and
      iodine-azide reagents were determined, and the R(F) values of these two classes
      of amino acids in acidic, neutral and mild basic solvent systems were compared.

PMID- 10949501
TI  - Identification of tibial stress fractures using therapeutic continuous
      ultrasound.
AB  - STUDY DESIGN: One-group discriminant analysis. OBJECTIVE: To determine whether 1
      MHz of continuous ultrasound can identify tibial stress fractures in subjects.
      BACKGROUND: Stress fractures can lead to loss of function or to more serious
      nonunion fractures. Early diagnosis is important to reduce the risk of further
      injury and to assure a safe return to activity. Therapeutic ultrasound has been
      reported to be an accessible, less expensive alternative in diagnosing stress
      fractures compared with other diagnostic techniques. METHODS AND MEASURES: Twenty
      six subjects (12 men, 20.33 +/- 1.37 years; 14 women, 20.78 +/- 3.8 years) with
      unilateral tibia pain for less than 2 weeks volunteered to participate in the
      study. Continuous, 1 MHz ultrasound was applied to the uninvolved and involved
      tibias at 7 increasing intensities for 30 seconds each. Subjects completed a
      visual analog scale after the application of each intensity to assess the pain
      response to ultrasound. Results from the visual analog scale were compared to
      magnetic resonance imaging (MRI) findings to determine if continuous ultrasound
      could predict whether subjects had a normal MRI, increased bone remodeling, or
      advanced bone remodeling consistent with a stress fracture. RESULTS: Discriminant
      analysis on the visual analog scale correctly classified subjects into 1 of 3
      clinical classification groups in 42.31% of the cases. None of the subjects found
      to have a stress fracture by MRI were correctly identified by continuous
      ultrasound. This resulted in a predicted sensitivity of 0% and a predicted
      specificity of 100%. CONCLUSIONS: A protocol using visual analog scores after the
      application of 1 MHz continuous ultrasound is not sensitive for identifying
      subjects with tibial stress fractures.

PMID- 10949502
TI  - Role of manual therapy in the evaluation and treatment of a surgically stabilized
      pelvis.

PMID- 10949503
TI  - Differential diagnosis and treatment for a patient with lower extremity symptoms.

PMID- 10949504
TI  - Relationships between plantar flexor muscle stiffness, strength, and range of
      motion in subjects with diabetes-peripheral neuropathy compared to age-matched
      controls.
AB  - STUDY DESIGN: Descriptive study to compare relationships between muscle
      performance measures in 2 subject groups. OBJECTIVES: To determine the
      relationships between plantar flexor (PF) muscle stiffness, strength (concentric
      peak torque), and dorsiflexion (DF) range of motion (ROM) in subjects with
      diabetes who have peripheral neuropathy (n = 17, 10 men, 7 women; age = 58 +/- 11
      years) and age-matched controls (n = 17, 10 men, 7 women; age = 62 +/- 6 years).
      BACKGROUND: The relationships between muscle stiffness, strength, and joint ROM
      have not been clearly established. Furthermore, the effect of neuromuscular
      pathology on these relationships is unknown. METHODS AND MEASURES: PF stiffness
      and strength measurements were obtained with an isokinetic dynamometer. DF ROM
      was measured with a goniometer. A Pearson correlation matrix was constructed for
      each subject group using stiffness, strength, and ROM variables. The percent
      contribution of passive torque to total torque was computed at 2 joint angles.
      RESULTS: In subjects with diabetes and peripheral neuropathy (DM-PN) peak
      concentric PF torque was positively correlated with passive torque at 5 degrees
      DF (r = 0.77), Stiffness #1 (r = 0.58), and Stiffness #2 (r = 0.50). The
      percentage of passive PF torque at 5 degrees DF was greater in subjects with DM
      PN, compared to control subjects (29.3 +/- 9.4% versus 12.6 +/- 5.9%).
      CONCLUSIONS: The positive correlation between PF stiffness and strength, and the
      greater percentage of passive PF torque in subjects with DM-PN suggest that
      patients with decreased strength may use passive torque to maximize total torque.
      Therefore, treatment methods designed to decrease stiffness should be used
      cautiously.

PMID- 10949505
TI  - Discriminant validity of temporomandibular joint range of motion measurements
      obtained with a ruler.
AB  - STUDY DESIGN: Prospective, descriptive study. OBJECTIVE: To determine the
      discriminant validity and intrarater and interrater reliability of measurements
      of temporomandibular joint (TMJ) range of motion (ROM). BACKGROUND: Although ROM
      measurements are a routine part of the examination of patients with TMJ
      disorders, few studies have examined the validity of these measures for
      identifying pathology of the TMJ. METHODS AND MEASURES: Two groups of subjects
      were tested: 15 subjects (2 men, 13 women; mean age = 35.2 years) with a TMJ
      disorder and 15 subjects (3 men, 12 women; mean age = 42.9 years) without a TMJ
      disorder. Six motions were measured (opening, left excursion, right excursion,
      protrusion, overbite, and overjet) by 2 therapists. RESULTS: Mouth opening was
      the only TMJ ROM measurement to discriminate between subjects with and without
      TMJ disorders (mean 36.2 +/- 6.4 versus 43.5 +/- 6.1 mm). The technical error of
      measurement of the measures varied from .2 to 2.5 mm. Intrarater reliability
      coefficients (ICC 3,1) varied from .70 to .99. Interrater reliability
      coefficients (ICC 2,k) varied from .90 to 1.0. CONCLUSIONS: Although all TMJ ROM
      measurements tended to be reliable, only mouth opening was found to be valid in
      discriminating between patients with and without a TMJ disorder.

PMID- 10949506
TI  - Disablement model inadequate.

PMID- 10949507
TI  - Pathology and anatomy not part of disablement model.

PMID- 10949508
TI  - Workshops propose national programme for veterinary helminthology for South
      Africa.
AB  - A workshop was held at Onderstepoort on 2-3 July 1999 to set priorities in
      veterinary helminthology for South Africa. Representatives from 19 organisations
      attended. The workshop achieved 2 of its 3 aims, namely to identify the priority
      areas within the field and to set specific objectives to be achieved in
      addressing these needs. Seven strategies were proposed, namely, motivation,
      education, therapeutic, worm resistance, animal tolerance, biological control and
      diagnostic strategies. A follow-up session took place on 8 September 1999 and at
      this workshop and in subsequent meetings, preliminary action plans were developed
      for these strategies. It was felt that the proposed activities delineated by this
      process should form the basis for a National Programme for Veterinary
      Helminthology and a national forum is to be convened to encourage all
      stakeholders to consider, discuss and adopt these activities. The forum is
      scheduled to take place in April 2000.

PMID- 10949509
TI  - A krimpsiekte-like syndrome in small stock poisoned by Ornithogalum toxicarium
      Archer & Archer.
AB  - Krimpsiekte (the syndrome associated with chronic cardiac glycoside poisoning)
      was purportedly induced by Ornithlogalum toxicarium in the Karas mountains area
      of Keetmanshoop, Namibia. This chinkerinchee species was previously linked to a
      condition known as 'kwylbek' krimpsiekte in small stock in the Beaufort West
      district of the Western Cape Province, South Africa. In a dosing trial,
      respiratory distress, tachycardia and sternal recumbency were observed in 2 sheep
      drenched with fresh plant material. A fluorescence polarisation immunoassay
      (FPIA) detected the presence of a substance that cross-reacted with digoxin
      antibodies in some of the plant material collected at Keetmanshoop and Beaufort
      West. This is the first time that apparent cardiac glycoside poisoning was
      induced by a southern African chinkerinchee species. The presence of the cardiac
      glycoside-like substance in O. toxicarium requires further chemical verification.

PMID- 10949510
TI  - The prevalence of bovine viral diarrhoea antibodies in selected South African
      dairy herds, and control of the disease.
AB  - The prevalence of bovine viral diarrhoea (BVD) serologically positive animals in
      18 dairy herds with clinical and pathological lesions suggestive of BVD
      infection, the post-vaccinal seroconversion rates in negative animals vaccinated
      twice with an inactivated BVD vaccine, and the control measures taken, are
      described. The pathological and histopathological findings in 6 necropsies
      performed on animals that died in 5 separate herds closely resembled published
      descriptions. Positive immunohistochemistry results in 3 cases confirmed the
      diagnosis in those animals. In 1 herd the prevalence of prevaccinal BVD
      antibodies was only 36.8%, while the prevalence varied from 79.85 to 100% in the
      remainder. Control measures taken included immunoprophylaxis with an inactivated
      vaccine, culling animals that were serologically negative after vaccination that
      were regarded as probably persistently infected (PI) and the implementation of
      additional biosecurity measures. The prevalence of serologically negative PI
      animals in 10 herds varied from 0.38 to 4.04%, with 8 herds less than 1% and 2
      herds at 2.79% and 4.04%, respectively. Methods based on vaccinating the herd,
      followed by serological testing and culling cattle that did not develop an
      antibody titre, are not reliable. The identification of PI animals should be
      confirmed by isolation of the virus or identification of the antigen.

PMID- 10949511
TI  - Blood pressure changes in dogs with babesiosis.
AB  - Systemic arterial blood pressures were measured in 30 dogs with acute babesiosis,
      10 each with mild uncomplicated, severe uncomplicated and complicated disease.
      Ten healthy dogs were used as controls. Hypotension was defined as more than 3
      standard deviations below the control mean. Normal mean pressures (+/-SD) were:
      systolic arterial pressure 151 (+/-11) mm Hg, diastolic arterial pressure 89 (+/
      8) mm Hg and mean arterial pressure 107 (+/-10) mm Hg. Hypotension was the most
      frequent abnormality, and increased strikingly in incidence as disease severity
      increased, with 5/10 dogs in the complicated group being hypotensive for
      systolic, diastolic and mean arterial pressures, compared with 2/10 in the severe
      uncomplicated group and 0/10 in the mild uncomplicated group. Systolic, diastolic
      and mean arterial pressures in the complicated group and severe uncomplicated
      group, and systolic pressure in the mild uncomplicated group, were significantly
      lower than in the controls. There were no significant relationships between
      arterial pressures and age, pulse rate, respiratory rate, temperature, mucous
      membrane colour or haematocrit. There was a significant negative correlation
      between arterial pressures and white cell and immature neutrophil counts.
      Arterial pressures differed significantly between dogs that were clinically
      collapsed and those that were not, but not between survivors and non-survivors.
      Pulse pressure (systolic-diastolic) was low in 7/10 complicated, 1/10 mild
      uncomplicated, and 1/10 severe uncomplicated cases, and differed significantly
      between the complicated and control groups. The high incidence of hypotension in
      clinically severe babesiosis has important implications for therapy.

PMID- 10949512
TI  - Babesia bovis and B. bigemina DNA detected in cattle and ticks from Zimbabwe by
      polymerase chain reaction.
AB  - From blood collected from 94 cattle at 12 locations in the eastern and
      northeastern areas of Zimbabwe, DNA was extracted and analysed by polymerase
      chain reaction with primers previously reported to be specific for Babesia
      bigemina and Babesia borvis. Overall, DNA of Babesia bigemina was detected in the
      blood of 33/94 (35%) cattle and DNA from B. bovis was detected in 27/58 (47%) of
      cattle. The prevalence of DNA of B. bigemina was significantly higher in young
      animals (<2 years) (23/46) than in animals over 2 years of age (10/48; chi2=
      8.77; P <0.01%). Although tick sampling was not thorough, Boophilus decoloratus
      could be collected at 7/9 sites sampled and Boophilus microplus at 4/9 sites. Of
      the 20 B. decoloratus allowed to oviposit before PCR analysis, 1 (5%) contained
      DNA that could be amplified with primers for B. bigemina while 12 (60%) were
      positive with primers for B. bovis. Of the B. microplus allowed to oviposit,
      11/16 (69%) were positive for B. bovis DNA by PCR and 2/16 (12%) were positive
      for B. bigemina.

PMID- 10949513
TI  - The prevalence of subclinical mastitis in dairy goats in Kenya.
AB  - California mastitis test (CMT), direct leukocytes counts and bacteriological
      examination were performed on 630 milk samples from apparently healthy mammary
      glands of dairy goats comprising a mixed population of German Alpine, Toggenberg,
      Saanen and Galla crosses to find the prevalence of subclinical mastitis. The
      prevalence of subclinical mastitis was 9.8% according to CMT, 9.7% according to
      direct leukocyte counts and 28.7% by bacterial isolation during a 3-month period.
      The proportion of the bacteriologically positive milk samples was significantly
      (P <0.01) higher than that positive for CMT and direct leukocyte counts. There
      was a significant (P < 0.01) correlation between CMT and direct leukocyte counts.
      There was no significant direct relationship between bacterial isolation and CMT
      Bacterial organisms were isolated in 22.5% of the 568 CMT-negative milk samples.
      The results suggest that bacterial organisms isolated from the CMT-negative
      milksamples were either latent infections or did not stimulate any significant
      increase in somatic cell counts that could be detected by either the CMT or
      direct leukocyte counts. The observations of this study indicate that the mere
      presence of bacteria in goat's milk does not mean that the udder is infected and
      so does not warrant antibiotic therapy.

PMID- 10949514
TI  - Flystrike prevention on Merino lambs with the insect growth regulator dicyclanil.
AB  - The efficacy of a ready-to-use 5% dicyclanil pour-on formulation as a
      preventative of natural flystrike on Merino lambs was investigated in a field
      trial involving 5 sites in the southern Cape Province. A total of 1,804 lambs
      treated with dicyclanil were compared with 882 untreated control lambs for up to
      25 weeks after treatment. Efficacy was assessed by calculating the weekly
      cumulative strike rate at each site and aggregated for all sites, as well as by
      calculating the percentage reduction achieved in treated lambs. Cumulative strike
      rates for the untreated controls aggregated for all sites at Weeks 9,14 and 19
      after treatment reached 6.2, 12.8 and 17.8%, respectively, compared with 0.4, 1.7
      and 3.6% for the dicyclanil treated lambs. Percentage control aggregated for all
      sites at Weeks 9,14 and 19 after treatment was 93, 87 and 80%, respectively.
      Heavy rains during the 1st half of the trial did not substantially reduce the
      efficacy of the product.

PMID- 10949515
TI  - Effects of anthelmintic treatment and feed supplementation on grazing Tuli weaner
      steers naturally infected with gastrointestinal nematodes.
AB  - A study was carried out to determine the epidemiology of gastrointestinal
      nematodes in indigenous Tuli cattle and the effect of dietary protein
      supplementation and anthelmintic treatment on productivity in young growing
      cattle. Forty steers with an average age of 18 months were divided into 4 groups;
      1) fenbendazole (slow release bolus) and cottonseed meal (FCSM group), 2)
      fenbendazole (FBZ group), 3) cottonseed meal (CSM group) and 4) control (no
      cottonseed meal and no fenbendazole) (control group). Performance parameters
      measured included worm eggs per gram of faeces (EPG), packed cell volume (PCV),
      albumin and live-weight gain. Results showed that faecal worm egg counts were
      lower and PCV was higher in the FCSM and FBZ groups than in the CSM and control
      groups (P < 0.01). Weight gains were higher in the CSM and FCSM groups than in
      the FBZ and control groups (P < 0.05). The cost benefits of anthelmintic
      treatment and dietary supplementation were apparent in this study. The improved
      growth performance of the FCSM, FBZ and CSM groups reflected a financial gain
      over the controls on termination of the study. The dominant genera of
      gastrointestinal nematodes on faecal culture, pasture larval counts and necropsy
      were Cooperia and Haemonchus. The incidences of Trichostrongylus, Oesophagostomum
      and Bunostomum were low.

PMID- 10949516
TI  - A preliminary study on the serum protein response in canine babesiosis.
AB  - Total serum protein, albumin, globulin, globulin fractions (alpha, beta and gamma
      globulins) and an acute-phase protein (alpha1-acid glycoprotein) were evaluated
      in dogs with naturally occurring mild (Group 1), severe (Group 2) or complicated
      babesiosis (Group 3). Results showed that the total serum protein, albumin, A/G
      ratio and alpha globulins were statistically different between Groups 1 and 2.
      There was no statistical difference between groups with total, beta and gamma
      globulins. The findings from this study suggest that dogs with mild and severe
      babesiosis had low total serum proteins, albumin, A/G ratio and alpha globulins;
      dogs with complicated babesiosis showed no typical serum protein changes or
      patterns; and that there was no evidence of an acute-phase response detectable on
      serum protein electrophoresis in any of the 3 groups. A marked acute-phase
      response was, however, present, as measured by the alpha1-acid glycoprotein, in
      all 3 groups. As this was a retrospective study, the possibility that the
      observed responses were due in part to concurrent disease could not be excluded.

PMID- 10949517
TI  - Survey of the incidence, diagnosis, clinical manifestations and treatment of
      Spirocerca lupi in South Africa.
AB  - A questionnaire survey of 716 veterinary practices was undertaken to determine
      the incidence of Spirocerca lupi in dogs in South Africa. In total, 49% of the
      questionnaires were returned, indicating a possible incidence of 28%. Fewer than
      4 cases per year were recorded by 82% of the respondents; 4-12 by 14%; 12-24 by
      3%; and more than 48 by only 1%. No seasonal incidence was reported by 48% of the
      respondents. Large breeds were considered to be at greater risk by 43% of
      respondents. No specific age or sex was identified to be at higher risk. The most
      common complaints by owners and clinical findings were vomiting (46%), weight
      loss (27%), coughing (21%) or regurgitation (20%), although 14% of respondents
      reported no abnormal clinical findings. Diagnostic methods used were radiology
      (74%), endoscopy (27%), post mortem examination (34%) and faecal flotation (4%).
      Complications associated with S. lupi were reported by 76% of respondents, which
      included oesophageal neoplasia (41%), hypertrophic osteopathy (38%) and acute
      haemothorax (30%). Specific treatments were used by 58% of the respondents,
      whereas 42% of the respondents either used no treatment (72%) or recommended
      euthanasia (28%). Of the treatment group, 52% used ivermectin, 27% doramectin,
      13% other deworming drugs (benzimidazoles, nitroscanate), and 8% used disophenol.
      Sixty-three percent of the respondents considered their treatment ineffective,
      whereas 31% considered it effective, and 6% were unsure. The overall mortality
      rate was high.

PMID- 10949518
TI  - Prognostic indicators of post partum viability of kids born to Escherichia coli
      vaccinated or unvaccinated does.
AB  - This study was undertaken to determine some blood and other physiological
      parameters with potential for use as prognostic indicators of viability of
      newborn goat kids. Of the 143 kids born during the on-farm study, 97 were crosses
      of Galla x Small East African (SEA) and 46 were pure SEA. The SEA x Galla kids
      were 46 single males, with a mean body weight at birth of 2.77 +/- 0.22 kg, 43
      females with a mean body weight at birth of 2.36 +/- 0.76 kg and 5 and 3 sets of
      female and male twins (mean body weight at birth of 1.8 +/- 0.19 kg and 2.05 +/-
      0.07 kg for the female and male kids, respectively). The SEA kids comprised 36
      single male and female kids (mean body weight at birth of 2.48 +/- 0.04 kg and 10
      sets of twins (both male and female) (mean body weight at birth of 1.50 +/- 0.04
      kg ). Pre-suckling sera obtained on-station from kids born of does vaccinated
      against Escherichia coli (n = 8) and unvaccinated does (n = 7) had a total
      protein content of <40.0 g/l and no detectable levels of IgG and A or E. coli
      antibodies. Sera obtained 12 hours post partum) from kids that survived in both
      groups contained about 19-22 g of Ig g/l, 50-80 g total protein/l, blood glucose
      of >5 mmol/l and had an E. coli antibody titre of between 1/160 and 1/640. On the
      other hand, kids that died within 48 hours of birth (parturient deaths) and had
      been classified in categories 3 and 4 righting reaction had low (<40 g/l) total
      protein, low white blood cell count (4,000/ml) and low blood glucose
      concentration (<4.9 mmol/l). It is concluded that kids with delayed righting
      reaction (>45 minutes), low rectal temperature (<36 degrees C), low birth weights
      (<1.5 kg for singles and <1.0 kg for twins), low white blood cells (<4,000/ml),
      low (<2 mmol/l) blood glucose levels, low total protein (<40.0 g/l), low (<1:160)
      E. coli antibody titre and IgG (< or =3,350 mg/l) in sera obtained 12 hours after
      birth have a poor prognosis for survival.

PMID- 10949519
TI  - Screening of five drugs for efficacy against Babesia felis in experimentally
      infected cats.
AB  - The efficacy of 5 drugs was tested against experimental Babesia felis infection
      in domestic cats. Two of the drugs, rifampicin and a sulphadiazine-trimethoprim
      combination, appeared to have an anti-parasitic effect, but were inferior to
      primaquine. The other 3 drugs, buparvaquone, enrofloxacin and danofloxacin, had
      no significant anti-babesial effect.

PMID- 10949520
TI  - Capture and immobilisation of aardvark (Orycteropus afer) using different drug
      combinations.
AB  - Nine aardvarks (Orycteropus afer) were captured in the southern Free State, South
      Africa, for the placement of abdominal radio transmitters. Five combinations of
      ketamine hydrochloride with xylazine hydrochloride, midazolam or medetomidine
      hydrochloride were used to induce anaesthesia. In some cases the level of
      anaesthesia was maintained with 1.5% halothane. A mixture of ketamine
      hydrochloride and medetomidine hydrochloride was found to be most effective.
      Atipamizole reversed the affects of medetomidine hydrochloride, resulting in a
      smooth and full recovery within 8 minutes. The immobilisation and subsequent
      anaesthesia of these animals on cold winter nights resulted in hypothermia, and
      keeping the animals warm was essential to the success of the procedures
      undertaken. Reversal of the sedative medetomidine hydrochloride proved to be
      important, because animals that were released before they were fully conscious
      took refuge in their burrows so that care was impossible.

PMID- 10949521
TI  - Hypoxaemia and suspected pulmonary oedema in a Dorper ewe after diazepam-ketamine
      induction of anaesthesia.
AB  - Anaesthesia was required in an 18-month-old Dorper ewe scheduled for surgical
      repair of an abdominal hernia. Anaesthesia was induced with diazepam (0.15 mg/kg)
      and ketamine (6 mg/kg), and maintained with halothane in oxygen on a circle
      anaesthetic machine. Hypotension, hypoxaemia, cyanosis and pulmonary oedema were
      observed from the start of surgery, but the symptoms improved towards the
      completion of the procedure. The aetiology of this condition could not be
      established. It is suggested that propylene glycol, the organic solvent in the
      diazepam formulation, may have stimulated the release of vasoactive substances
      that resulted in pulmonary oedema.

PMID- 10949522
TI  - Presurgical lateralization of seizure focus and language dominant hemisphere with
      O-15 water PET imaging.
AB  - OBJECTIVES: The purpose of this study was to assess the value of same day blood
      flow PET in both the identification of the language dominant hemisphere and in
      the lateralization of the epileptic focus in patients who were preoperatively
      evaluated for complex partial seizures. METHODS: The charts of 24 patients who
      had temporal lobectomies for seizures were retrospectively reviewed. All PET
      scans were acquired by using O-15 water tracer (H2(15)O) in both resting and
      language activation conditions. PET language laterality results were compared to
      Intracarotid amytal procedure (IAP) results. For epileptic focus lateralizations,
      regions of interest (ROI) analysis of temporal lobes was performed on resting
      scans. RESULTS: IAP testing was discordant with PET language mapping in 1 out of
      24 cases. This patient had a decline in cognitive abilities as measured by
      postoperative neuropsychologic testing. For epileptic focus lateralization, the
      PET was highly sensitive (87%) and specific (100%). Lateralizations with the PET
      were in agreement with surgical sites in all cases. Eighteen patients (75%) were
      seizure free and 4 patients (17%) were significantly improved after surgery.
      CONCLUSION: The results suggest that O-15 water PET is sensitive and specific in
      both the lateralization of epileptic focus and the language dominant hemisphere
      and can be a cost-effective and noninvasive method in presurgical evaluation of
      patients with complex partial seizures.

PMID- 10949523
TI  - Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive
      functions in focal epilepsy.
AB  - OBJECTIVES: The aim of our study was to evaluate possible changes in nocturnal
      sleep, daytime somnolence and cognitive functions induced by add-on therapy with
      lamotrigine (LTG). MATERIAL AND METHODS: Thirteen patients affected by seizures
      resistant to common antiepileptic drugs (AEDs) underwent nocturnal
      polysomnographic monitorings, daytime somnolence evaluations and a
      neuropsychological battery before and after 3 months of treatment with LTG.
      RESULTS: With LTG therapy we observed a significant increase in REM sleep and a
      significant reduction in the number of entries into REM and stage shifts. No
      significant correlation was observed between the decrease in nocturnal
      epileptiform activity and the increase in REM sleep. Other sleep parameters were
      unmodified. No significant changes were observed in daytime somnolence and in
      cognitive performances. CONCLUSION: LTG may produce positive effects on epileptic
      seizures and interictal abnormalities without interfering negatively on REM
      sleep, with improvement of sleep stability and without changes in daytime
      somnolence and neuropsychological performances. For these reasons it could be an
      important drug for improving epileptic patients' quality of life.

PMID- 10949524
TI  - Recurrence after first cerebral infarction in young adults.
AB  - OBJECTIVE: We have investigated recurrence of stroke in a consecutive series of
      young adults, aged 16 to 45 years, after a first cerebral infarction. METHODS:
      From January 1, 1988 to December 31, 1996 we submitted those patients to a
      diagnostic protocol including angiographic, cardiological, and haematological
      investigations. The patients were followed at 6 month intervals up to December
      31, 1998. RESULTS: We have evaluated and followed-up 135 patients, 71 men and 64
      women, who were 3.99% of all the admitted stroke patients. At 12 months after
      stroke, 83 patients had returned to work, 40 patients were mildly to moderately
      handicapped, 4 were using a wheel-chair, and 8 had died. Follow-up was 26 to 123
      months (mean 68.8). Recurrence of stroke, always of ischaemic nature, was seen in
      15 patients (11.1%), 3 to 76 months after the first stroke (mean 27.4), for an
      annual incidence of 2.26%. Recurrence was significantly associated with Partial
      Anterior Circulation Syndrome and Haematological subtype of first stroke
      (respectively, P = 0.0209 and P = 0.0135, chi2 test), but not with age (< or = or
      > 35 years) or risk factors. Repetition of stroke was never fatal, but it caused
      heavy disability in 13 patients, 8 of whom had completely or nearly completely
      recovered after the first event. CONCLUSIONS: Our data suggest that recurrence of
      stroke is a major clinical problem also for the patients aged less than 45 years
      and that it might be more frequent with specific clinical syndromes and etiologic
      subtypes of first stroke.

PMID- 10949525
TI  - Apolipoprotein E (APOE) phenotype and APOE concentrations in multiple sclerosis
      and acute herpes zoster.
AB  - OBJECTIVES: There are three major isoforms of apolipoprotein E (apoE), namely
      apoE2, apoE3, and apoE4, that are products of three alleles
      (epsilon2,epsilon3,epsilon4) at a single gene locus on chromosome 19. It is well
      known that the presence of apoE4 increases the risk for the development of
      Alzheimer's disease and atherosclerosis. The aim of the study was to examine if
      apoE polymorphism or apoE levels contribute to the severity of the disease in
      patients with multiple sclerosis or the outcome of nerve damage in patients with
      herpes zoster infection. MATERIAL AND METHODS: We examined apoE phenotype of 105
      MS patients and 41 patients with herpes zoster. We also measured serum and
      cerebrospinal fluid (CSF) levels of apoE from 93 patients with definite MS using
      enzyme linked immunosorbent assay. RESULTS: There were no differences in apoE
      allele frequencies in MS or herpes zoster patients compared to the allele
      frequencies of controls. The levels of serum or CSF apoE did not differ from
      those of age-matched controls, nor did they correlate with the disease activity.
      CONCLUSION: We conclude that apoE does not contribute to the activity of MS or
      the outcome of herpes zoster.

PMID- 10949526
TI  - Short-term ventricular volume changes on serial MRI in multiple sclerosis.
AB  - Axonal loss is likely to be an important component of atrophy and the
      pathological substrate for the fixed disability of MS. To estimate the rate of
      central white matter reduction we investigated ventricular volume change and
      disease activity on monthly MRI in 19 patients over 6 months. At baseline,
      ventricular volumes were largest in primary progressive MS and smallest in
      relapsing-remitting MS. Over the study period ventricular volumes increased
      overall by 0.2% (F= 2.75, P = 0.02), but the percentage changes in relapsing
      remitting MS were much larger (median increase 14.9%). Lesion volumes were also
      highest at baseline in relapsing-remitting MS, but serial changes in ventricular
      volumes were not correlated with serial changes in lesions. This study shows that
      ventricular enlargement in MS may occur over short epochs, particularly in
      relapsing-remitting cases. However, the loss of central white matter volume
      observed in any brief period may be related to inflammatory activity that
      occurred in a preceding or earlier epoch, a delayed post-inflammatory
      degenerative process, or most likely, a combination of both.

PMID- 10949527
TI  - Diagnostic sensitivity of predicted F-wave latency by age, height, and MCV.
AB  - OBJECTIVES: The aim was to investigate whether minimum F-wave latency (Fmin)
      predicted by a multiple regression equation utilizing age, height, and motor
      nerve conduction velocity (MCV) (3-factor method) was clinically useful to detect
      Fmin abnormality in diabetic polyneuropathy (DP) and lumbosacral
      monoradiculopathy (RAD). MATERIALS AND METHODS: Thirty-one DP patients (ulnar,
      tibial, and peroneal nerves) and 66 RAD patients (peroneal nerve) were
      investigated. The specificity and sensitivity of the 3-factor method were
      compared to those obtained by a univariate (height) regression method (1-factor
      method) and another multivariate (height and age) regression method (2-factor
      method). RESULTS: In general satisfactory specificity was obtained with all three
      methods. In DP patients the tibial 3-factor method showed statistically lower
      sensitivity than the other two methods. There were no significant differences in
      diagnostic sensitivity among the three methods in two other nerves of the DP
      patients and the peroneal nerve of the RAD patients. CONCLUSION: The 3-factor
      method was useful to estimate Fmin in normal subjects, but it was of little value
      in increasing the diagnostic sensitivity in DP and RAD patients. The 2-factor
      method was more appropriate for detecting DP.

PMID- 10949529
TI  - Cognitive outcome after bacterial meningitis.
AB  - OBJECTIVE: To evaluate long-term cognitive deficits in unselected patients with
      previously diagnosed meningitis and to compare these deficits to neurologic and
      psychopathologic impairment. PATIENTS AND METHODS: Twenty-two unselected patients
      (mean age 52.5 +/- 17.1 years) were examined neurologically, psychiatrically, and
      psychometrically 30 +/- 11 months after the acute stage of bacterial meningitis.
      Results of psychometric tests were compared with clinical long-term deficits.
      Psychometric tests were additionally applied on 17 healthy controls (mean age
      49.2 +/- 14.2 years). RESULTS: Neurologic or psychopathologic symptoms were found
      in 16 patients. Psychometrically, the speed of cognitive processes and
      psychomotor performance, concentration, visuoconstructive capacity, and memory
      functions were reduced significantly in patients as compared to controls. Verbal
      intelligence was less affected than performance efficiency. Patients with
      pneumococcal meningitis had significantly lower test results than patients with
      other pathogens. The psychometric test results were only slightly related with
      clinical findings of the follow-up examination. CONCLUSION: Psychometric deficits
      are frequent after bacterial meningitis, and their relation with neurologic and
      psychopathologic symptoms is loose. The pattern of neuropsychologic impairment
      accentuates psychomotor slowing combined with memory disturbances, and resembles
      features observed in subcortical cognitive impairment.

PMID- 10949528
TI  - Soluble L-selectin levels in serum and cerebrospinal fluid in patients with
      multiple sclerosis and systemic lupus erythematosus.
AB  - Soluble L-selectin (sL-selectin) concentrations were measured in paired samples
      of serum and cerebrospinal fluid by an ELISA method. Patients with several forms
      of multiple sclerosis (MS) and systemic lupus erythematosus with central nervous
      system involvement (SLE-CNS) were investigated. Elevated CSF sL-selectin
      concentrations were found in patients with SLE-CNS (7.62 +/- 3.31 ng/ml) and with
      relapsing-remitting form of MS (6.99 +/- 4.72 ng/ml) compared to the control
      group (4.00 +/- 0.95 ng/ml). The data presented suggest some similarities between
      inflammatory/immunological events in the central nervous system in patients with
      SLE-CNS and relapsing-remitting form of MS. Immunological heterogeneity in MS is
      suspected.

PMID- 10949530
TI  - A clustering of unfavourable common genetic mutations in stroke cases.
AB  - OBJECTIVES: The aetiological role of common genetic mutations was analysed in a
      subgroup of stroke patients. MATERIAL AND METHODS: A total of 406 patients were
      examined because of ischaemic stroke. After a detailed clinical scrutiny, 5 were
      found who did not exhibit any of the classical clinical risk factors. In this
      clinically homogeneous subgroup of stroke patients, the prothrombin A20210G, Hong
      Kong, Cambridge and methylenetetrahydrofolate reductase C677T (MTHFR C677T)
      mutations, angiotensin-converting enzyme polymorphism (ACE polymorphism) and
      apolipoprotein E (APO E) genotype were examined. RESULTS: In all 5 patients, the
      same type of clustering of three mutations was manifested. A heterozygous Leiden
      V mutation was observed in all 5 subjects, while a heterozygous MTHFR C677T
      mutation and an I/D genotype for ACE polymorphism were detected in 4 of them, and
      a homozygous D/D genotype and a homozygous MTHFR C677T mutation in 1. This type
      of clustering of the mutations was not observed in the remaining 401 stroke
      patients. CONCLUSION: These results suggest that the Leiden mutation might
      possibly be an aetiological factor for stroke in a rare subgroup of patients who
      do not display any of the classical risk factors. The roles of ACE D polymorphism
      and the MTHFR C677T mutation in stroke, should also be taken into consideration
      in this subgroup of stroke patients. These unfavourable genetic factors might be
      aetiological factors if they are clustered together in a stroke patient not
      presenting any of the standard clinical risk factors.

PMID- 10949531
TI  - Clinical factors associated with post-ictal headache in patients with epilepsy.
AB  - OBJECTIVES: To determine the incidence of post-ictal headaches (PIH) and clinical
      risk factors associated with the occurrence of PIH in patients with localization
      related epilepsy. MATERIALS AND METHODS: The subjects were 77 patients with
      temporal lobe epilepsy (TLE), 34 patients with occipital lobe epilepsy (OLE), and
      50 patients with frontal lobe epilepsy (FLE). The subjects were directly asked
      whether headaches occurred just after seizures. Medical charts were reviewed to
      ascertain the clinical characteristics of epilepsy in these patients. RESULTS:
      The incidence of PIH was 23% for TLE, 62% for OLE, and 42%, for FLE. The risk of
      PIH was significantly higher for OLE than for TLE or FLE, and for patients with
      generalized tonic-clonic seizures. Younger age at onset of epilepsy was also a
      risk factor for PIH. CONCLUSION: The occurrence of PIH may be related to the
      region of epileptic focus and the region of spread of epileptic discharges.

PMID- 10949532
TI  - Is Campylobacter lipopolysaccharide bearing a GD3 epitope essential for the
      pathogenesis of Guillain-Barre syndrome?
AB  - The hypothesis has been proposed that the GD3 ganglioside-like lipopolysaccharide
      (LPS) is essential for and functions in the development of Guillain-Barre
      syndrome (GBS) and Miller Fisher syndrome (MFS) subsequent to Campylobacter
      jejuni enteritis. Our study showed that patients with GBS or MFS who had
      previously suffered diarrhea had anti-GD3 antibodies less often than those who
      had not had diarrhea. Sera from patients who showed GBS or MFS with the serologic
      evidence of prior C. jejuni infection had anti-GD3 antibodies less frequently
      than sera from those without evidence of infection. Statistical analysis showed
      that anti-GD3 antibodies were less frequent in patients with GBS or MFS from whom
      C. jejuni had been isolated than were other antiganglioside antibodies, such as
      anti-GM1 antibodies. These results could not support the above hypothesis.

PMID- 10949533
TI  - Correlation of neurological manifestations and MR images in a patient with
      Wilson's disease after liver transplantation.
AB  - Orthotopic liver transplantation (OLT) has been applied to patients with Wilson's
      disease (WD) for correction of irreversible liver cirrhosis. However, the
      neurological outcome and the correlation between clinical manifestations and
      neuroimage findings after OLT remain uncertain. We present a WD patient who
      showed an improvement in both liver functions and neurological manifestations
      after OLT. Serum levels of ceruloplasmin and copper returned to normal rapidly
      after the operation. His ataxic gait was improved 5 months later and dysmetria
      and tremor disappeared 11 months later. The high signal intensities on T2
      weighted brain magnetic resonance images regressed at bilateral thalami 5 months
      later and disappeared in bilateral thalami and red nuclei 16 months after OLT. We
      conclude that the neurological improvement could be expected in WD patients after
      OLT. The improvement was correlated with the MRI changes in red nuclei and
      bilateral thalami.

PMID- 10949534
TI  - Phase-shifting effects of light on the circadian rhythms of 5-methoxytryptophol
      and melatonin in the chick pineal gland.
AB  - In the chick pineal gland, 5-methoxytryptophol and melatonin concentrations
      fluctuate in a rhythmic manner. These rhythms are circadian in nature persisting
      in constant darkness and have opposite phases. Acute exposure of chicks to white
      light (30 lux for 5, 10, 20, and 30 min) at night increased the amount of pineal
      5-methoxytryptophol and decreased pineal melatonin content. A 6 hr pulse of light
      (100 lux) applied early in the subjective night (CT12-CT18) caused a delay in the
      phase of the circadian rhythms of 5-methoxytryptophol and melatonin by 3.7 and
      4.5 h, respectively, compared to untreated controls. When the 6 hr light pulse
      was given during the late subjective night (C18 CT24) it advanced the phase of
      the 5-methoxytryptophol and melatonin rhythms by 8.1 and 11.9 h, respectively. In
      the chick pineal the phase-advancing effects of light on the circadian rhythms of
      5-methoxytryptophol and melatonin were more pronounced than the phase-delaying
      effects. Our results provide the first evidence that light is capable of phase
      shifting the 5-methoxytryptophol rhythm in a manner similar to its action on the
      melatonin rhythm.

PMID- 10949535
TI  - PKC activation by melatonin modulates vimentin intermediate filament organization
      in N1E-115 cells.
AB  - Melatonin enters cells and causes cytoskeletal rearrangements in unicellular
      organisms, plants and vertebrates. This pineal secretory product causes
      microtubule enlargement and neurite outgrowth by a calmodulin antagonism in N1E
      115 cells. Recently, direct in vitro activation of protein kinase C by melatonin
      was described. Vimentin intermediate filaments are attached to microtubules and
      their organization depends on both microtubule distribution and phosphorylation
      of specific proteins. Protein kinase C is a serine threonine kinase which
      phosphorylates vimentin and through this mechanism causes intermediate filament
      disassembly. In this work the effects of melatonin on protein kinase C
      activation, content, and subcellular distribution were studied in N1E-115 cells.
      Also, melatonin effects on vimentin phosphorylation and subcellular distribution
      were explored. The results show that melatonin both activates and increases
      protein kinase C content in the membrane cytoskeletal fraction. Melatonin protein
      kinase C activation was followed by an increase in both vimentin phosphorylation
      and by vimentin subcellular redistribution. Moreover, staurosporine, a serine
      threonine kinase inhibitor, prevented increased vimentin phosphorylation elicited
      by melatonin. Similar effects to those caused by melatonin were obtained with the
      protein kinase C activator phorbol 12-myristate 13-acetate. Data support the idea
      that melatonin modulates vimentin organization through protein kinase C
      activation.

PMID- 10949536
TI  - Protective effect of melatonin against alpha-naphthylisothiocyanate-induced liver
      injury in rats.
AB  - The protective effect of melatonin against alpha-naphthylisothiocyanate (ANIT)
      induced liver injury with cholestasis was examined in rats injected once with the
      toxicant (75 mg/kg body weight (BW)). In rats injected with ANIT alone, liver
      injury with cholestasis did not occur 12 hr after the injection but appeared at
      24 hr, judging from the serum levels of marker enzymes and components. When
      melatonin (10 or 100 mg/kg BW) was orally administered to the ANIT-injected rats
      at 12 hr after the injection, the administered indoleamine dose-dependently
      prevented the formation of liver injury with cholestasis. In rats injected with
      ANIT alone, serum lipid peroxide (LPO) concentration increased 24 hr after the
      injection, while liver LPO concentration increased 12 hr after the injection and
      further increased at 24 hr. Myeloperoxidase (MPO) activity, an index of tissue
      neutrophil infiltration, in the liver of the ANIT-injected rats increased 12 hr
      after the injection and further increased at 24 hr. The oral administration of
      melatonin (10 or 100 mg/kg BW) to the ANIT-injected rats attenuated the increases
      in serum and liver LPO concentrations and liver MPO activity found at 24 hr after
      the injection in a dose-dependent manner. These results indicate that orally
      administered melatonin at pharmacological doses protects against ANIT-induced
      liver injury with cholestasis in rats, and suggest that this protective effect of
      melatonin could be due to its antioxidant action and its inhibitory action
      against neutrophil infiltration in the liver of ANIT-injected rats.

PMID- 10949537
TI  - Antisense experiments reveal molecular details on mechanisms of ICER suppressing
      cAMP-inducible genes in rat pinealocytes.
AB  - In the rat pineal gland neuronal signals determine the rhythmic synthesis of the
      hormone melatonin. Norepinephrine (NE) is the principal neurotransmitter that
      drives hormone synthesis by activating the cAMP signaling pathway. This
      activation depends on transcriptional and posttranscriptional regulatory
      mechanisms. The cAMP-dependent transcriptional regulation of the rate-limiting
      enzyme of melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT)
      involves the activating transcription factor (TF) CREB and the inhibitory TF
      ICER. By silencing elements of this cAMP-dependent neuroendocrine transduction
      cascade we wished to gain further insight into the role of ICER in the regulation
      of gene expression in rat pineal gland. Inhibition of specific kinases in primary
      pinealocyte cultures showed that ICER induction depends pivotally on the
      activation of cAMP-dependent protein kinase II. Eliminating ICER's impact by
      transfecting antisense constructs into pinealocytes revealed a predominant beta
      adrenergic mechanism in regulating a cotransfected CRE-inducible reporter gene
      and notably, also the endogenous AA-NAT gene. Deciphering molecular details of
      the cAMP-dependent gene expression in mammalian pinealocytes provides a basis for
      understanding the general architecture of this signaling pathway that serves
      adaptive processes ubiquitously in the organism.

PMID- 10949538
TI  - Clinical trials of controlled-release melatonin in children with sleep-wake cycle
      disorders.
AB  - This is the first study to examine effective doses of controlled-release (CR)
      melatonin in children with chronic sleep wake cycle disorders. All 42 subjects
      had severe neurodevelopmental difficulties. Initially, a randomized double
      blinded cross-over design was used in 16 children, comparing the effectiveness of
      fast-release (FR) and CR melatonin. In the remainder of the patients, the CR
      melatonin was studied on a clinical basis. The effectiveness of treatment was
      assessed by sleep charts and clinical follow-up. Emphasis was placed on the
      judgement of the parents, who had guidance from the physicians. The average final
      CR melatonin dose in the 42 patients was 5.7 mg (2-12 mg). The studies showed
      that the FR melatonin was most effective when there was only delayed sleep onset,
      but CR formulations were more useful for sleep maintenance. Children appeared to
      require higher doses than adults.

PMID- 10949539
TI  - Protective effect of melatonin against the 1-methyl-4-phenylpyridinium-induced
      inhibition of complex I of the mitochondrial respiratory chain.
AB  - In the present study, a novel property of melatonin is shown: a protective effect
      of melatonin on the respiratory chain in isolated rat liver mitochondria and in
      striatal synaptosomes treated with 1-methyl-4-phenylpyridinium ion (MPP+). The
      cellular damage caused by MPP+, a compound that produces a Parkinsonian-like
      syndrome in humans, is the result of the mitochondrial respiration inhibition at
      the Complex I level and oxidative stress induction. Treatment of mitochondria
      with MPP+ inhibits the respiration rate. This effect was prevented by the
      inclusion of melatonin in the incubation mixture. This preventive effect, which
      is not related to the antioxidative properties of melatonin, seems to be due to
      the fact that melatonin prevents MPP+ interaction with Complex I. These results
      suggest that melatonin may protect against the effect of several Parkinsonogenic
      compounds that are associated with progressive impairment of mitochondrial
      function and increased oxidative damage.

PMID- 10949540
TI  - Effect of clonidine on plasma ACTH, cortisol and melatonin in children.
AB  - An interaction between melatonin and adrenocorticotropin (ACTH) seems to occur in
      humans and both hormones respond to beta-adrenergic stimulation. As in lower
      animal species, human pineal gland also contains alpha2-adrenergic receptors as
      does the hypothalamus-pituitary axis. In this study the response of the pineal
      gland and of the hypothalamus-pituitary-adrenal axis to alpha2-adrenergic
      stimulation was assessed. Twenty-nine children (21 males, mean age 11.2 +/- 0.6
      yr and eight females, mean age 9.1 +/- 1.1 yr) from the University of Granada
      Hospital were studied. The children were diagnosed as having growth problems but
      with a normal response of growth hormone (GH) to clonidine test. Changes in
      plasma levels of ACTH, cortisol and melatonin were evaluated in these children
      after oral administration of the alpha2-adrenoceptor agonist clonidine (100
      microg/m2) or a placebo. Plasma ACTH, cortisol and melatonin were measured before
      (basal) and at 30, 60 and 90 min after oral clonidine or placebo administration.
      Hormonal determinations were carried out by commercial radioimmunoassay kits,
      previously standardised in our laboratory. The results show a significant
      decrease in plasma ACTH, cortisol and melatonin 30 min after clonidine
      administration (P < 0.001), reaching lowest values at 90 min after the drug was
      administered. The reduction in the levels of these hormones is independent of
      their normal circadian decay since the control group showed a significantly
      different pattern of behaviour. These data support the existence of an inhibitory
      alpha2-adrenergic influence on both the pineal gland and the hypothalamus
      pituitary-adrenal in children and further support the presence of alpha2
      adrenoceptors in the human pineal gland.

PMID- 10949541
TI  - Increased levels of oxidatively damaged DNA induced by chromium(III) and H2O2:
      protection by melatonin and related molecules.
AB  - Chromium (Cr) compounds are known occupational and environmental carcinogens.
      This trace element is found in the workplace primarily in the valence forms
      Cr(III) and Cr(VI). Cr(III), which was thought originally to be relatively
      nontoxic, was recently found to be more reactive toward purified DNA than was
      chromium(VI). Herein, we examined the ability of Cr(III) to induce oxidative DNA
      damage by measuring the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in
      purified calf thymus DNA incubated with CrCl3 plus H2O2. In this system we
      observed that the Cr(III)-induced formation of 8-OH-dG in isolated DNA was both
      dose- and time-dependent. When melatonin and related molecules, including 6
      methoxy-1,2,3,4-tetrahydro-beta-carboline (pinoline), N-acetylserotonin, 6
      hydroxymelatonin and indole-3-propionic acid, were co-incubated with CrCl3 plus
      H2O2, the accumulations of 8-OH-dG in DNA samples were markedly inhibited in a
      concentration-dependent manner. The concentrations of each indole required to
      reduce DNA damage by 50%, i.e. the IC50 values, were 0.48, 0.51, 0.88, 1.00 and
      3.08 microM for pinoline, melatonin, N-acetylserotonin, 6-hydroxymelatonin and
      indole-3-propionic acid, respectively. These results suggest that one of the
      mechanisms by which Cr(III) may induce cancer is via Fenton-type reactions which
      generate the hydroxyl radical (*OH). The findings also indicate that the
      protective effects of melatonin and related molecules against Cr(III)-induced
      carcinogenesis relate to their direct *OH scavenging ability which thereby
      reduces the formation of the damaged DNA product, 8-OH-dG.

PMID- 10949542
TI  - Bright light imagery does not suppress melatonin.

PMID- 10949543
TI  - Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within
      the cadherin superfamily.
AB  - Desmoglein 3 is a cadherin-like calcium-dependent cell adhesion molecule
      expressed primarily in suprabasal keratinocytes of the epidermis. In this study,
      we have cloned the full-length cDNA and characterized the entire gene structure
      for the mouse desmoglein 3 gene (Dsg3). Isolation of overlapping cDNA clones,
      together with 5' and 3' rapid amplification of cDNA ends (RACE), allowed
      delineation of the entire coding sequence. The transcriptional initiation site
      was confirmed by primer extension and reverse transcription polymerase chain
      reaction analysis. The entire cDNA consisted of 6407 bp with an open reading
      frame of 2979 bp, and the deduced polypeptide contained 993 amino acids.
      Comparison of mouse and human desmoglein 3 amino acid sequences demonstrated
      85.6% homology. Computer analysis suggested the presence of a transmembrane
      segment, 5 potential calcium binding sites, and a RAL motif which corresponds to
      the HAV motif, the potential site for homophilic interaction of typical
      cadherins. The mouse desmoglein 3 gene consisted of 15 exons in chromosome 18.
      Comparison of the intron-exon organization of Dsg3 with various cadherins from
      different species revealed remarkable conservation. This relatively high level of
      conservation both at the protein and genomic level suggests that desmoglein 3
      plays an important role in keratinocyte cell-cell adhesion.

PMID- 10949544
TI  - Solar-simulating irradiation of the skin of human subjects in vivo produces
      Langerhans cell responses distinct from irradiation ex vivo and in vitro.
AB  - It has been postulated that Langerhans cells (LC) provide tolerogenic signals in
      the local impairment of cutaneous immune functions and antigen-specific tolerance
      induced by UV radiation. Studies in vitro and ex vivo have indicated that UV
      radiation may down-regulate the expression of costimulatory molecules on LC,
      leading to reduced antigen-presenting function. In contrast, we recently observed
      an up-regulatory stage in the number of human epidermal LC with induced
      expression of B7 costimulatory molecules 12-24 h after solar-simulating UV
      radiation (SSR) in vivo. To examine the apparent discrepancy between the observed
      human LC responses in vitro, ex vivo and in vivo, we compared the three protocols
      in a parallel fashion. The intact skin as well as skin explants and epidermal
      cell suspensions from the same individuals were irradiated with a single
      erythematogenic dose of SSR. The expression of cell surface markers in the
      epidermal cells was analysed with flow cytometry 24 h later. The number of
      CD1a+/HLA-DR+ LC increased post-SSR in vivo by a factor of 2.8+/-0.4, whereas in
      irradiated skin explants ex vivo or in cell suspensions in vitro, reduced numbers
      were seen. HLA-DR expression intensities were found to have increased on DR+ and
      CD1a+/DR+ cells in vivo. Similarly, SSR induced B7-2 (CD86) expression in CD1a+
      cells significantly in vivo (P=0.031) but reduced the expression ex vivo or in
      vitro. We conclude that the early up-regulatory stage of human LC number and
      membrane markers, recorded at 24 h after a single exposure to SSR, is exclusively
      an in vivo phenomenon.

PMID- 10949545
TI  - IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent
      increase in mycosis fungoides progression.
AB  - Cytokines are of major importance for the pathogenesis of cutaneous T-cell
      lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth
      factors for the malignant T cells in these entities. To investigate the
      expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T
      cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing
      skin biopsies from CTCL patients at different stages in comparison to psoriatic
      and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL
      entities. Remarkably, there was some evidence for a stage-dependent increase
      during MF progression. We found only slight overexpression in early stage MF,
      when only few tumor cells are detectable within the infiltrates, whereas marked
      overexpression was found in more advanced lesions, which are characterized by a
      higher density of malignant cells. These results suggested that CTCL cells
      themselves might produce the cytokines. To further elucidate this hypothesis, two
      CTCL cell lines were analyzed but gave conflicting results. Therefore, the
      cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear.
      Considering the significant overexpression of IL-15 and IL-16 and their
      biological capacities it is likely that these cytokines contribute to the tumor
      development. So, they might be involved in growth and skin homing of CTCL cells.

PMID- 10949547
TI  - Alterations in mast cells showing tryptase and chymase activity in
      epithelializating and chronic wounds.
AB  - Mast cells can be found in contact with epidermis in certain circumstances;
      especially in chronic inflammatory skin diseases and chronic ulcers, but the
      significance of this association is obscure. In this study, the association of
      mast cells with wound healing was studied by counting mast cells in the wound
      edges at different stages after wounding the donor site skin for pinch-grafting.
      Chronic venous leg ulcers were biopsed for comparison. Tryptase- and chymase
      positive mast cells were stained enzyme-histochemically for active proteinases.
      Both the number of tryptase-positive, i.e. total mast cells, and chymase-positive
      mast cells decreased during wound healing, but only the change in chymase
      positive mast cells was statistically significant (P< or =0.03) the maximal
      decrease being 63% on day 7. No mast cells could be found in the vicinity of
      epithelialization margin. In venous leg ulcers, significantly more mast cells
      were present in the perilesional skin near the epithelium margin than in the
      wound bed (P=0.03), and mast cells were also seen in close contact with the
      basement membrane. Immunoreactivity for IL-4 and TNF-alpha in mast cells was
      studied to see if either of these molecules was associated with wound healing. In
      normally healing wounds, only a minority of mast cells were immunoreactive for
      these cytokines and no change in positive mast cell numbers could be seen during
      wound healing. In chronic wounds, IL-4 was absent in mast cells, and TNF-alpha
      positive mast cells were present only in perilesional skin and in small numbers.
      These results show that mast cells especially chymase-positive - decrease in
      number and can not be found in the epithelialization zone in normal wound
      healing, whereas tryptase-positive mast cells are associated with delayed wound
      healing and epithelialization in chronic wounds. Thus it seems, that mast cells
      attempt to control hyperproliferation of epidermis in chronic wounds.

PMID- 10949546
TI  - Use of enhanced green fluorescent protein to monitor retroviral-mediated gene
      therapy in human keratinocytes.
AB  - Keratinocytes have great promise as targets for gene therapy involving both skin
      as well as for systemic disorders due to their availability and potential long
      life span. Improvement of gene transfer into keratinocytes will be greatly
      facilitated by markers that will allow both rapid detection and efficient
      selection of transduced cells. For these purposes, a recombinant version of the
      Aequorea victoria green fluorescent protein that is enhanced for high-level
      expression in mammalian cells (EGFP) was placed into a replication-deficient
      retroviral vector. High-titer retrovirus was used to transduce both primary
      cultures of neonatal foreskin-derived human keratinocytes (HK) as well as the
      immortalized keratinocyte-derived cell line HaCaT. Both cell types stably
      expressed the EGFP, and this marker allowed rapid purification of transduced
      cells by fluorescence-activated cell sorting. EGFP expression was seen in HaCaT
      keratinocytes for at least 40 passages, and the presence of this construct did
      not effect cell growth, or apoptosis in response to UVB or etoposide. Transduced
      populations of HK were grafted into SCID mice, resulting in a functional
      epidermis. EGFP expression was readily seen in vivo by exposing the xenografts to
      an ultraviolet light source. These studies demonstrate the feasibility of using
      EGFP as a convenient and rapid marker to monitor keratinocyte gene transfer both
      in vitro and in vivo.

PMID- 10949548
TI  - Flow-cytometric characterization of normal versus psoriatic epidermis using
      improved cell separation methodology.
AB  - Recently a new approach for epidermal cell characterization was developed: three
      parameter flow cytometrical analysis of pure and complete epidermal cell
      suspensions prepared from punch biopsies followed by dermoepidermal separation by
      thermolysin. The aim of the present communication is the comparison between
      psoriatic lesional skin and normal skin using this new approach with respect to
      the percentage of suprabasal keratinocytes (keratin 10+ cells), mesenchymal
      cells, including the infiltrate cells (vimentin+ cells) and the percentage of
      basal cells in SG2 M phase, in order to validate this methodology in studies on
      psoriatic skin. Punch biopsies were taken from 7 healthy volunteers and in 7
      psoriatic patients 4 biopsies were taken in each of them from comparable lesions.
      The present study reconfirmed that the percentage of basal keratinocytes in
      psoriasis was increased and the percentage of keratin 10+ cells was substantially
      decreased as compared to normal skin. The new methodology revealed data with a
      narrow range. In psoriatic lesional skin the intra individual variation was less
      compared to the inter individual variation.

PMID- 10949549
TI  - Bovine gingival lysate: a novel substrate for rapid diagnosis of autoimmune
      vesiculo-bullous diseases. A preliminary observation.
AB  - Immunoblot assays have been developed to characterize the autoantigens and to
      detect autoantibodies in muco-cutaneous autoimmune vesiculo-bullous diseases
      using different substrates. However the results have been inconsistent, because
      availability and standardization of different substrates has been a major
      problem. The aim of this study was to develop an immunoblot assay using bovine
      gingival lysate as substrate because it is easily and readily available as well
      as inexpensive. Sera from patients with different vesiculo-bullous diseases were
      studied. These included 25 patients with pemphigus vulgaris (PV), 8 with
      paraneoplastic pemphigus (PNP), 12 with pemphigus foliaceus (PF), 25 with bullous
      pemphigoid (BP), and 22 with cicatricial pemphigoid (CP). Serum samples from 40
      normal human volunteers were also studied. The autoantibody titers were
      determined based on the binding pattern of each disease and compared to those
      obtained by routine indirect immunofluorescence (IIF). Our observations suggest
      that the titers from immunoblot assays were significantly higher than titers
      obtained by IIF (P<0.0001). When the autoantibody titers were compared using
      bovine gingival lysate and human epidermal lysate as substrate, statistically
      significant differences were not observed. The use of bovine gingival lysate as a
      substrate will facilitate the rapid and early serological diagnosis of patients
      with vesiculobullous diseases. It may also be of benefit to laboratory
      investigators studying these autoantibodies.

PMID- 10949551
TI  - Expression of nerve growth factor mRNA and its translation products in the anagen
      hair follicle.
AB  - The cellular localization of NGF mRNA and its translation products have been
      identified in ovine hair follicles. NGF mRNA was detected in the proliferating
      cells of the follicle bulb and differentiating cells of the suprabulbar region,
      but was absent from the outer root sheath. Western analysis revealed the presence
      of a 73 kDa NGF prohormone in extracts of ovine flank skin, but the mature 13 kDa
      NGF was absent. Immunohistochemical analysis with antibodies specific to mouse
      NGF and a pro-NGF specific domain localized the NGF prohormone to outer root
      sheath cells in the upper bulb region of the follicle, adjacent to the zone of
      keratinization. Antibody binding was also associated with the luminal epithelium
      of the apocrine sweat gland and the pilary canal of the follicle at its junction
      with the epidermis. These observations, together with the reported presence of
      high- and low-affinity NGF receptors in the follicle, implicate the NGF
      prohormone-responsive neuronal system in the regulation of hair growth.

PMID- 10949550
TI  - TCR Vbeta expression in the small bowel of patients with dermatitis herpetiformis
      and gluten sensitive enteropathy. Limited expression in dermatitis herpetiformis
      and treated asymptomatic gluten sensitive enteropathy.
AB  - Dermatitis herpetiformis (DH) is a blistering skin disease characterized by
      cutaneous deposits of IgA and an associated, most often asymptomatic, gluten
      sensitive enteropathy (GSE). Gluten sensitive enteropathy is also seen in
      patients that do not have skin disease or cutaneous IgA deposits, but do have
      significant gastrointestinal (GI) complaints. Patients with DH and with GSE
      without skin disease have similar small bowel morphologic changes and HLA
      associations and both the skin disease and the GI symptoms can be controlled by a
      gluten free diet. It is not known what factors allow almost all patients with DH
      to continue to eat gluten and not develop symptomatic gastrointestinal disease.
      We have examined the expression of the Vbeta T-cell receptor (TCR) in the small
      bowel of patients with DH (n=11) and of patients with both symptomatic (n=10) and
      asymptomatic (n=7) GSE without skin disease to determine if differences in the
      pattern of TCR Vbeta expression are associated with differences in the clinical
      manifestations of these diseases. TCR Vbeta expression was analyzed using RT-PCR
      from small bowel biopsies. Patients with DH and those with GSE without skin
      disease that were on a gluten free diet and asymptomatic were found to express
      6.6 and 5.6 out of 20 Vbeta families respectively, with no single family
      preference. Examination of peripheral blood lymphocytes from these patients did
      not reveal any restriction of TCR Vbeta family expression. In contrast, patients
      with symptomatic GSE expressed 12.6 Vbeta families (P< 0.05), with no consistent
      preferential expression of any single Vbeta family between patients. Patients
      with DH, who are continuing to ingest wheat, show a more restricted pattern of
      TCR Vbeta utilization, similar to that of treated patients with GSE without skin
      disease, and significantly different from GSE without skin disease patients
      eating gluten. These findings suggest that the restricted nature of the TCR Vbeta
      expression may play a role in the different clinical manifestations of dermatitis
      herpetiformis and isolated gluten sensitive enteropathy.

PMID- 10949552
TI  - Preimplantation genetic diagnosis in two families at risk for recurrence of
      Herlitz junctional epidermolysis bullosa.
AB  - The Herlitz type of junctional epidermolysis bullosa (H-JEB) is a severe
      inherited bullous disease which leads to the early demise of the affected
      newborn. Mutations in the genes encoding the 3 polypeptides of the anchoring
      filament protein laminin 5 underlie this condition. We studied 2 families with
      affected children who previously died from H-JEB. Mutation screening using
      heteroduplex analysis and direct sequencing of the PCR products revealed a
      previously described hotspot mutation in LAMB3 (R635X), and a novel delayed
      termination codon in LAMB3 in the first proband. In the second proband, we found
      a novel initiation codon mutation in LAMB3, and a novel 2 bp deletion in LAMB3.
      For preimplantation genetic diagnosis (PGD) in these families, we developed
      nested multiplex PCR assays, amplifying the mutations and informative intragenic
      polymorphisms in the probands. Single embryonic cells were biopsied from 8-cell
      embryos using standard techniques, and subjected to the multiplex PCR assay
      followed by restriction enzyme digestion. Embryos found not to carry either
      mutation were transferred to the mothers, and a pregnancy was established in the
      second family as evidenced by the elevated level of HCG, although the pregnancy
      did not persist. This study illustrates the feasibility of PGD for an inherited
      skin disorder for the first time.

PMID- 10949553
TI  - Transgene expression in human epidermal keratinocytes: cell cycle arrest of
      productively transfected cells.
AB  - We have analysed the consequences of liposome mediated gene transfer into human
      primary epidermal keratinocytes and compared non-Epstein-Barr Virus (EBV) and EBV
      based expression vectors that carry the genes encoding human Growth Hormone (hGH)
      or Enhanced Green Fluorescent Protein (EGFP). Different kinetics between the non
      EBV and EBV based vectors were revealed upon subcultivation of hGH transfected
      keratinocytes. The keratinocytes transfected with non-EBV based vector showed a
      rapid reduction in hGH production. Although the EBV based vector resulted in more
      stable expression, this was also reduced over time. Chromatin inactivation by
      deacetylation was investigated by treatment with sodium butyrate and found not to
      be the reason for the decreasing expression. Keratinocytes divided into
      subpopulations enriched for either stem cells or transit amplifying cells, based
      on beta1-integrin expression and function, do not differ significantly with
      respect to susceptibility to productive transfection. However, when the
      keratinocytes were transfected with the EGFP gene and sorted live by FACS into
      EGFP negative and positive populations, only the negative cells were capable of
      forming significant numbers of colonies. This is consistent with the observation
      that the ability to incorporate BrdU was dramatically reduced in the EGFP
      expressing population within 24-48 h post transfection indicating an almost
      complete cell cycle arrest. p53 levels were unaffected by the procedures, and the
      keratinocyte cell line HaCat, mutated in both p53 alleles, also shows a marked
      reduction in clonogenic potency upon transfection. There was a slight increase of
      TUNEL positive apoptotic nuclei in the positive population at early time points.
      However, the apoptotic index was still very low. When we measured the frequency
      of involucrin expressing cells, we found an increase in the productively
      transfected population over time indicating an initiation of terminal
      differentiation. In contrast to the transfected cultures, keratinocytes that were
      transduced using a retroviral vector showed no decrease in colony forming
      efficiency. In conclusion we find that transgene expressing cells from
      transfected cultures of epidermal keratinocytes undergo cell cycle arrest and
      initiate terminal differentiation by mechanisms which are independent of p53
      levels.

PMID- 10949555
TI  - The real struggle. The inequities facing women and minorities.

PMID- 10949554
TI  - Osseointegration in porous coated knee arthroplasty. The influence of component
      coating type in sheep.
AB  - Although cementless knee arthroplasty is a commonly performed procedure, to date
      very little was known about the process of osseointegration of knee arthroplasty
      components. Using a knee prosthesis that was specially designed for the sheep
      stifle joint, this process of osseointegration could be studied in vivo, together
      with its effects on clinical and functional performance, its influence on
      mechanical fixation, and its influence on component stability or migration over
      time. Additionally, the osseointegration capacity of a newly developed cast mesh
      porous coating could be examined. The rationale for this newly developed coating
      was to provide a surface texture with theoretically superior osseointegration
      capacity, by offering a larger and better controlled pore size, with higher
      ingrowth area compared to conventional bead type coatings. In summary, the
      conclusions that are drawn from this work are the following: 1. The degree of
      osseointegration of knee arthroplasty components is not correlated with clinical
      and functional performance. Knee arthroplasty components with fibrous integration
      can function as well as osseointegrated components at least during the first
      years after implantation. This explains the occasional reports in the literature
      of post mortem retrieved, well functioning knee arthroplasty components, with
      purely fibrous integration on histomorphometric analysis. 2. Fibrous integration
      of tibial knee arthroplasty components, however, leads to less mechanical
      fixation strength of these components. Osseointegrated components are much more
      strongly fixed to the underlying bone. This difference in mechanical fixation
      strength is detectable under physiologic loads. 3. Fibrous integration of tibial
      knee arthroplasty components leads to increased migration, becoming apparent
      after 1 year with radiostereometric analysis (RSA). Osseointegrated components
      are significantly more stable over time. 4. Fibrous integration is less
      desirable, since it leads to mechanically less rigidly fixed implants, and
      subsequently to migration over time. On the long-term, fibrous integration might
      therefore lead to loosening. 5. RSA is an effective tool to assess migration of
      knee arthroplasty components. The RSA migration of an uncemented component is
      also an indicator of its degree of osseointegration and its mechanical fixation
      strength, since RSA migration is correlated with these two parameters. RSA is
      therefore especially useful during the first postoperative years, since increased
      migration indicates fibrous integration and low mechanical fixation strength,
      suggesting an increased risk for subsequent loosening at a later stage. Patients
      with increased early component migration on RSA might therefore be advised to
      impose specific restrictions on their knee arthroplasty. 6. Osseointegration is
      not routinely achieved in conventional porous coated tibial knee arthroplasty
      components. The development of a theoretically superior cast mesh coating did not
      lead to a significantly higher degree of osseointegration. It is suggested that
      the lack of sufficiently small interface gaps and the lack of sufficiently small
      interface micromotion--two known prerequisites for reliable osseointegration to
      occur--are the main reasons inhibiting osseointegration, both in this animal
      model and in the human situation. 7. Significant osseointegration, however, does
      occur in the newly developed cast mesh coated components, when they are
      additionally coated with a vacuum plasma sprayed 50 microns hydroxyapatite layer.
      The newly developed cast mesh coating is ideally suited for such an additional
      hydroxyapatite coating. Remarkably high percentages of both bone ingrowth and
      ongrowth can be seen with these hydroxyapatite coated cast mesh coatings, higher
      than so far reported for current tibial knee arthroplasty components. These
      osseointegrated hydroxyapatite coated cast mesh components show significantly
      higher mechanical fixation strength and lower RSA migratio

PMID- 10949556
TI  - Double jeopardy. The health care system slights women with disabilities.

PMID- 10949558
TI  - EMLA for circumcision?

PMID- 10949559
TI  - Whitewashing our identities.

PMID- 10949560
TI  - Whitewashing our identities.

PMID- 10949561
TI  - Whitewashing our identities.

PMID- 10949562
TI  - Assaults on autonomy.

PMID- 10949563
TI  - Not a quick call.

PMID- 10949564
TI  - Continuous local anesthetics.

PMID- 10949565
TI  - New drugs, new effects, new problems.

PMID- 10949566
TI  - The HIV floor. On a student nursing rotation.

PMID- 10949567
TI  - Preventing the downward spiral.

PMID- 10949569
TI  - Emergency: preeclampsia.

PMID- 10949568
TI  - Urinary retention. Management in the acute care setting. Part. 2.

PMID- 10949570
TI  - Beyond the sound bites: election 2000. A quick guide to the candidates' positions
      on pressing health care concerns.

PMID- 10949571
TI  - Pain management. A moral imperative.

PMID- 10949572
TI  - Correspondence from abroad: when tradition maims.

PMID- 10949573
TI  - Keeping secrets secret. Legislation to secure patient privacy and confidentiality
      is still needed.

PMID- 10949574
TI  - Congressional action sought.

PMID- 10949575
TI  - The wild blue yonder. Should nurses be floating to unfamiliar units?

PMID- 10949576
TI  - Seeking the perfect fit. Alternatives to latex gloves.

PMID- 10949577
TI  - Matrix metalloproteinases in tumor invasion.
AB  - Controlled degradation of extracellular matrix (ECM) is essential for the growth,
      invasion, and metastasis of malignant tumors, and for tumor-induced angiogenesis.
      Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral
      endopeptidases collectively capable of degrading essentially all ECM components
      and they apparently play an important role in all these aspects of tumor
      development. Furthermore, recent evidence suggests that MMPs also play a role in
      tumor cell survival. In this review, we discuss the current concept concerning
      the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis
      and targeted therapeutic intervention in cancer.

PMID- 10949578
TI  - Adhesion receptors and cell invasion: mechanisms of integrin-guided degradation
      of extracellular matrix.
AB  - The integrins are a large family of heterodimeric cell adhesion receptors
      mediating cell-matrix and cell-cell adhesion. They seem to play a central role in
      cell migration and invasion and are therefore essential in processes such as
      healing of tissue injuries and the progression of human cancer. Integrins
      function in cell invasion by mediating cell movement on matrix molecules and also
      by regulating the expression of matrix-degrading enzymes, namely the matrix
      metalloproteinases. Here we review recent findings on the mechanisms by which
      integrins regulate matrix degradation. A novel, multistep model of integrin
      guided collagen degradation is proposed.

PMID- 10949579
TI  - The plasminogen activation system in tumor growth, invasion, and metastasis.
AB  - Generation of the serine proteinase plasmin from the extracellular zymogen
      plasminogen can be catalyzed by either of two other serine proteinases, the
      urokinase- and tissue-type plasminogen activators (uPA and tPA). The plasminogen
      activation system also includes the serpins PAI-1 and PAI-2, and the uPA receptor
      (uPAR). Many findings, gathered over several decades, strongly suggest an
      important and causal role for uPA-catalyzed plasmin generation in cancer cell
      invasion through the extracellular matrix. Recent evidence suggests that the uPA
      system is also involved in cancer cell-directed tissue remodeling. Moreover, the
      system also supports cell migration and invasion by plasmin-independent
      mechanisms, including multiple interactions between uPA, uPAR, PAI-1,
      extracellular matrix proteins, integrins, endocytosis receptors, and growth
      factors. These interactions seem to allow temporal and spatial reorganizations of
      the system during cell migration and a selective degradation of extracellular
      matrix proteins during invasion. The increased knowledge about the plasminogen
      activation system may allow utilization of its components as targets for anti
      invasive therapy.

PMID- 10949580
TI  - The biology of cell locomotion within three-dimensional extracellular matrix.
AB  - Cell migration in three-dimensional (3-D) extracellular matrix (ECM) is not a
      uniform event but rather comprises a modular spectrum of interdependent
      biophysical and biochemical cell functions. Haptokinetic cell migration across
      two-dimensional (2-D) surfaces consists of at least three processes: (i) the
      protrusion of the leading edge for adhesive cell-substratum interactions is
      followed by (ii) contraction of the cell body and (iii) detachment of the
      trailing edge. In cells of flattened morphology migrating slowly across 2-D
      substrate, contact-dependent clustering of adhesion receptors including integrins
      results in focal contact and stress fiber formation. While haptokinetic migration
      is predominantly a function of adhesion and deadhesion events lacking spatial
      barriers towards the advancing cell body, the biophysics of the tissues require a
      set of cellular strategies to overcome matrix resistance. Matrix barriers force
      the cells to adapt their morphology and change shape and/or enzymatically degrade
      ECM components, either by contact-dependent proteolysis or by protease secretion.
      In 3-D ECM, in contrast to 2-D substrate, the cell shape is mostly bipolar and
      the cytoskeletal organization is less stringent, frequently lacking discrete
      focal contacts and stress fibers. Morphologically large spindle-shaped cells
      (i.e., fibroblasts, endothelial cells, and many tumor cells) of high integrin
      expression and strong cytoskeletal contractility utilize integrin-dependent
      migration strategies that are coupled to the capacity to reorganize ECM. In
      contrast, a more dynamic ameboid migration type employed by smaller cells
      expressing low levels of integrins (i.e., T lymphocytes, dendritic cells, some
      tumor cells) is characterized by largely integrin-independent interaction
      strategies and flexible morphological adaptation to preformed fiber strands,
      without structurally changing matrix architecture. In tumor invasion and
      angiogenesis, migration mechanisms further comprise the migration of entire cell
      clusters or strands maintaining stringent cell-cell adhesion and communication
      while migrating. Lastly, cellular interactions, enzyme and cytokine secretion,
      and tissue remodeling provided by reactive stroma cells (i.e. fibroblasts and
      macrophages) contribute to cell migration. In conclusion, depending on the
      cellular composition and tissue context of migration, diverse cellular and
      molecular migration strategies can be developed by different cell types.

PMID- 10949581
TI  - The Ras family of GTPases in cancer cell invasion.
AB  - The ability of tumoral cells to invade surrounding tissues is a prerequisite for
      metastasis. This is the most life-threatening event of tumor progression, and so
      research is intensely focused on elucidating the mechanisms responsible for
      invasion and metastasis. The Ras superfamily of GTPases comprises several
      subfamilies of small GTP-binding proteins whose functions include the control of
      proliferation, differentiation, and apoptosis, as well as cytoskeleton
      organization. The development of metastasis is a multistep process that requires
      coordinated activation of proliferation, motility, changes in normal cell-to-cell
      and cell-to-substrate contacts, degradation of extracellular matrix, inhibition
      of apoptosis, and adaptation to an inappropriate tissue environment. Several
      members of the Ras superfamily of proteins have been implicated in these
      processes. The present review summarizes the current knowledge in this field.

PMID- 10949582
TI  - Cellular turnover and extracellular matrix remodeling in female reproductive
      tissues: functions of metalloproteinases and their inhibitors.
AB  - Female reproductive tissues possess a unique ability to accommodate a remarkable
      amount of cell turnover and extracellular matrix (ECM) remodeling following
      puberty. Cellular structures within ovary, uterus, and mammary tissue not only
      change cyclically in response to ovarian hormones but also undergo
      differentiation during pregnancy, and eventually revert to that resembling the
      pre-pregnant stage. Cell proliferation, apoptosis, invasion, and differentiation
      are integral cellular processes that are precisely regulated in reproductive
      tissues, but become dysregulated in pathologies such as cancer. Explicit
      reorganization of ECM and basement membranes is also critical to preserve the
      form and function of these tissues. Here we review the evidence that coordinated
      spatiotemporal expression patterns of matrix metalloproteinase (MMP) genes and
      their tissue inhibitors (TIMPs) are important in cell and ECM turnover of the
      ovary, uterus, and mammary tissues. We discuss how perturbation in these gene
      families may impact the biology of these reproductive tissues and the factors
      implicated in the control of MMP and TIMP gene expression. The observed trends in
      MMP and TIMP expression involved in ovarian and mammary carcinomas are also
      presented.

PMID- 10949583
TI  - Current applications of single-cell PCR.
AB  - The advent of the polymerase chain reaction (PCR) has revolutionised the way in
      which molecular biologists view their task at hand, for it is now possible to
      amplify and examine minute quantities of rare genetic material: the limit of this
      exploration being the single cell. It is especially in the field of prenatal
      diagnostics that this ability has been readily seized upon, as it has opened up
      the prospect of preimplantation genetic analysis and the use of fetal cells
      enriched from the blood of pregnant women for the assessment of single-gene
      Mendelian disorders. However, apart from diagnostic applications, single-cell PCR
      has proven to be of enormous use to basic scientists, addressing diverse
      immunological, neurological and developmental questions, where both the genome
      but also messenger RNA expression patterns were examined. Furthermore, recent
      advances, such as optimised whole genome amplification (WGA) procedures, single
      cell complementary DNA arrays and perhaps even single-cell comparative genomic
      hybridisation will ensure that the genetic analysis of single cells will become
      common practice, thereby opening up new possibilities for diagnosis and research.

PMID- 10949584
TI  - Radical catalysis of B12 enzymes: structure, mechanism, inactivation, and
      reactivation of diol and glycerol dehydratases.
AB  - Enzymatic radical catalysis is defined as a mechanism of catalysis by which
      enzymes catalyze chemically difficult reactions by utilizing the high reactivity
      of free radicals. Adenosylcobalamin (coenzyme B12) serves as a cofactor for
      enzymatic radical reactions. The recent structural analysis of adenosylcobalamin
      dependent diol dehydratase revealed that the substrate 1,2-propanediol and an
      essential potassium ion are located inside a (beta/alpha)8 barrel. Two hydroxyl
      groups of the substrate coordinate directly to the potassium ion which binds to
      the negatively charged inner part of the cavity. Cobalamin bound in the base-on
      mode covers the cavity to isolate the active site from solvent. Based on the
      three-dimensional structure and theoretical calculations, a new mechanism for
      diol dehydratase is proposed in which the potassium ion plays a direct role in
      the catalysis. The mechanisms for generation of a catalytic radical by homolysis
      of the coenzyme Co-C bond and for protection of radical intermediates from
      undesired side reactions during catalysis are discussed based on the structure.
      The reactivating factors for diol and glycerol dehydratases have been identified.
      These factors are a new type of molecular chaperone which participate in
      reactivation of the inactivated holoenzymes by mediating ATP-dependent exchange
      of the modified coenzyme for free intact coenzyme.

PMID- 10949585
TI  - The terminase enzyme from bacteriophage lambda: a DNA-packaging machine.
AB  - This review focuses on the biochemical, biophysical, and catalytic properties of
      terminase, an enzyme involved in bacteriophage lambda genome packaging. The
      holoenzyme possesses ATPase, DNA strand-separation, and site-specific nuclease
      activities that work in concert to insert a viral genome into the confines of a
      performed capsid. Moreover, the terminase subunits are part of a series of
      nucleoprotein complexes involved in genome packaging, including remarkably stable
      intermediates that transition to a highly mobile DNA packaging 'machine.' Models
      for the assembly and interconversion of these complexes are presented.
      Interactions between the catalytic sites in the enzyme complex, and modulation of
      these catalytic activities as it relates to the assembly and relative stability
      of the packaging intermediates are discussed. This ordered progression of
      nucleoprotein intermediates is a common theme in biology as demonstrated by
      mechanistic similarities between viral DNA packaging, the initiation of
      chromosomal replication, and the initiation of transcription. Terminase is thus
      part of a growing number of examples of biological 'machines' or molecular
      'motors.'

PMID- 10949586
TI  - Loperamide: novel effects on capacitative calcium influx.
AB  - Loperamide is a widely used antidiarrheal that primarily acts at nanomolar
      concentrations through activation of opioid receptors in the gastrointestinal
      tract. At somewhat higher concentrations, loperamide blocks calmodulin activity,
      calcium channels, N-methyl-D-aspartate-receptor channels, and maitotoxin-elicited
      calcium influx. Loperamide at micromolar concentrations has now been shown to
      have a remarkable stimulatory effect on the capacitative calcium influx that is
      triggered in many cells by depletion of the inositol-trisphosphate-sensitive
      stores of calcium in the endoplasmic reticulum. The mechanism whereby loperamide
      enhances levels of intracellular calcium elevated by capacitative calcium influx
      is, as yet, undefined.

PMID- 10949587
TI  - 'Classical' and 'new' diabetogens--comparison of their effects on isolated rat
      pancreatic islets in vitro.
AB  - This study compares functional and morphological alterations caused by
      application of alloxan, streptozotocin, xanthine oxidase/hypoxanthine (generation
      of reactive oxygen species), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP,
      liberation of nitric oxide) to isolated rat pancreatic islets in vitro. In
      perifusion experiments, membrane leakage--detected by non-stimulated insulin
      release--was found after application of all drugs, but showed a substance
      specific time pattern. Twenty-four hours after application of the classical
      diabetogens (alloxan or streptozotocin), potassium chloride- and glucose
      stimulated insulin secretion were markedly reduced, while a persistent reduction
      was observed neither after exposure to xanthine oxidase/hypoxanthine, nor to
      SNAP. Morphological analysis of the islets revealed that nearly all beta-cells
      were destroyed following alloxan or streptozotocin treatment, while the majority
      of beta-cells were configured regularly after application of xanthine
      oxidase/hypoxanthine or SNAP. Necrotic cells found after xanthine
      oxidase/hypoxanthine usually differed in morphology from those observed after
      application of the classical diabetogens. While the former cells were
      characterised by swollen nuclei, the latter had shrunken nuclei with irregular
      condensed chromatin. Apoptosis was found only following nitric oxide exposure.
      Due to these differences, it seems unlikely that alloxan, streptozotocin,
      xanthine oxidase/hypoxanthine, and nitrix oxide have a common major feature in
      their toxic action.

PMID- 10949588
TI  - Decreased monosaccharide transport in renal brush-border membrane vesicles of
      spontaneously hypertensive rats.
AB  - Na(+)-dependent D-glucose and D-galactose transport were studied in brush-border
      membrane vesicles (BBMVs) from kidney cortex isolated from both spontaneously
      hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto (WKY)
      rats. Initial rates and accumulation ratios of Na(+)-dependent D-glucose and D
      galactose transport were significantly lower in SHR compared with WKY, the
      observed decreases being similar for both substrates. To explain the reduction in
      sugar transport by renal BBMVs, the density of Na(+)-dependent sugar
      cotransporters was studied in BBMVs from kidney cortex isolated from SHR and WKY
      rats. Phlorizin-specific binding and Western blot analysis indicated a reduction
      in the density of the cotransporters in SHR relative to WKY rats. This reduction
      was similar to those found for the initial rates and accumulation ratios for D
      glucose and D-galactose in SHR. Na+ uptake, studied using 22Na+, was
      significantly increased in SHR, so the observed reduction in sugar transport
      could be due to disruption of the Na+ gradient between renal BBMVs in SHR.
      Furthermore, a significant decrease in the activity of Na(+)-K(+)-ATPase was
      observed in SHR. In conclusion, changes in the density of the Na(+)-dependent
      sugar cotransporter and in the Na+ gradient across the brush-border membranes
      might be involved in the observed reduction in sugar transport by renal BBMVs
      from SHR.

PMID- 10949589
TI  - Muscarinic M3 receptor subtype gene expression in the human heart.
AB  - The heart is an important target organ for cholinergic function. In this study,
      muscarinic receptor subtype(s) in the human heart were determined using reverse
      transcription-polymerase chain reaction. Our results demonstrated muscarinic
      receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts.
      Receptor autoradiography analysis using selective muscarinic ligands indicated an
      absence of M1 receptor subtype in the human heart. The level of muscarinic
      receptor binding in atria was two to three times greater than in ventricles. Our
      results suggest that muscarinic receptors in the human heart are of the M2 and M3
      subtypes. This is the first report of M3 receptors in the human myocardium.

PMID- 10949590
TI  - Hyperthermia associated with ophthalmic surgery.

PMID- 10949591
TI  - Surgery for abnormal head position in congenital nystagmus.

PMID- 10949592
TI  - The effect of age on the radiosensitivity of rat lenses.

PMID- 10949593
TI  - Behavioral and anatomical aspects of experimental amblyopia in monkeys.

PMID- 10949594
TI  - Exfoliation syndrome.

PMID- 10949595
TI  - Primary divergence insufficiency.

PMID- 10949596
TI  - Results of external trabeculotomy.

PMID- 10949597
TI  - An unusual hamartoma of the pigment epithelium and retina simulating choroidal
      melanoma and retinoblastoma.

PMID- 10949598
TI  - Congenital melanomas.

PMID- 10949599
TI  - Improvements in the diagnosis of posterior uveal melanomas.

PMID- 10949600
TI  - The fifth Frederick H. Verhoeff Lecture. The role of the lymphocyte (cell
      mediated) immunity in ocular disease.

PMID- 10949602
TI  - Antibodies and interferon--some new approaches.

PMID- 10949601
TI  - New antifungal therapy in ophthalmology.

PMID- 10949603
TI  - The changing character of infectious corneal disease: emerging opportunistic
      microbial forms (1928-1973).

PMID- 10949604
TI  - Immunologic reconstitution in a patient with keratoconjunctivitis, superficial
      candidiasis and hypoparathyroidism: the role of immunocompetent lymphocyte
      transfusion and transfer factor.

PMID- 10949605
TI  - Conjunctivo--dacryocystostomy: a modified conjunctivo--dacryocystorhinostomy.

PMID- 10949606
TI  - Meningomyelocoele--associated ocular abnormalities.

PMID- 10949607
TI  - Lateral canthal reconstruction.

PMID- 10949608
TI  - Endothelium of the human organ cultured cornea: an electron microscopic study.

PMID- 10949609
TI  - Macular pucker and peripheral retinal lesions.

PMID- 10949610
TI  - The natural history of retinal breaks without detachment.

PMID- 10949611
TI  - The biological behavior and pathological features of carcinoma metastatic to the
      eye and orbit.

PMID- 10949612
TI  - Extraocular muscle transplantation.

PMID- 10949613
TI  - Ocular pressure studies in the diagnosis of carotid artery disease.

PMID- 10949616
TI  - [Rude attacks on child psychiatrists. The scientology society attacks
      colleagues].

PMID- 10949614
TI  - Gliomas of the optic nerve and chiasm in childhood.

PMID- 10949617
TI  - [Web sites on tinnitus, fibromyalgia, chronic fatigue syndrome, etc. Here your
      patients seek information].

PMID- 10949618
TI  - [Helping patients with phantom pain. Prosthesis for the brain?. Interview by
      Dipl. Biochem. Petra Eiden].

PMID- 10949615
TI  - Adrenergic supersensitivity of the scorbutic iris.

PMID- 10949619
TI  - [Qualified experts warn of secret danger. Many lung cancer fatalities are caused
      by radon in the residence].

PMID- 10949620
TI  - [Angina pectoris: saving a lot of money with acupuncture].

PMID- 10949622
TI  - [New drugs for 1999].

PMID- 10949621
TI  - [Evaluating the information flood of this year. This was really important for
      general practice!].

PMID- 10949623
TI  - [Hypertension and cardiac arrhythmias. Beta blockers frequently help, but not
      always].

PMID- 10949624
TI  - [Reconstruction after gastrectomy. Which patient benefits from a stomach
      substitute?].

PMID- 10949625
TI  - [Modern hearing aids. From digital to implantable hearing aid].

PMID- 10949626
TI  - [Crohn disease, ulcerative colitis. When bacteria attack the intestinal
      wall....].
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are clinical entities
      characterized by spontaneous relapses and are thought to be caused in large part
      by a dysregulated immune response to inflammatory stimuli. Specific infectious
      agents or antigens inducing or perpetuating inflammation, however, are not known.
      Recent results in contrast support the hypothesis, that the normal intestinal
      flora plays a central role in the pathogenesis of both diseases. Studies
      performed with E. coli Nissle 1917 demonstrated that this bacterium can
      positively affect the course of disease in UC and CD patients. The clinical
      efficacy of probiotics can yield valuable information about disease pathogenesis
      and, as a modification of current standard therapy, opens new and interesting
      therapeutic alternatives.

PMID- 10949627
TI  - [Migraine. Clinical aspects and therapy].

PMID- 10949628
TI  - [Orientation difficulties in gastroscopy. Upside-down stomach (thoracic
      stomach)].

PMID- 10949629
TI  - [Heparin after deep venous thrombosis. Even the first injection the patient can
      administer himself].

PMID- 10949630
TI  - [A new pharmacological principle is effective--rofecoxib. Specific COX-2
      inhibition].

PMID- 10949631
TI  - [3. Diarrhea as the man symptom].

PMID- 10949632
TI  - [Dyspnea or confusion after trauma? Consider fat embolism syndrome].
AB  - Three patients, 2 women aged 26 and 19 years and a 65-year-old man, underwent
      surgical fracture treatment after a motor vehicle accident with fractures of the
      lower extremity. They developed respiratory distress from fat embolism syndrome.
      After maximal support in the ICU 2 of them died and 1 recovered. Fat embolism
      syndrome is a clinical condition mostly seen after long bone fractures. The main
      features are respiratory distress, cerebral confusion and a petechial rash.
      Usually the presentation is quite benign, but severe morbidity and even mortality
      can occur in some cases. It is caused by a combination of a mechanical and a
      biochemical pathway. Therapeutic options consist of respiratory and haemodynamic
      support. Preventive measures are rapid fracture fixating, good analgesia,
      adequate fluid infusion and tissue oxygenation.

PMID- 10949633
TI  - [Second primary tumors in patients treated at an early age for Hodgkin's disease;
      consequences for the follow-up].
AB  - As curative treatment is now available for a substantial group of cancer
      patients, it is increasingly important to evaluate how late complications of
      treatment affect their long-term survival. Two recent publications summarize the
      second malignancies in survivors of Hodgkin's disease treated during adolescence
      or young adulthood. After more than 20 years' follow-up, the risk of solid
      tumours is still much greater in survivors of Hodgkin's disease than in the
      population at large. Age at treatment has a major effect on the occurrence of
      second malignancy. Reassuringly, the increased risk of solid tumours in patients
      who were less than 20 years of age seems to decrease as these patients grow
      older. The data of these studies suggest that chemotherapy may increase the risk
      of solid tumours from radiotherapy. Special alertness to symptoms of second
      malignancies is advised during follow-up after treatment for Hodgkin's disease,
      especially in patients treated below the age of 20.

PMID- 10949634
TI  - [Added value of positron emission tomography with fluoro-18-deoxyglucose as the
      tracer (FDG-PET) in clinical problem cases in oncology].
AB  - Positron emission tomography with fluoro-18-deoxyglucose as tracer molecule (FDG
      PET) is a relatively new imaging technique used in oncology to study tumour
      metabolism in vivo. Both qualitative and quantitative data obtained by PET
      provide unique information to the clinician and may guide the therapeutic
      approach in selected patients, where conventional diagnostic tests like CT or MRI
      yield equivocal results. According to the experience obtained in the Vrije
      Universiteit Medical Centre in Amsterdam, the additional value of FDG-PET can be
      explained by the sensitivity and the specificity of the technique, combined with
      the visualization of the whole body. FDG-PET may reveal metastases and tumour
      tissue may be differentiated from scar tissue and necrosis. PET is expensive and
      its effects on patient outcome has yet to be established.

PMID- 10949635
TI  - [Roaming through the methodology. XX. Randomization as a means of avoiding
      confounding through indication].
AB  - Two methodological issues are central in discussions about the value of
      randomised studies for evaluation of the effectiveness of medical interventions:
      confounding by indication and generalizability. Confounding occurs when a factor
      with bearing on the outcome of disease, has a different distribution among
      intervention groups. Confounding by indication is a special case and results from
      the fact that in medical practice the choice between intervention alternatives is
      dependent on the perceived prognosis of the patient for whom these interventions
      are considered. As the precise arguments for this choice in general are not
      explicit and hence not measurable, correction for confounding by indication is
      impossible, and randomisation is applied. Surprisingly, systematic comparison of
      the results of randomised and non-randomised studies for the same interventions
      shows remarkable resemblance. This suggests that non-randomised studies may have
      value in specific situations, but unfortunately so far we do not know for which
      situations this may be the case.

PMID- 10949636
TI  - [CBO guideline 'Deep venous thrombosis and pulmonary embolism; revision of the
      earlier guidelines. Dutch Organization for Quality Assurance in Hospitals].
AB  - Diagnosis of clinically suspected deep venous thrombosis is based on a clinical
      score, serial compression ultrasonography and D-dimer assay. For the diagnosis of
      pulmonary embolism perfusion scintigraphy, ventilation scintigraphy, echography
      of the leg veins and pulmonary angiography in that order lead to the lowest
      mortality, morbidity and costs. Diagnostics with spiral CT followed by pulmonary
      angiography leads to equal mortality and fewer angiography procedures. Decision
      rules based on anamnesis, physical examination, blood gas analysis and chest
      radiograph have proved to be insufficiently reliable. The present D-dimer assays
      have too little sensitivity and too much variability. Thrombo-prophylaxis with
      low-molecular-weight heparin is indicated for general surgery, joint replacement
      of the knee or hip, cranial and spinal surgery, subarachnoid haemorrhage after
      surgical treatment of an aneurysm, acute myocardial infarction, ischaemic stroke
      or spinal cord lesion, intensive care patients, patients with acute paralysis due
      to a neuromuscular disorder, and bedridden patients with a risk factor.
      Prophylaxis has to be continued as long as the indication exists. In the acute
      phase of deep venous thrombosis or pulmonary embolism treatment with (low
      molecular-weight) heparin in an adequate dose is necessary. When started at the
      same time as coumarin derivatives the treatment with heparin has to be continued
      for at least 5 days. The risk of postthrombotic syndrome after deep venous
      thrombosis will be lowered by carrying compression stockings for at least 2 years
      after the event.

PMID- 10949637
TI  - [Value of the 'non-diagnostic' lung scan--further classification as to the risk
      of pulmonary embolism not reliable].
AB  - OBJECTIVE: To determine to what extent the 'non-diagnostic' lung scans made
      because of a clinical suspicion of pulmonary embolism enable further
      determination of the risk of pulmonary embolism. DESIGN: Retrospective. METHOD:
      All non-diagnostic lung perfusion ventilation scans made in the Academic Medical
      Centre of Amsterdam in 1997 of 114 patients in succession (55 males and 59
      females aged 27-85 years) were subjected to blind and independent re-evaluation
      by three observers (an experienced nuclear medicine expert, an experienced and an
      inexperienced intern) who, using a lung segment chart, estimated the risk of
      embolism as < 25%, 25-50%, 50-75% and > 75%. They did this first without and then
      with the chest X-ray. The findings were grouped on the basis of accordance or non
      accordance with the pulmonary angiogram. The interobserver agreement was
      calculated by means of kappa statistics. RESULTS: Of 58 patients the lung scan
      could be compared with a chest X-ray and a pulmonary angiogram. In 43 patients
      with a normal angiogram the observers in an average of 50% of the scans estimated
      the risk of pulmonary embolism as < 25%, as against 25-50% in 27%, 50-75% in 9%
      and > 75% in 5%. In 15 patients with a deviant pulmonary angiogram, these figures
      were 22%, 38%, 20%, and 12%, respectively. The interobserver kappa for evaluation
      without chest X-ray was < or = 0.16, as against < or = 0.41% with the chest X
      ray. CONCLUSIONS: A reliable classification of the risk of pulmonary embolism was
      not possible on the basis of non-diagnostic lung scans, regardless of whether the
      patient did or did not have pulmonary embolism. The interobserver variability was
      less when the lung scan was evaluated together with the chest X-ray, but even so
      it was unacceptably high.

PMID- 10949638
TI  - [Treatment of non-resectable liver tumors with percutaneous interstitial laser
      coagulation while interrupting blood circulation to the liver].
AB  - OBJECTIVE: To evaluate, in patients with hepatocellular carcinoma or colorectal
      carcinoma disseminated to the liver, treatment with interstitial laser
      coagulation (ILC) during temporary occlusion of vascular inflow in the liver:
      feasibility, complications and initial tumour response. DESIGN: Prospective,
      descriptive. METHODS: Patients were included if their tumours were surgically
      irresectable and smaller than 4 cm in diameter and did not exceed a number of 3.
      ILC was performed under general anaesthesia, basically via a percutaneous
      approach. Vascular inflow was occluded during laser treatment. Twenty-four hours
      after ILC a triphasic spiral CT was performed to assess the result of the
      treatment. RESULTS: In 10 patients 14 hepatic tumours were lasered in 12
      treatment sessions (10 percutaneous and 2 at laparotomy). After 5 treatment
      sessions, complications were observed of which pain at the insertion site of the
      catheters was the most frequent. For 6 out of the 10 patients with percutaneous
      procedures, discharge was within 24 hours after ILC. Nine out of the 14 tumours
      (65%) were completely coagulated. CONCLUSION: ILC with vascular inflow occlusion
      is a safe and feasible technique that can be performed during a short hospital
      stay. Initial tumour response is 65% and these results justify determination of
      duration of response in a larger group of patients.

PMID- 10949639
TI  - [Conditional discharge of three committed psychiatric patients; the ambulatory
      practice].
AB  - Three patients, two women aged 54 and 38 years and a man aged 39, of whom the
      first suffered from a schizoaffective disorder with hyperthyroidism and the
      others from schizophrenia, were admitted by virtue of the Wet Bijzondere Opneming
      in Psychiatrische Ziekenhuizen (BOPZ; Bill on Compulsory Admission to Psychiatric
      Hospitals). They were discharged under conditions of the BOPZ. The conditions
      were discussed with the patient, the psychiatric hospital, the outpatient
      department and the general practitioner. The three patients did well. This
      conditional discharge reopens the discussion on ambulatory compulsory treatment
      in the Netherlands.

PMID- 10949640
TI  - [Detailed analysis of the social costs of diabetes mellitus].

PMID- 10949641
TI  - Cerebral protection in aortic surgery.

PMID- 10949642
TI  - Ischemia and the myocardium.

PMID- 10949643
TI  - Robotically assisted endoscopic coronary artery bypass grafting: current state of
      the art.

PMID- 10949645
TI  - Surgical risk assessment.

PMID- 10949644
TI  - Transplantation for congenital heart disease.
AB  - Refinements in surgical technique, donor and recipient myocardial preservation,
      and immunosuppression have brought pediatric heart transplantation for end-stage
      heart failure (whatever the cause) from the heyday of clinical experimentation to
      the realm of a viable therapeutic. Heart transplantation in this subpopulation
      yields excellent early and midterm survival. Acute rejection remains an important
      cause of morbidity and mortality after heart transplantation in children. Future
      improvement in quality of life for these patients calls for newer
      immunosuppressive strategies to reduce acute rejection episodes and ultimately
      improve long-term graft survival.

PMID- 10949646
TI  - The electrophysiologist and the cardiac surgeon.

PMID- 10949647
TI  - Perioperative cardiac imaging.

PMID- 10949649
TI  - How to construct a monocusp valve.
AB  - Construction of a monocusp is an easy procedure that adds little, if any time to
      routine transannular patching of the right ventricular outflow tract. It also
      adds little cost to the operation when constructed from autologous pericardium.
      The monocusp's utility in preventing or lessening the impact of pulmonary
      regurgitation in the early postoperative period has been demonstrated. Its
      utility as a long-term pulmonary valve substitute will need to await longer-term
      clinical follow-up currently underway at our institution and others.

PMID- 10949648
TI  - Uncommon coagulation problems.

PMID- 10949650
TI  - Extracardiac conduit variation of the Fontan procedure.
AB  - The ECF operation is designed to improve postoperative outcome by enhancing
      factors that are critical in optimal functioning of the Fontan circulation,
      including preservation of ventricular and pulmonary vascular function, avoidance
      of dysrhythmias, and prevention of stasis and flow turbulence in the Fontan
      circuit. Preoperative strategies include an early bidirectional Glenn procedure,
      and avoiding ancillary intracardiac procedures at the time of the Fontan by
      performing them at the time of the Glenn operation. Operative strategies include
      minimizing the duration of CPB by performing the conduit to pulmonary artery
      anastomosis off bypass, using partial instead of full CPB by cannulating the IVC
      alone, avoiding hypothermia, avoiding cross-clamping of the aorta, avoiding
      atrial incisions and suture lines, using a tubular conduit to construct the
      Fontan pathway, making a large conduit to pulmonary artery anastomosis,
      incorporating the conduit into aggressive pulmonary arterioplasties, and
      offsetting of the superior and inferior cavopulmonary anastomoses.

PMID- 10949651
TI  - Angiogenesis: From the molecular to integrative pharmacology. Proceedings of the
      5th biannual meeting. Crete, Greece, July 1-7, 1999.

PMID- 10949652
TI  - Examining new models for the study of autocrine and paracrine mechanisms of
      angiogenesis through FGF2-transfected endothelial and tumour cells.
AB  - Angiogenesis is the process of generating new capillary blood vessels.
      Uncontrolled endothelial cell proliferation is observed in tumour
      neovascularization. Several growth factors and cytokines have been shown to
      stimulate endothelial cell proliferation in vitro and in vivo and among them FGF2
      was one of the first to be characterised. FGF2 is a Mr 18,000 heparin-binding
      cationic polypeptide that induces proliferation, migration, and protease
      production in endothelial cells in culture and neovascularization in vivo. FGF2
      interacts with endothelial cells through two distinct classes of receptors, the
      high affinity tyrosine-kinase receptors (FGFRs) and low affinity heparan sulfate
      proteoglycans (HSPGs) present on the cell surface and in the extracellular
      matrix. Besides experimental evidence for paracrine mode of action for FGF2, some
      observations raise the hypothesis that FGF2 may also play an autocrine role in
      endothelial cells. FGF2 may therefore represent a target for anti-angiogenic
      therapies. In order to assess the angiostatic potential of different classes of
      compounds, novel experimental models have been developed based on the autocrine
      and/or the paracrine capacity of FGF2.

PMID- 10949653
TI  - Tie-1 receptor tyrosine kinase endodomain interaction with SHP2: potential
      signalling mechanisms and roles in angiogenesis.
AB  - The endothelial receptor tyrosine kinase plays an essential role in vascular
      development where it is thought to be required for vessel maturation and
      stabilization. The ligands responsible for activating Tie-1, its signalling
      pathways and specific cellular functions are however not known. As with some
      other receptor tyrosine kinases, Tie-1 is subject to extracellular proteolytic
      cleavage generating a membrane bound receptor fragment comprising the
      intracellular and transmembrane domains. Here we examine the signalling potential
      of this Tie-1 endodomain. We show that the Tie-1 endodomain has poor ability to
      induce tyrosine phosphorylation. However, on formation the endodomain physically
      associates with a number of tyrosine phosphorylated signalling intermediates
      including the tyrosine phosphatase and adaptor protein SHP2. The assembly of this
      multimolecular complex is consistent with the endodomain having a ligand
      independent signalling role in the endothelial cell. The potential roles of
      ectodomain cleavage and cleavage activated signalling in regulating microvessel
      stability in angiogenesis, vessel remodelling and regression are considered.

PMID- 10949655
TI  - Endothelial receptor tyrosine kinases involved in blood vessel development and
      tumor angiogenesis.

PMID- 10949654
TI  - On the mechanism(s) of thrombin induced angiogenesis.
AB  - Promotion of tumour progression by thrombin is suggested by several clinical and
      laboratory observations. A plausible explanation for this effect of thrombin may
      be related to our previous findings that thrombin is a potent promoter of
      angiogenesis in the chick chorioallantoic membrane system (CAM) and in the
      Matrigel system in vivo. In this report we summarise the cellular and molecular
      actions of thrombin that could be contributing to the activation of angiogenic
      cascade. Treatment of endothelial cells with thrombin leads to activation of
      gelatinase A, which may allow for local dissolution of basement membrane, an
      essential first step of angiogenesis. Similarly thrombin-treated endothelial
      cells have diminished ability to adhere to collagen type IV and laminin. This new
      phenotype of endothelial cells can migrate and survive without attachment to
      extracellular matrix. Thrombin-treatment of endothelial cells increases the
      vectorial secretion of extracellular matrix proteins, a process essential at the
      final steps of angiogenesis. In addition, thrombin potentiates the VEGF-induced
      mitogenesis of endothelial cells. This can be explained by the upregulation of
      the VEGF receptors (KDR & flt-1) by thrombin treatment. All the aforementioned
      effects of thrombin are receptor mediated, dose-dependent and require only brief
      exposure of endothelial cells to thrombin for these actions of thrombin. The
      transduction mechanisms involved are via protein kinase C (PKC) and MAP-kinase
      pathways.

PMID- 10949656
TI  - Ontogeny of the endothelial system in the avian model.
AB  - The avian model provides an experimental approach for dissecting the origin,
      migrations and differentiation of cell lineages in early embryos. In this model,
      the endothelial network was shown to take place through two processes depending
      on the origin of endothelial precursors: vasculogenesis when angioblasts emerge
      in situ, angiogenesis when angioblasts are extrinsic. Two different mesodermal
      territories produce angioblasts, the somite which only gives rise to endothelial
      cells and the splanchnopleural mesoderm which also produces hemopoietic stem
      cells. Potentialities of the mesoderm are determined by a positive influence from
      the endoderm and a negative control from the ectoderm. The presence of
      circulating endothelial precursors in the embryonic blood stream is also
      detected.

PMID- 10949657
TI  - The role of pericytes in controlling angiogenesis in vivo.
AB  - In order to evaluate the interaction between endothelial cells and the
      perivascular pericytes during physiological angiogenesis, stereological analysis
      of fine structure was performed on samples of rat skeletal muscle where capillary
      growth was induced to a similar extent by three different interventions (indirect
      electrical stimulation, vasodilatation by alpha 1-blockade, stretch due to
      synergist extirpation). There was a significant reduction in the relative area of
      contact between pericytes and the capillary abluminal surface with stimulation,
      and withdrawal of pericyte processes coincided with an increase in anatomical
      capillary supply. These data indicate that pericytes may play an anti-angiogenic
      role in vivo in normal adult tissue similar to that proposed for in vitro models
      of angiogenesis, with their retraction during increased muscle activity possibly
      releasing endothelial cells from their contact inhibition. However, following
      long-term peripheral vasodilatation expansion of the capillary bed was
      accompanied by a co-ordinated increase in pericytes, such that coverage of
      capillaries was similar to that in control muscles. In addition, growth of
      capillaries following prolonged stretch resulted in a slightly greater increase
      in the pericyte population, suggesting they may be permissive for endothelial
      cell migration. Thus, the role of pericytes in controlling physiological
      angiogenesis is dependent on the nature of the initial stimulus, suggesting that
      in vitro data have to be interpreted with caution when discussing the mechanism
      of capillary growth in vivo.

PMID- 10949658
TI  - Insights into the vasodilation of rat retinal vessels evoked by vascular
      endothelial growth factor121 (VEGF121).

PMID- 10949659
TI  - Signal transduction and transcriptional regulation of angiogenesis.
AB  - When quiescent endothelial cells (ECs) are exposed to angiogenic factor such as
      VEGF; ECs express proteases to degrade extracellular matrices, migrate,
      proliferate and form new vessels. However, the molecular mechanism of these
      events is not fully characterized yet. We are studying the signal transduction
      and transcriptional regulation of angiogenesis. We investigated the properties of
      two VEGF receptors, Flt-1 and KDR, by using two newly developed blocking
      monoclonal antibodies (mAbs), i.e., anti-human Flt-1 mAb and anti-human KDR mAb.
      VEGF elicited induction of transcription factor Ets-1 in human umbilical vein
      endothelial cells (HUVECs). This induction was mediated by the KDR/Flt-1
      heterodimer and the KDR homodimer. The role of transcription factor Ets-1 in
      angiogenesis was further clarified. We established both high and low Ets-1
      expressing EC lines, and compared angiogenic properties of these cell lines with
      a parental murine EC line, MSS31. The growth rate was almost identical among
      three cell lines. It appeared that gene expressions of matrix metalloproteinases
      (MMP-1, MMP-3, and MMP-9) as well as integrin beta 3 were correlated with the
      level of Ets-1 expression. As a result, the invasiveness was enhanced in high Ets
      1 expressing cells and reduced in low Ets-1 expressing cells compared with
      parental cells, and high Ets-1 expressing cells made more tube-like structures in
      type 1 collagen gel. These results indicate that Ets-1 is a principle
      transcription factor converting ECs to the angiogeneic phenotype.

PMID- 10949660
TI  - Differential contribution of bradykinin receptors in angiogenesis.

PMID- 10949662
TI  - Revascularization of ischemic tissues with SIKVAV and neuropeptide Y (NPY).
AB  - Angiogenesis, the process of new vessel growth, is necessary for many normal
      physiological and pathological processes such as tumor growth, wound healing and
      ischemia. We have recently examined in vitro and in vivo the ability of two
      potent angiogenic compounds, SIKVAV (a peptide derived from the alpha chain of
      laminin-1) and Neuropeptide Y (NPY) to revascularize ischemic tissue. These
      compounds were tested in an ex vivo capillary sprouting angiogenesis assay that
      uses rat aortic rings. Both NPY and SIKVAV in the presence of VEGF, stimulated
      the formation of long sprouts at concentrations of 1 ng NPY (0.2 pmol/L) and 100
      micrograms SIKVAV. In comparison very little sprouting occurred in the control
      rings and 50 ng of VEGF alone was required to induce equivalent number of sprouts
      as NPY. SIKVAV and NPY were further tested in vivo in a rat hindlimb ischemic
      model. Both compounds (500 micrograms SIKVAV and 10 ng of NPY) were embedded in
      the rat hind limb following unilateral ligation of the femoral artery 1 cm
      proximal to the adductor hiatus. After two weeks control peptides show little or
      no revascularization of the hindlimb distal to the ligation; however, both SIKVAV
      and NPY demonstrated a two-fold increase in new vessels in the region proximal to
      the ligation. Histological sections of latex perfused hindlimb demonstrated that
      ligated limbs had very few latex-filled dermal capillaries. Limbs treated with
      SIKVAV and NPY, however, demonstrated normal distribution in the dermal capillary
      beds. These data indicate that both SIKVAV and NPY are potent angiogenic factors
      that show promising potential clinical application to the revascularization of
      ischemic tissue.

PMID- 10949661
TI  - Sensitivity of different vascular beds in the eye to neovascularization and blood
      retinal barrier breakdown in VEGF transgenic mice.
AB  - Neovascularization (NV) causes visual deficits in ocular disorders such as
      diabetic retinopathy, age-related macular degeneration, and retinopathy of
      prematurity. An understanding of the angiogenic factors promoting this abnormal
      vascular growth is necessary to devise a therapeutic approach to inhibit NV. One
      factor known to promote NV is vascular endothelial growth factor (VEGF), which
      can also induce a breakdown of the blood-retinal barrier (BRB) leading to macular
      edema, another major cause of visual loss in a variety of ocular disorders. To
      investigate the role of VEGF on ocular NV, transgenic mice have been produced
      that over-express VEGF in the photoreceptors under control of the rhodopsin
      promoter. Eyes from these mice and from littermates not expressing the transgene
      were examined using immunohistochemistry, griffonia simplicifolia isolectin-B4
      (GSA) staining to clearly visualize vessels, and electron microscopy. Levels of
      transgene expression were determined by the polymerase chain reaction. In normal
      mice, retinal vessels are organized into a superficial and a deep capillary bed
      with some vessels forming a shunt between both beds. In a transgenic line of mice
      that over-expresses VEGF (V-6), NV originates from the deep capillary bed at
      about postnatal day 10 (P10) and extends through the photoreceptor layer to form
      vascular complexes in the subretinal space with BRB breakdown occurring only in
      the area of NV. The superficial capillary bed and the choroidal vasculature are
      unaffected. In another line of transgenic mice with a higher expression rate of
      VEGF (V-24), photoreceptor degeneration begins at P7-8, soon after the onset of
      transgene expression, without widespread NV, as was observed in V-6 mice. In
      conclusion, overexpression of VEGF in transgenic mice is sufficient to cause
      retinal NV, but only the deep capillary bed is responsive. Increasing the
      expression of VEGF does not necessarily increase the amount of NV. A better
      understanding of the specific factors and conditions that result in a particular
      pattern of ocular NV may provide clues regarding the pathogenesis of ocular
      neovascular disease.

PMID- 10949663
TI  - Cellular effects and signalling pathways activated by the anti-coagulant factor,
      protein S, in vascular cells protein S cellular effects.
AB  - The anticoagulant factor protein S is a secreted vitamin K-dependent gamma
      carboxylated protein that is mainly synthesised in the liver but is also made by
      endothelial cells and megakaryocytes in culture. In previous studies we have
      shown that protein S acts as a mitogen for cultured human vascular smooth muscle
      cells. The synthesis and secretion of protein S by endothelial cells suggests
      that in addition to its role in the coagulation cascade, protein S may be an
      important autocrine factor implicated in the pathophysiology of the vascular
      system. The effects of protein S on hVSMC proliferation, migration and survival
      are discussed. The activation of the components of the MAP kinase pathway,
      ERK1/2, JNK/SAPK and p38 is also summarised. Binding and chemical cross-linking
      experiments provided evidence for the existence of a cell surface protein S
      receptor(s). By virtue of its many cellular effects, it is suggested here that
      the anticoagulant factor protein S plays an important role in the pathophysiology
      of the vasculature.

PMID- 10949664
TI  - Targeting integrins alpha v beta 3 and alpha v beta 5 for blocking tumor-induced
      angiogenesis.

PMID- 10949665
TI  - Suppression of human microvascular endothelial cell invasion and morphogenesis
      with synthetic matrixin inhibitors. Targeting angiogenesis with MMP inhibitors.
AB  - Matrix metalloproteinases (MMPs, matrixins) are a family of zinc proteinases that
      digest extracellular matrix and play a very important role in normal development
      and pathological conditions such as cardiovascular diseases and cancer
      metastasis. Type IV collagenases (gelatinase A/MMP-2 and gelatinase B/MMP-9) may
      be critical in the early steps of angiogenesis, the digestion of basement
      membrane and the migration of endothelial cells from the existing blood vessels.
      Human dermal microvascular endothelial cells were cultured on type I collagen,
      type IV collagen, and reconstituted basement membrane Matrigel and
      differentiation was examined in the presence of potent synthetic inhibitors of
      MMPs. The thiol inhibitor MAG-283 had IC50 values of 480 nM and 3 nM against
      human interstitial collagenase (MMP-1) and MMP-2, respectively, and KI value of
      2.2 nM against MMP-9. The sulfodiimine inhibitor YLL-224 had IC50 values of 180
      nM, 63 nM, and 44 nM against MMP-1, -2, and -9, respectively. These inhibitors at
      very low micromolar concentrations inhibited cell-mediated type I collagen
      degradation and partially blocked cell invasion through type IV collagen. These
      inhibitors also suppressed endothelial differentiation, i.e., formation of
      capillary-like tubes on Matrigel and on type I collagen. These results suggest
      that collagen-degrading MMPs play an important role during the initiation of
      angiogenesis.

PMID- 10949666
TI  - Tunicamycin inhibits capillary endothelial cell proliferation by inducing
      apoptosis. Targeting dolichol-pathway for generation of new anti-angiogenic
      therapeutics.
AB  - Bovine adrenal medulla microvascular endothelial cells used in this study undergo
      cellular proliferation and differentiation upon culturing in vitro as observed
      both by light and scanning electron microscopy. Cells also respond to the growth
      promoting activity of serum and basic fibroblast growth factor (FGF2). Flow
      cytometric analysis of a synchronized culture established that cells take 68
      hours to complete one cell cycle spending 36 hours in the G1 phase, 8 hours in
      the S phase, and 24 hours in the G2 + M phase when cultured in EMEM containing 2%
      heat-inactivated fetal bovine serum (FBS). At 10% serum, or in the presence of
      FGF2 (10 ng/ml-100 ng/ml) length of the cell cycle is reduced to 56 hours due to
      shortening of the G1 phase by 12 hours. Tunicamycin (a glucosamine-containing
      pyrimidine nucleotide), and an inhibitor of glucosaminyl-1-phosphate (GlcNAc 1-P)
      transferase, the first step of Glc3Man9GlcNAc2-PP-Dol (OSL) biosynthesis is found
      to inhibit the endothelial cells proliferation by inducing apoptosis as observed
      by flow cytometry and DNA laddering. Cell shrinkage, compaction of nuclei,
      membrane fragmentation, etc., typical of apoptotic response are frequently seen
      by light microscopy in the presence of tunicamycin. Scanning electron microscopy
      also exhibited a considerable amount of cell surface blebbing. Accumulation of an
      immunopositive cell specific asparagine-linked (N-linked) glycoprotein, Factor
      VIII:C in the absence of Glc3Man9GlcNAc2-PP-Dol in tunicamycin treated cells has
      been proposed as an apoptotic triggering mechanism under the current experimental
      conditions.

PMID- 10949667
TI  - The characterization of angiogenesis inhibitor from shark cartilage.
AB  - An angiogenesis inhibitor isolated from shark cartilage, SCF2, has been
      characterized. SCF2 was shown to have specific angiogenesis-inhibiting activity
      in endothelial cell culture assays. Results of structural and functional studies
      indicate that the inhibitor is not a typical protein. It is a heat-stable
      proteoglycan, which contains keratan sulfate units and peptide. Gel filtration
      chromatography shows that the molecular weight of the angiogenesis inhibitor is
      about 10 kd.

PMID- 10949668
TI  - Quantitative assays for the chick chorioallantoic membrane.
AB  - Focal application of angiogenic substances to the chick chorioallantoic membrane
      is quick and easy as a rapid screening test, but is susceptible to artefactual
      stimulation induced by carriers, hyperosmolarity, proteolytic activity, and
      indeed any cause of damage to the CAM. This can be deceptive and unanticipated.
      Focal application methods can be used for subsequent measurement by morphometry
      of the increased vascularity forming the typical spokewheel pattern of supply
      vessels. If test and control substances are applied in liquid form to the whole
      dropped CAM surface, then a much wider variety of quantitative morphometric,
      histological and biochemical techniques can be applied. Assessment of arterial
      vascularity, terminal arterial branching, supply vessels in cross-sections, and
      CAM haemoglobin content are direct measures of angiogenic effects, but are time
      consuming. Biochemical assays of collagen, protein and DNA synthesis parallel the
      other assays, and these parameters can be estimated more quickly within the
      working week. There is inherent variability in the outbred strains of hen eggs
      currently commercially available. This means that all assays require substantial
      group numbers to achieve statistical validity, generally not less than 10 eggs
      per group. The biochemical assays yield interesting time-course patterns that
      distinguish between different types of angiogenic stimulants.

PMID- 10949669
TI  - MYCN oncogene and angiogenesis: down-regulation of endothelial growth inhibitors
      in human neuroblastoma cells. Purification, structural, and functional
      characterization.
AB  - Angiogenesis, the formation of new blood vessels, is seen during embryonic
      development and tumor progression, but the mechanisms have remained unclear.
      Recent data indicate that tumor angiogenesis can be induced by cellular
      oncogenes, leading to the enhanced activity of molecules stimulating
      angiogenesis. However, activated oncogenes might also facilitate angiogenesis by
      down-regulating endogenous inhibitors of angiogenesis. We report here that
      enhanced expression of the N-myc oncogene in human neuroblastoma cells down
      regulates three inhibitors of endothelial cell proliferation. One of them was
      identified by amino acid sequencing as being identical with activin A, a
      developmentally-regulated protein. Down-regulation involves interaction of the N
      myc protein with the activin A promoter. Work is ongoing to characterize the
      other two endothelial cell inhibitors. We suggest that the N-myc induced down
      regulation of angiogenesis inhibitors could contribute to tumor angiogenesis.

PMID- 10949670
TI  - From hyperplasia to neoplasia and invasion: angiogenesis in the colorectal
      adenoma-carcinoma model.

PMID- 10949671
TI  - Tumor angiogenesis, macrophages, and cytokines.

PMID- 10949672
TI  - Microvessel density, thymidine phosphorylase expression and resistance of head
      and neck cancer to chemo-radiotherapy.

PMID- 10949673
TI  - Differential expression of angiogenic and of vascular survival factors in non
      small cell lung cancer (NSCLC).

PMID- 10949674
TI  - Thymidine phosphorylase activity in normal, hyperplastic and neoplastic
      endometrium--correlation with intratumoral angiogenesis.

PMID- 10949675
TI  - Inhibition of VEGF signal transduction. Identification of ZD4190.

PMID- 10949677
TI  - Therapeutic angiogenesis for ischemic heart disease.
AB  - The de-novo formation of vessels (angiogenesis) and the remodelling of
      preexisting collateral vessels (arteriogenesis) are processes that occur
      naturally in ischemic heart disease. Promoting these processes by administration
      of various substances or other physical stimuli (therapeutic angiogenesis) may
      provide a future strategy for the treatment of ischemic vascular diseases.
      Mechanisms of angiogenesis and arteriogenesis, as well as trials of therapeutic
      angiogenesis in animal models and humans are reviewed.

PMID- 10949676
TI  - Combretastatins novel vascular targeting drugs for improving anti-cancer therapy.
      Combretastatins and conventional therapy.
AB  - Combretastatins are a new class of compounds that appear to have anti-tumour
      activity as a result of specifically targeting the vasculature of tumours. The
      aim of this study was to investigate the potential of combretastatin A-4 disodium
      phosphate (CA4DP) to induce vascular effects in a C3H mouse mammary carcinoma,
      and to see if the anti-tumour response could be improved by combining the drug
      with conventional anti-cancer therapies. It was found that CA4DP (250 mg/kg)
      significantly decreased tumour perfusion within 30 minutes after injection and
      maintained this decrease for several hours, although there was a return to normal
      by 24 hours. Similar changes were seen in the tumours bioenergetic and
      oxygenation status. The drug also significantly increased tumour necrosis and had
      a small inhibitory effect on tumour growth. It was also able to enhance the
      tumour response to radiation and hyperthermia, when given at the same time or 30
      minutes after the radiation and hyperthermia, respectively. Giving the drug 1
      hour after cisplatin injection only resulted in a tumour response that was no
      greater than additive. These results confirm the anti-vascular effects of CA4DP
      and demonstrate its potential to enhance the anti-tumour activity of conventional
      therapy.

PMID- 10949678
TI  - [Safety in anesthesia-from a "culture of blame" to a culture of safety].

PMID- 10949679
TI  - [Anesthesiologic management in the treatment of patients with cystic fibrosis].
AB  - OBJECTIVE: Improvements in the management of patients with cystic fibrosis (CF)
      result in increased life expectancy. Thus it is likely that anesthetists will see
      this patients with increasing frequency. This study describes our experiences in
      the anesthetic management of CF patients. METHODS: We descriptively and
      retrospectively reviewed the records of all CF patients from 1981 until 1997 who
      underwent elective surgery in our department of ear, nose and throat and in whom
      general anesthesia was required. RESULTS: 199 anesthetics in 53 patients were
      reviewed. Premedication with midazolam (0.4 +/- 0.07 mg/kg) were given orally in
      163 of the 199 anesthetics (82%). In 45 anesthetics the induction was performed
      by Inhalation with halothane (23%). Atropine (0.21 +/- 0.11 mg/kg) was used in 69
      cases for induction. 57 pulmonary function tests were performed preoperatively
      mostly showing no severe abnormalities. We documented 10 perioperative
      respiratory complications (5%) in 199 procedures. No patient died at hospital.
      CONCLUSION: In patients with cystic fibrosis undergoing minor ear, nose and
      throat surgery who do not show significant reduction in pulmonary function
      anesthesia can be safely carried out.

PMID- 10949681
TI  - [Accuracy of intraoperative urinary bladder temperature monitoring during intra
      abdominal operations].
AB  - OBJECTIVE: This study investigates whether the site of abdominal surgery or the
      urine flow rate affects the accuracy of urinary bladder temperature monitoring.
      METHODS: After approval by the local ethics committee we studied 7 patients
      during upper abdominal and 10 patients during lower abdominal surgery.
      Temperatures were recorded with a Hi-Lo Temp Esophageal-Stethoscope (Mallinckrodt
      Medical) and a Foley Catheter Temperature Sensor FC400-18 (Respiratory Support
      Products, Mallinckrodt Medical). Each probe and its recording unit were
      calibrated over a range of 30-40 degrees C against a reference quartz thermometer
      (Hewlett Packard Model 2801 A) in a water bath before the investigation. Urine
      flow rate was measured using a urometer. Temperatures and urine flow rate were
      recorded every 30 min. Agreement between the methods of measurement was assessed
      as described by Bland and Altman. RESULTS: 124 measuring points could be
      analyzed. Bladder temperature had a bias (B) of -0.06 degree C compared to
      oesophageal temperature. Limits of agreement (LOA; +/- 2 s) were +/- 0.68 degree
      C. In upper abdominal surgery (B: 0.02 degree C; LOA: +/- 0.42 degree C) a higher
      precision of oesophageal temperature estimation could be demonstrated compared to
      lower abdominal surgery (B: -0.14 degree C; LOA: +/- 0.82 degree C). Lower urine
      flow rates generally increased the limits of agreement. Regarding lower abdominal
      surgery the bias additionally increased to -0.22 degree C. CONCLUSION: Urinary
      bladder temperature recording is a clinically acceptable method to measure core
      temperature during abdominal surgery. The accuracy during lower abdominal surgery
      is decreased compared to upper abdominal surgery, especially in case of a urine
      flow rate below 250 ml/h.

PMID- 10949680
TI  - [Premedication in maxillofacial surgery under total intravenous anesthesia .
      Effects of clonidine compared to midazolam on the perioperative course].
AB  - OBJECTIVE: The effects of the currently favoured preanaesthetic drugs
      (benzodiazepines, alpha 2-adrenoceptor agonists) on the perioperative course are
      inadequately investigated for new ways of performing anaesthesia with recently
      introduced drugs (e.g. remifentanil). Therefore clonidine and midazolam were used
      for premedication in maxillo-facial surgery under total intravenous anesthesia,
      and the perioperative courses were analyzed. METHODS: Thirty patients (ASA 1-2)
      were included in the present doubleblinded, prospective study. 60-90 minutes
      preoperatively these patients got an oral premedication with 5 micrograms kg-1
      clonidine or 100 micrograms kg-1 midazolam. For anaesthesia a standardized
      procedure with propofol, remifentanil and rocuronium was performed. After
      induction of anaesthesia the infusion of remifentanil was regulated by using
      spectral edge frequency (target-SEF90, 10-13 Hz). The efficiency of the
      premedication as well as the emergence and recovery were assessed by using
      established standardized tests. The perioperative stress response was assessed by
      recording the effects on haemodynamic parameters (NIBP. heart rate. Holter-ECG).
      RESULTS: Referring to the effects of premedication (sedation, anxiety) there were
      no differences between the groups. The clonidine group required a lower
      remifentanil rate in keeping a steady-target-SEF90 (-24%). The time until
      emergence and recovery was not significantly different. Even the occurrence of
      PONV, VAS or the postoperative analgetic requirement did not differ between the
      two groups. However, the incidence of postoperative shivering was significantly
      higher in the midazolam group. Intraoperatively the values of MAP were quite
      equal between the groups. However, heart rate was significantly lower in the
      clonidine group. Postoperatively both MAP as well as heart rate were lower in the
      clonidine group. Furthermore, in the midazolam group there was a significantly
      higher cumulative duration of tachycardia (heart rate > 100 min-1; following
      descripted as medium with 25% and 75%-percentage; clonidine: 29/0/563 sec.:
      midazolam: 1058/232/3171 sec.). CONCLUSION: After remifentanil supplemented
      anesthesia there is, especially in the postoperative period, a benefit in using
      clonidine compared to the premedication with midazolam.

PMID- 10949683
TI  - [Anesthesia in vascular surgery. I].

PMID- 10949682
TI  - [Nasotracheal intubation with laryngeal mask and fiber bronchoscope].
AB  - An alternative way to the usual mode of nasotracheal intubation is described. 50
      patients had to be intubated nasotracheally for surgical procedures. After
      induction of anaesthesia and insertion of the laryngeal mask a fiberoptic
      bronchoscope was nasally inserted during sufficient breathing. After view of the
      laryngeal mask, it was taken out and a tube via fiberoptic bronchoscope was
      placed endotracheally. Way and avoidance of complications by this method are
      described.

PMID- 10949685
TI  - [In Process Citation]

PMID- 10949684
TI  - [Inducing spontaneous respiration at the end of surgery].

PMID- 10949686
TI  - [Emergency pain treatment--ambulatory intravenous morphine titration in a patient
      with cancer pain].
AB  - Even when the guidelines for cancer pain management are followed, acute severe
      pain requiring immediate treatment will occur in some patients. Titration with
      intravenous morphine may provide fast and efficient pain relief and give an
      indication of the amount of opioid necessary for continuous treatment. In
      cooperation with a general practitioner we performed an intravenous morphine
      titration in a patient with severe cancer pain at home. Adequate analgesia was
      reached with 20 mg intravenous morphine. Blood pressure, cardiac frequency and
      oxygen saturation did not change. No side effects were reported during the
      titration, and the previous regimen with tramadol 150 mg per day was switched to
      slow release morphine 300 mg per day. This medication was prescribed by the
      general practitioner and provided good pain relief until the patient died two
      weeks later. We conclude that intravenous morphine titration may be performed
      even in cancer patients at home, adequate monitoring, however, should be
      available.

PMID- 10949687
TI  - [Molecular medicine--perspectives for anesthesiology and intensive care
      medicine].
AB  - The past few decades have seen a profound development in biological sciences. The
      great progress in molecular biology has provided an enormous potential of new
      instruments for highly specific and sensitive insights into the etiology and
      therapy of human disease. Among these first the prototype technique "polymerase
      chain reaction" (PCR) results in improved diagnostic procedures. The
      contributions of recombinant DNA technology in defining the molecular pathology
      of common disorders and of diagnostic molecular techniques for risk
      stratification are used as examples to reveal the clinical relevance of this
      innovative tool and its modifications. In addition, the potential use of modified
      nucleic acid fragments as a therapeutic drug (gene therapy) is mentioned.

PMID- 10949688
TI  - Semicontinuous production of lipase by Acinetobacter radioresistens in presence
      of nonwoven fabric.
AB  - The effect of a hydrophobic nonwoven fabric on the lipase production by
      Acinetobacter radioresistens was investigated with semicontinuous culture. The
      fermentation medium contained n-hexadecane as the carbon source. The nonwoven
      fabric was made from nylon 6 and coated with an acrylic resin. Equipping the
      nonwoven fabric around the baffles of a 2.5-L agitated fermentor could provide a
      fine dispersion of n-hexadecane, thus enhancing lipase production. The
      improvement on lipase yield by using the nonwoven fabric was found to be
      comparable to that of using an emulsifier (gum arabic). Compared with the
      corresponding culture in the absence of nonwoven fabric, the employment of the
      nonwoven fabric could significantly enhance both lipase yield and volumetric
      productivity.

PMID- 10949689
TI  - Production and secretion patterns of cloned glucoamylase in plasmid-harboring and
      chromosome-integrated recombinant yeasts employing an SUC2 promoter.
AB  - To understand the differences in production and secretion patterns between
      plasmid-harboring and chromosome-integrated recombinant yeasts, the two
      recombinant Saccharomyces cerevisiae yeasts, containing the structural
      glucoamylase STA gene and the SUC2 promoter, were investigated. Both systems were
      regulated by glucose concentration in the culture broth. First, the glucoamylase
      activity per gene copy number of the chromosome-integrated recombinant yeast was
      2.8- to 5.6-fold higher than that of the plasmid-harboring recombinant yeast.
      Overburdened owing to high copy number, the plasmid-harboring recombinant yeast
      gave lower glucoamylase activity per gene copy number. Second, the efficiency of
      signal sequence was compared; the secretion efficiency of glucoamylase in the
      plasmid-harboring recombinant yeast was higher than that in the chromosome
      integrated recombinant yeast at 96 h of cultivation (74 vs 65%). We postulated
      that the higher level of secretion efficiency of the plasmid-harboring
      recombinant yeast resulted because the production level did not reach the
      capacity of the secretory apparatus of the host yeast. However, the specific
      secretion rate was much higher in the chromosome-integrated recombinant yeast
      even though the final secretion efficiency was lower. The lower secretion rate in
      the plasmid-harboring recombinant yeast could be explained by an adverse effect
      caused by higher production rate. Finally, the optimal glucose concentration for
      glucoamylase production in the chromosome-integrated recombinant yeast culture
      was lower than that in the plasmid-harboring recombinant yeast culture owing to
      gene dosage effect.

PMID- 10949690
TI  - Immobilization of alkaliphilic Bacillus sp. cells for xylanase production using
      batch and continuous culture.
AB  - Agar-immobilized alkaliphilic Bacillus sp. AR-009 cells were used for xylanase
      production using batch and continuous culture. In a batch culture, maximum enzyme
      production was observed after 48 h and remained high up to 72 h. In repeated
      batch cultivation, immobilized cells produced an appreciable level of xylanase
      activity in seven consecutive batches without any significant decline in
      productivity. For continuous xylanase production, immobilized cells were packed
      in a jacketed glass column and sterile medium was continuously pumped. A stable
      continuous production of xylanase was observed over a period of 1 mo. The
      volumetric productivity of the continuous culture was 17-fold higher than the
      batch culture using free cells.

PMID- 10949691
TI  - Effect of Escherichia coli chaperonin GroELS on heterologously expressed human
      immunodeficiency virus type 1 reverse transcriptase in vivo and in vitro.
AB  - The two subunits of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (HIV-1 RT), p66 and p51, were coexpressed in Escherichia coli along
      with the E. coli chaperonin system GroEL/GroES. Coexpression increases the yield
      of heterodimeric HIV-1 RT by a factor of 4 to 5 and improves the nucleic acid
      binding affinity of HIV-1 RT by a factor of 1.6. We have analyzed the reasons for
      the improvements. The total increase in yield of HIV-1 RT can be attributed to an
      accumulation of RT subunits in the cells (factor of about 2.8) and an increased
      growth of the E. coli cells (factor of about 1.4). One reason for the
      accumulation in the cells is an improved stability of HIV-1 RT subunits toward
      bacterial proteases. In vitro studies showed that the nucleic acid binding
      affinity of HIV-1 RT purified from cells that did not coexpress GroELS was
      stimulated by adding purified GroELS (approx 1.5-fold), whereas HIV-1 RT stemming
      from cells coexpressing GroELS was stimulated only marginally (approx 1.1-fold).
      The in vivo as well as the in vitro studies suggest that the chaperonin interacts
      with HIV-1 RT and therefore affects the folding process of HIV-1 RT.

PMID- 10949692
TI  - Production of citric acid using immobilized conidia of Aspergillus niger.
AB  - Conidia of Aspergillus niger were immobilized in calcium alginate gel for the
      production of citric acid. First, the type of the preactivation medium, together
      with the preactivation period, was investigated. It was found that A. niger
      requires a 2-d preactivation period at a 0.05 g/L NH4NO3 concentration. Second,
      preactivated cells were used to determine the effects of nitrogen concentration
      and the flow rate of oxygen and air on the production of citric acid. Maximum
      citric acid production was attained with medium containing 0.01 g/L of NH4NO3.
      The rate of citric acid production in the nitrogenous medium was 33% higher when
      oxygen was used instead of air during the production phase. This corresponds to
      an increase of 85% when compared to production when neither oxygen nor air was
      fed into the system. In the nonnitrogenous medium citric acid concentration
      remained similar regardless of the use of air or oxygen. However, in the
      nonnitrogenous production medium, citric acid production was not influenced
      considerably when oxygen was used instead of air. The advantage of using
      immobilized cells is that production is achieved easily in the continuous system.
      Therefore, citric acid production was also tested using a packed-bed bioreactor,
      and an increase in productivity by a factor of 22 was achieved compared to the
      batch system.

PMID- 10949693
TI  - Purification and characterization of an extracellular alpha-L-arabinofuranosidase
      from Fusarium oxysporum.
AB  - An alpha-L-arabinofuranosidase from Fusarium oxysporum F3 was purified to
      homogeneity by a two-step ion exchange intercalated by a gel filtration
      chromatography. The enzyme had a molecular mass of 66 kDa and was optimally
      active at pH 6.0 and 60 degrees C. It hydrolyzed aryl alpha-L-arabinofuranosides
      and cleaved arabinosyl side chains from arabinoxylan and arabinan. There was a
      marked synergistic effect between the alpha-L-arabinofuranosidase and an endo-(1-
      >4)-beta-D-xylanase produced by F. oxysporum in the extensive hydrolysis of
      arabinoxylan.

PMID- 10949694
TI  - Immobilized Streptomyces clavuligerus NP1 cells for biotransformation of
      penicillin G into deacetoxycephalosporin G.
AB  - An investigation was conducted to determine whether immobilized resting cells of
      Streptomyces clavuligerus NP1, entrapped on a polymeric matrix, are able to
      perform oxidative ring expansion of benzylpenicillin into deacetoxycephalosporin
      G by virtue of their deacetoxycephalosporin C synthase ("expandase") activity.
      Cells entrapped in polyethyleneimine-barium alginate (1.5%) were able to sustain
      activity for at least four 2-h cycles, whereas free resting cells were inactive
      after the second cycle. Although entrapped cells exhibited lower oxidative ring
      expansion activity than free resting cells, immobilization may offer storage
      stability, recyclability, and operational stability for biotransformation of
      penicillins to cephalosporins, thus contributing to the development of a
      biological means for the production of the important industrial intermediate 7
      aminodeacetoxycephalosporanic acid.

PMID- 10949696
TI  - [This is good...continue...improve].

PMID- 10949695
TI  - Kinetic studies and analytical application of cholesterol oxidase and peroxidase
      immobilized to synthetic polymer.
AB  - A method for individual and simultaneous covalent immobilization of cholesterol
      oxidase and peroxidase to copolymer of acrylonitrile with acrylamide is
      described. The effect of immobilization on the catalytic properties of the
      covalently bound enzymes was studied. The immobilized enzymes showed no change in
      pH optima and an increase in temperature optima, activation energy, and Km'
      compared to data received from experiments with soluble enzymes. A small glass
      column packed with immobilized multienzyme complex was used to develop a method
      for manual determination of cholesterol in foodstuffs (e.g., in mayonnaise
      "Olinease"). The method was characterized by high analytical precision
      (coefficient of variation = 2.67%). The results show high correlation with those
      obtained by the Kageyama method (r = 0.986). The method is economical (the enzyme
      carrier conjugate may be used more than 300 times), precise, easy to perform, and
      less time-consuming than the manual methods utilizing soluble enzymes. The
      established manual method can be proposed for cholesterol determination in
      foodstuffs.

PMID- 10949697
TI  - [From large clinical trials to daily practice].

PMID- 10949698
TI  - [Beta blockers: the end of controversy].

PMID- 10949699
TI  - [Anti-aldosterone: the evidence of the RALES study].

PMID- 10949700
TI  - [Angiotensin II antagonists: a promising pathway].

PMID- 10949702
TI  - [How will drugs be prescribed in the future for patients with cardiac
      insufficiency?].

PMID- 10949701
TI  - [Treatment of cardiac insufficiency and the kidney: conflict of interest?].

PMID- 10949703
TI  - [Angioplasty of the left common coronary artery].

PMID- 10949704
TI  - [Angioplasty of post-irradiation arterial disease].

PMID- 10949705
TI  - [Exertion doppler echocardiography and hypertrophic cardiomyopathy].

PMID- 10949706
TI  - [Functional evaluation in interventional cardiology].

PMID- 10949707
TI  - [Videotransmission of surgery: coronary bypass in a beating heart].

PMID- 10949708
TI  - [New technics of cartography for radiofrequency ablation].

PMID- 10949709
TI  - [A revealing right cardiac insufficiency].

PMID- 10949710
TI  - [Coronary spasm, severe ventricular arrhythmias and implantable defibrillators].

PMID- 10949711
TI  - [The tale of the right atrium].

PMID- 10949712
TI  - [Sudden death: from epidemiology to therapeutic management-prevention].

PMID- 10949713
TI  - [Debate: the grand question of sudden death].

PMID- 10949714
TI  - Antinuclear antibodies: the medium is the message.

PMID- 10949715
TI  - The relationship of antiphospholipid antibodies to infections--do they bind to
      infecting agents or may they even be induced by them?

PMID- 10949716
TI  - Is high titre ANA specific for connective tissue disease?
AB  - OBJECTIVE: A positive antinuclear antibody (ANA), while sensitive, is not
      specific for systemic lupus erythematosus or connective tissue diseases (CTD).
      The purpose of the present study was to review those sera with a high titre (> or
      = dilutions above screening) ANA and determine from a review of the charts if
      these higher titres offered a satisfactory specificity for CTD. METHODS: All FANA
      testing in this region is carried out in one of two related laboratories. We
      reviewed the medical records of patients who had a positive ANA at a titre 4
      dilutions above screening at this city-wide laboratory over a 6-month period to
      determine whether this titre ("high titre") may offer relative diagnostic
      certainty. Antibodies to extractable nuclear antigens (ENA) and native DNA were
      also obtained. RESULTS: 422 ANA results were positive at high titre. The medical
      record was available for review in 320 patients, of whom 238 (75%) were seen by a
      specialist physician, almost always including a rheumatologist. Our review
      determined that 35% had a diagnosis of connective tissue disease, 21% had a
      diagnosis of a possible/probable inflammatory disease, 16% had an alternative
      specific diagnosis provided, and in 29% no final disease specific diagnosis was
      recorded but CTD was not suggested to us or the specialist by the data available.
      One or more anti-ENA antibodies and/or anti-DNA were positive in 69 (22%) and 8%
      of the sera tested respectively. CONCLUSION: While long term follow-up is still
      required, a significant proportion of patients with high titre ANA have no CTD at
      the time of testing. Setting a higher cutoff for reporting of ANA may not
      increase specificity sufficiently to make it a useful alternative or addition to
      reporting a positive or negative value at screening titre alone.

PMID- 10949717
TI  - Colour Doppler ultrasonography to detect pannus in knee joint synovitis.
AB  - OBJECTIVE: To determine if colour Doppler ultrasonography can characterise the
      nature of intraarticular echogenic structures and synovial villi more precisely
      than conventional ultrasonography. METHODS: This is a prospective study on 20
      patients--10 with rheumatoid arthritis and 10 with osteoarthritis. Colour Doppler
      ultrasonography of the knee joints was performed prior to total prosthetic
      replacement. Two independent, trained physician ultrasonographers examined the
      knee to be replaced with different ultrasound equipment using colour Doppler and
      power Doppler ultrasonography. The existence and extent of pannus were then
      assessed surgically and histologically. RESULTS: All 9 patients with
      histologically detected pannus had perfused, echogenic, intraarticular structures
      (ultrasonographer 2; ultrasonographer 1: 8 out of 9 patients). Sparse perfusion
      was detected in 1 patient (investigator 1) and in 5 patients (investigator 2)
      with extensive non-destructive synovial proliferation. Colour Doppler and power
      Doppler ultrasonography were equivalent in detecting small intraarticular
      vessels. CONCLUSION: Colour Doppler ultrasonography improves the differentiation
      of intraarticular structures compared to conventional ultrasonography.

PMID- 10949718
TI  - Clinical effects of actarit in rheumatoid arthritis: improvement of early disease
      activity mediated by reduction of serum concentrations of nitric oxide.
AB  - OBJECTIVE: We previously reported the presence of high serum concentrations of
      nitric oxide (NO) in patients with rheumatoid arthritis (RA). In this study we
      evaluated the effect of actarit on patients with early and advanced stages of RA
      and the relationship between RA activity and serum NO levels. METHODS: Thirty
      seven RA patients who were undergoing care at Sasebo Chuo Hospital were entered
      into the study. Patients were divided into two groups based on the severity of
      their disease: group I (stages I and II) and group II (stages III and IV). NO
      concentrations in serum samples were measured by the chemiluminescence method.
      RESULTS: Morning stiffness, the number of tender and swollen joints, grip
      strength, pain score, modified Health Assessment Questionnaire score (mHAQ), ESR,
      CRP and the Lansbury index significantly improved during 24 weeks of treatment in
      group I. Patients in group II did not show improvement in morning stiffness, pain
      score, ESR or CRP during treatment. The concentrations of NO in group I were
      significantly reduced at 8 weeks after administration of actarit. Those in group
      II showed a delayed response; a significant decrease in NO occurred at 20 weeks.
      The improvement in the number of tender and swollen joints, grip strength, pain
      score, mHAQ and Lansbury index noted in group I preceded the fall in NO
      concentrations. CONCLUSION: Our results demonstrate that actarit improves disease
      activity in early phase RA by suppressing serum NO levels. The results suggest
      that NO is a useful marker for monitoring improvement in the early stages of RA.

PMID- 10949719
TI  - Treatment of the idiopathic inflammatory myopathies: a retrospective analysis of
      63 Caucasian patients longitudinally followed at a single center.
AB  - OBJECTIVE: To analyze the therapies used over the past 20 years at a single
      center to treat patients with idiopathic inflammatory myopathies (IIM), and to
      compare their effectiveness. METHODS: Sixty-three Caucasian IIM patients were
      selected for this study based on the following parameters: (i) a definite
      diagnosis of IIM; (ii) a follow-up period of at least one year; and (iii) a
      complete record of clinical and serological data for the course of the follow-up.
      The following data were collected from the patients' records: the first choice
      and subsequent therapies, the patient's response to these treatments, the outcome
      at the end of the follow-up. RESULTS: Two therapeutic approaches were identified:
      steroids alone and the combination of steroids with immunosuppressive drugs. Of
      the 63 patients studied, 36 received steroids alone and 27 received steroids plus
      immunosuppressors. Sixteen patients did not respond to the initial therapy, 33
      showed a stable response, and 14 experienced a relapse in disease activity during
      the follow-up. No statistically significant differences among these 3 groups of
      patients were observed with respect to sex, age at disease onset, diagnosis, CPK
      levels at disease onset, and therapeutic approach. CONCLUSION: Corticosteroids
      represent the mainstay of IIM therapy, both as the first choice treatment and as
      maintenance therapy. The use of immunosuppressive agents should be restricted to
      those patients with severe contraindications to steroid treatment.

PMID- 10949720
TI  - Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated
      vasculitides.
AB  - OBJECTIVE: To assess circulating immunoregulatory cytokines and soluble surface
      markers of T and B cell activation in the plasma of patients with Wegener's
      granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis
      (MPA) during active and inactive disease, in order to establish their value in
      discriminating between disease entities and as markers of disease activity.
      METHODS: Plasma levels of IL-4, IL-5, IL-10, IL-12, IL-13, IFN-gamma and soluble
      CD23, CD26 and CD30 were determined by enzyme-linked immunosorbent assay in
      patients with WG (n = 21), CSS (n = 19) and MPA (n = 14) during active disease
      and remission. RESULTS: Concerning cytokines, no differences were observed for
      IFN-gamma, IL-4, IL-5 and IL-13. Plasma levels of IL-12 were decreased in all
      subgroups of patients. On the contrary, IL-10 levels were significantly elevated
      only in patients with CSS. Levels of sCD30 were significantly increased in
      patients with active generalized WG and CSS, but not in those with MPA and
      localized WG, correlating with the disease extent and activity. sCD26 levels were
      markedly decreased in patients with generalized WG, CSS and MPA and increased
      towards remission. sCD23 levels were slightly, but not significantly increased in
      CSS and generalized WG. CONCLUSION: Regarding the investigated immunoregulatory
      cytokines (Th1/Th2 type), only the measurement of plasma levels of IL-10
      discriminated CSS from WG and MPA. The reported data could indicate a similar
      status of T cell activation in generalized WG and CSS, and possibly a shift in
      peripheral immunity towards a more humoral dominated immune response. The
      differences observed between patients with the localized and generalized forms of
      WG seem to reflect the clinically known biphasic course of this disease.

PMID- 10949721
TI  - Probing antinuclear antibody specificities by peptide phage display libraries.
AB  - OBJECTIVE: To uncover the specificities of autoantibodies to nuclear proteins
      (ANA) in patients with juvenile rheumatoid arthritis (JRA). METHODS: Peptide
      ligands for ANA were selected by panning random peptide phage display libraries
      on antibodies binding to HEp-2 cells. Positive phage clones were identified by
      the immunoscreening technique. RESULTS: Groups of peptides were identified, some
      of which share the core motifs of KTTTnPY, RVADnL/I or RnNSPL. Perinuclear and
      nuclear staining of HEp-2 cells were obtained with patient serum antibodies
      binding to the phage displaying the core peptide motifs. In contrast, no
      significant reactivity was seen with the antibodies binding to the wild type
      phage. Antibodies to the phage displaying peptides containing some of the core
      motifs were detected more frequently in ANA-positive as compared to ANA-negative
      JRA patients. Homology search with the selected core motifs revealed a
      significant homology with a number of human nuclear proteins and proteins from
      potential infectious agents that could serve as trigger in the breakdown of
      tolerance. CONCLUSION: Panning of phage display libraries on antibodies reacting
      with cellular structures can lead to the identification of their specificities.
      Thus, the peptide epitopes reported here constitute additional information that
      may lead to the development of diagnostic tests and the identification of the
      parental antigens that initiated the B cell responses in patients with JRA.

PMID- 10949722
TI  - Radiographic progression of knee osteoarthritis in a Czech cohort.
AB  - OBJECTIVE: To determine the 5-year radiographic progression of osteoarthritis
      (OA) of the knee in a Czech cohort. METHODS: 139 patients with idiopathic OA were
      followed for 5 years, receiving only physical therapy and non-steroidal
      antiinflammatory drugs as needed. Weight-bearing radiographs of both knees were
      performed at the initial and final evaluation by a single technician using the
      same instrument and a standardized procedure. Radiographs were evaluated using
      the Kellgren-Lawrence scale (KL). Joint space width (JSW) was determined by 2
      independent trained readers, and discrepancies re-reviewed. RESULTS: JSW
      decreased 0.39 +/- 0.95 mm in 5 years, or 0.078 +/- 0.19 annually. The reduction
      of JSW was greatest in the KL grade III radiographs (0.099 +/- 0.18 mm). The
      smallest reduction in JSW was seen in those with KL grade I (0.044 +/- 0.14 mm).
      However, only 25% of those with KL stage II or stage III demonstrated any change
      in JSW over the 5-year period. The reduction in JSW was not constant, being most
      rapid in the first year and then much slower. The coefficient of variation (CV)
      of the method was good (intra- and inter-observer CV 3.6%). CONCLUSION: This 5
      year follow up of Czech patients with OA of the knee demonstrated a low rate of
      radiographic progression of JSW. The most rapid progression appeared in KL stage
      III. The progression was most rapid in the first year.

PMID- 10949723
TI  - Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS)
      recognizes only an epitope expressed by cardiolipin/beta 2-glycoprotein-I (beta
      2GPI) complex and induces APS.
AB  - OBJECTIVE: As the antiphospholipid syndrome (APS) is characterized by antibodies
      which bind negatively charged phospholipids either directly or mainly through
      different target epitopes located on the beta-2-glycoprotein-I (beta 2GPI)
      molecule, the aim of this study is to describe an additional target epitope for
      anti-cardiolipin binding. METHODS: The binding characteristics of affinity
      purified anti-cardiolipin antibodies from a patient with monoclonal gammopathy
      associated with clinically overt APS were studied; inhibition studies were also
      carried out. These antibodies were used for the active induction of experimental
      APS. RESULTS: The affinity purified anti-cardiolipin antibodies were found to
      bind a target epitope created by the complex of cardiolipin/beta 2GPI, while not
      reacting with a complex composed by another phospholipid (phosphatidylserine/beta
      2GPI), as confirmed by direct binding and competition assays. Immunization of
      naive mice with this unique affinity purified anti-cardiolipin antibody resulted
      in the induction of experimental APS (thrombocytopenia, prolonged coagulation
      timed and fetal resorptions). The anti-cardiolipin/beta 2GPI injected mice
      developed high titers of mouse anti-cardiolipin/beta 2GPI antibodies with the
      same binding characteristics as the human antibody which was used for disease
      induction. CONCLUSION: APS is a unique syndrome that is characterized by a
      diversity of pathogenic anti-phospholipid antibodies which may explain the
      diversity of clinical manifestations reported in patients.

PMID- 10949724
TI  - HLA class III region and susceptibility to rheumatoid arthritis.
AB  - OBJECTIVE: We examined the contribution of the HLA class III region in
      susceptibility to rheumatoid arthritis (RA). METHODS: Patients with RA, healthy
      subjects and homozygous typing cell (HTC) lines were typed for HLA class I (A, B,
      C), class II (DR, DQ) and class III (D6S273, Bat 2, and TNFa microsatellites, and
      HSP70 promoter region) alleles by molecular techniques. RESULTS: Based on the
      distribution of microsatellites D6S273, Bat2 and TNFa, and HSP70 promoter region
      alleles in HTCs and homozygous unrelated individuals, a class III region
      haplotype, D6S273 138-HSP70c-Bat2 138-TNFa2 was identified. This haplotype showed
      a significant primary association with susceptibility to RA in DRB 1 QKRAA/QRRAA
      epitope-negative patients. CONCLUSION: Since the QKRAA/QRRAA epitope does not
      provide any risk for disease susceptibility in RA-susceptibility DRB1 epitope
      negative patients, the present data suggest that the class III region haplotype
      D6S273 138-HSP70c-Bat2 138-TNFa2 provides an additional risk for the development
      of RA. These results show that two regions in MHC, class II (DRB1) and class III
      (D6S273 138-HSP70c-Bat 2 138-TNFa2), contribute to susceptibility to RA and more
      completely define the risk for development of the disease.

PMID- 10949725
TI  - Antiphospholipid antibodies in leprotic patients: a correlation with disease
      manifestations.
AB  - OBJECTIVES: Previous studies showed that antiphospholipid antibodies (aPL) are
      frequent in the sera of leprosy patients and are most probably directed against
      body tissue cardiolipins. Some groups have demonstrated differences between the
      binding specificity of "autoimmune-aPL" and "non-autoimmune-aPL". It is widely
      accepted that a plasma protein, beta 2-Glycoprotein I (beta 2-GPI), is required
      for the binding of autoimmune anticardiolipin antibodies (aCL) to cardiolipin.
      However, some reports suggested heterogeneity of leprosy aCL with respect to
      their beta 2-Glycoprotein I (beta 2GPI) dependency, although no thromboembolic
      complications have been reported. This study was designed to assess the
      specificity of aPL by investigating the prevalence of aCL, anti
      phosphatidylserine (aPS), anti-phosphatidylinositol (aPI), anti-beta 2GPI and
      antiprothrombin (aPT) antibodies, and evaluate their clinical significance in a
      group of patients with lepromatous leprosy. PATIENTS AND METHODS: 35 lepromatous
      leprosy patients were selected randomly from an Egyptian leprosarium as a study
      group. 35 normal household contact controls were selected matching the study
      group for both sex and age. aCL, aPS, aPI, aPT, anti-beta 2GPI and beta 2
      dependent aCL antibodies were investigated by ELISA in all patients and controls.
      RESULTS: aCL antibodies were more frequent in leprosy patients than in controls
      [13/35 (37%) vs. 3/35 (9%), respectively, p = 0.02] and significantly correlated
      with Raynaud's phenomenon, skin nodules, chronic skin ulcers and urticarial skin
      rash. No association was found with hypopigmentation, hyperpigmentation and
      saddle nose. None of the patients presented aPS nor aPI. Only 1 subject from the
      control group presented aPI along with aCL. aPT were present in 2/35 (5.7%) and
      anti-beta 2GPI in 1/35 (2.9%) leprotic patients. None of the individuals from the
      control group presented aPT nor anti-beta 2GPI. CONCLUSIONS: An association was
      found between the presence of aCL and certain dermatological manifestations of
      leprosy, such as Raynaud's phenomenon, skin nodules, chronic skin ulcers and
      urticarial skin rash. As in other infectious diseases, there was a lack of beta
      2GPI-dependency and an absence of thrombotic complications.

PMID- 10949727
TI  - Long-term low molecular weight heparin therapy for severe Raynaud's phenomenon: a
      pilot study.
AB  - OBJECTIVE: To investigate tolerability and efficacy of low molecular weight (LMW)
      heparin therapy in patients with severe Raynaud's phenomenon. METHODS: A
      prospective parallel group study comparing patients receiving regular
      subcutaneous LMW heparin (n = 16) with a matched control group (n = 14).
      Endpoints were change in Raynaud's attack severity, non-invasive vascular studies
      or serum levels of circulating soluble adhesion molecules. RESULTS: There was
      overall improvement in Raynaud's attack severity during heparin therapy (p =
      0.0002). This was observed after 4 weeks, and was maximal by 20 weeks. Mean
      finger blood flow recovery time improved, and serum levels of circulating ICAM-1,
      VCAM-1 and E-selectin were lower at completion of heparin therapy, but changes
      did not reach statistical significance. CONCLUSION: This study suggests that LMW
      heparin therapy is well tolerated, and potentially beneficial, in patients with
      severe Raynaud's phenomenon, and justifies further evaluation.

PMID- 10949728
TI  - Relationship between pulmonary function and exercise tolerance in patients with
      ankylosing spondylitis.
AB  - OBJECTIVE: It is a well-known fact that pulmonary function is altered in
      ankylosing spondylitis (AS) mainly due to the restriction of chest wall
      movements. The objective of this study was to investigate whether alterations in
      pulmonary function affected exercise capacity. METHODS: Twenty male patients with
      definite AS and 20 age-matched healthy male controls were recruited for the
      study. All subjects were assessed for functional status by BASFI and physical
      activity level. Measurement of chest expansion and lumbar spinal flexion by the
      modified Schober method were performed. Pulmonary function tests and exercise
      testing on a treadmill using the Bruce protocol were performed. RESULTS: The
      physical activity level was similar in both groups. In the AS group the mean
      BASFI score suggested good functional capacity, while chest expansion and
      modified Schober measurements were significantly lower and pulmonary function
      tests revealed restrictive lung disease. The results of the exercise tolerance
      test were similar in both groups except for the rate of perceived exertion.
      CONCLUSION: This study demonstrated that exercise capacity in AS patients is not
      influenced by the limitation of chest wall movements, probably due to the
      maintenance of moderate physical activity along with an active life style.

PMID- 10949726
TI  - Polymorphonuclear leukocyte myeloperoxidase levels in patients with Behcet's
      disease.
AB  - Myeloperoxidase was measured in the plasma and in the supernatants of
      polymorphonuclear granulocyte cultures from patients with Behcet's disease. High
      levels were found in both plasma and supernatants from patients with active
      disease. The addition of pentoxifylline to granulocyte cultures determined a
      significant decrease of myeloperoxidase levels in active patients only.
      Hyperactive neutrophils are present during the course of Behcet's disease and may
      be considered of importance in the pathogenesis of the vascular lesions.

PMID- 10949729
TI  - Pseudogout: timing of attacks and the cosmogeophysical environment.
AB  - OBJECTIVE: To search for a time parallelism between lunar and solar rotation
      cycles and calendar dates of attacks of pseudogout--chondrocalcinosis articularis
      (pyrophosphate arthropathy). METHODS: Seventy-four documented attacks with known
      calendar dates of onset recorded in 16 patients of one family cluster between
      1955 and 1995 were examined in this study. Their daily frequencies during the
      given time span (chronogram) were transformed into frequencies pertaining to
      separate days of the corresponding cycle (plexogram). The latter data were
      processed by the cosinor analysis to test the presence of a priori supposed
      periodicities. RESULTS: The most pronounced time parallelism was found with the
      Bartels solar rotation cycle, covering a period of 27 days. The cosinor
      regression explained 95% of the total variance in the data. The plexogram of the
      attacks displayed 4 clear peaks and 4 troughs. Besides the 27-day cycling, its
      2nd, 3rd, 4th and 5th harmonics, i.e. approximately 14-, 9-, 7- and 5 day rhythms
      were also statistically significant. Some periodic changes were also found during
      lunar cycles. The maximum frequency was encountered shortly after the full moon
      and after the moon perigee. CONCLUSION: A causal connection between fluctuations
      of the geomagnetic field, such as that during solar rotation and perhaps also
      lunar cycles, and the occurrence of pseudogout attacks could exist and should be
      studied more extensively.

PMID- 10949730
TI  - Effects of IV cyclophosphamide on HIV viral replication in a patient with
      systemic lupus erythematosus.
AB  - Several cases of patients with concomitant SLE and HIV infection have been
      reported in the literature; however, the effect of immunosuppressive therapy on
      HIV replication has not been described. We present the case of a 46 y/o woman
      with a ten-year history of HIV infection who was treated with IV cyclophosphamide
      for SLE nephritis. She had a positive HIV Western Blot just a few months before
      the diagnosis of SLE. Serum levels of HIV RNA had been persistently non
      detectable since the assay became available. The patient was not receiving any
      antiretroviral therapy, raising doubts about the diagnosis of HIV infection.
      After 3 pulses of IV cyclophosphamide, HIV RNA levels went up to 135,720
      copies/ml. Shortly after discontinuation of therapy viral levels were again
      undetectable. This case shows one of the possible clinical scenarios in patients
      with coexistent HIV infection and SLE. In our patient SLE appears to provide some
      immunologic defense against viral replication. Cross-reactivity of autoantibodies
      with HIV proteins may play a role in this mechanism. Effective immunosuppressive
      therapy suppresses this protection and leaves the immune system vulnerable to HIV
      reproduction. Treatment in these cases can be difficult and should be
      individualized in an attempt to achieve a balance between control of viral
      infection and SLE activity.

PMID- 10949731
TI  - "Bamboo spine" starts to bend--something is wrong.
AB  - A typical complication of ankylosing spondylitis with an atypical patient history
      is reported and the topic is discussed. The diagnosis of a spinal fracture may be
      difficult in a "bamboo spine".

PMID- 10949732
TI  - Intravenous treatment with immunoglobulins may improve chronic undifferentiated
      mono- and oligoarthritis.
AB  - We previously reported on 8 young patients with undifferentiated mono- and
      oligoarthritis whose synovial tissue tested positive for Parvovirus B19 DNA by
      PCR. Three of these patients remained clinically undifferentiated and suffered
      from progressive inflammatory disease despite conventional therapy and repeated
      synovectomy. Intravenous treatment with immunoglobulin (0.4 g/kg body weight over
      5 days) resulted in marked improvement in 2 of the 3 patients, allowing them to
      avoid repeated synovectomy during follow-up periods of 7 and 10 months,
      respectively.

PMID- 10949733
TI  - Hypergammaglobulinemic purpura of Waldenstrom: report of 3 cases with a short
      review.
AB  - Benign hypergammaglobulinemic purpura of Waldenstrom (HGPW) is an uncommon cause
      of non-thrombocytopaenic purpura that may create diagnostic difficulties. The
      presence of constitutional symptoms associated with prominent immunological
      abnormalities may raise alarm, leading to extensive and often unnecessary
      investigations. This report describes 3 young women with HGPW. Clinical features
      were characterised by recurrent episodes of bilateral asymmetrical palpable
      purpuric lesions on the lower extremities that were precipitated by a prolonged
      increase in hydrostatic pressure (e.g. prolonged standing, tight stockings etc.)
      associated with constitutional features. In one patient the condition was
      secondary to Sjogren's syndrome with type IV renal tubular acidosis. Laboratory
      abnormalities included a persistently elevated erythrocyte sedimentation rate,
      marked polyclonal hypergammaglobulinemia, and high titers of rheumatoid factor
      and anti-nuclear antibody of the anti-SSA (anti-Ro)/anti-SSB(anti-La) subsets.
      This topic is reviewed briefly with the emphasis that in its 'primary' form this
      condition could be considered a 'benign' systemic immunoinflammatory disease that
      requires neither extensive investigations nor any aggressive form of therapy.
      Greater awareness of HGPW may increase the frequency of its diagnosis, especially
      in the patient group with non-thrombocytopenic purpura or the so-called cutaneous
      vasculitic syndromes with 'palpable purpura'.

PMID- 10949735
TI  - Mevalonate kinase deficiency and Dutch type periodic fever.
AB  - Dutch type periodic fever (DPF) is an autosomal recessive hereditary fever
      syndrome. Cases have been reported worldwide, the majority from France and The
      Netherlands. From infancy the patients suffer fever attacks that recur every 2-8
      weeks, often precipitated by immunizations, infections or emotional stress. Fever
      lasts 2-7 days and can be accompanied by malaise, headache, diarrhea, abdominal
      pain, vomiting, skin rashes, arthralgia, arthritis, tender lymphadenopathy,
      hepatosplenomegaly, and oral and genital ulcers. Laboratory evaluation during
      fever shows granulocytosis and elevated acute phase reactants. DPF is caused by a
      deficiency of the enzyme mevalonate kinase (MK). Besides DPF, the spectrum of MK
      deficiency includes a severe phenotype, mevalonic aciduria (MA). MA patients have
      less residual MK activity, leading to substantially higher urinary mevalonic acid
      excretion than in DPF. Mevalonic aciduria is characterized by mental retardation
      and dysmorphic features in addition to the clinical features of DPF. At the
      genomic level, several mutations of varying severity have been identified. The
      DPF phenotype is caused by one particular mild missense mutation. Most patients
      are compound heterozygotes for this mutation and a more severe mutation. The
      mechanism by which MK deficiency leads to fever is not understood. The vast
      majority of DPF patients have persistently elevated serum IgD and can be
      classified as having hyperimmunoglobulinemia D and periodic fever syndrome
      (HIDS). Conversely, most HIDS patients have MK deficiency and hence DPF, but the
      two disorders do not overlap entirely.

PMID- 10949734
TI  - Primary aspergillosis of the larynx in a patient with Felty's syndrome.
AB  - Herein we report the first case of primary aspergillosis of the larynx in a
      patient with Felty's syndrome. A 53-year-old man, a florist by profession, with a
      12-year history of rheumatoid arthritis and on treatment with steroids, was
      admitted because of hoarseness, and intermittent fever of 2 weeks' duration. On
      admission, physical examination and laboratory data showed, among other findings,
      splenomegalia and neutropenia. At bone marrow examination, normal cellularity
      with mild dyserythropoiesis was observed. A fiberoptic laryngoscopy showed white
      plaques on both the true vocal cords. Both culture and microscopic examination of
      these lesions provided the diagnosis of invasive process by Aspergillus flavus. A
      computed tomography of the middle ears, paranasal sinuses, and chest was normal.
      Thus, primary aspergillosis of the larynx and Felty's syndrome was diagnosed, and
      the patient was successfully treated with granulocyte colony-stimulating factor
      and systemic antifungal agents. Felty's syndrome, corticosteroid use, and
      occupational risk probably rendered our patient susceptible to Aspergillus
      infection.

PMID- 10949737
TI  - Slow evolution to systemic lupus erythematosus of isolated autoimmune
      thrombocytopenia.

PMID- 10949736
TI  - Etanercept and urticaria in patients with juvenile idiopathic arthritis.
AB  - Etanercept, a tumor necrosis factor receptor p75 Fc fusion protein (TNFR:Fc;
      Enbrel), has preliminarily been shown to be effective in the management of
      methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA).
      Reported side-effects have been minor, for example injection site reactions and
      upper respiratory tract infections, not necessitating discontinuation of the
      medication (1, 2). We report on 2 patients who developed an urticaria-like rash
      with prurigo appearing bilaterally on the extensor surfaces of the elbows
      subsequent to etanercept injections.

PMID- 10949738
TI  - Pseudo-dermatomyositis as a complication of hydroxyurea therapy.

PMID- 10949739
TI  - Antinucleolar antibodies and parvovirus B19 arthritis.

PMID- 10949740
TI  - Erosive psoriatic polyarthritis: a report of 2 asymptomatic cases.

PMID- 10949742
TI  - Calf muscular infarction in a diabetic patient.

PMID- 10949741
TI  - Expression of Fas antigen (CD95) on peripheral blood lymphocytes in Behcet's
      disease.

PMID- 10949743
TI  - Erosive arthritis in juvenile onset Crohn's disease.

PMID- 10949744
TI  - Microscopic perineuritis. An unexpected finding of post-herpetic neuralgia in a
      temporal artery biopsy.

PMID- 10949746
TI  - Labor induction: historic perspectives.

PMID- 10949747
TI  - Anatomy and physiology of the uterine cervix.
AB  - The human uterine cervix undergoes extensive changes during pregnancy. Collagen
      is reorganized and consolidated early in gestation with proliferation and
      hyperplasia of the cellular component. As term approaches, multiple factors work
      together in complex interactions that cause collagen dispersion and the cervix to
      ripen (clinically become softer). Increases in decorin levels, hyaluronic acid,
      and physiologic cell death are in part responsible for this remodeling process.
      As the collagen bundles disperse and lose strength, cytokines, hyaluronic acid,
      collagenases, and elastase possibly work together to allow effacement. Then, the
      mechanical forces of uterine contractions extend the elastin and allow
      dilatation. During dilation, levels of cytokines and hyaluronic acid begin to
      decrease, which may serve to decrease collagenolytic activity and allow the
      cervix to begin the process of repairing itself. Despite this advance knowledge
      of cervical ripening, the signals responsible for the initiation of these changes
      remain to be elucidated. If we can understand the exact mechanisms that affect
      these changes, then we may be better able to address such complex issues as
      cervical incompetence, preterm delivery, postterm delivery, and proper "ripening"
      of the cervix to avoid surgical delivery for arrest disorders of the active
      phase.

PMID- 10949748
TI  - Preinduction cervical assessment.
AB  - Systems of quantifying and scoring cervical factors have been sought for years to
      predict the duration of labor and to determine which patients may successfully
      and safely undergo induction of labor. Early methods of cervical assessment
      generally attempted to classify patients as having favorable or unfavorable
      cervices based on dichotomous variables. Since then, obstetricians have begun to
      appreciate the usefulness of having a single score derived from the degree of
      ripeness of several cervical characteristics. The scoring system that has become
      most prevalent is the Bishop score. This system and its modifications take into
      account the dilation, effacement, consistency, and position of the cervix in
      addition to the station of the presenting part. Many have evaluated and confirmed
      the validity of the Bishop score. Among the factors considered in assigning the
      score, the strongest association with successful labor seems to be with cervical
      dilation. The Bishop score has been criticized for not attributing more
      significance to cervical dilation. However, despite this criticism, none of the
      modifications to the original scoring system have been shown to improve
      predictability. More recently, the use of ultrasound assessment of the cervix has
      been suggested to improve prediction of the success of labor induction. However,
      convincing evidence that this technique provides significant additional
      information when compared to digital examination is lacking. The Bishop score
      would seem to be the best and most cost-effective method currently available to
      assess the cervix and predict the likelihood of success of labor induction and
      the duration of such an induction.

PMID- 10949749
TI  - Nonpharmacologic approaches to cervical priming and labor induction.
AB  - Nonpharmacologic and alternative methods of cervical ripening are highly
      efficacious, safe, and, in general, have more favorable cost advantages when
      compared with their pharmacologic counterparts. Unfortunately, there have been
      limited research efforts to precisely determine the overall usefulness and the
      most clinically efficient application for many of these. These methods also share
      similar time courses to affect cervical change and are, in general, not as rapid
      as pharmacologic applications. Thus, limitations of time may ultimately determine
      the choice between alternative methods and pharmacologic modalities. Most of
      these alternative methods require more than 12 to 18 hours, and some even days to
      accomplish favorable changes in the cervix to promote ripening and subsequent
      labor initiation. These methods have also been shown to be efficient and safe,
      the most important criteria for any ripening agent, for both the maternal and
      fetal compartments. These alternative methods will continue to occupy an
      appropriate place in the armamentarium of cervical ripeners and labor-inducing
      agents.

PMID- 10949750
TI  - Pharmacology of oxytocin and prostaglandins.
AB  - Significant advances have been made in the last 20 years in our knowledge about
      the subcellular events occurring during myometrial contractions and cervical
      ripening and in the mechanism of action of oxytocin and prostaglandins. These
      advances have been instrumental in furthering our understanding of the mechanism
      of action of inhibitors of uterine contractility and have opened the door to
      clinical trials of agents such as specific COX-II inhibitors that may have the
      potential to inhibit labor without serious maternal or fetal side effects. There
      is still a long way to go, however, before all the complex actions of oxytocin
      and prostaglandins can be understood at a subcellular level, particularly the
      mechanism of action of prostaglandins in the process of cervical ripening.

PMID- 10949751
TI  - Prostaglandin E2 preparations for preinduction cervical ripening.
AB  - PGE2 is an effective agent for cervical ripening. It is most effective when
      administered intravaginally. Patients with unfavorable cervices who begin labor
      during cervical ripening have greater gestational ages, more baseline uterine
      activity, more initial uterine activity in response to PGE2, and lesser cesarean
      delivery rate than those patients who do not begin labor during cervical
      ripening. However, PGE2 should not be continued or administered when the patient
      is in active labor because it leads to unacceptable rates of hyperstimulation.
      Unfortunately, cervical ripening with PGE2 has little or no effect on the overall
      cesarean delivery rate.

PMID- 10949752
TI  - Misoprostol for cervical ripening and labor induction: a systematic review of the
      literature.

PMID- 10949753
TI  - Oxytocin for labor induction.
AB  - Induction of labor has increased from 9% to 18% of all U.S. deliveries in recent
      years. Several useful oxytocin induction protocols are available, both from the
      ACOG Practice Bulletin #10 and institutional sources. Higher-dose protocols tend
      to result in fewer cesarean deliveries for dystocia but more "fetal distress."
      There is no consensus as to which protocol is best, and the clinician is advised
      to understand the trade-offs involved and how those trade-offs could relate to
      the clinician's local situation. Given the availability now of prostaglandin
      agents for induction with an unfavorable cervix, the advantage of less
      hyperstimulation in low-dose oxytocin protocols may become increasingly
      important. The most important risks include hyperstimulation (frequent but
      usually brief and well-tolerated), failed induction (occasional and important),
      and uterine rupture in some studies (rare but dangerous). Pain was not a
      sensitive indicator of uterine rupture in a large 1989 study. Fetal heart rate
      changes were much more likely to herald uterine rupture in that study. Oxytocin's
      greatest weakness is that some patients will not respond well to it, especially
      with marked cervical unfavorability. However, given an individual patient whose
      uterus will respond adequately to this drug, oxytocin has the advantage of short
      half-life and the option for prompt cessation if desired. Intrauterine pressure
      catheters with oxytocin usage are usually well-worth their minor risks. Current
      ACOG literature lists induction of labor in the setting of one or more previous
      low-transverse cesarean deliveries as necessitating "special attention" and
      "close patient monitoring." The well-informed clinician will be familiar with the
      issues involved.

PMID- 10949754
TI  - Midtrimester cervical ripening and labor induction.

PMID- 10949755
TI  - Cervical ripening and labor induction after previous cesarean delivery.

PMID- 10949756
TI  - Cervical ripening and labor induction: clinical guidelines.

PMID- 10949757
TI  - Ethical considerations in the incorporation of new technologies into gynecologic
      practice.

PMID- 10949758
TI  - Measuring cost-effectiveness of surgical procedures.
AB  - Our review of CEA of surgical procedures suggests that much of the existing cost
      analysis literature does not adhere to basic recommended analytic guidelines.
      However, those authors who specifically planned to perform a CEA analysis met all
      or nearly all of the methodologic principles (Table 1). Investigators who conduct
      CEA are strongly encouraged to use the many outstanding methodologic reviews for
      CEA. An example of threshold analysis was presented by Gray et al in their CEA of
      laparoscopy versus laparotomy for the treatment of ectopic pregnancy. They
      calculated that cost per successful treatment would be equal between the two
      strategies at an initial failure rate of 32% for laparoscopy (compared with their
      baseline value of 19%). This type of analysis is helpful, in addition to
      sensitivity analyses, to identify the value of a variable that results in an
      equal outcome. In the only cost-utility analysis performed on gynecologic
      surgery, Sculpher studied the trade-offs between a less invasive, less costly
      procedure (transcervical resection of the endometrium) with a more invasive, more
      costly, and more effective procedure (abdominal hysterectomy) to treat
      menorrhagia. Hysterectomy resulted in an incremental cost of 1,500 British pounds
      per QALY during 2 years of follow-up. This is much less than the range of $30,000
      to $100,000 that represents a currently acceptable C/E ratio. Grover et al
      evaluated the cost-effectiveness of performing a concurrent hysterectomy in women
      undergoing bilateral salpingo-oophorectomy. They observed that in 45-year-old
      women, the additional concurrent procedure dominated the alternative strategy of
      bilateral salpingo-oophorectomy, being both less expensive and increasing average
      life expectancy. The concurrent hysterectomy strategy also dominated for women
      aged 55, but both with less cost-savings and gains in life expectancy compared
      with 45-year-old women. Selecting an appropriate time frame for the analysis is
      difficult and may dramatically affect the results of the analysis. The time frame
      should be long enough to measure all clinically relevant costs and benefits. For
      example, Kung et al compared the cost per cure of stress urinary incontinence of
      laparoscopic and open Burch procedures. The probability of cure after each
      procedure was estimated from a retrospective cohort of 62 women with a mean
      follow-up of 1.2 years for the laparoscopic Burch strategy and 2.7 years in the
      open Burch strategy. The authors found that the laparoscopic Burch dominated,
      with lower costs and a higher cure rate. However, the analysis would be more
      informative with much longer follow-up, because most women who undergo an
      incontinence procedure have a life expectancy far greater than 1 to 2 years.
      Ramsey et al performed an economic analysis to assess the long-term costs of
      behavioral therapy, pharmacotherapy, and surgical therapy used for stress urinary
      incontinence. They found that in the short-term, behavioral and pharmacotherapy
      were less costly. However, if life expectancy was equal to or greater than 3.5
      years, surgical therapy was least costly. In many articles that evaluate the cost
      of managing ectopic pregnancy, only short-term costs of the procedures and follow
      up visits are considered. Mol et al considered a longer time frame and also
      included the costs of infertility management based on the future probability of
      conception correlated with the different management strategies. Selection of an
      effectiveness measure after surgical intervention is often difficult and
      controversial. For benign disease, life years or QALYs will be minimally affected
      by a reasonably safe intervention. In the short-term, utility may be negatively
      affected by surgery and recovery. In longer-term analyses, these effects will be
      diluted by time and be negligible. Intermediate measures such as days of
      hospitalization averted or lives saved are often more appropriate for gynecologic
      interventions than are longer-term outcomes such as lif

PMID- 10949759
TI  - Endometrial ablation: electrocautery and laser techniques.

PMID- 10949760
TI  - Endometrial cryoablation and thermal ablation.

PMID- 10949761
TI  - Laparoscopic-assisted vaginal hysterectomy: a review of usefulness and outcomes.

PMID- 10949762
TI  - Laparoscopic pelvic reconstructive surgery.

PMID- 10949763
TI  - Laparoscopic surgeries for urinary incontinence.

PMID- 10949764
TI  - Laparoscopic surgery for gynecologic cancers.
AB  - In conclusion, laparoscopic techniques are useful for the evaluation and
      treatment of selected gynecologic malignancies and provide major benefits to
      patients. The benefits, however, can be expected only from gynecologic
      oncologists well-versed in advanced laparoscopic techniques. Results must be
      interpreted cautiously, depending on the laparoscopic expertise of the reporting
      authors. Numerous questions remain unanswered, particularly those associated with
      long-term recurrences and survival. The use of laparoscopic procedures for
      gynecologic malignancies must be considered investigational until adequate long
      term survival data are available.

PMID- 10949765
TI  - Comparison of tubal ligation reversal procedures.

PMID- 10949766
TI  - New surgical mesh.

PMID- 10949767
TI  - Bone anchors in urogynecology.

PMID- 10949768
TI  - Tension-free vaginal tape for the treatment of stress urinary incontinence.

PMID- 10949769
TI  - Spinal cord neuromodulation for voiding dysfunction.
AB  - A clear understanding of the pathophysiology and neurophysiologic effect of
      neuromodulation is lacking. Apparently there is a balance of efferent and
      afferent negative and positive feedback loops that are augmented by external
      electrical stimulation. This effect may be dramatic even in patients who have
      have not benefited from virtually every other form of treatment.

PMID- 10949770
TI  - Critique of new gynecologic surgical procedures: surgery for vulvar vestibulitis.

PMID- 10949771
TI  - A brief history of the randomized controlled trial. From oranges and lemons to
      the gold standard.
AB  - This article discusses the history and development of randomized clinical trial
      methodology, the reasons for its status and authority as a method of therapeutic
      evaluation, and the continuing role of clinical judgement in designing,
      interpreting, and applying the findings of trials.

PMID- 10949772
TI  - Evidence-based medicine. Interpreting studies and setting policy.
AB  - The ascendancy of EBM has been accompanied by a greater awareness of its
      shortcomings. It is increasingly evident from the cost, length, and difficulty of
      performing RCTs that studies cannot be launched to address every question in
      medicine. Good evidence is often lacking in medicine. Epistomologists question
      the very notions of evidence and the suitability of current study designs and
      measurement tools to research the salient issues of concern to patients and
      others concerned with quality. Lack of evidence of effectiveness does not prove
      ineffectiveness, yet, in reaction to EBM, insurance companies and government
      often make this inference to justify decisions to withhold coverage or research
      support. The unbridled enthusiasm for the evidence-based practice guideline of
      the early 1990s has been tempered by a more mature understanding of its
      limitations. Not many practice guidelines are developed well, and the
      implementation of flawed guidelines can cause harm. The seven-step process
      outlined earlier is slow, laborious, and expensive (sometimes costing hundreds of
      thousands of dollars). Moreover, there is little evidence that either the rigor
      of the methods or the guidelines themselves have a meaningful effect on practice
      behavior or patient outcomes. To the most cynical observers, the only consistent
      beneficiaries of guidelines are payers, who use guidelines with considerable
      success in reducing costs, lengths of stay, and utilization rates. Even ardent
      advocates of guidelines acknowledge the evidence that disseminating reviews and
      recommendations, by itself, fails to motivate clinicians to increase delivery of
      effective interventions and to abandon ineffective ones. This absence of response
      has stimulated a closer look at the barriers to behavior change and the design of
      thoughtful implementation strategies that begin with, but reach beyond, simple
      guidelines. Tools such as reminder systems, standing orders, academic detailing,
      peer review and audit, feedback, and health system changes recognize that knowing
      what to do is only one piece of an increasingly complex puzzle. The competitive
      marketplace of managed health care has added new economic influences on clinician
      behavior but is also fueling private-sector interest in good research. Patients,
      clinicians, and policy makers will continue to seek better data concerning what
      works in medicine and what does not.

PMID- 10949773
TI  - Hypothesis testing in clinical trials.
AB  - In designing and analyzing any clinical trial, two issues related to patient
      heterogeneity must be considered: (1) the effect of chance and (2) the effect of
      bias. These issues are addressed by enrolling adequate numbers of patients in the
      study and using randomization for treatment assignment. An "intention-to-treat"
      analysis of outcome data includes all individuals randomized and counted in the
      group to which they are randomized. There is an increased risk of spurious
      results with a greater number of subgroup analyses, particularly when these
      analyses are data derived. Factorial designs are sometimes appropriate and can
      lead to efficiencies by addressing more than one comparison of interventions in a
      single trial.

PMID- 10949774
TI  - Epidemiologic evidence and causal inference.
AB  - Preventing cancer depends on the ability to recognize and remove causal factors.
      In current practice, the methods used to judge cause from epidemiologic, clinical
      trials and biologic evidence include systematic narrative reviews, criteria-based
      inference methods, and meta-analysis. Subjectivity and values play a key role in
      the practice of causal inference, especially in selecting criteria and assigning
      rules of evidence to those criteria. Judging cause is a central concern of
      physicians, epidemiologists, and other public health professionals committed to
      cancer prevention.

PMID- 10949775
TI  - Primary cancer prevention trials.
AB  - Great progress has been made in cancer chemoprevention during the past 2 decades.
      Nevertheless, the field could benefit from the experiences of investigators
      studying the prevention of cardiovascular disease. During the past 50 years,
      prevention of cardiovascular disease has gone from a dream to a reality, with
      major clinical impact. The trend during the last 30 years has been impressive and
      sustained. From 1987 to 1994, there was a sustained major decrease in age
      adjusted mortality from coronary heart disease in both men (from 3.1 to 2.2 per
      thousand persons) and women (from 1.1 to 0.9 per thousand persons). This trend is
      believed to have resulted from improvements in the treatment of myocardial
      infarction and, more substantively, from improvements in secondary prevention.
      This explanation is consistent with earlier computer simulations of trends in
      cardiovascular mortality during the 1980s, which estimated that 25% of the
      declines were attributable to primary prevention and 70% were caused by
      reductions in risk factors or treatment. The greatest effect of primary
      prevention had previously been noted in the late 1960s and 1970s. Most of these
      important findings occurred before cholesterol-lowering drugs became widely
      available, so further improvements are expected. Researchers in cancer prevention
      should follow in the footsteps of their cardiovascular colleagues. The tools are
      now available to make prevention of cancer a clinical reality. As the science of
      prevention improves, it must be remembered that effective and efficient
      preventive services do not help if they are not used. It is difficult to motivate
      practitioners and patients to implement preventive services. Also, preventive
      services are often considered a luxury. Persons without health insurance and
      those covered by Medicaid are much more likely to be diagnosed with late-stage
      cancer; therefore, they are key cohorts to target for effective preventive
      approaches. Finally, the most effective cancer prevention program will probably
      use both rational drug therapy targeting specific risk factors and public health
      efforts to promote healthy lifestyle choices in the population at large.

PMID- 10949776
TI  - Cancer screening.
AB  - Especially in the emotionally charged field of cancer screening, which can have
      substantial public health implications for large numbers of healthy, asymptomatic
      people, it is important to achieve strong levels of evidence before promulgating
      new screening tools. This review of screening study methodology is intended to
      help the reader weigh such evidence and to evaluate reports which appear in the
      literature. It is an attempt to go beyond the often-stated intuition that early
      cancer detection finds cancers when they are easier to treat, at a time when
      survival is best. Examples tell us that sometimes this assumption has been true,
      sometimes not. A familiarity with the hidden biases in the supposition can be
      translated into everyday medical practice for screening tests in general. The
      practitioner can then match the strength of recommendation with the strength of
      the evidence behind the recommendation.

PMID- 10949777
TI  - Therapeutic studies.
AB  - This article discusses the problems in basic design, conduct, and interpretation
      associated with phases I, II, and III of the cancer clinical trials and explains
      the various statistical solutions to these problems. The fundamental problem
      common to all three trials is achieving a correct and precise answer to the
      question posed to inform future testing and treatment while protecting trial
      patients from receiving treatment that has demonstrated excessive toxicity or
      lack of clinical efficacy. This shared problem gives rise to statistical designs
      with basic similarities across the three trial types.

PMID- 10949778
TI  - The importance of quality-of-life endpoints in clinical trials to the practicing
      oncologist.
AB  - Quality-of-life research has helped describe and draw attention to the human side
      of cancer treatment. The field has made tremendous advances and has influenced
      the treatment of cancer. The practicing oncologist can benefit greatly by keeping
      abreast of developments in this field and applying them to the selection of
      treatment modalities based on both treatment efficacy and the patient's wishes.
      In the future, quality-of-life research will probably continue to be integrated
      into the practice of oncology.

PMID- 10949779
TI  - Intermediate markers as surrogate endpoints in cancer research.
AB  - Because studies with surrogate cancer endpoints can be smaller, faster, and
      substantially less expensive than those with frank cancer outcomes, the use of
      surrogate endpoints is undeniably attractive. This attractiveness is likely to
      grow in coming years as the rapidly advancing discoveries in cell and molecular
      biology generate new therapies requiring testing and new markers that could
      plausibly serve as surrogates for cancer. Surrogate endpoint studies can
      certainly be suggestive. They continue to play a legitimate role in phase II
      studies, and they may give the right answers about intervention effects on or
      exposure associations with cancer. The problem is the uncertainty attached to
      most potential surrogates. Except for those few surrogates that are both
      necessary for and developmentally relatively close to cancer, the existence of
      plausible alternative pathways makes inferences about cancer from many surrogates
      problematic. Merely being on the causal pathway to cancer does not in itself
      constitute surrogate validity. It is the totality of causal connections that is
      critical. There is, unfortunately, a fairly extensive history of quite plausible
      surrogate markers giving the wrong answer about various chronic disease
      therapies. There is no reason to believe that cancer surrogacy is immune to such
      inferential difficulties. This article is, in part, an invitation, even a plea,
      for researchers to carry out the investigations necessary to evaluate potential
      surrogates, particularly surrogate-cancer studies and intervention or exposure
      surrogate-cancer mediation analyses. Such studies are needed to generalize from
      surrogate endpoint findings to cancer. There is, however, an implicit and perhaps
      unavoidable irony here: the large, long, expensive studies required to evaluate
      potential surrogates fully are precisely the studies that surrogates were
      designed to replace. The exposure dependence alluded to earlier complicates
      matters further: establishing validity for a given surrogate for one intervention
      or exposure vis-a-vis cancer does not necessarily translate into validity for
      another intervention or exposure. One can enhance the inferential strength of
      surrogacy by using further "downstream" markers. Results of trials with CIN3 as
      an endpoint are arguably more persuasive than those from intervention studies
      with HPV infection endpoints. Similarly, one could consider only the advanced
      adenoma (> or = 1 cm, villous elements, or high-grade dysplasia) as the primary
      endpoint in adenoma recurrence trials. The inferential gain, however, comes with
      substantial costs: studies with CIN3 endpoints must be much larger than those
      with HPV infection endpoints; adenoma recurrence trials with sufficient rates of
      recurrence of advanced adenomas must be five or six times larger than trials with
      any recurrent adenomas as endpoints. A law emerges here: in using surrogate
      endpoints, inferential certainty is directly associated with study cost. In other
      words, one gets what one pays for. The problems inherent in using surrogate
      endpoints need not be regarded as a cause for pessimism in cancer research. If
      anything, the limitations of surrogacy are reminders of the complexity of cancer
      causation and affirm the continued importance of large clinical trials and
      observational epidemiologic studies with explicit cancer endpoints.

PMID- 10949780
TI  - Prognostic factors for hematologic cancers.
AB  - This article reviews the molecular biology of hematologic cancers and the current
      understanding of prognostic factors for these cancers. Specific molecular
      biomarkers that have potential as prognostic factors for various hematologic
      cancers are discussed. Quantitative and statistical methods of evaluating the
      usefulness of prognostic factors are presented.

PMID- 10949781
TI  - Simulation modeling of outcomes and cost effectiveness.
AB  - Modeling will continue to be used to address important issues in clinical
      practice and health policy issues that have not been adequately studied with high
      quality clinical trials. The apparent ad hoc nature of models belies the
      methodologic rigor that is applied to create the best models in cancer prevention
      and care. Models have progressed from simple decision trees to extremely complex
      microsimulation analyses, yet all are built using a logical process based on
      objective evaluation of the path between intervention and outcome. The best
      modelers take great care to justify both the structure and content of the model
      and then test their assumptions using a comprehensive process of sensitivity
      analysis and model validation. Like clinical trials, models sometimes produce
      results that are later found to be invalid as other data become available. When
      weighing the value of models in health care decision making, it is reasonable to
      consider the alternatives. In the absence of data, clinical policy decisions are
      often based on the recommendations of expert opinion panels or on poorly defined
      notions of the standard of care or medical necessity. Because such decision
      making rarely entails the rigorous process of data collection, synthesis, and
      testing that is the core of well-conducted modeling, it is usually not possible
      for external audiences to examine the assumptions and data that were used to
      derive the decisions. One of the modeler's most challenging tasks is to make the
      structure and content of the model transparent to the intended audience. The
      purpose of this article is to clarify the process of modeling, so that readers of
      models are more knowledgeable about their uses, strengths, and limitations.

PMID- 10949782
TI  - Genetic testing.
AB  - New research developments in the molecular genetics of cancer have led to the
      feasibility of cancer genetic testing. At present, genetic test results can
      better inform individuals at risk about appropriately tailored strategies for
      cancer screening and prevention. In the future, more persons will be eligible for
      genetic evaluation; in particular, if it is shown that patients with cancer who
      are carriers of germline mutations respond differently to treatments, genetic
      testing may be warranted. Consideration needs to be given to the appropriate
      delivery of genetic risk assessment and testing. There is a great potential for
      misinterpretation of gene test results and for adverse psychosocial consequences
      for patients. Genetic counseling is an important component in cancer risk
      assessment and management, particularly in helping persons at risk understand the
      implications of gene test results in the context of their experience with cancer
      and surveillance.

PMID- 10949783
TI  - Quality control of oncology clinical trials.
AB  - This article discusses issues that are essential to ensuring the reliability of
      the conclusions of oncology clinical trials. Though quality control is important
      at every stage of a well-run clinical trial, the authors focus on the quality of
      the data as evidenced by the results and conclusions of the study. Good quality
      control principles and practices are discussed for study planning, design,
      conduct, analysis, and interpretation.

PMID- 10949784
TI  - Meta-analysis in hematology and oncology.
AB  - In 1992, a review article about meta-analysis identified only 15 meta-analyses of
      randomized, controlled trials of cancer therapy. Since then, the total number of
      meta-analyses in this field has increased almost sixfold. More importantly, the
      number of randomized, controlled trials in this discipline has also grown
      tremendously. The expansion in the literature will provide a fertile ground for
      future meta-analyses. The quality of the recent publications has also improved.
      An ongoing world-wide effort, the Cochrane Collaboration, is systematically
      assembling and synthesizing several hundred thousand randomized, controlled
      trials to improve the delivery of health care. Meta-analysis has many important
      advantages. It allows the viewing of the complete picture of the evidence. The
      advent of meta-analysis has sensitized researchers to issues of quality and has
      improved methodology in clinical research. Detection and explanation of bias and
      heterogeneity are prime objectives of meta-analysis in clinical research. An
      array of methods has been developed that allows a better understanding of bias
      and heterogeneity, beyond simple averaging of results from diverse studies. Meta
      analyses of individual patient data, in particular, may promote the development
      of international collaborations. Several examples of their application are
      already available in oncology. Meta-analysis may point out deficiencies in the
      study design of past and current studies, suggest the need for new studies, and
      inform researchers about the size and design of these studies. In the end, meta
      analysis helps to integrate evidence and make recommendations for medical care
      and medical practice.

PMID- 10949785
TI  - [Neuroradiology].

PMID- 10949786
TI  - [Thoracic imaging. Major trends: increasing resolution, reducing radiation].

PMID- 10949788
TI  - [Urogenital diseases].

PMID- 10949787
TI  - [Digestive system radiology].

PMID- 10949789
TI  - [Senology].

PMID- 10949790
TI  - [Progress in cardiovascular imaging in 1999].

PMID- 10949791
TI  - [Pediatric radiography].

PMID- 10949792
TI  - [Http://www. Medical imaging.com].

PMID- 10949793
TI  - [Image networks].

PMID- 10949794
TI  - [Scanning].

PMID- 10949795
TI  - [Digital radiology].

PMID- 10949796
TI  - [Ultrasonography].

PMID- 10949797
TI  - [MRI].

PMID- 10949798
TI  - [Nuclear medicine].

PMID- 10949799
TI  - Endoscopic plantar fasciotomy: a retrospective analysis of results in 53
      patients.
AB  - This retrospective study analyzes satisfaction of patients who had undergone an
      isolated endoscopic plantar fasciotomy (EPF) between January 1994 and January
      1997. A subjective survey was completed and returned by 53 patients (a total of
      69 feet), and a chart review was performed to determine final outcome.
      Postoperative follow-up averaged 7.2 months (range, 4-42 months). Postoperative
      pain levels were scored on a 7-point scale at 1 week, 1 month, and 6 months.
      Forty-three patients (81.1%) were satisfied with the EPF procedure and 10
      patients (18.9%) were unsatisfied.

PMID- 10949800
TI  - Five-year follow-up results of instep plantar fasciotomy for chronic heel pain.
AB  - The results of a 5-year follow-up of patients who underwent surgical partial
      release of plantar fascia with plantar skin incision for treatment of chronic
      heel pain are presented. Evaluation included survey results from both a modified
      Mayo Scoring System and a list of specific questions developed by the authors.
      Thirty-three feet of 30 patients are evaluated. Thirty of the 33 feet studied
      achieved good or excellent results, scoring 80 or better on a 100-point scale.
      Ninety percent pain relief was achieved in 27 of the 33 feet studied (81.8%). A
      satisfaction rate of 90% or better was found with 30 of the 33 feet studied
      (90.9%). Long-lasting complications were described by five patients, including
      opposite foot pain, dorsal foot pain after extended activity, scar tissue
      discomfort, callus at scar area, and continued heel pain.

PMID- 10949801
TI  - The modified Hohmann bunionectomy: a retrospective review.
AB  - A retrospective review of 35 modified Hohmann bunionectomies is presented with
      analysis of objective radiographic and subjective patient questionnaire results.
      Thirty-five modified Hohmann bunionectomies were performed, on 29 patients over a
      6-year period with follow-up ranging from 11 months to 5 years and 11 months. The
      modification involves resection of a triangular wedge from the first metatarsal,
      to minimize shortening, and utilizes two points of fixation. In total, 88% of
      those patients responding to our questionnaire had either excellent or good
      results. The Hohmann bunionectomy is a valuable procedure in alleviating symptoms
      caused by hallux abductovalgus.

PMID- 10949802
TI  - Mechanical comparison of two extensor tendon repairs of ankle tendons.
AB  - Complete disruption of the extensor tendons is commonly encountered with
      lacerations to the dorsal aspect of the ankle. The purpose of this study was to
      compare two tendon repairs (modified Krackow and Kessler-Tajima) to determine
      which repair was stronger in an anatomical cadaver model. Twenty tendons (10
      extensor hallucis longus and 10 tibialis anterior tendons) from 10 fresh-frozen
      cadaver legs were lacerated and then repaired with either a modified Krackow or
      Kessler-Tajima repair. Each tendon repair was tested for gap formation and
      maximum load failure. Results showed that the mean force to produce gap formation
      in the modified Krackow repair was 64.7 N in the extensor hallucis longus and
      82.3 N with the tibialis anterior. Mean gap formation for the Kessler-Tajima in
      the extensor group was 26.0 N and the tibialis anterior was 41.8 N. This
      represented a 40% and 50% greater resistance to gap formation for the modified
      Krackow in these groups. With maximum load failure, the mean for the modified
      Krackow was 99.5 N for the extensor hallucis longus and 126.8 N for the tibialis
      anterior, while the Kessler-Tajima was 45.6 N and 72.1 N for these groups. This
      represented a 45% and 58% greater difference in the maximum load failure for the
      modified Krackow. Statistical analysis using a Student's t-test (p < .05) showed
      that there was a significant statistical difference between the two repairs for
      gap formation and maximum load failure. The authors conclude that the modified
      Krackow is stronger than the Kessler-Tajima repair.

PMID- 10949803
TI  - Isolated lateral tarsometatarsal joint arthrodesis: a case report.
AB  - There are few references in the literature to an isolated lateral tarsometatarsal
      joint arthrodesis. Most references include it as a component of a Lisfranc's
      joint arthrodesis, which usually involves arthrodesis of at least the
      intermediate tarsometatarsal joint. A case report involving the treatment of an
      isolated lateral tarsometatarsal joint arthrosis is presented. Dowel grafting of
      the fourth and fifth metatarsocuboid joints was initially attempted but resulted
      in nonunion. Revisional inlay bone grafting afforded solid arthrodesis in this
      case. Although there are some detrimental biomechanical effects of the procedure,
      they do not outweigh the need to alleviate the debilitating symptoms that can be
      associated with degenerative arthritis of the lateral tarsometatarsal joint.

PMID- 10949804
TI  - Necrotizing fasciitis in the lower extremity: a review and case presentation.
AB  - Necrotizing fasciitis is a rare but potentially fatal disease which is often
      confused with cellulitis. By examining the pathogenesis, clinical presentation,
      treatment, and a representative case study, this article proposes to lend a
      broader perspective to this infection. Emphasis is placed on the necessity of
      surgical debridement in combination with antibiotic therapy to minimize the
      possible morbidity associated with this condition.

PMID- 10949805
TI  - Papillary eccrine adenoma of the heel: a case report.
AB  - Papillary eccrine adenoma is a rare, slow-growing cutaneous tumor of sweat gland
      origin. It is a benign lesion that occurs most often in the distal extremities.
      Only 33 cases have been reported in the literature with few located in the distal
      lower extremity. There have been no cases reported in the podiatric literature.
      The clinical and surgical history of a case report of a papillary eccrine adenoma
      in a 35-year-old white male is presented.

PMID- 10949806
TI  - Antibiotic selection for diabetic foot infections: a review.
AB  - Foot infections account for about 20% of all hospitalizations in people with
      diabetes and at least 50% of all nontraumatic lower-limb amputations performed
      annually in the United States. As many as 25% of all diabetics are expected to
      develop severe foot problems at some point in their lifetimes. Diabetic foot
      infections are generally more severe and more difficult to treat than infections
      in nondiabetics. This is due to impaired microvascular circulation, neuropathy,
      anatomical alterations, and impaired immune capacity in diabetic patients. Most
      moderate-to-severe soft-tissue diabetic foot infections are polymicrobial (i.e.,
      due to gram-positive, gram-negative, aerobic, and anaerobic pathogens). Empiric
      antibiotic therapy should include broad-spectrum antibiotics capable of covering
      the most common pathogens found in diabetic infections. Other factors to consider
      in antibiotic selection include the severity of the infection, the presence of
      peripheral vascular disease, and the possibility of drug-resistant organisms in
      the infection. This review summarizes the clinical presentation and antimicrobial
      therapy of diabetic foot infections.

PMID- 10949807
TI  - The modified lapidus arthrodesis: technical maneuvers and pearls.

PMID- 10949808
TI  - [Nolite nos contingere. The small difference as exemplified with contact lenses].

PMID- 10949809
TI  - [Glaucoma: playing of wind instruments increases intraocular pressure].

PMID- 10949810
TI  - [Long-term follow-up of 700 trabeculectomies].
AB  - BACKGROUND: A major focus of our study was to determine the value of
      postoperative intraocular pressure (IOP) in predicting the outcome of
      trabeculectomy (TE). PATIENTS AND METHODS: The medical charts of 547 patients
      undergoing glaucoma filtering surgery at the Department of Ophthalmology of the
      University of Cologne from 1987 to 1996 were reviewed. The eyes with congenital
      glaucoma and those treated with anti-metabolites were excluded. RESULTS: Defining
      the qualified criteria for success of trabeculectomy as an IOP </21 mm Hg
      throughout the entire study period, no evidence of progressive disc damage or
      further visual field loss, no decrease in visual acuity and no additionally
      required surgical intervention due to glaucoma, there was a success rate of
      44.4%. In 50% the tonometric failure took place within the first 34 days
      trabeculectomy. No significant difference in survival by sex (p = 0.53), surgical
      technique, limbal versus fornix-based flap (p = 0.28) and by type of glaucoma (p
      = 0.26) was shown. But the patient group with prior argon laser trabeculoplasty
      had a significant lower success rate in terms of normalization of IOP (p = 0.03).
      There was no significant difference in the outcome of trabeculectomy between the
      first and second eye. CONCLUSION: The identification of patients at risk of
      failure in terms of IOP in the early post-operative period is possible, thus,
      closer follow-up and early medical or surgical intervention may be indicated.
      Should trabeculectomy be the therapy of first choice in the early stage of
      glaucoma and in case of failure in the first eye, this would allow options, such
      as the use of anti-metabolites in the second eye.

PMID- 10949811
TI  - [Postoperative inflammatory response to phacoemulsification and implantation of 2
      types of foldable intraocular lenses in pseudoexfoliation syndrome].
AB  - BACKGROUND: Patients with pseudoexfoliation syndrome (PEX) are known to have a
      greater degree of inflammation after cataract surgery when compared to patients
      with senile cataract in otherwise healthy eyes. We performed a randomised,
      prospective study to compare the influence of the intra-ocular lens (IOL)
      material of two different IOLs on the postoperative inflammation of the anterior
      chamber. PATIENTS AND METHODS: 28 eyes of 27 patients with PEX and cataract and
      29 eyes of 29 control patients were included in this study. The IOLs used were
      the hydrophilic, acrylic lens: Bausch&Lomb-Hydroview and the hydrophobic, acrylic
      Alcon Acrysof MA60 lens. The patients were examined preoperatively as well as on
      day 1, 3, 7 and 1, 3, and 6 months after surgery using the Laser flare-cell meter
      (LFCM) KOWA FC 1000. RESULTS: The preoperative flare and cell values were
      significantly higher in PEX eyes as compared to the control group. The values
      decreased after about 1 month to reach values comparable to those in the control
      group. Over the six months period there was no significant difference between the
      values of both lenses in the PEX group except on the first postoperative day
      where the flare and cell values were higher in the Acrysof-lens group. When
      comparing both groups with the Hydroview-lens there was also no significant
      difference, except on day 7, between the PEX group and the control group up to 6
      months after surgery. When comparing both groups with the Acrysof-lens, there was
      a significant difference between the PEX group and the control group until 1
      month after surgery. CONCLUSION: Although PEX-eyes had higher flare and cell
      values up to one month after surgery, we could not determine a significant
      difference, except on the first postoperative day, between both IOLs. A
      significant difference was evident between the PEX and control group in eyes with
      an Acrysof-lens. Using this clinical model, the LFCM highlights only certain
      aspects of biocompatibility of different lens types.

PMID- 10949812
TI  - [Eye complications in 458 children with rheumatoid arthritis].
AB  - BACKGROUND: Besides arthritis or other systemic manifestations, endogenous
      inflammation (most commonly uveitis) can be a symptom of rheumatoid arthritis in
      children. The uveitis of children shows certain differences compared to that in
      adults. This study will show these differences and their incidences. PATIENTS AND
      METHODS: Retrospective analysis of the histories of 458 children that were
      admitted to the pediatric clinic due to rheumatism related diseases. An analysis
      of the general and pediatric data, laboratory results and therapy were combined
      with the ophthalmologic data. RESULTS: 45 (9.8%) of the 458 patients suffered
      from uveitis at least once during the studied time period between 1992 and 1996.
      Most common complications of the therapy were clouding of the lens up to full
      cataract (in both eyes in eight out of nine patients). Seven patients underwent
      cataract operation. Further complications are synechiae, band shaped keratopathy,
      secondary glaucoma and retinal diseases. CONCLUSION: Since the pediatric uveitis
      usually does not take an acute course and since children rarely can articulate
      themselves precisely, a regular ophthalmologic examination of pediatric
      rheumatology patients is necessary, as well as every uveitis in children should
      warrant pediatric-rheumatologic diagnostics. The impact of uveitis is much more
      severe for children when compared to adults, since it not only endangers the
      vision but the whole development of the child.

PMID- 10949813
TI  - [Penetrating and perforating eye injuries in 343 patients due to auto accidents
      before and after compulsory seat belt legislation resulting in fines (1966
      1998)].
AB  - BACKGROUND: Constructional improvements of passengers safety in cars alone did
      not result in a significant decline of open globe injuries in traffic accidents.
      Only after compulsory seat belt legislation was introduced in Germany and Great
      Britain, a 60%-75% reduction in ocular injuries was observed. We examined, how
      the characteristics of severe eye injuries in car accidents changed during the
      last 28 years. PATIENTS AND METHODS: The case records of 343 patients, who
      suffered from open globe injuries during car accidents between 1966 and 1993 and
      were primarily admitted in the University Eye Hospitals of Freiburg and Wurzburg,
      have been analyzed retrospectively. Injuries were evaluated for their extent,
      time of injury (hour and season), age, sex and outcome of visual acuity after
      surgery. RESULTS: Between 1966 and 1984 wind-screen injuries declined slowly from
      25/year to 16/year. Since the introduction of compulsory seat belt legislation in
      Germany in 1984 we observed a sudden reduction to 4 injuries/year, followed by an
      additional slow decline to 2.5 injuries/year. Male/female ratio changed from
      2.1/1 before to 9/1 after 1984. Due to the seat belt legislation, injuries
      declined during summer season (april through september) by factor 7.6, during
      winter season (october through march) by factor 3.8. Injuries during daylight (6
      a.m. to 6 p.m.) decreased more rapidly (by factor 14) than during nighttime (6
      p.m. to 6 a.m.: factor 4). The decline of eye injuries was most pronounced among
      those with an age of less than 23 years (by factor 10.8) and those who were 31-50
      years old (by factor 6.8), but least among those between 23 and 30 years of age
      (2.2). Since 1984, open globe injuries combined with mid-facial and cranial
      fractures increased resulting in a poorer visual outcome: 29% of eyes became
      blind before 1984 and 40% since then due to the higher survival probability of
      very severe accidents. A majority of injured persons still had not fastened their
      seat belt and about 50% were drunk. CONCLUSION: Compulsory seat belt legislation
      introduced in Germany in 1984 was most effective in preventing eye injuries among
      female passengers, during daytime or among persons younger than 23 years.
      However, 23-30 year old male drivers who had not fastened their seat belt, drove
      in darkness or during winter and had drunk alcohol, were still at highest risk
      for an open globe injury. The increase of victims with a combination of open
      globe injuries and midfacial injuries, polytrauma or cerebral trauma may be
      related to the airbag and other improved safety measures.

PMID- 10949814
TI  - [Minimally invasive therapy for clinically complete central retinal artery
      occlusion--results and meta-analysis of literature].
AB  - BACKGROUND: Goal of our study was the comparison of the efficacy of various
      minimal invasive therapeutic regimens for clinically complete central retinal
      artery occlusion (CRAO) and the comparison with the literature. PATIENTS AND
      METHODS: In a retrospective study 93 patients treated for CRAO during the period
      1994-1998 were identified. 65 of these patients with clinically complete
      occlusion without a cilioretinal artery were included in the study. Analysis
      focused on the results of different therapies and the duration of visual
      impairment till starting treatment. RESULTS: The following therapies were used:
      acetazolamide (65%), aspirin (60%), bulbus massage (45%), hemodilution (34%),
      oral pentoxifylline (28%), topical beta blockers (9%), paracentesis (8%), heparin
      (6%). In 15% of all cases an improvement of at least 3 visual acuity gradations
      was achieved. No significant positive influence of any treatment method could be
      identified. Also, a correlation between duration of visual impairment and final
      visual acuity could not be shown. In the literature very different criteria for
      inclusion of patients to the studies and for visual acuity improvement are found.
      When applying comparable criteria to ours most studies show similar results for
      the therapies listed above as well as for paracentesis and the use of carbogen
      (95% O2 and 5% CO2). CONCLUSION: The minimal invasive treatments given above do
      only improve natural course of CRAO in occasional cases. Thus a therapy (
      combination) should be chosen, which is adapted to the individual risk factors
      and is exposing the patient to a low risk by therapy itself.

PMID- 10949815
TI  - [Polymerase chain reaction (PCR) for microbiological diagnosis in refractory
      infectious keratitis: a clinical study in 16 patients].
AB  - BACKGROUND: The identification of the causative pathogen in infectious keratitis
      is possible in only 60% of the cases. The aim of this study was to show if this
      number increases by the use of PCR. PATIENTS AND METHODS: In a series of 16 eyes
      with infectious keratitis corneal specimens were collected for culture and PCR.
      Serology (HSV, VZV, and Borrelia) was performed in all eyes, with exception of
      the 4 eyes presenting an acute form of keratitis, which obviously was bacterial
      origin. RESULTS: In all 4 cases of acute keratitis the causative pathogen
      (Pseudomonas aeruginosa) was detected by both culture and PCR. Of the remaining
      12 eyes PCR was capable to identify the causative pathogen in 11 eyes. In 3 eyes
      herpes simplex virus was detected, in 3 eyes Moraxella catharalis, in 2 eyes
      Borrelia burgdorferii, in 2 eyes varizella zoster virus, and in 1 eye Bartonella
      henselae. Culture was positive in only 2 eyes, infected by Moraxella catharalis.
      CONCLUSIONS: PCR is a useful supplement in the microbiological diagnostic of
      infectious keratitis, in particular if only a small amount of pathogens are
      available (non-acute form) or if the eye has been treated by antibiotics prior to
      the microbiological diagnostic.

PMID- 10949817
TI  - [Diplopia as first symptom of a bronchogenic carcinoma].
AB  - BACKGROUND:  PATIENTS: In about 30% of patients with orbital metastases, these
      metastases are detected before the primary tumour is known. Less than 5% of
      orbital metastases are located in extraocular muscles. We report on a patient
      with diplopia caused by diminished abduction of the left eye as first symptom of
      a bronchogenic carcinoma. PATIENT: A 86-year-old patient presented with a newly
      developed diplopia. On examination, the left eye showed a diminished abduction,
      ptosis and miosis. Pharmacological testing revealed peripheral Horner's syndrome.
      On cranial magnet resonance tomography, the lateral rectus muscle belly was
      enlarged. A chest X-ray showed a large tumour (6 cm in diameter) of the left
      upper lobe with multiple metastases to the lungs. Further examinations revealed a
      large cell bronchogenic carcinoma with metastases to the lungs, adrenal glands,
      and the lateral rectus muscle. CONCLUSIONS: Diplopia caused by metastases to
      extraocular muscles is rare as first sign of a bronchogenic carcinoma. The
      combination of peripheral Horner's syndrome with diminished abduction of the
      homolateral eye primarily suggests a lesion of the cavernous sinus. The
      bronchogenic carcinoma could not be causative for Horner's syndrome in the
      patient presented here, however an undetected tumor-infiltration of the
      postganglionic region cannot be excluded. This case demonstrates that in all
      patients with newly developed diplopia and Horner's syndrome, even in absence of
      orbital signs, apart from a ophthalmological examination detailed radiographic or
      magnetic resonance tomographic imaging is necessary of both skull base and
      orbita.

PMID- 10949816
TI  - [Mutations in the keratin gene as a cause of Meesman-Wilke corneal dystrophy and
      autosomal dominant skin cornification disorders].
AB  - BACKGROUND: Meesmann's corneal dystrophy (OMIM 122,100) is a rare autosomal
      dominant disorder of the corneal epithelium. It manifests in early childhood and
      affects both eyes. The disease is characterized by variable patterned dot-like
      corneal opacities and intraepithelial vesicles, which can be seen by slit-lamp
      examination and retro-illumination. Further signs include punctate erosions,
      lacrimation, photophobia, and blepharospasm. Vision is usually only slightly
      diminished. By histology, the corneal epithelium is irregularly thickened. It
      shows vacuolated epithelial cells and intraepithelial formation of vesicles. By
      electron microscopy fibrogranular aggregates are seen in the cytoplasm of
      epithelial cells. RESULTS: Linkage analyses in descendants of the family
      described by Meesmann and Wilke and other affected kinships showed that the
      putative genetic defect locates within the keratin type I gene cluster on
      chromosome 17 (17q12-21). Molecular genetic analyses in more than ten affected
      families showed that mutations in the cornea-specific keratin genes K3 and K12
      represent the causative genetic defects of the disease phenotype. CONCLUSION:
      Comparative studies in autosomal dominant skin disorders of cornification suggest
      that the mutations identified in patients with Meesmann's corneal dystrophy exert
      dominant negative effects on keratin filament assembly. Disturbed filament
      formation results in intracellular keratin clumping, identifiable as
      fibrogranular aggregates. As a result the mechanical resilience of the affected
      cells and the epithelial tissue appears markedly reduced. Whether abnormalities
      of functionally related structural proteins, e.g. desmosomal components, could
      result in a phenotype similar to Meesmann and Wilke's corneal dystrophy remains
      to be seen.

PMID- 10949818
TI  - [Ganglioglioma of optic nerve in neurofibromatosis type 1. Case report and review
      of the literature].
AB  - BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. In only
      seven cases they have been found within the optic nerve. Two of these cases were
      associated with neurofibromatosis (NF), but a pathogenic link between
      gangliogliomas of the optic nerve and NF still remains controversial. PATIENT:
      Here we report on a 71-year-old patient with a ganglioglioma of the optic nerves
      and NF type 1. Post mortem examination revealed multiple neurofibromas of the
      vagal and left femoral nerves, multiple schwannomas of the small bowel and Lisch
      noduli of both irides. In addition, a spindle shaped thickening of the right
      optic nerve was observed in its intracranial portion. The left optic nerve was
      normal on gross inspection. RESULT: Histologically, tumoral tissue was found in
      both optic nerves. The tumor was composed of two cell types: highly
      differentiated, partly stellate, partly pilocytic astrocytes and, at the rim of
      the axon bundles of the optic nerve, fully developed synaptophysin- and
      neurofilament-antigen-positive ganglion-cells with short corkscrew-shaped
      processes. No mitosis could be found in the neuronal or in the glial cell
      population. In spite of the tumoral involvement of the optic nerves, there has
      been no evidence of visual disturbance. CONCLUSION: Optic nerve tumors in NF most
      often are of glial origin (astrocytomas, pilocytic astrocytomas). Our case
      illustrates the rare condition of a glioneuronal tumor associated with
      neurofibromatosis type 1.

PMID- 10949819
TI  - [Pathophysiology, diagnosis and therapy of three congenital dacryocystoceles].
AB  - BACKGROUND: Congenital dacryocystocele has been rarely described in German
      literature. Congenital obstruction and distention of the lacrimal sac makes it
      necessary to differentiate for various causes. PATIENTS AND METHODS: Three
      infants had congenital dacryocystocele. The diagnosis was made by sonography and
      was established by probing the lacrimal duct and nasal endoscopy that showed a
      white prominent tumor below the lowest conch. RESULTS: Directly after endonasal
      and canalicular opening of the dacryocystocele clear liquid with white detritus
      drained, and the swelling decreased. No further procedure was needed. CONCLUSION:
      The diagnosis of dacryocystocele can be made by inspection, probing the lacrimal
      duct, ultrasound and nasal endoscopy. If probing of the lacrimal duct could not
      easily open the Hasner's membrane, endonasal opening can be performed. The
      cooperation with an ear-nose-throat specialist could lead to the diagnosis of
      dacryocystocele and sufficient treatment without the need for any further
      radiological examinations.

PMID- 10949820
TI  - [Two patients with xerophthalmia].
AB  - BACKGROUND: Xerophthalmia, the eye manifestation of vitamin A deficiency, is one
      of the main reasons of blindness in developing countries but is rare in
      industrial countries. PATIENTS: We report on 2 cases of night blindness and
      conjunctival and corneal xerosis because of hypovitaminosis A. One patient
      developed vitamin A deficiency due to short bowel syndrome resulting from
      gastroschisis. The other patient suffered from primary hypovitaminosis A because
      of malnutrition due to inadequate dietary intake. Electroretinograms were
      consistent with vitamin A deficiency. Their symptoms quickly improved after
      vitamin A substitution. CONCLUSION: Although rare in developed countries,
      ophthalmologists should consider xerophthalmia as differential diagnosis in night
      blindness and conjunctival and corneal xerosis. Early diagnosis and adequate
      treatment can prevent permanent visual loss.

PMID- 10949821
TI  - [Contrast discrimination and street illumination level for traffic at night].

PMID- 10949822
TI  - Preparation of DNA substrates for in vitro mismatch repair.
AB  - Analyses in vitro of correction of DNA mismatches have been pivotal in
      biochemical dissection of mismatch repair pathways. However, the complex
      procedures needed to prepare DNA substrates for mismatch repair have posed
      substantial barriers to investigators who wish to pursue such analyses. Here we
      describe a simple, efficient way to prepare a variety of mismatched DNA
      substrates. We use in our procedure high-copy-number pUC19-derived plasmids, and
      a newly commercially available endonuclease N.BstNBI that makes site-specific
      single-strand nicks. The ability to prepare large substrate quantities in a
      relatively short time and to construct wider ranges of different mismatches in
      various sequence contexts will facilitate future research.

PMID- 10949823
TI  - Construction of adenovirus for high level expression of small RNAs in mammalian
      cells. Application to a Bcl-2 ribozyme.
AB  - A series of plasmid vectors have been generated to allow the rapid construction
      of adenoviral vectors designed to express small RNA sequences. A truncated human
      U6 gene containing convenient restriction sites has been shown to be expressed at
      high levels following electroporation into a series of human cell lines. This
      gene was ligated into a promoterless adenoviral plasmid, and we have generated
      high titer virus by homologous recombination with adenoviral Addl327 DNA in 293
      cells. Recombinant adenovirus containing a hammerhead ribozyme sequence targeted
      toward the Bcl-2 mRNA has been used to transduce a panel of human tumor cell
      lines. We have demonstrated high level expression of the recombinant U6 gene
      containing the ribozyme and reduction of Bcl-2 protein in transduced cells. These
      plasmids are suitable for the development of adenoviral vectors designed to
      express both ribozymes and antisense RNA in human cells.

PMID- 10949824
TI  - Basic principles of quantitative PCR.
AB  - The polymerase chain reaction (PCR) is an extremely sensitive method owing to the
      repetitive multiplication of template molecules. This property is a drawback for
      quantitative measurements because small differences in the multiplication factor
      lead to large differences in the amount of product. Two methods can be used to
      solve the problem of quantification: kinetic methods based on the determination
      or comparison of the amplification factor; and coamplification methods, which
      compare the amount of product to that of a simultaneously amplified standard
      template. An overview of the theoretical background of both methods is presented.
      For selection of a suitable method, both theoretical and practical considerations
      are important. Kinetic methods are the most convenient if PCR can be performed
      without opening the tubes, as in some apparatus using fluorescence detection.
      Coamplification methods can be done without expensive equipment but requires the
      parallel running of several PCR tubes. When the number of initial template
      molecules is close to one, as in the limiting dilution technique, statistical
      considerations become important.

PMID- 10949825
TI  - Quantitative analysis of human DNA sequences by PCR and solid-phase
      minisequencing.
AB  - Reliable quantification by PCR requires careful experimental design and
      conditions, often involving sampling of the PCR reactions at different time
      points or amplifying multiple dilutions of a standard DNA. We describe here an
      accurate, quantitative and easily automatizable solid-phase method based on
      competitive PCR. The PCR products are analyzed by solid-phase mini-sequencing
      after capture of biotinylated PCR products in streptavidin-coated microtiter
      wells and single-nucleotide extension of a specific detection primer by a
      radioactively labelled nucleotide. The results are expressed as numeric cpm
      values, and the incorporated label expresses the relative amount of sequence
      variants in the original template mixture. We have applied the method to
      determination of allele frequencies in pooled DNA samples, of mitochondrial
      heteroplasmy, of gene copy numbers, and to forensic DNA analysis.

PMID- 10949827
TI  - Rapid analysis of amplified double-stranded DNA by capillary electrophoresis with
      laser-induced fluorescence detection.
AB  - DNA amplification technology has been applied to clinical diagnosis of infectious
      disease, genetic disorder, and cancer. After in vitro amplification of a
      particular DNA region, the methods of analysis for these amplified samples play a
      pivotal role in clinical diagnosis. Conventional gel electrophoresis has been
      routinely used in the lab for checking DNA. The whole procedure is time consuming
      and requires more than 1 ng of DNA for detection. To achieve greater performance
      in DNA diagnosis, we demonstrated capillary electrophoresis with laser induced
      fluorescence detection for analysis of amplified DNA. The analysis of DNA could
      be completed within 3 min and the data is directly entered into the computer.
      Considering the automatic and rapid process, we believe that this method could be
      routinely utilized for the clinical diagnosis of amplified DNA products.

PMID- 10949826
TI  - Retroviral-mediated gene transfer in primary murine and human T-lymphocytes.
AB  - Recombinant retroviruses are efficient vectors for introducing genes into many
      mammalian cell types. They are useful in the context of clinical as well as
      experimental applications, owing to the ability to generate high-titer and helper
      free viral stocks. Retroviral vectors are especially appropriate for the
      transduction of primary lymphocytes, because gene transfer is stable and mediated
      by nonimmunogenic vectors. Stable integration in chromosomes of cells undergoing
      clonal expansion ensures that the foreign genetic material will be faithfully
      transmitted to the cells' progeny. However, oncoretroviral vectors derived from
      murine leukemia viruses (MLV) require target cell division to integrate. Here we
      review factors that determine retroviral-mediated gene transfer efficiency in
      primary T-lymphocytes, in particular, T-cell activation status, viral receptor
      expression, and culture conditions.

PMID- 10949828
TI  - Evaluation of natural killer cell activity.
AB  - Natural killer (NK) cells are being appreciated not only for their ability to
      recognize and lyse tumor cells and virus-infected cells but also for their
      immunoregulatory properties. NK cells provide a first line of defense against
      invading pathogens with a two pronged attack, lysis of infected cells and
      secretion of cytokines and chemokines with potent antipathogen effects. This
      article describes the standard chromium release assay, which measures the ability
      of NK cells derived from the peripheral blood to lyse appropriate target cells.

PMID- 10949829
TI  - An efficient method of generating transgenic mice by pronuclear microinjection.
AB  - Genetic transformation of mice using pronuclear microinjection was demonstrated
      by a number of groups in rapid succession in the early 1980's. Since that time,
      studies using transgenic animals have produced major advances in biomedical
      sciences and molecular genetics. More important, it is possible to study the
      molecular basis for tissue and stage-specific expression of genes. We recently
      used this method to generate transgenic mice. DNA fragment (transgene) was
      injected into the pronucleus of one-cell embryos. We describe this simplified
      protocol, which is reliable. With the use of buffered medium M2 for the whole
      process, it is not mandatory to have a CO2 incubator.

PMID- 10949830
TI  - Avidin- or streptavidin-biotin as a highly sensitive method to stain total
      protein on membranes.
AB  - A sensitive method for staining proteins after transfer from polyacrylamide gels
      to nitrocellulose paper is described. Transferred proteins are first derivatized
      by reaction of the nitrocellulose replica with sulfosuccinimidobiotin and are
      then reacted sequentially with streptavidin, rabbit anti-streptavidin, and
      horseradish peroxidase-conjugated goat anti-rabbit IgG antibody. Incubation with
      the enzyme substrate alpha-chloronaphthol, produces dark protein bands against a
      white background. The binding of streptavidin to the proteins is dependent on
      biotin derivatization as demonstrated by competition with biotinylated bovine
      serum albumin or 10 nM biotin. The procedure detects less than 5 ng of
      transferred protein in a single band and is thus 5-10 times more sensitive than
      horseradish peroxidase-conjugated avidin alone. For bovine serum albumin, the
      method is comparable in sensitivity to silver staining of protein in
      polyacrylamide gels.

PMID- 10949832
TI  - Direct digital radiography for caries detection and analysis.
AB  - Recent developments in the field of electronic imaging have provided a new set of
      imaging tools for intra-oral imaging and clinical diagnosis. In this chapter, we
      review the general structure and characteristics of image sensors used in digital
      radiography and their application for clinical caries detection and analysis. An
      overview of the literature, comparing the diagnostic accuracy of digital and film
      based radiography and the impact of image-processing methods, is provided. We
      also describe several approaches for quantitative assessment of radiographic
      images for caries detection and assessment. Examples include digital subtraction
      radiography, and 2-D and 3-D density profiling. To increase the accuracy and
      reduce observer variability the use of 3-D imaging and computer-aided diagnosis
      is presented as future direction for clinical caries diagnosis.

PMID- 10949831
TI  - Visualization of DNA and RNA molecules, and protein-DNA complexes for electron
      microscopy.
AB  - This article provides step-by step instructions for the preparation of double-
      and single-stranded DNA and RNA molecules and protein-DNA complexes for electron
      microscopy (EM). Absorption, spreading, staining, dark-field imaging, and metal
      shadowing techniques are described in detail. A number of examples are
      illustrated on analysis of DNA replication, DNA repair and DNA recombination to
      demonstrate the usefulness of the technique for EM visualisation. Application of
      immunogold labeling of specific protein in DNA-protein complexes is also covered.

PMID- 10949833
TI  - Relationship of surface epithelium concentrations of IL-1 alpha and IL-1 beta to
      clinical inflammation during experimental gingivitis.
AB  - Experimental evidence has clearly demonstrated that IL-1 cytokine levels increase
      in experimental gingivitis (EG) models in response to plaque accumulation
      following the cessation of oral hygiene. These changes in cytokine production are
      reported to occur prior to visible signs of clinical inflammation, and as such
      may represent early markers of gingival inflammation. This clinical study used a
      novel dermal sampling tape as a method to collect cytokines from gingival
      epithelium, as opposed to the more commonly sampled gingival crevicular fluid.
      The primary objective of the study was to examine the relationship between
      changes in cytokine levels and clinical inflammation. Ten subjects participated
      in a 14-day EG model, where 5 days following a dental prophylaxis subjects
      refrained from all oral hygiene measures for 14-days. Clinical measures including
      the Loe-Silness Gingival Index (GI), a bleeding index derived from the GI, and
      the inflammation index (II) were made at baseline prior to the initiation of the
      EG period and following 14 days of EG. Dermal tape samples were collected from
      the right posterior buccal quadrant of each subject at both baseline and day 14.
      The tapes were extracted and the extracts analyzed for both IL-1 alpha and IL-1
      beta by ELISA. Results of this study indicate that over a 14-day EG period
      statistically significant (p < 0.05) increases in GI, gingival bleeding, II, and
      IL-1 alpha were observed (tested by matched-pairs t test and Wilcoxon signed
      ranks test). A directional increase in IL-1 beta was also observed. Linear
      regression analyses demonstrated a strong positive correlation between the number
      of gingival bleeding sites from the region of gingiva sampled with Sebutape and
      IL-1 alpha (r = 0.93), as well as IL-1 beta (r = 0.90). In addition, linear
      regression analyses also demonstrated a strong positive correlation between the
      mean II score from the region of gingiva sampled with Sebutape and IL-1 alpha (r
      = 0.93), as well as IL-1 beta (r = 0.86). Similar correlations were observed for
      whole mouth scores of the number of gingival bleeding sites and mean II with
      respect to IL-1 alpha and IL-1 beta levels. Collectively, these data confirm the
      utility of the dermal tape for sampling epithelium cytokine levels from the
      gingiva and demonstrate a strong positive correlation between IL-1 alpha and IL-1
      beta concentrations and gingival inflammation.

PMID- 10949834
TI  - Imaging of the oral cavity using optical coherence tomography.
AB  - Optical coherence tomography is a new method for noninvasively imaging internal
      tooth and soft tissue microstructure. The intensity of backscattered light is
      measured as a function of depth in the tissue. Low coherence interferometry is
      used to selectively remove the component of backscattered signal that has
      undergone multiple scattering events, resulting in very high resolution images (<
      15 microns). Lateral scanning of the probe beam across the biological tissue is
      then used to generate a 2-D intensity plot, similar to ultrasound images. This
      imaging method provides information that is currently unobtainable by any other
      means, making possible such diverse applications as diagnosis of periodontal
      disease, caries detection, and evaluation of restoration integrity. This chapter
      presents an overview of this exciting new imaging technique and its current
      application to dental diagnosis.

PMID- 10949835
TI  - Advances in measurements of periodontal bone and attachment loss.
AB  - Periodontal probing and measurements using intraoral radiographs are widely
      utilized clinical techniques to measure attachment and bone levels, respectively.
      Determination of progressive disease, healing, or regeneration in clinical
      studies may require maximal sensitivity and attention to measurement error in
      order to assure that changes detected by new methodology are accurate. Both types
      of methods are susceptible to errors due to resolution, repeatability, and
      accuracy of the technique. While both probing and radiographic methods are useful
      in clinical trials they vary widely with respect to these errors. For example,
      manual probing is repeatable to within 1 mm better than 90% of the time, and
      state-of-the-art radiographic methods, such as digital subtraction radiography,
      can detect as little as 1 mg of bony change.

PMID- 10949836
TI  - Analysis of the morphology of oral structures from 3-D co-ordinate data.
AB  - A non-intrusive method is described which can be used to determine the forms of
      oral structures. It is based on the digitising of standard replicas with a co
      ordinate-measuring machine. Supporting software permits a mathematical model of
      the surface to be reconstructed and visualised from captured three-dimensional co
      ordinates. A series of surface data sets can be superposed into a common
      reference frame without the use of extrinsic markers, allowing changes in the
      shapes of oral structures to be quantified accurately over an extended period of
      time. The system has found numerous applications.

PMID- 10949837
TI  - Objective quantification of plaque using digital image analysis.
AB  - Dental plaque is the precursor to many oral diseases (e.g. gingivitis,
      periodontitis, caries) and thus its removal and control are an important aspect
      of oral hygiene. Many of the oral care products available today remove or inhibit
      the growth of dental plaque. Historically, the antiplaque efficacy of products
      was measured in blinded clinical trials where the amount of plaque on teeth is
      assessed via subjective visual grading with predefined scales such as the Turesky
      index. The ability of the examiner to consistently apply the index over time and
      the sensitivity of the scales often leads to large, expensive clinical trials.
      The present invention is an automatic measurement of plaque coverage on the
      facial surfaces of teeth using a digital image analysis technique. Dental plaque
      disclosed with fluorescein is digitally imaged under long-wave ultraviolet light.
      Ultraviolet illumination of fluorescein-disclosed plaque produces an image where
      the pixels of the image can be categorically classified based on color into one
      of five classes: teeth; plaque; gingiva; plaque on gingiva, or lip retractors.
      The amount of plaque on teeth can be determined by summation of the number of
      plaque pixels. The percent coverage is calculated from the number of plaque
      pixels and teeth pixels in the image. The digital image analysis of plaque allows
      facial plaque levels to be precisely measured (RSD = 3.77%). In application, the
      digital image analysis of plaque is capable of measuring highly significant
      plaque growth inhibition of a stannous fluoride dentifrice with as few as 10
      subjects in a cross-over design.

PMID- 10949839
TI  - Recent advances in methods for the assessment of dental calculus--research and
      clinical implications.
AB  - The diagnostic evaluation of supra- and subgingival calculus has remained an
      important research problem for over 40 years. The measurement of calculus remains
      an important objective in both research and office settings. As might be
      expected, the most important advances in diagnostic methods for calculus
      assessment have been derived from cross-fertilization from other technical
      disciplines including engineering, optics and computer science fields. With the
      new methods described herein, clinicians and researchers can look forward to
      important advances in our understanding of the impact of supragingival and
      subgingival calculus on oral health status and periodontal disease progression
      and in the development of treatment modalities for improved calculus control,
      benefiting patients and clinicians alike.

PMID- 10949838
TI  - Application of quantitative light-induced fluorescence for assessing early caries
      lesions.
AB  - Quantitative light induced fluorescence (QLF) is a nondestructive diagnostic
      method for the longitudinal assessment of early caries lesions in time. When a
      tooth becomes carious the fluorescence radiance at the location of the caries
      lesion decreases. The fluorescence image of enamel with incipient lesions can be
      digitized and then the fluorescence loss in the lesion can be quantified in
      comparison to the fluorescence radiance level of sound enamel. Changes in
      fluorescence radiance and lesion area can be followed in time to measure lesion
      development. The amount of fluorescence radiance loss is related to the mineral
      loss in the lesion. The technique can be used in vitro, in situ and in vivo to
      monitor mineral changes in lesions. Applications of QLF are found in the testing
      of products designed to inhibit demineralization and promote remineralization of
      caries. The method has been successfully applied to smooth surfaces as well as
      occlusal surfaces, but application on approximal lesions is not yet possible.

PMID- 10949840
TI  - Characterization and validation of diagnostic methods.
AB  - Diagnosis is defined as the determination of disease, but not as the
      determination of the signs and symptoms thereof. The use of modern diagnostic
      methodology in the clinic is hampered by cost considerations and by the still
      widespread belief that, e.g. caries lesions and periodontal breakdown are
      irreversible processes that need to be detected and treated invasively as early
      as possible, their measurement thus being irrelevant. Modern instrumental and
      quantitative methods allow early detection and introduction of noninvasive
      preventive measures to control the development of the disease. Such methods are
      also very beneficial in clinical research as they may describe the speed of
      progress or regress of disease. In epidemiology, such methods reduce the
      classical problem of calibration of observers. Repeatability, reproducibility,
      accuracy and validity are defined as method-characterizing quantities, for which
      examples are given. To express the validity of quantitative methods compared with
      a quantitative gold standard, the use of scatter plots and correlation and
      regression methods is suggested. Validation of a dichotomous method with a
      dichotomous gold standard in terms of sensitivity and specificity is discussed.
      To validate a quantitative method with a dichotomous gold standard, the receiver
      operating characteristic curve is suggested, with the requirement that the cutoff
      value should be determined in relation to the use of the method. However,
      preferably a quantitative method should not be reduced to a dichotomous one by
      using a cutoff value, but instead all available information should be used by the
      diagnostician. It is argued that the use of a secondary standard instead of the
      accepted gold standard usually leads to inadequate results, even when the
      validity of the secondary standard is known. Finally, it is argued that the
      choice of a gold standard is a matter of reasoning and weighing of arguments and
      not of following a prescribed procedure.

PMID- 10949841
TI  - Comparison of the in vitro activity of pristinamycin and
      quinupristin/dalfopristin against Streptococcus pneumoniae.
AB  - The in vitro activity of quinupristin/dalfopristin, a new injectable
      streptogramin, and pristinamycin was evaluated against 200 recently isolated
      clinical Streptococcus pneumoniae strains expressing various degrees of
      susceptibility to penicillin G and erythromycin. MICs were determined by the agar
      dilution method. All strains were susceptible to pristinamycin irrespective of
      their susceptibility to penicillin G or erythromycin (MIC90: 0.25 mg/L for each
      phenotype). The activity of quinupristin/dalfopristin was slightly lower than
      that of pristinamycin against 42 penicillin G-susceptible/erythromycin
      susceptible strains (MIC90: 0.5 mg/L), 13 penicillin G-susceptible/erythromycin
      resistant strains (MIC90: 1 mg/L), 25 penicillin G-intermediate or 
      resistant/erythromycin-susceptible strains (MIC90: 0.5 mg/L) and 120 penicillin G
      intermediate or -resistant/erythromycin-resistant strains (MIC90: 0.5 mg/L). The
      activity of both streptogramins was not significantly altered in case of
      erythromycin resistance. Thus, both streptogramins might be useful for the
      treatment of penumococcal infections, especially in cases of multiresistant
      strains.

PMID- 10949842
TI  - [Microbiological diagnosis of bacteremia from a catheter: a simple method?
      Results of a retrospective study].
AB  - Diagnosing catheter-related bloodstream infections is important but not always
      easy and a failure to make the diagnosis may have serious consequences. A high
      rate of unnecessary catheter removal is noted. We retrospectively compared the
      clinical and usual methods of microbiological diagnoses of catheter-related
      sepsis to the speed of detection of the catheter versus peripheral blood cultures
      using the Bact-Alert system. We analyzed 50 files of patients with central
      indwelling devices: 16 single lumen catheters and 34 implanted ports. Twenty-one
      catheters were classified as infected, and we observed an earlier positivity of
      catheter versus peripheral blood in all cases, but significant for 19 patients.
      According to standard diagnosis methods, 29 catheters were estimated non
      infected, a more rapid detection of peripheral culture was reported for 17
      specimens and, for another eight patients, the time of detection was equal to
      blood culture drawn from the catheter. In this group, four discrepancies were
      recorded with a differential time in favor of sepsis related to catheters ranging
      from 0.5 to 2 hours. Because of its simplicity and low cost, we believed that
      this method could be the first step of a diagnosis of catheter-related sepsis and
      could, therefore, avoid unjustified removal, in particular for the implanted
      ports for which the diagnostic methods are less codified than for catheters. A
      prospective study is ongoing; the design of the study focuses only on implanted
      ports.

PMID- 10949843
TI  - [Nitrofurans: a modern treatment for uncomplicated urinary infections?].
AB  - From January 1995 to December 1998, 2,912 strains of enteric bacilli were
      isolated from the urinary tract. Increasing antibiotic resistance in
      Enterobacteriaceae as a cause of urinary tract infection (UTI) led us to
      reevaluate first- and second-line therapies. We studied antimicrobial
      susceptibilities of these strains to norfloxacin (NOR), nalidixic acid (NAL),
      trimethoprim sulfamethoxazole (TS) and nitrofurantoin (FT) using the disk
      diffusion method. These results show no significant superiority of the activity
      of nitrofurantoin against Enterobacteriaceae compared with the other antibiotics
      with sustained concentration in urine. However, if we consider only
      multiresistant Enterobacteriaceae (cefotaxime resistant), this molecule appears
      to be very active. These results show a significant superiority of nitrofurantoin
      in vitro against these multiresistant Enterobacteriaceae. Thus, this molecule
      could once again become a good choice for the treatment of uncomplicated UTI.

PMID- 10949844
TI  - [Surveillance of Pseudomonas aeruginosa sensitivity to antibiotics in France and
      distribution of beta-lactam resistance mechanisms: 1998 GERPB study].
AB  - In a prospective study carried out during a three-week period in October 1998 in
      13 teaching hospitals, 735 non-repetitive isolates of Pseudomonas aeruginosa were
      collected. In patients presenting cystic fibrosis (70 strains), the main
      serotypes isolated were O:6 (14.3%) and O:1 (14.3%). Serotypes O:11 and O:12 were
      exceptional. In other patients (665 strains), the most frequent serotypes were
      O:6 (15.9%), O:11 (15.6%), O:1 (10.7%) and O:12 (9.2%). The antibiotic
      susceptibility rates were as follows (respectively, non-cystic fibrosis and
      cystic fibrosis strains): ticarcillin, 55 and 59%, piperacillin, 71 and 67%,
      ceftazidime, 75 and 67%, cefepime, 56 and 43%, cefpirome, 37 and 21%, aztreonam,
      57 and 56%, imipenem, 83 and 70%, amikacin, 69 and 33%, ciprofloxacin, 56 and 61%
      and fosfomycin, 33 and 43%. Serotype O:12 was the least susceptible to
      antibiotics. Forty-five percent of the non-cystic fibrosis strains presented
      intermediate susceptibility or resistance to ticarcillin. The most frequent
      mechanisms of resistance were: non-enzymatic resistance (14.3%), overproduction
      of the constitutive cephalosporinase (13.8%), production of transferable beta
      lactamase (8.6%) and a combination of these mechanisms (4.2%). Among cystic
      fibrosis strains, resistance to beta-lactam antibiotics was mainly due to
      overproduction of the constitutive cephalosporinase (18.6%), whereas production
      of a transferable beta-lactamase was rare (1.4%). Susceptibility to
      aminoglycosides and fluoroquinolones was less frequent in isolates producing
      transferable beta-lactamases and/or overproducing cephalosporinase. Decreased
      susceptibility to imipenem was more frequent in strains presenting a high level
      of cephalosporinase production. Among the cephalosporins, cefepime was the least
      affected by the overproduction of constitutive cephalosporinase. Ceftazidime
      remained the most efficient antibiotic against both susceptible isolates and
      strains presenting a non-enzymatic or PSE-1 penicillinase-producing mechanism.

PMID- 10949845
TI  - [Bacterial growth delay in E. coli: demonstration and evaluation of the beta
      lactamase post-inhibitor effect on 6 strains with different resistance
      phenotypes].
AB  - Six E. coli, whose phenotypes of resistance were different, were tested in vitro
      in order to evaluate a regrowth delay, the post beta-lactamases inhibitor effect
      (PLIE). This PLIE was investigated after a brief incubation in contact with
      clavulanic acid (CA) alone or associated with amoxicillin (AMX). After removal of
      the drugs used during the pre-exposure phase, the bacteria were incubated with
      AMX at different concentrations. The PLIE was shown not to be in association with
      any other regrowth delay (post-antibiotic effect or effect inherent to the
      technical procedures used). A PLIE was evaluated on the five intermediary or high
      level beta-lactamases-producing strains. Generally, the duration of the PLIE was
      prolonged after the CA alone pre-exposure phase and could reach values up to 22
      hours. The concentrations of AMX added in cultures previously exposed to
      sufficient CA concentrations were related to an extended PLIE.

PMID- 10949846
TI  - [Antibiotic sensitivity of enterobacteria in intensive care units].
AB  - Antibiotic therapy of intensive care patients is usually undocumented. The
      treatment is chosen according to epidemiologic and susceptibility data from
      microbiological laboratories. The aim of our study is to determine antibiotic
      susceptibility of enterobacteria isolated from intensive care patients during a
      five-month multicenter study in 18 French hospitals. Numerous (n = 1,113) strains
      were studied: 447 enterobacteria isolated from urine (n = 229), blood cultures (n
      = 106), respiratory tract specimens (n = 72), peritoneal fluids (n = 22), pus (n
      = 15) and catheters (n = 2). MICs of group 2 and group 3 enterobacteria were
      determined using the dilution agar method and were interpreted according to the
      CASFM (Comite de l'antibiogramme de la societe francaise de microbiology)
      recommendations. Group 1 enterobacteria were most frequently isolated (67%). Only
      one Escherichia coli strain produced ESBL (0.3%). Among group 2 enterobacteria,
      one Citrobacter koseri strain produced ESBL. We did not isolate Klebsiella
      pneumoniae ESBL. Isolation of group 3 enterobacteria was frequent (24%). Thirty
      five percent of group 3 enterobacteria were resistant to cefotaxime, 26% to
      ceftazidime and 16% to cefepime and cefpirome. Fourteen strains of this group
      produced ESBL: 13 Enterobacter aerogenes and one E. amnigenus.

PMID- 10949847
TI  - [Evaluation of the effect of early and massive tritherapy on the expression of
      cellular factors potentially implicated in antiretroviral therapy resistance].
AB  - Treatment of the human immunodeficiency virus (HIV) is restricted by therapeutic
      escape. The biological mechanisms of this chemoresistance rely notably on the
      modulation of cell kinase and P-glycoprotein (P-gp) expression. In this study, we
      investigated, in cynomolgus macaques, the roles of SHIV89.6P infection and of
      HAART in the mRNA expression of these cell factors. SHIV infection, or associated
      pathophysiological disorders, increase both thymidine kinase and thymidylate
      kinase mRNA expression and decrease those of P-gp. On the other hand, the
      expression of other cell kinases is not modulated. In parallel, HAART accentuates
      the decrease of P-gp expression and attenuates the increase of kinase expression.
      On the whole, such metabolic disorders, evidenced herein an animal model of HIV
      infection, could be involved in HIV-infected patients.

PMID- 10949848
TI  - [Mycobacterium avium complex disease in HIV seropositive patients: incidence and
      risk factors before and after the introduction of highly active antiretroviral
      treatments. Clinical Epidemiology Group of the Information and Care Center for
      Human Immunodeficiency].
AB  - The objective of this study was to determine the risk factors of the first
      occurrence of Mycobacterium avium complex disease (MAC) infection among human
      immunodeficiency virus (HIV)-infected subjects during two different time periods:
      before and after the introduction of protease inhibitor (respectively, period 1:
      1 January 1992 to 31 December 1995, and period 2: 1 January 1996 to 30 June
      1998). This study was performed using the French Hospital Database on HIV (FHDH).
      Subjects were included when their CD4+ cell count was less than 100/mm3. If they
      did not die or develop MAC within the first 6 months after the inclusion, their
      follow-up had to be longer than 6 months to be included. Cox's model was used to
      calculated the relative hazards (RH) of MAC occurrence according to the age and
      time-dependent variables, such as CD4+ below 50/mm3, previous occurrence of
      tuberculosis, cytomegalovirus (CMV) infection and other acquired immunodeficiency
      syndrome (AIDS)-defining disease, nature of antiretroviral treatment and MAC
      prophylaxis. Among the 14,779 subjects followed during period 1, 1,710 (11.6%)
      had a diagnosis of MAC infection during their follow-up (incidence: 8.4 +/- 0.2
      for 100 persons per year), while only 453 (4.4%) among 10,239 subjects presented
      this infection during period 2 (2.8 +/- 0.1 for 100 persons per year). Rifabutin
      regular prescription was a protective factor of MAC occurrence during period 1
      (RH = 0.51 95% confidence interval (CI) = [0.37-0.69]), whereas this protective
      effect was not observed during period 2 (RH = 1.05 CI = [0.63-1.67]). Thus,
      during the HAART period, the results that we present do not indicate an interest
      into continuing MAC prophylaxis.

PMID- 10949849
TI  - [Fatal lactic acidosis in a patient infected by HIV and treated with stavudine
      and didanosine].
AB  - We report a case of severe lactic acidosis in an human immunodeficiency virus
      (HIV)-infected patient treated with combination regimen of stavudine, didanosine
      and nevirapine. Antiretroviral nucleoside analogs are inhibitors of mitochondrial
      DNA polymerase gamma, resulting in the dysfunction of the mitochondrial
      respiratory chain. Despite symptomatic treatments and intravenous L-carnitine
      supplementation, lactic acidosis persisted, leading to multiorgan failure. The
      patient died 7 days after admission to the intensive care unit. Retrospective
      analysis of published cases showed neither specific nor predictive signs of
      outcome that is usually fatal, with no effective therapy to date. We therefore
      recommend determining blood lactate in patients with onset of unexplained general
      fatigue or digestive signs and to stop all antiretroviral treatments in the case
      of lactate increase.

PMID- 10949850
TI  - [Conditions of "thymidine analog mutations" (TAMs) in naive patients treated with
      different combinations of d4T].
AB  - Recently, d4T/ddI combination has been associated with the selection of thymidine
      analogue mutations (TAMs) in 50% of patients with a detectable viral load after 6
      to 12 months of this bi-therapy (ALBI, STADI and BMS A1460 tests). We evaluated
      the rate of selection of the TAMs in naive patients with a viral load of > 200
      copies/mL after: 6 months to 1 year of d4T/3TC bi-therapy (group 1); 1 year or
      more of a treatment including d4T/3TC (group 2); and more than 6 months of tri
      therapy including d4T/ddI (group 3). The reverse transcriptase gene has ben
      studied in 33 patients in group 1, 17 patients in group 2 and ten patients in
      group 3. For the latter patients, the tri-therapies were as follows: d4T/ddI/PI
      (n = 5), d4T/ddI/NNRTI (n = 4), d4T/ddI/NRTI (n = 1). For the group 1 patients,
      at baseline, two patients already had TAMs. At M6, all the patients acquired the
      3TC-associated mutations, M184V. Only one patient selected a MDR mutation profile
      (F116Y, Q151M). At M12, 26 of 33 plasmas were analysed. Only one patient selected
      one TAM (T215Y). For the group 2 patients, only three patients selected TAMs
      after more than 30 months of treatment. For the group 3 patients, at baseline,
      only one patient already harbored TAMs. None of the other patients had selected
      TAMs. In patients who received d4T/ddI/3TC, only the M184V, the 3TC-associated
      mutation, was selected. In conclusion, stavudine in association with 3TC selected
      a low rate of TAMs; in patients receiving a treatment including d4T/3TC, time of
      exposure to stavudine seemed to be an important parameter for the selection of
      TAMs; and in contrast to results obtained on d4T/ddI, tri-therapies including
      d4T/ddI did not select any TAMs, whatever the combination (NRTI, NNRTI, PI).

PMID- 10949851
TI  - [Antiretroviral ant anti-inflammatory properties of a novel platelet activation
      factor antagonist, PMS-601].
AB  - The platelet-activating factor (PAF) plays a major role in neuropathogenesis
      associated with human immunodeficiency virus (HIV) infection by enhancing the
      inflammatory syndrome and viral replication, particularly in cells of the
      macrophage lineage, and its neurotoxic properties. We therefore evaluated the
      ability of PAF-R antagonists to inhibit HIV-1 replication and down-modulate the
      synthesis of pro-inflammatory mediators in healthy or HIV-1-infected macrophages.
      PMS-601 demonstrated the highest anti-HIV activity. Considering its mode of
      action and anti-inflammatory properties, PMS-601 interferes with early and late
      steps of the HIV biological cycle and decreases the synthesis of PAF, TNF-alpha,
      MIP-1 alpha, MIP-1 beta and RANTES. Altogether, these results suggest that PAF
      receptor antagonists, and particularly PMS-601, could be of potential value as
      treatment adjuvants in HIV infection.

PMID- 10949852
TI  - A survey of different successful microsurgical vascular prostheses in animal
      experiments.
AB  - The authors summarize historical findings from the literature on the success of
      microsurgical vascular prostheses in experimental practice with regard to
      different production and construction technologies. They reference authors and
      surgeons using Gore-Tex, polyurethane, polyactide, silicone and woven vascular
      microprostheses.

PMID- 10949853
TI  - Woven vascular microsurgical prostheses in our experimental practice.
AB  - The authors have been concerned for six years with the development of woven
      microsurgical prostheses in experiments on laboratory rats, beagle dogs and
      domestic white pigs. In rats, in 224 experiments employing 38 types of prostheses
      with an inner diameter of 2 mm, a reliable prosthesis was selected, described as
      No. 36, with a 100% patency after insertion of a 1 cm long portion into a defect
      in the abdominal aorta in 40 experiments. The follow-up of this type of
      prosthesis lasted 12 months. In large animals this type of prosthesis was
      implanted into a defect of the radial artery and cephalic vein in dogs and into
      the femoral artery and the artery of a vascular pedicle of groin and lateral
      thigh flap. These experiments on large animals are not yet complete and will be
      the subject of a separate paper.

PMID- 10949854
TI  - Evaluation of results of replantations at the Department of Plastic Surgery,
      University Hospital Kralovske Vinohrady, during the period 1994-1999.
AB  - During the period from 1994-1999, 226 patients were treated, incl. 91
      replantations and 135 revascularizations. The group included 199 men and 27
      women. The success rate of microsurgical reconstruction operations in
      replantations was 78%, in revascularizations 93%. As compared with the period
      1984-1993, the success rate in replantations improved by 4%, while the indication
      pattern was preserved.

PMID- 10949855
TI  - Arteriovenous malformations of the orofacial area.
AB  - Vascular lesions are pathological residues of the embryonic vascular system and
      can be divided into two main groups. The first group comprises haemangiomas,
      which are typical of childhood and involute spontaneously. The second group is
      formed by lesions without active proliferation, which include, among others,
      arteriovenous malformations that are congenital and grow proportionately with the
      subject. The authors present two cases of arteriovenous malformations of the
      orofacial area and discuss possibilities for modern diagnosis and treatment.
      Precise diagnosis and effective treatment of vascular lesions should be ensured
      by a diagnostic and therapeutic team of specialists from several disciplines
      (maxillofacial, ENT, plastic and general surgeon, paediatrician, haematologist,
      anaesthesiologist and possibly a neurosurgeon), headed by an intervention
      radiologist.

PMID- 10949856
TI  - Lethal burn trauma in children.
AB  - The aims of this retrospective study covering the years 1984-1998 were: 1. to
      survey burn injuries in children at the present time and 2. to compare the
      current results with the conclusions of an analogous study performed in the years
      1964-1983. A decline in the occurrence of lethal burn wounds was found, as well
      as in burn shock as a direct cause of death. Children 1-4 years old continue to
      be the most frequent victims of fatal accidents. The most common cause of burn
      injury in this group remains scalding in the household.

PMID- 10949857
TI  - Burn wound coverage and burn wound closure.
AB  - Early excision and grafting changed dramatically topical wound treatment, but are
      restricted by difficulty in diagnosing burn depth, by limited donor sites and by
      technical skills to excise special areas (perineum, face). In addition to the
      extent of burn and the age of the patient the depth is determinant of mortality,
      morbidity and of patient's quality of life. It results from the time-temperature
      relation and is further influenced by local and systemic causes of conversion:
      dehydration, edema, infection and shock hypoxia, metabolic derangements,
      peripheral vessels diseases may contribute do deepening of burn wound.
      Superficial burn on day one appears deep dermal by day three, where spontaneous
      epithelization lasts much longer than 21 days and results in hypertrophic
      scarring. To prevent this sequelae deep dermal burn may be treated like full
      thickness injury with excision and autografting. Another way is removal of dead
      layers of corium and using biological or synthetic cover. We have found a more
      effective way to reach wound closure (not only cover) in the method of "upside
      down" application of recombined human/pig skin (RHPS), composed of allogeneic
      human keratinocytes cultured on cell-free pig dermis. The allogeneic epidermal
      cells temporarily "take", "close" the excised wound and simultaneously encourage
      epithelization from adnexa remnants in the wound bed. Thus definitive closure is
      achieved.

PMID- 10949858
TI  - Predictive inference, causal reasoning, and model assessment in nonparametric
      Bayesian analysis: a case study.
AB  - This paper continues our earlier analysis of a data set on acute ear infections
      in small children, presented in Andreev and Arjas (1998). The main goal here is
      to provide a method, based on the use of predictive distributions, for assessing
      the possible causal influence which the type of day care will have on the
      incidence of ear infections. A closely related technique is used for the
      assessment of the nonparametric Bayesian intensity model applied in the paper.
      Two graphical methods, supported by formal tests, are suggested for this purpose.

PMID- 10949859
TI  - A comparison of frailty and other models for bivariate survival data.
AB  - Multivariate survival data arise when each study subject may experience multiple
      events or when study subjects are clustered into groups. Statistical analyses of
      such data need to account for the intra-cluster dependence through appropriate
      modeling. Frailty models are the most popular for such failure time data.
      However, there are other approaches which model the dependence structure
      directly. In this article, we compare the frailty models for bivariate data with
      the models based on bivariate exponential and Weibull distributions. Bayesian
      methods provide a convenient paradigm for comparing the two sets of models we
      consider. Our techniques are illustrated using two examples. One simulated
      example demonstrates model choice methods developed in this paper and the other
      example, based on a practical data set of onset of blindness among patients with
      diabetic Retinopathy, considers Bayesian inference using different models.

PMID- 10949860
TI  - Standardized martingale residuals applied to grouped left truncated observations
      of dementia cases.
AB  - The use of martingale residuals have been proposed for model checking and also to
      get a non-parametric estimate of the effect of an explanatory variable. We apply
      this approach to an epidemiological problem which presents two characteristics:
      the data are left truncated due to delayed entry in the cohort; the data are
      grouped into geographical units (parishes). This grouping suggests a natural way
      of smoothing the graph of residuals which is to compute the sum of the residuals
      for each parish. It is also natural to present a graph with standardized
      residuals. We derive the variances of the estimated residuals for left truncated
      data which allows computing the standardized residuals. This method is applied to
      the study of dementia in a cohort of old people, and to the possible effect of
      the concentration of aluminum and silica in drinking water on the risk of
      developing dementia.

PMID- 10949861
TI  - Nonparametric survival estimation when death is reported with delay.
AB  - In disease registries there can be a delay between death of a subject and the
      reporting of this death to the data analyst. If researchers use the Kaplan-Meier
      estimator and implicitly assumed that subjects who have yet to have death
      reported are still alive, i.e. are censored at the time of analysis, the Kaplan
      Meier estimator is typically inconsistent. Assuming censoring is independent of
      failure, we provide a simple estimator that is consistent and asymptotically
      efficient. We also provide estimates of the asymptotic variance of our estimator
      and simulations that demonstrate the favorable performance of these estimators.
      Finally, we demonstrate our methods by analyzing AIDS survival data. This
      analysis underscores the pitfalls of not accounting for delay when estimating the
      survival distribution and suggests a significant reduction in bias by using our
      estimator.

PMID- 10949862
TI  - Intrinsic priors for model selection using an encompassing model with
      applications to censored failure time data.
AB  - In Bayesian model selection or testing problems one cannot utilize standard or
      default noninformative priors, since these priors are typically improper and are
      defined only up to arbitrary constants. Therefore, Bayes factors and posterior
      probabilities are not well defined under these noninformative priors, making
      Bayesian model selection and testing problems impossible. We derive the intrinsic
      Bayes factor (IBF) of Berger and Pericchi (1996a, 1996b) for the commonly used
      models in reliability and survival analysis using an encompassing model. We also
      derive proper intrinsic priors for these models, whose Bayes factors are
      asymptotically equivalent to the respective IBFs. We demonstrate our results in
      three examples.

PMID- 10949863
TI  - Estimation of distribution functions using data from different environments.
AB  - Suppose that when a unit operates in a certain environment, its lifetime has
      distribution G, and when the unit operates in another environment, its lifetime
      has a different distribution, say F. Moreover, suppose the unit is operated for a
      certain period of time in the first environment and is then transferred to the
      second environment. Thus we observe a censored lifetime in the first environment
      and a failure time of a "used" unit in the second environment. We propose an EM
      algorithm approach for obtaining a self-consistent estimator of F using
      observations from both environments. The case where failure times are subject to
      right censoring is considered as well. We also establish the maximum likelihood
      estimator of F when the unit is repairable. Application and simulation studies
      are presented to illustrate the methods derived.

PMID- 10949864
TI  - Optimal tests for no contamination in reliability models.
AB  - Inferences on mixtures of probability distributions, in general, and of life
      distributions, in particular, are receiving considerable importance in recent
      years. The likelihood ratio procedure of testing for the null hypothesis of no
      contamination is often very cumbersome and lacks its usual asymptotic properties.
      Recently, SenGupta (1991) has introduced the notion of an 'L-optimal' test for
      such testing problems. The idea is to recast the original several parametric
      hypotheses representation of the null hypothesis in terms of only a single
      hypothesis involving an appropriately chosen parametric function. This approach
      is shown to be both mathematically elegant and operationally simple for a quite
      general class of mixture distributions which contains, in particular, all
      mixtures of the one-parameter exponential family and also a very rich subclass of
      mixtures useful in life-testing and reliability analysis. It is also illustrated
      through two examples--one based on real-life data and the other on a simulated
      sample.

PMID- 10949865
TI  - Use of induced sputum in the diagnosis and follow-up of asthma and chronic
      obstructive pulmonary disease.

PMID- 10949866
TI  - Respiratory responses to chemical stimulation in patients with obstructive sleep
      apnoea.
AB  - Chemical control of breathing in obstructive sleep apnoea (OSA) patients has been
      studied by many authors. The results of previous studies, especially those
      dealing with hypoxic drive, are discordant. Respiratory responses were studied
      during hypercapnic and hypoxic stimulation in a group of 37 normocapnic patients
      with OSA during wakefulness. The diagnosis of OSA was established by standard
      polysomnography. These patients had increased apnoea/hypopnoea index (AHI; 51 +/-
      22 (mean +/- SD)), obesity (body mass index (BMI) 32.4 +/- 5.6 kg.m-2) and normal
      lung function tests. The control group consisted of 14 healthy obese subjects
      (BMI 31.2 +/- 3.3 kg.m-2). Respiratory responses (ventilatory and mouth occlusion
      pressure (P0.1)) during hypercapnic and hypoxic rebreathing tests were measured
      with the use of computerized equipment. Respiratory responses during hypercapnic
      stimulation were similar to those in the control group (change in (delta) minute
      ventilation (V'E)/delta carbon dioxide tension (PCO2) 23.5 +/- 14.8 versus 22.3
      +/- 10.0 L.min-1.kPa-1, delta P0.1/delta PCO2 4.6 +/- 3.6 versus 4.2 +/- 2.6
      cmH2O.kPa-1). During isocapnic hypoxic stimulation in OSA patients the mean
      ventilatory response was higher than in the control group (delta V'E/delta
      arterial oxygen saturation (Sa,O2) 2.6 +/- 1.7 versus 1.7 +/- 0.7 L.min-1.%-1)
      but this difference was not statistically significant. Nevertheless, it was found
      that 13 (35%) OSA patients had increased ventilatory responses. The mean P0.1
      response in OSA patients was higher but did not differ significantly from those
      in the control group (delta P0.1/delta Sa,O2) 0.43 +/- 0.38 versus 0.35 +/- 0.12
      cmH2O.%-1). The results demonstrated that respiratory responses to chemical
      stimulation in awake normocapnic patients with obstructive sleep apnoea were in
      the normal range, similar to those in control obese subjects. During hypoxic
      stimulation some of them had increased ventilatory (35%) and mouth occlusion
      pressure (16%) responses.

PMID- 10949867
TI  - Prevalence, age distribution and aetiology of bronchiectasis: a retrospective
      study on 144 symptomatic patients.
AB  - The incidence of bronchiectasis (BCT) has probably decreased in developed
      countries in recent years, but reliable statistical data on its occurrence are
      still lacking. The aim of the present study was to retrospectively evaluate the
      prevalence, age distribution and aetiology of BCT, diagnosed in a selected series
      of symptomatic patients of a Western country by using bronchography. The authors
      analysed the main known predisposing and associated conditions (PACs), and the
      occurrence and age distribution of BCT in 144 consecutive patients who underwent
      bronchological examination (fibreoptic bronchoscopy and bronchography) in the
      years 1987-1994 because of recurrent purulent bronchitis and/or haemoptysis. The
      overall prevalence of BCT was 34% (49/144); its age distribution was: 17.2% (0-10
      yrs), 43.7% (11-20 yrs), 38% (21-30 yrs), 37.5% (31-40 yrs), 33.3% (41-50 yrs),
      40% (51-60 yrs), and 20% (61-70 yrs). Thirty-one PACs were found in 29/144
      patients of the whole study group. The prevalence of BCT was significantly higher
      in the subgroup of 29 patients with PACs than in the subgroup of 115 patients
      without PACs (75.9% versus 23.5%; p < 0000001). The aetiology of BCT was mainly
      unexplained, as it was only possible to detect 24 PACs in 22/49 patients with BCT
      (44.9%): congenital, genetic and immune disorders (eight), localized airways
      obstructive diseases (five), pulmonary infections (three), bronchial asthma
      (two), pulmonary lobar fibrosis (two), ulcerative colitis (two), dermatomiositis
      (one), and toxin inhalation (one). The authors conclude that bronchiectasis still
      occurs in a large percentage of symptomatic patients of a developed country in
      the post-antimicrobial era, especially in the second to sixth decades, as well as
      in the presence of predisposing and associated conditions; its aetiology remains
      unknown in more than half of cases.

PMID- 10949868
TI  - Computerized impedance plethysmography in the diagnosis of delayed deep vein
      thrombosis after total hip replacement.
AB  - Although noninvasive techniques have been extensively evaluated in the diagnosis
      of deep vein thrombosis (DVT), few data exist about the role of computerized
      impedance plethysmography (CIP) in the diagnosis of delayed DVT after surgery,
      when patients are at home and the risk of DVT is still high. The aim of this
      study was to evaluate the reliability of CIP in the diagnosis of proximal and
      distal delayed DVT in both symptomatic and asymptomatic patients who had
      undergone elective total hip replacement (THR). Bilateral CIP of lower limbs was
      performed in 61 patients on days 5, 9, 15 and 45 after THR; for comparison,
      ascending phlebography was performed on days 45 after THR in all patients on the
      operated limb or on the limb with positive results on CIP. The overall rate of
      DVT diagnosed by phlebography was 16.3% (10/61). The sensitivity and specificity
      of CIP for all DVT were 20% and 98%, respectively, while the accuracy was 85%.
      The results were not influenced by the presence of symptoms or signs of the lower
      limbs. Similar results were obtained when considering proximal DVT only. In
      conclusion, the low sensitivity of computerized impedance plethysmography means
      that it cannot be used in screening for delayed deep vein thrombosis after total
      hip replacement, in both symptomatic and asymptomatic patients. However, because
      of its high specificity, when the results of computerized impedance
      plethysmography are positive phlebography should be performed to confirm the
      diagnosis of deep vein thrombosis.

PMID- 10949869
TI  - HHV-8 is not a cofactor in the pathogenesis of environmentally induced malignant
      pleural mesothelioma.
AB  - After the recognition of human herpes virus 8 (HHV-8) in Kaposi's sarcoma
      lesions, this new virus has been shown to be associated with various types of
      malignancy. One of them, body cavity-based lymphoma, is a high grade B-cell
      lymphoma arising from the body cavities. Similarly, mesothelioma is a tumour that
      originates from the serosal linings of the pleural, pericardial and peritoneal
      cavities. One of the striking characteristics of mesothelioma cells is the
      secretion of interleukin-6 (IL-6). Also, it is known that HHV-8 upregulates the
      levels of IL-6, and this virally originated IL-6 is a well-established growth
      factor for HHV-8-associated lesions. Therefore, it was hypothesized that HHV-8
      may have a role in the pathogenesis of malignant mesothelioma. Twenty-nine
      pleural biopsy specimens from environmentally induced malignant mesothelioma
      patients were investigated for the presence of HHV-8 deoxyribonucleic acid (DNA)
      using the polymerase chain reaction (PCR). Control pleural samples were collected
      from 15 biopsy specimens from patients with tuberculosis. From all samples, a
      segment of the beta-globulin gene was amplified in order to make sure that the
      DNA was extracted properly and did not contain any inhibitors. The specificity of
      the PCR amplification was confirmed by means of restriction enzyme analysis using
      Providencia stuartii I. PCR did not reveal HHV-8 DNA in any of the mesothelioma
      patients or in the control group. It was possible to amplify a segment of the
      human beta-globulin gene from all the samples of the patient and control groups.
      HHV-8 DNA was amplified in the control sample, which was a tissue biopsy specimen
      from a Kaposi's sarcoma lesion, and it was confirmed that the amplified DNA
      belonged to HHV-8 by restriction enzyme analysis. Malignant mesothelioma
      continues to be a public health problem in rural parts of Anatolia, Turkey. The
      major causal factor of the disease is exposure to asbestos and fibrous zeolite
      (erionite). It seems that there must be some aetiological factors other than
      exposure to these minerals as not all patients exposed to asbestos develop the
      disease and the disease is not always associated with any known exposure. From
      the present study, it was concluded that human herpes virus 8 does not seem to be
      associated with environmentally induced malignant mesothelioma in Turkey. Other
      possible causal factors of malignant mesothelioma should be sought.

PMID- 10949870
TI  - Long-term survival in primary amyloidosis of the laryngotracheobronchial tract by
      treating complications only.
AB  - Primary amyloidosis limited to the laryngotracheobronchial tract is relatively
      uncommon; therefore, knowledge of survival in these patients is poor and
      consensus regarding appropriate therapy unreached. The case is reported of a
      patient affected by primary amyloidosis limited to the laryngotracheobronchial
      tract who had a long survival and a good quality of life after only medical and
      neodymium-yttrium aluminium garnet (Nd-YAG) laser therapy. The patient had
      amyloidosis first detected in the larynx, which, 4 yrs later, progressed to
      involve the tracheobronchial tract, without pulmonary involvement. The patient
      was treated three times with Nd-YAG laser to obtain the recanalization of
      obstructed bronchi, with evident improvement of symptoms and pulmonary function.
      In conclusion, laryngotracheobronchial amyloidosis survival may be lengthened and
      quality of life made more acceptable by treating potential complications only.

PMID- 10949872
TI  - Hypertrophic osteoarthropathy in lung cancer: are the radiographic bone changes
      reversible after curative resection?
AB  - Lack of relief of bone and joint pains and persistence of the radiographic
      abnormalities in patients with secondary hypertrophic osteoarthropathy, after
      lung tumour removal, are considered as signs of an unfavourable prognosis. Two
      patients are documented in whom the lack of reversion of periosteal changes after
      tumour removal was compatible with a favourable long-term prognosis, suggesting
      that radiographic exploration is an insensitive technique to appreciate
      involutive bone changes occurring in these patients.

PMID- 10949871
TI  - Tuberculous pneumonia complicating lung transplantation: case report and review
      of the literature.
AB  - Although tuberculosis is more common in transplant recipients than in the general
      population, most centres report that mycobacterial infection is very rare in
      comparison with the extreme variety of transplant-associated infections. Only 18
      previous cases of tuberculosis-complicated lung or heart-lung transplants have
      been published. An unusual case is reported of Mycobacterium tuberculosis
      infection in a double-lung recipient who presented a radiographic feature of
      segmental pneumonia, mimicking a bacterial infection. Bronchoalveolar lavage
      revealed lymphocytosis (> 30% of isolated cells). Data regarding optimal
      treatment for tuberculosis in lung transplant recipients are limited.
      Nevertheless, therapy should not be different from that in other
      immunocompromised patients and should include an aggressive initial four-drug
      regimen (until the sputum cultures become negative) or a 6-month conventional
      therapy with two agents to which the organism is susceptible. Close follow-up is
      required to confirm the bacteriological response and minimize the likelihood of
      relapse. In this patient, treatment with a four-drug antituberculous regimen for
      3 months followed by isoniazide and rifampicin for an additional 9 months was
      curative.

PMID- 10949873
TI  - Pathology of emphysema in chronic obstructive pulmonary disease.
AB  - Emphysema is an almost constant finding in the lungs of chronic obstructive
      pulmonary disease patients. Several types of emphysema are recognized by
      pathologists, but only the centrilobular (CLE) and panlobular (PLE) emphysemas
      are found in association with smoking. In this review, the morphological and
      functional differences between CLE and PLE are described, and it is suggested
      that they could arise as different abnormalities as a result of the same insult,
      cigarette smoke. In CLE: 1) the destruction of the lung is uneven and originates
      around the airways; 2) the membranous bronchioles are thicker, narrower and more
      reactive than in PLE; 3) lung compliance is low or normal and does not relate to
      the extent of the emphysema; and 4) the decrease in flow is related mainly to the
      degree of airway abnormality and not to the losses of elastic recoil. In
      contrast, in PLE: 1) the destruction of the lung is even; 2) the small airways
      appear less narrowed and less inflammed than in CLE; 3) the compliance of the
      lung is increased and related to the extent of the emphysema; and 4) the decrease
      in flow is related mainly to the loss of elastic recoil and not to the
      abnormalities in the airways. The authors would propose that centrilobular
      emphysema and panlobular emphysema are distinct entities, centrilobular emphysema
      an airborne disease related to airway reactivity, panlobular emphysema a blood
      borne disease related to abnormalities in lung protective mechanisms against
      inflammatory insults.

PMID- 10949874
TI  - Home-based rehabilitation for patients with COPD: organization, effects and
      financial implications.
AB  - Rehabilitation in patients with chronic obstructive pulmonary disease (COPD) has
      been shown to be an effective treatment and can be carried out in different
      settings, i.e. inpatient, outpatient or home-based. This review focuses on home
      based rehabilitation and four important issues are discussed. 1) Which patients
      should received home-based rehabilitation? 2) How should home-based
      rehabilitation be organized? 3) What are the effects of home-based
      rehabilitation? 4) What are the financial implications. Home-based rehabilitation
      is an attractive approach for most patients with COPD. However, there is some
      evidence that patients who are severely disabled due to dyspnoea do not gain
      benefit from home-based rehabilitation. This might not be the appropriate setting
      for this group, and these patients are probably better candidates for an
      inpatient or outpatient multidisciplinary approach. After initial evaluation of
      the patient by a pulmonary physician, home-based rehabilitation can be set up in
      two different ways. Firstly, the patients can receive their instructions at the
      hospital: a detailed exercise programme can be developed that the patients can
      perform unsupervised at home with regular follow-up at the outpatient clinic.
      Second, home rehabilitation can be fully addressed at home with instruction and
      regular supervision by a local team. At this moment, it is not clear which
      disciplines, i.e. what kinds of intervention, are needed in a home rehabilitation
      team. Nevertheless, the key element of home-based rehabilitation is exercise
      training, which is the same for the other settings. Short-term studies with a
      maximum duration of 12 weeks showed increased exercise tolerance, decreased
      dyspnoea and improved quality of life. Conversely, the effects of long-term home
      based rehabilitation are not clearly established. The need for long-term
      supervision is still open to debate: contradictory results have been shown
      regarding dyspnoea and exercise tolerance. Cost/benefit analysis showed positive
      trends in reduction in hospitalization rate and reduction of total costs;
      however, these results came from uncontrolled studies.

PMID- 10949875
TI  - How can ultrafine particles be responsible for increased mortality?
AB  - The link between particulate air pollution at relatively low levels and adverse
      effects both in the lungs and of the cardiovascular system remains a puzzling
      event. The authors have developed a hypothesis which suggests that ultrafine
      components of particulate air pollution may result in local and systemic
      oxidative stress, which produces lung inflammation, but also the systemic
      effects, resulting in mortality in susceptible individuals from cerebrovascular
      disease. Preliminary data in vitro and in vivo suggest that both local and
      systemic oxidative stress occur in response to ultrafine particles and that the
      effects of such oxidative stress on pro-inflammatory gene regulation and changes
      in blood coagulation may result in the adverse effects of particulate air
      pollution. In this article, the evidence which supports this hypothesis is
      reviewed.

PMID- 10949876
TI  - Bronchiolitis obliterans syndrome after lung transplantation: medical treatment.
AB  - Obliterative bronchiolitis (OB) or the clinical correlate bronchiolitis
      obliterans syndrome (BOS) is the main cause of late morbidity and mortality after
      heart-lung and lung transplantation. Although several risk factors for the
      development of OB/BOS have already been identified, very effective preventive
      therapy remains Utopian, although there has been much improvement in recent
      years. This paper attempts to summarize current experience in the medical
      treatment of OB/BOS, either by tackling the known risk factors for the
      development of OB/BOS or by changing the immunosuppressive drug regimen for
      treating established OB/BOS. The current treatment options, however, are rather
      anecdotal and mostly single-centre experiences. Therefore, multicentre studies
      are definitely needed to try to identify the most appropriate drug regimen either
      to prevent and to treat obliterative bronchiolitis/bronchiolitis obliterans
      syndrome.

PMID- 10949877
TI  - Viruses and idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis is an increasingly recognized problem with a poor
      prognosis. The aetiology remains unclear. However, many patients date the onset
      of their disease to a recent viral infection, implying that viruses may have a
      potential role in disease progression. A number of studies have suggested an
      association between idiopathic pulmonary fibrosis and viruses including
      adenovirus, Epstein-Barr virus and hepatitis C. However, the molecular techniques
      used in identifying the viruses are extremely sensitive and may lead to erroneous
      associations being made. This review attempts to place into context the
      identification and potential role of viruses in patients with idiopathic
      pulmonary fibrosis.

PMID- 10949878
TI  - Asbestos exposure, lung cancer and asbestosis.
AB  - The relationship between asbestos exposure, lung cancer and asbestosis is
      reviewed. Studies have demonstrated the risk of lung cancer to be raised in
      asbestos-exposed workers whether asbestosis is present or not. Although
      increasing exposure increases the risk of disease, variability in estimation of
      fibre levels and in subject susceptibility should be borne in mind. Consensus
      opinion recommends that attribution of lung cancer to asbestos exposure should be
      based on clinical and occupational histories. The risk of lung cancer in those
      who both smoke and are exposed to asbestos is increased in a multiplicative way,
      putting subjects at very great risk.

PMID- 10949879
TI  - Some memoranda on the diagnostic criteria of lung disease caused by Mycobacterium
      avium-Mycobacterium intracellulare complex.
AB  - The simultaneous appearance of new cavitary lesions in the lungs and two or more
      isolations of Mycobacterium avium-Mycobacterium intracellulare complex (MAC) by
      daily or monthly sputum examination in the initial few days or the initial 6
      months shows the presence of lung disease caused by MAC. Three isolations of MAC
      by three to six daily or monthly sputum examination confirms the occurrence of
      lung disease caused by MAC. These criteria and their basis were published by the
      present author in 1974 and 1978. The criteria are almost the same as those
      published by the American Thoracic Society in 1997.

PMID- 10949880
TI  - A possible mediator role for endothelin-1 in respiratory disease.
AB  - Endothelin (ET)-1 is an endogenous endothelium-derived peptide, long recognized
      as a potent vascular smooth muscle spasmogen and mitogen. Strong links have been
      made between these and other actions of ET-1 and vascular diseases including
      pulmonary hypertension. Importantly, it is also now established that ET-1 is
      synthesized in the airway epithelium and that it has a range of effects in the
      respiratory tract which suggest a significant mediator role in asthma. These
      actions include airway smooth muscle contraction, bronchoconstriction and
      proliferation, potentiation of cholinergic neuronal function, mucus
      hypersecretion of pro-inflammatory activities including the promotion of airway
      microvascular leakage and oedema. The following is a brief review of the actions
      of endothelin-1 that suggest a link between endothelin-1 and obstructive airway
      diseases such as asthma.

PMID- 10949881
TI  - Are anticholinergics first choice bronchodilators in the treatment of stable
      chronic obstructive pulmonary disease?

PMID- 10949882
TI  - [CD43 in B-cell chronic lymphocytic leukemia].
AB  - CD43 (other names: sialophorin, leukosialin, sialoglycoprotein of white blood
      cells) is an integral cell membrane mucin. In population of peripheral B cells
      CD43 occurs only on activated B cells and CD5 positive B cells. These last cells
      create neoplasm population in patients with B-cell chronic lymphocytic leukemia
      (B-CLL). Anti-CD43 monoclonal antibodies are used routinely in investigations of
      tissue fragments in cases of non-Hodgkin's lymphoma, whereas we did not find
      publication on theme of CD43 expression on peripheral blood B cells in patients
      with B-cell chronic lymphocytic leukemia. Wherefore advisable appeared estimation
      CD43 expression on B-CLL cells and comparison it with expression of typical B-CLL
      markers--such as CD5 and CD6. Immunological phenotype of peripheral blood and
      bone marrow lymphocytes has been evaluated using flow cytometry (Cytoron Absolute
      Ortho-Diagnostic Systems) and two-color staining. Twenty six untreated patients
      with B-CLL were studied. Because on well-known correlations between CD43
      expression and metastasis potential of tumor, patients were divided on two groups
      differing score of total tumor mass (score TTM). Score TTM was evaluated
      according to criterion of Jaksic and Vitale. Twelve patients whose TTM score was
      equal or lower than 9 and median lymphocytosis was 24.6 x 10(9) in microliter
      were included in group I. 14 patients whose TTM score was higher than 9 were
      included in group II. Median lymphocytosis in these patients was 152.6 x 10(9) in
      microliter. The median percentage of CD43+/CD19+ cells in peripheral blood was
      62.6% in the group I, and 75% in the group II (p < 0.05). Median fluorescence
      intensity (MFI) of CD43 antigen was 87.7 in the I group comparing to 77.4 in the
      group II. So one observed tendency to lowering MFI during tumor growing but the
      difference was not significant (p = 0.25). In peripheral blood during progression
      of disease more clearly than CD43+ cells increased percentage of CD5+ and CD6+
      cells. The median percentage of CD19+/CD5+ cells was 62.7% in the group I, 82.4%
      in the group II and the difference was significant (p < 0.002). The difference in
      the median percentages CD6+/CD19+ cell 71.8% in group I and 84.3% in the II one
      were also significant (p < 0.03). MFI of CD5 and also CD6 antigens did not change
      in course of disease. Moreover, examination of CD43 and CD5 expression in marrow
      additionally to blood study were performed in 12 cases (6 from group I, 2 from
      group II and 4 new not included). The median percentage of CD43+/CD19+ cell was
      35.1% in blood and 43.7% In marrow, in contrast to these results was the median
      percentage of CD19+/CD5+ cell, which was higher in peripheral blood (70.4%) than
      in bone marrow (60.9%). The results of this study indicate that CD43 is present
      on peripheral blood B-CLL cells. Moreover, percentage of these cell increases
      during progression of disease however more weakly than percentage of CD5 and CD6
      positive cells. Expression of CD43 is independent from expression CD5 and CD6 and
      diminishes during tumor mass increasing, what can depended from releases
      exocellular domains of CD43. CD43+ cell from B-CLL patients have a tendency to
      accumulation in tissues what is illustrated by higher percentage of CD43+ cell in
      bone marrow than in peripheral blood.

PMID- 10949883
TI  - [Response of vasoactive substance to blood pressure changes during hemodialysis
      in uremic patients].
AB  - Ultrafiltration during haemodialysis (HD) may be the cause of blood pressure (BP)
      decline due to reduction of blood volume. In some patients, however, BP does not
      decrease or even rises during HD. The aim of the study was to answer the
      question: do uraemic hypertensive patients, showing a decline of mean blood
      pressure (MAP) during HD session (group A) differ from those showing a stable MAP
      during HD session (group B) with respect to hormonal profile of aldosterone
      (ALD), vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin-1,2 (ET
      1,2), blood nitric oxide (NO) and plasma renin activity (PRA). A total of 39
      haemodialysed, hypertensive patients (17 female, 22 men) were studied. 24
      patients (group A) showed a MAP decline of 10 mm Hg or more, while 15 patients
      (group B) showed MAP changes of less than +/- 10 mm Hg during HD session. PRA,
      ALD, AVP, ANP, ET-1,2, NO concentration were assessed in blood samples withdrawn
      from the arterial blood line before HD and after 60, 120, 180 and 240 minutes of
      HD session. Plasma ET-1,2 and blood NO concentration were also assessed after 30
      minutes of HD. BV was continuously monitored with a Crit-Line equipment, BP was
      measured before and every 30 minutes on HD. Before HD session both examined
      groups showed similar baseline plasma levels of ALD, AVP, ANP, ET-1,2, NO, PRA
      and MAP. A 4-hours HD induced a significant increase in plasma ALD and AVP
      concentrations and a significant decline in ANP level in both groups of patients.
      In group A, PRA and blood NO concentration increased significantly, while plasma
      ET-1,2, level did not change during HD. In group B, no significant changes in PRA
      and blood NO level were noticed, while plasma ET-1,2 rose markedly. In addition
      in group B, a significant positive correlation was found between MAP and plasma
      ET-1,2 level changes, but a significant negative correlation between MAP and
      blood NO level changes. CONCLUSION: Patients with a decline of MAP over 10 mm Hg
      during HD differ from those with a stable MAP by a different response of plasma
      ET and blood NO to HD induced volume changes.

PMID- 10949884
TI  - [Assessment of plasma fibronectin concentration in type 1 diabetic patients].
AB  - Fibronectin is a family of glycoproteins that are present on many cell surfaces,
      in extracellular matrix and in plasma. Fibronectin might play an important role
      in pathogenesis of chronic diabetic complications. The aim of this study was to
      estimate plasma concentration of fibronectin in patients with recently onset and
      with long duration of type 1 diabetes mellitus. Moreover, the correlation between
      fibronectin concentration and HbA1c, duration of diabetes and late diabetic
      complications was assessed. The study was performed in 18 patients with recently
      onset of diabetes (aged 23.8 +/- 5.3 years, HbA1c 10.63 +/- 0.83%) (group A) and
      21 patients with long history of diabetes (aged 33.9 +/- 10.5 years, mean
      diabetes duration 9.8 +/- 5.8 years, HbA1c 9.24 +/- 2.48%) (group B). The plasma
      concentration of fibronectin was estimated with the use of the ELISA test. The
      plasma fibronectin concentration was significantly higher in type 1 diabetic
      patients in comparison with healthy subjects (381.00 +/- 27.42 and 297.50 +/-
      25.32 micrograms/ml, respectively, p < 0.05). The values observed in the patients
      with recently onset and long duration of diabetes and in the subjects with and
      without diabetic complications did not differ significantly (p > 0.05, p > 0.05).
      We noticed positive correlation between fibronectin concentration and HbA1c (r =
      0.35; p < 0.05) and negative correlation with patients age (r = -0.35; p < 0.05).
      The results of our study suggest, that plasma fibronectin concentration in
      diabetes is increased independently from microangiopathy but rather results from
      hyperglycaemia.

PMID- 10949885
TI  - [Balloon angioplasty of branches of the aortic arch].
AB  - Balloon angioplasty has become a first-line therapy of symptomatic
      brachiocephalic occlusive disease. We review our own results of treatment of
      these lesions for the last two years. 16 patients (18 vessels--6 occlusions) with
      chronic limb ischaemia (9 cases), vertebrobasilar insufficiency (4 cases),
      ischemic stroke (2 cases); in one case angioplasty was performed as prevention
      before major abdominal surgery. Femoral approach was predominantly used; in 3
      occlusions brachial approach was chosen. Stents were implanted in 4 cases of poor
      angioplasty result with severe limb ischaemia. Lesions were crossed in all
      stenoses and in 4 of 6 occlusions. Residual stenosis < 30% was attained in 10
      pts. In 11 cases transstenotic gradient was relieved and a normal flow in
      vertebral artery was reestablished. There were two cases of acute upper limb
      ischaemia, one needed surgery. Reversible ulnar nerve paresis was noted in one
      patient, transient symptoms of postreperfusion syndrome in two. At follow up
      (mean 12 mo, range 1-30 mo) 1 restenosis was recorded. Balloon angioplasty is
      easy, safe and effective for treating brachio-cephalic stenoses. Recanalisation
      of occlusions is more difficult and risky. Treatment of stenoses should not be
      undully postponed; recanalisation should be reserved for patients with more
      advanced symptoms of the disease.

PMID- 10949886
TI  - [Pharmacotherapy of arterial hypertension and pharmacoeconomic aspects of
      hypotensive therapy in elderly patients in Poland].
AB  - The aim of our study was to examine the use of pharmacological therapy and to
      evaluate the economical aspects of treating hypertension (HT) in elderly patients
      in Poland. Two hundred and sixty eight elderly persons (147 females, 121 males;
      mean age: 72.2 +/- 6.0 years) were selected from Polish population by stratified
      and cluster random sampling with quotas. BP measurement was performed 3 times
      every 2 minutes at respondents home. In the questionnaire, awareness of HT was
      assessed. Prevalence of hypertension among subjects aged 65 years and over by JNC
      VI criteria (SAP > or = 140 mm Hg, DAP > or = 90 mm Hg or hypotensive therapy)
      was 74%. Awareness of HT was equal to 61%. Eleven percent of all hypertensives
      were well controlled. Among hypertensives, 71% took prescribed antihypertensive
      drugs on a regular basis. Patients with HT were taking the following
      antihypertensive drugs: diuretics 16%, diuretics and reserpine 20%, beta-blockers
      19%, ACE inhibitors 53%, calcium antagonists 30%, and other 3%. Newer drugs were
      prescribed in 7%, and multi-source (generic) products in 93%. The average cost of
      treatment with one drug was 147 PLN (37.5 USD) per year (newer drugs: 413 PLN;
      multi-source product 126 PLN). Assuming those data and number of elderly people
      in Poland (4.335 mln), we estimated that 3.208 mln of subjects have had
      hypertension according to JNC VI criteria. Only 1.957 mln of patients with HT
      have been detected and only 0.353 mln of hypertensives have been well controlled.
      The approximate global cost of antihypertensive drugs per year in elderly
      patients in Poland has been equal to 285 mln PLN (72.8 mln USD). In hypothetical
      situation with optimal (100%) detection and control of HT the global cost by the
      actual rate of regularity in taking drugs would increase to 569 mln PLN (145.3
      mln USD). The prevalence of HT in elderly people in Poland is very high. In
      elderly hypertensives ACE inhibitors are used most often. More than 90% of
      prescribed drugs are multi-source products. An optimal improvement of HT
      detection and control would cause a two-fold augmentation of the costs of
      pharmacological therapy.

PMID- 10949887
TI  - [Ventricular fibrillation as a symptom of prosthetic valve dysfunction that was
      caused by thrombosis on mitral valve. Surgery or thrombolytic treatment?].
AB  - We discuss the case of 49 years old woman with recurrent thrombosis of prosthetic
      mitral valve with ventricular fibrillation as the complication. For the first
      time thrombotic prosthetic valve Carbo Medics 33 had been removed and the new
      valve--Medtronic Hall 31 mm was implanted in the mitral position. After diagnosis
      of the repeated thrombosis on the replaced prosthetic valve, the patient refused
      the subsequent operation. The fully effective thrombolytic therapy was then
      performed. The patient was discharged from the Department and was asymptomatic 4
      month follow-up.

PMID- 10949888
TI  - [Chondrocalcinosis: rarely diagnosed frequent disease. A case report].
AB  - In this paper we described a case of 56 old patient with history of joint
      disease. We diagnosed chondrocalcinosis with hypomagnesemia. The patient was
      treated for gout during last 13 years. The frequency of chondrocalcinosis is
      estimated about 10% in patients after 50 years of age, but it is very rare
      diagnosed. A correct diagnosis is possible on the basis of simple tests and it
      allows to avoid the drugs which are not effective in this disease.

PMID- 10949889
TI  - [Gastroesophageal reflux disease is an important factor in differential diagnosis
      of chest pain].

PMID- 10949890
TI  - [Right ventricular infarction: pathophysiology, clinical picture. Prognosis].

PMID- 10949891
TI  - [Is Chlamydia pneumoniae infection the risk factor of unstable angina pectoris?].

PMID- 10949892
TI  - [Professor Giorgio Soardo awarded with the Medal of the Polish Society of
      Internal Medicine].

PMID- 10949893
TI  - [The Fourth Middle European Congress of Internal Medicine, Vienna, July 1-3,
      1999].

PMID- 10949894
TI  - [Meeting of the Executive Board of the Central European Congress of Internal
      Medicine, Bratislava, September 6, 1999].

PMID- 10949895
TI  - Predictors related to the occurrence of a measles epidemic in the city of Sao
      Paulo in 1997.
AB  - A matched case-control study was performed to identify risk factors for measles
      during an epidemic that occurred in 1997 in the city of Sao Paulo, in the
      Brazilian state of the same name. Measles cases from the city of Sao Paulo from 1
      January 1997 to 15 August 1997 were included in the study. The criteria for case
      definition were age below 30 years, having received no measles vaccine 5-21 days
      before the onset of rash, and laboratory confirmation by IgM antibodies
      detection. From a bank of confirmed measles cases, 130 cases for each of five age
      ranges (under 1 year, 1-5 years, 6-20 years, 21-24 years, and 25-29 years) were
      picked at random according to a systematic criterion proportional to the number
      of cases in seven areas of the city. Data were collected through a home survey,
      and for each measles case studied two controls matched by age and place of
      residence were selected. The matched conditional logistic regression analysis for
      the potential risk factors from the univariate analysis showed that the best
      predictors for acquiring measles during the epidemic were: lack of measles
      vaccination, previous contact with a measles-like disease at home or on the job,
      having been born either outside the state of Sao Paulo or in a rural area, being
      employed, and spending time in a semiclosed institution, such as a nursery, day
      care center, or school. The risk factors were not homogeneous for the different
      age groups. The data in the present survey suggest that, in addition to lack of
      vaccination, other risk factors should be considered when planning a measles
      vaccination strategy for a developing country.

PMID- 10949896
TI  - [Therapeutic efficacy of different antimalarial regimens in the Costa Rica
      Nicaragua border region].
AB  - The search for short treatments for malaria is still a goal for many developing
      countries. The World Health Organization has recommended a three-day treatment
      with primaquine and quinine, but this treatment is difficult to apply in many
      rural areas because it requires a malaria technician to stay at least three days
      in a community. This is very hard when these communities are dispersed and
      increases the cost of treatment and supplies. This study tested treatments of 1,
      5, and 9 days against a treatment of 14 days. Using the Kaplan-Meier method, no
      statistical difference was found among these four treatment approaches. We
      strongly recommend using the one-day treatment, in and endemic rural areas where
      the population is dispersed and has difficulty accessing health care.

PMID- 10949897
TI  - [Autoantibody profile among Kaingang and Guarani tribe Indians in Southern
      Brazil].
AB  - This study investigated the autoantibody profile of 241 blood samples from 176
      Kaingang and 65 Guarani Indians from three populations living on the Rio das
      Cobras and Ivai reservations, in the state of Parana, in southern Brazil. The
      presence of antimitochondrial, anti-smooth muscle, antinuclear, anti-parietal
      cell, and anti-liver-kidney microsome antibodies was determined by indirect
      immunofluorescence. These results were compared with samples from 100 healthy
      Caucasian individuals from the general population of the state. Total positivity
      was 9% for the indigenous population and 4% for the control population. The
      prevalence of anti-smooth muscle antibodies was significantly higher among the
      Guarani and Kaingang individuals from the Rio das Cobras reservation (P = 0.03).
      It is likely that the increased exposure that these indigenous Brazilians have to
      infectious diseases that were previously unknown to them comes from more contact
      with non-native populations, growing acculturation, and cultural practices that
      include scarification and tattooing. The presence of auto-antibodies in these
      Brazilian Indians may be related to mechanisms of molecular mimicry with viral or
      bacterial antigens.

PMID- 10949898
TI  - The shape of the HIV/AIDS epidemic in Puerto Rico.
AB  - This study presents information on AIDS patients in Puerto Rico, including their
      general sociodemographic profile, some risk-related parameters, characteristics
      of vulnerable groups, and elements of the clinical spectrum of the disease. Data
      were analyzed from the Puerto Rico AIDS Surveillance Program and available
      studies about the HIV/AIDS epidemic in Puerto Rico. A total of 23,089 AIDS cases
      was reported to the Puerto Rico AIDS Surveillance Program from January 1981
      through February 1999. The HIV/AIDS epidemic has affected mostly males and
      females between the ages of 30 and 49, though cases have also been reported for
      other age groups. The cumulative proportion of persons with AIDS who are women
      has increased tremendously, from 11.4% for the 1981-1986 period to 21.6% for the
      entire 1981-1999 period. In Puerto Rico the category of injecting drug users
      (IDUs) accounts for the majority of the AIDS cases (52%), followed by
      heterosexual contact (22%), and men who have sex with men (17%). The three main
      diagnoses for AIDS on the island are wasting syndrome (30.7%); esophageal,
      bronchial, and lung candidiasis (29.4%); and Pneumocystis carinii pneumonia
      (26.8%). According to 1994 vital statistics for Puerto Rico, AIDS was the fourth
      leading cause of death. The overall reported AIDS mortality rate was 42.0 per
      100,000 persons, with the rate for males, 67.8, much higher than it was for
      females, 17.4. AIDS is the first cause of death among persons between 30 and 39
      years old. Intense efforts are needed to better understand the epidemic in Puerto
      Rico and its biology, social and family impacts, and financial costs.

PMID- 10949899
TI  - Performance of yeast-baited traps with Triatoma sordida, Triatoma brasiliensis,
      Triatoma pseudomaculata, and Panstrongylus megistus in laboratory assays.
AB  - The effectiveness of a trap for triatomines baited with yeast cultures has been
      previously demonstrated for Triatoma infestans in laboratory assays. We report
      here results from laboratory assays testing yeast traps for Triatoma sordida,
      Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus megistus. All
      assays were conducted in an open experimental arena 100 cm x 100 cm, with two
      traps placed at opposite sides of the arena. One of the traps contained a yeast
      culture, and the other trap contained a saccharose solution as a control. Two
      series of experiments were done, one without a refuge for the insects and one
      with a refuge. The results obtained clearly demonstrated that the yeast-baited
      traps were effective in the laboratory in capturing both T. sordida and P.
      megistus. For T. sordida, yeast-baited traps captured significantly more bugs
      than did the control traps (t test P value = 0.03). For P. megistus, when a
      refuge was provided during the assay, yeast-baited traps also captured
      significantly more bugs than did the control traps (t test P value = 0.006). In
      the experiments with T. brasiliensis and T. pseudomaculata, both traps captured
      some insects, but the yeast traps captured many fewer bugs than was true with the
      T. sordida and P. megistus bugs. These results indicate that, in the laboratory,
      yeast traps can capture considerable numbers of T. sordida and P. megistus in one
      night. We discuss the potential use of yeast traps for detecting and capturing
      both triatomine species.

PMID- 10949900
TI  - [Detection of Mycobacterium tuberculosis by polymerase chain reaction in a
      selected population in northwestern Mexico].
AB  - This study compares the detection of Mycobacterium tuberculosis through
      bacilloscopy (Ziehl-Neelsen stain), growth in Lowenstein-Jensen medium, and
      polymerase chain reaction (PCR) carried out with DNA taken directly from various
      types of samples. A total of 252 samples were analyzed (114 sputum, 96 urine, 15
      cerebrospinal fluid, and 27 of other types) from 160 patients with any form of
      suspected tuberculosis who came to the Clinical Pathology Laboratory of the
      Specialties Hospital of the Western National Medical Center of the Mexican Social
      Security Institute. In all cases Ziehl-Neelsen stains were done, as were also
      cultures with Lowenstein-Jensen medium and PCR amplification of a segment of 285
      base pairs specific to the M. tuberculosis complex. Of the 252 samples, with the
      culture, 18 were positive for nontuberculous mycobacteria. Of the 234 others, 12
      (5.1%) were positive with the PCR and the culture, 174 (74.4%) negative in both
      tests, 47 (20.1%) positive with the PCR and negative with the culture, and 1
      (0.4%) negative with the PCR and positive with the culture. Using the culture as
      the reference test, the PCR provided a sensitivity of 92.3%, a specificity of
      78.7%, a positive predictive value of 20.3%, and a negative predictive value of
      99.4%. The PCR detection limit with DNA taken from culture was 10 fg, equivalent
      to four or five mycobacteria. Also in comparison with the culture, the PCR
      correctly identified the totality of the mycobacteria of the M. tuberculosis
      complex. Taking the culture as the reference test, when analyzing just the sputum
      samples, the direct PCR provided a sensitivity of 90.9%, a specificity of 89.5%,
      a positive predictive value of 52.6%, and a negative predictive value of 98.7%.
      The PCR is a sensitive and specific technique for detecting the M. tuberculosis
      complex in both positive and negative bacilloscopy samples. A controlled PCR
      procedure makes it possible to establish or to exclude the diagnosis of
      tuberculosis in a time that is reduced from more than three weeks to just 24 to
      48 hours. This is particularly useful when an early diagnosis is needed to
      establish a patient's prognosis or in organ transplant cases.

PMID- 10949901
TI  - [Anatomy practice and medical education].
AB  - Medical education is committed to a distant and impersonal model of medical care
      that does not take into consideration the complexity of the encounter between
      physician and patient. Some authors believe that the "dehumanizing posture" of
      physicians is encouraged by the pedagogical practice of dissecting cadavers. In
      this sense the relationship between student and cadaver would be a model
      preceding and shaping the relationship between physician and patient. This
      article describes a study on the impact of anatomy practice on first-semester
      medical students enrolled in the anatomy course at the Federal University of Rio
      de Janeiro, Brazil. Groups of 16 students attended four 1-hour meetings over the
      semester. Thirty-two groups were assessed over four semesters, with a total of
      384 students. The activity was coordinated by medical psychology and anatomy
      professors, who took notes during the sessions. At the end of each semester the
      students filled out a questionnaire to help evaluate this teaching activity. In
      the groups, the most frequent themes were the first encounter with the cadaver,
      respect for the cadaver, and the presence or absence of humanity in the cadaver.
      In general the questionnaire showed that the students found the experience to be
      positive. We believe that the pedagogical activity described here provides an
      opportunity to reverse the gloomy state of affairs of dehumanized medical care.
      Group discussions help decrease students' anxiety with the cadaver. This in turn
      results in a more humane model for the physician-patient relationship and
      promotes change in the ideology of coldness and distance on the part of the
      physician. The paradox of medical education--being technical and also having to
      take into account the complexity of human relationships--can be resolved through
      activities such as this one.

PMID- 10949902
TI  - Hospital accreditation in Latin America.

PMID- 10949903
TI  - [Fatigue and practice effects during cognitive tasks lasting several hours].
AB  - In psychometric studies of cognitive performance that last several hours there
      are two major potential influences on performance. Fatigue and loss of motivation
      may lead to a drop in performance while effects of practice on similar tasks can
      possibly help to improve results. Besides the effects on mean scores there is
      also the possibility of a change in the reliability or in the relations between
      single tasks and the constructs intended to be measured, thus an effect on
      validity. In two studies with subjects working on intelligence and working memory
      tasks for a total of 9 hours distributed over 2 days in each study we tried to
      capture and separate effects of practice and fatigue using a quasi-experimental
      manipulation. In both studies (N = 128 and N = 133) the participants worked on
      the Berlin Structure of Intelligence Test (BIS-test) and on batteries of
      computerized working memory tasks. Groups of subjects were assigned to
      experimental conditions in which they worked on two parallel versions of a
      working memory task at the beginning and the end of one session in the order A/B
      (condition one), B/A (condition two) or on both versions at the end (condition
      three). In one of the studies subjects also completed a fatigue questionnaire at
      the beginning and the end of the session and two personality scales. Results show
      that there are weak effects of practice but only a trivial loss of performance
      due to the cognitive strain of several hours. Changes of reliabilities and of
      correlations with criteria are not significant.

PMID- 10949904
TI  - [Flexibility of mental representations of spatial information as a function of
      perspective during learning].
AB  - View-based theories of the mental representation of spatial information claim
      that distinct views experienced during learning are represented separately in
      memory. Networks of such views are considered to be the basis for spatial
      navigation. Two experiments (N = 56) investigated the role of observer
      perspective on the resulting mental representation when learning a spatial
      configuration on the computer. Learning in route perspective, which induced the
      impression of passive navigation through the configuration, was compared with a
      survey perspective, which consisted of an overview of the whole configuration
      from one point of view. In accordance with view-based theories, previously seen
      views could be identified faster and with less error than new views for both
      perspectives during learning. Recoding the information into the alternative
      perspective was also possible. If participants were asked to integrate distinct
      route views into a survey view during learning, the flexibility of the resulting
      mental representation was greatly increased. This indicates that conscious
      processes such as imagery play an important role in the integration of spatial
      knowledge.

PMID- 10949905
TI  - [Decomposition studies on the core function of working memory].
AB  - By means of decomposition we investigated using an experimental design (n = 160)
      the impact of combinations of processing and retention requirements on
      performance. Retention-during-processing spans (i.e., dual task requirements with
      equal importance of both evaluated components) were compared with the "reading"
      (final word) span of read sentences. In a correlational design, the relationships
      of these intentional spans and a unintentional indicator of working memory (the
      pronoun inference distance) were compared with fluid intellectual performances.
      The effects of processing on the span may not be restricted to articulatory
      suppression of rehearsal. While the substitution of retention of an additional
      processing-independent item improved the span, this did not hold for items
      resulting from processing. Thus, the span is determined by coordination of
      retention with processing, but neither by an activity without retention nor by
      retention per se. Coordination requires resources in addition to those required
      by the activities to be coordinated. Strategies of coordination differing in
      their efficiency result in different spans. Both unintentional processes and
      intentional ones contribute to the dual task performance of the retention-during
      processing type. The best predictors for fluid verbal and nonverbal intellectual
      performance are the unintentional (pronoun) inferences and the complex
      intentional retention-during-processing span. The results are in favor of a
      working memory model in terms of a set of functions.

PMID- 10949906
TI  - [How does model- and situation-specific lack of knowledge affect causal
      inferences?].
AB  - A model proposed by Thuring (1991) for inferences based on causal knowledge was
      empirically tested. According to this model, two variables affect the certainty
      with which a causal inference is concluded: insufficiency (model-specific
      uncertainty) and ambiguity (situation-specific uncertainty). Within an experiment
      these two variables were manipulated. Both had a very significant (p < .01)
      influence on causal inferences. In respect to its quantity, variation of
      ambiguity had the effect predicted in the model. Concerning insufficiency,
      distinct differences between predicted and empirical ratings were found. Reasons
      for these deviations and model modifications resulting therefrom are discussed.

PMID- 10949907
TI  - Insulin-like growth factor I and urokinase-type plasminogen activator
      bioregulation system as a survival mechanism of prostate cancer cells in
      osteoblastic metastases: development of anti-survival factor therapy for hormone
      refractory prostate cancer.

PMID- 10949908
TI  - Myocardial postischemic injury is reduced by polyADPripose polymerase-1 gene
      disruption.
AB  - BACKGROUND: PolyADPribose polymerase (PARP) is activated by DNA strand breaks to
      catalyze the addition of ADPribose groups to nuclear proteins, especially PARP-1.
      Excessive polyADPribosylation leads to cell death through depletion of NAD+ and
      ATP. MATERIALS AND METHODS: In vivo PARP activation in heart tissue slices was
      assayed through conversion of [33P]NAD+ into polyADPribose (PAR) following
      ischemia-reperfusion (I/R) and also monitored by immunohistochemical staining for
      PAR. Cardiac contractility, nitric oxide (NO), reactive oxygen species (ROS),
      NAD+ and ATP levels were examined in wild type (WT) and in PARP-1 gene-deleted
      (PARP-1(-/-)) isolated, perfused mouse hearts. Myocardial infarct size was
      assessed following coronary artery occlusion in rats treated with PARP
      inhibitors. RESULTS: Ischemia-reperfusion (I/R) augmented formation of nitric
      oxide, oxygen free radicals and PARP activity. I/R induced decreases in cardiac
      contractility and NAD+ levels were attenuated in PARP-1(-/-) mouse hearts. PARP
      inhibitors reduced myocardial infarct size in rats. Residual polyADPribosylation
      in PARP-1(-/-) hearts may reflect alternative forms of PARP. CONCLUSIONS:
      PolyADPribosylation from PARP-1 and other sources of enzymatic PAR synthesis is
      associated with cardiac damage following myocardial ischemia. PARP inhibitors may
      have therapeutic utility in myocardial disease.

PMID- 10949909
TI  - Induction of neonatal tolerance to oxidized lipoprotein reduces atherosclerosis
      in ApoE knockout mice.
AB  - BACKGROUND: In the course of atherosclerosis, humans and apolipoprotein (apoE)
      Knockout (KO) mice exhibit an active cell-mediated and humoral immune process,
      both at the systemic level and within atheromata. Low density lipoproteins (LDL)
      infiltrate the vascular wall, where they are oxidatively modified. This oxidative
      modification may generate new epitopes for which tolerance is not achieved during
      ontogenesis. Such epitopes could constitute new targets for autoreactive immune
      responses that may have a physiopathological role in disease development.
      MATERIALS AND METHODS: Exposing mice to high dose of antigens during thymic T
      cell education induces immunological tolerance to the administered antigens. We
      injected newborn apoE KO mice with oxidized LDL. They were fed a cholesterol-rich
      diet and aortic atherosclerosis, cell-mediated immune response, and T-cell
      repertoire were analyzed after 5 months. RESULTS: Injection of oxidized LDL at
      birth reduced not only the immune response to oxidized LDL, but also
      susceptibility to atherosclerosis in apoE mice. Injection of oxidized LDL induced
      T-cell tolerance due to clonal deletion, rather than anergy of the reactive T
      cells. The T-cell repertoire of apoE KO mice was affected by the development of
      the disease, whereas tolerization normalized it. CONCLUSIONS: This study
      demonstrates that the immune response against oxidized LDL has a deleterious role
      in atherogenesis and that a fine-tuning of this response could modify the course
      of the disease.

PMID- 10949910
TI  - Quantification of Alzheimer amyloid beta peptides ending at residues 40 and 42 by
      novel ELISA systems.
AB  - BACKGROUND: The amyloid beta (Abeta) peptide is a key molecule in the
      pathogenesis of Alzheimer's disease. Reliable methods to detect and quantify
      soluble forms of this peptide in human biological fluids and in model systems,
      such as cell cultures and transgenic animals, are of great importance for further
      understanding the disease mechanisms. In this study, the application of new and
      highly specific ELISA systems for quantification of Abeta40 and Abeta42 (Abeta
      peptides ending at residues 40 or 42, respectively) in human cerebrospinal fluid
      (CSF) are presented. MATERIALS AND METHODS: Monoclonal antibodies WO-2, G2-10 and
      G2-11 were thoroughly characterized by (SPOT) epitope mapping and
      immunoprecipitation/mass spectrometry. We determined whether aggregation affected
      the binding capacities of the antibodies to synthetic peptides and whether
      components of the CSF affected the ability of the antibodies to bind synthetic
      Abeta1-40 and Abeta1-42 peptides. The stability of Abeta40 and Abeta42 in CSF
      during different temperature conditions was also studied to optimize sample
      handling from lumbar puncture to Abeta assay. RESULTS: The detection range for
      the ELISAs were 20-250 pM. The intra-assay variations were 2% and 3%, and the
      inter-assay variations were 2% and 10% for Abeta40 and Abeta42, respectively. The
      antibodies specifically detected the expected peptides with equal affinity for
      soluble and fibrillar forms of the peptide. The presence of CSF obstructed the
      recognition of synthetic peptides by the antibodies and the immunoreactivity of
      endogenous CSF Abeta decreased with increasing storage time and temperature.
      CONCLUSIONS: This study describes highly sensitive ELISAs with thoroughly
      characterized antibodies for quantification of Abeta40 and Abeta42, an important
      tool for the understanding of the pathogenesis of Alzheimer's disease. Our
      results pinpoint some of the difficulties associated with Abeta quantification
      and emphasize the importance of using a well-documented assay.

PMID- 10949911
TI  - PLC-gamma1 signaling pathway and villin activation are involved in actin
      cytoskeleton reorganization induced by Na+/Pi cotransport up-regulation.
AB  - BACKGROUND: The brief incubation of opossum kidney (OK) cells with low P(i)
      results in Na+/P(i) cotransport up-regulation and in substantial, but transient,
      cytoskeletal reorganization. In this study, we examined signaling events involved
      in the depolymerization of microfilaments. RESULTS: Confocal laser scanning
      microscopy, immunoblot and immunoprecipitation experiments revealed villin co
      localization with mainly actin short filaments and monomers, indicating that
      under the conditions used, villin acted as an actin-severing protein. Further
      analysis revealed that low concentrations of extracellular phosphate resulted in
      phospholipase Cgammal (PLC-gammal) translocation to the actin cytoskeleton,
      without increases in its tyrosine phosphorylation. Additionally, tyrosine
      phosphorylation of a portion of insoluble villin was increased; whereas, only
      tyrosine phosphorylated villin associated with PLC-gammal. Although, tyrosine
      phosphorylation of PLC-gammal was not observed during Na+/P(i) cotransport up
      regulation, genistein treatment abolished the enzyme's translocation to the actin
      cytoskeleton, as well as its association with villin. In addition, villin was
      found to associate with the 85-KDa subunit (p85) of phosphatidylinositol (PI)-3
      kinase, concomitant with PLC-gammal, in the cytoskeletal fraction of Na+/P(i)
      cotransport up-regulated cells. CONCLUSIONS: Our observations suggest a signaling
      mechanism linking low ambient P(i) levels to the acute up-regulation of its
      cotransport with sodium and the depolymerization of the subcortical actin
      cytoskeleton.

PMID- 10949912
TI  - Exclusion of angiotensin I-converting enzyme as a candidate gene involved in
      exudative inflammatory resistance in F344/N rats.
AB  - BACKGROUND: Inbred LEW/N and F344/N rats respectively, are susceptible and
      relatively resistant to a broad range of inflammatory/autoimmune diseases. We
      recently identified a quantitative trait locus (QTL) on chromosome 10 that
      protects the F344/N rat from carrageenan-induced exudation in a dominant fashion.
      Angiotensin I-converting enzyme (ACE) is one of the candidate genes located in
      this QTL region that plays an important role in inflammation. MATERIALS AND
      METHODS: RNA was extracted from both LEW/N and F344/N rat strains and used to
      produce full length cDNA by reverse transcription polymerase chain reaction (RT
      PCR). Both strands of the PCR products were entirely sequenced to determine
      nucleotide differences between strains. ACE activity was measured using the
      synthetic substrate 3H-hippuryl-glycylglycine. ACE protein levels were determined
      by Western blot using a specific ACE antibody. ACE kinetic and inhibition studies
      were performed using specific substrates (Hip-His-Leu and Acetyl-Seryl-Aspartyl
      Acetyl-Lysyl-Proline) and inhibitors (lisinopril, captopril and quinaprilat) for
      each C- and N-terminal active site. Finally, the dose-effects of lisinopril
      treatment on carrageenen-induced exudate volume and ACE activity was studied.
      RESULTS: In this study, we report for the first time a missense mutation in the
      coding region of ACE cDNA at 5' 1021 from C to T, resulting in a Leu-341 to Phe
      substitution, close to the N-domain active site in the F344/N rats. Full
      characterization of soluble and tissue ACE in both LEW/N and F344/N rat strains
      showed that soluble ACE levels in serum and exudate were 1.5 fold higher in the
      F344/N rats than those in LEW/N rats. In addition, the soluble ACE level was
      inversely correlated with the exudate volume. However, the specific ACE activity
      and its catalytic properties were identical in both strains. Furthermore, the
      chronic inhibition of serum and exudate ACE levels by lisinopril treatment did
      not affect the exudate volume in F344/N rats, indicating that several factors
      besides ACE were involved in the control of carrageenan-induced exudation.
      CONCLUSIONS: This report describes a complete molecular, biochemical, enzymatic
      and pharmacologic study of a missense mutation in the ACE cDNA in F344/N rats,
      that taken together, excludes ACE as a candidate gene involved with resistance to
      carrageenan-induced exudation in F344/N rats.

PMID- 10949913
TI  - Transfer factors: identification of conserved sequences in transfer factor
      molecules.
AB  - BACKGROUND: Transfer factors are small proteins that "transfer" the ability to
      express cell-mediated immunity from immune donors to non-immune recipients. We
      developed a process for purifying specific transfer factors to apparent
      homogeneity. This allowed us to separate individual transfer factors from
      mixtures containing several transfer factors and to demonstrate the antigen
      specificity of transfer factors. Transfer factors have been shown to be an
      effective means for correction of deficient cellular immunity in patients with
      opportunistic infections, such as candidiasis or recurrent Herpes simplex and to
      provide prophylactic immunity against varicella-zoster in patients with acute
      leukemia. MATERIALS AND METHODS: Transfer factors of bovine and murine origin
      were purified by affinity chromatography and high performance liquid
      chromatography. Cyanogen bromide digests were sequenced. The properties of an
      apparently conserved sequence on expression of delayed-type hypersensitivity by
      transfer factor recipients were assessed. RESULTS: A novel amino acid sequence,
      LLYAQDL/VEDN, was identified in each of seven transfer factor preparations. These
      peptides would not transfer expression of delayed-type hypersensitivity to
      recipients, which indicates that they are not sufficient for expression of the
      specificity or immunological properties of native transfer factors. However,
      administration of the peptides to recipients of native transfer factors blocked
      expression of delayed-type hypersensitivity by the recipients. The peptides were
      not immunosuppressive. CONCLUSIONS: These findings suggest that the peptides may
      represent the portion of transfer factors that binds to the "target cells" for
      transfer factors. Identification of these cells will be helpful in defining the
      mechanisms of action of transfer factors.

PMID- 10949914
TI  - Interaction between the actions of taurine and angiotensin II.
AB  - The amino acid, taurine, is an important nutrient found in very high
      concentration in excitable tissue. Cellular depletion of taurine has been linked
      to developmental defects, retinal damage, immunodeficiency, impaired cellular
      growth and the development of a cardiomyopathy. These findings have encouraged
      the use of taurine in infant formula, nutritional supplements and energy
      promoting drinks. Nonetheless, the use of taurine as a drug to treat specific
      diseases has been limited. One disease that responds favorably to taurine therapy
      is congestive heart failure. In this review, we discuss three mechanisms that
      might underlie the beneficial effect of taurine in heart failure. First, taurine
      promotes natriuresis and diuresis, presumably through its osmoregulatory activity
      in the kidney, its modulation of atrial natriuretic factor secretion and its
      putative regulation of vasopressin release. However, it remains to be determined
      whether taurine treatment promotes salt and water excretion in humans with heart
      failure. Second, taurine mediates a modest positive inotropic effect by
      regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine
      has not been examined in human tissue, it is significant that it bypasses the
      major calcium transport defects found in the failing human heart. Third, taurine
      attenuates the actions of angiotensin II on Ca2+ transport, protein synthesis and
      angiotensin II signaling. Through this mechanism taurine would be expected to
      minimize many of the adverse actions of angiotensin II, including the induction
      of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE
      inhibitors are the mainstay in the treatment of congestive heart failure, this
      action of taurine is probably very important.

PMID- 10949915
TI  - Polyamines and thiols in the cytoprotective effect of L-cysteine and L-methionine
      on carbon tetrachloride-induced hepatotoxicity.
AB  - The relationship between cellular glutathione (GSH), protein-SH levels, and
      lactate dehydrogenase (LDH), with respect to the effect of polyamines on the
      cytoprotective ability of L-cysteine and L-methionine, the most important
      components in the sulfur amino acid metabolic pathway, in carbon tetrachloride
      (CCl4)-induced toxicity in isolated rat hepatocytes was studied. CCl4 induced a
      LDH release and decreased cellular thiols and polyamines levels but treatment
      with L-cysteine and L-methionine reversed these decreases. Treating with
      methylglyoxal bis-(guanylhydrazone), MGBG, an irreversible inhibitor of S
      adenosylmethionine decarboxylase, which is a key enzyme in spermidine and
      spermine biosynthesis, and therefore used to deplete cellular polyamines,
      prevented the protective effect of L-cysteine and L-methionine, but the addition
      of exogenous polyamines inhibited the influence of MGBG. These results suggest
      that the cytoprotective effect of L-cysteine and L-methionine in CCl4-induced
      toxicity were via maintenance of cellular polyamines, GSH and protein-SH
      concentrations and prevention of LDH leakage.

PMID- 10949917
TI  - Determination of L- and D-amino acids in foodstuffs by coupling of high
      performance liquid chromatography with enzyme reactors.
AB  - A technique is described for the enantiomeric determination of L- and D-amino
      acids. It works on the principle that the separation efficiency of high
      performance liquid chromatography is coupled with the specificity of enzymes and
      the sensitivity of electrochemical detection. After separation on a lithium
      cation-exchange column the amino acids are converted into keto acids and hydrogen
      peroxide under catalyzation of L- or D-amino acid oxidase. Hydrogen peroxide is
      detected amperometrically. The method has been tested by the analysis of beer,
      port, sherry, wine and fruit juice. A main emphasis was put onto the
      determination of D-alanine which can serve as an indicator for bacterial
      contamination. It is shown that a coupling of HPLC with enzyme reactors is a
      suitable technique for the rapid detection of this marker.

PMID- 10949916
TI  - Insertion of foreign epitopes in HBcAg: how to make the chimeric particle
      assemble.
AB  - Hepatitis B core antigen is one of the most promising protein carriers of foreign
      epitopes of various human and animal pathogens. Chimeric HBcAg particles can be
      used as effective artificial immunogenes. Unfortunately, not all chimeric
      proteins are able to be particulated. The dependence of correct or incorrect
      folding of chimeric proteins on physical and chemical properties of inserts was
      studied with the help of ProAnalyst, SALIX and QSARPro computer programs. We have
      found that insertion of amino acids with high hydrophobicity, large volume, and
      high beta-strand index prevent self-assembling chimeric proteins. These factors
      are most important for the C-termini of inserts. Recommendations for obtaining
      correct folding of chimeric HBcAg particles have been given.

PMID- 10949918
TI  - Effects of testosterone and 17, beta-estradiol on the polyamine metabolism in
      cultivated normal rat kidney epithelial cells.
AB  - Ornithine decarboxylase (ODC) and diamine oxidase (DAO) are important enzymes
      involved in the metabolism of polyamines (putrescine, spermidine and spermine).
      The influence of testosterone (T) and 17, beta-estradiol (E2) on the activity of
      ODC and DAO was examined in cultivated normal rat kidney (NRK) epithelial cells.
      The results showed an increase in enzyme activities 4 hours or 12 hours after
      hormonal treatment. Both T and E2 led to a significant increase (1.6-fold) in ODC
      protein level as compared to the controls. Cellular concentration of spermidine
      and spermine increased (2.2- and 2.6-fold respectively) 4 hours after T addition.
      A higher levels in concentrations of putrescine (1.4-fold) and spermine (1.5
      fold) 12 hours after E2 treatment were observed. These results suggest that the
      biosynthesis and terminal oxidation of the polyamines in NRK epithelial cells are
      androgen- and estrogen-mediated and depend on the hormonal sensitivity of the
      cells.

PMID- 10949919
TI  - Studies of aminochrome toxicity in a mouse derived neuronal cell line: is this
      toxicity mediated via glutamate transmission?
AB  - Aminochrome was found to be toxic in a mouse-derived neuronal cell line (CNh).
      The effect was concentration dependent (10-150microM). The issue whether
      aminochrome toxicity involves glutamate transmission was studied with several
      glutamate receptors antagonists. Incubation of the cells with aminochrome
      (150microM) in the presence of 100microM of the AMPA antagonist, NBQX resulted in
      an increase of cell survival, from 52 to 73%. However, this protective effect did
      not seem to be related to activation of ionotropic glutamate receptors since
      incubation of CNh cells with 200microM of glutamate resulted in only 10% decrease
      of cell survival. However, NBQX was found to inhibit in vitro the autoxidation
      process. One hundred microM AP-5 did not have any effect on aminochrome toxicity.
      The toxic effect of aminochrome on CNh cells seems to be dependent of
      extracellular activation since addition of dicoumarol, a specific inhibitor of DT
      diaphorase, did not affect that toxicity, which can be explained perhaps by a
      lack of a transport system for aminochrome into the CNh cells.

PMID- 10949920
TI  - Isozymic nature of spore coat-associated alanine racemase of Bacillus subtilis.
AB  - Spore coat-associated alanine racemase of Bacillus subtilis, which converts L
      alanine to D-alanine, that is, the germinant to the competitive inhibitor, to
      regulate spore germination for survival of the organism under unfavorable growth
      conditions, was examined. The dormant spores, L-alanine-initiated germination of
      which is inhibited by diphenylamine, were used to characterize the enzyme in the
      native form because of its unextractablility from dormant spores. The presence of
      isozymes, Enz-I and Enz-II with Km for L-alanine of about 20mM and 50mM and
      optimum activity at around 40 degrees C and 65 degrees C, respectively, was
      proposed. The enzymes were selectively used depending on the L-alanine
      concentration and the temperature. The pH profiles of the activity (optimun at pH
      9.0) and the stability (stable between pH 6-11 at 60 degrees C) were similar, but
      Enz-II was more heat-stable than Enz-I and the denaturation curve demonstrated a
      two-domain structure for Enz-II. Sensitivity to D-penicillamine, hydroxylamine
      and HgCl2 was similar between Enz-I and Enz-II, while that to D-cycloserine, L-
      and D-aminoethylphosphonic acid, monoiodoacetate and N-ethylmaleimide was
      different; HgCl2 was the most effective inhibitor among these compounds.

PMID- 10949921
TI  - Taurine and pulmonary hemodynamics in sepsis.
AB  - This study has been performed to characterize the relationship between changes in
      plasma taurine (TAU) and hemodynamic patterns in sepsis. Analysis of 249 plasma
      aminoacidograms (AA-grams) and associated measurements in a group of critically
      ill, mechanically ventilated septic patients, showed that decreases in TAU were
      significantly correlated with increases in pulmonary artery pressure and
      pulmonary vascular resistance, and with worsening of pulmonary dysfunction. All
      cases requiring positive end-expiratory pressure greater than 10cmH2O had TAU
      lower than 50 microM/L. Low TAU was paralleled by decreases in other sulfur
      containing AA, phosphoethanolamine, beta-alanine, glutamate and aspartate, within
      a pattern of greater metabolic dysregulation. These data provide evidence of a
      link between severity of pulmonary dysfunction and reduced TAU availability in
      clinical sepsis. The implications relate also to the need for specific
      investigations of the clinical effect of exogenous TAU on proinflammatory
      mediator-induced pulmonary dysfunction.

PMID- 10949922
TI  - Androgenic sensitivity of polyamine-oxidizing enzyme activities in female rat
      tissues.
AB  - Effects of testosterone (10 micrograms/100g body weight) on polyamine-oxidizing
      enzyme activities in female rat uterus, liver and kidney were demonstrated.
      Testosterone-treated rats exhibited 2.07 fold (p < 0.002) higher uterine
      polyamine oxidase (PAO) activity and 1.93 fold (p < 0.02) higher diamine oxidase
      (DAO) activity, as compared to the controls. In the liver, testosterone caused an
      elevation in PAO (1.39 fold, p < 0.05), but not in DAO activity, whereas in
      kidney the hormone stimulated DAO (1.30 fold, p < 0.05), but not PAO activity.
      The effects observed suggest a possible role for testosterone in the modulation
      of polyamine levels in the female organs studied and especially in uterus.

PMID- 10949923
TI  - Switch from p53 to MDM2 as differentiating human keratinocytes lose their
      proliferative potential and increase in cellular size.
AB  - p53 transcription factor is mutated in most skin cell carcinomas and in more than
      50% of all human malignancies. One of its transcriptional targets is MDM2, which
      in turn down-regulates p53. The role of the p53/MDM2 regulatory loop upon
      genotoxic stress is well documented, but less is known about its role in normal
      tissue homeostasis. We have explored this pathway during the different
      transitions of the human epidermal differentiation programme and after isolating
      stem cells, transit amplifying cells or differentiating cells from epidermis.
      Maximum expression of p53 was found in proliferating keratinocytes. A striking
      and transient induction of MDM2 and a down-modulation of p53 characterized the
      transition from proliferation to differentiation in primary human keratinocytes.
      These changes were delayed in late differentiating carcinoma cells, and were
      clearly different in suspended primary fibroblasts. Interestingly, these changes
      correlated with an increase in cell size, at the time of irreversible commitment
      to differentiation. Induction of MDM2 was also associated with suppression of
      proliferation in normal, or hyperproliferative, psoriatic epidermis. Moreover,
      both proteins were induced as keratinocytes were driven to leave the stem cell
      compartment by c-Myc activation. Overall, our results show a critical regulation
      of the p53/MDM2 pathway at the epidermal transition from proliferation to
      differentiation.

PMID- 10949924
TI  - Mutations in the beta-propeller domain of the Drosophila brain tumor (brat)
      protein induce neoplasm in the larval brain.
AB  - Inactivation of both alleles of the fruit fly D. melanogaster brain tumor (brat)
      gene results in the production of a tumor-like neoplasm in the larval brain, and
      lethality in the larval third instar and pupal stages. We cloned the brat gene
      from a transposon-tagged allele and identified its gene product. brat encodes for
      an 1037 amino acid protein with an N-terminal B-boxl zinc finger followed by a B
      box2 zinc finger, a coiled-coil domain, and a C-terminal beta-propeller domain
      with six blades. All these motifs are known to mediate protein-protein
      interactions. Sequence analysis of four brat alleles revealed that all of them
      are mutated at the beta-propeller domain. The clustering of mutations in this
      domain strongly suggests that it has a crucial role in the normal function of
      Brat, and defines a novel protein motif involved in tumor suppression activity.
      The brat gene is expressed in the embryonic central and peripheral nervous
      systems including the embryonic brain. In third instar larva brat expression was
      detected in the larval central nervous system including the brain and the ventral
      ganglion, in two glands - the ring gland and the salivary gland, and in parts of
      the foregut - the gastric caecae and the proventriculus. A second brat-like gene
      was found in D. melanogaster, and homologs were identified in the nematode,
      mouse, rat, and human. Accumulated data suggests that Brat may regulate
      proliferation and differentiation by secretion/transport-mediated processes.

PMID- 10949925
TI  - Activation of the insulin-like growth factor II transcription by aflatoxin B1
      induced p53 mutant 249 is caused by activation of transcription complexes;
      implications for a gain-of-function during the formation of hepatocellular
      carcinoma.
AB  - Aflatoxin B1 (AFB1) induced mutation of the p53 gene at codon 249 (p53mt249) is
      critical during the formation of hepatocellular carcinoma (HCC) following
      hepatitis B virus (HBV) infection. p53mt249 markedly increases insulin-like
      growth factor II (IGF-II) transcription largely from promoter 4, accumulating the
      fetal form of IGF-II. Modulation of the transcription factor binding to IGF-II P4
      by wild-type p53 and p53mt249 was identified. Wild-type p53 inhibited binding of
      transcription factors Sp1 and TBP on the P4 promoter, while p53mt249 enhanced the
      formation of transcriptional complexes through enhanced DNA-protein (Sp1 or TBP)
      and protein-protein (Sp1 and TBP) interactions. p53mt249 stimulates transcription
      factor Sp1 phosphorylation which might be a cause of increased transcription
      factor binding on the P4 promoter while wild-type p53 does not. Transfection of
      hepatocytes with p53mt249 impaired induction of apoptosis by the HBV-X protein
      and TNF-alpha. Therefore, the blocking of apoptosis through enhanced production
      of IGF-II should provide a favorable opportunity for the selection of transformed
      hepatocytes. These results explain the molecular basis for the genesis of HCC by
      p53mt249 which was found to be induced by a potent mutagen, AFB1.

PMID- 10949926
TI  - Binding of human papillomavirus 16 E5 to the 16 kDa subunit c (proteolipid) of
      the vacuolar H+-ATPase can be dissociated from the E5-mediated epidermal growth
      factor receptor overactivation.
AB  - Human papillomavirus type 16 E5 protein (HPV16 E5) upregulates ligand-mediated
      activation of the epidermal growth factor receptor (EGFR) in transfected human
      keratinocytes. HPV16 E5 binds to the 16 kDa proteolipid (subunit c) of the
      vacuolar H+-ATPase (16K), responsible for endosomal acidification, and this
      binding has been suggested to be responsible for increased recycling of the
      EGFRs. Using mutant deletions we show here that amino acids 54-78, but not 79-83
      are necessary for binding to the 16K proteolipid. EGF treatment of cells
      expressing wild type or mutants of the E5 protein show that deletion of the last
      carboxy terminal 5 amino acids results in loss of E5-mediated EGFR
      overactivation. Thus, our results show that the binding capacity of HPV16 E5 to
      16K can be dissociated from the effect of the viral protein on EGFR activation.

PMID- 10949927
TI  - Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C
      patients.
AB  - To discriminate among the chromosomal abnormalities associated with the etiology
      of hepatocellular carcinoma (HCC), we performed a comparative genomic
      hybridization (CGH) analysis on 34 HCCs resected on non-cirrhotic livers from
      patients serologically negative for both hepatitis B (HBV) and C (HCV) viruses.
      The results were compared to those of a previous analysis of 50 HCCs selected on
      the basis of their positivity for HBV infection. The majority of the
      abnormalities found in the HBV positive cases (losses of chromosome arms 1p, 8p,
      6q, 13q and 14q and gains of 1q, 8q, 6p and 17q) were similarly detected in the
      virus negative specimens. In contrast, a significant decrease (40% on average)
      was observed for losses at 4q, 16q and 17p in non-viral HCC samples, suggesting
      that these abnormalities are tightly associated with HBV infection. Thus, in
      addition to a common pathway towards malignancy, a subset of alterations may
      preferentially contribute to virus-induced carcinogenesis. In a parallel CGH
      study of 10 fibrolamellar carcinomas, a rare subtype of HCC, we found in six out
      of the seven informative cases, gains of chromosome arm 1q. This region, which is
      also preferentially amplified in non fibrolamellar tumors (58%), may contain an
      essential proto-oncogene commonly implicated in liver carcinogenesis.

PMID- 10949928
TI  - Cloning and expression of human B cell-specific transcription factor BACH2 mapped
      to chromosome 6q15.
AB  - The transcription factor Bach2, a member of the BTB-basic region leucine zipper
      (bZip) factor family, binds to a 12-O-tetradecanoylphorbol-13-acetate (TPA)
      responsive element and the related Maf-recognition element (MARE) by forming
      homodimers or heterodimers with Maf-related transcription factors. Bach2
      regulates transcription by binding to these elements. To understand the function
      in hematopoiesis, we isolated a cDNA clone for human Bach2 (BACH2) encoding a
      protein of 841 amino acid residues with a deduced amino acid sequence having
      89.5% identity to mouse homolog. Among human hematopoietic cell lines, BACH2 is
      expressed abundantly only in some B-lymphocytic cell lines. RT-PCR analysis of
      hematopoietic cells revealed that BACH2 mRNA is expressed in primary B-cells.
      Enforced expression of BACH2 in a human Burkitt cell line, RAJI that does not
      express endogenous BACH2, resulted in marked reduction of clonogenic activity,
      indicating that BACH2 possesses an inhibitory effect on cell proliferation. By
      fluorescent in situ hybridization, the BACH2 gene was localized to chromosome
      6q15. Because deletion of the long arm of chromosome 6 (6q) is one of the
      commonest chromosomal alterations in human B-cell lymphoma, we examined for the
      loss of heterozygosity (LOH) of the BACH2 gene in human B-cell non-Hodgkin's
      lymphomas (NHL). Among 25 informative cases, five (20%) showed LOH. These results
      indicate that BACH2 plays important roles in regulation of B cell development.

PMID- 10949929
TI  - Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is
      required for embryoid body differentiation.
AB  - The role of FGF signaling in early epithelial differentiation was investigated in
      ES (embryonic stem) cell derived embryoid bodies. A dominant negative fibroblast
      growth factor receptor (FGFR) mutation was created by stably introducing into ES
      cells an Fgfr2 cDNA, truncated in its enzymatic domains. These cells failed to
      differentiate into cystic embryoid bodies. No epithelial differentiation and
      cavitation morphogenesis could be observed, in the mutant, although its rate of
      cell proliferation remained unchanged. This phenotype was associated with a
      significant decrease in the activation of Akt/PKB and PLCgamma-1, as compared to
      the wild type, while the activation of MAPK/Erk was less affected. Requirement
      for PI 3-kinase signaling in embryoid body differentiation was demonstrated by
      specific inhibitors. Akt/PKB activation was abrogated by wortmannin in short-term
      experiments. In long-term cultures Ly294002 inhibited the differentiation of ES
      cells into embryoid bodies. Our data demonstrate that for early epithelial
      differentiation FGF signaling is required through the PI 3-kinase-Akt/ PKB
      pathway.

PMID- 10949930
TI  - Adenovirus E4orf4 protein interacts with both Balpha and B' subunits of protein
      phosphatase 2A, but E4orf4-induced apoptosis is mediated only by the interaction
      with Balpha.
AB  - Adenovirus E4orf4 protein is a multifunctional viral regulator, which is involved
      in down regulation of virally-modulated signal transduction, in control of
      alternative splicing of viral mRNAs, and in induction of apoptosis in transformed
      cells. It has been previously shown that E4orf4 interacts with protein
      phosphatase 2A through the phosphatase Balpha subunit. It was further shown that
      PP2A is required for performing the various E4orf4 functions. We report here that
      E4orf4 interacts with multiple isoforms of the PP2A-B' subunit, as well as with
      Balpha. We map the interaction sites of the B subunits on E4orf4 and show that
      they overlap but are not identical. We identify a dominant negative E4orf4
      mutant, which disrupts the PP2A holoenzyme. We show that induction of apoptosis
      by E4orf4, which we previously reported to require the interaction with Balpha,
      is not affected by the interaction with B'. Our results suggest that the
      interaction of E4orf4 with various PP2A subpopulations may mediate the different
      E4orf4 functions.

PMID- 10949931
TI  - Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen
      receptor-negative lung cancer cells.
AB  - Although originally synthesized as an anti-estrogen, tamoxifen (Tam) was found to
      be able to inhibit proliferation of estrogen receptor (ER)-negative cancer cells
      in vitro. However, the molecular basis of such ER-independent growth inhibition
      is largely unknown. We have previously demonstrated that Tam induces p21WAF1 and
      p27KIP1 expression in human lung cancer cells which lack ER-alpha and -beta. We
      found that Tam induced p21WAF1 expression via transcriptional activation. In
      order to determine the molecular mechanism responsible for p21WAF1 induction by
      Tam, we performed a deletion analysis on the p21WAF1 promoter. The minimal region
      in the p21WAF1 promoter required for Tam-activated induction was mapped to a
      contiguous stretch of 10 bp located 83 bases upstream of the transcription
      initiation site. Our results showed that transcription factor Sp1 and Sp3 bound
      to this GC-rich region and mutation of Sp1-binding sites dramatically attenuated
      Tam-induced p21WAF1 promoter activity. We also tried to elucidate the signaling
      pathway that mediated the activation of p21WAF1 by Tam. Inhibition of mitogen
      activated protein kinase pathways did not block Tam-induced p21WAF1. Similarly,
      protein kinase C inhibitor calphostin C could not suppress Tam-induced p21WAF1.
      Conversely, pretreatment of a specific protein kinase A inhibitor H89
      significantly attenuated the induction of p21WAF1 by Tam. Furthermore, PKA
      activators forskolin and dibutyryl-cAMP activated p21WAFI promoter activity and
      increased p21wAF1 protein level in lung cancer cells. Taken together, these
      results demonstrate that Tam activates the p21WAF1 promoter via Sp1-binding sites
      and suggest that PKA may be involved in the induction of p21wAF1 by Tam in ER
      negative lung cancer cells.

PMID- 10949932
TI  - LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis.
AB  - Using an expression cloning system to discover novel genes involved in apoptosis,
      we identified a 326 bp bone marrow cDNA fragment (termed Je2) that suppresses,
      upon transfection, CD95-mediated apoptosis in Jurkat T cells. Sequence homology
      revealed that Je2 maps to 3p21.3, to an intronic region of the candidate TSG LUCA
      15 locus. It represents, in fact, an antisense transcript to the 3'-UTR of two
      novel splice variants of this gene. Overexpression of sequence representing one
      of these splice variants (a 2.6 kb cDNA termed Clone 26), inhibited proliferation
      of Jurkat cells and sensitized them to CD95-mediated apoptosis. This study
      therefore implicates the LUCA-15 gene locus in the control of apoptosis.

PMID- 10949933
TI  - The polo-like kinase Plx1 prevents premature inactivation of the APC(Fizzy)
      dependent pathway in the early Xenopus cell cycle.
AB  - Members of the polo-like family of protein kinases have been involved in the
      control of APC (anaphase-promoting complex) during the cell cycle, yet how they
      activate APC is not understood in any detail. In Xenopus oocytes, Ca2+-dependent
      degradation of cyclin B associated with release from arrest at second meiotic
      metaphase was demonstrated to require the polo-like kinase Plx1. The aim of the
      present study was to examine, beyond Ca2+-dependent resumption of meiosis, the
      possible role of Plx1 in the control of cyclin degradation during the early
      mitotic cell cycle. Plx1 was found to be dispensable for MPF to turn on the
      cyclin degradation machinery. However, it is required to prevent premature
      inactivation of the APC-dependent proteolytic pathway. Microcystin suppresses the
      requirement for Plx1 in both Ca2+-dependent exit from meiosis, associated with
      degradation of both cyclin B and A downstream of CaMK2 activation, and prevention
      of premature APC(Fizzy) inactivation in the early mitotic cell cycle. These
      results are consistent with the view that Plx1 antagonizes an unidentified
      microcystin-sensitive phosphatase that inactivates APC(Fizzy).

PMID- 10949934
TI  - Different impact of p53 and p21 on the radiation response of mouse tissues.
AB  - Mammalian tissues differ dramatically in their sensitivity to genotoxic stress,
      although the mechanisms determining these differences remain largely unknown. To
      analyse the role of p53 and p21 in determination of tissue specificity to DNA
      damage in vivo, we compared the effects of gamma radiation on DNA synthesis on
      whole-body sections of wild type, p53-deficient and p21-deficient mice. A
      dramatic reduction in 14C-thymidine incorporation after gamma irradiation was
      observed in the majority of rapidly proliferating tissues of wild type and p21-/-
      but not in p53-/- mice, confirming the key role of p53 in determination of tissue
      response to genotoxic stress in vivo and suggesting that p53-mediated inhibition
      of DNA synthesis does not depend on p21. Rapid radiation induced p53-dependent
      apoptosis was mapped to the areas of high levels of p53 mRNA in radiation
      sensitive tissues analysed (white pulp in the spleen and bases of crypts in small
      intestine), indicating that p53 regulation at the mRNA level is a determinant of
      cellular sensitivity to genotoxic stress. High p53 mRNA expression is inherited
      as a recessive trait in cell-cell hybrids suggesting the involvement of a
      negative control mechanism in the regulation of p53 gene expression.

PMID- 10949935
TI  - A novel zinc finger gene is fused to EWS in small round cell tumor.
AB  - Ewing sarcoma family of tumors share recurrent translocations that fuse EWS from
      22q12 to five different members of transcription factors namely FLI-1, ERG, ETV1,
      E1AF and FEV. Different classes of DNA binding proteins, ATF1, WT1 and CHOP are
      fused to EWS generating distinct tumor phenotypes: clear cell sarcoma,
      desmoplastic small round cell tumor, and myxoid liposarcoma, respectively. We
      have cloned a novel gene located at 22q12 fused to EWS by a submicroscopic
      inversion of 22q in a small round cell sarcoma showing a translocation
      (t(1;22)(p36.1;q12). The gene, designated ZSG (Zinc finger Sarcoma Gene), is a
      putative Cys2-His2 zinc finger protein which contains a POZ transcriptional
      repressor-like domain at the N-terminus. The rearrangement involves intron 8 of
      EWS and exon 1 of ZSG creating a chimeric sequence containing the transactivation
      domain of EWS fused to zinc finger domain of ZSG. This product lacks the
      transcriptional repressor domain at the N-terminus of ZSG. A rearrangement of the
      second ZSG allele was also found in tumor cells. This is the first example of an
      intra-chromosomal rearrangement of chromosome 22, undetectable by cytogenetics,
      activating EWS in soft tissue sarcoma.

PMID- 10949936
TI  - Detection of spatial localization of Hst-1/Fgf-4 gene expression in brain and
      testis from adult mice.
AB  - HST-1, a member of the fibroblast growth factor (FGF) family (FGF-4), has been
      shown to be a signaling molecule whose expression is essential for embryonic
      development. However, HST-1/FGF-4 expression has not been detected or reported in
      adult tissues so far analysed. To investigate whether there is a possible role of
      HST-1/FGF-4 in adult stage, we have carried out a highly sensitive RT-PCR
      analysis of Hst-1/Fgf-4 gene expression in adult mice tissues. Results show Hst
      1/Fgf-4 gene expression in the nervous system, intestines, and testis of normal
      adult mice. In situ hybridization technique was used to localize Hst-1/Fgf-4 gene
      expression in the cerebellum and testis from 10-week-old mice. Cell type-specific
      gene expression was detected: Purkinje cells in the cerebellum and Sertoli cells
      in testis. These findings suggest that the Hst-1/Fgf-4 gene also plays an
      important role in adult tissues, and may offer insights into the biological
      significance of HST-1/FGF-4 in cerebellar and testicular functions.

PMID- 10949937
TI  - The integrin-linked kinase (ILK) suppresses anoikis.
AB  - Disruption of integrin-extracellular matrix interactions in normal epithelial
      cells induces apoptosis, a process termed anoikis. Reduced sensitivity to anoikis
      appears to be an important hallmark of oncogenic transformation, particularly in
      the process of metastasis. Several pathways have been implicated in the
      suppression of anoikis, however, the events which take place proximal to the
      integrin receptors remain unclear. Integrin-linked kinase (ILK) is an integrin
      interacting protein kinase which has been identified as a potential PDK-2, as it
      is capable of phosphorylating PKB/Akt on Ser-473, and stimulating its activity.
      Here, we show that ILK activity is stimulated upon adhesion of SCP2 mouse mammary
      epithelial cells to fibronectin, and inhibited in suspended cells. Overexpression
      of ILK in the anoikis-sensitive SCP2 cells results in a profound inhibition of
      anoikis, as determined by annexin V binding and activation of caspases 8 and 3.
      This effect is reversible by the transfection and expression of a dominant
      negative, kinase deficient ILK (ILK KD), as well as by a dominant negative
      PKB/Akt (PKB AAA). On the other hand, transfection of a dominant negative form of
      FAK (FRNK) failed to reverse the suppression of anoikis by ILK. Furthermore,
      inhibition of ILK activity induced anoikis in two anoikis-resistant human breast
      cancer cell lines. These findings suggest that ILK plays a major role in the
      suppression of anoikis.

PMID- 10949938
TI  - p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive
      events in human glioblastoma.
AB  - P16 and P14ARF are two tumor suppressors encoded by the locus ink4a-arf which is
      frequently deleted in human tumors. Recent experiments performed with mouse
      embryonic fibroblasts have shown that P14ARF is an upstream regulator of the P53
      pathway. This raises the question as to whether in human tumors the loss of
      p14arf and mutation of p53 are mutually exclusive events which segregate with
      genetic alterations at other loci. To examine this question we performed a
      multigenic analysis on 29 gliomas. We analysed p53 and p14arf in relation with
      five other genetic loci encoding the most frequently mutated genes in human
      gliomas: cdkn2a, mdm2, egfr, pten and the chromosomal regions 10q23.3 and 10q25
      26. Our study shows for the first time that p53 mutations and p14arf deletions
      appear mutually exclusive in human glioblastoma, suggesting that they may be
      functionally redundant in glioma tumorigenesis. The P53 pathway is, therefore,
      disrupted in 81.8% of malignant gliomas (WHO grades III and IV), either by
      mutation of the p53 gene (31.8%) or by p14arf deletion (54.5%). These tumors
      further showed MDM2 overexpression (9.1%), egfr oncogene amplification/egfr
      overexpression (50%), pten mutations (27.3%) and loss of heterozygosity (LOH) at
      the chromosomal regions 10q23.3 (86.4%) and 10q25-26 (100%). These alterations
      did not segregate with p53 mutations or p14arf deletions, while p14arf and cdkn2a
      were always deleted.

PMID- 10949939
TI  - Evidence for a function of CtBP in epithelial gene regulation and anoikis.
AB  - Previously, we reported that adenovirus E1a protein behaves as a tumor suppressor
      in human cells. It apparently functions by transcriptionally inducing an array of
      epithelial cell adhesion genes, while repressing other cell-type specific genes,
      thus producing an epithelial phenotype. Concomitantly, the cells become sensitive
      to anoikis (apoptosis of epithelial cells detached from extracellular matrix),
      potentially causing tumor suppression. E1a protein interacts with the nuclear
      acetylases p300, CBP and P/CAF, and also with the co-repressor protein CtBP. In
      this study, we have determined the role of these interactions in E1a's phenotypic
      effects on human tumor cells. The results indicate that E1a's interaction with
      CtBP activates at least three epithelial cell adhesion gene promoters. The E
      cadherin repressor appeared to be the CtBP-interacting protein delta EF1/ZEB,
      which bound the ras-repressible E-boxes of the E-cadherin promoter. The E1a-CtBP
      interaction also contributed to anoikis-sensitization. E1a's interactions with
      the nuclear acetylases conferred epithelial morphologies but did not activate
      epithelial genes. These latter interactions did not sensitize tumor cells to
      anoikis but nevertheless conferred tumor suppression. These results implicate
      CtBP as an antagonist of the epithelial phenotype and anoikis. They also indicate
      a new but undefined role for nuclear acetylases in maintaining the transformed
      phenotype.

PMID- 10949940
TI  - Prediction and statistical evaluation of speech recognition test scores.
AB  - A speech test evaluation and presentation system is described. The test
      presentation subsystem has the flexibility and speed of live-voice testing while
      using recorded test materials. The speech test evaluation subsystem compares an
      individual subject's test performance on a monosyllabic word test with that of an
      average person with the same hearing loss. The elements needed to make such
      evaluations are discussed. Also, a trial of the procedure is described. The
      primary purpose of the trial was to obtain data that would provide a basis for
      statistical probability statements about individual monosyllabic word test
      results obtained in clinical settings. Data were collected from three audiology
      clinics in three different types of settings. Except for a few cases with highly
      asymmetric speech scores, all nonconductive hearing losses were included. Subject
      ages ranged from 8 to 92 years. Importance-weighted average pure-tone hearing
      losses ranged from 0.4 to 97.6 dB HL. Fifty-word recognition scores and
      audiograms for 2609 ears were included in the main analysis. Twenty-five-word
      recognition scores and audiograms for another 932 ears from one clinic were used
      in a subsidiary analysis. Results indicated that distributions of absolute speech
      recognition scores in hearing-impaired samples are highly skewed. However, after
      transformation of the scores into rationalized arcsine units (rau), the
      differences between individual subject scores and scores predicted from the
      audiogram were reasonably well described by the normal distribution. The standard
      deviation of this distribution of differences, for the data combined across the
      three audiology clinics, was approximately 13 rau.

PMID- 10949941
TI  - Attention effects on distortion-product otoacoustic emissions with contralateral
      speech stimuli.
AB  - This study investigated the effect of selective attention on the distortion
      product otoacoustic emission (DPOAE) level through the use of environmentally
      meaningful, contralateral auditory stimuli. Four different conditions were used
      for measurement: quiet, contralateral noise, contralateral speech (unattended),
      and contralateral speech (attended). A statistically significant suppression
      effect for both the noise and speech conditions was found. However, there was no
      support for an auditory selective attention effect on the distortion-product
      amplitude.

PMID- 10949942
TI  - Interactions among variables in the P300 response to a continuous performance
      task.
AB  - This study investigated the effect of variable interstimulus intervals (ISIs) on
      behavioral reaction time (RT) and on the latency and amplitude of the auditory
      P300 using an auditory continuous performance task (ACPT) paradigm. Twenty
      subjects were instructed to respond to common stimuli and ignore a rare stimulus.
      Common stimuli were 1000-, 1500-, and 2000-Hz pure tones. The rare stimulus was a
      250-Hz pure tone. ISIs of 1, 2, and 4 seconds were used for this investigation. A
      significant correlation between ISI, reaction time, P300 latency, correct
      rejections, and false alarm rates was found. A significant correlation between
      P300 latency, P300 amplitude, correct rejections, and false alarm rates was also
      observed. Likewise, a statistically significant increase in reaction time (RT)
      was observed as ISI increased. The ACPT paradigm in conjunction with the auditory
      P300 response can measure both behavioral and electrophysiologic changes that
      occur during active auditory attention and auditory cognitive processing tasks.

PMID- 10949943
TI  - Mismatch negativity to acoustic differences not differentiated behaviorally.
AB  - Mismatch negativity (MMN) reportedly reflects the neurophysiologic detection of
      acoustic differences, rather than the phonemic categorization of speech sounds.
      The purpose of the present study was to determine if it is elicited by speech
      contrasts that are acoustically different but are not differentiated by listeners
      in behavioral tasks. Experimental stimuli were drawn from a synthetically
      generated continuum that varied in place of articulation from /da/ to /ga/.
      Contrasts used to elicit MMN were (a) the continuum endpoints, (b) the two-step
      contrast that straddled each listener's categorical boundary, and (c) a within
      category contrast that was not behaviorally differentiated by any of the
      listeners. MMN responses were elicited by all three experimental contrasts. It
      appears that MMN may be an index of the neurophysiology underlying the ability or
      inability to discriminate the acoustic parameters necessary for speech
      perception, rather than a neurophysiologic correlate of behavioral speech
      discrimination ability. However, limitations involving identification of MMN in
      the responses of individual listeners confounded this interpretation.

PMID- 10949944
TI  - Otoacoustic emissions in normal-cycling females.
AB  - The purpose of this study was to determine if the menstrual cycle influences the
      amplitude of transient (TEOAEs) and distortion-product (DPOAEs) otoacoustic
      emissions. Thirteen normal-hearing, normal-cycling females were monitored weekly
      for 12 weeks. TEOAE and DPOAE amplitudes were analyzed to determine if amplitude
      changes could be detected and correlated to phases of the menstrual cycle. No
      systematic amplitude changes were observed, demonstrating that evoked OAEs are
      unaffected by physiologic changes associated with the menstrual cycle.

PMID- 10949946
TI  - Complete nucleotide sequence and infectious cDNA clone of the RNA1 of a Chinese
      isolate of broad bean wilt virus 2.
AB  - The nucleotide sequence of the RNA1 of broad bean wilt virus 2 (BBWV2) isolate
      B935 has been determined from overlapping cDNA clones. It contains 5956
      nucleotides in length excluding the 3' terminal poly(A) tail and contains a
      single long open reading frame (ORF) of 5613 nucleotides extending from
      nucleotide 234 to 5846. A repeated motif has been found in the 5' non-coding
      region. The predicted polyprotein encoded by the long ORF is 1870 amino acid in
      length with a molecular weight of 210 K. Amino acid sequence comparisons between
      portions of the BBWV2 RNA1-encoded polyprotein and proteins encoded by several
      species in Comoviridae revealed the putative functions of BBWV2 RNA1-encoded
      proteins and the same general genetic organization as that of comoviruses and
      nepoviruses. Based on the determined sequence, full-length cDNA clone of RNA1
      designated as pU1FL was constructed. Together with transcripts from full-length
      cDNA clone of RNA2 (pU2FL), transcripts from pU1FL infected Chenopodium quinoa
      successfully.

PMID- 10949945
TI  - T-Ag inhibits implantation by EC cell derived embryoid bodies.
AB  - When introduced into EC cells of a blastocyst, polyomavirus (Py) T-Ag results in
      mice mosaic for T-Ag but otherwise essentially normal. It had been reported that
      SV40 T-Ag does not inhibit differentiation of F9 EC cells, but did inhibit
      endogenous retrovirus (ERV) production. We therefore sought to determine if Py T
      Ag had any affect on EC derived embryoid body implantation onto mouse placenta.
      F9 EC cells were selected for T-Ag maintenance. Like the SV40 transformed cells,
      we show that these Py T-Ag selected EC cells no longer express IAP transcripts
      following differentiation into embryoid bodies. Normal and Py T-Ag selected F9
      cells were differentiated into embryoid bodies then implanted into pseudopregnant
      mice. We observe, that normal F9 derived embryoid bodies underwent the initial
      stages of implantation whereas the Py T-Ag selected embryoid bodied did not
      implant. The implications of this observation with respect to trophectoderm and
      ERV function are discussed. We examine the idea that ERVs may be a required
      element for normal embryo implantation.

PMID- 10949948
TI  - Characterization of early region 4 of porcine adenovirus serotype 5.
AB  - To locate the E4 region on the genome of the HNF-70 prototype strain of the
      porcine adenovirus serotype 5 (PAdV-5), 4.5 kb at the extreme right end was
      sequenced. This area had 11 open reading frames (ORFs) on the left strand
      encoding more than 50 amino acids (aa). A Genbank homology search indicated that
      8 of these ORFs were unique to PAdV-5. ORF5:253 aa, ORF6:245 aa and ORF11:146 aa
      showed similarities to known mammalian and avian adenovirus E4 ORFs. The putative
      E4 promoter sequences were also identified. Two TATA boxes, several GC boxes and
      two typical CCAAT boxes were located within this region. The presence of several
      potential poly-adenylation signals and the number of E4 transcripts detected by
      Northern blot analysis suggested the possibility of a complex mRNA transcription.

PMID- 10949947
TI  - n-Butyrate mediated inhibition of papovavirus DNA replication in vivo and in cell
      culture: a mechanistic approach.
AB  - n-Butyrate, an inhibitor of G1-to-S transition inhibits papovavirus DNA
      replication in cell culture. To explore the efficacy of n-butyrate in vivo and to
      better understand its mechanism, we studied the effect of n-butyrate on viral DNA
      replication in mice acutely infected with polyomavirus and in the papovavirus
      infected cells in culture. Newborn mice treated with n-butyrate stop growing and
      become runted. When infected with polyomavirus, these mice show a strong overall
      inhibition of viral DNA. However, a notable exception to this was the continued
      viral DNA replication in the differentiated mouse keratinocytes and renal
      epithelial cells as determined by in situ hybridization. n-Butyrate significantly
      inhibited viral DNA replication in the cultured IDL cells, and in polyomavirus
      infected C2C12 myoblasts based on Southern blot analysis and in situ
      hybridization. DNA polymerase alpha (but not DNA polymerase beta) and the
      characteristic nuclear expression of PCNA were both inhibited in the n-butyrate
      treated IDL and C2C12 cells. n-Butyrate, therefore, inhibited host and viral DNA
      synthesis in the undifferentiated cells.

PMID- 10949949
TI  - Domains of human respiratory syncytial virus P protein essential for
      homodimerization and for binding to N and NS1 protein.
AB  - In this report we used the two-hybrid technique to test for binding among human
      respiratory syncytial virus (HRSV) proteins involved in the control of viral
      replication. Besides the expected positive interactions for the nucleoprotein (N)
      with itself and the phosphoprotein (P), our results also demonstrated P-P
      interaction and P-NS1 binding. However, no interactions have been detected for
      the matrix protein M, the M2-1 and the M2-2 protein neither with each other nor
      in combination with the phosphoprotein P, the nucleoprotein N or the non
      structural protein NS1. While the N-P interaction was abolished by N- and C
      terminal deletions of both partners, C-terminal deletion mutants of P were still
      able to form homodimers. In contrast, the C-terminal region of P turned out to be
      essential for binding of NS1. N-N interaction was disrupted by any of the N- and
      C-terminal deletions.

PMID- 10949950
TI  - Capsid protein diversity among Norwalk-like viruses.
AB  - We have determined the complete capsid gene sequence of 20 Norwalk-like viruses
      (NLVs) collected predominantly from outbreaks in the UK between 1989 and 1996.
      These comprised nine genogroup I and eleven genogroup II strains. Phylogenetic
      analysis of these and 15 published sequences suggest seven genomic sub-groups
      within genogroup I, including three previously described. In genogroup II, eight
      sub-groups were apparent, of which four were novel. Amino acid identities between
      strains of distinct genogroups ranged from 37 to 44% while varying between 61 and
      100% for strains within a genogroup. Separate phylogenetic analyses of the N
      terminus and central variable region of the capsid showed good correlation.
      Sequence divergence between strains was greatest within the central variable
      region, with amino acid sequence identities as low as 28% within a genogroup.
      These 15 genomic sub-groups provide a framework for further investigations of
      genetic and antigenic relationships within this calicivirus clade.

PMID- 10949951
TI  - Sequence analysis of Pns11, a nonstructural protein of rice gall dwarf virus, and
      its expression and detection in infected rice plants and vector insects.
AB  - The nucleotide sequence of genome segment S11 of rice gall dwarf virus (RGDV), a
      member of Phytoreovirus, was determined. The segment encodes a putative protein
      of 40 kDa that exhibits approximately 37% homology at the amino acid level to the
      nonstructural proteins Pns10 of rice dwarf and wound tumor viruses, which are
      other members of Phytoreovirus. A band of a protein with an apparent molecular
      mass of 40 kDa was specifically detected in an analysis of cells transfected with
      S11 cDNA. An antiserum raised against this protein reacted with a protein of
      approximately 40kDa after fractionation by SDS-PAGE of materials prepared from
      infected plants and from viruliferous vector insects. However, the antiserum did
      not react with purified viral proteins. These results suggest that S11 encodes a
      nonstructural protein of RGDV. This protein was named Pns11.

PMID- 10949952
TI  - Both point mutation and RNA recombination contribute to the sequence diversity of
      citrus viroid III.
AB  - Field-grown citrus trees often harbor complex mixtures of 4-5 different viroid
      species, and the presence of citrus viroid III (CVd-III) has been shown to reduce
      the rate of tree growth without inducing disease. To more fully define the
      structure of its quasi-species, we have examined nine citrus viroid complexes for
      the presence of previously undescribed sequence variants of CVd-III. Analysis of
      86 full-length cDNAs generated from these nine viroid complexes by RT-PCR
      revealed the presence of 20 new CVd-III variants. Chain lengths ranged from 293
      297 nucleotides, and sequence changes were confined largely to the lower portions
      of the central conserved region and variable domain. The previously described
      variants CVd-IIIa (297 nt) and CVd-IIIb (294 nt) were clearly predominant, but
      phylogenetic analysis indicated that certain isolates may contain representatives
      of two additional fitness peaks. At least one group of CVd-III variants appears
      to have arisen as a result of RNA recombination. Populations recovered from
      diseased/declining trees were the most diverse, but even dwarfing isolates
      originating from old line Shamouti trees showed considerable variability.

PMID- 10949954
TI  - Nucleotide sequence analysis of the entire coding regions of virulent and
      avirulent strains of viral haemorrhagic septicaemia virus.
AB  - The complete nucleotide sequences of the six open reading frames (N, P, M, G, NV
      and L) and the intergenic regions were determined for two virulent freshwater
      strains and two avirulent marine strains of viral haemorrhagic septicaemia virus
      (VHSV). Sequence analysis of 10,845 nucleotides revealed > 97.2% nucleotide
      sequence similarity and > 98.6% amino acid similarity, confirming the close
      genetic relationship between marine and freshwater strains of VHSV. Moreover, as
      few as 10 amino acid substitutions were identically substituted between the
      marine and freshwater strains investigated. The results of this study suggest
      that only a limited number of amino acid residues may be involved in the
      determination of VHSV virulence for salmonids and further highlights the
      potential risk that marine strains may pose to freshwater aquaculture.

PMID- 10949953
TI  - Comparative nucleotide sequence analyses of the entire genomes of B95a cell
      isolated and vero cell-isolated measles viruses from the same patient.
AB  - Experimental infection of monkeys with the IC-B strain of measles virus (MV),
      which was isolated in marmoset B lymphoblastoid B95a cells from an acute measles
      patient, caused clinical signs typical for measles, while infection by the IC-V
      strain isolated in African green monkey kidney Vero cells from the same patient
      did not cause any clinical signs in infected monkeys. The IC-B strain replicated
      only in B95a cells, whereas the IC-V strain replicated in both B95a and Vero
      cells (3,6). To clarify which gene or mutation(s) was responsible for the
      difference in these phenotypes, the nucleotide sequences of the entire genomes of
      the IC-B and IC-V strains were determined. Comparative nucleotide sequence
      analyses revealed only two nucleotide differences, one in the P/V/C gene and the
      other in the M gene, predicting amino acid differences in the P, V and M proteins
      and a 19 amino acid deletion in the C protein of the IC-V strain. The truncation
      in the C protein was confirmed for the IC-V strain by immunoprecipitation using
      the C protein specific antiserum. No nucleotide difference was found in the
      envelope H gene. These results indicated that nucleotide difference(s) in the
      P/V/C or/and M gene, and not H gene, was responsible for the different cell
      tropism and pathogenicity of MV in this case.

PMID- 10949955
TI  - Detection of hepatitis B virus surface antigen mutants in paraffin-embedded
      hepatocellular carcinoma tissues.
AB  - The antigenic "a" determinant of the human hepatitis B virus surface antigen
      (HBsAg) is highly conserved and involved in inducing neutralizing antibody.
      Mutations on this determinant have been associated with the hepatitis B virus
      (HBV) escape from vaccination but are also found in chronic HBV carriers, but
      their involvement in liver diseases including hepatocellular carcinoma (HCC) is
      unclear. To investigate the possible liver disease-associated role of HBsAg
      mutants, their incidence was analyzed in 11 paraffin embedded HCC tissues using
      an improved DNA extraction method. Mutations on the "a" determinant (Thr126Ser,
      Gly145Arg, a double mutant Thr126Ser/Gln129Asn, Met 133Leu and Thr140Ile) were
      identified in 5 samples while the wild type sequence was found in 2 others.
      Future characterization of these HCC-associated HBsAg mutants should provide new
      insights on their role in the pathogenesis of HCC.

PMID- 10949956
TI  - Nucleotide sequence of the structural protein-encoding region of foot-and-mouth
      disease virus A22-India.
AB  - Nucleotide sequence of the structural protein-encoding region of foot-and-mouth
      disease virus (FMDV) A22-India 17/77 was determined using non-radioisotopic
      technique. Comparison of nucleotide and deduced amino acid sequence with A22-Iraq
      24/64 revealed 175 synonymous (silent) and 42 non-synonymous nucleotide changes
      resulting in 34 amino acid substitutions along the capsid proteins (VP1-VP4). Out
      of the 4 structural proteins VP4 is highly conserved. The highly variable and
      immunodominant protein VP1 showed 47% of the total amino acid substitutions. VP2
      and VP3 contain 38.2% and 14.7% of the amino acid substitutions, respectively.
      The VP1-based phylogenetic analysis of 18 different type A viruses including A22
      India 17/77 divided them in to two broad genetic groups (Asian and European/South
      American), and each group is further subdivided in to two separate genotypes. A22
      India 17/77, A22-Iraq 24/64 and A22-Azerbaijan/65 formed one genotype and the 4
      Chinese strains formed a separate genotype in the Asian group of viruses. In the
      European/South American group, A-Argentina/87 represents one genotype and the
      remaining 10 strains formed the second genotype in this group.

PMID- 10949957
TI  - Influence of deviant friends on delinquency: searching for moderator variables.
AB  - Three categories of potential moderators of the link between best friend's
      deviancy and boys' delinquency during early adolescence were investigated:
      personal (i.e., disruptiveneness profile during childhood, attitude toward
      delinquency), familial (i.e., parental monitoring, attachment to parents), and
      social (i.e., characteristics of other friends). Best friend's and other friends'
      deviancy were assessed during preadolescence through the use of peer ratings.
      Potential moderators were assessed at the same age period with teacher ratings or
      self-reports. Finally, delinquent behaviors were assessed at ages 13 and 14, as
      well as age 10 for control purposes, with self-reports. Results showed that boys'
      disruptiveness profiles during childhood, attachment to parents, and attitude
      toward delinquency moderated the link between best friend's deviancy and later
      delinquent behaviors. Other friends' deviancy and parental monitoring had main
      effects but no moderating effects. These results help clarify the conditions
      under which exposure to a deviant best friend can influence boys' delinquent
      behaviors. They also help to reconcile different theoretical explanations of the
      role of deviant friends in the development of delinquency.

PMID- 10949958
TI  - Do positive self-perceptions have a "dark side"? Examination of the link between
      perceptual bias and aggression.
AB  - The hypothesis that positive self-perceptions may have a "dark side" was
      investigated in the present study by examining the relationship between
      positively biased self-perceptions and aggression. Ratings of actual and
      perceived social acceptance of third-grade (n = 278), fourth-grade (n = 260), and
      fifth-grade (n = 321) students were compared to form a measure of perceptual
      bias. Peers provided nominations for overt and relational aggression. Gender
      differences were found for aggression (males were more overtly and relationally
      aggressive than females) but not perceptual bias. African-American children held
      more positive perceptions of their social acceptance and were perceived by peers
      as more aggressive than Caucasian children. Even after controlling for the
      effects of gender and ethnicity, more positively biased perceptions were
      associated with more peer nominations for overt and relational aggression.
      Contrary to an optimal range of bias hypothesis, even moderately positive self
      perceptions were associated with elevated levels of aggression.

PMID- 10949959
TI  - Emotional expressiveness during peer conflicts: a predictor of social
      maladjustment among high-risk preschoolers.
AB  - Preschool boys' emotional displays during conflicts with mixed-sex peers were
      related to individual differences in peer sociometric status and teacher ratings
      of disruptive behavior. Participants were 60 4- to 5-year old boys from low
      income families who were videotaped with a small group of classmates in a Head
      Start preschool classroom. Conflicts were identified and emotional displays were
      coded from videotape. Results indicated that conflicts were more negative in
      emotional tone at the end than at the beginning of the year. Furthermore,
      children tended to mirror each others' emotional displays at the end but not the
      beginning of the preschool year. In addition, gleeful taunting, a form of
      emotional aggression, more strongly predicted negative peer nominations and
      teacher ratings than anger, suggesting that anger may be a more socially accepted
      form of emotional expression during conflicts among preschool-age children.
      Implications and directions for future research and interventions are discussed.

PMID- 10949960
TI  - Stability of family interaction from ages 6 to 18.
AB  - Research has demonstrated the stability of juvenile offending during childhood
      and adolescence but generally has not focused on the continuity of family
      interactions associated with juvenile offending. The present report focused on
      the stability of several family interaction events and attributes (i.e., physical
      punishment, communication, supervision, positive parenting, and parent-child
      relationship) for a large sample of male adolescents and their primary
      caretakers, drawn from a multiyear longitudinal study that represented middle
      childhood through late adolescence (ages 6-18). We also assessed the impact of
      ethnicity, family composition, teenage motherhood, and youth delinquency on these
      interactions. Test-retest correlations and growth-curve analyses were used to
      assess relative and absolute stability of the interactions, respectively. As
      predicted, relative stability of family interaction was high. There was an
      absolute change in scores of physical punishment (decreased) compared to poor
      supervision and low positive parenting (both increased), whereas poor
      communication and bad relationship with the caretaker did not measurably change
      with age. Single-parent families and families with teenage mothers experienced
      significantly worse interactions over time than did families consisting of two
      biological parents present in the household. These findings are discussed in
      relation to the development of juvenile offending.

PMID- 10949961
TI  - Effects of stimulant medication treatment on mothers' and children's attributions
      for the behavior of children with attention deficit hyperactivity disorder.
AB  - Participants were 55 children with attention deficit hyperactivity disorder
      (ADHD) who were receiving ongoing treatment with stimulant medications and their
      mothers, and 31 children with ADHD who were beginning stimulant medication and
      their mothers. Mothers and children offered attributions for child behaviors that
      occurred when the child was medicated and not medicated. Mothers rated child
      compliance and prosocial behavior as more global and stable when the child was
      medicated and rated noncompliance, ADHD symptoms, and oppositional behavior as
      more externally caused, less global and stable, but more controllable by the
      child when the child was medicated. Children rated both their compliance and
      noncompliance as more controllable in the medicated condition. On a forced-choice
      measure, both mothers and children selected ability, effort, and task
      attributions for compliance more in the not-medicated condition, and pill-taking
      attributions more in the medicated condition. This was reversed for
      noncompliance, which was attributed more to effort, task, or ability in the
      medicated condition and more to not taking a pill in the not-medicated condition.
      The potential risks and benefits for parent-child interactions and children's
      self-perceptions of these medication-related differences in attributions are
      discussed.

PMID- 10949962
TI  - Specific life events and chronic experiences differentially associated with
      depression and anxiety in young twins.
AB  - Behavioral genetic analyses indicate that environmental influences associated
      with depression and anxiety are specific to each symptom type; however, this has
      not been tested specifically in children. Sixty-one (61) child twin pairs in
      which at least one twin had a very high anxiety or depression score, and 29
      nonanxious, nondepressed pairs were interviewed about life events and chronic
      stressors in the previous 12 months. Loss events, schoolwork stressors, family
      relationship problems, and friendship problems were all significantly associated
      with depression but not anxiety. Threat events were significantly associated with
      anxiety but not depression. Loss events and schoolwork stressors appeared to act
      as shared environment influences in that they made twin pairs resemble one
      another. Threat events, friendship problems, and family relationship problems
      were individual specific and accounted for differences within the pairs. These
      results clarify the associations between life events and depressive and anxious
      symptoms in children and adolescents and reveal specific associations previously
      unidentified in this age range.

PMID- 10949963
TI  - Structural, relative, and absolute agreement between parents' and adolescent
      inpatients' reports of adolescent functional impairment.
AB  - This study assessed agreement between parents' and adolescent inpatients' scores
      on caretaker and self-report versions of the Functional Impairment Scale for
      Children and Adolescents (FISCA and FISCA-SR). Self-report data describing
      impairment in eight domains were collected from 375 inpatients (M age = 15.0
      years, 55% females), with parent data available for 233 (62%). Confirmatory
      factor analysis demonstrated structural congruence between a hypothesized, three
      factor model, based on a prior study of the parent FISCA, and an observed model,
      based on responses to the FISCA-SR (GFI = .95). Correlations (measuring relative
      agreement) and paired comparisons of means (assessing absolute agreement)
      generally identified stronger agreement in "public" than "private" domains of
      impairment, and greater relative than absolute agreement in covert, antisocial
      domains.

PMID- 10949965
TI  - Rare-earth element distribution characteristics of biological chains in rare
      earth element-high background regions and their implications.
AB  - The rare-earth element (REE) contents of water and vegetables from two typical
      REE-high background regions and a normal region in Gannan, Jiangxi Province,
      indicated that the REE contents were significantly different from those of water
      and vegetables, respectively. The average values are 0.03 mg/L and 0.11 mg/L REE
      for water from regions A and B. As the REE contents of vegetables from region A
      are different from region B, it is suggested that there are a number of factors
      controlling the REE distribution from those among plants. By comparing with the
      normal region, the soluble REE contents of water from the REE-high background
      regions are higher than those of the normal region by factors of 18 and 68,
      respectively. The REE contents of most plants and crops from regions A and B are
      higher than those of the normal region. It is clear that the REEs are the
      indispensable elements of plants during their growing period. Why are the REE
      contents of some plants from regions A and B usually higher than those from the
      normal region? The answer is that the plants and crops have passively absorbed
      REE during their growth.

PMID- 10949964
TI  - Chronic toxicity of rare-earth elements on human beings: implications of blood
      biochemical indices in REE-high regions, South Jiangxi.
AB  - Blood analyses for rare-earth element (REE)-high background regions in South
      Jiangxi show that the population averages of many of the biochemical indices
      deviate markedly from normal values in the normal region. These deviations are
      thought to be caused by prolonged intake of REE through food chains in view of
      that the toxicity of other harmful metals such as Pb and Cd can be neglected
      because of their insignificant amounts in the environment. In comparison with the
      normal region, blood biochemical indices abnormal in the REE-high regions are
      manifested as low total serum protein (TSP), albumin, beta-globulin, glutamic
      pyruvic transitanase, serium triglycerides, and immunoglobulin, but high
      cholesterol. These deviations may be related to the REE concentration and
      composition of food chains, and are sex dependent. Certain blood indices (such as
      TSP) of different age groups in the LREE-high region indicate that the influence
      of REE on males is a one-way irreversible process, whereas females show a strong
      ability of restoration.

PMID- 10949966
TI  - Bacteriostatic effects of cerium-humic acid complex: an experimental study.
AB  - The bacteriostatic potency of the cerium-humic acid complex was evaluated by
      experimental measurement of this complex interaction with E. coli, Bacillus
      pyocyaneus, Staphylococcus aureus, Leuconostoc and Streptococcus faecalis, and by
      comparison bacteriostatic effects with the cerium-citrate complex. The
      experimental results indicated that the cerium-humic acid complex strongly
      inhibited growth of all five bacterial strains, and its diameter of
      bacteriostatic circles were more than 30 mm. The minimal bacteria-inhibiting
      concentration were 1 x 10(-3), 2 x 10(-3) and 1 x 10(-2) mol/L for E. coli and
      Bacillus pyocyaneus, Staphylococcus aureus, and Leuconostoc and Streptococcus
      faecalis individually, and the measured minimal bactericidal concentrations were
      2 x 10(-3) and 1 x 10(-2) mol/L for Bacillus pyocyaneus, E. coli, and
      Leuconostoc. To kill Staphylococcus aureus and Streptococcus faecalis, the
      concentration had to be more than 1 x 10(-20 mol/L. On the contrary, we found
      that cerium-citrate complex did not inhibit the growth of the above five
      bacteria, but stimulated bacterial growth. The completely different
      bacteriostatic results of two cerium complexes may hint that the association and
      chemical properties of the two complexes were different.

PMID- 10949967
TI  - Alterations in serum and brain trace element levels after antidepressant
      treatment. Part II. Copper.
AB  - We have studied the effect of chronic treatment with imipramine, citalopram, and
      electroconvulsive shock (ECS) on serum and brain copper levels in rats. Chronic
      treatment with citalopram and imipramine (but not ECS) significantly (approx 14%)
      decreased the serum copper level. Chronic treatment with both drugs did not alter
      the brain copper level. However, chronic ECS induced a significant increase (by
      36%) in the copper level in the hippocampus and also in the cerebellum (by 16%).
      In contrast to the zinc, where both pharmacologic and ECS treatment increased its
      hippocampal concentration, these two antidepressant therapy (drugs versus ECS)
      differ in their effect on brain copper level. These findings suggest that the
      mechanism by which copper is involved in ECS differs from that of any involvement
      in the action of the drugs studied.

PMID- 10949968
TI  - Selenium and malondialdehyde content and glutathione peroxidase activity in
      maternal and umbilical cord blood and amniotic fluid.
AB  - Placenta tissue may be a major source of lipid peroxidation products in
      pregnancy. It was proven that placental peroxidation activity increases with
      gestation. Selenium (Se), as an essential constituent of glutathione peroxidase
      (GSH-Px), takes part in the reduction of hydrogen peroxides and lipid peroxides.
      Malondialdehyde (MDA) is a major breakdown product split off from lipid
      peroxides. In this study, Se and MDA content and GSH-Px activity were measured in
      blood and plasma taken from 20 apparently healthy nonpregnant women between 19
      and 38 yr of age and from 115 unselected pregnant women between 17 and 45 yr of
      age (35 in the first trimester, 22 in the second trimester, 38 in the third
      trimester, and 20 within 2 d of delivery). Samples of umbilical cord blood and
      amniotic fluid were taken from women in the second and third trimesters and at
      delivery. The Se content was measured by atomic absorption spectrometry (AAS),
      plasma MDA concentration by thiobarbituric acid reaction, and Se-dependent GSH-Px
      spectrometrically. Blood and plasma Se contents of nonpregnant women were below
      those considered adequate, indicating low selenium intake. In comparison to
      nonpregnant women, pregnant women had significantly decreased whole-blood and
      plasma Se levels in the second and third trimesters and at delivery. The
      significant drop of whole-blood SeGSH-Px activity was observed in the first
      trimester of pregnancy and its lower activity was maintained until delivery. A
      significant drop in plasma SeGSH-Px activity occurred in the second trimester and
      attained the minimal level at delivery. The Se level and SeGSH-Px activity in
      maternal and umbilical cord blood were at similar levels. Amniotic-fluid SeGSH-Px
      activity was nondetectable or exceptionally low and its Se content remained
      unchanged during pregnancy. Plasma levels of MDA were significantly decreased in
      the second and third trimesters and at delivery. The fetal blood plasma at birth
      had a lower MDA level compared to the levels of MDA of their mothers at delivery.
      A low, but significant inverse correlation existed between blood SeGSH-Px
      activity and plasma MDA content and between plasma Se and plasma MDA contents
      during pregnancy. A significant decrease of Se and SeGSH-Px activities
      (antioxidant enzyme) in both blood and plasma suggests a possible drop in total
      antioxidant status during pregnancy. Elevated MDA plasma levels might be the
      result of increased lipid peroxidation in placental tissue during pregnancy.
      Index Entries: Selenium; glutathione peroxidase; malondialdehyde; pregnancy;
      umbilical cord blood; amniotic fluid.

PMID- 10949969
TI  - Copper and zinc concentrations and the activities of ceruloplasmin and superoxide
      dismutase in atherosclerosis obliterans.
AB  - The relationships among concentrations of copper and zinc, the oxidase activity
      of ceruloplasmin (Cp) in serum, and Cu,Zn-SOD (superoxide dismutase) activity in
      erythrocytes were investigated in men with atherosclerosis obliterans (AO) and a
      control group. The oxidase activity of Cp was measured with o-dianisidine
      dihydrochloride as a substrate, and Cu,Zn-SOD activity in erythrocytes by using
      the RANSOD kit. The lipid profile and uric acid concentration were determined in
      AO and control groups. The results showed higher copper and zinc concentrations
      in serum in the AO group (20.0+/-3.5 and 18.0+/-3.2 micromol/L, respectively) in
      comparison with the control group (15.6+/-2.3 and 14.7+/-1.9 micromol/L). The Cp
      activity in serum was higher in the AO group (174.2+/-61.8 U/L) than in the
      control group (93.7+/-33.9 U/L), and a significant difference was found in the
      activity of Cu,Zn-SOD in erythrocytes (2389+/-1396 and 1245+/-365 U/g Hb,
      respectively) between both groups. The activity of Cu,Zn-SOD was positively
      correlated with copper in the control group (r=0.73), but not in AO, and
      negatively with uric acid concentration (r= -0.63) in the AO group. The oxidase
      activity of Cp was correlated with copper, but not zinc, in AO and control groups
      (r> or =0.65). Negative correlation coefficients were calculated for uric acid
      and copper and zinc concentrations in the AO group (-r > or = 0.61). Increased
      copper concentrations and oxidase activity of Cp in serum in AO and the activity
      of Cu,Zn-SOD in erythrocytes could result from atherosclerotic disease,
      accompanied by chronic ischemia of a lower limb. These results suggest also that
      relationship between copper concentration and Cu,Zn-SOD activity in erythrocytes
      found in the serum of healthy subjects may be disturbed in pathologic conditions.

PMID- 10949970
TI  - Selenium and glutathione peroxidase mRNA in rat glioma.
AB  - The purpose of current study was to determine the step at which dietary selenium
      (Se) regulates the transcriptional expression of the gene for Se-glutathione
      peroxidase (Se-GPx) in rat brain and transplanted glioma tissue. Wistar rats were
      fed a Se-free diet or the same diet supplemented with 0.5, 2.0, and 4.0 mg Se/kg
      as sodium selenite for at least 3 wk. Then, the rats were transplanted with C6
      rat glioma cells into the right frontal lobe parenchyma. All rats were observed
      for 30 d, then tumor and contralateral brain tissue were excised and divided into
      three portions for purification of selenium content, for the assay of Se
      concentration, Se-GPx activity, and for Se-GPx mRNA. Se concentration and Se-GPx
      activity are increased with Se supplementation both in tumor tissue and
      contralateral brain tissue, and Se concentration in tumor is higher than that in
      contralateral brain tissue at each dietary Se content. Se-GPx mRNA of brain and
      tumor were probed with fragments from a rat Se-GPx cDNA in Northern blot
      analysis. There was significant differences of Se-GPx mRNA transcription in brain
      tumor tissue among each dietary group of the Se content, and the steady-state
      level of Se-GPx mRNA was markedly reduced by Se deficiency. These results suggest
      that dietary Se exerts its augmenting effect on Se-GPx gene transcription.

PMID- 10949971
TI  - Selenium, copper, and zinc indices of nutritional status: influence of sex and
      season on reference values.
AB  - The objective was to estimate the possible influence of season or season and sex
      on the selenium, glutathione peroxidase (GSH-Px), copper, zinc, and superoxide
      dismutase (SOD) values in plasma with a view to establishing reference values.
      For this purpose, 55 healthy volunteers (36 women and 19 men) were selected and
      their whole-blood samples were collected four times a year at the beginning of
      each season. In the population as a whole, no statistically significant seasonal
      differences were detected in copper, selenium, and GSH-Px values in plasma,
      whereas zinc and SOD values in plasma depended on the season. In general, the
      variability was higher among the women. In view of the differences detected
      according to sex and/or season in the parameters studied, we recommend taking
      samples from men and women and from different seasons to establish reference
      values.

PMID- 10949972
TI  - Influence of methionine and zinc on liver collagen in molybdenotic rats:
      relationship with lipid peroxidation.
AB  - Protective effects of methionine and zinc on collagenesis in the liver of
      molybdenotic rats have been studied during present investigations. Further, the
      relationship between two important pathobiological phenomena (viz. lipid
      peroxidation and collagenesis) has also been examined. Biological observations
      suggest that cotreatment with methionine only improves the growth of molybdenotic
      rats; however, the hepatosomatic index improved in rats supplemented with both
      methionine and zinc. Administration of methionine and zinc to molybdenum-fed rats
      decreased liver collagen. Results on urinary hydroxyproline support these
      observations. Lipid peroxidation was also inhibited in the liver of protected
      rats. We suggest that collagenesis can be controlled by inhibiting the generation
      of reactive oxygen species. An improvement in liver function in rats protected
      with methionine and zinc has also been suggested.

PMID- 10949973
TI  - Zinc may be a double-faced Janus to Down's syndrome patients.

PMID- 10949974
TI  - Multiantibiotic resistance of gram-negative bacteria isolated from drinking water
      samples in southwest Greece.
AB  - In this study we monitored the sensitivity of 239 gram-negative bacteria (of
      fecal and non-fecal origin), isolated from the old drinking water distribution
      network of Patras in southwestern Greece, to 20 antibiotic agents. Two methods
      were used to find the multiresistant bacteria (bacteria resistant to two or more
      antibiotics): the diffusion disk method and a serial dilution method. The gram
      negative bacteria tested were: Enterobacteriaceae (62), Pseudomonas (145),
      Vibrionaceae (24), Chromobacter (3), Acinetobacter (2) and others (4). The
      highest levels of antibiotic resistance were obtained for cephalothin (86.7%),
      ampicillin (77.5%) and carbenicillin (71%) followed by cefoxitin (55.4%) and
      cefuroxime (51.2%). Intermediate resistance levels were found for ticarcillin
      (31.3%), ceftizoxime (31.2%), chloramphenicol (30.3%), and cefotetan (25.2%). Low
      resistance levels were obtained for cefotaxime (17.9%), sulfisoxazole (15.2%),
      ceftriaxone (12.5%), tetracycline (11.9%), trimethoprim/sulfamethoxazole (7.4%)
      and piperacillin (2.4%). Overall 91.3% of the gram-negative bacteria isolated
      from drinking water were multiresistant. No resistant strains were found to
      quinolones, aminoglycosides, imipenem, aztreonam, ceftazidime or cefoperazone.
      The high antibiotic resistance rate of the isolated microorganisms from the
      Patras drinking water supply is discussed.

PMID- 10949975
TI  - A synthetic gamma-lactone group with beta-lactamase inhibitory and sporulation
      initiation effects.
AB  - Previous studies showed that some lactones have beta-lactamase inhibitory or
      antibacterial effects, others--like A-factor (a gamma-butyrolactone) and its
      derivatives--stimulate sporulation in Streptomyces griseus strains. Our
      experiments were aimed at exploring whether synthetic gamma-lactones had such
      effects. None of the seven gamma-lactones studied showed antibacterial activity,
      but two of them inhibited beta-lactamases isolated from various bacteria. These
      two gamma-lactones did not reduce colony formation of murine bone marrow cells in
      vitro, indicating that they were not toxic to proliferating mammalian cells. Four
      gamma-lactones, including the two inhibiting beta-lactamase, stimulated
      sporulation in the non-sporulating S. griseus bald 7 mutant. Further studies of
      gamma-lactones as potential inhibitors of beta-lactamase seem to be warranted.

PMID- 10949976
TI  - Effect of subminimal inhibitory concentrations of azithromycin on adherence of
      Pseudomonas aeruginosa to polystyrene.
AB  - Pseudomonas aeruginosa forms a bacterial biofilm by producing alginate when it
      adheres to mucosa or various medical devices. In this study, the effect of
      subminimal inhibitory concentrations (subMICs) of azithromycin (AZM) on the
      biofilm formation and in vitro adherence to polystyrene of 14 wild-type P.
      aeruginosa strains was studied. A total of 35 P. aeruginosa isolates from
      clinical specimens were used. Glycocalyx production was determined by the tube
      method, and bacterial adherence to the wells of flat bottom polystyrene tissue
      culture plates was estimated by the spectrophotometric method. Compared to the
      control, the adherence ability to polystyrene was inhibited by incubation with
      subMICs of AZM in a dose-dependent manner. These results support the findings of
      other investigators suggesting that AZM in subinhibitory concentrations may be
      useful in the prevention or treatment of biofilm-associated infections due to P.
      aeruginosa.

PMID- 10949977
TI  - Pharmacokinetic and pharmacodynamic interactions between intravenous
      ciprofloxacin and oral ferrous sulfate.
AB  - Changes in oral bioavailability and in vitro antimicrobial activity have been the
      focus of many previous interaction studies for metal cations and quinolones. This
      study is the first to examine the possibility of an interaction in the systemic
      circulation using ciprofloxacin and ferrous sulfate as representative
      interactants in a rat model, and to determine the changes, if any, in the
      pharmacokinetics and pharmacodynamics of the antibiotic. To minimize direct
      physical interaction in the gastrointestinal (GI) tract, the current study design
      required the male Sprague Dawley rats (220-240 g) to be dosed with 100 mg/kg of
      oral ferrous sulfate and 5 mg/kg of intravenous ciprofloxacin. Control animals
      received only intravenous ciprofloxacin. Blood and urine samples were collected
      over time for quantitation of ciprofloxacin independently by both HPLC (H) and
      microbiological (M) assays. Results showed that the disposition of ciprofloxacin
      in control animals was biexponential with a mean (+/-SD) terminal elimination
      half-life (t(1/2,lambda z)) of 0.93+/-0.30 h. A large apparent volume of
      distribution (V(d,lambda z): 6.96+/-1.56 L/kg) was observed. In addition,
      concentration vs. time profiles generated by both assays were similar. When the
      antibiotic was dosed with oral iron, parameter estimates generated by HPLC
      appeared to show a wider distribution and a longer elimination of ciprofloxacin;
      mean V(d,lambda z) and t(1/2,lambda z) estimates increased by 2- and 4-fold,
      respectively. Relative to controls, antibiotic exposure (AUC(0-infinity) was also
      significantly higher (p<0.05) in the presence of iron (1.89+/-0.15 vs. 1.00+/
      0.39 mg/h/L). A strong assay dependency was observed for ciprofloxacin
      concentrations observed post-distribution; the respective M/H ratios for AUC(0
      infinity) and urinary recovery were 1.1 and 0.9 for controls and 0.7 and 0.5 for
      animals receiving oral iron. This iron related reduction in antimicrobial
      activity was in clear contrast to the higher exposure and longer t(1/2,lambda z)
      of the antibiotic. In conclusion, concomitant oral iron dosing induced
      significant changes in the pharmacokinetics/pharmacodynamics of intravenous
      ciprofloxacin.

PMID- 10949978
TI  - Antimicrobial resistance of gram-negative isolates from intensive care units in
      Turkey: comparison to previous three years.
AB  - Resistance rates to selected antibiotics of gram-negative bacteria isolated from
      intensive care units (ICU) of 16 Turkish hospitals during 1998 were evaluated and
      compared to data from the previous 3 years. Antibiotic susceptibilities to
      imipenem, ceftazidime, ceftazidime-clavulanate, cefoperazone-sulbactam,
      ceftriaxone, cefepime, cefodizime, cefuroxime, piperacillin-tazobactam,
      ticarcillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined
      by Etest. A total of 1,404 isolates from 1,060 patients were collected, mainly
      from urinary and respiratory tracts. As in the previous 3 years, Pseudomonas spp.
      was the most frequently isolated gram-negative species (29.7%), followed by
      Escherichia coli, Acinetobacter and Klebsiella spp. Imipenem was the most active
      in vitro agent (73.4% susceptible), followed by ciprofloxacin (60.6%),
      cefoperazone-sulbactam (58.7%), cefepime (56.7%), piperacillin-tazobactam (55.0%)
      and amikacin (54.7%). In 1996, a decline in susceptibility rates of all
      antibiotics was evident. With the exception of imipenem, resistance to which
      remained stable, rates somewhat increased in 1997. In 1998, susceptibility to
      imipenem and cefepime remained stable, amikacin resistance tended to increase and
      susceptibility rates to other antibacterials showed a favorable increase. These
      results may in part be due to the implementation of a surveillance program and
      increased understanding of the magnitude of the resistance problem.

PMID- 10949979
TI  - Assessment of the susceptibility of Streptococcus pneumoniae to cefaclor and
      loracarbef in 13 countries.
AB  - Between July 1998 and July 1999, 2,644 clinical isolates of Streptococcus
      pneumoniae were collected from 27 study centers in 13 countries and their
      susceptibilities to penicillin, cefaclor and loracarbef were determined by E
      test" (AB BIODISK, Solna, Sweden). Overall, 96.3% of isolates were penicillin
      susceptible (79.8%) or -intermediate (16.6%) (MIC, < or = 1 microg/ml). Rates of
      penicillin-resistant S. pneumoniae isolation varied widely and were highest in
      the study centers tested in New Zealand (10.9%), Canada (10.0%), Mexico (9.1%)
      and the United States (5.1%). Low rates of penicillin-resistance were found in
      the study centers tested in Russia (0%), Turkey (0%), Brazil (0.5%), Germany
      (0.6%), Philippines (1.6%), Italy (2.1%), United Kingdom (2.3%), Australia (3.0%)
      and Poland (3.1%). Using recently published NCCLS interpretative breakpoints
      (M100-S10, 2000), 87.2% (median) of all isolates tested were cefaclor-susceptible
      and 87.8% (median) of all isolates tested were loracarbef-susceptible. Of the
      penicillin-susceptible S. pneumoniae isolates, 99.5% were susceptible to both
      cefaclor and loracarbef. Susceptibility to cefaclor and loracarbef was also
      retained by 30.8% and 32.9% of penicillin-intermediate isolates, respectively.
      These findings are in contrast to recent publications reporting lower cefaclor
      and loracarbef activities using non-validated interpretative criteria. In
      conclusion, rates of penicillin resistance among recent clinical isolates of
      pneumococci remain low in many centers worldwide. Cefaclor and loracarbef
      demonstrated excellent in vitro activity against recent clinical isolates of
      penicillin-susceptible and many isolates of penicillin-intermediate S.
      pneumoniae.

PMID- 10949980
TI  - Cefodizime in skin suction blister fluid and serum following a single intravenous
      or intramuscular dose in adult patients.
AB  - Cefodizime is a third generation cephalosporin for parenteral use. The
      pharmacokinetics of this cephem antibiotic were determined in serum and skin
      suction blister fluid (SBF) after intravenous (i.v.) or intramuscular (i.m.)
      administration of a single 1 g dose in 8 adult patients with normal renal and
      hepatic function who volunteered for the study. The concentration versus time
      curve showed a slower elimination rate from the extravascular compartment: the
      half-lives were 4.4+/-0.5 and 5.4+/-0.4 hours after i.v. and i.m. route
      respectively. The relatively long elimination half-life in SBF with a mean
      residence time of about 8 hours allows the use of cefodizime once-a-day for the
      treatment of infections due to sensitive pathogens.

PMID- 10949981
TI  - Gemifloxacin versus amoxicillin/clavulanate in the treatment of acute
      exacerbations of chronic bronchitis. The 070 Clinical Study group.
AB  - Six hundred patients were evaluated in this randomized, double-blind, double
      dummy, multicenter, parallel-group study comparing the efficacy and safety of
      gemifloxacin (320 mg once-daily for 5 days) and amoxicillin/clavulanate (500/125
      mg three-times daily for 7 days) for the treatment of acute exacerbations of
      chronic bronchitis (AECB). Of note, more than 90% of study participants had stage
      2 disease at study entry. The two drugs were found to be equally effective, with
      clinical success rates of 93.6% for gemifloxacin and 93.2% on
      amoxicillin/clavulanate (95% CI -3.9 to 4.6). Bacteriological success rates
      favored gemifloxacin (90.9% compared with 79.5% for amoxicillin/clavulanate; 95%
      CI -3.3 to 26.0); however, this difference was not statistically significant.
      Gemifloxacin and amoxicillin/clavulanate were both well tolerated. In summary,
      gemifloxacin was found to be well tolerated and effective for the treatment of
      AECB, suggesting it is well suited for empirical treatment of this common
      respiratory condition in the current clinical environment.

PMID- 10949983
TI  - Candidemia in pediatric surgery patients.
AB  - Candida spp. are the fourth leading cause of bloodstream infection. While the
      literature on neonatal candidemia is abundant, its prevalence in pediatric
      surgery cases is hardly mentioned. This study was carried out over a 5-year
      period to evaluate the prevalence of candidemia in pediatric surgery intensive
      care unit patients (ICU), and to examine both the neonatal and hospital risk
      factors for developing candidemia in comparison to control groups of patients
      with either no infection or with bacteremia, type and outcome of therapy. A total
      of 1,359 pediatric surgery patients admitted to the ICU and high dependency unit
      (HDU) were included in the study. Using relevant specimens from them, a
      microbiological survey was carried out on admission and weekly thereafter. Twenty
      five patients developed candidemia during the study period. Twenty-one of them
      were admitted to ICU. Nine were low birth weight and immature neonates. All 25
      patients had underlying disease, most involving the gastroentestinal tract and
      requiring surgical intervention. All patients had been given broad-spectrum beta
      lactam antibiotics with or without aminoglycosides and an anti-anaerobic drug
      prior to candidemia. The data show that patients who were not infected had very
      few risk factors that could predispose to candidemia. The bacteremic group of
      patients had more risk factors: mainly ICU stay, prior antibiotic therapy or GI
      surgery. The candidemia patients outnumbered these two groups in both neonatal
      and hospital risk factors. Twenty-three candidemia patients had received
      amphotericin B and 2 had fluconazole. Seventeen of them improved and the rest
      expired during therapy. Fourteen of the Candida isolated were C. albicans while
      the rest belonged to other Candida spp. dominated by C. parapsilosis. In
      conclusion, candidemia was infrequent in pediatric surgery patients. ICU stay, GI
      surgery and prior broad-spectrum antibiotic therapy were important risk factors.

PMID- 10949984
TI  - Candida meningitis in children: report of two cases.
AB  - Candida meningitis is rare in children. However reports have been increasing
      recently. We report two cases of meningitis caused by Candida species. The first
      case was a term male infant who was admitted at 14 days of age with the diagnosis
      of possible sepsis. He had received multiple courses of antibiotics without
      improvement. Later his cerebrospinal fluid (CSF) culture grew Candida tropicalis.
      The damage done by the infection was severe and the patient died. The second case
      was a 2-month old girl who was born at 34 weeks of gestation. She was admitted to
      the Neonatal Intensive Care Unit (NICU) and given antibiotics as prophylaxis.
      Despite this she developed recurrent episodes of fever that required multiple
      courses of antibiotics. After discharging her, she continued to have fever. Upon
      investigation, her blood and CSF grew Candida albicans. She was treated and
      responded to therapy.

PMID- 10949982
TI  - Comparison of efficacy and safety of teicoplanin and vancomycin in children with
      antineoplastic therapy-associated febrile neutropenia and gram-positive
      bacteremia.
AB  - To compare their efficacy and safety, teicoplanin and vancomycin were randomly
      administered to 32 children for 52 gram-positive bacteremias during malignancy
      associated neutropenia (<1000/microl). Patients mainly suffered from
      hematological malignancies. Twenty-five episodes were treated with teicoplanin
      (10 mg x kg(-1) x d(-1)) and 21 with vancomycin (40 mg x kg(-1) x d(-1)) plus
      ceftazidime and netilmicin. Six episodes were treated with teicoplanin because of
      previous "red man" reaction to vancomycin. Staphylococci (12% Staphylococcus
      aureus) were isolated from 50 episodes and viridans streptococci from 2.
      Defervescence on 3rd-4th day occurred in 29/31 (93.5%) teicoplanin-treated and
      18/21 (85.7%) vancomycin-treated episodes. All 12 teicoplanin-treated and 13/13
      vancomycin-treated episodes with repeat blood cultures on 3rd-4th day showed
      microbiological response. Two teicoplanin-treated and 3 vancomycin-treated
      patients required antifungals. Mild renal insufficiency appeared in 5 vancomycin
      treated patients that was corrected without drug discontinuation. While both
      glycopeptides exhibit equal clinical and microbiological efficacy, teicoplanin is
      less likely to induce allergic reactions or nephrotoxicity in children.

PMID- 10949985
TI  - Hepatotoxicity of camptothecin derivatives in a primary culture system of rat
      hepatocytes.
AB  - The topoisomerase I inhibitors are a new class of antineoplastic agents currently
      under clinical development. Among these compounds there are some camptothecin
      (CPT) derivatives with improved toxicity profiles and antitumor activity:
      irinotecan (CPT-11) and topotecan (TPT), particularly active against colon, lung
      and ovarian cancer. The aim of this study was to evaluate the cytotoxicity of
      CPT, CPT-11, its metabolite SN38 and TPT in a primary culture system of rat
      hepatocytes. Cytotoxicity was evaluated by measuring the leakage of lactate
      dehydrogenase (LDH) into the medium and by assessing cell viability in terms of
      tetrazolium salts (MTT) reduction by mitochondrial dehydrogenase activity. Our
      results showed that cytotoxicity was limited in the case of short drug exposure.
      There was a significant and time-dependent increase in LDH leakage and a
      significant time- and dose-dependent decrease in MTT reduction after 3 h of
      incubation (p<0.01). In the treatments with doses related to peak plasma levels,
      CPT-11 was less responsible for the observed in vitro hepatotoxicity than its
      metabolite SN38; TPT had lower LDH leakage compared to SN38 and CPT-11 but showed
      significant and early (3 h) decrease in MTT reduction: this may mean a different
      mechanism of cellular damage. These results demonstrate that CPT derivatives are
      directly toxic to liver cells in a distinct time- and dose-related response.

PMID- 10949986
TI  - Potential transmission of the cytogenetic effects of cisplatin in the male
      germline cells of Swiss mice.
AB  - Cisplatin (CP) (in Oncoplatin), a widely used drug in cancer chemotherapy, and
      cyclophosphamide (CY) (in Endoxan), another anticancer drug, were investigated as
      the test chemical and positive control, respectively, for their cytogenetic
      effects on spermatogonia of mice at 24 hours post-treatment after a single
      exposure. The different doses of the chemicals tested were CP 2, 3, 5 mg/kg and
      CY 40 mg/kg b.w. of mice. Each of the doses of CP induced a significant number of
      chromosomal aberrations, mostly chromatid breaks and fragments. The potential
      transmission of such cytogenetic effects of the chemicals from spermatogonia to
      spermatocytes was assessed at week 4 post-treatment from the primary
      spermatocytes, which showed a significant number of aberrant spermatocytes with
      atypical bivalents viz. spermatocytes with autosomal and/or XY univalents,
      tetravalents and with extra elements. The probable causes of the formation of
      univalents and tetravalents are discussed. The transmission of the cytogenetic
      effects of the chemicals from spermatogonia up to sperm was assessed at week 8
      post-treatment from the morphology of sperm collected from vas. Quantitatively
      the transmission of such effects was found decreased substantially by the time
      the exposed spermatogonia became sperm. Still there was the occurrence of a few
      abnormal sperm at week 8 post-treatment. The probable causes of the quantitative
      decrease in the transmission of the effects from spermtogonia to sperm are
      discussed.

PMID- 10949987
TI  - A pilot study of low dose hydroxyurea as a novel resistance modulator in
      metastatic renal cell cancer.
AB  - Mechanisms of chemoresistance in renal cell carcinoma include P-glycoprotein,
      overexpression of multidrug resistance-1 (mdr1) gene, and unstable chromosomal
      aberrations. In vitro exposure of resistant tumor cells to low dose hydroxyurea
      causes loss of chromosomal aberrations, decrease in the mdr1 gene copies, and
      increased sensitivity to vinblastine. Patients received continuous hydroxyurea
      500 mg every Monday, Wednesday and Friday. Vinblastine 5 mg/m2 was given
      intravenously on days 1 and 8 every 21 days. Seventeen patients with a median age
      of 63 (range 40-80) received a median of 3 courses of vinblastine (range 1-14).
      Toxicities included: > or = grade 3 non-hematologic toxicity (1) and febrile
      neutropenia (2). No treatment related mortality occurred. Three patients (17.6%)
      had partial responses. The median survival was 38.0 weeks (95% CI = 26.9-49.1
      weeks). The addition of hydroxyurea given at the dose of 500 mg orally three
      times weekly had no major impact on the expected antitumor effect of vinblastine.

PMID- 10949988
TI  - High efficacy of paclitaxel and doxorubicin as first-line therapy in advanced
      breast cancer: a phase I-II study.
AB  - The aim of this study was to define the maximum tolerated dose (MTD) of
      paclitaxel (TAX) in combination with doxorubicin (ADM). To evaluate the efficacy
      and tolerability of this combination, TAX was administered in escalating doses of
      30 mg/m2, starting from 120 mg/m2, by 1 hour continuous infusion, per group of
      three patients; ADM was administered at a fixed dose of 50 mg/m2, 24 hours before
      administering TAX (phase 1). The combination was recycled every 3 weeks. In phase
      II, TAX was administered at the MTD defined in phase I. Thirty-six women were
      enrolled. The MTD of TAX was 220 mg/m2. Objective responses were observed in
      28/34 (82%) assessable patients. The median progression-free survival was 11.8
      months and overall survival 27.8 months. The main clinical toxicity was
      neutropenia (grade III-IV) of short duration (94%). Two patients developed
      cardiac toxicity. The combination TAX+ADM is very effective in advanced breast
      cancer.

PMID- 10949989
TI  - Zymogen granule fragility as a parameter for ascertaining the functional state of
      pancreatic acinar cells in vitro.

PMID- 10949990
TI  - Utility of gender determination in cell line identity.

PMID- 10949991
TI  - Expression of recombinant erythropoietin in stably transformed Drosophila
      melanogaster S2 cells.

PMID- 10949992
TI  - Establishment and characterization of a caprine mammary myoepithelial cell line
      (CMMyoEC).

PMID- 10949993
TI  - Characterization of four novel epithelial ovarian cancer cell lines.

PMID- 10949994
TI  - Culture in the rotating-wall vessel affects recombinant protein production
      capability of two insect cell lines in different manners.
AB  - The production of recombinant secreted alkaline phosphatase protein in virally
      infected insect cells was studied in shaker flask and high aspect rotating-wall
      vessel (HARV) culture. Two commonly used cell lines, Spodoptera frugiperda Sf-9
      (Sf-9) and a nonaggregating isolate of the Trichoplusia ni BTI-Tn-5B1-4 (Tn-5B1
      4) cell line, Trichoplusia ni Tn-5B1-4-NA (Tn-5B1-4-NA), were used and monitored
      for 120-h postinfection. Different responses to culture in the HARV were seen in
      the two cell lines. While the Sf-9 cell line was able to produce slightly greater
      amounts of recombinant protein in the HARV than in shaker flask controls, the Tn
      5B1-4-NA cell line produced significantly lesser amounts in the HARV than in the
      shaker flasks. Both cell lines exhibited longer life spans and longer periods of
      protein production in HARV culture than in shaker flask culture, presumably due
      to lower levels of shear encountered in the HARV. The important difference was in
      the protein production rate responses of the two cell lines. While the protein
      production rates of Sf-9 cells were comparable in both HARV and shaker flask
      cultures, the protein production rates of Tn-5B1-4-NA cells were much lower in
      HARV culture than in shaker flask cultures. The conclusion is drawn that cell
      line-specific adaptation to the HARV strongly influences recombinant protein
      production.

PMID- 10949995
TI  - Microgravity culture reduces apoptosis and increases the differentiation of a
      human colorectal carcinoma cell line.
AB  - Our hypothesis is that rotation increases apoptosis in standard tissue culture
      medium at shear stresses of greater than approximately 0.3 dyn/cm2. Human MIP-101
      poorly differentiated colorectal carcinoma cells were cultured for 6 d in
      complete medium in monolayers, on Teflon-coated nonadherent surfaces (static
      three-dimensional [3D]) or in rotating 3D cultures either in microgravity in low
      earth orbit (3D microg) or in unit gravity on the ground (3D 1g). Apoptosis
      (determined morphologically), proliferation (by MIB1 staining), and the
      expression of epidermal growth-factor receptor (EGF-R), TGF-alpha, or TGF-beta
      were assessed by immunohistochemistry, while the expression of the
      differentiation marker carcinoembryonic antigen (CEA) was assessed on Western
      blots. Over the course of 6 d, static 3D cultures displayed the highest rates of
      proliferation and lowest apoptosis. This was associated with high EGF-R, TGF
      alpha, and TGF-beta expression which was greater than that of a monolayer
      culture. Both rotated 3D lg and 3D microg cultures displayed lower expression of
      EGF-R, TGF-alpha, or TGF-beta and proliferation than that of monolayer or static
      3D cultures. However, rotated 3D microg displayed significantly less apoptosis
      and greater CEA expression than rotated 3D 1g cultures. When rotated cultures of
      MIP-101 cells were grown uncler static conditions for another 3 d, proliferation
      increased and apoptosis decreased. Thus, rotation appears to increase apoptosis
      and decrease proliferation, whereas static 3D cultures in either unit or
      microgravity have less apoptosis, and reduced rotation in microgravity increases
      CEA expression.

PMID- 10949996
TI  - Generation of an immortal differentiated lung type-II epithelial cell line from
      the adult H-2K(b)tsA58 transgenic mouse.
AB  - This paper describes a new fully differentiated Type-II alveolar epithelial cell
      line designated T7, derived from transgenic H-2K(b)-tsA58 mice, capable of being
      passaged as an immortalized cloned cell line in culture. H-2K(b)-tsA58 mice
      harbor a temperature-sensitive (ts) mutant of the simian virus 40 (SV40) large
      tumor antigen (T antigen) under the control of the gamma-interferon (INF)
      inducible mouse major histocompatibility complex H-2Kb promoter. When cultured
      under permissive conditions (33 degrees C and in the presence of gamma-INF) cells
      isolated from H-2Kb-tsA58 mice express the large T antigen, which drives the
      cells to proliferate. However, upon withdrawal of the gamma-INF and transfer of
      the cells to a higher temperature (39 degrees C), T antigen expression is turned
      off, the cells stop proliferating and differentiate. The T7 cell line is a clonal
      cell line originally derived from a Type-II cell-rich fraction isolated from
      lungs of H-2Kb-tsA58 mice. The T7 cells form confluent monolayers, and have a
      polarized epithelial cell morphology with tight junctions and apical microvilli.
      In addition, the T7 cells have distinct cytoplasmic lamellar bodies, which become
      more numerous and pronounced when the cells are grown under nonpermissive
      conditions. The T7 cells synthesize and secrete phosphatidylcholine and the three
      surfactant proteins, SP-A, SP-B, and SP-C. The T7 cell line is unique in that it
      is the first non-tumor-derived Type-II cell line capable of synthesizing and
      secreting the major components of surfactant. Based on the criteria studied, the
      T7 cell line is phenotypically very similar to normal Type-II cells. The T7 cell
      line, therefore, should prove a valuable experimental system to advance the study
      of the cell biology/physiology of surfactant metabolism and secretion as well as
      serve as a model for other studies of Type-II cell physiology.

PMID- 10949997
TI  - Differentiation of myoblasts is accelerated in culture in a magnetic field.
AB  - We developed a new cell stimulation method in which magnetic microparticles (MPs)
      were introduced into the cytoplasm of cultured myoblasts and the cells were
      cultured in a magnetic field. The differentiation of myoblasts was examined from
      the viewpoint of their morphology and myogenin production. After exposure to the
      magnetic field, the cells containing MPs became larger and were elongated along
      the axis of the magnetic poles. Myogenin, a muscle-specific regulatory factor
      involved in controlling myogenesis, was formed earlier, and myotubes were seen
      earlier and more frequently in this group of myoblasts than in the other groups
      (cells alone without magnetic field, cells containing MPs but without magnetic
      field, and cells alone with magnetic field). Moreover, we succeeded in
      differentiation of early muscle cells with striated myofibrils in culture at 0.05
      T. The precisely quantitative and stable stimulus induced by a magnetic field
      developed in the present study offers a new approach to elucidate the entire
      process of myoblast differentiation into myotubes.

PMID- 10949998
TI  - Up-regulation of E-cadherin and I-catenin in human hepatocellular carcinoma cell
      lines by sodium butyrate and interferon-alpha.
AB  - Human E-cadherin is a homophilic cell adhesion molecule and its expression is
      well preserved in normal human hepatocytes; a decrease in its expression has been
      observed in poorly differentiated hepatocellular carcinoma cells. We examined the
      alteration of E-cadherin and catenin expressions caused by differentiation
      inducers in human hepatocellular carcinoma cells. Hepatocellular carcinoma cell
      lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA),
      dexamethasone (DEX), sodium butyrate, and interferon-alpha. E-cadherin expression
      was only up-regulated by butyrate and interferon-alpha (IFN-alpha) in both cell
      lines, studied by means of fluorescence immunostaining and flow cytometry. The
      localization of E-cadherin staining was shown at their cell membrane. According
      to the increase in E-cadherin expression, beta-catenin expression appeared at the
      cell membrane of both cell lines when treated with butyrate and IFN-alpha. Such
      an appearance was not observed when cells were treated with ATRA and DEX. Western
      blotting showed that alpha- and y-catenin expression was not changed, while only
      the expression of beta-catenin increased. Beta-catenin oncogenic activation as a
      result of amino acid substitutions or interstitial deletions within or including
      parts of exon 3, which has been demonstrated recently, was not detected in these
      cell lines by direct deoxyribonucleic acid sequencing. These results suggest that
      the expression and interaction between E-cadherin and wild-type beta-catenin are
      potentially modulated by butyrate and IFN-alpha, and that these two agents are
      potent inhibitors of hepatocellular carcinoma cell invasion and metastasis.

PMID- 10949999
TI  - Infection of cultured embryo cells of the pacific oyster, Crassostrea gigas, by
      pantropic retroviral vectors.
AB  - The inability to stably introduce and express foreign genes has hampered basic
      research in molluscan species. We cultured cells from dissociated embryos of the
      Pacific oyster, Crassostrea gigas, and infected these primary cultures with
      pantropic retroviral vectors containing the envelope glycoprotein of vesicular
      stomatitis virus. Luciferase transgene expression mediated by different
      heterologous promoters was demonstrated for at least 9 d after infection of the
      cells. Surprisingly, the promoter reproducibly mediating the highest level of
      luciferase expression was the retroviral promoter (U3 region of long terminal
      repeat) from the Moloney murine leukemia virus. The infection efficiency using a
      low multiplicity of infection (0.05) was estimated by quantitative polymerase
      chain reaction to be between 0.1-0.5%. This system will facilitate studies of
      gene expression and regulation and should be widely applicable to other molluscan
      species.

PMID- 10950001
TI  - Practice parameters for the prevention of venous thromboembolism. The Standards
      Task Force of the American Society of Colon and Rectal Surgeons.

PMID- 10950000
TI  - Establishment and characterization of an Ostrinia nubilalis cell line, and its
      response to ecdysone agonists.
AB  - A cell line derived from embryonic tissues of the European corn borer, Ostrinia
      nubilalis (UMC-OnE), was established in EX-CELL 401 medium containing 10% fetal
      bovine serum. The cells grew in suspension, and were mainly spherical in shape.
      The cell doubling times at the 17th and 79th passages were 56 and 36 h,
      respectively. DNA amplification fingerprinting showed that the DNA profile of the
      OnE cell line was different from that of the southwestern corn borer, Diatraea
      grandiosella (UMC-DgE), and that of the cotton bollworm, Helicoverpa zea (BCIRL
      HZ-AM1). The OnE cell line was responsive to treatments of 20-hydroxyecdysone and
      the ecdysone agonists, methoxyfenozide (RH-2485) and tebufenozide (RH-5992).
      These compounds caused similar effects on the cells, which included cell clumping
      and decreased cell proliferation. The clumps were observed on the third day of
      incubation, and became larger after 7 d of incubation. After 168 h of incubation,
      methoxyfenozide and tebufenozide were 35 and 11 times more effective,
      respectively, in inhibiting proliferation of the OnE cells than was 20
      hydroxyecdysone.

PMID- 10950002
TI  - Internal sphincterotomy is superior to topical nitroglycerin in the treatment of
      chronic anal fissure: results of a randomized, controlled trial by the Canadian
      Colorectal Surgical Trials Group.
AB  - PURPOSE: This was a multicenter, randomized, controlled trial to compare the
      effectiveness of topical nitroglycerin with internal sphincterotomy in the
      treatment of chronic anal fissure. METHODS: Patients with symptomatic chronic
      anal fissures were randomly assigned to 0.25 percent nitroglycerin tid or
      internal sphincterotomy. Both groups received stool softeners and fiber
      supplements and were assessed at six weeks and six months. RESULTS: Ninety
      patients were accrued, but 8 were excluded from the analysis because they refused
      internal sphincterotomy after randomization (6), the fissure healed before
      surgery (1), or a fissure was not observed at surgery (1). There were 38 patients
      in the internal sphincterotomy group (22 males; mean age, 40.3 years) and 44
      patients in the nitroglycerin group (15 males; mean age, 38.7 years). At six
      weeks 34 patients (89.5 percent) in the internal sphincterotomy group compared
      with 13 patients (29.5 percent) in the nitroglycerin group had complete healing
      of the fissure (P = 5x10(-8)). Five of the 13 patients in the nitroglycerin group
      relapsed, whereas none in the internal sphincterotomy group did. At six months
      fissures in 35 (92.1 percent) patients in the internal sphincterotomy group
      compared with 12 (27.2 percent) patients in the nitroglycerin group had healed (P
      = 3x10(-9)). One (2.6 percent) patient in the internal sphincterotomy group
      required further surgery for a superficial fistula compared with 20 (45.4
      percent) patients in the nitroglycerin group who required an internal
      sphincterotomy (P = 9x10(-6)). Eleven (28.9 percent) patients in the internal
      sphincterotomy group developed side effects compared with 37 (84 percent)
      patients in the nitroglycerin group (P<0.0001). Nine (20.5 percent) patients
      discontinued the nitroglycerin because of headaches (8) or a severe syncopal
      attack (1). CONCLUSIONS: Internal sphincterotomy is superior to topical
      nitroglycerin 0.25 percent in the treatment of chronic anal fissure, with a high
      rate of healing, few side effects, and low risk of early incontinence. Thus,
      internal sphincterotomy remains the treatment of choice for chronic anal fissure.

PMID- 10950003
TI  - Randomized, controlled trial of topical phenylephrine for fecal incontinence in
      patients after ileoanal pouch construction.
AB  - INTRODUCTION: Fecal incontinence is experienced by some patients with an ileoanal
      reservoir pouch. The alpha1-adrenergic agonist phenylephrine raises resting anal
      sphincter pressure in healthy volunteers and may be of value in these patients.
      METHODS: Twelve patients (7 female), median age 44 (range, 29-67) years were
      studied. All had fecal incontinence despite a noninflamed pouch of normal size
      and ultrasonographically structurally normal anal sphincter muscles. Patients
      were treated with topical 10 percent phenylephrine and placebo gels, allocated in
      random order in a double-blind, crossover study for two four-week periods. Before
      and during treatment, maximum resting anal sphincter pressure and anodermal blood
      flow were measured, a symptom questionnaire was completed, and incontinence score
      was determined using a validated scale. RESULTS: Six of 12 (50 percent) patients
      improved subjectively after phenylephrine compared with one on placebo (P =
      0.07). Four patients had complete cessation of incontinence with active
      treatment. Phenylephrine significantly reduced the incontinence score (P =
      0.015). It also resulted in a significant rise in mean maximum resting anal
      sphincter pressure when compared with placebo (P = 0.012). For all 12 patients,
      mean percent subjective improvement was higher after phenylephrine compared with
      placebo (P = 0.04). There were no side effects. CONCLUSIONS: Topical
      phenylephrine significantly improves fecal continence in patients with an
      ileoanal pouch. In some patients it totally eliminates nocturnal episodes. The
      mechanism of benefit is likely to be one of altered neural sphincter control.
      This is the first study of the use of a topical pharmacologic agent to treat
      fecal incontinence and may have a wider application.

PMID- 10950004
TI  - Is local excision adequate therapy for early rectal cancer?
AB  - PURPOSE: Radical surgery of rectal cancer is associated with significant
      morbidity, and some patients with low-lying lesions must accept a permanent
      colostomy. Several studies have suggested satisfactory tumor control after local
      excision of early rectal cancer. The purpose of this study was to compare
      recurrence and survival rates after treating early rectal cancers with local
      excision and radical surgery. METHODS: One hundred eight patients with T1 and T2
      rectal adenocarcinomas treated by transanal excision were compared with 153
      patients with T1N0 and T2N0 rectal adenocarcinomas treated with radical surgery.
      Neither group received adjuvant chemoradiation. Mean follow-up time was 4.4 years
      after local excision and 4.8 years after radical surgery. RESULTS: The estimated
      five-year local recurrence rate was 28 percent (18 percent for T1 tumors and 47
      percent for T2 tumors) after local excision and 4 percent (none for T1 tumors and
      6 percent for T2 tumors) after radical surgery. Overall recurrence was also
      higher after local excision (21 percent for T1 tumors and 47 percent for T2
      tumors) than after radical surgery (9 percent for T1 tumors and 16 percent for T2
      tumors). Twenty-four of 27 patients with recurrence after local excision
      underwent salvage surgery. The estimated five-year overall survival rate was 69
      percent after local excision (72 percent for T1 tumors and 65 percent after T2
      tumors) and 82 percent after radical surgery (80 percent for T1 tumors and 81
      percent for T2 tumors). Differences in survival rate between local excision and
      radical surgery were statistically significant in patients with T2 tumors.
      CONCLUSIONS: Local excision of early rectal cancer carries a high risk of local
      recurrence. Salvage surgery is possible in most patients with local recurrence,
      but may be effective only in patients with T1 tumors. When compared with radical
      surgery, local excision may compromise overall survival in patients with T2
      rectal cancers.

PMID- 10950005
TI  - Usefulness of endorectal ultrasound after preoperative radiotherapy in rectal
      cancer: comparison between sonographic and histopathologic changes.
AB  - PURPOSE: Our aim was to assess the advantages of endorectal ultrasound after
      preoperative radiotherapy in rectal cancer, its reliability in tumoral staging,
      and its capacity to identify completely sterilized lesions. METHODS: From 1994 to
      1997, 29 patients with rectal cancer were systematically subjected to endorectal
      ultrasound before and after preoperative radiotherapy. Each patient was
      administered 30 to 50 Gy, followed by surgery six to eight weeks after completion
      of radiotherapy. Endorectal ultrasound was performed using a biplanar (linear and
      sectorial) endorectal probe. The morphologic, quantitative, and echo-pattern
      changes of the irradiated tumor were examined. Results of ultrasound findings
      before and after radiotherapy and a histologic examination of the surgical
      specimens were compared. Histopathologic studies were used to evaluate
      macromicroscopical radiation-induced changes, case by case. A comparison between
      tumoral shrinkage and fibrotic replacement was made using the semiquantitative
      Dworak's method. RESULTS: Morphologically and quantitatively, postradiation
      endorectal ultrasound showed the reappearance of anatomic cleavage planes, a
      considerable shrinkage of the tumor, and in low rectal tumors, an increase in the
      distance from the anorectal ring in more than 50 percent of the cases. These data
      had a direct influence on surgical treatment. Histologic examination showed that,
      in 28 out of 29 cases, fibrosis was the most dominant component of the irradiated
      lesions, varying by more than 50 to 100 percent of the lesion (four cases pTO). A
      comparison of postradiation endorectal ultrasound with histopathology revealed
      that fibrosis became the morphologic basis of ultrasound images; therefore, after
      radiotherapy, what endorectal ultrasound staged was no longer the tumor but the
      extent of fibrosis in the rectal wall. A histopathologic examination showed that
      the residual tumor, when present, was always within the fibrosis, never outside
      or separate from it. Postradiation endorectal ultrasound showed echo-pattern
      changes. Some of the changes (more echogenic and nonhomogeneous lesions) were
      histologically related to the persistence of the tumor to a considerable degree;
      other changes (reappearance of parietal layers) were related to complete
      sterilization of lesions in two of three cases. CONCLUSIONS: From the morphologic
      and quantitative point of view, postradiation endorectal ultrasound provides
      oncologists and surgeons useful information to assess treatment effectiveness and
      plan the surgical approach. From the tumor staging point of view, our report
      presents a completely new concept: that six to eight weeks after radiotherapy,
      endorectal ultrasound no longer stages the tumor, but rather the fibrosis that
      takes its place. However, postradiation endorectal ultrasound is a valid tool,
      because the extent of fibrosis in the rectal wall is a direct indication of the
      depth of residual cancer. A residual tumor, when present, is always inside the
      fibrosis. Finally, however, as regards the capacity of endorectal ultrasound to
      exclude or indicate complete sterilization of the lesion, the actual significance
      of the echo-pattern changes we observed needs to be assessed further by studies
      on a large number of cases.

PMID- 10950006
TI  - Significance of a normal surveillance colonoscopy in patients with a history of
      adenomatous polyps.
AB  - PURPOSE: The aim of this study was to determine the appropriate surveillance for
      patients with a history of adenomatous polyps whose last colonoscopic examination
      was normal. METHODS: This was a retrospective review of a database of 7,677
      colonoscopies (1990 to 1996). In patients under colonoscopic surveillance, we
      reviewed cases of patients who had received three colonoscopies (an index
      (initial) colonoscopy positive for adenomas and 2 follow-up colonoscopies
      (interim and final)). The risk of adenomas and cancers at final follow-up
      colonoscopy was compared between patients having a normal interim colonoscopy and
      those with a positive interim colonoscopy. The risk at final colonoscopy was also
      stratified by time interval and the size and number of adenomas at the initial
      index colonoscopy. RESULTS: Two hundred four patients undergoing surveillance for
      adenomas met inclusion criteria. At index colonoscopy the median polyp size was 1
      cm and median frequency was three polyps. At all follow-up colonoscopies, we
      detected 493 adenomas and one cancer (median follow-up, 55 months). At 36 months
      patients with a normal interim colonoscopy (n = 91) had significantly fewer
      polyps than patients with a positive interim colonoscopy (n = 113; 15 vs. 40
      percent; P = 0.0001). By 40 months, adenomas were detected in more than 40
      percent of patients in both groups. The risk after a normal interim colonoscopy
      was not affected by time interval or number or size of polyps. Adenomas found
      subsequent to a normal interim colonoscopy were dispersed throughout the colon in
      28 patients and isolated to the rectosigmoid in 6 patients. CONCLUSIONS: In
      patients with a history of adenomas, a normal follow-up colonoscopy is associated
      with a statistically but not clinically significant reduction in the risk of
      subsequent colonic neoplasms. These patients require follow-up surveillance
      colonoscopy at a four-year to five-year interval.

PMID- 10950007
TI  - Synchronous and "early" metachronous colorectal adenocarcinoma: analysis of
      prognosis and current trends.
AB  - PURPOSE: We evaluated the accuracy of preoperative diagnostic examinations and
      determined whether patients with synchronous colorectal cancers differ from
      patients with a single colorectal malignancy in clinicopathologic factors, the
      possibility of early metachronous colorectal cancer, and postoperative outcome.
      METHODS: A retrospective evaluation of 1,780 patients with primary colorectal
      adenocarcinoma from 1987 to 1993 was performed. We divided patients into three
      groups: Group 1, single colorectal adenocarcinoma; Group 2, synchronous
      colorectal adenocarcinoma; and Group 3, early metachronous colorectal
      adenocarcinoma. RESULTS: There were 52 cases (3 percent) in Group 2 and 13 cases
      (1 percent) in Group 3 (<3 years from the index colorectal cancer operation).
      Differences in age, gender, and cancer-free rate among the three groups did not
      reached statistical significance. Compared with cancers in Group 1, significantly
      more proximal tumor locations and early cancer stage were noted for the second
      and third cancers in Group 2. In Group 3 a significantly more proximal tumor site
      was noted for the index colorectal cancer but cancer stage showed no significant
      difference from cancers in Group 1. Better histologic type was also noted in the
      index and second cancers in Group 2 than in cancers in Group 1. There was a
      higher incidence of associated benign adenoma in Group 2 (35 vs. 15 percent in
      Group 1). The positivity rate of Group 2 was significantly higher by preoperative
      colonoscopy (71 percent) and incidental findings at surgery (58 percent) than
      barium enema examination (30 percent). CONCLUSION: Preoperative barium enema
      examination was an unsatisfactory tool for detecting synchronous tumors.
      Preoperative colonoscopy demonstrated a higher positivity rate, but it still
      failed to detect nearly 30 percent of cases with synchronous tumors.
      Intraoperative palpation of the whole colorectum could detect nearly 60 percent
      of unexpected synchronous tumors. We believe both colonoscopy and intraoperative
      palpation of the whole colorectum are crucial to the early detection of
      synchronous colorectal cancer.

PMID- 10950008
TI  - Artificial anal sphincter: prospective clinical and manometric evaluation.
AB  - INTRODUCTION: Artificial anal sphincter has been proposed in severe anal
      incontinence when local treatment is unsuitable or has failed. The outcome after
      implantation of this newly developed device has not yet been determined. METHODS:
      Twenty-four consecutive patients (7 men; median age, 44; standard deviation, 18;
      range, 14-80 years) implanted since May 1996 for a minimum of six months at three
      centers were prospectively evaluated. Continence (scoring system, 0 (normal) to
      120 (complete incontinence)), rectal emptying, and general satisfaction were
      assessed clinically and at anal manometry preoperatively and postoperatively at a
      six-month interval. The causes of incontinence included anal trauma (9 cases),
      neuropathy (6 cases), neurologic disorders (4 cases), congenital malformations (3
      cases), and prolapse (2 cases). Median duration of incontinence was 7.5 (standard
      deviation, 8) years. Stomas pre-existed in two cases and was created at
      implantation in one. RESULTS: Median follow-up was 20 (standard deviation, 8;
      range, 10-35) months. Seven patients had their devices explanted, and
      reimplantation was successfully performed in three of these cases. At the end of
      follow-up, 20 (83 percent) patients had an implanted activated device. Fecal
      incontinence score dropped significantly from a median 106 (standard deviation,
      13) preoperatively to 19 (standard deviation, 32), 25 (standard deviation, 29),
      and 25 (standard deviation, 25) at six months, one year, and the end of follow
      up, respectively (P<0.0001). Minor and major emptying difficulties occurred in
      seven and two patients, respectively. A high degree of satisfaction was achieved
      at the end of follow-up in 18 (75 percent) of the total series. Median anal
      pressures at rest on manometry increased significantly from 28 (standard
      deviation, 17; range, 5-76) mm Hg preoperatively to 60 (standard deviation, 17;
      range, 38-96) mmHg with a closed cuff at the end of follow-up. These pressures
      dropped to 30 (standard deviation, 16; range, 9-65) mm Hg with an open cuff, and
      reocclusion time lasted a median of 4.6 minutes (standard deviation, 3 minutes;
      range, 38 seconds to 10 minutes). CONCLUSION: Artificial anal sphincter provided
      prolonged and reasonably good functional results in severe incontinence,
      reproducing an efficient sphincteric mechanism and allowing satisfactory anal
      occlusion and rectal emptying in approximately 75 percent of cases in this study.
      The definitive explantation rate was kept low by careful patient selection and
      appropriate surgical and perioperative management.

PMID- 10950009
TI  - Electrocautery snare resection stimulates cellular proliferation of residual
      colorectal tumor: an increasing gene expression related to tumor growth.
AB  - PURPOSE: Recently, endoscopic mucosal resection has been performed commonly for
      colorectal tumors. However, incomplete endoscopic mucosal resection produces a
      residual tumor that grows rapidly. The aim of this study was to clarify the
      characteristics of the residual tumor using the nude mouse model. METHODS: Human
      colon cancer cells (colo201 or colo320DM) were implanted subcutaneous into nude
      mice. We then removed more than one-half of the tumor with an electrocautery
      snare or a surgical knife, and compared the tumor growth rate with that of
      control tumors. Before and after resection, we examined the Ki-67 labeling index
      of the tumors with an immunohistochemical assay and mRNA expression for epidermal
      growth factor receptor, vascular endothelial growth factor, and transforming
      growth factor alpha. RESULTS: Residual tumors showed a higher growth rate in
      tumor volume than control tumors using both methods (electrocautery snare and
      surgical knife). Colo201 groups showed a higher total volume change per day than
      colo320DM groups after resection. Furthermore, these tumors also showed a higher
      Ki-7 labeling index, and a stronger epidermal growth factor receptor and
      transforming growth factor alpha mRNA expression than primary and control tumors
      in the colo201 implanted groups. There was no significant difference in vascular
      endothelial growth factor mRNA expression between groups implanted with colo201
      or colo320DM. CONCLUSION: Our results suggest that residual tumors caused by
      incomplete endoscopic mucosal resection may have a higher growth potential than
      the tumors before resection.

PMID- 10950010
TI  - Postoperative intra-abdominal free gas after open colorectal resection.
AB  - PURPOSE: An erect chest radiograph for subdiaphragmatic free gas can be a useful
      adjunct in detecting a defect in gastrointestinal continuity. The usefulness of
      this test after laparotomy has not been defined, because the period of
      persistence of free gas is unknown. We set out to determine the length of time
      for natural absorption of postlaparotomy pneumoperitoneum in a prospective cohort
      study. METHOD: Plain erect chest radiographs were performed on the second and
      fourth postoperative day and daily thereafter until the disappearance of
      subdiaphragmatic free gas after laparotomy. RESULTS: Seventy-five consecutive
      patients were studied after informed consent. The mean age was 62.1 (standard
      error of the mean, 1.7) years. On the fifth postoperative day, sixth
      postoperative day, and seventh postoperative day, 71.6, 80, and 89 percent of
      patients, respectively, had no visible subdiaphragmatic gas. Five patients had
      gas persisting beyond the tenth postoperative day. Two of these patients did not
      have an anastomosis. The use of drainage tubes did not affect significantly the
      mean time to disappearance of subdiaphragmatic free gas (4.5 vs. 4.9 days; P =
      0.45: t-test). The duration of surgery, body mass index, and time to resume bowel
      function had no significant effect on gas disappearance. Two patients had a
      clinical leak on the fifth postoperative day. This was manifested as an increase
      in the collection of subdiaphragmatic gas during the course of a day. CONCLUSION:
      By the sixth postoperative day 80 percent of patients had no subdiaphragmatic
      free gas on an erect chest radiograph regardless of the presence of a drainage
      tube. The erect chest radiograph may therefore be a simple and readily available
      adjunct in the evaluation of postoperative abdominal pain, especially after the
      sixth postoperative day when a similar prior examination is done routinely on the
      fourth postoperative day for comparison.

PMID- 10950011
TI  - Intraobserver and interobserver measurements of the anorectal angle and perineal
      descent in defecography.
AB  - PURPOSE: Anorectal angle and perineal descent can be measured either by drawing a
      line defined by the impression of the puborectalis muscle and the tangential of
      the posterior rectal wall (Method A) or by drawing a straight line at the level
      of the posterior rectal wall parallel to the central longitudinal axis of the
      rectum (Method B). The aim of this study was to assess the reproducibility of
      measuring anorectal angle and perineal descent by two different methods according
      to intraobserver and interobserver measurement and to evaluate which method
      yields more consistent results. METHODS: Five physicians who have had an average
      of 1.3 years (range, 6 months to 1.5 years) experience in defecographic
      measurement drew both lines on 63 randomly selected defecographic films and
      measured anorectal angle and perineal descent by the two methods. The
      defecographic parameters were measured twice by each observer during a three-week
      interval. To avoid potential bias, one physician who did not participate in
      either measurement of perineal descent or anorectal angle performed all data
      collection. Intraobserver and interobserver agreement was quantified using Shrout
      and Fleiss intraclass correlation coefficients. RESULTS: The mean and range of
      intraclass correlation coefficients for intraobserver agreement of measuring
      anorectal angle and perineal descent by Method A were 0.71 (0.6-0.78) and 0.89
      (0.74-0.97), respectively, whereas with Method B the coefficients were 0.81 (0.73
      0.89) and 0.93 (0.89-0.99), respectively. Regarding the interobserver agreement
      of the five observers, the mean coefficients for measurement of both anorectal
      angle and perineal descent by both methods showed similar agreement levels (0.88
      and 0.98 by Method A and 0.89 and 0.97 by Method B). The mean (+/- standard
      deviation) values of anorectal angle and perineal descent found by Method B were
      significantly larger than those found by Method A (103.3 degrees +/- 19.6 and
      6.56+/-3.20 cm and 91.1 degrees +/- 25.6 and 5.64+/-3.42 cm, respectively;
      P<0.001). CONCLUSION: Intraobserver and interobserver intraclass correlation
      coefficients of anorectal angle and perineal descent, which were measured by both
      methods, were more than 0.60, indicating that both methods are reliable and
      consistent for measurement of anorectal angle and perineal descent. However,
      centers should consistently use the same line for measurement of anorectal angle
      and perineal descent because of the statistically significant differences between
      the two methods and the possibility of inconsistent results.

PMID- 10950012
TI  - Iodine absorption after intraoperative bowel irrigation with povidone-iodine.
AB  - PURPOSE: Povidone-iodine is a commonly used intrarectal tumoricidal agent in
      patients undergoing colorectal surgery. The aim of this study was to assess
      systemic absorption of total iodine and its effect on thyroid function after
      intrarectal application. METHODS: Twenty patients with carcinoma of the rectum
      received intraoperative irrigation with either povidone-iodine (Group A; n = 10)
      or physiologic saline (Group B; n = 10). Ten patients with carcinoma of the
      sigmoid colon (group C) were treated the same as Group A. Electrolyte, total
      iodine, triiodothyronine, thyroxine, and thyroid-stimulating hormone values were
      measured in serum preoperatively and before intraoperative irrigation and
      immediately, ten minutes, 1 hour, 6 hours, 24 hours, and two weeks after
      irrigation. RESULTS: No significant changes occurred in serum electrolytes. A
      significant uptake of the total iodine was demonstrated in each group. Total
      iodine levels examined immediately, ten minutes, and one hour after irrigation in
      Group C were significantly higher than those examined in Group B. Maximum values
      were obtained one hour after irrigation in Groups A and B and six hours after
      irrigation in Group C. No significant changes occurred in triiodothyronine,
      thyroxine, and thyroid-stimulating hormone levels among the three groups. The
      decrease in triiodothyronine levels after surgery was demonstrated in each group.
      We noted a decrease after surgery in thyroxine levels for Groups A and B and in
      thyroid-stimulating hormone levels for Group B. Those hormones were not affected
      by the administration of povidone-iodine. CONCLUSION: High serum levels of iodine
      did not cause organ toxicity, suggesting that a single use of intraoperative
      bowel irrigation with povidone-iodine may be performed with practically
      negligible risk.

PMID- 10950013
TI  - Relationship between colorectal cancer glutathione levels and patient survival:
      early results.
AB  - PURPOSE: Elevated glutathione is a cause of resistance to anticancer agents and x
      rays. The purpose of this study was to determine the frequency and clinical
      significance of glutathione elevation in human colorectal cancer. METHODS:
      Glutathione levels were measured in 41 colon cancers, 24 rectal cancers, and
      corresponding normal tissues. The patients were then followed up prospectively
      for tumor recurrence and survival. Survival was analyzed by the Kaplan-Meir
      method and Cox proportional hazards regression. RESULTS: Glutathione levels in
      primary colorectal cancers were significantly higher than in the corresponding
      normal tissues. Elevated glutathione levels had a significant negative effect on
      survival in patients with colorectal cancer, whether based on the mean (P = 0.02)
      or median (P = 0.04) normal tissue levels. A negative effect of glutathione
      levels on survival was apparent in patients with colorectal cancer, whether or
      not they were treated with postoperative therapy. The larger the ratio of tumor
      glutathione to normal tissue glutathione, the poorer the prognosis. When adjusted
      for other covariates, glutathione was still a significant predictor of survival.
      CONCLUSIONS: An elevated tumor glutathione level at the time of diagnosis appears
      to confer a poor prognosis in patients with colorectal cancer. Longer-term study
      using a larger number of patients will be required to confirm these findings.
      Knowledge of tumor glutathione content may help identify patients requiring more
      intensive therapy.

PMID- 10950014
TI  - Risk factors for intra-abdominal sepsis after surgery in Crohn's disease.
AB  - PURPOSE: This study examined risk factors for intra-abdominal sepsis after
      surgery in Crohn's disease. METHODS: We reviewed 343 patients who underwent 1,008
      intestinal anastomoses during 566 operations for primary or recurrent Crohn's
      disease between 1980 and 1997. Possible factors for intra-abdominal sepsis were
      analyzed by both univariate (chi-squared test) and multivariate (multiple
      regression) analyses. RESULTS: Intra-abdominal septic complications, defined as
      anastomotic leak, intra-abdominal abscess, or enterocutaneous fistula, developed
      after 76 operations (13 percent). Intra-abdominal septic complications were
      significantly associated with preoperative low albumin level (< 30 g/l; P =
      0.04), preoperative steroids use (P = 0.03), abscess at the time of laparotomy (P
      = 0.03), and fistula at the time of laparotomy (P = 0.04). The intra-abdominal
      septic complication rate was 50 percent (8/16 operations) in patients with all of
      these four risk factors, 29 percent (10/35 operations) in patients with three
      risk factors, 14 percent (14/98 operations) in patients with two risk factors, 16
      percent (33/209 operations) in patients with only one risk factor, and 5 percent
      (11/208 operations) in patients with none of these risk factors (P<0.0001). The
      following factors did not affect the incidence of septic complications; age,
      duration of symptoms, number of previous bowel resections, site of disease, type
      of operation (resection, strictureplasty, or bypass), covering stoma, and number,
      site, or method (sutured or stapled) of anastomoses. CONCLUSIONS: Preoperative
      low albumin level, steroid use, and the presence of abscess or fistula at the
      time of laparotomy significantly increased the risk of septic complications after
      surgery in Crohn's disease.

PMID- 10950015
TI  - Pilonidal cyst: cause and treatment.
AB  - PURPOSE: The treatment of sacrococcygeal pilonidal cyst, despite being considered
      a well-defined clinical entity and opinion as to its acquired origin being almost
      unanimous, has some controversial aspects. Surgery is the principal method of
      treatment, and several techniques have been proposed. All of them try to reduce
      morbidity, to offer conditions of fast cicatrization, to have a low recurrence
      rate, and to offer cure. This study was undertaken to review the available data
      in the literature about the cause of the disease and to determine the current
      optimal method of treatment, evaluating morbidity, healing, recurrence, and cure.
      METHODS: Data available on the topic of pilonidal cyst in the English-language
      literature were obtained from Index Medicus and MEDLINE and were reviewed and
      analyzed. RESULTS: There is nearly a consensus that pilonidal cyst is acquired,
      hair being the agent that causes the disease. Presently, the most-used surgical
      procedure is excision of the cyst, with open or closed wound for healing.
      However, many authors prefer to use the method of incision and curettage. New
      surgical techniques are being proposed. CONCLUSION: The majority of authors
      conclude that sacrococcygeal pilonidal cyst is an acquired disease, although a
      minority believe it is congenital. Although excision is the method of choice for
      most surgeons, in our experience the incision and curettage procedure is the best
      surgical treatment with regard to morbidity, healing, recurrence, and cure of the
      disease.

PMID- 10950016
TI  - Perineal endometriosis with anal sphincter involvement: report of a case.
AB  - INTRODUCTION: Perineal endometriosis with anal sphincter involvement is an
      infrequent occurrence. Wide excision is the best chance of cure of perineal
      endometriosis but may cause incontinence when the anal sphincter is involved.
      Conversely, narrow excision may result in incomplete removal, with increased
      recurrence rates and need of additional therapy. Wide excision with primary
      sphincteroplasty and narrow excision surgical techniques are reviewed. METHODS:
      One case report of perineal endometriosis with anal sphincter involvement and
      previously reported cases were reviewed. Patients were compared based on type of
      resection (wide or narrow excision) and outcome. RESULTS: Since 1957 there have
      been seven reported cases of perineal endometriosis with anal sphincter
      involvement, with the present authors adding one additional case for a total of
      eight. The mean age was 33 (range, 22-47) years. Surgical treatment included wide
      excision with primary sphincteroplasty (2 cases), narrow excision (4 cases), and
      incomplete excision (1 case). One case spontaneously regressed after a subsequent
      pregnancy. There were two recurrences in the narrow excision group and no
      recurrences in the wide excision group. There were no complications reported for
      any of the procedures. CONCLUSIONS: Although follow-up time was variable and the
      numbers small, wide excision with primary sphincteroplasty for patients with
      perineal endometriosis with anal sphincter involvement seems to be the best
      chance of cure with good functional results. It should be considered particularly
      in younger patients to obviate the need of long-term subsequent hormonal therapy
      or re-excision for symptomatic recurrences. In contrast, patients closer to
      menopause (when endometriosis tends to regress) may be treated optimally by
      narrow excision to avoid the risks of significant anal sphincter resection.

PMID- 10950017
TI  - Anal canal squamous-cell carcinoma in situ, clearly demonstrated by indigo
      carmine dye spraying: report of a case.
AB  - To our knowledge, there has been no report of the use of indigo carmine dye
      spraying for the diagnosis of intraepithelial neoplasia. An asymptomatic 58-year
      old female was referred to our hospital with a diagnosis of squamous-cell
      carcinoma in the anal canal. After indigo carmine dye spraying the margin and
      surface appearance of the lesion could be clearly defined. The lesion was
      completely removed by transanal resection. Final histologic diagnosis was
      squamous-cell carcinoma in situ with koilocytosis. Our case suggests that indigo
      carmine could be useful for the diagnosis of intraepithelia neoplasia.

PMID- 10950018
TI  - Laparoscopic-assisted Hartmann's reversal with the Dexterity Pneumo Sleeve.
AB  - Several laparoscopic techniques of Hartmann reversal have been published. An
      alternative laparoscopic-assisted procedure, essentially aseptic, which uses the
      minilaparotomy for colostomy mobilization to apply the Dexterity Pneumo Sleeve
      device is described. This technique combines the advantages of the minimally
      invasive approach with the direct access of the surgeon's hand to the patient's
      abdomen.

PMID- 10950019
TI  - Simple technique for the intraoperative detection of Crohn's strictures with a
      calibration sphere.
AB  - Several methods have been used to detect and evaluate small-bowel strictures in
      Crohn's disease. We describe a simple technique for the calibration of strictures
      using a 2.5-cm medical plastic sphere. This method provides an aseptic, safe, and
      effective calibration of the entire small bowel.

PMID- 10950020
TI  - Norman Nigro lectureship: local recurrence and survival after excision of the
      rectum for cancer.

PMID- 10950021
TI  - Closed vs. open hemorrhoidectomy: associated sphincterotomy and postoperative
      bleeding.

PMID- 10950022
TI  - The use of flow equation for mathematic integration of anorectal physiology.

PMID- 10950023
TI  - Anal cleansing vs. irritation.

PMID- 10950024
TI  - To stent or not to stent?

PMID- 10950025
TI  - Nonsteroidal anti-inflammatory drugs in patients with inflammatory bowel disease.

PMID- 10950026
TI  - Future directions in the medical treatment of primary sclerosing cholangitis: the
      need for combination drug therapy.

PMID- 10950028
TI  - Gastroesophageal reflux disease in intellectually disabled individuals: how
      often, how serious, how manageable?
AB  - Gastroesophageal reflux disease (GERD) is an important and frequently occurring
      problem among intellectually disabled individuals (IDI). Early suspicion and
      recognition of the presence of GERD in IDI is the cornerstone of adequate
      management of these patients. The prevalence of GERD among institutionalized IDI
      with an IQ < 50 is about 50%, with 70% of these reflux patients having
      endoscopically established reflux esophagitis. In case of symptoms as
      hematemesis, rumination, or dental erosions, there is an increased risk for GERD.
      GERD has also been shown to be associated with cerebral palsy, an IQ < 35,
      scoliosis, and the use of anticonvulsant drugs or benzodiazepines. To establish
      the diagnosis, 24-h pH measurement or endoscopy should be used in all those
      intellectually disabled individuals in whom GERD clinically is suspected. The
      efficacy of proton-pump inhibitors (PPIs) in IDI with GERD is indisputable. In
      IDI, adults as well as children, PPIs are highly effective, independent of the
      severity of esophagitis. Marked improvement of symptoms and quality of life can
      be noticed after medical treatment, thereby decreasing the need for surgery in
      this complicated group of patients.

PMID- 10950027
TI  - Hemodynamic assessment of pharmacological response in the treatment of portal
      hypertension: a need to know.

PMID- 10950029
TI  - Fecal incontinence: a practical approach to evaluation and treatment.
AB  - Fecal incontinence is a common problem and can have a major impact on the quality
      of life of those affected. Various disease processes affecting stool consistency,
      rectal sensitivity, or the anal sphincters can cause fecal incontinence.
      Obstetric trauma is now known to be a major cause of sphincter dysfunction. The
      evaluation of the patient with incontinence helps to determine the choice of
      therapy-medical or surgical. The two most important tests are anorectal
      manometry, which provides information on sphincter pressures, and rectal
      sensation, and anal endosonography, which is currently the test of choice for
      defining the anatomy of the anal sphincters. The choice of therapy depends on the
      etiology of incontinence, the anatomy of the sphincters, and also on the effect
      of incontinence on the quality of life of the patient. Control of diarrhea,
      regardless of the cause, should be attempted first. Biofeedback therapy is
      effective in the majority of patients and is particularly attractive because it
      is safe and well tolerated. Surgery is offered when medical therapy is
      unsuccessful or when the etiology is thought to respond best to surgery, such as
      in postobstetric trauma. Sphincter repair, for treatment of selective sphincter
      defects, is the best surgical option. Neoanal sphincters and implanted artificial
      sphincters are far less attractive because of technical difficulties and low
      success rate.

PMID- 10950030
TI  - Health-related quality of life and severity of symptoms in patients with
      Barrett's esophagus and gastroesophageal reflux disease patients without
      Barrett's esophagus.
AB  - OBJECTIVES: The aims of this study were: 1) to compare the health-related quality
      of life (HRQL) of patients with Barrett's esophagus (BE) to that of patients with
      GERD who did not have BE; 2) to compare HRQL of gastroesophageal reflux disease
      (GERD) patients to that of normative data for the US general population; and 3)
      to examine the impact of GERD symptom frequency and severity on HRQL. METHODS:
      The SF-36 and a validated GERD questionnaire were administered to 107 patients
      with biopsy-proven BE and to 104 patients with GERD but no BE by endoscopy.
      Frequent symptoms were defined as symptoms that occurred at least once weekly.
      Severity of symptoms was rated on a scale from 1 to 4 (mild to very severe).
      RESULTS: In all, 85% of the GERD patients and 82% of BE patients completed the
      questionnaires. There was no difference in the scores of the eight subscales of
      the SF-36 between BE patients and those with GERD but without BE (p > 0.05).
      However, both groups scored below average on all subscales of the SF-36 compared
      to published US norms for an age- and gender-matched group. Using multivariable
      linear regression, the social functioning subscale of the SF-36 correlated with
      the presence of heartburn or acid regurgitation, severity of acid regurgitation,
      frequency of heartburn, frequency of acid regurgitation, and number of
      comorbidities. Similarly, the physical functioning subscale correlated with age,
      frequency of heartburn, and number of comorbidities. The bodily pain subscale
      correlated with the frequency of heartburn and number of comorbidities. The
      bodily pain subscale correlated with the frequency of heartburn and the severity
      of dysphagia, whereas the role emotional subscale correlated with the frequency
      of heartburn and the presence of dysphagia. CONCLUSIONS: Although there were no
      differences in HRQL between BE and GERD patients, both groups scored below
      average on the subscales of the SF-36 compared to normal controls. GERD symptom
      frequency and severity were associated with bodily pain and with impaired social,
      emotional, and physical functioning, suggesting a profound impact on daily
      living.

PMID- 10950031
TI  - Long-term follow-up of Barrett's high-grade dysplasia.
AB  - OBJECTIVE: The management of Barrett's high-grade dysplasia (HGD) remains
      controversial. The aims of this study were to evaluate prospectively the outcome
      of unifocal HGD (uHGD) in patients with Barrett's esophagus, and to determine
      demographic and endoscopic features predictive of progression to multifocal HGD
      (mHGD) and/or adenocarcinoma. METHODS: Consecutive Barrett's patients in whom
      uHGD was found at initial endoscopy or during surveillance underwent
      intensification of medical treatment and repeat endoscopy. The study endpoint was
      progression to mHGD or adenocarcinoma or HGD in conjunction with a dysplasia
      associated lesion or mass (DALM). HGD diagnosis was confirmed by a second,
      blinded pathologist. RESULTS: A total of 15 Barrett's patients with uHGD met
      inclusion criteria and have been prospectively followed for a mean +/- SD of 36.8
      +/- 23.2 months. All were white and male, with a mean age +/- SD of 61.4 +/- 14.9
      yr. Barrett's length varied from 1 to 13 cm (mean, +/- SD, 6.8 +/- 4 cm).
      Overall, eight (53.3%) uHGD progressed: four of 15 (26.7%) to frank cancer
      between 17 and 35 months of follow-up, two of 15 (13.3%) to mHGD with DALM in
      conjunction with one or more foci of possible intramucosal cancer after 12-91
      months of follow-up, one of 15 (6.7%) to mHGD with a focus of possible
      intramucosal cancer after 14 months, and one of 15 (6.7%) to mHGD after 29
      months. Seven of 15 (46.7%) uHGD have regressed, five to no dysplasia and two to
      LGD, over the course of follow-up ranging from 24 to 73 months (mean +/- SD, 43.3
      +/- 19.9). All three patients with short-segment Barrett's esophagus with uHGD
      regressed. Fisher's exact test revealed that Barrett's length > or =3 cm and
      presence of hiatal hernia approached significance (p < 0.08) in predicting uHGD
      progression to mHGD/DALM/cancer. However, use of the log-rank test to account for
      differences in length of follow-up show no significance for hiatal hernia or
      Barrett's length. CONCLUSIONS: Barrett's uHGD has a high risk for progressing to
      mHGD or cancer. Justification of an observational approach to uHGD should be
      discouraged. Markers of uHGD progression, as well as regression, are needed.

PMID- 10950032
TI  - Rabeprazole versus ranitidine for the treatment of erosive gastroesophageal
      reflux disease: a double-blind, randomized clinical trial. Raberprazole Study
      Group.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy and safety of
      the proton pump inhibitor rabeprazole to that of the histamine-2 (H2)-receptor
      antagonist ranitidine in the treatment of erosive gastroesophageal reflux
      disease. The primary indicator of efficacy was the absence of esophageal erosions
      or ulcerations as determined by posttreatment endoscopy. Secondary indicators of
      efficacy included improvement in frequency and severity of daytime and nighttime
      heartburn. METHODS: A total of 338 patients were enrolled and randomly assigned
      to therapy with rabeprazole 20 mg once daily in the morning or to ranitidine 150
      mg four times daily. At baseline and at 4 wk, patients underwent endoscopy for
      evaluation of esophageal lesions. Patients whose lesions healed by wk 4 had
      therapy discontinued; others remained on therapy and had repeat endoscopy at 8
      wk. Also recorded at study visits were patients' ratings of heartburn symptoms
      and overall sense of well being, patients' reports of time lost from daily
      activities, antacid use, and adverse events. Serum gastrin levels were measured
      and argyrophil enterochromaffin-like cell histology evaluated at baseline and
      when the patient ended therapy. RESULTS: At wk 4, healing was observed in 59%
      (98/167) of patients assigned to rabeprazole therapy, compared with 36% (60/169)
      of those receiving ranitidine (p < 0.001). By 8 wk, healing was seen in 87%
      (146/167) and 66% (112/169) of patients in the rabeprazole and ranitidine groups,
      respectively (p < 0.001). There were also significant differences between the two
      groups favoring rabeprazole with respect to resolution or improvement of
      heartburn symptoms and improvement in sense of well-being. No drug-related
      serious adverse events were seen with either therapy; fewer patients assigned to
      rabeprazole had treatment-emergent signs and symptoms. Serum gastrin levels
      increased over baseline in the rabeprazole group, but the mean value remained
      within normal limits. CONCLUSIONS: Rabeprazole was superior to ranitidine in
      esophageal healing and symptom relief in patients with erosive gastroesophageal
      reflux disease, and was equally well tolerated.

PMID- 10950033
TI  - The association between Helicobacter pylori infection and functional dyspepsia in
      patients with irritable bowel syndrome.
AB  - OBJECTIVE: Irritable bowel syndrome (IBS) is associated with an exaggerated
      response to a variety of physiological and nonphysiological gastrointestinal
      stimuli. Many patients with IBS also have functional dyspepsia. Our aim was to
      examine the hypothesis that Helicobacter pylori (H. pylori) infection may
      predispose IBS patients to functional dyspepsia. METHODS: In 69 IBS patients,
      dyspeptic symptoms, H. pylori status, and sociodemographic and psychological
      variables (perceived stress, trait anxiety, and depression) were assessed.
      Sociodemographic and psychological variables were also evaluated in 52 control
      subjects. RESULTS: Mean scores for perceived stress (17.1 +/- 6.0 vs 14.9 +/-
      6.0, p = 0.05), trait anxiety (45.6 +/- 9.1 vs 41.1 +/- 7.8, p = 0.004) and
      depression (9.9 +/- 8.4 vs 5.0 +/- 5.5, p = 0.0002) were higher in IBS patients
      than in controls. In all, 33 of the 69 patients (47.8%) had H. pylori infection,
      and this was associated with relevant symptoms of epigastric pain (odds ratio
      [OR] = 6.77, 95% confidence interval [CI] 1.89-24.3) and postprandial upper
      abdominal fullness (OR = 4.23, 95% CI 1.38-13.2). H. pylori infection and female
      gender were independent predictors of the presence of relevant dyspepsia (OR =
      8.31, 95% CI 2.35-29.5 and 6.06, 95% CI 1.71-21.5, respectively). Symptom
      intensity was associated with the level of perceived stress (total relevant
      symptom number > or =3 vs <3, OR = 1.16 per point on a 40-point perceived stress
      scale, 95% CI 1.01-1.34). CONCLUSIONS: In IBS patients, the presence of dyspepsia
      is associated with H. pylori infection, female gender, and perceived stress.

PMID- 10950035
TI  - A survey of internal medicine residents' knowledge about Helicobacter pylori
      infection.
AB  - OBJECTIVE: Despite recently published national guidelines, many physicians have
      only limited knowledge about Helicobacter pylori infection. We conducted this
      study to assess internal medicine residents' knowledge about H. pylori. METHODS:
      Two hundred and nineteen residents in seven accredited internal medicine training
      programs completed a self-administered questionnaire on personal demographics and
      practices related to testing for-and treating-H. pylori infection. RESULTS: Noon
      conferences (82%), ward teaching (66%), journals (70%), and sponsored symposia
      (27%) were their major sources of H. pylori-related information. Forty-eight
      percent had used office-based tests for the infection. Testing for (and treatment
      of) Helicobacter pylori infection was recommended by 97% (97%) for newly
      diagnosed duodenal ulcer, but by only 61% (63%) for a past history of duodenal
      ulcer. Many recommended testing in unproven conditions and might not have offered
      treatment to an infected patient. A proton pump inhibitor-based triple-drug
      regimen was the treatment of first choice of 55%; 20% recommended proton pump
      inhibitor-based dual regimens. Sixty-six percent and 80%, respectively,
      underestimated the rates of resistance to clarithromycin and metronidazole. In
      the absence of gastrointestinal symptoms, 22% would have ordered Helicobacter
      pylori testing but only 33% of these would undergo treatment if positive.
      CONCLUSIONS: Internal medicine residents usually test for Helicobacter pylori
      infection in appropriate conditions, but may not always treat the infection when
      the result is positive. Most use efficacious treatment regimens although many
      have inaccurate knowledge of resistance rates, which may adversely influence
      prescribing. Education should focus on practical issues surrounding Helicobacter
      pylori testing and treatment such as those contained in the American College of
      Gastroenterology's 1998 practice guidelines.

PMID- 10950034
TI  - Helicobacter pylori and dyspepsia: a population-based study of the organism and
      host.
AB  - OBJECTIVE: The role of Helicobacter pylori (HP) infection in dyspepsia in the
      absence of peptic ulcer remains controversial. Specific attributes of the
      organism or the host response may be important. We aimed to determine whether HP
      infection overall, CagA status, serum gastrin, or serum pepsinogen levels are
      associated with dyspepsia in the community. METHODS: A self-report bowel disease
      questionnaire was mailed to a random sample of Olmsted County, Minnesota
      residents, aged 20-50 yr. All respondents who reported symptoms of dyspepsia or
      irritable bowel syndrome (cases) and all respondents without significant GI
      symptoms (controls) were invited to participate (n = 260). They were each
      assessed by a physician and their medical records reviewed. Serum was obtained to
      measure HP and CagA antibodies, pepsinogen I and II levels, and basal serum
      gastrin using validated assays. RESULTS: Of the 148 (57%) subjects who agreed to
      participate, 36 had dyspepsia (17 had ulcer-like dyspepsia), 35 had irritable
      bowel syndrome (IBS) without dyspepsia, and 77 were asymptomatic. The proportion
      who were seropositive for HP were 17% in dyspepsia (24% in ulcer-like dyspepsia),
      20% in IBS, and 12% in asymptomatic controls. HP was not associated with
      dyspepsia, ulcer-like dyspepsia, or IBS after adjusting for age. Pepsinogen
      levels and serum gastrin were not associated with any of the conditions studied.
      However, CagA antibody positivity was associated with IBS (p < 0.05), and a
      borderline statistically significant association with dyspepsia was detected (p =
      0.08). CONCLUSIONS: In this community, HP infection overall does not seem to
      explain dyspepsia, although the role of CagA-positive HP strains deserve further
      study.

PMID- 10950036
TI  - Are self-expanding metal mesh stents useful in the treatment of benign esophageal
      stenoses and fistulas? An experience of four cases.
AB  - OBJECTIVE: The aim of this study was to review the long-term results of treating
      benign esophageal fistula and stenosis using self-expanding metal stents.
      METHODS: We treated four patients using covered mesh or coiled stents. We removed
      the stents electively in two patients (one endoscopically and one during planned
      partial esophagectomy) and unexpectedly in one patient who developed bleeding.
      One stent migrated and required laparotomy for removal. RESULTS: Placement of
      self-expanding metal stents successfully sealed the benign fistula in two
      patients and reestablished swallowing in two other patients with complicated
      achalasia. Two patients were swallowing normally on long-term follow-up, one died
      of the underlying disease, and one required gastrostomy. CONCLUSION: Temporary
      use of self-expanding metal stents as a feasible option for treating benign
      esophageal stenosis and fistula in patients who have failed other conventional
      treatments.

PMID- 10950037
TI  - Role of endoscopic ultrasound and magnetic resonance imaging in the preoperative
      staging of pancreatic adenocarcinoma.
AB  - OBJECTIVE: Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) have
      both been assessed individually as staging modalities for pancreatic cancer. The
      aim of our study was to assess whether tumor staging by both EUS and MRI in the
      same cohort of patients could predict resectability and unresectability in
      patients with pancreatic cancer. METHODS: A review of 63 patients evaluated
      preoperatively with both EUS and MRI for pancreatic adenocarcinoma between
      January 1995 and December 1998 was done. Patients were staged as resectable or
      unresectable by predefined criteria. Preoperative staging by both modalities was
      compared to surgical outcome and the sensitivity and predictive values of each
      modality for determining resectability and unresectability was determined.
      RESULTS: EUS did not allow for complete T- and N-staging in 10 patients;
      therefore, for EUS, the final analysis was done on 63 of 73 patients (86%). EUS
      correctly staged 22 of 36 patients with resectable tumors. The sensitivity of EUS
      for resectability was 61%, with a positive predictive value of 69%. All 73
      patients had complete MRI examinations; therefore, the final analysis was done on
      all 73 patients. MRI correctly staged 30 of 41 patients with resectable tumors.
      The sensitivity of MRI for predicting resectability was 73% with a positive
      predictive value of 77%. MRI and EUS both predicted resectability in 18 patients,
      of whom 16 (89%) were found to be resectable on surgical exploration. MRI and EUS
      both predicted unresectability in 17 (27%) patients, of whom 4 (24%) were found
      to be resectable on surgical exploration. When both MRI and EUS agreed on
      resectability, the positive predictive value for resectability was 89%. When both
      MRI and EUS agreed on unresectability, the positive predictive value for
      unresectability was 76%. CONCLUSIONS: Neither MRI nor EUS alone were highly
      sensitive or predictive of resectability. However, when both tests agreed on
      resectability, nearly all patients were found to be resectable on surgical
      exploration.

PMID- 10950038
TI  - A comparison of the efficacy and tolerance of pancrelipase and placebo in the
      treatment of steatorrhea in cystic fibrosis patients with clinical exocrine
      pancreatic insufficiency.
AB  - OBJECTIVE: The safety and efficacy of Minimicrospheres, which are enteric-coated,
      delayed-release pancrelipase capsules, on fat absorption in pediatric/adolescent
      and adult cystic fibrosis (CF) patients was assessed. Exocrine pancreatic
      insufficiency, common in CF patients, causes steatorrhea due to insufficient
      release of pancreatic enzymes. METHODS: In the open-label phase, 97 CF patients
      with pancreatic insufficiency and steatorrhea were stabilized on a high-fat diet
      and administered pancrelipase. Seventy-four patients with >80% coefficient of fat
      absorption received placebo or pancrelipase in the double-blind phase. Fat intake
      and excretion, stool frequency and consistency, and clinical global improvement
      were recorded. RESULTS: Average daily fat intake was comparable between treatment
      groups within each age group (adults vs pediatric/adolescent), but placebo
      patients had a significant (p < 0.001) mean decrease in coefficient of fat
      absorption (adult, 36.9 percentage points; pediatric/adolescent, 34.9 percentage
      points) from open-label to double-blind treatment compared to pancrelipase
      patients (adult, 2 percentage points; pediatric/adolescent, 3.25 percentage
      points); this difference was caused by a greater (p < or = 0.001) increase in
      mean fecal fat excretion (grams per day) in the placebo groups compared to
      pancrelipase groups (adult: 61.9 vs 2.3; pediatric/adolescent: 45.4 vs 4.1).
      Change in mean stool frequency from open-label to double-blind phases was
      significantly different (p < or = 0.002) between treatment groups, with increases
      in placebo groups and no difference (adult) or decrease (pediatric/adolescent) in
      pancrelipase groups. Pancrelipase patients' stool consistency remained about the
      same from open-label to double-blind. Placebo patients' stool consistency
      decreased (became softer) from open-label pancrelipase to double-blind placebo.
      Clinical global improvement data showed that > or =83% of pancrelipase patients
      improved or remained unchanged. CONCLUSIONS: Enteric-coated, delayed-release
      (Minimicrospheres) pancrelipase capsules are an effective treatment for
      steatorrhea associated with pancreatic insufficiency in patients with cystic
      fibrosis.

PMID- 10950039
TI  - Ki-ras codon 12 point and P53 mutations: a molecular examination of the main
      tumor, liver, portal vein, peripheral arterial blood and para-aortic lymph node
      in pancreatic cancer.
AB  - OBJECTIVE: Frequent P53 mutations and Ki-ras codon 12 point mutations have been
      reported in pancreatic cancer. Pancreatic cancer often recurs in the liver and/or
      lymph nodes shortly after a surgical resection. The purpose of this study is to
      elucidate the occurrence of microcirculating cancer cells and micrometastasis in
      pancreatic cancer. METHODS: P53 mutations and Ki-ras codon 12 point mutations
      were examined in the main tumor, liver, portal vein, and peripheral arterial
      blood, and para-aortic lymph nodes of patients with pancreatic cancer using
      molecular examinations. RESULTS: P53 mutations in the main tumor were present in
      nine (29%) of 31 patients with pancreatic cancer, whereas a Ki-ras codon 12 point
      mutation was evident in 18 (62%) of 29 examined patients. The peripheral arterial
      and portal vein blood and liver were positive for gene abnormalities in one (5%)
      of 21, in none (0%) of 19, and in one (1%) of 20, respectively. A P53 mutation in
      the main tumor was evident in none (0%) of seven stage I or II carcinomas and in
      nine (38%) of 24 stage III or IV cases, whereas a Ki-ras codon 12 point mutation
      was present in four (67%) of six stage I or II cases and in 14 (61%) of 23 stage
      III or IV cases. In addition, 15 (71%) of 21 patients with gene abnormalities (Ki
      ras codon 12 point and/or p53 mutation) in the main tumor showed lymph node
      metastasis at surgery, whereas five (42%) of 12 without gene abnormalities did
      not demonstrate lymph node metastasis. Two (29%) of six patients with gene
      abnormalities in the main tumor and without metastatic disease at surgery
      developed liver metastasis within 6 months after surgery, whereas all five (100%)
      without the gene abnormalities and metastatic disease at surgery did not develop
      the metastasis, with the sensitivity being 100%, specificity 44%, the predictive
      value of the positive test 36%, and the predictive value of the negative test
      100%. Two patients who had gene abnormalities in the para-aortic lymph node were
      free from histopathological metastasis and these two patients developed para
      aortic lymph node metastasis within 6 months after surgery. CONCLUSIONS: A
      molecular examination of Ki-ras codon 12 and p53 mutations therefore enables us
      to predict, to some degree, the occurrence of liver and lymph node metastasis in
      pancreatic carcinoma.

PMID- 10950040
TI  - Tolerance of nonsteroidal antiinflammatory drugs in patients with inflammatory
      bowel disease.
AB  - OBJECTIVE: We sought to examine whether use of nonsteroidal antiinflammatory
      drugs (NSAIDs) in an outpatient inflammatory bowel disease (IBD) population is
      associated with an increased likelihood of active disease. METHODS: We reviewed
      records of initial outpatient visits of IBD patients to the principal author from
      June 1995 to December 1997, with regard to use of aspirin and other NSAIDs and
      disease activity. RESULTS: Of 40 Crohn's patients seen with active disease, three
      (7.5%) were using NSAIDs; 14 of 72 (19.4%) Crohn's patients seen with inactive
      disease were using NSAIDs. Fifty-eight ulcerative colitis patients were seen with
      active disease, with eight (13.7%) using NSAIDs. Among 21 UC patients initially
      seen while in remission, five (23.8%) were using NSAIDs. CONCLUSIONS: Among this
      group of outpatients, NSAID use was not associated with a higher likelihood of
      active IBD. NSAID use in IBD deserves further study before recommending that
      patients refrain from their use under all circumstances.

PMID- 10950041
TI  - Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a
      case-control study.
AB  - OBJECTIVE: The aim of this study was to determine whether a relationship exists
      between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and exacerbation
      or onset of inflammatory bowel disease (IBD). METHODS: Sixty consecutive IBD
      patients admitted to the hospital were carefully interviewed to ascertain whether
      they used NSAIDs and the relationship in time and duration to the exacerbation
      (or onset) of the IBD; 62 patients with irritable bowel syndrome were similarly
      interviewed and served as controls. RESULTS: In 31% of our IBD population there
      was a correlation between use of NSAIDs and IBD activity, whereas in only 2% of
      the irritable bowel syndrome population who used NSAIDs did this relationship
      exist. CONCLUSIONS: NSAIDs provoke disease activity in both ulcerative colitis
      and Crohn's disease and should be avoided in patients with a history of IBD
      whenever possible.

PMID- 10950042
TI  - Annual cost of care for Crohn's disease: a payor perspective.
AB  - OBJECTIVE: The aim of this study was to estimate the annual cost of care of
      patients with Crohn's disease according to treatment setting. METHODS: Using a
      1994 integrated claims database, patients with a Crohn's-related medical claim
      (ICD-9 code 555) from 10/01/94 to 09/30/95 were included in this analysis. These
      patients were stratified into three mutually exclusive disease severity groups:
      group 1, required hospitalization for Crohn's; group 2, required chronic
      glucocorticoid or immunosuppressive drug therapy for >6 months; group 3, all
      remaining patients. Direct charges (based on reimbursement) and utilization of
      resources were reported for each group. RESULTS: Six-hundred-seven patients were
      analyzed: 117(19%) in group 1, 31(5%) in group 2, and 459(76%) in group 3.
      Average age of all patients was 48 years and 43% of these patients were men.
      Average annual charges for all patients totaled $12,417. Group I patients
      experienced the highest mean charges ($37,135), whereas patients in groups 2 and
      3 incurred $10,033 and $6,277. Approximately 25% of patients accounted for 80% of
      the total charges. CONCLUSIONS: Crohn's disease is associated with high cost.
      Although a minority of Crohn's patients required hospitalization, they tended to
      have higher utilization and were responsible for a majority of total
      expenditures. New therapies have the potential to reduce overall cost of care, if
      they prevent Crohn's-related hospitalizations.

PMID- 10950043
TI  - A prospective randomized placebo-controlled double-blinded pilot study of
      misoprostol rectal suppositories in the prevention of acute and chronic radiation
      proctitis symptoms in prostate cancer patients.
AB  - OBJECTIVE: Radiation proctitis is a known complication of radiation therapy for
      prostate cancer. Available medical treatment is usually ineffective and has
      focused on relieving symptoms after damage has occurred. Our study aimed at
      evaluating the use of misoprostol rectal suppositories in the prevention of acute
      as well as chronic radiation proctitis symptoms. METHODS: A prospective,
      randomized, placebo-controlled, double-blinded trial was conducted in patients
      with recently diagnosed stages B and C prostate cancer who underwent external
      beam irradiation. Patients received either a misoprostol or a placebo suppository
      1 h before each radiation session. Misoprostol suppositories were made from two
      200-microg tablets (Cytotec, Searle Pharmaceuticals, Skokie, IL), whereas the
      placebo was made from cocoa butter. A 12-point radiation proctitis symptom score
      was obtained from each patient at 4, 8, 12, and 36 wk after radiation therapy.
      RESULTS: A total of 16 patients were enrolled. Seven patients received placebo,
      and nine patients received misoprostol. Mean radiation proctitis symptom scores
      in the placebo group were 4.86, 5.86, 5.71, and 3.83 at 4, 8, 12, and 36 wk,
      respectively. The mean scores in the misoprostol group were 0.78, 0.67, 0.33, and
      0.37 at 4, 8, 12, and 36 wk, respectively. The difference between the two groups
      was statistically significant (p < 0.05) at 4, 8, 12, and 36 wk. CONCLUSION:
      Misoprostol rectal suppositories significantly reduce acute and chronic radiation
      proctitis symptoms in patients receiving radiation therapy for prostate cancer.

PMID- 10950044
TI  - Microaggregate of immunostained macrophages in noninflamed gastroduodenal mucosa:
      a new useful histological marker for differentiating Crohn's colitis from
      ulcerative colitis.
AB  - OBJECTIVE: In 10% of cases it may be difficult to differentiate Crohn's colitis
      from ulcerative colitis. Distinguishing the two conditions is important because
      they are distinct entities with different therapeutic implications. Noncaseating
      granulomas are usually considered diagnostic of Crohn's disease. We previously
      reported that the presence of a microaggregate of immunostained macrophages
      within the noninflamed gastroduodenal mucosa was a characteristic finding of
      Crohn's disease. The aim of this study was to determine whether a microaggregate
      of immunostained macrophages can be a reliable marker for differentiating Crohn's
      colitis from ulcerative colitis. METHODS: We investigated the presence of
      microaggregates of immunostained macrophages and epithelioid cell granulomas in
      biopsy specimens taken from the noninflamed gastroduodenal mucosa of 22 known
      Crohn's colitis patients and 23 established ulcerative colitis patients. The
      incidence of microaggregates and granulomas was compared between these two
      groups. RESULTS: Microaggregates and granulomas were detected only in the Crohn's
      colitis patients. In addition, the presence of microaggregates was more frequent
      than that of granulomas in Crohn's colitis patients (54.5% and 18.2%,
      respectively, 95% confidence interval for the difference: 10.0-62.7%).
      CONCLUSION: Detecting a microaggregate of immunostained macrophages in a biopsy
      specimen taken from noninflamed gastroduodenal mucosa seems to be a useful method
      for differentiating Crohn's colitis from ulcerative colitis.

PMID- 10950045
TI  - High prevalence of celiac sprue-like HLA-DQ genes and enteropathy in patients
      with the microscopic colitis syndrome.
AB  - OBJECTIVE: Celiac sprue is associated with specific HLA-DQ genes (mainly DQ2).
      Because there are epidemiological and histopathological similarities between
      celiac sprue and microscopic colitis, we hypothesized that these syndrome may
      share an HLA genetic predisposition and pathogenesis. METHODS: The HLA-DQ genes
      of 25 patients with celiac sprue, 53 patients with the microscopic colitis
      syndrome, and 429 normal controls were typed and compared. Serum was analyzed for
      antigliadin and antiendomysial antibodies. Small intestinal biopsies were
      analyzed for signs of histopathology. RESULTS: HLA-DQ2 or DQ1,3 (the latter as
      DQ1,7,DQ1,8, or DQ1,9) were seen more frequently in both patient groups relative
      to controls. In patients with the microscopic colitis syndrome, serological tests
      for celiac sprue were weakly positive in 17%; mild inflammation of the small
      intestine without villous atrophy was present in 43%, and inflammation plus
      partial or subtotal villous atrophy was present in 27%. CONCLUSIONS: A shared set
      of predisposing HLA-DQ genes account for the epidemiological overlap of celiac
      sprue and microscopic colitis. Mild to moderate mononuclear cell inflammation of
      the small intestine, often accompanied by partial or subtotal villous atrophy, is
      frequent in patients with the microscopic colitis syndrome. Although further
      studies will be necessary to determine if this enteropathy is induced by dietary
      gluten, we speculate that the small intestinal but not colonic histopathology in
      patients with microscopic colitis is caused by immunological gluten sensitivity.

PMID- 10950046
TI  - Indium-111 leukocyte scintigraphy in suspected bowel ischemia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the utility of indium-111
      leukocyte (In-111 WBC) scintigraphy in a large number of patients with suspected
      bowel ischemia. METHODS: All patients who underwent In-111 WBC scintigraphy for
      possible bowel ischemia over a 4-yr period and had subsequent endoscopic or
      surgical biopsy were retrospectively evaluated. Early (1-4 h postinjection) and
      late (18-24 h postinjection) images were obtained. Any study with tracer activity
      in the bowel on early or late images was considered positive for bowel ischemia.
      RESULTS: Fifty-nine patients were included in the analysis. In-111 WBC
      scintigraphy detected 23 of 24 cases of bowel ischemia (sensitivity = 96%). Of 35
      cases without ischemia, 16 had a negative In-111 WBC scintiscan (specificity =
      46%). Negative and positive predictive values for the diagnosis of bowel ischemia
      were 94% and 55%, respectively. Of the 19 cases without bowel ischemia and a
      positive scintiscan, 15 had another intraabdominal process responsible for the
      patients' symptomatology. CONCLUSIONS: In-111 WBC scintigraphy is a highly
      sensitive diagnostic tool for bowel ischemia. A normal In-111 WBC scintiscan
      strongly suggests that this disease is not present.

PMID- 10950047
TI  - Colonic inflammation found at diagnosis of juvenile retention polyps in pediatric
      patients.
AB  - OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile
      retention polyp (JRP) may have prognostic value. However, the significance of
      abnormal mucosal histology with JRP has not been evaluated. We evaluated the
      significance of mucosal histology at the time of JRP removal with respect to
      future development of inflammatory bowel disease (IBD) and polyp recurrence.
      METHODS: The medical records of patients who had an endoscopic polypectomy
      performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through
      4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified
      in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%)
      had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis,
      14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients
      had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation
      elsewhere in the colon; however, biopsies around the polyp site were not
      obtained. One patient with inflammation did not have the location of the polyp
      documented. Four patients (16.7%) had IBD at the time of polypectomy; two were
      diagnosed prior and two coincident with JRP. None have subsequently been
      diagnosed with IBD. There was no difference in polyp recurrence between those
      with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up
      period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience,
      histological mucosal inflammation is a common finding with JRP. This inflammation
      may be a precursor for the development of JRP but has no predictive value for
      polyp recurrence. This colitis does not seem to be associated with IBD.

PMID- 10950048
TI  - Higher expression of glucocorticoid receptor in peripheral mononuclear cells in
      inflammatory bowel disease.
AB  - OBJECTIVE: Glucocorticoids are widely used in the treatment of inflammatory bowel
      disease (IBD). Up- and down-regulated expression of glucocorticoid receptors (GR)
      has been reported for different chronic inflammatory diseases. The aim of this
      study was to investigate the expression of GR and their apparent dissociation
      constant (Kd) in patients with IBD. METHODS: Thirty-nine patients with IBD (22
      with ulcerative colitis, 17 with Crohn's disease) and 35 normal controls were
      studied. Twenty-five patients did not receive steroids, 14 patients were treated
      with steroids. Peripheral blood mononuclear cells from patients and controls were
      isolated using the Ficoll-Hypaque gradient and a whole cell [3H]-dexamethasone
      binding assay and Scatchard plot analysis were performed to assess GR number and
      the apparent dissociation constant. Results were expressed as mean +/- standard
      deviation. RESULTS: Normal controls showed an expression of 3,969 +/- 1,555 GR
      per cell with an apparent dissociation constant of 6.16 +/- 3.8 nmol/L. IBD
      patients without steroids had a significant increase both in the expression of GR
      per cell (6,401 +/- 2,344; p < 0.0001; Wilcoxon-Mann-Whitney test) and in the
      apparent dissociation constant (11.02 +/- 7.57 nmol/L; p = 0.006). Expression of
      GR in IBD patients was suppressed to normal levels under steroid treatment (4,594
      +/- 2,237; p = 0.024), but Kd remained elevated (13.56 +/- 9.05 nmol/L). Plasma
      cortisol levels were not different between IBD patients and the control group.
      CONCLUSIONS: Our data show a systemic increase in GR expression and a decrease in
      the affinity to the GR in IBD, in contrast to other inflammatory diseases such as
      rheumatoid arthritis and asthma. These changes point towards a systemic character
      of IBD, which might be considered in a decision between topical and systemic
      treatment.

PMID- 10950049
TI  - Factors predictive of response to cyclosporin treatment for severe, steroid
      resistant ulcerative colitis.
AB  - OBJECTIVE: Cyclosporin-A (CSA) has been demonstrated to be effective for
      treatment of severe, steroid-resistant ulcerative colitis (UC). Use of CSA has
      been limited, however, because of low 1-yr response rates and the potential for
      complications. The aim of this study is to define clinical and laboratory factors
      predictive of response in severe, steroid-resistant UC. METHODS: A retrospective
      review of 36 cases of severe, steroid-resistant UC treated with CSA was
      performed. Intravenous (i.v.) CSA was administered at an initial dose of 2.5
      mg/kg, and oral (p.o.) CSA was given as twice the i.v. dose. Clinical response
      was recorded and logistic regression analysis was performed on clinical and
      laboratory factors for prediction of response to CSA. RESULTS: Of 36 patients, 25
      responded to i.v. CSA and were switched to p.o. CSA. Of the 25, 13 required
      colectomy by 9 months. The other 12 patients had a sustained response to CSA and
      avoided colectomy at 9 months. Overall, 24 of 36 patients treated with CSA
      required colectomy by 9 months. A high percentage of band neutrophils (bands) on
      admission was found to be a significant predictor of response to CSA.
      CONCLUSIONS: Bands on admission are predictive of response to CSA and ultimately,
      the requirement for surgery in steroid-resistant UC.

PMID- 10950050
TI  - Detection of autoantibodies against tissue transglutaminase in patients with
      celiac disease and dermatitis herpetiformis.
AB  - OBJECTIVE: Endomysial autoantibodies (EmA) are specific for celiac disease. The
      target antigen has been identified as tissue tranglutaminase (tTG). Our aim was
      to study the accuracy of a newly developed enzyme-linked immunosorbent assay
      (ELISA) for easy detection of tTG autoantibodies. METHODS: Thirty-one sera from
      patients with histologically proven celiac disease and 23 healthy controls were
      examined for EmA using monkey esophagus and human umbilical cord as substrate.
      IgA-tTG autoantibodies were determined by newly developed ELISA. Additionally,
      sera from patients with dermatitis herpetiformis (n = 20), inflammatory bowel
      disease (IBD; n = 32), chronic liver disease (n = 36), and diabetes mellitus (n =
      19) were tested. RESULTS: The sensitivity of the tTG autoantibody ELISA accounted
      for 90% detection in patients with untreated celiac disease. The specificity was
      76% owing to positive values in the lower range in patients with IBD (15%),
      chronic liver disease (36%), and diabetes (22%), all of whom were negative for
      EmA. In dermatitis herpetiformis patients 90% were EmA-positive. Of these, only
      47% showed elevated tTG autoantibodies. Preincubation of sera from dermatitis
      patients with tTG abolished immunofluorescent staining of endomysial structures.
      CONCLUSION: Detection of mid- to high-titer tTG autoantibodies is highly specific
      for celiac disease. However, in the low-titer range, overlap exists with liver
      disease, IBD, and diabetes. Tissue transglutaminase autoantibodies may evolve as
      a new screening and follow-up method for celiac disease. Although tTG seems to be
      a major autoantigen in dermatitis herpetiformis, the low sensitivity of both tTG
      ELISA and immunofluorescence using human umbilical cord suggests differential
      involvement of tTG in this disease.

PMID- 10950051
TI  - Budesonide or prednisone in combination with ursodeoxycholic acid in primary
      sclerosing cholangitis: a randomized double-blind pilot study. Belgian-Dutch PSC
      Study Group.
AB  - OBJECTIVE: PSC has characteristics of an (auto)immune-mediated disease: however,
      few studies have evaluated corticosteroid therapy for this disorder. METHODS: We
      performed an 8-wk double-blind randomized pilot study to assess the effects of
      additional treatment with 9 mg budesonide (n = 6) versus 3 mg budesonide (n = 6)
      versus 10 mg prednisone (n = 6) in patients who had been treated with UDCA (mean
      dose, 12 mg/kg/day) for at least 5 months without achieving biochemical
      remission. Pruritus and fatigue were evaluated using visual analog scales. Serum
      liver biochemistry was measured every 4 wk. At entry and at the end of the trial,
      adrenocorticotrophic hormone (ACTH) and dehydroepiandrosterone (DHEA) were
      measured to assess effects on the pituitary-adrenal axis. Duodenal bile was
      collected for assessment of biliary corticosteroid activity. RESULTS: Pruritus
      decreased significantly more in the prednisone group compared to both the 3-mg
      and the 9-mg budesonide groups (p < 0.05). Alkaline phosphatase (mean: -23.4%; p
      = 0.03) and IgG (mean: -16.2%; p = 0.04) decreased in the prednisone group,
      whereas bilirubin, gamma-glutamyl transferase, aspartate aminotransferase, and
      alanine aminotransferase did not change significantly. No significant clinical or
      liver biochemical changes were observed in the 3-mg and 9-mg budesonide groups.
      Significantly larger drops in serum ACTH were found in the 10-mg prednisone group
      (-40.7%; p = 0.04) and 9-mg budesonide group (-36.6%; p = 0.02) compared to the 3
      mg budesonide group (+ 19.0%). No significant differences in percentage change in
      baseline values for DHEA between the three treatment arms were found. Mononuclear
      cell proliferation assays did not demonstrate corticosteroid activity in bile.
      Autoimmune hepatitis was observed in one case (9 mg budesonide) when
      corticosteroids were tapered off. CONCLUSION: The results of this pilot study
      suggest only minor beneficial short-term effects of prednisone but not budesonide
      on symptoms and serum liver tests in UDCA-treated PSC patients.

PMID- 10950053
TI  - The prognostic significance of subclinical hepatic encephalopathy.
AB  - OBJECTIVE: Subclinical hepatic encephalopathy may have prognostic significance
      with regard to the development of clinical hepatic encephalopathy and survival.
      METHODS: We studied 116 consecutive patients with histologically proven cirrhosis
      of the liver for subclinical hepatic encephalopathy, using Number Connection Test
      A, Digit Symbol Test, and spectral analysis of the electroencephalogram. RESULTS:
      Twenty-five patients (22%) were diagnosed as having subclinical hepatic
      encephalopathy. Patients with subclinical hepatic encephalopathy were older, had
      a higher Child-Pugh score, and more often had esophageal or gastric varices and
      episode(s) of clinical hepatic encephalopathy in their history. During a median
      follow-up of 29 months (range, 1-49 months), patients with subclinical hepatic
      encephalopathy significantly more often had episodes of clinical hepatic
      encephalopathy; survival, however, was similar to that of patients without
      subclinical hepatic encephalopathy, and was determined mainly by the Child-Pugh
      score. The Child-Pugh score was also superior to subclinical hepatic
      encephalopathy in predicting episodes of clinical hepatic encephalopathy.
      CONCLUSIONS: The prognostic significance of subclinical hepatic encephalopathy
      appears limited.

PMID- 10950052
TI  - Propranolol in primary and secondary prophylaxis of variceal bleeding among
      cirrhotics in India: a hemodynamic evaluation.
AB  - OBJECTIVE: In the present study, we attempted to complete the hemodynamic
      assessment of propranolol response in cirrhotics with esophageal varices at high
      risk of bleeding, in one sitting, so as to identify nonresponders at the
      earliest. Some noninvasive indicators of this response were also evaluated.
      METHODS: Hepatic venous pressure gradient (HVPG) was measured in 33 such cases
      (18 nonbleeders, 15 bleeders) before and 90 min after an oral dose of 80 mg
      propranolol, and reduction by > or =20% taken as responder. RESULTS: Twenty-two
      patients (66.67%) responded (HVPG reduction > or =26%), whereas 11 (33.33%) did
      not (HVPG reduction < or =6%). Postdrug HVPG between responders and nonresponders
      showed a significant difference (p < 0.001). Neither baseline HVPG (p > 0.1),
      baseline CI (p = 0.665), nor baseline stroke volume index (p > 0.1) could predict
      responder status. Difference of HVPG reduction (percent) between bleeders (21.49
      +/- 35.53) and nonbleeders (40.58 +/- 23.95) approached, but did not reach,
      statistical significance (p = 0.076). However, logistic regression showed this
      difference to be significant (p = 0.026). Age of responders was found to be
      significantly lower than that of nonresponders (p approximately equals 0.05).
      During a follow-up of 9-38 months, only one of 22 responders (on propranolol) had
      an episode of variceal bleed. None in whom HVPG fell to < or = 12 mm Hg bled.
      CONCLUSION: The study suggests that single-sitting hemodynamic assessment of
      acute response to high-dose oral propranolol clearly differentiates between
      responders and nonresponders. Moreover, it appears that prior history of variceal
      bleeding and old age negatively influences the effect of propranolol.

PMID- 10950054
TI  - Humoral immune response to hepatitis C after liver transplantation: assessment of
      a new recombinant immunoblot assay.
AB  - OBJECTIVE: The immune control of infection with hepatitis C virus (HCV) is poorly
      understood; vigorous antibody responses to viral proteins seem to coexist with
      the virus and thus whether they are neutralizing remains controversial. HCV
      related liver failure is the leading indication for orthotopic liver
      transplantation (OLT) worldwide. Attenuated antibody responses in
      immunosuppressed patients and decreased reliability compared to assessment of HCV
      RNA has hampered the use of antibody testing post-OLT. The goals of this current
      analysis were twofold: to determine the sensitivity of a prototype strip
      immunoblot assay (RIBA 3.0, Chiron Diagnostics) for the diagnosis of HCV post
      OLT; to determine if there was a correlation between antibody response and
      severity of histological recurrence. METHODS: The study was comprised of 76 HCV
      positive individuals divided into three patient groups: liver allograft
      recipients with evidence of mild or no histological recurrence (n = 52), liver
      allograft recipients with evidence of severe HCV recurrence and allograft
      cirrhosis (n = 12), and nontransplant patients being enrolled in an induction
      interferon trial (n = 12). All transplant patients had histological follow-up of
      at least 1 yr. RESULTS: Sixty of the 64 (94%) HCV-positive OLT recipients had 1+
      reactivity to two or more recombinant antigens; three of the patients who lacked
      a detectable response had minimal histological recurrence and one had severe
      recurrence. All nontransplant patients demonstrated 4+ reactivity to at least two
      antigens, and 55/64 (86%) OLT recipients demonstrated this same level of
      reactivity. Seven of the nine patients lacking this high level of reactivity had
      evidence of minimal recurrence. Furthermore, the mean (+/- SEM) level of antibody
      reactivity for c100 (p = 0.04) and NS5 (p = 0.01) were significantly lower for
      patients with mild recurrence after OLT, compared to the other groups. The level
      of antibody reactivity was unrelated to HCV genotype or viral load. CONCLUSIONS:
      The recently developed RIBA 3.0 assay for detection of antibodies to HCV appears
      to be highly sensitive for the diagnosis of HCV post-OLT. In general, the level
      of antibody reactivity was comparable in the transplant patients and in
      nonimmunosuppressed controls. The pathogenic implications of the relatively
      diminished humoral response in patients with mild recurrence post-OLT are
      discussed.

PMID- 10950055
TI  - Significance of soluble TNF receptor-I in acute-type fulminant hepatitis.
AB  - OBJECTIVE: Fulminant hepatitis is associated with apoptosis of hepatocytes, which
      is mediated via Fas and tumor necrosis factor (TNF) receptors. The clinical
      significance of apoptotic factors and these receptors was investigated in
      fulminant hepatitis. METHODS: Serum levels of TNF-alpha, soluble TNF receptor-I
      and -II, soluble Fas antigen, and Fas ligand were measured. Then, the
      relationships between these parameters and the severity or prognosis of fulminant
      hepatitis were studied. RESULTS: Serum levels of TNF-alpha, soluble TNF receptor
      I, and soluble TNF receptor-II were increased in acute-type fulminant hepatitis.
      In particular, soluble TNF receptor-I was significantly higher than in patients
      with subacute-type fulminant hepatitis, severe acute hepatitis, acute hepatitis,
      or healthy controls. The soluble TNF receptor-I level continued to increase or
      remained high in patients who died of acute-type fulminant hepatitis, and eight
      of nine patients had a level >10 ng/ml. In contrast, the soluble TNF receptor-I
      level remained <10 ng/ml in survivors. Soluble Fas and soluble Fas ligand levels
      tended to increase in all types of acute liver disease and were not specific to
      fulminant hepatitis. CONCLUSION: Our findings suggested that monitoring the
      soluble TNF receptor-I level may help to assess the prognosis of acute-type
      fulminant hepatitis and that TNF might be associated with massive hepatic
      necrosis.

PMID- 10950056
TI  - Significance of Fas antigen-mediated apoptosis in human fulminant hepatic
      failure.
AB  - OBJECTIVE: The aim of this study was to elucidate the role of apoptosis in human
      fulminant hepatic failure. We studied the expression of Fas antigen on liver
      tissues, Fas ligand in lymphocytes, and soluble Fas ligand in patients' serum.
      METHODS: On finding apoptotic cells in fulminant hepatic failure liver, we first
      examined them using the TUNEL method. Subsequently, the expression of Fas was
      studied by immunostaining. Simultaneously, Fas ligand presenting on both liver
      infiltrated cells and peripheral lymphocytes was studied by reverse transcription
      polymerase chain reaction, and soluble Fas ligand in sera was measured by ELISA.
      RESULTS: By using the TUNEL method, we first demonstrated that many apoptotic
      cells existed in fulminant hepatic failure but not in normal ones. Our
      immunohistochemistry study showed that many hepatocytes in fulminant hepatic
      failure strongly expressed Fas. In addition, Fas ligand on both liver
      infiltrating lymphocytes and peripheral lymphocytes in fulminant hepatic failure
      patients was detected. The serum level of soluble Fas ligand was significantly
      increased in fulminant hepatic failure (mean value, 2.91 ng/ml in fulminant
      hepatic failure [n = 10], 1.62 ng/ml in acute hepatitis [n = 10], and 0.27 ng/ml
      in healthy controls [n = 10]). Furthermore, this serum level of sFas ligand was
      significantly associated with prothrombin time both in acute hepatitis and
      fulminant hepatic failure. CONCLUSIONS: The present results indicate that Fas
      mediated apoptosis may be one of the triggers for the induction of fulminant
      hepatic failure.

PMID- 10950058
TI  - Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are
      associated with recurrent or chronic idiopathic pancreatitis.
AB  - OBJECTIVE: We investigated whether mutations of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene and cationic trypsinogen gene are associated
      with recurrent acute, or chronic idiopathic pancreatitis. METHODS: Twenty
      patients with idiopathic pancreatitis (11 women, nine men; mean age, 30 yr) were
      studied for the presence of a CFTR mutation by screening the genomic DNA for more
      than 30 mutations and variants in the CFTR gene. Selected mutations of the
      cationic trypsinogen gene were screened by Afl III restriction digestion or by a
      mutation-specific polymerase chain reaction (PCR). In each patient exons 1, 2,
      and 3 of the cationic trypsinogen gene were sequenced. Patients with a CFTR
      mutation underwent evaluation of further functional electrophysiological test
      (intestinal current measurement). RESULTS: No mutation of the cationic
      trypsinogen gene was detected. A CFTR mutation was detected in 6/20 (30.0%)
      patients. Three patients (15.0%) had a cystic fibrosis (CF) mutation on one
      chromosome (deltaF508, I336K, Y1092X), which is known to cause phenotypical
      severe cystic fibrosis. One patient was heterozygous for the 5T allele. In
      addition, two possibly predisposing CFTR variants (R75Q, 1716G-->A) were detected
      on four patients, one of these being a compound heterozygous for the missense
      mutation I336K and R75Q. No other family member (maternal I336K; paternal R75Q;
      sister I1336K) developed pancreatitis. An intestinal current measurement in
      rectum samples of patients with a CFTR mutation revealed no CF-typical
      constellations. CONCLUSIONS: CFTR mutations are associated with recurrent acute,
      or chronic idiopathic pancreatitis, whereas mutations of the cationic trypsinogen
      mutation do not appear to be a frequent pathogenetic factor.

PMID- 10950057
TI  - Human leukocyte antigen DR markers as predictors of progression to liver
      transplantation in patients with chronic hepatitis C.
AB  - OBJECTIVE: Because many patients with chronic viral hepatitis do not progress to
      end-stage liver disease, it is possible that host factors such as human leukocyte
      antigen (HLA) differences are important. Our aims were to determine HLA marker
      specific rates of progression to liver transplantation among patients with
      chronic hepatitis C; and to determine if polymerase chain reaction (PCR)-based
      HLA DRB1 typing can be performed on stored serum samples. METHODS: Forty-two
      hepatitis C virus RNA-positive liver transplant patients and 87 untransplanted
      patients were included in a Cox proportional hazards model to test whether the
      occurrence of certain HLA DRB1 markers were associated with progression to liver
      transplantation. HLA DRB1 typing was performed on stored serum samples using a
      PCR method. RESULTS: There were no differences among the HLA DRB1 markers with
      regard to the HLA marker-specific rate of progression to transplantation among
      patients with chronic hepatitis C. CONCLUSIONS: HLA DRB1 markers do not appear to
      be associated with progression of disease in chronic viral hepatitis C. It is
      possible to perform PCR-based HLA DRB1 typing on stored frozen serum samples.

PMID- 10950059
TI  - Survey of internal medicine residents' use of the fecal occult blood test and
      their understanding of colorectal cancer screening and surveillance.
AB  - OBJECTIVE: Primary care physicians have imperfect understanding of current
      colorectal cancer screening guidelines and recommendations. Furthermore,
      compliance with colorectal cancer screening by internal medicine residents has
      been demonstrated to be poor. We sought to identify whether current trainees in
      internal medicine had adequate understanding of colorectal cancer screening and
      surveillance and test utilization. METHODS: We applied a structured questionnaire
      about colorectal cancer screening and the use of fecal occult blood tests to 168
      internal medicine residents at four accredited programs in the U.S. They were
      also asked for recommendations about six hypothetical patients who may have been
      candidates for screening or surveillance. RESULTS: Seventy-one percent identified
      50 yr as the currently recommended age to commence screening in an average-risk
      individual; 64.3% would begin screening with fecal occult blood testing and
      flexible sigmoidoscopy and 4.8% with colonoscopy. Most perform fecal occult blood
      testing on stool obtained at digital rectal exam and without prior dietary
      restrictions. Many use fecal occult blood testing for indications other than
      colorectal cancer screening. Only 29% recommended colonoscopy to evaluate a
      positive fecal occult blood test. Most residents plan to be screened for
      colorectal neoplasia at the appropriate age; significantly more opted for
      colonoscopy than recommended it for their patients. CONCLUSIONS: Internal
      medicine residents have many misperceptions regarding colorectal cancer screening
      and the utility of the fecal occult blood test. Educational efforts should be
      directed at internal medicine residents, many of whom plan careers in primary
      care, where most colorectal cancer screening is currently performed.

PMID- 10950060
TI  - A randomized, controlled trial to assess a novel colorectal cancer screening
      strategy: the conversion strategy--a comparison of sequential sigmoidoscopy and
      colonoscopy with immediate conversion from sigmoidoscopy to colonoscopy in
      patients with an abnormal screening sigmoidoscopy.
AB  - OBJECTIVE: Our study was a randomized, controlled trial to assess a novel
      strategy that provides comprehensive colorectal cancer screening in a single
      visit versus traditional sigmoidoscopy and, where appropriate, colonoscopy on a
      subsequent day. METHODS: Consecutive patients referred for screening were
      randomized to control or so-called "conversion" groups. Patients in the control
      group were prepared for sigmoidoscopy with oral phospho-soda. Those with an
      abnormal sigmoidoscopy were scheduled for colonoscopy on a future day after oral
      polyethylene glycol preparation. In the conversion group, patients were prepared
      with oral phosphosoda. Patients with a polyp >5 mm or multiple diminutive polyps
      were converted from sigmoidoscopy to colonoscopy, allowing comprehensive
      screening in a single visit. Clinical outcomes were assessed by postprocedure
      physician and patient questionnaires. RESULTS: Two hundred thirty-five patients
      were randomized (control = 121, conversion = 114). In the control group, 28% had
      an indication for colonoscopy. Three of 33 (9%) with an abnormal sigmoidoscopy
      did not return for colonoscopy. At colonoscopy, 27% had a proximal adenoma. In
      the conversion group, 28% had an abnormal sigmoidoscopy and underwent conversion
      to colonoscopy. Forty-one percent undergoing colonoscopy in the conversion group
      had a proximal adenoma. Physicians reported no differences in preparation or
      procedure difficulty, whereas patients reported no differences in the level of
      comfort or overall satisfaction between groups. When queried regarding
      preferences for future screening, 96% chose the conversion strategy. CONCLUSIONS:
      The conversion strategy led to similar outcomes compared to traditional screening
      while improving compliance with colonoscopy in patients with an abnormal
      sigmoidoscopy.

PMID- 10950062
TI  - Screening for high-grade dysplasia in gastroesophageal reflux disease: is it cost
      effective?
AB  - OBJECTIVE: The present study aimed to assess the cost-effectiveness of endoscopic
      screening in patients with gastroesophageal reflux disease (GERD) to rule out
      high-grade dysplasia of Barrett's esophagus. METHODS: Using an incremental cost
      effectiveness ratio as outcome measure, the cost-effectiveness of endoscopic
      screening was compared to not screening in a decision tree. It was assumed that
      GERD patients at age 60 yr undergo a one-time endoscopy with esophageal biopsies,
      targeting abnormal-appearing epithelium. Positive biopsies with respect to high
      grade dysplasia or early esophageal adenocarcinoma result in esophagectomy.
      Transition rates were estimated from U.S. cancer statistics, as well as published
      data of endoscopic sensitivity, specificity, and surgical outcome. Costs of
      screening and cancer care were estimated from Medicare reimbursement data from
      the perspective of a third-party-payor. RESULTS: Compared with no screening,
      screening endoscopy cost $24,700 per life-year saved. The cost-effectiveness of
      screening is quite sensitive to the prevalence of Barrett's esophagus, high-grade
      dysplasia, and adenocarcinoma, as well as the sensitivity, specificity, and cost
      of screening endoscopy. A small drop in the health-related quality of life
      associated with postsurgical states markedly reduced the effectiveness of
      screening. Simultaneous variations of the prevalence, specificity, and health
      related quality of life can easily change screening endoscopy from a life-saving
      into a life-losing strategy. CONCLUSIONS: Under favorable conditions, general
      screening by endoscopy of all patients with reflux symptoms to prevent death from
      esophageal adenocarcinoma may represent a cost-effective strategy; however, such
      conditions may be difficult to meet.

PMID- 10950061
TI  - Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss
      of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Pancreatic cancer is one of the diseases with the poorest prognosis,
      but the associated genetic alterations are not yet well understood. The genetic
      alterations reported to date in pancreatic cancer include frequent mutations of
      the KRAS, TP53, p16, and SMAD4 genes. Mutation of the TP53 gene was reported to
      be associated with a poor prognosis. In this study, we analyzed the association
      of loss of heterozygosity (LOH) with clinicopathological features to attempt to
      devise effective methods in the future for clinically applying our results to
      diagnosis and treatment. METHODS: A total of 55 tumors from patients with primary
      pancreatic ductal carcinomas (34 men and 21 women, mean average age 63.9 yr) in
      which all the relevant clinical and pathological data were available were
      analyzed. A total of 46 cases were surgically resected, and nine cases were not.
      Tumor cells as well as corresponding normal cells were collected by
      microdissection under a microscope, and DNAs were purified. Allelotype analysis
      was performed by the PCR-based method, and the results were statistically
      analyzed. RESULTS: LOH of > or =30% were observed on chromosome arms 17p (47%,
      17/36), 9p (45%, 14/31), 18q (43%, 15/35), 12q (34%, 10/29), and 6q (30%, 10/33).
      LOH of 12q, 17p, and 18q were significantly associated with a poor prognosis.
      Concordant losses of 6q with 17p and 18q were significantly associated with a
      poor prognosis. Concordant losses of 6q with 17p and of 12q with 18q were also
      found. CONCLUSIONS: Because LOH of 12q, 17p, and 18q are significantly associated
      with a poor prognosis, mutation of the putative tumor suppressor genes on these
      chromosome arms may play significant roles in the disease progression. Concordant
      losses of 6q with 17p and of 12q with 18q suggest that protein products of
      putative tumor suppressor genes on 6q and 12q may function in association with
      TP53 and SMAD4, respectively.

PMID- 10950063
TI  - Hemorrhoid clamp.

PMID- 10950064
TI  - Successful treatment of cap polyposis by avoidance of intraluminal trauma: clues
      to pathogenesis.
AB  - "Cap polyposis" is a rarely-encountered condition in which distinctive
      inflammatory polyps are located from the rectum to the distal descending colon.
      Microscopically, the polyps consist of elongated, tortuous, and distended crypts
      covered by a "cap" of inflammatory granulation tissue. Although the pathogenesis
      is unknown, mucosal prolapse has been postulated to be an important etiological
      factor, given certain clinical and histological similarities. We describe two
      cases of cap polyposis with protein-losing enteropathy. One was treated
      successfully by avoidance of straining at defecation. Another resolved after
      double-barreled transverse colostomy. Both successful treatments support a causal
      link of polyposis to prolapse.

PMID- 10950065
TI  - Liver pseudotumor: a rare manifestation of hepatic granulomata caused by Ascaris
      lumbricoides ova.
AB  - A rare case of hepatic granulomata caused by Ascaris lumbricoides ova is
      reported. The patient presented clinically with hepatic mass simulating
      malignancy, and final diagnosis was performed after surgery, which provided
      enough material for histopathological examination.

PMID- 10950066
TI  - CT-guided treatment of ultrasonically invisible hepatocellular carcinoma.
AB  - New techniques of CT-guided management were introduced to ablate ultrasonically
      invisible hepatocellular carcinomas. In six patients with HCC, a total of six
      nodules (8-30 mm in diameter) were treated under the guidance of CT. These
      lesions were not visualized by sonography but were visualized as Lipiodol spots
      on CT after chemoembolization. Tumor localization was successful in all patients
      without difficulty, using a thin needle or hookwire under the guidance of CT. Two
      patients underwent subsequent hepatic resection and/or microwave coagulation
      therapy (MCT) through a small incision after hookwire placement. Four patients
      received percutaneous MCT (n = 2) or ethanol injection (PEI) (n = 2) at the time
      of localization. The postoperative CT with contrast enhancement indicated that
      tumor ablation was complete in four of the five nodules treated with MCT or PEI.
      However, in one nodule (30 mm in diameter) treated with PEI, tumor ablation was
      not complete. There were no complications. There has been no local tumor
      recurrence 6-46 months after treatment in any of the patients. In conclusion,
      these CT-guided procedures were effective in treating ultrasonically invisible
      hepatocellular carcinomas that otherwise would have remained untreated.

PMID- 10950067
TI  - The pitfall of relying on the abdominal radiograph to determine stent function
      after palliation of malignant colonic obstruction using a self-expanding metal
      stent.
AB  - Acute colonic stent malfunction was diagnosed in an 81-yr-old woman who underwent
      palliation of an obstructing rectosigmoid cancer, because abdominal radiography
      showed retained stool and barium. Surgery was avoided after colonoscopy showed
      that the inspissated barium and stool mixture was coating and not obstructing the
      colon. The barium and stool mixture was washed off using the water jet from a
      heat probe unit.

PMID- 10950068
TI  - Problems in the identification of hereditary nonpolyposis colorectal cancer in
      two families with late development of full-blown clinical spectrum.
AB  - The recognition of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) remains
      difficult despite the most recent advancements of molecular biology and
      technology. We describe two families with early onset of cancer but no suspicion
      of hereditary tumors; during follow-up, both families developed a tumor spectrum
      highly suggestive of HNPCC, thus emphasizing the importance of family history for
      a proper identification of hereditary tumors or cancer aggregation.
      Microsatellite instability was negative in tumors from both families and, as
      expected, no germline mutations of the major DNA mismatch repair genes (MSH2 and
      MLH1) could be detected. Suspicion of the disease at the time of proband's lesion
      might have led to prevention, or early diagnosis, of at least three malignant
      tumors. We conclude that a possible genetic origin should always be suspected in
      individuals with early-onset neoplasms of the large bowel and probably of other
      organs such as the endometrium, small bowel, and urothelium, even when the
      initial pedigree does not show marked aggregation of cancers or vertical
      transmission.

PMID- 10950069
TI  - Congenital bronchoesophageal fistula in the adult: a case report.
AB  - Congenital bronchoesophageal fistula is a rare anomaly that may go undiagnosed
      for many years. There are <200 reported cases in the literature. Patients usually
      present with chronic cough, a history of multiple pneumonias, and, less often,
      hemoptysis. The most sensitive test to diagnose a bronchoesophageal fistula is
      barium esophagogram. Surgical resection is the treatment of choice and is
      definitive in almost all cases. We present the case of a 52-yr-old woman with a
      history of cough and multiple pneumonias who sought medical treatment for
      abdominal pain. We discuss the presentation and the radiographic, endoscopic, and
      surgical findings, along with a review of the literature.

PMID- 10950070
TI  - Colorectal cancer: predicting prognosis for patients and probands using
      immunohistochemistry.

PMID- 10950071
TI  - Colon decompression--do we accomplish what we intend?

PMID- 10950072
TI  - Treatment of severe nausea/vomiting--an evidence-based approach.

PMID- 10950073
TI  - "Congenital" esophageal stenosis, corrugated ringed esophagus, and eosinophilic
      esophagitis.

PMID- 10950074
TI  - Seroepidemiology of Helicobacter pylori and hepatitis A virus.

PMID- 10950075
TI  - Spontaneous bacterial peritonitis and bacteremia in fulminant hepatic failure.

PMID- 10950076
TI  - Re: probiotics and C difficile diarrhea.

PMID- 10950077
TI  - Patient knowledge in inflammatory bowel disease.

PMID- 10950078
TI  - Risk factors in irritable bowel syndrome.

PMID- 10950079
TI  - Risk factor for irritable bowel syndrome: role of food allergies.

PMID- 10950080
TI  - Re: melanoma in the GI tract.

PMID- 10950081
TI  - Helicobacter pylori and gastric cancer.

PMID- 10950082
TI  - Experience and volume: the ingredients for successful therapeutic endoscopic
      outcomes, especially ERCP and postgastrectomy patients.

PMID- 10950083
TI  - Innovative thinking for the improvement of medical systems--"ENDOVIEW for the
      patients".

PMID- 10950085
TI  - A novel device for colonoscopic tube decompression.

PMID- 10950084
TI  - Activation of epidermal growth factor receptor kinase in gastric carcinoma: a
      preliminary study.

PMID- 10950086
TI  - A high anti-HBs response in Turkish students of nursing with inexpensive,
      multidose vial hepatitis B vaccine.

PMID- 10950087
TI  - Rectal syndrome as first presentation of metastatic breast cancer.

PMID- 10950088
TI  - Umbilical hemorrhage from a cutaneous varix treated by transjugular intrahepatic
      portosystemic shunt (TIPS)

PMID- 10950089
TI  - Chronic diarrhea: identifying a new syndrome.

PMID- 10950090
TI  - Didanosine-induced hepatitis.

PMID- 10950091
TI  - "Giant" colon lipoma--to attempt endoscopic resection or not?

PMID- 10950092
TI  - High biotinidase activity in type Ia glycogen storage disease.

PMID- 10950093
TI  - Calcium channel blockers and hepatotoxicity.

PMID- 10950094
TI  - Centenarians and Helicobacter pylori.

PMID- 10950095
TI  - Total proctocolectomy and ileal pouch anal anastomosis to successfully treat a
      patient with collagenous colitis.

PMID- 10950096
TI  - Intestinal nodular lymphoid hyperplasia in a patient with chronic diarrhea and
      recurrent sinopulmonary infections.

PMID- 10950097
TI  - Breast metastasis of primary colon cancer.

PMID- 10950098
TI  - Extraesophageal presentations of gastroesophageal reflux disease: an overview.

PMID- 10950099
TI  - Approach to the patient with unexplained chest pain.

PMID- 10950100
TI  - Gastroesophageal reflux and chronic cough.

PMID- 10950101
TI  - ENT manifestations of gastroesophageal reflux.
AB  - Reflux laryngitis is a common disease and is probably only one of several
      laryngeal manifestations associated with GERD. The hypothesis that GER causes
      laryngeal symptoms and conditions remains to be definitively proved. In many
      patients, the cause of laryngeal symptoms may well be multifactorial, and to
      identify definitively those patients in which GER may be playing a role remains a
      challenge. Documentation of GER using 24-h pH monitoring may assist in
      identifying such patients. Pharyngeal pH probe monitoring, although not without
      limitations, may be the optimal method to evaluate such patients in terms of
      documenting the presence of EPR. A suggested algorithm based on the available
      data in evaluating and treating patients with suspected reflux laryngitis is
      shown in Figure 5. First, rule out other causes of hoarseness and laryngitis. An
      ENT consultation is appropriate for hoarseness present >4 wk. Second, empirically
      treat with PPIs b.i.d. for 2-3 months, as esophageal and pharyngeal pH monitoring
      is costly, not readily available, time consuming, and not sensitive in making the
      diagnosis of GERD related laryngitis. If the patient improves after 2-3 months,
      therapy should be stopped and the patient observed. If symptoms recur,
      reinstitution of the PPI at the lowest possible dose or with use of an H2RA to
      maintain remission should be initiated. Third, if no improvement is noted, the
      patient should undergo 24-h pH monitoring with an esophageal and, if possible, a
      pharyngeal probe if the diagnoses of GERD and EPR are still in question. In
      patients in whom there is a high suspicion for GERD, pH monitoring should be
      performed on PPI therapy to determine whether acid suppression is adequate. A pH
      probe should be placed in the stomach if the question to be answered is whether
      1) the PPI regimen is maintaining a pH of >4, or 2) if the addition of a bedtime
      H2RA maintains nocturnal intragastric pH of >4 (52-56). Patients with a
      completely normal pH study who are on no medications should be referred back to
      the ENT physician for further evaluation, as other risk factors for chronic
      laryngitis such as voice overuse may benefit from concomitant voice therapy. If
      upright reflux is the predominant reflux pattern, increasing the b.i.d. PPI dose
      is reasonable; but if nighttime supine reflux is predominant, recent literature
      suggests that the addition of a bedtime H2RA will suppress nocturnal acid
      breakthrough. There are, however, no long-term studies with the PPI plus H2RA
      regimen that document persistent nocturnal acid suppression and that show
      clinically significant differences in patients with nocturnal acid breakthrough.
      Surgery should be cautiously considered for patients who are unresponsive to PPI
      therapy and who have documented or undocumented evidence of GERD or EPR. The body
      of experience concerning GERD and the extraesophageal manifestations of GERD
      suggests that patients who do not respond to adequate PPI acid suppression will
      do poorly after antireflux surgery.

PMID- 10950102
TI  - Asthma and gastroesophageal reflux.

PMID- 10950103
TI  - Dental erosion: predominant oral lesion in gastroesophageal reflux disease.

PMID- 10950105
TI  - Early detection cancer research network.

PMID- 10950104
TI  - Overview of therapy for the extraesophageal manifestations of gastroesophageal
      reflux disease.

PMID- 10950106
TI  - Response of nasopharyngeal carcinoma cells to Epstein-Barr virus infection in
      vitro.
AB  - Many nasopharyngeal carcinoma (NPC) biopsy specimens contain Epstein-Barr virus
      (EBV). However, the response of NPC cells to EBV infection in vitro and in vivo
      is not well characterized. In this experiment we infected NPC cells with EBV
      particles through endocytosis of a complex of EBV immunoglobulin A (IgA)
      secretory component (SC) protein to observe the response of host cells to the
      foreign viral infection in vitro. We found that EBV particles were endocytosed
      and stabilized in NPC nuclei 24 hours after infection; the EBV genomes were then
      gradually decreased after serial passages within 3 to 4 weeks by the following
      pathway: the EBV genomes first moved toward the nuclear envelope from the center
      of the nucleus; after crossing the nuclear envelope, they moved into the
      cytoplasm and toward the plasma membrane and were discharged by exocytosis. At
      the 10th day of EBV infection, EBV-latent membrane protein-1 and Epstein-Barr
      nuclear antigen (EBNA)-1 protein expressions could be detected, but not EBV-viral
      capsid antigen. Observation of EBNA-1 protein and host growth factor and cytokine
      gene expressions in the weeks after incubation revealed that the EBNA-1 protein
      expression was decreased proportionally with decrease of EBV genome. The mRNA
      expression of epithelial growth factor receptor, transforming growth factor (TGF)
      alpha, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony
      stimulating factor increased within 1 to 2 weeks after infection, and gradually
      recovered to the original level at 3 to 4 weeks, whereas the mRNAs of TGFbeta1,
      TGFbeta receptor type I (TGFbetaRI), TGFbetaR type II, IL-8, and tumor necrosis
      factor-alpha remained unchanged. It is concluded that in vitro EBV infection in
      NPC cells results in increase of certain growth factor and cytokine gene
      expressions in host cells. The change in gene expression returns to the original
      level approximately 3 to 4 weeks after infection because of exocytosis of EBV DNA
      by the infected cells through an unidentified mechanism.

PMID- 10950107
TI  - Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is
      related to oxidative stress and lipid peroxidation in rats.
AB  - The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in
      the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, the
      role of LP in the generation of chronic gastric mucosal injury is unknown. We
      have developed a model of chronic mucosal injury induced by continuous ethanol
      ingestion for 5 days and characterized by marked alterations in plasma membranes
      from gastric mucosa. Therefore, LP was evaluated in this experimental model.
      Indicators of peroxidative activity, mucosal glutathione content, thymidine
      kinase activity (an index of cell proliferation), and histamine H2-receptor (H2R)
      binding constants were quantified in animals undergoing gastric mucosal damage.
      The effect of famotidine, a H2R antagonist that readily ameliorates the chronic
      mucosal injury, was also tested. Increased free radicals and LP levels were
      detected during gastritis; however, a second, higher peak of LP was noted in
      mucosal plasma membranes after ethanol withdrawal (recovery period). This further
      increase of LP coincided with active cell proliferation, decreased mucosal
      glutathione levels, and diminished specific cimetidine binding by H2R.
      Administration of famotidine accelerated the mucosal proliferative process,
      inducing the second lipoperoxidative episode sooner, and preserved the content of
      glutathione. In addition, LP correlated directly with cell proliferation and
      inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be
      involved in chronic ethanol-induced gastric mucosal injury. However, a further
      enhancement of plasma membrane LP occurred, associated with increased DNA
      synthesis and diminished cimetidine binding by membrane H2R. Therefore, increased
      LP could also participate in the compensatory mucosal proliferation initiated
      after ethanol withdrawal.

PMID- 10950108
TI  - Alterations of the rat mesentery vasculature in experimental diabetes.
AB  - The alteration induced by diabetes on vascular permeability to serum albumin was
      investigated in the mesentery of streptozotocin-induced hyperglycemic rats.
      Double-tagged ((125)I and dinitrophenol-haptenated) heterologous albumin was
      intravenously administered in normal and hyperglycemic animals, and the
      extravasation of the tracer was evaluated by radioactivity measurements and by
      morphometry at the ultrastructural level using quantitative protein A-colloidal
      gold immunocytochemistry. The results demonstrate that diabetes induces a
      significant increase in the permeability of the mesentery vessels to albumin.
      This increase is due to a more efficient transport of macromolecules by
      endothelial plasmalemmal vesicles and not to leakier interendothelial junctions.
      Passage across the endothelial basement membranes did not appear to be restricted
      in either the control or diabetic condition. However, in diabetes, the
      mesothelial basement membrane appeared to become modified and to restrain the
      passage of albumin toward the peritoneal cavity. After 3 months of diabetes, the
      rats presented a net increase in the average diameter of the blood vessels
      localized in the mesentery arcada (macrovascular hyperplasy) and a notable
      angiogenesis, manifested at the level of the microvasculature in the mesenteric
      windows.

PMID- 10950109
TI  - The death domain of tumor necrosis factor receptor 1 is necessary but not
      sufficient for Golgi retention of the receptor and mediates receptor
      desensitization.
AB  - TNF signals are mediated through two different receptors, TNFR1 and TNFR2. In
      endothelial cells, TNFR1 is predominantly localized in the Golgi apparatus and
      TNFR2 on the plasma membrane. To investigate structural features responsible for
      the disparate localization, endothelial cells were transfected with epitope
      tagged or green fluorescent protein-fused wild type and mutant receptor
      molecules. Wild type receptors recapitulated the distribution of endogenous
      receptors. Deletions of the entire TNFR1 intracellular domain or of the C
      terminal death domain (TNFR1(-DD)) allowed expression of the receptor on the
      plasma membrane. However, addition of the death domain to the C-terminus of TNFR2
      (TNFR2(+DD)) did not lead to Golgi-retention of this chimeric receptor.
      Overexpressed TNFR1, TNFR2, and TNFR2(+DD) increased basal expression of a
      cotransfected NF-kappaB-dependent promotor-reporter gene. Overexpressed TNFR1(
      DD) did not activate NF-kappaB but acted as a ligand-specific dominant negative
      inhibitor of TNF actions. Unexpectedly, TNF responses were also inhibited by
      overexpressed TNFR1 and TNFR2(+DD), but not TNFR2. We conclude that the death
      domain of TNFR1 is required for retention of TNFR1 in the Golgi apparatus but is
      not sufficient to direct Golgi retention of a TNFR2(+DD) chimera, and that
      overexpressed receptors that contain the death domain (TNFR1 and TNFR2(+DD))
      spontaneously activate NF-kappaB while inhibiting TNF responses.

PMID- 10950110
TI  - Treatment with soluble VEGF receptor reduces disease severity in murine collagen
      induced arthritis.
AB  - Maintenance of the invasive pannus in rheumatoid arthritis is an integral part of
      disease progression. The synovial vasculature plays an important role in the
      delivery of nutrients, oxygen, and inflammatory cells to the synovium. Vascular
      endothelial growth factor (VEGF), an endothelial mitogen expressed by cells
      within the synovial membrane, is thought to contribute to the formation of
      synovial blood vessels. Our objective in this study was to measure the kinetics
      of VEGF production in a murine model of collagen-induced arthritis and to
      determine whether VEGF blockade reduces disease progression. Synovial cells
      isolated from the knee joints of naive or sham-immunized mice, or from mice
      immunized with collagen but without arthritis, released little or no detectable
      VEGF. Onset of arthritis was associated with expression of VEGF mRNA and protein.
      The levels of VEGF secreted by synovial cells isolated from the joints of mice
      with severe arthritis were significantly higher than from mice with mild disease.
      To block VEGF activity, animals were treated after arthritis onset with a soluble
      form of the Flt-1 VEGF receptor (sFlt), which was polyethylene glycol (PEG)
      linked to increase its in vivo half-life. Treatment of arthritic mice with sFlt
      PEG significantly reduced both clinical score and paw swelling, compared with
      untreated or control-treated (heat-denatured sFlt-PEG) animals. There was also
      significantly less joint inflammation and reduced bone and cartilage destruction
      in sFlt-PEG-treated animals, as assessed by histology. Our data demonstrate that,
      in collagen-induced arthritis, expression of the potent angiogenic cytokine VEGF
      correlates with disease severity. Furthermore, specific blockade of VEGF activity
      results in attenuation of arthritis in both macroscopic and microscopic
      parameters. These observations indicate that blood vessel formation is integral
      to the development of arthritis and that blockade of VEGF activity might be of
      therapeutic benefit in rheumatoid arthritis.

PMID- 10950111
TI  - Combined analysis of DNA ploidy, proliferation, and apoptosis in paraffin
      embedded cell material by flow cytometry.
AB  - A flow cytometric assay was developed for correlated measurement of DNA content
      and apoptotic DNA strand breaks in cell nuclei of formalin-fixed, paraffin
      embedded tissues. The assay allows a combined analysis of cell ploidy,
      proliferation, and apoptosis in sections of fixed paraffin-embedded archival or
      fresh tissue/cell specimens. It is based on (a) proteolytic release of cell
      nuclei from deparaffinized and rehydrated 90-microm thick sections of the fixed
      embedded specimen, (b) the inactivation of the protease, (c) FITC-labeling of DNA
      strand breaks by the terminal deoxynucleotidyl transferase (TdT)-mediated FITC
      dUTP nick end-labeling (TUNEL) reaction, and (d) DNA staining with 4'6-diamidino
      2-phenyleindole. The fluorescence was recorded with a double-beam flow cytometer
      equipped with a mercury arc lamp and an argon ion laser. Cytograms obtained with
      this assay correlated closely with those produced using nonembedded material from
      the same specimen. Furthermore, a significant correlation was found between flow
      cytometric analysis of apoptosis in cell nuclei released from paraffin blocks and
      conventional evaluation of TUNEL on (corresponding) sections (p < 0.001). Since
      necrotic cells can stain positively by TUNEL, the possibility to microscopically
      select nonnecrotic tumor regions for flow cytometric analysis is an important
      advantage of the assay.

PMID- 10950112
TI  - Culture of dendritic cells from a nonlymphoid organ, the thyroid gland: evidence
      for TNFalpha-dependent phenotypic changes of thyroid-derived dendritic cells.
AB  - Because they are sparsely distributed in tissues, dendritic cells (DC) present in
      nonlymphoid organs are difficult to isolate. Only DC from skin and lung have been
      successfully studied in culture. The objective of the present work was to
      investigate the possibility of isolating and culturing DC from an endocrine
      organ, the thyroid gland, which is particularly susceptible to the development of
      autoimmune processes. The study was conducted on pig thyroid glands to have
      sufficient amounts of starting material. This choice required the
      characterization of immunological reagents capable of recognizing DC markers in
      the pig species. Using a discontinuous trypsinization procedure, a DC population
      representing 2% to 3% of the thyroid cell suspension was reproducibly obtained.
      Isolated DC quantitatively attached to tissue culture-treated dishes and
      segregated from thyrocytes. DC identified as cells expressing major
      histocompatibility complex class II molecules, the mannose receptor, and the S100
      protein were found to have a high capacity to internalize labeled ligands,
      dextran, and mannosylated albumin. These cells had a phenotype of immature DC.
      Secondarily, a fraction of DC detached from culture dishes, and floating DC had
      low or no endocytic activity, a characteristic of mature DC. Treatment of
      DC/thyrocytes cocultures with tumor necrosis factor alpha (TNFalpha) activated
      the transformation of immature DC into mature DC. These data show that DC
      isolated from the thyroid gland can be maintained immature or activated to
      undergo maturation in primary culture. The procedure of cell isolation and
      culture should be adaptable to human thyroid tissue for in vitro analyses of DC
      mediated immune responses.

PMID- 10950113
TI  - Mitochondrial dysfunction in congenital nephrotic syndrome.
AB  - The molecular mechanisms maintaining the kidney glomerular filtration barrier
      remain poorly understood. Recent evidence suggests that mitochondrial dysfunction
      is a characteristic feature of kidney glomeruli in congenital nephrotic syndrome
      of the Finnish type (CNF). Here we searched for detailed functional evidence of
      mitochondrial lesion in CNF kidneys. We used histochemical and
      immunohistochemical methods, quantitative measurement of mitochondrial DNA, and
      superoxide production to characterize the mitochondrial function. The results
      unequivocally show down-regulation of mitochondria-encoded respiratory chain
      components, whereas the respective nuclearly encoded subunits were close to
      normal. These results give detailed evidence of distinct mitochondrial
      dysfunction and of the resulting abnormal production of reactive oxygen species
      in CNF and suggest a critical role for mitochondria in maintaining the glomerular
      permeability barrier.

PMID- 10950114
TI  - Galectin-1 and galectin-3 in chronic pancreatitis.
AB  - Galectin-1 and galectin-3 have important functions in cell-cell interactions,
      cell adhesion to extracellular matrix, the organization of extracellular matrix,
      and tissue remodeling. To assess their potential role in chronic pancreatitis
      (CP), we examined their expression by Northern blot analysis, in situ
      hybridization, immunohistochemistry, and Western blot analysis in normal and CP
      pancreatic tissues. Northern blot analysis revealed a 4.5-fold increase of
      galectin-1 mRNA (p < 0.01) and a 3.8-fold increase of galectin-3 mRNA (p < 0.01)
      in CP samples compared with normal controls. In situ hybridization analysis of
      normal pancreas indicated low abundance of galectin-1 mRNA in fibroblasts,
      whereas galectin-3 mRNA was moderately present in ductal cells. CP samples
      exhibited moderate to intense galectin-1 mRNA signals in fibroblasts, whereas
      galectin-3 mRNA signals were intense in the cells of ductular complexes and weak
      in the degenerating acinar cells. In addition, intense galectin-1 and galectin-3
      mRNA signals were present in nerves of normal and CP samples.
      Immunohistochemistry showed a distribution pattern of galectin-1 and galectin-3
      similar to that described for in situ hybridization. Relative quantification of
      galectin-1 and galectin-3 protein by immunoblotting revealed an increase of 3.2
      fold and 3.0-fold, respectively, in CP compared with normal controls. There was a
      significant correlation between galectin-1 and fibrosis and between galectin-3
      and fibrosis and the density of ductular complexes. Up-regulation of galectin-1
      in fibroblasts and galectin-3 in ductular complexes suggests a role of these
      lectins in tissue remodeling in CP. Galectin-1 might participate in ECM changes,
      whereas galectin-3 seems to be involved in both ECM changes and ductular complex
      formation.

PMID- 10950115
TI  - Proliferative heterogeneity in the human prostate: evidence for epithelial stem
      cells.
AB  - Clonal analysis of human prostate epithelial cells was undertaken in order to
      identify stem cells. Two types of colony were distinguished, termed type I and
      type II. Type I colonies were relatively small and irregular and contained a
      loose mixture of differentiated and undifferentiated cells. In contrast, type II
      colonies were large, round, and homogeneous, consisting almost exclusively of
      small undifferentiated and dividing cells. The colony-forming efficiency was 5.8%
      +/- 1.8 for freshly isolated epithelial cells. There were approximately 10 times
      as many type I as type II colonies and about 1 in 200 of the plated cells was
      capable of forming a type II colony. In three-dimensional culture on Matrigel,
      the type II colonies produced structures reminiscent of prostate epithelium, with
      luminal cells expressing markers of prostate epithelial differentiation,
      including the androgen receptor. On the basis of their proliferative
      characteristics and pluripotency, the type II colonies may be the progeny of stem
      cells and the type I colonies of a more differentiated transit-amplifying
      population.

PMID- 10950116
TI  - Demonstration of intermediate cells during human prostate epithelial
      differentiation in situ and in vitro using triple-staining confocal scanning
      microscopy.
AB  - In human prostate epithelium, morphologically basal and luminal cells can be
      discriminated. The basal cell layer that putatively contains progenitor cells of
      the secretory epithelium is characterized by the expression of keratins (K) 5 and
      14. Luminal cells represent the secretory compartment of the epithelium and
      express K8 and 18. We developed a technique for the simultaneous analysis of K5,
      14, and 18 to identify intermediate cell stages in the prostate epithelium and to
      study the dynamic aspects of its differentiation in vitro. Nonmalignant prostate
      tissue and primary epithelial cultures were immunohistochemically characterized
      using triple staining with antibodies for K5, K14, and K18. Antibodies for K18
      and K5 were conjugated directly with fluorochromes Alexa 488 and 546. K14 was
      visualized indirectly with streptavidin-Cy5. Keratin expression was analyzed by
      confocal scanning microscopy. The occurrence of exocrine and neuroendocrine
      differentiation in culture was determined via antibodies to prostate-specific
      antigen (PSA), chromogranin A, and serotonin. We found that basal cells expressed
      either K5(++)/14(++)/18+ or K5(++)/18+. The majority of luminal cells expressed
      K18(++), but colocalization of K5+/18(++) were recognized. Epithelial monolayer
      cultures predominantly revealed the basal cell phenotype K5(++)/14(++)/18+,
      whereas intermediate subpopulations expressing K5+/14+/18(++) and K5+/18(++) were
      also identified. On confluence, differentiation was induced as multicellular
      gland-like buds, and extensions became evident on top of the monolayer. These
      structures were composed of K18(++)- and K5+/18(+)-positive cell clusters
      surrounded by phenotypically basal cells. Few multicellular structures and cells
      in the monolayer showed exocrine differentiation (PSA+), but expression of
      chromogranin A and serotonin was absent. We conclude that simultaneous evaluation
      of keratin expression is useful for analyzing epithelial differentiation in the
      prostate. During this process, putative stem cells phenotypically resembling
      K5(++)/14(++)/18+ differentiate toward luminal cells (K18(++)) via intermediate
      cell stages, as identified by up-regulation of K18 and down-regulation of K5 and
      14.

PMID- 10950117
TI  - Differentially expressed genes in two LNCaP prostate cancer cell lines reflecting
      changes during prostate cancer progression.
AB  - Prostate cancer tends to become transformed to androgen-independent disease over
      time when treated by androgen-deprivation therapy. We used two variants of the
      human prostate cancer cell line LNCaP to study gene expression differences during
      prostate cancer progression to androgen-independent disease. Production of
      prostate-specific antigen was regarded as a marker of androgen-dependence and
      loss of prostate-specific antigen was regarded as a marker of androgen
      independence. mRNA from both cell lines was used for cDNA microarray screening.
      Differential expression of several genes was confirmed by Northern blotting.
      Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat P044, and EST
      AA412049 were highly overexpressed in androgen-dependent LNCaP cells. Tissue-type
      plasminogen activator, interferon-inducible protein p78 (MxB), an EST similar to
      galectin-1, follistatin, fatty acid-binding protein 5, EST AA609749, annexin I,
      the interferon-inducible gene 1-8U, and phospholipase D1 were highly
      overexpressed in androgen-independent LNCaP cells. All studied genes had low or
      no expression in PC-3 cells. The EST similar to rat P044, the EST similar to
      galectin-1, follistatin, annexin I, and the interferon-inducible gene 1-8U were
      also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal
      protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic
      hyperplasia tissue. Additionally, both confirmation of differential expression in
      Northern blots and in situ hybridization were carried out for monoamine oxidase
      A, the EST similar to rat P044, the EST similar to galectin-1, fatty acid-binding
      protein 5, and the interferon-inducible gene 1-8U. We identified several
      potential prostate cancer markers, indicating that the method used is a useful
      tool for the screening of cancer markers, but other methods, such as in situ
      hybridization, are needed to further investigate the observations.

PMID- 10950118
TI  - Recombinant human interleukin-11 modulates ion transport and mucosal inflammation
      in the small intestine and colon.
AB  - Human recombinant interleukin 11 (rhIL-11) is a cytokine that suppresses the
      clinical signs of colitis in animal models of inflammatory bowel disease (IBD)
      and may be an effective therapeutic agent in the treatment of IBD. The objective
      of the current study was to investigate whether rhIL-11 was capable of reversing
      abnormalities in secretomotor function associated with gut inflammation. We
      investigated the effects of rhIL-11 on epithelial electrogenic ion transport in
      the jejunum and colon. Application of rhIL-11 (10 to 10,000 ng/ml) at either the
      luminal or serosal side of mucosal sheets isolated from control rats induced a
      concentration-dependent reduction of transmural potential difference (PD) in the
      jejunum and decreased the short-circuit current (Isc), representative of active
      electrogenic transport, in the colon. To investigate the effect of rhIL-11 on an
      inflamed gut, we isolated jejunal and colonic tissue from HLA-B27 transgenic rats
      with active inflammation of the bowel that represents an animal model of IBD. In
      jejunum and colon isolated from HLA-B27 transgenic rats, basal electrogenic ion
      transport was significantly attenuated and, under these conditions, rhIL-11
      caused no changes in either transmural PD or Isc. However, in HLA-B27 rats,
      pretreatment with subcutaneous doses of rhIL-11 suppressed the symptoms of
      diarrhea, normalized myeloperoxidase activity in the jejunum and colon and healed
      mucosal injury. In the jejunum from HLA-B27 rats, healing of the intestinal
      inflammatory response enhanced basal transmural PD and the rhIL-11-duced changes
      in mucosal ion transport resembled those seen in uninflamed controls. Conversely,
      in the colon, healing of the mucosa did not normalize basal active ion transport
      nor did it reverse the inhibition of rhIL-11-induced changes in colonic Isc. Our
      results suggest that endogenous IL-11 may act as a modulator of epithelial
      transport under physiologic conditions and may act as a potent anti-inflammatory
      cytokine during active intestinal inflammation.

PMID- 10950119
TI  - Dermal organization in scleroderma: the fast Fourier transform and the laser
      scatter method objectify fibrosis in nonlesional as well as lesional skin.
AB  - Scleroderma, a chronic, progressive disorder, is characterized by dermal fibrosis
      with collagen bundles orientated parallel to the epidermis. Simple objective
      parameters to evaluate disease progression and therapies are needed. We describe
      two methods, the laser scatter method and the fast Fourier transform (FFT), to
      measure collagen bundle orientation and spacing. Lesional sclerodermic skin (LS),
      nonlesional sclerodermic skin (nonLS), and control skin (CS) sections were
      evaluated for orientation ratio using the laser scatter method. The FFT was used
      to calculate orientation ratio, variation, and spacing of collagen bundles.
      Parameters were correlated with local and mean skin score measurements, on a
      scale of 0 (normal) to 3 (severely sclerotic). With both the laser scatter method
      and the FFT, orientation ratios of LS (respectively, 2.16 +/- 0.33 and 1.83 +/-
      0.62) were significantly higher than CS (respectively, 1.70 +/- 0.35 and 1.38 +/-
      0.15). NonLS orientation ratios (respectively, 1.92 +/- 0.15 and 1.48 +/- 0.44)
      were between LS and CS ratios. Orientation variation and bundle spacing of LS
      (respectively, 57.3 +/- 19.4 and 15.7 +/- 5.6 microm) were significantly reduced
      compared to CS (respectively, 73.8 +/- 15.0 and 18.9 +/- 1.9 microm). NonLS
      orientation ratios (respectively, 57.2 +/- 29.0 and 15.6 +/- 6.1 microm) were
      similar to LS. Bundles in LS are more parallel, show less variation in
      orientation, and are more densely packed than in CS. There was a linear
      correlation between mean skin score and orientation ratio. Local skin score was
      not linearly correlated to orientation ratio. Our findings suggest that nonLS
      dermis without clinical sclerosis already shows fibrotic characteristics. Both
      techniques were easy to use and suitable for objectifying dermal fibrosis in
      scleroderma lesions. FFT is more accurate and reproducible than the laser scatter
      method and allows simultaneous pathological evaluation of the location of the
      analyzed tissue sections. Future studies will need to focus on the correlation
      between clinical disease severity and collagen bundle characteristics.

PMID- 10950120
TI  - Silencing of CD44 expression in prostate cancer by hypermethylation of the CD44
      promoter region.
AB  - Loss of the CD44 transmembrane glycoprotein in primary prostate cancer has been
      shown to be associated with unfavorable clinical behavior. Moreover, the majority
      of prostate cancer metastases lack expression of this molecule. The mechanism of
      CD44 silencing in prostate cancer was investigated using both patient material
      and in vivo-propagated human prostate cancer xenografts. In 9 of 11 lymph node
      metastases of prostate cancer, we demonstrated by methylation-sensitive
      restriction enzyme digestion that the promoter region of the CD44 gene is
      methylated, indicating that this represents a major mechanism of CD44 silencing.
      Similarly, in 6 out of 12 in vivo-growing human prostate carcinoma xenograft
      models, hypermethylation of the CD44 gene was found. The extent of CpG island
      methylation was investigated by nucleotide sequencing after bisulphite
      modification of the CD44 promoter region. In the xenografts displaying
      hypermethylation, the examined 14 CpG sites in the CD44 transcription regulatory
      domain, including a Sp1 binding site, were consistently methylated. This
      correlated with reduced CD44 expression or lack of CD44 expression at mRNA and
      protein levels. In the xenografts lacking hypermethylation of the CD44 gene, high
      levels of CD44 mRNA and protein were expressed in some models, whereas in others
      CD44 mRNA expression was only detectable by RT-PCR and the CD44 protein could
      hardly be detected or was not detected at all. The results indicate that, in most
      prostate cancers, loss of CD44 expression is associated with extensive
      hypermethylation of the CpG island of the CD44 promoter region, but other,
      posttranscriptional mechanisms may also lead to CD44 loss.

PMID- 10950121
TI  - Local immune response in skin of generalized vitiligo patients. Destruction of
      melanocytes is associated with the prominent presence of CLA+ T cells at the
      perilesional site.
AB  - In situ immune infiltrates in lesional, perilesional, and nonlesional skin
      biopsies from patients with vitiligo were analyzed by immunohistochemistry and
      compared with immune infiltrates found in the skin of normal healthy donors and
      relevant disease controls. An increased influx of activated skin-homing T cells
      and macrophages were seen in the perilesional biopsies. The overall percentages
      of cutaneous leukocyte-associated antigen-positive (CLA+) T cells were similar to
      those found in normal healthy donors. This is compatible with the similar
      expression of E-selectin. Most strikingly, however, the CLA+ T cells in
      perilesional skin were mainly clustered in the vicinity of disappearing
      melanocytes, and 60% to 66% of these interacting T cells expressed perforin and
      granzyme-B. The perforin+/granzyme-B+ cells were not seen in locations different
      from that of disappearing melanocytes. Interestingly, the majority of the
      infiltrating T cells were HLA-DR/CD8+. Another hallmark of the present study is
      the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in
      the epidermis at the site of interaction between the immune infiltrates and the
      disappearing melanocytes. The data presented in this study are consistent with a
      major role for skin-homing T cells in the death of melanocytes seen in vitiligo.

PMID- 10950122
TI  - Interaction of endothelin-1 with vasoactive factors in mediating glucose-induced
      increased permeability in endothelial cells.
AB  - Alteration of endothelins (ET) and/or their receptors may be important in
      mediating vascular dysfunction in diabetes. We investigated mechanisms regulating
      ET-1 expression in human umbilical vein endothelial cells (HUVEC) in response to
      glucose and the functional significance of these mechanisms. Permeability across
      HUVEC, grown in medium containing either low (5 mmol/l) or high (25 mmol/l) D
      glucose were investigated. L-glucose was used as a control. ET-1, ET(A), and
      ET(B) mRNA were assessed by semiquantitative RT-PCR. ET-1 immunoreactivity and F
      actin microfilament assembly were investigated using confocal microscopy.
      Increased transendothelial permeability was noted in cells cultured in high
      glucose or when the cells grown in low (physiologic) glucose were incubated with
      ET-1, vascular endothelial growth factor (VEGF), or N (G) -nitro-L-arginine
      methyl ester but not when they were incubated with ET-3, N(G)-nitro-D-arginine
      methyl ester, or L-glucose. Increased permeability was associated with increased
      ET-1, ET(A), and ET(B) mRNA expression and augmented ET-1 immunoreactivity. High
      glucose induced increased permeability, increased ET-1, ET(A), and ET(B) mRNA
      expression. ET-1 immunoreactivity was blocked by the protein kinase C (PKC)
      inhibitor chelerythrine, the specific PKC isoform inhibitor 379196, VEGF
      neutralizing antibody, or the ET(A) blocker TBC11251, but was not blocked by the
      specific ET(B) blocker BQ788 or by a VEGF-non-neutralizing antibody. Increased
      permeability was also associated with deranged F-actin assembly in the
      endothelial cells and by derangement of endothelial cell junctions as assessed by
      electron microscopy. Data from this study suggest that high glucose-induced
      increased permeability may be induced through increased ET-1 expression and
      disorganization of F-actin assembly. ET-1 expression and increased permeability
      may occur secondary to PKC isoform activation and may be modulated by VEGF and
      nitric oxide.

PMID- 10950123
TI  - Mitochondrial DNA damage as a mechanism of cell loss in Alzheimer's disease.
AB  - Aging is associated with impaired mitochondrial function caused by accumulation
      of oxygen free radical-induced mitochondrial (Mt) DNA mutations. One prevailing
      theory is that age-associated diseases, including Alzheimer's disease (AD), may
      be precipitated, propagated, or caused by impaired mitochondrial function. To
      investigate the role of MtDNA relative to genomic (Gn) DNA damage in AD, temporal
      lobe samples from postmortem AD (n = 37) and control (n = 25) brains were
      analyzed for MtDNA and GnDNA fragmentation, mitochondrial protein and cytochrome
      oxidase expression, MitoTracker Green fluorescence (to assess mitochondrial
      mass/abundance), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG)
      immunoreactivity. Brains with AD had more extensive nicking and fragmentation of
      both MtDNA and GnDNA as demonstrated by agarose gel electrophoresis, end
      labeling, and the in situ terminal deoxynucleotide transferase end-labeling
      (TUNEL) assay, and only the brains with AD had detectable 8-OHdG immunoreactivity
      in cortical neurons. Increased MtDNA damage in AD was associated with reduced
      MtDNA content, as demonstrated by semiquantitative PCR analysis and reduced
      levels of Mt protein and cytochrome oxidase expression by Western blot analysis
      or immunohistochemical staining with image analysis. The finding of reduced
      MitoTracker Green fluorescence in AD brains provided additional evidence that
      reduced Mt mass/abundance occurs with AD neurodegeneration. The presence of
      increased MtDNA and GnDNA damage in AD suggest dual cell death cascades in AD.
      Impaired mitochondrial function caused by MtDNA damage may render brain cells in
      AD more susceptible to oxidative injury and thereby provide a mechanism by which
      systemic or environmental factors could influence the course of disease.

PMID- 10950124
TI  - Implication of interleukin-4 in wound healing.
AB  - Interleukin-4 (IL-4) is a pleiotropic cytokine that is able to activate
      connective tissue cells and stimulate the accumulation of extracellular matrix
      macromolecules. In this report, the expression of IL-4 in normal wound healing
      was studied by immunohistochemistry. The effects of exogenous IL-4 or IL-4
      antisense oligonucleotides administration were also studied in mouse experimental
      wounds. IL-4 expression was detected in the lower dermis below the wound as early
      as Day 1 after wounding. IL-4 expression was maximal by Day 4, then decreased
      progressively, and completely disappeared by Day 21 after wounding. Topical
      administration of IL-4 on experimental wounds in mice significantly accelerated
      the rate of healing, whereas IL-4 antisense oligonucleotides significantly
      inhibited healing. These results demonstrate that IL-4 may be implicated in
      normal wound healing.

PMID- 10950125
TI  - Medicines availability--the millennium muddle.

PMID- 10950126
TI  - Testing for bovine tuberculosis--more than skin deep.

PMID- 10950127
TI  - The threat to the European honeybee (Apis mellifera) and the importance of a
      sound veterinary approach.

PMID- 10950128
TI  - Optimization of bovine reproduction efficiency.

PMID- 10950129
TI  - Molecular genetics and canine health.

PMID- 10950130
TI  - Aerosol therapy in veterinary medicine: is it the future?

PMID- 10950131
TI  - Evaluation of the specificity of the gamma-interferon test in Italian bovine
      tuberculosis-free herds.
AB  - We investigated the specificity of the gamma-interferon test for bovine
      tuberculosis (TB) in 1,557 cattle in 30 paratuberculosis-free and officially
      certified TB-free dairy herds, located in three provinces of the Lombardy Region
      in Northern Italy. The TB-free status of the herds under examination was further
      confirmed by the tuberculin skin test, by an antibody assay and by post mortem
      examination of animals culled from the herds during the study period. The
      specificity of the gamma-interferon tests after a single test and a double
      sampling scheme were 88.8% and 95.4%, respectively. After a single test, 11.7% of
      dubious reactors were also detected, while most cattle (47.4%) were shown to be
      avian reactors, probably due to contamination from infected birds and/or forage.
      There was strong evidence that the specificity of the test could be related to
      the animals' interaction with environmental mycobacteria and/or ageing. To reduce
      the percentage of nonspecific bovine reactors under alleged TB-free conditions,
      test procedures might involve the use of more specific antigens and/or different
      reaction thresholds.

PMID- 10950132
TI  - Comparison between radioactive aerosol, technegas and krypton for ventilation
      imaging in healthy calves.
AB  - The use of lung scintigraphy in calves necessitates the validation of a
      ventilation (V) imaging agent compatible with clinical applications. This study
      aimed at defining the value of an inhaled radioactive aerosol (99mTc-DTPA) and a
      'pseudogas' (Technegas) in the assessment of regional V in healthy conscious
      calves by comparing 99mTc-DTPA and Technegas deposition (D) images to V(V) images
      obtained from the steady-state inhalation of the short half-life krypton 81
      (81mKr) gas. Images were compared by analysis of radioactivity distribution in
      computer-generated regions of interest within the right lung and D to V ratio
      images were generated in order to highlight areas of mismatching between 99mTc
      DTPA or Technegas and 81mKr distributions. Results of this analysis showed that
      the 99mTc-DTPA aerosol droplets were unable to reach the lung parenchyma because
      of significant particle impaction in the major conducting airways. Better
      definition of the ventilated lung was obtained when using Technegas because of
      minimal deposition in conducting airways. Furthermore, the Technegas and 81mKr
      distribution patterns were highly equivalent.

PMID- 10950133
TI  - Effects of acute pain reduction methods on the chronic inflammatory lesions and
      behaviour of lambs castrated and tail docked with rubber rings at less than two
      days of age.
AB  - Lesions were produced by castration and tail docking of two-day-old Dorset-cross
      lambs with elastrator rings with (RRla) and without (RR) local anaesthetic or
      after destruction of the innervation by crushing close to the ring (Brr). The
      lesions were monitored twice weekly for six weeks and the behaviour of handled
      controls (H), RR and RRla lambs was recorded for two 3 h periods 10, 20, 31 and
      41 days after treatment. There was no significant effect of castration and tail
      docking, with or without pain reduction methods, on daily liveweight gain. In the
      Brr lambs, the dead tails were cast 10 days earlier than from RR and RRla lambs.
      The time taken for the scrotal lesion to reach maximum severity was halved in Brr
      and RRla lambs, although the maximum severity of the lesion was unaffected by the
      methods of pain reduction. During the four 6 h behavioural observation periods,
      RR lambs showed a significant increase in the mean (+/- sd) frequency of foot
      stamping (RR13 +/- 13; H2 +/- 2.5), tail wagging (61 +/- 26; 15 +/- 6), head
      turning to the scrotum and inside hind-leg (12 +/- 10; 1 +/- 1). Less abnormal
      behaviour was found after RRla than after RR treatment. This unexpected finding
      may be evidence of long-lasting increases in pain sensitivity after an episode of
      intense acute pain in young animals.

PMID- 10950134
TI  - Molecular markers and their use in animal breeding.
AB  - The use of DNA markers to define the genetic makeup (genotype) and predict the
      performance of an animal is a powerful aid to animal breeding. One strategy is
      known as marker-assisted selection (MAS). MAS facilitates the exploitation of
      existing genetic diversity in breeding populations and can be used to improve a
      whole range of desirable traits. DNA markers are, by definition, polymorphic, and
      the methods used to define DNA markers include restriction fragment length
      polymorphisms (RFLPs), microsatellites, and single nucleotide polymorphisms
      (SNPs). Linkage analysis, association analysis and analysis of gene function can
      be used to determine which polymorphisms are useful markers for desirable traits.
      Future prospects include the use of high throughput DNA microarray (DNA chip)
      technology which could revolutionize animal breeding in the next millennium.

PMID- 10950135
TI  - Strategies for reversing the trend towards subfertility in dairy cattle.
AB  - The calving rate of the modern dairy cow is declining at approximately 1% per
      annum. First service conception rates are now below 40%, and the average cow
      requires more than two inseminations to get her in calf. We review here genetic,
      endocrine and nutritional strategies for reducing subfertility, and we emphasize
      the role of milk progesterone data in the analysis of the condition. Milk
      progesterone data underpin three approaches to treating subfertility; firstly,
      they allow the identification of specific reproductive abnormalities which can be
      treated pharmacologically. Secondly, they show that at least one endocrinopathy
      is heritable, thereby providing the basis for a selective breeding strategy.
      Thirdly, they provide a means for monitoring ovarian (and indirectly uterine and
      conceptus) function during early pregnancy, which are central to the successful
      establishment of pregnancy, and are amenable to dietary modification. These
      approaches to reversing the falling fertility of dairy cows are characterized by
      different timescales.

PMID- 10950136
TI  - A veterinary approach to the European honey bee (Apis mellifera)
AB  - The European honey bee (Apis mellifera) has the unusual status of being an
      inherently wild species from which a natural foodstuff (honey) is derived by
      manipulating its behaviour to deposit this in man-made wooden frames. Bees also
      produce propolis and Royal Jelly which can be harvested but their most important
      effect is one not immediately obvious as an economic product: that of
      pollination. Bee diseases are predominantly infectious and parasitic conditions
      accentuated by the close confinement in which they congregate, either in man-made
      hives or in colonies in a natural cavity. Treatment or at least control of some
      of these conditions can be attempted. In some cases natural bee behavioural
      traits limit the effect of the disease while in others, such as the notifiable
      disease American foulbrood, destruction of the colony is the only method of
      control. The mite Varroa jacobsoni can be controlled by the synthetic pyrethroids
      flumethrin and tau-fluvalinate. The introduction of these products has heightened
      veterinary interest in this important invertebrate species.

PMID- 10950137
TI  - Orf infection in four sheep flocks.

PMID- 10950138
TI  - Comparative genomic hybridization (CGH) in dogs--application to the study of a
      canine glial tumour cell line.
AB  - Recurrent chromosome aberrations are associated with many human cancers. Detailed
      cytogenetic analysis of tumors has benefited enormously from the development of
      molecular cytogenetic techniques based on fluorescence in situ hybridization
      (FISH). Comparative genomic hybridization (CGH) is a recently developed FISH
      technique that allows a rapid and comprehensive identification of imbalanced
      genomic material in tumour DNA. Comparative genomic hybridisation has been used
      widely in human medicine to evaluate losses and gains of tumour DNA isolated from
      a variety of sources, including fresh samples, cell-culture material and archival
      specimens, and has been instrumental in identifying sites in the human genome
      which contain genies involved in tumour development and progression. This report
      describes the first application of CGH in the dog, illustrated by the analysis of
      DNA isolated from a canine glial tumour cell line.

PMID- 10950139
TI  - Exploitation of the B cell repertoire for the identification of human tumor
      antigens.
AB  - The screening of tumor-derived expression libraries for antigens that are
      detected by high-titer immunoglobulin G antibodies from the sera of patients with
      cancer using serological identification of antigens by recombinant expression
      cloning (SEREX) allows for the systematic search for antigens of human cancers.
      SEREX has led to the identification of a plentitude of new tumor antigens in many
      different tumor entities. These antigens, many of which are encoded by hitherto
      unknown genes, can be grouped into different classes. Serologically defined human
      tumor antigens facilitate the identification of antigenic peptides recognized by
      tumor-specific T lymphocytes, thus providing a molecular basis for polyvalent
      peptide-based and gene therapeutic vaccine strategies in a wide variety of human
      neoplasms. Finally, many of the antigens identified using SEREX seem to play a
      functional role in the pathogenesis of malignant disease.

PMID- 10950140
TI  - Recombinant anti-carcinoembryonic antigen antibodies for targeting cancer.
AB  - Antibodies can be used to target cancer therapies to malignant tissue; the
      approach is attractive because conventional treatments such as chemo- and
      radiotherapy are dose limited due to toxicity in normal tissues. Effective
      targeting relies on appropriate pharmacokinetics of antibody-based therapeutics,
      ideally showing maximum uptake and retention in tumor and rapid clearance from
      normal tissue. We have studied the factors influencing these dynamics for
      antibodies against carcinoembryonic antigen (CEA). Protein engineering of anti
      CEA antibodies, in vivo biodistribution models, and mathematical models have been
      employed to improve understanding of targeting parameters, define optimal
      characteristics for the antibody-based molecules employed, and develop new
      therapies for the clinic. Engineering antibodies to obtain the desired
      therapeutic characteristics is most readily achieved using recombinant antibody
      technology, and we have taken the approach of immunizing mice to provide high
      affinity anti-CEA single-chain Fv antibodies (sFvs) from filamentous
      bacteriophage libraries. MFE-23, the most characterized of these sFvs, has been
      expressed in bacteria and purified in our laboratory for two clinical trials: a
      gamma camera imaging trial using 123I-MFE-23 and a radioimmunoguided surgery
      trial using 125I-MFE-23, where tumor deposits are detected by a hand-held probe
      during surgery. Both these trials showed that MFE-23 is safe and effective in
      localizing tumor deposits in patients with cancer. We are now developing fusion
      proteins that use the MFE-23 antibody to deliver a therapeutic moiety; MFE-23::
      carboxypeptidase G2 (CPG2) targets the enzyme CPG2 for use in the antibody
      directed enzyme prodrug therapy system and MFE::tumor necrosis factor alpha
      (TNFalpha) aims to reduce sequestration and increase tumor concentrations of
      systemically administered TNFalpha.

PMID- 10950142
TI  - Targeted therapy of acute myeloid leukemia with monoclonal antibodies and
      immunoconjugates.
AB  - Traditional chemotherapy for acute leukemia often causes life-threatening toxic
      effects due to a lack of specificity for hematopoietic cells. Monoclonal
      antibodies and fusion proteins that target cell surface antigens on leukemic
      blasts are being evaluated for their cytotoxic effects and as a means of
      delivering chemotherapeutic agents or radiation directly to malignant cells. It
      is hoped that this strategy might selectively ablate malignant cells without many
      of the toxic effects commonly associated with conventional chemotherapy. In acute
      myeloid leukemia (AML), the cell surface antigens CD33 and CD45 are especially
      suitable targets. Although CD33 is expressed on AML blast cells from about 90% of
      patients, normal hematopoietic stem cells lack this antigen, as do essentially
      all nonhematopoietic tissues. For that reason, anti-CD33 antibodies have been
      created to target malignant myeloid and immature normal cells selectively while
      sparing normal stem cells. Anti-CD33 antibodies have also been used to deliver
      radiation or a cytotoxic agent directly to leukemic cells. Since the vast
      majority of leukemias and normal stem cells express the cell surface antigen
      CD45, another targeting approach allows the delivery of myeloablative radiation
      to bone marrow and spleen, common sites of leukemic involvement. Consequently,
      131I-labeled anti-CD45 antibody has been combined with traditional preparative
      regimens for patients receiving bone marrow transplantation for acute leukemia.
      Finally, fusion proteins such as those combining diphtheria toxin with
      granulocyte-macrophage colony-stimulating factor (GM-CSF) to target the GM-CSF
      receptor are now being evaluated in clinical trials. Both unconjugated and
      conjugated antibodies have shown promise in early clinical trials, and may
      represent appealing therapeutic alternatives for patients with AML.

PMID- 10950141
TI  - Recombinant antibodies against ganglioside expressed on tumor cells.
AB  - Several gangliosides such as GM2, GD2, and GD3 have been thought of as target
      molecules for active or passive immunotherapy of human cancers because of their
      dominant expression on the tumor cell surface, especially in tumors of
      neuroectodermal origin. We established a number of mouse or rat monoclonal
      antibodies (mAbs) to a series of gangliosides to investigate the nature of the
      molecules on the cell surface. Some of those mAbs were converted to chimeric or
      humanized mAbs with the aim of developing immunotherapy for human cancer. It is
      desirable for mAbs to remain on the cell surface for a long time so that they can
      exert effector functions such as complement-dependent cytotoxicity (CDC) and
      antibody-dependent cellular cytotoxicity (ADCC). We found that mAbs to GM2, GD2,
      and GD3 remain on the cell surface for > or =60 min after binding, while mAbs to
      other types of carbohydrate such as sialy Le(a) are quickly internalized. A
      chimeric mAb to GD3, KM871, was generated by linking cDNA sequences encoding
      light- and heavy-chain variable regions of mouse mAb KM641 with cDNAs encoding
      the constant region of human immunoglobulin gamma1 (IgG-1). KM871 bound to a
      variety of tumor cell lines, especially melanoma cells, including some cell lines
      to which R24 failed to bind. In a preclinical study, intravenous injection of
      KM871 markedly suppressed tumor growth and radiolabeled KM871 efficiently
      targeted the tumor site in a nude mouse model. This chimeric mAb is being
      evaluated in a phase I clinical trial in melanoma patients. The chimeric mAb
      KM966 and humanized mAb KM8969 to GM2 originated from a mouse IgM mAb. When human
      serum and human peripheral blood mononuclear cells were used as effectors in CDC
      and ADCC, respectively, KM966 and KM8969 killed GM2-expressing tumor cells
      effectively. In addition, these mAbs may induce apoptosis of a small cell lung
      cancer cell line cultured under conditions mimicking physiological tumor
      conditions.

PMID- 10950143
TI  - An immunotherapeutic approach to treatment of breast cancer: focus on trastuzumab
      plus paclitaxel. Breast Cancer Medicine Service.
AB  - Recent emphasis has focused on the development of an immunotherapeutic approach
      toward the treatment of breast cancer. In particular, evaluation of antibodies
      and vaccines are active areas of research. The monoclonal antibody trastuzumab
      (H), directed against the HER-2/neu protein, has resulted in inhibition of tumor
      growth in both preclinical and clinical studies. This effect can be increased
      when used in combination with several chemotherapeutic agents. A randomized trial
      of chemotherapy alone versus chemotherapy plus H in untreated metastatic breast
      cancer patients found prolonged survival in the combination therapy arm. Cardiac
      toxicity was increased with doxorubicin and cyclophosphamide plus H but not for
      paclitaxel (T) plus H. Several trials of dose-dense weekly T have found minimal
      toxicity and significant clinical benefit. These findings prompted the initiation
      of a trial to evaluate weekly 1-h T plus weekly H. Preliminary data from this
      ongoing study demonstrate few side effects and a response rate of 64% (95%CI 42
      76%). The optimal role of H in the treatment of breast cancer has not yet been
      defined. Additional evaluation in the metastatic and adjuvant settings is
      planned.

PMID- 10950144
TI  - Organ-specific expression of the intestinal epithelium-related antigen A33, a
      cell surface target for antibody-based imaging and treatment in gastrointestinal
      cancer.
AB  - Murine monoclonal antibody A33 (mA33) was developed by the Memorial Sloan
      Kettering Cancer Center and by the New York Branch of the Ludwig Institute for
      Cancer Research. It is an immunoglobulin (Ig)G2a antibody that detects a protease
      and neuraminidase-resistant, periodate-sensitive epitope. Serological analysis
      of the antigen showed that it is expressed in a few colorectal cancer cell lines
      and a pancreatic cancer cell line, but is basically not reactive with other types
      of cell line. Normal fibroblasts and normal kidney cell lines reacted negatively
      to mA33. Immunohistochemical study of normal tissues identified the large and
      small intestinal mucosa as the principal site of A33 expression. Tests in tumor
      samples demonstrated that only tumors of the gastrointestinal tract are
      consistently A33 positive. A33 is found in 95% of primary and metastatic
      colorectal cancers, with uniform expression throughout the tumors in most cases.
      A33 is also detected in 63% of gastric cancers, with uniform expression in 45% of
      cases. Eighty-three percent of intestinal-type gastric cancers were positive for
      A33, and about 50% of the diffuse-type and mucinous cancers were mA33 positive.
      A33 was expressed in 50% of the pancreatic cancers but with marked heterogeneity.
      Other epithelial cancers, sarcomas, neuroectodermal tumors, and lymphoid
      neoplasms were generally A33 negative. A33 is the first example of a
      constitutively expressed, organ-specific epithelial membrane antigen permitting
      highly specific tumor targeting in patients with gastrointestinal cancer.
      Encouraged by the success of the biodistribution and imaging characteristic
      studies performed at Memorial Sloan-Kettering Cancer Center by the New York
      Branch of the Ludwig Institute in colorectal cancers, a new clinical study of
      humanized monoclonal antibody huA33 against A33 antigen-positive gastric cancers
      has been initiated in Japan.

PMID- 10950145
TI  - Immune recruitment by bispecific antibodies for the treatment of Hodgkin disease.
AB  - For the treatment of Hodgkin lymphoma, bispecific monoclonal antibodies (bi-mAbs)
      were established which recognize the Hodgkin-associated CD30 antigen with one arm
      and the CD3 or CD28 antigen on T lymphocytes or the CD16 antigen on natural
      killer (NK) cells with the second arm. The NK cell-activating alpha-CD16/CD30
      antibody was able to retarget human NK cells toward CD30- target cells and induce
      their lysis. Sixty percent of Hodgkin tumor-bearing severe combined
      immunodeficient mice responded to a combined treatment with bi-mAb and human NK
      cells, leading to a final cure rate of 20%. T cell-activating bi-mAbs were more
      effective, resulting in the cure of all mice treated. The in vivo administration
      of both alpha-CD3/CD30 and alpha-CD28/CD30 antibodies resulted in the specific
      activation of resting human T cells infiltrating the CD30+ Hodgkin tumors. Tumor
      infiltrating lymphocytes in the group of mice treated with both T cell-activating
      bi-mAbs expressed high levels of cytokines and cytotoxic molecules such as
      perforin and the cytotoxic serine esterases granzyme A and B. More importantly,
      activated T cells did not home to CD30 tissue and did not enter the circulation.
      Encouraged by these preclinical data, 15 patients with treatment-refractory
      Hodgkin lymphoma were included in a phase I/II dose-escalation study and treated
      four times every 3 or 4 days with increasing doses of the alpha-CD16/CD30 bi-mAb
      ranging from 1 mg/m2 to 128 mg/m2. No dose-limiting toxicity occurred even at the
      highest doses. Of these 15 patients, one had a complete response, one a partial
      response, three a mixed response, two stable disease, and eight patients had
      progressive disease. Treatment with immunological effector cell-recruiting bi
      mAbs is a promising new approach to the treatment of Hodgkin disease refractory
      to standard therapy.

PMID- 10950146
TI  - SEREX analysis of gastric cancer antigens.
AB  - Stomach cancer is the major malignancy in Japan and one of the most common
      cancers worldwide. To establish the basis for an immunotherapeutic approach to
      stomach cancer, we have initiated an analysis of stomach cancer antigens
      recognized by human immunoglobulin G (IgG) antibodies using SE-REX, a powerful
      expression cloning method developed by Dr. M. Pfreundschuh's group. Five stomach
      cancer cDNA libraries have been screened with autologous patient sera: one
      moderately differentiated adenocarcinoma; two poorly differentiated
      adenocarcinomas; and two scirrhous-type poorly differentiated adenocarcinomas of
      Borrmann type 4, the most devastating form of stomach cancer. Based on the
      reactivities of clones with autologous IgG antibodies, an average of 50
      independent clones from each library and a total of 297 clones were isolated. DNA
      sequencing revealed that these 297 clones were derived from 136 different genes.
      Comparison of the 136 genes to sequences in DNA databases showed that 95 are
      previously identified genes and 41 are newly identified in this study. The
      antigens are derived from various genes including a chimeric gene between E
      cadherin and an unknown gene Y, AKT oncogene, genes overexpressed in stomach
      cancers, genes of which the transcripts are alternatively or aberrantly spliced,
      and genes known to be involved in autoimmune diseases. Thus stomach cancer
      patients can generate an immune response against a surprisingly diverse set of
      gene products. To identify antigens potentially useful in the diagnosis and
      therapy of gastric cancer, all 136 genes were tested for their reactivities with
      a panel of sera from 44 gastric cancer patients (17 women and 27 men, aged 35-81
      years) and with a panel of sera from 100 control individuals with no previous
      history of cancer but some of whom had gastritis (55 women and 45 men, aged 30-69
      years). Eleven antigens showed reactivity only with a certain proportion of
      cancer patient sera but not with any control sera. An additional 12 antigens
      elicited antibody production at a much higher frequency in cancer patients than
      in control individuals. To evaluate the clinical usefulness of these antigens we
      are now examining their expression in normal and malignant tissues.

PMID- 10950147
TI  - Problems in the development of target-based drugs.
AB  - Numerous molecular targets of cancer chemotherapy have been identified based on
      progress made in molecular biology, and new categories of anticancer drugs have
      been developed. These include inhibitors for signal transduction, cyclin
      dependent kinase, angiogenesis, and matrix metalloproteinase, gene therapy, etc.
      They are variously called target-based drugs, noncytotoxic drugs, or cytostatic
      drugs. Such drugs have interesting mechanisms of action and appear promising.
      However, preclinical and clinical evaluations are difficult. Some drugs have a
      direct antitumor effect, with demonstrated tumor shrinkage. Others show no direct
      cytotoxicity. The majority of recent phase I trials have evaluated the maximum
      tolerated dose, pharmacokinetics, adverse events, and antitumor effect. Unusual,
      unacceptable toxicities have been noted with some target-based drugs. Few phase I
      trials or preclinical studies have attempted to demonstrate target inhibition. So
      far very few studies has shown that there is a correlation between target
      inhibition and antitumor effect. In general, phase II studies are undertaken with
      compounds such as trastuzumab which have direct antitumor activity. Phase III
      trials of most target-based drugs are undertaken immediately after phase I
      studies since the design of appropriate phase II studies is difficult. The
      ultimate endpoint of phase III trials of target-based drugs is the same as that
      for cytotoxic drugs, such as improved cure and survival rates.

PMID- 10950148
TI  - Cancer immunotherapy in clinical oncology.
AB  - The identification of tumor-associated antigens recognized by cellular or humoral
      effectors of the immune system has opened new perspectives for cancer therapy.
      Different groups of cancer-associated antigens have been described as targets for
      cytotoxic T lymphocytes (CTLs) in vitro and in vivo: 1) cancer-testis (CT)
      antigens, which are expressed in different tumors and normal testis; 2)
      melanocyte differentiation antigens; 3) point mutations of normal genes; 4)
      antigens that are overexpressed in malignant tissues; and 5) viral antigens.
      Clinical studies with peptides derived from these antigens have been initiated to
      induce specific CTL responses in vivo. Immunological and clinical parameters for
      the assessment of peptide-specific reactions have been defined, i.e., delayed
      type hypersensitivity (DTH), CTL, autoimmmune, and tumor regression responses.
      Preliminary results demonstrate that tumor-associated peptides alone elicit
      specific DTH and CTL responses leading to tumor regression after intradermal
      injection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was proven
      effective in enhancing peptide-specific immune reactions by amplification of
      dermal peptide-presenting dendritic cells. Long-lasting complete tumor
      regressions have been observed after induction of peptide-specific CTLs. However,
      in single cases with disease progression after an initial tumor response, either
      a loss of the respective tumor antigen targeted by CTLs or of the presenting
      major histocompatibility complex (MHC) class I allele was detected as a mechanism
      of immune escape under immunization. Based on these observations, cytokines to
      enhance antigen and MHC class I expression in vivo are being evaluated to prevent
      immunoselection. Recently, a strategy utilizing spontaneous antibody responses to
      tumor-associated antigens (SEREX) has led to the identification of a new CT
      antigen, NY-ESO-1, which is regarded as one of the most immunogenic antigens
      known today inducing spontaneous immune responses in 50% of patients with NY-ESO
      1-expressing cancers. Clinical studies involving antigenic constructs that induce
      both antibody and CTL responses will show whether these are more effective for
      immunotherapy of cancer.

PMID- 10950149
TI  - The critical role of Th1-dominant immunity in tumor immunology.
AB  - To investigate the precise role of antigen-specific Th1 and Th2 cells in tumor
      immunity, we developed a novel adoptive tumor-immunotherapy model using OVA
      specific Th1 and Th2 cells and an OVA gene-transfected tumor. This therapeutic
      model demonstrated that both antigen-specific Th1 and Th2 cells had strong
      antitumor activity in vivo with distinct mechanisms. However, immunological
      memory suitable for the generation of tumor-specific cytotoxic T lymphocytes was
      induced only when tumor-bearing mice received Th1 cell therapy, but not Th2 cell
      therapy. Thus it was strongly suggested that Th1-dominant immunity is critically
      important for the induction of antitumor cellular immunity in vivo. We also
      proposed that several immunomodulating protocols using interleukin (IL)-12, IL-12
      gene, the natural killer T cell ligand alpha-galactosylceramide, or Th1 cytokine
      conditioned dendritic cells might be useful strategies for the induction of Th1
      dominant immunity essential for the development of tumor-specific immunotherapy.

PMID- 10950150
TI  - Melanoma vaccines: the paradox of T cell activation without clinical response.
AB  - In recent years significant progress in the understanding of the immune biology
      of melanoma has evolved from the identification of melanoma antigens (MAs)
      recognized by T cells. MAs consist of intracellular proteins that are expressed
      on the surface of cancer cells in association with human leukocyte antigen (HLA)
      class I molecules and therefore are suitable targets for cytotoxic T lymphocytes
      (CTLs). Several new monitoring strategies have been implemented to evaluate the
      status of activation and localization of vaccine-induced T cells in the
      peripheral circulation as well as the tumor site, including limiting dilution, in
      vitro sensitization, and ELISPOT. Previous studies aimed at monitoring patients
      receiving vaccination have utilized mainly those three methods. These methods
      have demonstrated that antigen-specific vaccination can elicit immune responses
      detectable in the peripheral blood of immunized patients. These assays, however,
      have been faulted by their requirement for in vitro expansion of T cells
      (limiting dilution or in vitro sensitization) or for limited sensitivity
      (ELISPOT). More recently, the use of soluble HLA/peptide complex tetramers,
      intracellular fluorescence-activated cell sorting (FACS) analysis, and real-time
      polymerase chain reaction (PCR) has been proposed for the monitoring of vaccine
      trials. These methods have the appeal of allowing direct enumeration of T cells
      specific for a particular epitope within relevant samples such as peripheral
      blood lymphocytes, lymph nodes, and tumors. We are evaluating whether utilizing a
      combination of HLA/peptide tetramer (tHLA) together with Taqman-based real-time
      reverse-transcription (RT)-PCR and intracellular FACS analysis could establish a
      direct and comprehensive strategy for the assessment of epitope-specific immune
      response in vivo. In conditions close to those of the tumor microenviroment or in
      peripheral blood lymphocytes, however, a different status of T cell activation
      can be expected due to a direct stimulation of T cells by tumor or antigen
      presenting cells. We observed that activated T cells can easily be detected in
      the peripheral blood of patients who have received MA-specific vaccines. However,
      when T cells are stimulated with their relevant epitope, a high level of T cell
      receptor downregulation occurs that does not allow identification of vaccine
      specific T cells directly with tHLA. Thus evaluation of epitope-specific T cells
      at the tumor site, where they might be exposed to stimulation by interaction with
      tumor cells and/or in bulk peripheral blood mononuclear cells, might be more
      efficiently analyzed with functional methods such as intracellular FACS and
      Taqman-based real time RT-PCR.

PMID- 10950151
TI  - Cancer cells engineered to secrete granulocyte-macrophage colony-stimulating
      factor using ex vivo gene transfer as vaccines for the treatment of genitourinary
      malignancies.
AB  - When irradiated and administered intradermally as vaccines, cancer cells
      engineered to secrete high levels of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) by gene transfer elicit potent anticancer immune responses in a
      variety of animal tumor models. Upon vaccination, antigens present in the cancer
      cells are phagocytosed and processed by skin dendritic cells. These dendritic
      cells then prime anticancer immune responses by presenting antigenic peptides to
      T cells. The immune responses generated are capable of eradicating small but
      lethal cancer cell inocula with minimal toxicity in preclinical animal tumor
      studies. To develop this vaccination strategy for the treatment of human
      genitourinary cancers, we have conducted phase I clinical trials using human
      genitourinary cancer cells as sources of cancer cell antigens. In the first human
      clinical trial of genetically engineered cancer cell vaccines, a phase I clinical
      trial of kidney cancer cell vaccines (n = 18), kidney cancer cells were removed
      at surgery, propagated briefly in vitro, and then genetically modified to secrete
      high levels of GM-CSF via ex vivo transduction with the retrovirus MFG-GM-CSF.
      After irradiation, the kidney cancer cells were administered as vaccines to 18
      patients with advanced kidney cancers. Vaccine treatment, which caused few side
      effects, nonetheless appeared to trigger anticancer immune responses manifest as
      conversion of delayed-type hypersensitivity (DTH) skin responses against
      irradiated autologous cancer cells after vaccination. Biopsies of vaccine sites
      yielded findings reminiscent of biopsies from preclinical animal model studies,
      with evidence of vaccine cell recruitment of dendritic cells, T cells, and
      eosinophils. One patient with measurable kidney cancer metastases treated at the
      highest vaccine dose level experienced a partial treatment response. The
      bioactivity of GM-CSF-secreting autologous cancer cell vaccines was confirmed in
      a phase I clinical trial for prostate cancer (n = 8). Vaccine cells were prepared
      from surgically harvested prostate tumors by ex vivo transduction with MFG-GM-CSF
      in a manner similar to that used for the kidney cancer trial. Vaccine treatment
      was well tolerated and associated with induction of anticancer immunity as
      assessed using DTH skin testing. In addition, new antiprostate cancer cell
      antibodies were detected in serum samples from treated men as a consequence of
      vaccination. These first clinical trials of GM-CSF-secreting cancer cell vaccines
      for the treatment of genitourinary cancers have demonstrated both safety and
      bioactivity, in that very few side effects have been seen and anticancer immune
      responses have been detected. Future clinical studies will be required to assess
      vaccine treatment efficacy, refine vaccination dose and schedule, define the
      appropriate clinical context for the use of such vaccines, and ascertain optimal
      combinations involving vaccines and other local or systemic anticancer
      treatments.

PMID- 10950152
TI  - Progress reports on immune gene therapy for stage IV renal cell cancer using
      lethally irradiated granulocyte-macrophage colony-stimulating factor-transduced
      autologous renal cancer cells.
AB  - There is no effective treatment for patients with stage IV renal cell cancer
      (RCC), although the introduction of new therapy is imminent. Cancer gene therapy
      is currently considered to be one of the most promising therapeutic modalities in
      the field of cancer treatment. Based on the results of animal studies,
      vaccination using autologous granulocyte-macrophage colony-stimulating factor
      transduced renal cancer cells appears promising. Before initiating a clinical
      study using an ex vivo gene-transduced autologous cell vaccine-based immunogene
      therapy for RCC in Japan, in 1992 we initially planned a Japanese version of a
      clinical protocol in collaboration with a US group. In 1993, the original
      protocol was refined. We performed five preclinical qualification studies using
      RCC nephrectomy specimens from patients in 1997, and the results showed that
      preparation of RCC cells for autologous vaccines at the Clinical Cell Technology
      Facility, Research Hospital of the Institute of Medical Science, University of
      Tokyo, was feasible. Subsequently in August 1998, the Ministry of Health and
      Welfare and the Ministry of Education, Science, Culture, and Sport approved our
      clinical protocol. We have recruited two patients with stage IV RCC to our study
      so far. Here we report the background to the initiation of cancer gene therapy in
      Japan.

PMID- 10950153
TI  - Development of a cancer vaccine: peptides, proteins, and DNA.
AB  - Genetic changes leading to protooncogene activation qualitatively and/or
      quantitatively alter their gene products and are exclusively or largely
      restricted to transforming cells and their precursors. The overexpression of HER2
      is among those changes and is often detected in adenocarcinomas such as breast,
      ovarian, lung, and gastric cancer. This provides a rationale for exploring the
      possibility that HER2 is a target of host immune responses against cancer cells.
      We have recently demonstrated that HER2 can be a target for tumor-rejecting
      immune responses against syngeneic murine HER2+ tumor cells. We defined two
      different peptides, HER2p63-71 and HER2p780-788, with a Kd anchor motif that can
      induce CD8+ cytotoxic T lymphocytes (CTLs). The growth of HER2+ syngeneic tumors
      was suppressed in mice immunized with HER2p63-71 or p780-788. Since murine Kd and
      human HLA-A24 share a similar anchor motif for peptides, HER2p63 71 and HER2p780
      788 were examined for induction of CTLs in HLA-A24+ individuals. CD8+ CTL clones
      specific for these peptides were established and they lysed HER2+ tumor cells in
      a human leukocyte antigen (HLA)-A24-restricted manner. To elicit specific CD8+ T
      cell immune responses against cancer, the development of efficient devices to
      deliver tumor antigen peptides to the major histocompatibility complex (MHC)
      class I pathway constitutes a central issue. We have developed a novel formula of
      hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein
      containing an epitope peptide to the MHC class I pathway. We designed a simple
      protein delivery system: cholesteryl group-bearing polysaccharides, mannan or
      pullulan (CHM or CHP, respectively), complexed with the truncated HER2 protein
      containing the 147 N-terminal amino acids. These complexes were able to induce
      CD8+ CTLs against HER2+ tumors. CTLs were MHC class I restricted and specifically
      recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen.
      The complete rejection of tumors also occurred when CHM-HER2 was applied early
      after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+
      T cells played a major role. The results suggest that this unique hydrophobized
      polysaccharide may help soluble proteins to induce cellular immunity. Such a
      novel vaccine may be of potential benefit in cancer prevention and cancer
      therapy.

PMID- 10950154
TI  - Use of major histocompatibility complex class I tetramers to monitor tumor
      specific cytotoxic T lymphocyte response in melanoma patients.
AB  - There is now considerable evidence that human tumors often express antigens that
      render them susceptible to lysis by cytotoxic T lymphocytes (CTLs). These
      findings have raised hope for the development of cancer vaccines to trigger a
      tumor-specific immune response in cancer patients. To optimize the immunogenicity
      of cancer vaccines, it is important to improve the monitoring of the immune
      response. The use of tetrameric soluble major histocompatibility complex (MHC)
      class I/peptide complexes ("tetramers") to identify tumor-specific CTLs has shown
      that these novel reagents allow rapid and accurate analysis of human CTL
      responses in cancer patients. We have used fluorescence-driven cell sorting to
      clone tumor-specific CTLs after staining with tetrameric MHC class I/peptide
      complexes. Analysis of melanoma-infiltrated lymph nodes revealed that strong CTL
      responses often occur in vivo, and that the reactive CTLs have substantial
      proliferative and tumoricidal potential.

PMID- 10950155
TI  - Human CD8 and CD4 T cell epitopes of epithelial cancer antigens.
AB  - Recent human tumor immunology research has identified several genes coding
      immunogenic peptides recognized by CD8 cytotoxic T lymphocytes (CTLs) in melanoma
      tumors. Very recently, CD4 T cell antigenic epitopes were also determined in
      certain melanoma tumors. The use of these peptides in conjunction with human
      immunotherapy could prove to be of great benefit. However, such peptides in
      clinically common tumors of epithelial cell origin, such as of the stomach,
      colon, lung, etc., have not yet been determined extensively. We describe for the
      first time an HLA-A31 (A*31012)-restricted natural antigenic peptide recognized
      by the CD8 CTL TcHST-2 of gastric signet ring cell carcinoma cell line HST-2. We
      also identified the HLA-DRB1*08032-restricted peptide recognized by the CD4 T
      cell line TcOSC-20 of squamous cell carcinoma OSC-20 derived from the oral
      cavity. The antigenic peptide of HST-2, designated F4.2, is composed of 10 amino
      acid residues with two anchor motif residues necessary for binding to HLA-A31
      molecules. The synthetic F4.2 peptide enhanced the reactivity of TcHST-2 against
      HST-2 cells. Furthermore, introduction of an expression minigene coding F4.2
      peptide to HLA-A31(+) cells conferred cytotoxic susceptibility to TcHST-2 on the
      cells. Some stomach cancer lines into which the HLA-A31 gene had been introduced,
      such as MKN28-A31-2, were lysed by TcHST-2, suggesting the presence of F4.2
      peptide in at least some HLA-A31(+) stomach cancers. Furthermore, F4.2 peptide
      induced an F4.2 peptide-specific CTL response in at least 30-40% of HLA-A31(+)
      peripheral blood lymphocytes from gastric cancer patients, suggesting that F4.2
      peptide could be used as a cancer vaccine for gastric tumors. The natural
      antigenic peptide of OSC-20 was also determined using acid extraction and
      biochemical separation and by mass spectrometry. Consequently, OSC-20 peptide was
      designated as the 6-1-5 peptide, an HLA-DRB1*08032-restricted 16-mer peptide with
      two possible anchor motifs. It has an amino acid sequence identical to that of
      human alpha-enolase, suggesting that it was derived from the processed parental
      alpha-enolase protein. We are presently attempting to determine the genes that
      code tumor rejection antigens recognized by HLA-A24- and A26-restricted T cells,
      including those of pulmonary and pancreatic carcinomas. The search for these
      antigenic peptides may lead to the identification of immunogenic peptide antigens
      that would be suitable for clinical use in commonly occurring epithelial cancers.

PMID- 10950156
TI  - Idiopathic hirsutism.
AB  - Hirsutism, the presence of terminal (coarse) hairs in females in a male-like
      pattern, affects between 5% and 10% of women. Of the sex steroids, androgens are
      the most important in determining the type and distribution of hairs over the
      human body. Under the influence of androgens hair follicles that are producing
      vellus-type hairs can be stimulated to begin producing terminal hairs (i.e.,
      terminalized). The activity of local 5alpha-reductase (5alpha-RA) determines to a
      great extent the production of dihydrotestosterone (DHT), and consequently the
      effect of androgens on hair follicles. While there are two distinct 5alpha-RA
      isoenzymes, type 1 and type 2, the activity of these in the facial or abdominal
      skin of hirsute women remains to be determined. Although the definition of
      idiopathic hirsutism (IH) has been an evolving process, the diagnosis of IH
      should be applied only to hirsute patients with normal ovulatory function and
      circulating androgen levels. A history of regular menses is not sufficient to
      exclude ovulatory dysfunction, since up to 40% of eumenorrheic hirsute women are
      anovulatory. The diagnosis of IH, when strictly defined, will include less than
      20% of all hirsute women. The pathophysiology of IH is presumed to be a primary
      increase in skin 5alpha-RA activity, probably of both isoenzyme types, and
      possibly an alteration in androgen receptor function. Therapeutically, these
      patients respond to antiandrogen or 5alpha-RA inhibitor therapy. Pharmacological
      suppression of ovarian or adrenal androgen secretion may be of additional, albeit
      limited, benefit. New therapeutic strategies such as laser epilation or the use
      of new biological response modifiers may play an important role in offering a
      more effective means of treatment to remove unwanted hair. Further investigations
      into the genetic, molecular, and metabolic aspects of this disorder, including
      only well defined patients, are needed.

PMID- 10950157
TI  - Role of hormones in pilosebaceous unit development.
AB  - Androgens are required for sexual hair and sebaceous gland development. However,
      pilosebaceous unit (PSU) growth and differentiation require the interaction of
      androgen with numerous other biological factors. The pattern of PSU
      responsiveness to androgen is determined in the embryo. Hair follicle growth
      involves close reciprocal epithelial-stromal interactions that recapitulate
      ontogeny; these interactions are necessary for optimal hair growth in culture.
      Peroxisome proliferator-activated receptors (PPARs) and retinoids have recently
      been found to specifically affect sebaceous cell growth and differentiation. Many
      other hormones such as GH, insulin-like growth factors, insulin, glucocorticoids,
      estrogen, and thyroid hormone play important roles in PSU growth and development.
      The biological and endocrinological basis of PSU development and the hormonal
      treatment of the PSU disorders hirsutism, acne vulgaris, and pattern alopecia are
      reviewed. Improved understanding of the multiplicity of factors involved in
      normal PSU growth and differentiation will be necessary to provide optimal
      treatment approaches for these disorders.

PMID- 10950158
TI  - Regulation of osteoblast differentiation mediated by bone morphogenetic proteins,
      hedgehogs, and Cbfa1.
AB  - Osteoblasts arise from common progenitors with chondrocytes, muscle and
      adipocytes, and various hormones and local factors regulate their
      differentiation. We review here regulation of osteoblast differentiation mediated
      by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and
      the transcription factor, core-binding factor alpha-1 (Cbfa1). BMPs are the most
      potent regulators of osteoblast differentiation among the local factors. Sonic
      and Indian hedgehogs are involved in osteoblast differentiation by interacting
      with BMPs. Cbfa1, a member of the runt domain gene family, plays a major role in
      the processes of a determination of osteoblast cell lineage and maturation of
      osteoblasts. Cbfa1 is an essential transcription factor for osteoblast
      differentiation and bone formation, because Cbfa1-deficient mice completely
      lacked bone formation due to maturation arrest ofosteoblasts. Although the
      regulatory mechanism of Cbfa1 expression has not been fully clarified, BMPs are
      an important local factor that up-regulates Cbfa1 expression. Thus, the intimate
      interaction between local factors such as BMPs and hedgehogs and the
      transcription factor, Cbfa1, is important to osteoblast differentiation and bone
      formation.

PMID- 10950159
TI  - Neuroendocrine control of thymus physiology.
AB  - The thymus gland is a central lymphoid organ in which bone marrow-derived T cell
      precursors undergo differentiation, eventually leading to migration of positively
      selected thymocytes to the peripheral lymphoid organs. This differentiation
      occurs along with cell migration in the context of the thymic microenvironment,
      formed of epithelial cells, macrophages, dendritic cells, fibroblasts, and
      extracellular matrix components. Various interactions occurring between
      microenvironmental cells and differentiating thymocytes are under neuroendocrine
      control. In this review, we summarize data showing that thymus physiology is
      pleiotropically influenced by hormones and neuropeptides. These molecules
      modulate the expression of major histocompatibility complex gene products by
      microenvironmental cells and the extracellular matrix-mediated interactions,
      leading to enhanced thymocyte adhesion to thymic epithelial cells. Cytokine
      production and thymic endocrine function (herein exemplified by thymulin
      production) are also hormonally controlled, and, interestingly in this latter
      case, a bidirectional circuitry seems to exist since thymic-derived peptides also
      modulate hormonal production. In addition to their role in thymic cell
      proliferation and apoptosis, hormones and neuropeptides also modulate intrathymic
      T cell differentiation, influencing the generation of the T cell repertoire.
      Finally, neuroendocrine control of the thymus appears extremely complex, with
      possible influence of biological circuitry involving the intrathymic production
      of a variety of hormones and neuropeptides and the expression of their respective
      receptors by thymic cells.

PMID- 10950160
TI  - Citation for the 2000 Fred Conrad Koch Award of The Endocrine Society to Dr. C.
      Ronald Kahn.

PMID- 10950161
TI  - Citation for the 2000 Ernst Oppenheimer award of The Endocrine Society to Dr.
      Christopher K. Glass.

PMID- 10950162
TI  - Citation for the 2000 Robert H. Williams Distinguished Leadership Award of The
      Endocrine Society to Dr. William W. Chin.

PMID- 10950163
TI  - Citation for the 2000 Edwin B. Astwood Award Lecture of The Endocrine Society to
      Dr. Jeffrey M. Rosen.

PMID- 10950164
TI  - Citation for the 2000 Monsanto Clinical Investigator Award Lecture of The
      Endocrine Society to Dr. William F. Crowley.

PMID- 10950165
TI  - Citation for the 2000 Gerald D. Aurbach Award Lecture of The Endocrine Society to
      Dr. Marvin Gershengorn.

PMID- 10950166
TI  - Citation for the 2000 Sidney H. Ingbar Distinguished Service Award of The
      Endocrine Society to Dr. Frank Talamantes.

PMID- 10950167
TI  - Citation for the 2000 Roy O. Greep Award Lecture of The Endocrine Society to Dr.
      Christin Carter-Su.

PMID- 10950168
TI  - Citation for the 2000 Distinguished Educator Award of The Endocrine Society to
      Dr. Stanley Korenman.

PMID- 10950169
TI  - Citation for the 2000 Distinguished Physician Award of The Endocrine Society to
      Dr. Michael O. Thorner.

PMID- 10950170
TI  - Citation for the 2000 Richard E. Weitzman Award of The Endocrine Society to Dr.
      Teresa K. Woodruff.

PMID- 10950171
TI  - Identification of rat IL-1beta, IL-2, IFN-gamma and TNF-alpha in activated
      splenocytes by intracellular immunostaining.
AB  - We have developed a sensitive three-step indirect immunofluorescence method to
      identify individual rat cells that produce cytokines including IL-1beta, IL-2,
      IFN-gamma and TNF-alpha. Cultured rat splenocytes were polyclonally activated to
      cytokine synthesis by mitogens such as lipopolysaccharide or a combination of a
      protein kinase C activator (phorbol 12-myristate 13-acetate) and a calcium
      ionophore (ionomycin). Careful selection of either antigen affinity-purified
      polyclonal or monoclonal cytokine-detecting antibodies combined with gentle
      fixation and permeabilization of the cells enabled discrimination of cytokine
      producing cells based on distinct morphological staining criteria. Cells making
      IL-2, IFN-gamma and TNF-alpha could be identified by a characteristic,
      intracellular, rounded, juxtanuclear immunofluorescence signal. This staining
      pattern reflected the accumulation of the intracellularly processed cytokines in
      the Golgi organelle of producer cells. The staining of cells that synthesized IL
      1beta, which is not transported intracellularly via the endoplasmatic reticulum
      Golgi pathway, generated a different, but distinct and reproducible staining
      pattern, IL-1beta producing macrophages expressed intense nuclear
      immunofluorescence with additional reticular, cytoplasmic signals. Furthermore,
      the use of biologically neutralizing detecting antibodies against the cytokines
      under study prevented recognition of surface-stained target cells that had bound
      secreted cytokines by cytokine-specific receptors. This modified staining
      technology enabled analysis of the kinetic pattern and the frequency of cytokine
      producing cells in cultures of rat splenocytes after various modes of polyclonal
      activation.

PMID- 10950172
TI  - Detection of DNA in ancient bones using histochemical methods.
AB  - We describe histochemical techniques for detecting DNA within the osteocytic
      lacunae of ancient bones. The bones examined were fragments of femurs from two
      human individuals found in the Pompeian C. I. Polybius house and fragments of
      metacarpals from two horses (Equus sp.) found in the Pompeian "Casti Amanti"
      house. Both buildings were buried by the 79 A. D. Vesuvius eruption. Fragments of
      femurs from a modern horse, a modern swine and a modern amphibian also were
      studied as controls. Some bone sections were stained with two different DNA
      specific fluorochromes, 4'-'6-diamidino-2-phenylindole (DAPI) and chromomycin A3
      (CMA), while others were stained by the Feulgen reaction. All of the techniques
      gave a positive reaction within the osteocytic lacunae. Histological analysis of
      the undecalcified, ground and unstained sections agreed well with results of bone
      sections stained with either the fluorochromes or the Feulgen reaction. Bones
      showing good histology also were positive by our DNA-specific stain.
      Histochemical and histological analyses correlated well with the success of DNA
      extraction and amplification. Using conventional DNA-specific histochemical
      techniques in conjunction with histological analysis can be useful in the study
      of DNA extracted from ancient bone remains while reducing both the amount of time
      and cost.

PMID- 10950173
TI  - Optimization of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester for
      labeling human intervertebral disc cells in vitro.
AB  - We have assessed the utility of an intracellular fluorochrome, 5-(and-6)
      carboxyfluorescein diacetate succinimidyl ester (CFSE), as a tracking label for
      human intervertebral disc cells in vitro. Although 5 microM provides adequate
      intracellular labeling for whole cell fluorescent microscopic identification of
      labeled cells, 20 microM was preferable for immunocytochemical localization of
      paraffin embedded labeled cells. Electron dense vesicles are seen at the
      ultrastructural level in labeled cells. Discrete vesicular labeling can also be
      observed in whole cell mounts viewed with fluorescence microscopy. Whole cells
      retain good label for 6 weeks. CFSE labeling is relatively easy, nontoxic to
      cells and nonradiocactive. Initial optimization of dose with specific cells types
      is recommended when confirmation of positive immunocytochemistry is needed for
      tissue engineering studies.

PMID- 10950174
TI  - Zirconyl hematoxylin: a new stain for acidic mucins.
AB  - Most stains for acidic mucins are time-consuming to prepare and have poor
      stability. Zirconyl hematoxylin is easily prepared and works for a year or more.
      It is made by adding 5 ml freshly-made 0.1% aqueous sodium iodate, 400 mg
      zirconyl chloride octahydrate, and 40 ml 25% aqueous glycerol, in that order, to
      100 mg of hematoxylin in 5 ml of absolute ethanol and stirring for 5 min. Stain
      10 min and do not "blue" the stain. Chlorazole black or kernechtrot and fast
      green are good counterstains. Zirconyl hematoxylin stains acidic mucins violet or
      red violet, regardless of how they are fixed. It stains the same mucins as alcian
      blue in mouse and sheep salivary glands. It shows goblet cells in mouse rectum as
      well as alcian blue. It stains the same stomach regions in a lizard as alcian
      blue. Like alcian blue and colloidal iron, zirconyl hematoxylin stains the mucin
      of cancerous prostate, but not normal prostate.

PMID- 10950175
TI  - Specific heterochromatic banding of metaphase chromosomes using nuclear yellow.
AB  - The bis-benzimidazole compound nuclear yellow (NY) belongs to the same chemical
      family as the DNA binding fluorochromes Hoechst 33258 and Hoechst 33342.
      Spectroscopic studies of NY alone and in the presence of calf thymus DNA show
      high DNA binding affinity and behavior similar to the Hoechst fluorochromes
      above. Mitotic metaphase chromosomes from Balb/c mice stained with NY show C
      banding and weak G/Q-banding, both of them disappearing after distamycin A (DA)
      or methyl green (MG) counterstaining. The same staining of human metaphase
      chromosomes from lymphocyte cultures, however, reveal only faint G/Q-banding (NY)
      and a characteristic DA-DAPI-like banding (NY-DA, NY-MG). Image analysis of NY
      stained human chromosomes, confirms that NY is suitable for studying
      polymorphisms affecting size in the pericentromeric heterochromatin of pairs 1, 9
      and 16, and shows significant enhancement of NY fluorescence induced by DA in DA
      DAPI heterochromatin. Our spectroscopic and cytological results show that NY,
      either alone or counterstained with DA or MG, can be used for DNA cytochemistry
      and chromosome banding. Possible mechanisms for the banding patterns induced by
      NY are discussed.

PMID- 10950176
TI  - Retroviral labeling is an appropriate marker for dividing cells.
AB  - 5-Bromo-2'-deoxyuridne (BrdU) and 3H-thymidine label mitotically active cells,
      but they do not adequately mark the progeny of dividing cells for long term
      study. An alternative method is to label cells using the replication-defective
      CXL retroviral vector, which carries the lacZ gene encoding beta-galactosidase;
      however, the ability of the CXL retroviral vector to pulse-label mitotically
      active cells selectively is not known. Cultures of proliferating muscle cells
      were simultaneously incubated with the CXL retrovirus and BrdU (10 microM) for 2
      hr. After removing the retrovirus containing medium, the cells were maintained
      for an additional 24 hr in vitro before they were stained to detect beta
      galactosidase and BrdU simultaneously. More than 95% of beta-galactosidase
      positive cells were also BrdU positive suggesting that the majority of beta
      galactosidase positive cells were in the S-phase of the cell cycle at the time of
      CXL retroviral administration. Therefore, the CXL retroviral vector is an
      appropriate pulse marker for dividing cells, and it is useful when it is
      desirable to know the fate of the progeny of a particular cell following a
      mitotic event.

PMID- 10950177
TI  - Alcian blue pyridine variant--a superior alternative to alcian blue 8GX: staining
      performance and stability.
AB  - We compared the staining performance, dye content, solubility, and visual
      absorption maximum of two batches of alcian blue pyridine variant and of five
      batches of alcian blue 8GX (C.I. 74240). Whenever possible, we also compared
      results to those obtained with the same dye batches produced at an earlier date
      to provide information concerning dye stability. Both alcian blue pyridine
      variant batches were of high dye content, stable, of satisfactory solubility, and
      performed well in both the routine Mowry mucin stain and in the critical
      electrolyte concentration (CEC) stain. Of the five alcian blue 8GX samples, some
      were also of appropriate dye content, were sufficiently stable, and gave good
      staining in the two procedures. Two batches, however, were unstable, and three
      batches were unsatisfactory in staining performance and solubility in the CEC
      stain. Consequently alcian blue pyridine variant is a superior substitute for
      alcian blue 8GX.

PMID- 10950178
TI  - Grouping by plasmid profiles of atypical Aeromonas salmonicida isolated from
      fish, with special reference to salmonid fish.
AB  - Plasmid profile analyses were performed for 113 strains of atypical Aeromonas
      salmonicida and the reference strain A. salmonicida subsp. salmonicida ATCC
      14174. The atypical A. salmonicida strains comprised 98 strains obtained from
      fish originating from 54 farms and 2 lakes in Norway, 10 strains from Canada (2),
      Denmark (2), Finland (1), Iceland (1) and Sweden (4), the reference strains NCMB
      1109 and ATCC 15711 (Haemophilus piscium) of A. salmonicida subsp. achromogenes,
      and the type cultures A. salmonicida subsp. achromogenes NCMB 1110, A.
      salmonicida subsp. masoucida ATCC 27013 and A. salmonicida subsp. smithia CCM
      4103. A total of 95 strains of atypical A. salmonicida were separated into 7
      groups (I to VII) based on the plasmid profiles. Eighteen strains of atypical A.
      salmonicida had no common plasmid profile. The type strain NCMB 1110 and the
      reference strain NCMB 1109 were included in group IV, and the type strain ATCC
      27013 in group V, but the other reference and type strains had plasmid profiles
      different from all the other strains. An epidemiological link was documented
      between strains collected from different farms/localities in each of groups I,
      III, V and VII. Physiological and biochemical characterizations were performed
      for 93 of the strains to investigate phenotypic differences between the plasmid
      groups. Group VII strains and 3 strains with no common plasmid profile differed
      from the other groups in being catalase-negative. Differences in phenotypic
      characteristics were shown between the plasmid groups. However, significant
      variations in reactions for several phenotypic characteristics also occurred
      within each of the groups I to VII. The present study indicates that plasmid
      profiling may give useful epidemiological information during outbreaks of
      atypical A. salmonicida infections in fish. Additional comprehensive phenotypic
      characterisation is of limited value since the phenotypic characteristics in each
      plasmid group are not uniform.

PMID- 10950179
TI  - Effect of Flavobacterium psychrophilum strains and their metabolites on the
      oxidative activity of rainbow trout oncorhynchus mykiss phagocytes.
AB  - The oxidative activity of rainbow trout phagocytes was studied using a
      chemiluminescence technique using 12 different Flavobacterium psychrophilum
      strains and their metabolites. Phagocytes were obtained from the head kidney of
      rainbow trout Oncorhynchus mykiss. The addition of viable F. psychrophilum or
      their metabolites to the phagocytes resulted in an immediate chemiluminescence
      response. The stimulating effects of both the F. psychrophilum and their
      metabolites on the phagocytes were found to be heat stable. No significant
      differences in stimulation capacity were found between the strains tested. To
      investigate the nature of the stimulating agent, both the bacteria and the
      supernatant were treated with either sodium metaperiodate or polymyxin B. Adding
      polymyxin B to the bacterial cells and supernatant did not change the
      chemiluminescence pattern, suggesting that the capacity of F. psychrophilum to
      stimulate the phagocytes probably is not due to lipopolysaccharides (LPS).
      However, following incubation of the bacteria and their metabolites with sodium
      metaperiodate, the capacity to stimulate phagocytes was significantly impaired.
      This suggests that a carbohydrate component most likely plays an important role
      in the ability of F. psychrophilum to stimulate phagocytes. Opsonisation of the
      bacteria with native trout serum or with rabbit anti-F. psychrophilum serum
      resulted in an additional chemiluminescence peak which was significantly higher
      than the first peak. This extra peak disappeared following heat treatment of the
      trout serum and the rabbit anti-F. psychrophilum serum, pointing towards the
      involvement of heat labile complement in opsonisation.

PMID- 10950180
TI  - Method for flow cytometric monitoring of Renibacterium salmoninarum inactivation.
AB  - The slow growth of Renibacterium salmoninarum limits the usefulness of culture as
      a research tool. Development of a 2-color flow cytometric assay to quantify the
      proportions of live and dead R. salmoninarum in a test population is described.
      Bacteria were simultaneously stained with fluorescein isothiocyanate-conjugated
      immunoglobulin and exposed to the exclusion dye propidium iodide. Propidium
      iodide red fluorescence profiles of control groups of untreated and killed R.
      salmoninarum were compared with those for bacteria exposed to chlorine. Bacterial
      inactivation was based on mean red fluorescence intensity, and analyzed by high
      red fluorescence intensity (HRFI) and curve subtraction (CS) analyses. When the
      concentration of R. salmoninarum was 8.65 x 10(6) bacteria ml(-1) and the
      bacteria exposed to chlorine at 1 mg l(-1) for periods from 1 to 20 min (high-Rs
      assessment), the mean red fluorescence intensity of the profile for each chlorine
      exposure group was higher than that for the untreated control (p < 0.0001). When
      the concentration of R. salmoninarum was reduced to 1.76 x 10(6) bacteria ml(-1)
      and exposed to 0.8 mg l(-1) free chlorine level for periods from 20 s to 5 min
      (reduced-Rs assessment), the mean red fluorescence intensities of the exposure
      groups were higher than that for the untreated control only when the R.
      salmoninarum was exposed to chlorine for at least 1 min (p < or = 0.01). On the
      basis of red fluorescence intensity, the proportion of dead cells generally
      increased with the duration of chlorine exposure. Whereas the rates of
      inactivation derived from the HRFI and CS analyses did not correlate with the
      duration of exposure in the high-Rs assessment (r2 < or = 0.27), there was a
      correlation between these estimates and the duration of exposure in the reduced
      Rs assessment (r2 > or = 0.92). Because of the rapid loss of culturable R.
      salmoninarum in both assessments following chlorine exposure, neither the
      duration of exposure nor the inactivation estimates correlated with
      bacteriological culture (r2 < or = 0.22). In both assessments, there was a
      correlation between the estimates of inactivation based upon HRFI and CS analyses
      (r2 > 0.99). These results suggest that flow cytometry can be used as a
      supplementary or alternative method to bacteriological culture for monitoring the
      inactivation of R. salmoninarum.

PMID- 10950181
TI  - In vitro cultivation of Trypanoplasma borreli (protozoa: kinetoplastida), a
      parasite from the blood of common carp Cyprinus carpio.
AB  - An in vitro culture system was developed for Trypanoplasma borreli, a pathogenic
      flagellate from the blood of European cyprinids. Trypanoplasms multiplied rapidly
      in a mixture of Hanks' balanced salt solution (HBSS, 45%), L15 (22.5%), Earle's
      minimum essential medium (MEM, 22.5%) and 10% distilled water, which was
      supplemented with 5 to 10% heat-inactivated pooled carp serum. In medium
      supplemented with fetal bovine serum, multiplication of T. borreli seemed to be
      inhibited. Cultures initiated with less than 100 000 T. borreli per ml culture
      medium did not survive, and a substantial multiplication of trypanoplasms was
      found at inocula beginning with 630 000 flagellates ml(-1). Trypanoplasms
      multiplied at 15, 20 and 25 degrees C. In cultures incubated at 4 degrees C the
      trypanoplasms remained viable but the number of flagellates did not increase.
      Trypanoplasms from in vitro cultures retained their infectivity for carp for at
      least 90 d (5 passages). The trypanoplasms survived in culture over a period of
      up to 5 mo (10 passages). The established culture system allows the propagation
      of high numbers of fish-infective trypanoplasms, which are required to study
      parasite-host relationships in carp.

PMID- 10950182
TI  - Flow cytometric analysis of proliferative responses of carp Cyprinus carpio
      peripheral blood leukocytes to mitogens and to the hemoflagellate Trypanoplasma
      borreli.
AB  - The activation of carp peripheral blood leukocytes (PBL) was analysed
      radiometrically and by means of flow cytometry (FCM) in order to compare the
      results obtained with both methods. The qualitative and quantitative FCM analyses
      of cellular morphology and viability resulted in a further characterisation of
      proliferative responses of carp PBL to Trypanoplasma borreli in vivo and in
      vitro. The lymphocyte population of PBL from T. borreli-infected carp exhibited a
      marked shift in forward scattered light (FSC; cell size). When PBL from healthy
      carp were stimulated with mitogens in vitro, a lymphoid population with increased
      FSC profiles was also observed. The number of these cells coincided to ratios of
      3H-thymidine incorporation, recorded from corresponding cultures. Thus, it was
      concluded that the increase in size of stimulated lymphocytes could be due to
      blastogenic transformation. The advantage of the FCM procedure is that activation
      and proliferation of carp lymphocytes can be monitored without labelling the
      cells. Cocultures of mitogen-stimulated carp PBL and T. borreli revealed the
      ability of the parasite to suppress lymphocyte proliferation in vitro.

PMID- 10950183
TI  - Tumor formation on the coral Montipora informis.
AB  - A high incidence of tumors (i.e., abnormal skeletal growth) was observed on
      Montipora informis Bernard, 1897 (Acroporidae) coral colonies on the shallow reef
      flat of Sesoko Island, Okinawa, Japan. Tumors were recognized as slightly
      hemispherical protuberances and were characterized by fewer numbers of polyps per
      surface area, fewer zooxanthellae per polyp, and finer skeletal structures than
      normal. In addition, fecundity was significantly reduced in tumored areas. Tumor
      formation appeared localized, stable and non-epidemic. During the summer of 1998,
      coincident with the global coral bleaching event, tumored tissue suffered higher
      mortality than normal tissue. The mechanism triggering tumor formation remains
      unknown.

PMID- 10950184
TI  - Selection of brood stock candidates of barfin flounder using an ELISA system with
      recombinant protein of barfin flounder nervous necrosis virus.
AB  - Barfin flounder nervous necrosis virus (BFNNV), the causative agent of viral
      nervous necrosis (VNN) of barfin flounder, is vertically transmitted from
      spawners to larvae. In the present study, an ELISA with a recombinant protein of
      BFNNV was performed for the detection of antibodies against BFNNV and applied for
      the selection of brood fish in order to prevent viral vertical transmissions.
      Brood stocks were divided into 4 groups based on ELISA antibody titers (< or =
      10, 20, 40 and >40), and the BFNNV status of the brood stocks was determined by
      PCR. BFNNV was detected from the brood fish in the group with an antibody titer
      of >40 but not from those with titers < or = 10, 20 and 40. The offspring
      obtained from PCR-negative brood fish pairs in each group of ELISA antibody
      titers were subsequently reared for observation of VNN occurrence. VNN occurred
      in juveniles from 2 of 9 pairs of spawners with an antibody titer > or = 40, but
      did not occur in spawners with an antibody titer of < or = 10. Therefore, it was
      concluded that selection of brood fish using both the PCR test and ELISA antibody
      titers could help prevent vertical transmission of BFNNV in larval production of
      barfin flounder.

PMID- 10950185
TI  - Susceptibility of juvenile Atlantic cod Gadus morhua to viral haemorrhagic
      septicaemia virus isolated from wild-caught Atlantic cod.
AB  - A European strain of viral haemorrhagic septicaemia virus (VHSV) isolated from
      wild-caught cod Gadus morhua (H16/7/95) was shown to cause clinical disease and
      mortality in excess of 80% in juvenile Atlantic cod when administered by the
      intra-peritoneal (i.p.) route. No virus was recovered from cod cohabiting with
      experimentally infected fish at a ratio of 1:1, and no VHSV-associated mortality
      was demonstrated following immersion infection. External signs of disease in cod
      were the presence of exophthalmia and ascites. Virus was identified as VHSV by
      enzyme-linked immunosorbent assay (ELISA) and was recovered from both brain and
      organ pools (kidney, liver and spleen) of 100% of i.p. infected cod mortalities.
      Virus was also detected using an indirect immunofluorescence test on tissue
      imprints of kidney, liver, spleen and brain taken from moribund fish. The fact
      that cod were not susceptible to VHSV following waterborne exposure raises
      important questions surrounding the propagation, maintenance and impact of a
      naturally occurring reservoir of virus in the marine environment.

PMID- 10950186
TI  - Isolation and identification of Viral Haemorrhagic Septicaemia (VHS) viruses from
      cod Gadus morhua with the ulcus syndrome and from haddock Melanogrammus
      aeglefinus having skin haemorrhages in the North Sea.
AB  - During fish disease surveys for marine rhabdoviruses in 1993 and 1995, the cod
      ulcus syndrome was seen widely in all ages of cod, especially the 2 to 5+ year
      classes. Viral Haemorrhagic Septicaemia Virus (VHSV) was isolated from a small
      proportion of the lesion-positive fish and these isolates were identified by
      immunofluorescence or ELISA. A serendipitous observation of dermal petechiae on
      haddock was made. VHSV was isolated from this lesion for the first time
      indicating a new host species for VHSV.

PMID- 10950187
TI  - Hepatic lesions in a redstriped rockfish (Sebastes proriger) suggestive of a
      herpesvirus infection.
AB  - Unusual lesions were observed in a redstriped rockfish (Sebastes proriger)
      collected during a survey of marine fishes off the coast of British Columbia,
      Canada. This particular fish exhibited prominent hepatomegaly, with large,
      coalescing, multiple hemorrhages. The affected liver exhibited remarkable
      histological changes that, taken together, strongly suggested infection by a
      virus of the herpesvirus group. Multiple, multinucleated giant cells or syncytia
      of hepatocytes occurred throughout the liver and were associated with massive,
      coalescing areas of coagulation necrosis, edema, congestion and cavernous
      hemorrhages (peliosis hepatis) with thrombosis. In addition, the liver showed
      multifocal inflammation, characterized by perivascular and peribiliary cuffing of
      mononuclear inflammatory cells. High magnification of the syncytia revealed that
      the nuclei were pleomorphic, hyperchromatic, and typically contained eosinophilic
      to densely amphophilic inclusion bodies of varying size, closely resembling
      Cowdry Type A inclusions. These inclusions stained red to purple in Feulgen's
      stain, indicating presence of DNA. Electron-lucent spheres (approximately 100 nm
      diameter) were observed within hepatocyte nuclei by transmission electron
      microscopy, suggestive of herpesvirus capsids. To our knowledge, this is the
      first report of a putative or confirmed herpesvirus infection in any rockfish of
      the genus Sebastes.

PMID- 10950188
TI  - Effect of lysozyme or modified lysozyme fragments on DNA and RNA synthesis and
      membrane permeability of Escherichia coli.
AB  - Previously we have shown that chicken egg white lysozyme, an efficient
      bactericidal agent, affects both gram-positive and gram-negative bacteria
      independently of its muramidase activity. More recently we reported that the
      digestion of lysozyme by clostripain yielded a pentadecapeptide, IVSDGNGMNAWVAWR
      (amino acid 98-112 of chicken egg white lysozyme), with moderate bactericidal
      activity but without muramidase activity. On the basis of this amino acid
      sequence three polypeptides, in which asparagine 106 was replaced by arginine
      (IVSDGNGMRAWVAWR, RAWVAWR, RWVAWR), were synthesized which showed to be strongly
      bactericidal. To elucidate the mechanisms of action of lysozyme and of the
      modified antimicrobial polypeptides Escherichia coli strain ML-35p was used. It
      is an ideal organism to study the outer and the inner membrane permeabilization
      since it is cryptic for periplasmic beta-lactamase and cytoplasmic beta
      galactosidase unless the outer or inner membrane becomes damaged. For the first
      time we present evidence that lysozyme inhibits DNA and RNA synthesis and in
      contrast to the present view is able to damage the outer membrane of Escherichia
      coli. Blockage of macromolecular synthesis, outer membrane damage and inner
      membrane permeabilization bring about bacterial death. Ultrastructural studies
      indicate that lysozyme does not affect bacterial morphology but impairs stability
      of the organism. The bactericidal polypeptides derived from lysozyme block at
      first the synthesis of DNA and RNA which is followed by an increase of the outer
      membrane permeabilization causing the bacterial death. Inner membrane
      permeabilization, caused by RAWVAWR and RWVAWR, follows after the blockage of
      macromolecular synthesis and outer membrane damage, indicating that inner
      membrane permeabilization is not the deadly event. Escherichia coli bacteria
      killed by the substituted bactericidal polypeptides appeared, by electron
      microscopy, with a condensed cytoplasm and undulated bacterial membrane. So the
      action of lysozyme and its derived peptides is not identical.

PMID- 10950189
TI  - Design and application of a rapid screening technique for isolation of selenite
      reduction-deficient mutants of Shewanella putrefaciens.
AB  - A rapid screening technique for isolation of selenite (Se(IV)) reduction
      deficient (Ser) mutants was developed and used to identify four Ser mutants of
      Shewanella putrefaciens. Two Ser mutants were unable to grow anaerobically on
      fumarate, nitrate or nitrite. Two other Ser mutants were unable to grow
      anaerobically on all compounds tested as sole terminal electron acceptor.
      Previously isolated Mn(IV) reduction-deficient mutants displayed Ser-positive
      phenotypes and reduced Se(IV) at wild-type rates, while two of nine Fe(III)
      reduction-deficient mutants displayed Ser-negative phenotypes and reduced Se(IV)
      at low rates. This study provides the first reported method for isolation of Ser
      mutants and demonstrates that Se(IV) reduction by S. putrefaciens is respiratory
      chain-linked.

PMID- 10950190
TI  - Fe(III) reduction activity and cytochrome content of Shewanella putrefaciens
      grown on ten compounds as sole terminal electron acceptor.
AB  - Shewanella putrefaciens was grown on a series of ten alternate compounds as sole
      terminal electron acceptor. Each cell type was analyzed for Fe(III) reduction
      activity, absorbance maxima in reduced-minus-oxidized difference spectra and heme
      containing protein content. High-rate Fe(III) reduction activity, pronounced
      difference maxima at 521 and 551 nm and a predominant 29.3 kDa heme-containing
      protein expressed by cells grown on Fe(III), Mn(IV), U(VI), SO3(2-) and S2O3(2-),
      but not by cells grown on O2, NO3, NO2-, TMAO or fumarate. These results suggest
      that microbial Fe(III) reduction activity is enhanced by anaerobic growth on
      metals and sulfur compounds, yet is limited under all other terminal electron
      accepting conditions.

PMID- 10950191
TI  - Purification and characterization of lipase from psychrophilic Acinetobacter
      calcoaceticus LP009.
AB  - A lipase-producing bacterium, Acinetobacter calcoacetius LP009, was isolated from
      raw milk. The optimum conditions for growth and lipase production by A.
      calcoaceticus LP009 were 15 degrees C with shaking at 200 rpm in LB supplemented
      with 1.0% (v/v) Tween 80. The crude lipase was purified to homogeneous state by
      ultrafiltration and gel filtration chromatography on Sephadex G-100. Its
      molecular weight determined by SDS-PAGE was 23 kDa and it exhibited maximum
      activity at pH 7.0 and 50 degrees C. It was stable over the pH range of 4.0 to
      8.0 and at temperatures lower than 45 degrees C. It was a metalloenzyme that is
      positionally non-specific and had the ability to improve fat hydrolysis in
      soybean meal and in premixed animals feed.

PMID- 10950192
TI  - Deoxyribonuclease activities in Lactobacillus delbrueckii.
AB  - DNase activity was examined in the extracellular and subcellular fractions of six
      non-transformable strains belonging to Lactobacillus delbrueckii subsp. lactis
      (L. lactis) and Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) and
      compared with the activity present in Lactobacillus johnsonii NCK 65, a
      transformable strain of Lactobacillus. In the extracellular fraction of the L.
      delbrueckii strains, a common protein band of 36 kDa was detected, while a band
      of 29 kDa was found in the same fraction of L. johnsonii. No nuclease activity
      was detected in the cytoplasmic fraction of this strain, indicating that the
      localization of the DNase activity could be a key factor in the uptake of foreign
      DNA.

PMID- 10950193
TI  - The development of fungi as affected by pH and type of soil, in relation to the
      occurrence of bacteria and soil fungistatic activity.
AB  - A study was made on the effect of liming (Ca(OH)2) on the numbers of colony
      forming units (CFU) and the biomass of fungi in loamy sand (ls) and a loose sandy
      soil (lss) during 90 days under laboratory conditions. Liming inhibited the
      growth of fungi more strongly in the lighter soil. Raising the pH of lss from its
      native 4.5 to 7.0 and 9.0 decreased mean fungal CFU numbers by 50%, and their
      biomass by 42% and 68%, respectively, in comparison with control unlimed samples.
      Also in ls with its native pH of 7.7, when alkalinised to 9.0 and 11.0 the fungal
      CFU numbers were smaller than in the control by 25% and 50%, respectively, and
      the fungal biomass decreased by 40% and 56%, respectively. Although in a parallel
      research alkalinisation has been shown to stimulate bacterial growth very
      strongly, especially in lss, the total microbial biomass (fungal + bacterial)
      declined by an average of 30% (pH 9.0) and 40% (pH 11.0) in limed ls, and by 35%
      (pH 7.0) and as much as 50% (pH 9.0) in lss, in comparison with the control.

PMID- 10950194
TI  - Effect of associative bacteria on element composition of barley seedlings grown
      in solution culture at toxic cadmium concentrations.
AB  - The response of barley seedlings to inoculation with associative rhizobacteria
      Azospirillum lipoferum 137, Arthrobacter mysorens 7, Agrobacterium radiobacter 10
      and Flavobacterium sp. L30 was studied in hydroponic and quartz sand cultures in
      the presence of 50 microM CdCl2. Cadmium caused severe inhibition in the growth
      and uptake of nutrient elements by the plants. Inoculation with the bacteria
      slightly stimulated root length and biomass of hydroponically grown Cd-treated
      seedlings. The bacteria increased the content of nutrients such as P, Mg, Ca, Fe,
      Mn and Na in roots and or shoots of the plants grown in the absence of Cd.
      Positive changes in the element composition caused by the bacteria were less
      pronounced in Cd-treated plants, whereas the total amount of nutrients taken by
      the inoculated plants was generally increased significantly. The content of Cd in
      the inoculated plants was unchanged, except increased in roots upon addition of
      A. lipoferum 137. Inoculation did not affect the activity of peroxidase, alpha
      mannosidase, phosphodiesterae, alpha-galactosidase, and concentration of
      sulfhydryl compounds used as biochemical markers of stress in plant roots. The
      results showed that associative bacteria were capable of decreasing partially the
      toxicity of Cd for the barley plants through the improvement in uptake of
      nutrient elements.

PMID- 10950196
TI  - Studies on Alternaria sesami pathogenic to sesame.
AB  - Influence of pH on the growth of Alternaria sesami, its nutritional requirements
      and its ability to produce phytotoxic and antibacterial metabolites were tested.
      The isolate was cultured on Czapek-Dox broth and the culture filtrates were
      screened for phytotoxicity against seeds and seedlings of sesame. Chloroform
      extracts of the fungus exhibited antibacterial activity. Analysis of the culture
      filtrates for identifying toxins using chromatographic techniques revealed the
      presence of tenuazonic acid.

PMID- 10950195
TI  - Indole acetic acid production by a Rhizobium species from root nodules of a
      leguminous shrub, Cajanus cajan.
AB  - A Rhizobium sp. isolated from the root nodules of a leguminous pulse-yielding
      shrub, Cajanus cajan, was found to produce high amounts (99.7 microg/ml) of
      indole acetic acid (IAA) during growth in basal medium supplemented with L
      tryptophan. The Rhizobium sp. was a fast growing species which reached its
      stationary phase at 28 h. The IAA production could be increased upto 653.3% over
      control by supplementing the carbon-free incubation medium with glucose (5 g/l),
      NiCl2 (10 microg/ml) and glutamic acid (0.5 g/l). The possible role of rhizobial
      IAA on the rhizobia-legume symbiosis is discussed.

PMID- 10950197
TI  - Physiological and antagonistic potential of actinomycetes from loquat
      rhizosphere.
AB  - The microflora of Eriobotrya japonica (loquat) was studied by the serial
      dilutions-spread plate method. A variety of bacteria, fungi and actinomycetes was
      detected. The genus Steptomyces dominated in the population (83%). A great
      species diversity was found among Streptomycetes. Some of the actinomycetes
      possessed antibacterial activity (47%), others produced different exo-enzymes.

PMID- 10950198
TI  - Organizational cynicism: bases and consequences.
AB  - Organizational cynicism is the belief that an organization lacks integrity,
      which, when coupled with a powerful negative emotional reaction, leads to
      disparaging and critical behavior. In this article, the author attempts to
      theoretically clarify the process by which five forms of cynicism develop in the
      workplace and to empirically relate them to affective outcomes. Societal,
      employee, and organizational change cynicisms may be attributed to psychological
      contract violations; work cynicism may be related to burnout; and person-role
      conflict and personality cynicism may be related to innate hostility.
      Empirically, personality cynicism emerged as the strongest predictor of
      organizational cynicism, adversely affecting all of the criteria. Other forms of
      cynicism had more selective effects. Organizational change cynicism induced job
      dissatisfaction and alienation, and employee cynicism affected organizational
      commitment. Societal cynicism actually increased both job satisfaction and
      commitment. Both personality and work cynicisms were related to organizational
      citizenship indirectly, through alienation. Theoretical and practical
      implications are discussed.

PMID- 10950199
TI  - The understanding of sadness, guilt, and shame in 5-, 7-, and 9-year-old
      children.
AB  - Children's understanding of sadness and guilt and of guilt and shame were
      examined in two separate studies, each involving a total of 60 Italian children
      aged 5-6, 7-8, and 9-10 years. For each emotion, the children were individually
      interviewed; they were asked to describe antecedents, thoughts characterizing the
      emotion that was the subject of the interview, and the action tendencies a person
      might use in response to the emotion. The children were also asked if, and if so,
      how, the presence of a parent might affect the emotion, and how they would cope
      with the situation. Results showed that at all the ages considered in this study,
      the children knew about the three emotions, although there were some age
      differences related to the depth of their understanding. Such data show that
      children's understanding of social emotions occurs earlier than claimed in
      previous studies that have focused mainly on antecedents.

PMID- 10950200
TI  - Context effects and the (mal)adaptive nature of guilt and shame in children.
AB  - Symptoms of internalization were examined in relation to children's self-reports
      of three emotions in situations that were either ambiguous or unambiguous as to
      the child's responsibility for various standard violations. Children ranging in
      age from 6 to 13 years were drawn from elementary schools (61 boys, 79 girls,
      mean age = 8.7) and from a community mental health center (23 boys, 18 girls,
      mean age = 8.5) to which they had been referred for problems related to
      internalization or externalization. Shame proneness was consistently linked to
      internalizing symptoms across contexts. Guilt proneness, in response to ambiguous
      scenarios, was also associated with internalization, whereas pride responses were
      unrelated to symptoms. Few age- or gender-related differences were found. The
      results cast doubt on notions that self-conscious emotions, such as guilt, are
      necessarily adaptive or maladaptive. Systematic research is needed to understand
      which features of any emotion contribute to children's psychological adjustment.

PMID- 10950201
TI  - The quality of experience in adolescents' daily lives: developmental
      perspectives.
AB  - The authors analyzed the pattern of experience fluctuation in adolescents' daily
      activities. Italian high school students (N = 120; 16-20 years of age) were
      tested with the experience sampling method, a technique based on on-line sampling
      of daily life and experience. A total of 4,794 forms were gathered and analyzed
      by means of a model for the study of experience fluctuations. Among daily
      activities, studying at home, doing classwork, watching television, and having
      structured leisure were selected as the focus of analysis on the basis of their
      frequency and meaning in the adolescents' lives. Results showed that (a) daily
      activities have unique experiential profiles, (b) engagement may be used as an
      index of long-term commitment to a given activity, (c) studying at home and doing
      classwork share this basic component and can foster behavioral development, (d)
      structured leisure can play an edifying role at the short-term level for a
      socially integrated transition to adulthood, and (e) watching television is
      associated with lack of goals and engagement and is a source of apathy. The
      results (a) shed light on the role of daily life experience in shaping individual
      development and (b) provide suggestions for educational and psychosocial
      intervention in adolescence.

PMID- 10950202
TI  - Relative influence of composition and viscosity of acrylic bone cement on its
      apparent fracture toughness.
AB  - The composition and viscosity of an acrylic bone cement have both been identified
      in the literature as being parameters that affect the mechanical properties of
      the material and, by extension, the in vivo longevity of cemented arthroplasties.
      The objective of the present study was to determine the relative influence of
      these parameters on a key cement mechanical property; namely, its fracture
      toughness. Two sets of cements were selected purposefully to allow the study
      objective to be achieved. Thus, one set comprised two cements with very similar
      compositions but very different viscosities (Cemex RX, a medium-viscosity brand,
      and Cemex Isoplastic, a high-viscosity brand) while the other set comprised two
      cements with similar viscosities but with many differences in composition (Cemex
      Isoplastic and CMW 1). Values of the fracture toughness (as determined using
      chevron-notched short rod specimens) [K(ISR)] obtained for Cemex RX and Cemex
      Isoplastic were 1.83 +/- 0.12 and 1.85 +/- 0.12 MPa square root(m), respectively,
      with the difference not being statistically significant. The K(ISR) values
      obtained for Cemex Isoplastic and CMW 1 were 1.85 +/- 0.12 and 1.64 +/- 0.18 MPa
      square root(m), respectively, with the difference being statistically
      significant. Thus, the influence of cement composition on its K(ISR) is more
      marked relative to the influence of cement viscosity. Explanations of this
      finding are offered, together with comments on the implications of the results
      for the in vivo longevity of cemented arthroplasties.

PMID- 10950203
TI  - Sliding properties of plasma assisted CVD CNchi coatings for metal bioimplants.
AB  - Coatings of CNchi, have been prepared on the substrates of material Ti6Al4V, of
      which the human joint replacements are made. The deposition of the CNchi coating
      was carried out by PACVD method in apparatus with standard arrangement. The
      methane and nitrogen have been used as precursors for CNchi compound. The
      infrared absorption spectroscopy and Rutherford backscattering spectroscopy were
      applied on diagnostics of prepared CNchi layer. Beside carbon and nitrogen the
      hydrogen and oxygen were found in the coatings. The sliding tests were carried
      out with the samples. The counter parts were the cylinders made of the
      polyethylene of the same type as for big joint prostheses is used. The tests were
      carried out in the medium of physiological solution. The CNchi coatings perform
      well under the lower load of 25 and 50 N. When the load is increased to 100 N,
      the friction coefficient slowly increases, but measured values of mu are typical
      for boundary lubrication.

PMID- 10950204
TI  - High strength bioresorbable bone plates: preparation, mechanical properties and
      in vitro analysis.
AB  - Biodegradable bone plates were prepared as semi-interpenetrating networks (SIPN)
      of crosslinked polypropylene fumarate (PPF) within a host matrix of either
      poly(lactide-co-glycolide)-85:15 (PLGA) or poly(1-lactide-co-d,l-lactide)-70:30
      (PLA) using N-vinylpyrrolidone (NVP), ethylene glycol dimethacrylate (EGDMA), 2
      hydroxyethyl methacrylate (HEMA), and methyl methacrylate (MMA) as crosslinking
      agents. Hydroxyapatite (HAP), an inorganic filler material, was used to further
      augment mechanical strength. The control crosslinking agent (NVP) was replaced
      partially and totally with other crosslinking agents. The amount of crosslinking
      agent lost, the characterization change in the mechanical properties and the
      dimensional stability of the bone plates after in vitro treatment was calculated.
      The optimum crosslinking agent was selected on the basis of low in vitro release
      of NVP from SIPN matrix. Bone plates were then prepared using this crosslinking
      agent at 5 MPa pressure and at temperatures between 100-140 degrees C to
      determine if there was any augmentation of mechanical properties in the presence
      of the crosslinked network. In vitro analysis showed that 90% of the crosslinking
      agent was lost on plates using NVP as a crosslinking agent. This loss was reduced
      to 50% when NVP was partially replaced with EGDMA or MMA. EGDMA was determined to
      be superior because (1) its low release as a crosslinking agent, (2) flexural
      plate strength of 50-67 MPa, (3) flexural modulus of 7-13 GPa, and (4)
      manufacturability stiffness of 300-600 N/m. HAP-loading resulted in an additional
      increase in values of mechanical parameters. Substituting PLGA with PLA in the
      PPF-SIPN did not show any additional improvement of mechanical properties.

PMID- 10950205
TI  - Torquability of microcatheter guidewires: the resulting torsional moment.
AB  - Guidewires for microcatheters used for the subselective catheterization of small
      vessels must meet high quality requirements in regard to handling, steerability,
      radiopacity and physical properties. The aim of this paper is to classify one of
      the factors that determine the physical and mechanical parameters of a number of
      existing microcatheter guidewires. A torsion-testing equipment for guidewires was
      devised. Nitinol wires were tested and compared with the austenitic stainless
      steel variants. 13 different commercial wires were tested. Tensile strength,
      shear modulus and wire diameter are the determining factors of the torsional
      rigidity of guidewires. By interpreting the measured torsional momentums various
      statements concerning the torsional rigidity of different wires can be made. The
      properties of guidewires are characteristic features of a system and friction and
      flexible strength examinations have to be carried out to design new variants of
      wires to meet the requirements of interventional physicians.

PMID- 10950206
TI  - Fatigue data analysis of canine femurs under four-point bending.
AB  - When bone is subjected to fatigue loading, micro-cracks initiate and grow. This
      reduces the mechanical properties and quantitative relationships between
      stiffness loss and loading cycles may be derived. We developed the relationships
      between stiffness loss and loading cycles for whole canine femurs subjected to
      cyclic fatigue in four-point bending. The fatigue data from experiments followed
      Weibull statistics. When the stiffness loss is less than 15%, a linear
      relationship is best-fitted (R2 = 0.96, p < 0.0001) between the stiffness loss
      and loading cycles. However, when the stiffness loss is greater than 30%, a power
      law relationship is best-fitted (R2 = 0.97, p < 0.0001) between the stiffness
      loss and loading cycles. Thus, we conclude that the derived relationships between
      stiffness loss and loading cycles might be useful for the prediction of bone
      failure under cyclic bending subjected to an initial strain of 2700 microstrain.

PMID- 10950207
TI  - Private industry, academia team up on HIV vaccine.

PMID- 10950208
TI  - Screening for breast cancer.

PMID- 10950209
TI  - Meningococcal vaccine for college freshmen.

PMID- 10950210
TI  - Breast-feeding and infant oral health.

PMID- 10950211
TI  - Case report: neuropsychiatric complications of malaria infection.

PMID- 10950212
TI  - Lightening the lead load in children.
AB  - More than 4 percent of preschool-aged children in the United States have blood
      lead levels above 10 microg per dL (0.50 pmol per L), and these levels have been
      associated with a decline in IQ. The Centers for Disease Control and Prevention
      advocates the use of a screening questionnaire to identify lead exposure or
      toxicity in all children. Primary prevention through the removal of lead from
      gasoline and paint has led to a reduction of blood lead levels in children.
      Secondary prevention through paint hazard remediation is effective in homes that
      have a high lead burden. Children with lead levels of 45 to 69 microg per dL
      (2.15 to 3.35 pmol per L) should receive chelation therapy using succimer (DMSA)
      or edetate calcium disodium (CaNa2EDTA). Use of both CaNa2EDTA and dimercaprol
      (BAL in oil) is indicated in children with blood lead levels higher than 70
      microg per dL (3.40 micromol per L). Current treatment recommendations are based
      on the reduction of blood lead levels, which may not represent a significant
      overall reduction of the lead burden. Clinical trials of existing agents are
      needed to determine patient-oriented outcomes, such as the effect on IQ.

PMID- 10950213
TI  - Intra-articular hyaluronic acid injections for knee osteoarthritis.
AB  - Knee osteoarthritis is a common but often difficult problem to manage in primary
      care. Traditional nonsurgical management, consisting of lifestyle modification,
      physical therapy and pharmacologic therapy (e.g., analgesics, anti-inflammatory
      medications), is often ineffective or leaves residual symptoms.
      Viscosupplementation is a newly available option for patients with symptomatic
      knee osteoarthritis that involves a series of intra-articular injections of
      hyaluronic acid. The exact mechanism of action is unclear, although increasing
      the viscoelasticity of the synovial fluid appears to play a role. Clinical
      experience and studies of the two hyaluronic acid products available, hyaluronan
      and hylan G-F 20, are inconclusive but seem to indicate beneficial effects with
      minimal adverse reactions in a significant number of patients. The exact
      indications for viscosupplementation are still evolving, but it currently can be
      considered for use in patients who have significant residual symptoms despite
      traditional nonpharmacologic and pharmacologic treatments. In addition, patients
      who are intolerant of traditional treatments (e.g., gastrointestinal problems
      related to anti-inflammatory medications) can be considered for these injections.
      Family physicians with the ability to perform intra-articular knee injections
      should consider them an option in patients with symptomatic knee osteoarthritis.

PMID- 10950214
TI  - Assessing nicotine dependence.
AB  - Family physicians can assess the smoking behavior of their patients in a few
      minutes, using carefully chosen questions. The CAGE questionnaire for smoking
      (modified from the familiar CAGE questionnaire for alcoholism), the "four Cs"
      test and the Fagerstrom Test for Nicotine Dependence help make the diagnosis of
      nicotine dependence based on standard criteria. Additional questions can be used
      to determine the patient's readiness to change and the nature of the
      reinforcement the patient receives from smoking. These tools can assist family
      physicians in guiding patients to quit smoking-the single most important thing
      smokers can do to improve their health.

PMID- 10950216
TI  - Appropriate prescribing of oral beta-lactam antibiotics.
AB  - Beta-lactam antibiotics include penicillins, cephalosporins and related
      compounds. As a group, these drugs are active against many gram-positive, gram
      negative and anaerobic organisms. Information based on "expert opinion" and
      antimicrobial susceptibility testing supports certain antibiotic choices for the
      treatment of common infections, but less evidence-based literature is available
      to guide treatment decisions. Evidence in the literature supports the selection
      of amoxicillin as first-line antibiotic therapy for acute otitis media.
      Alternative drugs, such as amoxicillin-clavulanate, trimethoprim-sulfamethoxazole
      and cefuroxime axetil, can be used to treat resistant infections. Penicillin V
      remains the drug of choice for the treatment of pharyngitis caused by group A
      streptococci. Inexpensive narrow-spectrum drugs such as amoxicillin or
      trimethoprim-sulfamethoxazole are first-line therapy for sinusitis. Animal and
      human bites can be treated most effectively with amoxicillin-clavulanate. For
      most outpatient procedures, amoxicillin is the preferred agent for bacterial
      endocarditis prophylaxis. Beta-lactam antibiotics are usually not the first
      choice for empiric outpatient treatment of community-acquired pneumonia. Based on
      the literature, the role of beta-lactam antibiotics in the treatment of
      bronchitis, skin infections and urinary tract infections remains unclear.

PMID- 10950215
TI  - Breast cancer diagnosis and screening.
AB  - Approximately 180,000 new cases of breast cancer are diagnosed annually,
      accounting for about 48,000 deaths per year in the United States. The screening
      guidelines for the diagnosis of breast cancer are continually changing. Because
      of increased awareness of the signs and symptoms of breast cancer and the use of
      screening mammograms, breast cancers are increasingly being diagnosed at earlier
      stages. Annual mammograms and clinical breast examinations are recommended for
      women older than 40 years. Women older than 20 years should be encouraged to do
      monthly breast self-examinations, and women between 20 and 39 years of age should
      have a clinical breast examination every three years. These guidelines are
      modified for women with risk factors, particularly those with a strong family
      history of breast cancer. Ultrasonographic studies are most useful to evaluate
      cystic breast masses. For solid masses, diagnostic biopsy techniques include fine
      needle aspiration, core biopsy and excisional biopsy.

PMID- 10950217
TI  - Photo quiz. Evaluation of an umbilical lesion.

PMID- 10950219
TI  - HHS updates and guidelines for antiretroviral therapy in HIV infection. Health
      and Human Services.

PMID- 10950218
TI  - Protecting consumers by safeguarding animal health.

PMID- 10950220
TI  - Screening for iron deficiency anemia among children and adolescents.

PMID- 10950221
TI  - Donor responsibilities in rolling back malaria.

PMID- 10950222
TI  - Sodium-hydrogen exchange in myocardial reperfusion injury.

PMID- 10950223
TI  - Treatment of head lice.

PMID- 10950224
TI  - Are atherosclerotic processes involved in aortic-valve calcification?

PMID- 10950225
TI  - Oral tolerance and autoimmune diabetes--will hope triumph over experience?

PMID- 10950226
TI  - Assessment of therapeutic index of inhaled steroids.

PMID- 10950227
TI  - Cautious approach to use of non-heart-beating donors.

PMID- 10950228
TI  - Tri-iodothyronine treatment in children after cardiac surgery: a double-blind,
      randomised, placebo-controlled study.
AB  - BACKGROUND: Serum thyroid hormone concentrations decline transiently during
      critical illness and after surgical procedures. We investigated prospectively the
      endocrine and haemodynamic effects of tri-iodothyronine treatment after
      cardiopulmonary bypass operations in children with congenital cardiac
      malformations. METHODS: We did a randomised, double-blind, placebo-controlled
      trial, in which 40 children (median age 0.6 years; range 2 days to 10.4 years)
      were randomly assigned placebo (saline) or one daily infusion of tri
      iodothyronine (2 microg/kg bodyweight on day 1 after surgery and 1 microg/kg
      bodyweight on subsequent postoperative days up to 12 days after surgery. Before
      and 2 h, 24 h, and 72 h after the first infusion, plasma concentrations of
      thyroid hormones were measured by RIA, and systolic cardiac function was
      evaluated by echocardiography. During the postoperative course intensive-care
      measures were assessed by use of the therapeutic intervention scoring system.
      FINDINGS: In all patients, postoperative plasma concentrations of thyrotropin,
      thyroxine, free thyroxine, tri-iodothyronine were abnormally low and plasma
      concentrations of reverse tri-iodothyronine were raised. After start of
      treatment, tri-iodothyronine was significantly higher in patients given tri
      iodothyronine than in those receiving placebo, whereas thyrotropin, thyroxine,
      free thyroxine, and reverse tri-iodothyronine remained similar in the two groups.
      At discharge, thyroid hormones of all patients were within the normal range, but
      thyrotropin secretion increased to plasma concentrations higher than those seen
      before treatment. The mean change of cardiac index was significantly higher in
      children given tri-iodothyronine (20.4% [SD 19.6] vs 10.0% [15.2]; p=0.004).
      Systolic cardiac function improved most in patients given tri-iodothyronine after
      longer cardiopulmonary bypass operations. Overall, patients given tri
      iodothyronine had significantly lower mean treatment scores. INTERPRETATION:
      Treatment of children with tri-iodothyronine after cardiopulmonary bypass
      operations raises tri-iodothyronine plasma concentrations and improves myocardial
      function especially in patients with low postoperative cardiac output without
      adverse events, and without delaying postoperative recovery of thyroid function.
      Furthermore, tri-iodothyronine reduces the need for postoperative intensive care.

PMID- 10950229
TI  - Hysterectomy and urinary incontinence: a systematic review.
AB  - BACKGROUND: Serious complications after hysterectomy are estimated to occur in
      around six women per 10,000 hysterectomies in the USA. We did a systematic review
      of evidence that hysterectomy is associated with urinary incontinence. METHODS:
      We identified English-language and non-English-language articles registered on
      MEDLINE from January, 1966, to December, 1997, did manual review of references,
      and consulted specialists. We identified 45 articles reporting on the association
      of urinary incontinence and hysterectomy. We selected reports that presented
      original data on development of incontinence in women who underwent hysterectomy
      compared with those who did not. Results were abstracted by two independent
      reviewers and summarised with a random-effects model. FINDINGS: 12 papers met our
      selection criteria--eight cross-sectional studies, two prospective cohort
      studies, one case-control study, and one randomised controlled trial. The summary
      estimate was consistent with increased odds for incontinence in women with
      hysterectomy. Because incontinence might not develop for many years after
      hysterectomy, we stratified the findings by age at assessment of incontinence.
      Among women who were 60 years or older, the summary odds ratio for urinary
      incontinence was increased by 60% (1.6 [95% CI 1.4-1.8]) but odds were not
      increased for women younger than 60 years. INTERPRETATION: When women are
      counselled about sequelae of hysterectomy, practitioners should discuss the
      possibility of an increased likelihood of incontinence in later life.

PMID- 10950230
TI  - Comparison of wet combing with malathion for treatment of head lice in the UK: a
      pragmatic randomised controlled trial.
AB  - BACKGROUND: Concern about the effectiveness and toxicity of insecticide lotions
      has led to promotion of mechanical methods to remove head lice. We compared the
      effectiveness of "bug-busting" (wet combing with a fine-toothed comb) and
      malathion lotion. METHODS: We screened 4037 schoolchildren in two counties in
      Wales, UK (intermediate resistance to malathion). Of 167 found to have head lice,
      81 (aged 3-14 years) were eligible to participate in a randomised controlled
      trial that compared mechanical removal of lice by a commercial kit every 3-4 days
      for 2 weeks with two applications of 0.5% malathion lotion 7 days apart; parents
      carried out both treatments. The outcome measure was the presence of live lice 7
      days after the end of treatment. Analyses were by intention to treat. FINDINGS:
      74 children completed the study and 72 were included in the analysis. The cure
      rate was 38% (12 of 32) for bug-busting and 78% (31 of 40) for malathion.
      Children assigned bug-busting were 2.8 (95% CI 1.5-5.2) times more likely than
      those assigned malathion to have lice at the end of treatment (p=0.0006).
      INTERPRETATION: Malathion lotion was twice as effective as bug-busting, even in
      an area with intermediate resistance. Policies advocating bug-busting as first
      line treatment for head lice in the general population are inappropriate.
      Assessment of the outcome of treatment 1-2 weeks after completion is essential
      for successful management. Only about 50% of participants complied fully with
      treatment, so future trials should be pragmatic in design, avoid false
      incentives, and study representative samples of children.

PMID- 10950231
TI  - Oral insulin administration and residual beta-cell function in recent-onset type
      1 diabetes: a multicentre randomised controlled trial. Diabete Insuline Orale
      group.
AB  - BACKGROUND: Oral administration of autoantigens can slow the progression of beta
      cell destruction in non-obese diabetic mice. We investigated whether oral
      administration of recombinant human insulin could protect residual beta-cell
      function in recent-onset type 1 diabetes. METHODS: We enrolled 131 autoantibody
      positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no
      ketoacidosis at diagnosis, weight loss <10%, polyuria for <6 weeks). They were
      randomly assigned 2.5 mg or 7.5 mg oral insulin daily or placebo for 1 year, in
      addition to subcutaneous insulin therapy. Serum C-peptide concentrations were
      measured in the fasting state and after stimulation, to assess beta-cell
      function. Autoantibodies to beta-cell antigens were assayed. Analyses were by
      intention to treat. FINDINGS: Baseline C-peptide and haemoglobin A1c
      concentrations were similar in the three groups. During follow-up, there were no
      differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo
      in subcutaneous insulin requirements, haemoglobin A1c concentrations, or
      measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17
      [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39
      [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49
      [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry
      influenced treatment effects. No differences were seen in the time-course or
      titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2.
      INTERPRETATION: At the doses used in this trial, oral administration of insulin
      initiated at clinical onset of type 1 diabetes did not prevent the deterioration
      of beta-cell function.

PMID- 10950232
TI  - Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a
      randomised trial.
AB  - BACKGROUND: No satisfactory strategy for reducing high child mortality from
      malaria has yet been established in tropical Africa. We compared the effect on
      under-5 mortality of teaching mothers to promptly provide antimalarials to their
      sick children at home, with the present community health worker approach.
      METHODS: Of 37 tabias (cluster of villages) in two districts with hyperendemic to
      holoendemic malaria, tabias reported to have the highest malaria morbidity were
      selected. A census was done which included a maternity history to determine under
      5 mortality. Tabias (population 70,506) were paired according to under-5
      mortality rates. One tabia from each pair was allocated by random number to an
      intervention group and the other was allocated to the control group. In the
      intervention tabias, mother coordinators were trained to teach other local
      mothers to recognise symptoms of malaria in their children and to promptly give
      chloroquine. In both intervention and control tabias, all births and deaths of
      under-5s were recorded monthly. FINDINGS: From January to December 1997, 190 of
      6383 (29.8 per 1000) children under-5 died in the intervention tabias compared
      with 366 of 7294 (50.2 per 1000) in the control tabias. Under-5 mortality was
      reduced by 40% in the intervention localities (95% CI from 29.2-50.6; paired t
      test, p<0.003). For every third child who died, a structured verbal autopsy was
      undertaken to ascribe cause of mortality as consistent with malaria or possible
      malaria, or not consistent with malaria. Of the 190 verbal autopsies, 13 (19%) of
      70 in the intervention tabias were consistent with possible malaria compared with
      68 (57%) of 120 in the control tabias. INTERPRETATION: A major reduction in under
      5 mortality can be achieved in holoendemic malaria areas through training local
      mother coordinators to teach mothers to give under-5 children antimalarial drugs.

PMID- 10950233
TI  - Comparison of pharmacokinetics and systemic effects of inhaled fluticasone
      propionate in patients with asthma and healthy volunteers: a randomised crossover
      study.
AB  - BACKGROUND: Inhaled corticosteroids are currently the cornerstone of asthma
      treatment. Some studies of high-dose fluticasone propionate in patients with no
      or mild asthma have, however, suggested substantial systemic absorption. We
      investigated the pharmacokinetics of fluticasone propionate in patients with
      asthma receiving appropriate doses for severity. METHODS: We did a double-blind,
      randomised, crossover study in 11 patients with asthma and 13 matched healthy
      controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75%
      and stable on high-dose inhaled corticosteroids). Patients received one 1000
      microg intravenous dose or 1000 microg daily for 7 days inhaled (via spacer
      device) fluticasone propionate. In the 12 h after dosing, we monitored plasma
      fluticasone propionate and cortisol concentrations by mass spectrometry and
      competitive immunoassay with use of direct chemiluminescence. Analysis was by
      intention to treat. FINDINGS: After inhalation, geometric mean values were
      significantly lower in the asthma group than in controls for fluticasone
      propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL(-1) h(
      1) [2262-3949], -62% difference [45-72]; p<0.001), maximum concentrations (117
      [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p<0.001), and systemic
      bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70];
      p=0.001). Intravenous-dose clearance, volume of distribution at steady state,
      plasma half-life, and mean residence time, were similar in the two groups. Less
      suppression of plasma cortisol concentrations was seen in the asthma group than
      in controls 4-12 h after inhaled fluticasone propionate. INTERPRETATION: Systemic
      availability of fluticasone propionate is substantially less in patients with
      moderate to severe asthma than in healthy controls. Inhaled corticosteroids that
      are absorbed through the lungs need to be assessed in patients who are receiving
      doses appropriate for disease severity, and not in normal volunteers.

PMID- 10950234
TI  - Abdominal pain and melaena: an unusual cause.

PMID- 10950235
TI  - Refrigerator content and hospital admission in old people.
AB  - We assessed whether the refrigerator contents of elderly people could be related
      to subsequent admission to hospital. 132 patients aged over 65 years had a
      thorough assessment of their refrigerator contents and the numbers and dates of
      admission were recorded. Elderly people with empty refrigerators were more
      frequently admitted (p=0.032) in the month after assessment and three times
      sooner than those who did not have empty refrigerators (34 vs 100 days, p=0.002).

PMID- 10950236
TI  - Airway remodelling in cough-variant asthma.
AB  - Subepithelial-layer thickening, a pathological feature of airway remodelling, is
      present in cough-variant asthma. In bronchial biopsy samples we found mean
      subepithelial-layer thickness was 7.1 (SE 0.4) microm in patients with cough
      variant asthma, 8.6 (0.4) microm in patients with classic asthma with wheezing,
      and 5.0 (0.2) microm in healthy controls. Thickness was significantly higher in
      patients with asthma than in controls, and was significantly greater in those
      with classic asthma than in those with cough-variant asthma. Early anti
      inflammatory treatment might, therefore, be beneficial in cough-variant asthma,
      as recommended in classic asthma.

PMID- 10950237
TI  - Autoantibody screening in subacute cerebellar ataxia.
AB  - In a retrospective study of 280 sera from patients presenting with cerebellar
      signs, seven of whom had proved positive for the typical paraneoplastic serum
      antibodies that were requested by the clinicians, raised concentrations of
      antibodies to voltage-gated calcium channels or to glutamic acid decarboxylase
      were detected in a further seven sera. Systematic screening for these and other
      antibodies in future cases should help in the diagnosis and management of the
      patients.

PMID- 10950238
TI  - Effect of thalidomide on gastrointestinal toxic effects of irinotecan.
AB  - Irinotecan is the only accepted second-line treatment for colorectal cancer in
      the USA. Doses are, however, frequently limited by associated late-onset
      diarrhoea. Thalidomide has antiangiogenic and immunomodulatory properties and is
      being investigated as an antineoplastic. We did a pilot study of combination
      therapy with thalidomide and irinotecan for metastatic colorectal cancer. In an
      interim analysis of nine patients, thalidomide had almost eliminated the dose
      limiting gastrointestinal toxic effects of irinotecan, especially diarrhoea and
      nausea (each p<0.0001), and eight of nine patients were able to complete the
      chemotherapy course.

PMID- 10950239
TI  - Breast-cancer diagnosis with nipple fluid bFGF.
AB  - Early diagnosis of breast cancer is the key to extending survival of breast
      cancer patients. We found that the concentrations of nipple fluid bFGF (basic
      fibroblast growth factor) was significantly increased in breast-cancer patients
      compared with concentrations in controls (1717 ng/L [SD 706] vs 19 ng/L [19];
      Student's t test p=0.027). Measurement of bFGF in nipple fluid could be a useful
      diagnostic tool for breast cancer, and deserves further study.

PMID- 10950240
TI  - Urinary incontinence: an unrecognised adverse effect with donepezil.
AB  - Donepezil has been licensed for use in Japan to improve cognitive function since
      1999. Among 94 patients with probable Alzheimer's disease who we treated with
      donepezil, seven patients developed urinary incontinence, although this event was
      transient in most patients.

PMID- 10950241
TI  - Curb costs of egg donation, urge US specialists.

PMID- 10950242
TI  - New predictions for total vCJD mortality lower than before.

PMID- 10950243
TI  - Myocardial infarction: changing view of a killer.

PMID- 10950244
TI  - Contaminated milk scare leaves sour taste among consumers.

PMID- 10950245
TI  - Pakistan predicts a polio-free future.

PMID- 10950246
TI  - Delhi hospital lambasted for use of contaminated surgical equipment.

PMID- 10950247
TI  - Global health status: two steps forward, one step back.
AB  - Impressive improvements have occurred in global health status in the past
      century. Unfortunately, these improvements have not been shared equally and
      health in equalities within and among countries are entrenched. The fragility of
      health gains has been seen in response to economic, political, and social changes
      changes, and civil disruption. The limitations of health-status measure hinder
      our ability to map health trends except in the simplest way. There is an urgent
      need for better regional and national health surveillance systems to underpin
      efforts to address the complex mixture of old and new health concerns.

PMID- 10950248
TI  - Inborn errors of metabolism around time of birth.
AB  - Inborn errors of metabolism commonly present around the time of birth. Although
      most affected babies are born healthy and subsequently deteriorate, some
      disorders may present at (or shortly after) birth and a few may be detected by
      antenatal ultrosonography. In many cases, it is important that the diagnosis is
      made quickly and a strategy to identify those at high risk is proposed. Treatment
      should not be delayed for a definitive diagnosis.

PMID- 10950249
TI  - Prevention, not panic--epidemics and trade sanctions.

PMID- 10950250
TI  - Trends in breast cancer incidence, survival, and mortality.

PMID- 10950251
TI  - Trends in breast cancer incidence, survival, and mortality.

PMID- 10950252
TI  - Trends in breast cancer incidence, survival, and mortality.

PMID- 10950253
TI  - Trends in breast cancer incidence, survival, and mortality.

PMID- 10950255
TI  - Heparin in acute coronary syndromes.

PMID- 10950254
TI  - Trends in breast cancer incidence, survival, and mortality.

PMID- 10950256
TI  - Advantages of depot antipsychotics.

PMID- 10950257
TI  - Safe feeding after stroke.

PMID- 10950258
TI  - Safe feeding after stroke.

PMID- 10950259
TI  - High-dose chemotherapy for breast cancer.

PMID- 10950260
TI  - Acquired anaemias and polycythaemia.

PMID- 10950261
TI  - Acquired anaemias and polycythaemia.

PMID- 10950262
TI  - Sweat gland dysfunction in exertional heat illness.

PMID- 10950263
TI  - Neuroprotection disappointment yet aGAIN.

PMID- 10950264
TI  - Sleep attacks in Parkinson's disease.

PMID- 10950265
TI  - Japanese physicians and public respect.

PMID- 10950266
TI  - In defence of genetic association studies.

PMID- 10950267
TI  - Late survivors of Sumatran earthquake.

PMID- 10950268
TI  - What is a smack?

PMID- 10950269
TI  - Primary prevention of HIV-1.

PMID- 10950270
TI  - Mobile-phase-viscosity dependence on DNA separation in slalom chromatography.
AB  - Slalom chromatography (SC) is an alternative chromatographic procedure for the
      separation of relatively large double-stranded DNA molecules and is based on a
      new principle. The retardation of the DNA fragments from the cleavage of the
      Lambda DNA by the KpnI restriction enzyme was studied using an acetonitrile
      phosphate buffer as a mobile phase with various concentrations of viscosity
      modifier (i.e. glycerol) and a C1 column as a stationary phase. The DNA molecule
      retention was accurately described over the glycerol concentration range using a
      model previously established. It was shown that the eluent viscosity increase
      enhanced the slalom chromatographic capacity to separate the DNA fragments. A
      connection between SC and 'hydrodynamic chromatography' processes was predicted
      to link the two processes in a global separation mechanism based on a non
      equilibrium principle.

PMID- 10950271
TI  - On-column refractive index detector for flash chromatography.
AB  - A universal detector for on-column analysis in flash chromatography is reported.
      The detection scheme takes advantage of refractive index changes as analytes move
      through an illuminated region of the column. The column packing material is a
      diffuse scattering medium when the refractive index of the solvent is
      significantly different than that of the packing material. The magnitude of the
      'signal' depends on the degree to which the refractive index mismatch is changed.
      An empirical model that qualitatively accounts for the observed trends is
      presented. This detection scheme provides a simple, inexpensive means to monitor
      the end of a flash chromatography column in order to determine the exit time of
      the species of interest, thus greatly reducing the post-column analysis time.
      Additionally, the detector is movable along the length of the column, offering
      the potential to monitor separations as they occur.

PMID- 10950272
TI  - High-performance liquid chromatography coupled to enzyme-amplified biochemical
      detection for the analysis of hemoglobin after pre-column biotinylation.
AB  - The determination of proteins with enzyme-amplified biochemical detection (EA
      BCD) coupled on-line with high-performance liquid chromatography (HPLC) is
      demonstrated. The EA-BCD system was developed to detect biotin-containing
      compounds. Hemoglobin, which was used as a model compound, was biotinylated prior
      to sample introduction. Several biotinylation parameters, such as pH and removal
      of excess biotinylation reagent, were investigated. After biotinylation samples
      were introduced to HPLC followed by EA-BCD. To the HPLC effluent, alkaline
      phosphatase label streptavidin (S-AP) was added, which possesses high affinity to
      biotin and biotin-containing compounds. Excess S-AP was removed by means of an
      immobilized biotin column followed by substrate addition. The non-fluorescent
      substrate is converted to a highly fluorescent product by the enzyme label. A
      detection limit of 2 femtomol biotinylated Hb was achieved with good
      reproducibility and linearity. However, biotinylation at low analyte
      concentration suffers from low yield due to slow reaction kinetics. Finally, Hb
      was successfully extracted from urine with a recovery of 94%.

PMID- 10950273
TI  - Interpretive optimisation strategy applied to the isocratic separation of phenols
      by reversed-phase liquid chromatography with acetonitrile-water and methanol
      water mobile phases.
AB  - An optimisation protocol is presented for the resolution of complex mixtures in
      isocratic RPLC with binary mobile phases of organic solvent and water, which is
      based on the prediction of peak position and shape of the individual compounds. A
      good description of the retention was achieved through the application of
      statistical weights to the widely used linear or quadratic relationships between
      the logarithm of the retention factor (log k) and the organic solvent
      concentration in the mobile phase. The maximisation of the product of peak
      purities for each compound is shown as a competitive resolution strategy versus
      the worst value of a selectivity parameter. Peak purities allow one to associate
      a single resolution value to each compound, which is not affected by the identity
      of the interfering peaks. It is shown how when full resolution is not achieved
      with a single mobile phase, the same experimental data set (retention factors,
      asymmetries and efficiencies) can be used for finding two or three optimal
      complementary mobile phases (CMPs). Each CMP resolves fully some compounds in the
      mixture, while the remaining compounds can overlap among them. The elementary
      limiting resolutions, which measure the maximal separation degree for each
      compound, are also given as a useful guide in the selection of the elution
      conditions. A mixture of 13 phenols (phenol, chloro-, bromo-, nitro- and methyl
      derivatives), eluted with acetonitrile-water or methanol-water mobile phases, is
      used to show the proposed methodology.

PMID- 10950274
TI  - Experimental support differenciating two proposed chiral recognition models for
      the resolution of N-(3,5-dinitrobenzoyl)-alpha-arylalkylamines on high
      performance liquid chromatography chiral stationary phases.
AB  - In rationalizing the odd chromatographic behavior for the separation of the
      enantiomers of N-(3,5-dinitrobenzoyl)-alpha-arylalkylamines on HPLC chiral
      stationary phases (CSPs) derived from alpha-(6,7-dimethyl-1-naphthyl)alkylamines,
      we initially suggested the occurrence of two competing, opposite sense chiral
      recognition processes termed the "dipole-stacking process" and the "hydrogen
      bonding process". A simplified "single mechanism" model was later suggested with
      the importance of face to edge pi-pi interaction between aromatic rings come to
      recognized. The initial and subsequent chiral recognition models can be
      differentiated by noting the chromatographic trends for the enantioseparation of
      a homologous series of N-(3,5-dinitrobenzoyl)-alpha-(p-alkylphenyl)ethylamines on
      the aforementioned CSPs. Data so obtained were consistent with the second "single
      mechanism" model but not with the first "two competing mechanism" model. From
      these results, it has been concluded that the "single mechanism" model is more
      plausible than the "two competing mechanism" model.

PMID- 10950275
TI  - Quantitative determination of isoflavones and coumestrol in soybean by column
      liquid chromatography.
AB  - Four different stationary phases and a variety of solvents in varying proportions
      were examined in this study. Daidzein, genistein, formononetin, biochanin A and
      coumestrol were separated within 24 min on a phenyl column with acetonitrile
      water (33:67, v/v) as eluent. The proposed method showed an acceptable
      repeatability with a RSD of quantitation <6%. The mean recoveries of daidzein,
      genistein, formononetin, biochanin A and coumestrol from soybean ranged from 89
      to 104%. The identity of the individual analytes was confirmed by LC-MS-MS. The
      four isoflavones and coumestrol were isolated from soybean by hydrolysis with
      acid and heat. Neutralization of the soybean samples prior to identification did
      not alter the concentration of daidzein and genistein in soybean.

PMID- 10950276
TI  - High-speed counter-current chromatography of apple procyanidins.
AB  - Apple procyanidins were separated by high-speed counter-current chromatography
      using a type-J multilayer coil planet centrifuge. Several two-phase solvent
      systems with a wide range of hydrophobicities from a non-polar hexane system to
      polar n-butanol systems were evaluated their performance in terms of the
      partition coefficient and the retention of the phase. The best separation of
      procyanidins B and C was achieved with a two-phase solvent system composed of n
      butanol-methyl tert.-butyl ether-acetonitrile-0.1% trifluoroacetic acid (2:4:3:8)
      using the lower phase as a mobile at a flow-rate of 1.0 ml/min.

PMID- 10950277
TI  - Separation of coumarins from Archangelica officinalis in high-performance liquid
      chromatography and thin-layer chromatography systems.
AB  - Complex, multicomponent mixtures are difficult to separate in a single
      chromatographic run. Therefore, the possibility to separate twelve coumarins from
      Archangelica officinalis was studied by combining a HPLC and a TLC system. HPLC
      optimized by the use of DryLab for Windows software was performed on RP-18 column
      and TLC was performed on silica plates. Fractions from the RP column were
      evaporated, applied on silica plate and developed in non-aqueous solvent.
      Possibilities of complete separation of investigated coumarins were discussed in
      RP and NP systems. The result of their complete separation was presented by HPLC
      chromatograms, DryLab simulated chromatograms and a video scan of TLC plate.

PMID- 10950278
TI  - Poly(allylamine) beads as selective sorbent for preconcentration of formaldehyde
      and acetaldehyde in high-performance liquid chromatographic analysis.
AB  - Formaldehyde and acetaldehyde in water were determined by preconcentration with
      poly(allylamine) beads, derivatization with 2,4-dinitrophenylhydrazine (DPH) and
      analysis by HPLC. Poly(allylamine) beads (0.5 g) were used to adsorb formaldehyde
      and acetaldehyde at 1.2-150 microg l(-1) and 3.5-220 microg l(-1) from water (1
      l). The concentration factor is 50 fold. The aldehydes were eluted and
      derivatized with 2 mM DPH in 0.5 M H2SO4 (10 ml). The time of analysis was 1 h.
      The detection limits (S/N=3) for formaldehyde and acetaldehyde were 0.6 and 2
      microg l(-1), respectively.

PMID- 10950279
TI  - Rapid and sensitive analysis of azadirachtin and related triterpenoids from Neem
      (Azadirachta indica) by high-performance liquid chromatography-atmospheric
      pressure chemical ionization mass spectrometry.
AB  - Based on reversed-phase high-performance liquid chromatography (RP-HPLC) and
      atmospheric pressure chemical ionization (APCI) mass spectrometry, a HPLC-MS
      method was developed to permit the rapid qualitative and quantitative analysis of
      azadirachtin and related tetranortriterpenoids from seeds and tissue cultures of
      Neem (Azadirachta indica). APCI+ standard scanning mass spectra of the major Neem
      triterpenoids were recorded and utilized to select suitable ions for selected ion
      monitoring (SIM). Transitions for selective reaction monitoring (SRM) were based
      on MS-MS experiments. Using SIM, major Neem triterpenoids were detected in callus
      culture material and seed kernels of A. indica. The limit of detection for
      azadirachtin in extract samples (approximately 1 ng ml(-1) or 10 pg in SIM mode)
      was determined to be (with respect to injected absolute amounts) approximately
      1000-times lower than values quoted in the literature for existing HPLC methods
      (approximately 200 ng ml(-1) or 10 ng). In addition to high sensitivity, the HPLC
      MS method is able to tolerate minimal sample preparation and purification,
      dramatically reducing total analysis time.

PMID- 10950280
TI  - Protein identification platform utilizing micro dispensing technology interfaced
      to matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - An integrated protein microcharacterization/identification platform has been
      developed. The system has been designed to allow a high flexibility in order to
      tackle challenging analytical problems. The platform comprises a cooled
      microautosampler, an integrated system for microcolumn HPLC, and a capillary
      reversed-phase column that is interfaced to matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF-MS) system via a low
      internal volume flow-through microdispenser. The chromatographic separation is
      continuously transferred onto a MALDI target plate as discrete spots as the
      dispenser ejects bursts of droplets of the column effluent in a precise array
      pattern. A refrigerated microfraction collector was coupled to the outlet of the
      flow-through microdispenser enabling enrichment and re-analysis of interesting
      fractions. The use of target plates pre-coated with matrix simplified and
      increased the robustness of the system. By including a separation step prior to
      the MALDI-TOF-MS analysis and hereby minimizing suppression effects allowed us to
      obtain higher sequence coverage of proteins compared to conventional MALDI sample
      preparation methodology. Additionally, synthetic peptides corresponding to
      autophosphorylated forms of the tryptic fragment 485-496 (ALGADDSYYTAR) of
      tyrosine kinase ZAP-70 were identified at sensitivities reaching 150 amol.

PMID- 10950281
TI  - Resolution and identification of the protein components of the photosystem II
      antenna system of higher plants by reversed-phase liquid chromatography with
      electrospray-mass spectrometric detection.
AB  - Reversed-phase liquid chromatography (RPLC) was interfaced to mass spectrometry
      (MS) with an electrospray ion (ESI) source for the separation and accurate
      molecular mass determination of the individual intrinsic membrane proteins that
      comprise the photosystem II (PS II) major light-harvesting complex (LHC II) and
      minor (CP24, CP26 and CP29) antenna system, whose molecular masses range between
      22,000 and 29,000. PS II is a supramolecular complex intrinsic of the thylacoid
      membrane, which plays the important role in photosynthesis of capturing solar
      energy, and transferring it to photochemical reaction centers where energy
      conversion occurs. The protein components of the PS II major and minor antenna
      systems were extracted from spinach thylacoid membranes and separated using a
      butyl-silica column eluted by an acetonitrile gradient in 0.05% (v/v) aqueous
      trifluoroacetic acid. On-line electrospray MS allowed accurate molecular mass
      determination and identification of the protein components of PS II major and
      minor antenna system. The proposed RPLC-ESI-MS method holds several advantages
      over sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the conventional
      technique for studying membrane proteins, including a better protein separation,
      mass accuracy, speed and efficiency.

PMID- 10950282
TI  - Liquid chromatographic profiles of individual compounds of technical toxaphene.
AB  - The elution orders of 20 hexa- to nonachlorobornanes and five hexa- to
      octachlorocamphenes were studied with normal-phase silica and amino phase HPLC,
      reversed-phase HPLC, as well as gel-permeation chromatography (GPC). Twenty-one
      compounds of technical toxaphene (CTTs) are commercially available and four were
      isolated from environmental samples. Structure-activity relationships and
      chromatographic properties were deduced from the data sets derived on these LC
      systems. The retention on silica (low-resolution LC and HPLC) increased with the
      polarity of the CTTs. The elution order of CTTs on amino normal-phase HPLC was,
      for the most part, the same as on silica normal-phase HPLC. The degree of
      chlorination determined the elution order of CTTs on C18 RP-HPLC. CTTs eluted
      from medium-pressure GPC with decreasing molecular size. Chlorobornanes with
      dichloro substituents on the six-membered ring eluted after the chloroboranes
      without geminal chlorine atoms on secondary carbons, indicating that these
      congeners are larger. Altogether, the results increase the knowledge of complex
      substance class and may serve as a tool in order to gain further standard
      components.

PMID- 10950283
TI  - Effect of surface heterogeneity on adsorption on solid surfaces. Application of
      inverse gas chromatography in the studies of energetic heterogeneity of
      adsorbents.
AB  - The paper presents a literature review of the chromatographic methods used for
      investigations of the heterogeneity of solid surfaces. Special attention is paid
      to inverse gas chromatography (IGC). Quantitative characteristics of
      heterogeneity of real solid surfaces including extreme models on adsorption
      centre topography of the "patch-wise" and "random" types are described.
      Analytical and numerical methods used for calculating the adsorption energy
      distribution function as a quantitative measure of surface heterogeneity are
      presented. Special attention is paid to the condensation approximation as well as
      to other approximations based on this assumption. IGC is presented as a quick,
      precise and effective method to characterise physicochemical properties of
      different kinds of adsorbents. Advantages of IGC over traditional methods of gas
      and vapour adsorption are shown.

PMID- 10950284
TI  - Validation of an analytical procedure for polychlorinated biphenyls, coplanar
      polychlorinated biphenyls and polycyclic aromatic hydrocarbons in environmental
      samples.
AB  - This work describes an efficient analytical procedure for the analysis of PCBs
      (polychlorinated biphenyls), coplanar PCBs and PAHs (polycyclic aromatic
      hydrocarbons) from the same sample. The method includes a solvent extraction
      followed by a combined purification-separation step on an alumina-silica column.
      Coplanar PCBs are isolated from the first fraction (PCBs) by a further high
      performance liquid chromatography (HPLC) fractionation on a PYE [2-(1
      pyrenyl)ethyldimethylsilylated silica gel] column. PCBs are identified and
      quantified by gas chromatography (GC) with electron-capture detection whereas GC
      with flame ionization detection or mass spectrometry are used for PAH
      determinations. This method allows the measurement of these contaminants in biota
      and sediment at trace levels as low as 1 pg g(-1) for coplanar PCBs with a
      precision better than 20%.

PMID- 10950285
TI  - Solid-phase microextraction with on-fibre derivatisation applied to the analysis
      of volatile carbonyl compounds.
AB  - We have used a fast, sensitive and efficient method for the analysis of volatile
      carbonyl compounds (saturated aliphatic and unsaturated aldehydes) based on solid
      phase microextraction with on-fibre derivatisation. Pentafluorophenylhydrazine
      was absorbed onto a poly(dimethylsiloxane)/divinylbenzene-coated fibre and
      exposed to the vapours of aldehyde-containing matrices. The hydrazones formed on
      the fibre were desorbed into the gas chromatograph injection port and quantified
      by means of electron-capture detection with high sensitivity (10-90 fmol) and
      good reproducibility (RSD<10%). The method was applied to the headspace-sampling
      of volatile carbonyl compounds released during the thermally-induced degradation
      of sunflower oil.

PMID- 10950286
TI  - Combined ion-pair extraction and gas chromatography-mass spectrometry for the
      simultaneous determination of diamines, polyamines and aromatic amines in Port
      wine and grape juice.
AB  - An accurate and very sensitive method which allows for the simultaneous
      determination of the diamines (1,3-diaminopropane, putrescine and cadaverine), of
      the polyamines (spermidine and spermine), and of the aromatic amines (beta
      phenylethylamine and tyramine) found in Port wines and corresponding grape juices
      is presented. Sample clean-up consisted of the extraction of the amines with the
      ion-pairing reagent bis-2-ethylhexylphosphate dissolved in chloroform followed by
      a back-extraction with 0.1 M HCl. The hydrochloric extract obtained was dried and
      the amines were further derivatized with heptafluorobutyric anhydride and
      analyzed by GC-MS in the selected ion-monitoring mode, with a total run time of
      18 min. Under the adopted conditions, the extraction of all the studied compounds
      was almost complete and the obtained extracts were free of potential interferents
      present in the samples, namely sugars, and most of the amino acids and
      polyphenols. Via the use of a set of five selected internal standards
      (amphetamine, [2H8]putrescine, 1,7-diaminoheptane, norspermidine and
      norspermine), the data obtained from the linearity, repeatability and recovery
      experiments were very good for all the compounds assayed. The corresponding
      limits of detection were invariably below 10 microg l(-1). The method was
      successfully applied to measure the content of biogenic amines in twelve young
      and five aged Port wine samples, eleven grape juice samples as well as in ten
      Portuguese red and white table wines. Results are presented and briefly
      discussed.

PMID- 10950287
TI  - Direct Grignard pentylation of organotin-contaminated lard samples followed by
      capillary gas chromatography with flame photometric detection.
AB  - During a recent investigation of the organotin-contaminated lard samples, a
      simple method was developed by direct Grignard pentylation of lard samples and
      capillary gas chromatography with flame photometric detection using quartz
      surface-induced tin emission. Using HP-1 capillary column with temperature
      programming and FPD detector, pentylated tri-, di-, monometyltin, dioctyltin and
      Sn(IV) can be base-line separated and detected within 20 min. The analysis of
      pentylated tin compounds by GC-MS confirmed the existence of methyltins and
      inorganic tin in lard samples, which was agreeable with the results obtained by
      GC-FPD. The content of organotin compounds was calculated by internal standard
      method in which methyltripropyltin (MeSnPr3) acted as internal standard. The
      results showed that these samples were heavily contaminated with mg/g levels of
      dimethyltin, microg/g levels of tri- and monomethyltin. Among them, one sample
      contained mg/g level of dioctyltin and one contained a little of inorganic form
      of Sn(IV). The recoveries of tri-, di- and monomethyltin were 95.7%, 105.5% and
      105.7%, respectively.

PMID- 10950288
TI  - New methods for determination of glyphosate and (aminomethyl)phosphonic acid in
      water and soil.
AB  - New methods were developed to determine glyphosate, N-(phosphonomethyl)glycine,
      and its major metabolite, (aminomethyl)phosphonic acid in groundwater and soil.
      The methods involve ligand-exchange, anion-exchange and derivatisation and final
      identification and quantification by GC-MS. The limits of quantification in this
      experiment were 0.1 microg l(-1) for both compounds in water and 0.006 microg g(
      1) for both compounds in soil. Decomposition in soil and occurrence in
      groundwater of the herbicide glyphosate was studied after its application for
      weed control on a Swedish railway embankment.

PMID- 10950289
TI  - Qualitative and quantitative analysis of a thermoset polymer, poly(benzoxazine),
      by pyrolysis-gas chromatography.
AB  - The chemical composition of a poly(benzoxazine) thermoset polymer (a copolymer of
      bisphenol-A benzoxazine and tert.-butylphenol benzoxazine) has been studied by
      pyrolysis-gas chromatography (Py-GC). Major pyrolysates have been identified and
      the possible degradation pathways have been investigated. A specific pyrolysate
      was identified for quantitative analysis after carefully proving the linear
      relationship between the pyrolysate signal intensity and monomer concentration
      over a wide range of compositions. A method to determine the concentration of the
      monomer that potentially acts as a cross-linking unit has been developed. In this
      study, Py-GC was shown to be an excellent analytical technique for the
      qualitative and quantitative analysis of thermoset polymers.

PMID- 10950290
TI  - Polymer additive analysis by pyrolysis-gas chromatography. II. Flame retardants.
AB  - Flame retardants are widely used in thermoplastic polymers for household and
      transportation applications. Flame retardants as well as most of the other
      additives in the polymer can be qualitatively analyzed by pyrolysis-gas
      chromatography (Py-GC) simultaneously with the polymer composition. The key to
      successful analysis of flame retardants not only requires a thorough knowledge of
      the various types of flame retardants but also necessitates an understanding of
      the parent polymer and its targeted applications. In this study, several flame
      retardants in different polymer matrices have been studied to demonstrate the
      utility of Py-GC for the analysis of flame retardants. The advantages of Py-GC
      for flame retardants analysis have also been discussed.

PMID- 10950291
TI  - Static subcritical water extraction with simultaneous solid-phase extraction for
      determining polycyclic aromatic hydrocarbons on environmental solids.
AB  - A rapid and very simple method for extracting polycyclic aromatic hydrocarbons
      (PAHs) from soils, sediments, and air particulate matter has been developed by
      coupling static subcritical water extraction with styrene-divinylbenzene (SDB-XC)
      extraction discs. Soil, water, and the SDB-XC disc are placed in a sealed
      extraction cell, heated to 250 degrees C for 15 to 60 min, cooled, and the PAHs
      recovered from the disc with acetone/methylene chloride. If the cells are mixed
      during heating, all PAHs with molecular weights from 128 to 276 are
      quantitatively (>90%) extracted and collected on the sorbent disc and are then
      recovered by shaking with acetone/methylene chloride. After water extraction, the
      sorbent discs can be stored in autosampler vials without loss of the PAHs, thus
      providing a convenient method of shipping PAH extracts from field sites to the
      analytical laboratory. The method gives good quantitative agreement with standard
      Soxhlet extraction, and with certified reference materials for PAH concentrations
      on soil, sediment (SRM 1944), and air particulate matter (SRM 1649a).

PMID- 10950292
TI  - Statistical evaluation of linear solvation energy relationship models used to
      characterize chemical selectivity in micellar electrokinetic chromatography.
AB  - Characterization of retention and selectivity differences between surfactants in
      micellar electrokinetic chromatography (MEKC) using linear solvation energy
      relationships (LSERs) has been given a significant amount of attention in the
      last four years. This report evaluates the validity of using the two LSER models
      that have been used to fit retention in MEKC in the literature. The results and
      the fit of the revised model and parameters developed by Abraham and coworkers
      are compared to the original model developed by Kamlet, Taft, and coworkers.
      LSERs can generally only be used as a comparative tool to describe the
      selectivity differences between surfactant systems used in MEKC. With this in
      mind, it was determined that the results of both models essentially provide the
      same information about these differences. However, the revised model and
      parameters have been found to yield a statistically better fit of the MEKC
      retention data as well as providing more chemically sound LSER coefficients.

PMID- 10950293
TI  - Analysis of anionic metallized azo and formazan dyes by capillary electrophoresis
      mass spectrometry.
AB  - Capillary electrophoresis-mass spectrometry was applied to the separation of
      several anionic dyes containing copper(II), chromium(III), or cobalt(III) as part
      of the dye molecule. The dyes were separated using a 110 cm x 50 microm uncoated
      fused-silica capillary and a 5 mM ammonium acetate buffer (pH 9) containing 40%
      acetonitrile. Excellent separation efficiencies (N = 500,000 plates/column) and
      low detection limits of 20-50 pg (selected ion monitoring, S/N = 10) were
      achieved. Mass spectra were acquired at different cone voltages. At low cone
      voltages (low collision energies), sensitivity was maximized and the mass spectra
      contained only signals of the (multiply charged) molecular ions and low levels of
      sodium ion and proton adducts. At higher cone voltages, the 2:1 (ligand:metal)
      chromium and cobalt dyes showed losses of one of the two dye ligands, accompanied
      by a reduction of the metal. The copper dyes showed signals due to loss of SO2
      and SO3-, but no release of metal. Azo cleavage, otherwise typical of azo dyes,
      was not observed with the metallized dyes.

PMID- 10950295
TI  - Relationship between retention, linear velocity and flow for counter-current
      chromatography.
AB  - A recent paper by Du et al. [J. Chromatogr. A, 835 (1999) 231] showed a very good
      correlation between the retention of stationary phase and the square root of
      mobile phase flow (F(1/2)) for 12 different phase systems in counter-current
      chromatography. This paper shows there is a relationship between the above
      retention and the linear velocity of the mobile phase. In this way, Du et al.'s
      results can be related to the kinematics of the mobile phase flow in the tubing.
      This will open the door for further engineering analysis of this fluid dynamic
      phenomenon.

PMID- 10950294
TI  - Identification of reactive dyes in spent dyebaths and wastewater by capillary
      electrophoresis-mass spectrometry.
AB  - Capillary electrophoresis with diode array detection and mass spectrometry
      combined with solid-phase extraction were employed for the identification of
      reactive vinylsulfone and chlorotriazine dyes and their hydrolysis products in
      spent dyebaths and raw and treated wastewater. Recoveries of dyes from treated
      wastewater as their tetrabutylammonium ion-pairs using C18 reversed-phase
      cartridges ranged from 81 to 121%. Detection limits in sewage effluent of the
      different dyes and hydrolysis products ranged from 23 to 42 microg/l. The method
      was successfully applied to the detection of the hydrolysis products of five
      reactive dyes in influents and effluents of a municipal wastewater treatment
      plant receiving dyehouse effluents.

PMID- 10950296
TI  - Selective deuterium exchange during superheated heavy water chromatography
      nuclear magnetic resonance spectroscopy-mass spectrometry of sulfonamides.
AB  - Superheated deuterium oxide has been investigated as an eluent for reversed-phase
      HPLC on a polystyrene-divinylbenzene column with UV, 1H NMR and MS detection
      using a series of sulfonamides as model compounds. In the course of these
      studies, a selective, specific and efficient deuteration of the methyl groups on
      a pyrimidine ring was observed during chromatography of certain of the
      sulfonamides. The potential of this methodology for producing deuterium-labelled
      compounds from substances bearing suitable substituents is considered. The
      utility of HPLC-NMR-MS as a means for studying on-column reactions is discussed.

PMID- 10950297
TI  - Low-capacity cation-exchange chromatography of ultraviolet-absorbing urinary
      basic metabolites using a reversed-phase column coated with hexadecylsulfonate.
AB  - A low-capacity cation-exchange HPLC method for the determination of UV-absorbing
      organic cations such as amino acids, histidine dipeptides, and creatinine was
      developed. A commercially available reversed-phase column was dynamically coated
      with hexadecylsulfonate, and was successfully used for the cation-exchange
      separation with ethylenediammonium eluting ion at pH 2.5. The coated column was
      enough stable for the specific use with a completely aqueous mobile phase at low
      and constant pH; and the day-to-day reproducibility for retention time was 0.9
      1.7% of RSD (relative standard deviation). The linear relation between
      concentrations and detector responses (area) by using a photodiode-array UV
      detection at 210 nm ranged from 0.2 to 1000 microM (sample size 50 microl) for 1
      methylhistidine, 3-methylhistidine, histidine, creatinine, anserine, carnosine,
      and homocarnosine, and from 0.5 to 2000 microM for creatine, tyrosine, and
      phenylalanine, with less than 5% of RSD. The UV spectrum (190-300 nm) obtained
      during chromatography was very indicative for each analyte. Overall recoveries
      were 97-104%. The developed HPLC method in conjunction with preliminary
      fractionation technique could be applied to the analysis of urine of patient with
      metabolic disorder such as phenylketonuria.

PMID- 10950298
TI  - Characterization of a chemical artifact in the liquid chromatographic
      determination of 3-butyn-2-one using the 2,4-dinitrophenylhydrazine method.
AB  - This study reports the identification of a chemical artifact occurring in the
      liquid chromatographic analysis of 3-butyn-2-one by means of the 2,4
      dinitrophenylhydrazine (DNPH) method. Besides the expected derivatization
      reaction to the corresponding butynone DNPhydrazone, a rearrangement was
      observed, thus leading to the formation of 3-methyl-1-(2',4'
      dinitrophenyl)pyrazol (DNPP). Although the rearrangement product and the
      hydrazone can easily be separated by means of liquid chromatography, problems
      arise from coelution of the pyrazol with the formaldehyde DNPhydrazone.
      Identification of the artifact by means of UV-Vis spectroscopy using dual
      wavelength or diode array detection is discussed.

PMID- 10950299
TI  - Separation of gallic acid from Cornus officinalis Sieb. et Zucc by high-speed
      counter-current chromatography.
AB  - Gallic acid was separated from a n-butanol extract of the fruit of Cornus
      officinalis Sieb. et Zucc by high-speed countercurrent chromatography in two
      steps using two solvent systems composed of ethyl-acetate-ethanol n-butanol-water
      (5:1.8:6, v/v/v) and ethyl acetate-ethanol-water (5:0.5:6, v/v/v) successively.
      From 1 g of n-butanol extract the method produced 60 mg of gallic acid at a
      purity of 97%.

PMID- 10950300
TI  - Fullerenes-extracted soot: a new adsorbent for collecting volatile organic
      compounds in ambient air.
AB  - Fullerenes-extracted soot (FES) is the by-product of fullerenes production.
      Retention characteristics at different temperatures for 17 volatile organic
      compounds (VOCs) on FES are measured. The adsorption and desorption efficiencies
      for VOCs on FES adsorbent tubes range from 40.8 to 117%, most of them being 100+/
      20%. The values are compared with Tenax GR, an adsorbent commonly used in
      environmental analysis. FES can be used as an adsorbent of low cost to collect
      VOCs in environmental samples.

PMID- 10950301
TI  - Analysis of flufenacet in soil, wheat grain and straw by gas chromatography.
AB  - An analytical procedure for detecting residues of a new herbicide, flufenacet, in
      soil, wheat grain and straw by gas chromatographic method using various solvents
      and extraction methods was standardized. The best results were obtained when
      samples fortified with flufenacet and were extracted with acetone-0.2 M HCl
      (95:5) using a horizontal shaker for soil and Soxhlet extractor for plant
      samples. The clean up was done by partitioning with dichloromethane. The GC
      equipped with an electron-capture detector and a column packing of HP-1 as
      stationary phase and nitrogen as a carrier gas at a flow-rate of 15 ml min(-1)
      was used. Temperatures of oven, injector and detector were adjusted at 190, 210
      and 270 degrees C, respectively. The retention time of flufenacet was 2.07 min.
      The herbicide recoveries ranged between 81 to 100% from the three matrices.

PMID- 10950302
TI  - A view into the origin of life: aminoacyl-tRNA synthetases.

PMID- 10950304
TI  - Adducin: structure, function and regulation.
AB  - Adducin is a ubiquitously expressed membrane-skeletal protein localized at
      spectrin-actin junctions that binds calmodulin and is an in vivo substrate for
      protein kinase C (PKC) and Rho-associated kinase. Adducin is a tetramer comprised
      of either alpha/beta or alpha/gamma heterodimers. Adducin subunits are related in
      sequence and all contain an N-terminal globular head domain, a neck domain and a
      C-terminal protease-sensitive tail domain. The tail domains of all adducin
      subunits end with a highly conserved 22-residue myristoylated alanine-rich C
      kinase substrate (MARCKS)-related domain that has homology to MARCKS protein.
      Adducin caps the fast-growing ends of actin filaments and also preferentially
      recruits spectrin to the ends of filaments. Both the neck and the MARCKS-related
      domains are required for these activities. The neck domain self-associates to
      form oligomers. The MARCKS-related domain binds calmodulin and contains the major
      phosphorylation site for PKC. Calmodulin, gelsolin and phosphorylation by the
      kinase inhibit in vitro activities of adducin involving actin and spectrin.
      Recent observations suggest a role for adducin in cell motility, and as a target
      for regulation by Rho-dependent and Ca2+-dependent pathways. Prominent
      physiological sites of regulation of adducin include dendritic spines of
      hippocampal neurons, platelets and growth cones of axons.

PMID- 10950303
TI  - The plasma membrane proton-translocating ATPase.
AB  - Living cells require membranes and membrane transporters for the maintenance of
      life. After decades of biochemical scrutiny, the structures and molecular
      mechanisms by which membrane transporters catalyze transmembrane solute movements
      are beginning to be understood. The plasma membrane proton-translocating
      adenosine triphosphatase (ATPase) is an archetype of the P-type ATPase family of
      membrane transporters, which are important in a wide variety of cellular
      processes. The H+-ATPase has been crystallized and its structure determined to a
      resolution of 8 angstrom in the membrane plane. When considered together with the
      large body of biochemical information that has been accumulated for this
      transporter, and for enzymes in general, this new structural information is
      providing tantalizing insights regarding the molecular mechanism of active ion
      transport catalyzed by this enzyme.

PMID- 10950305
TI  - Life without myoglobin.
AB  - Hemoproteins are widely distributed among prokaryotes, unicellular eukaryotes,
      plants and animals [1]. Myoglobin, a cytoplasmic hemoprotein that is restricted
      to cardiomyocytes and oxidative skeletal myofibers in vertebrates, has been
      proposed to facilitate oxygen transport to the mitochondria [1-3]. This
      cytoplasmic hemoprotein was the first protein to be subjected to definitive
      structural analysis and has been a subject of long-standing and ongoing interest
      to biologists [1-3]. Recently, we utilized gene disruption technology to generate
      mice that are viable and fertile despite a complete absence of myoglobin [4].
      This unexpected result led us to reexamine existing paradigms regarding the
      function of myoglobin in striated muscle.

PMID- 10950306
TI  - Structure and function of small heat shock/alpha-crystallin proteins: established
      concepts and emerging ideas.
AB  - Small heat shock/alpha-crystallin proteins are defined by conserved sequence of
      approximately 90 amino acid residues, termed the alpha-crystallin domain, which
      is bounded by variable amino- and carboxy-terminal extensions. These proteins
      form oligomers, most of uncertain quaternary structure, and oligomerization is
      prerequisite to their function as molecular chaperones. Sequence modelling and
      physical analyses show that the secondary structure of small heat shock/alpha
      crystallin proteins is predominately beta-pleated sheet. Crystallography, site
      directed spin-labelling and yeast two-hybrid selection demonstrate regions of
      secondary structure within the alpha-crystallin domain that interact during
      oligomer assembly, a process also dependent on the amino terminus. Oligomers are
      dynamic, exhibiting subunit exchange and organizational plasticity, perhaps
      leading to functional diversity. Exposure of hydrophobic residues by structural
      modification facilitates chaperoning where denaturing proteins in the molten
      globule state associate with oligomers. The flexible carboxy-terminal extension
      contributes to chaperone activity by enhancing the solubility of small heat
      shock/alpha-crystallin proteins. Site-directed mutagenesis has yielded proteins
      where the effect of the change on structure and function depends upon the residue
      modified, the organism under study and the analytical techniques used. Most
      revealing, substitution of a conserved arginine residue within the alpha
      crystallin domain has a major impact on quaternary structure and chaperone action
      probably through realignment of beta-sheets. These mutations are linked to
      inherited diseases. Oligomer size is regulated by a stress-responsive cascade
      including MAPKAP kinase 2/3 and p38. Phosphorylation of small heat shock/alpha
      crystallin proteins has important consequences within stressed cells, especially
      for microfilaments.

PMID- 10950307
TI  - DNA repeat expansions and human disease.
AB  - The repeat expansion diseases are genetic disorders caused by intergenerational
      expansions of a specific tandem DNA repeat. These disorders range from mildly to
      severely debilitating or fatal, and all have limited treatment options. How
      expansion occurs and causes disease is only now beginning to be understood.
      Efforts to model expansion in mice have so far met with only limited success,
      perhaps due to a requirement for specific cis- or trans-acting factors. In vitro
      studies and data from bacteria and yeast suggest that in addition to secondary
      structures formed by the repeats, components of the DNA replication and
      recombination machinery are important determinants of instability. The
      consequences of expansion differ depending on where in the gene the repeat tract
      is located, and range from reduction of transcription initiation to protein
      toxicity. Recent advances are beginning to make rational approaches to the
      development of therapies possible.

PMID- 10950308
TI  - New concepts in regulation and function of the insulin-like growth factors:
      implications for understanding normal growth and neoplasia.
AB  - The insulin-like growth factors (IGFs) are a ubiquitous family of growth factors,
      binding proteins and receptors that are involved in normal growth and
      development. They are also implicated in numerous pathological states, including
      malignancy. IGF-II is a commonly expressed growth factor in many tumors and may
      enhance tumor growth, acting via the overexpressed IGF-I receptor, a cell-surface
      tyrosine kinase receptor. The IGF-I receptor may be overexpressed due to
      mutations in tumor suppression gene products such as p53 and WT-1 or growth
      factors such as bFGF and PDGF. Thus, this family of growth factors, especially
      the IGF-I receptor, may present an excellent target for new therapeutic agents in
      the treatment of cancer and other disorders of excessive cellular proliferation.

PMID- 10950309
TI  - Regulation of BMP/Dpp signaling during embryonic development.
AB  - Bone morphogenetic protein-4 (BMP-4) and its Drosophila ortholog, decapentaplegic
      (Dpp), are multifunctional developmental regulators. Both gain-of-function and
      loss-of-function studies demonstrate that the biological activity and signaling
      range of these morphogens must be strictly regulated to ensure normal embryonic
      patterning. BMP-4 and Dpp are produced from inactive precursors that are
      proteolytically cleaved, following which the active ligand is secreted into the
      extracellular space. Binding of BMP-4 or Dpp to its cognate receptor leads to
      phosphorylation of intracellular signal-transducing Smad proteins that then form
      hetero-oligomers, translocate to the nucleus and modulate transcription of target
      genes. Recent studies have shown that the BMP signal transduction cascade can be
      modulated at every step of this process.

PMID- 10950310
TI  - Regulation of pre-T-cell development.
AB  - One important pillar of cellular immune defense in mammals is the T-lymphoid
      compartment which produces cells that are able to specifically recognize foreign
      peptide antigens through a membrane-bound receptor. These T-cells can trigger a
      variety of defense mechanisms upon antigen stimulation ranging from the
      production of potent cytokines to the direct killing of virus-infected cells. The
      production of such highly specialized T-cells takes place in the thymus and
      requires a stringent process of differentiation and selection of precursor cells
      that are delivered from the bone marrow. In the thymus, several waves of
      proliferative expansion and selection ensure the production of a large repertoire
      of antigen-specific T-cells that each bear a unique T-cell receptor (TCR) which
      is able to recognize foreign antigens but can tolerate the own host-specific
      peptide structures. Education of precursors to mature T-cells in the thymus
      requires a dense network of regulatory processes acting at receptor-ligand
      interactions, signal transduction, genomic rearrangement of TCR gene loci, cell
      cycle progression, transcriptional control and programmed cell death.

PMID- 10950311
TI  - Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein
      after induction of airway inflammation in asthmatics.
AB  - The Clara cell 16 kDa protein (CC16) maps to an atopy-associated region of
      chromosome 11 and has been ascribed an anti-inflammatory function. Using reverse
      phase HPLC and Western blot analysis, we have evaluated the polypeptide pattern
      in bronchoalveolar lavage (BAL) fluid retrieved from asthmatics, before and after
      induction of airway inflammation by low-dose allergen inhalation challenge. A
      prominent decrease of CC16 was seen after induction of inflammation, and a
      further CC16 decrease was observed in lavage fluid where surfactant had been
      removed. Reduced levels of pulmonary CC16 may cause loss of anti-inflammatory
      activity in the airways and contribute to the development of airway inflammation
      in asthma.

PMID- 10950312
TI  - Comment concerning the review article: The Diels-Alder reaction and biopolymer
      catalysis by T.M. Tarasow and B.E. Eaton.

PMID- 10950313
TI  - The humane societies.

PMID- 10950314
TI  - Lay CPR trainees: retraining, confidence and willingness to attempt resuscitation
      4 years after training.
AB  - Two independent samples of 800 lay CPR trainees from an original cohort of 7584
      were surveyed postally 4 years after training. Only 2% of respondents had used
      CPR, but 92 had used other aspects of their life support training. Those who had
      retrained were more confident than those who had not and 89% of those who had not
      retrained were willing to do so. More than 80% expressed willingness to perform
      full CPR on casualties who were unknown to them, but this fell to 40% where
      facial blood was present and 48% where the victim was a gay man.

PMID- 10950315
TI  - Outcomes of out-of-hospital ventricular fibrillation: their association with time
      to defibrillation and related issues in the defibrillation program in Japan.
AB  - The aim of this study was to provide data on the outcomes of out-of-hospital
      cardiac arrest caused by ventricular fibrillation (VFOHCA) and analyze factors
      influencing patient outcomes in order to further improve EMS system performance
      in the resuscitation of VFOHCA patients in Japan. A datasheet was mailed to the
      fire defense headquarters throughout Japan, and returned data were analyzed for
      614 cases of VFOHCA that occurred from January 1 through December 31, 1996. In
      relation to the time interval from receipt of emergency call to defibrillation,
      the subjects were stratified into five groups: 0-8 (n = 39), 9-12 (n = 87), 13-16
      (n = 154), 17-20 (n = 118) and more than 21 min (n = 216). The discharge survival
      rates were 18*, 13.8*, 5.2, 4.2 and 4.2%, respectively (*P < 0.05). When
      defibrillation was delivered within 12 min after a call, 30.2% (38/126) converted
      to pulse-generating rhythm (PGR) after defibrillation and 43.6% (17/39) of
      patients with PGR on arrival at the hospital survived to discharge. In spite of
      these findings, a marked delay to defibrillation (more than 13 min) was observed
      in the majority (79.5%). The data shown in this study demonstrated that important
      issues that limit the benefits of an early defibrillation program reside in the
      EMS system.

PMID- 10950316
TI  - Early fluid resuscitation improves outcomes in severely burned children.
AB  - BACKGROUND: Recent evidence suggests that timely fluid resuscitation can
      significantly reduce multiorgan failure and mortality in thermally injured
      children. In this study, children who received fluid resuscitation within 2 h of
      a thermal injury were compared with children in which fluid resuscitation was
      delayed by 2-12 h. We hypothesized that fluid resuscitation given within 2 h of a
      thermal injury attenuates renal failure, cardiac arrest, cardiac arrest deaths,
      incidence of sepsis, and overall mortality. METHODS: A retrospective chart review
      was made on 133 children admitted to our institute from 1982 to 1999 with scald
      or flame burns covering more than 50% of their body surface area. Comparisons
      between early (< 2 h of injury) or delayed (> or = 2 h of injury) fluid
      resuscitation were made in children experiencing renal failure, sepsis, non
      survivors with cardiac arrest requiring pulmonary and advanced life support, and
      overall mortality. Comparisons were made using the chi2-test with Yates'
      continuity correction and joint binomial confidence intervals using the
      Bonferroni correction. RESULTS: The incidence of sepsis, renal failure, non
      survivors with cardiac arrest, and overall mortality was significantly higher in
      burned children receiving fluid resuscitation that was delayed by 2 h or more
      compared with those receiving fluid resuscitation within 2 h of thermal injury (P
      < 0.001). CONCLUSIONS: Data suggest that fluid resuscitation, given within 2 h of
      a thermal injury, may be one of the most important steps in the prevention of
      multi-organ failure and mortality.

PMID- 10950317
TI  - Using the ability to perform CPR as a standard of fitness: a consideration of the
      influence of aging on the physiological responses of a select group of first
      aiders performing cardiopulmonary resuscitation.
AB  - OBJECTIVE: Previous research has suggested that the physical demands of
      performing cardiopulmonary resuscitation (CPR) are relatively low. However, the
      subjects studied have generally been of a young age. The aim of this study was to
      test the hypothesis, in null form, that the physiological responses to the
      performance of single operator CPR for 10 min are independent of age.
      Confirmation of the hypothesis would allow the use of a period of time performing
      CPR as a socially non-discriminatory means of testing ability across a wide
      spectrum of age. DESIGN: 33 St. John Operations Branch members (a sample of
      convenience), aged between 18 and 65 years, were examined whilst performing 10
      min of single operator CPR on a manikin at St. John Ambulance Headquarters,
      Adelaide, South Australia. Heart rate and cardiac rhythm were monitored
      continuously. Blood pressure was recorded at baseline and the end of the 3rd, 6th
      and 9th min of CPR. Subjects also rated their perceived level of activity using
      the 15-point Borg rating scale every 3 min and at the end of the test. RESULTS:
      The calculated rate-pressure product did not vary significantly with age, either
      at rest or in response to performing CPR. The rate-pressure product increased
      significantly (P < 0.05) whilst performing CPR. There was no effect of age on the
      perceived level of exertion, which also increased significantly during CPR as
      compared with rest. CONCLUSION: There was no significant effect of age on the
      physiological responses to the performance of 10 min of single operator CPR in
      this select group.

PMID- 10950318
TI  - Increased plasma free cyclic-AMP levels following major trauma and their
      relevance to the immune response.
AB  - BACKGROUND: Following injury, neutrophil mobilisation is an important element of
      the immune response. The ideal features of an agent responsible for this
      mobilisation would include the ability to mobilise neutrophils without activating
      them, and rapid reversibility. This study investigates the hypothesis that raised
      levels of plasma adrenaline following trauma act via cyclic adenosine
      monophosphate (cAMP) to mobilise neutrophils, and measures the amount of cAMP
      extruded from cells into the plasma following injury. METHODS: 20-ml samples of
      venous blood were drawn from 34 trauma patients within 3 h of injury and divided
      between three sample tubes: (1) ethylene diamine tetra-acetic acid anticoagulant
      (EDTA) for full blood count; (2) cooled EDTA for cAMP levels; and (3) cooled
      lithium heparin for catecholamines. The latter two tubes were immediately
      centrifuged at low temperature and the supernatant plasma deep frozen pending
      analysis. Adrenaline was measured using high pressure liquid chromatography
      (HPLC) and cAMP measured by an enzyme immunoassay technique. RESULTS: 34
      patients, six of whom had sustained minor trauma (ISS 1-8), 12 moderate trauma
      (ISS 9-15) and 16, major trauma (ISS 16 and above) were studied. Median age was
      39 years (range 16-77) and 30 patients were male. Plasma adrenaline levels were
      available for 28 of the patients. Plasma free cAMP levels were significantly
      raised in patients with major trauma (P < 0.006). There were positive
      correlations between the plasma levels of cAMP and adrenaline (rho 0.660, P =
      0.011), adrenaline and neutrophil count (rho 0.654, P = 0.01) and cAMP and
      neutrophil count (rho 0.508, P = 0.013). CONCLUSIONS: Evidence is presented of
      the possible inter-relationships between neutrophil counts, adrenaline levels and
      cAMP levels following injury, supporting the proposition that neutrophil
      mobilisation pathways are activated early via beta-adrenergic stimulation.

PMID- 10950319
TI  - Jugular vein temperature reflects brain temperature during hypothermia.
AB  - PURPOSE: The neuroprotective properties of mild to moderate hypothermia are well
      recognized but may not be employed correctly because brain temperature cannot
      usually be measured directly. This study investigated the jugular vein as a more
      accessible site that accurately reflects the actual brain temperature during
      mild, induced hypothermia. METHODS: We selected ten mongrel dogs (mean weight 12
      +/- 2 kg) and measured temperatures of the brain, jugular vein, cisterna magna,
      pulmonary artery and rectum during hypothermia, including cooling and rewarming.
      The brain temperature needle probe was inserted 2.0 cm into the parenchyma. A
      temperature probe was placed in the cisterna magna with an epidural needle. Swan
      Ganz thermistor probes measured the jugular venous and pulmonary artery blood
      temperatures. RESULT: The brain temperature decreased from 37.5 +/- 0.3 to 33.0
      +/- 0.3 degrees C over an average 150 +/- 45 min cooling period. Stable cool was
      maintained for 245 +/- 32 min, followed by 165 +/- 50 min for rewarming from 33.5
      +/- 0.3 to 37.5 +/- 0.3 degrees C. Jugular, cisterna magna and pulmonary arterial
      blood (PAB), but not rectal temperature, were close to brain temperature during
      stable cool. The mean jugular and cisterna magna temperatures were near the brain
      temperature at 0.1 degrees C higher and 0.1 degrees C lower, respectively. No
      significant effects of hypothermia were noted on hemodynamics in any phase.
      CONCLUSION: Jugular vein temperature, along with cisterna magna and pulmonary
      artery blood and rectal temperature, reflected brain temperature during
      hypothermia. The jugular vein and cisterna magna sites more sensitively reflected
      brain temperature than other sites.

PMID- 10950320
TI  - Thiopental combination treatments for cerebral resuscitation after prolonged
      cardiac arrest in dogs. Exploratory outcome study.
AB  - We postulate that mitigating the multifactorial pathogenesis of postischemic
      encephalopathy requires multifaceted treatments. In preparation for expensive
      definitive studies, we are reporting here the results of small exploratory
      series, compared with historic controls with the same model. We hypothesized that
      the brain damage mitigating effect of mild hypothermia after cardiac arrest can
      be enhanced with thiopental loading, and even more so with the further addition
      of phenytoin and methylprednisolone. Twenty-four dogs (four groups of six dogs
      each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass
      (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with
      normothermia throughout and randomized group 2 with mild hypothermia (from
      reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental
      90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2
      treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger
      dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at
      15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All
      dogs survived. Best overall performance categories (OPC) achieved (OPC 1 =
      normal, OPC 5 = brain death) were better in group 2 than group 1 (< 0.05) and
      numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome
      (OPC 1 or 2) was achieved by all six dogs only in group 4 (P < 0.05 group 4 vs.
      2). Best NDS were 44 +/- 3% in group 1; 20 +/- 14% in group 2 (P = 0.002); 21 +/-
      15% in group 3 (NS vs. group 2); and 7 +/- 8% in group 4 (P = 0.08 vs. group 2).
      Total brain histologic damage scores (HDS) at 96 h were 156 +/- 38 in group 1; 81
      +/- 12 in group 2 (P < 0.001 vs. group 1); 53 +/- 25 in group 3 (P = 0.02 vs.
      group 2); and 48 +/- 5 in group 4 (P = 0.02 vs. group 2). We conclude that after
      prolonged cardiac arrest, the already established brain damage mitigating effect
      of mild immediate postarrest hypothermia might be enhanced by thiopental, and
      perhaps then further enhanced by adding phenytoin and methylprednisolone.

PMID- 10950321
TI  - Aspiration in chest compression alone without mechanical ventilation in the head
      down position in dogs.
AB  - BACKGROUND: Previous work by the authors has shown that chest compressions alone
      without mechanical ventilation during cardiopulmonary resuscitation in the
      natural supine position was associated with pulmonary aspiration in dogs. The
      purpose of this investigation was to test the hypothesis that a head down
      position may prevent aspiration during chest compressions alone and whether
      oxygenation can be improved by simply insufflation of oral oxygen 10 min after
      cardiac arrest. METHODS: Cardiac arrest was induced in ten mongrel dogs which
      were anesthetized and paralysed. Eight underwent chest compressions alone in
      different head down positions using an automatic compressor at 9 kg compression
      force and 3 cm compression depth. The study was composed of two parts. Part 1
      evaluated the effect of insufflation of 10 l/min O2, into the mouth of the dogs,
      10 min after initiation of resuscitation, using chest compressions alone. Part 2
      was designed to test our hypothesis that the head down position may protect the
      lungs from aspiration during chest compression alone. The mouths of the dogs were
      filled with mixed barium and the dogs underwent serial episodes of chest
      compressions, for 10 min each, in the 20 degree head down, 10 degree head down
      and the natural supine positions. Chest X-rays with antero-posterior and lateral
      views were taken to evaluate pulmonary aspiration. Two additional dogs underwent
      direct chest compression alone in the natural supine position and the time of
      chest compression was shortened to 5 min. RESULTS: All dogs in the natural
      position showed evidence of pulmonary aspiration of barium, five or six of the
      dogs showed tracheal aspiration in the 10 degree head down position, while no any
      barium was visualized in the tracheo-broncheal trees of the dogs in the 20 degree
      head down position. Supplemental oxygen in the mouth improved the mean PaO2 from
      67 +/- 26 to 160 +/- 97 mmHg during chest compressions alone. CONCLUSION: Chest
      compression alone without mechanical ventilation in the supine position caused
      pulmonary aspiration in the unprotected airway in dogs. This complication could
      be prevented by adopting a 20 degree head down position. The 10 degree head down
      position seemed to reduce the severity of the pulmonary aspiration, but not
      enough to eliminate the danger altogether. Supplemental oxygen in the mouth can
      improve oxygenation in chest compressions alone.

PMID- 10950322
TI  - Skill acquisition in resuscitation.

PMID- 10950323
TI  - A hand-held quantitative capnometer during air embolism in Gottingen mini-pigs.

PMID- 10950324
TI  - Management of the beard problem.

PMID- 10950325
TI  - Arrogance born of indifference?

PMID- 10950326
TI  - Atrial structure in the presence of visceral heterotaxy.

PMID- 10950327
TI  - Radiofrequency ablation in children.

PMID- 10950328
TI  - The Fontan procedure: analysis of cohorts and late complications.

PMID- 10950329
TI  - John Webster Kirklin: consummate cardiac surgeon and scientist.

PMID- 10950330
TI  - The diagnosis of innocent murmurs in childhood.
AB  - Innocent murmurs are common in childhood. They require accurate diagnosis to
      avoid unnecessary anxiety and/or restrictions. With this in mind, we studied
      prospectively children diagnosed by a paediatric cardiologist as having innocent
      murmurs to review the necessity of investigations in excluding organic
      abnormalities. We included 63 children in the study. The majority had the so
      called Still's, or musical/vibratory murmur. None had abnormal investigations,
      suggesting that such investigations are largely superfluous for the purpose of
      diagnosis in those patients with innocent murmurs seen by a paediatric
      cardiologist. They are often done, nonetheless, as part of the assessment and/or
      expectations of the parent or the referring physician.

PMID- 10950331
TI  - Clinical and morphologic features of perimembranous ventricular septal defect
      with overriding of the aorta--the so-called Eisenmenger ventricular septal
      defect. A study making comparisons with tetralogy of Fallot and perimembranous
      ventricular defect without aortic overriding.
AB  - The aim of our study was to elucidate the clinical and morphologic features of
      those perimembranous ventricular septal defects which extend between the
      ventricular outlets, particularly when found in association with anterior
      deviation of the muscular outlet septum and overriding of the aorta--the so
      called Eisenmenger ventricular septal defect. From 1990 through 1998, we have
      undertaken surgical correction in 203 patients with perimembranous ventricular
      septal defect. Of these, 15 patients had the Eisenmenger ventricular septal
      defect. We conducted retrospective analyses of the clinical records,
      catheterization data, and angiocardiographic and echocardiographic finding of
      these patients. Comparative studies were then made with the patients having
      tetralogy of Fallot, and those with simple perimembranous ventricular septal
      defects without overriding of the aorta. In the patients with the Eisenmenger
      ventricular septal defect, the extent of anterior deviation of the outlet septum
      was comparable with that seen in tetralogy of Fallot, but there was less
      rightward displacement of the aortic valvar orifice. In contrast to earlier
      investigators, however, we found evidence of progressive narrowing of the
      subpulmonary infundibulum in those with the Eisenmenger defect. These
      morphological features were reflected in the clinical features, since all
      patients showed evidence of increased pulmonary flow and congestive heart failure
      in early infancy, but with two-thirds of them subsequently developing right-to
      left shunting. We conclude, therefore, that the Eisenmenger ventricular septal
      defect is a discrete cardiac abnormality in which the morphologic substrate of
      anterior deviation of the outlet septum gives rise to a potential for progressive
      narrowing of the subpulmonary infundibulum. Surgical management, therefore, needs
      to take account of such narrowing as an additional cardinal morphologic feature.

PMID- 10950332
TI  - Abnormal responses for blood pressure in children and adults with surgically
      corrected aortic coarctation.
AB  - BACKGROUND: Despite successful surgical repair of aortic coarctation, life
      expectancy is reduced, and up to one-third of patients remain or become
      hypertensive. So as to characterize the responses for blood pressure, we have
      studied 55 patients with surgically repaired coarctation. Their mean age was 11.3
      +/- 5.97 years. We documented maximal uptake of oxygen, anaerobic threshold,
      plasma renin activity and blood pressures during a Bruce protocol treadmill test.
      The velocity across the site of repair as imaged by cross-sectional
      echocardiography was measured before and after exercise. We measured the changes
      in heart rate and blood pressure subsequent to an infusion of 1 ug per kg of
      isoprenalin, monitoring blood pressure over 24 hours in all patients. RESULTS:
      When compared with 40 healthy age-matched controls, the patients with coarctation
      had a normal exercise capacity. Resting systolic blood pressures above the 95th
      percentile were present in 45% of the patients. Exercise-induced hypertension,
      and an elevation in the average systolic 24 hour blood pressures, were observed,
      but less frequently than elevated baseline values, suggesting that so-called
      white-coat" hypertension may be present in this population. Abnormal reactions
      and elevation of plasma renin activity were related to a history of paradoxical
      hypertension at the time of surgery. Attenuation of the circadian rhythm for
      blood pressure was a frequent finding, and may have implications in the
      development of long-term damage to end-organs. A high correlation was found
      between mean systolic blood pressure measured by 24 hour monitoring and left
      ventricular hypertrophy (r=0.65, p<0.05). CONCLUSIONS: Abnormalities in blood
      pressure occurred independently of significant mechanical obstruction. Despite
      successful surgical repair, abnormalities in the shape of the aortic arch,
      reduced sensitivity of baroreceptor reflexes, and neurohumoral factors may all
      contribute to the development of hypertension.

PMID- 10950333
TI  - Outcomes for children with cardiomyopathy awaiting transplantation.
AB  - OBJECTIVE: To determine factors associated with outcomes after listing for
      transplantation in children with cardiomyopathies. BACKGROUND: Childhood
      cardiomyopathies form a heterogeneous group of diseases, and in many, the
      prognosis is poor, irrespective of the etiology. When profound heart failure
      develops, cardiac transplantation can be the only viable option for survival.
      METHODS: We included all children with cardiomyopathy listed for transplantation
      between 12/89 and 4/98 in this historical cohort study. RESULTS: We listed 31
      patients, 15 male and 16 female, 27 with dilated and 4 with restrictive
      cardiomyopathy, for transplantation. The median age at listing was 5.7 years,
      with a range from fetal life to 17.8 years. Transplantation was achieved in 23
      (74%), with a median interval from listing of 54 days, and a range from zero to
      11.4 years. Of the patients, 14 were transplanted within 30 days of listing. Five
      patients (16%) died before transplantation. Within the Canadian algorithm, one of
      these was in the third state, and four in the fourth state. One patient was
      removed from the list after 12 days, having recovered from myocarditis, and two
      remain waiting transplantation after intervals of 121 and 476 days, respectively.
      Patients who died were more likely to be female (5/5 vs. 11/26; p=0.04) and to
      have been in the third or fourth states at listing (5/5 vs. 15/26; p=0.04). The
      use of mechanical ventricular assistance, in 10 patients, was not a predictor of
      an adverse outcome. While not statistically significant, survival to
      transplantation was associated with treatment using inhibitors of angiotensin
      converting enzyme, less mitral regurgitation, a higher mean ejection fraction and
      cardiac index, and lower right ventricular systolic pressure. CONCLUSIONS:
      Children with cardiomyopathy awaiting transplantation have a mortality of 16%
      related to their clinical state at the time of listing.

PMID- 10950334
TI  - Clinical and electrophysiologic evolution of the Wolff-Parkinson-White syndrome
      in children: impact on approaches to management.
AB  - There is less certainty about the recommendations for radio-frequency ablation as
      a therapeutic option for Wolff-Parkinson-White syndrome in children as opposed to
      adults because of the different natural history and the age-related risks of
      ablation. To help decision-making, we evaluated the long term clinical evolution
      and electrophysiologic characteristics of pre-excitation in our series of
      children and young adults. We reviewed the clinical course of 109 patients below
      the age of 18 years who had been followed up over a period of 9+4 years, with a
      range from one to 27 years. This corresponded to 986 patient-years. We examined
      also the electrophysiologic data from 98 of those patients who underwent a
      transesophageal study. At the discovery of pre-excitation, 59% of patients were
      asymptomatic, while 29% developed supraventricular tachycardia during follow-up.
      The peak incidence of the onset of supraventricular tachycardia occurred during
      infancy. These patients had the highest incidence of subsequent spontaneous
      disappearance of the tachycardia (53%), such a favourable evolution being
      encountered in only 12% of patients in whom the abnormal rhythm first appeared
      after 12 years of age. Chronic medical treatment was required in 47% of patients,
      and proved completely effective in 45% of cases. The potential to induce atrial
      fibrillation, and the incidence pre-excitation considered to be high risk, with
      the shortest pre-excited RR interval equal to or less than 220 msec, was lowest
      in the group of patients aged less than 6 years of age, and highest in those
      older than 12 years of age (p <0.001). Pathways producing arrhythmia with high
      risk were more common in symptomatic (29%) than in asymptomatic patients (7%)
      (p<0.001). No mortality occurred. On the basis of our findings, we suggest that
      ablation should be avoided before the age of 5 or 6 years. Thereafter, the
      procedure should become the first line of treatment for symptomatic patients
      older than 12 years of age.

PMID- 10950335
TI  - Radiofrequency catheter ablation for the treatment of supraventricular
      tachycardias in children and adolescents.
AB  - We report our experience in radiofrequency catheter ablation between April, 1992
      and December, 1998, in which we treated 287 patients less than 18 years of age
      (mean 14.3 +/- 3.1 years) with supraventricular tachycardia. Accessory, pathways
      were the arrhythmic substrate in 252 of the patients (87.8%), the patients having
      a total of 265 accessory pathways. Atrioventricular nodal re-entry was the cause
      of tachycardia in 26 patients (9.0%), while atrial flutter was detected in the
      remaining 9 patients (3.1%). We were able successfully to eliminate the accessory
      pathway in 236 patients (89%), but 25 patients had recurrent arrhythmias.
      Ablation proved successful in all cases of atrioventricular node re-entry
      tachycardia, the slow pathway being ablated in 25 patients, and the fast pathway
      in only one case. Recurrence of the arrhythmia occurred in three patients
      (11.5%). We performed a second ablation in these children, all then proving
      successful. The ablation was successful in all cases of atrial flutter, with one
      recurrence (11.1%). Overall, therefore, ablation was immediately successful in
      271 patients (94.4%), with a recurrence of the arrhythmia in 29 cases (10.7%).
      The incidence of serious complications was 2.09%. There was one late death due to
      infective endocarditis, 3 patients suffered complete heart block, 1 had mild
      mitral regurgitation, and 1 patient developed an haematoma in the groin. We
      conclude that radiofrequency catheter ablation can now be considered a standard
      option for the management of paroxysmal supraventricular tachycardias in children
      and young adults.

PMID- 10950336
TI  - Successful palliation of Ebstein's malformation on the first day of life
      following fetal diagnosis.
AB  - Severe Ebstein's malformation has a poor prognosis when diagnosed during the
      neonatal period. Surgical options that have proved successful in older patients
      have been associated with high mortality and morbidity in neonates. We report
      here our success with a policy of induction at term and immediate surgical
      intervention when Ebstein's malformation was diagnosed prenatally.

PMID- 10950337
TI  - Abnormal pattern of flow in the superior caval vein in children after open heart
      surgery.
AB  - To investigate the pattern of flow in the superior caval vein in children after
      open heart surgery, we examined the flow velocity curves in 37 patients who had
      undergone surgical correction of either ventricular or atrial septal defects. The
      control group consisted of 64 age-matched children. We used pulsed Doppler
      examinations to record the velocity curves. We measured the highest and lowest
      peak flow velocities during systole and diastole, and calculated ratios for the
      various measurements. We found that the velocity of the wave in systole is lower
      than that of the wave in diastole in the postoperative patients, which is
      contrary to the normal pattern. The velocity in systole increases more than that
      in diastole during inspiration, which is also different from the normal pattern.
      The change in pattern of flow velocity curve during respiration was smaller in
      patients after surgery than in normal subjects, which might indicate that there
      is less reserve ability in the right atrium in postoperative patients.

PMID- 10950338
TI  - Arrangement of the systemic and pulmonary venous components of the atrial
      chambers in hearts with isomeric atrial appendages.
AB  - BACKGROUND: The morphological definition of atrial chambers, and the
      determination of atrial laterality, are based on analysis of the structure of the
      atrial appendages. The systemic and pulmonary venous connections to the heart,
      nonetheless, are important in the management of patients having isomeric
      appendages. In this study, therefore, we analysed the morphology of the postero
      superior walls of the atrial chambers so as to provide evidence concerning the
      morphogenetic background of those hearts, and to improve operative management.
      METHODS: We reviewed 15 autopsied specimens with isomeric right appendages, and
      10 with isomeric left appendages, paying particular attention to the morphology
      of the systemic and pulmonary venous connections. The postero-superior walls of
      the atrial chambers can be made up of the atrial body, the systemic venous
      components, or the pulmonary venous component. We analysed the contributions made
      by each of these components. RESULTS: The postero-superior walls of the atrial
      chambers were markedly variable, but could be grouped into five patterns.
      Bilaterally well-developed systemic venous components and absence of the
      pulmonary venous component within the hypoplastic atrial body were present in 9
      hearts with extracardiac pulmonary venous connections in the setting of right
      isomerism. Bilaterally well-developed systemic venous components, and a
      hypoplastic pulmonary venous component within the hypoplastic atrial body, were
      present in 5 hearts with intracardiac pulmonary venous connections in right
      isomerism. Bilaterally well-developed systemic venous components, and a
      hypoplastic pulmonary venous component within the sizable atrial body, were
      present in 1 heart with an intracardiac pulmonary venous connection in right
      isomerism. A well-developed pulmonary venous component within the atrial body,
      and hypoplasia of one systemic venous component, were present in 7 hearts with
      left isomerism. A well-developed pulmonary venous component within the atrial
      body, and hypoplasia of bilateral systemic venous components, were present in 3
      hearts with left isomerism. CONCLUSIONS: The postero-superior walls of the atrial
      chambers in hearts with isomeric atrial appendages can be analysed on the basis
      of a compound structure made of bilateral systemic venous components, a central
      pulmonary venous component, and the body of the atrium. Hearts with isomeric
      right appendages have absence or hypoplasia of the pulmonary venous component,
      while hearts with isomeric left appendages have hypoplastic systemic venous
      components.

PMID- 10950339
TI  - Aortic dissection late after repair of congenital aortic coarctation.
AB  - Aortic dissection is one of several complications that can be seen late after
      repair of aortic coarctation. We report an unusual presentation of this
      complication, and review the pertinent literature.

PMID- 10950340
TI  - Fetal echocardiographic features of twisted atrioventricular connections.
AB  - We present an example of corrected transposition with twisted discordant
      atrioventricular connections in which both fetal and postnatal echocardiograms
      were obtained. We correlate the fetal echocardiograms with the postnatal
      echocardiograms, placing emphasis on the echocardiographic clues to the diagnosis
      which were present in fetal life. The diagnosis should be suspected when the
      cardiac chambers and great arteries show an unexpected spatial relationship for
      the given segmental connections, and when the axes of opening of the
      atrioventricular valves are not parallel.

PMID- 10950341
TI  - Neuropathic pain syndrome as an occult manifestation of injury of the spinal cord
      after surgical repair of aortic coarctation.
AB  - Injury to the spinal cord injury with paraplegia, is a rare complication of
      surgical repair of aortic coarctation recognized immediately post-operatively. We
      present the case of a 41-year-old male undergoing surgery for restenosis at the
      site of a repair. Intra-operatively, he suffered inadvertent injury to an
      intercostal arterial branch during isolation of the aorta below the graft. Over
      the following months, he developed unusual symptoms involving the legs and
      genitourinary tract which, only after extensive investigations, were attributed
      to ischemic damage to the spinal cord related to the surgery. We suspect that
      similar syndromes reflecting injury to the spinal cord injury may be unrecognized
      following surgical repair of coarctation.

PMID- 10950342
TI  - Right-to-left shunt through the cardiac veins after the Fontan procedure.
AB  - We found right-to-left shunts through the cardiac veins postoperatively in 2
      patients who had undergone the Fontan procedure. In one of the patients, channels
      were present through the cardiac veins independent of the coronary sinus. In the
      other patient, an atretic orifice for the coronary sinus, coupled with a
      persistent left-sided superior caval vein, complicated the postoperative course.

PMID- 10950343
TI  - Non-confluent pulmonary arteries in a patient with pulmonary atresia and intact
      ventricular septum: ? A 5th aortic arch with a systemic-to-pulmonary arterial
      connection.
AB  - Major abnormalities of pulmonary circulation are uncommon in the patient with
      pulmonary atresia and intact ventricular septum. Non-confluent pulmonary arteries
      have only rarely been described in this setting. In this case report, we describe
      a patient in whom the pulmonary arteries are non-confluent, with the right
      pulmonary artery supplied through a right-sided arterial duct, and the left
      pulmonary artery most likely through a fifth aortic arch, thus providing a
      systemic-to-pulmonary arterial connection. We discuss the various forms of non
      confluent pulmonary arteries in the setting of pulmonary atresia and intact
      ventricular septum.

PMID- 10950344
TI  - Images in congenital heart disease. Use of 3D volume rendered magnetic resonance
      angiography to demonstrate a cervical aortic arch.

PMID- 10950345
TI  - What can we learn from numerical data?

PMID- 10950346
TI  - Deficiency of the infundibular septum in patients with interrupted aortic arch
      and del 22q11.

PMID- 10950347
TI  - A new approach for the estimation of the axial velocity using ultrasound.
AB  - The most used estimation method for calculating the blood velocity in commercial
      scanners is the autocorrelation approach. The calculation of the mean velocity
      used in this method depends on the center frequency of the interacting ultrasound
      pulse which downshifts as a function of depth, introducing a bias. A new velocity
      estimator for the mean axial velocity is presented. The estimation principle is
      based on the 2D Fourier transform and the Radon transform. The input data are a
      sequence of RF data forming a 2D data input, one column for each pulse emission.
      A 2D segment is selected for a specific depth. This data segment is first
      transformed by a 2D Fourier transform, and the result is then transformed by a
      Radon transform. The center of gravity for the angles of the lines intersecting
      the origin of the R-theta coordinate system in the Radon domain gives the mean
      axial velocity for the data segment. The benefit of this method is an estimate of
      the mean axial velocity which is independent of the center frequency of the
      propagating ultrasound pulse. The estimate will only depend on f(s) and f(pr f).
      Results of the estimation method is presented based on both simple generated RF
      harmonic data for different signal/noise ratios and simulated acoustic RF
      responses from a 3D measurement situation with an array transducer and a tube
      with plug flow. The new method shows improvement with a factor of 1.5-4 on the
      standard deviation on the estimated mean velocity for the simulated case.

PMID- 10950348
TI  - Application of different spatial sampling patterns for sparse array transducer
      design.
AB  - In the last few years, the efforts of many researchers have been focused on
      developing 3D real-time scanners. The use of 2D phased-array transducers makes it
      possible to steer the ultrasonic beam in all directions in the scanned volume. An
      unacceptably large amount of transducer channels (more than 4,000) must be used,
      if the conventional phased array transducers are extrapolated to the 2D case. To
      decrease the number of channels, sparse arrays with different aperture
      apodization functions in transmit and receive apertures have to be designed. The
      design is usually carried out in 1D, and then transferred to a 2D rectangular
      grid. In this paper, five different 2D array transducers have been considered and
      their performance was compared with respect to spatial and contrast resolution.
      An optimization of the element placement along the diagonals using vernier arrays
      is suggested. The simulation results of the ultrasound fields show a decrease in
      the grating-lobe level of 10 dB for the diagonally optimized 2D array transducers
      compared to the previously designed 2D arrays which did not consider the
      diagonals.

PMID- 10950349
TI  - Dispersion of circumferential waves on evacuated, water-loaded spherical steel
      shells.
AB  - The phase-velocity dispersion curve of the A0 Lamb wave on a free plate tends to
      zero at the vanishing frequency while on an evacuated, free spherical shell, it
      turns upward. On a fluid-loaded shell, and for the analogous circumferential A0
      wave, it again tends to zero, however, while a new A-wave (Scholte-Stoneley wave)
      which gets added due to fluid loading, is the one whose dispersion curve turns
      upward. This phenomenon is studied here for a thin stainless-steel shell on the
      basis of dispersion curves calculated from 3D elasticity theory, or obtained from
      the calculated shell resonances, and is explained by the physical nature (shell
      borne or fluid-borne) of appropriate circumferential wave portions. We also
      establish connections with the previously found partial dispersion curves.

PMID- 10950350
TI  - Surface acoustic waves at the vacuum-thermoviscoelastic solid interface.
AB  - The present investigation concerns the propagation of surface waves at the vacuum
      solid interface of a solid which is isotropic and thermoviscoelastic, i.e., for
      which the effects of heat conductivity need to be taken into account.
      Calculations show that, in addition to the Rayleigh wave, a thermal surface wave
      propagates that couples both the thermal and the elasticity effects. This latter
      wave is interpreted in terms of evanescent plane waves. The displacement field
      associated with this wave is calculated and interpreted. Some experimental
      results are also presented.

PMID- 10950351
TI  - Using acoustic emission signals for monitoring of production processes.
AB  - The systems for in-process quality assurance offer the possibility of estimating
      the workpiece quality during machining. Especially for finishing processes like
      grinding or turning of hardened steels, it is important to control the process
      continuously in order to avoid rejects and refinishing. This paper describes the
      use of on-line monitoring systems with process-integrated measurement of acoustic
      emission to evaluate hard turning and grinding processes. The correlation between
      acoustic emission signals and subsurface integrity is determined to analyse the
      progression of the processes and the workpiece quality.

PMID- 10950352
TI  - Incredible negative values of effective electromechanical coupling coefficient
      for surface acoustic waves in piezoelectrics.
AB  - The extraordinary case of increase in velocity of surface acoustic waves (SAW)
      caused by electrical shorting of the surface of the superstrong piezoelectric
      crystal potassium niobate, KNbO3, is numerically found. The explanation of this
      effect is based on considering SAWs as coupled Rayleigh and Bleustein-Gulyaev
      modes. A general procedure of approximate decoupling of the modes is suggested
      for piezoelectric crystals of arbitrary anisotropy. The effect under study takes
      place when the phase velocity of uncoupled sagittally polarized Rayleigh waves is
      intermediate between the phase velocities of uncoupled shear-horizontal Bleustein
      Gulyaev waves at the free and metallized surfaces. In this case, the
      metallization of the surface by an infinitely thin layer may cause a crossover of
      the velocity curves of the uncoupled waves. The presence of the mode coupling
      results in splitting of the curves with transition from one uncoupled branch to
      the other. This transition is responsible for the increase in SAW velocity, which
      appears to be greater than its common decrease produced by electrical shorting of
      the substrate surface.

PMID- 10950353
TI  - Numerical simulation of ultrasound-thermotherapy combining nonlinear wave
      propagation with broadband soft-tissue absorption.
AB  - Ultrasound (US) thermotherapy is used to treat tumours, located deep in human
      tissue, by heat. It features by the application of high intensity focused
      ultrasound (HIFU), high local temperatures of about 90 degrees C and short
      treating time of a few seconds. Dosage of the therapy remains a problem. To get
      it under control, one has to know the heat source, i.e. the amount of absorbed US
      power, which shows nonlinear influences. Therefore, accurate simulations are
      essential. In this paper, an improved simulation model is introduced which
      enables accurate investigations of US thermotherapy. It combines nonlinear US
      propagation effects, which lead to generation of higher harmonics, with a
      broadband frequency-power law absorption typical for soft tissue. Only the
      combination of both provides a reliable calculation of the generated heat.
      Simulations show the influence of nonlinearities and broadband damping for
      different source signals on the absorbed US power density distribution.

PMID- 10950354
TI  - The size effects of a rigid reflector in the scattering of transient ultrasonic
      field.
AB  - A model is proposed to assess the transient ultrasonic field radiated by a planar
      transducer and scattered by a target with a known dimension and geometry. The
      approach is based on the hypothesis of linear acoustics for a perfectly rigid
      reflector immersed in an isotropic, homogeneous and lossless fluid. The detected
      acoustic pressure is explained in terms of the plane and edge waves. In order to
      determine the boundary effects on the detected pressure, targets of different
      sizes were used in our simulations. An experimental verification of the proposed
      model is presented for the case of circular planar targets with different radii
      made of duralumin and immersed in distilled water. In general, the theoretically
      predicted results are in good agreement with the experimentally measured results.

PMID- 10950355
TI  - Thermally affected characterization region by Barkhausen noise.
AB  - The controlling of some industrial components require the development of new and
      particular nondestructive testing techniques. The testing method using Barkhausen
      noise (BN) is a particular one which can be applied to ferromagnetic materials.
      It is a magnetic nondestructive evaluation method and can provide very important
      information about the material structure. The aim of our work is to study the
      material structure using this technique to characterize the region submitted to
      thermal processing. Samples of steel have been heated at temperatures between 650
      degrees C and 1,200 degrees C with variable parameters (time processing,
      maintenance time, etc.). Acoustic BN processing allows an easy interpretation of
      results. Micrographs of samples have been obtained to confirm the results
      obtained by BN.

PMID- 10950356
TI  - Sex differences in opinion towards mental illness of secondary school students in
      Hong Kong.
AB  - Sex differences in social attitudes have been well documented. Women hold more
      positive attitudes toward mental illness than men do. This paper reports on the
      effect of sex differences in a study of secondary school students' opinions about
      mental illness in Hong Kong. A total of 2,223 secondary school students, drawn by
      random sample, completed a 45-item questionnaire on Opinion about Mental Illness
      in Chinese Community (OMICC) with a six-point Likert Scale. Individual items with
      weak correlations were eliminated, leaving 33 items for analysis (Cronbach's
      Alpha = .866). Using factor analysis six factors were identified. These include:
      Benevolence, Separatism, Stereotyping, Restrictiveness, Pessimistic Prediction
      and Stigmatization. Results showed that girls scored higher regarding
      benevolence. Boys were found to have more stereotyping, restrictive, pessimistic
      and stigmatizing attitudes towards mental illness.

PMID- 10950357
TI  - Utilization of psychiatric inpatient care in Greece: a nationwide study (1984
      1996).
AB  - This report examines the trends in the utilization of psychiatric inpatient care
      for the period 1984-1996, when the implementation of the psychiatric reform
      programme was initiated in Greece. Admissions in public mental hospitals declined
      by 7.2%. However discharges have been increased by 30.6% with a parallel decrease
      of the length of stay by 53.7% followed by an increase in discharges of patients
      diagnosed as suffering from schizophrenia and affective psychoses by 61.1% and
      123.8% respectively. In the private sector a remarkable reduction in both
      admissions and discharges was noticed. Admissions in psychiatric departments of
      general hospitals for the same years have been increased by 1054.1%. It seems
      that the recent deinstitutionalization process resulted in increasing trends in
      the discharges of patients suffering from psychoses. Additionally, a substantial
      increase in the number of extramural psychiatric services and rehabilitation
      places between 1994-1996 was observed. The demand for the mental health care
      services expressed as the urbanization index was found to be related with mental
      health professionals and the extramural units ratios. The higher degree of
      urbanism is, the greater the number of extramural services exist. The models
      explained variance reached 50.6%.

PMID- 10950358
TI  - Mental illness beliefs in Malaysia: ethnic and intergenerational comparisons.
AB  - Two groups of college students in Malaysia, ethnic Malay and ethnic Chinese,
      completed a mental illness attribution and help seeking questionnaire, and these
      responses were also compared with the responses of their mothers. As expected,
      ethnic Malays rated religious items, such as God and prayer, higher than the
      Chinese. However, both groups rated the social and psychological causes higher
      than religious, supernatural or physical causes. Contrary to our predictions,
      there were no intergenerational differences among either ethnic group. Medical
      pluralism was demonstrated, as a variety of apparently contradictory help seeking
      behaviors received quite high ratings including doctor/pharmacy, prayer, herbal
      medicine and traditional healers.

PMID- 10950359
TI  - Development and validation of the workshop behavior checklist: a scale for
      assessing work performance of people with severe mental illness.
AB  - The Workshop Behavior Checklist is a standardized assessment instrument to assess
      the work performance of people with severe mental illness using the situational
      assessment approach. It is modified from the Behavior Identification Form
      developed by the Material Development Center. The modification process was
      conducted by enlisting input from mental health professionals (n = 150) and
      potential employers of discharged patients with mental illness (n = 31) by
      questionnaires specially designed for this purpose. The results of these
      questionnaires were then analyzed by an expert panel consisting of 10 therapists
      and one psychiatrist working in relevant fields. Altogether 14 items in general
      behaviors, vocational behaviors, and social behaviors were selected. In addition,
      a new version of the checklist together with its rating guidelines were designed.
      Exploratory factor analysis (n = 112) shows that all 14 items fit well into a
      four-factor model explaining 67.2% of total variance, which is in line with the
      original design of the revised checklist. Cronbach alpha analysis shows that the
      revised checklist has acceptable to very good internal consistency (.51 to .84)
      and intraclass correlation coefficients indicate that it has good to excellent
      inter-rater (.57 to .81) and test-retest (.86 to .94) reliability. Clinical
      implications and further research are discussed.

PMID- 10950360
TI  - Cultural sensitivity training in mental health: treatment of Orthodox Jewish
      psychiatric inpatients.
AB  - We describe some of the cultural/religious issues which arose in the treatment of
      major psychiatric disorders among Orthodox Jewish inpatients at SUNY Health
      Science Center's University Hospital (SUH) in Brooklyn, New York. The distinct
      ways in which cultural and religious factors impacted on presentation,
      therapeutic interventions, and transference-countertransference reactions are
      noted. Specific reference is made to the use of religion by patients and families
      as a means of defense, rationalization or power-brokering. Via case vignettes, we
      explore ways of distinguishing between culturally appropriate vs. maladaptive
      behaviors in the Orthodox population. Practical solutions are suggested for
      sensitive ways to surmount culture-based barriers to effective inpatient therapy
      in this group.

PMID- 10950361
TI  - How stigmatising is schizophrenia in India?
AB  - Stigma is a social devaluation of a person because of personal attribute leading
      to an experience of sense of shame, disgrace and social isolation. The nature of
      stigma in schizophrenia and its relationship to attribution was studied in one
      hundred and fifty-nine urban patients of Madras, India who fulfilled DSM-IV
      criteria for schizophrenia. The response of the primary care givers to fourteen
      questions on stigma and 14 on what they thought attributed to the illness was
      elicited. Based on the mean stigma score, the entire sample was divided into two
      groups- those with high and low stigma. Marriage, fear of rejection by neighbour,
      and the need to hide the fact from others were some of the more stigmatising
      aspects. Many care givers reported feelings of depression and sorrow.
      Discriminant function analysis showed that female sex of the patient and a
      younger age of both patient and caregiver were related to higher stigma. Among
      attribution items, having no explanation to offer, and attributions to faulty
      biological functioning, character of life style, substance abuse and intimate
      interpersonal relationship discriminated between the two groups. The relevance of
      stigma in the cultural context is described.

PMID- 10950362
TI  - Factor structure of the Mental Health Professionals Stress Scale (MHPSS) among
      clinical psychologists in India.
AB  - This study examined the factor structure of the Mental Health Professionals
      Stress Scale (MHPSS) and its reliability and validity in a sample of 116 clinical
      psychologists in India. Principal component analysis of the MHPSS identified four
      factors that accounted for 42.2% of the total variance. These 4 factors reflected
      6 of the 7 original subscales. The subscale 'Client-related difficulties' did not
      emerge as a distinct factor. The authors attribute this to cultural differences
      in the therapist-patient relationship. The MHPSS correlated negatively with
      measures of professional role satisfaction and subjective well being. It was
      concluded that the MHPSS is a reliable and valid tool to measure sources of
      occupational stress experienced by mental health professionals.

PMID- 10950364
TI  - Acquired immunodeficiency syndrome malignancies.

PMID- 10950363
TI  - What choices are available for treatment of the patient with chronic lymphocytic
      leukemia who is fludarabine-refractory?

PMID- 10950366
TI  - Transplantation-related lymphoproliferative disorder: a model for human
      immunodeficiency virus-related lymphomas.
AB  - Post-transplant lymphoproliferative disorders (PTLD) share many of the features
      of human immunodeficiency virus (HIV)-related lymphomas, although important
      differences exist. PTLD ranges from hyperplastic lesions to aggressive lymphoma
      or multiple myeloma histology. The coexistence of multiple clones, and the strong
      association with the Epstein-Barr virus (EBV), represent a uniquely different
      mechanism for lymphomagenesis when compared with de novo lymphoma. The risk of
      PTLD increases as the duration of immunodeficiency lengthens, with unusual, newly
      described entities arising after prolonged immunosuppression. The risk is also
      strongly influenced by the specific anti-T-cell therapies used to prevent graft
      rejection, providing insight into the nature of immune surveillance. The presence
      or absence of bcl-6 mutations may be predictive of the reversibility of the PTLD
      with reduction in immunosuppressive therapy. The use of cytotoxic agents has been
      complicated by problems similar to those encountered with HIV-related lymphomas,
      but can nonetheless be very effective. Long-term remission has been achieved with
      anti-CD21 and anti-CD24 antibodies, although these have not been equally
      effective for all categories of PTLD. In vitro-expanded EBV-specific T cells have
      been effective both as treatment and as prophylaxis in the setting of PTLD
      occurring after marrow transplantation. EBV viral load measurement correlates
      with the emergence of PTLD, and may make clinical trials of screening,
      prophylaxis, or early intervention possible.

PMID- 10950365
TI  - The epidemiology of acquired immunodeficiency syndrome malignancies.
AB  - The acquired immunodeficiency syndrome (AIDS) results in an extraordinary
      increase in the risk of two malignancies: Kaposi's sarcoma (KS; relative risk
      [RR], >10,000) and B-cell non-Hodgkin's lymphoma (NHL; RR, >100). KS appears to
      result from uncontrolled expression of latency genes of human herpes virus-8 (HHV
      8). KS is exquisitely sensitive to immune deficiency, and its incidence has
      declined during the late 1990s with the advent of highly active antiretroviral
      therapy (HAART) against human immunodeficiency virus (HIV). The risk of NHL is
      highest with high-grade histologies, and the incidence has declined only slightly
      with HAART. The risk of KS and NHL is decreased for people with the CCRS delta32
      polymorphism, and NHL risk is increased with the SDFI-3'A polymorphism. Children
      with AIDS have a similar pattern of risk, but also have a high risk of
      leiomyosarcoma (RR, approximately 10,000). AIDS-related immune deficiency also
      increases the risk of Hodgkin's disease (RR, 8), probably multiple myeloma (RR,
      5), and possibly other tumors in adults. Although the occurrence of cervical
      cancer (RR, 3) and anal cancer (RR, 30) is excessive among persons with AIDS,
      most or all of this excess results from sexually acquired human papillomavirus
      (HPV) infection and not from immune deficiency. Future efforts need to focus on
      understanding how the immune perturbation of AIDS results in a limited spectrum
      of tumors and most urgently on controlling the underlying HIV epidemic.

PMID- 10950367
TI  - Kaposi's sarcoma-associated herpes virus and acquired immunodeficiency syndrome
      related malignancy.
AB  - Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus
      8 (HHV-8), is a recently described gamma-herpes virus that has been etiologically
      linked to two different acquired immunodeficiency syndrome (AIDS)-related
      malignancies by strong epidemiologic and pathologic evidence. Infection been
      shown to precede and predict the development of Kapasi's sarcoma (KS) in human
      immunodeficiency virus (HIV)-infected patients, and viral DNA has been found in
      KS lesions of all types and stages. Furthermore, KSHV is a lymphotropic virus and
      is present in nearly all cases of primary effusion lymphoma, a rare malignancy
      disproportionately affecting HIV-infected individuals. KSHV is also thought to
      dramatically affect the incidence, type, and course of multicentric Castleman's
      disease, another lymphoproliferative disorder over-represented in people with
      AIDS. KSHV encodes many potentially oncogenic products, including several
      apparently pirated from the human genome. These include various chemokines, cell
      cycle regulatory proteins, and survival and proliferation factors. Knowledge is
      rapidly accumulating concerning the viral pathogenic mechanisms and host
      cofactors necessary for KSHV-mediated disease.

PMID- 10950368
TI  - The role of human immunodeficiency virus-I in the pathogenesis of acquired
      immunodeficiency syndrome-related Kaposi's sarcoma: the importance of an
      inflammatory and angiogenic milieu.
AB  - People infected with human immunodeficiency virus type-I (HIV-I) have an
      increased incidence of Kaposi's sarcoma (KS) and HIV-I infection alters the
      natural history of KS. The potent trans-activator HIV-I protein Tat plays a major
      role in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS.
      Among many of its KS-promoting activities, the Tat protein augments the
      angiogenic activities of basic fibroblast growth factor (bFGF), interferon gamma,
      and vascular endothelial growth factor (VEGF); it also mimics the effects of the
      extramedullary matrix proteins fibronectin and vitronectin, and increases the
      expression of matrix metalloproteinases. Inflammatory cytokines induce
      endothelial cells to acquire the phenotype and functional features of AIDS
      related KS spindle cells. These cytokines act by both autocrine and paracrine
      mechanisms. The synergy between cytokines and the HIV-I Tat protein provides
      possible insight into why AIDS-related KS is more aggressive than the classic
      Mediterranean form, in which the HIV-I Tat protein does not play a role.

PMID- 10950369
TI  - Acquired immunodeficiency syndrome-related Kaposi's sarcoma: clinical features,
      staging, and treatment.
AB  - The clinical course of acquired immunodeficiency syndrome (AIDS)-related Kaposi's
      sarcoma (KS) is highly variable, ranging from minimal stable disease to explosive
      growth. Although KS is primarily a cutaneous disease, extracutaneous spread is
      common; the oral cavity, gastrointestinal (GI) tract, lungs, and lymph nodes are
      often involved. The psychosocial burden associated with KS may be profound. The
      initial evaluation of a patient with KS consists mainly of a thorough physical
      examination with special attention paid to those areas typically affected by the
      disease, the testing of stool for occult blood, and a chest x-ray. Treatment
      options depend greatly on the tumor (extent of tumor and rate of growth), human
      immunodeficiency virus type I (HIV-I) viral load, and host factors (CD4+ T
      lymphocyte count and overall medical condition). Limited cutaneous disease may be
      treated with topical alitretinoin gel, intralesional vinblastine, radiation
      therapy, laser therapy, or cryotherapy. The high benefit-to-risk ratio of
      liposomal anthracyclines (daunorubicin and doxorubicin) and paclitaxel have
      tremendously simplified the management of patients in whom systemic therapy is
      warranted. Additionally, epidemiologic evidence of a marked decline in new KS
      since the widespread use of highly active antiretroviral therapy (HAART)
      advocates its use. KS herpes virus/human herpes virus 8 (KSHV/HHV-8), sex
      hormones, and the processes of angiogenesis and cellular differentiation all
      serve as targets for pathogenesis-based clinical trials. Virtually all patients
      with KS can benefit from the many approved and investigational agents developed
      through years of collaborative translational and clinical research.

PMID- 10950370
TI  - The molecular basis of acquired immunodeficiency syndrome-related
      lymphomagenesis.
AB  - Acquired immunodeficiency syndrome (AIDS)-related lymphomas consistently display
      a B-cell phenotype and are histogenetically related to germinal center (GC) or
      post-GC B cells in the overwhelming majority of cases. The pathogenesis of AIDS
      related lymphoma is a multistep process involving factors provided by the host,
      as well as alterations intrinsic to the tumor one. Host factors involved in AIDS
      related lymphomagenesis include reduced immunosurveillance particularly against
      Epstein-Barr virus (EBV)-infected B cells, human immunodeficiency virus (HIV)
      induced alteration of endothelial functions, B-cell stimulation and selection by
      antigen, HIV-induced deregulation of several cytokine loops, and possibly the
      host's genetic background. The molecular pathways of viral infection and lesions
      of cancer related genes associated with AIDS-related lymphoma vary substantially
      in different clinicopathologic categories of the disease and highlight the marked
      degree of biological heterogeneity of these lymphomas. Although the reasons for
      the heterogeneity of AIDS-related lymphoma are not totally clear, it is generally
      believed that the host's background selects for which specific molecular pathway
      of AIDS-related lymphoma is activated in a given patient.

PMID- 10950371
TI  - Acquired immunodeficiency syndrome-related lymphoma: clinical aspects.
AB  - While the widespread use of highly active antiretroviral therapy (HAART) has led
      to substantial decreases in the incidence of opportunistic infections and
      Kaposi's sarcoma, a major decrease in lymphoma has not yet occurred. Patients
      with acquired immunodeficiency syndrome (AIDS)-related lymphoma present with
      widespread, extranodal disease, often in the presence of systemic "B" symptoms.
      Factors associated with decreased survival include age greater than 35 years,
      history of injection drug use, poor performance status, CD4 cell count less than
      100/dL, a history of AIDS prior to the diagnosis of lymphoma, stage III or IV
      disease, and/or elevated lactate dehydrogenase (LDH) levels. Low-dose combination
      chemotherapy has been associated with complete remission (CR) rates of 41% to
      46%, with an overall median survival time of 8.7 months, similar to results
      achieved with standard-dose therapy, which is associated with greater toxicity.
      Infusional regimens have been associated with CR rates as high as 94%, and
      further evaluation is justified. Combination chemotherapy may be given safely
      with HAART. Treatment of relapsed AIDS-related lymphoma remains problematic.

PMID- 10950372
TI  - Acquired immunodeficiency syndrome-related lymphomas: future directions.
AB  - Despite some exciting new leads, human immunodeficiency virus-I (HIV-I)-related
      non-Hodgkin's lymphoma (HIV-NHL) remains a fatal malignancy for the vast majority
      of patients. The use of highly active antiretroviral therapy (HAART) has not
      produced a fall in the incidence of HIV-NHL and conventional cytotoxic
      chemotherapy is associated with a negligible cure rate. New treatment options are
      needed. Future therapeutic directions in HIV-NHL should be based on a better
      understanding of three fundamental aspects of lymphomagenesis in the setting of
      acquired immunodeficiency. (I) New information on the molecular and pathological
      heterogeneity of HIV-NHL should be applied to the development of risk-adapted
      therapy. The identification of patient subsets with different susceptibility to
      cytotoxic chemotherapy, immunomodulation, or antiviral strategies is essential
      for the design of clinical trials of investigational new agents in HIV-NHL. (2)
      Known viral pathogens need to be better understood. The presence and role of new
      viruses should be investigated. Key biological interactions between virus and
      host, mediated by oncogenic, immunomodulatory, and antiapoptotic viral proteins,
      should become the main target for new drug development. (3) Immune reconstitution
      with HAART and immunostimulatory cytokines such as interleukin-2 (IL-2) and IL
      12, combined with drugs that downregulate the replication or gene expression of
      tumor-associated viruses such as Epstein-Barr virus (EBV) and human herpes virus
      8 (HHV-8), possibly in combination, should remain a primary goal in the treatment
      of HIV-NHL. Preventive immunization, using autologous tumor cell vaccines or
      antigen-specific cellular adoptive immunotherapy should be explored.

PMID- 10950373
TI  - Invasive and preinvasive cervical neoplasia in human immunodeficiency virus
      infected women.
AB  - An association between human immunodeficiency virus (HIV) infection and cervical
      neoplasia in women has recently been recognized. Cervical cancer was designated
      as a diagnostic criteria for acquired immunodeficiency syndrome (AIDS) in HIV
      infected women in 1993. The two conditions share a number of risk factors,
      including a history of multiple sexual partners and disproportionate effect on
      younger women and ethnic minorities. HIV appears to accelerate the pathogenesis
      of cervical neoplasia at the molecular level, although clinical evidence of
      disease progression is limited. The optimal strategy for screening HIV-infected
      women for cervical neoplasia is unclear, but should include at least an annual
      Papanicolaou (Pap) smear. Preinvasive cervical neoplasia in HIV-infected women
      should be treated with standard excisional/ ablative therapy, followed by vaginal
      5-flourouracil cream. Invasive cervical cancer should be treated with standard
      surgical therapy or radiotherapy. Recurrence rates are high following treatment
      of either invasive or preinvasive disease, but are reduced in women undergoing
      highly active antiretroviral therapy.

PMID- 10950374
TI  - Anal squamous intraepithelial lesions in human immunodeficiency virus-positive
      men and women.
AB  - Studies from the era prior to the introduction of highly active antiretroviral
      therapy (HAART) have shown that the prevalence of anal human papillomavirus (HPV)
      infection and anal squamous intraepithelial lesions (ASIL) was very high among
      human immunodeficiency virus (HIV)-positive homosexual men, and to a lesser
      extent, among HIV-negative homosexual men. Prospective data also show that the
      incidence of high-grade ASIL (HSIL), the putative invasive cancer precursor
      lesion, was high among both HIV-positive and HIV-negative men. Studies of HIV
      positive women and HIV-negative women at high risk of HIV show a high prevalence
      of anal HPV infection and ASIL. Early data suggest that most anal HSIL lesions do
      not regress after an individual begins HAART. Since progression of anal HSIL to
      invasive anal cancer may require several years, the improvement in survival
      associated with HAART may paradoxically lead to an increased risk of anal cancer.
      Consistent with this, the incidence of invasive anal cancer has been increasing
      over the last few years among HIV-positive gay men, and is now approximately
      twice that of HIV-negative gay men. The potential to prevent anal cancer through
      detection and treatment of anal HSIL suggests a need to screen high-risk
      individuals with anal cytology, similar to the longstanding cervical cytology
      screening program currently used to prevent cervical cancer. Cost-effectiveness
      analyses indicate that anal screening programs should be cost-effective in HIV
      positive men. However, barriers to implementation of screening preclude near-term
      implementation of such a program. These include an inadequate number of
      clinicians skilled in diagnosis and treatment of HSIL and lack of effective
      medical alternatives to surgical excision. Efforts are underway to address these
      issues and to better understand the natural history of ASIL in the HAART era.

PMID- 10950375
TI  - Human immunodeficiency virus-associated Hodgkin's disease.
AB  - Hodgkin's disease represents the most common type of non-acquired
      immunodeficiency virus (AIDS)-defining tumor that occurs in the human
      immunodeficiency virus (HIV)-positive population. More than 300 cases of
      Hodgkin's disease in HIV-infected individuals have been reported, mainly from the
      European countries (ie, Italy, Spain, and France) and to a lesser extent from the
      United States. All series have documented unusually aggressive tumor behavior,
      including a higher frequency of unfavorable histologic subtypes, advanced stages,
      and poorer therapeutic outcome, as compared with the behavior of Hodgkin's
      disease outside of the HIV setting.

PMID- 10950376
TI  - Functional differentiation of multiple perilesional zones after focal cerebral
      ischemia.
AB  - Transient and permanent focal cerebral ischemia results in a series of typical
      pathophysiologic events. These consequences evolve in time and space and are not
      limited to the lesion itself, but they can be observed in perilesional (penumbra)
      and widespread ipsi- and sometimes contralateral remote areas (diaschisis). The
      extent of these areas is variable depending on factors such as the type of
      ischemia, the model, and the functional modality investigated. This review
      describes some typical alterations attributable to focal cerebral ischemia using
      the following classification scheme to separate different lesioned and
      perilesional areas: (1) The lesion core is the brain area with irreversible
      ischemic damage. (2) The penumbra is a brain region that suffers from ischemia,
      but in which the ischemic damage is potentially, or at least partially,
      reversible. (3) Remote brain areas are brain areas that are not directly affected
      by ischemia. With respect to the etiology, several broad categories of remote
      changes may be differentiated: (3a) remote changes caused by brain edema; (3b)
      remote changes caused by waves of spreading depression; (3c) remote changes in
      projection areas; and (3d) remote changes because of reactive plasticity and
      systemic effects. The various perilesional areas are not necessarily homogeneous;
      but a broad differentiation of separate topographic perilesional areas according
      to their functional state and sequelae allows segregation into several signaling
      cascades, and may help to understand the functional consequences and adaptive
      processes after focal brain ischemia.

PMID- 10950377
TI  - Cortical neurogenesis in adult rats after reversible photothrombotic stroke.
AB  - Neurogenesis occurs throughout life in the dentate gyrus of hippocampus and
      subventricular zone, but this phenomenon has rarely been observed in other brain
      regions of adult mammals. The aim of the current study was to investigate the
      cell proliferation process in the ischemically challenged region-at-risk after
      focal cerebral ischemia in the adult rat brain. A reversible photothrombotic ring
      stroke model was used, which features sustained hypoperfusion followed by late
      spontaneous reperfusion and a remarkable morphologic tissue recovery in the
      anatomically well defined somatosensory cortical region-at-risk. Twelve-week-old
      male Wistar rats received repeated intraperitoneal injections of the cell
      proliferation specific marker 5-bromodeoxyuridine (BrdU) after stroke induction.
      Immunocytochemistry of coronal brain sections revealed that the majority of BrdU
      positive cells were of glial, macrophage, and endothelial origin, whereas 3% to
      6% of the BrdU-positive cells were double-labeled by BrdU and the neuronspecific
      marker Map-2 at 7 and 100 days after stroke onset in the region-at-risk. They
      were distributed randomly in cortical layers II-VI. Three-dimensional confocal
      analyses of BrdU and the neuronal-specific marker Neu N by double
      immunofluorescence confirmed their colocalization within the same cells at 72
      hours and 30 days after stroke induction. This study suggests that, as a
      potential pathway for brain repair, new neurons can be generated in the cerebral
      cortex of adult rats after sublethal focal cerebral ischemia.

PMID- 10950378
TI  - Altered central nervous system cytokine-growth factor expression profiles and
      angiogenesis in metallothionein-I+II deficient mice.
AB  - To study the importance of metallothionein-I and -II (MT-I+II) for brain
      inflammation and regeneration, the authors examined normal and MT-I+II knock-out
      (MT-KO) mice subjected to a cortical freeze injury. Normal mice showed profound
      neurodegeneration, inflammation, and gliosis around the injury, which was
      repaired by 20 days postlesion (dpl). However, in MT-KO mice the lesion
      associated inflammation was still present as late as 90 dpl. Scanning electron
      microscopy demonstrated that the number of capillaries was lower, and
      ultrastructural preservation of the lesioned parenchyma was poorer in MT-KO mice,
      suggesting an altered angiogenesis. To gain insight into the mechanisms involved,
      a number of cytokines and growth factors were evaluated. The number of cells
      expressing the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha was higher
      in MT-KO mice than in normal mice, which was confirmed by RNase protection
      analysis, whereas the number of cells expressing the growth factors bFGF,
      TGFbeta1, VEGF, and NT-3 was lower. Increased expression of proinflammatory
      cytokines could be involved in the sustained recruitment of CD-14+ and CD-34+
      inflammatory cells and their altered functions observed in MT-KO mice. Decreases
      in trophic factors bFGF, TGFbeta1, and VEGF could mediate the decreased
      angiogenesis and regeneration observed in MT-KO mice after the freeze lesion. A
      role for MT-I+II in angiogenesis was also observed in transgenic mice expressing
      IL-6 under the control of the promoter of glial fibrillary acidic protein gene
      (GFAP-IL6 mice) because MT-I+II deficiency dramatically decreased the IL-6
      induced angiogenesis of the GFAP-IL6 mice. In situ hybridization analysis
      indicated that the MT-III expression was not altered by MT-I+II deficiency. These
      results suggest that the MT-I+II isoforms have major regulatory functions in the
      brain inflammatory response to injury, especially in the angiogenesis process.

PMID- 10950379
TI  - Increase in endogenous brain superoxide dismutase as a potential mechanism of
      lipopolysaccharide-induced brain ischemic tolerance.
AB  - A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before
      60-minute middle cerebral artery occlusion, induced a delayed neuroprotection
      proven by the significant decrease (-35%) of brain infarct volume in comparison
      with control, whereas infarct volumes remained unchanged in rats treated 12, 24,
      or 168 hours before ischemia. This delayed neuroprotective effect of LPS was
      induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared
      with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in
      the cortical part of the infarcted zone, not in the subcortical part. The
      beneficial effect of LPS on consequences of middle cerebral artery occlusion was
      suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/ kg) administered 1
      hour before LPS, whereas both drugs had no direct effect on infarct volume by
      themselves, suggesting that activation of inflammatory pathway is involved in the
      development of LPS-induced brain ischemic tolerance. Preadministration of
      cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain
      ischemic tolerance suggesting that a protein synthesis is also necessary as a
      mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized
      proteins because lipopolysaccharide increased SOD brain activity 72 hours, but
      not 12 hours, after its administration, which paralleled the development of brain
      ischemic tolerance. In contrast, catalase brain activity remained unchanged after
      LPS administration. The LPS-induced delayed increase in SOD brain content was
      suppressed by a previous administration of indomethacin. These data suggest that
      the delayed neuroprotective effect of low doses of LPS is mediated by an
      increased synthesis of brain SOD that could be triggered by activation of
      inflammatory pathway.

PMID- 10950380
TI  - The novel beta-blocker, carvedilol, provides neuroprotection in transient focal
      stroke.
AB  - Increasing evidence supports a role for oxidative stress, proinflammatory
      cytokines, and apoptosis in the pathophysiology of focal ischemic stroke.
      Previous studies have found that the multi-action drug, carvedilol, is a mixed
      adrenergic antagonist, and that it behaves as an antioxidant and inhibits
      apoptosis. In the current study, the authors investigated whether carvedilol
      provides protection in focal cerebral ischemia and whether this protection is
      associated with reduced apoptosis and the downregulation of the inflammatory
      cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin- 1beta (IL
      1beta). Male Sprague-Dawley rats were subjected to transient middle cerebral
      artery occlusion (MCAO) by an intraluminal filament technique. Carvedilol (1, 3,
      and 10 mg/kg) was injected daily subcutaneously 2 or 4 days before the induction
      of ischemia. Neurologic scores, infarct volumes, TUNEL staining, and mRNA levels
      of TNF-alpha and IL-1beta were assessed at 24 hours reperfusion. The effect of
      carvedilol on microvascular cortical perfusion was studied with continuous laser
      Doppler flowmetry. Twenty-four hours after MCAO, carvedilol at all three doses
      reduced infarct volumes by at least 40% and reduced neurologic deficits on
      average by 40% compared with vehicle-treated controls when given 2 or 4 days
      before the induction of ischemia. This protection was not mediated by changes in
      temperature or blood flow. Treatment with all three dose regimens resulted in
      fewer TUNEL positive cells compared with controls. At 24 hours reperfusion,
      carvedilol decreased TNF-alpha and IL-1beta expression by 40% to 50% in the
      ipsilateral ischemic cortex compared with the contralateral controls. The results
      of the current study indicate that carvedilol is neuroprotective in focal
      cerebral ischemia and may protect the ischemic brain by inhibiting apoptosis and
      attenuating the expression of TNF-alpha and IL-1beta.

PMID- 10950381
TI  - Immunohistochemical localization of the VIP1 receptor (VPAC1R) in rat cerebral
      blood vessels: relation to PACAP and VIP containing nerves.
AB  - The two structurally related peptides, vasoactive intestinal polypeptide (VIP)
      and pituitary adenylate cyclase activating polypeptide (PACAP), are present in
      cerebral vascular nerve fibers. Biologic actions of VIP are exerted through two
      receptors, VPAC1 and VPAC2, having similar binding affinity for both VIP and
      PACAP. In the current study, the authors have developed a specific antibody
      against the rVPAC1 receptor to examine the localization of rVPAC1
      immunoreactivity in cerebral arteries and arterioles of the rat by
      immunohistochemistry using fluorescence confocal microscopy. Specificity of the
      antiserum was ensured by immunoblotting and immunocytochemistry of cells
      transfected with cDNA encoding the different PACAP-VIP receptor subtypes. The
      rVPAC1 receptor immunoreactivity was localized to the plasmalemma of circularly
      orientated smooth muscle cells on superficial cerebral arteries and arterioles
      taken from the basal surface of the brain. By double immunostaining VIP
      immunoreactive nerve fibers and, to a lesser extent, those containing PACAP were
      shown to have intimate contact with the receptor protein. Vasoactive intestinal
      polypeptide and PACAP containing cerebrovascular nerve fibers were found in
      separate nerve populations with different distribution pattern and density. In
      brain sections processes of cortical VIP-, but not PACAP-, containing neurons
      seemed to innervate the rVPAC1 receptor of pial arterioles on the brain surface.
      The current findings provide the neuroanatomical substrate for a role of VIP and
      maybe PACAP in the regulation of cerebral blood flow.

PMID- 10950382
TI  - Coupling of cerebral blood flow and oxygen metabolism in infant pigs during
      selective brain hypothermia.
AB  - Studies documenting the cerebral hemodynamic consequences of selective brain
      hypothermia (SBH) have yielded conflicting data. Therefore, the authors have
      studied the effect of SBH on the relation of cerebral blood flow (CBF) and CMRO2
      in the forebrain of pigs. Selective brain hypothermia was induced in seven
      juvenile pigs by bicarotid perfusion of the head with extracorporally cooled
      blood. Cooling and stepwise rewarming of the brain to a Tbrain of 38 degrees C,
      25 degrees C, 30 degrees C, and 38 degrees C at normothermic Ttrunk (38 degrees
      C) decreased CBF from 71 + 12 mL 100 g(-1) min(-1) at normothermia to 26+/-3 mL
      100 g(-1) min(-1) and 40+/-12 mL 100 g(-1) min(-1) at a Tbrain of 25 degrees C
      and 30 degrees C, respectively. The decrease of CMRO2 during cooling of the brain
      to a Tbrain of 25 degrees C resulted in a mean Q10 of 2.8. The ratio between CBF
      and CMRO2 was increased at a Tbrain of 25 degrees C indicating a change in
      coupling of flow and metabolism. Despite this change, regional perfusion remained
      coupled to regional temperatures during deep cerebral hypothermia. The data
      demonstrate that SBH decreases CBF and oxygen metabolism to a degree comparable
      with the cerebrovascular and metabolic effects of systemic hypothermia. The
      authors conclude that, irrespective of a change in coupling of blood flow and
      metabolism during deep cerebral hypothermia, cerebral metabolism is a main
      determinant of CBF during SBH.

PMID- 10950383
TI  - Quantitative measurements of cerebral blood oxygen saturation using magnetic
      resonance imaging.
AB  - A quantitative estimate of cerebral blood oxygen saturation is of critical
      importance in the investigation of cerebrovascular disease because of the fact
      that it could potentially provide information on tissue viability in vivo. In the
      current study, a multi-echo gradient and spin echo magnetic resonance imaging
      sequence was used to acquire images from eight normal volunteer subjects. All
      images were acquired on a Siemens 1.5T Symphony whole-body scanner (Siemens,
      Erlangen, Germany). A theoretical signal model, which describes the signal
      dephasing phenomena in the presence of deoxyhemoglobin, was used for
      postprocessing of the acquired images and obtaining a quantitative measurement of
      cerebral blood oxygen saturation in vivo. With a region-of-interest analysis, a
      mean cerebral blood oxygen saturation of 58.4%+/-1.8% was obtained in the brain
      parenchyma from all volunteers. It is in excellent agreement with the known
      cerebral blood oxygen saturation under normal physiologic conditions in humans.
      Although further studies are needed to overcome some of the confounding factors
      affecting the estimates of cerebral blood oxygen saturation, these preliminary
      results are encouraging and should open a new avenue for the noninvasive
      investigation of cerebral oxygen metabolism under different pathophysiologic
      conditions using a magnetic resonance imaging approach.

PMID- 10950384
TI  - Quantitation of regional cerebral blood flow corrected for partial volume effect
      using O-15 water and PET: II. Normal values and gray matter blood flow response
      to visual activation.
AB  - One of the most limiting factors for the accurate quantification of physiologic
      parameters with positron emission tomography (PET) is the partial volume effect
      (PVE). To assess the magnitude of this contribution to the measurement of
      regional cerebral blood flow (rCBF), the authors have formulated four kinetic
      models each including a parameter defining the perfusable tissue fraction (PTF).
      The four kinetic models used were 2 one-tissue compartment models with (Model A)
      and without (Model B) a vascular term and 2 two-tissue compartment models with
      fixed (Model C) or variable (Model D) white matter flow. Furthermore, rCBF based
      on the autoradiographic method was measured. The goals of the study were to
      determine the following in normal humans: (1) the optimal model, (2) the optimal
      length of fit, (3) the model parameters and their reproducibility, and (4) the
      effects of data acquisition (2D or 3D). Furthermore, the authors wanted to
      measure the activation response in the occipital gray matter compartment, and in
      doing so test the stability of the PTF, during perturbations of rCBF induced by
      visual stimulation. Eight dynamic PET scans were acquired per subject (n = 8),
      each for a duration of 6 minutes after IV bolus injection of H2(15)O. Four of
      these scans were performed using 2D and four using 3D acquisition. Visual
      stimulation was presented in four scans, and four scans were during rest. Model C
      was found optimal based on Akaike's Information Criteria (AIC) and had the
      smallest coefficient of variance after a 6-minute length of fit. Using this model
      the average PVE corrected rCBF during rest in gray matter was 1.07 mL x min(-1) x
      g(-1) (0.11 SD), with an average coefficient of variance of 6%. Acquisition mode
      did not affect the estimated parameters, with the exception of a significant
      increase in the white matter rCBF using the autoradiographic method (2D: 0.17 mL
      x min(-1) x g(-1) (0.02 SD); 3D: 0.21 mL x min(-1) x g(-1) (0.02 SD)). At a 6
      minute fit the average gray matter CBF using Models C and D were increased by
      100% to 150% compared with Models A and B and the autoradiographic method. There
      were no significant changes in the perfusable tissue fraction by the activation
      induced rCBF increases. The largest activation response was found using Model C
      (median = 39.1%). The current study clearly demonstrates the importance of PVE
      correction in the quantitation of rCBF in normal humans. The potential use of
      this method is to cost-effectively deliver PVE corrected measures of rCBF and
      tissue volumes without reference to imaging modalities other than PET.

PMID- 10950385
TI  - Regional differences in cerebral vascular response to PaCO2 changes in humans
      measured by positron emission tomography.
AB  - Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction,
      respectively. However, regional differences in the vascular response to changes
      in Paco2 in the human brain are not pronounced. In the current study, these
      regional differences were evaluated. In each of the 11 healthy subjects, cerebral
      blood flow (CBF) was measured using 15O-water and positron emission tomography at
      rest and during hypercapnia and hypocapnia. All CBF images were globally
      normalized for CBF and transformed into the standard brain anatomy. t values
      between rest and hypercapnia or hypocapnia conditions were calculated on a pixel
      by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant
      relative hyperperfusion during hypercapnia was observed, indicating a large
      capacity for vasodilatation. In the pons and putamen, a significant relative
      hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction,
      was also observed, indicating marked vascular responsiveness. In the temporal,
      temporo-occipital, and occipital cortices, significant relative hypoperfusion
      during hypercapnia and significant relative hypoperfusion during hypocapnia were
      observed, indicating that cerebral vascular tone at rest might incline toward
      vasodilatation. Such regional heterogeneity of the cerebral vascular response
      should be considered in the assessment of cerebral perfusion reserve by
      hypercapnia and in the correction of CBF measurements for variations in subjects'
      resting Paco2.

PMID- 10950386
TI  - Quantitation of regional cerebral blood flow corrected for partial volume effect
      using O-15 water and PET: I. Theory, error analysis, and stereologic comparison.
AB  - Limited spatial resolution of positron emission tomography (PET) can cause
      significant underestimation in the observed regional radioactivity concentration
      (so-called partial volume effect or PVE) resulting in systematic errors in
      estimating quantitative physiologic parameters. The authors have formulated four
      mathematical models that describe the dynamic behavior of a freely diffusible
      tracer (H215O) in a region of interest (ROI) incorporating estimates of regional
      tissue flow that are independent of PVE. The current study was intended to
      evaluate the feasibility of these models and to establish a methodology to
      accurately quantify regional cerebral blood flow (CBF) corrected for PVE in
      cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O
      two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on
      structural magnetic resonance imaging (MRI) scans and projected onto the PET
      images in which regional CBF values and the water perfusable tissue fraction for
      the cortical gray matter tissue (hence the volume of gray matter) were estimated.
      After the PET study, the animals were killed and stereologic analysis was
      performed to assess the gray matter mass in the corresponding ROIs.
      Reproducibility of the estimated parameters and sensitivity to various error
      sources were also evaluated. All models tested in the current study yielded PVE
      corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models
      with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a
      term for a mixture of gray matter and white matter tissues). These values were
      greater than those obtained from ROIs tracing the gray matter cortex using
      conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)).
      Among the four models, configurations that included two parallel tissue
      compartments demonstrated better results with regards to the agreement of tissue
      time-activity curve and the Akaike's Information Criteria. Error sensitivity
      analysis suggested the model that fits three parameters of the gray matter CBF,
      the gray matter fraction, and the white matter fraction with fixed white matter
      CBF as the most reliable and suitable for estimating the gray matter CBF.
      Reproducibility with this model was 11% for estimating the gray matter CBF. The
      volume of gray matter tissue can also be estimated using this model and was
      significantly correlated with the results from the stereologic analysis. However,
      values were significantly smaller compared with those measured by stereologic
      analysis by 40%, which can not be explained by the methodologic errors. In
      conclusion, the partial volume correction was essential in quantitation of
      regional CBF. The method presented in this article provided the PVE-corrected
      regional CBF in the cortical gray matter tissue. This study also suggests that
      further studies are required before using MRI derived anatomic information for
      PVE correction in PET.

PMID- 10950387
TI  - Polyanions--a lost chance in the fight against HIV and other virus diseases?
AB  - Polyanions are known to exhibit potent antiviral activity in vitro, and may
      represent future therapeutic agents. This review summarizes literature reports,
      pertinent to anionic polymers as antiviral agents. The in vitro antiviral effects
      of numerous polyanionic compounds (sulphated polysaccharides, negatively charged
      serum albumin and milk proteins, synthetic sulphated polymers, polymerized
      anionic surfactants and polyphosphates) are described. This class of antiviral
      agent exhibits several unique properties that are not shared by other presently
      known antiviral agents: (i) a remarkable broad-spectrum antiviral activity
      against HIV-1, HIV-2 and a series of other enveloped viruses; (ii) the ability to
      inhibit syncytium formation between HIV-infected and normal CD4 T lymphocytes, a
      mechanism that drastically enhances HIV infectivity; and (iii) a low induction of
      viral drug-resistance. There is increasing evidence that polyanions interfere
      with the fusion process, a vital step in the viral replication cycle. The
      inhibition of virus-cell fusion appears to be the source of the antiviral
      activity of polyanions. In vivo, the pharmacological properties of polyanions
      result in a low bioavailability of the drugs to their viral targets, and hence a
      poor antiviral activity in vivo. It is suggested that polyanions must be used in
      combination with drug delivery systems in order to become therapeutically useful
      antiviral agents. Some drug delivery systems are briefly discussed.

PMID- 10950388
TI  - Antiviral therapy for enteroviruses and rhinoviruses.
AB  - The picornaviruses are a diverse group of viral pathogens that together comprise
      the most common causes of infection of humans in the developed world. Within the
      picornavirus family are three well-known groups of human pathogens--the
      rhinoviruses, the enteroviruses (including polioviruses, coxsackieviruses and
      echoviruses) and the hepatoviruses (including hepatitis A virus). This article
      will focus on the rhinoviruses and enteroviruses, agents for which substantial
      effort has been expended, and recent successes reported, toward the development
      of safe and effective antiviral therapy.

PMID- 10950389
TI  - The bystander effect mediated by the new murine gammaherpesvirus 72--thymidine
      kinase/5'-fluoro-2'-deoxyuridine (MHV72-TK/5-FUdR) system in vitro.
AB  - To investigate the potential of murine gamma-herpesvirus 72 thymidine kinase (MHV
      72-TK) to act as a suicide gene, we used a mammalian expression vector on rat
      fibroblastoid cells deficient in the cellular TK gene. Substrate specificity was
      assessed in vitro in cells with stable expression of MHV-72-TK. The Herpes
      simplex virus 1-TK (HSV-1-TK) was used as a reference suicide gene. Unlike HSV-1
      TK modified cells, which were sensitive to ganciclovir (GCV) (IC50=9.7 microM),
      cells modified by MHV-72-TK did not show sensitivity to this drug. The use of 3'
      azido-3'-deoxythymidine (AZT) and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) did
      not affect the growth of cells expressing either MHV-72-TK or HSV-1-TK in the
      range of concentration used for AZT (0-375 microM) and for BVDU (0-50 microM). In
      contrast, 5'-fluoro-2'-deoxyuridine (5-FUdR) was extremely cytotoxic and
      effectively killed MHV-72-TK expressing cells (IC50 value 2.1 microM). This value
      was 16 times lower than that required to kill cells expressing HSV1-TK. To test
      whether the bystander effect between two heterologous cell types could be
      mediated by the MHV-72-TK/5-FUdR system in vitro, cells expressing MHV-72-TK were
      co-cultured with the tumour fibroblastoid cell line NAD for 48 hours before the
      drug (10.8 microM) was added. The cell mixtures contained various ratios of cells
      expressing MHV-72-TK (0 to 50% of total cells). Only 1% of MHV-72-TK-expressing
      cells were needed to enhance mouse tumour cell killing and to decrease the
      survival rate to 25.6%. The bystander effect was more pronounced when 10% of
      cells expressing MHV-72-TK were used, decreasing survival to 17.4%. In parallel,
      the same concentration of 5-FUdR dose only marginally inhibited tumour cell
      growth in the absence of exogenous TK activity (84% survival). These results
      demonstrate the efficiency of MHV-72-TK as a suicide gene when 5-FUdR is used as
      a prodrug. When sequenced, MHV-72-TK proved to be identical to MHV-68 strain TK.

PMID- 10950390
TI  - Novel mouse models for the investigation of experimental drugs with activity
      against human varicella-zoster virus.
AB  - Suitable small animal models for the testing of antiviral agents with activity
      against human varicella-zoster virus (VZV) have so far been lacking. Mice and
      other animals have been found to not be susceptible to VZV infection. The model
      of choice for drug development has been the infection of monkeys using simian
      varicella virus (SVV). However, while primates offer potential as models of human
      varicella disease, their use is limited as experimental models in antiviral
      research. We have developed two simple mouse models that support replication of
      human VZV in vivo. In the first, SCID mice were transplanted with human umbilical
      cord (umbilical cord cushion model) and subsequently infected with VZV. After
      infection, we were able to demonstrate increasing titres of viral DNA over a 9
      day period. In the second model, biocompatible hollow fibres were used for
      encapsulation of VZV-infected cells. The hollow fibres were then transplanted
      into immunodeficient and immunocompetent mice and infectious virions were re
      isolated. In addition, we demonstrated that both the umbilical cord cushion and
      the hollow fibre models are suitable tools to test antiviral compounds.
      Administration of BVDU ibrivudine, Helpin, (E)-5-(2-bromovinyl)-2'-deoxyuridine]
      significantly reduced the VZV titres in both models.

PMID- 10950391
TI  - Drug resistance and drug combination features of the human immunodeficiency virus
      inhibitor, BCH-10652 [(+/-)-2'-deoxy-3'-oxa-4'-thiocytidine, dOTC].
AB  - The heterosubstituted nucleoside analogue dOTC [( )-2'-deoxy-3'-oxa-4'
      thiocytidine, BCH-10652] is a racemic compound structurally related to 3TC
      (lamivudine), but has the oxygen and sulphur in the furanosyl ring transposed.
      Both the enantiomers (-)dOTC (BCH-10618) and (+)dOTC (BCH-10619) had equivalent
      activity against wild-type strains of HIV-1 in C8166 T-cells (EC50 1.0-10.0
      microM) and in PBMCs (EC50 0.1-3.0 microM). Investigation of the activity of dOTC
      and its enantiomers against laboratory strains of HIV-1 with defined resistance
      to 3TC, AZT (zidovudine), ddl (didanosine), PMEA (adefovir), nevirapine and
      saquinavir indicated that sensitivity was maintained (<3-fold change in EC50) in
      all cases, with the exception of HIV-1RF 3TC-resistant viruses. The degree of
      resistance recorded for dOTC (four- to sevenfold), (-)dOTC (five- to eightfold)
      and (+)dOTC (five- to >18-fold) against these M1841 or M184V mutants, was
      significantly less than that recorded for 3TC (>100-fold). In addition, the
      inhibitory effect of the compounds against clinical isolates of HIV-1 recovered
      from patients with suspected resistance to 3TC and AZT was investigated. Clinical
      isolates were genotyped using the Murex Line Probe Assay (LiPA) and subgrouped
      into wild-type, 3TC-resistant and dual 3TC/AZT-resistant, as well as undefined or
      mixed genotype populations. Compared with the mean EC50 values obtained with
      genotypically and phenotypically wild-type clinical isolates, the mean EC50
      values calculated for isolates phenotypically resistant to 3TC or 3TC and AZT
      were only 2.6-, 1.6- and 8.2-fold higher for dOTC, (-)dOTC and (+)dOTC,
      respectively. When the rate of emergence of virus resistant to dOTC and its
      enantiomers in vitro was investigated, virus resistant to (+)dOTC was readily
      selected for (<10 passages), and a methionine (ATG) to isoleucine (ATA) amino
      acid change at codon 184 was identified. In contrast, virus resistant to dOTC and
      (-)dOTC took longer to appear (15-20 passages), with a methionine (ATG) to valine
      (GTG) amino acid change at position 184 identified in both cases. In addition,
      virus passaged 20 times in the presence of dOTC also had a partial lysine (AAA)
      to arginine (AGA) exchange at position 65. These viruses showed only low-level
      resistance to dOTC and its enantiomers, but were highly resistant to 3TC. The
      antiviral effects of dOTC in combination with the nucleoside RT inhibitors AZT,
      3TC, d4T (stavudine) and ddl, the non-nucleoside RT inhibitor nevirapine and the
      protease inhibitors saquinavir, ritonavir and indinavir was investigated. Two-way
      drug combination assays were carried out in peripheral blood mononuclear cell
      (PBMC) cultures by measuring the reduction in p24 viral antigen levels, and data
      was analysed using the MacSynergy II program. dOTC in combination with 3TC or d4T
      showed a moderate synergistic effect while all other combinations had an additive
      interaction.

PMID- 10950392
TI  - Treatment of cowpox virus respiratory infections in mice with ribavirin as a
      single agent or followed sequentially by cidofovir.
AB  - To better understand the potential of ribavirin in the treatment of orthopoxvirus
      infections (such as those acquired through bioterrorist activities), the efficacy
      of the drug was studied in a cowpox respiratory infection model in mice under
      varying disease severity. Mice did not survive a high intranasal cowpox virus
      challenge [3 x 10(6) plaque forming units (pfu)/animal] treated with subcutaneous
      ribavirin (100 mg/kg/day for 5 days), but lived 3.9 days longer than placebos. In
      contrast, 100% of animals receiving the same dose of drug survived a 3 x 10(5)
      pfu challenge compared with 0% survival of those that received placebo. Survival
      rates of 50 and 30% occurred with ribavirin doses of 50 and 25 mg/kg/day,
      respectively. At the 100 mg/kg/day dose, ribavirin reduced lung virus titres 40
      fold on day 6 of the infection relative to titres in the placebo group. Weight
      loss resulting from illness and mean lung weights of mice treated with ribavirin
      were also significantly reduced. Mice were infected intranasally with the high 3
      x 10(6) pfu virus challenge dose and treated with 100 mg/kg/day ribavirin for 5
      days, followed by single injections of 75 mg/kg cidofovir on day 6, 7, 8 or 9.
      Cidofovir alone (without ribavirin) administered on day 6 had no beneficial
      effect on disease outcome. Ribavirin alone increased the mean time to death by
      3.7 days. Ribavirin treatment for 5 days followed by cidofovir treatment on days
      6 and 7 significantly increased the mean time to death beyond that achieved with
      ribavirin alone by 8.2 and 4.4 days, respectively, with 30 and 40% of mice
      surviving the infection. These results suggest that many individuals infected
      with an orthopoxvirus by aerosol route would benefit by a course of ribavirin
      therapy. Later, the fewer number of very sick individuals could be treated with
      intravenous cidofovir.

PMID- 10950393
TI  - Plasma renin activity in the emergency department and its independent association
      with acute myocardial infarction.
AB  - Elevated plasma renin activity (PRA) is associated with increased risk of future
      myocardial infarction (MI) in ambulatory hypertensive patients. The present study
      evaluated the relationship of PRA to the diagnosis of acute MI in patients
      presenting to an emergency department with suspected acute MI. PRA was measured
      upon entry to the emergency department, before any acute treatment, as part of
      the standard evaluation of 349 consecutive patients who were hospitalized for
      suspected MI. Diagnosis of acute MI was confirmed in 73 patients, and ruled out
      in 276. They did not differ in age (65.9 +/- 2 v 66.1 +/- 1 years), systolic (143
      +/- 4 v 140 +/- 2 mm Hg), or diastolic (81 +/- 2 v 81 +/- 1 mm Hg) pressures.
      Median PRA was 2.7-fold higher in acute MI (0.89 v 0.33 ng/L/s; P < .001). In a
      multivariate analysis controlling for other cardiac risk factors and prior drug
      therapy, PRA as a continuous variable was the predominant independent factor
      associated with acute MI (P < .0001), followed by white race (P = .002) and
      history of hypertension (P = .047). The height of the PRA level upon entry to the
      emergency department was directly and independently associated with the diagnosis
      of acute MI. These new findings extend earlier reports because they encompass
      acute MI patients, include both hypertensive and normotensive patients, and
      control for potentially confounding variables. Based on these observations, a
      randomized clinical trial is warranted to determine whether measurement of PRA in
      acute MI could refine the process by which treatments are applied.

PMID- 10950394
TI  - Association between salt sensitivity and target organ damage in essential
      hypertension.
AB  - Cardiovascular events occur more frequently in sodium-sensitive patients with
      essential hypertension; recently, sodium sensitivity was shown to be a
      cardiovascular risk factor independently of other classic factors such as blood
      pressure and cigarette smoking This study examined the relationship between salt
      sensitivity status and target organ damage in hypertensive patients. Ninety-six
      patients (35 men, 61 women) with moderate essential hypertension were studied for
      salt sensitivity status and the presence of target organ damage, including
      hypertensive retinopathy, serum creatinine, creatinine clearance, and urinary
      albumin excretion (UAE). Four different patterns of left ventricular anatomic
      adaptation were identified by categorizing patients according to the values of
      left ventricular mass index and relative wall thickness by the means of
      echocardiography. Forty-five (47%) patients were shown to be salt-sensitive, in
      contrast to 51 (53%) salt-resistant subjects. Serum creatinine and UAE were
      significantly higher in the group of salt-sensitive hypertensives (P < .05 and P
      < .001, respectively). Left ventricular mass index (LVMI), relative wall
      thickness (RWT), and left atrial index (LAI) were all significantly higher in the
      group of salt-sensitive hypertensive patients. Concentric hypertrophy was
      significantly more prevalent in the salt-sensitive group (37.8% v 11.8%; P <
      .01). The prevalence of hypertensive retinopathy in the salt-sensitive group was
      84.4%, in contrast to 59.6% in the salt-resistant group (P < .01). Multivariate
      regression analysis revealed salt sensitivity as a significant predictor of LVMI,
      RWT, and UAE, independently of age, body mass index, and mean blood pressure. In
      conclusion, salt-sensitive hypertensive patients are more prone to develop severe
      hypertensive target organ damage that may enhance their risk of renal and
      cardiovascular morbidity.

PMID- 10950395
TI  - Sodium-sensitive hypertension is not associated with higher sympathetic nervous
      system activity in older hypertensive humans.
AB  - The majority of older hypertensive humans are sodium sensitive and they are
      characterized by increased alpha-adrenergic responsiveness relative to their
      level of sympathetic nervous system (SNS) activity. To test the hypothesis that
      heightened SNS activity and/or increased alpha-adrenergic receptor responsiveness
      during sodium loading may play a role in the sodium-dependent increase in blood
      pressure in older sodium-sensitive hypertensives, we used compartmental analysis
      of [3H]norepinephrine (NE) kinetics to determine the release rate of NE into an
      extravascular compartment (NE2) as an index of systemic SNS activity and
      determined forearm blood flow responses to graded intrabrachial artery NE and
      angiotensin II (ANG II) infusions and platelet membrane alpha2-receptor
      properties in 24 older (age 64 +/- 7 years) hypertensive subjects. Subjects were
      studied at the end of 1 week of a low (20 mmol/day)- and again at the end of 1
      week of a high (200 mmol/day)-sodium diet. Subjects were categorized as sodium
      sensitive (SS) if they had a > or = 5 mm Hg increase in mean arterial blood
      pressure (MABP) with dietary sodium loading (n = 16), or sodium-resistant (SR) if
      their MABP increased by < 5 mm Hg (n = 8). Neither dietary sodium intake nor
      sodium-sensitivity status significantly affected arterial plasma NE levels, NE2,
      or other NE kinetic parameters. Forearm blood flow responses to NE or to ANG II,
      and platelet alpha2-receptor properties were similar between the SS and SR
      groups. These results suggest that the sodium-dependent increase in MABP that
      characterizes SS hypertension among older humans is not because of an increase in
      systemic SNS activity or increased arterial adrenergic receptor responsiveness.

PMID- 10950396
TI  - Ethnic differences in nocturnal blood pressure decline in treated hypertensives.
AB  - Lack of a nocturnal decline in blood pressure (BP) has been associated with more
      severe end organ damage in hypertensives, and blacks appear less likely than
      whites to have a > 10% drop in nighttime BP ("dipping"). Little information is
      available about the relationship between treatment regimens, ethnic group
      classification, and dipping in treated hypertensive patient populations. We
      obtained 24-h ambulatory BP readings in 438 adult white (n = 103), black (n =
      200) and Hispanic (n = 135) treated hypertensives. Tycos monitors were connected
      in patients' homes before their usual morning medication dose time. Research
      assistants administered a quality-of-life questionnaire, recorded patients' drug
      regimen, and observed the patients take their morning dose. Monitors were
      programmed to record BP every 30 min. Dippers were defined as persons who had a
      drop of > or = 10% decline in average daytime (08:00 to 22:00) compared to
      nighttime (00:00 to 04:00) BP. Logistic regression modeling was used to assess
      the relationship between demographic and treatment variables and probability of
      dipping. Twenty-four-hour average BP was similar in all three ethnic groups.
      However, the absence of a systolic dip was significantly more common in black and
      Hispanic men than in white men (OR black v white = 11.54, 95% CI = 3.92 to 34.01;
      OR Hispanic v white = 7.32, 95% CI = 2.47 to 21.68). There were no ethnic group
      differences in probability of systolic dipping among women. Absence of a
      diastolic dip was approximately twice as common in blacks and Hispanics than in
      whites, with no marked gender-by-ethnic-group interaction in the magnitude of the
      association. Of the 10 most commonly prescribed antihypertensives, no single drug
      was positively associated with nocturnal BP decline. Later versus earlier morning
      dose time, but not once-a-day dosing, was associated with absence of dipping.
      Treated black and Hispanic hypertensives are less likely to "dip" than non
      Hispanic whites. No particular drug was positively associated with dipping.

PMID- 10950397
TI  - Low wall shear stress in carotid arteries in subjects with left ventricular
      hypertrophy.
AB  - Left ventricular hypertrophy (LVH) is an independent risk factor for
      cardiovascular complications including atherosclerosis. The close linkage between
      LVH and carotid atherosclerosis has been the focus of much research. However, the
      underlying mechanism linking the two conditions is not fully understood. Low wall
      shear stress contributes to intimal thickening and atherosclerosis development as
      a local mechanism. In the present study, we investigated the relationship between
      wall shear stress and LVH in subjects with risk factors for atherosclerosis.
      Eighty subjects with at least one risk factor for atherosclerosis; ie,
      hypertension, diabetes mellitus, hyperlipidemia, or smoking, were enrolled.
      Intimal-medial thickness (IMT), number of plaques, internal dimensions, and blood
      flow velocity in the common carotid artery were evaluated. Wall shear stress was
      calculated using a Poiseuillean parabolic model of velocity distribution: shear
      stress = 4 x blood viscosity x central flow velocity/internal dimension. Subjects
      were divided into two groups; LVH(-) (n = 36) and LVH(+) (n = 44), according to
      their left ventricular mass index (LVMI). Mean shear stress and systolic peak
      shear stress were significantly lower in subjects with LVH compared with subjects
      without LVH. Furthermore, mean shear stress (r = -0.42, P < .0001) and peak shear
      stress (r = -0.31, P < 0.01) were significantly inversely related to LVMI.
      Stepwise regression analysis revealed that wall shear stress independently
      correlated with LVMI as well as IMT. These results indicate that low shear stress
      could function as a local factor in the development of atherosclerosis in
      subjects with LVH.

PMID- 10950399
TI  - Relationship between birth weight and cardiovascular risk factors in Japanese
      young adults.
AB  - A number of studies have recently shown a significant inverse relationship
      between birth weight and incidences of chronic and metabolic disorders such as
      hypertension and type 2 diabetes, though the findings are not consistent. So far,
      few investigations have been performed to determine whether this relationship
      exists in Japanese young adults. We investigated the influence of birth weight on
      cardiovascular risk factors such as blood pressure and several metabolic
      variables in Japanese young adults. The data of 299 medical students of Dokkyo
      University School of Medicine (207 men, 92 women; mean age +/- SD: 23 +/- 2
      years) who underwent a medical check-up in 1998 were analyzed. Information on
      pregnancies and measurements at birth were obtained from The Maternal and Child
      Health Handbook, which is provided to every pregnant woman by the Ministry of
      Health and Welfare of Japan. Blood pressure was measured twice in the sitting
      position using an automated device based on the cuff-oscillometric method. The
      systolic and diastolic blood pressure in young adulthood was positively
      correlated with current body weight and body mass index (BMI) in both genders.
      Although birth weight was not significantly correlated with blood pressure in the
      young adults examined in the present study, male birth weight was inversely
      correlated with serum total cholesterol and triglyceride concentrations in young
      adulthood, independently of current BMI. These results partly support the
      hypothesis for the first time that low birth weight may be one of the risk
      factors for subsequent cardiovascular disease in Japanese men.

PMID- 10950398
TI  - Lowering of blood pressure and predictors of response in patients with left
      ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint.
AB  - The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is
      a double-blind, prospective, parallel-group study comparing the effects of
      losartan with those of atenolol on the reduction of cardiovascular complications
      in patients (n = 9,194) with essential hypertension and with
      electrocardiographically (ECG) documented left ventricular hypertrophy (LVH).
      Baseline blood pressure was 174.4/97.8 mm Hg (mean), age 66.9 years, body mass
      index 28.0 kg/m2; 54.1% were women and 12.5% had diabetes mellitus. This
      population will be treated until at least 1,040 have a primary endpoint. After
      five scheduled visits and 12 months of follow-up, blood pressure decreased by
      23.9/12.8 mm Hg to 150.5/85.1 mm Hg (target < 140/90 mm Hg). The mandatory
      titration level of < or = 160/95 mm Hg was reached by 72.1% of the patients. At
      the 12-month visit, 22.7% of all patients were taking blinded study drug alone,
      44.3% were taking blinded drug plus hydrochlorothiazide (HCTZ), and 17.7% were
      taking blinded drugs plus HCTZ and additional drugs. Controlling for all other
      variables, patients in the US received more medication and had 2.4 times the odds
      of achieving blood pressure control than patients in the rest of the study (P <
      .001). Previously untreated patients (n = 2,530) had a larger initial decrease in
      blood pressure compared with those previously treated. Diabetics (n = 1,148)
      needed more medication than nondiabetics to gain blood pressure control. Only
      13.9% of the patients had discontinued blinded study drug and 1.4% missed the
      revisit at 12 months. These data demonstrate both the successful lowering of
      blood pressure during 12 months of follow-up in a large cohort of patients with
      hypertension and LVH on ECG, but also emphasize the need for two or more drugs to
      control high blood pressure in most of these patients. Being previously treated
      and having diabetes were associated with less blood pressure response, whereas
      living in the US indicated better blood pressure control. It has been possible to
      keep most of these patients with complicated hypertension taking blinded study
      drug for 12 months.

PMID- 10950400
TI  - Gender-dependent differences in plasma leptin in essential hypertension.
AB  - Leptin, the gene product of the ob gene, is influenced by gender and insulin
      sensitivity. Because in human hypertension there are important endocrine
      hemodynamic gender-dependent differences, we compared plasma leptin in 39
      essential hypertensives (EH) and in 27 normotensive healthy subjects (HS) matched
      for gender, age, and fat mass. Fat mass was measured by bioelectrical impedance
      analysis (BIA), plasma leptin by a sensitive radioimmunoassay RIA (intraassay CV
      < 6%), and insulin sensitivity by the HOMA-R index. Both in essential
      hypertensives and in normotensive subjects plasma leptin was consistently higher
      in females than in males and was strictly related to fat mass. Gender differences
      in plasma leptin were not explained by differences in fat mass. Separate analysis
      of data by gender showed that leptin was significantly higher (P < .05) in
      hypertensive men (median, 5.4 ng/mL; interquartile range, 4.1-9.5) than in
      normotensive men (4.6 ng/mL, 2.6-7.4) whereas it was identical in hypertensive
      and normotensive women. In essential hypertensives, in a multiple regression
      model only fat mass, gender, and the HOMA-R index were independently linked to
      plasma leptin. Similarly, fat mass and gender were independent predictors of
      plasma leptin in normotensive subjects. In the combined group of hypertensive and
      normotensive men, heart rate as well as systolic and diastolic pressure were
      univariate predictors of leptin. However, in a multivariable model only heart
      rate was independently related to leptin, and neither systolic nor diastolic
      pressure contributed significantly to explain the variability in plasma leptin.
      No relationship was found between leptin and heart rate or systolic or diastolic
      pressure in women. These results support the notion that leptin may participate
      in the gender-dependent variability of human hypertension.

PMID- 10950401
TI  - Clinically additive effect between doxazosin and amlodipine in the treatment of
      essential hypertension.
AB  - The Joint National Committee on Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure has reported that combinations of low doses of
      antihypertensive agents from different classes may provide additional
      antihypertensive efficacy and minimize the likelihood of dose-dependent adverse
      effects. Doxazosin and amlodipine, alone and in combination, were compared for
      efficacy in reducing blood pressure (BP) in 75 patients with predominantly
      moderate (Stage 2) hypertension. This was a double-blind, randomized, crossover
      study. After a 2-week washout period, patients in group A (n = 37) received
      amlodipine 10 mg and patients in group B (n = 38) received doxazosin 4 mg for 6
      weeks. All patients then received reduced-dose combination therapy (amlodipine 5
      mg and doxazosin 2 mg) for 6 weeks. Subsequently, patients received 6 weeks of
      monotherapy with the alternate medication (group A received doxazosin 4 mg and
      group B received amlodipine 10 mg). During both monotherapy periods, doxazosin
      and amlodipine significantly reduced systolic and diastolic BP (P < .001 v
      baseline). BP further decreased with combination therapy (P < .01 v monotherapy).
      The percentage of patients with Stage 2 hypertension who achieved a target BP of
      < 140/< 90 mm Hg increased from 78% with monotherapy to 94% with combination
      therapy. Fewer adverse effects were observed during combination therapy. It is
      concluded that there is an additional fall in blood pressure when reduced doses
      of doxazosin and amlodipine are used in combination for the treatment of
      hypertension, suggesting that doxazosin should be considered as an effective add
      on treatment to calcium-channel blockers.

PMID- 10950402
TI  - 11Beta-hydroxysteroid dehydrogenase activity in spontaneously hypertensive and
      Dahl rats.
AB  - The role of the enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD) in
      hypertension remains unknown even if it appears that the inappropriately
      decreased 11betaHSD activity might be involved in a process that leads to high
      blood pressure. The possible changes of 11betaHSD were therefore investigated in
      rats with spontaneous or salt-induced hypertension. The adult male rats of the
      following genotypes were used: spontaneously hypertensive rats (SHR),
      normotensive Wistar-Kyoto rats (WKY), Dahl salt-sensitive rats fed either a high
      salt diet containing 8% NaCl (DS-HS) or low-salt diet containing 0.2% NaCl (DS
      LS), and Dahl salt-resistant rats fed the same diets (DR-HS, DR-LS). 11betaHSD
      was investigated in colon, aorta, renal cortex, and renal medulla and was
      assessed as percentage conversion of [3H]corticosterone to [3H]11
      dehydrocorticosterone in the presence of NAD or NADP. The results demonstrated
      that genotype exerts a significant effect on 11betaHSD. 11betaHSD activity was
      significantly increased in colon and renal medulla of SHR compared with WKY rats.
      No significant differences were observed in renal cortex and aorta. In Dahl rats
      kept on a low-salt diet, 11betaHSD activity was significantly higher in colon,
      renal medulla, and cortex of DS-LS than in DR-LS rats but no difference was
      observed in aorta. The differences disappeared in age-matched DS and DR rats fed
      the high-salt diet. Increased dietary sodium intake stimulated the activity of
      11betaHSD in renal cortex and medulla of DR rats and decreased the activity in
      colon of DS rats. We conclude that the development of spontaneous and salt
      induced hypertension is not associated with decreased activity of 11betaHSD.
      However, the results showed that salt intake is able to modulate the activity of
      11betaHSD and that 11betaHSD in DS and DR rats responds to high dietary salt
      intake in a different manner.

PMID- 10950403
TI  - Do patients with de novo hypertension differ from patients with previously known
      hypertension when malignant phase hypertension occurs?
AB  - Malignant phase hypertension (MHT) represents the most severe form of
      hypertension, and many consider that this condition only occurs in poorly managed
      patients with previously known hypertension. To investigate this further, we
      studied 350 patients with MHT on the West Birmingham MHT database: 195 (55.7%) of
      these presented de novo, without any known past history of hypertension (Group
      1), and 146 (41.7%) were previously known hypertensives (Group 2), of whom 86
      were receiving antihypertensive therapy; in 9 patients, the status was uncertain.
      Median duration of clinical followup was similar in both groups (36.0 v 37.5
      months, Mann-Whitney test P = .795). Patients presenting de novo with MHT (Group
      1) were younger, with a predominance of whites and men. Nevertheless, the
      clinical features, blood pressures, and renal function at presentation were
      similar to MHT patients with previously known hypertension. Renal function at
      follow-up was also similar in both groups. There was an excess of women and
      nonwhites in MHT patients with previously known hypertension (Group 2), who also
      had higher mean follow-up blood pressures. On univariate life-table analysis,
      there was no statistically significant difference in survival time between Groups
      1 and 2 (mean 57.5 v 63.5 months, median 36.0 v 37.0 months; log-rank test, P =
      .456). Using a multivariate Cox analysis of baseline variables, the independent
      predictors of outcome (death or dialysis) were age at presentation (P = .0019),
      diastolic blood pressure (P = .0466), serum urea (P = .006), and serum creatinine
      (P < .001). Whether the patient had presented de novo, without any known history
      of hypertension (Group 1) or had previously known hypertension (Group 2) did not
      independently predict outcome (P = .6549). We suggest that MHT can occur de novo
      in patients without previously known hypertension, and the clinical
      characteristics and prognosis in such patients were similar to MHT patients with
      previously known hypertension.

PMID- 10950404
TI  - Normal values of blood pressure self-measurement in view of the 1999 World Health
      Organization-International Society of Hypertension guidelines.
AB  - New guidelines for the management of hypertension have been published in 1999 by
      the World Health Organization (WHO) and the International Society of Hypertension
      (ISH). The WHO/ISH Committee has adopted in principle the definition and
      classification of hypertension provided by the JNC VI (1997). The new
      classification defines a blood pressure of 120/80 mm Hg as optimal and of 130/85
      mm Hg as the limit between normal and high-normal blood pressure. It is unclear
      which self-measured home blood pressure values correspond to these office blood
      pressure limits. In this study we reevaluated data from our Dubendorf study to
      determine self-measured blood pressure values corresponding to optimal and normal
      office blood pressure using the percentiles of the (office and home) blood
      pressure distributions of 503 individuals (age, 20 to 90 years; mean age, 46.5
      years; 265 men, 238 women). Self-measured blood pressure values corresponding to
      office values of 130/85 mm Hg and 120/80 mm Hg were 124.1/79.9 mm Hg and
      114.3/75.1 mm Hg. Thus, we propose 125/80 mm Hg as a home blood pressure
      corresponding to an office blood pressure of 130/85 mm Hg (WHO 1999: normal) and
      115/75 mm Hg corresponding to 120/80 mm Hg (optimal).

PMID- 10950405
TI  - Lack of association between human TGF-beta1 gene variants and primary
      hypertension.

PMID- 10950406
TI  - Blood pressure self-measurement: where do we go from here?

PMID- 10950407
TI  - Laser treatments with verteporfin therapy and its potential impact on retinal
      practices.
AB  - BACKGROUND: In the 1990s, the only available treatment for neovascular age
      related macular degeneration (ARMD) was laser photocoagulation, but a minority of
      patients could be treated. Photodynamic therapy with verteporfin potentially
      allows many more patients to be treated. The authors' aim was to assess the
      impact of this increase on retinal practices. METHODS: The number of patients who
      received laser photocoagulation in 1998 was determined. Based on that number and
      a retrospective review of 1000 consecutive records of new patients with ARMD
      referred to the Associated Retinal Consultants practices during 1998, estimates
      were made of how many patients would have been eligible for verteporfin therapy.
      RESULTS: Of the 1000 patients, 171 had predominantly classic subfoveal choroidal
      neovascularization secondary to ARMD and would have been eligible for verteporfin
      therapy, compared with 99 treated with laser photocoagulation according to
      Macular Photocoagulation Study guidelines. If this patient population is
      representative of the general population, approximately 84,000 patients would be
      eligible for verteporfin therapy in the United States per year, compared with
      42,000 for laser photocoagulation. This would lead to 286,000 verteporfin
      treatments per year if retreatments are required. CONCLUSIONS: This increase in
      treatments for neovascular ARMD will have a considerable impact on retinal
      practices. Although the resources that will need to be expended are high, the
      potential benefit of verteporfin therapy in reducing vision loss will outweigh
      the costs.

PMID- 10950408
TI  - Incremental cost-effectiveness of laser therapy for choroidal neovascularization
      associated with histoplasmosis.
AB  - PURPOSE: Laser photocoagulation has been shown in a large clinical trial to be
      efficacious in reducing the degree of vision loss occurring secondary to
      choroidal neovascularization (CNV) associated with ocular histoplasmosis.
      Nevertheless, data are lacking concerning the impact of the therapy on quality of
      life and its value to stakeholders in health care. Recently, information
      concerning the utility value of visual states has become available. Accordingly,
      the authors undertook to ascertain the cost-effectiveness of laser
      photocoagulation for the treatment of extrafoveal CNV occurring in eyes with
      ocular histoplasmosis. METHODS: Design--A computer simulation, econometric model
      is presented to evaluate the incremental cost-effectiveness of laser
      photocoagulation therapy, as compared with the natural course of the disease, for
      the treatment of patients with extrafoveal CNV associated with ocular
      histoplasmosis. The model applies long-term visual data from previous clinical
      trials, utility analysis (which reflects patient perceptions of quality of life),
      decision analysis with Markov modeling, and present value analysis with
      discounting to account for the time value of money. Outcome measure--Cost per
      quality-adjusted life-year gained from treatment. RESULTS: Laser photocoagulation
      therapy for extrafoveal CNV associated with ocular histoplasmosis costs $4167
      1999 US dollars (at a 3% discount rate) for each quality-adjusted life-year
      gained from treatment. Sensitivity analysis shows that changing the discount rate
      substantially alters the cost-effectiveness, with a value of $1339 at a 0%
      discount rate and $56,250 at a 10% discount rate. CONCLUSIONS: Compared with
      therapeutic modalities for other disease entities, laser therapy for the
      treatment of extrafoveal CNV associated with ocular histoplasmosis appears to be
      a cost-effective treatment from the patient preference-based point of view.

PMID- 10950409
TI  - Rhegmatogenous retinal detachment after laser-assisted in situ keratomileusis
      (LASIK) for the correction of myopia.
AB  - PURPOSE: To report a case series of rhegmatogenous retinal detachment (RRD) after
      laser-assisted in situ keratomileusis (LASIK) and its incidence at a mean of 24
      months. METHODS: The clinical charts of patients who experienced RRD after LASIK
      were reviewed. Five refractive surgeons and 24,890 myopic eyes that underwent
      surgical correction of myopia ranging from -0.75 to -29.00 diopters (D) (mean, 
      6.19 D) participated in this study. RESULTS: Thirteen eyes from 12 patients
      developed RRD after LASIK. Rhegmatogenous RD occurred between 1 and 36 months
      (mean, 12.6 months) after LASIK. Eyes that developed RRD had from -1.50 to -16.00
      D of myopia (mean, -6.96 D) before LASIK. Rhegmatogenous RD were managed with
      vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or
      pneumatic retinopexy techniques. The incidence of RRD at a mean of 24 months
      after LASIK in this study was 0.05%. CONCLUSIONS: Rhegmatogenous RD after LASIK
      is infrequent. If managed promptly, good vision can result. No cause-effect
      relationship between LASIK and RD can be proved from this study, but the authors
      recommend that patients scheduled for refractive surgery undergo a thorough
      dilated indirect fundus examination with scleral depression and treatment of any
      retinal lesions predisposing them to the development of RRD before LASIK surgery
      is performed.

PMID- 10950410
TI  - Effect of laser-assisted in situ keratomileusis on the retinal nerve fiber layer.
AB  - PURPOSE: To assess the effects of laser-assisted in situ keratomileusis (LASIK)
      on the retinal nerve fiber layer (RNFL). METHOD: In a prospective study, the RNFL
      thickness of 35 eyes of 20 consecutive patients was measured before and 1 month
      after LASIK by scanning laser polarimetry. RESULTS: The postoperative integrals
      and averages of RNFL thickness were statistically significantly lower than
      preoperative values, except in the temporal quadrant. CONCLUSION: LASIK has a
      significant effect on RNFL thickness determined by scanning laser polarimetry.
      Further studies are needed to determine whether the corneal compensation
      algorithms are affected by the keratome flap, whether the decreased averages and
      integrals of the RNFL thickness are reversible, and how to protect the RNFL.

PMID- 10950411
TI  - A randomized controlled study of the use of transscleral diode laser and
      cryotherapy in the management of rhegmatogenous retinal detachment.
AB  - PURPOSE: Cryotherapy, the most common modality used to create a chorioretinal
      adhesion during retinal reattachment surgery, is associated with the dispersion
      of viable pigment epithelial cells and breakdown of the blood-ocular barrier,
      which are thought to be causative in a number of postoperative events, including
      macular pucker, proliferative vitreoretinopathy (PVR), and cystoid macular edema.
      Transscleral diode laser has been used successfully to create a chorioretinal
      adhesion in retinal reattachment surgery (diopexy) and experimentally has been
      shown to cause less pigment dispersion and blood-ocular barrier breakdown than
      cryotherapy. The authors carried out a prospective randomized study to compare
      the results and complication rates of transscleral diopexy with those of cryopexy
      during surgery for rhegmatogenous retinal detachment (RRD). METHODS: Data from
      120 patients with recent onset RRD without significant PVR who were suitable for
      scleral buckling surgery and randomized to treatment using diode laser or
      cryotherapy were analyzed. The primary outcome measure was reattachment at 6
      months with one operation. Secondary outcome measures were pain and swelling on
      the first postoperative day, cystoid macular edema as assessed angiographically
      at 6 weeks, and visual acuity, macular epiretinal membrane, and pigment migration
      under the fovea at 3 months. RESULTS: There was no significant difference between
      the primary and secondary outcome measures between the two treatment groups, with
      a primary success rate of 83% in the diode group and 92% in the cryotherapy
      group. Pain and postoperative swelling on the first postoperative day were
      equivalent. Cystoid macular edema was angiographically present in 12% in the
      diode group and 14% in the cryotherapy group. Visual acuity of at least 20/40 was
      achieved in 54% of patients in both groups. The rate of PVR was 5% in the diode
      group and 3% in the cryotherapy group. CONCLUSION: In this study of patients with
      uncomplicated RD without significant preoperative PVR, the experimentally shown
      benefits of transscleral diode laser did not result in significant improvement in
      the results of reattachment surgery compared with cryotherapy.

PMID- 10950412
TI  - Retinal detachment in Marfan syndrome.
AB  - PURPOSE: To report postsurgical findings in patients with Marfan syndrome and
      retinal detachment (RD). METHODS: The authors identified and retrospectively
      reviewed the charts of one cohort of 12 patients (15 eyes) with Marfan syndrome
      and RD who were operated on at the Wilmer Institute and a second cohort of 16
      such patients (24 eyes) who were operated several years earlier and elsewhere.
      RESULTS: First cohort--Final visual acuity (VA) was 20/80 or better and the
      retina was flat in all five phakic eyes (100%). The RD occurred after the eye had
      undergone lens removal in 10 eyes, 6 of which (60%) had a final VA of 20/80 or
      better, and 9 of which (90%) had a final VA of 5/200 or better (P = 0.20). Second
      cohort--The final VA was 20/80 or better and the retina was flat in 6 of the 7
      phakic eyes (86%). Among 17 aphakic or pseudophakic eyes, only 5 (29%) had a flat
      retina and VA of 20/80 or better, whereas 12 (71%) had no light perception (P =
      0.03). CONCLUSIONS: The results of RD operations done in the past in Marfan
      patients were worse when the eye was aphakic. In most cases operated more
      recently, the prognosis for successful RD repair was good regardless of whether
      the eye was phakic.

PMID- 10950413
TI  - External versus internal approach to the removal of metallic intraocular foreign
      bodies.
AB  - OBJECTIVE: To review the management of metallic intraocular foreign bodies (IOFB)
      at a single institution and to compare the use of internal and external
      approaches for their removal. SUBJECTS AND METHODS: A retrospective review was
      conducted on 70 eyes from 70 patients who underwent surgical removal of a
      metallic IOFB with either an internal (vitrectomy followed by forceps or internal
      magnet use) or external approach (large electromagnet) by seven vitreoretinal
      surgeons at a single institution between 1973 and 1996. Visual acuity and
      complications occurring with the two approaches were the main outcome measures
      studied. RESULTS: Overall, patients showed significant improvement in visual
      acuity following surgical intervention (P < 0.001) despite widely varying
      surgical techniques. When the authors compared patients treated with an external
      versus an internal approach they found no statistically significant difference
      with regard to visual outcome and a trend toward a higher rate of postoperative
      endophthalmitis in the external approach group. CONCLUSION: Surgical removal of
      metallic IOFB results in significant visual improvement. The external approach to
      the removal of magnetic metallic IOFB remains a viable treatment option in select
      cases.

PMID- 10950414
TI  - Phototoxicity from systemic sodium fluorescein.
AB  - PURPOSE: To confirm the occurrence of phototoxicity due to systemic fluorescein
      in a dose consistent with retinal angiographic testing and to approximate the
      prevalence of this reaction in a small group of volunteers. METHODS: Fourteen
      volunteers underwent a controlled challenge test by applying a topical sunscreen
      and exposing skin areas to direct sunlight before and after fluorescein
      administration. RESULTS: Two subjects experienced marked cutaneous blanching
      erythema, mild vesiculation, and pain in sun-exposed areas within 1 hour of
      exposure. The reaction faded over a period of days without tanning. CONCLUSIONS:
      Consistent with its in vitro properties as a photodynamic dye, fluorescein may
      rarely act as a phototoxic agent in humans at doses employed for fluorescein
      retinal angiography. It is unclear why this reaction has not been reported more
      frequently, given the large number of patients undergoing this ophthalmic
      procedure annually.

PMID- 10950415
TI  - Referral delay and ocular surgical outcome in Terson syndrome.
AB  - BACKGROUND: In Terson syndrome, vitreous hemorrhage can result from intracranial
      hypertension associated with intracranial bleeding. The vitreous hemorrhage can
      cause a considerable visual handicap. The aim of this study was to determine the
      outcome of surgery in patients with Terson syndrome and any delay in referral to
      an ophthalmologist. METHODS: Retrospective case review of 25 eyes of 17 patients
      undergoing vitrectomy for Terson syndrome. Delay in presentation to an
      ophthalmologist, intraoperative and postoperative complications, and the final
      visual acuity were noted. RESULTS: The mean interval between visual symptoms and
      referral to an ophthalmologist was 5.2 months for the nine unilateral cases and
      4.9 months for the eight bilateral cases. Intraoperative complications included
      retinal break (2) and retinal dialysis (3). Late complications included
      epiretinal membrane (4), ghost cell glaucoma (1), and cataract (8). Twenty-two of
      the 25 eyes achieved a final visual acuity of 20/30 or better. CONCLUSION:
      Vitrectomy for vitreous hemorrhage in Terson syndrome is a safe and effective
      procedure, offering a rapid and prolonged improvement in vision. There is good
      reason to consider early vitrectomy, particularly when the hemorrhage is
      bilateral and dense.

PMID- 10950416
TI  - Potassium iodate toxic retinopathy: a report of five cases.
AB  - BACKGROUND: Potassium iodate (KIO3) is an iodized salt used for iodine
      supplementation in areas endemic for goiter. KIO3 overdose in humans is rare. The
      authors report unusual cases of retinal toxicity from KIO3 overdose that caused
      acute vision loss. METHODS: The clinical manifestations, toxic dosage of iodate,
      and ocular changes in five patients who had taken a KIO3 overdose were analyzed.
      Electroretinography, visual evoked potential (VEP), and fundus fluorescein
      angiography (FA) were performed to study retinal function and changes. RESULTS:
      Two men and three women (age 22-65 years) ingested KIO3 solution at a
      concentration between 187 and 470 mg/kg body weight. Visual acuity ranged from
      light perception with projection to counting fingers and decreased from 2 to 12
      hours after ingestion. Fundus FA showed bilateral extensive areas of retinal
      pigment epithelial (RPE) window defects, and electroretinography and VEP showed
      marked impairment of retinal function. Visual acuity improved from counting
      fingers to 20/80 in 3 months. CONCLUSION: Potassium iodate can produce retinal
      toxicity that damages RPE and photoreceptor cells. The recovery of retinal
      function depends on the amount of chemical absorption, the regeneration of RPE,
      and the recovery function of photoreceptor cells.

PMID- 10950417
TI  - Posterior segment neovascularization associated with acute ophthalmic artery
      obstruction.
AB  - PURPOSE: To report previously unrecorded ocular neovascularization associated
      with acute ophthalmic artery obstruction (AOAO) that presents clinical
      manifestations of acute concomitant obstruction of the retinal and posterior
      ciliary circulations. METHODS: This report documents the clinical, fluorescein
      angiographic, and histopathologic findings in two patients with AOAO followed by
      posterior segment neovascularization. RESULTS: Ophthalmoscopic findings showed
      whitening of the posterior pole, arterial attenuation, and a pale optic disk.
      Serial fluorescein angiograms showed a nearly total shutdown of choroidal and
      retinal perfusion, degeneration of the retinal pigment epithelium and
      choriocapillaris, and eventual development of a huge neovascular frond at the
      posterior pole. Histopathologic examination of the enucleated eyeball showed
      inner retinal necrosis caused by central retinal artery obstruction, degeneration
      of the outer retina with choriocapillaris obstruction caused by impairment of
      choroidal circulation, and a thick preretinal neovascular frond at the posterior
      pole. CONCLUSIONS: These results suggest that AOAO can induce ocular
      neovascularization, which to the authors' knowledge has not yet been reported.

PMID- 10950418
TI  - Absence of herpesvirus DNA by polymerase chain reaction in ocular fluids obtained
      from immunocompetent patients.
AB  - OBJECTIVE: To assess the prevalence of herpesvirus DNA in ocular fluids obtained
      from healthy patients undergoing vitreoretinal surgery. BACKGROUND: Polymerase
      chain reaction (PCR) has been used to detect herpesvirus DNA in patients with
      acute retinal necrosis and cytomegalovirus retinitis. Little is known regarding
      the prevalence of detectable herpesvirus DNA in ocular fluids collected from
      healthy seropositive patients with no clinical evidence of viral retinitis.
      METHODS: Seventy-five intraocular specimens (35 aqueous and 40 vitreous samples)
      were collected from 75 patients undergoing scleral buckling or vitrectomy. Using
      a PCR-based assay, the authors tested each specimen for the presence of
      herpesvirus genome DNA with primers specific for cytomegalovirus, Epstein-Barr
      virus, herpes simplex virus types 1 and 2, and varicella zoster virus. Serologic
      testing for immunoglobulin G (IgG) and IgM levels corresponding to each of the
      herpesviruses was also performed. RESULTS: Of the 75 samples tested, none was
      found to harbor herpesvirus DNA. The assay did not give false-positive results in
      patients with active intraocular inflammation. The sensitivity of the assay was
      0.08 infection-forming units for cytomegalovirus, 0.6 tissue culture infectious
      doses for herpes simplex virus, 0.5 infected-cell equivalents for Epstein-Barr
      virus, and 0.03 focus-forming units for varicella zoster virus. The percentage of
      patients with positive herpesvirus serology ranged from 86% to 100% and was
      consistent with rates observed in the general population. CONCLUSIONS: The
      prevalence of herpesvirus DNA detectable by PCR techniques in ocular fluids
      appears to be quite low despite the high proportion of patients who tested
      positive for herpesvirus antibodies. Therefore, a positive result obtained in a
      patient presenting with vitreoretinal inflammation should be regarded as
      significant.

PMID- 10950419
TI  - Ocular and orbital blood flow in cigarette smokers.
AB  - OBJECTIVE: To report the effect of cigarette smoking on the blood flow velocity
      of the ophthalmic artery (OA), central retinal artery (CRA), and posterior
      ciliary artery (PCA) in patients who smoke at least 20 cigarettes a day. METHODS:
      The color duplex scanner was used to measure the systolic and diastolic flow
      velocity of the OA, CRA, and PCA in 10 smokers and 11 nonsmokers. RESULTS: Both
      the systolic and diastolic flow velocity decreased in the OA, CRA, and PCA in
      smokers compared with nonsmokers. The systolic flow decreased by as much as 36%
      and the diastolic flow by as much as 52%. This decrease was significant for the
      flow velocity of the CRA and PCA but not for the OA. An increase in the
      resistance index was also found. CONCLUSION: The authors believe that the
      decrease in the flow velocity of these vessels may be due to an increase in the
      vascular resistance of the vessels of the retina and optic nerve head in smokers.
      This may be important in patients with eye disease in whom altered blood flow
      already contributes to the ocular or orbital pathology.

PMID- 10950420
TI  - Diagnostic and therapeutic challenges. A 35-year-old woman had sudden onset of
      blurring of vision in her right eye.

PMID- 10950421
TI  - Dexamethasone sustained drug delivery implant for the treatment of severe
      uveitis.

PMID- 10950422
TI  - Three-dimensional optical coherence tomography of vitreomacular traction syndrome
      before and after vitrectomy.

PMID- 10950423
TI  - Sympathetic ophthalmia after three pars plana vitrectomies without prior ocular
      injury.

PMID- 10950424
TI  - Bilateral choroidal metastasis from adenoid cystic carcinoma of the submandibular
      gland.

PMID- 10950425
TI  - Intravitreal pigment dispersion as a complication of transpupillary thermotherapy
      of choroidal melanoma.

PMID- 10950426
TI  - Small choroidal melanoma with intraocular spread.

PMID- 10950427
TI  - Delayed onset of polymicrobial postsurgical endophthalmitis.

PMID- 10950428
TI  - Posttraumatic endophthalmitis due to CDC coryneform group A-3 bacteria.

PMID- 10950429
TI  - Interferon-associated retinopathy in a young, insulin-dependent diabetic patient.

PMID- 10950430
TI  - Submacular hemorrhage during scleral buckling surgery treated with an
      intravitreal air bubble.

PMID- 10950431
TI  - Ciliary body detachment associated with transient myopic shift after pars plana
      vitrectomy.

PMID- 10950432
TI  - APMPPE associated with Wegener's granulomatosis.

PMID- 10950433
TI  - Dense premacular hemorrhage from a retinal macroaneurysm treated by argon laser.

PMID- 10950434
TI  - Vitreous biopsy with air infusion: safety and effectiveness.

PMID- 10950435
TI  - Separation of the posterior hyaloid in eyes with macular hole using a 33-gauge
      pick.

PMID- 10950436
TI  - A new instrument for scleral buckling procedures.

PMID- 10950437
TI  - Modification of the Tano Diamond Dusted Scraper.

PMID- 10950438
TI  - Modulation of structural protein content of the myotendinous junction following
      eccentric contractions.
AB  - The objective of this study was to test the hypothesis that vinculin and talin,
      two cytoskeletal proteins of the myotendinous junction (MTJ), would be up
      regulated following damaging eccentric contractions. Mouse plantar flexor muscles
      were submitted in situ to three 5 min periods of eccentric contractions. Talin
      and vinculin content, in vitro contractile properties and MTJ histology were
      examined at 0, 3, 7, 14, and 28 days post-exercise. The eccentric protocol led to
      significant decreases in maximum tetanic tension at 0, 3, and 7 days post
      protocol. Histological examination did confirm that tissue damage was present at
      the MTJ where talin and vinculin are highly concentrated. In the type I soleus
      muscle talin content increased slightly at 7 days post-eccentric protocol
      compared to SHAM. In the type II plantaris muscle eccentric contraction led to an
      increase for vinculin and talin contents that was 2-3 fold higher than in the
      soleus; these significant changes were still present 28 days postexercise. These
      results show that eccentric contractions can trigger intense protein synthesis
      activity at the MTJ most likely related to myofibrillogenesis associated with MTJ
      remodeling.

PMID- 10950439
TI  - Trunk muscle activation in open stance and square stance tennis forehands.
AB  - Electromyography of the trunk muscles were compared between the open and square
      stance forehand drives of 14 collegiate tennis players. Surface EMG were
      bilaterally collected from the rectus abdominis (RA), external oblique (EO), and
      erector spinae (ES) in open and square stance forehand drives. EMG data were
      transferred by telemetry, 12 bit A/D converted at 1000 Hz, and stored for
      analysis. Rectified and smoothed EMG data were normalized (NEMG) to maximal
      isometric voluntary contractions and mean NEMG were calculated during the forward
      swing and follow through phases of the stroke. A 2 x 2 x 2 x 6 factorial ANOVA
      (Gender, Stance, Phase, Muscle) with repeated measures on Subject showed
      significant (p < 0.05) effects of Gender, Muscle, Phase, and several
      interactions. The nonsignificant differences in muscle activation between stances
      did not support the belief of tennis experts that open stance forehands require
      greater trunk activation than square stance forehands. Mean NEMG of the ES were
      significantly (p < 0.05) larger than EO or RA, which was consistent with
      observations of tennis-specific strength imbalances and increasing incidence of
      low back injuries in tennis.

PMID- 10950440
TI  - Effects of a training taper on tissue damage indices, serum antioxidant capacity
      and half-marathon running performance.
AB  - This study investigated the effects of a training taper on muscle damage indices
      and performance. Two matched groups of seven male runners each performed two self
      paced half-marathons on a motorised treadmill. After the first half-marathon one
      group maintained their normal weekly training volume, while the taper group
      progressively reduced weekly training volume by 85 %. Venous blood was drawn
      immediately before and after the first half-marathon. Subsequent samples were
      taken 7 days later, immediately before and after the second half-marathon. Serum
      samples were analysed for antioxidant capacity, urate concentration and creatine
      kinase activity (CK). The plasma concentration of malondialdehyde (MDA) was used
      as a marker of lipid peroxidation. There were no differences in running
      performance either between the first and second half-marathon within each group,
      or between groups (86.75 +/- 2.65 min and 87.67 +/- 2.87 min for the "normal
      training" group vs 85.62 +/- 2.81 min and 85.39 +/- 3.52 min for the "training
      taper" group). Serum antioxidant capacity and CK were increased over time (P <
      0.05, ANOVA), with significant elevations after each half-marathon (P<0.025, t
      test). Elevations in MDA attained significance for the first half-marathon (P <
      0.05, t-test) when data for both subject groups were pooled. There were no
      differences in serum antioxidant capacity, or urate concentration between groups.
      Postexercise CK was lower following the training taper (149 +/- 22% baseline, for
      the training taper vs 269 +/- 55 % baseline for the normal training group,
      P<0.05, t-test). Despite evidence that the training taper reduced muscle damage,
      relative to the normal training group, half-marathon performance was not
      enhanced.

PMID- 10950442
TI  - The effects of exercise training intensification on glucose disposal in elite
      cyclists.
AB  - To assess the effect of training on glucose disposal, we performed a longitudinal
      study of 11 elite cyclists before and after 4 months of intensive training
      compared to 11 sedentary subjects. Insulin sensitivity (SI) and glucose
      effectiveness (Sg) were measured using Bergman's minimal model. Sg includes basal
      insulin effectiveness (BIE) and a parameter termed glucose effectiveness at zero
      insulin (GEZI). After overnight fasting glucose was administered intravenously
      (0.5 g x kg(-1), 30% solution given over 3 min), and insulin (0.02 U x kg(-1), 1 
      2U) was injected immediately after 19 min. Sg, SI and BIE, were significantly
      higher in elite cyclists both before and after training than in sedentary
      subjects (P < 0.01). However, the non-insulin-dependent component of Sg (GEZI)
      was higher only after the intensive training in the cyclists (3.31 +/- 0.67% x
      min(-1)) than in sedentary subjects (1.7 +/- 0.2% x min(-1), P < 0.02). We
      conclude that insulin sensitivity (SI) and glucose effectiveness (Sg) are higher
      in elite cyclists than in sedentary subjects and that these high and almost
      optimal values are not further improved by additional training. However, the
      improvement in GEZI, as reflected by the difference between post-training GEZI
      and sedentary control values, raises the possibility of an increase of the non
      insulin-mediated mobilization of glucose transporters.

PMID- 10950441
TI  - Adiposity, lipid levels, and brief endurance training in nonobese adolescent
      males.
AB  - Physical activity during childhood and adolescence may influence the development
      of childhood obesity and cardiovascular disease later in life. Research focused
      prospectively on the effects of training on lipid levels in nonobese subjects,
      and studies using noninvasive measurements of subcutaneous and intraabdominal fat
      are lacking. It was hypothesized in nonobese sedentary adolescent males that a
      brief endurance-type exercise training intervention would reduce body fat and
      improve lipid profiles. Thirty-eight healthy, nonobese sedentary adolescent males
      (mean age 16 +/- 0.7 years old; 18 controls, 20 trained) completed a 5-week
      prospective, randomized, controlled study. Adiposity was measured using magnetic
      resonance images of the thigh and abdomen (subcutaneous abdominal adipose tissue
      [SAAT] and intraabdominal adipose tissue [IAAT]). Lipid measurements included
      serum triglycerides (TG), total cholesterol (TC), HDL and LDL cholesterol. There
      was no change in body weight in either control or training groups. Training led
      to small but significant reductions in thigh fat (-4.6 +/- 1.5%, p < 0.03) and
      SAAT% (1.7 +/- 0.8%, p < 0.02). There was no change in IAAT%. Unexpectedly in the
      control group there were significant increases in thigh fat (5.2 +/- 1.7%,
      p<0.01), SAAT% (1.8 +/- 0.6, p < 0.007) and IAAT% (4.5 +/- 1.1, p < 0.0007).
      Training-induced changes in adiposity were not accompanied by changes in
      circulating lipids. In nonobese adolescent males a brief period of endurance
      training led to reductions in body fat depots without weight change while body
      fat increased rapidly in the control group. Exercise training did not change
      lipid levels, the latter may require more sustained alterations in patterns of
      physical activity.

PMID- 10950443
TI  - Influence of light additional arm cranking exercise on the kinetics of VO2 in
      severe cycling exercise.
AB  - This study examined the influence of light additional arm cranking exercise on
      the VO2 slow component observed during severe cycling exercise. During
      incremental tests, eleven triathletes exercised to exhaustion cycling with leg,
      cranking with arm and combined arm and leg cranking and cycling (arm work-rates
      being set at the third of leg work rates) to determine arm, leg and combined arm
      and leg lactate threshold and VO2max. After these incremental tests subjects
      performed in random order severe exercises until exhaustion at work-rates
      corresponding to the lactate threshold + 50% of the difference to the work rate
      associated with VO2max and the lactate threshold, i.e., delta50: 1) with legs
      only (leg delta50) 2) leg delta50 plus a very light arm cranking exercise at 25 %
      of the arm lactate threshold (Ldelta50 + A25). VO2 slow component was the
      increase of VO2 (in ml x min(-1)) between the third and the sixth minute of
      exercise (deltaVO2 63 min). Results showed 1) Nine of the eleven triathletes had
      a VO2 slow component in arm delta50; 2) a light cycle arm exercise (25% of
      lactate threshold) added to a severe leg cycle exercise did not decrease time to
      exhaustion in severe exercise (493 +/- 154s vs 418 +/- 84, P=0.4); 3) For the
      five subjects who had a VO2 slow component in leg cycling, the addition of a
      light arm exercise (25% of arm LT) decreased the VO2 slow component significantly
      (from 457 +/- 173 ml x min(-1) for leg delta50 to 111 +/- 150 ml x min(-1) for
      Ldelta50 + A25, Z = -2.0, P = 0.04). In conclusion, light additional arm cranking
      decreases the VO2 slow component in severe cycling. Further studies are needed to
      confirm the hypothesis that extra work due to an increasing handgrip on the
      handlebars may contribute to the VO2 slow component in cycling.

PMID- 10950444
TI  - Human skeletal muscle HSP70 response to physical training depends on exercise
      intensity.
AB  - We have previously reported that HSP70 in human skeletal muscle could be induced
      by training. However, whether HSP70 induction is dependent upon exercise volume
      or exercise intensity remains unknown. The aim of the present study was to
      investigate the relationship between HSP70 and training intensity in rowers.
      Fourteen well-trained male rowers were divided into two groups (group A, n = 6;
      group B, n = 8). Group A performed higher intensity exercise during 1st phase,
      whereas group B performed higher intensity exercise during 2nd training phase.
      Training volume in 2nd phase increased in both groups. Both training intensity
      and volume were reduced in 3rd phase. Muscle samples were taken from m. vastus
      lateralis by fine needle biopsy before training, at the end of the 1st, 2nd and
      3rd training phases. HSP70 was quantitatively determined using SDS-PAGE with
      silver stain. In group A, HSP70 increased significantly from 38 +/- 12 etag
      before training to 59 +/- 16 etag at the end of the lst training phase (loaded
      total protein 2.5microg), and decreased afterwards. In group B, HSP70 increase
      (from 36 +/- 11 etag to 50 +/- 13 etag) in the 1st phase was significantly
      smaller, there was a further increase of HSP70 in the 2nd phase (60 +/- 14 etag).
      At the end of the training, HSP70 decreased in both groups. Thus, HSP70 response
      to training seems to be dependent upon exercise intensity.

PMID- 10950445
TI  - Load carriage energy expenditure with and without hiking poles during inclined
      walking.
AB  - The purpose of this study was to compare load carriage energy expenditure with
      and without using hiking poles. Twenty male volunteers aged 20-48yr (Mean=29.8yr)
      completed two randomly ordered submaximal treadmill trials with poles (E) and
      without poles (C). Poles and load (15 kg backpack) were fitted for each subject
      according to the manufacturers' suggestions. Heart rates (HR), minute ventilation
      (V(E)), oxygen consumption (O2), caloric expenditure (Kcal), and rating of
      perceived exertion (RPE) were recorded at the end of each minute. Two trials
      separated by one week consisted of a constant treadmill speed of 1.5 mph and 1
      min at 10% grade, 2 min at 15% grade, 2 min at 20% grade, and 10 min. at 25%
      grade. Mean HR (E = 144.8 +/- 24.4 b x min(-1); C = 144.0 +/- 25.7 b x min(-1))
      and mean V(E) (E=51.4 +/- 15.8L x min(-1); C=50.8 +/- 17.0L x min(-1)), VO2 (E =
      26.9 +/- 6.1 ml x kg(-1) x min(-1); C = 27.4 +/- 6.6 ml x kg(-1) x min(-1)), and
      Kcal (E = 10.6 +/- 2.9 Kcal x min(-1); C = 10.8 +/- 3.1 Kcal x min(-1)) were not
      significantly different between the two conditions. RPE (E = 13.28 +/- 1.2; C =
      14.56 +/- 1.2) was significantly lower (P < 0.05) with hiking poles. Analysis of
      paired time points yielded no significant differences in HR, VO2, V(E), and Kcal,
      however, RPE means were significantly lower for 5 of the last 7 trial minutes
      with the use of poles. These results suggest that during load carriage on
      moderate grade, the weight and use of hiking poles does not increase energy
      expenditure but may provide reduced perceptions of physical exertion.

PMID- 10950446
TI  - Dimensional changes cannot account for all differences in short-term cycling
      power during growth.
AB  - The purpose of this study was to determine to what extent anthropometric
      characteristics account for cycling peak power during growth. Five hundred and
      six male subjects aged 7.5-18 years performed three brief maximal sprints on a
      friction-loaded cycle ergometer. Cycling peak power (CPP) was calculated
      including the flywheel inertia of the device. Fat-free mass (FFM) and lean leg
      volume (LLV) were assessed by anthropometry. Anthropometric characteristics
      increased significantly during growth (p<0.001) but plateaued from about 16 years
      of age (p > 0.3). The same pattern was observed for CPP, while the time to reach
      CPP decreased during growth. CPP correlated as highly with LLV as with FFM and
      both parameters may therefore be interchanged. However, in non weight-bearing
      exercises, such as cycling, it seems more relevant to "normalise" leg power for
      LLV. Multiple stepwise regression, using an allometric model, showed that a large
      part of the variance of CPP was explained by LLV (88.2%, p<0.001). However, age
      and time to reach peak power also contributed significantly (approximately 3 %, p
      < 0.001). The prediction of CPP revealed that FFM and age contributed to 92.2% of
      the total variance of CPP. Because of its practicability, fat-free mass is
      particularly useful in prospective studies. Although the effects of dimensional
      changes in CPP during growth are obvious, undetermined qualitative changes of
      muscle function during maturation must be considered.

PMID- 10950447
TI  - Comparison of critical swimming velocity and velocity at lactate threshold in
      elite triathletes.
AB  - The purpose of this study was to determine whether the critical swimming velocity
      (Vcrit) corresponds to the velocity at lactate threshold (V-LT) in elite
      triathletes. Eight elite triathletes (5 male, 3 female; age 26 +/- 4 years;
      height 1.7 +/- 0.1 m and body mass 75 +/- 4 kg) participated in the study. Vcrit,
      defined as the speed that could theoretically be maintained indefinitely without
      exhaustion, was expressed as the slope of a regression line between swimming
      distance covered and the corresponding times of five time trials over 100, 200,
      400, 800 and 1500m and all combinations of these. Lactate threshold (LT) was
      determined by visual inspection as the point of first inflection of the lactate
      work rate curve following 5 x 300 m swims of increasing velocity which were paced
      using the Aquapacer (Challenge and Response, Inverurie, Scotland). Velocities of
      the 300 m swims were -10, -5, 0, +5 and +10% of the average 100m pace from a 1500
      m time trial. Vcrit was similar regardless of the combination or number of time
      trials used in the linear regression. For all subjects Vcrit was significantly
      faster (p <0.05) than V-LT (1.23 +/- 0.11 m x s(-1) and 1.15 +/- 0.10 m x s(-1)
      respectively). Blood lactate concentrations were also significantly higher (p <
      0.05) at Vcrit (3.0 +/- 1.0 mM) than at LT (1.9 +/- 0.4 mM). Results from the
      present study demonstrate that Vcrit can be calculated from any two time trials
      in triathletes, however Vcrit did not represent V-LT in triathletes. Since Vcrit
      is faster than V-LT it is unlikely to be sustained indefinitely and consequently
      the notion of Vcrit should be re-evaluated in light of these findings.

PMID- 10950448
TI  - Vitamin E supplementation attenuates leakage of enzymes following 6 successive
      days of running training.
AB  - The purpose of this study was to examine whether vitamin E supplementation in
      humans would attenuate an increase of serum enzymes as an indirect marker of
      muscle damage following a sudden large increase in the running distance in a 6
      day running training or not. A randomized and placebo-controlled study was
      carried out on fourteen male runners who were supplied vitamin E (alpha
      tocopherol 1200 IU x day(-1); E) or placebo (P) 4 weeks prior to (T1) and during
      6 successive days of running training (48.3 +/- 5.7 km x day(-1), means +/- SD).
      Resting venous blood samples were obtained before maximal treadmill running, at
      T1, the day immediately before (T2), the next day (T3), and three weeks (T4)
      after the running training. Serum levels of alpha-tocopherol, lipid peroxidation
      products (thiobarbituric acid; TBA), creatine kinase (CK), lactate dehydrogenase
      (LDH), and LDH isozyme 1-5 were quantitatively analyzed. No significant
      difference was found in maximal oxygen uptake (VO2max) and maximal heart rates
      following the exhaustive exercise between the P and E group during the
      experiments. Vitamin E supplementation significantly increased serum alpha
      tocopherol (p<0.001) and decreased TBA levels (p < 0.001) compared with pre
      supplementation levels. Although serum CK and LDH activities increased
      significantly at T3 in either group, significantly lower CK (p < 0.05) and LDH (p
      < 0.001) levels were observed in the E group compared with the P group. The ratio
      of LDH1 to LDH2 (LDH1/LDH2) decreased significantly at T3 in either group
      compared with the T1 levels, since there was no significant difference in the
      LDH1/LDH2 between the P and E group throughout the experiments. These results
      indicate that vitamin E supplementation can reduce the leakage of CK and LDH
      following 6 successive days of endurance running. The protective effect of
      vitamin E against free radicals probably inhibits free-radical-induced muscle
      damage caused by a sudden large increase in the running distance.

PMID- 10950449
TI  - Spondylolysis as a cause of low back pain in swimmers.
AB  - Low back pain (LBP) has recently become a common complaint in swimmers. The
      differential diagnosis of LBP in swimmers includes muscle and ligament sprains,
      Scheuerman disease, herniated disc, facet joint injury, tumors, infections, and
      spondylolysis. Although spondylolysis or listhesis is a frequent injury in the
      athlete, mainly in weightlifters, wrestlers, gymnasts, divers and ballet dancers,
      it is infrequently reported in swimmers. We have recently encountered four
      adolescent elite swimmers who complained of low back pain and were diagnosed as
      having spondylolysis. Three of the patients were either breast-strokers or
      butterfly swimmers. Plain radiography demonstrated the lesion in two patients.
      Increased uptake in bone scan was noted in all patients. CT was performed only in
      two patients and revealed the lesion in both. One patient was diagnosed within
      two weeks, and the diagnosis in the others was deferred for 2-7 months. The
      patients were treated successfully by reducing the intensity of their training
      program and the use of a corset for at least three months. Repeated
      hyperextension is one of the mechanisms for spondylolysis in athletes as is the
      case in breast-strokers and butterfly style swimmers. LBP in swimmers should
      raise the suspicion of spondylolysis. Plain radiography and bone scan should be
      performed followed by SPEC views, CT, or MRI as indicated. If the case is of
      acute onset as verified by bone scan, a Boston or similar brace should be used
      for 3 to 6 months in conjunction with activity modification and optional physical
      therapy. Multidisciplinary awareness of low back pain in swimmers, which includes
      trainers, sport medicine physicians, and physical therapists, should lead to
      early diagnosis and appropriate treatment.

PMID- 10950450
TI  - Haemoglobin, haematocrit and red blood cell indices in elite cyclists. Are the
      control values for blood testing valid?
AB  - BACKGROUND: In international cycling and cross-country skiing competitions, blood
      tests are used to unmask the performance enhancing misuse of erythropoietin.
      Haematocrit (cycling) and haemoglobin (cross-country skiing) limits have been set
      by international sporting federations (haematocrit 50%, haemoglobin 18.5 g/dl).
      Athletes tested above these cut-off values are declared unfit for competition. To
      investigate the validity of these regulations, we studied haemoglobin,
      haematocrit and red blood cell indices of elite cyclists before erythropoietin
      became commercially available. MATERIAL AND METHODS: We investigated 523 blood
      samples of 92 male elite cyclists (age 16-31 years) from 1978 to 1987.
      Haematocrit, haemoglobin and red blood cell count were analysed automatically,
      erythrocyte indices were calculated. RESULTS: Haemoglobin (-0.3 +/- 1 g/dl),
      haematocrit (-1.2 +/- 2.8%) and red blood cell count (-0.2 +/- 0.4 x 10(6)/mm3)
      decreased significantly (p < 0.05) with increasing training workload. The
      erythrocyte indices showed no significant change. Fifty-four blood samples
      (10.3%) showed a haematocrit above 50%, one sample presented a haemoglobin mass
      higher than 18.5 g/dl. During periods of increased workload, less athletes tested
      above the haematocrit limit. CONCLUSION: The current haematocrit limit used in
      blood tests might lead to a high number of false positive tests.

PMID- 10950451
TI  - Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG
      CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is
      related to stage of infection.
AB  - The present study reports the hematopoietic response to the exogenous
      administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin
      (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage
      (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + <
      500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected
      animals exhibited significantly impaired bone marrow (BM) and peripheral blood
      (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to
      historic controls. In addition, compared to early-stage SIV-infected animals,
      late-stage SIV-infected macaques demonstrated a more marked dysfunction, as
      assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming
      unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early
      stage or late-stage SIV infection increased the viral load, as assessed by bDNA
      assay. These data suggest that hematopoietic reserve and the response to various
      cytokines is decreased even in early-stage SIV infection, with the hematopoietic
      dysfunction progressing in parallel to SIV infection.

PMID- 10950452
TI  - Microsatellite DNA variation in Bornean orangutans (Pongo pygmaeus).
AB  - Orangutans (Pongo pygmaeus) on the islands of Borneo and Sumatra are considered
      two separate subspecies. However, the genetic relationships between isolated
      populations on Borneo are not clear. This study determined the extent of
      variation within the Bornean subspecies of orangutan, using microsatellite DNA
      analysis. Blood samples were collected from 96 individuals of known origin from
      East, West and Central Kalimantan. Human microsatellite primer pairs located at
      human map position D2S141, D4S431, D 11S925, D16S420 and D17S791 were suitable
      for use in primates. D4S431 appeared monomorphic for all orangutans. In three
      cases (D2S141 East and West and D16S420 West), a highly significant excess of
      homozygous allele frequencies was detected, but with other primer pairs no
      significant difference in allele frequencies occurred. We conclude that the
      divergence between the different populations on Borneo is less than the variation
      within the populations. There was also evidence that inbreeding occurred within
      the populations.

PMID- 10950453
TI  - Use of intrauterine devices (IUDs) for contraception in the common chimpanzee
      (Pan troglodytes).
AB  - The common chimpanzee (Pan troglodytes) is a species phylogenetically very close
      to man. It was not many years ago that the captive population of chimpanzees (P.
      troglodytes) was considered at risk because of perceived problems with
      reproductive success. With the potential need for many individuals for research
      in a variety of areas, particularly in the areas of parasitic and viral
      infections, an NIH-funded program was established to promote the breeding of the
      species. That program, the 'National Chimpanzee Breeding and Research Program',
      was highly successful, so successful, in fact, that there is now a surplus of
      animals available for current research programs. This situation has prompted the
      use of intrauterine devices (IUDs) as a method of fertility control. Overall,
      this method is successful and associated with a failure (of pregnancy) rate
      similar to that reported in the human. Physical and logistic constraints,
      however, render the method less than ideal for situations where a pregnancy rate
      of zero is desired.

PMID- 10950454
TI  - The detection and monitoring of early pregnancy in the vervet monkey
      (Cercopithecus aethiops) with the use of ultrasound and correlation with
      reproductive steroid hormones.
AB  - Twenty early pregnancies were diagnosed and monitored in vervet monkeys by
      ultrasonography. Non-gravid uteri became increasingly echogenic from cycle days 7
      to 26. The first definite sign of pregnancy was a gestational cavity of 2 mm (+/-
      0.80) at 33.0 (+/- 1.48) days menstrual age, which was also used to date all
      subsequent features. Earlier signs, such as an endometrial line swelling or
      endometrial 'pregnancy' ring, as reported for other non-human primate species,
      could not be reliably and consistently used to diagnose pregnancy in vervet
      monkeys. A rapid increase of the gestational cavity size from days 37 to 49
      corresponded closely to a rapid increase in plasma progesterone concentration
      from day 39 to 49. The first yolk sac was recognizable at 38.0 days (+/- 3.10)
      and measured 3.3 mm (+/- 0.40) in diameter. A heart beat could be detected at
      45.5 (+/- 1.73) days and the size of the first measurable embryo at 35 days was 2
      mm. The dating of most features was within the range reported for other non-human
      primate species.

PMID- 10950455
TI  - Ultrasonography of the normal kidney in the cynomolgus monkey (Macaca
      fascicularis): morphologic and Doppler findings.
AB  - The purpose of this study was to obtain sonographic measures of normal kidneys in
      cynomolgus monkeys (Macaca fascicularis). The kidneys of 27 healthy female
      cynomolgus monkeys were examined with two-dimensional, duplex and power Doppler
      under sedation or general anesthesia. Except for shape and sinus echogenicity,
      the kidneys of the cynomolgus monkey are morphologically similar to those of
      humans. Left kidney volume estimations (mean, 5.1 cm3) were significantly smaller
      (P<0.001) than those of the right (mean, 5.9 cm3), and both increased
      significantly with increasing body weight (P<0.05, r = 0.408). The mean resistive
      index (RI) of ketamine-sedated monkeys was 0.54, with an upper limit of 0.74 for
      the renal artery. The mean RI under general anesthesia was 0.65, with an upper
      limit of 0.77. Morphologic and Doppler ultrasound assessments of the kidneys can
      be consistently performed in the conscious cynomolgus monkey, and anesthesia can
      have hemodynamic effects that alter the Doppler arterial waveform.

PMID- 10950456
TI  - Chemotherapy of haemobartonellosis in squirrel monkeys (Saimiri sciureus).
AB  - Splenectomised Saimiri sciureus squirrel monkeys are being used increasingly as
      an experimental host for human malarial studies, notably for the assessment of
      candidate vaccines against Plasmodium falciparum blood-stage infection. Recently,
      we have reported that colony-reared S. sciureus monkeys are asymptomatic carriers
      of Haemobartonella sp. and that patent Haemobartonella infection, activated
      following splenectomy, may interfere with the course of P. falciparum
      parasitaemia in these animals. For several years, splenectomised S. sciureus
      monkeys were routinely submitted to oxytetracycline therapy before their use in
      malarial studies in order to prevent a possible spontaneous Heamobartonella
      infection. However, we report here that such antibiotic therapy is often
      ineffective and that neoarsphenamine chemotherapy may be considered as an
      alternative to cure both latent and patent haemobartonellosis in S. sciureus
      monkeys.

PMID- 10950457
TI  - Autoimmune hemolytic anemia (AIHA) in an infant rhesus macaque (Macaca mulatta).
AB  - Autoimmune hemolytic anemia (AIHA) is a disorder associated with the destruction
      of red blood cells (RBCs) by autoantibodies. We report a rare case of AIHA in an
      infant rhesus macaque (Macaca mulatta) which received a continuous administration
      of four drugs, a dopamine agonist. dopamine receptor inhibitor, and two gamma
      aminobutyric acid receptor inhibitors into the brain during the course of
      neurophysiological experiments. The main clinical findings were severe anemia and
      splenomegaly. Hematological and serological examinations revealed the appearance
      of peripheral erythroblasts and autoantibodies against RBCs. Medical treatments,
      including washed RBC transfusion and corticosteroids, transiently improved the
      animal's anemia, but euthanasia was decided on 331 days after the start of the
      experiment. The pathological findings revealed severe anemia, splenomegaly, and
      extramedullary hematopoiesis in the liver and kidneys. These findings and the
      clinical course suggest that this anemia was a warm-antibody type of AIHA induced
      by the administration of the drugs for the neurophysiological experiment.

PMID- 10950458
TI  - Esophageal cancer prevention, cure, and palliation.
AB  - Adenocarcinoma of the esophagus and gastric cardia are the most rapidly
      increasing cancers in developed countries. Adenocarcinoma of the esophagus is
      associated with chronic gastroesophageal reflux, and Barrett's esophagus is a
      precursor. This disease most frequently affects middle-aged white men. Endoscopic
      surveillance should be performed on patients with Barrett's esophagus, and
      esophagectomy is often performed on persons with high-grade dysplasia. Ablation
      of Barrett's esophagus has been proposed to prevent cancer but the outcomes are
      unproven. Squamous carcinoma of the esophagus most often affects black men and is
      associated with alcohol and tobacco use. The diagnosis of esophageal cancer is
      made by endoscopy with biopsy. Optimal staging is with endoscopic ultrasonography
      for depth of invasion and regional nodes and CT scanning for distant metastases.
      Neoadjuvant chemotherapy and radiation therapy followed by surgery is widely
      practiced, but survival benefits remain to be proven. Palliation of dysphagia may
      be achieved with surgery, radiation therapy, or endoscopic means, with the latter
      having fewer complications.

PMID- 10950459
TI  - Helicobacter pylori, gastric MALT lymphoma, and adenocarcinoma of the stomach.
AB  - The discovery of Helicobacter pylori and its relationship to upper
      gastrointestinal tract diseases has emphasized the significance of infectious
      pathogens in clinical disease. Severe manifestations of H. pylori-associated
      diseases include gastric adenocarcinoma and the recently described gastric mucosa
      associated lymphoid tissue (MALT) lymphoma. Ongoing worldwide investigations of
      the interactions of H. pylori and the host response are rapidly clarifying the
      role of this bacterium in multiple gastrointestinal diseases. This review will
      address diagnosis, management, and follow-up of the patient presenting with
      gastric MALT lymphoma, including a discussion of the issues related to
      premalignant lesions associated with gastric adenocarcinoma. Prospective trials
      and long-term follow-up studies are in progress and will guide appropriate
      management of these diseases.

PMID- 10950460
TI  - Diet, lifestyle, and colon cancer.
AB  - Diet and lifestyle modification offers means of reducing risk of developing colon
      cancer. Current data suggest that consuming a Western style diet, that is, one
      high in meat, refined grains, and sugar and low in vegetables and fiber, may
      contribute to risk of colon cancer. There also are data to support a reduction in
      colon cancer risk from consuming high levels of calcium and folate. Energy
      balance and maintaining an appropriate body weight have been associated with a
      reduced risk of colon cancer. An important part of the energy balance equation is
      physical activity. High levels of physical activity have consistently been
      identified as being associated with a reduced risk of colon cancer. It is
      estimated that 13% of colon cancer can be attributed to being physically
      inactive, 12% of colon cancer can be attributed to eating a Western style diet,
      and 8% of colon cancer can be attributed to having a first degree relative with
      colorectal cancer.

PMID- 10950461
TI  - Rare syndromes and genetic testing for colorectal cancer.
AB  - The genes responsible for each of the inherited syndromes of intestinal polyposis
      and colorectal cancer are now known. This knowledge has led to genetic testing
      for syndrome diagnosis and for determining which persons in an affected family
      actually have the condition. Genetic testing has also allowed a more precise
      clinical characterization of each of the syndromes and their subtypes. Optimal
      application of genetic testing, proper cancer prevention, and management of
      nonmalignant features of each of the syndromes are the next goals. This report
      summarizes each of the syndromes, their genetics, and management and provides an
      approach for genetic testing.

PMID- 10950462
TI  - Postoperative management of local colorectal cancer: therapy and surveillance.
AB  - Adjuvant therapy is widely recommended for stage III colon cancer and stages II
      and III rectal cancer. Although fluorouracil-based regimens are standard, newer
      agents either alone or in combination may improve response rates. Although nearly
      all patients enter a postoperative surveillance program after surgical resection,
      the clinical effectiveness of such surveillance, which is not standardized, is
      questionable. Critical review of the use of different components (laboratory,
      radiographic, and endoscopic) of these programs finds little support for
      intensive surveillance.

PMID- 10950463
TI  - Carcinoid tumors.
AB  - Carcinoid tumors most commonly occur in the gastrointestinal tract and are known
      best for the bizarre manifestations of the carcinoid syndrome caused by the
      release of tumor products. However, many carcinoid tumors do not present with or
      cause the carcinoid syndrome, and this has led to the development of new
      diagnostic markers for these tumors. New treatments have emerged recently and are
      being developed, because although these tumors are relatively indolent, they can
      metastasize. The biology of carcinoid tumors of the gastrointestinal tract can be
      classified in large part by the embryologic regions of the gut in which they
      occur. More carcinoid tumors will be discovered as the indications and use of
      gastrointestinal endoscopies increase, so the diagnosis and initial management of
      carcinoid tumors will fall largely on the gastroenterologist.

PMID- 10950464
TI  - New developments in pancreatic cancer.
AB  - Adenocarcinoma of the pancreas is the fifth most common cause of cancer death in
      the United States. It affects men and women fairly equally and is most frequently
      diagnosed in the eighth decade of life. It may occur as part of
      hereditary/familial pancreatitis with an identified genetic mutation, and smokers
      are at increased risk. Cancer most often occurs in the pancreatic head and often
      leads to biliary obstruction with a clinical presentation of painless jaundice.
      The principal diagnostic modality is dedicated pancreatic computed tomography
      (CT) scanning, although other imaging techniques have a role. Endoscopic
      retrograde cholangiopancreatography (ERCP) is generally reserved for obtaining
      tissue, for which it is insensitive, or for palliative stenting. Surgery with the
      Whipple procedure offers the only chance of cure. Patients are staged as
      resectable if there are no distant metastases to lymph nodes or organs and there
      is no major vessel involvement. The 5-year survival rate for resectable patients
      is about 10% with a median survival of 12 to 18 months. Unresectable patients
      live about 6 months. Adjuvant chemotherapy with 5-fluorouracil (5-FU) or
      gemcitabine provides modest benefits. Palliative biliary decompression, pain
      control, and maintenance of gastric drainage are the usual forms of therapy.

PMID- 10950465
TI  - Diagnosis and therapy of biliary tract malignancy.
AB  - Bile duct and gallbladder cancer are relatively uncommon. Predisposing factors
      include primary sclerosing cholangitis and gallstones larger than 3 centimeters.
      Patients present with signs of biliary obstruction and cholestasis. A serum CA 19
      9 elevated above 100 U/mL is a useful marker. The diagnosis is implied on imaging
      studies and confirmed by tissue obtained at endoscopic retrograde
      cholangiopancreatography or surgery, or by the clinical course. Surgery is the
      only curative therapy and survival is improved with resection of early stage
      disease. Endoscopic or percutaneous transhepatic stenting provides effective
      palliation. Generally, survival is less than 1 year.

PMID- 10950466
TI  - Newer antidepressants: further reflections.

PMID- 10950467
TI  - Desipramine versus phenelzine in recurrent unipolar depression: clinical
      characteristics and treatment response.
AB  - We compared desipramine with phenelzine in a double-blind, parallel-groups study
      of 43 outpatients with recurrent unipolar depression. Response to the two drugs
      was similar, with an overall average reduction in scores on the Hamilton Rating
      Scale for Depression of about 50% over 6 weeks. Improvement was negatively
      correlated with initial severity of depression, especially in patients treated
      with desipramine. Response to desipramine was better in patients with moderate to
      severe stressors and no previous hospitalizations. Response to either treatment
      was better in patients whose course consisted of recurrent depressions with a
      stable baseline, even if the baseline was dysthymic.

PMID- 10950468
TI  - Paranoid/belligerence and neuroleptic dosage in newly admitted schizophrenic
      patients.
AB  - The aim of this study was to determine if the severity of paranoid/belligerence
      was a major determinant of neuroleptic dosage in newly admitted patients with
      acute or exacerbated schizophrenia. Two clinical psychiatrists, who had no
      clinical responsibility for drug treatment and were blind to neuroleptic dosage
      regimens, jointly interviewed 155 patients who were cooperative enough to be
      carefully interviewed with the Structured Clinical Interview for the DSM-III-R,
      Positive and Negative Syndrome Scale (PANSS) Edition. The large majority of the
      patients were receiving moderate dosages of neuroleptics (mean peak dosage: 500
      mg/day of chlorpromazine equivalents). There was a positive correlation between
      the score on the PANSS paranoid/belligerence cluster and the daily dosage of
      neuroleptic treatment. Splitting the sample by gender, the correlations remained
      highly significant. In a multivariate analysis controlling for the effects of
      other clinical variables, paranoid/belligerence and gender emerged as significant
      predictors of neuroleptic dosage. Clinicians prescribed lower doses of
      neuroleptics for female patients and higher doses for patients with higher
      ratings on the PANSS paranoid/belligerence cluster. These findings suggest that
      clinicians' strategy of increasing neuroleptic dosage at the manifestation of
      hostility is not limited to assaultive or uncooperative schizophrenic patients
      who are on very high dosages of neuroleptics.

PMID- 10950469
TI  - A controlled trial of amantadine hydrochloride and neuroleptics in the treatment
      of tardive dyskinesia.
AB  - An 18-week, double-blind, crossover study of amantadine and neuroleptics in the
      treatment of tardive dyskinesia (TD) is described. A fixed-dose regimen was used,
      and objective rating scales for TD, extrapyramidal symptoms, and mental state
      were employed. The results indicate that amantadine is significantly better than
      placebo in the management of TD and that there is little risk of exacerbating
      psychosis. Further investigation of this potentially useful medication is
      warranted.

PMID- 10950470
TI  - Carbamazepine augmentation in lithium-refractory bipolar patients: a prospective
      study on long-term prophlyactic effectiveness.
AB  - Twenty-two patients affected by bipolar or schizoaffective disorder, in whom
      carbamazepine was added to lithium after recurrence when on maintenance with
      lithium alone, were followed up prospectively for 2 to 13 years. The number of
      episodes, hospitalizations, and cumulative affective morbidity was markedly
      reduced after carbamazepine augmentation. Seventeen patients presented a better
      course during combined treatment than during lithium alone, and of these 15 had
      no further recurrences. Four patients did not appear to improve after
      carbamazepine augmentation, whereas one featured reemergence of affective
      episodes after having derived satisfactory benefit from combination for 7 years
      (delayed tolerance). Carbamazepine augmentation was associated with a reduction
      of lithium doses in some patients, including a subgroup who had not tolerated
      lithium at usual therapeutic levels. Carbamazepine significantly reduced serum
      thyrotropin concentrations, which were abnormally high in approximately one half
      of patients when on lithium alone. Total serum thyroxine concentrations were also
      decreased after carbamazepine augmentation, but free thyroid hormone
      concentrations did not change. Other significant carbamazepine-induced changes in
      laboratory tests included increases in total cholesterol concentrations and
      decreases in white blood cell counts.

PMID- 10950471
TI  - Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon
      dioxide hypersensitivity in panic patients: a double-blind, random, placebo
      controlled study.
AB  - The effects of short treatment (7 days) with the tricyclic antidepressant
      imipramine and the two selective serotonin reuptake inhibitors paroxetine and
      sertraline on the reactivity to inhalation of 35% CO2/65% O2 were compared in 70
      panic patients who had positive responses to 35% CO2 inhalations. A double-blind,
      random, placebo-controlled design was applied. Each patient was given the 35% CO2
      challenge on days 0 (before starting the treatment), 3, and 7. In the placebo
      group, there were no significant changes in the reactivity to 35% CO2 in the
      three sessions whereas there were significant similar reductions of reactivity to
      35% CO2 in all three drug-treated groups. These results confirm the good
      reproducibility of 35% CO2 reactivity and the negligible effects of placebo on
      reactivity to CO2 and suggest that short treatments with imipramine, paroxetine,
      and sertraline decrease reactivity to 35% CO2, possibly as an expression of their
      antipanic properties.

PMID- 10950472
TI  - CYP2D6 inhibition in patients treated with sertraline.
AB  - Sertraline, a selective serotonin reuptake inhibitor used to treat depression,
      inhibits CYP2D6 in vitro (Ki = 1.2 microM) less potently than fluoxetine (Ki =
      0.15 microM). To determine the extent and time course of CYP2D6 inhibition in
      patients, six males (mean age: 40 years, range: 29-64 years), who were starting
      treatment for depression with sertraline, were phenotyped on five occasions (once
      before treatment and approximately 3, 7, 14, and 21 days later). Phenotype status
      was determined using oral dextromethorphan (30 mg) by calculating the urinary
      ratio of O-demethylated metabolites to parent drug (i.e., log ODMR). CYP2D6
      genotype was determined by leukocyte DNA analysis using polymerase chain reaction
      amplification. Compliance was confirmed by sertraline plasma levels. Daily
      sertraline dosages ranged from 50 to 150 mg. Genotype results indicated all
      subjects were extensive metabolizers (four homozygous wild type [wt], two
      heterozygous wt/B mutation). Phenotype results showed that CYP2D6 inhibition in
      patients treated with sertraline appeared to be related to baseline CYP2D6
      activity and sertraline dosage. Some patients with high CYP2D6 activity can
      demonstrate inhibition with sertraline dosages as low as 50 mg.

PMID- 10950473
TI  - Elevated serum phenytoin concentrations associated with coadministration of
      sertraline.
AB  - The hepatic cytochrome P450 enzyme system is involved in the metabolism of
      numerous drugs. Specific enzymes are associated with the metabolism of specific
      drugs. The potential for drug interactions arises when one drug inhibits or
      induces the enzyme(s) responsible for metabolism of another drug given
      concurrently. Most psychotropics are metabolized by these enzymes. Clinically
      significant drug interactions are reported between the selective serotonin
      reuptake inhibitors and other psychotropics. Specifically, interactions between
      fluoxetine and phenytoin are reported with substantial elevations of phenytoin
      concentrations. Phenytoin is metabolized by the CYP2C subfamily, and fluoxetine
      is known to inhibit this subfamily. Similarly, sertraline also inhibits the CYP2C
      subfamily, but no case reports to date have been identified. To minimize and
      prevent these interactions, one must be aware of the P450 enzymes involved in
      drug metabolism. The significance of these interactions seems to rely both on the
      concentration of the drug at the enzyme and its potency for inhibiting the
      enzyme. Frequent monitoring of serum concentrations of drugs with a narrow
      therapeutic range would be appropriate when a potential inhibitor is added. This
      article describes an apparently similar interaction between sertraline and
      phenytoin in two elderly patients, which resulted in elevated phenytoin
      concentrations without symptoms of toxicity.

PMID- 10950474
TI  - Lack of effect of fluoxetine on the hypoprothrombinemic response of warfarin.
AB  - The purpose of this study was to assess the effect of fluoxetine on the
      hypoprothrombinemic response of warfarin in patients chronically anticoagulated.
      Patients receiving low-intensity anticoagulation with warfarin were recruited.
      All patients were taking stable dosages of warfarin and had two baseline
      prothrombin times (PTs) within 10% of each other. Each patient received
      fluoxetine (20 mg daily) for 21 days. PTs were measured on days 2, 5, 8, 12, 15,
      19, and 22 of fluoxetine administration. Six patients completed the study. There
      was no significant difference in mean PTs before and during fluoxetine
      administration. Fluoxetine at the dosage studied does not predictably effect the
      hypoprothrombinemic response of warfarin.

PMID- 10950476
TI  - A possible bupropion and imipramine interaction.

PMID- 10950475
TI  - Fluvoxamine and fluoxetine do not interact in the same way with the metabolism of
      the enantiomers of methadone.
AB  - Six and seven addicts treated with racemic methadone (MTD) were comedicated with
      fluvoxamine (FLV) and fluoxetine (FLX), respectively. The plasma concentrations
      of both (R)- (the active enantiomer) and (S)-MTD were increased by FLV, whereas
      only (R)-MTD concentrations were increased by the addition of FLX. This suggests
      that cytochrome P450IID6 (CYP2D6), an enzyme that is strongly inhibited by FLX,
      preferentially metabolizes (R)-MTD, whereas CYP1A2, which is strongly inhibited
      by FLV, metabolizes both enantiomers. The choice of a selective serotonin
      reuptake inhibitor in depressive addicted patients treated with MTD and the
      possible use of FLX or FLV to potentiate the effects of MTD in some cases of
      therapeutic failure are discussed.

PMID- 10950477
TI  - Interaction of sertraline with clozapine.

PMID- 10950478
TI  - Hepatic encephalopathy associated with combined clozapine and divalproex sodium
      treatment.

PMID- 10950479
TI  - Antipsychotic blood concentrations: nonstandardization of reference ranges.

PMID- 10950480
TI  - Commentary: therapeutic monitoring of antipsychotic drugs.

PMID- 10950481
TI  - Clozapine in treatment of bromocriptine-induced psychosis.

PMID- 10950482
TI  - Serotonin syndrome treated with chlorpromazine.

PMID- 10950483
TI  - Lithium-TCA combination treatment of psychotic depression: comparison with TCA
      neuroleptic treatment.

PMID- 10950484
TI  - Atrial ectopics with clozapine-risperidone combination.

PMID- 10950485
TI  - Risperidone in the treatment of delusional parasitosis: a case report.

PMID- 10950486
TI  - Risperidone for the treatment of psychosis associated with neurosarcoidosis.

PMID- 10950487
TI  - Risperidone-associated priapism.

PMID- 10950488
TI  - Risperidone in treatment of choreoathetosis of Huntington's disease.

PMID- 10950490
TI  - Clonidine dependence.

PMID- 10950489
TI  - Nefazodone and hypotension: complication or coincidence.

PMID- 10950491
TI  - Reversible choreiform dyskinesia and extrapyramidal symptoms associated with
      sertraline therapy.

PMID- 10950492
TI  - Decrease of valproic acid concentration in the blood when coprescribed with
      fluoxetine.

PMID- 10950493
TI  - Comments on "Manic episode and ginseng: report of a possible case".

PMID- 10950494
TI  - Gabapentin for treatment of bipolar and schizoaffective disorders.

PMID- 10950495
TI  - 5-HT3 receptors, nausea, and serotonin reuptake inhibition.

PMID- 10950496
TI  - Community-based service delivery in rehabilitation: the promise and the paradox.
AB  - PURPOSE: According to many researchers, rehabilitation is being prevented from
      developing as a distinct profession due to two major problems. First, it has been
      claimed that rehabilitation is in need of a professional identity and a sense of
      cohesion if it is to emerge as a discipline. Second, it has been recognized that
      there is a need for a rehabilitation framework to challenge the restorative
      approach that continues to dominate rehabilitation, linking it back to the
      medical model from which it has attempted to escape. The model of community-based
      rehabilitation (CBR) is offered as a model that can provide the impetus for an
      attitudinal shift from the restorative tradition and unite rehabilitation workers
      through a cohesive framework. METHOD: Unfortunately, the implementation of
      community-based rehabilitation in urban societies has been disappointing. The
      current paper is a conceptual discussion of community-based rehabilitation that
      explores some potential causes of this poor implementation. RESULTS: To some
      extent, the implementation failure of community-based rehabilitation can be
      attributed to the paradoxes that are inherent in its fundamental constructs
      empowerment and community inclusion. These paradoxes occur at a conceptual level,
      a practical level and a contextual level. CONCLUSIONS: Some solutions are offered
      to enable the paradigm to be implemented more fully. In particular, it is
      suggested that there is a need to develop useful working definitions of these
      constructs, favourable attitudes among rehabilitation workers and a focus on
      community development.

PMID- 10950497
TI  - Reliability of the relative's questionnaire for assessment of outcome after brain
      injury.
AB  - PURPOSE: The relative's questionnaire (RQ) was developed to assess outcome after
      brain injury. The present study investigated its test-retest reliability when
      used in a postal survey. METHOD: Hospital records were used to identify and
      contact 288 surviving patients treated for brain injury five to seven years
      earlier. Patients were sent a copy of the RQ (RQ1) and one month later a second
      copy (RQ2) was sent to those who returned RQ1. RESULT: Two hundred and eleven
      patients were successfully contacted, of whom 128 (61%) returned RQ1, and 94 of
      these (73%) returned RQ2. The reliability of items was variable, with most having
      a kappa value of > 0.6 suggesting 'substantial agreement' or better. CONCLUSION:
      The data presented suggest that the RQ is a reliable instrument in collecting
      outcome information in brain-injured patients by postal survey. Further research
      is recommended to test the suitability of the RQ for the use as a telephone
      interview.

PMID- 10950498
TI  - A retrospective analysis of outcome in severe Guillain-Barre syndrome following
      combined neurological and rehabilitation management.
AB  - PURPOSE: To determine the outcome in severe Guillain-Barre syndrome following
      combined neurological and rehabilitation management using standardized disability
      and handicap measures and to identify the factors which affect this outcome.
      METHODS: A retrospective study was performed of 24 patients with Guillain-Barre
      Syndrome admitted over a 3 year period to the neurological rehabilitation unit of
      the National Hospital for Neurology and Neurosurgery. Queen Square, London.
      Disability and handicap on admission and discharge were measured using the
      modified Barthel Index (BI), Functional Independence Measure (FIM). Environmental
      Status Scale (ESS) and Handicap Assessment Scale (HAS). Data was collected to
      identify any factors affecting outcome; age at onset, time to nadir, duration of
      ventilation, total in-patient stay, duration of stay at the neurological
      rehabilitation unit, symptoms, signs and electrophysiological findings. RESULTS:
      The majority of patients had multiple problems. Outcome was related to the
      duration of rehabilitation. The mean modified BI score and the FIM score
      increased whereas ESS scores and HAS scores decreased, these changes were
      compatible with a reduction in disability and handicap. CONCLUSIONS: Significant
      improvement in function occurred during rehabilitation. These changes can be
      demonstrated using standardized outcome measures.

PMID- 10950499
TI  - Inferring quality of life from performance-based assessments.
AB  - PURPOSE: Performance based measures have been suggested as an approach to
      estimate quality of life, but the associations have not been extensively
      evaluated. This study's purpose was to determine the associations between quality
      of life and performance based assessments of disablements in community dwelling
      individuals post-stroke. METHODS: Forty five people were evaluated in a cross
      sectional pilot study. The subjects' quality of life (SF-36), ability in basic
      and instrumental activities of daily living (ADL), manual dexterity, mobility,
      neurological impairment, and perception of lateral neglect were evaluated.
      Multiple regression was employed to find the strongest associations. RESULTS:
      Neurological impairment explained 34% of the variation in the women's physical
      health summary score (PCS) of the SF-36. Instrumental ADL and neurological
      impairment together explained 66% of the women's mental health summary score
      (MCS) of the SF-36. Manual dexterity of the hemiplegic hand explained 39% of the
      variation in the men's PCS. CONCLUSION: Performance based measures may be useful
      to estimate quality of life in non-communicative individuals.

PMID- 10950500
TI  - Evaluation of ambulatory performance of the arm propelled three-wheeled chair
      using heart rate as a control index.
AB  - PURPOSE: The Arm propelled three wheeled chair (APTWC) is in common use in the
      economically poor countries for outdoor ambulation, the propulsion force of which
      is exerted by arm cranking in asynchronous fashion. The purpose of the study was
      to assess the ambulatory performance of the users of the device using heart rate
      as a control index, at graded speeds. METHOD: Fifteen regular users of APTWC male
      with paraplegia and poliomyelitis were ambulated at seven different graded speeds
      in outdoor settings and the resting and ambulatory heart rate was measured during
      steady state and then physiological cost index and comfortable speed of
      propulsion was computed. RESULTS: The physiological strain, linear regression of
      the relationship between heart rate and speed with correlation coefficient of r =
      0.86 (p < 0.001), polynomial regression of the relationship between physiological
      cost index (PCI) and speed with correlation coefficient of r = 0.83 (p < 0.001)
      and comfortable speed of propulsion (120 m/min) was reported. CONCLUSIONS: Heart
      rate can be used to evaluate the ambulatory performance of the device,
      quantifying energy economy for outcome evaluation and decision making for
      clinical recommendation.

PMID- 10950501
TI  - 'Is this what life is going to be like?' The story of a 34 year old man (T) who
      suffered a severe head injury after a fall.
AB  - Imagine this. You don't remember but you fell from a ladder, a distance of 20 ft
      onto concrete, on Christmas eve whilst cleaning windows. You suffered a severe
      head injury and emerged from a coma four weeks later yelling and fighting
      thinking that you are back in the Falklands. After 6 months in a specialist
      neurological unit, where you were for a majority of the time 'as unhelpful as
      possible', you are finally discharged home and your rehabilitation is 'complete'.
      You believed that your body would 'jump out of bed and go home' months ago but
      'it did not respond to your orders'. This was the beginning of a 'long and
      painful journey back to a reasonable life'. Home was not the safe and loving
      environment that you thought it would be. Everyone was beginning to see that life
      was not going to be the same again. There was conflict and distress. wife: He was
      a vibrant, energetic physical man and now he is a shell of himself. All his anger
      and frustration he feels about his injury he is taking out on us and whilst we
      all feel compassion and sympathy for him, it's hard to take... The physical
      problems are easy to deal with but it is the psychological problems that are
      hardest. son: He has changed alot. He is more short tempered and we can't reason
      with him. Anything we say is classed as arguing. He won't let us give our views
      on matters. He's always right.

PMID- 10950502
TI  - The function of the proteasome system in MHC class I antigen processing.

PMID- 10950503
TI  - [Summaries from the annual reunion of the National Aerobiology Surveillance
      Network (RNSA). Part 2].

PMID- 10950504
TI  - 2nd Joint INRA-RRI Gastrointestinal Tract Microbiology Symposium. Clermont
      Ferrand, France, 25-26 May 2000. Abstracts.

PMID- 10950505
TI  - Gamma-hydroxybutyric acid: a neurotransmitter, a medicine, a drug of abuse.
      Proceedings of the 8th Congress of the Italian Society on Biological Psychiatry.
      Naples, Italy, September 29-October 3, 1998.

PMID- 10950506
TI  - 135th Meeting of the Society of British Neurological Surgeons. Cork, United
      Kingdom, 31 August-3 September 1999. Abstracts.

PMID- 10950507
TI  - Recombinant animal cells: risk assessment and containment.

PMID- 10950508
TI  - Biotechnological applications of lab-chips and microarrays.

PMID- 10950509
TI  - How do you find new drugs using polypeptide display?

PMID- 10950510
TI  - Bioencapsulation within synthetic polymers (Part 1): sol-gel encapsulated
      biologicals.
AB  - Since its inception a decade ago, sol-gel encapsulation has opened up an
      intriguing new way to immobilize biological materials. An array of substances,
      including catalytic antibodies, DNA, RNA, antigens, live bacterial, fungal, plant
      and animal cells and whole protozoa, have been encapsulated in silica, metal
      oxide, organosiloxane and hybrid sol-gel polymers. The advantages of these
      'living ceramics' might give them applications as optical and electrochemical
      sensors, diagnostic devices, catalysts, and even bioartificial organs. With rapid
      advances in sol-gel precursors, nanoengineered polymers, encapsulation protocols
      and fabrication methods, this technology promises to revolutionize
      bioimmobilization.

PMID- 10950512
TI  - Public health scientists honor Jack C. Smith.

PMID- 10950511
TI  - The potential impact of alteration in preload on the myocardial performance index
      (MPI)

PMID- 10950513
TI  - Anaesthetic Research Society, Liverpool meeting, March 23-24, 2000. Abstracts.

PMID- 10950514
TI  - Proceedings of the 1st International Symposium on Mechanobiology: Cartilage and
      Chondrocyte. Sainte-Maxime, France, 28 August 1999.

PMID- 10950515
TI  - Leukemic meningitis in B-cell chronoc lymphocytic leukemia: resolution following
      intrathecal methotrexate.

PMID- 10950516
TI  - Absence of host-derived cells in the blood of patients in remission after
      allografting for chronic myeloid leukemia.

PMID- 10950517
TI  - No evidence for persistence of BCR-ABL-positive cells in patients in molecular
      remission after conventional allogenic transplantation for chronic myeloid
      leukemia.

PMID- 10950518
TI  - Models for actin filament organization in the erythrocyte membrane skeleton.

PMID- 10950519
TI  - [The Alpbach Public Health Conference 1997. Proceedings].

PMID- 10950520
TI  - Concerns about immunisation. Breast feeding should be promoted.

PMID- 10950521
TI  - Concerns about immunisation. Is vaccination cause celebe or bete noir?

PMID- 10950522
TI  - Concerns about immunisation. Facts are not enough.

PMID- 10950523
TI  - Hyperbaric oxygen in carbon monoxide poisoning. Authors of study clarify points
      that they made.

PMID- 10950524
TI  - Hyperbaric oxygen in carbon monoxide poisoning. 100% oxygen is best option.

PMID- 10950525
TI  - Investigations of doctors by General Medical Council. Expert witnesses who are
      out of step should be named and shamed.

PMID- 10950526
TI  - Investigations of doctors by General Medical Council. Procedure for consent still
      leaves much to be desired.

PMID- 10950527
TI  - Risk assessment of left ventricular systolic dysfunction in primary care. Drug
      treatment might be contaminating factor.

PMID- 10950528
TI  - Ethnic minorities have specific needs with regard to cardiovascular risk.

PMID- 10950529
TI  - Career development in public health. Doctors should lead public health
      departments.

PMID- 10950530
TI  - Allocating prescribing budgets. Limitations of formula should have been stated
      more clearly.

PMID- 10950531
TI  - Career development in public health. Career choice in public health should be
      less restricted.

PMID- 10950532
TI  - Allocating prescribing budgets. All prescribers in primary care groups need to
      collaborate.

PMID- 10950533
TI  - Lord, protect me from my friends. Also my experience.

PMID- 10950534
TI  - Sexual health through leadership and "sanuk" in Thailand.

PMID- 10950535
TI  - Commentary: Congenital toxoplasmosis--further thought for food.

PMID- 10950536
TI  - Is it time for a new definition of general practice? General practitioners
      specialize in their patients.

PMID- 10950537
TI  - Is it time for a new definition of general practice? General practitioners' main
      interest is people.

PMID- 10950538
TI  - Is it time for a new definition of general practice? Applying science of
      collectives to individual people results in paradox.

PMID- 10950539
TI  - Risk in cardiovascular disease. Merit of using risk reduction rather than
      absolute risk for lipid lowering drugs.

PMID- 10950541
TI  - Risk in cardiovascular disease. Absolute cardiovascular risk is not most
      appropriate measure to use.

PMID- 10950540
TI  - Risk in cardiovascular disease. Joint British societies recommend their computer
      program for risk calculations.

PMID- 10950542
TI  - Risk in cardiovascular disease. Having so many different guidelines about
      reducing risk is confusing.

PMID- 10950543
TI  - Risk in cardiovascular disease. Subclinical hypothyroidism is risk factor for
      coronary heart disease.

PMID- 10950544
TI  - Comparison of methods of estimating coronary risk. Authors did not use latest
      version of Sheffield table.

PMID- 10950545
TI  - Preventing neural tube defects. Analysis is less than thorough.

PMID- 10950546
TI  - Preventing neural tube defects. Government needs to take action.

PMID- 10950547
TI  - Psychiatric home treatment. Vigorous, well designed trials are needed.

PMID- 10950548
TI  - Psychiatric home treatment. Home treatment works.

PMID- 10950549
TI  - Psychiatric home treatment. Treatment at home is nationwide and successful.

PMID- 10950550
TI  - Special clinics are inappropriate for treating depression.

PMID- 10950551
TI  - Data on effect of HRT on breast cancer conflict with other data.

PMID- 10950553
TI  - Pursuing patients who don't pay.

PMID- 10950552
TI  - Lack of new drugs for tropical disease should not be accepted.

PMID- 10950554
TI  - Nurse staffing agencies--no gouge about it.

PMID- 10950556
TI  - Interpretation services--a question in Quechua.

PMID- 10950555
TI  - Financing--IRS eyes deals.

PMID- 10950557
TI  - Workers learn to save lives--BERT to the rescue.

PMID- 10950558
TI  - Pharmacy job market--just say please to druggists.

PMID- 10950559
TI  - Design & construction--ER on the fast track.

PMID- 10950561
TI  - Drug sampling software--follow those pills.

PMID- 10950560
TI  - Should there be parity in mental health coverage?

PMID- 10950562
TI  - Kids' ambulance--a less scary trip.

PMID- 10950563
TI  - The ASM in the new millennium.

PMID- 10950564
TI  - [International conference on the defense of people from the effect of
      electromagnetic fields].

PMID- 10950565
TI  - Concerns about a caffeine-based liposome cream.

PMID- 10950566
TI  - A comparison of hair growth between follicular-unit grafts trimmed "skinny" vs.
      "chubby".

PMID- 10950567
TI  - Emergent diagnosis of malignant melanoma through frozen section.

PMID- 10950568
TI  - More on spontaneous healing of Mohs wounds.

PMID- 10950569
TI  - Split-thickness graft harvesting tricks.

PMID- 10950570
TI  - Graft survival and cell culture medium.

PMID- 10950571
TI  - Linear basal cell carcinomas.

PMID- 10950572
TI  - Water temperature changes.

PMID- 10950573
TI  - Lasers in treatment of Pseudofolliculitis barbae.

PMID- 10950574
TI  - Fibers after CO2 laser resurfacing.

PMID- 10950575
TI  - Nothing like a little science now and then.

PMID- 10950576
TI  - An editorial reply to the pecking order of new patients.

PMID- 10950577
TI  - In my hands...

PMID- 10950578
TI  - Regarding the pecking order of new patients.

PMID- 10950579
TI  - Unnecessary destruction of the skin overlying dermal lesions.

PMID- 10950580
TI  - 50% TCA, scarring, scarring, and shared risks of resurfacing procedures.

PMID- 10950581
TI  - Surgical treatment of vitiligo.

PMID- 10950582
TI  - Mohs micrographic surgery.

PMID- 10950583
TI  - Clinical trial size and efficacy.

PMID- 10950584
TI  - Regarding function in the long saphenous vein.

PMID- 10950585
TI  - Photographic comparison as evidence of therapeutic success in aesthetic
      dermatosurgery.

PMID- 10950586
TI  - Regarding malpractice claims.

PMID- 10950588
TI  - Response to commentary on modified tumescent liposuction.

PMID- 10950587
TI  - George Popkin--tribute.

PMID- 10950589
TI  - Regarding the use of contact cooling devices during laser treatment of spider leg
      veins.

PMID- 10950590
TI  - Regarding disappointing results.

PMID- 10950591
TI  - Recommended epinephrine concentration with local anesthetic.

PMID- 10950592
TI  - Regarding financial interest.

PMID- 10950593
TI  - Regarding the pathophysiology of venous ulcers.

PMID- 10950594
TI  - Regarding combined therapy for neck rejuvenation.

PMID- 10950595
TI  - Regarding the facial flap.

PMID- 10950596
TI  - Pig head model for practice cutaneous surgery.

PMID- 10950597
TI  - Scalp cyanosis during hair transplantation.

PMID- 10950598
TI  - Regarding CO2 laser resurfacing infection rates.

PMID- 10950599
TI  - Recurrent varices after surgery (REVAS), a consensus document. REVAS group.

PMID- 10950600
TI  - Importation of diseases following the relaxation of quarantine regulations.

PMID- 10950601
TI  - Brain-Gut 2000. 3-5 July 2000, Toulouse, France. Abstracts.

PMID- 10950602
TI  - [Surgical treatment of inguinal hernia in middle-aged and elderly patients].

PMID- 10950603
TI  - Programmed cell-death regulation: basic mechanisms and therapeutic opportunities.
      American Association for Cancer Research Special Conference: Lake Tahoe, CA, USA,
      27 February-2 March 2000.

PMID- 10950604
TI  - My choice: History repeats itself. The prevention of syringe transmitted
      hepatitis.

PMID- 10950605
TI  - My choice: Cortisone in the treatment of syphilitic eye disease.

PMID- 10950606
TI  - My choice: Chlamydia trachomatis in STDs: early days of the modern era.

PMID- 10950607
TI  - My choice: Medical professional secrecy with special reference to venereal
      diseases.

PMID- 10950608
TI  - My choice: Natural history of genital warts.

PMID- 10950609
TI  - My choice: Now on stage--chlamydia.

PMID- 10950610
TI  - My choice: 27 years of uninterrupted contact tracing: the "Tyneside scheme".

PMID- 10950611
TI  - My choice: Memorable Chlamydia trachomatis papers.

PMID- 10950612
TI  - My choice: The life and times of Colonel L W Harrison. The first Harrison
      Lecture.

PMID- 10950613
TI  - My choice: The shift of paradigm or "the chlamydial bandwagon".

PMID- 10950614
TI  - My choice: Survival of treponemes after treatment: comments, clinical conclusions
      and recommendations.

PMID- 10950615
TI  - My choice: Sexual behaviour in women attending a genitourinary medicine clinic.

PMID- 10950616
TI  - My choice: Teenagers and the risks of sexually transmitted diseases: a need for
      the provision of balanced information.

PMID- 10950617
TI  - My choice: Infectivity tests in syphilis.

PMID- 10950618
TI  - Promotion of professional portfolios.

PMID- 10950619
TI  - Strabology report of the 26th annual meeting of the American Association for
      Pediatric Ophthalmology and Strabismus.

PMID- 10950620
TI  - Report of the 15th annual Cullen course, Pediatric Ophthalmology [and Strabismus]
      Section Baylor College of Medicine, Houston, Texas, March 3-5, 2000.

PMID- 10950621
TI  - Economic aspects of haemophilia care in the United States.

PMID- 10950622
TI  - Second Workshop of the European Paediatric Network for Haemophilia Management, 17
      19 September 1998 in Vitznau/Switzerland.

PMID- 10950624
TI  - Patenting life's instructions.

PMID- 10950623
TI  - Gene for familial primary pulmonary hypertension identified.

PMID- 10950625
TI  - [Intrauterine device and infertility: have the risks changed? Can an intrauterine
      device be used in a nulliparous woman?].

PMID- 10950626
TI  - Perspectives on the development of new antimicrobial agents for resistant gram
      positive pathogens.
AB  - There is great public and professional concern related to antimicrobial
      resistance, especially among Gram-positive pathogens associated with high
      morbidity and mortality. Penicillin-nonsusceptible Streptococcus pneumoniae,
      glycopeptide resistant enterococci, and oxacillin-resistant (MRSA) or vancomycin
      intermediate (VISA) Staphylococcus aureus isolates continue to escalate in
      occurrence leading to the widespread use of empiric combination regimens. Newer,
      often novel, agents seem necessary to combat these pathogens. Among these,
      quinupristin/dalfopristin (Synercid), evernimicin or SCH 27899 (Ziracin), and
      linezolid (Zyvax) have the highest potency, widest spectrum, and most clinical
      experience. Among the quinolones (gatifloxacin, gemifloxacin, moxifloxacin),
      gatifloxacin is closest to clinical use and appears safe based on initial trial
      reports. Several broad-spectrum beta-lactams ("fourth-generation" cephalosporins,
      carbapenems) are expected to be used with increasing frequency as a result of the
      emerging high rates of specific beta-lactamases that compromise the use of
      ceftriaxone, ceftazidime, and many beta-lactamase inhibition/ penicillin
      combinations. Among these agents, cefepime and meropenem are the most potent and
      broadest in clinical application in their respective classes. Physicians must
      stay informed about drug development and antimicrobial resistance by using
      results from local surveillance programs. When these data are unavailable,
      physicians should consider the use of national or global monitoring systems
      (SENTRY) to direct empiric antimicrobial selection.

PMID- 10950628
TI  - Into the next millennium.

PMID- 10950627
TI  - Problems and perils of vancomycin resistant enterococci.
AB  - Enterococci have been a therapeutic challenge for haIfa century; first in the
      management of endocarditis, then associated with the emergence of resistance to
      streptomycin and later to all aminoglycosides, and now with the increasing levels
      of resistance to penicillins. A major leap in the problem of antimicrobial
      resistance occurred more than a decade ago when vancomycin resistant enterococci
      (VRE) were first identified. This resulted from the acquisition by Enterococcus
      faecium of vancomycin resistant genes. Five types of vancomycin resistance have
      since been described (VanA-VanE) and others also appear to exist. VanA and VanB
      are caused by complex gene clusters that may be plasmid and/or transposon
      encoded. As a result of the gene cluster, cell wall precursors in the bacteria
      are formed that do not allow effective vancomycin binding, thus the action of
      vancomycin to inhibit cell wall synthesis is prevented. Therapy of infections
      caused by VRE is difficult, but a number of potentially effective antibiotics are
      now being tested in humans, including quinupristin/dalfopristin, linezolid,
      evernimomycin, daptomycin and LY333328. Combinations of antibiotics such as
      ampicillin with quinupristin/dalfopristin or with imipenem, and newer
      fluoroquinolones are also being evaluated. Until the time when these drugs become
      available, we must rely on careful monitoring of microbial transmission in
      hospitals, and we must utilize multi-faceted approaches to prevent the increase
      in the number and spread of VRE.

PMID- 10950629
TI  - Transplantation in Japan: the crusade begins.

PMID- 10950630
TI  - Can rodent cancer tests predict for human cancers? Proceedings of a toxicology
      symposium. Little Rock, Arkansas, USA. November 12-13, 1998.

PMID- 10950631
TI  - [Chromosome 21 deciphered. An impetus to research on Down syndrome?].

PMID- 10950632
TI  - [Mediterranean spotted fever].

PMID- 10950633
TI  - [The blood pressure-lowering effect of garlic].

PMID- 10950634
TI  - From metmyoglobin to deoxy myoglobin: relaxations of an intermediate state.
AB  - Metmyoglobin has been reduced at low temperature (below 100 K) using x-rays or by
      excitation of tris(2,2,bipyridine)ruthenium(II) chloride with visible light. Upon
      reduction, an intermediate state is formed where the structure of the protein is
      very similar to that of metmyoglobin with the water molecule still bound to the
      heme iron, but the iron is II low spin. The nature of the intermediate state has
      been investigated with optical spectroscopy. The Q(O) and Q(V) bands of the
      intermediate state are split, suggesting that the protoporphyrin is distorted.
      The intermediate state undergoes a relaxation observed by a shifting of the Soret
      band at temperatures above 80 K. Above 140 K, the protein begins to relax to the
      deoxy conformation. The relaxation kinetics of the protein have been monitored
      optically as a function of time and temperature from minutes to several hours and
      from 150 K to 190 K. By measuring the entire visible spectrum, we are able to
      distinguish between electron transfer processes and the protein relaxation from
      the intermediate state to deoxy myoglobin. The relaxation has been measured in
      both horse myoglobin and sperm whale myoglobin with the relaxation occurring on
      faster time scales in horse myoglobin. Both the reduction kinetics and the
      relaxation show non-exponential behavior. The reduction kinetics can be fit well
      to a stretched exponential. The structural relaxation from the intermediate state
      to the deoxy conformation shows a more complex, dynamical behavior and the
      reaction is most likely affected by the relaxation of the protein within the
      intermediate state.

PMID- 10950635
TI  - Triple helix DNA oligomer melting measured by fluorescence polarization
      anisotropy.
AB  - A synthetic DNA triple helix sequence was formed by annealing a pyrimidinic 21
      mer single strand sequence onto the complementary purinic sequence centred on a
      27 mer duplex DNA. Melting of the third strand was monitored by UV
      spectrophotometry in the temperature range 10-90 degrees C. The T(m) of the
      triplex, 37 degrees C, was well separated from the onset of duplex melting. When
      the same triple helix was formed on the duplex bearing one nick in the center of
      the pyrimidinic sequence the T(m) of the triplex was shifted to approximately 32
      degrees C and overlapped the melting of the duplex. We have used fluorescence
      polarization anisotropy (FPA) measurements of ethidium bromide (EB) intercalated
      in duplex and triplex samples to determine the hydrodynamic parameters in the
      temperature range 10-40 degrees C. The fluorescence lifetime of EB in the samples
      of double and triple stranded DNA is the same (21.3 +/- 0.5 ns) at 20 degrees C,
      indicating that the geometries of the intercalation sites are similar. The values
      for the hydration radii of the duplex, normal triplex, and nicked triplex samples
      were 10.7 +/- 0.2, 12.2 +/- 0.2, and 12.0 +/- 0.2 A. FPA measurements on normal
      triplex DNA as a function of temperature gave a melting profile very similar to
      that derived by UV absorption spectroscopy. For the triplex carrying a nick, the
      melting curve obtained using FPA showed a clear shift compared with that obtained
      for the normal triplex sample. The torsional rigidity of the triplex forms was
      found to be higher than that of the duplex form.

PMID- 10950636
TI  - Interaction of methyl green with an oligonucleotide in intramolecular duplex and
      triplex conformations. Circular dichroism studies.
AB  - Interaction of methyl green with the oligonucleotide 5-dGGAAAAGG-[T4]-GGAAAAGG
      [T4]-CCTTTTCC (where [T4] is a nucleotide sequence of four thymines) in hairpin
      duplex and in intramolecular triplex structures has been studied by circular
      dichroism. We found that methyl green binding to the duplex form shows a complex
      pattern, exhibiting an exciton contribution when the number of bound molecules
      increases. Differences between this pattern and previously published results on
      other DNAs reveals the presence of different types of complexes. In contrast to
      previous findings with the triple helix poly(dA).2poly(dT) we show that the
      methyl green is not toallly excluded from this triplex structure made of
      Pur:Pur:Pyr triplets.

PMID- 10950637
TI  - Molecular dynamics investigations of hammerhead ribozyme RNA.
AB  - The hammerhead ribozyme, a small catalytic RNA molecule, cleaves, in the presence
      of magnesium ions, a specific phosphodiester bond within its own backbone,
      leading to 23-cyclic phosphate and 5-OH extremities. In order to study the
      dynamical flexibility of the hammerhead RNA, we performed molecular dynamics
      simulations of the solvated crystal structure of an active hammerhead ribozyme,
      obtained after flash-freezing crystals soaked with magnesium. Because of a
      careful equilibration protocol and the use of the Ewald summation in calculating
      the electrostatic interactions, the RNA structure remained close to the crystal
      structure, as attested by a root-mean-square deviation below 2.5 A after 750 ps
      of simulation. All Watson-Crick base pairs were intact at the end of the
      simulations. The tertiary interactions, such as the sheared G.A pairs and the U
      turn, important for the stabilisation of the three-dimensional RNA fold, were
      also retained. The results demonstrate that molecular dynamics simulations can be
      successfully used to investigate the dynamical behaviour of a ribozyme, thus,
      opening a road to study the role of transient structural changes involved in
      ribozyme catalysis.

PMID- 10950638
TI  - Study of amide proton exchange in 15N-enriched cryptogein using pH-dependent off
      resonance ROESY-HSQC experiments.
AB  - A new pH-dependent off-resonance ROESY-HSQC experiment has been used to
      characterize the degree of protection of the amide protons of cryptogein, a
      protein of the elicitin family, against solvent exchange. The study of the pH
      dependence of solvent-shielded amide protons in this protein reveals that the
      helices have different levels of stability. Two of the five helices exhibit
      strong protection of amide hydrogens against exchange with the solvent. By
      contrast, greater flexibility is observed in the other three helices,
      particularly in the C-terminal helix. These results provide information on the
      dynamic features of the protein and are consistent with the RMSD for the backbone
      atoms of residues involved in helical structures. In addition, the question of
      the flexibility in a hydrophobic cavity made of conserved residues, which
      represent a plausible binding site, is addressed by this method.

PMID- 10950639
TI  - A reduction of protein specific motions in co-ligated myoglobin embedded in a
      trehalose glass.

PMID- 10950640
TI  - Heteroduplex rejection in yeast?

PMID- 10950641
TI  - Using the false discovery rate approach in the genetic dissection of complex
      traits: a response to Weller et al.

PMID- 10950642
TI  - Cord blood lymphocytes have a low frequency of cytokine producing T cells due to
      a high threshold for activation.

PMID- 10950643
TI  - [Hospitals under pressure for accommodation].

PMID- 10950644
TI  - [Effects of DRGs on the hospital budget].

PMID- 10950645
TI  - [Euthanasia in the Netherlands out of control; critical review by a Dutch
      physician].

PMID- 10950646
TI  - A comment on proliferation rates in human prostate cancer.

PMID- 10950647
TI  - Regarding Mohan, Kuplian, and Willoughby, IJROBP 2000;46:575-580.

PMID- 10950648
TI  - Regarding Giap and Massullo, IJROBP 1999;45:1355-1358.

PMID- 10950649
TI  - Re: nodal evaluation in breast cancer.

PMID- 10950650
TI  - Regarding D'Amico et al., IJROBP 1999;45:1227-1233.

PMID- 10950652
TI  - Diagnosis of traumatic lens dislocations.

PMID- 10950653
TI  - Tetanus not 100% preventable.

PMID- 10950654
TI  - The potential etiologic role of Chlamydia pneumoniae in atherosclerosis.
      Proceedings of a meeting. Seattle, Washington, USA. 22-25 September 1999.

PMID- 10950655
TI  - [Temporomandibular joint disorders].

PMID- 10950656
TI  - Surveillance after colorectal cancer resection.

PMID- 10950657
TI  - From the Centers for Disease Control and Prevention. Use of medical care, police
      assistance, and restraining orders by women reporting intimate partner violence-
      Massachusetts, 1996-1997.

PMID- 10950658
TI  - From the Centers for Disease Control and Prevention. Prevalence of intimate
      partner violence and injuries--Washington, 1998.

PMID- 10950659
TI  - JAMA patient page. Helping children cope with violence.

PMID- 10950660
TI  - From the Food and Drug Administration.

PMID- 10950661
TI  - From the Centers for Disease Control and Prevention. Delayed supply of influenza
      vaccine and adjunct ACIP influenza vaccine recommendations for the 2000-01
      influenza season. Advisory Committee on Immunization Practices.

PMID- 10950663
TI  - From the Centers for Disease Control and Prevention. National, state and urban
      area vaccination coverage levels among children aged 19-35 months--United States,
      1999.

PMID- 10950664
TI  - JAMA patient page. Preventing tobacco use in children and adolescents.

PMID- 10950662
TI  - From the Centers for Disease Control and Prevention. Outbreak of gastroenteritis
      associated with an interactive water fountain at a beachside park--Florida, 1999.

PMID- 10950665
TI  - Working from the particular to the general--the development of comparative
      genomics--a meeting report from the 4th Annual Conference on Microbial Genomes.

PMID- 10950666
TI  - [Efficient prevention of relapse with acamprosate].

PMID- 10950667
TI  - High plasma levels of factor VIII and the risk of recurrent venous
      thromboembolism.
AB  - BACKGROUND: A high plasma level of factor VIII is a risk factor for venous
      thromboembolism. We evaluated the risk of a recurrence of thrombosis after an
      initial episode of spontaneous venous thromboembolism among patients with high
      plasma levels of factor VIII. METHODS: We studied 360 patients for an average
      follow-up period of 30 months after a first episode of venous thromboembolism and
      discontinuation of oral anticoagulants. Patients who had recurrent or secondary
      venous thromboembolism, a congenital deficiency of an anticoagulant, the lupus
      anticoagulant, hyperhomocysteinemia, cancer, or a requirement for long-term
      treatment with antithrombotic drugs or who were pregnant were excluded. The end
      point was objectively documented, symptomatic recurrent venous thromboembolism.
      RESULTS: Recurrent venous thromboembolism developed in 38 of the 360 patients
      (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of
      factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per
      deciliter, P=0.009). The relative risk of recurrent venous thrombosis was 1.08
      (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10
      IU per deciliter in the plasma level of factor VIII. Among patients with a factor
      VIII level above the 90th percentile of the values in the study population, the
      likelihood of recurrence at two years was 37 percent, as compared with a 5
      percent likelihood among patients with lower levels (P<0.001). Among patients
      with plasma factor VIII levels above the 90th percentile, as compared with those
      with lower levels, the overall relative risk of recurrence was 6.7 (95 percent
      confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or
      absence of factor V Leiden or the G20210A prothrombin mutation, and the duration
      of oral anticoagulation. CONCLUSIONS: Patients with a high plasma level of factor
      VIII have an increased risk of recurrent venous thromboembolism.

PMID- 10950669
TI  - Is academic medicine for sale?

PMID- 10950668
TI  - Successful hand transplantation. One-year follow-up. Louisville Hand Transplant
      Team.
AB  - BACKGROUND: On the basis of positive results in studies of the transplantation of
      pig extremities and the information exchanged at an international symposium on
      composite tissue transplantation, we developed a protocol for human hand
      transplantation. METHODS: After a comprehensive pretransplantation evaluation and
      informed-consent process, the left hand of a 58-year-old cadaveric donor, matched
      for size, sex, and skin tone, was transplanted to a 37-year-old man who had lost
      his dominant left hand 13 years earlier. Immunosuppression consisted of
      basiliximab for induction therapy and tacrolimus, mycophenolate mofetil, and
      prednisone for maintenance therapy. RESULTS: The cold-ischemia time of the donor
      hand was 310 minutes. There were no intraoperative or early postoperative
      complications. Moderate acute cellular rejection of the skin of the graft
      developed 6, 20, and 27 weeks after transplantation. All three episodes resolved
      completely after treatment with intravenous methylprednisolone and topical
      tacrolimus and clobetasol. Temperature, pain, and pressure sensation had
      developed in the hand and fingers by one year. At one year, the patient had
      regained the ability to perform many functional activities with his left hand
      that he had not been able to perform with his prosthesis, such as throwing a
      baseball, turning the pages of a newspaper, writing, and tying his shoelaces.
      CONCLUSIONS: Early success has been achieved in hand transplantation with the use
      of currently available immunosuppressive drugs.

PMID- 10950670
TI  - Is academic medicine for sale?

PMID- 10950671
TI  - Is academic medicine for sale?

PMID- 10950672
TI  - Is academic medicine for sale?

PMID- 10950673
TI  - Is academic medicine for sale?

PMID- 10950674
TI  - Is academic medicine for sale?

PMID- 10950675
TI  - Clinical investigators and the pharmaceutical industry.

PMID- 10950676
TI  - Clinical investigators and the pharmaceutical industry.

PMID- 10950677
TI  - Chest pain and normal coronary arteries.

PMID- 10950678
TI  - C-reactive protein in the prediction of cardiovascular disease.

PMID- 10950679
TI  - Bradycardia.

PMID- 10950680
TI  - Review of Marihuana and Medicine.

PMID- 10950681
TI  - Use of heparin during cardiopulmonary bypass in patients with a history of
      heparin-induced thrombocytopenia.

PMID- 10950682
TI  - [Tumors of the third ventricle. Proceedings of the 50th Annual Congress of the
      French Language Society of Neurosurgery. Reims, France, 4-7 June 2000].

PMID- 10950683
TI  - Intermittent claudication treatment.

PMID- 10950684
TI  - Guide to nursing organizations 2000.

PMID- 10950685
TI  - Otitis Media Forum. Proceedings of a symposium. Carmel, California, USA.
      September 23-25, 1999.

PMID- 10950686
TI  - Prediction of tumor response to therapy: molecular markers and the
      microenvironment. Apoptosis and chips: an overview of the proceedings.

PMID- 10950687
TI  - Paternal irradiation and leukemia in offspring.

PMID- 10950688
TI  - Non-equilibrium and coherent systems in biology, biophysics and biotechnology.
      2nd International Alexander Gurwitsch Conference. Moscow, Russia, September 6-10,
      1999. Abstracts.

PMID- 10950689
TI  - Resolving conflicts between drinking water demands and pressures from society's
      wastes. Proceedings of an International Conference. Bad Elster, Germany, 24-28
      November 1998.

PMID- 10950691
TI  - [Solidarity! Solidarity?].

PMID- 10950690
TI  - Resolving conflicts between drinking-water demands and pressures from society's
      wastes.

PMID- 10950692
TI  - [Study reform in dentistry].

PMID- 10950693
TI  - [The prevalence of acute necrotizing ulcerative gingivitis in Swiss military
      collectives].
AB  - A group of 1595 military trainees (age range 18 to 30) were screened for the
      appearance of acute necrotizing ulcerative gingivitis. In a second phase four
      military dentists examined over 2800 newly entered trainees. Criteria for the
      diagnosis of ANUG were (1) Ulceration and necrosis of the interdental papilla,
      (2) bleeding and (3) pain. Among the 1595 recruits no ANUG could be detected, and
      no case of ANUG was reported by the four military-dentists. Thus, the prevalence
      of acute necrotizing ulcerative gingivitis was calculated to be below 0.03%.

PMID- 10950695
TI  - [The side effects due to vaccination against hepatitis B. Issued by the Federal
      Office of Public Health, the Association of Cantonal Physicians and the Swiss
      Commission for Vaccinations].

PMID- 10950694
TI  - [Restorative dentistry 2000, Prof. Dr. Scharer, MS, 12-18 March 2000 in St.
      Moritz. The continuing education week by Prof. Dr. Scharer, MS, in St. Moritz].

PMID- 10950697
TI  - [Have I really accomplished the objectives I set myself?].

PMID- 10950696
TI  - [A summary of maxillomandibular reparative surgery. A report on the 41st Annual
      Meeting of the Swiss Association for Oral Surgery and Mouth Diseases (SAKM), 1
      April 2000 in Geneva].

PMID- 10950699
TI  - [I want a crown, a bleaching ...].

PMID- 10950698
TI  - [The For the Milk Tooth action at the GESUND 2000 health exhibit].

PMID- 10950700
TI  - [Necrotizing ulcerative gingivitis: its prevalence in Swiss military
      collectives].

PMID- 10950701
TI  - [The side effects related to hepatitis B inoculation. Issued by the Federal
      Office of Public Health, Association of Cantonal Physicians and the Swiss
      Commission for Vaccinations].

PMID- 10950702
TI  - [The immediate-immediate implant--state of the art. A report on the congress of 6
      7 May 2000 in Zurich (the University of Zurich, Clinic for Crown and Bridge
      Dentures, Partial Dentures and Dental Materials Science. Director: Prof. Dr. P.
      Scharer, M.S.)].

PMID- 10950703
TI  - [Periodontology--an update for daily practice].

PMID- 10950704
TI  - [Communication in the dentist's practice--the risky trick in everyday life].

PMID- 10950705
TI  - [Telephone book entry].

PMID- 10950706
TI  - [The importance and consequence of correct and consistent hygiene and
      ergonomics].

PMID- 10950707
TI  - Clinical research. Flawed cancer study leads to shake-up at University of
      Oklahoma.
AB  - Allegations of lax safety procedures and flawed management in a clinical cancer
      trial have cost four researchers and administrators their jobs at the University
      of Oklahoma. They have also led to a temporary shutdown of 75 clinical trials at
      the university's Health Science Center in Tulsa and a sweeping overhaul of the
      school's process for approving human experiments. University officials emphasize
      that none of the roughly 100 patients involved in the 3-year-old study of an
      experimental cancer vaccine was known to have been harmed, and that most trials
      will soon be restarted.

PMID- 10950708
TI  - NASA life sciences. An improvement in vital signs.
AB  - Last week a hefty Russian module with living and working quarters for astronauts
      docked with the pieces of the international space station already in orbit, a
      critical step in creating a full-time orbiting laboratory. Meanwhile, NASA
      bureaucrats put the finishing touches on a realignment of the agency's struggling
      biology effort that should bolster fundamental research and allow scientists to
      make better use of the facility, scheduled to be completed in 2005. The two
      events raise the hopes of U.S. academic space life scientists that their
      discipline is at last on the ascent at NASA.

PMID- 10950709
TI  - Biotechnology. USDA to commercialize 'terminator' technology.

PMID- 10950710
TI  - Air pollution. Panel backs EPA and 'six cities' study.
AB  - The Environmental Protection Agency (EPA) has won a major victory in the fierce
      battle over its tough new standard for particulate air pollution. Dealing a sharp
      blow to critics from industry, a nonpartisan research group has reevaluated key
      data that EPA relied upon to set that standard and has come out firmly behind the
      agency.

PMID- 10950711
TI  - A wetter, younger Mars emerging.
AB  - Most researchers have believed that the days were long gone when water splashed
      on the surface of Mars or even near it. Now continuing analyses of martian
      meteorites and stunning images from the Mars Global Surveyor (MGS), which has
      been in orbit since 1997, are breathing new life into the Red Planet. Last
      month's announcement that the camera aboard MGS had spied signs of geologically
      recent--possibly even ongoing--water seeps has caught everyone's attention.
      Other, perhaps more persuasive, signs also suggest that water may even now flow
      on or beneath the frigid surface.

PMID- 10950712
TI  - Ecology. Can science rescue salmon?
AB  - At a press conference on 27 July, the National Marine Fisheries Service (NMFS)
      released a long-awaited plan to save the Columbia River's endangered salmon by
      restoring fish habitat, overhauling hatcheries, limiting harvest, and improving
      river flow. What the plan did not do, however, was call for immediate breaching
      of four dams on the Snake River, the Columbia's major tributary--an option that
      has been the subject of a nationwide environmental crusade. The NMFS will hold
      that option in abeyance while it sees whether the less drastic measures will do
      the trick. Responses from both sides were immediate and outraged.

PMID- 10950713
TI  - Epidemiology. Duke study faults overuse of stimulants for children.
AB  - Some experts are growing concerned that Ritalin, a stimulant of the central
      nervous system used to calm a type of fidgety behavior called "attention-deficit
      hyperactivity disorder" (ADHD), is overused. Most psychiatrists think, however,
      that stimulants are being underprescribed, because too many cases of ADHD are
      going untreated. Now, an authoritative study published in this month's Journal of
      the American Academy of Child and Adolescent Psychiatry shows that Ritalin is
      being given to many children who don't fit the diagnosis of ADHD, while others
      who do are not receiving the drug.

PMID- 10950714
TI  - Preservation of DNA from endangered species.

PMID- 10950715
TI  - Preservation of DNA from endangered species.

PMID- 10950716
TI  - Cell biology. Bacterial spelunkers.
AB  - Bacteria that are engulfed by phagocytic cells of the immune system are usually
      destroyed once inside the host cell but not always. Why is it that sometimes
      engulfed bacteria survive and thrive quite happily inside the host cell? As
      Mulvey and Hultgren explain in their Perspective, the answer may lie in small
      indentations in the host cell plasma membrane called caveolae that direct certain
      signal transduction pathways inside the host cell (Shin et al.). If bacteria
      adhere to regions of the host cell surface that is rich in caveolae, they are
      better able to survive once inside the cell.

PMID- 10950717
TI  - Structure. Rhodopsin sees the light.
AB  - Members of the seven transmembrane receptor superfamily bind a remarkable variety
      of ligands, from neurotransmitters to odorants, and activate a spectacular array
      of G protein signaling molecules. These G-protein coupled receptors (GPCRs) are
      important in many cellular functions and so there has been great interest in
      elucidating how they transmit their signals to the interior of the cell after
      activation by ligand. As Bourne and Meng explain in their Perspective, the
      molecular movements of activated GPCRs are becoming clear now that the first
      crystal structure of a GPCR (rhodopsin, the light-trapping receptor found in the
      retina of the eye) has been reported (Palczweski et al.).

PMID- 10950718
TI  - Cell cycle. Replication meets cohesion. .
AB  - When a cell replicates its DNA during S phase of the cell cycle, the sister
      chromatid pairs must stick together like glue until they are separated to
      opposite ends of the cell (and hence into separate daughter cells) at anaphase.
      How the cell achieves this is still unclear but, as Takahashi and Yanagida
      explain in their Perspective, new findings in yeast have identified one molecule,
      Trf4p, that may be involved both in DNA replication and sister chromatid cohesion
      (Wang et al.).

PMID- 10950719
TI  - Biomineralization. Naturally aligned nanocrystals.
AB  - The aggregation of nanocrystals has long been believed to result in disordered
      solids. In his Perspective, Alivisatos discusses recent evidence that
      nanocrystals may also form oriented assemblies. He highlights the work by
      Banfield et al. in this issue, who show that such alignment can also occur in
      natural systems. The results may be of importance not only for geochemistry but
      also for the synthesis of advanced artificial materials.

PMID- 10950720
TI  - "Opportunist" mycobacterial infections.

PMID- 10950721
TI  - Antibiotic prescribing in the community.

PMID- 10950722
TI  - Genetic susceptibility to COPD.

PMID- 10950723
TI  - Genetic susceptibility to COPD.

PMID- 10950724
TI  - Fluticasone in asthma.

PMID- 10950725
TI  - [Classic fowl plague or avian influenza].

PMID- 10950726
TI  - [The worthwhile visit: Museum of Cattle Breeding in KI. The world-famous Dutch
      breeding in focus].

PMID- 10950727
TI  - [Food inspection of merchandise. Change in destruction law: dead dogs and cats
      are now specified high risk material].

PMID- 10950728
TI  - [Repeated notice. Unpredictable aggression by golden retrievers: a hereditary
      problem?].

PMID- 10950729
TI  - [The discovery of the Lelystad virus. A high point in Dutch veterinary research
      during the last ten years (1990-1999)].

PMID- 10950730
TI  - [Uncontrolled wart-like growth on the ears of rats].

PMID- 10950731
TI  - [Conclusion of BVD approach].

PMID- 10950732
TI  - [Problems with respiratory disorders on farms].

PMID- 10950733
TI  - [The Veterinary Disciplinary Board. Unauthorized availability of UDA veterinary
      drugs].

PMID- 10950734
TI  - [The role of Dutch veterinarians in the drug residue problem].

PMID- 10950736
TI  - [Dissertations defended at the end of 1999].

PMID- 10950735
TI  - The subgenus Leishmania (Leishmania): a citation correction.

PMID- 10950737
TI  - [Dissertations defended in 1999].

PMID- 10950738
TI  - [The 110th anniversary of the birth of I. Ia. Razdol'skii].

PMID- 10950739
TI  - Belgian Association for Study of Cancer. Ghent, January 29, 2000. Abstracts.

PMID- 10950740
TI  - P terminal force in lead V (1).

PMID- 10950741
TI  - Our ancestors had it right.

PMID- 10950742
TI  - Nursing rounds at University of Pennsylvania. Crisis in recovery.

PMID- 10950743
TI  - [Euthanasia--assisted suicide].

PMID- 10950744
TI  - [Postoperative delirium following vascular surgery. Comparative results in a
      prospective study].

PMID- 10950746
TI  - Colorectal Cancer: New Aspects of Molecular Biology, Immunology and Clinical
      Applications. Proceedings of a conference. Berlin, Germany, October 8-9, 1999.

PMID- 10950745
TI  - Vitamin D.

PMID- 10950747
TI  - Stamps in paediatrics. Child help-lines.

PMID- 10950749
TI  - Which children should receive growth hormone treatment. Long term side effects
      possible with high doses.

PMID- 10950748
TI  - Which children should receive growth hormone treatment. Cost-benefit analysis is
      the key.

PMID- 10950750
TI  - Cefadroxil in hyperimmunoglobulin E syndrome.

PMID- 10950751
TI  - Cystic fibrosis mutations and disease phenotype.

PMID- 10950752
TI  - Lack of involvement of the Fas system in ankylosing spondylitis.

PMID- 10950753
TI  - HLA-DRB1*04 may be a marker of severity in giant cell arteritis.

PMID- 10950754
TI  - Acute oedematous dermatomyositis.

PMID- 10950755
TI  - Cytomegalovirus infection decreases expression of thrombospondin-1 and -2 in
      cultured human retinal glial cells: effects of antiviral agents.
AB  - In fibroblasts, infection with human cytomegalovirus (HCMV) inhibits expression
      of the extracellular matrix proteins thrombospondin-1 and -2 (TSP-1 and TSP-2).
      These effects may depend on expression of HCMV immediate-early (IE) genes, which
      are activated by cellular transcription factor NF-kappaB. The influence of HCMV
      infection on TSP-1 and TSP-2 expression and the ability of different antiviral
      drugs to prevent these cellular changes in permissive cultures of human retinal
      glial cells were observed. Ganciclovir inhibited only HCMV late antigen (LA)
      expression, whereas antisense oligonucleotide ISIS 2922 and peptide SN50,
      inhibitors of HCMV IE expression and NF-kappaB activity, respectively, inhibited
      both IE and LA expression. ISIS 2922 and SN50, but not ganciclovir, prevented
      down-modulation of TSP-1 and TSP-2. The results showed that HCMV-induced down
      modulation of TSP-1 and TSP-2 in retinal glial cells is prevented by inhibition
      of HCMV IE expression. These findings may be relevant to pathogenesis and
      treatment of HCMV retinitis.

PMID- 10950756
TI  - Immune transfer protects severely immunosuppressed mice from murine
      cytomegalovirus retinitis and reduces the viral load in ocular tissue.
AB  - Cytomegalovirus (CMV) retinitis is a sight-threatening disease that affects
      immunosuppressed people and is prevalent in people with AIDS. The purpose of this
      study was to evaluate murine CMV (MCMV) retinitis in a replenishing model with
      adoptive immune transfer into severely immunosuppressed animals. Adult BALB/c
      mice, immunosuppressed with cyclophosphamide, were infected subretinally with
      5x102 plaque-forming units of MCMV. Four to six hours later, 3-4x107 donor cells
      were transferred by intravenous infusion. Eight days after the transfer, the eyes
      that had received donor cells were studied histologically, titered for infectious
      virus, and analyzed with polymerase chain reaction (PCR). Adoptive transfer of
      total MCMV-immune lymph node (LN) cells or enriched LN lymphocytes specifically
      and significantly protected immunosuppressed mice from retinitis even after the
      initiation of infection. The transfer resulted in a reduced viral load, as
      measured by both plaque assay and PCR. This replenishment model will be useful
      for determining the specific immune parameters of protection from CMV retinitis.

PMID- 10950757
TI  - Antigen-specific T cells localize to the uterine cervix in women with genital
      herpes simplex virus type 2 infection.
AB  - Genital reinfection with herpes simplex virus type 2 (HSV-2) is uncommon in
      humans. The mechanism of acquired immunity is unknown. Because the cervix is a
      site of HSV exposure, we measured antigen-specific T cell responses to HSV in
      cervical lymphocytes during both lesional and nonlesional time periods. Cells
      were expanded without secondary in vitro stimulation with antigen. Proliferative
      and cytotoxic responses to HSV were detectable in specimens from most subjects.
      Limiting dilution assays showed a high frequency of antigen-specific cells.
      Cytotoxic T cell responses included both CD4 and CD8 components. Responses were
      present both during and between symptomatic infection episodes and persisted
      during suppressive antiviral therapy. Natural infection with HSV-2 is associated
      with a persistent cervical mucosal cellular immune response. This local response
      may possibly assist in limiting the clinical consequences of secondary HSV-2
      infection, whether due to endogenous reactivation or exogenous reinfection.

PMID- 10950758
TI  - Respiratory syncytial virus (RSV)-induced airway hyperresponsiveness in
      allergically sensitized mice is inhibited by live RSV and exacerbated by formalin
      inactivated RSV.
AB  - Respiratory syncytial virus (RSV)-induced disease is associated with recurrent
      episodes of wheezing in children, and an effective vaccine currently is not
      available. The use of 2 immunizations (a formalin-inactivated, alum-precipitated
      RSV vaccine [FI-RSV] given intramuscularly and live RSV given intranasally
      [LVIN]), with a control immunization, were compared in a well-characterized model
      of RSV challenge, with or without concomitant allergic sensitization with
      ovalbumin. FI-RSV caused a significant increase in airway hyperresponsiveness in
      mice after RSV infection during allergic sensitization, and this was associated
      with an increase in type 2 cytokine production. In contrast, immunization with
      LVIN did not change type 2 cytokine production and protected against RSV-induced
      airway hyperresponsiveness in the setting of allergic sensitization. This study
      suggests that immune modulation with RSV vaccination can have profound effects on
      RSV-induced airway disease and that prevention of airway hyperresponsiveness is
      an important end point in vaccine development.

PMID- 10950759
TI  - Incidence and genetic diversity of group C rotavirus among adults.
AB  - Fecal samples from a 1-year prospective study were investigated to establish the
      role of group C rotavirus infections in acute diarrhea in Swedish adults (>15
      years old). Rotaviruses were found in samples from 3% of the patients, and, in
      35% of these, group C rotavirus was detected. Clinical symptoms of group C
      rotavirus infection were generally milder than those of group A rotavirus
      infection. Gene 8 (vp7) from 12 group C isolates, including strains from the
      prospective study, a military outbreak, and a sporadic case, was sequenced. The
      gene was found to be extremely conserved, with identities of 99.1%-100% at the
      amino acid level. This study has systematically investigated the prevalence and
      genetic diversity of group C rotavirus in adults. The data confirm the extreme
      sequence conservation within human group C rotavirus strains and suggest that
      symptomatic group C rotavirus infections occur more frequently in adults than has
      been previously recognized.

PMID- 10950760
TI  - Astrovirus diarrhea in Egyptian children.
AB  - This study describes the epidemiology of astrovirus diarrhea among a population
      based cohort of 397 children aged <3 years residing in rural Egypt from 1995 to
      1998. The age-specific incidence rates of astrovirus diarrheal episodes per
      person-year were 0.38 for infants aged <6 months, 0.40 for those aged 6-11
      months, 0.16 for those aged 12-23 months, and 0.05 for those aged 24-35 months.
      The overall incidence rate of astrovirus diarrhea was the same as that of
      rotavirus diarrhea, 0.19 episodes per person-year. Astrovirus infection was
      pathogenic and associated with severe dehydration in 17% of the cases. The most
      frequent serotype was HAstV-1, and, in order of decreasing frequency, HAstV-5,
      HAstV-8 and HAstV-3, HAstV-6, HAstV-4, and HAstV-2. In determining whether
      astrovirus diarrhea was associated with a reduced incidence of subsequent
      disease, there was evidence to suggest HAstV-1 homotypic immunity but not
      heterotypic immunity. Because we observed 38% of the incidence of astrovirus
      diarrhea to occur in infants aged <6 months, a candidate astrovirus vaccine would
      have to confer immunity very early in life.

PMID- 10950761
TI  - Genetic diversity and molecular epidemiology of Norwalk-like viruses.
AB  - Specimens (n=287) from 59 gastroenteritis outbreaks collected from February 1997
      to March 1999 were analyzed by reverse transcriptase-polymerase chain reaction.
      The majority of outbreaks (88%) were associated with Norwalk-like viruses.
      Molecular analyses of strains from 46 outbreaks showed the cocirculation during
      the 1998-1999 winter of 2 genogroup II clusters, accounting for 57% and 28% of
      outbreaks, respectively. An important genetic diversity was observed during this
      2-year period. Thirteen different genogroup II strains and 3 different genogroup
      I strains were found. Genogroup I strains, although from the same cluster, were
      highly divergent (9%-16%). Epidemiologic and molecular data indicate that several
      introductions did not result in any major shift of prominent strains, whereas 1
      apparently established itself. Some point mutations allowed corroboration of
      epidemiologic links and strongly suggest that, in several instances, sharing
      staff and/or transfer of patients between health care institutions can create a
      significant risk for Norwalk-like virus dissemination.

PMID- 10950763
TI  - Estrogen protects against vaginal transmission of simian immunodeficiency virus.
AB  - Postmenopausal women and women who use injectable, progestin-based contraceptives
      are at increased risk of human immunodeficiency virus (HIV) infection, suggesting
      that progesterone and estrogen affect HIV-1 vaginal transmission. To evaluate the
      individual roles of these sex hormones in vaginal transmission, ovariectomized
      female macaques were treated with either progesterone or estrogen followed by
      intravaginal inoculation with SIVmac. All 6 untreated control macaques and 5
      (83%) of 6 progesterone-treated animals became infected following intravaginal
      SIV inoculation. Conversely, none of 6 estrogen-treated macaques was infected.
      Vaginal subepithelial inoculation of estrogen-treated animals resulted in
      infection, which shows that the block occurred at the vaginal epithelium and/or
      lumen. These data suggest that estrogen-deficient women are at increased risk of
      HIV infection, because their vaginal microenvironments are rendered more
      susceptible. Moreover, topical vaginal estrogen therapy may be an effective means
      of reducing HIV vaginal transmission in these high-risk groups.

PMID- 10950762
TI  - Genetic epidemiology of hepatitis C virus throughout egypt.
AB  - Hepatitis C virus (HCV) infection is a major health problem in Egypt, where the
      seroprevalence is 10-20-fold higher than that in the United States. To
      characterize the HCV genotype distribution and concordance of genotype
      assessments on the basis of multiple genomic regions, specimens were obtained
      from blood donors in 15 geographically diverse governorates throughout Egypt. The
      5' noncoding, core/E1, and NS5B regions were amplified by reverse transcription
      polymerase chain reaction and analyzed by both restriction fragment length
      polymorphism (RFLP) and phylogenetic tree construction. For the 5' noncoding
      region, 122 (64%) of 190 specimens were amplified and analyzed by RFLP: 111 (91%)
      were genotype 4, 1 (1%) was genotype 1a, 1 (1%) was genotype 1b, and 9 (7%) could
      not be typed. Phylogenetic analyses of the core/E1 and NS5B regions confirmed the
      genotype 4 preponderance and revealed evidence of 3 new subtypes. Analysis of
      genetic distance between isolates was consistent with the introduction of
      multiple virus strains 75-140 years ago, and no clustering was detected within
      geographic regions, suggesting widespread dispersion at some time since then.

PMID- 10950764
TI  - Homozygosity for a conserved Mhc class II DQ-DRB haplotype is associated with
      rapid disease progression in simian immunodeficiency virus-infected macaques:
      results from a prospective study.
AB  - In human immunodeficiency virus type 1 (HIV-1)-infected individuals, disease
      progression varies considerably. This is also observed after experimental
      infection of macaques with simian immunodeficiency virus (SIV). Major
      histocompatibility complex (MHC) genes may influence disease progression in both
      species. Homozygosity for Mhc-Mamu (Macaca mulatta)-DQB1*0601 was previously
      identified to be associated with rapid disease progression in SIV-infected
      macaques. To validate the association of this genotype with disease progression,
      a prospective study was carried out. Six unrelated monkeys homozygous for Mamu
      DQB1*0601 and DRB1*0309-DRB*W201 and 6 heterozygous monkeys were infected with
      SIVmac. Five of the homozygous and only 1 of the heterozygous monkeys died
      rapidly after infection, with manifestations of AIDS. These results were
      validated by a retrospective survival analysis of 71 SIV-infected monkeys. The
      identified DQ-DRB genotype is frequent among monkeys of different breeding
      colonies and allows a fairly reliable selection before infection of monkeys
      predisposed for rapid disease progression.

PMID- 10950765
TI  - Effects of multiple acute morphine exposures on feline immunodeficiency virus
      disease progression.
AB  - Drug abuse is a common method of human immunodeficiency virus type 1
      transmission, but the role of opiates on lentivirus disease progression is not
      well understood. The feline immunodeficiency virus (FIV)/cat system was used to
      model the weekend opiate abuser: the nondependent, nonaddicted, and nontolerant
      person. Sixteen cats were placed into 4 groups: FIV only, morphine only,
      morphine/FIV, and controls. Multiple acute morphine exposure did not increase the
      severity of early lentivirus infection. On the contrary, it delayed or moderated
      the FIV-induced disease progression. Although the animals were exposed to only 1
      injection of morphine per day for 2 consecutive days per week, the morphine
      treated FIV-infected animals had a delayed onset of the FIV-induced
      lymphadenopathy, did not develop or had a significant delay in the FIV-induced
      effects on brain stem auditory evoked potentials, and demonstrated a trend toward
      decreased virus load.

PMID- 10950766
TI  - Baseline human immunodeficiency virus type 1 phenotype, genotype, and RNA
      response after switching from long-term hard-capsule saquinavir to indinavir or
      soft-gel-capsule saquinavir in AIDS clinical trials group protocol 333.
AB  - AIDS Clinical Trials Group protocol 333 was an open-label trial of a switch from
      saquinavir (SQV) hard capsules (SQVhc) to indinavir (IDV) or saquinavir soft-gel
      capsules (SQVsgc) after >48 weeks of prior treatment with SQVhc. Eighty-nine
      subjects received IDV or SQVsgc or continued to receive SQVhc and continued
      unchanged treatment with non-protease-inhibitor antivirals for 8 weeks. Subjects
      receiving SQVhc then switched treatment to IDV. Baseline drug susceptibility and
      protease gene sequencing were done; 12 codons related to IDV and SQV resistance
      were analyzed. After 112 weeks (median) of SQVhc, the fall in human
      immunodeficiency virus (HIV) type 1 RNA level from baseline was significantly
      greater with IDV and was inversely correlated with the number of protease
      substitutions. The number of substitutions also correlated with baseline CD4 cell
      count, HIV-1 RNA level, SQV experience, and drug susceptibility. Substitution at
      codon 10, which occurred only in isolates with >/=2 substitutions, was associated
      with blunted RNA response. IDV IC(50) correlated with HIV-1 RNA response after
      the switch to IDV but added little predictive power once the genotype was
      considered.

PMID- 10950767
TI  - The danish protease inhibitor study: a randomized study comparing the virological
      efficacy of 3 protease inhibitor-containing regimens for the treatment of human
      immunodeficiency virus type 1 infection.
AB  - The Danish Protease Inhibitor (PI) Study has enrolled 318 human immunodeficiency
      virus (HIV)-infected, PI-naive patients for the purpose of comparing 3 PI
      containing regimens for the treatment of HIV infection. The regimens include 2
      nucleoside analogues in combination with indinavir (Idr), ritonavir (Rtv), or Rtv
      and saquinavir (Rtv/Sqv). Similar percentages of patients in the 3 study arms
      achieved reduced levels (</=20 copies/mL) of HIV RNA. In the area under the curve
      minus baseline analyses, a better response was found in the Rtv/Sqv arm than in
      the Rtv arm. No difference was found when comparing Rtv/Sqv with Idr and Rtv with
      Idr. Patients in the 3 arms had comparable increases in CD4 cell counts. At 72
      weeks of follow-up, there was no statistical difference between arms for the
      primary study end point (</=20 HIV RNA copies/mL); however, some of the
      additional analyses indicated an advantage for the Rtv/Sqv arm, especially when
      compared with the Rtv arm.

PMID- 10950768
TI  - Recovery of replication-competent virus from CD4 T cell reservoirs and change in
      coreceptor use in human immunodeficiency virus type 1-infected children
      responding to highly active antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) suppresses plasma viremia in most
      patients with human immunodeficiency virus (HIV) infection. Prospective study of
      HIV-infected children (n=27) shows that, in 8 of 12 who responded to HAART
      (>/=0.5 log reduction in plasma HIV RNA), HAART restricted the number of
      coreceptors used by the predominant HIV isolate (mean number of coreceptors used
      at baseline was 4, vs. 1 coreceptor used at 6 months after treatment). This
      decrease was most striking in 6 of 8 children whose HIV coreceptor tropism
      changed from X4-tropic at baseline to R5-tropic. In 6 of 10 children tested, with
      plasma HIV RNA levels of <50 copies/mL, R5-tropic virus was isolated from CD4 T
      cell reservoirs. All the responding children had a significant increase in naive
      CD4 T cells (P<.05). These results show that persistent HIV T cell reservoirs are
      present in children and that HAART may influence the number and type of
      coreceptors used by the predominant virus isolate.

PMID- 10950770
TI  - Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell
      responses in chronically infected persons after temporary treatment interruption.
AB  - Immunologic and virologic outcomes of treatment interruption were compared for 5
      chronically human immunodeficiency virus (HIV)-infected persons who have
      maintained antiretroviral therapy-mediated virus suppression, as compared with 5
      untreated controls. After a median interruption of 55 days of therapy accompanied
      by rebound of virus, reinitiated therapy in 4 of 5 subjects resulted in
      suppression of 98.86% of plasma virus load by 21-33 days and no significant
      decrease in CD4 T cell percentage from baseline. Increased T helper responses
      against HIV-1 p24 antigen (P=. 014) and interferon-gamma-secreting CD8 T cell
      responses against HIV-1 Env (P=.004) were present during interruption of therapy
      and after reinitiation of treatment. The remaining subject whose treatment was
      interrupted did not resume treatment and continued to have a low virus load
      (<1080 HIV-1 RNA copies/mL) and persistent antiviral cell-mediated responses. In
      summary, cellular immunity against autologous HIV-1 has the potential to be
      acutely augmented in association with temporary treatment interruption in
      chronically infected persons.

PMID- 10950769
TI  - Drug resistance and predicted virologic responses to human immunodeficiency virus
      type 1 protease inhibitor therapy.
AB  - The extent to which human immunodeficiency virus (HIV) type 1 drug resistance
      compromises therapeutic efficacy is intimately tied to drug potency and exposure.
      Most HIV-1 protease inhibitors maintain in vivo trough levels above their human
      serum protein binding-corrected IC(95) values for wild-type HIV-1. However, these
      troughs are well below corrected IC(95) values for protease inhibitor-resistant
      viruses from patients experiencing virologic failure of indinavir and/or
      nelfinavir. This suggests that none of the single protease inhibitors would be
      effective after many cases of protease inhibitor failure. However, saquinavir,
      amprenavir, and indinavir blood levels are increased substantially when each is
      coadministered with ritonavir, with 12-h troughs exceeding corrected wild-type
      IC(95) by 2-, 7-, and 28-79-fold, respectively. These indinavir and amprenavir
      troughs exceed IC(95) for most protease inhibitor-resistant viruses tested. This
      suggests that twice-daily indinavir-ritonavir and, to a lesser extent, amprenavir
      ritonavir may be effective for many patients with viruses resistant to protease
      inhibitors.

PMID- 10950771
TI  - Human immunodeficiency virus type 1 infection modulates the interleukin (IL)
      1beta and IL-6 responses of human macrophages to CD40 ligand stimulation.
AB  - Better understanding of the mechanisms of proinflammatory cytokine production
      during human immunodeficiency virus (HIV) type 1 infection is of pivotal
      importance. The effect of HIV-1 infection on recombinant CD40 ligand (CD40L)
      induced interleukin (IL)-1beta and IL-6 production by human macrophages was
      analyzed. ELISA and cytofluorometric analysis demonstrated that CD40L stimulation
      of HIV-1-infected macrophages resulted in substantial production of IL-1beta and
      IL-6. In contrast, no cytokine response was observed in uninfected cells. No
      modulation of the receptor for CD40 was found to account for the enhanced
      response to CD40L. The CD40L effect was not due to lipopolysaccharide
      contamination and was completely abrogated by preincubation with a monoclonal
      anti-CD40L antibody. mRNA studies indicated that the priming effect of HIV-1 on
      the macrophage response to CD40L was regulated at the transcriptional level.
      Finally, the effect of HIV-1 on the cytokine response could not be abolished by
      the HIV-1 protease inhibitor U75875 at concentrations that completely suppressed
      HIV-1 replication.

PMID- 10950772
TI  - Lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and are the
      likely target cell for human immunodeficiency virus type 1 in the intestinal
      mucosa.
AB  - Most human immunodeficiency virus type 1 (HIV-1) infections are acquired via
      mucosal surfaces, and transmitted viruses are nearly always macrophage-tropic,
      suggesting that mucosal macrophages participate in early HIV-1 infection. Mucosal
      lymphocytes isolated from normal human intestine expressed CD4 (14,530+/-7970
      antibody-binding sites [ABSs]/cell), CCR5 (2730+/-1524 ABSs/cell), and CXCR4
      (2507+/-1840 ABSs/cell), but intestinal macrophages, which also expressed CD4
      (2959+/-2695 ABSs/cell), displayed no detectable CCR5 or CXCR4 ABS. The absence
      of CCR5 on intestinal macrophages was not due to expression of the Delta32
      deletion allele because matched-blood monocytes expressed CCR5. CCR5(+)CXCR4(+)
      intestinal lymphocytes supported both R5 (BaL) and X4 (IIIB) HIV-1 replication,
      whereas the CCR5(-)CXCR4(-) macrophages were not permissive to either isolate or
      other laboratory isolates (ADA and DJV) and primary isolates (MDR 24 and JOEL).
      In the intestinal mucosa, lymphocytes, not macrophages, are the likely target
      cell for R5 (and X4) HIV-1 and are the major source of HIV-1 production during
      early infection.

PMID- 10950773
TI  - Loss of CD4+ T cell proliferative ability but not loss of human immunodeficiency
      virus type 1 specificity equates with progression to disease.
AB  - In this study, we compared human immunodeficiency virus (HIV) type 1-specific
      proliferative responses with HIV-1-induced intracellular cytokine production in a
      cohort of clinically nonprogressing patients and individuals with progressive HIV
      1 infection. We found strong HIV-1-specific proliferative responses in the
      clinical nonprogressor cohort that correlated with significant numbers of
      circulating HIV-1-specific CD4(+) T cells. In contrast, HIV-1-specific
      proliferative responses were absent in most individuals with progressive HIV-1
      infection, even though interferon-gamma-producing HIV-1-specific CD4(+) T cells
      were detectable by flow cytometry. The implication of these data is that the
      important dysfunction seen in most HIV-positive patients from very early in
      disease may be an inability of HIV-1-specific CD4(+) memory T cells to
      proliferate in response to HIV antigens rather than an absolute loss of
      circulating virus-specific CD4(+) T cells.

PMID- 10950774
TI  - Clostridial gas gangrene. I. Cellular and molecular mechanisms of microvascular
      dysfunction induced by exotoxins of Clostridium perfringens.
AB  - Mechanisms responsible for the rapid tissue destruction in gas gangrene are not
      well understood. To examine the early effects of Clostridium perfringens
      exotoxins on tissue perfusion, a rat model of muscle blood flow was developed.
      Intramuscular injection of a clostridial toxin preparation containing both
      phospholipase C (PLC) and theta-toxin caused a rapid (1-2 min) and irreversible
      decrease in blood flow that paralleled formation of activated platelet aggregates
      in venules and arterioles. Later (20-40 min), aggregates contained fibrin and
      leukocytes, and neutrophils accumulated along vascular walls. Flow cytometry
      confirmed that these clostridial toxins or recombinant PLC induced formation of P
      selectin-positive platelet aggregates. Neutralization of PLC activity in the
      clostridial toxin preparation completely abrogated human platelet responses and
      reduced perfusion deficits. It is concluded that tissue destruction in gas
      gangrene is related to profound attenuation of blood flow initiated by activation
      of platelet responses by PLC.

PMID- 10950775
TI  - Clostridial gas gangrene. II. Phospholipase C-induced activation of platelet
      gpIIbIIIa mediates vascular occlusion and myonecrosis in Clostridium perfringens
      gas gangrene.
AB  - Clostridium perfringens gas gangrene is a fulminant infection, and radical
      amputation remains the single best treatment. It has been hypothesized that rapid
      tissue destruction is related to tissue hypoxia secondary to toxin-induced
      vascular obstruction, and previous studies demonstrated that phospholipase C
      (PLC) caused a rapid and irreversible decrease in skeletal muscle blood flow that
      paralleled the formation of intravascular aggregates of activated platelets,
      fibrin, and leukocytes. In this study, flow cytometry demonstrated that PLC
      stimulated platelet/neutrophil aggregation in a gpIIbIIIa-dependent fashion.
      Pretreatment of animals with heparin or depletion of leukocytes reduced blood
      flow deficits, and aggregate formation caused by PLC. It is concluded that
      fulminant tissue destruction in gas gangrene results from profound attenuation of
      blood flow caused by PLC-induced, gpIIbIIIa-mediated formation of heterotypic
      platelet/polymorphonuclear leukocyte aggregates. Therapeutic strategies that
      target gpIIbIIIa may prevent vascular occlusion, maintain tissue viability, and
      provide an alternative to radical amputation for patients with this infection.

PMID- 10950776
TI  - Host specificity of vancomycin-resistant Enterococcus faecium.
AB  - Amplified-fragment length polymorphism (AFLP) analysis was used to investigate
      the genetic relationships among 255 vancomycin-resistant Enterococcus faecium
      (VREF) strains isolated from hospitalized patients, nonhospitalized persons, and
      various animal sources. Four major AFLP genogroups (A-D) were discriminated. The
      strains of each taxon shared >/=65% of the restriction fragments. Most isolates
      recovered from nonhospitalized persons (75%) were grouped together with all pig
      isolates in genogroup A. Most isolates from hospitalized patients (84%), a subset
      of veal calf isolates (25%), and all isolates from cats and dogs clustered in
      genogroup C. Most isolates from chickens (97%) and turkeys (86%) were grouped in
      genogroup B, whereas most veal calf isolates (70%) clustered in genogroup D.
      Therefore, VREF strains are predominantly host-specific, and strains isolated
      from hospitalized patients are genetically different from the prevailing VREF
      strains present in the fecal flora of nonhospitalized persons.

PMID- 10950777
TI  - Severity of group B streptococcal arthritis is correlated with beta-hemolysin
      expression.
AB  - Septic arthritis is a clinical manifestation of group B streptococcal (GBS)
      infection in neonates and adults. To examine the potential role of GBS beta
      hemolysin in joint injury, mice were infected with 2 wild-type strains or with
      nonhemolytic (NH) or hyperhemolytic (HH) variants derived by transposon
      mutagenesis. Compared with mice infected with the parent strains, mice infected
      with the NH mutants had decreased mortality and bacterial proliferation. A
      reduced LD(50) and a higher microbial load were obtained in mice infected with
      the HH mutants. Greater degrees of joint inflammation and damage were observed in
      the HH mutant-infected animals than in those infected with the parental strains.
      NH mutant-infected mice manifested only a mild and transient arthritis. Systemic
      and local levels of interleukin-6 mirrored the observed differences in virulence
      and severity of arthritis. These data support a direct correlation of GBS beta
      hemolysin expression with mortality and severity of articular lesions.

PMID- 10950778
TI  - Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5
      countries.
AB  - A multicenter study was done during 1993-1995 to investigate prospectively the
      influence of several prognostic factors for predicting the risk of death among
      patients with pneumococcal bacteremia. Five centers located in Canada, the United
      Kingdom, Spain, Sweden, and the United States participated. Clinical parameters
      were correlated to antibiotic susceptibility and serotyping of the 354 invasive
      pneumococcal isolates collected and to molecular typing of 173 isolates belonging
      to the 5 most common serotypes (14, 9V, 23F, 3, and 7F). Serotype 14 was the most
      common among all isolates, but serotype 3 dominated in fatal cases and in
      isolates from Spain and the United States, the countries with the highest case
      fatality rates. Fewer different patterns were found among the type 3 isolates,
      which suggests a closer clonal relationship than that among isolates belonging to
      other serotypes. Of type 3 isolates from fatal cases, 1 clone predominated. Other
      penicillin-susceptible invasive clones were also shown to spread in and between
      countries.

PMID- 10950779
TI  - Prospective study of prognostic factors in community-acquired bacteremic
      pneumococcal disease in 5 countries.
AB  - To define the influence of prognostic factors in patients with community-acquired
      pneumococcal bacteremia, a 2-year prospective study was performed in 5 centers in
      Canada, the United States, the United Kingdom, Spain, and Sweden. By multivariate
      analysis, the independent predictors of death among the 460 patients were age >65
      years (odds ratio [OR], 2.2), living in a nursing home (OR, 2.8), presence of
      chronic pulmonary disease (OR, 2.5), high acute physiology score (OR for scores 9
      14, 7.6; for scores 15-17, 22; and for scores >17, 41), and need for mechanical
      ventilation (OR, 4.4). Of patients with meningitis, 26% died. Of patients with
      pneumonia without meningitis, 19% of those with >/=2 lobes and 7% of those with
      only 1 lobe involved (P=.0016) died. The case-fatality rate differed
      significantly among the centers: 20% in the United States and Spain, 13% in the
      United Kingdom, 8% in Sweden, and 6% in Canada. Differences of disease severity
      and of frequencies and impact of underlying chronic conditions were factors of
      probable importance for different outcomes.

PMID- 10950780
TI  - Intranasal immunization with gonococcal outer membrane preparations reduces the
      duration of vaginal colonization of mice by Neisseria gonorrhoeae.
AB  - Nasal immunization was studied to determine if it could elicit an immune response
      capable of preventing vaginal colonization by Neisseria gonorrhoeae or of
      reducing its duration in the estradiol-treated mouse model. Nasal administration
      of gonococcal outer membrane (OM) preparations induced the development of
      systemic and vaginal immune responses that were directed mainly against a limited
      number of gonococcal OM proteins. The impact of nasal immunization on vaginal
      colonization by N. gonorrhoeae was evaluated by use of an experimental model, in
      which mice were treated with estradiol to prolong the infection. Bacterial
      clearance was significantly faster for mice immunized intranasally with N.
      gonorrhoeae OM preparations (4.0+/-2.5 days) than for control mice (8.5+/-4.3
      days). The estradiol-treated mouse model may serve as a useful tool for the
      evaluation of potential gonococcal vaccine candidates.

PMID- 10950781
TI  - In vivo disruption of the fas pathway abrogates gastric growth alterations
      secondary to Helicobacter infection.
AB  - Helicobacter infection is associated with gastric cell growth alterations,
      plausibly predisposing to ulcer disease and gastric adenocarcinoma. Previous
      investigations from our laboratory have implicated the involvement of the Fas
      pathway in Helicobacter-induced apoptotic signaling in vitro. In this report we
      use C57BL/6J00064 mice to examine the direct role of Fas signaling in
      Helicobacter-mediated growth alterations in vivo. Helicobacter infection up
      regulated gastric cell Fas antigen (Fas Ag) mRNA and increased surface receptor
      expression, along with concomitant altered apoptotic and proliferative response,
      measured by terminal deoxytransferase-deoxyuridine 5'-triphosphate nick end
      labeling and 5-bromo-2'-deoxuridine immunohistochemistry, respectively. In
      addition, histopathological alterations, including parietal cell loss and gastric
      atrophy, were noted. In contrast, infection in B6. MRL-FAS(lpr), a Fas Ag
      knockout mouse in the C57BL/6 background, did not result in increased apoptosis,
      proliferation, or histological alterations, a finding that argues strongly for
      the role of Fas-signaling pathway in orchestrating diverse growth responses to
      Helicobacter infection.

PMID- 10950782
TI  - Natural history of infection with Bartonella bacilliformis in a nonendemic
      population.
AB  - An investigation was performed after an outbreak of bartonellosis in a region of
      Peru nonendemic for this disorder. Symptoms of acute and chronic bartonellosis
      were recorded. Serological analysis was performed on 55% of the affected
      population (554 individuals), 77.5% of whom demonstrated previous infection with
      Bartonella bacilliformis. The attack rate of Oroya fever was 13.8% (123 cases);
      the case-fatality rate was 0.7%. The attack rate of verruga peruana was 17.6%. A
      new specific immunostain was developed and used to confirm the presence of B.
      bacilliformis in the biopsied skin lesions. Most seropositive individuals (56%)
      were asymptomatic. The symptoms that were associated with prior infection, as
      determined by Western blot, included fever (37.2% of the seropositive vs. 17.2%
      of the seronegative population; P<.001), bone and joint pain (27% vs. 9%;
      P<.001), headache (27% vs. 12.3%; P <.001), and skin lesions described as verruga
      peruana (26.8% vs. 4.9%; P<.001). Our findings suggest that infection with B.
      bacilliformis causes a broad spectrum of disease that is significantly milder in
      severity than that frequently reported.

PMID- 10950783
TI  - Localization of endotoxin in the rat intestinal epithelium.
AB  - High levels of circulating lipopolysaccharide (LPS) cause intestinal inflammation
      and increased permeability to bacteria and toxins. To better understand the
      effects of LPS on the gut, confocal microscopy and immunofluorescence staining
      were used to examine the distribution of LPS in the rat intestine after
      intravenous or enteral administration. LPS was localized in macrophages in the
      lamina propria from 1 h to >28 days after intravenous injection. LPS was also
      detected in the epithelial cells from 8 h to 7 days after injection. In contrast,
      LPS administered enterally was found in the gut lumen in close proximity to the
      mucosa but was not detected in enterocytes at any time. The concentration of LPS
      in enterocytes near the villus tip provides a mechanism for the clearance of
      endotoxin, by the turnover and shedding of LPS-containing enterocytes into the
      gut lumen, that has not been previously described.

PMID- 10950784
TI  - Induction of mucin gene expression in middle ear of rats by tumor necrosis factor
      alpha: potential cause for mucoid otitis media.
AB  - Mucoid otitis media (MOM) is characterized by viscous fluid, high in mucin
      concentration, which accumulates in the middle ear cavity. Recent studies suggest
      that initial infection in the middle ear cleft may be key to the development of
      MOM. However, factors of the initial infection attributed to the stimulation of
      mucin production are not clearly understood. This study demonstrated that tumor
      necrosis factor (TNF)-alpha, a proinflammatory cytokine in mucoid effusion,
      markedly increased Muc2 mucin mRNA expression in middle ear epithelium, in a time
      and dose-dependent manner. Parallel to this was a marked increase in mucin
      glycoprotein in middle ear fluid. Also, TNF-alpha demonstrated an autocrine
      and/or paracrine effect on the expression of endogenous TNF-alpha gene in the
      middle ear, which may contribute to the production of mucin in this study. These
      findings suggest that TNF-alpha plays an important role in the development of MOM
      by stimulating mucin metabolism.

PMID- 10950785
TI  - Expression of the chemokine receptors CXCR1 and CXCR2 on granulocytes in human
      endotoxemia and tuberculosis: involvement of the p38 mitogen-activated protein
      kinase pathway.
AB  - The chemokine receptors CXCR1 and CXCR2 critically determine the functional
      properties of granulocytes. To obtain insight in the regulation of these
      receptors during infection, CXCR expression was determined on blood granulocytes
      by fluorescence-activated cell sorter analysis in healthy subjects intravenously
      injected with lipopolysaccharide (LPS) and in patients with active tuberculosis.
      In healthy subjects, LPS induced a transient decrease in granulocyte CXCR1 and
      CXCR2 expression, whereas in tuberculosis patients, only CXCR2 showed reduced
      levels. In whole blood in vitro, LPS, lipoarabinomannan from Mycobacterium
      tuberculosis, and lipoteichoic acid from Staphylococcus aureus reduced expression
      of CXCR2 but not of CXCR1. CXCR2 down-regulation induced by LPS or tumor necrosis
      factor-alpha in vitro was abrogated by a p38 mitogen-activated protein kinase
      (MAPK) inhibitor. Granulocytes may down-regulate CXCR2 and, to a lesser extent,
      CXCR1 at their surface upon their first interaction with mycobacterial or
      bacterial pathogens by a mechanism that involves activation of p38 MAPK.

PMID- 10950786
TI  - Evaluation of human antimycobacterial immunity using recombinant reporter
      mycobacteria.
AB  - A novel in vitro whole blood model was developed to study human antimycobacterial
      immunity. Recombinant reporter mycobacteria were used to enumerate the bacteria,
      and interactions between host immune cells and mycobacteria were studied using
      whole blood rather than cell fractions. The ability of healthy tuberculin
      positive and tuberculin-negative individuals to restrict mycobacterial growth was
      compared. Growth of luminescent mycobacteria was significantly lower in blood
      samples of tuberculin-positive individuals than in blood samples of tuberculin
      negative individuals (P=.005). Restricted mycobacterial growth was associated
      with significantly higher production of tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma (P=.01 and.004, respectively). Inhibition of the TNF-alpha
      and IFN-gamma response pathways by neutralizing monoclonal antibodies increased
      mycobacterial growth in whole blood. This model is the first functional assay in
      which individual variations in cell-mediated immunity are shown to correlate with
      differences in ability to control mycobacterial growth. It provides a new tool
      for studying human mycobactericidal mechanisms and, potentially, for the
      evaluation of improved vaccines.

PMID- 10950787
TI  - Interleukin-1 signaling is essential for host defense during murine pulmonary
      tuberculosis.
AB  - Interleukin (IL)-1 signaling is required for the containment of infections with
      intracellular microorganisms, such as Listeria monocytogenes and Leishmania
      major. To determine the role of IL-1 in the host response to tuberculosis, we
      infected IL-1 type I receptor-deficient (IL-1R(-/-)) mice, in which IL-1 does not
      exert effects, with Mycobacterium tuberculosis. IL-1R(-/-) mice were more
      susceptible to pulmonary tuberculosis, as reflected by an increased mortality and
      an enhanced mycobacterial outgrowth in lungs and distant organs, which was
      associated with defective granuloma formation, containing fewer macrophages and
      fewer lymphocytes, whereas granulocytes were abundant. Lymphocytes were
      predominantly confined to perivascular areas, suggesting a defective migration of
      cells into inflamed tissue in the absence of IL-1 signaling. Impaired host
      defense in IL-1R(-/-) mice was further characterized by a decrease in the ability
      of splenocytes to produce interferon-gamma. Analysis of these data suggests that
      IL-1 plays an important role in the immune response to M. tuberculosis.

PMID- 10950788
TI  - Evidence for long-term cervical persistence of Chlamydia trachomatis by omp1
      genotyping.
AB  - Recurrent Chlamydia trachomatis infections are common among sexually active
      women. Although recurrences with a new chlamydial serovar indicate reinfection,
      same-serovar recurrences may be due to persistence. Because persistence has
      important implications for pathogenesis and patient management, we identified 552
      women with >3 recurrences over 2 years. Among these, 130 women (24%) had same
      serovar recurrences; 58 (45%) were C class serovars (odds ratio, 2.4; 95%
      confidence interval, 1.7-3.5; P<.0001). Forty-five isolates from 7 women with 3
      10 repeated, same-serovar infections over 2-5 years were studied. As determined
      by omp1 genotyping, 4 women had identical genotypes at each recurrence; 2 women
      had 1 or 2 amino acid changes following treatment, and one was persistently
      infected with a unique genotype, Ja. Many intervening culture-negative samples
      were positive when tested by ligase chain reaction, which suggests persistence.
      These data demonstrate that cervical infections with C class serovars can persist
      for years and may have specific biologic properties that allow for modulation of
      the major outer membrane protein in response to immune selection.

PMID- 10950789
TI  - Role of pulmonary surfactant protein D in innate defense against Candida
      albicans.
AB  - Pulmonary surfactant protein D (SP-D), which is a member of the collectin family,
      is implicated in pulmonary defense against pathogens. To determine whether SP-D
      is involved in first-line immunity against Candida albicans, an important
      respiratory fungus, the interaction of SP-D with C. albicans was studied. SP-D
      was found to bind C. albicans, resulting in agglutination of the microorganisms.
      Binding was calcium dependent and was inhibited by competing sugars maltose or
      mannose. Incubation of C. albicans with SP-D resulted in profound fungal growth
      inhibition and decreased hyphal outgrowth. Furthermore, it was found that SP-D
      inhibited phagocytosis of C. albicans by alveolar macrophages. These data suggest
      that the lung collectin SP-D has an important role in first-line defense against
      C. albicans in the lung, by agglutinating C. albicans and limiting their growth,
      without the need for macrophage activation.

PMID- 10950790
TI  - Intraocular T cells of patients with herpes simplex virus (HSV)-induced acute
      retinal necrosis recognize HSV tegument proteins VP11/12 and VP13/14.
AB  - It has previously been shown that T cells specific for the triggering virus
      infiltrate the eye of patients with herpes simplex virus type 1 (HSV-1)-induced
      acute retinal necrosis (ARN). The T cells were mainly directed against 0.67-0.73
      HSV-1 map region encoded antigens. The fine specificities of genetically
      different T cell clones (TCC), obtained from affected eyes of 3 patients with HSV
      induced ARN and reactive toward this genomic region of HSV-1, were analyzed with
      recombinant HSV viruses and synthetic peptides. For 1 patient, the HSV-1 UL46
      gene encoded tegument protein VP11/12 was identified as the target antigen. Two
      separate CD4(+) T cell epitopes were defined in VP11/12. TCC from the other 2
      patients recognized the HSV-1 UL47 gene encoded tegument protein VP13/14. Two
      separate CD4(+) VP13/14 T cell epitopes were identified in these patients.
      Analysis of the data indicates that HSV-1 VP11/12 and VP13/14 are major target
      antigens for T cells obtained from vitreous fluid samples of the HSV-induced ARN
      patients studied.

PMID- 10950792
TI  - Intrauterine cytomegalovirus infection and glycoprotein B genotypes.
AB  - Cytomegalovirus (CMV) strains display polymorphisms for the gene encoding
      glycoprotein B (gB; gpUL55). Recent data suggest that the gB genotype may
      influence the outcome of acquired CMV infections. To determine whether the gB
      genotype also contributes to the outcome of intrauterine infection, CMV strains
      were studied from 56 infants with culture-confirmed intrauterine CMV infections
      who were born in Iowa or Texas. CMV gB genotypes were compared with the neonatal
      clinical features and neurodevelopmental outcomes. Fifty-three strains (95%)
      could be assigned a gB genotype. The overall distribution of genotypes was as
      follows: type 1, 50%; type 2, 18%; type 3, 23%; and type 4, 4%. Strains with the
      gB 3 genotype were more common among the Iowa infants (P=.082). The gB 3 genotype
      was more common among infants with asymptomatic infections (P=.004), but
      geographic location and ascertainment biases may have accounted for these
      differences. The gB genotypes did not correlate with the neurodevelopmental
      outcome of intrauterine infection.

PMID- 10950791
TI  - CD8+ cytotoxic T lymphocyte responses to lytic proteins of human herpes virus 8
      in human immunodeficiency virus type 1-infected and -uninfected individuals.
AB  - T cell immunity to lytic proteins of herpesviruses is important in host control
      of infection. We have characterized the cytotoxic T lymphocyte (CTL) response to
      5 human herpesvirus 8 (HHV-8) homologues of lytic proteins in HHV-8-seropositive
      individuals. HLA class I-restricted, CD8(+) CTL responses to >/=1 HHV-8 lytic
      protein were detected in all 14 HHV-8-seropositive study subjects tested, with or
      without human immunodeficiency virus type 1 (HIV-1) infection, but not in any of
      5 HHV-8-seronegative individuals. Seven of these study subjects with both HHV-8
      and HIV-1 infection had greater anti-CTL reactivity to glycoprotein H (open
      reading frame 22) than did the 7 study subjects infected only with HHV-8.
      Moreover, there was a strong, inverse correlation between HIV-1 load and
      glycoprotein H-specific CTL lysis in the study subjects infected with both
      viruses. CTL reactivity to HHV-8 lytic proteins may be involved in host control
      of HHV-8-related diseases, such as Kaposi's sarcoma.

PMID- 10950793
TI  - Longitudinal dynamics of Epstein-Barr virus-specific cytotoxic T lymphocytes
      during posttransplant lymphoproliferative disorder.
AB  - Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) is a
      serious complication after allogeneic bone marrow transplantation (BMT). Dynamics
      of EBV-specific cytotoxic T lymphocytes (CTL), which are important in controlling
      EBV during the LPD, have not been fully elucidated. A patient with Wiskot
      Aldrich's syndrome was diagnosed as suffering from LPD on day 47 after BMT.
      Fluorescence-activated cell sorter (FACS) analysis for interferon-gamma
      production revealed that >70% of the patient's CD8(+) T cells were EBV specific.
      The patient's lymphocytes were directly cytotoxic to donor-derived EBV-positive
      lymphoblastoid cells, which was blocked by an anti-class I antibody. EBV-specific
      CD8(+) T cell counts declined in parallel with EBV genome load, and full recovery
      of LPD was obtained with relaxation of immunosuppressive drugs. The results
      illustrate longitudinal dynamics of EBV-specific CTL during the posttransplant
      LPD; they also illustrate the advantages of using FACS analysis for EBV-specific
      CTL to make decisions about treatment.

PMID- 10950794
TI  - Molecular analysis of human immunodeficiency virus strains associated with a case
      of criminal transmission of the virus.
AB  - An investigation was done of the evidence for transmission of human
      immunodeficiency virus (HIV) from an HIV-positive man to several male and female
      sex contacts. Phylogenetic analysis of sequences from the gag and env genes
      showed a close relationship between the predominant virus strains from the source
      and 2 contacts. However, the likelihood that a female contact was infected by the
      source could not be determined, despite contact tracing indicating that this may
      have occurred. One male, shown by contact tracing and molecular evidence to have
      been infected by the source, subsequently transmitted HIV to his female sex
      partner. HIV sequence from a plasma sample used as a control in the phylogenetic
      analysis contained env and gag sequences that were closely related to those from
      the source. An epidemiologic link between these 2 individuals was subsequently
      confirmed by contact tracing.

PMID- 10950795
TI  - The effect of highly active antiretroviral therapy on binding and neutralizing
      antibody responses to human immunodeficiency virus type 1 infection.
AB  - The effect on humoral immune responses of highly active antiretroviral therapy
      (HAART) commenced during primary or chronic human immunodeficiency virus type 1
      (HIV-1) infection was investigated. HAART inhibited the development of anti-gp120
      antibodies when initiated during primary infection and could sometimes reduce
      antibody titers in patients treated within 2 years of HIV-1 infection.
      Conversely, antibody responses in patients infected for several years were less
      sensitive to HAART. Administering HAART during primary infection usually did not
      substantially affect the development of weak neutralizing antibody responses
      against autologous virus. However, 2 patients treated very early after infection
      did not develop neutralizing responses. In contrast, 3 of 4 patients
      intermittently adherent to therapy developed autologous neutralizing antibodies
      of unusually high titer, largely coincident with brief viremic periods. The
      induction of strong neutralizing antibody responses during primary HIV-1
      infection might require the suppression of virus replication by HAART, to allow
      for the recovery of immune competency, followed by exposure to native envelope
      glycoproteins.

PMID- 10950796
TI  - Virological and immunological effects of combination antiretroviral therapy with
      zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus
      type 1 infection.
AB  - Forty-seven patients presenting with primary human immunodeficiency virus (HIV)
      infection were treated with zidovudine 200 mg 3 times a day, lamivudine 150 mg 2
      times a day, and indinavir 800 mg 3 times a day for 1 year. From a mean
      pretreatment viral RNA level of 4.93 log(10) copies/mL, the proportions of
      patients having <500 copies/mL at 24 and 52 weeks were 92.0% and 89.2%,
      respectively. For the 35 patients with data available at 24 and 52 weeks, the
      corresponding proportions for the <50 copies/mL analysis were 86.6% and 79.3%,
      respectively. The change in virus load was -2.19 and -2.41 log(10) copies/mL at
      weeks 8 and 52, respectively. CD4 cell counts increased, from a mean of 546
      cells/mm(3), by 142 cells/mm(3) at week 24 and by 210 cells/mm(3) at week 52.
      Three patients discontinued the study because of drug-related toxicity. Six
      (12.8%) patients had adverse experiences associated with nephrolithiasis.
      Combination therapy with zidovudine, lamivudine, and indinavir during primary HIV
      infection results in a profound and sustained reduction in virus load with
      concurrent recovery of the CD4 cell population.

PMID- 10950797
TI  - In vivo virulence of Candida albicans isolates causing mucosal infections in
      people infected with the human immunodeficiency virus.
AB  - Mucosal candidiasis is common in human immunodeficiency virus (HIV) infection.
      Susceptibility to such infections may be attributed to reduced host defense
      mechanisms and/or virulence of the organism. In the present study, we compared
      the virulence of mucosal Candida albicans isolates from HIV-infected people, with
      and without fluconazole-refractory infection, in established murine models of
      systemic and vaginal candidiasis. Compared with the mortality rate (
      approximately 70%) after intravenous challenge with 2 virulent reference
      isolates, challenge with most clinical isolates (66%-77%) resulted in prolonged
      survival. In contrast, fungal burden induced by intravaginal challenge of nearly
      all (97%) isolates was similar to that of the virulent controls. There were no
      differences in in vitro growth rates for any of the isolates, and there was no
      association between reduced mortality and clinical failure to fluconazole, in
      vitro antifungal susceptibility, site of infection, or other host factors. These
      results suggest that virulence of C. albicans is tissue specific and is not a
      factor in the development of fluconazole-refractory infections in advanced HIV
      disease.

PMID- 10950798
TI  - Immunity to placental malaria. II. Placental antigen-specific cytokine responses
      are impaired in human immunodeficiency virus-infected women.
AB  - An association was demonstrated recently between elevated in vitro production of
      interferon (IFN)-gamma by intervillous blood mononuclear cells (IVBMCs) and
      protection against placental malaria (PM). Because human immunodeficiency virus
      (HIV)-infected pregnant women have increased susceptibility to PM, loss of the
      IFN-gamma response in these women may impair their ability to control PM.
      Measurement of cytokines in culture supernatants by ELISA revealed that IFN-gamma
      responses by HIV-positive IVBMCs were impaired, especially after malarial antigen
      stimulation. Interleukin (IL)-4 and IL-10 responses also were reduced in HIV
      positive persons, the latter more so in HIV-positive, PM-positive persons. In
      contrast, tumor necrosis factor-alpha production generally was enhanced in PM
      positive and HIV-positive persons. Overall, cytokine production was reduced in
      HIV-positive persons with CD4 T cell counts <500/microL, particularly in response
      to malarial antigen. Thus, HIV-mediated cytokine dysregulation and impairment of
      the protective IFN-gamma response may contribute to the increased susceptibility
      of HIV-positive pregnant women to malaria.

PMID- 10950799
TI  - Kinetics of antibody concentration and avidity for the assessment of immune
      response to pneumococcal vaccine among children with bone marrow transplants.
AB  - The kinetics of the immune response to the 23-valent pneumococcal polysaccharide
      vaccine (PPV) were studied in 38 children who received bone marrow transplants
      (BMTs). Anti-pneumococcal antibody concentrations increased 1 and 3 months after
      vaccination for all 5 serotypes tested, but, in 21 children, the vaccine was not
      adequately immunogenic. Children vaccinated <18 months after receiving a BMT had
      a 4.2-fold increased odds of poor response (P=. 06). Antibody concentrations
      returned close to baseline levels 9 months after vaccination. Avidity declined
      significantly as early as 1 month after vaccination and remained low thereafter.
      Antibody concentration responses to PPV were superior among 9 healthy control
      children (P=.001); 37 of 38 children with a BMT elicited adequate, persistent
      immune responses to Haemophilus influenzae conjugate vaccine. Immune responses to
      PPV in children with a BMT are suboptimal, short lived, and associated with
      declining avidity. The different kinetics of antibody concentration and avidity
      indicate that both markers should be used for evaluating pneumococcal vaccines in
      this high-risk population.

PMID- 10950800
TI  - A randomized controlled trial of filgrastim for the treatment of hospitalized
      patients with multilobar pneumonia.
AB  - This study assessed the safety and efficacy of filgrastim (r-metHuG-CSF
      [recombinant human methionine granulocyte colony-stimulating factor]), when
      combined with intravenous (IV) antibiotics, in the treatment of hospitalized
      adult patients with multilobar community-acquired pneumonia (CAP). Four hundred
      eighty patients were randomized to receive placebo (n=243) or filgrastim 300
      microg/day (n=237), in addition to standard therapy. Treatment with study drug
      was continued for 10 days, until the peak white blood cell (WBC) count reached
      75x109/L, until discharge from the hospital, until death, or until IV antibiotics
      were discontinued. Study-related observations continued through day 29.
      Filgrastim increased WBC counts (baseline median, 13.3x109/L; median peak, 43.
      8x109/L). The 2 treatment groups were not statistically different with respect to
      the study end points; however, there was a trend toward reduction of mortality in
      patients with pneumococcal bacteremia. Although further studies will be required
      to validate this observation, filgrastim was safe and well tolerated when
      administered to patients with multilobar CAP.

PMID- 10950801
TI  - Effects of group B streptococci on cord and adult mononuclear cell interleukin-12
      and interferon-gamma mRNA accumulation and protein secretion.
AB  - Group B streptococci (GBS) are a major cause of early-onset infection in
      neonates. Neonates, who have defects in neutrophil function that likely
      contribute to susceptibility to GBS infection, are deficient in the production of
      the phagocyte activator interferon (IFN)-gamma. GBS-stimulated mRNA accumulation
      and protein secretion of IFN-gamma and interleukin (IL)-12, a major enhancer of
      IFN-gamma production, by mixed mononuclear cells (MMCs) from umbilical cord and
      adult peripheral blood was examined. GBS-exposed cord blood MMCs secreted lower
      concentrations of both IL-12 and IFN-gamma proteins than did MMCs from adults. IL
      12 and IFN-gamma mRNA accumulation was examined by use of comparative reverse
      transcriptase-polymerase chain reaction. Cord blood MMCs accumulated less mRNA
      for both IL-12 and IFN-gamma than did adult blood MMC. The deficiency in cord
      blood cell production of IL-12 may have a role in inadequate IFN-gamma
      production, which contributes to the unique susceptibility of neonates to GBS
      infections.

PMID- 10950802
TI  - Antibodies to the junctional adhesion molecule cause disruption of endothelial
      cells and do not prevent leukocyte influx into the meninges after viral or
      bacterial infection.
AB  - A hallmark of infectious meningitis is the invasion of leukocytes into the
      subarachnoid space. In experimental meningitis triggered by tumor necrosis factor
      alpha and interleukin-1beta, the interaction of leukocytes with endothelial cells
      and the subsequent migration of the cells through the vessel wall can be
      inhibited by an antibody to the junctional adhesion molecule (JAM). In contrast
      to the cytokine-induced meningitis model, anti-JAM antibodies failed to prevent
      leukocyte influx into the central nervous system after infection of mice with
      Listeria monocytogenes or lymphocytic choriomeningitis virus. Furthermore, in
      bacterial meningitis, anti-JAM IgG antibodies, but not Fab fragments, caused
      disruption of the endothelium. Likewise complement-dependent antibody-mediated
      cytotoxicity was observed in cultured brain endothelial cells treated with anti
      JAM IgG but not with its Fab fragment.

PMID- 10950803
TI  - Effect of thalidomide on chemokine production by human microglia.
AB  - Thalidomide, a psychoactive drug that readily crosses the blood-brain barrier,
      has been shown to possess immunomodulatory attributes, including the inhibition
      of cytokine production by monocytes and microglia. In this study, we investigated
      the effect of thalidomide on chemokine production by human microglial cells.
      Microglial cells were stimulated with lipopolysaccharide, a key cell-wall
      component of gram-negative bacteria responsible for meningitis, and production of
      chemokines (regulated upon activation normally T cell expressed and secreted
      [RANTES], monocyte chemoattractant protein [MCP]-1, macrophage inflammatory
      protein [MIP]-1beta, and interleukin [IL]-8) was examined by ELISA. Thalidomide
      treatment was found to cause potent and selective inhibition of IL-8 production
      in a dose-responsive manner. This inhibition was associated with decreased
      intracellular IL-8 staining as well as reduced transcription of IL-8 mRNA. In
      addition, thalidomide treatment of lipopolysaccharide-stimulated microglia
      inhibited the activation of protein NF-kappaB, a transcription factor known to be
      important for IL-8 production. These results suggest thalidomide could have a
      therapeutic role in acute bacterial meningitis through inhibition of IL-8
      mediated neutrophil chemotaxis.

PMID- 10950804
TI  - Reduced interleukin-12 and transforming growth factor-beta1 in severe childhood
      malaria: relationship of cytokine balance with disease severity.
AB  - Interleukin (IL)-12 and transforming growth factor (TGF)-beta1 regulate the
      balance between pro- and anti-inflammatory cytokines in animal models of malaria.
      Since the cytokine balance may be an important determinant of whether a
      protective or a pathogenic immune response develops, plasma cytokine ratios were
      examined in Gabonese children with various degrees of malarial severity. Severe
      disease was characterized by high-density parasitemia and severe anemia. IL-12
      and TGF-beta1 were significantly lower, whereas tumor necrosis factor (TNF)-alpha
      and IL-10 were significantly higher in children with severe malaria. The ratios
      of TGF-beta1/IL-12 and IL-10/IL-12 were significantly higher in the severe,
      compared with the mild, malaria group. In contrast, ratios of TGF-beta1/TNF-alpha
      and IL-10/TNF-alpha were significantly lower in the severe malaria group. These
      results suggest that the inflammatory cascade in severe malaria is characterized
      by suppression of the protective effects of TGF-beta1 and IL-12, and that
      overproduction of TNF-alpha may promote deleterious effects, such as severe
      anemia.

PMID- 10950805
TI  - Rapid selection of Plasmodium falciparum dihydrofolate reductase mutants by
      pyrimethamine prophylaxis.
AB  - A prospective study was conducted to measure the selective effect of
      pyrimethamine prophylaxis on point mutations in Plasmodium falciparum
      dihydrofolate reductase (DHFR). A total of 109 Malian children were given
      pyrimethamine weekly for 5 weeks. P. falciparum infections were analyzed by
      polymerase chain reaction for DHFR mutations, which were dramatically more
      frequent among prophylaxis-breakthrough infections than at baseline: the
      prevalence of Asn-108 rose from 13% to 100%, Ile-51 from 4% to 50%, and Arg-59
      from 11% to 90%. Eight persistent infections lacking detectable DHFR mutations at
      baseline developed multiple mutations within 1 week of the patients' starting
      pyrimethamine prophylaxis. Microsatellite analysis found no evidence of clonal
      identity among baseline and breakthrough infections. Analysis of these data
      demonstrates that under prophylaxis conditions, pyrimethamine is strongly
      selective for DHFR mutations, which arise extremely rapidly under drug pressure,
      even when undetectable in the initial infection. These findings have implications
      for prophylaxis regimens with other antifolate drugs.

PMID- 10950806
TI  - Competence of the human host as a reservoir for Leishmania chagasi.
AB  - The failure of control programs for visceral leishmaniasis (VL) that depend on
      elimination of infected dogs suggests that other reservoir hosts may participate
      in the transmission cycle. To determine whether persons infected with Leishmania
      chagasi can infect the vector sand fly, laboratory-reared Lutzomyia longipalpis
      were allowed to feed on Brazilian subjects with active, cured, and asymptomatic
      VL and on asymptomatic residents of houses of persons with active VL. Of 3747
      insects that had fed, 26 acquired infection from 11 of the 44 persons with active
      VL, but none acquired infection from the 137 asymptomatic persons. Among persons
      <4 years old with active VL, a history of diarrhea and higher peripheral blood
      neutrophil counts were independent predictors of infectivity. Further experiments
      using larger numbers of insects are necessary to evaluate the reservoir
      competence of persons with asymptomatic infections, who represent a large segment
      of the population of several Brazilian cities.

PMID- 10950807
TI  - Interferon-gamma is required for innate immunity to Cryptosporidium parvum in
      mice.
AB  - Although CD4 T cells are required for recovery from cryptosporidial infection,
      mice with severe combined immunodeficiency (SCID) remain infected for long
      periods without ill effect. In contrast, mice whose ability to use
      interferon(IFN)-gamma is impaired, by neutralization or gene knockout, experience
      heavy cryptosporidial infection that may lead to death. To determine whether the
      innate immunity of SCID mice to Cryptosporidium parvum (CP) requires IFN-gamma,
      doubly immunodeficient C57BL/6 SCID-IFN-gamma knockout mice were bred. These mice
      experienced heavy CP infections of the gut; a significantly greater number became
      moribund or died, compared with mice carrying the SCID mutation alone or carrying
      disrupted IFN-gamma genes alone. Mice with gene disruptions of inducible nitric
      oxide synthetase or Fas/Fas ligand recovered normally from CP infection. The
      results indicate that mice unable to produce specific immune responses because of
      the SCID mutation require IFN-gamma to avoid death after infection with CP.

PMID- 10950808
TI  - Reply

PMID- 10950809
TI  - Antibody production in response to hepatitis B surface antigen in a combination
      hepatitis A/hepatitis B vaccine.

PMID- 10950810
TI  - Lack of evidence of Borrelia involvement in Alzheimer's disease.

PMID- 10950811
TI  - Helicobacter pylori infection, cagA status, and duodenal ulcer disease in
      children.

PMID- 10950812
TI  - Reply

PMID- 10950813
TI  - Osmotic and glutamate receptor regulation of c-Jun NH(2)-terminal protein kinase
      in neuroendocrine cells.
AB  - Expression of a c-Jun NH(2)-terminal protein kinase (JNK), also known as stress
      activated protein kinase (SAPK) in rodents, has been implicated in the ability of
      cells to respond to a variety of stressors. In nonmammalian cells, JNK
      participates in the regulation of cell volume in response to hyperosmotic stress.
      To explore the possibility that JNK may participate in the transduction of
      osmotic information in mammals, we evaluated the expression of JNK
      immunoreactivity in neuroendocrine cells of the supraoptic nucleus. Low basal
      expression of JNK-2 (SAPK-alpha) and JNK-3 (SAPK-beta) was seen in vivo and in
      vitro. During water deprivation, JNK-2 increased in the supraoptic nucleus but
      not in the cortex. Osmotic or glutamate receptor stimulation in vitro also
      resulted in an increase in JNK-2 that was tetrodotoxin (TTX) insensitive and
      paralleled by increased nuclear phospho-c-Jun immunoreactivity. A TTX-sensitive
      increase in JNK-3 was seen in smaller neurons. Thus different JNK pathways may
      mediate individual cellular responses to osmotic stress, with JNK-2 linked to
      osmotic and glutamate receptor stimulation in magnocellular neuroendocrine cells.

PMID- 10950814
TI  - Hypertrophied rat hearts are less responsive to the metabolic and functional
      effects of insulin.
AB  - We determined the effect of insulin on the fate of glucose and contractile
      function in isolated working hypertrophied hearts from rats with an aortic
      constriction (n = 27) and control hearts from sham-operated rats (n = 27).
      Insulin increased glycolysis and glycogen in control and hypertrophied hearts.
      The change in glycogen was brought about by increased glycogen synthesis and
      decreased glycogenolysis in both groups. However, the magnitude of change in
      glycolysis, glycogen synthesis, and glycogenolysis caused by insulin was lower in
      hypertrophied hearts than in control hearts. Insulin also increased glucose
      oxidation and contractile function in control hearts but not in hypertrophied
      hearts. Protein content of glucose transporters, protein kinase B, and
      phosphatidylinositol 3-kinase was not different between the two groups. Thus
      hypertrophied hearts are less responsive to the metabolic and functional effects
      of insulin. The reduced responsiveness involves multiple aspects of glucose
      metabolism, including glycolysis, glucose oxidation, and glycogen metabolism. The
      absence of changes in content of key regulatory molecules indicates that other
      sites, pathways, or factors regulating glucose utilization are responsible for
      these findings.

PMID- 10950815
TI  - Central neuropeptide Y stimulates ingestive behavior and increases urine output
      in the ovine fetus.
AB  - We hypothesized that central neuropeptide Y (NPY) increases swallowing activity
      and alters renal function in the near-term ovine fetus. Six ewes with singleton
      fetuses (130 +/- 2 days of gestation; 148 days = term) were chronically prepared
      with arterial and venous catheters, a fetal lateral cerebroventricular cannula,
      and fetal bladder and amniotic fluid catheters. For determination of fetal
      swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and
      the upper and lower nuchal esophagus. Electrodes were implanted on the parietal
      dura for determination of fetal electrocorticogram (ECoG). After 5 days of
      recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored
      during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered
      into the lateral ventricle, and fetuses were monitored for an additional 8 h. A
      control study of central administration of artificial cerebral spinal fluid was
      performed on an alternate day. Central NPY significantly increased swallowing
      activity during low-voltage ECoG from basal activity (1.26 +/- 0.15 swallows/min)
      at 4 h (1.93 +/- 0.37 swallows/min), 6 h (1.69 +/- 0.27 swallows/min), and 8 h
      (2.38 +/- 0.31 swallows/min). NPY significantly increased fetal urine flow
      (basal: 0.13 +/- 0.02; 4 h: 0.21 +/- 0.04; 6 h: 0. 19 +/- 0.03 ml.kg(-1).min(
      1)). These results demonstrate that central NPY stimulates fetal swallowing
      activity and increases urine output, which may contribute to the in utero
      development of ingestive behavior.

PMID- 10950816
TI  - Effects of oral administration of a synthetic fragment of human growth hormone on
      lipid metabolism.
AB  - A small synthetic peptide sequence of human growth hormone (hGH), AOD-9401, has
      lipolytic and antilipogenic activity similar to that of the intact hormone. Here
      we report its effect on lipid metabolism in rodent models of obesity and in human
      adipose tissue to assess its potential as a pharmacological agent for the
      treatment of human obesity. C57BL/6J (ob/ob) mice were orally treated with either
      saline (n = 8) or AOD-9401 (n = 10) for 30 days. From day 16 onward, body weight
      gain in AOD-9401-treated animals was significantly lower than that of saline
      treated controls. Food consumption did not differ between the two groups.
      Analyses of adipose tissue ex vivo revealed that AOD-9401 significantly reduced
      lipogenic activity and increased lipolytic activity in this tissue. Increased
      catabolism was also reflected in an acute increase in energy expenditure and
      glucose and fat oxidation in ob/ob mice treated with AOD-9401. In addition, AOD
      9401 increased in vitro lipolytic activity and decreased lipogenic activity in
      isolated adipose tissue from obese rodents and humans. Together, these findings
      indicate that oral administration of AOD-9401 alters lipid metabolism in adipose
      tissue, resulting in a reduction of weight gain in obese animals. The marked
      lipolytic and antilipogenic actions of AOD-9401 in human adipose tissues suggest
      that this small synthetic hGH peptide has potential in the treatment of human
      obesity.

PMID- 10950817
TI  - Glucose transporters and transport kinetics in retinoic acid-differentiated T47D
      human breast cancer cells.
AB  - The rates of glucose transport and of glycolysis and the expression of the
      glucose transporters GLUT-1 through GLUT-4 were measured in T47D human breast
      cancer cells that underwent differentiation by retinoic acid. Glucose transport
      was found to be the rate-limiting step of glycolysis in control and
      differentiated cells. The transporters GLUT-1, GLUT-3, and GLUT-4 were present in
      the cell membrane and in the cytoplasm, and GLUT-2 was present solely in the
      cytoplasm. Differentiation led to a reduction in GLUT-1 and to an increase in
      cytoplasmic GLUT-2 and GLUT-3 with no change in GLUT-4. Differentiation also
      caused a reduction in the maximal velocity of glucose transport by approximately
      40% without affecting the Michaelis-Menten constant of glucose transport. These
      changes did not alter the steady-state concentration of the phosphate metabolites
      regulating cell energetics but increased the content of phospholipid breakdown
      phosphodiesters. In conclusion, differentiation of human breast cancer cells
      appears to be associated with decreased glycolysis by a mechanism that involves a
      reduction in GLUT-1 and a slowdown of glucose transport.

PMID- 10950818
TI  - Overnight inhibition of insulin secretion restores pulsatility and
      proinsulin/insulin ratio in type 2 diabetes.
AB  - Impaired insulin secretion in type 2 diabetes is characterized by decreased first
      phase insulin secretion, an increased proinsulin-to-insulin molar ratio in
      plasma, abnormal pulsatile insulin release, and heightened disorderliness of
      insulin concentration profiles. In the present study, we tested the hypothesis
      that these abnormalities are at least partly reversed by a period of overnight
      suspension of beta-cell secretory activity achieved by somatostatin infusion.
      Eleven patients with type 2 diabetes were studied twice after a randomly ordered
      overnight infusion of either somatostatin or saline with the plasma glucose
      concentration clamped at approximately 8 mmol/l. Controls were studied twice
      after overnight saline infusions and then at a plasma glucose concentration of
      either 4 or 8 mmol/l. We report that in patients with type 2 diabetes, 1) as in
      nondiabetic humans, insulin is secreted in discrete insulin secretory bursts; 2)
      the frequency of pulsatile insulin secretion is normal; 3) the insulin pulse mass
      is diminished, leading to decreased insulin secretion, but this defect can be
      overcome acutely by beta-cell rest with somatostatin; 4) the reported loss of
      orderliness of insulin secretion, attenuated first-phase insulin secretion, and
      elevated proinsulin-to-insulin molar ratio also respond favorably to overnight
      inhibition by somatostatin. The results of these clinical experiments suggest the
      conclusion that multiple parameters of abnormal insulin secretion in patients
      with type 2 diabetes mechanistically reflect cellular depletion of immediately
      secretable insulin that can be overcome by beta-cell rest.

PMID- 10950819
TI  - Glucose transporter expression in human skeletal muscle fibers.
AB  - The present study was initiated to investigate GLUT-1 through -5 expression in
      developing and mature human skeletal muscle. To bypass the problems inherent in
      techniques using tissue homogenates, we applied an immunocytochemical approach,
      employing the sensitive enhanced tyramide signal amplification (TSA) technique to
      detect the localization of glucose transporter expression in human skeletal
      muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human
      muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in
      human skeletal muscle cells during gestation, but its expression is markedly
      reduced around birth and is further reduced to undetectable levels within the
      first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation
      and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in
      muscle cells throughout gestation, whereas after birth, the characteristic
      subcellular localization is as seen in adult muscle fibers. Our results show that
      GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth
      and development. GLUT-5 protein was undetectable in fetal and adult skeletal
      muscle fibers. In adult muscle fibers, only GLUT-4 was expressed at significant
      levels. GLUT-1 immunoreactivity was below the detection limit in muscle fibers,
      indicating that this glucose transporter is of minor importance for muscle
      glucose supply. Thus we hypothesize that GLUT-4 also mediates basal glucose
      transport in muscle fibers, possibly through constant exposure to tonal
      contraction and basal insulin levels.

PMID- 10950820
TI  - Resting energy expenditure-fat-free mass relationship: new insights provided by
      body composition modeling.
AB  - The relationship between resting energy expenditure (REE) and metabolically
      active fat-free mass (FFM) is a cornerstone in the study of physiological aspects
      of body weight regulation and human energy requirements. Important questions,
      however, remain unanswered regarding the observed linear REE-FFM association in
      adult humans. This led us to develop a series of REE-body composition models that
      provide insights into the widely used simple linear REE-FFM prediction model
      derived experimentally in adult humans. The new models suggest that the REE-FFM
      relationship in mammals as a whole is curvilinear, that a segment of this
      function within a FFM range characteristic of adult humans can be fit with a
      linear equation almost identical to that observed from a composite review of
      earlier human studies, and that mammals as a whole exhibit a decrease in the
      proportion of FFM as high metabolic rate organs with greater FFM. The present
      study thus provides a new approach for examining REE-FFM relationships, advances
      in a quantitative manner previously observed albeit incompletely formulated REE
      body composition associations, and identifies areas in need of additional
      research.

PMID- 10950821
TI  - Regulation of thyroid cell volumes and fluid transport: opposite effects of TSH
      and iodide on cultured cells.
AB  - Cell volume regulation by thyrotropin (TSH) and iodide, the main effectors
      involved in thyroid function, was studied in cultured thyroid cells. The mean
      cell volume, determined by performing 3-D reconstitution on confocal microscopy
      optical slices from living octadecylrhodamine-labeled cells cultured with both
      TSH and iodide (control cells), was 3.73 +/- 0.06 pl. The absence of iodide
      resulted in cell hypertrophy (136% of control value) and the absence of TSH in
      cell shrinkage (81%). These changes mainly affected the cell heights. The effect
      of TSH on cell volume was mediated by cAMP. The proportion of cytosolic volume (3
      O-methyl-D-glucose space vs. total volume) decreased in the absence of iodide
      (85% of control value) and increased in the absence of TSH (139%), whereas
      protein content showed the opposite changes (121 and 58%, respectively). The net
      apical-to-basal fluid transport was also inversely controlled by the two
      effectors. Iodide thus antagonizes TSH effects on cell volumes and fluid
      transport, probably via adenylylcyclase downregulation mechanisms. The absence of
      either iodide or TSH may mimic the imbalance occurring in pathological thyroids.

PMID- 10950822
TI  - Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin
      sensitivity in rat and human muscle.
AB  - Long-chain acyl-CoAs (LCACoA) are an activated lipid species that are key
      metabolites in lipid metabolism; they also have a role in the regulation of other
      cellular processes. However, few studies have linked LCACoA content in rat and
      human muscle to changes in nutritional status and insulin action. Fasting rats
      for 18 h significantly elevated the three major LCACoA species in muscle (P <
      0.001), whereas high-fat feeding of rats with a safflower oil (18:2) diet
      produced insulin resistance and increased total LCACoA content (P < 0.0001) by
      specifically increasing 18:2-CoA. The LCACoA content of red muscle from rats (4-8
      nmol/g) was 4- to 10-fold higher than adipose tissue (0.4-0.9 nmol/g, P < 0.001),
      suggesting that any contamination of muscle samples with adipocytes would
      contribute little to the LCACoA content of muscle. In humans, the LCACoA content
      of muscle correlated significantly with a measure of whole body insulin action in
      17 male subjects (r(2) = 0.34, P = 0.01), supporting a link between muscle lipid
      metabolism and insulin action. These results demonstrate that the LCACoA pool
      reflects lipid metabolism and nutritional state in muscle. We conclude that the
      LCACoA content of muscle provides a direct index of intracellular lipid
      metabolism and its links to insulin action, which, unlike triglyceride content,
      is not subject to contamination by closely associated adipose tissue.

PMID- 10950823
TI  - Palmitate oxidation rate and action on glycogen synthase in myoblasts from
      insulin-resistant subjects.
AB  - Elevated plasma lipid and nonesterified fatty acid concentrations reduce insulin
      mediated glucose disposal in skeletal muscle. Cultured myoblasts from 21 subjects
      were studied for rates of palmitate oxidation and the effect of palmitate on
      glycogen synthase activity at the end of an 18-h incubation in serum- and glucose
      free media. Oxidation rates of 40 microM palmitate in cultured myoblasts
      correlated with the fasting glucose (r = 0.71, P = 0.001), log fasting insulin (r
      = 0.52, P = 0.03), and insulin-mediated glucose storage rate (r = -0.50, P =
      0.04) of the muscle donors. Myoblast glycogen synthase activity can be regulated
      by 240 microM palmitate, but the changes are associated with the basal
      respiratory quotient and not with the insulin resistance of the muscle donor.
      These results indicate that myoblasts producing elevated palmitate oxidation
      rates in vitro can be used to identify skeletal muscle abnormalities which are
      primary contributors to insulin resistance in vivo. Effects of 240 microM
      palmitate on myoblast glycogen synthase activity appear to be mechanistically
      different from the relationship between myoblast palmitate oxidation rates and
      insulin resistance of the muscle donor.

PMID- 10950824
TI  - Transcriptional regulation of connective tissue growth factor by cortisol in
      osteoblasts.
AB  - Glucocorticoids have important effects on osteoblastic function. Connective
      tissue growth factor (CTGF)/insulin-like growth factor binding protein-related
      protein 2 (IGFBP-rP2) plays a role in cell adhesion and function. We examined the
      regulation of CTGF/IGFBP-rP2 synthesis in cultures of osteoblast-enriched cells
      from 22-day fetal rat calvariae (Ob cells). Cortisol caused a time- and dose
      dependent increase in CTGF/IGFBP-rP2 mRNA levels in Ob cells. Cycloheximide did
      not preclude the effect, indicating that it was not protein synthesis dependent.
      Cortisol increased the rate of CTGF/IGFBP-rP2 transcription and, in
      transcriptionally arrested Ob cells, did not modify the decay of the transcript.
      Parathyroid hormone decreased, whereas transforming growth factor-beta and, to a
      lesser extent, bone morphogenetic protein 2 increased CTGF/IGFBP-rP2 mRNA levels,
      but other hormones and growth factors had no effect. In conclusion, cortisol
      stimulates CTGF/IGFBP-rP2 transcription in Ob cells. Because CTGF/IGFBP-rP2 binds
      IGFs, its increased expression could be relevant to the actions of cortisol in
      bone.

PMID- 10950825
TI  - Effects of individual fatty acids on glucose uptake and glycogen synthesis in
      soleus muscle in vitro.
AB  - Soleus muscle strips from Wistar rats were preincubated with palmitate in vitro
      before the determination of insulin-mediated glucose metabolism in fatty acid
      free medium. Palmitate decreased insulin-stimulated glycogen synthesis to 51% of
      control in a time- (0-6 h) and concentration-dependent (0-2 mM) manner. Basal and
      insulin-stimulated glucose transport/phosphorylation also decreased with time,
      but the decrease occurred after the effect on glycogen synthesis. Preincubation
      with 1 mM palmitate, oleate, linoleate, or linolenate for 4 h impaired glycogen
      synthesis stimulated with a submaximal physiological insulin concentration (300
      microU/ml) to 50-60% of the control response, and this reduction was associated
      with impaired insulin-stimulated phosphorylation of protein kinase B (PKB).
      Preincubation with different fatty acids (all 1 mM for 4 h) had varying effects
      on insulin-stimulated glucose transport/phosphorylation, which was decreased by
      oleate and linoleate, whereas palmitate and linolenate had little effect. Across
      groups, the rates of glucose transport/phosphorylation correlated with the
      intramuscular long-chain acyl-CoA content. The similar effects of individual
      fatty acids on glycogen synthesis but different effects on insulin-stimulated
      glucose transport/phosphorylation provide evidence that lipids may interact with
      these two pathways via different mechanisms.

PMID- 10950826
TI  - Effect of exercise training on in vivo lipolysis in intra-abdominal adipose
      tissue in rats.
AB  - Intra-abdominal obesity is associated with cardiovascular disease and non-insulin
      dependent diabetes mellitus, and physical training has been suggested to
      alleviate these conditions. We compared epinephrine-stimulated lipolysis in vivo
      in three intra-abdominal adipose tissues (ATs: retroperitoneal, parametrial, and
      mesenteric) and in subcutaneous AT, and we also studied the effect of physical
      training. Moreover, we studied the effect of physical training on epinephrine
      stimulated lipolysis in muscle in vivo. Female rats were either swim trained (15
      wk, n = 8) or sedentary (n = 7). Under anesthesia, a two-stage intravenous
      epinephrine infusion (60 min of 80 and 200 ng. kg(-1). min(-1), respectively) was
      carried out, and local interstitial glycerol concentration was measured by the
      microdialysis technique. Blood flow was measured by microspheres. Training
      increased blood flow in all ATs [on average: 73 +/- 12 (trained) vs. 14 +/- 4
      (sedentary) ml. 100 g(-1). min(-1), P < 0. 05]; nevertheless, epinephrine
      stimulated interstitial glycerol concentrations were increased or unchanged.
      Interstitial glycerol concentration was higher in intra-abdominal than in
      subcutaneous AT in both trained and sedentary rats. In skeletal muscle,
      interstitial glycerol concentration and blood flow did not differ between trained
      and sedentary rats. In conclusion, in vivo lipolysis is higher both in the basal
      state and during epinephrine-stimulation in intra-abdominal than in subcutaneous
      AT, and training may be beneficial in alleviating intra-abdominal obesity by
      enhancing lipolysis in intra-abdominal fat depots.

PMID- 10950827
TI  - Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of
      HSL.
AB  - Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from
      the creosote bush, has been shown to decrease adipose tissue lipolytic activity
      both in vivo and in vitro. The present study was initiated to test the hypothesis
      that the decrease in lipolytic activity by masoprocol resulted from modulation of
      adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that
      oral administration of masoprocol to rats with fructose-induced
      hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P
      < 0.05), triglyceride (TG; P < 0.001), and insulin (P < 0.05) concentrations. In
      addition, isoproterenol-induced lipolytic rate and HSL activity were
      significantly lower (P < 0.001) in adipocytes isolated from masoprocol compared
      with vehicle-treated rats and was associated with a decrease in HSL protein.
      Incubation of masoprocol with adipocytes from chow-fed rats significantly
      inhibited isoproterenol-induced lipolytic activity and HSL activity, associated
      with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol
      had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity,
      but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the
      antilipolytic effect of masoprocol. The results of these in vitro and in vivo
      experiments suggest that the antilipolytic activity of masoprocol is secondary to
      its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase
      activity. As a consequence, masoprocol administration results in lower serum FFA
      and TG concentrations in hypertriglyceridemic rodents.

PMID- 10950828
TI  - Increased thermogenic response to food and fat oxidation in female athletes:
      relationship with VO(2 max).
AB  - The thermogenic response to food (TRF) and substrate oxidation were studied in 12
      endurance-trained and 13 untrained female subjects. Energy expenditure and
      substrate oxidation were calculated by indirect calorimetry before and for 6 h
      after an oral test meal and after the same meal given intragastrically on a
      separate occasion. The TRF was calculated after the oral meal, the obligatory
      component after the intragastric meal (OTRF), and the facultative component from
      the difference between the two. VO(2 max) was measured on a treadmill and body
      composition by underwater weighing. The TRF and OTRF were significantly higher in
      trained than in untrained subjects: 223 +/- 63 vs. 185 +/- 50 kJ/6 h (P < 0.03)
      and 174 +/- 38 vs. 131 +/- 37 kJ/6 h (P < 0.01) for the TRF and OTRF in trained
      vs. untrained subjects, respectively. Multiple regression analysis showed that
      maximum O(2) consumption (VO(2 max)), but not percentage of body fat, was
      significantly related to OTRF (r =0.68, P < 0.01). Trained subjects had higher
      fatty acid oxidation than untrained subjects before (0.6 vs. 0.4 mg. kg(-1). min(
      1), P < 0.05) and after the oral meal (13 +/- 6 vs. 8 +/- 4 g/6 h P < 0.05).
      These results demonstrate that 1) TRF is higher in trained than in untrained
      women; 2) this is due to a higher cost of nutrient digestion, absorption and
      storage; 3) the difference is related to higher VO(2 max); and 4) fatty acid
      oxidation is greater in trained women in both the postabsorptive and postprandial
      states. These observations suggest that endurance training induces metabolic
      changes that favor leanness.

PMID- 10950829
TI  - Role of glucose in the regulation of glutamine metabolism in health and in type 1
      insulin-dependent diabetes.
AB  - To determine the effect of glucose availability on glutamine metabolism,
      glutamine kinetics were assessed under conditions of hyperglycemia resulting from
      1) intravenous infusion of 7.5% dextrose in healthy adults and 2) insulin
      deficiency in young adults with insulin-dependent diabetes mellitus (IDDM). Eight
      healthy adults and five young adults with IDDM were studied in the postabsorptive
      state by use of a primed continuous infusion of D-[U-(14)C]glucose, L-[5,5,5
      (2)H(3)]leucine, and L-[3, 4-(13)C]glutamine. Whether resulting from insulin
      deficiency or dextrose infusion, the rise in plasma glucose was associated with
      increased glucose turnover (23.5 +/- 0.7 vs. 12.9 +/- 0.3 micromol. kg(-1). min(
      1), P < 0.01 and 20.9 +/- 2.5 vs. 12.8 +/- 0.4 micromol. kg(-1). min(-1), P =
      0.03, in health and IDDM, respectively). In both cases, high blood glucose failed
      to alter glutamine appearance rate (R(a)) into plasma [298 +/- 9 vs. 312 +/- 14
      micromol. kg(-1). h(-1), not significant (NS) and 309 +/- 23 vs 296 +/- 26
      micromol. kg(-1). h(-1), NS, in health and IDDM, respectively] and the estimated
      fraction of glutamine R(a) arising from de novo synthesis (210 +/- 7 vs. 217 +/-
      10 micromol. kg(-1). h(-1), NS and 210 +/- 16 vs. 207 +/- 21 micromol. kg(-1). h(
      1), NS, in health and IDDM, respectively). When compared with the euglycemic day,
      the apparent contribution of glucose to glutamine carbon skeleton increased when
      high plasma glucose resulted from intravenous dextrose infusion in healthy
      volunteers (10 +/- 0.8 vs. 4.8 +/- 0.3%, P < 0.01) but failed to do so when
      hyperglycemia resulted from insulin deficiency in IDDM. We conclude that 1) the
      contribution of glucose to the estimated rate of glutamine de novo synthesis does
      not increase when elevation of plasma glucose results from insulin deficiency,
      and 2) the transfer of carbon from glucose to glutamine may depend on insulin
      availability.

PMID- 10950830
TI  - A specific binding moiety for 1,25-dihydroxyvitamin D(3) in basal lateral
      membranes of carp enterocytes.
AB  - Carp (Cyprinus carpio), a freshwater fish that lives in a low-calcium
      environment, and Atlantic cod (Gadus morhua), a seawater fish that lives in a
      high-calcium environment, were studied for the presence of a novel membrane
      binding protein ("receptor") for the vitamin D metabolite, 1,25-dihydroxyvitamin
      D(3) [1,25(OH)(2)D(3)]. Basal lateral membranes from enterocytes of either
      species were prepared and analyzed for specific saturable binding. Membranes from
      carp revealed a dissociation constant of 1.23 nM with a maximal binding capacity
      of 212 fmol/mg protein. In comparison, membranes from Atlantic cod enterocytes
      revealed very low and nonsignificant levels of specific binding. The
      [(3)H]1,25(OH)(2)D(3) binding activity in carp was further characterized for
      protein dependence, detergent extractability, and competition for binding with
      the metabolites 25(OH)D(3) and 24R,25(OH)(2)D(3). Finally, introduction of
      1,25(OH)(2)D(3) to isolated carp enterocytes enhanced protein kinase C activity
      within 5 min, whereas intracellular Ca(2+) concentrations were unaffected by a
      range of 1,25(OH)(2)D(3) concentrations, as judged by fura 2 fluorescence. Thus
      the binding moiety may be a putative plasma membrane receptor for vitamin D,
      because it is functionally coupled to at least one signal transduction pathway.

PMID- 10950831
TI  - UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP
      activated protein kinase.
AB  - Uncoupling protein 3 (UCP-3), a member of the mitochondrial transporter
      superfamily, is expressed primarily in skeletal muscle where it may play a role
      in altering metabolic function under conditions of fuel depletion caused, for
      example, by fasting and exercise. Here, we show that treadmill running by rats
      rapidly (30 min) induces skeletal muscle UCP-3 mRNA expression (sevenfold after
      200 min), as do hypoxia and swimming in a comparably rapid and substantial
      fashion. The expression of the mitochondrial transporters, carnitine
      palmitoyltransferase 1 and the tricarboxylate carrier, is unaffected under these
      conditions. Hypoxia and exercise-mediated induction of UCP-3 mRNA result in a
      corresponding four- to sixfold increase in rat UCP-3 protein. We treated extensor
      digitorum longus (EDL) muscle with 5'-amino-4-imidazolecarboxamide ribonucleoside
      (AICAR), a compound that activates AMP-activated protein kinase (AMPK), an enzyme
      known to be stimulated during exercise and hypoxia. Incubation of rat EDL muscle
      in vitro for 30 min with 2 mM AICAR causes a threefold increase in UCP-3 mRNA and
      a 1.5-fold increase of UCP-3 protein compared with untreated muscle. These data
      are consistent with the notion that activation of AMPK, presumably as a result of
      fuel depletion, rapidly regulates UCP-3 gene expression.

PMID- 10950832
TI  - Inhibition of lipolysis causes suppression of endogenous glucose production
      independent of changes in insulin.
AB  - We have shown that insulin controls endogenous glucose production (EGP)
      indirectly, via suppression of adipocyte lipolysis. Free fatty acids (FFA) and
      EGP are suppressed proportionately, and when the decline in FFA is prevented
      during insulin infusion, suppression of EGP is also prevented. The present study
      tested the hypothesis that suppression of lipolysis under conditions of constant
      insulin would yield a suppression of EGP. N(6)-cyclohexyladenosine (CHA) was used
      to selectively suppress adipocyte lipolysis during euglycemic clamps in conscious
      male dogs. FFA suppression by CHA caused suppression of EGP. Liposyn control
      experiments, which maintained FFA levels above basal during CHA infusion,
      completely prevented the decline in EGP, whereas glycerol control experiments,
      which maintained glycerol levels close to basal, did not prevent a decline in
      EGP. These controls suggest that the EGP suppression was secondary to the
      suppression of FFA levels specifically. A difference in the sensitivity of FFA
      and EGP suppression (FFA were suppressed approximately 85% whereas EGP only
      declined approximately 40%) was possibly caused by confounding effects of CHA,
      including an increase in catecholamine and glucagons levels during CHA infusion.
      Thus suppression of lipolysis under constant insulin causes suppression of EGP,
      despite a significant rise in catecholamines.

PMID- 10950833
TI  - Glucagon response to exercise is critical for accelerated hepatic glutamine
      metabolism and nitrogen disposal.
AB  - The aim of this study was to determine the role of glucagon in hepatic glutamine
      (Gln) metabolism during exercise. Sampling (artery, portal vein, and hepatic
      vein) and infusion (vena cava) catheters and flow probes (portal vein, hepatic
      artery) were implanted in anesthetized dogs. At least 16 days after surgery, an
      experiment, consisting of a 120-min equilibration period, a 30-min basal sampling
      period, and a 150-min exercise period, was performed in these animals. [5
      (15)N]Gln was infused throughout experiments to measure gut and liver Gln
      kinetics and the incorporation of Gln amide nitrogen into urea. Somatostatin was
      infused throughout the study. Glucagon was infused at a basal rate until the
      beginning of exercise, when the rate was either 1) gradually increased to
      simulate the glucagon response to exercise (n = 5) or 2) unchanged to maintain
      basal glucagon (n = 5). Insulin was infused during the equilibration and basal
      periods at rates designed to achieve stable euglycemia. The insulin infusion was
      reduced in both protocols to simulate the exercise-induced insulin decrement.
      These studies show that the exercise-induced increase in glucagon is 1) essential
      for the increase in hepatic Gln uptake and fractional extraction, 2) required for
      the full increment in ureagenesis, 3) required for the specific transfer of the
      Gln amide nitrogen to urea, and 4) unrelated to the increase in gut fractional
      Gln extraction. These data show, by use of the physiological perturbation of
      exercise, that glucagon is a physiological regulator of hepatic Gln metabolism in
      vivo.

PMID- 10950834
TI  - Epidural blockade improves substrate utilization after surgery.
AB  - The purpose of this study was to test the hypothesis that epidural blockade with
      local anesthetic improves the anticatabolic effects of glucose after colorectal
      surgery. Sixteen patients were randomly assigned to undergo a 6-h stable isotope
      infusion study (3 h fasted, 3 h glucose infusion at 4 mg. kg(-1). min(-1)) on the
      second postoperative day with or without perioperative epidural blockade. Protein
      synthesis, breakdown and oxidation, and glucose production and clearance were
      assessed by L-[1-(13)C]leucine and [6, 6-(2)H(2)]glucose. Epidural blockade did
      not affect protein and glucose metabolism in the fasted state. Glucose infusion
      increased glucose clearance (P < 0.05), accompanied by an increase in the
      respiratory quotient (P < 0.05) and a decrease in leucine oxidation (P < 0.05)
      only in the presence of epidural blockade. An inverse correlation (r = -0.74, P <
      0.05) between changes in glucose clearance and leucine oxidation was observed. In
      conclusion, epidural blockade facilitates whole body glucose uptake and inhibits
      endogenous protein oxidation after abdominal surgery, indicating a shift from a
      protein to a more glucose-dominated substrate utilization.

PMID- 10950835
TI  - Functional parathyroid hormone receptors are present in an umbilical vein
      endothelial cell line.
AB  - Acute parathyroid hormone exposure induces vascular smooth muscle relaxation. In
      contrast, continuous infusion of parathyroid hormone leads to vasoconstriction
      and an elevation of blood pressure. Despite the known effects of parathyroid
      hormone on vascular smooth muscle, possible direct effects on the vascular
      endothelium have not previously been investigated. Using a human umbilical vein
      endothelial cell line, we found that parathyroid hormone increased both
      intracellular calcium and cellular cAMP content in these endothelial cells.
      Furthermore, exposure of these cells to increasing concentrations of parathyroid
      hormone stimulated both [(3)H]thymidine incorporation and endothelin-1 secretion.
      Parathyroid hormone/parathyroid hormone-related peptide receptor mRNA could be
      detected at low levels in these cells. In summary, these data demonstrate that
      endothelium-derived cells contain functional parathyroid hormone receptors. The
      potential physiological role of these receptors remains to be determined.

PMID- 10950836
TI  - Role of adrenoceptors and cAMP on the catecholamine-induced inhibition of
      proteolysis in rat skeletal muscle.
AB  - The role of adrenoceptor subtypes and of cAMP on rat skeletal muscle proteolysis
      was investigated using a preparation that maintains tissue glycogen stores and
      metabolic activity for several hours. In both soleus and extensor digitorum
      longus (EDL) muscles, proteolysis decreased by 15-20% in the presence of
      equimolar concentrations of epinephrine, isoproterenol, a nonselective beta
      agonist, or clenbuterol, a selective beta(2)-agonist. Norepinephrine also reduced
      proteolysis but less markedly than epinephrine. No change in proteolysis was
      observed when muscles were incubated with phenylephrine, a nonselective alpha
      agonist. The decrease in the rate of protein degradation induced by 10(-4) M
      epinephrine was prevented by 10(-5) M propranolol, a nonselective beta
      antagonist, and by 10(-5) M ICI 118.551, a selective beta(2)-antagonist. The
      antiproteolytic effect of epinephrine was not inhibited by prazosin or yohimbine
      (selective alpha(1)-and alpha(2)-antagonists, respectively) or by atenolol, a
      selective beta(1)-antagonist. Dibutyryl cAMP and isobutylmethylxanthine reduced
      proteolysis in both soleus and EDL muscles. The data suggest that catecholamines
      exert an inhibitory control of skeletal muscle proteolysis, probably mediated by
      beta(2)-adrenoceptors, with the participation of a cAMP-dependent pathway.

PMID- 10950837
TI  - A statistical model of the human core-temperature circadian rhythm.
AB  - We formulate a statistical model of the human core-temperature circadian rhythm
      in which the circadian signal is modeled as a van der Pol oscillator, the
      thermoregulatory response is represented as a first-order autoregressive process,
      and the evoked effect of activity is modeled with a function specific for each
      circadian protocol. The new model directly links differential equation-based
      simulation models and harmonic regression analysis methods and permits
      statistical analysis of both static and dynamical properties of the circadian
      pacemaker from experimental data. We estimate the model parameters by using
      numerically efficient maximum likelihood algorithms and analyze human core
      temperature data from forced desynchrony, free-run, and constant-routine
      protocols. By representing explicitly the dynamical effects of ambient light
      input to the human circadian pacemaker, the new model can estimate with high
      precision the correct intrinsic period of this oscillator ( approximately 24 h)
      from both free-run and forced desynchrony studies. Although the van der Pol model
      approximates well the dynamical features of the circadian pacemaker, the optimal
      dynamical model of the human biological clock may have a harmonic structure
      different from that of the van der Pol oscillator.

PMID- 10950838
TI  - Increased expression of GAD65 and GABA in pancreatic beta-cells impairs first
      phase insulin secretion.
AB  - The functional role of glutamate decarboxylase (GAD) and its product GABA in
      pancreatic islets has remained elusive. Mouse beta-cells express the larger
      isoform GAD67, whereas human islets express only the smaller isoform GAD65. We
      have generated two lines of transgenic mice expressing human GAD65 in pancreatic
      beta-cells (RIP7-hGAD65, Lines 1 and 2) to study the effect that GABA generated
      by this isoform has on islet cell function. The ascending order of hGAD65
      expression and/or activity in beta-cells was Line 1 heterozygotes < Line 2
      heterozygotes < Line 1 homozygotes. Line 1 heterozygotes have normal glucose
      tolerance, whereas Line 1 homozygotes and Line 2 heterozygotes exhibit impaired
      glucose tolerance and inhibition of insulin secretion in vivo in response to
      glucose. In addition, fasting levels of blood glucose are elevated and insulin is
      decreased in Line 1 homozygotes. Pancreas perfusion experiments suggest that GABA
      generated by GAD65 may function as a negative regulator of first-phase insulin
      secretion in response to glucose by affecting a step proximal to or at the
      K(ATP)(+) channel.

PMID- 10950839
TI  - Effect of CCK pretreatment on the CCK sensitivity of rat polymodal gastric vagal
      afferent in vitro.
AB  - To prevent the blood-borne interference and reflex actions via neighboring organs
      and the central nervous system, the study was conducted in an in vitro isolated
      stomach-gastric vagus nerve preparation obtained from overnight-fasted, urethan
      anesthetized rats. Afferent unit action potentials were recorded from the gastric
      branch of the vagus nerve. The left gastric artery was catheterized for intra
      arterial injection. In vitro we found that 1) 55/70 gastric vagal afferents
      (GVAs) were polymodal, responding to CCK-8 and mechanical stimuli, 13 were
      mechanoreceptive, and 2 were CCK-responsive; 2) sequential or randomized intra
      arterial injections of CCK-8 (0.1-200 pmol) dose-dependently increased firing
      rate and reached the peak rate at 100 pmol; 3) the action was suppressed by CCK-A
      (Devazepide) but not by CCK-B (L-365,260) receptor antagonist; 4) neither
      antagonist blocked the mechanosensitivity of GVA fibers. These results are
      consistent with corresponding in vivo well-documented findings. Histological data
      indicate that the layered structure of the stomach wall was preserved in vitro
      for 6-8 h. Based on these results, it seems reasonable to use the in vitro
      preparation for conducting a study that is usually difficult to be performed in
      vivo. For instance, because there was no blood supply in vitro, the composition
      of the interstitial fluid, i.e., the ambient nerve terminals, can be better
      controlled and influenced by intra-arterial injection of a defined solution. Here
      we report that acutely changing the ambient CCK level by a conditioning stimulus
      (a preceding intra-arterial injection of increasing doses of CCK-8) reduced the
      CCK sensitivity of GVA terminals to a subsequent test stimulus (a constant dose
      of CCK-8 intra-arterial injection).

PMID- 10950840
TI  - Liver export protein synthetic rates are increased by oral meal feeding in weight
      losing cancer patients.
AB  - We have demonstrated previously that, in the fasting state, whereas albumin
      synthesis is similar in cachectic cancer patients compared with controls,
      fibrinogen synthesis is increased. Whether synthesis of these proteins is altered
      after an oral meal was examined in eight weight-losing pancreatic cancer patients
      and six healthy controls by use of an intravenous flooding dose of [(2)H(5)]- or
      [(2)H(8)]phenylalanine. Cancer patients had a median weight loss of 19%, a
      significantly lower serum albumin concentration, and a significantly higher
      plasma fibrinogen concentration than controls (P < 0.005). Fasting albumin
      synthesis rates were similar between cancer patients and controls (median total
      synthesis rate 11.3 vs. 13.9 g/day, respectively) and rose on feeding by a
      similar degree (median 29 and 24%). The fasting fibrinogen total synthetic rate
      was significantly higher in cancer patients than in controls (median 3.3 vs. 1.0
      g/day, P = 0.0019). In cancer patients in the fed state, fibrinogen synthetic
      rate rose by a median of 38% (P = 0.012), whereas in controls there was no
      significant change. These findings demonstrate significant upregulation by
      feeding of acute-phase protein synthesis in cachectic cancer patients.

PMID- 10950841
TI  - Synthesis and identification of the quaternary ammonium-linked glucuronide of 1
      phenylimidazole in human liver microsomes and investigation of the human UDP
      glucuronosyltransferases involved.
AB  - 1-Phenylimidazole was investigated as a potential model substrate with respect to
      formation of a quaternary ammonium-linked glucuronide (N(+)-glucuronide) at an
      aromatic type tertiary amine. A reference sample of the potential N(+)
      glucuronide metabolite of 1-phenylimidazole was obtained by organic synthesis.
      The structural identity of the metabolite formed by incubation of 1
      phenylimidazole with human liver microsomes was proven to be the N(+)-glucuronide
      by exhibiting the same HPLC retention time and electrospray ionization mass
      spectrum as the reference sample. The screening of 1-phenylimidazole against a
      panel of nine expressed human UDP-glucuronosyltransferases indicated the
      involvement of UGT1A3 and UGT1A4 in the formation of the N(+)-glucuronide
      metabolite.

PMID- 10950842
TI  - Oxidation of the novel oxazolidinone antibiotic linezolid in human liver
      microsomes.
AB  - In vitro studies were conducted to identify the hepatic enzyme(s) responsible for
      the oxidative metabolism of linezolid. In human liver microsomes, linezolid was
      oxidized to a single metabolite, hydroxylinezolid (M1). Formation of M1 was
      determined to be dependent upon microsomal protein and NADPH. Over a
      concentration range of 2 to 700 microM, the rate of M1 formation conformed to
      first-order (nonsaturable) kinetics. Application of conventional in vitro
      techniques were unable to identify the molecular origin of M1 based on the
      following experiments: a) inhibitor/substrates for various cytochrome P-450 (CYP)
      enzymes were unable to inhibit M1 formation; b) formation of M1 did not correlate
      (r(2) < 0.23) with any of the measured catalytic activities across a population
      of human livers (n = 14); c) M1 formation was not detectable in incubations using
      microsomes prepared from a baculovirus insect cell line expressing CYPs 1A1, 1A2,
      2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5, and 4A11. In addition, results
      obtained from an in vitro P-450 inhibition screen revealed that linezolid was
      devoid of any inhibitory activity toward the following CYP enzymes (CYP1A2,
      CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). Additional in vitro studies
      excluded the possibility of flavin-containing monooxygenase and monoamine oxidase
      as potential enzymes responsible for metabolite formation. However, metabolite
      formation was found to be optimal under basic (pH 9.0) conditions, which suggests
      the potential involvement of either an uncharacterized P-450 enzyme or an
      alternative microsomal mediated oxidative pathway.

PMID- 10950843
TI  - Early events in the induction of rat hepatic UDP-glucuronosyltransferases,
      glutathione S-transferase, and microsomal epoxide hydrolase by 1,7
      phenanthroline: comparison with oltipraz, tert-butyl-4-hydroxyanisole, and tert
      butylhydroquinone.
AB  - Several classes of compounds are able to induce a spectrum of drug-metabolizing
      enzymes without inducing cytochrome P450s. Examples include antioxidants such as
      tert-butyl-4-hydroxyanisole and its metabolite tert-butylhydroquinone,
      dithiolthiones such as oltipraz, and N-heterocycles such as 1,7-phenanthroline.
      The events associated with induction of UDP-glucuronosyltransferases (UGT),
      glutathione S-transferases, and microsomal epoxide hydrolase after a single oral
      dose of these agents have been compared. No agent significantly elevated any of
      these enzyme activities within 24 h, but oltipraz and 1,7-phenanthroline
      significantly increased glutathione S-transferase and UGT activities by 48 h. 1,
      7-Phenanthroline and oltipraz showed generally similar time-course responses of
      drug-metabolizing enzyme mRNAs; little change from control at 6 h followed by
      significant and maximal increases 12 to 18 h after treatment. Maximal mRNA
      changes for 1,7-phenanthroline and oltipraz were of similar magnitude and
      clustered around 4-fold for most enzymes. With the exception of one UGT isozyme
      (UGT1A1), the elevations in mRNA were blocked by prior administration of
      actinomycin D, indicative of a transcription-dependent response. Neither tert
      butyl-4-hydroxyanisole nor tert-butylhydroquinone caused a statistically
      significant increase in any mRNA examined at any time point.

PMID- 10950844
TI  - O-Methylation of tea polyphenols catalyzed by human placental cytosolic catechol
      O-methyltransferase.
AB  - In the present study, we evaluated the metabolic O-methylation of several
      catechol-containing tea polyphenols by human placental catechol-O
      methyltransferase (COMT). (-)-Epicatechin, (+)-epicatechin, and (-)
      epigallocatechin were good substrates for metabolic O-methylation by placental
      cytosolic COMT (150-500 pmol/mg of protein/min), but (-)-epicatechin gallate and
      (-)-epigallocatechin gallate were O-methylated at much lower rates (<50 pmol/mg
      of protein/min). When (-)-epicatechin was used as substrate, its O-methylation by
      human placental COMT showed dependence on incubation time, cytosolic protein
      concentration, incubation pH, and concentration of S-adenosyl-L-methionine (the
      methyl donor). Analysis of cytosolic COMT from six human term placentas showed
      that the O-methylation of increasing concentrations of (-)-epicatechin or (-)
      epigallocatechin follows typical Michaelis-Menten kinetics, with K(m) and V(max)
      values of 2.2 to 8.2 microM and 132 to 495 pmol/mg of protein/min for (-)
      epicatechin and 3.9 to 6.7 microM and 152 to 310 pmol/mg of protein/min for (-)
      epigallocatechin, respectively. Additional analysis revealed that COMT-catalyzed
      O-methylation of (-)-epicatechin and (-)-epigallocatechin was strongly inhibited
      in a concentration-dependent manner by S-adenosyl-L-homocysteine (IC(50) = 3.2
      5.7 microM), a demethylated product of S-adenosyl-L-methionine. This inhibition
      by S-adenosyl-L-homocysteine follows a mixed (competitive plus noncompetitive)
      mechanism of enzyme inhibition. In summary, several catechol-containing tea
      polyphenols are rapidly O-methylated by human placental cytosolic COMT. This
      metabolic O-methylation is subject to strong inhibitory regulation by S-adenosyl
      L-homocysteine, which is formed in large quantities during the O-methylation of
      tea polyphenols.

PMID- 10950845
TI  - An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by
      metabolic intermediate complex formation.
AB  - An in vitro model is proposed to account for the clinically observed inhibition
      of cytochrome P450 (CYP) 3A that results from administration of clarithromycin,
      fluoxetine, or diltiazem. Rates for loss of CYP3A4 enzymatic activity resulting
      from metabolic intermediate complex formation and the concentration dependencies
      thereof were determined in vitro for clarithromycin, fluoxetine, and N-desmethyl
      diltiazem, which is the primary metabolite of diltiazem. Using the in vitro
      concentration-dependent rates for loss of activity, in vivo rates of CYP3A4
      inactivation were predicted for these compounds at a clinically relevant unbound
      plasma concentration of 0.1 microM. Based on the predicted rates combined with
      published rates for in vivo CYP3A degradation, our model predicts that
      fluoxetine, clarithromycin, and the primary metabolite of diltiazem reduce the
      steady-state concentration of liver CYP3A4 to approximately 72, 39, or 21% of
      initial levels, respectively. These reductions correspond to 1.4-, 2.6-, or 4.7
      fold increases, respectively, in the area under the plasma concentration-time
      curve of a coadministered drug that is eliminated exclusively by hepatic CYP3A4
      metabolism. These predicted results are in good agreement with reported clinical
      data. The major implication of this work is that fluoxetine, clarithromycin, and
      the primary metabolite of diltiazem, at clinically relevant concentrations,
      inactivate CYP3A4 enzymatic activity at rates sufficient to affect in vivo
      concentrations of CYP3A4 and thereby affect the clearance of compounds eliminated
      by this pathway. We speculate that mechanisms involving substrate-mediated
      mechanistic inactivation of CYPs play a major role in many clinically observed
      drug-drug interactions.

PMID- 10950846
TI  - Effect of aging on tryptophan hydroxylase in rat brain: implications on serotonin
      level.
AB  - Tryptophan hydroxylase (TrpH) catalyzes a rate-limiting step in the biogenesis of
      serotonin. The main objective of this study is to investigate the effect of aging
      on the activity of TrpH in serotonergic-enriched brain regions such as midbrain,
      pons, and medulla. TrpH activity was monitored by incubating various
      concentrations of tryptophan in a fixed amount of brain homogenate from midbrain,
      pons, and medulla of 2-month (young), 12-month (mature), and 24-month (old) rats
      (pH 7.4, 37 degrees C). The product 5-hydroxytryptophan was quantitated using a
      reversed phase HPLC equipped with an electrochemical detection system. Michaelis
      Menton constants, K(m) and V(max), were calculated using the Lineweaver-Burk
      plot. The affinity (K(m)) of the enzyme significantly declined in midbrain and
      pons of old rats (141.1 +/- 2. 6, 126.0 +/- 10.8 microM) relative to mature rats
      (22.4 +/- 7.7, 38. 2 +/- 4.7 microM). However, no change was observed in medulla
      of old rats. The V(max) of TrpH in pons of all three age group rats was fairly
      constant. However, the V(max) of midbrain was significantly elevated, whereas
      that of medulla was reduced in old rats relative to mature rats. Clearance
      formation, a ratio of V(max) to K(m), of 5-hydroxytryptophan declined
      significantly in midbrain, pons, and medulla of old rats relative to mature rats.
      A combined effect of inefficient phosphorylation and oxidative damage of TrpH
      enzyme may be responsible for lower TrpH activity in aging brain. Such
      alterations in TrpH activity may reduce the level of serotonin in brain, which
      may be linked to late-life depression and other brain disorders, such as
      Alzheimer and Parkinson diseases.

PMID- 10950847
TI  - Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine.
AB  - The metabolism of diclofenac to its 5-hydroxylated derivative in humans is
      catalyzed by cytochrome P450 (CYP)3A4. We report herein that in vitro this
      biotransformation pathway is stimulated by quinidine. When diclofenac was
      incubated with human liver microsomes in the presence of quinidine, the formation
      of 5-hydroxydiclofenac increased approximately 6-fold relative to controls.
      Similar phenomena were observed with diastereoisomers of quinidine, including
      quinine and the threo epimers, which produced an enhancement in the formation of
      5-hydroxydiclofenac in the order of 6- to 9-fold. This stimulation of diclofenac
      metabolism was diminished when human liver microsomes were pretreated with a
      monoclonal inhibitory antibody against CYP3A4. In contrast, neither cytochrome
      b(5) nor CYP oxidoreductase appeared to mediate the stimulation of diclofenac
      metabolism by quinidine, suggesting that the effect of quinidine is mediated
      through CYP3A4 protein. Further kinetic analyses indicated that V(max) values for
      the conversion of diclofenac to its 5-hydroxy derivative increased 4.5-fold from
      13.2 to 57.6 nmol/min/nmol of CYP with little change in K(m) (71-56 microM) over
      a quinidine concentration range of 0 to 30 microM. Conversely, the metabolism of
      quinidine was not affected by the presence of diclofenac; the K(m) value
      estimated for the formation of 3-hydroxyquinidine was approximately 1.5 microM,
      similar to the quinidine concentration required to produce 50% of the maximum
      stimulatory effect on diclofenac metabolism. It appears that the enhancement of
      diclofenac metabolism does not interfere with quinidine's access to the ferriheme
      oxygen complex, implicating the presence of both compounds in the active site of
      CYP3A4 at the same time. Finally, a approximately 4-fold increase in 5
      hydroxydiclofenac formation was observed in human hepatocyte suspensions
      containing diclofenac and quinidine, demonstrating that this type of drug-drug
      interaction occurs in intact cells.

PMID- 10950848
TI  - Catalysis of the 4-hydroxylation of retinoic acids by cyp3a7 in human fetal
      hepatic tissues.
AB  - Cytochrome P4503A7 (CYP3A7) is the primary CYP isoform expressed in human fetal
      hepatic microsomes, and its potential role in human embryotoxicity has attracted
      considerable investigative attention. In this study, we investigated the 4
      hydroxylation of highly embryotoxic and teratogenic retinoic acids (RA) as
      catalyzed by human fetal liver microsomes (HFLM) and demonstrated that CYP3A7 is
      an efficient RA hydroxylase. When all-trans-retinoic acid (tRA), 9-cis-retinoic
      acid (9cRA), or 13-cis-retinoic acid (13cRA) were incubated with HFLM (54-109
      gestational days) plus NADPH, each of these three retinoic acids was rapidly
      converted to its corresponding 4-hydroxy and 4-oxo metabolites. The reactions
      were strongly inhibited by CO (CO:O(2), 80:20) and were NADPH-dependent,
      indicating that the reactions were catalyzed by P450 isoenzymes. At 54 to 89
      gestational days, 4-hydroxylase activities were relatively low. However, at
      gestational days 96 to 109, activities were much higher. Selective inhibitors
      were employed for elucidation of the roles of individual CYP isoenzymes in HFLM.
      alpha-Naphthoflavone, paclitaxel, and diethyldithiocarbamate showed little or no
      effects on HFLM-catalyzed reactions, indicating that CYP1A1, CYP1A2, CYP1B1,
      CYP2C8, and CYP2E1 did not play significant roles in the catalysis. By contrast,
      troleandomycin strongly inhibited the reaction (70-75% inhibition), suggesting
      that CYP3A7 was primarily responsible for the observed catalysis. It was also
      discovered that CYP3A7 SUPERSOMES efficiently catalyzed the 4-hydroxylations of
      tRA, 9cRA, and 13cRA. Because 4-hydroxylated metabolites of RA are much less
      potent embryotoxins and teratogens, the results indicated that the 4
      hydroxylation of RA, catalyzed prenatally by CYP3A7, might play an important role
      in protecting the human fetus against RA-induced embryotoxicity.

PMID- 10950849
TI  - The disposition of saquinavir in normal and P-glycoprotein deficient mice, rats,
      and in cultured cells.
AB  - Protease inhibitors are very effective in treating patients infected with HIV.
      However, many drugs in this class penetrate poorly into the central nervous
      system (CNS) and may permit this site to be a sanctuary from which resistant
      virus can emerge. Previous studies have shown that the protease inhibitor
      saquinavir (SQV) interacts with the multidrug transport system, P-glycoprotein (P
      gp), expressed in epithelial cells in the gut mucosa and at the blood-brain
      barrier, and thus might affect both the oral absorption and the penetration of
      SQV into the CNS. To determine whether SQV is a substrate for P-gp, its uptake
      was determined in cancer cells, which do (Dx5) and do not (MES-SA) express P-gp.
      The distribution of SQV between brain tissue and plasma was also investigated in
      rats and in normal and P-gp-deficient mdr1a(-/-) mice. The distribution ratio of
      SQV in plasma:brain:cerebrospinal fluid was approximately 100:10:0.2 in rats. The
      accumulation of SQV was enhanced in MES-SA cells (P-gp-negative) versus Dx5 cells
      (P-gp-positive). Bolus i.v. injection of [(14)C]SQV (2 and 5 mg/kg) into mdr1a(-/
      ) and normal mice (n = 3 or 4) resulted in 3-fold higher radioactivity in brains
      from mdr1a(-/-) mice. Similarly, oral administration of [(14)C]SQV (500 mg/kg)
      resulted in a 5-fold increase in systemic exposure and a 10-fold increase in
      brain levels in mdr1a(-/-) mice. These data demonstrate that saquinavir is a
      substrate for P-gp and that this transport system may play a role in limiting
      oral absorption and CNS exposure to this protease inhibitor.

PMID- 10950850
TI  - A simple colorimetric assay for phenotyping the major human thermostable phenol
      sulfotransferase (SULT1A1) using platelet cytosols.
AB  - A thermostable phenol sulfotransferase, SULT1A1, has been implicated in numerous
      detoxification and bioactivation pathways; however, little is known regarding its
      endogenous function or its putative role in mediating risk for human
      environmental disease. A simple endpoint colorimetric assay is described that can
      be used for rapid phenotyping of SULT1A1 activity in human populations. The assay
      utilizes a microtiter-plate format and relatively small amounts of platelet
      cytosol-derived enzyme. The enzyme catalyzes the synthesis of 2-naphthylsulfate
      from 2-naphthol and 5'-phosphoadenosine 3'-phosphosulfate (PAPS), whereas
      addition of p-nitrophenyl sulfate to the assay contributes to an effective PAPS
      regenerating system. In contrast to other sulfotransferase assay methods, 3'
      phosphoadenosine 5'-phosphate (PAP) does not accumulate during the incubation to
      interfere with enzyme activity, but instead serves as a cofactor to cause the
      removal of sulfate from p-nitrophenyl sulfate to regenerate PAPS. This reaction
      concomitantly results in generation of p-nitrophenol that can be quantified
      colorimetrically at 405 nm (epsilon = 18,200 M(-1)) to give an indirect measure
      of sulfotransferase activity. Using platelet enzyme preparations from adult human
      subjects, sulfation rates of two prototypical thermostable phenol
      sulfotransferase substrates (2-naphthol and p-nitrophenol) and one thermolabile
      phenol sulfotransferase substrate (dopamine) were determined using standard
      radiochemical protocols. These data were then compared with results from the
      colorimetric assay using 2-naphthol as substrate. There was a good correlation
      between the phenotyping assay and radiochemical assays for both 2-naphthol
      sulfotransferase and p-nitrophenol sulfotransferase activity (r = 0.85 and 0.69,
      respectively). However, SULT1A1 activity was approximately 10 to 20 times higher
      with the colorimetric determination. As anticipated, there was no correlation
      between SULT1A1 activity and dopamine sulfotransferase activity (r = 0.07) in
      these human platelet preparations. This inexpensive and rapid method for
      phenotyping SULT1A1 activity may help investigators assess a role for this enzyme
      in disease susceptibility.

PMID- 10950852
TI  - Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in the
      human hepatoma cell line hep G2.
AB  - The UDP-glucuronosyltransferases (UGTs) have long been known to be inducible by
      various chemicals, including drugs, although the extent of induction in general
      has been modest. In the present study, we determined the ability of the dietary
      flavonoid chrysin to induce UGT activity, protein and mRNA. When pretreating
      human hepatoma Hep G2 cells with 25 microM chrysin, the glucuronidation of
      chrysin itself increased 4.2-fold when measured in the intact cell and 14-fold in
      the cell homogenate, i.e., autoinduction. Microsomes from chrysin-treated cells
      probed with specific antibodies in Western analyses showed marked induction of
      the UGT1A family of proteins. Isoform-specific induction of the important hepatic
      UGT1A1 protein was observed but not of UGT1A6 or UGT2B7. The strong induction of
      UGT1A1 was confirmed by Northern analyses of total RNA as well as mRNA, using a
      specific probe. UGT1A1 message as well as protein was detectable also in
      untreated Hep G2 cells. In catalytic activity assays with recombinant UGT1A1,
      1A4, 1A6 and 1A9, chrysin was found to be a high affinity substrate for UGT1A1
      (K(m) 0.35 microM). Catalytic activity was also found for UGT1A9 and 1A6 but not
      for 1A4. Further studies demonstrated a 20-fold induction of the glucuronidation
      of bilirubin by the chrysin-treated cells and a 7. 9-fold induction of the
      glucuronidation of the oral contraceptive drug ethinylestradiol, two of the best
      known and specific UGT1A1 substrates, demonstrating the potential importance of
      this induction. In view of these findings, it will be important to extend these
      studies to other dietary flavonoids.

PMID- 10950851
TI  - Metabolism of ezlopitant, a nonpeptidic substance P receptor antagonist, in liver
      microsomes: enzyme kinetics, cytochrome P450 isoform identity, and in vitro-in
      vivo correlation.
AB  - The enzyme kinetics of the metabolism of ezlopitant in liver microsomes from
      various species have been determined. The rank order of the species with regard
      to the in vitro intrinsic clearance of ezlopitant was monkey >> guinea pig > rat
      >> dog > human. CJ-12,764, a benzyl alcohol analog, was observed as a major
      metabolite, and a dehydrogenated metabolite (CJ-12,458) was equally important in
      human liver microsomes. Scale-up of the liver microsomal intrinsic clearance data
      and correcting for both serum protein binding and nonspecific microsomal binding
      yielded predicted hepatic clearance values that showed a good correlation with in
      vivo systemic blood clearance values. Including microsomal binding was necessary
      to achieve agreement between hepatic clearance values predicted from in vitro
      data and systemic clearance values measured in vivo. Cytochrome P450 (CYP) 3A4,
      3A5, and 2D6 demonstrated the ability to metabolize ezlopitant to CJ-12,458 and
      CJ-12,764. However, in liver microsomes, the CYP3A isoforms appear to play a
      substantially more important role in the metabolism of ezlopitant than CYP2D6, as
      assessed through the use of CYP-specific inhibitors, correlation to isoform
      specific marker substrate activities, and appropriate scale-up of enzyme kinetic
      data generated in microsomes containing individual heterologously expressed
      recombinant CYP isoforms. The apparent predominance of CYP3A over CYP2D6 is
      consistent with observations of the pharmacokinetics of ezlopitant in humans in
      vivo.

PMID- 10950853
TI  - Isoform specificity of N-deacetyl ketoconazole by human and rabbit flavin
      containing monooxygenases.
AB  - N-Deacetyl ketoconazole (DAK) is the major metabolite of orally administered
      ketoconazole. This major metabolite has been demonstrated to be further
      metabolized predominately by the flavin-containing monooxygenases (FMOs) to the
      secondary hydroxylamine, N-deacetyl-N-hydroxyketoconazole (N-hydroxy-DAK) by
      adult and postnatal rat hepatic microsomes. Our current investigation evaluated
      the FMO isoform specificity of DAK in a pyrophosphate buffer (pH 8.8) containing
      the glucose 6-phosphate NADPH-generating system. cDNA-expressed human FMOs (FMO1,
      FMO3, and FMO5) and cDNA-expressed rabbit FMOs (FMO1, FMO2, FMO3, and FMO5) were
      used to assess the metabolism of DAK to its subsequent FMO-mediated metabolites
      by HPLC analysis. Human and rabbit cDNA-expressed FMO3 resulted in extensive
      metabolism of DAK in 1 h (71.2 and 64.5%, respectively) to N-hydroxy-DAK (48.2
      and 47.7%, respectively) and two other metabolites, metabolite 1 (11.7 and 7.8%,
      respectively) and metabolite 3 (10.5 and 10.0%, respectively). Previous studies
      suggest that metabolite 1 is the nitrone formed after successive FMO-mediated
      metabolism of N-hydroxy-DAK. Moreover, these studies display similar metabolic
      profiles seen with adult and postnatal rat hepatic microsomes. The human and
      rabbit FMO1 metabolized DAK predominately to the N-hydroxy-DAK in 1 h (36.2 and
      25.3%, respectively) with minimal metabolism to the other metabolites (</=5%).
      Rabbit FMO2 metabolized DAK to N-hydroxy-DAK (15.9%) and metabolite 1 (6.6%).
      Last, DAK did not appear to be a substrate for human or rabbit FMO5. Heat
      inactivation of cDNA-expressed FMOs abolished DAK metabolite formation. These
      results suggest that DAK is a substrate for human and rabbit FMO1 and FMO3,
      rabbit FMO2, but not human or rabbit FMO5.

PMID- 10950854
TI  - Comparison of drug disposition between wild-type and novel tissue-type
      plasminogen activator pamiteplase in rats.
AB  - The pharmacokinetics of pamiteplase in rats was compared with the
      pharmacokinetics of recombinant wild-type tissue-type plasminogen activator (rwt
      PA). The half-life in the beta-phase and total clearance after administration of
      (125)I-labeled pamiteplase ((125)I-pamiteplase) to rats were 480 and 22% of those
      of (125)I-labeled rwt-PA ((125)I-rwt-PA), respectively. The amount of
      radioactivity distributed in the liver after administration of (125)I-pamiteplase
      was lower than that of (125)I-rwt-PA; consequently, a possible difference in
      metabolism between the drugs was assessed by an integration plot and a tissue
      sampling single-injection technique. Use of these two methods revealed that the
      hepatic clearances of both compounds accounted for almost all of the total
      clearance and also revealed that the hepatic clearance of (125)I-pamiteplase was
      markedly lower than that of (125)I-rwt-PA. Therefore, the lower distribution of
      pamiteplase in the liver compared with rwt-PA is thought to contribute greatly to
      the higher plasma concentration of pamiteplase. Additionally, the uptake of
      (125)I-pamiteplase in the liver was inhibited by rwt-PA, suggesting that there is
      a common uptake mechanism for both compounds.

PMID- 10950855
TI  - The 1'-hydroxylation of Rac-bufuralol by rat brain microsomes.
AB  - The 1'-hydroxylation of rac-bufuralol, which is catalyzed by polymorphic CYP2D6
      in humans, was studied in brain microsomes from male and female Wistar rats and
      from the female Dark Agouti rat, a model of the CYP2D6 poor metabolizer
      phenotype. The kinetics of the 1'-hydroxylation of bufuralol (1-1500 microM) by
      brain microsomes were biphasic. The activity of the high-affinity site of
      metabolism was consistent with Michaelis-Menten kinetics (apparent K(m1) = 0. 61
      1.42 microM, V(max1) = 4.3-4.8 fmol/min/mg of protein), whereas the low-affinity
      activity was better described by a Hill function (K(50%(2)) = 253-258 microM,
      V(max2) = 817-843 fmol/min/mg of protein, n = 1.2-1.3). Values for kinetic
      constants were similar in all rat strains. Quinine was only a weak inhibitor of
      both the high- (apparent K(i) = 90 microM) and low-affinity (210 microM) sites of
      metabolism. In contrast, the kinetics of 1'-hydroxylation of bufuralol by rat
      liver microsomes were best described by a two-site Michaelis-Menten function.
      V(max) values were 3 to 5 orders of magnitude greater compared with those for
      brain microsomes (male and female Wistar), and liver microsomes from female Dark
      Agouti rats were significantly less active than those from Wistar rats. These
      data, together with the known potent inhibitory effect of quinine on bufuralol 1'
      hydroxylation by rat liver microsomes, indicate tissue-specific differences in
      the enzymology of this reaction. The role of brain CYP2D enzymes remains to be
      clarified.

PMID- 10950856
TI  - Increased post-thaw viability and phase I and II biotransformation activity in
      cryopreserved rat liver slices after improvement of a fast-freezing method.
AB  - An existing cryopreservation method for liver slices applies 12%
      dimethylsulfoxide and rapid freezing. We found that cells in rat liver slices
      cryopreserved in this manner deteriorated rapidly upon culturing. To improve this
      cryopreservation method, we varied the dimethylsulfoxide concentration (0, 12,
      18, and 30%), the cryopreservation medium (Williams medium E, fetal calf serum,
      and University of Wisconsin medium), slice thickness, and the storage period at 4
      degrees C during slice preparation before cryopreservation. After thawing, slices
      were cultured for 4 h at 37 degrees C before their viability was evaluated by
      their potassium content and the number of intact cells determined
      histomorphologically. The biotransformation capacity of liver slices
      cryopreserved by the improved method was assessed by testosterone oxidation,
      hydroxycoumarin sulfation, and glucuronidation. Best results were obtained with
      18% dimethylsulfoxide in Williams medium E: the potassium content of
      cryopreserved slices was higher than 65%, and the number of intact cells was
      higher than 60% of that in fresh slices; with 12% dimethylsulfoxide, potassium
      content was less than 40%, and the number of intact cells was less than 30%.
      Results did not differ between the three cryopreservation media. Viability of
      thin slices (8-10 cell layers) was better maintained than that of thicker slices
      (>14 cell layers). Storage at 4 degrees C of slices before cryopreservation
      decreased viability after cryopreservation. Both oxidative and conjugation
      activities were better than 60% of fresh values. Although results varied, slices
      cryopreserved with this improved method and cultured for 4 h retained viability
      between 50 and 80%, and biotransformation activity between 60 and 90% of fresh
      slices.

PMID- 10950857
TI  - Immunoquantitation of FMO1 in human liver, kidney, and intestine.
AB  - To determine the level of FMO1 protein present in human liver tissues, a
      monospecific antibody was prepared and a sensitive Western blotting procedure
      with enhanced chemiluminescence detection was developed. Human FMO1, purified
      from insect cells expressing the recombinant protein, was used as a protein
      standard for absolute quantification. The average concentrations of FMO1 in
      microsomes prepared from human liver, kidney, intestine, and fetal liver were
      found to be <1, 47 +/- 9, 2.9 +/- 1.9, and 14.4 +/- 3.5 pmol/mg, respectively.
      Quantitation in intestinal microsomes was complicated by variable degrees of
      proteolytic degradation of FMO1, not seen in microsomes prepared from liver or
      kidney. Recombinant human FMO1 and detergent-solubilized human duodenal
      microsomes both metabolized p-tolyl methyl sulfide stereoselectively to the (R)
      sulfoxide, indicating the expression of functional FMO1 in human intestine. The
      relatively high levels of immunoquantifiable FMO1 in human kidney and fetal liver
      complement our previous catalytic studies in these tissues, which also
      demonstrated preferential (R)-p-tolyl methyl sulfoxide formation. These data
      demonstrate a profound ontogenic change in expression of hepatic FMO1 in humans,
      such that in adult life FMO1 is exclusively an extrahepatic drug-metabolizing
      enzyme. The marked expression levels of FMO1 found in human kidney coupled to the
      high catalytic activity of this isoform toward a diverse array of sulfides and
      tertiary amines suggest the possibility that human renal FMO1 is a significant
      contributor to the metabolic clearance of drugs and other xenobiotics bearing
      these functionalities.

PMID- 10950858
TI  - Role of reactive oxygen intermediates in the decrease of hepatic cytochrome P450
      activity by serum of humans and rabbits with an acute inflammatory reaction.
AB  - Serum of rabbits with a turpentine-induced acute inflammatory reaction
      (RS(INFLA)) and serum of humans with a viral infection (HS(INF)) were previously
      shown to diminish hepatic cytochrome P450 (P450) content and activity. To
      document the role of reactive oxygen intermediates in the serum-mediated decrease
      in P450 content and activity, hepatocytes of rabbits with an acute inflammatory
      reaction (H(INFLA)) were incubated with RS(INFLA) and HS(INF) for 4 h, and total
      P450 content (spectrally measurable P450), P450 activity (assessed by estimating
      the formation of theophylline metabolites), and amount of CYP1A1, CYP1A2, and
      CYP3A6 proteins were measured. RS(INFLA) or HS(INF) decreased P450 content and
      activity without affecting the amount of CYP1A1 and -1A2 H(INFLA). Exposure of
      H(CONT) or H(INFLA) to hydrogen peroxide (0.01-1.0 mM) and sodium nitroprusside
      (0.01-1.0 mM) produced a dose-dependent decrease in P450 content and in the
      formation of theophylline metabolites without modifying the amount of CYP1A1 and
      CYP1A2, whereas lipid peroxidation increased. Incubation of L-NAME (0.05-1.0 mM),
      dimethylthiourea (6.25-50 mM), or N-acetylcysteine (0.01-1.0 mM) with H(INFLA)
      partially prevented the decrease in P450 content and activity and the increased
      lipid peroxidation induced by RS(INFLA) and HS(INF). On the other hand, 3-amino
      1,2,4-triazole (10-100 mM) or diethyldithiocarbamate (1.0-10 mM) potentiated
      RS(INFLA)- and HS(INF)-mediated decreases in P450 content and activity and the
      increase in lipid peroxidation, without affecting the amount of CYP1A1 or -1A2;
      DL-buthionine-(S,R)-sulfoximine (2.5-25 mM) potentiated only the inhibition of
      1,3-dimethyluric acid formation. It is concluded that reactive oxygen
      intermediates are implicated in the decrease of H(INFLA) P450 content and
      activity induced by 4 h of exposure to RS(INFLA) or HS(INF).

PMID- 10950859
TI  - CYP3A4 is mainly responsibile for the metabolism of a new vinca alkaloid,
      vinorelbine, in human liver microsomes.
AB  - The metabolism of vinorelbine, a new anticancer agent belonging to the vinca
      alkaloid family, was investigated in human liver microsomes. Vinorelbine
      biotransformation consisted of one saturable and one nonsaturable process, and
      the K(m) and V(max) values for the saturable process were 1.90 microM and 25.3
      pmol/min/mg of protein, respectively. Several studies, including metabolism by
      cytochrome P450 (CYP) enzymes in a cDNA expression system and inhibition by
      specific antibodies and chemical inhibitors, showed that the main CYP enzyme
      involved in vinorelbine metabolism was CYP3A4. Also, the effects of vinorelbine
      on each of the CYP activities in human liver microsomes were investigated. High
      concentrations (100 microM) of vinorelbine inhibited CYP3A4 activity
      (testosterone 6beta-hydroxylation activity) by 45.2%. However, the inhibitory
      effects of vinorelbine on the other CYP activities were minimal. The 50%
      inhibitory concentration (IC(50)) of vinorelbine for testosterone 6beta
      hydroxylase was estimated to be 155 microM. The plasma concentration in patients
      is expected to be much lower than this value. These results indicate that
      vinorelbine metabolism is expected to be modulated by the drugs that are able to
      inhibit or induce CYP3A activity.

PMID- 10950860
TI  - Stereoselective metabolism of cibenzoline, an antiarrhythmic drug, by human and
      rat liver microsomes: possible involvement of CYP2D and CYP3A.
AB  - Stereoselective metabolism of cibenzoline succinate, an oral antiarrhythmic drug,
      was investigated on hepatic microsomes from humans and rats and microsomes from
      cells expressing human cytochrome P450s (CYPs). Four main metabolites, M1 (p
      hydroxycibenzoline), M2 (4,5-dehydrocibenzoline), and unknown metabolites M3 and
      M4, were formed by human and rat liver microsomes. The intrinsic clearance
      (CL(int)) of the M1 formation from R(+)-cibenzoline was 23-fold greater than that
      of S(-)-cibenzoline in human liver microsomes, whereas the R(+)/S(-)-enantiomer
      ratio of CL(int) for M2, M3, and M4 formation was 0.39 to 0.83. The total CL(int)
      for the formation of the four main metabolites from S(-)- and R(+)-cibenzoline
      was 1.47 and 1.64 microl/min/mg, respectively, suggesting that the total CL(int)
      in R(+)-enantiomer was slightly greater than that in S(-)-enantiomer in human
      liver microsomes. The M1 formation from R(+)-cibenzoline was highly correlated
      with bufuralol 1'-hydroxylation and CYP2D6 content and was inhibited by
      quinidine, a potent inhibitor of CYP2D6. Additionally, only microsomes containing
      recombinant CYP2D6 were capable of M1 formation. These results suggest that the
      M1 formation from R(+)-cibenzoline was catalyzed by CYP2D6. The formation of M2,
      M3, and M4 from S(-)- and R(+)-cibenzoline was highly correlated with
      testosterone 6beta-hydroxylation and CYP3A4 content. Ketoconazole, which is a
      potent inhibitor of CYP3A4/5, had a strong inhibitory effect on their formation,
      and the M4 formation from R(+)-cibenzoline was inhibited by quinidine by 45%. The
      formation of M2 was also inhibited by quinidine by 46 to 52% at lower cibenzoline
      enantiomers (5 microM), whereas the inhibition by quinidine was not observed at a
      higher substrate concentration (100 microM). In male rat liver microsomes,
      ketoconazole and quinidine inhibited the formation of the main metabolites, M1
      and M3, >74% and 44 to 59%, respectively. These results provide evidence that
      CYP3A and CYP2D play a major role in the stereoselective metabolism of
      cibenzoline in humans and male rats.

PMID- 10950862
TI  - HIF-1 and human disease: one highly involved factor.

PMID- 10950861
TI  - Electrophysiological analysis of the substrate selectivity of a sodium-coupled
      nucleoside transporter (rCNT1) expressed in Xenopus laevis oocytes.
AB  - Nucleoside transporters that mediate cellular uptake of therapeutic nucleoside
      analogs are major determinants of the pharmacokinetic properties of these
      compounds. Understanding the substrate selectivity of these transporters is
      critical in the development of therapeutic nucleoside analogs with optimal
      pharmacokinetic properties, including high oral bioavailability and tissue
      specific distribution. In general, substrate selectivity of nucleoside
      transporters has been evaluated indirectly by inhibition studies. The purpose of
      this study was to directly measure the transport of nucleoside analogs by the
      sodium-coupled pyrimidine-selective transporter rCNT1 using electrophysiology
      methods. We used a two-electrode voltage clamp assay to investigate the substrate
      selectivity of rCNT1; 19 structurally diverse nucleosides and nucleoside analogs
      were studied. Uridine-induced currents in voltage-clamped oocytes expressing
      rCNT1 were sodium-, voltage-, and concentration-dependent (K(0.5) = 21 microM),
      and were blocked by adenosine. Uridine-induced currents increased approximately 5
      fold upon hyperpolarization of membrane potential from -10 to -150 mV. Uridine,
      thymidine, and cytidine induced currents in rCNT1-expressing oocytes, whereas
      guanosine, inosine, and adenosine did not. Uridine, deoxyuridine, and cytidine
      analogs with modifications at the 3-, 4-, or 5-position were found to be
      substrates of rCNT1, whereas uridine and cytidine analogs modified at the 6
      position were not. In addition, it was found that the 5'-hydroxyl group of the
      sugar is not required for transport by rCNT1. These results enhance our
      understanding of the structural basis for substrate selectivity of nucleoside
      transporters and should prove useful in the development of therapeutic nucleoside
      analogs.

PMID- 10950863
TI  - Exploring the transcription-chromatin interface.

PMID- 10950864
TI  - The Dlk1 and Gtl2 genes are linked and reciprocally imprinted.
AB  - Genes subject to genomic imprinting exist in large chromosomal domains, probably
      reflecting coordinate regulation of the genes within a cluster. Such regulation
      has been demonstrated for the H19, Igf2, and Ins2 genes that share a bifunctional
      imprinting control region. We have identified the Dlk1 gene as a new imprinted
      gene that is paternally expressed. Furthermore, we show that Dlk1 is tightly
      linked to the maternally expressed Gtl2 gene. Dlk1 and Gtl2 are coexpressed and
      respond in a reciprocal manner to loss of DNA methylation. These genes are likely
      to represent a new example of coordinated imprinting of linked genes.

PMID- 10950865
TI  - Multiple RGS proteins alter neural G protein signaling to allow C. elegans to
      rapidly change behavior when fed.
AB  - Regulators of G protein signaling (RGS proteins) inhibit heterotrimeric G protein
      signaling by activating G protein GTPase activity. Many mammalian RGS proteins
      are expressed in the brain and can act in vitro on the neural G protein G(o), but
      the biological purpose of this multiplicity of regulators is not clear. We have
      analyzed all 13 RGS genes in Caenorhabditis elegans and found that three of them
      influence the aspect of egg-laying behavior controlled by G(o) signaling. A
      previously studied RGS protein, EGL-10, affects egg laying under all conditions
      tested. The other two RGS proteins, RGS-1 and RGS-2, act as G(o) GTPase
      activators in vitro but, unlike EGL-10, they do not strongly affect egg laying
      when worms are allowed to feed constantly. However, rgs-1; rgs-2 double mutants
      fail to rapidly induce egg-laying behavior when refed after starvation. Thus EGL
      10 sets baseline levels of signaling, while RGS-1 and RGS-2 appear to redundantly
      alter signaling to cause appropriate behavioral responses to food.

PMID- 10950866
TI  - PML is induced by oncogenic ras and promotes premature senescence.
AB  - Oncogenic ras provokes a senescent-like arrest in human diploid fibroblasts
      involving the Rb and p53 tumor suppressor pathways. To further characterize this
      response, we compared gene expression patterns between ras-arrested and quiescent
      IMR90 fibroblasts. One of the genes up-regulated during ras-induced arrest was
      promyelocytic leukemia (PML) protein, a potential tumor suppressor that encodes a
      component of nuclear structures known as promyelocytic oncogenic domains (PODs).
      PML levels increased during both ras-induced arrest and replicative senescence,
      leading to a dramatic increase in the size and number of PODs. Forced PML
      expression was sufficient to promote premature senescence. Like oncogenic ras,
      PML increased the levels of p16, hypophosphorylated Rb, phosphoserine-15 p53, and
      expression of p53 transcriptional targets. The fraction of Rb and p53 that
      colocalized with PML markedly increased during ras-induced arrest, and expression
      of PML alone forced p53 to the PODs. E1A abolished PML-induced arrest and
      prevented PML induction and p53 phosphorylation in response to oncogenic ras.
      These results imply that PML acts with Rb and p53 to promote ras-induced
      senescence and provide new insights into PML regulation and activity.

PMID- 10950867
TI  - A cell cycle-dependent protein serves as a template-specific translation
      initiation factor.
AB  - Cap-independent translation initiation on picornavirus mRNAs is mediated by an
      internal ribosomal entry site (IRES) in the 5' untranslated region (5' UTR) and
      requires both eukaryotic initiation factors (eIFs) and IRES-specific cellular
      trans-acting factors (ITAFs). We show here that the requirements for trans-acting
      factors differ between related picornavirus IRESs and can account for cell type
      specific differences in IRES function. The neurovirulence of Theiler's murine
      encephalomyelitis virus (TMEV; GDVII strain) was completely attenuated by
      substituting its IRES by that of foot-and-mouth disease virus (FMDV).
      Reconstitution of initiation using fully fractionated translation components
      indicated that 48S complex formation on both IRESs requires eIF2, eIF3, eIF4A,
      eIF4B, eIF4F, and the pyrimidine tract-binding protein (PTB) but that the FMDV
      IRES additionally requires ITAF(45), also known as murine proliferation
      associated protein (Mpp1), a proliferation-dependent protein that is not
      expressed in murine brain cells. ITAF(45) did not influence assembly of 48S
      complexes on the TMEV IRES. Specific binding sites for ITAF(45), PTB, and a
      complex of the eIF4G and eIF4A subunits of eIF4F were mapped onto the FMDV IRES,
      and the cooperative function of PTB and ITAF(45) in promoting stable binding of
      eIF4G/4A to the IRES was characterized by chemical and enzymatic footprinting.
      Our data indicate that PTB and ITAF(45) act as RNA chaperones that control the
      functional state of a particular IRES and that their cell-specific distribution
      may constitute a basis for cell-specific translational control of certain mRNAs.

PMID- 10950868
TI  - The checkpoint protein Ddc2, functionally related to S. pombe Rad26, interacts
      with Mec1 and is regulated by Mec1-dependent phosphorylation in budding yeast.
AB  - DDC2 is a novel component of the DNA integrity checkpoint pathway, which is
      required for proper checkpoint response to DNA damage and to incomplete DNA
      replication. Moreover, Ddc2 overproduction causes sensitivity to DNA-damaging
      agents and checkpoint defects. Ddc2 physically interacts with Mec1 and undergoes
      Mec1-dependent phosphorylation both in vitro and in vivo. The phosphorylation of
      Ddc2 takes place in late S phase and in G(2) phase during an unperturbed cell
      cycle and is further increased in response to DNA damage. Because Ddc2
      phosphorylation does not require any other known tested checkpoint factors but
      Mec1, the Ddc2-Mec1 complex might respond to the presence of some DNA structures
      independently of the other known checkpoint proteins. Our findings suggest that
      Ddc2 may be the functional homolog of Schizosaccharomyces pombe Rad26,
      strengthening the hypothesis that the mechanisms leading to checkpoint activation
      are conserved throughout evolution.

PMID- 10950869
TI  - tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c.
AB  - TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID,
      which translocates to mitochondria. Immunodepletion and gene disruption indicate
      BID is required for cytochrome c release. Surprisingly, the three-dimensional
      structure of this BH3 domain-only molecule revealed two hydrophobic alpha-helices
      suggesting tBID itself might be a pore-forming protein. Instead, we demonstrate
      that tBID functions as a membrane-targeted death ligand in which an intact BH3
      domain is required for cytochrome c release, but not for targeting. Bak-deficient
      mitochondria and blocking antibodies reveal tBID binds to its mitochondrial
      partner BAK to release cytochrome c, a process independent of permeability
      transition. Activated tBID results in an allosteric activation of BAK, inducing
      its intramembranous oligomerization into a proposed pore for cytochrome c efflux,
      integrating the pathway from death receptors to cell demise.

PMID- 10950870
TI  - Hypersensitivity to DNA damage leads to increased apoptosis during early mouse
      development.
AB  - Gastrulation in mice is associated with the start of extreme proliferation and
      differentiation. The potential cost to the embryo of a very rapid proliferation
      rate is a high production of damaged cells. We demonstrate a novel surveillance
      mechanism for the elimination of cells damaged by ionizing radiation during mouse
      gastrulation. During this restricted developmental window, the embryo becomes
      hypersensitive to DNA damage induced by low dose irradiation (<0.5 Gy) and
      undergoes apoptosis without cell cycle arrest. Intriguingly, embryonic cells,
      including germ cell progenitors, but not extraembryonic cells, become
      hypersensitive to genotoxic stress and undergo Atm- and p53-dependent apoptosis.
      Thus, hypersensitivity to apoptosis in the early mouse embryo is a cell fate
      dependent mechanism to ensure genomic integrity during a period of extreme
      proliferation and differentiation.

PMID- 10950871
TI  - Analysis of Arabidopsis glucose insensitive mutants, gin5 and gin6, reveals a
      central role of the plant hormone ABA in the regulation of plant vegetative
      development by sugar.
AB  - Sugars have signaling roles in a wide variety of developmental processes in
      plants. To elucidate the regulatory components that constitute the glucose
      signaling network governing plant growth and development, we have isolated and
      characterized two Arabidopsis glucose insensitive mutants, gin5 and gin6, based
      on a glucose-induced developmental arrest during early seedling morphogenesis.
      The T-DNA-tagged gin6 mutant abrogates the glucose-induced expression of a
      putative transcription factor, ABI4, previously shown to be involved in seed
      specific abscisic acid (ABA) responses. Thus, ABI4 might be a regulator involved
      in both glucose- and seed-specific ABA signaling. The characterization of the
      gin5 mutant, on the other hand, reveals that glucose-specific accumulation of ABA
      is essential for hexokinase-mediated glucose responses. Consistent with this
      result, we show that three ABA-deficient mutants (aba1-1, aba2-1, and aba3-2) are
      also glucose insensitive. Exogenous ABA can restore normal glucose responses in
      gin5 and aba mutants but not in gin6 plants. Surprisingly, only abi4 and abi5-1
      but not other ABA-insensitive signaling mutants (abi1-1, abi2-1, and abi3-1)
      exhibit glucose insensitivity, indicating the involvement of a distinct ABA
      signaling pathway in glucose responses. These results provide the first direct
      evidence to support a novel and central role of ABA in plant glucose responses
      mediated through glucose regulation of both ABA levels by GIN5 and ABA signaling
      by GIN6/ABI4.

PMID- 10950872
TI  - Defective processing of methylated single-stranded DNA by E. coli AlkB mutants.
AB  - Escherichia coli alkB mutants are very sensitive to DNA methylating agents.
      Despite these mutants being the subject of many studies, no DNA repair or other
      function has been assigned to the AlkB protein or to its human homolog. Here, we
      report that reactivation of methylmethanesulfonate (MMS)-treated single-stranded
      DNA phages, M13, f1, and G4, was decreased dramatically in alkB mutants. No such
      decrease occurred when using methylated lambda phage or M13 duplex DNA. These
      data show that alkB mutants have a marked defect in processing methylation damage
      in single-stranded DNA. Recombinant AlkB protein bound more efficiently to single
      than double-stranded DNA. The single-strand damage processed by AlkB was
      primarily cytotoxic and not mutagenic and was induced by SN2 methylating agents,
      MMS, DMS, and MeI but not by SN1 agent N-methyl-N-nitrosourea or by gamma
      irradiation. Strains lacking other DNA repair activities, alkA tag, xth nfo,
      uvrA, mutS, and umuC, were not defective in reactivation of methylated M13 phage
      and did not enhance the defect of an alkB mutant. A recA mutation caused a small
      but additive defect. Thus, AlkB functions in a novel pathway independent of these
      activities. We propose that AlkB acts on alkylated single-stranded DNA in
      replication forks or at transcribed regions. Consistent with this theory,
      stationary phase alkB cells were less MMS sensitive than rapidly growing cells.

PMID- 10950873
TI  - Chromatin fine structure profiles for a developmentally regulated gene:
      reorganization of the lysozyme locus before trans-activator binding and gene
      expression.
AB  - The chicken lysozyme locus is activated in a stepwise fashion during myeloid
      differentiation. We have used this locus as a model to study at high resolution
      changes in chromatin structure both in chicken cell lines representing various
      stages of macrophage differentiation and in primary cells from transgenic mice.
      In this study we have addressed the question of whether chromatin rearrangements
      can be detected in myeloid precursor cells at a stage well before overt
      transcription of the lysozyme gene begins. In addition to restriction enzyme
      accessibility assays and DMS footprinting, we have applied new, very sensitive
      techniques to assay for chromatin changes. Particularly informative was UV
      photofootprinting, using terminal transferase-dependent PCR and nonradioactive
      detection. We find that the basic chromatin structure in lysozyme nonexpressing
      hematopoietic precursor cells is highly similar to the pattern found in fully
      differentiated lysozyme-expressing cells. In addition, we find that only in
      nonexpressing cells are dimethylsulfate footprints and UV photofootprints
      affected by trichostatin, an inhibitor of histone deacetylation. These results
      are interpreted to mean that most chromatin pattern formation is complete before
      the binding of end-stage trans-activators, supporting the notion that heritable
      chromatin structure is central to the stable epigenetic programs that guide
      development.

PMID- 10950874
TI  - Immunolocalization of A1 adenosine receptors in mammalian spermatozoa.
AB  - The presence of A1 adenosine receptors (A1AR) in mammalian spermatozoa was
      previously demonstrated by radiochemical and immunochemical detection. This study
      was performed to investigate the cellular location of the A1AR to determine
      whether these receptors were somehow connected with ecto-adenosine deaminase and
      to evaluate their function in calcium uptake. By immunofluorescence staining we
      showed that in mammalian spermatozoa A1AR were constantly localized in the
      acrosomal region. This finding was confirmed by immunogold detection. Confocal
      analyses with anti-A1 and anti-ADA antibodies showed a high degree of co
      localization. Calcium loading assay showed that this association was functional
      and affected calcium accumulation in mammalian spermatozoa. Therefore, we
      concluded that the acrosomal localization of A1AR was a constant feature in
      mammalian sperm. Moreover, these A1 receptors were functionally coupled to ecto
      ADA and were able to modulate calcium uptake into an IP3-gated store.(J Histochem
      Cytochem 48:1163-1171, 2000)

PMID- 10950875
TI  - Vascular smooth muscle cells spontaneously adopt a skeletal muscle phenotype: a
      unique Myf5(-)/MyoD(+) myogenic program.
AB  - Smooth and skeletal muscle tissues are composed of distinct cell types that
      express related but distinct isoforms of the structural genes used for
      contraction. These two muscle cell types are also believed to have distinct
      embryological origins. Nevertheless, the phenomenon of a phenotypic switch from
      smooth to skeletal muscle has been demonstrated in several in vivo studies. This
      switch has been minimally analyzed at the cellular level, and the mechanism
      driving it is unknown. We used immunofluorescence and RT-PCR to demonstrate the
      expression of the skeletal muscle-specific regulatory genes MyoD and myogenin,
      and of several skeletal muscle-specific structural genes in cultures of the
      established rat smooth muscle cell lines PAC1, A10, and A7r5. The skeletal muscle
      regulatory gene Myf5 was not detected in these three cell lines. We further
      isolated clonal sublines from PAC1 cultures that homogeneously express smooth
      muscle characteristics at low density and undergo a coordinated increase in
      skeletal muscle-specific gene expression at high density. In some of these PAC1
      sublines, this process culminates in the high-frequency formation of myotubes. As
      in the PAC1 parental line, Myf5 was not expressed in the PAC1 sublines. We show
      that the PAC1 sublines that undergo a more robust transition into the skeletal
      muscle phenotype also express significantly higher levels of the insulin-like
      growth factor (IGF1 and IGF2) genes and of FGF receptor 4 (FGFR4) gene. Our
      results suggest that MyoD expression in itself is not a sufficient condition to
      promote a coordinated program of skeletal myogenesis in the smooth muscle cells.
      Insulin administered at a high concentration to PAC1 cell populations with a poor
      capacity to undergo skeletal muscle differentiation enhances the number of cells
      displaying the skeletal muscle differentiated phenotype. The findings raise the
      possibility that the IGF signaling system is involved in the phenotypic switch
      from smooth to skeletal muscle. The gene expression program described here can
      now be used to investigate the mechanisms that may underlie the propensity of
      certain smooth muscle cells to adopt a skeletal muscle identity.(J Histochem
      Cytochem 48:1173-1193, 2000)

PMID- 10950876
TI  - Calcyclin (S100A6) binding protein (CacyBP) is highly expressed in brain neurons.
AB  - The expression of a novel calcyclin (S100A6) binding protein (CacyBP) in
      different rat tissues was determined by Western and Northern blotting. Polyclonal
      antibodies against recombinant CacyBP purified from E. coli exhibited the highest
      reaction in the brain and weaker reaction in liver, spleen, and stomach. CacyBP
      immunoreactivity was also detected in lung and kidney. Densitometric analysis
      showed that the concentration of CacyBP in the soluble fractions of total brain
      and cerebellum is approximately 0.17 and 0. 34 ng/microg protein, respectively.
      Northern blotting with a specific cDNA probe confirmed the high level of CacyBP
      expression in the rat brain and lower levels in other tissues examined.
      Immunohistochemistry and in situ hybridization of rat brain sections revealed
      strong expression of CacyBP in neurons of the cerebellum, hippocampus, and
      cortex. The in situ hybridization detected CacyBP in hippocampus as early as P7
      (postnatal day 7) and a peak of expression at P21, and the expression signal was
      preserved until adulthood. In the entorhinal cortex, the peak of expression was
      observed at P7, whereas in the cerebellum it was seen at P21. The results
      presented here show that CacyBP is predominantly a neuronal protein. (J Histochem
      Cytochem 48:1195-1202)

PMID- 10950877
TI  - Gene expression of receptors for IL-6, LIF, and CNTF in regenerating skeletal
      muscles.
AB  - The biological actions of interleukin-6 (IL-6), leukemia inhibitory factor (LIF),
      and ciliary neurotrophic factor (CNTF) are mediated via respective functional
      receptor complexes consisting of a common signal-transducing component, gp130,
      and other specific receptor components, IL-6 receptor alpha (IL-6R), LIF receptor
      beta (LIFR), and CNTF receptor alpha (CNTFR). IL-6, LIF, and CNTF are implicated
      in skeletal muscle regeneration. However, the cell populations that express these
      receptor components in regenerating muscles are unknown. Using in situ
      hybridization histochemistry, we examined spatiotemporal expression patterns of
      gp130, IL-6R, LIFR, and CNTFR mRNAs in regenerating muscles after muscle
      contusion. At the early stages of regeneration (from 3 hr to Day 2 post
      contusion), significant signals for gp130 and LIFR mRNAs were detected in
      myonuclei and/or nuclei of muscle precursor cells (mpcs) and in mononuclear cells
      located in extracellular spaces between myofibers after muscle contusion, but IL
      6R mRNA was expressed only in mononuclear cells. At Day 7 post contusion, signals
      for gp130, LIFR, and IL-6R mRNAs were not detected in newly formed myotubes,
      whereas the CNTFR mRNA level was upregulated in myotubes. These findings suggest
      that the upregulation of receptor subunits in distinct cell populations plays an
      important role in the effective regeneration of both myofibers and motor neurons.
      (J Histochem Cytochem 48:1203-1213, 2000)

PMID- 10950878
TI  - CFTR, MDR1, and MRP1 immunolocalization in normal human nasal respiratory mucosa.
AB  - CFTR (cystic fibrosis transmembrane conductance regulator), MDR1 (multidrug
      resistance), and MRP1 (multidrug resistance-associated protein), members of the
      ABC transporter superfamily, possess multiple functions, particularly Cl(-),
      anion, and glutathione conjugate transport and cell detoxification. They are also
      hypothesized to have a number of complementary functions. It is generally
      accepted that data obtained from nasal mucosa can be extrapolated to lower airway
      cell physiology. The aim of the present study was to investigate by
      immunohistochemistry the differential localization of CFTR, MDR1, and MRP1 in the
      normal mucosa of 10 human nasal turbinates. In ciliated epithelial cells, CFTR
      was inconstantly expressed at the apical cell surface, intense membranous
      labeling was observed for MDR1, and intense cytoplasmic labeling was observed for
      MRP1. In the glands, a higher level of expression was observed on serous cells,
      at the apical surface (for CFTR), on lateral membranes (for MDR1), and with an
      intracytoplasmic distribution (for MRP1). In conclusion, CFTR, MDR1 and MRP1 are
      expressed in the epithelium and glands of the nasal respiratory mucosa, but with
      different patterns of expression. These results suggest major roles for CFTR,
      MDR1, and MRP1 in serous glandular cells and a protective function for MDR1 and
      MRP1 in respiratory ciliated cells. (J Histochem Cytochem 48:1215-1222, 2000)

PMID- 10950879
TI  - X-34, a fluorescent derivative of Congo red: a novel histochemical stain for
      Alzheimer's disease pathology.
AB  - X-34, a lipophilic, highly fluorescent derivative of Congo red, was examined as a
      histochemical stain for pathological changes in Alzheimer's disease (AD). X-34
      intensely stained neuritic and diffuse plaques, neurofibrillary tangles (NFTs),
      neuropil threads, and cerebrovascular amyloid. Comparison to standard methods of
      demonstrating AD pathology showed that X-34 correlated well with Bielschowsky and
      thioflavin-S staining. X-34 staining of NFTs correlated closely with anti-TAU
      antibody staining. A 1:1 correspondence of X-34 and anti-A beta antibody staining
      of plaques and cerebrovascular amyloid was observed. Both X-34 and thioflavin-S
      staining were eliminated by formic acid pretreatment, suggesting that beta-sheet
      secondary protein structure is a necessary determinant of staining. X-34 may be a
      general amyloid stain, like Congo red, because it also stains systemic amyloid
      deposits due to lambda-light chain monoclonal gammopathy. In conclusion, X-34 is
      a highly fluorescent marker for beta-sheet structures and intensely labels
      amyloid plaques, NFTs, neuropil threads, and vascular amyloid in AD brains. It
      can be used with both paraffin-embedded and frozen tissues as well as in
      combination with immunohistochemistry for double labeling. The intensity of
      staining and the simplicity and reproducibility of the technique suggest that it
      may be a useful addition to the standard techniques for evaluation of AD
      neuropathology. (J Histochem Cytochem 48:1223-1232, 2000)

PMID- 10950880
TI  - GFAP is expressed as a major soluble pool associated with glucagon secretory
      granules in A-cells of mouse pancreas.
AB  - To elucidate the role of intermediate filament proteins in endocrine cells, we
      investigated the expression and subcellular distribution of GFAP in mouse islets
      of Langerhans. For this purpose, combined immunocytochemical and biochemical
      analysis with a panel of antibodies was carried out to identify GFAP
      immunoreactive cells in mouse endocrine pancreas. Cell fractionation into NP-40
      soluble and detergent/high salt-insoluble components was performed to assess
      whether GFAP was located in the cytosolic and/or cytoskeletal compartments of
      immunoreactive cells. Immunoelectron microscopic analysis was carried out to
      determine the subcellular distribution of the protein. Peripheral islet cells
      were stained with anti-GFAP antiserum. These cells were identified as glucagon
      secreting cells by immunocytochemical staining of consecutive sections with anti
      somatostatin, anti-GFAP, and anti-glucagon antisera. Western blotting analysis of
      both NP-40-soluble and detergent/high-salt insoluble fractions of isolated islets
      of Langerhans allowed detection of GFAP in both cytosolic and cytoskeletal
      compartments. Interestingly, however, the former location was highly predominant.
      In addition, immunoelectron microscopy localized GFAP associated with the
      periphery of secretory granules. On the basis of these results, an intriguing
      role for GFAP in secretory events should be strongly suspected.(J Histochem
      Cytochem 48:1233-1242, 2000)

PMID- 10950881
TI  - Detection of immature dendritic cells in the enamel organ of rat incisors by
      using anti-cystatin C and anti-MHC class II immunocytochemistry.
AB  - Dendritic cells in the enamel organ of rat incisors were examined with
      immunocytochemistry using an anti-cystatin C antibody for immature dendritic
      cells and macrophages, OX6 for MHC Class II, ED1 for macrophages and dendritic
      cells, and ED2 for macrophages. Single cells positive for anti-cystatin C
      appeared in the enamel organ in zones at which ameloblasts secrete enamel matrix
      proteins. They were also present in transition and enamel maturation zones. In
      addition, ameloblasts, osteocytes, and osteoclasts were labeled by anti-cystatin
      C. ED1 and ED2 immunocytochemistry revealed that there was no macrophage
      population in the enamel organ of secretion, transition, or enamel maturation
      zone. A double labeling study showed that most anti-cystatin C-positive cells in
      the enamel maturation zone were also positive for OX6, whereas anti-cystatin C
      positive and OX6-negative cells were prevalent in the secretion zone. The results
      suggest that immature dendritic cells penetrate the enamel organ of the secretion
      zone and begin to mature in the zones of transition and enamel maturation. (J
      Histochem Cytochem 48:1243-1255, 2000)

PMID- 10950882
TI  - Tenascin expression and distribution in pleural inflammatory and fibrotic
      diseases.
AB  - We hypothesized that tenascin expression is increased in pleural inflammatory and
      fibrotic diseases and that its expression can be used as a marker of active
      pleural involvement. For this purpose we analyzed 71 histological samples of
      inflammatory and fibrotic pleura from patients with asbestos-induced pleural
      reaction (n = 6), postcardiac injury syndrome (n = 6), parapneumonic infection
      and/or empyema (n = 23), tuberculosis (n = 5, rheumatoid disease (n = 1), and
      fibrosis with inflammation of unknown etiology (n = 30). All 71 cases were
      studied by immunohistochemistry for tenascin. In 19 selected cases tenascin mRNA
      in situ hybridization was also performed. In every case, tenascin was increased
      by immunohistochemistry. Most prominent immunoreactivity was detected in areas of
      newly formed fibrosis. Increased tenascin mRNA expression by in situ
      hybridization was detected in the individual cells of the newly formed fibrosis
      underneath the fibrinous exudate. The tenascin mRNA-positive cells localized in
      areas in which by immunohistochemical studies the cells were positive for alpha
      smooth muscle actin, desmin, and vimentin, suggesting a myofibroblast phenotype.
      Tenascin mRNA expression was also seen less frequently in areas in which some
      cells were positive for cytokeratin. These cells might represent mesothelial
      cells entrapped in the inflammatory lesion. Alternatively, they might represent
      fibroblast-type cells with aberrant cytokeratin expression. We conclude that in
      pleural inflammatory and fibrotic diseases tenascin immunoreactivity is increased
      and tenascin mRNA-positive cells localized mainly in the areas of myofibroblast-
      and, less often, mesothelial-type cells, suggesting that mainly myofibroblasts
      and, less commonly, also mesothelial cells might be responsible for tenascin
      expression in pleural inflammatory and fibrotic diseases. (J Histochem Cytochem
      48:1257-1268, 2000)

PMID- 10950883
TI  - Quantitative immunogold localization of protein phosphatase 2B (calcineurin) in
      Paramecium cells.
AB  - For immunogold EM labeling analysis, we fixed Paramecium cells in 4% formaldehyde
      and 0.125% glutaraldehyde, followed by low-temperature embedding in unicryl and
      UV polymerization. We first quantified some obvious but thus far neglected side
      effects of section staining on immunogold labeling, using mono- or polyclonal
      antibodies (Abs) against defined secretory and cell surface components, followed
      by F(ab)(2)- or protein A-gold conjugates. Use of alkaline lead staining resulted
      in considerable rearrangement and loss of label unless sections were postfixed by
      glutaraldehyde after gold labeling. This artifact is specific for section
      staining with lead. It can be avoided by staining sections with aqueous uranyl
      acetate only to achieve high-resolution immunogold localization of a protein
      phosphatase on unicryl sections. In general, phosphatases are assumed to be
      closely, although loosely, associated with their targets. Because the occurrence
      of protein phosphatase 2B (calcineurin) in Paramecium has been previously
      established by biochemical and immunological work, as well as by molecular
      biology, we have used Abs against mammalian CaN or its subunits, CaN-A and CaN-B,
      for antigen mapping in these cells by quantitative immunogold labeling analysis.
      Using ABs against whole CaN, four structures are selectively labeled (with
      slightly decreasing intensity), i.e., infraciliary lattice (centrin-containing
      contractile cortical filament network), parasomal sacs (coated pits), and
      outlines of alveolar sacs (subplasmalemmal calcium stores, tightly attached to
      the cell membrane), as well as rims of chromatin-containing nuclear domains. In
      other subcellular regions, gold granules reached densities three to four times
      above background outside the cell but there was no selective enrichment, e.g., in
      cilia, ciliary basal bodies, cytosol, mitochondria, trichocysts (dense-core
      secretory organelles), and non-chromatin nuclear domains. Their labeling density
      was 4- to 8.5-fold (average 6.5-fold) less than that on selectively labeled
      structures. Labeling tendency was about the same with Abs against either subunit.
      Our findings may facilitate the examination of molecular targets contained in the
      selectively labeled structures. (J Histochem Cytochem 48:1269-1281, 2000)

PMID- 10950884
TI  - Ultrastructural and morphometric studies related to expression of the cell
      adhesion molecule PECAM-1/CD31 in developing rat lung.
AB  - It has recently been postulated that platelet/endothelial cell adhesion molecule
      1 (PECAM-1/CD31) might play a role in vascular tube formation. To evaluate the
      role of PECAM-1/CD31 in the formation of the capillary network in vivo, we
      conducted an ultrastructural immunohistochemical evaluation of the localization
      of PECAM-1/CD31 and its developmentally regulated expression in the periphery of
      the lungs of fetal, newborn, and adult rats. PECAM-1/CD31 was present mainly on
      luminal surfaces and at the junctions between endothelial cells. Moreover, in
      fetal lung, products of the immunoreaction were also found on the abluminal
      surfaces of endothelial cells. To relate those findings to the developmental
      changes in the capillary area of the lung, we performed a morphometric study of
      electronmicrographs. The cross-sectional area of blood vessels at the periphery
      of the lungs was significantly greater in 15-19-day-old fetuses than in
      postpartum animals (p<0.0001). Disappearance of the expression of PECAM-1/CD31 on
      the abluminal endothelial surface paralleled the changes in the cross-sectional
      area of blood vessels that occurred during the perinatal period. (J Histochem
      Cytochem 48:1283-1289, 2000)

PMID- 10950885
TI  - Journal impact factors for 1999

PMID- 10950886
TI  - Malignant mesothelioma: predictors of prognosis and clinical trials.

PMID- 10950887
TI  - Hypertension in patients with sleep apnoea, a combined effect?

PMID- 10950888
TI  - Smoking, lung function, and mortality.

PMID- 10950889
TI  - Prognostic factors for malignant mesothelioma in 142 patients: validation of
      CALGB and EORTC prognostic scoring systems.
AB  - BACKGROUND: The incidence of malignant mesothelioma is increasing. There is the
      perception that survival is worse in the UK than in other countries. However, it
      is important to compare survival in different series based on accurate prognostic
      data. The European Organisation for Research and Treatment of Cancer (EORTC) and
      the Cancer and Leukaemia Group B (CALGB) have recently published prognostic
      scoring systems. We have assessed the prognostic variables, validated the EORTC
      and CALGB prognostic groups, and evaluated survival in a series of 142 patients.
      METHODS: Case notes of 142 consecutive patients presenting in Leicester since
      1988 were reviewed. Univariate analysis of prognostic variables was performed
      using a Cox proportional hazards regression model. Statistically significant
      variables were analysed further in a forward, stepwise multivariate model. EORTC
      and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted,
      and survival rates were calculated from life tables. RESULTS: Significant poor
      prognostic factors in univariate analysis included male sex, older age, weight
      loss, chest pain, poor performance status, low haemoglobin, leukocytosis,
      thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic
      significance of cell type, haemoglobin, white cell count, performance status, and
      sex were retained in the multivariate model. Overall median survival was 5.9
      (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to
      28.7) and 3. 5% (0 to 8.5), respectively. Median, one, and two year survival data
      within prognostic groups in Leicester were equivalent to the EORTC and CALGB
      series. Survival curves were successfully stratified by the prognostic groups.
      CONCLUSIONS: This study validates the EORTC and CALGB prognostic scoring systems
      which should be used both in the assessment of survival data of series in
      different countries and in the stratification of patients into randomised
      clinical studies.

PMID- 10950890
TI  - Case-control study of 24 hour ambulatory blood pressure in patients with
      obstructive sleep apnoea and normal matched control subjects.
AB  - BACKGROUND: There is considerable debate regarding the relationship between
      obstructive sleep apnoea (OSA) and hypertension. It is unclear whether OSA is an
      independent vascular risk factor as studies attempting to assess this association
      have produced conflicting results because of confounding variables such as upper
      body obesity, alcohol, and smoking. A case-control study of 24 hour ambulatory
      blood pressure was undertaken in patients with OSA and matched controls to assess
      whether OSA is an independent correlate of diurnal hypertension. METHODS: Forty
      five patients with moderate to severe OSA and excessive daytime sleepiness were
      matched with 45 controls without OSA in a sleep study. Matched variables included
      age, body mass index (BMI), alcohol, cigarette usage, treated hypertension, and
      ischaemic heart disease. Upper body obesity was compared by waist:hip and
      waist:height ratios; 24 hour ambulatory blood pressure recordings were performed
      (before treatment for OSA) in all subjects. RESULTS: Patients with OSA had
      significantly increased mean (SD) diastolic blood pressure (mm Hg) during both
      daytime (87.4 (10.2) versus 82.8 (9.1); p=0.03, mean difference 4.6 (95% CI 0.7
      to 8.6) and night time (78.6 (9.3) versus 71.4 (8.0); p<0.001, mean difference
      7.2 (95% CI 3.7 to 10.6)), and higher systolic blood pressure at night (119.4
      (20.7) versus 110.2 (13.9); p=0.01, mean difference 9.2 (95% CI 2.3 to 16.1)).
      The nocturnal reduction in blood pressure ("dipping") was smaller in patients
      with OSA than in control subjects. CONCLUSIONS: Compared with closely matched
      control subjects, patients with OSA have increased ambulatory diastolic blood
      pressure during both day and night, and increased systolic blood pressure at
      night. The magnitude of these differences is sufficient to carry an increased
      risk of cardiovascular morbidity. The slight excess of upper body fat deposition
      in the controls may make these results conservative.

PMID- 10950891
TI  - Comparison of two in-laboratory titration methods to determine effective pressure
      levels in patients with obstructive sleep apnoea.
AB  - BACKGROUND: Treatment of the sleep apnoea/hypopnoea syndrome with nasal
      continuous positive airway pressure (CPAP) conventionally requires a titration
      procedure in a sleep laboratory. The upper airway has a hysteresis phenomenon
      which accounts for a decrease in the effective positive pressure level once an
      initial effective pressure setting has been reached. The aim of this study was to
      quantify the difference in the initial and final effective pressure settings when
      the titration sleep study takes into account these possible changes in the
      effective pressure level. METHODS: Eighty five patients completed the study.
      During a titration sleep study the pressure was increased by 1 cm H2O in a
      stepwise fashion until obstructive respiratory events disappeared (effective
      pressure 1, Peff(1)). The pressure level was then decreased by increments of 1 cm
      H2O until breathing abnormalities reappeared. At this time pressure was re
      increased by increments of 1 cm H(2)O to normalise breathing (Peff(2)). RESULTS:
      The mean (SD) value of Peff(1) was 9.5 (2.6) cm H2O. The pressure was then
      reduced during 0.5 (0.6) hours to reach the minimal pressure (7.0 (2.0) cm H2O).
      The pressure obtained after a downward titration had to be re-increased in 79
      patients, the Peff(2) level being significantly lower than Peff(1) (8.9 (2.8) cm
      H2O, p = 0.0002), mean difference 0.6 (1.5) cm H2O (95% confidence interval 0.29
      to 0.93). CONCLUSION: Attempts to decrease the positive pressure level during
      conventional determination of the effective pressure level allow a significant
      decrease in the pressure setting. This should be taken into account in each
      patient who requires an in-laboratory manual CPAP titration procedure.

PMID- 10950892
TI  - Pulmonary function, smoking cessation and 30 year mortality in middle aged
      Finnish men.
AB  - BACKGROUND: Although it is well known that impaired pulmonary function is a
      strong predictor of mortality and that smoking decreases pulmonary function,
      little is known about the long term effect of smoking cessation on mortality at
      different levels of pulmonary function. We have studied the impact of smoking
      cessation on mortality over the entire range of baseline pulmonary function.
      METHODS: The study subjects consisted of men aged 40-59 at entry who were the
      Finnish participants in the Seven Countries Study during 1959-89. RESULTS: In all
      the participants (n = 1582) impaired forced expiratory volume in 0.75 seconds
      (FEV(0.75)) was significantly associated with increased all cause mortality. When
      those who gave up smoking during the follow up period were compared with
      continuous smokers (n = 860) all cause mortality was found to be decreased among
      those who quit. The relative adjusted hazard (HR) was 0.71 (95% confidence
      interval 0.50 to 1.00). The median survival time in those who stopped smoking
      compared with those who continued to smoke from 1969 onwards was 7.65, 7.59, and
      6.30 years longer in the lowest, middle and highest tertiles of adjusted
      FEV(0.75) distribution, respectively. In those who gave up smoking, mortality
      from cardiovascular causes was significantly lower (HR 0.60 (95% CI 0.37 to
      0.98)). CONCLUSIONS: These findings suggest that smokers across the entire range
      of pulmonary function may increase their expectation of lifespan by giving up
      smoking.

PMID- 10950893
TI  - Epidemiology of familial sarcoidosis in the UK.
AB  - BACKGROUND: The last comprehensive epidemiological studies on familial
      sarcoidosis in the UK were more than 25 years ago, reporting another affected
      family member in 1.7% of index cases. A significant proportion of like-sex over
      unlike-sex pairs, an excess of mother-child over father-child associations, and a
      preponderance of monozygous over dizygous twins was noted. Another study reported
      ethnic heterogeneity in familial disease. This study was undertaken to identify
      the risk ratio (lambda(S)) for siblings of familial sarcoidosis in the UK, to
      determine if the previous epidemiological findings have persisted, and to
      reassess whether ethnic heterogeneity prevails in familial disease. METHOD:
      Questionnaires were sent to 406 index patients. RESULTS: Two hundred and sixty
      eight replies (66%) were received. Twenty four of the original 406 index patients
      (5.91%) were found to have at least one other relative (first, second or third
      degree) with biopsy proven sarcoidosis. A lambda(S) value of 36-73 was calculated
      indicating significant familial clustering of the disease. Ethnically the
      families comprised 62.5% Caucasian, 29.2% Afro-Caribbean, and 8.3% Asian. Mean
      age at diagnosis was 39.8 years for women and 40.9 years for men with a male to
      female ratio of 1:1.7. This differed for the Asian families in which all the
      affected members were male. Three sets of female twins (two monozygous and one
      dizygous) were included. There was an equal distribution of like-sex (primarily
      female) and unlike-sex families as well as mother-child and father-child pairs.
      Pulmonary involvement was predominant irrespective of ethnicity, as was the need
      for corticosteroid treatment. CONCLUSIONS: These results support the theory that
      a shared determinant (either genetic or environmental) is operating in familial
      sarcoidosis and suggest that this determinant is similar for all ethnic groups.

PMID- 10950894
TI  - Expression of thioredoxin in granulomas of sarcoidosis: possible role in the
      development of T lymphocyte activation.
AB  - BACKGROUND: Activated T lymphocytes are one of the characteristic features of
      sarcoidosis. The mechanism of T cell activation, expressing various activation
      markers including interleukin 2 receptor (IL-2R), has been extensively
      investigated but the precise mechanism remains unknown. Although thioredoxin
      (TRX) displays a number of biological activities including IL-2R inducing
      activity, its role in the induction of IL-2R expression on T cells in sarcoidosis
      has not been determined. The expression of TRX and IL-2R in granulomas of
      patients with sarcoidosis has been studied to clarify a possible role for TRX in
      the induction of IL-2R expression. METHODS: Granulomas in specimens of lung
      tissue and lymph nodes from five patients with sarcoidosis were
      immunohistochemically stained with anti-TRX antibody and anti-IL-2Ralpha chain
      antibody and the concentration of TRX in the bronchoalveolar lavage (BAL) fluid
      from 20 patients with pulmonary sarcoidosis was measured. RESULTS: Granulomas in
      lung and lymph node tissue from patients with sarcoidosis showed strong
      reactivity with anti-TRX antibody. Positive staining was present in the
      macrophages, epithelioid cells, and Langhans' type giant cells but not in
      lymphocytes. IL-2R was expressed on lymphocytes in the same granulomas. By
      contrast, positive immunoreactivity was not found in lung tissue specimens from
      12 control subjects. Concentrations of TRX in BAL fluid were higher in patients
      with pulmonary sarcoidosis (median (range) 122.6 (20.9-303.3) ng/ml) than in
      control subjects (32.9 (16.8-52.8) ng/ml, p<0.05). CONCLUSIONS: TRX is highly
      expressed and is locally produced by granulomas in patients with sarcoidosis. The
      coexistence of immunoreactive TRX and IL-2R in the same granulomas suggests that
      TRX might act as a local inducing factor for IL-2R expression on T cells.

PMID- 10950896
TI  - Induced sputum in children: feasibility, repeatability, and relation of findings
      to asthma severity.
AB  - BACKGROUND: The collection of induced sputum provides a non-invasive method of
      investigating airway inflammation. Few studies have been performed in children,
      so a study was undertaken to determine the feasibility of sputum induction, the
      repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP)
      levels, and the relation of these to current asthma severity. For comparison,
      serum ECP levels were also measured. METHODS: In a cross sectional study of
      children aged 5-15 years, 27 healthy children and 60 with asthma underwent sputum
      induction using inhaled nebulised hypertonic saline. The whole sputum sample was
      used for analysis. Ten children with stable asthma repeated the procedure within
      10 days. RESULTS: A satisfactory sample (>500 non-squamous cells) was obtained in
      61% of children with asthma and in 60% of healthy controls. The limits of
      agreement within subjects ranged from a 0.68 to 2.8 fold difference for
      eosinophil differential counts and from 0.38 to 4.4 fold for sputum ECP. Despite
      a median of 42% squamous cells, significant differences were found between asthma
      and healthy controls for the eosinophil differential count (p = 0.0004), total
      eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there
      was no correlation between any marker of airway inflammation and asthma severity,
      however expressed, including lung function. CONCLUSIONS: Sputum induction is only
      possible in a proportion of children. The repeatability of sputum cell counts and
      ECP levels, measured in a small number of children, was similar to that reported
      in adults. Sputum analysis revealed no evidence of airway inflammation in a
      number of highly symptomatic children with asthma.

PMID- 10950895
TI  - Asthma exacerbations during long term beta agonist use: influence of beta(2)
      adrenoceptor polymorphism.
AB  - BACKGROUND: Polymorphisms of the beta(2) adrenoceptor influence receptor function
      in vitro and asthma phenotypes in vivo. However, their importance in determining
      responses to inhaled beta agonist treatment has not been clearly defined.
      METHODS: In a retrospective analysis of previously published data we have
      examined relationships between polymorphisms at codons 16 and 27 of the beta(2)
      adrenoceptor and clinical outcomes in a randomised, placebo controlled, crossover
      trial of regularly scheduled salbutamol and salmeterol in 115 patients with mild
      to moderate asthma. Genotyping was obtained for positions 16 and 27 in 108 and
      107 patients, respectively. For position 16, 17 patients (16%) were homozygous
      Arg-Arg, 40 (37%) were heterozygous Arg-Gly, and 51 (47%) were homozygous Gly
      Gly. RESULTS: Within the homozygous Arg-16 group major exacerbations were more
      frequent during salbutamol treatment than with placebo (1.91 (95% CI 1.07 to
      3.12) per year versus 0.81 (95% CI 0.28 to 1.66) per year; p = 0.005). No
      significant treatment related differences occurred for heterozygous Arg-Gly
      patients (salbutamol 0.11 (95% CI 0.01 to 0.40), placebo 0.54 (95% CI 0.26 to
      1.00) exacerbations per year) or homozygous Gly-16 patients (salbutamol 0.38 (95%
      CI 0.17 to 0.73), placebo 0.30 (95% CI 0.12 to 0.61) exacerbations per year). No
      adverse changes occurred for any position 16 subgroup with salmeterol. There was
      no significant relationship between position 27 genotypes and treatment related
      outcomes. CONCLUSION: Homozygous Arg-16 patients are susceptible to clinically
      important increases in asthma exacerbations during chronic dosing with the short
      acting beta(2) agonist salbutamol.

PMID- 10950897
TI  - Diet and childhood asthma in a society in transition: a study in urban and rural
      Saudi Arabia.
AB  - BACKGROUND: The causes of the worldwide increases in asthma and allergic diseases
      in childhood, which seem to relate to increasing prosperity, are unknown. We have
      previously hypothesised that a reduction in the antioxidant component of the diet
      is an important factor. An investigation was undertaken of dietary and other risk
      factors for asthma in Saudi Arabia where major lifestyle differences and
      prevalences of allergic disease are found in different communities. METHODS: From
      a cross sectional study of 1444 children with a mean age of 12 (SD 1) years in
      Jeddah and a group of rural Saudi villages, we selected 114 cases with a history
      of asthma and wheeze in the last 12 months and 202 controls who had never
      complained of wheeze or asthma, as recorded on the ISAAC questionnaire. Risk
      factors for asthma and allergies (family history, social class, infections,
      immunisations, family size, and diet) were ascertained by questionnaire. Atopy
      was assessed by skin prick testing. RESULTS: In univariate analyses, family
      history, atopy, and eating at fast food outlets were significant risk factors for
      wheezy illness, as were the lowest intakes of milk and vegetables and of fibre,
      vitamin E, calcium, magnesium, sodium, and potassium. These differences were
      present also in the urban children considered separately. Sex, family size,
      social class, infections, and parental smoking showed no relationship to risk. In
      multiple logistic regression analysis, urban residence, positive skin tests,
      family history of allergic disease, and the lowest intakes of vitamin E,
      magnesium and sodium related significantly and independently to risk. The lowest
      tertile of intake of vitamin E was associated with a threefold (95% CI 1.38 to
      6.50) increase in risk when adjusted for the other factors. Intake of milk and
      vegetables both showed inverse linear relationships to being a case. CONCLUSIONS:
      This study suggests that dietary factors during childhood are an important
      influence in determining the expression of wheezy illness, after allowing for
      urban/rural residence, sex, family history, and atopy. The findings are
      consistent with previous studies in adults and with the hypothesis that change in
      diet has been a determinant of the worldwide increases in asthma and allergies.

PMID- 10950898
TI  - Salmeterol in paediatric asthma.
AB  - BACKGROUND: The addition of long acting inhaled beta(2) agonists is recommended
      at step 3 of the British guidelines on asthma management but a recent study
      suggested no additional benefit in children with asthma. METHODS: The aim of this
      study was to compare, in a double blind, three way, crossover study, the effects
      of the addition of salmeterol 50 microg bd, salmeterol 100 microg bd, and
      salbutamol 200 microg qds in asthmatic children who were symptomatic despite
      treatment with inhaled corticosteroids in a dose of at least 400 microg/day over
      a one month period. Symptom scores, morning and evening peak expiratory flow
      (PEF) rates, use of rescue medication, spirometric indices, and histamine
      challenge were measured. RESULTS: Forty five children aged 5-14 years were
      enrolled. All three treatments improved asthma control, morning and evening PEF
      rates, and spirometric indices with no change in bronchial hyperreactivity. Mean
      morning PEF was significantly better during the salmeterol treatment periods than
      with salbutamol treatment (p<0.05). The analysis of mean morning PEF gave an
      estimated treatment difference of 9.6 l/min for salmeterol 50 microg bd versus
      salbutamol 200 microg qds (95% confidence interval (CI) 2.1 to 17.1), and an
      estimated treatment difference of 13.8 l/min for salmeterol 100 microg bd versus
      salbutamol 200 microg qds (95% CI 6.0 to 21.5). There were no significant
      differences between the two doses of salmeterol and all treatments were well
      tolerated. CONCLUSIONS: In this population of moderate to severe asthmatic
      children on inhaled corticosteroids, salmeterol in a dose of either 50 microg bd
      or 100 microg bd is significantly more effective at increasing the morning PEF
      rate over a one month period than salbutamol 200 microg qds. The data provided no
      significant evidence of a difference in efficacy between the two doses of
      salmeterol, 50 microg and 100 microg. A trial of salmeterol 100 microg bd may be
      worth considering in those still symptomatic on the lower dose.

PMID- 10950899
TI  - Which spirometric indices best predict subsequent death from chronic obstructive
      pulmonary disease?
AB  - BACKGROUND: Previous epidemiological studies have related mortality from chronic
      obstructive pulmonary disease (COPD) to forced expiratory volumes (FEV(1) or
      FEV(0.75)) and it is unknown whether other spirometric indices might have greater
      predictive power. METHODS: A case-control study of fatal COPD was conducted
      within a cohort of London civil servants who performed forced expiratory
      spirograms in 1967-9 and were followed up for mortality over 20 years. The
      spirograms of 143 men who died of COPD (ICD8 491, 492 or 519.8) were compared
      with those of 143 controls individually matched for age, height, and smoking
      habit who survived longer than their matched case. Flow rates in different parts
      of the spirogram were compared within case-control pairs and analysed as
      predictors of fatal COPD by conditional logistic regression. RESULTS: Within pair
      case:control ratios of FEV(1), mid expiratory flow rates (e.g. FEF(50-75)) and
      FEF(75-85) were highly intercorrelated (r>0.7) but correlations with FEF(85-95)
      were weaker (r<0.5). All indices except the FEV(1)/FVC ratio were stronger
      predictors of death from COPD within the first 10 years than of later deaths (15
      19 years). After adjustment for FEV(1), mid expiratory flow rates independently
      predicted fatal COPD but end expiratory flow rates did not. The FEV(1) adjusted
      mortality ratios associated with a 10% decrement in each index were 2.24 (95% CI
      1.54 to 3.76) for FEF(50-75), 1.20 (95% CI 1.00 to 1.42) for FEF(75-85), and 1.10
      (95% CI 0.96 to 1.26) for FEF(85-95). CONCLUSION: This study confirms FEV(1) and
      mid expiratory flow rates as powerful predictors of mortality from COPD, and
      suggests that measurement of end expiratory flow rates would add little extra
      predictive information.

PMID- 10950900
TI  - Recent trends in physician diagnosed COPD in women and men in the UK.
AB  - BACKGROUND: Recent trends in physician diagnosed chronic obstructive pulmonary
      disease (COPD) in the UK were estimated, with a particular focus on women.
      METHODS: A retrospective cohort of British patients with COPD was constructed
      from the General Practice Research Database (GPRD), a large automated database of
      UK general practice data. Prevalence and all-cause mortality rates by sex,
      calendar year, and severity of COPD, based on treatment only, were estimated from
      January 1990 to December 1997. RESULTS: A total of 50 714 incident COPD patients
      were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual
      prevalence rates of physician diagnosed COPD in women rose continuously from
      0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01),
      rising to the rate observed in men in 1990. Increases in the prevalence of COPD
      were observed in women of all ages; in contrast, a plateau was observed in the
      prevalence of COPD in men from the mid 1990s. All-cause mortality rates were
      higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a
      consistently increased relative risk in men of 1.3 even after controlling for the
      severity of COPD. Significantly increased mortality rates were also observed in
      adults aged less than 65 years. The mean age at death was 76.5 years; patients
      with severe COPD died an average of three years before those with mild disease
      (p<0.01) and four years before the age and sex matched reference population.
      CONCLUSIONS: While prevalence rates of COPD in the UK seem to have peaked in men,
      they are continuing to rise in women. This trend, together with the ageing of the
      population and the long term cumulative effect of pack-years of smoking in women,
      is likely to increase the present burden of COPD in the UK.

PMID- 10950901
TI  - Increased sputum amino acid concentrations and auxotrophy of Pseudomonas
      aeruginosa in severe cystic fibrosis lung disease.
AB  - BACKGROUND: Pseudomonas aeruginosa may undergo a phenotypic change from the wild
      (prototrophic) type to an auxotrophic phenotype in the course of respiratory
      infection in patients with cystic fibrosis. The clinical significance of this is
      unclear. A study was undertaken to investigate whether the presence of auxotrophs
      of P aeruginosa in the sputum of patients with cystic fibrosis correlated with
      severity of respiratory disease, and whether increased sputum concentrations of
      amino acids were associated with the emergence of these forms. METHODS: Sixty
      adult patients with cystic fibrosis, colonised by P aeruginosa, were recruited
      and baseline clinical data including lung function were recorded. Serial sputum
      samples were obtained before, during, and after infective exacerbations where
      possible. These samples were used for routine microbiological culture, assessment
      of auxotrophy of P aeruginosa, measurement of amino acid content, and neutrophil
      elastase assay. RESULTS: Auxotrophy was common in patients with cystic fibrosis
      and 20 (33%) had a mean percentage auxotroph count of more than 50% total cfu/ml.
      The mean percentage auxotroph count was inversely correlated with forced
      expiratory volume in one second (FEV(1); tau = -0.194, p = 0.031). The median
      sputum amino acid concentration of the group was 12.5 mmol/l (range 0.13-40.6).
      The mean amino acid concentration in 33 subjects during infective exacerbations
      was 18.2 mmol/l (95% CI 15.1 to 21.3) compared with 12.3 mmol/l (95% CI 9.8 to
      14.8) when well (p = 0.001). The amino acid content of sputum was inversely
      correlated with FEV(1) (tau = -0.253, p = 0.005). CONCLUSIONS: P aeruginosa
      frequently exhibits auxotrophy in patients with cystic fibrosis, particularly in
      those with severe underlying pulmonary disease. The sputum amino acid content of
      patients with cystic fibrosis is high during infective exacerbations and
      correlates with pulmonary disease severity.

PMID- 10950902
TI  - Osteoporosis and osteopenia in adults and adolescents with cystic fibrosis:
      prevalence and associated factors.
AB  - BACKGROUND: Patients with cystic fibrosis (CF) have many risk factors for reduced
      bone mineral density (BMD). The aim of this study was to determine the prevalence
      of osteoporosis and osteopenia in a large cross section of patients and to
      identify risk factors. METHODS: All patients attending the regional centre were
      invited to participate in the study. Bone mineral density was measured at the
      lumbar spine, femoral neck, and for total body with a Lunar DPX-L densitometer.
      Multiple indices of disease severity were investigated, and liver and thyroid
      function, blood calcium, phosphate, 25-OH vitamin D, follicle stimulating and
      luteinising hormone, oestradiol, and testosterone levels were measured. Patients
      completed a four day prospective dietary diary. Exercise was assessed by a seven
      day activity recall questionnaire. Sexual development and treatment histories
      were obtained. The relationship between all these variables and BMD measurements
      was analysed. RESULTS: Sixty six percent of 114 patients assessed had osteopenia
      or osteoporosis. The Shwachman-Kulczycki (SK) clinical score (higher score = less
      severe disease) correlated significantly with BMD at the lumbar spine and femoral
      neck, and with total body BMD (p<0.001). There was a predicted increase of 0.0032
      g/cm(2) in lumbar spine BMD for every unit increase in the SK score. Oral steroid
      use was significantly associated with reduced BMD at the lumbar spine (p = 0.017)
      and femoral neck (p = 0.027). CONCLUSIONS: Osteopenia and osteoporosis are common
      findings in a heterogeneous population of adults with CF. Patients at most risk
      are those with severe disease and those who have used corticosteroids.

PMID- 10950904
TI  - Hunter's diseases of occupations

PMID- 10950905
TI  - Cystic fibrosis medical care

PMID- 10950903
TI  - Churg-Strauss syndrome associated with montelukast therapy.
AB  - Churg-Strauss syndrome is a rare form of eosinophilic vasculitis associated with
      asthma. There have been several recent case reports of the condition in
      association with leukotriene antagonists and it has been speculated that the
      Churg-Strauss syndrome was unmasked when oral corticosteroids were withdrawn. We
      report a case of Churg-Strauss syndrome associated with montelukast therapy in an
      asthmatic patient in whom there had been no recent oral corticosteroid use. We
      believe that this is the first such reported case and would suggest that
      clinicians need to be vigilant in all patients who develop systemic symptoms when
      starting treatment with leukotriene antagonists.

PMID- 10950911
TI  - An open-label trial of bromocriptine in nonfluent aphasia: a qualitative analysis
      of word storage and retrieval.
AB  - Anomia is a commonly found in aphasia and has been attributed to a loss of
      representations (storage deficit) or to a loss of access to these representations
      (retrieval deficit). Bromocriptine, a dopamine agonist, was tested on four
      patients, two men and two women, with nonfluent aphasia. The patients were tested
      in an open-label ABBA design using a stochastic model that measured the degree of
      storage and retrieval deficits. All patients showed significant improvements in
      word retrieval. Bromocriptine may be a useful adjunct in the treatment of
      selected patients with a nonfluent aphasia in which retrieval deficits play a
      major role.

PMID- 10950912
TI  - An fMRI study of sex differences in regional activation to a verbal and a spatial
      task.
AB  - Sex differences in cognitive performance have been documented, women performing
      better on some phonological tasks and men on spatial tasks. An earlier fMRI study
      suggested sex differences in distributed brain activation during phonological
      processing, with bilateral activation seen in women while men showed primarily
      left-lateralized activation. This blood oxygen level-dependent fMRI study
      examined sex differences (14 men, 13 women) in activation for a spatial task
      (judgment of line orientation) compared to a verbal-reasoning task (analogies)
      that does not typically show sex differences. Task difficulty was manipulated.
      Hypothesized ROI-based analysis documented the expected left-lateralized changes
      for the verbal task in the inferior parietal and planum temporal regions in both
      men and women, but only men showed right-lateralized increase for the spatial
      task in these regions. Image-based analysis revealed a distributed network of
      cortical regions activated by the tasks, which consisted of the lateral frontal,
      medial frontal, mid-temporal, occipitoparietal, and occipital regions. The
      activation was more left lateralized for the verbal and more right for the
      spatial tasks, but men also showed some left activation for the spatial task,
      which was not seen in women. Increased task difficulty produced more distributed
      activation for the verbal and more circumscribed activation for the spatial task.
      The results suggest that failure to activate the appropriate hemisphere in
      regions directly involved in task performance may explain certain sex differences
      in performance. They also extend, for a spatial task, the principle that
      bilateral activation in a distributed cognitive system underlies sex differences
      in performance.

PMID- 10950913
TI  - Interhemispheric inhibition, intrahemispheric activation, and lexical capacities
      of the right hemisphere: a tachistoscopic, divided visual-field study in normal
      subjects.
AB  - This study proposes that the lexical-semantic capacities of the right hemisphere
      (RH) are underestimated in normal subjects and reexamines them in a "dynamic
      model" framework. As expected, overloading the left hemisphere by combining a
      lexical-decision task presented in divided visual field with a concurrent heavy
      verbal memory load, and activating the RH by combining the lexical-decision task
      with a concurrent visuo-imaged memory load, lead to enhanced left visual field-RH
      lexical performance. The RH appears to support a larger lexical-semantic network
      than suggested in the literature, including representations for long and
      nonimageable words, and the accessibility threshold for the representations
      stored therein is modulated by hemispheric activation-inhibition mechanisms.

PMID- 10950914
TI  - How to avoid the fallacies of cognitive subtraction in brain imaging.
AB  - Functional neuroanatomy of cognitive processes is generally derived by
      subtraction of a control task from an experimental task. We show that this method
      is logically untenable and propose to replace it with an adaptation of the
      specific-effect method and of the additive-factor method. The basic flaw that
      undermines the subtractive method is the comparison between different tasks. We
      argue that the specific-effect method should be used when investigating
      activations produced by different levels of a qualitative variable, whereas the
      additive-factor method should be used for quantitative variables. The use of
      these methods allows one to distinguish between parallel and serial stages of
      processing and between local and distributed processing.

PMID- 10950915
TI  - Interictal discourse production in temporal lobe epilepsy.
AB  - Discourse production was investigated in 16 patients with left-temporal-lobe
      epilepsy (LTLE) and 17 neurologically normal relatives. Narrative was elicited
      with the Joanette and Goulet (1989) eight frame "Cowboy" cartoon on three
      immediately consecutive occasions. Variables of interest were fluency (words/s),
      speaking time, and word count. While controls produced increasingly concise forms
      of the story over repetitions, the TLE group became more verbose. Fluency did not
      not differentiate the groups. These findings suggest that LTLE is associated with
      macrolinguistic disturbances. The role of capacity limitations and motivational
      factors in TLE discourse production is discussed.

PMID- 10950916
TI  - Visual word form familiarity and attention in lateral difference during
      processing Japanese Kana words.
AB  - The purpose of this study was to examine the relationship between familiarity and
      laterality in reading Japanese Kana words. In two divided-visual-field
      experiments, three- or four-character Hiragana or Katakana words were presented
      in both familiar and unfamiliar scripts, to which subjects performed lexical
      decisions. Experiment 1, using three stimulus durations (40, 100, 160 ms),
      suggested that only in the unfamiliar script condition was increased stimulus
      presentation time differently affected in each visual field. To examine this
      lateral difference during the processing of unfamiliar scripts as related to
      attentional laterality, a concurrent auditory shadowing task was added in
      Experiment 2. The results suggested that processing words in an unfamiliar script
      requires attention, which could be left-hemisphere lateralized, while
      orthographically familiar kana words can be processed automatically on the basis
      of their word-level orthographic representations or visual word form.

PMID- 10950917
TI  - Language representation in the human brain: evidence from cortical mapping.
AB  - The manner in which the human brain processes grammatical-syntactic and lexical
      semantic functions has been extensively debated in neurolinguistics. The
      discreteness and selectivity of the representation of syntactic-morphological
      properties in the dominant frontal cortex and the representation of the lexical
      semantics in the temporo-parietal cortex have been questioned. Three right-handed
      adult male neurosurgical patients undergoing left craniotomy for intractable
      seizures were evaluated using various grammatical and semantic tasks during
      cortical mapping. The sampling of language tasks consisted of trials with
      stimulation (experimental) and without stimulation (control) from sites in the
      dominant fronto-temporo-parietal cortex The sampling of language implicated a
      larger cortical area devoted to language (syntactic-morphological and lexical
      semantic) tasks. Further, a large part of the fronto-parieto-temporal cortex was
      involved with syntactic-morphological functions. However, only the parieto
      temporal sites were implicated with the ordering of lexicon in sentence
      construction. These observations suggest that the representation of language in
      the human brain may be columnar or multilayered.

PMID- 10950918
TI  - Structural prominence hypothesis and Chinese aphasic sentence comprehension.
AB  - The Structural Prominence Hypothesis (SPH) proposed in Friederici and Gorrell
      (1998) has been claimed to find support from cross-linguistic data and to be
      empirically superior to linear strategies. In this article we evaluate the SPH
      against data of thematic-role-reversal comprehension of Chinese aphasics using
      Mandarin Chinese and Cantonese. We focus on the comprehension of Chinese
      relativized constructions for the reason that linear position and structural
      prominence diverge in these structures. The two types of strategies thus make
      different predictions about thematic reversal comprehension with respect to these
      structures. An examination of the performance patterns of Chinese aphasics from
      three different studies (Su & Law, 1993; Law & Leung, 1998a, 1998b) reveals a
      tendency on the part of the patients to make use of heuristics that takes into
      consideration the linear order of lexical NPs, not their structural prominence.
      Furthermore, their strategy does not necessarily make reference to verb position.

PMID- 10950919
TI  - The contribution of apraxic speech to working memory deficits in Parkinson's
      disease.
AB  - This article links two formerly separate areas of research associated with
      Parkinson's disease (PD): speech and memory. It is proposed that speech deficits
      occur in PD not merely at the level of muscular control, as is commonly termed
      dysarthria, but also at the level of speech planning and programming, more aptly
      described as a form of apraxia. It is further argued that PD patient groups
      exhibit small deficits in verbal span, and the link between apraxic speech and
      verbal span is elucidated via Baddeley's (1986) model of working memory. An
      experiment is described in which aspects of speech of 36 PD and 43 healthy
      control subjects were rated and classified, and measures of span and articulation
      rate for words of different syllable lengths were taken. Twenty-three PD subjects
      had dysarthric speech, while 14 of them had apraxic speech, which was associated
      with lower memory span scores for longer words. It is concluded that apraxic
      speech can be a source of reduced memory span in PD. In addition to implications
      for rehabilitation and therapeutic work with PD sufferers, these findings advance
      our theoretical understanding of the Parkinsonian syndrome.

PMID- 10950920
TI  - Auditory language comprehension: an event-related fMRI study on the processing of
      syntactic and lexical information.
AB  - The functional specificity of different brain areas recruited in auditory
      language processing was investigated by means of event-related functional
      magnetic resonance imaging (fMRI) while subjects listened to speech input varying
      in the presence or absence of semantic and syntactic information. There were two
      sentence conditions containing syntactic structure, i.e., normal speech
      (consisting of function and content words), syntactic speech (consisting of
      function words and pseudowords), and two word-list conditions, i.e., real words
      and pseudowords. The processing of auditory language, in general, correlates with
      significant activation in the primary auditory cortices and in adjacent
      compartments of the superior temporal gyrus bilaterally. Processing of normal
      speech appeared to have a special status, as no frontal activation was observed
      in this case but was seen in the three other conditions. This difference may
      point toward a certain automaticity of the linguistic processes used during
      normal speech comprehension. When considering the three other conditions, we
      found that these were correlated with activation in both left and right frontal
      cortices. An increase of activation in the planum polare bilaterally and in the
      deep portion of the left frontal operculum was found exclusively when syntactic
      processes were in focus. Thus, the present data may be taken to suggest an
      involvement of the left frontal and bilateral temporal cortex when processing
      syntactic information during comprehension.

PMID- 10950921
TI  - Characterization of the human TESTIN gene localized in the FRA7G region at
      7q31.2.
AB  - Cancer-associated chromosomal aberrations often involve regions containing
      fragile sites. FRA7G is a common aphidicolin-inducible fragile site at 7q31.2,
      showing loss of heterozygosity in human malignancies. To investigate the
      structure of FRA7G, we constructed a bacterial artificial chromosome contig
      spanning the region between marker D7S486 and Met H. Analysis of the FRA7G
      sequence allowed us to identify a gene encoding a 421-amino-acid protein with
      three LIM domains and 89% identity to murine Testin. We determined the genomic
      structure of the human TESTIN locus and characterized three alternative
      transcripts. Although TESTIN mRNA is expressed in all normal human tissues
      examined, we observed lack of expression in 22% of cancer cell lines and 44% of
      the cell lines derived from hematological malignancies. We further determined
      that in most of these cases the inactivation of TESTIN expression is due to
      methylation of a CpG island. Analysis of the TESTIN coding region in 26 tumor
      cell lines revealed three missense mutations. Our findings suggest that TESTIN
      may represent a candidate tumor suppressor gene at 7q31.2.

PMID- 10950922
TI  - Phemx, a novel mouse gene expressed in hematopoietic cells maps to the imprinted
      cluster on distal chromosome 7.
AB  - Phemx (Pan hematopoietic expression) is a novel murine gene expressed in
      developmentally regulated sites of hematopoiesis from early in embryogenesis
      through adulthood. Phemx is expressed in hematopoietic progenitors and mature
      cells of the three main hematopoietic lineages. Conceptual translation of the
      murine Phemx cDNA predicts a 25-kDa polypeptide with four hydrophobic regions and
      several potential phosphorylation sites, suggestive of a transmembrane protein
      involved in cell signaling. The PHEMX protein is structurally similar to
      tetraspanin CD81 (TAPA-1), a transmembrane protein involved in leukocyte
      activation, adhesion, and proliferation. Phemx maps to the distal region of
      chromosome 7, a segment of the mouse genome that contains a cluster of genes that
      exhibit genomic imprinting. However, imprinting analysis of Phemx at the whole
      organ level shows that it is biallelically expressed, suggesting that mechanisms
      leading to monoallelic expression are not imposed at this locus. The human PHEMX
      ortholog is specifically expressed in hematopoietic organs and tissues and, in
      contrast to murine Phemx, undergoes alternative splicing. The unique mode and
      range of Phemx expression suggest that it plays a role in hematopoietic cell
      function.

PMID- 10950923
TI  - Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus
      using 34 novel microsatellite markers, genomic structure, and exclusion of six
      known genes in the region.
AB  - An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously
      localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). This
      locus was discovered in a large, consanguineous Palestinian family. We have
      identified and ordered a total of 50 polymorphic microsatellite markers in
      21q22.3, comprising 16 published and 34 new markers, precisely mapped and ordered
      on BAC/cosmid contigs. Using these microsatellite markers, the locus for DFNB10
      has been refined to an area of less than 1 Mb between markers 1016E7.CA60 and
      1151C12.GT45. Six previously published cDNAs were mapped to this critical region,
      and their genomic structures were determined to facilitate mutation analysis in
      DFNB10. All six genes in this region (in order from centromere to telomere:
      White/ABCG1, TFF3, TFF2, TFF1, PDE9A, and NDUVF3) have been screened and
      eliminated as candidates for DFNB10. The new microsatellite markers and single
      nucleotide polymorphisms identified in this study should enable the refined
      mapping of other genetic diseases that map to 21q22.3. In addition, the critical
      region for DFNB10 has been reduced to a size amenable to an intensive positional
      cloning effort.

PMID- 10950924
TI  - C21orf5, a novel human chromosome 21 gene, has a Caenorhabditis elegans ortholog
      (pad-1) required for embryonic patterning.
AB  - To contribute to the development of the transcription map of human chromosome 21
      (HC21), we isolated a new transcript, C21orf5 (chromosome 21 open reading frame
      5), encoding a predicted 2298-amino-acid protein. Analysis of the genomic DNA
      sequence revealed that C21orf5 consists of 37 exons that extend over 130 kb and
      maps between the CBR3 (carbonyl reductase 3) and the KIAA0136 genes. Northern
      blot analyses showed a ubiquitously expressed RNA species of 8.5 kb. RNA in situ
      hybridization on brain sections of normal human embryos revealed a strong
      labeling in restricted areas of the cerebral cortex. In silico analysis of the
      deduced C21orf5 protein revealed several highly probable transmembrane segments
      but no known protein domains or homology with known proteins. However, there were
      significant homologies to several hypothetical Caenorhabditis elegans proteins
      and Drosophila melanogaster genomic sequences. To investigate the function of
      C21orf5, we isolated the cDNA of the C. elegans ortholog and performed double
      stranded RNA-mediated genetic interference experiments. The major phenotype
      observed in the progeny of injected animals was embryonic lethality. Most of the
      tissues of the embryo failed to undergo proper patterning during gastrulation,
      and morphogenesis did not occur; thus we termed the ortholog pad-1, for
      patterning defective 1. These results indicated that pad-1 is essential for the
      development and the survival of C. elegans. This study provides the first example
      of the use of C. elegans as a model to study the function of genes on human
      chromosome 21 that might be involved in Down syndrome.

PMID- 10950925
TI  - The FXYD gene family of small ion transport regulators or channels: cDNA
      sequence, protein signature sequence, and expression.
AB  - A gene family of small membrane proteins, represented by phospholemman and the
      gamma subunit of Na,K-ATPase, was defined and characterized by the analysis of
      more than 1000 related ESTs (expressed sequence tags). In addition to new and
      more complete cDNA sequence for known family members (including MAT-8, CHIF, and
      RIC), the findings included two new family members and new splicing variants. A
      large number of EST replicates made it possible to derive curated DNA sequence
      with higher confidence and accuracy than from the sequencing of individual
      clones. The family has a core motif of 35 invariant and conserved amino acids
      centered on a single transmembrane span. Features of each predicted protein
      product were compared, and tissue distributions were determined. The gene family
      was named FXYD (pronounced fix-id) in recognition of invariant amino acids in its
      signature motif. The abundant proteins are involved in the control of ion
      transport.

PMID- 10950926
TI  - Organization and conservation of the GART/SON/DONSON locus in mouse and human
      genomes.
AB  - The SON gene, which maps to human chromosome 21q22.1-q22.2, encodes a novel
      regulatory protein. Here we describe the organization of the Son locus in the
      mouse genome. The mouse Son gene spans a region of approximately 35 kb. The
      coding region is more than 8 kb in length and has been completely sequenced. The
      gene is organized into 11 coding exons and 1 noncoding 3'UTR exon, with over 70%
      of the coding region residing in one 5.7-kb exon. The gene contains at least one
      alternative exon, N/C exon 1, which can be used, by splicing, to generate a
      truncated form of the SON protein. Further investigation of the mouse Son locus
      has identified the genes directly flanking Son. The glycinamide ribonucleotide
      formyltransferase gene, Gart, is encoded 5' of Son in a head-to-head arrangement,
      with the start of both genes lying within 899 bp. Sequence comparison with the
      expressed sequence tagged database identified a novel gene within 65 bp of the 3'
      end of Son, which we have named Donson. In this unusually compact gene cluster,
      we have found overlap in the pattern of expression between Gart, Son, and Donson.
      However, at least two of these genes have very different functions. While GART is
      involved in purine biosynthesis, we find that SON shows the characteristics of
      "SR- type" proteins, which are involved in mRNA processing and gene expression.

PMID- 10950927
TI  - The human elongation factor 1 A-2 gene (EEF1A2): complete sequence and
      characterization of gene structure and promoter activity.
AB  - The eukaryotic elongation factor 1 A (eEF1A, formerly EF1alpha) is a key factor
      in protein synthesis, where it promotes the transfer of aminoacylated tRNAs to
      the A site of the ribosome. Two differentially expressed isoforms of eEF1A,
      designated eEF1A-1 and eEF1A-2, are found in mammals. Here we report the
      isolation and sequencing of the gene (HGMW-approved symbol EEF1A2) coding for the
      human eEF1A-2 isoform. Furthermore, we characterize the gene structure and the
      activity of the promoter. Isolation of overlapping clones from human libraries
      revealed that the human eEF1A-2 gene spans approximately 10 kb and consists of
      eight exons. The intron-exon boundaries of human EEF1A2 and EEF1A1 are conserved,
      yet the gene of the eEF1A-2 isoform is larger than the eEF1A-1 gene because of
      enlarged introns. Primer extension analysis identified the predominant
      transcription start site 166 bp upstream of the AUG codon. The start site maps to
      an adenine located within a consensus initiator element. Sequencing of a 2-kb 5'
      flanking promoter region revealed no TATA element. However, several putative cis
      regulatory elements were discovered. The 5'-promoter activity was characterized
      by transient transfection experiments. Progressive deletions of the upstream
      promoter region defined a minimal promoter region, ranging from -16 to +92, that
      is sufficient to drive transcription.

PMID- 10950928
TI  - Isolation and characterization of a human chromosome 21q22.3 gene (WDR4) and its
      mouse homologue that code for a WD-repeat protein.
AB  - To identify candidate genes for Down syndrome phenotypes or disorders that map to
      human chromosome 21q22.3, trapped exons are being used to isolate full-length
      transcripts. We isolated a full-length cDNA (WDR4) encoding a novel WD-repeat
      protein and its mouse homologue. Two RNA species of 1.5 and 2.1 kb were observed
      in human, with the 1.5-kb transcript being produced by a splicing event after the
      stop codon, and thus both transcripts encode the same putative 412-amino-acid
      protein containing four guanine nucleotide-binding WD repeats. The more highly
      expressed 1.5-kb transcript was expressed mainly in fetal tissues while the 2.1
      kb transcript showed a faint expression in most tissues. Two additional
      alternative splicing events of 270 and 52 nt within the coding region were
      observed. The WDR4 gene spans 37 kb and is divided into 11 coding exons. WDR4
      maps between PDE9A and NDUFV3, a region where several genetic disorders,
      including a form of manic-depressive psychosis, also map, and seven sequence
      variants observed in the WDR4 gene could be used in association studies.

PMID- 10950929
TI  - Canine heparan sulfate sulfamidase and the molecular pathology underlying
      Sanfilippo syndrome type A in Dachshunds.
AB  - Heparan sulfate sulfamidase (HSS) is a lysosomal exohydrolase that, when
      deficient, results in intralysosomal accumulation of heparan sulfate and the
      clinical phenotype of Sanfilippo syndrome type A. The first animal disease
      homolog of human Sanfilippo syndrome type A has been recently indentified in
      Dachshund littermates. To identify the molecular defect, the nucleotide sequences
      of the normal canine HSS gene and cDNA were determined using PCR-based
      approaches. The coding region showed 87% nucleotide homology, and 89% amino acid
      sequence homology, with human HSS. All exon-intron borders were conserved.
      Sequence analysis of the entire coding region with exon-intron boundaries was
      performed in the propositus, a healthy littermate, and six unrelated normal dogs.
      Comparison revealed a 3-bp deletion, 737-739delCCA, resulting in the loss of
      threonine at position 246 in both alleles of the propositus and in one allele of
      a healthy littermate. Prediction of the three-dimensional structure of canine
      HSS, based on homology with human arylsulfatases A and B, suggested the
      pathogenic effect of this deletion. Six other sequence variations in exons, and
      10 in introns, appear to be benign polymorphisms. This study supports the
      potential development of a canine model of Sanfilippo syndrome type A to evaluate
      gene therapy for this disorder.

PMID- 10950930
TI  - Isolation, tissue distribution, and chromosomal localization of the human
      activation-induced cytidine deaminase (AID) gene.
AB  - The gene encoding activation-induced cytidine deaminase (AID), a member of the
      cytidine deaminase family, was isolated from a murine B cell lymphoma line,
      CH12F3-2, induced by combined stimulation of TGF-beta, IL-4, and CD40L. We have
      isolated the human orthologue of mouse AID cDNA, which has an open reading frame
      of 198 residues containing a conserved cytidine deaminase motif. The amino acid
      sequence of human AID is 92% identical to that of mouse AID. RT-PCR analysis of
      15 human tissues showed that AID mRNA is expressed strongly in lymph nodes and
      tonsils. The complete human AID gene consisting of five exons was isolated and
      mapped to chromosome 12p13 by fluorescence in situ hybridization.

PMID- 10950931
TI  - Human and mouse homologues of the Drosophila melanogaster tweety (tty) gene: a
      novel gene family encoding predicted transmembrane proteins.
AB  - We have cloned cDNA for TTYH1, a human homologue of the Drosophila melanogaster
      tweety (tty) gene. The 450-residue predicted protein shows 27% amino acid
      sequence identity (51% similarity) to the Drosophila protein, which contains an
      additional C-terminal repetitive region. A second Drosophila homologue exhibits
      42% identity (65% similarity) to the tty protein. Mouse (Ttyh1), macaque, and
      Caenorhabditis elegans homologues were also identified, and the complete coding
      sequence for the mouse gene was determined. The mouse protein is 91% identical to
      the human protein. Hydrophobicity analysis of the tty-related proteins indicates
      that they represent a new family of membrane proteins with five potential
      membrane-spanning regions. The yeast FTR1 and FTH1 iron transporter proteins and
      the mammalian neurotensin receptors 1 and 2 have a similar hydrophobicity
      profile, although there is no detectable sequence homology to the tty-related
      proteins. This suggests that the tweety-related proteins could be involved in
      transport of iron or other divalent cations or alternatively that they may be
      membrane-bound receptors. TTYH1 was mapped to chromosome 19q13.4 by FISH and by
      radiation hybrid mapping using the Stanford G3 panel.

PMID- 10950932
TI  - SMAR1, a novel, alternatively spliced gene product, binds the Scaffold/Matrix
      associated region at the T cell receptor beta locus.
AB  - Rearrangement and expression of the T cell receptor beta gene are critical events
      for early T lymphocyte development. To characterize cis-regulatory elements and
      their associated trans-factors that mediate these events, we have previously
      identified a nuclear matrix/scaffold-associated region, referred to as MARbeta,
      400 bp upstream of the Ebeta enhancer. Electrophoretic mobility shift assay
      showed that two known MAR-binding proteins, SATB1 and Cux, bind MARbeta. In this
      article, we report the identification of a novel MAR-binding protein, named
      SMAR1, that also binds MARbeta. SMAR1 shares homology with SATB1 and Cux in the
      MAR-binding domain/Cut repeat and also with the tetramerization domain of a B
      cell-specific MAR-binding protein, Bright. The binding of GST-SMAR1 fusion
      protein to MARbeta is inhibited by the presence of an excess amount of MAR
      containing DNA from the immunoglobulin kappa locus. Smar1 transcripts are most
      abundant in the thymus and are alternatively spliced. The smar1 gene maps to the
      distal portion of mouse chromosome 8 at a distance of 111.8 cM.

PMID- 10950933
TI  - Development of a 1.4-Mb BAC/PAC contig and physical map within the critical
      region for complete X-linked congenital stationary night blindness in Xp11.4.
AB  - A physical map internal to the markers DXS1368 and DXS228 was developed for the
      p11.4 region of the human X chromosome. Twenty-four BACs and 10 PACs with an
      average insert size of 149 kb were aligned to form a contig across an estimated
      1.4 Mb of DNA. This contig, which has on average fourfold clone coverage, was
      assembled by STS and EST content analysis using 46 markers, including 8 ESTs, two
      retinally expressed genes, and 22 new STSs developed from BAC- and PAC-derived
      DNA sequence. The average intermarker distance was 30 kb. This physical map
      provides resources for high-resolution mapping as well as suitable clones for
      large-scale sequencing efforts in Xp11.4, a region known to contain the gene for
      complete X-linked congenital stationary night blindness.

PMID- 10950934
TI  - Chromosomal localization, gene structure, and expression pattern of DDAH1:
      comparison with DDAH2 and implications for evolutionary origins.
AB  - Endogenously produced asymmetrically methylated arginine residues are competitive
      inhibitors of all three isoforms of nitric oxide synthase (NOS). The enzyme
      dimethylarginine dimethylaminohydrolase (DDAH) specifically hydrolyzes these
      asymmetrically methylated arginine residues to citrulline and methylamines.
      Previously we have proposed that regulation of asymmetric methylarginine
      concentration by DDAH may provide a novel mechanism for the regulation of NOS
      activity in vivo. Recently we reported the cloning of human DDAH and identified a
      novel human DDAH isoform (DDAH I and DDAH II, respectively). Here we report that
      the DDAH1 gene maps to chromosome 1p22 and confirm that DDAH2 maps to the MHC III
      region of chromosome 6p21.3. Extensive analysis of the distribution of DDAH1 and
      DDAH2 mRNA in 50 human tissues indicates differential expression of DDAH isoforms
      in brain regions, in immune cells, and during development. DDAH2 expression
      predominates in highly vascularized tissues that express the endothelial NOS
      isoform and in immune tissues that can express iNOS. Whereas DDAH2 is expressed
      at relatively high levels in all fetal tissues examined, DDAH1 expression varies
      little between fetal and adult tissues. The chromosomal localization of the DDAHs
      is consistent with gene duplication, and consistent with this, comparison of the
      gene structures indicates that the intron/exon organization is highly conserved.
      Phylogenetic analysis of DDAH sequences from diverse species suggests that DDAH
      gene duplication occurred prior to the emergence of bony fish some 400 million
      years ago. Overall the data suggest that DDAH2 may be the more ancient of the two
      genes.

PMID- 10950936
TI  - Functional characterization of the novel mutation IVS 8 (-11delC) (-14T>A) in the
      intron 8 of the glucocerebrosidase gene of two Italian siblings with Gaucher
      disease type I.
AB  - Gaucher disease, the most common glycolipid storage disease, can be caused by a
      large variety of mutations. We report here the identification and
      characterization of a novel mutation in the human glucocerebrosidase gene, IVS 8
      (-11delC) (-14T>A), in two siblings with Gaucher disease type I which occurs
      within the 3' end of intron 8. Both siblings were compound heterozygotes for the
      IVS 8 (-11delC) (-14T>A) mutation and for the c.626 G>C (R170P) substitution
      within exon 6. No mRNA species carrying the IVS 8 (-11delC) (-14T>A) mutation
      were detected by RT-PCR analysis of the RNA extracted from the patients'
      fibroblasts. To study the possible effects of the IVS 8 (-11delC) (-14T>A)
      sequence alteration on the splicing of the proximal exon 9, we have established
      an in vitro system generating a minigene carrying the genomic region of human
      glucocerebrosidase spanning from exon 8 to exon 10. Transfections into the human
      Hep3B cell line of the wild-type construct resulted in the expression of mRNA
      with the glucocerebrosidase exons correctly spliced. On the contrary,
      transfections of the construct carrying the IVS 8 (-11delC) (-14T>A) mutation
      resulted in the expression of mRNA with an 11-bp insertion located between the
      end of exon 8 and the beginning of exon 9. These results indicated that the
      5243T>A substitution created a new 3' splice site 11 bp upstream of the wild-type
      one, leading to the incorporation into the mRNA of these extra 11 bases.
      Moreover, the new 3' splice site created by this 5243T>A transversion was
      preferred over the wild-type one in 100% of cases. The in vitro studies suggest
      that, in the patients, the 11-bp inclusion causes a shift in the reading frame
      with the generation of a stop codon after codon 388 which undergoes early
      degradation.

PMID- 10950935
TI  - Single-step conversion of P1 and P1 artificial chromosome clones into yeast
      artificial chromosomes.
AB  - Large insert genomic clones are useful for generating transgenic animals,
      particularly when specific mutations are introduced. To facilitate manipulation
      of large genomic sequences, we developed a method of converting Escherichia coli
      P1 artificial chromosomes (PACs) into yeast artificial chromosomes (YACs). A
      shuttle vector, pMAX-121, was generated that contains elements needed to generate
      a YAC (cen4, ars, ura3, his, and two telomere segments) along with approximately
      1.3 kb of sequence homologous to P1 and PAC vector sequences. Cotransformation of
      yeast with the target PAC or P1 clone and pMAX-121 results in two homologous
      recombination events. The first, between the target clone and pMAX-121, results
      in a circular molecule. The second is an intramolecular recombination event
      between the two pMAX-121 telomere sequences, resulting in a linear molecule. The
      resulting YAC is stably maintained in yeast and can be further modified using
      homologous recombination. The method was used to convert a 201-kb PAC containing
      the human tau gene into a stable linear YAC. A second vector, pLys2-neo, was
      developed to retrofit the YAC with the yeast lys2 gene, a selectable marker
      replacing the yeast ura3 gene, and a Pgk-neo cassette that confers G418
      resistance to mammalian cells. The resulting YAC can be used for generating
      transgenic animals and stably transfected cell lines. Also, the lys2 marker
      facilitates introduction of mutations by homologous recombination.

PMID- 10950938
TI  - The expression pattern of the AML1 gene in non-Hodgkin's B-cell lymphomas and
      normal B lymphocytes.
AB  - We have studied the expression of the three human acute myeloid leukemia (AML)
      genes in primary samples of non-Hodgkin's B-cell lymphomas in which
      translocations involving these loci were not present. We found a widespread
      expression of the three AML genes in all the lymphoma samples as well as in the
      purified normal B-lymphocytes. Thus, the presence of the three mRNAs "per se"
      does not allow the identification of the pathological status. However, AML1
      showed a different transcription pattern in the neoplastic tissues with respect
      to the normal B-cells. The AML1b isoform proved to be peculiar to this lymphoma.
      Our data support the idea that qualitative and quantitative alterations of AML1
      gene expression deriving from deregulating mechanisms other than translocations
      may be involved in this malignancy. The usage of two differently regulated
      promoters driving the expression of the transcripts AML1b and AML1c may be one of
      these mechanisms. Finally, we report the presence of a new alternatively spliced
      transcript in normal B-cells.

PMID- 10950937
TI  - Gamma heavy chain disease in man: independent structural abnormalities and
      reduced transcription of a functionally rearranged lambda L-chain gene result in
      the absence of L-chains.
AB  - Human Ig heavy chain diseases of the alpha and gamma classes are characterized by
      the absence of light chain production as well as the disease-defining
      abnormalities in the heavy chain protein. Prior studies have suggested
      concomitant structural defects in productively rearranged L-chain genes as the
      reason for the absent L-chain proteins. We have found that the single rearranged
      lambda L-chain gene in the OMM heavy chain disease (HCD) cell line has a mutation
      in the splice donor site at the 3' end of the J exon, resulting in direct
      splicing of the 3' end of the leader to the acceptor site of the constant region.
      The cells contain an mRNA consisting of the leader-coding region joined directly
      to the constant region. The V-region exon is skipped and the shortened mRNA is
      translated into a truncated protein containing no V-region amino acids. We have
      also noted that, in contrast to most normal and neoplastic Ig-producing cells,
      the OMM cells produce an excess of heavy to light chain mRNA as well as protein.
      The excess is independent of the structural gene abnormality and is due to a low
      level of L-chain transcription, which can be increased by fusing the HCD cell to
      the murine myeloma cell line NS-1 or transfecting the defective OMM L-chain gene
      into a murine plasma cell. The latter data suggest that the OMM cells either lack
      a transcription factor present in mature plasma cells or have a functional
      repressor of L-chain transcription.

PMID- 10950939
TI  - Detailed mapping of methylcytosine positions at the CpG island surrounding the Pa
      promoter at the bcr-abl locus in CML patients and in two cell lines, K562 and
      BV173.
AB  - Chronic myelogenous leukemia (CML) is associated with a translocation of the
      protooncogene c-abl from chromosome 9 to chromosome 22, where it fuses to
      proximal exons of the bcr gene. The expression of the hybrid gene bcr-abl is
      regulated by the bcr promoter and results in a translation product with high
      tyrosine kinase activity. In most CML cases, one of two abl promoters (Pa) is
      nested within the bcr-abl transcription unit, but appears to be usually silent.
      Recently, de novo methylation of the Pa region and its correlation with disease
      progression were reported. As these previous studies were limited to the use of
      methylation-sensitive restriction endonucleases, our aim here was to obtain a
      complete map of methylcytosines and its variants in CML patients and in model
      cell lines. To achieve this, bisulfite conversion of cytosines (but not
      methylcytosines) to uracils in genomic DNA was employed. After modification, the
      region of interest was PCR-amplified and the products were cloned and sequenced.
      The results show methylation at a high level and in a homogenous pattern in the
      BV173 cell line, corresponding to the translocated abl alleles. Variant
      methylation observed in K562 cells correlates with multiple bcr-abl loci and an
      intact chromosome 9. Patients that were methylation-positive in restriction
      analysis showed sporadic and heterogenous occurrence of methylcytosines in
      bisulfite modification assays. Corresponding results were obtained using a
      quantitative Southern analysis of the extent of methylation. We conclude that
      restriction analysis combined with PCR is able to find rare cases of
      hypermethylation, e. g., for diagnostic purposes, but does not reflect the
      dominating level of methylation in Ph-positive cells.

PMID- 10950940
TI  - Exclusion of ZIRTL as candidate gene of juvenile hemochromatosis and refinement
      of the critical interval on 1q21.
AB  - Hemochromatosis type 2 (HFE2) or juvenile hemochromatosis (JH) is a rare
      recessive disorder that causes iron overload, characterized by early onset and
      severe clinical course. The JH locus maps to chromosome 1q, in a 4-cM region
      encompassing markers D1S442 and D1S2347. Recently a gene named ZIRTL has been
      characterized and mapped to 1q21. This gene belongs to a family of divalent metal
      ion-transporting genes that encode for proteins involved in transport of
      different metals, including iron. Thus, the ZIRTL gene represents a positional
      and functional candidate for JH. Here we further restrict the candidate region
      through segregation analysis of two new polymorphic markers and haplotype
      analysis in JH families. Furthermore, we exclude ZIRTL as a JH candidate gene
      showing that it maps outside the critical interval and that its genomic sequence
      is normal in three patients.

PMID- 10950941
TI  - Selective inhibition of NF-kB activation and TNF-alpha production in macrophages
      by red blood cell-mediated delivery of dexamethasone.
AB  - Glucocorticoids are a widely used class of anti-inflammatory and
      immunosuppressive drugs, but their therapeutic use is limited by endocrine and
      metabolic side effects that they produce when given systemically. Since cells of
      the monocyte/macrophage lineage play an important role in the pathogenesis of
      several autoimmune and inflammatory diseases, a drug-delivery system which
      targets phagocytic cells was studied. We had previously demonstrated that
      dexamethasone, a potent glucocorticoid analogue, can be encapsulated in
      erythrocytes and selectively delivered to macrophages. In addition,
      lipopolysaccharide (LPS) stimulation of dexamethasone-targeted macrophages
      results in the suppression of TNF-alpha secretion. In this paper we demonstrate
      that the administration of dexamethasone to macrophages by means of opsonized red
      blood cells allows efficient interference with NF-kB activation. This NF-kB
      repression was in part mediated by induction of IkBalpha gene transcription and,
      as a consequence, by an increased rate of IkBalpha protein synthesis.
      Furthermore, NF-kB inactivation correlated with downmodulation of TNF-alpha mRNA
      expression, demonstrating that suppression of TNF-alpha production in
      dexamethasone-targeted cells occurs at the transcriptional level.

PMID- 10950942
TI  - A beta-2-adrenergic receptor activates adenylate cyclase in human erythrocyte
      membranes at physiological calcium plasma concentrations.
AB  - More information is needed about the subtype of the beta-adrenergic receptor
      coupled to the G-protein-adenylate cyclase (AC) system in human erythrocytes and
      about the optimal experimental conditions to study this system. In this study we
      describe the characteristics of spontaneous and beta-agonist-activated AC in
      human erythrocytes. Human erythrocyte membranes were isolated and AC activity was
      utilized to assess the quantity of cAMP. Our data show that the subtype beta-2 is
      the functional beta-adrenergic receptor involved in such activation; this
      modifies the beta-adrenergic-stimulated activity of AC in human erythrocytes.
      Isoproterenol in a medium with calcium (1-10 mM, range that includes
      physiological plasma concentrations) enhances the activation of AC; this effect
      was blocked by propranolol, but not by atenolol. We conclude that in human
      erythrocytes subtype beta-2 is the functional beta-adrenergic receptor and that
      such a response depends to a large extent on Ca(2+) concentrations.

PMID- 10950943
TI  - A common intron 3 mutation (IVS3 -48c-->g) leads to misdiagnosis of the c.845G-
      >A (C282Y) HFE gene mutation.
AB  - Amplification of the region of the HFE gene that contains the c.845G-->A (C282Y)
      mutation is usually performed using one amplimer that binds to a sequence in
      intron 3 and another that binds to a sequence in intron 4. Previously, a mutation
      that interferes with efficient binding to the intron 4 site has been described.
      We now find that another common mutation in intron 3, IVS3 -48c-->g, prevents
      binding of the amplimer to that site. This polymorphism occurs at a gene
      frequency of 0.128 in the African-American population and at a frequency of only
      0.006 in the European population. DNA samples heterozygous for the IVS3 -48c-->g
      polymorphism and C282Y were undistinguishable from samples homozygous for the
      C282Y mutation when they were examined by allele-specific oligonucleotide
      hybridization (ASOH) and showed only a weak normal band when examined by
      electrophoresis following restriction endonuclease digestion. Although the
      polymorphism occurs in a DNA sequence almost identical to the intron 3 splice
      donor site, we found no evidence of alternative splice forms. Moreover, serum
      iron, transferrin saturation, and serum ferritin levels were normal in subjects
      heterozygous for the polymorphism. It appears, therefore, that the main
      importance of this polymorphism is that it may lead to misdiagnosis of
      heterozygotes for the C282Y mutation as homozygotes. We therefore recommend
      exonic amplimers that avoid sites that contain polymorphisms and that can be
      multiplexed for detection of the c.187C-->G (H63D) and c.845G-->A (C282Y)
      mutations.

PMID- 10950944
TI  - Human bone marrow stromal cell: coexpression of markers specific for multiple
      mesenchymal cell lineages.
AB  - The role of hematopoietic stem cells in blood cell development is reasonably
      understood, whereas the identity and the function of bone marrow stromal cells
      are much less clear. Using stromal cells in bone marrow cultures of the Dexter
      type, a favorite medium for the study of hematopoiesis, we show that stromal
      cells actually represent a unique cell type. Conventional wisdom has held that
      stromal cells in Dexter cultures comprise a mixture of macrophages, hematopoietic
      cells, adipocytes, osteoblasts, fibroblasts, muscle cells, and endothelial cells.
      Our findings demonstrate that Dexter cultures consist of three cell types:
      macrophages ( approximately 35%), hematopoietic cells ( approximately 5%), and
      nonhematopoietic cells ( approximately 60%). We have purified the
      nonhematopoietic cells free of macrophages and hematopoietic cells to produce
      compelling evidence that they in fact represent a single cell type
      (multidifferentiated mesenchymal progenitor cell, MPC) which coexpresses genes
      specific for various mesenchymal cell lineages including adipocytes, osteoblasts,
      fibroblasts, and muscle cells. We further show that these multi- or
      pluridifferentiated MPCs are capable of supporting hematopoiesis by demonstrating
      the expression of several hematopoietic growth factors and extracellular matrix
      receptors including G-CSF, SCF, VCAM-1, ICAM-1, and ALCAM. Since the MPCs can be
      easily purified to near homogeneity (95%), they can be of value in enhancing
      engraftment of hematopoietic stem cells. Also, this new understanding of bone
      marrow stromal cells as "one cell with many different faces" promises to advance
      our knowledge of regulatory cellular interactions within bone marrow.

PMID- 10950945
TI  - Detection of small populations of CD59-deficient erythrocytes in patients with
      aplastic anemia or myelodysplastic syndrome and normal individuals.
AB  - To detect a small population of blood cells with a deficiency of glycosyl
      phosphatidylinositol (GPI)-anchored protein, we evaluated the expression of CD59
      by flow cytometry on one million erythrocytes, which is about 100 times more than
      the number of erythrocytes tested by our standard immunoassay. Blood samples from
      healthy volunteers, patients with aplastic anemia (AA), and patients with
      myelodysplastic syndrome (MDS), who all showed no detectable GPI deficiency by
      the standard assay, were investigated. The numbers of CD59-deficient erythrocytes
      were 5 to 145/10(6) erythrocytes in the healthy volunteers (mean 29.2), and one
      of the volunteers had an increase in the deficient cells exceeding the mean + 3
      SD (141.7), a normal limit. A CD59-deficient population was detected in 6 of the
      21 (28.6%) patients with AA and 5 of the 18 (27.8%) patients with MDS. The new
      assay was performed again in 5 of these 11 patients and the normal individual who
      had the CD59-deficient populations at 6 and 12 months after the initial study.
      The number of deficient cells gradually increased in 1 patient with MDS (from 511
      to 2892/10(6) erythrocytes), while the numbers of the other 4 patients showed a
      tendency to decline, although the deficient populations were repeatedly detected
      on most of the occasions. Changes in the number of the deficient cells were also
      seen in the healthy volunteer, but they were rather rapid; the numbers changed
      from 145 to 5661 and then to 18/10(6) erythrocytes within 3 months. The CD59
      assay used in this study is easy to perform and enabled us to detect less than 1%
      GPI-deficient cells.

PMID- 10950946
TI  - Dramatic decline in circulating intercellular adhesion molecule-1 concentration
      on quitting tobacco smoking.
AB  - The concentration of soluble ICAM-1 (sICAM-1) is significantly elevated in
      smokers, but it is unclear if smoking is the direct cause of elevated sICAM-1
      levels, if the relationship between smoking and sICAM-1 level is dose-dependent,
      and if smoking cessation may lead to a decline in sICAM-1. We sought to clarify
      the relationship between smoking and sICAM-1 in a group of smokers who quit
      smoking for 1 year (n = 30) and a control group who continued to smoke (n = 30).
      A dose-dependent relationship between plasma sICAM-1 concentration and daily
      cigarette consumption (P = 0.02), plasma cotinine level (P = 0.02), and expired
      CO level (P = 0.007) was observed at baseline (n = 60). The mean change in sICAM
      1 concentration after 52 weeks was greater for quitters than for continuing
      smokers (mean difference = -71.1 ng/ml, P < 0.001). The influence of smoking on
      sICAM-1 needs to be carefully considered in clinical trials. Soluble ICAM-1
      remains bioactive and may contribute to pathogenic processes; therefore,
      reduction in the concentration of circulating ICAM-1 molecules may directly
      contribute to the health benefits associated with smoking cessation.

PMID- 10950947
TI  - Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its
      role in the death receptor pathway.
AB  - Smac/DIABLO is a mitochondrial protein that is released along with cytochrome c
      during apoptosis and promotes cytochrome c-dependent caspase activation by
      neutralizing inhibitor of apoptosis proteins (IAPs). We provide evidence that
      Smac/DIABLO functions at the levels of both the Apaf-1-caspase-9 apoptosome and
      effector caspases. The N terminus of Smac/DIABLO is absolutely required for its
      ability to interact with the baculovirus IAP repeat (BIR3) of XIAP and to promote
      cytochrome c-dependent caspase activation. However, it is less critical for its
      ability to interact with BIR1/BIR2 of XIAP and to promote the activity of the
      effector caspases. Consistent with the ability of Smac/DIABLO to function at the
      level of the effector caspases, expression of a cytosolic Smac/DIABLO in Type II
      cells allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced
      apoptosis. Combined, these data suggest that Smac/DIABLO plays a critical role in
      neutralizing IAP inhibition of the effector caspases in the death receptor
      pathway of Type II cells.

PMID- 10950948
TI  - The Yersinia protein kinase A is a host factor inducible RhoA/Rac-binding
      virulence factor.
AB  - The pathogenic yersiniae inject proteins directly into eukaryotic cells that
      interfere with a number of cellular processes including phagocytosis and
      inflammatory-associated host responses. One of these injected proteins, the
      Yersinia protein kinase A (YpkA), has previously been shown to affect the
      morphology of cultured eukaryotic cells as well as to localize to the plasma
      membrane following its injection into HeLa cells. Here it is shown that these
      activities are mediated by separable domains of YpkA. The amino terminus, which
      contains the kinase domain, is sufficient to localize YpkA to the plasma membrane
      while the carboxyl terminus of YpkA is required for YpkAs morphological effects.
      YpkAs carboxyl-terminal region was found to affect the levels of actin-containing
      stress fibers as well as block the activation of the GTPase RhoA in Yersinia
      infected cells. We show that the carboxyl-terminal region of YpkA, which contains
      sequences that bear similarity to the RhoA-binding domains of several eukaryotic
      RhoA-binding kinases, directly interacts with RhoA as well as Rac (but not Cdc42)
      and displays a slight but measurable binding preference for the GDP-bound form of
      RhoA. Surprisingly, YpkA binding to RhoA(GDP) affected neither the intrinsic nor
      guanine nucleotide exchange factor-mediated GDP/GTP exchange reaction suggesting
      that YpkA controls activated RhoA levels by a mechanism other than by simply
      blocking guanine nucleotide exchange factor activity. We go on to show that YpkAs
      kinase activity is neither dependent on nor promoted by its interaction with RhoA
      and Rac but is, however, entirely dependent on heat-sensitive eukaryotic factors
      present in HeLa cell extracts and fetal calf serum. Collectively, our data show
      that YpkA possesses both similarities and differences with the eukaryotic
      RhoA/Rac-binding kinases and suggest that the yersiniae utilize the Rho GTPases
      for unique activities during their interaction with eukaryotic cells.

PMID- 10950949
TI  - Identification of residues important both for primary receptor binding and
      specificity in fibroblast growth factor-7.
AB  - Fibroblast growth factors (FGFs) mediate a multitude of physiological and
      pathological processes by activating a family of tyrosine kinase receptors
      (FGFRs). Each FGFR binds to a unique subset of FGFs and ligand binding
      specificity is essential in regulating FGF activity. FGF-7 recognizes one FGFR
      isoform known as the FGFR2 IIIb isoform or keratinocyte growth factor receptor
      (KGFR), whereas FGF-2 binds well to FGFR1, FGFR2, and FGFR4 but interacts poorly
      with KGFR. Previously, mutations in FGF-2 identified a set of residues that are
      important for high affinity receptor binding, known as the primary receptor
      binding site. FGF-7 contains this primary site as well as a region that restricts
      interaction with FGFR1. The sequences that confer on FGF-7 its specific binding
      to KGFR have not been identified. By utilizing domain swapping and site-directed
      mutagenesis we have found that the loop connecting the beta4-beta5 strands of FGF
      7 contributes to high affinity receptor binding and is critical for KGFR
      recognition. Replacement of this loop with the homologous loop from FGF-2
      dramatically reduced both the affinity of FGF-7 for KGFR and its biological
      potency but did not result in the ability to bind FGFR1. Point mutations in
      residues comprising this loop of FGF-7 reduced both binding affinity and
      biological potency. The reciprocal loop replacement mutant (FGF2-L4/7) retained
      FGF-2 like affinity for FGFR1 and for KGFR. Our results show that topologically
      similar regions in these two FGFs have different roles in regulating receptor
      binding specificity and suggest that specificity may require the concerted action
      of distinct regions of an FGF.

PMID- 10950950
TI  - Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican,
      to L-selectin, P-selectin, and CD44.
AB  - Here we show that a large chondroitin sulfate proteoglycan, versican, derived
      from a renal adenocarcinoma cell line ACHN, binds L-selectin, P-selectin, and
      CD44. The binding was mediated by the interaction of the chondroitin sulfate (CS)
      chain of versican with the carbohydrate-binding domain of L- and P-selectin and
      CD44. The binding of versican to L- and P-selectin was inhibited by CS B, CS E,
      and heparan sulfate (HS) but not by any other glycosaminoglycans tested. On the
      other hand, the binding to CD44 was inhibited by hyaluronic acid, chondroitin
      (CH), CS A, CS B, CS C, CS D, and CS E but not by HS or keratan sulfate. A cross
      blocking study indicated that L- and P-selectin recognize close or overlapping
      sites on versican, whereas CD44 recognizes separate sites. We also show that
      soluble L- and P-selectin directly bind to immobilized CS B, CS E, and HS and
      that soluble CD44 directly binds to immobilized hyaluronic acid, CH, and all the
      CS chains examined. Consistent with these results, structural analysis showed
      that versican is modified with at least CS B and CS C. Thus, proteoglycans
      sufficiently modified with the appropriate glycosaminoglycans should be able to
      bind L-selectin, P-selectin, and/or CD44.

PMID- 10950951
TI  - E-cadherin-mediated cell-cell attachment activates Cdc42.
AB  - E-cadherin is a transmembrane protein that mediates Ca(2+)-dependent cell-cell
      adhesion. Cdc42, a member of the Rho family of small GTPases, participates in
      cytoskeletal rearrangement and cell cycle progression. Recent evidence reveals
      that members of the Rho family modulate E-cadherin function. To further examine
      the role of Cdc42 in E-cadherin-mediated cell-cell adhesion, we developed an
      assay for active Cdc42 using the GTPase-binding domain of the Wiskott-Aldrich
      syndrome protein. Initiation of E-cadherin-mediated cell-cell attachment
      significantly increased in a time-dependent manner the amount of active Cdc42 in
      MCF-7 epithelial cell lysates. By contrast, Cdc42 activity was not increased
      under identical conditions in MCF-7 cells incubated with anti-E-cadherin
      antibodies nor in MDA-MB-231 (E-cadherin negative) epithelial cells. By fusing
      the Wiskott-Aldrich syndrome protein/GTPase-binding domain to a green fluorescent
      protein, activation of endogenous Cdc42 by E-cadherin was demonstrated in live
      cells. These data indicate that E-cadherin activates Cdc42, demonstrating bi
      directional interactions between the Rho- and E-cadherin signaling pathways.

PMID- 10950952
TI  - Perinuclear localization and insulin responsiveness of GLUT4 requires
      cytoskeletal integrity in 3T3-L1 adipocytes.
AB  - The GLUT4 glucose transporter resides mostly in perinuclear membranes in
      unstimulated 3T3-L1 adipocytes and is acutely translocated to the cell surface in
      response to insulin. Using a novel method to purify intracellular GLUT4-enriched
      membranes, we identified by mass spectrometry the intermediate filament protein
      vimentin and the microtubule protein alpha-tubulin as components of these
      membranes. Immunoelectron microscopy of the GLUT4-containing membranes also
      revealed their association with these cytoskeletal proteins. Disruption of
      intermediate filaments and microtubules in 3T3-L1 adipocytes by microinjection of
      a vimentin-derived peptide of the helix initiation 1A domain caused marked
      dispersion of perinuclear GLUT4 to peripheral regions of the cells. Inhibition of
      the microtubule-based motor dynein by brief cytoplasmic acidification of cultured
      adipocytes also dispersed perinuclear GLUT4 and inhibited insulin-stimulated
      GLUT4 translocation to the cell surface. Insulin sensitivity was restored as
      GLUT4 was again concentrated near the nucleus upon recovery of cells in
      physiological buffer. These data suggest that GLUT4 trafficking to perinuclear
      membranes of cultured adipocytes is directed by dynein and is required for
      optimal GLUT4 regulation by insulin.

PMID- 10950953
TI  - Expression of functional metabotropic glutamate receptors in primary cultured rat
      osteoblasts. Cross-talk with N-methyl-D-aspartate receptors.
AB  - Osteoblasts and osteoclasts express functional N-methyl-d-aspartate (NMDA)
      receptors, which participate in regulation of bone matrix. In rat femoral
      osteoblasts held in whole cell clamp there is a robust NMDA current but little if
      any response to l-glutamate. We have investigated expression of metabotropic
      glutamate receptors (mGluRs) in these cells. By reverse transcription polymerase
      chain reaction, we have detected expression of mGluR1b (but not mGluR1a, 2, 3, 4,
      5, or 6). Blockade of mGluRs with (+/-)-alpha-methyl-carboxyphenyl-glycine
      resulted in an enlarged l-glutamate-induced current that resembled the response
      to NMDA. Conversely, prior stimulation of mGluRs with trans-(+/-)-1-amino-1, 3
      cyclopentanedicarboxylic acid (1S,3R-ACPD; mGluR agonist) reduced the NMDA
      induced current by 77%. Monitoring of [Ca(2+)](i) showed that NMDA induced a
      sustained elevation of [Ca(2+)](i), which was dependent upon [Ca(2+)](o).
      Treatment with 1S,3R-ACPD generated an initial transient that was independent of
      [Ca(2+)](o), followed by a sustained, [Ca(2+)](o)-dependent phase, a response
      consistent with phospholipase C-mediated mobilization of stored Ca(2+).
      Investigations of the interaction between the two receptors confirmed inhibitory
      modulation of the NMDA receptor-induced rise in [Ca(2+)](i) by mGluRs.
      Parathyroid hormone, which also activates phospholipase C in osteoblasts, had a
      similar inhibitory effect on the NMDA receptor-induced [Ca(2+)](i) response.
      Elevation of [Ca(2+)](i) mediated by mGluR activation was reduced by subsequent
      stimulation of NMDA receptors. This is the first description of mGluRs in bone
      and shows that complex glutamatergic signaling can occur in this tissue.

PMID- 10950954
TI  - Calcium and cAMP signals differentially regulate cAMP-responsive element-binding
      protein function via a Rap1-extracellular signal-regulated kinase pathway.
AB  - Two major intracellular signals that regulate neuronal function are calcium and
      cAMP. In many cases, the actions of these two second messengers involve long term
      changes in gene expression. One well studied target of both calcium and cAMP
      signaling is the transcription factor cAMP-responsive element-binding protein
      (CREB). Multiple signaling pathways have been shown to contribute to the
      regulation of CREB-dependent transcription, including both protein kinase A (PKA)
      and mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase
      (ERK)-dependent kinase cascades. We have previously described a mechanism by
      which cAMP and calcium influx may stimulate ERKs in neuronal cells. This pathway
      involves the PKA-dependent activation of the Ras-related small G-protein, Rap1,
      and subsequent stimulation of the neuronal Raf isoform, B-Raf. In this study, we
      examined the contribution of the Rap1-ERK pathway to the control of gene
      transcription by calcium influx and cAMP. Using the PC12 cell model system, we
      found that both calcium influx and cAMP stimulated CREB-dependent transcription
      via a Rap1-ERK pathway, but this regulation occurred through distinct mechanisms.
      Calcium-mediated phosphorylation of CREB through the PKA-Rap1-ERK pathway. In
      contrast, cAMP phosphorylated CREB via PKA directly but required a Rap1-ERK
      pathway to activate a component downstream of CREB phosphorylation and CREB
      binding protein recruitment. These data suggest that the Rap1/B-Raf signaling
      pathway may have an important role in the regulation of CREB-dependent gene
      expression.

PMID- 10950955
TI  - Cyclic nucleotide regulation of Na+/glucose cotransporter (SGLT1) mRNA stability.
      Interaction of a nucleocytoplasmic protein with a regulatory domain in the 3'
      untranslated region critical for stabilization.
AB  - Expression of the Na(+)-coupled glucose cotransporter SGLT1 is regulated post
      transcriptionally at the level of mRNA stability. We have previously demonstrated
      that cAMP-dependent stabilization of the SGLT1 message was correlated with the
      protein phosphorylation-dependent binding of cytoplasmic proteins to a uridine
      rich sequence (URE) in the 3'-untranslated region (UTR). In the present study,
      the regulatory role of the URE was demonstrated by inserting it into the 3'-UTR
      of a beta-globin reporter minigene under the control of the tetracycline
      regulated promoter. The resultant chimeric globin/SGLT1 mRNA expressed after
      transfection into LLC-PK1 cells exhibited a decreased half-life compared with the
      beta-globin control, indicating that the URE serves a destabilizing function.
      Activation of protein kinase A stabilized the chimeric message but not the beta
      globin control, indicating the presence of a regulatory stabilizing sequence
      within the URE. A 38-kDa nucleocytoplasmic protein was identified that recognized
      a 12-nucleotide binding site within the URE. A mutation in this binding site that
      prevented protein binding assayed in vitro by UV cross-linking also prevented
      protein kinase A-dependent stabilization of the chimeric message assayed in vivo.
      These findings identify the interaction between a 38-kDa nucleocytoplasmic
      protein and a regulatory uridine-rich sequence in the 3'-UTR as critical for cAMP
      mediated SGLT1 message stabilization.

PMID- 10950956
TI  - Identification and characterization of an equilibrium intermediate in the
      unfolding pathway of an all beta-barrel protein.
AB  - The guanidinium hydrochloride (GdnHCl)-induced unfolding of an all beta-sheet
      protein, the human acidic fibroblast growth factor (hFGF-1), is studied using a
      variety of biophysical techniques including multidimensional NMR spectroscopy.
      The unfolding of hFGF-1 in GdnHCl is shown to involve the formation of a stable
      equilibrium intermediate. Size exclusion chromotagraphy using fast protein liquid
      chromatography shows that the intermediate accumulates maximally at 0.96 m
      GdnHCl. 1-Anilinonapthalene 8-sulfonate binding, one-dimensional (1)H NMR, and
      limited proteolytic digestion experiments suggest that the intermediate has
      characteristics resembling a molten globule state. Chemical shift perturbation
      and hydrogen-deuterium exchange monitored by (1)H-(15)N heteronuclear single
      quantum coherence spectra reveal that profound structural changes in the
      intermediate state (in 0.96 m GdnHCl) occur in the C-terminal, heparin binding
      region of the protein molecule. Additionally, results of the stopped flow
      fluorescence experiments suggest that the kinetic refolding of hFGF-1 proceeds
      through the accumulation of an intermediate at low concentrations of the
      denaturant. To our knowledge, the present study is the first report wherein an
      equilibrium intermediate is characterized in detail in an all beta-barrel
      protein.

PMID- 10950957
TI  - Architecture of Ca(2+) channel pore-lining segments revealed by covalent
      modification of substituted cysteines.
AB  - The cysteine accessibility method was used to explore calcium channel pore
      topology. Cysteine mutations were introduced into the SS1-SS2 segments of Motifs
      I-IV of the human cardiac L-type calcium channel, expressed in Xenopus oocytes
      and the current block by methanethiosulfonate compounds was measured. Our studies
      revealed that several consecutive mutants of motifs II and III are accessible to
      methanethiosulfonates, suggesting that these segments exist as random coils.
      Motif I cysteine mutants exhibited an intermittent sensitivity to these
      compounds, providing evidence for a beta-sheet secondary structure. Motif IV
      showed a periodic sensitivity, suggesting the presence of an alpha-helix. These
      studies reveal that the SS1-SS2 segment repeat in each motif have non-uniform
      secondary structures. Thus, the channel architecture evolves as a highly
      distorted 4-fold pore symmetry.

PMID- 10950958
TI  - Phosphatidylinositol 4-phosphate 5-kinase Its3 and calcineurin Ppb1 coordinately
      regulate cytokinesis in fission yeast.
AB  - The ppb1(+) gene encodes a fission yeast homologue of the mammalian calcineurin.
      We have recently shown that Ppb1 is essential for chloride ion homeostasis, and
      acts antagonistically with Pmk1 mitogen-activated protein kinase pathway. In an
      attempt to identify genes that share an essential function with calcineurin, we
      screened for mutations that confer sensitivity to the calcineurin inhibitor FK506
      and high temperature, and isolated a mutant, its3-1. its3(+) was shown to be an
      essential gene encoding a functional homologue of phosphatidylinositol-4
      phosphate 5-kinase (PI(4)P5K). The temperature upshift or addition of FK506
      induced marked disorganization of actin patches and dramatic increase in the
      frequency of septation in the its3-1 mutants but not in the wild-type cells.
      Expression of a green fluorescent protein-tagged Its3 and the phospholipase
      Cdelta pleckstrin homology domain indicated plasma membrane localization of
      PI(4)P5K and phosphatidylinositol 4,5-bisphosphate. These green fluorescent
      protein-tagged proteins were concentrated at the septum of dividing cells, and
      the mutant Its3 was no longer localized to the plasma membrane. These data
      suggest that fission yeast PI(4)P5K Its3 functions coordinately with calcineurin
      and plays a key role in cytokinesis, and that the plasma membrane localization of
      Its3 is the crucial event in cytokinesis.

PMID- 10950959
TI  - A family of secreted mucins from the parasitic nematode Toxocara canis bears
      diverse mucin domains but shares similar flanking six-cysteine repeat motifs.
AB  - Infective larvae of the parasitic nematode Toxocara canis secrete a family of
      mucin-like glycoproteins, which are implicated in parasite immune evasion.
      Analysis of T. canis expressed sequence tags identified a family of four mRNAs
      encoding distinct apomucins (Tc-muc-1-4), one of which had been previously
      identified in the TES-120 family of glycoproteins secreted by this parasite. The
      protein products of all four cDNAs contain signal peptides, a repetitive
      serine/threonine-rich tract, and varying numbers of 36-amino acid six-cysteine
      (SXC) domains. SXC domains are found in many nematode proteins and show
      similarity to cnidarian (sea anemone) toxins. Antibodies to the SXC domains of Tc
      MUC-1 and Tc-MUC-3 recognize differently migrating members of TES-120. TES-120
      proteins separated by chromatographic methods showed distinct amino acid
      composition, mass, and sequence information by both Edman degradation and matrix
      assisted laser desorption ionization/time of flight mass spectrometry on peptide
      fragments. Tc-MUC-1, -2, and -3 were shown to be secreted mucins with real masses
      of 39.7, 47.8, and 45.0 kDa in contrast to their predicted peptide masses of
      15.7, 16.2, and 26.0 kDa, respectively. The presence of SXC domains in all mucin
      products supports the suggestion that the SXC motif is required for mucin
      assembly or export. Homology modeling indicates that the six-cysteine domains of
      the T. canis mucins adopt a similar fold to the sea anemone potassium channel
      blocking toxin BgK, forming three disulfide bonds within each subunit.

PMID- 10950960
TI  - The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding
      domain and binds directly to Sin3A.
AB  - Different mechanisms mediating methylation-dependent repression have been
      demonstrated. Two of these mechanisms play a role in the context of the
      granulocyte/macrophage-specific lysozyme gene: direct interference with DNA
      binding of the transcription factor GA-binding protein and deacetylation of
      histones. Besides enhancement in the unmethylated state, and transcriptional
      repression upon DNA methylation, the lysozyme downstream enhancer confers tissue
      specific demethylation. Because both demethylation activity and repression
      ability have been attributed to the methyl-CpG-binding domain-containing protein
      MBD2, we analyzed this protein. The short form MBD2b binds to the methylated
      lysozyme enhancer and mediates transcriptional repression. MBD2b is capable of
      binding to the transcriptional repressor Sin3A. The interaction domain of Sin3A
      required for binding to MBD2b contains the paired amphipathic helix 3. We
      identified a minimal functional domain that confers both transcriptional
      repression as well as the interaction to Sin3A. In contrast to the functionally
      related proteins MeCP2 and MBD1, the repression domain of MBD2b overlaps with the
      methyl-CpG-binding domain.

PMID- 10950961
TI  - The low molecular mass PsbW protein is involved in the stabilization of the
      dimeric photosystem II complex in Arabidopsis thaliana.
AB  - Arabidopsis thaliana plants have been transformed with an antisense gene to the
      psbW of photosystem II (PSII). Eight transgenic lines containing low levels of
      psbW mRNA have been obtained. Transgenic seedlings with low contents of PsbW
      protein (more than 96% reduced) were selected by Western blotting and used for
      photosynthetic functional studies. There were no distinct differences in
      phenotype between the antisense and wild type plants during vegetative period
      under normal growth light intensities. However, a sucrose gradient separation of
      briefly solubilized thylakoid membranes revealed that no dimeric PSII
      supracomplex could be detected in the transgenic plants lacking the PsbW protein.
      Furthermore, analysis of isolated thylakoids demonstrated that the oxygen
      evolving rate in antisense plants decreased by 50% compared with the wild type.
      This was found to be due to up to 40% of D1 and D2 reaction center proteins of
      PSII disappearing in the transgenic plants. The absence of the PsbW protein also
      altered the contents of other PSII proteins to differing extents. These results
      show that in the absence of the PsbW protein, the stability of the dimeric PSII
      is diminished and consequently the total number of PSII complexes is greatly
      reduced. Thus the nuclear encoded PsbW protein may play a crucial role in the
      biogenesis and regulation of the photosynthetic apparatus.

PMID- 10950962
TI  - NMR structure of the N-terminal J domain of murine polyomavirus T antigens.
      Implications for DnaJ-like domains and for mutations of T antigens.
AB  - The NMR structure of the N-terminal, DnaJ-like domain of murine polyomavirus
      tumor antigens (PyJ) has been determined to high precision, with root mean square
      deviations to the mean structure of 0.38 A for backbone atoms and 0.94 A for all
      heavy atoms of ordered residues 5-41 and 50-69. PyJ possesses a three-helix fold,
      in which anti-parallel helices II and III are bridged by helix I, similar to the
      four-helix fold of the J domains of DnaJ and human DnaJ-1. PyJ differs
      significantly in the lengths of N terminus, helix I, and helix III. The
      universally conserved HPD motif appears to form a His-Pro C-cap of helix II.
      Helix I features a stabilizing Schellman C-cap that is probably conserved
      universally among J domains. On the helix II surface where positive charges of
      other J domains have been implicated in binding of hsp70s, PyJ contains glutamine
      residues. Nonetheless, chimeras that replace the J domain of DnaJ with PyJ
      function like wild-type DnaJ in promoting growth of Escherichia coli. This
      activity can be modulated by mutations of at least one of these glutamines. T
      antigen mutations reported to impair cellular transformation by the virus,
      presumably via interactions with PP2A, cluster in the hydrophobic folding core
      and at the extreme N terminus, remote from the HPD loop.

PMID- 10950963
TI  - Interferon-inducible Myc/STAT-interacting protein Nmi associates with IFP 35 into
      a high molecular mass complex and inhibits proteasome-mediated degradation of IFP
      35.
AB  - Nmi is an interferon (IFN)-inducible protein homologous to IFN-inducible protein
      IFP 35. The homology consists of a novel Nmi/IFP 35 domain (NID) of 90-92 amino
      acids that is repeated in tandem in each protein and mediates Nmi-Nmi protein
      interactions and subcellular localization. In a yeast two-hybrid screen with a
      fragment of Nmi protein containing both NIDs, we identified an interaction
      between Nmi and IFP 35. Deletion derivatives of the proteins indicate that both
      NIDs are required for the interaction between Nmi and IFP 35. In mammalian cells,
      Nmi and IFP 35 co-immunoprecipitate and co-localize in large cytoplasmic
      speckles. Nmi and IFP 35 proteins associate into a high molecular mass complex of
      300-400 kDa as determined by native gel electrophoresis and gel filtration. The
      association of Nmi and IFP 35 into a complex can be demonstrated in multiple cell
      lines and is not dependent on treatment with IFN. Short term and long term
      cultures of transfected HEK293 cells suggest that Nmi and IFP 35 proteins
      stabilize each other through complex formation. IFP 35 appears to be more labile
      because Nmi was stable in the absence of IFP 35, whereas IFP 35 was degraded in
      the absence of Nmi. A deletion analysis revealed that Nmi must interact with IFP
      35 to prevent its degradation and that the amino terminus of Nmi is required, but
      not sufficient, for this function. Inhibition of the proteasome, but not other
      proteases, led to increased levels of IFP 35. Thus, we have shown that Nmi and
      IFP 35 associate into a protein complex, that IFP 35 is degraded in a proteasome
      mediated process, and that a novel function of Nmi is to prevent IFP 35
      degradation. The stabilization of IFP 35 by Nmi may serve to amplify the
      physiologic effects of IFNs.

PMID- 10950965
TI  - Heme insertion, assembly, and activation of apo-neuronal nitric-oxide synthase in
      vitro.
AB  - It has been established that in the case of inducible NO synthase (NOS), a
      functionally active homodimer is assembled from the heme-deficient monomeric apo
      NOS in vitro by the addition of heme, whereas the heme-deficient neuronal isoform
      (apo-nNOS) is at best only partially activated. In the current study we have
      discovered that reactive oxygen species, which can be removed by the addition of
      superoxide dismutase and catalase, destroy the heme and limit the activation of
      apo-nNOS in vitro. With the use of these improved conditions, we show for the
      first time that heme insertion is a rapid process that results in formation of a
      heme-bound monomeric nNOS that is able to form the ferrous-CO P450 complex but is
      unable to synthesize NO. A slow process requiring more than 90 min is required
      for dimerization and activation of this P450 intermediate to give an enzyme with
      a specific activity of approximately 1100 nmol of NO formed/min/mg of protein,
      similar to that of the native enzyme. Interestingly, the dimer is not SDS
      resistant and is not the same dimer that forms in vivo. These studies indicate at
      least two intermediates in the assembly of nNOS and advance our understanding of
      the regulation of nNOS.

PMID- 10950966
TI  - Restricted passage of reaction intermediates through the ammonia tunnel of
      carbamoyl phosphate synthetase.
AB  - The x-ray crystal structure of the heterodimeric carbamoyl phosphate synthetase
      from Escherichia coli has identified an intermolecular tunnel that connects the
      glutamine binding site within the small amidotransferase subunit to the two
      phosphorylation sites within the large synthetase subunit. The tunneling of the
      ammonia intermediate through the interior of the protein has been proposed as a
      mechanism for the delivery of the ammonia from the small subunit to the large
      subunit. A series of mutants created within the ammonia tunnel were prepared by
      the placement of a constriction via site-directed mutagenesis. The degree of
      constriction within the ammonia tunnel of these enzymes was found to correlate to
      the extent of the uncoupling of the partial reactions, the diminution of
      carbamoyl phosphate formation, and the percentage of the internally derived
      ammonia that is channeled through the ammonia tunnel. NMR spectroscopy and a
      radiolabeled probe were used to detect and identify the enzymatic synthesis of N
      amino carbamoyl phosphate and N-hydroxy carbamoyl phosphate from hydroxylamine
      and hydrazine. The kinetic results indicate that hydroxylamine, derived from the
      hydrolysis of gamma-glutamyl hydroxamate, is channeled through the ammonia tunnel
      to the large subunit. Discrimination between the passage of ammonia and
      hydroxylamine was observed among some of these tunnel-impaired enzymes. The
      overall results provide biochemical evidence for the tunneling of ammonia within
      the native carbamoyl phosphate synthetase.

PMID- 10950967
TI  - Identification of critical residues required for suppressor of cytokine signaling
      specific regulation of interleukin-4 signaling.
AB  - Suppressor of cytokine signaling (SOCS) family proteins were originally
      identified as cytokine-induced negative regulators of cytokine signaling. We show
      that SOCS-1 and SOCS-3 inhibit interleukin (IL)-4-dependent signal transducer and
      activator of transcription 6 (Stat6) activation of and subsequent gene induction.
      By contrast, SOCS-2 and cytokine-inducible Src homology domain 2 (SH2)-containing
      protein up-regulate these processes. IL-4 initiates transmembrane signaling
      through two types of receptor complexes comprising the IL-4Ralpha subunit and the
      associated Janus kinase 1 (Jak1) as common essential components. We demonstrate
      that both SOCS-1- and SOCS-3-mediated down-regulation of IL-4 signaling is due to
      an inhibition of the receptor associated Jak1 activity. The SOCS proteins contain
      an amino-terminal region of variable length and primary structure, a central SH2
      domain, and a carboxyl-terminal conserved motif termed SOCS-box. We show that the
      SH2 domains of SOCS-2, SOCS-3, and cytokine-inducible SH2-containing protein are
      functionally redundant in regulating the IL-4-dependent Jak-Stat signaling. The
      Pre-SH2 domains of SOCS-2 and SOCS-3 confer the specificity of their regulatory
      function. Importantly, the Pre-SH2 domain of SOCS-3 alone can inhibit IL-4
      signaling. The SH2-proximal 25 amino acids of SOCS-3 are sufficient for this
      inhibition, and the Thr residue at position 24 and the Phe residue at position 25
      are individually indispensable for its inhibitory function. Thus, the Thr-Phe
      motif in the Pre-SH2 domain plays a critical role in SOCS-3-mediated inhibition
      of the IL-4-dependent Jak-Stat signaling, likely by regulating the mode of SOCS
      Jak interaction.

PMID- 10950968
TI  - Epidemiology of Borna disease virus.

PMID- 10950969
TI  - Vaccination of cattle with attenuated rinderpest virus stimulates CD4(+) T cell
      responses with broad viral antigen specificity.
AB  - The immune responses of cattle inoculated with either a virulent or an attenuated
      vaccine strain of rinderpest virus (RPV) were examined by measuring the
      proliferation of peripheral blood mononuclear cells (PBMC) to whole RPV antigen
      preparations and to individual RPV major structural proteins expressed using
      recombinant adenoviruses. Responses to the T cell mitogen concanavalin A (ConA)
      were also measured as a control to monitor non-specific effects of infection with
      RPV on T cell responses. Infection with the vaccine strain of RPV was found to
      induce a strong CD4(+) T cell response. A specific response was detected to all
      RPV proteins tested, namely the haemagglutinin (H), fusion (F), nucleocapsid (N)
      and matrix (M) proteins, in animals vaccinated with the attenuated strain of the
      virus. No one protein was found to be dominant with respect to the induction of T
      cell proliferative responses. As expected, vaccination of cattle with an
      unrelated virus vaccine, a capripox vaccine, failed to produce a response to RPV
      antigens. While profound suppression of T cell responses was observed following
      infection with the virulent strain of RPV, no evidence of impairment of T cell
      responsiveness was observed following RPV vaccination, or on subsequent challenge
      of vaccinated animals with virulent virus.

PMID- 10950970
TI  - Spread and pathogenic characteristics of a G-deficient rabies virus recombinant:
      an in vitro and in vivo study.
AB  - Rabies virus (RV), a highly neurotropic enveloped virus, is known to spread
      within the CNS by means of axonal transport. Although the envelope spike
      glycoprotein (G) of cell-free virions is required for attachment to neuronal
      receptors and for virus entry, its necessity for transsynaptic spread remains
      controversial. In this work, a G gene-deficient recombinant RV (SAD delta G)
      complemented phenotypically with RV G protein (SAD delta G+G) has been used to
      demonstrate the absolute requirement for G in virus transfer from one neuron to
      another, both in vitro, in neuronal cell cultures (cell line and primary
      cultures), and in vivo, in murine animal models. By using a model of stereotaxic
      inoculation into the rat striatum, infection is shown to be restricted to
      initially infected cells and not transferred to secondary neurons. In mouse as in
      rat models of infection, the limited infection did not cause any detectable
      symptoms, suggesting that G-deficient RV recombinants might be valuable as non
      pathogenic, single-round vectors for expression of foreign genes.

PMID- 10950971
TI  - Differential induction of cellular detachment by envelope glycoproteins of
      Marburg and Ebola (Zaire) viruses.
AB  - Human infection by Marburg (MBG) or Ebola (EBO) virus is associated with fatal
      haemorrhagic fevers. While these filoviruses may both incite disease as a result
      of explosive virus replication, we hypothesized that expression of individual
      viral gene products, such as the envelope glycoprotein (GP), may directly alter
      target cells and contribute to pathogenesis. We found that expression of EBO GP
      in 293T cells caused significant levels of cellular detachment in the absence of
      cell death or virus replication. This detachment was induced most potently by
      membrane-bound EBO GP, rather than the shed glycoprotein products (sGP or GP1),
      and was largely attributable to a domain within the extracellular region of GP2.
      Furthermore, detachment was blocked by the Ser/Thr kinase inhibitor 2
      aminopurine, suggesting the importance of a phosphorylation-dependent signalling
      cascade in inducing detachment. Since MBG GP did not induce similar cellular
      detachment, MBG and EBO GP interact with target cells by distinct processes to
      elicit cellular dysregulation.

PMID- 10950972
TI  - Pathogen-specific resistance to Rift Valley fever virus infection is induced in
      mosquito cells by expression of the recombinant nucleoprotein but not NSs non
      structural protein sequences.
AB  - Rift Valley fever virus (RVFV) is an arbovirus of the BUNYAVIRIDAE: family,
      causing recurrent disease outbreaks in Africa. Natural vertebrate hosts include
      cattle and humans. Several mosquito species belonging to the AEDES: and CULEX:
      genera act as vectors of this phlebovirus. To test whether pathogen-derived
      resistance against RVFV could be induced by expressing genomic sequences in
      mosquito cells, as has been shown for La Crosse and dengue 2 viruses, we
      generated various recombinant Semliki Forest viruses expressing the S segment (or
      its genes) in the genomic or antigenomic sense. Expression of the N but not the
      NSs gene interfered with the production of RVFV in mosquito cells and this
      phenomenon was RNA- but not protein-dependent. These results raise questions on
      the molecular mechanisms involved in virus resistance.

PMID- 10950973
TI  - N-glycans on the short ectodomain of the primary envelope glycoprotein play a
      major role in the polyclonal activation of B cells by lactate dehydrogenase
      elevating virus.
AB  - The common biologically cloned isolates of lactate dehydrogenase-elevating virus
      (LDV-P and LDV-vx) invariably cause a polyclonal activation of B cells in
      immunocompetent mice. It is recognized by an at least 10-fold increase in plasma
      IgG2a levels and the de novo formation of immune complexes that most likely
      consist of autoantibodies and their antigens. The present study indicates that
      three closely spaced N-glycans on the short ectodomain of the primary envelope
      glycoprotein, VP-3P, of LDV-P/vx, play a major role in inducing the polyclonal
      proliferation of B cells. IFN-gamma then seems to mediate the differentiation of
      the activated B cells to IgG2a-producing plasma cells. These conclusions are
      based on the finding that the IgG2a hypergammaglobulinaemia and immune complex
      formation were much lower in mice that were infected with LDV variants (LDV-C and
      LDV-v) whose VP-3P ectodomains lack two of the three N-glycans than in LDV-P/vx
      infected mice. In contrast, the VP-3P ectodomains of three neutralization escape
      variants of LDV-C/v whose VP-3P ectodomains possess three N-glycosylation sites
      caused a polyclonal activation of B cells comparable to that of LDV-P/vx.

PMID- 10950974
TI  - Manifestation of thrombocytopenia in dengue-2-virus-infected mice.
AB  - Dengue virus infection causes dengue fever, dengue haemorrhagic fever and dengue
      shock syndrome. No animal model is available that mimics these clinical
      manifestations. In this study, the establishment is reported of a murine model
      for dengue virus infection that resembles the thrombocytopenia manifestation.
      Dengue-2 virus (dengue virus type 2) can infect murine cells either in vitro
      (primary cell culture) or in vivo. Viraemia detected by RT-PCR was found
      transiently at 2 days after intravenous injection of dengue-2 virus. Transient
      thrombocytopenia developed at 10-13 days after primary or secondary infection.
      Anti-platelet antibody was generated after dengue-2 virus infection. There was
      strain variation in dengue-2 virus infection; the A/J strain was more sensitive
      than BALB/c or B6 mice. This dengue-2-virus-infected mouse system accompanied by
      thrombocytopenia and anti-platelet antibody will be a valuable model to study the
      pathogenicity of dengue virus infection.

PMID- 10950975
TI  - Processing of GB virus B non-structural proteins in cultured cells requires both
      NS3 protease and NS4A cofactor.
AB  - The identification of antivirals and vaccines against hepatitis C virus (HCV)
      infection is hampered by the lack of convenient animal models. The need to
      develop surrogate models has recently drawn attention to GB virus B (GBV-B),
      which produces hepatitis in small primates. In a previous study in vitro, it was
      shown that GBV-B NS3 protease shares substrate specificity with the HCV enzyme,
      known to be crucial for virus replication. In this report, GBV-B NS3 activity on
      GBV-B precursor proteins has been analysed in a cell-based system. It is shown
      that mature protein products are obtained that are compatible with the cleavage
      sites proposed on the basis of sequence homology with HCV and that GBV-B NS4A
      protein is required as a cofactor for optimal enzymatic activity. Experiments in
      vitro supported by a structural model mapped the region of NS4A that interacts
      with NS3 and showed that the GBV-B cofactor cannot be substituted for by its HCV
      analogue.

PMID- 10950976
TI  - Characterization of the equine infectious anaemia virus S2 protein.
AB  - S2 is an accessory protein of equine infectious anaemia virus (EIAV), the
      function of which is unknown. In order to gain insight into the function of S2,
      the intracellular localization of the protein, its interaction with viral
      proteins and its incorporation into viral particles have been investigated.
      Immunolocalization of S2 revealed punctate staining in the cytoplasm and the S2
      protein co-precipitated with the EIAV Gag precursor. Despite overexpression of S2
      through the use of a codon-optimized sequence, there was no preferential
      association of S2 with EIAV particles. These data suggest that S2 may function to
      organize the Gag protein during particle assembly in the cytoplasm but that it is
      unlikely to be involved in the early stages of the virus life-cycle.

PMID- 10950977
TI  - Effects of stoichiometry of retroviral components on virus production.
AB  - A study was conducted to investigate the effects of increasing the amount of each
      retroviral component on vector production. It was found that, while the
      components of both amphotropic and ecotropic vectors were expressed independently
      of each other in a transient transfection system, increasing the amount of the
      gag/gag-pol component resulted in a decrease in virus titres for the amphotropic
      particles but not ecotropic particles. Analyses of the virus stocks produced
      indicated that the negative effect on titres was closely linked to the
      availability of envelope proteins for virion incorporation. The negative effect
      was not observed for ecotropic particle production in 293T cells, where the
      ecotropic receptor was absent, but was manifested when production was conducted
      in 293/12 cells expressing the ecotropic receptor. This suggested that the
      premature interaction between envelope and receptor in producer cells could limit
      the amount of envelope available for virion incorporation. In designing optimal
      vector production systems it is essential, therefore, to balance the
      concentration of the vector components and to ensure that there is never an
      excess of Gag/Gag-Pol.

PMID- 10950978
TI  - Growth of rotaviruses in continuous human and monkey cell lines that vary in
      their expression of integrins.
AB  - Rotavirus replication occurs in vivo in intestinal epithelial cells. Cell lines
      fully permissive to rotavirus include kidney epithelial (MA104), colonic (Caco-2)
      and hepatic (HepG2) types. Previously, it has been shown that cellular integrins
      alpha 2 beta 1, alpha 4 beta 1 and alpha X beta 2 are involved in rotavirus cell
      entry. As receptor usage is a major determinant of virus tropism, the levels of
      cell surface expression of these integrins have now been investigated by flow
      cytometry on cell lines of human (Caco-2, HepG2, RD, K562) and monkey (MA104, COS
      7) origin in relation to cellular susceptibility to infection with monkey and
      human rotaviruses. Cells supporting any replication of human rotaviruses (RD,
      HepG2, Caco-2, COS-7 and MA104) expressed alpha 2 beta 1 and (when tested) alpha
      X beta 2, whereas the non-permissive K562 cells did not express alpha 2 beta 1,
      alpha 4 beta 1 or alpha X beta 2. Only RD cells expressed alpha 4 beta 1.
      Although SA11 grew to higher titres in RD, HepG2, Caco-2, COS-7 and MA104 cells,
      this virus still replicated at a low level in K562 cells. In all cell lines
      tested, SA11 replicated to higher titres than did human strains, consistent with
      the ability of SA11 to use sialic acids as alternative receptors. Levels of cell
      surface alpha 2 integrin correlated with levels of rotavirus growth. The alpha 2
      integrin relative linear median fluorescence intensity on K562, RD, COS-7, MA104
      and Caco-2 cells correlated linearly with the titre of SA11 produced in these
      cells at 20 h after infection at a multiplicity of 0.1, and the data best fitted
      a sigmoidal dose-response curve (r(2)=1.00, P=0.005). Thus, growth of rotaviruses
      in these cell lines correlates with their surface expression of alpha 2 beta 1
      integrin and is consistent with their expression of alpha X beta 2 and alpha 4
      beta 1 integrins.

PMID- 10950979
TI  - Activation of cellular interferon-responsive genes after infection of human cells
      with herpes simplex virus type 1.
AB  - Previous studies have shown that infection of human fibroblasts with human
      cytomegalovirus (HCMV) results in activation of cellular interferon-responsive
      gene expression. We demonstrate here that infection of human fibroblasts with
      herpes simplex virus type 1 (HSV-1) in the absence of de novo protein synthesis
      also induces the expression of interferon-responsive genes. Five genes tested
      (encoding ISG54, IFI56, ISG15, 9-27 and MxA) were activated by infection with HSV
      1, although the degree of response varied between the individual genes. HSV-1 was
      a less efficient inducer than HCMV. The effect was a consequence of binding of
      the virus particle to the cell surface or of the presence of virion components
      within the infected cell. Induction was mediated by a pathway other than the
      mechanism through which interferon-alpha mediates its effects on cellular gene
      expression.

PMID- 10950980
TI  - Marek's disease virus (MDV) homologues of herpes simplex virus type 1 UL49 (VP22)
      and UL48 (VP16) genes: high-level expression and characterization of MDV-1 VP22
      and VP16.
AB  - Genes UL49 and UL48 of Marek's disease virus 1 (MDV-1) strain RB1B, encoding the
      respective homologues of herpes simplex virus type 1 (HSV-1) genes VP22 and VP16,
      were cloned into a baculovirus vector. Seven anti-VP22 MAbs and one anti-VP16 MAb
      were generated and used to identify the tegument proteins in cells infected
      lytically with MDV-1. The two genes are known to be transcribed as a single
      bicistronic transcript, and the detection of only one of the two proteins (VP22)
      in MSB-1 lymphoma and in chicken embryo skin cells infected with MDV-1 prompted
      the study of the transcription/translation of the UL49-48 sequence in an in vivo
      and in vitro expression system. VP16 was expressed in vitro at detectable levels,
      whereas it could only be detected at a lower level in a more controlled
      environment. It was demonstrated that VP22 is phosphorylated in insect cells and
      possesses the remarkable property of being imported into all cells in a
      monolayer. VP22 localized rapidly and efficiently to nuclei, like its HSV-1
      counterpart. The DNA-binding property of VP22 is also reported and a part of the
      region responsible for this activity was identified between aa 16 and 37 in the N
      terminal region of the protein.

PMID- 10950981
TI  - The potential terminase subunit of human cytomegalovirus, pUL56, is translocated
      into the nucleus by its own nuclear localization signal and interacts with
      importin alpha.
AB  - Human cytomegalovirus (HCMV) DNA-binding protein pUL56 is thought to be involved
      in the cleavage/packaging process of viral DNA and therefore needs to be
      transported into the nucleus. By using indirect immunofluorescence analysis, HCMV
      pUL56 (p130) was found to be localized predominantly in the nucleus of infected
      cells. Solitary expression of wild-type as well as epitope-tagged pUL56 also
      resulted in nuclear distribution after transfection, suggesting the presence of
      an endogenous nuclear localization signal (NLS). Deletion of a carboxy-terminal
      stretch of basic amino acids (aa 816-827) prevented nuclear translocation,
      indicating that the sequence RRVRATRKRPRR of HCMV pUL56 mediates nuclear
      targetting. The signal character of the NLS sequence was demonstrated by
      successful transfer of the NLS to a reporter protein chimera. Furthermore,
      sequential substitutions of pairs of amino acids by alanine in the context of the
      reporter protein as well as substitutions within the full-length pUL56 sequence
      indicated that residues at positions 7 and 8 of the NLS (R and K at positions 822
      and 823 of pUL56) were essential for nuclear translocation. In order to identify
      the transport machinery involved, the potential of pUL56 to bind importin alpha
      (hSRP1 alpha) was examined. Clear evidence of a direct interaction of a carboxy
      terminal portion as well as the NLS of pUL56 with hSRP1 alpha was provided by in
      vitro binding assays. In view of these findings, it is suggested that nuclear
      translocation of HCMV pUL56 is mediated by the importin-dependent pathway.

PMID- 10950983
TI  - The carboxy terminus of the herpesvirus saimiri ORF 57 gene contains domains that
      are required for transactivation and transrepression.
AB  - Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes
      of herpesviruses. We have previously shown that ORF 57 encodes a multifunctional
      protein, responsible for both transactivation and repression of viral gene
      expression at a post-transcriptional level. This suggests that the ORF 57 protein
      shares some functional similarities with the herpes simplex virus IE63/ICP27 and
      Epstein-Barr virus Mta proteins. However, little is known about the functional
      domains responsible for the properties of ORF 57 due to the limited homology
      shared between these proteins. In this report, we have identified the functional
      domains responsible for transactivation and repression by the ORF 57 protein. We
      demonstrate that the carboxy terminus is required for ORF 57 transactivation,
      repression and an intense SC-35 nuclear spotting. This region contains two highly
      conserved motifs amongst its homologues, a zinc finger-like motif and a highly
      hydrophobic domain. We further show that the hydrophobic domain is required for
      transactivation and is also involved in nuclear localization of the ORF 57
      protein, whereas the zinc finger-like domain is required for transactivation,
      repression and the intense SC-35 nuclear spotting.

PMID- 10950982
TI  - Epstein-Barr virus latent membrane protein 2A has no growth-altering effects when
      expressed in differentiating epithelia.
AB  - Previous studies using transgenic mice with B-cell expression of LMP2A
      demonstrated that LMP2A drives B-cell development and survival signal in the
      absence of normal B-cell receptor (BCR) signal transduction. To determine if
      LMP2A may have similar effects in epithelial differentiation, six transgenic
      murine lines were constructed and analysed with LMP2A expression directed to the
      epidermis by a keratin 14 (K14) promoter cassette. LMP2A protein expression was
      verified by immunofluorescence and immunoprecipitation of skin samples using
      LMP2A-specific antibodies. To evaluate the effects of LMP2A expression on
      epidermal differentiation, immunofluorescence and histochemistry were performed
      on tongue and tail samples of transgenic mice and their wild-type littermate
      controls using differentially expressed keratins. The analysis indicated that
      LMP2A does not alter the normal epithelial differentiation program in the
      epithelia of K14-LMP2A transgenic mice.

PMID- 10950984
TI  - An aberrant genotype revealed in recombinant hepatitis B virus strains from
      Vietnam.
AB  - Six genotypes of hepatitis B virus (HBV) have been described. However, relatively
      few complete genomes originating from East Asia, where most of the world's HBV
      carriers live, have been studied. We analysed five complete HBV genomes of
      Vietnamese origin, which in our previous studies had produced atypical genotyping
      patterns. All five strains had HBsAg sequences with markers for serotype adw. In
      phylogenetic tree analysis, two of the genomes clustered with genotype C, and
      three clustered on a separate branch between genotypes A, B and C, suggesting a
      new genotype. However, these three strains showed signs of recombination in
      similarity plot and bootscanning analysis. Phylogenetic tree analysis of two
      segments separately supported recombination between genotype C and a putative new
      genotype (or possibly a subgroup of genotype A). The segment between nt 1801 and
      2865 was clearly of genotype C origin, while the major part of the genome (nt
      2866-1800) was placed on a branch close to genotype A. The findings encourage
      further study of genotypes and recombination in HBV from this geographical
      region.

PMID- 10950985
TI  - Characterization of a highly divergent TT virus genome.
AB  - A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient
      (PM) with acute non-A-E hepatitis. The full-length genome sequence, referred to
      here as PM virus (PMV), was obtained and its relationship to other full or near
      full-length TTV sequences examined. Although it shares a common genomic
      arrangement and short conserved regions, the majority of the genome is extremely
      divergent, displaying an average genetic distance of 0.60 from all other TTV
      sequences. By comparing PMV with TTV genomes representing the most divergent
      types so far described, six major groups can be distinguished. The level of
      genetic diversity seen between these genomes is higher than would be expected
      within a single virus species. Indeed, PMV could be considered the prototype of
      an independent taxonomic group within the Circoviridae: family. A genoprevalence
      study of sera from blood donors and patients with acute hepatitis suggests that
      PMV is rare.

PMID- 10950987
TI  - Cytological and molecular evidence that the whitefly-transmitted cucumber vein
      yellowing virus is a tentative member of the family Potyviridae.
AB  - Cucumber vein yellowing virus (CVYV) is widespread in cucurbits in the Middle
      East. CVYV has filamentous particles and is transmitted by Bemisia tabaci by the
      semi-persistent mode. It has not yet been assigned to a specific genus or family.
      Ultramicroscopic observations revealed numerous cylindrical cytoplasmic
      inclusions in melon and cucumber cells infected by CVYV isolates from Israel and
      Jordan. Depending on the section orientation, the inclusions appeared as
      pinwheels or as bundles. In addition, a 1.9 kb DNA fragment was amplified by RT
      PCR from CVYV-infected plant extracts using primers designed to detect all
      potyvirids. Sequence comparisons with the amplified fragment indicated that CVYV
      is more closely related to Sweet potato mild mottle virus than to any other virus
      in the family Potyviridae: These results suggest that CVYV can be considered as a
      tentative new member of the genus Ipomovirus:, family Potyviridae:

PMID- 10950986
TI  - Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein.
AB  - Porcine circovirus 2 (PCV2), a single-stranded DNA virus associated with post
      weaning multisystemic wasting syndrome of swine, has two potential open reading
      frames, ORF1 and ORF2, greater than 600 nucleotides in length. ORF1 is predicted
      to encode a replication-associated protein (Rep) essential for replication of
      viral DNA, while ORF2 contains a conserved basic amino acid sequence at the N
      terminus resembling that of the major structural protein of chicken anaemia
      virus. Thus far, the structural protein(s) of PCV2 have not been identified. In
      this study, a viral structural protein of 30 kDa was identified in purified PCV2
      particles. ORF2 of PCV2 was cloned into a baculovirus expression vector and the
      gene product was expressed in insect cells. The expressed ORF2 gene product had a
      molecular mass of 30 kDa, similar to that detected in purified virus particles.
      The recombinant ORF2 protein self-assembled to form capsid-like particles when
      viewed by electron microscopy. Antibodies against the ORF2 protein were detected
      in samples of sera obtained from pigs as early as 3 weeks after experimental
      infection with PCV2. These results show that the major structural protein of PCV2
      is encoded by ORF2 and has a molecular mass of 30 kDa.

PMID- 10950988
TI  - Native electrophoresis and Western blot analysis (NEWeB): a method for
      characterization of different forms of potyvirus particles and similar
      nucleoprotein complexes in extracts of infected plant tissues.
AB  - A combination of native electrophoresis and immunodetection (Western blot) was
      used for the characterization of nucleoprotein particles of the potyvirus Plum
      pox virus (PPV). Virus particles were electrophoresed directly from plant
      extracts in agarose or mixed acrylamide-agarose gels under native conditions,
      blotted on nitrocellulose membranes, and characterized with the aid of a coat
      protein-specific antibody. Using this combined methodology, called NEWeB (native
      electrophoresis and Western blotting), we could show that a population of
      particles that differ in their electrophoretic mobility can be detected in
      extracts of Nicotiana benthamiana, that two different strains of PPV can be
      distinguished in double infections of the same plant and that virus particles
      from leaves contain detectable levels of helper component proteinase molecules.
      The potential of the NEWeB method for the study of structure and function of
      virus particles and similar nucleoprotein complexes in single and mixed
      infections is discussed.

PMID- 10950989
TI  - Evidence that resistance in squash mosaic comovirus coat protein-transgenic
      plants is affected by plant developmental stage and enhanced by combination of
      transgenes from different lines.
AB  - Three transgenic lines of squash hemizygous for the coat protein genes of squash
      mosaic virus (SqMV) were shown previously to have resistant (SqMV-127),
      susceptible (SqMV-22) or recovery (SqMV-3) phenotypes. Post-transcriptional gene
      silencing (PTGS) was the underlying mechanism for resistance of SqMV-127. Here,
      experiments conducted to determine the mechanism of the recovery phenotype and
      whether enhanced resistance could be obtained by combining transgenes from
      susceptible and recovery plants are reported. Upper leaves of SqMV-3 plants were
      sampled for Northern analysis at 17, 31 and 45 days after germination (DAG) and a
      proportion of plants were inoculated with SqMV. SqMV-3 plants inoculated at a
      young stage (17 DAG) showed susceptible or recovery phenotypes. However, a number
      of plants inoculated at later developmental stages (31 or 45 DAG) were resistant
      to infection. Resistance of recovery plants was due to PTGS that was activated at
      a later developmental stage, independent of virus infection. Similar results were
      observed with plants grown under field conditions. To investigate the
      interactions of transgenes, progeny of crosses between SqMV-127, -3 and -22 were
      inoculated with SqMV. Progeny with the transgene of line 127 were resistant.
      However, a number of plants with transgenes from the recovery and susceptible
      lines or the self-pollinated recovery line were resistant even when inoculated at
      a young stage. Northern analysis suggested that resistance was due to PTGS. The
      results reveal that the timing of PTGS and consequent resistance of the
      transgenic plants were affected by their developmental stage and the interaction
      of transgene inserts.

PMID- 10950990
TI  - The 3a cell-to-cell movement gene is dispensable for cell-to-cell transmission of
      brome mosaic virus RNA replicons in yeast but retained over 10(45)-fold
      amplification.
AB  - In yeast expressing the RNA replication proteins encoded by brome mosaic virus
      (BMV), B3URA3, a BMV RNA3 derivative that harbours the 3a cell-to-cell movement
      protein gene and the yeast uracil biosynthesis gene URA3, was replicated and
      maintained in 85-95% of progeny at each cell division. Transmission of the B3URA3
      RNA replicon from mother to daughter yeast did not require the 3a gene.
      Nevertheless, even after passaging for 165 cycles of RNA replication and yeast
      cell division, each of 40 independent Ura(+) colonies tested retained B3URA3 RNAs
      whose electrophoretic mobilities and accumulation levels were indistinguishable
      from those of the original B3URA3. These and other results suggest that
      unselected genes in many positive-strand RNA virus replicons can be stably
      retained if the presence of the gene does not confer a selective disadvantage in
      RNA replication.

PMID- 10950991
TI  - Codon usage in nucleopolyhedroviruses.
AB  - Phylogenetic analyses based on baculovirus polyhedrin nucleotide and amino acid
      sequences revealed two major nucleopolyhedrovirus (NPV) clades, designated Group
      I and Group II. Subsequent phylogenetic analyses have revealed three Group II
      subclades, designated A, B and C. Variations in amino acid frequencies determine
      the extent of dissimilarity for divergent but structurally and functionally
      conserved genes and therefore significantly influence the analysis of
      phylogenetic relationships. Hence, it is important to consider variations in
      amino acid codon usage. The Genome Hypothesis postulates that genes in any given
      genome use the same coding pattern with respect to synonymous codons and that
      genes in phylogenetically related species generally show the same pattern of
      codon usage. We have examined codon usage in six genes from six NPVs and found
      that: (1) there is significant variation in codon use by genes within the same
      virus genome; (2) there is significant variation in the codon usage of homologous
      genes encoded by different NPVs; (3) there is no correlation between the level of
      gene expression and codon bias in NPVs; (4) there is no correlation between gene
      length and codon bias in NPVs; and (5) that while codon use bias appears to be
      conserved between viruses that are closely related phylogenetically, the patterns
      of codon usage also appear to be a direct function of the GC-content of the virus
      encoded genes.

PMID- 10950992
TI  - Distribution of prion protein in the ileal Peyer's patch of scrapie-free lambs
      and lambs naturally and experimentally exposed to the scrapie agent.
AB  - A sensitive immunohistochemical procedure was used to investigate the presence of
      prion protein (PrP) in the ileal Peyer's patch of PrP-genotyped lambs, including
      scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie
      agent. The tyramide signal amplification system was used to enhance the
      sensitivity of conventional immunohistochemical procedures to show that PrP was
      widely distributed in the enteric nervous plexus supplying the gut wall. In
      scrapie-free lambs, PrP was also detected in scattered cells in the lamina
      propria and in the dome and interfollicular areas of the Peyer's patch. In the
      follicles, staining for PrP was mainly confined to the capsule and cells
      associated with vascular structures in the light central zone. In lambs naturally
      exposed to the scrapie agent, staining was prominent in the dome and neck region
      of the follicles and was also found to be associated with the follicle-associated
      epithelium. Similar observations were made in lambs that had received a single
      oral dose of scrapie-infected brain material from sheep with a homologous and
      heterologous PrP genotype 1 and 5 weeks previously. These studies show that the
      ileal Peyer's patch in young sheep may be an important site of uptake of the
      scrapie agent and that the biology of this major gut-associated lymphoid tissue
      may influence the susceptibility to oral infection in sheep. Furthermore, these
      studies suggest that homology or heterology between PrP genotypes or the presence
      of PrP genotypes seldom associated with disease does not impede uptake of PrP.

PMID- 10950993
TI  - Phylogeny of the genus flavivirus using complete coding sequences of arthropod
      borne viruses and viruses with no known vector

PMID- 10951091
TI  - Problems and perspectives in studying the biological role of carnosine.
AB  - In describing carnosine among the constituents of muscle tissue in 1900, V.
      Gulevitsch opened the question of its real biological role. Investigation of
      carnosine-related phenomena occurred simultaneously with the study of its
      metabolic transformation within the cell. It has now been demonstrated that
      carnosine has the ability to protect cells against oxidative stress as well as to
      increase their resistance toward functional exhaustion and accumulation of senile
      features. Mechanisms of such protection are explained in terms of proton
      buffering, heavy metal chelating, as well as free radical and active sugar
      molecule scavenging, preventing modification of biomacromolecules and keeping
      their native functional activity under oxidative stress. Several carnosine
      derivatives are characterized by different rates of splitting by tissue
      carnosinase and by different biological efficiencies, thus the biological
      significance of enzymatic modification of carnosine during its tissue metabolism
      may be increased resistance of cells operating under unfavorable conditions.

PMID- 10951092
TI  - Role of histidine-related compounds as intracellular proton buffering
      constituents in vertebrate muscle.
AB  - The intracellular non-bicarbonate buffering capacity of vertebrate muscle is
      mainly supported by the imidazole groups of histidine residues in proteins, free
      L-histidine in some fish species, and histidine-containing dipeptides such as
      carnosine, anserine, and balenine (ophidine). The proton buffering capacity
      markedly differs between muscle types and animal species depending on the ability
      for anaerobic exercise. The capacity is typically high in fast-twitch glycolytic
      muscles of vertebrates adapted for anaerobic performance such as burst swimming
      in fishes, prolonged anoxic diving in marine mammals, flight in birds, sprint
      running in mammalian sprinters, and hopping locomotion in some terrestrial
      mammals. A high correlation between buffering capacity, concentration of
      histidine-related compounds in muscle, and percentage of fast-twitch fibers in
      all vertebrates adapted for intense anaerobic performance clearly supports the
      idea that proton buffering is the main physiological function of histidine
      related compounds.

PMID- 10951093
TI  - A re-evaluation of the antioxidant activity of purified carnosine.
AB  - The antioxidant activity of carnosine has been re-evaluated due to the presence
      of contaminating hydrazine in commercial carnosine preparations. Purified
      carnosine is capable of scavenging peroxyl radicals. Inhibition of the oxidation
      of phosphatidylcholine liposomes by purified carnosine is greater in the presence
      of copper than iron, a phenomenon likely to be due to the copper chelating
      properties of carnosine. Purified carnosine is capable of forming adducts with
      aldehydic lipid oxidation products. Adduct formation is greatest for alpha,beta
      monounsaturated followed by polyunsaturated and saturated aldehydes. While the
      ability of carnosine to form adducts with aldehydic lipid oxidation products is
      lower than other compounds such as glutathione, the higher concentrations of
      carnosine in skeletal muscle are likely to make it the most important molecule
      that forms aldehyde adducts. Monitoring changes in carnosine concentrations in
      oxidizing skeletal muscle shows that carnosine oxidation does not occur until the
      later stages of oxidation suggesting that carnosine may not be as effective free
      radical scavenger in vivo as other antioxidants like alpha-tocopherol.

PMID- 10951095
TI  - Biosynthesis, release, and uptake of carnosine in primary cultures.
AB  - Biosynthesis, release, and uptake of carnosine (beta-alanyl-L-histidine) in
      highly enriched primary cell cultures of skeletal muscle and CNS tissue have been
      investigated. The synthesis is restricted to muscle cells, oligodendrocytes, and
      ensheathing cells of olfactory bulb and increases during differentiation of these
      cells. Astrocytes, in contrast, do not synthesize carnosine but are equipped with
      a dipeptide transporter by which carnosine is taken up very efficiently.

PMID- 10951094
TI  - Carnosine and protein carbonyl groups: a possible relationship.
AB  - Carnosine has been shown to react with low-molecular-weight aldehydes and ketones
      and has been proposed as a naturally occurring anti-glycating agent. It is
      suggested here that carnosine can also react with ("carnosinylate") proteins
      bearing carbonyl groups, and evidence supporting this idea is presented.
      Accumulation of protein carbonyl groups is associated with cellular ageing
      resulting from the effects of reactive oxygen species, reducing sugars, and other
      reactive aldehydes and ketones. Carnosine has been shown to delay senescence and
      promote formation of a more juvenile phenotype in cultured human fibroblasts. It
      is speculated that carnosine may intracellularly suppress the deleterious effects
      of protein carbonyls by reacting with them to form protein-carbonyl-carnosine
      adducts, i.e., "carnosinylated" proteins. Various fates of the carnosinylated
      proteins are discussed including formation of inert lipofuscin and proteolysis
      via proteosome and RAGE activities. It is proposed that the anti-ageing and
      rejuvenating effects of carnosine are more readily explainable by its ability to
      react with protein carbonyls than its well-documented antioxidant activity.

PMID- 10951096
TI  - Carnosine as a regulator of soluble guanylate cyclase.
AB  - The molecular mechanism of the participation of carnosine in the functioning of
      soluble guanylate cyclase is discussed. It is shown that carnosine inhibits the
      activation of soluble guanylate cyclase by sodium nitroprusside and a derivative
      of furoxan--1,2,5-oxadiazolo-trioxide (an NO donor). However, carnosine has no
      effect on stimulation of the enzyme by a structural analog of the latter
      compound, a furazan derivative (1,2,5-oxadiazolo-dioxide) that is not an NO
      donor; nor was carnosine involved in the enzyme activation by protoporphyrin IX,
      whose stimulatory effect is not associated with the guanylate cyclase heme. The
      inhibition by carnosine of guanylate cyclase activation by an NO donor is due to
      the interaction of carnosine with heme iron with subsequent formation of a
      chelate complex. It was first demonstrated that carnosine is a selective
      inhibitor of NO-dependent activation of guanylate cyclase and may be used for
      suppression of activity of the intracellular signaling system NO-soluble
      guanylate cyclase-cGMP, whose sharp increase is observed in malignant tumors,
      sepsis, septic shock, asthma, and migraine.

PMID- 10951097
TI  - Metal complexes of carnosine.
AB  - The ligand properties of carnosine are analyzed. The stoichiometry, stability
      constants, and structural and spectroscopic characteristics of its coordination
      compounds with transition and representative metal cations are discussed. Mixed
      ligand systems containing carnosine are also presented. The biological activity
      of some of these metallic complexes is briefly considered.

PMID- 10951098
TI  - Vascular smooth muscle actions of carnosine as its zinc complex are mediated by
      histamine H(1) and H(2) receptors.
AB  - The endogenous dipeptide carnosine (beta-alanyl-L-histidine), at 0.1-10 mM, can
      provoke sustained contractures n rabbit saphenous vein rings with greater
      efficacy than noradrenaline. The effects are specific; anserine and homocarnosine
      are ineffective, as are carnosine's constituent amino acids histidine and beta
      alanine. Zinc ions enhance the maximum carnosine-induced tension (to 127 +/- 13%
      of control at 10 microM Zn(total)) and muscle sensitivity is potentiated (mean
      K(0.5) reduced from 1.23 mM to 17 microM carnosine with 15 microM Zn(total)). The
      dipeptide acts as a Zn-carnosine complex (Zn. Carn). The effects of carnosine at
      1 microM-10 mM (total) in the presence of 1-100 microM Zn(2+) (total) can be
      described as a unique function of [Zn. Carn] with an apparent K(0.5) for the
      complex of [7.4)(10(-8)] M. Contractures are reduced at low [Ca(2+)], unaffected
      by adrenoceptor antagonists, but can be blocked by antagonists to several
      receptor types. The most specific effect is by mepyramine, the H(1) receptor
      antagonist. With Zn present, carnosine can inhibit the H(1)-specific binding of
      [(3)H]mepyramine to isolated Guinea pig cerebella membranes. This effect of
      carnosine can be described as a function of the concentration of Zn. Carn with an
      apparent IC(50) of 2.45 microM. Like histamine, carnosine evoked an H2-mediated
      (cimetidine-sensitive) relaxation in the presence of mepyramine, but was less
      potent (10.8 +/- 3.1% of initial tension remaining at 10 mM carnosine compared
      with 13.4 +/- 7.5% remaining at 0.1 mM histamine). Preliminary studies with a Zn
      selective fluorescent probe indicate that functionally significant levels of Zn
      can be released from adventitial mast cells that could modulate actions of
      carnosine in the extravascular space as well as those of histamine itself. We
      conclude that carnosine can act at the smooth muscle H(1)-receptor to provoke
      vasoconstriction and that it also has the potential to act at H(1)-receptors in
      the central nervous system. Carnosine's mode of action is virtually unique: a
      vascular muscle receptor apparently transduces the action of a dipeptide in the
      form of a metal chelate. The functional relationship of carnosine with histamine
      and the possible physiological relevance of Zn ions for the activity of both
      agents have not previously been reported.

PMID- 10951099
TI  - Interactions between carnosine and zinc and copper: implications for
      neuromodulation and neuroprotection.
AB  - This review examines interactions in the mammalian central nervous system (CNS)
      between carnosine and the endogenous transition metals zinc and copper. Although
      the relationship between these substances may be applicable to other brain
      regions, the focus is on the olfactory system where these substances may have
      special significance. Carnosine is not only highly concentrated in the olfactory
      system, but it is also contained in neurons (in contrast to glia cells in most of
      the brain) and has many features of a neurotransmitter. Whereas the function of
      carnosine in the CNS is not well understood, we review evidence that suggests
      that it may act as both a neuromodulator and a neuroprotective agent. Although
      zinc and/or copper are found in many neuronal pathways in the brain, the
      concentrations of zinc and copper in the olfactory bulb (the target of afferent
      input from sensory neurons in the nose) are among the highest in the CNS.
      Included in the multitude of physiological roles that zinc and copper play in the
      CNS is modulation of neuronal excitability. However, zinc and copper also have
      been implicated in a variety of neurologic conditions including Alzheimer's
      disease, Parkinson's disease, stroke, and seizures. Here we review the modulatory
      effects that carnosine can have on zinc and copper's abilities to influence
      neuronal excitability and to exert neurotoxic effects in the olfactory system.
      Other aspects of carnosine in the CNS are reviewed elsewhere in this issue.

PMID- 10951100
TI  - Applicability of zinc complex of L-carnosine for medical use.
AB  - Zinc complex of L-carnosine (L-CAZ; generic name Polaprezinc) is the first drug
      for oral administration in which zinc plays an essential role. L-CAZ was approved
      as an anti-ulcer drug of membrane protection type. Characterization of L-CAZ was
      achieved by various spectroscopic methods along with elemental analysis. Zinc ion
      coordinates with L-carnosine to form a quadridentate 1:1 complex of polymeric
      nature in order to maintain low strain of chelate rings. L-CAZ can remain in
      stomach juice without rapid dissociation and adhere to ulcerous lesion
      specifically, after which L-carnosine and zinc are released to heal the ulcer. L
      CAZ exhibited high efficacy in clinical use without any serious side effect. L
      CAZ exhibited an inhibitory effect on Helicobacter pylori. Physicochemical
      aspects on carnosine, zinc, and zinc complex can explain favorable features of L
      CAZ as a drug.

PMID- 10951101
TI  - Carnosine-related dipeptides in neurons and glia.
AB  - Carnosine-related dipeptides have been demonstrated to occur in the nervous
      tissue of many vertebrates, including humans. Although several hypotheses have
      been formulated, to date their precise physiological role in the nervous system
      remains unknown. This article will review the studies on the presence and
      distribution of these dipeptides in the nervous system of different classes of
      vertebrates. It will focus on the most recent data on their cellular localization
      and potential functions in mammals. The studies on localization of carnosine
      related dipeptides show a complex pattern of expression that involves both
      neuronal and glial cell types. The glial localization, widely distributed
      throughout the whole brain and spinal cord, includes a subset of both mature
      astrocytes and oligodendrocytes, whereas the neuronal localization is restricted
      to a particular type of neurons (the olfactory receptor neurons), and to
      restricted populations of putative migrating neurons and neuroblasts. There is no
      definitive demonstration of the function of these dipeptides in the various cell
      types. However, a wide array of evidence suggests that carnosine-related
      dipeptides could act as natural protective agents. Moreover, recent studies have
      suggested that, as previously postulated for the olfactory receptor neurons, in
      mature functional glial cells as well, carnosine-related dipeptides could be
      implicated in a neuromodulatory functional mechanism.

PMID- 10951102
TI  - Discrimination between apoptosis and necrosis of neurons under oxidative stress.
AB  - Flow cytometric studies of rat cerebellum neurons are described under conditions
      inducing cell death. Using a double labeling technique, discrimination between
      apoptotic and necrotic cell transformations is demonstrated. Histidine containing
      neuropeptides were found to regulate cell stability, taking part in selection of
      the preferable way of neuronal death under oxidative stress.

PMID- 10951103
TI  - A role for carnosine in cellular maintenance.
AB  - The dipeptide L-carnosine has beneficial effects on cultured human fibroblasts.
      Physiological concentrations in standard media prolong their in vitro lifespan
      and strongly reduce the normal features of senescence. Late passage cells in
      normal medium are rejuvenated when transferred to medium containing carnosine,
      and become senescent when carnosine is removed. In the absence of pyruvate,
      carnosine is cytotoxic to neoplastic and transformed human and rodent cells. None
      of these effects are seen with its optical isomer, D-carnosine.

PMID- 10951104
TI  - Anti-ischemic activity of carnosine.
AB  - This review summarizes the data on anti-ischemic activity of carnosine. The
      pronounced anti-ischemic effects of carnosine in the brain and heart are due to
      the combination of antioxidant and membrane-protecting activity, proton buffering
      capacity, formation of complexes with transition metals, and regulation of
      macrophage function. In experimental cerebral ischemia, carnosine decreases
      mortality and is beneficial for neurological conditions of the animals. In
      cardiac ischemia, carnosine protects cardiomyocytes from damage and improves
      contractility of the heart. The data indicate that carnosine can be used as an
      anti-ischemic drug.

PMID- 10951105
TI  - Cardiovascular effects of carnosine.
AB  - Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide found in various
      cells at millimolar concentration with its specific function(s) largely unknown.
      Our interests in therapeutic peptides led to the discovery that carnosine
      dramatically increases contractility when perfused into isolated rat hearts.
      Carnosine's effects are not mediated by histaminic or beta-adrenergic receptors
      or by increasing cyclic AMP, but carnosine does cause a rise in myoplasmic Ca(2+)
      concentration. In chemically skinned cardiac cells, carnosine releases calcium,
      produces contracture, and alters the contractile protein's tension response to
      calcium. Carnosine also acts directly on the ryanodine receptor calcium release
      channel producing large increases in open state probability and dwelltime. In
      this manuscript, we will review studies which provide a basis for considering
      carnosine a modulator of calcium-regulated proteins in cardiac muscle cells and
      consequently an important determinant of contractility and cardiac function.

PMID- 10951106
TI  - The roles of carnosine in aging of skeletal muscle and in neuromuscular diseases.
AB  - Skeletal muscles undergo specific alterations that are related to the aging
      process. The incidence of several neuromuscular diseases (e.g., amyotrophic
      lateral sclerosis (ALS), myasthenia gravis, polymyositis, drug-induced
      myopathies, late-onset mitochondrial myopathy) is age-related. The increased
      sensitivity to disease of aging muscle represents an additional age-related
      negative influence in the presence of existing risk factors (such as a genetic
      predisposition). The potential significance of carnosine lies on one hand in its
      possible influence on specific physiological changes in muscle associated with
      the aging process, and on the other in its effect on oxidative stress and the
      antioxidative system in specific neuromuscular diseases such as ALS or
      polymyositis.

PMID- 10951107
TI  - Carnosine as a potential anti-senescence drug.
AB  - The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) has been
      found to exert an anti-senescence effect when used as a dietary supplement.
      Carnosine clearly improved the external appearance of experimental animals and
      provided beneficial physiological effects, thus maintaining the animals in better
      condition than control animals receiving no carnosine or a mixture of beta
      alanine and L-histidine.

PMID- 10951108
TI  - Use of carnosine as a natural anti-senescence drug for human beings.
AB  - Carnosine is an endogenous free-radical scavenger. The latest research has
      indicated that apart from the function of protecting cells from oxidation-induced
      stress damage, carnosine appears to be able to extend the lifespan of cultured
      cells, rejuvenate senescent cells, inhibit the toxic effects of amyloid peptide
      (A beta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of
      proteins and protein-DNA and protein-protein cross-linking, and maintain cellular
      homeostasis. Also, carnosine seems to delay the impairment of eyesight with
      aging, effectively preventing and treating senile cataract and other age-related
      diseases. Therefore, carnosine may be applied to human being as a drug against
      aging.

PMID- 10951109
TI  - Percutaneous plating in the lower extremity.
AB  - Since the late 1950s, open reduction and internal fixation has been advocated to
      restore bone anatomy and enable early mobilization. This approach often
      necessitated extensive dissection and tissue devitalization, creating an
      environment less favorable for fracture union and more prone to bone infection.
      As a result, other methods, such as intramedullary nailing, have become the
      standard treatment for most diaphyseal fractures of the femur and tibia. However,
      internal fixation with plates and screws remains the treatment of choice for most
      periarticular fractures and other complex fractures inadequately stabilized by
      intramedullary nailing. Recently, more "biologic" methods of reduction involving
      the use of indirect techniques and new plate designs have been developed in an
      attempt to preserve the blood supply to the injured bone, improve the rate of
      fracture healing, decrease the need for bone grafting, and lower the incidence of
      infection and other complications. Percutaneous plating appears to be the next
      step in the evolution of biologic plating. With these techniques, the fracture is
      reduced indirectly, and plates are placed into submuscular or subcutaneous
      tunnels through limited skin incisions. This may result in less surgical trauma
      to tissues and further improvements in clinical results compared with current
      methods of plate insertion.

PMID- 10951110
TI  - Unicameral bone cysts.
AB  - Unicameral, or solitary, bone cysts are unusual tumors seen in the ends of long
      bones in skeletally immature persons. The etiology of these lesions is poorly
      understood. Various hypotheses have included dysplastic processes, synovial
      cysts, and abnormalities in the local circulation. Most patients present with a
      nondisplaced pathologic fracture, but occasionally cysts are found incidentally.
      Plain radiographs typically show a symmetric lesion with cortical thinning and
      expansion of the cortical boundaries. Once diagnosed, unicameral bone cysts
      continue to be a treatment dilemma. Traditional methods, such as prednisolone
      therapy, usually involve multiple anesthetics and injections and are associated
      with high recurrence rates. Major surgical procedures, such as wide exposure,
      curettage, and bone grafting, may be somewhat more effective, but still carry
      with them significant morbidity and recurrence rates. Newer techniques involving
      percutaneous grafting with allograft or bone substitutes or a combination of the
      two are promising in light of their low complication rate and lower reoperation
      rate.

PMID- 10951111
TI  - Acute fractures of the scaphoid.
AB  - Nondisplaced fractures of the scaphoid heal with cast immobilization in most
      cases, but operative treatment is being offered with greater frequency to active
      patients as an approach to reduce the period of cast immobilization. Computed
      tomography is more useful for evaluating displacement than standard radiography.
      Displaced fractures are at greater risk for nonunion and malunion-both of which
      have been associated with the development of radiocarpal arthritis in long-term
      studies--and should therefore be treated operatively. Surgical treatment is also
      recommended for complex fractures (open fractures, perilunate fracture
      dislocations, and scaphoid fractures associated with fracture of the distal
      radius), very proximal fractures, and fractures for which the diagnosis and
      treatment have been delayed. Operative treatment of fractures of the scaphoid has
      been simplified by the development of cannulated screws. Internal fixation of
      fractures of the scaphoid may offer some advantages, including earlier return to
      athletics or manual labor.

PMID- 10951112
TI  - Development dysplasia of the hip from birth to six months.
AB  - The term "developmental dysplasia or dislocation of the hip" (DDH) refers to the
      complete spectrum of abnormalities involving the growing hip, with varied
      expression from dysplasia to subluxation to dislocation of the hip joint. Unlike
      the term "congenital dysplasia or dislocation of the hip," DDH is not restricted
      to congenital problems but also includes developmental problems of the hip. It is
      important to diagnose these conditions early to improve the results of treat-
      ment, decrease the risk of complications, and favorably alter the natural
      history. Careful history taking and physical examination in conjunction with
      advances in imaging techniques, such as ultrasonography, have increased the
      ability to diagnose and manage DDH. Use of the Pavlik harness has become the
      mainstay of initial treatment for the infant who has not yet begun to stand. If
      stable reduction cannot be obtained after 2 weeks of treatment with the Pavlik
      harness, alternative treatment, such as examination of the hip under general
      anesthesia with possible closed reduction, is indicated. If concentric reduction
      of the hip cannot be obtained, surgical reduction of the dislocated hip is the
      next step. Toward the end of the first year of life, the toddlerTs ability to
      stand and bear weight on the lower extremities, as well as the progressive
      adaptations and soft- tissue contractures associated with the dislocated hip,
      preclude use of the Pavlik harness.

PMID- 10951113
TI  - Peripheral nerve injury and repair.
AB  - Peripheral nerve injuries are common, and there is no easily available formula
      for successful treatment. Incomplete injuries are most frequent. Seddon
      classified nerve injuries into three categories: neurapraxia, axonotmesis, and
      neurotmesis. After complete axonal transection, the neuron undergoes a number of
      degenerative processes, followed by attempts at regeneration. A distal growth
      cone seeks out connections with the degenerated distal fiber. The current
      surgical standard is epineurial repair with nylon suture. To span gaps that
      primary repair cannot bridge without excessive tension, nerve-cable
      interfascicular auto-grafts are employed. Unfortunately, results of nerve repair
      to date have been no better than fair, with only 50% of patients regaining useful
      function. There is much ongoing research regarding pharmacologic agents, immune
      system modulators, enhancing factors, and entubulation chambers. Clinically
      applicable developments from these investigations will continue to improve the
      results of treatment of nerve injuries.

PMID- 10951114
TI  - Complications after treatment of tibial pilon fractures: prevention and
      management strategies.
AB  - Complications after treatment of tibial pilon fractures can occur
      intraoperatively or in the early or late postoperative period. Perioperative
      complications include malreduction, inadequate fixation, and intra-articular
      penetration of hardware, all of which may be minimized by preoperative planning
      and meticulous operative technique. Wound complications can lead to deep
      infection, with potentially catastrophic consequences. The incidence of wound
      complications may be lessened by delaying surgery 5 to 14 days, until the
      posttraumatic swelling has subsided. Temporary fixation with a medial spanning
      external fixator is recommended if definitive internal fixation is delayed.
      Fracture blisters should be left undisturbed until the time of surgery. Incisions
      through blood-filled blisters should be avoided whenever possible. Limited
      incisions to achieve reduction and fixation should be made directly over fracture
      sites, to minimize soft-tissue stripping. An indirect reduction technique
      involving the use of ligamentotaxis and low-profile small-fragment implants that
      minimize tension on the incision should be used. Late complications, such as
      stiffness and posttraumatic arthritis, correlate with the severity of the initial
      injury and the accuracy of reduction. Loss of ankle motion can be minimized by
      early range-of-motion exercise after stable fixation has been achieved.
      Posttraumatic ankle arthrosis should be initially treated with anti-inflammatory
      medication, activity modification, and walking aids. Symptomatic patients often
      require an ankle arthrodesis.

PMID- 10951115
TI  - Olecranon fractures: treatment options.
AB  - Fractures of the olecranon process of the ulna typically occur as a result of a
      motor-vehicle or motorcycle accident, a fall, or assault. Nondisplaced fractures
      can be treated with a short period of immobilization followed by gradually
      increasing range of motion. Open reduction and internal fixation is the standard
      treatment for displaced intra-articular fractures. Stable internal fixation with
      figure-of-eight tension-band wire fixation for simple transverse fractures allows
      early motion to minimize stiffness. Use of two knots produces symmetric tension
      at the fracture site and provides more rigid fixation than a single knot. Care
      should be taken to ensure that the tension-band wire and the proximal ends of the
      Kirschner wires are positioned deep to the triceps fibers to prevent wire
      migration. If the anterior cortex is engaged, overpenetration of the wires into
      the soft tissues should be avoided. Plate fixation is appropriate for severely
      comminuted fractures, distal fractures involving the coronoid process, oblique
      fractures distal to the midpoint of the trochlear notch, Monteggia fracture
      dislocations of the elbow, and nonunions. For comminuted fractures and nonunions,
      a dorsally applied limited-contact dynamic-compression plate with supplemental
      bone graft should be utilized to support comminuted depressed articular
      fragments. A one-third tubular hook-plate can be used for fractures with a small
      proximal fragment for which additional fixation of the olecranon tip is desired.
      Fragment excision and triceps advancement is appropriate in selected cases in
      which open reduction seems unlikely to be successful, such as in osteoporotic
      elderly patients with severely comminuted fractures.

PMID- 10951117
TI  - Changes in capillary luminal diameter in rat soleus muscle after hind-limb
      suspension.
AB  - This study examined the time course change of the capillary luminal diameter and
      the number of capillaries in the rat soleus muscle during hind-limb suspension.
      Male Wistar rats were divided into 1 and 3 weeks of hind-limb suspension (HS)
      groups (HS-1 and HS-3). The HS groups were compared with age-matched control
      groups. All morphometric parameters with respect to capillary and muscle fibre
      cross-sectional area were determined in perfusion-fixed soleus muscles. After 1
      and 3 weeks of hind-limb suspension, the mean muscle fibre cross-sectional area
      was significantly decreased in HS-1 (-32.0%) and HS-3 (-59.3%) compared with age
      matched control groups. Despite a lower capillary-to-fibre ratio (HS-1, -19.3%;
      HS-3, -21.2%), the capillary density was unchanged in HS-1 and significantly
      increased in HS-3 compared with age-matched control groups. The mean capillary
      luminal diameter was significantly smaller in HS-1 (-19.9%) and HS-3 (-21.9%)
      than in the age-matched control groups. The capillary-to-fibre perimeter ratio
      which indicates the capillary surface area available for gas exchange between
      blood and tissue did not significantly differ between control groups and HS
      groups. In conclusion, the morphometrical adaptations in rat soleus with the
      suspension involved changes in both the capillary luminal diameter and number of
      capillaries, and the change in capillary surface area was proportional to the
      degree of muscle atrophy in HS groups.

PMID- 10951116
TI  - Effect of combined supplementation with vitamin E and alpha-lipoic acid on
      myocardial performance during in vivo ischaemia-reperfusion.
AB  - Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia
      reperfusion (I-R) injury. Recently the combination of the antioxidants vitamin E
      (VE) and alpha-lipoic acid (alpha-LA) has been reported to improve cardiac
      performance and reduce myocardial lipid peroxidation during in vitro I-R. The
      purpose of these experiments was to investigate the effects of VE and alpha-LA
      supplementation on cardiac performance, incidence of dysrhythmias and biochemical
      alterations during an in vivo myocardial I-R insult. Female Sprague-Dawley rats
      (4-months old) were assigned to one of the two dietary treatments: (1) control
      diet (CON) or (2) VE and alpha-LA supplementation (ANTIOXID). The CON diet was
      prepared to meet AIN-93M standards, which contains 75 IU VE kg-1 diet. The
      ANTIOXID diet contained 10 000 IU VE kg(-1) diet and 1.65 g alpha-LA kg(-1) diet.
      After the 14-week feeding period, significant differences (P<0.05) existed in
      mean myocardial VE levels between dietary groups. Animals in each experimental
      group were subjected to an in vivo I-R protocol which included 25 min of left
      anterior coronary artery occlusion followed by 10 min of reperfusion. No group
      differences (P>0.05) existed in cardiac performance (e.g. peak arterial pressure
      or ventricular work) or the incidence of ventricular dysrhythmias during the I-R
      protocol. Following I-R, two markers of lipid peroxidation were lower (P<0.05) in
      the ANTIOXID animals compared with CON. These data indicate that dietary
      supplementation of the antioxidants, VE and alpha-LA do not influence cardiac
      performance or the incidence of dysrhythmias but do decrease lipid peroxidation
      during in vivo I-R in young adult rats.

PMID- 10951118
TI  - Myosin heavy chain mRNA and protein distribution in immobilized rat skeletal
      muscle are not affected by testosterone status.
AB  - The effects of testosterone treatment and gonadectomy on myosin heavy chain (MHC)
      messenger RNA (mRNA) and protein expression after 1 week's immobilization were
      studied in male rat gastrocnemius muscle. In the testosterone-treated group
      silastic testosterone capsules were implanted subcutaneously before
      immobilization. The gonadectomized animals were castrated at 5 weeks of age. One
      group of eugonadal animals served as the immobilized control group, and another
      as the sedentary control group. Immobilization was performed at 9 weeks of age by
      bilateral hindlimb casting. The body and muscle masses, and the amount of type
      IIa MHC mRNA decreased significantly (P<0.01) in the immobilized animals by
      approximately 30, 40 and 50%, respectively, regardless of the serum testosterone
      levels which ranged from 1.1+/- 0.4 to 59+/-14 nmol L(-1). In the immobilized
      testosterone-treated group the proportion of type IIx MHC mRNA increased to 14%
      of the total MHC mRNA (P=0.02, compared with control). The MHC protein
      distribution did not change significantly. There were no significant differences
      in any parameters between the three immobilized groups. In conclusion, neither
      the lack nor excess of testosterone significantly altered the changes caused by
      immobilization. Therefore, it seems that lack of mechanical loading is a far more
      important determinant of MHC expression than the male sex hormone status.

PMID- 10951119
TI  - Distribution of adenosine A1, A2A and A2B receptors in human skeletal muscle.
AB  - Many important physiological functions of skeletal muscle, such as glucose
      uptake, contraction and blood flow, have been proposed to be regulated via the
      action of adenosine on adenosine receptors. The cellular location of adenosine
      receptors in skeletal muscle is however, not known. The present study examined
      the distribution of A1, A2A and A2B adenosine receptors in human skeletal muscle
      using immunohistochemistry. All three receptor types were localized to vascular
      smooth muscle and endothelial cells, only the adenosine A2A and A2B receptors
      were observed in the plasma membrane and cytosol of the skeletal muscle. The
      finding was supported by results from western-blotting analysis. The cytosolic
      staining of the adenosine A2A receptor was slightly more intense in the type I
      muscle fibres, whereas the A2B receptor was almost absent in type I fibres. The
      present findings demonstrate for the first time, direct evidence for the
      existence of A2A and A2B adenosine receptors but absence of the A1 receptor in
      the sarcolemma and cytosol of skeletal muscle cells. The data also show existence
      of all three of the A1, A2A and A2B adenosine receptors in vascular cells of
      skeletal muscle tissue.

PMID- 10951120
TI  - Pro- and macroglycogenolysis in contracting rat skeletal muscle.
AB  - Glycogen is present in skeletal muscle in smaller acid-insoluble proglycogen
      particles and larger acid-soluble macroglycogen particles. The present study was
      designed to investigate the relative contribution of pro- and macroglycogen to
      glycogenolysis during muscle contractions. Rats were subjected to a glycogen
      depleting exercise bout and refed with either a carbohydrate-rich or fat-rich
      diet, resulting in widely different muscle glycogen contents. The following day,
      isolated hindlimbs were perfused and electrically stimulated to contract for 10
      min. Pre- and postcontraction muscle samples of soleus, white and red
      gastrocnemius were analysed for pro- and macroglycogen. Contractions caused
      significant reductions in both pro- and macroglycogen in all glycogen groups and
      muscle types. In glycogen-supercompensated gastrocnemius muscles, the relative
      utilization of macroglycogen was significantly higher than the relative
      utilization of proglycogen. In muscles with normal to low initial glycogen
      contents, proglycogen was much more abundant than macroglycogen and therefore
      contributed more to glycogenolysis in absolute numbers. In conclusion, both
      proglycogen and macroglycogen are suitable substrates during skeletal muscle
      contractions, although macroglycogen, when amply available, seems to be more
      easily broken down. This may provide an explanation for the dependence of the
      glycogenolytic rate on the total muscle glycogen content.

PMID- 10951121
TI  - Diversity of responses of renal cortical and medullary blood flow to
      vasoconstrictors in conscious rabbits.
AB  - The medullary microcirculation receives only about 10% of total renal blood flow,
      but plays a critical role in long-term arterial pressure regulation, so we need
      to better understand its regulation. Although there is evidence that circulating
      and locally acting hormones can differentially affect cortical and medullary
      blood flow in anaesthetized animals, there is little information from studies in
      conscious animals. This study is aimed (i) to develop a method for chronic
      measurement of cortical and medullary blood flow in conscious rabbits, and (ii)
      to test whether renal cortical and medullary blood flow can be differentially
      affected by intravenous (i.v.) infusions of various vasoconstrictor hormones in
      conscious rabbits. At preliminary operations, rabbits were equipped with single
      fibre laser-Doppler flowprobes in the (left) renal cortex and medulla, and
      Transonic flowprobes for measuring cardiac output and renal blood flow.
      Intravenous angiotensin II (300 ng kg(-1) min(-1)), [Phe2,Ile3,Orn8]-vasopressin
      (30 ng kg(-1) min(-1)), noradrenaline (300 ng kg(-1) min(-1)), endothelin-1 (20
      ng kg(-1) min(-1)) and N G-nitro-L-arginine (10 mg kg(-1)) increased mean
      arterial pressure (by 10-45% of baseline) and reduced heart rate (by 16-35%) and
      cardiac output (by 16-45%). Consistent with previous observations in
      anaesthetized rabbits, all treatments except [Phe2,Ile3, Orn8]-vasopressin
      reduced renal blood flow (13-63%) and cortical blood flow (16-47%), but medullary
      blood flow was significantly reduced only by [Phe2,Ile3,Orn8]-vasopressin (41%)
      and N G-nitro-L-arginine (42%). The diversity of these responses of cortical and
      medullary blood flow to i.v. infusions of vasoconstrictors provides further
      evidence for physiological roles of circulating and local hormones in the
      differential regulation of regional kidney blood flow.

PMID- 10951122
TI  - Sex differences in pressure diuresis/natriuresis in rabbits.
AB  - We tested for sex-related differences in the pressure diuresis/natriuresis
      relationships in anaesthetized, renally denervated rabbits, using an
      extracorporeal circuit to perfuse the left kidney with the rabbit's own blood,
      through a series of step-wise increases in renal artery pressure (RAP) (from 65
      to 130 mmHg). Urine flow, sodium excretion, and the fractional excretions of
      sodium and urine increased with increasing RAP, and were greater in male than in
      female rabbits at all levels of RAP-tested. However, these apparent sex-related
      differences in the acute pressure diuresis/natriuresis relationships were not
      reflected in alterations in chronic regulation of mean arterial pressure (MAP).
      Thus, in rabbits on a normal salt diet (0.85 g day(-1)), resting conscious MAP
      was significantly greater in males (87 +/- 3 mmHg) compared with females (77+/-1
      mmHg). Chronically increasing daily salt intake to 4.98 g day(-1) for 28 days had
      no significant effect on resting conscious MAP in either sex. Thus, although our
      observations indicate sex differences, at least under the present experimental
      conditions, in the factors regulating extracellular fluid volume, these do not
      appear to have a major impact in setting the level of MAP in the long term.

PMID- 10951123
TI  - Constitutive nitric oxide synthesis in the kidney--functions at the
      juxtaglomerular apparatus.
AB  - Tubulo-vascular information transfer at the renal juxtaglomerular apparatus (JGA)
      serves to adjust the biosynthesis and release of renin, the key enzyme of the
      renin angiotensin system, and to regulate glomerular arteriolar muscle tone. The
      macula densa serves as a sensor of tubular NaCl. Concentration-dependent salt
      uptake through the Na-K-2Cl cotransporter located in the apical membrane of
      macula densa cells triggers a signal transduction cascade that involves the
      synthesis of nitric oxide (NO) through a type 1 NO synthase (NOS1) which is
      described with respect to its complex mRNA structure and regulatory aspects. The
      anatomical and functional targets of the NO-soluble guanylyl cyclase-cGMP pathway
      at the JGA are reviewed.

PMID- 10951124
TI  - Diurnal variation in circulating leptin is dependent on gender, food intake and
      circulating insulin in mice.
AB  - Leptin is an adipocyte hormone involved in the regulation of energy homeostasis.
      Its circulating levels show a diurnal rhythm with a nocturnal peak. We examined
      the influences of gender, feeding state, and plasma insulin and glucose on the
      diurnal rhythm in normal mice. Plasma was sampled at 4-h interval for 24 h in
      female (n=80) and male (n=80) mice, which were freely fed or fasted. In both
      genders, plasma leptin displayed a diurnal rhythm with a nadir at 8 or 10 AM and
      a nocturnal peak at 10 PM to 2 AM. The nocturnal increase in leptin was higher in
      females (+160+/-18%) than in males (61+/- 16%; P<0.001), completely abolished by
      fasting, and correlated significantly to the diurnal variation in plasma insulin
      both in females (r=0.44, P=0.003) and males (r=0.46, P<0.001). Baseline plasma
      leptin in non-fasted animals were not different between the genders, whereas
      during fasting, the reduction in leptin was more pronounced in males than in
      females, resulting in a higher plasma leptin after fasting in females. Plasma
      insulin was higher in males under non-fasted conditions (P=0.003), but not
      significantly different between genders in fasted animals. In conclusion, plasma
      leptin displays a nocturnal increase in mice, which is more pronounced in female
      mice than in male mice, is completely abolished by fasting and correlates to the
      diurnal variation in circulating insulin. It is suggested that the nocturnal rise
      in leptin shows gender dependency and is caused by the increase in plasma insulin
      caused by food intake.

PMID- 10951125
TI  - The inhibitory effects of allopregnanolone and pregnanolone on the population
      spike, evoked in the rat hippocampal CA1 stratum pyramidale in vitro, can be
      blocked selectively by epiallopregnanolone.
AB  - The progesterone metabolites allopregnanolone (Allo, 3alpha-hydroxy-5alpha
      pregnan-20-one) and pregnanolone (Preg, 3alpha-hydroxy-5beta-pregnan-20-one)
      enhance the gamma-aminobutyric acid (GABA) action through a distinct site on the
      GABAA-receptor. Their 3beta-isomers epiallopregnanolone (Epiallo, 3beta-hydroxy
      5alpha-pregnan-20-one) and epipregnanolone (Epipreg, 3beta-hydroxy-5beta-pregnan
      20-one), do not have these effects on GABAA-receptors. We have studied the
      interaction between Allo/Preg and their 3beta-isomers on action potentials in rat
      hippocampal slices in vitro. The Schaffer collaterals were stimulated
      electrically in CA1 striatum radiatum and the population spike (POPSP) was
      recorded in stratum pyramidale. A 0.5-nL droplet of drug was applied locally onto
      stratum oriens-pyramidale via a pressure pipett. Muscimol (Mus) (12.5 fmol), Allo
      and Preg (6.25 fmol) caused a reversible inhibition of POPSP. On the other hand,
      6.25 fmol Epiallo had no significant effect on POPSP compared with the vehicle
      control. Combined Epiallo and Allo application caused a dose-dependent reduction
      of the Allo inhibition of POPSP. A full blockage was seen at a molar ratio of
      1:1. Epiallo also blocked the Preg inhibition of POPSP, when the two drugs were
      combined in a molar ratio of 1:1. Epiallo did not block the Mus inhibition of
      POPSP, when the two drugs were combined at a molar ratio of 1:2. Bath perfusion
      of 12.5 microM Epiallo blocked the inhibition of 6.25 fmol Allo on POPSP, but not
      the inhibition caused by 12.5 fmol Mus. Epipreg did not block the inhibition of
      Allo and Preg on POPSP, when it was combined with the two latter drugs at a molar
      ratio of 1:1. Our data suggest that the steroid modulation of the GABAA
      transmitted inhibition of the CA1 pyramidal neurones is selectively and dose
      dependently blocked by Epiallo, the 3beta-hydroxy-isomer of Allo, but not by
      Epipreg, the 3beta-hydroxy-isomer of Preg.

PMID- 10951126
TI  - Free radical generation and oxidative stress with ageing and exercise:
      differential effects in the myocardium and liver.
AB  - Reactive oxygen species and other oxidants are implicated in the mechanisms of
      biological ageing and exercise-induced tissue damage. The present study examined
      the effects of ageing and an acute bout of exercise on intracellular oxidant
      generation, lipid peroxidation, protein oxidation and glutathione (GSH) status in
      the heart and liver of young adult (8 month, N=24) and old (24 month, N=24) male
      Fischer 344 rats. Young rats ran on treadmill at 25 m min-1, 5% grade until
      exhaustion (55.4+/-2.7 min), whereas old rats ran at 15 m min-1, 5% until
      exhaustion (58.0+/-2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an
      indication of intracellular oxidant production, was significantly higher in the
      homogenates of aged heart and liver compared with their young counterparts. In
      the isolated heart and liver mitochondria, ageing increased oxidant production by
      29 and 32% (P<0.05), respectively. Acute exercise increased oxidant production in
      the aged heart but not in the liver. When nicodinamide dinucleotide phosphate
      (reduced), adenosine diphosphate and Fe3+ were included in the assay, DCFH
      oxidation rate was 47 and 34% higher (P<0.05) in the aged heart and liver
      homogenates, respectively, than the young ones. The age differences in the
      induced state reached 83 and 140% (P<0.01) in isolated heart and liver
      mitochondria, respectively. Lipid peroxidation was increased in the aged liver
      and exercised aged heart, whereas protein carbonyl content was elevated only in
      the aged heart (P<0.05). Although our data using DCFH method probably
      underestimated cellular oxidant production because of time delay and antioxidant
      competition, it is clear that oxidative stress was enhanced in both heart and
      liver with old age. Furthermore, aged myocardium showed greater susceptibility to
      oxidative stress after heavy exercise.

PMID- 10951127
TI  - Towards a better understanding of pemphigus autoimmunity.

PMID- 10951128
TI  - Identifying a gene for psoriasis on chromosome 6 (Psors1)

PMID- 10951129
TI  - Measuring the improvement in pulsed dye laser treated port wine stains.

PMID- 10951130
TI  - Lasers for the dermatologist.
AB  - This article reviews the current uses of lasers in dermatological practice. It
      outlines safety issues and legislation and attempts to summarize the relevant
      physics and light interactions. The article is divided into sections pertaining
      to selective photothermolysis of structures containing the major skin
      chromophores: haemoglobin, melanin and water. The lasers used and conditions
      treated are discussed with reference to a literature review.

PMID- 10951131
TI  - Serological markers for melanoma.
AB  - We present a review of current literature concerning the significance of
      serological markers in melanoma patients. Results for cytokines, cytokine
      receptors, cell adhesion molecules, S100 protein, melanoma inhibitory activity,
      tissue-specific reverse transcription-polymerase chain reaction, neurone-specific
      enolase, lipid-bound sialic acid and melanin metabolites such as 5-S
      cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid are discussed. For
      most of these substances, serum levels are more pronounced in the more advanced
      stages of disease. Therefore, these markers seem to have no place in the early
      detection of melanoma. On the other hand, sensitivity in the advanced stages of
      disease seems to be < 100%, compromising their use as a new staging procedure.
      Some markers show promising results as a possible prognostic factor in the early
      detection of disease progression or in the prediction of therapy outcome. If
      confirmed by further studies, this could direct future therapeutic strategies and
      could help to select patients who would benefit most from more aggressive
      (adjuvant) therapies. In addition, the study of some of these substances could
      add to the knowledge of tumour biology and immunology.

PMID- 10951132
TI  - Rising levels of serum S100 protein precede other evidence of disease progression
      in patients with malignant melanoma.
AB  - BACKGROUND: Several serum markers may be useful in the detection of metastatic
      melanoma, but none is in routine clinical use. OBJECTIVE: To assess the validity
      of S100 protein as a serum marker of melanoma progression. METHODS: Serum S100
      protein levels were measured in 496 serum samples from 214 melanoma patients,
      using the Sangtec luminescence immunoassay. There were 75 patients with stage 1
      melanoma, 66 initially with stage 2 melanoma, 49 initially with stage 3 melanoma
      and 24 with stage 4 melanoma. RESULTS: Serum S100 protein levels were < 0.2
      microg L-1 in 71 of 75 (95%) stage 1 patients. One patient who had a normal level
      developed local recurrence. Fifty-eight of 66 (88%) stage 2 patients also had
      normal serum S100 protein levels. One with elevated levels progressed to stage 3
      melanoma and five with elevated levels progressed to stage 4 disease. The
      remaining two with elevated serum S100 protein remained well. Thirty-five of 49
      (71%) stage 3 patients had normal levels and, of these, two have progressed to
      stage 4 disease. Three patients with stage 3 disease had an elevated serum S100
      protein level on one occasion but remained well. Eleven of 13 patients who
      developed stage 4 melanoma during the study had rising levels of serum S100
      protein > 0.2 microg L-1 5-23 weeks before detection of melanoma progression by
      conventional means. Twenty-two of 24 patients with stage 4 disease throughout the
      study had consistently elevated serum S100 protein levels, and the two patients
      with normal levels were clinically disease free after surgery and chemotherapy.
      None of 14 control subjects with atypical naevi had elevated S100 protein levels,
      and only one of 11 healthy normal controls had an elevated level. CONCLUSIONS:
      Thus, rising levels of serum S100 protein are a specific and sensitive clinically
      relevant marker of tumour progression in melanoma patients, which precedes other
      evidence of melanoma recurrence.

PMID- 10951133
TI  - Acral cutaneous melanoma in caucasians: clinical features, histopathology and
      prognosis in 112 patients.
AB  - BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth distinct variant of
      cutaneous melanoma. The histological diagnosis and prognosis of ALM are still
      controversial. OBJECTIVES: To review the features of a large series of patients
      with ALM, and confirm the validity of the histological criteria for this type of
      melanoma. METHODS: A collection of 2642 patients with cutaneous melanoma was
      recorded during the period 1986-97, among these 187 were located on acral sites.
      Histological specimens were reviewed in 112 acral melanomas; the following study
      is based on this subgroup. RESULTS: Histological examination revealed acral
      lentiginous melanomas predominantly in palmoplantar and subungual locations
      (60%), while superficial spreading melanomas (SSM) were found mainly on the
      dorsal aspects of hands and feet (30%). Nodular melanomas (NM) (9%) occurred in
      all acral sites. The histological re-examination confirmed the characteristics of
      ALM as described by Reed in 1976. With increasing tumour thickness nesting of
      tumour cells and upward migration to the cornified layer was similarly observed.
      The 5-year survival rate for patients with primary acral melanoma without
      recognizable metastasis was 82%. ALM differed significantly in survival from SSM
      (P = 0.001) and lentigo maligna melanoma (P < 0. 001), but survival rates were
      similar to NM (P = 0.9). CONCLUSIONS: ALM, as diagnosed by current histological
      criteria, occur on the palms, soles and subungual sites, and have a poor
      prognosis.

PMID- 10951134
TI  - Differentiation of common benign pigmented skin lesions from melanoma by high
      resolution ultrasound.
AB  - BACKGROUND: There are potential clinical benefits if non-invasive methods can be
      used to diagnose or exclude melanoma. OBJECTIVES: We investigated high-resolution
      ultrasound (HRU) as a potential non-invasive diagnostic aid for pigmented skin
      lesions. METHODS: Using a 20-MHz ultrasound B-scan imaging system interfaced to a
      computer, we assessed acoustic shadowing and entry echo line enhancement (EEE)
      for 29 basal cell papillomas (BCPs) and 25 melanomas. Acoustic shadowing was
      estimated by the dermal echogenicity ratio (DER), comparing mean echogenicity
      below the lesion with that of adjacent dermis. Histological features were scored
      independently. RESULTS: DER < 3 correctly distinguished melanoma from BCP with
      100% sensitivity and 79% specificity. Specificity increased to 93% if the
      presence of EEE was included as a discriminator. Shadowing correlated most
      significantly with histological extent of hyperkeratosis (P < 0.0001).
      Consequently, this method falsely identified non-keratotic acanthotic BCP (n = 3)
      as melanoma. Highly significant differences between benign naevi (n = 15) and
      melanomas (n = 24) were found. The SD of retrolesional echogenicity was higher
      for naevi than melanomas (P < 0.0001), but such an analysis was poorly specific
      for the diagnosis of melanoma (30%). CONCLUSIONS: Overall, HRU has considerable
      potential as a high-performance screening tool to assist in the discrimination
      between BCP, but not benign naevi, and melanoma. In particular, it may be
      possible to exclude melanoma with 100% certainty in the differentiation of BCP
      from melanoma.

PMID- 10951135
TI  - The role of pattern analysis and the ABCD rule of dermoscopy in the detection of
      histological atypia in melanocytic naevi.
AB  - BACKGROUND: Clinical features of melanocytic naevi correlate poorly with the
      presence, histopathologically, of architectural disorder and cytological atypia,
      making the detection of histological atypia by means of macroscopic appearance
      unreliable. OBJECTIVES: The aim of this study was to investigate the diagnostic
      effectiveness of dermoscopy in the non-invasive detection of histological atypia
      in naevi. METHODS: Observers blinded for histological diagnosis classified a
      series of 168 melanocytic naevi as common or atypical on the basis of their
      clinical features and on their dermoscopic profile. The diagnostic performance of
      both methods compared with the true (histopathological) diagnosis was assessed.
      RESULTS: Dermoscopy using pattern analysis showed better results than clinical
      examination in the non-invasive detection of naevi with architectural disorder
      with or without cytological atypia (diagnostic accuracy 45% vs. 28%). A
      statistically significant difference in the frequency of dermoscopic parameters
      between atypical and common naevi was found for atypical pigment network (39% vs.
      17%, P = 0.001) and dermoscopic regression structures (13% vs. 2%, P = 0.008).
      Dermoscopic features, which best predicted histological atypia in naevi, were
      regression structures (white scar-like areas or peppering), irregular vascular
      pattern and grey-blue areas (positive predictive values 83%, 83% and 73%,
      respectively). In contrast, no statistically significant difference in the mean
      values of the ABCD score between common and atypical naevi was found. The best
      diagnostic performance of dermoscopy by means of the ABCD rule (cut-off point of
      4.0 of total dermoscopy score) was not dissimilar to that of clinical diagnosis
      (diagnostic accuracy 30%). CONCLUSIONS: Dermoscopy by means of pattern analysis
      enhances the diagnostic accuracy of dermatologists in the prediction of
      histological atypia in melanocytic naevi as compared with clinical examination
      alone.

PMID- 10951136
TI  - Cytoplasmic dynein colocalizes with melanosomes in normal human melanocytes.
AB  - BACKGROUND: Melanocytic dendrites consist of a central core of microtubules and a
      subcortical actin network. Several studies provide arguments supporting the
      hypothesis that actin-based and microtubule-based motor proteins co-operate in
      melanosome transport towards the dendrite tips. Melanosomes can move
      bidirectionally along microtubules in vitro, and in murine melanocytes, they move
      towards the cell periphery and back again. Microtubules have a fast-growing plus
      end and a slow-growing minus end. Microtubule-associated motor proteins move
      unidirectionally either towards the plus or towards the minus end. However, it is
      not known which motor protein is responsible for minus end-directed movement of
      melanosomes. OBJECTIVES: We aimed to investigate the in vitro expression of the
      minus end-directed motor protein cytoplasmic dynein in normal human epidermal
      melanocytes, keratinocytes and dermal fibroblasts. METHODS: Reverse transcription
      polymerase chain reaction and Northern blot analysis were used. In addition, an
      attempt to obtain insight into the subcellular localization of cytoplasmic
      dynein, immunofluorescence studies and immunogold electron microscopic studies
      were performed. RESULTS: The three different forms of cytoplasmic dynein heavy
      chain were expressed in all studied skin cells. Immunofluorescence staining
      showed similar punctate distributions for dynein heavy chain 1 and dynein heavy
      chain 2 in melanocytes, with accentuation in the perinuclear area and dendrite
      tips. Double labelling with a melanosome marker showed apparent co-localization
      of both dynein heavy chains 1 and 2 with melanosomes in the perinuclear area and
      dendrite tips. For the dynein intermediate chain of 74 kDa, again a punctate
      staining pattern was seen with intense centrosomal staining. A close association
      of dynein intermediate chain 74 and alpha-tubulin with the melanosome surface was
      detected using immunogold electron microscopy. CONCLUSIONS: The colocalization of
      different subunits of the cytoplasmic dynein complex with melanosomes is
      consistent with the hypothesis that this motor protein supports minus end
      directed melanosome movement along microtubules.

PMID- 10951137
TI  - A comparative study of Fas and Fas-ligand expression during melanoma progression.
AB  - BACKGROUND: Impaired regulation of apoptosis is known to be associated with the
      development of various cancers. Fas receptor (APO-1/CD95) binding to its ligand,
      Fas-ligand (Fas-L), has been shown to trigger apoptosis in various cell types.
      OBJECTIVES: In this study, we examined CD95 and Fas-L expression on primary and
      metastatic melanoma cells from patients to investigate a potential correlation
      between these measures of apoptosis and different disease stages. PATIENTS AND
      METHODS: Primary melanoma cells were obtained after surgical resection from 19
      patients and metastatic cells from fine-needle aspiration of lymph nodes or
      palpable subcutaneous lesions in 25 patients. Normal skin cells were obtained at
      skin biopsy of 10 healthy donors. RESULTS: Flow cytometric analysis revealed that
      CD95 and Fas-L expression was detected in all the kinds of cell studied. In whole
      cell suspensions, CD95 expression was significantly higher (P < 0.0001) in normal
      skin cells than in melanoma cells, whatever the stage studied. By contrast, we
      observed an increase in Fas-L expression in melanoma cells compared with normal
      ones. Subsequently, using a double staining method, we studied these measures on
      HMB45+ cells, a specific marker for melanoma cells, and found that CD95
      expression was significantly higher (P = 0.0005) in primary than in metastatic
      cells while Fas-L expression was significantly increased (P = 0. 0004) in
      metastatic compared with primary cells. Furthermore, a relationship was found
      between CD95 or Fas-L expression and Breslow thickness; as primary melanoma
      thickness progressively increased, the percentage of HMB45+ CD95+ cells decreased
      while that of HMB45+ Fas-L+ cells concurrently increased. CONCLUSIONS: These
      results suggest that downregulation of CD95 and upregulation of Fas-L in melanoma
      might be considered as concomitant with disease progression.

PMID- 10951138
TI  - Expression of Fas and Fas-ligand in primary cutaneous T-cell lymphoma (CTCL):
      association between lack of Fas expression and aggressive types of CTCL.
AB  - BACKGROUND: Fas (CD95; APO-1) is a transmembrane protein that mediates apoptosis
      upon cross-linking with Fas-ligand (Fas-L). Interaction of Fas-L expressed by
      cytotoxic T cells with Fas-expressing tumour cells plays an important part in
      antitumour immune responses. OBJECTIVES: We aimed to investigate Fas and Fas-L
      expression in frozen and paraffin-embedded material from a large group of
      patients with cutaneous T-cell lymphoma (CTCL). METHODS: Immunostaining with
      monoclonal antibodies against Fas and Fas-L was performed in material from 23
      patients with mycosis fungoides (MF), 10 with lymphomatoid papulosis (LyP), 10
      with CD30-positive primary cutaneous large T-cell lymphoma (LTCL) and nine with
      CD30-negative LTCL. The results were correlated with the type and stage of CTCL
      and clinical features. RESULTS: Expression of Fas by the large majority of the
      neoplastic T cells was observed in 15 of 15 cases of plaque-stage MF, 10 of 10
      cases of LyP and 10 of 10 cases of CD30-positive LTCL, but only in four of 12
      cases of tumour-stage MF and two of nine cases of CD30-negative LTCL. In three of
      four MF patients in whom both plaques and tumours could be studied, a significant
      decrease in Fas expression was observed with progression from plaque-stage to
      tumour-stage disease. Fas-L was expressed by > 50% of the neoplastic T cells in
      46 of 56 biopsies, and no clear relationship with type of CTCL and clinical
      behaviour was observed. CONCLUSIONS: This study demonstrates loss of Fas
      expression in aggressive types of CTCL, but not in indolent types of CTCL. These
      data suggest that loss of Fas receptor expression may be one of the mechanisms
      that allow tumour cells to escape an effective immune response, and may
      contribute to the unfavourable prognosis of some types of CTCL.

PMID- 10951139
TI  - Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary
      cutaneous T- and B-cell lymphomas.
AB  - BACKGROUND: Several studies have investigated the possible involvement of viral
      agents, particularly herpesviruses, in primary cutaneous lymphoma (PCL).
      OBJECTIVES: Our aim was to screen for the presence of human herpesvirus 7 (HHV-7)
      and 8 (HHV-8) genomes in samples of PCL, and to determine if their presence was
      independent of Epstein-Barr virus (EBV). METHODS: Screening was performed using
      polymerase chain reaction assay in 64 skin samples from historical lesional
      tissues with PCL. RESULTS: Only nine cases showed positivity for HHV-7: four of
      29 mycosis fungoides (MF), two of four CD30-positive large-cell cutaneous T-cell
      lymphoma (CTCL), two of 12 follicle centre cutaneous B-cell lymphoma (CBCL) and
      one of nine marginal zone CBCL. Fifteen cases tested positive for EBV: seven of
      29 MF, two of four pleomorphic small/medium sized CTCL, three of three
      angiocentric CTCL, one of 12 follicle centre CBCL and two of nine marginal zone
      CBCL. All cases were uniformly negative for HHV-8. No simultaneous positivity was
      found for EBV and HHV-7. Controls tested negative for all viruses. CONCLUSIONS:
      The findings indicate that EBV, HHV-7 and HHV-8 seem not to be involved in the
      pathogenesis of PCL.

PMID- 10951140
TI  - The A5.1 allele of the major histocompatibility complex class I chain-related
      gene A is associated with psoriasis vulgaris in Chinese.
AB  - BACKGROUND: Recent studies have demonstrated an association of a polymorphic
      (GCT)n triplet repeat in the transmembrane (TM) region of the major
      histocompatibility complex (MHC) class I chain-related gene A (MICA), one of the
      MHC class I chain-related (MIC) family members, with some autoimmune diseases,
      including Behcet's disease, acute anterior uveitis, Takayasu's arteritis and
      others. OBJECTIVES: The aim of this study was to examine whether the MICA gene is
      associated with psoriasis vulgaris (PS) in Chinese. PATIENTS AND METHODS: The
      (GCT)n polymorphism of the MICA gene was investigated in 200 healthy Chinese of
      Han origin and 300 patients with PS by polymerase chain reaction amplification
      and denaturing polyacrylamide gel electrophoresis. RESULTS: Five alleles, namely
      A4, A5, A6, A9 and A5.1 were found in both groups. Comparison of the data from
      both groups revealed that the A5.1 allele was present at a significantly higher
      frequency in the patient group (41.5%) than in the control group (23.0%) (Pc <
      0.0001, Pc means the probability of a comparison with the control group). The
      frequency of A5.1-positive cases was also significantly increased in the patient
      group (68.0%) as compared with the controls (38.0%) (Pc < 0.0001). Furthermore,
      the carrier frequency of A5.1-positive was significantly increased in psoriatic
      patients with a positive family history and with early onset as compared with
      sporadic cases (Pc = 0.0005) and with late onset PS (Pc = 0.002). CONCLUSIONS:
      These results suggest that the MICA gene may be associated with the development
      of PS in Chinese.

PMID- 10951141
TI  - Human keratinocytes constitutively produce but do not process interleukin-18.
AB  - BACKGROUND: Interleukin (IL)-18 is a potent immunomodulatory cytokine which
      promotes T-helper (Th) 1 and cytotoxic responses. IL-18 signals through a two
      chain receptor (IL-18R and accessory protein-like subunit, AcPL), and an
      inhibitory molecule, IL-18 binding protein (IL-18BP), has recently been
      characterized. OBJECTIVES: The aim of the present study was to define the
      production of IL-18 and its receptor by human keratinocytes. METHODS: The
      presence of IL-18 was determined using polymerase chain reaction in human
      keratinocyte cultures with or without treatment with potential inducers. RESULTS:
      The IL-18 gene was constitutively transcribed by primary human keratinocytes and
      cell lines and was not significantly altered following exposure to IL-1 beta,
      tumour necrosis factor-alpha, interferon (IFN)-gamma, phorbol myristate acetate
      or nickel sulphate. IL-18 protein was constitutively present at high levels in
      keratinocyte lysates and was detectable in supernatants exclusively in the
      unprocessed, 24-kDa form. Cytokine exposure failed to induce any change in
      protein levels or processing. Primary keratinocytes produced IL-18R and AcPL
      constitutively at the mRNA level, in addition to low levels of IL-18BP, which was
      transcriptionally inducible following treatment with IFN-gamma. CONCLUSIONS:
      These findings demonstrate that IL-18 is constitutively synthesized by human
      keratinocytes and is released in an unprocessed form in vitro. Release of IL-18
      by human keratinocytes may permit them to regulate IFN-gamma production during
      cutaneous inflammatory responses and suggests that IL-18 may represent an
      attractive target for immunomodulatory intervention in Th1-mediated inflammatory
      diseases such as psoriasis.

PMID- 10951142
TI  - The distribution of pemphigus vulgaris-IgG subclasses and their reactivity with
      desmoglein 3 and 1 in pemphigus patients and their first-degree relatives.
AB  - BACKGROUND: Pemphigus vulgaris (PV) autoantibodies (PV-IgG) have been found in 40
      70% of sera of first-degree relatives of pemphigus patients. OBJECTIVES: To
      determine the possible role of PV-IgG subclasses in the pathogenesis of the
      disease. PATIENTS AND METHODS: Study groups comprised 25 PV patients, 55
      unaffected family members and 56 sera of healthy individuals. Indirect
      immunofluorescence (IIF) staining and Western immunoblotting (WB) techniques were
      used to determine total PV-IgG and PV-IgG subclasses and their reactivity to
      desmoglein (Dsg) 1 and 3. RESULTS: By IIF staining, circulating PV-IgG were found
      in 64% of the patients, in 15% of the relatives and in none of the controls (P <
      or = 0.001); by WB the results were 91%, 49% and 12%, respectively (P < or =
      0.001). The distribution of PV-IgG subclasses 1-3 was similar among patients and
      their relatives. PV-IgG4 was found in 62% of the patients but in only one
      relative and was absent in the controls (P < or = 0.001). PV-IgG1, 2 and 4 were
      found to react mainly with Dsg3 and PV-IgG3 mainly with Dsg1 and 3. CONCLUSIONS:
      These results support the concept of a genetic predisposition in pemphigus. The
      non-complement-fixing PV-IgG4 and at least one complement-fixing PV-IgG subclass
      appear to be involved in the pathogenesis of the disease. The absence of PV-IgG4
      among relatives who were PV-IgG carriers seems to be linked to the fact that they
      do not develop pemphigus. The exact nature of this linkage is still unclear.

PMID- 10951143
TI  - A study of desmoglein 1 autoantibodies in pemphigus vulgaris: racial differences
      in frequency and the association with a more severe phenotype.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is characterized by pathogenic autoantibodies
      to desmoglein (Dsg) 3, but additional antibodies to Dsg1, the pemphigus foliaceus
      antigen, are detectable in some cases. OBJECTIVES: To investigate the clinical
      significance of the presence of both Dsg 1 and 3 antibodies. METHODS: In 79
      subjects with PV, enzyme-linked immunosorbent assays were used to detect IgG
      autoantibodies reactive with the ectodomain of Dsg1 and Dsg3. RESULTS: There was
      a clear association between the clinical phenotype and the Dsg antibody profile.
      All subjects had Dsg3 autoantibodies and 61% had coexisting Dsg1 antibodies
      (Dsg3+/Dsg1+). PV limited entirely to the mucosal surfaces was seen only in
      Dsg3+/Dsg1- patients, while additional Dsg1 antibodies (Dsg3+/Dsg1+) predicted
      cutaneous in addition to mucosal involvement. Although minor cutaneous
      involvement was observed in most Dsg3+/Dsg1- patients, severe cutaneous
      involvement was seen only in Dsg3+/Dsg1+ patients. Dsg1 antibodies were
      detectable early in the course of disease and their appearance did not relate to
      the use of systemic therapy. The proportion of Dsg1+ patients was higher in those
      of Indian origin compared with white northern Europeans (P < 0.05). CONCLUSIONS:
      These data suggest that the presence of Dsg1 antibodies is predictive of a
      potentially more severe disease and that genetic factors may determine the Dsg
      antibody profile.

PMID- 10951144
TI  - IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with
      bullous and cicatricial pemphigoid and linear IgA bullous dermatosis.
AB  - BACKGROUND: Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and
      cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin
      diseases characterized by autoantibodies against components of the epidermal
      basement membrane. Like most patients with BP, a significant subgroup of patients
      with CP has circulating IgG specific for BP180, a transmembraneous protein of
      hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies
      reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to
      the extracellular portion of BP180. OBJECTIVES: We aimed to determine whether, in
      these diseases, autoantibody reactivity to BP180 is restricted to distinct
      immunoglobulin subtypes. METHODS: Utilizing a baculovirus-encoded form of the
      ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n =
      10) and normal human control sera (n = 10) were analysed by immunoblot for IgG,
      IgA and IgE reactivity against BP180. RESULTS: All of 10 BP sera displayed IgG,
      IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively,
      contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera
      contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10
      IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to
      BP180. CONCLUSIONS: The presence of IgG and IgA autoantibody responses to BP180
      in patients with three clinically distinct autoimmune bullous diseases indicates
      that an autoimmune response to the same distinct adhesion protein may lead to
      different clinical manifestations. It is therefore conceivable that variable
      epitopes of BP180 are targeted by the different autoantibody isotypes, resulting
      in the distinct clinical pictures.

PMID- 10951145
TI  - A prospective study of the impact of laser treatment on vascular lesions.
AB  - BACKGROUND: Vascular lesions, especially on exposed sites, can be unsightly and
      may cause significant psychological distress. Lasers are effective in treating
      such lesions, but relatively few studies have been performed looking at
      psychological scoring before and after laser therapy. OBJECTIVES: To assess the
      change in psychological distress in patients with vascular lesions following
      laser treatment. PATIENTS AND METHODS: A prospective study was performed with
      patients recruited over a 3-month period. Psychological distress was measured
      using subjective scores on a standard questionnaire before treatment and at a 6
      month follow-up. Each patient was treated every 4-8 weeks with an appropriate
      laser by the same dermatologist until discharge. Forty-two patients were
      recruited with one of four diagnoses: telangiectasia, port wine stain (PWS),
      vascular spider or cherry angioma, which occurred mainly on facial or exposed
      sites. RESULTS: Following laser treatment, there was a significant decrease in
      subjective scores of patients with telangiectasia and vascular spiders. Patients
      with PWS showed objective improvement but this was not reflected in their
      subjective scores. Psychological distress had reduced significantly in patients
      with less severe vascular lesions. CONCLUSIONS: Laser treatment of minor vascular
      lesions leads to objective improvement, which is paralleled by psychological
      benefit, but objective benefit in PWS may not be perceived as beneficial by
      patients.

PMID- 10951146
TI  - Can the response of port-wine stains to laser treatment be reliably assessed
      using subjective methods?
AB  - Assessing the results of laser treatment of port-wine stains (PWS) is very
      subjective. Most publications use scoring systems that physically describe the
      change in PWS after treatment. For results derived from such an analysis to be
      meaningful, the observers must be able to produce results that not only have a
      small interobserver variability but are also reproducible. Previous studies have
      addressed the former but not the latter. The present study was undertaken to
      investigate this area of concern. Six professionals, experienced in laser work,
      blindly assessed the response to laser treatment of 20 PWS, on two occasions, 1
      month apart. Twenty pairs of comparable clinical photographs (one pretreatment
      and one post-treatment) were assessed using three different scoring systems
      commonly used in previous publications. Intrarater concordance between the two
      sessions was then assessed. Our results demonstrated that the judges could only
      consistently score results at the extremes of outcome. There was little agreement
      in the assessment of results lying between these. The judges were, however,
      consistently able to place a similar proportion of patients in each outcome
      category. We conclude that, as yet, there is no satisfactory method of monitoring
      the progress of an individual's PWS following laser treatment. However, the
      scoring systems examined would seem to be reasonable for presenting the data from
      patient series.

PMID- 10951147
TI  - Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria.
AB  - BACKGROUND: Histamine-releasing activity (HRA) is detectable in up to 50% of
      patients with chronic ordinary urticaria. OBJECTIVES: To determine the effect of
      cyclosporin on clinical features and HRA in patients with chronic urticaria.
      METHODS: Thirty patients with severe unremitting disease, responding poorly to
      antihistamines and showing a positive autologous serum skin test (ASST) as a
      marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n =
      20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label
      cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical
      relapse; all took cetirizine 20 mg daily throughout the study. The primary
      measure of efficacy was a daily urticaria activity score (UAS) of weal numbers
      and itch (maximum score 42 per week). A positive response was defined as a
      reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The
      effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine
      release assays and ASSTs before and after treatment. RESULTS: Twenty-nine
      patients (19 active, 10 controls) completed the randomized trial medication.
      Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P <
      0.05). Three others on active drug met the criterion for response at 2 weeks but
      not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95%
      confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for
      placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10
      to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of
      the eight randomized active drug responders relapsed within 6 weeks. Of the 19
      responders to randomized and open-label cyclosporin, five (26%) had not relapsed
      by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to
      5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST
      response to post-treatment serum was also reduced (P < 0.05). CONCLUSIONS: This
      study shows that cyclosporin is effective for chronic urticaria and provides
      further evidence for a role of histamine-releasing autoantibodies in the
      pathogenesis of this chronic 'idiopathic' disease.

PMID- 10951148
TI  - Increased circulating skin-homing cutaneous lymphocyte-associated antigen (CLA)+
      type 2 cytokine-producing cells, and decreased CLA+ type 1 cytokine-producing
      cells in atopic dermatitis.
AB  - BACKGROUND: Skin-homing T cells are characterized by expression of cutaneous
      lymphocyte-associated antigen (CLA). Few data are available on the frequency of
      circulating CLA+ cytokine-producing T cells in atopic dermatitis (AD) patients.
      OBJECTIVES: We aimed to investigate cytokine synthesis capability vs. CLA
      expression in phorbol myristate acetate and ionomycin-stimulated, secretion
      inhibited peripheral blood T cells of AD patients compared with healthy subjects
      and psoriatic patients. METHODS: Multiparameter flow cytometry was used. RESULTS:
      The expression of CLA among CD4+ T cells was significantly elevated in AD
      patients compared with healthy subjects and psoriatic patients, whereas there was
      no significant difference between each group in CLA expression among CD8+ T
      cells. The frequency of interleukin (IL)-4- and IL-13-producing cells in AD
      patients was significantly higher than in healthy subjects (in both CD4+ and CD8+
      T-cell subsets) and psoriatic patients (in CD4+ T cells). In contrast, the
      frequency of interferon (IFN)-gamma-producing cells was significantly reduced in
      AD patients, among both CD4+ and CD8+ T cells, compared with healthy subjects and
      psoriatic patients. Moreover, in AD patients, the frequency of IL-4- and IL-13
      producing cells was remarkably increased among the CLA+ subset (in both CD4+ and
      CD8+ T cells), whereas the frequency of IFN-gamma-producing cells was decreased
      in the CLA+ subset (in CD4+, but not in CD8+ T cells). CONCLUSIONS: These results
      provide evidence for the expansion of skin-homing type 2 cytokine-secreting T
      cells, associated with a reduction in skin-homing type 1 cytokine-producing T
      cells, in peripheral blood of AD patients.

PMID- 10951149
TI  - Effect of house dust mite avoidance measures in children with atopic dermatitis.
AB  - BACKGROUND: House dust mite allergens are associated with atopic dermatitis (AD).
      OBJECTIVES: The aim of our study was to verify if house dust mite allergen
      avoidance measures can improve the clinical manifestations of AD in children.
      METHODS: Forty-one children (mean age 3.9 years) affected by AD associated with
      high total and/or specific IgE serum levels ('extrinsic' AD) were recruited.
      Clinical evaluation was performed utilizing the Severity Scoring of AD (SCORAD)
      index; dust was sampled from the children's beds and tested using an enzyme
      linked immunosorbent assay. The study was planned in two parts. In the first
      part, a placebo-controlled trial of 2 months duration, mite allergen avoidance
      measures (encasing mattresses and pillows; a weekly hot wash of bedding; frequent
      vacuum cleaning of living room and bedroom; soft toys and carpets regularly
      cleaned or removed; no pets allowed) were recommended to group A patients, but
      not to group B. In the second part of the study, environmental avoidance measures
      were recommended to initial control group B patients also. One year after the
      start of the study the amounts of mite allergen in the home and clinical score of
      AD were measured in both groups. RESULTS: At the end of the first part of the
      study, significant decreases in major allergens of Dermatophagoides pteronyssinus
      (Der p1) and D. farinae (Der f1) load (from 393 to 94 ng m-2) and concentration
      (from 1.84 to 0.73 microg g-1 of dust) in children's beds were observed in
      treatment group A. At the same time, in this group the mean SCORAD index improved
      significantly (from 33 to 26; P = 0.022). After 12 months, when all patients had
      used allergen avoidance measures, Der p1 + Der f1 load, concentration and
      clinical score had improved, reaching similar values in both groups. CONCLUSIONS:
      Simple mite allergen avoidance measures should be recommended to families with
      children affected by extrinsic AD in order to control the clinical manifestations
      and prevent mite sensitization.

PMID- 10951150
TI  - Treatment of atopic eczema with oral mycophenolate mofetil.
AB  - BACKGROUND: Activated T and B lymphocytes are the predominant inflammatory cells
      in atopic eczema (AE) lesions. Mycophenolic acid, the active form of
      mycophenolate mofetil (MMF), blocks the proliferative responses of T and B
      lymphocytes. OBJECTIVES: In this pilot study, we examined the efficacy of MMF
      (CellCept(R), Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE. METHODS:
      Ten patients with severe AE (severity index > 50) according to the Severity
      Scoring of Atopic Dermatitis (SCORAD) index were treated with oral MMF at an
      initial dose of 1 g daily during the first week and 2 g daily for a further 11
      weeks. Laboratory examination including full blood count, lymphocyte subset
      analysis, serum immunoglobulins (IgE, IgG, IgM, IgA), total bilirubin, alkaline
      phosphatase, aminotransferases, lactate dehydrogenase and creatinine was
      performed every 2 weeks. Additionally, interleukin (IL)-10 and interferon (IFN)
      gamma in serum were measured. RESULTS: None of the 10 patients who received MMF
      discontinued the trial because of lack of efficacy or adverse events. Compared
      with the baseline, the median scores for disease severity (SCORAD index) improved
      by 68% during treatment with MMF. The median serum IgE level decreased
      significantly, from 10,300 kU L-1 before treatment to 7830 kU L-1 after 12 weeks.
      MMF induced a significant increase in the T-helper (Th)-1-related cytokine IFN
      gamma and a significant decrease in IL-10, mainly produced by Th2 cells.
      CONCLUSIONS: The present study demonstrates that oral MMF at a dose of 2 g daily
      is an effective, safe and well-tolerated immunosuppressive therapy for severe AE
      in adults.

PMID- 10951151
TI  - Increased serum levels of soluble vascular cell adhesion molecule-1 and soluble E
      selectin in patients with polymyositis/dermatomyositis.
AB  - BACKGROUND: Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM
      1) and soluble E-selectin (sE-selectin) have previously been reported in patients
      with various inflammatory diseases, but not in patients with
      polymyositis/dermatomyositis (PM/DM). OBJECTIVES: To determine serum levels and
      significance of sVCAM-1 and sE-selectin in patients with PM/DM. PATIENTS AND
      METHODS: Serum samples from 36 PM/DM patients, 30 patients with systemic
      sclerosis and 25 healthy control subjects were examined using specific enzyme
      linked immunosorbent assay systems. RESULTS: The serum levels of sVCAM-1 in the
      PM/DM patients were significantly higher than those in the healthy controls. The
      elevated serum sVCAM-1 levels were correlated with the values of elevated
      erythrocyte sedimentation rate and elevated serum hyaluronate levels in the PM/DM
      patients. The serum sE-selectin levels in the PM/DM patients were also
      significantly higher than those in the healthy controls. The elevated serum sE
      selectin levels were correlated with the incidence of elevated creatine kinase
      activities. The concentrations of serum sE-selectin were correlated with the
      serum tissue inhibitor of metalloproteinase-1 concentrations in the PM/DM
      patients (r = 0.53). CONCLUSIONS: These results suggest that serum sVCAM-1 and sE
      selectin levels might be useful for detecting disease activity in patients with
      PM/DM.

PMID- 10951152
TI  - The role of androgens in determining acne severity in adult women.
AB  - BACKGROUND: Although many arguments have been put forth supporting the role of
      androgens in the aetiology of acne, their part in determining the severity of the
      disease is not well established. OBJECTIVES: The aim of our study was to evaluate
      the relationship between acne severity and the clinical and laboratory markers of
      androgenicity in a large group of patients. METHODS: Ninety women over 17 years
      of age with acne were enrolled into the study. The levels of testosterone,
      androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate and sex
      hormone binding globulin (SHBG) were measured. Menstrual cycle regularity,
      hirsutism score, acne severity and ultrasound evaluation of polycystic ovaries
      were recorded. One-way analysis of variance, chi(2)-test and correlation analysis
      were used for data processing. RESULTS: Hirsutism was documented in 19 (21%)
      subjects, elevated levels of at least one androgen in 73 (81%) subjects, an
      irregular cycle was reported by 43 (48%) women, and polycystic ovaries were found
      in 45 (50%) women. The patients were divided into three groups according to acne
      severity. Acne was graded using the Leeds technique as minor in 43 (48%) cases,
      mild in 27 (30%) and moderate in 20 (22%). We did not demonstrate a positive
      correlation between the grade of acne severity and any of the clinical or
      laboratory markers of androgenicity assessed. On the contrary, women with a
      higher grade of acne severity showed lower values of the index of free
      testosterone, a lower hirsutism score and higher SHBG levels. CONCLUSIONS: Our
      study suggests that the severity of acne manifestation in adult women is not
      determined by androgen production.

PMID- 10951153
TI  - Change of treatment from cyclosporin to mycophenolate mofetil in severe
      psoriasis.
AB  - Eight patients whose severe psoriasis was treated with long-term cyclosporin
      (range 2-11 years; mean 7.6 years) were changed to mycophenolate mofetil (MMF),
      because of nephrotoxicity in seven and hypertension and lack of efficacy in one.
      In five patients psoriasis control significantly deteriorated and in three
      patients disease control deteriorated slightly in periods ranging from 2 to 32
      weeks. Renal function improved in all six patients with cyclosporin-induced
      nephrotoxicity treated with MMF for more than 2 weeks. From this data it would
      appear that MMF is not as effective as cyclosporin in controlling severe
      psoriasis. However, MMF did offer reasonable disease control in three of eight
      patients and allowed renal function to improve, and so may have a place in the
      treatment of some patients unable to take cyclosporin because of renal toxicity.

PMID- 10951154
TI  - Aggressive subcutaneous panniculitis-like T-cell lymphoma: complete remission
      with fludarabine, mitoxantrone and dexamethasone.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL) is a rare cutaneous T
      cell lymphoma. The optimal treatment of this disease is undefined. A 36-year-old
      woman presented with swinging pyrexia, weight loss and disseminated SCPTCL
      involving her limbs and trunk. Typical histological features of panniculitic
      infiltration with rimming of fat cells and sparing of the dermis and epidermis
      were seen. Immunophenotyping confirmed a CD8+ cytotoxic T-cell phenotype. The
      patient was successfully treated with a combination of fludarabine, mitoxantrone
      and dexamethasone (FND), and has remained in remission 15 months after cessation
      of treatment. FND may be an effective regimen for aggressive SCPTCL.

PMID- 10951155
TI  - Cutaneous pseudolymphoma, lymphomatoid contact dermatitis type, as an unusual
      cause of symmetrical upper eyelid nodules.
AB  - We describe a 74-year-old woman who rapidly developed bilateral voluminous
      nodules on the upper eyelids, following 4 months' treatment for chalazion.
      Histological and immunohistochemical findings were suggestive of cutaneous
      pseudolymphoma (CPL), and extensive screening for malignant lymphoma (ML)
      remained negative. Cutaneous pseudolymphomas are inflammatory diseases that can
      simulate ML either clinically, histopathologically, or both. They are a rare
      cause of nodules of the upper eyelids, usually characterized by a benign
      evolution, that can be secondary to ultraviolet sensitivity, adverse reactions to
      systemic medications and contact sensitization, among others. In our case,
      epicutaneous patch tests were strongly positive for a series of allergens
      contained in the ophthalmological preparations used; therefore, they were
      suggestive that the patient had CPL, lymphomatoid contact dermatitis type. In
      addition, the patient had been treated previously with several drugs, known to
      cause CPL and immune dysregulation. Complete regression of the lesions required
      treatment with systemic steroids and chlorambucil. No relapse occurred within a 5
      year follow-up period.

PMID- 10951156
TI  - Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations
      and response to dapsone.
AB  - Erythema elevatum diutinum (EED) is a type of leucocytoclastic vasculitis of
      unknown aetiology. We report a patient with unusually widespread and disabling
      EED that had been unresponsive to corticosteroids and antibiotics, but resolved
      on dapsone. Biopsies of fresh lesions showed typical features of leucocytoclastic
      vasculitis, with prominent neutrophil infiltration, marked expression of the
      beta(2)-integrins CR3 and LFA-1, and increased mast cell numbers. Older lesions
      exhibited granulation tissue and fibrosis, macrophages were more dominant,
      beta(2)-integrins were expressed less markedly, and mast cell numbers were lower.
      In vitro chemotaxis of the patient's peripheral blood neutrophils prior to
      treatment showed increased random migration and directed migration towards
      interleukin-8 (by 424%), but a profoundly decreased responsiveness towards the
      bacterial peptide analogue N-formyl-methionyl-leucyl-phenylalanine (fMLP) (by
      98%). These values returned to normal after dapsone treatment and clinical
      improvement 5 months later. These findings support the concept that in EED,
      activation via cytokines such as interleukin-8 allows a selective recruitment of
      leucocytes to tissue sites, while immune complexes and bacterial peptides sustain
      the persistent local inflammatory infiltrate and the leucocytoclastic vasculitis.

PMID- 10951157
TI  - Eosinophilic spongiosis in association with bullous pemphigoid and chronic
      lymphocytic leukaemia.
AB  - We report the onset of an unusual blistering eruption following a diagnosis of B
      cell chronic lymphocytic leukaemia (CLL). The histology consistently showed
      eosinophilic spongiosis, but the diagnosis of bullous pemphigoid was only
      confirmed after 13 years by repeated immunofluorescence studies. The occurrence
      of subepidermal blistering diseases in association with B-cell
      lymphoproliferative disorders is rare; a recent study showed that the majority of
      these cases are epidermolysis bullosa acquisita, confirmed by immunological
      studies. Only two cases of immunofluorescence-proven bullous pemphigoid in
      association with CLL have been previously reported.

PMID- 10951158
TI  - Wells' syndrome associated with recurrent giardiasis.
AB  - Wells' syndrome (WS) is a rare, recurrent, inflammatory dermatosis of uncertain
      pathogenesis, although a hypersensitivity response to different stimuli has been
      postulated. Several cases in association with parasitic infections have been
      described. We present a patient with WS associated with recurrent giardiasis. The
      course of the dermatosis was strictly related to the course of the parasitic
      infection. Both diseases disappeared with antiparasitic treatment. To our
      knowledge, this association is here reported for the first time.

PMID- 10951159
TI  - Angio-oedema in a neonate with IgG antibodies to parvovirus B19 following
      intrauterine parvovirus B19 infection.
AB  - We report a neonate with angio-oedema following fetal hydrops caused by maternal
      parvovirus B19 infection. Levels of complement components, including total
      haemolytic complement activity and C1 inhibitor concentration, were within normal
      ranges in cord blood. Neonatal angio-oedema might be included in the clinical
      spectrum of parvovirus B19 infection in pregnancy.

PMID- 10951160
TI  - Early malignant melanoma manifested as longitudinal melanonychia: subungual
      melanoma may arise from suprabasal melanocytes.
AB  - A 51-year-old woman developed longitudinal melanonychia of 3 months' duration on
      the right index fingernail. A biopsy specimen revealed that atypical melanocytes
      were distributed in the lower third of the matrix epithelium but were few in
      number at the basal layer. The involved nail matrix was resected because of
      continual growth of the lesion after the biopsy. It has been proven in normal
      nail matrices that melanocytes are distributed not only in the basal layer but
      also in the lower half of the epithelium. It is therefore understandable that
      malignant melanoma of the nail matrix can arise from melanocytes situated in the
      squamous epithelium above the basal layer. The present case is a good example in
      which malignant melanoma of the nail matrix may arise from the intraepithelial
      region where melanocytes normally reside.

PMID- 10951161
TI  - Eruptive pseudoangiomatosis.
AB  - Eruptive pseudoangiomatosis (EPA) is a rare, benign, spontaneously regressing
      childhood exanthem. The term was recently coined by Prose et al.1 to describe a
      dermatosis characterized by the sudden onset of a few to several bright red
      angioma-like papules with a different histopathology from the true angiomas. We
      describe three patients with the typical lesions of EPA but with some peculiar
      features not previously described. We discuss the suspected viral aetiology of
      EPA, and hypothesize a multifactorial aetiopathogenesis.

PMID- 10951162
TI  - Mycosis fungoides and chronic lymphocytic leukaemia--composite T-cell and B-cell
      lymphomas presenting in the skin.
AB  - Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very
      uncommon. We report here the unique circumstance of a patient with mycosis
      fungoides (primary cutaneous T-cell lymphoma) who later developed chronic
      lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the
      skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence
      of both lymphoproliferative disorders was confirmed with immunophenotyping and
      the finding of both immunoglobulin gene rearrangements and T-cell receptor gene
      rearrangements in the ear and the same T-cell receptor gene rearrangement in a
      plaque lesion of mycosis fungoides on the arm.

PMID- 10951163
TI  - Cutaneous thrombotic and necrotizing microangiopathy revealing a large granular
      lymphocytic leukaemia.

PMID- 10951164
TI  - Successful treatment of chronic leucocytoclastic vasculitis and persistent
      ulceration with intravenous immunoglobulin.

PMID- 10951165
TI  - Sweet's syndrome presenting with lesions resembling eruptive xanthoma.

PMID- 10951166
TI  - Scleredema of Buschke associated with Waldenstrom's macroglobulinaemia.

PMID- 10951167
TI  - Lichen myxedematosus in a patient with hepatocellular carcinoma.

PMID- 10951168
TI  - Cyclophosphamide therapy is effective for bronchiolitis obliterans occurring as a
      late manifestation of lupus erythematosus.

PMID- 10951169
TI  - Severe exacerbation of pemphigus vulgaris in pregnancy: successful treatment with
      plasma exchange.

PMID- 10951170
TI  - Pemphigus foliaceus associated with silicosis.

PMID- 10951171
TI  - Recurrent mucinous carcinoma of the skin invading to the frontal skull base.

PMID- 10951172
TI  - Verrucous 'cuniculatum' carcinoma of the sacral region.

PMID- 10951173
TI  - Neuroendocrine carcinoma of the skin with a lymphoepithelioma-like histological
      pattern.

PMID- 10951174
TI  - Digital arteriovenous malformation.

PMID- 10951175
TI  - Subungual abscess: a new ungual side-effect related to docetaxel therapy.

PMID- 10951176
TI  - PUVA-bath photochemotherapy for congenital palmoplantar keratoderma in an 11-year
      old girl.

PMID- 10951177
TI  - Acne keloidalis in caucasian patients on cyclosporin following organ
      transplantation.

PMID- 10951178
TI  - Magnetic Resonance Imaging in the investigation of penile lymphangioma
      circumscriptum.

PMID- 10951179
TI  - Cutaneous entrapment of the shed cilium.

PMID- 10951180
TI  - A palmar epidermoid cyst, showing histological features suggestive of eccrine
      duct origin, developing after a bee-sting.

PMID- 10951181
TI  - FEBS in the new millennium

PMID- 10951182
TI  - Calcium signalling, coming of age.

PMID- 10951183
TI  - The renaissance of mitochondrial calcium transport.
AB  - Although the capacity of mitochondria for accumulating Ca2+ down the electrical
      gradient generated by the respiratory chain has been known for over three
      decades, the physiological significance of this phenomenon has been re-evaluated
      only recently. Indeed, it was long believed that the low affinity of the
      mitochondrial Ca2+ transporters would allow significant uptake only in conditions
      of cellular Ca2+ overload. Conversely, the direct measurement of [Ca2+] in the
      mitochondrial matrix revealed major [Ca2+] increases upon agonist stimulation. In
      this review, we will summarize: (a) the mechanisms that allow this large
      response, reconciling the biochemical properties of the transporters and the
      large amplitude of the mitochondrial [Ca2+] rises, and (b) the biological role of
      mitochondrial Ca2+ signalling, that encompasses the regulation of mitochondrial
      function and the modulation of the spatio-temporal pattern of cytosolic [Ca2+]
      increases.

PMID- 10951184
TI  - Calcium transport across the sarcoplasmic reticulum: structure and function of
      Ca2+-ATPase and the ryanodine receptor.
AB  - Contraction of striated muscle results from a rise in cytoplasmic calcium
      concentration in a process termed excitation/contraction coupling. Most of this
      calcium moves back and forth across the sarcoplasmic-reticulum membrane in cycles
      of contraction and relaxation. The channel responsible for release from the
      sarcoplasmic reticulum is the ryanodine receptor, whereas Ca2+-ATPase effects
      reuptake in an ATP-dependent manner. The structures of these two molecules have
      been studied by cryoelectron microscopy, with helical crystals in the case of
      Ca2+-ATPase and as isolated tetramers in the case of ryanodine receptor.
      Structures of Ca2+-ATPase at 8-A resolution reveal the packing of transmembrane
      helices and have allowed fitting of a putative ATP-binding domain among the
      cytoplasmic densities. Comparison of ATPases in different conformations gives
      hints about the conformational changes that accompany the reaction cycle.
      Structures of ryanodine receptor at 30-A resolution reveal a multitude of
      isolated domains in the cytoplasmic portion, as well as a distinct transmembrane
      assembly. Binding sites for various protein ligands have been determined and
      conformational changes induced by ATP, calcium and ryanodine have been
      characterized. Both molecules appear to use large conformational changes to
      couple interactions in their cytoplasmic domains with calcium transport through
      their membrane domains, and future studies at higher resolution will focus on the
      mechanisms for this coupling.

PMID- 10951185
TI  - Transcription-dependent neuronal plasticity: The nuclear calcium hypothesis.
AB  - In neurons, calcium ions control gene transcription induced by synaptic activity.
      The states and histories of neuronal activity are represented by a calcium code
      that comprises the site of calcium entry, and the amplitude, duration and spatial
      properties of signal-evoked calcium transients. The calcium code is used to
      transform specific firing patterns into qualitatively and quantitatively distinct
      transcriptional responses. The following hypothesis is proposed: electrical
      activity causes long-lasting, transcription-dependent changes in neuronal
      functions when synaptically evoked calcium transients associated with the
      stimulation propagate to the nucleus; gene transcription activated by dendritic
      calcium signals only is insufficient to consolidate functional alterations long
      term. Similar to enduring increases in synaptic efficacy, nuclear calcium
      transients are induced by high-frequency firing patterns or by weak synaptic
      inputs coinciding with backpropagating dendritic action potentials. Nuclear
      calcium stimulates CREB-mediated transcription and, through inducing the activity
      of the transcriptional coactivator CREB-binding protein (CBP), may modulate the
      expression of numerous genes including neurotransmitter receptors and scaffolding
      proteins. Increases in the transcription rate of target genes are predicted to be
      transient and in many cases small, however, they collectively contribute to the
      maintenance of changes in synaptic efficacy. Nuclear calcium may be the common
      regulator of diverse transcription-dependent forms of neuronal plasticity.

PMID- 10951186
TI  - Gene knockout studies of Ca2+-transporting ATPases.
AB  - The biochemical functions of intracellular and plasma membrane Ca2+-transporting
      ATPases in the control of cytosolic and organellar Ca2+ levels are well
      established, but the physiological roles of specific isoforms are less well
      understood. There appear to be three different types of Ca2+ pumps in mammalian
      tissues: the sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), which sequester
      Ca2+ within the endoplasmic or sarcoplasmic reticulum, the plasma membrane Ca2+
      ATPases (PMCAs), which extrude Ca2+ from the cell, and the putative secretory
      pathway Ca2+-ATPase (SPCA), the function of which is poorly understood. This
      review describes the results of recent analyses of mouse models with null
      mutations in the genes encoding SERCA and PMCA isoforms and genetic studies of
      SERCA and SPCA dysfunction in both humans and model organisms. These studies are
      yielding important insights regarding the physiological functions of individual
      Ca2+-transporting ATPases in vivo.

PMID- 10951187
TI  - Ca2+ signalling and muscle disease.
AB  - Transient elevations of intracellular Ca2+ play a signalling role in such complex
      cellular functions as contraction, secretion, fertilization, proliferation,
      metabolism, heartbeat and memory. However, prolonged elevation of Ca2+ above
      about 10 microM is deleterious to a cell and can activate apoptosis. In muscle,
      there is a narrow window of Ca2+ dysregulation in which abnormalities in Ca2+
      regulatory proteins can lead to disease, rather than apoptosis. Key proteins in
      the regulation of muscle Ca2+ are the voltage-dependent, dihydropyridine
      sensitive, L-type Ca2+ channels located in the transverse tubule and Ca2+ release
      channels in the junctional terminal cisternae of the sarcoplasmic reticulum.
      Abnormalities in these proteins play a key role in malignant hyperthermia (MH), a
      toxic response to anesthetics, and in central core disease (CCD), a muscle
      myopathy. Sarco(endo)plasmic reticulum Ca2+ ATPases (SERCAs) return sarcoplasmic
      Ca2+ to the lumen of the sarcoplasmic reticulum. Loss of SERCA1a Ca2+ pump
      function is one cause of exercise-induced impairment of the relaxation of
      skeletal muscle, in Brody disease. Phospholamban expressed in cardiac muscle and
      sarcolipin expressed in skeletal muscle regulate SERCA activity. Studies with
      knockout and transgenic mice show that gain of inhibitory function of
      phospholamban alters cardiac contractility and could be a causal feature in some
      cardiomyopathies. Calsequestrin, calreticulin, and a series of other acidic,
      lumenal, Ca2+ binding proteins provide a buffer for Ca2+ stored in the
      sarcoplasmic reticulum. Overexpression of cardiac calsequestrin leads to
      cardiomyopathy and ablation of calreticulin alters cardiac development.

PMID- 10951188
TI  - Symmetry and structure in P-glycoprotein and ABC transporters what goes around
      comes around.
AB  - The ABC superfamily of membrane transporters is one of the largest classes of
      proteins across all species and one of the most intensely researched. ABC
      proteins are involved in the trafficking of a diverse variety of biological
      molecules across cell membranes, with some members implicated in medical
      syndromes such as cystic fibrosis and multidrug resistance to anti-cancer drugs.
      In the absence of X-ray crystallographic data, structural information has come
      from spectroscopy, electron microscopy, secondary structure prediction algorithms
      and residue substitution, epitope labelling and cysteine cross-linking studies.
      These have generally supported a model for the topology of the transmembrane
      domains of ABC transporters in which a single aqueous pore is formed by a
      toroidal ring of 12 alpha helices, deployed in two arcs of six helices each.
      Although this so-called 6 + 6 helix model can be arranged in either mirror or
      rotational symmetry configurations, experimental data supports the former. In
      this review, we put forward arguments against both configurations of this 6 + 6
      helix model, based on what is known generally about symmetry relationships in
      proteins. We relate these arguments to P-glycoprotein, in particular, and discuss
      alternative models for the structure of ABC transporters in the light of the most
      recent research.

PMID- 10951190
TI  - Can yeast glycolysis be understood in terms of in vitro kinetics of the
      constituent enzymes? Testing biochemistry.
AB  - This paper examines whether the in vivo behavior of yeast glycolysis can be
      understood in terms of the in vitro kinetic properties of the constituent
      enzymes. In nongrowing, anaerobic, compressed Saccharomyces cerevisiae the values
      of the kinetic parameters of most glycolytic enzymes were determined. For the
      other enzymes appropriate literature values were collected. By inserting these
      values into a kinetic model for glycolysis, fluxes and metabolites were
      calculated. Under the same conditions fluxes and metabolite levels were measured.
      In our first model, branch reactions were ignored. This model failed to reach the
      stable steady state that was observed in the experimental flux measurements.
      Introduction of branches towards trehalose, glycogen, glycerol and succinate did
      allow such a steady state. The predictions of this branched model were compared
      with the empirical behavior. Half of the enzymes matched their predicted flux in
      vivo within a factor of 2. For the other enzymes it was calculated what deviation
      between in vivo and in vitro kinetic characteristics could explain the
      discrepancy between in vitro rate and in vivo flux.

PMID- 10951189
TI  - Nucleotide-binding domain 1 of cystic fibrosis transmembrane conductance
      regulator production of a suitable protein for structural studies.
AB  - Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis
      transmembrane conductance regulator (CFTR). This protein belongs to the large ATP
      binding cassette (ABC) family of transporters. Most patients with cystic fibrosis
      bear a mutation in the nucleotide-binding domain 1 (NBD1) of CFTR, which plays a
      key role in the activation of the channel function of CFTR. Determination of the
      three dimensional structure of NBD1 is essential to better understand its
      structure-function relationship, and relate it to the biological features of
      CFTR. In this paper, we report the first preparation of recombinant His-tagged
      NBD1, as a soluble, stable and isolated domain. The method avoids the use of
      renaturing processes or fusion constructs. ATPase activity assays show that the
      recombinant domain is functional. Using tryptophan intrinsic fluorescence, we
      point out that the local conformation, in the region of the most frequent
      mutation DeltaF508, could differ from that of the nucleotide-binding subunit of
      histidine permease, the only available ABC structure. We have undertaken three
      dimensional structure determination of NBD1, and the first two dimensional 15N-1H
      NMR spectra demonstrate that the domain is folded. The method should be
      applicable to the structural studies of NBD2 or of other NBDs from different ABC
      proteins of major biological interest, such as multidrug resistance protein 1 or
      multidrug resistance associated protein 1.

PMID- 10951191
TI  - The antibiotic and anticancer active aurein peptides from the Australian Bell
      Frogs Litoria aurea and Litoria raniformis the solution structure of aurein 1.2.
AB  - Seventeen aurein peptides are present in the secretion from the granular dorsal
      glands of the Green and Golden Bell Frog Litoria aurea, and 16 from the
      corresponding secretion of the related Southern Bell Frog L. raniformis. Ten of
      these peptides are common to both species. Thirteen of the aurein peptides show
      wide-spectrum antibiotic and anticancer activity. These peptides are named in
      three groups (aureins 1-3) according to their sequences. Amongst the more active
      peptides are aurein 1.2 (GLFDIIKKIAESF-NH2), aurein 2.2 (GLFDIVKKVVGALGSL-NH2)
      and aurein 3.1 (GLFDIVKKIAGHIAGSI-NH2). Both L. aurea and L. raniformis have
      endoproteases that deactivate the major membrane-active aurein peptides by
      removing residues from both the N- and C-termini of the peptides. The most
      abundant degradation products have two residues missing from the N-terminal end
      of the peptide. The solution structure of the basic peptide, aurein 1.2, has been
      determined by NMR spectroscopy to be an amphipathic alpha-helix with well-defined
      hydrophilic and hydrophobic regions. Certain of the aurein peptides (e.g. aureins
      1.2 and 3.1) show anticancer activity in the NCI test regime, with LC50 values in
      the 10-5-10-4 M range. The aurein 1 peptides have only 13 amino-acid residues:
      these are the smallest antibiotic and anticancer active peptides yet reported
      from an anuran. The longer aurein 4 and 5 peptides, e.g. aurein 4.1
      (GLIQTIKEKLKELAGGLVTGIQS-OH) and aurein 5. 1 (GLLDIVTGLLGNLIVDVLKPKTPAS-OH) show
      neither antibacterial nor anticancer activity.

PMID- 10951193
TI  - Relating multidrug resistance phenotypes to the kinetic properties of their drug
      efflux pumps.
AB  - The simplest model for pump-mediated multidrug resistance is elaborated
      quantitatively. The way in which toxicity data should be evaluated to
      characterize most effectively the drug-efflux pump is then examined. The isotoxic
      drug dose (D10) depends on too many unrelated properties. The D10 of a cell line
      taken relative to that of the parental (nonresistant) cell line has been called
      the relative resistance (RR). This is inappropriate for characterizing the drug
      pump, as it depends on the extent of amplification of the latter. The reduced RR
      (RRR) is newly defined as the ratio of the (RR - 1) for one drug to the (RR - 1)
      for a different drug. This RRR should be independent of both the drug-target
      affinity and the extent of amplification of the drug pump in cell lines belonging
      to a family. The RRR depends on the avidities with which the pump extrudes the
      drugs relative to the passive membrane permeabilities of the latter. In plots of
      RRR for one drug combination vs. that for a second drug combination, cell lines
      that have the same pump amplified should cluster, whereas those with
      amplification of (functionally) different drug-efflux pumps should segregate.
      Both a set of new experimental data and literature results are discussed in terms
      of RRR. RRRs discriminate between human MDR1 and mouse mdr1a and mdr1b, between
      hamster pgp1 and a mutant thereof, as well as between human MDR1 and a mutant
      thereof. RRRs are not affected by changes in membrane surface area. Our results
      indicate that RRR may be used to (a) characterize drug-resistance mechanisms and
      (b) determine which drug-resistance mechanism is operative. Moreover, our
      analysis suggests that some of the reported phenotypic diversity among multidrug
      resistant cell lines may not be due to diversity in the resistance mechanism.

PMID- 10951192
TI  - Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on
      protein dynamics.
AB  - The structure of a recently reported neurotrophic ligand, 3-(3-pyridyl)-1
      propyl(2S)-1-(3,3-dimethyl-1, 2-dioxopentyl)-2-pyrrolidinecarboxylate, in complex
      with FKBP12 was determined using heteronuclear NMR spectroscopy. The inhibitor
      exhibits a binding mode analogous to that observed for the macrocycle FK506, used
      widely as an immunosuppressant, with the prolyl ring replacing the pipecolyl
      moiety and the amide bond in a trans conformation. However, fewer favourable
      protein-ligand interactions are detected in the structure of the complex,
      suggesting weaker binding compared with the immunosuppressant drug. Indeed, a
      micromolar dissociation constant was estimated from the NMR ligand titration
      profile, in contrast to the previously published nanomolar inhibition activity.
      Although the inhibitor possesses a remarkable structural simplicity with respect
      to FK506, 15N relaxation studies show that it induces similar effects on the
      protein dynamics, stabilizing the conformation of solvent-exposed residues which
      are important for mediating the interaction of immunophilin/ligand complexes with
      molecular targets and potentially for the transmission of the neurotrophic action
      of FKBP12 inhibitors.

PMID- 10951194
TI  - Evaluating limited specificity of drug pumps reduced relative resistance in human
      MDR phenotypes.
AB  - In the parallel paper, we developed a property to characterize drug efflux pumps,
      i.e. the reduced relative resistance (RRR). Using this RRR, we here investigate
      whether the observed diversity in human multidrug resistance (MDR) phenotypes
      might be due to variable levels of P-glycoprotein encoded by MDR1. We analyzed
      resistance phenotypes of various human cell lines in which either one, or both,
      classical human multidrug resistance genes, MDR1 and MDR3, are overexpressed. In
      addition, RRR values were calculated for MDR phenotypes presented in the
      literature. The results suggest that more than a single mechanism is required to
      account for the observed phenotypic diversity of classical multidrug resistance.
      This diversity is only partly due to differences in plasma membrane
      permeabilities between cell line families. It is discussed whether the
      alternative MDR phenotypes might be MDR1 phenotypes modified by other factors
      that do not themselves cause MDR. The method we here apply may also be useful for
      other nonspecific enzymes or pumps.

PMID- 10951195
TI  - O-glycosylation of insulin-like growth factor (IGF) binding protein-6 maintains
      high IGF-II binding affinity by decreasing binding to glycosaminoglycans and
      susceptibility to proteolysis.
AB  - Insulin-like growth factor binding protein-6 (IGFBP-6) is an O-linked
      glycoprotein which specifically inhibits insulin-like growth factor (IGF)-II
      actions. The effects of O-glycosylation of IGFBP-6 on binding to
      glycosaminoglycans and proteolysis, both of which reduce the IGF binding affinity
      of other IGFBPs were studied. Binding of recombinant human nonglycosylated (n-g)
      IGFBP-6 to a range of glycosaminoglycans in vitro was approximately threefold
      greater than that of glycosylated (g) IGFBP-6. When bound to glycosaminoglycans,
      IGFBP-6 had approximately 10-fold reduced binding affinity for IGF-II.
      Exogenously added n-gIGFBP-6 but not gIGFBP-6 also bound to partially purified
      rat PC12 phaeochromocytoma membranes. Binding of n-gIGFBP-6 was inhibited by
      increasing salt concentrations, which is typical of glycosaminoglycan
      interactions. O-glycosylation also protected human IGFBP-6 from proteolysis by
      chymotrypsin and trypsin. Proteolysis decreased the binding affinity of IGFBP-6
      for IGF-II, even with a relatively small reduction in apparent molecular mass as
      observed with chymotrypsin. Analysis by ESI-MS of IGFBP-6 following limited
      chymotryptic digestion showed that a 4.5-kDa C-terminal peptide was removed and
      peptide bonds involved in the putative high affinity IGF binding site were
      cleaved. The truncated, multiply cleaved IGFBP-6 remained held together by
      disulphide bonds. In contrast, trypsin cleaved IGFBP-6 in the mid-region of the
      molecule, resulting in a 16-kDa C-terminal peptide which did not bind IGF-II.
      These results indicate that O-glycosylation inhibits binding of IGFBP-6 to
      glycosaminoglycans and cell membranes and inhibits its proteolysis, thereby
      maintaining IGFBP-6 in a high-affinity, soluble form and so contributing to its
      inhibition of IGF-II actions.

PMID- 10951196
TI  - The structure of a complex glycosylphosphatidyl inositol-anchored glucoxylan from
      the kinetoplastid protozoan Leptomonas samueli.
AB  - The structure of a glycosylphosphatidyl inositol-anchored glucoxylan (GPI
      glucoxylan) synthesized by the monogenetic trypanosomatid Leptomonas samueli has
      been determined. The glucoxylan is anchored to the membrane by phytoceramide and
      an oligosaccharide core, the structure of which is identical to
      glycoinositolphospholipids (GIPLs) expressed by this protozoan. The glucoxylan
      chain is linear, containing -->4Glcalpha1-->, -->4Xylbeta1--> and -->3Xylbeta1-->
      residues. A well defined sequence heterogeneity was analysed in terms of a series
      of overlapping trisaccharide substructures. A proportion of the chains are capped
      with a GlcAalpha1-->3Glcalpha1--> sequence. While an average GlcA-capped chain
      contained 10 Glc and 16 Xyl residues, uncapped chains have a higher molecular
      mass with an average of 30 Glc and 50 Xyl per chain. We propose a mode of
      biosynthesis based on the observed structural heterogeneity.

PMID- 10951197
TI  - A novel hemocyte-specific membrane protein of Sarcophaga (flesh fly).
AB  - Extensive tissue remodeling takes place during metamorphosis of holometabolous
      insects. It has been shown that hemocytes play crucial roles in the recognition
      and elimination of apoptotic cells and larval tissue fragments produced during
      metamorphosis. We report the immunoaffinity purification, cDNA cloning, and
      characterization of a prepupal hemocyte membrane protein of Sarcophaga (flesh
      fly) with a molecular mass of 120 kDa. This protein is a novel type I
      transmembrane protein with 18 repeats of an epidermal growth factor-like domain
      in the predicted extracellular region. Expression of the protein was restricted
      exclusively to prepupal hemocytes. This protein is suggested to be a scavenger
      receptor for tissue remodeling.

PMID- 10951198
TI  - Biochemical characterization of human cathepsin X revealed that the enzyme is an
      exopeptidase, acting as carboxymonopeptidase or carboxydipeptidase.
AB  - Cathepsin X, purified to homogeneity from human liver, is a single chain
      glycoprotein with a molecular mass of approximately 33 kDa and pI 5.1-5.3.
      Cathepsin X was inhibited by stefin A, cystatin C and chicken cystatin (Ki = 1.7
      15.0 nM), but poorly or not at all by stefin B (Ki > 250 nM) and L-kininogen,
      respectively. The enzyme was also inhibited by two specific synthetic cathepsin B
      inhibitors, CA-074 and GFG-semicarbazone. Cathepsin X was similar to cathepsin B
      and found to be a carboxypeptidase with preference for a positively charged Arg
      in P1 position. Contrary to the preference of cathepsin B, cathepsin X normally
      acts as a carboxymonopeptidase. However, the preference for Arg in the P1
      position is so strong that cathepsin X cleaves substrates with Arg in
      antepenultimate position, acting also as a carboxydipeptidase. A large
      hydrophobic residue such as Trp is preferred in the P1' position, although the
      enzyme cleaved all P1' residues investigated (Trp, Phe, Ala, Arg, Pro). Cathepsin
      X also cleaved substrates with amide-blocked C-terminal carboxyl group with rates
      similar to those of the unblocked substrates. In contrast, no endopeptidase
      activity of cathepsin X could be detected on a series of o-aminobenzoic acid
      peptidyl-N-[2,-dinitrophenyl]ethylenediamine substrates. Furthermore, the
      standard cysteine protease methylcoumarine amide substrates (kcat/Km
      approximately 5.0 x 103 M-1.s-1) were degraded approximately 25-fold less
      efficiently than the carboxypeptidase substrates (kcat/Km approximately 120.0 x
      103 M-1.s-1).

PMID- 10951199
TI  - epsilon-crystallin from duck eye lens comparison of its quaternary structure and
      stability with other lactate dehydrogenases and complex formation with alpha
      crystallin.
AB  - Taxon-specific epsilon-crystallin (epsilonC) from duck eye lens is identical to
      duck heart muscle lactate dehydrogenase. It forms a dimer of dimers with a
      dissociation constant of 2.2 x 10-7 M, far beyond the value observed for other
      vertebrate lactate dehydrogenases. Comparing the characteristics of wild-type
      epsilon-crystallin with those of three mutants, G115N, G119F and 115N/119F,
      representing the only significant peripheral sequence variations between duck
      epsilonC and chicken or pig heart muscle lactate dehydrogenase, no significant
      conformational differences are detectable. Regarding the catalytic properties,
      the Michaelis constant of the double mutant 115N/119F for pyruvate is found to be
      decreased; for wild-type enzyme, the effect is overcompensated by the high
      expression level of epsilonC in the eye lens. As taken from spectral analysis of
      the guanidine-induced and temperature-induced denaturation transitions, epsilonC
      in its dimeric state is relatively unstable, whereas the native tetramer exhibits
      the high intrinsic stability characteristic of common vertebrate heart and muscle
      lactate dehydrogenases. The denaturation mechanism of epsilonC is complex and
      only partially reversible. In the case of thermal unfolding, the predominant side
      reaction competing with the reconstitution of the native state is the kinetic
      partitioning between proper folding and aggregation. alpha-Crystallin, the major
      molecular chaperone in the eye lens, inhibits the aggregation of epsilonC by
      trapping the misfolded protein.

PMID- 10951200
TI  - Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment
      of mammalian cell cytotoxicity.
AB  - We show here the identity of Alamar Blue as resazurin. The 'resazurin reduction
      test' has been used for about 50 years to monitor bacterial and yeast
      contamination of milk, and also for assessing semen quality. Resazurin (blue and
      nonfluorescent) is reduced to resorufin (pink and highly fluorescent) which is
      further reduced to hydroresorufin (uncoloured and nonfluorescent). It is still
      not known how this reduction occurs, intracellularly via enzyme activity or in
      the medium as a chemical reaction, although the reduced fluorescent form of
      Alamar Blue was found in the cytoplasm and of living cells nucleus of dead cells.
      Recently, the dye has gained popularity as a very simple and versatile way of
      measuring cell proliferation and cytotoxicity. This dye presents numerous
      advantages over other cytotoxicity or proliferation tests but we observed several
      drawbacks to the routine use of Alamar Blue. Tests with several toxicants in
      different cell lines and rat primary hepatocytes have shown accumulation of the
      fluorescent product of Alamar Blue in the medium which could lead to an
      overestimation of cell population. Also, the extensive reduction of Alamar Blue
      by metabolically active cells led to a final nonfluorescent product, and hence an
      underestimation of cellular activity.

PMID- 10951201
TI  - Oct-1 specifically binds the UEF4 site of the human AP1-regulated urokinase
      enhancer.
AB  - The inducible urokinase enhancer contains three essential elements: a combined
      PEA3/AP1 and a downstream AP1 site, separated by a 74-bp DNA region called COM
      (cooperation mediator), that is required for the synergism between the three
      sites. The 5' half of COM (uCOM) forms four retarded complexes with HeLa or HepG2
      nuclear proteins (UEF1-4). We now demonstrate that the UEF4 complex is the
      transcription factor Oct-1. Because of functional redundancy of the UEF sites,
      single mutations in UEF4 have no phenotype; we have changed UEF4 from a low to a
      high affinity binding site for Oct-1. In vitro, this mutation increases the DNA
      binding of Oct-1 and disturbs the binding of the Prep-Pbx complexes to the nearby
      UEF3 site. In vivo, this mutation reduces the basal transcriptional activity of
      the urokinase enhancer, while not affecting its phorbol ester inducibility. This
      is in keeping with the effect of the deletions of the COM region, which result in
      an increase in the basal level and, as a consequence, in the loss of 4beta
      phorbol 12-myristate 13-acetate inducibility. Oct-1 therefore is not involved in
      the inducibility of the urokinase enhancer but only in determining its basal
      activity level.

PMID- 10951202
TI  - Structure and expression of the mouse gene encoding the endozepine-like peptide
      from haploid male germ cells.
AB  - The endozepine-like peptide (ELP) represents a testis-specific isoform of the
      ubiquitous acyl-CoA binding protein (ACBP) and is highly expressed in late
      haploid stages of male germ cell development. The genomic sequence of the
      functional ELP gene as well as that of a pseudogene were analysed from
      independent bacteriophage clones of a 129sv mouse genomic library. Unlike the
      ACBP gene, which comprises four exons, the ELP gene has only a single intron
      within the region of the 5' untranslated region, suggesting that, like some other
      haploid expressed genes, the ELP gene might have evolved by retroposon-mediated
      gene duplication. Primer extension analysis was used to define the start site for
      transcription and hence the 5' promoter region. Electrophoretic mobility shift
      analysis was carried out on this region comparing nuclear extracts from adult
      mouse testis with those from mouse liver. Several testis-specific DNA-protein
      complexes were observed throughout 700 bp upstream of the transcription start
      site. One of these could be identified as corresponding to a steroidogenic factor
      1 (SF-1) binding element. Further analysis using pure transcription factors
      showed that this element at position -340 was able to bind specifically to both
      SF-1 and to the germ cell nuclear factor (GCNF). Immunohistochemical analysis
      using an ELP-specific antibody showed that expression was very restricted within
      the testis to the postmeiotic germ cells, and in the ovary to interstitial/luteal
      cells, cell-types known to express GCNF and SF-1, respectively. Testes of CREM
      tau knockout mice, lacking all spermatogenic stages later than round spermatids,
      were devoid of ELP immunoreactivity, whereas in RAD6 knockout mice the few
      remaining elongated spermatids were clearly defined by this excellent late
      haploid marker product. The ELP gene and its product thus offer an ideal system
      with which to investigate the differentiation of late haploid stages of
      spermatogenesis.

PMID- 10951203
TI  - Interaction of antimony tartrate with the tripeptide glutathione implication for
      its mode of action.
AB  - The tripeptide glutathione (gamma-L-Glu-L-Cys-Gly, GSH) is thought to play an
      important role in the biological processing of antimony drugs. We have studied
      the complexation of the antileishmanial drug potassium antimony(III) tartrate to
      GSH in both aqueous solution and intact red blood cells by NMR spectroscopy and
      electrospray ionization mass spectrometry. The deprotonated thiol group of the
      cysteine residue is shown to be the only binding site for Sb(III), and a complex
      with the stoichiometry [Sb(GS)3] is formed. The stability constant for [Sb(GS)3]
      was determined to be log K 25 (I = 0.1 M, 298 K) based on a competition reaction
      between tartrate and GSH at different pH* values. In spite of being highly
      thermodynamically stable, the complex is kinetically labile. The rate of exchange
      of GSH between its free and Sb-bound form is pH-dependent, ranging from slow
      exchange on the 1H-NMR timescale at low pH (2 s-1 at pH 3.2) to relatively rapid
      exchange at biological pH (> 440 s-1). Such facile exchange may be important in
      the transport of Sb(III) in various biofluids and tissues in vivo. Our spin-echo
      1H-NMR data show that Sb(III) rapidly entered red blood cell walls and was
      complexed by intracellular glutathione.

PMID- 10951204
TI  - Comparative analyses of secondary gene products of 3-deoxy-D-manno-oct-2-ulosonic
      acid transferases from Chlamydiaceae in Escherichia coli K-12.
AB  - The waaA gene encoding the essential, lipopolysaccharide (LPS)-specific 3-deoxy
      Dmanno-oct-2-ulosonic acid (Kdo) transferase was inactivated in the chromosome of
      a heptosyltransferase I and II deficient Escherichia coli K-12 strain by
      insertion of gene expression cassettes encoding the waaA genes of Chlamydia
      trachomatis, Chlamydophila pneumoniae or Chlamydophila psittaci. The three
      chlamydial Kdo transferases were able to complement the knockout mutation without
      changing the growth or multiplication behaviour. The LPS of the mutants were
      serologically and structurally characterized in comparison to the LPS of the
      parent strain using compositional analyses, high performance anion exchange
      chromatography, matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry and specific monoclonal antibodies. The data show that chlamydial
      Kdo transferases can replace in E. coli K-12 the host's Kdo transferase and
      retain the product specificities described in their natural background. In
      addition, we unequivocally proved that WaaA from C. psittaci transfers
      predominantly four Kdo residues to lipid A, forming a branched tetrasaccharide
      with the structure alpha-Kdo-(2-->8)-[alpha-Kdo-(2-->4)]-alpha-Kdo-(2-->4)-alpha
      Kdo.

PMID- 10951205
TI  - Mitochondrial and submitochondrial localization of human deoxyguanosine kinase.
AB  - Deoxyguanosine kinase and thymidine kinase 2 are responsible for catalysing the
      first step in the salvage of deoxynucleosides in mitochondria. These enzymes also
      play an important role in activating several antiviral and anticancer nucleoside
      analogs, which may lead to unwanted side-effects when the resulting nucleotides
      are incorporated into the mitochondrial genome. We studied deoxyguanosine kinase
      in submitochondrial fractions from human placental mitochondria. It was localized
      in the mitochondrial matrix fraction by Western blotting using a purified
      polyclonal antibody. This antibody was also used in an immunohistochemical in
      situ experiment with human embryonic kidney 293 cells, in which the
      deoxyguanosine kinase antibody colocalized with a mitochondrion-specific
      fluorescent probe and there was no significant cytosolic staining.

PMID- 10951206
TI  - Expression of the gene and processed pseudogenes encoding the human and rabbit
      translationally controlled tumour protein (TCTP).
AB  - In humans and rabbits, the TPT1 gene encoding the translationally controlled
      tumour protein TCTP generates two mRNAs (TCTP mRNA1 and TCTP mRNA2) which differ
      in the length of their 3' untranslated regions. The distribution of these mRNAs
      was investigated in 10 rabbit and 50 human tissues. They were transcribed in all
      tissues investigated, but differed considerably in their quantity and ratio of
      expression. This indicates an extensive transcriptional control and involvement
      of tissue-specific factors. In the rabbit genome numerous processed, intronless
      pseudogenes were detected. Four, corresponding to both types of mRNAs, were
      sequenced and analysed in detail; all displayed only few mutations and were
      either preserved completely in the original amino acid sequence of the intron
      containing gene, or contained only minor mutations in the coding region which did
      not interrupt the open reading frame. In the mRNA population of rabbit
      reticulocytes two additional TCTP RNAs of the TCTP mRNA2 type were detected,
      which have the characteristics of pseudogene transcripts. Pseudogene
      transcription was supported further by CAT reporter gene assays showing
      substantial promoter activity of 5'-flanking regions of two TPT1 pseudogenes.

PMID- 10951207
TI  - A novel type of carbohydrate-protein linkage region in the tyrosine-bound S-layer
      glycan of Thermoanaerobacterium thermosaccharolyticum D120-70.
AB  - The surface-layer (S-layer) protein of Thermoanaerobacterium
      thermosaccharolyticum D120-70 contains glycosidically linked glycan chains with
      the repeating unit structure -->4)[alpha-D-Galp-(1-->2)]-alpha-L-Rhap-(1-
      >3)[beta-D-Glcp-(1--> 6)] -beta-D-Manp-(1-->4)-alpha-L-Rhap-(1-->3)-alpha-D-Glcp
      (1--> . After proteolytic degradation of the S-layer glycoprotein, three
      glycopeptide pools were isolated, which were analyzed for their carbohydrate and
      amino-acid compositions. In all three pools, tyrosine was identified as the amino
      acid constituent, and the carbohydrate compositions corresponded to the above
      structure. Native polysaccharide PAGE showed the specific heterogeneity of each
      pool. For examination of the carbohydrate-protein linkage region, the S-layer
      glycan chain was partially hydrolyzed with trifluoroacetic acid. 1D and 2D NMR
      spectroscopy, including a novel diffusion-edited difference experiment, showed
      the O-glycosidic linkage region beta-D-glucopyranose-->O-tyrosine. No evidence
      was found of additional sugars originating from a putative core region between
      the glycan repeating units and the S-layer polypeptide. For the determination of
      chain-length variability in the S-layer glycan, the different glycopeptide pools
      were investigated by matrix-assisted laser desorption ionization-time of flight
      mass spectrometry, revealing that the degree of polymerization of the S-layer
      glycan repeats varied between three and 10. All masses were assigned to multiples
      of the repeating units plus the peptide portion. This result implies that no core
      structure is present and thus supports the data from the NMR spectroscopy
      analyses. This is the first observation of a bacterial S-layer glycan without a
      core region connecting the carbohydrate moiety with the polypeptide portion.

PMID- 10951208
TI  - Purification, characterization, cDNA cloning and expression of a novel
      ketoreductase from Zygosaccharomyces rouxii.
AB  - A novel ketoreductase isolated from Zygosaccharomyces rouxii catalyzes the
      asymmetric reduction of selected ketone substrates of commercial importance. The
      37.8-kDa ketoreductase was purified more than 300-fold to > 95% homogeneity from
      whole cells with a 30% activity yield. The ketoreductase functions as a monomer
      with an apparent Km for 3,4-methylenedioxyphenyl acetone of 2.9 mM and a Km for
      NADPH of 23.5 microM. The enzyme is able to effectively reduce alpha
      ketolactones, alpha-ketolactams, and diketones. Inhibition is observed in the
      presence of diethyl pyrocarbonate, suggesting that a histidine is crucial for
      catalysis. The 1.0-kb ketoreductase gene was cloned and sequenced from a Z.
      rouxii cDNA library using a degenerate primer to the N-terminal sequence of the
      purified protein. Furthermore, it was expressed in both Escherichia coli and
      Pichia pastoris and shown to be active. Substrate specificity, lack of a
      catalytic metal, and extent of protein sequence identity to known reductases
      suggests that the enzyme falls into the carbonyl reductase enzyme class.

PMID- 10951209
TI  - Structure elucidation and biological activity of an unusual adipokinetic hormone
      from corpora cardiaca of the butterfly, Vanessa cardui.
AB  - A structurally unusual member of the adipokinetic hormone/red pigment
      concentrating hormone peptide family was isolated from corpora cardiaca of the
      painted lady butterfly, Vanessa cardui. Its primary structure was assigned by
      Edman degradation and nano-electrospray-time-of-flight mass spectrometry as
      pQLTFTSSWGGK (Vac-AKH). Vac-AKH represents the first 11mer and the first
      nonamidated peptide in this family. The peptide shows significant adipokinetic
      activity in adult specimens of V. cardui. Injection of 10 pmol of synthetic Vac
      AKH into 4-day-old decapitated males resulted in an approximately 150% increase
      of hemolymph lipids after 90 min. Half maximal adipokinetic activity was achieved
      with about 0. 1 pmol of Vac-AKH. During a 2-h incubation of corpora
      cardiaca/corpora allata complexes in medium containing 50 mM KCl, significant
      amounts of Vac-AKH were released from the glands.

PMID- 10951210
TI  - A bifunctional enzyme with lycopene cyclase and phytoene synthase activities is
      encoded by the carRP gene of Mucor circinelloides.
AB  - Using functional analyses in Escherichia coli and Mucor circinelloides, it has
      been shown that a single M. circinelloides gene (carRP) codes for a protein with
      two different enzymatic activities, lycopene cyclase and phytoene synthase, which
      are encoded by independent genes in organisms other than fungi. This gene was
      identified using complementation tests among different classes of carotenoid
      mutants of M. circinelloides. The carRP gene product contains two domains: the R
      domain is located at the N-terminus and determines lycopene cyclase activity; the
      P domain is located at the C-terminus and displays phytoene synthase activity.
      The R domain is functional even in the absence of the P domain, while the latter
      needs the proper R domain conformation to carry out its function. The carRP gene
      is closely linked to the phytoene dehydrogenase (carB) gene, and the promoter
      regions of both genes are located within only 446 bp. Northern analyses show a co
      ordinated regulation of the expression of both genes by blue light. Several
      motifs found in this promoter region suggest a bi-directional mode of
      transcription control.

PMID- 10951211
TI  - Unique poly(glycerophosphate) lipoteichoic acid and the glycolipids of a
      Streptococcus sp. closely related to Streptococcus pneumoniae.
AB  - The Streptococcus sp. studied here is closely related to Streptococcus pneumoniae
      with 98.6% 16S rRNA similarity and 65% DNA/DNA homology. We isolated the
      lipoteichoic acid and the membrane glycolipids whose structures were established
      using conventional procedures and NMR spectroscopy. The lipoteichoic acid
      contains a linear 1,3-linked poly(glycerophosphate) chain which is partly
      substituted with D-alanine ester and is phosphodiester-linked to O6 of beta-D
      Galf(1-->3)acyl2Gro. This lipoteichoic acid is the first example in which a
      monohexosylglycerol serves as the glycolipid anchor; and with an average chain
      length of 10 glycerophosphate residues it is the shortest known to date. MS
      analysis, applied for the first time to a native acylated lipoteichoic acid,
      revealed a continuous increase in chain length from seven to 17 glycerophosphate
      residues with a maximum at 10, and allowed identification of the fatty acid
      combinations. Membrane glycolipids consisted of beta-D-Galf(1-->3)acyl2Gro (9%),
      alpha-D-Glcp(1-->3)acyl2Gro (22%), alpha-D-Galp(1-->2)-alpha-D-Glcp(1-
      >3)acyl2Gro (64%) and alpha-D-Galp(1-->2)-(6-O-acyl)-alpha-D-Glcp(1-->3)acyl2Gro
      (5%). It is noteworthy that in lipoteichoic acid biosynthesis, Galfacyl2Gro, a
      less abundant membrane glycolipid, is selected as the lipid anchor. Despite the
      genetic relatedness to Streptococcus pneumoniae, the lipoteichoic acid structure
      is quite different to the complex structure of pneumococcal lipoteichoic acid [T.
      Behr et al. (1992) Eur. J. Biochem. 207, 1063-1075], thus providing an example
      that minor differences in DNA sequence exert major changes in macromolecular
      structure.

PMID- 10951212
TI  - Hypotonic cell swelling induces translocation of the alpha isoform of cytosolic
      phospholipase A2 but not the gamma isoform in Ehrlich ascites tumor cells.
AB  - We demonstrate that two isoforms of the cytosolic phospholipase A2, cPLA2alpha
      and cPLA2gamma, are present in Ehrlich ascites tumor cells. Both enzymes are
      almost uniformly distributed throughout the cells under control conditions, as
      visualized by laser-scanning confocal microscopy. Stimulation by either hypotonic
      cell swelling or addition of the Ca2+ ionophore A23187 results in translocation
      of cPLA2alpha, but not cPLA2gamma, to the nucleus, where it forms hot-spot-like
      clusters. Our group previously showed that release of radioactively labeled
      arachidonic acid, incorporated into the phospholipids of Ehrlich cells, was
      immediately and transiently increased on hypotonic cell swelling [Thoroed, S.M.,
      Lauritzen, L., Lambert, I.H., Hansen, H.S. & Hoffmann, E.K. (1997) J. Membr.
      Biol. 160, 47-58]. We now demonstrate that arachidonic acid is released from the
      nuclear fraction following hypotonic exposure. Stimulation of Ehrlich cells with
      A23187 also leads to an increase in arachidonic acid release from the nucleus.
      However, as hypotonic cell swelling is not accompanied by any detectable increase
      in intracellular concentration of free cytosolic Ca2+ ([Ca2+]i), stimulus-induced
      translocation of cPLA2alpha can also occur without elevation of [Ca2+]i. The
      stimulus-induced translocation of cPLA2alpha appears not to be prevented by
      inhibition of mitogen-activated protein (MAP) kinase activation, p38 MAP kinase,
      tyrosine kinases and protein kinase C, hence, phosphorylation is not crucial for
      the stimulus-induced translocation of cPLA2alpha. Disruption of F-actin did not
      affect the translocation process, thus, an intact F-actin cytoskeleton does not
      seem to be required for translocation of cPLA2alpha.

PMID- 10951213
TI  - The light-harvesting antenna of brown algae: highly homologous proteins encoded
      by a multigene family.
AB  - Accessory light-harvesting complexes (LHCFs) were isolated from the brown alga
      Laminaria saccharina. Complexes specifically associated with photosystem I or II
      are identical with each other with respect to molecular mass, isoelectric point
      and behavior on anion-exchange chromatography or non-denaturing isoelectric
      focusing. The purified complexes also have similar pigment composition and
      spectroscopic properties. It is concluded that LHC antennae associated with
      photosystem I or II cannot be distinguished biochemically. After screening of
      genomic and cDNA libraries produced from L. saccharina sporophytes, six lhcf
      genes were isolated. Sequence analysis of these lhcf genes showed a high level of
      homology between the encoded polypeptides. Comparisons with coding sequences of
      lhcf genes from Macrocystis pyrifera and expressed sequence tags from Laminaria
      digitata (two other Laminariales) indicated that these proteins are probably very
      similar in all brown algae. Another feature common to the lhcf genes
      characterized was the presence of an intron in the coding region corresponding to
      the plastid-targeting presequence. The sequence similarity extended to the 5' and
      3' UTRs of several genes. In spite of the common origin of the chloroplasts, no
      light-regulating elements involved in the expression of the genes encoding the
      higher-plant light-harvesting proteins has been found in the UTRs.

PMID- 10951214
TI  - Endoglin expression on human microvascular endothelial cells association with
      betaglycan and formation of higher order complexes with TGF-beta signalling
      receptors.
AB  - Transforming growth factor-beta (TGF-beta) plays an important role in
      angiogenesis and vascular function. Endoglin, a transmembrane TGF-beta binding
      protein, is highly expressed on vascular endothelial cells and is the target gene
      for the hereditary haemorrhagic telangiectasia type I (HHT1), a dominantly
      inherited vascular disorder. The specific function of endoglin responsible for
      HHT1 is believed to involve alterations in TGF-beta responses. The initial
      interactions on the cell surface between endoglin and TGF-beta receptors may be
      an important mechanism by which endoglin modulates TGF-beta signalling, and
      thereby responses. Here it is shown that on human microvascular endothelial
      cells, endoglin is co-expressed and is associated with betaglycan, a TGF-beta
      accessory receptor with which endoglin shares limited amino acid homology. This
      complex formation may occur in either a ligand-dependent or a ligand-independent
      manner. In addition, the occurrence of three higher order complexes containing
      endoglin, type II and/or type I TGF-beta receptors, on these cells is
      demonstrated. Our findings suggest that endoglin may modify TGF-beta signalling
      by interacting with both betaglycan and the TGF-beta signalling receptors at
      physiological receptor concentrations and ratios.

PMID- 10951215
TI  - Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L
      aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction
      studied with synthetic primers.
AB  - Biosynthesis of the cyanobacterial nitrogen reserve cyanophycin (multi-L-arginyl
      poly-L-aspartic acid) is catalysed by cyanophycin synthetase, an enzyme that
      consists of a single kind of polypeptide. Efficient synthesis of the polymer
      requires ATP, the constituent amino acids aspartic acid and arginine, and a
      primer like cyanophycin. Using synthetic peptide primers, the course of the
      biosynthetic reaction was studied. The following results were obtained: (a)
      sequence analysis suggests that cyanophycin synthetase has two ATP-binding sites
      and hence probably two active sites; (b) the enzyme catalyses the formation of
      cyanophycin-like polymers of 25-30 kDa apparent molecular mass in vitro; (c)
      primers are elongated at their C-terminus; (d) the constituent amino acids are
      incorporated stepwise, in the order aspartic acid followed by arginine, into the
      growing polymer. A mechanism for the cyanophycin synthetase reaction is proposed;
      (e) the specificity of the enzyme for its amino-acid substrates was also studied.
      Glutamic acid cannot replace aspartic acid as the acidic amino acid, whereas
      lysine can replace arginine but is incorporated into cyanophycin at a much lower
      rate.

PMID- 10951216
TI  - Characterization of two sulfurtransferase isozymes from Arabidopsis thaliana.
AB  - Sulfurtransferases transfer a sulfane atom from a donor substrate to a thiophilic
      acceptor molecule. Recently a sulfurtransferase specific for the substrate 3
      mercaptopyruvate was isolated from Arabidopsis thaliana [Papenbrock, J. &
      Schmidt, A. (2000) Eur. J. Biochem. 267, 145-154]. In this study a second
      sulfurtransferase from Arabidopsis was characterized and compared to the enzyme
      described previously. Sequences of the mature proteins had an identity of 77.7%.
      The plant sulfurtransferases formed a distinct group within the known eukaryotic
      sulfurtransferases. When Southern blots were hybridized with labelled cDNA
      fragments from each of the plant sulfurtransferases the same pattern of bands was
      obtained indicating the existence of only these two closely related
      sulfurtransferases. The new sulfurtransferase was expressed in Escherichia coli
      fused with an N-terminal His6-tag, purified and tested for enzyme activity. Like
      the first enzyme, the newly isolated protein preferred 3-mercaptopyruvate to
      thiosulfate as substrate. The Km of both enzymes determined for 3
      mercaptopyruvate and cyanide were almost identical. As a result of database
      searches it became obvious that sulfurtransferase proteins from higher plants
      showed high similarities to small senescence- and stress-induced proteins. To
      prove the involvement of sulfurtransferases in senescence-associated processes 3
      mercaptopyruvate sulfurtransferase activity was determined in crude protein
      extracts from Arabidopsis plants of different ages. 3-mercaptopyruvate
      sulfurtransferase activity and steady-state RNA levels of sulfurtransferases
      increased with increasing age. However, steady-state protein levels as measured
      by using an antibody against the sulfurtransferase protein expressed previously
      decreased. Putative roles of sulfurtransferases in senescence-associated
      processes are discussed.

PMID- 10951217
TI  - Changes induced by oxygen in rat liver proteins identified by high-resolution two
      dimensional gel electrophoresis.
AB  - Molecular oxygen (O2) regulates the expression of a variety of genes. Several of
      the proteins that respond to changes in oxygen concentration have been identified
      in a variety of cell lines. We extend these previous studies by analyzing the
      effect of oxygen on the entire protein expression profile of an intact organ
      using high-resolution two-dimensional gel electrophoresis. To this end, we used
      an isolated, in vitro perfused organ preparation to produce two groups of rat
      livers perfused with high (95% O2, 5% CO2) or low (95% N2, 5% CO2) oxygen
      concentrations. Using two-dimensional gel electrophoresis we compared the protein
      expression profiles of both groups of livers. Computer analysis of the files
      obtained after laser densitometry of the two-dimensional gels revealed two spots
      that were strongly up-regulated in high PO2 perfused livers compared with low PO2
      perfused livers. These spots were analyzed by peptide mass fingerprinting
      analysis. These spots were identified as arginase 1 (liver-type arginase; EC
      3.5.3.1) and mitochondrial enoyl-CoA hydratase 1 (EC 4.2.1.17). The possible role
      of these proteins in its new context of oxygen availability is discussed.

PMID- 10951218
TI  - Implications of the generation of reactive oxygen species by photoactivated
      calcein for mitochondrial studies.
AB  - Calcein is a fluorescent probe that is widely used in studies of cell viability
      and mitochondrial function by microscopy fluorescence imaging. It was found to
      have a strong photosensitizing action that prevalently involves the generation of
      reactive oxygen species (ROS). The photooxidation properties of calcein in
      solution were studied in the presence of histidine and tryptophan as oxidizable
      substrates. The photodegradation of histidine was mainly mediated by singlet
      oxygen (1O2), as shown by the inhibitory effect of sodium azide, a specific 1O2
      scavenger. On the other hand, mixed photosensitization mechanisms were present
      when tryptophan was used as the target of the calcein-stimulated photoprocess. In
      addition to 1O2, hydroxyl radicals and hydrogen peroxide were involved as
      reactive species, as shown by using mannitol and catalase as scavengers. The
      calcein-photosensitized alterations of mitochondria as a potential source of
      artifacts in confocal microscopy studies of cells were considered. Irradiation of
      isolated mitochondria with visible light (500-600 nm) in the presence of calcein
      induced opening of the permeability transition (PT) pore. The extent of the
      mitochondrial membrane photodamage, however, was modulated by the nature of the
      calcein environment. Thus, pore opening was triggered at short irradiation times
      and low dye concentrations when calcein was dissolved in the bulk medium. On the
      contrary, calcein concentrated in the matrix space was rather inefficient as
      photosensitizer even at concentrations 10 times higher than those present in the
      external medium.

PMID- 10951219
TI  - A fluorescence-quenched chitopentaose for the study of endo-chitinases and
      chitobiosidases.
AB  - A new fluorogenic substrate displaying intramolecular fluorescence energy
      transfer (FRET) has been synthetized from NI,NII,NIII, NIV-tetra-acetyl
      chitopentaose. Two molecules, a fluorophore (5-(2-aminoethyl) amino-1-naphtalene
      sulfonic acid; EDANS) and a quenching group (dimethylaminophenylazophenyl; DAB)
      were chemically introduced on to the chitopentaose, one at each end. Among eight
      enzymes tested, only endo-chitinase and chitobiosidase activities could be
      specifically assayed by monitoring the variation of fluorescence after enzymatic
      hydrolysis of this substrate. Chitobiases and N-acetyl-beta-glucosaminidases are
      not active on the compound, the presence of a bulky chromogenic group at the 2
      position of the nonreducing end of the subtrate preventing the binding and thus
      hydrolysis by these two exo-enzymes. The observation that chitobiosidases are
      able to hydrolyse a chitooligosaccharide functionalized on both extremities
      demonstrates the possibility of an endo-action for this class of chitinases,
      which are generally classified as exo-enzymes. This fluorogenic
      chitooligosaccharide should prove to be very useful for the detection and the
      convenient assay of chitinolytic activities at nanomolar concentrations.

PMID- 10951220
TI  - Human brain GABA transaminase tissue distribution and molecular expression.
AB  - Human brain gamma-aminobutyrate transaminase is differentially expressed in a
      tissue-specific manner. mRNA master dot-blot analysis for 50 different human
      tissues, including different brain regions and fetal tissues, provided a complete
      map of the tissue distribution. Genomic Southern analysis revealed that the gamma
      aminobutyrate transaminase gene is a single copy, at least 15 kb in size. In
      addition, human brain gamma-aminobutyrate transaminase cDNA was expressed in
      Escherichia coli using a pGEX expression vector system. Catalytically active
      gamma-aminobutyrate transaminase was expressed in large quantities and the
      purified recombinant enzyme had kinetic parameters that were indistinguishable
      from those isolated from other mammalian brains. The human enzyme was inactivated
      by a well-known antiepileptic drug vigabatrin. Values of Ki and kinact were 1 mM
      and 0.35 min-1, respectively. Results from inactivation kinetics suggested that
      human gamma-aminobutyrate transaminase is more sensitive to the vigabatrin drug
      than the enzyme isolated from bovine brain.

PMID- 10951221
TI  - Molecular characterization of dipeptidyl peptidase activity in serum: soluble
      CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides.
AB  - Dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) is a serine type protease with an
      important modulatory activity on a number of chemokines, neuropeptides and
      peptide hormones. It is also known as CD26 or adenosine deaminase (ADA; EC
      3.5.4.4) binding protein. DPPIV has been demonstrated on the plasmamembranes of T
      cells and activated natural killer or B cells as well as on a number of
      endothelial and differentiated epithelial cells. A soluble form of CD26/DPPIV has
      been described in serum. Over the past few years, several related enzymes with
      similar dipeptidyl peptidase activity have been discovered, raising questions on
      the molecular origin(s) of serum dipeptidyl peptidase activity. Among them
      attractin, the human orthologue of the mouse mahogany protein, was postulated to
      be responsible for the majority of the DPPIV-like activity in serum. Using ADA
      affinity chromatography, it is shown here that 95% of the serum dipeptidyl
      peptidase activity is associated with a protein with ADA-binding properties. The
      natural protein was purified in milligram quantities, allowing molecular
      characterization (N-terminal sequence, glycosylation type, CD-spectrum, pH and
      thermal stability) and comparison with CD26/DPPIV from other sources. The
      purified serum enzyme was confirmed as CD26.

PMID- 10951222
TI  - Purification, characterization and molecular modelling of two toxin-like proteins
      from the Androctonus australis Hector venom.
AB  - Two toxin-like proteins (AahTL1 and AahTL3) were purified from the venom of the
      scorpion Androctonus australis Hector (Aah). AahTL1 and AahTL3 are the first non
      toxic proteins cross-reacting with AahI toxins group which indicates that these
      proteins can be used as a model of vaccins. In order to study structure-function
      relationships, their complete amino-acid sequences (66 residues) were determined,
      by automated Edman degradation. They show more than 50% of similarity with both
      AahI and AahIII antimammal toxins. Three-dimensional structural models of AahTL1
      and AahTL3 constructed by homology suggest that the two proteins are structurally
      similar to antimammal scorpion alpha-toxins specific to voltage dependent Na+
      channels. The models showed also that amino-acid changes between potent Aah
      toxins and both AahTL1 and AahTL3 disrupt the electrostatic potential gradient at
      their surface preventing their interaction with the receptor, which may explain
      their non toxicity.

PMID- 10951223
TI  - Plant mercaptopyruvate sulfurtransferases: molecular cloning, subcellular
      localization and enzymatic activities.
AB  - Mercaptopyruvate sulfurtransferase (MST, EC 2.8.1.2) and thiosulfate
      sulfurtransferase (TST, rhodanese, EC 2.8.1.1) are evolutionarily related enzymes
      that catalyze the transfer of sulfur ions from mercaptopyruvate and thiosulfate,
      respectively, to cyanide ions. We have isolated and characterized two cDNAs,
      AtMST1 and AtMST2, that are Arabidopsis homologs of TST and MST from other
      organisms. Deduced amino-acid sequences showed similarity to each other, although
      MST1 has a N-terminal extension of 57 amino acids containing a targeting
      sequence. MST1 and MST2 are located in mitochondria and cytoplasm, respectively,
      as shown by immunoblot analysis of subcellular fractions and by green fluorescent
      protein (GFP) analysis. However, some regions of MST1 fused to GFP were found to
      target not only mitochondria, but also chloroplasts, suggesting that the regions
      on the targeting sequence recognized by protein import systems of mitochondria
      and chloroplasts are not identical. Recombinant proteins, expressed in
      Escherichia coli, exhibited MST/TST activity ratios determined from kcat/Km
      values of 11 and 26 for MST1 and MST2, respectively. This indicates that the
      proteins encoded by both AtMST1 and AtMST2 are MST rather than TST type. One of
      the hypotheses proposed so far for the physiological function of MST and TST
      concerns iron-sulfur cluster assembly. In order to address this possibility, a T
      DNA insertion Arabidopsis mutant, in which the AtMST1 was disrupted, was isolated
      by PCR screening of T-DNA mutant libraries. However, the mutation had no effect
      on levels of iron-sulfur enzyme activities, suggesting that MST1 is not directly
      involved in iron-sulfur cluster assembly.

PMID- 10951224
TI  - Monitoring of the internalization of neuropeptide Y on neuroblastoma cell line SK
      N-MC.
AB  - Neuropeptide Y (NPY) is an important neuromodulator in the central and peripheral
      nervous system. The peptide acts through different NPY receptor subtypes (Y1-Y5,
      y6) that belong to the family of G protein-coupled receptors. In general,
      cellular responses to prolonged exposure to agonists of G protein-coupled
      receptors are attenuated, often through internalization of the receptors and
      their bound ligands. In this study, a fluorescent labeled NPY derivative was
      synthesized and characterized to investigate the internalization of NPY in the
      human neuroblastoma cell line SK-N-MC. Internalization was proven by binding
      experiments and subsequent acidic washing as well as by direct visualization by
      means of confocal laser scanning microscopy. Approximately 20-30% of the
      fluorescent labeled NPY and a tritium-marked NPY were resistant to acid removal
      of cell surface-bound ligands indicating internalization. Extracellular
      fluorescent labeled NPY was found to be distributed heterogeneously in a
      clustered pattern, which suggests that the ligand-receptor complex is collected
      in pits and caveolae followed by endocytosis.

PMID- 10951225
TI  - ENDOR spectroscopic studies of stable semiquinone radicals bound to the
      Escherichia coli cytochrome bo3 quinol oxidase.
AB  - The putative oxidation of ubiquinol by the cytochrome bo3 terminal oxidase of
      Escherichia coli in sequential one-electron steps requires stabilization of the
      semiquinone. ENDOR spectroscopy has recently been used to study the native
      ubisemiquinone radical formed in the cytochrome bo3 quinone-binding site
      [Veselov, A.V., Osborne, J.P., Gennis, R.B. & Scholes, C.P. (2000) Biochemistry
      39, 3169-3175]. Comparison of these spectra with those from the decyl
      ubisemiquinone radical in vitro indicated that the protein induced large changes
      in the electronic structure of the ubisemiquinone radical. We have used quinone
      substitution experiments to obtain ENDOR spectra of ubisemiquinone,
      phyllosemiquinone and plastosemiquinone anion radicals bound at the cytochrome
      bo3 quinone-binding site. Large changes in the electronic structures of these
      semiquinone anion radicals are induced on binding to the cytochrome bo3 oxidase.
      The changes in electronic structure are, however, independent of the electronic
      structures of these semiquinones in vitro. Thus it is shown to be the structure
      of this binding site in the protein, not the covalent structure of the bound
      quinone, that determines the electronic structure of the protein-bound
      semiquinone.

PMID- 10951227
TI  - In this issue

PMID- 10951226
TI  - Inhibition of the vacuolar H+-ATPase perturbs the transport, sorting, processing
      and release of regulated secretory proteins.
AB  - Vacuolar H+-ATPases (V-ATPases) are multisubunit enzymes that acidify various
      intracellular organelles, including secretory pathway compartments. We have
      examined the effects of the specific V-ATPase inhibitor bafilomycin A1 (Baf) on
      the intracellular transport, sorting, processing and release of a number of
      neuroendocrine secretory proteins in primary Xenopus intermediate pituitary
      cells. Ultrastructural examination of Baf-treated intermediate pituitary cells
      revealed a reduction in the amount of small dense-core secretory granules and the
      appearance of vacuolar structures in the trans-Golgi area. Pulse-chase
      incubations in combination with immunoprecipitation analysis showed that in
      treated cells, the proteolytic processing of the newly synthesized prohormone
      proopiomelanocortin, prohormone convertase PC2 and secretogranin III (SgIII) was
      inhibited, and an intracellular accumulation of intact precursor forms and
      intermediate cleavage products became apparent. Moreover, we found that treated
      cells secreted considerable amounts of a PC2 processing intermediate and
      unprocessed SgIII in a constitutive fashion. Collectively, these data indicate
      that in the secretory pathway, V-ATPases play an important role in creating the
      microenvironment that is essential for proper transport, sorting, processing and
      release of regulated secretory proteins.

PMID- 10951229
TI  - SCORTEN: a severity-of-illness score for toxic epidermal necrolysis.
AB  - The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to
      develop and validate a specific severity-of-illness score for cases of toxic
      epidermal necrolysis admitted to a specialized unit and to compare it with the
      Simplified Acute Physiology Score and a burn scoring system. A sample of 165
      patients was used to develop the toxic epidermal necrolysis-specific severity-of
      illness score and evaluate the other scores, a sample of 75 for validation. Model
      development used logistic regression equations that were translated into
      probability of hospital mortality; validation used measures of calibration and
      discrimination. We identified seven independent risk factors for death and
      constituted the toxic epidermal necrolysis-specific severity-of-illness score:
      age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of
      epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose
      above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic
      epidermal necrolysis-specific severity-of-illness score point the odds ratio was
      3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) =
      elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis
      specific severity-of-illness score). Calibration demonstrated excellent agreement
      between expected (19. 6%) and actual (20%) mortality; discrimination was also
      excellent with a receiver operating characteristic area of 82%. The Simplified
      Acute Physiology Score and the burn score were also associated with mortality.
      The discriminatory powers were poorer (receiver operating characteristic area: 72
      and 75%) and calibration of the Simplified Acute Physiology Score indicated a
      poor agreement between expected (9.1%) and actual (26.7%) mortality. This study
      demonstrates that the risk of death of toxic epidermal necrolysis patients can be
      accurately predicted by the toxic epidermal necrolysis-specific severity-of
      illness score. The Simplified Acute Physiology Score and burn score appear to be
      less adequate.

PMID- 10951228
TI  - Death receptors in cutaneous biology and disease.
AB  - Death receptors are a growing family of transmembrane proteins that can detect
      the presence of specific extracellular death signals and rapidly trigger cellular
      destruction by apoptosis. Expression and signaling by death receptors and their
      respective ligands is a tightly regulated process essential for key physiologic
      functions in a variety of organs, including the skin. Several death receptors and
      ligands, Fas and Fas ligand being the most important to date, are expressed in
      the skin and have proven to be essential in contributing to its functional
      integrity. Recent evidence has shown that Fas-induced keratinocyte apoptosis in
      response to ultraviolet light, prevents the accumulation of pro-carcinogenic p53
      mutations by deleting ultraviolet-mutated keratinocytes. Further- more, there is
      strong evidence that dysregulation of Fas expression and/or signaling contributes
      to the pathogenesis of toxic epidermal necrolysis, acute cutaneous graft versus
      host disease, contact hypersensitivity and melanoma metastasis. With these new
      developments, strategies for modulating the function of death receptor signaling
      pathways have emerged and provided novel therapeutic possibilities. Specific
      blockade of Fas, for example with intravenous immunoglobulin preparations that
      contain specific anti-Fas antibodies, has shown great promise in the treatment of
      toxic epidermal necrolysis and may also be useful in the treatment acute graft
      versus host disease. Likewise, induction of death signaling by ultraviolet light
      can lead to hapten-specific tolerance, and gene transfer of Fas ligand to
      dendritic cells can be used to induce antigen specific tolerance by deleting
      antigen-specific T cells. Further developments in this field may have important
      clinical implications in cutaneous disease.

PMID- 10951230
TI  - Selective upregulation of fibroblast Fas ligand expression, and prolongation of
      Fas/Fas ligand-mediated skin allograft survival, by retinoic acid: the skin as a
      retinoide-inducible immune privilege site.
AB  - Fas/Fas ligand-mediated lymphocyte apoptosis has been implicated in the
      suppression of immune responses and may cause immune privilege. Human corneas
      exhibit immune privilege and can be transplanted across allogeneic barriers
      without immunosuppressive therapy, perhaps, because corneal keratinocytes express
      Fas ligand. To characterize Fas and Fas ligand expression in skin, we examined
      expression by murine keratinocytes, dermal fibroblasts, melanocytes, and human
      umbilical endothelial cells. We also studied the regulation of Fas and Fas ligand
      in skin cells by retinoic acid, vitamin D3, and dexamethasone as well as various
      cytokines. Among the molecules and cells tested, retinoic acid selectively
      upregulated the expression of Fas ligand molecule by fibroblasts. Retinoic acid
      induced Fas ligand+ fibroblasts killed Fas+ target cells, and this killing was
      blocked by anti-Fas ligand antibody. The function of Fas ligand on dermal
      fibroblasts in vivo was tested in a cutaneous allograft system. Histoincompatible
      BALB/C mouse (H-2d) donor skin was grafted on to allogeneic C57BL/6 mice (H-2b).
      Daily local injection of retinoic acid blocked inflammation and extended graft
      survival for more than 10 d. Injection of retinoic acid into Fas ligand mutated
      gld/gld donor skin did not prevent leukocyte infiltration into the allograft or
      prolong graft survival. These experiments indicate that, in skin, retinoic acid
      selectively increases Fas ligand expression by fibroblasts and that retinoic acid
      has potent Fas/Fas ligand-dependent immunosuppressive activity.

PMID- 10951231
TI  - Inhibition of melanosome transfer results in skin lightening.
AB  - The chemical basis of melanogenesis is well documented, but the mechanism of
      melanosome transfer and the regulation of pigmentation by keratinocyte-melanocyte
      interactions are not well understood. Therefore we examined the effects of serine
      protease inhibitors on skin pigmentation and found that the protease-activated
      receptor 2, expressed on keratinocytes, may regulate pigmentation via
      keratinocyte-melanocyte interactions. Here we show that modulation of protease
      activated receptor 2 activation affects melanosome transfer into keratinocytes,
      resulting in changes in pigment production and deposition. SLIGRL, the protease
      activated receptor 2 activating peptide, enhanced melanosome ingestion by
      keratinocytes, thus increasing pigment deposition. RWJ-50353, a serine protease
      inhibitor, led to reduced pigment deposition in melanocytes and depigmentation.
      Electron microscopy studies illustrated an accumulation of immature melanosomes
      inside melanocytes and abnormal dendrite dynamics in RWJ-50353-treated epidermal
      equivalents. RWJ-50353 induced a visible and dose-dependent skin lightening
      effect in the dark-skinned Yucatan swine. Examinations by electron microscopy
      indicated that the in vivo transfer of melanosomes from melanocytes to
      keratinocytes was affected. Our data suggest that modulation of keratinocyte
      melanocyte interactions via the protease-activated receptor 2 pathway affects
      melanosome transfer. The use of RWJ-50353 to modulate protease-activated receptor
      2 activation could lead to a new class of depigmenting agents.

PMID- 10951232
TI  - Chemical activation of innate and specific immunity in contact dermatitis.
AB  - Recent reports have suggested that chemical-induced allergic contact dermatitis
      may not be a traditional type IV hypersensitivity, in part due to the dual
      irritant and antigenic properties of sensitizing chemicals. In order to
      investigate the contribution of these properties to the molecular and cellular
      mechanism underlying allergic contact dermatitis, we evaluated oxazolone-induced
      changes in cell populations and cytokine production in the dermis of transgenic
      mice with impaired innate immunity (the FcgammaR subunit knockout mouse), and
      absent specific immunity (the athymic mouse), and the appropriate B6,129F2 and
      C57BL/6 control mice. Oxazolone and croton oil were applied in a single
      sensitizing dose, or in sensitizing and challenge doses, and the dermal response
      was evaluated by immunohistochemistry. In the wild type mice, with or without
      sensitization to oxazolone or croton oil, we observed mixed Th1/Th2 cytokine
      production and both CD4+ and CD8+ T lymphocytes; however, the neutrophil was the
      predominant cell in the dermis, even 72 h after final chemical application.
      Athymic mice displayed a similar neutrophil response with moderate Th1/Th2
      cytokine production, and FcgammaR subunit knockout mice exhibited very mild
      dermatitis when treated with either oxazolone or croton oil. These results
      provide support for the hypothesis that allergic contact dermatitis is not a
      classic delayed type hypersensitivity, demonstrate the importance of the
      interaction between the irritant and antigenic properties of sensitizing
      chemicals in the development of allergic contact dermatitis, and suggest that the
      irritant effect of chemicals may be mediated through the cutaneous innate immune
      system.

PMID- 10951233
TI  - Decreased extracellular-signal-regulated kinase and increased stress-activated
      MAP kinase activities in aged human skin in vivo.
AB  - The ability of human skin to rejuvenate itself diminishes with the passage of
      time, resulting in increased fragility. This increased fragility reflects both
      reduced growth of skin cells and loss of collagenous connective tissue. Oxidative
      damage plays a central role in cellular aging. Cellular responses to growth
      signals and oxidative stress are mediated, in part, by growth-factor-activated
      and stress-activated MAP kinases. We report here that the extracellular-signal
      regulated MAP kinase pathway is reduced and the stress-activated MAP kinase
      pathway is increased in old, compared with young, human skin in vivo.
      Extracellular-signal-regulated kinase activity was 45% lower in old skin (mean
      age 84.3 y) relative to young skin (mean age 23.8 y). This lower extracellular-
      signal-regulated kinase activity resulted from reduced activation, since total
      extracellular-signal-regulated kinase protein levels did not differ between young
      and old skin, whereas phosphorylated (i.e., activated) extracellular-signal
      regulated kinase protein was reduced 60% in old skin. Cyclin D2, which is
      regulated by extracellular-signal-regulated kinase and functions to promote cell
      cycle progression, was reduced 50% in old skin compared with young skin. In
      contrast, stress-activated MAP kinase activity was elevated 3.4-fold in old skin
      compared with young skin. This increased activity resulted from enhanced
      activation, since total stress-activated MAP kinase protein levels were similar
      in old and young skin. Transcription factor c-Jun, which is activated by stress
      activated MAP kinases and promotes expression of connective-tissue-degrading
      matrix metalloproteinases, was elevated 2-fold in old skin compared with young
      skin. Treatment of old skin with vitamin A (retinol) for 7 d stimulated
      extracellular-signal-regulated kinase activity, consistent with its demonstrated
      ability to stimulate cell growth in old human skin. Taken together, these data
      indicate that alterations in MAP kinase activities play a key role in the
      pathophysiology of human skin aging.

PMID- 10951234
TI  - Topical ALA-photodynamic therapy for the treatment of acne vulgaris.
AB  - Topical aminolevulinic acid is converted into a potent photosensitizer,
      protoporphyrin, in human hair follicles and sebaceous glands. Photodynamic
      therapy with topical aminolevulinic acid was tested for the treatment of acne
      vulgaris, in an open-label prospective human study. Each of 22 subjects with acne
      on the back was treated in four sites with aminolevulinic acid plus red light,
      aminolevulinic acid alone, light alone, and untreated control. Half of the
      subjects were treated once; half were treated four times. Twenty percent topical
      aminolevulinic acid was applied with 3 h occlusion, and 150 J per cm2 broad-band
      light (550-700 nm) was given. Sebum excretion rate and auto-fluorescence from
      follicular bacteria were measured before, and 2, 3, 10, and 20 wk after,
      treatment. Histologic changes and protoporphyrin synthesis in pilosebaceous units
      were observed from skin biopsies. Aminolevulinic acid plus red light caused a
      transient acne-like folliculitis. Sebum excretion was eliminated for several
      weeks, and decreased for 20 wk after photodynamic therapy; multiple treatments
      caused greater suppression of sebum. Bacterial porphyrin fluorescence was also
      suppressed by photodynamic therapy. On histology, sebaceous glands showed acute
      damage and were smaller 20 wk after photodynamic therapy. There was clinical and
      statistically significant clearance of inflammatory acne by aminolevulinic acid
      plus red light, for at least 20 wk after multiple treatments and 10 wk after a
      single treatment. Transient hyperpigmentation, superficial exfoliation, and
      crusting were observed, which cleared without scarring. Topical aminolevulinic
      acid plus red light is an effective treatment of acne vulgaris, associated with
      significant side-effects. Aminolevulinic acid plus red light causes phototoxicity
      to sebaceous follicles, prolonged suppression of sebaceous gland function, and
      apparent decrease in follicular bacteria after photodynamic therapy. Potentially,
      aminolevulinic acid plus red light may be useful for some patients with acne.

PMID- 10951235
TI  - Studies on epidermis reconstructed with and without melanocytes: melanocytes
      prevent sunburn cell formation but not appearance of DNA damaged cells in fair
      skinned caucasians.
AB  - To assess the photoprotective role of melanocytes in the epidermis, we studied
      the effects of ultraviolet B on an epidermis reconstructed with and without
      melanocytes. To address more specifically the role of melanin in fair-skinned
      individuals, experiments were done with cells obtained from human skin of low
      phototypes (II-III). To study the effect of constitutive melanin and possibly
      that of newly synthesized melanin precursors, a single dose of ultraviolet B
      (0.10 or 0.15 J per cm2, corresponding to a 4-5 minimal erythema dose in vivo)
      was administered to reconstructs and the effects were monitored over the first 24
      h. When reconstructs with and without melanocytes were compared, no difference
      was found for DNA damage/repair assessed with antibodies to cyclobutane
      pyrimidine dimers and 6-4 photoproducts. More necrotic/apoptotic cells, however,
      were noted 24 h following ultraviolet B irradiation in reconstructs lacking
      melanocytes. Twenty-four hours following ultraviolet B irradiation the number of
      necrotic/apoptotic cells and the number of cyclobutane pyrimidine dimer positive
      cells was coarsely concentration-dependent. The number of cyclobutane pyrimidine
      dimer positive cells, however, was independent of the type of reconstruct used
      (with/without melanocytes). In conclusion, low phototype melanocytes seem to
      protect epidermal basal cells against ultraviolet B-induced apoptosis/necrosis
      and may preserve the overall integrity of the epidermis after ultraviolet B
      irradiation. On the contrary, such melanocytes do not seem to have a protective
      role against DNA damage and may not prevent cancer.

PMID- 10951236
TI  - Histologic and cell kinetic studies of hair loss and subsequent recovery process
      of human scalp hair follicles grafted onto severe combined immunodeficient mice.
AB  - To establish a model for studying human scalp hair, individually isolated hair
      follicles were grafted onto back skin of severe combined immunodeficient mice.
      Histologic changes and cell kinetics in the hair loss and subsequent recovery
      process were investigated. In the dystrophic stage (from day 7 to 30), all the
      hair shafts became dystrophic and were shed. Thickening and corrugation of
      vitreous membrane, apoptosis, and regression of the lower part were observed in
      the grafted hair follicles. 5-bromo-2'-deoxy-uridine-labeled cells were not
      detected in the lower end of the follicles, and keratin 19-positive cells
      appeared there. At the end of this stage their lower part was maximally
      retracted, secondary germ remained beneath the bulge, and the vitreous membrane
      disappeared. In the regeneration stage (from day 30 to 50), the same histologic
      findings as those at the end of the dystrophic stage were observed. The keratin
      19-positive cells in the secondary germ, however, were replaced with keratin 19
      negative and 5-bromo-2'-deoxy-uridine-labeled cells. Then, differentiation into
      an inner root sheath and a hair shaft began, and apoptosis was terminated. In the
      stable growth stage (from day 40 to at least 150), the grafted follicles were
      immunohistochemically and light microscopically identical with the normal anagen
      hair follicles except for the presence of melanin incontinence. These findings
      suggest that the grafted hair follicles entered into dystrophic catagen,
      subsequently dystrophic telogen, then returned to normal anagen follicles, and
      that stem cells or their close progeny in the secondary germ play an important
      part in the recovery process.

PMID- 10951237
TI  - Hemizygosity for a glycine substitution in collagen XVII: unfolding and
      degradation of the ectodomain.
AB  - Defects of collagen XVII, a keratinocyte adhesion protein, are associated with
      epidermal detachment in junctional epidermolysis bullosa. Although some missense
      mutations in the collagen XVII gene COL17A1 have been described, the molecular
      mechanisms leading to disease have remained elusive in these cases. Here we
      assessed the biologic consequences of a missense mutation by studying the folding
      and stability of wild-type and mutated recombinant collagen XVII domains. The
      mutation occurred in a junctional epidermolysis bullosa patient who was compound
      heterozygous for the novel glycine substitution mutation G633D and the novel
      nonsense mutation R145X. Collagen XVII mRNA was significantly reduced, indicating
      nonsense-mediated mRNA degradation and hemizygosity of the patient for the G633D
      substitution. As glycine residues within the collagen triple helices are
      important for stable conformation, the thermal stability of the wild-type and
      mutated eukaryotic recombinant Col15 domain of collagen XVII was assessed. The
      stability of the mutated fragment was clearly reduced. The midpoint of the helix
      to-coil transition, Tm, was 5 degrees C lower than that of wild-type rCol15,
      indicating abnormal triple-helix folding and susceptibility to proteolysis.
      Consistently, immunoassays demonstrated reduced amounts of the full-length
      collagen XVII and absence of the soluble ectodomain in keratinocyte cultures, and
      lack of the ectodomain from the junctional epidermolysis bullosa skin. These
      observations show that the glycine substitution G633D in collagen XVII causes
      abnormal folding and susceptibility to degradation, and thus perturbs the
      physiologic adhesive functions of collagen XVII in the skin.

PMID- 10951238
TI  - Relationship between cell-associated matrix metalloproteinase 9 and psoriatic
      keratinocyte growth.
AB  - Primary cultures of psoriatic keratinocytes proliferated at a higher rate and
      produced lower amounts of matrix metalloproteinase 9 than normal keratinocytes
      cultured under similar conditions. Sup- plementation of psoriatic keratinocyte
      cell culture medium with batimastat or the use of a matrix metalloproteinase 9
      blocking antibody further stimulated psoriatic keratinocyte growth. An increase
      in intracellular ceramide level enhanced matrix metalloproteinase 9 production
      and inhibited cell proliferation in parallel. Whether cells were treated with
      sphingomyelinase or not, however, conditioned media from psoriatic keratinocytes
      contained higher levels of tissue inhibitor of metalloproteinase-1 compared with
      matrix metalloproteinase 9 and secreted only the proenzyme form. Pro-matrix
      metalloproteinase 9, as well as active matrix metalloproteinase 9, was identified
      in membrane preparations of psoriatic keratinocytes, and enzyme amounts were
      greatly elevated following sphingomyelinase action. As (i) tissue inhibitor of
      metalloproteinase-1 antibody nearly totally abrogated keratinocyte growth and
      (ii) complexes of tissue inhibitor of metalloproteinase-1 and matrix
      metalloproteinase 9 were recovered in membrane extracts of sphingomyelinase
      treated psoriatic keratinocytes, we postulate that an increased level of cell
      associated matrix metalloproteinase 9 might compete for tissue inhibitor of
      metalloproteinase-1 binding to its receptor. As a consequence, the increased
      levels of matrix metalloproteinase 9 will decrease keratinocyte growth.

PMID- 10951239
TI  - Keratinocytes express the CD146 (Muc18/S-endo) antigen in tissue culture and
      during inflammatory skin diseases.
AB  - The CD146 (or MUC18/MEL-CAM) antigen is a cell adhesion molecule of the
      immunoglobulin superfamily. Besides in melanoma, expression of CD146 antigen has
      been demonstrated in breast epithelia and hair follicles. We studied its
      expression by human keratinocytes in culture as well as in neoplastic and
      inflammatory skin diseases. Staining of primary cultured keratinocytes revealed
      expression of CD146 on the cell membrane, preferentially on cell-cell contact
      sites. Western blot analysis of keratinocytes detected a band of approximately
      113 kDa, corresponding to the CD146 protein. In contrast to primary
      keratinocytes, neither CD146 protein nor mRNA expression was found in the
      keratinocyte-derived cell lines A431 and HaCaT. Treatment of keratinocytes with
      the proinflammatory cytokines interleukin-1 and interleukin-6, tumor necrosis
      factor-alpha, and interferon-gamma, resulted in no change of CD146 expression and
      incubation with phorbol 12-myristate 13-acetate led to a reduction of CD146 on
      keratinocytes. By contrast, when culturing keratinocytes in medium devoid of
      growth supplements, a distinct upregulation was observed as compared with culture
      in fully supplemented medium. In normal human epidermis expression of the CD146
      antigen was not detectable. It was strongly upregulated, however, on suprabasal
      keratinocytes in psoriasis, in lichen planus, in the epidermis overlying skin
      neoplasms, and in viral warts. In squamous cell carcinomas and basal cell
      carcinomas only a minority of tumor cells expressed CD146. Our findings suggest
      that the CD146 antigen represents an activation marker of keratinocytes and may
      be involved in cutaneous inflammatory tissue reaction.

PMID- 10951240
TI  - Defective extracellular matrix reorganization by chronic wound fibroblasts is
      associated with alterations in TIMP-1, TIMP-2, and MMP-2 activity.
AB  - Chronic leg wounds are characterized by defective remodeling of the extracellular
      matrix, failure of reepithelialization, and prolonged inflammation. The
      hypothesis that this defective extracellular matrix remodeling is associated with
      phenotypic differences in the activity of the matrix metalloproteinases and
      tissue inhibitors of metalloproteinases was studied in chronic wound and patient
      matched normal fibroblasts in three-dimensional collagen lattice systems. Chronic
      wound fibroblasts exhibited no differences in morphology or proliferation (p >
      0.1) compared with patient-matched uninvolved dermal fibroblasts. The ability of
      chronic wound fibroblasts to reorganize extracellular matrix was significantly
      impaired, however, in comparison to the uninvolved dermal fibroblasts (p < 0.01).
      This difference in extracellular matrix reorganization was not related to
      differences in proliferation within the collagen lattices (p > 0.05) or
      attachment to type I collagen (p > 0.1). Marked differences were evident in
      matrix metalloproteinase-2 activity between chronic wound and patient-matched
      normal fibroblasts. Whereas levels of pro-matrix metalloproteinase-2 were similar
      between the two fibroblast populations (p > 0.1), the chronic wound fibroblasts
      exhibited significantly decreased levels of the 62 kDa active form of matrix
      metalloproteinase-2 (p < 0.01). Reverse zymography and enzyme-linked
      immunosorbent assay demonstrated that the decreased matrix metalloproteinase-2
      activity was associated with increased production of tissue inhibitors of
      metalloproteinase-1 and -2 by the chronic wound fibroblasts (p < 0.05). Increased
      production of tissue inhibitors of metalloproteinases in chronic wound
      fibroblasts was also reflected in decreased levels of matrix metalloproteinase-1
      (p < 0.005). These data suggest that the impaired ability of chronic wound
      fibroblasts to reorganize extracellular matrix in vitro is related to decreased
      levels of active matrix metalloproteinase-2 and matrix metalloproteinase-1
      resulting from increased production of tissue inhibitors of metalloproteinase-1
      and -2 by chronic wound fibroblasts. These findings provide a mechanism to
      explain the impaired cellular responses and extracellular matrix reorganization
      observed in chronic leg wounds in vivo.

PMID- 10951242
TI  - Large and sustained induction of chemokines during impaired wound healing in the
      genetically diabetic mouse: prolonged persistence of neutrophils and macrophages
      during the late phase of repair.
AB  - Chemokines are seen as the stimuli that largely control leukocyte migration. To
      assess whether the severely impaired process of cutaneous repair observed in
      genetically diabetic db/db mice is associated with a dysregulated infiltration of
      immune cells, we determined the expressional kinetics for the murine growth
      regulated oncogene/melanoma growth stimulatory activity homolog macrophage
      inflammatory protein-2, and the macrophage chemoattractant protein-1,
      respectively. Wound repair in db/db mice was characterized by a sustained
      inflammatory response and a prolonged expression of macrophage inflammatory
      protein-2 and macrophage chemoattractant protein-1. Immuno-histochemistry
      revealed that keratinocytes at the wound margins expressed macrophage
      chemoattractant protein-1, whereas macrophage inflammatory protein-2
      immunopositive signals were observed only in keratinocytes of hair follicles
      located adjacent to the wound site. Inactivation studies using neutralizing
      antibodies against macrophage chemoattractant protein-1 or macrophage
      inflammatory protein-2 indicated that sustained expression of these chemokines
      participated in a prolonged presence of neutrophils and macrophages at the wound
      site during diabetic repair. Furthermore, our data provide evidence that late
      infiltration (day 13 after injury) of neutrophils and macrophages into wounds in
      db/db mice was associated with a simultaneous downregulation of mRNA for
      receptors specific for macrophage inflammatory protein-2 and macrophage
      chemoattractant protein-1 in these animals.

PMID- 10951241
TI  - Delayed wound healing in CXCR2 knockout mice.
AB  - Previous studies demonstrated that the CXC chemokine, MGSA/GRO-alpha and its
      receptor, CXCR2, are expressed during wound healing by keratinocytes and
      endothelial cells at areas where epithelialization and neovascularization occur.
      The process of wound healing is dependent on leukocyte recruitment, keratinocyte
      proliferation and migration, and angiogenesis. These processes may be mediated in
      part by CXC chemokines, such as interleukin-8 and MGSA/GRO-alpha. To examine
      further the significance of CXC chemokines in wound healing, full excisional
      wounds were created on CXCR2 wild-type (+/+), heterozygous (+/-), or knockout (-/
      ) mice. Wounds were histologically analyzed for neutrophil and monocyte
      infiltration, neovascularization and epithelialization at days 3, 5, 7, and 10
      postwounding. The CXCR2 -/- mice exhibited defective neutrophil recruitment, an
      altered temporal pattern of monocyte recruitment, and altered secretion of
      interleukin-1beta. Significant delays in wound healing parameters, including
      epithelialization and decreased neovascularization, were also observed in CXCR2 
      /- mice. In vitro wounding experiments with cultures of keratinocytes established
      from -/- and +/+ mice revealed a retardation in wound closure in CXCR2 -/-
      keratinocytes, suggesting a role for this receptor on keratinocytes in epithelial
      resurfacing that is independent of neutrophil recruitment. These in vitro and in
      vivo studies further establish a pathophysiologic role for CXCR2 during cutaneous
      wound repair.

PMID- 10951243
TI  - Detection of expanded T cell clones in skin biopsy samples of patients with
      lichen sclerosus et atrophicus by T cell receptor-gamma polymerase chain reaction
      assays.
AB  - Lichen sclerosus et atrophicus is a chronic dermatosis of unknown etiology and
      pathogenesis. Lichen sclerosus et atrophicus associated skin lesions show T cell
      enriched infiltrates, sometimes resembling the histologic picture of early
      mycosis fungoides. It is supposed that the infiltrating T cells participate in
      the pathogenesis of atrophy and sclerosis. We investigated skin biopsies from 39
      lichen sclerosus et atrophicus patients by histology, immunohistochemistry and,
      in order to establish the status of T cell clonality, by polymerase chain
      reaction amplifying the T cell receptor-gamma rearrangements. A stage-dependent
      shift of the CD3-positive T cells was observed from a predominantly CD4-positive
      to a predominantly CD8-positive phenotype. The increase of CD8-positive cells was
      associated with more pronounced epidermotropism and basal degeneration. Nearly
      all CD8-positive cells expressed cytotoxic granules (TIA1), possibly causing the
      basal destruction. In the late fibrotic stage of the disease, only a weak or no
      infiltrate was found. Regarding the T cell receptor-gamma polymerase chain
      reaction, the presence of clonally expanded T cells was demonstrated in 19 of 39
      patients (49%) by at least one of two different high resolution electrophoresis
      techniques applied to separate the amplification products. Thus, for the first
      time clonally expanded infiltrating T cells were detected in lichen sclerosus et
      atrophicus. Furthermore, this is one of the first reports on the detection of
      clonally expanded infiltrating T cells in an inflammatory skin disease. The
      clonal T cells could not be assigned to the CD4 or CD8 subtype. Most likely,
      their presence is not the result of a malignant transformation but a response to
      an as yet unknown lichen sclerosus et atrophicus associated antigen.

PMID- 10951244
TI  - Peptide immunization indicates that CD8+ T cells are the dominant effector cells
      in trinitrophenyl-specific contact hypersensitivity.
AB  - The identity of the effector T cell population involved in contact
      hypersensitivity is still questionable with evidence promoting both CD4+ or CD8+
      T cells. Previous experimental studies have relied on the in vivo depletion of T
      cell subsets using antibody, or the use of knock-out mice with deficiencies in
      either CD4+ or CD8+ T cell-mediated immunity. To address the role of the class I-
      and class II-mediated pathways of T cell activation in contact hypersensitivity
      responses in mice with an intact immune system, we utilized various
      trinitrophenyl-derivatized peptides, which bind specifically with H-2Kb (major
      histocompatibility complex class I) or H-2I-Ab (major histocompatibility complex
      class II). The subcutaneous injection of major histocompatibility complex class
      II-specific, but not of class I-binding, hapten-derivatized peptides in
      incomplete Freund's adjuvant induced specific, albeit low, contact
      hypersensitivity responsiveness to trinitrochlorobenzene. When bone-marrow
      derived dendritic cells, however, were pulsed with the same peptides and
      administered intradermally, the opposite result was observed, namely that the
      class I binding peptides induced contact hypersensitivity responses similar to
      that observed after epicutaneous trinitrochlorobenzene application. In contrast,
      dendritic cells pulsed with major histocompatibility complex class II binding
      peptides did not reproducibly sensitize for contact hypersensitivity responses.
      Surprisingly, both immunization protocols efficiently induced CD8+ effector T
      cells. These results support the notion that CD8+ T cells are the dominant
      effector population mediating contact hypersensitivity responsiveness and that
      the CD4+ T cell subset only contributes little if at all.

PMID- 10951245
TI  - Evidence for involvement of the epidermal platelet-activating factor receptor in
      ultraviolet-B-radiation-induced interleukin-8 production.
AB  - Ultraviolet B radiation has been shown to generate cutaneous inflammation in part
      through inducing oxidative stress and cytokine production in human keratinocytes.
      Amongst the proinflammatory cytokines synthesized in response to ultraviolet B
      radiation is the potent chemoattractant interleukin-8. Though the lipid mediator
      platelet-activating factor (PAF) is synthesized in response to oxidative stress,
      and keratinocytes express PAF receptors linked to cytokine biosynthesis, it is
      not known whether PAF is involved in ultraviolet-B-induced epidermal cell
      cytokine production. These studies examined the role of the PAF system in
      ultraviolet-B-induced epidermal cell interleukin-8 biosynthesis using a novel
      model system created by retroviral-mediated transduction of the PAF-receptor
      negative human epidermal cell line KB with the human PAF receptor. Treatment of
      PAF-receptor-expressing KB cells with the metabolically stable PAF receptor
      agonist carbamoyl-PAF resulted in increased interleukin-8 mRNA and protein,
      indicating that activation of the epidermal PAF receptor was linked to
      interleukin-8 production. Ultraviolet B irradiation of PAF-receptor-expressing KB
      cells resulted in significant increases in both interleukin-8 mRNA and protein in
      comparison to ultraviolet-B-treated control KB cells. Pretreatment with PAF
      receptor antagonists inhibited both carbamoyl-PAF-induced and ultraviolet-B
      induced interleukin-8 production in the PAF-receptor-positive cells, but not in
      control KB cells. Similarly, treatment of the PAF-receptor-expressing primary
      cultures of human keratinocytes or the human epidermal cell line A-431 with
      carbamoyl-PAF or ultraviolet B radiation resulted in interleukin-8 production
      that was partially inhibited by PAF receptor antagonists. These studies suggest
      that the epidermal PAF receptor may be a pharmacologic target for ultraviolet B
      radiation in skin and thus may act to augment ultraviolet-B-mediated production
      of cytokines such as interleukin-8.

PMID- 10951246
TI  - High incidence and regression rates of solar keratoses in a queensland community.
AB  - The presence of solar keratoses on the skin is one of the major risk factors for
      basal cell and squamous cell carcinomas, which constitute a growing public health
      problem in today's white populations. In spite of this, little is known of the
      natural history of solar keratoses. We conducted follow-up studies to monitor the
      incidence, regression, and recurrence rates of solar keratoses in a random sample
      (N = 96) of the Nambour community in Queensland. At baseline, 43 participants
      (46%) were diagnosed with at least one solar keratosis [26 men (55%), 17 women
      (37%)] with a total count of 494 prevalent solar keratoses. The distribution of
      lesions per person was highly skewed, with 11 individuals (12%) having 65% of the
      total number of solar keratoses. During 12 mo of follow-up, 614 incident solar
      keratoses were diagnosed (549 in men and 65 in women); 526 solar keratoses
      regressed and 53 prevalent solar keratoses recurred, giving a net 45% increase in
      solar keratosis numbers in men (from 354 to 512 solar keratoses) and a net 44%
      reduction in women (from 114 to 64). Regression rates were higher in prevalent
      (74%) than incident (29%) solar keratoses. Solar keratosis prevalence increased
      with age in both sexes, and individuals with solar keratoses at baseline were
      over seven times more likely to develop additional solar keratoses in the next 12
      mo than those without prevalent solar keratoses at baseline. These results show
      that the natural history of solar keratoses in the community is one of high
      turnover and that a small percentage of susceptible individuals carry the major
      burden of solar keratoses in the community.

PMID- 10951247
TI  - Differential expression of connexins during stratification of human
      keratinocytes.
AB  - To assess whether gap junctions and connexins change during keratinocyte
      differentiation, we have studied epidermal equivalents obtained in organotypic
      cultures of keratinocytes from the outer root sheath of human hair follicles.
      These reconstituted tissues exhibit a number of differentiation and proliferation
      markers of human epidermis, including gap junctions, connexins, and K6 and Ki67
      proteins. Immunostaining and northern blots showed that gap junctions of the
      epidermal equivalents were made of Cx26 and Cx43. Cx26 was expressed in all
      keratinocyte layers, throughout the development of the epidermal equivalents. In
      contrast, Cx43 was initially observed only in the basal layer of keratinocytes
      and became detectable in the stratum spinosum and granulosum only after the
      epidermal equivalents had thickened. The levels of Cx26 and its transcript
      markedly increased as a function of stratification of the epidermal equivalents,
      whereas those of Cx43 remained almost constant. Microinjection of Lucifer Yellow
      into individual keratinocytes showed that gap junctions were similarly permeable
      at all stages of development of the epidermal equivalents. The data show that
      epidermal equivalents (i) feature a pattern of connexins typical of an actively
      renewing human interfollicular epidermis, and (ii) provide a model that
      reproduces the tridimensional organization of intact epidermis and that is
      amenable for experimentally testing the function of junctional communication
      between human keratinocytes.

PMID- 10951248
TI  - Transforming growth factor beta1 induces apoptosis in normal melanocytes but not
      in nevus cells grown in type I collagen gel.
AB  - We used type I collagen gel cultures to compare the growth requirements of
      melanocytes and dermal nevus cells. Melanocytes but not nevus cells undergo
      apoptosis in collagen unless supplied with growth stimulators such as fibroblast
      growth factor 2. To characterize the mechanism of melanocyte apoptosis in
      collagen, we tested the effects of transforming growth factor beta1, known to be
      functionally active in the skin. When picomolar amounts of transforming growth
      factor beta1 were added to normal melanocytes grown in type I collagen gel, their
      apoptosis was dramatically accelerated. In contrast, the apoptotic rate of nevus
      cells and melanoma cells grown under similar conditions was not affected by
      transforming growth factor beta1. The increased apoptosis of normal melanocytes
      was effectively counteracted by addition of either neutralizing transforming
      growth factor beta1 antibodies or fibroblast growth factor 2 to the collagen gel.
      Interestingly, the background apoptosis of normal melanocytes was also inhibited
      by transforming growth factor beta1 antibodies. By Western blotting we detected
      transforming growth factor beta-like immunoreactivity in melanocyte, nevus cell,
      and melanoma cell lysates. A sensitive bioassay confirmed that their medium
      contained considerable amounts of heat-activatable growth inhibitory activity
      that could partly be neutralized by transforming growth factor beta1 antibodies.
      It is evident that apoptosis of melanocytes grown in type I collagen gel can be
      mediated by both endogenous and exogenous transforming growth factor beta. We
      suggest that the balance between inhibitory growth factors such as transforming
      growth factor beta and stimulatory growth factors like fibroblast growth factor 2
      has the potential to regulate the growth, localization, and survival of normal
      melanocytes also in vivo. The resistance of nevus cells to transforming-growth
      factor-beta-mediated apoptosis may facilitate their ability to grow in the dermal
      compartment of the skin.

PMID- 10951249
TI  - Cytokine release and cytotoxicity in human keratinocytes and fibroblasts induced
      by phenols and sodium dodecyl sulfate.
AB  - Phenolic compounds used in pharmaceutical and industrial products can cause
      irritant contact dermatitis. We studied the effects of resorcinol, phenol, 3,5
      xylenol, chloroxylenol, and 4-hexyl-resorcinol on normal human epidermal
      keratinocytes and dermal fibroblasts for cytotoxicity and cytokine release,
      determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      methodology and enzyme-linked immunosorbent assay, respectively. An inverse
      correlation between phenol concentrations causing a 50% reduction in keratinocyte
      and fibroblast viability at 24 h and their octanol water-partition coefficients
      (i.e., hydrophobicity) was observed. 3,5-xylenol, chloroxylenol, hexyl
      resorcinol, and sodium dodecyl sulfate, but not resorcinol or phenol, induced
      release of interleukin-1alpha from keratinocytes at cytotoxic concentrations.
      Variable release of tumor necrosis factor-alpha and interleukin-8 from
      keratinocytes occurred only at toxic threshold concentrations of the phenols or
      sodium dodecyl sulfate. Subtoxic concentrations of phenols or sodium dodecyl
      sulfate did not induce cytokine release from keratinocytes. Neither the phenols
      nor sodium dodecyl sulfate induced release of the chemokines interleukin-8,
      growth-related oncogene-alpha or monocyte chemotactic protein-1 from fibroblasts.
      Conditioned media from keratinocytes treated with cytotoxic concentrations of 3,5
      xylenol, chloroxylenol, hexyl-resorcinol, or sodium dodecyl sulfate stimulated
      further release of the chemokines from fibroblasts above that obtained with
      control media. Rabbit anti-interleukin-1alpha serum inhibited keratinocyte
      conditioned media induction of chemokine release. We have shown a structure
      cytotoxicity relationship for a series of phenols as well as an association of
      interleukin-1alpha release with a cytotoxic effect. We demonstrated a cytokine
      cascade amplification step by the actions of stimulated keratinocyte media on
      cultured dermal fibroblasts, identifying interleukin-1alpha as the principal
      initiator of chemokine synthesis.

PMID- 10951250
TI  - Expression of cutaneous lymphocyte-associated antigen regulated by a set of
      glycosyltransferases in human T cells: involvement of alpha1, 3
      fucosyltransferase VII and beta1,4-galactosyltransferase I.
AB  - Cutaneous lymphocyte-associated antigen (CLA), which plays a key part in skin
      homing of human CD4+ memory T cells via CLA/E-selectin binding, is upregulated by
      IL-12 and downregulated by IL-4. Although alpha1,3-fucosyltransferase VII is
      essential for synthesis of the CLA carbohydrate epitope, little is known about
      how the CLA expression is regulated by a number of glycosyltransferases. A 6 wk
      long-term culture for the in vitro differentiation of naive Th cells to memory
      Th1 cells was employed. By repeated activation in the presence of IL-12, naive T
      cells differentiated into memory Th1 cells, resulting in the upregulation of CLA
      expression. The switching of cytokine from IL-12 to IL-4 at three cycles resulted
      in a marked downregulation of CLA. The transcript levels of 16
      glycosyltransferases and P-selectin glycoprotein ligand-1, all considered to be
      potentially involved in CLA synthesis, were determined after each cycle. The
      level of CLA expression was well correlated with the amounts of alpha1,3
      fucosyltransferase VII and beta1,4-galactosyltransferase I. Both were upregulated
      by IL-12 and downregulated by IL-4. In particular, alpha1,3-fucosyltransferase
      VII levels decreased markedly in the presence of IL-4. P-selectin glycoprotein
      ligand-1 and Core 2 beta1, 6-N-acetylglucosaminyltransferase were progressively
      up-regulated by repeated IL-12 stimulation, but they were not downregulated by IL
      4. The transcript levels of some genes examined were constitutive without any
      correlation to CLA expression. These results suggest that the level of CLA
      expression is determined by alpha1, 3-fucosyltransferase VII and beta1,4
      galactosyltransferase I, the other enzymes merely participating in the synthesis
      of CLA. In peripheral blood mononuclear cells, IL-12 and IL-4 profoundly
      upregulated and downregulated the alpha1,3-fucosyltransferase VII transcripts,
      respectively, but not the beta1,4-galactosyltransferase I ones, within only 2 h
      of in vitro culture. This suggested that alpha1,3-fucosyltransferase VII is
      transcriptionally regulated directly by IL-12 and IL-4.

PMID- 10951251
TI  - Mutation report: complete paternal uniparental isodisomy of chromosome 1: a novel
      mechanism for Herlitz junctional epidermolysis bullosa.
AB  - Uniparental disomy denotes a situation when an individual has inherited two
      copies of a specific chromosome from a single parent. Uniparental disomy has been
      demonstrated to be involved in the pathogenesis of recessively inherited diseases
      in rare cases. Here we report a patient of Japanese origin with Herlitz
      junctional epidermolysis bullosa (OMIM no. 226700), who died at the age of 8 mo
      from complications of the disease. The mutation analysis revealed that the
      proband was homozygous for a nonsense mutation C553X in the LAMC2 gene encoding
      the gamma2 chain of laminin 5. The father was a heterozygous carrier of this
      mutation whereas the mother had two normal alleles of this gene. The patient
      showed homozygosity for 15 known intragenic polymorphisms in the LAMC2 gene.
      Furthermore, genotype analysis, performed from the parents and the proband, using
      16 microsatellite markers spanning the entire chromosome 1, revealed that the
      patient was homozygous for all markers tested, and that these alleles originated
      from the father. Among the 16 markers, eight were fully informative for the
      absence of the maternal chromosome 1 in the proband, suggesting that the patient
      had complete paternal isodisomy of this chromosome. Thus, the Herlitz junctional
      epidermolysis bullosa phenotype in this patient is caused by homozygous LAMC2
      mutation C553X that is of paternal origin and results from nondisjunction and
      uniparental disomy involving monosomy rescue. This is a novel mechanism resulting
      in Herlitz junctional epidermolysis bullosa and has implications for assessment
      of the risk in subsequent pregnancies.

PMID- 10951252
TI  - Compound heterozygosity for a point mutation and a deletion located at splice
      acceptor sites in the LAMB3 gene leads to generalized atrophic benign
      epidermolysis bullosa.
AB  - An autosomal recessive disorder, generalized atrophic benign epidermolysis
      bullosa, is a rare form of nonlethal type junctional epidermolysis bullosa. It is
      associated not only with skin fragility but also with other unique clinical
      features including widespread atrophic skin changes, alopecia, reduced axillary
      and pubic hair, dysplastic teeth, and dystrophic nails. The majority of
      generalized atrophic benign epidermolysis bullosa cases are caused by mutations
      in the COL17A1 gene coding for type XVII collagen (or the 180 kDa bullous
      pemphigoid antigen). Another candidate gene for mutations in some forms of
      generalized atrophic benign epidermolysis bullosa is LAMB3 encoding the beta3
      chain of laminin 5. This report documents compound heterozygosity for novel
      mutations in LAMB3 of a Japanese patient showing typical clinical features of
      generalized atrophic benign epidermolysis bullosa. One is an A-to-G transversion
      at the splice acceptor site of intron 14, which is designated as a 1977-2A-->G
      mutation; the other is a deletion of 94 bp located at the junction of intron 18
      and exon 19, which is a 2702-29del94 mutation. Reverse transcriptase polymerase
      chain reaction analysis suggested skipping of exon 19 in LAMB3 mRNA produced from
      the allele with 2702-29del94 and impaired stability of the aberrant mRNA
      transcribed from the second allele with the 1977-2A-->G mutation.

PMID- 10951253
TI  - Communications: high dermal mast cell prevalence is a predisposing factor for
      basal cell carcinoma in humans.
AB  - Ultraviolet B radiation (280-320 nm) can initiate skin cancer as well as suppress
      the immune system, thereby preventing the rejection of ultraviolet-B-induced
      tumors. Recently we reported that there was not only a correlation but also a
      functional link between dermal mast cell prevalence and susceptibility to
      ultraviolet-B-induced systemic immunosuppression in multiple strains of mice. In
      this study, we investigated whether increased dermal mast cell prevalence is a
      significant predisposing factor for basal cell carcinoma development in humans.
      In 21 Danes with a history of basal cell carcinoma and 20 control subjects of
      similar age, sex, skin phototype, and recreational sun exposure over the past 12
      mo, dermal mast cell prevalence was quantified on non-sun-exposed buttock skin.
      We investigated this skin site in order to avoid any changes in mast cell
      prevalence caused by sun exposure and assumed that the prevalence of mast cells
      in buttock skin correlated with that at sun-exposed sites at critical times in
      the development of basal cell carcinomas. Patients with a history of basal cell
      carcinoma had a significantly higher median dermal mast cell prevalence than
      control subjects (p = 0.01, Mann-Whitney U ). No correlation was observed between
      dermal mast cell prevalence and age of basal cell carcinoma patients and control
      subjects. These results suggest that increased dermal mast cell prevalence is a
      predisposing factor for basal cell carcinoma development in humans. We
      hypothesize that mast cells function in humans, as in mice, by initiating
      immunosuppression and thereby allowing a permissive environment for basal cell
      carcinoma development.

PMID- 10951254
TI  - 13-cis retinoic acid exerts its specific activity on human sebocytes through
      selective intracellular isomerization to all-trans retinoic acid and binding to
      retinoid acid receptors.
AB  - Despite its potent biologic effect on human sebocytes, 13-cis retinoic acid
      exhibits low binding affinity for cellular retinoic acid binding proteins and
      nuclear retinoid receptors. Hence, 13-cis retinoic acid may represent a pro-drug
      possibly acting through all-trans isomerization. In this study, marked
      isomerization of 13-cis retinoic acid has been confirmed in cultured SZ95
      sebocytes showing 2- to 15-fold higher levels of all-trans retinoic acid at 12-72
      h, as measured by high performance liquid chromatography. In contrast, only low
      amounts of all-trans retinoic acid were converted intracellularly to its 13-cis
      isoform. 9-cis retinoic acid was not detected after either 13-cis retinoic acid
      or all-trans retinoic acid treatment. The rapid isomerization of 13-cis retinoic
      acid to high levels of all-trans retinoic acid was a sebocyte-specific event, as
      no significant isomerization of 13-cis retinoic acid to all-trans retinoic acid
      occurred in HaCaT keratinocytes. De novo mRNA expression of cytochrome P450 1A1,
      a major xenobiotic metabolizing enzyme, in SZ95 sebocytes was induced by all
      trans retinoic acid, but not by 13-cis retinoic acid. In addition, mRNA levels of
      cellular retinoic acid-binding protein II, which is supposed to regulate the
      concentration of intracellular all-trans retinoic acid, rapidly increased under
      all-trans retinoic acid treatment (30 min-6 h), whereas the 13-cis retinoic acid
      effect was markedly weaker and delayed. Both 13-cis retinoic acid and all-trans
      retinoic acid suppressed mRNA expression of cytochrome P450 1A2. In parallel
      experiments, 13-cis retinoic acid significantly reduced SZ95 sebocyte
      proliferation at 10-7 M, show- ing 30-40% inhibition after 9 d. All-trans
      retinoic acid and 9-cis retinoic acid exhibited similar anti-proliferative
      effects. AGN 193109, a pan-antagonist of the retinoic acid receptors, antagonized
      the anti-proliferative activity of all retinoic acid isomers tested in a
      concentration-dependent manner with complete abolishment at ratios of 1:10 13-cis
      retinoic acid and 1:1 all-trans retinoic acid. Coincubation of SZ95 sebocytes
      with 13-cis retinoic acid and AGN 193109 did not alter the intracellular
      concentration of 13-cis retinoic acid and its isomerization profile. In contrast,
      the retinoid X receptor antagonist CD 3507 did not affect the inhibition of SZ95
      sebocyte proliferation induced by retinoic acids. Our findings indicate: (i) a
      selective 13-cis retinoic acid isomerization to all-trans retinoic acid in the
      intracellular compartment of SZ95 sebocytes; (ii) a reduced all-trans retinoic
      acid inactivation process after 13-cis retinoic acid treatment as compared with
      treatment with all-trans retinoic acid; and (iii) a retinoic acid receptor
      mediated inhibition of SZ95 sebocyte proliferation. These data explain the
      sebocyte-specific activity of 13-cis retinoic acid and support a pro-drug/drug
      relation between 13-cis retinoic acid and all-trans retinoic acid.

PMID- 10951255
TI  - Letters to the editor: identification of polymorphic variants of the GLI1
      oncogene.

PMID- 10951256
TI  - A novel arginine-->Serine mutation in EDA1 in a Japanese family with X-linked
      anhidrotic ectodermal dysplasia.

PMID- 10951257
TI  - Abstracts: mutations in the MRP6 gene cause pseudoxanthoma elasticum

PMID- 10951259
TI  - Pathogenesis in pemphigus vulgaris: A central role for the armadillo protein
      plakoglobin

PMID- 10951258
TI  - Collagen 17A1 gene correction using spliceosome mediated RNA trans-splicing
      (SMaRTtrade mark) technology

PMID- 10951260
TI  - Microphthalmia and loss of coat pigmentation from transgenic expression of a
      neurogenic factor in pigment cell precursors

PMID- 10951261
TI  - Cloning and initial characterization of human epsin 3, a novel matrix-induced
      keratinocyte specific transcript

PMID- 10951262
TI  - Comparative analysis of the global transcriptional profile of human skin-homing
      memory T lymphocytes vs. non-skin homing memory and naive T lymphocytes

PMID- 10951263
TI  - Gangliosides block keratinocyte binding to fibronectin through carbohydrate
      carbohydrate binding to the alpha5 subunit of alpha5beta1

PMID- 10951265
TI  - Intravenous administration of RNA suppresses the induction of delayed-type
      hypersensitivity (DTH) to tumor-associated antigens

PMID- 10951264
TI  - Anti-CD11a treatment for psoriasis concurrently increases circulating T-cells and
      decreases plaque T-cells, consistent with inhibition of cutaneous T-cell
      trafficking

PMID- 10951266
TI  - Matrix metalloproteinases in human melanoma.
AB  - Cutaneous melanoma is a highly invasive and metastatic tumor. Degradation of
      basement membranes and extracellular matrix is an essential step in melanoma cell
      migration, invasion, and metastasis formation. Matrix metalloproteinases and
      their tissue inhibitors play a crucial role in these complex multistep processes.
      Melanoma cells may express a number of matrix metalloproteinase family members
      (MMP-1, MMP-2, MMP-9, MMP-13, and MT1-MMP) as well as their tissue inhibitors
      (TIMP-1, TIMP-2, and TIMP-3). Numerous studies have examined matrix
      metalloproteinases, their tissue inhibitors, and the molecules that regulate
      their expression and/or activation in melanoma cell lines in vitro and in vivo,
      and in human melanocytic lesions. Recent results have indicated that adhesion
      molecules such as CD44 and integrin alphavbeta3 are involved in positioning
      activated matrix metalloproteinase molecules on the cell surface of invasive
      tumor cells. In this review we evaluate these novel aspects of the role of matrix
      metalloproteinases and their tissue inhibitors in melanoma progression. We
      conclude that the balance between levels of activated matrix metalloproteinases
      and expression levels of their tissue inhibitors, and the coexpression of
      activated matrix metalloproteinases and adhesion molecules are important factors
      in determining melanoma cell invasion, tumor growth, and metastasis formation.

PMID- 10951267
TI  - Histidine decarboxylase expression in human melanoma.
AB  - Histamine has been implicated as one of the mediators involved in regulation of
      proliferation in both normal and neoplastic tissues. Histidine decarboxylase, the
      only enzyme that catalyzes the formation of histamine from L-histidine, is an
      essential regulator of histamine levels. In this study, we investigated the gene
      and protein expression of histidine decarboxylase in melanoma. Reverse
      transcriptase polymerase chain reaction and in situ hybridization studies of WM
      35, WM-983/B, HT-168, and M1 human melanoma cell lines both resulted in positive
      signals for histidine decarboxylase messenger RNA. A polyclonal chicken antibody
      was developed against human histidine decarboxylase and protein expression was
      confirmed by western blot analysis of the cell lysates, revealing a predominant
      immunoreactive band at approximately 54 kDa corresponding to monomeric histidine
      decarboxylase. Protein expression of histidine decarboxylase was also shown by
      flow cytometric analysis and strong punctate cytoplasmic staining of melanoma
      cell lines. Moreover, both primary and metastatic human melanoma tissues were
      brightly stained for histidine decarboxylase. When compared with the very weak or
      no reactions on cultivated human melanocytes both western blot and
      immunohistochemical studies showed much stronger histidine decarboxylase
      expression in melanoma cells. These findings suggest that expression of histidine
      decarboxylase is elevated in human melanoma.

PMID- 10951268
TI  - Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo.
AB  - Our recent studies have demonstrated that PPARalpha activators stimulate
      differentiation and inhibit proliferation in cultured human keratinocytes and
      accelerate epidermal development and permeability barrier formation in fetal rat
      skin explants. As the role of PPARalpha activation in adult epidermis is not
      known, the aim of this study was to determine if topically applied PPARalpha
      ligands regulate keratinocyte differentiation in murine epidermis. Topical
      treatment with PPARalpha activators resulted in decreased epidermal thickness.
      Expression of structural proteins of the upper spinous/granular layers
      (involucrin, profilaggrin-filaggrin, loricrin) increased following topical
      treatment with PPARalpha activators. Furthermore, topically applied PPARalpha
      activators also increased apoptosis, decreased cell proliferation, and
      accelerated recovery of barrier function following acute barrier abrogation.
      Experiments with PPARalpha-/- knockout mice showed that these effects are
      specifically mediated via PPARalpha. Compared with the epidermis of PPARalpha+/+
      mice, involucrin, profilaggrin-filaggrin, and loricrin expression were slightly
      decreased in PPARalpha-/- mice. Moreover, topical clofibrate treatment did not
      increase epidermal differentiation in PPARalpha-/- mice. Furthermore, in cultured
      human keratinocytes we have demonstrated that PPARalpha activators induce an
      increase in involucrin mRNA levels. We have also shown that this increase in gene
      expression requires an intact AP-1 response element at -2117 to -2111 bp. Thus,
      stimulation of PPARalpha stimulates keratinocyte/epidermal differentiation and
      inhibits proliferation.

PMID- 10951269
TI  - Keratinocyte differentiation in hyperproliferative epidermis: topical application
      of PPARalpha activators restores tissue homeostasis.
AB  - We recently showed that topically applied PPARalpha activators promote epidermal
      differentiation in intact adult mouse skin. In this study we determined the
      effect of clofibrate and Wy-14,643, activators of PPARalpha, on
      hyperproliferative epidermis in hairless mice, induced either by repeated barrier
      abrogation (subacute model) or by essential fatty acid deficiency (chronic
      model). The hyperproliferative epidermis was characterized by an increased number
      of proliferating cells expressing proliferating cell nuclear antigen. Topical
      treatment with PPARalpha activators resulted in a substantial decrease in
      epidermal hyperplasia in both the subacute and chronic models of
      hyperproliferation. Following topical treatment, proliferating cell nuclear
      antigen-expressing cells were restricted to the basal layer, similar to normal
      epidermis. In hyperproliferative epidermis there was decreased expression of
      involucrin, profilaggrin-filaggrin, and loricrin as assayed by in situ
      hybridization and immunohistochemistry. Following topical treatment with PPAR
      activators staining for these mRNAs and proteins increased towards normal levels.
      Finally, topically applied clofibrate also increased apoptosis. This study
      demonstrates that topical PPAR activators have profound effects on epidermal gene
      expression in hyperproliferative skin disorders. Treatment with PPARalpha
      activators normalizes cell proliferation and promotes epidermal differentiation,
      correcting the cutaneous pathology. This study identifies PPARalpha activators as
      potential skin therapeutic agents.

PMID- 10951270
TI  - Genomic amplification of the human plakophilin 1 gene and detection of a new
      mutation in ectodermal dysplasia/skin fragility syndrome.
AB  - Ectodermal dysplasia/skin fragility syndrome is a recently described autosomal
      recessive disease affecting skin, nails, and hair (MIM 604536), that results from
      mutations in plakophilin 1, a structural component of desmosomes. We report a new
      plakophilin 1 mutation in an affected patient as well as detailing the intron
      exon organization of the gene to facilitate future polymerase chain reaction
      based mutation screening. Using polymerase chain reaction amplification of
      genomic DNA, we identified 15 exons spanning approximately 50 kb. Direct
      sequencing disclosed several nonpathogenic intragenic polymorphisms, as well as a
      homozygous splice site mutation (1233-2 A-->T; GenBank Z73678) in a 17 y old
      affected male. The clinical features comprised skin erosions, dystrophic nails,
      sparse hair, and painful thickening and cracking of palms and soles. Skin biopsy
      showed negative immunolabeling with an anti-plakophilin 1 antibody and small
      desmosomes. These results expand the database of plakophilin 1 mutations and
      demonstrate the importance of this protein in the stabilization of desmosomal
      adhesion in terminally differentiating keratinocytes.

PMID- 10951271
TI  - The membrane-associated protein pKe#192/MAP17 in human keratinocytes.
AB  - In order to isolate genes that are upregulated in human keratinocytes upon loss
      of cell/matrix contact, a subtractive cDNA library was constructed from dispase
      treated versus untreated keratinocytes. Among the cloned cDNAs one was pKe#192
      having an open reading frame of 411 bp. By database analysis pKe#192 was found to
      be identical with the gene "MAP17" previously isolated from human kidney. Kyte
      Doolittle hydrophobicity analyzes showed a hydrophobic amino terminus of 13 amino
      acids, a transmembrane region and a 61 amino acid hydrophilic carboxy-terminus
      and two potential phosphorylation sites. In order to study regulation of
      pKe#192/MAP17 expression, RNA was extracted from resting human keratinocytes and
      from keratinocytes stimulated by dispase-induced detachment from the growth
      substratum. Reverse transcription polymerase chain reaction did not reveal
      specific mRNA in resting keratinocytes, whereas mRNA was detectable after
      detachment. For further characterization poly- and monoclonal antibodies were
      generated against a recombinant fusion protein. Immunohistologic studies using
      the mono- and polyclonal antibodies showed staining of the upper layers of the
      stratum granulosum in normal human epidermis. The staining was colocalized with
      involucrin. Immunhistologic staining of frozen sections derived from lesional
      skin of bullous pemphigoid und pemphigus vulgaris indicated that pKe#192/MAP17
      was upregulated in the epidermis adjacent to the blister. Taken together, the
      data demonstrate that pKe#192/MAP17 is expressed in keratinocytes and may be
      involved in epidermal physiology and pathology. KEYWORDS: bullous
      diseases/differentiation.

PMID- 10951272
TI  - Neprilysin, a novel target for ultraviolet B regulation of melanogenesis via
      melanocortins.
AB  - Compelling evidence suggest a role for melanocortins in the regulation of
      melanogenesis by ultraviolet radiation. Within the epidermis, melanocytes and
      keratinocytes produce alpha-melanocyte-stimulating hormone and
      adrenocorticotropic hormone. The persistence and the strength of the biologic
      signal delivered by these peptides depend on their local concentration, which is
      controlled by the rate of peptide production and by the rate of its degradation.
      In this study, we investigated the mechanism of melanocortin degradation by
      melanocytes and the effect of ultraviolet on this process. We have focused our
      attention on a neutral endopeptidase, neprilysin, which has been implicated in
      the ending of numerous peptidergic signals. We have shown that this enzyme is
      expressed at the surface of human melanocytes. Interestingly, its activity and
      its expression are dramatically downregulated by ultraviolet B treatment.
      Moreover, in the presence of phosphoramidon, a stable inhibitor of neprilysin, we
      observed an increased efficiency of alpha-melanocyte-stimulating hormone and
      adrenocorticotropic hormone to stimulate both tyrosinase activity and
      microphthalmia expression. Taken together, these data indicate that neprilysin
      expressed by melanocytes has a physiologic role in the regulation of
      melanogenesis by proopiomelanocortin peptide. Further, its downregulation by
      ultraviolet B irradiation shed light on a new and appealing mechanism of
      ultraviolet B induced melanogenesis via the control of melanocortins degradation.

PMID- 10951273
TI  - Placenta growth factor is induced in human keratinocytes during wound healing.
AB  - Placenta growth factor (PlGF) is a dimeric glycoprotein, structurally and
      functionally related to the vascular endothelial growth factor, a potent
      angiogenic/permeability factor known to play a role in the neoangiogenesis during
      wound repair. In this study we evaluated the expression of PlGF in human
      keratinocytes and investigated its possible role in wound healing. Northern blot
      analysis on cultured keratinocytes revealed a 1.7 kb mRNA transcript and reverse
      transcriptase-polymerase chain reaction allowed the detection of two PlGF
      isoforms generated by alternative RNA splicing. PlGF and vascular endothelial
      growth factor homodimers as well as vascular endothelial growth factor/PlGF
      heterodimers could be detected in keratinocyte conditioned medium. Increased
      expression of both PlGF mRNA and protein was observed upon treatment of
      keratinocytes with epidermal growth factor, transforming growth factor-alpha,
      transforming growth factor-beta, and interleukin-6, all cytokines present at the
      wound site during the early phase of repair. The analysis of human full-thickness
      healing wounds revealed appreciable levels of PlGF mRNA and protein in the
      migrating keratinocytes starting from day 3 after injury, and increasing at day
      5. At day 7 PlGF mRNA was no longer detectable, while the protein was still
      expressed by migrating suprabasal keratinocytes. At day 13, when the wound had
      reepithelialized, PlGF immunostaining was completely negative. By in situ
      hybridization an intense signal for PlGF was also found on endothelial
      capillaries adjacent to the wound. These data demonstrate that keratinocytes are
      a source of PlGF during wound healing in vivo and indicate a role for this factor
      in the neoangiogenesis process associated with cutaneous wound repair.

PMID- 10951274
TI  - Erythroplasia of queyrat: coinfection with cutaneous carcinogenic human
      papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ.
AB  - Erythroplasia of Queyrat is a carcinoma in situ that mainly occurs on the glans
      penis, the prepuce, or the urethral meatus of elderly males. Up to 30% progress
      to squamous cell carcinoma. The cause of erythroplasia of Queyrat is largely
      unknown. Human papillomavirus type 16 DNA has previously been detected only in
      very few distinctly characterized patients. We have investigated 12 paraffin
      embedded biopsies from eight patients with penile erythroplasia of Queyrat and
      control biopsies of inflammatory penile lesions, of genital Bowen's disease, and
      of premalignant/malignant cervical or vulvar lesions by 10 different polymerase
      chain reaction protocols for the presence of cutaneous and genital/mucosal human
      papillomaviruses. Human papillomavirus typing was performed by sequencing
      (cloned) polymerase chain reaction products. Human papillomavirus DNA was
      detected in all erythroplasia of Queyrat patients and in none of the controls
      with inflammatory penile lesions. The rare cutaneous carcinogenic
      epidermodysplasia verruciformis-associated human papillomavirus type 8 was
      present in all erythroplasia of Queyrat patients and the genital high-risk human
      papillomavirus type 16 in seven of eight patients (88%). In addition to human
      papillomavirus type 8 and human papillomavirus type 16, four patients carried the
      genital carcinogenic human papillomavirus type 39 and/or type 51. All human
      papillomavirus type 8 sequences found in erythroplasia of Queyrat showed some
      polymorphism among each other and differed in specific nucleotide exchanges from
      the human papillomavirus type 8 reference sequence. Viral load determinations
      (human papillomavirus copies/beta-globin gene copies) by realtime polymerase
      chain reactions showed that the human papillomavirus type 16 levels in the
      erythroplasia of Queyrat biopsies were one to five orders of magnitude higher
      than the human papillomavirus type 8 levels. Human papillomavirus type 8 was not
      detected in cervical or vulvar precancerous and cancerous lesions and in Bowen's
      disease lesions that carried genital human papillomavirus types. The data suggest
      that in erythroplasia of Queyrat, in contrast to other genital neoplasias, a
      coinfection with human papillomavirus type 8 and carcinogenic genital human
      papillomavirus types occurs. The presence or absence of human papillomavirus type
      8 might help to distinguish between penile erythroplasia of Queyrat and Bowen's
      diseases.

PMID- 10951275
TI  - mu-Crystallin, thyroid hormone-binding protein, is expressed abundantly in the
      murine inner root sheath cells.
AB  - In an attempt to investigate the genes expressed during the development of mouse
      hair follicles, we employed RNA differential display and identified a cDNA
      encoding micro-crystallin, that is a major component of kangaroo lens and a
      cytosolic NADP-regulated thyroid hormone-binding protein in human kidney. In
      northern blot study, mu-crystallin transcripts were detected in skin at the
      highest level among the mouse tissues, whereas lower but detectable in the eye,
      brain, kidney, heart, lung, and liver. Furthermore, in mouse skin, the gene
      expression of mu-crystallin followed hair cycle fundamentally, increased
      significantly during mid- and late anagen phases and decreased during the
      catagen, telogen, and early anagen phases. In situ hybridization revealed that mu
      crystallin gene starts to be activated in hair cone of anagen III, and that in
      anagen VI, its expression is detected predominantly in the cuticle layer of the
      inner root sheath from the upper hair bulb to the middle portion of the
      keratogenous zone and in the Huxley's layer through the keratogenous zone. The
      expression was not detected in catagen, telogen, and early anagen hair follicles,
      and any other skin components. These results suggest the possible involvement of
      mu-crystallin in the development of mouse hair follicles during the anagen phase.

PMID- 10951276
TI  - High-expression of sphingomyelin deacylase is an important determinant of
      ceramide deficiency leading to barrier disruption in atopic dermatitis.
AB  - We have previously demonstrated that there is abnormal expression of
      sphingomyelin (SM) deacylase-like enzyme in the epidermis of patients with atopic
      dermatitis (AD), which results in decreased levels of ceramides in their involved
      and uninvolved stratum corneum. For quantitation of the expression of SM
      deacylase in AD, we synthesized 16-(9-anthroyloxy)
      hexadecanoylsphingosylphosphorylcholine or [palmitic acid-14C] SM and used them
      as substrates to directly measure the activity of SM deacylase by detecting the
      release of labeled free fatty acid. Direct enzymatic measurements demonstrated
      that stratum corneum from lesional forearm skin (volar side) of AD patients has
      an extremely high SM deacylase activity that is at least five times higher than
      in the stratum corneum from healthy controls. In stratum corneum from nonlesional
      skin of AD patients, SM deacylase activity is still at least three times higher
      than in healthy controls. In contrast, stratum corneum from contact dermatitis
      patients shows levels of SM deacylase similar to healthy controls. In extracts of
      whole epidermis biopsies from AD patients, SM deacylase activities are
      significantly (3-fold) increased over healthy controls in the particulate
      fraction, whereas there is no significant difference in the activity of
      sphingomyelinase between AD and healthy control. In peripheral blood lymphocytes
      of AD patients, there is no increase in activity compared with healthy controls,
      indicating a possibility that the high expression of SM deacylase is highly
      associated with the skin of AD patients. These findings suggest that, in contrast
      to changes in sphingolipid metabolism due to aging, the hitherto undiscovered
      enzyme SM deacylase, is highly expressed in the epidermis of AD patients, and
      competes with sphingomyelinase or beta-glucocerebrosidase for the common
      substrate SM or glucosylceramide, which leads to the ceramide deficiency of the
      stratum corneum in AD.

PMID- 10951277
TI  - Evidence for the existence of a self-regulated enzymatic process within the human
      stratum corneum -an unexpected role for urocanic acid.
AB  - The existence of a flux of proton donors from skin (inner part of the forearm) to
      the electrode was observed in 12 male and female volunteers. This flux was used
      to collect and identify the ionic species responsible for skin acidity. It was
      then found that: (i) pK of these proton donors (pK = 6.13 +/- 0.07) was quasi
      identical to that of trans-urocanic acid (6.10), and (ii) the amount of urocanic
      acid present in stratum corneum was sufficient in itself to explain the acidic
      level as measured with pH meter (R = 0.8484, n = 10, p = 0.00136). As a result,
      the contribution of other ionic species can be considered as negligible in normal
      human skin. The data recorded led us to identify three groups (Fast, Medium, and
      Slow) characterized by different skin surface pH values (low, medium, and close
      to neutral) and showing a pH gradient in the outer layers of the stratum corneum,
      or not. Data analysis suggests that these characteristics depend on urocanic acid
      production rate within the stratum corneum and that this production rate is self
      regulated by its urocanic acid content.

PMID- 10951278
TI  - Broad-spectrum sunscreens offer protection against urocanic acid
      photoisomerization by artificial ultraviolet radiation in human skin.
AB  - Cis-urocanic acid (UCA) has been indicated as an important mediator of
      ultraviolet (UV)-induced immunosuppression. In this study we describe a rapid,
      noninvasive method for the determination of the protective capacity of various
      sunscreens against the UV-induced isomerization of trans-UCA into its cis form.
      For this purpose we applied sunscreens prior to in vivo exposure of human
      volunteers with single or repeated broadband UVB irradiations of 100 mJ per cm2.
      We found significant but different levels of protection against UCA
      photoisomerization by all sunscreens that correlated with the sun protection
      factor. A comparison of various sunscreens with a sun protection factor of 10,
      showed that the best protection was offered by the sunscreens (containing organic
      UV filters or TiO2) with broad absorption spectra. The ability to inhibit cis-UCA
      formation was not influenced by the penetration characteristics of sunscreens, as
      determined by application of the sunscreen on quartz glass that was placed on the
      skin, preventing penetration of sunscreen in the skin. In addition ex vivo UV
      exposure of human skin was employed to permit other tests of immunomodulation, in
      this case the mixed epidermal cell lymphocyte reaction. The advantage of this ex
      vivo method is that there is no need to take biopsies from volunteers. Ex vivo
      irradiation of human skin with a single dose of 200 mJ per cm2 resulted in
      similar protection by the sunscreens against cis-UCA formation as in the in vivo
      system. Furthermore, the mixed epidermal cell lymphocyte reaction data correlated
      with the cis-UCA findings. We conclude that UCA isomerization is an excellent
      method to determine sunscreen efficacy and that broad-spectrum sunscreens offer
      good immunoprotection.

PMID- 10951279
TI  - Ultraviolet B-mediated phosphorylation of the small heat shock protein HSP27 in
      human keratinocytes.
AB  - Exposure of human keratinocytes to environmental stress is known to induce
      changes in the expression, phosphorylation, and subcellular relocalization of the
      27 kDa heat shock protein. This study demonstrates that ultraviolet B (280-320
      nM) irradiation with physiologic doses induces a dose-dependent phosphorylation
      of 27 kDa heat shock protein, generating the more acidic 27 kDa heat shock
      protein B, C, and D isoforms. Ultraviolet B also induces perinuclear cytoplasmic
      relocation and nuclear translocation of 27 kDa heat shock protein and caused
      aggregation of cytoplasmic actin filaments into a broad perinuclear distribution.
      The ultraviolet B-induced phosphorylation is reversible, returning to baseline
      levels 4 h after exposure, and this coincides with the reversal of ultraviolet B
      induced actin reorganization. The ultraviolet B-induced phosphorylation is not
      affected by the protein kinase C inhibitor, GF 109203X, is partially inhibited by
      epidermal growth factor receptor tyrosine kinase inhibitor, PD 153035, and is
      substantially inhibited by the specific p38 mitogen-activated protein kinase
      inhibitor, SB 203580. In addition, pretreatment of cells with the anti-oxidant N
      acetyl cysteine partially inhibits ultraviolet B-and oxidant-induced 27 kDa heat
      shock protein phosphorylation. The p38 mitogen-activated protein kinase cascade
      is thus the major transduction pathway for ultraviolet B-induced 27 kDa heat
      shock protein phosphorylation, and reactive oxygen species generated in response
      to ultraviolet B also contribute to this phosphorylation. As 27 kDa heat shock
      protein phosphorylation and relocalization has been associated with increased
      cell survival after environmental insult, our data suggest that ultraviolet B, in
      addition to initiating recognized cytotoxic events in keratinocytes, also
      initiates a signaling pathway that may provide cellular protection against this
      ubiquitous environmental insult.

PMID- 10951280
TI  - Low doses of UVB or UVA induce chromosomal aberrations in cultured human skin
      cells.
AB  - Chromosomal defects are frequently present in malignant and premalignant skin
      disorders; however, it is not known whether ultraviolet radiation from sunlight
      plays a role in their induction. To obtain information on the ability of
      ultraviolet A and ultraviolet B to induce chromosomal aberrations, cultured
      melanocytes and fibroblasts were exposed to physiologic doses of ultraviolet A or
      ultraviolet B and, for comparison, to gamma rays. As a measure of chromosomal
      aberrations, the formation of micronuclei was determined. To obtain sufficient
      statistical data on induced micronuclei and cell kinetics, a flow cytometry
      method has been modified and applied. The flow cytometry method analysis is based
      on staining the DNA with ethidium bromide and the cell membranes with 1,6
      diphenyl-1,3,5,-hexatriene. We observed dose-dependent micronuclei formation
      after gamma or ultraviolet B irradiation in both cell types and also for
      ultraviolet A in fibroblasts. The yield of micronuclei induced in fibroblasts by
      ultraviolet A was only a factor 15 smaller than that induced by ultraviolet B
      (313 nm). The results indicate that 10 kJ per m2 (equivalent to 1 minimal
      erythema dose) of ultraviolet B and 150 kJ per m2 of ultraviolet A (0.2 minimal
      erythema dose) can induce 1% of micronuclei in fibroblasts, equivalent to the
      induction due to 0.6 Gy of gamma radiation. In conclusion, physiologic doses of
      sunlight can induce chromosomal aberrations at a level comparable with that
      observed after exposure to approximately 1 Gy of ionizing radiation. Therefore,
      sunlight can be considered a potential inducer of chromosomal aberrations in skin
      cells, which may contribute to skin carcinogenesis.

PMID- 10951281
TI  - Non-invasive raman spectroscopic detection of carotenoids in human skin.
AB  - Carotenoids are thought to play a significant part in the skin's anti-oxidant
      defense system, and may help prevent malignancy. Inability to measure skin
      carotenoid content readily has, however, made it difficult to establish the
      relationship between carotenoid concentration and the occurrence of cutaneous
      malignancy. We have measured in vivo carotenoid concentration using a noninvasive
      optical method, Raman spectroscopy. To validate our instrumentation,
      abdominoplasty skin was evaluated by both Raman spectroscopy and high-performance
      liquid chromatography determination for carotenoid content. Evaluation of the
      Raman signal in specific carotenoid solutions was also performed. Precision of
      Raman measurements within skin sites, within subjects, and between subjects was
      measured. Sensitivity of the method was evaluated as a function of anatomical
      region and the distribution of carotenoids within the stratum corneum. Lastly, we
      evaluated the Raman signal in actinic keratosis and basal cell carcinoma lesions
      and perilesional skin and compared this with region-matched sites in healthy
      subjects. Our results indicate that the Raman scattering method reflects the
      presence of carotenoids in human skin and is highly reproducible. Evaluation of
      five anatomical regions demonstrated significant differences in carotenoid
      concentration by body region with the highest carotenoid concentration noted in
      the palm. Comparison of carotenoid concentrations in basal cell carcinomas,
      actinic keratosis, and their perilesional skin demonstrate a significantly lower
      carotenoid concentration than in region-matched skin of healthy subjects. These
      results represent the first evidence that carotenoid concentration in the skin
      correlate with the presence or absence of skin cancer and precancerous lesions.

PMID- 10951282
TI  - Formation and kinetics of MHC class I-ovalbumin peptide complexes on immature and
      mature murine dendritic cells.
AB  - Dendritic cells (DC) are professional antigen-presenting cells that are able to
      induce primary T cell responses. Therefore, several strategies employ peptide
      pulsed DC in tumor immunotherapy. For efficient antigen presentation and
      induction of an immune response by DC the number and stability of MHC I-peptide
      complexes is crucial. We studied this issue by using the antibody 25-D1.16 that
      specifically detects OVA peptide SIINFEKL in conjunction with H-2 Kb molecules,
      and determined its kinetics on mature and immature bone marrow-derived murine DC.
      Optimal peptide loading was reached after 8-16 h at 50 microM peptide pulse, and
      was comparable in serum-free versus serum-containing medium. Stimulation of DC
      with LPS or Poly I:C, and to a lesser extent TNF-alpha, upregulated the total
      number of surface MHC I molecules and thus improved peptide loading. Pulse-chase
      experiments revealed a constant half-life of peptide/Kb complexes independent of
      preceding DC stimulation or their maturation stage. The duration of peptide/Kb
      complex expression on mature DC, however, could be extended from 24 h to 72 h
      when the cultures were pretreated with LPS or Poly I:C, but not TNF-alpha. These
      data might have important implications for the clinical application of peptide
      pulsed DC in tumor immunotherapy.

PMID- 10951283
TI  - Changes in tactile spatial discrimination and cutaneous coding properties by skin
      hydration in the elderly.
AB  - Neurosensory tactile functions were investigated in human subjects by two
      different and complementary experimental approaches. First, a conventional
      psychophysical method (two-point gap discrimination) was used to determine the
      tactile discrimination threshold by analyzing the subjects' ability to detect a
      gap of variable width between two contact points when a series of stimuli was
      applied to the skin. Using this method we confirmed the marked degradation of
      tactile spatial acuity with age and showed that skin discriminative function was
      partially restored after hydration of the skin with a moisturizer. The second
      approach consisted of a microneurographic recording of tactile afferent fibers in
      response to two types of mechanical stimuli applied reproducibly to the
      corresponding receptive fields. With this method, we found that the afferent
      messages were depressed following hydration of the skin surface. Thus, partial
      restoration of tactile spatial acuity after hydration appears to be due to both a
      softening of the stratum corneum permitting better localization of the stimulus
      and a weaker transfer of the stimulus toward the sensory receptors.

PMID- 10951284
TI  - Permeability barrier disorder in Niemann-Pick disease: sphingomyelin-ceramide
      processing required for normal barrier homeostasis.
AB  - Prior studies have established the requirement for enzymatic hydrolysis of
      glucosylceramides to ceramide for epidermal barrier homeostasis. In this study,
      we asked whether sphingomyelin-derived ceramide, resulting from acid
      sphingomyelinase activity, is also required for normal barrier function. We
      showed first, that a subset of Niemann-Pick patients with severe acid
      sphingomyelinase deficiency (i.e., <2% residual activity) demonstrate abnormal
      permeability barrier homeostasis, i.e., delayed recovery kinetics following acute
      barrier disruption by cellophane tape-stripping. To obtain further mechanistic
      insights into the potential requirement for sphingomyelin-to-ceramide processing
      for the barrier, we next studied the role of acid-sphingomyelinase in hairless
      mouse skin. Murine epidermis contains abundant acid-sphingomyelinase activity
      (optimal pH 5.1-5.6). Two hours following acute barrier disruption by tape
      stripping, acid-sphingomyelinase activity increases 1. 44-fold (p<0.008 versus
      vehicle-treated controls), an increase that is blocked by a single topical
      application of the acid-sphingomyelinase inhibitor, palmitoyldihydrosphingosine.
      Furthermore, both palmitoyldihydrosphingosine and desipramine, a chemically and
      mechanically unrelated acid-sphingomyelinase inhibitor, significantly delay
      barrier recovery both 2 and 4 h after acute barrier abrogation. Inhibitor
      application also causes both an increase in sphingomyelin content, and a
      reduction of normal extracellular lamellar membrane structures, in the stratum
      corneum. Both of the inhibitor-induced delays in barrier recovery can be
      overridden by co-applications of topical ceramide, demonstrating that an
      alteration of the ceramide-sphingomyelin ratio, rather than sphingomyelin
      accumulation, is likely responsible for the barrier abnormalities that occur with
      acid-sphingomyelinase deficiency. These studies demonstrate an important role for
      enzymatic processing of sphingomyelin-to-ceramide by acid-sphingomyelinase as a
      mechanism for generating a portion of the stratum corneum ceramides for
      permeability barrier homeostasis in mammalian skin.

PMID- 10951285
TI  - The heritability of polymorphic light eruption.
AB  - Polymorphic light eruption is classified as an acquired idiopathic
      photodermatosis, yet it appears to cluster in families, suggesting a possible
      genetic component. In this study, we assess the heritability of polymorphic light
      eruption using the classical twin model. Polymorphic light eruption was
      investigated by a nurse-administered questionnaire in a sample of 420 pairs of
      adult female twins from St Thomas' Hospital UK Adult Twin Registry, including 119
      monozygotic and 301 dizygotic pairs. Probandwise concordance for the presence and
      absence of disease was calculated and the heritability of polymorphic light
      eruption assessed by a quantitative genetic model fitting approach using Mx
      software. The prevalence of polymorphic light eruption was 21% and 18% in
      monozygotic and dizygotic twins, respectively. A family history of polymorphic
      light eruption in first-degree relatives (not including the cotwin) was present
      in 12% of affected twin pairs (where at least one twin had polymorphic light
      eruption) compared with 4% of unaffected twin pairs, providing evidence of
      familial clustering (p < 0.0001). The probandwise concordance for polymorphic
      light eruption was higher in monozygotic (0.72) than in dizygotic twin pairs
      (0.30), indicating a strong genetic effect. Quantitative genetic modeling found
      that a model comprising additive genetic (A) and unique environmental (E) factors
      provided the most parsimonious fit, although a dominant gene effect could also
      explain our data. In the AE model, 84% (95% confidence interval 65-94%) of the
      variance in susceptibility to polymorphic light eruption is attributed to
      additive genetic factors with the remaining 16% (95% confidence interval 6-35%)
      to unique environmental effects. These data establish a clear genetic influence
      in the expression of polymorphic light eruption and provide a basis for examining
      candidate genes that may be pathogenic in this common condition.

PMID- 10951286
TI  - Genetic modeling of abnormal photosensitivity in families with polymorphic light
      eruption and actinic prurigo.
AB  - Actinic prurigo and polymorphic light eruption are two of the so-called
      idiopathic photodermatoses, resulting from abnormal cutaneous responses to
      ultraviolet radiation (photosensitivity). Whereas they are clinically distinct in
      most cases, there are sufficient similarities between them to suggest they may be
      related conditions. To take this further, we examined the prevalence of
      polymorphic light eruption in families ascertained through actinic prurigo
      probands, as evidence of a shared pathogenesis. We then determined the
      heritability of photosensitivity in 420 individuals from families ascertained
      through polymorphic light eruption and actinic prurigo probands using segregation
      analysis. Across 58 pedigrees the prevalence of photosensitivity in first-degree
      relatives was 20.9% compared with a population prevalence of 13.6%, giving a
      relative risk of 1.5 (confidence interval 1.15-2.0) and providing evidence of
      clustering within families. The prevalence of photosensitivity (predominantly
      polymorphic light eruption) in relatives of actinic prurigo probands was 23.7%,
      with a relative risk of 1.74 (confidence interval 1.24-2.36). Modeling for
      polymorphic light eruption across all pedigrees revealed a strong genetic
      component with polymorphic light eruption showing a dominant mixed mode of
      inheritance. The model parameters estimate that 72% of the U.K. population carry
      a low penetrance polymorphic light eruption susceptibility allele, but that among
      this highly prevalent genotype only 24% of susceptible females and 13% of
      susceptible males will have polymorphic light eruption. Expression of polymorphic
      light eruption in genetically susceptible individuals (intergenotype variance) is
      determined in large part by a polygenic component, with an important additional
      environmental component. In summary, this study provides clear evidence that
      polymorphic light eruption is an inherited condition. It also suggests that
      polymorphic light eruption and actinic prurigo share a common genetic background,
      supporting the view that actinic prurigo may represent a human leukocyte antigen
      restricted subset of polymorphic light eruption.

PMID- 10951287
TI  - Biochemical characterization of S100A2 in human keratinocytes: subcellular
      localization, dimerization, and oxidative cross-linking.
AB  - S100A2 is a calmodulin-like protein of unknown function, whose transcription is
      positively regulated in response to ErbB and p53 signaling. Expression of S100A2
      is markedly increased in the context of ErbB-driven reactive epidermal
      hyperplasia, and decreased in the context of hypofunctional p53 mutations in
      carcinoma cell lines and tumors. This bimodal pattern of regulation suggests an
      important function for S100A2 in keratinocyte differentiation and carcinogenesis.
      Taking the biochemical approach to the determination of S100A2 function, we have
      characterized its physical state and subcellular localization in normal human
      keratinocytes. S100A2 in hypotonic lysates remained soluble after centrifugation
      at 100 000 x g, indicating that it is not associated with cell membranes.
      Permeabilization experiments confirmed the lack of membrane association and
      revealed a digitonin-insoluble nuclear fraction of S100A2, which was confirmed by
      immunofluorescence microscopy. Pulldown assays of epitope-tagged S100A2 and yeast
      two-hybrid screening revealed that S100A2 displays a strong propensity to
      homodimerize. Naturally expressed S100A2 dimers in normal human keratinocytes
      readily underwent intermolecular disulfide cross-linking unless a strong
      denaturant was present during cell lysis. Treatment of intact normal human
      keratinocytes with hydrogen peroxide strongly promoted S100A2 cross-linking.
      These results demonstrate that native S100A2 is a homodimer that does not depend
      on disulfide cross-linking for stability, but undergoes intermolecular cross
      linking at cysteine residues in response to oxidative stress. Based on these
      findings, we propose that S100A2 may protect normal keratinocytes against
      carcinogens by participating in the cellular proof-reading response to oxidative
      stress.

PMID- 10951288
TI  - Leukemia inhibitory factor induces epidermal hyperplasia in patients with
      amyotrophic lateral sclerosis.
AB  - We investigated the biochemical and morphologic alteration in skin of amyotrophic
      lateral sclerosis patients. We found an obvious high expression of leukemia
      inhibitory factor and distinct epidermal hyperplasia in the skin of amyotrophic
      lateral sclerosis patients compared with disease controls. The thickness and cell
      density, as well as the leukemia inhibitory factor immunostain density, of the
      epidermis in amyotrophic lateral sclerosis patients correlated positively with
      duration of illness. The striking fact was the significant epidermal hyperplasia
      correlating with leukemia inhibitory factor expression in amyotrophic lateral
      sclerosis patients (r = 0.94, p < 0.001). In vitro experiments revealed that
      leukemia inhibitory factor stimulated keratinocyte proliferation in primary
      keratinocyte culture and induced epidermal hyperplasia in skin organ culture.
      These findings lead to the hypothesis that a high expression of leukemia
      inhibitory factor is closely associated with epidermal hyperplasia in amyotrophic
      lateral sclerosis patients.

PMID- 10951289
TI  - A sensitive gas chromatography-mass spectrometry assay reveals increased levels
      of monohydroxyeicosatetraenoic acid isomers in human plasma after extracorporeal
      photoimmunotherapy and under in vitro ultraviolet A exposure.
AB  - Extracorporeal photoimmunotherapy (photopheresis) is a highly effective therapy
      in the treatment of various disorders. Although extracorporeal photoimmunotherapy
      has been successfully used for more than 10 y, its mechanism of action is still
      unclear. The formation of reactive oxygen species have been implicated in
      extracorporeal photoimmunotherapy, but malonyl dialdehyde as a marker of systemic
      lipid peroxidation did not increase significantly during treatment. To
      investigate further the involvement of reactive oxygen species in extracorporeal
      photoimmunotherapy, we have introduced a highly sensitive negative ion gas
      chromatography-mass spectrometry based method for quantitating oxygenated
      arachidonic acid isomers (hydroxyeicosatetraenoic acids) in plasma samples of
      patients treated with extracorporeal photoimmunotherapy. In the plasma of healthy
      volunteers pmole amounts of 2-, 3-, 5-, 8-12-, and 15-hydroxyeicosatetraenoic
      acid were detected and we observed a dose-dependent augmentation in these
      metabolites when the blood was irradiated with increasing doses of ultraviolet A
      in the presence of the photosensitizer 8-methoxypsoralen. Analysis of plasma
      samples obtained from patients before and after extracorporeal photoimmunotherapy
      revealed a characteristic increase in total hydroxyeicosatetraenoic acid levels,
      particularly of 5-hydroxyeicosatetraenoic acid which contributed 80% to the sum
      of all hydroxyeicosatetraenoic acid isomers. Chiral phase high-performance liquid
      chromatography indicated almost equal amounts of 5S- and 5R
      hydroxyeicosatetraenoic acid suggesting that the majority of lipid peroxidation
      products are formed via nonenzymatic oxidation reactions.

PMID- 10951290
TI  - Peripheral blood T cell clonality in mycosis fungoides -an independent prognostic
      marker?

PMID- 10951291
TI  - Envoplakin and periplakin, the paraneoplastic pemphigus antigens, are also
      recognized by pemphigus foliaceus autoantibodies.

PMID- 10951292
TI  - Gratitude and a new generation

PMID- 10951293
TI  - Early screening for amblyogenic risk factors lowers the prevalence and severity
      of amblyopia.
AB  - PURPOSE: To evaluate the efficacy of a mass screening program for amblyopia and
      amblyogenic risk factors in infants. METHODS: Since 1968, children between the
      ages of 1 and 2(1/2) years in the city of Haifa, Israel, have been systematically
      screened for amblyopia and amblyogenic risk factors. The screening is performed
      by the Ophthalmology Department of Bnai-Zion Medical Center (formerly known as
      Rothchild Hospital). In 1995, we compared the prevalence and severity of
      amblyopia in two populations of 8-year-old children in elementary school: one
      group was a cohort of 808 children from the city of Haifa and its vicinity, who
      had been screened in infancy (between 1988 and 1990); and the second group, the
      control group, was a cohort of 782 children from Hadera and its vicinity, where
      this early screening program is not conducted. Amblyopia was defined as corrected
      visual acuity of < or =5/10 (20/40), or >1 line difference in corrected visual
      acuity between the two eyes. Referral rate, treatment rate, sensitivity,
      specificity, and positive predictive value and negative predictive value of the
      screening test in detecting factors that later resulted in the development of
      amblyopia were examined. RESULTS: The prevalence of amblyopia in the 8-year-old
      population screened in infancy was found to be 1.0% compared with 2.6% in the 8
      year-old population that had not been screened in infancy (P =.0098). The
      prevalence of amblyopia with visual acuity of < or =5/15 (20/60) in the amblyopic
      eye was 0.1% in the screened population compared with 1.7% in the non-screened
      population (P =.00026). In the screened infant population, 3.6% were referred
      from the screening examination to a confirmatory examination and 2.2% were
      treated. The screening examination had a sensitivity of 85.7% and a specificity
      of 98.6% for amblyopia. The positive predictive value of the screening
      examination was 62.1% and the negative predictive value was 99.6%. CONCLUSIONS:
      The screening program for amblyopia and amblyogenic risk factors in infants,
      followed by appropriate treatment, is effective in significantly reducing the
      prevalence and severity of amblyopia in children.

PMID- 10951294
TI  - Clinical and electroretinographic findings in fetal alcohol syndrome.
AB  - PURPOSE: Fetal exposure to alcohol is a serious public health problem and is
      associated with anomalies of the eye ground, as well as neurodevelopmental delay,
      growth delay, and characteristic facial features. Our purpose is to report the
      incidence of abnormal electroretinogram (ERG) results in children with fetal
      alcohol syndrome and raise awareness of the diagnosis of fetal alcohol syndrome
      in ophthalmology. METHODS: A retrospective review was performed on the records of
      11 children with the diagnosis of fetal alcohol syndrome. The results of the
      ophthalmologic examination, magnetic resonance imaging, visual acuity test, and
      ERG are reported. RESULTS: The magnetic resonance imaging results were abnormal
      in all subjects tested. The ophthalmology examination showed optic nerve
      hypoplasia in 91% of the subjects. Visual acuity was reduced in all but one
      subject. The ERG results were abnormal, showing reduced b-wave amplitude,
      increased a- and b-wave implicit time, reduced Rmax, and increased log (k). The
      scotopic ERG was more severely affected than the photopic ERG. CONCLUSIONS:
      Prenatal alcohol exposure can lead to changes in retinal function as evidenced by
      an abnormal ERG response. The ERG can therefore be a tool with which to identify
      suspected alcohol embryopathy.

PMID- 10951295
TI  - Long-term surgical and visual outcomes in primary congenital glaucoma: 360
      degrees trabeculotomy versus goniotomy.
AB  - PURPOSE: To compare the visual outcome and refractive status of children with
      primary congenital glaucoma who underwent 360 degrees trabeculotomy or goniotomy
      as an initial surgical procedure. METHODS: This retrospective study describes 24
      eyes (15 patients) with primary congenital glaucoma that underwent 360 degrees
      trabeculotomy as the initial procedure and 40 eyes (23 patients) that underwent
      goniotomy as the initial procedure. Inclusion criteria were: (1) diagnosis of
      primary congenital glaucoma and initial angle surgery before 1 year of age, (2)
      no other ocular or systemic diseases, (3) 360 degrees trabeculotomy or goniotomy
      as the first surgical procedure, and (4) ability to obtain an Allen or Snellen
      visual acuity. A postoperative vision of 20/50 or better was considered good.
      Surgical success was defined as an intraocular pressure (IOP) less than 22 mm Hg
      with or without medication and without evidence of a progressive optic
      neuropathy. RESULTS: The IOP was successfully controlled in 92% of eyes in the
      trabeculotomy group and in 58% of eyes in the goniotomy group (P =.004). Of eyes
      in the trabeculotomy group, 79% had vision of 20/50 or better compared with 53%
      in the goniotomy group (P =.03). High myopia was more prevalent in the goniotomy
      group, but this difference was not statistically significant (P =.16). A poor
      visual outcome was associated with failure of the angle surgery or poor
      compliance with follow-up and amblyopia therapy. CONCLUSION: For primary
      congenital glaucoma, 360 degrees trabeculotomy is a highly effective procedure
      that results in excellent pressure control and is at least as successful as
      multiple standard procedures. In this study, 360 degrees trabeculotomy resulted
      in better vision than what is reported in the literature for standard angle
      procedures.

PMID- 10951296
TI  - The maximum motor fusion test: a parameter for surgery for acquired esotropia.
AB  - PURPOSE: The purpose of this study was to determine whether surgery for acquired
      esotropia based on the maximum capacity for motor fusion measured with a prism
      bar could be used to increase the number of millimeters of bilateral medial
      rectus recession that could be performed without producing an early
      overcorrection or a late consecutive exotropia, as a way safely to reduce the
      need for postoperative wear of glasses or a bifocal. METHODS: Category I patients
      had residual deviations of esotropia (ET) of 12 PD or more with distance
      fixation, measured after a full hyperopic correction of +1.50 to +3.25 was
      placed, and had no significant anisometropia or astigmatism. Category II patients
      had residual deviations of esotropia of less than 11 PD with distance fixation
      and had residual deviations of esotropia with near fixation (ET') of at least 10
      PD more than esotropia with distance fixation ("clinical high AC/A"). Category
      III patients had had previous bilateral medial rectus muscle recessions and had
      recurrent esotropia with near fixation of more than 10 PD. For patients in
      categories I and II, bilateral medial rectus muscle recessions were performed by
      using a published dose-response table from the national Prism Adaptation Study
      but with the maximum capacity for motor fusion as the input parameter instead of
      the prism-adapted angle. Patients in category III received re-recessions of one
      or both medial rectus muscles, according to a previously published system, with
      the distance fusional amplitude as the input parameter. RESULTS: In category I,
      24 of 30 (80%) patients needed no glasses after surgery, 1 of 30 had esotropia,
      and 2 of 30 had exotropia (XT) (10% reoperation rate). In category II, 35 of 36
      (98%) patients needed no bifocals after surgery, and 3 of 36 had exotropia (9%
      reoperation rate). In category III, 10 of 10 patients needed no bifocals, and 2
      of 10 had exotropia (20% reoperation rate). CONCLUSIONS: When a postoperative
      reduction in dependence on continuous wear of an optical appliance is a
      reasonable goal, the maximum motor fusional capacity, measured with a prism bar,
      is a good parameter for surgical design.

PMID- 10951297
TI  - High-frequency ultrasonography findings in persistent hyperplastic primary
      vitreous.
AB  - PURPOSE: To identify anatomic correlates in eyes with persistent hyperplastic
      primary vitreous (PHPV) by using high-frequency ultrasonography. METHOD: Three
      main groups of patients were studied by means of high-frequency ultrasonography
      over a 19-month period. Group I included 9 eyes of 9 patients with newly
      diagnosed unilateral PHPV. Group II included 4 eyes of 4 patients with unilateral
      PHPV that had been previously surgically treated. Group III included 22 eyes and
      was a control group of patients without PHPV. This group consisted of the 5
      contralateral normal eyes of 5 patients with unilateral PHPV in the fellow eye,
      both eyes of one patient with uncomplicated unilateral cataracts, the affected
      eye of one patient with unilateral uncomplicated cataract, the affected eye of
      one patient with isolated retinal coloboma, and 13 normal eyes of 7 young adults.
      Group I and II patients also had B-scan ultrasonography performed and had any
      intraoperative findings noted. RESULTS: Characteristic features of PHPV, such as
      centrally dragged ciliary processes and swollen anteriorly displaced lens, were
      observed only in those eyes with PHPV. A new echographic finding of a double
      linear echo was observed in the region of the pars plana or plicata only in eyes
      with PHPV. This finding was confirmed intraoperatively to be consistent with a
      thickened adherent anterior hyaloid face and not to be an anteriorly inserted
      peripheral retina. CONCLUSION: High-frequency ultrasound can be reliably used to
      distinguish characteristic features of PHPV. To our knowledge this is the first
      such description of the use of high-frequency ultrasonography in PHPV eyes.
      Furthermore, the presence of a thickened adherent anterior hyaloid face may help
      explain the well-recognized complications of peripheral retinal tears and retinal
      detachments during and after surgical intervention.

PMID- 10951298
TI  - Prognostic significance of vascular dilation and tortuosity insufficient for plus
      disease in retinopathy of prematurity.
AB  - BACKGROUND: Plus disease, one of the most important prognostic indicators in
      retinopathy of prematurity (ROP), is designated as present or absent. A grading
      system based on comparison with standard, high-quality color photographs may be
      useful to more accurately describe the spectrum of vascular dilation and
      tortuosity preceding plus disease, but it is of practical value only if it has
      prognostic significance. We hypothesized that grading of "pre-plus" vascular
      changes can identify eyes at risk for progression to vision-threatening ROP.
      METHODS: Video clips of posterior pole images captured at the examination closest
      to 33 weeks' postconceptional age of 32 infants screened during an 18-month
      period were randomized. Two masked examiners viewed and graded the images in
      comparison with standard photographs representative of 5 distinct grades of
      retinal vascular dilation and tortuosity. A case-control design was used to
      compare the incidence of progression to stage 3 ROP, development of plus disease,
      and requirement of laser treatment between infants with normal posterior poles
      and those judged to have early dilation and tortuosity insufficient for plus
      disease. RESULTS: Of the 8 patients with mild vascular dilation and tortuosity
      insufficient for plus disease, 5 (63%) eventually required laser treatment, 4
      (50%) later developed stage 3 ROP, and 5 (63%) progressed to plus disease. Of the
      24 patients with normal posterior poles, none required laser treatment, 2 (8%)
      developed stage 3 ROP, and none progressed to plus disease. The group with mild
      vascular dilation and tortuosity had a significantly higher incidence of
      progression to laser treatment (P =.0003), stage 3 ROP (P =.027), and plus
      disease (P =.0003). CONCLUSIONS: Early vascular dilation and tortuosity judged
      insufficient for plus disease have prognostic significance in the early course of
      ROP. A grading system that uses standard, high-quality color photographs
      representing the spectrum of "pre-plus" vascular changes has potential utility in
      both the clinical and research settings.

PMID- 10951299
TI  - Treatment of nasolacrimal duct obstruction in children with trisomy 21.
AB  - BACKGROUND: Nasolacrimal duct (NLD) obstruction and tear film abnormalities occur
      frequently in children with trisomy 21. This study describes the outcomes of
      treatment for NLD obstruction in this population. METHODS: The records of 15
      children with trisomy 21 treated for NLD obstruction were reviewed. Eight
      patients were initially treated with NLD probing with or without placement of
      nonfixated lacrimal stents. Because of poor success with this procedure, the
      initial treatment of children with trisomy 21 and NLD obstruction was changed to
      balloon catheter dilation in 1997. Outcomes were considered excellent if the
      patient had complete resolution of epiphora and dacryocystitis, good if the
      patient had only mild residual symptoms, fair if the patient had significant
      residual symptoms, and poor if there was no improvement. RESULTS: Of 8 patients
      treated initially with NLD probing, 5 had fair or poor outcomes. These patients
      all had good outcomes after placement of nasally fixated lacrimal stents, balloon
      catheter dilation, or both. Of 7 patients treated initially with balloon catheter
      dilation, 5 had excellent or good outcomes and 2 had fair or poor outcomes.
      CONCLUSION: Simple NLD probing is often unsuccessful in treating NLD obstruction
      in children with trisomy 21. Balloon catheter dilation appears to be a reasonable
      alternative first treatment in these patients.

PMID- 10951301
TI  - Good visual function in posterior microphthalmos.
AB  - Posterior microphthalmos is a rare condition in which the anterior segment is
      normal in size and configuration, but the posterior segment is reduced in size;
      this results in axial hyperopia and retinal folding. Patients have decreased
      vision that is caused by posterior segment abnormalities, high refractive error,
      and amblyopia. We present a case of posterior microphthalmos in which retinal
      function was relatively intact and visual loss was believed to be primarily
      caused by refractive error and amblyopia. After treatment, the child's visual
      acuity and school performance improved. This case emphasizes the need for careful
      examination, refraction, and follow-up for these children because their visual
      potential may be reasonably good.

PMID- 10951300
TI  - Facial asymmetry in superior oblique muscle palsy and pulley heterotopy.
AB  - INTRODUCTION: Some observers have considered facial asymmetry as characteristic
      of congenital superior oblique muscle (SO) palsy. However, recent orbital imaging
      studies have determined that incomitant vertical strabismus resembling SO palsy
      can be caused by heterotopic rectus muscle pulleys. This finding suggests that
      facial asymmetry may predict the presence of abnormal orbital anatomy rather than
      be secondary to ocular torticollis. METHODS: Subjects who underwent orbital
      computed tomography or magnetic resonance imaging were divided into 5 groups
      based on clinical evaluation and previously established imaging criteria: (1)
      congenital SO palsy; (2) acquired SO palsy; (3) strabismus with pulley
      heterotopy; (4) strabismus without SO palsy or pulley heterotopy; and (5)
      orthotropic subjects. Frontal photographs were digitized and the following 3
      facial morphometric features recorded: (1) angle of inclination of each orbit;
      (2) relative facial size; and (3) facial angle. RESULTS: The 79 subjects who
      underwent imaging were divided into the 5 groups as follows: 6 with congenital SO
      palsy; 7 with acquired SO palsy; 20 with pulley heterotopy; 26 with strabismus
      without SO palsy or pulley heterotopy; and 20 control subjects. All subjects with
      either congenital or acquired SO palsy had torticollis. Multivariate analysis
      demonstrated no significant differences in any of the 3 facial morphometric
      features among any of the groups. CONCLUSION: Facial asymmetry as assessed by
      these 3 morphometric features is not useful in distinguishing between congenital
      SO palsy or pulley heterotopy and other acquired forms of strabismus. This
      finding casts doubt on the relationship between ocular torticollis and facial
      asymmetry.

PMID- 10951302
TI  - A patient with de Morsier and Duane syndromes.
AB  - de Morsier syndrome, or septo-optic dysplasia, is a developmental malformation
      complex characterized by optic nerve hypoplasia, dysgenesis of the septum
      pellucidum, and hypothalamic-pituitary dysfunction. (1,2) In Duane retraction
      syndrome, there is absence of the sixth nerve nucleus with congenital retraction
      of the globe and narrowing of the lid fissure in adduction, frequent abduction
      deficiency, and variable limitation to adduction of the affected eye. (3) The
      purpose of this report is to present a patient with the uncommon and previously
      unreported concurrence of both of these congenital malformation complexes,
      presumably because of a common disturbance of neuronal development.

PMID- 10951303
TI  - Medial transposition of the lateral rectus muscle in combined third and fourth
      nerve palsy.
AB  - Surgical treatment of combined third and fourth nerve palsy is a challenging
      problem in strabismology. Five of the 6 extraocular muscles are paralyzed, which
      leaves the lateral rectus muscle with no antagonist to counteract its activity
      and usually results in a maximal exotropia. The goal of surgery is to achieve
      orthophoria in primary position with limited ductions. Because some believe that
      a conventional recession-resection procedure will inevitably result in a drift
      back to exotropia,(1) several other methods have been proposed to treat this
      disorder. These include temporal mattress suture,(2) eye muscle prosthesis, (3,4)
      splitting and reattaching the lateral rectus muscle near the vortex veins,(5) and
      fixation of the eye with fascia lata.(6) Taylor(7) suggested using medial
      transposition of the lateral rectus muscle in a case of isolated third nerve
      palsy. We report the outcome of a procedure that included such a transposition
      for the treatment of combined third and fourth nerve palsy.

PMID- 10951304
TI  - Ophthalmic manifestations of Angelman syndrome.
AB  - In 1965, Angelman described 3 cases of what he called "Puppet" children, named
      for the characteristic signs associated with what is now known as Angelman
      syndrome, including mental retardation, speech impairment, easy excitability, and
      frequent spontaneous laughter.(1) Since that report, much progress has been made
      in defining the syndrome's clinical manifestations and understanding its
      molecular foundations, including identification of deletions of 15q11-13 in some
      patients. There are few reports in the ophthalmic literature regarding ocular
      manifestations of this syndrome. (2,3) We present the case of a child with
      strabismus associated with Angelman syndrome, and we review the ophthalmic and
      systemic findings, as well as recent advances in molecular genetics, in these
      patients.

PMID- 10951305
TI  - Treatment of subtotal medial rectus myectomy complicating functional endoscopic
      sinus surgery.
AB  - During the past 2 decades, the introduction of functional endoscopic sinus
      surgery (FESS) has dramatically improved the treatment of sinus disorders.
      However, a variety of orbital complications have been reported, including optic
      nerve damage, hemorrhage, infection, compromise of the lacrimal drainage
      apparatus, and strabismus. At least 10 cases have reported damage to the medial
      rectus muscle. (1-8) Treatment options for such patients have been limited,
      especially because most are adults at risk for anterior segment ischemia after
      transposition of vertical rectus muscles. We describe 2 patients whose medial
      rectus myectomies were repaired by using nonabsorbable "hang-back" sutures in
      combination with a botulinum toxin (Botox) injection of the antagonist lateral
      rectus muscle. Good primary position alignment was achieved in both patients, and
      one patient was able to regain binocular function. We recommend this surgical
      approach, especially in patients at increased risk for anterior segment ischemia.

PMID- 10951306
TI  - Dissociated vertical deviation remains a moving target.

PMID- 10951307
TI  - The JMPT goes online

PMID- 10951308
TI  - Effects of side-posture positioning and side-posture adjusting on the lumbar
      zygapophysial joints as evaluated by magnetic resonance imaging: a before and
      after study with randomization.
AB  - OBJECTIVE: To test the a priori hypothesis that one of the positive mechanisms of
      action of chiropractic side-posture manipulation (adjusting) of the lumbar spine
      is to separate, or gap, the zygapophysial (Z) joints. DESIGN: Before and after
      study with randomization. SETTING: Chiropractic college clinic and magnetic
      resonance imaging (MRI) facility. PARTICIPANTS: Sixteen healthy student
      volunteers (8 men and 8 women) ages 22 to 29 years with no history of significant
      low back pain. Nineteen volunteers were screened, with 3 disqualified from the
      study. Subjects were randomized into 4 groups, each with 2 men and 2 women.
      INTERVENTIONS: Lumbar side-posture spinal adjusting (manipulation) and side
      posture positioning. MAIN OUTCOME MEASURES: Comparison of anterior to posterior
      measurements of the Z joints from MRI scans taken before and after side-posture
      spinal adjusting and before and after side-posture positioning, and a rigorous
      subjective evaluation protocol of the Z joints by 3 radiologists blinded to the
      randomized groups. MAIN RESULTS: Observers making measurements were blinded to
      what group subjects were placed in and whether they were measuring first or
      second scans; radiologists were blinded to what group subjects were assigned.
      Differences were found between the groups. Those receiving side-posture spinal
      adjusting and remaining in side posture showed the greatest increase in gapping
      (0.7 mm vs 0.0 mm for controls). CONCLUSIONS: Lumbar side-posture spinal
      adjusting produced increased separation (gapping) of the zygapophysial joints.
      Side-posture positioning also produced gapping, but less than that seen with
      lumbar side-posture adjusting. A larger clinical trial should be performed to
      further define the results of this study.

PMID- 10951309
TI  - Innervation of the human costovertebral joint: implications for clinical back
      pain syndromes.
AB  - BACKGROUND: The diagnosis of pain in the upper back, shoulder, chest, and arm is
      often made with considerable confusion and may be accompanied by needless expense
      and suffering by the patient. Despite the paucity of evidence concerning the
      tissues and mechanisms responsible for interscapular and atypical chest pain or
      "pseudo-angina," practitioners of manual therapy maintain that manipulation of
      the costovertebral elements and associated soft tissues may be helpful in the
      treatment of these painful conditions. OBJECTIVE: We have examined the
      costovertebral complex in humans with respect to the presence of immune-like
      reactivity to neurofilament protein and the neuropeptide substance P and
      calcitonin gene-related peptide, markers that reveal the presence of axons in
      peripheral tissues. DESIGN: Human costovertebral complexes obtained at autopsy
      were processed with standard histologic examination and immunocytochemical
      methods to detect the presence of neurofilaments, substance P, and calcitonin
      gene-related peptide. MAIN OUTCOME MEASURES: Outcomes were descriptive and did
      not require statistical methods. RESULTS: All costovertebral joints contained
      innervation within the anterior capsule and synovial tissues. In 4 separate
      cases, the costovertebral joints contained large intraarticular synovial
      inclusions or "meniscoids" found to contain small bundles of axons with immune
      like reactivity to substance P. Axon bundles were identified in serial section
      with monoclonal antibodies to neurofilaments as well as with urea-silver nitrate
      staining. CONCLUSIONS: The costovertebral joint has been considered a candidate
      for producing back pain and/or pseudo-angina that may be ameliorated by spinal
      manipulation. This study has demonstrated that the costovertebral joint has the
      requisite innervation for pain production in a similar manner to other joints of
      the spinal column.

PMID- 10951310
TI  - Chiropractic rehabilitation of the cervical spine.
AB  - BACKGROUND: Rehabilitation has been a part of chiropractic almost since the
      beginning of the profession. Yet today, relatively few chiropractors provide
      rehabilitation in any systematic way in their practices. The modern era of health
      care calls for all spine specialists to emphasize exercise in their management
      strategies, and the chiropractic profession has the opportunity to establish
      itself as a leader in the area of rehabilitation in patients with spine-related
      disorders. OBJECTIVE: To present the principles and techniques of cervical
      rehabilitation as it is used by the author and explain the rationale for these
      procedures based on current knowledge of the neurophysiology of the cervical
      spine. CONCLUSION: Rehabilitation of the cervical spine can be performed by
      virtually any chiropractor because effective rehabilitative methods can be
      applied with minimal space and equipment. The methods presented here are designed
      to assess several essential functions of the cervical spine and apply procedures
      that are designed to maximize these functions while monitoring the clinical
      response to the management strategy. Future research in this area should provide
      more information about cervical function and assist in the development of
      improved management of patients with cervical spine syndromes.

PMID- 10951311
TI  - Patient-practitioner perceptions: can chiropractors assume congruence?
AB  - BACKGROUND: Advances in mind-body medicine have resulted in the realization that
      beliefs can modulate pathophysiologic processes. Because symbolic interaction
      affects health status, perceptions and the congruence between the perceptions of
      chiropractors and their patients become a relevant clinical consideration.
      OBJECTIVE: A case study to explore the congruence of health-relevant perceptions
      of chiropractors and their patients was undertaken. METHOD: This Australian case
      study was undertaken to explore the concurrence of patient-practitioner
      perceptions with respect to the patient's stress levels, the importance of injury
      as a causative factor in the presenting symptom and the responsibility the
      patient should take "in getting themselves well." Purposive sampling of
      practitioners and convenience sampling of patients was undertaken. Data were
      collected by means of a patient questionnaire and a practitioner questionnaire
      and interview. Data were analyzed to determine the congruence of patient
      practitioner perceptions within each of 173 consultations. RESULTS: A total of 9
      practitioners and 173 patients participated. Within each patient-practitioner
      dyad, congruence of perceptions was <50% in each of 3 dimensions examined. Most
      patients believed they should take a high level of responsibility for "getting
      well." DISCUSSION: Although the results of a case study cannot be extrapolated to
      the chiropractic patient population, this study does suggest that it may be
      prudent for chiropractors to ascertain the extent to which their patients share
      their perceptions of the presenting clinical problem. "Thinking hats" are
      proposed as a helpful perception management tool. CONCLUSION: This exploratory
      study suggests that practitioners should not assume that their patients share
      their perceptions. Given that each patient-practitioner encounter is unique, it
      may be prudent for chiropractors to actively ascertain the patient's opinions. A
      patient's perception of his or her responsibility for "getting well" should be
      harnessed in developing management plans with high compliance.

PMID- 10951312
TI  - Correlation and quantification of relative 2-dimensional projected vertebral
      endplate z-axis rotations with 3-dimensional y-axis vertebral rotations and focal
      spot elevations.
AB  - BACKGROUND: The use of lines erected on the vertebral endplates of the anterior
      to-posterior radiograph to assess z-axis vertebral rotation is a common clinical
      practice. OBJECTIVE: To quantify the projection/distortion error of lateral
      flexion (z-axis rotation) measurement, which results from actual axial (y-axis)
      rotation and changes in focal spot elevation, on AP radiographs. STUDY DESIGN: A
      3-dimensional model of a 4th and 5th lumbar vertebrae was constructed with a
      computer. The angle between the projected inferior vertebral endplate of the 4th
      lumbar vertebra, and the projected superior vertebral endplate of the 5th lumbar
      vertebra was measured. This was done for combinations of 0, 7, 14, and 21 degrees
      of axial (-y-axis) rotation with 0, 15, and 30 cm of elevation of a modeled focal
      spot. RESULTS: An angle was produced between the projected inferior 4th lumbar
      vertebral endplate and the projected superior 5th lumbar vertebral endplate as a
      result of y-axis rotation of the 3-dimensional model. Increasing magnitudes of y
      axis rotation and increasing focal spot elevation produced a lack of confidence
      in this measurement. CONCLUSION: In a clinical setting, limited ranges of y-axis
      rotation have little significant effect on the accuracy of this measurement.
      Increases in y-axis rotation and focal spot elevation can affect measurement
      accuracy.

PMID- 10951313
TI  - Injury threshold: whiplash-associated disorders.
AB  - OBJECTIVES: To review current knowledge and recent concepts of the causes of
      injuries after minor impact automobile collisions and to acquaint those who treat
      these types of injuries with possible injury thresholds and mechanisms that may
      contribute to symptoms. DATA SOURCES: A review of literature involving mechanisms
      of injury, tissue tensile threshold, and neurologic considerations was
      undertaken. A hand-search of relevant engineering, medical/chiropractic, and
      computer Index Medicus sources in disciplines that cover the variety of symptoms
      was gathered. RESULTS: Soft-tissue injuries are difficult to diagnose or
      quantify. There is not one specific injury mechanism or threshold of injury. With
      physical variations of tissue tensile strength, anatomic differences, and
      neurophysiologic considerations, such threshold designation is not possible.
      CONCLUSIONS: To make a competent assessment of injury, it is important to
      evaluate each patient individually. The same collision may cause injury to some
      individuals and leave others unaffected. With the variability of human postures,
      tensile strength of the ligaments between individuals, body positions in the
      vehicle, collagen fibers in the same specimen segment, the amount of muscle
      activation and inhibition of muscles, the size of the spinal canals, and the
      excitability of the nervous system, one specific threshold is not possible. How
      individuals react to a stimulus varies widely, and it is evident peripheral
      stimulation has effects on the central nervous system. It is also clear that the
      somatosensory system of the neck, in addition to signaling nociception, may
      influence the control of neck, eyes, limbs, respiratory muscles, and some
      preganglionic sympathetic nerves.

PMID- 10951314
TI  - Treatment of severe glaucomatous visual field deficit by chiropractic spinal
      manipulative therapy: a prospective case study and discussion.
AB  - OBJECTIVE: To discuss the case of a patient with severely reduced visual fields
      arising from terminal glaucomatous retinal damage and the treatment of this
      condition by spinal manipulation. CLINICAL FEATURES: A 25-year-old uniocular
      female patient with congenital glaucoma sought chiropractic treatment for spinal
      pain, headache, and classic migraine. Advanced optic disk cupping was present,
      and loss of vision was near complete. A 3-degree island of central vision and a
      small area of peripheral light sensitivity had remained relatively stable for 3
      years after a trabeculectomy procedure that had resulted in intraocular hypotony.
      INTERVENTION AND OUTCOME: It was considered possible that chiropractic spinal
      manipulative therapy may have a positive outcome in visual performance. Before
      commencing chiropractic spinal manipulative therapy, an ophthalmologic
      examination was performed, and visual performance was monitored through a course
      of treatment. Immediately after the first treatment, significant visual field
      improvement was recorded in the remaining eye. Maximal improvement of vision was
      achieved after 1 week (4 treatment sessions). Total monocular visual field had
      increased from approximately 2% to approximately 20% of normal. Corrected central
      acuity had improved from 6/12 to 6/9. Independent reexamination by the patient's
      regular ophthalmic surgeon confirmed the results. CONCLUSION: Recovery of vision
      in this patient was an unexpected and remarkable outcome, raising the question of
      whether chiropractic spinal manipulative therapy may be of value in the
      management of glaucomatous visual field loss. More intensive research is
      required.

PMID- 10951315
TI  - Cervical flexion: a study of dynamic surface electromyography and range of
      motion.

PMID- 10951316
TI  - In response

PMID- 10951317
TI  - Structural rehabilitation of the spine and posture: rationale for treatment
      beyond the resolution of symptoms.

PMID- 10951318
TI  - In response

PMID- 10951319
TI  - The influence of a chiropractic manipulation on lumbar kinematics and
      electromyography during simple and complex tasks: a case study.

PMID- 10951321
TI  - Sports chiropractic

PMID- 10951320
TI  - In response

PMID- 10951322
TI  - Chiropractic: A philosophy for alternative health care

PMID- 10951323
TI  - The crystal structure for a depsipeptide Boc-(Leu-Leu-Ala)(2)-(Leu-Leu-Lac)(3)
      OEt with a 3(10)-helical segment.

PMID- 10951324
TI  - Peptides containing the sulfonamide junction. 2. Structure and conformation of Z
      Tau-Pro-D-Phe-NHiPr.
AB  - The taurine (Tau) containing N-protected pseudotripeptide isopropylamide Z-Tau
      Pro-D-Phe-NHiPr (1) has been specifically designed and synthesized as suitable
      model to test the ability of the sulfonamido group to participate as H-bond
      acceptor to a type II beta-turn and to get information on the preferred rotameric
      conformation around the S-N bond and the hybridization state of the nitrogen
      atom. The present structural investigation reveals that, although the sulfonamide
      junction is invariably folded in a gauche mode, the beta-turn structure,
      stabilized by the 4 --> 1 hydrogen bond, is not found in the crystal and the
      sulfonamido oxygen atoms are not involved in any intra- or intermolecular
      hydrogen-bond interaction. More than one conformer populates the CDCl(3) solution
      with only a minor contribution by the expected beta-turn. The Pro nitrogen is
      significantly pyramidalized and the nitrogen lone pair points in opposite
      direction to that of the Pro C(alpha)H bond thus adopting R chirality, in an
      arrangement practically identical to that found in the previously studied
      homochiral analogue Z-Tau-Pro-Phe-NHiPr.

PMID- 10951325
TI  - Globule-coil transition of denatured globular protein investigated by a microwave
      dielectric technique.
AB  - A mechanism for the gel-glass transition of denatured globular protein has been
      explained from the viewpoint of the globule-coil transition with microwave
      dielectric measurements using a time domain reflectometry (TDR) method. Boiled
      egg white, which is an aqueous gel of egg white prepared by heat treatment at 100
      degrees C, becomes a glass on drying. In the gel state, the relaxation processes
      corresponding to the orientation of bulk water and the micro-Brownian motion of
      peptide chains of denatured protein were observed around 10 GHz and 10 MHz,
      respectively. When the gel-glass transition occurred, the relaxation strength for
      bulk water decreased rapidly as evaporation and breaking of water structure
      occurred. Simultaneously, the relaxation strength for micro-Brownian motion
      increased abruptly, as the structure of globular protein varied from globule
      state to coiled state. It is considered that the protein molecule spreads out and
      takes up a coiled state by reductions of hydrophobic and hydrophilic interactions
      of the globular protein. These reductions occur through a decrease in the amount
      of water.

PMID- 10951326
TI  - Hydration of pectic polysaccharides.
AB  - The hydration and swelling of pectic polysaccharides was examined at different
      pHs and ionic strengths as a function of osmotic stress. For weakly charged
      pectic polysaccharides at low concentrations of a monovalent salt (20 mM), the
      main driving force for swelling originates from a polyelectrolyte effect due to
      the translational entropy of ions within the film. Swelling is reduced at higher
      salt concentrations and lower pHs. Polyelectrolyte collapse and minimal swelling
      is observed for more highly charged pectic polysaccharides. Replacement of the
      Na(+) counterion with Ca(2+) results in minimal swelling and the formation of
      network structures even for the weakly charged pectic polysaccharides.

PMID- 10951327
TI  - Dynamic simulation of the mouse prion protein.
AB  - Conformational flexibility in the prion protein is believed to play a role in
      prion diseases. Here we examine the dynamic structure of the mouse cellular prion
      protein using two one-nanosecond molecular dynamics simulations from different
      initial conditions. The two simulations produce similar results. The overall
      structure remains close to that determined by nmr spectroscopy, with small
      deviations arising from loop fluctuation and slight changes in the relative helix
      positions. The sequence dependence of the fluctuation magnitudes is similar to
      the variation between the nmr-derived structure solutions. In both simulations,
      the N-terminal region of the protein forms a short, two-stranded beta-sheet, to
      which a third strand joins after approximately 100 ps. The additional strand may
      reflect nucleative properties of the beta-sheet required for disease-related
      prion conformational change.

PMID- 10951328
TI  - On the transferability of atomic solvation parameters: Ab initio structural
      prediction of cyclic heptapeptides in DMSO.
AB  - A statistical mechanics methodology for predicting the solution structures and
      populations of peptides developed recently is based on a novel method for
      optimizing implicit solvation models, which was applied initially to a cyclic
      hexapeptide in DMSO (C. Baysal and H. Meirovitch, Journal of American Chemical
      Society, 1998, vol. 120, pp. 800-812). Thus, the molecule has been described by
      the simplified energy function E(tot) = E(GRO) + summation operator(k)
      sigma(k)A(k), where E(GRO) is the GROMOS force-field energy, sigma(k) and A(k)
      are the atomic solvation parameter (ASP) and the solvent accessible surface area
      of atom k, respectively. In a more recent study, these ASPs have been found to be
      transferable to the cyclic pentapeptide cyclo(D-Pro(1)-Ala(2)-Ala(3)-Ala(4)
      Ala(5)) in DMSO (C. Baysal and H. Meirovitch, Biopolymers, 2000, vol. 53, pp. 423
      433). In the present paper, our methodology is applied to the cyclic
      heptapeptides axinastatin 2 [cyclo(Asn(1)-Pro(2)-Phe(3)-Val(4)-Leu(5)-Pro(6)
      Val(7))] and axinastatin 3 [cyclo(Asn(1)-Pro(2)-Phe(3)-Ile(4)-Leu(5)-Pro(6)
      Val(7))], in DMSO, which were studied by nmr by Mechnich et al. (Helvetica
      Chimica Acta, 1997, vol. 80, pp. 1338-1354). The calculations for axinastatin 2
      show that special ASPs should be optimized for the partially charged side-chain
      atoms of Asn while the rest of the atoms take their values derived in our
      previous work; this suggests that similar optimization might be needed for other
      side chains as well. The solution structures of these peptides are obtained ab
      initio (i.e., without using experimental restraints) by an extensive
      conformational search based on E(GRO) alone and E(*)(tot), which consists of the
      new set of ASPs. For E(*)(tot), the theoretical values of proton-proton
      distances, (3)J coupling constants, and other properties are found to agree very
      well with the nmr results, and they are always better than those based on E(GRO).

PMID- 10951329
TI  - Conformational studies of parathyroid hormone (PTH)/PTH-related protein (PTHrp)
      chimeric peptides.
AB  - The N-terminal 1-34 segments of both parathyroid hormone (PTH) and parathyroid
      hormone-related protein (PTHrP) bind and activate the same membrane-embedded G
      protein-coupled receptor (PTH1 Rc) present on the surface of cells in target
      tissues such as bone and kidney. This binding occurs in spite of major
      differences between the two hormones in their amino acid sequence. Recently, it
      was shown that in (1-34) PTH/PTHrP hybrid peptides, the N-terminal 1-14 segment
      of PTHrP is incompatible with the C-terminal 15-34 region of PTH in terms of
      bioactivity. The sites of incompatibility were identified at positions 5 in PTHrP
      and 19 in PTH. In the present paper we describe the synthesis, biological
      evaluation, and conformational characterization of two segmental hybrids: PTHrP(1
      27)-[Tyr(34)]bPTH(28-34)-NH(2) (hybrid I) and PTHrP(1-18)-[Nal(23),
      Tyr(34)]bPTH(19-34)-NH(2) (hybrid II). Hybrid I is as active as PTH(1-34)NH(2)
      and more than two orders of magnitude more active than hybrid II. The
      conformational properties of the hybrids were studied in water/trifluoroethanol
      (TFE) mixtures and in aqueous solutions containing dodecylphosphocholine (DPC)
      micelles by CD, two-dimensional nmr and computer simulations. Upon addition of
      TFE to the aqueous solution, both hybrids undergo a coil-helix transition. The
      helix content in 1:1 water/TFE obtained by CD data is about 75% for both hybrids.
      In the presence of DPC, helix formation is observed at detergent concentrations
      above critical micellar concentration and the maximum helix content is of
      approximately 35 and approximately 30% for hybrid I and II, respectively.
      Combined nmr analysis, distance geometry, and molecular dynamics calculations
      suggest that, in both solvent systems, the biologically active hybrid I exhibits
      two flexible sites, centered at residues 12 and 19, connecting helical segments.
      The flexibility point at position 19 is not present in the poorly active hybrid
      II. Our findings support the hypothesis, proposed in our previous work, that in
      bioactive PTH analogues the presence and location of flexibility points between
      helical segments are essential for enabling them to fold into the bioactive
      conformation upon interaction with the PTH1 receptor.

PMID- 10951330
TI  - A model for type II collagen fibrils: distinctive D-band patterns in native and
      reconstituted fibrils compared with sequence data for helix and telopeptide
      domains.
AB  - The periodical D-band pattern is generally considered a unique ultrastructural
      feature shared by all fibril-forming collagens, which correlates with the
      intrafibril, paracrystalline array of tropocollagen monomers. Distinct band
      patterns have been reported, however, for collagen stained long-spacing (SLS)
      crystallites of genetic types I, II, and III. Moreover, D-band patterns of
      negatively stained, native type II collagen fibrils were found to be not
      identical to those of type I in our previous research. Because of (a) these
      distinctive features, (b) tropocollagen heterotrimeric conditions (type I) vs
      homotrimeric conditions (type II), and (c) different lengths and poor homology
      between extrahelical telopeptides, the molecular array or telopeptide
      conformation within the extensively studied type I collagen fibrils could be not
      the same as those in the very much less intensively studied type II collagen
      fibrils. In this investigation, a distinctive positive-staining D-band pattern
      was found for type II collagen fibrils obtained from human cartilages. A fibril
      model was developed by analyzing actual D-band patterns, and matching them
      against simulated patterns based on the primary structure of extrahelical and
      helical domains in human type II tropocollagen. In particular, a more prominent
      b(1) band was apparent in native type II collagen fibrils than in type I. This
      distinctive feature was also observed for native-type collagen fibrils
      reconstituted from purified type II collagen, i.e., free from associated minor
      type XI collagen. On modeling possible monomer arrays, the best fit between
      microdensitograms and simulation traces was found for 234 amino acid staggering,
      as is also the case for type I collagen fibrils. On comparing this model with an
      analogous one for type I collagen fibrils, there was a higher intraband
      distribution of charged residues for band b(1), consistent with the higher
      electrondensity observed for this band in type II collagen fibrils. N- and C
      telopeptide displacement in the model corresponded to D-locations of a c(2)
      subband, which we named c(2.0), and band a(3), respectively. In simulation
      profiles, c(2.0) -like and a(3) -like peaks mimicked the corresponding peaks in
      microdensitograms when molecular reversals were adopted at positions 10N-12N, 12C
      14C, and 17C-19C for N- and C-telopeptides. Hydrophobic interactions and
      algorithmic predictions of protein secondary structure, according to Chou and
      Fasman and Rost and Sander criteria, were consistent with these conformational
      models, and suggest that an additional molecular reversal may occur at positions
      3N-5N. These telopeptide "S-fold" conformations, interpreted as axial projections
      of tridimensional conformation, may represent starting points for further
      investigation into the still unresolved tridimensional conformation of
      telopeptides in monomers arrayed within type II collagen fibrils.

PMID- 10951331
TI  - Model peptide studies of sequence repeats derived from the intracrystalline
      biomineralization protein, SM50. II. Pro,Asn-rich tandem repeats.
AB  - In the biomineralization process, a number of Pro-rich proteins participate in
      the formation of three-dimensional supramolecular structures. One such protein
      superfamily, the Pro,Gly-rich sea urchin intracrystalline spicule matrix
      proteins, form protein-protein supramolecular assemblies that modify the
      microstructure of the inorganic mineral phase (calcite) within embryonic sea
      urchin spicules and adult sea urchin spines. These proteins represent a useful
      model for understanding Pro sequence usage and the resulting generation of
      extended or "open" structures for protein-protein and/or protein-crystal
      recognition. In the sea urchin spicule matrix protein, SM50 (Strongylocentrotus
      purpuratus), there exists an unusual 20-residue Pro,Asn-containing repeat,
      &bond;PNNPNNPNPNNPNNPNNPNPbond which links the upstream 15-residue C-terminal
      domain and the downstream 211-residue beta-spiral repeat domain. To define the
      structural preferences of this 20-residue repeat, we created a 20-residue N- and
      C-terminal "capped" peptidomimetic of this sequence. Using far-uv CD dichroism,
      CH(alpha) and alpha-(15)N conformational shifts, (3)J(NH-CHalpha) coupling
      constants, sequential d(NN(i, i + 1)) rotating frame nuclear Overhauser effect
      connectivities, d(alphaN(i, i + 1))/d(NN(i, i + 1)) intensity ratios, amide
      temperature shift coefficients, amide solvent exchange, and simulated annealing
      refinement protocols, we have determined that this 20-residue repeat motif adopts
      an extended "twist" structure consisting of turn- and coil-like regions. These
      findings are consistent with previous studies, which have shown that Pro-rich
      tandem repeats adopt extended, flexible structures in solution. We hypothesize
      that this 20-residue repeat may fulfill the role of a mineral-binding domain, a
      protein-protein docking domain, or as an internal "molecular spacer" for the SM50
      protein during spicule biocomposite formation.

PMID- 10951332
TI  - Association of latent membrane protein 1 and matrix metalloproteinase 9 with
      metastasis in nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma whose
      consistent association with Epstein-Barr virus (EBV) has been established. Latent
      membrane protein 1 (LMP1), an EBV membrane protein expressed in latent infection,
      is considered to be the EBV oncoprotein. Matrix metalloproteinase 9 (MMP9), one
      of the MMP families, degrades Type IV collagen, a major component of
      extracellular matrix and is believed to be crucial for cancer invasion and
      metastasis. Although MMP9 is reported to be expressed in a variety of cancers, no
      reports concerning NPC have been published to date to the authors' knowledge.
      Recently, the authors have shown that LMP1 induces MMP9 in vitro cell line, which
      suggests the possibility of a mechanism in which LMP1 of EBV contributes to the
      metastasis and tumorigenesis of NPC by the induction of MMP9. METHODS: The
      expressions of LMP1 and MMP9 were immunohistochemically examined in 38 NPC
      sections, and the relation of these proteins were statistically analyzed. The
      authors also analyzed the associations of these proteins with clinical features.
      RESULTS: Both LMP1 and MMP9 proteins were predominantly immunolocalized in cancer
      nests. The expression of MMP9 showed a significant positive correlation with the
      expression of LMP1 (r = 0.75; P < 0.0001). Also, the expression of MMP9
      correlated with lymph node metastasis (P = 0. 0004). CONCLUSIONS: The results
      suggest that the induction of MMP9 by LMP1 contributes to the metastatic
      potential of NPC.

PMID- 10951333
TI  - Distinction of differentiated type early gastric carcinoma with gastric type
      mucin expression.
AB  - BACKGROUND: Intestinal and diffuse gastric carcinomas differ in morphology and
      growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds
      roughly with the intestinal type of Lauren, can demonstrate phenotypic properties
      associated with mucin expression and brush border. However, their clinical
      significance is controversial. A classification based on mucin phenotype and
      brush border was performed to determine the clinicopathologic diversity of DGCs
      in their early stage. METHODS: A total of 120 specimens from 116 DGC patients
      with definite submucosal invasion were evaluated both macroscopically and
      histologically. All sections were examined immunohistochemically with human
      gastric mucin, Muc-2, and CD10 and with mucin histochemically with paradoxical
      concanavalin A staining and high iron Diamine-Alcian Blue. They were classified
      into gastric type (G-type), intestinal type (I-type), mixed gastric and
      intestinal type (M-type), or null type (N-type) phenotypes. The immunoreactivity
      of E-cadherin and beta-catenin also was investigated to determine the correlation
      between mucin phenotype and clinicopathologic factors. RESULTS: The G-type
      phenotype was found to be in contrast to I-type: G-type was an independent factor
      associated with lymph node metastasis. Significant correlations were observed
      between the G-type phenotype and the complex type carcinoma found that was
      histologically: lymphatic invasion, lymph node metastasis, and the abnormal
      expression of E-cadherin. A significant difference in the proportion of mucin
      phenotypes between papillary type and tubular type carcinoma was observed. G-type
      was found to be the predominant phenotype in papillary carcinoma in contrast to
      tubular carcinoma. CONCLUSIONS: The G-type mucin phenotype and papillary
      adenocarcinoma should be distinguished from other types of DGCs because of their
      increased malignant potential in the incipient phase of invasion and metastasis.
      The significance of G-type and papillary adenocarcinoma should be reflected in
      the treatment of patients with early stage DGCs, including endoscopic mucosal
      resection.

PMID- 10951334
TI  - Decreased expression of CD44, alpha-catenin, and deleted colon carcinoma and
      altered expression of beta-catenin in ulcerative colitis-associated dysplasia and
      carcinoma, as compared with sporadic colon neoplasms.
AB  - BACKGROUND: To clarify the cell adhesion status in ulcerative colitis (UC)
      associated colon neoplasm, expression of cell adhesion molecules were
      investigated and compared with that of sporadic colon neoplasm. METHODS: A total
      of 14 low grade dysplasias, 16 high grade dysplasias, and 8 adenocarcinomas
      associated with UC and 17 sporadic adenomas with mild to moderate dysplasia, 22
      adenomas with severe dysplasia, and 15 invasive adenocarcinomas were
      immunohistochemically examined using monoclonal antibodies against CD44, E
      cadherin, alpha- and beta-catenin, and deleted colon carcinoma (DCC). RESULTS:
      CD44, especially its standard form, and DCC expression was stronger in the
      sporadic colon neoplasms than in the UC-associated lesions. Although E-cadherin
      did not show significant differences between the two cases, alpha-catenin was
      more expressed in sporadic colon adenomas with severe dysplasia and carcinomas
      than in their UC-associated counterparts. Membranous beta-catenin staining was
      stronger in UC-associated neoplasms, whereas sporadic lesions had greater
      cytoplasmic and nuclear expression. CONCLUSIONS: The differences in cell adhesion
      molecule expression suggests that UC-associated and sporadic colon neoplasms
      arise from different pathways of tumorigenesis.

PMID- 10951335
TI  - Increased cancer risk in offspring of women with colorectal carcinoma: a Swedish
      register-based cohort study.
AB  - BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the
      Western population, and a considerable proportion of colorectal carcinomas are
      estimated to have a familial background. METHODS: Individuals whose mothers were
      diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of
      1. 48 million person-years, constituted the cohort of this Swedish population
      based register study. The children were born during the period 1941-1993, and the
      cancer incidence was observed during the period 1961-1993, with the expected
      national Swedish incidence used as a reference. RESULTS: A significantly
      increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was
      observed in the cohort. The cancer risk was more pronounced in children whose
      mothers were age < 50 years at the time of diagnosis or had developed
      metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied
      an increased risk for both colon tumors and rectal tumors, the offspring of women
      who were diagnosed with rectal carcinoma were at increased risk of developing
      rectal carcinoma, but no significantly altered risk of colon carcinoma was
      observed. In the cohort, the cumulative risk for colorectal carcinoma before age
      50 years was increased about 3.0 times compared with the general population.
      CONCLUSIONS: This report shows a significant familial aggregation of colorectal
      carcinoma, demonstrates possible differences in hereditary pattern between colon
      carcinoma and rectal carcinoma, and confirms that younger age at the time of
      diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.

PMID- 10951336
TI  - Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity
      of gemcitabine in patients with chemotherapy-naive, advanced hepatocellular
      carcinoma (HCC). METHODS: Twenty-eight patients with unresectable and
      nonembolizable HCC who had received no prior systemic chemotherapy and with
      objectively measurable tumors, adequate liver and renal function, and adequate
      bone marrow reserve were enrolled on this study. The therapy consisted of
      gemcitabine 1250 mg/m(2) intravenously over 30 minutes weekly in an outpatient
      clinic. One course of treatment included three consecutive weekly infusions of
      gemcitabine and a 1-week rest. Treatment courses were repeated every 4 weeks for
      a total of six courses unless there was prior evidence of progressive disease.
      RESULTS: All 28 patients were evaluable for response and toxicity. A partial
      response (PR) was achieved in 5 patients, for an overall response rate of 17.8%
      (95% confidence interval, 2.7-32.9%). Seven patients had stable disease (25%),
      and 16 patients had disease progression (57.2%). The median survival for all 28
      patients was 18. 7 weeks, and, for those patients who achieved a PR, it was 34.7
      weeks. The median time to progression was 12 weeks. National Cancer Institute
      Common Toxicity Criteria Grade 3-4 toxicity consisted primarily of leucopenia
      (10.7%), anemia (14.3%), thrombocytopenia (10.7%), and hepatotoxicity (14.3%).
      The spectrum of both hematologic and nonhematologic toxicity was mild, with
      thrombocytopenia constituting the dose-limiting side effect. CONCLUSIONS:
      Gemcitabine shows marginal antitumor activity in patients with advanced HCC,
      although the response duration is short-lived. Gemcitabine seems to be
      particularly promising because of its low toxicity profile. Further studies in
      combination with other active agents are warranted.

PMID- 10951337
TI  - Trends in incidence and management of gallbladder carcinoma: a population-based
      study in France.
AB  - BACKGROUND: Little is known, at a population level, about the incidence and
      management of gallbladder carcinoma. The objective of this study was to determine
      trends in incidence, treatment, stage at diagnosis, and prognosis of gallbladder
      carcinoma in a well defined population. METHODS: A series of 484 patients
      diagnosed over a 20-year period (1976-1995) in a French well defined population
      was used. Incidence rates were calculated by gender, age groups, and 5-year
      periods. Prognosis was determined using crude and relative survival rates. A
      multivariate relative survival analysis was performed. RESULTS: Age-standardized
      incidence rates were 0.8 per 100,000 inhabitants for men and 1.5 per 100,000
      inhabitants for women. There were no significant time trends in incidence in both
      genders. The proportion of cases resected for cure increased from 18. 1% (1976
      1980) to 42.4% (1991-1995) (P < 0.001) as well as the proportion of cases limited
      to the gallbladder wall, respectively from 15.7% to 27.8% (P < 0.001). Relative
      survival rates were 16.6% at 1 year and 6.2% at 5 years. Age, stage at diagnosis,
      and period of diagnosis significantly influenced the prognosis of gallbladder
      carcinoma. The 5-year relative survival rate rose from 2.7% (1976-1985) to 10.2%
      (1986-1995). The multivariate analysis showed that age and stage at diagnosis
      were independent prognostic factors. CONCLUSIONS: This study demonstrated that
      gallbladder carcinoma incidence is stable in France and that substantial advances
      in its management have been achieved, but there is evidence that further
      improvements are necessary to increase survival.

PMID- 10951338
TI  - Gemcitabine plus vinorelbine as first-line chemotherapy in advanced nonsmall cell
      lung carcinoma a phase II trial.
AB  - BACKGROUND: Response and survival in patients with advanced or metastatic
      nonsmall cell lung carcinoma (NSCLC) remain poor. As single agents, the
      nucleoside analog gemcitabine, and the semisynthetic vinca alkaloid vinorelbine,
      have been shown to be effective in NSCLC and to have a low toxicity profile.
      METHODS: Fifty-four chemotherapy-naive patients with NSCLC Stage IIIB (any TN3M0
      or T4 any NM0) or IV (any T any NM1) were enrolled in this single-institution
      Phase II study. Gemcitabine 1250 mg/m(2) and vinorelbine 25 mg/m(2) were both
      administered on Days 1 and 8 every 3 weeks for up to 9 courses unless disease
      progression or severe toxicity required their discontinuation. RESULTS: Partial
      tumor regression was observed in 16 patients, for an overall response rate of 30%
      (95% confidence interval, 18.4-46.7%) on an intent-to-treat basis. The median
      time to progression was 5 months (range, 3-20). The median survival was 12 months
      (range, 5-42+); 1-year and 2-year survival rates were 49.1% and 17%,
      respectively. Hematologic toxicity was mild with only 11% of the patients
      developing Grade 3 neutropenia. None of the patients developed any Grade 4
      toxicity. CONCLUSIONS: The combination of gemcitabine plus vinorelbine is
      feasible on an outpatient basis. The good activity and tolerability of the
      regimen make it a suitable candidate for further trials, using platinum-based
      regimens as comparators and possibly selecting elderly and less fit patients.

PMID- 10951339
TI  - p53 mutations do not predict response to paclitaxel in metastatic nonsmall cell
      lung carcinoma.
AB  - BACKGROUND: In vitro data and animal studies suggest that paclitaxel may have a
      unique ability to activate tumor cell apoptosis in the absence of wild-type p53
      function. The authors previously demonstrated that response to paclitaxel and
      concurrent radiation was not affected by p53 mutations in nonsmall cell lung
      carcinoma (NSCLC). We sought to determine whether p53 mutations affect response
      to paclitaxel alone in patients with metastatic NSCLC. METHODS: Twenty-five
      patients with metastatic NSCLC who participated in Brown University Oncology
      Group protocols utilizing single-agent weekly paclitaxel had tumor tissue that
      was adequate for p53 analysis. Tumor tissue was evaluated for p53 gene mutations
      in exons 5 through 8 by single-strand conformation polymorphism analysis.
      Mutations were confirmed by direct sequencing of altered mobility polymerase
      chain reaction products. RESULTS: Mutations in p53 were found in 8 of 25 patients
      (32%). The response rates of 75% for patients with tumors with p53 mutations and
      47% for patients with wild-type p53 do not differ significantly (P = 0.12). The 1
      year survival rates for patients with and without p53 mutation after treatment
      with weekly paclitaxel were 63% (95% confidence interval [CI], 31-100%) and 53%
      (95% CI, 33-86%), respectively. CONCLUSIONS: p53 mutations do not adversely
      affect response to paclitaxel as a single agent in metastatic NSCLC. These
      results provide clinical support for in vitro observations that paclitaxel can
      bypass mutant p53 and lead to tumor cell death by alternate pathway(s).
      Paclitaxel should be considered as a component of treatment for patients with
      metastatic NSCLC with tumors that have p53 mutations.

PMID- 10951340
TI  - A phase II study of paclitaxel-ifosfamide-cisplatin combination in advanced
      nonsmall cell lung carcinoma.
AB  - BACKGROUND: The necessity to develop more effective chemotherapy regimens in
      advanced nonsmall cell lung carcinoma (NSCLC) prompted the authors to evaluate
      the paclitaxel-ifosfamide-cisplatin (PIC) combination, developed on the basis of
      high individual single-agent activity, in vitro synergism, and tolerance as
      determined in a previous Phase I study by the authors. PATIENTS: Eligibility
      criteria included advanced NSCLC (American Joint Committee on Cancer
      [AJCC]/International Union Against Cancer [UICC] Stage III/IV), Eastern
      Cooperative Oncology Group performance status (PS) </= 2, no prior chemotherapy,
      and unimpaired hematopoietic and organ function. Chemotherapy included,
      paclitaxel 175 (in the first 10 patients) or 200 mg/m(2) on Day 1, ifosfamide: 5
      g/m(2) divided over Days 1 and 2, and cisplatin 100 mg/m(2) divided over Days 1
      and 2, recycled every 21 days. Granulocyte-colony stimulating factor was
      administered from Day 4 to 13 or until leukocyte count reached >/= 10,000/microL.
      RESULTS: Fifty patients were entered, and all were evaluable for response and
      toxicity: median age, 58 years (range, 40-72), PS, 1 (range, 0-2), Gender: 44
      males and 6 females, Stages IIIA, 6 patients; IIIB, 17; IV, 27; histologies:
      adenocarcinoma, 27 patients; squamous, 17; large cells, 5; unspecified, 1.
      Metastatic sites at diagnosis included lymph nodes, 33 patients; bone, 6; liver,
      5; brain, 10; lung nodules, 7; adrenals, 6; other, 2. Thirty-two of 50 (64%;
      confidence interval, 50.7-77.3%) evaluable patients responded: 4 complete
      remissions, 28 partial remissions, 13 stable disease, and 5 progressive disease.
      The quality-of-life score improved in 37 of 50 (74%) patients. The median
      response duration was 7 months (range 2-34+); median time-to-progression, 8
      months (range, 1-36+), median overall survival, 12 months (range, 2-36+). One
      year survival was 53%. Grade 3 and 4 toxicities included neutropenia 38 of 50
      patients with 21 developing Grade 4 neutropenia (</= 5 days) and 7 of these
      febrile neutropenia (14%); thrombocytopenia, 4 of 50 patients with 1 Grade 4
      requiring platelet transfusions, 1 Grade 3 neuropathy; Grade 1-2 central nervous
      system toxicity due to ifosfamide was seen in 22 patients, no renal toxicity, 15
      Grade 2 myalgias, 17 Grade 2 diarrhea, and 10 Grade 3 vomiting. CONCLUSIONS: The
      PIC combination appears highly active and tolerable in advanced NSCLC
      administered in the outpatient setting. Future randomized comparisons to other
      current standard regimens in NSCLC will be warranted.

PMID- 10951342
TI  - Prognostic impact of INK4A deletion in Ewing sarcoma.
AB  - BACKGROUND: The primary genetic alteration in > 95% of Ewing sarcomas (ES) is a
      specific fusion of EWS with FLI1 or ERG. Secondary genetic alterations possibly
      involved in progression of ES are not well understood. A recent study found loss
      of the negative cell cycle regulator gene INK4A in 8 of 27 ES samples (30%). To
      confirm these findings and evaluate their prognostic significance, the authors
      studied INK4A deletion in 41 ES samples from 39 patients. METHODS: Using Southern
      blot analysis with an INK4A p16 cDNA probe, the intensity of the INK4A bands in
      ES DNA samples was normalized to that of a control probe and compared with
      nondeleted control DNA; > 50% signal reduction was scored as evidence of
      deletion. All ES tumor DNA samples previously were confirmed to have EWS
      rearrangements on the same Southern blots, using a cDNA probe spanning the EWS
      breakpoint region. RESULTS: Tumors from 7 patients (18%) showed INK4A deletion
      independent of disease stage (localized or metastatic) or sample source (primary
      tumor or metastasis). INK4A was a strong negative factor for disease specific
      survival in univariate analysis (P = 0.001) and in multivariate analysis
      including stage (relative risk = 6; P = 0.001). CONCLUSIONS: INK4A deletions
      appear to be the most frequent secondary molecular genetic alteration found to
      date in ES. Their possible clinical usefulness in identifying a subset of ES
      patients with poor prognosis merits systematic prospective analysis. [See related
      article on pages 783-92.]

PMID- 10951341
TI  - Prognostic impact of P53 status in Ewing sarcoma.
AB  - BACKGROUND: Disease stage at the time of diagnosis and response to therapy are
      the main prognostic factors for patients with Ewing sarcoma or peripheral
      neuroectodermal tumor (ES/PNET). The primary genetic alteration in ES/PNET, the
      fusion of the EWS gene with FLI1 or ERG, is diagnostically highly specific for
      these tumors, and molecular variation in the structure of the EWS-FLI1 fusion
      gene also is of prognostic significance. In contrast, secondary genetic
      alterations, such as P53 alterations, are relatively uncommon in ES/PNET, and
      their prognostic impact has not been extensively studied. METHODS:
      Prechemotherapy, paraffin embedded, nondecalcified, primary tumor material in a
      well-characterized series of 55 patients with ES/PNET with defined EWS-FLI1
      fusion transcripts (32 patients with type 1 and 23 patients with other types) was
      studied retrospectively by immunohistochemical techniques for cell cycle
      regulators and proliferative markers, such as P53, P21(WAF1), and Ki-67, as well
      as by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      (TUNEL) technique for apoptosis. Nuclear P53 expression in > 20% of tumor cells
      was scored as aberrant overexpression. Histologic response to neoadjuvant
      chemotherapy was assessed. RESULTS: Aberrant P53 expression (in > 20% of tumor
      cells) was present in 6 patients (11%) but showed no statistically significant
      correlation with disease stage, tumor size, proliferation rate (Ki-67), apoptotic
      rate (TUNEL), or EWS-FLI1 fusion type. By univariate analysis, the P53 > 20%
      group showed a significantly poorer overall survival among patients with
      localized disease (n = 43 patients) (P = 0.001) and in the entire study group (P
      = 0.01). In multivariate Cox analyses of overall survival, P53 > 20% was the
      strongest negative factor among prognostic factors available at the time of
      diagnosis (P = 0.001; relative risk [RR] = 9) and when chemotherapy response was
      included in the analysis (P53 > 20%: P = 0.01; RR = 10). CONCLUSIONS: P53
      alteration appears to define a small clinical subset of patients with ES/PNET
      with a markedly poor outcome. The current observations warrant a systematic
      prospective study with comprehensive P53 mutation analysis. [See related article
      on pages 793-9, this issue.]

PMID- 10951343
TI  - Surveillance for uterine abnormalities in tamoxifen-treated breast carcinoma
      survivors: a community based study.
AB  - BACKGROUND: Tamoxifen-treated breast carcinoma survivors are at elevated risk of
      endometrial carcinoma. Whether to recommend annual surveillance for uterine
      abnormalities in this population is currently under debate. METHODS: This study
      was a cross-sectional, community-based investigation of tamoxifen use and the
      frequency of surveillance for endometrial carcinomas in 541 women with breast
      carcinoma. Study participants whose breast carcinoma was diagnosed in 1994 were
      interviewed in 1998. Data were collected from a telephone interview and from a
      cancer registry record. Tests for uterine abnormalities, based on participant
      reports of endometrial biopsy and transvaginal ultrasound, were categorized
      according to frequency. Testing for uterine abnormalities was defined as
      irregular if women reported tests once every 3 years, on average, and as regular,
      if they reported annual tests. RESULTS: Forty-nine percent of respondents were
      current tamoxifen users, 12% were former tamoxifen users, and 39% reported never
      taking tamoxifen. Of respondents with a uterus (n = 385), 19% reported irregular
      and 30% regular testing for uterine abnormalities after their breast carcinoma
      diagnosis. Respondents more frequently reported transvaginal ultrasound (37%)
      than endometrial biopsy (29%). Women 65 years of age and older were significantly
      less likely to report regular surveillance for uterine abnormalities (16%) than
      those younger than 65 years (35%). Current tamoxifen users more frequently
      reported regular surveillance (43%) than either former (35%) or never tamoxifen
      users (15%). Multivariable analyses showed tamoxifen users were more likely to
      have regular (odds ratio [OR], 9.8; 95% confidence interval [CI], 4.4-21.8) or to
      have irregular testing for uterine abnormalities (OR, 3.9; 95% CI, 1.9-8.1)
      compared with women who never used tamoxifen, after adjustment for age, number of
      recent gynecologic visits, and gynecologic symptoms. CONCLUSIONS: The results of
      the current study indicate that half of the breast carcinoma survivors in this
      population were tested for uterine abnormalities. Although at increased risk, 38%
      of tamoxifen users never had a test. Clear guidelines need to be established for
      the type and frequency of testing for uterine abnormalities among tamoxifen
      treated breast carcinoma patients.

PMID- 10951344
TI  - Novel germline BRCA1 mutations detected in women in singapore who developed
      breast carcinoma before the age of 36 years.
AB  - BACKGROUND: In recent years, although BRCA1 has been extensively investigated,
      the contribution of inherited BRCA1 mutations to breast carcinoma in Asian
      populations is largely unknown. The authors undertook this study to determine the
      prevalence and spectrum of germline BRCA1 mutations among women in Singapore with
      early onset breast carcinoma. METHODS: Forty-three of 72 eligible patients whose
      breast carcinoma was diagnosed before the age of 36 years were studied,
      independent of family history. DNA samples from 50 unrelated individuals randomly
      selected from the National Thalassemia Registry served as controls. Mutational
      screening was performed by single-strand conformation polymorphism analysis and
      protein truncation test, and alterations were confirmed by sequencing. First
      degree relatives of patients with definite BRCA1 mutations were offered
      screening. RESULTS: A total of 6 novel alterations in BRCA1 were identified,
      including 2 frameshift mutations in exon 11 (2846insA and 2885delA), 3 rare
      sequence variants, and 1 polymorphism. Three women (7%) carried deleterious
      mutations, and the mutation was present in at least 1 unaffected first-degree
      relative of the proband. The same mutation (2846insA) was identified in 2 of the
      7 unrelated subjects of Malay ethnicity. One mutation and three rare variants
      were identified in four women with no family history of breast or ovarian
      carcinoma whereas all women with affected first-degree relatives did not harbor
      BRCA1 mutations. No mutation was identified in the controls. CONCLUSIONS: The
      spectrum of germline BRCA1 mutations among the patients in this study was
      distinct from that in Caucasian populations although a similar prevalence was
      observed. Larger studies are necessary to clarify the significance of the
      mutation 2846insA in the Malay community and the penetrance of specific mutations
      in the Singapore population.

PMID- 10951345
TI  - ICI 182,780 (Faslodex): development of a novel, "pure" antiestrogen.
AB  - BACKGROUND: The nonsteroidal antiestrogen tamoxifen is well established as an
      effective treatment for patients with breast carcinoma, both for the treatment of
      metastatic disease and as an adjuvant to surgery for patients with primary breast
      carcinoma. In addition to exerting antagonistic effects on the estrogen receptor,
      tamoxifen and its derivatives act as partial agonists on certain tissues. These
      agonistic effects, for example, endometrial stimulation and stimulation of tumor
      growth after previous response to tamoxifen, may limit their clinical efficacy.
      ICI 182,780 (Faslodex) from AstraZeneca (Cheshire, United Kingdom) is a novel,
      steroidal estrogen antagonist that was designed to be devoid of estrogen agonist
      activity in preclinical models. METHODS: ICI 182,780 was tested in a large number
      of in vitro and in vivo preclinical models, and its value was assessed clinically
      when administered before surgery for breast carcinoma and hysterectomy for benign
      conditions and after failure of tamoxifen in patients with advanced breast
      carcinoma. RESULTS: All data indicated that ICI 182,780 is devoid of agonist
      activity in preclinical models and in clinical trials. It inhibits growth of the
      breast and endometrium. In animal models, it does not cross the blood-brain
      barrier and appears to be neutral with respect to lipids and bone. ICI 182,780
      down-regulates the estrogen receptor and is active in tamoxifen-resistant breast
      carcinoma. In a small, Phase II study, durable responses were seen: Phase III
      clinical trials are in progress comparing ICI 182,780 with anastrozole and
      tamoxifen in the treatment of patients with advanced breast carcinoma.
      CONCLUSIONS: ICI 182,780 specifically down-regulates the estrogen receptor and,
      thus, represents the first of a new class of therapeutic agents. In this report,
      the authors present the current evidence that distinguishes ICI 182,780 from
      tamoxifen and related nonsteroidal compounds and establishes ICI 182,780 as the
      first in a new class of therapeutic agents.

PMID- 10951347
TI  - Pelvic nerve plexus trauma at radical hysterectomy and simple hysterectomy: the
      nerve content of the uterine supporting ligaments.
AB  - BACKGROUND: A major cause of the pelvic morbidity after a radical hysterectomy
      (RH) is thought to be damage to the pelvic nerve plexus, but direct evidence is
      lacking. We set out to determine the nerve content of the uterosacral ligaments
      (USLs) and cardinal ligaments (CLs) at the level at which they are divided during
      a radical hysterectomy and a simple hysterectomy. METHODS: Intraoperative cross
      sectional biopsies were collected from the lateral third of the uterosacral
      ligaments (USLs) and cardinal ligaments (CLs) in 20 women undergoing radical
      hysterectomy (RH) and from the uterine insertion of these ligaments in 11 women
      undergoing a simple hysterectomy. Quantitative immunocytochemistry was utilized
      to demonstrate and quantify the nerve content of the uterine supporting ligaments
      at the level at which they are divided in a RH and in a simple hysterectomy.
      Indirect immunofluorescence staining of frozen cryostat sections was performed
      using primary antibodies to PGP 9.5 (a pan-neuronal marker). A computer-assisted
      image analyzer measured the percentage area of immunoreactivity (PAI) that was
      used to quantify the nerve density. Confocal microscopy was used to determine the
      composition and spatial arrangement of nerve fibers in the ligaments. RESULTS:
      The PAI was significantly greater in the RH biopsies than in the simple
      hysterectomy biopsies, for both the CLs (P < 0.001) and the USLs (P < 0.001). In
      the RH biopsies, more nerve tissue was present in the USL than CL (P = 0.01), and
      compared with the CL more of the nerve fibers in the USL were concentrated in
      large trunks. Excluding these trunks and autonomic ganglia, the free nerve
      content of the USL was lower than that of the CL (P < 0.001). The presence of
      nerve trunks, autonomic ganglia, and free nerve fibers within the lateral third
      of the USL and CL is consistent with extension of the inferior hypogastric plexus
      along these ligaments to the pelvic organs. CONCLUSIONS: The uterine supporting
      ligaments contain autonomic nerves and ganglia, as extensions of the inferior
      hypogastric plexus. The USLs have a greater nerve density than the CLs. Because
      RH disrupts more nerve tissue than a simple hysterectomy, these data provide
      further evidence for the neurogenic etiology of pelvic morbidity after RH.

PMID- 10951346
TI  - Evaluation of alternative methods of cervical cancer screening for resource-poor
      settings.
AB  - BACKGROUND: Noncytologic methods of screening for cervical carcinoma and its
      precursor lesions are needed for resource-poor settings in which cervical
      carcinoma continues to be an important cause of morbidity and mortality. METHODS:
      Two thousand nine hundred forty-four women ages 35-65 years were recruited from
      Cape Town, South Africa and screened using a combination of a Papanicolaou (Pap)
      smear, human papillomavirus (HPV) DNA testing, direct visual inspection after the
      application of a 5% acetic acid solution (DVI), and cervicography. Cervicography
      was considered primarily as a method with which to quality control the DVI
      examinations. Women with squamous intraepithelial lesions (SIL) or carcinoma on
      Pap smear, positive DVI examination (acetowhite lesion or cervical ulcer/growth),
      high levels of high risk HPV DNA (relative light units [RLU] > 10x positive
      control), or positive Cervigramtrade mark were referred for colposcopy and
      cervical biopsy. RESULTS: Pap smears were positive in 8.1% of all women screened
      and identified 65 (78%) of all cases of biopsy confirmed high grade disease (high
      grade SIL or invasive carcinoma). DVI and cervicography were classified as
      positive in 18.1% and 10.5%, respectively, of women screened and identified 58
      (67%) and 46 (58%) of all cases of high grade disease, respectively. The results
      of HPV DNA testing varied depending on the cutoff value used to define a positive
      result. At the standard cutoff level (RLU > 1x positive control), 16.2% of women
      screened were classified as high risk HPV DNA positive, as were 63 women with
      high grade disease (73%). CONCLUSIONS: DVI and HPV DNA testing identified similar
      numbers of high grade SIL (cervical intraepithelial neoplasia Grade 2,3) and
      invasive carcinoma cases as Pap smears. However, both classify considerably more
      women without cervical disease as being test positive.

PMID- 10951348
TI  - Prostate specific antigen adjusted for transition zone volume: the most powerful
      method for detecting prostate carcinoma.
AB  - BACKGROUND: Several methods for the identification of patients with prostate
      carcinoma have been proposed to enhance the clinical usefulness of prostate
      specific antigen (PSA). However, it remains unclear which method is superior in
      practical use. The authors attempted prospectively to identify the most powerful
      method with which to detect prostate carcinoma, especially among patients with
      intermediate PSA levels. METHODS: Between October 1997 and August 1999,
      systematic sextant biopsies were performed on 281 patients, including 147 with
      PSA levels between 4.1 ng/mL and 10.0 ng/mL. The clinical values of PSA, the free
      PSA to total PSA ratio (free/total PSA ratio), alpha-1-antichymotrypsin-PSA
      complex (PSA-ACT), the calculated derivatives, PSA density (PSAD), and PSA
      density of the transition zone (PSATZD) for the detection of prostate carcinoma
      were compared by using receiver operating characteristic (ROC) curves and
      logistic regression analyses. RESULTS: According to ROC curve analysis, PSATZD
      had the greatest area under the curve in the overall patient population and in
      patients with intermediate PSA levels. In patients with intermediate PSA levels,
      at the sensitivity of 90%, PSATZD would have prevented unnecessary biopsies in 68
      of 117 patients who were without prostate carcinoma, whereas PSA, free/total PSA
      ratio, and PSA-ACT would have prevented unnecessary biopsies in 25, 28, and 25
      patients, respectively. Stepwise logistic regression analysis showed that PSATZD
      and findings on digital rectal examination were significant independent
      predictors. CONCLUSIONS: PSATZD had the most useful validity in the
      differentiation between prostate carcinoma and benign prostatic enlargement in
      the overall patient population and in patients with intermediate PSA levels.

PMID- 10951350
TI  - Is thyroidectomy necessary in RET mutations carriers of the familial medullary
      thyroid carcinoma syndrome?
AB  - BACKGROUND: The results and consequences of genetic testing in a family with
      familial medullary thyroid carcinoma (FMTC) are described. METHODS: In the
      screening of relatives, serum calcitonin is replaced by RET mutation analysis
      that was performed in families suspected of hereditary medullary thyroid
      carcinoma (MTC). In 4 of 10 families, mutation in exon 10 was found in codon 611.
      RESULTS: One hundred fifty persons belonging to 30 families were tested, of which
      10 families were carriers of RET mutation in exon 10. In 1 of these families with
      MTC only, 2 brothers were gene carriers of a RET codon 611 mutation and lived
      without any sign of MTC. One is aged 79 years, and the other died at the age of
      71 of other causes. CONCLUSIONS: The results indicate that the gene carrier in
      families with MTC without other endocrine tumors (FMTC) exhibits a highly
      variable disease course. A 611 codon mutation is most often a rather mild and
      slow progression form of MTC. Because 2 gene carriers were still alive at age 70
      years without showing any sign of the disease, it is tempting to ask if all gene
      carriers with a 611 codon mutation without other endocrine tumors should be
      operated on, and if so, at what age? In the authors' opinion, more information is
      needed to be able to answer these questions. The current guidelines for treatment
      of patients with hereditary MTC are discussed.

PMID- 10951349
TI  - Identification of transforming growth factor-beta1-binding protein overexpression
      in carmustine-resistant glioma cells by MRNA differential display.
AB  - BACKGROUND: The authors previously demonstrated the presence of cells in primary
      human malignant gliomas that intrinsically are resistant to carmustine (BCNU).
      Numerous studies have identified mechanisms of therapy resistance in these cells;
      however, the authors' work and that of others suggest that additional mechanisms
      of resistance exist. METHODS: The authors identified a glioma cell line that
      lacks detectable methylguanine methyltransferase expression and does not alter
      its expression of glutathione-S-transferase-pi in response to BCNU chemotherapy.
      This cell line was used in mRNA differential display experiments to identify
      genes involved in what to the authors' knowledge were previously undescribed
      mechanisms of resistance. RESULTS: The overexpression of the gene encoding the
      transforming growth factor latency binding protein was demonstrated in glioma
      cells selected for resistance to BCNU, compared with their parental unselected
      cells. CONCLUSIONS: Transforming growth factor-beta1 has pleiotropic functions in
      transformed and normal cells. Although activation of TGF-beta1 does not appear to
      be a causative factor in BCNU resistance in the current study, it may be involved
      in the growth of these resistant cells.

PMID- 10951351
TI  - Prognostic factors in head and neck soft tissue sarcomas.
AB  - BACKGROUND: Soft tissue sarcomas of head and neck constitute a heterogeneous
      group of rare malignant tumors occurring at rare sites. The purpose of this
      retrospective study is to evaluate the pathologic features, treatment modalities,
      outcome, patterns of failure, survival, and other prognostic factors. METHODS:
      The medical records of 72 patients whose tumors were diagnosed as head and neck
      sarcomas, treated at Tata Memorial Center between 1981 to 1995 were reviewed.
      Potential prognostic factors including age, gender, tumor size, histology, grade,
      and adjuvant treatment were evaluated. RESULTS: The overall and disease free
      survival at 5 years was 60% and 45%, respectively. The median survival and follow
      up was 76 and 38 months, respectively. Thirty-two patients (44.4%) developed
      recurrence of which 13 patients were salvaged. The univariate and multivariate
      analysis showed tumor size and grade as important prognostic factors for the
      survival. CONCLUSIONS: Tumor size greater than 5 cm and high grade tumors were
      important prognostic factors for survival. Every effort should be made for early
      diagnosis and wide surgical excision. For localized recurrent tumors without
      evidence of distant metastasis, surgery should be attempted whenever possible.
      High rates of locoregional failure in head and neck area indicate the need for
      improved treatment strategies.

PMID- 10951352
TI  - Use of complementary and alternative medicine by cancer patients is not
      associated with perceived distress or poor compliance with standard treatment but
      with active coping behavior: a survey.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is often used by cancer
      patients. Data on characteristics of users, concomitant psychologic disturbance,
      and compliance with standard treatment continue to be controversial. Use of and
      interest in CAM and their correlation with psychologic disturbance, ways of
      coping with illness, and compliance with standard treatment were examined in this
      study. METHODS: The authors conducted a survey in a consecutive sample of 205
      cancer patients undergoing radiotherapy, using a structured questionnaire to
      record use of and interest in CAM, the Hospital Anxiety and Depression Scale, the
      Hornheide Questionnaire to assess patient distress and social support, and the
      Freiburg Questionnaire of Coping with Illness. RESULTS: Of the 172 participants,
      24.4% (response rate, 83.9%) reported use of CAM, and 31.4% reported not having
      used but being interested in such methods. Logistic regression analysis including
      clinical, demographic, and psychologic characteristics as independent variables
      yielded 3 predictors of use of or interest in CAM: younger age (P = 0.004; odds
      ratio (OR), 0.96), progressive cancer (P = 0.064; OR, 1.47), and active coping
      behavior (P = 0.016; OR, 1.65). Patients interested in or using CAM did not show
      more psychologic disturbance, poorer social support, or less trust in medicine or
      compliance with radiotherapy than subjects without such interest. CONCLUSIONS:
      Use of CAM by cancer patients is not associated with perceived distress or poor
      compliance with medical treatment but with active coping behavior. Patients seem
      to consider CAM as supplementary to standard medical methods and one way of
      avoiding passivity and of coping with feelings of hopelessness.

PMID- 10951353
TI  - Tobacco interventions by oncology nurses in clinical practice: report from a
      national survey.
AB  - BACKGROUND: Tobacco use is an important risk factor in cancer, cancer recurrence,
      and increased treatment morbidity, but limited information is available about
      interventions for tobacco cessation used in oncology clinical practice. In 1996,
      the Agency for Health Care Policy Research (AHCPR) published the first evidence
      based smoking cessation guideline for use by health professionals. Using the
      AHCPR guideline as a framework, the authors describe the frequency of tobacco
      interventions provided by oncology nurses. METHODS: A questionnaire was mailed to
      4000 randomly selected members of the Oncology Nursing Society in winter of 1998.
      Of those who were mailed questionnaires, 1508 respondents (38%) were available
      for analysis. RESULTS: The typical respondent was female, 44 years of age, and
      had practiced as an oncology nurse for 12 years. Seven percent were current
      smokers, and 30% were former smokers. Most (86%) encountered smokers on a weekly
      basis, but only 10% had heard of the AHCPR guideline. The majority (64%) assessed
      and documented tobacco status, 38% assessed readiness to quit. Few went on to
      provide interventions: 36% provided counseling, 32% provided cessation advice,
      24% recommended nicotine replacement, and 16% taught skills to prevent relapse.
      Common barriers included perceived lack of patient motivation (74%) and the
      nurse's lack of time (52%) and skills (53%). The majority stated that they wanted
      to help patients stop smoking (88%) but needed additional training (92%).
      CONCLUSIONS: Documentation of tobacco status alone is not adequate in assisting
      patients with smoking cessation. Greater efforts are needed to educate oncology
      nurses about the range of tobacco interventions available and to facilitate their
      use in clinical settings.

PMID- 10951354
TI  - Fatal liver failure after the administration of raltitrexed for cancer
      chemotherapy: a report of two cases.
AB  - BACKGROUND: Acute fatal liver failure is a relatively rare event after the
      administration of antineoplastic drugs. To the authors' knowledge, there have
      been no published reports of this phenomenon after the administration of the
      widely applied cytotoxic agent raltitrexed. METHODS: The authors present two
      cases of fulminant fatal liver failure that occurred after the administration of
      raltitrexed as anticancer chemotherapy. RESULTS: A female patient age 76 years
      and a male patient age 56 years were given raltitrexed as adjuvant treatment of
      colorectal carcinoma and as palliative therapy for advanced biliary carcinoma,
      respectively. Although the initial cycles of chemotherapy were uneventful, both
      patients developed fulminant liver failure with rapid deterioration of their
      condition after the second and sixth cycles of chemotherapy, respectively, and
      both died within 24 hours despite immediate hospitalization. Histologic
      evaluation of liver samples taken during autopsy showed signs of acute necrosis
      involving roughly 50% of the liver without signs of subacute liver toxicity.
      CONCLUSIONS: To the authors' knowledge the current study is the first to
      demonstrate fatal liver toxicity after chemotherapy with the thymidylate synthase
      inhibitor raltitrexed. Clinicians should be aware of the potential acute fatal
      side effect of this otherwise well tolerated and widely used cytotoxic agent.

PMID- 10951355
TI  - Toward a comparison of survival in American and European cancer patients.
AB  - BACKGROUND: Only recently have extensive population-based cancer survival data
      become available in Europe, providing an opportunity to compare survival in
      Europe and the United States. METHODS: The authors considered 12 cancers: lung,
      breast, stomach, colon, rectum, melanoma, cervix uteri, corpus uteri, ovary,
      prostate, Hodgkin disease, and non-Hodgkin lymphoma. The authors analyzed 738,076
      European and 282,398 U.S. patients, whose disease was diagnosed in 1985-1989,
      obtained from 41 EUROCARE cancer registries in 17 countries and 9 U.S. SEER
      registries. Relative survival was estimated to correct for competing causes of
      mortality. RESULTS: Europeans had significantly lower survival rates than U.S.
      patients for most cancers. Differences in 5-year relative survival rates were
      higher for prostate (56% vs. 81%), skin melanoma (76% vs. 86%), colon (47% vs.
      60%), rectum (43% vs. 57%), breast (73% vs. 82%), and corpus uteri (73% vs. 83%).
      Survival declined with increasing age at diagnosis for most cancers in both the
      U.S. and Europe but was more marked in Europe. CONCLUSIONS: Survival for most
      major cancers was worse in Europe than the U.S. especially for older patients.
      Differences in data collection, analysis, and quality apparently had only
      marginal influences on survival rate differences. Further research is required to
      clarify the reasons for the survival rate differences.

PMID- 10951356
TI  - Associations between community income and cancer incidence in Canada and the
      United States.
AB  - BACKGROUND: Associations between socioeconomic status (SES) and the incidence of
      cancer have been reported previously in the U.S. Canada has more comprehensive
      health care and social programs than the U.S. The purpose of this study was to
      compare the strength of associations between SES and cancer incidence in Canada
      and the U.S. METHODS: The regions studied were the Canadian province of Ontario
      and the areas of the U.S. covered by the Surveillance, Epidemiology, and End
      Results (SEER) program. The populations at risk were defined using the 1991
      Canadian Census and the 1990 U.S. Census. The populations of Ontario and of the
      SEER areas of the U.S. were each divided into deciles on the basis of median
      household income. Population-based cancer registries were used to identify
      incident cases. Age-standardized incidence rates for all major groups of
      malignant diseases were calculated for each SES decile in Ontario and in the U.S.
      Income-associated incidence gradients observed in Ontario and the U.S. were
      compared. RESULTS: The incidence of most types of cancer was similar in Ontario
      and the U.S. In both countries, there were moderately strong, inverse
      associations between income level and the incidence of carcinomas of the cervix,
      the head and neck region, the lung, and the gastrointestinal tract. In both
      Ontario and the U.S., several of these diseases were twice as common in the
      bottom income decile than they were in the top decile. In contrast, carcinoma of
      the female breast and carcinoma of the prostate were more common among higher
      income communities in both countries, but the observed associations were weaker
      in Ontario. CONCLUSIONS: Despite Canada's universal health insurance and more
      comprehensive social security system, the association between lower socioeconomic
      status and the incidence of many common cancers is just as strong in Ontario as
      it is in the U.S. The mechanisms responsible for these associations require
      further investigation.

PMID- 10951357
TI  - Frequency of central nervous system involvement in primary cutaneous B-cell
      lymphoma.
AB  - BACKGROUND: Primary cutaneous B-cell lymphoma (CBCL) constitutes approximately
      20% of all primary cutaneous lymphomas. Apart from primary cutaneous large B-cell
      lymphoma presenting on the legs (PCLBCL-leg), primary CBCLs run an indolent
      clinical course, rarely disseminate to extracutaneous sites, and have an
      excellent prognosis. Because of recent observations in two patients who developed
      central nervous system (CNS) involvement, follow-up data of all primary CBCL
      patients registered at the Dutch Cutaneous Lymphoma Group between 1985 and 1998
      were investigated for evidence of CNS involvement. METHODS: Follow-up data from
      160 primary CBCLs were evaluated. This group included 122 primary cutaneous
      follicle center cell lymphomas (PCFCCLs), 16 primary cutaneous immunocytomas or
      marginal zone B-cell lymphomas, and 22 PCLBCL-leg. RESULTS: Of all 160 patients
      with primary CBCLs, 11 died of lymphoma, including 4 of 122 patients (3%) with
      PCFCCL and 7 of 22 patients (32%) with PCLBCL-leg. Four of these 11 patients,
      including 3 with PCFCCL and 1 with PCLBCL-leg, had developed CNS involvement 3-93
      months (median, 30 months) after diagnosis. All patients died 1-9 months (median,
      7 months) after the development of CNS involvement. In the group of 122 patients
      with PCFCCL, CNS involvement occurred in 3 of 7 patients (43%) who developed
      extracutaneous disease and accounted for 3 of 4 lymphoma-related deaths (75%).
      CONCLUSIONS: The results of this study indicate that approximately 2% of all
      primary CBCLs may develop CNS involvement. Whereas, in rare PCFCCL patients,
      developing extracutaneous disease CNS involvement was an important cause of
      death, patients with PCLBCL-leg and secondary CBCL died more frequently due to
      involvement of non-CNS organ systems.

PMID- 10951358
TI  - Outcome of cancer pain consultations.
AB  - BACKGROUND: All major cancer centers in the United States are equipped with pain
      management consultation services. We report on the outcome of such consultations
      within 24 hours from the intervention. METHODS: All consecutive patients referred
      to the pain management service of a tertiary care cancer center were assessed
      before and 14-24 hours after the intervention. RESULTS: A total of 45 patients
      completed the study. The mean current pain intensity score was 5.2 on the Visual
      Analogue Scale before the consultation and 2.7 after the consultation (P < 0.05).
      The pain was described as excruciating on the Categorical Scale by three patients
      before the consultation and by no patients after the consultation. CONCLUSIONS:
      In hospitalized cancer patients with difficult to control pain, cancer pain
      consultations result in a measurable effect within 24 hours of the pharmacologic
      intervention. To avoid unnecessary suffering, timeliness is of the utmost
      importance when requesting and delivering cancer pain consultations.

PMID- 10951359
TI  - Evidence for hypomethylation in two children with acute lymphoblastic leukemia
      and leukoencephalopathy.
AB  - BACKGROUND: The prognosis of patients with acute lymphoblastic leukemia (ALL) in
      childhood has improved with intensive chemotherapy. In particular, central
      nervous system (CNS) leukemia has been well controlled by the presymptomatic
      administration of intrathecal methotrexate (MTX), high dose systemic MTX, and
      irradiation. However, the prolonged intrathecal administration and/or the
      administration of high doses of systemic MTX, especially when combined with
      irradiation, can lead to leukoencephalopathy (LE), a serious CNS complication of
      such prophylaxis. Because the mechanisms by which MTX causes this complication
      have not been elucidated, the authors investigated the transmethylation status of
      the cerebrospinal fluid (CSF) in two children with ALL and LE to investigate the
      pathophysiology of that disorder. METHODS: The levels of S-adenosylmethionine
      (SAM) and S-adenosylhomocysteine (SAH) were measured in the CSF of 2 children
      with ALL and LE, 7 children with ALL only who were undergoing presymptomatic
      administration of MTX, and 18 reference children in whom diagnostic lumbar
      puncture was indicated for other reasons. A sensitive, high performance liquid
      chromatography (HPLC) method was used with fluorescence detection. RESULTS: The
      concentrations of SAM in the CSF were lower in the patients with ALL during
      treatment with MTX compared with the reference children. The SAM levels in the 2
      patients with both ALL and LE were slightly lower than the levels in the 7
      patients with ALL only. The SAH concentrations in the CSF were higher in the
      patients with ALL and LE compared with the patients with ALL only and the
      reference children. The mean concentration of SAH in the CSF was similar in the
      reference children to that found in the 7 patients with ALL only. The SAM-to-SAH
      ratios were lower in the 2 patients with ALL and LE and in the 7 patients with
      ALL only compared with the reference children. The ratios in the patients with
      ALL and LE were still lower than in those with ALL only, thus providing
      supporting evidence of hypomethylation in the 2 patients with ALL and LE.
      CONCLUSIONS: The data suggest that the treatment of children with ALL using MTX
      causes subclinical hypomethylation and that progressive hypomethylation in the
      CNS, as evidenced in the 2 patients with ALL and LE, may be responsible for the
      demyelination in the LE induced by MTX.

PMID- 10951360
TI  - DNA ploidy analysis and cell proliferation in congenital sacrococcygeal
      teratomas.
AB  - BACKGROUND: Congenital sacrococcygeal teratoma is the most common germ cell tumor
      in infants and children. It usually is diagnosed at birth, is benign, and
      consists of fully differentiated mature tissues. Congenital sacrococcygeal
      teratomas (SCTs) also may contain immature tissues, most commonly of neural
      origin. The proportion of malignant teratomas increases with advancing age, but
      the relation between mature and immature SCTs is not well understood. Thus, it is
      very important to determine proliferative activity, DNA ploidy, and DNA index to
      predict biologic behavior of these tumors. METHODS: DNA ploidy and cell
      proliferation were analyzed by flow cytometry, and the expression of
      proliferating cell nuclear antigen (PCNA) and Ki-67 were analyzed
      immunohistochemically on paraffin embedded tissue. RESULTS: All the tumors that
      were surgically treated within 3 months after birth, including immature teratoma,
      were diploid. Strongly positive PCNA immunostaining was found in both immature
      teratomas, and weakly positive PCNA was found in nine cases. Weak positivity for
      Ki-67 was observed in 2 cases, and moderate positivity was observed in 6 cases
      including immature teratomas. CONCLUSION: The value of flow cytometry in the
      prediction of biologic behavior of congenital SCT should be analyzed further. Our
      results suggest that Ki-67 and especially PCNA may reflect the proliferative
      activity of these tumors.

PMID- 10951361
TI  - The effect of polyethylene particle chemistry on human monocyte-macrophage
      function in vitro.
AB  - Osteolysis remains the most important problem in orthopedic implant failure. Wear
      debris from the implant contains polyethylene (PE) particulate which has been
      shown to activate monocyte-derived macrophages (MDM). Although the response of
      MDM has been shown to be influenced by the size, shape, and chemical type of PE,
      the effect of chemically altered PE on MDM has not been studied. In this study,
      human MDM were seeded onto glass coverslips coated with virgin high density
      (HD)PE and chemically modified HDPE (impregnated with ppm levels of CoCl(2) and
      oxidized by heat) mixed with type I collagen and cultured for 96 h. Light
      microscopic evaluation demonstrated consistent phagocytosis of the HDPE
      particulate that was confirmed by scanning electron and transmission electron
      microscopy with little evidence of cytotoxicity. Evaluation of pro-inflammatory
      mediator secretion by MDMs in response to the virgin and chemically modified HDPE
      revealed significant differences in interleukin (IL)-1, tumor necrosis factor
      (TNF)-alpha, and IL-6 secretion. A significant elevation of IL-1 secretion was
      observed after initial exposure to virgin HDPE particles compared with controls
      (p = 0.001). IL-1 secretion was also elevated in the low oxidized particle groups
      (p = 0.001), whereas the highly oxidized particles were not different than
      controls. Secretion of both IL-6 (p = 0.03) and TNF-alpha (p = 0.007) were
      significantly elevated by the low oxidized HDPE particles whereas the virgin and
      highly oxidized groups showed no difference. The different effects on MDM
      activation when HDPE surface chemistry was altered, highlight the importance of
      defining the particle properties when studying the role of MDM activation in in
      vitro systems and extrapolating these observations to the in vivo situation.

PMID- 10951362
TI  - Gelatin-based resorbable sponge as a carrier matrix for human mesenchymal stem
      cells in cartilage regeneration therapy.
AB  - Adult mesenchymal stem cells (MSCs), found in the bone marrow, have the potential
      to differentiate into multiple connective tissue types, including cartilage. In
      this study, we examined the potential of a porous gelatin sponge, Gelfoam, for
      use as a delivery vehicle for MSCs in cartilage regeneration therapy. Adult human
      MSCs (hMSCs) were seeded throughout the gelatin sponge after a 2-h incubation
      period. When cultured for 21 days in vitro in a defined medium supplemented with
      10 ng/mL of TGF-beta 3, hMSC/Gelfoam constructs produced a cartilage-like
      extracellular matrix containing sulfated glycosaminoglycans (s-GAGs) and type-II
      collagen, as evident upon histologic evaluation. Constructs loaded with a cell
      suspension of 12 x 10(6) cells/mL produced an extracellular matrix containing 21
      microg of s-GAG/microg of DNA after 21 days of culture. This production was more
      efficient than constructs loaded at higher or lower cell densities, indicating
      that the initial seeding density influences the ability of cells to produce
      extracellular matrix. When implanted in an osteochondral defect in the rabbit
      femoral condyle, Gelfoam cylinders were observed to be very biocompatible, with
      no evidence of immune response or lymphocytic infiltration at the site. Based on
      these observations we conclude that Gelfoam resorbable gelatin sponge is a
      promising candidate as a carrier matrix for MSC-based cartilage regeneration
      therapies.

PMID- 10951363
TI  - 3-D AE visualization of bone-cement fatigue locations.
AB  - This study addresses the visualization of crack locations in bone-cement material
      using a three-dimensional acoustic emission source location technique. Computer
      software based on an earthquake location technique was developed to determine AE
      source locations and was used to investigate material cracks formed at the tip of
      a notch in bone cement. The computed locations show that the cracks form linear
      features with dimensions between 0.1 and 0.2 mm although larger linear features
      (almost 3.5 mm) also are present. There is a difference of about 2.5 mm between
      the average of the event locations, and the location of the tip of the notch is
      2.5 mm, which may be due to the finite size of the sensors (5 mm in diameter).

PMID- 10951364
TI  - Adhesion and proliferation of corneal epithelial cells on self-assembled
      monolayers.
AB  - The effect of surface chemistry on the proliferation and adhesion of SV-40 human
      corneal epithelial cells was investigated. The surface chemistry of substrates
      was controlled by the deposition of self-assembled monolayers (SAMs) terminated
      with the following functional groups: -CF3, -CH3, -CO(2)H, and -NH(2). SAMs of
      alkanethiols on gold and of alkylsiloxanes on SiOx were included in the study.
      Comparisons are made between different types and functionalities of SAMs and
      between SAM-covered substrates and tissue culture polystyrene. Adhesion assays
      were performed after incubation of the cells for 1 h in 10% fetal bovine serum
      and in serum-free conditions. The cellular response was found to be a function of
      surface chemistry and the presence of exogenous proteins. The number of cells
      that adhered to most of the SAMs in 10% serum and in serum-free conditions was
      not significantly different from the number of cells that adhered to TCPS.
      Proliferation assays were carried out in 10% serum and in 0.5% serum. Cell
      behavior was influenced by surface chemistry but did not deviate significantly
      from the behavior on TCPS for most of the SAMs. Serum level did not play a major
      role in cell proliferation. Our data establish the expected behaviors for a
      corneal epithelial cell line under defined conditions on specific surfaces.

PMID- 10951366
TI  - Characterization of osteoblast-like behavior of cultured bone marrow stromal
      cells on various polymer surfaces.
AB  - The creation of novel bone substitutes requires a detailed understanding of the
      interaction between cells and materials. This study was designed to test certain
      polymers, specifically poly(caprolactone) (PCL), poly(D,L-lactic-CO-glycolic
      acid) (PLGA), and combinations of these polymers for their ability to support
      bone marrow stromal cell proliferation and differentiation. Bone marrow stromal
      cells were cultured from New Zealand White rabbits and were seeded onto glass
      slides coated with a thin layer of PCL, PLGA, and combinations of these two
      polymers in both a 40:60 and a 10:90 ratio. Growth curves were compared. At the
      end of 2 weeks, the cells were stained for both matrix mineralization and
      alkaline phosphatase activity. There was no statistically significant difference
      in growth rate of the cells on any polymer or polymer combination. However, there
      was a striking difference in Von Kossa staining and alkaline phosphatase
      staining. Cells on PCL did not show Von Kossa staining or alkaline phosphatase
      staining. However, in the 40:60 and 10:90 blends, there was both positive Von
      Kossa and alkaline phosphatase staining. These data indicate that PCL alone may
      not be a satisfactory material for the creation of a bone substitute. However, it
      may be used in combination with PLGA for the creation of a bone substitute
      material.

PMID- 10951365
TI  - Calcium and phosphate supplementation promotes bone cell mineralization:
      implications for hydroxyapatite (HA)-enhanced bone formation.
AB  - Organic phosphate, in particular beta-glycerophosphate (beta-GP), has been used
      to induce mineralization in cell culture systems. It serves as a source of
      inorganic phosphate when hydrolyzed by alkaline phosphatase. This study examined
      the effect of supplemental calcium and phosphate as well as the influence of
      various metabolic inhibitors on mineralization in a rat osteoblast-like cell
      culture system. Mineralization was induced by supplementation of 1.8 mM of Ca(+2)
      and 5 mM of beta-GP or Pi. Mineral deposits associated with in vitro
      mineralization were revealed under SEM and TEM. Levamisole (10-100 microM)
      inhibited alkaline phosphatase activity and effectively reduced mineral
      formation. Actinomycin (500 ng/mL) and cycloheximide (50 microg/mL) also reduced
      mineral depositions by blocking RNA synthesis and protein synthesis,
      respectively. Levamisole and beta-GP did not appear to influence DNA synthesis.
      Spontaneous precipitation of calcium phosphate mineral was not detected in the
      culture medium with calcium and phosphate supplements in the absence of cell
      culture. The findings suggest that an elevated concentration of calcium and
      phosphate is crucial for in vitro mineralization. Furthermore, the mineralization
      process is associated with biologic events rather than with a spontaneous
      precipitation of calcium phosphate mineral. In view of the degradation potential
      of hydroxyapatite (HA)-coated implants, these results may be a viable indication
      that HA enhances bone formation through a similar mechanism.

PMID- 10951367
TI  - Studies on nerve cell affinity of chitosan-derived materials.
AB  - Reparation of the central nervous system (CNS) is important because when it is
      impaired its recovery is difficult and concomitant malfunction of other parts of
      body occurs. In our previous studies, chitosan was found to be a good material
      supporting nerve repair. The purpose of this article was to study the ability of
      chitosan and some chitosan-derived materials to facilitate the growth of nerve
      cells. Those materials were chitosan, glutaraldehyde-crosslinked chitosan,
      glutaraldehyde-crosslinked chitosan-gelatin conjugate, a chitosan-gelatin
      mixture, chitosan coated with polylysine (CAP), and a chitosan-polylysine mixture
      (CPL). Gelatin and polylysine were used as controls. After nerve cells
      (gliosarcoma cells and normal cerebral cells) were grown on those materials,
      their attachment, spread, and growth were observed. The adsorption of some
      extracellular matrix molecules such as laminin and fibronectin on the materials
      and the role the molecules play in nerve cell attachment and spreading were also
      studied by enzyme-linked immunosorbent assay and MTT method. We found that both
      CAP and CPL have excellent nerve cell affinity, defined as the ability to promote
      nerve cell to grow and function normally. Those two materials may be promising
      for the repair of the nervous system. Materials precoated with laminin,
      fibronectin, and serum were analyzed for their nerve cell affinity. Results
      suggest that after being precoated with laminin and fibronectin solution or
      serum, all material have better nerve cell affinity.

PMID- 10951368
TI  - Evaluation of the response of primary human peripheral blood mononuclear
      phagocytes to challenge with in vitro generated clinically relevant UHMWPE
      particles of known size and dose.
AB  - The response of primary human peripheral blood mononuclear phagocytes to
      challenge with clinically relevant ultra-high molecular weight polyethylene
      (UHMWPE) wear debris of known particle size and dose was evaluated. Particles
      with a mean size of 0.24, 0. 45, 1.7, 7.6, and 88 microm were cocultured with
      cells for 24 h before assessment of cell viability and production of the
      osteolytic cytokines interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha,
      and granulocyte macrophage colony-stimulating factor, and prostaglandin E(2). All
      particle fractions were evaluated at particle volume (microm(3)) to cell number
      ratios of 10:1 and 100:1, which had been previously identified as being the most
      stimulatory and clinically relevant. None of the test fractions had an effect on
      cell viability. Whereas the heterogeneity of human individuals was clearly
      evident in the responses of the donors evaluated in this study (the response of
      donor 3 was between 5 and 20 times greater than the other donors), the most
      biologically active particles were found to be submicrometer in size. Stimulation
      with phagocytosable particles (0.24, 0.45, and 1.7 microm) resulted in enhanced
      levels of cytokine secretion. Macrophages stimulated with particles outside this
      size range produced considerably less cytokines at the volumes tested. These
      results confirm earlier findings and suggest that the size and volume of UHMWPE
      particles are critical factors in macrophage activation. Furthermore, they
      suggest that the heterogeneity of human individuals may be another important
      factor in determining implant life.

PMID- 10951369
TI  - Influence of isostatic compression on the stability of vancomycin loaded with a
      calcium phosphate-implantable drug delivery device.
AB  - It is essential to prevent microbial infections after osteoarticular trauma or
      prosthesis implantation. As an alternative to antibiotic parenteral
      administration, antibiotic-loaded biomaterials allow high concentrations to be
      obtained in situ without systemic toxicity. Although the formulation of biphasic
      calcium-phosphate (BCP)-vancomycin granules by isostatic compression has recently
      been used to produce drug-delivery devices, the stability of vancomycin needs to
      be proven. In this study, vancomycin was associated with BCP powders by isostatic
      compression at 100, 140, or 200 MPa and then extracted or released by a rotating
      paddle system for 24 h. Vancomycin assays were performed by spectrophotometric
      and microbiological methods. The results show that all vancomycin associated with
      the material was recovered after extraction without degradation. Thus, vancomycin
      was not denaturated after application of 100, 140, or 200 MPa of isostatic
      compression. The results for vancomycin released from granules compressed at the
      three pressures were not significantly different (p =.01) whether assays were
      performed microbiologically or spectrophotometrically, indicating a good
      correlation between the two methods. This process involving high pressure appears
      to be a good means of developing drug delivery devices loaded with therapeutic
      agents without denaturating the components.

PMID- 10951370
TI  - Quantifying the adherence of fibroblasts to titanium and its enhancement by
      substrate-attached material.
AB  - Normal human skin fibroblasts were cultured on tissue culture polystyrene and on
      commercially pure titanium. In addition, substrate-attached material that
      remained on the surfaces after detachment of fibroblasts with a chelating agent
      was examined. The force required to detach 50% of the fibroblasts from each
      substrate was assessed by centrifugation. The results showed a time-dependent
      decrease in the force required to detach fibroblasts from titanium not seen on
      tissue culture polystyrene. Nearly all cells detached from the titanium surfaces
      at 7.85 x 10(x3) dynes/cell after 3 or 5 days in culture, whereas few cells
      detached from tissue culture polystyrene. Cells freshly seeded onto titanium
      substrates that had been coated with substrate-attached material by prior culture
      of fibroblasts for 3 or 5 days showed an approximately sixfold increased
      adherence. The results of immunofluorescence staining for fibronectin and its
      receptor suggest that the nature of the interaction between this extracellular
      matrix ligand and the substrate may be important in determining cellular
      stiffness at the cell-extracellular matrix interface.

PMID- 10951371
TI  - Increased corrosion resistance of stent materials by converting current surface
      film of polycrystalline oxide into amorphous oxide.
AB  - Current efforts of new stent technology have been aimed largely at the
      improvement of intravascular stent biocompatibility. Among the chemical
      characteristics of metallic stents, surface oxide corrosion properties are
      paramount. Using our unique technique, the currently marketed 316 L stainless
      steel and nitinol stent wires covered with polycrystalline oxide were chemically
      etched and then passivated to form amorphous oxide. Excellent metallic-stent
      corrosion resistance with an amorphous oxide surface was demonstrated in our
      previous in vitro study. For in vivo validation, we compared the corrosion
      behavior of different oxide surfaces on various forms of test wires in the
      abdominal aorta of mongrel dogs using open-circuit potential and cyclic anodic
      polarization measurements. After conduction, the retrieved test wires were
      observed under scanning electron microscope. No passivity breakdown was found for
      wires covered with amorphous oxide, while wires with polycrystalline oxide showed
      breakdown at potentials between +0.2 to + 0.6 V. It has been proven that severe
      pitting or crevice corrosion occurred on the surface of polycrystalline oxide,
      while the surface of amorphous oxide was free of degradations in our experiment.
      We have demonstrated that this amorphous oxide coating on metallic material
      provides better corrosion resistance, not only in vitro but also in vivo, and it
      is superior not only in strength safety but also in medical device
      biocompatibility.

PMID- 10951372
TI  - Preparation of graded porous titanium coatings on titanium implant materials by
      plasma spraying.
AB  - Graded porous titanium coatings have been deposited on titanium substrates for
      dental implants by plasma spraying in an argon atmosphere. X-ray diffraction
      (XRD), scanning electron microscopy (SEM), surface roughness measurement, and
      tensile strength tests were performed on graded porous coatings. The results
      showed that Ti(3)O(5) was formed in the outermost surface of the porous coatings
      due to oxidation. The graded porous coatings consisted of three layers. The outer
      layer was full of macropores with a surface roughness of approximately 100
      microm. The diameter of many macropores reached and even surpassed 150 microm,
      which could be beneficial for tissue to grow into the coating. The middle layer
      consisted of a mixture of micropores and macropores. The inner layer was a very
      dense and tight interface layer that included mechanical, physical, and
      metallurgical bonding. In tensile strength tests, testing bars peeled off the
      coatings, because the adhesive agent fractured, but the coatings remained intact.

PMID- 10951373
TI  - Cytotoxic effect of bone cements in HL-60 cells: distinction between apoptosis
      and necrosis.
AB  - Ten PMMA-based bone cements used in prosthetic surgery have been studied with
      respect to the induction of programmed cell death (i.e., apoptosis) in HL-60
      cells, which are remarkably sensitive to various apoptotic stimuli. Annexin V
      binding and propidium iodide (PI) exclusion were the methods for detection of
      early apoptotic changes, while PI entry was considered as a marker of necrosis.
      Hoechst 33342 staining was used to detect DNA fragmentation and Alamar blue was
      applied to measure oxide-reduction activity of cells. The production of reactive
      oxygen species (ROS) related to cell damage was verified using
      dichlorofluorescein-diacetate (DCFH-DA) oxidation to DCF. Under our experimental
      conditions, the cements tested, for the most part, were not toxic to leukemic
      cells at 4 and 24 h. After 24 h, three cements were able to induce cell death,
      with two eliciting both apoptosis and necrosis, and one cement acting mainly via
      apoptosis. Both processes of cell death are likely to be mediated by the
      production of oxygen-free radicals. These findings provide potential leads for
      investigation into the molecular mechanisms of cell death, which are responsible
      for tissue damage by cements and intolerance of cemented prostheses.

PMID- 10951374
TI  - Microfabricated elastomeric stencils for micropatterning cell cultures.
AB  - Here we present an inexpensive method to fabricate microscopic cellular cultures,
      which does not require any surface modification of the substrate prior to cell
      seeding. The method utilizes a reusable elastomeric stencil (i.e., a membrane
      containing thru holes) which seals spontaneously against the surface. The stencil
      is applied to the cell-culture substrate before seeding. During seeding, the
      stencil prevents the substrate from being exposed to the cell suspension except
      on the hole areas. After cells are allowed to attach and the stencil is peeled
      off, cellular islands with a shape similar to the holes remain on the cell
      culture substrate. This solvent-free method can be combined with a wide range of
      substrates (including biocompatible polymers, homogeneous or nonplanar surfaces,
      microelectronic chips, and gels), biomolecules, and virtually any adherent cell
      type.

PMID- 10951375
TI  - Osteoinductivity and biomechanics of a porous ceramic with autogenic periosteum.
AB  - Twenty-one dogs were used to study the osteoinductivity and biomechanical
      properties of a biphasic porous ceramic with autogenic periosteum implanted in
      muscle. The ceramic implants were swathed in fresh periosteum derived from the
      same animals and implanted in the femur muscles. The other two groups of animals
      served as controls using the same material implanted in the femur bones and
      muscles without periosteum. Biomechanical measurements showed that, in the
      muscles, the experimental group had a higher bending strength than the unswathed
      group by the time the samples were harvested. Six months postoperatively, the
      strength of the samples in the experimental group had almost reached that of
      normal bones. The results of X-ray diffraction and infrared spectrometric
      analysis suggested that the degradation rate and speed of tricalcium phosphate
      (TCP) of the ceramic in the experimental group were faster than in the unswathed
      samples, but slower than in samples implanted in bones. The bone replacement and
      bone-inducing activity were excellent in the periosteum-swathed samples.
      Histologically, satisfactory bone repair was seen in the experimental samples.
      All results indicate that autogenic periosteum could increase bioactivity of
      ceramics in heterosites and improve bone formation in the surroundings of porous
      calcium phosphate ceramics. The data also infer that the complicated procedure of
      culturing bone growth factors with biomaterials in vitro to obtain bioactive
      grafts could be replaced by this relatively simple method.

PMID- 10951376
TI  - Effect of silver, copper, mercury, and nickel ions on cellular proliferation
      during extended, low-dose exposures.
AB  - Previous studies have demonstrated and quantified the cytotoxicity of metal ions
      in vitro, but the data from these reports have been limited to short-term
      exposures of metal ions to cells (24-72 h). Yet, the longer-term, low-dose
      effects of metal ions are most relevant to the clinical use of dental and other
      biomedical alloys. Thus, the purpose of the current study was to assess longer
      term effects of ions of silver, copper, mercury, and nickel - four metal ions
      known to be released from dental alloys - on monocytes. THP-1 human monocytes
      were exposed to the metal ions for up to 4 weeks. Concentrations of the metal
      ions were 1-10% of those known to cause cytotoxicity with 24-h exposures.
      Cellular proliferation and cellular viability were measured weekly. Ag(1+) and
      Hg(2+) did not alter the percentage of nonviable cells, but Cu(2+) and Ni(2+)
      increased the nonviable component as a function of metal concentration. These
      effects were cumulative over the 4 weeks only for Ni(2+). All metal ions caused a
      significant reduction in cellular proliferation, but the pattern of the effect
      was unique to each metal ion, and the effects were often not evident until 3 or 4
      weeks of exposure. The results of the current study indicate that metal ions
      released from metallic biomaterials may have adverse biological effects at
      concentrations lower than previously reported.

PMID- 10951377
TI  - Mechanical evaluation and design of a multilayered collagenous repair
      biomaterial.
AB  - One method of fabricating implantable biomaterials is to utilize biologically
      derived, chemically modified tissues to form constructs that are both
      biocompatible and remodelable. Rigorous mechanical characterization is a
      necessary component in material evaluation to ensure that the constructs will
      withstand in vivo loading. In this study we performed an in-depth biaxial
      mechanical and quantitative structural analysis of GraftPatch (GP), a biomaterial
      constructed by assembling chemically treated layers of porcine small intestinal
      submucosa (SIS). The mechanical behavior of GP was compared to both native SIS
      and to glutaraldehyde-treated bovine pericardium (GLBP) as a reference
      biomaterial. Under biaxial loading, GP was found to be stiffer than native SIS
      and mechanically anisotropic, with the preferred fiber direction demonstrating
      greater stiffness. Quantitative structural analysis using small-angle light
      scattering indicated a uniform fiber structure similar to GLBP and SIS. To enable
      test-protocol-independent quantitative comparisons, the biaxial mechanical data
      were fit to an orthotropic constitutive model, which indicated a similar degree
      of mechanical anisotropy between the three groups. We also demonstrate how the
      constitutive model can be used to design layered biocomposite materials that can
      undergo large deformations.

PMID- 10951378
TI  - Glutardialdehyde induced fluorescence technique (GIFT): a new method for the
      imaging of platelet adhesion on biomaterials.
AB  - One of the major limitations of biomaterials used in medicine is the adhesion and
      subsequent activation of platelets upon contact with blood. The development of
      new or modified materials necessitates adequate methods for the detection and
      quantification of platelet/material interactions. These interactions are commonly
      investigated by means of scanning electron microscopy (SEM), radioisotope and
      immunological techniques, or by quantification of released platelet contents.
      Given the lack of a simple, rapid, and inexpensive assay, we developed a novel
      method for the accurate assessment of platelet adhesion after contact with
      foreign surfaces, which enables quantitative measurements as well as imaging of
      the platelet shape change, and which omits conventional or immunological staining
      and time-consuming preparative steps. The glutardialdehyde induced fluorescence
      technique (GIFT) uses the epifluorescence of glutardialdehyde-fixed platelets
      detected by fluorescence microscopy and is suitable for opaque and transparent
      materials. Combined with computer-aided image analysis, numbers of adherent
      platelets, platelet-covered surface, and average platelet spread area can be
      determined as markers of surface thrombogenicity. To validate the technique, four
      materials of different thrombogenicity [polypropylene (PP), poly(D,L-lactide)
      (PDLLA), 2-hydroxyethyl-methacrylate-grafted PDLLA (PDLLA-HEMA), and heparin
      coupled PDLLA-HEMA] were investigated by GIFT and SEM. We found concordant
      results with SEM and GIFT with the following ranking of thrombogenicity: PP >
      PDLLA > PDLLA-HEMA > or = PDLLA-HEMA-heparin. GIFT significantly discriminated
      between the investigated materials. The surface modifications led to improved
      thromboresistance with reduced platelet adhesion and shape change. The main
      advantages of GIFT as compared with SEM are: no vacuum-drying or dehydration,
      less time-consuming procedure, fixation and fluorescence "staining" in one step,
      and suitability for computer-aided image analysis allowing quantitative
      assessment of platelet adhesion as well as imaging of the platelet shape change
      with high-contrast images. In conclusion, GIFT is a valid, rapid, and simple
      method for the quantitative determination of platelet/material interactions
      intended for the evaluation of thrombogenicity of biomaterials surfaces.

PMID- 10951379
TI  - Combined effect of titanium particles and TNF-alpha on the production of IL-6 by
      osteoblast-like cells.
AB  - To clarify the role of tumor necrosis factor (TNF)-alpha on osteoblast functions
      in the presence of metal particles, two human osteoblast-like cell lines (MG-63
      and SaOS-2) were cultured with TNF-alpha in the presence or absence of titanium
      particles in vitro. A combination of TNF-alpha and titanium particles showed
      additive effects on inhibition of cell proliferation and alkaline phosphatase
      production. On the other hand, production of interleukin-6, which is well known
      to induce osteoclastogenesis and to directly stimulate bone resorption, was
      additively stimulated by the combination of TNF-alpha and titanium particles.
      These results suggest that the association of TNF-alpha and titanium particles
      may play an important role in the pathogenesis of periprosthetic osteolysis
      through two different pathways: a reduced periprosthetic bone formation due to
      inhibition of osteoblast proliferation and alkaline phosphatase production, and
      osteoblast-mediated activation of osteoclastic bone resorption as suggested by
      the enhancement of interleukin-6 production.

PMID- 10951380
TI  - Influence of surface modifications to titanium on oral bacterial adhesion in
      vitro.
AB  - The influence of surface modifications to titanium on the initial adherence of
      Porphyromonas gingivalis ATCC33277 and Actinobacillus actinomycetemcomitans
      ATCC43718 was evaluated. Surface modifications were performed with dry processes
      including ion implantation (Ca(+), N(+), F(+)), oxidation (anode oxidation,
      titania spraying), ion plating (TiN, alumina), and ion beam mixing (Ag, Sn, Zn,
      Pt) with Ar(+) on polished pure titanium plates. Comparatively large amounts of
      P. gingivalis and A. actinomycetemcomitans adhered to polished titanium plates.
      The degree of P. gingivalis adhesion showed a positive correlation with surface
      energy and the amount of calcium-ion adsorption. Adherence of both P. gingivalis
      and A. actinomycetemcomitans increased on calcium-implanted surfaces compared
      with polished titanium surfaces, whereas adherence of P. gingivalis was
      remarkably decreased on alumina-coated surfaces. These findings indicate that
      titanium implants exposed to the oral cavity require surface modification to
      inhibit the adherence of oral bacteria, and that surface modification with a dry
      process is useful in controlling the adhesion of oral bacteria as well as
      ensuring resistance against wear.

PMID- 10951381
TI  - The cytotoxicity of corrosion products of nitinol stent wire on cultured smooth
      muscle cells.
AB  - Although nitinol is one of most popular materials of intravascular stents, there
      are still few confirmative biocompatibility data available, especially in
      vascular smooth muscle cells. In this report, the nitinol wires were corroded in
      Dulbecco's modified Eagle's medium with constant electrochemical breakdown
      voltage and the supernatant and precipitates of corrosion products were prepared
      as culture media. The dose and time effects of different concentrations of
      corrosion products on the growth and morphology of smooth muscle cells were
      evaluated with [(3)H]-thymidine uptake ratio and cell cycle sorter. Both the
      supernatant and precipitate of the corrosive products of nitinol wire were toxic
      to the primary cultured rat aortic smooth muscle cells. The growth inhibition was
      correlated well with the increased concentrations of the corrosion products.
      Although small stimulation was found with released nickel concentration of 0.95
      +/- 0.23 ppm, the growth inhibition became significant when the nickel
      concentration was above 9 ppm. The corrosion products also altered cell
      morphology, induced cell necrosis, and decreased cell numbers. The cell
      replication was inhibited at the G0-G1 to S transition phase. This was the first
      study to demonstrate the cytotoxicity of corrosion products of current nitinol
      stent wire on smooth muscle cells, which might affect the postimplantation
      neointimal hyperplasia and the patency rate of cardiovascular stents.

PMID- 10951382
TI  - The behavior of stainless steels in physiological solution containing complexing
      agent studied by X-ray photoelectron spectroscopy.
AB  - The passive film formed by electrochemical oxidation on two different stainless
      steels differing in molybdenum (Mo) content in physiological solution with and
      without the addition of complexing agent, i.e., citrate, was studied using X-ray
      photoelectron spectroscopy. The alloys were polarized at different oxidation
      potentials in the electrochemical chamber attached to the spectrometer. Thus, the
      composition of the film formed by oxidation was analyzed by X-ray photoelectron
      spectroscopy without prior exposure to air (quasi in situ). The passive film
      formed in physiological solution consists of two predominant oxides, i.e.,
      chromium and iron oxides. Oxides of alloying elements nickel and Mo are also
      detected in the film. It seems that the strong enrichment of oxidized chromium
      and Mo in the passive layer, and strong enrichment of Mo and depletion of iron at
      the metal surface underneath the passive layer, are responsible for the
      outstanding corrosion resistance of orthopedic stainless steel in physiological
      solution. Commercial AISI 304 is not suitable for orthopedic applications. The
      addition of complexing agent affects significantly the passivation behavior of
      orthopedic stainless steel, because it changes the distribution of the elements
      within the passive layer and at the metal surface underneath.

PMID- 10951383
TI  - Protein adsorption and platelet attachment and activation, on TiN, TiC, and DLC
      coatings on titanium for cardiovascular applications.
AB  - The hemocompatibility of a TiN/TiC/diamond-like carbon (DLC) multilayer
      structure, deposited on titanium substrates for use as coatings for a heart valve
      prosthesis, has been studied through the adsorption of blood proteins and the
      adhesion and attachment of blood platelets. All of the surfaces were
      characterized by stylus profilometry and water contact angles. The adsorption of
      albumin and fibrinogen to the surfaces was assessed using the Amido Black assay,
      whereas platelet attachment was studied by scanning electron microscopy and
      quantified using stereological techniques. The degree of platelet spreading on
      the surfaces was seen to correlate with differences in surface energy, indicated
      from contact angle measurements. The greatest spreading was seen on the more
      hydrophilic surfaces. When studying protein adsorption to the surfaces, no
      correlation could be determined between contact angle results and levels of
      adsorption, although the most hydrophilic surfaces did appear to promote greater
      amounts of fibrinogen adsorption. Thrombus formation was observed to some degree
      on all of the surfaces, with the exception of the DLC coating. This coating also
      promoted less spreading of platelets than the other surfaces. The good
      hemocompatibility of the DLC coating is attributed to its hydrophobicity and
      smooth surface, resulting in a higher ratio of albumin to fibrinogen than any of
      the other surfaces.

PMID- 10951384
TI  - Bioactivity of sol-gel bioactive glass coated alumina implants.
AB  - Alumina on alumina total hip arthroplasty has been in use for more than 25 years
      with encouraging results. However, an improvement of the alumina/bone interface
      still is required. The objective of this study was to investigate the in vitro
      and in vivo osteoconductive properties of sol-gel bioactive glass coated alumina
      implants. Two sol-gel glass compositions (58S Bioglass(R) and 77S Bioglass(R))
      were used as coatings on alumina substrates and implanted in a rabbit model. The
      58S sol-gel coating was employed in two configurations, single (A58S1) and double
      layer (A58S2). SEM analysis after one week in simulated body fluid revealed small
      crystals assumed to represent the initial phase of hydroxyapatite formation,
      whereas no clear conclusion could be drawn from Fourier transform infrared
      spectroscopy data. The percentage of bone in direct contact was greater for
      coated implants when compared to bulk alumina implants (p <0.001). In the case of
      A58S1 implants, bone percentage significantly increased from 45.1% after 3 weeks
      up to 87. 8% after 24 weeks of implantation (p = 0.0004). The presence of osteoid
      tissue, related to an aluminum release from the alumina substrates, was greatly
      diminished when compared to melt-derived glass-coated alumina implants.

PMID- 10951385
TI  - Synthetic nano-fibrillar extracellular matrices with predesigned macroporous
      architectures.
AB  - Scaffolding plays a pivotal role in tissue engineering. To mimic the architecture
      of a natural extracellular matrix component-collagen, nona-fibrous matrices have
      been created with synthetic biodegradable polymers in our laboratory using a
      phase-separation technique. To improve the cell seeding, distribution, mass
      transport, and new tissue organization, three-dimensional macroporous
      architectures are built in the nano-fibrous matrices. Water-soluble porogen
      materials are first fabricated into three-dimensional negative replicas of the
      desired macroporous architectures. Polymer solutions are then cast over the
      porogen assemblies in a mold, and are thermally phase-separated to form nano
      fibrous matrices. The porogen materials are leached out with water to finally
      form the synthetic nano-fibrous extracellular matrices with predesigned
      macroporous architectures. In this way, synthetic polymer matrices are created
      with architectural features at several levels, including the anatomical shape of
      the matrix, macroporous elements (100 microm to millimeters), interfiber distance
      (microns), and the diameter of the fibers (50-500 nm). These scaffolding
      materials circumvent the concerns of pathogen transmission and immuno-rejection
      associated with natural collagen. With the flexibility in the design of chemical
      structure, molecular weight, architecture, degradation rate, and mechanical
      properties, these novel synthetic matrices may serve as superior scaffolding for
      tissue engineering.

PMID- 10951386
TI  - Rapid activation of gill Na(+),K(+)-ATPase in the euryhaline teleost Fundulus
      heteroclitus.
AB  - The rapid activation of gill Na(+),K(+)-ATPase was analyzed in the mummichog
      (Fundulus heteroclitus) and Atlantic salmon (Salmo salar) transferred from low
      salinity (0.1 ppt) to high salinity (25-35 ppt). In parr and presmolt, Salmo
      salar gill Na(+),K(+)-ATPase activity started to increase 3 days after transfer.
      Exposure of Fundulus heteroclitus to 35 ppt seawater (SW) induced a rise in gill
      Na(+), K(+)-ATPase activity 3 hr after transfer. After 12 hr, the values dropped
      to initial levels but showed a second significant increase 3 days after transfer.
      The absence of detergent in the enzyme assay resulted in lower values of gill
      Na(+),K(+)-ATPase, and the rapid increase after transfer to SW was not observed.
      Na(+),K(+)-ATPase activity of gill filaments in vitro for 3 hr increased
      proportionally to the osmolality of the culture medium (600 mosm/kg > 500 mosm/kg
      > 300 mosm/kg). Osmolality of 800 mosm/kg resulted in lower gill Na(+),K(+)
      ATPase activity relative to 600 mosm/kg. Increasing medium osmolality to 600
      mosm/kg with mannitol also increased gill Na(+),K(+)-ATPase. Cycloheximide
      inhibited the increase in gill Na(+),K(+)-ATPase activity observed in
      hyperosmotic medium in a dose-dependent manner (10(-4) M > 10(-5) M > 10(-6) M).
      Actinomycin D or bumetanide in the culture (doses of 10(-4) M, 10(-5) M, and 10(
      6) M) did not affect gill Na(+),K(+)-ATPase. Injection of fish with actinomycin D
      prior to gill organ culture, however, prevented the increase in gill Na(+),K(+)
      ATPase activity in hyperosmotic media. The results show a very rapid and
      transitory increase in gill Na(+),K(+)-ATPase activity in the first hours after
      the transfer of Fundulus heteroclitus to SW that is dependent on translational
      and transcriptional processes. J. Exp. Zool. 287:263-274, 2000.

PMID- 10951387
TI  - Collagen study and regulation of the de novo synthesis by IGF-I in hemocytes from
      the gastropod mollusc, Haliotis tuberculata.
AB  - To evidence a collagen synthesis and identify which type(s) of collagen is
      present in hemocytes from the mollusc Haliotis tuberculata, we have performed
      three separate approaches, namely, de novo synthesis by cultured cells,
      immunological approaches, and northern blot analysis. We demonstrated first that
      after 40-hr labeling, the de novo synthesis of collagen in the cell layer of
      cultured hemocytes represents 9.48 +/- 1.25% with respect to the total
      [(3)H]proline-labeled protein synthesis. In addition, IGF-I elicited a
      significant stimulation of collagen synthesis in cultured hemocytes in a dose
      dependent manner from 10(-10) to 10(-8) M. The maximal stimulation (10(-9) M)
      induced an increase of 286 +/- 56% with respect to 100% control. By
      immunocytochemistry and immunoblotting, we showed that hemocytes present
      immunoreactive molecules to antibodies directed against the type I fibrillar
      collagen. In addition, using as a probe Hf 677 corresponding to a human pro
      alpha1(I) collagen cDNA and which encompasses the (Gly-X-Y) repeated sequence
      found in all Metazoa, four collagen transcripts of approximately 6.4, 5, 2.2, and
      2 kb in length have been detected. These data suggest the presence of fibrillar
      type I collagen in hemocytes and are compatible with the concept that these cells
      are involved in the extracellular matrix deposition, a cardinal function in
      tissue repair as well as in developmental processes. Our model may appear as an
      excellent system to study the role of growth factors on the regulation of
      collagen synthesis by molluscan hemocytes. J. Exp. Zool. 287:275-284, 2000.

PMID- 10951388
TI  - Introduction of a foreign gene into medakafish using the particle gun method.
AB  - We developed a procedure to introduce a foreign gene into fertilized eggs of
      medakafish (Oryzias latipes) using the particle gun method, which is one of the
      easiest and most reliable techniques for gene transfer. A plasmid construct with
      the green fluorescence protein (GFP) gene driven by the madakafish beta-actin
      gene promoter was successfully introduced into eggs, and the expression of GFP
      was observed in 20% of the primary transfectant (chimera) fish. In addition, germ
      line transmission of GFP was observed in 13% of the GFP-positive primary
      transfectant fish. The new application described here should enable us to
      investigate gene expression using the fish model on a routine basis without high
      technical sophistication. J. Exp. Zool. 287:285-293, 2000.

PMID- 10951389
TI  - Identification of maturation-inducing steroid in a freshwater perch Anabas
      testudineus and differential responses of intact follicles and denuded oocytes to
      cyclic AMP in oocyte maturation.
AB  - Postvitellogenic follicles of freshwater perch Anabas testudineus incubated with
      [(3)H]pregnenolone as exogenous precursor produced several metabolites, including
      17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (DHP) and 5 beta-pregnane-3 alpha, 17
      alpha,20 beta-triol (5 beta-3 alpha,17 alpha,20 beta-P). These were identified by
      chromatography, microchemical reactions, and crystallization to constant specific
      activity. Following stimulation with fish (perch) pituitary extract (FPE) there
      was significant high production of DHP and 5 beta-3 alpha,17 alpha,20 beta-P,
      concomitant with a high percentage of germinal vesicle breakdown (GVBD).
      Inhibitor of steroidogenesis (trilostane) and inhibitors of protein synthesis
      (cycloheximide and actinomycin-D) completely blocked FPE-induced pregnenolone
      metabolism and oocyte maturation. The effectiveness of various C(21) steroids in
      inducing GVBD was examined. Results indicate that DHP was the most potent inducer
      of GVBD than other structurally related C(21) steroids. In intact follicles, FPE
      stimulated production of DHP was shown to be mediated through the adenylate
      cyclase-cAMP pathway. Addition of IBMX or forskolin, which increases the
      endogenous cAMP level, as well as directly supplementing dbcAMP to the incubation
      medium, had no inhibitory effect on DHP-induced GVBD in the intact follicles. But
      all these agents were shown to inhibit GVBD in fully denuded oocytes. This study
      provides evidence that DHP, produced by postvitellogenic follicles through the
      adenylate cyclase-cAMP pathway, is the maturation-inducing steroid in freshwater
      perch and that the role played by cAMP in the induction of GVBD in intact
      follicles is different from that in the denuded oocytes. J. Exp. Zool. 287:294
      303, 2000.

PMID- 10951390
TI  - Activation of porcine oocytes using cyclopiazonic acid, an inhibitor of calcium
      dependent ATPases.
AB  - Cyclopiazonic acid (CPA), a potent inhibitor of endogenous calcium-dependent
      ATPases, is able to induce parthenogenetic activation in pig oocytes matured in
      vitro. Sixty-four percent of matured pig eggs cultured with 100 nM CPA for 4 hr
      were activated. A similar activation rate was observed in oocytes treated with
      thapsigargin, another inhibitor of calcium-dependent ATPases. The parthenogenetic
      development of CPA-activated eggs did not proceed beyond the 8-cell stage. The
      blockage of calcium channels by verapamil only slightly decreased the proportion
      of CPA-activated pig oocytes. This indicates that the release of calcium from
      intracellular stores is sufficient for oocyte activation and calcium influx from
      extracellular sources has no significant role. The significant decrease in CPA
      activated oocytes (100 nM of CPA for 4 hr) after a microinjection of heparin
      indicated that the mobilization of intracellular calcium stores is mediated
      through inositol trisphosphate receptors. On the other hand, the only slightly
      depressed activation rate in oocytes microinjected with ruthenium red and
      procaine indicates that CPA mobilizes a much smaller amount of calcium through
      the ryanodine receptors. The marked inhibitory effect of ophiobolin A and W7 on
      the activation of CPA-treated pig oocytes suggests that the calcium signal, as
      the second messenger, acts downstream through calmodulin. J. Exp. Zool. 287:304
      315, 2000.

PMID- 10951391
TI  - Ultrastructure and motility of the caudal epididymis spermatozoa from the volcano
      mouse (Neotomodon alstoni alstoni Merriam, 1898).
AB  - The volcano mouse Neotomodon alstoni alstoni is a genus endemic to the higher
      elevations of the Mexican transvolcanic belt. In the present study we examined
      for the first time the morphological features of the spermatozoa taken from the
      caudal epididymis of this species by transmission and scanning electron
      microscopy. Spermatozoan motility was studied in sucrose and bicarbonate
      solutions; vitality and morphology were observed by light microscopy.
      Transmission electron microscopy shows that the head of spermatozoon is
      asymmetric and possesses a large and curved hook. The axoneme of the spermatozoan
      tail is highly developed at fibers 1, 5, and 6. Absolute and relative
      measurements of the length of the head, the midpiece, and the rest of the tail
      were also obtained. N. alstoni alstoni spermatozoa were hyperactive in the
      presence of 290 mM sucrose and 10 and 20 nM bicarbonate solutions exhibited high
      motility (180-190 microm/sec), and high flagellum beating frequency (10-12 Hz).
      In contrast, the spermatozoa in 310 mM sucrose solution showed scarce motility
      (13.5 +/- 3.8 microm/sec) and low beating frequency (1.5 +/- 0.4 Hz). It is
      proposed that the volcano mouse spermatozoa possess some features very similar to
      other mammalian spermatozoa and that bicarbonate triggers caudal epididymal sperm
      motility of this species. J. Exp. Zool. 287:316-326, 2000.

PMID- 10951392
TI  - Barrett's mucosa: remodelling by the microenvironment.
AB  - Barrett's metaplasia and the associated adenocarcinoma are composed not only of
      epithelial cells, but also of inflammatory cells and endothelial cells in the
      lamina propria and around the tumour, respectively. The early incidence of
      vascular invasion and metastasis is a feature of Barrett's adenocarcinomas. A
      paper in this issue of The Journal of Pathology shows that vascular endothelial
      growth factor (VEGF) is expressed in both metaplastic cells and endothelial cells
      of pre-neoplastic Barrett's epithelium early in the development of neoplasia. It
      is becoming clearer that the harmful insults of acid and bile reflux alter not
      only the epithelium, but also the lamina propria. Cytokines such as tumour
      necrosis factor alpha (TNFalpha) or transforming growth factor (TGFalpha) are
      implicated in the formation of early Barrett's adenocarcinomas. From current
      knowledge it is possible to hypothesize that metaplastic cells, perhaps as a
      consequence of either TNFalpha or TGFalpha stimulation, secrete VEGF. VEGF can
      promote adjacent endothelial cell growth through phosphorylation of beta-catenin
      and vascular endothelial cadherin (VE-cadherin) in endothelial cells. In this de
      novo microenvironment, angiogenesis is therefore accelerated, enhancing the
      chance of microvascular invasion.

PMID- 10951393
TI  - Regulation of the differentiation and function of osteoclasts.
AB  - The osteoclast is the cell that resorbs bone. It has been known for many years
      that its formation and function are regulated by cells of the osteoblastic
      lineage. Recently the molecular basis for this regulation was identified;
      osteoblastic cells induce osteoclastic differentiation and resorptive activity
      through expression of tumour necrosis factor (TNF) activation-induced cytokine
      (TRANCE) (also known as RANKL, ODF, OPGL, and TNFSF11), a novel membrane-inserted
      member of the TNF superfamily. Osteoclastic regulation is assisted through
      secretion of an inhibitor, osteoprotegerin (OPG) (OCIF, TNFRSF11B), a soluble
      (decoy) receptor for TRANCE. Osteoclast formation and survival also depend on and
      are substantially enhanced by transforming growth factor-beta (TGF-beta), which
      is abundant in bone matrix. Surprisingly, not only TRANCE but also TNF-alpha can
      induce osteoclast formation in vitro from bone marrow-derived mononuclear
      phagocytes, especially in the presence of TGF-beta. Whether or not TNF-alpha does
      the same in vivo, its ability to generate osteoclasts in vitro has significant
      implications regarding the nature of osteoclasts and their relationship to other
      mononuclear phagocytes, and a possible wider role for TRANCE in macrophage
      pathobiology. A hypothesis is presented in which the osteoclast is a mononuclear
      phagocyte directed towards a debriding function by TGF-beta, activated for this
      function by TRANCE, and induced to become specifically osteoclastic by the
      characteristics of the substrate or signals from bone cells that betoken such
      characteristics.

PMID- 10951394
TI  - Angiogenesis in the neoplastic sequence of Barrett's oesophagus. Correlation with
      VEGF expression.
AB  - The purpose of this study was to determine the angiogenic profile of human
      oesophageal adenocarcinoma. This study was carried out on a large series of
      surgically resected Barrett's adenocarcinomas and associated preneoplastic
      lesions. Vascularization was quantified by microvessel counting and measurement
      of the percentage microvessel surface area after immunohistochemistry using the
      CD34 antibody. The expression of vascular endothelial cell growth factor (VEGF)
      was also examined by immunohistochemistry. Results were correlated with clinico
      pathological data and prognosis. Vascularization, assessed by both microvessel
      counting and measurement of the microvessel surface, was statistically higher in
      superficial cancers than in others. Higher vascularization was correlated with a
      lower rate of lymph node and distant metastasis, as well as with better survival.
      However, when superficial carcinomas were excluded from the study, microvessel
      count failed to provide any significant prognostic information. Irrespective of
      the inclusion or exclusion of superficial tumours, the expression of VEGF was
      correlated with a higher vascularisation but did not provide prognostic
      significance. It is concluded that high angiogenic properties are acquired in
      precancerous lesions and early cancers in Barrett's oesophagus. Vascularization
      as assessed by both microvessel counting and measurement of the microvessel
      surface is not informative for prognosis in infiltrative Barrett's
      adenocarcinomas. The expression of VEGF is correlated with vascularization, but
      has no independent prognostic relevance.

PMID- 10951395
TI  - Nuclear profiles of cancer cells reveal the metastatic potential of gastric
      cancer.
AB  - Nuclear profiles have been reported as useful prognostic predictors in various
      cancers. Data from computerized morphometry are objective and can be quickly
      derived using conventional microscopic analysis, but image analysis of nuclear
      features has only rarely been applied to investigations of gastric cancer. The
      aim of this study was to evaluate the correlation between one of these
      morphological nuclear features and the clinicopathological parameters in patients
      with gastric cancer. The morphometric nuclear feature (nuclear area) was analysed
      in 400 patients with gastric cancer. In each case, 300 cancer nuclei on routine
      haematoxylin and eosin-stained slides were analysed through the use of a computer
      assisted image analysis system which traced the nuclear profiles
      (magnificationx400) on a computer monitor. The morphometric data were compared
      with the patients' clinicopathological status and survival rate. The mean nuclear
      area (NA) of cancer cells from 400 cases of gastric cancer was 47.2 microm(2).
      The NAs of cancer cells from tumours with microvessel invasion (lymphatic or
      venous invasion), lymph node metastasis or hepatic metastasis at the time of
      operation were significantly larger than those of cancer cells from tumours
      without such invasion or metastases. Cytokeratin (CK) immunostaining was
      performed on 2577 lymph nodes from 91 patients with advanced gastric cancer (pT3,
      pN0, pM0, stage II) to detect micrometastases. CK-positive lymph nodes were
      detected in 350 of 2577 lymph nodes (13. 6%) and in 62 of 91 patients (68.1%).
      The mean NA of cancer cells from 62 tumours with micrometastases (44 microm(2))
      was larger than that of cancer cells from 29 tumours without micrometastases
      (38.8 microm(2), p=0.043), and a significant positive correlation was detected
      between the NAs of cancer cells from 91 tumours and the number of micrometastatic
      lymph nodes of 91 patients (rho=0.278, p=0. 008). Cancer cells with large NA
      correlated strongly with haematogenous and lymph node recurrence or relapse after
      gastrectomy and the NA of cancer cells was identified as an independent
      prognostic factor in gastric cancer. Nuclear morphometry is an objective,
      reproducible, and technically uncomplicated procedure. The NA of cancer cells
      correlates closely with the metastatic potential of gastric cancer. Nuclear
      morphometry may therefore be useful for the selection of patients who are at risk
      of haematogenous or lymph node metastatic recurrence after surgery.

PMID- 10951396
TI  - Reduced expression of p27/Kip1 is associated with the development of pulmonary
      adenocarcinoma.
AB  - p27/Kip1 (p27), a negative regulator of cell proliferation, is a powerful
      prognostic marker in non-small cell lung carcinoma. To clarify the significance
      of p27 aberrations in the tumourigenesis of lung adenocarcinoma, p27 expression
      was investigated by immunohistochemistry in lung adenocarcinoma and its precursor
      lesion, atypical adenomatous hyperplasia (AAH), and correlated with the
      expression of Ki-67, cyclin D1, and cyclin E. The p27 labelling index decreased
      in parallel with tumour progression (24.0% to 4.5%) and was found to be lower in
      neoplastic lesions than in normal bronchiolar epithelial cells (48.8%). There was
      a negative correlation between p27 and Ki-67 expression (rho=-0.384, p<0.001).
      Cyclin E-positive lesions (with labelling index >/=5%) were found only in overt
      adenocarcinomas. The Ki-67 labelling index of cyclin E-positive, high (>/=10%)
      p27 expressers was lower than that of cyclin E-positive, low (<10%) p27
      expressers (16.8% vs. 42.6%; p=0. 046) and was similar to that of cyclin E
      negative adenocarcinomas (15.0%). These results indicate that reduced p27
      expression is associated with and may play a role in progression during the
      development of pulmonary adenocarcinoma.

PMID- 10951397
TI  - Assessment of ret/PTC-1 rearrangements in neoplastic thyroid tissue using TaqMan
      RT-PCR.
AB  - Among oncogenes studied in thyroid cancers, a specific activated form of c-ret
      has been found in a minority of papillary thyroid carcinomas (PTCs). In these
      tumours, c-ret is activated when by somatic rearrangements, the intracellular
      domain of RET is juxtaposed with the amino-terminal portion of a different donor
      gene such as H4, thereby generating a chimeric transcript (ret/PTC-1). The
      functional effects of c-ret activation and its prognostic implications are
      currently unclear. This study was undertaken to assess the frequency of RET/PTC-1
      expression, any distinctive features of positive tumours to which it might be
      related, and its prognostic importance. Archival material from 88 thyroid
      neoplasms [50 PTCs, eight anaplastic carcinomas (ATCs), 25 follicular thyroid
      carcinomas (FTCs) and five follicular adenomas (FAs)] were analysed for ret/PTC-1
      and H4 expression using 5' nuclease assay (TaqMan RT-PCR). RNA from the TPC-1
      cell line was included as a positive control for c-ret activation. No FTC or FA
      displayed activation of ret/PTC-1, though all expressed H4. c-ret activation was
      found in 24% of PTCs (12 of 50), in 87.5% of ATCs (7 of 8), and in 33% of the
      combined PTC/ATC group. The frequency of c-ret activation in the aggressive ATC
      variants noted here suggests that ret/PTC-1-positive PTCs might also have a
      similar poor prognosis and a follow-up study on this cohort is in progress.
      Ninety per cent of ret/PTC-1-positive tumours failed to express H4, a phenomenon
      that has not been described previously and which may have considerable bearing on
      tumour morphology. A statistically significant proportion (58%) of ret/PTC-1
      positive, H4-negative PTCs was associated with chronic inflammatory cell
      infiltration of the tumour and/or the surrounding thyroid. This association has
      not been reported previously.

PMID- 10951398
TI  - Hot microscopic areas of iodine-deficient euthyroid goitres contain
      constitutively activating TSH receptor mutations.
AB  - Constitutively activating TSH receptor mutations have been established as the
      most common molecular basis for the pathogenesis of toxic thyroid nodules. These
      mutations result in uncontrolled signalling through the TSH receptor that is
      likely to cause hyperfunction and proliferation. The incidence of toxic
      multinodular goitres has been demonstrated to be related to iodine deficiency.
      Moreover, scintigraphically autonomous areas are found in 40% of euthyroid
      goitres from iodine-deficient areas. To investigate the molecular cause of these
      autonomous areas, small autoradiographically hot areas were examined for somatic
      TSH receptor mutations using archival tissue sections from 14 patients with
      euthyroid goitres, which had been originally prepared nearly 20 years ago. All
      patients had received (125)I 17 h preoperatively for the autoradiographic
      investigation of their thyroid. Areas with high and low (125)I-labelling on
      autoradiography sections were collected separately either from serial paraffin
      embedded tissue sections, or Eukitt-embedded tissue sections containing the
      autoradiograph. After genomic DNA extraction, the transmembrane segment of the
      TSH receptor was PCR-amplified and directly sequenced. Somatic TSH receptor
      mutations were identified in areas with high (125)I-labelling in four patients:
      A623I, L629P, F631L, and T632I. This is the first evidence that TSH receptor
      mutations occur in microscopic areas with increased (125)I-labelling in euthyroid
      goiters and it suggests that TSH receptor mutations in these areas confer the
      potential to develop into toxic thyroid nodules. It is therefore very likely that
      toxic thyroid nodules originate from small autonomous areas in iodine-deficient
      euthyroid goitres that contain a TSH receptor mutation.

PMID- 10951399
TI  - Differentiation of multicentric origin from intra-organ metastatic spread of
      hepatocellular carcinomas by comparative genomic hybridization.
AB  - In hepatocellular carcinoma (HCC), multifocal growth may be due to intrahepatic
      metastatic spread or to the multicentric origin of clonal neoplasms. Although
      this issue is of potential clinical and prognostic importance, reliable
      differentiation cannot be achieved using clinical or morphological criteria
      alone. In this study, comparative genomic hybridization (CGH) was used to
      differentiate between metastatic spread and multicentric growth in two cases of
      HCC. In the first case, six carcinoma nodules were examined. The affected
      chromosomes and their pattern of aberrations were almost identical for all six
      nodules. In addition to aberrations of chromosomes 1, 4, 9, and 13, further
      aberrations were observed for chromosomes 2, 5, 7, and 17, which are less typical
      for HCC. These findings were seen as indicative of metastatic spread of the HCC.
      In the second case, 75% (3/4) of the nodules showed comparable aberration
      patterns involving chromosomes 1, 4, 8, 13, and 17, together with a number of
      further aberrations also not frequently seen in HCC including chromosomes 5, 7,
      10, 12, 14, and 18. Chromosomes 4, 5, 8, 10, and 12 were also altered in the
      fourth nodule examined for this case, but they exhibited a unique aberration
      pattern. Additionally, gain of chromosome 15q was seen in only this fourth
      nodule. In the two cases examined, metastatic spread and multicentric origin of
      HCC could be differentiated by different patterns of karyotypic change. The CGH
      results were confirmed by fluorescence in situ hybridization (FISH). In
      conclusion, CGH facilitates the differentiation of multicentric growth from
      metastatic spread in HCC and appears to be superior to techniques previously used
      to resolve this clinically important diagnostic problem.

PMID- 10951400
TI  - Expression of p53 in oral squamous cell carcinoma is associated with the presence
      of IgG and IgA p53 autoantibodies in sera and saliva of the patients.
AB  - Around 50% of head and neck cancers are known to have aberrations of the p53
      gene. Overexpression of the mutant p53 protein can induce a specific humoral
      response in cancer patients. Matched saliva, serum, and tissue samples from 26
      patients with histologically confirmed oral squamous and verrucous carcinoma were
      investigated. p53 protein expression was evaluated by immunohistochemistry and
      antibodies specific for 53 protein were analysed in sera and whole mouth saliva
      by ELISA, immunoprecipitation, and competition assays; 16/25 (64%) samples
      demonstrated the stabilized p53 protein in tissues and 7/26 (27%) had a high
      level of p53 antibody in serum. In samples where matching saliva was available,
      p53 antibody was also present in saliva. In some tumours, only IgA-type p53
      antibody was detected. p53 antibodies were found only in the serum and saliva of
      patients who showed p53 overexpression in their tumour tissues. These results
      demonstrate that detection of p53 antibodies can offer a specific and non
      invasive method for the detection of a subset of tumours with p53 aberrations.

PMID- 10951401
TI  - Expression patterns of E-cadherin, involucrin, and connexin gap junction proteins
      in the lining epithelia of inflamed gingiva.
AB  - The structural integrity and functional differentiation of the lining epithelium
      were studied in relation to inflammatory changes associated with destructive
      periodontitis. In the different regions of lining epithelia from clinically
      healthy gingiva and periodontitis, comparisons were made of the expression
      patterns of E-cadherin, which is critical in intercellular adhesion; of proteins
      associated with gap junction communication channels; and of involucrin, which is
      a key marker of differentiation in stratified epithelia. Filamentous actin (F
      actin), which is important in cell structural integrity, attachment, and
      migration, was also examined. Semiquantitative immunohistochemical analysis
      revealed that in both clinically healthy gingiva and lesions of advanced
      periodontitis, expression patterns of E-cadherin, involucrin, and connexins 26
      and 43 were similar, with a statistically significant reduction in staining
      intensity from the external oral epithelium, through the gingival sulcus, to the
      junctional epithelium or pocket epithelium, respectively. Furthermore, there was
      a striking reduction in staining for E-cadherin, involucrin, and both connexins
      in the pathological lining epithelium of the periodontal pocket. These changes
      were associated with marked alterations of filamentous actin expression,
      collectively indicating profound perturbation of the epithelial structure. The
      data reported support the concept that the ability of the pathological lining
      epithelium to function as an effective barrier against the ingress of microbial
      products into the tissues is severely compromised.

PMID- 10951402
TI  - Human peritoneal adhesions are highly cellular, innervated, and vascularized.
AB  - Peritoneal adhesions are a major complication of healing following surgery or
      infection and can lead to conditions such as intestinal obstruction, infertility,
      and chronic pain. Mature adhesions are the result of aberrant peritoneal healing
      and historically have been thought to consist of non-functional scar tissue. The
      aim of the present study was to analyse the cellular composition, vascularity,
      and extracellular matrix distribution of human peritoneal adhesions, to determine
      whether adhesions represent redundant scar tissue or are dynamic regenerating
      structures. Furthermore, the histological appearance of each adhesion was
      correlated with the clinical history of the patient, to determine whether
      maturity or intraperitoneal pathology influences adhesion structure. Human
      peritoneal adhesions were collected from 29 patients undergoing laparotomy for
      various conditions and were prepared for histology, immunocytochemistry, and
      transmission electron microscopy. All adhesions were highly vascularized,
      containing well-developed arterioles, venules, and capillaries. Nerve fibres,
      with both myelinated and non-myelinated axons, were present in adhesions from
      nearly two-thirds of the patients, with increased incidence in those with a
      malignancy. Approximately one-third of the adhesions contained conspicuous smooth
      muscle cell clusters lined by collagen fibres of heterogeneous size. Adipose
      tissue was a consistent feature of all the adhesions, with some areas displaying
      fibrosis. There appeared to be no correlation between the estimated maturity or
      site of each adhesion and its histological appearance. However, intraperitoneal
      pathology at the time of surgery did influence the incidence of some histological
      features, such as the presence of nerve fibres, clusters of smooth muscle cells,
      and inflammation. This study challenges previous concepts that adhesions
      represent non-functional scar tissue and clearly demonstrates that established
      adhesions are highly cellular, vascularized, and innervated, features more
      consistent with dynamic, regenerating structures.

PMID- 10951403
TI  - In situ expression of fibrogenic growth factors and their receptors in biliary
      atresia: comparison between early and late stages.
AB  - Progressive fibrosis, despite successful surgical treatment, is one of the
      serious complications of biliary atresia. To understand the mechanism of this
      fibrosis, the in situ expression of fibrogenic growth factors (TGF-beta and PDGF)
      and their corresponding receptors was studied by immunohistochemistry using
      frozen sections. The results were compared between the early (n=12) and late
      (n=6) stages. The early stage was characterized by abundant expression of all
      ligands and receptors, together with type I procollagen (PC-I). The major
      cellular sources were activated fibroblasts/myofibroblasts distributed mostly in
      the portal tracts. Macrophages also expressed all the ligands and the receptors,
      but to a lesser degree. Bile duct cells strongly expressed TGF-beta RI and RII
      and PDGF AA and BB, but focally expressed TGF-beta. All of these decreased in the
      late stage of biliary atresia. These results suggest that TGF-beta and PDGF play
      important roles in the fibrogenesis of biliary atresia, especially in its early
      stage, acting either by autocrine or paracrine mechanisms involving activated
      fibroblasts/myofibroblasts, bile duct cells, and macrophages.

PMID- 10951404
TI  - Collagen type I synthesized by pancreatic periacinar stellate cells (PSC) co
      localizes with lipid peroxidation-derived aldehydes in chronic alcoholic
      pancreatitis.
AB  - Chronic alcoholic pancreatitis (CAP) is characterized by progressive pancreatic
      fibrosis and loss of the acinar cell mass, but the pathogenesis of pancreatic
      fibrosis in the human is poorly understood. It has been recently suggested that
      lipid peroxidation-derived aldehydes such as 4-hydroxynonenal (HNE) are involved
      in tissue damage and fibrosis in other organs. The aim of this study was to
      evaluate the role of oxidative stress in the development of alcohol-induced
      pancreatic fibrosis in humans, and to assess the contribution of pancreatic
      periacinar stellate cells (PSC) in the in vivo synthesis of extracellular matrix
      components during CAP. Lipid peroxidation was evaluated in tissue specimens
      obtained from patients with CAP who underwent surgical procedures, by
      immunohistochemistry using a monoclonal antibody directed against HNE-protein
      adducts. Immunohistochemical determination of collagen type I, alpha-smooth
      muscle actin (alpha-SMA), and the beta subunit of human platelet-derived growth
      factor (PDGF-Rbeta) was also performed. In addition, the tissue mRNA expression
      of procollagen I, PDGF-Rbeta, and transforming growth factor-beta1 (TGF-beta1)
      was evaluated by in situ hybridization. In CAP, increased formation of HNE
      protein adducts was evident in acinar cells adjacent to the interlobular
      connective tissue that stained positively for collagen type I. HNE staining was
      absent in normal pancreas. Several non-parenchymal periacinar cells (PSC)
      underlay the HNE-stained acinar cells. Those PSC stained positively for alpha-SMA
      and PDGF-Rbeta and showed active synthesis of procollagen type I by in situ
      expression of the specific mRNAs. The pattern of expression of PDGF-Rbeta mRNA
      reflected that observed in immunostaining, showing increased amounts of
      transcripts in PSC. TGF-beta1 mRNA expression was increased in CAP, but
      transcripts were found in several cell types including PSC, acinar, and ductal
      cells. These results indicate that significant lipid peroxidation phenomena occur
      in CAP and that they are associated with active synthesis of collagen by PSC.

PMID- 10951405
TI  - Preliminary report of impaired oestrogen receptor-alpha expression in bone, but
      no involvement of androgen receptor, in male idiopathic osteoporosis.
AB  - In western countries, osteoporosis affects at least 1 in 12 of all adult males
      and a third of osteoporotic men have idiopathic disease (MIO). Both oestrogen and
      testosterone are now known to be important to the male skeleton. As normal
      oestrogen levels have been found in younger MIO cases, it is hypothesized that,
      in bone, their responses to gonadal steroids may be defective, through impaired
      receptor expression. This study therefore compared oestrogen receptor (ER)-alpha
      and androgen receptor (AR) expression, by indirect immunofluorescence and semi
      quantitative image analysis, in undecalcified fresh frozen bone sections from MIO
      patients (33-56 years), age-matched control men (n=7), and, for reference,
      ovarian steroid-replete (n=7) and -deficient women (n=6). In normal men, 23%+/
      SEM 6% osteoblasts and 14%+/-SEM 2% osteocytes expressed ERalpha protein, similar
      to hormone-replete women. Although receptor expression decreased in hormone
      deficient women, loss of ERalpha protein in MIO patients was more severe (1%+/
      SEM 0.5% osteocytes, 2%+/-SEM 1% osteoblasts expressed receptor). In all four
      groups, there was little osteocyte AR expression, but in the women, a proportion
      of osteoblasts were receptor-positive. Deficient osteoblast and osteocyte ERalpha
      protein expression could explain the bone loss in these MIO patients.

PMID- 10951406
TI  - Rheumatoid arthritis synovial macrophage-osteoclast differentiation is
      osteoprotegerin ligand-dependent.
AB  - Osteoprotegerin ligand (OPGL) is a newly discovered molecule which is essential
      for osteoclast differentiation. Both OPGL and its soluble decoy receptor,
      osteoprotegerin (OPG), which inhibits osteoclast formation, are known to be
      produced by osteoblasts and inflammatory cells found in the rheumatoid arthritis
      (RA) synovium. In this study, RA synovial macrophages were incubated in the
      presence or absence of OPGL, macrophage-colony stimulating factor (M-CSF), and
      dexamethasone for various time points. The results indicated that osteoclast
      formation from RA synovial macrophages is OPGL-dependent and that OPGL and M-CSF
      are the only humoral factors required for RA synovial macrophage-osteoclast
      differentiation. OPG was found to inhibit osteoclast formation by RA synovial
      macrophages in a dose-dependent manner. This study has shown that macrophages
      isolated from the synovium of RA patients are capable of differentiating into
      osteoclastic bone-resorbing cells; this process is OPGL- and M-CSF-dependent and
      is modulated by corticosteroids. Cellular (T and B cells, dendritic cells) and
      humoral factors in RA synovium and bone may influence osteoclast formation and
      bone resorption by controlling OPGL/OPG production.

PMID- 10951407
TI  - Increased TIMP/MMP ratio in varicose veins: a possible explanation for
      extracellular matrix accumulation.
AB  - Primary varicose veins are functionally characterized by venous back-flow and
      blood stagnation in the upright position. Dilatation and tortuosity provide
      evidence for progressive venous wall remodelling, with disturbance of smooth
      muscle cell/extracellular matrix organization. Affected areas are not uniformly
      distributed, some areas being hypertrophic, whereas others are atrophic or
      unaffected. In 12 varicose veins and ten control veins, the proteolytic
      enzyme/inhibitor balance which may participate in the remodelling of the venous
      wall was investigated. For this purpose, the presence and enzymatic activity of
      matrix metalloproteinases (MMP-2, MMP-9), tissue inhibitors of MMPs (TIMP-1, TIMP
      2), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators (PAs), and
      plasminogen activator inhibitor-1 (PAI-1) were quantified by western blot and
      gelatin or plasminogen-casein zymography. In addition, MMP-2, TIMP-1, TIMP-2, and
      PAI-1 levels were measured by ELISA. A high TIMP-1 level and a low MMP-2
      level/activity were found in varicose veins (p<0.005), resulting in a three-fold
      increase in the TIMP-1/MMP-2 ratio in varicose versus control veins. Levels of
      PAs (uPA and tPA) as well as PAI-1 were both lower in varicose veins (p<0.005),
      with minimal change in the PAI/PA ratio. These results demonstrate that varicose
      veins are characterized by a higher than normal TIMP/MMP ratio, which may
      facilitate extracellular matrix accumulation in the diseased venous wall.

PMID- 10951410
TI  - Guidelines for cancer care: is the time at hand?

PMID- 10951408
TI  - Localized Wegener's granulomatosis: predominance of CD26 and IFN-gamma
      expression.
AB  - The immune response in Wegener's granulomatosis (WG) has been characterized as a
      predominant, potentially pathogenic Th1-like reaction by blood T cells and T-cell
      clones from diseased tissues. To elucidate further the immunopathogenic
      mechanisms, this study analysed the phenotypes of inflammatory infiltrates in
      frozen nasal biopsies with involvement of the upper respiratory tract only
      (localized or 'initial phase' WG) and with multi-organ involvement, including
      systemic vasculitis (generalized WG). The expression and production of Th1 and
      Th2 cytokines were examined in tissue specimens and peripheral blood mononuclear
      cells (PBMCs) of localized and generalized WG. The number of CD3+ T cells in
      inflammatory infiltrates ranged from 50 to 70%, together with approximately 30%
      CD14+ monocytes/macrophages. An average of 40% of T cells expressed CD26 in nasal
      biopsies of localized WG, compared with about 16% in specimens of generalized WG.
      In parallel, a higher number of interferon-gamma (IFN-gamma)-positive cells were
      detected in nasal tissue of localized than in generalized WG. PBMCs from
      localized WG similarly exhibited higher spontaneous IFN-gamma production in
      contrast to generalized WG (207 vs. 3 pg/ml, p<0.05). Interleukin-4 (IL-4) mRNA
      was found in higher amounts in generalized than in localized WG. IL-4 production
      was negligible in both disease and controls. In addition, both IL-10 mRNA and IL
      10 protein levels of activated PBMCs from localized WG were elevated when
      compared with generalized disease (574 vs. 154 pg/ml, p<0.05) or healthy controls
      (574 vs. 246 pg/ml, p<0.05). It is conluded that in nasal tissues, mainly
      CD4+/CD26+ T cells as well as IFN-gamma-positive cells may support a polarized
      Th1-like immune response. Furthermore, the data suggest that this in situ immune
      response is already initiated and established in localized WG, accompanied by
      increased peripheral IFN-gamma and IL-10 production.

PMID- 10951409
TI  - Functional implications of tissue factor localization to cell-cell contacts in
      myocardium.
AB  - Recently published studies suggest that the procoagulant receptor protein tissue
      factor (TF) is involved in vitro in cell adhesion and migration, via an
      interaction of its cytoplasmic domain with cytoskeletal proteins. Interestingly,
      TF is abundantly expressed in myocardium, but not in skeletal muscle. To
      elucidate the possible roles of TF in the myocardium, this study examined the
      cellular distribution of TF in relation to cytoskeletal proteins, as well as its
      relative amounts in different segments of premature, mature, and pathologically
      altered cardiac muscle. In juvenile and adult hearts, TF was predominantly
      detectable in the transverse part of the intercalated discs, where it co
      localized with cytoskeletal proteins such as desmin and vinculin. The lowest
      amount of TF was observed in right atrial and the highest in left ventricular
      myocardium, which correlated with the number of contact sites of cardiomyocytes
      in these segments of the cardiac muscle. Lower levels of TF were present in
      structurally altered myocardium from patients with hypertension or ventricular
      hypertrophy. In addition, TF expression was decreased in human heart during
      sepsis and transiently decreased in rabbit heart in an endotoxaemia model, which
      indicates that a reduction in TF may contribute to cardiac failure in sepsis. The
      microtopography of TF at cardiomyocyte contact sites indicates that TF may play a
      structural role in the maintenance of cardiac muscle.

PMID- 10951411
TI  - Is total mesorectal excision really important?

PMID- 10951412
TI  - Prospective phase II trial of alternating intravesical Bacillus Calmette-Guerin
      (BCG) and interferon alpha IIB in the treatment and prevention of superficial
      transitional cell carcinoma of the urinary bladder: preliminary results.
AB  - BACKGROUND AND OBJECTIVE: Evaluate the efficacy and toxicity of alternating
      intravesical instillation of Bacillus Calmette-Guerin(BCG) and Interferon alpha2
      b (IFN) in the treatment and prevention of recurrence of superficial transitional
      cell carcinoma (TCC) of the urinary bladder. METHODS: Patients with Ta, T1 tumors
      and carcinoma in situ, either recurrent (TaG1, T1G1) or primary/recurrent TaG2
      TaG3, T1G2, T1G3 and Tis (T: Tumor stage, G: grade) are eligible. All patients
      received intravesical BCG 81 mg on Weeks 1, 3, 5 and 7 and IFN 100 million units
      on Weeks 2, 4, 6 and 8. Cystoscopy performed 4 weeks after completion of therapy,
      and every 3 months thereafter. RESULTS: There was a total of 37 patients.
      Thirteen had TaG2, 13 T1G2, 1 T1G1, 4 TaG1, 1 TaG3, 3 T1G3 and 7 Tis (5
      concurrent with other above tumors). Index lesion cleared in 7/10 patients. With
      a median follow-up of 26.2 month, 22 patients (59%) failed above therapy. Median
      time to treatment failure was 7 months. Seven, 6 and 9 patients recurred at a
      higher, lower and same stage or grade respectively. No grade 3 or 4 toxicity was
      encountered. CONCLUSIONS: Alternating intravesical BCG and IFN is effective and
      well tolerated therapy for superficial TCC of urinary bladder.

PMID- 10951413
TI  - Significance of serum and tissue carcinoembryonic antigen for the prognosis of
      gastric carcinoma patients.
AB  - BACKGROUND AND OBJECTIVES: Carcinoembryonic antigen (CEA) has been widely
      accepted as a tumor marker useful in the diagnosis and management of colorectal
      carcinoma. When CEA levels are positive in patients with gastric carcinoma, they
      could be useful prognostic indicators. The value of CEA as a tumor marker for
      gastric carcinoma, however, remains a matter of controversy. The purpose of this
      study was to determine whether preoperative serum CEA value and tissue CEA
      staining are useful prognostic indicators for gastric carcinoma. METHODS: We
      measured preoperative serum CEA levels by radioimmunoassay and stained tissue CEA
      production by tumor cells from gastric carcinomas using immunohistochemical
      staining in patients with gastric carcinoma. RESULTS: The patients with
      preoperative serum CEA levels >10.0 ng/mL had a more prominent serosal invasion,
      much more lymph node involvement, more advanced stage and more poorly
      differentiated than did the patients with preoperative serum CEA levels <5.0
      ng/mL. The survival rate of patients with serum CEA levels >10.0 ng/mL was poorer
      than those of patients with serum CEA levels between 5.0 and 10.0 ng/mL, and
      those of patients with serum CEA levels <5.0 ng/mL (P < 0.05). The preoperative
      serum CEA levels and tumor CEA-positivity were correlated (P < 0.05). In patients
      with lymph node metastases, the CEA-positivity (78.0%) was higher than in
      patients without lymph node metastasis (63.2%) (P < 0.05). A correlation was also
      found between the depth of tumor invasion and tissue CEA-positivity (P < 0.001).
      The postoperative survival rate was significantly better in the CEA-negative
      staining group (78.0%) than in the CEA-positive staining group (60.0%).
      CONCLUSIONS: These data suggest that preoperative serum CEA levels and staining
      for CEA in gastric carcinoma tissue sections may have a predictive value in
      determining prognostic information for patients with resectable gastric
      carcinoma.

PMID- 10951414
TI  - Regional hyperthermia in the treatment of primary hepatic carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this research was to investigate the
      clinical significance of regional hyperthermia in the treatment of primary
      hepatic carcinoma (PHC). METHODS: The regional hyperthermia (60 degrees C) was
      used whenever there was suspicion of residual cancer tissues on the edge of the
      hepatic resection. The hyperthermia was maintained for about 5-20 min depending
      on the size and the amounts of residual nodulus. If there was obvious necrosis on
      the hyperthermia-treated site, the solidified tissues were removed. Otherwise,
      the solidified tissues were kept in situ. RESULTS: There were 68 cases of PHC
      patients in this study. The patients were divided into 4 groups: A, lobectomy, 14
      cases; B, lobectomy plus regional hyperthermia, 12 cases; C, regional
      hepatectomy, 16 cases; D, regional hepatectomy plus regional hyperthermia, 26
      cases. All patients were followed after their operations. The mean survival time
      of the 4 groups was as follows: Group A, 346.5 days (186-921 days); Group B,
      432.6 days (254-1189 days); Group C, 525.4 days (192-1016 days); and Group D,
      1142 (from 318 days to seven years and two months) days. There were significant
      differences between Groups A and B (P < 0.01) and between Groups C and D (P <
      0.01). It seems that regional hyperthermia on the hepatic resection edge can
      prolong patients' survival time. CONCLUSIONS: Regional hyperthermia on the
      hepatic resection edge is helpful for prolonging patients' survival time in the
      treatment of primary hepatic carcinoma.

PMID- 10951415
TI  - Commentary.

PMID- 10951416
TI  - Autopsy findings in patients with esophageal carcinoma: comparison between
      resection and nonresection groups.
AB  - The prognosis of patients with esophageal cancer is poor, despite attempts at
      aggressive multimodality treatment. To yield some important information that
      could help to improve operative methods and multimodality treatments, we compared
      autopsy findings such as the extent of local and metastatic spread of cancer in
      resection (n = 33) and nonresection (n = 38) groups of patients who had had
      esophageal cancer. Residual or recurrent esophageal cancer was identifiable in
      71.9% of patients in the resection group and 94.4% of patients in the
      nonresection group. Local residual cancer was identified much less frequently in
      the former group than in the latter (21.2% vs. 94.4%) (P < 0.0001). The most
      frequent mode of metastasis was hematogenous, occurring in 51.5% of the resection
      cases and 63.9% of the nonresection cases. Lymph-node metastasis was also
      observed frequently, being present in 51.5% of resection cases and 58.3% of
      nonresection cases. Serosal dissemination of cancer was found in 36.4% of
      resection cases and 25.0% of nonresection cases. The low incidence of localized
      disease suggests that esophagectomy, even though palliative in some cases, is
      effective as a treatment for esophageal cancer. The high incidence of lymph-node
      and hematogenous metastasis after esophagectomy implies that more extensive lymph
      node dissection and stronger adjuvant chemotherapy might be required.

PMID- 10951417
TI  - Initial experience with breast biopsy utilizing the Advanced Breast Biopsy
      Instrumentation (ABBI).
AB  - The Advanced Breast Biopsy Instrumentation (ABBI) system combines a cylindrical
      single-use biopsy device with digital stereotactic imaging that achieves
      targeting of radiographic lesions to +/- 1 mm. This minimally invasive technique
      uses digital stereotactic imaging to perform excisional biopsies of suspicious,
      nonpalpable mammographic lesion. This allows complete removal of specimens in a
      one-step procedure that does not involve separate trips to radiology and then
      surgery. The authors' initial 170 cases utilizing the ABBI system were reviewed.
      The accuracy of specimen targeting, the success rate of lesion removal, and
      operative complications were some of the issues assessed. Five cases were not
      suitable for the procedure: the mammographic lesion was not visualized in one,
      and the breast was too thin on compression in four. There was successful removal
      of the lesion in 165 of the remaining cases. There were no local wound
      complications, and patient satisfaction was high in all completed biopsies. The
      ABBI system is an effective new form of minimally invasive breast surgery. It
      provides complete excision of mammographic abnormalities.

PMID- 10951418
TI  - Modified radical mastectomy using harmonic scalpel.
AB  - BACKGROUND AND OBJECTIVES: Modified radical mastectomy (MRM) remains the most
      commonly performed surgery for breast cancer today. Conventional surgery using
      scalpel and electrocautery is associated with moderate blood loss and morbidity
      in the form of haematoma, flap necrosis, prolonged axillary drainage, and seroma.
      This study was performed to evaluate the feasibility of using ultrasonic energy
      (harmonic scalpel) for MRM and to standardise the operative technique of harmonic
      scalpel MRM using various available accessories of the harmonic scalpel. METHODS:
      Fourteen patients suffering from carcinoma breast planned for MRM were included
      in the study. RESULTS: The learning curve of harmonic scalpel MRM was short.
      Harmonic scalpel is a multifunctional instrument and the whole operative
      procedure could be accomplished with the currently available accessories. No
      sutures or electrocautery were used. The mean blood loss was 57.5 ml and the mean
      operative time was 117 min. There were no hematomas or flap necroses, whereas one
      patient developed seroma. The mean postoperative drainage volume was 430 ml.
      CONCLUSIONS: In comparison to the historical data of conventional mastectomy,
      there seems to be a reduction in the blood loss and drainage volume using
      harmonic scalpel. Results of our study show that modified radical mastectomy
      using the harmonic scalpel is feasible and the learning curve is short, however,
      further studies are needed to assess the impact on morbidity.

PMID- 10951419
TI  - Cutaneous angiosarcoma in an irradiated breast after breast conservation therapy
      for cancer: association with chronic breast lymphedema.
AB  - The authors report a rare case of cutaneous angiosarcoma arising more than 5
      years after excision of a 1.5 cm invasive ductal cancer of the breast. All lymph
      nodes were negative for metastatic breast cancer in this 68-year-old female. The
      patient had postoperative therapy consisting of 5040 cGy over a 5 week period
      using a 6 Megavolt linear accelerator. After radiation therapy to the breast and
      axillae, the patient developed chronic hard, taut edema of the irradiated right
      breast. Tamoxifen was administered for 5 years and then stopped. Three months
      after the cessation of tamoxifen, cutaneous angiosarcoma was found by skin
      biopsy. A complete mastectomy removed all tumor with clear margins. There are
      less than 60 cases of radiation associated breast angiosarcoma found in the
      literature. The presence of chronic lymphedema in the breast after radiation
      therapy possibly contributes to the development and is an early warning sign for
      later development of secondary angiosarcoma. The characteristic purple nodules
      and discoloration of the irradiated skin is the hallmark to suspect the
      diagnosis. The authors recommend long-term clinical surveillance for this tumor
      for all patients who have received breast conservative surgical therapy with
      concomitant radiation therapy for primary breast cancer.

PMID- 10951420
TI  - Commentary.

PMID- 10951422
TI  - Solitary necrotic nodule of the liver misinterpreted as malignant lesion:
      considerations on two cases.
AB  - In our experience, we document 2 cases of a rare and non-tumoral lesion of the
      liver misinterpreted as necrotic tumor: necrotic solitary nodule. In the first
      clinical case, ultrasound (US) showed a polylobated lesion (35 x 35 x 38 mm) at
      segment 8. Color-doppler identified a compression of celiac axis (Dunbar
      syndrome). Arteriography revealed a subtotal stenosis of celiac tripod soon after
      the emergence of the left gastric artery. FNAB-CT showed a highly cellulated
      tissue with a necrotic core surrounded by a fibersclerotic tissue. The patient
      underwent surgery: cholecystectomy and correction of Dunbar syndrome. US follow
      up showed a progressive reduction in diameter of the lesion (24 x 25 x 25 mm at
      24 months), suggesting in this case the role of ischemic injury in the
      pathogenesis of the lesion. In the second clinical case, a hypoechoic lesion (32
      x 32 x 30 mm) of segment 6 as occasional US finding during the staging for
      prostate cancer was shown. FNAC-CT showed a positive result for necrotic cells.
      Surgical treatment consisted in a wide excision of the lesion. Histologically the
      lesion was solitary necrotic nodule. The diagnosis of this rare lesion is
      accidental. In accordance with the literature (50% of cases), we founded an
      associated tumor. Radiology doesn't differentiate solitary necrotic nodule and
      other solid lesions. Diagnosis is histological (in our second case, FNAC-CT
      misinterpreted the tumor as a malignant lesion, while histology showed the real
      nature of it).

PMID- 10951421
TI  - Combined effects of adeno-associated virus vector and a herpes simplex virus
      mutant as neoplastic therapy.
AB  - BACKGROUND AND OBJECTIVES: Although surgical therapy for pancreatic cancer has
      not been successful, new gene therapies, such as adeno-associated virus (AAV)
      vectors hold promise for treating cancer. However, expression of AAV vectors
      alone is insufficient for adequate effects in vivo for cancer therapy. We
      describe a novel therapy using the combined herpes simplex virus-ICP6 deletion
      mutant (ICP6delta) and AAV vector. METHODS: We investigated ICP6delta and AAV
      regarding kinetics and dose-response relationships of LacZ expression in vitro.
      We studied the expression of LacZ in vivo using subcutaneous pancreatic cancer
      tumors (SW1990) in nude mice. RESULTS: In vitro, ICP6delta enhanced the
      expression of AAV; 24 hr following inoculation there was more expression with AAV
      plus ICP6delta than with AAV plus KOS, and a multiplicity of infection (MOI) of
      0.5 was the optimal titer of ICP6delta to support maximal expression of AAV. In
      vivo, there was much higher expression of LacZ in mice injected with AAV-LacZ
      plus ICP6A than with AAV-LacZ alone. CONCLUSIONS: ICP6delta enhances expression
      of AAV-vector in vitro and in vivo. These results suggested that combined therapy
      have potential for human cancer.

PMID- 10951423
TI  - Celsite port and catheter as an intraperitoneal access device in the treatment of
      ovarian cancer.
AB  - BACKGROUND AND OBJECTIVES: In ovarian cancer, development of safe and effective
      methods for providing long-term access to the peritoneal cavity has become
      increasingly important. METHODS: A modified Port-A-Cath (Celsite-port and
      catheters, B. Braun, Chasseneuil, France) was used in 56 patients with presumed
      epithelial ovarian cancer at the conclusion of primary or second-look laparotomy.
      In 37 patients, ports were located on the right costal margin in the
      midclavicular region and in 19 in the xiphoid region. RESULTS: In 56 catheters, 8
      (13.8%) complications of severe or moderate degree during the treatment were
      registered. In-flow obstruction of device occurred in 6 patients, and there was 1
      viscous perforation and 1 catheter related infectious peritonitis. Grade III-IV
      pain and in-flow obstruction were developed in the patients with ports implanted
      on the right costal margin but not with ports implanted in the xiphoid region.
      CONCLUSION: The complication rate of intraperitoneal access devices is
      comparatively low.

PMID- 10951424
TI  - Surgical treatment for recurrent hepatocellular carcinoma with tumor thrombi in
      right atrium: using cardiopulmonary bypass and deep hypothermic circulatory
      arrest.
AB  - Tumor in the right atrium creates a life-threatening condition and should be
      removed immediately. A cirrhotic patient who had recurrent hepatocellular
      carcinoma (HCC) over remnant liver with tumor thrombi extending to inferior vena
      cava (IVC) and right atrium presented with impending congestive heart failure.
      The recurrent tumor and its thrombi were successfully resected en-bloc using
      cardiopulmonary bypass and hypothermic circulatory arrest. Although the patient's
      disease-free and actual survival time were only 6 months and 14 months,
      respectively, he was rescued from heart failure. This aggressive surgical
      strategy creates further possibility to treat such advanced HCC cases. Further
      investigations regarding adjuvant therapies in these circumstances, however, are
      necessary.

PMID- 10951425
TI  - Menses and breast cancer: does timing of mammographically directed core biopsy
      affect outcome?
AB  - BACKGROUND AND OBJECTIVES: Studies have shown molecular, genetic and cellular
      changes in breast cancer during the menstrual cycle. Changes in proliferative and
      metastatic potential of breast cancer cells during menses could explain improved
      survival when tumors are surgically removed in the luteal phase. This study
      examined if timing of mammography/core biopsy (MAM-CB) also affected breast
      cancer prognosis (histological tumor grade). METHODS: Eighty-five premenopausal
      women undergoing MAM-CB at one clinic between March 1995 and February 1998 were
      retrospectively studied. All patients had Stage I or II breast cancer surgically
      treated. Patients were grouped by phase of menses at MAM-CB: follicular (F, Days
      0-14) or luteal (L, Days 15-35). Groups were comparable in age, menarche, family
      history, nulliparity, breastfeeding, and total percentage of clinically palpable
      tumors. Pathological characteristics of the tumors (tumor size, tumor type,
      estrogen and progesterone receptor status, axillary lymph node status, the
      presence of lymphatic or vascular invasion and extranodal metastasis) was also
      comparable across the 2 groups. RESULTS: Low-grade tumors were more frequent in
      the MAM-CB group L, whereas high-grade tumors were more common in the MAM-CB
      group F (P = 0.002, chi2(4) = 17.06). CONCLUSIONS: Timing of MAM-CB in relation
      to menses may be a factor influencing breast cancer outcome. Future studies
      examining the effect of menses on the outcome of breast cancer should consider
      the potential effect of the timing of MAM-CB.

PMID- 10951426
TI  - Menstrual cycle and breast cancer.

PMID- 10951427
TI  - Rhythmic menstrual cycle modulation of breast cancer biology.

PMID- 10951429
TI  - Oligonucleotide transport in rat and human intestine ussing chamber models.
AB  - Cellular and intestinal absorption of naked oligonucleotides (ONs) is limited and
      still remains a developmental challenge. A previous report in the literature
      suggests that ON absorption occurs via a paracellular mechanism. The aim of this
      study was to test this hypothesis using rat and human intestine in a Ussing
      chamber and in Caco-2 cells. Transport of a (35)S-labelled mixed backbone ON
      (MBO) across human or rat intestinal tissue or across Caco-2 cells was measured
      after a 2-h incubation in the presence or absence of increasing MBO
      concentrations or with uptake inhibitors and enhancers. MBO intestinal absorption
      was compared with an internal standard, mannitol. (35)S-MBO demonstrated very
      little absorption (<1%) across rat and human intestinal tissues. Transport
      appeared to be unsaturable up to 500 microM, and relatively insensitive to
      compounds that opened tight junctions or inhibited P-glycoprotein. However,
      preliminary studies with Caco-2 cells suggest a possible saturable mechanism at
      higher ON concentrations. Confocal fluorescence microscopy studies show that
      fluorescein isothiocyanate (FITC)-MBO was internalized into intestinal cells.
      Although some differences in ON transport were observed as a function of the
      transport model, MBO transport was mostly consistent with a transcellular, rather
      than a paracellular, absorption mechanism.

PMID- 10951428
TI  - Bioequivalence evaluation of lomefloxacin 400 mg tablets (Lomax versus Maxaquin
      in healthy human volunteers.
AB  - This study represents the results of a randomized, single dose, two-treatment,
      two-period crossover study in 18 healthy male volunteers to assess the
      bioequivalence of two tablets of 400 mg lomefloxacin. The two formulations were:
      Lomax(R) (Julphar, United Arab Emirates) as the test formulation and Maxaquin(R)
      (Searle, S.A., UK) as the reference formulation. The study was conducted at the
      College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with
      King Khalid University Hospital, Riyadh, Saudi Arabia. After overnight fasting
      the two products were administered as a single dose on two treatment days
      separated by a 1 week washout period. Serial blood samples were collected
      thereafter, for a period of 48 h. Plasma harvested from blood was analysed for
      lomefloxacin by a sensitive, reproducible and accurate HPLC method. Various
      pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max,) T(max),
      T(1/2), K(elm) and C(max)/AUC(0-infinity) were determined from plasma
      concentrations for both formulations and found to be in good agreement with
      reported values. Statistical modules applied to AUC(0-t), AUC(0-infinity) and
      C(max) revealed no significant difference in the two tested products. Based on
      these statistical inferences it was concluded that Lomax(R) is bioequivalent to
      Maxaquin(R).

PMID- 10951431
TI  - Pharmacokinetics of cisplatin in analbuminemic rats.
AB  - The effect of protein binding on the pharmacokinetics of cisplatin (cis
      diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats,
      which genetically lack albumins, in comparison with normal rats. CDDP was
      reported to highly bind to serum components, and the major binder was thought to
      be an albumin. However, there were no significant differences in the serum
      disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP
      to analbuminemic rats as compared with normal rats. The total body clearance,
      Cl(tot), of platinum in normal rats was 48.7+/-22.0 mL h(-1) (5 mg kg(-1)),
      55.9+/-4.04 mL h(-1) (10 mg kg(-1)) and 49.0+/-3.57 mL h(-1) (20 mg kg(-1)),
      whereas Cl(tot) in analbuminemic rats was 52.0+/-8.48 mL h(-1) (5 mg kg(-1)),
      62.9+/-10. 8 mL h(-1) (10 mg kg(-1)) and 62.8+/-6.81 mL h(-1) (20 mg kg(-1)). The
      serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection
      were higher in both groups of rats who received CDDP than those of pre-dose
      level. However, there were no significant differences in the renal function tests
      between analbuminemic rats and normal rats. The binding of CDDP to the serum
      samples obtained from analbuminemic rats and normal rats was measured by a
      centrifuging filtration method. The binding percentages were 68.0+/-5.9% (2.0
      microg mL(-1)), 56.8+/-4.1% (5.0 microg mL(-1)) and 64.6+/-4.4% (10.0 microg mL(
      1)) in analbuminemic rats and 52.9+/-3.5% (2.0 microg mL(-1)), 52.2+/-3.4% (5.0
      microg mL(-1)), 56.9+/-1.9% (10.0 microg mL(-1)) in normal rats. Higher binding
      percentages were obtained in analbuminemic rats than in normal rats. In vitro
      binding studies under the two incubation conditions (5 min and 2 h) showed that
      the binding percentages of CDDP to serum proteins were 59.2+/-3.2% (5 min) and
      72.3+/-6.5% (2 h) for albumin, 42.3+/-1.9% (5 min) and 39.5+/-2.5% (2 h) for
      alpha(1)-acid glycoprotein (AAG) and 51.7+/-5.3% (5 min) and 49. 2+/-1.9% (2 h)
      for gamma-globulin. From these studies, it was elucidated that albumin is not the
      major ligand in the rat serum and that other proteins also have important roles
      in the pharmacokinetics of CDDP.

PMID- 10951430
TI  - Bioequivalence of immediate-release theophylline capsules.
AB  - A three-way crossover study in 18 healthy male volunteers was conducted to
      evaluate the bioequivalence of three different 200 mg anhydrous theophylline
      immediate-release (IR) capsules. The products had not been rated as
      therapeutically equivalent by the US Food and Drug Administration (FDA) owing to
      a lack of bioequivalence data. Serum samples were obtained from 0 to 34 h after
      dosing. Mean time of maximum serum concentration (T(max)) ranged from 1.3 to 1.4
      h. Mean values for the maximum serum concentration (C(max)) and the area under
      the serum concentration-time curves (AUC) differed by <5% for the three products.
      The confidence limits for Ln-transformed C(max) and AUC ranged from >/=89 to
      </=113%. It was concluded that the three products were bioequivalent. In
      addition, the rapid in vitro dissolution of these formulations, as well as the
      reported high solubility and high permeability of theophylline, was predictive of
      the lack of any bioavailability differences among the three products.

PMID- 10951432
TI  - Pharmacokinetics of ezlopitant, a novel non-peptidic neurokinin-1 receptor
      antagonist in preclinical species and metabolite kinetics of the
      pharmacologically active metabolites.
AB  - The pharmacokinetics of ezlopitant were determined in the rat, gerbil, guinea
      pig, ferret, dog and monkey after intravenous and oral administration. In
      general, ezlopitant is marked by high clearance values that approach or exceed
      hepatic blood flow values, moderate to high values for steady-state volume of
      distribution (3. 9-28 L/kg), and terminal phase half-life values ranging from 0.6
      h in the guinea pig to 7.7 h in the rat. Oral bioavailability ranged from <0.2%
      (guinea pig) to 28% (dog). Data from portal vein cannulated dogs suggested that
      37% of an oral dose of ezlopitant enters the portal vein as an unchanged drug in
      this species. Ezlopitant is metabolized to two pharmacologically active
      metabolites, an alkene (CJ-12 458) and a benzyl alcohol (CJ-12 764). After
      administration of the parent compound, CJ-12 764 was found in greater abundance
      than CJ-12 458 in all species examined. Ezlopitant and CJ-12 458 were highly
      protein bound in plasma (or serum), whereas the protein binding of CJ-12 764 was
      somewhat lower. Measurement of the kinetics of ezlopitant, CJ-12 458 and CJ-12
      764 in the cerebrospinal fluid (CSF) of dogs demonstrated that all three
      compounds can partition into the CSF, and thereby, be capable of contributing to
      centrally mediated pharmacological effects. Thus, these data suggest that the
      pharmacological activity exhibited by ezlopitant in preclinical species in vivo
      is likely a result of the parent compound plus the active metabolites.
      Furthermore, the contributions of ezlopitant and the active metabolites to
      pharmacological activity probably varies with the identity of the model species,
      as well as the dose and route of ezlopitant administration.

PMID- 10951433
TI  - Facts and fancies on writer's cramp.

PMID- 10951434
TI  - Insights into muscle diseases gained by phosphorus magnetic resonance
      spectroscopy.
AB  - Phosphorus magnetic resonance spectroscopy (P-MRS) has now been used in the
      investigation of muscle energy metabolism in health and disease for over 15
      years. The present review describes the basics of the metabolic observations made
      by P-MRS including the assumptions and problems associated with the use of this
      technique. Extramuscular factors, which may affect the P-MRS results, are
      detailed. The important P-MRS observations in patients with mitochondrial
      myopathies, including the monitoring of experimental therapies, are emphasized.
      The findings in other metabolic myopathies (those associated with glycolytic
      defects or endocrine disturbances) and in the destructive myopathies (the
      dystrophies and the inflammatory myopathies) are also described. Observations
      made in normal and abnormal fatigue, fibromyalgia, and malignant hyperthermia are
      considered. Finally, a summary of the possible diagnostic use of P-MRS in
      exercise intolerance is provided.

PMID- 10951435
TI  - Postcontraction depression of reciprocal inhibition in human forearm muscles.
AB  - We tested whether a preceding muscle contraction changes reciprocal inhibition
      (RI) between forearm antagonists. RI was studied in 14 healthy subjects by
      assessing changes in the H reflex (evoked by median-nerve stimulation) in forearm
      flexor muscles after conditioning radial-nerve stimulation at 0- and 20-ms
      intervals. The maximum sizes of the M wave (M(max)) and H reflex (H(max)) were
      also measured. After a long-lasting maximum voluntary handgrip contraction (mean
      +/- SEM: 3.9 +/- 0.6 min) of ipsilateral forearm muscles, M(max) and H(max) were
      unchanged but RI was diminished. After contraction of the contralateral
      homologous muscles and after contraction elicited by ipsilateral muscle
      stimulation, RI remained unchanged. These results show that a preceding maximum
      voluntary contraction (lasting 30 s or more) reduces the activity of the spinal
      inhibitory interneurons mediating RI. This finding may imply the need to
      reinterpret results from RI studies in normal subjects and in patients with
      movement disorders.

PMID- 10951436
TI  - A multicenter, double-blind, randomized trial of deflazacort versus prednisone in
      Duchenne muscular dystrophy.
AB  - We randomized 18 Duchenne muscular dystrophy (DMD) boys whose age ranged from 5.2
      to 14.6 years (mean, 7.3 years) for treatment with either deflazacort (0.9
      mg/kg/day) or prednisone (0.75 mg/kg/day) on the basis of age and functional
      score at the onset of treatment. We followed the patients every 3 months for 1
      year, evaluating four limb muscles with the Medical Research Council scale and
      performance of four functions (walking, climbing stairs, Gowers' maneuver, and
      rising from a chair). Side effects were monitored by a questionnaire and by
      routine blood examination, and weight and height were recorded at each visit. At
      12 months, the effect of both steroids was examined by comparing the status of
      the treated patients with another group of untreated DMD patients that served as
      natural history control. The two steroids were equally effective in improving
      motor function and functional performances. At 9 months, the average weight
      increase with respect to baseline value was 5% (2 kg) in the deflazacort group
      but 18% in the prednisone group (P < 0. 005), and the change remained significant
      after 12 months (P < 0.05). Other minor but nonsignificant side effects were
      observed. Steroid treatment with deflazacort appears to cause fewer side effects
      than with prednisone, particularly weight gain, which could be important to
      maximize motor performances.

PMID- 10951437
TI  - Muscle fatigue induced by stimulation with and without doublets.
AB  - Muscles are usually stimulated by shocks delivered at some constant rate.
      However, human thenar motor units generate optimum force per pulse when excited
      by impulse trains that begin with one or two short interpulse intervals
      ("doublets"), followed by longer intervals. Our aim was to determine whether the
      rate of force and force-time integral reduction during fatigue of thenar muscles
      is influenced by an initial doublet, and/or the number of pulses per train. We
      first matched thenar force-time integral using two different pulse patterns, one
      of which began with a doublet. Fatigue induced by trains that contained a doublet
      resulted in slower rates of force and force-time integral reduction and smaller
      increases in half-relaxation time than that evoked by bursts of 40-HZ
      stimulation. When the force was measured in each protocol after equal numbers of
      pulses had been delivered, the force loss was still significantly less for pulse
      trains containing a doublet. These results have useful implications when
      designing stimulation to strengthen weak muscles or to drive paralyzed muscles.

PMID- 10951438
TI  - Effects of LIF dose and laminin plus fibronectin on axotomized sciatic nerves.
AB  - Leukemia inhibitory factor (LIF), a cytokine which has neurotrophic and
      myotrophic activities, has been shown to enhance nerve regeneration and
      consequent return of muscle function in the entubulation model of sciatic nerve
      repair. Fibronectin (FN) and laminin (LN) are two extracellular matrix (ECM)
      components that, when combined, promote axon growth in the entubulation model.
      The aim of this study was to determine the optimal LIF dose and the efficacy of
      FN plus LN administered either alone or simultaneously with the optimal LIF dose.
      We found that at 12 weeks following nerve repair, a single 10 ng LIF dose
      produced the largest medial gastrocnemius (MG) muscle mass (P < 0.0001) and
      maximum force contraction (P < 0.001). The diameter of the axons in the FN plus
      LN group were significantly greater than for saline (P < 0.001) and the LIF dose
      groups (P < 0.01). When 10 ng LIF was combined with FN plus LN, the MG muscle
      mass was significantly greater than the optimal LIF dose (P < 0.05), suggesting
      an additive effect. Our findings support the view that combinations of factors,
      which perhaps act on complementary mechanisms for nerve regeneration, will be
      required to maximally potentiate nerve regeneration and return of muscle function
      after nerve injury.

PMID- 10951439
TI  - Excitability properties of median and peroneal motor axons.
AB  - Threshold tracking was used to compare excitability properties (stimulus-response
      curves, strength-duration properties, recovery cycle, and threshold electrotonus)
      of median motor axons at the wrist and peroneal motor axons at the ankle in 12
      healthy subjects. Stimulus-response curves and strength-duration properties were
      similar, though higher stimulus intensities were required for peroneal axons.
      However, there were significant differences in the recovery cycle of excitability
      following a conditioning stimulus and in threshold electrotonus. In the recovery
      cycle, median axons had significantly greater supernormality and late
      subnormality. In threshold electrotonus, the initial slow threshold changes in
      response to subthreshold depolarizing and hyperpolarizing currents (S1) were
      significantly greater in median axons, and there was also greater accommodation
      to depolarizing currents (S2) and greater threshold undershoot after
      depolarization. Similar differences in supernormality and the S1 phase of
      threshold electrotonus were found between peroneal axons at ankle and knee,
      suggesting that these properties may be dependent on nerve length. When median
      motor axons at the wrist were compared with peroneal motor axons at the knee,
      there were no differences in refractoriness and supernormality and only small
      differences in S1, but the late subnormality and undershoot were significantly
      greater in the median axons. These findings suggest that, in addition to any
      length-dependent differences, peroneal axons have a less prominent slow K(+)
      conductance. We conclude that the properties of different motor axons are not
      identical and their responses to injury or disease may therefore differ.

PMID- 10951440
TI  - Helix-loop-helix transcription factors in electrically active and inactive
      skeletal muscles.
AB  - The muscle-specific helix-loop-helix (HLH) transcription factors myoD, myogenin,
      MRF4, and myf-5 are called the muscle regulatory factor family (MRF). Levels of
      MRFs are strongly regulated by muscle electrical activity and are thought to
      control downstream genes that are important for muscle phenotype such as the
      acetylcholine receptor (AChR) and possibly genes connected to muscle metabolic
      properties. The MRFs interact with ubiquitously expressed HLH factors such as E
      proteins and Id-proteins to form heterodimers. In the present paper, we report
      the effects of paralysis obtained by nerve impulse block with tetrodotoxin (TTX)
      and denervation on messenger ribonucleic acid (mRNA) levels for Id-1, E47,
      myogenin, AChR alpha-subunit and beta-actin. Both Id-1 and E47 showed twofold
      increases in absence of nerve evoked electrical activity. These changes in the
      ubiquitously expressed HLH factors might have important functional implications
      for downstream gene expression, but in comparison, myogenin mRNA was increased 10
      fold. We conclude that myogenin and the other muscle-specific MRFs remain the
      transcription factors with the strongest activity dependence that has so far been
      described in muscle.

PMID- 10951441
TI  - Limb immobilization alters muscle activation patterns during a fatiguing
      isometric contraction.
AB  - The purpose of the study was to determine the role of excitation-contraction
      coupling in the increased endurance time for low-force contractions after 4 weeks
      of elbow joint immobilization. Twelve subjects participated in a protocol that
      required immobilization of the elbow joint in a fiberglass cast for 4 weeks, and
      4 subjects acted as controls. Measurements of muscle strength, contractile
      properties, and fatigability were performed before and after 4 weeks of limb
      immobilization, and after 4 weeks of recovery. The immobilization intervention
      produced significant reductions in the daily activity of the elbow flexor
      muscles, a 21% decline in the maximum voluntary contraction (MVC) force, and a
      31% decrease in the maximum load that could be lifted once. Seven of the
      immobilized subjects exhibited an unusual pattern of muscle activity during the
      fatiguing contraction after immobilization, which was associated with an increase
      in the endurance time of the elbow flexor muscles (mean = 220%) in these
      subjects. The unusual pattern of muscle activity involved lower relative activity
      of the brachialis muscle, no increase in the amplitude of the electromyogram
      (EMG) for the elbow flexor muscles, and intermittent rather than continuous EMG.
      In contrast, the force-frequency relationship of biceps brachii was not altered
      by immobilization in these subjects, suggesting that adaptations in excitation
      contraction coupling were not the primary cause of the prolonged endurance time
      after immobilization. Rather, the results suggest that the prolonged endurance
      time exhibited by some subjects after immobilization was largely due to
      adaptations within the nervous system.

PMID- 10951442
TI  - Assessing grip strength in healthy individuals and patients with immune-mediated
      polyneuropathies.
AB  - Grip strength reference values for a portable dynamometer, the hand-held
      Vigorimeter, were calculated, and its validity, reliability, and responsiveness
      were examined in patients with immune-mediated polyneuropathies. We studied 530
      healthy controls (age 5-93 years), 113 patients with stable polyneuropathy (83
      with Guillain-Barre syndrome [GBS], 22 with chronic inflammatory demyelinating
      polyneuropathy [CIDP], and 8 with a gammopathy-associated polyneuropathy), and 20
      patients with GBS or CIDP and changing clinical conditions (longitudinal group).
      An arm-disability scale was also assessed. Grip-strength reference values were
      calculated depending primarily on age and gender. Significant association was
      obtained between the Vigorimeter and the arm scale (in stable group, Spearman
      rank: r = -0.52 to -0.62; P </= 0.0005; in longitudinal group, linear
      regressions: r = 0.62-0.64, P < 0.0001). Good interobserver and intra-observer
      agreements (analysis of variance, r = 0.95-0.97) and high responsiveness
      (standardized response mean scores > or = 0.8) were demonstrated for the
      Vigorimeter. These results emphasize the clinical usefulness of the Vigorimeter,
      particularly in patients with immune-mediated polyneuropathies.

PMID- 10951443
TI  - Fatigue and its impact on patients with myasthenia gravis.
AB  - We have examined fatigue in myasthenia gravis (MG) by administering a measure of
      cognitive and physical fatigue to patients and control subjects before and after
      administration of a lengthy cognitive battery. Subjects also completed a scale
      that assessed the impact of fatigue on physical, social, and cognitive function.
      Results of the study revealed that MG patients experience significantly more
      cognitive and physical fatigue than do control subjects, and the patients'
      perceptions of both cognitive and physical fatigue increased significantly
      following completion of demanding cognitive work. Control subjects reported no
      significant change in fatigue. Furthermore, MG patients reported that fatigue
      produced mild to moderate effects on cognitive and social function and moderate
      effects on physical function. Results from this study indicate that cognitive
      fatigue is an important symptom of MG and that fatigue produces pervasive
      impairments in important aspects of patients' lives. Additional studies are
      needed to understand the neurobehavioral determinants of cognitive fatigue in
      this population.

PMID- 10951444
TI  - Cruzipain induces autoimmune response against skeletal muscle and tissue damage
      in mice.
AB  - The goal of the current study was to investigate whether cruzipain, a major
      Trypanosoma cruzi antigen, is able to induce in mice an autoimmune response and
      skeletal muscle damage. We demonstrate that immunization with cruzipain triggers
      immunoglobulin G antibody binding to a 210-kDa antigen from a syngeneic skeletal
      muscle extract. The absorption of immune sera with purified myosin completely
      eliminated this reactivity, confirming that the protein identified is really
      myosin. We also found that spleen cells from immunized mice proliferated in
      response to a skeletal muscle extract rich in myosin and to purified myosin.
      Cells from control mice did not proliferate against any of the antigens tested.
      In addition, we observed an increase in plasma creatine kinase activity, a
      biochemical marker of muscle damage. Histological studies showed inflammatory
      infiltrates and myopathic changes in skeletal muscle of immunized animals.
      Electromyographic studies of these mice revealed changes such as are found in
      inflammatory or necrotic myopathy. Altogether, our results suggest that this
      experimental model provides strong evidence for a pathogenic role of
      anticruzipain immune response in the development of muscle tissue damage.

PMID- 10951445
TI  - Anti-GM1 antibodies can block neuronal voltage-gated sodium channels.
AB  - Anti-GM1 antibodies, frequently found in the serum of patients with Guillain
      Barre syndrome (GBS), have been suggested to interfere with axonal function. We
      report that IgG anti-GM1 antibodies, raised in rabbits, can reversibly block the
      voltage-gated Na(+) channels of nerve cells, thus causing a reduction of the
      excitatory Na(+) current. The block was, however, only substantial when the
      antibodies were applied together with rabbit complement factors. A solution
      containing anti-GM1 sera (dilution 1:100) and complement (1:50) reduced the Na(+)
      current to 0.5 +/- 0.2 times control (mean value +/- SD). Applications of the
      antibody by itself, complement by itself, or anti-GM2 or anti-GM4 antibodies
      (1:100) plus complement had little effect. The complexes of anti-GM1 antibodies
      and complement factors block the ion-conducting pore of the channel directly. In
      addition, they increase the fraction of channels that are inactivated at the
      resting potential and alter channel function by changing the membrane surface
      charge. The described effects may be responsible for conduction slowing and
      reversible conduction failure in some GBS patients.

PMID- 10951446
TI  - Reduced expression of DMAHP/SIX5 gene in myotonic dystrophy muscle.
AB  - In myotonic dystrophy (DM), the expansion of CTG triplet repeats in the 3'
      untranslated region of DM-protein kinase (DMPK) is a causal gene mutation.
      However, the pathogenic molecular mechanism of CTG repeat expansion for DM
      phenotypic expression is unclear. To investigate this issue, we examined the
      influence of CTG repeat expansion on the expression levels of DMPK gene and 3'
      flanking DM locus-associated homeodomain protein (DMAHP)/SIX5 gene in the muscles
      of DM patients. We isolated RNA from muscle tissues of six DM patients and six
      controls, and performed a competitive reverse transcriptional polymerase chain
      reaction (RT-PCR) assay. The total mRNA level of DMAHP/SIX5 was significantly
      lower in DM than in controls, but the DMPK mRNA level was unchanged. Our results
      suggest that CTG repeat expansion influences the expression of genes other than
      DMPK to cause the DM phenotype.

PMID- 10951447
TI  - Limits of the sympathetic skin response in patients with diabetic polyneuropathy.
AB  - We performed upper- and lower-limb sympathetic skin responses (SSRs) in a series
      of 337 diabetic patients with and without peripheral polyneuropathy and 38
      reference subjects. We did not find any correlations between SSRs and symptoms of
      pain or autonomic dysfunction. The SSR correlated more strongly with vibration
      perception threshold (VPT) and sural nerve amplitude than with cooling detection
      threshold (CDT) or clinical symptoms. We conclude that current limitations
      inherent in SSR testing preclude its use as a reliable and consistent index of
      the autonomic dysfunction commonly encountered in diabetic patients.

PMID- 10951448
TI  - Magnetic resonance imaging of denervated muscle: comparison to electromyography.
AB  - The purpose of the study is to further assess the usefulness of short TI (time to
      inversion) recovery (STIR) magnetic resonance imaging (MRI) in detecting
      denervation of skeletal muscle compared to needle electromyography (EMG). Ninety
      subjects with clinical evidence of peripheral nerve injury or radiculopathy
      underwent STIR MRI and EMG of the affected limb. In 74 (82%) of these subjects, a
      positive correlation was found between STIR MRI and EMG (P < 0.009). STIR MRI has
      a relative sensitivity of 84% and specificity of 100% for detecting denervation.
      A subset of 28 subjects underwent quantitative assessments of signal intensity
      ratio (SIR) from the STIR MRI. The rank order correlation coefficient between the
      SIR and abnormal spontaneous activity on EMG was 0.70 (P < 0.001). Increased
      signal intensity on STIR MRI corresponds closely with spontaneous activity on EMG
      in denervated muscle. Although less sensitive than EMG in detecting muscle
      denervation, STIR MRI may be a useful adjunctive diagnostic tool in this setting.

PMID- 10951449
TI  - Blink reflexes and the silent period in tetanus.
AB  - Abnormalities of the silent period (SP) and blink reflexes occur in diseases that
      interfere with inhibitory pathways, such as tetanus and stiff-person syndrome
      (SPS). The SP is abnormal in tetanus but not in SPS. Studies of the blink reflex
      in tetanus are limited. In this report, a patient with generalized tetanus is
      described. The masseteric-and mixed-nerve SP was absent or truncated. In contrast
      to SPS, blink reflex studies revealed no bilateral R1 component, and a discrete
      R3 was only present ipsilateral to right supraorbital stimulation. This reflects
      the distinct inhibitory pathways underlying these disorders.

PMID- 10951450
TI  - Recurrent idiopathic lumbosacral plexopathy.
AB  - Recurrent idiopathic lumbosacral plexopathy has rarely been reported in the
      literature. The present report describes a 59-year-old man presenting with
      recurrent episodes of acute leg pain, followed by weakness. After each episode,
      symptoms progressed for several months before peaking. Thereafter, gradual
      recovery ensued. Electrodiagnostic studies revealed primarily a patchy pattern of
      denervation in the distribution of part of the lumbosacral plexus, sparing the
      paraspinal muscles. Extensive evaluations for an underlying cause were
      unrevealing. Thus, these episodes are suggestive of recurrent idiopathic
      lumbosacral plexopathy, and the present case is compared with previous cases
      reported in the literature.

PMID- 10951451
TI  - The role of electrodiagnostic technologists in the operating room.

PMID- 10951452
TI  - Identification of cranial nerve nuclei.

PMID- 10951453
TI  - Reply

PMID- 10951454
TI  - AAEM news and comments

PMID- 10951455
TI  - Novel ring chromosome composed of X- and Y-derived material in a girl with
      manifestations of Ullrich-Turner syndrome.
AB  - We present a female infant who has a novel genetic variant of Ullrich-Turner
      syndrome. Chromosome analysis on amniotic fluid cells obtained because of
      ultrasound observation of nuchal thickening showed 45,X in all cells. The infant
      was born with a low posterior hairline and moderate edema over hands and feet.
      Postnatal chromosome analysis demonstrated two cell lines-47% of the metaphases
      were 45,X, but 53% had a ring chromosome in addition to the normal X. FISH
      studies using alpha satellite probes, an X-whole-chromosome-paint (WCP) probe,
      and a Y-cocktail probe determined that the ring was composed of both X and Y
      sequences. FISH studies also determined that the KAL locus was present on the
      ring, but that XIST was absent. PCR-based analysis of lymphocyte DNA documented
      that the ring contained sequences from both the short and the long arm of the Y
      chromosome. X-chromosome analysis using a panel of highly polymorphic markers
      indicated that the ring contained material derived only from Xp22.1 to Xp21.3. No
      Xq material was identified on the ring, and androgen receptor-based X
      inactivation studies suggested that the intact X chromosome was not subject to
      random X inactivation.

PMID- 10951456
TI  - Subtelomeric familial translocation t(2;7)(q37;q35) leading to partial trisomy
      7q35-->qter: molecular cytogenetic analysis and clinical phenotype in two
      generations.
AB  - Few patients with trisomy of the most distal region of chromosome 7q have been
      described. We report on a familial translocation t(2;7)(q37;q35) leading to
      trisomy 7q35-->7qter in a child and her paternal uncle and a minimal deletion of
      distal 2q as demonstrated by FISH with probes located in the chromosome 2q
      subtelomeric region. The clinical phenotype included macrocephaly and low-set
      ears, also found in other reported patients trisomic for the distal part of
      chromosome 7q. Phenotypic findings probably useful for the clinical diagnosis
      include normal size at birth, large head with frontal bossing, low-set ears of
      normal shape, small nose and low nasal bridge, feeding difficulties in infancy,
      and severe neurodevelopmental delay.

PMID- 10951457
TI  - Isolated small intestinal atresias in Latin America and Spain: epidemiological
      analysis.
AB  - Stenosis, atresia, or absence of part of the duodenum, jejunum, or ileum are
      generally considered small intestinal atresias (SIAs). SIAs occur as isolated
      defects, in combination with other unrelated congenital anomalies, or as part of
      syndromes. We performed an epidemiological study of infants with isolated SIAs
      using data from two large congenital defects registries, one from Latin America
      (ECLAMC) and the other from Spain (ECEMC). The overall prevalence of SIAs is
      similar in both programs, being 1.32 per 10,000 livebirths in Spain and 1.29 per
      10.000 livebirths in Latin America. Our results suggest that infants with
      isolated SIAs are characterized epidemiologically on the basis of shorter
      gestational age and low birthweight, an association with twinning, the parents
      are more frequently consanguineous, and their pregnancies are more frequently
      complicated by vaginal bleeding. The results also suggest an association between
      some maternal infections and ileal atresia. The fact that these characteristics
      have been observed in children with these types of anomalies occurring in
      different geographical areas and populations supports the conclusion that these
      characteristics are causally related to these defects.

PMID- 10951458
TI  - Cholesterol supplementation with egg yolk increases plasma cholesterol and
      decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition comprising
      multiple malformations, mental retardation, and growth failure, results from
      reduced activity of the final enzyme in cholesterol biosynthesis, 7
      dehydrocholesterol Delta(7)-reductase (DHCR7). Reduced plasma and tissue
      cholesterol concentrations and accumulation of cholesterol precursors including 7
      dehydrocholesterol (7-DHC) are characteristic biochemical abnormalities. While it
      is still unclear what role these potentially toxic precursors have in the
      pathogenesis of this disorder, the accumulation of 7-DHC in the brain has been
      associated with impaired learning in rats and oxidized 7-DHC has been shown to
      induce growth retardation in cultured rat embryos. We hypothesized that
      supplemental dietary cholesterol would increase plasma cholesterol levels and
      suppress synthesis of 7-DHC and other abnormal sterols in individuals with SLOS.
      After baseline sterol levels were obtained, patients were provided supplemental
      cholesterol as egg yolk. Plasma sterols were analyzed by capillary-column gas
      chromatography over time in four children with SLOS. When evaluated at 4-8 weeks
      after the initiation of cholesterol supplementation, there was a marked increase
      in mean plasma cholesterol, from 53 mg/dl to 82 mg/dl. While the percent of total
      sterols as 7-DHC decreased from 15% to 10%, there was no change in total plasma 7
      DHC levels. However, when evaluated 35-90 weeks after the institution of
      cholesterol supplementation, mean plasma 7-DHC decreased, from 11.3 mg/dl to 3.5
      mg/dl (-67%, P < 0.05), along with an increase in mean plasma cholesterol from 53
      mg/dl to 114 mg/dl (+116%, P < 0.05). These results support the hypothesis that
      over time dietary cholesterol supplementation from egg yolk increases the plasma
      cholesterol levels and decreases levels of 7-DHC which may be toxic. These data
      have important therapeutic implications in the management of SLOS.

PMID- 10951459
TI  - Association between presenilin-1 polymorphism and maternal meiosis II errors in
      Down syndrome.
AB  - Several lines of evidence suggest a shared genetic susceptibility to Down
      syndrome (DS) and Alzheimer disease (AD). Rare forms of autosomal-dominant AD are
      caused by mutations in the APP and presenilin genes (PS-1 and PS-2). The
      presenilin proteins have been localized to the nuclear membrane, kinetochores,
      and centrosomes, suggesting a function in chromosome segregation. A genetic
      association between a polymorphism in intron 8 of the PS-1 gene and AD has been
      described in some series, and an increased risk of AD has been reported in
      mothers of DS probands. We therefore studied 168 probands with free trisomy 21 of
      known parental and meiotic origin and their parents from a population-based
      material, by analyzing the intron 8 polymorphism in the PS-1 gene. An increased
      frequency of allele 1 in mothers with a meiosis II error (70.8%) was found
      compared with mothers with a meiosis I error (52.7%, P < 0.01), with an excess of
      the 11 genotype in the meiosis II mothers. The frequency of allele 1 in mothers
      carrying apolipoprotein E (APOE) epsilon4 allele (68.0%) was higher than in
      mothers without epsilon4 (52.2%, P < 0.01). We hypothesize that the PS-1 intronic
      polymorphism might be involved in chromosomal nondisjunction through an influence
      on the expression level of PS-1 or due to linkage disequilibrium with
      biologically relevant polymorphisms in or outside the PS-1 gene.

PMID- 10951460
TI  - Segregation analysis of asthma: recessive major gene component for asthma in
      relation to history of atopic diseases.
AB  - Although asthma has a significant heritable component, the mode of inheritance
      remains controversial because of the complexity of the disease and the influence
      of environmental factors. Segregation analysis for asthma are performed with and
      without a history of atopic diseases (dermatitis and rhinitis) after adjusting
      for environmental factors. To investigate whether asthma may be inherited through
      a major gene with two alleles, the REGD program of the Statistical Analysis for
      Genetic Epidemiology (SAGE) package was conducted in 1,990 individuals from 227
      families with at least one asthmatic child in a cross-sectional study of
      respiratory diseases in Southern Taiwan. Other covariates adjusted for included
      age, sex, current smoking, and environmental tobacco smoking. The hypothesis of
      Mendelian model and no parent-offspring transmission was rejected. However, when
      the variables of atopic disease and environmental factors were included in the
      model as covariates, the models for a two-allele gene with a recessive or
      codominant inheritance could not be rejected, and Akaike's Information Criterion
      was smaller (1,377. 13) for the recessive model than all of the other models
      tested, assuming a major gene with a population frequency of 0.56 +/- 0.04.
      However, Mendelian model without family effect was rejected. In conclusion, a
      history of asthma in parents is a strong risk factor for asthma in offspring.
      Under the assumptions of the applied segregation, at least one major gene exists
      that could be a gene involved also in allergy. However, the data suggest that a
      single locus gene explains a portion of asthma that is related to the history of
      atopic diseases. In addition, a polygenic/multifactorial (genetic and
      environmental factors) influence with a recessive component inheritance may be
      involved in the pathogenesis of asthma.

PMID- 10951461
TI  - Search for imprinted regions on chromosome 14: comparison of maternal and
      paternal UPD cases with cases of chromosome 14 deletion.
AB  - Over the past few years, regions of genomic imprinting have been identified on a
      small number of chromosomes through a search for the etiology of various
      disorders. Distinct phenotypes have been associated with both maternal and
      paternal uniparental disomy (UPD) for chromosome 14. This observation indicates
      that there are imprinted genes present on chromosome 14, although none have been
      identified to date. In order to focus the search for imprinted genes on
      chromosome 14, we analyzed cases of maternal and paternal UPD 14 and compared
      them with cases of chromosome 14 deletions. Cases of paternal UPD were compared
      with maternal deletions and maternal UPD compared with paternal deletions. The
      paternal UPD anomalies seen in maternal deletion cases allowed us to associate
      the following features and chromosomal regions: Hirsute forehead: del(14)(q12q13.
      3) and del(14)(q32); blepharophimosis: del(14)(q32); small thorax:
      del(14)(q11.2q13); and joint contractures: del(14)(q11.2q13) and del(14)(q31).
      Comparison of maternal UPD and paternal deletion cases revealed fleshy nasal tip
      to be most often associated with del(14)(q32), scoliosis with del(14) (q23q24.2),
      and del(14)(q32. 11qter) and small size at birth to be associated with
      del(14)(q11q13) and del(14)(q32). Our study, in conjunction with a prior study of
      UPD 14 and partial trisomy 14 cases, and what is known of imprinting in regions
      of mouse chromosomes homologous to human chromosome 14, leads us to conclude that
      14q23-q32 is likely an area where imprinted genes may reside.

PMID- 10951462
TI  - Malignant peripheral nerve sheath tumors in neurofibromatosis 1.
AB  - One of the most clinically aggressive cancers associated with neurofibromatosis 1
      (NF1) is the malignant peripheral nerve sheath tumor (MPNST). To determine the
      incidence and relative risk (RR) of MPNSTs in individuals with NF1, 1,475
      individuals with NF1 were included from a cohort of patients examined by a single
      experienced geneticist from 1977 to 1996. The end points were incidence of MPNST,
      relative risk of MPNST, and relative risk associated with specific NF1 physical
      findings. Thirty-four individuals were identified with MPNST (2%). The relative
      risk of MPNST was higher than expected with an RR value of 113 (95% confidence
      interval [CI] = 78-158). The average 10-year annual incidence of MPNST between
      the second and fifth decade of life was roughly the same with a range of 0.0013
      and 0.0068 MPNST per patient year. Most lesions occurred in the limbs (n = 18;
      53%), and those with limb lesions survived longer than those with nonlimb MPNSTs.
      Pain associated with a mass was the greatest risk factor associated with MPNST
      development (RR = 31.4; 95% CI = 13.2-75.1). Further biological and
      epidemiological studies are needed to determine other factors that influence the
      risk of MPNST development in individuals affected with NF1. Am. J. Med. Genet.
      93:388-392, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10951463
TI  - Tetrasomy 15q25-->qter: cytogenetic and molecular characterization of an
      analphoid supernumerary marker chromosome.
AB  - Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been
      previously described in seven patients, all of whom had a supernumerary marker
      chromosome (SMC) derived from distal 15q. These SMC contained no apparent
      centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC
      with neocentromeres. We present the oldest surviving patient with tetrasomy for
      distal 15q. The proposita was a 10-year-old girl with moderate to severe mental
      retardation, absent speech, hypotonia, minor facial anomalies, unusual digits,
      and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in
      metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal,
      indicating a de novo origin for the SMC. FISH with a whole chromosome paint for
      chromosome 15 showed that the SMC was derived entirely from chromosome 15.
      However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and
      PML were all negative. FISH with the FES probe at 15q26 showed hybridization to
      both ends of the SMC. The marker was interpreted as an analphoid inverted
      duplication of 15q25-->qter containing a presumed neocentromere. Previous
      molecular studies suggested either a mitotic or paternal meiotic origin for these
      distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic
      markers showed that the analphoid SMC(15) in the proposita originated from a
      maternal meiotic error. The origins and mechanisms involved in formation of these
      distal 15q SMC appear to be more diverse than for the proximal pseudodicentic
      SMC(15).

PMID- 10951464
TI  - Boy with celiac disease, malformations, and ring chromosome 13 with deletion
      13q32-->qter.
AB  - We describe a 2(1/2)-year-old boy with a ring chromosome 13 with distal deletion
      of 13q32-->qter and celiac disease.

PMID- 10951465
TI  - Genetic epidemiological study of keratoconus: evidence for major gene
      determination.
AB  - Keratoconus (KC) is a noninflammatory corneal thinning disorder and the major
      cause of cornea transplantation in the Western world. Genetic factors have been
      suggested in the cause of KC. We conducted a family study to investigate genetic
      contributions to the development of KC by evaluating familial aggregation and
      testing genetic models with segregation analysis. KC was diagnosed based on
      clinical criteria. Familial aggregation of KC was evaluated using both clinical
      status and three videokeratography indices generated by the Topographic Modeling
      System (TMS-1). The estimated KC prevalence in first-degree relatives was 3.34%
      (41/1,226, 95% CI: 3. 22-3.46%), which is 15 to 67 times higher than that in the
      general population (0.23-0.05%). For all three videokeratography indices, CK, IS,
      and KISA, KC propositi had significantly higher mean values than controls (all P
      < 0.0001). Clinically unaffected parents also had significantly higher values for
      these indices than controls (all P < 0.016). The correlation of KISA in sib and
      parent-offspring pairs (r = 0.30 and 0.22, respectively, both P < 0.0005) was
      significantly greater than that in marital pairs (r = 0.14), and the latter was
      not significantly different from zero. We performed segregation analysis on KISA
      in 95 families ascertained through KC propositi. Hypotheses of both sporadic and
      environmental models were rejected (P < 0.001); a major gene model was not
      rejected (P > 0.1). Additionally, the most parsimonious model was autosomal
      recessive. In conclusion, we observed strong evidence of familial aggregation in
      KC and its subclinical indices and this aggregation is likely due to a major gene
      effect.

PMID- 10951466
TI  - Determinants of parental decisions after the prenatal diagnosis of down syndrome:
      bringing in context.
AB  - This article develops the concept of decision context to refer to the
      combinations of factors that are important in understanding and predicting
      termination decisions after a prenatal diagnosis of trisomy 21. Four factors are
      examined: maternal age, gestational age, prior voluntary abortion, and existing
      children. The cases were studied at the Wayne State University's Reproductive
      Genetics Clinic. Qualitative comparative analysis, a technique specifically
      designed for examining the impact of combinations of factors, is used to isolate
      influential decision contexts. Odds and odds ratios are used to pinpoint outcome
      differences among different decision contexts. Four alternative decision contexts
      are especially conducive to choosing to terminate a pregnancy. Two of these
      involve women of any age and are formed from combinations of gestational age and
      existing children (existing children and low gestational age, and no children
      combined with late gestational age). Older women who have not had an abortion and
      who discover the trisomy 21 anomaly early are likely to choose termination.
      Younger women who have had an abortion are also likely to choose termination. Our
      data suggest there are added layers of complexity to patients' decisions that
      derive from combinations of conditions. An additional, strong implication is that
      qualitative comparative analysis may be particularly useful in understanding such
      complexity.

PMID- 10951467
TI  - Partially deleted SRY gene confined to testicular tissue in a 46,XX true
      hermaphrodite without SRY in leukocytic DNA.
AB  - True hermaphroditism is an uncommon form of intersexuality in which testicular
      and ovarian tissue develop in the same individual. Most true hermaphrodites are
      46,XX and lack SRY, the testis-determining gene. We describe results of molecular
      studies performed in a 46,XX true hermaphrodite SRY-negative in DNA from blood
      leukocytes but SRY-positive in DNA obtained from the testicular portion of the
      ovotestis. Surprisingly, the SRY identified in gonadal DNA carries a partial
      deletion at the 5' end of the gene. Our patient is the first case of a naturally
      occurring deletion within the SRY ORF (with a normal HMG box) and provides a new
      explanation for the abnormal gonadal development observed in 46,XX true
      hermaphrodites.

PMID- 10951469
TI  - Screening for fragile X syndrome in women of reproductive age.
AB  - We conducted a prospective intervention study of screening for fragile X syndrome
      in the general population. Antenatal and preconceptional screening were carried
      out in 9459 women aged between 19 and 44 with no known family history of fragile
      X syndrome. 80% were tested antenatally. 134 carriers were detected (a frequency
      of 1 in 70); 130 had a premutation (PM) and 4 had a full mutation (FM). Prenatal
      diagnosis was carried out in 108 concurrent or subsequent pregnancies among
      carriers involving 111 fetuses. Nine had an FM, a rate of 1 in 12; two of the
      affected embryos received the FM directly from the mother and in seven it was the
      result of expansion from a PM. In all cases with an FM the pregnancy was
      terminated. In PM carriers there was evidence of a selection against the mutated
      chromosome with a segregation ratio of 0.40. Owing to the high rate of premutated
      chromosomes in our population we conclude that screening for fragile X syndrome
      among women of reproductive age should be more widely available.

PMID- 10951468
TI  - Acampomelic campomelic dysplasia with SOX9 mutation.
AB  - Acampomelic campomelic dysplasia is a rare clinical variant of the more commonly
      encountered campomelic dysplasia (CMD1), characterized by absence of long bone
      curvature (acampomelia). We present a patient with acampomelic CMD1 with a de
      novo SOX9 missense mutation and report his clinical course to age one year,
      thereby contributing to genotype-phenotype correlation in CMD1. 2000.

PMID- 10951470
TI  - Prenatal diagnosis of fetal heart failure in twin reversed arterial perfusion
      syndrome.
AB  - Diagnosis of twin reversed arterial perfusion (TRAP) syndrome is a rare fetal
      anomaly that can be misdiagnosed on prenatal ultrasound. We confirmed the use of
      colour-flow Doppler for prenatal diagnosis of TRAP syndrome and used serial fetal
      echocardiography for non-invasive evaluation of the fetus. A patient with twin
      intrauterine pregnancy was referred to our centre with suspected intrauterine
      fetal demise following a 16 week ultrasound. Serial colour-flow Doppler
      ultrasonography demonstrated retrograde arterial flow in an acardiac twin.
      Following diagnosis of TRAP syndrome, serial fetal echocardiography was employed
      to follow the normal twin for signs of heart failure, including right atrial
      dilation, tricuspid regurgitation and pericardial effusion. When early signs of
      fetal heart failure were suspected a viable female infant was delivered at 32
      weeks' gestation. We suggest that serial fetal echocardiography represents a non
      invasive approach that can be used to follow fetal cardiac function of the normal
      twin in TRAP syndrome.

PMID- 10951471
TI  - Prenatal diagnosis of dominant dystrophic epidermolysis bullosa, by COL7A1
      molecular analysis.
AB  - We report the first direct molecular prenatal diagnosis, undertaken for the
      autosomal dominant form of dystrophic epidermolysis bullosa (DDEB). The proband
      had a moderately severe form of DDEB, with episodic blistering of skin and
      mucosal involvement. Diagnostic histopathological examination, using electron
      microscopy to evaluate skin from a fresh blister, demonstrated a zone of cleavage
      beneath the epidermal-dermal junction, thereby assigning the EB as dystrophic.
      DNA analysis of COL7A1, the gene encoding type VII collagen, identified a
      heterozygous transversion (G to A) in the triple helix domain (G2043R). For any
      subsequent pregnancy, the affected mother and the unaffected father of the
      proband requested prenatal prediction, which was thereafter carried out in DNA
      extracted from a chorionic villus sample obtained at 11 weeks of gestation.
      Restriction enzyme analysis of COL7A1 exons 73 and 74 amplified by PCR,
      demonstrated the presence of the G2043R mutation, and the pregnancy was
      subsequently terminated. Molecular analysis of DNA extracted from fetal tissues
      confirmed the prenatal prediction.

PMID- 10951472
TI  - Reference values of ductus venosus flow velocities and calculated waveform
      indices.
AB  - In recent years, investigations of the venous vascular system have become
      increasingly important in the assessment of fetal myocardial function. The aim of
      the present Doppler ultrasound study was to establish both new reference ranges
      for blood flow velocity during the different phases of the cardiac cycle (S, SD,
      D, a) and various calculated indices ((S-a)/S, (S-a)/V(mean), (S-a)D, S/D, a/S,
      S/a) for the ductus venosus. Pulsed-wave colour Doppler was used in this
      prospective cross-sectional study to examine 696 women with low-risk pregnancies
      during the period from 14 to 41 weeks' gestation. Reference curves were
      constructed for the individual measuring parameters based on a growth function
      from a four-parameter class of monotonic continuous functions according to the
      smallest square principle. A significant increase in blood flow velocity from 48
      cm/s to 65.8 cm/s was observed during ventricular systole (=S) from 14 to 41
      week's gestation. Similarly, increases in blood flow velocity were recorded
      during the endsystolic phase (=SD) (35.5 cm/s to 50.7 cm/s during early
      ventricular diastole (=D) (41.7 cm/s to 58 cm/s, p=0.0001) and atrial contraction
      (=a) (11.2 cm/s to 35 cm/s, p=0.0001), as well as for intensity-weighted mean
      velocity (30 cm/s to 48.3 cm/s). The venous indices were associated with
      significant decreases in the individual parameters with increasing gestational
      age: (S-a)/S from 0.77 to 0.47, (S-a)/V(mean) from 1.21 to 0.67, (S-a)/D from
      0.89 to 0.54, S/a from 4.5 to 1.99. A significant increase from 0.23 to 0.53 was
      observed only for the quotient a/S. There were no changes in the S/D quotient
      (from 1.15 to 1.13). Regarding intra-observer reliability, more favourable
      results were obtained for calculated indices than for measurements of absolute
      blood flow velocities. At constant measuring conditions, the reference ranges
      established by this study for blood flow velocities and calculated indices in the
      ductus venosus may serve as the basis for Doppler ultrasound follow-up in a
      normal patient population as well as for the diagnosis of fetal myocardial
      insufficiency of hypoxic and congestive origin.

PMID- 10951473
TI  - First trimester maternal serum AFP and total hCG in aneuploidies other than
      trisomy 21.
AB  - Total human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were
      measured in maternal serum at 10-14 weeks of gestation from 53 pregnancies
      affected by trisomy 18, 42 cases with trisomy 13, 46 with Turner's syndrome and
      13 with other sex aneuploides. The only significant association was the finding
      of reduced levels of total hCG in cases of trisomy 18 and 13. The association of
      increased levels of AFP in cases of trisomy 18 with ventral wall defects and the
      slight increase in AFP in cases of sex chromosomal anomalies other than Turner's
      syndrome was found. AFP and total hCG are not likely to replace the markers free
      beta-hCG and PAPP-A in first trimester screening for chromosomal anomalies.

PMID- 10951474
TI  - Differential effects of interleukin-3 on fetal and adult erythroid cells in
      culture: implications for the isolation of fetal cells from maternal blood.
AB  - Fetal clonogenic erythroid cells may be present in maternal blood and serve as a
      source of fetal DNA for prenatal genetic diagnosis. Proliferating nucleated red
      cells in cultures from first and second trimester fetal blood contain only fetal
      haemoglobin (HbF; F+A- cells), whereas nucleated red cells from adult blood
      contain also adult haemoglobin (HbA; F+A+ or F-A+ cells). Thus, fetal red cells
      can be identified and flow sorted. However, a few adult cells are also F+A-,
      which reduces the purity of fetal cell isolation. Culture media optimized for
      erythropoiesis contain interleukin-3 (IL3). We show here that IL3 strongly
      stimulates the growth of F+ cells (both F+A- and F+A+) in cultures from adult
      blood but has only a comparatively small effect on F+A- cells in cultures from
      fetal blood. This difference is maintained in the unified conditions of co
      cultures of adult and fetal cells, so that the purity of fetal cell sorts can be
      increased by omitting IL3 from the culture medium. We further show that IL3
      accelerates the exhaustion of the long-term division potential of adult cells,
      allowing fetal secondary colonies to be identified by their size following a two
      stage culture scheme. Thus, the choice to omit or include IL3 in the growth
      medium of maternal blood cultures should depend on whether fetal nucleated red
      cells are to be isolated by flow sorting after one week, or by picking secondary
      colonies after a later secondary culture stage.

PMID- 10951475
TI  - The influence of fetal sex in screening for Down syndrome in the second trimester
      using AFP and free beta-hCG.
AB  - In a study of 30 802 unaffected pregnancies and 90 cases of Down syndrome I have
      analysed second trimester maternal serum alpha-fetoprotein (AFP) and free beta
      human chorionic gonadotrophin (beta-hCG) and grouped the data by fetal sex. In
      pregnancies with an unaffected female fetus maternal serum AFP was significantly
      lower (3%) than in the presence of a male fetus, whilst free beta-hCG was
      significantly raised (7%) in the presence of a female fetus. These differences
      led to a significantly higher false positive rate in women carrying a female
      fetus (5.78% versus 4.64%). In pregnancies affected by Down syndrome the median
      AFP in the presence of a female fetus was not significantly different to that
      with a male fetus (0. 72 versus 0.73); similarly for free beta-hCG the difference
      (2.37 versus 2.48) was not statistically significant. Although the detection rate
      amongst male fetuses was slightly higher than in females (74% versus 66%), this
      was not statistically significant. Although fetal gender does appear to have a
      significant effect on maternal serum marker levels, leading to a higher false
      positive rate in females, in cases of Down syndrome there is no evidence that
      such marker differences are significant and consequently little evidence for any
      fetal gender bias in detection rates.

PMID- 10951476
TI  - Second-trimester prenatal screening for Down syndrome and the relationship of
      maternal serum biochemical markers to pregnancy complications with adverse
      outcome.
AB  - In a group of 26 524 control pregnancies and a group of 3728 pregnancies affected
      by one or more of the pregnancy complications of low birthweight, intra-uterine
      growth restriction (IUGR), preterm delivery and stillbirth, I have compared the
      relative risk of occurrence of these complications in pregnancies which had a
      raised maternal serum AFP (>2.0 MoM), raised maternal serum free beta-hCG (>2.0
      MoM), low AFP (<0.5 MoM), low free beta-hCG (<0.5 MoM), combined raised AFP and
      free beta-hCG (>2.0 MoM), and in those with an increased Down syndrome risk (1 in
      250 or greater). In the low birthweight group, only an increased AFP and
      decreased free beta-hCG showed significance with relative risks of 1.6 and 2.1.
      In the IUGR group, also only an increased AFP and decreased free beta-hCG showed
      significance with relative risks of 1.6 and 2.3. In the preterm delivery group,
      raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG
      showed significance with relative risks of 3.8, 1.8 and 6.2. In the stillbirth
      group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta
      hCG showed significance with relative risks of 4.5, 2,4 and 7.2. An isolated
      raised free beta-hCG or an increased Down syndrome risk were not associated with
      an increased relative risk for any of the pregnancy complications investigated.
      However, apart from the six to seven-fold increased risk when both AFP and free
      beta-hCG are above 2.0 MoM, suggesting increased risk of preterm delivery or
      impending fetal death, the clinical utility of such significant differences is
      probably poor.

PMID- 10951477
TI  - Fetal choroid plexus cysts: are we there yet?

PMID- 10951478
TI  - Prenatal diagnosis of a partial trisomy 19q.
AB  - Phenotypic anomalies due to a genetic imbalance of chromosome 19 have been
      reported in very rare postnatal cases. Here a case of partial trisomy 19
      diagnosed prenatally by ultrasonography and cytogenetic analysis is presented.
      Detailed evaluation by sonography showed major anomalies which could be
      correlated to the typical appearance of this chromosomal anomaly. Termination of
      pregnancy at 21 weeks of gestation was performed, and the prenatal diagnosis was
      confirmed postnatally by autopsy. The syndrome in this case was caused by a
      duplication of the long arm of chromosome 19 (46,XY, dup(19) (q13.1-->qter).

PMID- 10951479
TI  - Ultrasonographic prenatal diagnosis of microcephalic osteodysplastic primordial
      dwarfism types I/III.
AB  - Microcephalic osteodysplastic primordial dwarfism is a rare disease characterized
      by unique clinical appearance and specific radiographic findings, and distinctive
      brain abnormalities. We describe the prenatal diagnosis of two siblings with
      microcephalic osteodysplastic primordial dwarfism types I/III at 23 and 26 weeks
      of gestation, respectively. Early detection by sequential antenatal sonographic
      evaluation is important for counselling families known to be at risk of this rare
      disease.

PMID- 10951480
TI  - Pallister-Killian syndrome presenting through nuchal translucency screening for
      trisomy 21.
AB  - Pallister-Killian syndrome (tetrasomy 12p) is an uncommon aneuploidy, which may
      present in the prenatal period with an ultrasonographically detected fetal
      abnormality or following karyotyping for maternal age. We report a case that
      presented with increased nuchal translucency and hydrops at a first trimester
      screening scan for trisomy 21.

PMID- 10951481
TI  - The influence of fetal sex in screening for trisomy 21 by fetal nuchal
      translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of
      gestation.
AB  - In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21
      we have shown a significant difference in the median MoM of the markers: fetal
      nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a
      female fetus compared with a male fetus. For maternal serum free beta-hCG levels
      are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus
      has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal
      fetuses are 10% higher in the presence of a female fetus and 13% higher if the
      fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in
      both chromosomally normal and trisomy 21 female fetuses. The consequence of such
      changes when screening for trisomy 21 will be a reduction in the detection rate
      in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal
      sex, however, is probably not feasible, since ultrasound detection of fetal sex
      is only 70-90% accurate in the 10-14 week period.

PMID- 10951482
TI  - Maternal serum screening for trisomy 18: assessing different statistical models
      to optimize detection rates.
AB  - We have evaluated three alternative models for trisomy 18 screening using the
      maternal serum markers alpha-fetoprotein (AFP) and intact human chorionic
      gonadotrophin (hCG). Using data from 46 affected pregnancies and 48 150
      unaffected pregnancies, we calculated distribution parameters for AFP and hCG
      multiples of the median (MoMs) and the factor comprising AFP MoMxhCG MoM. The
      trisomy 18 risk at mid-trimester was then calculated using either bivariate
      analysis of AFP and hCG MoMs or univariate analysis of AFP MoMxhCG MoM. The
      observed detection rates and positive rates obtained using either published
      distribution parameters or those derived from the West Midlands population were
      compared for each model. Using fixed cut-offs for AFP and hCG of 0.66 and 0.40
      MoMs resulted in a detection rate of 28.3% for a 0.5% false positive rate (FPR).
      Using published parameters, the univariate analysis model had a slightly higher
      detection rate of 32.6% for a 0.5% FPR (cut-off 1:248) compared to the bivariate
      model which was 28.3% (cut-off 1:239). Locally derived distribution parameters
      significantly improved the detection rate for the bivariate model for FPRs
      between 0.4-1.3% but worsened it below 0.4%. For the univariate model there was
      little difference in detection whether local or published parameters were used.
      Thus, we have confirmed that trisomy 18 screening using two markers can be a
      worthwhile addition to Down screening.

PMID- 10951483
TI  - Second trimester levels of maternal serum inhibin A in pregnancies affected by
      fetal neural tube defects.
AB  - Inhibin A is effective as a second trimester maternal serum marker for Down
      syndrome screening. In the present study, inhibin A levels were measured in
      second trimester maternal serum samples from 28 pregnancies affected with open
      neural tube defects; 12 associated with open spina bifida and 16 associated with
      anencephaly. Each measurement was expressed as a multiple of the median (MoM) for
      control singleton pregnancies (n=1464) of the same completed week of gestation.
      Inhibin A levels were not significantly altered in cases of open neural tube
      defects; the median value was 0.96 MoM in cases of open spina bifida and 1.19 MoM
      in cases of anencephaly. Therefore, second trimester maternal serum inhibin A
      levels will not have an impact on prenatal detection of open neural tube defects.

PMID- 10951484
TI  - First trimester prenatal diagnosis of trisomy 21 in discordant twins using fetal
      nuchal translucency thickness and maternal serum free beta-hCG and PAPP-A.

PMID- 10951485
TI  - Prenatal screening for Down syndrome: pre-analytical precautions.

PMID- 10951486
TI  - Down syndrome fetal loss rate in early pregnancy.

PMID- 10951488
TI  - Current awareness in prenatal diagnosis.

PMID- 10951487
TI  - FISH in prenatal diagnosis.

PMID- 10951489
TI  - Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade
      dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers
      of cancer progression.
AB  - BACKGROUND: Prostate ducts and acini whose lumens are filled with malignant cells
      represent a well-recognized histological pattern recently termed intraductal
      carcinoma of the prostate (IDC-P). These tumors are often associated with rapid
      disease progression, and most recur after radical surgery. Controversy exists as
      to whether IDC-P should be recognized as a separate entity, an extension of high
      grade dysplasia (PIN) or invasive carcinoma as described by the Gleason grading
      system. This study investigates the use of molecular markers in defining the
      position of IDC-P in the evolutionary hierarchy of prostate cancer progression.
      METHODS: IDC-P, high-grade dysplasia, and invasive cancers from a cohort of 20
      selected radical prostatectomy specimens were screened for loss of heterozygosity
      (LOH), using 12 polymorphic microsatellite markers frequently lost in prostate
      cancer. RESULTS: LOH was absent in Gleason grade 3 cancer, infrequent in high
      grade dysplasia (9%) and Gleason grade 4 cancer (29%), but common in IDC-P (60%).
      In IDC-P, and to a lesser extent Gleason grade 4 cancers, multiple sites of
      allelic loss in individual cases were usual. CONCLUSIONS: Allelic instability
      provides further evidence that IDC-P is not a simple extension of dysplasia, nor
      does it represent invasion of Gleason grade 3 cancers into the ductal/acinar
      system. IDC-P and Gleason grade 4 cancer represent late but possibly separate
      events in prostate cancer evolution.

PMID- 10951490
TI  - Analysis of type T1 and T2 cytokines in patients with prostate cancer.
AB  - BACKGROUND: It has been proposed that a dysregulation in the balance between type
      T1 (IL-2, IFN-gamma) and type T2 (IL-4, IL-10) cytokines may be implicated in the
      development of cancer. METHODS: We determined the expression of IL-2, IL-4, IL
      10, and IFN-gamma in CD4 and CD8 lymphocytes by flow cytometry in 12 patients
      with prostate cancer and in 7 healthy subjects. In addition to the basal
      expression of these cytokines, their expression was also determined, following
      stimulation of lymphocytes with PMA (phorbol 12-mystirate 13 acetate) and
      ionomycin. RESULTS: The basal expression of cytokines was scarce, while following
      stimulation this increased markedly. On the other hand, there was a dysregulation
      in the balance between T1 and T2 lymphocytes in patients with prostate cancer. To
      this effect, in relation to healthy subjects, we observed an increase in IL-10
      expression and a decrease in IL-2 expression. CONCLUSIONS: The disequilibrium
      observed in the balance between type T1 and type T2 cytokines may be implicated
      in the evolution of neoplastic disease.

PMID- 10951491
TI  - Treatment of androgen-independent prostate cancer using antimicrotubule agents
      docetaxel and estramustine in combination: an experimental study.
AB  - BACKGROUND: Estramustine in combination with other chemotherapeutic agents has
      demonstrated synergy in hormone-refractory prostate cancer. Docetaxel has
      demonstrated antineoplastic activity in a variety of chemotherapeutic
      unresponsive tumors. We evaluated the effects of estramustine and docetaxel in
      preclinical models of prostate cancer. METHODS: Cell viability of PC-3 and MAT
      LyLu (MLL) cells were assessed 48 hr after drug treatment. For in vivo studies,
      each flank of five animals in six groups was injected with 1 x 10(6) MLL cells:
      control, estramustine, docetaxel (low- and high-dose), and low- and high-dose
      docetaxel with estramustine. Animals were treated on days 4 and 11, and
      sacrificed on day 14. RESULTS: The IC(50) value for docetaxel was 2 nM in the PC
      3 cells and 40 nM in the MLL cells. The addition of 100 nM of estramustine did
      not alter the IC(50) value for PC-3 cells. In the MLL cells, however, the IC(50)
      value was lowered to 15 nM. In vivo, low-dose docetaxel with estramustine
      demonstrated antineoplastic activity similar to that of high-dose docetaxel
      alone, suggesting additive activity between the drugs. CONCLUSIONS: These results
      demonstrate that when used in combination, docetaxel and estramustine can be more
      effective at lower dosages than when the individual drugs are used alone.

PMID- 10951492
TI  - Antibacterial activity of human prostasomes.
AB  - BACKGROUND: Prostasomes are prostate-derived organelles in semen exhibiting
      pluripotent properties. The present study deals with their possible antibacterial
      effects. METHODS: Antibacterial activity was assessed by growth inhibition of
      bacteria in an incubation medium containing prostasomes, after which the incubate
      was inoculated on cystine lactose electrolyte deficient agar (CLED) plates. In
      cases involving Bacillus megaterium, the effects were also documented
      ultrastructurally with scanning electron microscopy and atomic force microscopy.
      RESULTS: A dose-dependent growth inhibition was apparent, and a complete
      inhibition of growth was seen at a prostasome protein concentration of 30
      microg/ml with Bacillus megaterium. Ultrastructurally, increasingly irregular
      contours and a loosening of the smooth surface were observed, combined with a
      fragmentation of the bacteria. Among 9 other bacterial strains tested, a complete
      growth inhibition by prostasomes was attained in 3 strains, while the other 6
      were unaffected. CONCLUSIONS: Our data suggest that prostasomes, or prostasome
      derived proteins, are responsible for the antibacterial effects on Bacillus
      megaterium and some other bacterial strains. The results may serve as a basis of
      development of a new class of antibacterial drugs.

PMID- 10951494
TI  - Diagnostic frozen prostate sextant biopsies: an approach for preserving protein
      and RNA for additional studies.
AB  - BACKGROUND: Primary prostate cancer represents 29% of newly diagnosed visceral
      cancers in men. Despite this common occurrence, relatively little is known about
      the pathogenesis of this malignancy. High-grade prostatic intraepithelial
      neoplasia (HGPIN) is generally accepted as a precursor to invasive prostate
      carcinoma. There is a lack of adequate animal models, and the available cell
      culture lines are limited. Tissue from prostate needle core biopsies that have
      been frozen can provide adequate material for both diagnosis and research.
      METHODS: Transrectal sextant needle biopsies were snap-frozen, serially sectioned
      and alternately stained with hematoxylin-eosin or reacted with a basal cell
      specific antibody. Two pathologists examined all of the sections, which were
      scored for the presence or absence of carcinoma and HGPIN. Portions of the
      remaining tissue were used for studies of protein expression and gene expression.
      RESULTS: The incidence of carcinoma was 39%, comparable to the mean percent
      positive cases reported using conventional fixation and paraffin embedding. The
      incidence of HGPIN was 33%, higher than previously reported. CONCLUSIONS:
      Prostate carcinoma can be accurately diagnosed using frozen material. The
      observed high frequency of HGPIN is attributed to the instability of nuclear
      structure in the frozen material of the atypical nuclei, resulting in inflated
      grading of PIN lesions. Sufficient material remained in the frozen blocks for
      additional studies of protein and gene expression.

PMID- 10951493
TI  - Vitamin E and other antioxidants inhibit human prostate cancer cells through
      apoptosis.
AB  - BACKGROUND: Many human prostate cancer cells have escaped the apoptotic effects
      of natural regulators of cell growth such as transforming growth factor betal
      (TGF beta-1) and tumor necrosis factor (TNF). METHODS: Prostate cancer cell
      growth was investigated by treating with antioxidants. DU-145 (androgen
      unresponsive), LNCaP (androgen-responsive), and ALVA-101 (androgen moderately
      responsive) were grown in RPMI-1640 medium supplemented with bovine fetal calf
      serum and antibiotics, and were treated with various antioxidants for 1-7 days.
      Cell growth was then determined with the Cell Titer 96 AQ assay, and apoptosis
      was assessed by cell death detection ELISA, nuclear morphology, and TUNEL
      techniques. RESULTS: Cells treated with or without (+/-)-alpha-tocopherol
      (vitamin E) for 1-7 days at concentrations from 0.078-2.5 microg/ml modestly
      affected cell growth compared to other antioxidants tested. Tocopherol produced a
      significant (P < 0.01) inhibition of ALVA-101 and LNCaP (10-24% of control; 0.078
      2.5 microg/ml; at 6 days; n = 6). DU-145 cells were not growth-inhibited
      significantly. However, pyrrolidinedithiocarbamate (PDTC) produced a significant
      (P < 0.01, n = 6; 17-80% of control; 2.5-20 microg/ml; 1-7 days) inhibition of DU
      145 and ALVA-101 cells. A significant (P < 0.01) and maximum inhibition of LNCaP
      cells occurred at all concentration of PDTC (2. 5-20 microg/ml). A third
      compound, diethyldithiocarbamic acid (DETC), incubated for 1-7 days, produced a
      significant dose response suppression of cell growth of DU-145 and ALVA-101 cells
      (P < 0.01; 14-88% of control; 1.25-80 microg/ml; n = 6). LNCaP cells were
      inhibited by DETC (P < 0.01; 28% of control; 1.25-80 microg/ml; n = 6). All three
      antioxidants tested stimulated apoptosis in actively dividing ALVA-101, DU-145,
      and LNCaP cells (P < 0.01; n = 6), but confluent cells were affected less.
      Testosterone had additive inhibitory effects when combined with PDTC in ALVA-101
      cells; however, the other cell lines were not influenced. CONCLUSIONS: These
      results demonstrate that antioxidants modulate human prostate cancer cell
      proliferation by altering apoptosis in dividing cells, and this necrosis or
      apoptosis in confluent cells is not as effective.

PMID- 10951495
TI  - Changes in cell surface molecules associated with in vitro culture of prostatic
      stromal cells.
AB  - BACKGROUND: Prostate stromal cells can be readily cultured in vitro. Are these
      proliferating cells representative of stromal cells in situ? Since the expression
      of cell surface molecules, like the cluster of differentiation (CD) antigens, can
      be affected by changes in physiological conditions cultured stromal cells may
      differ from uncultured stromal cells in their complement of CD molecules.
      METHODS: Prostate stromal cells were prepared from tissue specimens and cultured.
      Flow cytometry was used to analyze the expression of 107 CD molecules in the
      resultant cells. Expression of the CD molecules by prostate cells in situ was
      done by immunohistochemistry. RESULTS: The expression of a number of cell surface
      molecules such as CD10, CD13, CD26, and CD44 is elevated in prostatic stromal
      cells cultured in vitro. These are markers of epithelial cells in tissue. Other
      molecules expressed by the cultured stromal cells include CD29, CD49a, CD49b,
      CD49d, CD49f, CD51/61, CD54, CD55, CD56, CD58, CD59, CD61, CD71, CD79b, CD81,
      CD82, CD90, CD95, CD107a, CD130, and CD147. Among these are stromal, epithelial,
      and nonstromal/nonepithelial markers as defined by tissue immunohistochemistry.
      CONCLUSION: Cultured stromal cells express a number of CD molecules normally
      found in other cell types of the prostate. Cells can express different CD
      molecules under different conditions.

PMID- 10951496
TI  - Antitumor activity of the polyamine analog N(1), N(11)-diethylnorspermine against
      human prostate carcinoma cells.
AB  - BACKGROUND: Recent studies indicate that N-terminally bis-ethylated-polyamine
      analogs have significant antitumor activity in several human solid-tumor models.
      In this study, the in vitro and in vivo antitumor potential of the polyamine
      analog N(1), N(11)-diethylnorspermine (DENSpm) in human prostate carcinoma cells
      was examined. METHODS: The antiproliferative and biochemical effects of DENSpm
      were tested in four human prostate cancer cell lines, i.e., PC-3, TSU-pr1, DU
      145, and JCA-1. The in vivo antitumor potential was explored in two groups of
      nude mice bearing small or more developed xenografts of the DU-145 cell line. The
      mice were treated with 40 mg/kg DENSpm, three times per day for two cycles of 6
      days, on days 1-6 and 8-13. RESULTS: In vitro studies showed that all four tested
      human prostate carcinoma cell lines were sensitive to DENSpm in micromolar
      concentrations. In tumor-bearing mice, DENSpm clearly prevented tumor growth in
      both size groups, which became significant after day 17. Treatment with DENSpm
      evoked intracellular accumulation of the analog and various regulatory responses,
      e.g., downregulation of the polyamine biosynthesis, the induction of the
      catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT), and the
      depletion or decrease of natural polyamines. The cellular sensitivity to growth
      inhibition by DENSpm only correlated with the degree of ODC inhibition and SSAT
      induction. CONCLUSIONS: DENSpm has sustained inhibitory effects on the growth of
      human prostate carcinoma cells in vitro as well in vivo. This polyamine analog
      may provide a new tool in the chemotherapy of prostate cancers with various
      phenotypes.

PMID- 10951497
TI  - Anatomic distribution of intraprostatic lymphatics: implications for the
      lymphatic spread of prostate cancer-a preliminary study.
AB  - BACKGROUND: Although prostate cancer metastasizes primarily into the lymphatic
      system, the anatomic distribution of intraprostatic lymphatics has not been
      elucidated. The aim of this study was to clarify the distribution of lymphatics
      in the human prostate by immunohistochemical techniques, using an anti
      desmoplakin antibody. METHODS: Whole-mount cryostatic sections were serially cut
      from the noncarcinomatous prostates of adult men with bladder carcinoma who
      underwent cystoprostatectomy. Each section was stained either with a monoclonal
      antibody specific for desmoplakin or with hematoxylin and eosin. RESULTS:
      Lymphatics were detected in all components of the prostate. In the glandular
      prostate, lymphatics were distributed evenly in the peripheral, transitional, and
      central zones. The lymphatic density was significantly high in the midbase region
      surrounding ejaculatory ducts. CONCLUSIONS: These results may indicate the
      importance of the midbase region as a route of lymphatic spread of prostate
      cancer.

PMID- 10951498
TI  - Low-dose staurosporine suppresses proliferation and induces neurites in human
      prostatic cancer TSU-Pr1 cells.
AB  - BACKGROUND: Despite the beneficial effects of androgen ablation therapy in
      patients with prostate carcinoma, advancing prostate cancer usually becomes
      hormone-refractory. We attempted to establish a new prostate cancer therapy by
      controlling the malignancy of tumor cells through the induction of
      differentiation in vitro. METHODS: We examined the ability of staurosporine to
      induce differentiation of human prostate cancer TSU-Pr1 cells into the cells with
      neuronal characteristics. RESULTS: At low concentrations, staurosporine
      remarkably suppressed proliferation of human prostate cancer TSU-Pr1 cells
      without increasing dead cell number. TSU-Pr1 cells treated with 10(-8) M
      staurosporine began to extend neurites within 1 day, and approximately 80% of
      cells were changed to a neuronal morphology at 3 days. The expression of mRNA of
      tau, a microtubule-associated protein that is one of the essential components of
      neurite outgrowth, time-dependently increased in the cells treated with 10(-8) M
      staurosporine. Similarly, the amount of acetylcholinesterase increased. Colony
      forming activity of TSU-Pr1 cells treated with 10(-8) M staurosporine for 7 days
      was 40% that of control cells. The invasive ability of TSU-Pr1 cells treated with
      staurosporine to penetrate through a reconstituted basement membrane of Matrigel
      was 20% that of untreated cells. CONCLUSIONS: These results suggest that
      staurosporine might induce differentiation of human prostate cancer TSU-Pr1 cells
      to cells with neuronal characteristics.

PMID- 10951499
TI  - FGF-10 is expressed at low levels in the human prostate.
AB  - BACKGROUND: Fibroblast growth factors (FGFs) are known to play an important role
      in the growth of normal prostatic epithelial cells. FGF-10 is a secreted growth
      factor that binds to FGF receptor-2 IIIb, which is expressed in prostatic
      epithelial cells and thus can potentially act as a growth factor for these cells.
      Prior work has indicated that FGF10 may play an important role in the development
      of the rat prostate, but its role in the adult human prostate is unclear.
      METHODS: Expression of FGF10 in human prostate tissue and primary cultures of
      prostatic epithelial and stromal cells was assessed by reverse-transcriptase PCR
      (RT-PCR) and Northern blotting. Growth response to FGF10 was assessed by the
      addition of recombinant FGF-10 to primary cultures of prostatic epithelial and
      stromal cells. RESULTS: FGF10 is expressed at levels detectable by RT-PCR and can
      act as a growth factor for prostatic epithelial cells, but is not active as a
      growth factor for stromal cells. However, FGF10 is expressed at extremely low
      levels relative to FGF7, which has a similar biological activity. CONCLUSIONS:
      While FGF10 may play a role in prostatic development, it is unlikely to play a
      major role in prostate growth in normal or hyperplastic adult human prostate, due
      to its extremely low expression compared to FGF7.

PMID- 10951500
TI  - Five meters of H(2)O: the pressure at the urinary bladder neck during human
      ejaculation.
AB  - BACKGROUND: There are no data in the literature on pressure changes in the
      prostatic urethra during ejaculation. In healthy men, it has always been
      postulated that there must be a pressure gradient in order to prevent retrograde
      ejaculation, but scientific proof for that is pending. METHODS: In five healthy
      male volunteers, the pressure profile in the prostatic urethra was registered
      during ejaculation, using a 10 French balloon catheter with 16 pressure channels.
      The channels were arranged in pairs at 5-mm intervals, beginning just below the
      balloon at the bladder neck and extending down to the external urethral
      sphincter. RESULTS: In the proximal part of the prostatic urethra, a pressure of
      up to 500 cm of H(2)O was measured in all subjects. Contrary to that, pressures
      did not exceed 400 cm of H(2)O distally to the verumontanum. CONCLUSIONS: A novel
      method to register the pressure profile in the lower urinary tract during
      ejaculation (ejaculomanometry) is presented. This study adds to the knowledge of
      the normal physiology of reproductive function and may be useful in the
      evaluation of male sexual and reproductive disorders.

PMID- 10951501
TI  - FACS for the isolation of individual cells from transgenic mice harboring a
      fluorescent protein reporter.
AB  - Flow cytometry is extensively used for the isolation of discreet populations of
      cells from complex pools. The advent of autofluorescent (AFP) reporters such as
      wild type Green Fluorescent Protein (wtGFP) (Chalfie et al., 1994) and its
      variants, including enhanced green fluorescent protein (EGFP) and enhanced yellow
      fluorescent protein (EYFP) (Cormack et al., 1996), as vital reporters opens up
      the possibility of sorting live reporter-expressing cells. Moreover the use of
      these reporters in transgenics (Okabe et al., 1997) or mice carrying homologously
      targeted loci (Godwin et al., 1998) should enable the direct isolation of
      reporter-expressing cells from any desired lineage. Here we have assessed this
      approach in transgenic mice. ES cell-mediated transgenesis was used for
      generating a line of mice that express an autofluorescent EYFP reporter in the
      heart and part of the neural tube at midgestation. Pools of fluorescent cells
      harboring and expressing the EYFP reporter were isolated from defined regions of
      embryos and their origin confirmed by assaying the expression of domain-defined
      marker genes. Such a tool should prove useful for gaining access to any given
      lineage that can be fluorescent protein reporter tagged.

PMID- 10951502
TI  - Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout
      mice.
AB  - While the targeted disruption of a gene is a powerful tool for investigating the
      physiological functions of that gene, disruption of a gene essential for
      embryogenesis leads to embryonic death. Rescue of the defect(s) causing embryonic
      death should promote survival, thus permitting further evaluation of the roles
      that the gene plays later in the developmental process. Disruption of the gene
      for mouse hepatocyte growth factor/scatter factor (HGF/SF) leads to middle-stage
      embryonic lethality because of a defect in placental development. Here we report
      that a single injection of HGF/SF at embryonic day 9.5 (E9.5) into the amniotic
      cavity of HGF/SF(-/-) embryos rescued the placental defect and resulted in the
      survival of the embryos until term. Histological analysis suggested that HGF/SF
      is also required at the late stage of development for tissue organogenesis. Thus,
      injection of a secreted factor can be a useful method to rescue the defects
      causing embryonic lethality.

PMID- 10951503
TI  - The maize CR4 receptor-like kinase mediates a growth factor-like differentiation
      response.
AB  - The maize crinkly4 (cr4) gene encodes a predicted receptor kinase that is
      required for the normal differentiation of leaf epidermis (Becraft et al., 1996).
      Here we confirm that the presumptive cytoplasmic domain is capable of
      autophosphorylation on serine and threonine residues. The cr4 transcript is most
      abundant in young developing tissues of the shoot but was not detected in the
      root. Phenotypic analysis of strong mutant alleles indicates that cr4 functions
      throughout shoot development to control the differentiation of internal as well
      as epidermal tissues. However, epidermal cells appear most sensitive to
      perturbations in CR4 signaling because epidermal defects are more pronounced than
      internal cell defects. Epidermal cells show irregularities in shape, cell wall
      thickness and structure, cuticle formation, and vesicle trafficking. Some plants
      show tumor-like proliferations of cells on the leaves. Thus CR4 regulates an
      array of developmental responses including cell proliferation, fate, pattern, and
      differentiation suggesting a function analogous to growth factor responses in
      animals.

PMID- 10951504
TI  - Fanconi anemia complementation group C is required for proliferation of murine
      primordial germ cells.
AB  - Fanconi anemia is a polygenic trait hypothesized to be a DNA damage repair
      disease. We show that all three Fanconi anemia loci that have been cloned are
      expressed in the embryonic gonad during the period of primordial germ cell
      proliferation. Mice mutant for the Fanconi anemia complementation group C locus
      (Fancc) have reduced germ cell numbers as early as embryonic day E12.5,
      suggesting the Fancc protein functions prior to meiosis in both sexes. Depletion
      in the mutant occurs at a time when all three loci would be expressed in a wild
      type gonad, implying a function in the early germline. Determination of the
      mitotic index of primordial germ cells by BrdU incorporation shows that germ
      cells in Fancc(-/-) mice proliferate significantly more slowly than littermate
      controls. This study demonstrates Fancc is required for mitotic proliferation of
      primordial germ cells.

PMID- 10951505
TI  - A subtractive gene expression screen suggests a role for vanin-1 in testis
      development in mice.
AB  - The molecular pathways leading from indifferent mammalian gonad to either testis
      or ovary are not well understood. A number of genes, including the Y-linked sex
      determining gene SRY, have been shown to play roles in sex determination or
      differentiation, but there are clearly many missing elements to be found. We used
      suppression-subtractive hybridization to construct normalized cDNA libraries
      enriched for male-specific or female-specific transcripts in mouse fetal gonads.
      We describe the strategy used to efficiently screen these libraries for candidate
      sex-determination and gonadogenesis genes. One gene arising from these screens is
      vanin-1, which encodes a protein implicated in the induction of cell migration
      into the thymus. We find that vanin-1 is expressed male-specifically in Sertoli
      cells of the developing testis and may be involved in inducing cell migration
      from the adjacent mesonephros, a process known to be critical for testis
      development. This screening approach is likely to be applicable to the isolation
      and study of genes involved in a variety of developmental systems.

PMID- 10951506
TI  - Erratum
AB  - "Mesenchymal-Epithelial Transition in the Developing Metanephric Kidney: Gene
      Expression Study by Differential Display," by Sergei Y. Plisov, Sergey V. Ivanov,
      Kiyoshi Yoshino, Lee F. Dove, Tatiana M. Plisova, Kathleen G. Higinbotham, Irina
      Karavanova, Michael Lerman, and Alan O. Perantoni The above article originally
      appeared in Volume 27, Number 1, the May 2000 issue, of genesis on pp. 22-31. The
      wrong affiliations were listed for two of the co-authors: Sergey V. Ivanov is
      affiliated with Intramural Research Support Program, SAIC-Frederick, Laboratory
      of Immunobiology, National Cancer Institute, Frederick Cancer Research and
      Development Center, Frederick, Maryland. Michael Lerman is affiliated with
      Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research
      and Development Center, Frederick, Maryland. On page 24, left column, under "In
      situ mRNA Hybridization" in the "Results" section, the sentence, "To verify the
      results of DD and to determine in which cells of the developing kidney the
      differentially displayed genes were expressed we applied mRNA hybridization
      (ISH)," should read: "To verify the results of DD and to determine in which cells
      of the developing kidney the differentially displayed genes were expressed we
      applied in situ mRNA hybridization (ISH)." On page 27, the legend for Figure 2,
      should read: "In situ RNA hybridization with thin sections of 19 dpc fetal
      kidney. Labeled antisense RNA was in vitro transcribed from cloned cDNA fragments
      obtained after differential display." On page 30, right column, under "In situ
      Hybridization" in the "Methods" section, the sentence, "To generate sense or
      antisense probes, 5 &mgr;g of plasmids with cloned cDNA fragments were linearized
      either with NcoI or SpeI (Promega) restriction enzymes and transcribed with T7 or
      SP6 RNA polymerase in the presence of alpha-35S-dCTP," should read: "To generate
      sense or antisense probes, 5 &mgr;g of plasmids with cloned cDNA fragments were
      linearized either with NcoI or SpeI (Promega) restriction enzymes and transcribed
      with T7 or SP6 RNA polymerase in the presence of alpha-35S-CTP." The authors
      regret these errors.

PMID- 10951508
TI  - No association between resting metabolic rate or respiratory exchange ratio and
      subsequent changes in body mass and fatness: 5-1/2 year follow-up of the Quebec
      family study.
AB  - OBJECTIVE: To investigate the relationships between resting metabolic rate (RMR)
      and respiratory exchange ratio (RER) and subsequent changes in body size and
      fatness. DESIGN: Prospective longitudinal observational study. PARTICIPANTS: A
      sample of 147 participants (76 males, 71 females) 18-68 y of age were followed
      for approximately 5-1/2 y. MEASURES: At baseline, post-absorptive RMR and RER
      were determined by indirect calorimetry and adjusted for the effects of age, body
      mass and subcutaneous fatness using regression procedures. Indicators of body
      size and fatness included body mass, waist circumference, and the sum of six
      skinfolds. Changes in these indicators (delta scores) were adjusted for age and
      length of the follow-up period using regression. RESULTS: Correlations between
      baseline RMR, RER and subsequent changes in the indicators of body fatness were
      uniformly low and not significant (range -0.05-0.16). Further, Cox proportional
      hazards regression analyses indicated that neither RMR nor RER were significant
      predictors of gains in body mass, waist circumference, or the sum of six
      skinfolds. CONCLUSIONS: There is no association between RMR or RER and changes in
      indicators of body size and fatness over 5(1/2) y of follow-up in this sample.
      European Journal of Clinical Nutrition (2000) 54, 610-614

PMID- 10951507
TI  - Relationships between transit time in man and in vitro fermentation of dietary
      fiber by fecal bacteria.
AB  - OBJECTIVE: To assess the effects of drug-induced changes in mean transit time
      (MTT) on the activity of human fecal flora in vitro. METHODS: The activity of
      fecal flora was estimated by the ability of a fecal inoculum to ferment a
      substrate (beet fiber) in vitro in a batch system for 24 h. The inoculum was
      collected from 8 healthy volunteers studied during three 3-week randomized
      periods, who received a controlled diet alone (control period) or the same diet
      with either cisapride or loperamide. Cisapride and loperamide were adjusted in
      order to halve and double MTT measured during the control period. At the end of
      each period, the percentage disappearance of the initial added substrate and the
      concentration and the profile of short-chain fatty acids (SCFAs), were
      determined. RESULTS: In the control period, the pH of the inoculum and SCFA
      concentration were inversely related to MTT (P=0.0001). Individual SCFA
      production was also significantly related to MTT (P<0.01). Cisapride-reduced
      transit time was associated with a significant rise in the concentrations of
      total SCFAs (P<0.05), propionic and butyric acids (P<0.05) and the percentage
      substrate disappearance (P<0.05). Inverse relations were observed during the
      loperamide period. Moreover, MTT was inversely related to the percentage
      substrate disappearance (P<0.001), SCFA production (P<0.001) and butyrate
      production (P<0.0005). CONCLUSION: Changes in MTT alter bacterial activity and
      modify the bacterial pathways affecting the proportion of individual SCFAs.
      European Journal of Clinical Nutrition (2000) 54, 603-609

PMID- 10951509
TI  - Low arginine plasma levels in patients after thoracoabdominal aortic surgery.
AB  - OBJECTIVE: Thoracoabdominal aortic surgery is a high-risk procedure and
      associated with a significant morbidity and mortality. Ischemia reperfusion of
      visceral organs and lower extremities is one of the most important determinants
      of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma
      levels are important in maintaining organ blood flow. Furthermore, arginine is
      important in wound healing and the immune system. Because of increased
      utilization of arginine, low arginine plasma levels could be expected after
      thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in
      these patients. DESIGN: Six patients with thoracoabdominal aortic aneurysm were
      included in this study. SETTING: University Hospital Vrije Universiteit,
      Department of Surgery, Amsterdam, The Netherlands. SUBJECTS: Six patients
      undergoing thoracoabdominal aortic surgery. INTERVENTION: Plasma levels of
      arginine were measured by high-performance liquid chromatography. RESULTS: Very
      low arginine plasma levels were seen on the first postoperative day. From day 1
      arginine slowly increased, but did not reach normal plasma levels on day 6.
      CONCLUSIONS: A significant decrease of arginine plasma levels was found and
      because of the fact that arginine has multiple functions, it may be important to
      keep these arginine plasma levels at normal or even higher levels in patients
      undergoing major vascular surgery. European Journal of Clinical Nutrition (2000)
      54, 615-617.

PMID- 10951510
TI  - Adipose tissue fatty acids and risk of myocardial infarction--a case-control
      study.
AB  - OBJECTIVES: To study the association between content in adipose tissue of very
      long-chain n-3 fatty acids, trans fatty acids, linoleic acid and alpha-linolenic
      acid and risk of a first myocardial infarction. DESIGN AND SUBJECTS: A case
      control design among 100 patients and 98 population controls both men and
      postmenopausal women, age 45-75 y. Adipose tissue fatty acids were determined by
      gas-liquid chromatography. Intake data were obtained through interview using a
      validated food frequency questionnaire. RESULTS: Dietary intake and adipose
      tissue content of the fatty acids studied correlated significantly. Adipose
      tissue contents of eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n
      3) and docosahexaenoic acid (22:6n-3) were significantly lower while those of
      trans fatty acids, linoleic and alpha-linolenic acid were significantly higher in
      patients than in controls. Age and sex adjusted odds ratios (OR) were
      significantly reduced with increasing quintiles of very long-chain n-3 fatty
      acids, thus the OR in the fifth compared to the first quintile was 0.23 (95% CI
      0.08-0.70). After further adjustment for waist-to-hip ratio, smoking, family
      history of CHD and content of trans fatty acids, the OR in the highest quintile
      was 0.17 (95% CI 0.04-0.76) and the P for trend 0. 016. Age and sex adjusted OR
      was increased in the fifth compared to the first quintile of trans fatty acids
      (OR 2.81, 95% CI 1.16-6.84), linoleic acid (OR 2.10, 95% CI 0.87-5.07) and alpha
      linolenic acid (OR 1.96, 95% CI 0.83-4.61), and P for trend was 0.002, 0.005 and
      0. 020, respectively. The trends remained significant after adjustment for waist
      to-hip ratio, smoking, and family history of coronary heart disease. Trans fatty
      acids, linoleic acid and alpha-linolenic acid in adipose tissue were strongly
      correlated, indicating a common source, most likely margarine. When each of these
      fatty acid species were adjusted for the two others the trends were no longer
      significant. CONCLUSION: Intake of very long-chain n-3 fatty acids as reflected
      in adipose tissue content is inversely associated with risk of myocardial
      infarction. Trans fatty acids, linoleic and alpha-linolenic acid were
      intercorrelated and associated with increased risk. It is suggested that the
      increased risk may be connected to trans fatty acids or to some other factor
      associated with margarine consumption. European Journal of Clinical Nutrition 54,
      618-625.

PMID- 10951512
TI  - Deficiencies of essential fatty acids, vitamin A and E and changes in plasma
      lipoproteins in patients with reduced fat absorption or intestinal failure.
AB  - OBJECTIVE: Deficiencies of essential fatty acids (EFA), vitamin A (retinol) and
      vitamin E (alpha- and gamma-tocopherol) were studied in non-HPN patients with
      different degrees of fat malabsorption (managing without home parenteral
      nutrition (HPN)), and in HPN-patients receiving HPN with and without parenteral
      lipids. DESIGN AND SUBJECTS: Phospholipid fatty acids (including EFA),
      cholesterol, retinol, alpha- and gamma-tocopherol in plasma and the intestinal
      absorption of fatty acids and energy (balance-studies) were measured in 40 non
      HPN patients, 44 HPN patients and 35 controls. Subgroups were non-HPN patients
      with fat:total energy absorption ratios >25% (A), between 15 and 25% (B), and
      <15% (C), and HPN patients receiving (D) and not receiving parenteral lipids (E).
      RESULTS: Intestinal absorption of the EFA linoleic acid was 8.2, 4.4, 3.8, 0.5
      and 0.5 g/day and corresponding plasma concentrations were 17.3%, 15.5%, 13.1%,
      12.1% and 8.9% in groups A-E, respectively (P<0.001). Deficiencies in EFA,
      defined as a Holman index >0.2 (20:3n-9/20:4n-6 ratio), were confined to 42% of
      the patients in group E. Plasma cholesterol was decreased in groups B-E. Plasma
      retinol was reduced (below the lower 2.5% confidence interval of controls) in 7%
      of non-HPN patients and in 20% of HPN patients. Plasma alpha-tocopherol was
      reduced in 64% of patients from groups B-E. Plasma gamma-tocopherol was decreased
      in 33% of the patients, except in HPN-patients receiving parenteral lipids.
      CONCLUSIONS: Plasma linoleic acid may decrease considerably (from 26% to 8-10%)
      as fat absorption decreases before secondary signs of essential fatty acid
      deficiencies occur (an increase in 20:3n-9 and the Holman index). In this study
      this was confined to patients on lipid-free HPN. Vitamin A deficiencies were
      mainly seen in HPN patients. Vitamin E deficiencies were common in both HPN and
      non-HPN patients, but administration of parenteral lipids normalized plasma gamma
      tocopherol. European Journal of Clinical Nutrition (2000) 54, 632-642.

PMID- 10951511
TI  - Vitamin D(3) and vitamin K(1) supplementation of Dutch postmenopausal women with
      normal and low bone mineral densities: effects on serum 25-hydroxyvitamin D and
      carboxylated osteocalcin.
AB  - OBJECTIVE: Improvement of vitamin D and K status of about 60 -y-old
      postmenopausal Dutch women. DESIGN: In a randomized study postmenopausal women
      with normal (T-score >-1; n=96) and low (T-score< or =-1; n=45) bone mineral
      density (BMD) of the lumbar spine, were supplemented with 350-400 IU vitamin
      D(3), 80 microg vitamins K(1) vitamins K(1)+D(3), or placebo for 1 y. Serum 25
      hydroxyvitamin D [25(OH)D] and percentage carboxylated osteocalcin (%carbOC) were
      measured at baseline and after 3, 6 and 12 months. RESULTS: Baseline %carbOC of
      the entire study population was positively correlated with BMD of the lumbar
      spine and femoral neck. Correspondingly, women with low BMD had lower %carbOC at
      baseline than women with normal BMD but this difference disappeared after 1 y of
      supplementation with vitamin K(1) ((mean+/-s.d.) 68+/-11% (95% CI, 64. 5-71.2%)
      vs 72+/-6% (95% CI, 70.1-72.9%), respectively). One year of supplementation with
      vitamin D(3) showed maximum increases in 25(OH)D of 33+/-29% (95% CI, 24.8-41.8%)
      and 68+/-58% (95% CI, 50.1-84.6%) in women with normal and low BMD, respectively.
      During winter, however, a 29% decline in maximum 25(OH)D levels was not prevented
      in women with low BMD. CONCLUSION: Daily supplementation of Dutch postmenopausal
      women with >400 IU vitamin D(3) is indicated to prevent a winter decline in
      25(OH)D and to control serum parathyroid hormone levels. Daily supplementation
      with 80 microg vitamin K(1) seems to be necessary to reach premenopausal %carbOC
      levels. A stimulatory effect of calcium and/or vitamin D on %carbOC cannot be
      excluded. European Journal of Clinical Nutrition (2000) 54, 626-631.

PMID- 10951513
TI  - The effect of leprosy-induced deformity on the nutritional status of index cases
      and their household members in rural South India: a socio-economic perspective.
AB  - OBJECTIVES: To determine whether the socioeconomic and nutritional status of
      cured leprosy patients with residual deformity, and their household members, was
      lower than that of cured leprosy patients without deformity. DESIGN: Cross
      sectional study. SUBJECTS: One hundred and fifty-five index cases with deformity,
      100 without deformity. Also 616 household members comprising 48% of the total
      members enumerated. MEASUREMENTS: Nutritional status was evaluated using
      anthropometry. Disease characteristics, socio-economic parameters and household
      information were recorded using a questionnaire. RESULTS: Index cases with
      deformity had lower community acceptance (P<0.001), and employment (P<0.001) than
      those cases without deformity. Households of index cases with deformity had a
      lower income (P<0.01) and a lower expenditure on food (P<0.05). The presence of
      deformity (odds ratio (OR): 2.1-3.2, P<0.01), unemployment (OR: 2.3-4.3, P<0.01)
      and female gender (OR: 2.4, P<0. 01) significantly increased the risk of index
      cases being undernourished, as judged by body mass index (BMI) alone, or BMI and
      mid-upper arm circumference. A low BMI (<18.5) in the index case significantly
      increased the odds of other adults (OR 2.2), adolescents (OR 2.9-3.8) and
      children (OR 2.2) in the household being undernourished. CONCLUSIONS: Cured
      leprosy index cases with physical deformity are more undernourished than index
      cases without deformity. This is associated with a reduced expenditure on food,
      possibly brought on by increased unemployment, and a loss of income.
      Undernutrition in the index case increases the risk of undernutrition in other
      members of the family. European Journal of Clinical Nutrition (2000) 54, 643-649.

PMID- 10951514
TI  - Iron stores and haemoglobin iron deficits in menstruating women. Calculations
      based on variations in iron requirements and bioavailability of dietary iron.
AB  - BACKGROUND: Iron stores and haemoglobin iron deficits in menstruating women can
      be calculated from body iron losses and absorption of dietary iron using recently
      developed methods. OBJECTIVE: To examine iron balance (iron status) expressed as
      body iron stores or haemoglobin iron deficits in menstruating women from amounts
      of iron lost (iron requirements) and amounts of dietary iron absorbed.
      Calculations are made both of stationary states and of the rate of changes in
      iron stores (iron status) when any of the two main factors determining iron
      balance are changed. DESIGN: The study is based on (1) previous and new equations
      describing relationships between iron absorption, iron requirements (losses),
      iron stores and/or haemoglobin deficits and (2) published data on iron
      requirements and their variation in menstruating adult women. RESULTS: Both iron
      stores and haemoglobin iron deficits are strongly related to iron requirements
      and absorption of dietary iron and follow the same equations during states of
      iron repletion and iron deficiency. When, for example, increasing or decreasing
      the bioavailability of the dietary iron, about 90% of the change in iron stores
      will occur within 1 y. CONCLUSIONS: There are strong relationships between iron
      requirements, bioavailability of dietary iron and amounts of stored iron. The
      observations that a reduction in iron stores and a calculated decrease of
      haemoglobin iron had the same increasing effect on iron absorption suggest that
      the control of iron absorption is mediated from a common cell, that may register
      both size of iron stores and hemoglobin iron deficit, eg the hepatocyte. European
      Journal of Clinical Nutrition (2000) 54, 650-657.

PMID- 10951515
TI  - Factors affecting reproducibility of dietary reports using food frequency
      questionnaires.
AB  - OBJECTIVE: To study the reproducibility of a food frequency questionnaire used to
      assess past dietary habits. DESIGN: Repeated retrospective assessment of dietary
      habits of a population sample. SETTING: Uppsala-Orebro Health Care Region of
      Sweden. SUBJECTS: One-hundred and four subjects participating as control subjects
      in a case-control study on thyroid cancer. INTERVENTIONS: Between spring 1993 and
      spring 1994 a case-control study was conducted in the study area, in order to
      investigate risk factors for thyroid cancer-diet among others. The study subjects
      reported their consumption of selected foods with reference 1-5 y before, as well
      as dietary changes that occurred from adolescence to adult age. One year later
      197 control persons were invited to provide a second report of the same food
      items. Of the invited subjects 104 agreed to participate. RESULTS: The median
      Spearman rank correlation coefficient between the first and second assessment was
      0.58 for food consumption and 0. 56 for nutrients intake. Correlation between the
      two assessments varied greatly between food items, ranging from -0.03 to 0.83.
      The correlation was positively related to the frequency and negatively related to
      the skewness of consumption. The recall of dietary changes from adolescence had a
      median correlation coefficient of 0. 38 (range 0.19-0.69). There were hints of a
      higher reproducibility of dietary reports among men and among highly educated
      subjects (more than 11 y of education), but these differences were statistically
      significant only for recall of adolescent diet. Reproducibility of nutrients
      intake was also significantly higher among men than among women, as well as among
      subjects older than 45 y. CONCLUSIONS: The reproducibility of dietary reports was
      satisfactory. Among factors affecting reproducibility, frequency and homogeneity
      of consumption in the source population are presumably the most important. Age,
      sex and education modify the inter-subject reproducibility of past diet. Based on
      reproducibility of a semi-quantitative index, the recall of adolescent diet
      probably has a low validity. European Journal of Clinical Nutrition (2000) 54,
      658-664.

PMID- 10951516
TI  - Evolution of meal patterns and food choices of Japanese-American females born in
      the United States.
AB  - OBJECTIVES: To examine trends in meal patterns and food choices across two
      generations of Japanese-American females born in the USA. DESIGN: Cross-sectional
      cohort study. SETTING: Gardena, a suburb of Los Angeles, California. SUBJECTS:
      One-hundred and seventy-six Japanese-American females, participating in a morning
      exercise class from December 1998 to January 1999. INTERVENTION: Eighty-eight
      Nisei (second generation) mothers and their Sansei (third generation) daughters
      completed a food frequency questionnaire, answering questions regarding meal
      patterns and consumption frequency of 51 food items. RESULTS: The Sansei ate
      fewer meals per day compared with the Nisei. Mean frequencies of takeout foods
      and eating out were higher in the Sansei vs the Nisei. Mean intake of meats and
      eggs were similar between the two groups. However, mean consumption of
      traditional Japanese complement foods including fish, vegetables and legumes was
      lower in the Sansei vs the Nisei. Intake of more 'Westernized' accessory foods,
      including salty snacks, regular soft drinks and alcoholic beverages, was higher
      in the Sansei vs the Nisei. CONCLUSION: Findings from this study indicate that
      meal patterns and food choices have changed in succeeding generations of Japanese
      American females from traditional fare to a diet containing many complement and
      accessory foods that are higher in fat, sugar, sodium and calories. Health
      professionals should be advised to consider the whole diet in making nutrition
      recommendations to this population as well as providing information to this group
      on the nutritional benefits of many traditional foods. European Journal of
      Clinical Nutrition (2000) 54, 665-670.

PMID- 10951518
TI  - A novel mutation, Ala315Ser, in FGFR2: a gene-environment interaction leading to
      craniosynostosis?
AB  - Mutations in the fibroblast growth factor receptor 1, 2 and 3 (FGFR1, -2 and -3)
      and TWIST genes have been identified in several syndromic forms of
      craniosynostosis. There remains, however, a significant number of patients with
      non-syndromic craniosynostosis in whom no genetic cause can be identified. We
      describe a novel heterozygous mutation of FGFR2 (943G --> T, encoding the amino
      acid substitution Ala315Ser) in a girl with non-syndromic unicoronal
      craniosynostosis. The mutation is also present in her mother and her maternal
      grandfather who have mild facial asymmetry but do not have craniosynostosis. None
      of these individuals has the Crouzonoid appearance typically associated with
      FGFR2 mutations. However, the obstetric history revealed that the proband was in
      persistent breech presentation in utero and was delivered by Caesarean section,
      at which time compression of the skull was apparent. We propose that this
      particular FGFR2 mutation only confers a predisposition to craniosynostosis and
      that an additional environmental insult (in this case foetal head constraint
      associated with breech position) is necessary for craniosynostosis to occur. To
      our knowledge, this is the first report of an interaction between a weakly
      pathogenic mutation and intrauterine constraint, leading to craniosynostosis.

PMID- 10951517
TI  - Physical map of a 1.5 mb region on 12p11.2 harbouring a synpolydactyly associated
      chromosomal breakpoint.
AB  - Synpolydactyly (SPD) is a rare malformation of the distal limbs known to be
      caused by mutations in HOXD13. We have previously described a complex form of SPD
      associated with synostoses in three members of a Belgian family, which co
      segregates with a t(12;22)(p11.2;q13.3) chromosomal translocation. The chromosome
      12 breakpoint of this translocation maps to 12p11.2 between markers D12S1034 and
      D12S1596. Here we show that a mutation in the HOXD13 gene is not responsible for
      the phenotype, and present a physical map of the region around the 12p11.2
      breakpoint. Starting from D12S1034 and D12S1596, we have established a contig
      approximately 1.5 Mb in length, containing 13 YAC clones, 16 BAC clones, and 11
      cosmid clones. FISH analysis shows that cosmid LL12NCO1-149H4 maps across the
      breakpoint, and Southern blot experiments using fragments of this cosmid as
      probes identify a rearranged BamHI fragment in the patients carrying the
      translocation. A search for expressed sequences within the contig have so far
      revealed one CpG island, seven anonymous ESTs and three previously characterised
      genes, DAD-R, KRAG and HT21, all of which were found not to be directly disrupted
      by the translocation. The gene represented by EST R72964 was found to be
      disrupted by the translocation. These findings lay the groundwork for further
      efforts to characterise a gene critical for normal distal limb development that
      is perturbed by this translocation.

PMID- 10951519
TI  - Spectrum of retGC1 mutations in Leber's congenital amaurosis.
AB  - Leber's congenital amaurosis (LCA) is the earliest and most severe form of all
      inherited retinal dystrophies responsible for congenital blindness. Genetic
      heterogeneity of LCA has been suspected since the report by Waardenburg of normal
      children born to affected parents. In 1995 we localised the first disease causing
      gene, LCA1, to chromosome 17p13 and confirmed the genetic heterogeneity. In 1996
      we ascribed LCA1 to mutations in the photoreceptor-specific guanylate cyclase
      gene (retGC1). Here, we report on the screening of the whole coding sequence of
      the retGC1 gene in 118 patients affected with LCA. We found 22 different
      mutations in 24 unrelated families originating from various countries of the
      world. It is worth noting that all retGC1 mutations consistently caused
      congenital cone-rod dystrophy in our series, confirming the previous genotype
      phenotype correlations we were able to establish. RetGC1 is an essential protein
      implicated in the phototransduction cascade, especially in the recovery of the
      dark state after the excitation process of photoreceptor cells by light
      stimulation. We postulate that the retGC1 mutations hinder the restoration of the
      basal level of cGMP of cone and rod photoreceptor cells, leading to a situation
      equivalent to consistent light exposure during photoreceptor development,
      explaining the severity of the visual disorder at birth.

PMID- 10951520
TI  - Stability and haplotype analysis of the FRAXE region.
AB  - FRAXE full mutations are rare and appear to be associated with mild mental
      retardation. As part of a screening survey of boys with learning difficulties to
      determine the frequency of full and premutations, we have collected data on the
      frequency of instability at FRAXE for about 4000 transmissions and the haplotype
      for over 7000 chromosomes. The distribution of FRAXE repeats was similar to other
      English populations but differed from two North American Caucasian series.
      Observed instability at FRAXE was rare but increased with increasing repeat
      number, and there were no expansions into the full mutation range, except in
      pedigrees ascertained through a full mutation. Haplotype analysis suggested
      division into five groups with each group having a characteristic distribution of
      FRAXE repeats. Fourteen of the 15 full mutations occurred on a single haplotype
      and this haplotype also had a significant excess of intermediate-sized alleles,
      suggesting that full mutations originate from large normal alleles. However, a
      related haplotype also had a significant excess of intermediates but we observed
      no full mutations on this haplotype, suggesting either loss or gain of stability
      determinants on it. We suggest that whilst triplet repeat size is a significant
      predisposing factor for expansion at FRAXE other genetic determinants are also
      likely to be important.

PMID- 10951521
TI  - Two p16 (CDKN2A) germline mutations in 30 Israeli melanoma families.
AB  - Germline mutations in the p16 (CDKN2A) tumour suppressor gene have been linked to
      inherited predisposition to malignant melanoma (MM). Variable frequencies of p16
      germline mutations were reported in different collections of melanoma families
      but it can be as high as 50%. Here we describe the results of p16 mutation
      screening in 30 melanoma kindreds in Israel. The entire coding region of the p16
      gene, including exons 1, 2 and 3, flanking exon/intron junctions, and a portion
      of the 3' untranslated (UTR) region of the gene were examined by single-stranded
      conformation polymorphism (SSCP) analysis and direct sequencing. Two p16 germline
      mutations were identified: G101W, which has been previously observed in a number
      of melanoma kindreds, and G122V, a novel missense mutation. Thus, the frequency
      of mutations identified in this collection of Israeli families was 7%. Functional
      analysis indicated that the novel G122V variant retained some capacity to
      interact with cyclin dependent kinases (CDKs) in vitro, yet it was significantly
      impaired in its ability to cause a G1 cell cycle arrest in human diploid
      fibroblasts. This partial loss of function is consistent with the predicted
      impact of G122V substitution on the 3-dimensional structure of the p16 protein.

PMID- 10951523
TI  - Linkage disequilibrium in isolated populations: Finland and a young sub
      population of Kuusamo.
AB  - Linkage disequilibrium (LD), non-random association of alleles at closely linked
      chromosomal loci, has been used as a tool in the identification of disease
      alleles, and this has led to an improved understanding of pathology in many
      monogenic Mendelian human diseases. We are currently moving from the mapping and
      identification of monogenic disease loci to attempts at identifying loci involved
      in predisposition to multifactorial diseases. In the selection of ascertainment
      strategies in the studies of these complex diseases, the extent of background LD
      in different populations is an important consideration. Here, we compare the
      extent of LD among the alleles of linked loci in a randomly ascertained sample of
      individuals from the Finnish population and a set of individuals ascertained from
      the region of Kuusamo, a small sub-population, founded some 13 generations ago,
      which has experienced very little subsequent immigration. Thirty-three
      microsatellite loci were genotyped in chromosomal regions on 13q, 19q, 21q, Xq,
      and Xp. The genetic diversity of these loci was determined separately in the
      general Finnish sample and in the Kuusamo sample. The X-chromosomal loci are
      characterised by higher levels of LD in the samples from Kuusamo than in the much
      larger (and older) general population of Finland, whereas in alleles of autosomal
      loci very little LD was seen in either of these two samples.

PMID- 10951522
TI  - Inverted duplications are recurrent rearrangements always associated with a
      distal deletion: description of a new case involving 2q.
AB  - We studied the case of a subject with an inverted duplication of 40 cM of 2q33
      q37 concurrent with a 10 cM deletion of the distal 2q, the latter not being
      detectable by cytogenetics. Microsatellite analysis demonstrated the absence of
      maternal alleles in the deleted region and a double dosage for one of the
      maternal alleles in the duplication region. We hypothesised that this type of
      rearrangement occurs at meiosis I, while the two homologues are synapsed for most
      of their length. The presence of inverted duplicons in the same chromosome arm
      would favour the partial refolding of one homologue into itself so leading to the
      intrachromatid synapsis and recombination of the inverted repeats. The arising
      recombinant chromosome is deleted for the region beyond the most distal repeat
      and with the chromatids joined together at the level of the region located
      between the two duplicons. At meiosis II, the two linked chromatids can join the
      opposite poles provided that a breakage between the two centromeres occurs
      leading to a duplicated/deleted chromosome and a simply deleted chromosome. This
      model can be extended to all the so-called inverted duplication cases and to part
      of the terminal deletions. In fact the finding that, in our invdup(2q), the
      entire 40 cM duplication region involves only one of the two maternal alleles,
      indeed indicates that the abnormal crossover occurs between sister chromatids.
      The phenotype associated with our 2q rearrangement led us to narrow the critical
      region for the Albright-like syndrome to 10 cM in the subterminal 2q region.

PMID- 10951525
TI  - Founder effect in spinal and bulbar muscular atrophy (SBMA) in Scandinavia.
AB  - We haplotyped 13 Finnish, 10 Swedish, 12 Danish and 2 Norwegian SBMA (spinal and
      bulbar muscular atrophy, Kennedy disease) families with a total of 45 patients
      and 7 carriers for 17 microsatellite markers spanning a 25.2 cM region around the
      androgen receptor gene on chromosome Xq11-q12 in search of a genetic founder
      effect. In addition, the haplotypes of 50 Finnish, 20 Danish and 22 Swedish
      control males were examined. All the Scandinavian SBMA families shared the same
      18 repeat allele for the intragenic GGC repeat, which was present in only 24% of
      the controls. Linkage disequilibrium was also seen for the closest microsatellite
      markers. In addition, extended haplotypes of the Finnish, Swedish and Danish SBMA
      families revealed country-specific common founder haplotypes, which over time
      became gradually shortened by recombinations. No common haplotype was found among
      the controls. The data suggest that the SBMA mutation was introduced into western
      Finland 20 generations ago. Haplotype analysis implies a common ancestor for the
      majority of Scandinavian SBMA patients.

PMID- 10951524
TI  - Linkage disequilibrium in inbred North African families allows fine genetic and
      physical mapping of triple A syndrome.
AB  - Triple A syndrome (Allgrove syndrome, MIM No. 231550) is a rare autosomal
      recessive disorder characterised by ACTH-resistant adrenal insufficiency,
      achalasia of the cardia, and alacrimia. The triple A gene has been previously
      mapped to chromosome 12q13 in a maximum interval of 6 cM between loci D12S1629
      and D12S312. Using linkage analysis in 12 triple A families, mostly originating
      from North Africa, we confirm that the disease locus maps to the 12q13 region
      (Zmax = 10.89 at theta = 0 for D12S1604) and suggest that triple A is a
      genetically homogeneous disorder. Recombination events as well as homozygosity
      for polymorphic markers enabled us to reduce the genetic interval to a 3.9 cM
      region. Moreover, total linkage disequilibrium was found at the D12S1604 locus
      between a rare allele and the mutant chromosomes in North African patients.
      Analysis of markers at five contiguous loci showed that most of the triple A
      chromosomes are derived from a single founder chromosome. As all markers are
      located in a 0 cM genetic interval and only allele 5 at the D12S1604 locus was
      conserved in mutant chromosomes, we speculate that the triple A mutation is due
      to an ancient Arabian founder effect that occurred before migration to North
      Africa. Since we also found linkage disequilibrium at D12S1604 in two patients
      from Southern Europe (France and Spain), the founder effect might well extend to
      other Mediterranean countries. Taking advantage of a YAC contig encompassing the
      triple A minimal physical region, the triple A gene was mapped to a 1.7 Mb DNA
      fragment accessible to gene cloning.

PMID- 10951526
TI  - Identification of an unbalanced cryptic translocation between the chromosomes 8
      and 13 in two sisters with mild mental retardation accompanied by mild dysmorphic
      features.
AB  - Recently, much attention has been given to subtelomeric chromosomal
      rearrangements as important aetiological factors leading to idiopathic mental
      retardation. However, detection of these aberrations is difficult, mostly due to
      technical limitations and lack of genotype-phenotype relationships. We report on
      a family with a history suggestive of segregation of a chromosomal anomaly. In
      two mildly mentally retarded sisters with a similar phenotype consisting of
      obesitas, skin atrophy of the lower limbs and mild facial dysmorphisms, a subtle
      unbalanced cryptic translocation (46,XX,der(13)t(8;13)(q24.3;q34)) was detected
      on routine cytogenetic investigation followed by additional FISH studies. The
      translocation originated from the mother.

PMID- 10951527
TI  - Mole maker phenotype: possible narrowing of the candidate region.
AB  - Recent data has suggested that familial recurrent hydatidiform mole is a rare
      autosomal recessive trait in women experiencing this gestational disease (MIM
      231090). Here we provide molecular data on an additional family confirming that
      recurrent familial hydatidiform moles are diploid, biparental and arise from
      independent conceptions. A narrowing of the gene interval on chromosome 19q13.3
      13.4 is suggested by haplotype analysis in two sisters.

PMID- 10951528
TI  - Exclusion of the Ellis-van Creveld region on chromosome 4p16 in some families
      with asphyxiating thoracic dystrophy and short-rib polydactyly syndromes.
AB  - Ellis-van Creveld syndrome (EVC) is a relatively rare, usually non-lethal,
      autosomal recessive skeletal dysplasia characterized by short stature,
      polydactyly, cardiac and renal anomalies. Linkage analysis has localized the
      disease gene to chromosome 4p16, with the markers at loci D4S827 and D4S3135
      defining the centromeric and telomeric limits of the linked interval,
      respectively. There has been long-term speculation that asphyxiating thoracic
      dystrophy (ATD) and the short-rib polydactyly syndromes (SRP) represent the
      severe end of the EVC disease spectrum. We performed linkage analysis using
      markers from the EVC region in seven families manifesting either ATD or SRP type
      III. In two of the families, one segregating ATD and one SRP kindred, linkage of
      the phenotype to the EVC region was excluded. In the other five families linkage
      of the phenotype to the EVC region could not be excluded, but the families were
      too small for linkage to the region to be established. The exclusion of the EVC
      region in ATD and SRP III families suggests that locus heterogeneity exists
      within the short-rib dysplasia (with and without polydactyly) group of disorders.

PMID- 10951529
TI  - Identification of genetic heterogeneity in Refsum's disease.
AB  - Refsum's disease (MIM 266500) is a recessive disorder characterised by defective
      peroxisomal alpha-oxidation of phytanic acid. A Refsum's disease gene, phytanoyl
      CoA hydroxylase (PAHX), has been localised to chromosome 10p13 between the
      markers D10S226-D10S223. This study investigated whether all cases of Refsum's
      disease were linked with chromosome 10p13. Eight genetically informative families
      comprising 92 individuals including 17 living patients with a Refsum's disease
      phenotype and initial plasma phytanic acid > 200 micromol/L were recruited.
      Linkage to the 10pter-10p11.2 region was investigated using a panel of eight
      dinucleotide repeat markers. Linkage analysis of this phenotypically identical
      cohort suggested that Refsum's disease was genetically heterogeneous (Zmax =
      5.28, alpha = 0.45). Two subgroups were identified. One group of four families
      with eight affected individuals had a maximum multipoint lod score for linkage of
      3.89 in the region D10S547 to D10S191, whilst in another three families with nine
      affected individuals linkage to this region was definitely excluded. Our results
      show that Refsum's disease is genetically heterogeneous, with up to 55% of cases
      not being linked to the PAHX gene locus at D10S547 to D10S223. This suggests that
      Refsum's disease, in common with other peroxisomal 'diseases', may be more
      accurately described as a heterogeneous syndrome.

PMID- 10951530
TI  - Overweight and obesity among Alaskan Eskimos of the Bering Straits Region: the
      Alaska Siberia project.
AB  - OBJECTIVE: To document the height, weight, BMI and prevalence of obesity for
      Eskimo residents of four villages of the Bering Straits Region of Alaska. DESIGN
      AND SUBJECTS: 454 Non-pregnant residents over 24 y of age, with at least one
      Eskimo grandparent participated in one cross sectional survey within each
      village. MEASUREMENTS: Height, weight, calculation of BMI (kg/m2), proportion of
      'overweight' (BMI 25-29.9), and proportion of 'obese' (BMI>/=30). RESULTS: For
      women and men, respectively, mean heights were 153.4 and 165.2 cm; weights were
      64.2 and 71.6 kg; and BMI were 27.2 and 26.2 kg/m2 after age standardization. For
      women, 27.9% were overweight, and 32.8% were obese compared with 36.2% and 15.6%,
      respectively, for men. Alaskan Eskimo participants of the Alaska Siberia Project
      had a significantly lower proportion of total overweight (BMI>/=25, 54.9% for
      women, and 32.0% for men) compared with the three sites of the Strong Heart
      Study, which ranged from 65.9 to 80.2% for women and 53.6 to 66.7% for men.
      Compared with American men of all races, the proportion of overweight and obese
      participants was similar for Eskimo men. The proportion of obese was
      significantly higher for Eskimo women compared with American women of all races,
      but the proportion of overweight was similar. CONCLUSION: Although the prevalence
      of obesity among the Alaskan Eskimos is lower than for American Indians, the high
      proportion of overweight observed in this study is of concern for Alaskan Eskimo
      adults, especially for women.

PMID- 10951531
TI  - Common apolipoprotein A-IV variants are associated with differences in body mass
      index levels and percentage body fat.
AB  - OBJECTIVE: To determine the relationship between two common apoA-IV variants
      (Thr347-->Ser; Gln360-->His), and body mass index (BMI) and percentage body fat.
      DESIGN: Cross-sectional study. SUBJECTS: Eight-hundred and forty-eight subjects
      screened for participation in ongoing clinical studies. MEASUREMENTS: ApoA-IV
      genotype, body mass index, waist-to-hip ratio and percentage body fat by
      bioelectric impedance. RESULTS: Participants had an average age of 41+/-12 y and
      an average BMI of 28.2+/-5.5 kg/m2. Individuals homozygous for the Ser347 allele
      had higher BMI (32.3+/-6.6 vs 28.6+/-5.3 kg/m2; P<0.01) and percentage body fat
      (36.9+/-7.8 vs 31.0+/-9.6%; P<0.05) compared with individuals homozygous for
      Thr347. In contrast, the presence of at least one copy of the His360 allele was
      associated with lower BMI (27.2+/-5.0 vs 28.4+/-5.6 kg/m2; P<0.05) and percentage
      body fat (28.6+/-8.2 vs 30.7+/-9.1%; P<0.05). The genotype effects persisted
      after normalization of the data for the potential confounding effects of gender,
      age and race. When grouped by BMI percentile, the frequency of the Ser347/Ser347
      genotype increased while the frequency of the His360 allele decreased with
      increasing BMI. CONCLUSIONS: These data suggest a role for apoA-IV in fat storage
      or mobilization and that genetic variations in the apoA-IV gene may play a role
      in the development of obesity.

PMID- 10951532
TI  - Obesity and left ventricular diastolic function: noninvasive study in
      normotensives and newly diagnosed never-treated hypertensives.
AB  - OBJECTIVE: To evaluate the influence of obesity, per se or associated with
      hypertension, on left ventricular (LV) diastolic function. PATIENTS: Thirty-two
      obese newly-diagnosed never-treated hypertensives; 32 obese normotensives matched
      for age, sex and BMI with hypertensives; 32 lean newly diagnosed never-treated
      hypertensives and 32 lean normotensives, matched for age, sex and 24 h blood
      pressure (BP) with the obese subjects. METHODS: Twenty-four-hour ambulatory blood
      pressure monitoring and digitized M-mode LV echocardiograms. PARAMETERS
      EVALUATED: Twenty-four-hour, day-time and night-time BP and heart rate,
      percentage nocturnal BP fall; LV end-diastolic diameter index, septal and
      posterior wall thickness, LV mass index, peak shortening and lengthening rate of
      LV diameter, peak thinning rate of LV posterior wall. RESULTS: A main effect was
      found for obesity on LV diameter and LV mass and for hypertension on LV mass; LV
      systolic function was normal in all the subjects and similar among the four
      groups; LV diastolic function was significantly reduced in both obese groups with
      respect to lean ones. This difference persisted after correction of diastolic
      parameters for 24 h BP and heart rate, LV diameter and LV mass index and
      disappeared only after correction for body mass index. This latter was inversely
      related with diastolic parameters only in the obese groups. CONCLUSIONS: Obesity
      is associated with a preclinical impairment of LV diastolic function in both
      normotensives and hypertensives; the diastolic impairment is independent of
      haemodynamic factors, such as 24 h BP and heart rate, and bears no relation to LV
      geometry in normotensives and only little relation in hypertensives, having
      therefore to be ascribed to obesity itself.

PMID- 10951533
TI  - Overweight and obesity in preschool children from developing countries.
AB  - OBJECTIVES: To estimate levels and trends in overweight and obesity in preschool
      children from developing countries; to study how overweight varies by the
      educational level of the mother, by urban or rural residence, and by gender; to
      investigate how these relationships are related to the gross national product
      (GNP). DESIGN: 71 national nutrition surveys since 1986 from 50 countries were
      used. SUBJECTS: 150,482 children 12 to 60 months from the most recent survey from
      each country were the primary sample. MEASUREMENTS: Overweight and obesity were
      defined as weight-for-height (>1 or >2 s.d., respectively) of the WHO/NCHS
      reference curves. Stunting was <-2 s.d. of the same reference. Urban was as
      defined in each of the surveys and higher education was defined as at least one
      year of secondary schooling or higher. RESULTS: 32 of 50 countries had a
      prevalence of obesity below 2.3%, the value in the reference population. The
      prevalences of overweight and obesity were lowest in Asia and in Sub-Saharan
      Africa. In 17 countries with serial data, no consistent regional trends could be
      detected. Overweight was more common in urban areas, in children of mothers with
      higher education, and in girls; these relationships did not differ by GNP but GNP
      was related negatively to stunting and positively to overweight. CONCLUSIONS:
      Obesity does not appear to be a public health problem among preschool children in
      Asia and Sub-Saharan Africa. In a number of countries in Latin America and the
      Caribbean, the Middle East and North Africa, and the region of Central Eastern
      Europe/Commonwealth of Independent States, levels are as high as in the United
      States.

PMID- 10951535
TI  - Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the relation between plasma leptin concentrations and
      metabolic control in human diabetes mellitus. DESIGN AND SUBJECTS: Cross
      sectional study consisting of 156 patients with diabetes mellitus type 1 (n=42),
      type 2 (n=114), and non-diabetic subjects (n=74). RESULTS: Plasma leptin
      concentrations were lower (P<0.05) in type 1 (8.3+/-1.7 ng/ml) and type 2
      diabetic (14.9+/-1.8 ng/ml) than in non-diabetic humans (18.3+/-1.9 ng/ml). Only
      female type 1 and type 2 diabetic subjects also had decreased leptin/BMI ratios
      (P<0.05 vs non-diabetic females). The log rank test identified age-adjusted
      correlation of plasma leptin concentration with sex (P<0.0004) and body mass
      index (P<0.0218), but not with glycosylated haemoglobin A1c (P>0.5) in all
      groups. Plasma leptin was correlated with age (P<0.0058) and serum triglycerides
      (P<0.0199) in type 1 diabetic patients, and with serum cholesterol (P<0.0059) and
      LDL (P<0.0013) in type 2 diabetic patients. CONCLUSIONS: Defective leptin
      production and/or secretion might be present independently of metabolic control
      in female patients with type 1 or type 2 diabetes mellitus.

PMID- 10951534
TI  - Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by
      fasting and growth hormone treatment in obese humans.
AB  - OBJECTIVE: To investigate whether the expression of uncoupling proteins (UCP2 and
      UCP3) was affected by a very low calorie diet (VLCD) and growth hormone (GH)
      treatment for 4 weeks. DESIGN: A randomized, placebo-controlled intervention
      study of VLCD with or without concomitant GH-treatment. SUBJECTS: Seventeen obese
      women (body mass index, BMI=42.1+/-1.4 kg/m2 (range 31.8-54.5 kg/m2)) treated
      with VLCD for 4 weeks and randomized to concomitant placebo treatment (n=9) or GH
      treatment (n=8). MEASUREMENTS: Fat mass and lean body mass were measured by dual
      energy X-ray absorptiometry. Energy expenditure (EE) was measured by indirect
      calorimetry. UCP2 and UCP3 mRNA were measured in adipose tissue and skeletal
      muscle biopsies before VLCD and after VLCD+/-GH-treatment by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: VLCD treatment
      resulted in a mean weight loss of 5.23 kg+/-0.8 (P<0.01), a 4.1% decrease in EE
      (P<0.05) and a 24% decrease in UCP3 mRNA in adipose tissue (P<0.03), whereas
      adipose tissue UCP2 mRNA and skeletal muscle UCP2 and UCP3 mRNA levels were
      unchanged. GH-treatment had no effects on EE, changes in body weight or UCP mRNA
      level. In multiple regression analysis the change in EE caused by VLCD was
      significantly correlated with changes in adipose tissue UCP2 mRNA (r=0.66,
      P<0.02) and a tendency towards a significant association with the change in
      adipose tissue UCP3 mRNA (r=0.45, P=0.09), but not with change in body weight,
      skeletal muscle UCP2 or UCP3 mRNA levels. CONCLUSION: VLCD for 4 weeks decreased
      UCP3 mRNA expression in human adipose tissue, whereas GH-treatment had no effect
      on UCP expression. Multiple regression analysis demonstrated that changes in
      adipose tissue UCP2 and probably UCP3 mRNA were correlated with the change in EE.
      These findings indicate that UCPs in adipose tissue in very obese individuals
      might play a role for the reduction in EE observed during energy restriction.

PMID- 10951536
TI  - Estimation of body fat from anthropometry and bioelectrical impedance in Native
      American children.
AB  - OBJECTIVE: Obesity, as measured by body mass index, is highly prevalent in Native
      American children, yet there are no valid equations to estimate total body
      fatness for this population. This study was designed to develop equations to
      estimate percentage body fat from anthropometry and bioelectrical impedance as a
      critical part of Pathways, a multi-site study of primary prevention of obesity in
      Native American children. DESIGN: Percentage fat was estimated from deuterium
      oxide dilution in 98 Native American children (Pima/Maricopa, Tohono O'odham and
      White Mountain Apache tribes) between 8 and 11 y of age. The mean fat content
      (38.4%+/-8. 1%) was calculated assuming the water content of the fat-free body
      was 76%. Initial independent variables were height, weight, waist circumference,
      six skinfolds and whole-body resistance and reactance from bioelectrical
      impedance (BIA). RESULTS: Using all-possible-subsets regressions with the Mallows
      C (p) criterion, and with age and sex included in each regression model, waist
      circumference, calf and biceps skinfolds contributed least to the multiple
      regression analysis. The combination of weight, two skinfolds (any two out of the
      four best: triceps, suprailiac, subscapular and abdomen) and bioelectrical
      impedance variables provided excellent predictability. Equations without BIA
      variables yielded r2 almost as high as those with BIA variables. The recommended
      equation predicts percentage fat with a root mean square error=3.2% fat and an
      adjusted r2=0.840. CONCLUSION: The combination of anthropometry and BIA variables
      can be used to estimate total body fat in field studies of Native American
      children. The derived equation yields considerably higher percentage fat values
      than other skinfold equations in children.

PMID- 10951537
TI  - Increased adiposity in animals due to a human virus.
AB  - BACKGROUND: Four animal models of virus-induced obesity including adiposity
      induced by an avian adenovirus have been described previously. This is the first
      report of adiposity induced in animals by a human virus. OBJECTIVE: We
      investigated the adiposity promoting effect of a human adenovirus (Ad-36) in two
      different animal models. DESIGN: Due to the novel nature of the findings we
      replicated the experiments using a chicken model three times and a mammal model
      once. In four separate experiments, chickens and mice were inoculated with human
      adenovirus Ad-36. Weight matched groups inoculated with tissue culture media were
      used as non-infected controls in each experiment. Ad-36 inoculated and uninfected
      control groups were housed in separate rooms under biosafety level 2 or better
      containment. The first experiment included an additional weight matched group of
      chickens that was inoculated with CELO (chick embryo lethal orphan virus), an
      avian adenovirus. Food intakes and body weights were measured weekly. At the time
      of sacrifice blood was drawn and visceral fat was carefully separated and
      weighed. Total body fat was determined by chemical extraction of carcass fat.
      RESULTS: Animals inoculated with Ad-36 developed a syndrome of increased adipose
      tissue and paradoxically low levels of serum cholesterol and triglycerides. This
      syndrome was not seen in chickens inoculated with CELO virus. Sections of the
      brain and hypothalamus of Ad-36 inoculated animals did not show any overt
      histopathological changes. Ad-36 DNA could be detected in adipose tissue, but not
      skeletal muscles of randomly selected animals for as long as 16 weeks after Ad-36
      inoculation. CONCLUSIONS: Data from these animal models suggest that the role of
      viral disease in the etiology of human obesity must be considered.

PMID- 10951538
TI  - Retinoid X receptor agonists have anti-obesity effects and improve insulin
      sensitivity in Zucker fa/fa rats.
AB  - OBJECTIVE: To investigate whether retinoid X receptor agonists act as insulin
      sensitizers and compare their effects with that of thiazolidinedione BRL 49653 in
      obese Zucker rats. DESIGN: In two independent studies, obese Zucker rats were
      dosed orally once daily for 14 days with one of the following treatments: LG
      100268 (20 mg/kg), LG 100324 (20 mg/kg), BRL 49653 (3 mg/kg) or vehicle.
      MEASUREMENTS: Daily food intake and body weight gain, blood glucose, plasma and
      pancreatic insulin, whole body glucose disposal (by euglycaemic-hyperinsulinaemic
      clamp) and tissue glucose utilization. RESULTS: The retinoid X receptor agonists
      (rexinoids) LG 100268 and LG 100324 caused a reduction in the food intake of
      obese Zucker rats relative to controls and to rats receiving BRL 49653. The two
      rexinoids also produced a marked decrease in the body weight gain, whereas the
      growth rate of rats treated with BRL 49653 tended to increase. Both rexinoids and
      BRL 49653 reduced the plasma insulin concentration of fed rats. LG 100268 and LG
      100324 also significantly lowered blood glucose concentrations after 1 week of
      treatment. The 5 h fasted plasma insulin concentration was significantly lower in
      the rexinoid-treated groups and the terminal insulin level (at the end of the
      clamp) tended to be lower in all treated groups compared with animals given the
      dosing vehicle. However, pancreatic insulin content was not affected by any of
      the treatments. Under euglycaemic-hyperinsulinaemic clamp conditions, there were
      no significant differences in the rate of hepatic glucose output and whole body
      glucose disposal, except that, in experiment 1, BRL 49653 caused significant
      increase in the glucose infusion rate and muscle glucose utilization. In
      experiment 2, a similar glucose infusion rate to the controls was achieved in all
      treatment groups but the steady-state insulin concentration in the treated
      animals was only about 50% of that in the control animals, despite the fact that
      all rats received a similar insulin infusion concentration. This suggests that
      both the rexinoids and BRL 49653 increased insulin clearance. CONCLUSIONS:
      Chronic administration of retinoid X receptor agonists LG 100268 and LG 100324 to
      Zucker fa/fa rats reduces food intake and body weight gain, lowers plasma insulin
      concentrations while maintaining normoglycaemia, indicating an improvement of
      insulin sensitivity.

PMID- 10951539
TI  - Waist circumference and abdominal sagittal diameter as surrogates of body fat
      distribution in the elderly: their relation with cardiovascular risk factors.
AB  - OBJECTIVE: To evaluate the relationship between supine sagittal abdominal
      diameter (SAD) and other indicators of body fat distribution with cardiovascular
      (CVD) risk factors in the elderly. SUBJECTS: One-hundred and forty-six women aged
      from 67 to 78 y with a body mass index (BMI) ranging from 18.7 to 50.6 kg/m2 and
      83 men aged between 67 and 78 y with BMI ranging from 19.8 to 37.1 kg/m2.
      MEASUREMENT: Body fat distribution was assessed using anthropometric indicators:
      waist circumference, SAD, waist-to-hip ratio (WHR), waist-to-height ratio and SAD
      to-thigh ratio. RESULTS: In women, there was a negative correlation between HDL
      cholesterol and body weight, BMI, waist, SAD, WHR, waist-to-height ratio and SAD
      to-thigh ratio. A significant association was found between triglycerides, basal
      glucose, 2 h glucose during oral glucose tolerance test (OGTT), systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and anthropometric variables. In
      men a negative correlation was found between HDL-cholesterol and all the
      anthropometric variables. A significant association was found between
      triglycerides, DBP and body weight, BMI, waist, SAD and waist-to-height ratio. In
      women, after adjusting for age and BMI, a significant correlation was observed
      between waist and HDL-cholesterol, triglycerides and basal glucose. This was also
      seen with SAD and SAD-to-thigh ratio and triglycerides, basal and 2 h glucose. In
      men, after adjusting for age and BMI a significant correlation was found between
      SAD and HDL-cholesterol and triglycerides. When adjustments were made for age and
      waist, the correlations between BMI and metabolic variables as well between BMI
      and SBP and DBP were no longer significant. CONCLUSIONS: Our study shows that
      indicators of body fat distribution are associated with CVD risk factors in the
      elderly independently of BMI. Our data also show that waist and SAD are the
      anthropometric indicators of fat distribution which are most closely related to
      CVD risk factors in old age.

PMID- 10951540
TI  - The paradox of low body mass index and high body fat percentage among Chinese,
      Malays and Indians in Singapore.
AB  - OBJECTIVE: To study the relationship between body fat percentage and body mass
      index (BMI) in three different ethnic groups in Singapore (Chinese, Malays and
      Indians) in order to evaluate the validity of the BMI cut-off points for obesity.
      DESIGN: Cross-sectional study. SUBJECTS: Two-hundred and ninety-one subjects,
      purposively selected to ensure adequate representation of range of age and BMI of
      the general adult population, with almost equal numbers from each ethnic and
      gender group. MEASUREMENTS: Body weight, body height, sitting height, wrist and
      femoral widths, skinfold thicknesses, total body water by deuterium oxide
      dilution, densitometry with Bodpod(R) and bone mineral content with Hologic(R)
      QDR-4500. Body fat percentage was calculated using a four-compartment model.
      RESULTS: Compared with body fat percentage (BF%) obtained using the reference
      method, BF% for the Singaporean Chinese, Malays and Indians were under-predicted
      by BMI, sex and age when an equation developed in a Caucasian population was
      used. The mean prediction error ranged from 2.7% to 5.6% body fat. The BMI/BF%
      relationship was also different among the three Singaporean groups, with Indians
      having the highest BF% and Chinese the lowest for the same BMI. These differences
      could be ascribed to differences in body build. It was also found that for the
      same amount of body fat as Caucasians who have a body mass index (BMI) of 30
      kg/m2 (cut-off for obesity as defined by WHO), the BMI cut-off points for obesity
      would have to be about 27 kg/m2 for Chinese and Malays and 26 kg/m2 for Indians.
      CONCLUSIONS: The results show that the relationship between BF% and BMI is
      different between Singaporeans and Caucasians and also among the three ethnic
      groups in Singapore. If obesity is regarded as an excess of body fat and not as
      an excess of weight (increased BMI), the cut-off points for obesity in Singapore
      based on the BMI would need to be lowered. This would have immense public health
      implications in terms of policy related to obesity prevention and management.

PMID- 10951541
TI  - The correlates of long-term weight loss: a group comparison study of obesity.
AB  - OBJECTIVE: Although the majority of weight loss attempts are unsuccessful, a
      small minority succeed in both weight loss and maintenance. The present study
      aimed to explore the correlates of this success. METHOD: A group comparison
      design was used to examine differences between women who were classified as
      either weight loss maintainers (had been obese (body mass index, BMI=30+ kg/m2)
      and had lost weight to be considered non-obese (BMI<30 kg/m2) and maintained this
      weight loss for a minimum of 3 y; n=44), stable obese (maintained an obese weight
      (BMI=30+ kg/m2) for longer than 3 y; n=58), and weight loss regainers (been obese
      (BMI=30+ kg/m2), lost sufficient weight to be considered non-obese (BMI<30 kg/m2)
      and regained it (BMI=30+ kg/m2), n=40). In particular, the study examined
      differences in profile characteristics, historical factors, help-seeking
      behaviours and psychological factors. RESULTS: The results showed that in terms
      of profile and historical factors, the weight loss maintainers had been lighter,
      were currently older and had dieted for longer than the other groups but were
      matched in terms of age, class and ethnic group. In terms of help-seeking
      behaviours, the weight loss maintainers reported having tried healthy eating more
      frequently but were comparable to the other subjects in terms of professionals
      contacted. Finally, for psychological factors the weight loss maintainers
      reported less endorsement for medical causes of obesity, greater endorsement for
      psychological consequences and indicated that they had been motivated to lose
      weight for psychological reasons. CONCLUSIONS: Weight loss and maintenance is
      particularly correlated with a psychological model of obesity. This has
      implications for improving the effectiveness of interventions and the potential
      impact of current interest in medical approaches to obesity.

PMID- 10951542
TI  - Critical value for the index of body fat distribution based on waist and hip
      circumferences and stature in obese girls.
AB  - OBJECTIVE: To determine the critical value for the standard deviation score (SDS)
      of waist-hip ratio (WHR)/height (Ht), as an age-adjusted measure of body fat
      distribution, in relation to occurrence of biochemical complications in obese
      girls. DESIGN: Cross-sectional, clinical study. The (WHR/Ht)-SDS was calculated
      as described previously. Obese girls were classified into two groups according to
      the occurrence of abnormal values in either serum triglyceride, alanine
      aminotransferase or insulin level. The criteria for obesity were subjected to the
      receiver operating characteristic (ROC) analysis. SUBJECTS: One-hundred and
      twenty-four outpatient Japanese obese girls, ranging in age from 9 to 15 y.
      MEASUREMENTS: Height, body weight, waist girth and hip girth as anthropometric
      measures. Percentage overweight, waist girth, WHR and (WHR/Ht)-SDS as criteria
      for obesity. Clinical laboratory analysis for fasting blood samples of obese
      children. RESULTS: Fifty-nine girls were classified into the no complication
      group, and 65 girls into the complication group. Those with complications were
      older, more obese, and their waist girth and WHR were larger, than the girls
      without complications. The (WHR/Ht)-SDS was >2-fold higher and lipoprotein
      profile was more atherogenic in the complication group than in the no
      complication group. Among the four criteria of obesity, (WHR/Ht)-SDS gave the ROC
      curve skewed furthest into the top left corner of the diagram. Both sensitivity
      and specificity for (WHR/Ht)-SDS were >80% at the critical value of 2.00. The
      sensitivity for waist girth was as high as that for specificity for the rest of
      the criteria were <80%. CONCLUSION: Only (WHR/Ht)-SDS showed high enough
      sensitivity and specificity to predict metabolic derangement in the present obese
      girls. (WHR/Ht)-SDS can serve as the diagnostic criterion that classifies obesity
      in Japanese adolescent girls into two types.

PMID- 10951543
TI  - The relation between dietary change and rising US obesity.
AB  - OBJECTIVE: To determine if the source from which food is obtained has contributed
      to the increased obesity of the US population, while controlling for demographic,
      lifestyle and regional factors. METHODS: Multiple regression was used to estimate
      the effect of food source on body mass index (BMI) while accounting for other
      factors which have been shown to affect obesity in a nationally representative
      sample of the US population. SAMPLE: This study used secondary data from the 1994
      1996 Continuing Survey of Food Intake by Individuals (CSFII). The CSFII is a
      nationally representative sample of 16,103 individuals, obtaining for each
      respondent 24 h recalls of all food intake on two nonconsecutive days as well as
      demographics and information on lifestyle choices. RESULTS: For a large number of
      demographic and lifestyle factors, our results support those which have
      previously been found to contribute to increased overweight. Our contribution is
      to examine whether the source from which food is obtained also contributes to
      increased overweight. Our evidence suggests that this is the case. The average
      height for males in our sample was 1.77 m. For two such males, one who ate food
      away from home (FAFH) during the previous 24 h period and the other who did not,
      results suggest that the first will be about 1 kg heavier, all other factors
      being equal. For two females of average height (1.63 m) the same is true for
      those who ate fast food, but not at restaurants. In all cases, except females who
      ate at restaurants, the effects are significant in the regression (P<0.05).
      CONCLUSION: The trends in both increased US obesity and in increased consumption
      of FAFH are unlikely to be coincidental. FAFH, and particularly fast food
      consumption, are likely to be contributing factors to increased obesity.

PMID- 10951544
TI  - Functional and histological characteristics of skeletal muscle and the effects of
      leptin in the genetically obese (ob/ob) mouse.
AB  - BACKGROUND: Skeletal muscle mass in genetically obese (ob/ob) mice displays a
      reduced mass compared with their normal lean counterpart mice. However, the
      functional capacity of the available skeletal muscle mass in these animals has
      not yet been determined. OBJECTIVE: To investigate the properties of skeletal
      muscle in ob/ob mice and determine the effects of leptin administration on
      skeletal muscle in these mice. METHODS: Following 4 weeks of i.p. leptin
      administration (or control treatment) anaesthetized ob/ob and lean mice had their
      extensor digitorum longus and soleus muscles removed, and standard measures of
      isometric contractile properties and fatigability were performed. Histochemistry
      was used to determine fibre type proportions and individual fibre areas of all
      muscles. RESULTS: Leptin had no effect on the morphology or function of ob/ob
      skeletal muscle despite reducing body mass in ob/ob mice. Force production was
      unaltered in obese mice. However, a significant prolongation of contraction and
      relaxation times were evident. Obese skeletal muscle was also more fatigue
      resistant. Fibre proportions displayed a more slow type profile in ob/ob skeletal
      muscle, and in conjunction with previous work a reduced ability to hypertrophy.
      CONCLUSION: Skeletal muscle from obese mice is morphologically and functionally
      different from lean mouse skeletal muscle. Obese muscle is very similar to
      skeletal muscle from aged mice, and the specific contractile properties examined
      appear to be determined by the fibre make-up of these muscles.

PMID- 10951545
TI  - Intrapair resemblance in very low calorie diet-induced weight loss in female
      obese identical twins.
AB  - OBJECTIVE: To assess intrapair resemblance in changes of body weight, total body
      fat, fat distribution, resting metabolic rate, fasting respiratory quotient and
      cardiovascular disease risk factors in response to therapeutic weight loss in
      female obese identical twins. DESIGN: Patients stayed for 40 days on an inpatient
      metabolic unit under careful supervision. The stay was divided into three parts:
      an initial period of 7 days for adjustment to the hospital environment and for
      baseline measurements, 28 days of the weight reduction regimen when negative
      energy balance was achieved mainly by a very low calorie diet (1.6 MJ per day)
      and 5 days of testing after weight reduction. SUBJECTS: Fourteen pairs of
      premenopausal female obese identical twins (age: 39.0+/-1.7 y; body weight (BW):
      93.9+/-21.2 kg; body mass index (BMI): 34.2+/-7.8 kg/m2) participated in the
      study. MEASUREMENTS: Before and after weight loss, the following measurements
      were made: body composition by anthropometry and hydrodensitometry, intra
      abdominal fat by ultrasonography, resting metabolic rate by indirect calorimetry.
      Total cholesterol, high-density lipoprotein-cholesterol, triglycerides and uric
      acid were determined by standard laboratory procedures. Blood pressure was
      measured in the morning in the recumbent position. RESULTS: Subjects lost 8.8+/
      1.9 kg of weight, from 93.9+/-21.2 to 85.1+/-10.9 kg (P<0.0001) and 6.5+/-2.3 kg
      of body fat (P<0.001). Weight losses varied widely among subjects, with a high
      correlation between losses of members of twin pairs for body weight (r=0.85;
      P<0.001) and for body fat (r=0.88; P<0.0001). Changes in uric acid resulting from
      weight loss were also correlated among members of twin pairs whereas changes in
      blood pressure, cholesterol and triglycerides were not. CONCLUSION: The great
      intrapair resemblance observed in very low calorie diet-induced weight and fat
      losses in female obese identical twins suggests an important role of genetic
      factors in response to the weight reduction regimen.

PMID- 10951546
TI  - The relationship between body mass index and waist circumference: implications
      for estimates of the population prevalence of overweight.
AB  - OBJECTIVE: Body mass index (BMI) based on self-reported height and weight is a
      systematically biased, but acceptable measure of adiposity and is commonly used
      in population surveys. Recent studies indicate that abdominal obesity is more
      strongly associated with obesity-related health problems than is adiposity
      measured by BMI. The purpose of this study was to determine the relationships of
      both measured and self-reported BMI with measured waist circumference in a
      randomly selected sample of Australian adults. DESIGN: Cross-sectional survey
      with self-reported and laboratory-based measures of adiposity. SUBJECTS: 1140
      randomly-selected Australian adults aged 18-78 y resident in the city of
      Adelaide, South Australia. MEASUREMENTS: Data on self-reported and measured
      height and weight as well as measured waist circumference were drawn from the
      Pilot Survey of the Fitness of Australians database. The proportion of men and
      women with acceptable BMI (BMI</=25 kg/m2) and with excess abdominal adiposity
      (>/=94 cm for men and >/=80 cm for women) was determined. Differences in the
      prevalence of overweight based on BMI alone or BMI and waist circumference were
      also determined. RESULTS: Compared with the prevalence based on self-reported BMI
      alone, the prevalence of overweight among men based on self-reported BMI and
      waist circumference combined was 2.4%, 5.3%, 19.1% and 7.5% greater for men aged
      18-39 y, 40-59 y, 60-78 y and for all men, respectively. Among women, compared
      with the prevalence based on self-reported BMI alone, the prevalence of
      overweight based on the combined measures was 9.9%, 24.0%, 33.3% and 20.6%
      greater for women aged 18-39 y, 40-59 y, 60-78 y and for all women, respectively.
      CONCLUSIONS: If waist circumference is used as the criterion, then the prevalence
      of overweight among Australian adults, and probably other Caucasian populations,
      may be significantly greater than indicated by surveys relying on self-reported
      height and weight. The development of valid self-reported measures of waist
      circumference for use in population surveys may allow more accurate
      epidemiological monitoring of overweight and obesity.

PMID- 10951547
TI  - Gender, obesity, hepatic nuclear factor-1alpha G319S and the age-of-onset of type
      2 diabetes in Canadian Oji-Cree.
AB  - Among the Oji-Cree of northern Ontario, women have both a higher prevalence and
      an earlier onset of type 2 diabetes compared to men. We studied the relationship
      between HNF1A S319 and both the presence of and the age-of-onset of type 2
      diabetes in women and men separately. We found that: 1) in women, there was a
      significant difference in the mean age-of-onset of type 2 diabetes according to
      HNF1A genotype; and 2) in men, there was no difference in the mean age-of-onset
      of type 2 diabetes according to HNF1A genotype. The findings indicate that HNF1A
      S319 is associated with increased susceptibility to type 2 diabetes in both men
      and women, but with earlier age-of-onset in women only. One factor that might
      account for the gender difference in the onset of HNF1A S319-associated type 2
      diabetes is the greater prevalence and severity, and earlier onset of, obesity
      among female Oji-Cree.

PMID- 10951549
TI  - The perceived relative worth of reaching and maintaining goal weight.
AB  - OBJECTIVE: To examine the perceived relative worth of reaching and maintaining a
      self-selected goal weight, for obese and non-obese individuals. DESIGN: Cross
      sectional study. SUBJECTS: Twenty-five obese treatment-seekers (age 41.0 y, BMI
      42.5) and a community sample of 31 obese (age 40.8 y, BMI 32.2) and 64 non-obese
      participants (age 32.4 y, BMI 23.4). MEASUREMENT: An 18-item forced-choice
      questionnaire evaluating what participants would hypothetically sacrifice to
      reach and maintain their goal weight. RESULTS: Most obese treatment-seekers would
      hypothetically endure much to achieve their desired weight. For example, 88% or
      more would forego a job promotion, retiring with full-pay, eliminating the
      national debt, or winning their dream house or car or an all-expense-paid
      vacation, and smaller majorities would suffer loss of half their income or a job
      demotion. Many non-treatment-seeking obese would forfeit future rewards to reach
      goal weight, but fewer would incur negative events. About a third of non-obese
      participants would forgo certain positive events, but few would suffer an adverse
      event to achieve goal weight. Within the combined obese sample, females viewed
      attaining goal weight as more important than did males, but there were no
      significant racial differences. An index of overall worth of weight goal was
      related positively to current weight and BMI and negatively to goal weight as
      percentage of current weight (P<0.01). CONCLUSION: Excessive value may be placed
      on attaining less than realistic weight goals, particularly but not exclusively
      by treatment-seeking and heavier obese people and those who desire greater weight
      loss. Clinicians should take this phenomenon into consideration, and public
      health initiatives should attempt to place body weight in a more balanced
      perspective.

PMID- 10951548
TI  - Linkage exclusion analysis of the chromosome 11 region containing UCP2 and UCP3
      with obesity-related phenotypes in Mexican Americans.
AB  - OBJECTIVE: To investigate whether the region of chromosome 11 (11q13) containing
      the genes UCP2 and UCP3 could be excluded for linkage with a variety of obesity
      related phenotypes in humans. DESIGN: Exclusion mapping using a variance
      component approach in extended pedigrees. SUBJECTS: Four-hundred and fifty eight
      individuals (195 females, 263 males) distributed in 10 Mexican American families
      of probands randomly ascertained with respect to any disease state and who are
      participating in the San Antonio Family Heart Study. Ages range from 18 to 87
      (mean age 35 y). MEASUREMENTS: Serum leptin levels, fat mass (FM), body mass
      index (BMI), and waist circumference. RESULTS: We were able to exclude the
      chromosomal region containing UCP2/UCP3 as having an effect on this set of
      obesity-related phenotypes at relative effect sizes of 10% or greater (P
      values<0.05). CONCLUSIONS: These results suggest that variation in these genes is
      unlikely to have a substantial effect on the expression of obesity-related
      phenotypes in the Mexican American population.

PMID- 10951550
TI  - Socio-demographic variables and 6 year change in body mass index: longitudinal
      results from the GLOBE study.
AB  - BACKGROUND: Body mass index (BMI) differs by socio-demographic variables, but the
      origin of these associations remains relatively unknown. OBJECTIVE: To
      investigate the association between socio-demographic variables and the
      subsequent change in BMI over six years. DESIGN: A Dutch prospective cohort study
      (GLOBE) from which data were used from initially 20-49-year-old subjects (males:
      n=362; females: n=405). BMI was calculated from self-reported body height and
      weight data obtained in 1991 and 1997. Socio-demographic variables used were sex,
      age, educational level and the occupational level of the main breadwinner, family
      income, marital status, religious affiliation and degree of urbanization and
      measured in 1991. RESULTS: Cross-sectionally, BMI was higher in males than in
      females. BMI was positively associated with age and negatively associated with
      educational level in both sexes, after adjustment for the other socio-demographic
      variables. A positive association of BMI with family income was found in males
      and a negative association with occupational level was found in females. During
      follow-up, BMI increased significantly more in females (from 23.0 (s.d. 3.3) to
      24. 2 (s.d. 3.8)) than in males (from 24.3 (s.d. 2.9) to 25.1 (s.d. 3. 5)). With
      the exception of a significant lesser increase in BMI in initially 30-39-year-old
      women compared to initially 40-49-year-old women, no other statistically
      significant associations were found between socio-demographic variables and the 6
      year change in BMI. CONCLUSIONS: Cross-sectional differences in BMI by socio
      demographic variables are not due to different 6-year changes in BMI for
      categories of these variables in adulthood. Cross-sectional differences in BMI by
      educational level are probably established at the end of adolescence.

PMID- 10951552
TI  - Neurovirulence of glycoprotein C(gC)-deleted bovine herpesvirus type-5 (BHV-5)
      and BHV-5 expressing BHV-1 gC in a rabbit seizure model.
AB  - Herpesvirus glycoprotein C (gC) is one of the major virus attachment proteins.
      Bovine herpesvirus type 1 (BHV-1) causes respiratory and genital diseases in
      cattle, whereas BHV-5 causes acute meningoencephalitis in calves. The gC gene
      sequence of these two viruses are substantially different. To determine the
      contribution of the BHV-5 glycoprotein gC (gC5) to the neuropathogenesis of BHV
      5, we have constructed two BHV-5 recombinants: gC-deleted BHV-5 (BHV-5gCDelta)
      and BHV-5 expressing BHV1 gC (BHV-5gC1). Neurovirulence properties of these
      viruses were analyzed using a rabbit seizure model that distinguishes BHV-1 and 
      5 based on their differential neuropathogeneses. Intranasal inoculations of BHV
      5gCDelta and BHV-5gC1 viruses produced neurological signs in 30% and 40% of the
      infected rabbits, respectively. Immuno-histochemistry results showed that the
      number of infected neurons was 2 - 4-fold less with the gC-deleted BHV-5 than
      with the wild-type BHV-5. The gC-deleted BHV-5 did not invade the hippocampus but
      invaded additional sites not invaded by wild-type BHV-5. Similarly, the BHV-5gC1
      virus failed to invade the hippocampus, but it did not invade the additional
      sites. Virus isolation results suggest that these recombinants replicate less
      efficiently in the brain than the wild-type and gC-revertant viruses. However,
      compared to the gC-deleted BHV-5, the gC-exchanged BHV-5gC1 replicated better
      within the CNS. These results indicate that gC regulates BHV-5 neurotropism in
      some areas of the olfactory pathway. Additionally, gC is important for BHV-5
      neurovirulence in the olfactory pathway but it is not essential.

PMID- 10951551
TI  - Comparative molecular analysis of HTLV-I proviral DNA in HTLV-I infected members
      of a family with a discordant HTLV-I-associated myelopathy in monozygotic twins.
AB  - In order to elucidate the underlying mechanisms of a discordant case with HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) in monozygotic
      twins, we investigated HTLV-I tax sequences of 10 - 18 polymerase chain reaction
      based clones each derived from peripheral blood mononuclear cells of the twins as
      well as their infected mother and an elder brother who also suffered from
      HAM/TSP. Sequence comparison revealed that three of the infected individuals
      including a twin with HAM/TSP shared the consensus tax sequence identical to the
      reference, ATK-1, but that of another healthy twin was different at five
      nucleotide positions including three nonsynonymous changes from ATK-1. This
      finding strongly suggested that different HTLV-I strains infected the monozygotic
      twins and the difference in infected proviral sequences determined the discordant
      clinical outcomes. Transfection and subsequent reporter assays failed to show a
      significant difference in transactivation activity on HTLV-I LTR and NF-kappaB
      elements between the products of the two sequences. Two HAM/TSP patients (a twin
      and elder brother) among three members infected with the ATK-1 type virus shared
      a paternal HLA allele which was absent in the healthy individual (mother).
      Genetic analysis of sequence variation in the tax sequences of the discordant
      twins showed that the Dn/Ds ratio was high in the healthy twin but low in the
      twin with HAM/TSP, implying the presence of more intense selection forces in the
      carrier. Our findings strongly suggested that a particular combination of HTLV-I
      strains with an HLA genotype would be a risk for HAM/TSP.

PMID- 10951553
TI  - Herpesvirus quiescence in neuronal cells: antiviral conditions not required to
      establish and maintain HSV-2 quiescence.
AB  - We previously described a novel in vitro model of a non-productive herpes simplex
      virus type 1 (HSV-1) infection in neurally differentiated (ND)-PC12 cells that
      allows for inducible virus replication upon forskolin and heat stress (HS)
      treatment. In this research, we further characterized the model with respect to
      HSV-2 strain 333. We found that: (i) ND-PC12 cells are non-permissive to HSV-2
      replication; (ii) HSV-2 can establish a quiescent infection, like HSV-1, in ND
      PC12 cells with the transient use of acycloguanosine (ACV); however unlike HSV-1,
      anti-viral conditions are not obligatory to establish and maintain a quiescent
      state; (iii) the quiescent state is maintained in the presence of Vero cell
      cocultivation indicating that such cultures are free of infectious virus; and
      (iv) a high percentage of quiescently infected (QIF)-PC12 cell cultures (80 -
      100%) produce HSV-2 in response to forskolin and HS (43 degrees C, 3 h) treatment
      for as long as 4 weeks post infection. These findings indicate that ND-PC12 cells
      can harbor HSV-2 in a cryptic and non-productive state that is reversible. This
      model has appealing features for studying gene expression during the
      establishment, maintenance and reactivation phases of the HSV-2 quiescent state
      in cell culture.

PMID- 10951554
TI  - Asymptomatic herpes simplex type 1 virus infection of the mouse brain.
AB  - An asymptomatic and transitory brain infection takes place in adult Swiss CD-1
      mice after intranasal inoculation of HSV-1 strain SC16. Time course and
      distribution of the infection in the brain are demonstrated, (i) by titration of
      the nasal tissue and olfactory bulbs for 16 days post-infection (p.i.), showing a
      maximum production yield on day 7 p.i. and no replicating virus on day 16 p. i.;
      (ii) expression in the brain of the lac Z reporter gene of HSV-1 strain SC16
      DeltaUS5-lac Z consistent with a central spread of the virus through the central
      olfactory pathways and the trigeminal system as described in acute HSV-1
      encephalitis models; (iii) PCR amplifications of a segment of the thymidine
      kinase gene (HSV-tk) showing the persistence of viral genome in the nasal tissue
      and olfactory bulbs after clearance of infectious virus. The asymptomatic
      character of the infection is demonstrated over 2 months p.i. (i) by normal body
      weight; (ii) a neurological survey which excludes motor, sensory, balance and
      postural signs; (iii) two behavioral tests, the open-field test for exploratory
      activity and the cookie-finding test for olfactory search. On the other hand,
      intracerebral inocula cause encephalitis and death in a few days (LD50 ca. 14
      p.f.u.). Intracranial, surgical transection of one olfactory nerve does not
      prevent infection of the corresponding bulb nor does it modify virus
      distribution, suggesting multiple entry routes from the nasal cavity to the
      brain. In conclusion, HSV-1 strain SC16 reaches the brain of CD-1 mice from the
      nasal cavity and replicates without neurological or behavioral signs.

PMID- 10951555
TI  - A hamster model of equine herpesvirus 9 induced encephalitis.
AB  - An acute and lethal infection of equine herpesvirus 9 (EHV-9), a new type of
      equine herpesvirus, was established in Syrian hamsters by intranasal inoculation.
      Clinical symptoms included the loss of body weight, nasal and ocular discharges
      and apparent neurological symptoms. Both LD50 and ID50 were equal at 33 plaque
      forming units. Histological and immunohistochemical examination demonstrated that
      the virus replicated in the olfactory mucosal cells and in the neurons of the
      olfactory bulbs, cerebrum and mesencephalon. The induction of encephalitis by
      intranasal but not by other routes of inoculation (i.v., i.p., i.m.) indicated
      that EHV-9 entered the brain via the olfactory nerve and then spread trans
      synaptically to connecting neurons along the olfactory tract. This animal model
      should be useful for studying the pathogenesis and neurovirulence of this newly
      discovered neurotropic virus as well as other neurotropic herpesviruses.

PMID- 10951556
TI  - Phenotypic characterisation and infection of ovine microglial cells with Maedi
      Visna virus.
AB  - Maedi-Visna Virus (MVV) infection of the central nervous system (CNS) results in
      pathological changes, the mechanisms of which are poorly understood. MVV
      preferentially infects cell of the monocyte/macrophage lineage in vivo. The
      neuroparenchymal microglial cells are the resident tissue macrophages in the CNS
      and therefore likely targets for MVV infection. However, no information is
      currently available on the susceptibility of these cells to MVV infection or
      their contribution to neuropathological changes as a result of MVV infection.
      Highly enriched primary ovine microglial cell cultures were set up from brain
      tissues of lambs. These cells were amoeboid or bipolar with spikes, a morphology
      consistent with microglial cells of other species, and stained positive for CD1,
      CD11a, CD11c, CD14, MHC-class I, MHC-class II, and beta-N-acetyl galactose, but
      not with markers of astrocytes or oligodendrocytes. These sheep microglial cells
      were permissive for MVV infection. Productive MVV infection resulted in selective
      transcriptional up-regulation of the pro-inflammatory cytokines TNFalpha and IL
      6. In contrast, there was no change in levels of transcripts for TGFbeta1, IL
      1beta, GM-CSF, IL-10, or IL-12. These data provide the first evidence that ovine
      microglial cells can support productive infection with MVV, and that this leads
      to a selective up-regulation of proinflammatory cytokines. These may contribute
      to visna neuropathology.

PMID- 10951557
TI  - Changes in the N- and C-terminal sequences of the murine R7 Gag-tMos protein
      affect brain lesion induction.
AB  - Our preliminary studies suggested that the novel gag-truncated mos (tmos) open
      reading frame (ORF) of R7, a spontaneous deletion mutant of Moloney murine
      sarcoma virus 124 (MoMuSV124), may be responsible for R7's unique ability to
      induce brain lesions in all R7-injected mice. However, when we replaced the gag
      tmos ORF with either the MoMuSV124 or the homologous myeloproliferative sarcoma
      virus env-mos gene, we found that both recombinant viruses also induced brain
      lesions in all injected mice. Although these studies suggested that the critical
      determinants for brain lesion induction may reside in the tmos sequence common to
      all three viruses, they did not demonstrate if the N-terminus of Mos was
      dispensable for this activity. By inserting the FLAG sequence at the 3' end of
      the R7 gag-tmos ORF, we demonstrated that R7 does synthesize a Gag-tMos fusion
      protein. Using R7 gag deletion mutants with and without the FLAG sequence, we
      further demonstrated that (i) deletion of the entire gag sequence abolished R7's
      transforming activity; (ii) the ability of the virus to transform cultured
      NIH/3T3 cells was significantly reduced only when most of gag was deleted; (iii)
      the ability of the virus to induce brain lesions was inversely proportional to
      the extent of its gag deletions; and (iv) the insertion of FLAG at the Mos C
      terminus did not reduce the in vitro transforming activity of the FLAG-tagged
      viruses but did reduce their ability to induce brain lesions. Thus, we have
      demonstrated that altering the N- or C-terminus of the R7 Gag-tMos fusion protein
      can affect disease manifestation.

PMID- 10951558
TI  - The HSV 1 genome in quiescently infected NGF differentiated PC12 cells can not be
      stimulated by HSV superinfection.
AB  - This study reports that quiescent herpes simplex virus (HSV) type 1 genomes,
      persisting in long-term infected nerve growth factor (NGF) differentiated PC12
      cells, were not stimulated by superinfection with a HSV-1. We have previously
      shown that HSV-1 can establish long term, quiescent infections in NGF
      differentiated PC12 cells. To determine if virion associated factors or virus
      induced gene products could trans-activate the quiescent viral genomes, long term
      infected PC12 cell cultures were superinfected at a high moi (moi of 20) with a
      recombinant HSV 17alpha47/lacZ that contains the lacZ gene within the alpha 47
      locus. Progeny virus and gene expression from the resident 'quiescent' viral
      genomes were not detected following superinfection with recombinant
      17alpha47/lacZ. The failure to stimulate the quiescent genome appears to be
      related to the inability of the super infecting virus to induce any gene
      expression from its own genome following entry into the long term NGF treated
      PC12 cells. Interestingly, both primary and superinfecting viruses could be
      stimulated from the quiescently infected cultures following cocultivation with
      inducer cells. These data suggest that (i) HSV genomes in quiescently infected
      PC12 cells are unable to be stimulated by incoming virion associated factors and
      (ii) NGF differentiated PC12 cells maintained in tissue culture for longer than 3
      weeks became completely refractory to viral gene expression. The possibilities
      that these results are reflective of populations of neural cells, in vivo in
      mouse central nervous system, which are completely refractory to virus gene
      expression, yet accommodating to the maintenance of viral genomes and thus favor
      'latency', are discussed.

PMID- 10951560
TI  - Response.

PMID- 10951559
TI  - Long-term effects of HTLV-1 on brain astrocytes: sustained expression of Tax-1
      associated with synthesis of inflammatory mediators.
AB  - HTLV-1 is the causative agent of a chronic neurological disease, TSP/HAM. The
      persistently activated CTL response to the viral protein Tax-1 suggests the
      existence of persistent viral replication with continuous expression of Tax-1.
      Although CD4+ T-cell is the main target for HTLV-1, previous observations have
      indicated that the astrocyte, the major neural cell in close contact with blood
      vessel and thus with HTLV-1-infected T-cells infiltrating the CNS, may also be
      infected. We tested in vitro the hypothesis of persistent/restricted infection in
      human and rat astrocytes after transient contact with an infectious T-cell line
      (C91PL). Long-term analysis showed prolonged expression of Tax-1 in astrocytes,
      associated with secretion of inflammatory mediators (TNFalpha, IL1alpha, MMP-2,
      and MMP-9). These data suggest a possible contribution of Tax-1-expressing
      astrocytes to TSP/HAM pathogenesis.

PMID- 10951561
TI  - A choice between transcriptional enhancement and repression by the v-erbA
      oncoprotein governed by one nucleotide in a thyroid hormone responsive half site.
AB  - The v-erbA oncoprotein (P75gag-v-erbA) can repress thyroid hormone receptor
      induced transcriptional activation of target genes. A central question is how
      hormone responsive elements in a target gene determine the transcriptional
      regulation mediated by P75gag-v-erbA. We addressed this with receptors chimeric
      between P75gag-v-erbA and thyroid hormone receptor (TR) by testing their
      regulatory activities on thyroid hormone response elements (TREs) differing in
      the sequence of the consensus core recognition motif AGGTCA. We report here that
      enhances, TR dependent transcriptional activation is conferred by P75gag-v-erbA
      when the thymidine in the half site recognition motif is exchanged for an
      adenosine. The enhancement was independent of the DNA binding region of P75gag-v
      erbA, whereas increased expression of corepressor abolished the enhancing effect.
      The data indicate that the enhancement results from an impaired DNA binding by
      the oncoprotein combined with an effective scavenging of corepressors. Our data
      thus suggest the P75gag-v-erbA indirectly can contribute to enhancement of
      thyroid hormone induced gene expression.

PMID- 10951562
TI  - Sam68, RNA helicase A and Tap cooperate in the post-transcriptional regulation of
      human immunodeficiency virus and type D retroviral mRNA.
AB  - Unlike cellular mRNA, retroviral mRNA bypasses the tight coupling of the splicing
      and nuclear export steps to allow the export of intron-containing viral RNA
      transcripts to the cytoplasm. Two distinct nuclear export pathways for retroviral
      mRNA have been described: a CRM-1 dependent pathway mediated by the HIV-1 Rev
      protein and the Rev Response Element (RRE), and a CRM-1 independent pathway
      mediated by the Constitutive Transport Element (CTE) of type D retroviruses. Two
      CTE-binding proteins, RNA helicase A (RHA) and Tap, have been implicated in the
      nuclear export of CTE-containing RNA. Recently, we reported that expression of
      RRE-containing RNA could also be mediated by a cellular protein, Sam68,
      independently of Rev. Here we report evidence that Sam68, RHA and Tap cooperate
      in the nuclear export of both CTE- and RRE-containing RNA. RHA binds to Sam68 and
      to Tap both in vivo and in vitro. Over-expression of Sam68 activates both RRE-
      and CTE-regulated reporter gene expression in human cells and in quail cells in
      the presence of human Tap. This activation was competitively inhibited by the
      nuclear transport domain (NTD) of RHA and a transdominant negative mutant of Tap.
      Conversely, the activation of CTE by Tap in quail cells was inhibited by a
      transdominant mutant of Sam68 and NTD. We propose that both HIV and type D
      retroviruses may access the same constitutive RNA nuclear export pathway
      involving RHA, Tap and Sam68, even though HIV also utilizes the Rev protein for
      more efficient nuclear export. it is likely that this constitutive export pathway
      is also used by cellular mRNA, but at a different interface with the splicing
      process.

PMID- 10951563
TI  - Gros1, a potential growth suppressor on chromosome 1: its identity to basement
      membrane-associated proteoglycan, leprecan.
AB  - By immunoscreening with an antibody raised against a plasma membrane protein, we
      have cloned a growth suppressor gene, Gros1 and assigned it to short arm of human
      chromosome 1. Two alternatively spliced forms of the gene encoding 84- and 41-kDa
      (carboxy-terminus truncated) proteins were cloned. The two transcripts, 4.4 and
      2.7 kb, were expressed weakly in most of the human tissues, with a high
      expression of the smaller transcript in placenta, ovary and testis. Normal human
      fibroblasts in culture showed two transcripts, with a higher level of expression
      of the 4.4 kb transcript. Transformed cells on the other hand showed predominant
      expression of the 2.7 kb transcript. Two Gros1 transcripts were also detected in
      most of the mouse tissues. Stable transfection of the mouse cDNA encoding the 85
      kDa protein into NIH3T3 cells resulted in their slow growth and reduced colony
      forming efficiency. Stable clones expressing antisense RNA on the other hand
      exhibited higher colony forming efficiency. While our data implied that Gros1 is
      a novel growth suppressor gene on human chromosome 1, an independent study has
      recently characterized its rat-homolog as a leucine proline-enriched novel
      basement membrane-associated proteoglycan leprecan. We describe here cloning,
      expression and biological activity analysis implying that this novel proteoglycan
      is a potential growth suppressor on chromosome 1p31, frequently altered in many
      malignancies.

PMID- 10951564
TI  - Nuclear import and subnuclear localization of the proto-oncoprotein ETO (MTG8).
AB  - ETO (MTG8) was first described due to its involvement in the (8;21) translocation
      frequently observed in acute myeloid leukemias. In the t(8;21) the AML1 gene on
      chromosome 21 is fused to ETO on chromosome 8. The resultant hybrid protein is
      comprised of the DNA binding domain of AML-1 and the majority of ETO. This study
      examines the subnuclear distributions of ETO, AML-1B and AML-1/ETO proteins fused
      to green fluorescence protein in living cells using fluorescence microscopy.
      Further, we identified a 40 amino acid portion of ETO (amino acids 241-280) that
      was sufficient to cause nuclear import of green fluorescent protein. Mutational
      analysis demonstrated that lysine 265 and/or arginine 266 were required for
      nuclear import of ETO, but that the surrounding basic residues were not critical.
      ETO interacted with the nuclear import proteins importin-alpha and beta in vitro,
      and mutations in ETO that abolish nuclear localization also abolished the in
      vitro interaction with importin-alpha and beta. These data suggest that ETO
      enters the nucleus via an importin-mediated pathway. Additionally, ETO and AML
      1/ETO co-localized to punctate nuclear bodies distinct from those containing
      promyelocytic leukemia protein. Nuclear body formation was dependent upon a
      region of ETO N-terminal to the nuclear localization signal. Thus, ETO and AML
      1/ETO reside in potentially novel subnuclear compartments.

PMID- 10951565
TI  - The retinoblastoma protein is an essential mediator that links the interferon
      inducible 204 gene to cell-cycle regulation.
AB  - We have previously demonstrated that overexpression of p204, a member of the Ifi
      200 gene family, inhibits growth, delays G0/G1 progression into S phase, and
      impairs E2F-mediated transcriptional activity. In this study, we show that p204
      directly binds the retinoblastoma protein (pRb) in vivo to exert its activity.
      Transient p204 overexpression in Rb+/+ mouse embryo fibroblasts (MEF) inhibits
      cell proliferation, but does not affect cell growth in MEF derived from Rb-/-
      mice. Two human cell lines, Saos2 and C33A, bearing an inactive pRb, but not
      primary human embryo fibroblasts, are resistant to the p204 antiproliferative
      activity. p204 contains two 200 amino acid motifs, designated as type a or b
      domains, each containing a canonical Rb binding motif (LXCXE). When dominant
      negative mutants at the Rb binding motif were transfected in Rb+/+ MEF, p204 lost
      its ability to inhibit cell growth, delay cell transition from G1 to S phase, and
      impair DNA synthesis. Moreover p204 overexpression in Rb+/+ MEF led to a
      significant decrease of both DHFR and PCNA proteins, two S phase markers. By
      contrast, this effect was not observed when Rb+/+ MEF were transfected with a
      p204 mutated at both Rb binding sites. Finally, overexpression of the LXCXE p204
      mutant rendered Rb+/+ MEF resistant to the IFN-alpha antiproliferative activity,
      in comparison to the untransfected Rb+/+ MEF. As expected, Rb-/- cells were
      unsensitive to the IFN-alpha induced growth inhibition. Taken as a whole, these
      results suggest that (i) p204 contributes to the IFN-alpha antiproliferative
      activity and (ii) the primary target of p204 leading to efficient G1 arrest as
      well as to blockade of DNA replication from G1 phase is the pRb regulatory
      system.

PMID- 10951566
TI  - Cyclic AMP activates Ras.
AB  - In addition to protein kinase A (PKA), cAMP regulates the activity of cAMP-gated
      channels and Rap1-specific guanine nucleotide exchange factors. We tested the
      hypothesis that the targets of cAMP might also include regulators of the Ras
      protooncogene. In rat thyroid cells, thyrotropin (TSH) stimulates proliferation
      through a cAMP-mediated pathway that requires Ras activity. Interference with Ras
      impairs DNA synthesis stimulated by TSH as well as cAMP elevating agents and
      analogs, demonstrating that the requirement for Ras lies down-stream of cAMP.
      Although cAMP stimulates proliferation, microinjection of the purified PKA
      catalytic subunit failed to do so, suggesting that factors in addition to PKA are
      required for cAMP-stimulated cell cycle progression. When added to thyroid cells
      expressing human Ha-Ras, TSH rapidly and markedly increased the proportion of GTP
      bound Ras. Ras activity was increased within 1 min of TSH addition, maximal at 5
      15 min, and declined to basal levels 30-60 min after hormone treatment. Cyclic
      AMP elevating agents elicited similar effects on Ras, indicating that TSH
      activates Ras through a cAMP-mediated pathway. Although cAMP-mediated, Ras
      activation by TSH and cAMP was independent of PKA activity. Moreover, cAMP
      stimulated Ras activation was not impaired by tyrosine kinase inhibitors. These
      results indicate that cAMP activates targets in addition to PKA in thyroid cells,
      and that these targets may include regulators of Ras. The ability of cAMP
      elevating agents to activate Ras in addition to PKA may explain the inability of
      the PKA catalytic subunit to stimulate DNA synthesis in thyroid cells.

PMID- 10951567
TI  - A different function for a critical tryptophan in c-Raf and Hck.
AB  - The similarity of the catalytic domains of Raf and Src family members suggests
      that functions of homologous residues may be similar in both kinase families. A
      tryptophan residue, W260, in the WEI region of the Src family kinase Hck has an
      important role in regulating ATP binding. We tested the hypothesis that the
      tryptophan, W342, in the WEI region of c-Raf may have a similar role to the W260
      of Hck. Mutation of W260 to A in Hck activates kinase activity, but we found that
      mutation of W342 to A in c-Raf inactivates the kinase activity. Mutating W342 to
      aspartate (D), lysine (K) or histidine (H) also inactivated c-Raf whether assayed
      as a purified immunoprecipitate or when recruited to the plasma membrane. A
      constitutively active c-Raf can be generated by mutating two regulatory tyrosines
      to aspartate. When placed into this active c-Raf mutant, mutation of W342 to D, K
      or H enabled phosphorylation and activation of the c-Raf substrate MEK at the
      plasma membrane but not in an immunoprecipitation assay. We conclude that (1)
      Tryptophan has a different role in the WEI regions of c-Raf and Hck, (2) W342 is
      not directly involved in MEK binding as both positive and negative residues at
      342 are permissive for MEK activation at the membrane in a constitutively active
      c-Raf mutant, (3) Factors at the membrane are capable of potentiating activation
      of c-Raf containing mutated W342 in a hyperactivated c-Raf, but not in a wild
      type c-Raf and (4) There is a stringent structural requirement for W at residue
      342 in c-Raf.

PMID- 10951568
TI  - Aberrant cell cycle progression contributes to the early-stage accelerated
      carcinogenesis in transgenic epidermis expressing the dominant negative
      TGFbetaRII.
AB  - Mutations in the transforming growth factor beta type II receptor (TGFbetaRII)
      have been found in various malignant tumors, suggesting that loss of TGFbeta
      signaling plays a causal role in late-stage cancer development. To test whether
      loss of TGFbetaRII is involved in early-stage carcinogenesis, we have generated
      transgenic mice expressing a dominant negative TGFbetaRII (deltabetaRII) in the
      epidermis. These mice exhibited an increased susceptibility to chemical
      carcinogenesis protocols at both early and late stages. In the current study,
      parameters for cell cycle progression and chromosome instability were analysed in
      deltabetaRII tumors. DeltabetaRII papillomas showed an increased S phase in flow
      cytometry. Bromodeoxyuridine (BrdU) labeling and mitotic indices in deltabetaRII
      papillomas also showed a threefold increase compared to papillomas developing in
      non-transgenic mice. When papillomas further progressed to squamous cell
      carcinomas (SCC), both control and deltabetaRII SCC showed similar BrdU labeling
      indices and percentages of S phase cells. However, deltabetaRII SCC cells showed
      a sixfold increase in the G2/M population. Mitotic indices in deltabetaRII SCC
      also showed a threefold increase compared to non-transgenic SCC. Consistent with
      a perturbed cell cycle, deltabetaRII papillomas and SCC showed reduced expression
      of the TGFbeta target genes p15 (INK4b), p21 (WAF-1) and p27 (Kip1), inhibitors
      of cyclin-dependent kinases (cdks). However, most deltabetaRII papilloma cells
      exhibited normal centrosome numbers, and deltabetaRII SCC exhibited a similar
      extent of centrosome abnormalities compared to control SCC (35-40% cells). Most
      of deltabetaRII SCC exhibited diploid chromosome profiles. These data indicate
      that inactivation of TGFbetaRII accelerates skin tumorigenesis at early stages by
      the acceleration of loss of cell cycle control, but not by increased chromosome
      instability.

PMID- 10951569
TI  - Human endothelial cells expressing polyoma middle T induce tumors.
AB  - The middle T oncogene of murine polyomavirus (PymT) rapidly transforms and
      immortalizes murine embryonic endothelial cells (EC), leading to the formation of
      vascular tumors in newborn mice, by recruitment of host, non-transformed EC.
      These tumors are reminiscent of human vascular tumors like cavernous hemangioma,
      Kaposi's sarcoma or those characterizing Kasabach-Merrit syndrome. Here we
      investigate the in vitro and in vivo behavior of human primary umbilical cord
      vein EC expressing PymT. While PymT has been unable to transform human
      fibroblasts in earlier experiments or controls done here, mT expressing EC (PymT
      EC) derived by infection with pLX-PymT retrovirus induce hemangiomas in nu/nu
      mice. These tumors contain not only human cells but also recruited mouse EC as
      shown by the presence of human and murine CD31 positive EC. In vitro analysis
      shows that PymT-EC retain endothelial specific markers like CD31, Von Willebrand
      factor, and VE-cadherin, and reach the confluence without signs of overgrowth.
      They are also responsive to vascular endothelial growth factor-A. However, their
      proliferation rate is increased. The balance between urokinase-type plasminogen
      activator and plasminogen activator inhibitor-1 is modified; RNA and catalytic
      activity for the former are elevated while PAI-1 RNA is reduced. In contrast with
      murine model, where the PymT EC cells become immortal, the effects induced by
      PymT in human EC are transient. After 12-15 passages, human PymT EC stop
      proliferating, assume a senescent phenotype, and lose the ability to induce
      hemangiomas. At the same time both the amount of middle T protein and the level
      of activation of pp60c-src lower.

PMID- 10951570
TI  - Distinct methylation patterns of two APC gene promoters in normal and cancerous
      gastric epithelia.
AB  - The adenomatous polyposis coli (APC) tumor suppressor gene is mutationally
      inactivated in both familial and sporadic forms of colorectal cancers. In
      addition, hypermethylation of CpG islands in the upstream portion of APC, a
      potential alternative mechanism of tumor suppressor gene inactivation, has been
      described in colorectal cancer. Because a subset of both gastric and colorectal
      cancers display the CpG island methylator phenotype, we hypothesized that
      epigenetic inactivation of APC was likely to occur in at least some gastric
      cancers. APC exhibits two forms of transcripts from exons 1A and 1B in the
      stomach. Therefore, we investigated CpG island methylation in the sequences
      upstream of exons 1A and 1B, i.e., promoters 1A and 1B, respectively. We
      evaluated DNAs from 10 gastric cancer cell lines, 40 primary gastric cancers, and
      40 matching non-cancerous gastric mucosae. Methylated alleles of promoter 1A were
      present in 10 (100%) of 10 gastric cancer cell lines, 33 (82.5%) of 40 primary
      gastric cancers, and 39 (97.5%) of 40 noncancerous gastric mucosae. In contrast,
      promoter 1B was unmethylated in all of these same samples. APC transcripts from
      exon 1A were not expressed in nine of the 10 methylated gastric cancer cell
      lines, whereas APC transcripts were expressed from exon 1B. Thus, expression from
      a given promoter correlated well with its methylation status. We conclude that in
      contrast to the colon, methylation of promoter 1A is a normal event in the
      stomach; moreover, promoter 1B is protected from methylation in the stomach and
      thus probably does not participate in this form of epigenetic APC inactivation.

PMID- 10951571
TI  - Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by
      X-ray irradiation.
AB  - Interleukin 3-dependent bone marrow and Ba/F3 cells present constitutive Fas
      expression. A dose dependent increase in Fas surface expression was induced in
      these cells by X-ray irradiation. Using primary cell cultures and established
      cell lines derived from p53-null mice (p53-/-), we demonstrated that the increase
      in Fas expression upon X-ray irradiation is dependent on the presence of at least
      one wild-type p53 allele. Fas induction by X-ray irradiation was negatively
      modulated by IL-3; an earlier Fas induction was observed in the absence of IL-3
      or at low IL-3 concentrations. However, IL-3 withdrawal in non-irradiated cells
      did not induce an increase in Fas expression. X-ray irradiation of Ba/F3 cells
      induced the expression of functional Fas receptors. Therefore, in IL-3-dependent
      cells, IL-3 regulates the rate of Fas expression, which is correlated with the
      degree of apoptosis observed in X-irradiated cells. Finally, we demonstrate that
      IL-3 controls the degree of Fas expression induced by irradiation through a p53
      mediated pathway.

PMID- 10951572
TI  - The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the
      mdm-2 binding site of the p53 tumour suppressor protein.
AB  - The tumour suppressor p53 protein integrates multiple signals regulating cell
      cycle progression and apoptosis. This regulation is mediated by several kinases
      that phosphorylate specific residues in the different functional domains of the
      p53 molecule. The human VRK1 protein is a new kinase related to a poxvirus
      kinase, and more distantly to the casein kinase 1 family. We have characterized
      the biochemical properties of human VRK1 from HeLa cells. VRK1 has a strong
      autophosphorylating activity in several Ser and Thr residues. VRK-1
      phosphorylates acidic proteins, such as phosvitin and casein, and basic proteins
      such as histone 2b and myelin basic protein. Because some transcription factors
      are regulated by phosphorylation, we tested as substrates the N-transactivation
      domains of p53 and c-Jun fused to GST. Human c-Jun is not phosphorylated by VRK1.
      VRK1 phosphorylates murine p53 in threonine 18. This threonine is within the p53
      hydrophobic loop (residues 13-23) required for the interaction of p53 with the
      cleft of its inhibitor mdm-2. The VRK1 C-terminus domain (residues 268-396) that
      contains a nuclear localization signal targets the protein to the nucleus, as
      determined by using fusion proteins with the green fluorescent protein. We
      conclude that VRK1 is an upstream regulator of p53 that belongs to a new
      signalling pathway.

PMID- 10951573
TI  - The interferon-induced protein kinase (PKR), triggers apoptosis through FADD
      mediated activation of caspase 8 in a manner independent of Fas and TNF-alpha
      receptors.
AB  - The interferon-induced dsRNA-dependent protein kinase (PKR) induces apoptosis of
      mammalian cells. Apoptosis induction by PKR involves phosphorylation of the
      translational factor eIF-2alpha and activation of the transcriptional factor NF
      kappaB, but caspase pathways activated by PKR are not known. Upregulation of Fas
      mRNA by PKR has been suggested to play a role in PKR-induced apoptosis. To learn
      how PKR induces apoptosis, we have analysed the role of molecules in death
      receptor pathways. We showed the involvement of the FADD-caspase 8 pathway on PKR
      induced apoptosis based on four experimental findings: upregulation of caspase 8
      activity during PKR-induced apoptosis, blocking of PKR-induced apoptosis by the
      use of a chemical inhibitor of caspase 8, and inhibition of PKR-induced apoptosis
      by expression of both a FADD dominant negative or a viral FLIP molecule.
      Significantly, despite the PKR-mediated upregulation of Fas mRNA expression, the
      Fas receptor-ligand pathway is not needed for PKR-induced apoptosis. Antibodies
      that inhibit TNFalpha-TNFR1 or Fas-FasL interactions were not able to block PKR
      induced apoptosis. Taken together, our observations establish the involvement of
      caspase 8 in PKR-induced apoptosis and suggest that death receptors other than
      Fas or TNFR1 or, alternatively, a novel mechanism involving FADD independently of
      death receptors, are responsible for PKR-induced apoptosis.

PMID- 10951575
TI  - Pim-1 kinase protects hematopoietic FDC cells from genotoxin-induced death.
AB  - The hematopoietic cell S/T kinase Pim-1 was originally discovered as a target of
      murine leukemia provirus integration, and when expressed at increased levels is
      predisposing to lymphomagenesis. Recently, Pim-1 has been shown to enhance the
      activities of p100, c-Myb and cdc25a, and in part this might explain reported
      effects on mitogenesis. In the context of cytokine withdrawal, Pim-1 also can
      attenuate programmed cell death (PCD). Cytokine withdrawal, however, alters
      signaling pathways and can complicate the dissection of mitogenic vs apoptotic
      responses. To better study possible effects of Pim-1 on PCD, a hematopoietic cell
      model was developed in which proliferation was supported efficiently by SCF plus
      EPO in the absence of endogenous Pim-1 gene expression. This was provided by
      factor-dependent FDCW2 cells that express endogenous and functional c-Kit, and
      were transfected stably with truncated Epo receptor form mutated at a Y343 STAT5
      binding site. In proliferating cells, exogenously expressed Pim-1 was observed to
      efficiently inhibit PCD as induced by either Co60 or adriamycin, and the dose
      dependent nature of this effect was established in several independent clones. By
      comparison, effects of exogenous Pim-1 on mitogenesis were nominal. In addition,
      in cell fractionation studies an estimated 25% of Mr 34000 Pim-1 (but not Mr
      44000 Pim-1) was present in nuclear extracts. Thus, Pim-1 efficiently buffers
      hematopoietic progenitor cells against death as induced by several clinically
      important apoptotic agents, and may directly target nuclear effectors.

PMID- 10951574
TI  - Oncostatin M and interleukin 6 inhibit cell cycle progression by prevention of
      p27kip1 degradation in HepG2 cells.
AB  - We analysed the regulation of G1-phase progression in relation to cytokine
      receptor signalling in HepG2 hepatoma cells, stably transduced with the IL-10
      receptor after stimulation with Oncostatin M (OSM), IL-6, Leukaemia Inhibitory
      Factor (LIF) and IL-10. All cytokines induced STAT3 phosphorylation to
      approximately the same level, but only OSM, and to a lesser extent IL-6, induced
      STAT5 phosphorylation. The cytokines also stimulated phosphorylation of ERK in
      the order of decreasing effectiveness: OSM > IL-6 > LIF > IL-10. The same order
      of activity of the cytokines was observed on inhibition of DNA synthesis and
      accumulation of cells in the G1-phase of the cell cycle. These processes were
      accompanied by a decrease in cyclin A expression and CDK2 activity, and enhanced
      accumulation of p27kip1. The level of p27kip1 mRNA expression was unaffected by
      the cytokines, and maintenance of the elevated level of p27kip1 occurred
      independently of de novo protein synthesis. Furthermore, inhibition of
      proteasomal activity increased the level of p27kip1 in the unstimulated cells to
      the same level as in OSM-treated cells. Inhibition of MEK activation completely
      abrogated OSM and IL-6 induced p27kip1 accumulation, while expression of dominant
      negative STAT5 decreased the OSM and IL-6 mediated inhibition of DNA-synthesis
      and partially inhibited p27kip1 accumulation.

PMID- 10951576
TI  - Synergistic activation of p53-dependent transcription by two cooperating damage
      recognition pathways.
AB  - High level activation of p53-dependent transcription occurs following cellular
      exposure to genotoxic damaging agents such as UV-C, while ionizing radiation
      damage does not induce a similarly potent induction of p53-dependent gene
      expression. Reasoning that one of the major differences between UV-C and ionizing
      radiation damage is that the latter does not inhibit general transcription, we
      attempted to reconstitute p53-dependent gene expression in ionizing irradiated
      cells by co-treatment with selected transcription inhibitors that alone do not
      activate p53. p53-dependent transcription can be dramatically enhanced by the
      treatment of ionizing irradiated cells with low doses of DRB, which on its own
      does not induce p53 activity. The mechanism of ionizing radiation-dependent
      activation of p53-dependent transcription using DRB is more likely due to
      inhibition of gene transcription rather than prolonged DNA damage, as the non
      genotoxic and general transcription inhibitor Roscovitine also synergistically
      activates p53 function in ionizing irradiated cells. These results identify two
      distinct signal transduction pathways that cooperate to fully activate p53
      dependent gene expression: one responding to lesions induced by ionizing
      radiation and the second being a kinase pathway that regulates general RNA
      Polymerase II activity.

PMID- 10951578
TI  - The contribution of the RING finger domain of MDM2 to cell cycle progression.
AB  - The MDM2 oncoprotein binds to p53 and abrogates p53-mediated G1 arrest and
      apoptosis. We show that MDM2 over-expression accelerates cell cycle progression
      of RPM12650 cells by overcoming the negative effect of endogenous wild type p53
      at the G1/S checkpoint. The interaction with p53 and transcription inhibition are
      necessary but not sufficient. The RING finger domain of MDM2 is also required for
      the positive effect of MDM2 on the cell cycle. Surprisingly, several point
      mutants in the zinc binding sites of the RING finger are fully competent for cell
      cycle stimulation even though they abolish MDM2-directed degradation of p53 and
      MDM2 E3-ligase activity. In contrast, alterations in and around the cryptic
      nucleolar localization sequence (KR motif) inhibit MDM2-mediated cell cycle
      progression as well as p53 degradation and MDM2 E3 ligase activity. We found that
      all the RING mutants decrease inhibition of both p53 dependent reporters and
      endogenous p21CIP1/WAF1/SDI1. These results indicate that the RING finger of MDM2
      has a role in the regulation of the cell cycle that is independent of p53
      degradation and endogenous p21CIP1/WAF1/SDI1 regulation.

PMID- 10951577
TI  - Redox regulation of p53 during hypoxia.
AB  - The transcription factor p53 can induce growth arrest or death in cells. Tumor
      cells that develop mutations in p53 demonstrate a diminished apoptotic potential,
      which may contribute to growth and tumor metastasis. Cellular levels of p53 are
      stabilized during hypoxia. The present study tested the hypothesis that reactive
      oxygen species (ROS) released from mitochondria regulate the cytosolic redox
      state and are required for the stabilization of p53 protein levels in response to
      hypoxia. Our results indicate that hypoxia (1.5% O2) increases mitochondrial ROS
      generation and increases p53 protein levels in human breast carcinoma MCF-7 cells
      and in normal human diploid fibroblast IMR-90 cells. MCF-7 cells depleted of
      their mitochondrial DNA (rho(o) cells) failed to stabilize p53 protein levels
      during hypoxia. The antioxidant N-acetylcysteine and the Cu/Zn superoxide
      dismutase inhibitor diethyldithiocarbamic acid abolished the hypoxia-induced
      increases in ROS and p53 levels. Rotenone, an inhibitor of mitochondrial complex
      I, and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, a mitochondrial anion
      channel inhibitor, also abolished the increase in ROS signal and p53 levels
      during hypoxia. The p53-dependent gene p21WAF1/CIP1 was also induced by hypoxia
      in both MCF-7 and IMR-90 cells without affecting the growth rate of either cell
      line. In contrast, both cell lines exhibited increases in p21WAF1/CIP1 expression
      and growth arrest after gamma irradiation. Primary chick cardiac myocytes and
      murine embryonic fibroblasts also showed an increase in p53 protein levels in
      response to hypoxia without cell death or growth arrest. These results indicate
      that mitochondria regulate p53 protein levels during hypoxia through a redox
      dependent mechanism involving ROS. Despite p53-induction, hypoxia alone does not
      cause either growth arrest or cell death.

PMID- 10951579
TI  - F9 embryonal carcinoma cells fail to stop at G1/S boundary of the cell cycle
      after gamma-irradiation due to p21WAF1/CIP1 degradation.
AB  - We studied the ability of F9 teratocarcinoma cells to arrest in G1/S and G2/M
      checkpoints after gamma-irradiation. Wild-type p53 protein was rapidly
      accumulated in F9 cells after gamma-irradiation, however, this was followed not
      by a G1/S arrest but by a short and reversible delay of the cell cycle in G2/M.
      In order to elucidate the reasons of the lack of G1/S arrest in F9 cells, we
      investigated the expression of p53 downstream target Cdk inhibitor p21WAF1/CIP1.
      In spite of p53-dependent activation of p21WAF1/CIP1 gene promoter and
      p21WAF1/CIP1 mRNA accumulation upon irradiation, the p21WAF1/CIP1 protein was not
      detected by either immunoblot or immunofluorescence techniques. However, the
      cells treated with a specific proteasome inhibitor lactacystin revealed the
      p21WAF1/CIP1 protein both in non-irradiated and irradiated cells. Therefore we
      suggest that p21WAF1/CIP1 protein is degraded by a proteasome-dependent mechanism
      in F9 cells and the lack of G1/S arrest after gamma-irradiation is due to this
      degradation. We also examined the expression and activity of cell cycle
      regulatory proteins: G1- and G2-cyclins and cyclin-dependent kinases. In the
      absence of functional p21WAF1/CIP1 inhibitor, the activity of G1 cyclin/Cdk
      complexes was insufficiently inhibited to cause a G1 arrest, whereas a decrease
      of cdc2 and cyclin B1-associated kinase activities was enough to contribute to a
      reversible G2 arrest following gamma-irradiation. After gamma-irradiation, the
      majority of F9 cells undergo apoptosis implying that wt-p53 likely triggers pro
      apoptotic gene expression in DNA damaged cells. Elimination of defected cells
      might ensure maintenance of genome integrity in the remaining cell population.

PMID- 10951581
TI  - pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at
      physiologically relevant levels.
AB  - A key difference among the three structurally similar pRB family members is that
      only pRB is a tumor suppressor. Identification of distinctive functional
      differences between pRB and p107/p130 therefore holds promise for a better
      understanding of the tumor suppression mechanisms of pRB. Enigmatically, pRB and
      p107 have been shown to have indistinguishable growth suppression activities when
      studied in the pRB-deficient Saos-2 cell system. In this study, we discovered
      that, when expressed at physiologically relevant levels, pRB and p107 had
      distinctive effects in causing growth suppression. pRB induced cellular p130
      levels while p107 repressed them. p107, but not pRB, blocked cells inside S phase
      in addition to G1 arrest. In contrast, no qualitative differences were identified
      in their abilities to repress the expression of a set of suspected pRB/E2F
      repression target genes. These results indicate that pRB and p107 possess
      different growth suppression effects, despite the fact that they have similar E2F
      repression effects.

PMID- 10951580
TI  - G2A is an oncogenic G protein-coupled receptor.
AB  - G2A is a heptahelical cell surface protein that has recently been described as a
      potential tumor suppressor, based on its ability to counteract transformation of
      pre-B cells and fibroblasts by Bcr-Abl, an oncogenic tyrosine kinase. We have
      isolated cDNAs encoding G2A in the course of screening libraries for clones that
      cause oncogenic transformation of NIH3T3 fibroblasts. When expressed at high
      levels in NIH3T3 cells by retroviral transduction, G2A induced a full range of
      phenotypes characteristic of oncogenic transformation, including loss of contact
      inhibition, anchorage-independent survival and proliferation, reduced dependence
      on serum, and tumorigenicity in mice. When expressed by transfection, G2A greatly
      enhanced the ability of a weakly oncogenic form of Raf-1 to transform NIH3T3
      cells. These results demonstrate that G2A is potently oncogenic both on its own
      and in cooperation with another oncogene. Expression of G2A in fibroblasts and
      endothelial cells resulted in changes in cell morphology and cytoskeleton
      structure that were equivalent to those induced by the G protein subunit
      Galpha13. Transformation of NIH3T3 cells via G2A expression was completely
      suppressed by co-expression of LscRGS, a GTPase activating protein that
      suppresses signaling by Galpha12 and Galpha13. Hyperactivity of Galpha12 or
      Galpha13 has previously been shown to result in activation of Rho GTPases. G2A
      expression resulted in activation of Rho, and transformation via G2A was
      suppressed by a dominant negative form of RhoA. These results indicate that G2A
      may be directly coupled to Galpha13, and that it is the activation of this Rho
      activating Galpha protein which is responsible for the ability of G2A to
      transform fibroblasts.

PMID- 10951582
TI  - Immuno-histochemical detection of human telomerase reverse transcriptase in human
      liver tissues.
AB  - Although telomerase activity in hepatocellular carcinoma (HCC) increases in
      accordance with degree of histological undifferentiation, it is unknown whether
      the level of telomerase activity in HCC reflects of the degree of activity in
      individual cells or the frequency of telomerase-positive HCC cells. Non-cancerous
      liver tissues exhibit low but significant levels of telomerase activity, but the
      nature of telomerase-positive cells in these tissues is unclear. In this study,
      we performed immunohistochemical staining using specific antibody against
      telomerase reverse transcriptase (hTERT) protein in 15 HCC samples and 13
      adjacent non-cancerous liver tissues. There were hTERT-positive hepatocytes,
      though very low frequency, in non-cancerous liver tissues. The frequencies in
      hTERT positive hepatocytes were very well correlated with clinicopathological
      parameters and telomerase activity levels: the average frequencies of chronic
      hepatitis was 0.2%, liver cirrhosis 0.2%, well-differentiated HCC 3.0%,
      moderately differentiated HCC 28%, and poorly differentiated HCC 95%. The
      intensity of staining varied among cells within a given specimen, and correlation
      with degree of histological undifferentiation was less obvious. Portions of
      migrating lymphocytes and biliary epithelial cells were also hTERT-positive.
      These findings indicate that the upregulation of telomerase activity with degree
      of undifferentiation of HCC is mainly due to the increase in frequency of hTERT
      positive HCC cells.

PMID- 10951583
TI  - The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine
      phosphatase PTP-BL via an alternatively spliced PDZ domain.
AB  - Mutations of the tumor suppressor protein APC (Adenomatous Polyposis Coli) are
      linked to familiar and sporadic human colon cancer. Here we describe a novel
      interaction between the APC protein and the protein tyrosine phosphatase PTP-BL
      carrying five PDZ protein-protein interaction domains. Exclusively, the second
      PDZ domain (PDZ2) of PTP-BL is binding to the extreme C-terminus of the APC
      protein, as determined by yeast two-hybrid studies. Using surface plasmon
      resonance analysis we established a dissociation constant (K(D)) of 8.1 x 10(-9)
      M. We find that a naturally occurring splice insertion of five amino acids
      (PDZ2b) abolishes its binding affinity to the APC protein. The in vivo
      interaction between PTP-BL and the APC protein was shown by coprecipitation
      experiments in transfected COS cells. Furthermore, in cultured epithelial Madine
      Carnine Kidney cells the subcellular colocalization was demonstrated for the
      nucleus and also for the tips of cellular extensions. The interaction of the APC
      protein with a protein tyrosine phosphatase may indirectly modulate the steady
      state levels of tyrosine phosphorylations of associated proteins, such as beta
      catenin playing a major role in the regulation of cell division, migration and
      cell adhesion.

PMID- 10951584
TI  - Notch(ic)-ER chimeras display hormone-dependent transformation, nuclear
      accumulation, phosphorylation and CBF1 activation.
AB  - Notch genes encode a family of evolutionarily conserved transmembrane receptors
      that are involved in many distinct cellular processes such as differentiation,
      proliferation and apoptosis. Notch function has been shown to be required both
      during development and in adult life. Moreover, several studies on spontaneous
      human tumors and in experimental models demonstrate that three of the four
      mammalian Notch genes can act as oncogenes. The mechanism by which Notch proteins
      induce neoplastic transformation is not known. In order to determine the early
      signaling events mediated by Notch during cellular transformation we constructed
      several inducible alleles of Notch(ic) by fusing portions of Nic to the hormone
      binding domain of the estrogen receptor. Here we show that Notch(ic)-ER chimeras
      are conditionally activated by 4-Hydroxytamoxifen (OHT) in a dose-dependent
      manner. Clonal RKE cell lines expressing Notch(ic)-ER chimeras display hormone
      dependent transformation in vitro. Transformation mediated by Notch(ic)-ER is
      reversible and chronic stimulation is necessary for the maintenance of the
      transformed phenotype. In response to hormone activation Notch(ic)-ER chimeras
      become hyperphosphorylated and accumulate in the nucleus of the cell; indicating
      that both phosphorylation and nuclear localization are required for Notch
      transforming activity.

PMID- 10951585
TI  - The Src/Csk regulatory circuit arose early in metazoan evolution.
AB  - We have identified a gene encoding a member of the Csk family of non-receptor
      protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ
      hybridization analysis of the distribution of RNA from the Hydra Csk gene
      indicates that it is expressed in most of the epithelial cells of the adult polyp
      and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with
      that of STK, the Hydra Src gene orthologue, reveals that the two genes are
      largely co-expressed. Such co-expression is consistent with a role for Hydra Csk
      in regulation of STK activity. This possibility was tested directly by
      coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth
      inhibition seen when STK alone is expressed in yeast. Suppression was dependent
      on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail
      of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk
      resulted in suppression of STK kinase activity. Taken together these data
      indicate that the regulatory circuit involving Src and Csk PTKs was established
      prior to the divergence of the phylum Cnidaria from the rest of the metazoans.

PMID- 10951586
TI  - Isolation and characterization of the human A-myb promoter: regulation by NF-Y
      and Sp1.
AB  - The A-myb transcription factor shows a restricted tissue distribution and is cell
      cycle regulated. Furthermore its deregulation has profound effects on the growth
      and/or differentiation of the cells in which it is normally expressed. We have
      therefore characterized its promoter. A 12 kb genomic clone was isolated that
      comprises the first exon, part of the first intron as well as upstream regulatory
      sequences. Multiple transcription start sites have been identified which operate
      in both B lymphocytes and epithelial cells and the upsteam region was shown to
      have promoter, activity. The boundaries of the minimal promoter region (-183-14),
      of a positive upstream (-538-183) and a negative downstream regulatory region
      (NRE) (+83+374) have been defined. The NRE is promoter- and orientation
      independent but position specific. The A-myb minimal promoter is GC-rich, does
      not contain any TATA box but has a functional CCAAT box. The CCAAT box and
      minimal promoter is highly conserved in the corresponding murine sequence. The
      CCAAT box efficiently binds the NF-Y complex and its mutation decreases basal
      promoter activity by 50%. Two Sp1 binding sites are present upstream from the
      CCAAT box which can bind Spl and contribute to A-myb promoter activity by 70 and
      30%, respectively. The two Sp1 sites and CCAAT box together contribute to over
      80% of A-myb basal promoter activity and are therefore the major regulatory
      elements. Finally, we show that the promoter is cell cycle regulated and that the
      SP1 and CCAAT elements are required for S phase induction.

PMID- 10951587
TI  - Requirement for caspase activation in monocytic differentiation of myeloid
      leukemia cells.
AB  - Human myeloid leukemia cells respond to 12-tetradecanoylphorbol-13-acetate (TPA)
      and other activators of protein kinase C (PKC) with the induction of terminal
      monocytic differentiation. The present studies demonstrate that TPA treatment of
      U-937 leukemia cells is associated with release of mitochondrial cytochrome c,
      activation of caspase-3 and induction of internucleosomal DNA fragmentation. By
      contrast, the TUR cell variant, which is deficient in PKCbeta, failed to respond
      to TPA with release of cytochrome c and induction of the caspase-3 cascade.
      Moreover, stable overexpression of PKCbeta in TUR cells reconstituted sensitivity
      to TPA-induced cytochrome c release and activation of caspase-3. The results also
      demonstrate that treatment of cells with the caspase inhibitor Z-VAD-fmk blocks
      both TPA-induced apoptosis and monocytic differentiation. Similar results were
      obtained in U-937 cells stably expressing the CrmA caspase inhibitor. These
      findings demonstrate that TPA induces cytochrome c release by a PKCbeta-dependent
      mechanism and that activation of caspase-mediated signaling is required for
      induction of the differentiated monocytic phenotype.

PMID- 10951588
TI  - The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK
      pathway.
AB  - Activating mutations of RAS are thought to be early events in the evolution of
      thyroid follicular neoplasms. We used a doxycycline-inducible expression system
      to explore the acute effects of H-RAS12 on genomic stability in thyroid PCCL3
      cells. At 2-3 days (first or second cell cycle) there was a significant increase
      in the frequency of micronucleation. Treatment of cells with YVAD-CHO inhibited
      RAS-induced apoptosis, but had no effect on micronucleation. The effects of H
      RAS(V12) were mediated by activation of MAPK, as treatment with PD98059 at
      concentrations verified to selectively inhibit MEK1 reduced the frequency of
      prevalence of cells with micronuclei. In addition, doxycycline-inducible
      expression of a constitutively active MEK1, but not of a mutant RAC1, mimicked
      the effects of H-RAS(V12). The effects of H-RAS(V12) on genome destabilization
      were apparent even though the sequence of p53 in PCCL3 cells was confirmed to be
      wild-type. Acute activation of H-RAS(V12) evoked a proportional increase in both
      CREST negative and CREST positive micronuclei, indicating that both clastogenic
      and aneugenic effects were involved. H-RAS(V12) and activated MEK1 also induced
      centrosome amplification, and chromosome misalignment. Evidence that acute
      expression of constitutively activated RAS destabilizes the genome of PCCL3 cells
      is consistent with a mode of tumor initiation in which this oncogene promotes
      phenotypic progression by predisposing to large scale genomic abnormalities.

PMID- 10951589
TI  - Bcl-w is an important determinant of damage-induced apoptosis in epithelia of
      small and large intestine.
AB  - The potential role of the bcl-2 relative bcl-w as a physiological regulator of
      apoptosis in intestinal epithelia has been investigated. Immunoblots for bcl-w
      with new monoclonal antibodies revealed that it was expressed in the small
      intestine and colon, among other murine tissues, as well as in six human tumour
      cell lines of epithelial origin, including two colon carcinoma lines. To assess
      whether bcl-w regulates either spontaneous or damage-induced apoptosis in the
      small intestine or colon, apoptosis in intestinal crypts of bcl-w -/- and wild
      type mice was quantified microscopically on a cell positional basis. Spontaneous
      apoptosis within crypt epithelia was not significantly increased by loss of bcl
      w, in either the small intestine or midcolon. However, after treatment with the
      cytotoxic drug 5-fluorouracil or with gamma-radiation, the bcl-w-null animals
      exhibited substantially more apoptosis than their wild-type counterparts in both
      tissues. The greatest enhancement of apoptosis attributable to the absence of bcl
      w (up to sixfold) occurred in the small intestine. Hence, bcl-w is an important
      determinant of damage-induced apoptosis in intestinal epithelia, and unlike bcl
      2, which regulates only colonic apoptosis, plays a major role in small intestinal
      epithelium.

PMID- 10951590
TI  - Instituto Oswaldo Cruz: first centenary (1900-2000)

PMID- 10951591
TI  - Schistosomiasis information systems and control of snail-borne diseases.

PMID- 10951592
TI  - Praziquantel and the control of schistosomiasis.

PMID- 10951593
TI  - Malaria: a new gene family (clag) involved in adhesion.

PMID- 10951594
TI  - A mitochondrion in Entamoeba histolytica?

PMID- 10951595
TI  - US sandflies and leishmaniasis on the Web

PMID- 10951596
TI  - The nematode polyprotein allergens/antigens.
AB  - Interest in the nematode polyprotein allergens/antigens (NPAs) originally arose
      because they were often found to be immunodominant antigens of nematode
      parasites, and in some cases also potent allergens. Quite separately, they
      attracted attention as the 'ladder' proteins found close to the surface of
      filarial nematodes. Screening of cDNA expression libraries with antibody from
      infected humans or domestic animals continues to reveal more NPAs. The search for
      the biochemical function(s) of NPAs was originally hampered by the lack of amino
      acid sequence similarities between NPAs and proteins of known function, but much
      is now known about their biochemical activity, the highly unusual means of their
      biosynthesis and their gene structure. Here, Malcolm Kennedy provides an update
      on these intriguing proteins.

PMID- 10951597
TI  - The development of Trypanosoma cruzi in triatominae.
AB  - Trypanosoma cruzi multiplies and differentiates in the digestive tract of
      triatomine insects. These insects ingest an enormous amount of blood, with
      ingestion followed very rapidly by a strong diuresis, slow digestion and
      occasionally long periods of starvation. Resulting changes in the intestinal
      environment induce the development of dominant stages of T. cruzi--epimastigotes
      and metacyclic trypomastigotes--and can be correlated with the appearance of
      specific developmental stages--spheromastigotes and giant cells--which otherwise
      are only rarely seen. Here, Astrid Kollien and Gunter Schaub outline recent
      research on these developmental steps of T. cruzi in the vector, and the effects
      of different compounds acting against the parasite in the vector.

PMID- 10951598
TI  - Litomosoides sigmodontis in mice: reappraisal of an old model for filarial
      research.
AB  - Onchocerciasis and lymphatic filariasis (LF) are major causes of severe morbidity
      and considerable socio-economic problems throughout the tropics. Vector control
      and mass chemotherapy have helped to control these infections in some regions,
      but the temporary success of such measures argues strongly for the development of
      vaccines. Success in such a venture will require detailed knowledge of protective
      immune responses in conjunction with the identification of target antigens. By
      comparison with other important parasitic infections, such as schistosomiasis and
      leishmaniasis, work on the development of vaccines for onchocerciasis and LF has
      been constrained because of the difficulties of producing cyclical and patent
      filarial infection in laboratory mice. Wolfgang Hoffmann and colleagues here
      outline the opportunities presented by the rodent filaria Litomosoides
      sigmodontis for filarial research.

PMID- 10951599
TI  - The origin of antigenic diversity in Plasmodium falciparum.
AB  - Most studies of genetic variability of Plasmodium falciparum have focused on
      protein antigens and the genes that encode them. The consensus is that
      populations exhibit high levels of genetic polymorphism, most notably the genes
      encoding surface proteins of the merozoite (Msp1, Msp2) and the sporozoite (Csp).
      The age and derivation of this variation is a subject that warrants further
      careful consideration, as discussed here by Stephen Rich, Marcelo Ferreira and
      Francisco Ayala.

PMID- 10951600
TI  - Natural versus drug-induced resistance in Schistosoma mansoni infection.
AB  - Rodrigo Correa-Oliveira, Iramaya Rodrigues Caldas and Giovanni Gazzinelli here
      focus on the immune response of individuals with natural resistance to
      schistosomiasis, which differs significantly from that of post-treatment
      resistant and infected individuals. They suggest that the activation of T helper
      type 1 (Th1) and Th2 cells is needed for the induction of natural resistance
      against Schistosoma mansoni infection.

PMID- 10951602
TI  - 'Transfection' vs 'transformation': defining terms.

PMID- 10951601
TI  - Parasite proteomics.
AB  - Proteomics offers a new set of tools for investigating parasites and parasite
      associated disease. In this article, John Barrett, Jim Jefferies and Peter Brophy
      describe the key technologies involved, including two-dimensional gel
      electrophoresis, image analysis, biological mass spectroscopy and database
      searching. The potential applications of proteomics in drug and vaccine discovery
      are reviewed, as are possible future developments.

PMID- 10951604
TI  - Reply

PMID- 10951603
TI  - More on the ecological impact of fungal infections on wildlife populations.

PMID- 10951605
TI  - Malaria: A new gene family (clag) involved in adhesion - reply

PMID- 10951606
TI  - The Kleine-Levin syndrome. Report of a case and review of the literature.
AB  - Kleine-Levin syndrome is a rare self-limited disorder which usually affects
      adolescent males and is characterized by episodic hypersomnia, increased
      appetite, and behavioral/psychiatric disturbances. Individuals are normal between
      the attacks. The case of an adolescent boy is presented who suffered from
      recurrent sleepiness, hyperphagia, and behavioral disturbances such as rocking,
      punching and pacing, and was originally misdiagnosed as suffering from
      encephalitis. Before the diagnosis of Kleine-Levin was given, the patient
      underwent unnecessary investigations and treatment which, in turn, complicated
      his clinical condition both physically as well as psychologically. In the course
      of five years he had four such episodes which appeared to have progressively
      milder manifestations. Between episodes he was normal. It is important that the
      diagnosis is suspected early, especially in adolescent males who present with
      recurrent episodes of somnolence, increased appetite, and abnormal behavior,
      since it most often represents a benign and self-limited entity and does not
      warrant extensive investigations or treatment. It is also important to
      distinguish this syndrome from more serious organic and psychiatric diseases with
      more serious prognoses. The differential diagnosis of this syndrome is discussed
      and a review of the literature is presented including evidence and hypotheses
      regarding its pathophysiology.

PMID- 10951607
TI  - Neuropsychological function in subjects with psychotic and affective disorders.
      Relationship to diagnostic category and duration of illness.
AB  - OBJECTIVE: To explore the links between neuropsychological performance,
      diagnostic category and duration of illness in subjects with psychotic and
      affective disorders. METHODS: Memory and executive abilities were tested in
      consecutively admitted patients with schizophrenia (N = 20), other non
      schizophrenic psychotic disorders (N = 29), bipolar disorder (N = 33) and major
      depression (N = 19). RESULTS: Subjects with schizophrenia had poorer global
      memory performances than subjects with major depression, and poorer delayed
      verbal memory abilities than those from the other three diagnostic groups.
      Executive abilities explored by the Stroop test and the Wisconsin Card Sorting
      Test did not differ between diagnostic groups. Neuropsychological performances
      were not influenced by previous duration of illness. CONCLUSION: Memory deficits
      are the most discriminatory cognitive features between subjects with
      schizophrenia and those with other psychotic or mood disorders. The fact that
      cognitive deficits are static whatever the diagnostic group indirectly suggests
      that they may have a neurodevelopmental origin in subjects with schizophrenia,
      but perhaps also in subjects with other psychotic and mood disorders.

PMID- 10951608
TI  - The intellectual development, mental and behavioural disorders in children from
      Belarus exposed in utero following the chernobyl accident.
AB  - The study examined psychological development in 250 children at the age of 6-7
      and 10-12 years who had been exposed in the prenatal period at the time of the
      Chernobyl accident in 1986. These children were compared to a control group of
      250 children of the same age from non- and slightly contaminated areas of
      Belarus. The examination included psychiatric examination and intellectual
      assessment as well as the estimation of thyroid exposure in utero. The mean value
      of thyroid doses from (131)I 0.39 Gy was estimated for the prenatal exposed
      children. The children of the exposed group had a lower mean full-scale IQ
      compared to the control group (89.6 +/- 10.2 vs 92.1 +/- 10.5 at the age of 6-7
      years, P = 0.007; and 94. 3 +/- 10.4 vs 95.8 +/- 10.9 at the age of 10-12 years,
      P = 0.117). Average IQ for the subgroup of highly exposed children (thyroid doses
      more than 1 Gy) was lower in comparison with average IQ for the whole exposed
      group (85.7 +/- 6.4 vs 89.6 +/- 10.2 at the age of 6-7 years, P = 0.014; 89.1 +/-
      7.1 vs 94.3 +/- 10.4 at age 10-12 years, P = 0.003). No statistically significant
      distinctions in average IQ were found between the different subgroups of children
      in relation to the gestational age at the time of the Chernobyl accident. We
      notice a positive moderate correlation between IQ of children and the educational
      level of their parents (in exposed group - mothers: r = 0.50, P < 0.01 and
      fathers: r = 0.52, P < 0.01; in control group - mothers: r = 0.41, P < 0.05 and
      fathers: r = 0.42, P < 0.05). There was a moderate correlation between high
      personal anxiety in parents and emotional disorders in children (for mothers r =
      0.38, P < 0.05; for fathers r = 0.43, P < 0.01). The relative risk of mental and
      behavioural disorders has been estimated for emotional disorders OR = 2.67, P <
      0.001. The frequency of the formation of mental retardation, hyperkinetic
      disorders and other mental and behavioural disorders in children from both groups
      was approximately the same. We conclude that in the genesis of borderline
      intellectual functioning and emotional disorders in the exposed group of children
      a significant role was probably played by unfavourable social-psychological and
      sociocultural factors such as a low educational level of the parents, the break
      of microsocial contacts and difficulties adapting, which appeared following the
      evacuation and relocation from the contaminated areas.

PMID- 10951609
TI  - Visuo-spatial attention processes in panic disorder with agoraphobia: a pilot
      study using a visual target discrimination task.
AB  - Panic attacks can be observed in a wide range of situations, but most common are
      those providing complex and unstructured stimulations, suggesting an impairment
      in attentional processing of visuo-spatial information. This study evaluated
      agoraphobics' attentional processing of neutral (i.e., not anxiety-provoking)
      visuo-spatial stimulation. Twelve patients suffering from panic attacks with
      agoraphobia were compared with 22 normal controls on a computerized visual target
      discrimination task specifically designed for this study. Psychometric measures
      assessed the phobic avoidance, the level of depression and anxiety. The numbers
      of errors and reaction times were analysed with a three-way ANOVA (Group x target
      modality x number of stimulations). No between-group significant difference was
      found for the reaction time performance and the mean number of detection errors.
      However, an interaction effect was observed for this last variable depending on
      the target modality: agoraphobic patients made fewer omission errors than control
      subjects when the target was present among distractors, while they made more
      commission errors when the target was absent. Outcomes are discussed in terms of
      attentional hyperactivation related to anxiety and perseverative decision process
      in agoraphobic patients.

PMID- 10951610
TI  - An enquiry into recurrent brief depressive episodes in the general population.
AB  - Spontaneous remarks to the author concerning the experience of brief depressive
      episodes prompted an enquiry into the experience of these in the general
      population. The finding that a high proportion of subjects admitting to the
      experience of recurring brief depression, that the episodes were generally of
      less than 24 hours' duration, suggests that allowance should be made for such
      very brief episodes in future enquiry of the topic, as these would not be
      recognised by the criteria for recurrent brief depression in the ICD and DSM
      definitions. There was no association of duration of episode with either age or
      gender. There did not appear to be an association of episode duration with
      possible precipitants of stress, climatic conditions, season of year or dietary
      factors.

PMID- 10951611
TI  - Duration of untreated psychosis and the long-term course of schizophrenia.
AB  - This study examines the relationship between duration of untreated psychosis
      (DUP) and long-term symptomatic and social outcome in 205 patients with
      schizophrenia, whose parents are member of a consumer organisation. We found only
      a tendency that longer DUP was related to negative symptoms, but no relation to
      other outcome domains. The results of this study do not support antipsychotic
      intervention at the earliest sign of psychosis in order to 'protect the brain'.

PMID- 10951612
TI  - Does placebo help establish equivalence in trials of new antidepressants?
AB  - Clinical trials of new antidepressants usually compare a new drug to a reference
      antidepressant and to a placebo. The placebo is intended to validate the trial in
      the case of a no-difference outcome, i.e., it helps in assessing equivalence. The
      aim of the present paper is to test whether placebo has indeed helped establish
      equivalence of effect in comparative trials of new antidepressants. We carried
      out an example of sample size determination first in a trial to show a difference
      between the new and control drug, and second in a trial to assess equivalence
      between two competing drugs. Finally, we retrospectively calculated the maximum
      difference accepted as equivalence of effect in published trials of new
      antidepressants. Assuming a response rate to antidepressants of 70%, 294 subjects
      for each treatment group are needed to show a 10% difference between two
      antidepressant drugs and more than 1,300 to assess equivalence at a 5% level of
      delta, the maximum difference acceptable as equivalence of effect. The level of
      delta in published trials of new antidepressants ranges between 12 and 43%,
      suggesting they cannot claim to demonstrate equivalence of effect. Therefore, the
      presence of a placebo arm for comparison didn't help establish whether both drugs
      really worked the same way. Comparative trials of new antidepressants should
      adopt a two-arm design, a suitable number of patients and a high standard in the
      experimental design in order to minimise possible control-event rate variation.

PMID- 10951613
TI  - Comparison of four scales measuring depression in schizophrenic inpatients.
AB  - Several scales have been used to diagnose and evaluate depression in
      schizophrenia. However, the association between different depression scales and
      between depression scales and negative symptoms has not been studied adequately.
      Sixty-four consecutively admitted schizophrenic patients to Eginition Hospital,
      Department of Psychiatry, Athens, were assessed on the following scales: the
      Calgary Depression Scale for Schizophrenia (CDSS), the Hamilton Depression Rating
      Scale (HDRS), the Expanded Brief Psychiatric Rating Scale-Depression subscale
      (EBPRS-D), the Positive and Negative Syndrome Scale-Depression subscale (PANSS-D)
      and the Negative Symptoms subscale (PANSS-N). The depression scales were found to
      be highly intercorrelated with the exception of the comparison between the EBPRS
      D and the PANSS-D. Out of the four depression scales studied, only CDSS and EBPRS
      D can discriminate between depression and a PANSS-Negative Symptoms subscale
      score or negative item scores.

PMID- 10951614
TI  - The composite scale of morningness: further psychometric properties and temporal
      stability.
AB  - OBJECT: To assess the temporal stability of the French version of the Composite
      Scale of Morningness (CSM), and to replicate our previous findings in an
      independent sample in order to confirm the good internal properties of this
      instrument. METHOD: Sixty nursing students (11 males and 49 females) filled out
      the Composite Scale of Morningness on two occasions over a 13-month period.
      RESULTS: The scale's reliability is high: Cronbach's alpha = 0.874 in males and
      0.904 in females. The CSM total scores are normally distributed and independent
      of gender. They do not differ between occasions, and are highly correlated: r =
      +0.885 in males and r = +0.930 in females. CONCLUSION: The French version of the
      CSM is stable over time and psychometrically reliable. These are the
      characteristics of a personality trait. Further studies should explore its
      personality, biological and genetic correlates.

PMID- 10951615
TI  - Case report: eating disorder following torture.

PMID- 10951616
TI  - [Effects of heparin on the growth, extracellular matrix and matrix
      metalloproteinase gene expression in rat hepatic stellate cells].
AB  - OBJECTIVE: To study the effects of heparin on the growth, extracellular matrix
      and matrix metalloproteinase (MMP) gene expression in rat hepatic stellate cells
      (HSC). METHODS: Activated HSC was treated by heparin or fetal calf serum without
      heparin. The cell growth was evaluated by actual cell count and BrdU-labelled
      immunocytochemical stain. The gene expressions of type I and IV procollagen,
      fibronectin, MMP-2 and membrane type matrix metalloproteinase (MT-MMP) were
      investigated by immunocytochemical stain and digoxigenin-labeled in situ
      hybridization technique, respectively. In addition, the gelatinase activity of
      MMP-2 was examined by zymography. RESULTS: Heparin could obviously reduce HSC
      growth, inhibit the synthesis of type I procollagen and fibronectin protein, and
      the gene expressions of type I procollagen, fibronectin and MT-MMP. The
      expressions of type IV procollagen, MMP-2 and MMP-2 activity were not affected by
      heparin. CONCLUSION: The results demonstrate that heparin can inhibit HSC
      proliferation, down-regulate interstitial collagen synthesis and inhibit MT-MMP
      gene expression.

PMID- 10951617
TI  - [The relationship between the levels of serum fibrosis marks and morphometric
      quantitative measurement of hepatic histological fibrosis].
AB  - OBJECTIVE: To study the relationship between the levels of serum fibrosis marks
      hyaluronic acid (HA), procollagen type III (PCIII), collagen type IV (CIV) and
      the degree of hepatic fibrosis, and the clinical significance of HA, PCIII, CIV
      in the diagnosis of hepatic fibrosis to the chronic viral hepatitis. METHODS: The
      concentrations of serum HA, PCIII, CIV in 151 patients with chronic viral
      hepatitis were measured by radioimmunoassay. Liver biopsies were performed in all
      of the patients at the same time. Morphometric quantitative measurements of
      hepatic fibrosis were performed in 4mum sections stained with masson stain using
      a fully automated image-analysis system. RESULTS: The levels of serum HA, PCIII,
      CIV were all increased steadily with the progression of hepatic fibrosis, and the
      highest levels were in stage 4. They were all positively correlated with staging
      of the liver pathology and morphometric measurement of hepatic fibrosis
      (P<0.001). The coefficient value (r) with staging were 0.694, 0.493, 0.552
      (P<0.001), respectively and with morphometric measurement of hepatic fibrosis
      were 0.715, 0.596, 0.537 (P<0.001), respectively. CONCLUSION: The levels of serum
      HA, PCIII, CIV are in concert with the degree of hepatic fibrosis, and the
      determination of these marks may be valuable for diagnosing hepatic fibrosis.

PMID- 10951618
TI  - [Disorders of hepatic sinusoids and perisinusoidal space in chronic viral
      hepatitis B and its relationship to hepatic fibrosis].
AB  - OBJECTIVE: To explore the disorders of the hepatic sinusoids and perisinusoidal
      space in chronic viral hepatitis B and its relationship to hepatic fibrosis.
      METHODS: The histopathology, the expression of smooth muscle actin (SMA),
      fibronectin (FN), laminin (LN) and collagen type IV (C-IV), and deposition of
      reticular, collagenous and elastic fibers in the sinusoids and perisinusoidal
      space in 160 liver biopsy specimens of viral hepatitis B were examined by
      haematoxyln and eosin (HE), immunohistochemistry and special stains techniques,
      respectively. RESULTS: The pathological changes of the hepatic sinusoids were
      collapsing, expansive, occlusive and narrowing. The changes in SMA distribution
      were characteristic. The spotty activated stellate cells were proliferating,
      transiting, expressing SMA, and stretching down the wall of sinus or forming fine
      bundles in G(1) or G(2); they were more active in proliferation, transition,
      forming bridging and even wide fibrous septa constituted by myofibroblast cells
      in G(3) or G(4). The other 3 elements, FN, IV-C, LN and reticular, collagenous
      and elastic fibers deposited in the sinusoids and perisinusoidal space following
      SMA. The higher the gradings were, the more the depositing elements were. They
      mainly deposited in the areas of degeneration, inflammation, necroses and fibrous
      bundles (septa) where the pathologic changes of sinusoids happened. CONCLUSION:
      The sinusoids and perisinusoidal space is the original sites of fibrosis. Special
      attention should be paid to the pathological changes in the sinusoids and
      perisinusoidal space when to evaluate the gradings of histopathology and stagings
      of hepatic fibrosis.

PMID- 10951619
TI  - [Expression and plasma activity of plasminogen activator inhibitor-1 infibrotic
      liver tissues].
AB  - OBJECTIVE: To study plasminogen activator inhibitor-1 (PAI-1) gene expression and
      protein synthesis in fibrotic liver tissues and plasma activity levels. METHODS:
      Plasma PAI-1 activity was detected by chromogenic activity assay kit. The
      messenger RNA (mRNA) of PAI-1 and PAI-1 protein was detected on serial biopsied
      liver specimens of normal, HBV-related chronic hepatitis and cirrhosis by in situ
      hybridization and immunohistochemistry. The semi-quantitative results of the
      protein expression to immunohistochemistry staining were analysed in contrast
      with the stage of hepatic fibrosis. RESULTS: The plasma PAI-1 activity levels
      decreased with the progression of hepatic fibrosis. PAI-1 mRNA and protein were
      expressed in the extracellular matria deposition of the portal areas, focal
      necrotic areas, fibrous septa and hepatocytes as well as the hepatocellular
      cytoplasm adjacent to the areas described above. CONCLUSION: Localization of PAI
      1 is not only in interstitial cells but also hepatocytes, suggesting an intense
      relationship between PAI-1 and hepatic fibrosis.

PMID- 10951620
TI  - [Effects of hepatitis B virus X gene on apoptosis and the activity of telomerase
      in HepG(2) cells].
AB  - OBJECTIVE: To observe the effects of hepatitis B virus X gene on hepatic
      carcinoma. METHODS: The expression vectors of HBs gene and HBc gene (pCEP4-S and
      pCEP4-C) were transfected into HepG(2) cells by electroporation technique, and
      the cells, HepG(2) cells which contained the expression vectors of HBs (pCEP4-X)
      were recovered and cultured stably. The activity index of telomerase and the
      apoptosis rates in three cell lines were determined by PCR-ELISA and flow
      cytometry. RESULTS: The 39.50% of cells expressed HBx gene came into S-phase of
      cell cycle, and the activity index of telomerase was higher in the cell line
      (3.95 +/- 0.07) than in other cell lines and control (F=20.85, P<0.01; d'=2.15,
      P<0.05) after synchronized culture. Induced by antisense oligonucleotides against
      telomerase the apoptosis of cell line expressed HBx gene reduced (apoptosis rate:
      1.75%). The activity of cells also reduced with the dose increase of the
      antisense oligonucleotides and it showed a dose-response relationship.
      CONCLUSION: The activity of HepG(2) cell can be increased and the cell apoptosis
      can be reduced by HBx gene. It may be another malignant process of hepatocytes.

PMID- 10951621
TI  - [Resistance of Bcl-2 adenovirus vector to HepG(2) cell apoptosis induced by
      ethanol].
AB  - OBJECTIVE: To evaluate the role of Bcl-2 family proteins in hepatocytic apoptosis
      caused by ethanol. METHODS: We induced hepatocytic apoptosis in HepG(2) cells
      with ethanol and detected the apoptosis with TUNEL assay. Bcl-2, Bax, and Bak
      protein expression in the hepatocytes was determined by immunohistochemistry
      method. We also observed the expression of Bcl-2 protein in HepG(2) cells
      infected with Bcl-2 adenovirus vector and its protection against hepatocytic
      apoptosis caused by ethanol. RESULTS: No obvious cytotoxicity was noted in 0.2%
      and 1% ethanol treatment group, while it developed in 3% ethanol treatment group
      and accompanied by a marked expression of Bax, Bak proteins. CONCLUSION: The
      overexpression of Bax, Bak proteins may play a role in HepG(2) cell apoptosis
      induced by ethanol and can be blocked effectively by Bcl-2 adenovirus vector.

PMID- 10951623
TI  - [Effects of ischemic preconditioning on apoptosis of hepatocytes in liver
      transplantation in rats].
AB  - OBJECTIVE: To evaluate the effects of ischemic preconditioning (IP) on hepatocyte
      apoptosis in ischemia/reperfusion injury of grafted liver and clarify its
      mechanism. METHODS: Orthotopic liver transplantation with cuff anastomosing
      method for the portal vein, suprahepatic vena cava and infrahepatic vena cava in
      the rats were divided into two groups: with and without IP treatment. The
      parameters of liver function were determined by auto-biochemical analyser. The
      concentrations of malondialdehyde (MDA) were measured with chromometry. The
      apoptotic hepatocytes in grafts liver were detected by flow cytometry combined
      with the in situ terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick
      end-labeling (TUNEL) method. RESULTS: The levels of AST, ALT, LDH in the serum,
      and MDA and apoptotic cells in the liver were significantly increased compared
      with normal values after ischemia/reperfusion to the grafted liver. After IP
      treatment, the levels of AST, ALT, LDH, MDA and apoptotic cells were
      significantly decreased. CONCLUSION: IP can attenuate ischemia/reperfusion injury
      by alleviating lipid peroxide and decreasing apoptosis of hepatocytes.

PMID- 10951624
TI  - [Induction of apoptosis in human hepatocellular carcinoma cells by adenoviral
      mediated transfer of human multigenes].
AB  - OBJECTIVE: To investigate the apoptosis induced by adenovirus-mediated
      transduction of human genes (p53, B(7-1), GM-GSF, IL-2) in liver cancer cells and
      the effects of tumorigenicity in nude mice. METHODS: Using light microscopy and
      electron microscopy and TUNEL assay, apoptosis in Ad-multigenes-transduced liver
      cancer cell lines was detected. The tumorigenicity of HepG(2) cells transduced
      with Ad-multigenes was detected. RESULTS: Ad-multigenes could induce apoptosis,
      and elevated sensitivity of human liver cancer cells to chemotherapy drugs. After
      cells with transduced Ad-multigenes were treated with 10mg/L cisplatin for 24 h,
      apoptosis was seen in nearly 30% of them. The tumorigenicity of Ad-multigenes
      transduced was reduced. CONCLUSION: Apoptosis induced by adenovirus-mediated
      multigenes acts synergetically with cisplatin in promotion of inducing apoptosis
      in liver cancer cell lines.

PMID- 10951622
TI  - [The influence of epidermal growth factor, neurotensin on cytosolic calcium and
      membrane fluidity in carbon tetrachloride-injured primary cultured hepatocytes].
AB  - OBJECTIVE: To study the influence of epidermal growth factor (EGF), neurotensin
      (NT) on cytosolic calcium and membrane fluidity in carbon tetrachloride-injured
      primary cultured hepatocytes. METHODS: A micro-model of carbon tetrachloride 
      induced primary cultured hepatocytes injury was established. EGF and NT were
      added to the cells 1 h ahead of carbon tetrachloride given. Twenty-four hours
      later, cytosolic calcium and membrane fluidity in hepatocytes were detected with
      fluorescence probe of Fura-2/AM and 1, 6-dihenyl-1, 3, 5-hexatriene (DPH).
      RESULTS: EGF and NT could significantly antagonize the increase of cytosolic
      Ca(2+) and decrease of membrane fluidity in carbon tetrachloride-injured
      hepatocytes. CONCLUSION: EGF and NT have a function of maintaining membrane
      fluidity and steady-status of cytosolic calcium of hepatocytes.

PMID- 10951626
TI  - [Comparison of the expression and activity of phosphatidylethanolamine N
      methyltransferase 2 between primary cultured hepatocytes and hepatoma cells in
      rats].
AB  - OBJECTIVE: To compare the expression and activity of phosphatidyl-ethanolamine N
      methyltransferase 2 (PEMT(2)) between the primary cultured hepatocytes and
      CBRH7919 hepatoma cells in rats. METHODS: The expression and activity of PEMT(2)
      were demonstrated by immunochemistry, Western immunoblotting and [(3)H-CH(3)] SAM
      incorporation. Flow cytometry (FCM) was used to investigate the DNA content of
      the cells. RESULTS: PEMT(2) expression and activity were higher in the primary
      cultured hepatocytes than in hepatoma cells. Cell cycle analysis showed that the
      proportion of the hepatocytes was higher in G(1) phase and lower in S phase in
      the primary cultured hepatocytes than hepatoma cell lines. CONCLUSION: There is
      an intimate relationship between the expression of PEMT(2) and the proliferation
      of hepatocytes.

PMID- 10951625
TI  - [Comparative studies of different carriers and introducing routes on the effects
      of liver targeted uptake of exogenous gene].
AB  - OBJECTIVE: To compare the effects of liposomes and glyco-poly-L-lysine (G-PLL) on
      target uptake and gene expression of the liver, and to observe the effects of
      intravenous route and intraperitoneal route on target uptake and gene expression
      of the liver. METHODS: After encapsulated by liposomes or galactose-terminal
      glyco-poly-L-lysine, the plasmid which can be expressed in eukaryotic cells was
      transferred into rat's body by intravenous injection and peritoneal injection
      respectively, then observed the results in different time by in situ
      hybridization and immunohistochemistry. RESULTS: The expression of the plasmid
      encapsulated by liposomes or G-PLL was obvious after transferred in vivo 24 h
      later, and one week later the expression began to decrease, but still could be
      found three weeks later. Both liposomes and G-PLL made the liver as the major
      distribution tissue. In the liver, the distribution and expression of the plasmid
      encapsulated by G-PLL were higher than those encapsulated by liposomes; in other
      tissues, however, the distribution and expression of the plasmid encapsulated by
      G-PLL were lower than those by liposomes. The distribution and expression of the
      plasmid transferred via intravenous route were higher in the liver than that
      transferred via intraperitoneal route. CONCLUSION: The effect of G-PLL on liver
      target uptake and expression is better than that of liposome; The effect of
      intravenous route on liver target uptake and expression of the plasmid binding to
      G-PLL is better than that of peritoneal route.

PMID- 10951627
TI  - [Expression of CPP32, Fas and Fas ligand and the relationship between their
      expression and viral antigens in chronic hepatitis].
AB  - OBJECTIVE: To study the significance of Fas-Fas ligand (FasL)-CPP32 mediated
      hepatocytic apoptosis and the relationship between their expression and hepatitis
      C virus (HCV) antigens in pathogenesis of chronic hepatitis C (CHC). METHODS: The
      expression of Fas and FasL proteins and CPP32 protease and their mRNAs was
      detected by immunohistochemistry and in situ hybridization respectively.
      Meanwhile, HCV core protein and nonstructural protein NS(3) and NS(5) were
      examined on the sequential liver tissue sections from 65 cases of patients with
      CHC and 5 cases of normal subjects. The positive staining was quantified by image
      analysis. RESULTS: In CHC liver tissues, CPP32 protease, Fas and their mRNAs were
      mainly expressed in the hepatocytes, especially in the HCV core protein-positive
      hepatocytes and their surroundings, but FasL protein and its mRNA were expressed
      dominantly in the infiltrating mononuclear cells in the portal area and hepatic
      sinusoid. According to the increase of histological activity index (HAI) in the
      CHC liver tissues, the expression of the three proteins (protease) and their
      mRNAs were upregrulated obviously. CONCLUSION: The results suggest i) that Fas
      FasL-CPP32 system is associated with HAI of CHC, ii) that HCV core antigen may
      affect the expression of CPP32 and Fas hepatocytes apoptosis.

PMID- 10951628
TI  - [The role of membrane-type 1 matrix metalloproteinase in the invasion and
      metastasis of hepatocellular carcinoma].
AB  - OBJECTIVE: To study the role of membrane-type 1 matrix metalloproteinase (MT(1)
      MMP) in the invasion and metastasis of hepatocellular carcinoma (HCC), and find a
      method to judge the invasion and metastasis of HCC through MT(1)-MMP. METHODS: RT
      PCR was used to study the expression of MT(1)-MMP mRNA in the HCC and in HCC nude
      mice model with higher metastasis potential (LCI-D20) and lower metastasis
      potential (LCI-35), and statistical methods were used to analyse the association
      between the expression of MT(1)-MMP mRNA and the pathological indexes of HCC.
      RESULTS: MT(1)-MMP mRNA was expressed by all the normal liver tissue (1.12 +/-
      0.73), HCC (3.51 +/- 0.97), surrounding liver parenchyma (1.19 +/- 0.57), tumor
      embolus, and HCC nude mice model with LCI-D20, LCI-D35. The overexpression of
      MT(1)-MMP mRNA in HCC, embolus, LCI-D20 was related to the invasion and
      metastasis of HCC. The expression of MT(1)-MMP mRNA in HCC being higher than that
      in surrounding liver parenchyma was an important index to judge the invasion and
      metastasis of the HCC. CONCLUSION: MT(1)-MMP is related to the invasion and
      metastasis of HCC. The expression of MT(1)-MMP mRNA in HCC being higher than that
      in surrounding liver parenchyma could be acted as an important index to judge the
      invasion and metastasis of HCC.

PMID- 10951629
TI  - [Effect of domestic glutathione on the alcoholic liver disease].
AB  - OBJECTIVE: To evaluate the effect and safety of domestic glutathione (GSH) on
      serum ALT, AST, SB levels in alcoholic liver disease (ALD) by multicenter,
      randomized and TAD controlled trial. METHODS: All the 110 patients with ALD
      enrolled had a history of drinking over 80g-120g daily for 5 years, and were
      randomized either into GSH (continuous infusion of 600g daily for 30d) or TAD
      (with the same dosage, course and route as GSH) group. The efficacy and safery
      were evaluated with clinical and biochemical (ALT, AST and GGT) parameters.
      RESULTS: After 8 weeks of treatment, the clinical signs were improved at a
      different degree in both groups. ALT, AST and SB showed no significant difference
      in the two groups (the efficacy rate of 93% vs 96%, P>0.05). CONCLUSION: The
      domestic GSH, with a good tolerance and safety, has a sound efficacy in the
      improvement of clinical signs and hepatic functions.

PMID- 10951630
TI  - Neonatal cholestasis syndrome- the saga continues.

PMID- 10951631
TI  - Clinical spectrum of HIV infection.
AB  - OBJECTIVE: To study the modes of transmission of pediatric HIV infection, to
      categorize clinical manifestations and to compare clinical spectrum of perinatal
      with transfusion acquired HIV infection. DESIGN: Case series study. SETTING:
      Hospital based pediatric HIV clinic. METHODS: Children confirmed to have HIV
      infection were evaluated and relevant details recorded. RESULTS: 55 children were
      enrolled of whom 41 (74.5%) had perinatal transmission of HIV, 12 (21.8%) were
      infected through blood transfusions and 2 (3.6%) through other routes. Thirty
      seven (90.2%) of the 41 perinatally infected children were symptomatic.
      Tuberculosis was seen in 25 (67.5%) of these children and failure to thrive in 18
      (48.6%). Nonspecific features such as recurrent bacterial infection, oral
      candidiasis and chronic diarrhea were other manifestations. Eight (26.3%) of the
      30 children available for follow up for a median period of 9 months died at the
      median age of 8.5 months. Amongst the transfusion acquired HIV infection, 11
      (91.6%) of the 12 were asymptomatic at presentation. Six (50%) of these children
      died at the median age of 3 years and the remaining 6 had no major symptoms at a
      median follow up of 3.5 years. CONCLUSION: Perinatal route is the major route of
      HIV transmission in children and clinical manifestations are different from those
      of adults.

PMID- 10951632
TI  - A double-blind placebo-controlled study on prophylactic use of cisapride on feed
      intolerance and gastric emptying in preterm neonates.
AB  - OBJECTIVE: To evaluate whether prophylactic use of cisapride will reduce the
      incidence of feed intolerance and gastro-esophageal reflux, and improve gastric
      emptying in early neonatal period in preterm babies. DESIGN: Double blind
      randomized controlled trial. SETTING: Hospital based. SUBJECTS: Forty nine
      preterm babies between 29-34 weeks of gestation were administered either
      cisapride or placebo. METHODS: Babies were enrolled in the study once they
      reached 30 ml/kg/day of enteral feeding or when 25% of total fluid intake was
      received through the enteral route. Those with sepsis, congenital malformations
      and on aminophylline were excluded. The subjects were randomized to receive
      either cisapride or placebo in a dose of 0.2 mg/kg/dose every 8 hourly for 14
      days or till discharge. During the study period babies were observed for clinical
      signs of feed intolerance as judged by increase in abdominal girth, increased
      prefeed gastric residuals or vomiting. Gastro-esophageal reflux and gastric
      emptying time was assessed by Technetium phytate scan on day 7 +/- 1. RESULTS:
      Feed intolerance was noticed in 59% of study and 41% of control population. No
      significant difference was noticed in the two groups in the total number of
      episodes of feed intolerance (1.54 +/- 2.4 vs 1.18 +/- 1.6). Nearly 50% of babies
      in each group had gastro-esophageal reflux. Gastric emptying time (mean (SD) and
      median) was found to be comparable (p = 0.70) in those on drug and placebo (58.1
      (32.2 min) 48.8 min) vs (53.8 (34.6 min) 43.4 min). CONCLUSION: Cisapride does
      not reduce the incidence of feed intolerance, gastro-esophageal reflux and does
      not improve gastric emptying in normal preterm neonates.

PMID- 10951633
TI  - Consensus report on neonatal cholestasis syndrome. Pediatric Gastroenterology
      Subspecialty Chapter of Indian Academy of Pediatrics.

PMID- 10951634
TI  - Transfer of sick children by air.
AB  - The annual growth rate of air traffic is increasing at the rate of about 7% all
      over the world. Children and adolescents make a significant chunk of travelling
      population. Some of the neonates too take to civil air and travel under various
      circumstances. Others travel for the reasons of medical air evacuation and better
      treatment at some specialized tertiary care centers, within India or abroad or
      simply as medical emergency. With the increasing availability of air taxis and
      air ambulances, it has become necessary for the pediatricians to know the
      consequences and potential hazards of transfer of the sick by air, lest they lose
      their patients unintentionally despite professional proficiency. Air evacuation
      of sick child is a highly specialized job, much different from an evacuation by
      any fast car ambulance. The paper discusses the general impact of aviation
      stresses in civil aviation with special reference to sick neonates, children and
      adolescents, and provides general guidelines, which could be applied to any
      particular clinical condition with knowledge of underlying physiological
      processes and anticipated alterations in cabin environment. It also brings out
      the issues of proper pre-flight assessment, fitness to undertake air transfer,
      general handling of patient under transfer, desirable onboard procedures, do s
      and don ts during air transfer, limitations of conventional neonatal/child
      resuscitation kits, available medical support in aircraft cabins, proper use of
      hardware including physiology monitoring systems, permissible specialized medical
      aids, and the requirement and use of equipment during air evacuation. The
      importance of high awareness and preventive measures is reiterated.

PMID- 10951635
TI  - Socioeconomic and demographic factors associated with birth weight: a community
      based study in Kerala.

PMID- 10951636
TI  - Recurrent abdominal pain--a reappraisal.

PMID- 10951637
TI  - Seroconversion after hepatitis B vaccination in children receiving cancer
      chemotherapy.

PMID- 10951638
TI  - Urinary tract infection in infants and young children with diarrhea.

PMID- 10951639
TI  - Persistent hyperinsulinemic hypoglycemia with pyloric stenosis.

PMID- 10951640
TI  - Langerhans cell histiocytosis involving the urinary bladder.

PMID- 10951641
TI  - Dandy Walker Syndrome associated with unusual congenital anomalies.

PMID- 10951642
TI  - Focal segmental myelitis.

PMID- 10951644
TI  - Timing of booster of rabies vaccine.

PMID- 10951646
TI  - Age limit for polio vaccine.

PMID- 10951648
TI  - Granuloma annulare.

PMID- 10951643
TI  - Spontaneous neonatal esophageal perforation.

PMID- 10951649
TI  - Hunter syndrome.

PMID- 10951650
TI  - Oxygen administration to a baby in styropor box.

PMID- 10951651
TI  - Status of micronutrients in malnutrition before and after rehabilitation.

PMID- 10951652
TI  - Polio eradication strategy: need for re-appraisal.

PMID- 10951653
TI  - Cisapride for the treatment of constipation in children.

PMID- 10951655
TI  - First anniversary of the first electronic peer-reviewed pharmaceutical sciences
      journal.

PMID- 10951654
TI  - Drugs for pain.

PMID- 10951656
TI  - Pharmacokinetics tricks and traps: drug dosage adjustment in renal failure.

PMID- 10951657
TI  - Sustained release and enteric coated NSAIDs: are they really GI safe?
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have commonly been associated with
      upper gastrointestinal (GI) tract side effects including a high incidence of
      gastric and duodenal ulceration. Recent reports implicate NSAID use and mucosal
      injury in the small and large intestine. A trend in NSAID development has been an
      attempt to improve therapeutic efficacy and reduce the severity of upper GI side
      effects through modified release dosage forms of NSAIDs such as enteric-coating
      (EC) or sustained release (SR) formulations. It is possible that modified release
      formulations may increase the exposure of active drug to the mucosa distally to
      the duodenal bulb, and thereby increase toxicity to distal GI regions where the
      effects are difficult to monitor. A systematic literature review through Medline,
      Embase, and Index Medicus was made to identify toxicological effects induced by
      modified release formulations of NSAIDs in the small and large intestine. An
      analysis of the identified toxicological effects of these formulations was made.
      SR and EC NSAID use has been associated with both small and large intestinal
      bleeding, anaemia, strictures, ulcerations, perforations, and death. Modified
      release NSAIDs may cause significant morbidity in some patients. NSAID modified
      release delivery systems are not guarantors of GI safety. Since SR and EC NSAIDs
      are widely prescribed and some EC products are available without a prescription,
      heightened awareness of these toxicological manifestations in more distal sites
      of the GI tact may reduce morbidity.

PMID- 10951658
TI  - Are the current bioequivalence standards sufficient for the acceptance of narrow
      therapeutic index drugs? Utilization of a computer simulated warfarin
      bioequivalence model.
AB  - PURPOSE: The purpose of this computer simulation was to determine the likelihood
      of two bioequivalent (vs. reference) generic warfarin formulations (with varying
      bioavailability) passing current bioequivalence criteria against each other at
      varying bioavailability. Methods. A bioequivalence simulation program generated
      100 warfarin bioequivalence (BE) studies with 24 patients/study. The reference
      formulation (R) was assigned a bioavailability of 90%. In these simulations the
      first generic (G(1)) had a bioavailability that was incrementally decreased from
      90%. The second generic (G(2)) had a bioavailability that was incrementally
      increased from 90%. The bioequivalence testing was performed initially as G(1
      )vs. R, then G(2) vs. R, and finally G(2) vs. G(1). The tests were performed
      according to current criteria for therapeutic index drugs. RESULTS: 5400 BE
      studies with a total of 129,600 subjects and 2,462,400 sampling times were
      simulated. When G(1) vs. R was compared, fewer than 80% of studies passed when
      the relative AUC(0-t )ratios were 88% or less. When G(2) vs. R were compared,
      fewer than 80% of studies passed when the relative AUC(0-t )ratios were 113% or
      greater. When Generic 2 and Generic 1 were compared fewer than 80% of studies
      passed when the relative AUC(0-t) ratios deviated from the reference by 7% or
      more. DISCUSSION Despite limitations this simulation indicates that two
      bioequivalent (vs. reference) generic warfarin products may not be bioequivalent
      to each other. Alternative methods of assessing bioequivalence are needed when
      more than one generic of narrow therapeutic index drug exists on the market.

PMID- 10951659
TI  - Disposition of ethopropazine enantiomers in the rat: tissue distribution and
      plasma protein binding.
AB  - PURPOSE: To determine the in vitro plasma protein binding, and the in vivo brain,
      heart and plasma concentrations of ethopropazine (ET) enantiomers in the rat
      after iv doses. METHODS: For in vivo assessment of ET enantiomer concentrations,
      rats with implanted jugular vein cannulae were injected with 10 mg/kg of (+/-)-ET
      HCl. At selected times after dosing, rats were sacrificed and heart, brain, and
      plasma were collected. Equilibrium dialysis was used to determine the unbound
      fraction of ET in rat plasma over a concentration range of 150 to 4000 ng/mL of
      each enantiomer. A stereospecific assay was used to measure concentrations of ET
      enantiomer. RESULTS: No stereoselectivity was observed in plasma or tissues after
      iv dosing. Area under the concentration vs. time curves indicated that highest
      uptake of ET occurred in brain tissue, followed by heart tissues, then plasma.
      There was no noticeable difference between concentrations of ET enantiomers in
      different parts of brain (substantia nigra, cortex, or striatum). There was no
      observed stereoselectivity in plasma protein binding of ET enantiomers in rat
      plasma. Saturation of binding to plasma proteins was observed between 500 and
      2000 ng/mL of each ET enantiomer, but unbound fraction was constant at
      concentrations below and above that range. CONCLUSION: Ethopropazine displays
      nonstereoselectivity in its pharmacokinetics. The drug shares distribution
      features similar to those of other phenothiazine derivatives. Based on the in
      vitro plasma protein binding results, there appears to be saturation of some, but
      not all, plasma binding proteins of ET within the range of concentrations
      studied.

PMID- 10951660
TI  - Methoxyflurane anesthesia augments the chronotropic and dromotropic effects of
      verapamil.
AB  - INTRODUCTION: Inhalation anesthetics have been shown to have electrical
      suppressant effects on excitable membranes such as the cardiac conduction system.
      Therefore, the anesthetized patient or laboratory animal may respond differently
      to cardiac drugs when compared with their conscious counterparts. The purpose of
      this study was to assess the effects of anesthesia with methoxyflurane (MF) on
      the dromotropic and chronotropic effects of verapamil (VER) in the rat. METHODS:
      A lead I ECG was measured using subcutaneous electrodes placed both axilli and
      over the xyphoid process in male Sprague-Dawley rats. Dromotropic effect was
      measured using the PR-interval which indicated the electrical spread across the
      atria to the AV-node and chronotropic effects were determined using RR-interval.
      A total of six animals were randomized to receive 10 mg/kg s.c. of verapamil in
      the presence or absence of general anesthesia containing methoxyflurane. In
      addition, PR-interval and RR-intervals were determined in the presence of only
      methoxyflurane and at rest without any drug exposure. The time for the ECG to
      normalize after exposure to methoxyflurane and/or verapamil was also determined.
      RESULTS: Exposure to verapamil alone resulted in a 5% prolongation in PR-interval
      and 6% prolongation in RR-interval. Methoxyflurane alone had a larger effect than
      verapamil demonstrating a 14.5% prolongation in PR-interval and a 12.3% in RR
      interval which was statistically significant. The combination of MF + VER
      resulted in a synergistic prolongation in PR-interval to 28. 7% while the effect
      on RR-interval was additive with an increase to 17.6%. The time for the ECG to
      normalize after exposure to VER, MF and VER + MF was 37.5 15.1 min, 69.8 5.3 min,
      and 148.5 +/- 6.6 min respectively. CONCLUSION: General anesthesia with MF
      enhances the dromotropic and chronotropic effect of VER. This should be
      considered when MF-anesthesia is used in experimental procedure.

PMID- 10951661
TI  - CC chemokine receptor 6 (CCR6) is a marker for memory T cells that arrest on
      activated human dermal microvascular endothelium under shear stress

PMID- 10951662
TI  - [Gliomatosis cerebri: clinico-pathological and neuroimaging characteristics and
      the results of treatment with radiotherapy].
AB  - INTRODUCTION: Gliomatosis cerebri is a rare form of malignant neoplastic glial
      transformation that involves large areas of the central nervous system.
      OBJECTIVE: To describe clinical manifestations, pathognomonic neuroimaging
      findings and results of radiotherapy of gliomatosis cerebri. PATIENTS AND
      METHODS: We review clinical records and neuroimaging studies of two patients with
      gliomatosis cerebri identified from the files of brain tumor registries of two
      university hospitals. One patient underwent radiotherapy after surgery. RESULTS:
      Clinical manifestations and evolution were totally different in both patients
      despite the fact that both tumors had the same extension on neuroimaging studies.
      Magnetic resonance imaging revealed the extent of the lesion in both cases,
      comprising both cerebral hemispheres. Histopathological study revealed G-I and G
      II astrocytomas. The patient treated with whole brain irradiation experienced
      clinical improvement and involution of the brain tumour on neuroimaging studies,
      and survived 20 months after surgery. CONCLUSIONS: Clinical manifestations of
      gliomatosis cerebri are protean. Therefore, neuroimaging studies and
      histopathological analysis of brain tissue allow the correct diagnosis.
      Radiotherapy may improve neurological function in some patients. However, it is
      necessary to compare the long-term evolution of treated and non-treated patients
      to evaluate clinical efficacy of radiotherapy.

PMID- 10951663
TI  - [Neurological evolution of asphyctic full-term newborns with severe umbilical
      acidosis (pHUA <7.00)].
AB  - INTRODUCTION AND OBJECTIVE: Umbilical arterial blood pH (pHUA) has become
      increasingly recognized as the most reliable indication of foetal oxygenation and
      acid-base condition at birth. In term infants pHUA is a poor predictor of newborn
      complications associated with perinatal asphyxia (PA), unless the pHUA is less
      than 7.00. The objective of this article is to analyse the neurologic evolution
      of asphyctic full-term newborns with severe umbilical acidosis (pHUA < or =
      7.00). PATIENTS AND METHODS: One hundred and eighty consecutive asphyxiated term
      infants were studied during 64 months, and classified in two cohorts: G1 (pHUA <
      or = 7.00, n = 18) and G2 (pHUA > 7.00, n = 162). Variables prospectively
      obtained on standard protocol forms from the medical records were derived from a
      detailed review of the obstetric record, the delivery room management, the
      detailed neonatal clinical history and the postneonatal follow-up. The perinatal
      variables were graded as prenatal (gestational and obstetric), neonatal
      (resuscitation, general data of the newborn, and organic manifestations of
      asphyxia) and postneonatal (neurologic sequelae with at lest 24 months of follow
      up). PA was graded as severe and non-severe, hypoxic-ischemic encephalopathy was
      based on Levene's criteria, and neurologic sequelae were based on Finer and Amiel
      Tisson's criteria. RESULTS: An umbilical artery pH value < or = 7.00 occurred in
      0.3% of the total live full-term newborns. In G1 the mean pHUA value was 6.93 +/-
      0.06 (range 6.80-7.00) and in G2 the mean pHUA value was 7.17 +/- 0.09 (range
      7.01-7.46). The incidence of severe PA was significantly increased in G1 (RR =
      4.74, CI 95% = 2.62-8.55, p < 0.001), with more postasphyctic neurologic (RR =
      3.72, CI 95% = 2.34-5.92, p < 0.001) and extraneurologic (RR = 3.13, CI 95% =
      1.65-5.94, p < 0.01) involvement. But we do not found differences in the
      incidence of neurologic sequelae between both cohorts. CONCLUSIONS: Term
      asphyctic newborns with severe umbilical acidosis have worse evolution at short
      term (more clinical involvement during neonatal period), but not worse evolution
      at long term (neurologic sequelae). The poor correlation between umbilical
      acidosis and neurologic prognosis persist when pHUA cut-off is < or = 7.00.

PMID- 10951664
TI  - [The importance of postnatal risk factors in localized epilepsies].
AB  - INTRODUCTION: The risk factors for epilepsy are not sufficiently well known.
      OBJECTIVES: To determine the postnatal risk factors for epilepsy related to
      localization. PATIENTS AND METHODS: We studied 100 patients with localized
      epilepsy who were over 14 years old, randomly selected and consulted us between
      January 1996 and July 1997. Data was obtained using the specific protocol of an
      epileptology program. All patients had electroencephalograms and skull
      tomography. RESULTS: The average age was 29 years. There were more males than
      females (57 males) and simple partial crises with secondary generalization were
      the commonest (49 patients). Head injury was the main risk factor. CONCLUSIONS:
      Postnatal risk factors which could have been avoided, such as head injury and
      neurocysticercosis made up the main group of patients with factors identified.
      Alterations on skull tomography were associated with statistically significant
      postnatal risk factors.

PMID- 10951665
TI  - [Hypothalamic hamartomas: control of seizures after partial removal in one case].
AB  - OBJECTIVE: To describe a patient with intractable seizures and hypothalamic
      hamartoma that was only partially resected with complete control of seizures and
      improvement in behavior after surgery. CLINICAL CASE: He had gelastic seizures
      from the first months of life associated with hypothalamic hamartoma. We used
      magnetic resonance spectroscopy to localize and measure the lesion in the
      temporal lobes and in the hamartoma. The relative intensity of N-acetylaspartate
      to creatine (NAA/Cr) and NAA/choline (Ch) were not significantly different from
      normal control subjects for either temporal lobes, whereas the ratio NAA/Ch was
      decreased and the ratio NAA/Cr was highly increased in the hamartoma. Despite
      only partial resection of the hamartoma, seizures have been completely controlled
      and the patient has recovered normal social and work activity and is ending a
      normal life, that follow three years after surgery. CONCLUSIONS: These findings
      suggest that gelastic seizures associated with hypothalamic hamartoma are
      generated within the hamartoma itself, and that it is possible to control
      epilepsy and to improve intellectual and social problems with only partial
      resection of the mass.

PMID- 10951667
TI  - [Down's syndrome and dementia].
AB  - OBJECTIVE: To review the relationship between Down's syndrome and Alzheimer's
      disease. DEVELOPMENT: Down's syndrome is the commonest autosomopathy. Its
      clinical features permit easy diagnosis. Control of the more severe
      complications, such as cardiac malformations have allowed prolonged survival. The
      presence of neuropathological findings similar to those in Alzheimer's disease is
      almost constant in the brains of patients aged over 40 years with Down's
      syndrome. Dementia appears in a third of these patients. In this article we
      comment on the diagnostic difficulties, possible risk factors and the importance
      of findings related to chromosome 21. We also evaluate the results of new
      treatments with cholinesterase inhibitors. CONCLUSION: The study of the close
      relationship between Down's syndrome and Alzheimer's disease should allow us to
      advance understanding of both of these conditions.

PMID- 10951666
TI  - [Cerebral ischemia following varicella. A case report].
AB  - INTRODUCTION: Varicella in childhood is a self-limiting disease which usually
      follows a benign course. However, a considerable number of complications occur,
      particularly involving the nervous system. On rare occasions hemiparesis has been
      reported following an ischemic cerebrovascular accident related to varicella.
      CLINICAL CASE: We report the case of a 4 year old boy who presented with right
      hemiparesis eight days after the onset of varicella. CAT and MR showed a cerebral
      infarct involving the left caudate nucleus, putamen and internal capsule. Other
      possible causes of cerebral infarct were ruled out. Four years later he had
      slight residual right hemiparesis. The pathogenesis may have been due to
      vasculitis of the intracranial arteries caused by direct invasion of the vessels
      by virus from the nearby nerve tissue. Another theory suggest similarities with
      moyamoya disease, suggesting that lesions of the head and neck stimulate the
      superior cervical ganglion and this, together with the production of circulating
      immuno-complexes may be the cause of the vasculopathy of the intracranial blood
      vessels. CONCLUSIONS: In most cases of cerebrovascular accidents occurring in
      childhood the cause is unknown. However, it is important to discover the cause
      since the risk of recurrence often depends on the primary disease. Once other
      commoner causes have been excluded, one should ask whether there is a history of
      varicella, since the prognosis is generally good and recurrence uncommon.

PMID- 10951668
TI  - [Prions and their biology].
AB  - Prion diseases or transmissible spongiform encephalopathies are fatal
      neurodegenerative disorders featured by an aberrant metabolism of a cellular
      membrane glycoprotein, the prion protein (PrP-C). PrP-C is being related to Cu
      (II) homeostasis and postulated as candidate for cell signaling and cell adhesion
      functions. Under pathological conditions PrP-C converts into a conformational
      isomer (PrP*, PrP-res, PrP-Sc, PrP-Creutzfeldt-Jakob disease, etc.). In addition
      to divergent biochemical characteristics, the latter form displays the property
      of recognizing the normal protein and transforming it into its homologue.
      Conversion process is ill tangled and participation of yet unidentified partners
      has been postulated.

PMID- 10951669
TI  - [Transmissible spongiform encephalopathies in animals].
AB  - INTRODUCTION: The transmissible spongiform encephalopathies affect several
      species of higher animals apart from man. Amongst these, undoubtedly the best
      known is that affecting cattle, since the association between consumption of beef
      and its derivatives and the appearance of a variant of Creutzfeldt-Jakob disease
      in humans has been established. DEVELOPMENT: This type of pathology has been well
      known for many years in the ovine family, particularly in sheep and goats. In
      spite of the establishment of hypotheses linking the cause of the appearance of
      spongiform encephalopathy in cows with an interspecies jump of the disease
      between the ovine and bovine families, this has not yet been proved. Concomitant
      with the epidemic of bovine spongiform encephalopathy, other species of animals
      were reported to have been affected by an identical disease. These included
      farmed mink, deer, elks, cats and two species of exotic African ungulates (the
      nyala and the greater kudu). All cases were described in animals kept in
      captivity for human consumption. Thus it would seem that there was a common cause
      of the disease in all cases. CONCLUSION: In this paper we describe the most
      relevant aspects of the appearance of this disorder in animals, including the
      symptoms, epidemiology and pathology typical of each specific condition.

PMID- 10951670
TI  - [The history and classification of human prion diseases].
AB  - INTRODUCTION AND DEVELOPMENT: The history of prion diseases is one of the most
      exciting chapters of the story of medicine in the twentieth century. It began in
      the nineteen twenties when Creutzfeldt (in one patient) and Jakob (in five
      patients) described a clinically polymorphic cerebral syndrome with a subacute or
      chronic course and fatal outcome. Although later reviews of these pioneer studies
      have cast doubt on the nosology of some of these cases, the eponym has been
      maintained over the years. It is even possible that the miliary sclerosis
      described by Gowers in the nineteenth century was in fact a spongiform
      encephalopathy. Subsequently the nosological limits of Creutzfeldt-Jakob disease
      remained ill-defined. This explains the large number of names given to it whilst
      it continued to be included in the chapter on degenerative conditions of the
      nervous system. Perhaps the turning point was when, in the nineteen sixties,
      Carleton Gajdusek et al showed that it was transmissible. Previously Gajdusek and
      Zigas had (in 1957) described the disease kuru in a group of indigenous cannibals
      in Papua (New Guinea). The possibility of a parallel between this kuru and the
      scrapie of sheep (in which transmission had been proved twenty years before) led
      them to experiment and eventually prove its infectious nature. Over the following
      years, reports of iatrogenic cases with different routes of transmission gave
      further proof. The absence of conventional microorganisms responsible for this
      group of conditions led Prusiner (in 1982) to suggest the theory of the infecting
      proton or prion. CONCLUSION: This theory led to better understanding of several
      pathological and physiopathological aspects, however, we are aware that the full
      story of prion diseases is still being written at the present time.

PMID- 10951671
TI  - [Chronology of the new variant of Creutzfeldt-Jakob disease].
AB  - INTRODUCTION: The appearance of a new variant of Creutzfeldt-Jakob disease, and
      the particular conditions of this appearance, have caused a minor scientific and
      social upheaval in Europe. The possible relation between it and the epidemic of
      bovine spongiform encephalopathy in the United Kingdom led to a real scientific
      'race against time' to discover the agent causing the two conditions and a
      possible link between them, and made the rare group of diseases known as prionic
      diseases fashionable. DEVELOPMENT: The aim of this article is to describe the
      development of events concerning the appearance of this condition, considering
      them objectively from the point of view of an outside observer. We discuss the
      different phases of the story, from the initial perplexity at the appearance of
      the epidemic of bovine spongiform encephalopathy, followed by uncertainty when
      the new variant of Creutzfeldt-Jakob disease was described and the possible
      relation between the two conditions. CONCLUSION: Everything concerning this
      process, including the different attitudes and opinions of the social, political
      and scientific groups involved, could form the plot of a top best selling novel
      of the moment.

PMID- 10951672
TI  - [Sleep disorders associated to prion diseases].
AB  - INTRODUCTION: Description of sleep disorders associated to human prion diseases.
      DEVELOPMENT: The recent advances on pathology, genetics and immunocytochemistry
      are an outstanding contribution to the knowledge of transmissible spongiform
      encephalopathies and identification of possible new variants. Despite decades of
      research, human prion diseases have remained enigmatic in many aspects. Among
      these, the intricate connection between infectivity and genetics, genotype
      phenotype correlation, pathogenesis of brain damage and in some cases its proven
      dependence on the genotypic combination of a pathogenic mutation and a
      polymorphism. Regarding this subject we should take into consideration that Fatal
      Familial Insomnia (FFI) appears as an ideal model situation for answering some of
      these problems because of its distinctive clinicopathological phenotype based on
      a specific genotype as well as its transmissibility. This disease has recently
      enlarged the group of prion diseases. It is linked to a mutation at codon 178 of
      the prion protein gene, coupled with the methionine codon at position 129, the
      site of a methionine/valine polymorphism. The clinical aspects of FFI include a
      peculiar sleep-wake disorder and a autonomic hyperactivity associated with
      vegetative and hormonal circadian rhythm disregulation, besides cognitive and
      motor alteration, and it is related to the selective atrophy of limbic part of
      the thalamus. EEG conventional sleep studies and 24-hour polygraphic recordings
      can provide proof of early disappearance sleep spindles and the disturbances of
      sleep, which typify the disease. Epidemiologic, pathophysiologic, and
      histopathological aspects are also mentioned. Finally we remark the major
      neurophysiological features of Creutzfeldt-Jakob disease and Morvan's chorea.

PMID- 10951673
TI  - [Electroencephalography in Creutzfeld-Jakob disease].
AB  - INTRODUCTION: The electroencephalogram is very useful in the diagnosis of
      probable Creutzfeldt-Jakob disease. DEVELOPMENT: It is considered that a typical
      pattern is formed of periodic sharp wave complexes, widely distributed
      (synchronously and symmetrically) over both cerebral hemispheres. The frequency
      of presentation is approximately 1/second. However during the course of the
      disease other patterns are seen, such as frontal intermittent rhythmical delta
      activity, a cyclical alternating pattern and a low output electroencephalogram.
      CONCLUSION: Recognition of these patterns, their electroclinical correlation and
      serial polygraphic studies are very important to the reliability of the test.

PMID- 10951674
TI  - [Immunohistochemistry techniques in prion diseases].
AB  - The prion diseases are characterized by showing a broad spectrum of phenotypes
      with different clinical and neuropathological presentations. Detection of the
      prion protein is the marker used as a tool for making the definite diagnosis in
      these neurodegenerative diseases. Its presence may be detected by
      immunohistochemical and biochemical techniques. On immunohistochemical studies
      the prion protein shows three types of staining: as plaques of PrP-amyloid,
      perivascular and diffuse-synaptic.

PMID- 10951675
TI  - [Neuropathology of the new variant of Creutzfeldt-Jakob disease].
AB  - Identification in the United Kingdom of cases of Creutzfeldt-Jakob disease with
      clinical, genetic, neuropathological and phenotype characteristics different from
      those previously reported, together with its relation to bovine spongiform
      encephalopathy led to the establishment of a new condition known as a new variant
      of Creutzfeldt-Jakob disease. In this article we describe the neuropathology and
      immunohistochemistry of the prion protein involved.

PMID- 10951676
TI  - [Measures for the security from and prevention of prion diseases].
AB  - INTRODUCTION: The rarity of prion diseases in this country makes it difficult to
      remember and put into practice specific preventive measures in suspected and
      diagnosed cases. DEVELOPMENT AND CONCLUSIONS: In this article we update and
      review aspects of hospital transmission, and establish the measures of prevention
      and security which should be used in a general setting, including aspects of the
      care of these patients, cleaning, disinfecting and sterilizing the material used,
      and disposal of any residues. We suggest specific preventive measures for
      Units/Departments in which these patients are most often attended, including
      aspects of the workplace as dealt with by European and Spanish regulations,
      establishing the rights and obligations of both employers and employees, and the
      measures to be taken in the case of an accident at work.

PMID- 10951677
TI  - [The future and problems of vigilance in Creutzfeldt-Jakob disease].
AB  - INTRODUCTION: The epidemiological surveillance of human transmissible spongiform
      encephalopathies, is heavily dependent on diagnostic quality, requires therefore
      a dynamic health care system able to incorporate new diagnostic tools, and rests
      on activities within three major observation fields: study of age-specific
      incidences of the disorder, identification of possible changes in clinico
      pathological profile, particularly, of variant Creutzfeldt-Jakob disease, and
      analysis of incidences among the young population with codon 129VV. Problems for
      evaluating potentially emerging disorders are determined by increasing awareness
      of diagnosis, changes in autopsy rates, appropriate use of the 14-3-3 protein
      test in CSF test and international variations in expected data. DEVELOPMENT: The
      situation in Spain with increasing incidences among the elderly might reflect the
      impact of recent changes in use of new diagnostic tests, increasing diagnostic
      awareness of the clinicians among the elderly and a drop in autopsy rates since
      1996. Systematic use of 14-33-test in suspected cases, genotyping, and post
      mortem study practice, as well as international collaboration are recommended for
      optimal surveillance. The importance of compulsory notification by law is
      debated. Generous notification of suspected cases to Instituto de Salud Carlos
      III, Centro Nacional de Epidemiologia is kindly requested.

PMID- 10951678
TI  - [The advantages of a stroke unit in the treatment of intracerebral hemorrhage].
AB  - INTRODUCTION: The efficacy of a stroke unit in the management of acute
      cerebrovascular disease has, in general, been widely demonstrated. Our analysis
      seeks to determine whether this efficacy is maintained in intracerebral
      hemorrhage. PATIENTS AND METHODS: We studied the patients with intracerebral
      hemorrhage attended in the Neurology Department by the stroke team in 1994 and
      during the first years of its activity (1995-1996), analysing the average time of
      stay, complications, functional state and destiny of the patient after discharge.
      RESULTS: We recorded 151 patients (58 in 1994, 46 in 1995 and 57 in 1996) who
      made up 10.1% of the total number of strokes. We observed a significant reduction
      in average stay (p < 0.01), with improved score on the Rankin scale at the time
      of discharge (p < 0.005). Similarly there were fewer complications and those
      statistically significant were: hydrocephaly (p < 0.05), rebleeding (p < 0.05),
      sepsis (p < 0.1) and renal failure (p < 0.01). Discharge home remained stable
      although there was a significant increase in transport of patients to
      rehabilitation centres (p < 0.05) and reduction in patients sent to long-term
      care institutions. CONCLUSIONS: The specific integrated care given by stroke unit
      result in improved course of the illness in patients with intracerebral
      hemorrhage, with fewer complications, reduced hospital stay, better functional
      state and better possibilities of rehabilitation after discharge.

PMID- 10951679
TI  - [The medical treatment of intracerebral hemorrhage].
AB  - OBJECTIVE: To review the main aspects of the practical management of
      intracerebral hemorrhage. DEVELOPMENT: We begin by briefly reviewing the
      pathophysiology, clinical features and recommended complementary investigations
      which are necessary for satisfactory diagnosis and treatment. These vary
      depending on the characteristics of the bleeding on neuroimaging, age and
      clinical situation of the patient. We particularly consider the therapeutic
      aspects, basically of medical treatment but also some aspects of surgical
      treatment, both during the acute phase of bleeding, when the main objective is to
      prevent and treat the neurobiological and systemic complications, such as the
      specific underlying disorder or lesion causing the intracerebral hemorrhage, so
      as to prevent further bleeding. THE MEDICAL TREATMENT: General measures,
      mechanical ventilation, control of blood pressure, the prevention and treatment
      of raised intracranial pressure and the possibilities of specific medical
      treatment in reducing the zone of ischemic penumbra are also reviewed. Since
      surgical treatment is controversial, we have considered the most generally
      accepted indications for this and the different techniques used. Finally we
      review the risk factors identified in cerebral hemorrhage which permit primary
      prevention.

PMID- 10951680
TI  - [Blood flow in patients with intracerebral hemorrhage. Does there exist the
      associated hypoperfusion? A transcranial Doppler study].
AB  - OBJECTIVE: To evaluate, using transcranial Doppler, changes in parameters in
      patients with cerebral hematoma, as compared with controls, for detection of
      possible regional hypoperfusion. PATIENTS AND METHODS: We studied 24 patients
      with cerebral hematomas and 15 healthy volunteers. The volume of the hematoma and
      the hypodense area was determined by computerized axial tomography of the skull
      at the time of admission. The average speed and index of pulsation of the
      anterior, middle and posterior cerebral arteries were measured in both
      hemispheres using transcranial Doppler within the first 100 hours. The
      differences between the averages were analysed using the ANOVA test and the
      correlations with Pearson's coefficient of correlation. RESULTS: The average
      speeds, except in the anterior cerebral artery, were lower in both hemispheres in
      the patients than in the controls (p < 0.001). There were interhemispherical
      differences in the average speeds in the patients (p = 0.06). The indices of
      pulsatility were greater in both hemispheres in the patients than in the controls
      (p < 0.001). These differences were independent of age, sex and arterial blood
      pressure. The average speed in the ipsilateral middle cerebral artery showed
      excellent correlation with the size of the hypodense area (r = -0.92) and the
      hematoma (r = -0.89). The indices of pulsatility showed little correlation with
      the size of the lesion. There was moderate correlation between transcranial
      Doppler and clinical scales. CONCLUSION: Transcranial Doppler detects cerebral
      hypoperfusion in patients with hematoma. The excellent correlation of the average
      speed in the middle cerebral artery with the size of the lesion and the low
      correlation of the indices of pulsatility, which did not show interhemispherical
      asymmetry, suggest that the mechanisms of hipoperfusion are different from the
      intracranial hypertension.

PMID- 10951681
TI  - [Cerebral intraperenchymatous hematomas: surgical treatment not to start with].
AB  - INTRODUCTION: The surgical treatment of intraparenchymal hematomas is very
      controversial. To date, there has been no through analysis of the subject and
      neurological specialists need a broad study to indicate which patients should
      have surgical treatment and which is the surgical option which gives the best
      results with the least damage. DEVELOPMENT: In this paper, the author considers
      which patients should not have any operation, which should always be operated on
      and in which there is a relative indication for operation. The different
      techniques available, their advantages and disadvantages are briefly reviewed.
      CONCLUSIONS: In view of the results obtained to date, it is likely that in future
      the usual treatment for intraparenchymatous hematomas will be medical (not
      surgical) and aimed at the protection of surrounding tissue. When surgery is
      required, it should be as minimally invasive as possible.

PMID- 10951682
TI  - [Primary ventricular hemorrhage].
AB  - INTRODUCTION: Primary intraventricular hemorrhage is non-traumatic cerebral
      hemorrhage limited to the ventricular system which presents on rare occasions,
      forming 3% of the spontaneous cerebral hemorrhages. DEVELOPMENT: The diagnosis
      may be suspected when there is sudden onset of headache, nausea and vomiting with
      reduced level of consciousness. On examination there are signs of meningism,
      bilateral positive Babinski signs and absence of localizing neurological signs.
      However, cases of more subacute onset or with a normal state of consciousness are
      also seen. Therefore, in spite of clinical suspicion, diagnosis is made on
      cerebral computerized tomography. The aetiology is varied and it should be
      emphasized that vascular malformations cause 34% and in 21-47% no cause is found.
      Probably arterial hypertension is a major cause of primary intraventricular
      haemorrhage (38.5% in one series). Arteriography is necessary as well as
      computerized tomography for diagnosis of the aetiology. The prognosis is
      relatively good. The mortality is 29% and most survivors become asymptomatic or
      are left with only minor sequelae, often characterized by memory problems. In
      elderly patients there is a worse prognosis if there is an initial alteration in
      consciousness and if hydrocephaly occurs, but the prognosis does not appear to be
      affected by the volume of the hemorrhage. There is no specific treatment, but
      promising results have been obtained with intrathecal administration of
      fibrinolytic agents followed by external drainage.

PMID- 10951683
TI  - [Clinical aspects and prognostic factors of intracerebral hemorrhage].
AB  - INTRODUCTION: Intracerebral hemorrhage represents approximately 20% of all
      strokes. In spontaneous intracerebral hemorrhage the essential etiological factor
      is arterial hypertension, and the most frequent site the putamen and lobes of the
      cerebrum (lobar hematoma). The mortality is higher than in cerebral infarct,
      although the long-term prognosis is similar. DEVELOPMENT: We review the most
      relevant forms of presentation and clinical findings of intracerebral hemorrhage
      in adults, which show a combination of symptoms common to all types of hematoma
      and those symptoms which depend on their site. We also analyse the factors and
      studies which have sought to recognize variables predicting morbimortality.

PMID- 10951684
TI  - [Hyperpotassemia-related periodic paralysis: a rare complication of Addison's
      disease].

PMID- 10951685
TI  - [Chronic subdural hematoma due to rachianesthesia. A case report].

PMID- 10951686
TI  - The effect of welfare reform on SSA's disability programs: design of policy
      evaluation and early evidence.
AB  - During the past several years, the U.S. social safety net has gone through
      substantial changes involving an emphasis on personal responsibility and
      incentives, the shift of certain responsibilities to the states, and new limits
      on entitlements for benefits. Two pieces of recent legislation affected the
      Social Security Administration's (SSA's) disability programs. Section 105 of
      Public Law 104-121, enacted on March 29, 1996, mandated the removal of persons
      from the Supplemental Security Income (SSI) and Social Security Disability
      Insurance (DI) rolls for whom drug addiction and alcoholism (DA&A) were material
      to the determination of disability. It eliminated allowances on the basis of DA&A
      immediately and required the termination of benefits to all persons receiving
      benefits at the time of enactment. The other major piece of legislation was the
      Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996,
      which was later amended by the Balanced Budget Act (BBA) of 1997. PRWORA
      converted the Aid to Families with Dependent Children (AFDC) program from an open
      ended entitlement program into a block grant, Temporary Assistance for Needy
      Families (TANF), incorporating time limits on the receipt of benefits as well as
      strict work requirements. PRWORA also tightened child eligibility for SSI,
      narrowed eligibility for noncitizens, and reduced funding for food stamps. The
      BBA restored SSI eligibility for noncitizens receiving SSI prior to August 1996
      and for legal noncitizens residing in the United States prior to August 1996 who
      become disabled in the future. SSA designed three studies to assess the effects
      of this legislation. Two of the studies focused on direct effects on SSA's
      disabled beneficiary population, targeting drug addicts and alcoholics and SSI
      children. The third study focused on the indirect effects of PRWORA, particularly
      the replacement of AFDC with TANF, on SSA's programs. The three studies were tied
      together by a concern of the overall effects--direct or indirect--of the
      legislative changes on SSA's beneficiary populations and a host of interrelated
      evaluation issues. The key methodological challenge of these evaluations is the
      nonexperimental nature of the evidence. The legislative pieces mandating the
      changes designed to affect SSA's target populations were implemented nationally,
      without prior demonstration projects. Nonexperimental strategies, such as
      comparison group designs, must therefore be used to measure the effects of
      interest. Other challenges relate to the time frames. Since implementing the
      changes requires a certain amount of time, and outcomes are realized over a
      period of time after that, the information that can be made available to
      interested policymakers in the short run is inherently limited to descriptive
      data on the populations affected and to impressionistic evidence from case
      studies and process study analyses. The timing problem is particularly acute with
      respect to measuring the indirect effects of replacing AFDC with TANF, because
      the most important likely effects will occur over a period of several years, and
      this time frame may substantially vary across states as a result of the
      decentralized nature of TANF programs. Finally, the analyses that can be
      conducted are constrained by the lack of relevant data from existing surveys.
      Administrative record data alleviate the need for survey information for some
      purposes, but the lack of survey data still seriously constrains the analyses
      that can be done in the short term. Because of these methodological challenges,
      SSA designed an evaluation strategy that uses several methods and data sources,
      including quantitative analyses of data from surveys and administrative records
      (particularly data from the Survey of Income and Program Participation, or SIPP,
      matched to data from administrative records) and qualitative analyses through
      case studies. (ABSTRACT TRUNCATED)

PMID- 10951688
TI  - Participation in voluntary individual savings accounts: an analysis of IRAs,
      401(k)s, and the TSP.
AB  - New voluntary individual savings accounts have been proposed by some as a part
      of, or in addition to, Social Security. The success of these proposals would
      depend greatly on how many workers participate. This paper compares participation
      rates in three existing voluntary individual account-type plans--Individual
      Retirement Accounts (IRAs), 401(k)s, and the federal Thrift Savings Plan (TSP)-
      to clarify expectations about who might participate in a voluntary individual
      account system. It finds that participants in IRAs, 401(k)s, and the TSP tend to
      be disproportionately male, higher earners, older, full-time workers, and either
      white or nonblack minorities compared with the population at large. Differences
      in earnings explain much of the difference between participation rates of men and
      women, however, but less of the difference between participation rates of workers
      of different races. Whether participation in a new system of voluntary individual
      accounts would resemble participation in IRAs, 401(k)s, or the TSP would depend
      on a number of factors. For instance, the population covered by 401(k)s and the
      TSP is much smaller than that covered by Social Security. Average earnings are
      also higher among 401(k) and TSP participants than for workers covered by Social
      Security, which, based on these findings, suggests that participation rates could
      be lower in a universal system. Participation would also depend on many other
      factors, however, such as the extent of matching contributions or other financial
      incentives, the investment options available, and the amount of education
      provided to potential participants.

PMID- 10951687
TI  - The net effects of the Project NetWork return-to-work case management experiment
      on participant earnings, benefit receipt, and other outcomes.
AB  - The Social Security Administration (SSA) initiated Project NetWork in 1991 to
      test case management as a means of promoting employment among persons with
      disabilities. The demonstration, which targeted Social Security Disability
      Insurance (DI) beneficiaries and Supplemental Security Income (SSI) applicants
      and recipients, offered intensive outreach, work-incentive waivers, and case
      management/referral services. Participation in Project NetWork was voluntary.
      Volunteers were randomly assigned to the "treatment" group or the "control"
      group. Those assigned to the treatment group met individually with a case or
      referral manager who arranged for rehabilitation and employment services, helped
      clients develop an individual employment plan, and provided direct employment
      counseling services. Volunteers assigned to the control group could not receive
      services from Project NetWork but remained eligible for any employment assistance
      already available in their communities. For both treatment and control groups,
      the demonstration waived specific DI and SSI program rules considered to be work
      disincentives. The experimental impact study thus measures the incremental
      effects of case and referral management services. The eight demonstration sites
      were successful in implementing the experimental design roughly as planned.
      Project NetWork staff were able to recruit large numbers of participants and to
      provide rehabilitation and employment services on a substantial scale. Most of
      the sites easily reached their enrollment targets and were able to attract
      volunteers with demographic characteristics similar to those of the entire SSI
      and DI caseload and a broad range of moderate and severe disabilities. However,
      by many measures, volunteers were generally more "work-ready" than project
      eligible in the demonstration areas who did not volunteer to receive NetWork
      services. Project NetWork case management increased average annual earnings by
      $220 per year over the first 2 years following random assignment. This
      statistically significant impact, an approximate 11-percent increase in earnings,
      is based on administrative data on earnings. For about 70 percent of sample
      members, a third year of followup data was available. For this limited sample,
      the estimated effect of Project NetWork on annual earnings declined to roughly
      zero in the third followup year. The findings suggest that the increase in
      earnings may have been short-lived and may have disappeared by the time Project
      NetWork services ended. Project NetWork did not reduce reliance on SSI or DI
      benefits by statistically significant amounts over the 30-42 month followup
      period. The services provided by Project NetWork thus did not reduce overall SSI
      and DI caseloads or benefits by substantial amounts, especially given that only
      about 5 percent of the eligible caseload volunteered to participate in Project
      NetWork. Project NetWork produced modest net benefits to persons with
      disabilities and net costs to taxpayers. Persons with disabilities gained mainly
      because the increases in their earnings easily outweighed the small (if any)
      reduction in average SSI and DI benefits. For SSA and the federal government as a
      whole, the costs of Project NetWork were not sufficiently offset by increases in
      tax receipts resulting from increased earnings or reductions in average SSI and
      DI benefits. The modest net benefits of Project NetWork to persons with
      disabilities are encouraging. How such benefits of an experimental intervention
      should be weighed against costs of taxpayers depends on value judgments of
      policymakers. Because different case management projects involve different kinds
      of services, these results cannot be directly generalized to other case
      management interventions. They are nevertheless instructive for planning new
      initiatives. Combining case and referral management services with various other
      interventions, such as longer term financial support for work or altered provider
      incentives, could produc

PMID- 10951689
TI  - Attrition in the new beneficiary survey and followup, and its correlates.
AB  - Panel surveys interview the same individuals more than once over a period of
      time. Attrition from the survey occurs when those individuals die, refuse to be
      interviewed again, or, for some other reason, cannot be contacted. If the
      original sample was representative of a specific population, then survey analysis
      may provide misleading conclusions about changes in population characteristics
      over time if these individuals leave the sample in a nonrandom way. Therefore, it
      is important to identify the characteristics of individuals who leave the survey
      for various reasons. This article explores the extent of and reasons for
      attrition in the New Beneficiary Survey (NBS) between the first interview in 1982
      and the followup interview in 1991. Presented is a comparison of the
      characteristics of survivors (the reinterviewed sample) with attriters (those in
      the sample not reinterviewed) from the retired-worker and disabled-worker
      samples. The article explores a variety of potential determinants of attrition to
      the probability of attrition. These determinants are examined alone and in a
      multivariate framework. The NBS sample population is drawn from and linked to
      Social Security Administrative records, which have exact matched data on
      mortality as a cause of attrition. These data do not depend on survey-reported
      reasons for attrition; hence, it allows the examination of the differences in the
      patterns and predictors of attrition due to death and due to other reasons,
      primarily, the refusal to be interviewed. Attrition due to death must be
      identified precisely because misidentification of death as refusal to be
      interviewed may lead researchers to infer more selective attrition than might be
      the case. Different patterns of attrition are evident in the comparison of
      attrition levels and the determinants of attrition for the retired and disabled
      samples, both composed of persons with relatively high mortality risk. In
      particular, individuals' health, health insurance coverage, and level of
      education have different impacts on their likelihood of attrition. In general, it
      appears that refusal to be interviewed is more evenly spread across populations
      and characteristics than is death. The analysis shows that attrition due to death
      and attrition due to refusal are quite different processes, even though health
      conditions play a role in both processes. The results suggest that because
      attrition patterns (including death) may be quite different across population
      samples, sample-specific attrition patterns must be analyzed over the lifetime of
      any panel study. Long-term studies of panel attrition are necessary to provide
      researchers analyzing the data with information on potential biases due to
      nonrandom attrition.

PMID- 10951690
TI  - Summary of the 2000 annual Social Security and Medicare Trust Fund Reports.

PMID- 10951691
TI  - Increased efficiency of homologous recombination in ES cells by cleavage at both
      ends of homology in the targeting vector.

PMID- 10951692
TI  - Effect of flanking matrix attachment regions on the expression of microinjected
      transgenes during preimplantation development of mouse embryos.
AB  - The efficiency of transgenic animal production would increase if microinjected
      embryos with a successfully integrated transgene could be identified prior to
      transfer. It is possible to detect microinjected DNA in embryos. However, no
      reliable system is able to distinguish between transgenes merely present as
      extrachromosomal DNA and those that have been integrated into chromatin. The
      experiments reported here were designed to determine if the inclusion of matrix
      attachment regions (MARs) would enhance the efficiency of transgenic embryos
      identification using a selection scheme based on the expression of green
      fluorescent protein (GFP). Pronuclei of mouse embryos were microinjected with GFP
      reporter gene under the control of three different promoters and flanked or not
      by three different MAR elements. Transgene expression profiles were followed by
      direct visualization of GFP in cultured microinjected embryos. Embryos at
      different developmental stages were classified according to their GFP expression
      and groups with the same expression pattern were transferred into oviducts of
      pseudopregnant female mice. Fetuses were collected between days 12-15, and their
      genomic DNA was purified and analyzed to detect transgene integration. We did not
      find any statistically significant difference between the percentage of
      transgenic fetuses produced from GFP-positive or GFP-negative embryos transferred
      at 4-cell, morula, or blastocyst stage. However, when MAR elements were included
      in the construct, we found that GFP-positive embryos transferred at the 2-cell
      stage produced a significantly higher percentage of transgenic fetuses than GFP
      negative embryos, but MAR sequences did not completely eliminate false positives.

PMID- 10951693
TI  - The restoration of fertility in male sterile tobacco demonstrates that transgene
      silencing can be mediated by T-DNA that has no DNA homology to the silenced
      transgene.
AB  - Male sterile tobacco plants expressing a pathogenesis-related (PR) beta-1,3
      glucanase gene driven by the Arabidopsis thaliana A3 or A9 tapetum-specific
      promoter, were partially restored to fertility by retransformation with a range
      of pA9-driven sense and antisense PR glucanase fragments. The restored plants
      exhibited improved seed set. PR glucanase protein was undetectable in the anthers
      of these plants and there was an associated increase in microsporocyte callose,
      the structural target of the A3 and A9-driven PR glucanase. This phenotype was
      not solely dependent on interactions between sense and antisense PR glucanase
      transcripts since a pA9-driven restorer was also capable of down regulating a pA3
      GUS construct in the absence of extensive promoter, coding region, or terminator
      sequence homology. Since the A3 and A9 promoters have similar temporal and
      spatial expression patterns, it is possible that trans-acting factors common to
      both promoters become limiting in the PR glucanase double transformants resulting
      in improved levels of fertility. An alternative hypothesis is that additional
      sequences present in both the silencing and target T-DNAs can mediate the
      silencing of adjacent non-homologous transgenes.

PMID- 10951694
TI  - Transgenic Trifolium repens with foliage accumulating the high sulphur protein,
      sunflower seed albumin.
AB  - With the aim of increasing the rumen-protected level of the sulphur amino acids
      cysteine and methionine in Trifolium repens, we introduced the coding sequence of
      the sunflower seed albumin (SSA) into T. repens by Agrobacterium tumefaciens
      mediated transformation. The SSA gene was modified such that the protein would be
      localised to the endoplasmic reticulum (ER). Four different T-DNA constructions
      all containing the SSA gene driven by either the promoter of a gene encoding the
      small subunit of ribulose bisphosphate carboxylase (Rubisco) from Arabidopsis
      thaliana (Assu), the promoter of the gene encoding the small subunit of Rubisco
      of Medicago sativa (Lssu), or the Cauliflower Mosaic Virus 35S promoter
      (CaMV35S), were transferred to T. repens cv. Haifa. Transgenic T0-plants and
      inter-transgenic hybrids were analysed for the level of SSA accumulation in the
      leaves by western blotting. The highest observed level of SSA accumulation was
      0.1% of total extractable leaf protein. We observed that the promoter had a
      substantive effect on the level of SSA accumulation with Assu > CaMV35S > Lssu.
      Results from the inter-transgenic hybrids showed that the capacity to synthesise
      SSA was inherited. However the level of SSA accumulation in the leaves generally
      appears not to be additive with extra transgenic loci. During this work, we
      attempted to improve the efficiency of A. tumefaciens-mediated transformation of
      T. repens using the SAAT-method (Sonication Assisted Agrobacterium-mediated
      Transformation) on cotyledons of T. repens. T-DNA transfer was in general not
      enhanced by sonication compared to traditional A. tumefaciens-mediated
      transformation. Furthermore, Southern blot analyses of plants regenerated from
      the same cotyledon after A. tumefaciens treatment and under selection, indicated
      that multiple shoots were usually derived from the same transformation event. We
      concluded from these results that only one plant from each A. tumefaciens-treated
      cotyledon should be taken to avoid transgenic clones.

PMID- 10951695
TI  - Expression and immune recognition of SV40 Tag in transgenic mice that develop
      metastatic osteosarcomas.
AB  - Mature adult mice of the C57BL/6-TgN(Amy1TAg)501Knw transgenic mouse lineage,
      501, containing a liver alpha-amylase promoted-SV40 Tag hybrid gene, routinely
      develop SV40 Tag-induced metastatic osteosarcomas. This form of alpha-amylase was
      known to be expressed in the liver, salivary glands, pancreas, and fat. Cells in
      the normal rib adjacent to the periosteum also express alpha-amylase suggesting
      that transgene expression is correctly targeted to generate osteosarcomas. 501
      mice express SV40 Tag in the salivary glands but do not develop abnormalities in
      these organs by the time of their death from SV40-induced osteosarcomas. Mice of
      the C57BL/6 strain make a strong and effective anti-tumor immune response to SV40
      Tag immunization. However, immunization of 501 mice with SV40 Tag early in life
      does not alter or prevent SV40 Tag-induced osteosarcomagenesis. 501 mice mount a
      significantly less effective cytotoxic T-lymphocyte response following SV40 Tag
      immunization while 501 osteosarcoma-derived cells are fully susceptible to SV40
      Tag-specific T-cell lysis. This suggests that partial tolerance, not loss of
      antigen presentation by tumor cells, characterizes this mouse model of endogenous
      bone tumor development. To determine whether the immune recognition of endogenous
      SV40 Tag could influence tumorigenesis, the metastatic potential and time of
      death from tumor was investigated in CD4-null mutant 501 mice and beta-2
      microglobulin-null mutant 501 mice. The size and number of metastases in these
      strains and longevity of these strains varied. We suggest that components of both
      the innate and adaptive immune response control tumor appearance and progression.

PMID- 10951696
TI  - Oral immunization of mice with transgenic tomato fruit expressing respiratory
      syncytial virus-F protein induces a systemic immune response.
AB  - Respiratory syncytial virus (RSV) is one of the most important pathogens of
      infancy and early childhood. Here a fruit-based edible subunit vaccine against
      RSV was developed by expressing the RSV fusion (F) protein gene in transgenic
      tomato plants. The F-gene was expressed in ripening tomato fruit under the
      control of the fruit-specific E8 promoter. Oral immunization of mice with ripe
      transgenic tomato fruits led to the induction of both serum and mucosal RSV-F
      specific antibodies. The ratio of immunoglobulin subclasses produced in response
      to immunization suggested that a type 1 T-helper cell immune response was
      preferentially induced. Serum antibodies showed an increased titer when the
      immunized mice were exposed to inactivated RSV antigen.

PMID- 10951697
TI  - Enhanced levels of free and protein-bound threonine in transgenic alfalfa
      (Medicago sativa L.) expressing a bacterial feedback-insensitive aspartate kinase
      gene.
AB  - Threonine, lysine, methionine, and tryptophan are essential amino acids for
      humans and monogastric animals. Many of the commonly used diet formulations,
      particularly for pigs and poultry, contain limiting amounts of these amino acids.
      One approach for raising the level of essential amino acids is based on altering
      the regulation of their biosynthetic pathways in transgenic plants. Here we
      describe the first production of a transgenic forage plant, alfalfa (Medicago
      sativa L.) with modified regulation of the aspartate-family amino acid
      biosynthetic pathway. This was achieved by over-expressing the Escherichia coli
      feedback-insensitive aspartate kinase (AK) in transgenic plants. These plants
      showed enhanced levels of both free and protein-bound threonine. In many
      transgenic plants the rise in free threonine was accompanied by a significant
      reduction both in aspartate and in glutamate. Our data suggest that in alfalfa,
      AK might not be the only limiting factor for threonine biosynthesis, and that the
      free threonine pool in this plant limits its incorporation into plant proteins.

PMID- 10951698
TI  - Expression of a functional mouse-human chimeric anti-CD19 antibody in the milk of
      transgenic mice.
AB  - Human B cell lymphomas are suitable targets for immunotherapy. Clinical trials
      with mouse-human chimeric B cell-specific monoclonal antibodies (mAbs) have
      already shown promising results. However, limitations for their use in clinical
      trials can be the lack of sufficient amounts and high production costs.
      Expression of mAbs in the mammary gland of transgenic animals provides an
      economically advantageous possibility for production of sufficient quantities of
      a promising antibody for clinical trials and beyond. In this paper, we show the
      feasibility of this approach, by generating transgenic mice expressing mouse
      human chimeric anti-CD19 mAbs in their milk. Mouse anti-CD19 variable (V) region
      genes were combined with human IgG1 heavy (H) and kappa light (L) chain constant
      (C) region genes and fused to the bovine beta-lactoglobulin (BLG) promoter in two
      separate expression cassettes. Co-injection resulted in five transgenic lines. In
      one of these lines completely assembled chimeric mAbs were secreted into the
      milk, at an approximate level of 0.5 mg/ml. These mAbs were able to bind
      specifically to the CD19 surface antigen on human B cells.

PMID- 10951700
TI  - [Ethics of physician-patient relationship].
AB  - Ethical questions pertaining to the examination and treatment of patients have
      gained considerable importance during the last decades, also in psychiatry and
      psychotherapy. Interest in these questions, however, is moderate among students
      and beginning therapists. Ethical and legal problems often arise during practical
      work and are frequently solved without much consideration of the current ethical
      opinions and legal issues involved. This article tries to elaborate on the
      current ethical positions from an historical perspective and to come to a
      hierarchy of values, which could guide the therapeutic decisions. Nonmaleficence
      and autonomy are considered to be on top of that hierarchy, paternalism which was
      a guideline until the early sixties has lost its importance. The article
      discusses the consequences of this change of values in different practical
      fields, e.g. consent to long-term treatment with uncertain outcome,
      confidentiality in the face of dangers to third parties, suicidal patients.

PMID- 10951701
TI  - [Psychosomatic principles and therapy of chronic diseases].
AB  - Chronic illness is the main problem in modern medicine. The manner in which a
      person psychologically faces his chronic illnesses and attempts to deal with them
      represents his individual coping process. Psychosocial disturbances are more
      frequently present in the chronically ill than in the physically healthy and
      require application of step-wise psychotherapeutic treatment measures. Different
      problems and disturbances demand distinct therapeutic approaches. The therapeutic
      measures range from a comprehensive psychosomatic extensive treatment by a
      physician to professional psychotherapy.

PMID- 10951699
TI  - Role of the melanocortin-4 receptor in metabolic rate and food intake in mice.
AB  - We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of
      metabolic rate and food intake in mice. Intraperitoneal administration of the non
      selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases
      metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the
      effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to
      the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate
      control of both metabolic rate and food intake in mice. We infer that a role for
      MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food
      intake in wildtype mice seems limited.

PMID- 10951702
TI  - [Psychosomatics in gastroenterology].
AB  - Never before has the correlation between psychosocial factors and digestive
      diseases or disorders been studied more intensively than in the past decade. The
      following article will provide you with a survey of the major studies, functional
      gastrointestinal disorders, gastroesophageal reflux disease, peptic ulcer and
      chronic inflammatory bowel diseases taking into account psychosocial factors. The
      biopsychosocial model is a remarkable step forward in the process of learning
      more about these diseases, The integrated way of looking at biological,
      psychological and social factors has become an absolute must for those who want
      to fully understand the development and the severity of symptoms as well as
      diagnostics and therapy of these disorders.

PMID- 10951703
TI  - [Psychosomatics of the orofacial system].
AB  - The orofacial region, an area of human privacy of special personality relevance
      with overproportional cortical representation, appears to be particularly
      predisposed for a large number of different functional and somatoform disorders
      that affect both patients with and without teeth. In part there are marked
      differences as to their prevalence in male and female patients, with females
      being affected more often. These disorders lead in many cases to massive
      impainment of the patients' psycho-physical well-being, at times involving
      substantial consequential somatic damage. As a result of apparent shortcomings in
      primary care and preliminary diagnostics, many patients typically look back on
      long and complicated case histories with numerous negative examinations and
      futile attempts at somatic therapies and/or surgical interventions. The present
      paper aims, amongst others, at raising sensitivity for psychosomatic aspects in
      the dental medicine sector.

PMID- 10951704
TI  - [Various aspects of the gender difference--approached from a perspective of
      behavioral biology].
AB  - The various facets of human behaviour can only be reconciled in an empirically
      supported relationship from an ethological point of view when in addition to
      proximate causes (causation and ontogeny), ultimate causes (adaptation and
      phylogeny) are also considered. This will be demonstrated by the following
      examples: gender differences in behaviour, dominance, love and bonding. This
      comprehensive biological stance facilitates an understanding of one's own and the
      other sex.

PMID- 10951705
TI  - [Chemotherapy in metastatic or recurrent endometrial carcinoma].
AB  - Endometrial cancer is the fourth most common malignancy in women with an
      estimated 36,100 new cases diagnosed in the United States. The major treatment is
      surgical staging with hysterectomy, lymph node assessment and possible adjuvant
      irradiation. Systemic hormonal and chemotherapy has been reserved for women with
      disseminated primary disease or extrapelvic recurrence. Recent data showed that
      oral medroxyprogesterone, 200 mg/day, produced a 25% overall response for
      patients with well-differentiated histology and positive receptor status. In
      those patients especially if they are asymptomatic, endocrine therapy may be a
      reasonable initial approach. Patients with advanced or recurrent endometrial
      cancer should be considered for clinical trials using new agents or randomized
      trials designed to answer important questions. For patients not eligible for
      clinical trials, treatment with a platinum compound and paclitaxel or doxorubicin
      in combination should be considered.

PMID- 10951706
TI  - [Comparative studies on the biological significance of the marker for
      proliferation Ki-67-Antigen and PCNA in primary ovarian carcinoma].
AB  - OBJECTIVE: It was shown in experimental and clinical investigations, that the
      biological behavior of malignant tumors is reflected by their proliferative
      activity. PCNA and Ki-67-Antigen are two nuclear antigens and considered to
      represent important markers of proliferation. We investigated their proliferation
      index in primary ovarian carcinomas and correlated the results with tumor stage,
      grading, histological type and survival. MATERIAL AND METHODS: The expression of
      PCNA and Ki-67-Antigen was immunohistochemically evaluated using the monoclonal
      antibodies MIB-1 and PC 10 on formalin-fixed, paraffin-embedded tissue of 49
      patients. Statistical data were calculated by means of Fisher's Exact Test and
      Pearson's Chi 2 Test, survival was estimated by Kaplan Meier Curves. RESULTS:
      PCNA-expression was shown in all ovarian carcinomas and Ki-67-Antigen-expression
      was detected with one exception (98%) in all tumors, too. No correlation could be
      found between Ki-67-Antigen-expression and the prognostic factors mentioned
      above, whereas a high PCNA-expression was significantly correlated with the tumor
      grading (G3), (p < 0.05). Patients with ovarian carcinomas with high PCNA
      proliferation index showed the tendency of a shorter overall survival.
      DISCUSSION: Ki-67-Antigen and PCNA-expression could be detected in almost all
      primary ovarian carcinomas. PCNA compared to Ki-67-Antigen is considered to be
      more useful for the determination of the proliferative activity of ovarian
      carcinomas, although there was shown just a tendency of overall survival
      dependent on PCNA-expression, and there was a significant correlation only
      between PCNA-proliferation index and tumor grading.

PMID- 10951707
TI  - [Retrospective study of pelviscopic adhesiolysis for treatment of chronic lower
      abdominal pain (January 1996-December 1997)].
AB  - A report is given about 486 patients, who were operated because of suspicion of
      adhesion in 74 cases (15.2%), of an adnexal tumor 116 (23.9%), endometriosis 9
      (1.9%), infertility 24 (4.9%), irreversible contraception 42 (8.6%) or chronic
      abdominal pain in the lower abdomen 221 (45.5%). 89.1% of them suffered
      preoperatively of chronic abdominal pain. 350 (72%) patients had to be
      laparotomized once or several times. 326 women only had adhesions; adhesions and
      an adnexal tumor were found in 107 patients; 53 women had adhesions and
      endometriosis. Among the 326 women with adhesions only were about 45% with
      adhesions of first and just as many with second graduation, adhesions of third
      graduation were found in 10% of the patients. Adhesions of first graduation were
      solved completely in all cases, such of second graduation could be solved in 43%
      of cases completely and in 54% at least incompletely. Adhesions of third
      graduation were solved in most of the cases (74%) incompletely. 221 (67.8%) of
      the patients with adhesions only answered the questionnaires 8-10 months later.
      Two third of them were free from pain or stated a clear improvement. After
      complete adhesiolysis 70% of the women stated a positive result of operation, 57%
      after incomplete adhesiolysis.

PMID- 10951708
TI  - [Diagnosis and therapy of leg and pelvic deep vein thrombosis in pregnancy].
AB  - OBJECTIVE: To establish differences in the management of acute thrombosis in the
      deep venous system associated with pregnancy in patients undergoing thrombectomy
      and in patients receiving heparin therapy. MATERIALS AND METHODS: From 1984 to
      1995 the course of pregnancy was assessed retrospectively in 26 patients with
      acute deep vein thrombosis. Thirteen patients underwent thrombectomy with
      establishment of an arteriovenous fistula and 13 patients received conservative
      treatment with heparin therapy. In addition to the assessment of clinical
      symptoms, signs of thrombosis, diagnoses established with imaging techniques and
      of laboratory parameters, early complications and obstetric data obtained in
      surgically and conservatively treated patients were compared. RESULTS: The
      incidence of deep vein thrombosis in the 26 patients (median age 28 years) was
      0.21%. In 53.8% of the cases the occurrence of thrombosis was observed in the
      second trimester (median: 27.5 weeks of gestation). The presence of risk factors
      was demonstrated in 58% of cases. The most frequently reported symptoms were
      swelling of the affected leg (88.5%) and pain (61.5%). A marked predilection for
      the left leg was recorded in 88% of cases. In contrast to phlebography, twice the
      number of sonographic studies were performed. The comparison of both therapeutic
      regimes showed a three-fold increase in the rate of early complications in
      patients after thrombectomy. The rate of recurrent thrombosis in these patients
      was 58.3% compared to a recurrence rate of 15.4% in patients undergoing heparin
      therapy. CONCLUSIONS: Recurrent thrombosis and pulmonary embolism represent the
      most frequent complications associated with thrombosis in the deep venous system
      during pregnancy. Although currently there is a lack of conclusive data on the
      development of postthrombotic syndrome, heparin therapy appears to be associated
      with fewer maternal risks. Interdisciplinary cooperation is urgently needed.

PMID- 10951709
TI  - Pregnancy following operative and complementary treatment of thyroid cancer.
AB  - In 1974-1998, 18,602 patients were operated on due to goitre, including 16,575
      (89.1%) women and 2,027 (10.9%) men. Thyroid cancer was diagnosed in 975 (5.2%)
      by histopathologic examination. According to the WHO classification, there were
      449 (46.1%) patients with papillary carcinoma, 309 (31.7%) with follicular, 54
      (5.5%) with medullary, 106 (10.9%) with anaplastic, and 57 (5.8%) with other
      types of thyroid malignant neoplasms. Among them, there were 812 (83.3%) women
      and 163 (16.7%) men. Out of 758 patients with differentiated thyroid cancer, 545
      (71.8%) were treated complementarily with 131I. After surgery and complementary
      treatment, 23 (3%) thyroid cancer women (19 with papillary cancer and 4 with
      follicular one) became pregnant. Seven (30.5%) women were treated complementarily
      with 131I and levothyroxine, 3 (13.0%) with teleradiotherapy, 131I and
      levothyroxine, 1 (4.3%) with teleradiotherapy and thyroxine, and 12 (52.2%) only
      with levothyroxine. All women gave birth to healthy children. None of them
      developed recurrence before, during and after pregnancy. On the basis of the
      results obtained and the literature data one can conclude that it is possible to
      give birth to a healthy child after thyroidectomy and complementary treatment due
      to thyroid cancer, and that conception should occur after remission is confirmed
      and not earlier than 1 year after 131I treatment.

PMID- 10951710
TI  - A cure from the small cell neuroendocrine carcinoma of the uterine cervix
      following conventional surgery.
AB  - The small cell neuroendocrine carcinoma of the uterine cervix is a rare, but very
      aggressive neoplasm. Previous reports suggested that it had dismall prognosis if
      treated with conventional surgery and radiotherapy, even in early stage disease.
      We present the case of neuroendocrine cervical carcinoma that was cured from the
      disease following conventional surgery only.

PMID- 10951711
TI  - [Pronounced bilateral mammary hypertrophy as a rare manifestation of acute
      lymphatic leukemia].
AB  - A 33-year-old patient, hitherto healthy, has been admitted for clarification of
      bilateral mammary hypertrophy. In the course of the usual routine examination a
      lump of the size of a cherry was identified in the right breast. Within 6 weeks
      both breasts had become tight and grown symmetrically to three times their
      original size. A provisionary diagnosis of high malignant non-hodgkin lymphoma
      was made by multiple high speed needle biopsies and was later confirmed by a
      surgical tissue specimen of the right breast. For further classification a bone
      marrow biopsy was taken from the pelvic bone and an immature acute lymphoblastic
      leukemia (ALL), known as preB1-ALL, diagnosed. Sonographic examination, computer
      tomography of the thorax and mammographical findings, as well as symptoms,
      outcome and differential diagnosis of a proliferative lymphatic disease with
      first manifestation in both breasts are presented and discussed.

PMID- 10951712
TI  - Anaphylactic shock in response to wasp sting in pregnancy.
AB  - A case is described of stage 3 anaphylactic reaction in response to wasp sting in
      a woman in 27th week of gestation, followed by premature delivery in 35th week of
      gestation as the result of postanaphylactic reaction.

PMID- 10951713
TI  - Interventions during labor in relation to height in obese women.
AB  - The aim of the study was to investigate, whether height is a predictor of
      interventions during labor in obese women. Therefore the relationship between
      height and interventions during labor was investigated in 661 obese women
      delivering a single child in vertex presentation. Diabetic mothers were excluded.
      As a result there was a trend towards more medical inductions in tall women, but
      without reaching statistical significance. No other differences were found. We
      conclude, that short stature is not a major predictor of interventions during
      labor in Danish, obese women.

PMID- 10951714
TI  - [New findings on the role of Cooper ligament relevant to gynecologic surgery].

PMID- 10951715
TI  - Age variations in the properties of human tibial trabecular bone and cartilage.
AB  - Initiated and motivated by clinical and scientific problems such as age-related
      bone fracture, prosthetic loosening, bone remodeling, and degenerative bone
      diseases, much significant research on the properties of trabecular bone has been
      carried out over the last two decades. This work has mainly focused on the
      central vertebral trabecular bone, while little is known about age-related
      changes in the properties of human peripheral (tibial) trabecular bone. Knowledge
      of the properties of peripheral (tibial) trabecular bone is of major importance
      for the understanding of degenerative diseases such as osteoarthrosis and
      osteoporosis, and for the design, fixation and durability of total joint
      prosthesis. The specific aims of the present studies were: 1) to investigate
      normal age-related variations in the mechanical, physical/compositional, and
      structural properties of human tibial trabecular bone; and 2) to investigate the
      age-related and osteoarthrosis-related changes in the mechanical properties of
      the human tibial cartilage-bone complex; and 3) to evaluate mutual associations
      among various properties. Normal specimens from human autopsy proximal tibiae
      were used for investigation of age variations in the properties of trabecular
      bone and the cartilage-bone complex, and osteoarthrotic specimens were used for
      the investigation of changes in the mechanical properties of the cartilage-bone
      complex induced by this disease process. The mechanical properties and
      physical/compositional properties of trabecular bone were quantified by means of
      standard techniques, and trabecular bone structure was quantified by means of
      unbiased three-dimensional methods. The present study demonstrated that the
      mechanical properties, such as Young's modulus, ultimate stress, ultimate strain
      and failure energy, and the densities, such as apparent, apparent ash and
      collagen densities of human tibial trabecular bone have significant relationships
      with age. Tissue density and mineral concentration remain constant throughout
      life. Trabecular bone is tougher in the younger age, i.e. fracture requires more
      energy. Collagen density was the single best predictor of failure energy, and
      collagen concentration was the only predictor of ultimate strain. The decrease in
      mechanical properties of trabecular bone mainly is a consequence of the loss of
      trabecular bone substance. This study showed that the degree of anisotropy
      (preferential orientation of trabeculae), mean marrow space volume, and bone
      surface-to-volume ratio increased significantly with age. Bone volume fraction,
      mean trabecular volume, and bone surface density decreased significantly with
      age. Connectivity did not have a general relationship with age, yet a trend
      exists. Age-related changes in the microstructural properties had the same trends
      for both medial and lateral condyles of the tibia. The observed increase of
      anisotropy may be interpreted as the consequence of structural adaptation
      secondary to age-induced bone loss. The aging trabeculae align more strongly to
      the primary direction, which is parallel to the longitudinal loading axis of the
      tibia. The mechanical properties of the normal cartilage and bone vary with age
      and respond simultaneously to mechanical loading. Both cartilage and bone in
      early-stage OA are mechanically inferior to normal, and OA cartilage and bone
      have lost their unit function to mechanical loading.

PMID- 10951716
TI  - Bone mineral measurements at the knee using dual photon and dual energy X-ray
      absorptiometry. Methodological evaluation and clinical studies focusing on
      adaptive bone remodeling following lower extremity fracture, total knee
      arthroplasty, and partial versus total meniscectomy.

PMID- 10951717
TI  - A central theme of the Beijing +5 conference.

PMID- 10951718
TI  - Training aboriginal health care workers.

PMID- 10951719
TI  - Hepatitis B and medical students.

PMID- 10951720
TI  - Emergency contraception.

PMID- 10951721
TI  - St. John's wort and schizophrenia.

PMID- 10951722
TI  - Canadian normative data for the SF-36 health survey. Canadian Multicentre
      Osteoporosis Study Research Group.
AB  - BACKGROUND: The Medical Outcomes Study 36-item Short Form (SF-36) is a widely
      used measure of health-related quality of life. Normative data are the key to
      determining whether a group or an individual scores above or below the average
      for their country, age or sex. Published norms for the SF-36 exist for other
      countries but have not been previously published for Canada. METHODS: The
      Canadian Multicentre Osteoporosis Study is a prospective cohort study involving
      9423 randomly selected Canadian men and women aged 25 years or more living in the
      community. The sample was drawn within a 50-km radius of 9 Canadian cities, and
      the information collected included the SF-36 as a measure of health-related
      quality of life. This provided a unique opportunity to develop age- and sex
      adjusted normative data for the Canadian population. RESULTS: Canadian men scored
      substantially higher than women on all 8 domains and the 2 summary component
      scales of the SF-36. Canadians scored higher than their US counterparts on all SF
      36 domains and both summary component scales and scored higher than their UK
      counterparts on 4 domains, although many of the differences are not large.
      INTERPRETATION: The differences in the SF-36 scores between age groups, sexes and
      countries confirm that these Canadian norms are necessary for comparative
      purposes. The data will be useful for assessing the health status of the general
      population and of patient populations, and the effect of interventions on health
      related quality of life.

PMID- 10951723
TI  - Why are antibiotics prescribed for asymptomatic bacteriuria in institutionalized
      elderly people? A qualitative study of physicians' and nurses' perceptions.
AB  - BACKGROUND: Antibiotic therapy for asymptomatic bacteriuria in institutionalized
      elderly people has not been shown to be of benefit and may in fact be harmful;
      however, antibiotics are still frequently used to treat asymptomatic bacteriuria
      in this population. The aim of this study was to explore the perceptions,
      attitudes and opinions of physicians and nurses involved in the process of
      prescribing antibiotics for asymptomatic bacteriuria in institutionalized elderly
      people. METHODS: Focus groups were conducted among physicians and nurses who
      provide care to residents of long-term care facilities in Hamilton, Ont. A total
      of 22 physicians and 16 nurses participated. The focus group discussions were
      tape-recorded, and the transcripts of each session were analysed for issues and
      themes emerging from the text. Content analysis using an open analytic approach
      was used to explore and understand the experience of the focus group
      participants. The data from the text were then coded according to the relevant
      and emergent themes and issues. RESULTS: We observed that the ordering of urine
      cultures and the prescribing of antibiotics for residents with asymptomatic
      bacteriuria were influenced by a wide range of nonspecific symptoms or signs in
      residents. The physicians felt that the presence of these signs justified a
      decision to order antibiotics. Nurses played a central role in both the ordering
      of urine cultures and the decision to prescribe antibiotics through their
      awareness of changes in residents' status and communication of this to
      physicians. Education about asymptomatic bacteriuria was viewed as an important
      priority for both physicians and nurses. INTERPRETATION: The presence of non
      urinary symptoms and signs is an important factor in the prescription of
      antibiotics for asymptomatic bacteriuria in institutionalized elderly people.
      However, no evidence exists to support this reason for antibiotic treatment.
      Health care providers at long-term care facilities need more education about
      antibiotic use and asymptomatic bacteriuria.

PMID- 10951724
TI  - The natural history of smoking during pregnancy among women in Nova Scotia.

PMID- 10951725
TI  - The Canadian SF-36 health survey: normative data add to its value.

PMID- 10951726
TI  - Asymptomatic bacteriuria in institutionalized elderly people: evidence and
      practice.

PMID- 10951727
TI  - One solution to providing clinical coverage for pediatric inpatients.

PMID- 10951728
TI  - Smoking and women's health: opportunities to reduce the burden of smoking during
      pregnancy.

PMID- 10951729
TI  - Choosing a first-line drug in the management of elevated blood pressure: what is
      the evidence? 3: Angiotensin-converting-enzyme inhibitors.
AB  - Elevated blood pressure is associated with an increased risk of cardiovascular
      illness and death. Efforts to reduce that risk have led to recommendations for a
      wide array of nondrug and drug therapies. Choosing the optimal first-line drug
      for hypertensive patients should address a hierarchy of treatment goals: decrease
      in morbidity and mortality associated with hypertension, decrease in blood
      pressure and other surrogate markers, good tolerance, dosing convenience and low
      cost. This article examines the evidence for angiotensin-converting-enzyme (ACE)
      inhibitors as a class of first-line antihypertensive drugs in light of these
      treatment goals. Overall, the evidence does not support the use of ACE inhibitors
      as first-line drugs in the management of most patients with hypertension,
      although they have proven benefit as second-line drugs for the treatment of
      congestive heart failure and left ventricular dysfunction secondary to myocardial
      infarction.

PMID- 10951730
TI  - Providing after-hours on-call clinical coverage in academic health sciences
      centres: the Hospital for Sick Children experience.
AB  - An increasing number of admissions of patients requiring complex and acute care
      coupled with a decreasing number of pediatric postgraduate trainees has caused a
      shortage of house staff available to provide after-hours on-call coverage in the
      Department of Pediatrics at Toronto's Hospital for Sick Children. The Clinical
      Assistant program created to deal with this problem was short on staff, did not
      provide adequate continuity of care and was becoming increasingly unaffordable.
      The Clinical Departmental Fellowship program was created to address the problem
      of after-hours clinical coverage. The program is aimed at qualified pediatricians
      seeking additional clinical or research training in one of the subspecialty
      divisions in the Department of Pediatrics. We describe the hiring process, job
      description and evolution of the program since its inception in 1996. This
      program has been mutually advantageous for the individual fellows and their
      sponsoring divisions as well as the Department of Pediatrics and the Hospital for
      Sick Children. We recommend the introduction of similar programs to other
      academic medical departments facing staff shortages.

PMID- 10951732
TI  - Rate of HIV infection on rise among Ontario's gay men.

PMID- 10951731
TI  - The role of DNA amplification technology in the diagnosis of infectious diseases.
AB  - Nucleic acid amplification and detection methods developed in the past decade are
      useful for the diagnosis and management of a variety of infectious diseases. The
      most widely used of these methods is the polymerase chain reaction (PCR). PCR
      assays can detect rapidly and accurately the presence of fastidious and slow
      growing microorganisms, such as Chlamydia, mycoplasmas, mycobacteria,
      herpesviruses and enteroviruses, directly from clinical specimens. Commercial PCR
      assays for the diagnosis of tuberculosis and genital C. trachomatis infection are
      now routinely used in many diagnostic laboratories. Assays have also been
      developed that can detect antimicrobial resistance and are used to identify the
      cause of infection by organisms that cannot be cultivated. The value of viral
      load measurement by nucleic acid amplification in the management of patients with
      HIV infection or hepatitis C has also been well established. However, evaluations
      of this technology for rapid microbial diagnosis have generally been limited by
      small samples, and the cost of these assays may be as high as Can$125 per test.
      As nucleic acid amplification methods continue to evolve, their role in the
      diagnosis and management of patients with infectious diseases and their impact on
      clinical outcomes will become better defined.

PMID- 10951734
TI  - Letter from Durban.

PMID- 10951735
TI  - Number of health care workers lags behind population growth.

PMID- 10951736
TI  - Potential sperm donors should be tested for HPV.

PMID- 10951733
TI  - Are more online conferences on the way?

PMID- 10951737
TI  - Inhaled corticosteroids and COPD.

PMID- 10951738
TI  - ACE inhibitors and high-risk patients.

PMID- 10951739
TI  - Wife assault in Canada.

PMID- 10951740
TI  - Do more than discuss that unusual case. Write it up!

PMID- 10951741
TI  - Drugs that can worsen myasthenia gravis.

PMID- 10951742
TI  - Physician-organized healthcare system right on target.

PMID- 10951743
TI  - What price for your patient data? Medical record freeware may also become
      shareware.

PMID- 10951744
TI  - Is prolotherapy safe and effective for back pain?

PMID- 10951745
TI  - Epidemiology and diagnosis of tuberculosis. Recognition of at-risk patients is
      key to prompt detection.
AB  - The increasing incidence of TB and HIV infection and the emergence of drug
      resistance worldwide poses a major threat, particularly in developing nations. In
      an era with an increasing number of Americans living with HIV infection or with
      immunosuppression associated with chemotherapy or organ transplants, the
      possibility of primary M tuberculosis and of unusual clinical and radiographic
      presentations of reactivation disease is becoming more common. The primary care
      physician plays a crucial role in recognizing high-risk patients and initiating
      prompt isolation and evaluation.

PMID- 10951746
TI  - Tuberculosis and HIV infection. How to safely treat both disorders concurrently.
AB  - Progress has been made in screening, early recognition, prevention, and treatment
      of TB, but its coexistence with HIV infection continues to present a challenge.
      Healthcare professionals should be familiar with guidelines for treating HIV
      infected patients with TB while concurrently administering highly active
      antiretroviral therapy. Primary care physicians are encouraged to consult
      specialists who are familiar with treatment of patients with such coexisting
      disease. Whenever feasible, directly observed therapy should be instituted in all
      cases of TB to promote compliance and reduce the incidence of drug resistance and
      treatment failure.

PMID- 10951747
TI  - Management of tuberculosis. Choosing an effective regimen and ensuring
      compliance.
AB  - Management of active TB requires a team approach. All patients newly diagnosed
      with TB should be tested for HIV infection. Currently available anti-TB drug
      regimens are well tolerated and highly effective. Directly observed therapy has
      shown improved survival and decline in the rate of new cases of active TB. In
      suspected or proven drug-resistant TB, the regimen should be individualized in
      consultation with a specialist experienced in MDR TB. Primary care physicians
      play a pivotal role in reducing morbidity and emergence of drug resistance
      through early diagnosis and prompt initiation of an effective regimen under
      directly observed therapy.

PMID- 10951748
TI  - Prevention of tuberculosis. Vigilance and infection control strategies are
      mainstays of efforts.
AB  - Until a vaccine is available, efforts to control the spread of TB will continue
      to rely on the effective use of our currently available tools and the diligence
      of primary care physicians. Rapid diagnosis, directly observed therapy, public
      health and infection control measures, and appropriate preventive therapy remain
      the mainstays of TB control. Physicians in the primary care setting, particularly
      those serving long-term-care institutions or other high-risk populations, need to
      be keenly aware of the possibility of TB in their patient population and of the
      methods available in their community for preventing its spread.

PMID- 10951749
TI  - Combined classic and iatrogenic Kaposi's sarcoma. Corticosteroid withdrawal can
      result in remission.

PMID- 10951750
TI  - A triad of troubling findings. Plummer-Vinson syndrome.

PMID- 10951751
TI  - Anticoagulant use in nonvalvular atrial fibrillation. Determining risk and
      choosing the safest course.
AB  - Previous TIA or stroke, diabetes, advanced age, impaired left ventricular
      function, and a history of hypertension are strong risk factors in patients with
      nonvalvular AF. When none of these factors is present, aspirin in a dose of 325
      mg offers effective protection against future stroke. When any of these factors
      are present, warfarin adjusted to an INR of 2.0 to 3.0 offers greater protection
      against future stroke than aspirin alone or aspirin and fixed-dose warfarin (INR
      1.2-1.5). More data are needed before newer anticoagulants can be recommended for
      treatment.

PMID- 10951752
TI  - Screening for domestic violence. Identifying, assisting, and empowering adult
      victims of abuse.
AB  - Domestic violence involves the physical and/or psychological abuse of an intimate
      partner. Evidence indicates that almost one third of women treated in emergency
      departments have been in a violent intimate relationship within the previous
      year. For a variety of reasons, victims often do not choose to disclose that
      their injuries were a result of domestic violence unless they are asked directly
      by a physician in a safe, private setting. Constant vigilance is necessary to
      identify victims of such abuse who are afraid to disclose their often life
      threatening secret. Instituting a routine screening policy for all female
      patients over age 14 enables the identification of such victims and permits the
      assessment of immediate danger, after which appropriate referrals can be made and
      effective safety planning can be accomplished.

PMID- 10951753
TI  - New treatments for chronic edema in women?

PMID- 10951754
TI  - Dyspareunia in women. Breaking the silence is the first step toward treatment.
AB  - Dyspareunia is a heterogeneous disorder that has a number of potentially
      overlapping causes. It can be a source of great conflict and anxiety for many
      women. The primary care physician who takes the time to obtain a complete and
      careful sexual history and perform a comprehensive physical examination can help
      the majority of these patients. When dysfunction is complicated or refractory to
      treatment, gynecologic and psychosocial consultation may be necessary.

PMID- 10951755
TI  - Vasectomy. A safe, effective, economical means of sterilization.
AB  - Vasectomy is a common office procedure that is a permanent, safe, and effective
      form of birth control. It is less expensive and safer than tubal ligation.
      Physicians who wish to perform the procedure should be aware of the potential
      complications and explain them to the patient. Physicians also should perform the
      procedure often enough to have a low complication rate.

PMID- 10951756
TI  - Tuberculosis.

PMID- 10951758
TI  - [Health care costs at the end of the last century].

PMID- 10951757
TI  - [Surgery of the greater omentum--today and in the past].

PMID- 10951759
TI  - [Surgical treatment of toxic adenoma].
AB  - In the period ranging from 1985. to 1994. a total number of 86 patients have been
      treated for toxic adenoma (TA). Hyperthyroidism was more often present in males
      (70.83% versus 51.61%) and in enlarged adenomas (more then 2 cm in diameter).
      Pathohistologic type of adenoma influenced degenerative changes. Three carcinoma
      have been observed, two papillary and one follicular. Surgical treatment is the
      method of choice. Complications are rare (3.49%) and mild.

PMID- 10951760
TI  - [Angiographic analysis of the tensor fascia lata vascularized flap].
AB  - Vascularisation of the flap of tensor fasciae latae originates from the ascending
      branch of the lateral circumflex femoral artery which enters through the medial
      side of fascia lata tensor as a dominant branch. Knowing the vascular and
      characteristics of a vascular peduncle is of great importance while taking the
      flap, so knowing the site of the source of lateral circumflex femoral artery
      diameter at the source, the number of the terminal branches and the number of
      ascending branch anastomoses of lateral circumflex femoral artery are the basic
      significance for successful taking of the flap and its clinical application. Our
      investigations were done on clinical material, and the study was based on
      investigations of angiographies of the femoral artery. Measuring the diameter in
      the source of ascending branch we found that it was 33 mm while the diameter in
      the bifurcation of the terminal branches of ascending branch was 2.41 mm in
      average. The length of vascular peduncle of ascending branch was 68.88 mm in
      average. Vascular peduncle of the flap of tensor fasciae latae has appropriate
      length and diameter for microvascular anastomosis.

PMID- 10951761
TI  - [Ruptured abdominal aortic aneurysms].
AB  - Eighty two aortic replacements of ruptured abdominal aortic aneurysms have been
      performed during the last 6 years. There were 72 male and 10 female patients, and
      the average age was 71.33 years. Hemorrhagic shock on the admission was observed
      in 45 patients, and 13 have been operated urgently without any diagnostic
      procedures. The transperitoneal approach have been used for the operation. Two
      aorto duodenal and one aorto caval fistulas, have been found. Only exploration
      (three patients died immediately after laparotomy and 6 after cross clamping) has
      been done in 9 cases, and the aortic replacement in 70 cases (27 with tubular,
      and 43 with bifurcated graft). In 3 cases and axillobifemoral bypass had to be
      done. During the operation eleven patients died, and 30 in postoperative period,
      during the period between one and 40 days. Total intrahospital mortality rate was
      50%, compared with 3.5% for 250 electively operated patients with abdominal
      aortic aneurysms in same period. In postoperative period the most important cause
      of death was multiple organs failures. Statistically significant greater
      mortality rate (p > 0.01%) was found in cases of late operative treatment,
      hemorrhagic shock, intra-operational bleeding, ruptured front wall, suprarenal
      cross clamping and in patients older than 75 year. In complicated cases such as
      juxtarenal aneurysm, 3 sutures parachute technique for proximal anastomosis, a
      temporary transection of the left renal vein, and intraaortal balloon occlusive
      catheter for proximal bleeding control are recommended.

PMID- 10951762
TI  - [Vaginoplasty in male to female sex change operations].
AB  - Vaginoplasty presents the main procedure in one-stage male to female sex
      reassignment surgery. Our new vagina consist of two parts: a long vascularized
      urethral flap and a pedicled island tube skin flap serrated from the penile skin.
      The urethral segment of the vagina plays a major role, giving the vagina depth,
      width and providing moisture. In the period from January 1989 to August 1995, 89
      patients aged 18 to 56 years underwent surgery. The follow-up ranged from 3
      months to 6 years (mean 4.1 years). Satisfactory cosmetic and functional results
      were obtained in 86% of cases.

PMID- 10951763
TI  - [Paraesophageal hiatal hernia of the diaphragm].
AB  - Paraesophageal hernia (type II hiatal hernia) accounts for less than 5-10% of all
      herniation through the esophageal hiatus. Anatomically, it is distinguished from
      the more common sliding variety (type I hiatal hernia) by the position of the
      gastroesophageal junction. The management of paraesophageal hiatal hernia is
      influenced by the tendency of the herniated stomach to develop volvulus, which
      potentiates life-threatening complications that include complete gastric
      obstruction, bleeding, infarction and perforation. In a cases with
      gastroesophageal reflux one of the antireflux procedures had to be done. In the
      Institute of Digestive Diseases, in the 16 years period from 1980-1996, 37
      patients had treated of paraesophageal hernia. Authors discuss their management
      strategies, especially the using of antireflux procedures.

PMID- 10951764
TI  - [Malignant disease of the appendix].
AB  - The authors shows case report 81 old patient, underwent surgical treatment on
      Surgical Clinic KBC DR Dragisa Misovic because of malignant appendix. Primary
      symptoms of illness was acute abdomen. Histology confirm nature of illness. The
      authors discusses about different types of malignant appendix and ways of their
      treatment, and propose operative procedures which are need to be done in these
      cases.

PMID- 10951765
TI  - [Diverticulum of the stomach].
AB  - Gastric diverticula are very rare and usually asymptomatic diseases. Clinical
      symptoms may include haemorrhage, mild discomfort and pain in upper abdomen. They
      are most frequently diagnosed incidentally during X-Ray examinations. In
      symptomatic diverticulum of gastric fundus was diagnosed roentgenographically and
      endoscopically and was successfully cured surgically.

PMID- 10951766
TI  - [Hemihepatectomy in hepatoblastoma in an infant].
AB  - Our patient was the first registered and operated case caused by multifocal
      hepatoblastoma, located in the right lobe. The decision to operate, our young
      patient, was a certain challenge, considering local diagnostic and surgical
      possibilities. The results of the two-years follow up (based on every three
      months check-ups), level of the alpha-fetoprotein, showed very fast normal level,
      even it were no so high preoperatively. We also did not have any sign of local
      reoccurrence or long distance metastasis. Chemotherapy does not have to be
      necessary prerequisite of extension surviving, specially in the fist phase, when
      the process is located in the lobe or segment, also resectable and without any
      metastasis.

PMID- 10951767
TI  - Isolated hydatid cyst of the adrenal gland.
AB  - Hydatide disease of the adrenal gland is extremely rare, even in disseminated
      disease. Isolated cyst of the gland is even more rare. Only 9 of such cases seem
      to have been described so far. We present a 49 year old woman in whom a hydatide
      cyst of the right gland was found during the investigation for the dull pain in
      the area. She was successfully operated. Hydatide etiology was confirmed at
      operation and by histology. She had an uneventful recovery. The preoperative pain
      disappeared postoperatively.

PMID- 10951768
TI  - [Overview of the surgical importance of variations in the hepatic artery].
AB  - Hepatobiliary and gastric surgery greatly depend upon knowledge and recognition
      of origin, relations and course of the hepatic artery. This paper presents the
      main variants of the arterial vessels in the hepatoduodenal ligament, with a
      concise review on their clinical relevance. Special attention was drawn to the
      aberrant hepatic arteries, which are found in nearly half of the cases, and to
      the macro- and microvasculature of the common bile duct.

PMID- 10951770
TI  - [Quality of life in patients with a modified Mainz-pouch II urinary diversion].
AB  - The type of urinary derivation after radical cystectomy due to urinary bladder
      carcinoma does not influence survival substantially, but it may influence the
      quality of life of the patients very much. One of modifications of classical
      ureterosigmoidostomy that has been focused by urologist in recent years in the
      sigma rectum pouch (Mainy pouch II), for its substantially improved aspects of
      quality of life and earlier occupational rehabilitation of these patients. In the
      period August 1994 through March 1998 we made Meinz pouch II (the modification
      implies fixation of the pouch to the parietal peritoneum and implantation of the
      ureter into the pouch as suggested by Camey-Le-Duc). This surgical technique is
      associated with lots of advantages as the continent form of urinary derivation,
      and as a fairly simple surgical technique it is an improvement in this type of
      surgery. Intactness of the abdominal wall (no urostoma), frequency of
      defecation/urination in 3-4 hr intervals during the day and 4-5 hours during the
      night, absolutely volitonal control of these functions, rapid postoperative
      recovery with stabilization of renal function parameters, low percentage of
      ascending infections, higher degree of occupational rehabilitation, i.e. lower
      incidence of disability and good psychosocial status are all advantages of this
      method in the light of the quality of life of these otherwise very difficult
      patients.

PMID- 10951769
TI  - [Surgical treatment and quality of life in patients with carcinoma of the penis].
AB  - Penile carcinoma is a rare disease with the annual incidence of 1-2 cases per
      100,000 men. About 95% of all penile malignancies are squamous cell carcinoma. At
      the Clinic of Urology in the period 1988-1998 we treated 58 patients with penile
      carcinoma. Nine of these (15.5%) were subjected to total penectomy due to the
      extent of the lesion, while partial amputation of the penis was performed in
      84.5% (49 cases). The aim of the therapy was to completely remove the primary
      lesion with adequate margins. Postoperative follow-up comprised, among other
      things, evaluation of the quality of life as reflected in pain, sexuality and
      emotional distress. Quality of life of patients subjected to partial penectomy
      where no cases of relapse were recorded, was satisfactory, while in cases of
      total penectomy about 24% (14 patients) suffered marked emotional distress
      induced by the loss of the mark of male sexuality and sexual impotence. In the
      light of the prominent problems related to the quality of life induced by severe
      psychological influence of penis amputation, local excision, Mohs's operation and
      laser therapy are increasingly used in the treatment of penile carcinoma.

PMID- 10951771
TI  - [Quality of life in patients with renal carcinoma].
AB  - First line treatment of renal cell carcinoma (RCC) is radical nephrectomy. In
      patients with metastasis or with local recurrence adjuvant immunohaemiotherapy is
      necessary. Interferon alpha is used with or without Interleukin 2 in combination
      with cytostatics. Immunotherapy induces some adverse effects which might
      compromise the treatment. The aim of this pilot study was to asses the effect of
      interferon on the quality of life in patients with RCC previously treated with
      radical nephrectomy. The originally made questionnaire was used to measure the
      impact of the treatment on quality of life of 15 patients. It was that Interferon
      did not alter significantly the quality of life in examined patients.

PMID- 10951772
TI  - [The Camey enteroplasty after radical cystoprostatectomy: complications, results,
      quality of life].
AB  - Removal of the urinary bladder-cystectomy--imposes the problem of urine
      derivation. The most sophisticated forms of urinary derivation imply those where
      the continent urinary reservoir is anastomosed to the urethra. One of these is
      Cameys enteroplasty. In our hospital this technique was applied on 52 patients.
      Postoperative complications and obtained results suggest that this form of
      urinary derivation is an important step nforward not only to incontinent forms of
      derivation, but to non-orthotopic continent urinary derivations, as well. All
      patients in our series were very successful in reintegration into the normal
      life, i.e. they were able to achieve a high a high quality of life after
      otherwise mutilating surgical procedure.

PMID- 10951773
TI  - [Quality of life in patients with tumors of the upper urothelium and indications
      for conservative surgery].
AB  - The motives for performing conservation surgery in tumors of the upper urinary
      tract are progressive renal failure associated with those tumors, frequent
      bilateral tumors, and tumors on solitary kidney, which does not always comply
      with the patho-anatomic characteristics of the tumor and possibilities of this
      type of surgery. The aim of the study was to separate the real indications for
      the application of this therapy, independently of the expected quality of life
      after the operation. Out of 682 patients with upper urothelial tumor conservation
      surgery was performed in 161 patients. The indications were characterized as
      "real", oncologic in 121 patient, and in 40 patients (25%) the main reason was
      preservation of quality of life. During the five-year follow-up period recurrence
      developed in 17% of patients in the group with oncologic indications, "real"
      indications, and in as much as 40% of patients from the group in with the main
      reason was preservation of quality of life. Thus, the oncologic indications must
      be primary in reaching the decision for conservation surgery in tumors of the
      upper urinary tract, and the quality of life should be an additional motive for
      this therapy.

PMID- 10951774
TI  - [Quality of life and anesthesia in extensive urologic surgery].
AB  - Urologic patients have overlap disturbances in many organ systems, specially in
      urinary system with cardiovascular and respiratory system. During extensive
      urologic operations we perform general anaesthesia in most cases. General
      anaesthesia provide organ vital function under best control. Patient with severe
      respiratory disease undergoing surgery in regional anaesthesia (spinal or
      epidural with or without epidural catheter, or in combined spinal-epidural
      anaesthesia). We perform all type of anaesthesia at Institute for Urology and
      Nephrology of Clinical Centre of Serbia.

PMID- 10951775
TI  - [Quality of life after retroperitoneal lymphadenectomy in low clinical stages of
      nonseminomatous testicular tumors].
AB  - The surgical complications and quality of life in 139 patients who underwent
      primary retroperitoneal lymphadenectomy for clinical stage A and B1/B2 non
      seminomatous testicular tumors during the period ranging from 1975 to 1997 were
      reviewed. Bilateral retroperitoneal lymphadenectomy was performed in 26 patients,
      and modified unilateral in 113 patients. There were 23 complications in 36
      patients (16.5%) and only 1 case of surgery-related mortality. There were 28
      early complications and 8 late complications. The most frequent minor
      complication encountered was superficial wound infection, whereas many of the
      major complications were related to small-bowel obstruction and atelectasis. The
      complication rate was lower in patients who underwent modified unilateral
      procedures than in those who had bilateral dissections (76.9:14.5%). The most
      prominent element of quality of life is preservation of normal ejaculation
      (69.8%), significantly better preserved in unilateral dissection (80.5:23.1%).
      This study reinforces the conclusion that primary unilateral retroperitoneal
      lymphadenectomy is and operation yielding minimal morbidity, excellent quality of
      life and no long-standing effects.

PMID- 10951776
TI  - [Quality of life after kidney transplantation].
AB  - 316 kidney graft recipients responded to the questionnaire. The questionnaire
      concerned general, physical and mental life quality as well as sexual capacity,
      the attitude towards graft and donor and immunosuppressive side effects. The
      questionnaire had a rating scale from 0 to 4. The ratings were correlated with
      clinical data (creatinine, hemoglobins levels, duration after transplantation) by
      simple bivariate correlation coefficient (r) was estimated. Statistical
      significance (P < 0.05) was defined as r > 0.11 for n = 316. A general
      improvement of life quality after renal transplantation was noted by 87.5% of
      patients. This statement did not correlated to time after transplantation, serum
      creatinine levels or hemoglobin levels. 40.8% of patients evaluated their
      physical conditions as good, these data again did not correlate to hemoglobin
      levels or kidney function (expressed as serum creatinine). 73.1% regarded their
      mental condition as excellent and only 4% as poor. Again, mental condition did
      not correlate to hemoglobin levels or renal function. Sexual function was
      assessed to be good or excellent by 48% of patients. In contrast to these
      positive results, a minority of 14.5% of patients participated in sporting
      activities on a regular full basis and only 37.5% of all patients believed them
      selves to be capable of performing a full time job. Only 12.9% suffered from drug
      related side effects. Transplantation itself posed no emotional problem for the
      recipients. Only 2.2% felt unpleasant about carrying a foreign organ and only
      17.4% reflected on their donor.

PMID- 10951777
TI  - [Uretero-cutaneoustomy--indications and quality of life].
AB  - Ureterocutaneostomy, the anastomosis of the ureter to the skin, represents the
      most simple supravesical urinary derivation. It can be performed as unilateral,
      bilateral, bilateral with one orifice, or rarely as transuretero
      ureterocutaneostomy. In period 1993-1998 on the Clinic of Urology, Clinical
      Center of Serbia, ureterocutaneostomy was performed in 155 patients as definitive
      type of urinary derivation. The most frequent indication for this type of
      derivation was the bladder tumor (130 out of 155 pts.). The rest of 25 pts. had
      carcinoma of vaginal portion of uterus, vesico-vaginal fistula (most frequently
      after irradiation), high ureteric lesions bladder neurogenic disfunction or rare
      bladder diseases. Having in mind short period of follow up two major
      complications were noticed: stenosis of uretero-cutaneostomy and retraction of
      anastomosis with consecutive formation of subcutaneous urinoma and abscesses
      formation. Although rarely used as definitive type of urinary anastomosis,
      ureterocutaneostomy has its place in wide spectrum of urinary derivations, since
      it is the only way to help those patients that have no other option of urinary
      derivation that might provide better way of social and professional
      rehabilitation.

PMID- 10951778
TI  - [Ileal conduit--quality of life].
AB  - Removal of the urinary bladder--cystectomy--imposes the problem of urine
      derivation. The most sophisticated forms of urinary derivation imply those where
      the continent urinary reservoir is anastomosed to the urethra. One of these is
      Came's enteroplasty. In our hospital this technique was applied on 52 patients.
      Postoperative complications and obtained results suggest that this form of
      urinary derivation is an important step forward not only to incontinent forms of
      derivation, but to non-orthotopic continent urinary derivations, as well. All
      patients in our series were very successful in reintegration into the normal
      life, i.e. they were able to achieve a high quality of life after otherwise
      mutilating surgical procedure.

PMID- 10951779
TI  - [Rectal carcinoma--therapeutic dilemmas and possibilities].

PMID- 10951780
TI  - [Endorectal ultrasonography].
AB  - Endorectal ultrasonography is a diagnostic technique that can provide clear image
      of the rectal wall and the pararectal tissues. The examination is rapid, well
      tolerated by the patient and accurate. Indications for this investigation include
      preoperative staging of rectal tumors, surveillance of rectal cancer, and
      evaluation of pararectal masses. Endoanal ultrasonography provides an image of
      the anal sphincter muscles and the perianal tissues. Indications for this
      examination include the evaluation of incontinence, anal fistulas, anal carcinoma
      and anal pain. A detailed discussion of the image interpretation follows.

PMID- 10951781
TI  - [Epidemiologic status of colorectal carcinoma in Yugoslavia].

PMID- 10951782
TI  - Rectal cancer--from genetics to the therapy.
AB  - Cancer of the colon and rectum is major cause of cancer-associated morbidity and
      mortality. Globally, it is the third most common cancer in males and fourth most
      common in females. Colorectal cancer is primarily a genetic disease with lesions
      being either somatically induced by environmental agents or inherited through the
      germline. Familial adenomatous polyposis and hereditary non-polyposis colorectal
      cancer are the main types of inherited colorectal cancer. Sporadic colorectal
      cancer is though to involve several genes in a multistep pathway. Colorectal
      cancer occurs as a result of a series of genetic alterations in normal tissue
      that lead to disorganization in the molecular mechanisms that control growth.
      Most of the evidence incriminating diets as a major factor in the genesis of
      colorectal cancer. Case control studies and complex statistical analyses
      implicate both causative and protective dietary factors. The aim of screening is
      to detect neoplasia of the colon and rectum before it reaches an advanced stage,
      survival being directly related to the stage at presentation. The most sensitive
      evaluation of the whole colon is by colonoscopy. The way forward continues to
      rest with research into more sensitive occult fecal blood tests, more cost
      effective endoscopic protocols and greater knowledge of the biological factors
      triggering dysplastic changes in large bowel mucosa.

PMID- 10951783
TI  - [Ulcerative colitis and familial adenomatous polyposis--risk factors in the
      development of colorectal carcinoma].

PMID- 10951784
TI  - Monoclonal antibodies in the diagnosis and treatment of the colorectal cancer.

PMID- 10951785
TI  - Total mesorectal excision.

PMID- 10951786
TI  - [Mechanical anterior low anastomosis of the rectum in carcinoma-- results and
      survival rate].

PMID- 10951787
TI  - Abdomiosacral resection of recurrent rectal cancer in the sacrum.
AB  - Isolated manifestation of recurrent rectal cancer in the pelvis after primary
      radical resection occurs in 7 to 33% and frequently causes severe sacral pain.
      Sacral recurrence gravely impairs the quality of life as well as life expectancy.
      Irradiation offers a means of palliation. However, even if radiation is effectful
      it only provides symptomatic recurrent tumors frequently remain radioresistant
      1.4. Only portal sacral resection potentially provides curative treatment if the
      Recurrent tumor is limited to the sacrum. Without surgical therapy the life
      expectancy of patients with local recurrence of rectal cancer is about 7 months.

PMID- 10951788
TI  - Rectal cancer with an extension outside mesorectum but curable.

PMID- 10951789
TI  - [Surgical treatment of liver metastases of colorectal carcinoma].
AB  - Colorectal carcinoma metastasizes into the liver, but liver-only metastases are
      infrequent. Liver-only metastases are seen mainly from colorectal carcinoma. This
      is the only metastatic disease where treatment aimed only or mainly at the liver
      metastases is employed with curative intent. If liver resection for colorectal
      metastases is done by an experienced team, adhering to predefined indications,
      five year survival ranges from 30-40%, operative mortality is 3-5% and the
      postoperative morbidity is acceptable. New diagnostic techniques have been
      introduced and indications for liver resection extended. This paper presents the
      current limitations and possibilities for the surgical management of colorectal
      metastases in the liver.

PMID- 10951790
TI  - [New prognostic parameters and categories of colorectal carcinoma--correlation
      with standards].
AB  - The proper staging of colorectal cancer was discussed with emphasis on the most
      relevant pathological parameters. Standard staging classifications i.e. Dukes',
      Astler-Coller's and international TNM classifications are defined by a few basic
      parameters, namely local invasion and lymph node metastasis, along with the
      histological grade of differentiation. Advances in diagnosis and treatment and
      modern aspects of tumor biology introduced other prognostic factors regarding
      proliferative activity of tumor, its local and systemic effects, host defense
      mechanisms and metastatic potential. Independent prognostic significance was
      shown and/or new criteria recommended for: resection margin and peritoneal
      involvement, vascular invasion, tumoral mucin production activity, presence of
      extranodal (micro) metastasis, extent of presented (extra) mural tumor spread,
      peritumoral lymphocytic infiltration, character of tumoral invasive margin and
      presence of peritumoral Crohn's-like lymphoid reaction. The se pathological
      parameters, discussed in detail, were partly contained in new revision of TNM or
      other classifications, not widely accepted, such as Jass', Japanese JSCCR,
      British UKCCCR classification, or new prognostic categories proposed by Harrison
      and coworkers. Our own first experiences and primary results showed variable
      agreement most of the mentioned parameters with special respect to
      reproducibility of Harrison's new prognostic categories. Many newly developed
      methods and novel tumor markers with some predictive values on clinical outcome
      are recently recognized, still uncertain for routine clinical usage. We reviewed
      in brief most important and/or most studied pathobiological predictors, such as:
      DNA ploidy, markers of proliferative activity, expression of tumor-specific and
      tumor-associated antigens or receptors. Among many of hereditary and genetic
      markers we stressed the importance of RER phenotype, mutations of tumor
      suppressor genes and some oncogenes, allelic loss of 18q, 17p and other
      chromosomal alleles as prognostic and screening tools or therapeutic targets. In
      conclusion, more new insights in carcinogenesis and new therapeutic agents will
      require new classification systems, never considered as definitive.

PMID- 10951791
TI  - Preoperative accelerated hypoxiradiotherapy of rectal cancer. Preliminary
      results.

PMID- 10951793
TI  - [Dr. Toma Leko in Serbian medicine].

PMID- 10951792
TI  - [Dynamic graciloplasty in the treatment of severe fecal incontinence--2 case
      reports].
AB  - Severe fecal incontinence is a serious problem not only for the patient whose
      quality of life is diminished, but also for the surgeon, who sometimes has
      difficulties how to manage all the aspects of this complicated condition.
      Conservative treatment is often ineffective, while operative sphincter repair is
      feasible only when anal sphincter is relatively functional and conserved. Dynamic
      graciloplasty is a method where functional anal neosphincter is constructed by
      transposing m. gracilis and wrapping it around the anal canal with subsequent
      implantation of electric neurostimulator and electrodes. Relatively good
      continence can be achieved with this technique, especially in-patients where all
      other therapeutic options failed. We present two patients, 25 and 21 years old,
      operated on our department, both suffered from severe fecal incontinence from the
      time they were born. They were interviewed, underwent a physical examination and
      evaluated by anal manometry, defecography and electromyography. Severe fecal
      incontinence was revealed (18 and 20, according to the Continence grading scale).
      In both cases, Gamma graciloplasty was performed. At first patient, implantation
      of the neurostimulator was performed 8 months after graciloplasty, while in
      second case, both graciloplasty and implantation of the electrodes with
      neurostimulator were performed at the same time. Postoperative recovery was
      uneventful in both cases. There was minor infection of the perineal wound in one
      patient. Electrostimulation training program was started on 9th postoperative day
      in both cases. Functional results were revealed by questionnaire and anal
      manometry. The quality of life was significantly improved in both cases, with
      good continence and psychological recovery. Anal manometry revealed increased
      anal contraction pressure comparing with preoperative basal and squeeze
      pressures. Dynamic graciloplasty is a relatively new; high specialized method in
      treatment of intractable, fecal incontinence. It is safe and reliable procedure
      in hands of an well-experienced surgeon, if well indicated and performed.

PMID- 10951794
TI  - [Peritoneal sepsis in elective and colorectal surgery].

PMID- 10951795
TI  - [A scoring system for polytrauma patients].
AB  - The paper presents a review study on score systems in current emergency surgery
      including its classification, application and value, based on the experiences of
      other authors, the paper suggests application of score systems in different
      phases of polytraumatized patients treatment (in prehospital, as well as in early
      and late phases of the inpatient period). The paper also points out certain
      objective difficulties in everyday scoring of patients at the Department of the
      Emergency Surgery (daily engagement, computer center, etc.). As a conclusion, the
      authors present their opinion indicating that in absence of introduction of these
      systems into the practice, the approach to a polytraumatized patient cannot be
      adequate.

PMID- 10951796
TI  - [Necrosis of the omental flap].
AB  - The aim of this research is to review the frequency of the omental flap necrosis
      comparing the vascularized omental flaps based on the left or right
      gastroepiploic vessels. The first 100 patients, with injuries of spinal cord on
      different levels, are included in this prospective clinical study with follow-up
      from 12 to 24 months. The special surgical technique was used for preparation of
      omental pedicled graft, for its lengthening and transposition to the level of the
      spinal cord injury and direct and indirect signs of the omental flap necrosis
      were studied. In our patients there was no necrosis of the omental grafts based
      on the left gastroepiploic artery. The insufficiency of the left gastroepiploic
      artery was not present in any patient and so it was not the reason of the omental
      flap necrosis. Devascularisation of the great gastric curvature until to the root
      of the left gastroepiploic artery, administration of the prophylactic doses of
      the Heparin and to put gently pressure on the omental flap do not contribute to
      the appearance of the omental flap necrosis. Based on our experiences and on
      results of this research we conclude that this way of forming the omental graft
      can be used for the other omentopexies.

PMID- 10951797
TI  - Cystadenomas of the pancreas.
AB  - Cystadenomas of the pancreas are rare tumors. They represent about 10% of the
      pancreatic cystic masses. Several hundred cases seem to have been reported so
      far. These tumors appear as serous and mucinous. Over 13 years period (1983-1996)
      we treated 22 patients for cystadenoma of the pancreas. All patients were women.
      There were 6 serous and 16 mucinous cystadenomas. The average age in the serous
      group was 31 years (ranging from 23 to 42 years) and 43 years (ranging 17-64) in
      mucinous group. Two patients had tumor in the head, 20 others in the tail and
      body of the pancreas. The diameter of these tumors varied from 3.5 to 17.0 cm
      (average 9.6 cm). The leading symptoms were epigastric or left subcostal pain in
      19 patients, palpable mass in 10, weight loss in 5, vomiting in 5, and melena in
      one patient. Tumor was accidentally found in a women undergoing abdominal
      operation for enteric fistula after hysterectomy. Serum amylase was moderately
      elevated in two patients. Diagnosis of pancreatic cystadenoma was proposed
      preoperatively in 16 patients (72.7%). In other cases, diagnoses of pancreatic
      cysts in 5 patients or hydatid cyst in 1 patient were made. An ideal operative
      removal (excision) was done in 7 patients, both excision of the tumor and
      splenectomy in 2, while distal pancreatectomy and splenectomy were carried out in
      13 others. There was no mortality. One female patient developed left subphrenic
      abscess and left pleural effusion which were successfully treated by drainage and
      thoracocenthesis. One patient developed transient pancreatic fistula. All
      patients have been under close follow-up from 6 months to 13 years and all stayed
      symptom free so far.

PMID- 10951798
TI  - Role of autologous fibrin tissue adhesive in abdominal surgery.
AB  - Fibrin tissue adhesive (FTA) is an agent developed for achieving better
      hemostasis and adhesion of living tissue. FTA appears to have no tissue toxicity,
      promotes a firm seal in seconds to minutes, is reabsorbed in days to weeks
      following application, and appears to promote local tissue growth and repair. It
      can be used in various surgical procedures. It has been used preoperatively,
      perioperatively and postoperatively in abdominal surgical procedures. There were
      no side effects. Improvement of surgical hemostasis was obvious in all patients.
      Anastomotic leakages were closed in a shorter time without surgical intervention.
      Sero-lymphatic drainage after surgical procedures that include extensive lymph
      node dissections was less. Use of FTA in treatment of fistula in ano was
      successful. The data would indicate that use of FTA may be a good alternative in
      solving various conditions in every day clinical practice, although a bigger
      randomized series, and longer follow up is needed.

PMID- 10951800
TI  - [The presence and significance of Helicobacter pylori in patients with
      enterogastric reflux].
AB  - The aim of the study is assessment of the relationship between enterogastric
      reflux and the presence of Helicobacter pylori infection as a factors that cause
      gastritis, peptic ulcer and adenocarcinoma ventriculi. The study was performed in
      52 patients with different digestive disorders, using gamma camera, during 90
      minutes (1 frame/min) after intravenous injection of 185 MBq 99mTc-dietil IDA in
      cubital vein. According to time activity curves from the region of hepatobiliary
      system and gaster, index of enterogastric reflux was assessed (EGR). There is no
      correlation between the presence of Helicobacter pylori and EGR (r = 0.181, DF =
      52, P < 0.05). However, Helicobacter is present more frequently in the patients
      with positive EGR (p 0.01). However, there is no significant difference (p <
      0.05) in reflux value in patients with both positive and negative finding of
      Helicobacter.

PMID- 10951799
TI  - [Epidural analgesia in total gastrectomy--combination of bupivacaine with
      ketamine or fentanyl].
AB  - The effects of intraoperative epidural administration of ketamine added to
      bupivacaine were compared with fentanyl added to bupivacaine in patients
      undergoing total gastrectomy. Prospective, randomized, double blind study was
      designed to compare: group F: 20 patients (pts) receiving 20 ml of 0.125%
      bupivacaine and 50 ug of fentanyl and group K: 20 pts in whom 20 ml of 0.125%
      bupivacaine was combined with 50 mg of ketamine. Pts received an epidural
      injection through peridural catheter introduced through either T7-8 or T8-9
      interspinous space. Non invasive arterial blood pressure, heart rate and ECG were
      recorded every 5 mins. We measured supplementary fentanyl requirement, ephedrine
      consumption, first postoperative complain on pain, tracheal extubation time. The
      groups were comparable with regard to patients characteristics, operation and
      anaesthesia related factors. There were no difference between groups in mean
      intraoperative fentanyl requirements (F vs. K = 118.5 (122.5) ug vs.
      122.5(122.5)ug) (p n > 0.05), in the duration of epidural pain relief (F vs. K =
      393.72 (98.75)min vs.403.63 (111.41)min, in the tracheal extubation time (F vs.K
      = 52.31 (50.4) vs.46.75 (48.35) min), postoperative sedation score (F vs.K = 1.26
      (0.73) vs.1.11 (0.32)) (p > 0.05). Significantly higher systolic blood pressure
      was measured in group K comparing with group F in 20, 75, 105, 120, 150 min (p >
      0.05). Statistically significant more ephedrine was applied in F group (F vs.K =
      0.88(1.76)ml vs.0.05(0.23)ml) (p > 0.05). There were no statistically significant
      differences between groups in heart rate during the operation. None of the pts
      complained of bad dreams or awakeness during operation. Both fentanyl and
      ketamine added to bupivacaine and given as a bolus provided good intraoperative
      analgesia in combination with general anaesthesia, minimal sensorimotor
      disturbance and early tracheal extubation. In our study fentanyl added to
      bupivacaine caused higher incidence of hypotension than ketamine added to
      bupivacaine.

PMID- 10951801
TI  - [Pharyngo-esophageal reconstruction].

PMID- 10951802
TI  - [Respiratory insufficiency and lipomatosis of the neck (Madelung's neck)].
AB  - A case of Madelungs neck is reported. After two operations in three years the
      patient developed respiratory insufficiency and transferred to our hospital in
      state of severe suffocation for tracheotomy. The factors leading to suffocation,
      such as inspiratory dyspnea, factors influencing the patient to undergo an
      operation and therapy, and difficulties encountered by an ENT surgeon in managing
      a respiratory crisis by tracheotomy are highlighted. The reported case
      illustrates an emergency tracheotomy in a very advanced stage of the disease.

PMID- 10951803
TI  - [Surgical management of a ruptured aneurysm of the common carotid artery--case
      report].
AB  - A case report on 80-year patient ruptured aneurysm of the common carotid artery
      (CCA), immediately below its branching which leading to pulsatile mass on the
      neck. Fifteen days later skin perforation and external hemorrhage ensued. The
      diagnosis was established by clinical examinations, ECHO duplex scan US,
      arteriography of carotid arteries and CT of the neck (cervical CT). The patient
      underwent emergency surgical procedure in general endotracheal anesthesia. The
      approach to the rupture site was hindered by the massive hematoma and thus CCA,
      ICA and ECA were trapped. Arteriotomy of ICA and CCA was performed and
      intraluminal shunt placed (inserted). Perforation site was managed using
      endoluminal Dacron patch fixating by continuous Prolen suture. Narrow Dacron
      patch was used for closing arteriotomy. The complete surgical procedure lasted 45
      minutes. Immediate and 6-th and 12 month follow up examination were conducted
      (Duplex scan, carotid artery DSA) evidencing no neurological deficits or any
      other complications. Preoperative condition, intraoperative findings and
      postoperative course were clearly and thoroughly documented. The author found
      endoluminal patch plasty at the site of the rupture-induced defect to be simple
      and safe method.

PMID- 10951804
TI  - [Hernia of the foramen Morgagni].
AB  - Left-side Morgagni's hernia described in this paper is a quite rare in surgery.
      Its usually asymptomatic and its almost always discovered accidentally, as a
      secondary medical findings. That was a case with our patient too. Diagnosis is
      usually confirmed by chest and abdominal X-rays or barium radiography. To prevent
      possible complications, surgical treatment is advised in all cases. We used
      transabdominal approach which was recommended in the literature. Surgical
      treatment was easy to perform and gave favourable results. There were no
      postoperative complications and in two years term there were no relapse.

PMID- 10951805
TI  - [Reconstruction of the long bones and mandible with vascularized fibular grafts].
AB  - In two prospective studies at the Clinic for Plastic Surgery and Burns and Clinic
      for Maxillofacial Surgery of the Military Medical Academy in the period from 1991
      to 1996 we performed 47 transplantations of the vascularized fibular graft in
      order to compensate bone defects of the long bones and mandibular inflicted by
      war wounding. The importance of the length of the vascular pedicle preparation
      for the total success was pointed out as well as the immobilization of the elbow
      region for the compensation of the defects of the upper arm and forearm and total
      healing of the mandibular for the later functional rehabilitation. The realized
      primary efficiency of 70.2% and total successfulness of 93.6% indicated that at
      the compensation on of bone defects the etiology of war wound could be compared
      to the etiology of malignant tumors resection and trauma.

PMID- 10951806
TI  - [Arterial arcades of the head and neck of the pancreas].
AB  - The arterial vascularization of the right half of pancreas is structured as
      arcades: anterior, intermediate and posterior pancreatico-duodenal, and
      prepancreatic arcade. These blood vessels present as a complex of anastomoses
      between the large viceral arteries: the coeliac trunk and the superior mesenteric
      artery. The paper describes variations of origin, course and branching of the
      arcades' constituents, relevant for the contemporary surgery of pancreas and
      adjacent organs. A particular attention was drawn to the two anatomical entities:
      retropancreatic fibrous band and arterial vascularization of the major duodenal
      papilla.

PMID- 10951807
TI  - General principles of chemotherapy.
AB  - Chemotherapy relatively recently became an available tool for treating cancer. It
      is now used at some time during the course of the disease of most patients either
      for cures for palliative reasons. Approximately two-thirds of cancer patients
      will develop recurrent of disseminated neoplastic disease and become candidates
      for systemic treatment.

PMID- 10951808
TI  - [Laparoscopy in gynecologic oncology].
AB  - Using technological progress, laparoscopic lymphadenectomy is becoming a standard
      for staging of pelvic cancer. In the same way more extensive procedures such as
      para-aortic lymph nodes dissection and radical hysterectomy have been
      demonstrated to be feasible by laparoscopy. In the future, because of its well
      known advantages, laparoscopic surgery may appear as a way to decrease the
      consequences of oncologic treatments in patients with low risk tumors and to
      propose more aggressive treatments of patients with bad prognosis tumors.

PMID- 10951810
TI  - [Diagnosis and therapy of adult respiratory distress syndrome in acute
      pancreatitis].
AB  - Acute pancreatitis has high morbidity and mortality. The treatment of these
      patients includes careful respiratory monitoring. Adult Respiratory Distress
      Syndrome could be find in 50% of patients, while 40% of these needs intensive
      care.

PMID- 10951809
TI  - [Mechanisms in onset of postoperative immunodepression and its importance in the
      surgical treatment of cancer patients].
AB  - Postoperative immunodepression is inevitable transient path of operative trauma.
      Changes in the immunologic status are related to the duration of the anesthesia
      and surgery procedure. Mortality and morbidity and recurrence rate may be related
      with immunodepression.

PMID- 10951811
TI  - [Evaluation of enterogastric reflux using a modified scintigraphy method].
AB  - The aim of the study is evaluation of the clinical validity of the chosen and
      modified own model of the nuclear medicine method for the detection and
      quantification of enterogastric reflux (EGR), as well as evaluation of its
      clinical validity. The study was performed in 172 patients: with gastric and
      duodenal ulcer, after Billroth I and Billroth II gastrectomy, with
      gastroesophageal reflux, after cholecystectomy, with chronic cholecystitis and
      chronic duodenal disease. Acquisition was performed with gamma camera, during 90
      minutes after intravenous application of 185 MBq 99m-Tc-Dietil IDA. Test meal was
      given in 30th minute, while gastric region was marked at the end of the study. On
      the basis of the radioactivity changes in the regions of the stomach and
      hepatobiliary system, presence of enterogastric reflux is determined and its
      index calculated. In all the groups of patients, values are significantly
      different from physiological. The most frequent occurrence and the largest
      quantity of reflux is present in patients after Billroth II gastrectomy with
      significantly different values from other groups of patients. The obtained
      results approve clinical value of the chosen and modified scintigraphy of EGR as
      a non-invasive and physiological method, which provides data about its presence
      and quantity.

PMID- 10951812
TI  - [Splenectomy in the treatment of hematologic diseases].
AB  - After first splenectomy performed 1888 for spherocytosis until now, a number of
      hematological indications for therapeutical splenectomy were described, with
      established preoperative treatment and more favorable postoperative results in
      recent studies. In the period between 1985 and 1997, 130 splenectomies for
      hematological disorders were performed on Department of surgical
      gastroenterology, 1st Surgical Clinic. The indications were as follows: 72
      patients with autoimmune hematological diseases (55.38%), 28 patients with
      lymphoproliferative diseases (21.54%), Hodgkin-s disease in 11 patients (8.46%),
      myeloproliferative diseases in 6 (4.62%), splenectomy as a part of staging
      laparotomy in patients (7.69%), and for other hematological disorders in 3
      patients (2.31%). Most of the removed spleens (95) weighted from 500 to 1500 g
      (73.08%). In 19 patients spleens weighted less then 500 g (14.62%), and in 16
      patients more then 1500 g (12.31%). There was no significant correlation between
      the weight of the removed spleen and the incidence of postoperative
      complications. In 8 patients with preoperative thrombocytopenia (6.16%),
      intraoperative infusions of fresh thrombocytes were used. In 12 patients (9.23%)
      postoperative complications occurred, mainly in the patients who received
      immunosuppressive therapy preoperatively in excessive amounts, and were disease
      dependent. Overall mortality was 4 (3.12%), and in 2 patients there was "exitus
      in tabular". Delayed results depended of basic hematological disorder and
      supportive treatment. The surgical particularities of the operative procedure are
      discussed, as well as the perioperative treatment and certain aspects of teamwork
      of hematologist and surgeon.

PMID- 10951813
TI  - [Histopathologic changes in the skin of transplanted microvascular flaps].
AB  - During the microvascular transfer, the free flaps tissue is exposed to series of
      pathophysiological changes (tissue anoxia, tissue acidosis, anaerobic metabolism,
      wound healing and cicatrisation, degeneration of nerves fibers in the free flaps
      tissue, etc.) In 1993-1998 period, at the Clinic for Plastic Surgery and Burns at
      the Military Medical Academy, we analyzed histopathologic changes in the skin
      taken from the transferred flaps and from the recipient region surroundings of 31
      patients with microvascular tissue transfer. The bioptic materials were taken
      between 6 and 36 months following the free tissue transfer--average 23.6 months.
      By light microscopy we analyzed histopathologic changes of the epidermis,
      collagen's fibers, skin adnexa, blood vessels and nerve fibers. The data obtained
      showed considerable difference in the histopathology test results of the
      epidermis, collagen's fibers, the skin adnex and the nerve fibers in the
      transferred free flaps compared to the results obtained from testing recipient
      region surroundings. The histopathologic tests of the blood vessels did not show
      considerable comparative difference.

PMID- 10951814
TI  - [Advantages of laparoscopically-assisted vaginal hysterectomy in comparison with
      the traditional approach].
AB  - The authors are discussing the advantages of the laparoscopically assisted
      vaginal hysterectomy over the traditional vaginal method, comparing two groups of
      patients operated in both techniques. In 30 patients from the first group the
      traditional vaginal hysterectomy have been performed as part of the operation
      needed in order to change their sex. 20 patients from the second group have been
      operated, due to different indications, by laparoscopically assisted vaginal
      hysterectomy. Comparing the indications, the operation itself and the results in
      postoperative treatment the authors concluded that, for the laparoscopically
      assisted vaginal hysterectomy the indications are more numerous, practically
      there are no contraindications, the operation itself is easier, because all
      abdominal organs are visible on the screen. As for the results after the
      operation, they are almost identical in both groups. The only advantage of the
      traditional method is that, sometimes, the operation itself does not last long.
      The greatest benefit of laparoscopic assisted vaginal hysterectomy is the
      potential to convert what would have been an abdominal hysterectomy into a
      vaginal hysterectomy. The authors unanimously concluded that only experienced
      surgeons can perform both operations.

PMID- 10951815
TI  - [The popliteal artery entrapment syndrome].
AB  - The authors are presenting 8 patients with 9 cases of popliteal artery entrapment
      syndrome. There were one female, and 7 male patients with average age of 36.4 (25
      54) years. Six cases were manifested with acute, 2 with chronic foot ischemia,
      while one case was asymptomatic. For diagnosis a combination of Doppler
      sonography and transfemoral angiography, was used. Eight cases were operated
      using posterior, while in one medial approach to the popliteal artery. The types
      I and IV of the popliteal artery entrapment syndrome were found in one case, type
      II in two cases, type III in 4 cases, while in one case a type of syndrome had
      not to be identified. During the operation the resection of the anomalous muscle
      and reconstruction of the popliteal artery, were done in 8 cases. In one case
      muscle resection or arterial reconstruction, were not necessary. The early
      potency rate and limb salvage, were 100%, while long term potency rate after mean
      follow up period of 6.3 years was 83.5%. The acute or chronic foot ischemia in
      health, young persons without typical atherosclerotical risk factors, suggests on
      popliteal artery entrapment syndrome.

PMID- 10951816
TI  - [Endoscopy of the esophagus, stomach and duodenum at Victoria Hospital-
      Seychelles].
AB  - From 1992-1995 in Victoria Hospital Republic of Seychelles 1037 patients
      undergone esophago-gastro-duodenoscopic examination. Ulcer was find in 26%
      patients, gastritis in 23.5%, gastroesophageal reflux in 15.9%, upper gastro
      intestinal bleeding in 13.5%., carcinoma of the esophagus in 6%, gastric ulcer in
      2.8%, hiatus hernia in 3%, esophageal varices in 2.1%, gastric carcinoma in 2.1%
      and 0.3% with polyps.

PMID- 10951817
TI  - The value of ultrasound in staging the severity of acute pancreatitis.
AB  - The authors asses the accuracy and role of early ultrasound examination in
      staging the severity of acute pancreatitis. A total of 110 consecutive patients
      with acute pancreatitis were included into the study. The ultrasound findings
      were categorized into six categories and compared with a modification of multiple
      prognostic criteria, computerized tomography, operative findings (when available)
      and clinical outcome. The probability of a positive ultrasound finding in a
      patient with clinically severe acute pancreatitis was 89.6% (sensitivity). In
      comparison to computerized tomography the sensitivity of ultrasound in
      discovering CT diagnosed moderate and severe forms of acute pancreatitis was
      86.6%. The sensitivity of ultrasound in discovering moderate and severe forms of
      acute pancreatitis as defined at laparotomy was 77.8%. The specificity of
      ultrasound was low (44.0%) in comparison with modified prognostic criteria, but
      high in comparison with computerized tomography (87.5%) and staging at laparotomy
      (85.7%). There was a good correlation between US defined moderate and severe
      forms of acute pancreatitis and clinical outcome (average number of hospital days
      and case fatality). The authors conclude that early ultrasound examination in
      acute pancreatitis is indicated and can help stage the severity of the disease
      and affect decision making.

PMID- 10951818
TI  - [Spontaneous massive retroperitoneal hemorrhage from an adrenal gland cyst].
AB  - Adrenal cyst are rare disease. Bleeding, particularly massive, from these cysts
      is even rarer. The cyst causing spontaneous massive retroperitoneal bleeding in a
      17 year old girl is presented. Adrenalectomy was successfully carried out. The
      patient stayed symptom free so far.

PMID- 10951820
TI  - [Transduodenal sphincteroplasty].

PMID- 10951821
TI  - [Surgical treatment of superficial femoral vein thrombosis--a new technique].
AB  - In 4 patients who suffered from superficial vein thrombosis new technique was
      applied. The main issue of this technique are: ligation of superficial vein in
      the point inferior to vein profunda femoris and sapheno-popliteal vein
      anastomoses. In two patients sapheno-popliteal anastomoses was competent after
      30,18 months. In one patient sapheno-poplietal anastomoses was incompetence after
      3 months. And one patient was lost for follow-up.

PMID- 10951819
TI  - [Anatomic and surgical aspects of intrahepatic segmentation].
AB  - This article presents anatomical and surgical patterns of hepatovenous and portal
      segmentation in the human liver. Special attention was drawn to the significance
      of portal fissures, their projections and surgical approach to large blood
      vessels. The anatomical variations of hepatic veins and the constituents of the
      portal triad (with particular surgical importance) were also included. Finally,
      the study gives a brief description of the perivascular fibrous capsule
      morphology and its relations to the portal bifurcation.

PMID- 10951822
TI  - Risk factors for atherosclerosis in an elderly outpatient population in the city
      of Sao Paulo.
AB  - OBJECTIVE: To analyze in out clinic elderly patients of both sexes for the
      prevalence of risk factors for atherosclerosis and study their association with
      the complications of atherosclerosis. METHODS: Five hundred and sixteen
      outpatients, 152 men and 364 women, 60 years or older, were studied. The
      prevalences of hypertension, dyslipidemia, diabetes mellitus, cigarette smoking
      and obesity were determined in both sexes and compared using the chi-square test.
      The association between these factors and the presence of atherosclerotic
      complications was analyzed by logistic regression. RESULTS: The comparative
      analysis of the factors in both sexes showed that hypertension, total cholesterol
      > or = 240 mg/dL, LDL-cholesterol > or = 160 mg/dL, and body mass index > 27.5
      were more frequent among women, but HDL-cholesterol < 35 mg/dL and cigarette
      smoking were more frequent among men, and no difference occurred between sexes in
      relation to the frequency of triglycerides > or = 250 mg/dL and diabetes
      mellitus. After adjustment of the variables in the regression model, we observed
      that in the total of elderly patients, risk factors for complications of
      atherosclerosis were: triglycerides > or = 250 mg/dL, hypertension, and male sex.
      Among men, the risk factors were: LDL-cholesterol > or = 160 mg/dL, diabetes
      mellitus, HDL-cholesterol < 35 mg/dL and hypertension. Among women, the risk
      factors were: triglycerides > or = 250 mg/dL and hypertension. CONCLUSION: The
      results showed that, in the elderly, the risk factors for atherosclerosis
      persist, but with different behaviors between men and women. The study suggests
      that the relative importance of the risk factors can change with the aging
      process.

PMID- 10951823
TI  - Heart transplantation in neonates and children. Intermediate-term results.
AB  - OBJECTIVE: To assess intermediate-term outcome in children who have undergone
      orthotopic heart transplantation. METHODS: We carried out a longitudinal and
      prospective study between October '92 and June '99 comprising 20 patients with
      ages ranging from 12 days to 7 years (mean of 2.8 years). We employed a double
      immunosuppression protocol with cyclosporine and azathioprine and induction
      therapy with polyclonal antithymocyte serum. Survival and complications resulting
      from the immunosuppression protocol were analyzed. RESULTS: The double
      immunosuppression protocol and the induction therapy with polyclonal
      antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1
      and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient
      died due to acute rejection 40 days after transplantation; another patient died 2
      years after transplantation due to lymphoproliferative disorder; a third patient
      died because of primary failure of the graft; and a fourth patient died due to
      bronchopneumonia. The major complications were as follows: acute rejection,
      infection, nephrotoxicity, and systemic hypertension. The means of rejection and
      infection episodes per patient were 2.9 and 3.4, respectively. After one year of
      transplantation, a slight reduction in the creatinine clearance and systemic
      hypertension were observed in 7 (38.9%) patients. CONCLUSION: Heart
      transplantation made life possible for those patients with complex congenital
      heart diseases and cardiomyopathies in refractory congestive heart failure
      constituting a therapeutical option for this group of patients in the terminal
      phase.

PMID- 10951824
TI  - Effects of a novel fermented soy product on the serum lipids of
      hypercholesterolemic rabbits.
AB  - OBJECTIVE: To assess the effect of a new feed soy product fermented by
      Enterococcus faecium and Lactobacillus jugurti on the serum lipid levels of
      rabbits with induced hypercholesterolemia. METHODS: Thirty-two rabbits were
      divided into 4 groups as follows: 1) control (C); 2) hypercholesterolemic (H); 3)
      hypercholesterolemic + fermented product (HPF); and 4) control + fermented
      product (CPF). The H and HPF groups were fed with a diet with 0.15% (p/p)
      cholesterol in the first 15 days. C and CPF groups received regular food
      preparation. The HPF and CPF groups received 10 mL daily of the fermented 30
      days. Blood samples were drawn at the beginning of the study and at the 15th and
      30th days. Concentrations of total cholesterol, HDL-cholesterol, and
      triglycerides were analyzed. RESULTS: After 15 days, the HPF group showed a total
      cholesterol concentration lower (18.4%) than that of the H group (p = 0.05), but
      this difference disappeared after 30 days. No change was observed in total
      cholesterol levels of C and CPF groups. After 15 days, the HDL-cholesterol was
      higher (17.8%) in the HPF group, but the triglyceride levels remained unchanged
      in all groups during the same period of time. CONCLUSION: The soy fermented
      product caused an 18.4% reduction in total cholesterol and a 17.8% increase in
      the HDL-fraction. It may, therefore, be a possible coadjutor in the treatment of
      hypercholesterolemia.

PMID- 10951825
TI  - A study of infectious endocarditis in Ribeirao Preto, SP-Brazil. Analysis of
      cases occurring between 1992 and 1997.
AB  - OBJECTIVE: To analyze the epidemiology, diagnosis, clinical aspects causes and
      evolution of infectious endocarditis. METHODS: The patients analyzed were treated
      at the University Hospital of the Faculdade de Medicina of Ribeirao Preto-USP and
      had a diagnosis of infectious endocarditis defined by Duke's criteria, which
      classifies infectious endocarditis as native, prosthetic valve or that occurring
      in intravenous drug users. RESULTS: One hundred and eighty episodes of infectious
      endocarditis in 168 patients were observed. Echocardiograms in 132 (73.3%)
      provided a diagnosis of infectious endocarditis in 111 (84%) patients; mitral
      valves were affected in 55 (30.5%), tricuspid valves in 30 (16.6%) and the aortic
      valve in 28 (15.5%) patients. Hemocultures were performed in 148 (93.8%) episodes
      of IE. The most commonly isolated infectious organisms were Staphylococcus aureus
      in 46 (27.2%) patients and Streptococcus viridans in 27 (15.9%). Complications
      occurred in 116 (64.4%) patients and 73 (40.5%) of the patients died. CONCLUSION:
      The general profile of the observed infectious endocarditis was similar to that
      reported in studies performed in other countries and included users of
      intravenous drugs. The high degree of mortality observed is not compatible with
      progress in diagnosis and treatment of infectious endocarditis and is probably
      due to the absence of diagnostic suspicion. The high frequency of fatal cases of
      septicemia (45.1% of deaths) in the patients studied indicates that unnoticed
      cases of infectious endocarditis had only been diagnosed at necropsy.

PMID- 10951826
TI  - Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of
      a double-blind randomized placebo-controlled study (CARIBE study).
AB  - OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic
      dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled
      study, 30 patients (7 women) with functional class II and III heart failure were
      assessed. Their ages ranged from 28 to 66 years (mean of 43 +/- 9 years), and
      their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was
      added to the usual therapy of 20 patients; placebo was added to the usual therapy
      of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased
      weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical
      assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography
      were performed in the pretreatment phase, being repeated after 2 and 6 months of
      medication use. RESULTS: A reduction in heart rate (p = 0.016) as well as an
      increase in left ventricular shortening fraction (p = 0.02) and in left
      ventricular ejection fraction (p = 0.017) occurred in the group using carvedilol
      as compared with that using placebo. CONCLUSION: Carvedilol added to the usual
      therapy for heart failure resulted in better heart function.

PMID- 10951828
TI  - Isolated noncompaction of the myocardium.
AB  - We report the case of a 42-year-old female with fatigue on exertion and
      palpitation consequent to the existence of isolated noncompaction of the
      myocardium. We discuss clinical and familial findings, diagnostic possibilities,
      and prognostic and therapeutical implications of this rare disorder of
      endomyocardial morphogenesis.

PMID- 10951827
TI  - Right coronary artery fistula with congestive heart failure in the neonate.
      Doppler echocardiographic diagnosis and closure with detachable balloon.
AB  - We report here a case of coronary artery fistula in a neonate with clinical signs
      of heart failure. The electrocardiogram showed signs of left ventricular
      hypertrophy and diffuse alterations in ventricular repolarization. Chest X-ray
      showed an enlargement of the cardiac silhouette with an increase in pulmonary
      flow. After echocardiographic diagnosis and angiographic confirmation, closure of
      the fistulous trajectory was performed with a detachable balloon with an early
      and late successful outcome.

PMID- 10951829
TI  - Valvular regurgitation by color Doppler echocardiography.

PMID- 10951830
TI  - [Single daily dose of verapamil (COER-24 180/24 mg) in mild and moderate
      hypertension evaluated by ambulatory blood pressure monitoring].
AB  - OBJECTIVE: To evaluate the anti-hypertensive effect of verapamil COER-24 180/240
      mg in a single dose at bedtime as single therapy in mild to moderate
      hypertensives. METHODS: A multicentric, open, placebo controlled study of 81
      hypertensive patients older than 20 years-old followed to 8 weeks. Blood pressure
      was measured in doctor's office and by 24 h ambulatory monitoring (ABPM).
      RESULTS: We observed a decreased in systolic and diastolic blood pressure in
      doctor's office at 4th and 8th weeks. ABPM showed that both systolic, diastolic
      and mean blood pressure, heart rate and the mean 24-hour blood pressure load
      decreased after the 8-week treatment. In addition, there was a reduction of the
      double-product, especially in the morning and 68% of the patients didn't have any
      adverse events. CONCLUSION: The therapy verapamil COER-24 180/240 mg in a single
      dose is useful for mild and moderate hypertensive patients, with significant
      pressure decrease in both office blood pressure measurements and in the ABPM/24
      hours, as well as showing good tolerability.

PMID- 10951831
TI  - Epidemiological characteristics of congenital heart diseases in Londrina, Parana
      south Brazil.
AB  - OBJECTIVE: To determine the prevalence and other epidemiological characteristics
      of congenital heart diseases. METHODS: A retrospective population based study of
      children who were born in Londrina, from January '89 to December '98 (80,262 live
      births). Diagnoses were confirmed through autopsy, surgery, catheterization, or
      echocardiography. RESULTS: A total of 441 patients was as certain what
      corresponds to a prevalence of 5.494:1,000 live births. Ventricular septal defect
      was the commonest lesion. A small number of transpositions of the great vessels
      and of left ventricular hypoplasia was observed. A high propation of ventricular
      septal defect (28.3%) and atrioventricular septal defects (8.1%) occurred. Fifty
      one (11.35%) affected children had syndromic diseases and 52 (12.01%) children
      had nonsyndromic anomalies. CONCLUSION: The prevalence of congenital heart
      diseases in Londrina is in accordance with that of other regions of the globe.
      This prevalence also may reflect the reality in the southern region of Brazil,
      because population characteristics are very similar in the 3 southernmost
      Brazilian states.

PMID- 10951832
TI  - Efficacy of a diagnostic strategy for patients with chest pain and no ST-segment
      elevation in the emergency room.
AB  - PURPOSE: To evaluate the efficacy of a systematic model of care for patients with
      chest pain and no ST segment elevation in the emergency room. METHODS: From 1003
      patients submitted to an algorithm diagnostic investigation by probability of
      acute ischemic syndrome. We analyzed 600 ones with no elevation of ST segment,
      then enrolled to diagnostic routes of median (route 2) and low probability (route
      3) to ischemic syndrome. RESULTS: In route 2 we found 17% acute myocardial
      infarction and 43% unstable angina, whereas in route 3 the rates were 2% and 7%,
      respectively. Patients with normal/non-specific ECG had 6% probability of AMI
      whereas in those with negative first CKMB it was 7%; the association of the 2
      data only reduced it to 4%. In patients in route 2 the diagnosis of AMI could
      only be ruled out with serial CKMB measurement up to 9 hours, while in route 3 it
      could be done in up to 3 hours. Thus, sensitivity and negative predictive value
      of admission CKMB for AMI were 52% and 93%, respectively. About one-half of
      patients with unstable angina did not disclose objective ischemic changes on
      admission. CONCLUSION: The use of a systematic model of care in patients with
      chest pain offers the opportunity of hindering inappropriate release of patients
      with ACI and reduces unnecessary admissions. However some patients even with
      normal ECG should not be released based on a negative first CKMB. Serial
      measurement of CKMB up to 9 hours is necessary in patients with medium
      probability of AMI.

PMID- 10951833
TI  - Mediastinitis after cardiac transplantation.
AB  - OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac
      transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were
      performed, 12 (5.6%) of the transplanted patients developed confirmed
      mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3 +/- 10.0
      years) and 10 (83.3%) patients were males. Seven (58.3%) patients showed sternal
      stability on palpation, 4 (33.3%) patients had pleural empyema, and 2 (16.7%)
      patients did not show purulent secretion draining through the wound. RESULTS:
      Staphylococcus aureus was the infectious agent identified in the wound secretion
      or in the mediastinum, or both, in 8 (66.7%) patients. Staphylococcus epidermidis
      was identified in 2 (16.7%) patients, Enterococcus faecalis in 1 (8.3%) patient,
      and the cause of mediastinitis could not be determined in 1 (8.3%) patient.
      Surgical treatment was performed on an emergency basis, and the extension of the
      debridement varied with local conditions. In 2 (16.7%) patients, we chose to
      leave the surgical wound open and performed daily dressings with granulated
      sugar. Total sternal resection was performed in only 1 (8.3%) patient. Out of
      this series, 5 (41.7%) patients died, and the causes of death were related to the
      infection. Autopsy revealed persistence of mediastinitis in 1 (8.3%) patient.
      CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical
      drainage have changed the natural evolution of this disease. Nevertheless,
      observance of the basic precepts of prophylaxis of infection is still the best
      way to treat mediastinitis.

PMID- 10951834
TI  - Absence of the aortic valve associated with hypoplastic left-sided heart
      syndrome.
AB  - In this report we describe the twelfth case in the literature of absence of the
      aortic valve cusps, associated with hypoplastic left-sided heart syndrome in a
      neonate. Clinical and hemodynamic conditions in our patient resemble the
      classical features of this syndrome except for a greater development of the
      ascending aorta and the left ventricular cavity, due to aortic insufficiency. A
      patch was unsuccessfully inserted at the aortic annulus to exclude the left
      ventricle from the circulation. In addition the Norwood operation was performed.

PMID- 10951835
TI  - The Brugada syndrome. Outcome of one case.
AB  - The Brugada syndrome is a rare condition, and due to its mutating manner of
      presentation it may be difficult to diagnose. We report one case and discuss the
      diagnostic aspects and the clinical outcome of one patient with characteristic
      findings of this syndrome. These findings are especially defined by J-ST
      elevation in the right leads of serial electrocardiographic records, wide
      oscillations of J points and ST segments during 24-hour Holter monitoring, and
      nocturnal sudden death. We stress the importance of the Holter monitor findings
      for diagnostic complementation. Through this method it is possible to establish a
      correlation between vigil activities and sleep and the variability of the degree
      of impairment in ventricular repolarization.

PMID- 10951836
TI  - Association of pulmonary atresia with intact ventricular septum and aortic valve
      stenosis. Prenatal diagnosis.
AB  - A rare association of pulmonary atresia with an intact septum was diagnosed
      through echocardiography in a fetus 32 weeks of gestational age. The diagnosis
      was later confirmed by echocardiography of the newborn infant and further on
      autopsy. The aortic valve was bicuspid with a pressure gradient of 81 mmHg, and
      the right ventricle was hypoplastic, as were the pulmonary trunk and arteries,
      and the blood flow was totally dependent on the ductus arteriosus.

PMID- 10951837
TI  - An interpretation--mitral valve prolapse syndrome.

PMID- 10951838
TI  - Reconstructive surgery for aortic valve disease.

PMID- 10951839
TI  - [Guidelines for permanent cardiac pacemaker implantation].

PMID- 10951840
TI  - [Guidelines for cardioverter defibrillator implantation].

PMID- 10951841
TI  - [Hypokalemia of renal origin].

PMID- 10951842
TI  - [Evaluation of the results of percutaneous transluminal angioplasty of arterial
      stenosis in the transplanted kidney using area under time curves of the
      glomerular filtration rate and blood pressure].
AB  - The benefit of percutaneous transluminal angioplasty (PTA) of renal transplant
      artery stenosis for renal hemodynamics is frequently adversely affected by
      rejection or another complication. As a result, evaluation of the effect of PTA
      is often difficult. Our study was designed to assess the effect of PTA using a
      method of integrated value of the glomerular filtration rate (GFR) calculated on
      the basis of the area under the curve over the follow-up period (AUC0-t). A
      similar procedure was employed to evaluate mean arterial pressure (MAP). The
      method was used to assess the outcome in 20 individuals before to PTA, and at 1,
      3, 6, 9 and 12 months after angioplasty. A rejection episode was diagnosed in
      eight cases and glomerulonephritis of the graft in one. Using the evaluation of
      (AUCCcr)0-12 in relation to the integrated value before PTA (Ccr) x 12, a rise in
      GFR > 20% was found in 65% of cases. PTA failure was observed in seven
      individuals developing post-PTA complications. When assessing the integrated
      value of MAP, PTA was found to be successful (a reduction by at least 10%) in 85%
      of cases. No significant correlation was demonstrated between the integrated
      values of GFR and MAP. The results support the assumption that the evaluation of
      the integrated values of GFR or MAP using AUC0-t allows to characterize, in a
      simple manner, the degree of renal transplant function or MAP throughout the
      follow-up period, and to furnish additional information to the values obtained at
      individual time intervals after the therapeutic procedure.

PMID- 10951843
TI  - [Pharmacotherapy in patients with ischemic heart disease and diabetes mellitus in
      1998 in the Czech Republic].
AB  - The state of pharmacotherapy in the Czech Republic in 1998 was analysed in a
      group of 548 patients with coronary heart disease and diabetes mellitus. 83.0% of
      the group were treated by antiplatelet drugs, mostly ASA (with the most frequent
      dose being 100 mg). 7.3% of the patients were treated by anticoagulation
      treatment. Beta-blocking agents were used in 56.9% of the group (most frequently
      metoprolol and atenolol). The optimal dose of metoprolol, 100 mg b.i.d., was used
      in only 12.4% of the patients treated by metoprolol. Older patients and patients
      with left ventricular systolic dysfunction were treated significantly less
      frequently than younger patients or patients without left ventricular systolic
      dysfunction. ACE inhibitors were used in 52.2% of the patients. The optimal daily
      target dosages of captopril 100-150 mg were used in only 6% of patients treated
      by captopril. The optimal target daily dosages of enalapril were used in only
      35.1% of patients treated by enalapril. 65% of patients with left ventricular
      systolic dysfunction were treated by ACE inhibitors. Calcium-channel blockers
      were used in 24.6% of the patients. However, in 20.1% of patients treated by
      calcium-channel blockers, shortacting or inadequately retarded nifedipine was
      used. 69.8% of the patients had total cholesterol values higher than 5.2 mmol/l,
      18.1% higher than 6.2 mmol/l and 13.5% of patients had total cholesterol values
      higher than 7.0 mmol/l. 34.3% of the group were treated by hypolipidemic drugs
      (most frequently fenofibrate). Statins were used by 45.5% of patients treated by
      hypolipidemic drugs. When compared to our analysis of pharmacologic treatment in
      patients after myocardial infarction, performed in 1995, ACE inhibitors and
      hypolipidemic treatment are used more frequently. However, in spite of this
      improvement, only about 15% of patients with CHD are treated by statins.
      Furthermore, 35% of patients with left ventricular systolic dysfunction due to
      CHD are not treated by ACE inhibitors. Elderly patients with CHD and diabetes
      mellitus or patients with left ventricular systolic dysfunction due to CHD are
      less frequently treated than younger patients or those with normal left
      ventricular systolic function despite the fact that patients at highest risk
      benefit most from treatment with beta-blocking agents. Also unsatisfactory is the
      use of not retarded or inadequately retarded nifedipine although data show its
      use may increase total mortality in CHD patients. By contrast, use of
      antiplatelet therapy is satisfactory.

PMID- 10951844
TI  - [Relation of serum leptin levels and regulation of resting energy expenditure].
AB  - Leptin is a protein hormone produced by adipocytes. Its serum concentrations in
      the most of cases positively correlate with total body fat content and body mass
      index (BMI). Leptin plays a role in the food intake regulation. It also increases
      resting energy expenditure in hypoleptinaemic ob/ob mice. Its relationship to
      resting energy expenditure in human is less clear. The aim of our study was to
      follow the serum leptin levels in healthy females (n = 12) and males (n = 14) and
      their relationship to resting energy expenditure, body fat content, other
      antropometric and nutritional biochemical parameters. It was found that serum
      leptin levels were significantly higher in females comparing to males (6.8 +/- 3
      ng.ml-1 vs. 2.6 +/- 1 ng.ml-1, p < 0.05). The serum leptin levels correlated
      positively with body fat content and body mass index in both groups. In females
      the positive correlation between body weight and serum leptin levels was found.
      No statistically significant relationship between serum leptin levels and resting
      energy expenditure, serum total protein, albumin or prealbumin concentration was
      found in any of studied groups. The results of our study do not testify to direct
      relationship between serum leptin levels and resting energy expenditure in young
      healthy individuals.

PMID- 10951845
TI  - [Detection of multiple myeloma cells using multicolor immunofluorescence and flow
      cytometry].
AB  - The advent of new therapeutic approaches to multiple myeloma made necessary the
      introduction of novel methods for detection of minimal residual disease. Among
      others approaches residual disease can be detected by the immunofluorescence
      using flow cytometry. We have examined the co-expression of CD19, CD38, CD45,
      CD54, CD56, and CD138 molecules in cells of peripheral blood and bone marrow
      aspirates in patients with multiple myeloma by 3-color flow cytometry. For the
      detection and characterization of multiple myeloma cells, combinations of
      following antibodies were used: anti-CD19 FITC, anti-CD38 FITC, anti-CD38 PE,
      anti-CD54 FITC, anti-CD56 PE-Cy5, anti-CD45 PE, anti-CD45 PE-Cy5 (Immunotech) and
      anti CD138 PE (Serotec). The samples were analyzed using EPICS XL (Coulter) flow
      cytometer, and the analysis was based on at least 10,000 events. Samples from 17
      patients were analyzed. The percentage of multiple myeloma cells ranged between
      0.3% and 54.2% in bone marrow aspirates and between 0.0 and 11.8% in periferal
      blood. The expression of CD138, CD38, CD54 and CD56 molecules was found in 100%,
      100%, 85% and 68% of examined cases, respectively. In our opinion, multiple
      myeloma cells are best characterized by following combinations of antibodies:
      CD38 FITC/CD138 PE/CD45 PE-Cy5, CD54 FITC/CD138 PE/CD56 PE-Cy5 or CD54 FITC/CD38
      PE/CD 56 PE-Cy5. The identification of a malignant clone is the first and the
      most important step in the characterization of the disease, determination of its
      prognosis and the detection of residual disease after treatment. Three-color flow
      cytometry represents a method which can meet these goals.

PMID- 10951846
TI  - [Ultrasonography study of the mammary-coronary bypass].
AB  - The authors present the case of a 49-year-old female patient who was admitted
      with the diagnosis of ischaemic heart disease and the syndrome of angina pectoris
      grade IV for selective coronarography. For assessment of the affection of one
      artery, significant stenosis of the insertion of the ramus interventricularis
      anterior the authors indicated a bypass of the left mammary artery to the ramus
      interventricularis anterior. During the postoperative course the patient did not
      have any anginous symptoms or any other clinical signs suggesting ischaemia or
      necrosis of the heart muscle. During the ultrasonographic check-up examination of
      the mammarocoronary bypass the suspicion of occlusion of the graft was expressed
      and this was confirmed on angiography. An angiographically successful
      percutaneous transluminal angioplasty of occlusion of the bypass was made. During
      the subsequent ultrasonographic examination the authors suspected again graft
      occlusion and angiography confirmed a 90% stenosis. Therefore the patient was re
      operated. It appears that ultrasonographic examination of the mammacoronary
      bypass may prove useful in the diagnosis of occlusion or critical stenosis of a
      graft.

PMID- 10951847
TI  - [An attack of malignant hyperthermia caused by a combination of the effects of
      succinylcholine, increased physical exertion and alcohol abuse].
AB  - The authors submit the case-history of a 29-year-old man, followed up on account
      of liver steatosis with a toxic-nutritional etiology who developed, after
      previous increased physical exertion and alcohol abuse, fever associated with
      major muscular weakness. Gradually he developed an amental delirious state which
      was evaluated as suspect delirium tremens. Fever of 40-41 degrees C continued,
      the patient developed muscular rigidity, tremor and hypotension. After intubation
      during which succinylcholine was administered, the patient's condition
      deteriorated further with a rise of temperature and muscular rigidity. The
      patient developed acute renal failure with anuria and the necessity of repeated
      haemodialyses and severe acidosis of the mixed type on account of which he was
      intubated and switched to artificial ventilation. According to the case-history
      clinical and laboratory picture of the disease (extremely high creatine kinase
      activity, hyperkalaemia, acidosis, hepatorenal failure) malignant hyperthermia
      was suspected. After a single intravenous injection of sodium dantrolene, 2.5
      mg/kg, the temperature dropped and within 24 hours the patient was afebrile.
      Gradually the acidosis improved, the blood pressure became stabilized and
      artificial ventilation was no longer used. The patient was discharged after 34
      days in hospital in a state of cardiopulmonary compensation with mild polyuria
      but without signs of retention of nitrogenous substances with sideropenic anaemia
      and marginal creatine kinase and lactate dehydrogenase values. Within one month
      after discharge the laboratory values reached normal levels and only slight
      muscular weakness and greater fatiguability persisted.

PMID- 10951848
TI  - [Autologous stem cell transplantation in a patient with juvenile chronic
      arthritis].
AB  - In the submitted case-history the authors describe autologous haematopoietic stem
      cell transplantation (ASCT) in a patient suffering from juvenile chronic
      arthritis (JCA). ASCT was indicated by rheumatologists and haematologists for
      refractory polyarticular JCA. Mobilization with cyclophosphamide and granulocyte
      colony stimulating factor was effective in terms of CD34+ cell shift to
      peripheral blood and the good quality autograft reliably led to haematopoetic
      recovery after megachemotherapy. The peritransplant period was not complicated
      with life threatening events. Immunosuppressive effect of autotransplant has
      reduced signs of rheumatoid disease activity and enabled conventional drug dose
      reduction. Autotransplant of haematopoietic stem cells has a potential to reduce
      activity of juvenile chronic arthritis.

PMID- 10951849
TI  - [Analysis of phenotype resistance to activated protein C (APC resistance)].
AB  - The laboratory diagnosis of resistance to activated C protein (APC-resistance)
      involves examination of the phenotype and genotype of this thrombophilia. For
      examination of the phenotype coagulation and chromogenic tests are used. Their
      essence is examination in the presence and absence of exogenous APC. While the
      result of the original coagulation examination of APC-resistance which uses the
      APTT principle is influenced by a number of factors, the sensitivity and
      specificity of the modification of this examination (dilution of the examined
      plasma sample by FV deficient plasma before making the test) in relation to
      detection of FV Leiden is almost 100% and eliminates the majority of limitations
      of the original examination. The chromogenic assessment of APC-resistance has
      similar advantages, however, it cannot differentiate between the heterozygous and
      homozygous form of FV Leiden. During examination of the genotype of subjects with
      APC-resistance the mutation of FV Leiden is detected in as many as 90%. The group
      of subjects with the phenotype of APC-resistance comprises in particular subjects
      with acquired APC-resistance caused by conditions which lead to a disbalance
      between procoagulation and anticoagulation proteins of haemostasis which
      influence the reactions of the applied laboratory examinations. The acquired
      phenotype of APC-resistance can be also associated with an increased risk of
      thrombosis and the clinical manifestations of this thrombophilia resemble the
      classical, FV Leiden conditioned APC resistance. Rarely also congenital causes of
      the phenotype of APC-resistance are encountered caused by another mutation than
      the Leiden mutation of gene FV. The concurrent examination of the patient's
      plasma with the original and modified coagulation test makes it possible to
      assess the inborn cause of APC-resistance (positive finding also in modified
      examination). The presence of FV Leiden is then confirmed by examination of the
      genotype by the polymerase chain reaction.

PMID- 10951850
TI  - [Etiopathogenesis of type 2 diabetes mellitus].
AB  - In the genesis and development of type 2 diabetes in the great majority of
      subjects the contemporary lifestyle characterized by inadequate physical activity
      and an excessive energy intake is of basic importance. The majority of
      abnormalities and defects revealed by laboratory tests is probably secondary and
      caused by the above mentioned factors. Contemporary views of the etiopathogenesis
      of the disease are demotivating for patients: if the cause of their disease were
      an inborn disorder at the level of transmission of a signal on membranes then
      probably nothing else can be done than to take prescribed drugs. If the mistake
      involves the lifestyle, the latter can be changed and the disease avoided. Any
      medicamentous treatment is associated with the risk of undesirable effects--the
      complication of hyperinsulinism in treatment with sulphonyl urea derivatives and
      insulin or lactate acidosis after treatment with biguanides. This risk is not
      influenced by early prevention: dietary restraint and adequate physical exercise.
      Diabetes type 2 and 1--despite the common sign of hyperglycaemia--are
      characterized by a fundamental difference: (not influenced by treatment) DM type
      1 is characterized by enhanced catabolic processes, starvation at the cellular
      level. Type 2 is characterized by enhanced anabolic processes, excessive amounts
      of nutrients in cells. The authors submit recommendations which respect the
      secondary character of deviations for the development of DM 2 which can be
      detected by laboratory methods: The following are the basic etiopathogenetic
      mechanism for the development of DM 2: 1. Chronic excessive intake and inadequate
      output of energy a) increased nutrient supply to the liver with secondary
      increase of gluconeogenesis in the liver, b) chronic increased supply of glucose
      to peripheral tissues, in particular muscles and adipose tissue, inadequate
      physical exercise, with secondary restriction of nutrient supplies to these
      tissues. 2. Secondary affection of insulin secretion in the islets of Langerhans
      in the pancreas.

PMID- 10951851
TI  - [Hypokalemia, ventricular arrhythmia, ion channel defects, etc. Re: Conn syndrome
      and severe arrhythmia].

PMID- 10951852
TI  - [Hypertension and the kidneys].
AB  - The relationship between the kidneys and hypertension is multiple. Impaired renal
      function preventing adequate sodium excretion participates in the pathogenesis of
      primary hypertension. Renal diseases are the most frequent cause of secondary
      hypertension. Bilateral and unilateral parenchymatous affections predominate (5%
      of all hypertensions) over renovascular causes (2%). In the course of
      hypertension regardless of its etiology renal damage may develop-
      nephroangiosclerosis or atherosclerosis of the renal arteries with unilateral or
      bilateral affection (renal ischaemic disease). Hypertension is an important
      factor in progression of chronic renal diseases towards irreversible renal
      failure.

PMID- 10951853
TI  - [Renovascular hypertension].
AB  - Renovascular disease frequently escapes clinical diagnosis. Critical stenosis of
      the renal artery causes hypoperfusion of the kidney which in turn is the cause of
      renovascular hypertension and ischaemic nephropathy. Detection of renovascular
      disease in the population of hypertonic patients should be based on clinical
      symptoms. In a selected group one of the imaging methods can be used. The
      increasing number of patients with stenosis of the renal artery is indicated for
      percutaneous transluminal angioplasty or surgical revascularization as the
      function of the ischaemized kidney is a risk. Medicamentous treatment of
      hypertension, which is usually successful, is indicated in patients with
      atherosclerosis with a history of cardiovascular complications or a high risk of
      the latter. The contribution and risk of different therapeutic methods must be
      considered individually with regard to the clinical condition as well as the
      findings on the blood vessels. CONCLUSION: A unique contribution of angioplasty
      in stenosis of the renal artery or surgical revascularization is the possibility
      to improve renal haemodynamics and thus renal function. Prevention of ischaemic
      nephropathy calls for early diagnosis of renovascular disease.

PMID- 10951854
TI  - [Hypertension in hemodialyzed uremic patients].
AB  - The pathogenesis of hypertension in haemodialyzed uraemic patients is
      multifactorial. The following are involved: sodium and water retention as a
      result of the impaired excretory capacity of the kidneys, excessively increased
      activity of the RAAS and sympathetic nerve, increased levels of the vascular
      constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and
      reduced formation of vasodepressor factors. As to other factors in the
      development of hypertension raised intracellular calcium associated with
      hyperparathyroidism may participate, the stiffness of calcified arteries,
      erythropoietin treatment and preexisting essential hypertension. Treatment
      comprises salt restriction below 5 g/day, systematic control of the volume of
      extracellular fluid by ultrafiltration during every haemodialysis to the level of
      so-called dry weight and pharmacological treatment in patients where volume
      control dos not suffice. All drug groups are used. In their selection
      contraindications are taken into consideration as well as co-morbidity, the
      dialyzability of antihypertensive drugs and compelling evidence. In patients with
      a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta
      blockers are indicated in patients with IHD, in particular after IM. Calcium
      blockers are recommended in ventricular hypertrophy and diastolic dysfunction,
      when beta-blockers are contraindicated and in elderly patients. ACEI indicated in
      congestive heart failure and left ventricular hypertrophy with systolic
      dysfunction. Inhibitors of AT1 receptors are an alternative in case of
      undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used
      mainly in combinations. In case of failure the haemodialyzation method can be
      altered or changing the patients to CAPD may be considered. The relationship
      between BP and the survival of haemodialyzed patients is bimodal. An adverse
      effect is exerted by a high as well as low BP and in particular by
      interdialyzation hypotension. The target BP for the haemodialyzed population has
      not been defined so far. There is, however, evidence that a high BP is
      independently associated with the de novo development of IHD and MAP above 106 mm
      Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes
      the development and progression of left ventricular hypertrophy and MAP below 106
      mm Hg the development of heart failure. Long-term survival for 15 and more years
      is statistically significantly associated with MAP lower than 99 mm Hg.

PMID- 10951855
TI  - [Hypertension after kidney transplantation].
AB  - Hypertension is the most frequent non-rejection complication after
      transplantation of the kidney. It is encountered in 60 to more than 80% of
      recipients, depending on the investigated population and the definition of
      hypertension. It develops also in recipients who were normotensive before
      transplantation. While in dialyzed uraemic patients in the pathogenesis the most
      important part is played by hypervolaemia, after transplantation most frequently
      immunosuppressive treatment plays a part. The objective of our study was to
      assess the incidence of hypertension in the 1st and 2nd year after
      transplantation resp., the achieved blood pressure level (BP) the method of
      hypertension therapy in the group of recipients having immunosuppression
      treatment with corticoids, cyclosporin A (CyA) and mycophenolate mofetil (MFM).
      The group comprises 58 recipients of cadaverous renal grafts, 35 men (mean age
      44.4 +/- 10.7 years and 23 women (mean age 44.8 +/- 12.6 years). 53 recipients
      (91.4%) had a graft for the first time, 5 recipients (8.6%) had already a second
      renal transplantation. Thirteen men (37%) and 8 women (35%) had a functioning
      graft for at least two years. The blood pressure was assessed by the auscultation
      method during every ambulatory control examination, with the patient sitting, on
      the upper extremity on the contralateral extremity with an arteriovenous fistula.
      The rate of ambulatory check-up examinations depended on the time after discharge
      from hospital following transplantation: in the first month 1x a week, in the
      second to third month 1x in two weeks, from the 4th month usually once a month.
      The BP reading at the end of the first and second year resp. after
      transplantation was obtained by calculating the mean value of three consecutive
      readings: from the ambulatory check-up at the end of the 1st and 2nd year resp.
      after transplantation and the preceding and subsequent check-up examination.
      Hypertension was defined as a BP exceeding 130/85 mm Hg or a median arterial
      pressure (MAP) higher than 100 mm Hg. MAP was calculated from the mean value of
      the SBP and DBP according to the formula: MAP = DBP + 1/3(SBP-DBP).

PMID- 10951856
TI  - [Effect of ACE-inhibitors on changes in creatinine in the blood-- introduction].
AB  - In a retrospective study a total of 44 ambulatory examinations were made before
      enalapril was administered to 13 patients with essential hypertension and 52
      ambulatory examinations during enalapril treatment of these patients. All
      patients were followed up on a long-term basis: 1. without enalapril treatment (2
      24 months), 2. during enalapril treatment (4-24 months). For both investigation
      periods arithmetic means of plasma creatinine were calculated. The length of the
      investigation period was intentionally used as the sole criterium for inclusion
      in the group of patients. In nine patients during treatment the serum creatinine
      levels rose. The authors found a close positive correlation between the rise of
      plasma creatinine levels and the patients' age (correlation coefficient r = 0.59,
      n = 13, p < or = 0.02). Between the rise of creatinine (dependent variable) and
      independent variables (daily enalapril dose, initial creatinine blood level, the
      drop of the median arterial pressure during enalapril treatment) no close
      relationships were found. The rise of creatinine during enalapril treatment can
      be explained by a drop of the filtration pressure in the glomeruli during
      dilatation of the vas efferens. This drop of the filtration pressure was
      manifested by a slight increase of plasma creatinine only in patients with a drop
      of the renal perfusion (haemodynamic) reserve, i.e. in more advanced age groups.

PMID- 10951857
TI  - [Hypertension and diabetes mellitus--pathophysiology and risk].
AB  - The author submits a review on the combined prevalence of diabetes and
      hypertension which increases with age and is a basic risk factor of vascular
      cardiac and cerebral complications. It is associated with a higher incidence of
      obesity, hypertriglyceridaemia and reduced HDL-cholesterol. It is part of the
      metabolic syndrome X, the syndrome of insulin resistance. Hypertension is found
      in 60-80% type 2 diabetics and in 40% type 1 diabetics. Obesity is found on
      average in 40% type 1 diabetics and 85% type 2 diabetics. Macroangiopathy leads
      to ischaemic heart disease, cerebrovascular episodes and ischaemia of the lower
      extremities. British investigations revealed that long-term intensive control of
      the blood sugar level and hypertension reduced in particular the incidence of
      microvascular complications. A marked decline of the morbidity and mortality of
      diabetics was recorded after effective treatment of hypertension maintaining
      blood pressure readings below 130/80 mm Hg. The author discusses also
      contemporary views on the etiopathogenesis of hypertension in diabetic subjects
      who may suffer from different types of hypertension. The combination of diabetes
      and hypertension has obviously a multifactorial etiology--genetic predisposition
      and several external mechanisms. In the pathogenesis of hypertension an important
      part is played by insulin resistance and enhanced activity of the sympathetic
      nervous system. Reaven's hypothesis of metabolic syndrome X was supplemented in
      recent years by the role of the sympathoadrenal system. From the therapeutic
      aspect effective reduction of hypertension by correct selection of
      antihypertensives is most important.

PMID- 10951858
TI  - [Antihypertensives and their metabolic effects in diabetics].
AB  - Due to its frequent occurrence in diabetics, hypertension is a serious problem
      from the aspect of its effect on cardiovascular morbidity and mortality.
      Evaluation of metabolic and clinical effects of treatment of hypertension in
      diabetics should precede considerations on the selection of suitable
      antihypertensive treatment.

PMID- 10951860
TI  - [The effect of antihypertensive therapy on insulin resistance].
AB  - Insulin resistance is one of the main causes of diabetes mellitus type 2. This
      primary, genetically determined, by external environmental factors enhanced,
      reduced insulin effectiveness in target tissues (liver, muscle, adipose tissue)
      associated with compensatory hyperinsulinaemia is manifested by a prohypertensive
      effect. Secondary insulin resistance causes deterioration of diabetes
      compensation regardless of its type. It may have a number of causes and after
      their elimination it is fully reversible. Secondary insulin resistance can be
      influenced also by drugs. This fact must be born in mind when selecting
      antihypertensive treatment in diabetics.

PMID- 10951859
TI  - [Antihypertensives and their importance in the initial stages of diabetic
      nephropathy].
AB  - Diabetic nephropathy is a serious microangiopathic late complication of diabetes
      and is one of the most frequent causes of premature death of diabetic subjects.
      The main task of diabetologists and nephrologists in these patients is an attempt
      to arrest or at least delay progression of nephropathy. As to therapeutic
      possibilities, antihypertensive drugs are most suitable, i.e. angiotensin
      converting enzyme inhibitors, Ca blockers of the IInd generation and also
      blockers of AT1 receptors.

PMID- 10951861
TI  - [Results of the United Kingdom Prospective Diabetes Study and its importance in
      the treatment of hypertension in diabetics].
AB  - In 1997 the United Kingdom Prospective Diabetes Study (UKPDS), the largest and
      longest study in type 2 diabetes so far, was finished. Answers to fundamental
      questions of non-insulin dependent diabetes mellitus therapy were expected: 1.
      What is the benefit from a good metabolic control of diabetes? 2. Has any
      particular antidiabetic therapy advantages over the other ones? 3. What is the
      importance of concurrent antihypertensive therapy? The evidence was given that
      intensive therapy (with antidiabetics or insulin) substantially and significantly
      reduced the risk of microvascular complications, but the reductions of mortality
      and macrovascular complications were not significant. An adverse cardiovascular
      effect of sulfonylureas or insulin were not confirmed. All intensive therapeutic
      approaches reached comparable results only metformin appeared to be advantageous
      first-line therapy of choice in obese diabetics. The intensive control of
      hypertension proved to be even more effective in prevention both the
      microvascular and namely the macrovascular complications as well as in reducing
      diabetes related mortality.

PMID- 10951862
TI  - [Overview of the most important studies of hypertension and diabetes mellitus].

PMID- 10951863
TI  - [The role of home pressure monitoring in the treatment hypertension in the
      practice of general medicine].
AB  - AIM OF THE STUDY: The aim of the study was to evaluate home blood pressure (BP)
      measurement using an OMRON HEM 706 device (including printout values) for the
      treatment of essential hypertension by a greater number of general practitioners
      and to establish the incidence of "white coat hypertension". METHODS: We compared
      home BP values, taken by the portable digital Omron HEM 706 device with casual BP
      values, measured during the course of a 6-month treatment of essential
      hypertension by the ACE inhibitor perindopril or a combination of perindopril and
      a diuretic (most frequently a low dose of hydrochlorothiazide) in 503 patients
      with mild to moderate essential hypertension. Czech and Slovak general
      practitioners participated in the study. Home BP measurement was performed by the
      patients always during the 4 days preceding the visit by the general
      practitioner. Home BP was measured twice daily, "trough" and "peak" values (in
      the morning before the use of drug and then between noon and 2.00 p.m.), each
      time twice. The OMRON device enables to print out the measured values. Casual
      hypertension was defined as casual BP 140/90 mmHg and higher, "home hypertension"
      was defined as a mean BP higher than 130/85 mm Hg from 8 home BP measurements
      performed during the last 2 days before the visit by the general practitioner
      higher than 130/85 mmHg. RESULTS: A significant decrease in both systolic and
      diastolic BP occurred during the treatment by perindopril or the combination of
      perindopril and a diuretic. The decrease in BP was observed both in the casual BP
      values and in the home BP values. Normalisation of the casual diastolic BP
      (diastolic BP lower than 90 mmHg) occurred in 59.3% of the patients after the
      first month of treatment, in 75.4% of the patients after 3 months of treatment,
      and in 78.5% of patients after 6 months of treatment. Only 2.1% of patients
      dropped out from the study due to side effects. These data demonstrated a very
      good efficacy and tolerance of perindopril. Only 62.6% of general practitioners
      showing interest in home BP measurement at the informative meetings joined the
      study and 14-19% of patients of the whole studied group did not use home BP at
      all. In general the interest of general practitioners and their patients observed
      in this study was less than that observed among the cardiologists in our previous
      study. The incidence of the "white coat phenomenon" was related to its
      definition, it increased when using a less strict definition and decreased during
      the course of therapy, in parallel to the normalisation of BP. Home BP values
      were significantly higher during the first 2 day of measurement then during the
      last 2 days of measurement (of the 4-days period). "White coat hypertension"
      could be observed in 9.4% of the group during the study. Home BP measurement also
      enabled to disclose "white coat normotension" defined as normal casual BP values
      and hypertensive home BP values. "White coat normotension" occurred at the end of
      the study in 26.3% of the patients. This relatively high number of patients with
      "white coat normotension" could be partly due to a short period of rest at home
      before taking home BP values. CONCLUSION: Home BP measurement was positively
      evaluated both by the general practitioners and patients. Home BP measurement
      provides better information about the efficacy of hypertension treatment and
      discloses "overtreatment" ("white coat hypertension") as well "undertreatment"
      ("white coat normotension"). It also increases the adherence of patients to the
      treatment of essential hypertension. The interest in home BP measuring was,
      however, less among the general practitioners and their patients than among the
      cardiologists and their patients (observed in a previous study).

PMID- 10951864
TI  - [The level of diabetic compensation and endogenous secretion of insulin in newly
      diagnosed diabetics. Prospective study: Part 1].
AB  - In a prospective study of newly detected diabetic patients in 1989-1991 the
      authors focused their attention on the evaluation of blood sugar levels and HbA1c
      during manifestation of DM and the amount of insulin secretion in relation to
      diabetes type 1 and 2 in adult patients. Part 1 of the paper reveals great
      differences in the fasting blood sugar level during manifestation of DM (26% of
      the group had a blood sugar level lower than 8.5 mmol/l and 14% above 15 mmol/l)
      even after 1-4 months treatment (3.8-17.2 mmol/l). Similar differences were found
      in HbA1c values (4.5-12.9%). High C-peptide levels revealed an incorrectly
      assessed diagnosis of type 1 diabetes in 16.7% diabetics and low C-peptide values
      on fasting and postporandial values were at variance with the diagnosis of type 2
      diabetes in 6% of the group.

PMID- 10951865
TI  - [Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected
      clinical and laboratory indicators in multiple myeloma].
AB  - Hitherto conducted studies concerned with the problem of cytoadhesive molecules
      (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM).
      The subject of the submitted paper was evaluation of the relationship of soluble
      forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell
      adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and
      serum from a bone marrow aspirate (BMA) with selected clinical and laboratory
      indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of
      MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of
      plasmocytes in bone marrow, age, performance status, stage and substage of MM and
      activity of disease) and proliferation characteristics of myeloma plasmocytes.
      The authors analyzed two groups of patients with MM, a group of 64 examined in
      different stages of MM and a group of 39 examined when the diagnosis of MM was
      established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The
      sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of
      sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of
      sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180
      and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always
      somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and
      33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper
      normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518
      vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann
      Whitney's test, p0.05) revealed in both groups a significant relationship of both
      CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p
      0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed
      in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of
      the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64
      patients a relationship was found between sVCAM-1 in PBS and values of S
      creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2
      microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when
      evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients
      examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in
      PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in
      BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64
      patients there was no relationship between s-ICAM levels in PBS with any of the
      examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038)
      and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of
      MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the
      total group of 64 a relationship was found between sVCAM-1 in PBS with the
      patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39
      patients a relationship between sVCAM on PBS and the substage of MM (p -0.031).
      On analysis of sICAM-1 a relationship was found between levels in BMA only with
      the patient's age (p -0.015). From the investigation ensued that despite evidence
      of a number of correlations between sVCAM and sICAM-1 levels and clinical and
      laboratory indicators of MM no relationship was found which could be applied
      under conditions of clinical practice. Assessment of levels of different
      indicators in serum of bone marrow aspirate did not reveal any advantages over
      examination in peripheral blood serum.

PMID- 10951866
TI  - [The effect of ambulatory nutritional intervention using defined enteral
      nutrition on the nutritional status of selected adult patients with cystic
      fibrosis].
AB  - The prevalence of mild and serious nutritional disorders in patients with cystic
      fibrosis is high. One of the possible ways how to supplement the necessary
      nutrients is the administration of defined supplementary enteral nutrition. The
      objective of the presented work is to evaluate the effect of supplementary
      domiciliary enteral nutrition in adult patients with cystic fibrosis. To eight
      patients with cystic fibrosis, mean body weight 51.77 +/- 10.63 kg, mean age 24.7
      +/- 1.9 years for a period of 6 +/- 1 months enteral nutrition was administered
      (containing 40 and 55.1% energy as fat) with a caloric density of 10 kcal/kg as
      supplementary domiciliary nutrition. The mean body weight increased from 51.77 +/
      10.63 to 53.13 +/- 10.59 kg (p < 0.02), the mean skinfold thickness increased
      from 7.98 +/- 6.04 to 8.65 +/- 6.30 mm (p < 0.05) and the mean serum albumin
      concentration increased from 33.66 +/- 0.97 to 37.29 +/- 3.33 g/l (p < 0.05). No
      undesirable side-effect associated with the administration of enteral nutrition
      were observed. The nutritional intervention by domiciliary enteral nutrition
      produced no undesirable side-effects and led to a statistically significant
      improvement of parameters of the nutritional status.

PMID- 10951867
TI  - [Silent forms of hereditary spherocytosis].
AB  - We report 7 cases of "silent" form of hereditary spherocytosis observed among
      members of 4 different families. Silent form of hereditary spherocytosis occurred
      in 5.4% of all patients with hereditary spherocytosis treated in our institute.
      The patients with silent form featured normal Hb level and red blood cell count,
      normal or slightly elevated reticulocyte count and bilirubin level. Osmotic
      resistance of red blood cells was decreased and autohemolysis was increased,
      nevertheless, the differences from normal range were less prominent than in
      patients with manifest form of the disease. Analysis of red cell membrane
      revealed deficiency of band 3 protein in all cases of silent form of hereditary
      spherocytosis.

PMID- 10951868
TI  - [Serum neopterin in IgA deficiency and common variable immunodeficiency].
AB  - Serum neopterin levels were determined in 31 children and 18 adults with the
      selective IgA deficiency and in 17 adult patients with a common variable
      immunodeficiency. The results were compared with serum neopterin levels of 41
      children and 26 adult controls. All sera were obtained in an infection-free
      period. We observed significantly increased serum neopterin levels in common
      variable immunodeficiency patients; this increase was observed namely in patients
      with a severe course of the disease. No increase in serum neopterin levels was
      observed neither in IgA deficient patients prone to respiratory tract infections
      nor in IgA deficient persons examined for other reason (allergy, rheumatoid
      disease, etc.). The results stand against macrophage activation in the selective
      IgA deficiency.

PMID- 10951869
TI  - [Paget's disease of bone--treatment with alendronate, calcium and calcitriol].
AB  - In the submitted case-history the authors describe the clinical picture,
      diagnosis and treatment of the non-complicated form of Paget's disease in a 68
      year-old patient with typical X-ray findings on the vertebrae, pelvis and left
      tibia. The laboratory findings revealed liminal alkaline phosphatase (ALP)
      values, 2.5 times raised values of the aminoterminal telopeptide of collagen I in
      the organic bone matrix (NTx) in the 24-hour diuresis and slightly elevated
      osteocalcin (OSCA) levels. The finding of whole-body skeletal scintigraphy was
      atypical and thus was no diagnostic asset. Aimed transiliacal bone biopsy
      according to Bordier taken from the pathological focus confirmed the diagnosis of
      morbus Paget. The patient was treated for six months with the following
      preparations: Fosamax (monosodium alendronate tablets a 10 mg, Merck Sharp and
      Dohme, USA) 1 tablet per day, Vitacalcin (calcium carbonate, tablets a 250 mg
      elemental calcium, Slovakofarma, Slovak Republic) 2 x 1 tablet per day, Rocaltrol
      (calcitriol tablets a 0.25 ug, Hoffman La Roche, Switzerland) 1 tablet on
      alternate days). Because of gastrointestinal complaints the authors did not
      administer 40 mg alendronate per day, as recommended in the American literature.
      Based on the laboratory finding of normalization of the bone turnover, reduction
      of the number of osteoplastic foci on the X-ray image of vertebrae and pelvis,
      regression of the vertebrogenic algic syndrome and improved mobility of the
      patient, the authors consider the 6-month administration of alendronate, 10 mg
      per day, calcium carbonate and calcitriol therapeutically effective and
      successful.

PMID- 10951870
TI  - [Diagnosis and treatment of pancreatic islet cell tumors producing vasoactive
      intestinal polypeptide (VIPoma)].
AB  - The incidence of VIPoma is approximately one per 10 million population. Thus in
      the Czech Republic this rare disease should be diagnosed once per year. The
      authors present their experience with the diagnosis and treatment of patient born
      in 1956, who suffered since 1990 from diarrhoea, at first episodically. In 1992
      1994 the diarrhoea was profuse, caused dehydration, hypokalaemia and severe
      metabolic acidosis without an increase of the anion gap. As a result of
      dehydration the patient developed acute renal insufficiency. Due to hypokalaemia
      he developed paroxysmal atrial fibrillation. The diagnosis was based on the
      clinical finding and later confirmed on laboratory examination by a high VIP
      serum concentration. For treatment of diarrhoea Sandostatin was used. The tumour
      was located only after a scan with 123I-VIP in the cauda of the pancreas.
      Scintigraphy with labelled octreotide, similarly as other imaging methods (sono,
      X-ray and CT) were not effective. In 1994 left-sided hemipancreatectomy was
      performed. Although the patient was operated four years after the onset of the
      disease, no secondaries were detected. After surgery the diarrhoea stopped and no
      further treatment was necessary.

PMID- 10951871
TI  - [Sexual activity and the cardiovascular system in health and disease. Use of
      sildenafil in heart patients].
AB  - Sexual intercourse involves mild to medium severe physical exertion of the
      cardiovascular system. The risk of sudden death associated with sexual activity
      is very low, and so is the risk of developing infarction. In patients with pre
      existing ischaemic heart disease sexual activity is safe in case of controlled
      angina with tolerance of a medium-grade load on examination on a treadmill. After
      acute myocardial infarction with a non-complicated course sexual activity can be
      resumed in a familiar environment with a familiar partner after about 10 days. In
      stabilized anginous patients sildenafil administration is safe assuming that the
      patient does not take long-acting nitrates and does not need frequent
      administration of short-term acting nitrates. It is important to avoid nitrates
      also in the treatment of acute ischaemic conditions in these patients. At present
      we do not possess adequate information on the clinical importance of influencing
      sildenafil elimination by competition with other substances excreted by the same
      route.

PMID- 10951872
TI  - [The paradox of insulin resistance].
AB  - Insulin resistance (IR) is a phenomenon which associates several serious
      "diseases of civilization" within the framework of Reaven's metabolic syndrome.
      In the submitted paper the authors describe the so-called "paradox of insulin
      resistance"--a paradoxical finding of inadequate insulin action under laboratory
      induced conditions while under "common" conditions the finding is reversed.
      Diabetes mellitus type 2 (with obesity) is characterized by excessive filling of
      cells by energetically rich substances. A low energy output, inadequate physical
      activity in these subjects leads to the development of regulatory mechanisms,
      which restrict further nutrient (glucose) uptake from blood into cells. During
      subsequent stages of the disease the excessive glucose uptake by adipose tissue
      cells and muscle is ensured by the high concentration gradient, hyperglycaemia
      and hyperinsulinaemia. Induction of "comparable" conditions in clamp studies
      leads to paradoxical results. During relative hypoglycaemia and hypoinsulinaemia
      (as compared with normal conditions) the tissues of the diabetic patient, due to
      regulatory mechanisms, take up a smaller amount of glucose than tissues of non
      diabetic subjects (although under normal conditions the glucose uptake is
      higher). This phenomenon is called "Paradox of insulin resistance". In a major
      proportion of patients IR can be induced by mere maintenance of
      hyperinsulinaemia, it can be minimalized by reducing the nutrient intake and by
      increasing physical exertion. Differentiation of patients where IR is a
      secondary, regulatory phenomenon is one of the basic tasks of the physician. Only
      patients who suffer from primary disorders of insulin function, primary IR and
      true insulin deficiency should be treated by administration of hyperinsulinaemia
      inducing drugs. It is questionable how suitable it is to administer these drugs
      to patients who suffer from a life-style disorder and are threatened by
      complications associated with hyperinsulinism.

PMID- 10951874
TI  - [The renin-angiotensin-aldosterone system and serum lipoproteins in patients with
      essential hypertension].
AB  - The authors investigated the relationship between the activity of the renin
      angiotensin-aldosterone system and serum lipid levels in patients with essential
      hypertension (EH). They examined 72 patients with EH stage I and II WHO
      classification (group A, n = 72, age bracket 16-70 years). They investigated the
      plasma renin activity (PRA), plasma aldosterone (PA) and total cholesterol (TCH),
      HDL, LDL cholesterol and triglycerides (TG). They divided the group into three
      sub-groups according to the PRA into low (L), normal (N) and high renin groups
      (H) In the whole group they did not find significant differences in the lipid
      levels in relation to PRA. They selected from the group patients older than 40
      years (group B) and in those they recorded significantly higher TCH levels in
      group H as compared with normal (N) (p < 0.05) and L (p < 0.05) and significantly
      higher LDL levels in group H as compared with L (p < 0.01). They found a
      significant direct relationship between PRA and TCH (p < 0.05) and between PRA
      and LDL (p < 0.01), a liminal relationship between PA and TCH (p = 0.05). They
      did not find a significant relationship between the RAAS activity and HDL or TG.
      The authors conclude that patients with EH above 40 years and high PRA a markedly
      greater hyperlipoproteinaemia as compared with the low- or normal-renin group.
      This may partly explain the higher incidence of cardiovascular complications in
      high-renin EH reported by some authors.

PMID- 10951873
TI  - [Correction of morphology and indicators of atrial function using long-term
      physiologic cardiac pacing in patients with prior chronic atrioventricular
      dissociation or VVI pacing].
AB  - In patients with atrioventricular dissociation associated with complete
      atrioventricular block or reverse synchronization and preservation of the sinus
      rhythm the atria are mechanically over-burdened by contraction in an inept stage
      of the cardiac cycle (against a closed atrioventricular valve). Prolonged
      overburdening leads to dilatation of the atria and a higher incidence of
      supraventricular arrhythmias incl. atrial fibrillation. The objective of the
      trial was to assess whether these changes are reversible. METHOD: In 26 patients
      where atrioventricular dyssynchronization as the only detectable reason of atrial
      dilatation was eliminated by implantation of sequential atrioventricular
      stimulation, the authors investigated by echocardiography the dimensions, volumes
      and ejection fractions of the atria and left ventricle at baseline (A), after 24
      hours following implantation (B), after 8 weeks (C), after one year (D). RESULTS:
      Left atrium: during the first 24 hours diminution in the long axis occurred (AxB:
      -4.28, p = 0.023), the difference remained significant even after eight weeks
      (AxC: -6.1, p = 0.050). The ejection fraction was after eight weeks also
      significantly greater (BxC: +8.29, p = 0.039). Right atrium: within 24 hours the
      long axis was reduced (AxB: -4.70 p = 0.033), the difference was apparent also
      after 8 weeks (AxC: -5.60 p = 0.028). Within 8 weeks (AxC) the mean enddiastolic
      pressure diminished significantly (-11.01, p = 0.032) as well as the endsystolic
      volume (-9.01, p = 0.018, while the ejection fraction increased (+7.50, p =
      0.031). The right ventricular volume during diastole increased between the 8th
      week and the check-up after one year (+6, -1, +17.77, p = 0.046). Left ventricle:
      the ejection fraction had a rising trend, after one year a significant difference
      was found as compared with the baseline value (AxD: +10.20%, p = 0.007) and as
      compared with the value assessed 8 weeks after implantation (CxD: +9.44%, p =
      0.018). The change of the ejection fraction was inversely proportional to the
      value of the ejection fraction immediately after implantation (r -0.83, p <
      0.01). CONCLUSION: The authors provided evidence of the reversibility of the
      morphological and functional atrial damage and the favourable effect of
      atrioventricular synchronization on left ventricular function.

PMID- 10951875
TI  - [Effect of long-term hypolipidemia therapy on diastolic filling of the left
      ventricle].
AB  - In 18 patients with hypercholesterolaemia (total cholesterol > or = 6.7 mmol/l or
      LDL > or = 4.0 mmol/l a standard and Doppler echocardiographic examination was
      made before and after 27 +/- 7 months hypolipidaemic treatment leading to a drop
      of the cholesterol levels of at least > or = 1 mmol/l. Except for
      hypercholesterolaemia these patients did not suffer from any diseases with an
      impact on cardiac activity. Doppler echocardiography was used to measure
      parameters of diastolic left ventricular filling at rest and during 2-4 minutes
      of an isometric load. Lipid lowering therapy led to a significant drop of the
      deceleration half-time of early diastolic filling of the left ventricle at rest
      (from 88 +/- 16 ms to 74 +/- 15 ms, p < 0.01) as well as during an isometric load
      (from 83 +/- 31 ms to 61 +/- 31 ms, p < 0.05). The authors observed an
      insignificant increase of the rate of early diastolic left ventricular filling at
      rest (from 53 +/- 10 cm/s to 60 +/- 10 cm/s, p = ns) and during an isometric load
      (from 52 +/- 11 cm/s to 56 +/- 18 cm/s, p = ns). Similarly there was also an
      insignificant increase of the ratio of the velocity of left ventricular filling
      in early diastole to the rate of filling during atrial contraction (from 1.02 +/-
      0.27 to 1.10 +/- 0.33 at rest and from 0.91 +/- 0.25 to 0.93 +/- 0.41 during a
      load, both p = ns). It may be concluded that long-term hypolipidaemic treatment
      in patients with hypercholesterolaemia contributes to better diastolic filling of
      the left ventricle.

PMID- 10951876
TI  - [Reactions to metals in patients with chronic fatigue and autoimmune
      endocrinopathy].
AB  - Our study was designed to assess the effect of heavy metals on the severity of
      fatigue in autoimmune thyroid disease associated with autoantibodies against
      other endocrine organs. We compared our data with those obtained from other
      groups of patients. A total of five groups of patients were examined by their
      medical history, dental examination, and using a modified test of blast
      transformation of metals (Melisa): a) 10 fatigues female patients with autoimmune
      thyroidism and polyglandular activation of autoimmunity, b) 12 fatigued patients
      with autoimmune thyroidism, c) 28 fatigued patients free of endocrinopathy, d) 22
      professionals without evidence of autoimmunity, e) 13 controls, a population
      sample, the individuals did not complain of marked fatigue and their laboratory
      tests did not show signs of autoimmunity and endocrinopathy. Fatigue regardless
      of the underlying disease is primarily associated with hypersensitivity to
      inorganic and organic mercury, nickel, and gold. The groups differed in their
      hypersensitivity to other metals. In the control group, hypersensitivity--mostly
      to cadmium and lead--was found in four of the examined individuals only.
      Statistical analysis of data obtained from professionals and controls revealed a
      higher incidence of positivity to organic and inorganic mercury and nickel in
      professionals.

PMID- 10951877
TI  - [Basal autonomic tone in patients with vasovagal syncope].
AB  - Autonomic nervous mechanisms play an important part in the pathogenesis of
      vasovagal syncope. The objective of the submitted work was investigation of the
      autonomic tone in patients with vasovagal syncope. The authors examined a group
      of 39 patients with vasovagal syncope (patients with a positive head-up tilt test
      (HUT) from a group of patients with syncopes of unknown origin--12 men, 27 women,
      mean age 34 years), a control group of 21 patients with negative HUT from the
      group of patients with syncope of unknown etiology (11 men, 10 women, mean age 32
      years) and a control group of 14 healthy subjects without history of syncope (14
      men, mean age 26 years). The autonomic tone was evaluated on the basis of
      statistical and spectral analysis of heart rate variability. The basal autonomic
      tone in patients with vasovagal syncope does not differ from that in normal
      subjects. The increased vagal tonus probably is not a predisposing moment for the
      development of vasovagal syncope. Assessment of the basal autonomic tone does not
      make prediction of the results of the head-up tilt test possible.

PMID- 10951878
TI  - [Clinical aspects of Chlamydial infection].
AB  - Chlamydiae are one of the most widespread pathogens of man, though up to 90% of
      infected people have few or no symptoms. This bacterial pathogen has been shown
      to cause respiratory track infections, pelvic inflammatory disease and articular
      diseases. We explored group of 20 patients with the elevated anti-chlamydial
      antibody titres and clinical significance of infection. All patients were also
      taking a tree-week course of antibiotics therapy.

PMID- 10951880
TI  - [The stress ergometry test in diabetics and non-diabetics].
AB  - OBJECTIVE: Evaluate risk factors of ischaemic heart disease (IHD) and the
      importance of burdening on a bicycle ergometer (BE) in the diagnosis of IHD in
      diabetic and non-diabetic subjects. CHARACTERISTIC OF GROUP: The authors
      evaluated in a retrospective study all 308 patients subjected to BE during the
      period 11/98-1/99 in Konstantinovy Lazne. Characteristics of diabetic vs. non
      diabetic subjects: number (97 vs. 211), men (70.1 vs. 70.14%) mean age (59.76 vs.
      58.01), height (1.71 vs. 1.71 m), body weight (85.91 vs. 81.40 kg), BMI (29.36
      vs. 27.68 g/m2), total cholesterol (5.73 vs. 5.51 mmol/l,) triacylglycerols (2.63
      vs. 2.08 mmol/l), fasting blood sugar level (7.31 vs. 4.88 mmol/l), hypertension
      (24.74 vs. 37.44%), hyperuricaemia (40.21 vs. 27.01%), IHD (93.81 vs. 93.84%),
      ischaemia of the lower extremities (6.19 vs. 13.74%), cerebrovascular episodes
      (7.22 vs. 5.21%), smokers 10.31 vs. 5.21%), ex-smokers (47.42 vs. 57.82%), non
      smokers (42.27 vs. 36.97%). The diabetic patients were treated in 31.96% with
      PAD, in 5.15% with insulin and in 62.89% by diet only. EVALUATION: BE was used to
      assess and set the load tolerance, i.e. with regard to the current medication.
      The conclusion of BE is from the aspect of IHD either positive (ECG signs of
      coronary insufficiency), negative (without signs of coronary insufficiency at the
      level of 85% aerobic capacity according to Astrand) or impossible to evaluate
      (without signs of coronary insufficiency, while not attaining this level of
      load). Positive ergometric examinations were divided into symptomatic ones (i.e.
      with stenocardias during BE) and asymptomatic (silent ischaemia). In diabetic vs.
      non-diabetic subjects there were 0% vs. 6.16% symptomatically positive BE, 27.84%
      vs. 11.37% positive BE with silent ischaemia, 17.53% vs. 20.85% negative BE and
      54.64% vs. 61.61% BE which could not be evaluated. The watt training tolerance
      was 51.55 vs. 57.26 W. CONCLUSIONS: In diabetics (31.49% of the group) there was
      a significantly higher body weight, BMI, TG. As to risk factors of IHD and
      manifestations of atherosclerosis there were among diabetics more patients with a
      history of a cerebrovascular episode, more smokers and conversely fewer
      hypertonic subjects and fewer with ischaemia of the lower extremities than in non
      diabetic subjects. During BE in diabetics there were more silent ischaemias than
      in non-diabetics. None of the diabetics with a positive BE suffered from
      symptomatic ischaemia. The high percentage of BE which cannot be evaluated in
      both groups is due to the concurrent administration of drugs, in particular beta
      blockers and the protocol of the examination (an increasing loading test after 4
      min. a 25 W) which is suitable for setting the training load and not for
      assessment of coronary insufficiency (for this purpose the protocol after 2 min.
      a 50 W is more suitable). In the conclusion the authors evaluate the importance
      and informative value of different diagnostic examinations for detection of IHD
      or its severity in diabetic and non-diabetic subjects.

PMID- 10951879
TI  - [The effect of body weight on insulin activity].
AB  - Insulin resistance is found patients with diabetes mellitus type 2 as well as in
      obese subject without diabetes. The objective of our investigation was to compare
      the action of insulin in morbidly obese subject with and without diabetes and in
      diabetic subject with different degrees of obesity. A total of 36 diabetic were
      examined, divided according to the BMI into morbidly obese (DMTO: BMI > 40 kg/m
      2.n = 6) those with medium severe obesity (DMSO: BMI 31-40 kg.m-2.n = 16), with
      slight overweight DMLO. BMI 26-91 kg.m-2.n = 9) and non-obese diabetics (DMBO).
      BMI 21-26 kg.m-2.n = 5). The group of morbidly obese non-diabetic subject (NDTO,
      BMI > 40 kg.m-2.n = 5) and non-obese healthy subject (C, BMI < 26 kg.m-2, n = 12)
      served as control. All examined subject were of similar age the diabetic subject
      had similar values of indicator of diabetic control (HbA1c was 7.1 +/- 0.5%). The
      examination was made using the method of an isoglycaemic hyperinsulinaemic clamp
      on a Biostator at an insulin infusion rate of 1mU.kg-1.min-1 for a period of 20
      minutes. The results of the index of tissue sensitivity to insulin revealed a
      markedly deteriorated action of insulin in morbidly obese diabetes and non
      diabetics in relation to control group of healthy slim controls (M/I, DMTO: 12.4
      +/- 7.3 and NDTO: 9.2 +/- 4.1, p < 0.001, mumol.kg-1.min-1 na mU.l-1 x 100), in
      midly and medium obese diabetics the insulin resistance was of difference grades
      (M/I, DMLO: 34.2 +/- 9.3, p < 0.05, and DMSO: 25.9 +/- 18.5 p < 0.001 mumol.kg
      1.min-1 na mU.l-1 x 100. Non-obese diabetic and non-diabetic subject had a normal
      insulin action (M/I, DMBO: 58.3 +/- 29.4 and C: 48.9 +/- 5.0 mumol.kg-1.min-1 per
      mU.l-1 x 100. The metabolic glucose clearance differed however between diabetic
      and non-diabetic subject (MCRG, DMTO: 2.0 +/- 0.4, p < 0.001, DMSO: 3.8 +/- 2.4,
      p < 0.001, DMSO: 5.4 +/- 1.7, p < 0.05 v.s. C: 8.6 +/- 1.1 and NDTO: 3.8 +/- 1.5,
      p < 0.001 ml.kg-1.min-1). The statistical significance is related to the control
      group of slim healthy subject. From this ensues that no significant difference
      was found between slim diabetic and non-diabetic subjects in the majority of
      parameters expressing the action of insulin with the exception of the metabolic
      glucose clearance. At the same time the authors found in the whole group of 53
      examined subject a statistically significant correlation between the BMI and the
      index of tissue sensitivity for insulin (M/I) (r = -0.55, p < 0.001). On
      examination of characteristics of insulin receptors on erythrocytes the authors
      found a reduced number in diabetic subject as compared with the two control
      groups (p < 0.05). It may thus be concluded from this investigation that the BMI
      has a decisive role in the action insulin.

PMID- 10951881
TI  - [Personal experience with therapeutic plasmapheresis using the AS.TEC 204
      separator].
AB  - The authors experience with Fresenius AS.TEC 204 separator for therapeutic
      exchange plasmaphereses in patients with different diagnoses. The describe the
      technique of separation, evaluation of advantages of the apparatus. Minor
      modifications made by the author improve the process of separation. Although the
      apparatus does not make erythrophereses possible so far, it proved useful for
      exchange plasmaphereses.

PMID- 10951882
TI  - [Erythema exsudativum multiforme with macroglobulinemia].
AB  - A case of a 47-year-old man with skin lesions of erythema multiforme and
      macroglobulinemia is reported. Histological changes corresponded with mixed
      dermoepidermal type of erythema multiforme and direct immunofluorescence showed
      fibrillar band with anti-IgM and anti-fibrin on basement membrane. Further
      examination revealed serum monoclonal IgM kappa with traces in urine. Association
      or coincidence of these findings is discussed.

PMID- 10951883
TI  - [Hypertension after heart transplantation].
AB  - Transplantations of the heart are in recent years the therapeutic method in
      severe cardiac failure. One of the complications in the long-term follow-up of
      patients is the development of hypertension. The incidence of hypertension in
      patients treated with cyclosporin and prednisone is 70-90%. In the development of
      hypertension participates in addition to classical mechanisms (renin angiotensin
      system, fluid volume and peripheral resistance) also the negative effect of
      cardiac denervation, cyclosporin immunosuppression, corticoids and nephropathy.
      The nocturnal drop of pressure and pulse rate is lacking. Mechanisms of
      cyclosporin induced hypertension:enhancement of the vasoconstricting effect of
      endothelin 1, reduced NO production, activation of neurohumoral vasoconstrictors,
      increased calcium level in cytosols, increased thromboxane A production, reduced
      production of vasodilatating prostaglandins and activation of the sympathicus.
      The prerequisite of treatment are efforts to maintain the lowest possible
      effective cyclosporin level and if possible discontinue corticoids during the
      first year. The drug of first choice are calcium antagonists among others for
      their preventive effect on the vasculopathy of the graft. Other recommended
      groups of drugs are ACE inhibitors and diuretics.

PMID- 10951884
TI  - [Hyperglycemia and atherosclerosis. Causal relation or association?].
AB  - Hyperglycemia may lead to atherosclerosis by different pathogenic mechanisms.
      Nonenzymatic glycation and oxidation of LDL may increase its atherogenicity.
      Glycation may modify some arterial wall structural proteins. Increased blood
      glucose leads to hypertriglyceridemia which results in decrease of HDL
      cholesterol level and in increase of atherogenic dense LDL particles.
      Hyperglycemia also adversely affects processes of platelet aggregation,
      hemocoagulation and fibrinolysis. It accelerates the development of diabetic
      nephropathy--a condition with a high prevalence of macrovascular diseases.
      Prospective epidemiologic studies have shown that diabetic patients in worse
      metabolic control had an increased cardiovascular morbidity and mortality.
      Therapeutic randomized studies in type 1 (DCCT) and type 2 (UKPDS) diabetic
      patients have shown that better diabetes control had a preventive effect against
      development of microvascular complications. The incidence of macrovascular
      complications both in type 1 diabetic patients on intensive insulin or
      sulfonylurea treatment has been decreased on the level of borderline statistical
      significance. Metformin lead to a significant decrease in myocardial infarction
      incidence in the subgroup of obese type 2 diabetic patients. In conclusion,
      maximal possible metabolic control of diabetes prevents the development of
      microvascular complication, but more impressive decrease in macrovascular disease
      incidence probably requires to affect another important risk factors for
      atherosclerosis, such as dyslipidemia and hypertension.

PMID- 10951885
TI  - Cytokines: regulators of eosinophilic inflammation.
AB  - Cytokines are glycoproteins that are secreted and that regulate immunologic
      inflammation. The cytokine system is characterized by much redundancy and cross
      reactivity. Of the more than 100 cytokines that have been identified, interleukin
      5 (IL-5) and the chemokine (chemotactic cytokine), eotaxin, are the most
      selective for cells of eosinophilic origin. Because of this relative specificity,
      and because of their important immunoregulatory roles, IL-5, eotaxin, and their
      receptors IL-5R and CCR3 are potential targets for non-glucocorticosteroid
      pharmacological treatment of eosinophilic inflammation.

PMID- 10951886
TI  - An updated model of cell-mediated immunity--listeriosis: clinical and research
      aspects.
AB  - Listeria monocytogenes causes sepsis and meningitis in immunocompromised hosts
      and a devastating maternal/fetal infection in pregnant women. In recent years a
      more benign gastroenteritis in normal hosts has been described. Listeria has been
      increasingly identified as a food-borne pathogen, and large-scale contamination
      of processed foods with resulting outbreaks has occurred in recent years,
      possibly as a result of consolidation of the food industry. Experimental
      listeriosis in mice has proven to be an extraordinarily useful model for
      analyzing cell-mediated immune host defenses. Contrary to original concepts, we
      found that neutrophils, not macrophages, are the prime effectors during early
      infection. CD8+ T cells are then responsible for lysing infected hepatocytes
      through perforin-related (early primary and secondary infection) or Fas-L/Fas
      mechanism (late primary). Of interest, non-classical MHC class Ib restricted
      recognition mechanisms exist early, whereas MHC class Ia mechanisms can be
      detected throughout infection.

PMID- 10951887
TI  - Immunomodulation and allergy.
AB  - A major function of the immune system is to protect the body from infection and
      the diseases caused by infectious agents. The immune system also provides
      protection against cancer cells, for once they arise, cancers can essentially
      behave as "foreign" cells capable of causing pathology. In contrast, allergy is a
      manifestation of the immune response to certain environmental cells or molecules
      that are usually neither a threat for infection nor cancer. Allergic reactions
      are generally an annoynance, even life-threatening. I will focus on type I
      allergy, characterized in part by induction of IgE antibody responses to
      allergens. It should be noted that not all IgE responses cause allergic symptoms.
      There is even evidence that IgE responses to tropical helminthic parasites offer
      a degree of immunity to reinfection. I have three objectives: (1) review T cell
      differentiation leading to the Th1/Th2 paradigm; (2) evaluate the increased
      prevalence of atopy, including asthma, as a consequence of a Th2-dominated immune
      system; (3) relate the high prevalence of asthma in inner city United States
      black children to the relatively recent migration of their ancestors from
      tropical regions of Africa, where genetically biased Th2-dependent IgE responses
      may be important in protection against high burdens of parasitic worms.

PMID- 10951888
TI  - IgE and the allergy-asthma connection in the 23-year follow-up of Brown
      University students.
AB  - The Hygiene Hypothesis helps to explain the increased epidemiology of atopy,
      especially asthma and hay fever. This hypothesis depends on two major
      immunological pathways, the Th1 and the Th2 pathways, which are mutually
      inhibitory, with the Th2 pathway being the dominant one in fetal life and the
      newborn. The Th1 leads to a cellular delayed hypersensitive response while the
      Th2 pathway leads to increased IgE, eosinophilia, atopy, and
      airway/hyperresponsiveness. The ever-increasing vaccines for immunization against
      viral and bacterial microorganisms together with better public health hygiene
      procedures introduce a bias in favor of the inhibition of the Th1 pathway,
      thereby allowing the Th2 pathway, with its IgE hypersensitivity, to predominate.
      We have attempted to correlate this new hypothesis with data from our Brown
      University college student longitudinal study. In this study, our data have
      demonstrated that allergen sensitization (positive pollen skin tests reactions)
      leads to an increased risk factor for developing asthma. Most of our asthmatic
      patients in our longitudinal study had positive allergy skin tests. Also,
      students born in months with high concentrations of atmospheric ragweed pollen
      had an increased risk of developing sensitization to ragweed and later to develop
      hay fever, which may lead to asthma. There is a strong association of asthma with
      hay fever (a classic IgE disease). Also, hay fever patients have three times the
      risk for developing asthma than controls. There appear to be several factors
      needed to express the phenotype of allergic asthma: elevated IgE, eosinophilia,
      airway hyperresponsiveness, exposure to allergens, and the predominance of the
      Th2 pathway of immunologic reactions.

PMID- 10951889
TI  - Allergy and asthma: classic TH2 diseases (?).
AB  - More than a decade of cytokine immunology has revealed a central role for pro
      allergic TH2-like cytokines in the immune pathogenesis of allergic diseases and
      asthma. Of these, IL-4, IL-5, and IL-13 are produced mostly by T lymphocytes;
      more recently, numerous other immune cell types have been found capable of
      producing these cytokines as well, although their role in mediating atopic
      disease pathogenesis is less well understood. In contrast, the counterregulatory
      cytokine IFN-gamma can inhibit both the production and activities of the pro
      allergic cytokines; therefore, central to the atopic diseases is a paradigm of
      cytokine imbalance, with overproduction of the TH2-like cytokines, and a relative
      deficiency of IFN-gamma production. Intriguing recent evidence is that all humans
      are TH2-like cytokine "skewed" at birth, due to maternal-fetal immune biology
      imperatives. However, further investigations suggest that IFN-gamma is likely to
      be pro-inflammatory in many if not most aspects of chronic allergic inflammation.
      Therefore, our understanding of these "classic TH2" diseases evolves, with
      important insights that will serve to optimize therapeutic strategies and
      investigations in the new millennium.

PMID- 10951890
TI  - The "Peter Pan" syndrome and allergy practice: facilitating adherence through the
      use of social support.
AB  - The complexity of care of some patients in an allergy-immunology practice may be
      increased by behavioral abnormalities of the patients. Facilitating adherence
      through the use of social support may be the most effective treatment strategy
      for some of the most difficult of these patients. We report three patients whose
      medical management problems were alleviated largely because of the participation
      of their support system. All three patients were stabilized because of the
      acceptance of responsibility and support of the physician by the designated
      member of the patient's support system. The range of social support used to
      manage nonadherent patients ranged from directly providing instructions to a
      family member to the consistent presence of a spouse or companion at multiple
      clinical visits. In all cases, the success in management was attributed largely
      to the presence of a support system.

PMID- 10951891
TI  - Efficacy and safety of nedocromil sodium 2% ophthalmic solution b.i.d. in the
      treatment of ragweed seasonal allergic conjunctivitis.
AB  - The efficacy and safety of twice-daily nedocromil sodium 2% ophthalmic solution
      and vehicle were compared in the treatment of ragweed seasonal allergic
      conjunctivitis. Two separate multicenter, randomized, double-masked, placebo
      controlled studies were subjected to a combined analysis. Following a one-week
      baseline period during the beginning of the ragweed pollen season, 189 patients
      with seasonal allergic conjunctivitis received either nedocromil sodium or
      vehicle b.i.d. for eight weeks. Efficacy was evaluated by patient diary cards and
      clinical eye examinations. Safety was assessed by reports of adverse events.
      Compared with vehicle, nedocromil sodium produced significantly greater decreases
      in summary symptom score (p = 0.005), itch (p = 0.005), tearing (p = 0.004),
      overall eye condition (p = 0.001), and clinician-evaluated conjunctival edema (p
      = 0.018), and significantly better (p = 0.001), and patient (p = 0.001) opinions
      of treatment effectiveness at the peak pollen period. Additionally, the
      superiority of nedocromil sodium compared to vehicle approached statistical
      significance in redness reduction (p = 0.087) and clinician-evaluated
      conjunctival injection (p = 0.087). There were no serious treatment-related
      adverse events in either treatment group. In summary, nedocromil sodium 2%
      ophthalmic solution b.i.d. was found to be effective and to have a favorable
      safety profile in the treatment of seasonal allergic conjunctivitis.

PMID- 10951892
TI  - Stress, immune regulation, and immunity: applications for asthma.
AB  - The neuroendocrine mediators reach the cells of the immune system either through
      the peripheral circulation or through direct innervation of lymphoid organs.
      Primary and secondary lymphoid organs are innervated by sympathetic nerve fibers.
      Lymphocytes and monocytes express receptors for several stress hormones,
      including CRH, ACTH, cortisol, norepinephrine, and epinephrine. Therefore, it is
      reasonable to conclude that the neuroendocrine hormones released during a
      stressful event could alter immune function and subsequently alter the course of
      immune-based diseases. The impact of psychological stress on immune function has
      been the subject of extensive research efforts. Using a variety of models from
      largely healthy humans undergoing various forms of natural and experimental
      stress models, stress has been associated with suppression of NK activity,
      mitogen- and antigen-induced lymphocyte proliferation and in vitro production of
      IL-2 and IFN-gamma. Psychological stress is also associated with a higher rate of
      in vivo hypoergy to common recall-delayed type hypersensitivity antigens. These
      studies have suggested that psychological stress suppresses various components of
      CMI responses. Also, data suggest that chronic stress does not simply suppress
      the immune system, but induces a shift in the type-1/type-2 cytokine balance
      toward a predominant type-2 cytokine response. Such a change would favor the
      inflammatory milieu characteristic of asthma and allergic diseases. Recent
      studies using well-controlled teenage asthmatic subjects demonstrated
      immunological changes (decreased NK cell cytotoxicity and cytokine alterations)
      in response to exam stress. These immune alterations are consistent with a
      cytokine milieu that could potentially worsen asthma. However, there were no
      changes in peak flow rates, self-report asthma symptoms, or medication use. The
      lack of correlation between stress and asthma symptoms may have been related to
      the timing of the visits in relation to the stressor, the duration of the
      stressor, disease severity, or a lack of accurate self-report data.
      Alternatively, stress-mediated exacerbations of asthma may require multiple
      alterations by stress, including cytokine dysregulation or vagal-mediated airway
      hyperresponsiveness. The rationale for stress management in asthma is based upon
      the notion that stress causes a change in immune balance that would favor asthma
      activity in susceptible individuals. This immune imbalance can be found in
      TH1/TH2 cytokine changes that occur with stress. Although it has not yet been
      demonstrated that stress can cause or directly influence the development of
      asthma, it is interesting to note that both the incidence and prevalence of
      asthma continue to increase and are higher in urban than in rural areas. Among
      other differences is the well-appreciated higher chronic stress levels associated
      with urban living.

PMID- 10951893
TI  - Asthma among the famous. Edith Wharton (1862-1937) American novelist.

PMID- 10951894
TI  - Masseter muscle activity during vestibular stimulation in man.
AB  - Experimental data report that vestibular afferents affect trigeminal system
      activity. The aim of this work was to evaluate whether static vestibular
      stimulation affects the excitability of trigeminal motoneurons in man. In order
      to assess this, voluntary EMG activity of masseter muscles as well as duration
      and latency of the early and late components of EMG exteroceptive silent period
      were evaluated while keeping the subject in vertical position and during 20
      degrees static tilt. The experiments were performed on ten adult subjects with no
      orofacial, neurologic and otologic disorders. Each subject sat on a chair, which
      kept the complex head-jaw-neck-trunk and the limbs securely fixed, in order to
      minimize any interference due to the activation of somatosensory and
      proprioceptive afferents from these districts. The subjects were instructed to
      contract masseter muscles at 25% of their maximum bite force and the isometric
      force monitoring was used as visual feedback. Exteroceptive silent period (ESP)
      of masseter EMG was elicited by electrically stimulating the inferior inter
      incisal gum. Results showed that static vestibular stimulation induced
      asymmetrical responses on voluntary masseter muscle activity, which was reduced
      to 70.3 +/- 16.1% (mean +/- S.D.) of the control value during ipsilateral tilt
      and increased to 128.8 +/- 13.0% during contralateral tilt. The duration of the
      early (ESP1) and late (ESP2) silent periods was also affected: during ipsilateral
      tilt ESP1 and ESP2 duration increased to 130.0 +/- 3.5% and to 122.1 +/- 2.1% of
      control, respectively; during contralateral tilt it was reduced to 76.8 +/- 1.2%
      and to 83.0 +/- 1.7% of control, respectively. On the contrary, changes in
      latencies were not significant. These data evidenced an asymmetrical effect
      exerted on trigeminal motor activity by static tilt. Since the influence of all
      receptors which could be activated by static tilt, except that arising from the
      macular ones, was minimized in this study, it is likely that the observed
      effects, induced by static tilt on masseter muscle activity, were of macular
      origin.

PMID- 10951895
TI  - Contribution of the cerebellar anterior vermis to the gain and spatiotemporal
      properties of the vestibulospinal reflex: a behavioural and cellular analysis.
AB  - Functional inactivation of the lobules IV-V of the cerebellar vermis obtained by
      local microinjection of the GABA-A agonist muscimol, depresses, in decerebrate
      cats, the amplitude of the VS reflex recorded from the forelimb extensor TB and
      may occasionally affect its spatial and/or temporal properties. The activity
      changes induced by tilting the animal head in all the possible directions were
      uniformely reduced. Experiments of unit recording from the same region submitted
      in other experiments to the drug injection, revealed that a large proportion of P
      cells (67%) showed spatially tuned responses to the labyrinth input,
      characterized by preferred directions which were uniformely scattered over the
      horizontal plane. Neurons with opposite orientations could be found within a
      relatively narrow volume of corticocerebellar tissue, that could have been easily
      inactivated by injected volumes (0.25 microliter, 8 micrograms/microliter) of
      muscimol. We proposed that the spatial tuning of the P-cell responses to the
      labyrinth input is a basic property which allows the cerebellum to control the
      gain of VS reflexes elicited by head tilts in a broad directional range.

PMID- 10951896
TI  - C-Fos expression in the basilar pontine nuclei and reticulotegmental nucleus of
      the rat following lateral cerebellar nucleus stimulation.
AB  - The present study was carried out with the aim to observe whether, in the rat,
      the electric activation of the projection form the cerebellar lateral nucleus
      (LN) to the basilar pontine nuclei (BPN) and to the reticulotegmental nucleus
      (RtTg) is capable to induce the c-Fos expression. In particular, we compared the
      effects of a continuous LN stimulation at low-frequency (tonic stimulation) with
      those induced by high frequency pulse trains (phasic stimulation). The observed
      results show that the stimulation of LN induces c-Fos expression in a significant
      fraction of neurons in the contralateral BPN and RtTg. It was also observed that
      phasic stimulation was slightly more capable in producing c-Fos expression with
      respect to the tonic stimulation. Furthermore, systemic injection of MK-801, a
      non-competitive antagonist of the NMDA receptor, reduced the LN-induced c-Fos
      expression in BPN and RtTg. In contrast, GYKI 52466, an AMPA/kainate receptor
      antagonist, did not change the LN driven induction of c-Fos in both BPN and RtTg.

PMID- 10951897
TI  - Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain
      and cerebellar structures of albino rats.
AB  - Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy
      (UL) modified the concentration of norepinephrine (NE) as well as of dopamine
      (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in
      different areas of the cerebral and the cerebellar cortex and the striatum. The
      results obtained in 38 rats submitted to UL were compared to those of 18 rats
      submitted to sham-operation. The animals were operated under sodium pentobarbital
      anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL
      showed phenomena of deficit (1.5-3 h after the lesion) followed by partial
      vestibular compensation (3-6 h after the lesion). Significant changes in the
      content of NE were neither found in different areas of the cerebral and the
      cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h
      after the lesion a bilateral increase in the NE content occurred in all the
      explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and
      occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as
      in the striatum. This increase, however, was more prominent in the parieto
      temporal areas of the neocortex of the intact side, in all the explored areas of
      the cerebellar cortex of that side, as well as in the striatum of the lesioned
      side. This asymmetric increase in NE content could not be attributed, at least
      exclusively, to a generalized activation of the noradrenergic LC nuclei of both
      sides, due to waking and/or stress which may occur after UL, but did rather
      depend on asymmetric changes in unit discharge of the vestibular nuclei
      projecting to the LC of both sides, following UL. In particular, the increased
      discharge of the vestibular nuclei of the intact side would lead to activation of
      noradrenergic neurons projecting particularly to the parieto-temporal cortex and
      the cerebellar cortex of the intact side, as well as to the striatum of the
      lesioned side. A bilateral increase in NE content was still observed in different
      areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This
      increase, however, was of smaller entity than that observed in the same areas 3 h
      after UL and quite symmetric. The content of DA and its metabolite DOPAC
      decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This
      effect was attributed to a reduced synthesis and release of DA, which probably
      resulted from a reduced facilitatory influence that the deafferented vestibular
      nuclei exert on the dopaminergic, nigrostriatal system of both sides, although
      mainly on the intact side. The corresponding values, however, bilaterally
      recovered to slightly increase with respect to the control values in rats
      sacrificed 3 and 6 h after UL. In these experiments the content of both DA and
      DOPAC remained symmetric on both sides after UL, in contrast with the bilateral
      but asymmetric increase in NE concentration observed in the same structure 3 h
      the lesion. The present results integrate and extend those of previous
      experiments showing that: 1) albino rats sacrificed 6 h after UL displayed an
      increased synthesis of NE, which affected particularly the LC of the intact side
      as well as the medial vestibular nuclei of both sides (21); and 2) the structures
      which showed an increased content of NE at given time intervals after UL also
      displayed an increase in the expression of the immediate early gene c-fos (cf. 16
      for ref.). These findings suggest that bilateral but asymmetric activation of the
      noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos
      expression in several target structures, thus contributing to the plastic changes
      responsible for vestibular compensation. In conclusion, it appears that UL
      induces in several brain structures of albino rats a short-term increase in
      synthesis and release of NE. (ABSTRACT TRUNCATED)

PMID- 10951898
TI  - Electromyographic and kinematic studies of tail movements during falling in cats.
AB  - When falling from an inverted position, EMG activities of tail muscles (the m.
      extensor caudae lateralis, m. abductor caudae externus, m. flexor caudae longus)
      and tail movements were recorded in 7 long-tailed adult cats. After being
      released from an elevated position, cat rotates the tail in a reverse direction
      to rotation of other parts of the cat's body then lands on four legs. Rotation of
      the tail was started by EMG activities of the tail muscles on one side. Both
      synchronized and alternating groups of discharge occur between its left and right
      side, while extensor and flexor movements and displacements of its tail appear in
      the air. After transection of ventral roots from the coccygeal spinal segments
      innervating tail muscles, cats often fail to land on four legs. These facts
      suggest that that tail movements control body balance in the air when falling
      from an inverted position.

PMID- 10951899
TI  - ["Apodictic medicine" and "empirical medicine": value of evidence based medicine
      in psychiatry].

PMID- 10951900
TI  - [Quantitative evaluation of sharing practices of materials at risk for infectious
      virus contamination by intravenous opiate users seeking treatment--application of
      the RAB(Risk for AIDS Behavior) self-administered questionnaire].
AB  - The objective of this study was to quantify the occurrence of AIDS risk related
      sharing activities in i.v. opiate users seeking treatment using a self
      administered questionnaire. Subjects were recruited among first time consultants
      of an outpatient clinic and assessed using the Risk for AIDS Behavior
      questionnaire (RAB), a self administered questionnaire that assesses both needle
      sharing and unprotected sexual activity; the Beck Depression Inventory (BDI) a
      self administered questionnaire that assesses depressive symptoms; and the
      Addiction Severity Index (ASI), a 45-min, structured interview that provides
      assessments of problem severity in seven functional areas commonly impaired among
      drug abusers. Among the 102 patients who came in for treatment, all 66 subjects
      reporting i.v. drug abuse agreed to participate. The study was based on the data
      collected from these 66 subjects of whom 49 were males (74%) and mean age +/- SD
      was 31 +/- 5. Fifty-eight-percent of theses subjects reported having shared
      needles or related paraphernalia over the past 6 months. Despite informational
      campaigns on the risks of sharing and despite the well spread knowledge of such a
      risk, most i.v. opiate users seeking treatment report having shared at least once
      over the previous 6 months.

PMID- 10951901
TI  - [Clinical dimensions and visually guided saccades in schizophrenia].
AB  - Eye movement anomalies are more frequent in schizophrenic patients than in
      healthy subjects. This study deals with visually guided saccadic eye movements in
      seventeen schizophrenic patients [ten untreated (neuroleptic-naive or free),
      seven treated patients] and their correlations between symptoms presented by
      patients and oculomotor performances. There was no significant difference between
      the patients and the control group in visually guided saccades tasks. However,
      negative correlations between oculomotor performance and positive or
      disorganisation symptomatology were found. Thus, although no major oculomotor
      dysfunction in response to external stimulus was seen in schizophrenic patients,
      some symptoms were linked to oculomotor performance impairment. Thus psychiatric
      symptoms might share some common cerebral circuits which those involved in
      oculomotor tasks.

PMID- 10951902
TI  - [Clinical and prognostic characteristics associated with addictive comorbidity in
      hospitalized psychiatric patients].
AB  - The aims of this study were to estimate: 1) the prevalence of substance use
      disorder, 2) the social and clinical characteristics associated to such a
      comorbid disorder in patients hospitalised in psychiatry. METHOD: Patients
      consecutively hospitalised for a non-addictive disorder were included in the
      present survey. A standardised method was used to collect information on clinical
      and social characteristics. DSM IV diagnoses, including those of substance use,
      were made using a structured diagnostic interview and all available clinical and
      historical informations collected during the hospital stay. RESULTS: We have
      included 127 patients fulfilling the diagnostic criteria for affective disorders
      (n = 61), non-affective psychotic disorder (schizophrenia, schizoaffective
      disorder, delusional disorder, other psychotic disorders, n = 50) and personality
      disorder (n = 16). Among these patients, 11.8% presented with a current
      abuse/dependence to alcohol (lifetime prevalence: 25.2%), 11% to cannabis
      (lifetime prevalence: 22.8%). The lifetime prevalence for any other substance
      disorder was 2.4%. The subjects presenting with an abuse/dependence to alcohol
      had a higher rate of psychiatric hospitalisation (OR = 2.9; 95% CI 1.0-8.1; p =
      0.04) and had more frequently a history of attempted suicide (OR = 2.6; 95% CI
      1.0-6.5; p = 0.04). The cannabis misuse was associated with medication
      noncompliance (OR = 3.1; 95% CI 1.1-9.1; p = 0.04) and more frequent penal
      problems (OR = 15.0; 95% CI 2.9-78.7; p = 0.001). CONCLUSION: Cannabis and
      alcohol misuse have a negative, but different, impact on social adaptation and
      clinical outcome in subjects with psychiatric disorder. These results confirm the
      necessity to systematically assess this type of comorbid disorder and to
      distinguish the different substances.

PMID- 10951903
TI  - [Validation of the French version of of the Telic Dominance Scale (TDS)].
AB  - There are connections between sensation seeking, difficulties to plan the future
      and to work towards aims, in relation with fails of mentalisation and addictions.
      Those characteristics have been described by M.J. Apter as a paratelic dominance
      of the person, in opposition with the telic dominance. That dimension of the
      personality has been formalizing as a part of the Reversal Theory. After a
      presentation of the foundations of this theory, and the validity's studies of the
      English version of the Telic Dominance Scale, the article explains the
      proceedings of validation of the TDS French version (Echelle de dominance
      telique). The population is 72 subjects: 38 addicts--ASI criteria--and 34
      control. The component analysis with varimax rotation doesn't allow to find the
      three factors of construction, but there is a good inter-correlation between the
      factors. Alpha's Cronbach coefficient is correct, underlining the intern
      consistency of the scale. At the comparison between groups, the scale has a good
      sensitivity. There is no correlation between the variables of population (age,
      sex, employment) and TDS. Lastly, there is a correct correlation between self
      esteem, anxiety, depression and TDS. The results make TDS a scale with an
      imperfect validity in its French version, but this scale has sufficient qualities
      to be used in the case of short studies about addicted population. In association
      with others instruments, this scale can assess a stable component of the
      personality giving a measure of the addictive risk.

PMID- 10951904
TI  - [Structured interview guide for evaluating depression in elderly patients,
      adapted from DSM IV and the GDS, HDRS and MADRS scales].
AB  - Depression in the elderly looks like depression in adulthood, without mention of
      a strict clinical specificity. In fact, depression in the elderly presents a
      semiologic inflexion, and a symptomatology attenuation. Some signs could be
      considered by others to twists as belonging the normal aging, but are in reality
      clinical elements of depression symptomatology. These reasons, as well as the
      variability of evaluation methods used, make that this pathology remains often
      underdiagnosed. Nevertheless, epidemiological studies have pointed out that this
      trouble is relatively frequent. Depression in the elderly is important to be
      detected, in reason that it could be treated, allowing to prevent somatic
      complications, repetition of troubles, relapse, suicide solution, and dementia
      development. Most of authors considers that the most useful diagnostic tests are
      screening assessments. In the geriatric population, about 43 tools exists for the
      depression, but some of these are better than other. Three validated rating
      scales are specially interessant for the depression in the elderly: GDS of
      Yesavage (Geriatric Depression Scale), HDRS of Hamilton (Hamilton Depression
      Rating Scale) and MADRS of Montgomery and Asberg (Montgomery and Asberg
      Depression Rating Scale). The purpose of this work is to present a psychiatric
      interview guide, allowing to better specify depressive symptoms with old
      subjects, constructed and adapted from these 3 rating scales and the DSM IV
      criteria. In order that, we have first synthetized all of the items of the 3
      scales. Then, by following diagnostic criteria of the DSM IV, we have constructed
      with uniform manner the interview guide. It has been built to evaluate general
      clinical aspects, but also to precise clinical points. The interviewer can ask
      question, take into account the clinical dimension, and appreciate the intensity
      of the trouble. The guide has been experimented and tested with older depressive
      subjects. After a necessary training phase to control the assessment system, the
      guide is usable during a clinical interview. It allows to collect, in a
      standardized manner, sufficiently data to establish the diagnosis and to quantify
      the intensity of the trouble. Conceived initially for a practical clinic use,
      this guide will have future use in research studies, in return for some ulterior
      validation works.

PMID- 10951905
TI  - [Narcissistic crisis and prediction of post-partum depression: validation of a
      self-report questionnaire].
AB  - We sought a relationship between disorders of the narcissistic transition during
      pregnancy and post-partum depression. We designed a self-report questionnaire
      VASANT (Visual Analogic Scale for Assessment of Narcissistic Transition) in an
      attempt to identify women at risk from post-partum depression. A preliminary
      validation was carried out on 52 pregnant women. Seventeen women (33%) were
      identified using a semi-directive interview as suffering from a disorder in the
      narcissistic transition. These women had a significantly higher VASANT score
      (67.7 +/- 14.2 versus 20.2 +/- 8.4) than the others and had a higher incidence of
      post-partum depression. The value of the VASANT scale for prediction of post
      partum depression is discussed.

PMID- 10951906
TI  - [Selective serotonin reuptake inhibitors and depression in the child and
      adolescent].
AB  - Child and adolescent depression is a serious psychiatric disorder with a
      considerable impact on psychosocial functioning, and an associated risk of
      mortality due to suicide. The potential interest of selective serotonin reuptake
      inhibitors (SSRI) for child and adolescent depression treatment is now well
      recognized. Since a recent date, this class of antidepressants is recommended as
      first-line medication (18, 24). Open studies have shown a response rate to SSRI
      from 60% to 75% and their efficiency was demonstrated through a controlled trial
      of high methodological quality, conducted by Emslie et al. in 1997 (10). The side
      effects of SSRI are generally mild and seldom require to discontinue the
      treatment. Research on this domain is tending toward increasing data on the
      efficacy, safety and pharmacokinetics of SSRI on children and adolescents. The
      different SSRI specificities and the potentialisation of these compounds by a
      molecule of the same class, or by other medications (lithium, buspirone,
      triodothyronine), are currently studied. It seems useful to us to do a review of
      this category of antidepressants, even though data are incomplete; it has not
      gone through AMM approval in children below the age of 15, but it appears to be
      efficient and promising.

PMID- 10951907
TI  - [Alexithymia, health and psychopathology].
AB  - The term "alexithymia" is derived from the Greek and means "no words for
      feeling". Coined by Sifneos in 1972, alexithymia refers to a relative narrowing
      in emotional functioning. The salient clinical features of alexithymia include
      difficulties in recognizing and verbalizing feelings, endless description of
      physical symptoms instead of emotions, concrete speech and thought closely tied
      to external events, paucity of fantasy life. Although initially described in the
      context of psychosomatic illness, alexithymic characteristics may be observed in
      patients with a wide range of medical and psychiatric disorders. This study
      purpose to investigate the relationship between alexithymia and concepts of
      health's psychology: locus of control, family's cohesion and adaptability,
      personality's concepts,... Three groups of patients were established on base of
      their diagnosis: depression (n = 16), alcoholism (n = 16) and control group (n =
      16). The following measures were administered: family's cohesion and adaptability
      (Olson), Multidimensional Health Locus of Control (Wallston and Wallston),
      externality scale (Rotter), Minnesota Multiphasic Personality Inventory. The
      results show alexithymic personality is less internal (t = 2.72; p = 0.011) than
      non-alexithymic subject (m = 20.88 +/- 6.19 vs m = 26.06 +/- 4.52). Furthermore
      the family's cohesion is lower (t = 2.961; p = 0.008) for the alexithymics than
      the non-alexithymics (m = 30.46 +/- 10.38 vs m = 40.27 +/- 5.44). This
      conclusions added to the more pathological personality's profile (11 scales on 14
      were significant higher for for alexithymics) of alexithymics at the MMPI
      indicate alexithymia's concept is central in psychopathology if measures used are
      issued by the health's psychology.

PMID- 10951908
TI  - [Initiation of treatment with olanzapine in a patient hospitalized at UMD].
AB  - Miss R is a 28-year-old patient presenting with paranoid schizophrenia. During a
      second acute psychotic episode involving attempted murder of her son, she was
      forcibly hospitalized in a Difficult Patients Unit. Following failure of
      treatment with a standard antipsychotic, therapy with olanzapine was rapidly
      initiated. Symptomatic improvement occurred quite rapidly, and the patient re
      entered into contact with others and was once again able to relate normally with
      her son. By means of an admittedly heavy management regimen, this patient,
      considered as dangerous, was able to follow a programme resulting in independence
      and renewed social integration. After two years of follow-up, improvement
      persisted and the patient now lives alone in an apartment. Analysis of this
      "exemplary" case and of current data in the literature suggests that more
      extensive use of new antipsychotics may be envisaged in the management of acute
      psychotic episodes.

PMID- 10951909
TI  - [Biological therapies of behavioral and psychological symptoms of dementia:
      update and prospects].
AB  - In addition to cognitive deficits, dementia is characterized by noncognitive
      behavioral disorders that are highly prevalent as the disease progresses into its
      later stages. These "behavioral and psychological signs and symptoms of dementia"
      are probably more important on a day to day basis than the cognitive deficits: in
      some patients, they are not a source of major disability but rather just a
      nuisance and may not require active pharmacological treatment; in others, they
      can be source of substantial anxiety and distress. Among the many behavioral
      symptoms of dementia, the group of behaviors included under the label of
      depression, anxiety, agitation, aggressiveness or uncooperativeness are the most
      burdensome and frequently lead to the prescription of an antipsychotic drug. They
      often precipitate institutional placement. The rationale for the use of
      psychotropic drugs is partially based upon phenomenological similarities of some
      behaviors observed in elderly demented patients to signs and symptoms of
      psychiatric disorders such as depressive illnesses, anxiety or psychotic
      disorders in non-elderly patients. In fact, the "psychiatric symptoms" in
      Alzheimer's disease or other dementia are often qualitatively different from
      those that characterize depressive, anxious or psychotic disorders. Many
      monoaminergic acquired deficits in dementia may also explain why treatment
      outcome studies suggest that the psychotropic drugs are less effective in
      patients with Alzheimer's disease or frontal lobe dementia than in patients with
      psychiatric disorders. The role of cholinesterase inhibitors in the treatment of
      neuropsychiatric symptoms in Alzheimer's disease may represent a novel and
      promising therapeutical approach.

PMID- 10951910
TI  - [Update on "expressed emotions"].
AB  - The present article is meant to sum up the current state of scientific knowledge
      with regard to the concept of "Emotional Expression" and its very implementation
      in the clinical and therapeutical field which are well-known in anglo-saxon
      countries but very little applied and known in France. "Emotional Expression"
      (EE), which came out of research and studies undertaken by Brown (1959) and later
      on, Vaughn and Leff (1976), defines interaction between a schizophrenic patient
      and his close environment according to 3 criterium: judgmental comments and
      criticism, hostility, emotional over-involvement. Family surroundings are
      characterized by strong EE or weak EE according to the frequency and the quantity
      of the measures during a typical standard family-interview: the Camberwell Family
      Interview (CFI). A strong EE is considered as being a non-specific factor.
      "Emotional Expression" proves to be a predictable indication for relapse in terms
      of psychiatric affluence (positive symptoms), hospitalization rate and psycho
      social adjustment process. The possibilities of forecasting do not concern
      specifically schizophrenia as the relation between family climate and relapse can
      be observed in other mental pathology as well. The psycho-educational approach
      which is induced by this research trend is based on a concept of a partnership
      between the patients's family and the patient. The purpose in fact is to bring
      about changes within the relationship of the patient and his environment so as to
      reduce judgmental criticism, hostility and emotional over-involvement
      (information programs concerning etiology, therapeutical strategies in view of
      improving understanding of the illness and to reorganize proper family
      relationship). The advantage of such a concept which is well-known lies in the
      fact that it helps to find out those family surroundings with strong EE who
      represent factors of relapse for psychiatric patients and to suggest therefore
      therapeutical treatment, the purpose of which should be defined together with all
      those concerned namely, the patient, the family, the therapeutist so as to
      intervene during the evolution of the illness. The literary bibliographical
      review which we have made lead us to find the existence of a wide field of
      research with results showing clearly the predictable aspects of EE in the
      illness process. In this way, new approaches in the "intake" of schizophrenic
      patients and their families are clearly defined.

PMID- 10951911
TI  - [Acute nuptial psychosis: apropos of 16 cases].
AB  - The marriage, an over-invested social event in our Maghrebin cultural context,
      can, in certain cases, generate major psychiatric disorders especially of
      psychotic types. The aim of our study is to describe the clinical specifications
      of these psychotic disorders and to discuss the surroundings and individuals
      factors incriminated in their genesis. Our retrospective study concerns sixteen
      patients suffering from acute psychotic disorders precipitated by marriage. Male
      subjects represented 75% of cases with an average age of 26.8 years. 62.5% of
      them have no psychiatric background. The disorders first appeared after the
      marriage in 75% of cases, often during the first week. 68% of cases have
      delirious syndrome. Schizophreniform and brief psychotic disorders were often
      reported. The importance of the cultural factors was particularly prominent in
      the starting of these disorders.

PMID- 10951912
TI  - [Risperidone and edema: apropos of a case].

PMID- 10951913
TI  - [Information for the psychiatric patient].

PMID- 10951914
TI  - Acts and omissions revisited.

PMID- 10951915
TI  - POM + EBM = CPD?

PMID- 10951917
TI  - Causal authorship and the equality principle: a defence of the acts/omissions
      distinction in euthanasia.
AB  - This paper defends the acts/omissions distinction which underpins the present law
      on euthanasia, from various criticisms (including from within the judiciary
      itself), and aims to show that it is supported by fundamental principles. After
      rejecting arguments that deny the coherence and/or legal relevance of the
      distinction, the discussion proceeds to focus on the causal relationship between
      the doctor and the patient's death in each case. Although previous analyses,
      challenging the causal efficacy of omissions generally, are shown to be
      deficient, it is argued that in certain cases of causing death by omission the
      causal authorship of the doctor lapses. The final part of the paper examines why
      this should be morally significant and proposes an answer in terms of the
      principle of equality. Assuming all other factors are equal, the infringement of
      this principle provides an additional reason against actively killing a patient,
      which is not present in cases of passively letting die.

PMID- 10951916
TI  - Starting clinical trials of xenotransplantation--reflections on the ethics of the
      early phase.
AB  - What kind of patients may be recruited to early clinical trials of
      xenotransplantation? This is discussed under the assumption that the risk of
      viral infection to the public is non-negligible. Furthermore, the conditions
      imposed by the Helsinki declaration are analysed. The conclusion is that only
      patients at risk of dying and with no alternative treatment available should be
      recruited to xenotransplantation trials in the early phase. For some of the less
      dangerous cell or islet cell xenotransplantation other categories might be
      recruited. The risk of cell and islet cell xenotransplantation should, however,
      be weighted against the development of other technologies. In order to safeguard
      the public, the opt-out clause in the Helsinki declaration should not be fully
      applied. Legally binding rules on obligatory monitoring and restrictions should
      be imposed--before clinical trials start.

PMID- 10951918
TI  - Avoiding anomalous newborns: preemptive abortion, treatment thresholds and the
      case of baby Messenger.
AB  - In its American context the case of baby Messenger, a preterm infant disconnected
      from life-support by his father and allowed to die has generated debate about
      neonatal treatment protocols. Limited by the legal and ethical norms of the
      United States, this case did not consider treatment protocols that might be
      available in other countries such as Denmark and Israel: threshold protocols
      whereby certain classes of newborns are not treated, and preemptive abortion
      allowing one to choose late-term abortion rather than risk delivery. Each offers
      a viable and ethically sound avenue for dealing with the economic and social
      expense of anomalous newborns by aborting or not treating those most likely to
      burden the health care system. Objections that these protocols are antithetical
      to American bioethical principles are considered but rejected as each policy
      answers to economic justice, utility and respect for autonomy.

PMID- 10951919
TI  - Presumed consent in emergency neonatal research.
AB  - Current methods of obtaining consent for emergency neonatal research are flawed.
      They risk aggravating the distress of parents of preterm and other sick neonates.
      This distress, and the inevitable time constraints, compromise understanding and
      voluntariness, essential components of adequately informed consent. Current
      practice may be unjust in over-representing babies of more vulnerable and
      deprived parents. The research findings may thus not be generalisable. Informing
      parents antenatally about the possible need for emergency neonatal research, with
      presumed consent and scope for opting out, would address these problems. It would
      spare parents of sick neonates, already terrified by their baby's illness,
      further distress. Experience with opting out suggests that recruitment might
      increase, thus generating earlier results, without compromising parental
      understanding of the nature and purpose of the research.

PMID- 10951921
TI  - Genetics services in a social, ethical and policy context: a collaboration
      between consumers and providers.
AB  - We report a unique, collaborative effort by users and providers of genetic
      services to arrive at outlines for optimal ethics and clinical practice. Using
      focus groups of consumers (users) and providers (held separately), a provider
      consumer project team developed 1) a consumer wish list, 2) an experientially
      based ethical overview of situations arising in practice, and 3) detailed
      suggestions for consumer-provider interactions in clinical settings. Consumers
      were primarily interested in accurate information, respect for persons, a
      smoothly functioning team, with the consumer as an equal member of the team,
      family integrity, and providers who knew the limits of their knowledge and were
      willing to refer. "Non-directive" counselling and privacy were not major issues
      in consumer focus groups; some thought providers should openly state their own
      opinions. Providers had a rather different list of priorities. Books and papers
      on clinical ethics usually originate from bioethicists and physicians. This pilot
      project is unique in including consumers and providers equally.

PMID- 10951923
TI  - Choices without reasons: citizens' juries and policy evaluation.
AB  - Citizens' juries are commended as a new technique for democratising health
      service reviews. Their usefulness is said to derive from a reliance on citizens'
      rational deliberation rather than on the immediate preferences of the consumer.
      The author questions the assertion of critical detachment and asks whether juries
      do in fact employ reason as a means of resolving fundamental disagreements about
      service provision. He shows that juries promote not so much a critically detached
      point of view as a particular evaluative framework suited to the bureaucratic
      idiom of social welfare maximisation. Reports of jury practice reveal a tendency
      among juries to suppress by non-rational means the everyday moral language of
      health care evaluation and substitute for it a system of thought in which it can
      be deemed permissible to deny treatment to sick people. The author concludes that
      juries are chiefly concerned with non-rational persuasion and because of this
      they are morally and democratically irrelevant. Juries are no substitute for
      voting when it comes to protecting the public from zealous minorities.

PMID- 10951922
TI  - Ethical-legal problems of DNA databases in criminal investigation.
AB  - Advances in DNA technology and the discovery of DNA polymorphisms have permitted
      the creation of DNA databases of individuals for the purpose of criminal
      investigation. Many ethical and legal problems arise in the preparation of a DNA
      database, and these problems are especially important when one analyses the legal
      regulations on the subject. In this paper three main groups of possibilities,
      three systems, are analysed in relation to databases. The first system is based
      on a general analysis of the population; the second one is based on the taking of
      samples for a particular list of crimes, and a third is based only on the
      specific analysis of each case. The advantages and disadvantages of each system
      are compared and controversial issues are then examined. We found the second
      system to be the best choice for Spain and other European countries with a
      similar tradition when we weighed the rights of an individual against the
      public's interest in the prosecution of a crime.

PMID- 10951920
TI  - Are medical ethicists out of touch? Practitioner attitudes in the US and UK
      towards decisions at the end of life.
AB  - OBJECTIVES: To assess whether UK and US health care professionals share the views
      of medical ethicists about medical futility, withdrawing/withholding treatment,
      ordinary/extraordinary interventions, and the doctrine of double effect. DESIGN,
      SUBJECTS AND SETTING: A 138-item attitudinal questionnaire completed by 469 UK
      nurses studying the Open University course on "Death and Dying" was compared with
      a similar questionnaire administered to 759 US nurses and 687 US doctors taking
      the Hastings Center course on "Decisions near the End of Life". RESULTS:
      Practitioners accept the relevance of concepts widely disparaged by bioethicists:
      double effect, medical futility, and the distinctions between heroic/ordinary
      interventions and withholding/withdrawing treatment. Within the UK nurses' group
      a "rationalist" axis of respondents who describe themselves as having "no
      religion" are closer to the bioethics consensus on withholding and withdrawing
      treatment. CONCLUSIONS: Professionals' beliefs differ substantially from the
      recommendations of their professional bodies and from majority opinion in
      bioethics. Bioethicists should be cautious about assuming that their opinions
      will be readily accepted by practitioners.

PMID- 10951925
TI  - Commercial predictive testing: the desirability of one overseeing body.
AB  - In Europe a process of harmonisation of standards and regulations on genetic
      testing has started. Public discussion and consultation are recommended, but it
      is not clear in every European country how the decision making process as regards
      the further introduction of genetic testing services should be formed. In this
      paper the usefulness and importance of an overseeing body for genetic screening
      and testing is founded on four lines of reasoning: (1) analysis of the role of
      value judgments in the use of the concept of (genetic) abnormality; (2) a
      balancing of potential benefits for all parties involved; (3) a balancing of
      potential disadvantages, and (4) the greater availability of commercial genetic
      tests in the future. It is further argued that such an overseeing body has
      advantages for all the interested parties.

PMID- 10951924
TI  - Neither consenting nor protesting: an ethical analysis of a man with autism.
AB  - This article critically examines the 25 June 1998 decision by the House of Lords
      regarding the psychiatric admission of a man with autism. Mr L was able neither
      to consent to, nor refuse, that admission and the disposition of his case
      illuminates the current debate regarding best interests of vulnerable adults by
      the judiciary and the psychiatric profession. This article begins with the
      assumption that hospitalisation was not the optimum response to Mr L's condition,
      provides alternative approaches to the interpretation of best interest and
      examines principles of liberty, anti-discrimination, and equal protection.

PMID- 10951926
TI  - Ethics briefings.

PMID- 10951927
TI  - Medicolegal certificates in investigations of asylum applications.

PMID- 10951928
TI  - [Preservation of vascular and cardiac capital in the patient with chronic kidney
      failure].
AB  - Preservation of the vascular and cardiac capital is an essential objective at all
      times in patients with chronic renal failure, even before end-stage renal
      failure, at which time the urologist may need to perform surgical procedures on
      the urinary tract in the presence of uropathy. Medical and paramedical teams must
      be aware of the importance of preservation of the capital venous of the upper
      extremity and the risks of subclavian catheterization at this stage. When
      creating a vascular access, distal anastomoses should be preferred, sometimes at
      the cost of grafting, in order to preserve left ventricular function. Close
      collaboration with radiologists is now essential to manage complications of
      vascular accesses. The management of arteriovenous fistula after transplantation
      depends on many sometimes contradictory parameters and should be determined case
      by case. The importance of "economic" management of the patient's vascular and
      cardiac capital justifies global management of chronic renal failure by
      urologists perfectly familiar with the specific problems of these patients and
      trained to intervene throughout the course of the disease.

PMID- 10951929
TI  - [Treatments with alpha-stimulants in urology].
AB  - Neuropharmacology is a rapidly expanding field due to the regular discovery of
      new neurotransmitters or neuroreceptors. Hopes have now been raised for the
      treatment of vesicosphincteric disorders by developing molecules with a potential
      selective clinical action on the detrusor or the urethra. After a brief review of
      the neuroanatomy and general neuropharmacology of the sympathetic nervous system,
      the current indications for alpha agonists are reviewed and discussed. These
      indications include the treatment of priapism, retrograde ejaculation, and
      incontinence due to sphincter incompetence. The more recent use of agents with a
      central mechanism of action is also discussed (detrusor hyperactivity of spinal
      cord injury patients). The authors review the current indications and note that,
      although the use of these drugs is very specific and limited in the field of
      urology, it is nevertheless based on an interesting concept. Like molecules at
      the stage of clinical trials for peripheral or central targets, the mechanism of
      action of these molecules on the sympathetic adrenergic system needs to be more
      fully elucidated. Their adverse effects remain the limiting factor for use on
      peripheral targets.

PMID- 10951931
TI  - [Which urologic treatment alternatives are there for the hemophiliac patient?].
AB  - OBJECTIVE: Urological procedures are hazardous for hemophilic patients. The aim
      of this work is to report the treatment of 22 hemophilic patients in order to
      define prognosis factors and treatment options. MATERIAL AND METHODS: 22 patients
      have been treated: 8 had severe hemophilia, 5 A (FVIII < 1%), 3 B (F IX < 1%), 2
      had moderate hemophilia A (FVIII 2 to 6%) and 10 minor hemophilia A (F VIII 7 to
      30%). Two had acquired hemophilia with auto-anti-FVIII antibodies (ab). Four
      patients were HIV+. Eighteen patients were first referred to our hospital, and 3
      were transferred from an other institution for persistent hematuria: one with
      anuria, one after bladder neck incision, and the other following suprapubic
      prostatectomy. RESULTS: For patients without FVIII ab, a sufficient level of
      FVIII or IX (> 60%), could be achieved pre-operatively and maintained post
      operatively (4 to 20 days, according to the surgical procedure) by injections of
      FVIII, FIX or by injections of desmopressin. For one haemophilia A patient with
      anti-F VIII ab, transferred for uncontrollable bleeding after bladder neck
      incision, selective arterial embolization was successful. But for 2 patients with
      acquired haemophilia, improvement of the coagulation was insufficient, with human
      or porcine FVIII, activated prothombic complex concentrates or recombinant
      activated FVII. In spite of surgical procedures and arterial embolizations the 2
      patients died. CONCLUSION: The urological treatment of haemophilic patients needs
      to be performed in specialised centers. For patients without FVIII ab, classical
      urological procedures can be performed. But for patients with FVIII ab when
      alternative treatments (radiotherapy, LHRH agonists) can be used, the surgical
      procedures must be delayed; in emergency if hemostasis cannot be achieved
      arterial embolization could be useful.

PMID- 10951930
TI  - [Laparoscopic lumbo-aortic lymphadenectomy in early-stage non-seminomatous germ
      cell tumors of the testis: Why? How?].
AB  - OBJECTIVES: Laparoscopic lumbo-aortic lymphadenectomy is proposed in order to
      decrease the morbidity of pretreatment lymph node dissections for early stage
      NSGCT of the testis. Two approaches are presented and compared retrospectively:
      the transperitoneal approach and the extraperitoneal approach. MATERIAL AND
      METHODS: From 1991 to 1999, 57 patients with clinical stage I (50) to IIA (7)
      NSGCT underwent pretreatment laparoscopic investigation of the para-aortic lymph
      nodes: 32 transumbilical transperitoneal dissections and 25 internal iliac
      extraperitoneal dissections were performed. RESULTS: Only the 19 patients with
      lymph node invasion received chemotherapy. All serious complications occurred in
      the transperitoneal group: 1 case of chylous ascites and 2 cases of transient
      neurological complications, 2 cases of permanent ejaculation failure and 2
      extranodal recurrences among the 38 pN0 patients. CONCLUSIONS: Laparoscopy,
      especially extraperitoneal, appears to be a safe, effective and appropriate
      modality for pretreatment lumbo-aortic lymph node evaluation in early stage NSGCT
      of the testis.

PMID- 10951932
TI  - [Piezoelectric ESWL for ureteral calculi. Impact of topography and lithiasis
      measurements on therapeutic approaches and performance].
AB  - OBJECTIVE: To evaluate the influence of the site and dimensions of ureteric
      stones on the modalities and performances of in situ piezoelectric extracorporeal
      shockwave lithotripsy (ESWL). MATERIAL AND METHODS: A population of 385 patients
      with solitary radiopaque ureteric stones was analysed. The long axis of these
      stones (211 (55%) lumbar, 38 (10%) iliac and 136 (35%) pelvic stones) ranged from
      5 to 21 mm (mean = 8.2 mm). The initial shock wave frequency was 4/s. Lumbar
      stones were treated in the dorsal supine position under diaz-analgesia and pelvic
      stones were treated in the ventral supine position without systematic sedation.
      The influence of wave frequency (1 versus 4/s) on the level of sedation and
      therapeutic performances was studied on 146 patients with lumbar (n = 92) or
      pelvic stones (n = 54). The results were evaluated after only one ESWL session
      and were analysed statistically by Student's test and Fisher test. RESULTS: The
      overall complete success rate was 74%. Iliac stones were characterized by
      significantly (p < 0.05) lower (61%) performances. The results were inversely
      proportional to the size of the stones, as the complete success rate was only 25%
      for stones > 12 mm. For lumbar stones, a lower frequency allowed a very
      significant reduction (p < 0.0001) of the level of sedation required without
      affecting the performance. For pelvic stones, a low frequency significantly (p <
      0.05) limited the efficacy of ESWL, especially for stones > 8 mm (27% of complete
      successes). CONCLUSION: In situ piezoelectric ESWL allows effective management of
      most ureteric stones with of long axis between 5 and 10 mm. In the context of
      outpatient treatment, however, this approach requires modulation of the shock
      wave frequency according to the site of the stone. Another therapeutic approach,
      particularly endoscopy, should be considered for very large stones.

PMID- 10951933
TI  - [Analysis of urinary calculi in adults from the Moroccan Medium Atlas by Fourier
      transform infrared spectrophotometry].
AB  - OBJECTIVE: To determine the stone composition in adult patients from the medium
      Atlas of Morocco. MATERIAL AND METHODS: A series of 183 calculi from adult
      patients (males: 123, females: 60) collected in medium Atlas of Morocco was
      analysed by Fourier Transform infrared spectroscopy. The stones were surgically
      removed (n = 168) or spontaneously passed (n = 15). RESULTS: Kidney stones are
      encountered in 70.5% of calculi. The stones were twice frequent in males than in
      females (M/F = 2.10). Whewellite was the main component in 51.4% of the stones
      and 49.7% of the stone core, weddellite in only 7.1% of stones and 6.4% of the
      nuclei. Uric acid was predominant in 18% of stones and also 19.7% of nuclei, and
      carbapatite in 12.6% of stones and nuclei. All in all, whewellite was present in
      77.6% of calculi and weddellite in 25.1%, carbapatite in 68.3% and PACC in 23.5%,
      struvite in 15.3%, uric acid in 20.8% and ammonium hydrogen urate in 14.2% of
      cases. Struvite stones were more frequent in females and uric acid calculi in
      males, in particular in patients aged more than 60 years old. CONCLUSION: As
      observed in most countries, calcium oxalate was the most frequent major component
      of the stones (58.5%). Uric acid stones were more frequent (18%) than reported in
      Western countries, thus suggesting that particular dietary habits are involved in
      stone formation. The relatively high occurrence of struvite stones (8%) could be
      a marker of an insufficient early detection and treatment of chronic urinary
      tract infection.

PMID- 10951934
TI  - [Ureteral replacement with non-modelled isoperistaltic ileoplasty].
AB  - OBJECTIVES: To study the long-term morbidity and efficacy of ureteroileoplasty in
      a retrospective series of 18 patients. MATERIALS AND METHODS: 12 men and 6 women
      with a mean age of 50 years underwent ureteroileoplasty with unilateral
      replacement in 15 patients and bilateral replacement in 3 patients. A total of 21
      units renoureteral units were repaired by this technique. The pelvic ureter was
      replaced in 16 renoureteral units, the lumbar ureter was replaced in 1 case and
      the entire ureter was replaced in 4 cases. The commonest ureteral lesions were
      strictures secondary to ureteroscopy or ureterolithotomy (40%). All patients had
      normal renal function, except for one patient with serum creatinine of 224
      mumol/l. RESULTS: With a mean follow-up of 25 months (range: 3 to 64 months) all
      ureteroileoplasties were patent with no major morbidity. Only the patient with
      preoperative renal failure developed hyperchloraemic acidosis with deterioration
      of her renal function. CONCLUSION: In the absence of renal failure,
      ureteroileoplasty is an operation with low morbidity achieving good medium-term
      results.

PMID- 10951935
TI  - [Treatment of psoas abscess: percutaneous drainage or open surgery].
AB  - OBJECTIVE: Psoas abscess is currently an uncommon disease and is often difficult
      to diagnose because of its minor initial symptoms. We compare treatment by
      percutaneous drainage and surgery. MATERIAL AND METHODS: Five patients, all
      immunodepressed, which appears to be an important factor in the aetiology and
      pathogenesis of psoas abscess. Computed tomography appears to be the best
      diagnostic method. RESULTS: Three subjects underwent open surgery and developed
      serious complications in contrast with two patients treated by CT-guided
      percutaneous drainage, preceded by antibiotics. CONCLUSION: First-line
      percutaneous drainage appears to be the best approach at the present time,
      reserving open surgery for very large abscesses.

PMID- 10951936
TI  - [Retrovesical and retroperitoneal extrarenal hydatid cyst: descriptive study of 9
      cases].
AB  - OBJECTIVE: To determine the clinical, radiological and surgical features of
      retrovesical, retroperitoneal hydatid cyst and to discuss the aetiology and
      pathogenesis. MATERIAL AND METHODS: Nine cases of hydatid cyst operated in the
      urology department of Charles Nicolle hospital in Tunis between 1982 and 1998
      were reviewed: five retroperitoneal sites and 4 retrovesical sites. RESULTS:
      Retrovesical and retroperitoneal sites represent about 10% of all operations for
      hydatid cyst in our department. The mean age of our patients was 49.8 years. The
      clinical presentation was dominated by voiding disorders in the cases of
      retrovesical hydatid cyst (4 cases) and the appearance of a lumbar or abdominal
      mass with or without associated abdominal pain in the cases of retroperitoneal
      hydatid cyst (5 cases). The positive diagnosis was based on abdominopelvic
      ultrasonography, completed by computed tomography in 3 patients. All patients
      were treated by wide cyst resection with a favourable course and no recurrence.
      CONCLUSION: Retrovesical and retroperitoneal hydatid cysts are rare, but not
      exceptional in a country with a high endemic rate, such as Tunisia. The diagnosis
      can be confirmed by radiological investigations. Implantation of the hydatid
      larva is essentially haematogenous. However, secondary implantation in the pouch
      of Douglas of protoscolex derived from rupture of an intraperitoneal cyst can
      also be responsible for some retrovesical sites.

PMID- 10951937
TI  - [Modelled analysis of the effect of cystocele reduction with vaginal pack on
      miction in women with grade IV cystocele].
AB  - OBJECTIVES: To evaluate the effect of reduction of a cystocele by vaginal pack on
      the voiding of women with grade IV cystocele. METHODS: Two successive pressure
      flow analyses were performed in a series of 21 patients: the first after
      insertion of a vaginal pack to reduce the cystocele, and the second after removal
      of the pack. The VBN method was applied to analyse uroflowmetries, allowing
      evaluation of two parameters for each uroflowmetry: one reflecting the urethra
      and the other reflecting the detrusor. RESULTS: Only 14 patients were able to
      perform the 2 uroflowmetries in a single stream with a volume greater than 100
      ml. The vaginal pack improved the urethral parameter in 10 patients, but had no
      effect in the other 4 patients; it did not alter detrusor function. The urethral
      parameter was improved in patients whose obstruction was relieved according to
      the urodynamic criterion. CONCLUSIONS: Modelized analysis of pressure-flow
      analyses with and without a vaginal pack supports the conclusions of urodynamic
      tests concerning the preoperative status of patients with high grade cystocele by
      identifying those patients in whom the cystocele affects bladder emptying.

PMID- 10951938
TI  - [Are there any advantages in immediate assisted fertilization compared with
      differed fertilization?].
AB  - OBJECTIVES: To demonstrate a difference between the two assisted fertilization
      procedures. Can either of these procedures be preferred on the basis of
      preoperative parameters or criteria? A protocol was created to facilitate the
      patient's decision, as the results of IAF are better that those of DAF. METHODS:
      We have performed 39 in vitro fertilizations after testicular or epididymal sperm
      extraction since December 1995. We performed deferred assisted fertilization
      (DAF) in 19 patients with normal hormone assessment and normal testicular volume
      or after vasectomy and immediate assisted fertilization (IAF) for 20 patients
      with an abnormal assessment. RESULTS: The two groups, IAF and DAF, were
      homogeneous and did not present any differences in terms of age, aetiology of
      sterility, risk factors or preoperative hormonal parameters. Direct examination
      of sperm samples, the site of sampling and histological examination did not
      demonstrate any significant difference between the two groups. ICSI
      (IntraCytoplasmic Sperm Injection) was performed for 16 couples by IAF and for 14
      couples by DAF. We obtained 6 pregnancies (37.5%) in the IAF group and 2
      pregnancies (14.3%) in the DAF group. The two groups were identical in terms of
      the number of oocytes taken and embryos transferred. CONCLUSION: No significant
      difference was observed between the immediate and deferred fertilization
      techniques in terms of predictive factors, histology and quality of the direct
      examination, but the pregnancy rate was higher for IAF. We therefore think that
      this method should be preferred as the first-line procedure.

PMID- 10951939
TI  - [Acute appendicitis in kidney transplantation: value of laparoscopy].
AB  - Right iliac fossa pain in renal transplant recipients can raise diagnostic and
      therapeutic problems. The authors present two cases of acute appendicitis in
      renal transplant recipients treated by laparoscopy.

PMID- 10951940
TI  - [Retroperitoneal liposarcoma. Report of 3 cases].
AB  - We report three cases of retroperitoneal liposarcoma. Two patients required
      multiple surgical excisions for locoregional relapse diagnosed by surveillance
      based on CT-scan. One patient had radiotherapy. With the literature review we
      discuss the pathologic and therapeutic aspects of these lesions.

PMID- 10951942
TI  - [Prolapse of neovagina after anterior pelvic exenteration for urethral cancer].
AB  - The authors report the case of a patient undergoing anterior pelvic exenteration
      for cancer of the urethra with sigmoid colon urinary diversion and vaginal
      reconstruction using a colonic segment. The postoperative course was marked by
      prolapse of the neovagina requiring reoperation via a transvaginal approach. The
      modalities of this prolapse repair are described and the various possibilities
      for urinary diversion and vaginal reconstruction after pelvic exenteration in
      women are then discussed.

PMID- 10951943
TI  - [Seminal vesicle dystrophy as the cause of chronic unilateral pelvic pain in a 20
      year-old male].
AB  - The authors report on the case of a male patient referred for unilateral pelvic
      pain. An enlarged right seminal vesicle was showed by clinical examination and
      radiological technics. Total relief of symptoms was obtained by surgical
      excision. Pathological examination concluded on a dystrophic lesion of the
      seminal vesicle. Obstruction of the right ejaculatory duct, which could not be
      proved anyway is the most probable hypothesis.

PMID- 10951941
TI  - [Carcinomatous degeneration of augmentation enterocystoplasty].
AB  - Augmentation enterocystoplasties are performed increasingly frequently and their
      indications are no longer exclusively limited to small tuberculous bladders. One
      of the most serious complications of these procedures is malignant
      transformation, as reported in the present case. Carcinomatous degeneration is
      uncommon and usually occurs more than ten years after enterocystoplasty. Patients
      treated by this operation must be submitted to annual cystoscopy combined with
      guided biopsies at the slightest doubt. This surveillance should be started
      between the 5th and the 10th postoperative year.

PMID- 10951945
TI  - [Paratesticular rhabdomyosarcoma in the young adult].
AB  - The authors report a case of paratesticular thabdomyosarcoma in a young adult.
      This tumour is more frequent in children than in adults. Rhabdomyosarcoma is the
      commonest variety of soft tissue sarcoma in children and young adults. It
      represents 6.5% of all malignant tumours in paediatrics with an annual incidence
      of 4 to 7 cases/million children. The primary paratesticular site is considered
      to have a good prognosis in comparison with other rhabdomyosarcomas, despite the
      frequency of retroperitoneal lymph node invasion. This superficial site allows
      rapid diagnosis and consequently often complete resection of the tumour. The
      multidisciplinary treatment of paratesticular rhabdomyosarcoma has improved
      control of the disease with a 2-year survival of 80%.

PMID- 10951944
TI  - [Urethral rupture in penile fracture. Report of 2 cases].
AB  - In the light of two cases of fracture of the corpora cavernosa associated with
      rupture of the urethra and a review of the recent literature, the authors
      consider that early surgical treatment is useful and the only way of ensuring
      rapid recovery without sequelae.

PMID- 10951946
TI  - [Transatlantic view on tension-free vaginal tape].
AB  - T.V.T. is still presented as a minimally invasive operation, but this is not the
      case in all hands according to the various series reported at the recent EAU
      congress in Brussels. The indications are also still poorly defined and the long
      term effects of a synthetic, suburethral tension tape remain uncertain.

PMID- 10951947
TI  - [Plastic surgery of the penis after circumcision].
AB  - One of the possible complications of circumcision is excessive resection of
      penile skin. This technical note describes two penile plasty techniques using
      scrotal skin after excessive circumcision.

PMID- 10951948
TI  - Transmyocardial laser revascularization.
AB  - Transmyocardial laser revascularization is an alternative treatment option for
      patients with refractory angina who are not suitable candidates for more
      conventional coronary intervention or surgery. The laser creates channels that
      provide blood flow from the left ventricular chamber to areas of ischemic
      myocardium. Results have been impressive with patients reporting a reduction in
      angina of two classes according to the Canadian Heart Association Angina
      Classification. Care of the patient post transmyocardial laser revascularization
      procedure is comparable to that of other cardiac surgery patients. Innovations in
      this relatively new procedure include less invasive approaches and using it as an
      adjunctive or delivery modality for gene therapy.

PMID- 10951949
TI  - Cue sensitivity in women with cardiac disease.
AB  - The purpose of this study was to discover factors that influenced the healthcare
      seeking behavior of women cardiac patients. Interviews included 10 women with
      cardiac disease, two women at risk for cardiac disease, three advanced nurse
      practitioners, and one cardiologist. Participants were interviewed on two
      occasions. Taped transcripts were reviewed using a grounded theory approach.
      Analysis revealed a core process of cardiac cue sensitivity that originated in
      the period prior to entry into the healthcare system. The stages of this process
      included: cue apprehension, cue assimilation, and medical consultation. Cues were
      signs, symptoms, or self risk appraisal. Decisions to discount or attend to cues
      was dependent on the nature, intensity, and specificity of the cue to cardiac
      disease as well as the woman's knowledge and experience with cardiac disease and
      validation with others. A sensitivity to the subjective cue experiences of women
      and a recognition of public attitudes regarding women and cardiac disease
      facilitates their entry into the healthcare system and improves outcomes for
      women with cardiac disease.

PMID- 10951950
TI  - Development and testing of the Hill-Bone Compliance to High Blood Pressure
      Therapy Scale.
AB  - The Hill-Bone Compliance to High Blood Pressure Therapy Scale assesses patient
      behaviors for three important behavioral domains of high blood pressure
      treatment: 1) reduced sodium intake; 2) appointment keeping; and 3) medication
      taking. This scale is comprised of 14 items in three subscales. Each item is a
      four point Likert type scale. The content validity of the scale was assessed by a
      relevant literature review and an expert panel, which focused on cultural
      sensitivity and appropriateness of the instrument for low literacy. Internal
      consistency reliability and predictive validity of the scale were evaluated using
      two community based samples of hypertensive adults enrolled in clinical trials of
      high blood pressure care and control. The standardized alpha for the total scale
      were 0.74 and 0.84, and the average interitem correlations of the 14 items were
      0.18 and 0.28, respectively. The construct and predictive validity of the scale
      was assessed by factor analysis and by testing of theoretically derived
      hypotheses regarding whether the scale demonstrated consistent and expected
      relationships with related variables. In this study, high compliance scale scores
      predicted significantly lower levels of blood pressure and blood pressure
      control. Moreover, high compliance scale scores at the baseline were
      significantly associated with blood pressure control at both baseline and at
      follow up in the two independent samples. This brief instrument provides a simple
      method for clinicians in various settings to use to assess patients' self
      reported compliance levels and to plan appropriate interventions.

PMID- 10951951
TI  - A closer look at compliance research in heart failure patients in the last
      decade.
AB  - Compliance with a complex healthcare regimen is required of most patients with
      heart failure. Noncompliance with even some aspects of the recommended treatment
      can lead to repeated and preventable hospitalizations, or even death. This paper
      reviews the extent of noncompliance for general health-seeking behavior and
      recommended lifestyle modifications in the general population, as well as the
      research on compliance conducted specifically in patients with heart failure.
      Research findings are reviewed in three areas: the extent and predictors of
      compliance, the relationship of compliance and clinical outcomes, and
      interventions designed to increase compliance in heart failure patients. Based on
      research findings to date, strategies to enhance compliance are offered.

PMID- 10951952
TI  - Cardiovascular complications of HIV.

PMID- 10951953
TI  - Cardiovascular nursing in the United Kingdom.

PMID- 10951954
TI  - Has this patient lost his lead?

PMID- 10951955
TI  - Performance improvement: increasing recognition and treatment of postoperative
      delirium.

PMID- 10951956
TI  - [Flow cytometry, small cell populations and allergy].

PMID- 10951957
TI  - [Neutrophil polynuclear anticytoplasmic antibodies in systemic vasculitides].

PMID- 10951958
TI  - [Polynuclear basophils, the key to allergic reactions. Modulations by
      chemokines].
AB  - Both IgE synthesis and inflammatory cell recruitment are recognized to be major
      components of the allergic response, leading to bronchial inflammation.
      Typically, T cells are considered to be the key stone of the allergic reaction
      after acquisition of their TH2 phenotype, responsible for IL-4, -5, -10 -13
      production. Basophil is also capable to produce IL-4 and IL-13 following non
      specific or antigen activations, and chemokines induce basophil chemotaxis and
      inflammatory mediator release. However, in context of allergy, the contribution
      of basophil to cytokine production remains unclear, and the role of chemokine on
      it is not known. To address this issue, leucocytes from healthy and allergic
      asthmatic patients were incubated in presence of ionomycine or Ag extracts, with
      or without chemokine, then fixed, permeabilized, stained using antibodies anti
      IgE, anti-CD3, anti-cytokine, and analyzed by flow cytometry. After ionomycin
      activation, a large majority of basophils from both control and allergic
      asthmatic subjects express IL-4 and IL-13. Specific antigen induce cytokine
      expression by 5-20% of basophils from the asthmatic group only, and basophils
      represent 80% of IL-4 producing cells (p < 0.01). Basophil IL-4 expression peaks
      at 2 h (p < 0.01), whereas IL-13 expression is more delayed, suggesting that
      basophil may be involved in initiation, amplification and maintenance of allergic
      response. Since CD40 ligand is early up-regulated on peripheral blood basophils
      (p < 0.05), it may be critical in the initial IgE production. CC chemokines
      (eotaxin, eotaxin-2, RANTES, and MCP-2, 3, 4) enhance the frequency of IL-4
      producing basophils (p < 0.01), following Ag activation, and eotaxin lowers the
      Ag concentration responsible for IL-4 production by 40 fold (p < 0.01). These
      data demonstrate that after antigen activation, basophils are the predominant
      peripheral blood cells expressing IL-4 and IL-13, and add weight to the
      conclusions that basophils are envolved in the regulation of allergic diseases.
      Finally, our results describe a novel role for CC chemokine: the potentialisation
      of IL-4 expression, suggesting potential inovative approaches to treat allergic
      asthma.

PMID- 10951959
TI  - [Non-invasive ventilation in acute respiratory insufficiency].
AB  - Non invasive mechanical ventilation represents all the techniques of mechanical
      ventilation not using endotracheal connection to the respirator. Non invasive
      mechanical ventilation is essentially represented nowadays by facial (generally
      used for acute respiratory failure) and nasal ventilation (widely used for long
      term mechanical ventilation at home). Following in France the first studies of
      Rideau in the '80 in patients with chronic respiratory failure secondary to
      muscular dystrophy, Meduri, then Brochard demonstrated the interest of non
      invasive mechanical ventilation in the management of acute on chronic respiratory
      failure. A simple algorithm is thus able to recommend in first attempt use of non
      invasive mechanical ventilation in acute on chronic respiratory failure except if
      the patient presents in a severe respiratory status imposing in first line
      endotracheal ventilation. In parallel, more recent studies have demonstrated the
      interest of that technique in immediate ventilatory link in the spectrum of
      weaning of endotracheal mechanical ventilation. In hypoxic acute respiratory
      failure, non invasive mechanical ventilation remains controversial and seems to
      be better indicated in moderate to severe respiratory status.

PMID- 10951960
TI  - [Hospital information systems ineffectiveness in costing ambulatory chemotherapy
      in pulmonary oncology].
AB  - The real cost of medical consumption was compared with the proportion of
      medication consumption of (the) GHM n(o) 681 (homogeneous group of patients,
      chemotherapy for cancer in day care) in the French case mix system (PMSI). For
      those patients in our thoracic oncology unit (Sainte-Marguerite Hospital,
      Marseille, France), the real medication cost was calculated from prices paid by
      the hospital, then compared to the expected expenditures for the medication
      consumption of the GHM 681, i.e. 678 French francs (24.1% of the 225 ISA points
      (synthetic activity index)). Over a period of 2 months in 1998, 87 patients (mean
      age 63 +/- 11) had 194 chemotherapy sessions in day care, with multi-drug therapy
      in 38 cases. Vinorelbine or gemcitabine represented 81% of the single drug
      chemotherapy. In 84% of the single drug and 76% of the multi-drug chemotherapy,
      the real cost of medication consumption was above the allocated budget. The mean
      cost for single drug chemotherapy was 1722 FF and 2920 FF for multi-drug
      chemotherapy. The budget allocated by the PMSI shows a deficit in the most cases.
      To avoid a restriction in the use of some drugs, it appears that the French
      system of budget evaluation needs to be improved.

PMID- 10951961
TI  - [Body composition in chronic obstructive lung patients. Comparison of bioelectric
      impedance and anthropometry].
AB  - Malnutrition is associated with poor prognosis in patients with chronic
      obstructive pulmonary disease (COPD). Body weight is not a reliable evaluation
      criterium. Body composition which is more useful can be determined routinely
      using 2 techniques: skinfold thickness anthropometry (Ant) and bioelectrical
      impedance analysis (BIA). The validity of this last technique has not been
      demonstrated in patients with COPD. Fat-free mass (FFM) in 58 patients (51 men, 7
      women) with stable COPD (FEV1 < 50% of predicted value) was assessed using the 4
      skinfold-thickness method (Ant) and BIA (Imp). Statistical analysis included
      correlation analysis, intraclass correlation coefficient, and the Bland and
      Altman analysis. Imp-FFM and Ant-FFM correlated well (r = 0.920; p < 0.0001).
      Intraclass correlation coefficient was high (rI = 0.9065). However, the values
      were scattered and there was a systematic bias (significant linear regression
      between the difference in estimates obtained by the 2 methods and the means). As
      anthropometric measurements are not reliable in the elderly patients, our results
      suggest that BIA could be a useful tool to determine FFM in patients with COPD.
      Its validity still has to be tested against a reference method.

PMID- 10951962
TI  - [Smoking knowledge, attitudes, and behaviors of patients in Morocco].
AB  - Smoking is a serious public health problem. In Morocco, the number of smokers
      varies from 24% to 52% depending on different social categories (school children,
      university students, public health workers, industrial workers, civil servants).
      The aim of our descriptive study was to analyze knowledge about smoking and
      smoking habits in patients hospitalized or followed by two units in the Ibn Rochd
      Hospital, cardiology and respiratory diseases. A questionnaire was given to a
      consecutive series of 200 patients between January and March 1997 (100 patients
      in each unit). Twenty percent of the patients were smokers and 23% were former
      smokers. The most well known health risks of smoking in the two groups of
      patients were respiratory and cardiovascular risks (88% and 71% respectively).
      Smokers and former smokers were more aware of these health risks. 86% of the
      smokers and former smokers had attempted to stop smoking at least once, mainly
      for a "health" reasons. 60% of smokers and former smokers decided to never smoke
      or never take a cigarette again. 66% of the patients said they had not been
      advised at the hospital about the risk of smoking. Our study provides a basis for
      further studies. It points out the importance of the smoking phenomena and the
      minimal role played by health personnel in advising patients. Health care workers
      should participate in antismoking activities during their consultation activities
      at the hospital in order to help patients stop smoking and also help implement
      rigorous antismoking laws in Morocco.

PMID- 10951963
TI  - [Rare pulmonary complication in intravesical BCG treatment].
AB  - We report a case of epithelioid granulomatous allergic lung disease in a patient
      given intra-bladder BCG therapy for treatment of a tumor. This uncommon
      complication is sometimes related to bacterial dissemination or to an
      immunoallegic reaction occurring from the third to eigth week after onset of the
      instillation. Clinically, the patient presents a flu-like syndrome. The standard
      chest X-ray followed by computed tomography, demonstrates the extension of the
      pulmonary lesions. Miliary dissemination is rarely reported (10 cases in the
      literature). Histological proof can be obtained from an endoscopic bronchial
      biopsy or a surgical specimen of the pulmonary parenchyma. Treatment is based on
      corticosteroid therapy in combination with antituberculosis antibiotics.
      Prognosis is generally good with treatment.

PMID- 10951964
TI  - [Chronic necrotizing pulmonary aspergillosis and ankylosing spondylarthritis].
AB  - Fibro-bullous disease is a late complication of ankylosing spondylarthritis. Its
      radiologic features frequently mimics tuberculosis or excavated neoplasm. About
      50 to 65% of patients with ankylosing spondylarthritis have chronic aspergillus
      colonization of their airways. Pulmonary aspergillosis infection occurs in 10 to
      30% during evolution. We report two cases of patients with spondylarthritis who
      developed chronic necrotizing pulmonary aspergillosis. Diagnosis was based on
      serology, mycologic examination of expectoration and in one case on histology
      obtain by transbronchial biopsies. Pulmonary complications due to aspergillus
      species frequently reveal an associated fibro-bullous disease in patients with
      ankylosing spondylarthritis. This can be reported to diminished chest wall
      movements in such patients. Treatment is based on administration of anti-fungal
      drugs. In case of medical treatment failure, thoracic surgery may be indicated.

PMID- 10951965
TI  - [Pulmonary hypertension in patient with beta-thalassemia major].
AB  - We report a case of pulmonary hypertension (PH) in a 35-year old patient with
      beta-thalassemia major; he had commenced blood transfusions after the age of 4
      years and had been splenectomised at the age of 6 years. PH clinical presentation
      was not uncommon. Hemodynamic study revealed precapillary PH with high cardiac
      output; vasodilators agents led to significant pulmonary responsiveness. In beta
      thalassemia, whereas congestive heart failure is common and due to cardiac
      hemosiderin deposition, PH appears to be non rare but its etiopathogenic
      mechanism remain unclear and probably non univoqual. Hypoxemia as well as
      hemodynamic changes related to chronic anemia including increased pulmonary flow
      might play an important role. Management should include blood transfusions to
      correct anemia, the indication and the choice of vasodilator agents need to be
      evaluated.

PMID- 10951966
TI  - [Pasteurella multocida lung abscess. Study of a case with demonstration of a cat
      as vector].
AB  - We report a case of a lung abscess due to Pasteurella multocida, isolated from
      bronchial secretions by fiberoptic bronchoscopy. Antibodies against Pasteurella
      multocida were elevated in the patient, and absent in controls (including the
      patient's wife). The identity of the strain isolated in the patient and that in
      his cat was proved by molecular method using pulsed field gel electrophoresis.

PMID- 10951967
TI  - [Multiple pulmonary hydatidosis with floating balloon appearance and cardiac
      localization].
AB  - Multiple hydatidosis in a thoracic localization is unusual and a cardiac
      localization very exceptional. We report a case of multiple hydatidosis greatly
      improved by medical treatment with albendazole which was associated with a
      cardiac cyst successfully treated by surgical resection. No recurrence has been
      observed at 4 year follow-p. We point out therapeutic management options in these
      unusual forms of the disease.

PMID- 10951968
TI  - [Lipid pneumonia and pleural-pulmonary atypical mycobacteriosis].
AB  - We report a case of fat deposit pneumonia extending to the parietal pleura with a
      granulomatous reaction centered on the fat vaculoles. This case was complicated
      by an atypical and fatal mycobacterial infection caused by Mycobacterium
      chelonae. The severity of Mycobacterium chelonae infection in fat deposit
      pneumonia warrants early empirical antibiotic therapy.

PMID- 10951969
TI  - [Lung opacities of an unusual cause].

PMID- 10951970
TI  - [Medical ethics and therapeutic progress: the example of lung cancers. Help,
      Hippocrates!].

PMID- 10951971
TI  - [Monitoring patient treated by continuous positive pressure: recommendations of
      the SPLF group].

PMID- 10951972
TI  - In vitro evaluation of intraluminal factors that may alter intestinal
      permeability in ponies with carbohydrate-induced laminitis.
AB  - OBJECTIVES: To study the in vitro effects of cecal contents incubated with corn
      starch on colonic permeability in horses. ANIMALS: 4 healthy adult ponies.
      PROCEDURE: Mucosal specimens were obtained from the right ventral colon and
      mounted in Ussing chambers. Changes in short circuit current, conductance, and
      large-molecule permeability in response to addition of cecal contents and cecal
      contents incubated with corn starch were evaluated for 120 minutes. RESULTS:
      Incubation of cecal contents with corn starch for 8 hours resulted in a decrease
      in cecal content pH and an increase in lactic acid concentration. These changes
      were similar to those reported in vivo for ponies given corn starch. Exposure of
      colonic mucosa to cecal contents incubated with corn starch resulted in an
      increase in tissue conductance and permeability of technetium Tc 99m pentetate,
      compared with mucosa exposed to cecal contents alone. CONCLUSIONS AND CLINICAL
      RELEVANCE: In vitro exposure of colonic mucosa to cecal contents incubated with
      starch resulted in increased paracellular permeability. Fermentation of excessive
      amounts of carbohydrate in the intestinal lumen of horses may directly induce
      increased intestinal permeability associated with carbohydrate-induced laminitis.

PMID- 10951973
TI  - Laminar microvascular flow, measured by means of laser Doppler flowmetry, during
      the prodromal stages of black walnut-induced laminitis in horses.
AB  - OBJECTIVE: To measure changes in laminar microvascular blood flow (LMBF) over
      time in healthy horses and horses in the prodromal stage of black walnut-induced
      laminitis and to determine the effects of glyceryl trinitrate application on LMBF
      in horses with acute laminitis. ANIMALS: 10 healthy adult horses. PROCEDURE:
      Laser Doppler flowmetry was used to measure LMBF Baseline measurements were
      obtained, horses were given deionized water via a nasogastric tube, and
      measurements were obtained hourly for 12 hours. Twenty-four hours later, baseline
      measurements were again obtained, and horses were given black walnut extract.
      Measurements were obtained hourly for 12 hours or until development of Obel grade
      3 laminitis. At this time, 5 horses were treated with phenylbutazone, and the
      other 5 were treated with phenylbutazone and glyceryl trinitrate, and
      measurements were obtained hourly for an additional 12 hours. RESULTS: LMBF was
      significantly decreased 1 and 2 hours after administration of the black walnut
      extract but then returned to near-baseline values for the next 6 hours. Eight
      hours after extract administration, there was a second significant decrease in
      LMBF that persisted until the end of the study. Glyceryl trinitrate had no effect
      on LMBF. Clinical signs of laminitis developed 8 to 12 hours after extract
      administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in
      horses with black walnut-induced laminitis, there is an early decrease in LMBF
      followed by reperfusion prior to onset of clinical signs. Treatment with glyceryl
      trinitrate after development of clinical signs of laminitis did not have a
      significant effect on LMBF.

PMID- 10951974
TI  - Effect of hemodialysis on plasma amino acid concentrations in healthy dogs.
AB  - OBJECTIVE: To characterize the effect of maintenance hemodialysis on plasma amino
      acid concentrations and to quantitate free amino acid losses into the dialysate
      during hemodialysis in healthy dogs. ANIMALS: 8 healthy adult dogs. PROCEDURE:
      Five dogs received hemodialysis treatments 3 times per week for 4 weeks. Plasma
      amino acid concentrations were evaluated once per week for 4 weeks in each of the
      5 dogs prior to hemodialysis (time 0), 90 minutes during hemodialysis, and
      immediately after hemodialysis (180 minutes). Total free amino acid
      concentrations and plasma amino acid concentrations (time 0, 90 minutes, and 180
      minutes) in the dialysate were evaluated in 3 dogs that received 1 hemodialysis
      treatment. RESULTS: Significant time versus week interactions with any plasma
      amino acid were not detected; however, significant decreases in all plasma amino
      acid concentrations measured were detected at the midpoint of dialysis (46 +/-
      2%) and at the end of each dialysis session (38 +/- 2%). Mean (+/- SEM) total
      free amino acid loss into the dialysate was 2.7 +/- 0.2 g or 0.12 g/kg of body
      weight. CONCLUSIONS AND CLINICAL RELEVANCE: Hemodialysis is associated with
      significant alterations in plasma amino acid concentrations and loss of free
      amino acids into the dialysate. Loss of amino acids into the dialysate, coupled
      with protein calorie malnutrition in uremic patients, may contribute to depletion
      of amino acid stores.

PMID- 10951975
TI  - Altered expression of G proteins in thyroid gland adenomas obtained from
      hyperthyroid cats.
AB  - OBJECTIVE: To determine whether expression of G proteins (G(i) and G(s)) is
      altered in thyroid gland adenomas obtained from hyperthyroid cats. SAMPLE
      POPULATION: Adenomatous thyroid glands obtained from 8 hyperthyroid cats and
      thyroid glands obtained from 4 age-matched euthyroid cats. PROCEDURE: Expression
      of G(i) and G(s) was quantified in enriched membrane preparations of thyroid
      gland tissue, using immunoblotting with G(i) and G(s) antibodies and toxin
      catalyzed ADP-ribosylation. RESULTS: Expression of G(i) was significantly reduced
      in thyroid gland adenomas from hyperthyroid cats, compared with normal thyroid
      gland tissue from euthyroid cats. Expression of G(s) was similar between the 2
      groups. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in expression of G in
      adenomatous thyroid glands of cats may reduce the negative inhibition of the cAMP
      cascade in thyroid cells, leading to autonomous growth and hypersecretion of
      thyroxine. Understanding the molecular mechanisms for hyperthyroidism in cats may
      lead to better treatment or, ultimately, prevention of the disease.

PMID- 10951976
TI  - Effects of an extract of Serenoa repens on dogs with hyperplasia of the prostate
      gland.
AB  - OBJECTIVE: To determine effects of an extract of Serenoa repens on dogs with
      prostatic hyperplasia. ANIMALS: 20 mature male dogs with benign prostatic
      hyperplasia. PROCEDURE: Dogs were assigned to 3 comparable groups on the basis of
      prostatic volume per kg of body weight and degree of prostatic hyperplasia
      determined histologically. Dogs in 2 groups were treated for 91 days (8 received
      500 mg, PO, q 8 h [1,500 mg/d], and 6 received 100 mg, PO, q 8 h [300 mg/d]). The
      control group of 6 dogs did not receive medication. Effects of treatment on
      prostatic volume, prostatic weight, prostatic histologic characteristics,
      radiographic and ultrasonographic assessment of prostatic size, results of CBC,
      serum biochemical analyses, and urinalysis, serum testosterone concentration, and
      semen characteristics were determined. At the termination of the study, all dogs
      were euthanatized, and necropsies were performed. Investigators conducting tests
      and interpreting results were not aware of treatment group of each dog. RESULTS:
      Treatment did not affect prostatic weight, prostatic volume, or prostatic
      histologic scores, libido, semen characteristics, radiographs of the caudal
      portion of the abdomen, prostatic ultrasonographs, or serum testosterone
      concentrations. Results of CBC, serum biochemical analyses or urinalysis, and
      body weights did not change during treatment. CONCLUSIONS AND CLINICAL RELEVANCE:
      Treatment with an extract of S repens for 91 days did not significantly affect
      the prostate gland of dogs. Adverse effects were not evident. Although products
      containing extracts of S repens are widely advertised for men with prostatic
      hyperplasia, beneficial or harmful effects of this plant extract were not found
      in dogs with prostatic hyperplasia.

PMID- 10951977
TI  - Effects of dietary antioxidant supplementation on oxidative damage and resistance
      to oxidative damage during prolonged exercise in sled dogs.
AB  - OBJECTIVES: To determine effects of dietary antioxidant supplementation on plasma
      concentrations of antioxidants, exercise-induced oxidative damage, and resistance
      to oxidative damage during exercise in Alaskan sled dogs. ANIMALS: 62 Alaskan
      sled dogs. PROCEDURE: Dogs were matched for age, sex, and ability and assigned to
      1 of 3 groups: sedentary and nonsupplemented (control [C]; n = 21), exercised and
      supplemented (S; 22), and exercised and nonsupplemented (N; 19). Dogs in group S
      were given 400 units of alpha-tocopherol acetate, 3 mg of beta-carotene, and 20
      mg of lutein orally per day for 1 month, then dogs in groups S and N completed 3
      days of exercise. Blood samples were collected before and after 1 and 3 days of
      exercise and after 3 days of rest. Plasma antioxidant concentrations were
      determined, and oxidative damage to DNA (plasma 7,8 dihydro-8-oxo
      2'deoxyguanosine [8-oxodG] concentration) and membrane lipids (plasma
      hydroperoxide concentration) and resistance of plasma lipoproteins to oxidation
      were assessed. RESULTS: Supplementation increased plasma concentrations of alpha
      tocopherol, beta-carotene, and lutein. Plasma concentration of alpha-tocopherol
      increased and concentration of lutein decreased in group S with exercise.
      Concentration of 8-oxodG decreased in group S but increased in group N during and
      after exercise. Lag time of in vitro oxidation of lipoprotein particles increased
      with exercise in group S only. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary
      supplementation with antioxidants resulted in increased plasma concentrations of
      antioxidants. Moreover, supplementation decreased DNA oxidation and increased
      resistance of lipoprotein particles to in vitro oxidation. Antioxidant
      supplementation of sled dogs may attenuate exercise-induced oxidative damage.

PMID- 10951978
TI  - Effects of intranasal inoculation of porcine reproductive and respiratory
      syndrome virus, Bordetella bronchiseptica, or a combination of both organisms in
      pigs.
AB  - OBJECTIVE: To examine effects of co-infection with porcine reproductive and
      respiratory syndrome virus (PRRSV) and Bordetella bronchiseptica in pigs.
      ANIMALS: Forty 3-week-old pigs. Procedure-30 pigs (10 pigs/group) were inoculated
      with PRRSV, B bronchiseptica, or both. Ten noninoculated pigs were control
      animals. RESULTS: Clinical signs, febrile response, and decreased weight gain
      were most severe in the group inoculated with both organisms. The PRRSV was
      isolated from all pigs in both groups inoculated with virus. All pigs in both
      groups that received PRRSV had gross and microscopic lesions consistent with
      interstitial pneumonia. Bordetella bronchiseptica was cultured from all pigs in
      both groups inoculated with that bacterium. Colonization of anatomic sites by B
      bronchiseptica was comparable between both groups. Pigs in the group that
      received only B bronchiseptica lacked gross or microscopic lung lesions, and B
      bronchiseptica was not isolated from lung tissue. In the group inoculated with B
      bronchiseptica and PRRSV, 3 of 5 pigs 10 days after inoculation and 5 of 5 pigs
      21 days after inoculation had gross and microscopic lesions consistent with
      bacterial bronchopneumonia, and B bronchiseptica was isolated from the lungs of 7
      of those 10 pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical disease was
      exacerbated in co-infected pigs, including an increased febrile response,
      decreased weight gain, and B bronchiseptica-induced pneumonia. Bordetella
      bronchiseptica and PRRSV may circulate in a herd and cause subclinical
      infections. Therefore, co-infection with these organisms may cause clinical
      respiratory tract disease and leave pigs more susceptible to subsequent infection
      with opportunistic bacteria.

PMID- 10951979
TI  - Comparison of Northern blot hybridization and a reverse transcriptase-polymerase
      chain reaction technique for measurement of mRNA expression of metalloproteinases
      and matrix components in articular cartilage and synovial membrane from horses
      with osteoarthritis.
AB  - OBJECTIVE: To determine relative amounts of mRNA expression of aggrecan, type-II
      collagen, matrix metalloproteinase (MMP) 1, and MMP3 in articular cartilage and
      synovial membrane samples from healthy equine joints and joints with
      osteoarthritis (OA) and to compare results of Northern blot hybridization with
      results of a reverse transcriptase-polymerase chain reaction (RT-PCR) assay.
      SAMPLE POPULATION: Articular cartilage samples from 8 pairs of joints (1 with OA
      and 1 healthy) from 6 horses and synovial membrane samples from 6 pairs of joints
      from 5 horses. PROCEDURE: RNA was extracted from samples by use of a modified
      Trizol procedure. Northern blot hybridization and the RT-PCR assay were
      performed; results were quantitated by use of glyceraldehyde 3-phosphate
      dehydrogenase as an internal standard. RESULTS: Articular cartilage samples from
      joints with mild or moderate OA yielded less total RNA than samples from joints
      with severe OA. Northern blot hybridization indicated that type-II collagen mRNA
      expression in articular cartilage samples from joints with OA was significantly
      greater than expression in samples from healthy joints. The RT-PCR assay
      identified low levels of MMP3 mRNA expression in 4 of 8 sets of articular
      cartilage samples and 4 of 6 sets of synovial membrane samples, whereas Northern
      blot hybridization identified MMP3 mRNA expression in only 1 of 6 sets of
      articular cartilage samples and 1 of 6 sets of synovial membrane samples.
      CONCLUSIONS: A RT-PCR assay is more sensitive than Northern blot hybridization
      for detection of MMP3 mRNA expression in articular cartilage and synovial
      membrane and requires smaller samples.

PMID- 10951980
TI  - Comparison of the in vitro antiproliferative effects of five immunosuppressive
      drugs on lymphocytes in whole blood from cats.
AB  - OBJECTIVE: To compare the in vitro immunosuppressive effects of cyclosporine and
      4 novel immunosuppressive drugs on lymphocytes in whole blood collected from
      healthy cats. SAMPLE POPULATION: Whole blood samples collected from 10 healthy
      adult domestic shorthair cats. PROCEDURE: Mitogen-stimulated lymphocyte
      proliferation in whole blood incubated with and without various concentrations of
      cyclosporine, tacrolimus, sirolimus, mycophenolic acid (MPA), or A771726 was
      measured by use of [3H]thymidine incorporation. Drug concentrations that resulted
      in a 50% inhibition of mitogen-induced proliferation (IC50) were calculated.
      Lymphocyte viability was determined by use of the trypan blue dye exclusion
      method. RESULTS: An obvious dose-response relationship for the antiproliferative
      effects of each drug was detected. Mean IC50 determined with concanavalin A was
      46 nM for cyclosporine, 9 nM for tacrolimus, 12 nM for sirolimus, 16 nM for MPA,
      and 30 mM for A771726, whereas with pokeweed mitogen, mean IC50 was 33 nM for
      cyclosporine, 5 nM for tacrolimus, 15 nM for sirolimus, 14 nM for mycophenolic
      acid, and 25 mM for A771726. Mitogen-stimulated and nonstimulated lymphocytes
      remained viable, regardless of drug evaluated. CONCLUSIONS AND CLINICAL
      RELEVANCE: Tacrolimus, sirolimus, MPA, and A771726 inhibited in vitro mitogen
      stimulated proliferation of feline lymphocytes in a dose-dependent manner. These
      novel immunosuppressive drugs may be useful for management of immune-mediated
      inflammatory diseases and prevention and treatment of rejection in cats that
      undergo organ transplantation.

PMID- 10951981
TI  - Effect of daily floor treatment with sodium bisulfate on the fly population of
      horse stalls.
AB  - OBJECTIVE: To determine application rate and effectiveness of sodium bisulfate to
      decrease the fly population in a horse barn environment. SAMPLE POPULATION: 12
      privately owned farms in southeastern Pennsylvania. PROCEDURE: Application rates
      of sodium bisulfate were approximately 2.3 kg/stall, 1.1 kg/stall, and 0.5
      kg/stall. Two or 3 stalls were treated, and 1 or 2 stalls were not treated
      (control stalls) at each farm. Farm personnel applied sodium bisulfate in treated
      stalls daily for 7 days. Fly tapes were hung from the same site in treated and
      control stalls. After 24 hours, the fly tape was removed, flies adhering to the
      sticky surface were counted and recorded, and a new fly tape was hung. This
      procedure was repeated daily during each of the testing periods. RESULTS:
      Following the application of 2.3 kg of sodium bisulfate/stall, the numbers of
      flies collected on the fly tape were significantly decreased in treated stalls,
      compared with control stalls during the same time periods on 9 of the 12 farms
      evaluated. Following the application of 1.1 kg of sodium bisulfate/stall, fly
      numbers were significantly decreased in treated stalls on 6 of the 9 farms
      evaluated. Following the application of 0.5 kg of sodium bisulfate/stall, fly
      numbers were significantly decreased in the treated stalls on 3 of the 4 farms
      evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that sodium
      bisulfate would be effective for fly control in horse barns.

PMID- 10951982
TI  - Pharmacokinetics of erythromycin estolate and erythromycin phosphate after
      intragastric administration to healthy foals.
AB  - OBJECTIVE: To determine pharmacokinetics and plasma concentrations of
      erythromycin and related compounds after intragastric administration of
      erythromycin phosphate and erythromycin estolate to healthy foals. ANIMALS: 11
      healthy 2- to 6-month-old foals. PROCEDURE: Food was withheld from foals
      overnight before intragastric administration of erythromycin estolate (25 mg/kg
      of body weight; n = 8) and erythromycin phosphate (25 mg/kg; 7). Four foals
      received both drugs with 2 weeks between treatments. Plasma erythromycin
      concentrations were determined at various times after drug administration by use
      of high-performance liquid chromatography. Maximum plasma peak concentrations,
      time to maximum concentrations, area under plasma concentration versus time
      curves, half-life of elimination, and mean residence times were determined from
      concentration versus time curves. RESULTS: Maximum peak concentration of
      erythromycin A after administration of erythromycin phosphate was significantly
      greater than after administration of erythromycin estolate (2.9 +/- 1.1 microg/ml
      vs 1.0 +/- 0.82 microg/ml). Time to maximum concentration was shorter after
      administration of erythromycin phosphate than after erythromycin estolate (0.71
      +/- 0.29 hours vs 1.7 +/- 1.2 hours). Concentrations of anhydroerythromycin A
      were significantly less 1 and 3 hours after administration of erythromycin
      estolate than after administration of erythromycin phosphate. CONCLUSIONS AND
      CLINICAL RELEVANCE: Plasma concentrations of erythromycin A remained > 0.25
      microg/ml (reported minimum inhibitory concentration for Rhodococcus equi) for at
      least 4 hours after intragastric administration of erythromycin phosphate or
      erythromycin estolate, suggesting that the recommended dosage for either
      formulation (25 mg/kg, q 6 h) should be adequate for treatment of R equi
      infections in foals.

PMID- 10951984
TI  - Serum feline trypsin-like immunoreactivity following administration of ceruletide
      to healthy cats.
AB  - OBJECTIVE: To determine changes in serum feline trypsin-like immunoreactivity
      (fTLI) in response to administration of ceruletide to healthy cats. ANIMALS: 11
      healthy cats. PROCEDURES: Serum fTLI was determined, using a radioimmunoassay,
      before and 10, 20, 30, 40, and 50 minutes after IM administration of ceruletide
      (0.3 mg/kg [0.14 mg/lb]). RESULTS: Mean +/- SD baseline serum fTLI was 23.1 +/-
      4.1 mg/L. There was a statistically significant, but clinically unimportant,
      increase in serum fTLI 10 and 30 minutes after ceruletide administration.
      CONCLUSIONS AND CLINICAL RELEVANCE: In healthy cats, administration of ceruletide
      induced a statistically significant, but clinically unimportant, increase in
      serum fTLI. Whether responses in cats with exocrine pancreatic disorders would be
      different is unknown, but results suggest that a ceruletide stimulation test
      would likely not be useful for differentiating between healthy cats and cats with
      subclinical chronic exocrine pancreatic disorders.

PMID- 10951983
TI  - Determination of the cDNA sequence and mRNA expression of interleukin-1 receptor
      antagonist in horses.
AB  - OBJECTIVE: To determine the complementary DNA (cDNA) sequence of interleukin-1
      receptor antagonist (IL-1ra) in horses and compare messenger RNA (mRNA)
      expression of IL-1ra among horses of various breeds. SAMPLE POPULATION: Blood
      samples from neonatal and adult horses examined for a variety of diseases.
      PROCEDURE: A polymerase chain reaction procedure was used to amplify a 220 base
      pair (bp) portion of the genomic DNA. The upstream and downstream regions of the
      cDNA sequence were determined by means of 5' and 3' rapid amplification of cDNA
      ends (RACE) procedures. Northern blot hybridization was used to examine steady
      state mRNA expression of IL-1ra. RESULTS: The consensus sequence of the cDNA
      obtained with the 5'-RACE procedure and the sequence for the 220 bp portion of
      the genomic DNA represented the putative sequence for secreted IL-1ra. The
      predicted secreted IL-1ra amino acid sequence contained 176 residues with an in
      frame stop codon; the N-terminal 25 amino acid residues resembled the signal
      peptide reported for human secreted IL-1ra. An approximately 1.3 kilobase pair
      (kb) band that represented a portion of the 3' end of the coding region and the
      3' untranslated region was obtained by use of the 3' -RACE procedure. Northern
      blot hybridization detected a 1.6 kb transcript in blood RNA from adult Arabian,
      Belgian, Thoroughbred, and Standardbred horses. CONCLUSIONS: Results suggest that
      the DNA for equine secreted IL-1ra has a short (29 bp) 5' untranslated region, a
      534 bp coding region, and a long (approximately 1,080 bp) untranslated region.

PMID- 10951985
TI  - Prevalence of papillomatous digital dermatitis among culled adult cattle in the
      southeastern United States.
AB  - OBJECTIVE: To determine prevalence of papillomatous digital dermatitis (PDD)
      among culled adult dairy and beef cattle in the southeastern United States.
      ANIMALS: 815 cattle examined during 4 visits to a slaughterhouse. PROCEDURE: The
      left hind foot of each animal was examined for gross lesions of PDD. Breed and
      sex of the animals were recorded. Lesions were examined histologically for
      pathologic changes and bacteria, especially spirochetes. RESULTS: 22 of 76 (29%)
      dairy cattle and 29 of 739 (4%) beef cattle had gross lesions of PDD. Detection
      of lesions was not associated with sex of dairy cattle, but male beef cattle were
      more likely to have lesions of PDD than were female beef cattle. Histologically,
      acute and chronic lesions were seen; the most severe changes were localized to
      the stratum corneum. Spirochetes were seen in lesions from 31 of 51 (61%) cattle.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PDD is common among
      culled adult cattle. Prevalence was higher in culled adult dairy cattle than in
      culled adult beef cattle.

PMID- 10951986
TI  - Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane
      anesthetized rhesus monkeys (Macaca mulatta).
AB  - OBJECTIVE: To determine pharmacokinetics and selected cardiopulmonary effects of
      fentanyl in isoflurane-anesthetized rhesus monkeys. ANIMALS: 6 adult male rhesus
      monkeys. PROCEDURE: Fentanyl (8 mg/kg of body weight, IV) was administered to 6
      monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and
      esophageal temperature were kept constant, and ventilation was mechanically
      assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and
      fentanyl concentrations were determined before and for 8 hours after
      administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of
      noncompartmental methods based on statistical moment theory. RESULTS: Heart rate
      and mean arterial pressure decreased transiently following fentanyl
      administration. Maximal decreases were observed 5 to 15 minutes after
      administration. Arterial pH, Paco2, and Pao2 ranged from 7.46 +/- 0.04 to 751 +/-
      0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/- 105.3 to 482.9 +/-
      71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of
      distribution steady state, mean residence time, area under the curve, elimination
      rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 70
      +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 + 0.001/min,
      and 192.0 +/- 33.5 min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      Transient but potentially clinically important decreases in heart rate and mean
      arterial pressure were observed following fentanyl administration. Distribution
      and clearance data were similar to those reported for dogs and humans.

PMID- 10951987
TI  - Comparison of two heavy metal chelators for treatment of lead toxicosis in
      cockatiels.
AB  - OBJECTIVE: To compare efficacy and safety of meso-2,3-dimercaptosuccinic acid
      (DMSA) and Ca EDTA for treatment of experimentally induced lead toxicosis in
      cockatiels (Nymphicus hollandicus). ANIMALS: 137 (69 females, 68 males) healthy
      cockatiels between 6 months and 8 years old. PROCEDURE: Lead toxicosis was
      induced by placing lead shot in the gastrointestinal tract. Treatment with Ca
      EDTA (40 mg/kg of body weight, IM, q 12 h), DMSA (40 or 80 mg/kg, PO, q 12 h),
      and sodium sulfate salts (SSS; 0.5 mg/kg, PO, q 48 h) was initiated 4 days after
      induction of lead toxicosis. Blood lead concentrations were determined, using
      atomic absorption spectrophotometry. Number of birds surviving and blood lead
      concentrations were compared among groups. RESULTS: In Phase II of the study,
      administration of DMSA and Ca EDTA significantly decreased blood lead
      concentrations when used alone or in combination in birds with lead toxicosis.
      Addition of SSS did not result in further decreases in lead concentrations. Eight
      of 12 (66.7%) birds without lead toxicosis given 80 mg of DMSA/kg did not survive
      to the end of the study. Lesions related to treatment with chelating agents were
      not detected during necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: DMSA and Ca
      EDTA are effective chelating agents in cockatiels. Because DMSA is administered
      orally, it may be easier than other chelating agents for bird owners to
      administer at home. However, the narrow margin of safety of DMSA indicates that
      this agent should be used with caution.

PMID- 10951988
TI  - Use of a nonionic detergent (Triton WR 1339) in healthy cats to assess hepatic
      secretion of triglyceride.
AB  - OBJECTIVE: To determine whether a nonionic detergent (Triton WR 1339) can be used
      in cats to assess hepatic secretion of triglyceride. ANIMALS: 28 healthy cats.
      PROCEDURE: Triton WR 1339 was administered IV according to the following
      schedule: 5, 50, 150, and 250 mg/kg of body weight. Control cats did not receive
      an injection or received 0.9% NaCl or PBS solutions at the same osmolarity and
      volume as the 250 mg/kg group. Blood samples were collected throughout the 48
      hour period after administration for determination of triglyceride and
      cholesterol concentrations and for RBC morphology and osmotic fragility studies.
      RESULTS: Administration of Triton WR 1339 at 150 and 250 mg/kg caused profound
      hypertriglyceridemia. Triglyceride concentrations increased in a curvilinear
      fashion for the first 2 hours and remained increased for approximately 24 hours.
      Area under the time-concentration curve for triglyceride at 5 hours differed
      significantly among groups. At 12 and 24 hours, cholesterol was significantly
      higher in cats receiving 250 mg/kg. The most dramatic changes in osmotic
      fragility and RBC morphology were in cats receiving 250 mg/kg; 1 of these cats
      developed severe icterus and died 5 days later. Feeding rice and casein before
      administering Triton WR 1339 at 150 mg/kg did not appear to affect the
      hypertriglyceridemia response. CONCLUSIONS AND CLINICAL RELEVANCE: Triton WR 1339
      can be administered IV to cats at a rate of 150 mg/kg to assess hepatic
      triglyceride secretion, although some cats may have increased RBC osmotic
      fragility. Higher dosages caused substantial adverse effects, whereas lower
      dosages did not alter plasma triglyceride concentration.

PMID- 10951989
TI  - Phagocytosis and killing of Staphylococcus aureus by bovine neutrophils after
      priming by tumor necrosis factor-alpha and the des-arginine derivative of C5a.
AB  - OBJECTIVES: To evaluate effects of proinflammatory mediators on phagocytosis and
      killing of Staphylococcus aureus, the oxidative burst (OB), and expression of
      receptors for opsonins by bovine neutrophils. SAMPLE POPULATION: Neutrophils from
      10 cattle. PROCEDURE: Neutrophils were primed with recombinant bovine tumor
      necrosis factor-alpha (TNF-alpha) or the des-arginine derivative of bovine C5a
      (C5a(desArg)) and mixed with S aureus. Phagocytosis and OB were measured by use
      of flow cytometry. Rate of phagocytosis and intracellular killing were evaluated.
      Expression of receptors for immunoglobulins and the C3bi fragment of complement
      were estimated by use of flow cytometry. RESULTS: Priming of neutrophils by TNF
      alpha improved phagocytosis of S aureus with a concentration-dependent effect.
      Phagocytosis of preopsonized washed bacteria was increased by activation of
      neutrophils with C5a(desArg). Phagocytosis was optimal when neutrophils primed
      with TNF-alpha were activated with C5a(desArg). The OB of phagocytizing
      neutrophils was highest when TNF-alpha and C5a(desArg) were used in combination.
      Bactericidal activity of neutrophils was stimulated by priming with TNF-alpha or
      C5a(desArg). Binding of bovine IgM or IgG2 to bovine neutrophils was not
      stimulated byTNF-alpha, C5a(desArg), or both, and aggregated IgG1 did not bind to
      neutrophils regardless of their activation state. Both TNF-alpha and C5a(desArg)
      increased expression of beta2 integrins (CD18), with the highest expression when
      they were used in combination. CONCLUSIONS AND CLINICAL RELEVANCE: The mediators
      TNF-alpha and C5a(desArg) stimulated phagocytic killing by neutrophils and
      potentiated each other when used at suboptimal concentrations. Bovine neutrophils
      have enhanced bactericidal activities at inflammatory sites when TNF-alpha,
      C5a(desArg), or both are produced locally.

PMID- 10951990
TI  - Effects of clomipramine hydrochloride on heart rate and rhythm in healthy dogs.
AB  - OBJECTIVE: To determine the effects of clomipramine hydrochloride on heart rate
      and rhythm in dogs. ANIMALS: 17 healthy Beagles. PROCEDURES: In experiment 1, 8
      dogs received placebo or clomipramine (20 mg/kg of body weight, q 24 h, PO) for 7
      days in a 2-way crossover design. In experiment 2, 9 dogs were evaluated for 48
      hours before and 24 hours after oral administration of clomipramine (4 or 12
      mg/kg) in a 2-way crossover design. Electrocardiogram and heart rate were
      monitored continuously by use of telemetry. RESULTS: A significant diurnal rhythm
      in heart rate was detected; minimum values were recorded at night. Administration
      of 20 mg of clomipramine/kg induced a significant reduction in heart rate, with
      peak effect achieved approximately 12 hours after dosing. Administration of 4 or
      12 mg of clomipramine/kg did not result in significant changes in heart rate.
      Sinoatrial and second-degree atrioventricular block and ventricular escape beats
      were observed during periods of slow heart rate in more dogs that received
      clomipramine (3 to 4 of 8 dogs), compared with dogs that received placebo (1 to 2
      of 8 dogs), but this difference was not significant. CONCLUSIONS AND CLINICAL
      RELEVANCE: Short-term administration of clomipramine induced benign
      cardiovascular effects in dogs rather than the potentially dangerous arrhythmias
      or tachycardia reported following administration of tricyclic antidepressants to
      humans. Precautions regarding cardiovascular effects may not be needed for the
      use of clomipramine in healthy dogs.

PMID- 10951991
TI  - Pharmacokinetics of acetazolimide after intravenous and oral administration in
      horses.
AB  - OBJECTIVE: To determine the pharmacokinetics of acetazolamide administered IV and
      orally to horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Horses
      received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and
      blood samples were collected at regular intervals before and after
      administration. Samples were assayed for acetazolamide concentration by high
      performance liquid chromatography, and concentration-time data were analyzed.
      RESULTS: After IV administration of acetazolamide, data analysis revealed a
      median mean residence time of 1.71 +/- 0.90 hours and median total body clearance
      of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218
      ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/-
      1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours.
      Median oral bioavailability was 25 +/- 6%. CONCLUSIONS AND CLINICAL RELEVANCE:
      Oral pharmacokinetic disposition of acetazolamide in horses was characterized by
      rapid absorption, low bioavailability, and slower elimination than observed
      initially after IV administration. Pharmacokinetic data generated by this study
      should facilitate estimation of appropriate dosages for acetazolamide use in
      horses with hyperkalemic periodic paralysis.

PMID- 10951992
TI  - Effects of exercise intensity and duration on plasma beta-endorphin
      concentrations in horses.
AB  - OBJECTIVE: To determine the relationship between plasma beta-endorphin (EN)
      concentrations and exercise intensity and duration in horses. ANIMALS: 8 mares
      with a mean age of 6 years (range, 3 to 13 years) and mean body weight of 450 kg.
      PROCEDURE: Horses were exercised for 20 minutes at 60% of maximal oxygen
      consumption (VO2max) and to fatigue at 95% V02max. Plasma EN concentrations were
      determined before exercise, after a 10-minute warmup period, after 5, 10, 15, and
      20 minutes at 60% VO2max or at the point of fatigue (95% VO2max), and at regular
      intervals after exercise. Glucose concentrations were determined at the same
      times EN concentrations were measured. Plasma lactate concentration was measured
      5 minutes after exercise. RESULTS: Maximum EN values were recorded 0 to 45
      minutes after horses completed each test. Significant time and intensity effects
      on EN concentrations were detected. Concentrations were significantly higher
      following exercise at 95% VO2max, compared with those after 20 minutes of
      exercise at 60% VO2max (605.2 +/- 140.6 vs 312.3 +/- 53.1 pg/ml). Plasma EN
      concentration was not related to lactate concentration and was significantly but
      weakly correlated with glucose concentration for exercise at both intensities (r
      = 0.21 and 0.30 for 60 and 95% VO2max, respectively). CONCLUSIONS AND CLINICAL
      RELEVANCE: A critical exercise threshold exists for EN concentration in horses,
      which is 60% VO2max or less and is related to exercise intensity and duration.
      Even under conditions of controlled exercise there may be considerable
      differences in EN concentrations between horses. This makes the value of
      comparing horses on the basis of their EN concentration questionable.

PMID- 10951993
TI  - Additional kinematic variables to describe differences in the trot between
      clinically normal dogs and dogs with hip dysplasia.
AB  - OBJECTIVE: To describe the abnormal gait of dogs with hip dysplasia by use of
      kinematic gait analysis. ANIMALS: 19 large-breed dogs with moderate to severe
      clinical and radiographic evidence of hip dysplasia and 10 clinically normal dogs
      (controls). PROCEDURE: Kinematic and force plate data were collected, and degree
      of coxofemoral joint abduction-adduction, mediolateral foot movement, distance
      between hind feet, maximum hind foot elevation, mediolateral pelvic movement, and
      coxofemoral joint angular acceleration were calculated. Essential Fourier
      coefficients were determined and used to reconstruct mean angular acceleration
      curves. Fourier coefficients and foot and pelvic movement data were compared
      between groups. RESULTS: Dogs with hip dysplasia had a greater degree of
      coxofemoral joint adduction and range of abduction-adduction and greater lateral
      pelvic movement, compared with controls. Foot movement variables did not differ
      significantly between groups. Coxofemoral joint angular acceleration was greater
      in the middle to end of the stance phase, whereas deceleration was greater in the
      late stance to early swing phase and middle to end of the swing phase in dogs
      with hip dysplasia, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE:
      Differences in degree of coxofemoral joint abduction-adduction, amount of
      mediolateral pelvic movement, and coxofemoral joint angular acceleration between
      clinically normal dogs and dogs with hip dysplasia may indicate a compensation in
      gait of affected dogs as a result of discomfort or biomechanical effects
      attributable to hip dysplasia and degenerative joint disease. Information gained
      from kinematic and kinetic gait analyses may be useful in evaluating treatments
      for hip dysplasia in dogs.

PMID- 10951994
TI  - Use of an instrument sandwiched between the hoof and shoe to measure vertical
      ground reaction forces and three-dimensional acceleration at the walk, trot, and
      canter in horses.
AB  - OBJECTIVE: To develop an instrument that could be sandwiched between the hoof and
      shoe of horses and that would reliably measure vertical ground reaction forces
      and three-dimensional acceleration at the walk, trot, and canter. ANIMALS: 5
      clinically sound Thoroughbreds. PROCEDURES: The recording instrument (weight, 350
      g) consisted of 2 metal plates, 2 bolts, 4 load cells, and 3 accelerometers. It
      was mounted to the hoof with a glue-on shoe and devised to support as much load
      exerted by a limb as possible. The load cells and accelerometers were wired to a
      16-channel transmitter, and transmitted signals were received and amplified with
      a telemetry receiver. RESULTS: The recording instrument could measure in real
      time the 4 components of the ground reaction force or their resultant force along
      with acceleration in 3 dimensions as horses walked, trotted, or cantered on a
      treadmill. Patterns of force-time curves recorded for consecutive strides were
      similar to each other and to those previously reported, using a force plate.
      CONCLUSIONS AND CLINICAL RELEVANCE: The recording instrument developed for use in
      the present study allowed us to record vertical ground reaction force and
      acceleration in 3 dimensions in horses at the walk, trot, and canter.

PMID- 10951995
TI  - Effects of training on maximum oxygen consumption of ponies.
AB  - OBJECTIVES: To establish maximum oxygen consumption VO2max) in ponies of
      different body weights, characterize the effects of training of short duration on
      VO2max, and compare these effects to those of similarly trained Thoroughbreds.
      ANIMALS: 5 small ponies, 4 mid-sized ponies, and 6 Thoroughbreds. PROCEDURE: All
      horses were trained for 4 weeks. Horses were trained every other day for 10
      minutes on a 10% incline at a combination of speeds equated with 40, 60, 80, and
      100% of VO2max. At the beginning and end of the training program, each horse
      performed a standard incremental exercise test in which VO2max was determined.
      Cardiac output (Q), stroke volume (SV), and arteriovenous oxygen content
      difference (C [a-v] O2) were measured in the 2 groups of ponies but not in the
      Thoroughbreds. RESULTS: Prior to training, mean VO2max for each group was 82.6 =
      2.9, 97.4 +/- 13.2, and 130.6 +/- 10.4 ml/kg/min, respectively. Following
      training, mean VO2max increased to 92.3 +/- 6.0, 107.8 +/- 12.8, and 142.9 +/-
      10.7 ml/kg/min. Improvement in VO2max was significant in all 3 groups. For the 2
      groups of ponies, this improvement was mediated by an increase in Q; this
      variable was not measured in the Thoroughbreds. Body weight decreased
      significantly in the Thoroughbreds but not in the ponies. CONCLUSIONS AND
      CLINICAL RELEVANCE: Ponies have a lower VO2max than Thoroughbreds, and larger
      ponies have a greater VO2max than smaller ponies. Although mass-specific VO2max
      changed similarly in all groups, response to training may have differed between
      Thoroughbreds and ponies, because there were different effects on body weight.

PMID- 10951997
TI  - Molecular studies on isopenicillin N synthases.
AB  - The isopenicillin N synthases isolated thus far are related to oxidases from
      other microorganisms and plants. These enzymes maintain a non-heme monoferrous
      dependent catalytic centre comprising a HisXAsp(53-57)XHis motif and a crucial
      substrate-binding pocket with an ArgXSer motif for their functionality. The
      elucidation of these motifs was dependent on information collated from studies on
      structural chemistry, structural biology, site-directed engineered mutations and
      biochemical experiments. It is envisaged that these enzymes can potentially be
      improved through molecular breeding and protein engineering.

PMID- 10951996
TI  - Pharmacokinetics and tissue distribution of amoxicillin in healthy and Salmonella
      Typhimurium-inoculated pigs.
AB  - OBJECTIVE: To determine pharmacokinetics and tissue distribution of amoxicillin
      in healthy and Salmonella Typhimurium-inoculated pigs. ANIMALS: 12 healthy pigs
      and 12 S Typhimurium-inoculated pigs. PROCEDURE: Concentration of amoxicillin in
      tissue was measured by use of high-performance liquid chromatography 4, 8, 12,
      and 24 hours after IM administration. Pharmacokinetic values of amoxicillin in
      plasma were assessed by use of a 1-compartment model with first-order absorption.
      RESULTS: Inoculation caused diarrhea and increased rectal temperature and WBC
      count. Absorption half-life was shorter in inoculated pigs (0.26 hours) than in
      healthy pigs (0.71 hours), and inoculated pigs had longer elimination half-life.
      Distribution ratios in healthy pigs ranged from 0.31 to 0.56 and in inoculated
      pigs ranged from 0.14 to 0.48. Ratios for distribution to intestinal mucosa
      ranged from 0.34 to 1.16 in healthy pigs and from 0.22 to 0.36 in inoculated
      pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Salmonella Typhimurium inoculation
      altered absorption of amoxicillin from the injection site and prolonged
      elimination half-life. However, distribution of amoxicillin to intestinal tract
      tissue was only affected to a minor degree.

PMID- 10951998
TI  - Influence of the aeration rate on the yields of the biocontrol nematode
      Heterorhabditis megidis in monoxenic liquid cultures.
AB  - The entomopathogenic nematode-bacterium complex Heterorhabditis megidis
      Photorhabdus luminescens was cultured in 10-1 internal loop bioreactors with
      marine impellers at aeration rates of 0.3 vvm and 0.7 vvm. Process parameters
      like impeller velocity and oxygen saturation were controlled at equal set points.
      The bacterial density was assessed at 24 h. Nematode dauer juveniles (DJ) were
      then inoculated and the development to adults after 8 days and final DJ yields
      after 16 days were recorded. The bacterial population density and the nematode
      inoculum development was variable and was not influenced by the aeration rate. A
      significant effect on the yield was recorded at the highest aeration rate. This
      result was confirmed by a direct comparison in two 5-1 internal loop glass
      bioreactors at 0.3 vvm and 1.0 vvm, which were inoculated with nematode and
      bacterium pre-cultures from the same flask culture. Possible reasons for the
      positive correlation between aeration rate and DJ yield are discussed.

PMID- 10951999
TI  - Hydrodynamic aspects and Arthrospira growth in two outdoor tubular undulating row
      photobioreactors.
AB  - Two tubular undulating row photobioreactors (TURPs) with a very high illuminated
      surface/volume ratio (400 m(-1)) were designed and constructed for the growth of
      photosynthetic micro-organisms. Experiments were conducted under outdoor
      conditions; and Arthrospira recycling was performed with airlifts (one for each
      row). The rows in each reactor faced east-west and consisted of a flexible
      polyvinyl chloride pipe (22 m long, 0.01 m bore) arranged in a sinusoidal shape.
      We studied the hydraulic performance of the sine-shaped photobioreactor rows
      during culture recycling in the TURPs at a very high Reynolds number (4,200),
      when Arthrospira showed Newtonian fluid behavior. The sinusoidal pipe arrangement
      imposed a sine waveform on the culture, which led to better light utilization.
      During summer, a volumetric productivity of 2.2 g l(-1) day(-1) was reached in
      the TURP-5r (5 rows m(-2)), whereas an area productivity of 35 g m(-2) day(-1)
      was obtained in the TURP-10r (10 rows m(-2)). This was due to more light being
      available in the TURP-5r, because its rows were more spaced out and the photic
      ratio (Rf) was low (3.0). In the TURP-10r, the closer rows caused a dilution of
      the sunlight, but gave a better light distribution inside the Arthrospira culture
      and improved the light utilization. This was attributed to the high Rf (6.0) of
      this reactor.

PMID- 10952000
TI  - Batch and continuous cultivation of Anaerobiospirillum succiniciproducens for the
      production of succinic acid from whey.
AB  - Batch and continuous cultivation of Anaerobiospirillum succiniciproducens were
      systematically studied for the production of succinic acid from whey. Addition of
      2.5 g l(-1) yeast extract and 2.5 g l(-1) polypeptone per 10 g l(-1) whey was
      most effective for succinic acid production from both treated and nontreated
      whey. When 20 g l(-1) nontreated whey and 7 g l(-1) glucose were used as
      cosubstrates, the yield and productivity of succinic acid reached at the end of
      fermentation were 95% and 0.46 g (1 h)(-1), respectively. These values were
      higher than those obtained using nontreated whey alone [93% and 0.24 g (1 h)(-1)
      for 20 g l(-1) whey]. Continuous fermentation of A. succiniciproducens at an
      optimal dilution rate resulted in the production of succinic acid with high
      productivity [1.35 g (1 h)(-1)], high conversion yield (93%), and higher ratio of
      succinic acid to acetic acid (5.1:1) from nontreated whey.

PMID- 10952001
TI  - Characterisation of the shrinkage of calcium alginate gel membrane with
      immobilised Lactobacillus rhamnosus.
AB  - To quantify the shrinkage of calcium alginate gel membrane as a support matrix
      for immobilising cells during the fermentation of Lactobacillus rhamnosus,
      factors including time, pH, membrane thickness, and the concentrations of
      immobilised cells, lactic acid, glucose, and calcium chloride were examined by
      statistical experimental design. A Plackett-Burman design was used for the first
      screening experiment to identify the important factors which caused the divergent
      effects. Uniform Design, a powerful modelling design technique, was thus chosen
      to design the modelling experiments. Through a non-linear step-wise regression
      analysis, the predictive mathematical model of the shrinkage in membrane
      thickness was established and the significant main effects and two-factor
      interactions were identified. However, no significant model equations could be
      obtained for the shrinkage in area and volume of gel membranes. The methodology
      developed can be extrapolated to the quantitative characterisation of shrinkage
      in other immobilised gel matrices, which will be very useful in mathematical
      modelling, design, operation and scale-up of gel immobilised cell systems.

PMID- 10952002
TI  - Growth of Steptomyces hygroscopicus in rotating-wall bioreactor under simulated
      microgravity inhibits rapamycin production.
AB  - Growth of Streptomyces hygroscopicus under conditions of simulated microgravity
      in a rotating-wall bioreactor resulted in a pellet form of growth, lowered dry
      cell weight, and inhibition of rapamycin production. With the addition of Teflon
      beads to the bioreactor, growth became much less pelleted, dry cell weight
      increased but rapamycin production was still markedly inhibited. Growth under
      simulated microgravity favored extracellular production of rapamycin, in contrast
      to a greater percentage of cell-bound rapamycin observed under normal gravity
      conditions.

PMID- 10952003
TI  - In vitro synthesis of poly(3-hydroxydecanoate): purification and enzymatic
      characterization of type II polyhydroxyalkanoate synthases PhaC1 and PhaC2 from
      Pseudomonas aeruginosa.
AB  - For the first time, the purification has been achieved of the type II
      polyhydroxyalkanoate (PHA) synthases PhaC1 and PhaC2 from Pseudomonas aeruginosa
      applying N-terminal His6-tag fusions and metal chelate affinity chromatography.
      In vivo His6-tagged PHA synthase activity was confirmed by functional expression
      of the corresponding genes in Escherichia coli, and PHA synthase activity could
      also be measured in vitro with the enzymes. The specific enzyme activity of PHA
      synthases PhaC1 and PhaC2 was 0.039 U mg(-1) and 0.035 U mg(-1) protein,
      respectively. Kinetic studies showed a lag phase for both PHA synthases using
      (R,S)-3-hydroxydecanoyl-CoA as substrate. Specific enzyme activity was increased
      to 0.055 U mg(-1) when the phasin GA24 from Ralstonia eutropha was added to the
      assay. CoA inhibited PHA synthase activity, and a Ki of 85 microM was determined.
      A two-enzyme system was established, employing commercially available acyl-CoA
      synthetase and PHA synthase, which allowed the in vitro de novo PHA granule
      formation and the in vitro synthesis of poly(3-hydroxydecanoate) exhibiting a
      weight average molar mass of 9.8 x 10(4) g mol(-1), and which occurred
      independently of pre-existing PHA granules.

PMID- 10952004
TI  - Gene cloning and overproduction of low-specificity D-threonine aldolase from
      Alcaligenes xylosoxidans and its application for production of a key intermediate
      for parkinsonism drug.
AB  - The dtaAX gene encoding a pyridoxal 5'-phosphate (pyridoxal-P)-dependent low
      specificity D-threonine aldolase was cloned from the chromosomal DNA of
      Alcaligenes xylosoxidans IFO 12669. It contains an open reading frame consisting
      of 1,134 nucleotides corresponding to 377 amino acid residues. The predicted
      amino acid sequence displayed 54% identity with that of D-threonine aldolase from
      gram-positive bacteria Arthrobacter sp. DK-38, but showed no significant
      similarity with those of other known pyridoxal-P enzymes. This gram-negative
      bacterial enzyme was highly overproduced in recombinant Escherichia coli cells,
      and the specific activity of the enzyme in the cell extract was as high as 18
      U/mg (purified enzyme 38.6 U/mg), which was 6,000 times higher than that from the
      wild-type Alcaligenes cell extract. The recombinant enzyme was thus feasibly
      purified to homogeneity by ammonium sulfate fractionation and DEAE-Toyopearl
      chromatography steps. The recombinant low-specificity D-threonine aldolase was
      shown to be an efficient biocatalyst for resolution of L-beta-3,4
      methylenedioxyphenylserine, an intermediate for production of a therapeutic drug
      for Parkinson's disease.

PMID- 10952005
TI  - Expression in Escherichia coli, purification and kinetic analysis of the
      aspartokinase and aspartate semialdehyde dehydrogenase from the rifamycin SV
      producing Amycolatopsis mediterranei U32.
AB  - The operon encoding aspartokinase and aspartate semialdehyde dehydrogenase was
      cloned and sequenced from rifamycin-SV-producing Amycolatopsis mediterranei U32
      previously. In the present work, these two genes were introduced into the
      auxotrophic Escherichia coli strain CGSC5074 (ask-) and E. coli X6118 (asd-),
      respectively. The A. mediterranei U32 asparto-kinase and aspartate semialdehyde
      dehydrogenase genes can be functionally expressed in E. coli and the gene
      products are able to substitute for the E. coli enzymes. Histidine-tagged
      aspartokinase and aspartate semialdehyde dehydrogenase were partially purified
      from E. coli cellular extracts and their kinetic characteristics were studied.
      Both aspartokinase and aspartate semialdehyde dehydrogenase showed typical
      Michaelis-Menten type substrate saturation patterns. Aspartokinase has Km values
      of 3.4 mM for aspartate and 2.3 mM for ATP, while aspartate semialdehyde
      dehydrogenase has Km values of 1.25 mM for DL-aspartate semialdehyde and 0.73 mM
      for NADP, respectively. Aspartokinase was inhibited by L-threonine, L-lysine, and
      L-methionine, but not by L-isoleucine and diaminopimelate. Aspartate semialdehyde
      dehydrogenase was not inhibited by any of the end-product amino acids at a
      concentration of less than 5 mM. Hill plot analysis suggested that asparto-kinase
      was subject to allosteric control by L-threonine. Repression of both
      aspartokinase and aspartate semi-aldehyde dehydrogenase gene transcription in A.
      mediterranei U32 by L-lysine, L-methionine, L-threonine, and L-isoleucine were
      found. The network of regulation of aspartokinase and aspartate semialdehyde
      dehydrogenase in rifamycin SV-producing A. mediterranei U32 is presented.

PMID- 10952006
TI  - Molecular cloning and characterization of a gene encoding glutaminase from
      Aspergillus oryzae.
AB  - A glutaminase from Aspergillus oryzae was purified and its molecular weight was
      determined to be 82,091 by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry. Purified glutaminase catalysed the hydrolysis not only
      of L-glutamine but also of D-glutamine. Both the molecular weight and the
      substrate specificity of this glutaminase were different from those reported
      previously [Yano et al. (1998) J Ferment Technol 66: 137-143]. On the basis of
      its internal amino acid sequences, we have isolated and characterized the
      glutaminase gene (gtaA) from A. oryzae. The gtaA gene had an open reading frame
      coding for 690 amino acid residues, including a signal peptide of 20 amino acid
      residues and a mature protein of 670 amino acid residues. In the 5'-flanking
      region of the gene, there were three putative CreAp binding sequences and one
      putative AreAp binding sequence. The gtaA structural gene was introduced into A.
      oryzae NS4 and a marked increase in activity was detected in comparison with the
      control strain. The gtaA gene was also isolated from Aspergillus nidulans on the
      basis of the determined nucleotide sequence of the gtaA gene from A. oryzae.

PMID- 10952007
TI  - Overexpression of the lys1 gene in Penicillium chrysogenum: homocitrate synthase
      levels, alpha-aminoadipic acid pool and penicillin production.
AB  - Homocitrate synthase activity (encoded by the lys1 gene) catalyzes the first step
      of the lysine and penicillin pathway and is highly sensitive to feedback
      regulation by L-lysine. The transcript levels of the lys1 gene and the
      homocitrate synthase activity are high during the growth phase and decrease
      during the antibiotic production phase, except in the high penicillin producer
      strain AS-P-99 which maintained high levels of homocitrate synthase activity in
      cultures at 96 h and 120 h. The lys1 gene was overexpressed in Penicillium
      chrysogenum using additional copies of lys1 with its own promoter or under the
      control of the pcbC promoter in either autonomously replicating or integrative
      vectors. Transformants containing 3 to 32 additional copies of the lys1 gene were
      selected. Some of these transformants, particularly Ti-C4 (integrative) and TAR
      L9 (with autonomously replicating plasmids) showed very high levels of lys1
      transcript and, in the case of TAR-L9, high levels of homocitrate synthase
      activity in cultures of 120 h. However, these transformants did not show
      increased alpha-aminoadipate or lysine pools. A mutant P. chrysogenum L-G-
      disrupted in the lys2 gene (therefore lacking the lysine branch of the pathway)
      showed increased alpha-aminoadipate levels and produced higher levels of
      penicillin than non-disrupted control strains. Overexpression of the lys1 gene in
      the L-G- mutant resulted in high homocitrate synthase levels but no additional
      increase of the alpha-aminoadipate pool or penicillin production levels. These
      results suggest that after amplification of the homocitrate synthase levels there
      are other limiting steps in the common stem of the lysine and penicillin
      pathways.

PMID- 10952008
TI  - A green fluorescent protein fusion strategy for monitoring the expression,
      cellular location, and separation of biologically active organophosphorus
      hydrolase.
AB  - Organophosphorus hydrolase (OPH) is capable of degrading a variety of pesticides
      and nerve agents. We have developed a versatile monitoring technique for
      detecting the amount of OPH during the expression and purification steps. This
      involves fusion of the gene for green fluorescent protein (GFP) to the 5' end of
      the OPH gene and subsequent expression in Escherichia coli. The synthesized
      fusion protein was directly visualized due to the optical properties of GFP.
      Western blot analyses showed that the correct fusion protein was expressed after
      IPTG-induction. Also, the in vivo GFP fluorescence intensity was proportional to
      the OPH enzyme activity. Moreover, the OPH, which forms a dimer in its active
      state, retained activity while fused to GFP. Enterokinase digestion experiments
      showed that OPH was separated from the GFP reporter after purification via
      immobilized metal affinity chromatography, which in turn was monitored by
      fluorescence. The strategy of linking GFP to OPH has enormous potential for
      improving enzyme production efficiency, as well as enhancing field use, as it can
      be monitored at low concentrations with inexpensive instrumentation based on
      detecting green fluorescence.

PMID- 10952009
TI  - Molecular design of novel metal-binding oligomeric human metallothioneins.
AB  - Genes for dimeric and tetrameric human metallothionein (hMT) were designed and
      successfully overexpressed in Escherichia coli to generate functional oligomeric
      hMTs. An hMT synthesized with prokaryotic codons, a linker encoding a gly-gly-gly
      tripeptide, and Met-deficient hMT-II was ligated to create a dimeric hMT, from
      which a tetrameric hMT was then constructed. The increased molecular size of the
      constructs resulted in improved stability and productivity in E. coli. The
      oligomeric proteins formed inclusion bodies which were dissolved with
      dithiothreitol, and the purified apometallothioneins were reconstituted with Cd
      or Zn ions in a reducing condition. The oligomeric hMT proteins incubated with Cd
      ions showed a typical Cd-thiolate absorbance peak at 245-255 nm. The dimeric and
      tetrameric hMT proteins exhibited both Cd and Zn binding activities that were
      respectively two and four times higher than those of the hMT-II monomer protein.
      These novel oligomeric hMTs may be useful in bioremediation for heavy metals.

PMID- 10952010
TI  - Construction of an engineered yeast with glucose-inducible emission of green
      fluorescence from the cell surface.
AB  - An engineered yeast with emission of fluorescence from the cell surface was
      constructed. Cell surface engineering was applied to display a visible reporter
      molecule, green fluorescent protein (GFP). A glucose-inducible promoter GAPDH as
      a model promoter was selected to control the expression of the reporter gene in
      response to environmental changes. The GFP gene was fused with the gene encoding
      the C-terminal half of alpha-agglutinin of Saccharomyces cerevisiae having a
      glycosylphosphatidylinositol anchor attachment signal sequence. A secretion
      signal sequence of the fungal glucoamylase precursor protein was connected to the
      N-terminal of GFP. This designed gene was integrated into the TRP1 locus of the
      chromosome of S. cerevisiae with homologous recombination. Fluorescence
      microscopy demonstrated that the transformant cells emitted green fluorescence
      derived from functionally expressed GFP involved in the fusion molecule. The
      surface display of GFP was further verified by immunofluorescence labeling with a
      polyclonal antibody (raised in rabbits) against GFP as the first antibody and
      Rhodamine Red-X-conjugated goat anti-rabbit IgG as the second antibody which
      cannot penetrate into the cell membrane. The display of GFP on the cell surface
      was confirmed using a confocal laser scanning microscope and by measuring
      fluorescence in each cell fraction obtained after the subcellular fractionation.
      As GFP was proved to be displayed as an active form on the cell surface,
      selection of promoters will endow yeast cells with abilities to respond to
      changes in environmental conditions, including nutrient concentrations in the
      media, through the emission of fluorescence.

PMID- 10952011
TI  - Construction of a flocculent brewer's yeast strain secreting Aspergillus niger
      beta-galactosidase.
AB  - One way of improving heterologous protein production is to use high cell density
      systems, one of the most attractive being the flocculating yeast production
      system. Also, lactose is available in large amounts as a waste product from
      cheese production processes. The construction of flocculent and non-flocculent
      brewer's yeast strains secreting beta-galactosidase and growing on lactose is
      presented. A plasmid was constructed coding for an extracellular beta
      galactosidase of Aspergillus niger and having, as selective marker, the yeast
      CUP1 gene conferring resistance to copper. This selective marker allows for the
      transformation of wild-type yeasts. This work represents an important step
      towards the study of heterologous protein secretion by flocculent cells.

PMID- 10952012
TI  - Polymerization of guaiacol by lignin-degrading manganese peroxidase from
      Bjerkandera adusta in aqueous organic solvents.
AB  - Lignin-degrading manganese (II) peroxidase (MnP) purified from the culture of a
      wood-rotting basidiomycete, Bjerkandera adusta, was used in the polymerization of
      guaiacol. MnP was found to catalyze polymerization of guaiacol in 50% aqueous
      acetone, dimethyl formamide, methanol, ethanol, dioxane, acetonitrile, ethylene
      glycol and methylcellosolve. Maximum yield of polyguaiacol was achieved in 50%
      aqueous acetone. The weight average molecular weight (Mw) of the polymer was
      estimated to be 30,300 by gel permeation chromatography. However, matrix-assisted
      laser desorption ionization time of flight mass spectroscopy (MALDI-TOF-MS)
      analysis gave a more reliable Mw of 1,690. IR, 13C-NMR, MALDI-TOF-MS and
      pyrolysis GC-MS analyses showed the presence of C-C and C-O linkages and quinone
      structure in polyguaiacol. It was also indicated that polyguaiacol has a methoxy
      phenyl group as the terminal moiety. This suggests that polyguaiacol is a
      branched polymer in which guaiacol units are cross-linked at the phenolic group.
      Thermal gravimetric and differential scanning calorimetric analyses were also
      carried out. MnP also catalyzed the polymerization of o-cresol, 2,6
      dimethoxyphenol and other phenolic compounds and aromatic amines. Mw of these
      polymers ranged from around 1,000 to 1,500.

PMID- 10952013
TI  - Limited feeding of potassium nitrate for intracellular lipid and triglyceride
      accumulation of Nannochloris sp. UTEX LB1999.
AB  - Limited feeding of nitrate during culture of Nannochloris sp. UTEX LB1999 for
      intracellular lipid and triglyceride accumulation was investigated with the aim
      of obtaining cells superior for liquefaction into a fuel oil. The intracellular
      lipid contents and the percentage of triglycerides in the lipids of cells grown
      in a nitrogen-limited medium (0.9 mM KNO3) were 1.3 times as high as those grown
      in a modified NORO medium containing 2.0-9.9 mM KNO3. However, the cell
      concentration was too low for the practical production of fuel oil by high
      pressure liquefaction of the cell mass. A single feeding of 0.9 mM nitrate after
      nitrate depletion during cultivation in a nitrate-limited medium increased the
      cell concentration to twice that obtained without such feeding, and the lipid
      content was maintained at a high level. The timing of nitrate feeding, i.e.,
      whether it was given during the log phase (before nitrate depletion), the
      constant growth phase (just after the depletion), or the stationary phase (after
      the depletion), had negligible effect on the intracellular lipid content and
      percentage of triglycerides in the lipids. When 0.9 mM nitrate was intermittently
      fed ten times during the log phase in addition to the initial nitrate feed (0.9
      mM), the cell concentration reached almost the same (2.16 g/l) and the
      intracellular lipid content and the percentage of triglycerides in the lipids
      increased from 31.0 to 50.9% and 26.0 to 47.6%, respectively, compared with those
      of cells cultured in a modified NORO medium containing 9.9 mM KNO3 without
      additional nitrate feeding.

PMID- 10952014
TI  - The effect of heat-shocking on batch fermentation by Clostridium beijerinckii
      NRRL B592.
AB  - In spite of the large-scale industrial use of the acetone-butanol fermentation
      process earlier this century (until 1983 in South Africa), very little has been
      published on the inoculum preparation techniques required for successful
      fermentation using these bacteria. In particular, heat-shocking has often been
      referred to as "useful" but no quantitative data are available. Data presented in
      this paper demonstrate and quantify the effect of heat-shocking on batch
      fermentation yields using one organism capable of this fermentation.

PMID- 10952016
TI  - Competition between n-alkane-assimilating yeasts and bacteria during colonization
      of sandy soil microcosms.
AB  - An n-alkane-assimilating strain of Candida tropicalis was selected in sandy soil
      inoculated with microorganisms from contaminated sites. Competition experiments
      with n-alkane utilizers from different strain collections confirmed that yeasts
      overgrow bacteria in sandy soil. Acidification of the soil is one of the
      colonization factors useful for the yeasts. It can be counteracted by addition of
      bentonite, a clay mineral with high ion exchange capacity, but not, however, by
      kaolin. Strains of different yeast species showed different levels of
      competitiveness. Strains of Arxula adeninivorans, Candida maltosa, and Yarrowia
      lipolytica overgrew strains of C. tropicalis, C. shehatae or Pichia stipitis. Two
      strains of C. maltosa and Y. lipolytica coexisted during several serial transfers
      under microcosm conditions.

PMID- 10952015
TI  - Biodegradability of volatile hydrocarbons of gasoline.
AB  - The biodegradability under aerobic conditions of volatile hydrocarbons (4-6
      carbons) contained in gasoline and consisting of n-alkanes, iso-alkanes,
      cycloalkanes and alkenes, was investigated. Activated sludge was used as the
      reference microflora. The biodegradation test involved the degradation of the
      volatile fraction of gasoline in closed flasks under optimal conditions. The
      kinetics of biodegradation was monitored by CO2 production. Final degradation was
      determined by gas chromatographic analysis of all measurable hydrocarbons (12
      compounds) in the mixture after sampling the headspace of the flasks. The
      degradation of individual hydrocarbons was also studied with the same
      methodology. When incubated individually, all hydrocarbons used as carbon
      sources, except 2,2-dimethylbutane and 2,3-dimethylbutane, were completely
      consumed in 30 days or less with different velocities and initial lag periods.
      When incubated together as constituents of the light gasoline fraction, all
      hydrocarbons were metabolised, often with higher velocities than for individual
      compounds. Cometabolism was involved in the degradation of dimethyl isoalkanes.

PMID- 10952017
TI  - Toluene degradation in the recycle liquid of biotrickling filters for air
      pollution control.
AB  - Pollutant degradation in biotrickling filters for waste air treatment is
      generally thought to occur only in the biofilm. In two experiments with toluene
      degrading biotrickling filters, we show that suspended microorganisms in the
      recycle liquid may substantially contribute to the overall pollutant removal. Two
      days after reactor start up, the overall toluene elimination capacity reached a
      maximum of 125 g m(-3) h(-1), which was twice that found during prolonged
      operation. High biodegradation activity in the recycle liquid fully accounted for
      this short-term peak of pollutant elimination. During steady-state operation, the
      toluene degradation in the recycle liquid was 21% of the overall elimination
      capacity, although the amount of suspended biomass was only 1% of the amount of
      immobilized biomass. The results suggest that biotrickling filter performance may
      be improved by selecting operating conditions allowing for the development of an
      actively growing suspended culture.

PMID- 10952018
TI  - Inducible nitric oxide synthase and inflammatory diseases.

PMID- 10952019
TI  - A repression-derepression mechanism regulating the transcription of human
      immunodeficiency virus type 1 in primary T cells.
AB  - BACKGROUND: Despite some controversy regarding the preferential infection and
      replication of human immunodeficiency virus type 1 (HIV-1), it appears that
      primary T lymphocytes, in their quiescent state, are nonpermissive for viral
      expression and propagation. Massive activation of viral gene expression occurs
      only when the host lymphocyte is activated. These observations prompted us to
      investigate the transcriptional regulation of HIV-1 in resting or activated T
      cells that were isolated from cord blood or adult peripheral blood. MATERIALS AND
      METHODS: To this end, we employed cellular purification and phenotyping
      techniques, in vitro protein-DNA binding studies, functional transactivation
      assays using proteins isolated from cord blood or adult peripheral blood T
      lymphocytes, and transfection experiments in primary T cells. RESULTS: We showed
      that transcription from the HIV-1 long terminal repeat is repressed in resting
      naive T lymphocytes; whereas, mitogenically stimulated CD4+ cells form an
      activator that derepresses transcription. Negative and positive regulation act
      through a repressor-activator target sequence (RATS), which shares homology with
      the interleukin-2 (IL-2) purine-rich response element, through the adjacent
      binding site of the nuclear factor of activated T cells (NFAT), and weakly,
      through the KB region. CONCLUSIONS: This regulation exerted by cellular
      transcription factors can account for several important features of HIV-1
      expression in primary CD4+ cells. Tight repression in resting naive T helper
      cells may be a main cause of viral latency and transcriptional activation
      accounts for massive viral production in activated T lymphocytes.

PMID- 10952020
TI  - Induction of placental heme oxygenase-1 is protective against TNFalpha-induced
      cytotoxicity and promotes vessel relaxation.
AB  - BACKGROUND: Pregnancy is characterized by an inflammatory-like process and this
      may be exacerbated in preeclampsia. The heme oxygenase (HO) enzymes generate
      carbon monoxide (CO) that induces blood vessel relaxation and biliverdin that
      acts as an endogenous antioxidant. MATERIALS AND METHODS: We examined the
      expression and localization of HO-1 and HO-2 in normal and preeclamptic placenta
      using reverse transcription polymerase chain reaction (RT-PCR), RNase protection
      assay, immunoblotting and immunohistochemistry. In addition, the effect of HO
      activation on tumor necrosis factor-alpha (TNFalpha) induced placental damage and
      on feto-placental circulation was studied. RESULTS: We provide the first evidence
      for the role of HO as an endogenous placental factor involved with cytoprotection
      and placental blood vessel relaxation. HO-1 was significantly higher at term,
      compared with first trimester placentae indicating its role in placental vascular
      development and regulation. HO-1 predominantly localized in the extravascular
      connective tissue that forms the perivascular contractile sheath around the
      developing blood vessels. HO-2 was localized in the capillaries, as well as the
      villous stroma, with weak staining of trophoblast. Induction of HO-1 caused a
      significant attenuation of TNFalpha-mediated cellular damage in placental villous
      explants, as assessed by lactate dehydrogenase leakage (p < 0.01). HO-1 protein
      was significantly reduced in placentae from pregnancies complicated with
      preeclampsia, compared with gestationally matched normal pregnancies. This
      suggests that the impairment of HO-1 activation may compromise the compensatory
      mechanism and predispose the placenta to cellular injury and subsequent maternal
      endothelial cell activation. Isometric contractility studies showed that hemin
      reduced vascular tension by 61% in U46619-preconstricted placental arteries.
      Hemin-induced vessel relaxation and CO production was inhibited by HO inhibitor,
      tin protoporphyrin IX. CONCLUSIONS: Our findings establish HO-1 as an endogenous
      system that offers protection against cytotoxic damage in the placenta,
      identifies the HO-CO pathway to regulate feto-placental circulation and provides
      a new approach to study the disease of preeclampsia.

PMID- 10952021
TI  - Motor neuron cell death in wobbler mutant mice follows overexpression of the G
      protein-coupled, protease-activated receptor for thrombin.
AB  - BACKGROUND: Mechanisms underlying neurodegeneration are actively sought for new
      therapeutic strategies. Transgenic, knockout and genetic mouse models greatly aid
      our understanding of the mechanisms for neuronal cell death. A naturally
      occurring, autosomal recessive mutant, known as wobbler, and mice transgenic for
      familial amyotrophic lateral sclerosis (FALS) superoxide dismutase (SOD)1
      mutations are available, but the molecular mechanisms remain equally unknown.
      Both phenotypes are detectable after birth. Wobbler is detectable in the third
      week of life, when homozygotes (wr/wr) exhibit prominent gliosis and significant
      motor neuron loss in the cervical, but not in lumbar, spinal cord segments. To
      address molecular mechanisms, we evaluated "death signals" associated with the
      multifunctional serine protease, thrombin, which leads to apoptotic motor
      neuronal cell death in culture by cleavage of a G-protein coupled, protease
      activated receptor 1 (PAR-1). MATERIALS AND METHODS: Thrombin activities were
      determined with chromogenic substrate assays, Western immunoblots and
      immunohistochemistry were performed with anti-PAR-1 to observe localizations of
      the receptor and anti-GFAP staining was used to monitor astrocytosis. PAR-1 mRNA
      levels and locations were determined by reverse transcription polymerase chain
      reaction (qRT-PCR) and in situ hybridizations. Cell death was monitored with in
      situ DNA fragmentation assays. RESULTS: In preliminary studies we found a 5-fold
      increase in PAR-1 mRNA in cervical spinal cords from wr/wr, compared with wild
      type (wt) littermates. Our current studies suggested that reactive astrocytosis
      and motor neuron cell death were causally linked with alterations in thrombin
      signaling. PAR-1 protein expression was increased, as demonstrated by
      immunocytochemistry and confirmed with in situ hybridization, in phenotypic wr/wr
      motor neurons, compared with wt, but not in astrocytes. This increase was much
      greater in cervical, compared with lumbar, segments, paralleling motor neuron
      degeneration. We also found, using reverse transcription polymerase chain
      reaction (qRT-PCR) with RNA from genotyped embryos, that PAR-1 was already
      increased in wr/wr cords at E12, the earliest time examined. CONCLUSIONS: Thus,
      motor neuron degeneration and death follows PAR-1 expression both temporally and
      topographically in wobbler mice. Since our culture studies show that thrombin
      mobilized [Ca2+]i by activating PAR-1, eventually leading to motor neuron
      apoptosis, up-regulation of PAR-1 during development may contribute both to
      "appropriate" as well as "inappropriate" neuronal death in wobbler.

PMID- 10952022
TI  - Elevated A beta and apolipoprotein E in A betaPP transgenic mice and its
      relationship to amyloid accumulation in Alzheimer's disease.
AB  - BACKGROUND: Amyloid-beta (A beta) accumulates in plaques and as cerebral amyloid
      angiopathy (CAA) in the brains of both Alzheimer's disease (AD) patients and
      transgenic A betaPPswe/tg2576 (tg2576) mice. Increasingly, evidence in humans and
      mice shows this process to be modulated by apolipoprotein E (apoE). MATERIALS AND
      METHODS: To explore this relationship, we measured apoE and A beta levels in
      brains of tg2576 mice and controls at intervals between 2 and 20 months. In
      addition, A beta concentrations in plasma and muscle of these animals were also
      quantified. RESULTS: Quite strikingly, we found that the amount of tg2576 mice
      brain apoE was elevated by an average of 45%, relative to the control mice from 2
      months on. The level of brain apoE soared after 14 months to almost 60% greater
      than the level found in control mice. A beta concentrations in brains before 9
      months were less than 2 ng/mg of protein, but by 14 months concentrations rose to
      8.7 ng/mg, and by 20 months to 47 ng/mg. In plasma, we noted that the levels of A
      beta in tg2576 mice declined from above 30 ng/ml prior to 12 months to 14 ng/ml
      by 14 months. Histology showed that A beta plaques and CAA began to be
      discernible in the tg2576 mice at about 9 and 20 months of age, respectively.
      CONCLUSIONS: ApoE was immunocytochemically detected in neuritic plaques that were
      positive for thioflavine-S. We suggest that the elevation of brain apoE in tg2576
      mice participates in an age-related dysregulation of A beta clearance and signals
      the start of A beta sequestration during the time of cognitive dysfunction.

PMID- 10952023
TI  - Molecular expression analysis of restrictive receptor for interleukin 13, a brain
      tumor-associated cancer/testis antigen.
AB  - BACKGROUND: The vast majority of patients with high-grade gliomas (HGG) over
      express interleukin 4 (IL4)-independent binding sites for IL13 in situ. In
      addition, mutated IL13-based cytotoxins directed specifically toward glioma
      associated sites are arguably the most active anti-glioma agents. Two IL13
      receptor (R) proteins were identified: (1) IL13R alpha', a component of the
      signaling, heterodimeric high-affinity receptor for IL13 that is shared with IL4,
      and (2) IL13R alpha, a monomeric, IL4-independent receptor. MATERIALS AND
      METHODS: We analyzed gene expression of IL13R alpha, IL13R alpha' and that of
      IL4Rbeta, which is the other subunit of the shared IL13/4 receptor. The study was
      conducted with 40 human normal adult tissues, 20 discrete regions of the central
      nervous system (CNS), 7 fetal tissues, several cultured cell lines, and surgical
      CNS specimens. RESULTS: The most striking feature of the IL13R alpha gene
      expression was the virtual lack of its transcripts within the CNS. Furthermore,
      only the testes exhibited a prominent presence of the mRNA for IL13R alpha among
      peripheral organs. In contrast, the components of the shared IL13/4 receptor were
      readily detected both in the CNS and in vital organs, such as liver, heart,
      lungs, and gastrointestinal tract. CONCLUSIONS: The results strongly support a
      need to redirect IL13 towards its more restrictive, IL4-independent, receptor for
      glioma diagnosis and therapies. Moreover, the gene for IL13R alpha resides on
      chromosome X. Since IL13R alpha is (1) a cancer-associated protein, (2) virtually
      restricted to testes among normal tissues, and (3) its gene is on chromosome X,
      IL13R alpha is unexpectedly categorized as a cancer/testis antigen. Our findings
      make IL13R alpha even more attractive as a target for variety of approaches in
      glioma molecular management.

PMID- 10952024
TI  - A functional proteomics screen of proteases in colorectal carcinoma.
AB  - BACKGROUND: Proteases facilitate several steps in cancer progression. To identify
      proteases most suitable for drug targeting, actual enzyme activity and not
      messenger RNA levels or immunoassay of protein is the ideal assay readout.
      MATERIALS AND METHODS: An automated microtiter plate assay format was modified to
      allow detection of all four major classes of proteases in tissue samples. Fifteen
      sets of colorectal carcinoma biopsies representing primary tumor, adjacent normal
      colon, and liver metastases were screened for protease activity. RESULTS: The
      major proteases detected were matrix metalloproteases (MMP9, MMP2, and MMP1),
      cathepsin B, cathepsin D, and the mast cell serine proteases, tryptase and
      chymase. Matrix metalloproteases were expressed at higher levels in the primary
      tumor than in adjacent normal tissue. The mast cell proteases, in contrast, were
      at very high levels in adjacent normal tissue, and not detectable in the
      metastases. Cathepsin B activity was significantly higher in the primary tumor,
      and highest in the metastases. The major proteases detected by activity assays
      were then localized in biopsy sections by immunohistochemistry. Mast cell
      proteases were abundant in adjacent normal tissue, because of infiltration of the
      lamina propria by mast cells. Matrix metalloproteases were localized to the tumor
      cells themselves; whereas, cathepsin B was predominantly expressed by macrophages
      at the leading edge of invading tumors. Although only low levels of urinary
      plasminogen activator were detected by direct enzyme assay, immunohistochemistry
      showed abundant protein within the tumor. CONCLUSIONS: This analysis, surveying
      all major classes of proteases by assays of activity rather than
      immunolocalization or in situ hybridization alone, serves to identify proteases
      whose activity is not completely balanced by endogenous inhibitors and which may
      be essential for tumor progression. These proteases are logical targets for
      initial efforts to produce low molecular weight protease inhibitors as potential
      chemotherapy.

PMID- 10952025
TI  - Regulatory effect of cytokine production in patients with cerebral infarction by
      Yulda-Hanso-Tang.
AB  - Yulda-Hanso-Tang (YH-Tang) is a prescription for the Taeumin cerebral infarction
      (CI) patients according to Sasang constitution philosophy. Taeumin patients with
      CI were treated with YH-Tang during the acute stage. Clinical signs of CI
      disappeared markedly in about 2 weeks after oral administration of YH-Tang in all
      patients. The mean interleukin (IL)-2 serum levels were lower in the patients
      with CI than in the normal groups, whereas the mean IL-4, IL-6 and IgE levels
      were significantly higher in the patients. There were no significant differences
      in interferon-gamma (IFN-gamma) levels between the groups. Serum IFN-gamma and IL
      2 levels derived from T helper (Th)1 cells elevated significantly in the patients
      with CI by YH-Tang administration. Significant reduced serum levels of IL-4 and
      IL-6 derived from Th2 cells and IgE were observed in the patients treated with YH
      Tang. During the period of YH-Tang administration, there were no other adverse
      effects. The data indicate that YH-Tang has a good CI treatment effect, and that
      its action may be due to regulation of cytokine production.

PMID- 10952026
TI  - In vitro treatment with interleukin-2 normalizes type-1 cytokine production by
      lymphocytes from elderly.
AB  - The term immunosenescence is taken to mean the deterioration of immune function
      seen in elderly, which is manifested in increased susceptibility to infectious
      diseases, neoplasias, and autoimmune diseases. It is only recently that we have
      begun to understand the cellular and molecular changes involved. Of special
      interest in this regard are observations of a decline in synthesis of Type-1
      cytokines which predisposes to diminished cell mediated immunity. We have
      evaluated the production of type 1 cytokines in old and young donors either in
      presence or in absence of recombinant interleukin-2 (rIL-2). Lymphocytes were
      stimulated with plastic bound anti-CD3 and after 48 h the supernatants were
      harvested and stored at -70 degrees C until assay. Type 1 cytokine, i.e. IL-12
      and interferon-gamma (IFN-gamma) production by anti-CD3 stimulated lymphocytes
      from old subjects was significantly reduced when compared to that from young
      ones. This impaired production was reversed by adding rIL-2 in the culture
      medium. In previous studies on aged subjects, we have been able to demonstrate
      that in vitro treatment with rIL-2 completely restores proliferative responses
      and partially rescues the increased apoptosis of T cell cultures. Present and
      previous results suggest that rIL-2 completely restores Type 1 responses by
      overcoming the well known costimulation deficit of aged lymphocytes.

PMID- 10952027
TI  - Serum regulates the expression of complement receptor 2 on human B cell lines.
AB  - Complement receptor 2 (CR2) participates in the regulation of B cell responses to
      antigen. In this study we report that treatment of IM-9 B lymphoblastoid cells or
      Raji Burkitt's lymphoma cells with 10% heat-inactivated fetal bovine serum for 24
      hr increased both the CR2 mRNA level and CR2 surface protein expression more than
      two-fold. No change in the CR2 expression level was observed if cells were
      cultured in serum-free medium. The CD19 mRNA level decreased after 24 hr
      independently of the presence of serum. The serum-stimulated increase in CR2
      expression was not due to changes in the proliferative capacity of the cells and
      could not be mimicked by various cytokines. However, IFN-gamma as well as OKB7, a
      CR2-specific monoclonal antibody, blocked the serum-induced increase in CR2
      expression at the mRNA level. Our data show for the first time that factors in
      serum induce the expression of the CR2 gene and that signals initiated by IFN
      gamma and OKB7 interfere with the serum-induced changes. Because stimuli that
      alter CR2 expression can influence the extent of the B cell response to antigen
      C3d complexes, serum factors may play a role in regulating the responsiveness of
      B cells.

PMID- 10952028
TI  - PSK and OK-432-induced immunomodulation of inducible nitric oxide (NO) synthase
      gene expression in mouse peritoneal polymorphonuclear leukocytes and NO-mediated
      cytotoxicity.
AB  - We investigated whether PSK (a polysaccharide from the mycelia of Coriolus
      versicolor) or OK-432 (a streptococcal preparation) can up-regulate inducible
      nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in
      mouse peritoneal polymorphonuclear leukocytes (PMNs). Six hrs after
      intraperitoneal injection of mice with PSK (2,500 microg/mouse) or OK-432 (100
      microg/mouse), mouse peritoneal PMNs were restimulated with PSK (500 microg/ml)
      or OK-432 (10 microg/ml) plus 100 U/ml of mouse interferon-gamma (IFN-gamma) in
      vitro. Northern blot analysis showed strong synergism between both PSK and OK-432
      and IFN-gamma for the induction of iNOS gene expression. NO production by PMNs
      was increased up to 20 microM (2 microM/10(6) PMNs/24 hrs) as measured by the
      Griess reagent method when PMNs were restimulated with PSK or OK-432 plus IFN
      gamma for 24 hrs, although tumor cell killing was not detected. NO concentrations
      of more than 80 microM were required for P815 tumor cell killing. These results
      suggest that PMNs produce NO after stimulation with PSK or OK-432 in combination
      with IFN-gamma and may regulate the immune system in vivo, although the NO
      production induced by these agents is insufficient for tumor cell killing in
      vitro.

PMID- 10952029
TI  - Heat shock treatment protects human HL-60 cells from apoptosis induced by lectin
      II isolated from Korean mistletoe, Visum album var. Coloratum.
AB  - Mistletoe lectin II (ML II) isolated from Korean mistletoe (Viscum album var.
      Coloratum), an effective therapeutic agent for cancers, is known to induce cell
      death via apoptosis. In the present study, we found the protective effect of heat
      shock treatment of human leukemia HL-60 cells against ML II-induced apoptosis.
      Exposure of HL-60 cells to ML II for 4 h resulted in apoptosis of the cells,
      which was evaluated by examining "DNA ladder" formation and DNA fragmentation
      assay. The DNA fragmentation was significantly reduced in the cells subjected to
      heat shock treatment by incubation at 42 degrees C for 1 h and subsequently
      allowed to recover for 2-16 h at 37 degrees C, prior to exposure to ML II. HL-60
      cells transfected with heat shock protein (hsp) 70 gene exhibited resistance to
      ML II-induced apoptosis very similar to that seen when untransfected cells were
      heat-shocked. These results indicate that ML II-induced apoptosis in HL-60 cells
      is inhibited by heat shock treatment, at least in part, via a hsp 70-mediated
      mechanism.

PMID- 10952030
TI  - Inhibitory effect of mast cell-mediated immediate-type allergic reactions by
      sulfapyridine.
AB  - We examined the effect of sulfapyridine on mast cell-mediated immediate-type
      allergic reactions. Sulfapyridine (1 and 10 microg/kg) significantly inhibited
      systemic allergic reaction induced by compound 48/80 in rats. Sulfapyridine (1
      and 10 microg/kg) also inhibited significantly local mast cell-mediated immediate
      type allergic reactions activated by anti-dinitrophenyl (DNP) IgE. Moreover,
      sulfapyridine inhibited histamine release dose-dependently in the rat peritoneal
      mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. When sulfapyridine
      was added, the level of cAMP in RPMC, transiently and significantly increased
      about 4-fold compared with that of basal cells. These results indicate that
      sulfapyridine inhibits mast cell-mediated immediate-type allergic reactions in
      vivo and in vitro.

PMID- 10952031
TI  - Suppression of immunoglobulin E-mediated anaphylactic reaction by Alpinia
      oxyphylla in rats.
AB  - We investigated the effect of Alpinia oxyphylla water extract (AOWE) on
      immunoglobulin E (IgE)-mediated anaphylaxis activated by anti-dinitrophenyl (DNP)
      IgE antibody. AOWE dose-dependently suppressed passive cutaneous anaphylaxis
      (PCA) when intraperitoneally or orally administered. On the other hand, it showed
      weak suppressive activity when administered intravenously. AOWE dose-dependently
      suppressed anaphylactic histamine release from rat peritoneal mast cells (RPMC)
      activated by anti-DNP IgE antibody. However, AOWE had a significant augmenting
      effect on anti-DNP IgE antibody-induced tumor necrosis factor-alpha secretion
      from RPMC. These results indicated that AOWE may possess strong antianaphylactic
      action and also suggest that differential activity following administration
      routes may be caused by difference of bioavailability.

PMID- 10952032
TI  - Protein kinase A or C modulates the apoptosis induced by lectin II isolated from
      Korean mistletoe, Viscum album var. Coloratum, in the human leukemic HL-60 cells.
AB  - Mistletoe lectins (MLs) are increasingly used as an anticancer drug in the
      treatment of human tumors. The cytotoxic activity of MLs against tumor cells is
      due to programmed cell death (apoptosis). The up- or down-regulation of protein
      kinase A (PKA) or C (PKC) is known to be associated with the regulation of drug
      induced apoptosis. Previously, we isolated cytotoxic MLII from the extract of
      Korean mistletoe (Viscum album var. Coloratum) and characterized its biochemical
      properties. The present study was designed to investigate the role of PKA and PKC
      in MLII-induced apoptosis. Exposure of human leukemia HL-60 cells to various
      doses of MLII resulted in apoptosis. However, the treatment of these cells with
      dibutyl-cyclic AMP (DB-cAMP), PKA activator, or 12-O-tertadecanoyl phorbol 13
      acetate (TPA), PKC activator, suppressed MLII-induced apoptosis. Furthermore,
      KT5720 and staurospoline, PKA and PKC inhibitors, respectively, reversed the
      suppression by DB-cAMP and TPA in the MLII-induced apoptosis of HL-60 cells.
      These results suggest that the activation of PKA or PKC was involved in the
      suppression of MLII-induced apoptosis in HL-60 cells. Collectively, these results
      indicate that activation of PKA or PKC in HL-60 cells may confer protection
      against MLII-induced apoptosis.

PMID- 10952033
TI  - The water extract of Jagamchotang protects the ischemia/reperfusion-induced
      cytotoxicity of rat neonatal myocardial cells via generation of nitric oxide.
AB  - Jagamchotang has been used for treatment of ischemic myocardial diseases in
      Chinese traditional medicine. However, little is known about the mechanism by
      which Jagamchotang rescues myocardial cells from ischemic damages. To elucidate
      the protective mechanisms, the effects of Jagamchotang on ischemia/reperfusion
      induced cytotoxicity and generation of nitric oxide (NO) are investigated in
      primary neonatal myocardial cells. Ischemia/reperfusion itself induces severe
      myocardial cell death in vitro. However, treatment of the cells with Jagamchotang
      significantly reduces both ischemia/reperfusion-induced myocardial cell death and
      LDH release. In addition, pretreatment of Jagamchotang before reperfusion
      recovers the lose of beating rates after ischemia/reperfusion. For a while, the
      water extract of Jagamchotang stimulates myocardial cells in ischemic condition
      to produce nitric oxide (NO) in a dose dependent manner and it protects the
      damage of myocardial cells. Furthermore, the protective effects of the water
      extract of Jagamchotang is mimicked by treatment of sodium nitroprusside, an
      exogenous NO donor. NG-monomethyi-L-argine (NGMMA), a specific inhibitor of
      nitric oxide synthase (NOS), significantly blocks the protective effects of
      Jagamchotang on the cells after ischemia/reperfusion. Taken together, we suggest
      that the protective effects of Jagamchotang against ischemia/reperfusion-induced
      myocardial damages may be mediated by NO production during ischemic condition.

PMID- 10952034
TI  - Production of hydrogen peroxide by serum and its involvement in cell
      proliferation in ROS 17/2.8 osteoblasts.
AB  - The effects of hydrogen peroxide, which fetal bovine serum (FBS) releases, on
      proliferation have been studied in ROS 17/2.8 osteoblasts. Cell proliferation,
      when activated by FBS, was inhibited by catalase in ROS 17/2.8 osteoblasts, but
      did not in primary osteoblast-like cells. Serum-induced extracellular signal
      regulated kinase(ERK) activity was reduced by the pretreated catalase in ROS
      17/2.8 osteoblasts. In addition, the present studies demonstrate that addition of
      FBS led to an increase of fluorescence of dihydrorhodamine 123, indicating
      formation of free radicals including hydrogen peroxide in ROS 17/2.8 osteoblasts,
      but not in primary osteoblast-like cells. These phenomena may account for the
      generation of reactive oxygen species during cellular proliferation in ROS 17/2.8
      osteoblasts.

PMID- 10952035
TI  - Behavioral and immune changes in v-Ha-ras transgenic mice.
AB  - Transgenic mice (Oncomice) with an activated v-Ha-ras oncogene under the control
      of the mouse mammary tumor virus promoter develop mammary tumors. We wondered if
      the expression of the v-Ha-ras oncogene product would induce changes in mice
      behavioral activity, that could be associated with alterations in their immune
      system. Behavior was evaluated in an open field study considering line crossings
      and rears. Oncomice consistently showed less activity than FVB mice. Lieber
      DeCarli diet decreased both types of activity in both strains. Cocaine treatment
      increased line crossings in both strains. Oncomice spleen and thymus cell
      supernatants contained higher levels of IL-2. Oncomice serum had higher levels of
      IL-1alpha. Our results suggest a direct association between higher levels of IL
      1alpha and lower open field activity. Therefore, we can infer that the increased
      level of IL-1alpha found in Oncomice, could have a key role in oncogene induced
      immune and behavioral changes, and could be a requirement to facilitate its
      transforming activity.

PMID- 10952036
TI  - Omeprazole inhibits phagocytosis and acidification of phagolysosomes of normal
      human neutrophils in vitro.
AB  - We postulated omeprazole inhibition of the neutrophil proton pump, impairing
      phagocytosis and phagolysosomal acidification. Neutrophils from healthy human
      beings were treated with omeprazole prodrug 0.5 mM/l or acid activated omeprazole
      0.5 mM/l, then incubated with killed Saccharomyces cerevisiae stained with
      bromcresol purple. Wet mounts were done at 10, 30 and 60 minutes. Percent
      neutrophils phagocytosing, percent yeast phagocytosed, and yeast per
      phagocytosing neutrophil were significantly decreased in acid activated
      omeprazole compared to controls and omeprazole prodrug. In contrast, percent
      acidification of intracellular yeast was significantly lower in both omeprazole
      prodrug and acid activated omeprazole compared to controls. Over time, control
      neutrophils showed an increase in percent yeast phagocytosed and yeast per
      phagocytosing neutrophil. When treated with acid activated omeprazole, the
      percent of neutrophils phagocytosing progressively decreased over time. We
      observed 1) omeprazole prodrug does not inhibit neutrophil phagocytosis but does
      inhibit phagolysosomal acidification, whereas 2) acid activated omeprazole
      inhibits both neutrophil phagocytosis and phagolysosome acidification. We
      conclude that omeprazole impairs these neutrophil functions in vitro.

PMID- 10952037
TI  - Cocaine inhibits human neutrophil phagocytosis and phagolysosomal acidification
      in vitro.
AB  - Cocaine, used intravenously, increases the risk of infections, but its effects on
      neutrophil phagocytosis have not been examined in vitro. Human neutrophils were
      suspended in cocaine hydrochloride 0, 1, 10, 50, 100 or 200 microg/ml in Hank's
      balanced salt solution to which was added a phagocytic meal of killed
      Saccharomyces cerevisiae stained with the pH indicator dye bromcresol purple.
      Yeast per phagocytosing neutrophil and the percent neutrophils phagocytosing
      yeast were reduced in neutrophils treated with cocaine 100 and 200 microg/ml (P <
      0.05). When examined for percent of yeast phagocytosed after 10 minutes,
      neutrophils treated with cocaine 1-200 microg/ml demonstrated a decrease (P <
      0.05). However, at 60 minutes only neutrophils treated with cocaine 50 and 100
      microg/ml still showed a decrease in percent of yeast phagocytosed.
      Phagolysosomal acidification was impaired in neutrophils treated with 50, 100 and
      200 microg/ml cocaine. Thus, cocaine inhibits neutrophil phagocytosis and
      phagolysosomal acidification in vitro, offering a reason for cocaine
      users/abusers to have impaired host defense and to be potentially at higher risk
      for infections.

PMID- 10952038
TI  - High density insulin receptor-positive diabetogenic T lymphocytes in nonobese
      diabetic mice are memory cells.
AB  - Our previous work examining the importance of insulin receptor (IR) expression on
      T cells has demonstrated that when T cells from nonobese diabetic mice were
      sorted into populations expressing a high (IR(High)) and a low (IR(Low)) density
      of IR, IR(High) T cells rapidly transferred insulitis and diabetes. We have
      further characterized IR(High) T cells. Both CD4+ and CD8+ cells were detected in
      the IR(High) T cell population, but IR(High) expression was detected
      predominantly on CD4+ cells. IRHigh T cells were polyclonal for TCR Vbeta-chain
      expression. By 3 color flow cytometric analysis, virtually all IR(High) T cells
      expressed low or negligible levels of CD62L (CD62L(Low)/-) and high levels of
      CD44 (CD44(High)). The lack of IL-2 receptor and transferrin receptor expression
      as seen previously, together with the CD62L(Low)/- CD44(High) phenotype suggests
      that IR(High) T cells are memory cells. However, since only about one quarter of
      all of the CD62L(Low)/- or CD44(High) T cells were also IR(High), the IR(High)
      phenotype defines a subpopulation of memory T cells that are aggressively
      diabetogenic.

PMID- 10952039
TI  - 2000 and beyond: the dawning of a second golden medical era?

PMID- 10952040
TI  - Radiologic case study. Rupture of the long head of the biceps tendon.
AB  - Rupture of the long head of the biceps tendon frequently is encountered in the
      setting of coexisting rotator cuff pathology and chronic impingement, but
      traumatic rupture is occasionally seen, as in this case. Signs and symptoms are
      not always diagnostic, and MRI or MR arthrography can be a useful tool for
      evaluation of the tendon in difficult cases. Ideally, an empty bicipital groove
      is seen, indicating absence of the tendon and rupture. Scar tissue within the
      groove can be problematic, and correlation with oblique coronal and sagittal
      images is always recommended. The superior labrum at the attachment of the
      bicipital anchor should always be inspected carefully, as this is the most common
      site of rupture, and there may be an associated tear of the superior labrum.
      Magnetic resonance arthrography is not necessary for diagnosis in most cases, but
      will provide better visualization of the tendon and bicipital-labral complex.

PMID- 10952041
TI  - Silicone block interposition for traumatic bone loss.
AB  - In situations where bone is lost secondary to trauma, the use of a hand-carved
      silicone block provides good results. When bone grafting is undertaken, a well
      defined membrane will have enveloped the implant. Incising the membrane allows
      easy block removal, and after freshening the bone ends, a cavity awaits the bone
      graft. This technique offers simplicity and adequate stability for therapy, and
      secondary bone grafting is facilitated by the created space.

PMID- 10952042
TI  - Interlocking intramedullary nailing in distal tibial fractures.
AB  - This retrospective study examined the results of non-pilon fractures of the
      distal part of the tibia treated with interlocking intramedullary nailing.
      Seventy-three patients with equal numbers of fractures treated surgically between
      1990 and 1998 were reviewed. Mean patient age was 39.8 years, and follow-up
      averaged 34.2 months. The AO fracture classification system was used. Concomitant
      fractures of the lateral malleolus were fixed. All but three fractures achieved
      union within 4.2 months on average. Satisfactory or excellent results were
      obtained in 86.3% of patients. These results indicate interlocking intramedullary
      nailing is a reliable method of treatment for these fractures and is
      characterized by high rates of union and a low incidence of complications.

PMID- 10952043
TI  - Long-term mechanical stability of the impacted morselized graft-cement interface
      in total joint replacement: an experimental study in dogs.
AB  - This experimental study compared the long-term (12 months) mechanical stability
      of the morselized graft-cement interface with the conventional bone-cement
      interface in both femoral bones of 10 adult dogs. For mechanical testing, three
      point bending and push-out loading tests of composite bone-cement beams were
      used, while the incorporation of the graft was assessed by serial radiographs.
      Although the parameters fracture load and interface failure load showed inferior
      values in the specimens with a morselized graft-cement interface compared to
      those in specimens with a conventional bone-cement interface, no statistically
      significant differences were found between groups. Radiographic reconstitution of
      the lateral femoral cortex was observed in all animals at 3 months while signs of
      advanced remodeling were apparent at 6 months. These results indicate the long
      term mechanical stability of the impacted morselized graft-cement interface is
      comparable to that of the conventional bone-cement interface created in primary
      total hip replacements provided the grafted area is protected from early heavy
      loading.

PMID- 10952044
TI  - Influence of orthotopic placement on the incorporation and mechanical strength of
      a loaded structural cortical graft: an experimental study in rabbits.
AB  - The biological and mechanical behavior of loaded cortical autografts were
      evaluated in an experimental study using 40 adult male New Zealand rabbits
      divided into 4 groups. A double osteotomy was performed on all animals at the mid
      diaphysis of the right ulna. The bone segment (5 mm) in between the osteotomies
      was considered a cortical autograft and fixed with an intramedullary Kirschner
      wire. The graft was fixed in an orthotopic manner in groups A and C, and rotated
      180 degrees in groups B and D. After the animals were sacrificed (at 2 months for
      groups A and B and at 4 months for groups C and D), bone mineral density, graft
      cross-sectional geometry, and SSI index were assessed. Mechanical testing of the
      grafted area was carried out using a three-point bending configuration, and the
      parameter fracture load was assessed. Graft union and incorporation also was
      studied in histologic sections. In group C (orthotopic graft placement--4
      months), bone specimens showed statistically significantly higher values for
      fracture load, total cross-sectional area, volumetric total bone mass and
      density, and polar SSI (P values < or = .05) compared to the other groups. In the
      same group, union and incorporation of the graft was complete, the cortex showed
      low porosity, and the collagen fibers were mature and properly oriented.
      Structural cortical bone autografts placed in an orthotopic manner recognize the
      new mechanical environment as optimal and thus their biological and mechanical
      behavior are enhanced. Loaded structural cortical grafts should be placed in an
      orthotopic manner when used for the management of cortical bone defects.

PMID- 10952045
TI  - Epidemiology, demographics, and natural history of congenital hip disease in
      adults.
AB  - This study examined the epidemiology and demographics of congenital hip disease
      in 468 (660 hips) patients who were examined between 1970 and 1996. In 356 (54%)
      hips, the diagnosis was secondary osteoarthritis due to congenital hip disease,
      and in 272 (41%) hips, the diagnosis was idiopathic osteoarthritis. In the
      remaining 32 (5%) hips, the diagnosis was uncertain. Of the hips with congenital
      hip disease, 170 (47.7%) hips were dysplastic, 85 (23.9%) had low dislocation,
      and 101 (28.4%) high dislocation. The majority of patients with congenital hip
      disease were women (338 [95%] hips). The natural history of the three types of
      congenital hip disease was studied in 157 patients (202 hips: 102 dysplastic, 42
      low dislocation, and 58 high dislocation) who had received no treatment before
      the initial examination. Average length of follow-up was 17 years. In dysplastic
      hips, the disease remained undiagnosed until the onset of symptoms at an average
      age of 34.5 years. In patients with low dislocation, pain had started at an
      average of 32.5 years due to progressive degenerative arthritis within the false
      acetabulum. In patients with high dislocation, in the presence of a false
      acetabulum, pain started at an average age of 31.2 years, while in its absence,
      pain started at an average age of 46.4 years due to muscle fatigue. These
      findings suggest dysplasia, low dislocation, and high dislocation in adults are
      the results of untreated dysplasia, subluxation, and complete dislocation in
      infancy, respectively.

PMID- 10952046
TI  - Risk factors for idiopathic scoliosis: review of a 6-year prospective study.
AB  - This study identified factors associated with the prevalence of idiopathic
      scoliosis and curve evolution in schoolchildren from northwestern and central
      Greece. A total of 85,627 children aged 9-15 years were screened for scoliosis. A
      subset of children with curves of at least 10 degrees underwent clinical and
      radiographic follow-up. The total population screened and the cohort followed for
      curve progression were evaluated according to factors associated with curve
      evolution. The prevalence of scoliosis was 1.7%, with most cases appearing at
      ages 13 and 14 years and small scoliotic curves (10 degrees-19 degrees) being
      most prevalent (prevalence 1.5%). Prevalence was associated with gender; age; and
      magnitude, apex, and direction of the curve. Progression of the curve occurred in
      14.7% of 839 children, while 27.4% demonstrated spontaneous improvement of at
      least 5 degrees. A high risk of curve progression was associated with the
      following: sex--girls, curve pattern--right thoracic and double curves in girls
      and right lumbar in boys, maturity--girls before the onset of menses, age--time
      of pubertal growth spurt, and curve magnitude--curves > or = 30 degrees. Although
      only a small percentage of scoliotic curves undergo progression, the pattern of
      the curve according to curve direction and the sex of the child plays a
      significant role in the ability to identify which curves will progress.

PMID- 10952047
TI  - Ganglions of the proximal interphalangeal joint.
AB  - Ganglions of the proximal interphalangeal joint are uncommon. Six patients (nine
      ganglions) were treated surgically. The lesions presented on the ulnar aspect of
      the extensor mechanism between the lateral band and the central slip and
      communicated with the joint by means of a stalk. Mild degenerative joint disease
      was noted in each case. Surgical excision provided relief of symptoms, and no
      patient has experienced any recurrence to date.

PMID- 10952048
TI  - Anterior approach to the cervical spine: surgical anatomy.
AB  - While performing the anterior approach to the cervical vertebral bodies, injury
      to important anatomic structures in the vicinity of the dissection represents a
      serious risk. The midportion of the recurrent laryngeal nerve and the external
      branch of the superior laryngeal nerve are encountered in the anterior approach
      to the lower cervical spine. The recurrent laryngeal nerve is vulnerable to
      injury on the right side, especially if ligation of inferior thyroid vessels is
      performed without paying sufficient attention to the course and position of the
      nerve, and the external branch of the superior laryngeal nerve is vulnerable to
      injury during ligature and division of the superior thyroid artery. Avoiding
      injury to the recurrent laryngeal nerve (especially on the right side) and
      superior laryngeal nerve is a major consideration in the anterior approach to the
      lower cervical spine. The sympathetic trunk is situated in close proximity to the
      medial border of the longus colli at the C6 level (the longus colli diverge
      laterally, whereas the sympathetic trunk converges medially). The damage leads to
      the development of Horner's syndrome with its associated ptosis, meiosis, and
      anhydrosis. Awareness of the regional anatomy of the sympathetic trunk may help
      in identifying and preserving this important structure while performing anterior
      cervical surgery or during exposure of the transverse foramen or uncovertebral
      joint at the lower cervical levels. Finally, the spinal accessory nerve (embedded
      in fibroadipose tissue in the posterior triangle of the neck) is prone to injury.
      Its damage will result in an obvious shoulder droop, loss of shoulder elevation,
      and pain. Prevention of inadvertant injury to the accessory nerve is critical in
      the neck dissection.

PMID- 10952049
TI  - Complete closed posterior talus dislocation without fracture.

PMID- 10952050
TI  - Therapeutic embolization for sustained hemorrhage following total hip replacement
      in a patient with hemophilia A.

PMID- 10952051
TI  - Extradigital glomus tumor as a cause of buttock pain.

PMID- 10952052
TI  - Vertebral body osteopenia in an uninstrumented spinal fusion.

PMID- 10952053
TI  - Trichorhinophalangeal syndrome: evolution of Perthes-like changes in the hips.

PMID- 10952055
TI  - Recent advances in neurotrauma.
AB  - The frequency of and outcome from acute traumatic brain injury (TBI) in humans
      are detailed together with a classification of the principal focal and diffuse
      pathologies, and their mechanisms in extract laboratory models are outlined.
      Particular emphasis is given to diffuse axonal injury, which is a major
      determinant of outcome. Cellular and molecular cascades triggered by injury are
      described with reference to the induction of axolemmal and cytoskeletal
      abnormalities, necrotic and apoptotic cell death, the role of Ca2+, cytokines and
      free radicals, and damage to DNA. It is concluded that TBI in humans is
      heterogeneous, reflecting various pathologies in differing proportions in
      patients whose genetic background (APOE gene polymorphisms) contributes to the
      outcome at 6 months. Although considerable progress has been made in the
      understanding of TBI, much remains to be determined. However, a deeper
      understanding of the pathophysiological events may lead to the possibility of
      improving outcome from rational targeted therapy.

PMID- 10952054
TI  - Current concepts in the evaluation and treatment of osteosarcoma.

PMID- 10952056
TI  - Intracellular processing and toxicity of the truncated androgen receptor: nuclear
      congophilia-associated cell death.
AB  - The pathogenesis of the selective motor neuron death in spinal bulbar muscular
      atrophy (SBMA) is not fully understood. Similar to observations with other mutant
      polyglutamine (poly Q) expanded proteins, truncated androgen receptor (AR) with
      expanded poly Q tract cause intracellular aggregates; however, the precise
      relationship between aggregates and disease pathogenesis is unresolved. In order
      to have a better understanding of the cellular processing and toxicity of the
      mutant AR, we focused on a short N-terminal portion of AR containing normal or
      expanded poly Q repeats, and have carried out biochemical, immunocytochemical,
      cytochemical and ultrastructural studies of BHK cells at different intervals
      after transfection. In cells expressing mutant truncated AR, using an anti-AR N
      terminal antibody, we observed no immune staining in the nucleus and identified
      immune negative aggregates surrounded by immunopositive material in the
      cytoplasm. Congo red staining identified a component of aggregates with a beta
      pleated secondary structure in both cytosol and nucleus, while electron
      microscopy revealed a fibrillary-granular material as the ultrastructural
      correlate. In addition, acid phosphatase staining and ubiquitin
      immunocytochemistry demonstrated that in transfected cells, both lysosomal and
      nonlysosomal degradation systems are actively involved in handling the mutant
      truncated AR. The temporal relationship of nuclear congophilia to a subsequent
      massive cell death suggests that entry of proteolytic cleavage products into the
      nucleus, perhaps the expanded poly Q stretch itself, may play an important role
      in cell toxicity.

PMID- 10952057
TI  - Extensive injury of descending neurons demonstrated by retrograde labeling in a
      virus-induced murine model of chronic inflammatory demyelination.
AB  - Persistent Theiler's virus infection of SJL/J mice was used as a model to
      quantitatively assess the extent of descending neuron injury by chronic
      inflammatory demyelination of the spinal cord. By 9 months postinfection,
      inflammatory demyelinating lesions were present throughout the spinal cord,
      affecting up to 31% of the cross-sectional area of the ventrolateral columns.
      Axon dropout was evident in the lesions by electron microscopy and by
      quantitation of axons in normal-appearing white matter. Axon number in the
      ventrolateral columns at L1/L2 was reduced by 23% and total axon area was reduced
      by 37%, compared with uninfected mice. The most informative data on descending
      neuron injury, however, was a reduction in retrograde. Fluoro-Gold labeling.
      Labeling from T11/T12 of rubrospinal, reticulospinal/raphespinal, and
      vestibulospinal neurons was reduced by 60%, 70%, and 93%, respectively.
      Retrograde responses to axonal injury were observed, consisting of atrophied cell
      bodies, indented nuclei, and abundant lipofuscin, but cell body dropout was
      minimal. The number of cell bodies of vestibulospinal neurons was reduced by only
      35%, whereas the number of cell bodies of rubrospinal neurons was unchanged.
      These results demonstrate that chronic inflammatory demyelination can severely
      injure axons and emphasize the need to design neuroprotective therapies in human
      multiple sclerosis.

PMID- 10952058
TI  - Cytogenetic analysis of gemistocytic cells in gliomas.
AB  - Gemistocytes are glial cells characterized by voluminous, eosinophilic cytoplasm
      and a peripherally positioned, often flattened nucleus. Gemistocytes, usually
      present in anoxic-ischemic brains, are regularly encountered in glial neoplasms.
      The presence of gemistocytes in gliomas has been associated with an unfavorable
      clinical course, notwithstanding the low proliferative potential of these cells.
      It is not known whether gemistocytes residing in gliomas are dormant tumor cells,
      or alternatively, represent interspersed reactive glial cells. Whereas
      gemistocytic astrocytomas have been subject to various genetic investigations, no
      genomic analysis comparing individual cells in gliomas has been reported so far.
      In the present study, 3 astrocytomas, 3 oligodendrogliomas, and 3 mixed
      oligoastrocytomas, all harboring gemistocytic cells, were genetically analyzed by
      DNA in situ hybridization to paraffin-embedded, formalin-fixed tissue samples
      with optimal preservation of cellular morphology. To this end, probes for the
      centromeric regions of chromosome 7 and 10, known to show copy number aberrations
      in gliomas, were used. In addition, probes for centromeric regions of chromosomes
      1 and 17 were used for the ploidy status of the tumors. The spot counts for the
      various chromosomes were statistically compared. Gains of chromosome 7 were found
      in 1 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, and 1 anaplastic
      oligoastrocytoma. Loss of chromosome 10 was seen in 2 anaplastic astrocytomas, in
      1 anaplastic oligodendroglioma, and in 1 anaplastic oligoastrocytoma. In 3 cases,
      significant differences in spot distributions between gemistocytes and non
      gemistocytes were found, but the other cases showed no difference in spot
      distribution. It is concluded that, although many gemistocytic cells in gliomas
      may be considered reactive cells, in a subset of tumors, part of the gemistocytic
      cells should be considered neoplastic.

PMID- 10952059
TI  - Epidermal growth factor and fibroblast growth factor 2 cause proliferation of
      ependymal precursor cells in the adult rat spinal cord in vivo.
AB  - We investigated the mitogenic effect of continuous intrathecal infusion of
      epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF2) on ependymal
      precursor cells of the adult rat spinal cord in vivo. Either EGF, FGF2, EGF plus
      FGF2, or artificial cerebrospinal fluid (aCSF) was infused at a flow rate of 0.5
      microl/h (15 ng/h of EGF or FGF2) for 3 or 14 days into the intrathecal space at
      T1 through a catheter attached to an osmotic minipump. To assess proliferation,
      the bromodeoxyuridine (BrdU) labeling index (LI) in the ependyma at T1 was
      calculated at 3 or 14 days. At 3 days there was no statistical difference in LI
      between these groups, but at 14 days the LI was significantly higher in the EGF
      plus FGF2 group (27.2% = 16.0%) than in the aCSF group (5.4% +/- 4.7%; p < 0.05).
      With EGF alone or FGF2 alone, the LI increases were not significantly different
      from the aCSF group. With EGF plus FGF2 for 14 days, some BrdU-positive cells in
      the ependyma also expressed nestin. These results suggest that the intrathecal
      infusion of EGF plus FGF2 has a mitogenic effect on precursor cells in the
      ependyma of the adult rat spinal cord.

PMID- 10952060
TI  - Corpora amylacea and heat shock protein 27 in Ammon's horn sclerosis.
AB  - Increased numbers of corpora amylacea have been observed in the resected mesial
      temporal lobe of many patients with complex partial seizures (CPS) and Ammon's
      horn sclerosis (AHS). Several heat shock proteins (HSPs) are induced by seizures
      and have been suggested as an etiologic factor in the formation corpora amylacea.
      We quantified corpora amylacea and HSP27-immunoreactive astrocytes in temporal
      lobe specimens from patients with CPS (28 AHS; 10 non-AHS) and in 5 autopsy
      controls. Corpora amylacea were increased in each sector of Ammon's horn in the
      AHS group, significantly so in CA1 and CA3 (p < 0.0001 and p = 0.0097,
      respectively), compared with the non-AHS group, although there was considerable
      variability among the specimens. We found HSP27 to be significantly but
      nonspecifically increased in the resected temporal lobe specimens from all
      patients with CPS, regardless of the underlying pathology. HSP27 was not,
      however, expressed within the corpora amylacea, and did not correlate with the
      number of corpora amylacea in any of the 9 mesial and lateral temporal lobe areas
      examined.

PMID- 10952061
TI  - Autoradiography of glutamate receptor binding in adult Lurcher mutant mice.
AB  - The mutation Lurcher, resulting from a gain of malfunction of the delta2
      glutamate receptor expressed specifically by cerebellar Purkinje cells, causes a
      primary total loss of these neurons of the cerebellar cortex, as well as the
      secondary degeneration of cerebellar granule and inferior olive neurons. The
      distributions of glutamate receptors sensitive to amino-methylisoxazole-propionic
      acid (AMPA), to kainic acid (KA), and to N-methyl-D-aspartic acid (NMDA) as well
      as metabotropic sites (MET1 and MET2) were examined in wild type and Lurcher mice
      by quantitative autoradiography. This study was undertaken to determine the gene
      effect on the distribution of the various glutamate receptor subtypes, as well as
      how the cerebellar lesion affects the glutamatergic system in other brain
      regions. In cerebellum, there were postsynaptic AMPA and metabotropic receptors
      on Purkinje cells, postsynaptic NMDA receptors on granule cells, as well as KA
      receptors on granule cells or on parallel fibers. Taking into account surface
      areas, binding to all receptor subtypes was lower in the cerebellar cortex of
      Lurcher mutants than in wild type mice, while in the deep cerebellar nuclei only
      KA receptors were diminished. In other brain regions, the alterations followed
      always the same pattern characterized by a decrease of NMDA and KA receptors but
      with an increase of AMPA sites; these reciprocal changes were seen in thalamus.
      neostriatum, limbic regions, and motor cerebral cortical regions. Comparisons of
      glutamate receptor distribution in Lurcher mutants and in human autosomal
      cerebellar ataxia may permit further understanding of the role of glutamate
      induced toxicity on neuronal death in these heredo-degenerative diseases.

PMID- 10952062
TI  - Amyloid beta protein (Abeta) starts to deposit as plasma membrane-bound form in
      diffuse plaques of brains from hereditary cerebral hemorrhage with amyloidosis
      Dutch type, Alzheimer disease and nondemented aged subjects.
AB  - To clarify where and how beta-amyloid begins to deposit in senile plaques, we
      examined the ultrastructural localization of amyloid beta protein (Abeta) in
      diffuse plaques of brains with hereditary cerebral hemorrhage with amyloidosis
      Dutch type. Alzheimer disease (AD), and from nondemented aged subjects. Serial
      ultrathin sections of osmium-plastic blocks were immunogold-labeled for Abetax-42
      (Abeta42), and sections on grids were observed under the electron microscope (EM)
      after observing the exact localization of the diffuse plaques in sections on
      glass slides by the reflection contrast microscope. Abeta42 deposition, which was
      decollated with gold particles, appeared in 3 forms in all subjects under the EM:
      1) Scattered small bundles of amyloid fibrils between cell processes, frequently
      seen in the densely stained area of diffuse plaques. 2) Scattered small foci of
      nonfibrillar materials between cell processes as a relatively minor form. 3)
      Abeta42 on a part of the cell surface plasma membrane of normal appearing cell
      processes, a major form in weakly immunostained areas. The last form was not
      associated with degenerative neurites or reactive glia. Abeta42 deposition on the
      cell surface plasma membrane appears to be an initial event in diffuse plaques,
      and then it develops into amorphous/fibrillar amyloid between cell processes.

PMID- 10952063
TI  - Sequence of Abeta-protein deposition in the human medial temporal lobe.
AB  - The deposition of Abeta protein (Abeta) and the development of neurofibrillary
      changes are important histopathological hallmarks of Alzheimer disease (AD). In
      this study, the medial temporal lobe serves as a model for the changes in the
      anatomical distribution pattern of different types of Abeta-deposits occurring in
      the course of AD, as well as for the relationship between the development of
      Abeta-deposition and that of neurofibrillary pathology. In the first of 4 phases
      of beta-amyloidosis, diffuse non-neuritic plaques are deposited in the basal
      temporal neocortex. The same plaque type appears in the second phase within the
      external entorhinal layers pre-beta and pre-gamma, and fleecy amyloid deposits
      occur in the internal entorhinal layers pri-alpha, pri-beta, pri-gamma, and in
      CA1. In the third phase, Abeta-deposits emerge in the molecular layer of the
      fascia dentata, and band-like Abeta-deposits occur in the subpial portion of the
      molecular layer of both the entorhinal region and the temporal neocortex. In
      addition, confluent lake-like Abeta-deposits appear in the parvopyramidal layer
      of the presubicular region. The fourth phase is characterized by diffuse and core
      only plaques in CA4. Diffuse plaques evolve sporadically in the external
      entorhinal layer pre-alpha. Parallel to the evolution of beta-amyloidosis as
      represented by the 4 phases, neuritic plaques gradually make their appearance in
      the temporal neocortex, entorhinal region, CA1, the molecular layer of the fascia
      dentata, and CA4. A prerequisite for their development is the presence of Abeta
      and the presence of neurofibrillary tangles in neurons targeting the regions
      where neuritic plaques evolve. Each of the different types of Abeta-deposits,
      including neuritic plaques, plays a specific role in the distinct developmental
      sequence as represented by the 4 phases so that the medial temporal lobe
      inexorably becomes involved to an ever greater extent. The step-for-step
      involvement of connected anatomical subfields highlights the importance of the
      entorhino-hippocampal pathways for the expansion of beta-amyloidosis. The 4
      phases in the evolution of beta-amyloidosis correlate significantly with the
      stages of the neurofibrillary pathology proposed by Braak and Braak.

PMID- 10952064
TI  - DNA vaccines.
AB  - DNA vaccination or genetic immunization is a rapidly developing technology that
      offers new approaches for the prevention and therapy of disease. Regarding the
      inoculation method of DNA vaccine, we recommend the gene gun delivery system,
      which is a highly reliable method compared to intramuscular inoculation. DNA
      vaccines could have potential advantages over other types of vaccines in that
      these vaccines can induce strong cellular immune responses, cytotoxic T
      lymphocytes and type 1 helper T cells, without resorting to live organisms or
      complicated protein formulation. The cellular immune responses are especially
      required for the protection against infections with intracellular pathogens such
      as viruses and Mycobacterium tuberculosis and protection against cancers,
      suggesting that they seem to be suitable targets of DNA vaccines. We describe
      here that their application to bacterial infections requires optimization of
      codon usage in the DNA vaccines to the host animal to improve translational
      efficiencies of the bacteria genes. DNA vaccines for a variety of pathogens and
      cancers have now entered phase I/II human clinical trials.

PMID- 10952065
TI  - Frequency- and time-dependent effects of fendiline on action potentials of guinea
      pig papillary muscle.
AB  - The action of fendiline on cardiac electrical activity was investigated in guinea
      pig papillary muscle by monitoring frequency- and time-dependent changes in
      membrane potential, action potential (AP) configuration and conduction velocity.
      Isolated guinea pig papillary muscles driven at 0.1 to 3 Hz showed a
      concentration-dependent reduction of +Vmax, overshoot, and AP duration at -20mV
      (APD20) in the presence of fendiline (1-320 microM), reflecting inhibition of Na+
      and L-type Ca2+ channels, respectively. No significant change in resting
      potential and AP duration at 90% repolarization (APD90) were observed. Inhibition
      of +Vmax and APD20 was more prominent at higher frequency of stimulation (2 Hz)
      than at lower ones (0.2 Hz), demonstrating frequency-dependent block of Na+ and
      Ca2+ channels including an open channel block. A good relationship between
      changes in +Vmax and APD20 suggested some commonality in the mechanism of
      inhibition of Na+ and Ca2+ channels by fendiline. Time-dependence of effects of
      fendiline, observed in presence of bolus dose (200 microM), showed an earlier
      onset of inhibition of +Vmax and APD20, particularly at higher frequencies.
      Missed beats and conduction block also appeared earlier in preparations driven at
      higher frequency. These findings suggest a frequency-dependent (and open channel)
      block of Na+ and Ca2+ channels by fendiline, leading to inhibition of fast and
      slow conduction in addition to its reported inactivated Ca2+ channel block.

PMID- 10952066
TI  - Effects of rifampin on the glutathione depletion and cytochrome c reduction by
      acetaminophen reactive metabolites in an in vitro P450 enzyme system.
AB  - The present study examined whether rifampin attenuated glutathione (GSH)
      depletion by acetaminophen reactive metabolites generated in the in vitro P450
      enzyme system prepared from mouse liver and the possible mechanism involved in
      this effect. The results showed that GSH concentration was decreased
      concentration-dependently by acetaminophen in the in vitro P450 enzyme system.
      Rifampin significantly attenuated acetaminophen-mediated GSH depletion in a
      concentration-dependent manner. The concentration-response curve for GSH
      depletion of acetaminophen was shifted to the right in a parallel fashion in the
      presence of rifampin at the concentration of 3.2 x 10(-5) M, which appeared to
      result from the competitive binding of rifampin to acetaminophen metabolites.
      Cytochrome c was markedly reduced by acetaminophen metabolites in this enzyme
      system, and GSH concentration-dependently increased the cytochrome c reduction by
      acetaminophen metabolites. These findings suggested that cytochrome c was reduced
      by the GSH conjugate of acetaminophen metabolites rather than by acetaminophen
      derived superoxide anion (O2*-) and other unbound free radicals. Rifampin was
      shown to possess an effect similar to that of GSH. It is concluded that the
      decrease in GSH depletion by rifampin is most likely attributable to the binding
      of rifampin to the acetaminophen toxic species, and the increase in cytochrome c
      reduction by rifampin is attributable to the conjugate formed between rifampin
      and acetaminophen metabolites.

PMID- 10952067
TI  - YM-40461, a potent surfactant secretagogue, improves mucociliary clearance in SO2
      exposed guinea pigs.
AB  - The effects of the new pulmonary surfactant secretagogue YM-40461, 1-(2
      dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl) urea, on tracheal mucociliary
      transport (MCT) were assessed using guinea pigs with acute bronchitis. Acute
      bronchitis was induced by SO2 gas exposure (400 ppm for 3 h). MCT velocity was
      measured by means of the dye gelatin technique. YM-40461 at doses of 1-10 mg/kg,
      p.o. induced recovery of MCT function, with an ED50 value of 2.4 mg/kg. Maximal
      recovery (78.0+/-12.5%) was observed 2 h in the animals treated with 10 mg/kg of
      YM-40461. Ambroxol and bromhexine showed less effect on the MCT dysfunction than
      YM-40461. An artificial surfactant (Surfacten) also aided recovery. YM-40461 at a
      dose of 10 mg/kg, p.o. significantly improved surfactant production without
      affecting mucus secretion. These results show that YM-40461 ameliorates MCT
      dysfunction caused by SO2 exposure by activation of pulmonary surfactant
      secretion.

PMID- 10952068
TI  - Dissociation of potentiation of Leu31 Pro34 neuropeptide Y on adrenergic and
      purinergic transmission in isolated canine splenic artery.
AB  - The present study observed the effects of an activation of neuropeptide Y (NPY)
      Y1 receptors on adrenergic and purinergic components of double-peaked
      vasoconstrictor responses to periarterial nerve stimulation in the isolated,
      perfused canine splenic arteries. The results showed that 3-30 nM Leu31 Pro34
      neuropeptide Y (LP-NPY) produced a dose-dependent potentiation of double-peaked
      vasoconstrictor responses to trains of 30-s pulses at 1, 4 or 10 Hz of
      stimulation. The potentiation of LP-NPY of the nerve-stimulated vasoconstrictions
      were completely inhibited by subsequent blockade of alpha1-adrenoceptors or Y1
      receptors with 0.1 microM prazosin or with 1 microM BIBP 3226 ((R)-N2
      (diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininami de), respectively. The
      remaining responses in the presence of LP-NPY and prazosin were abolished by P2X
      receptor desensitization with 1 microM alpha,beta-methylene ATP. Moreover, 30 nM
      LP-NPY failed to modify the vasoconstrictor responses to nerve stimulation after
      treatment with prazosin. A subsequent administration of alpha,beta-methylene ATP
      completely suppressed the remaining responses after prazosin and LP-NPY. The
      vasoconstrictions induced by 0.003-1 nmol noradrenaline and 0.003-1 micromol ATP
      were slightly, but not significantly enhanced by 30 nM LP-NPY. The observations
      indicated that activation of postjunctional NPY Y1 receptors may have an
      important role in the modulation of adrenergic rather than purinergic
      transmission of the sympathetic co-transmission.

PMID- 10952069
TI  - Calcium polycarbophil, a water absorbing polymer, increases bowel movement and
      prevents sennoside-induced diarrhea in dogs.
AB  - The effects of calcium polycarbophil (CP), a water-absorbing polymer, on bowel
      movement were examined in comparison with known laxatives and anti-diarrheal
      agents in dogs, a species that resembles humans for stool output. CP increased
      stool frequency, fecal water content and fecal weight in a dose-dependent manner,
      but did not induce diarrhea. Sennoside and carboxymethylcellulose sodium (CMC-Na)
      increased fecal water content and induced diarrhea at lower doses than that which
      enhanced stool frequency. Trimebutine decreased stool frequency, fecal weight and
      fecal water content, resulting in inhibition rather than stimulation of
      defecation. In sennoside-induced diarrhea, loperamide and CP improved stool
      consistency and this was accompanied by reduced fecal moisture and frequency of
      diarrhea. In contrast, CMC-Na aggravated stool consistency with increased fecal
      water content and frequency of diarrhea, and trimebutine had little noticeable
      effect apart from reducing fecal weight. Our results show that CP has both
      laxative and anti-diarrheal effects in dogs and differed from conventional
      laxatives and anti-diarrheal agents. CP may be a suitable agent for treatment of
      idiopathic constipation, secretory diarrhea and irritable bowel syndrome with
      alternating constipation and diarrhea and with either predominating in terms of
      less side effects such as diarrhea or constipation.

PMID- 10952070
TI  - Examination of intrahepatic flow distribution by vital staining with rhodamine 6G
      in isolated perfused rat liver.
AB  - We previously reported that intrahepatic flow disturbance can be detected by
      vital staining of the liver with a fluorescent dye (Masuda et al., Biochem
      Pharmacol, 53, 1779-1787 (1997)). To evaluate further use of this method, a
      detailed study was performed. The isolated perfused rat liver was vitally stained
      with rhodamine 6G (R-6G) and perfusion-fixed, and cross and horizontal sections
      were examined by fluorescence microscopy. In the control liver, R-6G staining was
      localized to periportal hepatocytes and was distributed evenly throughout the
      liver, indicating a homogeneous perfusion. Finer examination of the thick
      sections and reconstruction of a three-dimensional flow pattern revealed
      intricate vascular networks together with the sinusoids in different portions of
      the liver. In a flow-redistribution model, i.e., under hepatic nerve stimulation,
      the extensive flow redistribution to the deeper portion of the liver was found to
      occur via short branches sprouted from large portal veins, with minimal perfusion
      of the liver margin. Thus, visualization of hepatic microvasculature enables
      anatomical analysis of flow disturbance. The method is indirect but simple and
      may help detect intrahepatic flow disturbance that could be evoked by various
      factors.

PMID- 10952071
TI  - Energy preserving effect of l-cis diltiazem in isolated ischemic and reperfused
      guinea pig hearts: a 31P-NMR study.
AB  - We determined the effect of 1-cis diltiazem, the enantiomer of diltiazem (d-cis
      isoform), on the energy metabolism of isolated guinea pig hearts during ischemia
      reperfusion. We used 31P-NMR to measure the high-energy phosphate content and
      intracellular pH (pHi) during global ischemia for 30 min followed by reperfusion
      for 30 min. Before ischemia, the left ventricular developed pressure (LVDP) was
      reduced less by 10 microM l-cis diltiazem than by 3 microM diltiazem or 500 nM
      nifedipine. However, 10 microM l-cis diltiazem preserved the intracellular ATP
      content during ischemia and reperfusion, reduced the end-diastolic pressure
      increase during ischemia and reperfusion, and restored LVDP after reperfusion.
      Nifedipine at 50 nM, which reduced the LVDP more than 10 microM l-cis diltiazem,
      showed no cardioprotective effect. Ten micromolar l-cis diltiazem and 3 microM
      diltiazem, but neither 50 nor 500 nM nifedipine, reduced the pHi decrease that
      occurred 25 or 30 min after the onset of ischemia. Therefore, l-cis diltiazem has
      a cardioprotective effect on ischemic and reperfused myocardium and is less
      cardiodepressive than diltiazem and nifedipine. The effect of l-cis diltiazem
      during ischemia and reperfusion involves energy preservation, which is probably
      independent of its Ca2+-channel blocking action.

PMID- 10952073
TI  - In vitro effects of Ginkgolide B on lymphocyte activation in atopic asthma:
      comparison with cyclosporin A.
AB  - The effects of Ginkgolide B (BN52021) on in vitro activation responses of human
      peripheral blood mononuclear cells (PBMC) from asthmatic patients was measured
      using 2-channel flow cytometric analysis of activation-associated cell surface
      antigens or ELISA assays for cytokines known to be expressed by PBMC during T1 or
      T2 immunological activation. BN52021 is an anti-inflammatory extract of Ginkgo
      biloba and has been used therapeutically. It is a known inhibitor of platelet
      activating factor (PAF), which is important in the pathogenesis of asthma, and
      may synergise with cyclosporin A (CyA) to inhibit pathogenic immune activation in
      asthmatics. We compared the inhibitory effects of BN52021 and CyA (1 microM each)
      on activation of PBMC of asthmatic patients stimulated by phorbol myristate
      acetate and calcium ionophore. Inhibition of production of the cytokines IL-4 and
      IL-5 by BN52021 was insignificant compared to CyA. However, BN52021 significantly
      reversed the increase in activation-associated CD45RA expression, with a trend
      towards decreased expression of HLA-DR. Lymphocyte activation markers were not
      significantly altered by CyA. Since they appear to have differing effects on
      activated cells, the anti-inflammatory effects of CyA and BN52021 in atopic
      asthma is potentially additive. The present approach may be useful for
      preliminary evaluation of novel therapeutic modalities for asthma treatment.

PMID- 10952072
TI  - Immunohistochemical demonstration of Cl- pump in type A intercalated cells of rat
      kidney.
AB  - In order to demonstrate the localization of an ethacrynic acid-sensitive Cl- pump
      in the rat kidney, immunohistochemical analysis was performed using an anti-Cl-
      pump antibody raised against rat brain Cl- pump protein with confocal laser
      scanning microscopy. The antibodies against Na+,K+-ATPase, aquaporin 2 and a type
      B intercalated cell marker, 43-kDa protein, were also used for comparison. Anti
      Cl- pump antibody recognized a 51-kDa renal protein of the same size as that in
      the brain on Western blots. Cl- -pump-like immunoreactivity was observed on the
      basolateral membranes of 42+/-3% of cortical collecting duct (CCD) cells and of
      38+/-1% of outer medullar collecting duct (OMCD) cells. Such immunoreactivity in
      CCD was sometimes co-localized with Na+,K+-ATPase, but in OMCD, the Cl- pump-like
      immunoreactivity co-existed with neither Na+,K+-ATPase, aquaporin 2 nor the type
      B intercalated cell marker 43-kDa protein. Thus, the Cl- pump was demonstrated to
      be localized on the basolateral membranes of type A intercalated cells of
      cortical and medullary collecting ducts in the rat kidney.

PMID- 10952074
TI  - Effect of the novel prostaglandin A1 derivative TEI-6363 on ROS17/2.8 cell
      differentiation in vitro.
AB  - The effect of TEI-6363 (5-[E-4-N,N-dimethylaminophenylmethylene]-4-hydroxy-2-[1
      methyl imidazole-2-ilthio]-4-[4-phenylbutyl]-2-cyclopentenone), a chemically
      synthesized prostaglandin A1 derivative, on cell proliferation and osteoblastic
      differentiation was investigated concurrently. ROS17/2.8 cells (a rat
      osteosarcoma-derived cell line) were treated with TEI-6363 at two concentrations,
      10(-7) and 10(-6) M, and viable cells were counted to assess cytotoxic effects
      and determine the growth curve. After 96 h of treatment, there was no evidence of
      any effect of TEI-6363 on cell viability at either concentration. However, a
      clear inhibitory effect on cell proliferation was observed after treatment with
      10(-6) M TEI-6363 for 24 h or longer. A pulse-treatment experiment showed that
      TEI-6363 induced the inhibition of proliferating ROS17/2.8 cells 24 h after
      addition. The inhibition of proliferation was associated with G1-arrest
      demonstrated by flow cytometric analysis, and incorporation of [3H]thymidine by
      ROS17/2.8 cells was decreased. Osteoblastic differentiation (assessed on the
      basis of increased alkaline phosphatase activity and collagen synthesis) was
      induced by TEI-6363 treatment at 10(-6) M following G1-arrest and inhibition of
      cell proliferation. These results suggest that TEI-6363 arrested the cell cycle
      of ROS17/2.8 cells at the G1 phase and induced osteoblastic differentiation.
      These results did not appear to be dependent on a marked cytotoxic effect.

PMID- 10952075
TI  - Relationship between effects of alcohol on psychomotor performances and blood
      alcohol concentrations.
AB  - Ethanol is a social drug and has been generally known to be a CNS depressant. A
      large fluctuation of blood alcohol concentration (BAC) is well-known to occur due
      to main factors such as the genetic polymorphism of the main alcohol metabolizing
      enzymes and the effect of blood. Few studies have substantially discussed the
      relationship between impaired CNS activities and BAC. In this study, focusing on
      the correlation of BAC, we investigated the acute effects of alcohol intake on
      cognitive performance in humans by objective evaluation methods consisting of the
      attention-demanding cognitive tasks. Tasks were administered to ten healthy male
      volunteers before and after ingesting established amounts of alcohol. With
      increased BAC, we observed prolongation of reaction time performances and
      lowering of a coordination performance. From the results, we concluded that
      cognitive performance deteriorates with an increase of BAC. Additionally, the BAC
      threshold that causes significant impairment of cognitive performance was
      estimated to be approximately 50 mg/dl (ca. 10 mM).

PMID- 10952076
TI  - Arachidonate 5-lipoxygenase and cyclooxygenase metabolites from guinea pig
      eosinophils and macrophages.
AB  - To investigate the cellular sources of arachidonate metabolites during asthma, in
      vitro productions of thromboxane (TX) B2, prostaglandin (PG) D2, leukotriene (LT)
      B4 and cysteinyl (Cys) LTs from guinea pig eosinophils and macrophages
      simultaneously stimulated with the Ca ionophore A23187 were investigated.
      Eosinophils produced high levels of LTB4 and TXB2 and relatively low levels of
      CysLTs and PGD2. Although macrophages released abundant TXB2 and a little PGD2, 5
      lipoxygenase metabolites were below detectable levels. In conclusion, eosinophils
      produced both cyclooxygenase and 5-lipoxygenase metabolites, while arachidonate
      metabolism in the macrophages was almost completely inclined toward the
      cyclooxygenase pathway.

PMID- 10952077
TI  - Changes in seizure susceptibility to local anesthetics by repeated administration
      of cocaine and nomifensine but not GBR12935: possible involvement of
      noradrenergic system.
AB  - We examined cross-sensitization of cocaine and synthetic local anesthetics to
      their seizure susceptibility after repeated administration. Seizure
      susceptibility of procaine and lidocaine increased after the end of two days of
      treatment with a subconvulsive dose of cocaine. Acute treatment with nomifensine
      but not GBR12935, a specific inhibitor of the dopamine transporter, facilitated
      lidocaine-induced convulsion. Furthermore, daily treatment with nomifensine for
      two days enhanced lidocaine-induced convulsion. These results suggest the
      possible involvement of the brain noradrenergic system in the changes in seizure
      susceptibility after repeated administration of some local anesthetics.

PMID- 10952078
TI  - Effect of zaldaride maleate, an antidiarrheal compound, on 16,16-dimethyl
      prostaglandin E2-induced intestinal ion secretion in rats.
AB  - The effect of zaldaride, a calmodulin inhibitor, on 16,16-dimethyl prostaglandin
      E2 (dmPGE2)-induced intestinal ion secretion was investigated in rats. Zaldaride
      inhibited the dmPGE2-induced increase in water content in the colon, but not that
      in the small intestine. In the colonic mucosa, zaldaride attenuated the dmPGE2
      induced short-circuit current; however, it did not affect the forskolin or
      dibutyryl cAMP-induced effect. These results suggest that zaldaride inhibits
      dmPGE2-induced intestinal ion secretion by reducing the activity of
      Ca2+/calmodulin-dependent adenylate cyclase linked to a receptor, and the colon
      may be an important site in the action of zaldaride.

PMID- 10952079
TI  - Assessment of genotoxicity of dental antiseptics: ability of phenol, guaiacol, p
      phenolsulfonic acid, sodium hypochlorite, p-chlorophenol, m-cresol or
      formaldehyde to induce unscheduled DNA synthesis in cultured Syrian hamster
      embryo cells.
AB  - To assess the genotoxicity of seven dental antiseptics, the ability of these
      agents to induce unscheduled DNA synthesis (UDS) was examined using Syrian
      hamster embryo (SHE) cells. Treatment of SHE cells with phenol or formaldehyde
      induced UDS in a concentration-dependent manner as determined by direct
      scintillation counting of [3H]thymidine incorporated into DNA during repair
      synthesis. Guaiacol or m-cresol induced UDS only in the presence of exogenous
      metabolic activation. p-Phenolsulfonic acid, sodium hypochlorite and p
      chlorophenol failed to induce UDS in the presence or absence of exogenous
      metabolic activation. Our results suggest that phenol, guaiacol, m-cresol and
      formaldehyde are genotoxic to mammalian cells.

PMID- 10952080
TI  - Ca2+-independent phospholipase A2 inhibitor impairs spatial memory of mice.
AB  - Pharmacological blockade of Ca2+-independent phospholipase A2 (PLA2) is reported
      to disintegrate hippocampal synaptic plasticity, which is thought to be the
      cellular mechanism underlying learning and memory. Therefore, we investigated the
      effect of the Ca2+-independent PLA2 inhibitor bromoenol lactone (BEL) on
      spontaneous alteration behaviors of mice. When 3 nmol BEL was
      intracerebroventricularly injected 30 min prior to the test, the mice showed a
      poor alternation ratio, compared with control animals. The data suggest that Ca2+
      independent PLA2 activity is required for spatial memory.

PMID- 10952081
TI  - Five decades of antihypertensive treatment: the unresolved issues.
AB  - The first effective antihypertensive treatment became available in the 1950s but
      the early drugs caused intolerable side effects. Drugs with a better side-effect
      profile became available in the 1960s, and their utility was soon subjected to
      rigorous clinical trials. In the 1970s, the availability of these drugs opened
      the door for outcome studies. Most of the results reported in the 1970s and 1980s
      were rather impressive. Antihypertensive treatment reduced mortality in severe
      and mild hypertension, in hypertension of the elderly, and in patients with
      advanced complications of hypertension. A large number of 'hard end point'
      (mortality and morbidity) trials were organized in the last decade of the 20th
      century. Most compare the merits of new antihypertensive agents (angiotensin
      converting enzyme inhibitor, calcium channel blocker, angiotensin II receptor
      blocker) versus an older (beta-blocker or diuretic) drug. These trials are rooted
      in the fact that blood pressure lowering does not equally affect all
      complications of hypertension. Particularly bothersome is the fact that treatment
      decreases stroke but fails to substantially reduce coronary events. These
      variations in treatment outcomes may reflect the multifactorial pathophysiology
      of hypertension: essential hypertension is frequently associated with pressure
      independent coronary risk factors, and the target organ status of a patient (left
      ventricular hypertrophy, renal dysfunction) greatly affects their prognosis.
      These new trials investigate whether the mechanism by which a drug decreases the
      pressure and how it affects various risk factors are of clinical relevance. The
      practice of medicine in hypertension is evidence bound. Historically, only when
      the superiority of the treatment had been convincingly shown did physicians alter
      practice patterns. The effects of systolic blood pressure lowering and of
      treating mild diastolic hypertension in younger patients have not been
      sufficiently investigated. Lowering of the systolic blood pressure and treating
      patients with mild hypertension might have major beneficial effects on public
      health. We need new studies in this area in order to improve clinical practice in
      hypertension.

PMID- 10952082
TI  - Does the benefit of antihypertensive treatment outweigh the risk in very elderly
      hypertensive patients?
AB  - The risk of hypertension and the benefits of antihypertensive treatment are well
      established in older patients aged up to 80 years. For people aged 85 and over,
      data are scarce and conflicting. A positive association between blood pressure
      and survival has been found in several cohort studies; this relationship held
      true after adjustment for many factors in some studies, but disappeared after
      adjustment for indicators of poor health in others. In randomized trials, the
      benefit of antihypertensive treatment was demonstrated in the Systolic
      Hypertension in the Elderly Program (SHEP) study, but it declined with age and
      was not observable after 80 years in the European Working Party on High Blood
      Pressure in the Elderly (EWPHE) study. The SYSTolic hypertension in elderly in
      EURope Trial (SYST-EUR) study evidenced a benefit on cardiovascular morbidity but
      not on mortality. People who reach a very old age share some characteristics that
      make them different from those '60 (or 65) and over' and justify special studies
      which are currently in progress. In the meantime, any treatment decision can only
      rely on extrapolations moderated by common sense, but the already demonstrated
      favorable results on morbidity argue against a threshold beyond which
      hypertension should not be treated.

PMID- 10952083
TI  - Is systolic pressure a better target for antihypertensive treatment than
      diastolic pressure?
AB  - BACKGROUND: Diastolic blood pressure has been evaluated in different prospective
      cohort studies and in pharmacological intervention trials, which have shown the
      increased risk of cardiovascular events in hypertensive patients and the benefits
      of antihypertensive therapy. AIMS: To show that systolic blood pressure is at
      least as important as, or even more important than, diastolic blood pressure as a
      risk factor for cardiovascular complications. METHODS: Review of medical
      literature. RESULTS: Large epidemiological trials such as the Multiple Risk
      Factors Intervention Trial (MRFIT) and the Framingham study have shown that
      systolic blood pressure is an independent, continuous and modifiable risk for all
      cardiovascular complications, and in elderly subjects isolated systolic
      hypertension is the most frequent form of hypertension. In elderly subjects the
      increased stiffness of large arteries is responsible for the early reflection of
      pulse wave and for the decrease in diastolic blood pressure due to reduced recoil
      of large arteries. This is summarized in the increase in pulse pressure, which is
      directly related to the risk of cardiovascular complications. Three large
      intervention trials in elderly patients with isolated systolic hypertension have
      shown the relevant cardiovascular benefit of pharmacological reduction of
      elevated systolic blood pressure and normal diastolic values: the cardiovascular
      benefit is similar to that found in the general hypertensive population and in
      elderly patients with systolic-diastolic hypertension. CONCLUSION: Systolic blood
      pressure represents an important risk factor for cardiovascular events which can
      be prevented or reduced with pharmacological treatment.

PMID- 10952084
TI  - Regression of left ventricular hypertrophy: do antihypertensive classes differ?
AB  - Left ventricular hypertrophy (LVH) is now recognized as a major risk factor for
      cardiac morbidity and mortality, a component of which is independent of
      associated coronary heart disease. The mechanisms that underlie this risk are
      increasingly understood and include disturbances in cardiac electrophysiology,
      coronary perfusion and myocardial contractile function. Recognition that
      regression of LVH confers prognostic benefit has focused attention on developing
      optimal treatments to achieve this. Early studies suggested that regression is
      achievable using a variety of antihypertensive classes. Many of these early
      studies were either poorly controlled or of inadequate size to provide reliable
      comparisons between different agents. Subsequently a number of meta-analyses,
      based on selections of these early studies, have been published. More recently, a
      number of well-designed prospective clinical trials have been published or are
      under way. In summary of these results: (1) the extent of regression seen in
      early studies appears to be greater than that reported in recent large, well
      designed trials, possibly due to regression to the mean in small studies with
      high coefficients of variation for echocardiographically measured left
      ventricular (LV) mass index; (2) meta-analyses based on these early studies tend
      to suggest that angiotensin-converting enzyme (ACE) inhibitors may be most
      effective in regressing LVH; (3) recent larger trials [Treatment Of Mild
      Hypertension Study (TOMHS), the Veterans Administration (VA) study, and Left
      ventricular hypertrophy: Indapamide Versus Enalapril (LIVE)] indicate that
      angiotensin-converting enzyme inhibitors and diuretics maintain a strong place in
      achieving regression of LVH. Long-term studies currently under way should help
      clarify the prognostic benefit associated with regression of LVH using
      antihypertensive therapy. Future work will focus on whether regression of LV mass
      is associated with reversal of the underlying pathophysiology of hypertrophy and,
      ultimately, whether prevention of LVH should be the optimal goal.

PMID- 10952085
TI  - A cardioprotective approach to the management of hypertension.
AB  - In view of the currently inadequate control of hypertension, multiple guidelines
      have recently been published to help improve the management of this increasingly
      common condition. In most regards these guidelines are in agreement, in
      particular as to the need for overall cardiovascular risk assessment, the
      selection of appropriate initial therapy, the need for long-acting formulations,
      and for a diuretic as part of most regimens.

PMID- 10952086
TI  - Extracellular Ca2+ sensitivity of mGluR1alpha induces an increase in the basal
      cAMP level by direct coupling with Gs protein in transfected CHO cells.
AB  - We previously reported that the metabotropic glutamate receptor R1alpha
      (mGluR1alpha) can be activated not only by applying glutamate but also by raising
      extracellular Ca2+ (Ca2+o) concentration, and that the constant stimulation by
      Ca2+o causes morphological change of transfected Chinese Hamster Ovary (CHO)
      cells (Kubo Y Miyashita T and Murata Y (1998) Science 279, 1722-1725). The
      physiological role of the Ca2+o-sensing function of mGluR1alpha, however, is not
      fully clear yet, especially because Ca2+ is constitutively present in the
      extracellular space unlike other neurotransmitters. In this work, we aimed to
      elucidate the physiological significance of the Ca2+o-sensing function of
      mGluR1alpha. The effect of mGluR1alpha activation by Ca2+o on the morphological
      change of CHO cells was mimicked by forskolin. The effect of mGluR1alpha
      activation on the morphological change was suppressed by the inhibitors of
      adenylate cyclase, protein kinase A (PKA) and MAP kinase kinase (MAPKK), and the
      effect of forskolin was also decreased by the inhibitors of PKA and MAPKK. These
      results demonstrate the involvement of cAMP, PKA, MAPKK, MAPK pathway in the
      morphological change. We actually confirmed that the Ca2+o stimulation of
      mGluR1alpha increased the basal cAMP level of transfected CHO cells. This
      increase in cAMP was observed even when only the membrane fraction of mGluR1alpha
      transfected CHO cells were used, and the increase was inhibited by anti-Gs alpha
      antibody. Taken together, we concluded that the Ca2+o-sensing function of
      mGluR1alpha and the continuous stimulation by Ca2+o caused the increase in the
      basal cAMP level by direct coupling with Gs, and triggered the subsequent
      activation of PKA, MAPKK, and MAPK cascade which resulted in the morphological
      change of transfected CHO cells.

PMID- 10952088
TI  - Bacterial expression of G-protein-coupled receptors: prediction of expression
      levels from sequence.
AB  - Eleven G-protein-coupled receptors were expressed in Escherichia coli as fusion
      proteins with N-terminal glutathione-S-transferase and a C-terminal (His)6 tag.
      Expression levels varied between 0.1% and 10% of the total cellular protein. Low
      expression levels, as quantified by analytical nickel chelating chromatography,
      coincided with a toxic effect of protein expression. Multiple linear regression
      analysis was used to establish a correlation between the occurrence of positively
      charged amino acid residues in the loop regions and the expression level. Indeed,
      44% of the variation in expression levels could be attributed to the positive
      charge content. Consequently, this sequence feature is the major determinant of
      expression level. Our results were supported by two mutations where positive
      charges were introduced into loop regions of two low-expressing receptors: As
      predicted, these mutations led to a considerably higher expression. A similar
      mutation of an olfactory receptor described previously increased expression
      approximately 100-fold and further supports our model. The data are discussed in
      the context of the "positive inside rule".

PMID- 10952087
TI  - The human ET(B) endothelin receptor heterologously produced in the methylotrophic
      yeast Pichia pastoris shows high-affinity binding and induction of stacked
      membranes.
AB  - The human endothelin B receptor (ET(B) receptor) was produced in the
      methylotrophic yeast Pichia pastoris under transcriptional control of the highly
      inducible alcohol oxidase 1 (AOX1) gene promoter. In the expression plasmids
      pPIC9KFlagET(B)Bio and pPIC9KFlag deltaGPET(B)Bio the ET(B) receptor coding
      region was fused in frame to the Saccharomyces cerevisiae alpha-factor
      prepropeptide and the FLAG-tag. In both constructs, the receptor was also fused
      to a biotinylation domain. Additionally, in pPIC9KFlag deltaGPET(B)Bio the
      putative N-glycosylation site and a protease site have been deleted by site
      directed mutagenesis. Crude membranes prepared from recombinant P. pastoris
      revealed specific and saturable binding of [125I]ET-1 with a K(D) of about 42 pM.
      Receptor levels of 60 pmol/mg and 35 pmol/mg for the Flag deltaGPET(B)Bio and the
      FlagET(B)Bio construct, respectively, were determined. The pharmacological
      profile for ET-1, ET-2 and ET-3 were as expected for a subtype B endothelin (ET)
      receptor. Immunoblot analysis showed an apparent molecular mass of 55 kDa for the
      Kex2-processed and about 74 kDa for the Kex2-unprocessed receptor. Contrary to
      the Flag deltaGPET(B)Bio construct, the FlagET(B)Bio construct was not correctly
      processed by the internal Kex2 endopeptidase. As was detected by ultrastructural
      analysis of recombinant yeast cells, high-level production of the receptor
      resulted in the formation of stacked membranes.

PMID- 10952089
TI  - A novel computational method for predicting the transmembrane structure of G
      protein coupled receptors: application to human C5aR and C3aR.
AB  - A novel algorithm was applied to the sequences of bacteriorhodopsin (BRh), of
      rhodopsin (Rh), and of the two human anaphylatoxin receptors, C5a-receptor
      (hC5aR) and C3a-receptor (hC3aR), that predicts their transmembrane domains (TMD)
      according to energy criteria alone, on the basis of their sequences and a
      template structure for each. Two consecutive criteria were applied for the
      predictions: the first is hydrophobicity of a sequence of residues, which
      determines the candidate stretches of residues that form one of the transmembrane
      helices. The second criterion is an energy function composed of inter residue
      contact energies, of hydrophobic contributions due to membrane exposure and of
      the interactions of a few residues with the phospholipid head groups. The
      sequence of candidate residues for each helix is longer than that of the
      template, and is finally determined by threading each of the candidate stretches
      on each of the template helices and evaluating the energy for all possible
      configurations. Contact energies between residues were taken from a database
      (Miyazawa S and Jernigan RL (1996) J Mol Biol 256 623-44). The algorithm predicts
      well the TMD structure of BRh based on its own template, and the TMD structure of
      Rh conforms well with the model of Baldwin et al (Baldwin JM Schertler GFX and
      Unger VM (1997) J Biol Chem 272 144-64). Results for the construction of the TMD
      of hC5aR and hC3aR were compared, employing the template structure of Rh. Most of
      the results for these receptors are in accord with alignments and with mutation
      experiments on hC5aR and hC3aR. The predictions may serve as a basis for future
      mutagenesis experiments of these receptors.

PMID- 10952090
TI  - Stable expression of human homomeric and heteromeric AMPA receptor subunits in
      HEK293 cells.
AB  - Human homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA)-type glutamate receptors (GluRs) were stably expressed
      in HEK293 cells with cDNAs encoding the flip splice variant of GluR1, GluR2,
      GluR3, GluR4 subunit, and the GluR1/GluR2, GluR3/GluR2, and GluR4/GluR2
      combination. The lethal combination of GluR2 and GluR4 subunits was found in high
      expression levels of both receptors. The AMPA-evoked current voltage
      relationships demonstrated the functional channel properties, such as a double
      rectification in GluR1, GluR3, and GluR4 receptors, and a linear relation in
      receptors assembled from GluR2 alone and coexpression of GluR2 with the other
      subunits. All the transfectants exhibited higher selectivity for AMPA than
      glutamate in dose-dependent current responses. [3H]AMPA binding revealed that the
      homomeric and heteromeric receptors displayed a single binding site in Scatchard
      analysis, with dissociation constant (Kd) values in the range of 14.5-49.3 nM.
      The Bmax values were in the range of 0.57-7.66 pmol/mg protein. The ligand
      displacement potency for [3H]AMPA binding was CNQX > glutamate > NS257 in all of
      the transfectants. These results suggest that stable transformants expressing
      human homomeric and heteromeric AMPA receptors will be useful tools to define
      selectivity and potential site of action for AMPA receptor modulators.

PMID- 10952091
TI  - GABA(A) receptor modulation in rat cerebellum granule cells.
AB  - The inhibitory GABA(A) receptor is a key element in determining the pattern of
      nerve cell electrical activity. Thus, modulation of its function is of paramount
      impact in shaping neuronal functional activity under physiological and
      pathological conditions. This applies to cerebellar granule neurons as to all the
      other neurons in the brain. The culture of cerebellar granules from newborn rats
      is a convenient means by which to approach these cells for electrophysiological
      studies provided that they maintain, as far as GABA(A) receptors are concerned,
      the same characteristics as in situ. Thus, the regulation of GABA(A) receptor
      activity in these neurons has been studied by the patch-clamp technique, both in
      the whole-cell and outside-out configuration. An obvious first level of control
      of such receptors' activity is their desensitization under continued agonist
      application, with biphasic kinetics. The data do not allow one to conclude
      whether one is dealing with two different populations of receptors or with a
      single population with two desensitization phases; although the presence of two
      GABA(A) receptor populations is suggested by a host of observations. The granule
      cell GABA(A) receptors are modulated by changes in extracellular pH with lower pH
      resulting in an enhanced receptor activity. They display, under the conditions of
      whole-cell recording, a run-down phenomenon which is most probably due to a
      tyrosine phosphatase activity which is in turn under control by a protein serine
      kinase. Thus, in situ tyrosine phosphorylation is a key element in determining
      the efficiency of GABA mediated inhibition. Activation of protein kinase A or
      protein kinase G (PKG) down-regulates GABA(A) receptors' activity. This last
      event is involved in the depression of those receptors' activity by L-arginine
      via the production of nitric oxide. In addition, the activity of calmodulin
      activated adenylate cyclase I is controlled by GABA(B) receptors. Dendritic
      GABA(A) receptor activity is partially blocked by previous activation of N-methyl
      D-aspartate (NMDA) receptors via calcineurin mediated
      dephosphorylation/activation of protein tyrosine phosphatase and concomitant
      production of nitric oxide and PKG activation. The site phosphorylated by PKG is
      evidently not available for calcineurin-mediated serine dephosphorylation, due to
      calcineurin-specific membrane localization in respect of the GABA(A) receptor.
      Overall, a complex network of biochemical signals appear to keep granule cells
      GABA(A) receptors under a fine balance between up- and down-regulatory
      mechanisms. The overall data appear also to indicate the presence of two GABA(A)
      receptor populations: a dendritic one which can be modulated by Ca++ entering via
      NMDA receptors and a cell body one. The two populations are probably different in
      terms of desensitization kinetics and benzodiazepine sensitivity.

PMID- 10952092
TI  - Publication bias is a scientific problem with adverse ethical outcomes: the case
      for a section for null results.

PMID- 10952093
TI  - Brassica vegetable consumption shifts estrogen metabolism in healthy
      postmenopausal women.
AB  - Previous studies suggest that the estrogen metabolite 16alpha-hydroxyestrone acts
      as a breast tumor promoter. The alternative product of estrogen metabolism, 2
      hydroxyestrone, does not exhibit estrogenic properties in breast tissue, and
      lower values of the ratio 2-hydroxyestrone:16alpha-hydroxyestrone (2:16) in urine
      may be an endocrine biomarker for greater breast cancer risk. Vegetables of the
      Brassica genus, such as broccoli, contain a phytochemical, which may shift
      estrogen metabolism and increase the 2:16 ratio. Adding 500 g/day of broccoli to
      a standard diet shifts 2:16 values upward in humans; however, it is unknown as to
      whether healthy women are able to consume a sufficient quantity of Brassica to
      affect breast cancer risk through this mechanism. In this study, 34 healthy
      postmenopausal women participated in an intensive intervention designed to
      facilitate the addition of Brassica to the daily diet. The diet was measured by
      repeated 24-h recall, and estrogen metabolites were measured by enzyme
      immunoassay in 24-h urine samples. In a crude analysis, there was a
      nonsignificant increase in the urinary 2:16 ratio associated with greater
      Brassica consumption. With adjustment for other dietary parameters, Brassica
      vegetable consumption was associated with a statistically significant increase in
      2:16 values, such that for each 10-g/day increase in Brassica consumption, there
      was an increase in the 2:16 ratio of 0.08 (95% confidence interval, 0.02-0.15).
      To the extent that the 2:16 ratio, as measured in urine, is associated with
      breast cancer risk, future research should consider Brassica vegetable
      consumption as a potentially effective and acceptable dietary strategy to prevent
      breast cancer.

PMID- 10952094
TI  - Soy consumption alters endogenous estrogen metabolism in postmenopausal women.
AB  - Isoflavones are soy phytoestrogens that have been suggested to be
      anticarcinogenic. Our previous study in premenopausal women suggested that the
      mechanisms by which isoflavones exert cancer-preventive effects may involve
      modulation of estrogen metabolism away from production of potentially
      carcinogenic metabolites [16alpha-(OH) estrone, 4-(OH) estrone, and 4-(OH)
      estradiol] (X. Xu et al., Cancer Epidemiol. Biomark. Prev., 7: 1101-1108, 1998).
      To further evaluate this hypothesis, a randomized, cross-over soy isoflavone
      feeding study was performed in 18 healthy postmenopausal women. The study
      consisted of three diet periods, each separated by a washout of approximately 3
      weeks. Each diet period lasted for 93 days, during which subjects consumed their
      habitual diets supplemented with soy protein isolate providing 0.1 (control), 1,
      or 2 mg isoflavones/kg body weight/day (7.1 +/- 1.1, 65 +/- 11, or 132 +/- 22
      mg/day). A 72-h urine sample was collected 3 days before the study (baseline) and
      days 91-93 of each diet period. Urine samples were analyzed for 10 phytoestrogens
      and 15 endogenous estrogens and their metabolites by a capillary gas
      chromatography-mass spectrometry method. Compared with the soy-free baseline and
      very low isoflavone control diet, consumption of 65 mg isoflavones increased the
      urinary 2/16alpha-(OH) estrone ratio, and consumption of 65 or 132 mg isoflavones
      decreased excretion of 4-(OH) estrone. When compared with baseline values,
      consumption of all three soy diets increased the ratio of 2/4-(OH) estrogens and
      decreased the ratio of genotoxic: total estrogens. These data suggest that both
      isoflavones and other soy constituents may exert cancer-preventive effects in
      postmenopausal women by altering estrogen metabolism away from genotoxic
      metabolites toward inactive metabolites.

PMID- 10952095
TI  - Modulation of human glutathione S-transferases by botanically defined vegetable
      diets.
AB  - Glutathione S-transferases (GSTs) conjugate activated xenobiotics with
      glutathione; thus, GST induction may improve detoxification and excretion of
      potentially harmful compounds. Using a randomized cross-over design, we tested
      the hypothesis that, in humans, serum GST-alpha concentration (GST-alpha) and GST
      activity increase with vegetable consumption and that this effect is GSTM1
      genotype dependent. Twenty-one men (10 GSTM1-null and 11 GSTM1+) and 22 women (15
      GSTM1-null and 7 GSTM1+), nonsmokers, 20-40 years of age and not on medications,
      ate four 6-day controlled diets: basal (vegetable-free), and basal supplemented
      with three botanically defined groups of vegetables (i.e., brassica, allium, and
      apiaceous). Fasting blood samples, collected on the last 2 days of each feeding
      period, were analyzed for GST-alpha, serum GST activity [against 1-chloro-2,4
      dinitrobenzene (CDNB) and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)] and
      peripheral-lymphocyte GST-mu activity (against trans-stilbene oxide). The
      brassica, but not allium or apiaceous, vegetable diets (relative to the basal
      diet) increased GST-alpha by 26% (P = 0.005) and GST (NBD-Cl) activity by 7% (P =
      0.02) in the GSTM1-null individuals, particularly the women. Apiaceous vegetable
      supplementation decreased GST-alpha in the GSTM1+ men (P = 0.03). Among the
      GSTM1+ women, both brassica and the allium diets increased GST-mu activity by 18%
      (P = 0.02) and 26% (P = 0.001), respectively. The vegetable diets had no effect
      on GST (CDNB) activity, irrespective of GSTM1 genotype or sex. These results
      demonstrate that GSTM1 genotype has a significant effect on GST responses to diet
      and that brassica vegetables are most effective at inducing GST-alpha, whereas
      both brassica and allium vegetables induce GST-mu. GST responses were more
      pronounced in women than men, but it is not clear from this study whether this is
      a dose-per-body-weight or a sex-specific effect.

PMID- 10952096
TI  - Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control
      study.
AB  - The evidence for a protective effect of vegetables, fruits, and legumes against
      prostate cancer is weak and inconsistent. We examined the relationship of these
      food groups and their constituent foods to prostate cancer risk in a multicenter
      case-control study of African-American, white, Japanese, and Chinese men. Cases
      (n = 1619) with histologically confirmed prostate cancer were identified through
      the population-based tumor registries of Hawaii, San Francisco, and Los Angeles
      in the United States and British Columbia and Ontario in Canada. Controls (n =
      1618) were frequency-matched to cases on ethnicity, age, and region of residence
      of the case, in a ratio of approximately 1:1. Dietary and other information was
      collected by in-person home interview; a blood sample was obtained from control
      subjects for prostate-specific antigen determination. Odds ratios (OR) were
      estimated using logistic regression, adjusting for age, geographic location,
      education, calories, and when indicated, ethnicity. Intake of legumes (whether
      total legumes, soyfoods specifically, or other legumes) was inversely related to
      prostate cancer (OR for highest relative to lowest quintile for total legumes =
      0.62; P for trend = 0.0002); results were similar when restricted to prostate
      specific antigen-normal controls or to advanced cases. Intakes of yellow-orange
      and cruciferous vegetables were also inversely related to prostate cancer,
      especially for advanced cases, among whom the highest quintile OR for yellow
      orange vegetables = 0.67 (P for trend = 0.01) and the highest quintile OR for
      cruciferous vegetables = 0.61 (P for trend = 0.006). Intake of tomatoes and of
      fruits was not related to risk. Findings were generally consistent across ethnic
      groups. These results suggest that legumes (not limited to soy products) and
      certain categories of vegetables may protect against prostate cancer.

PMID- 10952097
TI  - Why are the majority of hereditary cases of early-onset breast cancer sporadic? A
      simulation study.
AB  - Population-based studies, including those of Ashkenazi Jews, have observed that
      at least 50% of women with early-onset breast cancer who carry a germ line
      mutation in BRCA1 or BRCA2 do not report a family history of the disease. That
      is, the majority of "hereditary" cases are "sporadic." Furthermore, the great
      majority of "familial breast cancers" are not hereditary. We conducted a
      simulation study to evaluate the probability that a woman with early-onset breast
      cancer is a mutation carrier, given the number of affected relatives, for a range
      of plausible values of allele frequency (0.001-0.01), and increased risk in
      mutation carriers (5-20, equivalent to cumulative risks to age 70 of 25-70%,
      respectively, for Australian women). Families consisted of a case proband and her
      mother, sisters, and maternal and paternal grandmothers, and aunts. The numbers
      of sisters and aunts were generated according to Poisson distributions, and ages
      were assigned according to a Weibull distribution. The simulated distributions of
      family history and of the prevalence of mutation carriers among case probands
      were in general similar to those observed in population-based studies, although
      there was a suggestion of heterogeneity of breast cancer risk in mutation
      carriers. As is being observed empirically in population-based samples, a family
      history of breast cancer was not a strong predictor of mutation status; each
      affected female relative increased the risk of being a mutation carrier by only 2
      to 3-fold. The probability of being a mutation carrier was generally low, except
      in families with extreme histories of breast cancer.

PMID- 10952098
TI  - Case-control study of colon and rectal cancers and chlorination by-products in
      treated water.
AB  - This population-based case-control study was conducted in southern Ontario,
      Canada from 1992 to 1994 to assess the relationship between chlorination by
      products in public water supplies and cancers of the colon and rectum. Interviews
      providing residence and water source histories were completed by 76% of eligible
      cancer cases and 72% of eligible controls. Supplemental data from municipal water
      supplies were used to estimate individual exposure to water source, chlorination
      status, and by-product levels as represented by trihalomethanes (THMs) during the
      40-year period before the interview. The analyses included 767 colon cases, 661
      rectal cases, and 1545 controls with exposure information for at least 30 of
      these years (75% of subjects with completed interviews). Among males, colon
      cancer risk was associated with cumulative exposure to THMs, duration of exposure
      to chlorinated surface water, and duration of exposure to a THM level > or = 50
      microg/liter and 75 microg/liter. Males exposed to chlorinated surface water for
      35-40 years had an increased risk of colon cancer compared with those exposed for
      < 10 years (odds ratio, 1.53; 95% confidence interval, 1.13-2.09). Males exposed
      to an estimated THM level of 75 microg/liter for > or = 35 years had double the
      risk of those exposed for < 10 years (odds ratio, 2.10; 95% confidence interval,
      1.21-3.66). In contrast, these relationships were not observed among females. No
      relationship was observed between rectal cancer risk and any of the measures of
      exposure to chlorination by-products. The results of this study should be
      interpreted with caution because they are only partially congruent with the
      limited amount of literature addressing this issue.

PMID- 10952099
TI  - Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part
      by increasing apoptosis during tumor initiation.
AB  - There is epidemiological, clinical, and experimental evidence that dietary fish
      oil, containing n-3 polyunsaturated fatty acids, protects against colon tumor
      development. However, its effects on colonocytes in vivo remain poorly
      understood. Therefore, we investigated the ability of fish oil to modulate
      colonic methylation-induced DNA damage, repair, and deletion. Sprague Dawley rats
      were provided with complete diets containing either corn oil or fish oil (15% by
      weight). Animals were injected with azoxymethane, and the distal colon was
      removed 3, 6, 9, or 12 h later. Targeted apoptosis and DNA damage were assessed
      by cell position within the crypt using the terminal deoxynucleotidyl transferase
      mediated nick end labeling assay and quantitative immunohistochemical analysis of
      O6-methylguanine adducts, respectively. Localization and expression of the alkyl
      group acceptor, O6-methylguanine-DNA-methyltransferase, was also determined.
      Lower levels of adducts were detected at 6, 9, and 12 h in fish oil- versus corn
      oil-fed animals (P < 0.05). In addition, fish oil supplementation had the
      greatest effect on apoptosis in the top one-third of the crypt, increasing the
      apoptotic index compared with corn oil-fed rats (P < 0.05). In the top one-third
      of the crypt, fish oil feeding caused an incremental stimulation of apoptosis as
      adduct level increased. In contrast, a negative correlation between apoptosis and
      adduct incidence occurred with corn oil feeding (P < 0.05). Diet had no main
      effect (all tertiles combined) on O6-methylguanine-DNA-methyltransferase
      expression over the time frame of the experiment. The enhancement of targeted
      apoptosis combined with the reduced formation of O6-methylguanine adducts may
      account, in part, for the observed protective effect of n-3 polyunsaturated fatty
      acids against experimentally induced colon cancer.

PMID- 10952100
TI  - Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.
AB  - Glutathione S-transferase (GST) polymorphism may contribute to the individual
      variability in detoxifying lung carcinogens. This effect might be particularly
      relevant at low-level exposure to environmental carcinogens, such as in
      nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case
      control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls
      from eight countries. Information on environmental exposures was obtained through
      a personal interview. The presence of GSTM1 and GSTT1 genes was determined using
      multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B
      polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null)
      individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval
      (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with
      squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with
      adenocarcinomas. It was also elevated in individuals with long-term exposure to
      indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived
      in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to
      occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed
      to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests
      that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in
      smokers. It does not seem to interact with ETS exposure, although we cannot
      exclude that it does in association with exposure to other specific environmental
      carcinogens.

PMID- 10952101
TI  - Risk of childhood leukemia and parental self-reported occupational exposure to
      chemicals, dusts, and fumes: results from pooled analyses of German population
      based case-control studies.
AB  - A recent large-scale United States study reported an association between parental
      exposure to hydrocarbons at work and the risk of childhood leukemia. Parental
      occupational exposure to different chemicals and industrial dusts or fumes also
      was assessed in three German case-control studies that were conducted from 1992
      1997. The design and methods of exposure assessment were similar for these
      studies; therefore, they were pooled for this analysis. In total, these three
      studies involved 1138 cases of acute lymphocytic leukemia (ALL) and 2962
      controls. We found that maternal exposure to paints or lacquers during the
      preconception period (odds ratio, 1.6; 95% confidence interval, 1.1-2.4) and
      during the index pregnancy (odds ratio, 2.0; 95% confidence interval, 1.2-3.3)
      was related to an increased risk of childhood ALL. Whereas our findings for
      exposure to paints or lacquers confirmed observations from the United States
      study, we failed to confirm associations between risk of ALL and maternal
      exposure to solvents and parental exposure to plastic materials. Our studies
      provide some evidence that parental occupational exposure to certain substances
      may be associated with cancer risk in offspring; however, more specific studies
      are needed to identify such substances and the doses that may be hazardous.

PMID- 10952102
TI  - Genetic variant of luteinizing hormone and risk of breast cancer in older women.
AB  - A genetic variant of luteinizing hormone (LH) characterized by two point
      mutations in codons 8 (TGG-->CGG) and 15 (ATC-->ACC) of the LH beta-subunit gene
      has been described recently. As compared with wild-type LH, the variant LH
      appears to have higher in vitro bioactivity but a shortened circulatory half
      life, and it has been reported to affect circulating levels of sex hormones. Our
      purpose was to determine whether the variant form of LH is associated with an
      altered risk of breast cancer. This hypothesis was addressed in a case-control
      study nested within a prospective cohort that included 270 cases of breast cancer
      and twice as many matching control subjects. The study was limited to subjects
      diagnosed at age 50 years or older. The LH status was determined by the
      combination of two immunofluorometric assays of serum using monoclonal
      antibodies. Frequency of the variant LH was similar in breast cancer cases and
      controls (11.5% versus 10.7%). In conditional regression models, the presence of
      the variant LH was not associated with a considerable increase of breast cancer
      risk (odds ratio, 1.07; 95% confidence interval, 0.68-1.69). Adjustment for
      potential confounders did not notably change the risk estimate (odds ratio, 1.11;
      95% confidence interval, 0.69-1.78). These observations do not appear to support
      the hypothesis that this particular variant of LH is associated with altered risk
      of breast cancer diagnosed at age 50 years and older.

PMID- 10952103
TI  - Association of an ERCC1 polymorphism with adult-onset glioma.
AB  - Gliomas include several histologically distinct types of tumors whose molecular
      profiles suggest different etiologies. Because the ERCC1 protein is essential for
      nucleotide excision repair and influences genomic instability, polymorphisms in
      ERCC1 may play a role in human tumors. We determined the presence of the A versus
      C polymorphism at nucleotide 8092 of ERCC1 using a single-strand conformational
      polymorphism assay and DNA sequencing in adults with glioma and controls from a
      population-based study. Among 318 alleles from 159 controls, 27% (86) were A and
      73% were C. Prevalences of the CC genotype were 51% (81 of 159), 48% (30 of 62),
      63% (20 of 32), and 82% (23 of 28) for controls and subjects with glioblastoma
      multiforme, astrocytoma, and oligoastrocytoma, respectively (Fisher's exact P =
      0.009). The age-adjusted odds ratio for genotype CC in all cases versus controls
      was 1.4 (95% confidence interval, 0.9-2.3), whereas that for subjects with
      oligoastrocytoma versus controls was 4.6 (95% confidence interval, 1.6-13.2). The
      median age at diagnosis was 46 years for glioma patients with the CC genotype
      compared with 54 years for patients with the AA or AC genotype (P = 0.04). This
      is the first study to report a significant association of a polymorphism in ERCC1
      with the risk of brain tumors. This A/C polymorphism, which may affect mRNA
      stability for ERCC1, also results in an amino acid substitution of lysine to
      glutamine in a recently described nucleolar protein (ASE-1) and T-cell receptor
      complex subunit CD3epsilon-associated signal transducer (CAST). This finding, if
      confirmed in other series, may provide a foundation on which to study novel
      mechanisms of carcinogenesis in subsets of glioma.

PMID- 10952104
TI  - Genomic DNA hypomethylation, a characteristic of most cancers, is present in
      peripheral leukocytes of individuals who are homozygous for the C677T
      polymorphism in the methylenetetrahydrofolate reductase gene.
AB  - DNA methylation is an epigenetic feature of DNA that influences cellular
      development and function, and aberrations of DNA methylation are a candidate
      mechanism for the development of cancer. Methylenetetrahydrofolate reductase
      (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for
      methionine synthesis and the precursor of S-adenosylmethionine. S
      adenosylmethionine is the universal methyl donor for methylation reactions,
      including that of DNA methylation. In the present study, we investigated whether
      a common C677T mutation in the MTHFR gene, which results in reduced enzyme
      activity in vitro, affects genomic DNA methylation. We selected 9 subjects
      homozygous for the wild-type MTHFR and 10 subjects homozygous for the mutation
      (T/T). Genomic DNA methylation was determined by an established enzymatic assay
      that measures the capacity of DNA to accept methyl groups in vitro, which is
      inversely related to endogenous methylation. DNA from subjects with the T/T MTHFR
      genotype had a significantly higher methyl group acceptance capacity (12,615 +/-
      1836 dpm/2 microg of DNA) compared with wild-type MTHFR (7843 +/- 1043 dpm/2
      microg of DNA; P < 0.05), indicating DNA hypomethylation in the T/T genotype.
      Furthermore, DNA methylation was directly and significantly related to RBC folate
      concentrations in persons with the T/T genotype, but not in those with wild-type
      MTHFR. These data are consistent with prior observations, which suggest that the
      T/T genotype is associated with impaired MTHFR activity in vivo and that the
      cellular impact of this impairment is determined, in part, by folate status. The
      relationship of genomic DNA hypomethylation in persons with the T/T MTHFR
      genotype to the development of cancer remains to be defined.

PMID- 10952105
TI  - A prospective study of cytochrome P450 1A1 polymorphisms and colorectal cancer
      risk in men.

PMID- 10952106
TI  - Articular cartilage biomechanics: theoretical models, material properties, and
      biosynthetic response.
AB  - Articular cartilage has unique material properties that enable the cartilage to
      perform its physiological functions over a lifetime and under a wide range of
      loading conditions. Numerous studies have investigated the relationship between
      cartilage properties and composition/structure. For cartilage transplantation and
      regeneration, it is necessary to know how cartilage maintains its functionality
      and how cartilage responds to the ever-changing mechanical environment. In this
      review, we discuss theoretical and experimental studies on the behavior of
      articular cartilage to load. In the first part, the composition and structure of
      articular cartilage is presented. In the second part, theoretical models of the
      mechanical behavior of cartilage, experimental methods for the determination of
      cartilage properties, and material properties for normal, pathologic, and repair
      cartilage are summarized. In the third part, the relationship between mechanical
      loading of the cells and their corresponding biological responses are discussed.
      The goal for treating joint degeneration in the future lies in cartilage
      regeneration rather than prosthetic replacement. In order to achieve this goal,
      it has to be understood how structure and function, metabolic and biochemical
      properties, and biomechanical performance of articular cartilage can be restored.

PMID- 10952107
TI  - Cognitive psychology: implications for teaching and learning in radiology.

PMID- 10952108
TI  - Axial bone mineral density in patients with acromegaly.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to assess the influence
      of long-term elevated levels of growth hormone and insulin-like growth factor I
      on bone mineral density (BMD) of the spine in patients with acromegaly. MATERIALS
      AND METHODS: The spinal BMD in 40 patients with acromegaly was measured with
      quantitative computed tomography. The result was expressed as the mean of six
      measurements of consecutive vertebral bodies and as a z score. Twenty age- and
      sex-matched healthy persons also underwent spinal BMD measurement and served as
      controls. RESULTS: In 36 of the 40 patients, the BMD z score ranged within 2
      standard deviations (SDs) above or below the mean. Only two patients (one man and
      one woman) had enhanced BMD loss (below 2 SD). Two other female patients had BMD
      values of more than 2 SD above the mean. Differences between patient subgroups
      were not statistically significant, but a statistically significant (P < .05)
      positive correlation was found between basal serum concentration of growth
      hormone and spinal BMD for the entire patient group. No correlation between BMD
      and basal serum concentration of insulin-like growth factor I was found.
      CONCLUSION: Hypersecretion of growth hormone in patients with acromegaly,
      regardless of other factors, has no evident effect on BMD of the lumbar spine.

PMID- 10952109
TI  - Applying computer-assisted detection schemes to digitized mammograms after JPEG
      data compression: an assessment.
AB  - RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of Joint
      Photographic Experts Group (JPEG) image data compression on the performance of
      computer-assisted detection (CAD) schemes for the detection of masses and
      microcalcification clusters on digitized mammograms. MATERIALS AND METHODS: This
      study included 952 mammograms that were digitized and compressed with a JPEG
      compatible image-compression scheme. A CAD scheme, previously developed in the
      authors' laboratory and optimized for noncompressed images, was applied to
      reconstructed images after compression at five levels. The performance was
      compared with that obtained with the original noncompressed digitized images.
      RESULTS: For mass detection, there were no significant differences in performance
      between noncompressed and compressed images for true-positive regions (P = .25)
      or false-positive regions (P = .40). In all six modes the scheme identified 80%
      of masses with less than one false-positive region per image. For the detection
      of microcalcification clusters, there was significant performance degradation (P
      < .001) at all compression levels. Detection sensitivity was reduced by 4%-10% as
      compression ratios increased from 17:1 to 62:1. At the same time, the false
      positive detection rate was increased by 91%-140%. CONCLUSION: The JPEG algorithm
      did not adversely affect the performance of the CAD scheme for detecting masses,
      but it did significantly affect the detection of microcalcification clusters.

PMID- 10952110
TI  - Are NBME examination scores useful in selecting radiology residency candidates?
AB  - RATIONALE AND OBJECTIVES: The quality of the graduates of radiology residency
      programs is powerfully affected by the quality of the candidates admitted to
      them, making the evaluation and ranking of residency applicants one of the most
      important tasks of radiology education. In the applicant evaluation process,
      evaluators frequently take into account applicants' scores on the National Board
      of Medical Examiners (NBME) examination, operating on the implicit assumption
      that these scores help predict future performance as residents. The purpose of
      this study was to test that assumption. MATERIALS AND METHODS: Using a data set
      consisting of information about 99 residents admitted over a period of 10
      residency class years, the authors compared scores for parts I and II of the NBME
      examination with later results on the American Board of Radiology (ABR) written
      and oral examinations. Logistic regression was used to model differences in
      resident performance on the NBME and ABR examinations and to determine whether
      variance in ABR results could be predicted by variance in NBME examination
      scores. RESULTS: The authors were unable to demonstrate any statistically
      significant value of NBME examination scores in predicting eventual performance
      on the ABR written and oral examinations. CONCLUSION: The authors' attempt to
      validate the widespread practice of using NBME examination scores to evaluate and
      rank applicants to radiology residency programs demonstrated no discernible value
      for these scores in predicting the success of residents on the ABR examinations.

PMID- 10952111
TI  - Fast iterative algorithm for metal artifact reduction in X-ray CT.
AB  - RATIONALE AND OBJECTIVES: The reduction of metal artifacts in x-ray computed
      tomography (CT) has important clinical applications. An iterative method adapted
      from the expectation maximization (EM) formula for emission CT was shown to be
      effective for metal artifact reduction, but its computational speed is slow. The
      goal of this project was to accelerate that iterative method for metal artifact
      reduction. MATERIALS AND METHODS: Using the row-action/ordered-subset (EM)
      formula for emission CT as a basis, the authors developed a fast iterative
      algorithm for metal artifact reduction. In each iteration of this algorithm, both
      reprojection from an intermediate image and backprojection from discrepancy data
      are performed. RESULTS: The feasibility of the fast iterative algorithm was
      demonstrated in numerical and phantom experiments. In comparison with the
      nonaccelerated iterative algorithm, the speed of iterative metal artifact
      reduction is improved by an order of magnitude given image quality in terms of
      visual inspection, I-divergence in the projection domain, and the euclidean
      distance in the image domain. CONCLUSION: The fast iterative algorithm corrects
      intermediate reconstruction according to subsets of projections and produces
      satisfactory image quality at a much faster speed than the previously published
      iterative algorithm. This algorithm has important potential in clinical
      applications, such as orthopedic, oncologic, and dental imaging.

PMID- 10952112
TI  - Cervical spine standards for flexion radiograph interspinous distance ratios in
      children.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to quantitate the
      interspinous distances in a group of children as they underwent flexion during
      lateral radiography. MATERIALS AND METHODS: The cases of 59 children with minor
      trauma who underwent lateral flexion radiography were studied retrospectively.
      Measurements of each cervical interspinous distance and anteroposterior diameter
      of the adjacent body were used to calculate a ratio of interspinous distance to
      vertebral body diameter at each level. Linear regression analyses of each ratio
      to patient age were performed, and means and standard deviations of the ratios at
      each level were calculated. RESULTS: The ratios did not correlate in a
      statistically significant manner at any level with age. Therefore, data from all
      59 children were used to calculate the mean and standard deviation at each
      cervical level. Most children with severe ligamentous injury who were considered
      for fusion had interspinous ratios greater than 2 standard deviations above the
      mean for the control group. CONCLUSION: Standards for interspinous distances
      during flexion by children are presented. These standards may prove to be helpful
      in the evaluation of children for cervical ligamentous injury.

PMID- 10952113
TI  - Preview method for electron-beam CT scanning of the coronary arteries.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate a method that
      uses electron-beam computed tomography to obtain the most appropriate starting
      level for complete imaging of the coronary tree and to compare it with the
      existing method. A second aim was to evaluate the spatial location of the
      coronary arteries relative to different anatomic cardiac and chest landmarks.
      MATERIALS AND METHODS: Two hundred forty consecutive patients were randomly
      assigned to imaging with either a six-level preview (new) method or the
      traditional preview method. The accuracy of each preview method to encompass the
      coronary anatomy was compared. RESULTS: All coronary arteries were included in 3
      mm scans obtained starting three levels above the origin of the left main
      coronary artery. The left anterior descending coronary artery extended 3-9 mm
      above the left main artery in 33 patients (14%). The coronary arteries were
      encompassed by scans depicting 72-105 mm; thus, with 3-mm sections, up to 35
      scans are necessary to cover the entire coronary tree. No stable relationship
      between the coronary arteries and the pulmonary artery or carina could be found.
      CONCLUSION: The six-level preview method that identifies the left main coronary
      artery and begins 9 mm above this level is the most accurate method for depicting
      the coronary anatomy. No anatomic landmarks in the heart or chest can be used
      reliably to identify the position of the coronary arteries in individual
      patients.

PMID- 10952114
TI  - MR volumetric analysis of the human basal ganglia: normative data.
AB  - RATIONALE AND OBJECTIVES: The authors undertook this study to identify a precise,
      semiautomated, reproducible magnetic resonance (MR) imaging technique for
      measuring the basal ganglia, to establish normative volumetric data, and to
      verify the presence of previously reported asymmetries. MATERIALS AND METHODS:
      Twenty-eight healthy adults underwent cranial MR examination. The volumes of the
      various components of the basal ganglia were measured by means of a combination
      of thresholding and manual tracing techniques performed with specialized
      software. The validity of these measurements was assessed by fashioning, imaging,
      and measuring a practical basal ganglia phantom. Measurement accuracy was also
      established by means of inter- and intrarater reliability indexes. Normalized
      volumes were statistically analyzed with analysis of variance and paired t tests.
      RESULTS: The absolute values of the various components of the basal ganglia
      varied widely even though the volumes were normalized to differences in
      intracranial volume. The right caudate nucleus volume was significantly (P <
      .000001) larger than the left in both men and women and in both right-handed and
      non-right-handed subjects. This asymmetry led to an increase in the overall
      volume of the basal ganglia on the right. CONCLUSION: The authors have defined a
      precise, reproducible technique for measuring various components of the basal
      ganglia and have established normative data. The basal ganglia, similar to other
      brain structures, exhibit hemispheric lateralization.

PMID- 10952115
TI  - How well does applicant rank order predict subsequent performance during
      radiology residency?
AB  - RATIONALE AND OBJECTIVES: Residency selection committees expend substantial time
      and resources on assessing the quality of residency applicants to derive an
      appropriate rank order for the National Residency Matching Program. The authors
      determined whether there is a relationship between the rank number or rank
      percentile of applicants selected for a residency training program and subsequent
      radiology residency performance. MATERIALS AND METHODS: Records of radiology
      residents completing their residency between 1991 and 1998 were reviewed.
      Available rank numbers and rank percentiles for each resident were compared with
      subsequent performance, as assessed subjectively by 4th-year radiology rotation
      evaluation forms and retrospective recall of four senior faculty members and
      objectively by numerical and percentile scores on the written portion of the
      American Board of Radiology (ABR) examinations. Correlation coefficients were
      obtained for each comparison. RESULTS: Rank number and rank percentile were not
      significantly correlated with 4th-year resident rotation evaluations or ABR
      written examination scores or percentiles. A small correlation existed between
      rank order and retrospective evaluation of resident performance by the four
      senior faculty. CONCLUSION: Applicant rank number and rank percentile do not
      correlate with subsequent radiology residency performance as assessed on rotation
      evaluation forms or the ABR written examinations.

PMID- 10952116
TI  - Illuminating the "black boxes" of learning and recall.

PMID- 10952117
TI  - Stereotactic core breast biopsy.

PMID- 10952118
TI  - Congressional update: report from the Biomedical Imaging Program of the National
      Cancer Institute. Training the next generation of imaging scientists and
      clinicians.

PMID- 10952119
TI  - Paclitaxel (Taxol)/carboplatin combination chemotherapy in the treatment of
      advanced ovarian cancer.
AB  - The activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)
      in advanced ovarian cancer, both as a single agent and in combination
      chemotherapy, has been demonstrated in numerous phase I/II trials.
      Paclitaxel/platinum combinations have produced encouraging results in phase III
      trials and are now considered standard therapy for advanced disease. Carboplatin,
      an effective but more tolerable analog of cisplatin, has been substituted for
      cisplatin to reduce the toxicity of the paclitaxel/cisplatin regimen. A recent
      phase III equivalency trial of the Gynecologic Oncology Group (GOG 158) was
      conducted to rigorously compare paclitaxel/carboplatin with paclitaxel/cisplatin
      in the treatment of optimal stage III ovarian cancer. In a preliminary analysis
      of this trial, paclitaxel/carboplatin was better tolerated with no apparent
      difference in efficacy from paclitaxel/cisplatin. The improved toxicity profile
      and equivalent activity of paclitaxel/carboplatin also are suggested by
      preliminary results from other phase III trials. The results indicate that
      paclitaxel/carboplatin has a higher therapeutic index and is preferred over
      paclitaxel/cisplatin for advanced ovarian cancer.

PMID- 10952121
TI  - Chemotherapy for advanced ovarian cancer: overview of randomized trials.
AB  - Until the mid-1970s, standard therapy for ovarian carcinoma was a single
      alkylating agent. Subsequently, combination chemotherapy was shown to be superior
      to such therapy. During the 1980s, cisplatin-based combination chemotherapy
      became the standard chemotherapy regimen for advanced ovarian cancer; however,
      other classes of agents with documented activity against ovarian tumors appeared
      to be cross-resistant with platinum. The introduction of paclitaxel (Taxol;
      Bristol-Myers Squibb Company, Princeton, NJ) in the early 1990s, with its
      apparent lack of cross-resistance with platinum compounds, was a notable advance
      in ovarian cancer management that dramatically altered the standard of care.
      During the 1990s, the combination of platinum (cisplatin or carboplatin) plus
      paclitaxel rapidly evolved into front-line chemotherapy for advanced ovarian
      cancer. The series of randomized phase III studies that have compared the
      activity of platinum/paclitaxel with alternative regimens, including the previous
      standard combination of cisplatin/cyclophosphamide, support the combination of
      platinum/paclitaxel as the current standard chemotherapy for advanced ovarian
      cancer. Outstanding issues that stem from this phase III experience include the
      impact of nonprotocol salvage regimens on survival and the potential benefits of
      sequential single-agent regimens.

PMID- 10952120
TI  - Three cycles versus six cycles of adjuvant paclitaxel (Taxol)/carboplatin in
      early stage ovarian cancer.
AB  - The optimal management of early stage ovarian cancer with poor prognostic
      features remains controversial. On the basis of results of studies in advanced
      ovarian cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)
      in combination with a platinum agent has become part of adjuvant chemotherapy
      trials in early stage disease. Because the optimal number of chemotherapy cycles
      has not been determined, the Gynecologic Oncology Group is conducting a study
      comparing three cycles with six cycles of adjuvant paclitaxel/carboplatin in high
      risk patients with early stage ovarian cancer. At a median follow-up period of 3
      years, 290 (88%) of the 331 evaluable patients on both arms of the trial were
      alive and recurrence free. Regimen B (treatment groups have not yet been
      unblinded) was associated with a somewhat higher incidence of grade 3/4
      leukopenia and a markedly higher frequency of grade 2-4 neurologic toxicity.
      Final results from this study will reveal any difference in overall or
      progression-free survival between the two regimens.

PMID- 10952122
TI  - Surgery for recurrent ovarian cancer.
AB  - Recurrent ovarian cancer is associated with a poor long-term prognosis and
      optimal management for this problem is not well defined. The benefits of primary
      surgical cytoreduction in prolonging survival rates in advanced ovarian cancer
      have prompted examination of the potential role of secondary cytoreductive
      surgery in patients with recurrent disease or disease that progresses or
      stabilizes during primary adjuvant chemotherapy. No randomized clinical trials
      have been performed to evaluate secondary surgery in these settings. Based on
      available data, secondary surgery does not appear to improve survival in patients
      whose disease progresses or stabilizes during primary adjuvant chemotherapy and
      therefore is not recommended. The most promising experience with secondary
      surgery has been in patients with recurrent disease following optimal primary
      surgical resection with a recurrence-free interval of at least 1 year. While
      secondary surgery is feasible, it has not yet been proven to improve survival, as
      similar survival rates have been reported using chemotherapy alone. Consequently,
      it is critical to minimize the risk of morbidity through careful patient
      selection when secondary surgery is used.

PMID- 10952123
TI  - Innovative therapies for advanced ovarian cancer.
AB  - The emergence of drug-resistant tumors during therapy for ovarian cancer remains
      an obstacle to improving long-term outcomes. Active areas of ovarian cancer
      research include clinical evaluation of non-cross-resistant antineoplastic agents
      that demonstrated single-agent activity in ovarian cancer during the 1990s:
      oxaliplatin, the new anthracyclines (epirubicin, liposomal doxorubicin),
      topotecan, oral etoposide, gemcitabine, and vinorelbine. Most of these new agents
      are currently being evaluated as a component of doublet and triplet combination
      regimens for advanced ovarian cancer, with use of sequential alternating doublet
      regimens gaining interest. The potential role of intraperitoneal therapy
      continues to be investigated. In addition, there are a variety of innovative
      treatment strategies on the horizon that are targeted at underlying disease
      processes, including anticancer vaccines, gene therapy, and antiangiogenic
      therapy. Based on this multitude of investigational questions and the low cure
      rates currently achieved, all women with advanced ovarian cancer should be
      offered participation in clinical trials.

PMID- 10952124
TI  - Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian
      cancer.
AB  - Primary surgical cytoreduction followed by chemotherapy usually is the preferred
      management of advanced (stage III or IV) ovarian cancer. The presence of residual
      disease after surgery is one of the most important adverse prognostic factors for
      survival. Neoadjuvant chemotherapy has been proposed as an alternative approach
      to conventional surgery as initial management of bulky ovarian cancer, with the
      goal of improving surgical quality. Since 1989, we have been treating advanced
      epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary
      cytoreductive surgery in approximately half of the patients with stage III-IV
      disease. Selection of neoadjuvant chemotherapy was based on disease-related
      characteristics (eg, metastatic tumor load, stage of disease, performance
      status). Since 1993, open laparoscopy also has been used to aid in evaluating
      operability. A retrospective analysis of 338 patients was conducted to compare
      outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those
      observed during 1980 to 1988, when all patients underwent primary cytoreductive
      surgery. Crude 3-year survival rates were higher and postoperative mortality
      rates were lower during the second time period compared with the first. Overall,
      the results suggest that neoadjuvant chemotherapy results in survival rates in
      selected patients with advanced ovarian cancer that are comparable with those
      associated with primary cytoreductive surgery. Patients with stage IV disease,
      total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped
      peritoneal metastases, and/or a poor performance status are probably the best
      candidates for this alternative approach. A prospective randomized study of
      neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.

PMID- 10952125
TI  - Weekly paclitaxel in the management of ovarian cancer.
AB  - The weekly administration of paclitaxel has the potential to increase the
      effectiveness of this cycle-specific agent against slowly growing solid tumors.
      Clinical evaluation has confirmed that paclitaxel can be safely delivered on a
      weekly schedule as a 1-hour infusion, with objective responses being observed in
      platinum-resistant ovarian cancer. Limited data suggest that the schedule may
      also possess activity against tumors previously demonstrated to be resistant to
      paclitaxel-containing regimens delivered on an every-3-week schedule. Ongoing
      trials in ovarian cancer are examining the clinical utility of this approach as a
      second-line treatment option in carefully defined paclitaxel-resistant disease
      and as a consolidation strategy in high-risk, early stage disease following
      initial therapy with a carboplatin/paclitaxel combination regimen.

PMID- 10952126
TI  - High-dose chemotherapeutic approaches to ovarian cancer management.
AB  - The effect of high-dose chemotherapy on the survival of women with ovarian cancer
      has been studied in numerous clinical trials. Approaches to dose intensity have
      included high-dose chemotherapy, combination platinum therapies, intraperitoneal
      therapy, and stem cell-supported high-dose chemotherapy. Taken together, the data
      demonstrate increased response rates with high-dose regimens, but any survival
      advantages observed have been limited. Patients with the most favorable outcome
      are those with low tumor burden and chemotherapy-sensitive tumors. An attempt to
      study this group of patients in a randomized trial in the United States
      (Gynecologic Oncology Group Protocol 164) was unsuccessful because of low
      accrual. Reasons for low accrual included physician bias, patient bias, and lack
      of third-party payer support. European randomized trials are under way to
      evaluate high-dose chemotherapy and stem cell transplantation as part of initial
      therapy or as consolidation after initial response to therapy and to compare high
      dose chemotherapy with standard-dose chemotherapy. Until results from these
      trials become available, high-dose therapy remains limited to the clinical trial
      setting.

PMID- 10952127
TI  - Management of advanced ovarian cancer consensus summary. Advanced Ovarian Cancer
      Consensus Faculty.

PMID- 10952128
TI  - 2D NMR analysis of highly restricted internal rotation in 2-methylthio-3H-4-p
      bromophenyl)-7-[(ortho- and para-substituted)-phenylthio]-1, 5-benzodiazepines.
AB  - The complete assignments of twelve 4-aryl-7-thioaryl-1,5-benzodiazepines 1H and
      13C spectra, performed with the use of high resolution variable solvent and
      temperature 1D and 2D techniques (e.g. HOMOCOSY, NOESY, HMQC and HMBC), lead to
      the determination of conformational equilibria between two rotamers having the
      aromatic ring of the thioaryl oriented in a perpendicular or helical orientation
      toward the benzodiazepine ring. The restricted rotation was evaluated from the
      population of these conformers.

PMID- 10952129
TI  - NMR observation of hydrolysis of acetonitrile to acetamide catalyzed by binuclear
      silver cryptate.
AB  - NMR analyses (TOCSY, HMQC and DOSY) indicate that, in the presence of water,
      acetonitrile is exclusively hydrolyzed to acetamide catalyzed by bisilver
      cryptate complex, which contains coordinating acetonitrile molecule.

PMID- 10952130
TI  - Raman spectroscopy of urea and urea-intercalated kaolinites at 77 K.
AB  - The Raman spectra of urea and urea-intercalated kaolinites have been recorded at
      77 K using a Renishaw Raman microprobe equipped with liquid nitrogen cooled
      microscope stage. The NH2 stretching modes of urea were observed as four bands at
      3250, 3321, 3355 and 3425 cm(-1) at 77 K. These four bands are attributed to a
      change in conformation upon cooling to liquid nitrogen temperature. Upon
      intercalation of urea into both low and high defect kaolinites, only two bands
      were observed near 3390 and 3410 cm(-1). This is explained by hydrogen bonding
      between the amine groups of urea and oxygen atoms of the siloxane layer of
      kaolinite with only one urea conformation. When the intercalated low defect
      kaolinite was cooled to 77 K, the bands near 3700 cm(-1) attributed to the
      stretching modes of the inner surface hydroxyls disappeared and a new band was
      observed at 3615 cm(-1). This is explained by the breaking of hydrogen bonds
      involving OH groups of the gibbsite-like layer and formation of new bonds to the
      C=O group of the intercalated urea. Thus it is suggested that at low temperatures
      two kinds of hydrogen bonds are formed by urea molecules in urea-intercalated
      kaolinite.

PMID- 10952131
TI  - Raman study on conformational equilibria of fluoroacetone in aqueous solutions.
AB  - The effects of water and heavy water on conformational equilibria of
      fluoroacetone have been investigated via Raman spectroscopy. Additional Raman
      bands have been observed in the C-F stretching and the C-C-C symmetric stretching
      regions for the aqueous solutions. Based on enthalpy and volume differences
      between the conformers, these bands are assigned to the syn conformer which has
      hydrogen bonds between the fluorine atom and water molecules (syn' conformer).
      The number of H2O molecules binding to the syn' conformer is estimated to be 2.4
      from the concentration dependence of the spectrum. The enthalpy and the volume
      differences between the cis and syn conformers in the aqueous solutions show
      anomalous values in comparison with those in organic solvents. We discuss these
      thermodynamic behaviors from the viewpoint of the hydration structures of
      fluoroacetone.

PMID- 10952132
TI  - The role of molecular size in the excited state behavior of aminocoumarin dyes in
      restricted media--2: study of BC I in AOT-formamide reversed micelles.
AB  - Ground and excited state properties of a pre-twisted 7-diethylaminocoumarin dye
      (BC I) belonging to the family of coumarinyl benzopyrano pyridines are reported
      in isooctane-AOT-formamide reversed micelles. In reversed micelles, BC I, albeit
      soluble in formamide, is found to remain out of the polar solvent pool. But the
      photophysical properties of the probe dye are sensitive to the changes in the
      polarity of the interfacial region caused by increase in F0 = [formamide]/[AOT].
      The spectroscopic properties and dynamics are indicative of dual emission due to
      the solubilization of the dye in two different environments (the nonpolar solvent
      and the interfacial region). Results of the steady-state fluorescence anisotropy
      experiments also support the presence of two different environments. The present
      study once again proves that molecular size is an important parameter in the
      study of the photophysical properties of the flexible aminocoumarin dyes in
      reversed micelles.

PMID- 10952133
TI  - Effect of water on the formamide-intercalation of kaolinite.
AB  - The molecular structures of low defect kaolinite completely intercalated with
      formamide and formamide-water mixtures have been determined using a combination
      of X-ray diffraction, thermoanalytical techniques, DRIFT and Raman spectroscopy.
      Expansion of the kaolinite to 10.09 A was observed with subtle differences
      whether the kaolinite was expanded with formamide or formamide-water mixtures.
      Thermal analysis showed that greater amounts of formamide could be intercalated
      into the kaolinite in the presence of water. New infrared bands were observed for
      the formamide intercalated kaolinites at 3648, 3630 and 3606 cm(-1). These bands
      are attributed to the hydroxyl stretching frequencies of the inner surface
      hydroxyls hydrogen bonded to formamide with water, formamide and interlamellar
      water. Bands were observed at similar positions in the Raman spectrum. At liquid
      nitrogen temperature, the 3630 cm(-1) Raman band separated into two bands at 3633
      and 3625 cm(-1). DRIFT spectra showed the hydroxyl deformation mode at 905 cm(
      1). Changes in the molecular structure of the formamide are observed through both
      the NH stretching vibrations and the amide 1 and 2 bands. Upon intercalation of
      kaolinite with formamide, bands are observed at 3460, 3344, 3248 and 3167 cm(-1)
      attributed to the NH stretching vibration of the NH involved with hydrogen bonded
      to the oxygens of the kaolinite siloxane surface. In the DRIFT spectra of the
      formamide intercalated kaolinites bands are observed at 1700 and 1671 cm(-1) and
      are attributed to the amide 1 and amide 2 vibrations.

PMID- 10952134
TI  - Infrared and XAFS study on structure and transition behavior of zinc stearate.
AB  - Structure and transition behavior of zinc(II) stearate crystal were investigated
      by infrared and XAFS spectroscopies. Structure of zinc stearate at room
      temperature was estimated as follows. From XAFS analysis, the coordination number
      of the carboxylate groups around the zinc atom was evaluated as 4 and the Zn-O
      distance as 1.95 A. Based on the infrared spectrum and a normal mode analysis,
      the conformation of the alkyl chain was confirmed as all-trans and the sub-cell
      packing was considered as parallel type, and also the coordination form of the
      carboxylate groups was determined as bridging bidentate type. As increasing
      temperature, zinc stearate has a solid liquid phase transition at 130 degrees C.
      At the transition, the alkyl chains goes into liquid like state as reported by
      Mesubi but the coordination structure was confirmed to be maintained.

PMID- 10952135
TI  - [Study of the electronic transitions of azulene and several of it's derivitives
      and their auto-association by the monopole-dipole atomic interaction (AMDI)
      model].
AB  - The corresponding hydrogen, carbon and nitrogen atomic dipolar polarisabilities
      and effective charges given by Fraga are used for the determination of
      theoretical UV absorption spectra of azulene, 1,3-diaza-azulene and 2-phenyl-1,3
      diaza-azulene and their self-associations. These spectra are obtained for the
      first time using the atom monopole dipole interaction model and compared to those
      given experimentally by other authors.

PMID- 10952136
TI  - Effect of zeolite properties on ground-state and triplet-triplet absorption,
      prompt and oxygen induced delayed fluorescence of tetraphenylporphyrin at
      gas/solid interface.
AB  - The ground-state and transient absorption, prompt and delayed fluorescence of
      tetraphenylporphyrin (TPP) adsorbed onto the external surface of different
      zeolites was monitored using diffuse-reflectance steady-state and laser flash
      photolysis. The delayed fluorescence (DF) of TPP detected in the presence of O2
      is attributed to the energy transfer from 3TPP to 3O2 to form 1O2 and subsequent
      energy transfer from 1O2 to some other 3TPP within the organised molecular
      ensembles on the zeolite surface. The spectroscopic and kinetic parameters,
      namely the yield of DF (2-20% relative to prompt fluorescence), depend on the
      zeolite properties: the observed differences were correlated with the acid-base
      properties of the two zeolite series studied in this work (KA, NaA, CaA) and
      (NaA, NaX, NaY).

PMID- 10952137
TI  - Absorption and emission characteristics of Er3+ ions in alkali
      chloroborophosphate glasses.
AB  - Alkali chloroborophosphate glasses containing 1 mol% of Er3+ ions were studied
      experimentally using the absorption and emission spectroscopy. The energy level
      scheme for the 4f11 (Er3+) electronic configuration was deduced from the observed
      band energies of the absorption spectra in terms of a parametrized Hamiltonian
      using the various free-ion spectroscopic parameters. Oscillator strengths (f)
      measured from the absorption spectra have been analyzed using the Judd-Ofelt
      theory to evaluate the three intensity parameters omegalambda (lambda = 2, 4 and
      6). Reasonable agreement between the measured and calculated f values has been
      found. Electric and magnetic dipole transition probabilities, fluorescence
      branching ratios, integrated emission cross sections and radiative lifetimes were
      calculated for all the excited states of Er3+ ions. The non-radiative (WNR)
      relaxation rates from the excited levels to the next lower levels have been
      calculated and the relationship between the energy gap and non-radiative
      relaxation rate has been established. These results were used to predict the
      possible potential laser transitions in Er-doped alkali chloroborophosphate
      glasses.

PMID- 10952138
TI  - Spectral properties of (5-phenyl-1,3,4-oxadiazol-2-yl)-7-hydroxycoumarin (POHC).
AB  - The electronic absorption, emission and excitation spectra of POHC were measured
      in different solvents and are affected by solvent polarity. The fluorescence
      quantum yield of POHC decreases with increasing Richardt and Dimorth solvent
      parameter (E(T)) value of the solvent. In dilute solutions POHC is almost totally
      present in its protonated nitrogen tautomer form. The deprotonation is a
      reversible process. A shoulder in the absorption spectra at approximately 473 nm
      indicates the presence of a portion of the tautomer (s) that disappears on
      lowering the temperature. Molecular oxygen acts as a quencher with quenching rate
      constant of 1.8 x 10(10) M(-1) s(-1) in DMF. Energy transfer from POHC to
      rhodamine 6G in ethanol was also studied. POHC is relatively photostable in
      ethanol (phic approximately 1.7 x 10(-4)). Quantum chemical calculations were
      carried out and correlated to experimental observations.

PMID- 10952139
TI  - Temperature effect on the 13C NMR chemical shift of pressurized CO2 containing
      selected modifiers.
AB  - Temperature dependence of 13C NMR chemical shift of pressurized CO2 containing
      modifiers has been studied. Benzene, C6F6, C6F5OH, (CF3)2CHOH and [(CH3)2N]3PO
      were used as the modifiers. The 13C chemical shift of CO2 was found to show a
      different temperature dependence in the presence of selected modifiers.

PMID- 10952140
TI  - Study on three-dimensional fluorescent spectral characteristics of
      fluoroquinolones in varying media.
AB  - Behaviors of fluoroquinolones in varying media were observed by employing their
      intrinsic fluorescence. Spectral characteristics in reversed micelles (Aerosol
      OT/n-octane) were compared with those in aqueous solution and micelles (sodium
      dodecyl sulfonate). Those differences in interactions between fluoroquinolones
      and the various media were clearly illustrated by three-dimensional fluorescent
      spectra. The influences of other environmental factors on spectral
      characteristics (pH, SDS concentration, etc.) were also investigated.

PMID- 10952141
TI  - Energy transfer characteristics of the hydrogen peroxide induced Ce3+-Ce4+
      mixture.
AB  - Luminescence of Ce3+ in the hydrogen peroxide induced sulfuric acid solutions was
      observed to be quenched by Ce4+ ions in the solution by energy transfer due to
      electric dipole interaction between Ce3+ and Ce4+. A systematic investigation of
      the energy transfer characteristics of Ce3+-Ce4+ mixture has been made by
      measuring the absorption, luminescence and excitation spectra at room
      temperature. The effect of the concentration of Ce3+ on the energy transfer
      process has been also studied and the critical transfer distance (Ro) has been
      calculated considering Forster type interaction between the ions and found to be
      8.7 A for the mixture of 1 x 10(-4) mol 1(-1) Ce3+ and 3 x 10(-4) mol l(-1) Ce4+.

PMID- 10952142
TI  - Vibrational spectra of the adduct of 1,8-bis(dimethylamino)naphthalene with
      dichloromaleic acid (DMAN x DCM).
AB  - The infra-red (IR), Raman (R) and inelastic incoherent neutron scattering (IINS)
      spectra, particularly in low frequency region, of the title ionic adduct were
      studied. It is shown that all low frequency vibrations (below 200 cm(-1)) of
      (CH3)2N groups of protonated 1,8-bis(dimethylamino)naphthalene (DMAN)--clearly
      observed in IINS spectra--are sensitive to the environment, i.e. to the type of
      counterion forming short contacts with C-H bonds of methyl groups. The internal
      frequencies were also calculated by ab initio method. The results are consistent
      with numerous observations of the counteranion effect on the geometry of the
      protonated DMAN. The conclusions are compared with structural and NMR studies
      reported recently for the 1,8-bis(dimethylamino)naphthalene with dichloromaleic
      acid (DMAN x DCM) adduct. The single crystal R polarized spectra taken over the
      frequency range 20-3200 cm(-1) were analyzed in detail. We have shown that a
      substantial difference in the IR spectrum of the dichloromaleic acid (DCM) anion
      in the DMAN adduct and in the potassium salt results from different geometries of
      OHO hydrogen bonds. In the case of potassium salt the chains of longer
      intermolecular hydrogen bonds are formed described by means of a double minimum
      potential.

PMID- 10952143
TI  - IR spectra of CH3F in liquid and solid noble gas solutions.
AB  - The IR absorption spectra of CH3F doped Ar, Kr and Xe solutions have been
      recorded near the melting point. The full widths at half maximum of fundamental
      bands increase noticeably after crystallization of the Xe and Kr solutions. A
      slight narrowing of the bands is observed just below the freezing point of the Ar
      solution. Treated in the framework of the Debye model for the J-diffusion of a
      symmetric top rotation, the results suggest a weaker perturbation of rotational
      motion of CH3F in the ordered Xe and Kr solids at least near the freezing point.
      At the same time, molecular rotation becomes more hindered when going to solid
      Ar. The broadening effect has been found to correlate with a hopping increase of
      the vibrational energy relaxation time, measured by the IR-IR double resonance
      method.

PMID- 10952144
TI  - Identification of silicooxygen rings in SiO2 based on IR spectra.
AB  - In this work application of IR spectra for the determination of silcooxygen ring
      types in framework silicates structures has been presented. Results of the
      spectra interpretation for cyclosilicates ('isolated' silicooxygen rings) have
      been adopted for the spectra of highly polymerized SiO2 structures. In such
      structures, silicooxygen rings are interconnected. In this work, spectra of three
      basic polymorphous SiO2 types, i.e. cristobalite, tridymite quartz (in various
      temperature forms) and v-SiO2 are discussed. It has been shown that
      identification of rings is possible after precise analysis of the spectra
      preceded by mathematical decomposition.

PMID- 10952145
TI  - Molecular spectroscopy study of the reaction of nucleic acids with brilliant
      cresol blue.
AB  - The interaction of brilliant cresol blue (BCB) with nucleic acids in aqueous
      solution has been studied by spectrophotometry and Rayleigh light scattering
      (RLS) spectroscopy. Under suitable conditions, the RLS spectra of BCB changed
      significantly due to the presence of nucleic acids. RLS intensity of BCB at 364
      nm is greatly enhanced with the addition of nucleic acids, and a new RLS peak is
      observed at 552 nm. This peak is about half the intensity of that at 364 nm. The
      results of this study show that BCB interacts with DNA possibly due to the
      cooperative effect of electrostatic attraction, intercalation, coordination and
      hydrophobic effect. Under optimum conditions, the increase of RLS at 364 nm of a
      BCB solution is proportional to the concentration of nucleic acids added. This
      result is the basis for a new RLS method for determination of nucleic acids. The
      linear range of ctDNA, fsDNA and yRNA is 0.12-4.70, 0.11-4.64 and 0.43-7.07
      microg ml(-1), respectively.

PMID- 10952146
TI  - X-ray diffraction study of human serum.
AB  - Blood serum from people suffering from cancer and healthy subjects was subjected
      to a comparative study by X-ray diffraction. The diffraction patterns were
      referred to that of pure water. The patterns obtained for blood serum of healthy
      subjects were similar to that of pure water, while those of cancer patients (two
      kinds of cancer changes) were different. The former similarity is accounted for
      by the dominant interaction of water molecules in healthy blood serum with non
      polar side chains of amino acids, stabilising the serum structure. In samples
      from cancer patients the structure of water in blood serum is destroyed because
      of enhanced interactions of water with polar molecules of conformationally
      changed proteins. This observation suggests X-ray examination of blood serum from
      cancer patients and healthy subjects, indicating X-ray diffraction as a
      diagnostic tool for the occurrence of cancer. The results of this work have shown
      that the presence of protein affected by cancer has a destructive effect on the
      structure of water in human serum. The results reported confirm the earlier
      finding relating cancer changes to optical circular birefringence effects.

PMID- 10952147
TI  - Fluorescent studies on the binding-Ca2 + in fibrinolytic principle separated from
      snake venom.
AB  - By using equilibrium dialysis, atomic absorption spectrometry, fluorescence
      titration and determination of fluorescence lifetime, it can be determined that
      each fibrinolytic principle (FP) molecule contains one Ca2+-binding site and one
      Ca2+ ion, which can be substituted by a Tb3+ ion completely. The intramolecular
      energy transfer between Tb3+ and the tryptophan (Trp) residue in FP has been
      investigated through fluorescence spectroscopy. In the FP molecule, the excited
      energy can transfer from the Trp residue as an energy donor to the Tb3+ ion
      substituted as an acceptor. The distance between Tb3+ and the Trp residue,
      approximately 0.38 nm, has been calculated with the experimental data and Forster
      theory.

PMID- 10952149
TI  - Lack of a relation between serum potassium concentration and exercise hyperpnea
      in patients with chronic heart disease.
AB  - Exertional dyspnea, a major symptom of patients with chronic heart failure,
      mainly stems from an abnormally high ventilatory response to exercise. However,
      there has been considerable controversy surrounding the mechanisms of respiratory
      control during exercise, especially regarding the role of serum potassium. We
      investigated the relation between serum potassium concentration [K+] and
      ventilation (VE) during exercise before and after oral supplements of potassium
      chloride in cardiac patients. Thirteen patients with chronic heart disease
      performed a 6-min constant-work-rate exercise (65.8+/-11.1 W) with respiratory
      gas measurements before initiating oral supplements of potassium chloride, 4
      weeks after continued supplements, and 4 weeks after discontinuing supplements.
      Blood was sampled from a forearm vein at rest before exercise and at the end of
      exercise for measurement of [K+] and blood gases. The [K+] at rest was 3.66+/
      0.30 mmol/L before oral supplements of potassium and significantly increased to
      4.08+/-0.31 mmol/L (p<0.01) after supplements. In spite of the significant
      increases in the [K+], resting VE was not changed. While serum [K+] during
      exercise was significantly higher after potassium supplements than before,
      exercise VE was not influenced by the changes in [K+] throughout the study
      period. The findings of the present study strongly suggest that the chronic
      increase in the serum [K+] has no influence on the resting or exercise VE in
      patients with heart disease.

PMID- 10952148
TI  - Plasma and platelet plasminogen activator inhibitor-1 in patients with acute
      myocardial infarction.
AB  - Several studies have demonstrated an increased level of plasma plasminogen
      activator inhibitor-1 (PAI-1) in patients with coronary artery disease (CAD).
      However, the concentration of PAI-1 in platelets, which accounts for more than
      90% of the blood PAI-1, is unknown in these patients. The present study evaluated
      the concentrations of PAI-1 and several fibrinolytic factors in the plasma and
      platelets of patients with CAD and the serial changes in patients with acute
      myocardial infarction (AMI). All 72 subjects had coronary angiography and were
      divided into 3 groups: CAD(-) group without coronary artery stenosis or
      myocardial ischemia (n=20), CAD(+) group with either stable angina pectoris
      (n=18) or old myocardial infarction (n=12) with coronary artery stenosis, and the
      AMI group admitted within 24h of symptom onset who underwent successful
      percutaneous transluminal coronary angioplasty (n=22). The concentrations of
      plasma PAI-1, tissue plasminogen activator (t-PA), and t-PA x PAI-1 complex were
      similar in the CAD(-) and CAD(+) groups, but were greater on day 1 in the AMI
      group compared with the 2 CAD groups. There were no significant differences
      between the 3 groups in the plasma concentrations of thrombin antithrombin III
      complex (TAT), alpha2-plasmin inhibitor-plasmin complex (PIC), beta
      thromboglobulin (beta-TG), and platelet factor 4 (PF-4). The platelet PAI-1
      concentrations did not differ between the CAD(-) and CAD(+) groups, but was
      greater on day 1 in the AMI group compared to the CAD groups. The platelet beta
      TG and PF-4 were similar between the 3 groups. In the AMI group, both the plasma
      and platelet PAI-1 concentrations were greater on day 1, but the plasma PAI-1
      rapidly decreased by day 5 and remained low on day 28 compared with day 1. The
      platelet PAI-1 concentration gradually decreased by day 5 and was further
      decreased by day 28. The serial changes of the plasma t-PA and t-PA PAI-1 complex
      during the course of AMI were similar to those of the plasma PAI-1. A positive
      correlation was found between the plasma and platelet PAI-1 in all 72 patients,
      but not in the AMI group alone. These results suggest that the PAI-1 that has
      accumulated in platelets at the onset of AMI might be released in large amounts
      into the plasma, resulting in an increase in thrombus formation.

PMID- 10952150
TI  - New combined spasm provocation test in patients with rest angina: intracoronary
      injection of acetylcholine after intracoronary administration of ergonovine.
AB  - The incidence of provoked coronary spasm with the standard single spasm
      provocation test has been relatively low in patients with rest angina. The
      present study examined the clinical usefulness of a newly designed spasm
      provocation test, an intracoronary injection of acetylcholine (ACh) following an
      ergonovine (ER) test, in patients with rest angina who demonstrated low disease
      activity and atypical chest pain. Triple sequential spasm provocation tests were
      performed in 24 patients with atypical chest pain who had no ischemia and in 40
      patients with rest angina who had distinct ischemia. Initially, an ACh test (20
      100 microg) and then an ER test (40-64 microg) were performed and then, if no
      spasm was provoked, an intracoronary injection of ACh was given after the ER test
      to evaluate coronary spasm. Coronary spasm was defined as total or subtotal
      occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by
      intracoronary injection of either ACh or ER, but coronary spasms were induced in
      2 patients using the new method, with the remaining 22 not experiencing spasm
      (specificity of new method, 92%). In the 40 patients with rest angina,
      intracoronary injection of ACh induced coronary spasm in 22 patients (group I)
      and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary
      spasm was not induced by either the ACh test or the ER test in 12 patients (group
      III). The intracoronary administration of ACh after the ER test provoked spasm in
      11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients
      with rest angina, the frequency of chest pain attacks in 1 month experienced by
      patients in group III (0.8+/-0.8) was significantly lower than that of patients
      in group I (7.0+/-5.3, p<0.01) or II (3.5+/-2.3, p<0.05). No serious or
      irreversible complications related to this new combined method were observed. In
      conclusion, this method was safe and reliable for the induction of coronary spasm
      in patients with rest angina who may have low disease activity.

PMID- 10952151
TI  - Abnormal myocardial blood flow distribution in patients with angina pectoris and
      normal coronary arteriograms.
AB  - To evaluate coronary microvascular function and its relation to the genesis of
      chest pain and ST-segment depression during exercise in patients with syndrome X,
      pacing-induced changes in transmural myocardial blood flow distribution were
      quantitatively assessed by 2-dimensional myocardial contrast echocardiography. Of
      25 patients with a history of chest pain and normal coronary arteries with the
      negative ergonovine test, 11 had exercise-induced chest pain and ST-segment
      depression (syndrome X), and 14 did not (controls). Myocardial blood flow
      distribution before and after pacing stress was assessed by measuring the ratio
      of the endocardial to epicardial gray level (ie, endo/epi gray level ratio) in
      the territory of the left anterior descending coronary artery. Pacing-induced
      chest pain and ST-segment depression were observed in syndrome X, but not in
      controls. The endo/epi gray level ratio in syndrome X significantly decreased
      after pacing (from 0.98+/-0.10 to 0.76+/-0.17, p<0.01), but not in controls (from
      0.97+/-0.08 to 0.99+/-0.08, NS). Abnormal myocardial blood flow distribution may
      play an important role in exercise-induced chest pain and ST-segment depression
      in these patients.

PMID- 10952152
TI  - Effects of metabolically ischemic, but viable, myocardium on QT dispersion in
      patients with acute myocardial infarction: a study with resting I-123
      BMIPP/thallium-201 myocardial single-photon emission computed tomography.
AB  - In chronic Q-wave myocardial infarction, QT dispersion is closely correlated with
      infarct size, but this correlation has not been evaluated for acute myocardial
      infarction (AMI). The effects of abnormal fatty acid metabolism on QT dispersion
      were examined in 123 patients with AMI who underwent resting iodine-123-15
      iodophenyl 3-methyl pentadecanoic acid (BMIPP)/thallium-201(201Tl) myocardial
      single photon emission computed tomography (SPECT) and electrocardiographic
      analysis in the subacute phase. The relationship between BMIPP and 201Tl was
      defined as match when the total defect score for BMIPP was equal to or smaller
      than that for 201Tl, and as mismatch when the total defect score for BMIPP was
      larger than that for 201Tl. Twenty-six patients (21%) demonstrated BMIPP-201Tl
      match and 97 (79%) demonstrated mismatch. Infarct size was closely correlated
      with QT dispersion (r=0.67, p<0.001) in patients with BMIPP-201Tl match, but
      weakly correlated (r=0.30, p<0.005) in patients with BMIPP-201Tl mismatch. For
      small infarctions, QT dispersion was significantly larger in patients with BMIPP
      201Tl mismatch than in those with BMIPP-201Tl match (62+/-24 ms vs 41+/-18 ms,
      p=0.03), but did not differ between the 2 groups for large infarctions. This
      study shows that QT dispersion is influenced by infarct size and by the presence
      of metabolically ischemic but viable myocardium in patients with AMI.

PMID- 10952153
TI  - Efficacy of atrioventricular sequential pacing and diastolic mitral regurgitation
      in patients with intrinsic atrioventricular conduction.
AB  - The efficacy of a short atrioventricular (AV) delay in patients with dilated
      cardiomyopathy has been reported, but there are deleterious effects of right
      ventricular pacing. Diastolic mitral regurgitation (MR) is observed in patients
      with elevated left ventricular end-diastolic pressure and can be induced by
      prolonging the AV delay in patients with DDD pacemakers. The critical PQ interval
      that induces diastolic MR may represent the upper limit of the optimal PQ
      interval. The efficacy of AV sequential pacing and diastolic MR were studied in
      11 patients (68.3+/-13.7 (SD) years old) with intrinsic AV conduction and with
      implanted DDD pacemakers. Cardiac output (CO) and pulmonary capillary wedge
      pressure (PCWP) were measured by Swan-Ganz catheter and transmitral flow was
      recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by
      25 ms starting from 65 ms. Pacing rate was fixed at 70-80 beats/min. In 6 of the
      11 patients, diastolic MR was observed under atrial pacing and the critical PQ
      interval for the appearance of diastolic MR was 0.22+/-0.04 s. CO was increased
      from 3.8+/-0.8 to 4.3+/-0.9 L/min (p<0.05) and PCWP was decreased from 7.5+/-2.8
      to 5.5+/-1.6 mmHg (p<0.05) by shortening the AV delay till the diastolic MR
      disappeared. On the other hand, in 5 of the 11 patients, diastolic MR was not
      observed, and CO (4.2+/-0.5 to 4.3+/-0.5L/min, ns) and PCWP (5.8+/-4.6 to 5.4+/
      3.9 mmHg, ns) were not improved by AV sequential pacing. In conclusion, cardiac
      function may be improved by AV sequential pacing and setting the AV delay under
      the critical PQ interval for the appearance of diastolic MR when the diastolic MR
      is observed. However, AV sequential pacing may be either ineffective or even
      deleterious for patients in whom diastolic MR is not observed.

PMID- 10952154
TI  - Clinical assessment of a new method for pacing pulse detection using a hybrid
      circuit in digital Holter monitoring.
AB  - Holter monitoring is widely used for the detection of arrhythmia and ischemic
      episodes. Traditionally, analog amplitude-modulated Holter devices have been used
      for detecting arrhythmia, but they produce signal distortion due to contour
      effects and phase distortion caused by the tape recorders. A digital Holter
      device without these disadvantages has been developed and can reproduce
      clinically accurate electrocardiographic waveforms useful for assessment of
      arrhythmia and ST segments. However, their reliability is questionable when
      detecting pacing pulses in pacemaker patients. Because electrocardiographic
      signals are digitized based on sampling rate, pacing pulses are occasionally
      missed. Therefore, the FM-300 was developed, a new device for detecting pacing
      pulses on digital recordings that has both digital and analog circuits in one
      system and indicates pacing pulse timing with arrows. This device can
      automatically detect and recognize pacing pulses from various artifacts and
      pacing modalities, making it easy to identify pacing pulses on digitally recorded
      electrocardiograms. The FM-300 is useful in the diagnosis and assessment of
      pacemaker function and has improved the reliability of pulse detection in digital
      Holter monitoring.

PMID- 10952155
TI  - Peak systolic blood pressure in exercise testing is associated with scintigraphic
      severity of myocardial ischemia in patients with exercise-induced ST-segment
      depression.
AB  - Some electrocardiographic variables, including the degree of maximal ST-segment
      depression (STD), may not necessarily indicate the severity of exercise-induced
      myocardial ischemia. The present study examined whether maximal STD correlates
      with the severity and extent of exercise-induced myocardial ischemia, as assessed
      by thallium-201 (201Tl) imaging, and which parameter of exercise testing reflects
      scintigraphic severity and extent in 270 patients who had a 1 mm or greater
      horizontal or down-sloping STD on exercise 201Tl imaging. The scintigraphic
      severity and extent of exercise-induced ischemia was assessed and correlated with
      maximal STD, number of positive leads, workload, peak heart rate, peak systolic
      blood pressure (SBP), rate-pressure product, chest pain and the Duke treadmill
      score. Most of the scintigraphic markers of the severity and extent of ischemia
      had significant but weak correlation with all of those parameters. Multivariate
      analysis demonstrated that peak SBP and the Duke treadmill score (chest pain in
      only simple variables model) correlated independently with scintigraphic severity
      and extent of ischemia. Furthermore, most of the patients with a peak SBP of 200
      mmHg or more had milder and less extensive ischemia. In patients with exercise
      induced STD, the scintigraphic severity and extent of ischemia may be estimated
      by peak SBP and the Duke treadmill score.

PMID- 10952156
TI  - G1 cyclins are involved in the mechanism of cardiac myocyte hypertrophy induced
      by angiotensin II.
AB  - The importance of the cell cycle in proliferating cells is well known, but little
      is known about the role of cell cycle regulatory proteins in cardiac myocytes,
      which are fully differentiated cells. The present study determined, in vitro, the
      effect of angiotensin II (Ang II) treatment of neonatal rat cardiac myocytes on
      protein levels of cyclins and retinoblastoma gene product (pRb) phosphorylation.
      The role of G1 cyclin/cdk in Ang II-induced cardiac myocyte hypertrophy by
      overexpressing cdk inhibitor p21Cip1/Waf1 or p16INK4a was also examined using
      recombinant adenoviral vectors encoding these genes. Western blot analysis
      revealed that Ang II stimulated cyclin D1, D2, D3 and A protein levels in cardiac
      myocytes. Moreover, Ang II phosphorylated pRb on serine 780, which is known to
      occur in mitotic cells during cell cycle progression. Cultured cardiac myocytes
      treated with Ang II and infected with either control or recombinant adenovirus
      indicated that expression of p21 and p16 inhibited Ang II-induced cardiac myocyte
      hypertrophy, [3H]leucine incorporation into total cellular proteins, and skeletal
      alpha-actin (SK-A) and atrial natriuretic peptide (ANP) mRNA accumulation.
      Control virus had no effects on these parameters. These results suggest that G1
      cyclins play an important role in cardiac myocyte hypertrophy stimulated by Ang
      II.

PMID- 10952157
TI  - 4-aminopyridine inhibits the occurrence of ventricular fibrillation but not
      ventricular tachycardia in the reperfused, P6olated rat heart.
AB  - The 4-aminopyridine (4-AP)-sensitive transient outward current (Ito) has been
      reported to play an important role in the ischemia- or high [Ca2+]o-induced
      reentrant ventricular arrhythmias. However, the role of 4-AP sensitive Ito in
      reperfusion arrhythmia remains unknown. Rat hearts were perfused with Tyrode
      solution (control), and treated with 0.5 micromol/L verapamil, 1 micromol/L
      glibenclamide, 10 micromol/L E-4031 or 2 mmol/L 4-AP. After a 10-min perfusion,
      hearts were subjected to 30-min global ischemia followed by 10-min reperfusion.
      The effects of the ion-channel blockers on the incidence of ventricular
      tachycardia (VT), torsades de pointes (Tdp) and ventricular fibrillation (VF)
      during the reperfusion period were investigated. Verapamil and 4-AP abolished VF
      and Tdp. The incidence of VT was also attenuated by verapamil, but not by 4-AP.
      Glibenclamide and E-4031 (a blocker of a rapidly activating component of delayed
      rectifier K+ current) did not affect the incidence of those tachyarrhythmias.
      Accordingly, (1) the underlying mechanism of VF or Tdp is different from that of
      VT, and (2) 4-AP sensitive Ito is required for the occurrence of reperfusion Tdp
      or VF in the present model.

PMID- 10952158
TI  - Myocardial morphology and cardiac function in rats with renal failure.
AB  - The effects of chronic renal failure on cardiac performance and myocardial
      morphology were studied in rats: 17 with 5/6 nephrectomy (CRF rats) and 12 with
      sham operation (controls). Cardiac function was assessed 8 weeks postoperatively,
      using the Langendorff technique for an isolated working heart model. After the
      hemodynamic study the hearts were fixed for electron and light microscopy. In the
      CRF rats left ventricular systolic pressure was significantly higher at all
      preloads (10-20 cmH2O) and afterloads (70-90 cmH2O), and left ventricular stroke
      work was significantly increased at preload 20 cmH2O with afterloads 70 or 90
      cmH2O. Light microscopy revealed fibronecrotic lesions consisting of fibroblastic
      proliferation with newly formed collagen interposed between or entrapping
      degenerative myocytes. The changes were focally distributed, with perivascular
      accentuation and were most frequent in the basal half of the ventricular wall.
      Electron microscopy of non-necrotic myocytes showed intact myocytes, with
      mitochondria morphometrically similar in the 2 groups, but a significantly lower
      incidence of mitochondrial granules in the CRF rats. Thus 8 weeks of CRF showed
      no cardiac dysfunction associated with the focally distributed fibronecrotic
      myocardial lesions and decrease in mitochondrial granules. The precise mechanism
      of the discrepancy between the morphological change and the cardiac function is
      unclear. One possible explanation may be that because the pathological changes in
      the myocardium were focal or mild to moderate, some compensation mechanism may be
      involved or it may be the turning point of functional change from acute renal
      failure to the chronic state.

PMID- 10952159
TI  - Heart transplantation in children in foreign countries with reference to medical,
      transportation, and financial issues.
AB  - Heart transplantation is increasingly becoming accepted worldwide as therapy for
      end-stage heart failure not only in adult patients but also in pediatric
      practice. The new law in Japan for organ transplantation from brain-dead patients
      was established on 16 October 1998, but there is no definite law or protocol for
      brain death in children under the age of 6 years and children less than 15 years
      of age cannot become donors. These facts make organ transplantation from the
      cadavers of neonates, infants and young children almost impossible in Japan, even
      though there are children who need heart or heart-lung transplantation. The
      present authors have to date transferred 8 patients to the USA or Germany for
      heart transplantation: 4 successfully underwent heart transplantation, but 4 died
      during the waiting period overseas. There are many things to consider; not only
      the medical problems involved in transportation, but also the financial issues
      when transferring patients to other countries. This report details the experience
      with the 8 cases that were transferred overseas for heart transplantation, and
      highlights the problems that need to be considered.

PMID- 10952160
TI  - Hepatitis C virus infection in a patient with dermatomyositis and left
      ventricular dysfunction.
AB  - Hepatitis C virus (HCV) infection is frequently associated with autoimmune
      disease. We present here a case of dermatomyositis manifested as heart failure in
      which HCV was detected from an endomyocardial biopsy sample. HCV infection may
      have contributed to the left ventricular dysfunction in this patient with
      dermatomyositis.

PMID- 10952161
TI  - Unclassified connective tissue disease presenting as cardiac tamponade: a case
      report.
AB  - This report describes a case of cardiac tamponade as the initial manifestation of
      unclassified connective tissue disease (UCTD). A 68-year-old Japanese woman was
      admitted to hospital because of dyspnea and edema. She had undergone a radical
      left mastectomy for the treatment of breast cancer 18 years before. On admission,
      bilateral leg edema, hepatomegaly, and a paradoxical pulse were noted on physical
      examination. The erythrocyte sedimentation rate was elevated and the C-reactive
      protein was 2.8 mg/dl. Antinuclear antibodies and anti-SS-A/Ro antibodies were
      present. The scl-70 and anticentromere antibodies were elevated. Chest
      radiography showed cardiomegaly. Echocardiography revealed a large pericardial
      effusion, but the pericardial fluid did not contain malignant cells or bacteria.
      She did not meet the diagnostic criteria for any known connective tissue
      diseases, so was diagnosed with cardiac tamponade due to UCTD. Prednisolone (30
      mg/day) was administered, which resulted in a gradual resolution of the
      pericardial effusion. Although connective tissue diseases are known to cause
      pericardial effusion, cardiac tamponade as the initial manifestation of the
      disease in the absence of other symptoms is quite rare.

PMID- 10952162
TI  - Dilated phase of hypertrophic cardiomyopathy with mid-ventricular obstruction
      after 20-year follow-up.
AB  - This paper reports a case of dilated phase in hypertrophic cardiomyopathy with
      mid-ventricular obstruction. Following the first cardiac catheterization and
      endomyocardial biopsy, the patient was diagnosed as having hypertrophic
      cardiomyopathy (HCM) with mid-ventricular obstruction. He had been first
      diagnosed at the age of 38 years and was subsequently followed for 20 years.
      Echocardiogram revealed gradually progressive dilatation of the left ventricle,
      associated with disappearance of the mid-ventricular obstruction. The second
      cardiac catheterization and endomyocardial biopsy performed at the age of 58
      disclosed that the patient was in the dilated phase of HCM with a dip-and-plateau
      pattern diastolic pressure trace.

PMID- 10952163
TI  - Isolated cardiac metastasis from sacral chordoma.
AB  - A 64-year-old woman presented with right heart failure caused by a cardiac tumor
      centered in the free wall of the right ventricle, accompanied by pericardial
      effusion. A match between the biopsy specimen and tissue removed 4 years earlier
      resulted in the diagnosis of a cardiac metastasis from a chordoma.
      Immunohistochemical staining was also useful in establishing the diagnosis. To
      alleviate the right ventricular outflow obstruction, a palliative operation was
      planned, resecting the tumor and performing a right ventriculoplasty, which was
      cancelled due to the extent of infiltration of the tumor, and instead a right
      atrium to pulmonary artery shunt was attempted using a vascular prosthesis, only
      to fail due to an inability to maintain blood flow through the prosthesis.
      Presently there are no definitive treatment options available, and some
      palliative chemotherapy is being performed. Single cardiac metastases from a
      chordoma are extremely rare.

PMID- 10952164
TI  - Slowly progressive heart failure due to subepicardial myocardial fibrosis in a
      patient with chronic pericardial effusion.
AB  - A 65-year-old woman was admitted to hospital because of orthopnea. She had been
      followed-up for chronic pericardial effusion detected by echocardiography 10
      years previously. Initial echocardiography showed that the left ventricular
      diastolic diameter (LVDd) was 39 mm and percent fractional shortening (%FS) was
      33.3%. Neither fluid samples nor a pericardial biopsy specimen identified the
      etiology. Cardiac tamponade was not evident, and C-reactive protein and creatine
      kinase values were within normal limits. During follow-up, the %FS decreased
      gradually, but the LVDd remained unchanged. On admission, echocardiography showed
      that the %FS was 12.5% and LVDd was 40 mm. She developed intractable hyponatremic
      heart failure with bilateral pleural effusion. Autopsy findings revealed that
      infiltration of small lymphocytes in the epicardium had penetrated into the
      subepicardial myocardium. The subepicardial myocardium and the interventricular
      septal myocardium were diffusely replaced by fibrosis, which could have induced
      restrictive diastolic heart failure and reduced left ventricular contractility.
      The fibrosis was not detected in the epicardium itself nor the subendocardial
      myocardium. This is the first report describing diffuse subepicardial myocardial
      fibrosis in a patient with chronic pericardial effusion and progressive heart
      failure.

PMID- 10952165
TI  - Demonstration of transient entrainment in monomorphic sustained ventricular
      tachycardia associated with cardiac sarcoidosis.
AB  - A 49-year-old man was referred for further treatment of sustained monomorphic
      ventricular tachycardia (VT) associated with cardiac sarcoidosis. During an
      electrophysiologic study (EP), dl-sotalol suppressed the spontaneous VT and
      prevented induction of VT. However, when predonisolone treatment was started,
      monomorphic VT recurred frequently. To terminate the VT, a temporal pacing lead
      was placed at the apex of the right ventricle, and programmed electrical
      stimulation was attempted from the lead. During the EP study, 2 different
      monomorphic VTs were repetitively induced and both types were able to be
      terminated by rapid ventricular pacing; in one of the VT morphologies, constant
      and progressive fusion was obvious during the ventricular pacing. Some
      monomorphic VTs associated with cardiac sarcoidosis are due to reentry with an
      excitable gap, but the clinical efficacy of EP-guided antiarrhythmic drug
      treatment seems to be less certain during steroid therapy. In the present case, a
      defibrillator device was implanted to prevent a possible arrhythmic event.

PMID- 10952166
TI  - Cardiac tumor biopsy under the guidance of intracardiac echocardiography.
AB  - Transthoracic echocardiography or transesophageal echocardiography is sometimes
      useful in intracardiac tumor biopsy. Intracardiac echocardiography was used as an
      alternative to either of these for performing a biopsy of a right cardiac tumor
      in a 79-year-old woman. The procedure was well tolerated and no complications
      occurred. Histopathological findings and immunohistological staining were
      compatible with the diagnosis of neurogenic sarcoma.

PMID- 10952167
TI  - Acute inferior myocardial infarction and coronary spasm in a patient with an
      anomalous origin of the right coronary artery from the left sinus of valsalva.
AB  - A 56-year-old Japanese woman with an acute inferior myocardial infarction was
      admitted to hospital. Emergency coronary angiography revealed an anomalous origin
      of the right coronary artery from the left sinus of Valsalva, but there was no
      stenosis or thrombus in either the right or left coronary artery. Coronary spasm
      was provoked at the site of the proximal portion of the anomalous coronary
      artery, which was located between the aorta and pulmonary trunk. This was thought
      to be the cause of the myocardial infarction.

PMID- 10952168
TI  - Usefulness of three-dimensional visualization of coronary arteries using electron
      beam computed tomography data with volume rendering.
AB  - Three-dimensional images of the coronary arteries using electron-beam computed
      tomography (EBCT) data with shaded surface rendering makes it possible to achieve
      images easily with a short reconstruction time. However, a lower threshold is
      required to estimate vessel diameters and there is a quantitative problem
      compared with conventional coronary arteriography. In combination with volume
      rendering, EBCT may be useful to detect the normal coronary artery wall, the
      major components of the atherosclerotic plaque (lipid, fibrous connective tissue
      and calcium). EBCT scans offer a new, non-invasive alternative to conventional
      coronary arteriography for diagnosis of coronary artery disease.

PMID- 10952169
TI  - Effect of tibial bone resection on the development of fast- and slow-twitch
      skeletal muscles in foetal sheep.
AB  - To determine if longitudinal bone growth affects the differentiation of fast- and
      slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal
      sheep so that the lower leg was permanently without structural support. At 140
      days (term is approximately 147 days) the contractile properties of whole
      muscles, activation profiles of single fibres and ultrastructure of fast- and
      slow-twitch muscles from the hindlimbs were studied. The contractile and
      activation profiles of the slow-twitch soleus muscles were significantly affected
      by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs
      showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/-
      10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles
      more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ -
      and Sr2+ -activation profiles of skinned fibres similar to those from intact
      hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly
      change whole muscle twitch contraction time, the fatigue profile or the Ca2+ -
      and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an
      increased deposition of glycogen in both soleus and FDL muscles. This study shows
      that the development of the slow-twitch phenotype is impeded in the absence of
      the physical support normally provided by the tibial bone. We suggest that
      longitudinal stretch is an important factor in allowing full expression of the
      slow-twitch phenotype.

PMID- 10952170
TI  - Gelatinase-B (matrix metalloproteinase-9; MMP-9) secretion is involved in the
      migratory phase of human and murine muscle cell cultures.
AB  - The remodelling of connective tissue components is a fundamental requirement for
      a number of pivotal processes in cell biology. These may include myoblast
      migration and fusion during development and regeneration. In other systems,
      similar biological processes are facilitated by secretion of the matrix
      metalloproteinases (MMPs), especially the gelatinases. This study investigated
      the activity of the gelatinases MMP-2 and 9 by zymography on cell conditioned
      media in cultures of cells derived from explants of the human masseter muscle and
      in the murine myoblast cell-line C2C12. Expression of MMP-9 by western blotting
      and TIMP-1, the major inhibitor of MMPs, by northern blotting, during all phases
      of myoblast proliferation, migration, alignment and fusion, was also measured.
      Irrespective of the origin of the cultures, MMP-9 activity was secreted only by
      single cell and pre-fusion cultures whilst MMP-2 activity was secreted at all
      stages as well as by myotubes. The loss of MMP-9 activity was due to the loss of
      MMP-9 protein expression. TIMP-1 mRNA was not detectable at the single cell stage
      but its expression increased as cells progressed through the pre-fusion and post
      fusion stages to reach a maximal in myotube containing cultures. Migration of
      cells derived from human masseter muscle was inhibited, using a specific anti-MMP
      9 blocking monoclonal antibody (6-6B). These data are consistent with the concept
      that regulation of matrix turnover via MMP-9 may be involved in the events
      leading to myotube formation, including migration. Loss of expression of this
      enzyme and expression of TIMP-1 mRNA is associated with myotube containing
      cultures. Consequently, the ratio between MMPs and TIMPs maybe important in
      determining myoblast migration and differentiation.

PMID- 10952171
TI  - Myosin heavy chain profile of equine gluteus medius muscle following prolonged
      draught-exercise training and detraining.
AB  - Fourteen 4-year old Andalusian mares were used to examine the plasticity of
      myosin heavy chain (MHC) composition in horse skeletal muscle with heavy draught
      exercise training and detraining. Seven horses underwent a training programme
      based on carriage exercises for 8 months. Afterwards, they were kept in paddocks
      for 3 months. The remaining seven animals were used as control horses. Three
      gluteus medius muscle biopsies were removed at depths of 20, 40 and 60 mm from
      each horse before (month 0), during the training (months 3 and 8) and after
      detraining (month 11). Myosin heavy chain composition was analysed by
      electrophoresis and immunohistochemically with anti-MHC monoclonal antibodies.
      Fibre areas, oxidative capacity and capillaries were studied histochemically.
      After 8 months of training, MHC-IIX and IIX fibres decreased whereas MHC-I and
      type I and I + IIA fibres increased. Neither MHC-IIA nor the percentage of IIA
      fibres changed when the data were considered as a whole, but the proportion of
      MHC-IIA increased in the superficial region of the muscle after 8 months of
      training. Mean areas of type II fibres were not affected by training and
      detraining, but the cross-sectional of type I fibres increased after 3 month of
      training and not further increases were recorded afterward. The percentage of
      high-oxidative capacity fibres and the number of capillaries per mm2 increased
      with training. Most of these muscular adaptations reverted after detraining.
      These results indicate that long term draught-exercise training induces a
      reversible transition of MHC composition in equine muscle in the order IIX -->
      IIA --> I. The physiological implication of these changes is an impact on the
      velocity of shortening and fatigue resistance of muscle fibres.

PMID- 10952172
TI  - Effect of adrenaline on the post-tetanic potentiation in mouse skeletal muscle.
AB  - We report the influence of adrenergic stimulation on the amplitude and time
      course of post-tetanic potentiation of twitch contraction. This was complemented
      by measurements of the peak of [Ca2+]i transients in twitches and of the level of
      myosin light chain 2 (LC2) phosphorylation, before, 20 and 300 s after the
      conditioning tetanus. Soon after the tetanus, twitch potentiation and increases
      of LC2 phosphorylation and of [Ca2+]i peak were similar in control conditions and
      in the presence of adrenaline. In control conditions, twitch potentiation, LC2
      phosphorylation and [Ca2+]i peak returned to, or close to, pre-tetanic values in
      300 s. On the contrary, in the presence of adrenaline, twitch potentiation and
      LC2 phosphorylation were partially or fully maintained respectively, while the
      increase of [Ca2+]i peak was not. This situation allowed us to analyse the
      relative contributions of elevated LC2 phosphorylation and [Ca2+]i peak in the
      twitch post-tetanic potentiation phenomenon. Moreover, it was shown that the
      increase of LC2 phosphorylation (up to 0.5 mol P/mol LC2) affected neither the
      kinetic parameters of the twitch nor the maximal velocity of shortening. It is
      proposed that the maintenance of LC2 phosphorylation in the presence of
      adrenaline results from the inhibition of myosin light chain phosphatase. This
      could be achieved through the production of the active, phosphorylated form of
      the inhibitor-1, an endogenous inhibitor, which binds to the catalytic sub-units
      common to class 1 protein phosphatases.

PMID- 10952173
TI  - The effects of anti-hypertensive therapy on the structural, mechanical and
      metabolic properties of the rat aorta.
AB  - The vascular system exhibits altered growth, calcium responses and metabolism
      during hypertension. To relate such changes, we compared histological, tension
      and metabolic responses in the aorta from 32-week-old spontaneously hypertensive
      rats (SHRs), normotensive Wistar-Kyoto (WKY) rats, and SHRs treated with
      Verapamil (V) and ACE-inhibitor, Trandolapril (T) as well as a combination of the
      two treatments (C). Vascular hypertrophy was apparent in the SHRs. Contractile
      responses induced by 50 mmol/1 KCl and 2.5 mmol/1 Ca2+ were significantly lower
      in the SHR (64.4 mN/mm2 vs. 49.2 mN/mm2), but an associated increase in Ca2+ 
      sensitivity (EC50 of extracellular Ca2+ (mumol/1): SHR, 456 vs. WKY, 616)
      normalised tension generating ability. All treatments led to significant
      decreases in blood pressure, although only T and C treated animals became
      normotensive with concomitant normalisation of vascular hypertrophy. An increase
      in oxygen consumption was apparent in the SHR aorta, which was associated with
      significant differences in the activities of key metabolic enzymes. Anti
      hypertensive treatment normalised many of the metabolic parameters, with the C
      therapy being the most efficacious. We conclude that the treatment of
      hypertension by combined therapy leads to a better normalisation of structural,
      contractile, and metabolic parameters in the SHR, than either treatment alone and
      that metabolic changes with the pathology are resolved with appropriate therapy.

PMID- 10952174
TI  - Lack of coordinated changes in metabolic enzymes and myosin heavy chain isoforms
      in regenerated muscles of trained rats.
AB  - We investigated training-induced changes in biochemical properties and myosin
      heavy chain (MHC) composition of regenerated (cardiotoxin-injected) plantaris
      muscles (PLA) in rats either maintained sedentary (S, n = 9) or endurance trained
      on a treadmill over a 8-week period (T, n = 7). Both endurance training and
      regeneration altered the pattern of fast MHC expression. An analysis of the two
      way interaction between training and regeneration showed that the relative
      content of type IIa MHC was affected (P < 0.05). The 140% increase in type IIa
      MHC observed in regenerated PLA from T rats compared with nontreated muscle of S
      rats, exceeded the 102% increase resulting from the combination of regeneration
      alone (26%) and training alone (61%). A similar interaction between training and
      regeneration was shown for the percentage of fibres expressing either type IIa or
      type lIb MHC (P < 0.05). In contrast, a significant increase in the citrate
      synthase (CS) activity was shown in PLA as a result of endurance training,
      without specific effect of regeneration. Furthermore, training-induced changes in
      CK and LDH isoenzyme distribution occurred to a similar extent in regenerated and
      non-treated PLA muscles, and thus did not follow the changes in MHC isoforms. An
      increase in the mitochondrial CK isozyme activity (mi-CK) was shown in both non
      treated and previously degenerated PLA muscles (123 and 117%, P < 0.01,
      respectively), without specific effect of regeneration. The ratio of mi-CK to CS
      activity, an estimate of the mitochondrial specific activity of mi-CK was
      significantly increased by training (P < 0.02) and decreased by regeneration (P <
      0.05). Taken together, these data suggest that while training and regeneration
      have cumulative effects on the pattern of fast MHC expression, the training
      induced changes in the energy metabolism shown in mature non-treated myofibres
      are similar to those observed in regenerated fibres.

PMID- 10952175
TI  - Modifications of Ca2+ transport induced by glutathione in sarcoplasmic reticulum
      membranes of frog skeletal muscle.
AB  - The Ca2+ transport across the membrane of vesicles purified from the sarcoplasmic
      reticulum (SR) of frog skeletal muscle is modified by raising the concentration
      of the reduced form of glutathione (GSH). Passive release of Ca2+ is inhibited
      through the direct action of GSH on ryanodine receptors while active uptake is
      increased by a dose-dependent stimulation of Ca2+ pumps (Ca2+ -ATPase). These
      effects are physiological since the concentrations of GSH utilised (0.01-10.0 mM)
      are compatible with the in vivo concentration of this antioxidant. They are
      independent of the external Ca2+ concentration and are specific for the reduced
      form of glutathione, since the disulphide form (GSSG) or other GSH-derivatives do
      not induce these effects.

PMID- 10952176
TI  - Oxygenation and perfusion of rabbit tibialis anterior muscle subjected to
      different patterns of electrical stimulation.
AB  - Dual amperometric microelectrodes were used to measure local pO2 and perfusion at
      multiple sites in the fast-twitch tibialis anterior muscles of anaesthetized
      rabbits. Six muscles were stimulated continuously at 10, 5, or 2.5 Hz. For all
      three frequencies, perfusion declined to about 50% of resting levels and
      recovered after stimulation. These changes corresponded to a rise followed by a
      fall in extracellular pO2. The highest levels of pO2 were reached during
      stimulation at 10 Hz. Eight muscles were stimulated tetanically at 100 Hz for 200
      ms with duty cycles that were varied between 1.3 and 20.0%. Perfusion rose to 8.7
      +/- 2.0 ml s(-1) 100 g(-1) at a duty cycle of 5% and declined with further
      increases in duty cycle. pO2 was depressed for duty cycles less than 10% but rose
      above resting levels at higher duty cycles. It is suggested that the paradoxical
      combination of elevated pO2 and depressed perfusion is attributable to
      stimulation conditions that exceed the oxygen transport capacity of a fast
      muscle.

PMID- 10952178
TI  - Do cross-bridges contribute to the tension during stretch of passive muscle? A
      response.

PMID- 10952177
TI  - Influence of microtubules on vascular smooth muscle contraction.
AB  - Microtubules are ubiquitous in eukaryotic cells and play key roles in many
      cellular activities. The purpose of this study was to investigate the influence
      of microtubules on vascular smooth muscle contraction. Quantitative
      immunocytochemical analysis of rat aortic tissue revealed that, relative to the
      control group, colchicine (15 muM, 90 min) and nocodazole (15 muM, 90 min)
      decreased the microtubule density by 40-50% while taxol (10 muM, 90 min)
      increased the microtubule density by 33%. Isometric contraction studies
      demonstrated that both colchicine and nocodazole caused an upward shift in the
      phenylephrine (10(-8) to 10(-5) M) dose-response curve while taxol caused no
      significant change when compared to the control group. Potassium chloride (30 mM)
      induced 55 +/- 5% P0 contraction in DMSO treated vessel rings. The active tension
      increased to 73 +/- 5% P0 and 71 +/- 6% P0 after pretreatment of the aortic rings
      with colchicine or nocodazole, respectively. Taxol did not cause a significant
      change in the active tension (56 +/- 7% P0). These results indicate that
      microtubule depolymerization enhances isometric contraction of vascular smooth
      muscle and this enhanced contraction is not receptor dependent. Pretreatment of
      the aortic rings with an inhibitor of nitric oxide synthase (NOS) (Nomega-nitro-L
      arginine) did not change the increased contractile response to phenylephrine due
      to microtubule depolymerization suggesting that this phenomenon is not mediated
      by endothelium dependent relaxation.

PMID- 10952179
TI  - Spinal dysraphism: a review of neuroradiological features with embryological
      correlations and proposal for a new classification.
AB  - Our purpose was to review the neuroradiological features of spinal dysraphism and
      to correlate them with clinical findings and up-to-date embryological theory. We
      also aimed to formulate a working classification which might prove useful in
      clinical practice. We reviewed series of 986 children referred to our Spina
      Bifida Centre in the past 24 years. There were 353 children with open spinal
      (OSD) and 633 with closed (skin-covered) spinal (CSD) dysraphism. By far the most
      common open abnormality was myelomeningocele, and all patients with OSD had a
      Chiari II malformation. CSD was categorised clinically, depending on the presence
      of a subcutaneous mass in the back. CSD with a mass mainly consisted of lipomas
      with dural defects and meningoceles, and accounted for 18.8 % of CSD. CSD without
      a mass were simple (tight filum terminale, intradural lipoma) or complex (split
      cord malformations, caudal regression). Our suggested classification is easy to
      use and to remember and takes into account clinical and MRI features; we have
      found it useful and reliable when making a preoperative neuroradiological
      diagnosis in clinical practice.

PMID- 10952180
TI  - Chronological changes in nonhaemorrhagic brain infarcts with short T1 in the
      cerebellum and basal ganglia.
AB  - Our purpose was to investigate nonhaemorrhagic infarcts with a short T1 in the
      cerebellum and basal ganglia. We carried out repeat MRI on 12 patients with
      infarcts in the cerebellum or basal ganglia with a short T1. Cerebellar cortical
      lesions showed high signal on T1-weighted spin-echo images beginning at 2 weeks,
      which became prominent from 3 weeks to 2 months, and persisted for as long as 14
      months after the ictus. The basal ganglia lesions demonstrated slightly high
      signal from a week after the ictus, which became more intense thereafter. Signal
      intensity began to fade gradually after 2 months. High signal could be seen at
      the periphery until 5 months, and then disappeared, while low or isointense
      signal, seen in the central portion from day 20, persisted thereafter.

PMID- 10952181
TI  - Multifocal low-signal brain lesions on T2*-weighted gradient-echo imaging.
AB  - Multifocal small low-signal lesions on T2*-weighted gradient-echo (GE) MRI are
      reported to be common in the brain of hypertensive patients. We examined factors
      associated with these lesions. For one year, we routinely obtained T2*-weighted
      GE images (TR 1000 TE 30 ms, flip angle = 20 degrees) in all adult patients (314)
      who underwent brain MRI in our hospital, using a 1.5 T superconducting magnet.
      Patients with multifocal small low-signal lesions with a known or presumed
      pathogenesis or any condition which may cause intracerebral haemorrhage, such as
      brain tumours, were excluded from further analysis. Thus, 191 cases remained (104
      men and 87 women; age, 62.8+/-11.0 years, range, 30-89 years). The overall
      prevalence of multifocal small low-signal lesions on the GE images was 15.2%
      (29/191); they were commonly in the cerebral white matter and basal ganglia. They
      were detected in 12 (52.2%) of the 23 patients with prior symptomatic brain
      hemorrhage, 12 (20.7%) of the 58 with prior symptomatic infarcts, and only five
      (4.5%) of 110 without a prior stroke. Logistic regression analysis indicated that
      multifocal small low-signal lesions were significantly correlated with a
      symptomatic acute brain haemorrhage (odds ratio, 13.17), chronic hypertension
      (4.00) and a symptomatic acute infarct (3.71). The association with symptomatic
      acute brain haemorrhage suggests that this finding may represent subclinical
      microhaemorrhage. The diagnostic potential of this finding to identify
      individuals at risk of symptomatic intracerebral haemorrhage may require further
      investigation.

PMID- 10952182
TI  - Dural enhancement in pituitary macroadenomas.
AB  - We describe the normal dural enhancement patterns of the sellar region and
      determine whether the duramater is affected by pituitary macroadenomas. Dural
      enhancement appeared to be usually abnormal in 20 patients with pituitary
      macroadenoma compared with 20 control patients, mainly at the planum sphenoidale
      and carotid sulcus. However dural changes are subtle and their recognition
      requires knowledge of the normal enhancement patterns. Dural changes, reported in
      a variety of inflammatory and infectious dural diseases and after surgery, are
      not specific and may be also seen in pituitary macroadenomas.

PMID- 10952183
TI  - Neuroradiological characteristics of pineocytoma and pineoblastoma.
AB  - We reviewed neuroradiological images in two histologically proven cases of
      pineocytoma and three of pineoblastoma to delineate the characteristic features
      of these rare tumours. CT revealed isodense or slightly hyperdense masses with
      central or peripheral calcification; enhancement with contrast medium tended to
      be homogeneous in pineocytomas and heterogeneous in pineoblastomas. In the
      pineocytomas, T1-weighted images revealed rounded, sometimes or slightly
      lobulated low-signal masses with strong, homogeneous contrast enhancement. Their
      margin was clear, without invasion of adjacent structures. In the pineoblastomas,
      however, T1-weighted images revealed multilobulated tumours with heterogeneous
      contrast enhancement. All three pineoblastomas had poorly defined margins with
      adjacent structures such as the posterior thalamus or corpus callosum, suggesting
      a more invasive nature. T2-weighted images revealed nonspecific high signal
      lesions in all five cases.

PMID- 10952184
TI  - In vivo 1H-magnetic resonance spectroscopy of the spinal cord in humans.
AB  - Magnetic resonance spectroscopy (MRS) has been used in a variety of conditions
      affecting the central nervous system. Until now, only the brain has been studied,
      and spectroscopy of the spinal cord has not been previously reported. During the
      past 12 months, we have been experimenting with MRS of the cervical spinal cord
      of healthy volunteers. We present this technique, its current limitations, and
      possible future technological improvements and potential applications.

PMID- 10952185
TI  - Radiographic findings in tuberculosis of the calvarium.
AB  - We reviewed the pattern of involvement of the calvarium by tuberculosis (TB) in
      five patients and the role of imaging in its management. Four patients presented
      with localised scalp swelling and one with generalized seizures. Radiographs
      revealed lucent lesions with minimal surrounding sclerosis in the frontal (2),
      parietal (2) and occipital (1) bones. CT showed lesions involving the entire
      thickness of the calvarium and accompanying contrast-enhancing soft tissue. The
      patient presenting with seizures had a ring-enhancing lesion in the parietal lobe
      in addition to the extra-axial lesions. Although radiographs in all cases
      demonstrated calvarial TB, CT showed the extent of the defect, involvement of
      adjacent soft tissues, and in one case an intra-axial lesion. Radiographs suffice
      for follow-up of these patients.

PMID- 10952186
TI  - Calcification of intracranial vessels in neurocysticercosis.
AB  - We report calcification of intracranial vessels in neurocysticercosis.
      Calcification was observed in the middle cerebral arteries in two patients, and
      the circle of Willis in two others. The patients with middle cerebral artery
      calcification underwent CT with inhaled stable xenon and an area of mild
      hypoperfusion was observed in the ipsilateral cerebral hemisphere.

PMID- 10952187
TI  - MRI in human immunodeficiency virus-associated cerebral vasculitis.
AB  - Cerebral ischaemia caused by inflammatory vasculopathies has been described as
      complication of human immunodeficiency virus (HIV) infection. Imaging studies
      have shown ischaemic lesions and changes of the vascular lumen, but did not allow
      demonstration of abnormalities within the vessel wall itself. Two HIV-infected
      men presented with symptoms of a transient ischaemic attack. Initial MRI of the
      first showed no infarct; in the second two small lacunar lesions were detected.
      In both cases, multiplanar 3-mm slice contrast-enhanced T1-weighted images showed
      aneurysmal dilatation, with thickening and contrast enhancement of the wall of
      the internal carotid and middle cerebral (MCA) arteries. These findings were
      interpreted as indicating cerebral vasculitis. In the first patient the
      vasculopathy progressed to carotid artery occlusion, and he developed an infarct
      in the MCA territory, but then remained neurologically stable. In the second
      patient varicella zoster virus (VZV) infection was the probable cause of
      vasculitis. The clinical deficits and vasculitic MRI changes regressed with
      antiviral and immunosuppressive therapy.

PMID- 10952188
TI  - Spontaneous intracranial hypotension: use of unenhanced MRI.
AB  - We report a case of spontaneous intracranial hypotension diagnosed with
      unenhanced cranial MRI, showing laminar subdural fluid and engorgement of the
      hypophysis and perisellar sinuses. Cerebrospinal fluid pressure was low. MRI was
      normal after resolution of symptoms. Prior reports emphasise the enhancing
      pachymeninges seen in this syndrome. We maintain that, when subdural collections
      and perisellar engorgement are detected on unenhanced MRI in the proper clinical
      setting, contrast enhancement may not be necessary for the diagnosis.

PMID- 10952189
TI  - Rathke's cleft cyst associated with hypophysitis: MRI.
AB  - We report a symptomatic Rathke's cleft cyst associated with hypophysitis in a 61
      year-old woman. We demonstrate the MRI features and discuss the pathophysiology.
      To the best of our knowledge this is the first description of a Rathke's cleft
      cyst shrinking after high-dose steroid therapy.

PMID- 10952190
TI  - Spontaneous dissection of the anterior inferior cerebellar artery.
AB  - A patient presented with the clinical features of a brain stem infarct. MRI
      confirmed changes of infarction but also revealed an unusual lesion in the left
      cerebellopontine angle cistern. The evolution of this lesion on MRI, together
      with angiographic changes, indicated a dissecting aneurysm of the left anterior
      inferior cerebellar artery, a previously unreported phenomenon. The presentation,
      causes and diagnosis of intracranial dissection are discussed.

PMID- 10952191
TI  - A ruptured dissecting aneurysm of the anterior radiculomedullary artery caused by
      vertebral angiography.
AB  - We report here a 54-year-old man with an aneurysm arising on a cervical anterior
      radiculomedullary artery. The aneurysm ruptured just after vertebral angiography
      for a vascular anomaly of the brain, and it appeared to be fusiform, with
      thrombosis following angiography. Considering the sequential radiological studies
      and clinical course, it was assumed to be a dissecting aneurysm caused by the
      angiography. MRI showed severe swelling of the cervical spinal cord and an
      infarct in the territory of the anterior spinal artery. The mechanism of this
      rare complication is discussed.

PMID- 10952192
TI  - Virtual endoscopy of the inner ear and the auditory canal.
AB  - To assess the role of virtual endoscopy (VE) in the examination of intracisternal
      structures and of the inner ear, we studied the anatomy of the labyrinth and
      internal auditory canal using the original CT slices and VE on the unaffected
      side in three female and three male patients, age range 3-46 years, with
      contralateral retrocochlear hearing loss. We also examined seven patients with
      different pathological findings. VE was performed using an advanced
      postprocessing program with high-resolution 3D data sets of CT (1-1.5 mm
      thickness, pitch 1.25) and MRI-CISS-3D (constructive interference in steady
      state) images of the basal cisterns (1.5 T, slice thickness 0.7-1 mm). VE
      provides an endoscopic-like view from a given point within the basal cisterns of
      vessels and nerves (on MRI) or of the structures of the inner ear (on CT). The
      complex anatomy and pathological changes in the inner ear can be faithfully
      shown. The main advantage is not basic diagnostic information but demonstration
      of topographically complex situations, such as the canalicular system of the
      inner ear, for discussion, preoperative planning and teaching.

PMID- 10952193
TI  - Comparative genomics and evolutionary dynamics of Saccharomyces cerevisiae Ty
      elements.
AB  - The availability of the complete genome sequence of Saccharomyces cerevisiae
      provides the unique opportunity to study an entire genomic complement of
      retrotransposons from an evolutionary perspective. There are five families of
      yeast retrotransposons, Ty1-Ty5. We have conducted a series of comparative
      sequence analyses within and among S. cerevisiae Ty families in an effort to
      document the evolutionary forces that have shaped element variation. Our results
      indicate that within families Ty elements vary little in terms of both size and
      sequence. Furthermore, intra-element 5'-3' long terminal repeat (LTR) sequence
      comparisons indicate that almost all Ty elements in the genome have recently
      transposed. For each family, solo LTR sequences generated by intra-element
      recombination far outnumber full length insertions. Taken together, these results
      suggest a rapid genomic turnover of S. cerevisiae Ty elements. The closely
      related Ty1 and Ty2 are the most numerous elements in the genome. Phylogenetic
      analysis of full length insertions reveals that reverse transcriptase mediated
      recombination between Ty1 and Ty2 elements has generated a number of hybrid Ty1/2
      elements. These hybrid Ty1/2 elements have similar genomic structures with
      chimeric LTRs and chimeric TYB (pol) genes. Analysis of the levels of
      nonsynonymous (Ka) and synonymous (Ks) nucleotide variation indicates that Ty1
      and Ty2 coding regions have been subject to strong negative (purifying)
      selection. Distribution of Ka and Ks on Ty1, Ty2 and Ty1/2 phylogenies reveals
      evidence of negative selection on both internal and external branches. This
      pattern of variation suggests that the majority of full length Ty1, Ty2 and Ty1/2
      insertions represent active or recently active element lineages and is consistent
      with a high level of genomic turnover. The evolutionary dynamics of S. cerevisae
      Ty elements uncovered by our analyses are discussed with respect to selection
      among elements and the interaction between the elements and their host genome.

PMID- 10952194
TI  - Is the evolution of transposable elements modular?
AB  - The evolution of transposable element structures can be analyzed in populations
      and species and by comparing the functional domains in the main classes of
      elements. We begin with a synthesis of what we know about the evolution of the
      mariner elements in the Drosophilidae family in terms of populations and species.
      We suggest that internal deletion does not occur at random, but appears to
      frequently occur between short internal repeats. We compared the functional
      domains of the DNA and/or amino acid sequences to detect similarities between the
      main classes of elements. This included the gag, reverse transcriptase, and
      envelope genes of retrotransposons and retroviruses, and the integrases of
      retrotransposons and retroviruses, and transposases of class II elements. We find
      that each domain can have its own evolutionary history. Thus, the evolution of
      transposable elements can be seen to be modular.

PMID- 10952195
TI  - Molecular paleontology of transposable elements from Arabidopsis thaliana.
AB  - We report results of a comprehensive computer-assisted analysis of new
      transposable elements (TEs) from Arabidopsis thaliana. Our analysis revealed
      several previously unknown pogo- and En/Spm-like families and two novel
      superfamilies of DNA transposons, Arnold and Harbinger. One of the En/Spm-like
      families (Atenspm) was found to be involved in generating satellite arrays in
      paracentromeric regions. Of the two superfamilies reported, Harbinger is
      distantly related to bacterial IS5-like insertion elements, and Arnold contains
      DNA transposons without terminal inverted repeats (TIRs), which were never
      reported in eukaryotes before. Furthermore, we report a large number of young and
      diverse copia-like autonomous and nonautonomous retroelements and discuss their
      potential evolutionary relationship with mammalian retroviruses. The A. thaliana
      genome harbors copia-like retroelements which encode a putative env-like protein
      reported previously in the SIRE-1 retrotransposon from soybean. Finally, we
      demonstrate a nonrandom chromosomal distribution of the most abundant A. thaliana
      TEs clustered in the first half of chromosome II, which includes the centromeric
      region. The families of TEs from A. thaliana are relatively young, extremely
      diverse and much smaller than those from mammalian genomes. We discuss the
      potential factors determining similarities and differences in the evolution of
      TEs in mammals and A. thaliana.

PMID- 10952196
TI  - Human L1 retrotransposition: insights and peculiarities learned from a cultured
      cell retrotransposition assay.
AB  - Long Interspersed Nuclear Elements (L1s or LINEs) are the most abundant
      retrotransposons in the human genome, and they comprise approximately 17% of DNA.
      L1 retrotransposition can be mutagenic, and deleterious insertions both in the
      germ-line and in somatic cells have resulted in disease. Recently, an assay was
      developed to monitor L1 retrotransposition in cultured human cells. This assay,
      for the first time, now allows for a systematic study of L1 retrotransposition at
      the molecular level. Here, I will review progress made in L1 biology during the
      past three years. In general, I will limit the discussion to studies conducted on
      human L1s. However, interesting parallels to rodent L1s and other non-LTR
      retrotransposons also will be discussed.

PMID- 10952197
TI  - Structure, functionality, and evolution of the BARE-1 retrotransposon of barley.
AB  - The BARE-1 retrotransposon is a major, active component of the genome of barley
      (Hordeum vulgare L.) and other Hordeum species. Copia-like in its organization,
      it consists of 1.8-kb long terminal repeats bounding an internal domain of 5275
      bp which encodes a predicted polyprotein of 1301 residues. The polyprotein
      contains the key residues, structural motifs, and conserved regions associated
      with retroviral and retrotransposon GAG, aspartic proteinase, integrase, reverse
      transcriptase, and RNaseH polypeptides. BARE-1 is actively transcribed and
      translated. As part of our effort to understand the evolution and function of
      BARE-1, we have examined its copy number and localization. Full-length members of
      the BARE-1 family constitute 2.8% of the barley genome. Globally, they are
      dispersed throughout the genome, excepting the centromeric, telomeric, and NOR
      regions. Locally, BARE-1 occurs more commonly in repetitive DNA than in coding
      regions, forming clusters of nested insertions. Both barley and other Hordeum
      genomes contain a high proportion of BARE-1 solo LTRs. New techniques have been
      developed which exploit the insertion site polymorphism generated by BARE-1
      integration to produce molecular markers for breeding, biodiversity, and mapping
      applications.

PMID- 10952198
TI  - Retrolycl-1, a member of the tntl retrotransposon super-family in the
      Lycopersicon peruvianum genome.
AB  - Retrotransposons are ubiquitous mobile genetic elements that transpose through an
      RNA intermediate. One of the best known plant retrotransposon, Tnt1, was isolated
      from tobacco and showed an extensive distribution in the Nicotiana genus. We
      investigated the presence of related sequences in the Lycopersicon genus, another
      member of the Solanaceae family. Hybridization experiments performed using Tnt1
      probes indicated that homologous sequences were present in all Lycopersicon
      species, indicating that these Tnt1-related sequences, that we named Retrolyc1,
      are distributed throughout the Lycopersicon genus. Different distribution
      patterns were detected between species, demonstrating a potential use of
      Retrolyc1 elements as molecular markers. An incomplete Retrolyc1 sequence, that
      we named Retrolyc1-1, was isolated from an L. peruvianum genomic library.
      Retrolyc1-1 shows extensive homology with Tnt1 sequences except in the LTR U3
      region. Since this region is known to be involved in the control of
      transcription, this strongly suggests the existence of different patterns of
      regulation for Tnt1 and Retrolyc1 elements. The study of these two elements
      within the Solanaceae family may provide interesting models for retrotransposon
      evolution within this group and transmission in host genomes.

PMID- 10952199
TI  - Retrotransposon 1731 in Drosophila melanogaster changes retrovirus-like
      expression strategy in host genome.
AB  - Earlier related to parasitic elements, retrotransposons of eukaryotes have been
      demonstrated to participate in general cell processes such as chromosome repair
      and evolution of gene expression (Teng et al., 1996; McDonald, 1993). Here, we
      report the existence of two classes of genomic copies of retrotransposon 1731
      with different expression strategies, one of which might be driven by natural
      selection. The first class uses conventional translational frameshifting known to
      ensure expression of reverse transcriptase (RT) open reading frame (ORF),
      depending on the efficiency of frameshifting. The bulk of genomic copies are
      related to the second class where the frameshift is prevented as a result of the
      substitution of a rare codon recognising rare tRNA by a codon preferred by host
      genome, whereas the RT ORF is restored by downstream single nucleotide deletion.
      We suggest that natural selection has driven the switching of 1731 expression
      strategy from retrovirus-like to the fusion-ORF expression. This observation is
      in accordance with the detection in testes of fused Gag-RT polypeptide encoded by
      1731. The abundance of RT in testes may serve for normal development of host
      tissue.

PMID- 10952201
TI  - Phylogenetic evidence for Ty1-copia-like endogenous retroviruses in plant
      genomes.
AB  - SIRE-1 is a multi-copy, Ty1-copia-like retroelement family found in the genome of
      Glycine max. A sequenced SIRE-1 genomic copy has an uninterrupted ORF that can be
      translated into a gag-pol polyprotein, followed by an unprecedented second ORF
      whose conceptual translation yielded a theoretical protein predicted to possess
      many of the same secondary structural elements found in mammalian retroviral
      envelope proteins. Similar, but clearly pseudogenic, envelope-like sequences were
      recovered from conceptual translations of 10 Arabidopsis GenBank accessions. All
      were associated with identifiable Ty1-copia-like retroelements. Phylogenetic
      analysis of the adjacent ribonuclease H regions from these sequences and three
      similarly endowed elements, two from maize and one from tomato, indicate that the
      14 elements constitute a monophyletic group distinct from several closely related
      plant Ty1-copia-like elements in which pol is immediately followed by a
      downstream LTR. The conservation of identifiable env-like gene features suggests
      that these plant elements are endogenous retroviruses whose ancestors were
      acquired from animal vectors. The finding that the env and env-less retroelements
      identified in this study form distinct lineages does not support the hypothesis
      that horizontal transmission of retrotransposons is sponsored by ancestral
      infectious retroviruses that subsequently lost all traces of env genes.

PMID- 10952200
TI  - Regulatory potential of nonautonomous mariner elements and subfamily crosstalk.
AB  - Two naturally occurring nonautonomous mariner elements were tested in vivo for
      their ability to down-regulate excision of a target element in the presence of
      functional mariner transposase. The tested elements were the peach element
      isolated from Drosophila mauritiana, which encodes a transposase that differs
      from the autonomous element Mos1 in four amino acid replacements, and the DTBZ1
      element isolated from D. teissieri, which encodes a truncated protein consisting
      of the first 132 residues at the amino end of the normally 345-residue
      transposase. We provide evidence that the protein from the peach element does
      interact to down-regulate wildtype transposase, indicating that at least some
      nonautonomous elements in natural populations that retain their open reading
      frame may play a regulatory role. In contrast, our tests reveal at most a weak
      interaction between transposase from the autonomous Mos1 element and the
      truncated protein from DTBZ1, and none between Mos1 transposase and that from the
      distantly related mariner-like element Himar1 identified in the horn fly
      Haematobia irritans. Hence, the extent of regulatory crosstalk between mariner
      like elements may be limited to closely related ones. The evolutionary
      implications of these results are discussed.

PMID- 10952202
TI  - Evidence for genomic regulation of the telomeric activity in Drosophila
      melanogaster.
AB  - The structural integrity of TART elements has been used as reporter of
      instability at chromosomal ends in numerous Drosophila stocks and over time in an
      unstable stock. The results show that telomeric activity is a regulated process
      that may differ between the stocks as well as over time within a stock.

PMID- 10952203
TI  - How valuable are model organisms for transposable element studies?
AB  - Model organisms have proved to be highly informative for many types of genetic
      studies involving 'conventional' genes. The results have often been successfully
      generalized to other closely related organisms and also, perhaps surprisingly
      frequently, to more distantly related organisms. Because of the wealth of
      previous knowledge and their availability and convenience, model organisms were
      often the species of choice for many of the earlier studies of transposable
      elements. The question arises whether the results of genetic studies of
      transposable elements in model organisms can be extrapolated in the same ways as
      those of conventional genes? A number of observations suggest that special care
      needs to be taken in generalizing the results from model organisms to other
      species. A hallmark of many transposable elements is their ability to amplify
      rapidly in species genomes. Rapid spread of a newly invaded element throughout a
      species range has also been demonstrated. The types and genomic copy numbers of
      transposable elements have been shown to differ greatly between some closely
      related species. Horizontal transfer of transposable elements appears to be more
      frequent than for nonmobile genes. Furthermore, the population structure of some
      model organisms has been subject to drastic recent changes that may have some
      bearing on their transposable element genomic complements. In order to initiate
      discussion of this question, several case studies of transposable elements in
      well-studied Drosophila species are presented.

PMID- 10952204
TI  - Transposable elements and genome evolution: the case of Drosophila simulans.
AB  - Drosophila simulans presents a large variation in copy number among various
      transposable elements (TEs) and among natural populations for a given element.
      Some elements such as HMS beagle, blood, flea, tirant, coral, prygun, jockey, F,
      nomade and mariner are absent in most populations, except in one or two which
      have copies on their chromosome arms. This suggests that some TEs are being
      awakened in D. simulans and are in the process of invading the species while it
      is colonizing the world. The elements 412 and roo/B104 present a wide insertion
      polymorphism among D. simulans populations, but only the 412 copy number follows
      a temperature cline. One population (Canberra from Australia) has a very high
      copy number for the 412 element and for many other TEs as well, indicating that
      some populations may have lost control of some of their TEs. While the 412
      transposition rate is similar in all populations, its transcription level
      throughout developmental stages varies with populations, depending on copy
      number. Populations with 412 copy number higher than 10-12 exhibit co
      suppression, while the expression in populations with lower numbers depends on
      the insertion location. All these results suggest genomic invasions by 412 and
      other TEs during the worldwide spread of the D. simulans species.

PMID- 10952205
TI  - Horizontal transfer of non-LTR retrotransposons in vertebrates.
AB  - Since their discovery in family Bovidae (bovids), Bov-B LINEs, believed to be
      order-specific SINEs, have been found in all ruminants and recently also in
      Viperidae snakes. The distribution and the evolutionary relationships of Bov-B
      LINEs provide an indication of their origin and evolutionary dynamics in
      different species. The evolutionary origin of Bov-B LINE elements has been shown
      unequivocally to be in Squamata (squamates). The horizontal transfer of Bov-B
      LINE elements in vertebrates has been confirmed by their discontinuous
      phylogenetic distribution in Squamata (Serpentes and two lizard infra-orders) as
      well as in Ruminantia, by the high level of nucleotide identity, and by their
      phylogenetic relationships. The direction of horizontal transfer from Squamata to
      the ancestor of Ruminantia is evident from the genetic distances and
      discontinuous phylogenetic distribution of Bov-B LINE elements. The ancestral
      snake lineage (Boidae) has been recognized as a possible donor of Bov-B LINE
      elements to Ruminantia. The timing of horizontal transfer has been estimated from
      the distribution of Bov-B LINE elements in Ruminantia and the fossil data of
      Ruminantia to be 40-50 mya. The phylogenetic relationships of Bov-B LINE elements
      from the various Squamata species agrees with that of the species phylogeny,
      suggesting that Bov-B LINE elements have been stably maintained by vertical
      transmission since the origin of Squamata in the Mesozoic era.

PMID- 10952206
TI  - Sure facts, speculations, and open questions about the evolution of transposable
      element copy number.
AB  - Transposable elements (TEs) are sequences capable of multiplying in their host's
      genome. They survive by increasing copy numbers due to transpositions, and
      natural selection washes them out because hosts with heavier loads of TEs have
      lower fitness. The available phylogenetic evidence supports the view that TEs
      have existed in living organisms for hundreds of millions of years. A fundamental
      question facing the field is how can an equilibrium be attained between
      transposition and selection which allows these parasitic genetic elements to
      persist for such a long time period? To answer this question, it is necessary to
      understand how the rate of TE transposition is controlled and to describe the
      mechanisms with which natural selection opposes TE accumulation. Perhaps the best
      models for such a study are copia and gypsy retrotransposons in Drosophila. Their
      average rate of transposition in nature is between 10(-5) - 10(-4) transpositions
      per copy per generation. Unlike nature, transposition rates vary widely, from
      zero to 10(-2), between laboratory lines. This variability in transposition rate
      is controlled by host genes. It is probable that in nature TE site heterogeneity
      is caused by frequent transpositions in rare flies with permissive alleles, and
      no transpositions happen in the rest of flies. The average rate of TE
      transposition in nature may thus depend on the frequency of permissive alleles,
      which is a function of the rate of mutation from restrictive to permissive
      alleles, the mechanism and the strength of selection opposing TE multiplication,
      and population size. Thus, evolution of the frequency of permissive alleles of
      genes controlling transposition must be accounted for to understand evolution of
      TE copy numbers.

PMID- 10952207
TI  - Transposon dynamics and the breeding system.
AB  - The selfish DNA hypothesis predicts that natural selection is responsible for
      preventing the unregulated build up of transposable elements in organismal
      genomes. Accordingly, between-species differences in the strength and
      effectiveness of selection against transposons should be important in driving the
      evolution of transposon activity and abundance. We used a modeling approach to
      investigate how the rate of self-fertilization influences the population dynamics
      of transposable elements. Contrasting effects of the breeding system were
      observed under selection based on transposon disruption of gene function versus
      selection based on element-mediated ectopic exchange. This suggests that the
      comparison of TE copy number in organisms with different breeding systems may
      provide a test of the relative importance of these forces in regulating
      transposon multiplication. The effects of breeding system also interacted with
      population size, particularly when there was no element excision. The strength
      and effectiveness of selection against transposons was reflected not only in
      their equilibrium abundance, but also in the per-site element frequency of
      individual insertions and the coefficient of variation in copy number. These
      results are discussed in relation to evidence on transposon abundance available
      from the literature, and suggestions for future data collection.

PMID- 10952208
TI  - Recently integrated human Alu repeats: finding needles in the haystack.
AB  - Alu elements undergo amplification through retroposition and integration into new
      locations throughout primate genomes. Over 500,000 Alu elements reside in the
      human genome, making the identification of newly inserted Alu repeats the genomic
      equivalent of finding needles in the haystack. Here, we present two complementary
      methods for rapid detection of newly integrated Alu elements. In the first
      approach we employ computational biology to mine the human genomic DNA sequence
      databases in order to identify recently integrated Alu elements. The second
      method is based on an anchor-PCR technique which we term Allele-Specific Alu PCR
      (ASAP). In this approach, Alu elements are selectively amplified from anchored
      DNA generating a display or 'fingerprint' of recently integrated Alu elements.
      Alu insertion polymorphisms are then detected by comparison of the DNA
      fingerprints generated from different samples. Here, we explore the utility of
      these methods by applying them to the identification of members of the smallest
      previously identified subfamily of Alu repeats in the human genome termed Ya8.
      This subfamily of Alu repeats is composed of about 50 elements within the human
      genome. Approximately 50% of the Ya8 Alu family members have inserted in the
      human genome so recently that they are polymorphic, making them useful markers
      for the study of human evolution.

PMID- 10952209
TI  - Phylogenetic signals from point mutations and polymorphic Alu insertions.
AB  - Allelic frequency data derived from five polymorphic Alu insertion loci and five
      point mutation polymorphic loci were compared to determine their ability to infer
      phylogenetic relationships among human populations. While point mutation
      polymorphisms inferred a monophyletic Caucasian clade that is corroborated by
      other studies, these data failed to support the generally accepted monophyly of
      Orientals with native Americans. In addition, there is less statistical bootstrap
      support for the maximum-likelihood tree derived from the point mutation
      polymorphisms as compared to those generated from either the Alu insertion data
      or the combined Alu insertion + point mutation data. The Alu data and the
      combined Alu insertion + point mutation data inferred a monophyletic relationship
      among the Oriental and native American populations. The Alu insertion data and
      the combined Alu insertion + point mutation data also displayed two separate,
      well defined, tight clusters of the Caucasian and the Oriental + native American
      populations which was not inferred from the point mutation data. These findings
      indicate greater phylogenetic information contained in Alu insertion frequencies
      than in allelic frequencies derived from point-mutations.

PMID- 10952210
TI  - Transposable elements as the key to a 21st century view of evolution.
AB  - Cells are capable of sophisticated information processing. Cellular signal
      transduction networks serve to compute data from multiple inputs and make
      decisions about cellular behavior. Genomes are organized like integrated computer
      programs as systems of routines and subroutines, not as a collection of
      independent genetic 'units'. DNA sequences which do not code for protein
      structure determine the system architecture of the genome. Repetitive DNA
      elements serve as tags to mark and integrate different protein coding sequences
      into coordinately functioning groups, to build up systems for genome replication
      and distribution to daughter cells, and to organize chromatin. Genomes can be
      reorganized through the action of cellular systems for cutting, splicing and
      rearranging DNA molecules. Natural genetic engineering systems (including
      transposable elements) are capable of acting genome-wide and not just one site at
      a time. Transposable elements are subject to regulation by cellular signal
      transduction/computing networks. This regulation acts on both the timing and
      extent of DNA rearrangements and (in a few documented cases so far) on the
      location of changes in the genomes. By connecting transcriptional regulatory
      circuits to the action of natural genetic engineering systems, there is a
      plausible molecular basis for coordinated changes in the genome subject to
      biologically meaningful feedback.

PMID- 10952211
TI  - Transposable elements as activators of cryptic genes in E. coli.
AB  - The concept of transposable elements (TEs) as purely selfish elements is being
      challenged as we have begun to appreciate the extent to which TEs contribute to
      allelic diversity, genome building, etc. Despite these long-term evolutionary
      contributions, there are few examples of TEs that make a direct, positive
      contribution to adaptive fitness. In E. coli cryptic (silent) catabolic operons
      can be activated by small TEs called insertion sequences (IS elements). Not only
      do IS elements make a direct contribution to fitness by activating cryptic
      operons, they do so in a regulated manner, transposing at a higher rate in
      starving cells than in growing cells. In at least one case, IS elements activate
      an operon during starvation only if the substrate for that operon is present in
      the environment. It appears that E. coli has managed to take advantage of IS
      elements for its own benefit.

PMID- 10952212
TI  - Drosophila telomeres: two transposable elements with important roles in
      chromosomes.
AB  - Telomeres in Drosophila melanogaster are composed of multiple copies of two
      retrotransposable elements, HeT-A and TART instead of the short DNA repeats
      generated by telomerase in most organisms. Transpositions of HeT-A and TART yield
      arrays of repeats larger and more irregular than the repeats produced by
      telomerase; nevertheless, these transpositions are, in principle, equivalent to
      the telomere-building action of telomerase. Both telomerase and transposition of
      HeT-A and TART extend chromosomes by RNA-templated addition of specific
      sequences. We have proposed that HeT-A has evolved from genes encoding telomerase
      components. Although both HeT-A and TART share some novel features, TART probably
      has a different origin from HeT-A. HeT-A and TART are clearly identifiable as non
      long terminal repeat (non-LTR) retrotransposons. Both telomere elements transpose
      only to the ends of chromosomes (apparently to any chromosome end in D.
      melanogaster) and each contains a large segment of untranslated sequence. HeT-A
      and TART are the first examples of transposable elements with a clear role in
      chromosome structure. This has interesting implications for the evolution of both
      chromosomes and transposable elements. The finding also raises the possibility
      that other transposable elements with bona fide roles in the cell will be
      detected, not only in Drosophila, but also in other organisms.

PMID- 10952213
TI  - Molecular domestication--more than a sporadic episode in evolution.
AB  - Transposable elements are short but complex pieces of DNA or RNA containing a
      streamlined minimal-genome with the capacity for its selfish replication in a
      foreign genomic environment. Cis-regulatory sections within the elements
      orchestrate tempo and mode of TE expression. Proteins encoded by TEs mainly
      direct their own propagation within the genome by recruitment of host-encoded
      factors. On the other hand, TE-encoded proteins harbor a very attractive
      repertoire of functional abilities for a cell. These proteins mediate excision,
      replication and integration of defined DNA fragments. Furthermore, some of these
      proteins are able to manipulate important host factors by altering their original
      function. Thus, if the host genome succeeds in domesticating such TE-encoded
      proteins by taming their 'anarchistic behavior,' such an event can be considered
      as an important evolutionary innovation for its own benefit. In fact, the
      domestication of TE-derived cis-regulatory modules and protein coding sections
      took place repeatedly in the course of genome evolution. We will present
      prominent cases that impressively demonstrate the beneficial impact of TEs on
      host biology over evolutionary time. Furthermore, we will propose that molecular
      domestication might be considered as a resumption of the same evolutionary
      process that drove the transition from 'primitive genomes' to 'modern' ones at
      the early dawn of life, that is, the adaptive integration of a short piece of
      autonomous DNA into a complex regulatory network.

PMID- 10952214
TI  - Genomes were forged by massive bombardments with retroelements and
      retrosequences.
AB  - Retroposition is an efficient route to move coding regions around the genome 'in
      search' of novel regulatory elements and to shotgun regulatory elements into the
      genome 'in search' of new target genes. The templates for such retrogenes are
      mRNAs, and for regulatory retronuons (nuon = any definable nucleic acid sequence)
      usually small non-mRNAs (snmRNAs). An example in support of the 'master gene'
      model for SINEs (short interspersed repetitive elements) is provided with
      neuronal BC1 RNA. Furthermore, an alternative explanation of LINE (long
      interspersed repetitive elements) involvement in the generation of SINEs is
      given. I will also argue that the status of transposable elements with respect to
      the host resembles more symbiosis than parasitiasis and that host defense is
      often lenient as if even to 'tolerate or support' retronuons. Finally the paradox
      of evolution's lack of foresight and the future exaptive use of retronuons is
      being dealt with by referring to W.F. Doolittle's 'Hierarchical Approaches to
      Genome Evolution'.

PMID- 10952215
TI  - Sectorial mutagenesis by transposable elements.
AB  - Transposable elements (TEs) generate insertions and cause other mutations in the
      genomic DNA. It is proposed that during co-evolution between TEs and eukaryotic
      genomes, an optimal path of the insertion mutagenesis is determined by the
      surviving TEs. These TEs can become semi-permanently established, chromatin
      regulated 'source' or 'mutator genes', responsible for targeting insertion
      mutations to specific chromosomal regions. Such mutations can manifest themselves
      in non-random distribution patterns of interspersed repeats in eukaryotic
      chromosomes. In this paper we discuss specific models,examples and implications
      of optimized mutagenesis in eukaryotes.

PMID- 10952216
TI  - Cell-surface area codes: mobile-element related gene switches generate precise
      and heritable cell-surface displays of address molecules that are used for
      constructing embryos.
AB  - We present an updated area code hypothesis supporting the proposal that cell
      surface display of seven-transmembrane olfactory receptors, protocadherins and
      other cell surface receptors provide codes that enable cells to find their
      correct partners as they sculpture embryos. The genetic mechanisms that program
      the expression of such displays have been largely unknown until very recently.
      However, increasing evidence now suggests that precise developmental control of
      the expression of these genes during embryogenesis is achieved in part by
      permanent and heritable changes in DNA. Using the developing immune system as a
      model, we discuss two different types of developmentally programmed genetic
      switches, each of which relies on recombination mechanisms related to mobile
      elements. We review new evidence suggesting the involvement of mobile element
      related switch mechanisms in the generation of protocadherin molecules, and their
      possible involvement in the control of expressions of olfactory receptors. As
      both recombinase and reverse transcriptase mechanisms play a role in the
      switching of the immunoglobulin genes, we searched the databases of expressed
      sequence tags (dbEST) for expression of related genes in other tissues. We
      present data revealing that transposases and reverse transcriptases are widely
      expressed in most tissues. We also searched these databases for expression of env
      (envelope) gene products, stimulated by provocative results suggesting that these
      molecules might function as cellular address receptors. We found that env genes
      are also expressed in large numbers in normal human tissues. One must assume that
      these three different types of mobile-element-related messenger RNA molecules
      (transposases, reverse transcriptases, and env proteins) are expressed for use in
      functions of value in the various tissues and have been preserved in the genome
      because of their selective advantages. We conclude that it is possible that many
      specific cell lineage decisions are made and remembered by means of genetic
      switches similar to those that control the immunoglobulin and protocadherin and,
      probably, the seven transmembrane/olfactory gene families. We also conclude that
      complex genetic programs utilizing mobile-element-related genes program these
      events.

PMID- 10952217
TI  - Transposable DNA elements and life history traits: II. Transposition of P DNA
      elements in somatic cells reduces fitness, mating activity, and locomotion of
      Drosophila melanogaster.
AB  - Some transposable DNA elements in higher organisms are active in somatic cells,
      as well as in germinal cells. What effect does the movement of DNA elements in
      somatic cells have on life history traits? It has previously been reported that
      somatically active P and mariner elements in Drosophila induce genetic damage and
      significantly reduce lifespan. In this study, we report that the movement of P
      elements in somatic cells also significantly reduces fitness, mating activity,
      and locomotion of Drosophila melanogaster. If other elements cause similar
      changes in life history traits, it is doubtful if transposable DNA elements
      remain active for long in somatic cells in natural populations.

PMID- 10952218
TI  - Host defenses to parasitic sequences and the evolution of epigenetic control
      mechanisms.
AB  - The analysis of transgene silencing effects in plants and other eukaryotic
      organisms has revealed novel mechanisms of epigenetic regulation that are based
      on recognition of nucleic acid sequence homology. These homology-dependent gene
      silencing phenomena are characterized by an inverse relationship between copy
      number of a particular sequence and expression levels. Depending on whether
      promoter regions or transcribed sequences are repeated, silencing occurs at the
      transcriptional or post-transcriptional level, respectively. Different silencing
      effects involving DNA-DNA or RNA-DNA associations in the nucleus, and RNA-RNA
      interactions in the cytoplasm appear to reflect distinct host defense responses
      to parasitic sequences, including transposable elements (TEs), viroids and RNA
      viruses. Natural epigenetic phenomena that resemble transgene silencing effects
      often involve endogenous genes comprising recognizable TE sequences or
      rearrangements generated by TEs and can thus be interpreted in terms of host
      defense systems. A genome defense that inactivates TEs by methylation might have
      been recruited during evolution to regulate the transcription of plant and
      vertebrate genes that contain remnants of TE insertions in promoter regions.

PMID- 10952219
TI  - Sex brings transposons and genomes into conflict.
AB  - Given that transposons are so abundant in mammalian genomes, it is natural to
      assume that through their maintenance the host gains some net benefit. This need
      not be true; sexual reproduction allows a transposon to go to fixation if the
      reduction in fitness of the host is anything less than two-fold. Obligate
      outcrossing sexual reproduction therefore favors the evolution of aggressive
      transposons, which in turn select for the evolution of host mechanisms that
      suppress transposon activity. Hosts that have asexual or self-fertilizing
      generations will select for transposons that are more benign and self-limiting
      than those of obligate sexuals, and obligate asexuals and uniparental organelle
      genomes will be free of active transposons if these impose any fitness penalty.
      We are interested in host mechanisms that suppress transposons in sexuals and
      have found that mammals (all of which are obligate sexuals) control their large
      populations of potentially active retroposons by methylating the five position of
      cytosine residues within promoter elements. This causes strong transcriptional
      repression and assembly of the affected sequences into the condensed state.
      Methylation also causes permanent inactivation in the germline by driving C-->T
      transition mutations at methylated sites. It is now known that methylation
      remains in place for the large majority of the life of germ cells and is
      essential for control of the very large transposon burden. There is pressure on
      transposons to evolve mechanisms that overcome host suppression, and over
      evolutionary time, the balance swings back and forth between parasite and host.
      The ability of the mammalian genome to absorb and accumulate additional
      transposons has caused the amount of reverse transcriptase coding sequence in the
      human genome to far exceed the sum total of all cellular coding sequence. While
      transposons could, in principle, contribute functions useful to the host, the
      fact that asexual species and uniparental organelle genomes lack transposons is
      strong evidence that transposons have a net deleterious effect even in genomes
      that might be thought to require an additional source of plasticity. The
      abundance of transposons in many genomes cannot be taken as evidence of a
      mutualistic relationship, and the conflict between transposons and genomes may
      have actually retarded rather than accelerated evolution. It is suggested that
      the relationship between sex and transposons is as follows: (i) Obligate sexuals
      will tend to harbor aggressive transposons limited largely by host suppressive
      mechanisms, which in mammals involve methylation of transposon promoters. (ii)
      The aggressiveness of transposons in facultative sexuals and self-fertilizing
      sexuals will be in part self-limited and will be proportional to the relative
      frequency of asexual and outcrossing sexual generations. (iii) Obligate asexuals
      arid organelles transmitted in a uniparental manner will have no active
      transposons if these have a net negative effect on host fitness.

PMID- 10952220
TI  - Large differences in laboratory utilisation between hospitals in Sweden.
AB  - There are large differences in the use of laboratory tests between hospitals in
      Sweden. These differences are not only due to differences between the patients
      treated but also to differences in practice. Use of laboratory test seems to
      reflect local traditions to a large extent. These large variations in practice
      are not compatible with the objective of providing care on equal terms and reduce
      the cost-effectiveness of clinical chemistry. Recently, several intervention
      studies have been performed in Sweden with the aim to optimise the use of
      clinical chemistry tests in primary care. The results show that it is possible to
      reduce the cost in primary care by SEK 100 million per year while increasing the
      clinical usefulness. This constitutes approximately 10% of the total cost for
      clinical chemistry tests in primary care. It should also be possible to reduce
      the cost for clinical chemistry tests in secondary and tertiary care. Hospitals
      order more tests than primary care and the potential savings are thus greater. We
      have studied the ordering habits for eleven Swedish hospitals. The comparison was
      made in the form of ratios between related laboratory tests to reduce the effects
      of differences in size between the studied laboratories. The large variation
      between hospitals indicates that a continuous discussion between the clinicians
      and the laboratories could reduce the cost. We have used the figures from the
      comparison and calculated the potential savings for seven frequently used tests.
      The potential yearly saving in Sweden for these tests is approximately SEK 150
      million.

PMID- 10952221
TI  - Development of a method for rapid quantitation of amino acids by liquid
      chromatography-tandem mass spectrometry (LC-MSMS) in plasma.
AB  - A new analytical method has been developed and is proposed for the rapid
      determination of eighteen common amino acids, including tryptophan, in plasma and
      dried blood spots, by liquid chromatography coupled with ionspray tandem mass
      spectrometry. Potentially the method can include other amino acids and can be
      used for the diagnosis of metabolic disease. The use of the ionspray tandem mass
      spectrometry approach permits extremely rapid chromatographic separation of all
      amino acids requiring less than four minutes for the analysis of each sample,
      after a simple sample preparation procedure. The chromatographic separation of
      the analytes was achieved using a CN normal phase column and a
      water/acetonitrile/trifluoroacetic acid mobile phase at flow rate of 1 ml/min.
      The mass spectrometer was operated in multiple reaction monitoring mode, where
      each analyte had its own unique precursor and product ion setting. The
      quantitative analysis of amino acids was achieved using as internal standards
      just two representative isotopically labeled amino acids: D4-Ala and D5-Phe.
      Calibration is made externally by using aqueous solutions with the same labelled
      amino acids as internal standards. The high specificity of tandem mass
      spectrometry coupled with a fast chromatographic process is suitable for the
      rapid and reliable assay of metabolically significant amino acids. The liquid
      chromatography-tandem mass spectrometry method is more effective than other
      published tandem mass spectrometry methods at distinguishing isobaric amino acids
      like Leu, Ile and HO-Pro and certainly far more rapid than HPLC or ion-exchange
      chromatographic methods.

PMID- 10952222
TI  - Adhesion molecule behavior during rejection and infection episodes after heart
      transplantation.
AB  - In cardiac transplant recipients the release of soluble cellular adhesion
      molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1) and E-Selectin into serum is pronounced during immune
      activation. It is uncertain whether there is a specific pattern of release during
      infection or cardiac allograft rejection. In a prospective study, 30 consecutive
      cardiac allograft recipients were followed for a median period of 11.4 months
      (range 1-34). Soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1) and soluble E
      Selectin (sE-Selectin) were measured in addition to acute phase proteins (C
      reactive protein, alpha1-antitrypsin), complement factors (C3, C4) and beta2
      microglobulin. The measured serum levels were correlated with the clinical status
      of the transplant recipient: 1) uneventful clinical status; 2) asymptomatic
      infection; 3) symptomatic infection and 4) rejection. Forty age-matched healthy
      subjects served as controls. Six days before biopsy-proven cardiac allograft
      rejection sICAM-1-release started to increase (p < 0.05) as compared to
      uneventful clinical status. The peak concentration of sICAM-1 was measured three
      days before rejection. On the day of rejection, serum concentrations of sICAM-1
      (p < 0.001) and sVCAM-1 (p < 0.05) were increased, whereas sE-Selectin was not
      markedly elevated. In symptomatic infections, the serum concentrations of sICAM-1
      (p < 0.001) and sVCAM-1 (p < 0.05) were elevated at the day of diagnosis and both
      parameters reached peak levels three days after onset of chemotherapy. In
      multivariate analysis soluble adhesion molecules only weakly discriminated
      between rejection and infection (sensitivity: 13%, specificity: 95%). Although,
      in combination with routine blood parameters the discriminatory power could be
      improved (sensitivity: 85%, specificity: 85%) the clinical utility of these
      markers in non-invasive monitoring is limited.

PMID- 10952223
TI  - The activity of class I and II alcohol dehydrogenase isoenzymes in the sera of
      patients with liver tumours.
AB  - We have measured the activity of class I and II alcohol dehydrogenase isoenzymes
      in the sera of patients with liver tumours, using class-specific fluorogenic
      naphthaldehydes as substrates. The activity of the tested isoenzymes was
      unchanged in primary tumours and significantly increased (class I) in metastatic
      liver tumours. The total enzyme activity was also increased (3-fold) in this
      group of patients. The elevated activity of class I isoenzymes in secondary
      tumours seems to be caused by the enzyme released from primary cells originating
      in the other organs, but increased total enzyme activity measured with
      chromogenic substrates may be proof of the presence of other classes of
      isoenzymes. These results show that the elevated class I isoenzymes and total
      enzyme activity in the sera of patients with liver tumours may indicate the
      metastatic origin of these tumours.

PMID- 10952225
TI  - Concentration of Lp(a) and other apolipoproteins in predialysis, hemodialysis,
      chronic ambulatory peritoneal dialysis and post-transplant patients.
AB  - Serum levels of lipids, lipoprotein(a) Lp(a) and other apolipoproteins were
      determined in 47 predialysis patients, 40 hemodialysis (HD) patients, 39 chronic
      ambulatory peritoneal dialysis (CAPD) patients, 11 patients after kidney
      transplantation and 47 healthy subjects as reference group. The predialysis, HD,
      and CAPD patients had disturbances in the concentration of serum triglyceride
      (TG), high density lipoprotein (HDL)-cholesterol, apolipoprotein AI (apoAI),
      total apoCIII, apoCIII present in the particles without apoB (apoCIII non B), and
      Lp(a) and HDL-cholesterol, low density lipoprotein (LDL)-cholesterol/HDL
      cholesterol, HDL-cholesterol/apoAI, apoAI/apoB, and apoAI/apoCIII ratios.
      Predialysis patients had significantly lower concentrations of HDL-cholesterol
      and total apoE levels than CAPD patients and total apoE level than HD patients.
      Moreover, both HD and CAPD patients had significantly increased levels of apoB
      containing apoE (apoB:E) and apoB containing apoCIII (apoB:CIII). The
      concentrations of serum TG, total cholesterol, LDL-cholesterol, apoB, Lp(a) in
      CAPD patients were statistically higher than in HD patients. The patients after
      transplantation demonstrated normalization of lipid and lipoprotein parameters
      and lipoprotein ratios except serum levels of TG, total apoCIII, apoCIII non B
      and the apoAI/apoCIII ratio. We concluded that abnormal lipid and lipoprotein
      concentrations in patients with uremia may be the cause of their high risk of
      atherosclerosis, but posttransplant patients exhibited improved levels of serum
      lipids, Lp(a) and other lipoprotein parameters and lipoprotein composition, which
      could be an index of decreased atherogenic status.

PMID- 10952224
TI  - Association between PON1 L/M55 polymorphism and plasma lipoproteins in two
      Canadian aboriginal populations.
AB  - Serum paraoxonase circulates on a subfraction of high density lipoproteins and
      appears to use phospholipids on both low and high density lipoprotein particles
      as a physiological substrate. This functional relationship could explain the
      reported associations between common variation in the PON1 gene--at codons 55 and
      192--and phenotypes related to atherosclerosis and lipoprotein metabolism. We
      evaluated associations between plasma lipoproteins and PON1 L/M55, PON1 Q/R192
      and PON2 A/G148 polymorphisms in samples from two Canadian aboriginal
      populations, namely the Oji-Cree and the Inuit. In diabetic Oji-Cree, we found
      that carriers of PON1 M55 had a higher mean plasma triglyceride concentration
      than non-carriers. In non-diabetic Oji-Cree, we found that carriers of PON1 M55
      had higher mean plasma concentrations of total and low density lipoporetein
      cholesterol and apo B than non-carriers. In Inuit, we found that carriers of PON1
      M55 had higher mean plasma concentrations of total and low density lipoprotein
      cholesterol than non-carriers. The other polymorphic markers were not associated
      with variation in any plasma lipoprotein trait. Thus, the PON1 M55 allele
      appeared to be associated with deleterious changes in the plasma lipoprotein
      profile from two independent Canadian aboriginal samples. These results suggest
      that common variation in PON1 codon 55 is associated with variation of
      intermediate traits in plasma lipoprotein metabolism in aboriginal Canadians.

PMID- 10952226
TI  - Remnant-like particle cholesterol levels in Korean patients with coronary artery
      disease and non-insulin dependent diabetes mellitus.
AB  - Several studies have provided evidence that the remnants of lipoproteins may be
      the atherogenic components of triglyceride-rich lipoproteins. The purpose of this
      study was to investigate whether the remnant-like particle cholesterol (RLP-C) is
      an independent risk factor for coronary artery disease (CAD) and non-insulin
      dependent diabetes mellitus (NIDDM) in the Korean population and to explore the
      relationship between RLP-C and other biochemical markers as well as the
      apolipoprotein (apo) E genotypes. Lipid and lipoproteins including RLP-C and apo
      E genotypes were analyzed in 98 normal adults (control group), 68 patients with
      CAD (CAD group), 88 patients with NIDDM (DM group), and 19 patients with both CAD
      and NDDM (CAD + DM group). RLP-C levels were significantly higher in the DM (p <
      0.0001), CAD (p = 0.0012) and the CAD + DM groups (p = 0.0184) than in the
      controls. To determine which variable could discriminate most effectively and
      independently among the different groups, stepwise linear discriminant analysis
      was performed for all the variables that showed p < 0.15 by univariate analysis.
      RLP-C was selected as an independent discriminator between the control and
      patient groups. RLP-C levels showed a strong positive correlation with
      trigylceride levels in the control, CAD and DM groups (r = 0.783, r = 0.610 and r
      = 0.746, respectively). In overall groups, apo epsilon4 and epsilon2 carrier
      genotypes showed a significant increase in RLP-C levels compared with epsilon3/3
      wild-type (p = 0.0085). After adjusting for the effect of apo E genotypes, a
      significant increase of the RLP-C levels in the disease groups remained. In
      conclusion, RLP-C was determined to be an independent risk factor in Korean
      patients with CAD and NIDDM and showed a strong correlation with triglyceride
      levels. We suggest that the increased cardiovascular risk associated with the
      epsilon4 and epsilon2 allele may be mediated by more atherogenic RLP-C.

PMID- 10952227
TI  - Red blood cell osmotic fragility confidence intervals: a definition by
      application of a mathematical model.
AB  - The red blood cell osmotic fragility test is based on the measure of the
      resistance of red blood cells to lysis as a function of decreasing NaCl
      concentration. Up to now, several methods have been used for recording these
      data, but for the first time, the human red blood cell osmotic fragility
      confidence interval using the Orcutt mathematical model was determined. The
      absorbance of the hemoglobin measured at 540 nm, released by the red blood cells
      of 40 healthy adult individuals, was fitted to the equation Absorbance=p3 erfc
      ([NaCl] - p1/p2); p3 measures one half the absorbance produced by maximum red
      blood cell hemolysis, p1 is the [NaCl] producing 50% red blood cell hemolysis,
      and p2 is the dispersion in [NaCl] producing red blood cell hemolysis. Confidence
      intervals (mean+/-SD) for the three parameters were as follows: p1=4.2718+/
      0.1848; p2=0.1947+/-0.0391, and p3=0.5568+0.0426. The usefulness of this osmotic
      fragility data analysis method using two pathological samples (beta-thalassemia
      minor and hereditary spherocytosis) was demonstrated. Parameters of the fitted
      data were compared with those obtained by the conventional recording method of
      Beutler.

PMID- 10952228
TI  - Assessment of iron status with a new fully automated assay for transferrin
      receptor in human serum.
AB  - Serum transferrin receptor is considered as a reliable marker of iron status
      particularly when iron deficiency is associated with chronic disorders such as
      inflammation, infection or malignancy. The present study aims to illustrate the
      performances of a new fully automated assay using immunonephelometry. The intra
      and between-assay precision was found to be very good (CVs < 4%). In healthy
      subjects there was no statistically significant difference between men and women.
      With a cut-off of 1.76 mg/l for diagnosing iron deficiency either alone or
      combined with anemia of chronic diseases, the sensitivity and specificity were
      respectively 82% and 96.8%. Unlike conventional biochemical and hematological
      tests, soluble transferrin receptor was unaffected by confounding pathologies. In
      genetic hemochromatosis the concentration of soluble transferrin receptor was
      mostly decreased due to the regulatory effect of iron intracellular level. Our
      study confirms the reliability of soluble transferrin receptor for the assessment
      of iron status. It is now possible to assay soluble transferrin receptor,
      ferritin and transferrin on the same apparatus within 15 minutes.

PMID- 10952229
TI  - Alterations in laboratory test results during adjuvant breast cancer treatment.
AB  - An increasing number of women is treated with adjuvant cyclophosphamide,
      methotrexate and 5-fluorouracil therapy for breast cancer. The effects of the
      chemotherapy on many laboratory tests are, however, inadequately known. This
      study investigates the effects of the treatment on various laboratory tests.
      Fifteen premenopausal women receiving adjuvant cyclophosphamide, methotrexate and
      5-fluorouracil chemotherapy and optional radiotherapy were included in the study.
      Common hormonal, biochemical, hematological, protein and lipid laboratory tests
      were taken serially during a 10-month follow-up. Twelve women became amenorrheic.
      Their serum follicle stimulating hormone and luteinising hormone concentrations
      increased accordingly. Other serum hormones (testosterone, androstenedione, sex
      hormone-binding globulin, prolactin, dehydroepiandrosterone sulfate, cortisol,
      parathyroid hormone and thyroid hormones) changed only slightly. Hemoglobin
      concentration and white blood cell count decreased slightly. Serum alanine
      aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase,
      angiotensin-converting enzyme, amylase, glucose, potassium, phosphate, urea and
      triglycerides concentrations increased slightly whereas serum bilirubin,
      haptoglobin, and immunoglobulin A and M decreased slightly. Serum alpha1
      antitrypsin fluctuated around the baseline concentration. Other test results
      remained at their pretreatment concentrations. With the exception of increases in
      serum gonadotrophins, the changes observed were slight and the mean
      concentrations remained within reference limits. Therefore, cyclophosphamide,
      methotrexate and 5-fluorouracil adjuvant treatment is unlikely to complicate the
      diagnosis of other diseases.

PMID- 10952230
TI  - Assessment of CA 15.3, CEA and TPA concentrations during monitoring of breast
      cancer.
AB  - The variability of the tumor markers cancer antigen (CA) 15.3, carcinoembryonic
      antigen (CEA) and tissue polypeptide antigen (TPA) during steady state
      concentrations and the rate of increase during progression is described. One
      hundred and ninety-two patients were monitored during first-line chemotherapy for
      metastatic breast cancer and during follow-up. Blood specimens were sampled
      approximately every four weeks. Steady state concentrations were registered for
      77 (CA 15.3), 96 (CEA), and 127 (TPA) patients with below cutoff level values and
      for 28 (CA 15.3), 25 (CEA), and 11 (TPA) patients with above cutoff level values.
      Clinical and marker progression was registered for 75 (CA 15.3), 62 (CEA), and 57
      (TPA) patients. The coefficients of total variation of steady state
      concentrations (comprising the intra- and interassay analytical imprecision and
      the within subject biological variation) were higher below (14.9% CA 15.3, 15.4%
      CEA, 25.9% TPA) than above cutoffs (9.6% CA 15.3,6.0% CEA, 19.9% TPA). The
      variability was similar for CA 15.3 and CEA but higher for TPA. During
      progression the rates of increase in concentrations were similar for CA 15.3
      (0.0257) and CEA (0.0214) and lower than for TPA (0.0346). Our data indicate that
      criteria for assessment of sequential tumor marker concentrations should consider
      the marker in question, the steady state variability, the cutoff value, and the
      rate of increase during disease progression.

PMID- 10952231
TI  - Evaluation of a newly available biochemical analyzer: the Olympus AU 600.
AB  - The performance of the Olympus AU 600, a newly available open multiparametric
      analyzer, available for routine biochemical analysis of biological samples, was
      evaluated. The analytical and technical performance of the apparatus and the
      quality of the Olympus reagents were both examined in a single site study.
      Electrolyte concentrations were determined with patented ion-selective
      electrodes; substrate concentrations and enzyme activities were determined by
      spectrophotometric measurement after coloured reaction or UV detection-based
      reactions. The protocol of the evaluation and the acceptability criteria were
      those recommended by the French Society for Clinical Biology. For the parameters
      studied, the upper limits of linearity were equal to or higher than those claimed
      by the manufacturer. The CV values for within-run and between-run precision were
      lower than the target values with few exceptions. The comparison study gave
      satisfactory results for most of the parameters. Only expected interferences
      occurred. In summary, the results obtained for the 25 parameters studied and the
      characteristics of the apparatus were satisfactory. The analyzer is rapid (800 to
      1200 tests per hour) and easy to use. In addition, the analyzer complies with
      good analytical practice and its flexibility enables users to plan work according
      to local laboratory constraints.

PMID- 10952232
TI  - Association between apolipoprotein E alleles and autoantibodies against oxidised
      low-density lipoprotein.

PMID- 10952233
TI  - ALP isoenzyme separation in type 1 Gaucher disease.

PMID- 10952234
TI  - Volume-sensitive purinergic signaling in human hepatocytes.
AB  - BACKGROUND/AIMS: Purinergic signaling potentially contributes to many liver
      functions. Therefore, the purpose of these studies was to characterize adenosine
      5'-triphosphate (ATP) release from human hepatocytes, and to determine the role
      of extracellular ATP in the autocrine regulation of Cl- permeability and cell
      volume homeostasis. METHODS: Release of ATP (luciferase-luciferin assay), Cl-
      currents (whole-cell patch clamp), and cell volume (Coulter Multisizer) were
      measured in human hepatocytes within 12 h of isolation. RESULTS: Hepatocyte
      swelling increased bioluminescence from basal values of 11.21+/-0.45 to 178.29+/
      44.49 and 492.15+/-89.41 arbitrary light units following 20 and 40% buffer
      dilutions, respectively (p<0.001), representing an increase in extracellular ATP
      from approximately 10 to >300 nM. Whole-cell Cl- currents activated during
      exposure to hypotonic buffer (15% less mosmol, 126.34+/-36.49 pA/pF) and ATP (10
      microM, 71.92+/-15.48 pA/pF) exhibited outward rectification, time-dependent
      inactivation at depolarizing potentials, and sensitivity to the anion channel
      blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). Removal of
      extracellular ATP (apyrase) prevented volume-sensitive current activation.
      Exposure to hypotonic buffer (30% less mosmol) increased mean relative volume to
      1.092+/-0.004 by 2.5 min, and volume recovery (1.019+/-0.002 by 30 min) was
      abolished by NPPB, apyrase, and the P2 receptor antagonist suramin. CONCLUSIONS:
      These findings indicate that human hepatocytes exhibit constitutive and volume
      dependent ATP release, which is a critical determinant of membrane Cl-
      permeability and cell volume regulation. ATP release may represent an
      extracellular signaling pathway that couples the cellular hydration state to
      important hepatic functions.

PMID- 10952235
TI  - Enhancement of retrovirus-mediated gene transfer to rat liver in vivo by infusion
      of hepatocyte growth factor and triiodothyronine.
AB  - BACKGROUND/AIMS: Gene transfer using recombinant Moloney murine leukemia viruses
      (rMoMuLV) requires mitosis of the target cell. Previously, we and others have
      used partial hepatectomy for induction of hepatocellular proliferation for gene
      transfer to the liver in vivo by exsanguineous perfusion with rMo-MuLV. We
      hypothesized that induction of hepatocellular proliferation by combined
      administration of two hepatocellular mitogens, hepatocyte growth factor (HGF) and
      triiodothyronine (T3), should permit rMo-MuLV-mediated gene transfer into liver
      without invasive approaches. METHODS: HGF (1 mg/kg) was perfused continuously
      into the portal vein of Wistar male rats and T3 (2 mg/kg) was injected
      subcutaneously. Twenty-four hours after injecting HGF and T3, the state of
      proliferation of hepatocytes was estimated from the incorporation of 5'-bromo-2'
      deoxy-uridine (BrdU). The amphotropic retroviral receptor (Ram-1) expression of
      liver was evaluated at different time points after injecting HGF and T3 by means
      of Northern blotting using Ram-1 cDNA probe. In order to evaluate the role of
      hormone treatment on gene transfer, the liver was perfused exsanguineously with
      rMoMuLV 24 h after injection with hormones. RESULTS: Rats treated with a
      combination of HGF and T3 expressed BrdU and beta-galactosidase in 8.3% and 0.7%
      of hepatocytes, respectively. On the other hand, there was near absence of gene
      transfer in untreated rats perfused with rMoMuLV Twenty-four hours after the
      initial manipulation, abundant expression of Ram-1 mRNA was observed in rat
      hepatocytes treated with HGF plus T3. CONCLUSIONS: Stimulation of hepatocellular
      mitosis and upregulation of Ram-1 expression by HGF and T3 augment retrovirus
      mediated gene transfer into hepatocytes.

PMID- 10952236
TI  - Hepatic lipid accumulation, altered very low density lipoprotein formation and
      apolipoprotein E deposition in apolipoprotein E3-Leiden transgenic mice.
AB  - BACKGROUND/AIM: Apolipoprotein (apo) E-deficiency leads to hepatic steatosis and
      impaired Very Low Density Lipoprotein (VLDL)-triglyceride production rates in
      mice. A mutant apoE isoform, apoE3-Leiden, is associated with a dominantly
      inherited form of dysbetalipoproteinemia in humans. The aim of this study was to
      evaluate the effects of APOE*3-Leiden expression on hepatic lipid content, VLDL
      formation and liver morphology in mice. METHODS: Comparison of lipid parameters
      and liver morphology in mouse strains with different expression of the APOE*3
      Leiden transgene with and without co-expression of human APOCI. RESULTS: Hepatic
      triglyceride content was increased to maximally 233% of control values, depending
      on hepatic APOE*3-Leiden expression. Hepatic secretion of VLDL-associated
      triglycerides was impaired (-20%) in high-expressing transgenics, with a
      concomitant increase from 1.6 to 8.1 of the apoB48/ apoB100 ratio in newly-formed
      VLDL. Hepatocytes of the transgenic mice contained characteristic inclusions, up
      to 20 microm in diameter, in numbers dependent on APOE*3-Leiden expression and
      independent of APOCI expression. These inclusions contained material positively
      reacting with antihuman apoE antibodies. Immunogold-labeling confirmed the
      presence of apoE3-Leiden within these inclusions and also revealed the presence
      of the mutant protein on sinusoidal membranes, in multivesicular bodies and in
      peroxisomes, i.e., a distribution pattern similar to that of endogenous apoE in
      rodents. Nascent VLDL particles associated with the Golgi apparatus were also
      labeled. CONCLUSION: This study has demonstrated that introduction of human apoE3
      Leiden in mice, in addition to its reported effects on lipolysis and lipoprotein
      clearance, leads to hepatic deposition of the mutant apolipoprotein, development
      of fatty liver and to altered hepatic VLDL secretion. The latter findings are
      consistent with a role of apoE in the regulation of intrahepatic lipid
      metabolism.

PMID- 10952237
TI  - Early perturbations in keratin and actin gene expression and fibrillar
      organisation in griseofulvin-fed mouse liver.
AB  - BACKGROUND/AIMS: Long-term feeding of mice with a diet containing griseofulvin
      results in the formation of Mallory bodies, keratin K8 and K18 containing
      aggregates in hepatocytes. These bodies are biochemically and morphologically
      identical to the Mallory bodies that emerge in several human liver disorders. The
      aim of this study was to examine the contribution of K8 and K18 and actin to
      Mallory body formation. METHODS: Mice were fed griseofulvin over a period ranging
      from 1 day to 20 months. Hepatocyte morphology was monitored by
      immunocytochemistry, gene expression by Northern and run-off transcription
      assays, and protein level by Western blotting. RESULTS: Griseofulvin feeding
      induced a series of morphological alterations in hepatocytes that could be
      grouped into 3 phases: appearance of cholestasis during the first week (phase I),
      partial hepatocyte recovery at 3 months (phase II), and development of typical
      Mallory bodies after 3 to 5 months (phase III). All these cellular alterations
      were associated with perturbations in keratin and actin fibrillar status, coupled
      with increases in K8, K18 and actin mRNA steady-state level and, in K8 and K18
      protein content. The transcriptional activity of the genes was not affected.
      CONCLUSIONS: Perturbations in keratin and actin gene expression and fibrillar
      organisation constitute early events in the griseofulvin-induced pathological
      process that in the long-term leads to Mallory body formation. The higher keratin
      and actin mRNA levels reflect significant increases in mRNA stability taking
      place at the early phase of griseofulvin intoxication in hepatocytes.

PMID- 10952238
TI  - Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune
      hepatitis.
AB  - BACKGROUND/AIMS: Auto-immune hepatitis patients are divided into two well-defined
      subgroups on the basis of immunoserological markers, i.e. anti-actin cable and/or
      anti-nuclear antibodies for the auto-immune hepatitis type 1, anti-liver/kidney
      microsome type 1 and/or anti-liver cytosol type 1 for the autoimmune hepatitis
      type 2. Controversial antibodies to a soluble liver antigen have been proposed as
      a diagnostic marker for the putative auto-immune hepatitis type 3. The aim was to
      investigate the implication of anti-soluble liver antigen antibodies in the
      diagnosis of auto-immune hepatitis and their ability to define auto-immune
      hepatitis type 3. METHODS: Sera from 483 patients with hepatic and non-hepatic
      diseases, and 102 sera from blood donors were analyzed by an inhibition capture
      enzyme-linked immunosorbent assay. RESULTS: Anti-soluble liver antigen antibodies
      were found in 13 of the 106 (12%) auto-immune hepatitis type 1 patients and 10 of
      the 49 (20%) cryptogenic hepatitis patients tested. In contrast, they were not
      detected in auto-immune hepatitis type 2 (n=54), primary sclerosing cholangitis
      (n=37), primary biliary cirrhosis (n=52), hepatitis C virus infection (n=105),
      alcoholic hepatitis (n=25), various non-hepatic autoimmune disorders (n=55) and
      in healthy blood donors (n=102). The clinical and biological features of
      antisoluble liver antigen-seropositive patients were similar to those of auto
      immune hepatitis type 1 and did not distinguish a subgroup of auto-immune
      hepatitis. CONCLUSION: The data support the concept that antisoluble liver
      antigen-positive cryptogenic hepatitis is similar to auto-immune hepatitis type
      1. Anti-soluble liver antigen antibodies can be considered as an additional and
      specific auto-immune hepatitis type 1 diagnostic marker.

PMID- 10952239
TI  - Relationship between hepatic mitochondrial functions in vivo and in vitro in rats
      with carbon tetrachloride-induced liver cirrhosis.
AB  - BACKGROUND/AIMS: The metabolic capacity of liver mitochondria is impaired in rats
      with carbon tetrachloride (CCl4)-induced cirrhosis. These studies were performed
      to find out whether benzoate and/or palmitate are suitable substrates for
      assessing hepatic mitochondrial function in vivo. METHODS: In vivo metabolism of
      benzoate and 1-14C-palmitate was assessed by monitoring urinary excretion of
      hippurate and exhalation of 14CO2, respectively, in cirrhotic and control rats
      (n=8 for each group). Isolation of liver mitochondria, and in vitro benzoate and
      palmitate metabolism were performed by methods published previously. The hepatic
      content of mitochondria was assessed by stereological analysis of the volume of
      hepatocytes and by biochemical determination, using the activity of citrate
      synthase. RESULTS: Renal excretion of hippurate following i.p. administration of
      benzoate was reduced in cirrhotic rats (64+/-15 vs. 85+/-14% of administered dose
      over 24 h), and showed a linear correlation with hippurate formation by isolated
      mitochondria. The activities of benzoyl-CoA synthase and benzoyl-CoA:glycine N
      acyltransferase were reduced by approximately 60%, and the coenzyme A content by
      50% in hepatic mitochondria from cirrhotic rats, explaining impaired hippurate
      formation. Peak exhalation of 14CO2 after i.p. administration of 1-14C-palmitate
      was reduced by 44% and the area under the 14CO2 exhalation-time curve by 34% in
      cirrhotic rats. Peak 14CO2 exhalation revealed a linear correlation with
      oxidative metabolism of palmitoylcarnitine in isolated mitochondria. Both in vivo
      benzoate and palmitate metabolism showed a linear correlation with the volume
      fraction of hepatocytes. The mitochondrial protein content was reduced in
      cirrhotic rats per g liver and per liver but equal to control rats per volume of
      hepatocytes. CONCLUSIONS: In vivo metabolism of both palmitate and benzoate
      reflects hepatic mitochondrial function in rats with CCl4-induced cirrhosis.
      Hepatic mitochondrial function is impaired in rats with CCl4-induced cirrhosis
      due to both reduced mitochondrial volume per liver and impaired metabolism of the
      remaining mitochondria. In contrast to rats with secondary biliary cirrhosis,
      rats with CCl4-induced cirrhosis showed no hepatic mitochondrial proliferation to
      counteract reduced mitochondrial function.

PMID- 10952240
TI  - Gene expression of interstitial collagenase in both progressive and recovery
      phase of rat liver fibrosis induced by carbon tetrachloride.
AB  - BACKGROUND/AIMS: Liver fibrosis is a dynamic state between matrix production and
      degradation. Since our report in 1974, many studies have examined collagenase and
      liver fibrosis, but not the identification of cells responsible for collagenase
      production in vivo. The aim of this study was to investigate the gene expression
      of interstitial collagenase in the progressive and recovery phases of
      experimental rat liver fibrosis by in situ hybridization. METHODS: We examined
      the gene expression of interstitial collagenase (MMP-13) in the progressive and
      recovery phase of experimental rat liver fibrosis induced by chronic CCl4
      intoxication by reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization. In order to identify the cells expressing MMP-13 mRNA by in
      situ hybridization, immunohistochemistry was performed using serial sections.
      RESULTS: In normal rat liver, a faint band for MMP-13 mRNA was observed by RT
      PCR, but not by in situ hybridization. The livers of rats treated with CCl4 for 4
      weeks showed fatty metamorphosis but no definite fibrosis. Positive signals for
      MMP-13 mRNA were observed in scattered mesenchymal cells, within lobules which
      seem to be stellate cells from immunohistochemical staining. Once the fibrosis
      became prominent, the faint band for MMP-13 mRNA was detected only by RT-PCR and
      very few signals, if any, by in situ hybridization. On the other hand, in the
      recovery phase of liver fibrosis, gene expression of MMP-13 was markedly
      enhanced. Strong positive cells by in situ hybridization were observed mainly at
      the interface between the resolving fibrous septa and the parenchyma. Overlapping
      both images of in situ hybridization and immunohistochemical staining with the
      help of a computer revealed that some positive cells, but not all cells, were
      stellate cells stained with a-smooth muscle actin antibody. CONCLUSIONS: MMP-13
      participates in the degradation of newly-formed matrix in the recovery from rat
      liver fibrosis more than in the remodeling of extracellular matrix for the
      formation of fibrosis. Hepatic stellate cells play a crucial role in MMP-13
      production in the recovery from fibrosis, though not all stellate cells were
      positive for MMP-13 mRNA. Further investigation into gene expression of MMP-13 in
      recovery will lead to new strategies for the treatment of liver cirrhosis.

PMID- 10952241
TI  - Atrial natriuretic peptide reduces expression of TNF-alpha mRNA during
      reperfusion of the rat liver upon decreased activation of NF-kappaB and AP-1.
AB  - BACKGROUND/AIMS: The cardiovascular hormone Atrial Natriuretic Peptide (ANP)
      attenuates activation of the pro-inflammatory transcription factor NF-kappaB in
      macrophages. ANP was also shown to protect from ischemia-reperfusion injury of
      the rat liver. This study aimed to investigate the effects of this
      immunomodulatory hormone and its second messenger cGMP on the activation of the
      two redox-sensitive transcription factors AP-1 and NF-kappaB and the expression
      of corresponding pro-inflammatory target genes during ischemia and reperfusion of
      the liver. The identification of the mechanisms underlying the protection by ANP
      should reveal new aspects concerning the pathomechanisms of ischemia/reperfusion
      injury. METHODS: Rat livers were perfused with and without ANP or 8-Br-cGMP
      preceding 24 h of cold storage in University of Wisconsin solution. During
      reperfusion NF-kappaB and AP-1 DNA binding activities were determined in freeze
      clamped liver samples by electrophoretic mobility shift assay. Protein levels of
      p50, p65, and of IkappaB were determined by Western blot. mRNA coding for
      inducible nitric oxide synthase, cyclooxygenase-2, and TNF-alpha was determined
      by RT-PCR and Northern blot. RESULTS: After 45 min of reperfusion DNA binding
      activities of NF-kappaB were increased, whereas in ANP pre-treated livers this
      effect was markedly reduced. AP-1, another important redox-sensitive
      transcription factor, was activated and in the course of reperfusion the subunit
      composition of AP-1 changed as assessed by supershift assays. ANP markedly
      reduced binding activities of both forms of AP-1. 8-Br-cGMP mimicked the effects
      of ANP on NF-kappaB and AP-1. Neither inducible nitric oxide synthase nor
      cyclooxygenase-2 mRNA could be detected. In contrast, a profound expression of
      transcripts coding for TNF-alpha was detected in the course of reperfusion and
      ANP markedly reduced TNF-alpha mRNA expression. CONCLUSION: ANP seems to mediate
      its protective effect during ischemia and reperfusion by reducing the activation
      of NF-kappaB and AP-1 via cGMP. The reduced binding activity of these redox
      sensitive transcription factors was accompanied by a diminished mRNA expression
      of TNF-alpha, a cytokine known to be involved in cellular damage in ischemia
      reperfusion injury.

PMID- 10952242
TI  - Prognostic significance of glutamine synthetase expression in unifocal advanced
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Glutamine synthetase (GS) catalyzes the synthesis of glutamine,
      a major energy source of cells, and is upregulated in a subset of human
      hepatocellular carcinomas (HCCs). GS expression may be related to tumor
      recurrence, since GS-expressing tumors have a growth advantage in that they are
      independent of the extracellular glutamine supply. However, there are no studies
      concerning the prognostic value of GS expression in patients with HCC. METHODS:
      Seventy-three patients with a single advanced HCC nodule who underwent curative
      hepatectomy were included in the study. GS expression in the HCC nodules was
      analyzed immunohistochemically and was compared with clinicopathologic features
      and the behavior of the tumors. Survival curves were assessed according to the
      Kaplan-Meier product-limit method and multivariate analysis based on the Cox
      regression model was performed. RESULTS: GS expression was strong in 26 cases
      (35.6%, high-GS group) and weak or absent in 47 cases (64.4%, low-GS group).
      Univariate analysis showed that the high-GS group had a significantly shorter
      disease-free survival time than the low-GS group (p=0.042). Multivariate analysis
      revealed that GS expression (p=0.021), as well as Child's classification
      (p=0.005) and portal invasion (p=0.039), was a significant and independent
      prognostic parameter that affected tumor recurrence. CONCLUSION: The results of
      this study indicate that GS expression may enhance the metastatic potential in
      HCC, and GS immunostaining may be helpful in identifying HCC patients at high
      risk for disease recurrence.

PMID- 10952243
TI  - P53 but not p16INK4a induces growth arrest in retinoblastoma-deficient
      hepatocellular carcinoma cells.
AB  - BACKGROUND/AIM: Both p16INK4a and p53 proteins are negative regulators of the
      cell cycle. In human hepatocellular carcinomas (HCC), the loss of function of
      p53, retinoblastoma (pRb) and pl6INK4a genes by different mechanisms has been
      largely documented, but their hepatocellular effects are poorly known. We
      compared the growth-inhibitory effects of p16INK4a and p53 proteins in Hep3B cell
      line-derived clones. METHODS: Cells were transfected with inducible p16INK4a and
      p53 expression vectors, and stable clones were analyzed for transgene expression
      by Western blotting and immunoperoxidase staining. Effects on cell growth were
      analyzed by in vitro growth assay, thymidine incorporation and flow cytometry.
      Biochemical effects of p53 were tested by Northern blotting of p21Cip1
      transcripts and by Western blotting of p21Cip1, mdm-2, bax, cyclin-dependent
      kinase 2 and cyclin E proteins. The pRb protein was studied by Western blotting
      and immunoprecipitation assays. RESULTS: The induction of p16INK4a protein
      expression did not affect in vitro growth of cells. In contrast, p53 protein in
      its wild-type conformation provoked a growth arrest accompanied by
      transactivation of p21Cip1 gene and accumulation of p21Cip1, bax and mdm-2
      proteins. p53-induced growth arrest was due to a cell cycle arrest at the G1/S
      transition, probably mediated by p21Cip1 protein, which inhibits cyclin-dependent
      kinase 2/cyclin E complexes. CONCLUSIONS: The lack of detectable pRb protein and
      resistance of cells to p16TNK4a strongly suggest that p53 is able to arrest the
      growth of HCC cells by a mechanism independent of "p53-retinoblastoma pathway".
      These findings are applicable to HCC with abberrations of both p53 and pRb genes,
      and may not represent the universal effects of p53 in hepatic cells.

PMID- 10952244
TI  - Differential association of p21Cip1 and p27Kip1 with cyclin E-CDK2 during rat
      liver regeneration.
AB  - BACKGROUND/AIMS: The cell cycle inhibitors p21Cip1 and p27Kip1 regulate liver
      regeneration by modulating the activity of cyclin-dependent kinases (CDKs).
      However, the specific role of these inhibitors in the regulation of CDK2 activity
      during liver regeneration remains unknown. The aim of this study was to examine
      the association of p21Cip1 and p27Kip1 with cyclin E-CDK2 and cyclin A-CDK2
      complexes during rat liver regeneration and to correlate the association of both
      inhibitors with CDK2 activity. METHODS: The association of p21Cip1 or p27Kip1
      with cyclin E-CDK2 or cyclin A-CDK2 and the activities of these complexes were
      analyzed by immunoprecipitation of rat liver homogenates obtained at different
      times after a partial hepatectomy (PH), followed by Western blotting or kinase
      assays. RESULTS: High amounts of p27Kip1 bound to cyclin E-CDK2 were observed
      during the first 13 h after PH, when CDK2 activity was very low. At 24 h, when
      CDK2 activity was maximal, the amount of bound-p27Kip1 decreased strongly. The
      amount of p21Cip1 bound to these complexes was low during the first 13 h but
      subsequently increased. No cyclin A-CDK2 complexes were found during the first 13
      h after PH. At 24 h, complexes containing low levels of both inhibitors were
      detected and at 28 h, a significant increase in p21Cip1 and p27Kip1 associated
      with cyclin A-CDK2 was observed. CONCLUSIONS: p27Kip1 acts as a brake on cyclin E
      CDK2 activity during the first 13 h after a PH. Both p21Cip1 and p27Kip1 down
      regulate cyclin A-CDK2 activity at 28 h after PH, after its maximal activation.

PMID- 10952245
TI  - Epidermal growth factor is decreased in liver of rats with biliary cirrhosis but
      does not act as paracrine growth factor immediately after hepatectomy.
AB  - BACKGROUND/AIMS: Epidermal growth factor, a potent mitogen for hepatocytes and
      cholangiocytes, is thought to act as an immediate-early gene after partial
      hepatectomy. Since regeneration is impaired in cirrhosis, we explored the
      expression of epidermal growth factor in cirrhotic rat liver immediately after
      partial hepatectomy. METHODS: Cirrhosis was induced by bile duct ligation (n=21);
      sham-operated animals served as controls (n=21). Twenty-five days after initial
      surgery animals were subjected to 70% partial hepatectomy or sham operation; the
      liver was sampled before surgery and 20, 40 and 90 min thereafter. Epidermal
      growth factor mRNA levels were assessed by quantitative reverse transcription
      polymerase chain reaction. Protein expression was estimated by
      immunohistochemistry using a polyclonal antibody against epidermal growth factor.
      RESULTS: Before hepatectomy, epidermal growth factor mRNA averaged 70.3+/-39.9
      pg/microg of total RNA in controls; this was markedly decreased to 21.9+/-12.7
      pg/microg RNA in bile duct ligation (p<0.01). Epidermal growth factor mRNA did
      not increase after partial hepatectomy in either group, with the exception of
      sham-operated controls. Immunohistochemistry revealed that partial hepatectomy
      had no effect on epidermal growth factor expression. Hepatocytes showed uniformly
      cytosolic epidermal growth factor in controls, while in bile duct ligation
      immunostaining was faint or absent. Cholangiocytes exhibited a strong cytosolic
      staining in all experimental groups. CONCLUSIONS: The present study shows that
      epidermal growth factor is reduced in the cirrhotic liver. This could contribute
      to the loss of parenchymal liver tissue observed in cirrhosis. The lack of up
      regulation after PH sheds doubt on the role of epidermal growth factor as an
      immediate-early gene in hepatic regeneration. Further, we demonstrate that
      epidermal growth factor accumulates in cholangiocytes. This observation is strong
      evidence for involvement of the mitogen epidermal growth factor in the
      proliferation of bile ducts during cirrhogenesis.

PMID- 10952246
TI  - Pathomorphologic study on the mechanism of fatty change in small hepatocellular
      carcinoma of humans.
AB  - BACKGROUND/AIMS: Fatty change is frequently observed in small hepatocellular
      carcinoma (HCC) of the early stage. However, the mechanism of fatty change and
      its pathomorphological features in small HCC are not yet fully understood. These
      issues are addressed here. METHODS: Histological examinations were conducted on
      260 HCC nodules (< or =3 cm in diameter) which were surgically obtained from 249
      patients. According to the distribution pattern, fatty changes were classified
      into two types: 'diffuse type' when the change was found throughout the cancerous
      nodule; and 'focal type' when the change was localized in part of the nodule. To
      study the pathogenesis of fatty change in HCC in relation to angioarchitecture,
      the number of arterial tumor vessels and intratumoral portal tracts in 104 of the
      260 nodules was counted. RESULTS: Fatty change was found in 51 of the 260 nodules
      (19.6%), the frequency was highest (36.4%) in the nodules whose diameter was 1.1
      to approximately 1.5 cm, and the frequency decreased with the increase in tumor
      diameter. Small well-differentiated HCCs were often associated with a diffuse
      type fatty change. With the increase in tumor diameter, moderately differentiated
      cancerous tissues without associated fatty change appeared, and the focal type
      was found more frequently. According to the angioarchitecture, in HCCs < or =1.5
      cm, the number of intratumoral arteries was significantly smaller in HCCs with
      fatty change (p<0.05), though the number of intratumoral portal tracts was not
      significantly different compared with HCCs without fatty change. CONCLUSION:
      These findings suggest that fatty change of small HCC is closely related to the
      tumor size, the histological grade and insufficient development of the arterial
      tumor vessels.

PMID- 10952247
TI  - Establishment and characterization of a spontaneously immortalized myofibroblast
      cell line derived from a human liver angiosarcoma.
AB  - BACKGROUND/AIM: Fibrosis and/or cirrhosis are present in the precursor stages of
      most liver cancers. However, little is known about the reciprocal interactions of
      fibroblasts, mainly responsible for fibrosis, and the other liver cells. We
      report here the isolation of a new liver myofibroblast cell line from a human
      liver angiosarcoma and its characterization. METHODS: The cells were isolated by
      the explant technique and characterization was performed, on one hand, using
      immunohistochemical and ultrastructural analysis and, in the other hand, by
      determining their karyotype, ras and p53 status and their tumorigenic properties.
      RESULTS: To date, the cells have undergone approximately 170 population doublings
      and are still proliferating. Immunohistochemically, they were negative for
      desmin, smooth muscle myosin, cytokeratin 19 and von Willebrand factor, positive
      for vimentin and alpha-smooth muscle actin, with an important deposition of
      fibronectin around the cells. Ultrastructure showed particularly cytoplasmic
      microfilament bundles. Their chromosome number ranged from 38 to 168 with a
      bimodal population, near diploid and hypotetraploid. No mutations were found in
      codons 12, 13 or 61 of Ha-, Ki- and N-ras genes but a homozygous missense
      mutation in codon 179 (CAT-->CTT) was detected in the p53 gene. They were unable
      to form foci in soft agar or tumors in nude mice. CONCLUSIONS: Taken together,
      these results show that these cells, called BM 2.2.1, exhibited typical
      myofibroblast-like features. Although they contained a karyotype suggestive of
      tumoral cells and a homozygous mutated p53 gene, they were not tumorigenic. The
      nature of these cells and the abnormalities of the p53 gene and the karyotype,
      suggest that: i) they were a component of the tumor stroma, and ii) they could
      have been involved in angiosarcoma development. Thus, this cell line may be
      valuable for the study of cellular interactions in liver carcinogenesis.

PMID- 10952248
TI  - Lamivudine treatment in patients with severely decompensated cirrhosis due to
      replicating hepatitis B infection.
AB  - BACKGROUND/AIMS: Lamivudine is highly effective in suppressing hepatitis B viral
      replication and hepatic necroinflammatory activity. The potential for recovery of
      hepatic decompensation in patients with chronic hepatitis B infection treated
      with lamivudine has not been established. The aim of this study was to evaluate
      the effectiveness of lamivudine treatment in severely decompensated cirrhosis due
      to chronic hepatitis B. METHODS: Thirteen consecutive patients with chronic
      hepatitis B infection, Child's-Pugh-Turcotte (CPT) score of > or =10 (median
      score=11) and detectable circulating hepatitis B DNA (range 15 to 9634 pg/ml)
      were included and treated with lamivudine 150 mg once daily. Hepatitis B envelope
      antigen (HBeAg) was positive in 9 of 13 patients pre-treatment. RESULTS: Two
      patients underwent liver transplantation at 4 and 6 weeks after starting
      lamivudine treatment. The remaining 11 patients were followed for a mean of 17.5
      months without liver transplantation (range 3 to 39 months). Significant
      improvement of liver function, defined as a decrease in CPT score of > or =3, was
      observed in 9 of 13 patients (69%). In five patients, CPT score improved to <7
      and they were placed on the inactive status (UNOS status 7) for liver
      transplantation. Hepatitis B DNA remained negative in all except one patient who
      developed breakthrough viral replication 12 months after starting lamivudine
      treatment, while maintaining stable liver function. Three of seven HBeAg-positive
      patients who did not undergo liver transplantation lost HBeAg during follow-up,
      but none had sustained seroconversion to hepatitis B e antibody. CONCLUSION:
      Lamivudine appears highly effective in reversing severe hepatic decompensation
      due to replicating hepatitis B infection.

PMID- 10952249
TI  - Beneficial effects of lamivudine in hepatitis B virus-related decompensated
      cirrhosis.
AB  - BACKGROUND/AIMS: HBV-related chronic liver disease patients often present with
      hepatic decompensation and are not eligible for interferon therapy. Whether long
      term lamivudine is effective in these patients was prospectively evaluated.
      METHODS: Eighteen patients with HBV-related decompensated cirrhosis, all with
      quantitative DNA +ve and 10 HBeAg +ve, were given lamivudine 150 mg/d. RESULTS:
      Each patient received at least 9 months (mean 17.9) of lamivudine. Three HBeAg+ve
      patients (30%) seroconverted to anti-HBe and one lost HBsAg during the follow-up.
      An improvement from baseline in the aspartate aminotransferase (130 vs. 72 IU/l,
      p<0.04); alanine aminotransferase (111 vs. 58 IU/l, p<0.01) and Child-Pugh score
      (8.3 vs 6.7, p<0.013) was seen. Lamivudine had no significant side-effects. HBV
      DNA became undetectable in all patients by 8 weeks of therapy. In three (17%)
      patients, HBV DNA again became positive at 9, 9 and 27 months. YMDD mutant was,
      however, detected in only one (6%). A significant reduction was noted in the
      morbidity and hospitalizations for complications of liver disease before and
      after starting lamivudine (1.5+/-0.7 vs. 0.6+/-0.7, p<0.002). CONCLUSIONS: In
      decompensated HBV-related cirrhosis, lamivudine: i) is effective in suppressing
      HBV DNA and seroconversion to anti-HBe (30%), ii) can achieve significant
      improvement in clinical and biochemical status of liver functions.

PMID- 10952250
TI  - Different turnover rate of hepatitis C virus clearance by different treatment
      regimen using interferon-beta.
AB  - BACKGROUND/AIM: Since patients with high viral load and HCV subtype 1b are known
      to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA
      after initiation of interferon therapy were examined in the present study with
      respect to two different administration regimens, once vs. twice a day. METHODS:
      Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with
      >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different
      IFN administration regimens (6 million units of IFN once a day or 3 million units
      of IFN twice a day), and the serum HCV RNA level was serially measured. RESULTS:
      Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall,
      followed by a slower clearance phase. Fitting the data to a model for HCV decay
      proposed by Neumann et al. showed that the treatment efficacy was significantly
      higher with twice daily administration. Negativity for HCV RNA measured by
      Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at
      1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively,
      with once-a-day administration. However, a significant reduction of platelet
      count and albumin level, a marked increase in serum aspartate
      aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity
      (proteinuria) were found in patients receiving IFN twice a day in comparison with
      those receiving it once a day. CONCLUSION: The twice-a-day administration of IFN
      accelerated the clearance of HCV RNA from serum, leading to a more efficient
      virological response for patients with chronic hepatitis C, but with a high rate
      of renal toxicity.

PMID- 10952251
TI  - It's swell to have ATP in the liver.

PMID- 10952252
TI  - Antibodies to soluble liver antigen: specific marker of autoimmune hepatitis.

PMID- 10952253
TI  - Lamivudine treatment in patients with decompensated hepatitis B cirrhosis: for
      whom and when?

PMID- 10952254
TI  - Regulation and deregulation of cholangiocyte proliferation.

PMID- 10952255
TI  - Angiosarcoma of the liver presenting with esophageal bleeding and arterio-portal
      shunts.

PMID- 10952256
TI  - Infectious agents and primary biliary cirrhosis.

PMID- 10952257
TI  - How long to treat chronic hepatitis B virus infection with lamivudine?

PMID- 10952258
TI  - Detection of congenital malaria by polymerase-chain-reaction methodology in Dar
      es Salaam, Tanzania.
AB  - The examination of congenital malaria was performed by Giemsa staining and
      polymerase-chain-reaction (PCR) methodology. We randomly selected 298 neonates
      who had been admitted to Muhimbili Medical Center (MMC) at Dar es Salaam,
      Tanzania. One baby among all the enrolled neonates was recognized as having a
      congenital malaria infection, which gave a prevalence of 0.33%. The present
      result was 5-fold the clinically recognized prevalence of congenital infection
      with malaria in the ward. The PCR method identified two cases, one of which was
      negative as determined by the Giemsa-staining method. Therefore, the PCR method
      was useful for the detection of scant amounts of malarial parasites in numerous
      blood samples. The screening of malaria by a sensitive PCR method contributes to
      reduce the mortality of asymptotic neonates in particular.

PMID- 10952259
TI  - "Spring rise" of whaleworm (Anisakis simplex; Nematoda, Ascaridoidea) third-stage
      larvae in some fish species from Norwegian waters.
AB  - The seasonal variation in the infection of saithe (Pollachius virens), cod (Gadus
      morhua), and redfish (Sebastes marinus) from a coastal area of central Norway
      with Anisakis simplex third-stage larvae (L3) was studied over a period of 1
      year. In all three host species there was an increase in the abundance of the
      parasite in spring, with a peak appearing in March and April. Cod displayed the
      most distinct seasonal variation, showing a clear abundance peak in April. The
      abundance peak in April for redfish was not as pronounced. In saithe the
      abundance over the seasons was less prominent, with a maximum appearing in March
      and another increase in abundance occurring during July. It is apparent that the
      causes behind the pattern of infection observed in this study are complex.
      However, possible explanatory mechanisms are discussed. Arguments are propounded
      to suggest that the increased supply of parasite eggs from northward-migrating
      whales in addition to the general spring bloom of plankton constitute the most
      important factors governing the phenomenon of "spring rise" in A. simplex L3 in
      the study area.

PMID- 10952260
TI  - Effect of the antitubulin drug oryzalin on the encystation of Entamoeba invadens.
AB  - We have recently demonstrated that the antimicrotubule drug oryzalin inhibits the
      growth of Entamoeba invadens as well as E. histolytica, the former being more
      resistant to the drug than the latter, and that effective doses of oryzalin are
      higher for Entamoeba than for the other parasitic protozoa examined thus far. The
      aim of the present study was to examine the effect of oryzalin on the encystation
      of E. invadens using an axenic encystation system in vitro. Oryzalin inhibited
      the encystation of E. invadens strain IP-1 in a dose-dependent manner. The
      addition of oryzalin after the induction of encystation was also inhibitory for
      encystation and cyst maturation. Trophozoites incubated for 1 day in encystation
      medium with oryzalin did not encyst after removal of the drug. Although
      trophozoites grown in the presence of 300 microM oryzalin for 2 days did not
      encyst after their transfer to encystation medium containing the same
      concentration of drug, a number of trophozoites survived for at least 3 days. In
      contrast, trophozoites grown in the absence of oryzalin neither survived nor
      encysted after their transfer to encystation medium supplemented with the drug,
      which suggests that pretreatment of trophozoites with oryzalin contributes to
      their continued survival as trophozoites, i.e., without their transforming into
      cysts, in encystation medium. Trophozoites grown with oryzalin did encyst after
      their transfer to encystation medium without the drug. Accumulation of
      trophozoites in the mitotic phase was observed after culture with oryzalin. When
      cysts prepared at day 1 of encystation, most of which were mononucleate, were
      reincubated in the presence of oryzalin for an additional 2 days, inhibition of
      their maturation was observed. Thus, oryzalin is a potent mitotic-phase inhibitor
      of E. invadens and may become a useful tool for studies on the relationship
      between the cell cycle and encystation of this parasite.

PMID- 10952261
TI  - Effects of bile on the in vitro hatching, exsheathment, and migration of Ascaris
      suum larvae.
AB  - This study reports on the in vitro egg hatching, exsheathment, migratory
      activity, and sensitivity to anthelmintics of Ascaris suum larvae in cultures
      with or without bovine bile. Three methods for egg hatching and/or incubation
      were used: an object-glass method, a glass-bead method, and an incubation method.
      An agar migration assay (AMA) was developed to test the migratory activity of
      Ascaris larvae following hatching. Bile appeared to be an important stimulatory
      factor for both egg hatching and larval mobility in the incubation method.
      Incubation in low concentrations of bile (2%, 5%, or 10%) stimulated both egg
      hatching and larval migration, whereas concentrations of at least 20% impaired
      egg hatching and larval migration. Furthermore, 5% bile seemed to promote
      exsheathment of A. suum larvae.

PMID- 10952264
TI  - Drug-abbreviated infections of Trichostrongylus colubriformis and development of
      immunity in jirds (Meriones unguiculatus).
AB  - The objective of this study was to examine the development and the duration of
      immunity achieved with drug-abbreviated infections of Trichostrongylus
      colubriformis in jirds (Meriones unguiculatus). Jirds were primarily infected
      either by trickle infection with 6 x 100 infective larvae (L3) of T.
      colubriformis at 3-day intervals or by a single infection with 600 L3. On day 35
      post-infection, one batch of jirds from each group was autopsied; the others were
      treated with oxfendazole at a dose of 5 mg/kg and were challenged with 1,000 L3
      on either day 7 or day 42 post-treatment. All jirds were autopsied at 17 days
      post-challenge. Trickle infection resulted in lower levels of egg production
      during the primary infection period. The systemic IgM and IgG antibody response
      was significantly stronger in trickle- and single-infected groups as compared
      with the negative control group (P < 0.01-P < 0.05). Significantly higher levels
      of intestinal IgA were demonstrated in trickle- and single-infected groups than
      in the negative control group (P < 0.01). Numbers of mucosal mast cells increased
      following infection, but this was not dependent on the type of immunisation.
      After challenge the extent of worm reduction was greater in trickle-infected than
      in single-infected subgroups. The IgM and IgG response was significantly stronger
      in challenged subgroups as compared with negative control subgroups (P < 0.01).
      However, the IgG response was weaker in control challenged subgroups than in
      challenged subgroups (P < 0.01). There was a negative correlation between the IgG
      response and the worm burden after the second challenge (r = -0.73). The acquired
      immunity to T. colubriformis infection in jirds developed within 5 weeks of
      primary infection. The level of immunity was higher after trickle infection than
      after single infection. Furthermore, the immunity persisted for at least 6 weeks
      after oxfendazole treatment in the absence of a worm burden and larval intake,
      which is very similar to the situation in domestic ruminant hosts.

PMID- 10952263
TI  - Genotypic status of Babesia microti within the piroplasms.
AB  - For resolution of the controversial taxonomic status of Babesia microti in
      relation to other Babesia and Theileria spp. a phylogenetic analysis of an
      American and a German B. microti strain was performed on the basis of sequences
      of the small-subunit rRNA gene (rDNA) using distance-matrix, maximum-parsimony,
      and maximum-likelihood algorithms. Both B. microti isolates clearly separated
      from a group containing other Babesia spp. as well as from a second group
      consisting of Theileria spp. Interestingly, the B. microti isolates clustered in
      a monophyletic group together with other piroplasm species of unclear taxonomic
      status, B. rodhaini, and a recently described small canine piroplasm species.
      These results support the existence of a third taxonomic entity of equal rank
      besides the Babesiidae and Theileriidae.

PMID- 10952262
TI  - Species specificity of a monoclonal antibody produced to Naegleria fowleri and
      partial characterization of its antigenic determinant.
AB  - Monoclonal antibody (Mab) 5D12 against Naegleria fowleri was analyzed for species
      specificity. Mab 5D12 reacted with a ubiquitous epitope present on the membrane
      of N. fowleri but not with soluble antigens. The Mab did not react with N.
      lovaniensis, N. gruberi, N. australiensis, or Acanthamoeba castellanii. The
      decreased reactivity of Mab 5D12 with N. fowleri observed after periodate
      oxidation, after digestion of carbohydrate moieties by three glycosidases, or
      after treatment of amebas with tunicamycin strongly suggests that the antigenic
      determinant has a polysaccharide component. Inhibition of the reactivity of Mab
      5D12 by soluble saccharides supports the idea that N-acetyl or amino groups may
      play an important role in the recognition of the carbohydrate component of the
      epitope by the Mab. The specificity of Mab 5D12 makes this an ideal reagent for
      the identification of N. fowleri in environmental samples or in clinical
      specimens.

PMID- 10952265
TI  - Prevalence and intensity of the blood parasite Hemolivia mariae in a field
      population of the skink Tiliqua rugosa.
AB  - The impacts of virulent parasites on humans or domestic animals are well
      documented. Less is known of the impact of parasites in natural host-parasite
      associations. A population of the Australian sleepy lizard Tiliqua rugosa is
      infected with the blood microparasite Hemolivia mariae, which is transmitted by
      the ectoparasitic tick Amblyomma limbatum. In most infected lizards a very small
      proportion, usually < 1%, of red blood cells are infected. A study of the
      prevalence of the microparasite in the field population found no difference
      either over 5 years of study or among times within a lizard activity season.
      Juvenile and sub-adult lizards and larger adults were less frequently infected
      with H. mariae than were other adults. In sub-adults this was related to a lower
      level of tick infestation. In adults, male and female lizards were equally
      frequently infected with H. mariae, but the presence or absence of ticks was not
      predictive of infection. The lizards' body condition was measured as the residual
      of the regression of log snout-vent length against log body mass. In female
      lizards the body condition was not affected by infection. In males the body
      condition declined over the sampling period each year, probably as a result of
      mate attendance. The body condition was poorer in male lizards with H. mariae
      infection than in uninfected males. Possible explanations for the associations of
      microparasites and host lizards are discussed.

PMID- 10952266
TI  - Arsenite-resistant Leishmania donovani promastigotes express an enhanced membrane
      P-type adenosine triphosphatase activity that is sensitive to verapamil
      treatment.
AB  - An arsenite-resistant strain of Leishmania donovani was generated in vitro by
      sequential exposure to higher concentrations of sodium m-arsenite. The resistant
      strain displayed a low level of cross-resistance to structurally unrelated drugs
      such as doxorubicin and pentamidine. This cross-resistance was sensitive to the
      calcium-channel blocker verapamil. The membrane-associated P-type adenosine
      triphosphatase (ATPase) activity detected in crude membrane fractions of the
      resistant strain was 3-fold that found in the wild-type parasites. The enhanced
      ATPase activity was unaffected by the presence of verapamil in the reaction
      mixture. However, when cells were grown in the presence of verapamil the membrane
      associated ATPase activity of the resistant strain showed significant inhibition.

PMID- 10952267
TI  - Antimalarial activity of new gossypol derivatives.
AB  - Gossypol, a disesquiterpene extracted from cotton seeds, is known to inhibit
      strongly the Plasmodium falciparum lactate dehydrogenase, but its high toxicity
      has stopped any antimalarial drug development. A series of Schiffs bases was
      synthesized from gossypol by modification of the aldehyde groups responsible for
      its toxicity. A total of 13 compounds showing low cytotoxicity were then selected
      and were compared with gossypol for activity against 2 chloroquine-resistant
      strains of P. falciparum (PFB, FCB1). These in vitro activities were evaluated
      using an isotope-based drug-susceptibility semiautomated microdilution test
      followed by determination of IC50 values (50% inhibitory concentration). In all,
      12 of the 13 compounds tested were active; 3 of them displayed antimalarial
      activity comparable with that of gossypol itself.

PMID- 10952269
TI  - Assessing sequence variation in the internal transcribed spacers of ribosomal DNA
      within and among members of the Contracaecum osculatum complex (Nematoda:
      Ascaridoidea: Anisakidae).
AB  - The anisakid nematodes of seals from different geographical origins, previously
      identified as Contracaecum osculatum A, C. osculatum B, C. osculatum C, C.
      osculatum D, C. osculatulm E and C. osculatum baicalensis by multilocus enzyme
      electrophoresis, were characterised using a DNA approach. The first and second
      internal transcribed spacers (ITS-1, ITS-2) of ribosomal DNA (rDNA) were
      individually amplified by polymerase chain reaction (PCR) and analysed by single
      strand conformation polymorphism (SSCP) and sequencing. SSCP analyses allowed the
      unequivocal differentiation of all taxa except C. osculatum D from C. osculatum
      E. While C. osculatum D and C. osculatum E had identical ITS sequences, each of
      the other four taxa had distinct sequences, with interspecific differences
      ranging from 0.3% to 2.3%. C. osculatum C was genetically the most distinct taxon
      with respect to all other members of the species complex.

PMID- 10952268
TI  - Taxonomic position of the human intestinal protozoan parasite Isospora belli as
      based on ribosomal RNA sequences.
AB  - The taxonomic positions of Isospora belli and other members of the genus Isospora
      are controversial. We determined the small-subunit ribosomal RNA of I. belli and
      used this sequence in combination with other coccidian RNA sequences for analysis
      of the taxonomic position of I. belli. The phylogenetic trees we obtained provide
      molecular evidence for three clades within a monophyletic group that represents
      the suborder Eimeriina. The clade containing I. belli consists of tissue-cyst
      forming coccidia (Toxoplasma and Neospora) and members of the genus Isospora (I.
      ohioensis, I. suis, I. belli). The second clade, representing a sister clade of
      that containing the Isospora species, contains members of the genus Sarcocystis.
      The third one consists of members of the family Eimeriidae, including Eimeria and
      Cyclospora species. This shows that although I. belli as well as other members of
      the genus Isospora belong to the suborder Eimeriina, the family to which they
      belong is not Eimeriidae but rather Sarcocystidae. We suggest that the genus
      Isospora should be removed from the family Eimeriidae and placed into the family
      Sarcocystidae within the suborder Eimeriina.

PMID- 10952270
TI  - Partial characterization of serine proteinases secreted by adult Trichinella
      spiralis.
AB  - Serine proteinases secreted by adult Trichinella spiralis were isolated from
      excretory/secretory products (ES) of in-vitro-cultured parasites by affinity
      chromatography with p-benzamidine-celite. The purified enzymes had molecular
      weights of approximately 18, 40, and 50 kDa and displayed enzyme activity against
      a range of low-molecular-weight substrates, gelatin, and azocasein. The
      antigenicity of these parasite proteinases was demonstrated by the inhibition of
      enzymatic activity with IgG purified from infected hosts. The inactivation of
      major secreted proteinases of adult T. spiralis by immune antibody could
      presumably contribute to impairment of the survival of the parasite in sensitized
      hosts.

PMID- 10952271
TI  - Cadmium accumulation in Moniliformis moniliformis (Acanthocephala) from
      experimentally infected rats.
AB  - The accumulation of cadmium in Moniliformis moniliformis parasitizing
      experimentally infected rats that had been orally exposed to cadmium was
      investigated in this study. Cadmium accumulation in the helminth and in different
      tissues of the host was determined using electrothermal atomic absorption
      spectrometry (AAS) after a 3-week period of exposure. The mean cadmium
      concentration measured in M. moniliformis was 5.8 microg g(-1) wet weight, which
      was 20, 23, and 119 times higher than that determined in the kidney, liver, and
      intestine of the host, respectively. Although female worms accumulated higher
      amounts of cadmium than did males, no tendency emerged between the cadmium
      concentration and the weight of individual acanthocephalans. This study reveals
      that cadmium accumulation also occurs in archiacanthocephalans, but to a lesser
      degree than in palaeacanthocephalans parasitizing fish. Due to its cadmium
      accumulation capacity, M. moniliformis might be used as a highly sensitive free
      living bioindicator in terrestrial and urban ecosystems.

PMID- 10952273
TI  - Whose scans are they, anyway?

PMID- 10952272
TI  - Plasmodium falciparum: a comparative analysis of the genetic diversity in malaria
      mesoendemic areas of Brazil and Madagascar.
AB  - For a better definition of the polymorphic features of Plasmodium falciparum
      parasite populations, the polymerase chain reaction (PCR) typing technique was
      used to investigate the genetic diversity and complexity of parasites harbored by
      acute P. falciparum carriers from three yet unexplored malaria-mesoendemic areas
      with different transmission levels: two localities in northwestern Brazil
      (Ariquemes and Porto Velho) and a village in Madagascar (Ankazobe). A total of 89
      DNA samples were analyzed by amplification of polymorphic domains from genes
      encoding merozoite surface antigens 1 and 2 (MSP-1, MSP-2) and thrombospondin
      related anonymous protein (TRAP) and by hybridization with allelic-family
      specific probes or random-fragment-length polymorphism (RFLP). In all three
      localities, extensive polymorphism was observed for each marker, but the MSP-2
      central repeat was the most diverse one. Similar levels of genetic diversity,
      allelic frequency, and infection complexity were observed in the two Brazilian
      localities, although the isolates had been sampled at 2-year intervals,
      suggesting the stability of the infecting parasite populations presenting in
      these regions of the Brazilian Amazon. Unexpectedly, although the entomologic
      inoculation rate was at least 3 times lower in Ankazobe than in the Brazilian
      areas. Malagasi samples appeared more complex than the Brazilian ones. The
      implications of these data with regard to parasite population-dynamics studies
      are discussed.

PMID- 10952274
TI  - Britain's science bounties.

PMID- 10952276
TI  - Canada selects health institutes.

PMID- 10952275
TI  - Prospect of data sharing gives brain mappers a headache.

PMID- 10952277
TI  - UK hopes that big-money deals will attract top talent.

PMID- 10952278
TI  - Science may lose out from sale of 'flying reptile' fossil.

PMID- 10952279
TI  - Researchers criticize response to killer algae.

PMID- 10952281
TI  - Astronomers silenced in star-name wars

PMID- 10952280
TI  - France may bid for fusion reactor

PMID- 10952282
TI  - Berlin genome centre to go ahead.

PMID- 10952283
TI  - Ocean researchers dive to deep-sea stations

PMID- 10952284
TI  - Ecology goes underground.

PMID- 10952285
TI  - How can the developing world protect itself from biotech patent-holders?

PMID- 10952286
TI  - Cost of institute was small change to Roche.

PMID- 10952287
TI  - How neptunium led to the birth of plutonium

PMID- 10952288
TI  - Start making sense

PMID- 10952289
TI  - Taking control

PMID- 10952290
TI  - Biodiversity's ups and downs.

PMID- 10952293
TI  - High-temperature superconductors. Some vortices like it hot

PMID- 10952292
TI  - Molecular switches in metastasis.

PMID- 10952291
TI  - Phase transitions. Catching crystals at birth

PMID- 10952294
TI  - Global change. Iron uncertainty

PMID- 10952295
TI  - Treasure trove for cholera research.

PMID- 10952296
TI  - Taking the Earth's temperature

PMID- 10952297
TI  - Seymour S. Kety (1915-2000).

PMID- 10952298
TI  - Oncogene inactivation in a mouse model.

PMID- 10952299
TI  - Home-site fidelity in migratory honeybees.

PMID- 10952300
TI  - Giant honeybees return to their nest sites.

PMID- 10952301
TI  - DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.
AB  - Here we determine the complete genomic sequence of the gram negative, gamma
      Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp).
      The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp
      that together encode 3,885 open reading frames. The vast majority of recognizable
      genes for essential cell functions (such as DNA replication, transcription,
      translation and cell-wall biosynthesis) and pathogenicity (for example, toxins,
      surface antigens and adhesins) are located on the large chromosome. In contrast,
      the small chromosome contains a larger fraction (59%) of hypothetical genes
      compared with the large chromosome (42%), and also contains many more genes that
      appear to have origins other than the gamma-Proteobacteria. The small chromosome
      also carries a gene capture system (the integron island) and host 'addiction'
      genes that are typically found on plasmids; thus, the small chromosome may have
      originally been a megaplasmid that was captured by an ancestral Vibrio species.
      The V. cholerae genomic sequence provides a starting point for understanding how
      a free-living, environmental organism emerged to become a significant human
      bacterial pathogen.

PMID- 10952302
TI  - Evidence for free precession in a pulsar
AB  - Pulsars are rotating neutron stars that produce lighthouse-like beams of radio
      emission from their magnetic poles. The observed pulse of emission enables their
      rotation rates to be measured with great precision. For some young pulsars, this
      provides a means of studying the interior structure of neutron stars. Most
      pulsars have stable pulse shapes, and slow down steadily (for example, see ref.
      20). Here we report the discovery of long-term, highly periodic and correlated
      variations in both the pulse shape and the rate of slow-down of the pulsar PSR
      B1828-11. The variations are best described as harmonically related sinusoids,
      with periods of approximately 1,000, 500 and 250 days, probably resulting from
      precession of the spin axis caused by an asymmetry in the shape of the pulsar.
      This is difficult to understand theoretically, because torque-free precession of
      a solitary pulsar should be damped out by the vortices in its superfluid
      interior.

PMID- 10952303
TI  - Vortex-like excitations and the onset of superconducting phase fluctuation in
      underdoped La(2-x)Sr(x)CuO4
AB  - Two general features of a superconductor, which appear at the critical
      temperature, are the formation of an energy gap and the expulsion of magnetic
      flux (the Meissner effect). In underdoped copper oxides, there is strong evidence
      that an energy gap (the pseudogap) opens up at a temperature significantly higher
      than the critical temperature (by 100-220 K). Certain features of the pseudogap
      suggest that it is closely related to the gap that appears at the critical
      temperature (for example, the variation of the gap magnitudes around the Fermi
      surface and their maximum amplitudes are very similar). However, the Meissner
      effect is absent in the pseudogap state. The nature of the pseudogap state, and
      its relation (if any) to the superconducting state are central issues in
      understanding copper oxide superconductivity. Recent evidence suggests that, in
      the underdoped regime, the Meissner state is destroyed above the critical
      temperature by strong phase fluctuations (as opposed to a vanishing of the
      superfluid density). Here we report evidence for vortices (or vortex-like
      excitations) in La(2-x)Sr(x)CuO4 at temperatures significantly above the critical
      temperature. A thermal gradient is applied to the sample in a magnetic field.
      Vortices are detected by the large transverse electric field produced as they
      diffuse down the gradient (the Nernst effect). We find that the Nernst signal is
      anomalously enhanced at temperatures as high as 150 K.

PMID- 10952304
TI  - Pixel switching of epitaxial Pd/YHx/CaF2 switchable mirrors
AB  - Exposure of rare-earth films to hydrogen can induce a metal-insulator transition,
      accompanied by pronounced optical changes. This 'switchable mirror' effect has
      received considerable attention from theoretical, experimental and technological
      points of view. Most systems use polycrystalline films, but the synthesis of
      yttrium-based epitaxial switchable mirrors has also been reported. The latter
      form an extended self-organized ridge network during initial hydrogen loading,
      which results in the creation of micrometre-sized triangular domains. Here we
      observe homogeneous and essentially independent optical switching of individual
      domains in epitaxial switchable mirrors during hydrogen absorption. The optical
      switching is accompanied by topographical changes as the domains sequentially
      expand and contract; the ridges block lateral hydrogen diffusion and serve as a
      microscopic lubricant for the domain oscillations. We observe the correlated
      changes in topology and optical properties using in situ atomic force and optical
      microscopy. Single-domain phase switching is not observed in polycrystalline
      films, which are optically homogeneous. The ability to generate a tunable, dense
      pattern of switchable pixels is of technological relevance for solid-state
      displays based on switchable mirrors.

PMID- 10952305
TI  - Electrostatic trapping of ammonia molecules
AB  - The ability to cool and slow atoms with light for subsequent trapping allows
      investigations of the properties and interactions of the trapped atoms in
      unprecedented detail. By contrast, the complex structure of molecules prohibits
      this type of manipulation, but magnetic trapping of calcium hydride molecules
      thermalized in ultra-cold buffer gas and optical trapping of caesium dimers
      generated from ultra-cold caesium atoms have been reported. However, these
      methods depend on the target molecules being paramagnetic or able to form through
      the association of atoms amenable to laser cooling, respectively, thus
      restricting the range of species that can be studied. Here we describe the
      slowing of an adiabatically cooled beam of deuterated ammonia molecules by time
      varying inhomogeneous electric fields and subsequent loading into an
      electrostatic trap. We are able to trap state-selected ammonia molecules with a
      density of 10(6) cm(-3) in a volume of 0.25 cm3 at temperatures below 0.35 K. We
      observe pronounced density oscillations caused by the rapid switching of the
      electric fields during loading of the trap. Our findings illustrate that polar
      molecules can be efficiently cooled and trapped, thus providing an opportunity to
      study collisions and collective quantum effects in a wide range of ultra-cold
      molecular systems.

PMID- 10952306
TI  - Quasi-planar nucleus structure in apoferritin crystallization.
AB  - First-order phase transitions of matter, such as condensation and
      crystallization, proceed through the formation and subsequent growth of 'critical
      nuclei' of the new phase. The thermodynamics and kinetics of the formation of
      these critical nuclei depend on their structure, which is often assumed to be a
      compact, three-dimensional arrangement of the constituent molecules or atoms.
      Recent molecular dynamics simulations have predicted compact nucleus structures
      for matter made up of building blocks with a spherical interaction field, whereas
      strongly anisotropic, dipolar molecules may form nuclei consisting of single
      chains of molecules. Here we show, using direct atomic force microscopy
      observations, that the near-critical-size clusters formed during the
      crystallization of apoferritin, a quasi-spherical protein, and which are
      representative of the critical nucleus of this system, consist of planar arrays
      of one or two monomolecular layers that contain 5-10 rods of up to 7 molecules
      each. We find that these clusters contain between 20 and 50 molecules each, and
      that the arrangement of the constituent molecules is identical to that found in
      apoferritin crystals. We anticipate that similarly unexpected critical nucleus
      structures may be quite common, particularly with anisotropic molecules,
      suggesting that advanced nucleation theories should treat the critical nucleus
      structure as a variable.

PMID- 10952307
TI  - Marine control of biological production in the eastern equatorial Pacific Ocean.
AB  - The eastern equatorial Pacific Ocean is the site of approximately 20-50% of new
      biological production in the global oceans. This region is also responsible for
      the greatest efflux of CO2 from oceans to the atmosphere. New production, which
      fixes carbon in response to external inputs of nutrients as opposed to supply
      from local nutrient recycling, is thought to modulate the CO2 release. But what
      controls new production in this region is less clear. Here we present a
      quantitative reconstruction of biological production in the surface ocean for
      this region over the past 130,000 years, which shows that the equatorial Pacific
      Ocean exhibits higher-frequency variations than the South Equatorial Current.
      Comparison of these records with palaeotemperature reconstructions indicates that
      atmospherically driven mechanisms--such as aeolian flux of iron or wind-driven
      changes in upwelling rate of nutrient-rich waters--are unlikely to have
      influenced longer-term rates of production in this region. Instead, biological
      production appears to be governed by changes in ocean circulation and the
      chemical composition of upwelled water.

PMID- 10952308
TI  - Annual modulation of triggered seismicity following the 1992 Landers earthquake
      in California
AB  - The mechanism responsible for the triggering of earthquakes remains one of the
      least-understood aspects of the earthquake process. The magnitude-7.3 Landers,
      California earthquake of 28 June 1992 was followed for several weeks by triggered
      seismic activity over a large area, encompassing much of the western United
      States. Here we show that this triggered seismicity marked the beginning of a
      five-year trend, consisting of an elevated microearthquake rate that was
      modulated by an annual cycle, decaying with time. The annual cycle is mainly
      associated with several hydrothermal or volcanic regions where short-term
      triggering was also observed. These data indicate that the Landers earthquake
      produced long-term physical changes in these areas, and that an environmental
      source of stress--plausibly barometric pressure--might be responsible for the
      annual variation.

PMID- 10952309
TI  - Ocean circulation off east Antarctica affects ecosystem structure and sea-ice
      extent.
AB  - Sea ice and oceanic boundaries have a dominant effect in structuring Antarctic
      marine ecosystems. Satellite imagery and historical data have identified the
      southern boundary of the Antarctic Circumpolar Current as a site of enhanced
      biological productivity. Meso-scale surveys off the Antarctic peninsula have
      related the abundances of Antarctic krill (Euphausia superba) and salps (Salpa
      thompsoni) to inter-annual variations in sea-ice extent. Here we have examined
      the ecosystem structure and oceanography spanning 3,500 km of the east Antarctic
      coastline, linking the scales of local surveys and global observations. Between
      80 degrees and 150 degrees E there is a threefold variation in the extent of
      annual sea-ice cover, enabling us to examine the regional effects of sea ice and
      ocean circulation on biological productivity. Phytoplankton, primary
      productivity, Antarctic krill, whales and seabirds were concentrated where winter
      sea-ice extent is maximal, whereas salps were located where the sea-ice extent is
      minimal. We found enhanced biological activity south of the southern boundary of
      the Antarctic Circumpolar Current rather than in association with it. We propose
      that along this coastline ocean circulation determines both the sea-ice
      conditions and the level of biological productivity at all trophic levels.

PMID- 10952310
TI  - Diversity peaks at intermediate productivity in a laboratory microcosm.
AB  - The species diversity of natural communities is often strongly related to their
      productivity. The pattern of this relationship seems to vary: diversity is known
      to increase monotonically with productivity, to decrease monotonically with
      productivity, and to be unimodally related to productivity, with maximum
      diversity occurring at intermediate levels of productivity. The mechanism
      underlying these patterns remains obscure, although many possibilities have been
      suggested. Here we outline a simple mechanism--involving selection in a
      heterogeneous environment--to explain these patterns, and test it using
      laboratory cultures of the bacterium Pseudomonas fluorescens. We grew diverse
      cultures over a wide range of nutrient concentrations, and found a strongly
      unimodal relationship between diversity and productivity in heterogeneous, but
      not in homogeneous, environments. Our result provides experimental evidence that
      the unimodal relationship often observed in natural communities can be caused by
      selection for specialized types in a heterogeneous environment.

PMID- 10952311
TI  - Herbivory-induced volatiles elicit defence genes in lima bean leaves.
AB  - In response to herbivore damage, several plant species emit volatiles that
      attract natural predators of the attacking herbivores. Using spider mites
      (Tetranychus urticae) and predatory mites (Phytoseiulus persimilis), it has been
      shown that not only the attacked plant but also neighbouring plants are affected,
      becoming more attractive to predatory mites and less susceptible to spider mites.
      The mechanism involved in such interactions, however, remains elusive. Here we
      show that uninfested lima bean leaves activate five separate defence genes when
      exposed to volatiles from conspecific leaves infested with T. urticae, but not
      when exposed to volatiles from artificially wounded leaves. The expression
      pattern of these genes is similar to that produced by exposure to jasmonic acid.
      At least three terpenoids in the volatiles are responsible for this gene
      activation; they are released in response to herbivory but not artificial
      wounding. Expression of these genes requires calcium influx and protein
      phosphorylation/dephosphorylation.

PMID- 10952312
TI  - Genetic and epigenetic mechanisms contribute to motor neuron pathfinding.
AB  - Many lines of evidence indicate that genetically distinct subtypes of motor
      neurons are specified during development, with each type having characteristic
      properties of axon guidance and cell-body migration. Motor neuron subtypes
      express unique combinations of LIM-type homeodomain factors that may act as
      intrinsic genetic regulators of the cytoskeletal events that mediate cell
      migration, axon navigation or both. Although experimentally displaced motor
      neurons can pioneer new routes to their targets, in many cases the axons of motor
      neurons in complete isolation from their normal territories passively follow
      stereotypical pathways dictated by the environment. To investigate the
      nonspecific versus genetically controlled regulation of motor connectivity we
      forced all motor neurons to express ectopically a LIM gene combination
      appropriate for the subgroup that innervates axial muscles. Here we show that
      this genetic alteration is sufficient to convert the cell body settling pattern,
      gene-expression profile and axonal projections of all motor neurons to that of
      the axial subclass. Nevertheless, elevated occupancy of the axial pathway can
      override their genetic program, causing some axons to project to alternative
      targets.

PMID- 10952313
TI  - An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse
      erythroid cells.
AB  - GATA-1 is a tissue-specific transcription factor that is essential for the
      production of red blood cells. Here we show that overexpression of GATA-1 in
      erythroid cells inhibits their differentiation, leading to a lethal anaemia.
      Using chromosome-X-inactivation of a GATA-1 transgene and chimaeric animals, we
      show that this defect is intrinsic to erythroid cells, but nevertheless cell
      nonautonomous. Usually, cell nonautonomy is thought to reflect aberrant gene
      function in cells other than those that exhibit the phenotype. On the basis of
      our data, we propose an alternative mechanism in which a signal originating from
      wild-type erythroid cells restores normal differentiation to cells overexpressing
      GATA-1 in vivo. The existence of such a signalling mechanism indicates that
      previous interpretations of cell-nonautonomous defects may be erroneous in some
      cases and may in fact assign gene function to incorrect cell types.

PMID- 10952314
TI  - Different initiation of pre-TCR and gammadeltaTCR signalling.
AB  - Lineage choice is of great interest in developmental biology. In the immune
      system, the alphabeta and gammadelta lineages of T lymphocytes diverge during the
      course of the beta-, gamma- and delta-chain rearrangement of T-cell receptor
      (TCR) genes that takes place within the same precursor cell and which results in
      the formation of the gammadeltaTCR or pre-TCR proteins. The pre-TCR consists of
      the TCRbeta chain covalently linked to the pre-TCRalpha protein, which is present
      in immature but not in mature T cells which instead express the TCRalpha chain.
      Animals deficient in pre-TCRalpha have few alphabeta lineage cells but an
      increased number of gammadelta T cells. These gammadelta T cells exhibit more
      extensive TCRbeta rearrangement than gammadelta T cells from wild-type mice.
      These observations are consistent with the idea that different signals emanating
      from the gammadeltaTCR and pre-TCR instruct lineage commitment. Here we show, by
      using confocal microscopy and biochemistry to analyse the initiation of
      signalling, that the pre-TCR but not the gammadeltaTCR colocalizes with the
      p56lck Src kinase into glycolipid-enriched membrane domains (rafts) apparently
      without any need for ligation. This results in the phosphorylation of CD3epsilon
      and Zap-70 signal transducing molecules. The results indicate clear differences
      between pre-TCR and gammadeltaTCR signalling.

PMID- 10952315
TI  - Distinct beta-catenins mediate adhesion and signalling functions in C. elegans.
AB  - In flies and vertebrates, Armadillo/beta-catenin forms a complex with Tcf/Lef-1
      transcription factors, serving as an essential co-activator to mediate Wnt
      signalling. It also associates with cadherins to mediate adhesion. In
      Caenorhabditis elegans, three putative beta-catenin homologues have been
      identified: WRM-1, BAR-1 and HMP-2. WRM-1 and the Tcf homologue POP-1 mediate Wnt
      signalling by a mechanism that has challenged current views of the Wnt pathway.
      Here we show that BAR-1 is the only beta-catenin homologue that interacts
      directly with POP-1. BAR-1 mediates Wnt signalling by forming a BAR-1/POP-1
      bipartite transcription factor that activates expression of Wnt target genes such
      as the Hox gene mab-5. HMP-2 is the only beta-catenin homologue that interacts
      with the single cadherin of C. elegans, HMR-1. We conclude that a canonical Wnt
      pathway exists in C. elegans. Furthermore, our analysis shows that the functions
      of C. elegans beta-catenins in adhesion and in signalling are performed by
      separate proteins.

PMID- 10952316
TI  - Genomic analysis of metastasis reveals an essential role for RhoC.
AB  - The most damaging change during cancer progression is the switch from a locally
      growing tumour to a metastatic killer. This switch is believed to involve
      numerous alterations that allow tumour cells to complete the complex series of
      events needed for metastasis. Relatively few genes have been implicated in these
      events. Here we use an in vivo selection scheme to select highly metastatic
      melanoma cells. By analysing these cells on DNA arrays, we define a pattern of
      gene expression that correlates with progression to a metastatic phenotype. In
      particular, we show enhanced expression of several genes involved in
      extracellular matrix assembly and of a second set of genes that regulate, either
      directly or indirectly, the actin-based cytoskeleton. One of these, the small
      GTPase RhoC, enhances metastasis when overexpressed, whereas a dominant-negative
      Rho inhibits metastasis. Analysis of the phenotype of cells expressing dominant
      negative Rho or RhoC indicates that RhoC is important in tumour cell invasion.
      The genomic approach allows us to identify families of genes involved in a
      process, not just single genes, and can indicate which molecular and cellular
      events might be important in complex biological processes such as metastasis.

PMID- 10952317
TI  - Molecular classification of cutaneous malignant melanoma by gene expression
      profiling.
AB  - The most common human cancers are malignant neoplasms of the skin. Incidence of
      cutaneous melanoma is rising especially steeply, with minimal progress in non
      surgical treatment of advanced disease. Despite significant effort to identify
      independent predictors of melanoma outcome, no accepted histopathological,
      molecular or immunohistochemical marker defines subsets of this neoplasm.
      Accordingly, though melanoma is thought to present with different 'taxonomic'
      forms, these are considered part of a continuous spectrum rather than discrete
      entities. Here we report the discovery of a subset of melanomas identified by
      mathematical analysis of gene expression in a series of samples. Remarkably, many
      genes underlying the classification of this subset are differentially regulated
      in invasive melanomas that form primitive tubular networks in vitro, a feature of
      some highly aggressive metastatic melanomas. Global transcript analysis can
      identify unrecognized subtypes of cutaneous melanoma and predict experimentally
      verifiable phenotypic characteristics that may be of importance to disease
      progression.

PMID- 10952318
TI  - A chromatin remodelling complex involved in transcription and DNA processing.
AB  - The packaging of the eukaryotic genome in chromatin presents barriers that
      restrict the access of enzymes that process DNA. To overcome these barriers,
      cells possess a number of multi-protein, ATP-dependent chromatin remodelling
      complexes, each containing an ATPase subunit from the SNF2/SWI2 superfamily.
      Chromatin remodelling complexes function by increasing nucleosome mobility and
      are clearly implicated in transcription. Here we have analysed SNF2/SWI2- and
      ISWI-related proteins to identify remodelling complexes that potentially assist
      other DNA transactions. We purified a complex from Saccharomyces cerevisiae that
      contains the Ino80 ATPase. The INO80 complex contains about 12 polypeptides
      including two proteins related to the bacterial RuvB DNA helicase, which
      catalyses branch migration of Holliday junctions. The purified complex remodels
      chromatin, facilitates transcription in vitro and displays 3' to 5' DNA helicase
      activity. Mutants of ino80 show hypersensitivity to agents that cause DNA damage,
      in addition to defects in transcription. These results indicate that chromatin
      remodelling driven by the Ino80 ATPase may be connected to transcription as well
      as DNA damage repair.

PMID- 10952320
TI  - Mahoney centre set to tackle brain cancer head on.

PMID- 10952319
TI  - Collaborations prepare to untangle the circuitry of the brain.

PMID- 10952321
TI  - Kangaroo versus porcine aortic valve tissue--valve geometry morphology, tensile
      strength and calcification potential.
AB  - OBJECTIVE: Valve related factors and patient related factors are responsible for
      calcification of valvular bioprostheses. Recent studies showed different donor
      and recipient species have different influences on the total calcification rate
      of bioprostheses. This study was performed to evaluate and compare Kangaroo
      aortic valve leaflets with porcine aortic valve leaflets. Experimental design.
      Prospective study. Setting. Cardio-thoracic experimental research of a university
      department. MATERIALS AND METHODS: Glutaraldehyde-fixed Kangaroo and porcine
      valve leaflets were evaluated in vitro according to valve geometry (internal
      diameter and leaflet thickness), morphology (light and electron microscopy) and
      tensile strength. In vivo evaluation consisted of implantation in a rat model for
      8 weeks, Von Kossa stain for calcium and atomic absorption spectrophotometry for
      total extractable calcium content. RESULTS: Kangaroo valves indicated a smaller
      internal valve diameter as well as a thinner valve leaflet (p<0.01, ANOVA) at
      corresponding body weight, less proteoglycan spicules in the fibrosa, increased
      elasticity (p<0.05) and low calcification potential (p<0.01, confidence interval
      95%). CONCLUSIONS: Kangaroo aortic valve leaflets have different valvular
      qualities compared to porcine valve tissue. Kangaroo valve leaflets are
      significantly superior to porcine valve leaflets as far as calcification is
      concerned. These results are encouraging and suggest further in vivo evaluation
      in a larger animal model before clinical application can be considered.

PMID- 10952322
TI  - Postinfarct refractory right ventricle: right ventricular exclusion. A possible
      option to mechanical cardiac support, in patients unsuitable for heart
      transplant.
AB  - BACKGROUND: Postbypass refractory right ventricle (RRV) may develop due to right
      ventricular (RV) ischemia or infarction. In cases with RV infarction, recovery is
      often prolonged and salvage rate is extremely poor. In this retrospective study,
      we have examined the role of right ventricular exclusion (RVE), as a possible
      option to conventional weaning or bridging to heart transplant (B-HTX), in
      patients who were unsuitable for heart transplant. METHODS: During last 5 years,
      cumulative incidence of postbypass refractory circulatory failure (RCF) in our
      adult patients was 0.39% (26/6542). This problem was caused by a RRV in 17 (65%)
      patients. After CABG, these patients developed a grossly distended and poorly
      contracting RV (RVEDV: 330-400 ml, RVEF: 0-10%), high central venous pressure (>
      or =18 mmHg) and an inadequate aortic pressure for weaning off cardiopulmonary
      bypass. Three patients, who were unacceptable for HTX under UNOS program (age >65
      years), were weaned off bypass after RVE, and remaining patients with RVAD (n=3)
      or BiVAD support, depending upon their concomitant moderate or poor left
      ventricular performance. RESULTS: The significant predictors of RRV by univariate
      analysis were; 2nd or 3rd redo CABG for a recent myocardial infarction, and
      failed graft angioplasty. Hospital mortality (14-60 days) was 0/3, 3/3 and 3/11
      for the patients weaned off with RVE, RVAD and BiVAD respectively. At 3 years,
      overall salvage rate was 9/17 (RVE: 3/3, BiVAD B-HTX 4/6 + 2 weaned with BiVAD
      support). CONCLUSION: Right ventricular exclusion is a possible option to
      conventional B-HTX with mechanical support, in patients who develop postinfarct
      RRV and are unsuitable for transplant.

PMID- 10952323
TI  - Improved blood cellular biocompatibility with heparin coated circuits during
      cardiopulmonary bypass.
AB  - BACKGROUND: The clinical use of heparinized surfaces in the extracorporeal
      circuit was studied to find out if there was any blood cell rheologic benefit to
      support its use in routine low risk cardiac surgery. METHODS: In a prospective
      single blind study, 39 patients were operated upon with the heart lung machine
      for angina pectoris by coronary bypass grafting and were randomized to a control
      group or a heparin group. Blood cell rheology was analysed using the St. George
      filtrometer where damage to the red blood cells and white blood cells was
      estimated by assessing deformability reductions, transit, time increases and
      clogging rate and clogging particle changes. RESULTS: At the end of
      cardiopulmonary bypass, in the heparin group, the red cell filterability (rFR)
      and the white cell filterability (WFR) were 8% better than in the control group
      (p=0.0079 and p=0.027 respectively). The red cell transit time was 19% slower in
      the control group (p=0.0351). The red cell clogging rate (RCR) and clogging
      particles (RCP) were significantly lower in the heparin group (p=0.0212 and
      p=0.0409 respectively. The white cell clogging rate (WCR) and clogging particles
      (WCP) showed a similar pattern. CONCLUSIONS: In spite of these significant
      differences the clinical outcome was similar in the groups. Thus heparin coating
      of the extracorporeal circuit reduces blood cell rheologic damage significantly
      in low risk patients undergoing routine bypass surgery for angina but this use
      did not lead to any clinical benefit postoperatively. Therefore the use of such
      circuits for routine low risk cardiac surgery cannot be recommended.

PMID- 10952324
TI  - The effect of short-term coronary perfusion using oxygenated diluted blood
      following cold storage for long-term heart preservation.
AB  - BACKGROUND: The aim of this study was to compare the results obtained from the
      use of both University of Wisconsin (UW) solution and diluted blood in short-term
      coronary perfusion following 12-hour cold storage. METHODS: Following coronary
      vascular washout of adult mongrel dogs with the UW solution, the heart was
      excised and immersed in a cold (4 degrees C) UW solution for 12 hours followed by
      1-hour of coronary perfusion. Two different solutions were used for the coronary
      perfusion; a 4 degrees C oxygenated UW solution (Group U, n=7) and 15 degrees C
      oxygenated diluted blood (Group B, n=7). Myocardial high energy phosphate (HEP)
      levels, tissue water content (TWC), interstitial tissue space (ITS) rates and
      histological findings were evaluated at 0- and 12-hour cold storage and also
      following coronary perfusion. The preserved graft was then evaluated through
      orthotopic transplantation. The control group in this experiment consisted of
      seven hearts transplanted after 12-hour cold storage without coronary perfusion.
      RESULTS: Myocardial HEP levels significantly decreased after 12-hour cold
      storage. The recovery rate of myocardial HEP levels after coronary perfusion was
      significantly (p<0.05) higher in Group B than in Group U. The increase of
      myocardial TWC during coronary perfusion was significantly (p<0.01) higher in
      Group B than in Group U. After 1-hour coronary perfusion, the subendocardial ITS
      rate was significantly (p<0.01) higher compared with the value at 0-hour cold
      storage in Group U, whereas it demonstrated no significant change in Group B. PAS
      stain revealed the glycogen content of the subendocardial tissues was higher in
      Group B than in Group U. The recovery rate of hemodynamic parameters 2 hours
      after heart transplantation was higher in Group U and significantly (p<0.05)
      higher in Group B than in the control. CONCLUSIONS: Myocardial HEP levels
      recovered significantly after additional coronary perfusion. Though the UW
      solution prevented myocardial cellular edema, subendocardial perfusion was
      incomplete and the recovery rate of myocardial HEP levels was lower, suggesting
      that diluted blood may become the solution of choice as a perfusate.

PMID- 10952325
TI  - The effect of carbon dioxide tension on cerebral circulation during hypothermic
      selective cerebral perfusion.
AB  - BACKGROUND: Some reports have observed the response of cerebral blood flow to
      PaCO2 during hypothermic cardiopulmonary bypass. We studied the effect of PaCO2
      on the cerebral circulation during hypothermic selective cerebral perfusion.
      METHODS: Between June 1992 and January 1998, 35 patients underwent aortic arch
      grafting using hypothermic selective cerebral perfusion (20 degrees C). In the
      earlier four patient (Group 1), carbon dioxide gas was not added. In the latter
      31 patient (Group 2), carbon dioxide gas was added to the cerebral perfusion. The
      hemodynamics and rates of change in cerebral oxygen saturation were evaluated.
      RESULTS: In Group 1, the index of cerebral arterial resistance was 9.2+/-2.2 at
      the start of selective cerebral perfusion and increased to 15.7+/-0.1 at the re
      warming stage (p<0.05), and there was a significant decrease in cerebral oxygen
      saturation at the re-warming stage (p<0.001). In Group 2, the index of cerebral
      arterial resistance was 4.7+/-1.7 at the start of selective cerebral perfusion
      and 4.3+/-1.5 at the re-warming stage, a non-significant change. The change in
      cerebral oxygen saturation was also nonsignificant between the start of selective
      cerebral perfusion and the re-warming stage. Among the neurological outcomes,
      there was only one small cerebral infarction in Group 2; however, no delayed
      conscious recovery was observed. CONCLUSIONS: The addition of CO2 to cerebral
      perfusion was a factor in inhibiting the increase in the cerebral vascular
      resistance at the re-warming stage.

PMID- 10952326
TI  - Transfusion-associated graft-versus-host disease with transfusion practice in
      cardiac surgery.
AB  - BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) in
      immunocompetent patients has still been underdiagnosed and underreported. Risk of
      TA-GVHD caused by transfusion practice in cardiac surgery should be appropriately
      recognized. METHODS: The correlation of TA-GVHD with transfusion practice in
      cardiac surgery was analyzed from our 17-year clinical experience. We
      retrospectively reviewed 2,686 consecutive adult patients who underwent cardiac
      surgery between 1980 and 1996. Classified according to transfusion practice, 847
      patients (32%) received nonirradiated fresh homologous whole blood (mean per
      patient, 5+/-2 units) with or without other blood components; 592 patients (22%)
      nonirradiated stored RBCs older than 7 days (4+/-2), and 551 patients (21%)
      received irradiated homologous blood including, fresh whole blood (2+/-1), RBCs
      (4+/-1), and PCs (8+/-3), respectively. The remaining 696 patients (25%), did not
      require homologous transfusion. RESULTS: Four of 847 patients who received
      nonirradiated fresh homologous whole blood (< or =48 hours after donation)
      developed TA-GVHD. TA-GVHD did not occur in other patients. CONCLUSIONS: Our
      local experience demonstrates the incidence of TA-GVHD in patients who received
      fresh homologous whole blood in cardiac surgery was much higher, compared with
      previous reports. This result suggests that the frequency of TA-GVHD is nearly
      similar to the value calculated from the proportion of HLA haplotypes in the
      population.

PMID- 10952327
TI  - Usefulness of transesophageal echocardiography during open heart surgery of
      mitral stenosis.
AB  - BACKGROUND: The aim of this study was to verify if the use of intraoperative
      transesophageal echocardiography (TEE), by detecting mitral insufficiency or
      residual stenosis during surgery, may improve medium term results in patients
      with severe mitral stenosis who undergo open heart valvuloplasty. METHODS: This
      prospective study included twenty-two patients (20 women and 2 men) with a mean
      age of 49+/-13 years with severe mitral stenosis. Mean follow-up was 32 months
      (range 12-55 months). All the patients underwent transthoracic echocardiography
      (TrE) before surgery and intraoperative TEE. Before surgery the mean transmitral
      gradient was 11+/-6.8 mmHg, the mean pressure half time (PHT) area was 0.89+/
      0.19 cm2, the mean echo score was 8.9+/-2.2. Intraoperative TEE before the repair
      showed a mean echo score of 7.9+/-1.8. RESULTS: Two patients with unsatisfactory
      repair at TEE underwent immediate valve replacement. In the remaining patients,
      mean transmitral gradient and PHT valve area before discharge was 5.2+/-3 mmHg
      and 2.5 cm2. No patients had more than trivial mitral regurgitation. During the
      follow-up two patients had to be reoperated. Patients with poor immediate (2
      patients) or medium term results (2 patients), had a mean echocardiographic score
      of 12.24, while patients with a satisfactory medium term outcome had a mean score
      of 7.27 (p<0.001). CONCLUSIONS: Intraoperative TEE may guide the surgeon in the
      assessment of valvuloplasty. However the absence of mitral regurgitation after
      repair and at discharge cannot predict the medium term results, which are related
      to the degree of the disease of the mitral valve.

PMID- 10952328
TI  - Ross procedure for complex left ventricular outflow tract obstruction.
AB  - BACKGROUND: Complex left ventricular outflow tract (LVOT) obstruction in children
      continues to pose a significant therapeutic challenge to cardiac surgeons. The
      Ross procedure, in combination with resection of subaortic stenosis or a Konno
      type septal incision, is an important option for these difficult patients.
      METHODS: Recently two children aged 14 and 5 years with LVOT obstruction
      involving combined subaortic and valvar stenosis underwent surgical correction
      using the pulmonary autograft. Clinical presentation, operative technique,
      outcome and intermediate follow-up are detailed. RESULTS: One patient had
      resection of an isolated subaortic membrane in combination with a pulmonary
      autograft and the second a Ross Konno procedure. Postoperative hospital stays
      were without complication. Both patients were discharged at 5 days and have no
      significant obstruction nor semilunar valve insufficiency at 3 years' follow-up.
      CONCLUSIONS: Pulmonary autografts can be used in combination with resection of
      subaortic tissue or a septal incision for reconstruction of complex left
      ventricular outflow tract obstruction. This technique renders excellent short
      term valve function, relief of obstruction, avoids anticoagulation and provides
      potential for future growth.

PMID- 10952329
TI  - Ruptured mitral valve aneurysm in a patient with quadricuspid aortic valve.
AB  - Mitral aneurysm is commonly associated with infectious endocarditis of the aortic
      valve. In rare instances, it is associated with other underlying inflammatory or
      metabolic disorders. A 62-year-old man with mitral valve insufficiency with
      moderate aortic valve insufficiency underwent operation. Operative findings were
      the ruptured aneurysm of the mitral valve in association with the calcified
      quadricuspid aortic valve. There was no evidence of infection in the mitral valve
      and the aortic valve. The mitral valve was repaired, the aortic valve replaced,
      and Cox Maze procedure added. A rare combination of mitral and aortic valve
      lesions without endocarditis suggested that mechanical stress alone may induce
      mitral valve aneurysm.

PMID- 10952331
TI  - Re-use of left internal thoracic artery for redo operation after MIDCAB.
AB  - We report a case of recycling of left internal thoracic artery (LITA) in situ in
      reoperation of coronary artery bypass grafting. A 41-year-old male, who has poor
      controlled hypercholesterolemia, was bypassed LITA to the left anterior
      descending artery (LAD) in minimally invasive direct coronary artery bypass
      (MIDCAB) manner at the other hospital. Four months later, he felt short of breath
      on effort. Coronary angiogram showed stenoses of the left main trunk and
      anastomosis site of the LITA. At redo operation, we skeletonised the LITA and
      reused it in situ to the LAD. Using the skeletonised method for re-harvesting
      LITA made the graft reach a more distal portion without tension. He is doing well
      at 18 months after surgery. In selected patients, recycling of the used arterial
      grafts can reserve other arterial grafts for redo operations in the future.

PMID- 10952330
TI  - Swinging motion of intimal flap through the aortic valve in acute aortic
      dissection.
AB  - The purpose of this article is to present a very rare case of Stanford type A
      acute aortic dissection featuring a swinging motion of the cylinder-shaped
      intimal flap through the aortic valve. The patient was a 62-year-old male
      suffering from severe cardiogenic shock. A transthoracic echocardiogram revealed
      aortic dissection and severe aortic regurgitation. A transesophageal
      echocardiogram demonstrated that the aortic dissection in the ascending aorta was
      circumferential and the proximal portion of the intimal flap was swinging through
      the aortic valve, ie., falling into the left ventricle during the diastolic phase
      and being ejected back into the ascending aorta during the systolic phase. An
      emergency graft replacement of the ascending aorta was performed. During
      ventricular fibrillation under total cardiopulmonary bypass, we performed cardiac
      massage to prevent myocardial ischemia, because blood flow from a heart lung
      machine inverted the intimal flap, which might have disturbed the coronary
      circulation. The patient's postoperative course was uneventful, and his
      postoperative echocardiogram revealed only a trace of regurgitant flow through
      the aortic valve. Back-and-forth movement of the cylinder-shaped intima requires
      coexistence of the following three conditions: severe aortic regurgitation,
      circumferential dissection, and complete transection of the intimal flap. We
      conclude that this movement of the intimal flap should be regarded as one of the
      most serious complications leading rapidly to cardiogenic shock. From a surgical
      point of view, it is most important to prevent myocardial ischemia during
      cardiopulmonary bypass especially in cases in which ventricular fibrillation has
      occurred. We describe the ways to prevent myocardial ischemia in this rare
      situation.

PMID- 10952332
TI  - Combined repair of adult coarctation of the aorta and aortic valvular stenosis.
AB  - A 57-year-old man with a high-grade aortic stenosis and aortic coarctation was
      treated with concomitant valve replacement and insertion of a conduit from the
      ascending aorta to the retrocardiac descending aorta via the left pleura. Because
      heart failure has been reported shortly after cardiopulmonary bypass using this
      technique, the conduit was initially clamped until the postrepair haemodynamics
      was stable. Computed tomography after 14 months verified patency of the shunt.

PMID- 10952333
TI  - Pericardial patch for rapid and effective hemostasis of cardioplegia injection
      site.
AB  - Cardioplegia injection site may be the source of serious haemorrhagic
      complications either intraoperatively or during the early postoperative period.
      Here we describe a simple technique that allows a rapid control of hemostasis at
      this site. An autologous pericardial patch is used to repair and strengthen the
      aortic wall.

PMID- 10952334
TI  - Intraoperative autotransfusion for repair of unruptured aneurysms of the
      infrarenal abdominal aorta. A multicenter study of 203 patients. Association
      Universitaire de Recherche en Chirurgie (AURC).
AB  - BACKGROUND: The goals of this study were to evaluate the costs and savings of
      intra- and postoperative blood transfusions as well as the potential biological
      modifications associated with the use of intraoperative blood salvage. METHODS:
      Intraoperative autotransfusion (IOAT) with wash-out was prospectively studied
      during the repair of unruptured aneurysms of infrarenal abdominal aorta in 203
      patients operated on in 13 institutions. RESULTS: The mean quantity of blood
      retrieved was 688+/-468 mL The mean quantity of blood derivatives and
      intraoperative solutes used for repletion was 4,261 ml, ranging from 1,723 ml
      between days 0 to D2 to 562 ml from D3 to D8. Ninety-eight patients did not
      receive any blood derivatives at all. Thirty-five patients received plasma to
      correct coagulation factors. The quantity of autotransfused globular concentrate
      was less than 500 ml in 89 patients. CONCLUSIONS: IOAT precluded the need for
      transfusion of homologous globular concentrates, particularly in those patients
      who had bled most. On average, more than two globular concentrates were
      recuperated. Use of IOAT led to financial savings. Perioperative bleeding is not
      the only factor that intervenes in the decision to transfuse globular
      concentrates. Postoperative dilution is the most important factor as attested by
      the amount of protides and the hematocrit. Coagulation factors are modified but
      remain compatible with normal hematosis in 83% of patients undergoing operation.

PMID- 10952335
TI  - Reoperation for graft failure of femoropopliteal bypass with externally supported
      knitted Dacron prosthesis.
AB  - BACKGROUND: Aggressive reoperation for failing or failed femoropopliteal (FP)
      bypass has been affirmative despite graft material. There has been no report
      regarding results of reoperation for FP bypass with externally supported knitted
      Dacron prosthesis (EXS). The aim of this study is to justify aggressive
      reoperation of FP bypass with EXS and to examine risk factors affecting the
      result of reoperation. METHODS: A retrospective review was performed on 204
      patients undergoing 212 FP bypasses (with EXS between January 1982 and December
      1997 and 34 FP EXSes of 32 patients underwent reoperation for graft failure until
      March 1998. The cumulative graft patency (GP) and limb salvage (LS) rate after
      first reoperation for 34 FP bypass EXS were calculated and the importance of each
      perioperative factor on GP or LS was estimated by uni- and multivariate analysis.
      RESULTS: Reoperated 34 FP EXSes included 12 failing and 22 failed grafts and 14
      limbs with failed grafts underwent reoperation for limb salvage. The GP of 34
      grafts and LS of 14 limbs rate were 58 and 67% at 2 years, respectively.
      Univariate analysis identified graft thrombosis (2 years GP; failing graft:
      failed graft=78: 48%) and continuance of smoking (2 years LS; smoker: non
      smoker=43: 100%) as a significant risk factor of GP and IS, respectively, neither
      of which was significant by multivariate analysis. CONCLUSIONS: Early diagnosis
      and treatment, before graft thrombosis, can lead to superior durability of GP and
      discontinuance of smoking is important for LS.

PMID- 10952336
TI  - Carotid artery injuries and their management.
AB  - BACKGROUND: Major vascular injuries in the region of the neck are most frequently
      the result of penetrating trauma. Evaluation and management of patients with
      injury to Zone II of the neck remains highly controversial. Most studies involve
      small number of patients with a lack of standardization of the nature of the
      injury in reporting outcome. It is the purpose of this study to propose a grading
      scale for vascular injuries in the neck that would allow for more uniform
      reporting of such injuries. METHODS:  EXPERIMENTAL DESIGN: A retrospective review
      of all patients treated for penetrating trauma to the neck was performed and the
      subset of patients with major vascular injuries identified. Data from this group
      of patients are presented. SETTING: Level II urban trauma center. PATIENTS AND
      INTERVENTIONS: During the period July 1984 to June 1994, 107 patients were
      treated for penetrating neck trauma. Injuries to the major arteries of the neck
      were present in 18 of the 107 patients (16.8%). All injuries were graded on the
      developed scale. Management protocol was based on the grade of the injury. Grade
      1 injuries were managed non-operatively with systemic anticoagulation and low
      molecular weight dextran. Grade 2 injuries were treated with primary repair.
      Injuries of Grades 3 and 4 were treated by primary repair or interposition graft.
      Exceptions were isolated injuries of the external carotid artery, which were
      treated by ligation alone. RESULTS: Of the 18 patients with carotid artery
      injuries, 2 had injuries of the external carotid artery, treated with ligation
      alone. The internal carotid artery was injured in 7 cases. An interposition
      saphenous vein/PTFE graft was used in all cases. In 9 cases the common carotid
      artery was injured. Repair was accomplished by a combination of either a primary
      repair or interposition graft. Overall mortality was 3/16 (16.6%). No new or
      worsening of neurologic deficit occurred in any patient. CONCLUSIONS: Carotid
      artery injuries occur in about 17% of patients with penetrating neck trauma. Data
      regarding management and prognosis in these patients are at best concflicting, in
      part, due to lack of a standardized classification system. The proposed grading
      scale is designed to overcome this problem.

PMID- 10952337
TI  - Semiclosed endarterectomy for long superficial femoral artery atherosclerotic
      occlusive disease. One-year angiographic results.
AB  - BACKGROUND: The anatomic results of endarterectomy of long occlusive lesions in
      the superficial femoral artery (SFA) are required for reconsidering this
      procedure and comparing the results with those of newly developed endovascular
      techniques. We designed a prospective study to determine the arteriographic
      findings one year after a successful semiclosed endarterectomy of long occlusive
      lesions in the SFA. METHODS: From January 1995 until July 1996, an endarterectomy
      in the SFA was attempted in 12 successive patients and was successfully performed
      in 10 patients (6 men and 4 women), with an average age of 73 years (range 66 to
      90 years). Indications for successfully performed procedures were claudication in
      6, non healing ulcer in 2, local gangrene in 2 patients. The mean length of the
      occlusion was 17 cm (12-33). Six patients had poor run-off with 0 to 1 patent
      tibial artery. The mean length of the endarterectomised segment was 31 cm (27
      39). An angioscopy and an angiography were performed in all procedures. There
      were no postoperative complications. All patients had an angiography at 12 months
      or before because of ipsilateral disease. Primary angiographic patency was
      defined as patency of the treated artery with stenosis of less than 30%. A short
      stenosis was defined as <5 cm. These lesions were an indication of percutaneous
      balloon angioplasty (PTA) and the final results were listed as secondary patency.
      RESULTS: Angiography revealed 3 patent arteries, 5 short stenosis, 2 long
      stenosis and no occlusions. The primary patency rate was 30% at 12 months. The
      secondary patency was 80% with a mean follow-up of 19 months (ranging from 13 to
      25 months). The mortality and amputation rate at 12 months was nil. CONCLUSIONS:
      Despite a modern intraoperative control, there was a high incidence of restenosis
      after semiclosed endarterectomy performed for long occlusive lesions of the SFA.
      As a result of a close surveillance and PTA, the secondary patency at one year
      was good. Before a widespread use of newly developed endovascular techniques,
      comparative patency studies with the mere endarterectomy should be performed.
      Endarterectomy followed by a PTA in cases of restenosis, is an alternative to
      bypass when the vein is not available.

PMID- 10952338
TI  - The occurrence of the post-thrombotic changes after an acute deep venous
      thrombosis. A prospective two-year follow-up study.
AB  - BACKGROUND: The aim of the study is to investigate the development of subjective
      and objective findings during the first two years after DVT (deep venous
      thrombosis). METHODS: This prospective two-year follow-up study was established
      in Tampere University Hospital in Finland. Twenty-six patients with a two-year
      follow-up after a phlebographically confirmed DVT were followed. Patients were
      treated conventionally with heparin and warfarin. Phlebography was repeated 7
      months after DVT. Color-flow duplex imaging (CFDI) was performed in both legs 7
      and 20 months after DVT. The subjective symptoms in both legs were recorded at
      the beginning and at the end of the follow-up. The development of venous reflux,
      obstruction and subjective symptoms after DVT were studied. RESULTS: 50% of the
      legs with DVT had a pathological (deep reflux or obstructive change) CFDI-finding
      in the popliteal segment after a 20-month follow-up. The pathological findings in
      the control legs were rare. The rate of recanalisation was high. There was no
      difference between calf and more proximal DVTs. Pain (62%), oedema (46%) and
      pigmentation (35%) were common and only 27% of the legs with DVT were
      asymptomatic. CONCLUSIONS: The development of the post-thrombotic syndrome begins
      quite early. The frequency of the subjective symptoms is high. Calf DVT may lead
      to postthrombotic sequelae in the popliteal segment.

PMID- 10952339
TI  - Therapeutic tactics and late results in predominant truncal congenital
      malformation.
AB  - BACKGROUND: Congenital vascular malformations are rare vascular lesions of
      unknown etiology, non-degenerative or of inflammatory nature, which begin during
      embryological development; they are characterized by anomalies of the vascular
      system, apparently due to hemodynamic and metabolic disturbances. METHODS: Our
      diagnostic and therapeutic management in addition to the late results in 60,
      mainly truncal cases, out of 265 congenital vascular malformations, are analyzed
      in the present study. In a 20-year period 25,000 vascular examinations were
      carried out, among which 265 (1.06%) congenital vascular malformations (CVMs)
      were discovered, that is 77% (205/265) extra-truncal venous angiomata and 22.7%
      (60/265) truncal diffuse or localized types. The distribution of the above types
      was: 22 (36.6%) arteriovenous, 30 (50%) venous and 8 (13.4%) lymphatic. RESULTS:
      Surgery was carried out in 48.3% (29/60) of the truncal types of which 37.9% of
      the cases, on average, recurred 8 years later. Of the 22 arteriovenous
      malformations 20 patients were operated on (90%), of whom 35% (7/20) had a
      recurrence; of the 30 venous defects 30% (9/30) were operated on and 44.5% (4/9)
      of these had a recurrence. The recurrence rate rose to 50% (5/10) in cases of
      operative therapy of arteriovenous defects and to 20% (2/10) with combined
      surgical and non surgical methods. The recurrence incidence of venous defects
      with surgical treatment and sclerotherapy was 54.1% (6/11). CONCLUSIONS: Timely
      diagnosis, microsurgical techniques and highly specialized surgical and
      interventional experience are expected to improve these results significantly.

PMID- 10952341
TI  - Rupture of pseudointima in an implanted vascular prosthesis: immunohistological
      study of plasminogen activators and matrix metalloproteinases.
AB  - We investigated late-onset anastomotic stenosis in an implanted prosthetic graft.
      Rupture of the pseudointima and hemorrhaging from the vasa vasorum were observed
      at the border of the collagenous tissue and fibrin layer. An immunohistological
      study showed that the fibrin layer was positive for tPA, but weakly positive for
      PAI-1. Some neutrophils and monocyte/macrophages in the fibrin layer were
      immunostained for tPA, uPA, uPAR, and MMP-1, -2 and -3. Some spindle-shaped cells
      surrounding the graft were immunostained for uPA, uPAR, MMP-1, -2, -3, -7 and -9,
      and TIMP-1 and -2. The endothelial cells of some microvessels were positive for
      MMP-1 and -2, and tPA. Some multi-nucleated giant cells were immunostained for
      MMP-7 and-9, tPA, PAI-1, uPA, and uPAR. Overexpressed MMPs and PAs possibly
      caused instability of the pseudointima.

PMID- 10952340
TI  - Management of inflammatory aneurysm of the infrarenal aorta using retroperitoneal
      exposure, open aneurysmorrhaphy and descending aorta-to-femoral artery bypass.
AB  - The authors present a technique consisting of retroperitoneal exposure, but not
      dissection of the inflammatory aneurysm, anastomosis of a bypass graft through a
      short thoracotomy to the lowermost thoracic aorta, carrying it down
      retroperitoneally to both femoral arteries and under brief occlusion of the
      descending thoracic aorta, opening of the aneurysm and intra-aneurysmal occlusion
      of the inflow and outflow to the aneurysm. An illustrative case is presented.

PMID- 10952342
TI  - Transcatheter embolization of mycotic aneurysm of the subclavian artery with
      metallic coils.
AB  - Mycotic aneurysms of the subclavian artery are rare. This report describes an
      experience of 2 rare cases in which transcatheter embolization with metallic
      coils was performed for the management of these lesions alternative to surgery.
      Two patients who had been treated with chemotherapy for malignant neoplasms were
      diagnosed as having mycotic aneurysms of the left subclavian artery. The causes
      of these lesions were presumed to be the invasion of the arterial wall by the
      pulmonary abscess in case 1, and wound infection after placement of the reservoir
      for intraarterial chemotherapy in case 2. In both cases, proximal and distal
      sites of the aneurysm were embolized with metallic coils. In case 1, the
      vertebral artery was also embolized with Guglielmi detachable coils to avoid
      retrograde blood flow. Both aneurysms were completely occluded by a single
      embolization. In case 1, although weakness and paresthesia of the left hand
      remained, lethal hemoptysis due to aneurysmal fistulization to the lung
      parenchyma ceased. In case 2, no neurological deficit except for mild paresthesia
      in the left thumb had been observed. Both patients died of primary disease 10 and
      5 months after the procedure. Transcatheter embolization is technically feasible
      and effective enough to treat the mycotic aneurysm of the subclavian artery even
      in the situation in which the surgical option seems to be difficult or risky.

PMID- 10952343
TI  - Surgical repair of abdominal aortic or iliac aneurysms associated with treatment
      of urological neoplasias.
AB  - Safe surgical repair of an abdominal aortic aneurysm in conjunction both with
      nephrectomy (for monolateral or bilateral kidney carcinoma) or with radical
      cystectomy and orthotopic urinary diversion (for bladder carcinoma) can be
      performed. These combined surgical procedures can be performed without morbidity
      due to excessive blood loss, increased operative time or vascular graft
      infection. A nephrectomy associated with abdominal aortic aneurysm repair can be
      performed both by a median single surgical approach or by a double one during the
      same intervention. The authors describe and discuss 4 case reports and the
      techniques required for these combined procedures.

PMID- 10952344
TI  - Successful resection of superior mesenteric artery aneurysm. A case report and
      review of the literature.
AB  - Superior mesenteric artery aneurysms are rare, comprising only 8% of all visceral
      artery aneurysms. Aneurysms at the site are very susceptible to rupture,
      irrespective of size and may be difficult to manage even in the case of elective
      surgery. In the absence of serious complicating factors, the treatment of choice
      is excision of the aneurysm and reconstruction of the artery, if necessary, to
      maintain patency. We report the successful resection of an aneurysm and the
      subsequent reconstruction of the superior mesenteric artery which was directly
      anastomosed to the aorta after resection of an aneurysm.

PMID- 10952345
TI  - Latex rubber (Penrose drain) is detrimental to esophagogastric anastomotic
      healing in rats.
AB  - BACKGROUND: Surgeons commonly drain cervical esophagogastric anastomoses, but
      there is little objective evidence to support this practice. Studies in other
      areas of gastrointestinal surgery have shown that routine drainage is
      unnecessary, and even detrimental to anastomotic healing. We conducted an animal
      experiment to see if a drain had a negative effect on esophagogastric anastomotic
      healing. METHODS: Esophagogastric anastomoses were done in 40 rats. In the
      experimental group (20 rats) a portion of latex rubber Penrose drain was placed
      over the anastomosis. This was not done in the control group (20 rats). Rats were
      sacrificed 7 days after surgery. The anastomoses were inspected for leaks,
      distracted in a tensiometer to measure breaking strength, and subjected to
      hydroxyproline analysis (an indicator of wound collagen). RESULTS: There were 4
      contained leaks in the experimental group (drain) and no leaks in the control
      rats (p=0.033). Anastomotic breaking strength was 3.80+/-0.81 N in the
      experimental rats and 3.46+/-0.64 N in the control rats (p=0.18, not
      significant). Anastomotic tissue hydroxyproline concentration was 615.9+/-52
      nmol/mg in the experimental rats and 609.4+/-195 nmol/mg in the control rats
      (p=0.13, not significant). CONCLUSIONS: The presence of drain material
      predisposed to esophagogastric anastomotic leakage in this rat model.

PMID- 10952346
TI  - Long-term results after pulmonary resection in elderly patients with non-small
      cell lung cancer.
AB  - BACKGROUND: The number of elder by patients with lung cancer is expected to
      increase. But, there was no report that 10 years completely passed in surgically
      treated elderly patients (E-pts). This study assesses late results of surgery.
      METHODS: From 1981 to 1987, 160 patients with non-small cell lung cancer
      underwent lobectomy or pneumonectomy with mediastinal lymph node dissection. Of
      these, 37 (23%) were 70 years of age or older. The outcome of this group was
      compared with that of 123 non-elderly patients (NE-pts). RESULTS: There were no
      significant differences in the background between E-pts and NE-pts. Five- and 10
      year survivals in the E-pts were 35.1%, and 24.3%, respectively. In outcome more
      than 5 years from operation, E-pts had a significantly poorer prognosis than NE
      pts (p=0.04) by any causes of death, but a similar prognosis by primary death. E
      pts died of nontumor-related death significantly more than NE-pts (p=0.6).
      CONCLUSIONS: This study showed that E-pts could consummate their lives
      completely. Additionally, when long-term prognosis of the postoperative E-pts was
      discussed, we should contemplate that E-pts had more deaths from nontumor-related
      causes.

PMID- 10952347
TI  - Short-course immunosuppression using FK506 for rat tracheal allografts.
AB  - BACKGROUND: A minimizing immunosuppression after a tracheal allotransplantation
      is desirable. METHODS: We examined the usefulness of a short-course of
      immunosuppression after tracheal allotransplantation in rat. Each transplant
      consisting of a 5-ring segment was heterotopically implanted into the omentum.
      Four animals underwent a syngeneic transplantation and thus served as controls
      (Group A). Thirty animals underwent an allogeneic transplantation and were
      randomly classified into 4 groups as follows: No immunosuppression (Group B,
      n=6), treatment with 0.5 mg/kg of Tacrolims (FK506) (Group C, n=8), 1.0 mg/kg of
      FK506 (Group D, n=8), and 1.5 mg/kg of FK506 (Group E, n=8). Different doses of
      FK506 were administered intramuscularly for only three consecutive days after
      heterotopic tracheal allotransplantation. The serum levels of FK506 were then
      investigated 3, 7, 14, 21, and 28 days after transplantation in groups C, D, and
      E. All rats were killed 28 days after transplantation and then the implanted
      tracheae were harvested, and evaluated histologically. RESULTS: All animals
      survived for the protocol period. The graft morphology of Group E was
      significantly better than that of groups B, C, and D regarding both macro- and
      microscopy, and also showed the same findings as that of Group A, except for low
      grade mononuclear cell infiltration. Only in Group E, the FK506 blood level was
      maintained at over 0.5 ng/ml, which is the lowest detectable limit in this assay,
      until 21 days after transplantation. CONCLUSIONS: We thus conclude that 1.5 mg/kg
      of FK506 which was administered for only three consecutive days after surgery may
      be used to maintain the morphology of tracheal allografts in rats for 28 days
      after transplantation.

PMID- 10952348
TI  - True pulmonary carcinosarcoma. A case report. Undifferentiated carcinoma and
      chondrosarcoma.
AB  - An unusual case of pulmonary carcinosarcoma with chondrosarcomatous stromal
      component is presented. The clinical and histopathologic features are reviewed
      with reference to relevant literature.

PMID- 10952349
TI  - Left internal thoracic artery harvesting in pleural symphyses under minimally
      invasive direct vision.
AB  - In minimally invasive direct coronary artery bypass grafting (MIDCAB), the
      internal thoracic artery (ITA) is harvested under a direct-vision or
      videothoracoscopic techniques. However, whatever the technique used, dense
      pleural adhesions hamper ITA harvesting. We describe the case of a patient who
      underwent MIDCAB 40 years after a pulmonary resection for tuberculosis. The
      parietal pleura adhered to the left lung so firmly that we could not enter the
      intrapleural cavity. Therefore, the ITA was harvested creating an extrapleural
      tunnel Although this approach resulted in more operating time and bleeding, an
      anastomosis between the ITA and left anterior descending coronary artery was
      performed successfully. We believe that MIDCAB can be carried out even in
      patients with dense pleural adhesions.

PMID- 10952350
TI  - Superior vena cava syndrome caused by invasive epidermoid carcinoma.
AB  - Lung cancer is the most frequent cause of superior vena cava (SVC) syndrome.
      Malignant SVC syndrome is generally considered a contraindication to curative
      resection, although palliative bypasses are done for symptoms that do not respond
      to medical therapy. However, a majority of patients with such advanced disease
      die of complications caused by the primary tumor rather than distant metastasis.
      We present the case of one patient with lung cancer invading the mediastinal
      structures. Combined resection and replacement of the SVC with a segment of
      Dacron vascular graft was performed. Postoperative survival time was 24 months.

PMID- 10952351
TI  - FDG-PET detection of primary lung cancer in a patient with an isolated cerebral
      metastasis.
AB  - Positron emission tomography (PET) is a new diagnostic technique. It is used to
      differentiate benign from malignant pulmonary nodules and to detect metastasis
      and lymph node involvement in primary lung cancer, but little has been published
      about its possible interest for detection of unknown primary tumors. We report
      the case of a man who underwent resection of a cerebral tumor. A histological
      diagnosis of cerebral metastasis from adenocarcinoma with a probable pulmonary
      origin was made. Preoperative staging (including thoracoabdominal CT-scan and
      bone scan) did not show any pathologic image, particularly in the thorax. A whole
      body FDG-PET-scan was then performed. An isolated (1.5 cm of diameter)
      hypermetabolic focus was discovered in the left upper lobe. Bronchoscopy was
      normal An upper left lobectomy confirmed the presence of the primary lung
      adenocarcinoma. In this particular case, FDG-PET proved to be a very useful
      diagnostic method. New indications are being developed for it.

PMID- 10952352
TI  - Congenital malformation of the lung.
AB  - Congenital malformations of the lung are rare and vary widely in their
      presentation and severity. However, frequently they present with dramatic
      symptoms resulting in the need for prompt diagnosis and treatment. Five patients
      with congenital lung malformations were treated in Karadeniz Technical University
      Farabi Medical School Pediatric Surgery Department between June 1992 and January
      1997. There were one girl and four boys. The mean age was 42 days (range 1 to 120
      days) and the mean weight was 3.9 kg (range 2.4 to 5.4 kg). The following cases
      were included; one pulmonary agenesis, two congenital lobar emphysema, one
      pulmonary sequestration, and one cystic adenomatoid malformation. Respiratory
      distress was the most common presenting symptom. The diagnosis was performed by
      chest X-ray with postero-anterior and lateral view and thoracic computed
      tomography (CT). Associated congenital anomalies were detected in one patient and
      the following anomalies were found; esophageal atresia, tracheo-esophageal
      fistula, short distal esophagus, and small intrathoracic stomach Posterolateral
      thoracotomy was used for all patients and complete surgical resection was
      performed in four patients. Corrective surgery was delayed in one patient in whom
      extended respiratory support was required and he died on the ninth day due to
      respiratory failure. In four patients prognosis was excellent. In this article,
      diagnosis and treatment of congenital lung malformations are discussed.

PMID- 10952353
TI  - Mitral valve repair vs replacement for mitral valve prolapse with severe mitral
      regurgitation.

PMID- 10952354
TI  - Management of isolated iliac artery aneurysms.

PMID- 10952355
TI  - Infrarenal aortic dissection into an abdominal aortic aneurysm.

PMID- 10952356
TI  - Tissue scar formation after transmyocardial laser revascularization.

PMID- 10952357
TI  - Age-dependent expression of fibrosis-related genes and collagen deposition in rat
      kidney cortex.
AB  - Because progressive fibrosis is a histological hallmark of the aging kidney, we
      sought to characterize the course of some fibrosis-related genes [pro
      alpha2(I)collagen (COL-I), pro-alpha1(III)collagen (COL-III), and transforming
      growth factors beta1 and beta3 (TGF-beta1 and TGF-beta3)] of interstitial
      collagen accumulation [COL-I and COL-III proteins, hydroxyproline (PRO-OH),
      histology] and its degradation (matrix metalloproteinase MMP-1 and -2) during
      maturation and early aging in rats. During the lifespan considered we observed no
      changes in the mRNA, except that COL-I mRNA tended to be up-regulated from 2 to
      19 months of age. However, progressive fibrosis was histologically detectable,
      with COL-I accumulation (p < .05 and p < .01 in 12-month- and 19-month-old rats
      vs the youngest), and confirmed by the PRO-OH tissue levels (p = .0001); COL-III
      seemed to be less involved. The MMP-1 protein level decreased significantly in
      the cortex of 12-month- and 19-month-old rats (p < .05), whereas MMP-2 protein
      level and activity remained essentially unchanged. These results show that,
      during aging of the kidney, (i) renal cortex fibrosis is explained by COL-I
      accumulation as a consequence of an altered balance between its synthesis and
      degradation, and (ii) the expression of the pleiotropic factor TGF-beta in the
      renal cortex is not modified.

PMID- 10952358
TI  - Locomotor activity in female rhesus monkeys: assessment of age and calorie
      restriction effects.
AB  - As a component of a long-term, longitudinal study of aging in this primate model,
      the objective of the current experiment was to assess age and diet effects on
      locomotor activity in a cross-sectional analysis. By attaching a motion detection
      device to the home cage, locomotor activity was monitored over a week in a group
      (N = 47) of female rhesus monkeys (Macaca mulatta) 6-26 yrs of age. About half
      these monkeys composed a control group fed a nutritionally fortified diet near ad
      libitum levels, whereas an experimental group had been fed the same diet at
      levels 30% less than comparable control levels for approximately 5 yrs prior to
      testing. Among control monkeys, a marked age-related decline in activity was
      noted when total activity was considered and also when diurnal and nocturnal
      periods of activity were analyzed separately. When comparing activity levels
      between control and experimental groups, only one significant diet effect was
      noted, which was in the youngest group of monkeys (6-8 yrs of age) during the
      diurnal period. Monkeys in the experimental group exhibited reduced activity
      compared to controls. Body weight was not consistently correlated to activity
      levels. In some older groups, heavier monkeys tended to show greater activity,
      but in younger groups the opposite pattern was observed.

PMID- 10952359
TI  - Why do life spans differ? Partitioning mean longevity differences in terms of age
      specific mortality parameters.
AB  - Populations typically differ in mean life spans because of genetic,
      environmental, or experimental factors. In this paper methods are presented that
      clarify the relationship between differences in the longevity of two populations
      and differences in their underlying age-specific patterns of mortality. Data are
      examined from rodent and fruit fly (Drosophila melanogaster) experiments that
      investigated the longevity effects of a variety of environmental and genetic
      manipulations, including temperature, dietary restriction, laboratory selection
      for increased longevity, and severe inbreeding. Analyses suggest that longevity
      differences mediated by temperature and dietary restriction result predominantly
      from differences in the rate of increase in mortality with age. Increases in
      longevity through laboratory selection result primarily from a reduction in
      baseline mortality and not a slowing of the rate of aging. Although the methods
      are applied primarily in the context of simple mathematical models of mortality
      (e.g., the Gompertz model), they are quite general and can be applied to
      mortality models of arbitrary complexity. Mathematica protocols ("notebooks") and
      computer software have been developed to perform all the analyses discussed and
      are available from the first author.

PMID- 10952360
TI  - Increased bioactivity of rat atrial extracts: relation to aging and blood
      pressure regulation.
AB  - The purpose of this study was to evaluate the possible role of atrial factor(s)
      in the regulation of cardiovascular homeostasis and their relationship to aging.
      Rats were anesthetized and received jugular vein, carotid artery, and bilateral
      ureteral catheterization. After a half-hour equilibration period, the rats
      received 0.5 ml of atrial extract with a concentration of proANP (atrial
      natriuretic peptide) of 150 microg/ml prepared from either aged (18-20 month,
      "aged extract group", n = 12) or young (2-3 month, "young extract group", n = 12)
      rats. Mean arterial pressure (MAP) and renal function were monitored over five 20
      minute periods. The atrial extract caused MAP to fall significantly in the aged
      extract group (p < .05) but MAP was unchanged in young extract group. There was a
      significant difference in MAP between the two groups (p < .05). Urine output
      increased significantly in both groups after extract infusion (p < .05 in both
      cases). Sodium and potassium excretion showed similar responses. However, the
      diuresis, natriuresis, and kaliuresis after extract infusion would have been
      expected to be relatively lower in the aged extract group compared to the young
      extract group considering the significantly lower MAP in the aged extract group.
      High performance gel permeation chromatography (HP-GPC) analysis of the atrial
      extract showed an increased quantity of a large molecular weight C-terminal
      peptide in atrial extracts from aged rats compared to young rat atria. Plasma
      levels of ANP and proANP 1-30 both increased significantly after extract infusion
      in both aged and young groups, and there was no significant difference in ANP
      concentration between the two groups. However, the concentration of proANP 1-30
      was significantly increased in the aged group compared to the young group after
      extract infusion. These results suggest that changes in the structure or
      processing of proANP in aging may contribute to the different hemodynamic
      responses.

PMID- 10952361
TI  - Effects of age and gender on rat upper airway muscle contractile properties.
AB  - Upper airway muscles regulate upper airway patency. Obstructive sleep apnea is
      caused by upper airway collapse, and its incidence increases with age and is
      higher in men than women. The reasons for this are unknown, as little is known
      about the effects of age and gender on upper airway muscle. Isometric contractile
      properties were determined using strips of geniohyoid and sternohyoid muscles
      from young and old, male and female rats in physiological saline solution at 30
      degrees C. There were no differences between the male and female rats in any of
      the contractile properties of either muscle, and this was true for both young and
      old animals. Aging had no effect on sternohyoid contractile properties, but
      geniohyoid force was greater in old than in young rats.

PMID- 10952362
TI  - Favorable neuromuscular and cardiovascular responses to 7 days of exercise with
      an eccentric overload in elderly women.
AB  - The metabolic, cardiovascular, and neural cost of eccentric muscle contraction is
      less than that of concentric contraction, but the strength and neural adaptations
      in eccentric contractions are significantly greater following resistive exercise.
      We thus compared the short-term effects of exercise with an eccentric overload (n
      = 10) with those of exercise with a standard load distribution (n = 10) in
      ostensibly healthy sedentary elderly women (mean age 71.4). Subjects were tested
      for concentric and eccentric three-repetition maximum, maximal isokinetic
      eccentric and concentric and isometric force, and associated electromyographic
      activity of selected thigh muscles before and after 7 consecutive days of
      exercise training of the left knee extensors. The exercise program was designed
      so that the total weight lifted was similar between eccentric overload and
      standard groups, but the eccentric overload group exercised with an approximately
      50% greater eccentric load. Control subjects did not exercise (n = 10). There was
      a 46% increase in the total weight lifted over 7 days. When all strength measures
      were combined, the eccentric overload group's strength gains were 1.8-fold
      greater than those of the standard group, and the cardiovascular stress in terms
      of heart rate, mean arterial pressure, rate pressure product, and perceived
      exertion was significantly lower. The increases in muscle strength were achieved
      by increased muscle activation, but the strength gains were independent of the
      changes in antagonistic muscle coactivity. Because the strength gains occurred
      after a short period of exercise at a relatively low intensity and cardiovascular
      demand, the prescription of exercise with an eccentric overload appears suitable
      for elders, individuals deconditioned as a result of an injury, and the
      chronically diseased.

PMID- 10952363
TI  - Systems contributing to balance disorders in older adults.

PMID- 10952364
TI  - A clinical measure of maximal and rapid stepping in older women.
AB  - BACKGROUND: In older adults, clinical measures have been used to assess fall risk
      based on the ability to maintain stance or to complete a functional task.
      However, in an impending fall situation, a stepping response is often used when
      strategies to maintain stance are inadequate. We examined how maximal and rapid
      stepping performance might differ among healthy young, healthy older, and balance
      impaired older adults, and how this stepping performance related to other
      measures of balance and fall risk. METHODS: Young (Y; n = 12; mean age, 21
      years), unimpaired older (UO; n = 12; mean age, 69 years), and balance-impaired
      older women IO; n = 10; mean age, 77 years) were tested in their ability to take
      a maximal step (Maximum Step Length or MSL) and in their ability to take rapid
      steps in three directions (front, side, and back), termed the Rapid Step Test
      (RST). Time to complete the RST and stepping errors occurring during the RST were
      noted. RESULTS: The IO group, compared with the Y and UO groups, demonstrated
      significantly poorer balance and higher fall risk, based on performance on tasks
      such as unipedal stance. Mean MSL was significantly higher (by 16%) in the Y than
      in the UO group and in the UO (by 30%) than in the IO group. Mean RST time was
      significantly faster in the Y group versus the UO group (by 24%) and in the UO
      group versus the IO group (by 15%). Mean RST errors tended to be higher in the UO
      than in the Y group, but were significantly higher only in the UO versus the IO
      group. Both MSL and RST time correlated strongly (0.5 to 0.8) with other measures
      of balance and fall risk including unipedal stance, tandem walk, leg strength,
      and the Activities-Specific Balance Confidence (ABC) scale. CONCLUSION: We found
      substantial declines in the ability of both unimpaired and balance-impaired older
      adults to step maximally and to step rapidly. Stepping performance is closely
      related to other measures of balance and fall risk and might be considered in
      future studies as a predictor of falls and fall-related injuries.

PMID- 10952365
TI  - Change in muscle mass and muscle strength after a hip fracture: relationship to
      mobility recovery.
AB  - BACKGROUND: Hip fracture in elderly persons has a serious impact on long-term
      physical function. This study determines the change in muscle strength and muscle
      mass after a hip fracture, and the associations between these changes and
      mobility recovery. METHODS: Ninety community-dwelling women aged 65 years and
      older who had recently experienced a fracture of the proximal femur were included
      in the study. At 2 to 10 days after hospital admission, the women's grip
      strength, ankle dorsiflexion strength, and regional muscle mass (by dual-energy x
      ray absorptiometry) were measured, and the prefracture level of independence for
      five mobility function items was assessed. All measurements were repeated at 12
      months. RESULTS: At follow-up, only 17.8% of the women had returned to their
      prefracture level of mobility function for all five items. Mobility function
      recovery was not related to change in skeletal muscle mass of the nonfractured
      leg or the arms. However, women who lost grip strength (mean loss of -28.7%, SD =
      16.9%), or who lost ankle strength of the nonfractured leg (mean loss of -21.5%,
      SD = 14.7%), had a worse mobility recovery compared with those who gained
      strength (p = .04 and p = .09, respectively). In addition, chronic disease (p =
      .03), days hospitalized (p = .04), and self-reported hip pain (p = .07) were
      independent predictors of decline in mobility function. CONCLUSIONS: The results
      suggest that loss of muscle strength, but not loss of muscle mass, is an
      independent predictor of poorer mobility recovery 12 months after a hip fracture.
      When confirmed by other studies, these findings may have implications for
      rehabilitation strategies after a hip fracture.

PMID- 10952366
TI  - Spinal flexibility and balance control among community-dwelling adults with and
      without Parkinson's disease.
AB  - BACKGROUND: One area of research that requires further elaboration is the
      relationship between impairments and functional limitations. By identifying
      specific contributors to functional limitations, it may be possible to establish
      intervention strategies, including exercise approaches, that can delay or
      ameliorate decline in function. The association between impaired spinal
      flexibility and functional limitations has not been studied in depth. The
      purposes of this study were to determine (a) the associations between spinal
      flexibility and functional limitations; (b) the relative contribution of spinal
      flexibility to specific functional limitations; and (c) how disease state
      (Parkinson's disease [PD] vs no PD) modified these relationships. METHODS:
      Participants included 251 community-dwelling adults, 56 of whom were with
      diagnosed PD and 195 were without PD or other specific disorders. Measures
      included spinal flexibility (i.e., functional axial rotation [FAR]) and
      configuration (i.e., thoracic kyphosis and lumbar lordosis), functional
      limitations (i.e., functional reach, supine-to-stand time, 10-m walk, and 360
      degrees turn). RESULTS: Canonical correlation (Can R) demonstrated significant
      associations between spinal measures and functional limitations (Can R = .488, p
      = .0001). After controlling for age, gender, race, body mass index, comorbidity,
      confidence, and depression, a multivariate regression model demonstrated that
      spinal flexibility contributed significantly to functional reach (R2 = .334 for
      the overall model, p = .0001). Based on the parameter estimate of 0.026, the
      results prediet that FAR accounts for a 4.6-inch difference in reach distance
      between the least and most flexible of the participants. In addition, there were
      significant differences between almost all measurements for the PD compared with
      the non-PD participants. CONCLUSION: Results clearly implicate spinal flexibility
      as a contributor to functional reach, a measure of functional limitation and an
      established measure of balance control. Further work is needed to determine the
      extent to which spinal flexibility can be improved and the effect of that
      improvement on balance.

PMID- 10952367
TI  - Genetic and environmental influences on functional abilities in Danish twins aged
      75 years and older.
AB  - BACKGROUND: Functional abilities vary widely among elderly persons. The
      determinants of this variation are probably multiple and include normal aging
      processes as well as disease expression. This study estimates the relative
      importance of genetic and environmental factors to variation in functional
      abilities in elderly persons. METHODS: We conducted a survey among all Danish
      twins aged 75 years and older who were identified in the population-based Danish
      Twin Registry. Interviews were conducted with 77% (7% by proxy responders) of the
      3099 individuals in the study population. Functional abilities were assessed by
      validated Danish survey instruments and were scored on three scales. Heritability
      (proportion of the population variance attributable to genetic variation) was
      estimated using structural equation analyses. RESULTS: Structural equation
      analyses revealed a substantial heritability (34%-47%) for the three functional
      ability scores among the women aged 80 years and older compared with a more
      modest heritability (15%-34%) among the women aged 75-79 years. The remaining
      variation could be attributed to individuals' nonfamilial environments.
      Comparisons of the functional abilities of twins with living versus deceased co
      twins also suggested a difference in the genetic influence for the two age
      groups. Although heritability estimates were uniformly low in the male
      participant sample, the size of the sample was not sufficiently large to allow
      for precise estimates of heritability. CONCLUSION: For women we found that the
      effect of genetic factors on functional abilities increases with age and accounts
      for one third to one half of the variation among individuals aged 80 years and
      older. An understanding of the genetic mechanisms underlying functional abilities
      in the oldest individuals may enhance the possibilities for improving health in
      the elderly population by modifying environmental factors.

PMID- 10952368
TI  - Weight loss, not aerobic exercise, improves pulmonary function in older obese
      men.
AB  - BACKGROUND: We evaluated the effect of weight loss (WL) or aerobic exercise (AEX)
      on pulmonary function in middle-aged and older (46-80 years) obese, sedentary men
      to determine the effect of reductions in body weight and increases in
      cardiorespiratory fitness on pulmonary function. METHODS: Subjects were randomly
      assigned to WL (n = 73), AEX (n = 71), or control (n = 26) groups. Maximal oxygen
      uptake (VO2max), body composition and anthropometrics, pulmonary function, and
      arterial blood gases were measured at baseline and after interventions. RESULTS:
      The 35 subjects who completed WL decreased weight by 11%, body fat percentage by
      21% (p < .001), waist circumference by 8%, waist-hip ratio by 2%, and fat-free
      mass by 3% (p < .05). This resulted in a 3% increase in forced vital capacity
      (FVC) (4.08 +/- 0.71 L vs 4.21 +/- 0.76 L), a 5% increase in total lung capacity
      (6.62 +/- 0.99 L vs 6.94 +/- 0.99 L), an 18% increase in functional residual
      capacity (3.09 +/- 0.58 L vs 3.66 +/- 0.79 L), and an 8% increase in residual
      volume (2.20 +/- 0.44 L vs 2.37 +/- 0.52 L), with no change in forced expiratory
      volume in one second (FEV1), FEV1/FVC ratio, or carbon monoxide diffusing
      capacity. The change in FVC correlated with change in body weight (r = -.34, p <
      .05). The 38 subjects who completed AEX increased VO2max by 14%, with no change
      in pulmonary function. There were no changes in 8 control subjects. CONCLUSIONS:
      WL changes static lung volumes, not dynamic pulmonary function, in middle-aged
      and older, moderately obese, sedentary men. Some of the alterations in static
      lung function associated with aging may be due to the development of obesity and
      are modifiable by WL.

PMID- 10952369
TI  - Diagnostic yield and development of a neurocardiovascular investigation unit for
      older adults in a district hospital.
AB  - BACKGROUND: Dizziness, syncope, and falls are common occurrences in elderly
      people. Neurocardiovascular investigation units aim to detect those patients who
      fall due to disturbances of blood pressure control or cardiac conduction.
      Specialist units have a high diagnostic yield in the investigation of these
      problems. Does this translate to less specialized centers? We report on the
      diagnostic findings of a district general hospital neurocardiovascular
      investigation unit. METHOD: A total of 120 consecutive patients over the age of
      65 presenting to a single geriatrician were assessed. After a full history and
      physical examination, patients underwent neurocardiovascular investigation: blood
      pressure and heart rate response to active stand, carotid sinus massage, and 30
      minute head-up tilt. RESULTS: The 120 patients assessed had a mean age of 78
      years (range 66-94 years); in this group, 85 were women. Of these patients, 23%
      presented with falls, 14% with blackouts, and 30% with dizziness. The remaining
      33% had overlap of symptoms. Neurocardiovascular investigations produced a
      diagnosis in 57% of the patients: 22% had cardioinhibitory carotid sinus syndrome
      (CSS): 15% had vasodepressor CSS; 29% had orthostatic hypotension; and 3% had
      vasovagal syncope. Thirteen percent had more than one neurocardiovascular
      abnormality, and 18% had benign positional vertigo. Five patients had postural
      instability causing falls. Hyperventilation syndrome, aortic stenosis,
      dysrhythmia, cervical spondylosis, and epilepsy each accounted for one case.
      Seventeen percent of the subjects remained undiagnosed after integrated
      neurocardiovascular assessment. CONCLUSION: Management of falls requires access
      to neurocardiovascular assessment. It is feasible to provide such a service in
      the district general hospital setting, with a comparable diagnostic yield to
      tertiary referral centers.

PMID- 10952370
TI  - Hypertension in elderly persons: its prevalence and associated cardiovascular
      risk factors in Tainan City, southern Taiwan.
AB  - BACKGROUND: Hypertension was the eighth leading cause of death in Taiwan in 1996,
      and the prevalence of hypertension has increased recently. The purpose of the
      study was to assess the prevalence of hypertension and its associated
      cardiovascular risk factors in elderly persons in Tainan City, southern Taiwan.
      METHODS: The study was a cross-sectional, population-based study. We used the
      stratified cluster sampling method to enroll subjects aged 65 years and above,
      1435 persons in total, into our study. Questionnaire interview, body weight, body
      height, and blood pressure measurement were completed for 876 participants
      (response rate of 70.2%) at each subject's home by home visit. RESULTS:
      Hypertension was defined according to the criteria of the Fifth Report of the
      Joint National Committee on Detection, Evaluation, and Treatment of High Blood
      Pressure. The crude prevalence of hypertension was 60.4% (men 59.1%, women
      61.9%); previously diagnosed hypertension was 31.1% (men 29.4%, women 33.1%); and
      newly diagnosed hypertension was 29.3% (men 29.7%, women 28.8%). The hypertensive
      group had a higher body mass index (BMI) than the normotensive group. There were
      no lifestyle differences such as smoking, drinking, eating a vegetarian diet,
      reading health information, and undergoing a health examination in the past year
      between the hypertensive and normotensive groups. However, the hypertensive group
      had a higher prevalence of regular exercise than did the normal blood pressure
      group on univariate analysis. Only BMI and family history of hypertension had a
      significantly positive association with hypertension on multiple logistic
      regression analysis. CONCLUSIONS: The crude prevalence of hypertension was 60.4%
      in elderly persons in Tainan City. Subjects who had family history of
      hypertension and higher BMI had a higher risk of hypertension, so they should be
      screened for high blood pressure regularly.

PMID- 10952371
TI  - A prospective study of laboratory and clinical measures of postural stability to
      predict community-dwelling fallers.
AB  - BACKGROUND: The identification of specific risk factors for falls in community
      dwelling elderly persons is required to detect early changes and permit a
      preventative approach to management. This study determines the ability of various
      laboratory measures and clinical tests of postural stability to prospectively
      predict fallers in community-dwelling elderly women. METHODS: One hundred elderly
      women (65-86 years, mean age 73 +/- 5 years) performed a reaction-time step task,
      a limits of stability, and a quiet stance balance task. Postural muscle timing
      and movement speed were recorded during the step task. Center of pressure (COP)
      motion was recorded in quiet stance and at the limits of stability. Four common
      clinical balance tests were performed, and balance confidence, medical and
      activity history questionnaires were completed. Subjects were followed up
      regularly for a 6-month period following testing to determine the frequency and
      characteristics of any falls that occurred. Predictive capabilities of the
      balance measures to determine fallers were determined through logistic regression
      models. RESULTS: The clinical balance tests investigated were not able to predict
      fallers in this community-dwelling elderly population. A combination of variables
      from the laboratory tasks provided the best overall prediction rate (77%) of
      fallers (sensitivity 51%) and nonfallers (specificity 91%) from laboratory
      measures. Of these, step movement time and gluteus medius onset times were the
      factors best able to predict fallers. Alone, measures of COP motion in quiet
      stance and at the limits of stability had a poor ability to predict fallers,
      although they could correctly identify most nonfallers. Prediction was not
      significantly improved when clinical balance test results were added to the most
      predictive laboratory measures. CONCLUSIONS: Not all older adults with a
      reduction in balance ability reported a fall over a 6-month period. Of those who
      did, a combination of measures reflective of different aspects of mediolateral
      postural stability during a rapid step task, quiet stance, and movement to the
      limits of stability were best able to predict faller status, with nonfallers
      better predicted than fallers. These results emphasize the importance of the
      multifactorial nature of falls in the community-dwelling elderly population in
      that the clinical and laboratory measures did not predict a high proportion of
      fallers.

PMID- 10952372
TI  - Autonomic and neurohumoral control of postprandial blood pressure in healthy
      aging.
AB  - BACKGROUND: Postprandial hypotension (PPH) is a common and morbid problem in
      elderly people that is associated with an impaired vascular response to meal
      digestion. Healthy aging in the absence of blood pressure elevation is associated
      with autonomic and neurohumoral changes that may influence the vascular response
      to meal ingestion. However, it is not known whether these age-related changes are
      associated with the development of PPH. METHODS: We measured hemodynamic (blood
      pressure, heart rate, and forearm vascular resistance), autonomic (power spectral
      analysis of heart rate and blood pressure variability), and neurohumoral (plasma
      norepinephrine, renin, aldosterone, and endothelin) responses to a mixed 425
      kilocalorie (kcal) meal in 89 rigorously screened healthy subjects aged 20-39, 40
      59, and 60-83 years. RESULTS: After the meal, supine mean arterial blood pressure
      fell significantly only in the middle-aged group by 5.4 +/- 7.9 mm Hg at 30
      minutes (p = .02). Forearm vascular resistance fell after the meal in all age
      groups ( p = .0001). Older groups had higher plasma norepinephrine (p = .02),
      lower heart rate (p = .03), lower cardiovagal activity (p = .0001), and lower
      sympathetic vasomotor (p = .000) activity, but there was no difference in the
      response of these variables to a meal. CONCLUSION: Healthy aging, in the absence
      of blood pressure elevation, alters the level of autonomic activity without
      further impairing the ability to maintain blood pressure during meal digestion.
      Hemodynamic, autonomic, and neurohumoral responses to meal ingestion remain
      unchanged in very healthy, normotensive elderly adults.

PMID- 10952373
TI  - Bugs, snails and horses: expanding the knowledge of infection vectors with new
      and old technologies.

PMID- 10952374
TI  - Transmission of Ehrlichia risticii, the agent of Potomac horse fever, using
      naturally infected aquatic insects and helminth vectors: preliminary report.
AB  - Ehrlichia risticii, the agent of Potomac horse fever (PHF), has been recently
      detected in trematode stages found in snail secretions and in aquatic insects.
      Based on these findings, horses could conceivably be exposed to E. risticii by
      skin penetration with infected cercariae, by ingestion of infected cercariae in
      water or via metacercariae in a second intermediate host, such as an aquatic
      insect. In order to test this hypothesis, horses were challenged with infectious
      snail secretions and aquatic insects collected from a PHF endemic region in
      northern California. Two horses stood with their front feet in water harbouring
      E. risticii-infected cercariae, 2 horses drank water harbouring E. risticii
      infected cercariae, and 6 horses were fed pools of different aquatic insects
      harbouring E. risticii-infected metacercariae. In this preliminary study, only
      the one horse infected orally with mature caddisflies (Dicosmoecus gilvipes)
      developed the clinical and haematological disease syndrome of PHF. The agent was
      isolated from the blood of the infected horse in a continuous cell line and
      identified as E. risticii by characterisation of the 16S rRNA gene. Therefore, E.
      risticii is maintained in nature in a complex aquatic ecosystem and transmission
      to horses can occur through accidental ingestion of insects such as caddisflies
      containing infected metacercariae. At present, the small number of horses used in
      this study does not exclude other insects and free trematode stages as potential
      sources of infection.

PMID- 10952375
TI  - Pleuropulmonary and cardiovascular consequences of thoracoscopy performed in
      healthy standing horses.
AB  - Six healthy, awake, and pharmacologically restrained mature horses were studied
      in order to define the changes in cardiopulmonary function during and after
      exploratory thoracoscopy and to determine the presence of postoperative
      complications occurring 48 hours after thoracoscopy. In a randomised 3 x 3 latin
      square design with 2 replications, 18 procedures were performed: 6 right (RTH)
      and 6 left thoracoscopies (LTH) and 6 sham procedures (STH). Prior to each
      procedure a physical examination and a bronchoalveolar lavage fluid analysis were
      performed. During thoracoscopy and sham protocols, horses were sedated with a
      continual drip of detomidine HCl and data were collected at 6 time intervals: T1
      (baseline), T2 (10 min detomidine administration), T3 (first 15 min
      pneumothorax), T4 (5 min recovery from pneumothorax), T5 (second 15 min
      pneumothorax), and T6 (10 min recovery from the second pneumothorax and
      detomidine). An endoscopic thoracic examination was conducted during the 2
      pneumothorax periods. An identical protocol was followed for sham procedures
      without surgery or pneumothorax. Data were analysed by ANOVA with time and
      surgical procedure as main factors. Physical examinations, thoracic radiography
      and ultrasound, CBC and bronchoalveolar lavage fluid analysis were performed 48 h
      after thoracoscopy. Heart rate, respiratory rate, and cardiac output decreased
      following detomidine administration. There was a trend for cardiac output to be
      lower during thoracoscopy. Mild systemic hypertension was associated with
      thoracoscopy although there was no effect on pulmonary arterial pressure. Total
      and pulmonary vascular resistances were increased following detomidine
      administration. Thoracoscopy caused a further increase in systemic and pulmonary
      vascular resistances especially during the second pneumothorax. Arterial O2
      tension decreased following detomidine administration and was further decreased
      during the second pneumothorax period. PaO2 values were lower when thoracoscopy
      was performed on the left rather than the right hemithorax. No significant
      complications were found during the 48 h follow-up evaluation. A subclinical
      postoperative pneumothorax occurred in 2 horses, one of which had sustained a
      lung laceration by the trocar. Thoracoscopy performed in healthy, awake, and
      pharmacologically restrained horses did not have detrimental cardiopulmonary
      effects and did not cause postoperative complications within the first 48 h
      period.

PMID- 10952376
TI  - The forelimb in walking horses: 1. Kinematics and ground reaction forces.
AB  - Video (60 Hz) and force (2000 Hz) data were collected from 5 sound horses during
      walking. Forelimb data were analysed for 8 strides (4 left, 4 right) per horse to
      determine sagittal plane kinematics and ground reaction forces (GRFs). The
      results suggested that brachial rotation was responsible for protraction and
      retraction of the limb as a whole, while rotations of the scapula and
      antebrachium elevated the distal limb during breakover and early swing then
      lowered it in preparation for ground contact. The coffin joint was flexed
      maximally at the time of peak longitudinal braking force, which occurred during
      breakover of the contralateral forelimb. The metacarpus was vertical at 28%
      stride. This was considerably earlier than the change from a braking to a
      propulsive longitudinal force (34% stride), which coincided with maximal
      extension of the fetlock joint. The longitudinal propulsive force peaked just
      after contact of the contralateral forelimb. During the swing phase the joints
      distal to the shoulder showed a single flexion cycle that peaked at 76% stride at
      the carpus, 81% stride at the fetlock and 84% stride at the elbow and coffin
      joints. The coffin and shoulder joints began to extend in the terminal swing
      phase and continued to extend through ground contact and early stance. The
      results provide normative data that will be applied in detecting changes in
      kinematics and ground reaction forces that are associated with specific
      lamenesses.

PMID- 10952377
TI  - The forelimb in walking horses: 2. Net joint moments and joint powers.
AB  - The objective was to measure the net joint moments and joint powers for the
      joints of the equine forelimb during the walk. Videographic and force data were
      combined with morphometric information using an inverse dynamics method. During
      stance phase the predominant joint moment was on the palmar aspect of all
      forelimb joints except the shoulder, where the peak moment was considerably
      higher than at any other joint. The entire forelimb showed net energy absorption
      in both stance and swing phases. The elbow was the only joint that showed net
      generation of energy, which was used to maintain the limb in extension in early
      stance as the horse's body vaults over the limb and to drive protraction and
      retraction of the limb during swing. The carpus aligned the limb into a
      supportive strut, but did not play an important role in energy absorption or
      generation. A small burst of positive work on the flexor aspect at the start of
      breakover indicated that the carpus played an active role in initiating breakover
      during walking. The fetlock functioned elastically to store and release strain
      energy during stance. The coffin joint acted as an energy damper during most of
      stance with a small burst of energy generation on the flexor aspect as the joint
      flexed during breakover. The magnitude of the peak joint power during swing
      decreased in a proximal to distal sequence. It is concluded that the elbow joint
      is the main site of energy generation. The shoulder and coffin joints act as
      energy dampers during stance. The distal joints had very low joint powers and
      appeared to be driven by inertial forces during the swing phase. This information
      will be applied to describe how horses compensate for different lamenesses in
      terms of redistributing the functions of energy generation and absorption between
      joints.

PMID- 10952378
TI  - Medical treatment of cholangiohepatitis and cholelithiasis in mature horses: 9
      cases (1991-1998).
AB  - The medical approach to treatment of cholangiohepatitis and cholelithiasis in 9
      horses is described. Seven horses were treated successfully and returned to
      normal use, with a minimum follow-up period of 12 months. Long-term antimicrobial
      therapy was believed to be critical in those cases that survived, with a median
      treatment duration of 51 days (range 17-124 days). Treatment failure was
      associated with severe periportal and bridging hepatic fibrosis from biopsy
      material obtained at admission in 2 horses, one of whom also presented with
      hyperammonaemic hepatic encephalopathy. Transabdominal ultrasound was used
      diagnostically in each case to obtain hepatic biopsy material for histopathology
      and bacterial culture, to evaluate hepatic size and echogenicity and to identify
      and monitor the dissolution of hepatoliths. Histologically, all horses had
      evidence of suppurative cholangiohepatitis with varying degrees of periportal and
      bridging fibrosis. Discrete hyperechoic calculi were identified in 4 cases, but
      all horses had ultrasonographic evidence of biliary obstruction with numerous
      dilated bile ducts. Aerobic and anaerobic cultures of liver biopsy material were
      negative from 7 horses, but 2 different species of Escherichia coli were obtained
      from one horse, and Bacteroides vulgatus and Escherichia coli were isolated from
      another. In all 7 horses that survived, clinical recovery was seen before
      normalisation of biochemical indices of hepatobiliary function including
      gammaglutamyl transaminopeptidase (GGT), alkaline phosphatase (AP), bile acids
      and serum bilirubin. Serum GGT levels were monitored extensively as a marker of
      hepatobiliary disease and actually increased during the initial period of
      clinical improvement in horses that recovered. Supportive medical therapy with
      i.v. fluids was also a critical part of the therapy of several cases in this
      report, both acutely and in the management of chronic cases that deteriorated
      clinically during treatment. Previous therapeutic failures may well be related to
      treatment periods of inadequate duration, and the authors recommend that
      antimicrobial therapy should be continued until GGT values are normal.

PMID- 10952379
TI  - Clinical studies on daily low dose oxytocin in mares at term.
AB  - The aim of this study was to test whether low dose oxytocin i.v. injection once a
      day to mares diagnosed as being ready for birth by mammary secretion calcium
      strip test measurements could be used as a reliable method to induce parturition
      and/or predict the mare would not foal during the following night if parturition
      did not occur within 2 h of treatment. Fifty-one near-term Haflinger mares were
      used and a single injection of 2.5 iu oxytocin was given between 1700 and 1900 h,
      including 10 mares used as controls which were administered a placebo.
      Administration of oxytocin resulted in the delivery of a normal foal within 120
      min in 95% of mares. Twenty-four out of 38 (63%) treated animals foaled in
      response to the first oxytocin injection, 9 out of 38 (24%) in response to the
      second injection and 3 out of 38 (8%) in response to the third treatment. Two out
      of 38 (5%) treated mares foaled during the night irrespective of treatment
      whereas 7 out of 10 (70%) control mares foaled during the night. It was concluded
      that the major advantage of injecting a daily low dose of oxytocin appears to be
      that such a low dose induces delivery only in mares carrying a mature fetus and
      which are ready to foal.

PMID- 10952380
TI  - The effects of treadmill inclination and speed on the activity of two hindlimb
      muscles in the trotting horse.
AB  - Electromyographic activity (EMG) was used to determine how hindlimb muscle
      activation patterns vary with speed and incline in the horse. EMG was recorded
      using surface electrodes over the gluteus medius and tensor fasciae latae muscles
      during treadmill locomotion at trot for different combinations of speed (3.5 to 6
      m/s) and inclination (0, 3 and 6%). Raw EMG signals were processed to determine
      stride duration, activity onset and end, and integrated EMG (IEMG). Stride and
      stance phase duration decreased linearly with increasing speed. Stride duration
      was not influenced by the slope. Onset and end of muscle activity came
      significantly earlier in the stride cycle when speed increased and later when
      inclination changed from 0 to 6%. The relative duration of the burst (percentage
      of stride duration) increased as running speed increased, but tended to decrease
      with increasing slope. The IEMG of the muscles increased with increasing speed
      and slope, the largest increase being observed in the tensorfasciae latae. It is
      concluded that both increases in speed and inclination lead to an increase in the
      integrated electromyographic activity and hence to a higher workload of the 2
      hindlimb muscles investigated.

PMID- 10952381
TI  - A comparison of the haemodynamic effects of isoflurane and halothane anaesthesia
      in horses.
AB  - The purpose of this study was to compare the haemodynamic effects of equipotent
      isoflurane and halothane anaesthesia. Six adult horses were investigated on two
      separate occasions at least 4 weeks apart. On both occasions anaesthesia was
      induced by ketamine 2.2 mg/kg bwt given 5 min after i.v. administration 100
      microg/kg bwt romifidine. Anaesthesia was maintained either by halothane or
      isoflurane (end-tidal concentrations 0.9-1.0% and 1.3-1.4%, respectively). Horses
      were ventilated by intermittent positive pressure to maintain PaCO2 between 40-50
      mmHg. Haemodynamic variables were measured using catheter-mounted strain gauge
      transducers in the left and right ventricle, aorta, and right atrium. Cardiac
      output (CO), velocity time integral (VTI), maximal aortic blood flow velocity
      (Vmax) and acceleration (dv/dt(max)), left ventricular pre-ejection period (PEP)
      and ejection time (ET) were measured from aortic blood flow velocity waveforms
      obtained by transoesophageal Doppler echocardiography. Flow velocity waveforms
      were recorded from the femoral arteries and veins using low pulse repetition
      frequency Doppler ultrasound. Time-averaged mean velocity (TAV), velocity of
      component a (TaVa), velocity of component b (TaVb) and early diastolic
      deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric
      flow were calculated. Microvascular blood flow was measured in the left and right
      semimembranosus muscles by laser Doppler flowmetry. Maximal rate of rise of LV
      pressure (LVdp/dt(max)), CO, Vmax, dv/dt(max), ET, VTI were significantly higher
      at all time points during isoflurane anaesthesia compared to halothane
      anaesthesia. Pre-ejection period and diastolic aortic blood pressure were
      significantly less throughout isoflurane anaesthesia compared to halothane.
      Isoflurane anaesthesia was associated with significantly lower systemic vascular
      resistance than halothane anaesthesia. Femoral arterial and venous blood flow
      were significantly higher and EDDS and PI were significantly lower during
      isoflurane anaesthesia compared to halothane anaesthesia. In addition during both
      halothane and isoflurane anaesthesia, femoral arterial flow was higher and EDDS
      and PI lower in the left (dependent) artery compared to the right (nondependent)
      artery. This study supports previous work demonstrating improved left ventricular
      systolic function during isoflurane compared to halothane anaesthesia. This
      improvement was still evident after premedication with a potent-long acting
      alpha2-adrenoreceptor agonist, romifidine, and induction of anaesthesia with
      ketamine. There was also evidence of increased hindlimb blood flow during
      isoflurane anaesthesia. However, there were differences observed in flow between
      the left and right hindlimb during maintenance of anaesthesia with each agent,
      suggesting that there were differences in regional perfusion in anaesthetised
      horses caused by factors unrelated to agents administered.

PMID- 10952382
TI  - Cytotoxicity of stimulated equine neutrophils on equine endothelial cells in
      culture.
AB  - We studied the interactions of isolated equine neutrophils with endothelial cells
      in culture, mimicking a situation of acute inflammation. Our main purpose was to
      demonstrate that the supernatant of activated neutrophils was sufficient to
      damage endothelial cells. Equine endothelial cells (from carotid arteries) were
      covered either with increased numbers of equine neutrophils stimulated by phorbol
      myristate acetate, or with the supernatant collected after an in vitro
      stimulation of the neutrophils. Cytotoxicity was estimated by the release of
      preincorporated 51Cr, and by light microscopy observations. To assert the
      specific role of reactive oxygen species, endothelial cells were treated by the
      hypoxanthine/xanthine oxidase (X/XOx) system (production of superoxide anion and
      hydrogen peroxide), and by hypochlorite (product of the activity of
      myeloperoxidase). A strong cytotoxicity was found with stimulated neutrophils;
      microscopic observations indicated a loss of 50% of the endothelial cells and
      morphological alterations in the remaining cells. The supernatant of stimulated
      neutrophils was cytotoxic, in correlation with the number of neutrophils used to
      obtain the supernatant, and with the supernatant concentration of
      myeloperoxidase. The cytotoxicity of the X/XOx system was weak, but was increased
      by myeloperoxidase. Hypochlorite was highly toxic. We concluded that the
      supernatant of stimulated neutrophils was sufficient to obtain cytotoxic effects
      on the endothelium, in the absence of a direct contact between endothelium and
      neutrophils, and that this cytotoxicity was mainly linked to the activity of
      myeloperoxidase. From these in vitro results, it can be extrapolated that in
      pathologies characterised by an important activation of neutrophils, damage can
      spread to cells and tissues away from the inflammation focus.

PMID- 10952383
TI  - The effects of frusemide on racing times of Standardbred pacers.
AB  - Seven hundred and eighty-eight Standardbred pacers competing in 8378 races at one
      racetrack were analysed to determine the effects of the administration of prerace
      frusemide on racing times (RT). Frusemide was administered i.v. 4 h before the
      race to pacers diagnosed with exercise-induced pulmonary haemorrhage (EIPH). Of
      the pacers, starting in the 1997 racing season, 32.5% received prerace frusemide.
      This study demonstrated that administration of frusemide prior to racing
      significantly decreased RT. There was an overall significant decrease (P<0.00001)
      in RT of 0.67 s. The overall RT for horses, geldings, and females, were mean +/-
      s.e 117.91 +/- 0.06, 118.20 +/- 0.03 and 118.86 +/- 0.04, respectively. RT
      progressively decreased until age 6 and increased thereafter. Horses, geldings
      and females ran a mean of 0.46, 0.31 and 0.74 s faster, respectively, with
      prerace administration of frusemide. This decrease in RT following prerace
      administration was most pronounced in younger pacers. In this study, a greater
      percentage of older pacers received prerace frusemide; however, the effect of
      frusemide on RT was decreasing with age. Prerace venous acid-base screening was
      performed in 2729 of the pacers competing. Pennsylvania Harness Racing Commission
      Regulations disqualify Standardbreds from racing with a base excess of over 10
      and 12 mmol/l for Standardbreds without and with prerace administration of
      frusemide. The prerace venous acid-base levels were not significantly related to
      RT and, for those Standardbreds also sampled following the race, there was no
      correlation between pre- and postrace acid-base status.

PMID- 10952384
TI  - Effect of water restriction on equine behaviour and physiology.
AB  - Six pregnant mares were used to determine what level of water restriction causes
      physiological and/or behavioural changes indicative of stress. Nonlegume hay was
      fed ad libitum. During the first week of restriction, 5 l water/100 kg bwt was
      available, during the second week 4 l/100 kg bwt and, during the third week, 3
      l/100 kg bwt. Ad libitum water intake was 6.9 l/100 kg bwt; at 3 l/100 kg bwt
      water intake was 42% of this. Daily hay intake fell significantly with increasing
      water restriction from 12.9 +/- 0.75 kg to 8.3 +/- 0.54 kg; bodyweight fell
      significantly for a total loss of 48.5 +/- 8.3 kg in 3 weeks. Daily blood samples
      were analysed; osmolality rose significantly with increasing water restriction
      from 282 +/- 0.7 mosmols/kg to 293.3 +/- 0.8 mosmols/kg bwt, but plasma protein
      and PCV did not change significantly. Cortisol concentrations fell from 8.1 ng/ml
      to 6.4 ng/ml over the 3 week period. Aldosterone fell from 211.3 +/- 74.2 pg/ml
      to 92.5 +/- 27.5 pg/ml at the end of the first week. The behaviour of 4 of the 6
      mares was recorded 24 h/day for the duration of the study. The only significant
      difference was in time spent eating, which decreased with increasing water
      restriction from 46 +/- 3% to 30 +/- 3%. It is concluded that water restriction
      to 4 l/100 kg bwt dehydrates pregnant mares and may diminish their welfare, but
      is not life- or pregnancy-threatening.

PMID- 10952385
TI  - Influence of bacitracin on microbial functions in the gastrointestinal tract of
      horses.
AB  - This study investigated the influence of zinc bacitracin on the intestinal flora
      of horses. The functionally active intestinal flora was examined in 6 horses
      during treatment with zinc bacitracin. Utilising gas chromatography,
      spectrophotometry, gel electrophoresis and paper chromatography, samples were
      analysed on biochemical markers reflecting the action of parts of the intestinal
      flora. The following 5 flora-related functions were studied in faecal samples and
      intestinal samples from different sections of the hindgut: conversion of
      cholesterol to coprostanol and of bilirubin to urobilinogens, degradation of
      mucin and of beta-aspartylglycine and inactivation of tryptic activity.
      Conversion to coprostanol, conversion to urobilinogens and degradation of mucin
      were affected by treatment of zinc bacitracin and conversion to coprostanol was
      most sensitive. All functions were normalised in a short time, in contrast to man
      and rats. Differences in environmental exposures are probably the reason for a
      more rapid normalisation of the intestinal flora functions in horses.

PMID- 10952386
TI  - Rare intestinal malformation (diverticulum confluens) in a horse.

PMID- 10952387
TI  - Aortitis in a Paint gelding.

PMID- 10952388
TI  - Two sterile stallions with XXY-syndrome.

PMID- 10952389
TI  - Assembly, target-signaling and intracellular transport of tyrosinase gene family
      proteins in the initial stage of melanosome biogenesis.
AB  - Assembly, target-signaling and transport of tyrosinase gene family proteins at
      the initial stage of melanosome biogenesis are reviewed based on our own
      discoveries. Melanosome biogenesis involves four stages of maturation with
      distinct morphological and biochemical characteristics that reflect distinct
      processes of the biosynthesis of structural and enzymatic proteins, subsequent
      structural organization and melanin deposition occurring in these particular
      cellular compartments. The melanosomes share many common biological properties
      with the lysosomes. The stage I melanosomes appear to be linked to the late
      endosomes. Most of melanosomal proteins are glycoproteins that should be folded
      or assembled correctly in the ER through interaction with calnexin, a chaperone
      associated with melanogenesis. These melanosomal glycoproteins are then
      accumulated in the trans Golgi network (TGN) and transported to the melanosomal
      compartment. During the formation of transport vesicles, coat proteins assemble
      on the cytoplasmic face of TGN to select their cargos by interacting directly or
      indirectly with melanosomal glycoproteins to be transported. Adapter protein-3
      (AP-3) is important for intracellular transport of tyrosinase gene family
      proteins from TGN to melanosomes. Tyrosinase gene family proteins possess a di
      leucine motif in their cytoplasmic tail, to which AP-3 appears to bind. Thus, the
      initial cascade of melanosome biogenesis is regulated by several factors
      including: 1) glycosylation of tyrosinase gene family proteins and their correct
      folding and assembly within ER and Golgi, and 2) supply of specific signals
      necessary for intracellular transport of these glycoproteins by vesicles from
      Golgi to melanosomes.

PMID- 10952391
TI  - Making sense of melanosome dynamics in mouse melanocytes.
AB  - Molecular motors drive most if not all organelle movements in Eukaryotic cells.
      These proteins are thought to bind to the organelle surface and, through the
      action of their mechanochemical domains, to translocate the organelle along a
      cytoskeletal track. In the case of the myosin family of molecular motors, the
      cytoskeletal track is filamentous actin. Microtubules serve as the cytoskeletal
      track for the kinesins and dyneins. While a considerable amount is known about
      the motors and tracks responsible for the bi-directional movement of pigment
      granules in fish and frog melanophores, relatively little is known about how
      melanosomes in mammalian melanocytes are transported out the cells dendritic
      arbor, accumulated at the ends of these dendrites, and transferred to
      keratinocytes. In this short review, we focus on the use of video microscopy to
      address these questions in mouse melanocytes, and we describe how an analysis of
      melanosome dynamics within wild type and dilute melanocytes shaped our thinking
      regarding the role of an unconventional myosin in melanosome transport and
      distribution.

PMID- 10952390
TI  - MITF: a stream flowing for pigment cells.
AB  - Microphthalmia-associated transcription factor (MITF) is a transcription factor
      with a basic-helix-loop-helix-leucine zipper (bHLHZip) structure. Mutations of
      the MITF gene cause a variety of phenotypes, most notably in pigmented cells, in
      several species. In humans, haploinsufficiency of MITF causes Waardenburg
      syndrome type 2, while a dominant-negative mutation causes Tietz syndrome. Four
      isoforms have been cloned so far: MITF-M is the most abundant and is expressed in
      neural-crest-derived melanocytes; MITF-A is expressed in various cultured cells
      including retinal pigment epithelium (RPE) and enriched in RPE of embryonal and
      developing eyes; MITF-H are expressed in many types of cultured cells and in the
      heart tissue; MITF-C is expressed in many types of cultured cells, but not in
      melanocytes. Many growth factor signaling pathways have been implicated for
      regulation of MITF at both protein and promoter levels. Most notably, Steel
      factor/c-Kit signaling pathway was linked to phosphorylation of MITF at Ser73 and
      Ser409 through activation of MAP kinase and RSK-1, respectively. Phosphorylation
      of MITF is also conducted at Ser298 through GSK3beta, although the signaling
      pathway for this event still remains to be elucidated. IGF-1 and HGF/SF pathways
      may merge with the c-Kit signaling pathway. WNT and MSH signaling pathways
      regulate MITF positively at the promoter level. Endothelins may regulate MITF at
      the protein and promoter levels. MITF is involved in the differentiation, growth
      and survival of pigment cells, employing a number of signaling pathways.

PMID- 10952393
TI  - Melanocyte subpopulation turnover during the human hair cycle: an
      immunohistochemical study.
AB  - The human hair cycle is characterized by successive phases of growth and
      involution that imply tissue regression and regeneration. As a consequence, the
      hair melanin unit has to be renewed in a cyclic manner. Actually, the behavior of
      human hair follicle melanocytes throughout the hair cycle has been poorly
      studied. Thus, the origin of melanocytes present in the bulb after human hair
      regeneration is still not clarified, and neither are the events that control the
      melanin biosynthesis activity in the human hair bulb. In this study, we showed at
      the cellular level that in human pigmented hair follicles, the expression of
      tyrosinase and tyrosinase-related protein-1 (TRP-1) was detectable during the
      anagen phases III/IV through VI, only in those melanocytes which were located in
      the bulb. During the catagen phase, the two evaluated melanogenic enzymes were
      detectable no more, although melanocytes were still present in the preceding
      bulbar area. The epithelial column of catagen follicles and the capsule of
      telogen follicles also contained inactive melanocytes as evidenced by pMel-17
      labeling. At the induction of a new anagen hair follicle, some melanocytes were
      committed to cell division, but only when located in the nascent bulb close to
      the dermal papilla. Our results emphasize the close relationship between
      melanogenesis and the hair cycle and suggest that in humans, melanogenesis is
      restricted to anagen hair follicles not because of the regulation of tyrosinase
      activity, but because of melanogenic enzyme expression, e.g., tyrosinase and TRP
      1. Furthermore, the fact that in the newly developing anagen hair follicles, cell
      division commitment and tyrosinase and TRP-1 expression were observed in
      melanocytes only when located in the nascent bulb suggests a highly regio
      specific melanocyte stimulation in early the anagen phase.

PMID- 10952392
TI  - Up-regulation of tyrosinase gene by nitric oxide in human melanocytes.
AB  - Ultraviolet light (UV) radiation causes skin-tanning, which is thought to be
      mediated by stimulating the release of melanogenic factors from keratinocytes as
      well as other cells. Nitric oxide (NO) has been reported to be generated after UV
      radiation and to stimulate melanocytes as one of the melanogens. In a previous
      experiment by another group on melanogenesis induced by NO, increases in both
      tyrosinase activity and tyrosinase protein levels were observed after daily
      stimulation of NO for 4 days. In the present study, we investigated tyrosinase
      gene expression within the first 24 hr of NO-induced melanogenesis. Tyrosinase
      mRNA expression was found to be induced 2 hr after a single treatment with S
      nitroso-N-acetyl-L-arginine. An increase of tyrosinase activity was also detected
      time-dependently within the 24-hr period, accompanied by an increase of
      tyrosinase protein levels. The induction of mRNA expression was suppressed by a
      cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (cGMP/PKG)
      inhibitor. These results suggest that the enhancement of tyrosinase gene
      expression via the cGMP pathway may be a primary mechanism for NO-induced
      melanogenesis.

PMID- 10952395
TI  - Spontaneous redox reactions of dopaquinone and the balance between the eumelanic
      and phaeomelanic pathways.
AB  - Eumelanogenesis and phaeomelanogenesis diverge at an early stage in pigment
      formation, namely at the point where dopaquinone, the initial product of tyrosine
      oxidation by tyrosinase, undergoes one of two types of reaction: either (1) a
      reductive endocyclisation in which a Michael addition of the side-chain amino
      group takes place; or (2) a reductive addition of cysteine to give cysteinyldopa.
      In the former case, the product cyclodopa, is known rapidly to undergo a redox
      exchange reaction with dopaquinone to yield dopachrome, the precursor of the
      eumelanogenic pathway. In the second instance, cysteinyldopa is regarded as
      leading to the formation of benzothiazoles, which are characteristic of
      phaeomelanin. The precursor molecule of the phaeomelanic pathway is
      cysteinyldopaquinone. We have examined quantitatively the role of dopaquinone in
      the non-enzymatic oxidation of 5-S-cysteinyldopa using pulse radiolysis and have
      demonstrated that the redox exchange reaction between dopaquinone and 5-S
      cysteinyldopa occurs spontaneously with a rate constant of 8.8 x 10(5) M(-1) sec(
      1). This study has also enabled an improved estimate of < or = 4 x 10(7) M(-1)
      sec(-1) to be obtained for the rate constant of the reaction of dopaquinone with
      cyclodopa. Calculations utilising these figures and estimates of the rate
      constants for the other reactions in early melanogenesis, demonstrate that,
      whilst similar pathways are invoked, the phaeomelanic pathway predominates in the
      presence of cysteine, irrespective of the availability of dopaquinone and thus
      independently of the rate of tyrosinase-catalysed oxidation. This suggests that
      the balance between the formation of eumelanin and phaeomelanin is regulated
      principally by the availability of cysteine at the site of melanogenesis.

PMID- 10952394
TI  - Plasticity of cadherin-catenin expression in the melanocyte lineage.
AB  - Cadherins are calcium-dependent cell adhesion receptors with strong
      morphoregulatory functions. To mediate functional adhesion, cadherins must
      interact with actin cytoskeleton. Catenins are cytoplasmic proteins that mediate
      the interactions between cadherins and the cytoskeleton. In addition to their
      role in cell-cell adhesion, catenins also participate in signaling pathways that
      regulate cell growth and differentiation. Cadherins and catenins appear to be
      involved in melanocyte development and transformation. Here, we investigated the
      function of cadherin-catenin complexes in the normal development and
      transformation of melanocytes by studying the patterns of expression of the cell
      cell adhesion molecules, E-, N- and P-cadherin, and the expression of their
      cytoplasmic partners, alpha-, beta- and gamma-catenin during murine development.
      Similar analyses were performed in vitro using murine melanoblast, melanocyte,
      and melanoma cell lines in the presence and absence of keratinocytes, the cells
      with which melanocytes interact in vivo. Overall, the results suggest that the
      expression of cadherins and catenins is very plastic and depends on their
      environment as well as the transformation status of the cells. This plasticity is
      important in fundamental cellular mechanisms associated with normal and
      pathological ontogenesis, as well as with tumorigenesis.

PMID- 10952397
TI  - Hypothesis: vitiligo virus.

PMID- 10952396
TI  - Melanocytes respond to mechanical stretch by activation of mitogen-activated
      protein kinases (MAPK).
AB  - Cells of human epidermis are permanently targeted by mechanical stimuli. Besides
      mechanical forces from external sources the body itself generates mechanical
      forces via muscle contractions and growth processes. Recently, it was
      demonstrated that mechanical stretch is connected to enhanced proliferation in
      epidermal cells. The underlying biochemical events are still a matter of debate.
      Here we show that mechanical stretch leads to activation of both ERK1/2 and
      SAPK/JNK in human melanocytes and keratinocytes. In response to a 5 min single
      stretch ERK1/2 becomes moderately induced in melanocytes and peaked 30 min after
      the stimulus. In keratinocytes strong activation of ERK1/2 is present directly
      after the stimulus. SAPK/JNK shows the same activation pattern in both cell
      species--a slow but steady activation. The different kinetics of both MAPK
      suggest that different signalling cascades were activated. Future studies should
      evaluate the relevance of stretch-dependent MAPK activation in triggering the
      cell proliferation.

PMID- 10952398
TI  - Melanins, melanogenesis and melanocytes: looking at their functional significance
      from the chemist's viewpoint.

PMID- 10952399
TI  - The pancreas and inflammatory bowel diseases.
AB  - This article reviews the literature and gives an overview on prevalence and
      possible explanations for pancreatic involvement in inflammatory bowel diseases
      (IBD). IBD patients have a markedly elevated risk for developing acute
      pancreatitis as well as pancreatic insufficiency. Multiple potential causes for
      pancreatitis in IBD patients exist. In the majority of cases acute pancreatitis
      appears to be related to drug side effects or local structural complications
      rather than a true extraintestinal manifestation of IBD. Nevertheless, some cases
      of acute pancreatitis remain unexplained. Prevalence of chronic pancreatitis in
      IBD patients also seems to be relatively high. However, etiology of pancreatic
      duct changes and/or the occurrence of exocrine insufficiency remain unclear. In
      most cases chronic pancreatitis is clinically unapparent, although in some
      patients it may be accompanied by clinically relevant exocrine insufficiency.

PMID- 10952400
TI  - Intraductal papillary mucinous tumors of the pancreas. Verona University
      Pancreatic Team.
AB  - METHODS: Literature is thoroughly reviewed and compared to our own experience.
      RESULTS: Clinical history data do not appear to be useful in differentiating
      between benign and malignant cases. Usually IPMT patients are older than
      individuals suffering from chronic obstructive pancreatitis and tend to drink and
      smoke less. Malignant forms of IPMT are more frequently associated with diabetes,
      and pain seems to be more frequent in benign cases, although these findings are
      not confirmed in all reports. Also, laboratory tests are of little use, whereas
      imaging findings currently enable us to reach a correct diagnosis in about 70% of
      cases without differentiating in a reliable and definitive way the benign or
      malignant nature of the neoplasm. The WHO classification appears to be related to
      the different prognosis. Surgery, whenever possible, is the gold standard
      treatment. CONCLUSION: IPMT are a recent established clinical entity embracing a
      spectrum of lesions ranging from benign to malignant infiltrating cases. The only
      recognized radical treatment is surgery. Despite diagnostic capacity based on
      clinical presentation and imaging techniques has becoming increasingly refined we
      are still incapable of identifying the different degree of malignancy
      preoperatively, if any. The lengthy mean survival after resection confirm the
      high potential cure rate of IPMT of the pancreas.

PMID- 10952401
TI  - Acute taurodeoxycholate-induced pancreatitis in the rat is associated with
      hyperCCKemia.
AB  - BACKGROUND: Cholecystokinin (CCK) has been suggested to be involved in the
      development and course of acute pancreatitis. In the present study we measured
      plasma CCK concentrations in acute experimental pancreatitis (AEP) in the rat,
      and evaluated the role of circulating CCK levels on the initial pancreatic damage
      in pancreatitis. METHODS: Endogenous hyperCCKemia was induced by surgical
      biliodigestive shunt (BDS) and exogenous hyperCCKemia by infusion of CCK-8S. The
      CCK-A receptor antagonist devazepide was used to antagonize the effect of CCK.
      Pancreatitis was induced by pancreatic duct infusion of sodium taurodeoxycholate
      4 wk after the BDS operation or 1 wk after the start of the infusions.
      Nonpancreatitic sham- and BDS-operated rats, respectively, were used as control
      animals as were groups of otherwise untreated rats with pancreatitis. The animals
      were sacrificed 6 h after induction of pancreatitis. Concentrations of CCK were
      determined in plasma as were protein and amylase levels in the pancreas and
      peritoneal exudates. The extent of pancreatic necroses was assessed
      microscopically. RESULTS: Pancreatitis caused an 11-20-fold increase of
      circulating CCK as measured after 6 h. In pancreatitic rats with induced
      hyperCCKemia, there was a further marked increase of plasma CCK. Pancreatic
      weight and edema, protein and amylase contents, and extent of necroses were the
      same regardless of the level of plasma CCK. Devazepide had no influence on the
      studied pancreatic parameters. CONCLUSION: We conclude that acute
      taurodeoxycholate-induced pancreatitis in the rat is associated with elevated
      plasma CCK concentrations. There seems, however, not to be any correlation
      between the degree of hyperCCKemia and the extent of initial pancreatic damage.

PMID- 10952402
TI  - Long-term ingestion of cassava (tapioca) does not produce diabetes or
      pancreatitis in the rat model.
AB  - Cassava (tapioca, manihot) is consumed as a staple food in some developing
      countries. The intake of cassava has been linked to several diseases including
      fibrocalculous pancreatic diabetes (tropical calcific pancreatitis). There are
      few long-term studies on the effect of cassava ingestion on the pancreas in
      animal models. This article reports on the long-term (up to 1 yr) effects of
      cassava in the rat model. We found that cassava did not produce diabetes in the
      rat even after a year of cassava feeding. There were transient changes in serum
      insulin and lipase levels, but the significance of these findings are not clear.
      There was no histopathological evidence of either acute or chronic pancreatitis,
      but there were changes of toxic hepatitis in the liver. In conclusion, chronic
      cassava ingestion up to a year does not lead to either diabetes or chronic
      pancreatitis in the rat model.

PMID- 10952403
TI  - Oxidative stress in distant organs and the effects of allopurinol during
      experimental acute pancreatitis.
AB  - BACKGROUND: The present study was aimed at an assessment of the role of oxygen
      derived free radicals in the development of local and systemic manifestations of
      L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the
      protective effect of the xanthine oxidase inhibitor allopurinol. METHODS: Acute
      pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body
      weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15
      M NaCl. Control rats received the same quantity of glycine. In a third group, 200
      mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg
      injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration.
      Acute pancreatitis was confirmed by a serum amylase level elevation and typical
      inflammatory features were observed microscopically. Tissue concentrations of
      malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione
      peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney.
      RESULTS: The tissue concentration of MDA was significantly elevated in each
      organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly
      depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities
      were reduced in the liver after the onset of pancreatitis. Histologic examination
      revealed acinar cell necrosis in the pancreas, but only mild alterations in the
      liver and kidney. Allopurinol pretreatment prevented the generation of reactive
      oxygen metabolites in the pancreas and reduced their formation in the kidney.
      CONCLUSION: Oxygen-derived free radicals are generated in the pancreas, liver,
      and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the
      kidney, but not the pancreas, are able to defend against oxidative stress. The
      prophylactic application of allopurinol significantly restrains the generation of
      free radicals in pancreas and kidney.

PMID- 10952404
TI  - Long-term survival after multimodality treatment for resectable pancreatic
      cancer.
AB  - BACKGROUND: The prognosis of pancreatic adenocarcinoma after radical
      pancreatectomy is poor, especially in advanced-stage disease. STUDY AIM: To
      determine the survival rates and evaluate the effectiveness of multimodality
      treatment for advanced pancreatic cancer. METHODS: From November 1983 to January
      1993, 30 patients with pancreatic adenocarcinoma including 9 with carcinoma of
      the body and tail were treated by a multimodal approach consisting of extended
      pancreatectomy, intraoperative radiotherapy (IORT), and hepatic artery or portal
      vein infusion of mitomycin C (MMC) followed by systemic bolus injection. All
      surviving patients were followed for more than 8 yr and survival rates were
      calculated by the Kaplan-Meier method. RESULTS: There were no operative or
      hospital deaths. Eight patients survived for more than 5 yr, 3 of whom survived
      more than 10 yr. The 5-yr survival rate for 27 patients excluding 3 with
      metastasis to the liver, peritoneum, or lung was 31%, with a median survival of
      31.1 mo. Among them, the 1-, 3-, and 5-yr survival rates for 19 patients with
      regional nodal metastasis were 95, 50, and 28%, respectively, with a median
      survival of 36.0 mo. CONCLUSION: The multimodality treatment combined with IORT
      and MMC chemotherapy appeared to have a benefit for prognosis of advanced
      pancreatic adenocarcinoma.

PMID- 10952405
TI  - Intra-arterial continuous infusion for treatment of pancreatic and biliary tract
      cancer.
AB  - BACKGROUND: Systemic chemotherapy does not satisfactorily improve the poor
      prognosis of pancreas and biliary tract cancer unresectable or metastatic to the
      liver. Intra-arterial infusion of antineoplastic agents can give higher
      concentrations to the tumor and slighter concentrations to the whole body, with a
      potential of efficacy and lower toxicity, due to the hepatic clearance. METHODS:
      Based on a safe and ambulatorial technique of transcutaneous arterial port
      implantation, this study was designed to evaluate feasibility and toxicity of 5
      fluorouracil (5-FU) intra-arterial continuous infusion combined with systemic
      gemcitabine with dose escalation. Seventeen patients affected by pancreatic (14)
      or biliary tract (3) cancer received up to six cycles of treatment. Treatment
      consisted of intravenous gemcitabine on d 1 and 8 and intra-arterial 5-FU
      continuous infusion on d 1-14 every 21 d. Dose-escalation levels were 900 and
      1000 mg/m2 for gemcitabine and 8, 10, 12, 15, and 17 mg/kg/d for 5-FU.
      Consecutive cohorts of three patients were planned at each dose level. RESULTS:
      Gastrointestinal toxicity (vomiting and diarrhea [3rd-4th degree] and gastritis),
      constituted the dose-limiting toxicity, with a maximum-tolerated dose of 1000
      mg/m2 for gemcitabine and 15 mg/kg/d for 5-FU. Hematological toxicity was present
      in a minority of patients. No patient had acute or later complications such as
      arterial thrombosis related to the implanted arterial port, sclerosis
      cholangitis, or chemical cholecistitis. CONCLUSION: 5-Fluorouracil intra-arterial
      continuous infusion, combined with systemic gemcitabine, seems to be a feasible
      and safe regimen that could give interesting results in pancreatic cancer.

PMID- 10952407
TI  - Pleomorphic carcinoma of the pancreas with massive lymphocytic stromal
      infiltration and long-term survival after resection.
AB  - BACKGROUND: Pleomorphic carcinoma of the pancreas is a rare tumor with an
      extremely poor prognosis. The mean survival time is reported to be approx 3 mo.
      CLINICAL AND HISTOLOGICAL FINDINGS: A 56-yr-old Japanese man presenting with
      general fatigue, loss of weight, and high fever was found to have a large
      hypervascular mass in the body of the pancreas with regional lymph node
      metastases. Laboratory investigation revealed leukocytosis, elevated erythrocyte
      sedimentation rate (ESR), and high serum C-reactive protein (CRP). In addition to
      distal pancreatectomy, splenectomy and lymph node dissection were performed.
      Histology showed the presence of pleomorphic large cells with bizarre mono- or
      multinuclei, growing in sarcomatoid pattern without mutual cohesiveness. Another
      noticeable finding was massive lymphocytic infiltration of the stroma of the
      neoplasm. Immunohistochemically, the infiltrating lymphocytes consisted of
      cytotoxic type of T cells. In addition, in situ hybridization for Epstein-Barr
      virus-encoded RNA (EBAR-1) was not seen in the tumor cells or in lymphocytes.
      After surgery the patient did not undergo chemotherapy or radiotherapy. He has
      been well without recurrence for 8 yr. CONCLUSION: We report a case of
      pleomorphic carcinoma, possibly lymphoepithelioma-like carcinoma, of the pancreas
      with massive lymphocytic stromal infiltration and long-term survival after
      resection. Cytokine responses and cellular immunoreactivity may have contributed
      to a long-term survival, which is unusual in the common type of pleomorphic
      carcinoma of the pancreas.

PMID- 10952406
TI  - Opioid treatment of painful chronic pancreatitis.
AB  - BACKGROUND: Abdominal pain is the dominant symptom in 50-75% of patients with
      chronic pancreatitis, often requiring opioid analgesics. Fentanyl, a potent
      synthetic opioid, can be administered percutaneously at a constant dose and is
      claimed to have fewer systemic side effects. AIM: To evaluate transdermal
      fentanyl plaster versus sustained release morphine tablets as analgesic treatment
      of painful chronic pancreatitis. METHODS: In an open randomized crossover trial,
      18 patients were included. The treatment period was 4 wk for each drug. All
      patients had immediate-release morphine tablets as rescue medication. RESULTS:
      The dosage of transdermal fentanyl had to be increased on average 50% over that
      indicated by the manufacturer. When this was done and rescue medication was
      secured, no difference between the two drugs in primary endpoint or patient
      preference was observed. There was also no difference in the secondary endpoints,
      pain control, and quality of life. However, skin side effects, mostly mild,
      occurred in 44% of the patients during treatment with transdermal fentanyl, and
      the mean daily dose of immediate release morphine was significantly higher during
      the transdermal fentanyl period than during the sustained-release morphine period
      (30.7 mg vs. 14.7 mg [p < 0.01]). CONCLUSION: When given in an appropriate dose,
      transdermal fentanyl might be useful for treatment of some patients with painful
      chronic pancreatitis, e.g., when tablet ingestion is difficult. However, the
      dosage often has to be increased above that recommended by the manufacturer. The
      need of rescue morphine is considerable and skin side effects often occur.
      Transdermal fentanyl is, therefore, not the ideal first-choice analgesic in
      patients with painful chronic pancreatitis.

PMID- 10952408
TI  - A case of mixed acinar-endocrine carcinoma of the pancreas discovered in an
      asymptomatic subject.
AB  - A 50-yr-old Japanese man was found to have a hypoechoic mass 3 cm in diameter in
      the pancreatic head on an ultrasonography (US) examination without symptoms. A
      computed tomography (CT) scan demonstrated a 3-cm solid mass in the pancreatic
      head, and it was more clearly delineated as a low-density area on enhanced CT.
      Angiography showed a tumorlike stain, 3 cm in size, in the pancreatic head. The
      preoperative diagnosis was "special type of pancreatic tumor such as acinar cell
      carcinoma or non-functioning islet cell tumor." The patient was treated by
      pylorus-preserving pancreatoduodenectomy. Histological, immunohistochemical, and
      electron-microscopic studies of the surgical specimen led to a definitive
      diagnosis of a mixed acinar-endocrine carcinoma. The patient is currently well,
      with no signs of tumor recurrence, 18 mo after the operation. Our search of the
      Japanese and English-language literature retrieved only 15 well-documented cases
      of mixed acinar-endocrine carcinoma. Imaging in the reported cases revealed
      features of either acinar cell carcinoma or islet cell tumor, or both, which can
      may be detected even in small tumors more easily than conventional invasive
      ductal carcinoma of the pancreas because the detectability of this rare tumor on
      US and CT seems to be good.

PMID- 10952409
TI  - Veterinary sources of nonrodent monoclonal antibodies: interspecific and
      intraspecific hybridomas.
AB  - The generation of monoclonal antibodies from species other than rats and mice has
      developed slowly over the last 20 years. The advent of antibody engineering and
      realization of the advantages of nonmurine antibodies, in terms of their superior
      affinities and specificities, and their potential as components of human and
      veterinary therapeutics has increased their relevance recently. There have been
      significant advances in the development of myeloma and heteromyeloma fusion
      partners. This is an opportune moment to consolidate experiences of MAb
      production across the range of species of veterinary interest and place it into
      context with other developments in the field of monoclonal antibodies. The
      background to the development of antibodies from species other than the mouse is
      discussed. The species and antigens used to date are reviewed, as are the methods
      and results reported. A suggested protocol is provided for first attempts to
      exploit the huge potential of this aspect of hybridoma technology and suggestions
      are made for its further expansion.

PMID- 10952410
TI  - Antibody binding regions on human nerve growth factor identified by homolog- and
      alanine-scanning mutagenesis.
AB  - The binding specificities of a panel of mouse monoclonal antibodies (MAbs) to
      human nerve growth factor (hNGF) were determined by epitope mapping using
      chimeric and point mutants of NGF. Subsequently, the MAbs were used to probe NGF
      structure-function relationships. Six MAbs, which recognize distinct or partially
      overlapping regions of hNGF, were evaluated for their ability to block the
      binding of hNGF to the TrkA and p75 NGF receptors in various in vitro assays,
      which included blocking of TrkA autophosphorylation and blocking of NGF-dependent
      survival of dorsal root ganglion sensory neurons. Three MAbs (911,912,938) were
      potent blockers of all activities. Potent blocking of p75 binding occurs only
      with MAb 909, which recognizes an NGF region identified by mutagenesis as
      important for NGF-p75 binding. These results are consistent with recently
      proposed models of binding regions involved in NGF-TrkA and NGF-p75 interactions
      generated through mutagenic analysis and structure determination of the NGF-TrkA
      complex. These studies provide insight to the epitope specificities and potency
      of MAbs that would be useful for physiological NGF blocking studies.

PMID- 10952412
TI  - A mouse IgG1 monoclonal antibody specific for N-glycolyl GM3 ganglioside
      recognized breast and melanoma tumors.
AB  - 14F7 murine monoclonal antibody (MAb) is an IgG1 immunoglobulin that is generated
      by immunizing Balb/c mice with GM3(NeuGc) ganglioside hydrophobically conjugated
      with human very-low-density lipoproteins and in the presence of Freund's
      adjuvants. 14F7 MAb binds specifically to GM3(NeuGc), whereas neither N-glycolyl
      or N-acetyl gangliosides, nor a sulfated glycolipid, are recognized as assessed
      by enzyme-linked immunosorbent assay or immunostaining on thin layer
      chromatograms. Immunohistochemical studies in fresh tumor tissues showed that
      14F7 MAb strongly recognized in antigen expressed in human breast and melanoma
      tumors.

PMID- 10952411
TI  - Production and functional characterization of two mouse/human chimeric antibodies
      with specificity for the tumor-associated Tn-antigen.
AB  - In this work, we have constructed two functional mouse/human chimeric antibodies
      (IgMkappa and IgG1kappa isotypes) by inserting genomic DNA fragments encoding VH
      and Vkappa variable regions of the murine monoclonal antibody IgMK-83D4 into
      mammalian expression vectors containing human mu, gamma1, and kappa constant
      exons, and by transfecting them into the nonsecreting mouse myeloma X-63 cell
      line. In previous works, we have demonstrated that 83D4 murine mAb reacts with Tn
      determinant (GalNAcalpha-O-Ser/Thr) expressed in 90% of breast, ovary, and colon
      carcinomas. Both expressed chimeric antibodies were purified from the transfected
      cell line supernatant by affinity chromatography, and their reactivities against
      Tn antigen were confirmed by ELISA on asialo ovine submaxilar mucin and
      immunofluorescence studies on MCF-7 breast carcinoma cell line. We have
      demonstrated by gel filtration chromatography, that the principal secreted forms
      were monomers for IgG1kappa and pentamers for IgMkappa. The binding affinities of
      these chimeric antibodies against synthetic Tn glycopeptides, were evaluated by
      surface plasmon resonance showing an affinity constant similar to that of 83D4
      native antibody for IgMkappa and a lower affinity constant for IgG1kappa chimeric
      antibody. On the other hand, the replacement of mouse C regions with human C
      regions confers both chimeric antibodies the ability to activate human
      complement. These mouse/human chimeric antibodies should be much less immunogenic
      and could play an important role in the lysis of tumor cell expressing Tn
      antigen. Therefore, these anti-Tn chimeric antibodies could be considered as
      potential tools for human in vivo studies.

PMID- 10952413
TI  - Isolation and characterization of monoclonal antibodies specific for protein
      conformational epitopes present in prostate-specific membrane antigen (PSMA).
AB  - Prostate-specific membrane antigen (PSMA) is a 750-amino acid glycoprotein highly
      expressed in malignant prostate tissues. PSMA reacts with the murine monoclonal
      antibody 7E11.C5, whose binding epitope has been mapped to the N-terminal of the
      protein distributed on the cytoplasmic side of the plasma membrane. We have
      developed murine monoclonal antibodies specific for extracellular epitopes of
      PSMA. Three of these antibodies--1G9, 3C6, and 4D4--display distinct binding
      properties consistent with their recognition of conformational epitopes within
      native PSMA. Results indicate this panel of antibodies binds to native full
      length PSMA, but not to fusion proteins containing portions of the linear
      sequence of the protein. Antibody binding is greatly reduced upon heat
      denaturation of native PSMA, and these antibodies do not detect PSMA by Western
      blot. Immunoprecipitation experiments demonstrate the ability of each to bind to
      full-length PSMA as well as PSM', a form of the protein missing the first 57
      amino acids. These results indicate each antibody is specific for an epitope
      within the extracellular domain, a region spanning residues 44-750. Flow
      cytometric experiments indicate strong specific binding to live LNCaP cells.
      Antibody inhibition studies demonstrate that these antibodies recognize at least
      two distinct epitopes. Taken together, the results demonstrate that these
      antibodies are specific for native protein conformational epitopes within the
      extracellular domain. Their properties, in particular strong binding to live
      cancer cells, make them ideal candidates that are clearly superior to linear
      sequence epitope specific antibodies for in vivo applications.

PMID- 10952414
TI  - Monoclonal antibodies against hepatitis B s antigen: production,
      characterization, and use for diagnosis.
AB  - Three different hybridoma clones secreting anti-HBsAg antibody were constructed
      by fusing cells of mouse myeloma line Ag8-X63 with splenocytes from BALB/c mice
      immunized with recombinant HBsAg and natural HBV. The monoclonal antibodies
      obtained were characterized immunologically, and two were used to develop UMELISA
      for detection of HBsAg. This monoclonal assay enabled the detection of 0.1 UPE/mL
      with reference to the standard of the Paul Ehrlich Institute (Frankfurt,
      Germany). The assay compared well with a commercially available kit (UMELISA
      HBsAg) and was used for detection of HBsAg in blood donors.

PMID- 10952415
TI  - Production, characterization, and uses of monoclonal antibodies against porcine
      reproductive and respiratory syndrome virus 3' untranslated region and
      nucleoprotein RNA binding proteins.
AB  - Previous studies in our laboratory of interactions between the 3' untranslated
      region of porcine reproductive and respiratory syndrome virus (PRRSV) and MARC
      145 cell cytoplasmic proteins have identified 11 RNA binding proteins. Here, we
      report the production and characterization of monoclonal antibodies (MAbs)
      against a 67-kD RNA binding protein of MARC 145 tissue cultured cells. Of the
      MAbs produced, 11 were reactive in ELISA with 67-kD protein. Immunoprecipitation
      tests showed that six clones precipitated a protein of 67 kD, and one clone
      recognized a multiple protein bands of 45, 37, and 27 kD. Western blotting showed
      that these clones detected two proteins of 67 and 55 kD. Indirect fluorescent
      antibody staining of testing of PRRSV-infected cells with these MAbs revealed
      diffuse cytoplasmic staining and intense perinuclear staining to one side of the
      nucleus. The presence of the double membrane vesicles in the same region in PRRSV
      infected alveolar macrophages suggests that these RNA binding proteins might have
      a role in their formation.

PMID- 10952416
TI  - Lewis antigens and argyrophilic nucleolar organizer regions staining for
      assessment of potential malignancy of adenomatous polyps of the gastrointestinal
      tract in children.
AB  - Adenomatous polyps (AP) of the gastrointestinal tract in children are very rare.
      Because of their potential malignancy, they are of great clinical importance.
      There is little experience in the management of children with AP. The
      immunohistochemical expression of the Lewis blood group antigens (BGA) (sialosyl
      Le(a), Le(a), Leb, Le(x), and Le(y)) and the number of activated nucleoli with
      the silver staining method for nucleolar organizer regions (AgNORs) were studied
      in two children with AP. In a girl with isolated AP of the stomach and colon, it
      was found that antigens Le(b) and s-Le(a) were expressed extensively in the
      gastric adenoma, and sialosyl-Le(a) throughout the entire length of the rectal
      adenoma crypts, but in the AgNORs stain the number of nucleoli ranged from two to
      four, evidencing changes of a benign character. In the case of familial
      adenomatous polyposis diagnosed in a 9-year-old boy, in some colonic adenomas the
      number of activated nucleoli was greater than five, and the Le(b) antigen was
      expressed in superficial epithelial cells in one of the adenomas. Also, extensive
      expression of antigens Le(y) and s-Le(a) throughout the entire length of the
      crypt in another polyp removed was observed. We believe that immunohistochemical
      study of the intensity and extent of the expression of Lewis BGA in the polyp
      tissue simultaneously with the determination of the number of activated nucleoli
      by the AgNORs staining method can be helpful in better analysis of cytological
      risk factors of a malignant transformation.

PMID- 10952417
TI  - Advances in the molecular mechanisms of heart failure.
AB  - Congestive heart failure is a common clinical problem resulting in significant
      morbidity and mortality. Although considerable progress has been made in
      elucidating the pathophysiologic mechanisms that lead to the development of this
      process, much remains unknown. The techniques of modern molecular biology now
      allow a detailed and systematic analysis of this disease. Recent data linking
      cardiac hypertrophy, aberrant signaling, or cytoskeletal abnormalities to the
      development of heart failure have provided new insights into this process. These
      studies have confirmed the importance of many classical pathways but also
      revealed novel pathways. This review will focus on the recent advances that have
      been made and will highlight the importance they have had in our understanding
      and treatment of heart failure.

PMID- 10952418
TI  - Endothelin-1: a new target of therapeutic intervention for the treatment of heart
      failure.
AB  - Endothelin-1 has been appreciated in animals and humans as a potential target for
      inhibition in patients with acutely decompensated congestive heart failure (CHF),
      as well as patients with a chronic low-output state. There has been intense
      interest in determining the effects of endothelin-1 on the cardiovascular system.
      Elevated plasma levels of endothelin-1 in patients with CHF portend a poorer
      prognosis than similar patients without elevated levels. Endothelin-1 levels
      correlate inversely with maximum oxygen consumption, and inhibition of the
      myocardial endothelin pathway in rats with CHF improves survival. An association
      between endothelin-1 and the development of CHF has recently been supported.
      Selectively inhibiting the endothelin A receptors in dogs with CHF produced
      hemodynamic improvement. Similarly, in rabbits, a structural advantage was
      demonstrated. Benefits in cardiac remodeling have been demonstrated in several
      models of CHF by nonselectively antagonizing endothelin receptors. In human
      trials using nonselective endothelin-1 inhibitors, researchers have demonstrated
      hemodynamic benefit and improvement in cardiac function in patients with
      decompensated CHF. Inhibition of endothelin-1 in patients with CHF appears to
      have potential therapeutic value, and ongoing clinical trials will further
      investigate the safety, efficacy, and role of this new potential therapeutic
      target for the treatment of CHF.

PMID- 10952419
TI  - Renin angiotensin system and ASCVD.
AB  - The renin angiotensin system was first described over 100 years ago and is still
      the focus of intense clinical and basic science investigation. The renin
      angiotensin system was demonstrated to play a major pathogenetic role in
      hypertension. The development of inhibitors of angiotensin-converting enzyme and
      specific receptor blockers for angiotensin-II represent a major advance in the
      treatment of elevated blood pressure. However, the renin angiotensin system is
      intimately involved in a number of conditions that increase the risk for
      atherosclerosis. Components of the renin angiotensin system have demonstrated to
      play a significant role in the initial phases of atherosclerosis. Additionally,
      plaque vulnerability and the potential for an acute atherosclerotic event are
      also modulated by the renin angiotensin system. Angiotensin-II plays a
      significant role in the balance between intravascular clot formation and
      fibrinolytic potential. Therefore, blocking the generation of angiotensin-II or
      inhibiting its binding to specific receptors may decrease the subsequent risk for
      unstable angina and acute myocardial infarction. Increased renin activity has
      been correlated as a statistical risk factor for coronary heart disease and
      converting enzyme inhibition has been demonstrated to decrease the incidence of
      acute ischemic events. This review will center on the role of modulation of the
      renin angiotensin system as a means to alter the clinical course of coronary
      atherosclerosis.

PMID- 10952420
TI  - Noninvasive assessment of hemodynamics: an emphasis on bioimpedance cardiography.
AB  - Evaluation of the hemodynamic response in heart failure is a useful adjunct in
      clinical management. Invasive monitoring has been the accepted gold standard of
      hemodynamic assessment but carries with it significant associated risks.
      Noninvasive hemodynamic assessment in heart failure previously has been either
      unreliable or difficult to obtain. Bioimpedance relies on the proportional change
      in the conduction of alternating current applied across the thorax as a function
      of blood volume in the heart and great vessels. Stroke volume, cardiac output,
      thoracic fluid content, and measures of diastolic function can be determined with
      bioimpedance. Impedance cardiography is becoming an accepted method for safe,
      reliable, and reproducible assessment of hemodynamics in heart failure.

PMID- 10952421
TI  - Intravenous therapy for advanced heart failure.
AB  - Because of the standard use of oral neurohumoral antagonists, the role of
      intravenous agents for advanced heart failure patients has changed profoundly.
      Their current use as medical therapy is restricted to two indications: first, as
      short-term infusion (hours to days) in advanced heart failure patients who
      decompensate into a symptomatic New York Heart Association class IV condition and
      who are admitted for rapid hemodynamic support with intravenous vasodilators or
      inotropes; in these patients after hemodynamic and clinical stabilization,
      optimization of conventional heart failure therapy has to be reconsidered;
      second, as long-term application in heart transplantation candidates who are in a
      similar desperate condition although already receiving maximal oral heart failure
      therapy.

PMID- 10952422
TI  - Surgical therapies for heart failure.
AB  - Heart transplantation remains the best hope for patients with end-stage heart
      failure unresponsive to conventional therapy, but the number of transplant
      candidates continues to exceed the number of available donor hearts. Despite
      major advances in the medical management of heart failure, researchers continue
      to explore alternative surgical therapies designed to augment cardiac function.
      Many of these surgical therapies are still in the experimental or clinical trial
      phases. Surgical approaches include coronary revascularization, mitral valve
      repair or replacement, cardiomyoplasty, left ventricular volume reduction
      surgery, and bridging to recovery with the use of ventricular assist devices.
      Although cardiac surgeons have gained considerable experience in the treatment of
      patients with heart failure, many improvements and innovations lie ahead.

PMID- 10952423
TI  - Development and clinical application of the MicroMed DeBakey VAD.
AB  - A miniaturized axial flow pump to provide left ventricular assistance has been
      developed. Such a device has the potential to address limitations of the larger
      pulsatile devices. Clinical trials of the MicroMed DeBakey VAD (ventricular
      assist device) began in Europe in November 1998. As of December 1, 1999, 18
      patients have been implanted with the MicroMed DeBakey VAD. Hemodynamic
      evaluations along with blood chemistry analysis were recorded routinely. Exercise
      tolerance was observed. In most patients, end-organ function has improved and has
      not deteriorated in any patient. Patients have been able to perform normal low
      level activity and have tolerated positional changes without evidence of postural
      hemodynamic changes. Select patients have taken supervised out-of-hospital
      excursions. This initial clinical experience with the MicroMed DeBakey VAD
      suggests that the miniaturized axial flow pump can provide ventricular support to
      bridge patients to cardiac transplant and may provide an improved quality of life
      for the end-stage heart failure recipient.

PMID- 10952424
TI  - New treatment methods for patients with hypertrophic obstructive cardiomyopathy.
AB  - The past decade has witnessed significant advancements in the treatment of
      patients with refractory symptoms due to hypertrophic obstructive cardiomyopathy.
      In this publication, we will review the impact of dual-chamber pacing and
      nonsurgical septal reduction therapy with ethanol on the outcome of these
      patients. Both therapies have been shown to result in significant reductions in
      the left ventricular outflow gradient, which was an entry criterion in all the
      reported studies, along with symptomatic relief from symptoms of angina and
      dyspnea on midterm follow-up. Studies currently are under way to compare dual
      chamber pacing and nonsurgical septal reduction therapy with myotomy-myomectomy,
      which is considered to be the standard of care in these patients.

PMID- 10952425
TI  - Cardiac transplantation: the final therapeutic option for the treatment of heart
      failure.
AB  - End-stage heart failure is still associated with a decrease in quality and
      prognosis of life. Cardiac transplantation remains the final extraordinary
      therapeutic option for the treatment of truly irreversible end-stage heart
      failure in all age groups. The selection process of candidates and the acceptance
      of patients with relative contra-indications is characterized by the experience
      and skills of an interdisciplinary transplant team, which should have access to
      different mechanical circulatory support systems for short-term or long-term use:
      bridging to transplant as well as for recovery.

PMID- 10952426
TI  - Apoptosis and cardiomyopathy.
AB  - Apoptosis is a form of cell death that has been described as distinct from
      necrotic cell death. It is believed to be genetically programmed and occurs as a
      physiologic process in various organ systems of body. Although it has been
      tacitly believed that apoptosis does not occur in the terminally differentiated
      adult heart muscle cells, studies in endomyocardial biopsies from patients with
      dilated and ischemic cardiomyopathy and in explanted hearts from patients with
      end-stage heart failure undergoing cardiac transplantation have demonstrated
      histochemical evidence of apoptosis. It has been proposed that ventricular
      dilatation and neurohormonal activation during heart failure lead to upregulation
      of transcription factors, induce myocyte hypertrophy, and prepare the cell for
      entry into the cell cycle. However, terminally differentiated myocytes cannot
      divide, and failing to divide they undergo apoptosis. Initiation of apoptosis is
      associated with activation of upstream cascade, including the release of
      cytochrome c from mitochondria to cytoplasm and the processing of proteolytic
      caspases. The activation of caspases leads to fragmentation of various
      cytoplasmic proteins, including contractile proteins. However, the nuclear
      fragmentation and condensation is completed only rarely. It is hypothesized that
      the release of cytochrome c from mitochondria and cytoplasmic protein loss in a
      living heart muscle cell should lead to systolic dysfunction.

PMID- 10952428
TI  - Models of dilated cardiomyopathy in the mouse and the hamster.
AB  - Dilated cardiomyopathy (DCM) is a heart muscle disorder characterized by atrial
      and ventricular dilation often with relative wall thinning, severe systolic and
      diastolic ventricular dysfunction, and frequent findings of heart failure. Using
      genetically engineered mice, a number of studies have attempted to determine the
      role of specific genes, as well as to mimic the phenotype of human DCM. Naturally
      occurring and acquired animal models of DCM also have been investigated. In this
      brief review, we will focus on small animal models of DCM, particularly those in
      the mouse, together with some comments on the autosomal-recessive cardiomyopathy
      of the hamster. These animal models can be categorized into several general
      groups in accordance with the presumed role of the gene mutation involved,
      including intrasarcomeric and extrasarcomeric cytoskeletal abnormalities, which
      resemble some forms of hereditary human DCM, and overexpression or disruption of
      genes that control molecules participating in intracellular signaling pathways,
      including the beta-adrenergic system and calcium regulation. Modifications in the
      latter two pathways can cause or alleviate DCM in animal models, suggesting their
      importance in myocyte adaptive and survival mechanisms.

PMID- 10952427
TI  - Animal models of hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (FHC) is an autosomal-dominant disease that
      is both clinically and genetically heterogeneous. Disease-causing mutations have
      been found in eight genes encoding structural components of the thick and thin
      filament systems of the cardiac myocyte; it has therefore been coined a disease
      of the sarcomere. How each mutation leads to the diverse clinical phenotypes is
      still obscure, and research in this area is very active. Many approaches have
      been used to characterize the pathogenesis of the disease. Biochemical
      characterization of mutant alleles expressed in vitro has shed some insight into
      the functional deficits of several mutant alleles of myosin heavy chain, troponin
      T, and alpha-tropomyosin. Transgenic animal models for FHC have been created to
      gain further insight into the pathogenesis of this disease. Most of these models
      have been made in mice; however, recently a transgenic rabbit model has been
      created. In addition, there are several natural-occurring forms of FHC in animals
      that will be interesting to explore. The discovery of additional responsible
      genes and the elucidation of the molecular mechanisms of pathogenesis through the
      use of animal models promise improved and early diagnosis and the potential for
      developing specific, mutation-, or mechanism-based therapeutics.

PMID- 10952429
TI  - Molecular aspects of arrhythmias associated with cardiomyopathies.
AB  - The increased risk of sudden cardiac death in patients with myocardial
      hypertrophy and heart failure is the result of remodeling that occurs in both the
      myocyte and interstitial compartments of the heart. Action potential prolongation
      is a hallmark of hypertrophied and failing myocardium and is a consequence of
      differential expression and function of membrane currents and transporters.
      Functional downregulation of K currents in the ventricle is a recurring theme in
      hypertrophy and failure; the reduction in the density of the transient outward
      current (I(to)) is the most consistent observation, whereas data on the density
      of the inward (I(K1)) and the delayed rectifier (I(K)) currents are more
      contradictory. The altered intracellular Ca handling of the myopathic hearts
      prolongs the decay of the L-type Ca current and favors extrusion of cytosolic
      Ca2+ via the Na+-Ca2+ exchanger. The interaction between such altered membrane
      currents and a changed neurohumoral milieu creates a substrate that is highly
      susceptible to potentially lethal ventricular arrhythmias.

PMID- 10952430
TI  - Bibliography. Current world literature. Cardiac failure.

PMID- 10952431
TI  - Bibliography. Current world literature. Molecular genetics.

PMID- 10952432
TI  - Head and neck cancer: overview of recent developments and future directions.

PMID- 10952433
TI  - Head and neck surgery in the era of organ preservation therapy.
AB  - The role of surgery in the treatment of head and neck cancer has evolved over the
      past few decades. Surgery continues to be the primary treatment modality for
      early disease and for lesions in which extirpation provides a high rate of
      disease control without substantial loss of function (eg, oral cavity). Despite
      nonsurgical approaches aimed at organ preservation (ie, combined chemotherapy and
      radiation therapy), surgery continues to have a role in chemoradiation treatment
      strategies as salvage therapy and as a part of a treatment modality designed to
      preserve vital organ function. Salvage surgery is generally used after disease
      failure following a nonsurgical treatment approach and includes primary
      persistent disease and neck recurrence. Several function-sparing surgical options
      are available for the larynx, oral cavity, hypopharynx, and tongue base,
      including laser excision, supraglottic and vertical hemilaryngectomy, Pearson
      near-total laryngectomy, and various reconstruction methods. Function-sparing
      surgery combined with chemotherapy is currently under investigation and may
      provide optimal survival and function in selected patients with head and neck
      cancer.

PMID- 10952434
TI  - The role of induction chemotherapy in the curative treatment of squamous cell
      cancer of the head and neck.
AB  - Induction chemotherapy is appropriate for the treatment of locally advanced
      squamous cell carcinoma of the head and neck because it allows organ preservation
      without compromising survival and improves survival in unresectable disease.
      Radiation therapy, not surgery, should immediately follow induction chemotherapy
      in potentially resectable patients to prevent tumor repopulation. The results of
      three phase II studies of docetaxel-based regimens as induction therapy of
      patients with locally advanced squamous cell carcinoma of the head and neck are
      reviewed and reported. Overall response rates ranged from 93% to 100%, with
      complete response rates of 40% to 63%. The primary toxicities were neutropenia
      and febrile neutropenia. A North American phase III trial, randomizing patients
      to docetaxel/cisplatin/fluorouracil or cisplatin/fluorouracil sequentially
      followed by chemoradiotherapy is being performed to determine whether docetaxel
      improves the complete response rate, organ preservation rate, and survival of
      patients treated with induction chemotherapy.

PMID- 10952435
TI  - Treatment of patients with recurrent or metastatic squamous cell carcinoma of the
      head and neck: current status and future directions.
AB  - Patients with advanced squamous cell head and neck cancer have a dismal long-term
      survival rate not only because of metastatic disease, but also primarily because
      of failure in local disease control. The role of chemotherapy in recurrent or
      metastatic head and neck cancer has largely been palliative. Several chemotherapy
      agents, including docetaxel, paclitaxel, and ifosfamide, have been extensively
      studied, either alone or in combination regimens, for the treatment of recurrent
      or metastatic disease. These have resulted in response rates that are similar or
      higher than those obtained with the gold standard combination, cisplatin/
      fluorouracil. Single-agent and combination studies of vinorelbine and gemcitabine
      have demonstrated modest activity in recurrent or metastatic disease. Phase III
      trials are planned that will compare taxane-based regimens with cisplatin and 5
      fluorouracil in recurrent or metastatic head and neck cancer. Meanwhile, new drug
      and compound development, including monoclonal antagonists to the epidermal
      growth factor receptor, farnesyl transferase inhibitors, and oncolytic viruses
      are being tested in this setting.

PMID- 10952436
TI  - The use of concurrent chemotherapy and radiotherapy for locoregionally advanced
      head and neck cancer.
AB  - The long-term prognosis of patients with advanced head and neck cancer has been
      poor. Combined modality approaches, such as induction chemotherapy, adjuvant
      chemotherapy, and concomitant chemoradiotherapy, have been studied in an effort
      to control local tumor and reduce systemic tumor dissemination. Randomized
      clinical trials and meta-analyses have both demonstrated a survival benefit with
      concomitant chemoradiotherapy, despite the omission of surgery. Because of both
      direct and indirect toxicities of concomitant chemoradiotherapy, less-toxic and
      equally effective strategies are being investigated. Concurrent chemoradiotherapy
      should be considered a possible standard therapy option for head and neck cancer
      patients and should be administered at treatment centers with experienced health
      care providers who have access to clinical trials.

PMID- 10952437
TI  - The current status of gene therapy.
AB  - Locoregionally recurrent head and neck squamous cell carcinoma is a logical
      target for direct delivery of gene therapy approaches. Because the protein p53
      plays a role in cell cycle regulation and in apoptosis, p53 gene transfer was
      initially tested in head and neck cancer patients by injecting the primary or
      regional tumor with an adenoviral vector possessing wild-type p53. Adenoviral p53
      was demonstrated to be safe and well tolerated; furthermore, activity was
      observed. Several randomized studies of adenoviral p53 are now under way in
      patients with head and neck squamous cell carcinoma to determine its role as a
      surgical adjuvant in untreated disease and in combination with DNA-damaging
      agents.

PMID- 10952438
TI  - Hazard analysis and critical control point (HACCP) approach and food safety as
      well as Legislation.

PMID- 10952439
TI  - Highly cited article published in the Veterinary Quarterly in 1991.
AB  - In early 1991, the Dutch pig industry was struck by the so-called mystery swine
      disease. Large-scale laboratory investigations were undertaken to search for the
      aetiological agent. We focused on isolating viruses and mycoplasmas, and we
      tested paired sera of affected sows for antibodies against ten known pig viruses.
      The mycoplasmas M. hysonoviae, M. hyopneumoniae, and Acheloplasma laidlawii, and
      the viruses encephalomyocarditis virus and porcine enterovirus types 2 and 7 were
      isolated from individual pigs. An unknown agent however, was isolated from 16 of
      20 piglets and from 41 of 63 sows. This agent was characterized as a virus and
      designated Lelystad virus. No relationship between this virus and other viruses
      has yet been established. Of 165 sows reportedly affected by the disease, 123 (75
      per cent) seroconverted to Lelystad virus, whereas less than 10 per cent
      seroconverted to any of the other virus isolates or to known viral pathogens.
      Antibodies directed against Lelystad virus were also found in pigs with mystery
      swine disease in England, Germany, and the United States. We conclude that
      infection with Lelystad virus is the likely cause of mystery swine disease.

PMID- 10952440
TI  - The use of skin delayed-type hypersensitivity as an adjunct test to diagnose
      brucellosis in cattle: a review.
AB  - Brucellosis, caused by bacteria of the genus Brucella, is a contagious disease
      that causes economic loss to owners of domestic animals due to loss of progeny
      and milk yield. Because cattle, sheep, goats, and to a lesser extent pigs are
      considered to be the source of human brucellosis, serological tests have been
      used to screen domestic animals for antibodies against Brucella. Although the
      serological tests helped to eradicate brucellosis in many countries, serological
      tests are not always adequate to detect latent carriers of Brucella. Therefore,
      the use of the skin delayed-type hypersensitivity (SDTH) test, which is
      independent of circulating antibodies, might improve the diagnosis of
      brucellosis. In the literature, however, there are conflicting reports as to the
      value of the SDTH test for the diagnosis of brucellosis. Some studies consider
      the test unreliable, whereas others advocate its use because it detects
      brucellosis earlier than serological tests. The objectives of this study were
      therefore to assess the characteristics of the SDTH test, to select a Brucella
      strain that will yield a suitable brucellin for use in the field, and to
      determine whether the use of serological tests in combination with the SDTH test
      improves the detection of brucellosis. The results of this study clearly show
      that the SDTH test detects latent carriers of Brucella and confirms brucellosis
      in cattle with ambiguous serological test results. Brucellins prepared from
      smooth or mucoid strains of Brucella are better suited for use in the field than
      brucellins prepared from rough strains because they detect brucellosis in cattle
      with acute as well as chronic infection. The SDTH test is highly specific (99.3%
      specificity), and repeated testing of naive cattle or cattle infected with
      microorganisms that serologically cross-react with Brucella does not sensitize
      cattle to subsequent SDTH tests. However, it is possible that some naive cattle
      may serologically react to the injection of brucellin. The effect of these
      serological reactions on the sero-diagnosis of brucellosis is limited, because
      cattle may only now and then react serologically either with the serum
      agglutination test (SAT) or the complement fixation test (CFT). Nevertheless,
      cattle infected with microorganisms that serologically cross-react with Brucella
      may test seropositive for brucellosis 4 to 7 weeks after injection of brucellin,
      depending on the cross-reacting microorganism. The value of the SDTH test for the
      diagnosis of brucellosis was demonstrated after an outbreak of brucellosis. When
      the SDTH test was used in combination with SAT and CFT at diagnostic threshold >
      or =2 mm or > or =1 mm (increase in skinfold thickness), respectively, 39/44
      (88%) or 42/44 (95%) of the infected cattle were detected compared with only
      27/44 (61%) when SAT and CFT were used. When cattle in areas of low prevalence or
      in areas free from brucellosis are tested with the SDTH test an increase > or =2
      mm in skinfold thickness should be considered indicative of infection. When the
      control and eradication of brucellosis is based on test-and-slaughter, an
      increase of > or =1 mm in skinfold thickness should be considered indicative of
      infection. Repeated serological testing complemented with the SDTH test in this
      programme will shorten the quarantine (movement control) period of a suspect
      herd, limiting the financial loss incurred during outbreaks of the disease.
      Consequently, since the SDTH test usually does not interfere with the serological
      diagnosis and can safely be used to establish the infection status of cattle in a
      suspect herd, it is opportune to consider adding the SDTH test to the procedure
      currently used to diagnose brucellosis in individual animals.

PMID- 10952441
TI  - Field evaluation of efficacy and tolerance of a 2% marbofloxacin injectable
      solution for the treatment of respiratory disease in fattening pigs.
AB  - In a controlled and randomized field trial carried out in three European
      countries, 219 fattening pigs, from seven farms with respiratory disease
      problems, were treated intramuscularly for three or five days either with
      marbofloxacin 2 mg/kg/day, or with amoxicillin 7 mg/kg/day. Pigs were monitored
      daily until D5 (Day 5) and again at D21, and were weighed at D0 and D21.
      Pasteurella multocida, Actinobacillus pleuropneumoniae, and Mycoplasma
      hyopneumoniae were mainly identified in the pig lungs. The difference in the cure
      rate (74.5% in marbofloxacin group versus 68% in the amoxicillin group) was not
      significant. Mean rectal temperature was significantly lower after treatment with
      marbofloxacin. Other criteria tended to be favourable for the marbofloxacin
      group, although differences were not significant. The time to cure tended to be
      shorter for the marbofloxacin group (24.3% of pigs at 24 hours post-treatment
      versus 12.1% in the amoxicillin group). Marbofloxacin and amoxicillin relapse
      rates were 11.9% and 17.2% respectively (not significant) and daily weight gain
      was 746 g in the marbofloxacin group versus 687 g in the amoxicillin group (not
      significant). The 2% marbofloxacin solution was significantly better tolerated
      than amoxicillin.

PMID- 10952443
TI  - Primary and metastatic carcinomas in the digits of cats.
AB  - In the period 1993-1998, digital carcinomas in 64 cats were examined. In all
      animals primary complaints were painful digit(s). Eight cats had a primary
      squamous cell carcinoma which involved one digit or two adjacent digits of one
      leg. Fifty-six cats had metastases of a pulmonary carcinoma in the digits, and in
      general multiple digits of different legs were involved. In many of these cats
      metastases also occurred in other organs, including the skin and muscles. No
      primary sweat gland carcinomas of the digits were seen. Primary squamous cell
      carcinomas of the digits were characterized by cornification and the absence of
      PAS-positive cells, PAS-positive secretory material. Immunohistochemically, these
      neoplasms stained negative with the monoclonal antibody CAM 5.2 directed against
      Keratin 8 (K 8). The metastases of pulmonary carcinomas to the digits showed one
      or more of the following histological features: goblet cells, ciliated epithelial
      cells, PAS-positive cells or lakes, and/or a PAS-positive lining of luminal
      membranes and no cornification. Immunohistochemically, they showed positive
      staining for CAM 5.2 (K8). Thoracic radiographs from three cats with a primary
      squamous cell carcinoma showed no abnormalities, whereas all cases of metastases
      from a pulmonary carcinoma to the digits available for follow-up showed evidence
      of a primary pulmonary carcinoma on radiography and/or postmortem examination (25
      out of 56). The conclusion of this study was that most carcinomas in the digits
      of cats were metastases of a primary pulmonary carcinoma (87.5%). Primary
      squamous cell carcinomas occurred infrequently. The prognosis of metastases of a
      pulmonary carcinoma in the digits is poor with an average survival time of 4.9
      weeks, in contrast to 29.5 weeks in cats with a squamous cell carcinoma. These
      data stress the importance of taking thoracic radiographs of cats with digital
      tumours before surgical intervention.

PMID- 10952442
TI  - Time courses of plasma magnesium concentrations and urinary magnesium excretion
      in cows subjected to acute changes in potassium intake.
AB  - Hypomagnesaemic tetany in cows develops occasionally after an acute increase in K
      intake such as can occur when cows are transferred to spring grass. There is
      evidence that under these conditions plasma Mg concentrations are only
      transiently decreased. In this study the questions addressed were whether the
      plasma Mg concentration, indeed adapts to a high K intake as only dietary
      variable, and whether urinary Mg excretion is associated with this adaptation.
      Dry cows were fed rations containing either 26 or 50 g K/kg dm, the extra K being
      in the form of KHCO3. When the cows were acutely transferred from the low to the
      high K ration, plasma Mg concentrations fell slightly, but significantly from
      0.86 to 0.76 mmol/l within five days, but rose again to 0.80 mmol/l after another
      23 days, this rise being also statistically significant. None of the animals
      developed tetany. The decrease in plasma Mg concentration in individual animals
      after five days on the high-K ration ranged from 6 to 21%. The time course of
      urinary Mg excretion resembled that of plasma Mg concentration; minimum Mg
      excretion was seen after four to six days on the high-K ration with a subsequent
      increase thereafter. To explain the transient lowering of plasma Mg
      concentration, it is suggested that the K-induced decrease in Mg status caused a
      delayed increase in the carrier-mediated component of Mg absorption, which in
      turn caused an increase in urinary Mg excretion. When the cows were acutely
      switched from the high to the low K ration, plasma Mg concentration and urinary
      Mg excretion rose, but no transient changes were seen.

PMID- 10952444
TI  - Production performance and pruritic behaviour of pigs naturally infected by
      Sarcoptes scabiei var. suis in a contact transmission experiment.
AB  - Reports on the effects of mange on the production performance of pigs are
      conflicting. So far, studies have used experimental infections, by depositing
      encrusted lesions from chronically infected pigs into the ears of experimental
      pigs. However, this is a poor representation of what happens under natural field
      conditions. The purpose of our study was to quantify the effects of sarcoptic
      mange on production performance and pruritus in pigs that were infected by
      contact with S. scabiei var. suis-infected pigs. A total of 80 piglets were
      matched by sex and weight and randomly divided between experimental and control
      compartments. In the experimental compartment, each of three naturally S. scabiei
      var. suis-infested pigs were randomly allocated to three pens with 13 susceptible
      pigs each. From day 0 to 35, the growth performance of pigs in the experimental
      compartment was significantly (P=0.04) worse (35 g/d) than of pigs in the control
      compartment. From day 35 to 112, there was a statistical trend (P=0.10) that the
      growth performance of pigs in the experimental compartment was lower (50 g/d)
      than that of pigs in the control compartment. For the complete fattening period
      (0-112 or more days), the growth performance of pigs in the experimental
      compartment was significantly (P=0.05) worse (41 g/d) than that of pigs in the
      control compartment. Mean feed conversion ratio (kg feed per kg gain) was 2%
      higher in the experimental compartment compared with the control compartment.
      Pigs in the experimental compartment had a nine times (95% CI: 2 - 44) higher
      chance of showing pruritic behaviour than pigs in the control compartment.

PMID- 10952445
TI  - Prevention of transplacental transmission of moderate-virulent classical swine
      fever virus after single or double vaccination with an E2 subunit vaccine.
AB  - The use of a vaccine against classical swine fever virus (CSFV) during an
      outbreak of CSF should lead to a reduction in the horizontal or vertical
      transmission of CSFV. The reduction of vertical, i.e. transplacental,
      transmission of a moderate-virulent strain of CSFV from the sow to its offspring
      was studied in sows vaccinated once or twice with a CSFV E2 subunit vaccine. Two
      groups of nine sows were vaccinated with one PD95 dose of the E2 subunit vaccine,
      approximately four weeks before insemination. A third group of nine inseminated
      sows served as controls. One group of nine sows were vaccinated again at two
      weeks after insemination. At ten weeks after the primary vaccination,
      approximately six weeks after insemination, all 27 sows were challenged
      intranasally with 10(5) TCID50 of a moderate-virulent strain of CSFV, the Van
      Zoelen strain. The sows were euthanized at five weeks after challenge, and
      samples from the sows and fetuses were collected for detection of CSFV. All 27
      sows were in gestation at the time of slaughter, CSFV was detected in the fetuses
      of all unvaccinated sows but it was not detected in any of the samples collected
      from fetuses of the double-vaccinated sows. Virus was however recovered from the
      fetuses of one out of nine sows vaccinated once. All the sows, except four double
      vaccinated sows, developed CSFV Erns antibodies. Transplacental transmission of
      CSFV was reduced significantly (p <0.001) in all vaccinated sows. When the
      results from the experiment were extrapolated to a herd level, it could be
      concluded that, with 95% certainty, approximately 11% (single vaccination) or 0%
      (double vaccination), confidence intervals of 0.01-0.44 and 0.0-0.30
      respectively, of the pregnant sows would still not be protected against vertical
      transmission of moderate-virulent CSFV. We conclude that vaccination with the
      CSFV E2 subunit vaccine can reduce the transmission of moderate-virulent strain
      of CSFV from the sow to its offspring significantly.

PMID- 10952446
TI  - Fibrocartilaginous embolism of the spinal cord (FCE) in juvenile Irish
      Wolfhounds.
AB  - This study describes the occurrence of fibrocartilaginous embolism of the spinal
      cord (FCE) in eight juvenile Irish Wolfhounds that were presented within a period
      of 16 months (1996-1997). The dogs, seven males and one female between eight and
      13 weeks of age, were presented because of an acute onset of abnormal locomotion.
      Five dogs were euthanized and FCE was diagnosed by the histomorphological
      presence of focal myelomalacia and Alcian blue-positive-nucleus-pulposus material
      in the spinal cord vasculature. Three dogs, which were thought to have FCE
      because of their clinical symptoms, improved with partial or almost complete
      return to normal locomotion. Although the observed high incidence may be a
      coincidence, oral information from breeders and lay reports of similar cases in
      journals for dog breeders from various countries suggest that FCE is a common
      disorder in young Irish Wolfhounds.

PMID- 10952447
TI  - Prevention of pleuropneumonia in pigs by in-feed medication with
      sulphadimethoxine and sulphamethoxazole in combination with trimethoprim.
AB  - The prophylactic effect of in-feed medication of conventional pigs with
      sulphadimethoxine (SDM), sulphamethoxazole (SMX), and trimethoprim (TMP) was
      tested by using an Actinobacillus pleuropneumoniae infection model. In each of
      five experiments, six pigs were given medicated feed twice daily and three pigs
      received antibiotic-free feed and served as positive (unmedicated, infected)
      controls. The following drugs or drug combinations were tested (in mg per kg
      feed): 500 SDM + 100 TMP, 500 SMX + 100 TMP, 125 SMX + 25 TMP, 125 SMX (alone)
      and 25 TMP (alone). After six days of feed medication, all animals were
      endobronchially inoculated with A. pleuropneumoniae in a dose of 1-3.10(4) colony
      forming units (CFU). The response to the challenge in all control pigs was
      characterized by fever, lethargy, anorexia, reduced water consumption, and
      laboured breathing. At autopsy all controls manifested a fibrinous haemorrhagic
      pleuropneumonia. In-feed medication with 500 SDM + 100 TMP, 500 SMX + 100 TMP as
      well as 125 SMX + 25 TMP resulted in an effective protection against the
      challenge in all treated animals. After consumption of feed medicated with 125 mg
      per kg SMX or 25 mg per kg TMP, pleuropneumonia was evident in all challenged
      pigs. The results of this study indicate an in vivo potentiation of SMX and TMP
      in pigs against this respiratory tract pathogen.

PMID- 10952448
TI  - Characterization of Escherichia coli isolated from adult horses with and without
      enteritis.
AB  - In the present study E. coli strains isolated from the faeces of ten horses with
      diarrhoea and 14 horses without diarrhoea were characterized. All horses were
      culture negative for Salmonella species. Nine colonies of E. coli from each
      faecal sample were picked at random and a DNA fingerprint was made by means of a
      polymerase chain reaction (PCR) using Enterobacterial Repetitive Intergenic
      Consensus (ERIC) primers. The number of E. coli genotypes did not differ
      significantly between horses with and without diarrhoea. In addition, all E. coli
      strains with different DNA fingerprints were tested by PCR for genes encoding the
      virulence factors K88, F41, F17, CS31a, Sta1, LT1, VT2, CNF, BFP, and intimin.
      Genes coding for K88, F41, BFP, STa1, VT2, and CS31A were not detected. Genes for
      CNF were found in strains from one horse with diarrhoea and one horse with normal
      faeces. Genes for LT1 (n=1) and intimin (n=1) were found only in strains from
      horses with normal faeces. Genes for F17 fimbriae were found in strains from
      three horses with diarrhoea (30%) and in none of the strains from healthy horses.
      In two of these horses, E. coli strains with different DNA polymorphism patterns
      were F17 positive; however, none of these strains possessed LT1, Sta1, or CNF
      genes. Haemolytic E. coli strains were only isolated from two horses with
      diarrhoea and from none of the healthy horses. Nineteen percent of all E. coli
      strains did not ferment lactose. Eight per cent of these lactose-negative strains
      were from horses with diarrhoea, whereas 32% were from horses without diarrhoea.
      In conclusion, virulence factors were present in E. coli isolates from horses
      with and without diarrhoea, except for F17, which was only found in E. coli
      isolated from horses with diarrhoea. F17-positive E. coli might have importance
      as cause of diarrhoea in horses, but further studies are needed.

PMID- 10952449
TI  - Isolation and characterization of porcine circovirus type 2 from pigs showing
      signs of post-weaning multisystemic wasting syndrome in The Netherlands.
AB  - Pigs with wasting syndrome were examined for macroscopic and histopathological
      lesions, and for porcine circovirus (PCV). Histopathological lesions were
      comparable to those previously documented for post-weaning multisystemic wasting
      syndrome (PMWS). In addition, in seven out of ten examined PMWS-affected pigs
      focal-to-slight mononuclear meningitis and focal cerebral mononuclear infiltrates
      (4 out of 10) were observed. A virus was isolated from organs and sera from pigs
      showing wasting syndrome. An immunoperoxidase monolayer assay and an indirect
      immunofluorescence assay were performed on the infected PK-15 and Dulac cell
      cultures, respectively, and both assays indicated the presence of PCV type 2
      (PCV2). The nested-polymerase chain reaction (nPCR) technique, based on the use
      of PCV2 specific oligonucleotides, revealed specific amplified products of 481
      bp. Nucleotide sequence analysis of the entire genome of the Dutch PCV isolate
      24657 NL showed a homology with known nucleotide sequences of porcine PCV type 1
      (PCV1) and PCV2 isolates of 77.1% and >96%, respectively. This is the first
      report of the isolation and characterization of PCV2 in PMWS-affected pigs in the
      Netherlands.

PMID- 10952450
TI  - Cerebellar cortical abiotrophy in two Portuguese Podenco littermates.
AB  - Cerebellar cortical abiotrophy in two Portuguese Podenco littermates is reported
      and discussed. The disease is characterized by progressive cerebellar ataxia with
      an early onset of two to three weeks. Extensive loss, degeneration, and necrosis
      of Purkinje cells particularly involved the cerebellar hemispheres. An autosomal
      recessive pattern of inheritance is suspected.

PMID- 10952451
TI  - Using serum amyloid A to screen dairy cows for sub-clinical inflammation.
AB  - In this study, 232 lactating dairy cows from six herds were observed for clinical
      signs of inflammation and simultaneously had blood samples drawn to determine
      whether or not Serum Amyloid A (SAA) was present. Serum protein electrophoresis
      and white blood cell differential count revealed inflammation in SAA+ samples but
      not in SAA-samples. Using positive SAA test results as the standard for presence
      of inflammation, clinical findings consistent with inflammation concurred with
      positive SAA results only 26% of the time (p<.001) while the lack of clinical
      signs consistent with inflammation concurred with negative SAA results 95% of the
      time (p<.001). There was also a significant difference (p<.005) in management
      styles in that cows permanently fed on wilted/cured forages and kept inside had a
      26% prevalence of positive SAA blood samples whereas the overall prevalence of
      SAA+ samples was 16%. These findings indicate that whole herd screening using SAA
      can be of value to the veterinarian in helping to identify cows with inflammatory
      diseases. From a public health perspective, SAA testing of cows going to market
      can help differentiate those not needing intensive inspection from those that do.

PMID- 10952452
TI  - The effect of intravenous medetomidine on pupil size and intraocular pressure in
      normotensive dogs.
AB  - Medetomidine, a highly specific alpha-2 adrenergic agonist, has been demonstrated
      to lower intraocular pressure (IOP) in rabbits and cats when applied topically.
      The purpose of this study was to assess the influence of intravenously injected
      medetomidine on the pupil size (PS) and the IOP of non glaucomatous dogs. IOP was
      measured by applanation tonometry and PS was measured using Jameson calipers at
      t=0 (or time of IV injection of medetomidine (Domitor; Orion) at the dose of 1500
      microg/m2 body surface area) and again after 5 minutes (t=5). The IV
      administration of medetomidine caused miosis in all 14 dogs. The mean PS
      decreased from 9.0 to 4.0 mm (p<0.001). The IOP was lowered in 10 dogs and in 4
      dogs there was a rise in IOP. The mean IOP (mmHg) decreased from 22 to 21
      (p>0.2). The data presented above confirm that medetomidine at a dose of 1500
      microg/m2 body surface area produces miosis in non glaucomatous dogs, without
      influencing the IOP.

PMID- 10952453
TI  - Insulin action and insulin resistance in human skeletal muscle.

PMID- 10952454
TI  - Measuring clinical performance and outcomes from diabetes information systems: an
      observational study.
AB  - AIMS/HYPOTHESIS: To examine changes in diabetes care provision after the
      introduction of a district diabetes information system. METHODS: All patients
      with diabetes registered on the system between 1993 and 1998 (n = 6544) were
      included in the analysis. Drop-out cohort analysis was used to handle population
      changes, logistic regression models with general estimating equations were used
      to examine changes in clinical performance over time. RESULTS: After the
      introduction of the system, care processes improved appreciably, in both primary
      and secondary care. The proportion of patients receiving a preventative care
      review within the calendar year rose from 56% in 1993 to 67% in 1998. The
      proportion of these in whom each process was completed improved in all categories
      from 1993 to 1998: blood pressure 96% to 98%; glycaemic check 67% to 93%; lipid
      check 31% to 68%; renal check 46% to 87%; fundoscopy 79% to 92%; foot screen 87%
      to 87%. Similarly there was an increase in the proportion of patients achieving
      intermediate outcome treatment targets (HbA1c < or = 9.0% from 29% to 43%;
      cholesterol < or = 5.5 mmol/1 5% to 19%; blood pressure < or = 160/90 37% to
      46%). CONCLUSION/INTERPRETATION: Our results suggest appreciable improvements in
      diabetes care between 1993 and 1998. These changes apply to an entire population
      of patients across primary and shared care. We believe that these improvements
      could, in part, be attributable to the way in which the district diabetes
      information system has facilitated the structured cascade of diabetes care.

PMID- 10952455
TI  - Decreasing incidence of major amputations in people with diabetes.
AB  - AIMS/HYPOTHESIS: To assess the results of the strategy used in avoiding major
      amputations in patients with diabetes mellitus. METHODS: A retrospective study
      for the years 1981 to 1995 in a central district hospital in Copenhagen with a
      catchment area population of about 178,000. RESULTS: There were 463 major leg
      amputations and the incidence decreased from 27.2 to 6.9/100,000 population
      (75%). The decrease in patients with Type I (insulin-dependent) diabetes mellitus
      was from 10.0 to 4.1 (59%) and in Type II (non-insulin-dependent) diabetes
      mellitus from 17.2 to 2.8/100,000 people (84%). Analysis showed that the diabetic
      population remained constant despite a considerable fall in the number of older
      people. During the study period infra-popliteal arterial bypass was introduced
      for the treatment of critical lower limb ischaemia and in diabetic patients the
      number of bypasses increased from zero to 13/100,000 population. The total number
      of revascularisation procedures in people with diabetes increased from 2.6 to
      19.2/100,000 population. Moreover, a multidisciplinary diabetic foot clinic was
      established. CONCLUSION/INTERPRETATION: A 75% reduction in the incidence of major
      amputations coincided with a sevenfold increase in revascularization procedures
      and the establishment of a multidisciplinary diabetic foot clinic suggesting
      these measures are important in the prevention of diabetic leg amputations.

PMID- 10952456
TI  - Short stature and gestational diabetes in Brazil. Brazilian Gestational Diabetes
      Study Group.
AB  - AIMS/HYPOTHESIS: To examine the association between maternal stature and
      gestational diabetes mellitus. METHODS: We studied a sample of 5564 consecutive
      Brazilian women 20 or more years old, who were pregnant for approximately 21-28
      weeks, had no history of diabetes outside pregnancy and were attending general
      prenatal care units in six state capitals in Brazil from 1991 to 1995. We did a 2
      h, 75-g oral glucose tolerance test, defining gestational diabetes by World
      Health Organisation criteria. RESULTS: Those in the shortest quartile of height
      (< or = 151 cm) had a 60% increase in the odds of having gestational diabetes,
      independently of prenatal clinic, age, global obesity, family history of
      diabetes, skin colour, referral pattern, waist circumference, parity, previous
      gestational diabetes, education, ambient temperature and gestational age compared
      with the tallest quartile [odds ratio (OR) = 1.60, p = 0.005]. This association
      was observed for those with above median values of skinfold thickness (OR = 1.74,
      p = 0.006) but not for those with below median values (OR = 1.22, p = 0.51).
      Associations of short stature with high 2-h glycaemia (> or = 7.8 mmol/l) (OR =
      1.61, p = 0.005) were essentially the same as those for gestational diabetes.
      There was, however, no association between short stature and gestational
      hyperglycaemia when the latter was defined exclusively by fasting values (OR =
      0.97, p = 0.90). CONCLUSION/INTERPRETATION: In Brazil short stature associates
      with gestational diabetes, principally in women with greater fat mass. This
      difference in glycaemic levels is present postprandially but not in the fasting
      state.

PMID- 10952457
TI  - Characterisation of beta-cell dysfunction of impaired glucose tolerance: evidence
      for impairment of incretin-induced insulin secretion.
AB  - AIMS/HYPOTHESIS: Our studies were undertaken to characterise the defective
      insulin secretion of impaired glucose tolerance (IGT). METHODS: We studied 13
      normal glucose tolerant subjects (NGT) and 12 subjects with IGT carefully matched
      for age, sex, BMI and waist-to-hip ratio. A modified hyperglycaemic clamp (10
      mmol/1) with a standard 2-h square-wave hyperglycaemia, an additional glucagon
      like-peptide (GLP)-1 phase (1.5 pmol x kg(-1) x min(-1) over 80 min) and a final
      arginine bolus (5 g) was used to assess various phases of insulin secretion rate.
      RESULTS: Insulin sensitivity during the second phase of the hyperglycaemic clamp
      was low in both groups but not significantly different (0.12 +/- 0.021 in NGT vs
      0.11 +/- 0.013 micromol x kg(-1) x min(-1) x pmol(-1) in IGT, p = 0.61). First
      phase insulin secretion was lower in IGT (1467 +/- 252 vs 3198 +/- 527 pmol x
      min(-1), p = 0.008) whereas the second phase was not (677 +/- 61 vs 878 +/- 117
      pmol x min(-1), p = 0.15). The acute insulin secretory peak in response to GLP-1
      was absent in IGT subjects who only produced a late phase of GLP-1-induced
      insulin secretion rate which was lower (2228 +/- 188 pmol x min(-l)) than in NGT
      subjects (3056 +/- 327 pmol x min(-1), p = 0.043). Insulin secretion in response
      to arginine was considerably although not significantly lower in IGT subjects.
      The relative impairment (per cent of the mean rate for NGT subjects) was greatest
      for the GLP-1 peak (19 +/- 9%). CONCLUSION/INTERPRETATION: In this Caucasian
      cohort a defective insulin secretion rate is essential for the development of
      IGT. The variable degrees of impairment of different phases of the insulin
      secretion rate indicate that several defects contribute to its abnormality in
      IGT. Defects in the incretin signalling pathway of the beta cell could contribute
      to the pathogenesis of beta-cell dysfunction of IGT and thus Type II (non-insulin
      dependent) diabetes mellitus.

PMID- 10952458
TI  - Interaction between adrenal glucocorticoids and parasympathetic activation in
      mediating hyperinsulinaemia during long-term central neuropeptide Y infusion in
      rats.
AB  - AIMS/HYPOTHESIS: Hypothalamic neuropeptide Y is implicated in the aetiology of
      obesity and insulin resistance because of its hyperinsulinaemic, hyperphagic
      effects. We investigated the interaction of adrenal glucocorticoids and the
      parasympathetic nervous system in the hyperinsulinaemia caused by neuropeptide Y
      infusion in rats. METHODS: Neuropeptide Y was intracerebroventricularly given to
      normal or adrenalectomised rats for 3-6 days with pair-feeding, with or without
      subcutaneous dexamethasone infusion. We measured basal and intravenous glucose
      induced insulinaemia and the effect of prior atropine injection. RESULTS:
      Neuropeptide Y increased basal plasma insulin and C-peptide concentrations (380
      +/- 90 and 1000 +/- 60 pmol/1, vs 190 +/- 20 and 590 +/- 50 pmol/1 in controls, p
      < 0.05). Neuropeptide Y also increased the plasma concentrations of these
      hormones as early as 60 s after glucose injection (1630 +/- 170 and 3200 +/- 170
      pmol/1 for insulin and C peptide, respectively, vs 1080 +/- 80 and 1860 +/- 130
      pmol/1 in controls, p < 0.05). Atropine reversed the effect of neuropeptide Y on
      basal plasma insulin and C-peptide concentrations but had no effect on post
      glucose plasma concentrations. The hyperinsulinaemic effects of neuropeptide Y
      were prevented by adrenalectomy, but were restored by dexamethasone infusion.
      Dexamethasone in itself did not statistically significantly increase insulinaemia
      in adrenalectomised rats. As in intact rats, atropine attenuated the basal
      hyperinsulinaemia of adrenalectomised rats that had been infused with
      neuropeptide Y and dexamethasone but had no effect on post-glucose
      hyperinsulinaemia. CONCLUSION/INTERPRETATION: These data suggest firstly that
      neuropeptide Y infused centrally induces basal hyperinsulinaemia in rats through
      glucocorticoid-dependent parasympathetic activation to the pancreas. Secondly,
      neuropeptide Y potentiates glucose-induced insulinaemia through a pathway
      dependent on adrenal glucocorticoids that cannot be reversed by short-term
      blockade of the increased parasympathetic tonus.

PMID- 10952459
TI  - Abnormal insulin and beta-adrenergic modulation of lipoprotein liipase during
      refeeding after prolonged fasting in the Zucker rat.
AB  - AIMS/HYPOTHESIS: To characterise the response of tissue lipoprotein lipase to
      refeeding after prolonged (24 h) fasting in lean and obese Zucker rats, and to
      verify whether lipoprotein lipase in obese rats is resistant to the short-term
      action of insulin and escapes modulation by the beta-adrenergic pathway. METHODS:
      Lean Fa/? and obese fa/fa male Zucker rats fasted for 24 h and refed at will.
      Lipoprotein lipase activity in adipose and muscle tissues was assessed in the
      freely fed and fasted states and at various times during refeeding, with or
      without beta-adrenergic blockade (propranolol). RESULTS: The 24 h fast erased the
      phenotype-related differences in insulinaemia and adipose lipoprotein lipase
      activity present in freely fed rats. Adipose lipoprotein lipase increased twofold
      in obese rats 1 h after refeeding, whereas no change occurred at that time in
      lean rats. Activity remained at that level for at least 6 h after refeeding in
      obese rats, whereas in lean animals it was increased fivefold after 6 h of
      refeeding. In muscle of obese rats, lipoprotein lipase decreased in response to
      refeeding, but paradoxically increased twofold in lean animals. Giving
      propranolol to lean rats before refeeding abolished the atypical response of
      muscle lipoprotein lipase to food intake and restored the early (1 h after
      refeeding) increase in adipose lipoprotein lipase but had no effect in obese
      rats. CONCLUSION/INTERPRETATION: Refeeding after prolonged fasting activates the
      P-adrenergic pathway in lean rats, which transiently counteracts insulin-mediated
      modulation of lipoprotein lipase. The P-adrenergic pathway is not activated by
      refeeding in adipose tissue and muscle of the obese Zucker rat. In the obese
      Zucker rat, the early modulation of adipose lipoprotein lipase activity is
      abnormal upon refeeding after prolonged fasting, suggesting short-term resistance
      to the action of insulin.

PMID- 10952460
TI  - The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and
      insulin resistance in rats fed a high-fat diet.
AB  - AIMS/HYPOTHESIS: Fat balance is critical in the aetiology of obesity and related
      diseases. Lipoprotein lipase is of major importance in lipid metabolism. The aim
      of this study was to investigate the long-term effects of the lipoprotein lipase
      activator, NO-1886, on substrate utilisation, adiposity and insulin action in
      rats fed a high-fat diet. METHODS: Male, Sprague-Dawley rats were fed for 10
      weeks on a chow diet or a high-fat diet with, or without, NO-1886 (50 mg x kg(-1)
      x day(-1)). Weight gain, fat accumulation and both hormone-sensitive and
      lipoprotein, lipase activities were measured. Insulin action was assessed by the
      euglycaemic hyperinsulinaemic clamp and metabolic rate/substrate utilisation by
      open-circuit respirometry. RESULTS: Compared with chow-fed controls, a high-fat
      diet increased weight gain, an effect lessened by NO-1886 [weight gain (g): chow,
      37 +/- 3, high-fat, 222 +/- 9; high-fat + NO-1886, 109 +/- 6, all groups differed
      p < 0.001]. A similar pattern existed for fat accumulation [visceral fat (g):
      chow, 35.9 +/- 3.2; high-fat, 81.9 +/- 6.6; high-fat + NO-1886, 52.3 +/- 4.7, p <
      0.01 high-fat vs the other groups]. A high-fat diet induced wholebody insulin
      resistance (clamp glucose infusion rate: 4.8 +/- 1.3 mg x kg(-1) x min(-1) vs
      10.6 +/- 1.1 for the chow group, p < 0.01) with NO-1886 lessening this effect
      (8.3 +/- 0.5, p < 0.05 vs high-fat). The 24-h respiratory quotient was lower in
      the high-fat + NO-1886 group (0.825 +/- 0.010) compared with high-fat alone
      (0.849 +/- 0.004, p < 0.05). A high-fat diet increased lipoprotein and hormone
      sensitive, lipase activities in epididymal fat, an effect not altered by NO-1886.
      In myocardium and skeletal muscle a high-fat diet lowered lipoprotein lipase
      activity, an effect lessened by NO-1886. CONCLUSION/INTERPRETATION: Lipoprotein
      lipase activators could have potential benefits for the treatment of obesity by
      increasing fat utilisation.

PMID- 10952461
TI  - Two amino acids in glutamic acid decarboxylase act in concert for maintenance of
      conformational determinants recognised by Type I diabetic autoantibodies.
AB  - AIMS/HYPOTHESIS: Glutamic acid decarboxylase 65 is a major autoantigen in Type I
      (insulin-dependent) diabetes mellitus, autoimmune polyendocrine syndrome and
      stiff-man syndrome. These disorders are characterised by the presence of multiple
      autoantibodies to the autoantigen which can be distinguished in a variety of
      different ways. We have investigated the role of single amino-acid mutations in
      glutamic acid decarboxylase 65 in distinguishing the binding of serum antibodies
      and a variety of patient-derived human IgG monoclonal antibodies directed to
      different determinants of the autoantigen. METHODS: We identified a mutant of
      glutamic acid decarboxylase 65 that contained four single amino-acid mutations
      from the wild-type molecule. The role of these mutations was investigated by site
      directed mutagenesis. We investigated the binding of patient-derived serum
      antibodies to glutamic acid decarboxylase 65 to a number of single and double
      amino-acid mutants using immunoprecipitation with labelled, recombinant antigen.
      To overcome the heterogeneity of different anti-glutamic acid decarboxylase 65
      antibodies present in a patient's serum, the binding of a panel of eleven patient
      derived human monoclonal antibodies recognising different determinants on the
      autoantigen was also studied. RESULTS: Two replacements in glutamic acid
      decarboxylase 65 at Asn247Ser and Leu574Pro were identified that preferentially
      influence the anti-glutamic acid decarboxylase 65 serum antibodies of Type I
      diabetic patients, without statistically significantly effecting those recognised
      in other disorders. Single or double amino-acid replacements Asn247Ser and
      Leu574Pro in the autoantigen showed differential affects on expression of
      epitopes recognised by the human monoclonals. The double replacement of Asn247Ser
      and Leu574Pro in glutamic acid decarboxylase 65 resulted in the loss of binding
      of all eleven human monoclonal antibodies, irrespective of their epitope
      recognition. In contrast, single replacement of Leu574Pro statistically
      significantly reduced the binding of some carboxyl terminal-directed antibodies
      such as MICA 1, MICA 3 and DP-A without influencing the binding of other
      monoclonals. Replacement of Asn247Ser did not, however, influence the binding of
      any patients serum or human monoclonal antibodies. CONCLUSION/INTERPRETATION: Two
      distantly spaced amino acids, Asn247 and Leu574 in glutamic acid decarboxylase 65
      were identified that act in concert to greatly influence the conformational
      structure of the autoantigen and statistically significantly influence the
      binding of antibodies present in Type I diabetic sera. The single or double amino
      acid mutants can be used to distinguish some anti-glutamic acid decarboxylase-65
      autoantibodies and could prove useful in distinguishing Type I diabetic from
      autoimmune polyendocrine syndrome and stiff-man syndrome patients' sera as well
      as to study changes in antibody patterns during disease progression.

PMID- 10952462
TI  - Susceptibility to diabetes is widely distributed in normal class IIu haplotype
      rats.
AB  - AIMS/HYPOTHESIS: We did experiments to explore the pathways putatively leading to
      Type I (insulin-dependent) diabetes mellitus, and their association with the MHC
      locus, the major genetic determinant of disease susceptibility. METHODS: Normal
      MHC congenic rat strains that do not spontaneously develop diabetes or any other
      autoimmune syndrome were injected with the interferon-alpha inducer polyinosinic
      polycytidylic acid (Poly IC). RESULTS: Insulitis and diabetes developed only in
      strains expressing Class II(u) genes and was independent of the Class I
      haplotype. Poly IC induced islet cell Class I hyperexpression, up regulation of
      pancreatic endothelial intercellular adhesion molecule-1 and vascular adhesion
      molecule-1 and a T-cell and macrophage infiltration of the pancreatic
      interstitium in all rat strains studied, including diabetes-resistant strains.
      Poly IC also induced the generation of diabetes-transferring spleen cells in most
      Class II(u) haplotype rats, including the diabetes-resistant WF rat.
      CONCLUSION/INTERPRETATION: The minimum requirements for autoimmune diabetes
      development in the rat include: RT1 Class II(u) genes, a T-cell repertoire
      containing beta-cell autoreactive T cells and a triggering event which breaks
      tolerance by the local up regulation of pancreatic endothelial adhesion
      receptors. Even when all of the minimum requirements have, however, been met,
      most Class II(u) rats do not develop diabetes in response to autoimmune stimuli.
      It is clear, nonetheless, that susceptibility to diabetes is widely distributed
      in the RT1(u) rat.

PMID- 10952463
TI  - Transgenic mice overexpressing alpha2A-adrenoceptors in pancreatic beta-cells
      show altered regulation of glucose homeostasis.
AB  - AIMS/HYPOTHESIS: To study the role of the human alpha2A-adrenoceptor in the
      regulation of insulin secretion and the maintenance of glucose homeostasis in
      transgenic mice overexpressing this receptor in pancreatic beta cells. METHODS: A
      human insulin promoter/human alpha2C10-adrenoceptor chimeric gene was
      microinjected into mouse embryos and transgenic mice were obtained. RESULTS:
      Analysis by RT-PCR showed that the expression of the transgene was restricted to
      pancreatic islets. Study of the binding of the alpha2-antagonist [3H]RX821002 to
      membrane preparations showed that islets from transgenic mice had ninefold higher
      alpha2-adrenoceptor density than those from controls. Immunohistological analysis
      showed, however, no change in the number or size of islets between control and
      transgenic mice. Transgenic animals had normal glycaemia and insulinaemia in
      basal conditions but greater hyperglycaemic and hypoinsulinaemic responses after
      injection of the alpha2-agonist, UK14304. The lower blood insulin concentration
      detected in transgenic mice was a reflection of a stronger inhibitory effect of
      the alpha2-agonist on glucose-stimulated insulin secretion in transgenic islets
      than in controls. Furthermore, transgenic mice did not have lower glycaemia to
      basal values after an intraperitoneal glucose tolerance test. This defect was
      abolished by treatment with the alpha2-adrenoceptor antagonist, RX821002.
      CONCLUSION/INTERPRETATION: These results provide evidence in vivo that
      overexpression of alpha2-adrenoceptors in beta cells can lead to impaired insulin
      secretion and glucose intolerance.

PMID- 10952464
TI  - Modulation of rat pancreatic acinoductal transdifferentiation and expression of
      PDX-1 in vitro.
AB  - AIMS/HYPOTHESIS: In adult pancreatic regeneration models exocrine acini are found
      to transdifferentiate to duct-like complexes. This has also been associated with
      the formation of new endocrine islet cells. We aimed to establish an in vitro
      model in which this transdifferentiation process is characterised and can be
      modulated. METHODS: Purified rat pancreatic acini were cultured in suspension.
      Differentiation was analysed by immunocytochemistry, electron microscopy, western
      blotting and RT-PCR. RESULTS: During culture acinar cells directly
      transdifferentiated without dividing, the cells lost their acinar phenotype and
      started to express cytokeratins 20 and 7 and fetal liver kinase-1 (Flk-1)
      receptors for vascular endothelial growth factor. Expression of the acinar
      pancreatic exocrine transcription factor (PTF-1) remained and the pancreatic
      duodenal homeobox-containing transcription factor (PDX-1) was induced. When
      transdifferentiation was completed, the cells started to express protein gene
      product 9.5, a panneuroendocrine marker. By combining these features, the
      transdifferentiated cells show similar characteristics to precursor cells during
      active beta-cell neogenesis. We were able to modulate the differentiation state
      by addition of nicotinamide or sodium butyrate, agents which are known to
      stimulate endocrine differentiation in other models. CONCLUSION/INTERPRETATION:
      Here, we present an in vitro system in which the cellular differentiation of
      putative pancreatic endocrine precursor cells and their PDX-1 expression can be
      modulated, thereby providing a possible model for the study of beta-cell
      transdifferentiation.

PMID- 10952465
TI  - F-wave latency serves as the most reproducible measure in nerve conduction
      studies of diabetic polyneuropathy: multicentre analysis in healthy subjects and
      patients with diabetic polyneuropathy.
AB  - AIMS/HYPOTHESIS: For use in future drug development for diabetic polyneuropathy,
      we conducted multicentre trials to assess the reproducibility of nerve conduction
      studies. METHODS: All measurements were repeated twice at a time interval of 1-4
      weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with diabetic
      polyneuropathy. Using a standardised method, 32 centres participated in the study
      of control subjects and 65, in patients with diabetic polyneuropathy. Motor nerve
      conduction studies consisted of stimulating the left median and tibial nerves and
      recording the compound action potential from abductor policis and adductor
      hallucis for measuring amplitude, terminal latency and minimal F-wave latency.
      For sensory conduction studies, sensory nerve action potentials were recorded
      antidromically from the second digit and the posterior aspect of the lateral
      malleous after distal stimulation of the left median and sural nerves. We also
      calculated motor conduction velocity, F-wave conduction velocity and sensory
      conduction velocity. The relative intertrial variation and intraclass correlation
      coefficient were used as an index of reproducibility. RESULTS: Of all the
      measurements, F-wave latency yielded the highest intraclass correlation
      coefficient with the smallest relative intertrial variation for both median and
      tibial nerves in both groups. CONCLUSION/INTERPRETATION: Median and tibial F-wave
      latency provide the most reproducible measures for a nerve conduction study,
      serving as one of the best measures in multicentre drug trials for diabetic
      polyneuropathies.

PMID- 10952466
TI  - Role of insulin-like growth factor (IGF)-1 in the modulation of renal
      haemodynamics in Type I diabetic patients.
AB  - AIMS/HYPOTHESIS: We investigated in normotensive Type I (insulin-dependent)
      diabetic patients with normoalbuminuria the role of growth hormone-induced IGF-1
      in the modulation of renal haemodynamics. METHODS: We measured glomerular
      filtration (GFR) and renal plasma flow (RPF) at baseline and at 24 h after
      injection of different doses of growth hormone (0.1, 0.2, 0.4 U x kg(-1) x body
      weight(-1) in six patients with normal GFR under a euglycaemic clamp. We also
      examined a 24 h profile of plasma growth hormone and IGF-1 during usual insulin
      therapy in two other groups each with seven patients with a lower (from 93 to 114
      ml x min(-1) x (1.73 m2)(-1) and higher (from 121 to 146 ml min(-1) x (1.73 m2)(
      1) GFR. RESULTS: Plasma growth hormone concentrations peaked 2 h after its
      injection and plasma concentrations of IGF-1 peaked about 24 h after the growth
      hormone injection. There was a significant increase in GFR and RPF 24 h after the
      highest dose of the growth hormone injection (corresponding to the highest IGF-1
      concentration), from baseline values of 115 +/- 24 and 536 +/- 141 ml x min(-1) x
      (1.73 m2)(-1) to 160 +/- 33 and 657 +/- 137 ml x min(-1) x (1.73 m2)(-1),
      respectively (p < 0.01 for GFR and p < 0.05 for RPF). No differences were
      observed in the 24 h profile of growth hormone and IGF-1 plasma concentrations
      between the two groups; growth hormone and IGF-1 concentrations were lower than
      those obtained after the injection of 0.4 U x kg(-1) x body weight(-1) of growth
      hormone. CONCLUSION/INTERPRETATION: These results show that pharmacological
      growth hormone-induced IGF-1 concentrations are required to modify renal
      haemodynamics in Type I diabetic patients and suggest that, under the
      "physiological" conditions of diabetes, IGF-1 has no role as a mediator of
      glomerular hyperfiltration.

PMID- 10952467
TI  - Urinary albumin excretion and 24-hour blood pressure as predictors of pre
      eclampsia in Type I diabetes.
AB  - AIMS/HYPOTHESIS: To evaluate the value of 24-h blood pressure monitoring compared
      to office blood pressure and urinary albumin excretion in predicting pre
      eclampsia in Type I (insulin-dependent) diabetes mellitus. METHODS: The study
      included 136 consecutive pregnancies in Caucasian women with Type I diabetes
      before gestation without diabetic nephropathy, anamnestic hypertension or early
      abortion. Values of urinary albumin excretion and office blood pressure before
      pregnancy and the HbA1C value at the time of conception were obtained.
      Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/24 h in
      two out of three consecutive urine samples. Single measurements of 24-h urinary
      albumin excretion, office blood pressure and HbA1C were done five 5 times during
      pregnancy. In a subgroup of 74 women 24-h blood pressure measurements were done
      at 10 and 28 weeks of gestation. Pre-eclampsia was defined as office blood
      pressure higher than 140/90 mmHg accompanied by proteinuria above 0.3 g/24 h
      later than 20 weeks of gestation. RESULTS: Urinary albumin excretion and systolic
      blood pressure were higher before and throughout pregnancy in 14 women developing
      pre-eclampsia compared with women remaining normotensive (p <0.001; p < 0.05,
      respectively). By logistic regression analysis the best predictor for pre
      eclampsia was microalbuminuria before pregnancy (p < 0.05) with no additive
      predictive effect of 24-h blood pressure or office blood pressure measurement.
      The night:day ratio of blood pressure was similar in the two groups.
      CONCLUSION/INTERPRETATION: Microalbuminuria before pregnancy is the strongest
      predictor of pre-eclampsia in Type I diabetes. Measuring 24-h blood pressure
      early in pregnancy did not improve the ability to identify women at risk.

PMID- 10952468
TI  - Age-dependent changes in phenotypes and candidate gene analysis in a polygenic
      animal model of Type II diabetes mellitus; NSY mouse.
AB  - AIMS/HYPOTHESIS: The Nagoya-Shibata-Yasuda (NSY) mouse closely mimics human Type
      II (non-insulin-dependent) diabetes mellitus in that the onset is age-dependent,
      the animals are not severely obese, and both insulin resistance and impaired
      insulin response to glucose contribute to disease development. The aim of this
      study was to clarify the influence of age on the pathogenesis of diabetes and to
      analyse a candidate gene for Type II diabetes in this strain. METHODS: Several
      phenotypic characteristics related to diabetes mellitus were monitored
      longitudinally in male NSY and control C3H/He mice. The nucleotide sequence of
      Glut4, a candidate gene for Nidd1nsy (a susceptibility gene for Type II diabetes)
      on Chromosome 11, encoding insulin-sensitive glucose transporter, was determined
      in NSY and C3H mice. RESULTS: Glucose intolerance worsened with age, and fasting
      blood glucose and fasting plasma insulin concentration increased with age in NSY
      mice. Pancreatic insulin content increased until 24 weeks of age but then
      decreased at 48 weeks of age in NSY mice. The hypoglycaemic response to insulin
      was statistically significantly smaller in NSY than in C3H/He mice. The
      nucleotide sequence of GLUT4 cDNA was identical in NSY and C3H/He mice, but both
      were different from the sequence reported previously. CONCLUSION/INTERPRETATION:
      Insulin secretion and insulin resistance, as well as ageing possibly play an
      important part in the disease development in NSY mice. A decline of pancreatic
      insulin content in older age might cause the relative insulin deficiency in this
      strain. Nucleotide sequencing suggests that Glut4 is unlikely to be a candidate
      gene for Nidd1nsy.

PMID- 10952469
TI  - Growth characteristics of diabetic rat ectoplacental cones in vivo and in vitro.
AB  - AIMS/HYPOTHESIS: To investigate the outgrowth of the ectoplacental cone in
      diabetic rats in vivo and in vitro. METHODS: Female Wistar rats were injected
      intraperitoneally with streptozotocin (75 mg/kg body weight, n = 15), or with
      control buffer (n = 27) 3 days before mating. On day 9 (day 1 = copulation plug)
      decidual swellings were weighed and the volume and mitotic index of the embryo
      and ectoplacental cone were estimated. Also, ectoplacental cones were cultured
      either in the presence of decidual cells from pseudopregnant diabetic rats or in
      high glucose concentration media. Cultures were evaluated by the daily outgrowth
      and by the proportion of giant cells and proliferating cells on day 5. RESULTS:
      In diabetic rats on day 9, the weight of the decidual swellings and the mitotic
      index in the ectoplacental cone were lower compared with controls (p < 0.0001 and
      p < 0.05, respectively). In vitro, control ectoplacental cones in the presence of
      decidual cells from diabetic rats showed a slight reduction in outgrowth on day 3
      and 5 of culture. Outgrowth of diabetic ectoplacental cones in high glucose
      concentration medium was impaired on day 1 (p < 0.0005) compared with control
      ectoplacental cones in control medium, and on day 1 and 2 (both p < 0.005)
      compared with control ectoplacental cones in high glucose concentration medium.
      In control medium, the outgrowth of diabetic ectoplacental cones was impaired on
      day 1 (p < 0.05), compared with control ectoplacental cones. Proliferation was
      stimulated in diabetic ectoplacental cone cultures. CONCLUSION/INTERPRETATION:
      These data suggest that the outgrowth of diabetic ectoplacental cones is impaired
      by high glucose concentrations.

PMID- 10952471
TI  - Increased frequency of the lipoprotein lipase 9N allele in adults with Type I
      (insulin-dependent) diabetes mellitus.

PMID- 10952470
TI  - Non-esterified fatty acids and the liver: why is insulin secreted into the portal
      vein?
AB  - AIMS/HYPOTHESIS: Insulin control of glucose output is a major mechanism by which
      appropriate amounts of glucose are produced to supply energy to the central
      nervous system, without causing long-term increases of the plasma glucose
      concentration. It is hypothesised that the primary route by which insulin
      maintains control over glucose production is indirect and is mediated by
      regulation of non-esterified fatty acid release from the adipocyte. The question
      arises as to why evolution has chosen insulin to be secreted into the portal
      vein, if control of the liver is partially or primarily indirect. It is suggested
      that alterations in hepatic insulin clearance which attend increases in central
      adiposity are an important part of the compensation for insulin resistance and
      limit the necessity for up-regulation of insulin secretion in insulin resistance
      secondary to central adiposity. METHODS: Review of research from author's group
      and other laboratories. RESULTS: Data over the previous decade indicate that
      suppression of glucose output by increased insulin is a relatively slow process,
      much slower than the rate of binding of insulin to hepatocytes. One explanation
      is that insulin acts on an extrahepatic tissue, which in turn alters a signal to
      the liver, reducing glucose output. Additional evidence for an extrahepatic
      primary effect of insulin emerges from experiments in which insulin was given
      portally or peripherally at half the portal dose. Endogenous glucose production
      was related to systemic, not portal insulin, supporting the concept that the
      primary step in insulin's action on liver is on some other tissue, altering
      signalling to the liver itself. Strong correlation between plasma non-esterified
      fatty acids (NEFA) and liver glucose output suggests that the primary effect is
      on the adipocyte. The primacy of the adipocyte locus for the insulin effect
      included data that insulin's action on liver is prevented when plasma NEFA are
      maintained, as well as data showing proportional decline in glucose production
      and fatty acids when antilipolysis is induced by an adenosine agonist. Why then,
      from an evolutionary point of view is insulin secreted into the portal vein?
      Institution of central adiposity in dogs with fat feeding causes hepatic insulin
      resistance, at least partially due to the provision of NEFA in portal blood. The
      initial response to resistance is enhanced beta-cell sensitivity to glucose; a
      secondary compensation is, however, a substantial reduction in liver clearance,
      allowing for a greater proportion of secreted insulin to reach muscle, where it
      can more efficiently stimulate glucose utilisation. CONCLUSION/INTERPRETATION:
      Non-esterified fatty acids act as a signal as well as a metabolic substrate. They
      can regulate glucose utilisation in muscle and apparently are important signals
      to the liver and the beta cells as well. The importance of portal vein NEFA
      concentrations to the function of the liver could explain insulin resistance of
      the liver with central pattern obesity.

PMID- 10952472
TI  - "Lipoblastoma-like" lipoatrophy induced by human insulin: morphological evidence
      for local dedifferentiation of adipocytes?

PMID- 10952473
TI  - Oral vasoactive medication in intermittent claudication: utile or futile?
AB  - OBJECTIVE: To evaluate the role of orally administered vasoactive medication in
      the management of intermittent claudication. SETTING: We limited our study to the
      products on the market in Belgium: cinnarizine, cyclandelate, isoxsuprine,
      naftidrofuryl, pentoxifylline, xanthinol nicotinate and buflomedil. DATA SOURCES:
      We conducted a systematic literature search involving Medline, International
      Pharmaceutical Abstracts, the Cochrane Library, direct contact with marketing
      companies and key authors, snowballing and Science Citation Index search. We
      looked for randomised placebo-controlled trials (RCTs) in patients with Fontaine
      stage II, in which pain-free and/or maximal walking distance were measured using
      a standardised exercise test. For isoxsuprine and xanthinol nicotinate, no trials
      conforming to these criteria were found. Thirty-six trials on cinnarizine,
      cyclandelate, buflomedil, naftidrofuryl and pentoxifylline met our inclusion
      criteria. STUDY SELECTION: After quality assessment, 26 trials were excluded,
      mainly because of short trial duration (less than 12 weeks), small sample size
      (less than 30 patients) and/or failure to report details on variability (standard
      deviation or confidence limits). For cinnarizine and cyclandelate, none of the
      three selected RCTs was included. DATA EXTRACTION: For buflomedil, of six
      published RCTs, two were included after quality assessment, each showing a
      marginally positive effect of buflomedil versus placebo. For naftidrofuryl, nine
      RCTs were selected; six were included of which five showed a significant positive
      result. The likelihood of publication bias and the heterogeneity of the results
      within and between trials precluded a meta-analysis. For pentoxifylline, of the
      18 selected RCTs, only two could be included, both with inconclusive results.
      CONCLUSION: A national consensus conference, based on this review, concluded that
      health resources should be allocated to prevention and rehabilitation of
      intermittent claudication rather than to reimbursement of these products with
      doubtful efficacy.

PMID- 10952474
TI  - A randomized controlled assessment of the systemic activity of budesonide when
      given once or twice daily via Turbuhaler.
AB  - OBJECTIVE: To compare the effects on the hypothalamo-pituitary-adrenal (HPA) axis
      of budesonide, delivered via Turbuhaler at doses of 800 microg once daily in the
      morning or evening or 400 microg twice daily. METHODS: Healthy men (n = 24)
      received four treatments in random order: budesonide, 800 Fg in the morning and
      placebo in the evening; budesonide, 800 microg in the evening and placebo in the
      morning; budesonide, 400 microg in the morning and evening; placebo in the
      morning and evening. Each treatment was given for 1 week, with a 2-week washout
      period between treatments. Blood samples for measurement of plasma cortisol were
      obtained before the evening dose on day 6 of each treatment period and over the
      following 22 h. RESULTS: All three budesonide regimens produced a statistically
      significant reduction (mean 16-19%) in the area under the curve of plasma
      cortisol concentration versus time over 22 h (AUC0-22h) compared with placebo.
      There were no statistically significant differences among the three regimens.
      These reductions in plasma cortisol concentrations were not considered to be
      clinically significant. Analysis of the fractional AUCs measured 0-10 h and 10-22
      h after dosing showed that evening dosing had a greater effect on nocturnal
      cortisol than morning dosing; daytime cortisol was reduced by all treatments.
      CONCLUSION: There was no significant difference between the effects on plasma
      cortisol of budesonide 400 microg twice daily and 800 microg once daily in the
      morning or evening.

PMID- 10952475
TI  - Psychomotor effects of zaleplon and thioridazine coadministration.
AB  - OBJECTIVE: To assess the potential pharmacokinetic and pharmacodynamic
      interaction of zaleplon and thioridazine administered concomitantly in healthy
      volunteers. METHODS: A three-period, double-blind, randomized crossover study of
      the psychomotor effects of single oral doses of zaleplon 20 mg alone,
      thioridazine 50 mg alone, or the two drugs administered concomitantly was
      performed in 12 healthy subjects. Pharmacodynamic testing was performed before,
      and at 1, 2, 4, and 8 h after drug administration. Critical flicker fusion (CFF),
      tapping rate (TR), reaction time (RT) with dominant and nondominant hands, and
      digit symbol substitution test (DSST) were used to assess psychomotor
      performance. RESULTS: Pharmacokinetic results showed that coadministration of
      zaleplon and thioridazine did not alter the pharmacokinetic profile of either
      drug. In both CFF and TR tests, values for change from baseline with combined
      treatment were not significantly different from those with thioridazine at any
      time point, indicating no pharmacodynamic interaction. RT test values with
      coadministered treatment were significantly different from those with
      thioridazine alone at 1 h after administration, indicating additivity. Supra
      additivity was observed in DSST results at 1, 2, and 4 h. There was no
      interaction at 8 h. CONCLUSION: The results of single-dose administration showed
      an additive pharmacodynamic interaction between zaleplon and thioridazine at 1 h
      in one of four tests and supra-additivity for 4 h in another test. This
      interaction is relatively short in duration due to the short half-life of
      zaleplon.

PMID- 10952476
TI  - Clinical efficacy, safety and pharmacokinetics of a newly developed controlled
      release morphine sulphate suppository in patients with cancer pain.
AB  - OBJECTIVE: To compare the efficacy, safety and pharmacokinetics of a newly
      developed controlled-release suppository (MSR) with MS Contin tablets (MSC) in
      cancer patients with pain. METHODS: In a double-blind, randomised, two-way cross
      over trial, 25 patients with cancer pain were selected with a morphine (M) demand
      of 30 mg every 12 h. Patients were divided into two groups. Group 1 received
      active MSC (30 mg) and placebo MSR, followed by placebo MSC and active MSR (30
      mg) each for a period of 5 days. Group 2 started with active MSR and placebo MSC,
      followed by active MSC and placebo MSR, each for a period of 5 days. Blood for
      determination of plasma concentration of morphine (M) and its 3- and 6
      glucuronides (M3G, M6G) was collected, and area under the plasma concentration
      time curve (AUC)0-12 h, peak plasma concentration (Cmax), time to reach Cmax
      (tmax), and CO and C12 of M, M6G and M3G were determined on day 5 and day 10.
      Intensity of pain experienced by each patient was assessed every 2 h on a 0-10
      scale, while side effects and rescue medication were recorded. RESULTS: Twenty
      patients (ten patients in each group) completed the study. A pronounced inter
      patient variability in plasma concentrations of M, M3G and M6G was observed after
      administration of both forms. Apart from the C0 and C12, no significant
      differences in AUC0-12 h, tmax and Cmax of morphine between the rectal and oral
      route of administration were found. In the case of the metabolites, it was found
      that AUC0-12 h and Cmax of M6G, and AUC0-12 h, Cmax, C0 and C12 of M3G after
      rectal administration were significantly lower than after oral administration.
      However, apart from the tmax of M6G, none of the pharmacokinetic parameters of M,
      M6G or M3G met the criteria for bioequivalence. There were no significant (P =
      0.44) differences in pain intensity score between the oral and rectal forms
      within the two groups, regardless of the treatment sequence. No treatment
      differences in nausea, sedation or the demand on escape medication (acetaminophen
      tablets) between the rectal and oral forms were observed. CONCLUSION: The newly
      developed controlled-release M suppository is safe and effective and may be a
      useful alternative for oral morphine administration in patients with cancer pain.

PMID- 10952478
TI  - Genotype and phenotype of cytochrome P450 2D6 in human immunodeficiency virus
      positive patients and patients with acquired immunodeficiency syndrome.
AB  - OBJECTIVE: To examine the distribution of the cytochrome P450 (CYP) CYP2D6
      phenotype and its relation to genotype, concomitant medication, and disease state
      in human immunodeficiency virus (HIV)-positive patients. DESIGN: A cross
      sectional study with a longitudinal component compared individual genotypes for
      CYP2D6 to the CYP2D6 phenotype. METHODS: Sixty-one predominately male Caucasian,
      HIV-positive patients were recruited and CYP2D6 genotypes [extensive metabolizer
      (EM) or poor metabolizer (PM)] determined by polymerase chain reaction (PCR)
      based amplification, followed by restriction fragment-length analysis. The
      patients were also phenotyped using dextromethorphan (DM) to determine their
      respective enzyme activity and assigned either a CYP2D6 EM or PM phenotype.
      Complete medical and treatment histories were compiled. A total of 44 patients
      were tested longitudinally. RESULTS: Fifty-nine patients (97%) possessed an EM
      genotype, consistent with previously observed distributions in demographically
      similar populations. In healthy seronegative populations, genotype and phenotype
      have been shown to be essentially interchangeable measures of CYP2D6 activity. In
      this cohort, 2 of the 59 patients with an EM genotype expressed a PM phenotype.
      In addition, 4 EM patients were less extensive DM metabolizers than any of the
      patients receiving medication known to inhibit CYP2D6. This apparent shift toward
      the PM phenotype from the EM genotype was associated with the presence of active
      illness. CONCLUSION: Changes may occur in HIV-positive patients such that their
      CYP2D6 activity approaches that of PMs, despite having an EM genotype. Neither
      active disease nor drug interactions alone explain the shift.

PMID- 10952477
TI  - Effect of fluconazole on plasma fluvastatin and pravastatin concentrations.
AB  - OBJECTIVE: To study the effects of fluconazole on the pharmacokinetics of
      fluvastatin and pravastatin, two inhibitors of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase. METHODS: Two separate randomised, double-blind,
      two-phase, crossover studies with identical study design were carried out. In
      each study, 12 healthy volunteers were given a 4-day pretreatment with oral
      fluconazole (400 mg on day 1 and 200 mg on days 2-4) or placebo, according to a
      randomisation schedule. On day 4, a single oral dose of 40 mg fluvastatin (study
      I) or 40 mg pravastatin (study II) was administered orally. Plasma concentrations
      of fluvastatin, pravastatin and fluconazole were measured over 24 h. RESULTS: In
      study 1, fluconazole increased the mean area under the plasma fluvastatin
      concentration-time curve (AUC0-infinity) by 84% (P < 0.01), the mean elimination
      half-life (t1/2) of fluvastatin by 80% (P < 0.01) and its mean peak plasma
      concentration (Cmax) by 44% (P < 0.05). In study II, fluconazole had no
      significant effect on the pharmacokinetics of pravastatin. CONCLUSIONS:
      Fluconazole has a significant interaction with fluvastatin. The mechanism of the
      increased plasma concentrations and prolonged elimination of fluvastatin is
      probably inhibition of the CYP2C9-mediated metabolism of fluvastatin by
      fluconazole. Care should be taken if fluconazole or other potent inhibitors of
      CYP2C9 are prescribed to patients using fluvastatin. However, pravastatin is not
      susceptible to interactions with fluconazole or other potent CYP2C9 inhibitors.

PMID- 10952479
TI  - Intravesical administration of 5-aminolevulinic acid (5-ALA). Safety and
      pharmacokinetics of 5-ALA and its metabolite protoporphyrin IX.
AB  - OBJECTIVE: In an open study, the local and systemic side effects and
      pharmacokinetics of 5-aminolevulinic acid (5-ALA) and the fluorescent metabolite
      protoporphyrin IX (PPIX) were investigated after intravesical administration for
      the fluorescent photodetection of superficial bladder carcinoma. PATIENTS AND
      METHODS: In 20 patients with confirmed bladder carcinoma, 5-ALA was introduced
      into the bladder 2 h (15 patients) and 4 h (5 patients) before an elective
      endoscopic resection. The 5-ALA and PPIX levels in the plasma were determined
      before and up to 10 h after application, and in the urine 2 h or 4 h after
      application. RESULTS: The plasma level of 5-ALA rose rapidly, the maximal
      concentration (340 ng/ml) being reached in 0.55 h (2 h) or 0.62 h (4 h). The
      elimination half-life of 5-ALA amounted to 0.74 h (2 h) or 0.79 h (4 h). In five
      of the patients, there was a measurable plasma concentration which ranged from
      the detection limit of 4.3 ng/ml to 14 ng/ml between 2 h and 5 h after
      application, and then fell below the detection limit after 9 h. Absorption of 5
      ALA by the bladder was low, i.e. less than 1% of the total amount applied. During
      a period of observation of 96 h, no 5-ALA-specific side effects appeared.
      CONCLUSION: Because of the small quantity of 5-ALA resorbed following its
      intravesical administration, only minimal concentrations of PPIX that are
      responsible for producing side effects can be metabolised in the plasma.
      Therefore, no systemic side effects are to be expected after the intravesical
      administration of 5-ALA.

PMID- 10952480
TI  - Pharmacokinetics and organ distribution of intravenous and oral methylene blue.
AB  - OBJECTIVE: To determine the pharmacokinetics and organ distribution of i.v. and
      oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy
      in oncology. METHODS: The concentration of methylene blue in whole blood was
      measured using high-performance liquid chromatography in seven volunteers after
      i.v. and oral administration of 100 mg methylene blue with and without mesna. The
      distribution of methylene blue in different tissues was measured in rats after
      intraduodenal and i.v. application. RESULTS: The time course of methylene blue in
      whole blood after i.v. administration showed a multiphasic time course with an
      estimated terminal half-life of 5.25 h. Following oral administration, the area
      under the concentration-time curve was much lower (9 nmol/min/ml vs 137
      nmol/min/ml). Co-administration of mesna, which could influence distribution by
      ion-pairing, did not alter the pharmacokinetics. The urinary excretion of
      methylene blue and its leucoform was only moderately higher after i.v.
      administration (18% vs 28% dose). Intraduodenal administration to rats resulted
      in higher concentrations in intestinal wall and liver but lower concentrations in
      whole blood and brain than i.v. methylene blue. CONCLUSIONS: Differences in organ
      distribution of methylene blue are mainly responsible for the different
      pharmacokinetics after oral and i.v. administration. If methylene blue acts in
      the liver, where ifosfamide is primarily activated to reactive and potentially
      toxic metabolites, oral and i.v. methylene blue are likely to be equally
      effective. However, if the site of action is the central nervous system, i.v.
      methylene blue which results in much higher concentrations in brain seems
      preferable.

PMID- 10952481
TI  - High thiamine diphosphate concentrations in erythrocytes can be achieved in
      dialysis patients by oral administration of benfontiamine.
AB  - OBJECTIVE: The influence of either orally administered S-benzoylthiamine-O
      monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was
      tested in a randomised, two-group comparison study in 20 end-stage renal disease
      (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine
      diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its
      activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes.
      METHODS: After ingestion of a single dose of either 100 mg thiamine nitrate
      (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to
      214 micromol thiamine), the blood levels of thiamine phosphate esters were
      analysed by means of high-performance liquid chromatography for a 24-h period.
      The TDP concentration in erythrocytes was calculated using the haematocrit and
      TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were
      measured before and 10 h after administration. The pharmacokinetics of TDP in
      blood were compared with healthy subjects of other studies retrieved from
      database query. RESULTS: Regarding the blood concentrations of TDP, the patients
      with ESRD had a 4.3 times higher area under the concentration time curve after
      benfotiamine administration than after thiamine nitrate. After benfotiamine
      administration, the peak plasma concentration of TDP exceeded that in healthy
      subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in
      erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml
      after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0
      ng/ml after thiamine nitrate administration. The ratio between the maximum
      erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the
      benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P <
      0.001). After 24 h, it was 2.11+/-0.4 and 1.23+/-0.2, respectively. The
      transketolase activity increased from 3.54+/-0.7 microkat/l initially to 3.84+/
      0.6 microkat/l after benfotiamine intake (P = 0.02) and from 3.71+/-0.8
      microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08).
      Likewise, alpha-ETK decreased from initially 1.10+/-0.07 to 1.04+/-0.04 (P =
      0.04) and from 1.12+/-0.05 to 1.08+/-0.06 (P = 0.09). After 24 h, the
      phosphorylation ratio in whole blood decreased from 12.9+/-6.9 initially to 5.6+/
      3.2 after benfotiamine administration (P = 0.02) and from 13.5+/-7.3 to 9.0+/-4.8
      (P = 0.03) after administration of thiamine nitrate. No correlation between
      erythrocyte TDP concentration and transketolase activity and/or alpha-ETK was
      observed in ESRD patients, either before or 10 h after administration.
      CONCLUSION: Compared with thiamine nitrate, the oral administration of
      benfotiamine leads to higher TDP concentrations in erythrocytes accompanied with
      a significant improvement of the erythrocyte transketolase activity in ESRD
      patients.

PMID- 10952483
TI  - Hydroquinine pharmacokinetics after oral administration in adult patients with
      muscle cramps.
AB  - OBJECTIVE: This study was conducted to determine the pharmacokinetic properties
      of hydroquinine after oral administration in adult patients with muscle cramps.
      The main reason for this study was the poor availability of pharmacokinetic data,
      hindering the design of studies to explore the possible relationship between
      hydroquinine concentrations and effects. METHODS: Sixteen adult patients with a
      clinical history of muscle cramps were given once-daily oral doses of 300 mg
      hydroquinine hydrobromide for 4 days. Serum and saliva samples were taken
      following a predefined schedule until 24 h after the last dose. Urine was
      collected during the study period. Hydroquinine concentrations were measured, and
      calculations were made of pharmacokinetic parameters using non-linear curve
      fitting. RESULTS: Pharmacokinetics of hydroquinine could be best described using
      a one-compartment open model. After oral administration, hydroquinine was rapidly
      absorbed (mean +/- SD: maximum concentration 2.43+/-0.68 mg/ 1; time to maximum
      concentration 1.4+/-1.2 h; lag time 0.54+/-0.50 h). With an elimination half-life
      of 10.9+/-6.1 h, steady-state was reached in several days. The distribution
      volume was 1.24+/-0.29 l/kg, total clearance was 6.7+/-3.2 l/h. The measured
      unbound hydroquinine fraction was 8.6+/-3.0%. No correlation was found between
      saliva and serum concentrations. Cumulative urinary excretion of unchanged
      hydroquinine 24 h after the first dose was 35.5+/-9.2 mg. CONCLUSION:
      Pharmacokinetic properties of hydroquinine are roughly similar to those of
      quinine. The unchanged fraction of hydroquinine excreted in urine is higher than
      that reported for quinine. Saliva hydroquinine concentrations could not be
      related to serum values. Steady-state trough or other fixed-time serum
      concentrations may prove useful for further optimisation of hydroquinine dosage.

PMID- 10952482
TI  - Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and
      ritonavir: comparison with ketoconazole.
AB  - OBJECTIVE: Biotransformation of triazolam to its alpha-hydroxy and 4-hydroxy
      metabolites by human liver microsomes in vitro was used as an index of human
      cytochrome P450 3A (CYP3A) activity. RESULTS: The reaction was strongly inhibited
      by co-incubation with the viral protease inhibitors ritonavir (IC50 = 0.14
      microM) and amprenavir (IC50 = 2.5 2.9 microM), and by the azole derivative
      ketoconazole (IC50 = 0.07 microM). Pre-incubation of microsomes with ritonavir or
      amprenavir increased inhibitory potency (IC50 reduced to 0.07 microM and 1.4
      microM, respectively). This was not the case with ketoconazole. CONCLUSIONS:
      Thus, ritonavir and amprenavir are highly potent mechanism-based inhibitors of
      human CYP3A isoforms.

PMID- 10952484
TI  - Deviations from evidence-based prescribing of non-steroidal anti-inflammatory
      drugs in three European regions.
AB  - OBJECTIVE: We examined to what extent the evidence of the relative
      gastrointestinal toxicity with non-steroidal anti-inflammatory drugs (NSAIDs) was
      implemented in clinical practice in Bologna, Italy, Funen, Denmark, and
      Stockholm, Sweden, areas with accurate computerised information on prescriptions
      purchased by defined populations. METHODS: We ranked each NSAID by purchased
      volume in defined daily doses during September 1996 and compared it with the
      ranking of gastrointestinal complications from a meta-analysis of controlled
      epidemiological studies published between 1986 and 1994. We restricted our
      comparison to those NSAIDs that accounted for 90% of the use and within this
      DU90% segment we determined the proportion of "high risk" (azapropazone,
      ketoprofen, piroxicam) and "low risk" (ibuprofen, diclofenac) drugs with respect
      to gastrointestinal toxicity. RESULTS: In Funen, Denmark, we found the best NSAID
      profile (63% low risk/11% high risk) while Bologna, Italy, had the other extreme
      (26% low risk/38% high risk), with Stockholm, Sweden, in between (43% low
      risk/20% high risk). CONCLUSION: Our study suggests that factors other than
      evidence-based medicine had a dominating impact on the use of prescription NSAIDs
      in 1996.

PMID- 10952485
TI  - Drug-drug interactions of new active substances: mibefradil example.

PMID- 10952486
TI  - Nuclear medicine in the developing countries: is there a role?

PMID- 10952487
TI  - Therapeutic advantages of Auger electron- over beta-emitting radiometals or
      radioiodine when conjugated to internalizing antibodies.
AB  - Recent studies suggest a higher anti-tumour efficacy of internalizing monoclonal
      antibodies (MAbs) when labelled with Auger electron emitters, as compared with
      beta-emitters. The aim of this study was to compare the anti-tumour efficacy and
      toxicity of the internalizing MAb, CO17-1A, labelled with Auger electron emitters
      (125I, (111)In) versus conventional beta(-)-emitters (131I, 90Y) in a colon
      cancer model, and to assess whether the residualizing radiometals may have
      therapeutic advantages over the conventionally iodinated conjugates.
      Biodistribution studies of 125I-, (111)In- or 88Y-labelled CO17-1A were performed
      in nude mice bearing subcutaneous human colon cancer xenografts. For therapy, the
      mice were injected with either unlabelled or 125I-, 131I-, (111)In- or 90Y
      labelled CO17-1A IgG2a, whereas control groups were left untreated or were given
      a radiolabelled isotype-matched irrelevant antibody. The influence of
      internalization was assessed by comparing the results with those obtained with an
      anti-carcinoembryonic antigen (CEA) antibody which does not internalize to a
      relevant extent. The maximum tolerated activities (MTA) and doses (MTD) of each
      agent were determined. Myelotoxicity and potential second-organ toxicities, as
      well as tumour growth, were monitored. Bone marrow transplantation (BMT) was
      performed in order to enable dose intensification. Radiometals showed
      significantly better tumour-to-blood ratios than the respective iodinated
      conjugates. The MTAs of 131I- and 125I-CO17-1A without artificial support were
      11.1 MBq (300 microCi) and 111 MBq (3 mCi), respectively; the MTA of the metals
      was reached at 4 MBq (100 microCi) for 90Y-, and at 85 MBq (2.3 mCi) for (111)In
      CO17-1A. Myelotoxicity was dose limiting in all cases. BMT enabled an increase in
      the MTA to 15 MBq (400 microCi) of 131I-labelled CO17-1A, to 4.4 MBq (120
      microCi) of 90Y-labelled CO17-1A, and to 118 MBq (3.2 mCi) of (111)In-labelled
      CO17-1A, while the MTA of 125I-CO17-1A had not been reached at 185 MBq (5 mCi)
      with BMT. Whereas no significant therapeutic effects were seen with unlabelled
      CO17-1A, tumour growth was retarded significantly with its radiolabelled forms.
      The therapeutic results were significantly (P<0.01) better with both Auger
      electron emitters (125I and (111)In) than with the beta-emitters, and, in
      accordance with the biodistribution data, a trend towards better therapeutic
      results was found with radiometals (more complete remissions) as compared with
      radioiodine. In contrast, at equitoxic doses, no significant difference was
      observed in the therapeutic efficacy of 131I- versus 125I-labelled non
      internalizing anti-CEA antibody, F023C5. These data suggest that, at equitoxic
      doses, the therapeutic efficacy of internalizing MAbs labelled with Auger
      electron emitters, such as 125I or (111)In, is superior to that of internalizing
      MAbs labelled with conventional beta-emitters. The lower toxicity of Auger
      electron emitters may be due to the short path length of their low-energy
      electrons, which can reach the nuclear DNA only if the antibody is internalized
      (as is the case in antigen-expressing tumour tissue, but not in the stem cells of
      the red marrow).

PMID- 10952488
TI  - Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8)
      radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's
      lymphoma.
AB  - Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to
      estimate the radiation absorbed dose to normal organs and bone marrow from 90Y
      Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase
      I/II, multicenter trial. The trial was designed to determine the dose of
      Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled
      antibody given prior to the radioconjugate to clear peripheral blood B cells and
      optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin
      [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received (111)In
      Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a
      therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion
      of the chimeric, unlabeled antibody Rituximab. Following administration of
      (111)In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major
      organ radioactivity versus time estimates were calculated using regions of
      interest. Residence times were computed and entered into the MIRDOSE3 computer
      software program to calculate estimated radiation absorbed dose to each organ.
      Initial analyses of estimated radiation absorbed dose were completed at the
      clinical site. An additional, centralized dosimetry analysis was performed
      subsequently to provide a consistent analysis of data collected from the seven
      clinical sites. In all patients with dosimetry data (n=56), normal organ and red
      marrow radiation absorbed doses were estimated to be well under the protocol
      defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation
      absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72
      4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor
      radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted
      between hematologic toxicity and the following variables: red marrow radiation
      absorbed dose, blood T(1/2), blood AUC, plasma T(1/2), and plasma AUC. It is
      concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated
      doses results in acceptable radiation absorbed doses to normal organs. The only
      toxicity of note is hematologic and is not correlated to red marrow radiation
      absorbed dose estimates or T(1/2), reflecting that hematologic toxicity is
      dependent on bone marrow reserve in this heavily pretreated population.

PMID- 10952489
TI  - Non-invasive grading of oligodendrogliomas: correlation between in vivo metabolic
      pattern and histopathology.
AB  - Several studies have shown that the prognosis of oligodendrogliomas is dependent
      on their histological grade. In order to identify a non-invasive method for the
      primary diagnosis and follow-up of these tumours, we investigated the
      relationship between their in vivo metabolism, assessed by positron emission
      tomography (PET), and their histological grade assessed at the same time. Forty
      seven patients with histologically confirmed oligodendrogliomas were
      investigated. Conventional neuroradiological assessment by computed tomography
      and magnetic resonance imaging (MRI) was performed in all the patients. All the
      histology slices were reviewed by the same pathologist after referral from
      various pathology laboratories. The PET investigation included a carbon-1
      methionine (11C-MET) uptake study and, in the majority of cases, a fluorine-18
      fluorodeoxyglucose (18F-FDG) uptake study, in order to investigate at the same
      time both amino acid metabolism and glycolysis. The sampled tumour region of
      interest (ROI) was defined from the T1-weighted 3D MR scan matched with the PET
      scan. Tracer concentration in each voxel of the tumour ROI was divided by the
      mean concentration in an ROI of the same size located in the healthy brain
      tissue. For each tumour and each tracer, we characterized the metabolic pattern
      on the basis of the mean and the maximum tumour to healthy tissue concentration
      ratio, and also the standard deviation and range of the ratios, which indicate
      the degree of metabolic heterogeneity of the tumour. The histological criteria
      for differentiating between high- and low-grade tumours were those of the WHO
      and, partially, of the Sainte-Anne-Daumas-Duport classification. Highly
      significant differences between high- and low-grade oligodendrogliomas (Mann
      Whitney test: P<0.0001) were observed for all the assessed parameters of 11C-MET
      uptake. On the other hand, the pattern of 18F-FDG uptake showed only moderate
      differences between the two tumour groups.

PMID- 10952490
TI  - Dipyridamole and exercise SPET provide different estimates of myocardial
      ischaemic areas: role of the severity of coronary stenoses and of the increase in
      heart rate during exercise.
AB  - In patients unable to perform a maximal exercise test, dipyridamole single-photon
      emission tomography (SPET) has a higher capacity than exercise SPET to detect
      coronary artery disease (CAD). However, in patients with myocardial ischaemia who
      are able to perform a maximal exercise test, it is not known whether these two
      tests may be equally used to assess the areas of myocardial ischaemia. This study
      was aimed at comparing the results provided by dipyridamole and exercise SPET in
      CAD patients with documented exercise myocardial ischaemia. Forty CAD patients
      who had undergone exercise thallium-201 SPET and who had myocardial ischaemia
      documented by an unequivocally positive exercise test underwent an additional
      201Tl SPET study after dipyridamole infusion and low-level (40 W) exercise. The
      extent of defects was compared between the two tests and predictors of discrepant
      results were sought among data from exercise testing and coronary angiography.
      The extent of SPET defects was equivalent between the two tests in only 11
      patients (28%), larger defects being observed with exercise in 18 [average
      difference: 12%+/-5% of left ventricle (LV)] and with dipyridamole in 11 (average
      difference: 15%+/-11% of LV). The best independent predictors of discrepancies
      between the two tests were: (1) increase in heart rate at exercise SPET, with
      defects being smaller at exercise than after dipyridamole in none of the patients
      with an increase >60 bpm (0/14), but in 42% of the others (11/26; P=0.004); and
      (2) an ischaemic territory related to a <70% coronary stenosis, for which SPET
      defects were always induced at exercise (10/10) but in only 30% (3/10) with
      dipyridamole (P=0.0004). Exercise and dipyridamole SPET provide different
      estimates of myocardial ischaemic areas. Dipyridamole allows the unmasking of
      perfusion abnormalities in patients who have low increases in heart rate at
      exercise SPET. However, dipyridamole is also much less efficient at inducing
      perfusion abnormalities in the ischaemic areas supplied by coronary stenoses of
      intermediate severity at rest angiography.

PMID- 10952491
TI  - Relative preservation of peripheral lung function in smoking-related pulmonary
      emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET.
AB  - In this study the cross-sectional functional differences between the central and
      peripheral lung in smokers with pulmonary emphysema were evaluated by lung
      perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The
      subjects were 81 patients with a long-term smoking history and relatively
      advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and
      six healthy non-smokers. Regional lung functional difference between the
      peripheral and central lung was assessed in the upper, middle and lower lung
      zones by technetium-99m macroaggregated albumin SPET and dynamic 133Xe SPET. The
      distribution of emphysematous changes was assessed by density-mask computed
      tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of
      less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones
      of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of
      lung function in the peripheral lung, with a curvilinear band of normal perfusion
      (a stripe sign) and a significantly faster 133Xe half-clearance time (T(1/2))
      than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central
      dominant LAA distributions on density-mask CT images, but the remaining 32 zones
      did not show any regional preference in LAA distribution. Conversely, 117 (24.0%)
      lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and
      LAA distributions, with significantly prolonged T(1/2) in the peripheral lung
      area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary
      emphysema and all the lung zones of the healthy subjects and patients with non
      obstructive lung diseases did not show a stripe sign, and no differences were
      observed in T(1/2) values and LAA distributions between the central and
      peripheral lung. Relative preservation of peripheral lung function seems to be a
      characteristic feature in smoking-related pulmonary emphysema, and may indicate a
      lower susceptibility of peripheral parenchyma to the development of this disease.

PMID- 10952492
TI  - Infarct size and recurrence of ventricular arrhythmias after defibrillator
      implantation.
AB  - Infarct size as determined by perfusion imaging is an independent predictor of
      mortality after implantable cardioverter defibrillator (ICD) implantation in
      patients with coronary artery disease (CAD) and life-threatening ventricular
      arrhythmias (VA). However, its value as a predictor of VA recurrence and
      hospitalisation after ICD implantation is unknown. Therefore, the objective of
      this study was to evaluate whether infarct size as determined by perfusion
      imaging can help to identify patients who are at high risk for recurrence of VA
      and hospitalisation after ICD implantation. We studied 56 patients with CAD and
      life-threatening VA. Before ICD implantation, all patients underwent a uniform
      study protocol including a thallium-201 stress-redistribution perfusion study. A
      defect score as a measurement of infarct size was calculated using a 17-segment 5
      point scoring system. Study endpoints during follow-up were documented episodes
      of appropriate anti-tachycardia pacing and/or shocks for VA and cardiac
      hospitalisation for electrical storm (defined as three or more appropriate ICD
      interventions within 24 h), heart failure or angina. After a mean follow-up of
      470+/-308 days, 22 patients (39%) had recurrences of VA. In univariate analysis,
      predictors for recurrence were: (a) ventricular tachycardia (VT) as the initial
      presenting arrhythmia (86% vs 59% for patients without ICD therapy, P=0.04), (b)
      treatment with beta-blockers (36% vs 68%, P=0.03) and (c) a defect score (DS) >
      or = 20 (64% vs 32%, P=0.03). In multivariate analysis, VT as the presenting
      arrhythmia (chi2=5.51, P=0.02) and a DS > or = 20 (chi2=4.22, P=0.04) remained
      independent predictors. Cardiac hospitalisation was more frequent in patients
      with a DS > or = 20 (44% vs 13% for patients with DS < 20, P=0.015) and this was
      particularly due to more frequent hospitalisations for electrical storm (24% vs
      3% for patients with DS < 20, P=0.037). The extent of scarring determined by
      perfusion imaging can separate patients with CAD into high- and low-risk groups
      for recurrence of VA and cardiac hospitalisation after ICD implantation.

PMID- 10952493
TI  - Cardiac adrenergic denervation in patients with non-Q-wave versus Q-wave
      myocardial infarction.
AB  - In spite of smaller infarct size and better preserved left ventricular function
      the long-term prognosis after a non-Q-wave infarction is not better than after a
      Q-wave infarction. In fact, the risk of sudden cardiac death is higher in
      patients with a non-Q-wave infarction than in patients with a Q-wave infarction.
      One possible reason for postinfarction arrhythmias is cardiac adrenergic
      denervation resulting from myocardial infarction. In this study we compared
      cardiac adrenergic innervation after non-Q-wave and Q-wave infarctions. Single
      photon emission tomography using iodine-123 metaiodobentzylguanidine (MIBG) and
      technetium-99m sestamibi (MIBI) tracers were conducted in order to compare
      cardiac adrenergic denervation and myocardial perfusion in 12 patients with a non
      Q-wave infarction and 15 patients with a Q-wave infarction. MIBG and MIBI defects
      were determined as regional uptake < or = 30% of maximal myocardial activity. The
      size of MIBI defects calculated as a percentage of left ventricular mass was
      significantly smaller in patients with a non-Q-wave infarction than in patients
      with a Q-wave infarction (4%+/-3% vs 9%+/-7%, P<0.05, respectively). According to
      the maximal serum creatine kinase activity, less myocardium was damaged in
      patients with a non-Q-wave infarction than in patients with a Q-wave infarction
      (502+/-436 IU/l vs 1878+/-1265 IU/l, P<0.001). In spite of this, the extent of
      MIBG defects was similar in patients with a non-Q-wave and patients with a Q-wave
      infarction (21%+/-18% vs 23%+/-12%, respectively). In addition, the size of MIBG
      defect correlated with the infarct size (maximal creatine kinase activity)
      (r=0.52, P<0.05) after a Q-wave infarction but not after a non-Q-wave infarction.
      In conclusion, despite a smaller infarct size in non-Q-wave infarct patients, the
      extent of cardiac adrenergic denervation was similar in patients with a non-Q
      wave and patients with a Q-wave infarction. In addition, the extent of cardiac
      adrenergic denervation was related to the infarct size in patients with a Q-wave
      infarction but not in patients with a non-Q-wave infarction.

PMID- 10952494
TI  - Infection imaging using whole-body FDG-PET.
AB  - The purpose of this study was to evaluate fluorine-18 fluorodeoxyglucose positron
      emission tomography (FDG-PET) for the detection of soft tissue and bone
      infections. Forty-five PET examinations in 39 patients (26 male, 13 female, age
      range 27-86 years) with suspected infectious foci were examined with whole- or
      partial-body PET scans using FDG. Twenty-seven scans were done in patients with
      soft tissue and 18 in patients with bone infections. Corrected and uncorrected
      transaxial PET images were acquired. Seven hundred and twelve body regions in
      these 45 PET scans were evaluated. Pathological findings were graded using a
      confidence scale from A to E (A, definitive infection; E, no infection). Disease
      status was defined in all patients by culture, biopsy or surgery and clinical
      follow-up. In 45 PET scans there were 40 true-positive, four false-positive and
      one false-negative findings. Twelve foci suspected to be infectious in nature on
      the basis of other imaging examinations were identified as negative by PET, thus
      representing true-negative findings. Sensitivities for the patients with soft
      tissue (STI) and bone infections (BI) and for the pooled data were 96%, 100% and
      98%, respectively. As the calculation of specificity is not straightforward, it
      was calculated on a per lesion as well as on a per body region basis to permit
      estimation of an upper and a lower limit. On a per lesion basis, specificities
      were 70% (STI), 83% (BI) and 75% for the pooled data and on a per body region
      basis (dividing the body into 22 regions) they were 99% (STI), 99% (BI) and 99%
      for the pooled data. One false-negative result was found in a patient with
      cholangitis. It is concluded that PET appears to be a highly sensitive method to
      detect infectious foci. Specificity is more difficult to estimate, but is
      probably in the range from 70% to above 90%.

PMID- 10952495
TI  - Multivariate analysis of prognostic factors for differentiated thyroid carcinoma
      in children.
AB  - At most centres, the standard treatment for differentiated thyroid cancer (DTC)
      comprises total thyroidectomy, radioiodine treatment and thyroid-stimulating
      hormone (TSH) suppressive therapy. There is, however, considerable disagreement
      over the appropriate treatment for DTC in children. Some dispute the use of total
      thyroidectomy and/or question the routine application of iodine-131 therapy in
      children. The aim of this study was to perform a retrospective analysis of
      treatment results and prognostic factors for DTC in children treated at our
      centre. The study included 109 children with DTC (aged 6-17 years). The primary
      treatment comprised total thyroidectomy in 81 cases, radioiodine therapy in 85
      cases and TSH suppressive therapy with L-thyroxine in all patients. Uni- and
      multivariate analysis of prognostic factors for disease-free survival was
      performed using the Cox regression method. The actuarial survival rate was 100%,
      and the 5- and 10-year actuarial disease-free survival rates were 80% and 61%
      respectively. Univariate analysis revealed that older age, total thyroidectomy
      and radioiodine treatment had a positive impact on disease-free survival whereas
      there were no statistical differences with regard to the child's sex,
      histological type of cancer or lymph node status. On multivariate analysis,
      radical surgery was estimated to be the most significant factor (P=0.007) for
      disease-free survival, while less than total thyroidectomy increased the relative
      risk of relapse by a factor of 10. Radioiodine treatment decreased the relative
      risk of relapse by a factor of 5, but with borderline significance (P=0.07).
      Permanent postoperative complications were observed in 17% of children: in 11
      laryngeal palsy occurred, in six there was hypoparathyroidism, and one suffered
      from both. It is concluded that total thyroidectomy and radioiodine treatment
      significantly improve recurrence-free survival in children and should be
      routinely applied even in young children as the primary treatment of DTC.

PMID- 10952496
TI  - Treatment of Bowen's disease with a specially designed radioactive skin patch.
AB  - Bowen's disease can be treated by various methods, including surgical excision,
      cryosurgery, laser ablation, curettage, Mohs' microsurgery and ionizing
      radiation. Radiotherapy has been a useful therapeutic modality in the treatment
      of Bowen's disease and other skin cancers in areas which are difficult to excise,
      especially the central areas of the face, including eyelids, nose and lips. To
      overcome some of the disadvantages of external radiotherapy, a specially designed
      skin patch coated with high-energy beta-emitter holmium-166 was made for topical
      application at our institute. Twenty-nine sites of Bowen's disease in eight
      patients, confirmed by skin biopsy, were treated with 166Ho patches. The patches
      were applied to the surface of skin cancers for 30-60 min for a total radiation
      dose of 35 Gy (3500 rads). One to two weeks after application of the 166Ho patch,
      desquamation, erythema or erosion developed in treated sites, but these acute
      radiation reactions healed gradually with epithelial regeneration, and they
      showed good functional and cosmetic results without any complications. Follow-up
      biopsies were performed 1-5 months after 166Ho patch therapy, and they did not
      show any signs of Bowen's disease. One to two years after treatment with 166Ho
      skin patches, there were no recurrences of Bowen's diseases and no late
      complications. The 166Ho patch is an effective and convenient alternative method
      for the treatment of Bowen's disease that yields good cosmetic and functional
      results.

PMID- 10952497
TI  - Improved efficiency for MRI-SPET registration based on mutual information.
AB  - Mutual information has been proposed as a criterion for image registration. The
      criterion is calculated from a two-dimensional grey-scale histogram of the image
      pair being registered. In this paper we study how sparse sampling can be used to
      increase speed performance using the registration algorithm of Maes et al. (IEEE
      Trans Med Imaging 1997; 16: 187-198) with a focus on registration of MRI-SPET
      brain images. In particular we investigate how sparse sampling and parameters
      such as the number of bins used for the grey-scale histograms and smoothing of
      the data prior to registration affect accuracy and robustness of the
      registration. The method was validated using both simulated and human data. Our
      results show that sparse sampling introduced local maxima into the mutual
      information similarity function when the number of bins used for the histograms
      was large. To speed up registration while retaining robustness, smoothing of the
      data prior to registration was used and a coarse to fine subsampling protocol,
      where the number of bins in the histograms were dependent on the subsampling
      factor, was employed, For the simulated data, the method was able to recover
      known transformations with an accuracy of about 1 mm. Using the human data, there
      were no significant differences in the recovered transformation parameters when
      the suggested subsampling scheme was used compared with when no subsampling was
      used, but there was a more than tenfold increase in speed. Our results show that,
      with the appropriate choice of parameters, the method can accurately register MRI
      SPET brain images even when very efficient sampling protocols are used.

PMID- 10952498
TI  - A simple method for preparing radioactive capsules in colon transit study.
AB  - Colon transit study is currently performed by delivering technetium-99m or indium
      111 labelled activated charcoal to the colon in a methacrylate-coated capsule
      (coated capsule). However, the coating procedure is complicated and methacrylate
      has not been approved by the Food and Drug Administration. Therefore, a simpler
      method is needed for the clinical routine use of colon transit study. In this
      study, we used a commercial empty enteric capsule and a coated capsule for the
      measurement of colon transit time. We compared the in vitro stability and in vivo
      scintigraphy of 99mTc-labelled activated charcoal in the coated capsule and the
      enteric capsule to evaluate the possibility of clinical usage of the enteric
      capsule for colon transit time study. Activated charcoal powder was mixed with
      49mTc-diethylene triamine pentaacetic acid (DTPA) and vaporized to dryness. The
      dry 99mTc-DTPA activated charcoal was loaded into the coated capsule and the
      enteric capsule. In vitro stability study was performed by immersing these
      capsules in a colourless buffer of variable pH which mimicked the conditions in
      the stomach and the small bowel. Capsule disruption was determined. Colon transit
      scintigraphy with 99mTc-DTPA charcoal was performed in five normal volunteers
      using these two capsules. The in vitro stability of these two types of capsule
      was similar and the colon transit scintigraphy findings were almost identical.
      Most capsules dissolved in the ascending colon and very few in the terminal
      ileum. It is concluded that enteric capsule is a suitable alternative to coated
      capsule for measurement of colon transit.

PMID- 10952499
TI  - Use of PET to monitor the response of lung cancer to radiation treatment.
AB  - Approximately 170,000 people are diagnosed with lung cancer in the United States
      each year. Many of these patients receive external beam radiation for treatment.
      Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is
      increasingly being used in evaluating non-small cell lung cancer and may be of
      clinical utility in assessing response to treatment. In this report, we present
      FDG PET images and data from two patients who were followed with a total of eight
      and seven serial FDG PET scans, respectively, through the entire course of their
      radiation therapy. Changes in several potential response parameters are shown
      versus time, including lesion volume (V(FDG)) by PET, SUVav, SUVmax, and total
      lesion glycolysis (TLG) during the course of radiotherapy. The response
      parameters for patient 1 demonstrated a progressive decrease; however, the
      response parameters for patient 2 showed an initial decrease followed by an
      increase. The data presented here may suggest that the outcome of radiation
      therapy can be predicted by PET imaging, but this observation requires a study of
      additional patients.

PMID- 10952500
TI  - Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET
      in healthy volunteers.
AB  - Dopamine transporter imaging is a valuable tool to investigate the integrity of
      the dopaminergic neurons. To date, several reports have shown an age-associated
      decline in dopamine transporters in healthy volunteers. Although animal studies
      suggest an effect of gender on dopamine transporter density, this gender effect
      has not yet been confirmed in human studies. To study the influence of age and
      gender on dopamine transporter imaging in healthy volunteers, we performed single
      photon emission tomography imaging with [123I]FP-CIT to quantify dopamine
      transporters. Forty-five healthy volunteers (23 males and 22 females) were
      included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h
      after injection of +/-110 MBq [123I]FP-CIT. An operator-independent volume of
      interest analysis was used for quantification of [123I]FP-CIT binding in the
      striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was
      found to decrease significantly with age. Moreover, we found a high variance in
      [123I]FP-CIT binding in young adults. Finally, females were found to have
      significantly higher [123I]FP-CIT binding ratios than males. This effect of
      gender on [123I]FP-CIT binding ratios was not related to age. The results of this
      study are consistent with findings from previous studies, which showed that
      dopamine transporter density declines with age. The intriguing finding of a
      higher dopamine transporter density in females than in males is in line with
      findings from animal studies.

PMID- 10952501
TI  - Uses and limitations of renal scintigraphy in renal transplantation monitoring.
AB  - The value of thrice weekly technetium-99m mercaptoacetyltriglycine renography
      after renal transplantation was investigated in 213 consecutive transplants. A
      grading system was used: 0 = normal renogram; 1 = normal uptake, reduced
      excretion; 2 = normal uptake, flat excretion curve; 3 = rising curve; 4 = reduced
      rate of uptake, rising curve and reduced absolute uptake; 5 = minimal uptake. The
      initial renogram grade (RG) was primarily a marker of ischaemic damage, being
      poorer with cadaver donation, long cold ischaemia (>24 h), and high donor and
      recipient age. High primary RG predicted primary graft non-function, long time to
      graft function, low discharge Cr EDTA clearance and low 1- and 5-year graft
      survival. Discharge RG predicted late (>6 months) graft loss. RG was highly
      correlated (P<0.001) with creatinine and creatinine clearance, and changes in RG
      were correlated with changes in renal function. A change in RG of 0.5 was non
      specific, while a change of 1 or more predicted clinical complications in 95% of
      cases. The negative predictive value was low (58%). RG change antedated clinical
      diagnosis in only 38% of cases, and in only 14% of acute rejections did an RG
      change of 1 or more antedate a rising creatinine. RG did not contribute to the
      differential diagnosis between acute rejection, acute tubulointerstitial
      nephropathy and cyclosporine toxicity. In conclusion, an initial renography after
      transplantation is valuable as it measures ischaemic damage and predicts duration
      of graft non-function and both short and long-term graft survival. A review of
      the literature suggests that the indication for serial scintigraphic monitoring
      for functioning grafts is less certain: the diagnostic specificity is
      insufficient for it to be the definitive investigation for common diagnostic
      problems and it does not give sufficient advance warning of impending problems.

PMID- 10952503
TI  - The ongoing evolution of analytical chemistry

PMID- 10952502
TI  - Improved interpretation of cerebral PET with respect to structural MRI changes
      using combined voxel-based statistical mapping.

PMID- 10952504
TI  - Challenges for the analytical chemistry curriculum

PMID- 10952505
TI  - Finding mismatches the bacterial way.

PMID- 10952506
TI  - Test tubes without walls.

PMID- 10952507
TI  - How pure is this junk?

PMID- 10952509
TI  - Driven by shear force

PMID- 10952508
TI  - Microscale muscles.

PMID- 10952511
TI  - Miniature ion trap arrays

PMID- 10952510
TI  - Autonomous underwater MS

PMID- 10952513
TI  - Division awards

PMID- 10952512
TI  - Determining chirality with MS.

PMID- 10952514
TI  - Advancing the science of column selectivity.

PMID- 10952516
TI  - Graphite furnace AAS

PMID- 10952515
TI  - Advancing hyphenated chromatographic systems

PMID- 10952517
TI  - Undergraduate research: a capstone learning experience

PMID- 10952518
TI  - Orientation-insensitive methodology for second harmonic generation. 1. Theory
AB  - The use of second harmonic generation as a means to probe either adsorption
      isotherms or the kinetics of adsorption/desorption is limited by the fact that
      the detected signal is dependent upon both surface coverage and molecular
      orientation. Thus, the second harmonic intensity must be tediously corrected if
      either the mean orientation angle or the width of the orientation distribution
      changes as a function of surface coverage. In this study, a new mathematical view
      of the second harmonic intensity as a function of excitation polarization is
      developed. This new approach predicts an experimental geometry that is relatively
      insensitive to molecular orientation, such that appropriate choice of the
      excitation polarization rotation angle allows for direct measurement of surface
      coverage. The theory is presented for the three common dominant
      hyperpolarizability tensor elements, beta(z'z'z'), beta(x'x'x'), and
      beta(x'x'z').

PMID- 10952519
TI  - Orientation-insensitive methodology for second harmonic generation. 2.
      Application to adsorption isotherm and kinetics measurements
AB  - In this work, the theory presented in part 1 for an experimental configuration
      that provides a means to isolate surface coverage measurements by SHG from
      coverage-dependent molecular orientation changes was tested. The adsorption
      isotherm for disperse red 1 on glass was found to be quite sensitive to the
      choice of excitation polarization rotation angle due to a coverage-dependent
      change in molecular orientation. Appropriate selection of the polarization
      rotation angle, as dictated by the theory presented in part 1, yielded reliable
      adsorption isotherm results that were essentially independent of changes in
      molecular orientation. Use of a standard experimental approach (e.g., probing the
      intensity of p-polarized second harmonic for p-polarized fundamental), resulted
      in large error (nearly 100%) in the calculated equilibrium constant. The
      adsorption isotherm for rhodamine 6G on glass was found to be relatively
      insensitive to the choice of polarization rotation angle since its apparent
      orientation angle did not change significantly as a function of coverage.

PMID- 10952520
TI  - Airborne cell analysis.
AB  - A miniaturized analysis system for the study of living cells and biochemical
      reactions in microdroplets was developed. The technique utilizes an in-house
      developed piezoelectric flow-through droplet dispenser for precise reagent supply
      and an ultrasonic levitator for contactless sample handling. A few-cell study was
      performed with living primary adipocytes. Droplets (500 nL) containing 3-15
      individual cells were acoustically levitated. The addition of beta-adrenergic
      agonists into the levitated droplet using the droplet dispenser stimulated
      adipocyte lipolysis, leading to free fatty acid release and a consequent pH
      decrease of the surrounding buffer. The addition of insulin antagonized lipolysis
      and hence also the decrease in pH. The changes in pH, i.e., the cell response in
      the droplet, were followed using a pH-dependent fluorophore continuously
      monitored by fluorescence imaging detection. An image analysis computer program
      was employed to calculate the droplet intensities. To counteract droplet
      evaporation, found to affect the fluorescence intensities, a separate dispenser
      was used to continually add water, thus keeping the droplet volume constant.

PMID- 10952521
TI  - Surface characterization of aspirin crystal planes by dynamic chemical force
      microscopy.
AB  - Tapping mode (TM) atomic force microscopy (AFM) has been applied in a novel
      fashion to characterize and distinguish the (001) and (100) surfaces of
      individual aspirin crystals. The surface characterization was achieved by
      amplitude-phase, distance (a-p,d) measurements employing gold-coated AFM probes
      functionalized with self-assembled monolayers (SAM). Experiments using model
      probes coated with -CH3 and -COOH terminated SAMs have been performed on the two
      aspirin crystal planes (001) and (100). Results indicate that the hydrophobic 
      CH3 terminated AFM probes had a greater degree of interaction with the crystal
      plane (001), whereas the -COOH terminated AFM probes had a larger interaction
      with the crystal plane (100). Interpretation of these data, based upon the
      chemistries of the probes, correlates with current understanding of the crystal
      surface chemistry derived from X-ray diffraction data and dissolution rate
      studies.

PMID- 10952522
TI  - Laser-induced fluorescence detection by liquid core waveguiding applied to DNA
      sequencing by capillary electrophoresis.
AB  - A new laser-induced fluorescence detector for capillary electrophoresis (CE) is
      described. The detector is based on transverse illumination and collection of the
      emitted fluorescent light via total internal reflection along the separation
      capillary. The capillary is coated with a low refractive index fluoropolymer and
      serves as a liquid core waveguide (LCW). The emitted light is detected end-on
      with a CCD camera at the capillary exit. The observed detection limit for
      fluorescein is 2.7 pM (550 ymol) in the continuous-flow mode and 62 fM in the CE
      mode. The detector is applied to DNA sequencing. One-color G sequencing is
      performed with single-base resolution and signal-to-noise ratio approximately 250
      for peaks around 500 bases. The signal-to-noise ratio is approximately 50 for
      peaks around 950 bases. Full four-color DNA sequencing is also demonstrated. The
      high sensitivity of the detector is suggested to partly be due to the efficient
      rejection of scattered laser light in the LCW. The concept should be highly
      suitable for capillary array detection.

PMID- 10952523
TI  - Patterning and characterization of surfaces with organic and biological molecules
      by the scanning electrochemical microscope.
AB  - A novel approach for micropatterning of surfaces with organic and biological
      microstructures using the scanning electrochemical microscope (SECM) is
      described. The approach is based on the introduction of the spatial resolution by
      local deposition of gold particles followed by monolayer formation and
      functionalization. Specifically, gold patterns were deposited locally on silicon
      wafers with the SECM as a result of the controlled anodic dissolution of a gold
      microelectrode. The gold patterns were further used as microsubstrates for
      assembling cystamine monolayers to which either fluoresceine isothiocyanate (FIT)
      or glucose oxidase (GOD) were covalently attached. Characterization of the
      organic monolayers, as well as the biological activity of the enzyme patterns,
      was carried out by fluorescence microscopy and the SECM, respectively.

PMID- 10952524
TI  - Prestructured MALDI-MS sample supports.
AB  - Prestructured MALDI-MS sample supports have been developed that simplify high
      throughput analysis of biomolecules and improve the detection sensitivity. The
      mass spectrometric sample support is coated with a thin layer of hydrophobic
      Teflon that carries an array of 200-microm gold spots, which provide hydrophilic
      sample anchors. Each transferred sample droplet contacts one anchor, on top of
      which, after solvent evaporation, the sample is exclusively deposited due to the
      strongly water repellent nature of the Teflon surface. The initial matrix
      concentration is kept low, enabling sample up-concentration by more than 2 orders
      of magnitudes before crystallization commences. As a result, the detection
      sensitivity is improved as documented by mass spectra recorded from 100 amol of
      various peptides, 1 fmol of a DNA 20 mer, and 5 fmol of a 130 bp PCR product.
      Size and spacing of the hydrophilic anchors are optimized for MALDI-MS
      performance (sample spot size approximately = laser irradiation spot size), for
      short analysis times (predetermined sample coordinates), and for high throughput
      sample preparation (sample anchor array according to the 1536 microtiter plate
      format).

PMID- 10952525
TI  - Thermometric sensing of peroxide in organic media. Application to monitor the
      stability of RBP-retinol-HRP complex.
AB  - The stability of horseradish peroxidase (HRP) in aqueous and organic solvents is
      applied to develop a simple thermometric procedure to detect the binding of
      retinoic acid-HRP conjugate to retinol binding protein (RBP). Butanone peroxide
      (BP) in organic phase and hydrogen peroxide in aqueous phase is detected
      thermometrically on a HRP column, immobilized by cross-linking with
      glutaraldehyde on controlled pore glass (CPG). Acetone, acetonitrile, methanol,
      and 2-butanol are used for detection of BP, in the flow injection analysis (FIA)
      mode. A linear range between 1 and 50 mM BP is obtained in all the organic
      solvents with a precision of 5-7% (CV%). The magnitude and nature of the
      thermometric response is significantly different in each organic solvent. The
      stability of HRP in the organic phase is used to study the stability of a
      retinoic acid-HRP conjugate bound to immobilized RBP. The response of HRP (to 20
      mM BP) in the retinoic acid-HRP conjugate is used as an indicator of the
      stability of the RBP-retinoic acid-HRP complex, after challenges with various
      organic/aqueous solvents. Both immobilized HRP and RBP are stable at least for 6
      months. The effect of o-phenylene diamine on the thermometric response of HRP is
      also investigated. A scheme for the design of a thermometric retinol (vitamin A)
      biosensor is proposed.

PMID- 10952526
TI  - Preparation and characterization of thermoresponsive poly(N-isopropylacrylamide
      co-acrylic acid) hydrogels: studies with electroactive probes
AB  - A new method of preparing thermoresponsive hydrogels consisting of N
      isopropylacrylamide (NIPA) and acrylic acid (AA), with a well-defined
      concentration of an electroactive probe, 1,1'-ferrocenedimethanol (Fc(MeOH)2), is
      described, and a comparison of the physical and electrochemical properties of
      NIPA-AA gels with those of aqueous solutions is presented. The NIPA-AA gels
      undergo a discontinuous volume phase transition at 45 degrees C; this transition
      results in a release of approximately 40% of the solution mass from the gel
      phase. Characterization of hydrogels with electroactive probes is performed using
      electroanalytical techniques and FTIR and UV/vis spectroscopies. Steady-state
      voltammetry and chronoamperometry at platinum disk microelectrodes are used to
      measure the diffusion coefficient of Fc(MeOH)2 in gels under a wide range of
      experimental conditions. Similar diffusion coefficients for Fc(MeOH)2 in NIPA-AA
      gels are obtained by either electroanalytical technique at temperatures lower
      than 20 degrees C. The uncertainty in the Fc(MeOH)2 concentration in the gels,
      resulting from the discontinuous volume change transition, necessitated the use
      of concentration-independent chronoamperometric data (i.e. the chronoamperometric
      response divided by the steady-state current obtained at sufficiently long times)
      to obtain reliable diffusion coefficient values for Fc(MeOH)2. For temperatures
      above the volume phase transition, changes of concentration of Fc(MeOH)2 are
      detected in a copolymeric collapsed phase.

PMID- 10952528
TI  - Spectroelectrochemical sensing based on multimode selectivity simultaneously
      achievable in a single device. 6. Sensing with a mediator
AB  - The use of a mediator to detect a nonabsorbing analyte during
      spectroelectrochemical modulation is demonstrated. The charge-selective composite
      film of Nafion-SiO2 was used to entrap the mediator, Ru(bipy)3(2+). The change in
      deltaA as detected by attenuated total reflection was then observed upon addition
      of the analyte, ascorbate. The effects of scan rate, concentration of mediator,
      film thickness, and analyte charge were studied to achieve optimal sensor
      conditions. The model sensor exhibited a linear range from 0.26 to 2.0 mM (R2 =
      0.998).

PMID- 10952527
TI  - Amperometric quantification of polar organic solvents based on a tyrosinase
      biosensor.
AB  - A novel amperometric biosensor for quantification of the electrochemically inert
      polar organic solvents based on tyrosinase electrode was preliminarily reported.
      The biosensor was fabricated by simply syringing an aqueous solution of
      tyrosinase/PVAVP (PVAVP: copolymer of poly(vinyl alcohol) grafting with 4
      vinylpyridine) onto glassy carbon electrode surface followed by drying the
      modified electrode at +4 degrees C in a refrigerator. The current generated from
      electrochemical reduction of quinone is a probe signal. The biosensor can be used
      for quantification of polar organic solvents, and its mechanism was characterized
      with in situ steady-state amperometry-quartz crystal microbalance experiments.
      The detection limit, sensitivity, and dynamic range for certain organic solvents
      are dependent on the kind and concentration of the substrate probe and the
      hydrophobicity of the immobilization matrix. The response time for all the tested
      organic solvents is less than 2 min.

PMID- 10952529
TI  - Lifetime-based pH sensor system based on a polymer-supported ruthenium(II)
      complex
AB  - A new luminescence lifetime-based pH sensor system is described. The system is
      based on [Ru(Ph2phen)2DCbpy]2+ (DCbpy = 4,4'-dicarboxy-2,2'-bipyridine)
      immobilized in a mixed domain network copolymer utilizing hydrophobic regions in
      a hydrophilic, water-swellable, poly(ethylene oxide) matrix. The metal complex
      binds irreversibly to the hydrophobic domains leaving the pH-sensing COOHs
      projecting into an aqueous-rich poly(ethylene oxide) region. The complex shows a
      strong pH dependence of its lifetime (3-4-fold) and provides a usable pH range of
      about 3-5. The long (approximately 1 micros) excited-state lifetime and visible
      absorption of the sensor simplifies measurements. A model for the combined pH and
      oxygen-quenching sensitivity of the complex is provided; this allows use of the
      pH system over a wide range of oxygen concentrations. The combined polymer sensor
      is easy to prepare and requires no covalent chemistry. Further, the polymers
      enhance the luminescence of the complex and minimize interference from oxygen
      quenching.

PMID- 10952530
TI  - Determination of selenium(IV) by a photooxidized 3,3'
      diaminobenzidine/perfluorinated polymer mercury film electrode
AB  - A new, and easily fabricated, chemically modified electrode for the determination
      of selenium(IV) was examined by cathodic square-wave stripping voltammetry. This
      new electrode consisted of an anion-exchange perfluorinated polymer (Tosflex)
      coated thin mercury film electrode containing photooxidized 3,3'-diaminobenzidine
      (ODAB). The coating solution of Tosflex and ODAB was spin-coated on a glassy
      carbon electrode followed by electroplating of a thin film of mercury. During the
      preconcentration, ODAB was reduced electrochemically and selenium was accumulated
      simultaneously onto the electrode by interacting with the reduced ODAB. After a 5
      min preconcentration period, linear response was observed from 0.5 to 50 ppb
      selenium, and the detection limit was 0.1 ppb. The proposed method does not
      require a darkened room, which was required in many of the previous methods
      involving 3,3'-diaminobenzidine. In addition, the resistance to interference from
      surface-active compounds was improved by incorporating Tosflex in the film.

PMID- 10952531
TI  - Computer-aided design and experimental investigation of a hydrodynamic device:
      the microwire electrode
AB  - The development and application of a new electrochemical device using a computer
      aided design strategy is reported. This novel design is based on the flow of
      electrolyte solution past a microwire electrode situated centrally within a large
      duct. In the design stage, finite element simulations were employed to evaluate
      feasible working geometries and mass transport rates. The computer-optimized
      designs were then exploited to construct experimental devices. Steady-state
      voltammetric measurements were performed for a reversible one-electron-transfer
      reaction to establish the experimental relationship between electrolysis current
      and solution velocity. The experimental results are compared to those predicted
      numerically, and good agreement is found. The numerical studies are also used to
      establish an empirical relationship between the mass transport limited current
      and the volume flow rate, providing a simple and quantitative alternative for
      workers who would prefer to exploit this device without the need to develop the
      numerical aspects.

PMID- 10952532
TI  - Achievement of near-reversible behavior for the
AB  - Voltammetric studies in the absence of added supporting electrolyte are presently
      dominated by the use of near-steady-state microelectrode techniques and
      millimolar or lower depolarizer concentrations. However, with this methodology,
      large departures from conventional migration-diffusion theory have been reported
      for the [Fe(CN)6](3-/4-) process at both carbon fiber and platinum microdisk
      electrodes. In contrast, data obtained in the present study reveal that use of
      the transient cyclic voltammetric technique at glassy carbon, gold, or platinum
      macrodisk electrodes and K4[Fe(CN)6] or K3[Fe(CN)6] concentrations of 50 mM or
      greater provides an approximately reversible response in the absence of added
      electrolyte. It is suggested that the use of very high [Fe(CN)6](3-) and
      [Fe(CN)6](4-) concentrations overcomes problems associated with a diffuse double
      layer and that large electrode surface areas and faster potential sweep rates
      minimize electrode blockage and passivating phenomena that can plague
      voltammetric studies at microelectrodes. The cyclic voltammetry of the
      [Fe(CN)6](3-/4-) couple at a range of concentrations at macroelectrodes in the
      absence of added inert electrolyte is compared with that obtained in the presence
      of 1 M KCl. The enhanced influences of uncompensated resistance, migration, and
      natural convection arising from density gradients under transient conditions at
      macrodisk electrodes also are considered.

PMID- 10952533
TI  - Use of the ferrocene oxidation process to provide both reference electrode
      potential calibration and a simple measurement (via semiintegration) of the
      uncompensated resistance in cyclic voltammetric studies in high-resistance
      organic solvents
AB  - Because of its presumed ideal reversible behavior, the oxidation of ferrocene is
      widely used in cyclic voltammetric studies in highly resistive organic solvents
      as a means of reference electrode potential calibration. In this study, it is
      shown that a good estimate of the uncompensated resistance value, needed for
      reference potential correction and also frequently an input parameter in
      simulation of the theory, can be obtained simultaneously with the ferrocene
      reference potential measurement using a simple analysis based on the
      semiintegral. Application to cyclic voltammetric oxidation of ferrocene in
      dichloromethane (0.1 M NBu4PF6), under conditions where uncompensated resistances
      of approximately 2.5 komega are encountered, is used to illustrate the fidelity
      of the semiintegral method of analysis. Inclusion of this estimated resistance
      value as the input parameter in a commercially available digital simulation
      package confirms that the oxidation of ferrocene in dichloromethane represents a
      close-to-ideal diffusion-controlled reversible process. However, use of the
      semiintegral method of data analysis also enables detection of subtle forms of
      nonideality encountered with the ferrocene oxidation process in other media where
      kinetically controlled adsorption of the ferricenium cation may occur.

PMID- 10952534
TI  - Synthesis and application of submicrometer fluorescence sensing particles for
      lysosomal pH measurements in murine macrophages.
AB  - Phagocytosis of bioparticles such as bacteria and viruses by macrophages is a
      critical component of the immune response against infections. In this paper we
      describe the synthesis of submicrometer fluorescent particles with pH sensing
      capability. The particles are used to measure the pH and to monitor the effect of
      chloroquine, an antimalarial drug, on the pH in the lysosome, the cellular
      organelle involved in the phagocytosis process. The synthesis of the pH sensing
      particles is realized by the covalent attachment of amine reactive forms of
      Oregon Green (pH sensitive dye) and Texas Red (pH insensitive dye) to the surface
      of amino-modified submicrometer polystyrene particles. The particles are absorbed
      by J774 Murine Macrophages through phagocytosis and directed to lysosomes.
      Despite the high lysosomal levels of digestive enzymes and acidity, the absorbed
      particles remain stable for 12 h in the cells when they are stored in a PBS
      buffer solution at pH 7.4. The pH dynamic range of the sensing particles is
      between pH 4.5 and 7 with a sensitivity of 0.1 pH units. Exposure of the cells to
      chloroquine increases the lysosomal pH from 4.8 to 6.5. The effect is
      concentration-dependent.

PMID- 10952535
TI  - An ICP-OES method with 0.2% expanded uncertainties for the characterization of
      LiA1O2
AB  - An improved inductively coupled plasma-optical emission spectrometry (ICP-OES)
      method has been applied to the determination of Li and A1 mass fractions and the
      Li/A1 amount-of-substance ratio in representative samples of LiA1O2. This ICP-OES
      method has uncertainty on the order of 0.2%,(2,3) comparable to the best
      analytical methods. This method is based on several strategies, which are
      detailed in this work. The mean measured mass fractions of Li and A1 in eight
      samples were 0.10151 +/- 0.00016 (+/-0.16%) and 0.41068 +/- 0.00056 (+/-0.14%),
      and the mean Li/A1 amount-of-substance ratio was 0.9793 +/- 0.0017 (+/-0.17%).
      The uncertainty is dominated by sample handling and heterogeneity-about a factor
      of 2 larger than the ICP-OES instrumental uncertainties, which were 0.04% for A1
      and 0.07% for Li.

PMID- 10952536
TI  - Computer simulations of electrokinetic injection techniques in microfluidic
      devices
AB  - Computer simulations are used to study electrokinetic injections on microfluidic
      devices (microchips). The gated and pinched injection techniques are considered.
      Each injection technique uses a unique sequence of steps with different electric
      field distributions and field magnitudes in the channels to effectuate a virtual
      valve. The goal of these computer simulations is to identify operating parameters
      providing optimal valve performance. In the pinched injection, the conditions of
      both loading and dispensing steps were analyzed to reach a compromise between the
      sample plug spatial extent and its concentration. For the gated injection, the
      condition of leakage free valve operation was found for the sample loading step.
      The simulation results for the gated valve are compared with experimental data.

PMID- 10952538
TI  - Chemical vapor generation: atomic absorption by Ag, Au, Cu, and Zn following
      reduction of aquo ions with sodium tetrahydroborate(III)
AB  - Volatile species of Ag, Au, Cu, Zn, Cd, and As were generated at room temperature
      by the addition of sodium tetrahydroborate(III) to an acidified solution of the
      analytes. The vapor-phase species were rapidly transported to a heated quartz
      tube atomizer (QTA) for detection by atomic absorption spectrometry. A univariate
      approach was used to achieve optimized conditions and derive analytical figures
      of merit. The analytes are released from solution as molecular species (likely as
      metal hydrides) and are (partially) atomized in the QTA under nonoptimized
      conditions. Detection limits range from 1.8 (Zn) to 420 ng (Au). The efficiency
      of the generation process is estimated to be 92 +/- 4% for Au. Loss of analyte
      during transport to the QTA was minimized through use of the minimum length of
      narrow-bore Teflon transfer line possible.

PMID- 10952539
TI  - Monitoring of dye adsorption phenomena at a silica glass/water interface with
      total internal reflection coupled with a thermal lens effect
AB  - Thermal lens spectroscopy was combined with total internal reflectance
      spectroscopy to develop a novel, highly sensitive analytical method that can
      detect nonfluorescent as well as fluorescent analytes at surfaces and interfaces.
      It was verified that when the total internal reflection method is coupled with
      thermal lens spectroscopy (TIR-TLS), the thermal lens effect is induced by only
      the evanescent wave. The ability of depth profiling was shown. The detection
      limit of TIR-TLS was at an absorbance of 3.0 x 10(-5) unit for Sudan II acetone
      solution, which is better than that of attenuated total reflection by a factor of
      hundreds. In addition, the adsorption of acridine orange on silanol groups on a
      glass surface could be monitored directly by TIR-TLS, and the adsorption isotherm
      agreed well with Langmuir's model. The dependence of surface density of anionic
      silanol groups on pH was determined by TIR-TLS measurements of aqueous acridine
      orange solutions buffered in the pH range between 2.7 and 11.5.

PMID- 10952537
TI  - Fully automated chemiluminescence immunoassay of insulin using antibody-protein A
      bacterial magnetic particle complexes.
AB  - We report a fully automated sandwich immunoassay for the determination of human
      insulin using antibody-protein A-bacterial magnetic particle (BMP) complexes and
      an alkaline phosphatase-conjugated secondary antibody. BMPs bearing protein A
      MagA inserted on the external surface of the membrane were prepared in the
      Magnetospirillum sp. AMB-1 transconjugant for a protein A-magA fusion gene. MagA
      protein was used as an anchor to attach protein A onto the membrane. Protein A
      BMP complexes harvested from transconjugant AMB-1 were subsequently complexed
      with anti-human insulin antibodies by specific binding between the Z domain of
      protein A and the Fc component of IgG to form the antibody-protein A-BMP
      complexes. The complexes were quite monodisperse after the binding of the
      antibody. The BMPs' monodispersity resulted in high signal and low noise in the
      immunoassay. The luminescence intensity ((kilocounts/s)/microg of antibody) from
      antibody-protein A-BMP complexes after immunoreaction was higher than that from
      BMPs chemically conjugated to an antibody. This was explained by a difference in
      dispersion. The fully automated sandwich immunoassay system using antibody
      protein A-BMP complexes made possible precise assays of human insulin in serum.

PMID- 10952540
TI  - Analysis of nonderivatized neutral and sialylated oligosaccharides by
      electrospray mass spectrometry.
AB  - An HPLC/MS method has been developed that allows rapid, direct analysis of
      underivatized sialylated as well as neutral oligosaccharides. The method involves
      the separation of oligosaccharides from salts and proteins using RP-HPLC with a
      formic acid/acetonitrile/water mobile phase system and on-line electrospray mass
      spectrometry analysis in the positive ion mode. Under the solution conditions
      employed, both neutral and acidic (sialylated) oligosaccharides are protonated
      and therefore detected. In contrast to MALDI-TOF MS, no loss of sialic acid is
      observed when operating in the positive ion mode. Furthermore, the capability of
      this method to provide quantitative estimates of the relative abundance of each
      oligosaccharide mass has been demonstrated using fetuin as a model compound.

PMID- 10952542
TI  - Interpretation of mass spectra from organic compounds in aerosol time-of-flight
      mass spectrometry
AB  - Organic compounds containing a variety of functional groups have been analyzed
      using aerosol time-of-flight mass spectrometry. Both positive and negative laser
      desorption/ionization mass spectra have been acquired for compounds of relevance
      to ambient air particulate matter, including polycyclic aromatic hydrocarbons,
      heterocyclic analogues, aromatic oxygenated compounds such as phenols and acids,
      aliphatic dicarboxylic acids, and reduced nitrogen species such as amines. In
      many cases, positive ion mass spectra are similar to those found in libraries for
      70-eV electron impact mass spectrometry. However, formation of even-electron
      molecular ions due to adduct formation also plays a major role in ion formation.
      Negative ion mass spectra suggest that organic compounds largely disintegrate
      into carbon cluster fragments (C(n)- and C(n)H-). However, information about the
      heteroatoms present in organic molecules, especially nitrogen and oxygen, is
      carried dominantly by negative ion spectra, emphasizing the importance of
      simultaneous analysis of positive and negative ions in atmospheric samples.

PMID- 10952541
TI  - LC/MS/MS analyses of an oleander extract for cancer treatment.
AB  - An HPLC/MS/MS method has been developed for the characterization and
      quantification of the cardiac glycosides oleandrin, odoroside, neritaloside and
      the aglycone oleandrigenin, all contained in a patented-hot-water extract of
      Nerium oleander L (Anvirzel). Qualitative analysis of such extracts was achieved
      using a hybrid tandem quadrupole time-of-flight (QqTOF) mass spectrometer.
      Collision-induced dissociation (CID) mass spectra of oleandrin, oleandrigenin,
      odoroside, and neritaloside were obtained with greater than 5 ppm mass accuracy
      and resolution routinely in excess of 8000 (fwhm). The detection limit for
      oleandrin of 20 pg (injected) was realized when the precursor-to-product ion
      transition, m/z 577 --> 373, was monitored. We have also applied the analytical
      method to the determination of oleandrin, oleandrigenin, neritaloside, and
      odoroside in human plasma following an intramuscular injection of Anvirzel.

PMID- 10952543
TI  - Quantification of polycyclic aromatic hydrocarbons in the NIST standard reference
      material (SRM1649A) urban dust using thermal desorption GC/MS
AB  - A thermal desorption GC/MS technique has been developed for the quantification of
      polycyclic aromatic hydrocarbons (PAHs) in airborne particulate matter using the
      NIST Standard Reference Material (SRM1649a) Urban Dust. The technique was
      developed using standard linearity tests in order to establish optimum sample
      weights and optimum desorption and chromatographic parameters. This direct
      analysis technique eliminates the use of solvents in the sample preparation
      (reducing volatile component losses) and also significantly reduces the sample
      preparation time (no extraction procedure). The technique has been shown to give
      linearity in terms of the overall TIC response as well as for a prominent series
      of n-alkanes (C20-C33) and 10 NIST priority PAHs, 8 of which have been
      quantified. The technique is reported to be uniquely sensitive (PAH
      concentrations 2-6 mg kg(-1)) and reproducible (MW = 178-228 SD < or =0.228 mg
      kg(-1), < or =7%; MW = 252 SD < or =0.922 mg kg(-1), < or =33%) over the range of
      sample weights (1-5 mg). Such sample weights illustrate that the technique can be
      equally applied to the analysis of airborne particulate samples collected over
      short time periods (24-48 h) using only commonly used low-volume collection
      devices.

PMID- 10952544
TI  - Instrumentation and methodology for simultaneous excitation/detection of ions in
      an FTICR mass spectrometer
AB  - A method for direct and continuous detection of ion motion during different
      perturbation events of the fourier transform ion cyclotron resonance (FTICR)
      experiment is demonstrated. The modifications necessary to convert an ordinary
      FTICR cell into one capable of performing simultaneous excitation/detection (SED)
      using a capacitive network are outlined. With these modifications, a 200-fold
      reduction in the detection of the coupled excitation signal is achieved. This
      allows the unique ability not only to observe the response to the perturbation
      but to observe the perturbation event itself. SED is used successfully to monitor
      the ion cyclotron transient during single-frequency excitation, remeasurement and
      exciter-excite experiments.

PMID- 10952546
TI  - Liquid chromatographic separations with mobile-phase additives: influence of
      pressure on coupled equilibria
AB  - On the basis of equilibrium thermodynamics, pressure can cause a shift in
      equilibrium for any interaction that exhibits a change in partial molar volume.
      This shift in equilibrium can be observed in liquid chromatography as a pressure
      dependent shift in solute retention. In this paper, the impact of pressure on
      liquid chromatographic separations with mobile-phase additives is examined from
      both theoretical and experimental perspectives. The theoretical development for
      coupled-equilibria separations shown here is general and can be applied to any
      separation using mobile-phase additives. Predictions indicate that the coupled
      nature of these equilibria leads to pressure-induced perturbations in
      partitioning and complexation that can either compete with or complement one
      another. Using positional isomers and enantiomers as model solutes, experimental
      retention observations are fully consistent with these predictions, showing the
      diminution of individual pressure effects for competing cases and enhanced
      pressure effects for complementary cases. When pressure-induced changes in
      capacity or retention factor differ between individual solutes, changes in solute
      selectivity are predicted and observed. Using a C18 stationary phase with beta
      cyclodextrin as the mobile-phase additive, solutes studied here exhibit changes
      in selectivity ranging from - 7 to + 10% for a change in average pressure of
      approximately 215 bar. Perhaps the most dramatic change in selectivity is
      observed for the separation of positional isomers where pressure-induced changes
      in selectivity actually reverse solute elution order.

PMID- 10952545
TI  - Identification of uncommon plant metabolites based on calculation of elemental
      compositions using gas chromatography and quadrupole mass spectrometry.
AB  - Unknown compounds in polar fractions of Arabidopsis thaliana crude leaf extracts
      were identified on the basis of calculations of elemental compositions obtained
      from gas chromatography/low-resolution quadrupole mass spectrometric data. Plant
      metabolites were methoximated and silylated prior to analysis. All known peaks
      were used as internal references to construct polynomial recalibration curves of
      from raw mass spectrometric data. Mass accuracies of 0.005 +/- 0.003 amu and
      isotope ratio errors of 0.5 +/- 0.3% (A + 1/A), respectively, 0.3 +/- 0.2% (A +
      2/A), could be achieved. Both masses and isotope ratios were combined when the
      elemental compositions of unknown peaks were calculated. After calculation,
      compound identities were elucidated by searching metabolic databases,
      interpreting spectra, and, finally, by comparison with reference compounds. Sum
      formulas of more than 70 peaks were determined throughout single GC/MS
      chromatograms. Exact masses were confirmed by high-resolution mass spectrometric
      data. More than 15 uncommon plant metabolites were identified, some of which are
      novel in Arabidopsis, such as tartronate semialdehyde, citramalic acid,
      allothreonine, or glycolic amide.

PMID- 10952547
TI  - A method for determination of particle magnetic susceptibility with analytical
      magnetapheresis
AB  - We recently developed a new method for simple determination of particle magnetic
      susceptibility using analytical magnetapheresis. This new method does not require
      laborious calibration plots and trial susceptibility values as do previous
      analytical magnetapheresis methods. The new method is based on balancing channel
      flow rates and magnetically induced flow rates for particle deposition in
      analytical magnetapheresis. The maximal flow rate for complete particle
      deposition was determined experimentally and set to equal the magnetically
      induced flow rate for determining particle magnetic susceptibility. This magnetic
      susceptibility determination generally takes less than 20 min. Several
      magnetically susceptible and ion-labeled particles were tested using this new
      method. The carrier magnetic susceptibilities were varied, and erbium ion-labeled
      particles were studied experimentally, resulting in successful susceptibility
      determinations of erbium ion-labeled particles and yeasts. The precision of each
      measurement was generally approximately 10%. Experimental determination of
      particle magnetic susceptibilities differed by less than 10% from reference
      measurements taken using a superconducting quantum interference device
      magnetometer. This method can determine minimal susceptibilities on the order of
      10(-9) cgs. The minimum number of erbium labeling ions per particle required for
      complete deposition of silicas and yeasts was found to be 6.7 x 10(9). Analytical
      magnetapheresis shows good potential for use in simple determination of particle
      magnetic susceptibilities and should become a useful technique.

PMID- 10952548
TI  - Capillary electrophoresis separations on a planar chip with the column-coupling
      configuration of the separation channels
AB  - Some basic aspects of capillary electrophoresis (CE) separations on a poly(methyl
      methacrylate) chip provided with two separation channels in the column-coupling
      (CC) configuration and on-column conductivity detectors were studied. The CE
      methods employed in this study included isotachophoresis (ITP), capillary zone
      electrophoresis (CZE), and CZE with on-line ITP sample pretreatment (ITP-CZE).
      Hydrodynamic and electroosmotic flows of the solution in the separation
      compartment of the chip were suppressed, and electrophoresis was a dominant
      transport process in the separations performed by these methods. Very
      reproducible migration velocities of the separated constituents were typical
      under such transport conditions, and consequently, test analytes could be
      quantified by various ITP techniques with 1-2% RSD. The CC configuration of the
      separation channels provides means for an effective combination of an enhanced
      load capacity of the separation system with high detection sensitivities for the
      analytes in concentration-cascade ITP separations. In this way, for example,
      succinate, acetate, and benzoate could be separated also in instances when they
      were present in the loaded sample (1.2 microL) at 1 mmol/L concentrations while
      their limits of detection ranged from 8 to 12 micromol/L concentrations. A well
      defined ITP concentration of the analyte(s) combined with an in-column sample
      cleanup (via an electrophoretically driven removal of the matrix constituents
      from the separation compartment) can be integrated into the separations performed
      on the CC chip. These sample pretreatment capabilities were investigated in ITP
      CZE separations of model samples in which nitrite, phosphate, and fluoride (each
      at a 10 micromol/L concentration) accompanied matrix constituents (sulfate and
      chloride) at considerably higher concentrations. Here, both the concentration of
      the analytes and cleanup of the sample were included in the ITP separation in the
      first separation channel while the second separation channel served for the CZE
      separation of the ITP pretreated sample and the detection of the analytes.

PMID- 10952549
TI  - Fritless capillary columns for HPLC and CEC prepared by immobilizing the
      stationary phase in an organic polymer matrix
AB  - A new design of immobilized particle separation media for capillary liquid
      chromatography and electrochromatography has been developed. A mixture of
      porogenic solvents and methacrylate-based monomers is pumped through a packed
      column to provide, following a polymerization step, an organic matrix capable of
      holding the sorbent particles in place, thus rendering the end frits unnecessary.
      The new columns demonstrate excellent chromatographic performance in both CEC
      (reduced plate height [h]=1.1-1.5) and micro LC modes (h = 2.2-2.5), while
      minimizing secondary interactions encountered when silica-based entrapment
      matrixes are employed. In addition to delivering mechanically robust columns, the
      methacrylate matrix provides a mechanism for fine tuning of the electroosmotic
      flow velocity when 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) is
      incorporated into the polymerization mixture.

PMID- 10952550
TI  - NIST micronutrients measurement quality assurance program: characterizing
      individual participant measurement performance over time.
AB  - The mission of the Micronutrients Measurement Quality Assurance Program (M2QAP)
      at the National Institute of Standards and Technology is enhanced interlaboratory
      measurement comparability for fat-soluble vitamin-related measurands in human
      serum. We recently described improved tools for evaluating individual participant
      measurement performance in single interlaboratory comparison exercises; we here
      apply and extend these tools to the evaluation of participant performance over
      the entire 15-year history of the M2QAP. We describe and illustrate a set of
      interconnected graphical reporting tools for identifying long-term trends and
      single-exercise events. We document and discuss recurrent patterns we observe in
      the measurement performance characteristics for M2QAP participants. The graphical
      analysis techniques utilized may be applicable to other interlaboratory
      comparison programs.

PMID- 10952551
TI  - Modifier effects on column efficiency in packed-column supercritical fluid
      chromatography
AB  - We investigate the effects on column efficiency of methanol, acetonitrile,
      ethanol, and 1-propanol used as modifiers in packed-column SFC. C-18, phenyl, and
      cyano columns were used with both nonpolar and polar solutes. For highly retained
      nonpolar solutes, addition of modifier significantly increased apparent column
      efficiency, especially for the C-18 column. For polar solutes, the presence of
      modifier dramatically improved retention and efficiency with an apparent
      efficiency dependence on modifier type and amount. Temperature and pressure
      effects on efficiency were also studied.

PMID- 10952552
TI  - Approach for independent-matrix removal of polycyclic aromatic hydrocarbons from
      solid samples based on microwave-assisted Soxhlet extraction with on-line
      fluorescence monitoring
AB  - A flow injection interface for fluorometric monitoring of focused microwave
      assisted Soxhlet extraction (FMASE) is presented. This assembly allows real-time
      on-line monitoring of the PAHs extracted from solid samples in each Soxhlet cycle
      and provides qualitative and semi-quantitative information from natural and
      spiked samples. Hence, the extraction kinetics can be followed and the end of the
      leaching step determined independently of the sample matrix, thus avoiding
      excessive extraction times. The research also involves the study of the
      multivariate effects of the FMASE parameters by a central composite design. The
      method was applied to a certified reference material (CRM 524, BCR, industrial
      soil/organics) for quality assurance/validation. The total content of each
      analyte was determined by HPLC-fluorometric detection, and the results obtained
      demonstrated that FMASE is a technique as efficient as conventional Soxhlet to
      extract PAHs from soils but with a drastic reduction of both extraction time and
      organic solvent disposal.

PMID- 10952553
TI  - Label-free biochemical detection coupled on-line to liquid chromatography
AB  - The on-line coupling of a label-free optical biosensor to a HPLC system is
      described by combining the separation power of HPLC with the specificity of the
      biosensor system. A highly cross-reactive antibody against the pesticide
      isoproturon was used as model for affinity proteins. The binding strength of the
      antibody to the utilized pesticides was characterized with the biosensor, first.
      In the on-line coupling setup, the eluate of the HPLC was mixed continuously with
      the antibodies. The presence of antigens was detected by a reduction of the
      antibody binding to the transducer. This reduced binding was quantified by a
      differentiation of the sensor signal by applying a Savitzky-Golay algorithm.
      Limits of detection were found to be in the femtomole range without
      preconcentration, which is comparable to a study using fluorescence-based
      biochemical detection.

PMID- 10952554
TI  - Ligand-exchange chromatography at zirconium(IV) immobilized on IDA-type chelating
      polymer gel
AB  - Ligand-exchange chromatography of organo-acidic compounds at Zr(IV) immobilized
      on IDA-type chelating polymer gel using an aqueous mobile phase was studied, to
      obtain some insight into their retention on zirconia. Zirconium(IV) has no
      contribution to the retention of phenols, while appreciably enhancing that of
      benzoic acids and strongly or occasionally irreversibly adsorbing the potentially
      chelating substances. The presence of two stationary-phase species adsorbing
      benzoates was confirmed, and the retention over a wide pH range of 3.5-9.5 was
      quantitatively formulated. The correlation of the retention factor with the
      Bronsted acidity of samples and its dependence on pH were theoretically
      explained, and the performance of this chromatographic system was compared with
      that of zirconia.

PMID- 10952555
TI  - Determination of distribution coefficients of priority polycyclic aromatic
      hydrocarbons using solid-phase microextraction
AB  - The determination of distribution coefficients is important for prediction of the
      chemical pathways of organic compounds in the environment. Solid-phase
      microextraction (SPME) is a convenient and effective method to measure the
      distribution of chemicals in a two-phase system. In the present study, the SPME
      distribution coefficient (K(spme)) of 16 priority aromatic hydrocarbons (PAHs)
      was determined with 100-microm poly(dimethylsiloxane) (PDMS) and 85-microm
      polyacrylate (PA) fibers. The partition coefficients and LeBas molar volumes were
      used to describe the linearity of the log K(spme) values of PAHs. Also, the
      validation of the distribution coefficient was examined using different sample
      volumes. The extraction time was dependent on the types of PAHs, and 20 min to 60
      h was needed to reach equilibrium. The determined log K(spme) values ranged from
      3.02 to 5.69 and from 3.37 to 5.62 for 100-microm PDMS and 85-microm PA fibers,
      respectively. Higher K(spme) values of low-ring PAHs were observed using 85
      microm PA fiber. Good linear relationships between log K(ow) and log K(spme) for
      PAHs from naphthalene to benzo[alpha]pyrene and from naphthalene to chrysene for
      100-microm PDMS and 85-microm PA fibers, respectively, were obtained. The
      correlation coefficients were 0.969 and 0.967, respectively. The linear
      relationship between log K(spme) and the LeBas molar volume was only up to
      benz[alpha]anthracene for 85-microm PA fiber and up to chrysene for 100-microm
      PDMS fiber. Moreover, the effect of sample volume can be predicted using the
      partition coefficient theory and excellent agreement was obtained between the
      experimental and theoretical absorbed amounts of low-ring PAHs. This result shows
      that the determined log K(spme) is more accurate than the previous method for
      estimating analytes with log K(ow) < 6 as well as for predicting the partitioning
      behaviors between SPME fiber and water.

PMID- 10952556
TI  - Atmospheric pressure photoionization: an ionization method for liquid
      chromatography-mass spectrometry
AB  - Atmospheric pressure photoionization (APPI) has been successfully demonstrated to
      provide high sensitivity to LC-MS analysis. A vacuum-ultraviolet lamp designed
      for photoionization detection in gas chromatography is used as a source of 10-eV
      photons. The mixture of samples and solvent eluting from an HPLC is fully
      evaporated prior to introduction into the photoionization region. In the new
      method, large quantities of an ionizable dopant are added to the vapor generated
      from the LC eluant, allowing for a great abundance of dopant photoions to be
      produced. Because the ion source is at atmospheric pressure, and the collision
      rate is high, the dopant photoions react to completion with solvent and analyte
      molecules present in the ion source. Using APPI, at an LC flow rate of 200
      microL/min, it is possible to obtain analyte signal intensities 8 times as high
      as those obtainable with a commercially available corona discharge-atmospheric
      pressure chemical ionization source.

PMID- 10952557
TI  - Determination of distribution constants between a liquid polymeric coating and
      water by a solid-phase microextraction technique with a flow-through standard
      water system
AB  - This paper describes an optimized experimental system for determining
      water/polymer coating distribution constants and discusses the mechanism of
      extraction of high molecular weight compounds by poly(dimethylsiloxane) (PDMS).
      The proposed flow-through standard water generator eliminates errors associated
      with both losses of analytes to the system surfaces and limited sample volume. In
      addition, the errors caused by partial precipitation or poor dissolution of
      highly hydrophobic analytes during spiking of water when producing calibration
      standards are also eliminated. The target analytes are a range of polycyclic
      aromatic hydrocarbons (PAHs). The results demonstrate that absorption
      partitioning is the predominant mechanism of extraction of analytes into PDMS
      coated fibers for all PAHs investigated regardless of molecular weight. There is
      a strong correlation between determined PDMS/water distribution constants (K(fw))
      and literature K(ow) values for all PAHs.

PMID- 10952558
TI  - Pressurized fluid extraction of nonpolar pesticides and polar herbicides using in
      situ derivatization
AB  - Analysis of polar acidic herbicides has traditionally presented a challenge
      because of their strong adsorption to and ionic interactions with soil. One
      approach which has been successful for extraction of these polar compounds from
      soil is supercritical fluid extraction (SFE) coupled with in situ derivatization.
      This technique involves the addition of common derivatization reagents directly
      into the extraction chamber, where the acid herbicides are derivitized to
      extractable esters or ethers. This study describes the application of an in situ
      derivatization technique to pressurized fluid extraction (PFE) for the herbicides
      2,4-D, 2,4,5-T, dicamba, silvex, trichlopyr, and bentazone. The efficiency of in
      situ derivatization PFE for these analytes is compared with a conventional basic
      extraction method followed by ex situ derivatization. The variables of
      temperature, pressure, static extraction time, and derivatization-reagent amount
      were optimized for recovery of these analytes from soil. Average recovery for
      these six analytes was 107% for in situ derivatization PFE from spiked sand, 93%
      for the same method from a high-concentration spiked soil (50 mg/kg), and 68% for
      the optimized in situ derivatization PFE method from low-concentration soil (0.5
      mg/kg). The in situ derivatization PFE method has substantial advantages of
      simplicity of methodology and reduction in extraction time compared with the
      conventional technique. A second in situ derivatization PFE strategy was
      investigated using sodium EDTA in the extraction chamber for the extraction of
      2,4-D from soil. Preliminary results demonstrate improved recovery with the use
      of Na4EDTA. Extraction efficiency of PFE for nonpolar organochlorine insecticides
      and slightly polar triazine herbicides from soil is also presented and compared
      with that of Soxhlet extraction.

PMID- 10952559
TI  - Analysis of water contaminants and natural water samples using two-step laser
      mass spectrometry
AB  - The applicability of two-step laser mass spectrometry (L2MS) to the analysis of
      water contaminants and environmental water samples is demonstrated. First, the
      ionization characteristics of a selection of naphthyl and carbamate pesticides
      and of phenol were determined. The ion signal of all compounds increased with
      ionization laser pulse energy, within the investigated range (20-200 microJ). Ion
      yields relative to an internal standard, benz[alanthracene, reached 30% for
      naphthyl pesticides ionized at 225 nm and 2-8% at 266 nm. At 266 nm, similar
      relative ion yields were found for phenol. Carbamate pesticides showed lower
      relative ion yields at all wavelengths, by a factor of approximately 10-100, but
      higher relative ion yields, on the order of 1%, were obtained when using short
      (ps) laser pulses for ionization. These data allow one to estimate the detection
      limits of these analytes in a variety of matrixes once they are known for one of
      the compounds. Second, the quantitative analysis of carbaryl, phenol, and
      polycyclic aromatic hydrocarbons in rainwater is demonstrated. The aqueous
      samples were frozen to permit direct L2MS analysis of organic pollutants without
      tedious sample preparation. Detection limits were in the low-microgram per liter
      concentration range and recoveries of phenol from spiked rainwater samples were
      above 90%. The specific advantages are exemplified with the investigation of
      dynamic washout processes of atmospheric organic pollutants with a resolution of
      0.01 mm of precipitation.

PMID- 10952560
TI  - Single-molecule analysis of DNA immobilized on microspheres.
AB  - The formation and analysis of single molecules of fluorescently labeled DNA
      immobilized on polystyrene microspheres is described. Analysis by confocal
      fluorescence microscopy revealed single-step photobleaching, characteristic of a
      single fluorophore. Microspheres provide a means of locating single molecules by
      bright-field microscopy, prior to single-molecule detection. This allows the
      interrogation of single molecules without suffering the limitations of premature
      photobleaching. Statistical analysis of fluorescence intensities for >100
      microspheres suggests attachment of DNA to micropsheres to be consistent with
      Poisson statistics.

PMID- 10952562
TI  - Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in
      Pseudomonas aeruginosa.
AB  - To test the possibility that MexX-MexY, a new set of efflux system components, is
      associated with OprM and contributes to intrinsic resistance in Pseudomonas
      aeruginosa, we constructed a series of isogenic mutants lacking mexXY and/or
      mexAB and/or oprM from a laboratory strain PAO1, and examined their
      susceptibilities to ofloxacin, tetracycline, erythromycin, gentamicin, and
      streptomycin. Loss of either MexXY or OprM from the MexAB-deficient mutant
      increased susceptibility to all agents tested, whereas loss of MexXY from the
      MexAB-OprM-deficient mutant caused no change in susceptibility. Introduction of
      an OprM expression plasmid decreased the susceptibility of the mexAB-oprM
      deficient-/mexXY-maintaining mutant, yet caused no change in the susceptibility
      of a mexAB-oprM- and mexXY-deficient double mutant. Immunoblot analysis using
      anti-MexX polyclonal rabbit serum generated against synthetic oligopeptides
      detected expression of MexX in the PAO1 cells grown in medium containing
      tetracycline, erythromycin, or gentamicin, although expression of MexX was
      undetectable in the cells incubated in medium without any agent. These results
      suggest that MexXY induced by these agents is functionally associated with
      spontaneously expressed OprM and contributes to the intrinsic resistance to these
      agents.

PMID- 10952561
TI  - Efflux-mediated resistance to fluoroquinolones in gram-negative bacteria.

PMID- 10952563
TI  - IBC-1, a novel integron-associated class A beta-lactamase with extended-spectrum
      properties produced by an Enterobacter cloacae clinical strain.
AB  - A transferable beta-lactamase produced by a multidrug-resistant clinical isolate
      of Enterobacter cloacae was studied. The bla gene was carried by a large (>80-kb)
      transmissible plasmid. Nucleotide sequence analysis of cloned fragments revealed
      that it was part of a gene cassette carried by a class 1 integron along with
      other resistance genes, including aac(6')-Ib. The encoded beta-lactamase,
      designated IBC-1, was a novel class A enzyme that hydrolyzed ceftazidime and
      cefotaxime and was inhibited by tazobactam and, to a lesser extent, by
      clavulanate. Also, imipenem exhibited potent inhibitory activity against IBC-1.
      The enzyme consisted of 287 amino acid residues, including Ser-237, cysteines at
      positions 69 and 237a, and Arg-244, which may be implicated in its interaction
      with beta-lactams. In amino acid sequence comparisons, IBC-1 displayed the
      highest similarity with the chromosomal penicillinase of Yersinia enterocolitica,
      a carbenicillinase from Proteus mirabilis GN79, the species-specific beta
      lactamases of Klebsiella oxytoca, and the carbapenemase Sme-1. However, a
      phylogenetic association with established beta-lactamase clusters could not be
      conclusively shown.

PMID- 10952564
TI  - In vitro and in vivo activities of nitazoxanide against Clostridium difficile.
AB  - We have used the hamster model of antibiotic-induced Clostridium difficile
      intestinal disease to evaluate nitazoxanide (NTZ), a nitrothiazole benzamide
      antimicrobial agent. The following in vitro and in vivo activities of NTZ in the
      adult hamster were examined and compared to those of metronidazole and
      vancomycin: (i) MICs and minimum bactericidal concentrations (MBCs) against C.
      difficile, (ii) toxicity, (iii) ability to prevent C. difficile-associated
      ileocecitis, and (iv) propensity to induce C. difficile-associated ileocecitis.
      The MICs and MBCs of NTZ against 15 toxigenic strains of C. difficile were
      comparable to those of vancomycin or metronidazole. C. difficile-associated
      ileocecitis was induced with oral clindamycin and toxigenic C. difficile in a
      group of 60 hamsters. Subgroups of 10 hamsters were given six daily intragastric
      treatments of NTZ (15, 7.5, and 3.0 mg/100 g of body weight [gbw]), metronidazole
      (15 mg/100 gbw), vancomycin (5 mg/100 gbw), or saline (1 ml/100 gbw). Animals
      receiving saline died 3 days post-C. difficile challenge. During the treatment
      period, NTZ (>/=7.5 mg/100 gbw), like metronidazole and vancomycin, prevented
      outward manifestations of clindamycin-induced C. difficile intestinal disease.
      Six of ten hamsters on a scheduled dose of 3.0 mg of NTZ/100 gbw survived for the
      complete treatment period. Of these surviving animals, all but three died of C.
      difficile disease by between 3 and 12 days following discontinuation of
      antibiotic therapy. Another group of hamsters received six similar daily doses of
      the three antibiotics, followed by an inoculation with toxigenic C. difficile.
      All of the NTZ-treated animals survived the 15-day postinfection period. Upon
      necropsy, all hamsters appeared normal: there were no gross signs of toxicity or
      C. difficile intestinal disease, nor was C. difficile detected in the cultures of
      the ceca of these animals. By contrast, vancomycin and metronidazole treatment
      induced fatal C. difficile intestinal disease in 20 and 70% of recipients,
      respectively.

PMID- 10952565
TI  - Prophylactic effect of FK463, a novel antifungal lipopeptide, against
      Pneumocystis carinii infection in mice.
AB  - The prophylactic effect of FK463, a new water-soluble echinocandin-like
      lipopeptide with inhibitory activity against 1, 3-beta-D-glucan synthase, against
      Pneumocystis carinii infection was investigated with the severe combined
      immunodeficient (SCID) mouse model. Treatment with FK463, pentamidine, and saline
      only was performed for 6 weeks from the day after the SCID mice were inoculated
      intranasally with infected lung homogenates. FK463 at 0.2 or 1.0 mg/kg of body
      weight, pentamidine at 4 mg/kg, or saline was subcutaneously administered daily
      into the backs of the SCID mice. The effects of the drugs were evaluated by
      detection of P. carinii cysts in mouse lung homogenates by toluidine blue O
      staining, lung histology, and PCR amplification of a P. carinii-specific DNA
      fragment from the lungs. P. carinii cysts were detected in the lungs of all mice
      administered saline. In contrast, no cysts were detected in mice administered
      both doses of FK463 and pentamidine. A specific DNA fragment was amplified from
      all mice administered saline and at least half or more of the mice administered
      FK463 and pentamidine. These results indicate that FK463 acts on cyst wall
      formation but not on trophozoite proliferation and is extremely effective in
      preventing P. carinii-associated pneumonia. These results suggest that FK463 is
      potentially useful as a prophylactic agent against P. carinii infection.

PMID- 10952566
TI  - Sodium lauryl sulfate increases the efficacy of a topical formulation of
      foscarnet against herpes simplex virus type 1 cutaneous lesions in mice.
AB  - The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel
      formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous
      infection has been evaluated in mice. A single application of the gel formulation
      containing 3% foscarnet given 24 h postinfection exerted only a modest effect on
      the development of herpetic skin lesions. Of prime interest, the addition of 5%
      SLS to this gel formulation markedly reduced the mean lesion score. The improved
      efficacy of the foscarnet formulation containing SLS could be attributed to an
      increased penetration of the antiviral agent into the epidermis. In vitro, SLS
      decreased in a concentration-dependent manner the infectivities of herpesviruses
      for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect.
      Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic
      effects, depending on the concentration used. Foscarnet in phosphate-buffered
      saline decreased in a dose-dependent manner the viability of cultured human skin
      fibroblasts. This toxic effect was markedly decreased when foscarnet was
      incorporated into the polymer matrix. The presence of SLS in the gel formulations
      did not alter the viabilities of these cells. The use of gel formulations
      containing foscarnet and SLS could represent an attractive approach to the
      treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir
      resistant strains.

PMID- 10952567
TI  - Characterization of a variant of vga(A) conferring resistance to streptogramin A
      and related compounds.
AB  - A variant of the vga(A) gene (1,575 bp), encoding an ATP-binding cassette protein
      conferring resistance to streptogramin A and related antibiotics, was cloned from
      the chromosome of a Staphylococcus aureus clinical isolate and sequenced. The
      sequence of the variant was similar to that of the vga(A) gene (83.2% identity).
      However, the G+C content of the variant (35.6%) was higher than that of vga(A)
      (29%) and there was no cross hybridization between vga(A) and the variant at high
      stringency (> or =60 degrees C), the highest temperature at which a signal was
      detected being 55 degrees C. Unlike previous reports for vga(A) and vga(B), the
      variant of vga(A) may be present in multiple copies in the genome. These copies
      are chromosomal in some isolates and both chromosomal and plasmid-borne in
      others. Nucleotide sequences hybridizing at 65 degrees C with the vga(A) variant
      were found in all the staphylococcal strains harboring plasmids carrying both
      vga(B) and vat(B), which also encode resistance to streptogramin A.

PMID- 10952569
TI  - A single oral dose of thalidomide enhances the capacity of lymphocytes to secrete
      gamma interferon in healthy humans.
AB  - Thalidomide is increasingly being used as adjuvant therapy for patients with
      mycobacterial and human immunodeficiency virus (HIV) infections. The T-helper
      (Th)1 cytokine-Th2 cytokine balance critically determines the outcomes of these
      diseases. To obtain insight into the effect of thalidomide on the capacity of
      lymphocytes to produce Th1 and Th2 cytokines, six healthy volunteers received an
      oral dose (400 mg) of thalidomide. Before and at 3, 6, and 24 h after ingestion
      of thalidomide, peripheral blood mononuclear cells (PBMCs) were isolated and
      stimulated for 24 h with the T-cell stimulant staphylococcal enterotoxin B (SEB)
      or anti-CD3/CD28. In all six volunteers ingestion of thalidomide was associated
      with enhanced SEB- and anti-CD3/CD28-induced production of the Th1 cytokine gamma
      interferon (P < 0.05) and a decrease in the level of anti-CD3/CD28-induced
      interleukin-5 (IL-5) production (P < 0.05). The levels of IL-2 (Th1) and IL-4
      (Th2) released remained unchanged. These changes were accompanied by an increase
      in the amount of IL-12p40 released by the PBMCs 6 h after ingestion of
      thalidomide (P < 0.05). Thus, a single oral dose of thalidomide causes a Th1-type
      response in healthy humans. This finding offers a potential explanation for the
      positive effect of thalidomide in patients with mycobacterial and HIV infections.

PMID- 10952568
TI  - Contribution of a thickened cell wall and its glutamine nonamidated component to
      the vancomycin resistance expressed by Staphylococcus aureus Mu50.
AB  - Staphylococcus aureus Mu50, which has reduced susceptibility to vancomycin, has a
      remarkably thickened cell wall with an increased proportion of glutamine
      nonamidated muropeptides. In addition, Mu50 had enhanced glutamine synthetase and
      L-glutamine D-fructose-6-phosphate aminotransferase activities, which are
      involved in the cell-wall peptidoglycan synthesis pathway. Furthermore,
      significantly increased levels of incorporation of (14)C-labeled D-glucose into
      the cell wall was observed in Mu50. Unlike a femC mutant S. aureus strain,
      increased levels of production of nonamidated muropeptides in Mu50 was not caused
      by lower levels of glutamine synthetase activity but was considered to be due to
      the glutamine depletion caused by increased glucose utilization by the cell to
      biosynthesize increased amounts of peptidoglycan. After the cells were allowed to
      synthesize cell wall in the absence or presence of glucose and glutamine, cells
      with different cell-wall thicknesses and with cell walls with different levels of
      cross-linking were prepared, and susceptibility testing of these cells
      demonstrated a strong correlation between the cell-wall thickness and the degree
      of vancomycin resistance. Affinity trapping of vancomycin molecules by the cell
      wall and clogging of the outer layers of peptidoglycan by bound vancomycin
      molecules were considered to be the mechanism of vancomycin resistance of Mu50.
      The reduced cross-linking and the increased affinity of binding to vancomycin of
      the Mu50 cell wall presumably caused by the increased proportion of nonamidated
      muropeptides may also contribute to the resistance to some extent.

PMID- 10952571
TI  - Transcriptional analyses of antifungal drug resistance in Candida albicans.
AB  - Oral infections with the pathogenic yeast Candida albicans are one of the most
      frequent and earliest opportunistic infections in human immunodeficiency virus
      infected patients. The widespread use of azole antifungal drugs has led to the
      development of drug-resistant isolates. Several molecular mechanisms that
      contribute to drug resistance have been identified, including increased mRNA
      levels for two types of efflux pump genes: the ATP binding cassette transporter
      CDRs (CDR1 and CDR2) and the major facilitator MDR1. Using Northern blot
      analyses, the expression patterns of these genes have been determined during
      logarithmic and stationary phases of cell growth and during growth in different
      carbon sources in a set of matched susceptible and fluconazole-resistant isolates
      that have been characterized previously. MDR1, CDR1, and CDR2 are expressed early
      during logarithmic growth, CDR4 is expressed late during logarithmic growth, and
      CDR1 is preferentially expressed in stationary-phase cells. There is a small
      decrease in expression of these genes when the cells are grown in carbon sources
      other than glucose. While increased mRNA levels of efflux pump genes are commonly
      associated with azole resistance, the causes of increased mRNA levels have not
      yet been resolved. Southern blot analysis demonstrates that the increased mRNA
      levels in these isolates are not the result of gene amplification. Nuclear run-on
      assays show that MDR1 and CDR mRNAs are transcriptionally overexpressed in the
      resistant isolate, suggesting that the antifungal drug resistance in this series
      is associated with the promoter and trans-acting factors of the CDR1, CDR2, and
      MDR1 genes.

PMID- 10952570
TI  - Phenotypic characterization of pncA mutants of Mycobacterium tuberculosis.
AB  - We examined the correlation of mutations in the pyrazinamidase (PZase) gene
      (pncA) with the pyrazinamide (PZA) resistance phenotype with 60 Mycobacterium
      tuberculosis isolates. PZase activity was determined by the method of Wayne (L.
      G. Wayne, Am. Rev. Respir. Dis. 109:147-151, 1974), and the entire pncA
      nucleotide sequence, including the 74 bp upstream of the start codon, was
      determined. PZA susceptibility testing was performed by the method of proportions
      on modified Middlebrook and Cohn 7H10 medium. The PZA MICs were > or =100
      microg/ml for 37 isolates, 34 of which had alterations in the pncA gene. These
      mutations included missense substitutions for 24 isolates, nonsense substitutions
      for 3 isolates, frameshifts by deletion for 4 isolates, a three-codon insertion
      for 1 isolate, and putative regulatory mutations for 2 isolates. Among 21
      isolates for which PZA MICs were <100 microg/ml, 3 had the same mutation (Thr47-
      >Ala) and 18 had the wild-type sequence. For the three Thr47-->Ala mutants PZA
      MICs were 12.5 microg/ml by the method of proportions on 7H10 agar; two of these
      were resistant to 100 microg of PZA per ml and the third was resistant to 800
      microg of PZA per ml by the BACTEC method. In all, 30 different pncA mutations
      were found among the 37 pncA mutants. No PZase activity was detected in 35 of 37
      strains that were resistant to > or =100 microg of PZA per ml or in 34 of 37 pncA
      mutants. Reduced PZase activity was found in the three mutants with the Thr47-
      >Ala mutation. This study demonstrates that mutations in the pncA gene may serve
      as a reliable indicator of resistance to > or =100 microg of PZA per ml.

PMID- 10952573
TI  - Efficacy of the echinocandin caspofungin against disseminated aspergillosis and
      candidiasis in cyclophosphamide-induced immunosuppressed mice.
AB  - The in vivo efficacy of the echinocandin antifungal caspofungin acetate
      (caspofungin; MK-0991) was evaluated in models of disseminated aspergillosis and
      candidiasis in mice with cyclophosphamide (CY)-induced immunosuppression.
      Caspofungin is a 1, 3-beta-D-glucan synthesis inhibitor efficacious against a
      number of clinically relevant fungi including Aspergillus and Candida species.
      Models of CY-induced transient or chronic leukopenia were used with once daily
      administration of therapy initiated 24 h after microbial challenge. Caspofungin
      was effective in treating disseminated aspergillosis in mice that were
      transiently leukopenic (significant prolongation of survival at doses of > or
      =0.125 mg/kg of body weight and a 50% protective dose [PD(50)] of 0.245 mg/kg/day
      at 28 days after challenge) or chronically leukopenic (50 to 100% survival at
      doses of > or =0.5 mg/kg and PD(50)s ranging from 0.173 to 0.400 mg/kg/day).
      Caspofungin was effective in the treatment and sterilization of Candida
      infections in mice with transient leukopenia with a 99% effective dose based on
      reduction in log(10) CFU of Candida albicans/gram of kidneys of 0.119 mg/kg and
      80 to 100% of the caspofungin-treated mice having sterile kidneys at caspofungin
      doses from 0.25 to 2.0 mg/kg. In Candida-infected mice with chronic leukopenia,
      caspofungin was effective at all dose levels tested (0.25 to 1.0 mg/kg), with the
      log(10) CFU of C. albicans/gram of kidneys of caspofungin-treated mice being
      significantly lower (>99% reduction) than that of sham-treated mice from day 4 to
      day 28 after challenge. Also, 70 to 100% of the caspofungin-treated, chronic
      leukopenic mice had sterile kidneys at caspofungin doses of 0.5 to 1.0 mg/kg from
      day 8 to 28 after challenge. Sterilization of Candida infections by caspofungin
      in the absence of host leukocytes provides compelling in vivo evidence for
      fungicidal activity against C. albicans. Further human clinical trials with
      caspofungin against serious fungal infections are in progress.

PMID- 10952572
TI  - Functional analysis of the active site of a metallo-beta-lactamase proliferating
      in Japan.
AB  - An R-plasmid-mediated metallo-beta-lactamase was found in Klebsiella pneumoniae
      DK4 isolated in Japan in 1991. The nucleotide sequence of its structural gene
      revealed that the beta-lactamase termed DK4 was identical to the IMP-1 metallo
      beta-lactamase which was mediated by a chromosomal gene of Serratia marcescens
      TN9106 isolated in Japan in 1991 (E. Osano et al., Antimicrob. Agents Chemother.
      38:71-78, 1994). The dose effect of DK4 beta-lactamase production on the
      resistance levels indicated a significant contribution of the enzyme to bacterial
      resistance to all the beta-lactams except monobactams. The enzymatic
      characteristics of the DK4 beta-lactamase and its kinetic parameters for nine
      beta-lactams were examined. The DK4 beta-lactamase was confirmed to contain 2 mol
      of zinc per mol of enzyme protein. The apoenzyme that lacked the two zincs was
      structurally unstable, and the activities of only 30% of the apoenzyme molecules
      could be restored by the addition of 1 mM zinc sulfate. The substitution of five
      conserved histidines (His28, His86, His88, His149, His210) and a cysteine
      (Cys168) for an alanine indicated that His86, His88, and His149 served as ligands
      to one of the zincs and that Cys168 played a role as a ligand to the second zinc.
      Both zinc molecules contribute to the enzymatic process. Mutant enzymes that lack
      only one of these retained some activity. Additionally, a conserved aspartic acid
      at position 90 was replaced by asparagine. This mutant enzyme showed an
      approximately 1,000 times lower k(cat) value for cephalothin than that of the
      wild-type enzyme but retained the two zincs even after dialysis against zinc-free
      buffer. The observed effect of pH on the activity suggested that Asp90 functions
      as a general base in the enzymatic process.

PMID- 10952574
TI  - In vitro resistance profile of the human immunodeficiency virus type 1 protease
      inhibitor BMS-232632.
AB  - BMS-232632 is an azapeptide human immunodeficiency virus (HIV) type 1 (HIV-1)
      protease inhibitor that displays potent anti-HIV-1 activity (50% effective
      concentration [EC(50)], 2.6 to 5.3 nM; EC(90), 9 to 15 nM). In vitro passage of
      HIV-1 RF in the presence of inhibitors showed that BMS-232632 selected for
      resistant variants more slowly than nelfinavir or ritonavir did. Genotypic and
      phenotypic analysis of three different HIV strains resistant to BMS-232632
      indicated that an N88S substitution in the viral protease appeared first during
      the selection process in two of the three strains. An I84V change appeared to be
      an important substitution in the third strain used. Mutations were also observed
      at the protease cleavage sites following drug selection. The evolution to
      resistance seemed distinct for each of the three strains used, suggesting
      multiple pathways to resistance and the importance of the viral genetic
      background. A cross-resistance study involving five other protease inhibitors
      indicated that BMS-232632-resistant virus remained sensitive to saquinavir, while
      it showed various levels (0. 1- to 71-fold decrease in sensitivity)-of cross
      resistance to nelfinavir, indinavir, ritonavir, and amprenavir. In reciprocal
      experiments, the BMS-232632 susceptibility of HIV-1 variants selected in the
      presence of each of the other HIV-1 protease inhibitors showed that the
      nelfinavir-, saquinavir-, and amprenavir-resistant strains of HIV-1 remained
      sensitive to BMS-232632, while indinavir- and ritonavir-resistant viruses
      displayed six- to ninefold changes in BMS-232632 sensitivity. Taken together, our
      data suggest that BMS-232632 may be a valuable protease inhibitor for use in
      combination therapy.

PMID- 10952576
TI  - Pharmacokinetics-pharmacodynamics of a sordarin derivative (GM 237354) in a
      murine model of lethal candidiasis.
AB  - Sordarins are a new class of antifungal agents which selectively inhibit fungal
      protein synthesis (FPS) by impairing the function of elongation factor 2. The
      present study investigates possible correlations between sordarin pharmacokinetic
      (PK) properties and therapeutic efficacy, based on a murine model of invasive
      systemic candidiasis, and provides a rationale for dose selection in the first
      study of efficacy in humans. A significant correlation between PK parameters and
      the in vivo activity of GM 237354, taken as a representative FPS inhibitor, was
      demonstrated in a murine model of lethal systemic candidiasis. Area under the
      concentration-time curve (AUC) and maximum concentration of drug in serum
      (C(max)) over 24 h were determined after a single GM 237354 subcutaneous (s.c.)
      dose (50 mg/kg of body weight) in healthy animals (no significant PK changes with
      infection were observed for other sordarin derivatives). These results have been
      used to simulate PK profiles obtained after several doses and/or schedules in
      animal therapy. A PK-pharmacodynamic (PD) parameter such as the time that serum
      drug concentrations remain above the MIC (t > MIC) was also determined. Treatment
      efficacies were evaluated in terms of the area under the survival time curve
      (AUSTC), using Kaplan-Meier survival analysis and in terms of kidney fungal
      burden (log CFU/gram) after s.c. doses of 2.5, 5, 10, 20, and 40 mg/kg every 4,
      8, or 12 h (corresponding to total daily doses of 5 to 240 mg/kg). The results
      show all treatments to significantly prolong survival versus that of infected and
      nontreated controls (P < 0.05). Relationships between simulated PK and PK-PD
      parameters and efficacy were explored. A good correlation independent of the
      dosing interval was observed with AUC (but not C(max) or t > MIC) and both AUSTC
      and kidney burden. Following repeated dosing every 8 h, AUC(50) (AUC at which 50%
      of the maximum therapeutic efficacy is obtained) was estimated as 21.7 and 37.1
      microg. h/ml (total concentrations) for AUSTC and kidney burden using a sigmoid
      E(max) and an inhibitory sigmoid E(max) PK-PD model, respectively. For an
      efficacy target of 90% survival, AUC was predicted as 67 microg. h/ml. We
      conclude that the PK-PD approach is useful for evaluating relationships between
      PK parameters and efficacy in antifungal research. Moreover, the results obtained
      with this approach could be successfully applied to clinical studies.

PMID- 10952575
TI  - Single-dose AmBisome (Liposomal amphotericin B) as prophylaxis for murine
      systemic candidiasis and histoplasmosis.
AB  - AmBisome is a liposomal formulation of amphotericin B that has broad-spectrum
      antifungal activity and greatly reduced toxicity compared to the parent drug. In
      this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to
      20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent
      and immunosuppressed C57BL/6 mice challenged with either Candida albicans or
      Histoplasma capsulatum. Prophylactic efficacy was based on survival and fungal
      burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma
      challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the
      control and Fungizone groups had died. All AmBisome-treated mice survived,
      although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10
      to 12. No spleen CFU were detected in the histoplasma-challenged mice given 10 or
      20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal
      growth and/or death had occurred in all immunosuppressed mice except for four
      mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in
      the spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg. In the
      C. albicans experiment at 7 days postchallenge, all animals in both untreated and
      treated groups were alive with culture-positive kidneys. The kidney fungal
      burdens in AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower
      than those in the Fungizone group and significantly lower than those in the
      untreated control group (P < 0.05). There was a trend toward decreasing fungal
      growth in the kidneys as the dose of AmBisome was increased. In conclusion, these
      results show that a single high dose of AmBisome (5 to 20 mg/kg) had prophylactic
      efficacy in immunocompetent and immunosuppressed murine H. capsulatum and C.
      albicans models.

PMID- 10952577
TI  - Identification and characterization of vanB2 glycopeptide resistance elements in
      enterococci isolated in Scotland.
AB  - Thirty-two vanB glycopeptide-resistant enterococci (28 Enterococcus faecium and 4
      Enterococcus faecalis) were collected from hospitalized patients in Glasgow,
      Edinburgh, Dundee, and Aberdeen, Scotland, and the vanB element in each was
      compared to vanB1 of E. faecalis strain ATCC 51299. HhaI digestion of PCR
      fragments of the vanB ligase gene was used to identify vanB subtypes. All E.
      faecium isolates were vanB2, and all E. faecalis isolates were vanB1. Restriction
      fragment length polymorphism analysis of a 5,180-bp vanS(B)-vanX(B) long-PCR
      fragment of the vanB cluster showed the loss of HaeII restriction sites in
      vanS(B), vanW, and vanX(B) in strains containing a vanB2 ligase gene. Partial
      sequences of genes in the vanB2 cluster for two genomically distinct Scottish
      isolates were >99.8% identical to each other. vanS(B2), vanX(B2), and vanB2
      sequences differed at the nucleotide level from those of vanS(B), vanX(B), and
      vanB by 4.2, 4.6, and 4.8%, respectively. The vanB2 resistance element appears to
      be widespread among VanB glycopeptide-resistant E. faecium strains isolated in
      Scottish hospitals.

PMID- 10952578
TI  - Molecular characterization of the plasma membrane H(+)-ATPase, an antifungal
      target in Cryptococcus neoformans.
AB  - The Cryptococcus neoformans PMA1 gene, encoding a plasma membrane H(+)-ATPase,
      was isolated from a genomic DNA library of serotype A strain ATCC 6352. An open
      reading frame of 3,380 nucleotides contains six introns and encodes a predicted
      protein consisting of 998 amino acids with a molecular mass of approximately 108
      kDa. Plasma membranes were isolated, and the H(+)-ATPase was shown by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis to be slightly larger than the
      S. cerevisiae H(+)-ATPase, consistent with its predicted molecular mass. The
      plasma membrane-bound enzyme exhibited a pH 6.5 optimum for ATP hydrolysis, K(m)
      and V(max) values of 0.5 mM and 3.1 micromol mg(-1) min(-1), respectively, and an
      apparent K(i) for vanadate inhibition of 1.6 microM. ATP hydrolysis in plasma
      membranes and medium acidification by whole cells were inhibited by ebselen, a
      nonspecific H(+)-ATPase antagonist which was also fungicidal. The predicted C.
      neoformans protein is 35% identical to proton pumps of both pathogenic and
      nonpathogenic fungi but exhibits more than 50% identity to PMA1 genes from
      plants. Collectively, this study provides the basis for establishing the
      Cryptococcus H(+)-ATPase as a viable target for antifungal drug discovery.

PMID- 10952579
TI  - Efficacy of oral cochleate-amphotericin B in a mouse model of systemic
      candidiasis.
AB  - Amphotericin B (AMB) remains the principal therapeutic choice for deep mycoses.
      However, its application is limited by toxicity and a route of administration
      requiring slow intravenous injection. An oral formulation of this drug is
      desirable to treat acute infections and provide prophylactic therapy for high
      risk patients. Cochleates are a novel lipid-based delivery system that have the
      potential for oral administration of hydrophobic drugs. They are stable
      phospholipid-cation crystalline structures consisting of a spiral lipid bilayer
      sheet with no internal aqueous space. Cochleates containing AMB (CAMB) inhibit
      the growth of Candida albicans, and the in vivo therapeutic efficacy of CAMB
      administered orally was evaluated in a mouse model of systemic candidiasis. The
      results indicate that 100% of the mice treated at all CAMB doses, including a low
      dosage of 0.5 mg/kg of body weight/day, survived the experimental period (16
      days). In contrast, 100% mortality was observed with untreated mice by day 12.
      The fungal tissue burden in kidneys and lungs was assessed in parallel, and a
      dose-dependent reduction in C. albicans from the kidneys was observed, with a
      maximum 3.5-log reduction in total cell counts at 2.5 mg/kg/day. However,
      complete clearance of the organism from the lungs, resulting in more than a 4-log
      reduction, was observed at the same dose. These results were comparable to a
      deoxycholate AMB formulation administered intraperitoneally at 2 mg/kg/day (P <
      0.05). Overall, these data demonstrate that cochleates are an effective oral
      delivery system for AMB in a model of systemic candidiasis.

PMID- 10952580
TI  - Accumulation of norfloxacin by Bacteroides fragilis.
AB  - The accumulation of norfloxacin by Bacteroides fragilis NCTC 9343 was determined
      by the modified fluorescence method. The time required to achieve a steady-state
      concentration (SSC) after allowing B. fragilis to accumulate norfloxacin in an
      aerobic or an anaerobic environment was approximately 2 min; the SSC achieved in
      air was 90.28 +/- 9.32 ng of norfloxacin/mg (dry weight) of cells, and that
      achieved anaerobically was 98.45 +/- 3.7 ng of norfloxacin/mg (dry weight) of
      cells. Initial rates of accumulation were determined with a range of external
      concentrations, as up to 8 microg/ml the concentration of norfloxacin accumulated
      increased proportionally to the external concentration, 12.13 ng/mg (dry weight)
      of cells per microg of exogenous norfloxacin per ml. At concentrations above 10
      microg/ml no increase in the rate of norfloxacin accumulation was observed. From
      the kinetic data, a Lineweaver-Burk plot calculated a K(m) of 5.03 microg/ml and
      a V(max) of 25.1 ng of norfloxacin/s. With an increase in temperature of between
      0 and 30 degrees C, the concentration of norfloxacin accumulated also increased
      proportionally at 4.722 ng of norfloxacin/mg (dry weight) of cells/ degrees C. At
      low concentrations of glucose (<0.2%; 11 mM), the concentration of norfloxacin
      accumulated was decreased. With the addition of 100 microM carbonyl cyanide m
      chlorophenylhydrazone (CCCP) the mean SSC of norfloxacin was increased to 116 +/-
      7.01 ng of norfloxacin/mg (dry weight) of cells; glucose had no significant
      effect in the presence of CCCP. Magnesium chloride (20 mM) decreased the SSC of
      norfloxacin to 40.5 +/- 3.76 ng of norfloxacin per mg (dry weight) of cells.
      These data suggest that the mechanism of accumulation of norfloxacin by B.
      fragilis is similar to that of aerobic bacteria and that the fluoresence
      procedure is suitable for use with an anaerobic bacterium.

PMID- 10952581
TI  - Activities of several antimicrobials against Mycobacterium ulcerans infection in
      mice.
AB  - Mycobacterium ulcerans inoculated into the footpads of mice at 6 x 10(3) CFU was
      shown to have a generation time of 6.5 days when estimated from weekly changes in
      microscopic counts of acid-fast bacilli (AFB) and 7.5 days when calculated from
      actual CFU enumerated on Lowenstein-Jensen egg medium incubated at 32 degrees C.
      Footpads became swollen at week 10 (W10) after infection, and all infected
      control mice were dead at W15 after infection. Daily (5 days/week) treatment with
      100 mg of clarithromycin (CLR)/kg of body weight beginning the day after
      infection prevented swelling of footpads at W10. When initiation of treatment was
      delayed until obvious footpad swelling was observed, there was a reduction in
      both the increase in AFB counts and deterioration of swollen footpads and also a
      prolonged survival of the mice to W18. Mice infected in the hind footpads with 5
      x 10(5) CFU of M. ulcerans were divided into an untreated control group and six
      treatment groups that received one of the following therapies for 8 weeks: 100 mg
      of CLR/kg, 25 mg of minocycline (MIN)/kg, 50 mg of sparfloxacin (SPX)/kg, 10 mg
      of rifampin (RIF)/kg, 10 mg of rifabutin (RBT)/kg, or 100 mg of amikacin
      (AMK)/kg. After completion of therapy, treated animals were observed for an
      additional 17 weeks. All control mice and mice treated with CLR, MIN, or SPX
      exhibited swollen footpads during the observation period. In contrast, of those
      animals treated with RIF, RBT, or AMK, none had footpad swelling and all
      inoculated cultures done after the W17 observation remained negative. These
      results suggest that RIF, RBT, and AMK may be effective in the treatment of human
      infection with M. ulcerans.

PMID- 10952582
TI  - Potent synergism of the combination of fluconazole and cyclosporine in Candida
      albicans.
AB  - Several types of drugs currently used in clinical practice were screened in vitro
      for their potentiation of the antifungal effect of the fungistatic agent
      fluconazole (FLC) on Candida albicans. These drugs included inhibitors of
      multidrug efflux transporters, antimicrobial agents, antifungal agents, and
      membrane-active compounds with no antimicrobial activity, such as antiarrhythmic
      agents, proton pump inhibitors, and platelet aggregation inhibitors. Among the
      drugs tested in an agar disk diffusion assay, cyclosporine (Cy), which had no
      intrinsic antifungal activity, showed a potent antifungal effect in combination
      with FLC. In a checkerboard microtiter plate format, however, it was observed
      that the MIC of FLC, as classically defined by the NCCLS recommendations, was
      unchanged when FLC and Cy were combined. Nevertheless, if a different reading
      endpoint corresponding to the minimal fungicidal concentration needed to decrease
      viable counts by at least 3 logs in comparison to the growth control was chosen,
      the combination was synergistic (fractional inhibitory concentration index of
      <1). This endpoint fitted to the definition of MIC-0 (optically clear wells) and
      reflected the absence of the trailing effect, which is the result of a residual
      growth at FLC concentrations greater than the MIC. The MIC-0 values of FLC and Cy
      tested alone in C. albicans were >32 and >10 microg/ml, respectively, and
      decreased to 0.5 and 0.625 microg/ml when the two drugs were combined. The
      combination of 0.625 microg of Cy per ml with supra-MICs of FLC resulted in a
      potent antifungal effect in time-kill curve experiments. This effect was
      fungicidal or fungistatic, depending on the C. albicans strain used. Since the Cy
      concentration effective in vitro is achievable in vivo, the combination of this
      agent with FLC represents an attractive perspective for the development of new
      management strategies for candidiasis.

PMID- 10952583
TI  - Characterization of the extended-spectrum beta-lactamase reference strain,
      Klebsiella pneumoniae K6 (ATCC 700603), which produces the novel enzyme SHV-18.
AB  - Klebsiella pneumoniae K6 (ATCC 700603), a clinical isolate, is resistant to
      ceftazidime and other oxyimino-beta-lactams. A consistent reduction in the MICs
      of oxyimino-beta-lactams by at least 3 twofold dilutions in the presence of
      clavulanic acid confirmed the utility of K. pneumoniae K6 as a quality control
      strain for extended-spectrum beta-lactamase (ESBL) detection. Isoelectric
      focusing analysis of crude lysates of K6 demonstrated a single beta-lactamase
      with a pI of 7.8 and a substrate profile showing preferential hydrolysis of
      cefotaxime compared to ceftazidime. PCR analysis of total bacterial DNA from K6
      identified the presence of a bla(SHV) gene. K6 contained two large plasmids with
      molecular sizes of approximately 160 and 80 kb. Hybridization of plasmid DNA with
      a bla(SHV)-specific probe indicated that a bla(SHV) gene was encoded on the 80-kb
      plasmid, which was shown to transfer resistance to ceftazidime in conjugal mating
      experiments with Escherichia coli HB101. DNA sequencing of this bla(SHV)-related
      gene revealed that it differs from bla(SHV-1) at nine nucleotides, five of which
      resulted in amino acid substitutions: Ile to Phe at position 8, Arg to Ser at
      position 43, Gly to Ala at position 238, and Glu to Lys at position 240. In
      addition to the production of this novel ESBL, designated SHV-18, analysis of the
      outer membrane proteins of K6 revealed the loss of the OmpK35 and OmpK37 porins.

PMID- 10952584
TI  - Comparative In vitro activities of ertapenem (MK-0826) against 1,001 anaerobes
      isolated from human intra-abdominal infections.
AB  - By using an agar dilution method, the comparative in vitro activities of
      ertapenem (MK-0826) were studied against 1,001 anaerobes isolated from human
      intra-abdominal infections in 17 countries worldwide. MK-0826 was uniformly
      active against all isolates, including all Bacteroides fragilis group species
      isolates, with the exception of 12 of 61 (20%) strains of Bilophila wadsworthia,
      3 strains of lactobacilli, and 1 isolate of Acidaminococcus fermentans.
      Geographical variation in activity was not observed.

PMID- 10952585
TI  - Therapeutic responses to quinine and clindamycin in multidrug-resistant
      falciparum malaria.
AB  - Therapeutic responses to clindamycin in combination with quinine were assessed in
      adult Thai patients with uncomplicated multidrug-resistant Plasmodium falciparum
      malaria. In total 204 patients were randomized to receive a 7-day oral treatment
      regimen of quinine (Q(7)) either alone (n = 68), in combination with clindamycin
      (Q(7)C(7); n = 68), or in combination with tetracycline (Q(7)T(7); n = 68). All
      patients had uncomplicated recoveries with no serious adverse effects. Fever
      clearance times for both of the two combination regimens (median of 47 h and
      range of 8 to 120 h for Q(7)C(7) and median of 36 h and range of 8 to 117 h for
      Q(7)T(7)) were significantly shorter than that for the Q(7)-only regimen (median,
      56; range, 4 to 152 h) (P = 0.002). Parasite clearance times (overall mean +/-
      standard deviation, 78 +/- 23 h) were not significantly different between the
      three treatment groups (P = 0. 98). The cure rates assessed at 28 days of follow
      up were 100% for Q(7)C(7) and 98% for Q(7)T(7), whereas the cure rate was 87% for
      the Q(7)-only regimen (P < or = 0.04). Clindamycin in combination with quinine is
      a safe and effective treatment for multidrug-resistant P. falciparum malaria.
      This combination may be of particular value in children and pregnant women, in
      whom tetracyclines are contraindicated.

PMID- 10952586
TI  - Antiviral therapy reduces viral burden but does not prevent thymic involution in
      young cats infected with feline immunodeficiency virus.
AB  - The thymus is a major target organ in human immunodeficiency virus type 1 (HIV-1)
      infected children and feline immunodeficiency virus (FIV)-infected young cats (G.
      A. Dean and N. C. Pedersen, J. Virol. 72:9436-9440, 1998; J. L. Heeney, Immunol.
      Today 16:515-520, 1995; S. M. Schnittman et al., Proc. Natl. Acad. Sci. USA
      87:7727-7731, 1990; T. A. Seemayer et al., Hum. Pathol. 15:469-474, 1984; H.-J.
      Shuurn et al., Am. J. Pathol. 134:1329-1338, 1989; J. C. Woo et al., J. Virol.
      71:8632-8641, 1997; J. C. Woo et al., AIDS Res. Hum. Retrovir. 15:1377-1388,
      1999). It is likely that the accelerated disease process in children and cats is
      due to infection of the thymus during the time when generation of naive T
      lymphocytes is needed for development of the mature immune system. Zidovudine
      (ZDV) monotherapy, which is used to prevent and treat perinatal HIV-1 infection
      (R. Sperling, Infect. Dis. Obstet. Gynecol. 6:197-203, 1998), previously had been
      shown to reduce viral burden in FIV-infected young cats (K. A. Hayes et al., J.
      Acquir. Immune Defic. Syndr. 6:127-134, 1993). The purpose of this study was to
      evaluate the effect of drug-induced reduction of viral burden in the thymus on
      virus-mediated thymic involution and peripheral blood CD4 decline using FIV
      infected cats as a model for pediatric HIV-1 infection. Eight-week-old cats were
      randomly assigned to uninfected, saline-treated; uninfected, ZDV-treated; FIV
      infected, saline-treated; and FIV-infected, ZDV-treated groups. Parameters
      measured included blood lymphocyte numbers, viral load in blood and thymic
      tissue, and thymic histopathology. While the viral burden was significantly
      reduced by ZDV monotherapy in peripheral blood lymphocytes, plasma, and thymus,
      thymic lesions were similar for the treated and untreated FIV-infected cats.
      Further, markedly lowering the viral burden did not increase blood CD4 lymphocyte
      numbers or prevent their decline. The data suggest that an inflammatory process
      continued in spite of reduced virus replication. These observations imply that
      reducing virus load and limiting thymic inflammation are separate factors that
      must be addressed when considering therapeutic strategies aimed at preserving
      thymic function.

PMID- 10952587
TI  - Sodium stibogluconate (Pentostam) potentiates oxidant production in murine
      visceral leishmaniasis and in human blood.
AB  - Sodium stibogluconate (Sbb), a leishmanicidal drug, was studied for its in vivo
      effect on the formation of reactive oxygen species (ROS), assessed by
      chemiluminescence (CL) in the whole blood of mice infected with Leishmania
      infantum. Stimulation of ROS formation induced ex vivo by zymosan particles or
      the protein kinase C activator phorbol myristate acetate (PMA) was reduced by
      approximately 25% (P < 0.05) after infection of mice. Treatment of infected mice
      with Sbb (50 to 400 mg/kg of body weight) enhanced the blood CL induced by
      zymosan and PMA (47 to 96%, P < 0.01). The drug potentiation effect also occurred
      in uninfected mice. In vitro treatment of normal human blood with Sbb (1, 10, or
      100 microg/ml) for 1 h primed the CL response to PMA (29 to 54%). The priming
      effect of Sbb was also observed on the production of superoxide by isolated
      polymorphonuclear leukocytes stimulated either by PMA and zymosan or by the
      chemoattractants N-formyl-Met-Leu-Phe and platelet-activating factor. These data
      provide the first evidence of priming of the phagocyte respiratory burst by Sbb.
      This novel property of Sbb may contribute to the drug's leishmanicidal effect.

PMID- 10952588
TI  - Depletion of the squalene synthase (ERG9) gene does not impair growth of Candida
      glabrata in mice.
AB  - Squalene synthase (farnesyl-diphosphate farnesyltransferase, EC 2.5. 1.21) is the
      first committed enzyme of the sterol biosynthesis pathway. Inhibitors of this
      enzyme have been intensively studied as potential antifungal agents. To assess
      the effect of deactivating squalene synthase on the growth of fungi in mice, we
      isolated the squalene synthase (ERG9) gene from the pathogenic fungus Candida
      glabrata and generated strains in which the CgERG9 gene was under the control of
      the tetracycline-regulatable promoter. Depletion of the ERG9 gene by doxycycline
      (DOX), a derivative of tetracycline, decreased the cell viability in laboratory
      media, whereas it did not affect cell growth in mice at all. The growth defect
      caused by DOX in laboratory media was suppressed by the addition of serum.
      Analyses of the sterol composition of the restored cells in serum-containing
      media suggest that the defect of ergosterol biosynthesis can be complemented by
      the incorporation of exogenous cholesterol into the cells. Thus, deactivation of
      squalene synthase did not affect fungal growth in mice, presumably because the
      cells were able to incorporate cholesterol from the serum. These results showed
      that squalene synthase could not be a suitable target of antifungals for the
      treatment of C. glabrata infection.

PMID- 10952589
TI  - Effect of metronidazole on the pathogenicity of resistant Bacteroides strains in
      gnotobiotic mice.
AB  - Metronidazole is widely used to treat protozoan and fungal infections. As an
      antibacterial drug, it is used mainly against anaerobes. Among anaerobes, the
      Bacteroides fragilis group is the most relevant in terms of frequency of recovery
      and antimicrobial resistance patterns. The use of metronidazole and other
      antimicrobial drugs induces morphological changes in this bacterial group. The
      present study investigated in vivo if these morphological modifications were
      accompanied by changes in virulence patterns by using germfree mice
      experimentally challenged with metronidazole-resistant Bacteroides strains before
      and after exposure to metronidazole. It was observed that metronidazole-resistant
      strains were more virulent after contact with the drug, as demonstrated by
      anatomicopathologic data for spleen, liver, and small intestine samples. These
      results suggest that long-term therapy and high metronidazole concentrations
      could interfere with microbial pathogenicity, resulting in changes to host
      bacterium relationships.

PMID- 10952590
TI  - Therapeutic efficacy of liposomal rifabutin in a Mycobacterium avium model of
      infection.
AB  - Liposomal formulations of rifabutin were developed, and the effects of some
      parameters on the incorporation efficiency were studied. The antimycobacterial
      activity of rifabutin incorporated into liposomes prepared with
      phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a
      murine model of infection with a virulent Mycobacterium avium strain (strain
      P1581) and was compared with that of free rifabutin. The influences of the size
      of the liposomal rifabutin formulation, the administered doses, and the treatment
      schedules on the evolution of infection were studied. Two types of treatment
      schedules were assayed: therapeutic and prophylactic. The therapeutic treatment
      started 2 weeks after infection, while the prophylactic treatment began 1 day
      before the experimental infection with mycobacteria. Incorporation of rifabutin
      in liposomes resulted in a significant enhancement of activity against M. avium
      infection compared to that of rifabutin in the free form in both schedules. These
      results demonstrate that liposomal formulations of antibiotics such as rifabutin
      may be effective for the treatment or prophylaxis of infectious diseases.

PMID- 10952591
TI  - Nonylphenolethoxylates as malarial chloroquine resistance reversal agents.
AB  - Malaria-associated morbidity and mortality are increasing because of widespread
      resistance to one of the safest and least expensive antimalarials, chloroquine.
      The availability of an inexpensive agent that is capable of reversing chloroquine
      resistance would have a major impact on malaria treatment worldwide. The
      interaction of nonylphenolethoxylates (NPEs, commercially available synthetic
      surfactants) with drug-resistant Plasmodium falciparum was examined to determine
      if NPEs inhibited the growth of the parasites and if NPEs could sensitize
      resistant parasites to chloroquine. NPEs inhibited the development of the
      parasite when present in the low- to mid-micromolar range (5 to 90 microM),
      indicating that they possess antimalarial activity. Further, the presence of <10
      microM concentrations of NPEs caused the 50% inhibitory concentrations for
      chloroquine-resistant lines to drop to levels (< or =12 nM) observed for
      sensitive lines and generally considered to be achievable with treatment courses
      of chloroquine. Long-chain (>30 ethoxylate units) NPEs were found to be most
      active in P. falciparum, which contrasts with previously observed maximal
      activity of short-chain ( approximately 9 ethoxylate units) NPEs in multidrug
      resistant mammalian cell lines. NPEs may be attractive chloroquine resistance
      reversal agents since they are inexpensive and may be selectively directed
      against P. falciparum without inhibiting mammalian tissue P glycoproteins.
      Antimalarial preparations that include these agents may prolong the effective
      life span of chloroquine and other antimalarials.

PMID- 10952592
TI  - Interactions between triazoles and amphotericin B against Cryptococcus
      neoformans.
AB  - The interaction of amphotericin B (AmB) and azole antifungal agents in the
      treatment of fungal infections is still a controversial issue. A checkerboard
      titration broth microdilution-based method that adhered to the recommendations of
      the National Committee for Clinical Laboratory Standards was applied to study the
      in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the
      new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of
      Cryptococcus neoformans. Synergy, defined as a fractional inhibitory
      concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in
      studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the
      isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0)
      was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC
      AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or
      =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB,
      ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not
      observed. When synergy was not achieved, there was still a decrease, although not
      as dramatic, in the MIC of one or both drugs when they were used in combination.
      To investigate the effects of FLC-AmB combination therapy in vivo, we established
      an experimental model of systemic cryptococcosis in BALB/c mice by intravenous
      injection of cells of C. neoformans 2337, a clinical isolate belonging to
      serotype D against which the combination of FLC and AmB yielded an additive
      interaction in vitro. Both survival and tissue burden studies showed that
      combination therapy was more effective than FLC alone and that combination
      therapy was at least as effective as AmB given as a single drug. On the other
      hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a
      pronounced increase in resistance to subsequent exposures to AmB was observed. In
      particular, killing experiments conducted with nonreplicating cells showed that
      preexposure to FLC abolished the fungicidal activity of the polyene. However,
      this apparent antagonism was not observed in vivo. Rather, when the two drugs
      were used sequentially for the treatment of systemic murine cryptococcosis, a
      reciprocal potentiation was often observed. Our study shows that (i) the
      combination of triazoles and AmB is significantly more active than either drug
      alone against C. neoformans in vitro and (ii) the concomitant or sequential use
      of FLC and AmB for the treatment of systemic murine cryptococcosis results in a
      positive interaction.

PMID- 10952594
TI  - Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection
      in BALB/cA mice.
AB  - Helicobacter pylori infection in humans is associated with chronic type B
      gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of
      carotenoids and vitamin C has been proposed to prevent development of gastric
      malignancies. The aim of this study was to explore if the microalga Haematococcus
      pluvialis rich in the carotenoid astaxanthin and vitamin C can inhibit
      experimental H. pylori infection in a BALB/cA mouse model. Six-week-old BALB/cA
      mice were infected with the mouse-passaged H. pylori strain 119/95. At 2 weeks
      postinoculation mice were treated orally once daily for 10 days (i) with
      different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body
      weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively),
      (ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with
      vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the
      cessation of treatment, and the other five animals were sacrificed 10 days after
      the cessation of treatment. Culture of H. pylori and determination of the
      inflammation score of the gastric mucosae were used to determine the outcome of
      the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed
      significantly lower colonization levels and lower inflammation scores than those
      of untreated or control-meal-treated animals at 1 day and 10 days after the
      cessation of treatment. Lipid peroxidation was significantly decreased in mice
      treated with the astaxanthin-rich algal meal and vitamin C compared with that of
      animals not treated or treated with the control meal. Both astaxanthin-rich algal
      meal and vitamin C showed an inhibitory effect on H. pylori growth in vitro. In
      conclusion, antioxidants may be a new strategy for treating H. pylori infection
      in humans.

PMID- 10952593
TI  - Antimalarial activities of dermaseptin S4 derivatives.
AB  - The hemolytic antimicrobial peptide dermaseptin S4 was recently shown to exert
      antimalarial activity. In this study, we attempted to understand the underlying
      mechanism(s) and identify derivatives with improved antimalarial activity. A
      number of dermaseptin S4 derivatives inhibited parasite growth with a 50%
      inhibitory concentration (IC(50)) in the micromolar range. Among these, the
      substituted S4 analog K(4)K(20)-S4 was the most potent (IC(50) = 0.2 microM),
      while its shorter version, K(4)-S4(1-13)a, retained a considerable potency
      (IC(50) = 6 microM). Both K(4)K(20)-S4 and K(4)-S4(1-13)a inhibited growth of the
      parasites more at the trophozoite stage than at the ring stage. Significant
      growth inhibition was observed after as little as 1 min of exposure to peptides
      and proceeded with nearly linear kinetics. The peptides selectively lysed
      infected red blood cells (RBC) while having a weaker effect on noninfected RBC.
      Thus, K(4)K(20)-S4 lysed trophozoites at concentrations similar to those that
      inhibited their proliferation, but trophozoites were >30-fold more susceptible
      than normal RBC to the lytic effect of K(4)K(20)-S4, the most hemolytic
      dermaseptin. The same trend was observed with K(4)-S4(1-13)a. The D isomers of
      K(4)K(20)-S4 or K(4)-S4(1-13)a were as active as the L counterparts, indicating
      that antimalarial activity of these peptides, like their membrane-lytic activity,
      is not mediated by specific interactions with a chiral center. Moreover,
      dissipation of transmembrane potential experiments with infected cells indicated
      that the peptides induce damage in the parasite's plasma membrane. Fluorescence
      confocal microscopy analysis of treated infected cells also indicated that the
      peptide is able to find its way through the complex series of membranes and
      interact directly with the intracellular parasite. Overall, the data showed that
      dermaseptins exert antimalarial activity by lysis of infected cells. Dermaseptin
      derivatives are also able to disrupt the parasite plasma membrane without harming
      that of the host RBC.

PMID- 10952595
TI  - Ofloxacin-loaded liposomes: in vitro activity and drug accumulation in bacteria.
AB  - Different ofloxacin-loaded unilamellar vesicles were prepared by the extrusion
      technique, and their antimicrobial activities were determined in comparison to
      those of the free drug by means of MIC determinations with both American Type
      Culture Collection standards and wild-type bacterial strains (six strains of
      Enterococcus faecalis, seven strains of Escherichia coli, six strains of
      Staphylococcus aureus, and six strains of Pseudomonas aeruginosa). The
      accumulation of ofloxacin and liposome-ofloxacin was measured by determining the
      amount of the drug inside the bacteria as a function of time. Encapsulated
      fluoroquinolone yielded MICs which were at least twofold lower than those
      obtained with the free drug. In particular, liposomes made up of
      dimyristoylphosphatidylcholine-cholesterol-dipalmitoylphosphatidylser ine and
      dimyristoylphosphatidylcholine-cholesterol-dihexadecylphosphate (4:3:4 molar
      ratio) provided the best improvement in antimicrobial activity against the
      various bacterial strains investigated. The liposome formulation produced higher
      intracellular fluoroquinolone concentrations than those achieved simultaneously
      with the free drug in both E. coli and P. aeruginosa.

PMID- 10952596
TI  - Tilmicosin induces apoptosis in bovine peripheral neutrophils in the presence or
      in the absence of Pasteurella haemolytica and promotes neutrophil phagocytosis by
      macrophages.
AB  - Pathogen virulence factors and inflammation are responsible for tissue injury
      associated with respiratory failure in bacterial pneumonia, as seen in the bovine
      lung infected with Pasteurella haemolytica. Tilmicosin is a macrolide antibiotic
      used for the treatment of bovine bacterial pneumonia. Recent evidence suggests
      that tilmicosin-induced neutrophil apoptosis may have anti-inflammatory effects.
      Using bovine leukocytes, we sought to define whether live P. haemolytica affected
      tilmicosin-induced neutrophil apoptosis, assessed the proapoptotic effects of
      tilmicosin in comparison with other drugs, and characterized its impact on
      phagocytic uptake of neutrophils by macrophages. Induction of apoptosis in the
      presence or absence of P. haemolytica was assessed by using an enzyme-linked
      immunosorbent assay for apoptotic nucleosomes. In addition, fluorescent annexin-V
      staining identified externalized phosphatidylserine in neutrophils treated with
      tilmicosin, penicillin, ceftiofur, oxytetracycline, or dexamethasone. Neutrophil
      membrane integrity was assessed by using propidium iodide and trypan blue
      exclusion. As phagocytic clearance of apoptotic neutrophils by macrophages
      contributes to the resolution of inflammation, phagocytosis of tilmicosin-treated
      neutrophils by esterase-positive cultured bovine macrophages was assessed with
      light microscopy and transmission electron microscopy. Unlike bovine neutrophils
      treated with penicillin, ceftiofur, oxytetracycline, or dexamethasone,
      neutrophils exposed to tilmicosin became apoptotic, regardless of the presence or
      absence of P. haemolytica. Tilmicosin-treated apoptotic neutrophils were
      phagocytosed at a significantly greater rate by bovine macrophages than were
      control neutrophils. In conclusion, tilmicosin-induced neutrophil apoptosis
      occurs regardless of the presence or absence of live P. haemolytica, exhibits at
      least some degree of drug specificity, and promotes phagocytic clearance of the
      dying inflammatory cells.

PMID- 10952597
TI  - Dendrimers, a new class of candidate topical microbicides with activity against
      herpes simplex virus infection.
AB  - Dendrimers are large highly branched macromolecules synthesized from a
      polyfunctional core. They have shown a variety of biological properties,
      including, in some instances, antiviral activity. In this study, five dendrimers
      were evaluated for in vitro activity against herpes simplex virus (HSV) types 1
      and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in
      human foreskin fibroblast cells. All of the compounds were active against both
      virus types in the CPE inhibition assay, in which drug was added to the cells
      prior to the addition of virus. Antiviral activity was reduced or lost in the PR
      assays, in which the cells were incubated with the virus before the drug was
      added. The prophylactic efficacy suggested that the dendrimers might have
      potential as topical microbicides, products intended to be applied to the vaginal
      or rectal mucosa to protect against sexually transmitted infections. Three
      dendrimers were evaluated for this application against genital HSV infection in
      mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced
      infection rates when 15 microl of a 100-mg/ml solution was administered
      immediately prior to intravaginal challenge, and the most effective compound, BRI
      2999, provided significant protection even when applied 30 min before challenge.
      This is the first report of microbicidal activity by dendrimers in vivo.

PMID- 10952599
TI  - Concentration-dependent selection of small phenotypic differences in TEM beta
      lactamase-mediated antibiotic resistance.
AB  - In this paper, the first robust experimental evidence of in vitro and in vivo
      concentration-dependent selection of low-level antibiotic-resistant genetic
      variants is described. The work is based on the study of an asymmetric
      competition assay with pairs of isogenic Escherichia coli strains, differing only
      (apart from a neutral chromosomal marker) in a single amino acid replacement in a
      plasmid-mediated TEM-1 beta-lactamase enzyme, which results in the new TEM-12
      beta-lactamase. The mixture was challenged by different antibiotic
      concentrations, both in vitro and in the animal model, and the selective process
      of the variant population was carefully monitored. A mathematical model was
      constructed to test the hypothesis that measured growth and killing rates of the
      individual TEM variants at different antibiotic concentrations could be used to
      predict quantitatively the strength of selection for TEM-12 observed in
      competition experiments at these different concentrations.

PMID- 10952600
TI  - Enhanced reduction of Helicobacter pylori load in precolonized mice treated with
      combined famotidine and urease-binding polysaccharides.
AB  - The present study investigated the effect of a model urease-binding
      polysaccharide in combination with a histamine H(2) receptor antagonist on
      Helicobacter pylori colonization in vivo. Euthymic hairless mice were treated
      daily with dextran sulfate via drinking water and/or famotidine via intragastric
      gavage starting at 1 week postchallenge with a CagA(+) VacA(+) (type 1) strain of
      H. pylori. Treatment of precolonized mice for 2 weeks with dextran sulfate
      combined with famotidine yielded a group mean bacterial load (per 100 mg of
      gastric tissue) of log(10) 1.04 CFU, which was significantly lower than those of
      the famotidine (log(10) 3.35 CFU, P < 0.01) and dextran sulfate (log(10) 2.45
      CFU, P < 0.05) monotherapy groups and the infected nontreated group (log(10) 3.64
      CFU, P < 0.01). Eradication was achieved after 2 weeks of treatment in 50% or
      more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2
      weeks of dextran sulfate) versus none in the monotherapy and positive control
      groups. The enhanced activity of the drug combination may be related to the daily
      pattern of transient acid suppression by famotidine inducing periodic bacterial
      convergence to superficial mucus sites penetrated by dextran sulfate from the
      lumen. Increased urease-dextran sulfate avidity was observed in vitro in the
      presence of famotidine and may partly account for the enhanced activity. With
      potential utility in abbreviating treatment time and eradication of antibiotic
      resistant strains, the use of urease-targeted polysaccharides concurrently with a
      gastric acid inhibitor warrants consideration as an additional component of the
      standard multidrug chemotherapy of H. pylori infection.

PMID- 10952598
TI  - Human immunodeficiency virus type 1 mutations selected in patients failing
      efavirenz combination therapy.
AB  - Efavirenz is a potent and selective nonnucleoside inhibitor of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Nucleotide
      sequence analyses of the protease and RT genes (coding region for amino acids 1
      to 229) of multiple cloned HIV-1 genomes from virus found in the plasma of
      patients in phase II clinical studies of efavirenz combination therapy were
      undertaken in order to identify the spectrum of mutations in plasma-borne HIV-1
      associated with virological treatment failure. A K103N substitution was the HIV-1
      RT gene mutation most frequently observed among plasma samples from patients for
      whom combination therapy including efavirenz failed, occurring in at least 90% of
      cases of efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC)
      treatment failure. V108I and P225H mutations were observed frequently,
      predominantly in viral genomes that also contained other nonnucleoside RT
      inhibitor (NNRTI) resistance mutations. L100I, K101E, K101Q, Y188H, Y188L, G190S,
      G190A, and G190E mutations were also observed. V106A, Y181C, and Y188C mutations,
      which have been associated with high levels of resistance to other NNRTIs, were
      rare in the patient samples in this study, both before and after exposure to
      efavirenz. The spectrum of mutations observed in cases of virological treatment
      failure was similar for patients initially dosed with efavirenz at 200, 400, or
      600 mg once a day and for patients treated with efavirenz in combination with
      indinavir, stavudine, or ZDV-3TC. The proportion of patients carrying NNRTI
      resistance mutations, usually K103N, increased dramatically at the time of
      initial viral load rebound in cases of treatment failure after exposure to
      efavirenz. Viruses with multiple, linked NNRTI mutations, especially K103N-V108I
      and K103N-P225H double mutants, accumulated more slowly following the emergence
      of K103N mutant viruses.

PMID- 10952601
TI  - In vitro antiproliferative effects and mechanism of action of the new triazole
      derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum)
      cruzi.
AB  - We describe the in vitro antiproliferative effects of the new triazole derivative
      UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the
      causative agent of Chagas' disease in Latin America. The compound was found to be
      extremely active against the cultured (epimastigote) form of the parasite,
      equivalent to that present in the reduviid vector, with a MIC of 30 nM, a
      concentration 33-fold lower than that required with the reference compound
      ketoconazole. At that MIC, growth arrest coincided with depletion of the
      parasite's 4,14-desmethyl endogenous sterols (ergosterol, 24-ethylcholesta-5,7,22
      trien-3b-ol, and precursors) and their replacement by methylated sterols
      (lanosterol, 24-methylenedihydrolanosterol, and obtusifoliol), as revealed by
      high-resolution gas chromatography coupled with mass spectrometry. This indicated
      that the primary mechanism of action of UR-9825 was inhibition of the parasite's
      sterol C14alpha demethylase, as seen with other azole derivatives. The
      phospholipid composition of growth-arrested epimastigotes was also altered, when
      compared to controls, with a significant increase in the content of
      phosphatidylethanolamine and phosphatidylserine and a concomitant reduction of
      the content of phosphatidylcholine. The clinically relevant intracellular
      amastigote form, grown in cultured Vero cells at 37 degrees C, was even more
      sensitive to UR-9825, with a MIC of 10 nM, comparable to that for ketoconazole.
      The results showed that UR-9825 is among the most potent azole derivatives tested
      against this parasite and support in vivo studies with this compound.

PMID- 10952602
TI  - Identification of the conjugative mef gene in clinical Acinetobacter junii and
      Neisseria gonorrhoeae isolates.
AB  - The mef gene, originally described for gram-positive organisms and coding for an
      efflux pump, has been identified in clinical isolates of Acinetobacter junii and
      Neisseria gonorrhoeae. These strains could transfer the mef gene at frequencies
      ranging from 10(-6) to 10(-9) into one or more of the following recipients: gram
      negative Moraxella catarrhalis, Neisseria perflava/sicca and Neisseria mucosa and
      gram-positive Enterococcus faecalis. Three Streptococcus pneumoniae strains could
      transfer the mef gene into Eikenella corrodens, Haemophilus influenzae, Kingella
      denitrificans, M. catarrhalis, Neisseria meningitidis, N. perflava/sicca, and N.
      mucosa at similar frequencies. The mef gene can thus be transferred to and
      expressed in a variety of gram-negative recipients.

PMID- 10952604
TI  - Antimicrobial evaluation of N-alkyl betaines and N-alkyl-N, N-dimethylamine
      oxides with variations in chain length.
AB  - Alkyl betaines and alkyl dimethylamine oxides have been shown to have pronounced
      antimicrobial activity when used individually or in combination. Although several
      studies have been conducted with these compounds in combinations, only equimolar
      concentrations of the C(12)/C(12) and C(16)/C(14) chain lengths for the betaine
      and the amine oxide, respectively, have been investigated. This study
      investigates the antimicrobial activity of a wide range of chain lengths (C(8) to
      C(18)) for both the betaine and amine oxide and attempts to correlate their
      micelle-forming capabilities with their biological activity. A broth
      microdilution method was used to determine the MICs of these compounds singly and
      in various molar ratio combinations. Activity against both Staphylococcus aureus
      and Escherichia coli was investigated. Antimicrobial activity was found to
      increase with increasing chain length for both homologous series up to a point,
      exhibiting a cutoff effect at chain lengths of approximately 16 for betaine and
      14 for amine oxide. Additionally, the C(18) oleyl derivative of both compounds
      exhibited activity in the same range as the peak alkyl compounds. Critical
      micelle concentrations were correlated with MICs, inferring that micellar
      activity may contribute to the cutoff effect in biological activity.

PMID- 10952603
TI  - Bactericidal activity of micromolar N-chlorotaurine: evidence for its
      antimicrobial function in the human defense system.
AB  - N-Chlorotaurine, the main representative of long-lived oxidants found in the
      supernatant of stimulated granulocytes, has been investigated systematically with
      regard to its antibacterial activity at different physiological concentrations
      for the first time. N-Chlorotaurine (12.5 to 50 microM) demonstrated a
      bactericidal effect i.e., a 2 to 4 log(10) reduction in viable counts, after
      incubation at 37 degrees C for 6 to 9 h at pH 7.0, which effect was significantly
      enhanced in an acidic milieu (at pH 5. 0), with a 3 to 4 log(10) reduction after
      2 to 3 h. Moreover, bacteria were attenuated after being incubated in N
      chlorotaurine for a sublethal time, as demonstrated with the mouse peritonitis
      model. The supernatant of stimulated granulocytes exhibited similar activity.
      Transmission electron microscopy revealed changes in the bacterial cell membrane
      and cytoplasmic disintegration with both reacting systems, even in the case of a
      mere attenuation. The results of this study suggest a significant bactericidal
      function of N-chlorotaurine and other chloramines during inflammation.

PMID- 10952605
TI  - In vitro activities of a new ketolide, ABT-773, alone and in combination with
      amoxicillin, metronidazole, or tetracycline against Helicobacter pylori.
AB  - The in vitro activity of ABT-773, a new ketolide, was compared with those of
      clarithromycin, amoxicillin, metronidazole, and tetracycline against 15 strains
      of Helicobacter pylori. The MIC of ABT-773 at which 90% of isolates were
      inhibited was 0.25 microg/ml, which was 3 dilutions higher than that of the most
      active agent, clarithromycin. Synergy and antagonism were not seen with any
      combinations. Additive activity was seen with tetracycline, metronidazole, and
      amoxicillin in 100, 60, and 40% of the combinations, respectively.

PMID- 10952606
TI  - Analysis of ciprofloxacin activity against Streptococcus pneumoniae after 10
      years of use in the United States.
AB  - As the most commonly used fluoroquinolone in the United States since 1987,
      ciprofloxacin has exerted the greatest selective pressure on S. pneumoniae and
      provides a valuable marker to evaluate the actual and potential emergence of
      fluoroquinolone resistance in this species. Analysis of susceptibility results
      obtained with 5,640 strains collected from throughout the United States showed
      that only 16 (0.3%) of the isolates demonstrated MICs of > or =4 microg/ml. The
      prevalence of this phenotype was significantly higher (P < 0.05) among penicillin
      resistant populations, among isolates from patients >64 years old, and among
      respiratory isolates. However, >99% of strains had MICs of <4 microg/ml
      regardless of the risk group examined, and the MIC population distributions were
      the same for each risk group. These findings demonstrate that the phenotype of a
      MIC of > or =4 microg/ml remains uncommon after 10 years of ciprofloxacin use;
      however, these findings are no reason to become complacent with regard to
      appropriate use of fluoroquinolones and the need to carefully track resistance
      trends. Equally important is careful analysis of data that result from
      surveillance in terms of risk factors and other associated trends so that
      resistance and susceptibility, and their consequences, are neither over- nor
      underestimated.

PMID- 10952607
TI  - Comparative in vitro activities of ABT-773 against aerobic and anaerobic
      pathogens isolated from skin and soft-tissue animal and human bite wound
      infections.
AB  - We studied the comparative in vitro activities of ABT-773, a new ketolide,
      against 268 aerobic and 148 anaerobic recent isolates from clinical bites using
      an agar dilution method and inocula of 10(4) CFU/spot for aerobes and 10(5) CFU
      for anaerobes. The following are the MIC ranges and MICs at which 90% of isolates
      are inhibited (MIC(90)s) of ABT-773 for various isolates, respectively:
      Pasteurella multocida and Pasteurella septica, 0.125 to 2 and 1 microg/ml; other
      Pasteurella species, 0.125 to 1 and 0.5 microg/ml; Corynebacterium spp., 0.015 to
      0.06 and 0.015 microg/ml; Staphylococcus aureus, 0.03 to 0.06 and 0.06 microg/ml;
      coagulase-negative staphylococci, 0.015 to >32 and 32 microg/ml; streptococci,
      0.015 to 0.03 and 0.03 microg/ml; Eikenella corrodens, 0.25 to 1 and 1 microg/ml;
      and Bergeyella zoohelcum, 0.03 to 0.25 and 0.06 microg/ml. For anaerobes the MIC
      ranges and MIC(90)s of ABT-773 were as follows, respectively: Prevotella
      heparinolytica, 0. 06 to 0.125 and 0.125 microg/ml; Prevotella spp., 0.015 to
      0.125 and 0.06 microg/ml; Porphyromonas spp., 0.015 to 0.03 and 0.015 microg/ml;
      Fusobacterium nucleatum, 0.5 to 8 and 8 microg/ml; other Fusobacterium spp.,
      0.015 to 8 and 0.5 microg/ml; Bacteroides tectum, 0.015 to 0.5 and 0.06
      microg/ml; and Peptostreptococcus spp., 0.015 to 0.25 and 0.03 microg/ml. ABT-773
      was more active than all macrolides tested against S. aureus, E. corrodens, and
      anaerobes, but all compounds were poorly active against F. nucleatum. The
      activity of ABT-773 was within 1 dilution of that of azithromycin against
      Pasteurella spp., and ABT-773 was four- to eightfold more active than
      clarithromycin against Pasteurella spp. ABT-773 may offer a therapeutic
      alternative for bite wound infections.

PMID- 10952608
TI  - Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in
      Staphylococcus sciuri.
AB  - The 16.5-kbp plasmid pSCFS1 from Staphylococcus sciuri mediated combined
      resistance to chloramphenicol and florfenicol. The gene responsible for this
      resistance property, cfr, was cloned and sequenced. The amino acid sequence of
      the Cfr protein revealed no homology to known acetyltransferases or efflux
      proteins involved in chloramphenicol and/or florfenicol resistance or to other
      proteins whose functions are known.

PMID- 10952609
TI  - Activities of imipenem and cephalosporins against clonally related strains of
      Escherichia coli hyperproducing chromosomal beta-lactamase and showing altered
      porin profiles.
AB  - Forty clonally related clinical isolates of Escherichia coli from hospitalized
      patients were resistant to cefoxitin (MICs, >256 microg/ml) and ceftazidime
      (MICs, 32 to 256 microg/ml) and were intermediate or resistant to cefotaxime
      (MICs, 16 to 128 microg/ml) but susceptible to both cefepime (MICs, 0.5 to 2
      microg/ml) and imipenem (MICs, 0.125 to 0.25 microg/ml). Resistance to beta
      lactams was related to high-level production of AmpC beta-lactamase and loss of
      OmpF porin.

PMID- 10952611
TI  - Antimalarial activities of aminooxy compounds.
AB  - Twenty-three aminooxy compounds have been examined for their ability to inhibit
      the growth of the malaria parasite Plasmodium falciparum in vitro. Eight of these
      compounds were found to have 50% inhibitory concentrations less than 10 microM,
      with the best drugs being canaline (the aminooxy analogue of ornithine) and
      CGP51905A at 297 +/- 23.6 nM and 242 +/- 18.8 nM, respectively. Canaline was also
      assayed in combination with the ornithine decarboxylase inhibitor
      difluoromethylornithine, and the two drugs were found to be synergistic in
      antimalarial activity.

PMID- 10952612
TI  - In vitro susceptibilities of 400 Spanish isolates of Neisseria gonorrhoeae to
      gemifloxacin and 11 other antimicrobial agents.
AB  - The in vitro activity of gemifloxacin versus those of 11 other antimicrobial
      agents against 400 strains of Neisseria gonorrhoeae was determined by
      microdilution with supplemented GC agar. A total of 37.5% of the strains were
      beta-lactamase positive. A total of 70 and 6.4% of the beta-lactamase-negative
      strains exhibited intermediate and high-level penicillin resistance,
      respectively. Ceftriaxone and gemifloxacin were the most active drugs (MICs at
      which 90% of isolates are inhibited, 0.01 versus 0.007 microg/ml, respectively),
      with 100% of strains inhibited by 0.12 microg/ml.

PMID- 10952610
TI  - TEM-72, a new extended-spectrum beta-lactamase detected in Proteus mirabilis and
      Morganella morganii in Italy.
AB  - A new natural TEM-2 derivative, named TEM-72, was identified in a Proteus
      mirabilis strain and in a Morganella morganii strain isolated in Italy in 1999.
      Compared to TEM-1, TEM-72 contains the following amino acid substitutions: Q39K,
      M182T, G238S, and E240K. Kinetic analysis showed that TEM-72 exhibits an extended
      spectrum activity, including activity against oxyimino-cephalosporins and
      aztreonam. Expression of bla(TEM-72) in Escherichia coli was capable of
      decreasing the host susceptibility to the above drugs.

PMID- 10952613
TI  - Efficacy of ampicillin plus arbekacin in experimental rabbit endocarditis caused
      by an Enterococcus faecalis strain with high-level gentamicin resistance.
AB  - Enterococcus faecalis LC40 is an ampicillin-susceptible clinical isolate with
      high-level gentamicin resistance due to the aac(6')-Ie-aph(2")-Ia aminoglycoside
      resistance gene. The combination of ampicillin plus arbekacin reduced mean
      bacterial vegetation counts significantly more than ampicillin alone or
      ampicillin plus gentamicin in a rabbit model of aortic-valve endocarditis caused
      by E. faecalis LC40.

PMID- 10952614
TI  - Drug interaction studies of a glucan synthase inhibitor (LY 303366) and a chitin
      synthase inhibitor (Nikkomycin Z) for inhibition and killing of fungal pathogens.
AB  - The interaction between inhibitors of components of the fungal cell wall, glucan
      and chitin, was studied in vitro with the respective synthase enzyme inhibitors
      LY 303366 and nikkomycin Z. With Aspergillus fumigatus synergy was noted for
      inhibition and killing, and synergistic activity was also noted for some isolates
      of other species presently regarded as difficult to treat.

PMID- 10952616
TI  - Trovafloxacin treatment of viridans group Streptococcus experimental
      endocarditis.
AB  - The activity of trovafloxacin was compared with those of vancomycin and
      penicillin in a model of Streptococcus sanguis species group (trovafloxacin MIC,
      0.125 microg/ml) and Streptococcus mitis species group (trovafloxacin MIC, 0.125
      microg/ml) experimental endocarditis. Rabbits with catheter-induced aortic valve
      vegetations were given no treatment, trovafloxacin at 15 mg/kg of body weight
      three times a day (t.i.d.), vancomycin at 15 mg/kg twice a day, or penicillin at
      1. 2 x 10(6) IU t.i.d. After 3 days of treatment, the animals were sacrificed;
      cardiac valve vegetations were aseptically removed and cultured quantitatively.
      Penicillin was as active as vancomycin as measured by in vivo clearance of
      bacteria. Trovafloxacin was less active (P < 0.05) than vancomycin or penicillin
      against S. sanguis species group infection but had similar efficacy against S.
      mitis species group infection. Quinolones, despite MICs in the susceptible range,
      may not be active for serious infections caused by some viridans group
      streptococci.

PMID- 10952615
TI  - Molecular characterization of FOX-4, a new AmpC-type plasmid-mediated beta
      lactamase from an Escherichia coli strain isolated in Spain.
AB  - A clinical strain of Escherichia coli (Ec GCE) displayed resistance to cefoxitin,
      cefotetan, cefotaxime, and ceftazidime. Susceptibility was not restored by the
      addition of clavulanic acid. Two beta-lactamases with apparent pIs of 5.4 and 6.4
      were identified; the beta-lactamase with a pI of 6.4 was transferred by
      conjugation and associated with a 40-kb plasmid. Analysis of the nucleotide
      sequence showed a new ampC beta-lactamase gene that is closely related to those
      encoding the FOX-3, FOX-2, and FOX-1 beta-lactamases but whose product has four
      novel amino acid mutations, at positions 11 (M-->T), 43 (A-->E), 233 (V-->A), and
      280 (Y-->H). This first cephamycinase from Spain was named FOX-4.

PMID- 10952617
TI  - In vitro activity of trovafloxacin compared to those of five antimicrobials
      against mycoplasmas including Mycoplasma hominis and Ureaplasma urealyticum
      fluoroquinolone-resistant isolates that have been genetically characterized.
AB  - The in vitro activity of trovafloxacin against 125 strains of Mycoplasma species
      and Ureaplasma urealyticum, including fluoroquinolone-susceptible and
      fluoroquinolone-resistant species, was compared to those of other
      fluoroquinolones, doxycycline, and erythromycin. The MIC at which 90% of isolates
      are inhibited for all fluoroquinolone-susceptible strains was 0.25 microg/ml.
      Whatever the associated mutations, trovafloxacin exhibited greater activity than
      the other fluoroquinolones tested against fluoroquinolone-resistant Mycoplasma
      hominis and U. urealyticum isolates.

PMID- 10952618
TI  - Activities of antimicrobial agents against intracellular pneumococci.
AB  - Pneumococci can enter and survive inside human lung alveolar carcinoma cells. We
      examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin,
      penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci
      inside and outside cells. We found that moxifloxacin, trovafloxacin, and
      telithromycin were the most active, but only telithromycin killed all
      intracellular organisms.

PMID- 10952619
TI  - Successful trovafloxacin prophylaxis against experimental streptococcal aortic
      valve endocarditis.
AB  - Single-dose trovafloxacin (15 mg/kg given intravenously [i.v.]) and ampicillin
      (40 mg/kg given i.v.) protected 38 and 33% of animals challenged with an
      ampicillin-tolerant strain of Streptococcus oralis, respectively. As a double
      dose regimen, trovafloxacin afforded total protection (100%; P < 0.001 versus
      controls). Trovafloxacin is the first fluoroquinolone effective in preventing
      experimental streptococcal endocarditis.

PMID- 10952620
TI  - In vitro activities of six fluoroquinolones against 250 clinical isolates of
      Mycobacterium tuberculosis susceptible or resistant to first-line
      antituberculosis drugs.
AB  - Two hundred fifty isolates of Mycobacterium tuberculosis were evaluated for
      susceptibility to ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin,
      trovafloxacin, and gemifloxacin (SB-265805). Levofloxacin, ciprofloxacin, and
      grepafloxacin showed the greatest activity (MIC for 90% of strains tested
      [MIC(90)] 1 microg/ml), although ofloxacin also showed good activity, with an
      MIC(90) of 2 microg/ml. Trovafloxacin and gemifloxacin showed lower in vitro
      activity, with MIC(90)s of 64 and 8 microg/ml, respectively.

PMID- 10952621
TI  - Fluconazole penetration into the pancreas.
AB  - Because of antibiotic prophylaxis for necrotizing pancreatitis, the frequency of
      fungal superinfection in patients with pancreatic necrosis is increasing. In this
      study we analyzed the penetration of fluconazole into the human pancreas and in
      experimental acute pancreatitis. In human pancreatic tissues, the mean
      fluconazole concentration was 8.19 +/- 3.38 microg/g (96% of the corresponding
      concentration in serum). In experimental edematous and necrotizing pancreatitis,
      88 and 91% of the serum fluconazole concentration was found in the pancreas.
      These data show that fluconazole penetration into the pancreas is sufficient to
      prevent and/or treat fungal contamination in patients with pancreatic necrosis.

PMID- 10952622
TI  - Use of saliva specimens for monitoring indinavir therapy in human
      immunodeficiency virus-infected patients.
AB  - Indinavir concentrations were determined in plasma and saliva over a random
      period of 4 h. On average, levels in saliva were 70% +/- 38% of the corresponding
      levels in plasma. These findings suggest that saliva might serve as an
      appropriate specimen for monitoring of plasma indinavir levels in patients
      treated with indinavir.

PMID- 10952623
TI  - Anti-toxoplasma activities of antiretroviral drugs and interactions with
      pyrimethamine and sulfadiazine in vitro.
AB  - The anti-Toxoplasma activities of nine antiretroviral drugs were examined in
      vitro. Nucleoside analogs had no effect on parasite growth, whereas ritonavir and
      nelfinavir were inhibitory for Toxoplasma, with 50% inhibitory concentrations of
      5.4 and 4.0 microg/ml, respectively. None of the antiviral drugs affected the
      anti-Toxoplasma activity of pyrimethamine or sulfadiazine.

PMID- 10952624
TI  - Inhibitory effects of plant polyphenoloxidase on colonization factors of
      Streptococcus sobrinus 6715.
AB  - Exogenously added polyphenoloxidase (EC 1.14.18.1), an enzyme which oxidizes
      tyrosine residues and is commonly found in many dietary components, abolished the
      aggregation of Streptococcus sobrinus 6715 by high-molecular-weight dextran. The
      enzyme decreased glucan-binding lectin and/or glucosyltransferase I activities.

PMID- 10952625
TI  - Mutant prevention concentration as a measure of antibiotic potency: studies with
      clinical isolates of Mycobacterium tuberculosis.
AB  - The mutant prevention concentration (MPC) of a C-8-methoxy fluoroquinolone
      exhibited a narrow distribution for 14 genetically diverse clinical isolates of
      Mycobacterium tuberculosis, indicating that results from single-isolate studies
      are likely to be representative. When one isolate was challenged with a variety
      of antituberculosis agents, C-8-methoxy fluoroquinolones were exceptional in
      having MPCs below the maximum concentration attained in serum by use of commonly
      recommended doses.

PMID- 10952627
TI  - Molecular developments in renal tubulopathies.

PMID- 10952626
TI  - Characterization of a genetic element carrying the macrolide efflux gene mef(A)
      in Streptococcus pneumoniae.
AB  - The mef(A) gene from a clinical isolate of Streptococcus pneumoniae exhibiting
      the M-type resistance to macrolides was found to be part of the 7,244-bp
      chromosomal element Tn1207.1, which contained 8 open reading frames. orf2 encodes
      a resolvase/invertase, and orf5 is a homolog of the macrolide-streptogramin B
      resistance gene msr(SA).

PMID- 10952629
TI  - Stamps in paediatrics. Disabilities.

PMID- 10952628
TI  - The molecular background to hypophosphataemic rickets.

PMID- 10952630
TI  - The physical punishment of children.

PMID- 10952631
TI  - Implications of the Crown Report and nurse prescribing.

PMID- 10952632
TI  - Developmental dysplasia of the hip (DDH): an evolving science.

PMID- 10952633
TI  - A prospective study of smoking during pregnancy and SIDS.
AB  - AIMS: To study the association between smoking during pregnancy and sudden infant
      death syndrome (SIDS) using prospectively collected data, making it possible to
      account for a number of potential confounders. DESIGN: Prospective follow up
      study (n = 24 986). RESULTS: The overall rate of SIDS was 0.80 per 1000 live
      births (n = 20). Children of smokers had more than three times the risk of SIDS
      compared with children of non-smokers (OR = 3.5; 95% CI 1.4-8.7), and the risk of
      SIDS increased with the number of cigarettes smoked per day (p < 0.05).
      Adjustment for parity, alcohol, and caffeine intake during pregnancy, maternal
      height and weight before pregnancy, years of school, occupational status, marital
      status, and number of antenatal care visits did not change the results.
      Adjustment for mother's age marginally reduced the risk of SIDS associated with
      smoking (OR = 3.0; 95% CI 1.2-7.3). CONCLUSIONS: Given the prospective nature of
      the study, the number of deaths is small; however, if our results reflect a true
      association between smoking during pregnancy and SIDS, approximately 30-40% of
      all cases of SIDS could be avoided if all pregnant women stopped smoking in a
      population with 30% pregnant smokers. Our study adds to earlier evidence for an
      association between smoking during pregnancy and SIDS. The strengths of the study
      are the possibility to adjust for a number of potential confounders and the fact
      that information about smoking habits during pregnancy was prospectively
      collected.

PMID- 10952635
TI  - Teething again

PMID- 10952634
TI  - Prevalence and aetiology of hypothyroidism in the young.
AB  - AIMS: To define the prevalence of hypothyroid disease in children and young
      people, and describe its aetiology. METHODS: We identified all patients on the
      Medicines Monitoring Unit (MEMO) database in the Tayside region of Scotland who
      had received two or more prescriptions for thyroxine during the study period
      (January 1993 to December 1995). Using this as a surrogate marker of
      hypothyroidism, we calculated the prevalence of hypothyroidism in those aged less
      than 22 years. Main outcome measures were prevalence of thyroxine prescription,
      estimated prevalence of hypothyroidism, and aetiology of the hypothyroidism
      (determined from case records, and biochemistry and immunology databases).
      RESULTS: Of 103,500 residents aged less than 22 years, 140 were identified as
      receiving thyroxine on prescription, giving a population prevalence of 0.135%.
      The ratio of male to female was 1:2.8. Acquired hypothyroidism was the commonest
      aetiology found in 73%, 66% of which had an autoimmune basis. The prevalence of
      congenital hypothyroidism was 0.027%. Seven had received treatment for malignancy
      (two primary thyroid). Fifteen per cent of patients had no record of secondary
      care follow up in Tayside. CONCLUSIONS: The overall prevalence of hypothyroidism
      in young people less than 22 years of age is 0.135%, and in the group aged 11-18
      years it is 0.113%; these values are at least twice those of previous estimates.
      This suggests an increase in autoimmune thyroid disease, similar to the rising
      prevalence of type 1 diabetes, possibly indicating a rising incidence of
      autoimmunity in young people.

PMID- 10952636
TI  - The quality of care and influence of double health care coverage in Catalonia
      (Spain).
AB  - AIMS: To analyse inequalities by social class in children's access to and
      utilisation of health services in Catalonia (Spain), private health insurance
      coverage, and certain aspects of the quality of care received. DESIGN: Cross
      sectional study using data from the 1994 Catalan Health Interview Survey.
      SETTING: Child population of Catalonia. PARTICIPANTS: A representative sample of
      non-institutionalised children younger than 15 years (n = 2433). MAIN OUTCOME
      MEASURES: Health services utilisation, perceived health, type of health insurance
      (only National Health System (NHS) or both NHS and private health insurance), and
      social class. RESULTS: No inequalities by social class were found for the
      utilisation of health care services provided by the NHS among children in most
      need. Double health care coverage does not influence the social pattern of
      visits. Nevertheless, social inequalities still remain in the use of those health
      services provided only partially by the NHS (dentist) and when characteristics of
      the last consultation are taken into account. That is, subjects who paid for a
      private service waited an average of 14.8 minutes less than those whose visit was
      paid for by the NHS only. CONCLUSION: Equitable access and use of medical care
      services in relation to need, regardless of the type of insurance and social
      class of their children and families, has been achieved in this region of Spain;
      differences by social class remain for those services incompletely covered by
      national health insurance and aspects of the quality of care provided.

PMID- 10952637
TI  - Limitations of models used to examine the influence of nutrition during pregnancy
      and adult disease.

PMID- 10952638
TI  - Idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura in children usually a self limiting disorder.
      It may follow a viral infection or immunisation and is caused by an inappropriate
      response of the immune system. About 20-30% of children will fail to remit over
      six months (chronic idiopathic thrombocytopenic purpura). This is more likely in
      older children, especially girls. The disease is reviewed with reference to
      diagnosis, investigation, and management options.

PMID- 10952639
TI  - A pilot randomised controlled trial of medical versus nurse clerking for minor
      surgery.
AB  - BACKGROUND: Nurse led clerking is currently practiced in a growing number of UK
      centres, but there is a paucity of evidence to underpin the safety of this
      innovation. AIM: To assess the safety of nurse led clerking in paediatric day
      case and minor surgery. METHODS: Children aged 3 months to 15 years were randomly
      assigned to clerking by either a nurse or a senior house officer (SHO)
      (resident). All children were then independently reassessed by a specialist
      registrar anaesthetist to provide a "gold standard" against which practitioner
      performance could be judged. RESULTS: In 60 children studied, nurses identified a
      significantly greater proportion of the detectable abnormalities present in the
      sample (p = 0.16). This difference is attributable to nurses' greater accuracy in
      history taking (p = 0.04); no conclusions regarding the comparability of nurses'
      and SHOs' skills in physical examination can be derived from the current study.
      CONCLUSION: Evidence attests to the likelihood of nursing having superior skills
      in history taking to SHOs. Exploration of nursing safety in undertaking physical
      examination, however, requires the conduct of a large scale equivalence study.
      Only then can conclusions be drawn as to whether nurse led physical assessment
      offers children a standard of care equivalent to that which they currently
      receive from SHOs.

PMID- 10952642
TI  - Sunscreen and brown naevi

PMID- 10952640
TI  - HIV infection and in-hospital mortality at an academic hospital in South Africa.
AB  - AIM: To document the impact that rapid increases in HIV infection in hospitalised
      children at Chris Hani Baragwanath Hospital has had on in-hospital mortality.
      METHODS: Hospital discharge summaries from January 1992 to the end of 1996 were
      reviewed. RESULTS: There were 20 733 admissions in the five year period; 7985
      (39%) were tested for HIV. In tested admissions above 15 months of age, 4.9% were
      HIV infected in 1992, increasing to 35% in 1996. Under 15 months of age, 9% of
      tested admissions were positive in 1992, increasing to 46% in 1996. The
      proportion of all hospital deaths occurring in children considered HIV infected
      (ELISA testing together with clinical features if 15 months or younger) increased
      from 6.7% in 1992 to 46. 1% in 1996 (p < 0.001). In-hospital mortality for all
      children increased by 21% from 4.3% in 1992 to 5.2% in 1996. Mortality rates
      declined in uninfected children from 5.4% in 1992 to 4.5% in 1996 (chi(2) trend
      3.3; p = 0.06). CONCLUSION: The mortality rate of children has increased at Chris
      Hani Baragwanath Hospital as a result of HIV infection. Almost half the deaths
      were HIV related in 1996. HIV infection is threatening the advances that have
      been made on child survival in South Africa over the last few decades.

PMID- 10952641
TI  - Outcome of invasive pneumococcal disease: a UK based study. Oxford Pneumococcal
      Surveillance Group.
AB  - METHODS: The records of 106 children aged less than 5 years with invasive disease
      caused by Streptococcus pneumoniae were reviewed. RESULTS: The clinical
      manifestations were meningitis (37%), upper respiratory tract infection (24%),
      pneumonia (19%), and occult bacteraemia (18%). One child died and seven had
      persisting neurological impairment. Five serotypes caused 83% of disease and 92%
      of the serotypes are included in the seven valent conjugate vaccines which are
      undergoing trials. CONCLUSIONS: These data suggest that S pneumoniae infection is
      associated with a low case fatality rate but substantial morbidity in the UK.

PMID- 10952643
TI  - Effects of the supine and prone position on diaphragm thickness in healthy term
      infants.
AB  - BACKGROUND: The physiological basis underlying the decline in the incidence of
      sudden infant death syndrome (SIDS) associated with changing the sleep position
      from prone to supine remains unknown. AIMS: To evaluate diaphragm thickness
      (t(di)) and shortening in healthy term infants in the prone and supine positions
      in order to determine whether changes in body position would affect diaphragm
      resting length and the degree of diaphragm shortening during inspiration.
      METHODS: In 16 healthy term infants, diaphragm thickness at the level of the zone
      of apposition on the right side was measured using ultrasonography. Heart rate
      (HR), breathing frequency (f), and transcutaneous oxyhaemoglobin saturation
      (SaO(2)) were recorded simultaneously during diaphragm imaging with the infants
      in the supine and prone positions during quiet sleep. RESULTS: At end expiratory
      (EEV) and at end inspiratory lung volumes (EIV), t(di) increased significantly in
      the prone position. The change in t(di) during tidal breathing was also greater
      when the infant was prone. SaO(2), HR, and f were not significantly different at
      EEV and at EIV in both positions. CONCLUSION: In healthy term infants, placed in
      the prone position, the diaphragm is significantly thicker and, therefore,
      shorter, both at EEV and EIV. Diaphragm shortening during tidal breathing is
      greater when the infant is prone. In the prone position, the decreased diaphragm
      resting length would impair diaphragm strength, and the additional diaphragm
      shortening during tidal breathing represents added work performed by the
      diaphragm. This may compromise an infant's capacity to respond to stressful
      situations when placed in the prone position and may contribute to the
      association of SIDS with prone position.

PMID- 10952644
TI  - Prevalence of abnormal urinary albumin excretion in adolescents and children with
      insulin dependent diabetes: the MIDAC study. Microalbinuria in Diabetic
      Adolescents and Children (MIDAC) research group.
AB  - OBJECTIVE: To examine the prevalence of microalbuminuria, defined as an albumin
      to creatinine ratio (UAC) equal to or greater than 2 mg/mmol in at least two of
      three early morning urine samples, in adolescents and children with insulin
      dependent diabetes mellitus. DESIGN: Centrally coordinated, cross sectional,
      multicentre study in paediatric diabetes outpatient clinics in the United Kingdom
      and Republic of Ireland. METHODS: Blood and urine samples collected between July
      1997 and July 1998 were analysed at a central reference laboratory for HbA(1C)
      using high performance liquid chromatography, and for urinary albumin and
      creatinine concentrations from which the UAC was derived (mg/mmol). Clinical data
      were collected locally and coordinated centrally. SUBJECTS: Patients, aged
      between 10 and 20 years, with insulin dependent diabetes mellitus for more than a
      year, attending diabetes outpatient clinics. RESULTS: A total of 1007 patients,
      comprising 69% of the eligible population of 1451, provided three early morning
      urine samples. Ninety eight (9.7%) had microalbuminuria using the currently
      accepted screening cut off of UAC >/= 2 mg/mmol in at least two of three early
      morning urine samples. Significantly more girls than boys and significantly more
      pubertal and postpubertal patients had abnormal albumin excretion.
      Microalbuminuria was not associated with raised blood pressure. CONCLUSIONS: A
      prevalence of 9.7% for abnormal UAC was found in a cohort of 1007 children and
      adolescents aged 10-20 years. Thus a tenth of this national sample of young
      people were identified as being at particular risk of microvascular and later
      macrovascular disease.

PMID- 10952645
TI  - Oxalate and calcium excretion in cystic fibrosis.
AB  - BACKGROUND: A patient with cystic fibrosis (CF) and repeated calcium oxalate
      renal stones prompted us to investigate other children for risk factors for this
      recognised complication of CF. METHODS: Twenty four hour urinary excretion of
      calcium, oxalate, and glycolate was measured in children with CF and no symptoms
      of renal tract stones. Normal diet and treatments were continued. RESULTS: In 26
      children (aged 5-15.9 years) oxalate excretion was correlated with age; 14 of 26
      children had oxalate excretion above an age appropriate normal range. There was a
      positive correlation between oxalate excretion and glycolate excretion. Mean
      calcium excretion was 0.06 mmol/kg/24 h with 21 of 24 children having calcium
      excretion below the normal range. CONCLUSIONS: Hyperoxaluria may reflect
      malabsorption although correlation between excretion of oxalate and glycolate
      suggests a portion of the excess oxalate is derived from metabolic processes. The
      hypocalciuria observed here may protect children with CF from renal stones.

PMID- 10952646
TI  - The relationship of genotype to cognitive outcome in galactosaemia.
AB  - AIMS: To evaluate the cognitive outcome of a cohort of children with
      galactosaemia in relation to genotype. METHODS: The cohort was drawn from
      children notified to the British Paediatric Surveillance Unit galactosaemia study
      which ran from 1988 to 1990. Cognitive outcome was assessed using the Wechsler
      Intelligence Scale for Children or the Wechsler Preschool and Primary Scale of
      Intelligence. Parents completed a questionnaire detailing educational status, and
      the attending paediatrician returned a questionnaire regarding age at diagnosis
      and biochemical outcome over the previous two years. RESULTS: A total of 45
      children were genotyped: 30 were homoallelic for the Q188R mutation, the
      remainder being heteroallelic for Q188R with K285N (n = 4), L195P (n = 4), or
      other mutations (n = 7). Psychometric evaluation was available in 34 cases: mean
      full scale IQ was 79, verbal quotient 79, and performance quotient 82. Genotype
      was not related to galactose-1-phosphate (Gal-1-P) concentrations. However,
      children homoallelic for the Q188R mutation had significantly lower IQ scores
      than those who were heteroallelic (73. 6 v 94.8). This difference was independent
      of social and demographic influences and Gal-1-P concentrations over the previous
      two years. CONCLUSIONS: In children with galactosaemia, cognitive outcome appears
      to relate to genotype rather than metabolic control, as reflected by Gal-1-P
      concentrations. The value of measuring Gal-1-P concentrations routinely once
      successfully established on a galactosaemia diet is questionable as
      concentrations do not appear to affect outcome. In the UK population,
      homozygosity for the Q188R mutation is invariably associated with a poor outcome,
      and there is evidence that variability in neurocognitive outcome is at least part
      dependent on allelic heterogeneity.

PMID- 10952647
TI  - A controversial expert witness.

PMID- 10952648
TI  - Hypothyroidism mimicking chronic renal failure in reflux nephropathy.
AB  - An adolescent with a history of pyelonephritis and renal scarring had antireflux
      surgery at the age of 2.5 years. His serum creatinine was high at the age of 14
      years (133 micromol/l; glomerular filtration rate (GFR) 56 ml/min x 1.73 m(2)),
      and reflux nephropathy with chronic renal failure was diagnosed. Because of a
      fall in height velocity, endocrinological investigations were performed six
      months later which showed hypothyroidism caused by autoimmune thyroiditis.
      Substitution with thyroxine was started; renal function improved to normal six
      months later (GFR 108 ml/min x 1.73 m(2)). Metabolic changes of hypothyroidism
      led to a reduction of GFR in this patient and mimicked chronic renal failure.

PMID- 10952649
TI  - Kawasaki disease complicated by renal artery stenosis.
AB  - We report the case of a child who developed severe renovascular hypertension six
      months after acute Kawasaki disease. The hypertension was well controlled with
      enalapril, but there was a gradual decrease in function of the affected kidney.
      The lesion, an ostial stenosis of the right main renal artery, was not amenable
      to percutaneous balloon angioplasty, so was treated with bypass surgery.
      Vasculitis is an important cause of renovascular hypertension in children. This
      case highlights the importance of regular blood pressure monitoring in children
      with a history of systemic vasculitis.

PMID- 10952650
TI  - The abnormal nucleus as a cause of congenital facial palsy.
AB  - BACKGROUND: Congenital facial palsy (CFP) is clinically defined as facial palsy
      present at birth. It is associated with considerable disfigurement and causes
      functional and emotional problems for the affected child. The aetiology of the
      majority of cases however, remains elusive. AIMS: To investigate the role of a
      neuroanatomical abnormality as a cause of unilateral CFP. METHODS: Magnetic
      resonance imaging (MRI) scans were performed on 21 patients with unilateral CFP.
      Fifteen patients had unilateral CFP only; six suffered from syndromes which can
      include unilateral CFP. RESULTS: Of the 15 patients with unilateral CFP only,
      four (27%) had an abnormal nucleus or an abnormal weighting of this area on the
      MRI scan, compared to one (17%) of the remaining six patients. CONCLUSION:
      Developmental abnormalities of the facial nucleus itself constitute an important,
      and previously ignored, cause of monosymptomatic unilateral CFP.

PMID- 10952651
TI  - The use of immunosuppressive and cytotoxic drugs in non-malignant disease.

PMID- 10952652
TI  - Comparison of the pressure time product during synchronous intermittent mandatory
      ventilation and continuous positive airway pressure.
AB  - OBJECTIVE: To compare the effect of continuous positive airway pressure (CPAP)
      with synchronous intermittent mandatory ventilation (SIMV) during weaning, by
      measurement of the pressure time product (PTP). The PTP is an estimate of the
      metabolic work or oxygen consumption of the respiratory muscles. PATIENTS: Forty
      children, median age 14 months (range 1 month to 17 years) were studied
      immediately prior to extubation. METHODS: The PTP, derived from airway pressure
      changes, was measured while the child received SIMV (with or without pressure
      support) and then CPAP. A pneumotachograph was placed between the endotracheal
      tube and ventilator circuit. Its flow signal was used to indicate the beginning
      and end of inspiration. Airway pressure was measured from the pneumotachograph
      and the area subtended by the pressure curve (PTP) calculated using a modified
      Labview programme. RESULTS: The median PTP was significantly lower on SIMV (17.1
      cm H(2)O/sec/min, range 0.4 to 60. 5) compared to on CPAP (32.6 cm H(2)O/sec/min,
      range 0.1 to 116.7), p < 0.001. CONCLUSION: These results suggest SIMV, rather
      than CPAP, may be the more efficacious weaning mode in children, and that the
      time spent on CPAP during weaning should be minimised.

PMID- 10952653
TI  - Comparison of an enzyme immunoassay for the detection of Helicobacter pylori
      antigens in the faeces with the urea breath test.
AB  - BACKGROUND: Current diagnostic tests for Helicobacter pylori are invasive
      (endoscopy) or indirect (urea breath test, serology). AIMS: To evaluate a new
      enzyme immunoassay (EIA) which detects H pylori antigens in faeces, by comparing
      its sensitivity and specificity in children with the (13)C urea breath test
      (UBT). METHODS: A total of 119 children underwent a UBT and provided a faecal
      sample for antigen testing within seven days. After an overnight fast each child
      provided a pretest breath sample, and samples at 30 and 40 minutes after
      ingestion of 100 mg (13)C labelled urea. (13)C enrichment of breath was measured
      by isotope ratio mass spectrometry. Faeces were stored at -70 degrees C until
      antigen testing, using the EIA. Samples were read spectrophotometrically at 450
      nm and results were interpreted using recommended cut offs of optical density
      <0.14 as negative, >/=0.16 as positive, with >/=0.14 and <0. 16 representing
      equivocal results. Sensitivity and specificity were calculated using the
      manufacturer's cut off compared with UBT. RESULTS: Sensitivity and specificity
      were 88% and 82%, respectively. Negative and positive predictive values were 97%
      and 58%. CONCLUSIONS: The EIA is an alternative, non-invasive, and easy to use
      method for the detection of H pylori in children. Its high negative predictive
      value suggests a role in screening out uninfected children.

PMID- 10952654
TI  - Performance characteristics of the polymerase chain reaction assay to confirm
      clinical meningococcal disease.
AB  - BACKGROUND: Confirmation of clinical meningococcal disease (MCD) is essential for
      management of patients, contacts, and outbreaks. Blood and CSF cultures, the
      traditional gold standard diagnostic tests, have been adversely affected by
      preadmission parenteral penicillin and fewer lumbar punctures. Rapid, reliable
      serogroup determination without the need to grow isolates could improve
      laboratory confirmation of MCD. AIMS: To determine performance characteristics of
      the currently available meningococcal polymerase chain reaction (PCR) assays in a
      clinical setting. METHODS: Prospective study of 319 children presenting with a
      suspected diagnosis of MCD (fever and a rash, or suspected bacterial meningitis)
      over a 16 month period. RESULTS: A total of 166 (52% of all) children had
      clinical MCD: diagnosis was confirmed microbiologically in 119 (72%) of these.
      Performance characteristics (sensitivity, specificity, negative predictive value,
      positive predictive value) in confirmation of clinical MCD were respectively (95%
      confidence interval): blood culture 31% (24-38%), 100%, 57% (49-65%), 100%; blood
      PCR 47% (39-55%), 100%, 65% (58-73%), 100%; any test positive 72% (65-79%), 100%,
      77% (70-84%), 100%. CONCLUSIONS: Meningococcal DNA detection in blood or CSF by
      PCR is a useful method of diagnosis of MCD. PCR of peripheral blood performs
      better than blood culture. In a child with clinically suspected MCD, PCR assays,
      bacterial antigen tests, and oropharyngeal swabbing for meningococcal carriage
      should be performed in addition to blood or CSF culture, to improve case
      confirmation.

PMID- 10952656
TI  - Zinc deficiency

PMID- 10952655
TI  - Diagnosis of an ectopic ureter in a girl by differential urine collection after
      administration of desmopressin acetate.

PMID- 10952657
TI  - The new children's hospital handbook 1999

PMID- 10952658
TI  - Cerebral palsies: epidemiology and causal pathways

PMID- 10952659
TI  - Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or
      prostaglandin F(2alpha)-induced periodic contraction of rat uterus.
AB  - In isolated rat uterine strips, adrenomedullin (AM) inhibited the spontaneous
      periodic contraction in a concentration-dependent manner (IC(50)=22.3+/-0.7 nM).
      The inhibitory effect of AM was prevented by either AM(22-52), a putative
      antagonist for AM receptors, or calcitonin gene-related peptide (CGRP)(8-37), a
      putative antagonist for CGRP receptors. AM also attenuated bradykinin (BK)
      induced periodic uterine contraction, which was blocked by AM(22-52) or CGRP(8
      37), whereas AM had no effect on the periodic contraction caused by oxytocin or
      prostaglandin F(2alpha) (PGF(2alpha)). RT-PCR analysis showed that mRNAs for
      calcitonin receptor-like receptor (CRLR), receptor-activity-modifying protein
      (RAMP)1, RAMP2 and RAMP3 were expressed in the rat uterus. These results
      demonstrate that AM selectively inhibits spontaneous and BK-induced periodic
      contraction via activating receptors for AM and CGRP.

PMID- 10952660
TI  - Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal
      cord.
AB  - In the present study we tested the effects of the antihyperalgesic compound
      gabapentin on dorsal horn neurones in adult spinal cord. Slices were taken from
      control and hyperalgesic animals suffering from streptozocin-induced diabetic
      neuropathy. At concentrations up to 100 microM, bath application failed to affect
      the resting membrane properties of dorsal horn neurones taken from both groups of
      animal. In contrast, bath application of gabapentin dramatically reduced the
      magnitude of the excitatory postsynaptic current (EPSC) in neurones taken from
      hyperalgesic animals without altering the magnitude of the EPSC in control
      animals. Using a paired pulse stimulation protocol, together with analysis of
      miniature EPSC's, it was possible to demonstrate that gabapentin mediated these
      effects via a pre-synaptic site of action.

PMID- 10952662
TI  - Cytochrome P450 mono-oxygenase gene expression and protein activity in cultures
      of adult cardiomyocytes of the rat.
AB  - There are a substantial number of drugs acting either directly or indirectly on
      the heart, but surprisingly, little is known about the metabolic capacity of
      heart muscle cells. We therefore investigated the gene expression and protein
      activity of cytochrome P450 isozymes in cultures of adult cardiomyocytes of the
      rat. Semi-quantitative CYP gene expression pattern suggests CYP1A1 and CYP2B1/2
      to be key players in cardiomyocytes and upon treatment with Aroclor 1254
      approximate 4 fold inductions could be observed for both gene families, when
      compared with appropriate controls. The mRNA expression of most genes was
      sustained for prolonged periods of time, e.g. up to 120 h in culture and in the
      case of the CYP3A1 gene an approximate 10 fold induction was observed at the
      higher Aroclor 1254 dose level (10 microM) in 24 h old cultures. The
      constitutively expressed genes, e.g. CYP2C11 and CYP2E1 are expressed throughout
      the entire culture period (5 days) and did not respond to Aroclor 1254 treatment.
      CYP4A1 was mainly expressed in freshly isolated cardiomyocytes of control animals
      and its expression declined rapidly in culture. There was good agreement between
      gene expression and translated protein activity using 7-ethoxyresorufin and
      testosterone as substrates. The data reported herein should foster the routine
      use of freshly isolated and cultivated cardiomyocytes for drug profiling and
      toxicity studies.

PMID- 10952661
TI  - Localization and function of ET-1 and ET receptors in small arteries post
      myocardial infarction: upregulation of smooth muscle ET(B) receptors that
      modulate contraction.
AB  - Endothelin-1 (ET-1) has been implicated as a mediator of increased vascular tone
      during development of heart failure post-myocardial infarction (MI). In the
      present study, expression and pharmacology of ET-1 and its receptors were studied
      in small mesenteric arteries from rats at 5 and 12 weeks after coronary artery
      ligation for induction of MI, or sham-operation. In vessels from sham-operated
      and 5 week post-MI rats preproET-1mRNA, immunoreactive (ir) ET-1, ET(B) receptor
      mRNA and irET(B) receptor were confined to the endothelium, while ET(A) receptor
      mRNA was distributed throughout the media. At 12 weeks post-MI, preproET-1 and
      irET(A) receptor localization was similar but ET(B) receptor mRNA and
      immunoreactivity were detectable in the media, as well as the endothelium. The ET
      1 concentration-response curve (CRC) was progressively shifted to the right in
      pressurized third generation mesenteric arteries from 5 and 12 week post-MI rats
      relative to sham-operated rats, with no change in the maximum. The ET(A) receptor
      antagonist BQ-123 (10(-6) M) induced a rightward shift of the ET-1 CRC in all
      vessels. Desensitization of ET(B) receptors, by exposure to SRTX S6c (3x10(-8)
      M), had no effect on the ET-1 CRC in vessels from 5 week post-MI or sham-op rats
      but induced a leftward shift in vessels from 12 week post-MI rats. These results
      identify the endothelium as the primary site of ET-1 synthesis in small arteries
      and the ET(A) receptor as mediating the effects of ET-1 in these vessels.
      However, ET(B) receptor expression increases in vascular smooth muscle post-MI
      and is linked to mechanisms that inhibit the contractile response to ET-1.

PMID- 10952663
TI  - Effects of BDF 9198 on action potentials and ionic currents from guinea-pig
      isolated ventricular myocytes.
AB  - BDF 9198 (a congener of DPI 201 - 106 and BDF 9148) was found to be a positive
      inotrope on guinea-pig isolated ventricular muscle strips. The effects of BDF
      9198 on action potentials and ionic currents from guinea-pig isolated ventricular
      myocytes were studied using the whole cell patch clamp method. In normal external
      solution, at 37 degrees C, action potential duration at 50% repolarization
      (APD(50)) was 167.4+/-8.36 ms (n=37). BDF 9198 produced a concentration-dependent
      increase in APD(50) (no significant increase at 1x10(-10) M; and APD(50) values
      of 273.03+/-35.8 ms at 1x10(-9) M; n=6, P<0.01 and 694.7+/-86.3 ms at 1x10(-7) M;
      P<0.001, n=7). At higher concentrations in the range tested, BDF 9198 also
      induced early and delayed and after-depolarizations. Qualitative measurements of
      I(Na) with physiological [Na](o) showed prolongation of the current by BDF 9198,
      and the appearance of transient oscillatory inward currents at high
      concentrations. Quantitative recording conditions for I(Na) were established
      using low external [Na] and by making measurements at room temperature. The
      current - voltage relation, activation parameters and time-course of I(Na) were
      similar before and after a partial blocking dose of Tetrodotoxin (TTX, 1 microM),
      despite a 2 fold difference in current amplitude. This suggests that voltage
      clamp during flow of I(Na) was adequately maintained under our conditions.
      Selective measurements of I(Na) at room temperature showed that BDF 9198 induced
      a concentration-dependent, sustained component of I(Na) (I(Late)) and caused a
      slight left-ward shift in the current - voltage relation for peak current. The
      drug-induced I(Late) showed a similar voltage dependence to peak current in the
      presence of BDF 9198. Both peak current and I(Late) were abolished by 30 microM
      TTX and were sensitive to external [Na]. Inactivation of control I(Na) during a
      200 ms test pulse to -30 mV followed a bi-exponential time-course. In addition to
      inducing a sustained current component, BDF 9198 left the magnitude of the fast
      inactivation time-constant unchanged, but increased the magnitude of the slow
      inactivation time-constant. Additional experiments with a longer pulse (1 s)
      raised the possibility that in the presence of BDF 9198, I(Na) inactivation may
      be comprised of more than two phases. No significant effects of 1x10(-6) M BDF
      9198 were observed on the L-type calcium current, or delayed and inward
      rectifying potassium currents measured at 37 degrees C. It is concluded that the
      prolongation of APD(50) by BDF 9198 resulted from selective modulation of I(Na).
      Reduced current inactivation induced a persistent I(Na), increasing the net
      depolarizing current during the action potential. This action of the drug
      indicates a potential for 'QT prolongation' of the ECG. The observation of after
      depolarizations suggests a potential for proarrhythmia at some drug
      concentrations.

PMID- 10952665
TI  - Cytochrome P450 inactivation by serum from humans with a viral infection and
      serum from rabbits with a turpentine-induced inflammation: the role of cytokines.
AB  - Serum from humans with an acute upper respiratory viral infection and from
      rabbits with turpentine-induced inflammation reduce the catalytic activity of
      hepatic cytochrome P450 (P450). The aim of this study was to identify the serum
      mediators responsible for the decrease in P450 activity. Rabbit and human sera
      were fractionated by size exclusion chromatography and the fractions tested for
      their ability to reduce the activity and amount of P450 after 4 h of incubation
      with hepatocytes from turpentine-treated rabbits (H(INF)). Rabbit and human sera
      decreased P450 activity by around 40% without any change in the amount of CYP1A1
      and 1A2 apoproteins. In rabbit serum, the fraction containing proteins of M(r) 23
      15 kDa decreased P450 content by 41%, but did not alter the amount of the
      apoproteins. Anti-IL-6 antibody added to the M(r) 23-15 kDa fraction restored
      P450 content to 97% of control values, while anti-IL-1beta, TNF-alpha and IFN
      gamma antibodies had no effect. Supporting the role of IL-6, incubation of H(INF)
      in the presence of IL-6 for 4 h reduced P450 content by 40%. In human serum, the
      fraction containing proteins of M(r) >95 kDa lowered P450 content by 43% without
      modifying the amounts of CYP1A1/2. Neutralization experiments showed that IFN
      gamma, IL-6, and IL-1beta contributed to the decrease in P450 content. In
      conclusion, the present results demonstrate that IL-6, and IFN-gamma, IL-6 and IL
      1beta are the serum mediators released in vivo by a turpentine-induced
      inflammatory reaction in the rabbit and an upper respiratory viral infection in
      humans, respectively, inactivating hepatic P450.

PMID- 10952664
TI  - Induction of reactive astrocytosis and prevention of motoneuron cell death by the
      I(2)-imidazoline receptor ligand LSL 60101.
AB  - I(2)-imidazoline receptors are mainly expressed on glial cells in the rat brain.
      This study was designed to test the effect of treatment with the I(2)-imidazoline
      selective receptor ligand LSL 60101 [2-(2-benzofuranyl)imidazole] on the
      morphology of astrocytes in the neonate and adult rat brain, and to explore the
      putative neuroprotective effects of this glial response. Short-term (3 days) or
      chronic (7-10 days) treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h)
      enhanced the area covered by astroglial cells in sections of facial motor nucleus
      from neonate rats processed for glial fibrillary acidic protein (GFAP)
      immunostaining. Facial motoneurons surrounded by positive glial cell processes
      were frequently observed in sections of LSL 60101-treated rats. A similar glial
      response was observed in the parietal cortex of adult rats after chronic (10
      days) treatment with LSL 60101 (10 mg kg(-1), i.p. every 12 h). Western-blot
      detection of the specific astroglial glutamate transporter GLT-1, indicated
      increased immunoreactivity after LSL 60101 treatment in the pons of neonate and
      in the parietoccipital cortex of adult rats. In the facial motor nucleus of
      neonate rats, the glial response after LSL 60101 treatment was associated to a
      redistribution of the immunofluorescence of the basic fibroblast growth factor
      (FGF-2) from the perinuclear area of motoneurons to cover most of their
      cytoplasm, suggesting a translocation of this mitogenic and neurotrophic factor
      towards secretion pathways. The neuroprotective potential of the above effects of
      LSL 60101 treatment was tested after neonatal axotomy of facial motor nucleus.
      Treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h from day 0 to day 10 after
      birth) significantly reduced (38%) motoneuron death rate 7 days after facial
      nerve axotomy performed on day 3 after birth. It is concluded that treatment with
      the I(2)-imidazoline selective receptor ligand LSL 60101 provokes
      morphological/biochemical changes in astroglia that are neuroprotective after
      neonatal axotomy.

PMID- 10952666
TI  - Sodium channel isoform-specific effects of halothane: protein kinase C co
      expression and slow inactivation gating.
AB  - The modulatory effect of protein kinase C (PKC) on the response of Xenopus oocyte
      expressed Na channel alpha-subunits to halothane (2-bromo-2-chloro-1,1,1
      trifluroethane) was studied. Na currents through rat skeletal muscle, rat brain
      and human cardiac muscle Na channels were assessed using cell-attached patch
      clamp recordings. PKC activity was increased by co-expression of a constitutively
      active PKC alpha-isozyme. Decay of macroscopic Na currents could be separated
      into fast and slow exponential phases. PKC co-expression alone slowed Na current
      decay in neuronal channels, through enhancement of the amplitude of the slower
      phase of decay. Halothane (1.0 mM) was without effect on any of the three
      isoforms expressed alone but, after co-expression of PKC, there was enhancement
      of Na current decay with reduction in charge movement through skeletal muscle and
      neuronal channels. Cardiac channels were relatively insensitive to halothane.
      Enhanced Na current decay resulted from suppression of the slow phase, without
      effect on the faster phase or on either decay tau. Suppression of Na current
      through skeletal muscle channels was concentration-dependent over the therapeutic
      range and was described by third order reaction kinetics, with an IC(50) of 0.55
      mM. We conclude that the halothane suppresses skeletal muscle and brain Na
      channel activity in this preparation through a reduction in the slow mode of
      inactivation gating, but only after PKC co-expression. Cardiac Na channels were
      relatively insensitive to halothane. The mechanism is likely to involve
      phosphorylation of the channel inactivation gate, although phosphorylation of
      other sites in the channel may account for the isoform specific differences.

PMID- 10952667
TI  - Modulation of cholinergic airway reactivity and nitric oxide production by
      endogenous arginase activity.
AB  - Cholinergic airway constriction is functionally antagonized by agonist-induced
      constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO). Since cNOS
      and arginase, which hydrolyzes L-arginine to L-ornithine and urea, use L-arginine
      as a common substrate, competition between both enzymes for the substrate could
      be involved in the regulation of cholinergic airway reactivity. Using a perfused
      guinea-pig tracheal tube preparation, we investigated the modulation of
      methacholine-induced airway constriction by the recently developed, potent and
      specific arginase inhibitor N(Omega)-hydroxy-nor-L-arginine (nor-NOHA).
      Intraluminal (IL) administration of nor-NOHA caused a concentration-dependent
      inhibition of the maximal effect (E(max)) in response to IL methacholine, which
      was maximal in the presence of 5 microM nor-NOHA (E(max)=31.2+/-1.6% of
      extraluminal (EL) 40 mM KCl-induced constriction versus 51.6+/-2.1% in controls,
      P<0.001). In addition, the pEC(50) (-log(10) EC(50)) was slightly but
      significantly reduced in the presence of 5 microM nor-NOHA. The inhibition of
      E(max) by 5 microM nor-NOHA was concentration-dependently reversed by the NOS
      inhibitor N(Omega)-nitro-L-arginine methyl ester (L-NAME), reaching an E(max) of
      89.4+/-7.7% in the presence of 0.5 mM L-NAME (P<0.01). A similar E(max) in the
      presence of 0.5 mM L-NAME was obtained in control preparations (85.2+/-9.7%,
      n.s.). In the presence of excess of exogenously applied L-arginine (5 mM), 5
      microM nor-NOHA was ineffective (E(max)=33.1+/-5.8 versus 31.1+/-7.5% in
      controls, n.s.). The results indicate that endogenous arginase activity
      potentiates methacholine-induced airway constriction by inhibition of NO
      production, presumably by competition with cNOS for the common substrate, L
      arginine. This finding may represent an important novel regulation mechanism of
      airway reactivity.

PMID- 10952669
TI  - Calcium-pH crosstalks in rat mast cells: cytosolic alkalinization, but not
      intracellular calcium release, is a sufficient signal for degranulation.
AB  - The aim of this work was to study the relationship between intracellular
      alkalinization, calcium fluxes and histamine release in rat mast cells.
      Intracellular alkalinization was induced by nigericin, a monovalent cation
      ionophore, and by NH(4)Cl (ammonium chloride). Calcium cytosolic and
      intracellular pH were measured by fluorescence digital imaging using Fura-2-AM
      and BCECF-AM. In rat mast cells, nigericin and NH(4)Cl induce a dose-dependent
      intracellular alkalinization, a dose-dependent increase in intracellular calcium
      levels by releasing calcium from intracellular pools, and an activation of
      capacitative calcium influx. The increase in both intracellular calcium and pH
      activates exocytosis (histamine release) in the absence of external calcium.
      Under the same conditions, thapsigargin does not activate exocytosis, the main
      difference being that thapsigargin does not alkalinize the cytosol. After
      alkalinization, histamine release is intracellular-calcium dependent. With 2.5 mM
      EGTA and thapsigargin the cell response decreases by 62%. The cytosolic
      alkalinization, in addition to the calcium increase it is enough signal to elicit
      the exocytotic process in rat mast cells.

PMID- 10952668
TI  - Lipopolysaccharide enhances bradykinin-induced signal transduction via activation
      of Ras/Raf/MEK/MAPK in canine tracheal smooth muscle cells.
AB  - Bacterial lipopolysaccharide (LPS) was found to induce inflammatory responses and
      to enhance bronchial hyperreactivity to several contractile agonists. However,
      the implication of LPS in the pathogenesis of bronchial hyperreactivity was not
      completely understood. Therefore, in this study, we investigated the effect of
      LPS on mitogen-activated protein kinase (MAPK) activation associated with
      potentiation of bradykinin (BK)-induced inositol phosphates (IPs) accumulation
      and Ca(2+) mobilization in canine cultured tracheal smooth muscle cells (TSMCs).
      LPS stimulated phosphorylation of p42/p44 MAPK in a time- and concentration
      dependent manner using a Western blot analysis against a specific phosphorylated
      form of MAPK antibody. Maximal stimulation of the p42 and p44 MAPK isoforms
      occurred after 7 min-incubation and the maximal effect was achieved with 100
      microg ml(-1) LPS. Pretreatment of TSMCs with LPS potentiated BK-induced IPs
      accumulation and Ca(2+) mobilization. However, there was no effect on the IPs
      response induced by endothelin-1, 5-hydroxytryptamine, and carbachol. In
      addition, pretreatment with PDGF-BB enhanced BK-induced IPs response. These
      enhancements by LPS and PDGF-BB might be due to an increase in BK B(2) receptor
      density (B(max)) in TSMCs, characterized by competitive inhibition of [(3)H]-BK
      binding using B(1) and B(2) receptor-selective reagents. The enhancing effects of
      LPS and PDGF-BB were attenuated by PD98059, an inhibitor of MAPK kinase (MEK),
      suggesting that the effect of LPS may share a common signalling pathway with PDGF
      BB in TSMCs. Furthermore, overexpression of dominant negative mutants, H-Ras-15A
      and Raf-N4, significantly suppressed p42/p44 MAPK activation induced by LPS and
      PDGF-BB, indicating that Ras and Raf may be required for activation of these
      kinases. These results suggest that the augmentation of BK-induced responses
      produced by LPS might be, at least in part, mediated through activation of
      Ras/Raf/MEK/MAPK pathway in TSMCs.

PMID- 10952670
TI  - Neurotoxic activity of venom from the Australian eastern mouse spider (Missulena
      bradleyi) involves modulation of sodium channel gating.
AB  - Mouse spiders represent a potential cause of serious envenomation in humans. This
      study examined the activity of Missulena bradleyi venom in several in vitro
      preparations. Whilst female M. bradleyi venom at doses up to 0.05 microl ml(-1)
      failed to alter twitch or resting tension in all preparations used, male venom
      (0.02 and 0.05 microl ml(-1)) produced potent effects on transmitter release in
      both smooth and skeletal neuromuscular preparations. In the mouse phrenic nerve
      diaphragm preparation, male M. bradleyi venom (0.02 microl ml(-1)) caused rapid
      fasciculations and an increase in indirectly evoked twitches. Male venom (0.02
      and 0.05 microl ml(-1)) also caused a large contracture and rapid decrease in
      indirectly evoked twitches in the chick biventer cervicis muscle, however had no
      effect on responses to exogenous ACh (1 mM) or potassium chloride (40 mM). In the
      chick preparation, contractile responses to male M. bradleyi venom (0.05 microl
      ml(-1)) were attenuated by (+)-tubocurarine (100 microM) and by tetrodotoxin
      (TTX, 1 microM). Both actions of male M. bradleyi venom were blocked by Atrax
      robustus antivenom (2 units ml(-1)). In the unstimulated rat vas deferens, male
      venom (0.05 microl ml(-1)) caused contractions which were inhibited by a
      combination of prazosin (0.3 microM) and P(2X)-receptor desensitization (with
      alpha,beta-methylene ATP 10 microM). In the rat stimulated vas deferens, male
      venom (0.05 microl ml(-1)) augmented indirectly evoked twitches. Male venom (0.1
      microl ml(-1)) causes a slowing of inactivation of TTX-sensitive sodium currents
      in acutely dissociated rat dorsal root ganglion neurons. These results suggest
      that venom from male M. bradleyi contains a potent neurotoxin which facilitates
      neurotransmitter release by modifying TTX-sensitive sodium channel gating. This
      action is similar to that of the delta-atracotoxins from Australian funnel-web
      spiders.

PMID- 10952671
TI  - Ligand regulation of green fluorescent protein-tagged forms of the human beta(1)-
      and beta(2)-adrenoceptors; comparisons with the unmodified receptors.
AB  - Stable clones of HEK293 cells expressing either FLAG(TM) epitope-tagged, wild
      type human beta(1)- and beta(2)-adrenoceptors or C-terminally green fluorescent
      protein (GFP)-tagged forms of these receptors were established. The binding
      affinity of [(3)H]-dihydroalprenolol and other ligands was little affected by
      addition of GFP to the C-terminal of either receptor. Isoprenaline induced the
      internalisation of both beta(1)-adrenoceptor-GFP and beta(2)-adrenoceptor-GFP and
      following removal of the agonist both constructs were able to recycle to the cell
      surface. The extent of internalisation of beta(2)-adrenoceptor-GFP produced by
      isoprenaline was substantially greater than for beta(1)-adrenoceptor-GFP. C
      terminal addition of GFP slowed markedly the rate of internalization of both the
      beta(1)-adrenoceptor and the beta(2)-adrenoceptor in response to isoprenaline.
      Sustained exposure to isoprenaline (24 h) produced substantially greater levels
      of downregulation of native beta(2)-adrenoceptor compared to beta(2)-adrenoceptor
      GFP although both were equally effectively removed from the plasma membrane.
      Sustained exposure to isoprenaline resulted in a large fraction of beta(2)
      adrenoceptor-GFP becoming trapped in internal vesicles/lysosomes but not
      degraded. Even after sustained exposure to isoprenaline a significant fraction of
      beta(1)-adrenoceptor-GFP remained at the cell surface. These results indicate
      that although GFP tagging of beta-adrenoceptors can provide qualitative visual
      patterns of agonist-induced receptor trafficking and regulation in HEK293 cells
      the quantitative details vary markedly from those obtained with the unmodified
      receptors.

PMID- 10952672
TI  - Single channel analysis of the blocking actions of BIDN and fipronil on a
      Drosophila melanogaster GABA receptor (RDL) stably expressed in a Drosophila cell
      line.
AB  - Single channel recordings were obtained from a Drosophila S2 cell line stably
      expressing the wild-type RDL(ac) Drosophila melanogaster homomer-forming
      ionotropic GABA receptor subunit, a product of the resistance to dieldrin gene,
      RDL: GABA (50 microM) was applied by pressure ejection to outside-out patches
      from S2-RDL cells at a holding potential of -60 mV. The resulting inward current
      was completely blocked by 100 microM picrotoxin (PTX). The unitary current
      voltage relationship was linear at negative potentials but showed slight inward
      rectification at potentials more positive than 0 mV. The reversal potential of
      the current (E(GABA)=-1.4 mV) was close to the calculated chloride equilibrium
      potential. The single channel conductance elicited by GABA was 36 pS. A 71 pS
      conductance channel was also observed when the duration of the pulse, used to
      eject GABA, was longer than 80 ms. The mean open time distribution of the unitary
      events was fitted best by two exponential functions suggesting two open channel
      states. When either 1 microM fipronil or 1 microM BIDN was present in the
      external saline, the GABA-gated channels were completely blocked. When BIDN or
      fipronil was applied at a concentration close to the IC(50) value for suppression
      of open probability (281 nM, BIDN; 240 nM, fipronil), the duration of channel
      openings was shortened. In addition, the blocking action of BIDN resulted in the
      appearance of a novel channel conductance (17 pS). The effects of co-application
      of BIDN and fipronil were examined. Co-application of BIDN (300 nM) with various
      concentrations (100-1000 nM) of fipronil resulted in an additional BIDN-induced
      dose-dependent reduction of the maximum P(o) value. Thus both BIDN and fipronil
      shorten the duration of wild-type RDL(ac) GABA receptor channel openings but
      appear to act at distinct sites.

PMID- 10952673
TI  - ATP-induced [Ca(2+)](i) changes and depolarization in GH3 cells.
AB  - Extracellular ATP is a neurotransmitter and mediates a variety of responses. In
      the endocrine system, there are data suggesting a physiological role for ATP in
      Ca(2+) signalling and hormone secretion. However, the ATP receptor subtype
      involved has not been clearly elucidated in GH3 cells, a rat anterior pituitary
      cell line. BzATP- and ATP-induced [Ca(2+)](i) responses had EC(50) values of 18
      and 651 microM, respectively. The maximal response to ATP was only 59+/-8% of
      that for BzATP. The BzATP-induced [Ca(2+)](i) increase was dependent upon the
      extracellular Ca(2+) concentration. Preincubation with oxidized ATP (oATP) nearly
      abolished the ATP- and BzATP-induced [Ca(2+)](i) increases. Both BzATP and ATP
      induced depolarization in GH3 cells, with EC(50) values of 31 microM and 1 mM,
      respectively. The maximal depolarization to BzATP and ATP were 152+/-21 and 146+/
      16% of that elicited by 30 mM KCl. The rank order of agonist potency for
      [Ca(2+)](i) and depolarization responses was BzATP > > ATP >2-MeSATP and purine
      derivatives such as ADP, AMP, adenosine were ineffective. Neither UTP nor alpha,
      beta-methylene ATP showed any effect. In low-divalent conditions BzATP evoked non
      desensitizing inward currents, which were reversed at approximately 0 mV. This
      nonselective cationic conductance was increased by repeated applications of BzATP
      and the cells became very permeable to NMDG. Longer applications (30 min) of
      BzATP stimulated ethidium bromide influx in low divalent conditions, suggesting
      increased permeability to larger molecules. We also identified the existence of
      P2X(7) mRNA on GH3 cells by using reverse transcriptase (RT)-polymerase chain
      reaction (PCR). These results suggest that the GH3 cells have an endogenous
      P2X(7) receptor and purinergic stimulation may play a potential role in
      neuroendocrine modulation on these cells.

PMID- 10952675
TI  - Ginsenoside-induced relaxation of human bronchial smooth muscle via release of
      nitric oxide.
AB  - Ginsenoside, an extract of Panax ginseng, is an essential constituent of anti
      asthmatic Chinese herbal medicine. To elucidate whether ginsenoside affects
      airway smooth muscle tone and, if so, what the mechanism of action is, we studied
      relaxant responses of human bronchial strips under isometric condition in vitro,
      and directly measured the release of nitric oxide (NO) by an amperometric sensor
      for this molecule. Addition of ginsenoside relaxed the tissues precontracted with
      acetylcholine in a dose-dependent manner, the maximal relaxation and the
      ginsenoside concentration required to produce 50% relaxation being 67+/-8% and
      210+/-29 microg ml(-1), respectively. The relaxant responses to ginsenoside were
      inhibited by N(G)-nitro-L-arginine methylester (L-NAME) and removal of the
      epithelium, but not by N(G)-nitro-D-arginine methylester (D-NAME) or
      tetrodotoxin. This inhibitory effect of L-NAME was reversed by L-arginine but not
      by D-arginine. Addition of ginsenoside to the medium containing bronchial tissues
      dose-dependently increased NO-selective electrical current, and this effect was
      greatly attenuated by the epithelial removal or Ca(2+)-free medium. Ginsenoside
      also increased tissue cyclic GMP contents, an effect that was abolished in the
      presence of L-NAME. It is concluded that ginsenoside induces relaxation of human
      bronchial smooth muscle via stimulation of NO generation predominantly from
      airway epithelium and cyclic GMP synthesis. This action might account for the
      anti-asthmatic effect of Panax ginseng.

PMID- 10952676
TI  - Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries.
AB  - The possible role of the endothelium in modulating responses to human urotensin
      II (U-II) was investigated using isolated segments of rat thoracic aorta, small
      mesenteric artery, left anterior descending coronary artery and basilar artery.
      Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat
      thoracic aorta (EC(50)=3.5+/-1.1 nM, R(max)=103+/-10% of control contraction
      induced by 60 mM KCl and 1 microM noradrenaline). However the contractile
      response was not significantly altered by removal of the endothelium or
      inhibition of nitric oxide synthesis with L-NAME (100 microM). Human U-II did not
      cause relaxation of noradrenaline-precontracted, endothelium-intact rat aortae.
      Human U-II contracted endothelium-intact rat isolated left anterior descending
      coronary arteries (EC(50)=1.3+/-0.8 nM, R(max)=20.1+/-4.9% of control contraction
      induced by 10 microM 5-HT). The contractile response was significantly enhanced
      by removal of the endothelium (R(max)=55.4+/-16.1%). Moreover, human U-II caused
      concentration-dependent relaxation of 5-HT-precontracted arteries, which was
      abolished by L-NAME or removal of the endothelium. No contractile effects of
      human U-II were found in rat small mesenteric arteries. However the peptide
      caused potent, concentration- and endothelium-dependent relaxations of
      methoxamine-precontracted vessels. The relaxant responses were potentiated by L
      NAME (300 microM) but abolished in the additional presence of 25 mM KCl (which
      inhibits the actions of endothelium-derived hyperpolarizing factor). The present
      study is the first to show that human U-II is a potent endothelium-dependent
      vasodilator in some rat resistance vessels, and acts through release of EDHF as
      well as nitric oxide. Our findings have also highlighted clear anatomical
      differences in the responses of different vascular beds to human U-II which are
      likely to be important in determining the overall cardiovascular activity of this
      peptide.

PMID- 10952674
TI  - Serotonin inhibition of the NMDA receptor/nitric oxide/cyclic GMP pathway in
      human neocortex slices: involvement of 5-HT(2C) and 5-HT(1A) receptors.
AB  - The NMDA receptor/nitric oxide (NO)/cyclic GMP pathway and its modulation by 5
      hydroxytryptamine (5-HT) was studied in slices of neocortical samples obtained
      from patients undergoing neurosurgery. The cyclic GMP elevation produced by 100
      microM NMDA was blocked by 100 microM of the NO synthase inhibitor N(G)-nitro-L
      arginine (L-NOARG) or by 10 microM of the soluble guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3,-alpha] quinoxaline-1-one (ODQ). The NMDA effect was
      prevented by 5-HT or by the 5-HT(2) agonist (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)
      2-aminopropane ((+/-)-DOI; EC(50)=22 nM). The (+/-)-DOI inhibition was
      insensitive to the 5-HT(2A) receptor antagonist MDL 100907 or the 5-HT(2B)
      antagonist rauwolscine; it was largely prevented by 1 microM of the non-selective
      5-HT(2C) antagonists mesulergine (5-HT(2A,B,C)), ketanserin (5-HT(2A,C)) or SB
      200646A (5-HT(2B,C)); it was completely abolished by 0.1 microM of the selective
      5-HT(2C) receptor antagonist SB 242084. The NMDA-induced cyclic GMP elevation
      also was potently inhibited by the selective 5-HT(2C) agonist RO 60-0175 and by
      the antidepressant trazodone, both added at 1 microM, in an SB 242084-sensitive
      manner. Finally, the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8
      OH-DPAT; 1 microM) inhibited the NMDA-evoked cyclic GMP response, an effect
      blocked by the selective 5-HT(1A) receptor antagonist WAY 100635. In conclusion,
      the NMDA receptor/NO/cyclic GMP pathway in human neocortex slices can be potently
      inhibited by activation of 5-HT(2C) or 5-HT(1A) receptors.

PMID- 10952677
TI  - Sphingosine-1-phosphate and sphingosylphosphorylcholine constrict renal and
      mesenteric microvessels in vitro.
AB  - Sphingolipids such as sphingosine-1-phosphate (SPP) and
      sphingosylphosphorylcholine (SPPC) can act both intracellularly and at G-protein
      coupled receptors, some of which were cloned and designated as Edg-receptors.
      Sphingolipid-induced vascular effects were determined in isolated rat mesenteric
      and intrarenal microvessels. Additionally, sphingolipid-induced elevations in
      intracellular Ca(2+) concentration were measured in cultured rat aortic smooth
      muscle cells. SPPC and SPP (0.1-100 micromol l(-1)) caused concentration
      dependent contraction of mesenteric and intrarenal microvessels (e.g. SPPC in
      mesenteric microvessels pEC(50) 5.63+/-0.17 and E(max) 49+/-3% of noradrenaline),
      with other sphingolipids being less active. The vasoconstrictor effect of SPPC in
      mesenteric microvessels was stereospecific (pEC(50) D-erythro-SPPC 5.69+/-0.08, L
      threo-SPPC 5.31+/-0.06) and inhibited by pretreatment with pertussis toxin
      (E(max) from 44+/-5 to 19+/-4%), by chelation of extracellular Ca(2+) with EGTA
      and by nitrendipine (E(max) from 40+/-6 to 6+/-1 and 29+/-6%, respectively).
      Mechanical endothelial denudation or NO synthase inhibition did not alter the
      SPPC effects, while indomethacin reduced them (E(max) from 87+/-3 to 70+/-4%).
      SPP and SPPC caused transient increases in intracellular Ca(2+) concentrations in
      rat aortic smooth muscle cells in a pertussis toxin-sensitive manner. Our data
      demonstrate that SPP and SPPC cause vasoconstriction of isolated rat microvessels
      and increase intracellular Ca(2+) concentrations in cultured rat aortic smooth
      muscle cells. These effects appear to occur via receptors coupled to pertussis
      toxin-sensitive G-proteins. This is the first demonstration of effects of SPP and
      SPPC on vascular tone and suggests that sphingolipids may be an hitherto
      unrecognized class of endogenous regulators of vascular tone.

PMID- 10952678
TI  - Sphingosine-1-phosphate reduces rat renal and mesenteric blood flow in vivo in a
      pertussis toxin-sensitive manner.
AB  - Sphingolipids such as sphingosine-1-phosphate (SPP) and
      sphingosylphosphorylcholine constrict isolated rat intrarenal and mesenteric
      microvessels in vitro. The present study investigates their effects on the
      cardiovascular system in vivo in anaesthetized rats. The animals were given
      intravenous or intrarenal arterial bolus injections of sphingolipids (0.1-100
      microg kg(-1)) with subsequent measurements of mean arterial pressure, heart rate
      and renal and mesenteric blood flows (RBF, MBF) using a pressure transducer and
      electromagnetic flow probes, respectively. Intravenous injection of SPP rapidly
      (within 30 s), transiently and dose-dependently reduced RBF (maximally -4.0+/-0.3
      ml min(-1)) and MBF (maximally -1.4+/-0.2 ml min(-1)), without affecting mean
      arterial pressure or heart rate. Other sphingolipids had no significant effect.
      Intrarenal arterial SPP administration caused greater blood flow reductions
      (maximally -6.4+/-0.3 ml min(-1)) than systemic administration. Upon intrarenal
      administration, sphingosylphos- phorylcholine also lowered RBF (maximally -2.8+/
      0.6 ml min(-1)), while the other sphingolipids remained without effect.
      Pretreatment with pertussis toxin (PTX, 10 microg kg(-1)) 3 days before the acute
      experiment abolished the SPP-induced reductions of RBF and MBF. These data
      demonstrate, that SPP is a potent vasoconstrictor in vivo, particularly in the
      renal vasculature, while the other structurally related sphingolipids had little
      if any effects. The PTX-sensitivity strongly suggests that the effects of SPP on
      renal and mesenteric blood flow are mediated by receptors coupled to G(i)-type G
      proteins.

PMID- 10952679
TI  - Effect of genistein on native epithelial tissue from normal individuals and CF
      patients and on ion channels expressed in Xenopus oocytes.
AB  - The flavonoid genistein has been shown to activate a Cl(-) conductance in various
      cell types expressing CFTR. We examined if similar effects can be observed when
      genistein is applied to native ex vivo tissues from human respiratory tract and
      rectum. We further compared the effects when genistein was applied to oocytes of
      Xenopus laevis expressing CFTR. In oocytes, both wtCFTR and DeltaF508-CFTR were
      activated by genistein while both cyclic AMP (K(v)LQT1) and Ca(2+) (SK4)
      activated K(+) channels were inhibited at high concentrations of genistein.
      Biopsies from nasal polyps and rectal mucosa were obtained from normal
      individuals (non-CF) and CF patients and in the presence of amiloride (10
      micromol l(-1); mucosal side) the effects of genistein were assessed using a
      perfused Ussing chamber. In non-CF airway epithelia, genistein (50 micromol l(
      1); mucosal side) increased lumen negative I(sc) but had no additional effects on
      tissues pre-stimulated with IBMX and forskolin (100 micromol l(-1) and 1 micromol
      l(-1); both sides). In non-CF rectal biopsies, in the presence of amiloride (10
      micromol l(-1); mucosal side) and indomethacin (10 micromol l(-1); basolateral
      side), genistein increased lumen negative I(sc) and enabled cholinergic
      (carbachol; CCH, 100 micromol l(-1); basolateral side) stimulation of Cl(-)
      secretion indicating activation of luminal CFTR Cl(-) channels. However, after
      stimulation with IBMX/forskolin, genistein induced opposite effects and
      significantly inhibited CCH activated I(sc). In CF airway and intestinal tissues
      genistein failed to induce Cl(-) secretion. Thus, genistein is able to activate
      luminal CFTR Cl(-) conductance in non-CF tissues and mutant CFTR in oocytes.
      However, additional inhibitory effects on basolateral K(+) conductance and
      missing effects in native CF tissues do not support the use for pharmacological
      intervention in CF.

PMID- 10952680
TI  - The novel Na(+)/Ca(2+) exchange inhibitor KB-R7943 also blocks native and
      expressed neuronal nicotinic receptors.
AB  - We studied the effects of the novel Na(+)/Ca(2+) exchange inhibitor KB-R7943, 2
      [2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate, on the native
      nicotinic receptors present at the bovine adrenal chromaffin cells, as well as on
      rat brain alpha(3)beta(4) and alpha(7) nicotinic acetylcholine receptors (AChRs)
      expressed in Xenopus oocytes. As expected, KB-R7943 blocked the Na(+)-gradient
      dependent (45)Ca(2+) uptake into chromaffin cells (IC(50) of 5.5 microM); but in
      addition, the compound also inhibited the (45)Ca(2+) entry and the increase of
      cytosolic Ca(2+) concentration, [Ca(2+)](c), stimulated by 5 s pulses of ACh
      (IC(50) of 6.5 and 1.7 microM, respectively). In oocytes expressing
      alpha(3)beta(4) and alpha(7) nicotinic AChRs, voltage-clamped at -60 mV, inward
      currents elicited by 1 s pulses of 100 microM ACh (I(ACh)) were blocked by KB
      R7943 with an IC(50) of 0.4 microM and a Hill coefficient of 0.9. Blockade of
      alpha(3)beta(4) currents by KB-R7943 was noncompetitive; moreover, the blocker
      (0.3 microM) became more active as the ACh concentration increased (34 versus 66%
      blockade at 30 microM and 1 mM ACh, respectively). Inhibition of alpha(3)beta(4)
      currents by 0.3 microM KB-R7943 was more pronounced at hyperpolarized potentials.
      If given within the ACh pulse (10 microM), the inhibition amounted to 33, 64 and
      80% in oocytes voltage-clamped at -40, -60 and -100 mV, respectively. The onset
      of blockade was faster and the recovery slower at -100 mV; the reverse was true
      at -40 mV. In conclusion, KB-R7943 is a potent blocker of nicotinic AChRs;
      moreover, it displays many features of an open-channel blocker at the rat brain
      alpha(3)beta(4) AChR. These results should be considered when KB-R7943 is to be
      used to study Ca(2+) homeostasis in cells expressing nicotinic AChRs and the
      Na(+)/Ca(2+) exchanger.

PMID- 10952681
TI  - Characterization of prostanoid receptors mediating actions of the isoprostanes, 8
      iso-PGE(2) and 8-iso-PGF(2alpha), in some isolated smooth muscle preparations.
AB  - We investigated the contracting actions of the isoprostanes (isoPs), 8-iso
      prostaglandin (PG) F(2alpha) and 8-iso-PGE(2), in comparison to the effects of
      the thromboxane (TX) A(2)-mimetic U 46619 and the traditional prostaglandin
      PGE(2) in the isolated rat aorta, isolated rat gastric fundus and the isolated
      guinea-pig ileum. U 46619 and 8-iso-PGF(2alpha) caused contractions in the rat
      aorta and rat gastric fundus in a concentration-dependent manner, whereas these
      agonists showed no effects in the guinea-pig ileum. However, 8-iso-PGE(2) and
      PGE(2) caused contractions in all isolated organs used. The prostanoid TP
      receptor antagonist SQ 29,548 (10 nM) significantly antagonized vasoconstrictions
      induced by the agonists used in the rat aorta. SQ 29,548 at a final concentration
      of 3 microM, but not at lower concentrations, significantly inhibited
      contractions induced by U 46619, 8-iso-PGF(2alpha) and 8-iso-PGE(2) in the rat
      fundus. Responses to PGE(2) were unchanged. The prostanoid EP(1)-receptor
      antagonist SC 51089 (3 microM) significantly inhibited contractions induced by 8
      iso-PGE(2) and PGE(2) in the rat fundus and in the guinea-pig ileum. SC 51089 had
      no effect on responses to any of the agonists tested. Our results show that 8-iso
      PGE(2), in contrast to 8-iso-PGF(2alpha), can also cause contractions by
      activation of the EP(1)-receptors in the rat gastric fundus and the guinea-pig
      ileum. The findings of the present study do not support the existence of a unique
      isoP-receptor in the tissues used.

PMID- 10952683
TI  - Pharmacological characterization of [(3)H]-prostaglandin E(2) binding to the
      cloned human EP(4) prostanoid receptor.
AB  - Prostaglandin (PG) E(2) (PGE(2)) is a potent prostanoid derived from arachidonic
      which can interact with EP(1), EP(2), EP(3) and EP(4) prostanoid receptor
      subtypes. Recombinant human EP(4) receptors expressed in human embryonic kidney
      (HEK-293) cells were evaluated for their binding characteristics using [(3)H]
      PGE(2) and a broad panel of natural and synthetic prostanoids in order to define
      their pharmacological properties. [(3)H]-PGE(2) binding was optimal in 2-[N
      Morpholino]ethanesulphonic acid (MES) buffer (pH 6.0) yielding 98+/-0.7% specific
      binding. The receptor displayed high affinity (K(d)=0.72+/-0.12 nM; n=3) for
      [(3)H]-PGE(2) and interacted with a saturable number of binding sites
      (B(max)=6.21+/-0.84 pmol mg(-1) protein). In competition studies, PGE(2)
      (K(i)=0.75+/-0.03 nM; n=12) and PGE(1) (K(i)=1.45+/-0.24 nM; n=3) displayed high
      affinities, as did two derivatives of PGE(1), namely 11-deoxy-PGE(1) (K(i)=1.36+/
      0.34 nM) and 13,14-dihydro-PGE(1) (K(i)=3.07+/-0.29 nM). Interestingly, synthetic
      DP receptor-specific agonists such as BW245C (K(i)=64.7+/-1.0 nM; n=3) and
      ZK118182 (K(i)=425+/-42 nM; n=4), and the purported EP(3) receptor-specific
      ligand enprostil (K(i)=43.1+/-4.4 nM), also displayed high affinity for the EP(4)
      receptor. Two known EP(4) receptor antagonists were weak inhibitors of [(3)H]
      PGE(2) binding akin to their known functional potencies, thus: AH23848
      (K(i)=2690+/-232 nM); AH22921 (K(i)=31,800+/-4090 nM). These studies have
      provided a detailed pharmacological characterization of the recombinant human
      EP(4) receptor expressed in HEK-293 cells.

PMID- 10952684
TI  - The 5HT(1B) receptor agonist, CP-93129, inhibits [(3)H]-GABA release from rat
      globus pallidus slices and reverses akinesia following intrapallidal injection in
      the reserpine-treated rat.
AB  - This study examined whether activation of 5HT(1B) receptors in the rodent globus
      pallidus (GP) could reduce GABA release in vitro and reverse reserpine-induced
      akinesia in vivo. Microdissected slices of GP from male Sprague Dawley rats (300
      350 g) were preloaded with [(3)H]-GABA. During subsequent superfusion, 4 min
      fractions were collected for analysis of release. The effects of the 5HT(1B)
      receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3, 2-b]pyrid-5-one (CP
      93129), on 25 mM KCl-evoked release were examined using a standard dual
      stimulation paradigm. Male Sprague Dawley rats (270 - 290 g), stereotaxically
      cannulated above the GP, were rendered akinetic by injection of reserpine (5 mg
      kg(-1) s.c.). Eighteen hours later, the rotational behaviour induced by
      unilateral injection of CP-93129 was examined. CP-93129 (0.6-16.2 microM)
      produced a concentration-dependent inhibition of 25 mM KCl-evoked [(3)H]-GABA
      release reaching a maximum inhibition of 52.5+/-4.5%. The effect of a submaximal
      concentration of CP-93129 (5.4 microM) was fully inhibited by the 5HT(1B)
      receptor antagonist, isamoltane (10 microM). Following intrapallidal injection,
      CP-93129 (30-330 nmol in 0.5 microl) produced a dose-dependent increase in net
      contraversive rotations reaching a maximum of 197+/-32 rotations in 240 min at
      330 nmol. Pre-treatment with isamoltane (10 nmol in 1 microl) inhibited the
      effects of a submaximal dose of CP-93129 (220 nmol) by 84+/-6%. These data
      suggest that at least some 5HT(1B) receptor function as heteroreceptors in the
      GP, reducing the release of GABA. Moreover, CP-93129-mediated activation of these
      receptors in the GP provides relief of akinesia in the reserpine-treated rat
      model of PD.

PMID- 10952682
TI  - The progestin levonorgestrel induces endothelium-independent relaxation of rabbit
      jugular vein via inhibition of calcium entry and protein kinase C: role of cyclic
      AMP.
AB  - The progestin and oestrogen component of oral contraceptives have been involved
      in the development of venous thromboembolic events in women. In the present study
      we determined the vasoactive effects of sex steroids used in oral contraceptives
      in isolated preconstricted rabbit jugular veins in the presence of diclofenac and
      examined the underlying mechanisms. The natural hormone progesterone, the
      synthetic progestins levonorgestrel, 3-keto-desogestrel, gestodene and
      chlormadinone acetate, and the synthetic estrogen 17 alpha-ethinyloestradiol
      induced concentration-dependent relaxations of endothelium-intact veins
      constricted with U46619. Levonorgestrel also inhibited constrictions evoked by
      either a high potassium (K(+)) solution or phorbol myristate acetate (PMA) in the
      absence and presence of extracellular calcium (Ca(2+)). In addition,
      levonorgestrel depressed contractions evoked by Ca(2+) and reduced (45)Ca(2+)
      influx in depolarized veins. Relaxations to levonorgestrel in U46619-constricted
      veins were neither affected by the presence of the endothelium nor by the
      inhibitor of soluble guanylyl cyclase, NS2028, but were significantly improved
      either by the selective cyclic AMP phosphodiesterase inhibitor rolipram or in the
      absence of diclofenac, and decreased by the protein kinase A inhibitor, Rp-8-CPT
      cAMPS. Rolipram also potentiated relaxations to levonorgestrel in PMA-constricted
      veins in the presence, but not in the absence of extracellular Ca(2+).
      Levonorgestrel increased levels of cyclic AMP and inhibited PMA-induced
      activation of protein kinase C in veins. These findings indicate that
      levonorgestrel caused endothelium-independent relaxations of jugular veins via
      inhibition of Ca(2+) entry and of protein kinase C activation. In addition, the
      cyclic AMP effector pathway contributes to the levonorgestrel-induced relaxation
      possibly by depressing Ca(2+) entry.

PMID- 10952686
TI  - Insulin-like effect of pinitol.
AB  - D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional
      antidiabetic plant Bougainvillea spectabilis, is claimed to exert insulin-like
      effects. This study investigates the effect of D-pinitol on glucose homeostasis
      in animal models of diabetes, and on glucose transport by cultured muscle cells.
      Plasma glucose concentrations were measured in normal, obese-diabetic (ob/ob) and
      streptozotocin (STZ)-diabetic mice after oral (p.o.) and intraperitoneal (i.p.)
      administration of D-pinitol. Glucose transport was measured in L6 rat muscle
      cells by 2-deoxyglucose (2DG) uptake. In STZ-diabetic mice, 100 mg kg(-1) p.o. D
      pinitol acutely decreased the hyperglycaemia (by 22% at 6 h). A similar decrease
      in plasma glucose (by 21%) was observed after 100 mg kg(-1) i.p. D-pinitol.
      Insulin concentrations and the rate of insulin-induced (1 unit kg(-1) actrapid
      i.p.) glucose disappearance were not altered by 100 mg kg(-1) p.o. D-pinitol.
      Chronic administration of D-pinitol (100 mg kg(-1) i.p. twice daily for 11 days)
      to STZ-diabetic mice maintained a reduction in plasma glucose concentrations from
      about 14 to 10 mmol l(-1). In normal non-diabetic and severely insulin resistant
      ob/ob mice, 100 mg kg(-1) p.o. D-pinitol did not significantly affect plasma
      glucose or insulin during acute studies. Incubation of L6 muscle cells with D
      pinitol (10(-3) M) increased basal 2DG uptake by 41% after 10 min and by 34%
      after 4 h. The effect of D-pinitol was inhibited by the phosphatidylinositol 3
      kinase inhibitor LY294002. D-pinitol did not increase insulin-stimulated 2DG
      uptake by L6 cells. The data support the view that D-pinitol can exert an insulin
      like effect to improve glycaemic control in hypoinsulinaemic STZ-diabetic mice. D
      pinitol may act via a post-receptor pathway of insulin action affecting glucose
      uptake.

PMID- 10952685
TI  - Replacement of the carboxylic acid group of prostaglandin f(2alpha) with a
      hydroxyl or methoxy substituent provides biologically unique compounds.
AB  - Replacement of the carboxylic acid group of PGF(2alpha) with the non-acidic
      substituents hydroxyl (-OH) or methoxy (-OCH(3)) resulted in an unexpected
      activity profile. Although PGF(2alpha) 1-OH and PGF(2alpha) 1-OCH(3) exhibited
      potent contractile effects similar to 17-phenyl PGF(2alpha) in the cat lung
      parenchymal preparation, they were approximately 1000 times less potent than 17
      phenyl PGF(2alpha) in stimulating recombinant feline and human FP receptors. In
      human dermal fibroblasts and Swiss 3T3 cells PGF(2alpha) 1-OH and PGF(2alpha) 1
      OCH(3) produced no Ca(2+) signal until a 1 microM concentration was exceeded.
      Pretreatment of Swiss 3T3 cells with either 1 microM PGF(2alpha) 1-OH or
      PGF(2alpha) 1-OCH(3) did not attenuate Ca(2+) signal responses produced by
      PGF(2alpha) or fluprostenol. In the rat uterus, PGF(2alpha) 1-OH was about two
      orders of magnitude less potent than 17-phenyl PGF(2alpha) whereas PGF(2alpha) 1
      OCH(3) produced only a minimal effect. Radioligand binding studies on cat lung
      parenchymal plasma membrane preparations suggested that the cat lung parenchyma
      does not contain a homogeneous population of receptors that equally respond to
      PGF(2alpha)1-OH, PGF(2alpha)1-OCH(3), and classical FP receptor agonists. Studies
      on smooth muscle preparations and cells containing DP, EP(1), EP(2), EP(3),
      EP(4), IP, and TP receptors indicated that the activity of PGF(2alpha) 1-OH and
      PGF(2alpha) 1-OCH(3) could not be ascribed to interaction with these receptors.
      The potent effects of PGF(2alpha) 1-OH and PGF(2alpha) 1-OCH(3) on the cat lung
      parenchyma are difficult to describe in terms of interaction with the FP or any
      other known prostanoid receptor.

PMID- 10952687
TI  - Intestinal anti-inflammatory activity of UR-12746, a novel 5-ASA conjugate, on
      acute and chronic experimental colitis in the rat.
AB  - The present study was undertaken to investigate the intestinal anti-inflammatory
      effects of UR-12746 on the acute and chronic stages of a trinitrobenzene
      sulphonic acid (TNBS) experimental model of inflammatory bowel disease (IBD) in
      the rat. UR-12746 is a novel, locally-acting compound which combines, through an
      azo bond, 5-aminosalicylic (5-ASA) and UR-12715, a potent platelet activating
      factor (PAF)-antagonist. UR-12746 oral pretreatment of colitic rats (50 and 100
      mg kg(-1)) reduced acute colonic damage when evaluated 2 days after colonic
      insult. Postreatment for 4 weeks with UR-12746 (50 and 100 mg kg(-1)) resulted in
      a faster recovery of the damaged colonic mucosa, which was macroscopically
      significant from the third week. The intestinal anti-inflammatory effect of UR
      12746 was associated with a decrease in leukocyte infiltration in the colonic
      mucosa, which was evidenced both biochemically, by a reduction in myeloperoxidase
      activity, and histologically, by a lower leukocyte count after morphometric
      analysis. This effect was higher than that seen with sulphasalazine, when assayed
      at the same doses and in the same experimental conditions. Several mechanisms can
      be involved in the beneficial effects showed by UR-12746: inhibition of
      leukotriene B(4) synthesis in the inflamed colon, improvement of the altered
      colonic oxidative status, and reduction of colonic interleukin-1beta production.
      The results suggest that the intestinal anti-inflammatory activity of UR-12746
      can be attributed to the additive effects exerted by 5-ASA and UR-12715, the PAF
      antagonist compound, that are released in the colonic lumen after reduction of
      the azo bond by the intestinal bacteria.

PMID- 10952688
TI  - Functional, biochemical and molecular biological evidence for a possible beta(3)
      adrenoceptor in human near-term myometrium.
AB  - The possible existence of a beta(3)-adrenoceptor (beta(3)-AR) in human near-term
      myometrium was investigated by in vitro functional and biochemical studies and
      analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective
      agonists and a partial agonist, respectively, of the beta(3)-AR), salbutamol and
      terbutaline (beta(2)-AR agonists) each produced a concentration-dependent
      relaxation of the myometrial spontaneous contractions. There were no differences
      in pD(2) values for the relaxing potencies of terbutaline, salbutamol, CGP 12177
      and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR
      59104A>terbutaline approximately salbutamol approximately CGP 12177 (E(max)=52+/
      7%, 42+/-12% and approximately 30% respectively). Propranolol, a beta(1)- and
      beta(2)-AR antagonist, and ICI 118551, a beta(2)-AR antagonist (both at 0.1
      microM), did not affect the SR 59119A-induced relaxation whereas SR 59230A, a
      selective beta(3)-AR antagonist (1 microM), significantly reduced the maximal
      relaxing effect of SR 59119A. SR 59119A and salbutamol induced a significant
      increase in cyclic AMP levels that was antagonized by SR 59230A but not by
      propranolol for SR 59119A, and by propranolol but not by SR 59230A for
      salbutamol. The beta(3)-AR mRNA was positively expressed in myometrium
      preparations in a reverse transcription polymerase chain assay. The results
      presented provide the first evidence for the existence of the beta(3)-AR subtype
      in human near-term myometrium and suggest that the effects of SR 59119A might be
      mediated through an increase in cyclic AMP level.

PMID- 10952689
TI  - Inhibition of HERG potassium channels by the antimalarial agent halofantrine.
AB  - Halofantrine is a widely used antimalarial agent which has been associated with
      prolongation of the 'QT interval' of the electrocardiogram (ECG), torsades de
      pointes and sudden death. Whilst QT prolongation is consistent with halofantrine
      induced increases in cardiac ventricular action potential duration, the cellular
      mechanism for these observations has not been previously reported. The delayed
      rectifier potassium channel, I(Kr), is a primary site of action of drugs causing
      QT prolongation and is encoded by the human-ether-a-go-go-related gene (HERG). We
      examined the effects of halofantrine on HERG potassium channels stably expressed
      in Chinese hamster ovary (CHO-K1) cells. Halofantrine blocked HERG tail currents
      elicited on repolarization to -60 mV from +30 mV with an IC(50) of 196.9 nM. The
      therapeutic plasma concentration range for halofantrine is 1.67-2.98 microM.
      Channel inhibition by halofantrine exhibited time-, voltage- and use-dependence.
      Halofantrine did not alter the time course of channel activation or deactivation,
      but inactivation was accelerated and there was a 20 mV hyperpolarizing shift in
      the mid-activation potential of steady-state inactivation. Block was enhanced by
      pulses that render channels inactivated, and channel blockade increased with
      increasing duration of depolarizing pulses. We conclude that HERG channel
      inhibition by halofantrine is the likely underlying cellular mechanism for QT
      prolongation. Our data suggest preferential binding of halofantrine to the open
      and inactivated channel states.

PMID- 10952690
TI  - Pharmacological characterization of volume-sensitive, taurine permeable anion
      channels in rat supraoptic glial cells.
AB  - To characterize the volume-sensitive, osmolyte permeable anion channels
      responsible for the osmodependent release of taurine from supraoptic nucleus
      (SON) astrocytes, we investigated the pharmacological properties of the [(3)H]
      taurine efflux from acutely isolated SON. Taurine release induced by hypotonic
      stimulus (250 mosmol l(-1)) was not antagonized by the taurine transporter
      blocker guanidinoethyl sulphonate, confirming the lack of implication of the
      transporter. The osmodependent release of taurine was blocked by a variety of Cl(
      ) channel inhibitors with the order of potency: NPPB>niflumic acid>DPC>DIDS>ATP.
      On the other hand, release of taurine was only weakly affected by other compounds
      (dideoxyforskolin, 4-bromophenacyl bromide, mibefradil) known to block volume
      activated anion channels in other cell preparations, and was completely
      insensitive to tamoxifen, a broad inhibitor of these channels. Although the
      molecular identity of volume-sensitive anion channels is not firmly established,
      a few genes have been postulated as potential candidates to encode such channels.
      We checked the expression in the SON of three of them, ClC(3), phospholemman and
      VDAC(1), and found that the transcripts of these genes are found in SON neurons,
      but not in astrocytes. Similar observation was previously reported for ClC(2). In
      conclusion, the osmodependent taurine permeable channels of SON astrocytes
      display a particular pharmacological profile, suggesting the expression of a
      particular type or subtype of volume-sensitive anion channel, which is likely to
      be formed by yet unidentified proteins.

PMID- 10952691
TI  - Comparison of the pharmacological properties of EDHF-mediated vasorelaxation in
      guinea-pig cerebral and mesenteric resistance vessels.
AB  - In the presence of L-NNA (100 microM), indomethacin (10 microM) and ODQ (10
      microM), acetylcholine induced a concentration-dependent vasorelaxation of guinea
      pig mesenteric and middle cerebral arteries precontracted with cirazoline or
      histamine, but not with high K(+), indicating the contribution of an endothelium
      derived hyperpolarizing factor (EDHF). In cerebral arteries, charybdotoxin (ChTX;
      0.1 microM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive
      relaxation; iberiotoxin (IbTX, 0.1 microM), 4-aminopyridine (4-AP, 1 mM), or
      barium (30 microM) significantly reduced the response; in the mesenteric artery,
      ChTX and IbTX also reduced this relaxation. Glibenclamide (10 microM) had no
      affect in either the mesenteric or cerebral artery. Neither clotrimazole (1
      microM) nor 7-ethoxyresorufin (3 microM) affected EDHF-mediated relaxation in the
      mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the
      cerebral artery. AM404 (30 microM), a selective anandamide transport inhibitor,
      did not affect the vasorelaxation response to acetylcholine in the cerebral
      artery, but in the mesenteric artery potentiated the vasorelaxation response to
      acetylcholine in an IbTX, and apamin-sensitive, but SR 141816A-insensitive
      manner. Ouabain (100 microM) almost abolished EDHF-mediated relaxation in the
      mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the
      addition of K(+) (5 - 20 mM) to precontracted guinea-pig cerebral or mesenteric
      artery induced further vasoconstriction. These data suggest that in the guinea
      pig mesenteric and cerebral arteries different EDHFs mediate acetylcholine
      induced relaxation, however, EDHF is unlikely to be mediated by K(+).

PMID- 10952692
TI  - Selective monoamine oxidase subtype inhibition and striatal extracellular
      dopamine in the guinea-pig.
AB  - Striatal microdialysate levels of dopamine (DA) in conscious guinea-pigs were
      measured following acute (1 day) and chronic (21 days) treatment with deprenyl (2
      and 0.25 mg kg(-1) s.c., respectively) or clorgyline (4 and 1 mg kg(-1) s.c.,
      respectively), as well as by combination treatment using the same doses of the
      two inhibitors. These treatments caused selective inhibition of monoamine oxidase
      type B (MAO-B) or monoamine oxidase type A (MAO-A) respectively. Neither acute
      nor chronic treatments with deprenyl or clorgyline increased basal or KCl-induced
      DA levels. Acute and chronic clorgyline treatments were accompanied by
      significant reductions in striatal microdialysate 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA). On the other hand, both acute and chronic
      deprenyl treatments were accompanied by significant increases in microdialysate
      HVA with no effect on DOPAC levels. Acute or chronic combined treatment with
      clorgyline and deprenyl increased tissue but not microdialysate DA levels. The
      combination treatment given chronically also reduced KCl-induced DA release but
      enhanced amphetamine-induced DA release. Microdialysate DA levels increased to a
      smaller extent in guinea-pig than in rat following local striatal infusion of GBR
      12909 (100 microM). The difference between guinea-pigs and rats in the response
      to GBR-12909, could be the result of a lower dopaminergic innervation and/or
      density of DA transporter. This difference may explain why striatal
      microdialysate DA levels increased following chronic deprenyl treatment in the
      rat but not in the guinea-pig.

PMID- 10952693
TI  - Comparison of zofenopril and lisinopril to study the role of the sulfhydryl-group
      in improvement of endothelial dysfunction with ACE-inhibitors in experimental
      heart failure.
AB  - We evaluated the role of SH-groups in improvement of endothelial dysfunction with
      ACE-inhibitors in experimental heart failure. To this end, we compared the
      vasoprotective effect of chronic treatment with zofenopril (plus SH-group) versus
      lisinopril (no SH-group), or N-acetylcysteine (only SH-group) in myocardial
      infarcted (MI) heart failure rats. After 11 weeks of treatment, aortas were
      obtained and studied as ring preparations for endothelium-dependent and 
      independent dilatation in continuous presence of indomethacin to avoid
      interference of vasoactive prostanoids, and the selective presence of the NOS
      inhibitor L-NMMA to determine NO-contribution. Total dilatation after receptor
      dependent stimulation with acetylcholine (ACh) was attenuated (-49%, P<0.05) in
      untreated MI (n=11), compared to control rats with no-MI (n=8). This was in part
      due to impaired NO-contribution in MI (-50%, P<0.05 versus no-MI). At the same
      time the capacity for generation of biologically active NO after receptor
      independent stimulation with A23187 remained intact. Chronic treatment with n
      acetylcysteine (n=8) selectively restored NO-contribution in total dilatation to
      ACh. In contrast, both ACE-inhibitors fully normalized total dilatation to ACh,
      including the part mediated by NO (no significant differences between zofenopril
      (n=10) and lisinopril (n=8)). Zofenopril, but not lisinopril, additionally
      potentiated the effect of endogenous NO after A23187-induced release from the
      endothelium (+100%) as well as that of exogenous NO provided by nitroglycerin
      (+22%) and sodium nitrite (+36%) (for all P<0.05 versus no-MI). We conclude that
      ACE-inhibition with a SH-group has a potential advantage in improvement of
      endothelial dysfunction through increased activity of NO after release from the
      endothelium into the vessel wall. Furthermore, this is the first study
      demonstrating the selective normalizing effect of N-actylcysteine on NO
      contribution to ACh-induced dilatation in experimental heart failure.

PMID- 10952694
TI  - No involvement of nicotinic receptors in the facilitation of acetylcholine
      outflow in mouse cortex in the presence of neostigmine and atropine.
AB  - The role of nicotinic and muscarinic receptors in the modulation of acetylcholine
      release was studied using field stimulated mouse cortex slices incubated with
      [(3)H]-choline. Both acetylcholine (100 microM) and the cholinesterase inhibitor
      neostigmine (100 microM) inhibited the stimulation-induced (S-I) outflow of
      radioactivity but in the presence of atropine (0.3 microM) an enhancement was
      seen, which may be indicative of facilitatory nicotinic receptors. Mecamylamine
      (100 microM) was unable to antagonize the enhancement seen in the presence of
      acetylcholine and atropine. The nicotinic agonist dimethylphenylpiperazinium (30
      microM) did not facilitate S-I outflow of radioactivity. A range of nicotinic
      blockers had no effect on the enhancement seen in the presence of neostigmine and
      atropine, nor did indomethacin, the 5HT(3) antagonist MDL 7222 nor the NMDA
      antagonist MK-801. The inability to block this effect suggests that nicotinic
      receptors are not involved. We postulate, at least for neostigmine, that the
      facilitation is an artefact because of the use of [(3)H]-choline as a radiotracer
      whereby the efflux of radioactivity is enhanced because the radiolabelled
      acetylcholine is not metabolized to choline and therefore flows out of the tissue
      more readily.

PMID- 10952695
TI  - Barnidipine block of L-type Ca(2+) channel currents in rat ventricular
      cardiomyocytes.
AB  - The effects of barnidipine and nifedipine on L-type Ca(2+) current (I(Ca(L)))
      were investigated in ventricular cardiomyocytes from rats. Both barnidipine and
      nifedipine reduced I(Ca(L)) in a concentration and voltage dependent manner; the
      EC(50) were 80 and 130 nM at a holding potential of -80 mV, respectively, and 18
      and 6 nM at -40 mV, respectively. Both drugs induced a leftward shift of the
      steady-state inactivation curve of I(Ca(L)). Using a twin pulse protocol, the
      relationships between the amount of block of I(Ca(L)) by either drug, seen during
      the second pulse, and the length of the first pulse were described by
      monoexponential functions reflecting onset of block, dependent on drug
      concentration. The onset of block by barnidipine was three times faster than that
      by nifedipine. With both drugs, recovery of I(Ca(L)) was 50 times slower than
      under control conditions and described by monoexponential functions reflecting
      offset of block (independent of drug concentration). The offset of block with
      barnidipine was three times slower than that with nifedipine. The time constants
      of block and unblock of I(Ca(L)) by both drugs were used to calculate binding and
      unbinding and to predict their effects at two frequencies. It is suggested that
      barnidipine exhibits a higher affinity to the inactivated Ca(2+) channel state as
      compared to nifedipine.

PMID- 10952697
TI  - Incubators

PMID- 10952696
TI  - Management of preterm labour.

PMID- 10952698
TI  - Randomised trial of iodine intake and thyroid status in preterm infants.
AB  - BACKGROUND: Low levels of circulating thyroid hormones have been associated with
      poorer general and neurodevelopmental outcome in preterm babies and it has been
      speculated that the association is causal. Low levels of circulating thyroid
      hormone have been reported after inadequate intake of iodine in preterm infants
      being fed milk formula. AIM: To investigate whether increased iodine intake from
      supplemented preterm formula would improve thyroid hormone levels in preterm
      babies (this study) and hence improve neurodevelopmental status (planned
      subsequent study). METHOD: A total of 121 preterm infants were entered into a
      randomised controlled trial of standard (68 microg/l) versus increased (272
      microg/l) iodine in preterm formula. RESULTS: The two groups were comparable at
      recruitment. No evidence of an effect of the intervention on thyroid hormone
      levels was seen up to 41 weeks after conception. CONCLUSION: Calls for increased
      iodine content of preterm infant formulas are not justified by this study.

PMID- 10952699
TI  - Randomised trial of fluid restriction in ventilated very low birthweight infants.
AB  - BACKGROUND: Fluid restriction has been reported to improve survival of infants
      without chronic lung disease (CLD), but it remains unknown whether it reduces CLD
      in a population at high risk of CLD routinely exposed to antenatal steroids and
      postnatal surfactant without increasing other adverse outcomes. AIM: To
      investigate the impact of fluid restriction on the outcome of ventilated, very
      low birthweight infants. STUDY DESIGN: A randomised trial of two fluid input
      levels in the perinatal period was performed. A total of 168 ventilated infants
      (median gestational age 27 weeks (range 23-33)) were randomly assigned to receive
      standard volumes of fluid (60 ml/kg on day 1 progressing to 150 ml/kg on day 7)
      or be restricted to about 80% of standard input. RESULTS: Similar proportions of
      infants on the two regimens had CLD beyond 28 days (56% v 51%) and 36 weeks post
      conceptional age (26% v 25%), survived without oxygen dependency at 28 days (31%
      v 27%) and 36 weeks post conceptional age (58% v 52%), and developed acute renal
      failure. There were no statistically significant differences between other
      outcomes, except that fewer of the restricted group (19% v 43%) required
      postnatal steroids (p < 0.01). In the trial population overall, duration of
      oxygen dependency related significantly to the colloid (p < 0.01), but not
      crystalloid, input level; after adjustment for specified covariates, the hazard
      ratio was 1.07 (95% confidence interval 1.02 to 1.13). CONCLUSIONS: In
      ventilated, very low birthweight infants, fluid restriction in the perinatal
      period neither reduces CLD nor increases other adverse outcomes. Colloid
      infusion, however, is associated with increased duration of oxygen dependency.

PMID- 10952700
TI  - A comparison of indices of respiratory failure in ventilated preterm infants.
AB  - AIM: To compare indices of respiratory failure in terms of their ability to
      predict adverse respiratory outcomes in preterm infants. The indices evaluated
      were: (a) the alveolar-arterial oxygen tension difference (A-aDO(2)); (b) the
      ratio of arterial to alveolar oxygen tension (a/A ratio); (c) the oxygenation
      index (OI); (d) the fractional inspired oxygen concentration (FIO(2)). METHODS:
      Details of respiratory support and arterial blood gas data in the first 24 hours
      of life were collected in ventilated infants below 34 weeks gestation. The worst
      single value of a particular index in the first 24 hours was chosen to quantify
      the severity of respiratory failure in each infant. Receiver operating
      characteristic curves were constructed and areas under the curve (AUC) calculated
      to compare the performance of the indices in predicting death from respiratory
      failure and/or the development of chronic lung disease (CLD). RESULTS: A total of
      155 preterm infants were studied, of whom 35 (23%) died primarily from
      respiratory failure and 53 of the 120 survivors (44%) developed CLD. The overall
      performance of the four indices in predicting death from respiratory failure
      ranged from 0. 77 (AUC for maximum FIO(2)) to 0.88 (AUC for minimum a/A ratio).
      The corresponding AUCs for gestational age and birth weight were 0.75 and 0.76
      respectively. In contrast, demographic variables tended to perform better than
      indices of respiratory failure in predicting CLD/death. CONCLUSIONS: There was no
      evidence of a significant difference between the performance of the a/A ratio, A
      aDO(2), and OI in predicting adverse respiratory outcomes. Use of the OI is
      recommended because of its ease of calculation.

PMID- 10952701
TI  - Cardiovascular effects of an intravenous bolus of morphine in the ventilated
      preterm infant.
AB  - AIM: To examine the cardiovascular effects of an intravenous bolus of morphine,
      100 microg/kg, in 17 ventilated preterm infants. METHODS: Heart rate and blood
      pressure were monitored. Right ventricular output, superior vena caval flow, and
      the width of the ductus arteriosus were measured by Doppler echocardiography 10
      and 60 minutes after the morphine injection, and the values compared with
      baseline values by the paired t test. RESULTS: There was a small but significant
      fall in heart rate (2.1% at 10 minutes, 4.3% at 60 minutes) consistent with a
      sedative effect. There was no effect on systolic, diastolic, or mean blood
      pressure. There was no significant effect on systemic blood flow as measured by
      either right ventricular output or superior vena caval flow. Ductal width was
      significantly reduced by a mean of 16% at 60 minutes, suggesting that normal duct
      closure was not inhibited. CONCLUSION: No cardiovascular effects of an
      intravenous bolus of morphine could be detected.

PMID- 10952702
TI  - Maturation of primary and permanent teeth in preterm infants.
AB  - AIMS: To elucidate the development of primary and permanent teeth and to
      interpret the effect of different calcium, phosphorus, and vitamin D
      supplementation in the neonatal period on dental maturation in preterm children.
      METHODS: Preterm infants were randomised to four groups to receive a vitamin D
      dose of 500 or 1000 IU/day and calcium and phosphorus supplemented or
      unsupplemented breast milk. The maturity of the primary and permanent teeth was
      recorded in 30 preterm children. Sixty children aged 2 years and 60 children aged
      9-11 years served as controls. Bone mineral content/density was assessed in the
      preterm infants. RESULTS: The median (range) corrected teething age was 7 (2-16)
      months in preterm infants and 6 (2-12) months in controls (p = 0.43). The median
      (range) number of erupted teeth at 2 years of age was 16 (11-19) in preterm
      infants and 16 (12-20) in controls (p = 0.16). Maturation of the permanent teeth
      in the preterm infants was not delayed compared with the controls (mean Demirjian
      SDS 0.16 v 0.49, p = 0.14). Early dietary intake of either mineral or vitamin D
      did not affect maturation of the primary dentition in preterm children. Children
      receiving the higher vitamin D dose in the neonatal period had more mature
      permanent dentition than those receiving the lower dose, but mineral intake did
      not affect maturation of the permanent teeth. Dental maturation did not correlate
      with bone mineral status. CONCLUSIONS: This is the first longitudinal study to
      follow primary and permanent tooth maturation in the same preterm children.
      Premature birth has no appreciable late sequelae in tooth maturation.

PMID- 10952703
TI  - Effects of prematurity, intrauterine growth status, and early dexamethasone
      treatment on postnatal bone mineralisation.
AB  - AIM: To examine the hypothesis that, apart from prematurity, intrauterine growth
      status (expressed as gestational age specific birth weight standard deviation
      scores), neonatal factors, and duration of dexamethasone treatment influence bone
      mineralisation in early infancy. METHODS: In this prospective study, groups
      consisted of 15 preterm small for gestational age infants (SGA group) and 43
      preterm appropriate for gestational age infants (AGA group). A reference group
      contained 17 term infants. Body size is known to affect bone mineral content
      (BMC), therefore postnatal bone mineralisation was measured when the study
      infants and controls had attained a similar body size. Bone mineral density (BMD)
      and BMC were determined by dual energy x ray absorptiometer of the lumbar spine
      (L2-L4). RESULTS: Both preterm groups had significantly lower BMC and BMD than
      the weight matched term reference group, but no difference was found in BMC and
      BMD between preterm SGA and AGA infants. In stepwise regression analysis, bone
      area, duration of dexamethasone treatment, weight at examination, and weight gain
      per week were the most significant factors, explaining 54% of the variance of the
      BMC values. CONCLUSION: In particular, weight at examination, prematurity, and
      possibly dexamethasone treatment, but not intrauterine growth status, affect
      postnatal bone mineralisation.

PMID- 10952704
TI  - Influence of antenatal steroids and sex on maturation of the epidermal barrier in
      the preterm infant.
AB  - BACKGROUND: The epidermal barrier is well developed in term infants but defective
      in the immature infant with important clinical consequences. The development of
      the barrier shares similarities with production of pulmonary surfactant. Studies
      in the rat have shown that barrier maturation is accelerated by antenatal
      steroids, both structurally and functionally. Females have a more mature barrier
      than males at the same gestational age. These factors have not been studied in
      the human. AIM: To examine the influence of antenatal steroids and sex on
      maturation of the epidermal barrier in the preterm infant. SUBJECTS: A total of
      137 infants born before 34 weeks gestation, 80 boys and 57 girls, were studied:
      87 had been exposed to antenatal steroids, and 50 had not; 99 were studied
      prospectively, and 38 had been studied previously. METHOD: Barrier function was
      measured as transepidermal water loss from abdominal skin by evaporimetry.
      Measurements were made within the first 48 hours and corrected to a standard
      relative humidity of 50% (TEWL(50)). RESULTS: The relation between TEWL(50) and
      gestation was exponential with very high levels in the most immature infants. No
      influence of antenatal steroids or sex could be shown. When infants who were
      optimally exposed to antenatal steroids were considered alone, no effect could be
      shown. CONCLUSION: Epidermal maturation in the preterm infant does not appear to
      be influenced by antenatal steroids or sex, suggesting that the mechanism of
      maturation differs from that of the rat.

PMID- 10952705
TI  - Blood glucose levels in a population of healthy, breast fed, term infants of
      appropriate size for gestational age.
AB  - AIM: To determine blood glucose levels in a population of healthy, breast fed,
      term infants of appropriate size for gestational age. METHODS: In a cross
      sectional study, the blood glucose concentration of 223 healthy, breast fed, term
      infants of appropriate size for gestational age was determined at different times
      (between one and 96 hours) after delivery. One sample of blood glucose was taken
      from each infant independent of the feeding time. The glucose concentration was
      correlated with sex, method of delivery, delivery with or without analgesia,
      smoking status of the mother, gestational age, umbilical cord pH, and Apgar
      score. Infants suspected of suffering from intrapartum hypoxia were excluded.
      RESULTS: Blood glucose concentration one hour after delivery was not
      significantly lower than at any other time. Only two infants had low blood
      glucose concentrations one hour after delivery (1.4 and 1.9 mmol/l). There were
      no significant differences in blood glucose concentration between sexes, methods
      of delivery, infants delivered with or without analgesia, and infants born to
      smokers or non-smokers, and there was no further correlation between blood
      glucose concentration and gestational age, umbilical cord pH, or Apgar score.
      DISCUSSION: Very few healthy, breast fed, term infants of appropriate size for
      gestational age have low blood glucose levels, and there is no indication for
      blood glucose monitoring in these infants.

PMID- 10952706
TI  - Energy requirements in Chilean infants.
AB  - AIM: To evaluate the energy requirements of breast fed infants. METHODS: The
      study was conducted in 17 healthy exclusively breast fed infants of normal birth
      weight (mean (SD) 3332 (280) g). Energy expenditure by the doubly labelled water
      method and milk intake by the dose to infant method were measured at 34 (4) days.
      A dose of 0. 2 g/kg deuterium oxide (99.8%) and 2.0 g/kg 10% (18)O labelled water
      was given to the infants, and urine samples were collected for seven consecutive
      days after dosing. RESULTS: The mean (SD) weight of the infants during the period
      of evaluation was 4617 (343) g and weight gain 34.0 (7.5) g/day. Daily milk
      intake was 728 (101) g and its metabolisable energy content 2.71 kJ/g. The energy
      expenditure of the infants was 1205 (312) kJ/day and energy required for growth
      was 607 (130) kJ/day. When combined this produced an energy requirement of 391
      kJ/kg/day for these infants. CONCLUSION: These data agree with those from other
      studies in the United Kingdom and the United States and suggest that adequate
      growth can be achieved with 19.4% less energy than recommended by FAO/WHO/UNU.

PMID- 10952707
TI  - Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to
      valproate.
AB  - AIMS: To define, in a prospective study, the risk of hypoglycaemia-defined as
      blood glucose concentration < 1.8 mmol/l-in term infants exposed in utero to
      valproate and to describe the withdrawal symptoms. METHODS: Twenty epileptic
      women were treated with valproate only during pregnancy and two were treated with
      valproate and carbamazepine. In the first trimester, the daily median dose of
      valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3
      4.8). RESULTS: Thirteen of the 22 infants became hypoglycaemic. One infant had
      eight episodes of hypoglycaemia, one had three episodes, two had two episodes,
      and nine had one episode each. The lowest blood glucose concentration was 1.0
      mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of
      total valproate during the third trimester correlated negatively with blood
      glucose concentration one hour after delivery (p < 0.0003) and with the
      development of hypoglycaemia (p < 0.0001). There was no evidence for
      hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal
      symptoms, which correlated positively with the mean dose of valproate in the
      third trimester and the concentration of the free fraction of valproate in
      maternal plasma at delivery (p < 0.02). CONCLUSIONS: Infants exposed to valproate
      in utero had a significantly elevated risk of hypoglycaemia, and withdrawal
      symptoms were often observed.

PMID- 10952708
TI  - Effects of various arterial infusion solutions on red blood cells in the newborn.
AB  - AIM: To examine in vitro the effects of brief contact with various infusion
      solutions on red blood cells from newborn infants, as occurs in the "waste"
      syringe during routine blood sampling from umbilical artery catheters. The
      mixture of blood and solution in the "waste" syringe is usually reinfused into
      the baby. Reinfused red blood cells may be damaged by the infusion solution. It
      is hypothesised that an isotonic amino acid solution would cause no red blood
      cell agglutination and no more haemolysis than many commonly used solutions.
      METHODS: Blood was obtained from the placentas of 15 normal term babies.
      Haemolysis was estimated by measuring plasma (free) haemoglobin after mock blood
      sampling. Agglutination was measured semiquantitatively by direct observation.
      RESULTS: A 0.25% normal saline solution caused 5.4% haemolysis, significantly
      more than all the other fluids tested. There was less haemolysis with 0. 25%
      normal saline when there was complete mixing of blood and solution within the
      "waste" syringe. Normal saline and isotonic sodium acetate solutions caused <
      0.1% haemolysis, significantly less than all the other fluids tested. The
      isotonic amino acid solution caused 0.8% haemolysis, which is similar to that
      caused by the remaining solutions tested. Agglutination was seen with isotonic
      dextrose and with the two isotonic amino acid solutions containing cysteine.
      CONCLUSIONS: Isotonic amino acid solution (without added cysteine) caused no
      agglutination and the same or less haemolysis than many commonly used solutions
      and may offer advantages in nutrition and fluid balance.

PMID- 10952709
TI  - Developmental changes in erythrocyte Na(+),K(+)-ATPase subunit abundance and
      enzyme activity in neonates.
AB  - AIM: To study the relation between erythrocyte Na(+),K(+)-ATPase subunit isoform
      composition, Na(+),K(+)-ATPase activity, and cation pump function in preterm and
      term neonates. DESIGN: Erythrocyte Na(+),K(+)-ATPase subunit isoform abundance,
      Na(+),K(+)-ATPase activity, and cation pump function were studied in blood
      samples obtained from 56 preterm neonates of 28-32 weeks gestation (group 1), 58
      preterm neonates of 33-36 weeks gestation (group 2), and 122 term neonates (group
      3) during the first two postnatal days. RESULTS: alpha(1) isoform abundance was
      higher and beta(2) isoform abundance was lower in group 1 than in group 3 (p =
      0.0002). alpha(2) and beta(1) isoform abundance did not change with maturation
      and there was no evidence for the presence of the alpha(3) isoform. Gestational
      age was inversely related to Na(+), K(+)-ATPase activity (p = 0.0001) and
      directly related to intracellular Na(+) concentration (p = 0.0025). CONCLUSIONS:
      Expression of the alpha(1) and beta(2) Na(+),K(+)-ATPase subunit isoforms is
      developmentally regulated. The increased abundance of alpha(1) isoforms of
      immature neonates translates to increased ATPase activity. The lower
      intracellular Na(+) concentration of immature neonates suggests that their
      erythrocyte Na(+),K(+)-ATPase cation pump function may also be increased.

PMID- 10952710
TI  - Splanchnic haemodynamic disturbances in perinatal sepsis.
AB  - AIM: To determine the effect of perinatal bacterial infection on the neonatal
      splanchnic circulation. SUBJECTS/SETTING: 76 premature infants with appropriate
      birth weight for gestation admitted for neonatal intensive care. METHODS: Doppler
      ultrasound was used to measure blood flow velocity and pulsatility index in the
      superior mesenteric artery and coeliac axis during the first 24 hours of life.
      Babies were classified according to the results of blood and surface cultures, as
      well as the presence or absence of maternal prolonged membrane rupture. RESULTS:
      Infection status had a significant effect on pulsatility index in both arteries,
      with that in the coeliac axis being reduced from 1.27 to 0.80 in babies with
      infection (p < 0.0001). Coeliac axis blood flow velocity was significantly
      increased in those with infection (from 34.6 to 46.5 cm/s; p < 0.05). CONCLUSION:
      As early as the first day of postnatal life, infected neonates show a pattern of
      splanchnic hyperaemia similar to that found in adult systemic inflammatory
      response syndrome.

PMID- 10952711
TI  - Skin conductance and the stress response from heel stick in preterm infants.
AB  - AIM: To evaluate whether spontaneous skin conductance activity is an objective
      method for measuring the stress response to painful stimuli in premature infants.
      The number and amplitude of the waves and the baseline increase with the activity
      of the sympathetic nervous system. METHODS: In 20 preterm infants of gestational
      age >/= 29 weeks, behavioural state and spontaneous skin conductance activity
      variables were measured for three minutes before, during, and for three minutes
      after heel stick. RESULTS: The number of waves (p < 0.001), the amplitude of the
      waves (p = 0.001), and the level of the behavioural state (p < 0.001) increased
      during heel stick, and then decreased to levels found before the procedure. The
      baseline increased both during (p < 0.001) and after heel stick (p < 0.001),
      compared with levels before. CONCLUSION: Spontaneous skin conductance activity
      reflects the stress response to heel stick in premature infants from at least 29
      weeks of gestational age.

PMID- 10952712
TI  - Normoblasts in large for gestational age infants.
AB  - Thirty one term large for gestational age (LGA) infants of non-diabetic mothers
      were compared with 30 appropriate for gestational age controls. Median absolute
      nucleated red blood cell counts, lymphocyte counts, and packed cell volumes were
      significantly higher in the LGA infants than the controls. It is possible that
      LGA babies of non-diabetic mothers are exposed to relative intrauterine hypoxia.

PMID- 10952714
TI  - Antenatal steroids and the developing brain.
AB  - Randomised clinical trials show that two injections of corticosteroid into the
      mother before preterm delivery reduce respiratory distress syndrome, neonatal
      mortality, and intraventricular haemorrhage. However, repeated courses of
      antenatal steroid are not backed by such evidence of safety and efficacy. Animal
      studies have shown that maternal corticosteroid delays myelination and reduces
      the growth of all fetal brain areas particularly the hippocampus. Corticosteroids
      may reduce or enhance hypoxic-ischaemic injury to the developing brain depending
      on timing and dosage. Clinical trials of maternally administered corticosteroid
      show no evidence of increased disability on follow up but numbers are small.
      Postnatal trials of dexamethasone when brain maturity is still preterm show a
      significant increase in later disability in the dexamethasone treated groups.
      There is evidence from randomised trials, retrospective data, experiments on
      pregnant mice, and the chemical make up of the preparations that betamethasone
      may be safer and more protective of the immature brain than dexamethasone. Single
      course corticosteroid treatment before preterm delivery must still be recommended
      as a life saving and cost effective intervention, but clinicians may wish to
      change from using dexamethasone to betamethasone. In view of the animal and
      postnatal data, clinicians should be cautious with repeated courses of antenatal
      corticosteroids and repetition may be unnecessary for lung maturity.

PMID- 10952713
TI  - Promising stratagems for reducing the burden of neonatal sepsis.

PMID- 10952715
TI  - Dr Carl Crede (1819-1892) and the prevention of ophthalmia neonatorum.

PMID- 10952716
TI  - Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and
      prevents vascular calcification by blocking a process resembling
      osteoclastogenesis.
AB  - High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause
      osteopetrosis with normal tooth eruption and bone elongation and inhibit the
      development and activity of endosteal, but not periosteal, osteoclasts. We
      demonstrate that both intravenous injection of recombinant OPG protein and
      transgenic overexpression of OPG in OPG(-/-) mice effectively rescue the
      osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous
      injection of recombinant OPG over a 4-wk period could not reverse the arterial
      calcification observed in OPG(-/-) mice. In contrast, transgenic OPG delivered
      from mid-gestation through adulthood does prevent the formation of arterial
      calcification in OPG(-/-) mice. Although OPG is normally expressed in arteries,
      OPG ligand (OPGL) and receptor activator of NF-kappaB (RANK) are not detected in
      the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK
      transcripts are detected in the calcified arteries of OPG(-/-) mice. Furthermore,
      RANK transcript expression coincides with the presence of multinuclear osteoclast
      like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may
      play an important role in both pathological and physiological calcification
      processes. Such findings may also explain the observed high clinical incidence of
      vascular calcification in the osteoporotic patient population.

PMID- 10952717
TI  - B lymphocytes regulate dendritic cell (DC) function in vivo: increased
      interleukin 12 production by DCs from B cell-deficient mice results in T helper
      cell type 1 deviation.
AB  - Increasing evidence indicates that dendritic cells (DCs) are the antigen
      presenting cells of the primary immune response. However, several reports suggest
      that B lymphocytes could be required for optimal T cell sensitization. We
      compared the immune responses of wild-type and B cell-deficient (muMT) mice,
      induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells.
      Our data show that lymph node cells from both control and muMT animals were
      primed, but each released distinct cytokine profiles. Lymph node T cells from
      control animals secreted interferon (IFN)-gamma, interleukin (IL)-2, and IL-4,
      whereas those from muMT mice produced IFN-gamma and IL-2 but no IL-4. To test
      whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by
      affecting the function of DCs, we immunized mice by transferring antigen-pulsed
      DCs from wild-type or mutant mice. Injection of control DCs induced the secretion
      of IL-4, IFN-gamma, and IL-2, whereas administration of DCs from muMT animals
      failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed
      that DCs from muMT mice produce higher levels of IL-12p70 than do DCs from wild
      type animals. These data suggest that B lymphocytes regulate the capacity of DCs
      to promote IL-4 secretion, possibly by downregulating their secretion of IL-12,
      thereby favoring the induction of a nonpolarized immune response.

PMID- 10952718
TI  - Differential influence on cytotoxic T lymphocyte epitope presentation by
      controlled expression of either proteasome immunosubunits or PA28.
AB  - The proteasome is the principal provider of major histocompatibility complex
      (MHC) class I-presented peptides. Interferon (IFN)-gamma induces expression of
      three catalytically active proteasome subunits (LMP2, LMP7, and MECL-1) and the
      proteasome-associated activator PA28. These molecules are thought to optimize the
      generation of MHC class I-presented peptides. However, known information on their
      contribution in vivo is very limited. Here, we examined the antigen processing of
      two murine leukemia virus-encoded cytotoxic T lymphocyte (CTL) epitopes in murine
      cell lines equipped with a tetracycline-controlled, IFN-gamma-independent
      expression system. We thus were able to segregate the role of the immunosubunits
      from the role of PA28. The presence of either immunosubunits or PA28 did not
      alter the presentation of a subdominant murine leukemia virus (MuLV)-derived CTL
      epitope. However, the presentation of the immunodominant MuLV-derived epitope was
      markedly enhanced upon induction of each of these two sets of genes. Thus, the
      IFN-gamma-inducible proteasome subunits and PA28 can independently enhance
      antigen presentation of some CTL epitopes. Our data show that tetracycline
      regulated expression of PA28 increases CTL epitope generation without affecting
      the 20S proteasome composition or half-life. The differential effect of these IFN
      gamma-inducible proteins on MHC class I processing may have a decisive influence
      on the quality of the CTL immune response.

PMID- 10952719
TI  - Subsecond induction of alpha4 integrin clustering by immobilized chemokines
      stimulates leukocyte tethering and rolling on endothelial vascular cell adhesion
      molecule 1 under flow conditions.
AB  - Leukocyte recruitment to target tissue is initiated by weak rolling attachments
      to vessel wall ligands followed by firm integrin-dependent arrest triggered by
      endothelial chemokines. We show here that immobilized chemokines can augment not
      only arrest but also earlier integrin-mediated capture (tethering) of lymphocytes
      on inflamed endothelium. Furthermore, when presented in juxtaposition to vascular
      cell adhesion molecule 1 (VCAM-1), the endothelial ligand for the integrin very
      late antigen 4 (VLA-4, alpha4beta1), chemokines rapidly augment reversible
      lymphocyte tethering and rolling adhesions on VCAM-1. Chemokines potentiate VLA-4
      tethering within <0.1 s of contact through Gi protein signaling, the fastest
      inside-out integrin signaling events reported to date. Although VLA-4 affinity is
      not altered upon chemokine signaling, subsecond VLA-4 clustering at the leukocyte
      substrate contact zone results in enhanced leukocyte avidity to VCAM-1.
      Endothelial chemokines thus regulate all steps in adhesive cascades that control
      leukocyte recruitment at specific vascular beds.

PMID- 10952720
TI  - Preformed membrane-associated stores of interleukin (IL)-12 are a previously
      unrecognized source of bioactive IL-12 that is mobilized within minutes of
      contact with an intracellular parasite.
AB  - The prevailing paradigm is that production of the interleukin (IL)-12 p70
      heterodimer, a critical T helper cell type 1 (Th1)-inducing cytokine, depends on
      the induced transcription of the p40 subunit. Concordant with this paradigm, we
      found that dendritic cells (DCs) produced IL-12 p70 only after at least 2-4 h of
      stimulation with lipopolysaccharide plus interferon gamma. However, using several
      complementary experimental approaches, including electron and confocal
      microscopy, we now show that resting murine and human myeloid cells, including
      macrophages/DCs and DC-rich tissues, contain a novel source of bioactive IL-12
      that is preformed and membrane associated. These preformed, membrane-associated
      IL-12 p70 stores are released within minutes after in vitro or in vivo contact
      with Leishmania donovani, an intracellular pathogen. Our findings highlight a
      novel source of bioactive IL-12 that is readily available for the rapid
      initiation of Th1 host responses to pathogens such as Leishmania species.

PMID- 10952721
TI  - Residual type 1 immunity in patients genetically deficient for interleukin 12
      receptor beta1 (IL-12Rbeta1): evidence for an IL-12Rbeta1-independent pathway of
      IL-12 responsiveness in human T cells.
AB  - Genetic lack of interleukin 12 receptor beta1 (IL-12Rbeta1) surface expression
      predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella
      and causes strongly decreased, but not completely abrogated, interferon (IFN)
      gamma production. To study IL-12Rbeta1-independent residual IFN-gamma production,
      we have generated mycobacterium-specific T cell clones (TCCs) from IL-12Rbeta1
      deficient individuals. All TCCs displayed a T helper type 1 phenotype and the
      majority responded to IL-12 by increased IFN-gamma production and proliferative
      responses upon activation. This response to IL-12 could be further augmented by
      exogenous IL-18. IL-12Rbeta2 was found to be normally expressed in the absence of
      IL-12Rbeta1, and could be upregulated by IFN-alpha. Expression of IL-12Rbeta2
      alone, however, was insufficient to induce signal transducer and activator of
      transcription (Stat)4 activation in response to IL-12, whereas IFN-alpha/IFN
      alphaR ligation resulted in Stat4 activation in both control and IL-12Rbeta1
      deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R,
      integrin alpha6, and IL-12Rbeta2 on IL-12Rbeta1-deficient cells, whereas this was
      normal on control cells. IL-12-induced IFN-gamma production in IL-12Rbeta1
      deficient T cells could be inhibited by the p38 mitogen-activated protein kinase
      (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor
      U0126, suggesting involvement of MAP kinases in this alternative, Stat4
      independent, IL-12 signaling pathway.Collectively, these results indicate that IL
      12 acts as a partial agonist in the absence of IL-12Rbeta1. Moreover, the results
      reveal the presence of a novel IL-12Rbeta1/Stat4-independent pathway of IL-12
      responsiveness in activated human T cells involving MAP kinases. This pathway is
      likely to play a role in the residual type 1 immunity in IL-12Rbeta1 deficiency.

PMID- 10952722
TI  - Host-virus interactions during malaria infection in hepatitis B virus transgenic
      mice.
AB  - We have previously shown that hepatitis B virus (HBV) replication is abolished in
      the liver of HBV transgenic mice by inflammatory cytokines induced by HBV
      specific cytotoxic T cells and during unrelated viral infections of the liver. We
      now report that intrahepatic HBV replication is also inhibited in mice infected
      by the malaria species Plasmodium yoelii 17X NL. P. yoelii infection triggers an
      intrahepatic inflammatory response characterized by the influx of natural killer
      cells, macrophages, and T cells. During this process, interferon (IFN)-gamma and
      IFN-alpha/beta suppress HBV gene expression and replication in the liver.
      Collectively, the data suggest that malaria infection might influence the course
      and pathogenesis of HBV infection in coinfected humans.

PMID- 10952723
TI  - Premature expression of T cell receptor (TCR)alphabeta suppresses TCRgammadelta
      gene rearrangement but permits development of gammadelta lineage T cells.
AB  - The T cell receptor (TCR)gammadelta and the pre-TCR promote survival and
      maturation of early thymocyte precursors. Whether these receptors also influence
      gammadelta versus alphabeta lineage determination is less clear. We show here
      that TCRgammadelta gene rearrangements are suppressed in TCRalphabeta transgenic
      mice when the TCRalphabeta is expressed early in T cell development. This
      situation offers the opportunity to examine the outcome of gammadelta versus
      alphabeta T lineage commitment when only the TCRalphabeta is expressed. We find
      that precursor thymocytes expressing TCRalphabeta not only mature in the
      alphabeta pathway as expected, but also as CD4(-)CD8(-) T cells with properties
      of gammadelta lineage cells. In TCRalphabeta transgenic mice, in which the
      transgenic receptor is expressed relatively late, TCRgammadelta rearrangements
      occur normally such that TCRalphabeta(+)CD4(-)CD8(-) cells co-express
      TCRgammadelta. The results support the notion that TCRalphabeta can substitute
      for TCRgammadelta to permit a gammadelta lineage choice and maturation in the
      gammadelta lineage. The findings could fit a model in which lineage commitment is
      determined before or independent of TCR gene rearrangement. However, these
      results could be compatible with a model in which distinct signals bias lineage
      choice and these signaling differences are not absolute or intrinsic to the
      specific TCR structure.

PMID- 10952724
TI  - Homeostasis-stimulated proliferation drives naive T cells to differentiate
      directly into memory T cells.
AB  - The developmental requirements for immunological memory, a central feature of
      adaptive immune responses, is largely obscure. We show that as naive CD8 T cells
      undergo homeostasis-driven proliferation in lymphopenic mice in the absence of
      overt antigenic stimulation, they progressively acquire phenotypic and functional
      characteristics of antigen-induced memory CD8 T cells. Thus, the homeostasis
      induced memory CD8 T cells express typical memory cell markers, lyse target cells
      directly in vitro and in vivo, respond to lower doses of antigen than naive
      cells, and secrete interferon gamma faster upon restimulation. Like antigen
      induced memory T cell differentiation, the homeostasis-driven process requires T
      cell proliferation and, initially, the presence of appropriate restricting major
      histocompatibility complexes, but it differs by occurring without effector cell
      formation and without requiring interleukin 2 or costimulation via CD28. These
      findings define repetitive cell division plus T cell receptor ligation as the
      basic requirements for naive to memory T cell differentiation.

PMID- 10952725
TI  - Naive T cells transiently acquire a memory-like phenotype during homeostasis
      driven proliferation.
AB  - In a depleted lymphoid compartment, naive T cells begin a slow proliferation that
      is independent of cognate antigen yet requires recognition of major
      histocompatibility complex-bound self-peptides. We have followed the phenotypic
      and functional changes that occur when naive CD8(+) T cells undergo this type of
      expansion in a lymphopenic environment. Naive T cells undergoing homeostasis
      driven proliferation convert to a phenotypic and functional state similar to that
      of memory T cells, yet distinct from antigen-activated effector T cells. Naive T
      cells dividing in a lymphopenic host upregulate CD44, CD122 (interleukin 2
      receptor beta) and Ly6C expression, acquire the ability to rapidly secrete
      interferon gamma, and become cytotoxic effectors when stimulated with cognate
      antigen. The conversion of naive T cells to cells masquerading as memory cells in
      response to a homeostatic signal does not represent an irreversible
      differentiation. Once the cellularity of the lymphoid compartment is restored and
      the T cells cease their division, they regain the functional and phenotypic
      characteristics of naive T cells. Thus, homeostasis-driven proliferation provides
      a thymus-independent mechanism for restoration of the naive compartment after a
      loss of T cells.

PMID- 10952726
TI  - High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine
      synthesis in human monocytes.
AB  - Lipopolysaccharide (LPS) is lethal to animals because it activates cytokine
      release, causing septic shock and tissue injury. Early proinflammatory cytokines
      (e.g., tumor necrosis factor [TNF] and interleukin [IL]-1) released within the
      first few hours of endotoxemia stimulate mediator cascades that persist for days
      and can lead to death. High mobility group 1 protein (HMG-1), a ubiquitous DNA
      binding protein, was recently identified as a "late" mediator of endotoxin
      lethality. Anti-HMG-1 antibodies neutralized the delayed increase in serum HMG-1,
      and protected against endotoxin lethality, even when passive immunization was
      delayed until after the early cytokine response. Here we examined whether HMG-1
      might stimulate cytokine synthesis in human peripheral blood mononuclear cell
      cultures. Addition of purified recombinant HMG-1 to human monocyte cultures
      significantly stimulated the release of TNF, IL-1alpha, IL-1beta, IL-1RA, IL-6,
      IL-8, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta; but not IL-10
      or IL-12. HMG-1 concentrations that activated monocytes were within the
      pathological range previously observed in endotoxemic animals, and in serum
      obtained from septic patients. HMG-1 failed to stimulate cytokine release in
      lymphocytes, indicating that cellular stimulation was specific. Cytokine release
      after HMG-1 stimulation was delayed and biphasic compared with LPS stimulation.
      Computer-assisted image analysis demonstrated that peak intensity of HMG-1
      induced cellular TNF staining was comparable to that observed after maximal
      stimulation with LPS. Administration of HMG-1 to Balb/c mice significantly
      increased serum TNF levels in vivo. Together, these results indicate that, like
      other cytokine mediators of endotoxin lethality (e.g., TNF and IL-1),
      extracellular HMG-1 is a regulator of monocyte proinflammatory cytokine
      synthesis.

PMID- 10952727
TI  - Two distinct pathways leading to nuclear apoptosis.
AB  - Apaf-1(-/-) or caspase-3(-/-) cells treated with a variety of apoptosis inducers
      manifest apoptosis-associated alterations including the translocation of
      apoptosis-inducing factor (AIF) from mitochondria to nuclei, large scale DNA
      fragmentation, and initial chromatin condensation (stage I). However, when
      compared with normal control cells, Apaf-1(-/-) or caspase-3(-/-) cells fail to
      exhibit oligonucleosomal chromatin digestion and a more advanced pattern of
      chromatin condensation (stage II). Microinjection of such cells with recombinant
      AIF only causes peripheral chromatin condensation (stage I), whereas
      microinjection with activated caspase-3 or its downstream target caspase
      activated DNAse (CAD) causes a more pronounced type of chromatin condensation
      (stage II). Similarly, when added to purified HeLa nuclei, AIF causes stage I
      chromatin condensation and large-scale DNA fragmentation, whereas CAD induces
      stage II chromatin condensation and oligonucleosomal DNA degradation.
      Furthermore, in a cell-free system, concomitant neutralization of AIF and CAD is
      required to suppress the nuclear DNA loss caused by cytoplasmic extracts from
      apoptotic wild-type cells. In contrast, AIF depletion alone suffices to suppress
      the nuclear DNA loss contained in extracts from apoptotic Apaf-1(-/-) or caspase
      3(-/-) cells. As a result, at least two redundant parallel pathways may lead to
      chromatin processing during apoptosis. One of these pathways involves Apaf-1 and
      caspases, as well as CAD, and leads to oligonucleosomal DNA fragmentation and
      advanced chromatin condensation. The other pathway, which is caspase-independent,
      involves AIF and leads to large-scale DNA fragmentation and peripheral chromatin
      condensation.

PMID- 10952728
TI  - Nuclear factor of activated T cells transcription factor NFATp controls
      superantigen-induced lethal shock.
AB  - Tumor necrosis factor alpha (TNF-alpha) is the key mediator of superantigen
      induced T cell lethal shock. Here, we show that nuclear factor of activated T
      cells transcription factor, NFATp, controls susceptibility to superantigen
      induced lethal shock in mice through its activation of TNF-alpha gene
      transcription. In NFATp-deficient mice, T cell stimulation leads to delayed
      induction and attenuation of TNF-alpha mRNA levels, decreased TNF-alpha serum
      levels, and resistance to superantigen-induced lethal shock. By contrast, after
      lipopolysaccharide (LPS) challenge, serum levels of TNF-alpha and susceptibility
      to shock are unaffected. These results demonstrate that NFATp is an essential
      activator of immediate early TNF-alpha gene expression in T cells and they
      present in vivo evidence of the inducer- and cell type-specific regulation of TNF
      alpha gene expression. Furthermore, they suggest NFATp as a potential selective
      target in the treatment of superantigen-induced lethal shock.

PMID- 10952729
TI  - Macrophage-tropic HIV induces and exploits dendritic cell chemotaxis.
AB  - Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which
      promotes chemotaxis toward the CC chemokines regulated on activation, normal T
      cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)
      1alpha, and MIP-1beta. By contrast, mature DCs downregulate CCR5 but upregulate
      CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis
      toward stromal cell-derived factor (SDF)-1alpha. CCR5 and CXCR4 also function as
      coreceptors for macrophage-tropic (M-tropic) and T cell-tropic (T-tropic) human
      immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of
      iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure
      to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward
      CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation
      of DC-T cell syncytia, thus promoting viral production and destruction of both DC
      and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is
      likely to contribute to immunosuppression in primary infection and AIDS. In
      addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions
      by the abundant DC cell surface protein DC-specific intercellular adhesion
      molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell-specific
      DC-SIGN retains the ability to infect replication-permissive T cells in trans for
      several days. Consequently, recruitment of DC by HIV-1 could combine with the
      ability of DC-SIGN to capture and transmit the virus to T cells, and so
      facilitate dissemination of virus within an infected individual.

PMID- 10952730
TI  - Immune cell activation by bacterial CpG-DNA through myeloid differentiation
      marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6.
AB  - Transition of immature antigen presenting cells (APCs) to the state of
      professional APCs is essential for initiation of cell-mediated immune responses
      to pathogens. Signal transduction via molecules of the Toll-like receptor
      (TLR)/interleukin 1 receptor (IL-1R) pathway is critical for activation of APCs
      either by pathogen-derived pattern ligands like lipopolysaccharides (LPS) or by
      CD40 ligation through T helper cells. The capacity of bacterial DNA (CpG-DNA) to
      induce APCs to differentiate into professional APCs represents an interesting
      discovery. However, the signaling pathways involved are poorly understood. Here
      we show that CpG-DNA activates the TLR/IL-1R signaling pathway via the molecules
      myeloid differentiation marker 88 (MyD88) and tumor necrosis factor receptor
      associated factor 6 (TRAF6), leading to activation of kinases of the IkappaB
      kinase complex and the c-jun NH(2)-terminal kinases. Moreover, cells of TLR2- and
      TLR4-deficient mice are activated by CpG-DNA, whereas cells of MyD88-deficient
      mice do not respond. The data suggest that CpG-DNA initiates signaling via the
      TLR/IL-1R pathway in APCs in a manner similar to LPS and to T helper cell
      mediated CD40 ligation. Activation of the TLR/IL-1R signaling pathway by foreign
      bacterial DNA may be one way to initiate innate defense mechanisms against
      infectious pathogens in vivo.

PMID- 10952732
TI  - Visual attention to the periphery is enhanced in congenitally deaf individuals.
AB  - We compared normally hearing individuals and congenitally deaf individuals as
      they monitored moving stimuli either in the periphery or in the center of the
      visual field. When participants monitored the peripheral visual field, greater
      recruitment (as measured by functional magnetic resonance imaging) of the motion
      selective area MT/MST was observed in deaf than in hearing individuals, whereas
      the two groups were comparable when attending to the central visual field. This
      finding indicates an enhancement of visual attention to peripheral visual space
      in deaf individuals. Structural equation modeling was used to further
      characterize the nature of this plastic change in the deaf. The effective
      connectivity between MT/MST and the posterior parietal cortex was stronger in
      deaf than in hearing individuals during peripheral but not central attention.
      Thus, enhanced peripheral attention to moving stimuli in the deaf may be mediated
      by alterations of the connectivity between MT/MST and the parietal cortex, one of
      the primary centers for spatial representation and attention.

PMID- 10952733
TI  - Activation of presynaptic and postsynaptic ryanodine-sensitive calcium stores is
      required for the induction of long-term depression at GABAergic synapses in the
      neonatal rat hippocampus.
AB  - The role of internal calcium stores in the induction of long-term depression at
      GABAergic synapses was investigated in the neonatal rat hippocampus. Whole-cell
      recordings of CA3 pyramidal neurons were performed on hippocampal slices from
      neonatal (2-4 d old) rats. In control conditions, tetanic stimulation (TS) evoked
      an NMDA-dependent long-term depression of GABA(A) receptor-mediated postsynaptic
      responses (LTD(GABA-A)). LTD(GABA-A) was prevented when the cells were loaded
      with ruthenium red, a blocker of Ca2+-induced Ca2+ release (CICR) stores, whereas
      loading the cells with heparin, a blocker of IP3-induced Ca2+ release stores, had
      no effect. The effects of ryanodine, another compound that interferes with CICR
      stores, were also investigated. Intracellular injection of ryanodine prevented
      the induction of LTD(GABA-A) only when the TS was preceded by depolarizing pulses
      that increase intracellular Ca2+ concentration. When applied in the bath,
      ryanodine prevented the induction of LTD(GABA-A). Altogether, these results
      suggest that ryanodine acts as a Ca2+-dependent blocker of CICR stores and that
      the induction of LTD(GABA-A) required the activation of both presynaptic and
      postsynaptic CICR stores.

PMID- 10952734
TI  - Lessons learnt from the synovial tissue response to anti-rheumatic treatment.

PMID- 10952731
TI  - Homeostatic T cell proliferation: how far can T cells be activated to self
      ligands?

PMID- 10952735
TI  - Advances in our understanding of the bone and joint pathology caused by
      Staphylococcus aureus infection.

PMID- 10952736
TI  - Early inflammatory polyarthritis: results from the norfolk arthritis register
      with a review of the literature. I. Risk factors for the development of
      inflammatory polyarthritis and rheumatoid arthritis.

PMID- 10952737
TI  - Class II MHC antigens in early rheumatoid arthritis in Bath (UK) and Madrid
      (Spain).
AB  - OBJECTIVE: A number of studies have indicated that rheumatoid arthritis (RA) is a
      less severe disease in Mediterranean countries than in Northern Europe. We
      investigated whether differences in the frequency of class II MHC antigens might
      contribute to this variation in disease severity. METHODS: Typing at HLA-DR and 
      DQ loci was carried out at low and high resolutions by polymerase chain reaction
      amplification in patients with early RA of less than 6 months' duration (68
      patients in Madrid and 68 in Bath) and in control subjects (929 in Madrid and 226
      in Bath). Only ethnic Spanish and British individuals were included as patients
      and controls. RESULTS: Shared epitope (SE) alleles represented 19.8 and 28.9% of
      the total number of class II MHC alleles in controls from Madrid and Bath
      respectively (P: = 0.00001), this difference being largely due to increased
      numbers of DRB1*0401 individuals in the British subjects (P: = 0.0000001).
      Analysis of the patients showed the expected increase in SE alleles when compared
      with their respective control groups (Madrid, 31.6 vs 19.8%; Bath, 42.6 vs 28.
      9%). In Bath the SE was mainly encoded by HLA-DR4 alleles (74.1%), while in
      Madrid it was encoded almost equally by DR4 (51.1%) and DR1 (44.7%) alleles. The
      risk of developing RA in carriers of SE alleles was similar in the two cities
      (Bath, odds ratio 1.83, 95% confidence interval 1.23-2.78; Madrid, odds ratio
      1.87, 95% confidence interval 1.25-2.77), and was largely accounted for by HLA
      DRB1*0401 alleles. CONCLUSION: We conclude that rheumatoid patients in Bath
      differ from their Spanish counterparts in class II antigen expression and allele
      frequency. This may be explained partly by genetic differences between the
      control populations in the two centres, and may help to explain the greater
      incidence of more severe rheumatoid disease expression seen in RA patients in the
      UK.

PMID- 10952738
TI  - The role of joint afferents in sensory processing in osteoarthritic knees.
AB  - OBJECTIVE: To test the role of joint receptors for proprioception in patients
      with bilateral knee osteoarthritis (OA) and patients who had undergone unilateral
      total knee arthroplasty (TKA). METHODS: Nine patients were tested bilaterally
      with a conventional movement detection paradigm that evaluated conscious
      detection perception and a newly developed hunting paradigm that measured maximal
      sensory performance (hunting perception). RESULTS: For detection perception,
      patients exhibited a slightly lower threshold on the arthritic side than on their
      TKA side. For hunting perception, the patients showed threshold values that were
      an order of magnitude smaller than for the conventional paradigm in both knees.
      Performance was much better on prosthetic knees than on OA knees. CONCLUSION: The
      joint receptors of OA knees might have an adverse effect on the maximal
      proprioceptive performance, being important for the normal reflexive knee joint
      functions. These deficits may be overcome by joint receptor removal during knee
      replacement.

PMID- 10952739
TI  - Racial origin and its effect on disease expression and HLA-DRB1 types in patients
      with rheumatoid arthritis: a matched cross-sectional study.
AB  - OBJECTIVE: There are a significant number of patients with rheumatoid arthritis
      (RA) of North Indian or Pakistani origin (Asian) now living in the UK. RA has
      been poorly studied in this racial group. The aim of this study was to compare RA
      in this Asian group with RA in the indigenous northern European (European)
      population. It was hypothesized that these two racial groups would have different
      disease expressions and immunogenetics that could be relevant to pathogenesis,
      prognosis and therapy. METHODS: One hundred and seven Asian RA patients, who
      fulfilled the 1987 American College of Rheumatology criteria, were stringently
      matched for age, sex and disease duration with 107 European RA patients, and were
      fully assessed. RESULTS: The Asian RA patients had significantly fewer bony
      erosions [median Larsen score 58.5 (interquartile range 45.5-77.8) vs 68 (52-93)
      for European patients; P: = 0.0066, Mann-Whitney U:-test] and rarely had nodules
      (5.7 vs 20%, P: = 0. 0019, Fisher's exact test). The two groups had the same
      prevalence of rheumatoid factor positivity, number of swollen joints and level of
      inflammation (C-reactive protein). The Asian RA patients had a reduced prevalence
      of the conserved third allelic hypervariable region (3AHVR) (45 vs 82%, P: <
      0.0001, Fisher's exact test), particularly DRB1*0401 (4.5 vs 55%). However, the
      prevalence of the conserved 3AHVR was significantly increased in the Asian RA
      patients compared with Asian controls. By contrast, the Asian patients had more
      tender joints [13.5 (7-22) vs 5.5 (2-11.8); P: < 0.0001 Mann-Whitney U:-test].
      The Health Assessment Questionnaire score was also significantly worse in the
      Asians compared with the Europeans [median 2.0 (1.13-2.63) vs 1.25 (0.5-2.13), P:
      = 0.0001). CONCLUSIONS: The Asian patients had similar levels of inflammation and
      less damage but more pain and disability than the matched European RA patients.
      Of the known prognostic factors for erosions (rheumatoid factor, conserved 3AHVR,
      swollen joints and C-reactive protein), only the conserved 3AHVR was reduced in
      the Asian RA patients, and this was consistent with their less erosive disease.
      These data also indicate the importance of pain as well as erosive damage in
      determining disability in Asian patients and stress the importance of adequate
      pain relief, in addition to disease suppression, when treating Asian RA patients.

PMID- 10952740
TI  - Cyclosporin and tacrolimus: their use in a routine clinical setting for
      scleroderma.
AB  - BACKGROUND: Cyclosporin and tacrolimus are immunomodulatory drugs which act
      predominantly on T cells. Improvements in certain manifestations, particularly
      skin tightness, have been observed in a number of patients with scleroderma
      treated with these drugs. However, to date there have been no reports of their
      use in a routine clinical setting. METHODS: Patients attending clinical
      immunology clinics who had progressive systemic sclerosis and related syndromes
      and who had received cyclosporin and/or tacrolimus were identified. Details of
      their treatment, including drug dosage, duration of and response to treatment,
      side-effects and reasons for withdrawal, were recorded. RESULTS: Sixteen patients
      had been given cyclosporin and 13 of these had been treated for skin tightness.
      Half noticed significant softening of their skin whilst on treatment, and
      resolution was observed in all four of the patients treated for digital
      vasculitis. Side-effects were common and dose-limiting, and contributed to
      withdrawal in 12 out of 13 patients. Eight patients had been treated with
      tacrolimus; two of these had stopped the drug because of progression of their
      disease, one developed diarrhoea, prompting withdrawal, one stopped tacrolimus
      following improvement, and four remained on the drug. Side-effects had occurred
      in three patients. CONCLUSION: Improvements in skin occur in approximately half
      of all cases of scleroderma treated with either cyclosporin or tacrolimus,
      suggesting a beneficial effect. Side-effects, especially hypertension, are common
      with cyclosporin and often necessitate withdrawal. Adverse effects are also
      observed with tacrolimus, but in the small cohort so far treated only one patient
      had stopped the drug for this reason.

PMID- 10952741
TI  - Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: To investigate the distribution of radiolabelled interleukin-1
      receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA) and to
      assess whether this cytokine is suitable for scintigraphic visualization of
      synovitis. METHODS: In patients with active RA, scintigraphy was performed after
      a single i. v. dose of [(123)I]IL-1ra. Clearance and organ distribution of
      radiolabelled IL-1ra were studied. To assess whether radiolabelled IL-1ra targets
      the synovial IL-1 receptors, the scintigraphic images obtained with IL-1ra were
      compared with those obtained by the use of a non-specific control agent. In
      addition, autoradiography was performed in mice with antigen-induced arthritis
      that were injected with either radiolabelled IL-1ra or a size-matched, non
      receptor-binding protein. RESULTS: Radiolabelled IL-1ra allowed clear
      visualization of inflamed joints. Specificity in the detection of synovitis was
      high, whereas a number of painful and swollen joints were not visualized by
      scintigraphy. The procedure was well tolerated and [(123)I]IL-1ra was rapidly
      cleared from the circulation (t(1/2)alpha 11 min, t(1/2)beta 612 min) and
      excreted mainly in the urine. The definition of synovial contours by IL-1ra
      scintigraphy was not better than that observed with a non-specific agent.
      Although radiolabelled IL-1ra retained its affinity for IL-1 receptors, no
      binding to synovium was observed by autoradiography. CONCLUSIONS: Radiolabelled
      IL-1ra allows the visualization of synovitis in patients with RA. However,
      neither the imaging nor the autoradiographic studies indicate that joint
      accumulation of radiolabelled IL-1ra is due to specific IL-1 receptor targeting.
      IL-1ra has proved its therapeutic value in RA, but with the dose schedule in this
      study it does not behave as a specific radiopharmaceutical that is suitable for
      scintigraphic detection of inflammation.

PMID- 10952742
TI  - QT dispersion as a predictor of arrhythmic events in patients with ankylosing
      spondylitis.
AB  - OBJECTIVE: The aim of the study was to evaluate QT dispersion (QTd), an indicator
      of repolarization heterogeneity, and its relation to ventricular arrhythmias in
      patients with ankylosing spondylitis (AS). METHODS: A full history, clinical
      examination, electrocardiograms and 24-h Holter monitoring were performed in 88
      AS patients and 31 volunteers of similar age and sex. Groups were compared based
      on electrocardiographic abnormality, QTd, arrhythmias and heart blocks. RESULTS:
      QTd and corrected QTd (QTcd) were significantly greater in AS patients than
      controls (QTd, 52.8 +/- 15.1 vs 35.5 +/- 8.9 ms, P: < 0.0001; QTcd, 60.3 +/- 16.1
      vs 39.4 +/- 10.7 ms, P: < 0.0001). The magnitudes of these parameters were
      associated with the duration of the disease (QTd, r = 0.56, P: < 0.01; QTcd, r =
      0.60, P: < 0.001). The frequency of ventricular extrasystoles was found to be
      correlated with QTd (r = 0.35, P: < 0.01) and QTcd (r = 0.33, P: < 0. 01).
      CONCLUSION: Involvement of the heart may be seen in AS during the early clinical
      course of the disease. QTd may give clues about the presence of arrhythmias and
      can be used as a new technique for the evaluation of asymptomatic patients.
      Earlier detection of cardiac involvement could alter the prognosis of the
      patients.

PMID- 10952743
TI  - Non-steroidal anti-inflammatory drugs as a possible cause for reversible
      infertility.
AB  - OBJECTIVE: To highlight the possible association between infertility and
      treatment with long-term non-steroidal anti-inflammatory drug (NSAIDs). NSAIDs
      act mainly through the inhibition of cyclooxygenase, the enzyme that catalyses
      the synthesis of prostaglandins, which are essential mediators of ovulation,
      implantation and placentation of the conceptus. METHODS: Case reports of four
      women suffering from severe arthritis, on long-term NSAIDs and undergoing
      extensive investigation and treatment for infertility. RESULTS: During the last 2
      yr, four out of five women with severe arthritis and difficulty conceiving were
      counselled to stop NSAIDs, and they successfully conceived shortly after the
      withdrawal of NSAIDs. CONCLUSION: NSAIDs, used largely for the treatment of
      rheumatological conditions, may be responsible for some cases of infertility.

PMID- 10952744
TI  - A study of the health assessment questionnaire to evaluate functional status in
      polymyalgia rheumatica.
AB  - OBJECTIVE: To evaluate the Health Assessment Questionnaire (HAQ) in the
      assessment of functional status, its responsiveness to change with treatment and
      its correlation with conventional disease activity indices in polymyalgia
      rheumatica (PMR). METHODS: Newly diagnosed patients with PMR, satisfying modified
      Jones and Hazleman criteria, were recruited to the study. The clinical
      assessments, including early morning stiffness (EMS), pain measured on a
      horizontal 10 cm visual analogue scale (VAS), C-reactive protein (CRP) and the
      HAQ, were carried out 0, 6, 12 and 24 weeks after treatment had been started. Any
      comorbid condition likely to affect the HAQ was noted. RESULTS: Eighteen patients
      completed the 6-month assessment period. These included four males and 14
      females, with a mean age of 68.5 years. Pretreatment mean disease activity showed
      EMS of 68 min, VAS pain of 69 mm, CRP of 46 mg/l and a HAQ score of 1.57. At 6
      months, mean EMS had declined to 4 min, VAS pain to 11 mm, CRP to 9 mg/l and the
      HAQ score to 0.14. Linear regression analysis of HAQ vs EMS, VAS and CRP showed
      correlation coefficients of 0.72, 0.66 and 0.63, respectively. Standardized
      response means (SRM), a measure of responsiveness, for HAQ, EMS, VAS and CRP were
      3, 1.7, 1. 8 and 1.6, respectively. We assessed each section of the HAQ
      individually to see if any particular daily activity was more responsive to
      change. Questions on dressing and grooming, rising and eating were more
      responsive to change (SRM 2.5, 2.7 and 1.8, respectively) than questions about
      walking, hygiene, reach, grip and activities (SRM 0.8, 1.4, 1.2, 1.1 and 1.1,
      respectively). CONCLUSION: The HAQ is useful in the assessment of functional
      status in PMR, is responsive to change and correlates well with conventional
      indices of disease activity. However, fixed disabilities like osteoarthritis,
      shoulder capsulitis and systemic diseases may affect its interpretation. The
      sections of the HAQ measuring disability related to inflammatory
      stiffness/proximal involvement showed greater responsiveness to change than other
      sections, and hence may have a greater role in evaluating disease activity in
      PMR.

PMID- 10952745
TI  - Development of lupus-related side-effects in patients with early RA during
      sulphasalazine treatment-the role of IL-10 and HLA.
AB  - OBJECTIVE: The development of systemic lupus erythematosus (SLE)-related
      syndromes during treatment with sulphasalazine has been described and
      demonstrated to be influenced by genetic factors. The prevalence of this drug
      induced condition and the immunological mechanisms involved are less known. The
      aim of this study was to determine the prevalence of sulphasalazine-induced lupus
      like reactions in a well-defined early rheumatoid arthritis (RA) cohort and to
      analyse the roles of HLA haplotypes, autoantibodies and the B-cell stimulating
      cytokine interleukin-10 (IL-10) as possible underlying risk factors. Patients and
      methods. Forty-one consecutive patients with early RA, in whom sulphasalazine was
      used as the first disease-modifying anti-rheumatic drug in single therapy and was
      maintained for at least 6 months, were investigated for the occurrence of lupus
      related events. Longitudinal analyses of rheumatoid factor (RF), antinuclear
      antibodies (ANA), anti-double-stranded DNA antibodies and serum IL-10 (ELISA) and
      the typing of HLA DR and DQ alleles were performed. RESULTS: Four of the 41
      patients developed lupus-like disease. Three of four patients who had lupus
      related events vs four of 37 patients without side-effects had an HLA DR 0301
      haplotype. The patients developing lupus-related side-effects had increased
      levels of serum IL-10 and a high frequency of ANA in speckled patterns before the
      onset of therapy. CONCLUSION: The development of SLE-like symptoms and SLE
      related autoantibody production was observed more commonly than expected, with an
      increased risk in patients with SLE-related HLA haplotypes, increased serum IL-10
      levels and ANA in speckled patterns. The data suggest that immunomodulation
      associated with sulphasalazine treatment may contribute to the development of
      lupus-related reactions in genetically predisposed individuals.

PMID- 10952746
TI  - Long-term efficacy of radon spa therapy in rheumatoid arthritis--a randomized,
      sham-controlled study and follow-up.
AB  - OBJECTIVE: To quantify the efficacy of a series of baths containing natural radon
      and carbon dioxide (1.3 kBq/l, 1.6 g carbon dioxide/l on average) versus
      artificial carbon dioxide baths alone in patients with rheumatoid arthritis.
      SUBJECTS: Sixty patients participating in an in-patient rehabilitation programme
      including a series of 15 baths were randomly assigned to two groups. DESIGN: Pain
      intensity (100 mm visual analogue scale) and functional restrictions [Keitel
      functional test, Arthritis Impact Measurement Scales (AIMS questionnaire)] were
      measured at baseline, after completion of treatment and 3 and 6 months
      thereafter. To investigate whether the overall value of the outcomes was the same
      in both groups, the overall mean was analysed by Student's t-test for independent
      samples. RESULTS: The two groups showed a similar baseline situation. After
      completion of treatment, relevant clinical improvements were observed in both
      groups, with no notable group differences. However, the follow-up revealed
      sustained effects in the radon arm, and a return to baseline levels in the sham
      arm. After 6 months, marked between-group differences were found for both end
      points (pain intensity: -16.9%, 95% confidence interval -27.6 to -6.2%; AIMS
      score: 0.57, 95% confidence interval 0.16 to 0.98). The between-group differences
      were statistically significant for both overall means (pain intensity, P: = 0.04;
      AIMS, P: = 0.01). CONCLUSION: Marked short-term improvements in both groups at
      the end of treatment may have masked potential specific therapeutic effects of
      radon baths. However, after 6 months of follow-up the effects were lasting only
      in patients of the radon arm. This suggests that this component of the
      rehabilitative intervention can induce beneficial long-term effects.

PMID- 10952747
TI  - Antibodies to parvovirus B19 non-structural protein are associated with chronic
      but not acute arthritis following B19 infection.
AB  - OBJECTIVE: To determine the incidence and significance of antibodies to the
      parvovirus B19 non-structural (NS1) protein in B19-infected persons during acute
      infection and convalescence. METHODS: The B19 NS1 protein was expressed in SF9
      cells using the baculovirus expression system and was used to prepare
      immunofluorescence slides. These were used in a fluorescent antibody test to
      determine anti-B19 NS1 IgG in a well-characterized cohort of 53 persons at the
      time of acute B19 infection and again after a follow-up period of 26-85 months.
      Results were examined for statistical significance by the use of Fisher's exact
      test. RESULTS: NS1 antibodies were detected in five of 32 persons with acute B19
      infection (four with arthritis) and 10 of 53 persons with past B19 infection (six
      with chronic arthritis and two with chronic arthritis and chronic fatigue
      syndrome). Regarding the correlation of NS1 antibodies and arthritis, at the time
      of acute infection four of 24 persons with arthritis had NS1 antibodies detected
      compared with one of eight persons with any other symptoms (P: = 1). During
      convalescence, eight of 20 persons with chronic arthritis had NS1 antibodies
      compared with two of 33 with symptoms of any other category (all except one were
      asymptomatic) (P: = 0.007). All 10 patients with NS1 antibodies during
      convalescence had arthritis during acute infection, which persisted in eight
      persons until the time of follow-up. CONCLUSION: Antibodies to parvovirus B19 NS1
      protein are associated with chronic but not with acute arthritis after B19
      infection.

PMID- 10952749
TI  - Respiratory failure due to muscle weakness in inflammatory myopathies:
      maintenance therapy with home mechanical ventilation.
AB  - Polymyositis and dermatomyositis are idiopathic inflammatory myopathies.
      Respiratory complications are a common feature, but ventilatory insufficiency is
      rare in these patients. We describe here three patients diagnosed with
      inflammatory myopathy (polymyositis) with respiratory failure due to muscle
      weakness who did not respond to immunosuppressive therapy. Mechanical ventilation
      at home with nasal or tracheal intermittent positive pressure resulted in
      improved chronic hypoventilation. This treatment improves the quality of life of
      patients with inflammatory myopathies and can be lifesaving in some cases.

PMID- 10952748
TI  - Reliability and sensitivity to change of various measures of hand function in
      relation to treatment of synovitis of the metacarpophalangeal joint in rheumatoid
      arthritis.
AB  - OBJECTIVES: The reliability and discriminative capacity of hand function tests
      were studied in order to obtain tests suitable for the evaluation of local
      treatment of an arthritic metacarpophalangeal (MCP) joint. METHODS: To assess
      reliability, hand function tests were measured twice without local treatment of
      the MCP in 25 patients with rheumatoid arthritis (RA). The discriminative
      capacity of the hand function tests with respect to the results of intra
      articular corticosteroid injection was assessed in 28 RA patients with synovitis
      of an MCP joint. Thereafter, a randomized, observer-blind treatment study was
      performed in 21 RA patients with synovitis of an MCP joint; 10 of the patients
      were treated. Results/Conclusions. This study showed that the efficacy of
      treatment of an MCP joint can be measured by several reliable and discriminative
      parameters: passive flexion, the Ritchie pain score, swelling, the Arthritis
      Impact Measurements Scales question about buttoning clothes, and visual analogue
      scale questions about the activity of the disease and swelling of the joint.

PMID- 10952750
TI  - Abnormal microcirculation and temperature in skin above tender points in patients
      with fibromyalgia.
AB  - OBJECTIVE: Skin temperature and skin blood flow were studied above different
      tender points in 20 patients with fibromyalgia (FM) and 20 healthy controls.
      METHODS: Blood flow was measured by laser Doppler flowmetry and skin temperature
      was measured with an infrared thermometer. RESULTS: In the skin above the five
      tender points examined in each subject, we found an increased concentration of
      erythrocytes, decreased erythrocyte velocity and a consequent decrease in the
      flux of erythrocytes. A decrease in temperature was recorded above four of the
      five tender points. CONCLUSION: Vasoconstriction occurs in the skin above tender
      points in FM patients, supporting the hypothesis that FM is related to local
      hypoxia in the skin above tender points.

PMID- 10952751
TI  - Virus-associated vasculitides.

PMID- 10952752
TI  - Vasculitis and the antiphospholipid syndrome.

PMID- 10952753
TI  - Osteomyelitis of the humerus following steroid injections for tennis elbow.

PMID- 10952754
TI  - Sclerosing injections for chronic low back pain.

PMID- 10952755
TI  - Sclerosing injections in patients with chronic low back pain.

PMID- 10952756
TI  - Teaching of musculoskeletal diseases to undergraduates in the Faculty of
      Medicine, Kuwait University.

PMID- 10952757
TI  - Acquired haemophilia and PM-Scl antibodies.

PMID- 10952759
TI  - Dehydroepiandrosterone in the treatment of systemic lupus erythematosus.

PMID- 10952758
TI  - Retinal artery occlusion in Wegener's granulomatosis.

PMID- 10952761
TI  - Robin goodfellow

PMID- 10952762
TI  - Announcements

PMID- 10952760
TI  - Psoriatic arthritis, nail disease and pustules following Hodgkin's lymphoma.

PMID- 10952763
TI  - Forthcoming events

PMID- 10952764
TI  - Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted
      region, generation of a PAC/BAC contig and identification of candidate genes. UK
      Cancer Cytogenetics Group (UKCCG).
AB  - Deletion of the long arm of chromosome 20 represents the most common chromosomal
      abnormality associated with the myeloproliferative disorders (MPDs) and is also
      found in other myeloid malignancies including myelodysplastic syndromes (MDS) and
      acute myeloid leukaemia (AML). Previous studies have identified a common deleted
      region (CDR) spanning approximately 8 Mb. We have now used G-banding, FISH or
      microsatellite PCR to analyse 113 patients with a 20q deletion associated with a
      myeloid malignancy. Our results define a new MPD CDR of 2.7 Mb, an MDS/AML CDR of
      2.6 Mb and a combined 'myeloid' CDR of 1.7 Mb. We have also constructed the most
      detailed physical map of this region to date--a bacterial clone map spanning 5 Mb
      of the chromosome which contains 456 bacterial clones and 202 DNA markers. Fifty
      one expressed sequences were localized within this contig of which 37 lie within
      the MPD CDR and 20 within the MDS/AML CDR. Of the 16 expressed sequences (six
      genes and 10 unique ESTs) within the 'myeloid' CDR, five were expressed in both
      normal bone marrow and purified CD34 positive cells. These data identify a set of
      genes which are both positional and expression candidates for the target gene(s)
      on 20q.

PMID- 10952765
TI  - Autosomal dominant type IIa hypercholesterolemia: evaluation of the respective
      contributions of LDLR and APOB gene defects as well as a third major group of
      defects.
AB  - Autosomal dominant type IIa hypercholesterolaemia (ADH) is characterised by an
      elevation of total plasma cholesterol associated with increased LDL particles.
      Numerous different molecular defects have been identified in the LDL receptor
      (LDLR) and few specific mutations in the apolipoprotein B (APOB) gene resulting
      in familial hypercholesterolaemia and familial defective apoB-100 respectively.
      To estimate the respective contribution of LDLR, APOB and other gene defects in
      this disease, we studied 33 well characterised French families diagnosed over at
      least three generations with ADH through the candidate gene approach. An
      estimation of the proportions performed with the HOMOG3R program showed that an
      LDLR gene defect was involved in approximately 50% of the families (P = 0.001).
      On the other hand, the estimated contribution of an APOB gene defect was only
      15%. This low estimation of ADH due to an APOB gene defect is further
      strengthened by the existence of only two probands carrying the APOB (R3500Q)
      mutation in the sample. More importantly and surprisingly, 35% of the families in
      the sample were estimated to be linked to neither LDLR nor APOB genes. These data
      were confirmed by the exclusion of both genes through direct haplotyping in three
      families. Our results demonstrate that the relative contributions of LDLR and
      APOB gene defects to the disease are very different. Furthermore, our results
      also show that genetic heterogeneity is, generally, underestimated in ADH, and
      that at least three major groups of defects are involved. At this point, the
      contribution of the recently mapped FH3 gene to ADH cannot be assessed nor its
      importance in the group of 'non LDLR/non APOB' families.

PMID- 10952766
TI  - On salvaging the pharmaceutical sciences in Canada?

PMID- 10952767
TI  - The Institute for Biomolecular Design.

PMID- 10952768
TI  - Anticholinergic drugs used in Parkinson's disease: An overlooked class of drugs
      from a pharmacokinetic perspective.
AB  - Anticholinergic drugs were the first pharmacological agents used in the treatment
      of Parkinson"s disease. Although levodopa and other centrally acting dopaminergic
      agonists have largely supplanted their use, they still have a place in treatment
      of the disease. As a therapeutic class, there is little pharmacokinetic
      information available for these drugs, which is inclusive of benztropine,
      biperiden, diphenhydramine, ethopropazine, orphenadrine, procyclidine and
      trihexyphenidyl. Pharmacokinetic information is largely restricted to studies
      involving young health volunteers given single doses. In general, this class of
      drugs is rapidly absorbed after oral administration to humans. Oral
      bioavailability is variable between the different drugs, ranging from 30% to over
      70%. Each of the drugs appears to possess a large Vd in humans and animals, and
      distribution to tissues is rapid. The drugs are all characterized by relatively
      low clearance relative to hepatic blood flow, and appear to be extensively
      metabolized, primarily to N-dealkylated and hydroxylated metabolites. The
      available information suggests that excretion of parent drug and metabolite is
      via the urine and bile. Although the existence of a plasma concentration vs.
      therapeutic effect relationship has not been explored, there is some evidence
      suggesting a relationship between concentration and peripheral side effects.
      Elderly tolerate the drugs less well than do younger patients. There is a notable
      lack of pharmacokinetic information for these drugs in the elderly. The lack of
      pharmacokinetic information for multiple dose administration and in the elderly
      may be a possible hindrance in the safe and effective use of these drugs in
      patients with Parkinson"s disease.

PMID- 10952770
TI  - Polymeric films as vehicle for buccal delivery: swelling, mechanical, and
      bioadhesive properties.
AB  - PURPOSE: To investigate the suitability of an SCMC (sodium carboxymethyl
      cellulose/polyethylene glycol 400/carbopol 934P) and an HPMC (hydroxypropylmethyl
      cellulose/polyethylene glycol 400/carbopol 934P) films as drug vehicle for buccal
      delivery. METHODS: The mechanical and in vitro bioadhesive strength properties of
      the films were investigated using texture analyzer equipment, while swelling
      behavior was studied in different media, namely, distilled water and simulated
      saliva solution. In addition, the in vivo bioadhesion of the film was studied by
      estimating the film residence time on buccal mucosa of human volunteers. RESULTS:
      Increase in carbopol 934P content was found to elevate the elasticity, softness
      and bioadhesive strength but decrease the strength and degree of swelling of both
      SCMC and HPMC films. SCMC films swelled more extensively in distilled water while
      HPMC films in simulated saliva solution. HPMC films exhibited greater in vivo
      bioadhesion although the in vitro bioadhesive strength was lower than SCMC films.
      Correlation existed between the in vivo and in vitro bioadhesion data within the
      polymer, but no rank correlation was observed between the two polymers.
      CONCLUSION: HPMC films may be preferred over SCMC films as drug vehicle for
      buccal delivery as the former was tougher, more elastic, more bioadhesive in vivo
      and swelled in a more tolerable manner in the oral cavity than the latter.

PMID- 10952769
TI  - Cytochrome P450 3A4 in vivo ketoconazole competitive inhibition: determination of
      Ki and dangers associated with high clearance drugs in general.
AB  - Assuming complete hepatic substrate metabolism and system linearity, quantitative
      effects of in vivo competitive inhibition are investigated. Following oral
      administration of a substrate in the presence of a competitive inhibitor,
      determination of the inhibition constant (Ki) is possible when plasma
      concentration-time profiles of both substrate and inhibitor are available. When
      triazolam is the P450 3A4 substrate and ketoconazole the competitive inhibitor,
      Ki approximately 1.2 microg/mL in humans. The effects of competitive inhibition
      can be divided into two components: first-pass hepatic metabolism and systemic
      metabolism. For drugs with high hepatic extraction ratios, the impact of
      competitive inhibition on hepatic first-pass metabolism can be particularly
      dramatic. For example, human terfenadine hepatic extraction goes from 95% in the
      absence of a competitive inhibitor to 35% in the presence of one (ketoconazole,
      200 mg po Q 12 h dosed to steady-state). First-pass extraction therefore goes
      from 5% in the absence of the inhibitor to 65% in its presence. The combined
      effect on first-pass and systemic metabolism produces an approximate 37 fold
      increase in terfenadine area under the plasma concentration-time curve. Assuming
      intact drug is active and/or toxic, development of metabolized drugs with
      extensive first-pass metabolism should be avoided if possible, since inhibition
      of metabolism may lead to profound increases in exposure.

PMID- 10952771
TI  - Serum midkine levels are increased in patients with various types of carcinomas.
AB  - The level of expression of midkine (MK), a heparin-binding growth factor, is
      increased in many types of human carcinomas. An enzyme-linked immunoassay, which
      utilizes a combination of rabbit and chicken antibodies revealed that serum MK
      level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with
      an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly
      elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed
      levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a
      similar profile of serum MK level. There was no or weak correlation between C
      reactive protein level, a marker of inflammation, and serum MK level.
      Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage
      I carcinoma already showed elevated serum MK levels. The present results
      indicated that serum MK could serve as a general tumour marker with a good
      potential for clinical application.

PMID- 10952772
TI  - Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II
      study of three different doses. Gem Vin Investigators.
AB  - Our aim was to study the activity and toxicity of the gemcitabine plus
      vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously
      untreated patients aged < 70 years, with stage IV or IIIb (not candidates for
      radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of
      Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I =
      1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A
      feasibility study was performed at each dose-level, followed by a single-stage
      phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia.
      Overall, out of 126 patients enrolled in phase II studies, there were one
      complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response
      rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The
      treatment was well tolerated. Toxicity was less frequent and severe at level I.
      Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life
      analysis showed that patients with a worse baseline global health status score
      tended to drop out of the study earlier than those with a better score. Gem Vin
      is feasible at different doses. It is sufficiently active and well tolerated. A
      phase III study to compare the effect on quality of life of Gem Vin (level I) vs
      cisplatin-based chemotherapy is ongoing.

PMID- 10952773
TI  - Treatment of advanced medullary thyroid cancer with an alternating combination of
      doxorubicin-streptozocin and 5 FU-dacarbazine. Groupe d'Etude des Tumeurs a
      Calcitonine (GETC).
AB  - Combinations of doxorubicin and streptozocin and 5-FU and dacarbazine were given
      alternately to 20 patients with metastatic medullary thyroid carcinoma. Three
      partial responses and 10 long-term stabilizations were observed. No unexpected
      toxicity occurred.

PMID- 10952774
TI  - Prevalence of BRCA1 in a hospital-based population of Dutch breast cancer
      patients.
AB  - The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch
      breast cancer patients not selected for family history or age at diagnosis. They
      were tested for germline mutations in the BRCA1 gene using an assay which detects
      small deletions and insertions (DSDI), as well as the two major genomic founder
      deletions present in the Dutch population. Data on family history and bilateral
      breast cancer were obtained retrospectively. Ten protein truncating mutations
      were detected and one in-frame deletion with an unknown relation to disease risk.
      Four patients carried the Dutch founder deletion of exon 22. Based on these
      results the estimated prevalence of breast cancer in the general population in
      the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age
      and under 50 years-of-age this prevalence is 9.5% and 6. 4%, respectively. All
      mutation carriers were under 50 years-of-age at diagnosis of the first breast
      cancer, and five did not have any relative with breast cancer. The proportions of
      bilateral breast cancer in the mutation carriers and non-carriers did not differ
      from each other. These data indicate that in the general Dutch breast cancer
      population the great majority of BRCA1 mutations will be found in women diagnosed
      under 50 years-of-age.

PMID- 10952775
TI  - Serial analysis of gene expression identifies putative metastasis-associated
      transcripts in colon tumour cell lines.
AB  - We have used serial analysis of gene expression (SAGE) to identify gene
      expression differences between a primary colon tumour cell line (SW480) and an
      isogenic lymph-node metastasis cell line (SW620). Differential expression was
      confirmed for the following genes: keratin K5, cystatin S, serum amyloid A, the
      human homologue of yeast ribosomal S28 and the p32 subunit of human pre-mRNA
      splicing factor SF2. Expression of confirmed differences were also analysed in
      other metastatic cell lines.

PMID- 10952776
TI  - Allelic losses in carcinoma in situ and testicular germ cell tumours of
      adolescents and adults: evidence suggestive of the linear progression model.
AB  - Testicular germ cell tumours (TGCTs) may arise through a process of multi-step
      carcinogenesis, and loss of heterozygosity (LOH) at specific loci is likely to be
      an important early event, although this has not been studied in detail. In order
      to explore the pathogenetic relationships among TGCTs, we investigated the
      genetic changes in testicular tumours that exhibit a disease continuum through
      the precursor carcinoma in situ (CIS) to either seminoma (SE) and/or non
      seminomatous germ cell tumour (NSGCT). Universal amplification has been performed
      on 87 TGCT specimens and 36 samples of CIS cells microdissected from single
      paraffin-embedded tumour sections from 40 patients, including multiple specimens
      of CIS and TGCT cells of varied histology microdissected from 24 individual
      patients. Seventy-seven microsatellite markers were used to assay these samples
      for LOH at candidate regions selected from the literature, mapping to 3q, 5q, 9p,
      11p, 11q, 12q, 17p and 18q. Construction of deletion maps for each of these
      regions identified common sites of deletion at 3q27-q28, 5q31, 5q34-q35, 9p22-p21
      and 12q22, which correlate with allelic losses we have also observed in the
      precursor CIS cells. Evidence for allelic loss at 3q27-q28 was observed in all of
      the embryonal carcinoma samples analysed. We conclude that inactivation of
      gene(s) within these regions are likely to be early events in the development and
      progression of TGCTs. These results also provide molecular evidence in support of
      the hypothesis that SE is an intermediate stage of development within a single
      neoplastic pathway of progression from CIS precursor cells to NSGCT.

PMID- 10952777
TI  - BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast
      cancer patients.
AB  - To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not
      been characterized in the Turkish population. We investigated the presence of
      BRCA mutations in 53 individuals with a personal and family history of breast
      and/or ovarian cancer, and 52 individuals with a personal history of breast
      cancer diagnosed below age 50 without additional family history. We have
      identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques
      involving protein truncation test, direct sequencing and heteroduplex analysis.
      We found eight out of 53 patients (15.1%) with a family history to carry BRCA
      gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43
      families presenting only breast cancer histories, and four were found in families
      presenting ovarian cancer with or without breast cancer. We also demonstrated two
      BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer
      cases without additional family history. Three of nine BRCA1 and both BRCA2
      mutations detected in this study were not reported previously. These mutations
      may be specific to the Turkish population. The BRCA1 5382insC mutation, specific
      to Ashkenazi and Russian populations, was found twice in our study group,
      representing a possible founder mutation in the Turkish population.

PMID- 10952779
TI  - Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma.
AB  - Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22-q23 in
      several types of tumours of diverse cell origin. Previous investigations of LOH
      at this chromosomal region in colorectal carcinoma have been contradictory in
      their findings, and have only included between 1-4 loci. In order to define any
      regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on
      the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal
      carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the
      highest frequencies of LOH at D11S1340 (41.0%), located between 105.13-111.97 Mb
      from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located
      approximately 113 Mb from the centromere. No statistically significant
      associations between LOH and age-of-presentation or Dukes' stage were found. LOH
      was observed in colorectal tumours of all Dukes' stages, including Dukes' stages
      A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23
      occurs in the early stages of colorectal carcinoma. These results confirm the
      presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in
      the carcinogenesis of colorectal carcinoma, and will facilitate future
      identification of candidate genes.

PMID- 10952778
TI  - Identification of nucleolar protein No55 as a tumour-associated autoantigen in
      patients with prostate cancer.
AB  - Four different genes were identified by immunoscreening of a cDNA expression
      library from the human prostate cancer cell line DU145 with allogeneic sera from
      four prostate cancer patients. A cDNA encoding the nucleolar protein No55 was
      further analysed and shown to be expressed at the mRNA level in several normal
      tissues, including ovaries, pancreas and prostate and in human prostate cancer
      cell lines PC-3, PC-3m and LNCaP. By reverse transcriptase/polymerase chain
      reaction, expression of No55 was several-fold higher in two out of nine prostate
      cancer primary tumours and two out of two metastatic lesions, compared to normal
      prostate tissue. Antibodies to No55 were detected in sera from seven out of 47
      prostate cancer patients but not in sera from 20 healthy male controls. Sequence
      analysis of the No55 open reading frame from normal and tumour tissues revealed
      no tumour-specific mutations. The No55 gene was located to chromosome 17q21, a
      region reported to be partially deleted in prostate cancer. Considering the
      immunogenicity of the No55 protein in the tumour host, the expression profile and
      chromosomal localization of the corresponding gene, studies evaluating No55 as a
      potential antigen for immunological studies in prostate cancer may be warranted.

PMID- 10952780
TI  - CTGF (IGFBP-rP2) is specifically expressed in malignant lymphoblasts of patients
      with acute lymphoblastic leukaemia (ALL).
AB  - Connective tissue growth factor (CTGF) is a major chemotactic and mitogenic
      factor for connective tissue cells. The amino acid sequence shares an overall 28
      38% identity to IGFBPs and contains critical conserved sequences in the amino
      terminus. It has been demonstrated that human CTGF specifically binds IGFs with
      low affinity and is considered to be a member of the IGFBP superfamily (IGFBP
      rP2). In the present study, the expression of CTGF (IGFBP-rP2) in human leukaemic
      lymphoblasts from children with acute lymphoblastic leukaemia (ALL) was
      investigated. RNA samples from tumour clones enriched by ficoll separation of
      bone marrow or peripheral blood mononuclear cells (MNC) from 107 patients with
      childhood ALL at diagnosis and 57 adult patients with chronic myeloid leukaemia
      (CML) were studied by RT-PCR. In addition MNC samples from children with IDDM and
      cord blood samples from healthy newborns were investigated as control groups.
      Sixty-one percent of the patients with ALL (65 of 107) were positive for CTGF
      (IGFBP-rP2) expression. In the control groups, no expression of CTGF (IGFBP-rP2)
      in peripheral MNC was detected, and in the group of adult CML patients only 3.5%
      (2 of 57) were positive for this gene. The role of CTGF (IGFBP-rP2) in
      lymphoblastic leukaemogenesis requires further evaluation, as does its potential
      utility as a tumour marker.

PMID- 10952781
TI  - Prostate tumours from an Asian population: examination of bax, bcl-2, p53 and ras
      and identification of bax as a prognostic marker.
AB  - Molecular studies have suggested that ethnicity may play a significant role in
      prostate tumorigenesis, but no information exists for groups other than Caucasian
      or Japanese patients. We examined 62 archival samples of prostate tumours from
      Asians of non-Japanese origin for the over-expression of p53, for the possible
      presence of mutated ras genes, for the overexpression of the bcl-2 and bax
      proteins, as well as directly for the presence of apoptotic cells by the TUNEL
      methodology. Gene lesions of both ras (0%) and p53 (3%) were rare. While bcl-2
      expression was not observed in any sample, bax expression was noted in 76% of
      samples and was associated with a significantly worse patient prognosis both
      overall (P< 0.005) and specifically in Chinese patients (P< 0.02). Apoptotic
      cells were found in 61% of samples, and were significantly associated with the
      presence of bax expression (P = 0.002), but not patient survival. These results
      suggest that prostate tumours from non-Japanese Asians are genetically distinct
      from prostate tumour found in both Japanese and Caucasian patients, and that
      treatment modalities may need to be tailored for specific population groups.

PMID- 10952782
TI  - Increased expression of S100A6 at the invading fronts of the primary lesion and
      liver metastasis in patients with colorectal adenocarcinoma.
AB  - Two members of the S100 gene family, S100A6 and S100A4 have been suggested to be
      associated with cancer invasion and metastasis. To study their involvement in the
      malignancy of human colorectal adenocarcinoma, we examined the protein expression
      levels of S100A6 and S100A4 in the primary colorectal adenocarcinoma (T) and
      paired adjacent normal colorectal mucosa (N) from 12 cases, quantitatively by
      Western blot analysis. In 11 of 12 and seven of 12 cases, S100A6 and S100A4
      expression levels were higher in T than in N, respectively. Average S100A6 level
      in T was significantly higher than in N (about x 2.3;P = 0.001), whereas average
      S100A4 level in T was not. When S100A6 expression levels in three sets of matched
      samples of primary colorectal adenocarcinoma (T) and liver metastasis (M) were
      examined, S100A6 levels were higher in M than in T in two of three cases.
      Immunohistochemical analysis using monoclonal anti-S100A6 antibody showed that 23
      of 42 (55%) primary colorectal adenocarcinoma and 15 of 16 (94%) liver metastasis
      specimens were positively stained. S100A6 immunostaining of primary colorectal
      adenocarcinomas was significantly more intense in the invading fronts with
      structural atypia than in central portions with glandular structure (P< 0.0001),
      whereas Ki-67 staining (a growth marker) was similar in these two portions.
      Interestingly, S100A6 and Ki-67 immunostaining patterns in liver metastases were
      also the same as in primary lesions. These results suggest that S100A6 is
      involved in the invasive process of human colorectal adenocarcinomas and that
      S100A6 expression levels decrease when carcinoma cells form glandular structure
      again at the central portions of metastatic nodules.

PMID- 10952783
TI  - Prognostic value of vascular endothelial growth factor (VEGF) in head and neck
      squamous cell carcinomas.
AB  - Vascular endothelial growth factor (VEGF) has been identified as the substance
      that increases the permeability and proliferation of vascular endothelial cells.
      We examined the clinical significance of VEGF expression in 60 head and neck
      squamous cell carcinomas using the methods of Western blot, immunohistochemistry,
      and reverse transcriptase-polymerase chain reaction (RT-PCR), comparatively, and
      analysed the relationship between VEGF status in Western blot and tumour size,
      lymph-node status, histologic grade and disease-free survival (DFS) rate. Western
      blot analysis revealed high VEGF expressors (tumour/normal tissue density >/= 3
      fold) in 26 patients (43%) and low VEGF expressors (< 3-fold) in 34 patients
      (57%). The results of the Western blot analysis correlated significantly with
      those of the RT-PCR (P = 0.00007) or immunohistochemistry (P = 0. 00006). High
      VEGF expressors are associated with the progression of lymph-node spread (P =
      0.0009), which are correlated with poor DFS. The 2-year DFS rate of high VEGF
      expressors (30%) was significantly lower than that of low VEGF expressors (78%)
      (P = 0.0008). Multivariate analysis showed VEGF expression and stage were
      independent predictors for the DFS (P = 0.045 and 0.041, respectively). VEGF
      expression may play an important role in progression of HNSCC.

PMID- 10952784
TI  - Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast
      cancer cell lines.
AB  - An inverse relationship between protein kinase C (PKC) activity and oestrogen
      receptor (ER) expression in human breast cell lines and tumours has been firmly
      established over the past 10 years. To determine whether specific alterations in
      PKC expression accompany hormone-independence, we examined the expression of PKC
      isozymes in the hormone-independent human breast cancer cell clones MCF-7 5C and
      T47D:C42 compared with their hormone-dependent counterparts, MCF-7 A4, MCF-7 WS8
      and T47D:A18 respectively. Both hormone-independent cell clones exhibit elevated
      PKC alpha expression and increased basal AP-1 activity compared with the hormone
      dependent cell clones. To determine whether PKC alpha overexpression is
      sufficient to mediate the hormone-independent phenotype, we stably transfected an
      expression plasmid containing PKC alpha cDNA to the T47D:A18 and MCF-7 A4 cell
      lines. This is the first report of PKC alpha transfection in T47D cells. In
      contrast to MCF-7 cells, T47D has the propensity to lose the ER and more readily
      forms tamoxifen-stimulated tumours in athymic mice. We find that in T47D:A18/PKC
      alpha clones, there is concomitant up-regulation of PKC beta I and delta, whereas
      in the MCF-7 A4/PKC alpha transfectants PKC epsilon is up-regulated. In T47D:A18,
      but not in MCF-7 A4, PKC alpha stable transfection is accompanied by down
      regulation of ER function whilst basal AP-1 activity is elevated. Our results
      suggest PKC alpha overexpression may play a role in growth signalling during the
      shift from hormone dependent to hormone-independent breast cancers.

PMID- 10952785
TI  - Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the
      thymidylate synthase (TS) inhibitor ZD9331.
AB  - Uracil DNA misincorporation and misrepair of DNA have been recognized as
      important events accompanying thymidylate synthase (TS) inhibition. dUTPase
      catalyses the hydrolysis of dUTP to dUMP, thereby maintaining low intracellular
      dUTP. We have addressed the relationship between dUTPase expression and cellular
      sensitivity to TS inhibition in four human lung tumour cell lines. Sensitivity (5
      day MTT assay) to the growth inhibitory effects of the non-polyglutamatable,
      specific quinazoline TS inhibitor ZD9331, varied up to 20-fold (IC(50)3-70 nM).
      TS protein expression correlated with TS activity (r(2)= 0.88, P = 0.05).
      Intracellular concentrations of drug following exposure to ZD9331 (1 microM, 24
      h) varied by approximately 2-fold and dTTP pools decreased by > 80% in all cell
      lines. No clear associations across the cell lines between intracellular drug
      concentrations, TS activity/expression, or TTP depletion could be made. dUTPase
      activity varied 17-fold and correlated with dUTPase protein expression (r(2)=
      0.94, P = 0.03). There was a striking variation in the amount of dUTP formed
      following exposure to ZD9331 (between 1.3 and 57 pmole 10(-6)cells) and was in
      general inversely associated with dUTPase activity. A large expansion in the dUTP
      pool was associated with increased sensitivity to a 24-h exposure to ZD9331 in
      A549 cells that have low dUTPase activity/expression. dUTPase expression and
      activity were elevated (approximately 3-fold) in two variants of a human
      lymphoblastoid cell line with acquired resistance to TS inhibitors, further
      suggesting an important role for this enzyme in TS inhibited cells.

PMID- 10952786
TI  - Single amino acid (arginine) deprivation: rapid and selective death of cultured
      transformed and malignant cells.
AB  - The effects of arginine deprivation (-Arg) has been examined in 26 cell lines.
      Less than 10% of those with transformed or malignant phenotype survived for > 5
      days, and many died more rapidly, notably leukaemic cells. Bivariate flow
      cytometry confirmed that vulnerable cell lines failed to move out of cell cycle
      into a quiescent state (G0), but reinitiated DNA synthesis. Many cells remained
      in S-phase, and/or had difficulty progressing through to G2 and M. Two tumour
      lines proved relatively 'resistant', A549 and MCF7. Although considerable cell
      loss occurred initially, both lines showed a 'cell cycle freeze', in which cells
      survived for > 10 days. These cells recovered their proliferative activity in
      +Arg medium, but behaved in the same manner to a second -Arg episode as they did
      to the first episode. In contrast, normal cells entered G0 and survived in -Arg
      medium for several weeks, with the majority of cells recovering with predictable
      kinetics in +Arg medium. In general, cells from a wide range of tumours and
      established lines die quickly in vitro following -Arg treatment, because of
      defective cell cycle checkpoint stringency, the efficacy of the treatment being
      most clearly demonstrated in co-cultures in which only the normal cells survived.
      The findings demonstrate a potentially simple, effective and non-genotoxic
      strategy for the treatment of a wide range of cancers.

PMID- 10952787
TI  - Determinants of anti-vascular action by combretastatin A-4 phosphate: role of
      nitric oxide.
AB  - The anti-vascular action of the tubulin binding agent combretastatin A-4
      phosphate (CA-4-P) has been quantified in two types of murine tumour, the breast
      adenocarcinoma CaNT and the round cell sarcoma SaS. The functional vascular
      volume, assessed using a fluorescent carbocyanine dye, was significantly reduced
      at 18 h after CA-4-P treatment in both tumour types, although the degree of
      reduction was very different in the two tumours. The SaS tumour, which has a
      higher nitric oxide synthase (NOS) activity than the CaNT tumour, showed
      approximately 10-fold greater resistance to vascular damage by CA-4-P. This is
      consistent with our previous findings, which showed that NO exerts a protective
      action against this drug. Simultaneous administration of CA-4-P with a NOS
      inhibitor, N(omega)-nitro-L-arginine (L-NNA), resulted in enhanced vascular
      damage and cytotoxicity in both tumour types. Administration of diethylamine NO,
      an NO donor, conferred protection against the vascular damaging effects.
      Following treatment with CA-4-P, neutrophil infiltration into the tumours,
      measured by myeloperoxidase (MPO) activity, was significantly increased. Levels
      of MPO activity also correlated with the levels of vascular injury and
      cytotoxicity measured in both tumour types. Neutrophilic MPO generates free
      radicals and may therefore contribute to the vascular damage associated with CA-4
      P treatment. MPO activity was significantly increased in the presence of L-NNA,
      suggesting that the protective effect of NO against CA-4-P-induced vascular
      injury may be, at least partially, mediated by limiting neutrophil infiltration.
      The data are consistent with the hypothesis that neutrophil action contributes to
      vascular injury by CA-4-P and that NO generation acts to protect the tumour
      vasculature against CA4-P-induced injury. The protective effect of NO is probably
      associated with an anti-neutrophil action.

PMID- 10952788
TI  - P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of
      cyclin E by the histone deacetylase inhibitor FR901228.
AB  - Depsipeptide, FR901228, a novel cyclic peptide inhibitor of histone deacetylase
      with a unique cytotoxicity profile is currently in phase I clinical trials. Here
      we demonstrate that, in addition to G2/M arrest, FR901228 causes G1 arrest with
      Rb hypophosphorylation. In vitro kinase assays demonstrated no direct inhibition
      of CDK activity, however, an inhibition was observed in CDKs extracted from cells
      exposed to FR901228. Cyclin D1 protein disappeared between 6 and 12 hours after
      treatment with FR901228, whereas cyclin E was upregulated. While it did not
      induce wt p53, FR901228 did induce p21(WAF1/CIP1)in a p53-independent manner.
      Cell clones lacking p21 were not arrested in G1 phase, but continued DNA
      synthesis and were arrested in G2/M phase following FR901228 treatment. Finally,
      FR901228 blunted ERK-2/MAPK activation by EGF whereas early signal transduction
      events remained intact since overall cellular tyrosine phosphorylation after EGF
      stimulation was unaffected. Thus, FR901228, while not directly inhibiting kinase
      activity, causes cyclin D1 downregulation and a p53-independent p21 induction,
      leading to inhibition of CDK and dephosphorylation of Rb resulting in growth
      arrest in the early G1 phase. In contrast to the G1 arrest, the G2/M arrest is
      p21-independent, but is associated with significant cytotoxicity.

PMID- 10952789
TI  - Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis
      in malignant glioma.
AB  - Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective
      outside the central nervous system when compared to the effects obtained when the
      same tumour is located intracerebrally. Recently published studies suggest that
      reduced activity of NK cells in tumour tissue can be increased by histamine. The
      present study was designed to determine whether IL-2 and histamine, alone or in
      combination, can induce anti-tumour effects in an orthotopic rat glioma model.
      One group of rats was treated with histamine alone (4 mg kg(-1)s.c. as daily
      injections from day 6 after intracranial tumour implantation), another group with
      IL-2 alone as a continuous subcutaneous infusion and a third group with both
      histamine and IL-2. The animals were sacrificed at day 24 after tumour
      implantation. IL-2 and histamine in combination significantly reduced tumour
      growth. The microvessel density was significantly reduced, an effect mainly
      affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA
      expression was evident and no significant changes in apoptosis were observed.
      Neither IL-2 nor histamine alone caused any detectable effects on tumour growth.
      Histamine caused an early and pronounced decline in tumour blood flow compared to
      normal brain. The results indicate that the novel combination of IL-2 and
      histamine can be of value in reducing intracerebral tumour growth and, thus, it
      might be of interest to re-evaluate the therapeutic potential of biotherapy in
      malignant glioma.

PMID- 10952790
TI  - Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell
      line.
AB  - Mutation of c-K-ras oncogene is an important step in progression of colon cancer.
      We used a hammerhead ribozyme (KrasRz) against mutated K-ras gene transcripts
      (codon 12, GTT) to inactivate mutant K-ras function in the colon cancer cell line
      SW480, harbouring a mutant K-ras gene. The beta-actin promoter-driven KrasRz
      sequence (pHbeta/KrasRz) was introduced into these cells (SW480/KrasRz), and we
      evaluated its effects on growth of the colon cancer. The gene expression of
      angiogenesis-related molecules (vascular endothelial growth factor and
      thrombospondin) was also estimated in SW480/KrasRz. KrasRz specifically and
      efficiently cleaved the mutant K-ras mRNA but not wild-type mRNA in vitro.
      SW480/KrasRz showed decreased growth rate under tissue culture conditions (P<
      0.01, Dunnett's test). The xenotransplantability of SW480/KrasRz (XeSW480/KrasRz)
      was significantly decreased in nude mice (P< 0.05, Fisher's exact test). Tumour
      volume of the xenografts XeSW480/KrasRz was significantly smaller than that of
      XeSW480/DisKrasRz (P< 0.01, Dunnett's test). Gene expression of VEGF was
      suppressed in SW480/KrasRz, while TSP1 gene expression was enhanced. The
      SW480/KrasRz cells showed apoptosis-related features including nuclear
      condensation and DNA fragmentation. These results suggested that the hammerhead
      ribozyme-mediated inactivation of the mutated K-ras mRNA induced growth
      suppression, apoptosis and alteration of angiogenic factor expression.

PMID- 10952791
TI  - Defining tolerance to enteral feeding in the intensive care unit.

PMID- 10952792
TI  - Metabolic bone disease associated with total parenteral nutrition.

PMID- 10952793
TI  - The paracetamol absorption test: a useful addition to the enteral nutrition
      algorithm?
AB  - BACKGROUND: Enteral nutrition in critically ill patients given via the
      nasogastric route is often decreased or stopped because of large gastric residual
      volumes. AIM: To assess the effect of continuing enteral nutrition in patients
      with an elevated gastric residual volume but normal gastric emptying by the
      paracetamol absorption test. METHODS: The paracetamol absorption test was
      performed on all patients receiving enteral nutrition via a nasogastric tube who
      had a residual volume (assessed every 8 hours) of >150 ml or more than twice the
      hourly infusion rate. Patients were then divided into 2 groups according to the
      result of the test: Group 1 (n=8), normal gastric emptying; and Group II (n=24),
      abnormal gastric emptying. Group I continued to receive enteral nutrition. In
      Group II feeding was interrupted in 18 patients and prokinetic agents
      administered, while a subgroup of six patients continued to receive enteral
      nutrition without prokinetic agents. All patients were followed for evidence of
      delayed gastric emptying and aspiration. RESULTS: Residual volumes were similarly
      elevated in both groups (p=0.25). Enteral nutrition was continued in Group I with
      no adverse effects. Prokinetic agents allowed enteral nutrition to be resumed in
      88% of the 18 Group II patients. Enteral nutrition in the subgroup had to be
      stopped because of persistently elevated residual volumes. CONCLUSION: The
      paracetamol absorption test may be normal in patients with relatively high
      gastric residual volumes. These patients may continue to receive enteral
      nutrition.

PMID- 10952794
TI  - Complications and cost associated with parenteral nutrition delivered to
      hospitalized patients through either subclavian or peripherally-inserted central
      catheters.
AB  - BACKGROUND AND AIMS: Total parenteral nutrition (TPN) is typically delivered
      through catheters inserted into the superior vena cava (SVC) via a subclavian or
      internal jugular vein approach. A peripherally-inserted central venous catheter
      (PICC), utilizing a cephalic or basilic venous approach, may provide a safe
      alternative to the standard catheter approach and, because non-physician
      providers can insert the PICC, may introduce a potential cost-savings to health
      care institutions. We sought to determine if PICC lines are safer and more cost
      effective than the standard central venous catheter approach for hospitalized
      patients who require TPN. METHODS: One hundred and two hospitalized patients (age
      range, 18-88 years) who required TPN were prospectively randomized to receive
      therapy via a centrally-inserted subclavian catheter (n=51) or a peripherally
      inserted PICC line (n=51). The primary end-point was the development of a
      complication requiring catheter removal. Other end-points included catheter
      infection and thrombophlebitis. Cost associated with insertion and maintenance of
      each catheter was also studied. RESULTS: Complication-free delivery rate (without
      the need to remove or replace the catheter) was 67% for subclavian catheters and
      46% for PICC lines (P<0.05). The overall infection rate was 4.9 per 1000 catheter
      days and was similar for each catheter type (P=0.68). PICC lines were associated
      with higher rates of clinically-evident thrombophlebitis (P<0.01), difficult
      insertion attempts (P<0.05), and malposition on insertion (P<0.05). No catheter
      complications resulted in significant long-term morbity or mortality. No
      significant difference was noted between the two catheter types in terms of
      aborted insertion attempts (P=0.18), dislodgement (P=0.12), or line occlusion
      (P=0.25). After standardizing costs for each hospital, the direct institutional
      costs for insertion and maintenance of PICC lines (US$22.32+/-2.74 per day) was
      greater than that for subclavian lines (US$16.20+/-2.96 per day;P<0.05).
      CONCLUSION: PICC catheters have higher thrombophlebitis rates and are more
      difficult to insert into certain patients when compared to the standard
      subclavian approach for central venous access in hospitalized patients who
      require TPN. Because of this, PICCs may be less cost-effective than currently
      believed because of the difficulty in inserting and maintaining the catheter.

PMID- 10952795
TI  - Economic investigation of the use of three-compartment total parenteral nutrition
      bag: prospective randomized unblinded controlled study.
AB  - Optimal strategy for total parenteral nutrition (TPN) administration is essential
      both in terms of clinical effectiveness and economic efficiency. The aim of the
      present economic analysis was to provide a systematic and comprehensive cost
      comparison of the application of three currently available TPN systems: Separate
      Bottles (SB), Hospital-Compounded Bags (HCB) and Three-Compartment Bags (TCB).
      Sixty patients, admitted to the Geneva University Hospital and requiring TPN,
      were randomly assigned to one of the three systems. Three standard TPN formulas
      were prescribed to meet the patients' protein energy needs. TPN-related
      activities of medical, nursing and pharmacy staff were timed for the 24 hours of
      TPN administration. Manpower, nutrient solutions and medical supplies costs were
      calculated on the basis of mean Swiss salaries and hospital prices. TCB was the
      least expensive TPN system. SB and HCB systems' application costs were 120 and
      150% of TCB cost, respectively. All intersystems cost comparisons were
      statistically significant (ANOVA p < or = 0.01). SB system required more items
      and manipulations, resulting in higher nurses manpower cost. Pharmacy overhead
      cost due to compounding was responsible for the higher cost of HCB system.
      Detailed manpower data presented in this study allow for an estimation of TPN
      application costs in other hospitals, using local salaries, specific product
      prices and compounding costs.

PMID- 10952796
TI  - Comparison of the efficacy of medium chain triglycerides with long chain
      triglycerides in total parenteral nutrition in patients with hematologic
      malignancies undergoing peripheral blood stem cell transplantation.
AB  - BACKGROUND AND AIMS: The purpose of this randomized study was to compare the
      efficacy of medium chain triglycerides (MCT) plus long chain triglycerides (LCT)
      with LCT alone in total parenteral nutrition (TPN) solutions in patients with
      various hematologic malignancies who underwent a hematopoietic peripheral blood
      stem cell (PBSC) transplantation. METHODS: Of 36 patients entering into this
      study, 18 received MCT + LCT (group I) and the remaining 18 received LCT alone
      (group II) in TPN solutions. Patients were comparable regarding age, gender,
      donor-recipient gender, diagnosis, body weights, blood group differences and
      number of infused CD34(+) cells/kg. Post - transplant parameters such as duration
      of platelet and neutrophil engraftment, coagulation parameters, number of days of
      febrile neutropenia and antibiotic administration, plasma glucose, triglyceride,
      cholesterol and albumin levels, graft-versus-host disease (GVHD) and first 100
      day mortality were compared in both groups. RESULTS: Median days of neutrophil
      >0.5 x 10(9)/l and platelet of >20 x 10(9)/l in group I and group II were 15
      (range, 8-21), 11 (10-29) and 14 (range, 9-31), 13 (9-18) respectively (P>0.05).
      Median days of febrile neutropenia in group I and II were 10 (range, 4-23) and 7
      (2-13) respectively (P=0.01). Median days of antibiotic administration in group I
      and II were 12 (range, 6-22) and 8 (4-25) respectively (P=0.04). Pre, peri- and
      post-transplant coagulation parameters such as PT, aPTT, and fibrinogen did not
      differ significantly between two groups (P>0.05), as well as plasma glucose,
      triglyceride, cholesterol, albumin levels, GVHD and first 100 day mortality.
      CONCLUSION: There was no difference between patients receiving MCT + LCT (group
      I) and LCT alone (group II) in TPN solutions regarding duration of engraftment
      and coagulation parameters, but numbers of median days of febrile neutropenia and
      days of antibiotic administration were significantly shorter in patients
      receiving LCT alone (group II) than those receiving MCT + LCT (P<0.01 and 0.04
      respectively).

PMID- 10952797
TI  - Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose
      tolerance in healthy young male volunteers with different descarboxy prothrombin
      levels.
AB  - To clarify the roles of vitamin K (VK) in the pancreas, twice oral, glucose
      tolerance tests were examined in 12 healthy young male volunteers before and
      after 1 week of VK tablet intake. Blood were collected by venipucture at 0, 30
      and 120 min after 75 g oral glucose loading. They then took VK tablets (90 mg/d
      of menaquinone-4) for 1 week, and the second glucose tolerance test was examined.
      The subjects were divided into three groups by serum descarboxy prothrombin (DP)
      levels; four of lowest DP (L-DP), middle of DP (M-DP) and highest DP (H-DP)
      levels. They were compared by one-factor analysis of variance and Scheffe's F
      (group differences) and paired t -test (the effects of 1 week of VK intake). Age,
      body mass index and glucose status [plasma glucose (PG) and immunoreactive
      insulin (IRI), hemoglobin-Alc, fructosamine] of all groups were almost the same,
      but the IRI of the H-DP group was higher than that of the other groups at 120 min
      after the glucose loading (mean+/-SEM; L; 10.6+/-0.9, M-; 17.5+/-4.2, H-; 40.4+/
      6.0 microU/ml). One week of VK intake tended to decrease the plasma DP levels of
      all groups and significantly reduced IRI of the H-DP at 120 min by half (before;
      40.4+/-6.0 vs after: 18.4+/-4.6 microU/ml). The IRI/pG ratio in areas under the
      curve (AUC) of H-DP from 0 to 120 min after the loading was significantly
      decreased by 1 week of VK tablet intake (before: 31.0+/-7.4 vs after: 20/1+/-3.8
      microU/g). These results suggested that there may be some relationship between
      pharmacological dose of vitamin K and insulin response.

PMID- 10952798
TI  - Influence of enteral diets supplemented with key nutrients on lymphocyte
      subpopulations in Peyer's patches of endotoxin-boostered mice.
AB  - BACKGROUND AND AIMS: This study was undertaken to compare the effect of different
      key nutrients on lymphocyte subsets of Peyer's patches (PP) and spleen in
      endotoxemic mice. METHODS: Female Balb/c mice were fed over a period of 10 days
      either with an isocaloric and isonitrogenous control diet (Control), a glutamine
      enriched diet (Diet I) or a diet containing glutamine, arginine, glycine, and n-3
      fatty acids (Diet II). On day 7 the mice were challenged intraperitoneally with
      25 microg LPS. The lymphocyte subpopulations (B cells, T cells, CD4+ and CD8+) of
      PP and spleen were analysed by flow cytometry. Glutathione content of small
      intestinal mucosa and spleen was determined by HPLC and luminal small intestinal
      IgA by ELISA. RESULTS: Both experimental diets increased the number of B and T
      cells in the PP and that of T cells in the spleen (P<0.01). Glutathione content
      in PP and spleen was higher under administration of key nutrients (P<0.05). Diet
      II reduced luminal small intestinal IgA content in comparison to the two other
      groups. CONCLUSION: The addition of arginine, glycine and n-3 fatty acids to a
      glutamine supplemented diet does not enhance lymphocyte numbers in PP and spleen,
      but reduces intestinal IgA content.

PMID- 10952799
TI  - Serum fatty acid imbalance in bone loss: example with periodontal disease.
AB  - Among the numerous factors of bone remodelling, the local action of arachidonic
      acid metabolites together with cytokines, is particularly important, especially
      that of prostaglandin PGE2. It has been suggested that the alveolar bone
      destruction in periodontal disease and osteoporosis can be treated by reducing
      the ratio of arachidonic acid in phospholipids, which would diminish
      prostaglandin production. The aim of this study was to evaluate the main serum
      polyunsaturated fatty acids and a possible alteration in the level of arachidonic
      acid in patients suffering from periodontal bone loss. Of the 105 patients who
      participated the study, 78 were suffering from periodontal bone loss and 27
      served as a control group. The fatty acids were measured in serum by gas
      chromatography. The results showed that the level of fatty acids of the n-6
      pathway was higher in our patients with bone loss than in the control group,
      whereas the reverse was observed with fatty acids of the n-3 pathway. In
      conclusion, our patients' bone losses are linked with an imbalance between n-6
      and n-3 fatty acids, which seems to justify a diet increase in 20- and 22-carbon
      fatty acids.

PMID- 10952800
TI  - Complications and long-term outcome of 80 oncology patients undergoing needle
      catheter jejunostomy placement for early postoperative enteral feeding.
AB  - Some findings suggest that needle catheter jejunostomy (NCJ) is associated with a
      significant rate of potentially dangerous complications. The purpose of this
      study was to prospectively evaluate the rate and type of early and late
      complications associated with NCJ in patients with surgical treatment of upper
      gastrointestinal malignancy. Eighty patients underwent NCJ implant at the end of
      their scheduled surgical procedure. Enteral nutrition programme was started on
      postoperative day 1 in the surgical ICU. NCJ was always removed in the outpatient
      clinic after hospital discharge. One case of tube blockage has been observed as
      single short-term complication in this series. No long-term complications have
      been detected after a mean follow-up of 12 months. Routine use of NCJ in
      malnourished patients undergoing major surgical procedures on upper
      gastrointestinal tract is safe and effective.

PMID- 10952801
TI  - Expert working group report on nutrition in adult patients with renal
      insufficiency (Part 2 of 2).

PMID- 10952802
TI  - Drug treatment of non-variceal upper gastrointestinal bleeding.
AB  - Despite many clinical investigations, proof is lacking that pharmacological
      treatments significantly influence the outcome in non-variceal upper
      gastrointestinal bleeding. Reaching conclusions has been hindered by the small
      size of many studies in a situation in which a large number of patients must be
      included if confident conclusions are to be reached. In addition, many studies,
      by comparing two potentially active treatments without a placebo group, have been
      unable to determine whether an equivalence of the active treatments represents
      equivalent but active or equivalent but inactive therapy.

PMID- 10952803
TI  - Drug treatment for bleeding oesophageal varices.
AB  - At the time of diagnosis of cirrhosis, varices are present in about 60% of
      decompensated and 30% of compensated patients. The risk factors for the first
      episode of variceal bleeding in cirrhotic patients are the severity of liver
      dysfunction, a large size of the varices and the presence of endoscopic red
      colour signs, but only a third of patients who suffer variceal haemorrhage
      demonstrate the above risk factors. The only treatment that does not require
      sophisticated equipment or the skills of a specialist, and is immediately
      available, is vasoactive drug therapy. Hence, drug therapy should be considered
      to be the initial treatment of choice and can be administered while the patient
      is transferred to hospital, as has been done in one recent study. Moreover, drug
      therapy is no longer considered to be only a 'stop-gap' therapy until definitive
      endoscopic therapy is performed. Several recent trials have reported an efficacy
      similar to that of emergency sclerotherapy in the control of variceal bleeding.
      Furthermore, recent evidence suggests that those patients with high variceal or
      portal pressure are likely to continue to bleed or re-bleed early, implying that
      prolonged therapy lowering the portal pressure over several days may be the
      optimal treatment. Pharmacological treatment with beta-blockers is safe,
      effective and the standard long-term treatment for the prevention of recurrence
      of variceal bleeding. The combination of beta-blockers with isosorbide-5
      mononitrate needs further testing in randomized controlled trials. The use of
      haemodynamic targets for the reduction of the HVPG response needs further study,
      and surrogate markers of the pressure response need evaluation. Ligation has
      recently been compared with beta-blockers for primary prophylaxis, but there is
      as yet no good evidence to recommend banding for primary prophylaxis if beta
      blockers can be given.

PMID- 10952804
TI  - Current status of endoscopic therapy for ulcer bleeding.
AB  - This article provides an overview of the therapeutic endoscopic modalities
      available for the treatment of peptic ulcer bleeding. The benefits of endoscopic
      haemostasis have been fully demonstrated by three meta-analyses, which included
      most of the controlled trials published until 1992. In this review, an emphasis
      is placed on randomized, prospective comparative trials published during the past
      20 years. Using an evidence-based medicine approach, the results of meta-analyses
      are translated into efficacy measures known as relative and absolute risk
      reductions, and number needed to treat. Single-modality treatments with injection
      agents such as epinephrine, sclerosants and thrombogenic substances, or with
      thermal therapies, are efficacious and comparable. Combination therapy involving
      injection and thermal techniques may offer an advantage over single-method
      therapy. The differences in the results between clinical trials and routine
      clinical practice, and among the various randomized studies, are probably related
      to operators' experience and variations in technique rather than to inconsistency
      of endoscopic haemostasis.

PMID- 10952805
TI  - Value of stigmata in decision-making in gastrointestinal haemorrhage.
AB  - The stigmata of recent haemorrhage are endoscopically identified features that
      have a predictive value for the risk of further bleeding and thus help to
      determine which patients should receive endoscopic therapy. In conjunction with
      endoscopic features, clinical features related to the magnitude of bleeding and
      to patient co-morbidity have important independent effects on the risk of further
      haemorrhage. Stigmata have been best studied in the context of bleeding ulcers,
      the most common cause of upper gastrointestinal bleeding. Stigmata in ulcers are
      usually classified as active bleeding (spurting or oozing), a non-bleeding
      visible vessel, an adherent clot, a flat pigmented spot, or a clean base, in
      order of decreasing risk of further haemorrhage. Ulcer size and location may also
      affect the re-bleeding potential. Recent data suggest that both non-pigmented
      visible vessels and adherent clots have a higher risk of re-bleeding than was
      previously thought. The wide variation in prevalence and re-bleeding rates
      reported for various stigmata in the literature probably reflects variations in
      the definitions of stigmata and of re-bleeding, the vigour with which the ulcer
      bases are washed, the co-morbidity and ages of the patients, and the severity of
      bleeding encountered. Inter-observer agreement in the classification of stigmata
      is relatively poor and limits the utility of endoscopic features alone in making
      decisions regarding the management of patients with bleeding peptic ulcers.
      Imaging devices such as Doppler probes are being evaluated to refine the
      identification of underlying vessels and their re-bleeding potential, but the
      utility of these is currently uncertain. The findings of low-risk endoscopic
      stigmata in a haemodynamically and otherwise stable patient can in many cases
      allow out-patient management.

PMID- 10952806
TI  - Injection therapy for endoscopic haemostasis.
AB  - Endoscopic injection is widely used for the arrest of active ulcer bleeding and
      for prevention of re-bleeding from ulcers with visible vessels. Although of
      proven value in clinical trials, mechanisms of action are unclear; tamponade,
      vasoconstriction, endarteritis and a direct effect upon the clotting process at
      the site of the arterial defect have been proposed. Clinical trials show that
      dilute adrenaline is an effective agent and that the addition of sclerosants or
      alcohol confirms no extra benefit, yet risks serious side-effects. The best
      results are associated with injection of fibrin glue or thrombin which stimulate
      formation of a stable blood clot. The efficacy of injection, thermal modalities
      such as the heater probe and electrocoagulation using BICAP are comparable. In
      general, there is an advantage in combining injection with a thermal modality,
      although this may have merit in patients with severe, active ulcer bleeding.
      Patients who re-bleed following successful primary haemostatic injection
      treatment can be considered for further endoscopic intervention, but the decision
      to undertake a surgical operation or repeat endoscopic therapy is a matter of
      clinical judgement.

PMID- 10952807
TI  - Thermal probes alone or with epinephrine for the endoscopic haemostasis of ulcer
      haemorrhage.
AB  - In the last two decades, significant progress has been made in the diagnosis,
      prognostication and treatment of patients with severe peptic ulcer haemorrhage.
      Patients can now be risk stratified by clinical presentation and endoscopic
      stigmata of ulcer haemorrhage. The purposes of this chapter are to discuss: (1)
      the techniques of thermal probe with or without epinephrine for haemostasis of
      ulcers with major stigmata of haemorrhage and (2) the outcomes of treatment of
      patients with ulcer haemorrhage treated with endoscopic thermal probes or other
      therapies, medical therapy and/or surgery. Compared to medical therapy alone,
      patients with major stigmata actively bleeding ulcers, non-bleeding visible
      vessels and non-bleeding adherent clots have been shown to benefit from
      endoscopic haemostasis with bipolar probe, heater probe, lasers or epinephrine
      injection. Outcomes showing significant improvement include blood transfusions,
      emergency surgery rates and length of hospital stay. Meta-analyses have also
      reported improvements in mortality for endoscopic compared with medical therapy
      of patients with severe ulcer haemorrhage and major stigmata. Patients with minor
      stigmata of ulcer haemorrhage (such as flat spots) or no stigmata (clean-based
      ulcers) do not benefit from endoscopic haemostasis. Thermal probes have the
      advantages of good coaptive coagulation, target irrigation, portability and
      relative inexpense. Recently, patients with active arterial bleeding, non
      bleeding adherent clots or non-bleeding visible vessels have been reported to
      have better results with combination epinephrine injection and thermal probe
      compared to monotherapy alone (such as injection, bipolar or heater probe). In
      addition, repeat endoscopic combination therapy has been reported to be as
      effective but safer than emergency surgery for management of recurrent ulcer
      haemorrhage.

PMID- 10952808
TI  - Combination therapies for the endoscopic treatment of gastrointestinal bleeding.
AB  - This review discusses the background and analysis of data in the literature
      regarding the effect of a combination of endoscopic therapies on the treatment of
      bleeding gastroduodenal ulcers. Although these techniques are commonly used,
      convincing data to support combinations of injection therapies are scarce, and
      various studies give somewhat conflicting results. In one study, a combination of
      the injection of adrenaline and a high dose of thrombin was superior to using
      adrenaline alone. The combination of injection therapy with a thermal method
      tends to give better results than injection therapy alone in several studies, but
      the difference is only statistically significant in one study (which uses the
      gold probe). The data regarding a combination of injection therapy with
      haemostatic clips are somewhat discordant regarding the effect of the haemoclip
      itself, but none of the studies found an advantage of combining the two
      modalities. Some studies suggest that subgroups may exist, such as ulcers with
      spurting haemorrhage, in which combined treatment might be more useful.

PMID- 10952809
TI  - Mechanical endoscopic methods of haemostasis for bleeding peptic ulcers: a
      review.
AB  - Re-bleeding following endoscopic therapy for gastrointestinal bleeding remains
      common probably because injection and thermal methods for treating bleeding are
      of limited efficacy, especially in the presence of a large bleeding artery. This
      chapter reviews mechanical methods of endoscopic haemostasis. The design of
      clips, which can be delivered through flexible endoscopes, is reviewed with
      experimental and clinical data of their efficacy. The need for improvements in
      clip design is stressed. Experimental studies and preliminary clinical data where
      available on a variety of other mechanical methods of haemostasis are presented,
      including band ligation, endoloops, sewing machines, stapling machines, ulcer
      clamps, corkscrews, balloon tamponade and ferromagnetic tamponade. New, less
      invasive, surgical methods which might have a place in ulcer haemostasis,
      including transgastric endoluminal surgery and flexible endoscopic ulcer excision
      with wound closure, are discussed. Mechanical methods offer the best prospect for
      improvements in security of endoscopic haemostasis for bleeding peptic ulcer.
      More development is required if the results are to improve.

PMID- 10952810
TI  - The role of endoscopic therapy in the treatment of bleeding varices.
AB  - The role of endoscopy in bleeding varices is both diagnostic and therapeutic.
      While sclerotherapy of oesophageal varices remains an established modality,
      ligation has, in view of its higher safety margin, turned out to be superior in
      recent years. The excellent initial results of ligation are, however, tainted by
      a higher recurrence rate in the long term. Since the end-point of treatment is
      the achievement and maintenance of variceal eradication, the addition of low-dose
      sclerotherapy following initial eradication by ligation seems to be the optimal
      method to combine the best of both techniques. In the management of life
      threatening bleeding from oesophageal varices and gastric varices, cyanoacrylate
      remains the only promising non-surgical option. Primary endoscopic prophylaxis is
      still under evaluation. It is only justified in high-risk patients with large
      varices bearing red colour signs and in the presence of an intolerance of or
      contra-indication to propranolol. When indicated, ligation seems to be
      preferable, and the addition of low-dose sclerotherapy after initial variceal
      eradication may maintain the benefits accrued in such high-risk patients. The
      present review examines the available evidence regarding the above issues in the
      recent literature.

PMID- 10952811
TI  - The role of Doppler ultrasound in gastrointestinal bleeding.
AB  - The management of acute gastrointestinal bleeding is the domain of endoscopy.
      More than half of all episodes of upper gastrointestinal bleeding are attributed
      to bleeding peptic ulcers, and it is important to assess the risk of recurrent
      bleeding and to determine the appropriate treatment. However, the visual
      assessment of lesions (Forrest classification) is not always accurate and shows
      high interobserver variability (especially for visible vessels at the ulcer base,
      associated with a high rate of re-bleeding). Doppler ultrasound was thus
      introduced, and several studies have demonstrated that, with Doppler examination,
      these vessels can be identified. Doppler ultrasound is also used to monitor the
      effects of endoscopic therapy. In a prospective randomized trial, Doppler
      ultrasound proved superior to the Forrest classification. Treatment based on this
      technique resulted in significantly lower rates of re-bleeding and mortality. The
      Doppler classification may be able to contribute to a safer and more cost
      effective management of patients with acute peptic ulcer bleeding.

PMID- 10952813
TI  - Index

PMID- 10952815
TI  - Anniversary editorials

PMID- 10952812
TI  - Surgery in the acute management of bleeding peptic ulcer.
AB  - The management of bleeding peptic ulcers is an increasing challenge in an ageing
      population. Endoscopic therapy reduces the need for emergency surgery in bleeding
      peptic ulcers, and ulcers that fail endoscopic therapy are often 'difficult'
      ulcers, highly demanding for most gastric surgeons. Mortality in patients
      requiring eventual salvage surgery is high. Planned urgent surgery is preferable
      to emergency surgery in elderly patients. Initial endoscopic control offers an
      opportunity for selecting high-risk ulcers for early surgery. Such a logical
      approach has, however, not been supported by evidence in the literature. At
      surgery, an aggressive approach is recommended. Post-operative bleeding is more
      common after lesser surgery, and this complication is often fatal. When re
      bleeding occurs, a selective approach is suggested as emergency surgery carries
      with it a substantial mortality. Large chronic ulcers with exigent bleeding are
      less likely to respond to endoscopic re-treatment. Expedient surgery is advised
      for these patients.

PMID- 10952816
TI  - The forgotten past: the practice of cardiology in the 1950s and now.

PMID- 10952817
TI  - Seeing the heart; the success story of cardiac imaging.

PMID- 10952818
TI  - Improving the quality and dissemination of guidelines: the quest for the Holy
      Grail.

PMID- 10952819
TI  - Predicting the outcome of revascularization in ischaemic left ventricular
      dysfunction.

PMID- 10952820
TI  - Heart failure and glucose abnormalities: an increasing combination with poor
      functional capacity and outcome.

PMID- 10952821
TI  - Different imaging approaches in the assessment of left ventricular dysfunction:
      all things equal?

PMID- 10952822
TI  - Mitral flow derived Doppler indices of left ventricular diastolic function.

PMID- 10952823
TI  - Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on
      Pulmonary Embolism, European Society of Cardiology.

PMID- 10952824
TI  - Regional myocardial function--a new approach.

PMID- 10952825
TI  - Sensitivity, specificity, and predictive accuracies of non-invasive tests, singly
      and in combination, for diagnosis of hibernating myocardium.
AB  - OBJECTIVE: To determine the best test(s) for predicting functional recovery of
      hibernating myocardium after reperfusion. METHODS: A prospective study to compare
      echocardiographic left ventricular diastolic wall thickness (> or =5 mm), low
      dose dobutamine echocardiography and rest-redistribution thallium-201
      scintigraphy, alone and in combination, for predicting recovery of left
      ventricular akinesis after surgical revascularization. RESULTS: Twenty-eight
      consecutive patients aged 58+/-9 years were studied. Of the 448 left ventricular
      segments, 263 were akinetic at rest; 230/263 (87%) had wall thickness > or =5 mm,
      135 (51%) had a positive response and 175 (66.5%) were graded viable on thallium.
      Of akinetic segments 61% improved after surgery. Left ventricular score decreased
      from 2.3+/-0.4 to 1.8+/-0.4 (P<0.01) and ejection fraction increased from 27+/-10
      to 37+/-14% (P<0.01). For predicting results at 1 year, diastolic wall thickness
      had a sensitivity and a predictive accuracy of a negative test of 100% but a
      specificity of 28% and predictive accuracy of a positive test of 61%. The
      addition of dobutamine echocardiography or thallium-201 improved the predictive
      accuracy of a positive test to 76% and 69%, respectively; the addition of both
      tests was not of greater benefit than that of a single test. CONCLUSIONS:
      Diastolic wall thickness <5 mm on echocardiography was the best simple and single
      predictor of non-recovery of left ventricular dysfunction. The addition of
      dobutamine echocardiography or thallium-201, but not both, was the best solution
      for predicting recovery of left ventricular dysfunction. In times of limited
      resources, these findings are important from a clinical point of view.

PMID- 10952826
TI  - Glucose and insulin abnormalities relate to functional capacity in patients with
      congestive heart failure.
AB  - AIMS: In addition to diabetes mellitus, less severe abnormalities of glucose and
      insulin metabolism may be related to functional status in patients with heart
      failure. We examined the relationship of hyperglycaemia (> or =6.1 mmol. l(-1))
      and hyperinsulinaemia (> or =11.2 mU. l(-1)) to functional status and cardiac
      function in patients with heart failure. METHODS AND RESULTS: Fasting plasma
      glucose and insulin levels were obtained in 663 heart failure patients. The
      average left ventricular ejection fraction was 0.28+/-0.07, 63% were in New York
      Heart Association Functional Class (NYHA-FC) I/II and 37% were in NYHA-FC III/IV.
      Twenty seven percent had diabetes mellitus, but an additional 8% had undiagnosed
      diabetes mellitus (glucose > or =7 mmol. l(-1)) and 9% had glucose levels between
      6.1 and 7 mmol. l(-1), so that a total of 43% (287) of patients had elevated
      glucose levels (> or =6.1 mmol. l(-1)). In general, more diabetic patients had
      NYHA-FC III/IV symptoms, shorter 6 min walk distances, but similar left
      ventricular ejection fractions compared to non-diabetic patients. The non
      diabetic patients in NYHA-FC III/IV had higher glucose and insulin levels than
      patients in NYHA-FC I/II (6.3+/-0.2 vs 5.6+/-0.1 mmol. l(-1), P<0.001 and 19.6+/
      2.3 vs 10. 2+/-0.6 mU. l(-1), P<0.001). Non-diabetic patients with elevated
      glucose levels had shorter 6 min walk distances compared to those with normal
      glucose levels (368.2+/-8 m vs 389.+/-4 m, P=0.02), however, left ventricular
      ejection fraction was similar. CONCLUSION: Glucose abnormalities are extremely
      common in heart failure patients (43% of patients). Diabetes mellitus and
      hyperglycaemia or hyperlinsulinaemia in non-diabetic patients were related to
      worse symptomatic status but not worsening left ventricular ejection fraction
      compared to patients with normal glucose and insulin levels.

PMID- 10952827
TI  - Mitral flow derived Doppler indices of left ventricular diastolic function in a
      general population; the Tromso study.
AB  - AIMS: Left ventricular diastolic dysfunction has been proposed as the basis of
      heart failure in patients with normal left ventricular systolic function. Doppler
      indices of mitral inflow have been widely used to diagnose this condition and
      have been shown to correlate well with increased left atrial pressure in patients
      with cardiovascular disease. We wanted to establish age-specific criteria for
      normality of these indices in a large population and to determine the association
      of abnormal values to age and cardiovascular disease. METHODS AND RESULTS: In our
      sample of subjects aged 25-85 years, 3022 had pulsed Doppler measurements of
      mitral inflow velocities and early inflow deceleration time. The association of
      these indices to age and gender were established in a 'healthy' reference
      subsample of 949 subjects. Age-specific percentiles showed a significant decline
      with increasing age for peak early mitral inflow velocity and the ratio of peak
      early and atrial inflow velocities (E/A ratio), whereas early inflow deceleration
      time and peak atrial inflow velocity showed a significant increase with
      increasing age. According to current criteria for diastolic dysfunction, the
      prevalence of dysfunction decreases with increasing age in the general
      population, as well as in the subgroup with cardiovascular disease. Only 7% of
      the variance in deceleration time was explained by cardiovascular disease or risk
      factors. For the E/A ratio, however, 41 and 48% of the variance were explained
      for men and women, respectively. CONCLUSION: Age- and gender-specific criteria
      for normality are provided. Our data confirm the existence of a significant
      effect of age and gender on mitral Doppler indices of diastolic dysfunction.
      However, Doppler criteria for diastolic dysfunction based on these measurements
      need revision.

PMID- 10952828
TI  - Comparison of left ventricular ejection fraction and volumes in heart failure by
      echocardiography, radionuclide ventriculography and cardiovascular magnetic
      resonance; are they interchangeable?
AB  - AIMS: To prospectively compare the agreement of left ventricular volumes and
      ejection fraction by M-mode echocardiography (echo), 2D echo, radionuclide
      ventriculography and cardiovascular magnetic resonance performed in patients with
      chronic stable heart failure. It is important to know whether the results of each
      technique are interchangable, and thereby how the results of large studies in
      heart failure utilizing one technique can be applied using another. Some studies
      have compared cardiovascular magnetic resonance with echo or radionuclude
      ventriculography but few contain patients with heart failure and none have
      compared these techniques with the current fast breath-hold acquisition
      cardiovascular magnetic resonance. METHODS AND RESULTS: Fifty two patients with
      chronic stable heart failure taking part in the CHRISTMAS Study, underwent M-mode
      echo, 2D echo, radionuclude ventriculography and cardiovascular magnetic
      resonance within 4 weeks. The scans were analysed independently in blinded
      fashion by a single investigator at three core laboratories. Of the
      echocardiograms, 86% had sufficient image quality to obtain left ventricular
      ejection fraction by M-mode method, but only 69% by 2D Simpson's biplane
      analysis. All 52 patients tolerated the radionuclude ventriculography and
      cardiovascular magnetic resonance, and all these scans were analysable. The mean
      left ventricular ejection fraction by M-mode cube method was 39+/-16% and 29+/
      15% by Teichholz M-mode method. The mean left ventricular ejection fraction by 2D
      echo Simpson's biplane was 31+/-10%, by radionuclude ventriculography was 24+/-9%
      and by cardiovascular magnetic resonance was 30+/-11. All the mean left
      ventricular ejection fractions by each technique were significantly different
      from all other techniques (P<0.001), except for cardiovascular magnetic resonance
      ejection fraction and 2D echo ejection fraction by Simpson's rule (P=0.23). The
      Bland-Altman limits of agreement encompassing four standard deviations was widest
      for both cardiovascular magnetic resonance vs cube M-mode echo and cardiovascular
      magnetic resonance vs Teichholz M-mode echo at 66% each, and was 58% for
      radionuclude ventriculography vs cube M-mode echo, 44% for cardiovascular
      magnetic resonance vs Simpson's 2D echo, 39% for radionuclide ventriculography vs
      Simpson's 2D echo, and smallest at 31% for cardiovascular magnetic resonance
      radionuclide ventriculography. Similarly, the end-diastolic volume and end
      systolic volume by 2D echo and cardiovascular magnetic resonance revealed wide
      limits of agreement (52 ml to 216 ml and 11 ml to 188 ml, respectively).
      CONCLUSION: These results suggest that ejection fraction measurements by various
      techniques are not interchangeable. The conclusions and recommendations of
      research studies in heart failure should therefore be interpreted in the context
      of locally available techniques. In addition, there are very wide variances in
      volumes and ejection fraction between techniques, which are most marked in
      comparisons using echocardiography. This suggests that cardiovascular magnetic
      resonance is the preferred technique for volume and ejection fraction estimation
      in heart failure patients, because of its 3D approach for non-symmetric
      ventricles and superior image quality.

PMID- 10952829
TI  - ESC news and appointments

PMID- 10952830
TI  - Inter-regional differences in acute coronary syndrome trials.

PMID- 10952831
TI  - Are data from clinical registries of any value?

PMID- 10952832
TI  - National and regional registries: what good are they?

PMID- 10952833
TI  - Chest pain and a non-diagnostic ECG: trying not to be frustrated.

PMID- 10952834
TI  - Management of acute coronary syndromes: acute coronary syndromes without
      persistent ST segment elevation; recommendations of the Task Force of the
      European Society of Cardiology.

PMID- 10952835
TI  - Inter-regional differences and outcome in unstable angina; analysis of the
      international ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin in
      Non-Q-wave Coronary Events.
AB  - AIMS: Worldwide there is a large variation in outcome (death, myocardial
      infarction and recurrent myocardial infarction) in patients with unstable angina
      or non-Q wave myocardial infarction. These variations may be explained by
      differences in characteristics of the presenting patients. Here we describe
      differences in patient presentation, treatment protocols and outcome and we
      investigate their relationship using data from the ESSENCE (Efficacy and Safety
      of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trial. METHODS: A total
      of 2981 patients from six countries which enrolled more than 100 patients were
      included in the present analysis: United States, Canada, Argentina, France, the
      Netherlands and United Kingdom. Logistic regression analysis was performed to
      determine the effect of baseline characteristics on regional outcome. RESULTS: At
      day 30, the lowest triple end-point rate, irrespective of study drug treatment,
      was noted in the Netherlands (18.9%) and the highest in Argentina (30.5%). A
      model including the variables age > or = 65 years, prior angina, diabetes, prior
      aspirin use, ECG changes at baseline and diagnosis of non-Q wave myocardial
      infarction and dummy variables for Argentina and France resulted in concordance
      of about 60%. CONCLUSIONS: Inter-regional differences in outcome in unstable
      angina and non-Q wave myocardial infarction patients can reasonably well be
      explained by differences in patient characteristics. However, other so far
      unidentified variables present in Argentina and France also contributed to
      differences in outcome and their effect warrants further investigation.

PMID- 10952836
TI  - The ENACT study: a pan-European survey of acute coronary syndromes. European
      Network for Acute Coronary Treatment.
AB  - AIM: The European Network for Acute Coronary Treatment (ENACT) study was designed
      to collect prospective information across Europe on the relative frequency,
      diagnosis and management of the whole spectrum of acute coronary syndromes.
      METHODS: Cardiologists, who were respondents to mailings sent out to 17 European
      countries with the target of reaching one centre per million inhabitants,
      completed a prospective patient record, each physician providing information on
      10 consecutive patients with a working diagnosis on admission of acute coronary
      syndrome, and a questionnaire. RESULTS: A total of 390 responses were received
      (0.91/10(6)population) with data on 3092 patients in 29 countries. The patient
      population comprised 1431 (46%) with an initial working diagnosis of unstable
      angina/non-ST-segment elevation myocardial infarction, 1205 (39%) with myocardial
      infarction and 445 (14%) with suspected acute coronary syndrome. The ratio of
      unstable angina to myocardial infarction was 1.2:1 and this was similar across
      Europe. An initial diagnosis of myocardial infarction was more likely to be
      confirmed than unstable angina or suspected acute coronary syndrome. There were
      wide variations in the rates of angiography and percutaneous coronary
      intervention across Europe. Most unstable angina patients received aspirin,
      nitrates and heparin (unfractionated heparin 44% intravenous, 16% subcutaneous;
      low-molecular-weight heparin 50%). Overall, 50% of unstable angina patients and
      34% of myocardial infarction patients received low-molecular-weight heparin and
      6% and 8% respectively received a glycoprotein IIb/IIIa inhibitor, but there were
      large inter-country differences. There were also national differences in the use
      of calcium antagonists, angiotensin-converting enzyme inhibitors and beta
      blockers. CONCLUSION: The ENACT study provides robust data, for the first time,
      on the relative frequency of unstable angina and acute myocardial infarction
      across Europe. It provides insight into differences in management across Europe
      and a reference benchmark of current treatment.

PMID- 10952837
TI  - Clinical outcomes, risk stratification and practice patterns of unstable angina
      and myocardial infarction without ST elevation: Prospective Registry of Acute
      Ischaemic Syndromes in the UK (PRAIS-UK)
AB  - AIMS: To determine characteristics, outcomes, prognostic indicators and
      management of patients with acute coronary syndromes without ST elevation.
      METHODS AND RESULTS: A prospective registry was carried out with follow-up for 6
      months after index hospital admission. A history of acute cardiac chest pain was
      required plus ECG changes consistent with myocardial ischaemia and/or prior
      evidence of coronary heart disease. Patients with ST elevation or those receiving
      thrombolytic therapy were excluded. A total of 1046 patients were enrolled from
      56 U.K. hospitals. The mean age was 66+/-12 years and 39% were female. The rate
      of death or non-fatal myocardial infarction at 6 months was 12.2% and of death,
      new myocardial infarction, refractory angina or re-admission for unstable angina
      at 6 months was 30%. In a multivariate analysis, patients >70 years had a
      threefold risk of death or new myocardial infarction compared with those <60
      years (P<0.01) and those with ST depression or bundle branch block on the ECG had
      a five-fold greater risk than those with normal ECG (P<0.001). Aspirin was given
      to 87% and heparin to 72% of patients in hospital. At 6 months 56% received no
      lipid-lowering therapy at all. The 6-month rate of coronary angiography was 27%
      and any revascularization 15%. CONCLUSIONS: In this cohort there was a one in
      eight chance of death or myocardial infarction, and a one in three chance of
      death, new myocardial infarction, refractory angina or re-admission for unstable
      angina, over 6 months. Age and baseline ECG were useful markers of risk. Aspirin,
      heparin and statins were not given to about one-sixth, one-third and one-half
      respectively. Rates of angiography and revascularization appear low. A review of
      treatment strategies of unstable angina and myocardial infarction without ST
      elevation is warranted in the U.K. to ensure that patients are receiving optimum
      treatments to reduce mortality and morbidity.

PMID- 10952839
TI  - The combination of a continuous 12-lead ECG and troponin T; a valuable tool for
      risk stratification during the first 6 hours in patients with chest pain and a
      non-diagnostic ECG.
AB  - AIMS: The aim was to examine the early prognostic value of a combination of a
      continuous 12-lead ECG and troponin T in patients with chest pain and an ECG non
      diagnostic for acute myocardial infarction. METHODS AND RESULTS: ST monitoring
      was performed and samples for analysis of troponin T were collected from
      admission for 12 h from 598 patients. After 6 h, the peak value of troponin T in
      27% was > or = 0.10 microg.l(- 1), while 15% had had ST episodes, defined as
      transient ST deviations of at least 0.1 mV. Both a troponin T > or = 0.10 microg.
      l(-1) and ST episodes predicted worsening outcome. After 30 days, there were 6.8%
      and 1.4% (P<0.01) cardiac deaths or myocardial infarctions in the group with and
      without troponin T > or = 0.10 microg.l(-1), respectively. The corresponding
      event rates in patients with and without ST episodes were 10% and 1.6% (P<0.001).
      In a multivariate analysis both troponin T and ST episodes were independent
      predictors of cardiac death or myocardial infarction. When ST monitoring and
      troponin T status were combined, patients could be divided into low-,
      intermediate-, and high-risk groups. CONCLUSIONS: A combination of continuous 12
      lead monitoring and troponin T seems to be a valuable tool for risk
      stratification during the first 6 h in this population.

PMID- 10952838
TI  - A national Survey of Acute Myocardial Infarction and Ischaemia (SAMII) in the
      U.K.: characteristics, management and in-hospital outcome in women compared to
      men in patients under 70 years.
AB  - AIMS: To assess the clinical characteristics, management and outcome of women
      compared to men with acute myocardial infarction or ischaemia. DESIGN: A
      prospective clinical survey was made in a random sample of 94 District General
      Hospitals in the U.K. 1064 patients, <70 years of age, comprising six consecutive
      females and six consecutive males from each hospital, diagnosed on admission as
      acute coronary syndromes (myocardial infarction or myocardial ischaemia) were
      studied. Outcome measures included: admission and final diagnosis, time to
      delivery of care, inpatient management, complications and clinical outcome.
      RESULTS: Five hundred and three women and 561 men were admitted with a diagnosis
      of acute myocardial infarction or myocardial ischaemia. Women were older, waited
      longer between seeking and receiving advice, and much less likely to have
      infarction than men. After adjustment for age, diagnosis and past medical history
      there were no gender differences in initial and subsequent hospital management,
      in complications (recurrent ischaemia, arrhythmias, temporary pacing, heart
      failure), any routine procedure or outcome. Of all patients, 3.4% died in a
      District General Hospital, 12.2% were transferred to Specialist Cardiac Centres
      and 84.4% discharged home. Prophylactic medication on discharge was similar for
      men and women. CONCLUSION: After adjustment for age, diagnosis and past medical
      history, although women waited longer between seeking and receiving medical
      advice, in hospital their assessment, management, complications, outcome and
      follow-up arrangements were the same as for men. In hospital, management and
      outcomes were mainly influenced by age, diagnosis (infarction or ischaemia), a
      past history of coronary disease, but not by gender. This large, nationally
      representative, survey has found no evidence of important gender difference in
      the hospital management of acute ischaemic syndromes.

PMID- 10952840
TI  - Reactivation of coagulation after stopping infusions of recombinant hirudin and
      unfractionated heparin in unstable angina and myocardial infarction without ST
      elevation: results of a randomized trial. OASIS Pilot Study Investigators.
      Organization to Assess Strategies for Ischemic++ Syndromes.
AB  - AIMS: To compare effects of heparin and hirudin on biochemical markers of
      coagulation. METHODS AND RESULTS: Patients (n=395) with unstable angina or
      myocardial infarction without ST elevation were randomized to a 72-h infusion of
      one of three regimens: unfractionated heparin (bolus of 5000 IU followed by an
      infusion of 1200 IU. h(-1)), low-dose hirudin (HBW 023; 0.2 mg. kg(-1)bolus
      followed by 0.10 mg. kg(-1). h(-1)) or medium-dose hirudin (0.4 mg. kg(-1)bolus
      followed by 0.15 mg. kg(-1). h(-1)). Infusions were adjusted to maintain an
      activated partial thromboplastin time of between 60-100 s. Activated partial
      thromboplastin time, prothrombin fragment 1.2 (F1.2), thrombin antithrombin III
      complex and D-dimer were measured before, during and after the infusion. Median
      activated partial thromboplastin time was similar in the two groups early on, but
      was significantly lower in the heparin group than in the combined hirudin group
      48 h after starting the infusion (53 s and 75 s, respectively;P<0.001), and 6 h
      after stopping (31 s and 46 s, respectively;P<0.001). Median F1.2 levels were not
      significantly different between the groups during the infusion. Median thrombin
      antithrombin III levels in the heparin and hirudin groups were 2.8 microg. l(
      1)and 2.3 microg. l(-1), respectively, at 6 h (P<0.001), and 3.0 microg. l(-1)and
      2.3 microg. l(-1), respectively, at 48 h (P<0.001). Median D-dimer levels were
      320 ng. ml(-1)and 260 ng. ml(-1)48 h after starting the infusion in the heparin
      and hirudin groups, respectively (P<0.001), and 415 ng. ml(-1)and 280 ng. ml(-1),
      respectively (P<0.001) 6 h after stopping. D-dimer levels were significantly
      elevated above baseline values in both groups 24-48 h after stopping the
      infusions. CONCLUSIONS: The greater reduction of thrombin antithrombin III and D
      dimer during the hirudin infusion supports the hypothesis that hirudin is a more
      potent antithrombin agent than heparin. Increased D-dimer levels after stopping
      heparin or hirudin suggest that there is an ongoing pro-coagulant state. These
      results point to the greater efficacy of hirudin in preventing early clinical
      events (death, myocardial infarction and refractory ischaemia) compared with
      heparin that have been observed in large randomized trials. Persistent activation
      of coagulation afterstopping infusions in our study suggests that a longer course
      of antithrombotic treatment may be needed to pacify the thrombus.

PMID- 10952841
TI  - Impact of red wine on antioxidant status in vivo.

PMID- 10952842
TI  - Brugada syndrome and sudden death.

PMID- 10952843
TI  - A reply

PMID- 10952845
TI  - A reply

PMID- 10952844
TI  - Clinical implications of increased plasma angiotensin II concentrations despite
      ACE inhibitor therapy in patients with congestive heart failure: the issue of non
      compliance with therapy.

PMID- 10952846
TI  - The host and the skeletal infection: classification and pathogenesis of acute
      bacterial bone and joint sepsis.
AB  - Bone and joints are normally sterile areas. Bacteria may reach these sites by
      either haematogenous spread or spread from an exogenous or endogenous contiguous
      focus of infection. Bone infection, or osteomyelitis, is characterized by a
      progressive infectious process resulting in inflammatory destruction of bone,
      bone necrosis and new bone formation. Joint infections, or infectious arthritis,
      arise either from the haematogenous spread of organisms through the highly
      vascularized synovial membrane or from direct extension of a contiguous bone or
      soft tissue infection. The most commonly involved joints are the knee and the
      hip, although any joint can become infected. Infectious arthritis is
      monoarticular in 90% of cases. Some of the questions to be answered in this
      chapter include: how bacteria reach and cause damage in the bones and joints;
      what the current classification systems of bone and joint infections are; what
      some risk factors and host factors associated with bone and joint infection are;
      what some current characteristics of musculoskeletal infections are and whether
      the damage to joints can be diminished by treatment.

PMID- 10952848
TI  - Septic arthritis.
AB  - Septic arthritis is a direct invasion of the joints by pathogenic micro
      organisms. These micro-organisms and their products stimulate the release of pro
      inflammatory cytokines and proteolytic enzymes that induce an inflammatory
      response and degradation of the cartilage. Staphylococcus aureus remains the most
      prevalent micro-organism, and the most important aetiological change has been the
      decreased incidence of gonorrhoea, which is related to changes in sexual
      behaviour as a result of the HIV epidemic. Diagnostic suspicion is based on
      clinical symptoms, imaging findings and examination of synovial fluid.
      Scintigraphy and magnetic resonance imaging are useful methods for localizing and
      defining the extent of infection. The definitive diagnosis is based on the
      isolation and culture of the pathogen from synovial fluid. Optimal cultures are
      obtained by inoculating the synovial fluid immediately into blood culture
      bottles. Treatment includes initial empirical antibiotics, which are modified
      according to the synovial fluid culture. It is recommended that 3-4 weeks of
      intravenous antibiotic therapy are followed by 2 or 3 more weeks of an oral
      regimen. Adequate drainage may be performed by means of repeated needle
      aspiration, arthroscopy or surgery. Recent studies on the pathogenic mechanisms
      of septic arthritis have led to the simultaneous use of intra-articular steroids
      and antibiotics in order to reduce articular damage.

PMID- 10952847
TI  - Micro-organisms responsible for osteo-articular infections.
AB  - Identification of the aetiological agents responsible for bone and joint
      infections requires either hard to obtain specimens that are easy to interpret,
      or easy to obtain specimens of difficult interpretation. Isolates obtained by
      blood cultures, arthrocentesis, or trephine or surgical biopsy bone samples are
      usually clinically significant. In contrast, samples obtained from sinus tracts
      or through open wounds are very often easy to obtain but difficult to interpret.
      Micro-organisms such as Staphylococcus epidermidis are the most common cause of
      infections around prosthetic joint materials but are usually of little
      significance when obtained from the sinus tract of a patient with chronic
      osteomyelitis of the tibia without osteosynthesis. Other micro-organisms to be
      interpreted with caution include Corynebacterium spp. and Enterococcus spp. The
      most important families of antimicrobial agents and their utility in bone and
      joint infections are briefly reviewed at the end of the chapter. Bone and joint
      infections require long-term antimicrobial therapy based on the correct diagnosis
      and the appropriate selection of antimicrobial treatment.

PMID- 10952849
TI  - Pyogenic vertebral osteomyelitis/disc infection.
AB  - Spinal osteomyelitis has been known about for centuries. Granulomatous infection
      was the principal offender in the past, but nowadays, with an increased number of
      patients at 'risk', the proportion of pyogenic infections has risen. Awareness of
      this is the essence of early diagnosis. The advent of magnetic resonance imaging
      has proved a major milestone; with its high sensitivity and specificity, it is an
      essential part of the diagnostic work-up. The treatment of spinal osteomyelitis
      follows the same basic principles as for any infection. Once the diagnosis has
      been established, early conservative treatment is commenced. Debridement,
      drainage of any abscesses, spinal decompression and stabilization are options in
      surgical treatment. The successful use of metallic implants to achieve correction
      and stabilization is probably helped by good perfusion of the vertebral body and
      accompanying good soft tissue coverage. The eradication of infection is therefore
      still possible.

PMID- 10952850
TI  - Peculiarities of osteo-articular infections in children.
AB  - Paediatric osteomyelitis is uncommon in the developed world, haematogenous spread
      of infection being the most prevalent cause in children. The metaphyses of the
      long bones are the sites involved in most cases, but in neonates the infection
      may spread to the contiguous epiphysis and joint. Staphylococcus aureus is the
      main causal organism in all groups. Plain X-rays take at least 7 days to show the
      first signs of osteomyelitis. Bone scans show change earlier, with a high
      sensitivity but a lower specificity. Magnetic resonance imaging and computed
      tomography are useful, if expensive, imaging techniques but usually require
      sedation in children. The causal micro-organisms may be identified from blood
      cultures, fine-needle aspiration or surgical drainage. Antimicrobial therapy
      should be given for 3-4 weeks, initially via the intravenous route and later
      switching to oral medication. Surgery is indicated for the drainage of acute
      abscesses or when there has been no improvement with antibiotics; it is essential
      in the treatment of chronic osteomyelitis.

PMID- 10952851
TI  - Soft tissue and muscular infections (including group A streptococci).
AB  - Skin, soft tissue and muscular infections are very common and can progress to
      induce serious life-threatening local and systemic complications. They often
      occur in sites that have been compromised or injured by foreign bodies, trauma,
      ischaemia, malignancy or surgery. In addition to group A streptococci and
      Staphylococcus aureus, the indigenous local microflora is usually responsible for
      these infections. Anatomical sites that are subject to faecal or oral
      contamination are particularly at risk. The early recognition and proper medical
      and surgical management of these infections are of primary importance.

PMID- 10952852
TI  - Soft tissues and osteo-articular infections in HIV-infected patients and other
      immunodeficient states.
AB  - Soft tissue and osteo-articular infections are rarely seen in patients with HIV
      infection and other immunodeficiency states. When present in HIV-infected
      patients, they tend to occur in the presence of low CD4(+)cell counts,
      intravascular indwelling catheters, extra-articular infection and trauma, and in
      intravenous drug users and haemophiliacs. A wide spectrum of clinical
      manifestations is seen, ranging from cellulitis and soft tissue abscesses to
      septic arthritis and pyomyositis. In general, the clinical picture and response
      to therapy is similar to that of patients without HIV infection. Causal micro
      organisms are also similar to those in non-HIV populations, Staphylococcus aureus
      being the most common aetiological agent.

PMID- 10952853
TI  - Acute and chronic adult osteomyelitis and prosthesis-related infections.
AB  - Both acute and chronic osteomyelitis are causes of rising concern, mainly because
      of the increasing number of traumatic accidents, the appearance of new groups of
      patients at risk, the widespread use of prosthetic devices and the emergence of
      new patterns of antimicrobial resistance. Classification systems, clinical
      features and risk factors will be reviewed. Diagnosis is usually clinical and
      microbiological, but imaging techniques such as plain radiography, radionuclide
      imaging, computed tomography and magnetic resonance imaging are commonly used.
      Decisions regarding the best imaging modality can be challenging and should
      reflect the location of the suspected infection and any associated illnesses or
      bone disorders. Osteomyelitis is characteristically recurrent, needs multiple
      surgical interventions and is resistant to short courses of therapy. The
      application of more precise diagnostic techniques and the availability of non
      toxic, highly efficacious oral antimicrobial agents frequently permit a long-term
      ambulatory approach. The optimal length of therapy has not been established.

PMID- 10952854
TI  - Diagnosis and treatment of diabetic foot infections.
AB  - Prompt clinical diagnosis and timely treatment are the hallmarks of the proper
      care of diabetic patients with foot infections. The importance of careful
      clinical foot examination cannot be overemphasized. When infection is suspected,
      effort should be made to search for deeper infections, especially osteomyelitis.
      Numerous imaging techniques are available, but their cost-effectiveness has not
      been fully determined. Radiography of the foot is less sensitive but can provide
      useful information at a lower cost. Radio-isotope studies have not yielded
      consistent results, but the newer techniques deserve attention. Microbiological
      diagnosis should be attempted using only deep tissue culture, including bone
      biopsy. The primary aim of treatment of the infected foot is to restore
      ambulation. Timely surgical intervention and appropriate antimicrobial therapy
      can reduce the incidence of above-ankle amputation and reduce the length of
      hospital stay.

PMID- 10952855
TI  - Skeletal tuberculosis and other granulomatous infections.
AB  - After several decades of steadily decreasing incidence, tuberculosis has had a
      resurgence in the past 15 years, not only in the lungs, but also in
      extrapulmonary sites. This is primarily a result of the AIDS pandemic,
      considering that HIV specifically affects cellular immunity, which is the first
      line defence against tuberculosis. The generally non-specific clinical and
      radiological patterns of skeletal tuberculosis make it similar to other
      bacterial, fungal, inflammatory and neoplastic diseases of the bones and joints.
      Physicians must not omit tuberculosis in the differential diagnosis of any osteo
      articular inflammatory process so that specific treatment may be initiated as
      soon as possible. Anti-tuberculous therapy is beset by important factors that
      limit its efficacy, such as the emergence of drug toxicity and of resistant or
      multiresistant mycobacterial strains. Surgical treatment may be indicated in
      selected cases where medical therapy alone is not sufficient to eradicate the
      problem.

PMID- 10952856
TI  - Septic and aseptic arthritis: a continuum?
AB  - This chapter considers the likelihood that a wide spectrum of infection-provoked
      arthritis exists, ranging from overt sepsis to apparently aseptic chronic
      arthritis in which very small numbers of causal bacteria can be detected only by
      using highly sensitive techniques. It asks whether joints are, as conventionally
      held, normally devoid of micro-organisms and how to judge the significance of
      bacteria detected within apparently sterile joints. Through a consideration of
      known septic, probably infective and apparently aseptic forms of arthritis, a set
      of criteria for attributing causality to putative arthritogenic micro-organisms
      is proposed.

PMID- 10952857
TI  - Index

PMID- 10952858
TI  - Preface

PMID- 10952859
TI  - Editorial

PMID- 10952860
TI  - Frequency and impact of regional musculoskeletal disorders.
AB  - Regional musculoskeletal disorders are a major cause of morbidity both in the
      community and in the workplace. They comprise a heterogeneous group of conditions
      that are, for the most part, poorly characterized. Consequently, agreed
      diagnostic criteria have not existed for many of these disorders, and
      epidemiological investigations have used varied or ill-defined approaches to case
      definition. This chapter describes our current understanding of the epidemiology
      of regional pain disorders and details the strengths and weaknesses of the
      available data. Pain syndromes can be divided anatomically into those which cause
      generalized pain, such as fibromyalgia syndrome and myofascial pain syndromes,
      and those which are confined to one regional anatomical area. The latter group
      comprise those of the neck, shoulder, elbow, wrist/hand, hip, knee and
      ankle/foot. Current information is considered on the known risk factors for
      disorders at these sites, in addition to their impact upon both the individual
      and society.

PMID- 10952861
TI  - What are the mechanisms of regional musculoskeletal pain?
AB  - Pain is a subjective experience that is unique to the individual. Although pain
      is usually associated with tissue injury or inflammation, it is strongly
      influenced by changes within the nervous system as well as by psychological and
      social factors. This review focuses on those 'nociceptive' mechanisms which
      contribute to pain and demonstates how an appreciation of underlying molecular
      and cellular mechanisms can lead to improved diagnosis and treatment.

PMID- 10952862
TI  - Diagnosing regional pain: the view from primary care.
AB  - There is a general lack of new evidence on which to base practical and useful
      diagnostic classifications of regional musculoskeletal pain for primary care.
      However, the'red flag' system, developed and now disseminated successfully in the
      management of low back pain, seems to be applicable to the initial management of
      other regional pain. In this scheme, signs and symptoms of serious disease are
      sought, and their presence is the indication for the investigation or referral of
      individual patients. In their absence, the low predictive value of many signs,
      tests and even diagnostic labels argues against their routine use in primary
      care. Simple decisions based on separation into articular versus non-articular,
      and acute versus chronic, are favoured by the most recent expert consensus
      statements. In addition, the presence or absence of more widespread pain, and of
      other non-specific features of chronic pain, is likely to be helpful in managing
      regional syndromes. Prospective studies of the prognostic value of symptoms,
      signs and diagnostic labels remain a research priority in this field.

PMID- 10952863
TI  - Treatment options for regional musculoskeletal pain: what is the evidence?
AB  - Decisions about the best treatment options for patients with regional
      musculoskeletal pain must be made despite a lack of clear diagnostic criteria, an
      absence of robust outcome measures by which to assess response, and a paucity of
      evidence from high-quality randomized controlled trials. Although the randomized
      controlled trial is considered to be the 'gold standard' research design, it does
      not lend itself easily to the evaluation of all management strategies. This
      chapter explores these issues from a research perspective and reviews the various
      types of evidence available to help practitioners make informed decisions. The
      current evidence from systematic reviews in this area is summarized in the final
      part of the chapter.

PMID- 10952864
TI  - Regional musculoskeletal pain. The neck.
AB  - Tumours, infections, aneurysms and metabolic and inflammatory diseases are rare
      causes of neck pain. Most cases involve neck pain of unknown origin or a whiplash
      associated disorder. Neck pain is common in the general community and more common
      in certain occupations. The natural history is relatively benign, but some 10% of
      patients will suffer chronic, severe symptoms. Psychosocial factors have been
      refuted as risk factors; the cardinal risk factors relate to occupation. In
      whiplash, the severity of initial symptoms is the cardinal determinant of
      chronicity. History is the major factor when considering diagnosis, physical
      examination adding little to the diagnosis. Imaging is not indicated in the vast
      majority of cases. The available evidence does not support most of the physical,
      medical and surgical therapies currently practised. Confident reassurance is
      paramount and justified for acute cases. Proven options for chronic neck pain are
      few.

PMID- 10952865
TI  - Shoulder disorders: a state-of-the-art review.
AB  - This paper provides an up-to-date overview of the occurrence, diagnosis, risk
      factors, prognostic indicators and outcome of shoulder disorder (SD), and of the
      validity and reproducibility of diagnostic classifications and diagnostic imaging
      techniques for SD. Furthermore, the available evidence on the effectiveness of
      non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections and
      physiotherapy for SD is summarized on the basis of randomized controlled trials
      with an acceptable quality of their methods. The annual incidence of SD is
      estimated at about 7%, its 1-year period prevalence at about 51% and its lifetime
      prevalence at about 10%. While approximately 50% of all patients with SD seek
      medical care, about 95% are treated in primary health care. Of all new episodes
      of SD presenting to primary care, approximately 50% seem to resolve within 6
      months, while about 40% seem to persist for up to 12 months. Several prognostic
      indicators for a favourable or a poor outcome of SD have been identified, but a
      comprehensive prognostic model is not available. While evidence for the
      prognostic validity of popular diagnostic classifications of SD is lacking, their
      reproducibility has been shown to be poor. The accuracy and clinical usefulness
      of diagnostic imaging techniques appear to be sufficiently verified for SD in
      secondary care, while their clinical usefulness in primary care and prognostic
      validity are not. NSAIDs and steroid injections for SD have been shown to be
      effective within 6 weeks, but their effect on long-term outcome remains unclear.
      There is very limited evidence for the effectiveness in SD of physiotherapy,
      including exercise therapy, ultrasound, electrotherapy, laser, mobilization and
      manipulation.

PMID- 10952866
TI  - Regional musculoskeletal pain. The elbow, forearm, wrist and hand.
AB  - Two main groups of soft-tissue disorders are identified: specific soft tissue
      syndromes and a non-specific disorder as yet not fully characterized. Specific
      soft tissue syndromes occur in joint, muscle or nerve and are associated with
      characteristic symptoms and physical signs. These include epicondylitis at the
      elbow, tendon disorders at the wrist and nerve entrapments such as carpal tunnel
      syndrome. The non-specific soft tissue syndrome is primarily described by
      symptoms of pain but may include muscular symptoms (such as weakness and cramp)
      or nerve symptoms (such as numbness, pins and needles, and burning). Agreed,
      validated diagnostic criteria for use in surveillance are urgently required.
      Biological markers are still sought; both muscle and nerve seem promising for
      future studies. The multifactorial aetiology of these disorders will be
      discussed, and guidelines to management will embrace the principles of this
      model. Treatments aimed at the pain in isolation are most often studied.
      Psychosocial and environmental influences on the presentation and persistence of
      pain need further evaluation.

PMID- 10952867
TI  - Regional musculoskeletal pain. The knee.
AB  - Chronic knee pain is common at all ages, particularly in the elderly, among whom
      it has its greatest impact. Chronic knee pain is often ascribed to osteoarthritis
      in adults and to chondromalacia patellae in children and adolescents.
      Pathological findings in both these conditions correlate poorly, however, with
      the severity of knee pain and disability. Psychometric variables correlate better
      with the impact of knee osteoarthritis, suggesting that this disorder has
      characteristics of a regional pain syndrome. This perception may reflect our lack
      of understanding of the biological mechanisms in these disorders. This
      possibility has been highlighted by the advent of magnetic resonance imaging, and
      by recent studies of muscle function, reflex quadriceps inhibition and
      proprioception in people with knee osteoarthritis. Established risk factors for
      knee osteoarthritis include increased body weight, knee injury and aspects of
      occupational activity. Recent studies have also suggested a possible role for
      oestrogens and vitamins C and D in the secondary prevention of this disorder. The
      emergence of 'nutraceuticals' such as glucosamine as treatments for
      osteoarthritis has captured the public imagination and merits further study.

PMID- 10952868
TI  - Regional soft tissue pains: alias myofascial pain?
AB  - This chapter deals with four main questions: what is the evidence that
      'myofascial pain' syndromes exist?; what is the evidence that the myofascial pain
      concept is clinically useful?; what is the evidence that managing patients in
      terms of the myofascial pain diagnosis confers benefits?; and what is the
      evidence-based management of myofascial pain? The purpose of a diagnosis is to
      provide boundaries around subgroups of illness in a population since each
      subgroup presumably has a different mechanism, natural history, prognosis, course
      and response to treatment. The current literature is divided in its conceptual
      approach to the problem of regional musculoskeletal pain. Some authors regard
      myofascial pain as being distinct from regional musculoskeletal pain while others
      regard these as synonymous. A postulated theory of the pathophysiology of
      myofascial pain is discussed. This contrasts with a view that regional myofascial
      pain represents a non-specific localized pain arising from multiple regional,
      systemic and psychosocial factors. In order to consider myofascial pain as a
      distinct diagnosis, it would be necessary to resolve reliability issues in the
      identification of its critical diagnostic features. Beyond reliability issues,
      there are also problems of sensitivity and specificity--i.e. of the patient
      population that it identifies--which must be resolved if controlled trials are to
      be conducted. The clinical usefulness of the myofascial pain diagnosis is
      considered with regard to what is believed about the course of healing, the
      determinants of disability, the course of regional versus widespread
      musculoskeletal pain, the relationship of musculoskeletal injury to pain, and the
      evidence-based management of musculoskeletal pain. An epidemiological perspective
      is proposed with regard to regional musculoskeletal pain. This allows for the
      identification of operationally defined strata of regional musculoskeletal pain
      and permits studies in course, prognosis and treatment, even though some
      conceptual issues such as the 'myofascial pain diagnosis' remain to be clarified.

PMID- 10952870
TI  - Preface.

PMID- 10952872
TI  - Asynchronous muscle: a primer.
AB  - The asynchronous muscles of insects are characterized by asynchrony between
      muscle electrical and mechanical activity, a fibrillar organization with poorly
      developed sarcoplasmic reticulum, a slow time course of isometric contraction,
      low isometric force, high passive stiffness and delayed stretch activation and
      shortening deactivation. These properties are illustrated by comparing an
      asynchronous muscle, the basalar flight muscle of the beetle Cotinus mutabilis,
      with synchronous wing muscles from the locust, Schistocerca americana. Because of
      delayed stretch activation and shortening deactivation, a tetanically stimulated
      beetle muscle can do work when subjected to repetitive lengthening and
      shortening. The synchronous locust muscle, subjected to similar stimulation and
      length change, absorbs rather than produces work.

PMID- 10952871
TI  - A novel nemaline myopathy in the Amish caused by a mutation in troponin T1.
AB  - The nemaline myopathies are characterized by weakness and eosinophilic, rodlike
      (nemaline) inclusions in muscle fibers. Amish nemaline myopathy is a form of
      nemaline myopathy common among the Old Order Amish. In the first months of life,
      affected infants have tremors with hypotonia and mild contractures of the
      shoulders and hips. Progressive worsening of the proximal contractures, weakness,
      and a pectus carinatum deformity develop before the children die of respiratory
      insufficiency, usually in the second year. The disorder has an incidence of
      approximately 1 in 500 among the Amish, and it is inherited in an autosomal
      recessive pattern. Using a genealogy database, automated pedigree software, and
      linkage analysis of DNA samples from four sibships, we identified an
      approximately 2-cM interval on chromosome 19q13.4 that was homozygous in all
      affected individuals. The gene for the sarcomeric thin-filament protein, slow
      skeletal muscle troponin T (TNNT1), maps to this interval and was sequenced. We
      identified a stop codon in exon 11, predicted to truncate the protein at amino
      acid 179, which segregates with the disease. We conclude that Amish nemaline
      myopathy is a distinct, heritable, myopathic disorder caused by a mutation in
      TNNT1.

PMID- 10952873
TI  - Relationships between body mass, motor output and flight variables during free
      flight of juvenile and mature adult locusts, Schistocerca gregaria.
AB  - Little information is available about how the adult locust flight system manages
      to match the aerodynamic demands that result from an increase in body mass during
      postmoult maturation. In Schistocerca gregaria of both sexes, flight variables,
      including flight speed, ascent angle and body angle, were investigated under
      closed-loop conditions (i.e. during free flight) as a function of adult
      maturation. Motor patterns were examined by telemetric electromyography in
      juvenile and adult mature animals of both sexes. Functional relationships between
      particular flight variables were investigated by additional loading of the
      animals and by reductions in wing area. The results indicate that an increase in
      flight speed as the flight system matures enables it to match the aerodynamic
      demands resulting from increases in body mass. Furthermore, the data suggest that
      this postmoult increase in flight speed is not simply a consequence of the
      increase in wingbeat frequency observed during maturation. The instantaneous body
      angle during flight is controlled mainly by aerodynamic output from the wings. In
      addition, the mean body angle decreases during maturation in both sexes, and this
      may play an important part in the directional control of the resultant flight
      force vector.

PMID- 10952874
TI  - In vivo demonstration of load-induced fluid flow in the rat tibia and its
      potential implications for processes associated with functional adaptation.
AB  - Load-induced extravascular fluid flow has been postulated to play a role in
      mechanotransduction of physiological loads at the cellular level. Furthermore,
      the displaced fluid serves as a carrier for metabolites, nutrients, mineral
      precursors and osteotropic agents important for cellular activity. We hypothesise
      that load-induced fluid flow enhances the transport of these key substances, thus
      helping to regulate cellular activity associated with processes of functional
      adaptation and remodelling. To test this hypothesis, molecular tracer methods
      developed previously by our group were applied in vivo to observe and quantify
      the effects of load-induced fluid flow under four-point-bending loads.
      Preterminal tracer transport studies were carried out on 24 skeletally mature
      Sprague Dawley rats. Mechanical loading enhanced the transport of both small- and
      larger-molecular-mass tracers within the bony tissue of the tibial mid-diaphysis.
      Mechanical loading showed a highly significant effect on the number of
      periosteocytic spaces exhibiting tracer within the cross section of each bone.
      For all loading rates studied, the concentration of Procion Red tracer was
      consistently higher in the tibia subjected to pure bending loads than in the
      unloaded, contralateral tibia. Furthermore, the enhancement of transport was
      highly site-specific. In bones subjected to pure bending loads, a greater number
      of periosteocytic spaces exhibited the presence of tracer in the tension band of
      the cross section than in the compression band; this may reflect the higher
      strains induced in the tension band compared with the compression band within the
      mid-diaphysis of the rat tibia. Regardless of loading mode, the mean difference
      between the loaded side and the unloaded contralateral control side decreased
      with increasing loading frequency. Whether this reflects the length of exposure
      to the tracer or specific frequency effects cannot be determined by this set of
      experiments. These in vivo experimental results corroborate those of previous ex
      vivo and in vitro studies. Strain-related differences in tracer distribution
      provide support for the hypothesis that load-induced fluid flow plays a
      regulatory role in processes associated with functional adaptation.

PMID- 10952875
TI  - Temporal and spatial expression of the cell-cycle regulator cul-1 in Drosophila
      and its stimulation by radiation-induced apoptosis.
AB  - Cul-1 protein is part of the ubiquitin ligase complex that is conserved from
      yeast to humans. This complex specifically marks cell-cycle regulators for their
      subsequent destruction. Two null mutations of the cul-1 gene are known, in
      budding yeast and in nematodes. Although in both these organisms the cul-1 gene
      executes essentially the same function, the manifestation of its lack-of-function
      mutations differs considerably. In yeast the mutation causes arrest at the G(1)/S
      phase transition, whereas in nematodes excessive cell divisions occur because
      mutant cells are unable to exit the mitotic cycle. We isolated cul-1 orthologues
      from two model organisms, Drosophila melanogaster and mouse. We show that the
      Drosophila full-length cul-1 gene restores the yeast mutant's inability to pass
      through the G(1)/S-phase transition. We also characterize expression of this gene
      at the transcript and protein levels during Drosophila development and show that
      cul-1 gene is maternally supplied as a protein, but not as an RNA transcript.
      Zygotic transcription of the gene, however, resumes at early stages of
      embryogenesis. We also found an increase in cul-1 transcription in cultured cells
      treated with a lethal dose of gamma-irradiation.

PMID- 10952876
TI  - Ontogenetic scaling of burrowing forces in the earthworm Lumbricus terrestris.
AB  - In hydrostatic skeletons, it is the internal fluid under pressure surrounded by a
      body wall in tension (rather than a rigid lever) that enables the stiffening of
      the organism, the antagonism of muscles and the transmission of force from the
      muscles to the environment. This study examined the ontogenetic effects of body
      size on force production by an organism supported with a hydrostatic skeleton.
      The earthworm Lumbricus terrestris burrows by forcefully enlarging crevices in
      the soil. I built a force-measuring apparatus that measured the radial forces as
      earthworms of different sizes crawled through and enlarged pre-formed soil
      burrows. I also built an apparatus that measured the radial and axial forces as
      earthworms of different sizes attempted to elongate a dead-end burrow. Earthworms
      ranging in body mass m(b) from hatchlings (0.012 g) to adults (8.9 g) exerted
      maximum forces (F, in N) during active radial expansion of their burrows (F=0.32
      m(b)(0.43)) and comparable forces during axial elongation of the burrow (F=0.26
      m(b)(0.47)). Both these forces were almost an order of magnitude greater than the
      radial anchoring forces during normal peristalsis within burrows (F=0.04
      m(b)(0.45)). All radial and axial forces scaled as body mass raised to the 2/5
      power rather than to the 2/3 power expected by geometric similarity, indicating
      that large worms exert greater forces than small worms on an absolute scale, but
      the difference was less than predicted by scaling considerations. When forces
      were normalized by body weight, hatchlings could push 500 times their own body
      weight, while large adults could push only 10 times their own body weight.

PMID- 10952877
TI  - Temperature-dependence of L-type Ca(2+) channel current in atrial myocytes from
      rainbow trout.
AB  - Rainbow trout, Oncorhynchus mykiss, inhabit eurythermal environments and must
      therefore be able to cope with changes in environmental temperature. As
      ectotherms, their heart is required to maintain cardiac function over a range of
      ambient water temperatures. This raises important questions concerning the
      temperature-dependence of cardiac ion channel function in fish hearts, in
      particular, the channels involved in Ca(2+) transport. Thus, we studied the
      effects of acute, physiologically relevant temperature changes on the density and
      kinetics of the L-type Ca(2+) channel current (I(Ca)) in rainbow trout atrial
      myocytes using the whole-cell patch-clamp technique. Myocytes from fish
      acclimated to 14 degrees C were first tested at 14 degrees C, then at 21 degrees
      C and finally at 7 degrees C. Using a square-pulse voltage-clamp in the first
      series of experiments, the peak density of I(Ca) increased (Q(10)=1.9) as
      temperature was increased from 14 to 21 degrees C and decreased (Q(10)=2.1) as
      temperature was decreased from 14 to 7 degrees C. In contrast to current density,
      the charge carried by I(Ca) was inversely related to temperature as a result of
      changes in the kinetic properties of the channel; both the fast (tau(f)) and slow
      (tau(s)) components of inactivation were slower at 7 degrees C than at 14 and 21
      degrees C. Action potentials were recorded at the three test temperatures and
      then used as voltage-clamp stimulus waveforms to reassess I(Ca) in a second
      series of experiments. While the temperature-dependency of I(Ca) was similar to
      that found with the square-pulse voltage-clamp, the charge carried by I(Ca) was
      temperature-independent. These results show that the temperature-dependency of
      I(Ca) in rainbow trout is in the lower range of that reported in mammals and,
      although this could have profound effects on Ca(2+) delivery to the myofilaments,
      the temperature-induced modifications in the action potential may help to
      maintain a fairly constant Ca(2+) delivery during an acute temperature change in
      rainbow trout.

PMID- 10952878
TI  - Durophagy in sharks: feeding mechanics of the hammerhead Sphyrna tiburo.
AB  - This study investigates the motor pattern and head movements during feeding of a
      durophagus shark, the bonnethead Sphyrna tiburo, using electromyography and
      simultaneous high-speed video. Sphyrna tiburo feeds almost exclusively on hard
      shelled crabs, with shrimp and fish taken occasionally. It captures crabs by ram
      feeding, then processes or reduces the prey by crushing it between molariform
      teeth, finally transporting the prey by suction for swallowing. The prey-crushing
      mechanism is distinct from that of ram or bite capture and suction transport.
      This crushing mechanism is accomplished by altering the duration of jaw adductor
      muscle activity and modifying jaw kinematics by the addition of a second jaw
      closing phase. In crushing events, motor activity of the jaw adductor muscles
      continues (biting of the prey occurs as the jaws close and continues after the
      jaws have closed) throughout a second jaw-closing phase, unlike capture and
      transport events during which motor activity (biting) ceases at jaw closure.
      Sphyrna tiburo is able to take advantage of a resource (hard prey) that is not
      readily available to most sharks by utilizing a suite of durophagous
      characteristics: molariform teeth, a modified jaw protrusor muscle, altered jaw
      adductor activity and modified jaw kinematics. Sphyrna tiburo is a specialist
      feeder on crab prey as demonstrated by the lack of differences in kinematic or
      motor patterns when offered prey of differing hardness and its apparent lack of
      ability to modulate its behavior when feeding on other prey. Functional patterns
      are altered and coupled with modifications in dental and jaw morphology to
      produce diverse crushing behaviors in elasmobranchs.

PMID- 10952879
TI  - Blocking and the detection of odor components in blends.
AB  - Recent studies of olfactory blocking have revealed that binary odorant mixtures
      are not always processed as though they give rise to mixture-unique configural
      properties. When animals are conditioned to one odorant (A) and then conditioned
      to a mixture of that odorant with a second (X), the ability to learn or express
      the association of X with reinforcement appears to be reduced relative to animals
      that were not preconditioned to A. A recent model of odor-based response patterns
      in the insect antennal lobe predicts that the strength of the blocking effect
      will be related to the perceptual similarity between the two odorants, i.e.
      greater similarity should increase the blocking effect. Here, we test that model
      in the honeybee Apis mellifera by first establishing a generalization matrix for
      three odorants and then testing for blocking between all possible combinations of
      them. We confirm earlier findings demonstrating the occurrence of the blocking
      effect in olfactory learning of compound stimuli. We show that the occurrence and
      the strength of the blocking effect depend on the odorants used in the
      experiment. In addition, we find very good agreement between our results and the
      model, and less agreement between our results and an alternative model recently
      proposed to explain the effect.

PMID- 10952880
TI  - Two orcokinins and the novel octapeptide orcomyotropin in the hindgut of the
      crayfish Orconectes limosus: identified myostimulatory neuropeptides originating
      together in neurones of the terminal abdominal ganglion.
AB  - The tridecapeptides Asn(13)-orcokinin and Val(13)-orcokinin, two known members of
      the orcokinin neuropeptide family native to crustaceans, and a novel octapeptide,
      orcomyotropin, FDAFTTGFamide, have been identified from extracts of hindguts of
      the crayfish Orconectes limosus using an isolated hindgut contractility bioassay,
      high-performance liquid chromatography, microsequencing and mass spectrometry.
      All three peptides display strong inotropic actions on crayfish hindguts.
      Orcomyotropin showed higher potency than the two orcokinins. Threshold
      concentration was approximately 5 x 10(-12)mol l(-1)versus 10(-10)mol l(-1) for
      the two orcokinins. An approximately fivefold increase in contraction amplitude
      was observed with 10(-9)mol l(-1) orcomyotropin and 10(-7)mol l(-1) of the
      orcokinins. Asn(13)- and Val(13)-orcokinin did not differ significantly with
      regard to their biological effects. Semi-isolated crayfish hearts and locust
      oviducts did not respond to the three peptides. Immunocytochemistry using
      antisera against Asn(13)-orcokinin and orcomyotropin showed that these
      neuropeptides are co-localized in approximately 80-90 neurones of the terminal
      abdominal ganglion that have been shown to innervate the entire hindgut
      muscularis via the intestinal nerve. The neurones form elaborate terminal
      branches preferentially on longitudinal hindgut muscles. Orcomyotropin is a novel
      crustacean member of the GF-amide family of myotropic and/or allatotropic
      neuropeptides from annelids, molluscs and insects.

PMID- 10952881
TI  - Estimation of the rate of oxygen consumption of the common eider duck (Somateria
      mollissima), with some measurements of heart rate during voluntary dives.
AB  - The relationship between heart rate (f(H)) and rate of oxygen consumption (V(O2))
      was established for a marine diving bird, the common eider duck (Somateria
      mollissima), during steady-state swimming and running exercise. Both variables
      increased exponentially with speed during swimming and in a linear fashion during
      running. Eleven linear regressions of V(O2) (ml kg(-1 )min(-1)) on f(H) (beats
      min(-1)) were obtained: five by swimming and six by running the birds. The common
      regression was described by V(O2)=10.1 + 0.15f(H) (r(2)=0.46, N=272, P<0.0001).
      The accuracy of this relationship for predicting mean V(O2) was determined for a
      group of six birds by recording f(H) continuously over a 2-day period and
      comparing estimated V(O2) obtained using the common regression with (i) V(O2)
      estimated using the doubly labelled water technique (DLW) and (ii) V(O2) measured
      using respirometry. A two-pool model produced the most accurate estimated V(O2)
      using DLW. Because of individual variability within mean values of V(O2)
      estimated using both techniques, there was no significant difference between mean
      V(O2) estimated using f(H) or DLW and measured V(O2) values (P>0.2), although
      individual errors were substantially less when f(H) was used rather than DLW to
      estimate V(O2). Both techniques are, however, only suitable for estimating mean
      V(O2) for a group of animals, not for individuals. Heart rate and behaviour were
      monitored during a bout of 63 voluntary dives by one female bird in an indoor
      tank 1.7 m deep. Tachycardia occurred both in anticipation of and following each
      dive. Heart rate decreased before submersion but was above resting values for the
      whole of the dive cycle. Mean f(H) at mean dive duration was significantly
      greater than f(H) while swimming at maximum sustainable surface speeds. Heart
      rate was used to estimate mean V(O2) during the dive cycle and to predict aerobic
      dive limit (ADL) for shallow dives.

PMID- 10952882
TI  - Comparative study of tongue protrusion in three iguanian lizards, Sceloporus
      undulatus, Pseudotrapelus sinaitus and Chamaeleo jacksonii.
AB  - The goal of this study was to investigate the function of the hyolingual muscles
      used during tongue protraction in iguanian lizards. High-speed videography and
      nerve-transection techniques were used to study prey capture in the iguanid
      Sceloporus undulatus, the agamid Pseudoptrapelus sinaitus and the chameleonid
      Chamaeleo jacksonii. Denervation of the mandibulohyoideus muscle slips had an
      effect only on P. sinaitus and C. jacksonii, in which tongue protrusion or
      projection distance was reduced. In C. jacksonii, denervation of the M.
      mandibulohyoideus completely prevented little hyoid protraction. Denervation of
      the M. verticalis had no effect on S. undulatus, but reduced tongue protrusion
      distance in P. sinaitus. Denervation of the accelerator muscle in C. jacksonii
      inhibited tongue projection completely. The function of the M. mandibulohyoideus
      and M. verticalis has become increasingly specialized in P. sinaitus and
      especially in C. jacksonii to allow greater tongue protrusion. The combined
      results of these treatments suggest that these three groups represent
      transitional forms, both morphologically and functionally, in the development of
      a projectile tongue.

PMID- 10952883
TI  - The mechanics of locomotion in the squid Loligo pealei: locomotory function and
      unsteady hydrodynamics of the jet and intramantle pressure.
AB  - High-speed, high-resolution digital video recordings of swimming squid (Loligo
      pealei) were acquired. These recordings were used to determine very accurate
      swimming kinematics, body deformations and mantle cavity volume. The time-varying
      squid profile was digitized automatically from the acquired swimming sequences.
      Mantle cavity volume flow rates were determined under the assumption of
      axisymmetry and the condition of incompressibility. The data were then used to
      calculate jet velocity, jet thrust and intramantle pressure, including unsteady
      effects. Because of the accurate measurements of volume flow rate, the standard
      use of estimated discharge coefficients was avoided. Equations for jet and whole
      cycle propulsive efficiency were developed, including a general equation
      incorporating unsteady effects. Squid were observed to eject up to 94 % of their
      intramantle working fluid at relatively high swimming speeds. As a result, the
      standard use of the so-called large-reservoir approximation in the determination
      of intramantle pressure by the Bernoulli equation leads to significant errors in
      calculating intramantle pressure from jet velocity and vice versa. The failure of
      this approximation in squid locomotion also implies that pressure variation
      throughout the mantle cannot be ignored. In addition, the unsteady terms of the
      Bernoulli equation and the momentum equation proved to be significant to the
      determination of intramantle pressure and jet thrust. Equations of propulsive
      efficiency derived for squid did not resemble Froude efficiency. Instead, they
      resembled the equation of rocket motor propulsive efficiency. The Froude equation
      was found to underestimate the propulsive efficiency of the jet period of the
      squid locomotory cycle and to overestimate whole-cycle propulsive efficiency when
      compared with efficiencies calculated from equations derived with the squid
      locomotory apparatus in mind. The equations for squid propulsive efficiency
      reveal that the refill period of squid plays a greater role, and the jet period a
      lesser role, in the low whole-cycle efficiencies predicted in squid and similar
      jet-propelled organisms. These findings offer new perspectives on locomotory
      hydrodynamics, intramantle pressure measurements and functional morphology with
      regard to squid and other jet-propelled organisms.

PMID- 10952884
TI  - Inspiratory aerodynamic valving in the avian lung: functional morphology of the
      extrapulmonary primary bronchus.
AB  - The form, geometry and epithelial morphology of the extrapulmonary primary
      bronchi (EPPB) of the domestic fowl (Gallus gallus var. domesticus) and the rock
      dove (Columba livia) were studied microscopically and by three-dimensional
      computer reconstruction to determine the structural features that may be involved
      in the rectification of the inspired air past the openings of the medioventral
      secondary bronchi (MVSB), i.e. the inspiratory aerodynamic valving (IAV). In both
      species, the EPPB were intercalated between the clavicular and the cranial
      thoracic air-sacs. A notable difference between the morphology of the EPPB in G.
      g. domesticus and C. livia was that, in the former, the EPPB were constricted at
      the origin of the MVSB, while a dilatation occurred at the same site in the
      latter. In both species, a highly vascularized, dorsally located hemispherical
      epithelial swelling was observed cranial to the origin of the MVSB. The MVSB were
      narrow at their origin and variably angled relative to the longitudinal axis of
      the EPPB. Conspicuous epithelial tracts and folds were observed on the luminal
      aspect of the EPPB in both C. livia and G. g. domesticus. From their marked
      development and their orientation relative to the angled MVSB, these properties
      may influence the flow of the air in the EPPB. It was concluded that features
      such as syringeal constriction, an intimate topographic relationship between the
      EPPB and the cranial air-sacs, prominent epithelial tracts and folds, an
      epithelial swelling ahead of the origin of the first MVSB (corresponding to the
      'segmentun accelerans'), and narrowing and angulation of the MVSB at their
      origin, may together contribute to IAV to a variable extent. In as much as the
      mechanism of pulmonary ventilation and mode of airflow in the parabronchial lung
      are basically similar in all birds, the morphological differences observed
      between G. g. domesticus and C. livia suggest that either the mechanism of
      production of IAV or its functional efficiency may be different, at least in
      these two species of birds.

PMID- 10952885
TI  - Integumentary L-histidine transport in a euryhaline polychaete worm: regulatory
      roles of calcium and cadmium in the transport event.
AB  - Integumentary uptake of L-[(3)H]histidine by polychaete worms (Nereis succinea)
      from estuarine waters of Oahu, Hawaii was measured in the presence and absence of
      calcium and cadmium using a physiological saline that approximated the ion
      composition of 60 % sea water. In this medium 1 micromol L(-1) cadmium
      significantly increased (P<0.01) the uptake of 10 micromol L(-1)L
      [(3)H]histidine, while 1 micromol L(-1) cadmium plus 25 micromol L(-1)L-leucine
      significantly decreased (P<0.01) amino acid uptake. L-[(3)H]histidine influx was
      a sigmoidal function (n=2. 21+/-0.16, mean +/- s.e.m.) of [L-histidine] (1?50
      micromol L(-1)) in the absence of cadmium, but became a hyperbolic function with
      the addition of 1 micromol L(-1) cadmium. A decrease of calcium concentration
      from 6 to 0 mmol L(-1) (lithium substitution) significantly increased (P<0.01)
      amino acid influx in the presence and absence of cadmium. Calcium significantly
      reduced (P<0.01), and cadmium significantly increased (P<0.01), L-[(3)H]histidine
      influx J(max), without either divalent cation affecting amino acid influx K(t).
      Variation in external sodium concentration (0?250 mmol L(-1)) had no effect on 10
      micromol L(-1)L-[(3)H]histidine influx, but amino acid entry was a sigmoidal
      function of both [cadmium] (n=2.34+/-0.44) and [lithium] (n=1.91+/-0.39) in the
      absence of calcium. A model is proposed for transapical L-[(3)H]histidine influx
      by a transporter that resembles the classical sodium-independent L-system carrier
      protein that is regulated by the external divalent cations calcium and cadmium.

PMID- 10952886
TI  - Auxin and ETTIN in Arabidopsis gynoecium morphogenesis.
AB  - The phytohormone auxin has wide-ranging effects on growth and development.
      Genetic and physiological approaches implicate auxin flux in determination of
      floral organ number and patterning. This study uses a novel technique of
      transiently applying a polar auxin transport inhibitor, N-1-naphthylphthalamic
      acid (NPA), to developing Arabidopsis flowers to further characterize the role of
      auxin in organogenesis. NPA has marked effects on floral organ number as well as
      on regional specification in wild-type gynoecia, as defined by morphological and
      histological landmarks for regional boundaries, as well as tissue-specific
      reporter lines. NPA's effects on gynoecium patterning mimic the phenotype of
      mutations in ETTIN, a member of the auxin response factor family of transcription
      factors. In addition, application of different concentrations of NPA reveal an
      increased sensitivity of weak ettin alleles to disruptions in polar auxin
      transport. In contrast, the defects found in spatula gynoecia are partially
      rescued by treatment with NPA. A model is proposed suggesting an apical-basal
      gradient of auxin during gynoecium development. This model provides a mechanism
      linking ETTIN's putative transcriptional regulation of auxin-responsive genes to
      the establishment or elaboration of tissue patterning during gynoecial
      development.

PMID- 10952887
TI  - Direct action of the nodal-related signal cyclops in induction of sonic hedgehog
      in the ventral midline of the CNS.
AB  - The secreted molecule Sonic hedgehog (Shh) is crucial for floor plate and ventral
      brain development in amniote embryos. In zebrafish, mutations in cyclops (cyc), a
      gene that encodes a distinct signal related to the TGF(beta) family member Nodal,
      result in neural tube defects similar to those of shh null mice. cyc mutant
      embryos display cyclopia and lack floor plate and ventral brain regions,
      suggesting a role for Cyc in specification of these structures. cyc mutants
      express shh in the notochord but lack expression of shh in the ventral brain.
      Here we show that Cyc signalling can act directly on shh expression in neural
      tissue. Modulation of the Cyc signalling pathway by constitutive activation or
      inhibition of Smad2 leads to altered shh expression in zebrafish embryos. Ectopic
      activation of the shh promoter occurs in response to expression of Cyc signal
      transducers in the chick neural tube. Furthermore an enhancer of the shh gene,
      which controls ventral neural tube expression, is responsive to Cyc signal
      transducers. Our data imply that the Nodal related signal Cyc induces shh
      expression in the ventral neural tube. Based on the differential responsiveness
      of shh and other neural tube specific genes to Hedgehog and Cyc signalling, a two
      step model for the establishment of the ventral midline of the CNS is proposed.

PMID- 10952888
TI  - Maternally controlled (beta)-catenin-mediated signaling is required for organizer
      formation in the zebrafish.
AB  - We have identified and characterized a zebrafish recessive maternal effect
      mutant, ichabod, that results in severe anterior and dorsal defects during early
      development. The ichabod mutation is almost completely penetrant, but exhibits
      variable expressivity. All mutant embryos fail to form a normal embryonic shield;
      most fail to form a head and notochord and have excessive development of ventral
      tail fin tissue and blood. Abnormal dorsal patterning can first be observed at
      3.5 hpf by the lack of nuclear accumulation of (beta)-catenin in the dorsal yolk
      syncytial layer, which also fails to express bozozok/dharma/nieuwkoid and
      znr2/ndr1/squint. At the onset of gastrulation, deficiencies in expression of
      dorsal markers and expansion of expression of markers of ventral tissues indicate
      a dramatic alteration of dorsoventral identity. Injection of (beta)-catenin RNA
      markedly dorsalized ichabod embryos and often completely rescued the phenotype,
      but no measurable dorsalization was obtained with RNAs encoding upstream Wnt
      pathway components. In contrast, dorsalization was obtained when RNAs encoding
      either Bozozok/Dharma/Nieuwkoid or Znr2/Ndr1/Squint were injected. Moreover,
      injection of (beta)-catenin RNA into ichabod embryos resulted in activation of
      expression of these two genes, which could also activate each other. RNA
      injection experiments strongly suggest that the component affected by the ichabod
      mutation acts on a step affecting (beta)-catenin nuclear localization that is
      independent of regulation of (beta)-catenin stability. This work demonstrates
      that a maternal gene controlling localization of (beta)-catenin in dorsal nuclei
      is necessary for dorsal yolk syncytial layer gene activity and formation of the
      organizer in the zebrafish.

PMID- 10952889
TI  - Basic helix-loop-helix transcription factors regulate the neuroendocrine
      differentiation of fetal mouse pulmonary epithelium.
AB  - To clarify the mechanisms that regulate neuroendocrine differentiation of fetal
      lung epithelia, we have studied the expression of the mammalian homologs of
      achaete-scute complex (Mash1) (Ascl1 - Mouse Genome Informatics); hairy and
      enhancer of split1 (Hes1); and the expression of Notch/Notch-ligand system in the
      fetal and adult mouse lungs, and in the lungs of Mash1- or Hes1-deficient mice.
      Immunohistochemical studies revealed that Mash1-positive cells seemed to belong
      to pulmonary neuroendocrine cells (PNEC) and their precursors. In mice deficient
      for Mash1, no PNEC were detected. Hes1-positive cells belong to non
      neuroendocrine cells. In the mice deficient in Hes1, in which Mash1 mRNA was
      upregulated, PNEC appeared precociously, and the number of PNEC was markedly
      increased. NeuroD (Neurod1 - Mouse Genome Informatics) expression in the lung was
      detected in the adult, and was enhanced in the fetal lungs of Hes1-null mice.
      Expression of Notch1, Notch2, Notch3 and Notch4 mRNAs in the mouse lung increased
      with age, and Notch1 mRNA was expressed in a Hes1-dependent manner. Notch1,
      Notch2 and Notch3 were immunohistochemically detected in non-neuroendocrine
      cells. Moreover, analyses of the lungs from the gene-targeted mice suggested that
      expression of Delta-like 1 (Dll1 - Mouse Genome Informatics) mRNA depends on
      Mash1. Thus, the neuroendocrine differentiation depends on basic helix-loop-helix
      factors, and Notch/Notch-ligand pathways may be involved in determining the cell
      differentiation fate in fetal airway epithelium.

PMID- 10952890
TI  - A skeletal muscle-specific mouse Igf2 repressor lies 40 kb downstream of the
      gene.
AB  - Igf2 and H19 are closely linked and reciprocally expressed genes on distal
      chromosome 7 in the mouse. We have previously shown that a 130 kb YAC transgene
      contains multiple tissue-specific enhancers for expression of both genes during
      embryogenesis. The YAC also contains all the crucial elements responsible for
      initiating and maintaining appropriate parent-of-origin-specific expression of
      these genes at ectopic sites, with expression of Igf2 after paternal inheritance
      and of H19 after maternal inheritance. Located centrally between Igf2 and H19 are
      two prominent DNaseI hypersensitive sites, and two stretches of sequence that are
      conserved between mouse and human. In this study, we have deleted, from the
      transgene, a one kb part of the intergenic region that contains the
      hypersensitive sites and one of the homologous stretches. We demonstrate that
      this deletion results in loss of maternal Igf2 repression in skeletal muscle
      cells, most strikingly in the tongue, late in embryogenesis. We propose that the
      intergenic region functions as a tissue-specific repressor element, forming an
      integral part of the complex regulatory mechanism that controls monoallelic gene
      expression in this domain.

PMID- 10952891
TI  - SIAMESE, a gene controlling the endoreduplication cell cycle in Arabidopsis
      thaliana trichomes.
AB  - Cell differentiation is generally tightly coordinated with the cell cycle,
      typically resulting in a nondividing cell with a unique differentiated
      morphology. The unicellular trichomes of Arabidopsis are a well-established model
      for the study of plant cell differentiation. Here, we describe a new genetic
      locus, SIAMESE (SIM), required for coordinating cell division and cell
      differentiation during the development of Arabidopsis trichomes (epidermal
      hairs). A recessive mutation in the sim locus on chromosome 5 results in clusters
      of adjacent trichomes that appeared to be morphologically identical 'twins'. Upon
      closer inspection, the sim mutant was found to produce multicellular trichomes in
      contrast to the unicellular trichomes produced by wild-type (WT) plants. Mutant
      trichomes consisting of up to 15 cells have been observed. Scanning electron
      microscopy of developing sim trichomes suggests that the cell divisions occur
      very early in the development of mutant trichomes. WT trichome nuclei continue to
      replicate their DNA after mitosis and cytokinesis have ceased, and as a
      consequence have a DNA content much greater than 2C. This phenomenon is known as
      endoreduplication. Individual nuclei of sim trichomes have a reduced level of
      endoreduplication relative to WT trichome nuclei. Endoreduplication is also
      reduced in dark-grown sim hypocotyls relative to WT, but not in light-grown
      hypocotyls. Double mutants of sim with either of two other mutants affecting
      endoreduplication, triptychon (try) and glabra3 (gl3) are consistent with a
      function for SIM in endoreduplication. SIM may function as a repressor of mitosis
      in the endoreduplication cell cycle. Additionally, the relatively normal
      morphology of multicellular sim trichomes indicates that trichome morphogenesis
      can occur relatively normally even when the trichome precursor cell continues to
      divide. The sim mutant phenotype also has implications for the evolution of
      multicellular trichomes.

PMID- 10952892
TI  - Embryonic development is disrupted by modest increases in vascular endothelial
      growth factor gene expression.
AB  - Previous work has shown that heterozygocity for a null mutation of the VEGF-A
      gene, resulting in a 50% reduction in VEGF-A expression, is embryonic lethal at
      embroyonic day (E) 9.5 in mice. We now show that two- to threefold overexpression
      of VEGF-A from its endogenous locus results in severe abnormalities in heart
      development and embryonic lethality at E12.5-E14. The mutant embryos displayed an
      attenuated compact layer of myocardium, overproduction of trabeculae, defective
      ventricular septation and abnormalities in remodeling of the outflow track of the
      heart. In addition, aberrant coronary development was characterized by formation
      of oversized epicardial vessels, apparently through vasculogenesis. We infer that
      embryonic survival requires a narrow window of VEGF-A expression.

PMID- 10952893
TI  - Crossveinless 2 contains cysteine-rich domains and is required for high levels of
      BMP-like activity during the formation of the cross veins in Drosophila.
AB  - The BMP-like signaling mediated by the ligands Dpp and Gbb is required to
      reinforce the development of most veins in the Drosophila wing. However, the
      formation of the cross veins is especially sensitive to reductions in BMP-like
      signaling. We show here that the formation of the definitive cross veins occurs
      after the initial specification of the longitudinal veins in a process that
      requires localized BMP-like activity. Since Dpp and Gbb levels are not detectably
      higher in the early phases of cross vein development, other factors apparently
      account for this localized activity. Our evidence suggests that the product of
      the crossveinless 2 gene is a novel member of the BMP-like signaling pathway
      required to potentiate Gbb of Dpp signaling in the cross veins. crossveinless 2
      is expressed at higher levels in the developing cross veins and is necessary for
      local BMP-like activity. The Crossveinless 2 protein contains a putative signal
      or transmembrane sequence, and a partial Von Willebrand Factor D domain similar
      to those known to regulate the formation of intramolecular and intermolecular
      bonds. It also contains five cysteine-rich domains, similar to the cysteine-rich
      domains found in Chordin, Short Gastrulation and Procollagen that are known to
      bind BMP-like ligands. These features strongly suggest that Crossveinless 2 acts
      extracelluarly or in the secretory pathway to directly potentiate Dpp or Gbb
      signaling.

PMID- 10952894
TI  - Opposing RA and FGF signals control proximodistal vertebrate limb development
      through regulation of Meis genes.
AB  - Vertebrate limbs develop in a temporal proximodistal sequence, with proximal
      regions specified and generated earlier than distal ones. Whereas considerable
      information is available on the mechanisms promoting limb growth, those involved
      in determining the proximodistal identity of limb parts remain largely unknown.
      We show here that retinoic acid (RA) is an upstream activator of the proximal
      determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and
      endogenous RA signaling is required to maintain the proximal Meis domain in the
      limb. RA synthesis and signaling range, which initially span the entire lateral
      plate mesoderm, become restricted to proximal limb domains by the apical
      ectodermal ridge (AER) activity following limb initiation. We identify fibroblast
      growth factor (FGF) as the main molecule responsible for this AER activity and
      propose a model integrating the role of FGF in limb cell proliferation, with a
      specific function in promoting distalization through inhibition of RA production
      and signaling.

PMID- 10952895
TI  - Generation of medial and lateral dorsal body domains by the pannier gene of
      Drosophila.
AB  - The pannier (pnr) gene encodes a GATA transcription factor and acts in several
      developmental processes in Drosophila, including embryonic dorsal closure,
      specification of cardiac cells and bristle determination. We show that pnr is
      expressed in the mediodorsal parts of thoracic and abdominal segments of embryos,
      larvae and adult flies. Its activity confers cells with specific adhesion
      properties that make them immiscible with non-expressing cells. Thus there are
      two genetic domains in the dorsal region of each segment: a medial (MED) region
      where pnr is expressed and a lateral (LAT) region where it is not. The homeobox
      gene iroquois (iro) is expressed in the LAT region. These regions are not formed
      by separate polyclones of cells, but are defined topographically. We show that
      ectopic pnr in the wing induces MED thoracic development, indicating that pnr
      specifies the identity of the MED regions. Correspondingly, when pnr is removed
      from clones of cells in the MED domain, they sort out and apparently adopt the
      LAT fate. We propose that (1) the subdivision into MED and LAT regions is a
      general feature of the Drosophila body plan and (2) pnr is the principal gene
      responsible for this subdivision. We argue that pnr acts like a classical
      selector gene but differs in that its expression is not propagated through cell
      divisions.

PMID- 10952896
TI  - P element homing to the Drosophila bithorax complex.
AB  - P elements containing a 7 kb DNA fragment from the middle of the Drosophila
      bithorax complex insert preferentially into the bithorax complex or into the
      adjacent chromosome regions. This 'homing' property is similar to that reported
      for the engrailed promoter (Hama, C., Ali, Z. and Kornberg, T. B. (1990) Genes
      Dev. 4, 1079-1093). The 7 kb fragment does not contain any known promoter, but it
      acts as a boundary element separating adjacent segmental domains. An enhancer
      trap P element was constructed with the homing fragment and the selectable marker
      flanked by FRT sites. P insertions can be trimmed down by Flp-mediated
      recombination to just the lacZ reporter, so that the (beta)-galactosidase pattern
      is not influenced by sequences inside the P element. Twenty insertions into the
      bithorax complex express (beta)-galactosidase in segmentally limited patterns,
      reflecting the segmental domains of the bithorax complex where the elements
      reside. The mapping of segmental domains has now been revised, with enlargement
      of the abx/bx, bxd/pbx, and the iab-3 domains. The FRT sites in the P elements
      permit recombination between pairs of elements on opposite chromosomes, to
      generate duplications or deletions of the DNA between the two insertion sites.
      Using this technique, the length of the Ultrabithorax transcription unit was
      varied from 37 to 138 kb, but there was surprisingly little effect on
      Ultrabithorax function.

PMID- 10952897
TI  - High bicoid levels render the terminal system dispensable for Drosophila head
      development.
AB  - In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the
      anteroposterior axis while the ends of the embryo are patterned by the maternal
      terminal system. At the posterior pole, expression of terminal gap genes is
      mediated by the local activation of the Torso receptor tyrosine kinase (Tor). At
      the anterior, terminal gap genes are also activated by the Tor pathway but Bcd
      contributes to their activation. Here we present evidence that Tor and Bcd act
      independently on common target genes in an additive manner. Furthermore, we show
      that the terminal maternal system is not required for proper head development,
      since high levels of Bcd activity can functionally rescue the lack of terminal
      system activity at the anterior pole. This observation is consistent with a
      recent evolution of an anterior morphogenetic center consisting of Bcd and
      anterior Tor function.

PMID- 10952898
TI  - Suppressor of fused opposes hedgehog signal transduction by impeding nuclear
      accumulation of the activator form of Cubitus interruptus.
AB  - Hedgehog controls the expression of key developmental genes through the
      conversion of the transcription factor Cubitus interruptus (Ci) into either an
      activator (Ci[act]) or a repressor (Ci[rep]) form. Proteolytic cleavage of full
      length Ci is important for the generation of Ci[rep], but little is known about
      how Ci[act] arises in response to Hh. Here we examine Hh signal transduction
      components for their role in the conversion of full-length Ci into either Ci[act]
      or Ci[rep]. We report that Cos2, PKA and Fused are necessary for the generation
      of Ci[rep], whereas the inhibition of either Cos2 or PKA activity is a
      prerequisite for Ci[act] formation. Fused (Fu) kinase stimulates a constitutively
      active form of Ci in a Hh-dependent manner, suggesting that Fu enhances the
      activity rather than the formation of Ci[act]. Su(fu) reduces the nuclear
      accumulation of the constitutively active form of Ci, arguing that Su(fu) can
      function subsequent to Ci[act] formation. We propose that Hh induces target gene
      expression by a two-step mechanism in which Ci[act] is first formed and then
      accumulates in the nucleus via Fu-induced neutralization of Su(fu) activity.

PMID- 10952899
TI  - Distribution of polarizing activity and potential for limb formation in mouse and
      chick embryos and possible relationships to polydactyly.
AB  - A central feature of the tetrapod body plan is that two pairs of limbs develop at
      specific positions along the head-to-tail axis. However, the potential to form
      limbs in chick embryos is more widespread. This could have implications for
      understanding the basis of limb abnormalities. Here we extend the analysis to
      mouse embryos and examine systematically the potential of tissues in different
      regions outside the limbs to contribute to limb structures. We show that the
      ability of ectoderm to form an apical ridge in response to FGF4 in both mouse and
      chick embryos exists throughout the flank as does ability of mesenchyme to
      provide a polarizing region signal. In addition, neck tissue has weak polarizing
      activity. We show, in chick embryos, that polarizing activity of tissues
      correlates with the ability either to express Shh or to induce Shh expression. We
      also show that cells from chick tail can give rise to limb structures. Taken
      together these observations suggest that naturally occurring polydactyly could
      involve recruitment of cells from regions adjacent to the limb buds. We show that
      cells from neck, flank and tail can migrate into limb buds in response to FGF4,
      which mimics extension of the apical ectodermal ridge. Furthermore, when we apply
      simultaneously a polarizing signal and a limb induction signal to early chick
      flank, this leads to limb duplications.

PMID- 10952901
TI  - Positional cues specify and maintain aleurone cell fate in maize endosperm
      development.
AB  - A genetic analysis of maize aleurone development was conducted. Cell lineage was
      examined by simultaneously marking cells with C1 for anthocyanin pigmentation in
      the aleurone and wx1 for amylose synthesis in the starchy endosperm. The aleurone
      and starchy endosperm share a common lineage throughout development indicating
      that positional cues specify aleurone fate. Mutants in dek1 block aleurone
      formation at an early stage and cause peripheral endosperm cells to develop as
      starchy endosperm. Revertant sectors of a transposon-induced dek1 allele showed
      that peripheral endosperm cells remain competent to differentiate as aleurone
      cells until late in development. Ds-induced chromosome breakage was used to
      generate Dek1 loss-of-function sectors. Events occurring until late development
      caused aleurone cells to switch fate to starchy endosperm indicating that cell
      fate is not fixed. Thus, positional cues are required to specify and maintain
      aleurone fate and Dek1 function is required to respond to these cues. An analysis
      of additional mutants that disrupt aleurone differentiation suggests a hierarchy
      of gene functions to specify aleurone cell fate and then control aleurone
      differentiation. These mutants disrupt aleurone differentiation in reproducible
      patterns suggesting a relationship to endosperm pattern formation.

PMID- 10952900
TI  - Cap 'n' collar B cooperates with a small Maf subunit to specify pharyngeal
      development and suppress deformed homeotic function in the Drosophila head.
AB  - The basic-leucine zipper protein Cap 'n' collar B (CncB) suppresses the segmental
      identity function of the Hox gene Deformed (Dfd) in the mandibular segment of
      Drosophila embryos. CncB is also required for proper development of intercalary,
      labral and mandibular structures. In this study, we provide evidence that the
      CncB-mediated suppression of Dfd requires the Drosophila homolog of the mammalian
      small Maf proteins, Maf-S, and that the suppression occurs even in the presence
      of high amounts of Dfd protein. Interestingly, the CncB/Maf-S suppressive effect
      can be partially reversed by overexpression of Homothorax (Hth), suggesting that
      Hth and Extradenticle proteins antagonize the effects of CncB/Maf-S on Dfd
      function in the mandibular segment. In embryos, multimers of simple CncB/Maf-S
      heterodimer sites are transcriptionally activated in response to CncB, and in
      tissue culture cells the amino-terminal domain of CncB acts as a strong
      transcriptional activation domain. There are no good matches to CncB/Maf binding
      consensus sites in the known elements that are activated in response to Dfd and
      repressed in a CncB-dependent fashion. This suggests that some of the suppressive
      effect of CncB/Maf-S proteins on Dfd protein function might be exerted
      indirectly, while some may be exerted by direct binding to as yet uncharacterized
      Dfd response elements. We also show that ectopic CncB is sufficient to transform
      ventral epidermis in the trunk into repetitive arrays of ventral pharynx. We
      compare the functions of CncB to those of its vertebrate and invertebrate
      homologs, p45 NF-E2, Nrf and Skn-1 proteins, and suggest that the pharynx
      selector function of CncB is highly conserved on some branches of the
      evolutionary tree.

PMID- 10952903
TI  - Ectopic engrailed 1 expression in the dorsal midline causes cell death, abnormal
      differentiation of circumventricular organs and errors in axonal pathfinding.
AB  - A series of gain- or loss-of-function experiments performed in different
      vertebrate species have demonstrated that the Engrailed genes play multiple roles
      during brain development. In particular, they have been implicated in the
      determination of the mid/hindbrain domain, in cell proliferation and survival, in
      neurite formation, tissue polarization and axonal pathfinding. We have analyzed
      the consequences of a local gain of En function within or adjacent to the
      endogenous expression domain in mouse and chick embryos. In WEXPZ.En1 transgenic
      mice (Danielian, P. S. and McMahon, A. P. (1996) Nature 383, 332-334) several
      genes are induced as a consequence of ectopic expression of En1 in the
      diencephalic roof (but in a pattern inconsistent with a local di- to mes
      encephalon fate change). The development of several structures with secretory
      function, generated from the dorsal neuroepithelium, is severely compromised. The
      choroid plexus, subcommissural organ and pineal gland either fail to form or are
      atrophic. These defects are preceded by an increase in cell death at the dorsal
      midline. Comparison with the phenotype of Wnt1(sw/sw) (swaying) mutants suggests
      that subcommissural organ failure is the main cause of prenatal hydrocephalus
      observed in both strains. The formation of the posterior commissure is also
      delayed, and errors in axonal pathfinding are frequent. In chick, ectopic
      expression of En by in ovo electroporation, affects growth and differentiation of
      the choroid plexus.

PMID- 10952902
TI  - Mutations in cye-1, a Caenorhabditis elegans cyclin E homolog, reveal
      coordination between cell-cycle control and vulval development.
AB  - We have identified strong loss-of-function mutations in the C. elegans cyclin E
      gene, cye-1. Mutations in cye-1 lead to the underproliferation of many
      postembryonic blast lineages as well as defects in fertility and gut-cell
      endoreduplication. In addition, cye-1 is required maternally, but not zygotically
      for embryonic development. Our analysis of vulval development in cye-1 mutants
      suggests that a timing mechanism may control the onset of vulval cell terminal
      differentiation: once induced, these cells appear to differentiate after a set
      amount of time, rather than a specific number of division cycles. cye-1 mutants
      also show an increase in the percentage of vulval precursor cells (VPCs) that
      adopt vulval cell fates, indicating that cell-cycle length can play a role in the
      proper patterning of vulval cells. By analyzing cul-1 mutants, we further
      demonstrate that vulval cell terminal differentiation can be uncoupled from
      associated changes in vulval cell division planes.

PMID- 10952905
TI  - Editor's preface

PMID- 10952906
TI  - Human Y chromosome, sex determination, and spermatogenesis- a feminist view.
AB  - In this review I want to argue that, far from being a macho entity with an all
      powerful role in male development, the human Y chromosome is a "wimp." It is
      merely a relic of the X chromosome, and most or all of the genes it bears
      including the genes that determine sex and control spermatogenesis-are relics of
      genes on the X chromosome that have other functions altogether.

PMID- 10952904
TI  - The transcription factor dHAND is a downstream effector of BMPs in sympathetic
      neuron specification.
AB  - The dHAND basic helix-loop-helix transcription factor is expressed in neurons of
      sympathetic ganglia and has previously been shown to induce the differentiation
      of catecholaminergic neurons in avian neural crest cultures. We now demonstrate
      that dHAND expression is sufficient to elicit the generation of ectopic
      sympathetic neurons in vivo. The expression of the dHAND gene is controlled by
      bone morphogenetic proteins (BMPs), as suggested by BMP4 overexpression in vivo
      and in vitro, and by noggin-mediated inhibition of BMP function in vivo. The
      timing of dHAND expression in sympathetic ganglion primordia, together with the
      induction of dHAND expression in response to Phox2b implicate a role for dHAND as
      transcriptional regulator downstream of Phox2b in BMP-induced sympathetic neuron
      differentiation.

PMID- 10952907
TI  - Effects of preactivation of ooplasts or synchronization of blastomere nuclei in
      G1 on preimplantation development of rabbit serial nuclear transfer embryos.
AB  - Blastomeres from eight-cell-stage rabbit embryos have been fused with enucleated
      metaphase II oocytes (ooplasts) or with ooplasts that were preactivated before
      fusion. Preactivation of ooplasts before nuclear transfer (NT) raises the rate of
      preimplantation development from 15% to 56%, which remains elevated in the next
      series of NT (48.6% and 47.2% in the second and third rounds, respectively).
      Transfer of eight-cell embryos from the third round to the recipient resulted in
      the birth of normal young. Synchronization of blastomere nuclei in the G1 phase
      with nocodazole before fusion results in 42% morula/blastocyst formation.
      However, in the second generation of NT embryos, the yield drops to as low as
      17%, indicating deleterious effects of the second nocodazole treatment on
      blastomeres. The calculated number of clones per one round of cloning was 4.5,
      3.9, and 3.8 in subsequent series; the highest number of morulae and blastocysts
      that developed from individual donor embryos after three rounds were 26 and 27,
      respectively.

PMID- 10952908
TI  - IL-15 expression at human endometrium and decidua.
AB  - A large number of natural killer (NK) cells appear in human uterine mucosa during
      the secretory phase and first trimester pregnancy. We investigated the expression
      of interleukin (IL)-15, a possible stimulator for these NK cells, in human
      endometrium and first trimester decidua. Semiquantitative reverse transcriptase
      polymerase chain reaction revealed that IL-15 mRNA expression was stronger during
      the secretory phase and first trimester pregnancy than during the proliferative
      phase. Immunohistochemistry revealed that immunoreactivity for anti-IL-15 was
      higher during the secretory phase than it was during the proliferative phase.
      This was prominent in the perivascular stromal cells around invading spiral
      arteries during the mid- to late-secretory phase. In first trimester decidua,
      endothelial cells were also stained as strongly as stromal cells. A membrane
      bound IL-15 molecule was detected on the surface of first trimester decidual
      cells by flow cytometry. Progesterone stimulated the release of soluble IL-15 in
      the supernatant of cultured decidual cells. These results suggest that IL-15
      expression in human uterine mucosa corresponds to the fluctuation of uterine NK
      cells and that its production is hormonally controlled, especially by
      progesterone.

PMID- 10952909
TI  - Biosynthesis, processing, and subcellular localization of rat spermbeta-D
      galactosidase.
AB  - During spermatogenesis, spermatids synthesize constituent proteins present in
      mature spermatozoa; however, little information exists on the molecular processes
      involved. In previous studies, this laboratory reported the characterization of
      rat sperm beta-D-galactosidase. In this paper, we report the localization of this
      enzyme along with its biosynthesis and processing. An antibody against rat
      luminal fluid beta-D-galactosidase was used to immunolocalize the enzyme in the
      testis and in epididymal spermatozoa. We found that beta-D-galactosidase is
      localized within the acrosomal cap of spermatids and in the acrosome and
      cytoplasmic droplet of epididymal spermatozoa. A combination of germ cell
      radiolabeling, immunoprecipitation, SDS-PAGE, and autoradiography revealed that
      spermatids produce two forms of beta-D-galactosidase, 90 and 88 kDa. During pulse
      chase analysis, a 56-kDa form appeared. Treatment of beta-D-galactosidase
      immunoprecipitates from testicular spermatozoa with N-glycanase or Endo H
      revealed that both the 90- and 88-kDa forms become a 70-kDa polypeptide on SDS
      PAGE. Since Endo H or N-glycanase treatment provided similar results, the
      presence of extensive N-linked high mannose/hybrid-type glycans on these proteins
      is indicated. Treatment of the 56-kDa form of beta-D-galactosidase with Endo H or
      N-glycanase resulted in the appearance of 52- and 50-kDa forms, respectively.
      This result suggests that the 56-kDa form contains N-linked high mannose/hybrid
      as well as complex oligosaccharides. During epididymal maturation, the 90-kDa
      form of beta-D-galactosidase persists in caput epididymal spermatozoa and is
      gradually converted to a major 74-kDa form in cauda spermatozoa. In addition to
      the 90- to 74-kDa forms, cauda spermatozoa show a 56- to 52-kDa form on Western
      immunoblots. Since only the high-molecular weight forms of beta-D-galactosidase
      are present on immunoblots of isolated sperm heads, we suggest that they are
      acrosomal in origin and that the 56-kDa form, which is processed to 52 kDa in
      cauda spermatozoa, is associated with the cytoplasmic droplet.

PMID- 10952910
TI  - Collagen studies in late pregnant relaxin null mice.
AB  - The relaxin knockout (rlx -/-) mouse was used to assess the effect, during
      pregnancy, of relaxin with regard to water, collagen content, growth, and
      morphology of the nipple (N), vagina (V), uterus, cervix (C), pubic symphysis
      (PS), and mammary gland (MG). The results presented here indicate that during
      pregnancy, relaxin increases the growth of the N, C, V, and PS. Large increases
      in water content in the PS (20%) occurred in pregnant (Day 18.5) wild-type (rlx
      +/+) mice but not in rlx -/- animals. This indicates that in the PS, relaxin
      might increase the concentration of a water-retaining extracellular matrix
      component (hyaluronate). In the pregnant rlx +/+ mouse, collagen content
      decreased significantly in the N and V but not in other tissues. There were no
      significant changes in the rlx -/- mouse. This contrasts with findings in the
      rat, in which relaxin has been found to cause decreases in collagen
      concentrations in the V, C, and PS. Histological analysis showed that the
      collagen stain was more condensed in the tissues (V, C, PS, N, and MG) of rlx -/-
      mice than in those of rlx +/+ mice. This phenomenon indicates that the failure of
      collagen degradation and lack of growth in the N underlie the inability of the
      rlx -/- mice to feed their young, as reported previously. Vaginal and cervical
      luminal epithelia, which proliferated markedly in the rlx +/+ pregnant mice,
      remained relatively atrophic in the rlx -/- mice. As proliferation and
      differentiation of uterine and vaginal epithelia are thought to be induced by a
      paracrine stromal factor that acts upon estrogen stimulation, our results
      indicate that relaxin may be this paracrine factor.

PMID- 10952911
TI  - Expression of penile neuronal nitric oxide synthase variants in the rat and mouse
      penile nerves.
AB  - Penile erection is mediated by nitric oxide (NO) synthesized by the neuronal
      nitric oxide synthase (nNOS). In the rat penis, the main nNOS mRNA variant,
      PnNOS, differs from cerebellar nNOS (CnNOS) by a 102 base pair insert encoding a
      34-amino acid sequence. In the mouse, two nNOS mRNAs have been identified:
      nNOSalpha, encoding a 155-kDa protein, and an exon 2-deletion variant, nNOSbeta,
      encoding a 135-kDa protein that lacks a domain where a protein inhibitor of nNOS
      (PIN) binds. We wished to determine whether PnNOSalpha and beta are expressed in
      the rat penis and are located in the nerves and whether the beta form persists in
      the potent nNOS knock-out mouse (nNOS( big up tri, open big up tri, open)). A
      PnNOS antibody against the insert common to both PnNOSalpha and beta detected the
      expected 155-kDa protein in PnNOSalpha-transfected cells. This antibody, and the
      one common to PnNOS/CnNOS, showed (on Western blots) the 155- and 135-kDa nNOS
      variants in rat penile tissue during development and aging. PnNOSalpha mRNA and
      its subvariants were found as the main nNOS in the penile corpora, the cavernosal
      nerve, and the pelvic ganglia, with lower levels of PnNOSbeta mRNA. In tissue
      sections, PnNOS protein was immunodetected in the penile nerve endings in the rat
      and in the nNOS wild-type and nNOS( big up tri, open big up tri, open) mice. An
      antibody against the sequence encoded by exon 2 did not react (on Western blots)
      with the 135-kDa band, which confirms that this protein is the beta form. In
      conclusion, both PnNOSalpha and beta are expressed in the rat penis at all ages
      and are located in the nerves. The beta form may allow nitric oxide synthesis
      during erection to be partially insensitive to PIN. The residual expression of
      PnNOS, and possibly CnNOS, in the penis of the nNOS( big up tri, open big up tri,
      open) mouse occurs through transcription of the beta mRNA, and this may explain
      the retention of erectile function when the expression of nNOSalpha is disrupted.

PMID- 10952912
TI  - Maturation/M-phase promoting factor: a regulator of aging in porcine oocytes.
AB  - Deterioration in the quality of mammalian oocytes during the metaphase-II arrest
      period is well known as "oocyte aging." Oocytes in which aging has occurred are
      called aged oocytes, and these oocytes show enhanced activation and higher
      fragmentation rates after parthenogenetic activation. Previously we showed that
      porcine aged oocytes had low maturation/M-phase promoting factor (MPF) activity,
      and we suggested that this low MPF activity contributed at least in part to the
      aging phenomena. In the present study, we examined the relationship between MPF
      activity and these aging phenomena by artificially regulating MPF activity in
      porcine metaphase-II-arrested oocytes. Since we have shown recently that aged
      porcine oocytes contain abundant phosphorylated inactive MPF, so-called pre-MPF,
      we used vanadate and caffeine, which affect the phosphorylation status of MPF, to
      regulate MPF activity. Incubation of 48-h-matured oocytes with vanadate for 1 h
      increased the phosphorylation of MPF and decreased MPF activity. The
      parthenogenetic activation and fragmentation rates were significantly increased
      compared with those of control oocytes. Conversely, treatment of 72-h-cultured
      aged oocytes with caffeine (last 10 h of culture) decreased the level of pre-MPF
      and elevated MPF activity. These oocytes revealed significantly lower
      parthenogenetic activation rates and a lower percentage of fragmentation than did
      untreated aged oocytes. These results indicate that not only the increased
      ability for parthenogenetic activation but also the increased fragmentation rate
      observed in porcine aged oocytes may be attributable in part to the gradual
      decrease in MPF activity during prolonged culture. Control of MPF phosphorylation
      with these agents may allow for some degree of manipulation of oocyte aging.

PMID- 10952913
TI  - Dynamic changes of cumulus-oocyte cell communication during in vitro maturation
      of porcine oocytes.
AB  - Oocyte maturation is a key issue of current animal biotechnology. This study was
      designed to examine the morphodynamics of the cumulus-oocyte association during
      oocyte maturation. Porcine cumulus-oocyte complexes were recovered from
      slaughterhouse ovaries; matured in vitro for 0, 24, 36, and 44 h; and evaluated
      by scanning electron microscopy either combined or not combined with the osmium
      dimethyl sulfoxide-osmium maceration (ODO) method. The cytoskeleton distribution
      was also observed by fluorescence staining. Prior to maturation culture (0 h),
      the spherical cumulus cells were tightly clustered around the oocyte, with narrow
      intercellular spaces. They showed active secretion at 36 h and were fully
      expanded at 44 h of culture. The ODO methods revealed that the cumulus cells
      projected numerous long and thin transzonal projections at 0 h, but these were
      largely disconnected at 44 h. The outer surface of the zona pellucida showed a
      meshwork surface regardless of time of incubation, whereas the inner surface
      changed from a fine fibrous surface to a spongy surface that was coated with
      mucin. The vitelline surface changed from a sparse distribution of short
      microvilli (MV) to a dense distribution of well-developed MV. Fluorescence
      staining showed that the cumulus cell projections consisted mainly of
      microfilaments, which were abundant at the germinal vesicle and metaphase-I (M-I)
      stages (0-24 h) but which were decreased in number at the M-II stage (36-44 h).
      We conclude that the cumulus-oocyte transzonal projections became disconnected
      between the M-I and M-II stages as a result of cumulus expansion. The cumulus
      cumulus communications, however, remained intact at these stages, although the
      biological functions of these communications were not clear.

PMID- 10952914
TI  - Alteration of follicle-stimulating hormone and testosterone regulation of
      messenger ribonucleic acid for Sertoli cell proteins in the rat during the acute
      phase of spinal cord injury.
AB  - The detrimental effects of spinal cord injury (SCI) on spermatogenesis in the rat
      can be attenuated by exogenous testosterone (T) but enhanced by exogenous
      follicle-stimulating hormone (FSH). These results suggest that T-dependent
      cellular events may be involved in testicular injury after SCI and that such
      events may be associated with modification of FSH effects on Sertoli cell
      function. The current study compared the responses of Sertoli cells to exogenous
      T and FSH after SCI or sham surgery using steady-state levels of Sertoli cell
      protein mRNA transcripts as markers of responsiveness. Rats underwent sham
      surgery or SCI and then were treated for 7 or 14 days with T-filled silastic
      capsules (2 x 5 cm) and/or daily injections of 0.1 units of porcine FSH. Vehicle
      treated control rats received 5-cm empty capsules and daily injections of saline
      vehicle. Two weeks after sham surgery, levels of mRNA for the androgen receptor
      (AR), FSH receptor (FSHR), androgen-binding protein (ABP), or sulfated
      glycoprotein (SGP)-2 in the testis were unaffected by T or FSH alone.
      Testosterone alone, however, significantly decreased transferrin (Trf) mRNA
      levels in the testis (P: < 0.01). The combination of T and FSH treatments
      resulted in significant decreases in levels of the above transcripts (P: < 0.05;
      P: < 0.01). Seven days after SCI, the testes of vehicle-treated SCI rats had
      higher levels of AR and SGP-2 mRNA than did those of sham control rats (P: <
      0.01); such effects were transient and disappeared by Day 14 post-SCI.
      Testosterone treatment of SCI rats for 7 days resulted in decreases in mRNA
      levels for AR and Trf in the testes (P: < 0.01) but increased testicular levels
      of mRNAs for FSHR and SGP-2 in SCI rats. Follicle-stimulating hormone treatment
      for 7 days prevented the increase in AR mRNA that was seen in the testis of
      untreated SCI rats and increased levels of ABP and SGP-2 mRNAs in SCI rats (P: <
      0.01). Follicle-stimulating hormone treatment of SCI rats did not affect FSHR
      mRNA levels by itself, but it blocked the stimulatory effect of T on FSHR and SGP
      2 mRNAs. Fourteen days after SCI, testicular AR mRNA levels were not affected by
      T alone, but they increased in those rats that received FSH with or without
      concurrent T treatments (P: < 0.05). In contrast to their effects in sham control
      rats, T or FSH alone or in combination resulted in significant increases in
      testicular levels of ABP, SGP-2, and FSHR mRNAs (P: < 0.05). At this time, Trf
      mRNA in the testis of SCI rats was also suppressed by T (P: < 0.05), as it did in
      sham control rats, but Trf mRNA was increased by the FSH (P: < 0.01) that had
      inhibited this transcript in the testes of sham control rats. The effects of FSH
      on the Sertoli cell transcripts in SCI rats were either attenuated or blocked
      when T was given concurrently. In addition, testicular and serum T levels in
      those SCI rats that received FSH (alone or in combination with T) for 14 days
      were significantly increased, an effect that was not seen after sham surgery.
      These findings demonstrate that hormonal regulation of both Sertoli and Leydig
      cells was altered during the acute phase of SCI. Such changes may modify the
      functions of both cell types, thereby affecting the endocrine and/or paracrine
      microenvironment within the seminiferous epithelium. These effects could impair
      the functional capacity of Sertoli cells and contribute to impairment of
      spermatogenesis after SCI.

PMID- 10952915
TI  - Rapid androgen actions on calcium signaling in rat sertoli cells and two human
      prostatic cell lines: similar biphasic responses between 1 picomolar and 100
      nanomolar concentrations.
AB  - Androgen-induced calcium fluxes and gap junctional intercellular communication
      (GJIC) were studied in three different cell types. A transient (2-3 min duration)
      increase in intracellular calcium levels was observed within 20-30 sec of
      androgen addition, which was followed by a plateau phase with steroid
      concentrations higher than 1 nM. The kinetics of the calcium responses were
      similar in immature rat Sertoli cells, which contain normal nuclear receptors;
      the human prostatic tumor cell line, LNCaP, which contains a mutated nuclear
      receptor; and the human prostatic cell line, PC3, which does not contain a
      nuclear receptor. The human A431 tumor cell line did not respond to androgens.
      Concentrations of testosterone and the synthetic androgen, R1881, between 1-1000
      pM induced transient calcium increases with ED(50) values near 1 pM and 1 nM,
      whereas dihydrotestosterone (DHT) was not active at these concentrations. At
      concentrations higher than 1 nM, testosterone, R1881, and DHT were equipotent in
      stimulating an increase in calcium that lasted for more than 10 min, with ED(50)
      values between 5 and 20 nM. Testosterone covalently bound to albumin was also
      active, whereas 11 related androstane compounds as well as progesterone and
      estradiol-17beta were inactive at 1000 nM. The calcium response induced by the
      three androgens (10 nM) was abolished in all cell types by hydroxyflutamide (1000
      nM) and finasteride (1000 nM), but not by cyproterone acetate (1000 nM). The
      calcium response was also abolished in the absence of extracellular calcium and
      strongly inhibited by the presence of verapamil. Exposure of the responsive cells
      to brief (150-sec) pulses of androgens generated calcium responses that were
      similar to those after continuous exposure. After exposure of Sertoli cells for
      only 30 sec to 100 nM testosterone, the calcium response lasted for at least 50
      min. Although nuclear binding of androgens could be demonstrated, there was no
      evidence for tight binding to the plasma membrane under similar conditions. When
      protein synthesis was inhibited, an enhancement of GJIC between rat Sertoli
      cells, but not between LNCaP cells or PC3 cells, was observed within 15 min of
      the addition of 10 nM testosterone. Because nuclear androgens are not present in
      PC3 cells and many functional properties of the responsive system are different
      from the nuclear receptor in all three cell types, we postulate the existence of
      an alternative cell surface receptor system with biphasic response
      characteristics (high and low affinity). The calcium signals are probably coupled
      to the regulation of gap junctional efficiency between Sertoli cells. The low
      affinity receptors may convey complementary androgen signals at elevated local
      levels such as in the testis, when nuclear receptors are (over)saturated.

PMID- 10952916
TI  - Calcium homeostatic pathways change with gestation in human myometrium.
AB  - A rise in intracellular calcium is the primary trigger for contractile activity
      in pregnant human myometrium. It is hypothesized that key proteins involved in
      myometrial calcium homeostasis are gestationally regulated and play an important
      role in the preparation for labor. The aims of the study were to investigate the
      role of sarcoplasmic reticulum Ca ATPases (SERCAs) in regulating spontaneous
      contractile activity in myometrium, and to determine the expression of SERCA
      isoforms 2a and 2b, and the plasma membrane Ca ATPase (PMCA), at term and during
      labor. Western blot analysis demonstrated that the expression of SERCA 2a and 2b
      significantly increased in myometrium of women in labor compared with those not
      in labor. The augmentation of contractile activity in laboring myometrium in the
      presence of a SERCA 2 inhibitor, cyclopiazonic acid (CPA), demonstrated the
      functional significance of this observation. It is interesting that the
      application of CPA in the presence of a calcium-activated potassium channel
      inhibitor to term nonlabor myometrium mimicked the response of myometrium from
      women in active labor to CPA alone. We conclude that the activity of SERCA
      isoforms becomes increasingly important in the maintenance of regular contractile
      activity during labor and may compensate for the functional loss of other calcium
      control pathways at term.

PMID- 10952917
TI  - Follicular development and atresia in the B6.Y(TIR) sex-reversed mouse ovary.
AB  - The B6.Y(TIR) mouse fails to develop normal testes despite transcription of Sry,
      the primary testis-determining gene on the Y chromosome. Consequently, B6.Y(TIR)
      fetuses with bilateral ovaries develop into apparently normal but infertile
      females. This infertility can be mainly attributed to oocyte incompatibility for
      postfertilization development. In addition, abnormality in preovulatory follicles
      and rapid loss of oocytes have been observed in XY ovaries. This study examined
      the effect of gonadotropins on follicular development and atresia in B6.Y(TIR)
      prepubertal females. The results show that untreated XY females had fewer late
      preantral follicles and their frequency of atresia was lower. No other difference
      was found when they were compared with XX females. After treatment with
      gonadotropins for 24 h, frequency of atresia decreased in both XX and XY ovaries.
      After 48 h, most preovulatory follicles in XY ovaries were nonatretic, but the
      oocytes often were denuded. Immunocytochemical staining for connexin 43 detected
      punctate foci along the oocyte plasma membrane. The density of these foci changed
      during follicular development, which was similar in XX and XY ovaries. In
      conclusion, follicular development and atresia under the control of gonadotropins
      is not influenced by defective oocytes until the preovulatory phase.

PMID- 10952918
TI  - The rat endozepine-like peptide gene is highly expressed in late haploid stages
      of male germ cell development.
AB  - The structure of the endozepine-like peptide (ELP) gene is closely related to the
      intracellular acyl-CoA binding protein (ACBP), but unlike the generalized
      distribution of the latter, it is restricted to the male germ cells of the
      testis. In the present study, a combination of nonradioactive in situ mRNA
      hybridization and immunohistochemistry was used to precisely determine the
      cellular expression patterns of ELP mRNA and protein in control and methoxyacetic
      acid (MAA)-treated rat testes. ELP transcripts are first detectable in late
      stages (step 6) of round spermatids, with transcription increasing through late
      elongating steps. Translation of the ELP mRNA is delayed, with first
      immunohistochemical staining occurring in elongated spermatids at step 16, and
      protein accumulating through step 19. ELP immunoreactivity proves to be an
      excellent marker for late spermatid stages and highlights the presumably clonal
      recovery of spermatids following MAA treatment.

PMID- 10952919
TI  - Importance of photoperiodic signal quality to entrainment of the circannual
      reproductive rhythm of the ewe.
AB  - An endogenous circannual rhythm drives the seasonal reproductive cycle of a broad
      spectrum of species. This rhythm is synchronized to the seasons (i.e., entrained)
      by photoperiod, which acts by regulating the circadian pattern of melatonin
      secretion from the pineal gland. Prior work has revealed that melatonin patterns
      secreted in spring/summer entrain the circannual rhythm of reproductive
      neuroendocrine activity in sheep, whereas secretions in winter do not. The goal
      of this study was to determine if inability of the winter-melatonin pattern to
      entrain the rhythm is due to the specific melatonin pattern secreted in winter or
      to the stage of the circannual rhythm at that time of year. Either a summer- or a
      winter-melatonin pattern was infused for 70 days into pinealectomized ewes,
      centered around the summer solstice, when an effective stimulus readily entrains
      the rhythm. The ewes were ovariectomized and treated with constant-release
      estradiol implants, and circannual cycles of reproductive neuroendocrine activity
      were monitored by serum LH concentrations. Only the summer-melatonin pattern
      entrained the circannual reproductive rhythm. The inability of the winter pattern
      to do so indicates that the mere presence of a circadian melatonin pattern, in
      itself, is insufficient for entrainment. Rather, the characteristics of the
      melatonin pattern, in particular a pattern that mimics the photoperiodic signals
      of summer, determines entrainment of the circannual rhythm of reproductive
      neuroendocrine activity in the ewe.

PMID- 10952920
TI  - Androgen control of cyclooxygenase expression in the rat epididymis.
AB  - Bradykinin and a number of peptide hormones such as angiotensin, endothelin, and
      vasopressin stimulate anion secretion in rat epididymis via local formation of
      PGE(2). These effects are mediated by cyclooxygenase (COX)-1 isozyme. The present
      study was undertaken to assess the androgen control of COX expression in the
      epididymis. Adult male Sprague-Dawley rats were bilaterally castrated through a
      scrotal route. Reverse transcription-polymerase chain reaction was used to
      measure COX-1 and COX-2 mRNAs in the epididymis in normal and castrated rats.
      Anion secretion in epithelia grown from the epididymides of these rats was
      studied by the short-circuit current technique. In normal rats, COX-1 and COX-2
      mRNAs were detected in the intact epididymis. Elimination of spermatozoa by the
      technique of efferent duct ligation or flushing out spermatozoa did not affect
      the expression of either enzyme in the epididymis, indicating that the
      epithelium, but not spermatozoa, expressed the enzymes. Castration caused a time
      dependent decrease in expression of COX-1 and COX-2 mRNAs, which were partially
      restored upon testosterone replacement. In epithelia cultured from castrated
      rats, there was a complete loss of bradykinin-induced anion secretion. This
      effect was reversible upon testosterone replacement. Although epithelia from
      castrated rats did not respond to bradykinin, they could respond to cAMP,
      forskolin, and PGE(2) with only 20% loss of response magnitude when compared with
      epithelia from normal rats. These results suggest that the expression of COX-1
      and COX-2 are dependent on androgen. The loss of COX-1 expression after
      castration correlates with the specific loss of anion secretion induced by
      bradykinin and possibly other hormones.

PMID- 10952921
TI  - Divergence in murine myometrium spontaneous and oxytocin-stimulated contractile
      responses to serine/threonine protein phosphatase-1 inhibition.
AB  - Reversible phosphorylation is essential in regulating uterine contractions.
      Identification, characterization, and functional understanding of myometrium
      protein phosphatase(s) are lacking. Okadaic acid (OA), which inhibits protein
      phosphatase-1 (PP1) and PP2A, has been shown to alter uterine contractions.
      Experiments were conducted to determine the 1) identity of the myometrial OA
      sensitive PP, 2) influence of OA on spontaneous and oxytocin (OT)-stimulated
      myometrial contractions, and 3) expression of uterine PPs during sexual
      development. Western blot analysis indicated the presence of PP1(alpha) and PP2A
      in immature and mature mice. As determined by immunohistochemistry, gonadotropin
      stimulated adult mouse uteri contain PP1(alpha) in longitudinal and circular
      myometrial layers and endometrial epithelium. Conversely, PP2A was localized to
      the endometrial stroma. Cumulative addition of OA (n = 9; 10, 100, 250, 500, 1000
      nM) did not significantly alter spontaneous contractions of mouse uterine horns
      in comparison to vehicle-treated controls (n = 9). By the end of the test period
      OA- and vehicle-treated uteri displayed a comparable decline in uterine
      contractions to 79.2% and 63.7%, respectively, of basal contractile activity.
      Pretreatment of uterine tissue with OA (1 microM; n = 7) significantly reduced
      contractile response to increasing concentrations of OT (8, 16, 32, 64 nM) in
      comparison to vehicle pretreatment (dimethyl sulfoxide; n = 7). At the end of the
      OT-administration period, contractile activity was 160.4% and 67.3% of basal
      contractile activity for vehicle (no OA) and OA-pretreated groups, respectively.
      During the early prepubertal period PP1(alpha) was expressed in longitudinal
      myometrium and absent in circular myometrium; whereas, during the transition to
      sexual maturity PP1(alpha) was observed in both the longitudinal and circular
      myometrium. In summary, these studies have indicated 1) that PP1 is the primary
      myometrial OA-sensitive PP; 2) that inhibition of PP1 had no effect on
      spontaneous contractions, whereas it markedly inhibited OT-stimulated uterine
      contractions; and 3) that PP1 is differentially expressed in the circular and
      longitudinal myometrium in relation to sexual development.

PMID- 10952922
TI  - Expression and action of transforming growth factor alpha in normal ovarian
      surface epithelium and ovarian cancer.
AB  - Greater than 95% of ovarian cancers originate in the epithelial cells on the
      surface of the ovary. The current study investigates the expression and action of
      transforming growth factor alpha (TGFalpha) in ovarian surface epithelium (OSE)
      and the underlying stroma in both normal and tumorigenic ovarian tissues. Normal
      bovine ovaries are used in the current study as a model system to investigate
      normal OSE functions. Transforming growth factor alpha and its receptor, the
      epidermal growth factor receptor (EGFR), were detected in the OSE from normal
      ovaries by immunocytochemistry (ICC). Ovarian stromal tissue also contained
      reduced but positive TGFalpha and EGFR immunostaining. To examine TGFalpha and
      EGFR gene expression, RNA was collected from normal bovine OSE and ovarian
      stromal cells. The TGFalpha and EGFR transcripts were detected in both fresh and
      cultured OSE and stromal cells by a sensitive quantitative reverse transcription
      polymerase chain reaction (QRT-PCR) assay. Transforming growth factor alpha gene
      expression was found to be high in freshly isolated OSE, but low in freshly
      isolated stroma. In contrast, EGFR expression was higher in the stroma compared
      to the OSE. Both the ICC and QRT-PCR indicate that normal OSE express high levels
      of TGFalpha in vivo and in vitro. In vitro, normal ovarian stromal cells develop
      the capacity to express high levels of EGFR. Human ovarian tumors from stage II,
      stage III, and stage IV ovarian cancer cases were found to express TGFalpha and
      EGFR protein in the epithelial cell component of the tumor by ICC analysis. The
      stromal cell component of human ovarian tumors contained little or no
      TGFalpha/EGFR immunostaining. Observations suggest that tumor progression may in
      part require autocrine stimulation of the epithelia. Transforming growth factor
      alpha was found to stimulate the growth of normal bovine OSE and stroma cells to
      the same level as epidermal growth factor. Two ovarian cancer cell lines, SKOV3
      and OCC1, were also stimulated to proliferate in response to TGFalpha.
      Transforming growth factor alpha was also found to stimulate the expression of
      two growth factors previously shown to be produced by OSE. Transforming growth
      factor alpha stimulates both kit ligand/stem cell factor and keratinocyte growth
      factor production by OSE. The effect of hormones on TGFalpha and EGFR expression
      by the OSE was also examined. Human chorionic gonadotropin stimulated TGFalpha
      expression, but not FSH. Both hCG and FSH stimulated EGFR expression by OSE.
      Combined observations suggest a role of systemic hormones and a locally produced
      growth factor, TGFalpha, in OSE biology. Insight is also provided into how the
      OSE may develop abnormal growth characteristics involved in the onset and
      progression of ovarian cancer.

PMID- 10952923
TI  - Developmental expression and distribution of N- and E-cadherin in the rat ovary.
AB  - The calcium-dependent cell adhesion molecules, cadherins, regulate intercellular
      junction formation, cell sorting, and the establishment of cell polarity. Their
      important role in tissue remodeling suggests an involvement in ovarian cellular
      rearrangements throughout postnatal development. The ovary has a complex
      topology, and the ovarian follicle undergoes significant cellular rearrangements
      during its development. Cadherins have been detected previously in whole ovaries
      and in ovarian cells and cell lines with some immunolocalization in fetal and
      adult ovaries. This study examines the expression and localization of N- and E
      cadherin throughout prepubertal ovarian and follicular development in the rat. We
      analyzed ovarian cadherin expression in rats from Day 19-20 of gestation to 25
      days postpartum, during which follicle formation and folliculogenesis are the
      dominant ovarian events. Reverse transcriptase polymerase chain reaction detected
      N- and E-cadherin mRNA expression in the ovaries at all the ages examined.
      Semiquantification of Western blots of whole ovary extracts confirmed the
      presence of ovarian N- and E-cadherin protein at all ages with both showing peak
      expression at 7 days of age. Immunostaining revealed N- and E-cadherin expression
      in follicular and extrafollicular cell types, but only E-cadherin showed follicle
      stage-dependent expression. The changes in cadherin expression, concurrent with
      ovarian growth and folliculogenesis, suggest a function for cadherins in the
      morphological and functional development of the prepubertal rat ovary.

PMID- 10952924
TI  - Protection of porcine oocytes against apoptotic cell death caused by oxidative
      stress during In vitro maturation: role of cumulus cells.
AB  - The present study was conducted to examine the protective effect of cumulus cells
      on oocyte damage caused by reactive oxygen species (ROS), generated by the
      hypoxanthine-xanthine oxidase (XOD) system, during in vitro maturation of porcine
      oocytes. Cumulus-oocyte complexes (COCs) and cumulus-denuded oocytes (DOs) were
      cultured for 44 h in NCSU37 supplemented with cysteine, gonadotropins, 10%
      porcine follicular fluid, and hypoxanthine in the presence or absence of XOD. DNA
      cleavage and damage were analyzed using the terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL) method and single cell microgel
      electrophoresis (comet) assay, respectively, and caspase-3 activity and
      glutathione (GSH) content were measured in each experimental group. Exposure of
      DOs to ROS resulted in meiotic arrest and the increase of degenerated oocytes.
      These degenerated DOs underwent apoptosis, as shown by the TUNEL-positive
      reaction within their germinal vesicles and the activation of caspase-3. The
      length of DNA migration in DOs treated with XOD was significantly longer than
      that of untreated DOs (P: < 0.05). However, irreparable cell damage caused by ROS
      was not observed in COCs, and no difference was observed in the caspase-3
      activity of both COCs treated with and without XOD. A significantly (P: < 0.05)
      high level of GSH was found in COCs after 44 h of culture, compared with that of
      oocytes freshly isolated from their follicles, whereas GSH content in DOs
      markedly decreased after treatment with or without XOD. These findings suggest
      that cumulus cells have a critical role in protecting oocytes against oxidative
      stress-induced apoptosis through the enhancement of GSH content in oocytes.

PMID- 10952925
TI  - Identification of potential intrafollicular factors involved in selection of
      dominant follicles in heifers.
AB  - A surgical procedure to aspirate follicular fluid concurrently from individual
      follicles from the same heifer was validated and used to determine if
      intrafollicular amounts of estradiol, progesterone, inhibins, activin-A,
      follistatins, and insulin-like growth factor binding proteins (IGFBP) differed
      for the future dominant compared with subordinate follicles during selection of
      the first wave dominant follicle. Heifers were subjected to surgery and
      aspiration of follicular fluid from the two or three largest follicles on Day 3
      of the estrous cycle (approximately 1.5 days after emergence). Ultrasound was
      used to determine the fate of each aspirated follicle after surgery. At
      aspiration, diameter of the future dominant and largest subordinate follicle was
      similar in heifers. However, estradiol was higher, whereas IGFBP-4 was lower in
      the future dominant compared with the largest or next largest subordinate
      follicles. Also, the future dominant follicle in most cohorts had the highest
      estradiol and lowest IGFBP-4 compared with future subordinate follicles. We
      concluded that: IGFBP-4 and estradiol may have key roles in determining the
      physiological fate of follicles during selection of the first wave dominant
      follicle in heifers, and that both are reliable markers to predict which follicle
      in a growing cohort of 5- to 8.5-mm follicles becomes dominant.

PMID- 10952926
TI  - Modulation of the action of chorionic gonadotropin in the baboon (Papio anubis)
      uterus by a progesterone receptor antagonist (ZK 137. 316).
AB  - Signals from the developing mammalian blastocyst rescue the corpus luteum (CL)
      and modulate the uterine environment in preparation for implantation and early
      pregnancy. Our previous studies demonstrated that both short- and long-term
      administration of chorionic gonadotropin (CG) markedly alters the morphology and
      the biochemical activity of the receptive endometrium. Because the effects of CG
      were superimposed on a progesterone-primed endometrium, this study was undertaken
      to determine if the inhibition of progesterone action by progesterone receptor
      antagonists (PRa) in intact and ovariectomized baboons would alter the action of
      CG on the endometrium at the time of uterine receptivity. In the short-term hCG
      treated baboons, the PRa reduced the epithelial plaque reaction, completely
      inhibited alpha-smooth muscle actin (alphaSMA) expression in stromal fibroblasts,
      and induced the reappearance of the progesterone (PR) and estrogen (ERalpha)
      receptors in epithelial cells. However, this treatment protocol had no effect on
      the expression of glycodelin in the glandular epithelium. In contrast, glycodelin
      expression in addition to alphaSMA was suppressed in the ovariectomized animals.
      In the long-term hCG-treated baboons, the PRa had a similar effect on both
      alphaSMA, PR, and ER. In addition, this treatment also resulted in an inhibition
      of glycodelin expression in the glandular epithelium. These results indicate that
      blocking the action of progesterone on the endometrium even for a short period of
      time has a profound effect on the hCG-induced response in stromal fibroblasts. In
      contrast, for the diminution of glandular epithelial function in the presence of
      an ovary requires prolonged inhibition of progesterone action, suggesting a
      potential paracrine effect on the endometrium from the CL in response to hCG.

PMID- 10952927
TI  - Characterization and distribution of gonadotrophs in the pars distalis and pars
      tuberalis of the equine pituitary gland during the estrous cycle and seasonal
      anestrus.
AB  - Little is known about the neuroendocrine control of fertility in the horse. In
      this species, unusual features characterize the normal estrous cycle such as a
      prolonged preovulatory LH surge during the follicular phase and a distinctive FSH
      surge during the midluteal phase. This study investigated the distribution and
      hormonal identity of gonadotrophs in the pars distalis (PD) and pars tuberalis
      (PT) of the equine pituitary gland as possible morphological bases for the
      referred unusual endocrine characteristics. In addition, the proportion of
      gonadotrophs in relation to other pituitary cell types during both the estrous
      cycle and anestrus were investigated. Pituitary glands were collected from
      sexually active (n = 5) and seasonally anestrous (n = 5) mares in November, and
      single or double immunofluorescent staining was carried out on 6-microm sections
      using monoclonal antibodies to the LHbeta or FSHbeta subunits and a polyclonal
      antibody to ovine LHbeta. Gonadotrophs were densely distributed around the pars
      intermedia in the PD and in the caudal ventral region of the PT. In addition to
      isolated cells, clusters of gonadotrophs were found surrounding the capillaries.
      No significant differences were detected in the number of gonadotrophs between
      sexually active and anestrous mares in either the PD or PT. In the PD,
      gonadotrophs represented 22.7 +/- 5. 8% and 19.1 +/- 2.1% of the total cell
      density in sexually active and anestrous animals, respectively (P: > 0.05).
      However, in the PT, gonadotrophs accounted for a higher proportion of the total
      cell population in sexually active (6 +/- 0.1%) than in anestrous (1.2 +/- 0.05%)
      mares (P: < 0.02). Double immunofluorescence revealed that the majority of
      gonadotrophs were bihormonal (i.e., positive for LH and FSH); however, in the
      sexually active mare, a larger proportion of gonadotrophs (22.5 +/- 3.6%) were
      monohormonal for either LH or FSH, when compared to anestrous animals (9.7 +/-
      1.2%; P: < 0.02). Based on these findings we conclude that: 1) although the
      relative distribution of gonadotrophs is similar to those reported for other
      species, a significantly larger proportion of gonadotroph cells is present in the
      equine pituitary gland; 2) gonadotroph density does not appear to differ between
      sexually active and anestrous mares in the PD; 3) a larger proportion of
      gonadotrophs is apparent in the PT of sexually active animals; and 4) although a
      large incidence of bihormonal gonadotrophs is present in the horse, specific LH
      or FSH cells differentiate predominantly during the sexually active phase.

PMID- 10952928
TI  - Lonidamine and analogue AF2785 block the cyclic adenosine 3', 5'-monophosphate
      activated chloride current and chloride secretion in the rat epididymis.
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. Mutation of the gene has led to widespread effects on male
      reproduction. Like other ion channels, CFTR is amenable to pharmacological
      intervention. Blocking CFTR in the epididymis could in principle lead to
      disruption of the epididymal fluid environment. We report for the first time two
      indazole compounds: lonidamine and 1-(2, 4-dichlorobenzyl)-indazole-3-acrylic
      acid (AF2785) are potent blockers of CFTR in the epididymis. When added to the
      external solution under whole-cell patch clamp conditions, AF2785 and lonidamine
      inhibited the cAMP-activated chloride current in rat epididymal cells with
      apparent IC(50) values of 170.6 and 631.5 microM, respectively; by comparison the
      IC(50) value for diphenylamine-2-carboxylate, a well-known chloride channel
      blocker was 1294 microM. In cultured rat epididymal epithelia mounted in a Ussing
      chamber, AF2785 and lonidamine inhibited the cAMP-stimulated short-circuit
      current (a measure of chloride secretion) when added to the apical bathing
      solution with potency greater than any known chloride channel studied. It is
      proposed that in view of the important role CFTR plays in male reproduction,
      further study with these and other new indazole compounds for their CFTR blocking
      actions can provide a new avenue of research into the development of novel male
      contraceptives.

PMID- 10952929
TI  - Oocyte-secreted factor(s) determine functional differences between bovine mural
      granulosa cells and cumulus cells.
AB  - Cumulus cells and mural granulosa cells (MGC) are phenotypically different and
      there is now evidence suggesting that the oocyte plays an active role in
      determining the fate of follicular somatic cells. This study investigates the
      role of oocyte-secreted factor(s) in the regulation of the growth and
      differentiation of cumulus and MGC. Bovine cumulus-oocyte complexes (COC) and MGC
      were cultured with various hormones for 18 h followed by a further 6-h pulse of
      [(3)H]thymidine as an indicator of follicular cell DNA synthesis. The COC
      incorporated 11 to 14 times more [(3)H]thymidine than MGC in either the absence
      or presence of 50 ng/ml insulin-like growth factor (IGF)-I. Purified porcine FSH
      (450 ng/ml) added together with IGF-I marginally increased (3)H incorporation in
      MGC relative to IGF-I alone but dramatically decreased incorporation in COC
      sixfold. Conversely, mean progesterone production in the presence of IGF-I + FSH
      was 13-fold higher from MGC than from COC, confirming a distinctive phenotype of
      cumulus cells. However, this phenotype was found to be dependent on the presence
      of the oocyte, as microsurgical removal of the oocyte (oocytectomy) resulted in
      an 11-fold decrease in [(3)H]thymidine incorporation in cumulus cells treated
      with IGF-I, elimination of the inhibitory effect of FSH on IGF-I-stimulated DNA
      synthesis, and led to a 2-fold increase in progesterone production in medium with
      IGF-I and FSH. All of these markers were completely restored to COC levels when
      oocytectomized complexes were cocultured with denuded oocytes (DO) at a
      concentration of 0.5 oocytes/microl, demonstrating that oocytes secrete a soluble
      factor(s) that promotes growth and attenuates cumulus cell progesterone
      secretion. In the presence of IGF-I, [(3)H]thymidine incorporation in MGC
      increased ninefold above control levels with the addition of DO. The addition of
      FSH to IGF-I-increased (3)H counts in MGC, however, led to a decrease in counts
      in MGC + DO as is also observed in COC. Furthermore, progesterone production was
      halved when DO were added to MGC cultures, most notably in the presence of IGF-I
      and/or FSH. These results provide further evidence that MGC and cumulus cells
      have distinctive phenotypes and that the oocyte is responsible for some of the
      characteristic features of cumulus cells. Bovine oocytes secrete a soluble
      factor(s) that simultaneously promotes growth and attenuates steroidogenesis in
      follicular somatic cells.

PMID- 10952930
TI  - Oxytocin signaling in human myometrium is impaired by prolonged exposure to
      interleukin-1.
AB  - Intra-amniotic infection leads to preterm labor and is associated with the local
      release of inflammatory cytokines by fetal membranes, resulting in the production
      of uterotonic prostaglandins. Oxytocin, however, also plays a key role in the
      initiation of labor. Short-term exposure of myometrium to interleukin (IL)-1
      enhances oxytocin signaling and contractility. With intrauterine infection,
      however, myometrium is exposed to inflammatory cytokines for prolonged periods.
      The present study was conducted to demonstrate that myometrial oxytocin signaling
      is significantly impaired following prolonged exposure to IL-1. Myometrial cells
      were treated with IL-1 for 24 h. Oxytocin-stimulated inositol trisphosphate
      (IP(3)) production was measured in tritiated myoinositol-loaded myometrial cells.
      Arachidonic acid (AA) release was measured in tritiated AA-loaded myometrial
      cells. Increases in intracellular calcium were measure with fluo-3. Prostaglandin
      (PG) F(2alpha) and 6-keto-PGF(1alpha) were measured by ELISA assay. Prolonged
      exposure of myometrial cells to IL-1 resulted in a significant reduction in
      oxytocin-mediated signaling as measured by IP(3) production and AA release, as
      well as a decrease in intracellular calcium. Prolonged exposure of myometrial
      cells to IL-1, however, resulted in enhanced PG release. Oxytocin may not
      contribute significantly to the labor-inducing action of IL-1 in the setting of
      preterm labor with prolonged infection.

PMID- 10952931
TI  - Noninvasive measurement of potassium efflux as an early indicator of cell death
      in mouse embryos.
AB  - Programmed cell death (apoptosis) occurs in nearly all cell types examined,
      including mammalian oocytes and embryos, where it may underlie some forms of
      infertility in humans. Although the molecular machinery participating in
      apoptosis have been intensely investigated, the accompanying physiological
      changes have not received similar attention. In this study, a novel
      electrophysiology technique has been employed to monitor real-time perturbations
      in the physiology of mouse embryos undergoing apoptosis evoked by hydrogen
      peroxide, diamide, and staurosporine. Despite differences in their mode of
      action, these agents evoked a similar early change in cellular physiology;
      namely, a pronounced, transient, potassium efflux through tetraethylammonium
      sensitive potassium channels accompanied by cell shrinkage. Mouse zygotes exposed
      to 200 microM H(2)O(2) exhibited potassium efflux that elevated the potassium
      concentration of the media surrounding embryos by 1.4 +/- 0.1 microM.
      Pretreatment with tetraethylammonium inhibited this increase (0.2 +/- 0.1
      microM). Our results indicate that potassium efflux through potassium channels
      and concurrent cell shrinkage are early indicators of cell death in embryos and
      that noninvasive measurements of potassium pathophysiology may identify embryos
      undergoing cell death prior to the manifestation of other morphological or
      molecular hallmarks of cell death.

PMID- 10952932
TI  - Vascular endothelial growth factor production in growing pig antral follicles.
AB  - Angiogenesis is the process that drives blood vessel development in growing
      tissues in response to the local production of angiogenic factors. With the
      present research the authors have studied vascular endothelial growth factor
      (VEGF) production in ovarian follicles as a potential mechanism of ovarian
      activity regulation. Prepubertal gilts were treated with 1250 IU equine chorionic
      gonadotropin (eCG) followed 60 h later by 750 IU of human chorionic gonadotropin
      (hCG) in order to induce follicle growth and ovulation. Ovaries were collected at
      different times of the treatment and single follicles were isolated and
      classified according to their diameter as small (<4 mm), medium (4-5 mm), or
      large (>5 mm). VEGF levels were measured in follicular fluid by enzyme
      immunoassay, and VEGF mRNA content was evaluated in isolated theca and granulosa
      compartments. Equine chorionic gonadotropin stimulated a prompt follicular growth
      and induced a parallel evident rise in VEGF levels in follicular fluid of medium
      and large follicles. Analysis of VEGF mRNA levels confirmed the stimulatory
      effect of eCG, showing that it is confined to granulosa cells, whereas theca
      cells maintained their VEGF steady state mRNA. Administration of hCG 60 h after
      eCG caused a dramatic drop in follicular fluid VEGF that reached undetectable
      levels in 36 h. A parallel reduction in VEGF mRNA expression was recorded in
      granulosa cells. The stimulating effect of eCG was also confirmed by in vitro
      experiments, provided that follicles in toto were used, whereas isolated follicle
      cells did not respond to this hormonal stimulation. Consistent with the
      observation in vivo, granulosa cells in culture reacted to hCG with a clear block
      of VEGF production. These results demonstrate that while follicles of untreated
      animals produce stable and low levels of the angiogenic factor, VEGF markedly
      rose in medium and large follicles after eCG administration. The increasing
      levels, essentially attributable to granulosa cells, are likely to be involved in
      blood vessel development in the wall of growing follicles, and may play a local
      key role in gonadotropin-induced follicle development. When ovulation approaches,
      under the effect of hCG, the production of VEGF is switched off, probably
      creating the safest conditions for the rupture of the follicle wall while theca
      cells maintained unaltered angiogenic activity, which is probably required for
      corpus luteum development.

PMID- 10952933
TI  - Insulin-like growth factor I increases follicle-stimulating hormone (FSH) content
      and gonadotropin-releasing hormone-stimulated FSH release from coho salmon
      pituitary cells in vitro.
AB  - The effects of insulin-like growth factor I (IGF-I) and insulin on the function
      of coho salmon gonadotropes in vitro were investigated. Dispersed pituitary cells
      from immature coho salmon (Oncorhynchus kisutch) were incubated with IGF-I for 1,
      3, 7, or 10 days, then incubated with salmon GnRH for an additional 24 h. Medium
      FSH content before and after GnRH treatment and intracellular FSH content after
      GnRH treatment were measured. Incubation of pituitary cells with IGF-I for 7 or
      10 days increased GnRH-stimulated FSH release and remaining cell content, but did
      not affect basal release. To examine the specificity of the effects of IGF-I, we
      compared FSH release and cell content of FSH and LH after 10-day incubation with
      a range of concentrations of IGF-I or insulin. Incubation with physiological
      concentrations of IGF-I resulted in significantly higher GnRH-stimulated FSH
      release and remaining cell content of FSH and LH. Conversely, supraphysiological
      concentrations of insulin were required to produce more moderate effects on
      gonadotropin levels. These results suggest that elevation of gonadotropin levels
      by IGF-I may be one mechanism by which somatic growth and nutrition promote
      pubertal development in salmon.

PMID- 10952935
TI  - Activation of nuclear factor kappaB and induction of apoptosis by tumor necrosis
      factor-alpha in the mouse uterine epithelial WEG-1 cell line.
AB  - In order to better understand how tumor necrosis factor (TNF)-alpha may
      contribute to the local regulation of uterine cell death, cultures of mouse
      uterine epithelial WEG-1 cells were exposed to TNF-alpha and observed at
      different time intervals. Earliest decrease in cell viability was observed after
      31 h of exposure to 50 ng/ml mouse TNF-alpha and was associated with the
      expression of several markers of apoptosis. Treatment with human TNF-alpha or
      addition of a neutralizing antibody against TNF-alpha receptor protein 80 to
      mouse TNF-alpha resulted in attenuated induction of apoptosis, suggesting that
      coengagement of the two TNF-alpha receptor types is required for maximal impact.
      Ceramide analogs failed to replicate the effect of TNF-alpha and the stress
      activated protein kinase signaling pathway was not activated by the cytokine.
      Treatment with mouse TNF-alpha resulted in an increase in nuclear factor
      (NF)kappaB activity that receded after 24 h. The impact of human TNF-alpha on
      NFkappaB activation was more moderate. Addition of either one of three different
      inhibitors of NFkappaB (SN50, PDTC, and A771726) to mouse TNF-alpha sensitized
      WEG-1 cells to the toxicity of the cytokine. Our data suggest that WEG-1 cells
      initiate their response to TNF-alpha with an increase in NFkappaB activation that
      may have transiently biased these cells toward cell death resistance.

PMID- 10952934
TI  - Cellular observations and hormonal correlates of feedback control of luteinizing
      hormone secretion by testosterone in long-term castrated male rhesus monkeys.
AB  - Testosterone at physiological levels cannot exert negative feedback action on LH
      secretion in long-term castrated male monkeys. The cellular basis of this
      refractoriness is unknown. To study it, we compared two groups of male rhesus
      macaques: one group (group 1, n = 4) was castrated and immediately treated with
      testosterone for 30 days; the second group (group 2, n = 4) was castrated and
      treated with testosterone for 9 days beginning 21 days after castration. Feedback
      control of LH by testosterone in group 1 was normal, whereas insensitivity to its
      action was found in group 2. Using the endpoints of concentrations of aromatase
      activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the
      medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we
      found that aromatase activity in both of these tissues was significantly lower,
      P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen
      receptor mRNA did not differ, however. Our data suggest that the cellular basis
      of testosterone insensitivity after long-term castration may reside in the
      reduced capacity of specific brain areas to aromatize testosterone. Because
      P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen
      dependent neural deficit, not involving the regulation of the P450(AROM) mRNA,
      occurs in long-term castrated monkeys.

PMID- 10952936
TI  - Effects of protease inhibitors and antioxidants on In vitro survival of porcine
      primordial germ cells.
AB  - One of the problems associated with in vitro culture of primordial germ cells
      (PGCs) is the large loss of cells during the initial period of culture. This
      study characterized the initial loss and determined the effectiveness of two
      classes of apoptosis inhibitors, protease inhibitors, and antioxidants on the
      ability of porcine PGCs to survive in culture. Results from electron microscopic
      analysis and in situ DNA fragmentation assay indicated that porcine PGCs rapidly
      undergo apoptosis when placed in culture. Additionally, alpha(2)-macroglobulin, a
      protease inhibitor and cytokine carrier, and N:-acetylcysteine, an antioxidant,
      increased the survival of PGCs in vitro. While other protease inhibitors tested
      did not affect survival of PGCs, all antioxidants tested improved survival of
      PGCs (P: < 0.05). Further results indicated that the beneficial effect of the
      antioxidants was critical only during the initial period of culture. Finally, it
      was determined that in short-term culture, in the absence of feeder layers,
      antioxidants could partially replace the effect(s) of growth factors and reduce
      apoptosis. Collectively, these results indicate that the addition of alpha(2)
      macroglobulin and antioxidants can increase the number of PGCs in vitro by
      suppressing apoptosis.

PMID- 10952937
TI  - Effects of thyroid and luteinizing hormones on the onset of precursor cell
      differentiation into leydig progenitor cells in the prepubertal rat testis.
AB  - Leydig cells in the adult rat testis differentiate during the neonatal
      prepubertal period. However, the stimulus for the initiation of their
      differentiation is still not clear. In the present study our objectives were to
      test the effects of thyroid hormone and LH on the initiation of precursor cell
      differentiation into Leydig cells in the prepubertal rat testis. Four groups of
      Sprague-Dawley rats were used. All treatments began at postnatal Day 1. Rats in
      groups I, II, and III received daily s.c. injections of saline (200 microl,
      controls), triiodothyronine (T(3), 50 microg/kg body weight, hyperthyroid), and
      LH (ovine LH 10 microg/rat/day), respectively. Rats in group IV were made
      hypothyroid from postnatal Day 1 by adding 0.1% propylthiouracil (PTU) to their
      mother's drinking water. Testes of rats were collected at 7, 8, 9, 10, 11, 12,
      16, and 21 days of age, fixed in Bouin's solution, and embedded in paraffin for
      immunocytochemical studies. Immunoexpression of 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) and LH receptors (LHR) in testicular interstitial cells
      (other than the fetal Leydig cells) was observed using the avidin-biotin method.
      In control rats, out of all spindle-shaped cell types in the testis interstitium,
      only the peritubular mesenchymal cells showed positive immunolabeling for 3beta
      HSD, beginning from the postnatal Day 11. However, positive immunolabeling for
      LHR was first detected in these cells at Day 12, i.e., after acquiring the
      steroidogenic enzyme activity. In T(3)-treated rats 3beta-HSD positive spindle
      shaped cells were first observed at Day 9 (i.e., 2 days earlier than controls),
      and LHR-positive cells were first observed on Day 11 (2 days later than obtaining
      3beta-HSD immunoactivity); they were exclusively the peritubular mesenchymal
      cells. The 3beta-HSD- and LHR-positive spindle-shaped cells were absent in the
      testis interstitium of LH-injected rats from Days 7 through 12 but were present
      at postnatal Day 16. In addition, more fetal Leydig cell clusters and fetal
      Leydig cells in mitosis were present in LH-treated rats compared to rats in all
      other treatment groups. Following their first detection, the number of positive
      cells for each protein continued to increase at each subsequent age in controls,
      T(3)-, and LH-injected groups. In PTU rats, 3beta-HSD and LHR-positive spindle
      shaped cells were absent throughout the experimental period. From these
      observations, it is possible to suggest the following regarding the developing
      rat testis interstitium. 1) The precursor cells for the adult generation of
      Leydig cells in the postnatal rat testis are the peritubular mesenchymal cells.
      2) Luteinizing hormone does not initiate the onset of mesenchymal cell
      differentiation into Leydig cells, instead it delays this process. However, daily
      LH treatment causes mitosis in fetal Leydig cells and increase in fetal Leydig
      cell clusters. 3) Thyroid hormone is critical to initiate the onset of
      mesenchymal cell differentiation into adult Leydig cells.

PMID- 10952938
TI  - Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered
      reproductive cyclicity and uterine morphology in reproductive-age female mice.
AB  - Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein
      expressed in the uterus of essentially all species, yet the function of this
      protein is uncertain. To assess the role of TIMP-1 in the uterine events that
      occur during the murine estrous cycle, mature female TIMP-1 wild-type and null
      mice were monitored for reproductive cyclicity. Mice were sacrificed in each
      stage of the estrous cycle, and peripheral blood was collected and assayed for
      serum estradiol and progesterone content by RIA. Uterine morphology and TIMP-1,
      TIMP-2, TIMP-3, and TIMP-4 mRNA expression were also examined between genotypes
      in each stage of the estrous cycle. Disruption of the TIMP-1 gene product was
      associated with an altered reproductive cycle characterized by a significant
      decrease in the length of the estrus period in the null mice. Also during the
      period of estrus, null mice expressed significantly lower levels of uterine TIMP
      3 mRNA expression, altered uterine morphology, significantly higher serum
      estradiol levels, and significantly lower serum progesterone levels compared to
      their wild-type counterparts. It is concluded from this study that TIMP-1 has a
      multifaceted role in regulating the murine reproductive cycle, and this control
      appears to be at the level of both the uterus and the ovary.

PMID- 10952939
TI  - Identification and immunolocalization of decorin, versican, perlecan, nidogen,
      and chondroitin sulfate proteoglycans in bovine small-antral ovarian follicles.
AB  - Proteoglycans (PGs) consist of a core protein and attached glycosaminoglycans
      (GAGs) and have diverse roles in cell and tissue biology. In follicles PGs have
      been detected only in follicular fluid and in cultured granulosa cells, and the
      composition of their GAGs has been determined. To identify PGs in whole ovarian
      follicles, not just in follicular fluid and granulosa cells, small (1-3-mm)
      bovine follicles were harvested. A proportion of these was incubated with
      (35)SO(4) for 24 h to incorporate radiolabel into the GAGs. The freshly harvested
      and cultured follicles were sequentially extracted with 6 M urea buffer, the same
      buffer with 0.1% Triton X-100 and then with 0.1 M NaOH. Proteoglycans were
      subjected to ion-exchange and size-exclusion chromatography. The GAGs were
      analyzed by chemical and enzymic digestion, and on the basis of their
      composition, we chose a list of known PGs to measure by ELISA analyses. Versican,
      perlecan, decorin, but not aggrecan or biglycan, were identified. These,
      excluding decorin for technical reasons, as well as a basal lamina glycoprotein,
      nidogen/entactin, were immunolocalized. Versican was localized to the thecal
      layers, including externa and the interna particularly in an area adjacent to the
      follicular basal lamina. Perlecan and nidogen were localized to the follicular
      basal lamina of antral follicles, both healthy and atretic, but not to that of
      preantral follicles. Both were localized to subendothelial basal laminas, but the
      former was not readily detected in arteriole smooth muscle layers. This study has
      confirmed the presence of versican and perlecan, but not the latter as a
      component of follicular fluid, and identified decorin and nidogen in ovarian
      antral follicles.

PMID- 10952940
TI  - Putative creatine kinase M-isoform in human sperm is identifiedas the 70
      kilodalton heat shock protein HspA2.
AB  - We previously described a putative creatine kinase M isoform in human sperm that
      is developmentally regulated and expressed during late spermiogenesis,
      simultaneous with cytoplasmic extrusion. We have now identified this protein as
      the testis-expressed 70-kDa heat shock protein chaperone known as HspA2 (the
      human homologue of mouse Hsp70-2). We have isolated and characterized HspA2
      (formerly CK-M) by amino acid sequencing and have localized it by
      immunocytochemistry to spermatocytes at low levels, to spermatids, and in the
      tail of mature sperm. The specificity of the CK-M/HspA2 antiserum to HspA2 was
      demonstrated on immunoblots of one- and two-dimensional SDS-PAGE. In agreement
      with our earlier biochemical data, immunocytochemistry of testicular tissue
      indicated that HspA2 is selectively expressed in mature spermatids and in sperm
      about to be released in the seminiferous tubuli. The identity of HspA2 has been
      further confirmed by cross-absorption of the mouse HSP70-2 antibody by the
      HspA2/CK-M fraction, and by identical immunostaining patterns of human testicular
      tissue using either the anti-CK-M/HspA2 or an anti-mouse Hsp70-2 antisera. During
      spermiogenesis, both cytoplasmic extrusion and plasma membrane remodeling, which
      facilitate the formation of the zona pellucida binding site, involve major
      intrasperm protein transport, which may be chaperoned by HspA2. Accordingly, in
      immature human sperm, which fail to express HspA2, there is cytoplasmic retention
      and lack of zona pellucida binding. The present findings provide the biological
      rationale for the role of the human HspA2 as an objective biochemical marker of
      sperm function and male fertility, which we have established in earlier clinical
      studies.

PMID- 10952941
TI  - Expression of cyclooxygenase 2 by prostaglandin E(2) in human endometrial
      adenocarcinoma cell line HEC-1B.
AB  - The regulation of expression of cyclooxygenase 2 (COX-2) was investigated by
      treatment with PGE(2) in human endometrial adenocarcinoma cell line HEC-1B. One
      microM PGE(2) could stimulate the expression of COX-2 approximately twofold in
      this cell line. The same concentration of PGE(2) also stimulated activation of
      mitogen-activated protein kinase (MAP kinase) and protein kinase B (PKB). PGE(2)
      induced MAP kinase activation was sensitive to a MAP kinase kinase (MEK)
      inhibitor, PD098059, and a protein kinase A inhibitor, H-89. PD098059 and H-89
      also partially inhibited the expression of COX-2 stimulated by PGE(2). PGE(2)
      could stimulate the activation of PKB, which was sensitive to
      phosphatidylinositol-3-OH kinase (PI3K) inhibitor, wortmannin. Whereas wortmannin
      alone partially inhibited the expression of COX-2, a combination of wortmannin
      and PD098059 totally inhibited PGE(2)-mediated COX-2 expression. These results
      suggest that MAP kinase and PI3K pathways are stimulated with PGE(2), and that
      both of these pathways are involved in the expression of COX-2. In addition, they
      also suggest that protein kinase A remains upstream of PGE(2)-induced activation
      of MAP kinase in HEC-1B cells.

PMID- 10952942
TI  - Growth and the initiation of steroidogenesis in porcine follicles are associated
      with unique patterns of gene expression for individual componentsof the ovarian
      insulin-like growth factor system.
AB  - Ovarian follicular growth and steroidogenesis are controlled by the interaction
      of insulin-like growth factors (IGFs) and gonadotropins. The objective was to
      determine the temporal and spatial relationships for gonadotropin receptor,
      steroidogenic enzyme, and IGF system gene expression during the development of
      preovulatory porcine follicles. Sows (n = 18) were weaned and follicles were
      monitored by transrectal ultrasonography. Ovaries were collected from sows when
      the mean diameter of the preovulatory follicular cohort was approximately 2, 4,
      6, or 8 mm. mRNA were measured by in situ hybridization for individual follicles
      within the preovulatory cohort (3 to 5 follicles per sow). Patterns of gene
      expression detected by in situ hybridization were confirmed by RNase protection
      analyses of pooled RNA samples. The amount of LH receptor mRNA and steroidogenic
      enzyme mRNA (17alpha-hydroxylase and aromatase) increased as the mean diameter of
      the follicular cohort increased from 2 to 6 mm, but then decreased abruptly for 8
      mm follicles. Estradiol concentrations in follicular fluid closely followed the
      expression patterns of steroidogenic enzymes and LH receptor mRNA. FSH receptor
      mRNA was present in cohorts of 2-mm follicles but declined in 4-mm follicles and
      was undetectable in 6- and 8-mm follicles. The expression of IGF-I and type I IGF
      receptor mRNA were similar for follicles of 2, 4, 6, and 8 mm. In contrast, IGF
      II mRNA progressively increased in follicles collected from 2-, 4-, and 6-mm
      cohorts, and then decreased slightly at 8 mm. Type II IGF receptor mRNA was
      greatest in 8-mm follicles. IGF binding protein-2 (BP-2) mRNA decreased as
      follicles achieved progressively larger sizes during the preovulatory period (2
      to 8 mm), whereas the IGFBP-4 mRNA remained relatively low for follicles in 2- to
      6-mm cohorts but then increased markedly in 8-mm follicles. In summary, temporal
      and spatial patterns of gene expression for gonadotropin receptor, steroidogenic
      enzyme, and IGF system genes were characterized in preovulatory porcine follicles
      by using in situ hybridization and RNase protection analyses. The unique patterns
      of gene expression suggest interdependence among specific genes that may be
      essential for preovulatory follicular development.

PMID- 10952943
TI  - Role of the vomeronasal organ in neonatal offspring recognition in sheep.
AB  - Twenty-five pregnant Dorsett ewes were randomly divided into three groups to test
      if ewes use their vomeronasal organs for offspring recognition during nursing.
      One group of eight ewes (procaine) were made anosmic by irrigation of the nasal
      olfactory apparatus with a zinc sulphate procaine solution. The second group of
      nine ewes (cauterized) had their vomeronasal organs rendered nonfunctional by
      cauterization of the nasoincisive duct. The third group of eight ewes were the
      controls. Parturition was synchronized in all ewes with betamethasone on Day 145
      of gestation. Maternal responsiveness was tested two separate times with 1- to 2
      day-old alien lambs. Each alien lamb trial was conducted 24 h apart. Cauterized
      ewes allowed alien lambs to suckle and they were unable to distinguish alien
      lambs from their own lambs, whereas the ewes in both groups with functional
      vomeronasal organs (procaine and control) violently rejected any alien lamb's
      attempt to suckle. Thus, female sheep use their vomeronasal organs for neonatal
      offspring recognition.

PMID- 10952944
TI  - Fibroblast growth factor-10: a stromal mediator of epithelial function in the
      ovine uterus.
AB  - Fibroblast growth factor-10 (FGF-10) is a stromal-derived paracrine growth factor
      considered to be important during embryogenesis; however, its expression by cells
      in the female reproductive tract has not been investigated. Therefore, an ovine
      FGF-10 cDNA was cloned from an ovine endometrial cDNA library to investigate
      expression and potential paracrine characteristics of FGF-10 in the ovine uterus.
      The ovine FGF-10 cDNA encodes a protein of 213 amino acids and possesses an
      unusually long 5' untranslated region (UTR). In situ hybridization demonstrated
      that ovine FGF-10 mRNA was expressed by endometrial stromal cells and by
      mesenchymal cells of the chorioallantoic placenta. The mRNA for FGF-7, a
      homologue of FGF-10, was localized in the tunica muscularis of blood vessels in
      endometrium and myometrium. In contrast, FGF receptor 2IIIb, the high-affinity
      receptor for both FGF-10 and FGF-7, was expressed exclusively in luminal
      epithelium, glandular epithelium, and placental trophectoderm. The in vivo
      spatial expression pattern suggests that FGF-10 is a novel endometrial stromal
      cell-derived mediator of uterine epithelial and conceptus trophectodermal
      functions. The nonoverlapping spatial patterns of expression for FGF-10 and FGF-7
      in ovine uterus and conceptus suggest independent roles in uterine function and
      conceptus development.

PMID- 10952945
TI  - Cardiovascular benefit of cholesterol-lowering therapy: does improved endothelial
      vasodilator function matter?

PMID- 10952946
TI  - Revisiting the question: will relaxing safe current limits for electromedical
      equipment increase hazards to patients?

PMID- 10952947
TI  - Monitoring embolism in real time.

PMID- 10952948
TI  - Angiotensin-converting enzyme insertion/deletion polymorphism modulates the human
      in vivo metabolism of bradykinin.
AB  - BACKGROUND: Bradykinin is a cardioprotective peptide metabolized by the
      angiotensin-converting enzyme (ACE). An insertion/deletion (I/D) polymorphism in
      the ACE gene determines plasma ACE levels. The D allele is associated with
      cardiovascular disease, which may relate to enhanced angiotensin II production or
      to increased bradykinin degradation to the inactive metabolite bradykinin 1-5
      (BK1-5). Therefore, we determined the effect of the ACE I/D polymorphism on human
      bradykinin metabolism in vivo. METHODS AND RESULTS: Bradykinin (400 ng/min) was
      infused into the brachial artery of volunteers with ACE I/I, I/D, or D/D
      genotypes (n=9 each). The bradykinin and BK1-5 levels in forearm venous return
      were quantified by liquid chromatography-mass spectroscopy. Plasma ACE activity
      was highest in those with the D/D genotype (36.8+/-6.2 U/mL), intermediate in
      those with the I/D genotype (25.3+/-3.3 U/mL), and lowest in those with the I/I
      genotype (20.3+/-2.3 U/mL; P=0.017 for effect of number of D alleles). Bradykinin
      concentrations were 726+/-242, 469+/-50, and 545+/-104 fmol/mL in I/I, I/D, and
      D/D subjects, respectively (P>0. 10). Significant correlations existed between
      the number of D alleles and BK1-5 concentrations (1113+/-290, 1520+/-318, and
      1887+/-388 fmol/mL in the I/I, I/D, and D/D groups, respectively; P=0.027) and
      the ratio of BK1-5 to bradykinin (1.87+/-0.35, 3.09+/-0. 40, and 4.31+/-0.97 in
      the I/I, I/D, and D/D volunteers, respectively; P=0.010). The venous blood BK1
      5:bradykinin ratio correlated with plasma ACE activity (r(2)=0.16, P=0.039), and
      total kinin concentration correlated with net tissue plasminogen activator
      release across the forearm (r(2)=0.20, P=0.027). CONCLUSIONS: The ACE D allele
      has a significant effect on the in vivo degradation of bradykinin in humans. The
      ratio of BK1-5:bradykinin may serve as a marker for tissue ACE activity.

PMID- 10952949
TI  - Infections, immunity, and atherosclerosis: associations of antibodies to
      Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune
      reactions to heat-shock protein 60 and carotid or femoral atherosclerosis.
AB  - BACKGROUND: Atherogenesis involves inflammatory processes in which infections are
      incriminated as possible contributors. METHODS AND RESULTS: We evaluated
      cardiovascular risk factors as well as seropositivity to Chlamydia pneumoniae,
      Helicobacter pylori, and cytomegalovirus in a population-based study. A
      significant association between prevalence and severity of atherosclerosis in
      carotid and femoral arteries and IgA antibodies to C pneumoniae was demonstrated
      that was not substantially altered after adjustment for established risk factors.
      For anti-H pylori IgG antibodies, significant correlations to vascular disease
      were restricted to low social status and lesions in carotid arteries. In
      addition, the study design allowed us to monitor lesion progression over time. In
      this prospective analysis, C pneumoniae seropositivity emerged as a significant
      risk predictor. Antibody titers against cytomegalovirus were not a marker for
      prevalence or incidence of atherosclerosis in this population. Further infection
      parameters added to the predictive value of chlamydial serology in risk
      assessment: Mean odds ratios for the prevalence of carotid atherosclerosis were
      4.2 and 6.3 for seropositive subjects with elevated C-reactive protein levels and
      clinical evidence for chronic respiratory infection, respectively. For subjects
      with all 3 infection parameters, the odds ratio of carotid atherosclerosis
      reached 10.3 (P<0.0001). Concomitantly, serum antibodies to mycobacterial heat
      shock protein 65 (mHSP65) correlated with seropositivity to C pneumoniae and H
      pylori but not to cytomegalovirus. CONCLUSIONS: This prospective population-based
      study provides strong evidence for a potential atherogenic role of persistent
      bacterial infection, especially C pneumoniae, as indicated by serological and
      clinical data and demonstrates a correlation between immune reactions to mHSP65
      and bacterial infections in atherogenesis.

PMID- 10952951
TI  - Effect of cholesterol-lowering therapy on coronary endothelial vasomotor function
      in patients with coronary artery disease.
AB  - BACKGROUND: Improved endothelial function may contribute to the beneficial
      effects of cholesterol-lowering therapy. METHODS AND RESULTS: In this randomized,
      double-blind study, we compared the effect of 6 months of simvastatin (40 mg/d)
      treatment with that of placebo on coronary endothelial vasomotor function in 60
      patients with coronary artery disease. Simvastatin lowered LDL-cholesterol by
      40+/-12% from 130+/-28 mg/dL (P<0.001). Peak intracoronary acetylcholine infusion
      produced epicardial coronary constriction at baseline in both the simvastatin (
      17+/-13%) and placebo (-24+/-16%) groups. After treatment, acetylcholine produced
      less constriction in both groups (-12+/-19% and -15+/-14%, respectively, P=0.97).
      The increase in coronary blood flow during infusion of the peak dose of substance
      P was blunted at baseline in both the simvastatin (42+/-50%) and placebo (55+/
      71%) groups, reflecting impaired endothelium-dependent dilation of coronary
      microvessels. After treatment, the flow increase was 82+/-81% in the simvastatin
      group and 63+/-53% in the placebo group (P=0.16). CONCLUSIONS: Six months of
      cholesterol-lowering therapy has no significant effect on coronary endothelial
      vasomotor function in the study population of patients with coronary artery
      disease and mildly elevated cholesterol levels. These findings suggest that the
      effects of cholesterol lowering on endothelial function are more complex than
      previously thought.

PMID- 10952950
TI  - Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with
      atherosclerosis.
AB  - BACKGROUND: The formation of prostacyclin (PGI(2)), thromboxane (TX) A(2), and
      isoprostanes is markedly enhanced in atherosclerosis. We examined the relative
      contribution of cyclooxygenase (COX)-1 and -2 to the generation of these
      eicosanoids in patients with atherosclerosis. METHODS AND RESULTS: The study
      population consisted of 42 patients with atherosclerosis who were undergoing
      surgical revascularization. COX-2 mRNA was detected in areas of atherosclerosis
      but not in normal blood vessel walls, and there was evidence of COX-1 induction.
      The use of immunohistochemical studies localized the COX-2 to proliferating
      vascular smooth muscle cells and macrophages. Twenty-four patients who did not
      previously receive aspirin were randomized to receive either no treatment or
      nimesulide at 24 hours before surgery and then for 3 days. Eighteen patients who
      were receiving aspirin were continued on a protocol of either aspirin alone or a
      combination of aspirin and nimesulide. Urinary levels of 11-dehydro-TXB(2) and
      2,3-dinor-6-keto-PGF(1alpha), metabolites of TXA(2) and PGI(2), respectively,
      were elevated in patients with atherosclerosis compared with normal subjects
      (3211+/-533 versus 679+/-63 pg/mg creatinine, P<0.001; 594+/-156 versus 130+/-22
      pg/mg creatinine, P<0.05, respectively), as was the level of the isoprostane 8
      iso-PGF(2alpha). Nimesulide reduced 2, 3-dinor-6-keto-PGF(1alpha) excretion by
      46+/-5% (378.3+/-103 to 167+/-37 pg/mg creatinine, P<0.01) preoperatively and
      blunted the increase after surgery. Nimesulide had no significant effect on 11
      dehydro-TXB(2) before (2678+/-694 to 2110+/-282 pg/mg creatinine) or after
      surgery. The levels of both products were lower in patients who were taking
      aspirin, and no further reduction was seen with the addition of nimesulide. None
      of the treatments influenced urinary 8-iso-PGF(2alpha) excretion. CONCLUSIONS:
      Both COX-1 and -2 are expressed and contribute to the increase in PGI(2) in
      patients with atherosclerosis, whereas TXA(2) is generated by COX-1.

PMID- 10952952
TI  - Effect of dietary patterns on serum homocysteine: results of a randomized,
      controlled feeding study.
AB  - BACKGROUND: Elevated blood levels of homocysteine are associated with an
      increased risk of atherosclerotic cardiovascular disease. Although numerous
      studies have assessed the impact of vitamin supplements on homocysteine, the
      effect of dietary patterns on homocysteine has not been well studied. METHODS AND
      RESULTS: During a 3-week run-in, 118 participants were fed a control diet, low in
      fruits, vegetables, and dairy products, with a fat content typical of US
      consumption. During an 8-week intervention phase, participants were then fed 1 of
      3 randomly assigned diets: the control diet, a diet rich in fruits and vegetables
      but otherwise similar to control, or a combination diet rich in fruits,
      vegetables, and low-fat dairy products and reduced in saturated and total fat.
      Between the end of run-in and intervention periods, mean change in homocysteine
      was +0.46 micromol/L in the control diet, +0.21 micromol/L in the fruits and
      vegetables diet (P=0.47 compared with control), and -0.34 micromol/L in the
      combination diet (P=0.03 compared with control, P=0.12 compared with the fruits
      and vegetables diet). In multivariable regression models, change in homocysteine
      was significantly and inversely associated with change in serum folate (P=0.03)
      but not with change in serum vitamin B(12) (P=0.64) or pyridoxal 5' phosphate,
      the coenzyme form of vitamin B(6) (P=0.83). CONCLUSIONS: Modification of dietary
      patterns can have substantial effects on fasting levels of total serum
      homocysteine. These results provide additional insights into the mechanisms by
      which diet might influence the occurrence of atherosclerotic cardiovascular
      disease.

PMID- 10952953
TI  - Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large
      non-referral-based patient population.
AB  - BACKGROUND: Death resulting from hypertrophic cardiomyopathy (HCM), particularly
      when sudden, has been reported to be largely confined to young persons. These
      data emanated from tertiary HCM centers with highly selected referral patterns
      skewed toward high-risk patients. METHODS AND RESULTS: The present analysis was
      undertaken in an international population of 744 consecutively enrolled and
      largely unselected patients more representative of the overall HCM spectrum. HCM
      related death occurred in 86 patients (12%) over 8+/-7 years (mean+/-SD). Three
      distinctive modes of death were as follows: (1) sudden and unexpected (51%; age,
      45+/-20 years); (2) progressive heart failure (36%; age, 56+/-19 years); and (3)
      HCM-related stroke associated with atrial fibrillation (13%; age, 73+/-14 years).
      Sudden death was most common in young patients, whereas heart failure- and stroke
      related deaths occurred more frequently in midlife and beyond. However, neither
      sudden nor heart failure-related death showed a statistically significant,
      disproportionate age distribution (P=0.06 and 0.5, respectively). Stroke-related
      deaths did occur disproportionately in older patients (P=0.002). Of the 45
      patients who died suddenly, most (71%) had no or mild symptoms, and 7 (16%)
      participated in moderate to severe physical activities at the time of death.
      CONCLUSIONS: HCM-related cardiovascular death occurred suddenly, or as a result
      of heart failure or stroke, largely during different phases of life in a
      prospectively assembled, regionally based, and predominantly unselected patient
      cohort. Although most sudden deaths occurred in adolescents and young adults,
      such catastrophes were not confined to patients of these ages and extended to
      later phases of life. This revised clinical profile suggests that generally held
      epidemiological tenants for HCM have been influenced considerably by skewed
      reporting from highly selected populations. These data are likely to importantly
      affect risk stratification and treatment strategies importantly for the
      prevention of sudden death in HCM.

PMID- 10952954
TI  - Plasma brain natriuretic peptide as a prognostic indicator in patients with
      primary pulmonary hypertension.
AB  - BACKGROUND: Plasma brain natriuretic peptide (BNP) level increases in proportion
      to the degree of right ventricular dysfunction in pulmonary hypertension. We
      sought to assess the prognostic significance of plasma BNP in patients with
      primary pulmonary hypertension (PPH). METHODS AND RESULTS: Plasma BNP was
      measured in 60 patients with PPH at diagnostic catheterization, together with
      atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were
      repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of
      the patients received intravenous or oral prostacyclin. During a mean follow-up
      period of 24 months, 18 patients died of cardiopulmonary causes. According to
      multivariate analysis, baseline plasma BNP was an independent predictor of
      mortality. Patients with a supramedian level of baseline BNP (>/=150 pg/mL) had a
      significantly lower survival rate than those with an inframedian level, according
      to Kaplan-Meier survival curves (P<0.05). Plasma BNP in survivors decreased
      significantly during the follow-up (217+/-38 to 149+/-30 pg/mL, P<0. 05), whereas
      that in nonsurvivors increased (365+/-77 to 544+/-68 pg/mL, P<0.05). Thus,
      survival was strikingly worse for patients with a supramedian value of follow-up
      BNP (>/=180 pg/mL) than for those with an inframedian value (P<0.0001).
      CONCLUSIONS: A high level of plasma BNP, and in particular, a further increase in
      plasma BNP during follow-up, may have a strong, independent association with
      increased mortality rates in patients with PPH.

PMID- 10952955
TI  - Does folic acid decrease plasma homocysteine and improve endothelial function in
      patients with predialysis renal failure?
AB  - BACKGROUND: Considerable evidence suggests that hyperhomocysteinemia is an
      independent vascular risk factor that promotes atherosclerosis by inducing
      endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the
      effect on adverse vascular events is unknown. We hypothesized that in patients
      with chronic renal failure, a condition associated with both hyperhomocysteinemia
      and atherosclerosis, treatment with folic acid would improve endothelial
      function. METHODS AND RESULTS: In a prospective, double-blind protocol, 100
      patients (mean age 62 years, 67 men) with predialysis chronic renal failure were
      randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function
      was assessed by measuring (1) endothelium-dependent dilation of the brachial
      artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von
      Willebrand factor concentration. Baseline characteristics of the 2 groups were
      similar. At the end of the study, both serum and red cell folate concentrations
      were greater in the folic acid group than the placebo group [mean (95% CI) 39.0
      (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220
      (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in
      hyperhomocysteinemia in the folic acid group compared with the placebo group
      [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were
      no significant differences in endothelium-dependent dilation, combined serum
      nitrite/nitrate concentrations, or plasma von Willebrand factor concentration
      between the 2 groups. CONCLUSIONS: High-dose folic acid lowers but fails to
      normalize hyperhomocysteinemia in patients with predialysis chronic renal
      failure. This was not accompanied by an improvement of endothelial function and
      suggests that treatment with folic acid may not reduce the burden of vascular
      disease in uremia.

PMID- 10952956
TI  - Sudden death and cardiovascular collapse in children with restrictive
      cardiomyopathy.
AB  - BACKGROUND: Restrictive cardiomyopathy (RCM) is rare in children, and the
      prognosis is poor. In the present study, we evaluated all pediatric patients with
      RCM who were at our institution during a 31-year period to determine the clinical
      outcome and cause of death. Those who sustained sudden, unanticipated cardiac
      arrests were evaluated for risk factors that are predictive of sudden death.
      METHODS AND RESULTS: Eighteen consecutive patients were reviewed. Presentation,
      clinical course, laboratory data, and histopathological evidence of ischemia were
      compared between patients with and without sudden death events. The results
      demonstrated that patients who were at risk for sudden death were girls with
      chest pain, syncope, or both at presentation and without congestive heart
      failure. Although not statistically significant for sudden death, Holter monitor
      evidence of ischemia predicted death within months. Histopathological evidence of
      acute or chronic ischemia was found in the majority of patients, with acute
      ischemia more common among those who sustained sudden death events. CONCLUSIONS:
      All children with RCM are at risk for ischemia-related complications and death,
      and some are at risk of sudden death. In the present study, patients at risk of
      sudden death appeared well and had no evidence of ongoing heart failure but often
      had signs or symptoms of ischemia characterized by chest pain, syncope, or both.
      ECGs and Holter monitors may be useful screening tools. The use of beta-blockade,
      the placement of an implantable cardioverter-defibrillator, and preferential
      status 1A or B listing for cardiac transplantation are proposed for pediatric
      patients with RCM and evidence of ongoing ischemia.

PMID- 10952957
TI  - Cognitive development after the Fontan operation.
AB  - BACKGROUND: Patients with a single ventricle have multiple risk factors for
      central nervous system injury, both before and after the Fontan procedure.
      METHODS AND RESULTS: A geographically selected cohort was invited to undergo
      standardized testing, including age-appropriate measures of intelligence quotient
      (IQ) and achievement tests. Historical information was obtained by chart review
      and patient questionnaires. Of the 222 eligible patients, 133 (59.9%)
      participated. Median age at testing was 11.1 years (range, 3. 7 to 41.0 years),
      6.0 years (range, 1.6 to 19.6 years) after surgery. Mean full-scale IQ was 95.7+/
      17.4 (P<0.006 versus normal); 10 patients (7.8%) had full-scale IQ scores <70
      (P=0.001). After adjustment for socioeconomic status, lower IQ was associated
      with the use of circulatory arrest before the Fontan operation (P=0.002), the
      anatomic diagnoses of hypoplastic left heart syndrome (P<0.001) and "other
      complex" (P=0.05), and prior placement of a pulmonary artery band (P=0.04). Mean
      composite achievement score was 91.6+/-15. 4 (P<0.001 versus normal); 14 patients
      (10.8%) scored <70 (P<0.001). After adjustment for socioeconomic status,
      independent risk factors for low achievement scores included the diagnoses of
      hypoplastic left heart syndrome (P=0.004) and "other complex" (P=0.003) or prior
      use of circulatory arrest (P=0.03), as well as a reoperation with cardiopulmonary
      bypass within 30 days of the Fontan (P=0.01). CONCLUSIONS: Most individual
      patients palliated with the Fontan procedure in the 1970s and 1980s have
      cognitive outcome and academic function within the normal range, but the
      performance of the cohort is lower than that of the general population.

PMID- 10952958
TI  - Changes in surface expression of platelet membrane glycoproteins and progression
      of heart transplant vasculopathy.
AB  - BACKGROUND: Transplant vasculopathy is the main limiting factor of the long-term
      success of heart transplantation. We sought to establish the role of platelets in
      the development and progression of transplant vasculopathy. METHODS AND RESULTS:
      Platelet analysis and intracoronary ultrasound examination were performed in 78
      heart transplant recipients. Quantitative intracoronary ultrasound was used to
      define the severity of disease at baseline (48.8+/-4.5 months after
      transplantation) and at 1-year follow-up. Platelet activation was assessed with
      the use of immunological surface markers of activation (ligand-induced binding
      site 1 [LIBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1
      immunoreactivity was significantly increased in patients with diffuse disease
      when compared with focal transplant disease (median [quartile], 27[14, 64] versus
      18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an
      independent predictor for the presence and progression of diffuse transplant
      vasculopathy (P=0.04). Patients with enhanced LIBS-1 levels (>75% quartile) had a
      3.3-fold increased relative risk (95% CI 1.8 and 18.9, P=0.002) for the presence
      of diffuse transplant vasculopathy. When a cutoff value of 16.5 for the level of
      LIBS-1 was used, patients had a 4.8-fold increased relative risk (95% CI 1.9 and
      12.5, P<0.01) for the progression of transplant vasculopathy. CONCLUSIONS:
      Enhanced platelet activation is strongly associated with the development and
      progression of transplant vasculopathy. Understanding the underlying
      pathophysiological mechanisms might contribute to the development of treatment
      strategies to prevent transplant vasculopathy.

PMID- 10952959
TI  - VEGF gene delivery to myocardium: deleterious effects of unregulated expression.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is being investigated for
      therapeutic angiogenesis in ischemic myocardium. Primarily, transient delivery
      systems have been tested. The goal of this study was to investigate the effects
      of continuous expression of VEGF in myocardium by use of myoblast-mediated
      delivery. METHODS AND RESULTS: Primary murine myoblasts (5 x 10(5) cells in 10
      microL of PBS with 0.5% BSA) expressing both the murine VEGF gene and the beta
      galactosidase (beta-gal) gene from a retroviral promoter were implanted in the
      ventricular wall of immunodeficient mice (n=11) via a subdiaphragmatic approach.
      Control immunodeficient mice (n=12) were injected with the same number of
      myoblasts expressing only the beta-gal gene. Between days 14 and 16, surviving
      mice were euthanized and the hearts processed for histology. In the experimental
      group, 11 of 11 mice demonstrated failure to thrive by day 13; 5 deaths occurred
      between days 8 and 15. There were no complications in the control mice.
      Histochemistry documented successful implantation of myoblasts (positive beta-gal
      reaction product) in 6 of 6 surviving experimental mice and 12 of 12 controls.
      Histology disclosed intramural vascular tumors resembling hemangiomas in the VEGF
      myoblast-injected myocardium in 6 of 6 surviving mice. beta-Gal-expressing cells
      were present at the site of the vascular tumors. Immunohistochemistry localized
      abundant endothelial nitric oxide synthase and CD31 (platelet and endothelial
      cell adhesion molecule) within the lesion, consistent with the presence of
      endothelial cells. CONCLUSIONS: In this model, unregulated continuous expression
      of VEGF is associated with (1) a high rate of failure to thrive/death and (2)
      formation of endothelial cell-derived intramural vascular tumors in the
      implantation site. These results underscore the importance of regulating VEGF
      expression for therapeutic angiogenesis.

PMID- 10952960
TI  - Inducible nitric oxide synthase mediates delayed myocardial protection induced by
      activation of adenosine A(1) receptors: evidence from gene-knockout mice.
AB  - BACKGROUND: The mechanism of delayed preconditioning induced by activation of
      adenosine A(1) receptors (A(1)ARs) is not fully understood. We determined the
      role of inducible nitric oxide synthase (iNOS) in mediating adenosine-induced
      late cardioprotection using pharmacological inhibitors and iNOS gene-knockout
      mice. METHODS AND RESULTS: Adult male mice were treated with saline or an A(1)AR
      agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA). Twenty-four hours later, the
      hearts were perfused in Langendorff mode and subjected to 30 minutes of global
      ischemia followed by 30 minutes of reperfusion. 8-Cyclopentyl-1,3
      dipropylxanthine (DPCPX; 0.1 mg/kg IP) and S-methylisothiourea (SMT; 3 mg/kg IP)
      were used to block A(1)ARs and iNOS, respectively. Infarct size (IS) was measured
      by triphenyltetrazolium chloride staining, and iNOS expression was measured by
      Western blots. Myocardial IS was reduced from 24.0+/-3. 2% in the saline group to
      12.2+/-2.5% in CCPA-treated mice (P<0.05). The infarct-reducing effect of CCPA
      was abrogated by DPCPX (29.3+/-3. 4%) and SMT (32.3+/-2.6%) and was absent in
      mice with targeted ablation of iNOS (23.9+/-1.6%). CCPA produced improvement in
      postischemic end-diastolic pressure, developed pressure, and rate-pressure
      product, which was also blocked by DPCPX and SMT. Increased iNOS protein
      expression observed in CCPA-treated hearts was diminished by DPCPX. CONCLUSIONS:
      Selective activation of A(1)ARs produces delayed cardioprotection against
      ischemia/reperfusion injury in the mouse. Increased iNOS expression concomitant
      with the lack of protective effect of A(1)AR activation in iNOS gene-knockout
      mice suggests a direct cause-and-effect relationship of iNOS in adenosine-induced
      late cardioprotection.

PMID- 10952961
TI  - Spatial heterogeneity in fasting and insulin-stimulated (18)F-2-deoxyglucose
      uptake in pigs with hibernating myocardium.
AB  - BACKGROUND: Previous studies of hibernating myocardium in the fasting state have
      shown regionally increased (18)F-2-deoxyglucose (FDG) uptake with a marked
      transmural gradient. We hypothesized that this adaptation to chronic ischemia
      might be associated with altered maximal FDG uptake. METHODS AND RESULTS: Pigs
      were instrumented with a 1.5-mm proximal left anterior descending artery (LAD)
      stenosis. Studies were conducted 106+/-4 days later on anesthetized animals with
      complete LAD occlusion and anteroapical dysfunction. In fasting animals (n=9),
      FDG uptake in dysfunctional LAD regions was 2-fold higher than in normally
      perfused myocardium (7.9+/-1.2 versus 4. 0+/-0.5 micromol x min(-1) x 100 g(-1),
      P<0.05), with a pronounced transmural gradient (endocardial/epicardial ratio
      2.56+/-0.19 versus 1.25+/-0.03, P<0.05). Euglycemic, hyperinsulinemic clamp
      (insulin clamp, n=8) produced a 5- to 9-fold increase in FDG uptake, but there
      was no longer a regional difference in accumulation (LAD, 37. 8+/-4.2 versus
      normal, 36.4+/-5.1 micromol x min(-1) x 100 g(-1), P=NS) and the transmural
      distribution was uniform. FDG uptake in the fasting state varied inversely with
      coronary flow during vasodilation. In contrast, during insulin clamp there was no
      relation between FDG uptake and vasodilated flow, resulting in a reduced spatial
      heterogeneity in individual samples (relative dispersion=SD/mean; fasting, 52+/
      5% versus insulin, 24+/-2%, P<0.05). CONCLUSIONS: In the fasting state, FDG
      uptake in pigs with hibernating myocardium was heterogeneous and was increased in
      dysfunctional regions with a marked transmural gradient and high spatial
      heterogeneity. In contrast, FDG uptake was more homogeneously distributed during
      insulin clamp with (1) uptake in dysfunctional myocardium similar to remote
      normal regions, (2) uniform transmural distribution, and (3) reduced spatial
      heterogeneity.

PMID- 10952962
TI  - Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia.
AB  - BACKGROUND: The death of cardiac cells during ischemia and reperfusion is
      partially mediated by apoptosis, as seen, eg, in autopsy material of patients
      after acute myocardial infarction. METHODS AND RESULTS: To study the role of
      CD95/Fas/Apo1 for induction of postischemic cell death, we used an
      ischemia/reperfusion model of isolated rat and mouse hearts in Langendorff
      perfusion. In this model, caspase-dependent apoptosis occurred during
      postischemic reperfusion. Moreover, soluble CD95 ligand/Fas ligand was released
      by the postischemic hearts early after the onset of reperfusion. In addition,
      this ligand was synthesized de novo under these circumstances. Similar findings
      were observed for other "death-inducing" ligands, such as tumor necrosis factor
      (TNF)-alpha and TNF-related apoptosis-inducing ligand. In primary adult rat
      myocyte culture, hypoxia and reoxygenation caused a marked increase in
      sensitivity to the apoptotic effects of CD95 ligand. Isolated hearts from mice
      lacking functional CD95 (lpr) display marked reduction in cell death after
      ischemia and reperfusion compared with wild-type controls. CONCLUSIONS: These
      data suggest that CD95/Apo1/Fas is directly involved in cell death after
      myocardial ischemia. The CD95 system might thus represent a novel target for
      therapeutic prevention of postischemic cell death in the heart.

PMID- 10952963
TI  - Molecular pharmacology of the sodium channel mutation D1790G linked to the long
      QT syndrome.
AB  - BACKGROUND: Multiple mutations of SCN5A, the gene that encodes the human Na(+)
      channel alpha-subunit, are linked to 1 form of the congenital long-QT syndrome
      (LQT-3). D1790G (DG), an LQT-3 mutation of the C-terminal region of the Na(+)
      channel alpha-subunit, alters steady-state inactivation of expressed channels but
      does not promote sustained Na(+) channel activity. Recently, flecainide, but not
      lidocaine, has been found to correct the disease phenotype, delayed ventricular
      repolarization, in DG carriers. METHODS AND RESULTS: To understand the molecular
      basis of this difference, we studied both drugs using wild-type (WT) and mutant
      Na(+) channels expressed in HEK 293 cells. The DG mutation conferred a higher
      sensitivity to lidocaine (EC(50), WT=894 and DG=205 micromol/L) but not
      flecainide tonic block in a concentration range that is not clinically relevant.
      In contrast, in a concentration range that is therapeutically relevant, DG
      channels are blocked selectively by flecainide (EC(50), WT=11.0 and DG=1.7
      micromol/L), but not lidocaine (EC(50), WT=318.0 and DG=176 micromol/L) during
      repetitive stimulation. CONCLUSIONS: These results (1) demonstrate that the DG
      mutation confers a unique pharmacological response on expressed channels; (2)
      suggest that flecainide use-dependent block of DG channels underlies its
      therapeutic effects in carriers of this gene mutation; and (3) suggest a role of
      the Na(+) channel alpha-subunit C-terminus in the flecainide/channel interaction.

PMID- 10952964
TI  - Perinatal changes in myocardial metabolism in lambs.
AB  - BACKGROUND: Lactate accounts for a third of myocardial oxygen consumption before
      and in the first 2 weeks after birth. It is unknown how the remainder of
      myocardial oxygen is consumed. Glucose is thought to be important before birth,
      whereas long-chain fatty acids (LC-FA) are the prime substrate for the adult.
      However, the ability of the myocardium of the newborn to use LC-FA has been
      doubted. METHODS AND RESULTS: We measured the myocardial metabolism of glucose
      and LC-FA with [U-(13)C]glucose and [1-(13)C]palmitate in chronically
      instrumented fetal and newborn lambs. In fetal lambs, myocardial oxidation of
      glucose was high and that of LC-FA was low. Glucose and LC-FA accounted for 48+/
      4% and 2+/-2% of myocardial oxygen consumption, respectively. In newborn lambs,
      oxidation of glucose decreased, whereas oxidation of LC-FA increased. Glucose and
      LC-FA accounted for 12+/-3% and 83+/-19% of myocardial oxygen consumption. To
      test whether near-term fetal lambs could use LC-FA, we increased the supply of LC
      FA with a fat infusion. In fetal lambs during fat infusion, the oxidation of LC
      FA increased 15-fold. Although the oxidation of LC-FA was still lower than in
      newborn lambs, the contribution to myocardial oxygen consumption (70+/-13%) was
      the same as in newborn lambs. CONCLUSIONS: These data show that glucose and
      lactate account for the majority of myocardial oxygen consumption in fetal lambs,
      whereas in newborn lambs, LC-FA and lactate account for the majority of
      myocardial oxygen consumption. Moreover, we showed that the fetal myocardium can
      use LC-FA as an energy substrate.

PMID- 10952965
TI  - Quo vadis? How should we train cardiologists at the turn of the century?
AB  - BACKGROUND: Cardiovascular medicine is weathering challenges on multiple fronts,
      and the paradigm of cardiovascular fellowship training has changed as a result.
      METHODS AND RESULTS: On the basis of a review of the literature and surveys of
      former trainees, we have evaluated our Cardiovascular Fellowship Program at the
      University of Iowa. We have identified principles fundamental to the training of
      fellows. We extend these principles to propose practical ideas for responding to
      the challenges we face in the rapidly changing landscape of medicine in a new
      millennium. CONCLUSIONS: We have proposed a few principles and numerous concrete,
      practical suggestions that will guide our Cardiovascular Fellowship in the
      future. These ideas may prove useful to other training programs.

PMID- 10952966
TI  - Transition from atrioventricular node reentry tachycardia to atrial fibrillation
      begins in the pulmonary veins.

PMID- 10952967
TI  - Malignant T-wave alternans.

PMID- 10952968
TI  - Molecular link between Sudden Infant Death Syndrome and long-QT syndrome is
      "proof of concept".

PMID- 10952969
TI  - Biological function and site II Ca2+-induced opening of the regulatory domain of
      skeletal troponin C are impaired by invariant site I or II Glu mutations.
AB  - To investigate the roles of site I and II invariant Glu residues 41 and 77 in the
      functional properties and calcium-induced structural opening of skeletal muscle
      troponin C (TnC) regulatory domain, we have replaced them by Ala in intact F29W
      TnC and in wild-type and F29W N domains (TnC residues 1-90). Reconstitution of
      intact E41A/F29W and E77A/F29W mutants into TnC-depleted muscle skinned fibers
      showed that Ca(2+)-induced tension is greatly reduced compared with the F29W
      control. Circular dichroism measurements of wild-type N domain as a function of
      pCa (= -log[Ca(2+)]) demonstrated that approximately 90% of the total change in
      molar ellipticity at 222 nm ([theta](222 nm)) could be assigned to site II Ca(2+)
      binding. With E41A, E77A, and cardiac TnC N domains this [theta](222 nm) change
      attributable to site II was reduced to < or =40% of that seen with wild type,
      consistent with their structures remaining closed in +Ca(2+). Furthermore, the
      Ca(2+)-induced changes in fluorescence, near UV CD, and UV difference spectra
      observed with intact F29W are largely abolished with E41A/F29W and E77A/F29W
      TnCs. Taken together, the data indicate that the major structural change in N
      domain, including the closed to open transition, is triggered by site II Ca(2+)
      binding, an interpretation relevant to the energetics of the skeletal muscle TnC
      and cardiac TnC systems.

PMID- 10952971
TI  - Membrane localization of cyclic nucleotide phosphodiesterase 3 (PDE3). Two N
      terminal domains are required for the efficient targeting to, and association of,
      PDE3 with endoplasmic reticulum.
AB  - Subcellular localization of cyclic nucleotide phosphodiesterases (PDEs) may be
      important in compartmentalization of cAMP/cGMP signaling responses. In 3T3-L1
      adipocytes, mouse (M) PDE3B was associated with the endoplasmic reticulum (ER) as
      indicated by its immunofluorescent colocalization with the ER protein BiP and
      subcellular fractionation studies. In transfected NIH 3006 or COS-7 cells,
      recombinant wild-type PDE3A and PDE3B isoforms were both found almost exclusively
      in the ER. The N-terminal portion of PDE3 can be arbitrarily divided into region
      1 (aa 1-300), which contains a large hydrophobic domain with six predicted
      transmembrane helices, followed by region 2 (aa 301-500) containing a smaller
      hydrophobic domain (of approximately 50 aa). To investigate the role of regions 1
      and 2 in membrane association, we examined the subcellular localization of a
      series of catalytically active, Flag-tagged N-terminal-truncated human (H) PDE3A
      and MPDE3B recombinants, as well as a series of fragments from regions 1 and 2 of
      MPDE3B synthesized as enhanced green fluorescent (EGFP) fusion proteins in COS-7
      cells. In COS-7 cells, the localization of a mutant HPDE3A, lacking the first 189
      amino acids (aa) and therefore four of the six predicted transmembrane helices
      (H3A-Delta189), was virtually identical to that of the wild type. M3B-Delta302
      (lacking region 1) and H3A-Delta397 (lacking region 1 as well as part of region
      2) retained, to different degrees, the ability to associate with membranes,
      albeit less efficiently than H3A-Delta189. Proteins that lacked both regions 1
      and 2, H3A-Delta510 and M3B-Delta604, did not associate with membranes.
      Consistent with these findings, region 1 EGFP-MPDE3B fusion proteins colocalized
      with the ER, whereas region 2 EGFP fusion proteins were diffusely distributed.
      Thus, some portion of the N-terminal hydrophobic domain in region 1 plus a second
      domain in region 2 are important for efficient membrane association/targeting of
      PDE3.

PMID- 10952972
TI  - Two residues in the T-loop of GlnK determine NifL-dependent nitrogen control of
      nif gene expression.
AB  - X-ray crystallographic analysis of the Escherichia coli P(II) protein paralogues
      GlnB and GlnK has shown that they share a superimposable structural core but can
      differ in conformation of the T-loop, a region of the protein (residues 37-54)
      that has been shown to be important for interaction with other proteins. In
      Klebsiella pneumoniae GlnK has been shown to have a clearly defined function in
      regulating NifL-mediated inhibition of NifA activity in response to the nitrogen
      status, and GlnB, when expressed from the chromosome, does not substitute for
      GlnK. Because the T-loops of K. pneumoniae and E. coli GlnB and GlnK differ at
      just three residues, 43, 52, and 54, we have used a previously constructed
      heterologous system, in which K. pneumoniae nifLA is expressed in E. coli, to
      investigate the importance of GlnK residues 43, 52, and 54 for regulation of the
      NifLA interaction. By site-directed mutagenesis of glnB we have shown that
      residue 54 is the single most important amino acid in the T-loop in the context
      of the regulation of NifA activity. Furthermore, a combination of just two
      changes, in residues 54 and 43, allows GlnB to function as GlnK and completely
      relieve NifL inhibition of NifA activity.

PMID- 10952970
TI  - Activation and active site occupation alter conformation in the region of the
      first epidermal growth factor-like domain of human factor VII.
AB  - The first epidermal growth factor-like domain (EGF-1) of factor VII (FVII)
      provides the region of greatest contact during the interaction of FVIIa with
      tissue factor. To understand this interaction better, the conformation-sensitive
      FVII EGF-1-specific monoclonal antibody (mAb) 231-7 was used to investigate the
      conformational effects occurring in this region upon both FVII activation and
      active site occupation. The binding affinity of mAb 231-7 was approximately 3
      fold greater for the zymogen state than for the active state; a result affected
      by the presence of both calcium and the adjacent Gla domain. Once activated,
      active site inhibition of FVIIa with a variety of chloromethyl ketone inhibitors
      resulted in a 10-fold range of affinities of FVIIai molecules to mAb 231-7. Gla
      domain removal eliminated this variation in affinity, suggesting the involvement
      of a Gla/EGF-1 interaction in this conformational effect. In addition, the
      binding of mAb 231-7 to FVIIa EGF-1 stimulated the amidolytic activity of free
      FVIIa. Taken together, these results imply an allosteric interaction between the
      FVIIa active site and the EGF-1 domain that is sensitive to variation in active
      site occupant structure. Thus, these present studies indicate that the
      conformational change associated with FVII activation and active site occupation
      involves the EGF-1 domain and suggest potential functional consequences of these
      changes.

PMID- 10952973
TI  - Acidic amino acids flanking phosphorylation sites in the M2 muscarinic receptor
      regulate receptor phosphorylation, internalization, and interaction with
      arrestins.
AB  - The studies reported here address the molecular events underlying the
      interactions of arrestins with the M(2) muscarinic acetylcholine receptor
      (mAChR). In particular, we focused on the role of receptor phosphorylation in
      this process. Agonist-dependent phosphorylation of the M(2) mAChR can occur at
      clusters of serines and threonines at positions 286-290 (site P1) or 307-311
      (site P2) in the third intracellular loop (Pals-Rylaarsdam, R., and Hosey, M. M.
      (1997) J. Biol. Chem. 272, 14152-14158). Phosphorylation at either P1 or P2 can
      support agonist-dependent internalization. However, phosphorylation at P2 is
      required for receptor interaction with arrestins (Pals-Rylaarsdam, R., Gurevich,
      V. V., Lee, K. B., Ptasienski, J. A., Benovic, J. L., and Hosey, M. M. (1997) J.
      Biol. Chem. 272, 23682-26389). The present study investigated the role of acidic
      amino acids between P1 and P2 in regulating receptor phosphorylation,
      internalization, and receptor/arrestin interactions. Mutation of the acidic amino
      acids at positions 298-300 (site A1) and/or 304-305 (site A2) to alanines had
      significant effects on agonist-dependent phosphorylation. P2 was identified as
      the preferred site of agonist-dependent phosphorylation, and full phosphorylation
      at P2 required the acidic amino acids at A1 or their neutral counterparts. In
      contrast, phosphorylation at site P1 was dependent on site A2. In addition, sites
      A1 and A2 significantly affected the ability of the wild type and P1 and P2
      mutant receptors to internalization and to interact with arrestin2. Substitution
      of asparagine and glutamine for the aspartates and glutamates at sites A1 or A2
      did not influence receptor phosphorylation but did influence arrestin interaction
      with the receptor. We propose that the amino acids at sites A1 and A2 play
      important roles in agonist-dependent phosphorylation at sites P2 and P1,
      respectively, and also play an important role in arrestin interactions with the
      M(2) mAChR.

PMID- 10952974
TI  - Eicosanoid activation of extracellular signal-regulated kinase1/2 in human
      epidermoid carcinoma cells.
AB  - 12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE), a 12-lipoxygenase metabolite of
      arachidonic acid, has multiple effects on tumor and endothelial cells, including
      stimulation of invasion and angiogenesis. However, the signaling mechanisms
      controlling these physiological processes are poorly understood. In a human
      epidermoid carcinoma cell line (i.e. A431), 12(S)-HETE activates extracellular
      signal-regulated kinases 1/2 (ERK1/2), which is mediated by upstream kinases MEK
      and Raf. 12(S)-HETE stimulates phosphorylation of phospholipase Cgamma1 and
      activity of protein kinase Calpha (PKCalpha). In addition, independent of PKC
      12(S)-HETE increases tyrosine phosphorylation of Shc, and Grb2, stimulates
      association between Shc and Src, and increases the activity of Ras, via Src
      family kinases. Furthermore, at low (10-100 nm) concentrations 12(S)-HETE
      counteracts epidermal growth factor-stimulated activation of ERK1/2 via
      stimulating protein tyrosine phosphatases. We also present evidence that 12(S)
      HETE stimulates ERK1/2 via G proteins and that A431 cells have multiple binding
      sites for 12(S)-HETE. Finally, inhibition of 12-lipoxygenase induced apoptosis of
      A431 cells, which was reversed by addition of exogenous 12(S)-HETE. Collectively
      we demonstrate that the activation of ERK1/2 by 12(S)-HETE may be regulated by
      multiple receptors triggering PKC-dependent and PKC-independent pathways in A431
      cells.

PMID- 10952975
TI  - Identification of the hyaluronan receptor for endocytosis (HARE).
AB  - Rat liver sinusoidal endothelial cells (LECs) express two hyaluronan (HA)
      receptors, of 175 and 300 kDa, responsible for the endocytic clearance of HA. We
      have characterized eight monoclonal antibodies (mAbs) raised against the 175-kDa
      HA receptor partially purified from rat LECs. These mAbs also cross-react with
      the 300-kDa HA receptor. The 175-kDa HA receptor is a single protein, whereas the
      300-kDa species contains three subunits, alpha, beta, and gamma at 260, 230, and
      97 kDa, respectively (Zhou, B., Oka, J. A., and Weigel, P. H. (1999) J. Biol.
      Chem. 274, 33831-33834). The 97-kDa subunit was not recognized by any of the mAbs
      in Western blots. Based on their cross-reactivity with these mAbs, the 175-, 230
      , and 260-kDa proteins appear to be related. Two of the mAbs inhibit (125)I-HA
      binding and endocytosis by LECs at 37 degrees C. All of these results confirm
      that the mAbs recognize the bone fide LEC HA receptor. Indirect immunofluoresence
      shows high protein expression in liver sinusoids, the venous sinuses of the red
      pulp in spleen, and the medullary sinuses of lymph nodes. Because the tissue
      distribution for this endocytic HA receptor is not unique to liver, we propose
      the name HARE (HA receptor for endocytosis).

PMID- 10952976
TI  - Thrombin is a potent inducer of connective tissue growth factor production via
      proteolytic activation of protease-activated receptor-1.
AB  - The coagulation protease thrombin plays a critical role in hemostasis and exerts
      pro-inflammatory and pro-fibrotic effects via proteolytic activation of the major
      thrombin receptor, protease-activated receptor-1 (PAR-1). Connective tissue
      growth factor (CTGF) is a novel fibroblast mitogen and also promotes
      extracellular matrix protein production. It is selectively induced by
      transforming growth factor beta (TGF-beta) and is thought to be the autocrine
      agent responsible for mediating its pro-fibrotic effects. CTGF is up-regulated
      during tissue repair and in fibrotic conditions associated with activation of the
      coagulation cascade. We therefore hypothesized that coagulation proteases promote
      the production of CTGF by cells at sites of tissue injury. To begin to address
      this hypothesis, we assessed the effect of coagulation proteases on fibroblast
      CTGF expression in vitro, and we show that thrombin, at physiological
      concentrations, up-regulated CTGF mRNA levels 5-fold relative to base line (p <
      0.01) in fetal fibroblasts and 7-fold in primary adult fibroblasts (p < 0.01).
      These effects were cycloheximide-insensitive and were not blocked with a pan
      specific TGF-beta-neutralizing antibody. They were further paralleled by a
      concomitant increase in CTGF protein production and could be mimicked with
      selective PAR-1 agonists. In addition, fibroblasts derived from PAR-1 knockout
      mice were unresponsive to thrombin but responded normally to TGF-beta(1).
      Finally, factor Xa, which is responsible for activating prothrombin during blood
      coagulation, exerted similar stimulatory effects. We propose that coagulation
      proteases and PAR-1 may play a role in promoting connective tissue formation
      during normal tissue repair and the development of fibrosis by up-regulating
      fibroblast CTGF expression.

PMID- 10952977
TI  - An early ethylene up-regulated gene encoding a calmodulin-binding protein
      involved in plant senescence and death.
AB  - 35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A
      positive clone (NtER1) with high homology to an early ethylene-up-regulated gene
      (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized.
      Based on the helical wheel projection, a 25-mer peptide corresponding to the
      predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The
      gel-mobility shift assay showed that the peptide formed a stable complex with CaM
      only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d)
      approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different
      stages of development were treated with ethylene or with 1-methylcyclopropene for
      2 h before treating with ethylene. Northern analysis showed that the NtER1 was
      rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1
      methylcyclopropene treatment totally blocked NtER1 expression in flowers at all
      stages of development, suggesting that NtER1 is an early ethylene-up-regulated
      gene. The senescing leaves and petals had significantly increased NtER1 induction
      as compared with young leaves and petals, implying that NtER1 is developmentally
      regulated and acts as a trigger for senescence and death. This is the first
      documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in
      ethylene action.

PMID- 10952978
TI  - Thermodynamic study of ligand binding to protein-tyrosine phosphatase 1B and its
      substrate-trapping mutants.
AB  - The binding of several phosphonodifluoromethyl phenylalanine (F(2)Pmp)-containing
      peptides to protein-tyrosine phosphatase 1B (PTP1B) and its substrate-trapping
      mutants (C215S and D181A) has been studied using isothermal titration
      calorimetry. The binding of a high affinity ligand, Ac-Asp-Ala-Asp-Glu-F(2)Pmp
      Leu-NH(2), to PTP1B (K(d) = 0.24 microm) is favored by both enthalpic and
      entropic contributions. Disruption of ionic interactions between the side chain
      of Arg-47 and the N-terminal acidic residues reduces the binding affinity
      primarily through the reduction of the TDeltaS term. The role of Arg-47 may be to
      maximize surface contact between PTP1B and the peptide, which contributes to high
      affinity binding. The active site Cys-215 --> Ser mutant PTP1B binds ligands with
      the same affinity as the wild-type enzyme. However, unlike wild-type PTP1B,
      peptide binding to C215S is predominantly driven by enthalpy change, which likely
      results from the elimination of the electrostatic repulsion between the thiolate
      anion and the phosphonate group. The increased enthalpic contribution is offset
      by reduction in the binding entropy, which may be the result of increased entropy
      of the unbound protein caused by this mutation. The general acid-deficient mutant
      D181A binds the peptide 5-fold tighter than the C215S mutant, consistent with the
      observation that the Asp to Ala mutant is a better "substrate-trapping" reagent
      than C215S. The increased binding affinity for D181A as compared with the wild
      type PTP1B results primarily from an increase in the DeltaH of binding in the
      mutant, which may be related to decreased electrostatic repulsion between the
      phosphate moiety and PTP1B. These results have important implications for the
      design of high affinity PTP1B inhibitors.

PMID- 10952979
TI  - Phorbol ester-regulated cleavage of normal prion protein in HEK293 human cells
      and murine neurons.
AB  - Cellular prion protein (PrP(c)) undergoes a proteolytic attack at the 110/111
      downward arrow112 peptide bond, whereas the PrP isoform (PrP(res)) that
      accumulates in the brain tissue in Creutzfeldt-Jakob disease reveals an alternate
      cleavage site at about residue 90. Interestingly, the normal processing of PrP
      occurs inside the 106-126 amino acid region thought to be responsible for the
      neurotoxicity of the pathogenic prions, whereas PrP(res) cleavage preserves this
      potentially toxic domain. Therefore, any molecular mechanisms leading to enhanced
      cleavage at the 110/111 downward arrow112 peptide bond could be of potential
      interest. We set up TSM1 neurons and HEK293 stable transfectants overexpressing
      the wild-type or 3F4-tagged murine PrP(c), respectively. Both mock-transfected
      and PrP(c)-expressing cell lines produced an 11-12-kDa PrP fragment (referred to
      as N1), the immunological characterization of which strongly suggests that it
      corresponds to the N-terminal PrP(c) fragment derived from normal processing. We
      have established that the recovery of secreted N1 is increased by the protein
      kinase C agonists PDBu and PMA in a time- and dose-dependent manner in both cell
      lines. In contrast, secretion of N1 remains unaffected by the inactive PDBu
      analog alphaPDD and by the protein kinase A effectors dibutyryl cAMP and
      forskolin. Overall, our data indicate that the normal processing of PrP(c) is up
      regulated by protein kinase C but not protein kinase A in human cells and murine
      neurons.

PMID- 10952980
TI  - Interaction of human alpha-Synuclein and Parkinson's disease variants with
      phospholipids. Structural analysis using site-directed mutagenesis.
AB  - alpha-Synuclein has been centrally implicated in neurodegenerative disease, and a
      normal function in developmental synaptic plasticity has been suggested by
      studies in songbirds. A variety of observations suggest the protein partitions
      between membrane and cytosol, a behavior apparently conferred by a conserved
      structural similarity to the exchangeable apolipoproteins. Here we show that the
      capacity to bind lipids is broadly distributed across exons 3, 4, and 5 (encoding
      residues 1-102). Binding to phosphatidylserine-containing vesicles requires the
      presence of all three exons, while binding to phosphatidic acid can be mediated
      by any one of the three. Consistent with a "class A2" helical binding mechanism,
      lipid association is disrupted by introduction of charged residues along the
      hydrophobic face of the predicted alpha-helix and also by biotinylation of
      conserved lysines (which line the interfacial region). Circular dichroism
      spectroscopy reveals a general correlation between the amount of lipid-induced
      alpha-helix content and the degree of binding to PS-containing vesicles. Two
      point mutations associated with Parkinson's disease have little (A30P) or no
      (A53T) effect on lipid binding or alpha-helicity. These results are consistent
      with the hypothesis that alpha-synuclein's normal functions depend on an ability
      to undergo a large conformational change in the presence of specific
      phospholipids.

PMID- 10952981
TI  - Sustained expression of exendin-4 does not perturb glucose homeostasis, beta-cell
      mass, or food intake in metallothionein-preproexendin transgenic mice.
AB  - Activation of glucagon-like peptide (GLP)-1 receptor signaling promotes glucose
      lowering via multiple mechanisms, including regulation of food intake, glucose
      dependent insulin secretion, and stimulation of beta-cell mass. As GLP-1 exhibits
      a short t(12) in vivo, the biological consequences of prolonged GLP-1 receptor
      signaling remains unclear. To address this question, we have now generated
      metallothionein promoter-preproexendin (MT-Ex) transgenic mice. MT-Ex mice
      process preproexendin correctly, as is made evident by detection of circulating
      plasma exendin-4 immunoreactivity using high pressure liquid chromatography and
      an exendin-4-specific radioimmunoassay. Despite elevated levels of exendin-4,
      fasting plasma glucose and glucose clearance following oral and intraperitoneal
      glucose tolerance tests are normal in MT-Ex mice. Induction of transgene
      expression significantly reduced glycemic excursion during both oral and
      intraperitoneal glucose tolerance tests (p < 0.05) and increased levels of
      glucose-stimulated insulin following oral glucose administration (p < 0.05).
      Despite evidence that exendin-4 may induce beta-cell proliferation, beta-cell
      mass and islet histology were normal in MT-Ex mice. MT-Ex mice exhibited no
      differences in basal food intake or body weight; however, induction of exendin-4
      expression was associated with reduced short term food ingestion (p < 0.05). In
      contrast, short term water intake was significantly reduced in the absence of
      zinc in fluid-restricted MT-Ex mice (p < 0.05). These findings illustrate that
      sustained elevation of circulating exendin-4 is not invariably associated with
      changes in glucose homeostasis, increased beta-cell mass, or reduction in food
      intake in mice in vivo.

PMID- 10952982
TI  - 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase (WaaA) and kdo kinase
      (KdkA) of Haemophilus influenzae are both required to complement a waaA knockout
      mutation of Escherichia coli.
AB  - The lipopolysaccharide (LPS) of the deep rough mutant Haemophilus influenzae I69
      consists of lipid A and a single 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo)
      residue substituted with one phosphate at position 4 or 5 (Helander, I. M.,
      Lindner, B., Brade, H., Altmann, K., Lindberg, A. A., Rietschel, E. T., and
      Zahringer, U. (1988) Eur. J. Biochem. 177, 483-492). The waaA gene encoding the
      essential LPS-specific Kdo transferase was cloned from this strain, and its
      nucleotide sequence was identical to H. influenzae DSM11121. The gene was
      expressed in the Gram-positive host Corynebacterium glutamicum and characterized
      in vitro to encode a monofunctional Kdo transferase. waaA of H. influenzae could
      not complement a knockout mutation in the corresponding gene of an Re-type
      Escherichia coli strain. However, complementation was possible by coexpressing
      the recombinant waaA together with the LPS-specific Kdo kinase gene (kdkA) of H.
      influenzae DSM11121 or I69, respectively. The sequences of both kdkA genes were
      determined and differed in 25 nucleotides, giving rise to six amino acid
      exchanges between the deduced proteins. Both E. coli strains which expressed waaA
      and kdkA from H. influenzae synthesized an LPS containing a single Kdo residue
      that was exclusively phosphorylated at position 4. The structure was determined
      by nuclear magnetic resonance spectroscopy of deacylated LPS. Therefore, the
      reaction products of both cloned Kdo kinases represent only one of the two
      chemical structures synthesized by H. influenzae I69.

PMID- 10952983
TI  - Rac1 regulates stress-induced, redox-dependent heat shock factor activation.
AB  - The signaling pathway by which environmental stresses activate heat shock factors
      (HSFs) is not completely understood. We show that the small GTPase rac1, and Rac1
      regulated reactive oxygen species (ROS) play an important role in stress
      stimulated heat shock response. A dominant-negative allele of Rac1 (Rac1N17)
      inhibits the hypoxia/reoxygenation and sodium arsenite-induced transcriptional
      activity of HSF-1 and the transcription of heat shock protein 70. Rac1N17 also
      suppresses the production of intracellular ROS induced by hypoxia/reoxygenation
      or sodium arsenite. Moreover, direct suppression of intracellular ROS levels by
      antioxidants decreases stress-stimulated HSF activity. However, expression of a
      constitutively active mutant of Rac1 (Rac1V12) in the absence of extracellular
      stresses does not increase intracellular ROS levels or induce the heat shock
      response. These results show that Rac1 is a necessary but insufficient component
      of the stress-induced signaling pathway that leads to ROS production, activation
      of HSFs, and transcription of heat shock proteins.

PMID- 10952984
TI  - Tyrosine phosphorylation of cortactin is required for H2O2-mediated injury of
      human endothelial cells.
AB  - Injury of endothelial cells induced by reactive oxygen species plays an important
      role in the development of early stages of vascular diseases such as hypertension
      and atherosclerosis. Exposure of human umbilical vein endothelial cells to
      hydrogen peroxide (H(2)O(2)), a common form of reaction oxygen species, triggers
      a series of intracellular events, including actin cytoskeletal reorganization,
      cytoplasm shrinkage, membrane blebbing and protein-tyrosine phosphorylation. The
      effect of H(2)O(2) on endothelial cells is dramatically enhanced when a survival
      pathway involving extracellular signal-regulated kinase is blocked by PD098059.
      In contrast, the injury of endothelial cells mediated by H(2)O(2) is inhibited by
      PP2, a selective specific inhibitor for protein-tyrosine kinase Src. Cortactin, a
      filamentous actin (F-actin)-associated protein, becomes phosphorylated at
      tyrosine residues upon stimulation by H(2)O(2) in a manner dependent on the
      activity of Src. The level of tyrosine phosphorylation of cortactin is correlated
      with the formation of membrane blebs. Overexpression of wild-type cortactin
      tagged with green fluorescent protein in endothelial cells via a retroviral
      vector substantiates the H(2)O(2)-induced morphological changes, whereas
      overexpression of a green fluorescent protein-cortactin mutant deficient in
      tyrosine phosphorylation renders endothelial cells resistant to H(2)O(2). The
      functional role of cortactin in H(2)O(2)-mediated shape changes was also
      evaluated in NIH 3T3 cells. Stable 3T3 transfectants expressing wild-type
      cortactin in the presence of either H(2)O(2)/PD098059 or H(2)O(2) alone at 200
      microm exhibited a dramatic shape change characterized by rounding up or
      aggregation. However, the similar changes were not detected with cells
      overexpressing a cortactin mutant deficient in tyrosine phosphorylation. These
      data demonstrate an important role of the Src/cortactin-dependent actin
      reorganization in the injury of endothelial cells mediated by reactive oxygen
      species.

PMID- 10952985
TI  - Genetic mapping of the human C5a receptor. Identification of transmembrane amino
      acids critical for receptor function.
AB  - Many hormones and sensory stimuli signal through a superfamily of seven
      transmembrane-spanning receptors to activate heterotrimeric G proteins. How the
      seven transmembrane segments of the receptors (a molecular architecture of
      bundled alpha-helices conserved from yeast to man) work as "on/off" switches
      remains unknown. Previously, we used random saturation mutagenesis coupled with a
      genetic selection in yeast to determine the relative importance of amino acids in
      four of the seven transmembrane segments of the human C5a receptor (Baranski, T.
      J., Herzmark, P., Lichtarge, O., Gerber, B. O., Trueheart, J., Meng, E. C., Iiri,
      T., Sheikh, S. P., and Bourne, H. R. (1999) J. Biol. Chem. 274, 15757-15765). In
      this study, we evaluate helices I, II, and IV, thereby furnishing a complete
      mutational map of the seven transmembrane helices of the human C5a receptor. Our
      analysis identified 19 amino acid positions resistant to non-conservative
      substitutions. When combined with the 25 essential residues previously identified
      in helices III and V-VII, they delineate two distinct components of the receptor
      switch: a ligand-binding surface at or near the extracellular surface of the
      helix bundle and a core cluster in the cytoplasmic half of the bundle. In
      addition, we found critical amino acids in the first and second helices that are
      predicted to face the lipid membrane. These residues form an extended surface
      that might mediate interactions with lipids and other membrane proteins or
      function as an oligomerization domain with other receptors.

PMID- 10952986
TI  - Phosphorylation of geranyl and farnesyl pyrophosphates by Nm23
      proteins/nucleoside diphosphate kinases.
AB  - The biochemical mechanism(s) by which Nm23 proteins/nucleoside diphosphate
      kinases suppress tumor metastasis, inhibit cell motility, and affect cellular
      differentiation are not known. Here we report that Nm23 proteins can
      phosphorylate geranyl and farnesyl pyrophosphates to give triphosphates. Wild
      type Nm23-H1 had higher geranyl and farnesyl pyrophosphate kinase activities than
      did mutants of Nm23-H1 that do not inhibit cell motility. The phosphorylation of
      farnesyl pyrophosphate appears to occur in vivo as cells with an elevated level
      of Nm23-H1 contained more farnesyl triphosphate than did control cells. To our
      knowledge, this is the first report that farnesyl triphosphate exists in cells.
      The phosphorylation of farnesyl pyrophosphate by Nm23 proteins could alter
      isoprenoid metabolism, and cells with an elevated level of Nm23 proteins were
      found to contain more farnesylated 46- and 24-kDa proteins than did control
      cells. The phosphorylation of geranyl and farnesyl pyrophosphates by Nm23
      proteins provides a novel mechanism by which these proteins might exert their
      biological effects.

PMID- 10952987
TI  - The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and
      mitochondrial enzymes by means of an unusual alternative splicing of the primary
      transcript.
AB  - Two cDNAs encoding human lysyl-tRNA synthetase have been identified. One encodes
      the cytoplasmic form of the enzyme identified previously. The second cDNA
      contains the same sequence but with a 180-bp insertion at the 5'-end of the mRNA.
      This results in a predicted protein whose carboxyl 576 amino acids are identical
      to those of the cytoplasmic enzyme but with a different amino terminus of 49
      amino acids that contains a putative mitochondrial targeting sequence. Expression
      of the two lysyl-tRNA synthetase-green fluorescent protein gene fusions in a
      human cell line confirmed that the cytoplasmic form was targeted to the cytoplasm
      and the mitochondrial form to mitochondria. The genomic lysyl-tRNA synthetase
      gene consisted of 15 exons. The two isoforms were created by alternative splicing
      of the first three exons of the gene. The cytoplasmic form was created by
      splicing exon 1 to exon 3. The inclusion of exon 2 between exons 1 and 3 produced
      an mRNA encoding the mitochondrial isoform with an additional upstream small open
      reading frame, consisting mainly of a portion of the 5' coding region of the
      cytoplasmic isoform. This is the first example of mitochondrial targeting
      sequence being encoded on the second exon of a gene. Ribonuclease protection
      analysis showed that the mRNA encoding the cytoplasmic isoform makes up
      approximately 70%, and the mitochondrial isoform approximately 30%, of the mature
      transcripts from the lysyl-tRNA synthetase gene. The mitochondrial form of the
      enzyme, purified after expression in Escherichia coli, aminoacylated in vitro
      transcripts corresponding to both the cytoplasmic and mitochondrial tRNA(Lys),
      despite the difference in the discriminator base sequence in the acceptor stems
      of these tRNAs.

PMID- 10952988
TI  - Substrate recognition by the ClpA chaperone component of ClpAP protease.
AB  - ClpA, a member of the Clp/Hsp100 ATPase family, is a molecular chaperone and
      regulatory component of ClpAP protease. We explored the mechanism of protein
      recognition by ClpA using a high affinity substrate, RepA, which is activated for
      DNA binding by ClpA and degraded by ClpAP. By characterizing RepA derivatives
      with N- or C-terminal deletions, we found that the N-terminal portion of RepA is
      required for recognition. More precisely, RepA derivatives lacking the N-terminal
      5 or 10 amino acids are degraded by ClpAP at a rate similar to full-length RepA,
      whereas RepA derivatives lacking 15 or 20 amino acids are degraded much more
      slowly. Thus, ClpA recognizes an N-terminal signal in RepA beginning in the
      vicinity of amino acids 10-15. Moreover, peptides corresponding to RepA amino
      acids 4-13 and 1-15 inhibit interactions between ClpA and RepA. We constructed
      fusions of RepA and green fluorescent protein, a protein not recognized by ClpA,
      and found that the N-terminal 15 amino acids of RepA are sufficient to target the
      fusion protein for degradation by ClpAP. However, fusion proteins containing 46
      or 70 N-terminal amino acids of RepA are degraded more efficiently in vitro and
      are noticeably stabilized in vivo in clpADelta and clpPDelta strains compared
      with wild type.

PMID- 10952989
TI  - Osmotic stress regulates the stability of cyclin D1 in a p38SAPK2-dependent
      manner.
AB  - We report here that different cell stresses regulate the stability of cyclin D1
      protein. Exposition of Granta 519 cells to osmotic shock, oxidative stress, and
      arsenite induced the post-transcriptional down-regulation of cyclin D1. In the
      case of osmotic shock, this effect was completely reversed by the addition of
      p38(SAPK2)-specific inhibitors (SB203580 or SB220025), indicating that this
      effect is dependent on p38(SAPK2) activity. Moreover, the use of proteasome
      inhibitors prevented this down-regulation. Thus, osmotic shock induces
      proteasomal degradation of cyclin D1 protein by a p38(SAPK2)-dependent pathway.
      The effect of p38(SAPK2) on cyclin D1 stability might be mediated by direct
      phosphorylation at specific sites. We found that p38(SAPK2) phosphorylates cyclin
      D1 in vitro at Thr(286) and that this phosphorylation triggers the ubiquitination
      of cyclin D1. These results link for the first time a stress-induced MAP kinase
      pathway to cyclin D1 protein stability, and they will help to understand the
      molecular mechanisms by which stress transduction pathways regulate the cell
      cycle machinery and take control over cell proliferation.

PMID- 10952990
TI  - Tobacco nectarin I. Purification and characterization as a germin-like, manganese
      superoxide dismutase implicated in the defensE of floral reproductive tissues.
AB  - Nectarin I, a protein that accumulates in the nectar of Nicotiana sp. , was
      determined to contain superoxide dismutase activity by colorimetric and in-gel
      assays. This activity was found to be remarkably thermostable. Extended
      incubations at temperatures up to 90 degrees C did not diminish the superoxide
      dismutase activity of nectarin I. This attribute allowed nectarin I to be
      purified to homogeneity by heat denaturation of the other nectar proteins. By SDS
      polyacrylamide gel electrophoresis, nectarin I appeared as a 29-kDa monomer. If
      the protein sample was not boiled prior to loading the gel, then nectarin I
      migrated as 165-kDa oligomeric protein. By matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, the protomer subunit was
      found to be a 22.5-kDa protein. Purified nectarin I contained 0.5 atoms of
      manganese/monomer, and the superoxide dismutase activity of nectarin I was not
      inhibited by either H(2)O(2) or NaCN. Following denaturation, the superoxide
      dismutase activity was restored after Mn(2+) addition. Addition of Fe(2+),
      Cu(2+), Zn(2+), and Cu(2+)/Zn(2+) did not restore superoxide dismutase activity.
      The quaternary structure of the reconstituted enzyme was examined, and only
      tetrameric and pentameric aggregates were enzymatically active. The reconstituted
      enzyme was also shown to generate H(2)O(2). Putative nectarin I homologues were
      found in the nectars of several other plant species.

PMID- 10952991
TI  - Fas- and tumor necrosis factor-mediated apoptosis uses the same binding surface
      of FADD to trigger signal transduction. A typical model for convergent signal
      transduction.
AB  - FADD is known to function as a common signaling conduit in Fas- and tumor
      necrosis factor (TNF)-mediated apoptosis. The convergent death signals from the
      Fas receptor and TNF receptor 1 are transferred to FADD by death domain
      interactions triggering the same cellular event, caspase-8 activation. In this
      work, we investigated whether the same binding surface of FADD is used for both
      signaling pathways by using FADD death domain mutants. Mutations in helices
      alpha2 and alpha3 of the FADD death domain, the interacting surface with the Fas
      death domain, affected TNF-mediated apoptosis to various extents. This indicated
      that TNF-mediated apoptosis uses the same binding surface of the FADD death
      domain as Fas-mediated apoptosis. The binding specificity is not the same,
      however. Some mutations affected the binding affinity of the Fas death domain for
      the FADD death domain, but did not influence TNF-mediated apoptosis and vice
      versa. Interestingly, all mutants tested that affected TNF-mediated apoptosis
      have structural perturbations, implying that the structural integrity, involving
      helices alpha2 and alpha3 in particular, is critical in TNF-mediated apoptosis.
      Our results suggest that different signaling molecules use a similar structural
      interaction to trigger the same cellular event, such as caspase-8 recruitment,
      which could be typical in convergent signal transduction.

PMID- 10952992
TI  - The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for
      selective dimerization and divalent cation-enhanced DNA binding.
AB  - The cAMP responsive element-binding protein (CREB) is central to second messenger
      regulated transcription. To elucidate the structural mechanisms of DNA binding
      and selective dimerization of CREB, we determined to 3.0 A resolution, the
      structure of the CREB bZIP (residues 283-341) bound to a 21-base pair
      deoxynucleotide that encompasses the canonical 8-base pair somatostatin cAMP
      response element (SSCRE). The CREB dimer is stabilized in part by ionic
      interactions from Arg(314) to Glu(319') and Glu(328) to Lys(333') as well as a
      hydrogen bond network that links the carboxamide side chains of Gln(322')
      Asn(321)-Asn(321')-Gln(322). Critical to family selective dimerization are
      intersubunit hydrogen bonds between basic region residue Tyr(307) and leucine
      zipper residue Glu(312), which are conserved in all CREB/CREM/ATF-1 family
      members. Strikingly, the structure reveals a hexahydrated Mg(2+) ion bound in the
      cavity between the basic region and SSCRE that makes a water-mediated DNA
      contact. DNA binding studies demonstrate that Mg(2+) ions enhance CREB bZIP:SSCRE
      binding by more than 25-fold and suggest a possible physiological role for this
      ion in somatostatin cAMP response element and potentially other CRE-mediated gene
      expression.

PMID- 10952993
TI  - The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene.
AB  - Metal regulation of the mouse zinc transporter (ZnT)-1 gene was examined in
      cultured cells and in the developing conceptus. Zinc or cadmium treatment of cell
      lines rapidly (3 h) and dramatically (about 12-fold) induced ZnT1 mRNA levels. In
      cells incubated in medium supplemented with Chelex-treated fetal bovine serum, to
      remove metal ions, levels of ZnT1 mRNA were reduced, and induction of this
      message in response to zinc or cadmium was accentuated (up to 31-fold induction).
      Changes in ZnT1 gene expression in these experiments paralleled those of
      metallothionein I (MT-I). Inhibition of RNA synthesis blocked metal induction of
      ZnT1 and MT-I mRNAs, whereas inhibition of protein synthesis did not. Metal
      response element-binding transcription factor (MTF)-1 mediates metal regulation
      of the metallothionein I gene. In vitro DNA-binding assays demonstrated that
      mouse MTF-1 can bind avidly to the two metal-response element sequences found in
      the ZnT1 promoter. Using mouse embryo fibroblasts with homozygous deletions of
      the MTF-1 gene, it was shown that this transcription factor is essential for
      basal as well as metal (zinc and cadmium) regulation of the ZnT1 gene in these
      cells. In vivo, ZnT1 mRNA was abundant in the midgestation visceral yolk sac and
      placenta. Dietary zinc deficiency during pregnancy down-regulated ZnT1 and MT-I
      mRNA levels (4-5-fold and >20-fold, respectively) in the visceral yolk sac, but
      had little effect on these mRNAs in the placenta. Homozygous knockout of the MTF
      1 gene in transgenic mice also led to a 4-6-fold reduction in ZnT1 mRNA levels
      and a loss of MT-I mRNA in the visceral yolk sac. These results suggest that MTF
      1 mediates the response to metal ions of both the ZnT1 and the MT-I genes the
      visceral yolk sac. Overall, these studies suggest that MTF-1 directly coordinates
      the regulation of genes involved in zinc homeostasis and protection against metal
      toxicity.

PMID- 10952994
TI  - Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as
      determined by activation of NF kappa B and expression of the inducible
      cyclooxygenase.
AB  - Genetic evidence indicating that TOLL-like receptor 4 (Tlr4) is the
      lipopolysaccharide (LPS) receptor in mice was reported. However, biochemical
      evidence that murine Tlr4 confers LPS responsiveness has not been convincingly
      demonstrated. Inducible cyclooxygenase (COX-2) is selectively expressed in LPS
      stimulated macrophages in part mediated through the activation of NF kappa B.
      Thus, we determined whether murine Tlr4 confers LPS responsiveness as evaluated
      by the activation of NF kappa B and COX-2 expression. Transfection of a murine
      macrophage-like cell line (RAW264.7) with the constitutively active form (delta
      Tlr4) of Tlr4 is sufficient to activate NF kappa B and COX-2 expression. However,
      the truncated form (delta Tlr4(P712H)) of the missense mutant Tlr4(P712H) found
      in LPS-hyporesponsive mouse strain (C3H/HeJ) inhibits LPS-induced NF kappa B
      activation and COX-2 expression. The inability of delta Tlr4(P712H) to activate
      NF kappa B and induce COX-2 expression is rescued by a constitutively active
      adapter protein myeloid differentiation factor 88 (MyD88), which interacts
      directly with the cytoplasmic domain of Tlr proteins. Furthermore, MyD88 is co
      immunoprecipitated with the wild-type delta Tlr4 but not with the delta
      Tlr4(P712H) mutant. Together, these results indicate that Tlr4 confers LPS
      responsiveness in RAW264.7 cells and suggest that hyporesponsiveness of C3H/HeJ
      mice to LPS is attributed to the disruption of Tlr4-mediated signaling pathways
      that results from the inability of the mutant Tlr4(P712H) to interact with MyD88.

PMID- 10952995
TI  - Skeletal muscle ryanodine receptor is a redox sensor with a well defined redox
      potential that is sensitive to channel modulators.
AB  - Hyperreactive sulfhydryl groups associated with the Ca(2+) release protein from
      sarcoplasmic reticulum are shown to have a well defined reduction potential that
      is sensitive to the cellular environment. Ca(2+) channel activators lower the
      redox potential of the ryanodine receptor, which favors the oxidation of thiols
      and the opening of the Ca(2+) release protein. In contrast, channel inhibitors
      increase the redox potential, which favors the reduction of disulfides and the
      closure of the release protein. Modulation of redox potential of reactive thiols
      may be a general control mechanism by which sarcoplasmic/endoplasmic reticulum,
      ryanodine receptors/IP(3) receptors, control cytoplasmic Ca(2+) concentrations.

PMID- 10952996
TI  - Binding of the Mex67p/Mtr2p heterodimer to FXFG, GLFG, and FG repeat nucleoporins
      is essential for nuclear mRNA export.
AB  - It is not known how Mex67p and Mtr2p, which form a heterodimer essential for mRNA
      export, transport mRNPs through the nuclear pore. Here, we show that the
      Mex67p/Mtr2p complex binds to all of the repeat types (GLFG, FXFG, and FG) found
      in nucleoporins. For this interaction, complex formation between Mex67p and Mtr2p
      has to occur. MEX67 and MTR2 also genetically interact with different types of
      repeat nucleoporins, such as Nup116p, Nup159p, Nsp1p, and Rip1p/Nup40p. These
      data suggest a model in which nuclear mRNA export requires the Mex67p/Mtr2p
      heterodimeric complex to directly contact several repeat nucleoporins, organized
      in different nuclear pore complex subcomplexes, as it carries the mRNP cargo
      through the nuclear pore.

PMID- 10952997
TI  - Conserved SR protein kinase functions in nuclear import and its action is
      counteracted by arginine methylation in Saccharomyces cerevisiae.
AB  - Mammalian serine and arginine-rich (SR) proteins play important roles in both
      constitutive and regulated splicing, and SR protein-specific kinases (SRPKs) are
      conserved from humans to yeast. Here, we demonstrate a novel function of the
      single conserved SR protein kinase Sky1p in nuclear import in budding yeast. The
      yeast SR-like protein Npl3p is known to enter the nucleus through a composite
      nuclear localization signal (NLS) consisting of a repetitive arginine- glycine
      glycine (RGG) motif and a nonrepetitive sequence. We found that the latter is the
      site for phosphorylation by Sky1p and that this phosphorylation regulates nuclear
      import of Npl3p by modulating the interaction of the RGG motif with its nuclear
      import receptor Mtr10p. The RGG motif is also methylated on arginine residues,
      but methylation does not affect the Npl3p-Mtr10p interaction in vitro.
      Remarkably, arginine methylation interferes with Sky1p-mediated phosphorylation,
      thereby indirectly influencing the Npl3p-Mtr10p interaction in vivo and
      negatively regulating nuclear import of Npl3p. These results suggest that nuclear
      import of Npl3p is coordinately influenced by methylation and phosphorylation in
      budding yeast, which may represent conserved components in the dynamic regulation
      of RNA processing in higher eukaryotic cells.

PMID- 10952998
TI  - Membrane topogenesis of a type I signal-anchor protein, mouse synaptotagmin II,
      on the endoplasmic reticulum.
AB  - Synaptotagmin II is a type I signal-anchor protein, in which the NH(2)-terminal
      domain of 60 residues (N-domain) is located within the lumenal space of the
      membrane and the following hydrophobic region (H-region) shows transmembrane
      topology. We explored the early steps of cotranslational integration of this
      molecule on the endoplasmic reticulum membrane and demonstrated the following:
      (a) The translocation of the N-domain occurs immediately after the H-region and
      the successive positively charged residues emerge from the ribosome. (b)
      Positively charged residues that follow the H-region are essential for
      maintaining the correct topology. (c) It is possible to dissect the lengths of
      the nascent polypeptide chains which are required for ER targeting of the
      ribosome and for translocation of the N-domain, thereby demonstrating that
      different nascent polypeptide chain lengths are required for membrane targeting
      and N-domain translocation. (d) The H-region is sufficiently long for membrane
      integration. (e) Proline residues preceding H-region are critical for N-domain
      translocation, but not for ER targeting. The proline can be replaced with amino
      acid with low helical propensity.

PMID- 10952999
TI  - Changes in endoplasmic reticulum luminal environment affect cell sensitivity to
      apoptosis.
AB  - To test the role of ER luminal environment in apoptosis, we generated HeLa cell
      lines inducible with respect to calreticulin and calnexin and investigated their
      sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER
      luminal protein, resulted in an increased sensitivity of the cells to both
      thapsigargin- and staurosporine-induced apoptosis. This correlated with an
      increased release of cytochrome c from the mitochondria. Overexpression of
      calnexin, an integral ER membrane protein, had no significant effect on drug
      induced apoptosis. In contrast, calreticulin-deficient cells were significantly
      resistant to apoptosis and this resistance correlated with a decreased release of
      cytochrome c from mitochondria and low levels of caspase 3 activity. This work
      indicates that changes in the lumen of the ER amplify the release of cytochrome c
      from mitochondria, and increase caspase activity, during drug-induced apoptosis.
      There may be communication between the ER and mitochondria, which may involve
      Ca(2+) and play an important role in conferring cell sensitivity to apoptosis.
      Apoptosis may depend on both the presence of external apoptosis-activating
      signals, and, as shown in this study, on an internal factor represented by the
      ER.

PMID- 10953000
TI  - Death commitment point is advanced by axotomy in sympathetic neurons.
AB  - Axotomized neurons have several characteristics that are different from intact
      neurons. Here we show that, unlike established cultures, the axotomized
      sympathetic neurons deprived of NGF become committed to die before caspase
      activation, since the same proportion of NGF-deprived neurons are rescued by NGF
      regardless of whether caspases are inhibited by the pan-caspase inhibitor Boc
      Asp(O-methyl)-CH(2)F (BAF). Despite prolonged Akt and ERK signaling induced by
      NGF after BAF treatment has prevented death, the neurons fail to increase protein
      synthesis, recover ATP levels, or grow. Within 3 d, all the mitochondria
      disappear without apparent removal of any other organelles or loss of membrane
      integrity. Although NGF does rescue intact BAF-treated 6-d cultures after NGF
      deprivation, rescue by NGF fails when these neurons are axotomized before NGF
      deprivation and BAF treatment. Moreover, cytosolic cytochrome c rapidly kills
      axotomized neurons. We propose that axotomy induces signals that make sympathetic
      neurons competent to die prematurely. NGF cannot repair these NGF-deprived, BAF
      treated neurons because receptor signaling (which is normal) is uncoupled from
      protein renewal, and the mitochondria (which are damaged) go on to be eliminated.
      Hence, the order of steps underlying neuronal death commitment is mutable and
      open to regulation.

PMID- 10953001
TI  - Biogenesis of the protein storage vacuole crystalloid.
AB  - We identify new organelles associated with the vacuolar system in plant cells.
      These organelles are defined biochemically by their internal content of three
      integral membrane proteins: a chimeric reporter protein that moves there directly
      from the ER; a specific tonoplast intrinsic protein; and a novel receptor-like
      RING-H2 protein that traffics through the Golgi apparatus. Highly conserved
      homologues of the latter are expressed in animal cells. In a developmentally
      regulated manner, the organelles are taken up into vacuoles where, in seed
      protein storage vacuoles, they form a membrane-containing crystalloid. The uptake
      and preservation of the contents of these organelles in vacuoles represents a
      unique mechanism for compartmentalization of protein and lipid for storage.

PMID- 10953002
TI  - Regulation of microtubule dynamics and myogenic differentiation by MURF, a
      striated muscle RING-finger protein.
AB  - The RING-finger domain is a novel zinc-binding Cys-His protein motif found in a
      growing number of proteins involved in signal transduction, ubiquitination, gene
      transcription, differentiation, and morphogenesis. We describe a novel muscle
      specific RING-finger protein (MURF) expressed specifically in cardiac and
      skeletal muscle cells throughout pre- and postnatal mouse development. MURF
      belongs to the RING-B-box-coiled-coil subclass of RING-finger proteins,
      characterized by an NH(2)-terminal RING-finger followed by a zinc-finger domain
      (B-box) and a leucine-rich coiled-coil domain. Expression of MURF is required for
      skeletal myoblast differentiation and myotube fusion. The leucine-rich coiled
      coil domain of MURF mediates association with microtubules, whereas the RING
      finger domain is required for microtubule stabilization and an additional region
      is required for homo-oligomerization. Expression of MURF establishes a cellular
      microtubule network that is resistant to microtubule depolymerization induced by
      alkaloids, cold and calcium. These results identify MURF as a myogenic regulator
      of the microtubule network of striated muscle cells and reveal a link between
      microtubule organization and myogenesis.

PMID- 10953003
TI  - Two pathways through Cdc42 couple the N-formyl receptor to actin nucleation in
      permeabilized human neutrophils.
AB  - We developed a permeabilization method that retains coupling between N-formyl
      methionyl-leucyl-phenylalanine tripeptide (FMLP) receptor stimulation, shape
      changes, and barbed-end actin nucleation in human neutrophils. Using GTP
      analogues, phosphoinositides, a phosphoinositide-binding peptide, constitutively
      active or inactive Rho GTPase mutants, and activating or inhibitory peptides
      derived from neural Wiskott-Aldrich syndrome family proteins (N-WASP), we
      identified signaling pathways leading from the FMLP receptor to actin nucleation
      that require Cdc42, but then diverge. One branch traverses the actin nucleation
      pathway involving N-WASP and the Arp2/3 complex, whereas the other operates
      through active Rac to promote actin nucleation. Both pathways depend on
      phosphoinositide expression. Since maximal inhibition of the Arp2/3 pathway
      leaves an N17Rac inhibitable alternate pathway intact, we conclude that this
      alternate involves phosphoinositide-mediated uncapping of actin filament barbed
      ends.

PMID- 10953004
TI  - Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC
      phosphorylation for assembly of stress fibers and focal adhesions in 3T3
      fibroblasts.
AB  - ROCK (Rho-kinase), an effector molecule of RhoA, phosphorylates the myosin
      binding subunit (MBS) of myosin phosphatase and inhibits the phosphatase
      activity. This inhibition increases phosphorylation of myosin light chain (MLC)
      of myosin II, which is suggested to induce RhoA-mediated assembly of stress
      fibers and focal adhesions. ROCK is also known to directly phosphorylate MLC in
      vitro; however, the physiological significance of this MLC kinase activity is
      unknown. It is also not clear whether MLC phosphorylation alone is sufficient for
      the assembly of stress fibers and focal adhesions. We have developed two reagents
      with opposing effects on myosin phosphatase. One is an antibody against MBS that
      is able to inhibit myosin phosphatase activity. The other is a truncation mutant
      of MBS that constitutively activates myosin phosphatase. Through microinjection
      of these two reagents followed by immunofluorescence with a specific antibody
      against phosphorylated MLC, we have found that MLC phosphorylation is both
      necessary and sufficient for the assembly of stress fibers and focal adhesions in
      3T3 fibroblasts. The assembly of stress fibers in the center of cells requires
      ROCK activity in addition to the inhibition of myosin phosphatase, suggesting
      that ROCK not only inhibits myosin phosphatase but also phosphorylates MLC
      directly in the center of cells. At the cell periphery, on the other hand, MLCK
      but not ROCK appears to be the kinase responsible for phosphorylating MLC. These
      results suggest that ROCK and MLCK play distinct roles in spatial regulation of
      MLC phosphorylation.

PMID- 10953005
TI  - Stimulation of fascin spikes by thrombospondin-1 is mediated by the GTPases Rac
      and Cdc42.
AB  - Cell adhesion to extracellular matrix is an important physiological stimulus for
      organization of the actin-based cytoskeleton. Adhesion to the matrix glycoprotein
      thrombospondin-1 (TSP-1) triggers the sustained formation of F-actin microspikes
      that contain the actin-bundling protein fascin. These structures are also
      implicated in cell migration, which may be an important function of TSP-1 in
      tissue remodelling and wound repair. To further understand the function of fascin
      microspikes, we examined whether their assembly is regulated by Rho family
      GTPases. We report that expression of constitutively active mutants of Rac or
      Cdc42 triggered localization of fascin to lamellipodia, filopodia, and cell edges
      in fibroblasts or myoblasts. Biochemical assays demonstrated prolonged activation
      of Rac and Cdc42 in C2C12 cells adherent to TSP-1 and activation of the
      downstream kinase p21-activated kinase (PAK). Expression of dominant-negative Rac
      or Cdc42 in C2C12 myoblasts blocked spreading and formation of fascin spikes on
      TSP-1. Spreading and spike assembly were also blocked by pharmacological
      inhibition of F-actin turnover. Shear-loading of monospecific anti-fascin
      immunoglobulins, which block the binding of fascin to actin into cytoplasm,
      strongly inhibited spreading, actin cytoskeletal organization and migration on
      TSP-1 and also affected the motility of cells on fibronectin. We conclude that
      fascin is a critical component downstream of Rac and Cdc42 that is needed for
      actin cytoskeletal organization and cell migration responses to thrombospondin-1.

PMID- 10953006
TI  - Dynacortin, a genetic link between equatorial contractility and global shape
      control discovered by library complementation of a Dictyostelium discoideum
      cytokinesis mutant.
AB  - We have developed a system for performing interaction genetics in Dictyostelium
      discoideum that uses a cDNA library complementation/multicopy suppression
      strategy. Chemically mutagenized cells were screened for cytokinesis-deficient
      mutants and one mutant was subjected to library complementation. Isolates of four
      different genes were recovered as modifiers of this strain's cytokinesis defect.
      These include the cleavage furrow protein cortexillin I, a novel protein we named
      dynacortin, an ezrin-radixin-moesin-family protein, and coronin. The cortexillin
      I locus and transcript were found to be disrupted in the strain, identifying it
      as the affected gene. Dynacortin is localized partly to the cell cortex and
      becomes enriched in protrusive regions, a localization pattern that is similar to
      coronin and partly dependent on RacE. During cytokinesis, dynacortin is found in
      the cortex and is somewhat enriched at the poles. Furthermore, it appears to be
      reduced in the cleavage furrow. The genetic interactions and the cellular
      distributions of the proteins suggest a hypothesis for cytokinesis in which the
      contraction of the medial ring is a function of spatially restricted cortexillin
      I and myosin II and globally distributed dynacortin, coronin, and RacE.

PMID- 10953008
TI  - Polarized insertion of new membrane from a cytoplasmic reservoir during cleavage
      of the Drosophila embryo.
AB  - Cellularization of the Drosophila embryo is a specialized form of cytokinesis
      that results in the formation of a polarized epithelium. The mechanisms of
      membrane growth during cytokinesis are largely unknown. It is also unclear
      whether membrane growth and polarization represent distinct processes that occur
      simultaneously or whether growth of the membrane is involved in the emergence of
      polarity. Using a combination of surface labeling and particles tracking
      techniques, we monitored the dynamics of marked membrane regions during
      cellularization. We find that the major source of membrane is intracellular,
      rather than in the form of a plasma membrane reservoir. Depolymerization of
      microtubules inhibits the export of a newly synthesized transmembrane protein
      from the Golgi apparatus to the plasma membrane and simultaneously blocks
      membrane growth. Membrane insertion occurs in a defined sequence at specific
      sites, first apical, then apical-lateral. Diffusion of the membrane appears
      insufficient to compete with the massive local insertion of new membrane. We thus
      identify a tightly regulated scheme of polarized membrane insertion during
      cellularization. We propose that such a mechanism could participate in the
      progressive emergence of apical-basal polarity.

PMID- 10953007
TI  - Differential regulation of granule-to-granule and granule-to-plasma membrane
      fusion during secretion from rat pituitary lactotrophs.
AB  - We used fluorescence imaging of individual exocytic events together with electron
      microscopy to study the regulation of dense core granule-to-plasma membrane
      fusion and granule-to-granule fusion events that occur during secretion from rat
      pituitary lactotrophs. Stimulating secretion with elevated extracellular
      potassium, with the calcium ionophore ionomycin, or with thyrotropin releasing
      hormone or vasoactive intestinal polypeptide resulted in abundant exocytic
      structures. Approximately 67% of these structures consisted of multiple granules
      fused together sharing a single exocytic opening with the plasma membrane, i.e.,
      compound exocytosis. For all of these stimulation conditions there appeared to be
      a finite number of plasma membrane fusion sites, approximately 11 sites around
      each cellular equator. However, a granule could fuse directly with another
      granule that had already fused with the plasma membrane even before all plasma
      membrane sites were occupied. Granule-to-plasma membrane and granule-to-granule
      fusion events were subject to different regulations. Forskolin, which can elevate
      cAMP, increased the number of granule-to-granule fusion events without altering
      the number of granule-to-plasma membrane fusion events. In contrast, the phorbol
      ester PMA, which activates protein kinase C increased both granule-to-granule and
      granule-to-plasma membrane fusion events. These results provide a cellular
      mechanism that can account for the previously demonstrated potentiation of
      secretion from lactotrophs by cAMP- and PKC-dependent pathways.

PMID- 10953009
TI  - The roles of integrin-linked kinase in the regulation of myogenic
      differentiation.
AB  - Myogenic differentiation is a highly orchestrated, multistep process that is
      coordinately regulated by growth factors and cell adhesion. We show here that
      integrin-linked kinase (ILK), an intracellular integrin- and PINCH-binding
      serine/threonine protein kinase, is an important regulator of myogenic
      differentiation. ILK is abundantly expressed in C2C12 myoblasts, both before and
      after induction of terminal myogenic differentiation. However, a noticeable
      amount of ILK in the Triton X-100-soluble cellular fractions is significantly
      reduced during terminal myogenic differentiation, suggesting that ILK is involved
      in cellular control of myogenic differentiation. To further investigate this, we
      have overexpressed the wild-type and mutant forms of ILK in C2C12 myoblasts.
      Overexpression of ILK in the myoblasts inhibited the expression of myogenic
      proteins (myogenin, MyoD, and myosin heavy chain) and the subsequent formation of
      multinucleated myotubes. Furthermore, mutations that eliminate either the PINCH
      binding or the kinase activity of ILK abolished its ability to inhibit myogenic
      protein expression and allowed myotube formation. Although overexpression of the
      ILK mutants is permissive for the initiation of terminal myogenic
      differentiation, the myotubes derived from myoblasts overexpressing the ILK
      mutants frequently exhibited an abnormal morphology (giant myotubes containing
      clustered nuclei), suggesting that ILK functions not only in the initial decision
      making process, but also in later stages (fusion or maintaining myotube
      integrity) of myogenic differentiation. Additionally, we show that overexpression
      of ILK, but not that of the PINCH-binding defective or the kinase-deficient ILK
      mutants, prevents inactivation of MAP kinase, which is obligatory for the
      initiation of myogenic differentiation. Finally, inhibition of MAP kinase
      activation reversed the ILK-induced suppression of myogenic protein expression.
      Thus, ILK likely influences the initial decision making process of myogenic
      differentiation by regulation of MAP kinase activation.

PMID- 10953010
TI  - Cyclin E as a coactivator of the androgen receptor.
AB  - Androgens play an important role in the growth of prostate cancer, but the
      molecular mechanism that underlies development of resistance to antiandrogen
      therapy remains unknown. Cyclin E has now been shown to increase the
      transactivation activity of the human androgen receptor (AR) in the presence of
      its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was
      resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was
      shown to bind directly to the COOH terminus portion of the AB domain of the AR,
      and to enhance its AF-1 transactivation function. These results suggest that
      cyclin E functions as a coactivator of the AR, and that aberrant expression of
      cyclin E in tumors may contribute to persistent activation of AR function, even
      during androgen ablation therapy.

PMID- 10953011
TI  - Peroxisomal membrane fusion requires two AAA family ATPases, Pex1p and Pex6p.
AB  - Two AAA family ATPases, NSF and p97, have been implicated in membrane fusion
      during assembly and inheritance of organelles of the secretory pathway. We have
      now investigated the roles of AAA ATPases in membrane fusion during assembly of
      the peroxisome, an organelle outside the classical secretory system. Here, we
      show that peroxisomal membrane fusion in the yeast Yarrowia lipolytica requires
      two AAA ATPases, Pex1p and Pex6p. Release of membrane- associated Pex1p and Pex6p
      drives the asymmetric priming of two fusion partners. The next step, peroxisome
      docking, requires release of Pex1p from one partner. Subsequent fusion of the
      peroxisomal membranes is independent of both Pex1p and Pex6p.

PMID- 10953012
TI  - Cross-talk between two cysteine protease families. Activation of caspase-12 by
      calpain in apoptosis.
AB  - Calpains and caspases are two cysteine protease families that play important
      roles in regulating pathological cell death. Here, we report that m-calpain may
      be responsible for cleaving procaspase-12, a caspase localized in the ER, to
      generate active caspase-12. In addition, calpain may be responsible for cleaving
      the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into
      a proapoptotic molecule. We propose that disturbance to intracellular calcium
      storage as a result of ischemic injury or amyloid beta peptide cytotoxicity may
      induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL
      inactivation. These data suggest a novel apoptotic pathway involving calcium
      mediated calpain activation and cross-talks between calpain and caspase families.

PMID- 10953013
TI  - In vivo importance of actin nucleotide exchange catalyzed by profilin.
AB  - The actin monomer-binding protein, profilin, influences the dynamics of actin
      filaments in vitro by suppressing nucleation, enhancing nucleotide exchange on
      actin, and promoting barbed-end assembly. Profilin may also link signaling
      pathways to actin cytoskeleton organization by binding to the phosphoinositide
      PIP(2) and to polyproline stretches on several proteins. Although activities of
      profilin have been studied extensively in vitro, the significance of each of
      these activities in vivo needs to be tested. To study profilin function, we
      extensively mutagenized the Saccharomyces cerevisiae profilin gene (PFY1) and
      examined the consequences of specific point mutations on growth and actin
      organization. The actin-binding region of profilin was shown to be critical in
      vivo. act1-157, an actin mutant with an increased intrinsic rate of nucleotide
      exchange, suppressed defects in actin organization, cell growth, and fluid-phase
      endocytosis of pfy1-4, a profilin mutant defective in actin binding. In reactions
      containing actin, profilin, and cofilin, profilin was required for fast rates of
      actin filament turnover. However, Act1-157p circumvented the requirement for
      profilin. Based on the results of these studies, we conclude that in living cells
      profilin promotes rapid actin dynamics by regenerating ATP actin from ADP actin
      cofilin generated during filament disassembly.

PMID- 10953014
TI  - Tyrosine phosphorylation of Eps15 is required for ligand-regulated, but not
      constitutive, endocytosis.
AB  - Membrane receptors are internalized either constitutively or upon ligand
      engagement. Whereas there is evidence for differential regulation of the two
      processes, little is known about the molecular machinery involved. Previous
      studies have shown that an unidentified kinase substrate is required for
      endocytosis of the epidermal growth factor receptor (EGFR), the prototypical
      ligand-inducible receptor, but not of the transferrin receptor (TfR), the
      prototypical constitutively internalized receptor. Eps15, an endocytic protein
      that is tyrosine phosphorylated by EGFR, is a candidate for such a function.
      Here, we show that tyrosine phosphorylation of Eps15 is necessary for
      internalization of the EGFR, but not of the TfR. We mapped Tyr 850 as the major
      in vivo tyrosine phosphorylation site of Eps15. A phosphorylation-negative mutant
      of Eps15 acted as a dominant negative on the internalization of the EGFR, but not
      of the TfR. A phosphopeptide, corresponding to the phosphorylated sequence of
      Eps15, inhibited EGFR endocytosis, suggesting that phosphotyrosine in Eps15
      serves as a docking site for a phosphotyrosine binding protein. Thus, tyrosine
      phosphorylation of Eps15 represents the first molecular determinant, other than
      those contained in the receptors themselves, which is involved in the
      differential regulation of constitutive vs. regulated endocytosis.

PMID- 10953015
TI  - Tenascin-C suppresses Rho activation.
AB  - Cell binding to extracellular matrix (ECM) components changes cytoskeletal
      organization by the activation of Rho family GTPases. Tenascin-C, a
      developmentally regulated matrix protein, modulates cellular responses to other
      matrix proteins, such as fibronectin (FN). Here, we report that tenascin-C
      markedly altered cell phenotype on a three-dimensional fibrin matrix containing
      FN, resulting in suppression of actin stress fibers and induction of actin-rich
      filopodia. This distinct morphology was associated with complete suppression of
      the activation of RhoA, a small GTPase that induces actin stress fiber formation.
      Enforced activation of RhoA circumvented the effects of tenascin. Effects of
      active Rho were reversed by a Rho inhibitor C3 transferase. Suppression of GTPase
      activation allows tenascin-C expression to act as a regulatory switch to reverse
      the effects of adhesive proteins on Rho function. This represents a novel
      paradigm for the regulation of cytoskeletal organization by ECM.

PMID- 10953016
TI  - Introducing a null mutation in the mouse K6alpha and K6beta genes reveals their
      essential structural role in the oral mucosa.
AB  - Mammalian genomes feature multiple genes encoding highly related keratin 6 (K6)
      isoforms. These type II keratins show a complex regulation with constitutive and
      inducible components in several stratified epithelia, including the oral mucosa
      and skin. Two functional genes, K6alpha and K6beta, exist in a head-to-tail
      tandem array in mouse genomes. We inactivated these two genes simultaneously via
      targeting and homologous recombination. K6 null mice are viable and initially
      indistinguishable from their littermates. Starting at two to three days after
      birth, they show a growth delay associated with reduced milk intake and the
      presence of white plaques in the posterior region of dorsal tongue and upper
      palate. These regions are subjected to greater mechanical stress during suckling.
      Morphological analyses implicate the filiform papillae as being particularly
      sensitive to trauma in K6alpha/K6beta null mice, and establish the complete
      absence of keratin filaments in their anterior compartment. All null mice die
      about a week after birth. These studies demonstrate an essential structural role
      for K6 isoforms in the oral mucosa, and implicate filiform papillae as being the
      major stress bearing structures in dorsal tongue epithelium.

PMID- 10953017
TI  - Gap junctional communication in the early Xenopus embryo.
AB  - In the Xenopus embryo, blastomeres are joined by gap junctions that allow the
      movement of small molecules between neighboring cells. Previous studies using
      Lucifer yellow (LY) have reported asymmetries in the patterns of junctional
      communication suggesting involvement in dorso-ventral patterning. To explore that
      relationship, we systematically compared the transfer of LY and neurobiotin in
      embryos containing 16-128 cells. In all cases, the junction-permeable tracer was
      coinjected with a fluorescent dextran that cannot pass through gap junctions.
      Surprisingly, while LY appeared to transfer in whole-mount embryos, in no case
      did we observe junctional transfer of LY in fixed and sectioned embryos. The lack
      of correspondence between data obtained from whole-mounts and from sections
      results from two synergistic effects. First, uninjected blastomeres in whole
      mounts reflect and scatter light originating from the intensely fluorescent
      injected cell, creating a diffuse background interpretable as dye transfer.
      Second, the heavier pigmentation in ventral blastomeres masks this scattered
      signal, giving the impression of an asymmetry in communication. Thus, inspection
      of whole-mount embryos is an unreliable method for the assessment of dye transfer
      between embryonic blastomeres. A rigorous and unambiguous demonstration of gap
      junctional intercellular communication demands both the coinjection of permeant
      and impermeant tracers followed by the examination of sectioned specimens.
      Whereas LY transfer was never observed, neurobiotin was consistently transferred
      in both ventral and dorsal aspects of the embryo, with no apparent asymmetry.
      Ventralization of embryos by UV irradiation and dorsalization by Xwnt-8 did not
      alter the patterns of communication. Thus, our results are not compatible with
      current models for a role of gap junctional communication in dorso-ventral
      patterning.

PMID- 10953018
TI  - Rho GTPases. Integrating integrin signaling.

PMID- 10953019
TI  - Insulin resistance and cardiovascular disease.

PMID- 10953020
TI  - Insights into insulin resistance and type 2 diabetes from knockout mouse models.

PMID- 10953021
TI  - Treatment of insulin resistance with peroxisome proliferator-activated receptor
      gamma agonists.

PMID- 10953022
TI  - Obesity and insulin resistance.

PMID- 10953023
TI  - Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia.
AB  - Homocysteine is a risk factor for the development of atherosclerosis and its
      thrombotic complications. We have employed an animal model to explore the
      hypothesis that an increase in reactive oxygen species and a subsequent loss of
      nitric oxide bioactivity contribute to endothelial dysfunction in mild
      hyperhomocysteinemia. We examined endothelial function and in vivo oxidant burden
      in mice heterozygous for a deletion in the cystathionine beta-synthase (CBS)
      gene, by studying isolated, precontracted aortic rings and mesenteric arterioles
      in situ. CBS(-/+) mice demonstrated impaired acetylcholine-induced aortic
      relaxation and a paradoxical vasoconstriction of mesenteric microvessels in
      response to superfusion of methacholine and bradykinin. Cyclic GMP accumulation
      following acetylcholine treatment was also impaired in isolated aortic segments
      from CBS(-/+) mice, but aortic relaxation and mesenteric arteriolar dilation in
      response to sodium nitroprusside were similar to wild-type. Plasma levels of 8
      epi-PGF(2alpha) (8-IP) were somewhat increased in CBS(-/+) mice, but liver levels
      of 8-IP and phospholipid hydroperoxides, another marker of oxidative stress, were
      normal. Aortic tissue from CBS(-/+) mice also demonstrated greater superoxide
      production and greater immunostaining for 3-nitrotyrosine, particularly on the
      endothelial surface. Importantly, endothelial dysfunction appears early in CBS(
      /+) mice in the absence of structural arterial abnormalities. Hence, mild
      hyperhomocysteinemia due to reduced CBS expression impairs endothelium-dependent
      vasodilation, likely due to impaired nitric oxide bioactivity, and increased
      oxidative stress apparently contributes to inactivating nitric oxide in chronic,
      mild hyperhomocysteinemia.

PMID- 10953024
TI  - Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent
      vasomotor activity in vivo.
AB  - The serine/threonine protein kinase Akt (protein kinase B) phosphorylates
      endothelial cell nitric oxide synthase (eNOS) and enhances its ability to
      generate nitric oxide (NO). Because NO is an important regulator of vasomotor
      tone, we investigated whether Akt can regulate endothelium-dependent vasomotion
      in vivo using a rabbit femoral artery model of gene transfer. The endothelium of
      isolated femoral arteries was infected with replication-defective adenoviral
      constructs expressing beta-galactosidase, constitutively-active Akt (myr-Akt), or
      dominant-negative Akt (dn-Akt). Femoral arteries transduced with myr-Akt showed a
      significant increase in resting diameter and blood flow, as assessed by
      angiography and Doppler flow measurements, respectively. L-NAME, an eNOS
      inhibitor, blocked myr-Akt-mediated vasodilatation. In contrast, endothelium
      dependent vasodilatation in response to acetylcholine was attenuated in vessels
      transduced with dn-Akt, although these vessels showed normal responses to
      nitroglycerin, an endothelium-independent vasodilator. Similarly, relaxation of
      murine aorta ex vivo in response to acetylcholine, but not nitroglycerin, was
      inhibited by transduction of dn-Akt to the endothelium. These data provide
      evidence that Akt functions as key regulator of vasomotor tone in vivo.

PMID- 10953025
TI  - Leptin enhances wound re-epithelialization and constitutes a direct function of
      leptin in skin repair.
AB  - Wound-healing disorders are a therapeutic problem of extensive clinical
      importance. Leptin-deficient ob/ob mice are characterized by a severely delayed
      wound healing that has been explained by the mild diabetic phenotype of these
      animals. Here we demonstrate that systemically and topically supplemented leptin
      improved re-epithelialization of wounds in ob/ob mice. Leptin completely reversed
      the atrophied morphology of the migrating epithelial tongue observed at the wound
      margins of leptin-deficient animals into a well-organized hyperproliferative
      epithelium. Moreover, topically supplemented leptin accelerated normal wound
      healing conditions in wild-type mice. As assessed by immunohistochemistry,
      proliferating keratinocytes located at the wound margins specifically expressed
      the leptin-receptor subtype ObRb during repair. Additionally, leptin mediated a
      mitogenic stimulus to the human keratinocyte cell line HaCaT and human primary
      keratinocytes in vitro. Therefore, leptin might represent an effective novel
      therapeutic factor to improve impaired wound-healing conditions.

PMID- 10953026
TI  - Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and
      migration.
AB  - Emerging data suggest that VEGF receptors are expressed by endothelial cells as
      well as hematopoietic stem cells. Therefore, we hypothesized that functional VEGF
      receptors may also be expressed in malignant counterparts of hematopoietic stem
      cells such as leukemias. We demonstrate that certain leukemias not only produce
      VEGF but also express functional VEGFR-2 in vivo and in vitro, resulting in the
      generation of an autocrine loop that may support leukemic cell survival and
      proliferation. Approximately 50% of freshly isolated leukemias expressed mRNA and
      protein for VEGFR-2. VEGF(165) induced phosphorylation of VEGFR-2 and increased
      proliferation of leukemic cells, demonstrating these receptors were functional.
      VEGF(165) also induced the expression of MMP-9 by leukemic cells and promoted
      their migration through reconstituted basement membrane. The neutralizing mAb IMC
      1C11, specific to human VEGFR-2, inhibited leukemic cell survival in vitro and
      blocked VEGF(165)-mediated proliferation of leukemic cells and VEGF-induced
      leukemic cell migration. Xenotransplantation of primary leukemias and leukemic
      cell lines into immunocompromised nonobese diabetic mice resulted in significant
      elevation of human, but not murine, VEGF in plasma and death of inoculated mice
      within 3 weeks. Injection of IMC-1C11 inhibited proliferation of xenotransplanted
      human leukemias and significantly increased the survival of inoculated mice.
      Interruption of signaling by VEGFRs, particularly VEGFR-2, may provide a novel
      strategy for inhibiting leukemic cell proliferation.

PMID- 10953027
TI  - Peroxisome proliferator-activated receptor gamma ligands inhibit development of
      atherosclerosis in LDL receptor-deficient mice.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that regulates fat-cell development and glucose homeostasis and is the
      molecular target of a class of insulin-sensitizing agents used for the management
      of type 2 diabetes mellitus. PPARgamma is highly expressed in macrophage foam
      cells of atherosclerotic lesions and has been demonstrated in cultured
      macrophages to both positively and negatively regulate genes implicated in the
      development of atherosclerosis. We report here that the PPARgamma-specific
      agonists rosiglitazone and GW7845 strongly inhibited the development of
      atherosclerosis in LDL receptor-deficient male mice, despite increased expression
      of the CD36 scavenger receptor in the arterial wall. The antiatherogenic effect
      in male mice was correlated with improved insulin sensitivity and decreased
      tissue expression of TNF-alpha and gelatinase B, indicating both systemic and
      local actions of PPARgamma. These findings suggest that PPARgamma agonists may
      exert antiatherogenic effects in diabetic patients and provide impetus for
      efforts to develop PPARgamma ligands that separate proatherogenic activities from
      antidiabetic and antiatherogenic activities.

PMID- 10953028
TI  - Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model
      of intestinal polyposis.
AB  - Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene occur in
      most colorectal cancers and lead to activation of beta-catenin. Whereas several
      downstream targets of beta-catenin have been identified (c-myc, cyclin D1,
      PPARdelta), the precise functional significance of many of these targets has not
      been examined directly using genetic approaches. Previous studies have shown that
      the gene encoding the hormone gastrin is activated during colon cancer
      progression and the less-processed forms of gastrin are important colonic trophic
      factors. We show here that the gastrin gene is a downstream target of the beta
      catenin/TCF-4 signaling pathway and that cotransfection of a constitutively
      active beta-catenin expression construct causes a threefold increase in gastrin
      promoter activity. APC(min-/+) mice overexpressing one of the alternatively
      processed forms of gastrin, glycine-extended gastrin, show a significant increase
      in polyp number. Gastrin-deficient APC(min-/+) mice, conversely, showed a marked
      decrease in polyp number and a significantly decreased polyp proliferation rate.
      Activation of gastrin by beta-catenin may therefore represent an early event in
      colorectal tumorigenesis and may contribute significantly toward neoplastic
      progression. The identification of gastrin as a functionally relevant downstream
      target of the beta-catenin signaling pathway provides a new target for
      therapeutic modalities in the treatment of colorectal cancer.

PMID- 10953029
TI  - Retinal expression, regulation, and functional bioactivity of prostacyclin
      stimulating factor.
AB  - Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to
      stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have
      examined the expression, regulation, and hemodynamic bioactivity of PSF both in
      whole retina and in cultured cells derived from this tissue. PSF was expressed in
      all retinal cell types examined in vitro, but immunohistochemical analysis
      revealed PSF mainly associated with retinal vessels. PSF expression was
      constitutive in retinal pericytes (RPCs) but could be modulated in bovine retinal
      capillary endothelial cells (RECs) by cell confluency, hypoxia, serum starvation,
      high glucose concentrations, or inversely by soluble factors present in early vs.
      late retinopathy, such as TGF-beta, VEGF, or bFGF. In addition, RPC-conditioned
      media dramatically increased REC PGI2 production, a response inhibited by
      blocking PSF with a specific antisense oligodeoxynucleotide (ODN). In vivo, PGI2
      increased retinal blood flow (RBF) in control and diabetic animals. Furthermore,
      the early drop in RBF during the initial weeks after inducing diabetes in rats,
      as well as the later increase in RBF, both correlated with levels of retinal PSF.
      RBF also responded to treatment with RPC-conditioned media, and this effect could
      be partially blocked using the antisense PSF ODN. We conclude that PSF expressed
      by ocular cells can induce PGI2, retinal vascular dilation, and increased retinal
      blood flow, and that alterations in retinal PSF expression may explain the
      biphasic changes in RBF observed in diabetes.

PMID- 10953030
TI  - Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to
      eosinophilic airway inflammation.
AB  - The aim of this study was to investigate whether dendritic cells (DCs) can induce
      sensitization to aeroallergen in a mouse model of allergic asthma. Ovalbumin
      pulsed (OVA-pulsed) or unpulsed myeloid DCs that were injected into the airways
      of naive mice migrated into the mediastinal lymph nodes. When challenged 2 weeks
      later with an aerosol of OVA, activated CD4 and CD8 lymphocytes, eosinophils, and
      neutrophils were recruited to the lungs of actively immunized mice. These CD4(+)
      lymphocytes produced predominantly IL-4 and IL-5 but also IFN-gamma, whereas
      CD8(+) lymphocytes produced predominantly IFN-gamma. Histological analysis
      revealed perivascular and peribronchial eosinophilic infiltrates and goblet cell
      hyperplasia. Studies in IL-4(-/-) and CD28(-/-) mice revealed that production of
      IL-4 by host cells and provision of costimulation to T cells by DCs were critical
      for inducing the response. Lung CD4(+) T cells strongly expressed the Th2 marker
      T1/ST2, and signaling through this molecule via a ligand expressed on DCs was
      essential for the establishment of airway eosinophilia. These data demonstrate
      that DCs in the airways induce sensitization to inhaled antigen and that
      molecules expressed on the surface of these cells are critical for the
      development of Th2-dependent airway eosinophilia.

PMID- 10953031
TI  - Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer
      surface protein A.
AB  - Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme
      disease vaccine that blocks transmission: OspA antibodies of immune hosts enter
      ticks during blood feeding and destroy spirochetes before transmission to the
      host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis
      ticks, and many spirochetes repress OspA production during the feeding process.
      This preferential expression suggests that OspA may have an important function in
      the vector. Here we show that OspA mediates spirochete attachment to the tick gut
      by binding to an I. scapularis protein. The binding domains reside in the central
      region and COOH-terminus of OspA. OspA also binds to itself, suggesting that
      spirochete-spirochete interactions may further facilitate adherence in the gut.
      OspA-mediated attachment in the tick provides a possible mechanism for how stage
      specific protein expression can contribute to pathogenesis during the B.
      burgdorferi natural cycle.

PMID- 10953032
TI  - Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice.
AB  - Endothelial cell progenitors, angioblasts, have been detected in the peripheral
      blood of adult humans, mice, and rabbits. These cells have been shown to
      incorporate into the endothelium of newly forming blood vessels in pathological
      and nonpathological conditions. Here we investigated the possibility that the
      CD34-expressing leukocytes (CD34(+) cells) that appear to be enriched for
      angioblasts could be used to accelerate the rate of blood-flow restoration in
      nondiabetic and diabetic mice undergoing neovascularization due to hindlimb
      ischemia. CD34(+) cells did not accelerate the restoration of flow in nondiabetic
      mice, but dramatically increased it in diabetic mice. Furthermore, CD34(+) cells
      derived from type 1 diabetics produced fewer differentiated endothelial cells in
      culture than did their type 2 diabetic- or nondiabetic-derived counterparts. In
      vitro experiments suggest that hyperglycemia per se does not alter the ability of
      angioblasts to differentiate or of angioblast-derived endothelial cells to
      proliferate. In contrast, hyperinsulinemia may enhance angioblast differentiation
      but impair angioblast-derived endothelial cell survival or proliferation. Our
      findings suggest that CD34(+) cells may be a useful tool for therapeutic
      angiogenesis in diabetics.

PMID- 10953033
TI  - Thrombin activates a Y box-binding protein (DNA-binding protein B) in endothelial
      cells.
AB  - Thrombin stimulates the expression of multiple genes in endothelial cells (ECs),
      but the trans-acting factors responsible for this induction remain undefined. We
      have previously described a thrombin-inducible nuclear factor (TINF), which binds
      to an element in the PDGF B promoter and is responsible for the thrombin
      inducibility of this gene. Inactive cytoplasmic TINF is rapidly activated and
      translocated to nuclei of ECs upon stimulation with thrombin. We have now
      purified TINF from thrombin-treated ECs. Amino acid sequencing revealed it to be
      a member of the Y-box protein family, and the sole Y-box protein-encoding cDNA we
      detected in human or bovine ECs corresponded to DNA-binding protein B (dbpB).
      DbpB translocated to the nucleus after thrombin stimulation of ECs as shown by
      FACS analysis of nuclei from ECs expressing GFP-dbpB fusion proteins. During
      thrombin activation, dbpB was found to be cleaved, yielding a 30-kDa NH(2)
      terminal fragment that recognized the thrombin-response element sequence, but not
      the Y-box consensus sequence. Preincubation of ECs with protein tyrosine
      phosphatase inhibitors completely blocked dbpB activation by thrombin and blocked
      induction of endogenous PDGF B-chain mRNA and promoter activation by thrombin. Y
      box proteins are known to act constitutively to regulate the expression of
      several genes. Activation of this class of transcription factors in response to
      thrombin or any other agonist represents a novel signaling pathway.

PMID- 10953036
TI  - A novel signaling mechanism between gas and blood compartments of the lung

PMID- 10953034
TI  - Sex-related survival differences in murine cardiomyopathy are associated with
      differences in TNF-receptor expression.
AB  - Epidemiological evidence suggests that the prognosis of heart failure in women is
      better than in men. In our murine model of dilated cardiomyopathy arising from
      cardiac-specific overexpression of TNF-alpha, the 6-month survival rate was
      significantly better in females than in males. Young female transgenic mice
      exhibited left ventricular wall thickening without dilatation, whereas age
      matched male transgenic hearts were markedly dilated. Basal and isoproterenol
      stimulated fractional shortening was preserved in female transgenic mice, but not
      in male transgenic mice. Myocardial expression of proinflammatory cytokines and
      the extent of myocardial infiltrates were similar in male and female transgenic
      mice. Myocardial expression of TNF-receptor mRNAs (type I and type II) was
      significantly higher in male mice in both transgenic and wild-type littermates,
      whereas sex-specific differences were not observed in either peripheral white
      blood cells or liver tissue. After TNF-alpha challenge, myocardial but not liver
      production of ceramide was significantly higher in male than in female mice.
      Thus, differential expression of myocardial TNF receptors may contribute to sex
      differences in the severity of congestive heart failure and mortality consequent
      to cardiac-specific overexpression of TNF-alpha.

PMID- 10953037
TI  - Pentobarbital modulates gamma-aminobutyric acid-activated single-channel
      conductance in rat cultured hippocampal neurons.
AB  - We examined the effect of a range of pentobarbital concentrations on 0.5 microM
      gamma-aminobutyric acid (GABA)-activated channels (10 +/- 1 pS) in inside-out or
      outside-out patches from rat cultured hippocampal neurons. The conductance
      increased from 12 +/- 4 to 62 +/- 9 pS as the pentobarbital concentration was
      raised from 10 to 500 microM and the data could be fitted by a Hill-type
      equation. At 100 microM pentobarbital plus 0.5 microM GABA, the conductance
      seemed to reach a plateau. The pentobarbital EC(50)(0.5 microM GABA) value was 22
      +/- 4 microM and n was 1.9 +/- 0.5. In 1 mM pentobarbital plus 0.5 microM GABA,
      the single-channel conductance decreased to 34 +/- 8 pS. This apparent inhibition
      of channel conductance was relieved by 1 microM diazepam. The channel conductance
      was 64 +/- 6 pS in the presence of all three drugs. The channels were open more
      in the presence of both GABA and pentobarbital than in the presence of either
      drug alone. Pentobarbital alone (100 microM) activated channels with conductance
      (30 +/- 2 pS) and kinetic properties distinct from those activated by either GABA
      alone or GABA plus pentobarbital. Whether pentobarbital induces new conformations
      or promotes conformations observed in the presence of GABA alone cannot be
      determined from our study, but the results clearly show that it is the
      combination of drugs present that determines the single-channel conductance and
      the kinetic properties of the receptors.

PMID- 10953035
TI  - Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH
      II gene.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the
      de novo synthesis of guanine nucleotides, which are also synthesized from guanine
      by a salvage reaction catalyzed by the X chromosome-linked enzyme hypoxanthine
      guanine phosphoribosyltransferase (HPRT). Since inhibitors of IMPDH are in
      clinical use as immunosuppressive agents, we have examined the consequences of
      knocking out the IMPDH type II enzyme by gene targeting in a mouse model. Loss of
      both alleles of the gene encoding this enzyme results in very early embryonic
      lethality despite the presence of IMPDH type I and HPRT activities. Lymphocytes
      from IMPDH II(+/-) heterozygous mice are normal with respect to subpopulation
      distribution and respond normally to a variety of mitogenic stimuli. However,
      mice with an IMPDH II(+/-), HPRT(-/o) genotype demonstrate significantly
      decreased lymphocyte responsiveness to stimulation with anti-CD3 and anti-CD28
      antibodies and show a 30% mean reduction in GTP levels in lymphocytes activated
      by these antibodies. Furthermore, the cytolytic activity of their T cells against
      allogeneic target cells is significantly impaired. These results demonstrate that
      a moderate decrease in the ability of murine lymphocytes to synthesize guanine
      nucleotides during stimulation results in significant impairment in T-cell
      activation and function.

PMID- 10953038
TI  - Evidence for peroxisome proliferator-activated receptor (PPAR)alpha-independent
      peroxisome proliferation: effects of PPARgamma/delta-specific agonists in
      PPARalpha-null mice.
AB  - Peroxisome proliferators are a diverse group of compounds that cause hepatic
      hypertrophy and hyperplasia, increase peroxisome number, and on chronic high-dose
      administration, lead to rodent liver tumorigenesis. Various lines of evidence
      have led to the conclusion that these agents induce their pleiotropic effects
      exclusively via agonism of peroxisome proliferator-activated receptor
      (PPAR)alpha, a member of the steroid receptor superfamily involved in the
      regulation of fatty acid metabolism. Recently, agonists of two other members of
      this receptor family have been identified. PPARgamma is predominantly expressed
      in adipocytes where it mediates differentiation; PPARdelta is a widely expressed
      orphan receptor with yet unresolved physiologic functions. In the course of
      characterizing newer PPAR ligands, we noted that highly selective PPARgamma
      agonists or dual PPARgamma/PPARdelta agonists, lacking apparent murine PPARalpha
      agonist activity, cause peroxisome proliferation in CD-1 mice. We therefore made
      use of PPARalpha knockout mice to investigate whether these effects resulted from
      agonism of PPARalpha by these agents at very high dose levels or whether
      PPARgamma (or PPARdelta) agonism alone can result in peroxisome proliferation. We
      report here that several parameters linked to the hepatic peroxisome
      proliferation response in mice that were seen with these agents resulted from
      PPARalpha-independent effects.

PMID- 10953039
TI  - Human adenosine A(1), A(2A), A(2B), and A(3) receptors expressed in Chinese
      hamster ovary cells all mediate the phosphorylation of extracellular-regulated
      kinase 1/2.
AB  - The known diverse effects of adenosine on mitogenesis may be related to changes
      in mitogen-activated protein kinases. In this study we therefore compared the
      phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) via the four known
      human adenosine receptors A(1), A(2A), A(2B), and A(3), stably transfected into
      Chinese hamster ovary (CHO) cells. The adenosine analog 5'-N
      ethylcarboxamidoadenosine (NECA), known to act on all subtypes, had no effect on
      untransfected CHO cells, but did cause a substantial time- and dose-dependent
      phosphorylation in CHO cells transfected with each of the receptors. The maximal
      phosphorylation was highest in A(1) and A(3) receptor-transfected cells,
      intermediate in A(2A) and low in A(2B) receptor-expressing CHO cells. For all
      receptors the half-maximal ERK1/2 phosphorylation was observed at 19-115 nM NECA.
      NECA acting on adenosine A(2B) receptors was much more potent in stimulating
      ERK1/2 phosphorylation (EC(50) = 19 nM) than cAMP formation (EC(50) = 1.4
      microM). Stimulation with the endogenous ligand adenosine resulted in the same
      pattern of ERK1/2 phosphorylation as NECA. Concentrations of adenosine that occur
      physiologically caused an increased phosphorylation after 5 min in CHO cells
      transfected with any one of the four adenosine receptors. Adenosine at levels
      reached during ischemia (3 microM) induced a more pronounced, but still
      transient, activation of ERK1/2. In conclusion, this study shows that all the
      human adenosine receptors transfected into CHO cells are able to activate ERK1/2
      at physiologically relevant concentrations of the endogenous agonist.

PMID- 10953040
TI  - Induction of the cytochrome P450 gene CYP26 during mucous cell differentiation of
      normal human tracheobronchial epithelial cells.
AB  - In this study, the expression of CYP26 is examined in relation to retinoid
      induced mucosecretory differentiation in human tracheobronchial epithelial (HTBE)
      cells and compared with that in human lung carcinoma cell lines. In HTBE cells,
      retinoic acid (RA) inhibits squamous differentiation and induces mucous cell
      differentiation as indicated by the suppression of transglutaminase I and
      increased expression of the mucin gene MUC2. The latter is accompanied by
      increased expression of CYP26 mRNA. RA is required but not sufficient to induce
      RARbeta, CYP26, and MUC2 mRNA because induction is only observed in confluent but
      not in logarithmic cultures, suggesting that additional factors are critical in
      their regulation. CYP26 mRNA can be induced by the RAR-selective retinoid 4
      (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)-benzoic acid (TTAB) but
      not by the RXR-selective retinoid SR11217 or the anti-activator-protein 1
      selective retinoid SR11302. RARalpha-, beta-, and gamma-selective retinoids are
      able to induce CYP26; this induction is inhibited by the RARalpha-selective
      antagonist Ro41-5253. TTAB is able to induce CYP26 mRNA expression in only a few
      of the lung carcinoma cell lines tested. The lack of CYP26 induction in many
      carcinoma cell lines may relate to previously reported defects in the retinoid
      signaling pathway. The induction of CYP26 correlated with increased metabolism of
      RA into 18-hydroxy-, 4-oxo-, and 4-hydroxy-RA. The latter metabolite was shown to
      be able to induce MUC2 and MUC5AC expression in HTBE cells. Our results
      demonstrate that in normal HTBE cells, CYP26 expression is closely associated
      with mucous cell differentiation and that many lung carcinoma cells exhibit
      increased RA metabolism and a defective regulation of CYP26.

PMID- 10953041
TI  - Stimulation of sphingosine-1-phosphate formation by the P2Y(2) receptor in HL-60
      cells: Ca(2+) requirement and implication in receptor-mediated Ca(2+)
      mobilization, but not MAP kinase activation.
AB  - Sphingosine-1-phosphate (SPP), produced by sphingosine kinase, has recently been
      reported to act as an intracellular second messenger for Ca(2+) and mitogenic
      responses triggered by membrane receptors and as an extracellular ligand for
      specific SPP receptors. Here, we investigated the signaling pathway leading to
      SPP production by the G protein-coupled P2Y(2) receptor and its functional
      implication in human leukemia (HL-60) cells, which do not respond to
      extracellular SPP. P2Y(2) receptor activation by UTP or ATP resulted in rapid and
      transient production of SPP, which was insensitive to pertussis toxin and blocked
      by the sphingosine kinase inhibitor, DL-threo-dihydrosphingosine. Treatment of HL
      60 cells with this inhibitor did not affect activation of mitogen-activated
      protein kinases, but suppressed Ca(2+) mobilization by the P2Y(2) receptor.
      However, receptor-induced SPP production apparently required an increase in
      intracellular Ca(2+) concentration, but not Ca(2+) influx, and was mimicked by
      exposure of cells to Ca(2+) ionophores. Taken together, activation of the P2Y(2)
      receptor stimulates SPP production in HL-60 cells, a process apparently not
      required for mitogen-activated protein kinase activation, but most likely
      representing an amplification system for receptor-mediated Ca(2+) signaling.

PMID- 10953042
TI  - Pharmacological characterization of chloride channels belonging to the ClC family
      by the use of chiral clofibric acid derivatives.
AB  - The enantiomers of 2-(p-chlorophenoxy)propionic acid (CPP) and of its analogs
      with substitutions on the asymmetric carbon atom were tested on human ClC-1
      channel, the skeletal muscle chloride channel, after heterologous expression in
      Xenopus laevis oocytes, to gain insight in the mechanism of action of these
      stereoselective modulators of macroscopic chloride conductance (gCl) of rat
      striated fibers. By means of two microelectrode voltage clamp recordings, we
      found that S(-)-CPP shifted the activation curve of the ClC-1 currents toward
      more positive potentials and decreased the residual conductance at negative
      membrane potential; both effects probably account for the decrease of gCl at
      resting potential of native muscle fibers. Experiments on expressed Torpedo
      marmorata ClC-0 channels and a mutant lacking the slow gate suggest that S(-)-CPP
      could act on the fast gate of the single protochannels constituting the double
      barreled structure of ClC-0 and ClC-1. The effect of S(-)-CPP on ClC-1 was
      markedly increased at low external pH (pH = 6), possibly for enhanced diffusion
      through the membrane (i.e., because the compound was effective only when applied
      to the cytoplasmic side during patch clamp recordings). The R(+)-isomer had
      little effect at concentrations as high as 1 mM. The CPP analogs with an ethyl, a
      phenyl, or an n-propyl group in place of the methyl group on the asymmetric
      center showed a scale of potency and a stereoselective behavior on ClC-1 similar
      to that observed for blocking gCl in native muscle fibers. The tested compounds
      were selective toward the ClC-1 channel. In fact, they were almost ineffective on
      an N-terminal deletion mutant of ClC-2 that is volume- and pH-independent while
      they blocked wild-type ClC-2 currents only at high concentrations and
      independently of pH and drug configuration, suggesting a different mechanism of
      action compared with ClC-1. No effects were observed on ClC-5 that shows less
      than 30% homology with ClC-1. Thus, CPP-like compounds may be useful both to gain
      insight into biophysical properties of ClC-1 and for searching tissue-specific
      therapeutic agents.

PMID- 10953043
TI  - Dual mechanisms of action of the retinoid CD437: nuclear retinoic acid receptor
      mediated suppression of squamous differentiation and receptor-independent
      induction of apoptosis in UMSCC22B human head and neck squamous cell carcinoma
      cells.
AB  - The synthetic retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic
      acid (CD437), which can bind to and activate the nuclear retinoic acid receptors
      beta and gamma (RARbeta/gamma), is a potent inducer of apoptosis in various
      cancer cell lines. However, this effect was reported to be independent of RARs.
      In this study, we compared and contrasted the potencies and mechanisms of action
      of CD437 and several other receptor-selective retinoids in induction of apoptosis
      and modulation of squamous differentiation in UMSCC22B human head and neck
      squamous cell carcinoma cell line. CD437 and the structurally related retinoid
      CD2325 exhibited almost equal potency in inducing apoptosis, whereas several
      other retinoids failed to induce apoptosis. The RAR-specific pan antagonist
      AGN193109 failed to suppress CD437-induced apoptosis, indicating that the
      induction of apoptosis by CD437 was RAR-independent. c-Fos expression was induced
      by CD437 and CD2325 that induced apoptosis in the cell line but not by other
      retinoids that failed to induce apoptosis, suggesting a role for c-Fos in CD437
      induced apoptosis. At low concentration (0.01 microM), CD437 shared with several
      other receptor-selective retinoids the ability to suppress the mRNA levels of the
      squamous differentiation markers Spr1, involucrin, and cytokeratin 1. This effect
      of CD437 could be blocked by AGN193109. We conclude that CD437 can exert its
      effects in UMSCC22B human human head and neck squamous cell carcinoma cells by at
      least two mechanisms: RAR-mediated suppression of squamous differentiation and
      RAR-independent induction of apoptosis.

PMID- 10953044
TI  - The bioflavonoid galangin blocks aryl hydrocarbon receptor activation and
      polycyclic aromatic hydrocarbon-induced pre-B cell apoptosis.
AB  - Bioflavonoids are plant compounds touted for their potential to treat or prevent
      several diseases including cancers induced by common environmental chemicals.
      Much of the biologic activity of one such class of pollutants, polycyclic
      aromatic hydrocarbons (PAH), is mediated by the aryl hydrocarbon
      receptor/transcription factor (AhR). For example, the AhR regulates PAH
      immunotoxicity that manifests as pre-B cell apoptosis in models of B cell
      development. Because bioflavonoids block PAH-induced cell transformation and are
      structurally similar to AhR ligands, it was postulated that some of them would
      suppress PAH-induced, AhR-dependent immunotoxicity, possibly through a direct AhR
      blockade. This hypothesis was tested using a model of B cell development in which
      pre-B cells are cultured with and are dependent on bone marrow stromal or hepatic
      parenchymal cell monolayers. Of seven bioflavonoids screened, galangin (3,5,7
      trihydroxyflavone) blocked PAH-induced but not C(2)-ceramide- or H(2)O(2)-induced
      pre-B cell apoptosis. Because galangin blocked AhR-dependent reporter gene
      expression, AhR complex-DNA binding, and AhR nuclear translocation, inhibition of
      a relatively early step in AhR signaling was implicated. This hypothesis was
      supported by the ability of galangin to bind the AhR and stabilize AhR-90-kDa
      heat shock protein complexes in the presence of AhR agonists. These studies
      demonstrate the utility of pre-B cell culture systems in identifying compounds
      capable of blocking PAH immunotoxicity, define at least one mechanism of galangin
      activity (i.e., repression of AhR activation), and motivate the use of this and
      similar dietary bioflavonoids as relatively nontoxic inhibitors of AhR agonist
      activity and as pharmacologic agents with which to dissect AhR signaling
      pathways.

PMID- 10953045
TI  - 2'-hydroxychalcone inhibits nuclear factor-kappaB and blocks tumor necrosis
      factor-alpha- and lipopolysaccharide-induced adhesion of neutrophils to human
      umbilical vein endothelial cells.
AB  - Inhibition of expression of cell adhesion molecules (CAM), including
      intercellular CAM-1 (ICAM-1), vascular CAM-1 (VCAM-1), and E-selectin, has been
      shown to be important in controlling various inflammatory diseases. The cell
      adhesion proteins are induced by various inflammatory cytokines, such as tumor
      necrosis factor-alpha, interleukin-1, and bacterial lipopolysaccharide. The
      induction process primarily takes place at the level of transcription, where
      nuclear factor-kappaB (NF-kappaB) plays a major role. We demonstrate here that 2'
      hydroxychalcone inhibits the adhesion of peripheral neutrophils to the
      endothelial cell monolayers by inhibiting the expression of ICAM-1, VCAM-1, and E
      selectin in a concentration-dependent manner. The inhibition by 2'
      hydroxychalcone is reversible. 2'-hydroxychalcone inhibits the induction of
      steady-state transcript levels of ICAM-1, VCAM-1, and E-selectin by tumor
      necrosis factor-alpha as determined by reverse transcription-polymerase chain
      reaction, and therefore it may interfere with the transcription of their genes.
      Because NF-kappaB is a major transcription factor involved in CAM expression, we
      studied its status in the 2'-hydroxychalcone treated cells. We demonstrate that
      2'-hydroxychalcone inhibits the activation of NF-kappaB. These results have
      implications for using NF-kappaB inhibitors for the treatment of various
      inflammatory diseases.

PMID- 10953047
TI  - Human microsomal epoxide hydrolase is the target of germander-induced
      autoantibodies on the surface of human hepatocytes.
AB  - Germander, a plant used in folk medicine, caused an epidemic of cytolytic
      hepatitis in France. In about half of these patients, a rechallenge caused early
      recurrence, suggesting an immunoallergic type of hepatitis. Teucrin A (TA) was
      found responsible for the hepatotoxicity via metabolic activation by CYP3A. In
      this study, we describe the presence of anti-microsomal epoxide hydrolase (EH)
      autoantibodies in the sera of patients who drank germander teas for a long period
      of time. By Western blotting and immunocytochemistry, human microsomal EH was
      shown to be present in purified plasma membranes of both human hepatocytes and
      transformed spheroplasts and to be exposed on the cell surface where affinity
      purified germander autoantibodies recognized it as their autoantigen.
      Immunoprecipitation of EH activity by germander-induced autoantibodies confirmed
      this finding. These autoantibodies were not immunoinhibitory. The plasma membrane
      located EH was catalytically competent and may act as target for reactive
      metabolites from TA. To test this hypothesis CYP3A4 and EH were expressed with
      human cytochrome P450 reductase and cytochrome b(5) in a "humanized" yeast
      strain. In the absence of EH only one metabolite was formed. In the presence of
      EH, two additional metabolites were formed, and a time-dependent inactivation of
      EH was detected, suggesting that a reactive oxide derived from TA could alkylate
      the enzyme and trigger an immune response. Antibodies were found to recognize TA
      alkylated EH. Recognition of EH present at the surface of human hepatocytes could
      suggest an (auto)antibody participation in an immune cell destruction.

PMID- 10953046
TI  - Selective activation of the c-Jun N-terminal protein kinase pathway during 4
      hydroxynonenal-induced apoptosis of PC12 cells.
AB  - The by-product of lipid peroxidation, 4-hydroxynonenal (HNE), was shown to cause
      apoptosis in PC12 cells. In this study, we investigated the molecular mechanism
      of HNE-induced apoptosis in these cells. Specifically, we determined the effect
      of HNE on the activities of mitogen-activated protein (MAP) kinases involved in
      early signal transduction. Within 15 to 30 min after HNE treatment, c-Jun N
      terminal protein kinase (JNK) was maximally activated, before it returned to
      control level at 1 h post-treatment. In contrast, activities of extracellular
      signal-regulated kinase and p38 MAP kinase remained unchanged from their baseline
      levels. Stress-activated protein kinase kinase (SEK1), an upstream kinase of JNK,
      was also activated within 5 min after HNE treatment and remained activated for up
      to 60 min. Marked activation of the JNK pathway through SEK1 and apoptosis signal
      regulating kinase 1 (ASK1), an upstream kinase of SEK1, was demonstrated by the
      transient transfection of cDNA for wild-type SEK1 or ASK1 together with JNK into
      COS-7 cells. Furthermore, significant reductions in JNK activation and HNE
      induced cell death were observed when either of the dominant negative mutant of
      SEK1 or ASK1 was cotransfected with JNK. Pretreatment of PC12 cells with a
      survival-promoting agent, 8-(4-chlorophenylthio)-cAMP, prevented both the HNE
      induced JNK activation and apoptosis. Nonaldehyde, a nontoxic aldehyde, neither
      caused apoptosis nor JNK activation. Pretreatment of PC12 cells with SB203580, a
      specific inhibitor of p38 MAP kinase, had no effect on HNE-induced apoptosis. All
      these data suggest that the selective JNK activation by HNE is critical for the
      apoptosis of PC12 cells and that the HNE-mediated apoptosis is likely to be
      mediated through the activation of the ASK1-SEK1-JNK pathway without activation
      of extracellular signal-regulated kinase or p38 MAP kinase.

PMID- 10953048
TI  - Evidence that the proposed novel human "neurokinin-4" receptor is
      pharmacologically similar to the human neurokinin-3 receptor but is not of human
      origin.
AB  - There have been proposals that the tachykinin receptor classification should be
      extended to include a novel receptor, the "neurokinin-4" receptor (NK-4R), which
      has a close homology with the human NK-3 receptor (hNK-3R). We compared the
      pharmacological and molecular biological characteristics of the hNK-3R and NK-4R.
      Binding experiments, with (125)I-[MePhe(7)]-NKB binding to HEK 293 cell membranes
      transiently expressing the hNK-3R (HEK 293-hNK-3R) or NK-4R (HEK 293-NK-4R), and
      functional studies (Ca(2+) mobilization in the same cells) revealed a similar
      profile of sensitivity to tachykinin agonists and antagonists for both receptors;
      i.e., in binding studies with the hNK-3R, MePhe(7)-NKB > NKB > senktide >> NKA =
      Substance P; with the NK-4R, MePhe(7)-NKB > NKB = senktide >> Substance P = NKA;
      and with antagonists, SB 223412 = SR 142801 > SB 222200 >> SR 48968 >> CP 99994
      for both hNK-3R and NK-4R. Thus, the pharmacology of the two receptors was nearly
      identical. However, attempts to isolate or identify the NK-4R gene by using
      various molecular biological techniques were unsuccessful. Procedures, including
      nested polymerase chain reaction studies, that used products with restriction
      endonuclease sites specific for either hNK-3R or NK-4R, failed to demonstrate the
      presence of NK-4R in genomic DNA from human, monkey, mouse, rat, hamster, or
      guinea pig, and in cDNA libraries from human lung, brain, or heart, whereas the
      hNK-3R was detectable in the latter libraries. In view of the failure to
      demonstrate the presence of the putative NK-4R it is thought to be premature to
      extend the current tachykinin receptor classification.

PMID- 10953049
TI  - Probing the interaction of the cytotoxic bisdioxopiperazine ICRF-193 with the
      closed enzyme clamp of human topoisomerase IIalpha.
AB  - Topoisomerase II is an ATP-operated protein clamp that captures a DNA helix and
      transports it through another DNA duplex, allowing chromosome segregation at
      mitosis. A number of cytotoxic bisdioxopiperazines such as ICRF-193 target
      topoisomerase II by binding and trapping the closed enzyme clamp. To investigate
      this unusual mode of action, we have used yeast to select plasmid-borne human
      topoisomerase IIalpha alleles resistant to ICRF-193. Mutations in topoisomerase
      IIalpha of Leu-169 to Phe (L169F) (in the N-terminal ATPase domain) and Ala-648
      to Pro (A648P) (in the core domain) were identified as conferring >50-fold and 5
      fold resistance to ICRF-193 in vivo, respectively. The L169F mutation, located
      next to the Walker A box ATP-binding sequence, resulted in a mutant enzyme
      displaying ICRF-193-resistant topoisomerase and ATPase activities and whose
      closed clamp was refractory to ICRF-193-mediated trapping as an annulus on closed
      circular DNA. These data imply that the mutation interferes directly with ICRF
      193 binding to the N-terminal ATPase gate. In contrast, the A648P enzyme
      displayed topoisomerase activities exhibiting wild-type sensitivity to ICRF-193.
      We suggest that the inefficient trapping of the A648P closed clamp results either
      from the observed increased ATP requirement, or more likely, from lowered salt
      stability, perhaps involving destabilization of ICRF-193 interactions with the B'
      B' interface in the core domain. These results provide evidence for at least two
      different phenotypic classes of ICRF-193 resistance mutations and suggest that
      bisdioxopiperazine action involves the interplay of both the ATPase and core
      domains of topoisomerase IIalpha.

PMID- 10953050
TI  - RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha
      mediated signaling pathways.
AB  - Regulator of G protein signaling (RGS) proteins are a family of approximately 20
      proteins that negatively regulate signaling through heterotrimeric G protein
      coupled receptors. The RGS proteins act as GTPase-activating proteins (GAPs) for
      certain Galpha subunits and as effector antagonists for Gqalpha. Mouse RGS14
      encodes a 547-amino-acid protein with an N-terminal RGS domain, which is highly
      expressed in lymphoid tissues. In this study, we demonstrate that RGS14 is a GAP
      for Gialpha subfamily members and it attenuates interleukin-8 receptor-mediated
      mitogen-activated protein kinase activation. However, RGS14 does not exhibit GAP
      activity toward Gsalpha or Gqalpha nor does it regulate Gsalpha- or Gqalpha
      mediated signaling pathways. Although RGS14 does not act as a GAP for
      G12/13alpha, it impairs c-fos serum response element activation induced by either
      a constitutively active mutant of G13alpha (G13alphaQ226L) or by carbachol
      stimulation of muscarinic type 1 receptors. An RGS14 mutant (EN92/93AA), which
      does not block Gialpha-linked signaling, also inhibits serum response element
      activation. RGS14 localizes predominantly in the cytosol, but it can be recruited
      to membranes by expression of G13alphaQ226L. Although RGS14 is constitutively
      expressed in lymphoid cells, agents that activate B or T lymphocytes further
      enhance its levels. Taken together, our results suggest that signals generated
      after lymphocyte activation may via RGS14 directly impinge on Gialpha- or
      G13alpha-mediated cellular processes in lymphocytes, such as adhesion and
      migration.

PMID- 10953051
TI  - Identification of acylpeptide hydrolase as a sensitive site for reaction with
      organophosphorus compounds and a potential target for cognitive enhancing drugs.
AB  - We describe here the purification and identification of a previously unrecognized
      target for organophosphorus compounds. The target, acylpeptide hydrolase, was
      isolated as a tritiated-diisopropylfluorophosphate-reactive protein from porcine
      brain and purified to homogeneity using a combination of ion-exchange and gel
      filtration chromatography. Biochemical characterization and internal sequence
      analysis confirmed identity. Acylpeptide hydrolase was found to be potently
      inhibited by the organophosphorus compounds chlorpyrifosmethyl oxon, dichlorvos,
      and diisopropylfluorophosphate (20-min IC(50) values of 18.3 +/- 2.0, 118.7 +/-
      9.7, and 22.5 +/- 1.2 nM, respectively). The in vitro sensitivity of acylpeptide
      hydrolase toward these compounds is between six and ten times greater than that
      of acetylcholinesterase (AChE), making it a target of pharmacological and
      toxicological significance. We show that, in vivo, acylpeptide hydrolase is
      significantly more sensitive than AChE to inhibition by dichlorvos and that the
      inhibition is more prolonged after a single dose of inhibitor. Furthermore, using
      dichlorvos as a progressive inhibitor, it was possible to show that acylpeptide
      hydrolase is the only enzyme in the brain capable of hydrolyzing the substrate N
      acetyl-alanyl-p-nitroanilide. A concentration of 154 +/- 27 pmol of acylpeptide
      hydrolase/gram of fresh rat brain was also deduced by specific labeling with
      tritiated-diisopropylfluorophosphate. We also suggest that, by comparison of
      structure-activity relationships, acylpeptide hydrolase may be the target for the
      cognitive-enhancing effects of certain organophosphorus compounds. Acylpeptide
      hydrolase cleaves N(alpha)-acylated amino acids from small peptides and may be
      involved in regulation of neuropeptide turnover, which provides a new and
      plausible mechanism for its proposed cognitive enhancement effect.

PMID- 10953052
TI  - Functional differences between the amino-terminal domains of estrogen receptors
      alpha and beta.
AB  - Human estrogen receptors alpha (ERalpha) and beta (ERbeta) are ligand-inducible
      transcription factors that are highly homologous in their central DNA-binding and
      carboxyl-terminal ligand-binding domains. In contrast, there is very little
      conservation between ERalpha and ERbeta in the amino-terminal domain. Using
      different human cell lines, we show that wild-type ERbeta transcriptional
      activity is lower or similar to that of ERalpha, depending on the cell type.
      Deletion of the amino-terminal domain in both ER subtypes resulted in no or a
      lower decrease of transcriptional activity of ERbeta compared with ERalpha,
      suggesting that the ERbeta amino-terminal domain contains a weaker
      transcriptional activation function-1. Using ERalpha and ERbeta deletion mutants,
      we showed that the amino-terminal transcriptional activity of ERbeta maps to
      amino acids 1-31. Interestingly, this domain contains a six amino-acid motif
      (amino acids 5-10 in human ERbeta) that is part of the ERalpha-activation
      function-1 region (amino acids 49-54 in human ERalpha) and highly conserved among
      all mammalian ERalpha amino-terminal domains. Despite this similarity between the
      two ER subtypes, no autonomous and ligand-independent activity of the ERbeta
      amino-terminal domain was observed in yeast and mammalian cells in contrast to
      ERalpha. This study provides a molecular basis for the difference in
      transcriptional activity between ERalpha and ERbeta and establishes that ERbeta
      contains a structurally and functionally restricted amino-terminal
      transcriptional activity.

PMID- 10953053
TI  - Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium
      channels.
AB  - Retigabine [N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid; D-23129] is a
      novel anticonvulsant, unrelated to currently available antiepileptic agents, with
      activity in a broad range of seizure models. In the present study, we sought to
      determine whether retigabine could enhance current through M-like currents in
      PC12 cells and KCNQ2/Q3 K(+) channels expressed in Chinese hamster ovary cells
      (CHO-KCNQ2/Q3). In differentiated PC12 cells, retigabine enhanced a linopirdine
      sensitive current. The effect of retigabine was associated with a slowing of M
      like tail current deactivation in these cells. Retigabine (0.1 to 10 microM)
      induced a potassium current and hyperpolarized CHO cells expressing KCNQ2/Q3
      cells but not in wild-type cells. Retigabine-induced currents in CHO-KCNQ2/Q3
      cells were inhibited by 60.6 +/- 11% (n = 4) by the KCNQ2/Q3 blocker, linopirdine
      (10 microM), and 82.7 +/- 5.4% (n = 4) by BaCl(2) (10 mM). The mechanism by which
      retigabine enhanced KCNQ2/Q3 currents involved large, drug-induced, leftward
      shifts in the voltage dependence of channel activation (-33.1 +/- 2.6 mV, n = 4,
      by 10 microM retigabine). Retigabine shifted the voltage dependence of channel
      activation with an EC(50) value of 1.6 +/- 0.3 microM (slope factor was 1.2 +/-
      0.1, n = 4 to 5 cells per concentration). Retigabine (0.1 to 10 microM) also
      slowed the rate of channel deactivation, predominantly by increasing the
      contribution of a slowly deactivating tail current component. Our findings
      identify KCNQ2/Q3 channels as a molecular target for retigabine and suggest that
      activation of KCNQ2/Q3 channels may be responsible for at least some of the
      anticonvulsant activity of this agent.

PMID- 10953054
TI  - Characterization of gastrin-releasing peptide and its receptor aberrantly
      expressed by human colon cancer cell lines.
AB  - Gastrin-releasing peptide (GRP) is a mitogen and morphogen important in the
      development of human colon cancers. Although epithelial cells lining the colon do
      not normally express GRP or its receptor (GRP-R), most human tumors express GRP-R
      mRNA. Yet functional protein has only been detected in 24 to 40% of colon
      cancers. To elucidate the reason for the difference between the expression of
      GRP/GRP-R mRNA and protein, we studied nine human colon cancer cell lines.
      Quantitative polymerase chain reaction revealed that all colon cancer cell lines
      expressed similar amounts of mRNA for both GRP as well as GRP-R. Yet binding
      studies using (125)I-Tyr(4)-bombesin detected functional receptors on only five
      of the nine cell lines studied. Conformational fragment-length polymorphism
      analysis indicated that although mRNA for the ligand GRP was never mutated, mRNA
      for the GRP-R was always mutated. Sequencing revealed that the message for GRP-R
      contained between two and seven separate mutations at the nucleotide level. This
      resulted in 14 separate coding mutations, 2 of which were observed in more than
      one cell line. Each mutation was individually recreated by site-directed
      mutagenesis and studied in transiently transfected Chinese hamster ovary-K1
      cells. Alteration of Pro(145) into a tyrosine, of Val(317) into a glutamic acid,
      and insertion of a 32-nucleotide segment resulting in a frameshift distal to
      Asp(137) all resulted in GRP receptors incapable of binding ligand. Thus, these
      data indicate that human colon cancers commonly express GRP and GRP-R mRNA but
      that receptor mutations account for the failure of functional protein to be
      generated.

PMID- 10953055
TI  - Pertussis toxin inhibits cholecystokinin- and epidermal growth factor-induced
      mitogen-activated protein kinase activation by disinhibition of the cAMP
      signaling pathway and inhibition of c-Raf-1.
AB  - Pertussis toxin (PTx), which inactivates G(i/o) type G proteins, is widely used
      to investigate the involvement of G(i/o) proteins in signal transduction.
      Activation of extracellular-regulated kinases 1 and 2 (ERK1/2) by G protein
      coupled receptors has been described to occur either through a PTx-insensitive
      pathway involving activation of phospholipase C and protein kinase C (PKC), or
      through a PTx-sensitive pathway involving G(i)betagamma-mediated activation of
      Src. Cholecystokinin (CCK) activates ERK1/2 by a PKC-dependent, and thus
      presumably PTx-insensitive, pathway. However, CCK has recently been shown to
      induce activation of G(i) proteins in addition to G(q/11). In the present study,
      PTx partially inhibited CCK-induced ERK1/2 activation in pancreatic AR42J cells,
      although activation of phospholipase C was not reduced. PTx also inhibited ERK1/2
      activation in response to the PKC activator 12-O-tetradecanoylphorbol-13-acetate
      (TPA) and epidermal growth factor (EGF) as well as activation of c-Raf-1 by EGF
      and CCK. In contrast, PTx, CCK, and EGF had only minor effects on A-Raf and B-Raf
      activity. Forskolin, a direct activator of adenylyl cyclase, inhibited CCK- and
      EGF-induced activation of c-Raf-1 and ERK1/2 in a manner similar to that of PTx.
      In PTx-treated cells, the cAMP content was increased and forskolin did not
      further inhibit CCK- and EGF-induced activation of c-Raf-1 or ERK1/2. In
      conclusion, the present study shows that PTx-sensitivity of receptor-induced
      ERK1/2 activation could be a consequence of disinhibition of the adenylyl cyclase
      signaling pathway, which in turn causes inhibition of c-Raf-1 activation rather
      than indicating involvement of a PTx-sensitive G protein in this signaling
      pathway.

PMID- 10953056
TI  - Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate
      receptors.
AB  - Conantokin G (Con G) is a 17-amino-acid peptide antagonist of N-methyl-D
      aspartate (NMDA) receptors isolated from the venom of the marine cone snail,
      Conus geographus. The mechanism of action of Con G has not been well defined;
      both competitive and noncompetitive interactions with the NMDA-binding site have
      been proposed. In this study the mechanism of action and subunit selectivity of
      Con G was examined in whole-cell voltage-clamp recordings from cultured neurons
      and in two electrode voltage-clamp recordings from Xenopus oocytes expressing
      recombinant NMDA receptors. Con G was a potent and selective antagonist of NMDA
      evoked currents in murine cortical neurons (IC(50) = 480 nM). The slow onset of
      Con G block could be prevented by coapplication with high concentrations of NMDA
      or of the competitive antagonist (RS)-3-(2-carboxypiperazine-4-yl)-propyl-1
      phosphonic acid. Furthermore, in oocytes expressing NR1a/NR2B receptors, Con G
      produced a rightward shift in the concentration-response curve for NMDA,
      providing support for a competitive interaction with the NMDA-binding site. Con G
      produced an apparent noncompetitive shift in the concentration-response curve for
      spermine potentiation of NMDA responses, but this was due to spermine-induced
      enhancement of Con G block. Spermine produced a similar enhancement of DL-2-amino
      S-phosphopentanoic acid block. Finally, Con G selectively blocked NMDA receptors
      containing the NR2B subunit. These results demonstrate that Con G is a subunit
      specific competitive antagonist of NMDA receptors. The unique subunit selectivity
      profile of Con G may explain its favorable in vivo profile compared with
      nonselective NMDA antagonists.

PMID- 10953057
TI  - Communication between multiple drug binding sites on P-glycoprotein.
AB  - P-glycoprotein, a member of the ATP-binding cassette transporter family, is able
      to confer resistance on tumors against a large number of functionally and
      chemically distinct cytotoxic compounds. Several recent investigations suggest
      that P-glycoprotein contains multiple drug binding sites rather than a single
      site of broad substrate specificity. In the present study, radioligand-binding
      techniques were used to directly characterize drug interaction sites on P
      glycoprotein and how these multiple sites interact. The drugs used were
      classified as either 1) substrates, which are known to be transported by P
      glycoprotein (e.g., vinblastine) or 2) modulators, which alter P-glycoprotein
      function but are not themselves transported by the protein (e.g., XR9576). Drug
      interactions with P-glycoprotein were either competitive, at a common site, or
      noncompetitive, and therefore at distinct sites. Based on these data, we can
      assign a minimum of four drug binding sites on P-glycoprotein. These sites fall
      into two categories: transport, at which translocation of drug across the
      membrane can occur, and regulatory sites, which modify P-glycoprotein function.
      Intriguingly, however, some modulators interact with P-glycoprotein at a
      transport site rather than a regulatory site. The pharmacological data also
      demonstrate that both transport and regulatory sites are able to switch between
      high- and low-affinity conformations. The multiple sites on P-glycoprotein
      display complex allosteric interactions through which interaction of drug at one
      site switches other sites between high- or low-affinity conformations. The data
      are discussed in terms of a model for the mechanism of transport by P
      glycoprotein.

PMID- 10953058
TI  - Tetrahydrobiopterin is released from and causes preferential death of
      catecholaminergic cells by oxidative stress.
AB  - The underlying cause of the selective death of the nigral dopaminergic neurons in
      Parkinson's disease is not fully understood. Tetrahydrobiopterin (BH4) is
      synthesized exclusively in the monoaminergic, including dopaminergic, cells and
      serves as an endogenous and obligatory cofactor for syntheses of dopamine and
      nitric oxide. Because BH4 contributes to the syntheses of these two potential
      oxidative stressors and also undergoes autoxidation, thereby producing reactive
      oxygen species, it was possible that BH4 may play a role in the selective
      vulnerability of dopaminergic cells. BH4 given extracellularly was cytotoxic to
      catecholamine cells CATH. a, SK-N-BE(2)C, and PC12, but not to noncatecholamine
      cells RBL-2H3, CCL-64, UMR-106-01, or TGW-nu-1. This was not caused by increased
      dopamine or nitric oxide, because inhibition of their syntheses did not attenuate
      the damage and BH4 did not raise their cellular levels. Dihydrobiopterin and
      biopterin were not toxic, indicating that the fully reduced form is responsible.
      The toxicity was caused by generation of reactive oxygen species, because
      catalase, superoxide dismutase, and peroxidase protected the cells from the BH4
      induced demise. Furthermore, thiol agents, such as reduced glutathione,
      dithiothreitol, beta-mercaptoethanol, and N-acetylcysteine were highly
      protective. The BH4 toxicity was initiated extracellularly, because elevation of
      intracellular BH4 by sepiapterin did not result in cell damage. BH4 was
      spontaneously released from the cells of its synthesis to a large extent, and the
      release was not further enhanced by calcium influx. This BH4-induced cytotoxicity
      may represent a mechanism by which selective degeneration of dopaminergic
      terminals and neurons occur.

PMID- 10953059
TI  - Viral entry as the primary target for the anti-HIV activity of chicoric acid and
      its tetra-acetyl esters.
AB  - The antiviral activity of L-chicoric acid against HIV-1 has been attributed
      previously to the inhibition of HIV-1 integration. This conclusion was based on
      the inhibition of integrase activity in enzymatic assays and the isolation of a
      resistant HIV strain with a mutation (G140S) in the integrase gene. Here we show
      that the primary antiviral target of L-CA and its analogs in cell culture is
      viral entry. L- and D-chicoric acid (L-CA and D-CA) and their respective tetra
      acetyl esters inhibit the replication of HIV-1 (III(B) and NL4.3) and HIV-2 (ROD)
      in MT-4 cells at a 50% effective concentration (EC(50)) ranging from 1.7 to 70.6
      microM. In a time-of-addition experiment, L-CA, D-CA, L-CATA, and D-CATA were
      found to interfere with an early event in the viral replication cycle. Moreover,
      L-CA, D-CA, and their analogs did not inhibit the replication of virus strains
      that were resistant toward polyanionic and polycationic compounds at subtoxic
      concentrations. Furthermore, HIV-1 strains resistant to L-CA and D-CA were
      selected in the presence of L-CA and D-CA, respectively. Mutations were found in
      the V2, V3, and V4 loop region of the envelope glycoprotein gp120 of the L-CA and
      D-CA-resistant NL4.3 strains that were not present in the wild-type NL4.3 strain.
      Recombination of the gp120 gene of the L-CA and D-CA resistant strain in a NL4.3
      wild-type molecular clone fully rescued the phenotypic resistance toward L-CA and
      D-CA. No significant mutations were detected in the integrase gene of the drug
      resistant virus strains. Although inhibition of HIV integrase activity by L-CA
      and its derivatives was confirmed in an oligonucleotide-driven assay, integrase
      carrying the G140S mutation was inhibited to the same extent as the wild-type
      integrase.

PMID- 10953060
TI  - Acridinecarboxamide topoisomerase poisons: structural and kinetic studies of the
      DNA complexes of 5-substituted 9-amino-(N-(2-dimethylamino)ethyl)acridine-4
      carboxamides.
AB  - For a series of antitumor-active 5-substituted 9-aminoacridine-4-carboxamide
      topoisomerase II poisons, we have used X-ray crystallography and stopped-flow
      spectrophotometry to explore relationships between DNA binding kinetics,
      biological activity, and the structures of their DNA complexes. The structure of
      5-F-9-amino-[N-(2-dimethylamino)ethyl]-acridine-4-carboxamide bound to
      d(CGTACG)(2) has been solved to a resolution of 1.55 A in space group P6(4). A
      drug molecule intercalates between each of the CpG dinucleotide steps, its
      protonated dimethylamino group partially occupying positions close to the N7 and
      O6 atoms of guanine G2 in the major groove. A water molecule forms bridging
      hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same
      guanine. Intercalation unwinds steps 1 and 2 by 12 degrees and 8 degrees,
      respectively compared with B-DNA, whereas the central TpA step is overwound by 10
      degrees. Nonphenyl 5-substituents, on average, decrease mean DNA dissociation
      rates by a factor of three, regardless of their steric, hydrophobic, H-bonding,
      or electronic properties. Cytotoxicity is enhanced on average 4-fold and binding
      affinities rise by 3-fold, thus there is an apparent association between
      kinetics, affinity, and cytotoxicity. Taken together, the structural and kinetic
      studies imply that the main origin of this association is enhanced stacking
      interactions between the 5-substituent and cytosine in the CpG binding site.
      Ligand-dependent perturbations in base pair twist angles and their consequent
      effects on base pair-base pair stacking interactions may also contribute to the
      stability of the intercalated complex. 5-Phenyl substituents modify dissociation
      rates without affecting affinities, and variations in their biological activity
      are not correlated with DNA binding properties, which suggests that they interact
      directly with the topoisomerase protein.

PMID- 10953061
TI  - A comparison of critical velocity estimates to actual velocities in predicting
      simulated rowing performance.
AB  - The most accurate critical velocity (CV) estimate for the prediction of velocity
      during a simulated 2,000-m rowing race and the relationship to aerobic power were
      studied. Sixteen male rowers completed randomized maximal exertion trials (200,
      400, 600, 800, 1,000, and 1,200 m), a maximal oxygen consumption (VO(2)max) on a
      Concept II rowing machine, and an actual 2,000-m simulated rowing race. Three
      mathematical models were applied to 4 rowing distance combinations producing 12
      CV estimates. Seven of the 12 possible CV estimates were not significantly
      different from actual 2,000-m velocity. Comparison of the 3 CV models using all 6
      trial distances revealed that the nonlinear model produced a CV estimate lower
      than the 2 linear CV models. CV was significantly correlated to VO(2)max (r =
      0.91) and the mean velocity achieved during the 2,000-m simulated rowing race (r
      = 0.97). VO(2)max was significantly correlated to 2,000-m simulated rowing race
      velocity (r = 0.93).

PMID- 10953062
TI  - Health-related fitness, physical activity, and history of back pain.
AB  - The relationship between history of back pain and measurements of both health
      related fitness and physical activity participation was examined in 233 males and
      287 females aged 15-69 years. Participants were divided by gender into those
      reporting no history (NH) or a history (H) of recurring back pain. Analysis of
      variance indicated that trunk flexion, back extensor endurance, and physical
      activity participation were significantly higher for NH and waist girth
      significantly lower for NH in both genders. In females, mean abdominal muscular
      endurance was significantly higher in NH. Forward stepwise discriminant function
      analyses indicated that the best discriminators between NH and H were back
      extensor endurance and physical activity participation in both genders and waist
      girth in females. These findings support using measurements of trunk flexion,
      abdominal muscular endurance, back extensor endurance, physical activity
      participation, and waist girth as indicators of back fitness in the evaluation of
      back health.

PMID- 10953063
TI  - Physiological responses to cycling for 60 minutes at maximal lactate steady
      state.
AB  - Changes in physiological variables during a 60-min continuous test at maximal
      lactate steady state (MLSS) were studied using highly conditioned cyclists (1
      female and 9 males, aged 28.3 +/- 8.1 years). To determine power at MLSS, we
      tested at 8-min increments and interpolated the power corresponding to a blood
      lactate value of 4 mmol/L. During the subsequent 60-min exercise at MLSS, we
      observed a sequential increase of physiological parameters, in contrast to stable
      blood lactate. Heart rate drifted upward from beginning to end of exercise. This
      became statistically significant after 30 min. From 10-60 min of exercise, a
      change of +12.6 +/- 3.2 bpm was noted. Significant drift was seen after 30 min
      for the respiratory exchange ratio, after 40 min for the rate of perceived
      exertion using the Borg scale, and after 50 min for % VO(2)max/kg and minute
      ventilation. This slow component of VO(2)max may be the result of higher
      recruitment of type II fibers.

PMID- 10953064
TI  - Electromyographic and mechanomyographic responses.
AB  - The purpose of the present study was to determine the electromyographic (EMG) and
      mechanomyographic (MMG) responses to cycle ergometry at critical power (CP).
      Seven moderately active males (25 +/- 3 years) completed a 60-min trial at their
      CP estimated from a nonlinear, 3 parameter regression model. EMG and MMG
      amplitudes were recorded from the vastus lateralis during 60-min continuous rides
      at CP. The mean CP was 175 +/- 25 W, which represented 56 +/- 5% of the subjects'
      peak power outputs. The results indicated that the slope coefficient for the EMG
      amplitude versus time relationship was not significantly different from zero;
      however, MMG amplitude decreased significantly over the 60 min. This dissociation
      between the electrical (EMG) and mechanical (MMG) aspects of muscular activity
      during cycle ergometry may be due to neuromuscular changes associated with
      "muscle wisdom" or changes in muscular compliance.

PMID- 10953066
TI  - Estrogen and gender effects on muscle damage, inflammation, and oxidative stress.
AB  - Information suggests that there may be gender-based differences in skeletal
      muscle responses to damaging exercise. Evidence demonstrates that estrogen has
      strong antioxidant properties and may be an important factor in maintaining
      postexercise membrane stability and limiting creatine kinase (CK) leakage from
      damaged muscle in female animals. Research demonstrates effects of estrogen and
      possible gender differences in other morphological and biochemical indices of
      postexercise muscle damage and leukocyte invasion. Nevertheless, there are
      conflicting findings suggesting that in some in vivo exercise models, estrogen
      administration has limited ability to affect exercise-induced oxidative stress
      and muscle damage and may cause loss of tissue vitamin C. Gender differences
      appear to exist in tissue levels of other important antioxidants such as vitamin
      E and glutathione. More research is needed to fully define the potential for
      estrogen to influence postexercise muscle damage and the inflammatory response
      and to determine the mechanisms by which it may operate.

PMID- 10953067
TI  - Sex differences in substrate metabolism and energy homeostasis.
AB  - Females differ remarkably from males in the mechanisms that regulate substrate
      utilization and energy homeostasis. Females appear to be less affected in terms
      of growth and loss of body tissues when subjected to chronic periods of negative
      energy balance. The physiological trade-off appears to be a stronger propensity
      toward retention of fat mass during times of energy surfeit. The mechanism(s)
      that account for sex differences in energy metabolism are not known but most
      likely involve the sex steroids. Recent discoveries in the areas of endocrinology
      and metabolism may provide new insights into differences in the control of food
      intake and energy conservation between the sexes. Finally, the study of the
      mechanism(s) involved in the regulation of skeletal muscle lipid metabolism
      represents a new frontier in skeletal muscle bioenergetics, and new discoveries
      may provide further explanations for the observed sex differences in substrate
      utilization and response(s) to alterations in energy homeostasis.

PMID- 10953068
TI  - Gender differences in substrate metabolism during endurance exercise.
AB  - Females show a lower respiratory exchange ratio (RER) than males during
      submaximal endurance exercise, which translates into a proportionately lower
      carbohydrate and higher fat oxidation. Data from rodents show that 17-beta
      estradiol may mediate these metabolic differences. 17-beta-estradiol
      supplementation in humans is less convincing; however, two studies found a
      reduction in glucose rate of appearance during exercise. No difference is found
      between genders in muscle glycogen content; however, lipid content in muscle is
      higher in females. Evidence shows that short chain OH-acyl CoA-dehydrogenase
      (SCHAD) maximal enzyme activity is higher in females. The rate of leucine
      oxidation is lower in females at rest and during endurance exercise. This is not
      apparently related to gender differences in branched chain-2-oxo-dehydrogenase
      (BCOAD) activity in skeletal muscle, which may implicate hepatic control.
      Important muscle proteins to examine in future research are hormone sensitive
      lipase, the enzymes of beta-oxidation, and fatty acid transporters.

PMID- 10953069
TI  - Our obligation to the next generation.

PMID- 10953071
TI  - Care emerges from chaos

PMID- 10953070
TI  - Evidence-based nursing: what it is and what it isn't.

PMID- 10953072
TI  - Robots and nurses.

PMID- 10953073
TI  - We need to use first person pronouns in our writing.

PMID- 10953074
TI  - End-of-life decisions in adult intensive care: current research base 158 and
      directions for the future.

PMID- 10953075
TI  - Why hospital patients do and do not execute an advance directive.

PMID- 10953076
TI  - A call to intraprofessional alliances.

PMID- 10953077
TI  - Levels of theoretical thinking in nursing.

PMID- 10953078
TI  - A new collaborative opportunity: the John A. Hartford Foundation and the American
      Academy of Nursing.

PMID- 10953079
TI  - The cytochrome P450ALK multigene family of an n-alkane-assimilating yeast,
      Yarrowia lipolytica: cloning and characterization of genes coding for new CYP52
      family members.
AB  - Genes encoding cytochromes P450 of the CYP52 family in the n-alkane-assimilating
      yeast Yarrowia lipolytica have been cloned and analyzed. Degenerate PCR primers
      which were designed for the conserved amino acid sequences of cytochromes P450ALK
      of Candida species were used for amplification and isolation of genes encoding
      P450ALK from a genomic DNA library of Y. lipolytica CX161-1B. Seven new genes
      (YlALK2-YlALK8) were isolated. Five of the seven YlALK genes were induced by n
      alkane under the culture conditions used in this study, whereas their expression
      was strictly repressed by glycerol but not by glucose, similar to the case of
      YlALK1, reported previously. Disruption of YlALK2, YlALK3, YlALK4 or YlALK6 did
      not change the growth of Y. lipolytica on medium containing n-alkanes of various
      chain lengths. A mutant with disruptions in both YlALK1 and YlALK2 did not grow
      well on n-hexadecane, whereas one with disruptions in both YlALK1 and YlALK3,
      which has the same phenotype as the YlALK1 singly disrupted mutant, grew well on
      n-hexadecane. These results suggest that the presence of multiple P450ALK species
      is a rather common phenomenon among the n-alkane-assimilating yeasts and that in
      the n-alkane assimilation of Y. lipolytica, YlALK1 functions to assimilate n
      decane and longer molecules, whereas YlALK2 is involved in the assimilation of
      molecules longer than n-dodecane; other YlALKs are not significantly involved in
      the assimilation of C10-C16 n-alkanes.

PMID- 10953080
TI  - Gene disruption and basic phenotypic analysis of nine novel yeast genes from
      chromosome XIV.
AB  - In this work, we describe the disruption of nine ORFs of S. cerevisiae (YNL123w,
      YNL119w, YNL115c, YNL108c, YNL110c, YNL124w, YNL233w, YNL232w and YNL231c) in two
      genetic backgrounds: FY1679 and CEN.PK2. For the construction of the deletant
      strains, we used the strategy of short flanking homology (SFH) PCR. The SFH
      deletion cassette was made by PCR amplification of the KanMX4 module with primers
      containing a 5' region of 40 bases homologous to the target yeast gene and with a
      3' region of 20 bases homologous to pFA6a-KanMX4 MCS. Sporulation and tetrad
      analysis of heterozygous deletants revealed that YNL110c, YNL124w and YNL232w are
      essential genes. The subcellular localization of the protein encoded by the
      essential gene YNL110c was investigated using the green fluorescent protein (GFP)
      approach, revealing a nuclear pattern. Basic phenotypic analysis of the non
      essential genes revealed that the growth of ynl119w delta haploid cells was
      severely affected at 37 degrees C in N3 medium, indicating that this gene is
      required at high temperatures with glycerol as a non-fermentable substrate. The
      ynl233w delta haploid cells also showed a particular phenotype under light
      microscopy and were studied in detail in a separate work.

PMID- 10953081
TI  - Cloning, sequencing, and expression of H.a.YNR1 and H.a.YNI1, encoding nitrate
      and nitrite reductases in the yeast Hansenula anomala.
AB  - A single Hansenula anomala genomic DNA fragment containing the genes H.a.YNR1
      (yeast nitrate reductase) and H.a.YNI1 (yeast nitrite reductase) encoding nitrate
      and nitrite reductase, respectively, was isolated from a lambda EMBL3 genomic DNA
      library. As probe, a 3.2 kb DNA fragment isolated from a lambda gt11 H. anomala
      genomic DNA library screened with antiserum anti-NR from H. anomala was used. H.
      a.YNR1 and H.a.YNI1 genes are separated by 473 bp and encode putative proteins of
      870 and 1077 amino acids, respectively, with great similarity to nitrate and
      nitrite reductases from other organisms. Northern blot analysis revealed that
      both genes are highly expressed in nitrate, very low in nitrate plus ammonium,
      and no expression was detected in ammonium or nitrogen-free media. Levels of
      nitrate reductase and nitrite reductase were very low or undetectable by Western
      blot analysis in nitrogen-free and ammonium media, whereas both proteins were
      present in nitrate and ammonium plus nitrate media. The nucleotide sequence
      Accession No. is AF123281.

PMID- 10953082
TI  - Cells of the yeast Saccharomyces cerevisiae are transformable by DNA under non
      artificial conditions.
AB  - Transformants of bakers' yeast (Saccharomyces cerevisiae) can be generated when
      non-growing cells metabolize sugars (without additional nutrients) in the
      presence of plasmid DNA. These results suggest that there is a mechanism by which
      DNA can naturally be taken up by the yeast cell. Natural transformation does not
      take place in common complete or minimal yeast culture media such as YPD and YNB.
      The starvation conditions used in our experiments thus seem to be an important
      prerequisite for such transformation events.

PMID- 10953083
TI  - GAP1, a novel selection and counter-selection marker for multiple gene
      disruptions in Saccharomyces cerevisiae.
AB  - We report on the use of a new homologous marker for use in multiple gene
      deletions in S. cerevisiae, the general amino acid permease gene (GAP1). A GAP1
      strain can utilize L-citrulline as the sole nitrogen source but cannot grow in
      the presence of the toxic amino acid D-histidine. L-citrulline as well as D
      histidine uptake is mediated solely by the general amino acid permease, and a
      gap1 strain is therefore able to grow in the presence of D-histidine but cannot
      utilize L-citrulline. Gene disruption is effected by transforming a gap1 strain
      with a gene cassette generated by PCR, containing GAP1 flanked by short (60 bp)
      stretches of the gene in question. Through homologous recombination, the cassette
      will integrate into the target gene, which is thus replaced by GAP1, and mutants
      are selected for on minimal L-citrulline medium. When propagated under non
      selective conditions, some cells will lose the GAP1 gene. This is caused by
      recombination between two Ashbya gossypii AgLEU2 [corrected] direct repeats
      embracing GAP1, and will result in a sub-population of gap1 cells. Such cells are
      selected on a medium containing D-histidine, and may subsequently be used for a
      second gene disruption. Hence, multiple gene disruptions can be made fast,
      cheaply and easily in a gap1 strain, with two positive selection steps for each
      disruption.

PMID- 10953084
TI  - Evaluation of the CaMAL2 promoter for regulated expression of genes in Candida
      albicans.
AB  - An expression vector (CIp10-MAL2p) for use in Candida albicans has been
      constructed in which a gene of interest can be placed under the control of the
      CaMAL2 maltase promoter and stably integrated at the CaRP10 locus. Using this
      vector to express the Candida URA3 gene from the CaMAL2 promoter, we have
      demonstrated tight regulation of CaURA3 expression by carbon source. Thus under
      conditions when the CaMAL2 promoter is not induced, expression of Candida URA3
      was unable either to complement a C. albicans ura3 mutation or to confer
      sensitivity to 5-fluoroorotic acid, a compound which is highly toxic to URA3
      strains. Since Candida albicans is an obligate diploid organism, analysis of gene
      function requires manipulation of both copies of any gene of interest. Our
      expression vector provides a strategy by which the remaining copy of a gene of
      interest can be placed under CaMAL2 promoter control in a strain where the first
      copy has been deleted, permitting analysis of gene function by manipulation of
      carbon source. CIp10-MAL2p should therefore provide a useful means for functional
      analysis of genes in C. albicans. We have used this strategy with C. albicans
      DPB2 to demonstrate that the gene is essential and that loss of function leads
      cells to adopt a hypha-like morphology as they cease proliferation.

PMID- 10953085
TI  - Relationship of codon bias to mRNA concentration and protein length in
      Saccharomyces cerevisiae.
AB  - In 1982, Ikemura reported a strikingly unequal usage of different synonymous
      codons, in five Saccharomyces cerevisiae nuclear genes having high protein
      levels. To study this trend in detail, we examined data from three independent
      studies that used oligonucleotide arrays or SAGE to estimate mRNA concentrations
      for nearly all genes in the genome. Correlation coefficients were calculated for
      the relationship of mRNA concentration to four commonly used measures of
      synonymous codon usage bias: the codon adaptation index (CAI), the codon bias
      index (CBI), the frequency of optimal codons (F(op)), and the effective number of
      codons (N(c)). mRNA concentration was best approximated as an exponential
      function of each of these four measures. Of the four, the CAI was the most
      strongly correlated with mRNA concentration (r(s)=0.62+/-0.01, n=2525, p<10(
      17)). When we controlled for CAI, mRNA concentration and protein length were
      negatively correlated (partial r(s)=-0.23+/-0.01, n=4765, p<10(-17)). This may
      result from selection to reduce the size of abundant proteins to minimize
      transcriptional and translational costs. When we controlled for mRNA
      concentration, protein length and CAI were positively correlated (partial
      r(s)=0.16+/-0.01, n=4765, p<10(-17)). This may reflect more effective selection
      in longer genes against missense errors during translation. The correlation
      coefficients between the mRNA levels of individual genes, as measured by
      different investigators and methods, were low, in the range r(s)=0.39-0.68.

PMID- 10953086
TI  - Inheritance of suppressors of the drug sensitivity of a NSR1 deleted yeast
      strain.
AB  - The NSR1 gene product is involved in ribosomal RNA production and ribosome
      assembly in Saccharomyces cerevisiae. Yeast strains carrying a deletion of the
      NSR1 gene have a defect in rRNA processing, an aberrant ribosome profile and are
      sensitive to the drug paromomycin. This paper reports the isolation and
      characterization of spontaneous suppressors of the paromomycin sensitivity. Such
      suppressors could be isolated at very high frequency and do not exhibit
      straightforward single-gene inheritance patterns. The suppressors are not
      influenced by non-Mendelian factors such as psi or rho. Through a replacement of
      chromosomal rDNA with a plasmid rDNA system, I show that suppression of
      paromomycin sensitivity is mediated by rDNA. Swapping wild-type plasmid rDNA for
      chromosomal rDNA can reverse the suppression, but the effect does not appear to
      be due to amplification of rDNA or amplification of a pre-existing mutant rDNA
      copy.

PMID- 10953088
TI  - Immunology in Poland.

PMID- 10953087
TI  - vga Mutants of Kluyveromyces lactis show cell integrity defects.
AB  - We studied the cell wall alterations that occur in mutants of Kluyveromyces
      lactis impaired in glycosylation. The mutants belong to four complementation
      groups named vga1 to vga4 (vanadate glycosylation affected), characterized by
      sodium orthovanadate resistance and alteration of the glycosylation profile of
      native invertase. A drastic reduction of the alkali-soluble fraction of the beta
      D-glucan was observed in vga1, vga2 and vga3 cells, accompanied by an increase in
      the chitin content of the cell wall. In vga4 cells, both beta-D-glucan fractions
      (alkali-soluble and alkali-insoluble) were reduced to about half of the
      corresponding wild-type value but the chitin content was normal. A protein
      related to Fks1p, the catalytic subunit of the major 1,3-beta-D-glucan synthase
      of S. cerevisiae, was detected in K. lactis. The amount of this Fks1p-like
      protein increased 7-10 times in vga1, vga2 and vga3 mutants as compared to wild
      type cells; the same strains released significant amounts of beta-D-glucan in the
      culture supernatant. These mutations also resulted in abnormally thick cell walls
      with conspicuous irregularities in the structure, as revealed by electron
      microscopy and by an altered resistance to Zymolyase. The observed high
      responsiveness of cell wall phenotypes to alterations of glycosylation make K.
      lactis an attractive system for studying the interconnections between these
      processes.

PMID- 10953089
TI  - Cytokines and chemokines in T lymphopoiesis and T-cell effector function.

PMID- 10953090
TI  - Chemokines in inflammation and immunity.
AB  - Since the discovery of interleukin 8 (IL-8), about 50 chemokines have been
      characterized. Originally, they were considered as inducible mediators of
      inflammation, but in recent years, several chemokines have been identified that
      are expressed constitutively and function in the physiological traffic and homing
      of leukocytes.

PMID- 10953091
TI  - Human NK-cell receptors.

PMID- 10953092
TI  - Immunity 2000.

PMID- 10953093
TI  - Etiopathogenesis of systemic lupus erythematosus.

PMID- 10953094
TI  - Adenovirus vectors for high-efficiency gene transfer into mammalian cells.

PMID- 10953095
TI  - Dissecting affinity maturation: a model explaining selection of antibody-forming
      cells and memory B cells in the germinal centre.
AB  - Until recently, the relationship between apoptosis, selection in the germinal
      centre (GC) and production of high-affinity antibody-forming cells (AFCs) and
      memory B cells has been unclear. Here, Tarlinton and Smith present a model that
      accounts for the switch in GC production from high-affinity AFCs to memory B
      cells, and explain how Bcl-2, an inhibitor of apoptosis, can influence memory
      cells but not bone marrow AFCs.

PMID- 10953096
TI  - Follicular dendritic cells in TSE pathogenesis.
AB  - The pathogenesis of transmissible spongiform encephalopathies (TSEs) often
      includes a replication phase in lymphoid tissues before infection spreads to the
      central nervous system. Recent studies show that the follicular dendritic cells
      of the germinal centres are critical for this replication. These cells are
      therefore potential targets for therapy or prophylaxis in natural TSEs, such as
      variant Creutzfeldt-Jakob disease.

PMID- 10953097
TI  - Viral mechanisms of immune evasion.
AB  - During the millions of years they have coexisted with their hosts, viruses have
      learned how to manipulate host immune control mechanisms. Viral gene functions
      provide an overview of many relevant principles in cell biology and immunology.
      Our knowledge of viral gene functions must be integrated into virus-host
      interaction networks to understand viral pathogenesis, and could lead to new anti
      viral strategies and the ability to exploit viral functions as tools in medicine.

PMID- 10953098
TI  - Antigen-processing machinery breakdown and tumor growth.
AB  - Defects in the major histocompatibility complex (MHC) class I antigen-processing
      machinery (APM) have been described in tumors of different histology. Murine data
      suggest that defects in the MHC class II APM might also be associated with
      malignant transformation of human cells. This article describes the
      pathophysiology of the MHC class I and II APM, reviews APM abnormalities in tumor
      cells and discusses their role in the escape of tumor cells from in vitro
      recognition by T cells.

PMID- 10953099
TI  - Immunopathology of schistosomiasis mansoni in mice and men.

PMID- 10953100
TI  - Evaluation of the biocompatibility of two new diamond-like stent coatings (Dylyn)
      in a porcine coronary stent model.
AB  - Hydrogenated diamond-like carbon films (DLC, a-C:H), deposited using plasma
      assisted or ion beam-assisted techniques, offer great potential as self
      lubricating coatings in many tribological applications. Additionally, studies on
      biocompatibility have shown that DLC is an inert, impervious hydrocarbon with
      properties suitable for use in the biomedical field. One particular class of
      modified DLC coatings are diamond-like nanocomposite coatings (DLN or Dylyn ,
      Bekaert, Kortrijk, Belgium), which offer promising solutions for many industrial
      applications. In this study, the biocompatibility of two diamond-like stent
      coatings are evaluated in a porcine coronary stent model. METHODS: Either coated
      or non-coated stents were randomly implanted in two coronary arteries of 20 pigs
      so that each group contained 13 stented arteries. Pigs underwent a control
      angiogram at 6 weeks and were then sacrificed. Quantitative coronary analysis
      before, immediately after stent implantation, and at 6 weeks was performed using
      the semi-automated Polytron 1000 system (Siemens, Erlangen, Germany). Morphometry
      was performed using a computerized morphometric program. Angiographic analysis
      showed similar baseline selected arteries and post-stenting diameters. At 6-week
      follow-up, there was no significant difference in minimal stent diameter.
      Histopathology revealed a similar injury score in the 3 groups. Inflammation was
      significantly increased in the DLN-DLC coating group. Thrombus formation was
      significantly decreased in both coated stent groups. Neointimal hyperplasia was
      decreased in both coated stent groups; however, the difference with the non
      coated stents was not statistically significant. Area stenosis was lower in the
      DLN-coated stent group than in the control group (41 +/- 17% vs. 54 +/- 15%; p =
      0.06). CONCLUSION: The results indicate that the diamond-like nanocomposite stent
      coatings are compatible, resulting in decreased thrombogenicity and decreased
      neointimal hyperplasia. Covering this coating with another diamond-like carbon
      film (DLC) resulted in an increased inflammatory reaction and no additional
      advantage compared to the single-layer diamond-like nanocomposite coating.

PMID- 10953101
TI  - Effectiveness and complications of vascular access closure devices after
      interventional procedures.
AB  - BACKGROUND: Vascular closure devices are designed to obtain a fast hemostasis of
      the vascular access site after diagnostic and interventional procedures. This
      result should be obtained with a low incidence of complications. METHODS: A
      retrospective, non-randomized study was performed to evaluate the success rate
      and vascular complications associated with the use of two different vascular
      sealing devices [Angio-Seal (Daig Corporation, Minnetonka, Minnesota) and Prostar
      (Perclose, Inc., Redwood City, California)] after interventional procedures.
      RESULTS: Eight-hundred and twenty-seven devices were used (245 Angio-Seal and 582
      Prostar). Angio-Seal success rate was 92% with a 2.5% rate of vascular
      complications; Prostar success rate was 89% with a 3.4% rate of vascular
      complications. Multivariate logistic regression analysis identified advanced age
      (p < 0.05) and lower weight (p < 0.05) as independent predictors of vascular
      complications associated with Angio-Seal use, while diabetes (p < 0.05) was found
      to be a predictor of vascular complications in the Prostar group. Abciximab use
      and larger sheath size were not associated with an increased probability of
      vascular complications. CONCLUSION: Angio-Seal and Prostar obtain a fast vascular
      access hemostasis after interventional procedures, with a low incidence of major
      vascular complications.

PMID- 10953102
TI  - Should vascular access closure devices be routine after interventional
      procedures?

PMID- 10953103
TI  - Balloon coarctation angioplasty: follow-up of 103 patients.
AB  - OBJECTIVE: To evaluate the role of balloon coarctation angioplasty (BCA) in the
      management of patients with native coarctation of the aorta. BACKGROUND: BCA has
      emerged as an alternative to surgery for patients with native coarctation of the
      aorta. However, its role remains controversial. METHODS: Over a 7-year period,
      103 patients undergoing BCA were enrolled in the study. Hemodynamic evaluation
      was obtained at baseline and immediately following BCA; 75% of patients returned
      for follow-up evaluation at 26 +/- 20 months. RESULTS: The systolic gradient
      across the coarcted segment decreased from 59 +/- 18 mmHg to 10 +/- 11 mmHg
      following BCA (p < 0.001). The procedure was successful in 82% of patients, and
      partial improvement was obtained in 17%. Repeat intervention was performed in 13%
      of the follow-up group. Surgical intervention was needed in 8 patients.
      CONCLUSION: Balloon angioplasty is an effective first-line intervention in
      patients with native coarctation of the aorta.

PMID- 10953104
TI  - Balloon angioplasty of native coarctation of the aorta.

PMID- 10953105
TI  - Multi-vessel coronary stenting--procedural results and late clinical outcomes: a
      comparison with single-vessel stenting.
AB  - The purpose of this study was to assess the 1-year clinical outcome of patients
      with multi-vessel coronary artery disease (CAD) who underwent coronary stenting,
      and to compare the results with single-vessel coronary stenting carried out
      during the same period. We evaluated the in-hospital and 12-month clinical
      outcomes [death, Q-wave myocardial infarction (MI) and repeat revascularization
      rates at one year] in 384 consecutive patients treated with coronary stents in 2
      (92% of patients) or 3 of the native coronary arteries and compared the outcome
      to 624 consecutive patients undergoing stenting in a single coronary artery
      between January 1, 1997 and January 31, 1999. The overall procedural success was
      obtained in 99% of patients with 2- or 3-vessel stenting and 98% of patients with
      single-vessel stenting. Procedural complications were similar (2.9% vs 2.6%; p =
      0.12). During follow-up, target lesion revascularization was 16% in multi-vessel
      and 14% in single-vessel stenting (p = 0.38) and repeat revascularization was
      also similar for both groups (19% vs. 20%; p = 0.73). There was no difference in
      death (0.8% vs. 1.3%; p = 0.31) and Q-wave MI (0.7% vs. 1.4%; p = 0. 16) in the 2
      groups. Overall cardiac event-free survival was similar for both groups (76% vs.
      78%; p = 0.54). Multi-vessel stenting in carefully selected patients in our
      experience had a high procedural success with very low complication rates. The
      one-year clinical outcomes were acceptable and were similar to the results of
      single-vessel stenting.

PMID- 10953106
TI  - European high-activity (32)P radioactive stent experience.
AB  - Brachytherapy by implantation of a radioactive stent is an alternative approach
      to catheter-based systems to reduce restenosis. The pilot clinical trials using
      32P radioactive b-emitting stents at low-to-intermediate activity (0.5Eth 3.0
      mCi) showed that restenosis at 6 months was not different from that of currently
      available non-radioactive stents. The evaluation of the efficacy in reducing
      restenosis of radioactive stents with higher activities (3Eth 24 mCi) started in
      Europe (Milan, Rotterdam and Vienna) between 1998 and 1999. In the Milan and
      Rotterdam experience, 32P radioactive stents with an activity of 3Eth 12 mCi
      demonstrated a reduction of intra-stent restenosis to < 4%. However, a high-edge
      restenosis > 30% was observed in the first 1Eth 3 mm outside the stent margins.
      This edge effect might be due to a low dose of radiation at the stent margins
      combined with systematic balloon injury in the reference segments. The hypothesis
      that a further increase in stent activity (12Eth 21 mCi) associated with a
      reduced balloon injury outside the stent could solve the problem of edge
      restenosis was not confirmed by the Milan experience; edge restenosis still
      occurred in 26% of the lesions treated by a single 32P radioactive stent, even if
      a nonaggressive stent implantation strategy was used. Two approaches under
      investigation to solve the problem of edge restenosis are: 1) lengthening the
      stent with a non-radioactive stent (cold-ends stent) to prevent negative
      remodeling; and 2) extending the area of irradiation beyond the balloon-injured
      area by an increased activity at the stent ends (hot-ends stent).

PMID- 10953107
TI  - Arrhythmogenic right ventricular dysplasia and the implantable cardioverter
      defibrillator: a case report and review of the literature.

PMID- 10953108
TI  - A novel approach for crossing a virtually occluded vessel using ultra-low-profile
      balloon backup.
AB  - We discuss a case in which a novel ultra-low-profile angioplasty balloon was used
      to provide wire backup by advancing the uninflated balloon nose into the entry
      point of a virtually occluded lesion. This enabled crossing of the lesion, and
      demonstrates how an improved balloon design can directly lead to improved
      clinical outcomes.

PMID- 10953109
TI  - A rare, unreported complication during coronary rotational atherectomy.
AB  - We describe a rare and unreported complication during rotational atherectomy of a
      heavily calcified lesion in the left circumflex artery in a 79-year-old man. The
      Teflon sheath housing the drive shaft fractured, most probably due to
      overtightening of the Y-adapter hemostatic valve. As a result, there was intense
      spasm leading to acute ischemia and the procedure had to be abandoned. This case
      highlights the importance of using familiar and thoroughly tested hardware in
      technique-intensive procedures.

PMID- 10953110
TI  - Myocardial bridging of left circumflex coronary artery associated with acute
      myocardial infarction.
AB  - Myocardial bridging of coronary arteries has been associated with myocardial
      infarction (MI), conduction disturbances, and sudden cardiac death. There are
      several reports on MI in association with myocardial bridging of the left
      anterior descending coronary artery. Here we present a case report of acute MI
      associated with myocardial bridging of the left circumflex coronary artery.

PMID- 10953111
TI  - Rupture of the right sinus of valsalva into the right ventricle:
      echocardiographic and angiographic imaging.
AB  - We report a 16-year-old girl with acute rupture of the sinus of Valsalva. This
      case is unique in that the right coronary sinus of Valsalva ruptured into both
      the right and left ventricles, producing severe aortic insufficiency. The
      diagnosis was made with two-dimensional and color Doppler echocardiography which
      showed an abnormal jet flow from the aortic root into both ventricles. The
      diagnosis was confirmed by magnetic resonance imaging and aortic root
      angiography. Early diagnosis is important so that urgent surgical treatment can
      be taken.

PMID- 10953112
TI  - The current status of bladder preservation in the treatment of muscle invasive
      bladder cancer.
AB  - PURPOSE: Bladder preserving strategies for muscle invasive bladder cancer have
      evolved from single modality to multimodality treatment approaches with improved
      results. MATERIALS AND METHODS: We review the rationale for a multimodality
      approach to treat invasive bladder cancer and the results of some recent
      multimodality bladder sparing treatments. In addition, we compare this approach
      to radical cystectomy. RESULTS: Multimodality bladder sparing treatment involves
      combined transurethral bladder resection, external beam radiation with concurrent
      radiosensitizers and cisplatin based chemotherapy. With this approach overall 5
      year survival is 48% to 63% and overall 5-year survival with the bladder intact
      is 36% to 43%. Survival with this approach is comparable to that in series of
      patients treated with primary radical cystectomy. The primary impetus for a
      multimodality bladder sparing approach is the improved quality of life associated
      with retaining the native bladder. However, the multimodality bladder sparing
      approach involves a complex treatment schedule associated with significant
      morbidity and mortality. Cystectomy is eventually required after attempted
      bladder preservation in 34% to 45% of cases and the rate of superficial
      recurrence is approximately 28%. CONCLUSIONS: Multimodality bladder sparing
      treatment is a viable option at centers with a dedicated multidisciplinary team.
      However, primary radical surgery remains the standard of care for invasive
      bladder cancer.

PMID- 10953113
TI  - Tribute to William W. Scott.

PMID- 10953115
TI  - Reassessing the efficacy of the Dornier MFL-5000 lithotriptor.
AB  - PURPOSE: The Dornier MFL-5000* is a multifunctional lithotriptor unit that has
      been purported to be highly efficacious for treating stones. Our experience led
      us to believe that the actual success rates are not as high as those reported by
      others. We objectively reexamined the efficacy of this device and factors
      contributing to treatment success or failure. MATERIALS AND METHODS: We
      retrospectively reviewed the records and x-rays of 105 consecutive patients
      treated with extracorporeal shock wave lithotripsy (ESWL*) using the MFL-5000
      during an 18-month period from September 1997 to March 1999. One patient was
      excluded from study due to a stone within a caliceal diverticulum. Patients were
      divided evenly by gender and stone laterality. In 70% of cases a stent was placed
      preoperatively to relieve obstruction and/or facilitate the passage of calculous
      fragments. The majority of stones (70%) were 10 mm. or less. Treatment success
      was determined by examining x-rays done preoperatively and at a median of 4 weeks
      postoperatively. RESULTS: ESWL was successful in only 47% of our patients,
      defined as residual stone fragments 2 mm. or less. A secondary procedure was
      required in 27% of the patients, including repeat ESWL in 6, ureteroscopic stone
      manipulation in 14, percutaneous tube placement in 1 and percutaneous
      nephrolithotripsy in 7. Factors contributing to secondary procedures and poor
      stone clearance were a stone burden of greater than 100 mm.2 and mid pole
      location (p = 0.0242 and 0.016, respectively). Poor stone fragmentation and
      clearance were noted despite significantly more shocks delivered (p = 0.0122).
      Only a small stone burden of 50 mm.2 or less responded well to ESWL (p = 0.
      0142). CONCLUSIONS: These results compel us to reconsider the effectiveness of
      the Dornier MFL-5000 lithotriptor. We encourage groups at other institutions to
      reexamine and report their success rates. We recommend the use of this
      lithotriptor only for a stone burden of 50 mm.2 or less.

PMID- 10953114
TI  - Clinical usefulness of the novel marker BLCA-4 for the detection of bladder
      cancer.
AB  - PURPOSE: Previous studies at our laboratory identified 6 bladder cancer specific
      nuclear matrix proteins termed BLCA-1 to 6. We recently developed an immunoassay
      that detects the bladder cancer specific nuclear matrix protein BLCA-4. We
      analyzed urine samples from patients with bladder cancer, those with spinal cord
      injury and normal volunteers to determine the BLCA-4 level in these 3 groups.
      MATERIALS AND METHODS: Urine samples obtained from 51 normal controls, and 54
      patients with bladder cancer and 202 with spinal cord injury were tested for BLCA
      4. We evaluated the association of BLCA-4 level with tumor grade and stage, urine
      cytology and bladder cancer history in the nonspinal cord injured population.
      Similarly we compared parameters associated with BLCA-4, such as spinal cord
      injury duration, catheterization, history of urinary tract infection, smoking and
      urine culture, in spinal cord injured patients. RESULTS: We established a normal
      cutoff point of 13 optical density units per microg. protein for the BLCA-4
      assay. The BLCA-4 level was less than the cutoff in all 51 normal controls, while
      in 53 of the 55 urine samples (96.4%) of patients with bladder cancer and 38 of
      the 202 (19%) of spinal cord injured patients urinary BLCA-4 was greater than the
      cutoff. There was no correlation of any individual factors studied in these
      cases, including urinary tract infection and urinary BLCA-4. CONCLUSIONS:
      Elevated urinary BLCA-4 levels may accurately identify bladder cancer and
      distinguish these patients from normal individuals. There is no correlation of
      urinary BLCA-4 with a history of urinary tract infection, smoking,
      catheterization or cystitis considered independently. Urinary BLCA-4
      determination appears to have high potential as a test for screening and
      monitoring bladder cancer in the general population and in groups at high risk
      for the disease, such as those with spinal cord injury.

PMID- 10953116
TI  - The efficacy and safety of synchronous bilateral extracorporeal shock wave
      lithotripsy.
AB  - PURPOSE: Bilateral renal calculi have traditionally been managed by staged
      extracorporeal shock wave lithotripsy (ESWLdagger) due to concern about bilateral
      obstruction. We evaluated the safety and efficacy of synchronous bilateral ESWL
      in a large series of patients treated at our institution to determine the safety
      and efficacy of this controversial technique in what is to our knowledge the
      largest series to date. MATERIALS AND METHODS: We retrospectively evaluated the
      records of 120 patients with a mean age of 48 years who underwent bilateral
      synchronous ESWL between 1987 and 1996. Of the patients 71 (59%) were male.
      Average followup was 21 months. ESWL was performed using a Dornier HM3
      lithotriptor in all cases. Intraoperative technique and postoperative factors
      were analyzed using the Pearson product moment correlation, the 2-tailed t test
      and multiple regression analysis. RESULTS: Mean stone size was 13 and 15 mm. on
      the left and right sides, respectively. There was an average of 1.7 stones per
      renal unit. After 1 treatment 72 of the 120 patients (60%) were stone-free
      bilaterally, while 72% and 73% of left and right renal units, respectively, were
      also stone-free. Mean creatinine was similar preoperatively and postoperatively
      (1.46 and 1.41 mg./dl., respectively, p = 0.73). There was 1 or more
      complications in 18 cases. The majority of complications were minor with no long
      term morbidity or death and there was no case of bilateral obstruction or renal
      failure. Additional procedures were required in 19 patients (16%) due to
      significant residual stone disease or obstruction during followup. Multiple
      regression analysis revealed that only patient age, a right ureteral stent and
      the number of shocks correlated with the complication rate. Stone size and number
      independently increased the probability of treatment failure and a repeat
      procedure (p <0.05). Patients with stones 20 mm. or greater were at particularly
      high risk for treatment failure and additional procedures. A total of 27 of the
      35 patients (77%) with residual calculi and 13 of the 19 (68%) requiring
      additional procedures were in this high risk subgroup. CONCLUSIONS: Bilateral
      synchronous ESWL is safe and effective monotherapy for bilateral urolithiasis. No
      patient had bilateral obstruction or renal failure and no deterioration of renal
      function was detected at followup. Knowing which patient populations are at
      higher risk for failure or complications may guide decision making.

PMID- 10953117
TI  - Current management of severely encrusted ureteral stents with a large associated
      stone burden.
AB  - PURPOSE: We review our recent experience with encrusted retained ureteral stents
      associated with a large stone burden as well as current endoscopic options
      available for management. MATERIALS AND METHODS: One man and 3 women presented to
      our department between May 1998 and April 1999 for treatment of an encrusted
      retained ureteral stent. One patient had a history of 3 episodes of ureteral
      stent encrustation during the last 6 years. We reviewed the management of these
      stents and the associated stone burden. RESULTS: Average patient age was 32.5
      years (range 25 to 41). Average interval that the encrusted stent remained in
      place was 7 months (range 3 to 12). In the 3 women pregnancy was associated with
      the retained stent. All patients required 2 to 6 endourological approaches
      (average 4.2) performed at 1 or multiple sessions to render them stone-free and
      stent-free. Postoperatively sepsis in 1 case necessitated a prolonged intensive
      care unit stay with eventual recovery. CONCLUSIONS: Successful management of a
      retained encrusted stent requires combined endourological approaches.
      Percutaneous nephrostolithotomy and ureteroscopy are often necessary for treating
      a severely encrusted stent and the associated stone burden.

PMID- 10953118
TI  - What to do with all the tools? Is less more or more less?

PMID- 10953119
TI  - Ureteropelvic junction obstruction: long-term followup of adults with and without
      surgical treatment.
AB  - PURPOSE: We compared the long-term outcome of hydronephrosis due to pyeloureteral
      obstruction based on excretory urography findings and renal function in patients
      who did and did not undergo pyeloplasty. MATERIALS AND METHODS: We followed 83
      adults for a mean of 17 years after the diagnosis of hydronephrosis. The choice
      of conservative or surgical management was based on the results of excretory
      urography, pelvic manometry, fluoroscopy of pelvic and ureteral peristalsis,
      isotope renography and renal clearance studies but symptom severity was
      considered greatly important. Three patients not included in the study underwent
      primary nephrectomy due to poor ipsilateral function, while 47 underwent
      pyeloplasty and 36 no surgery. RESULTS: Nephrectomy was later performed in 2
      patients each in the pyeloplasty and no surgery group, respectively, because of
      pyelonephritis and stone formation in 3 and persistent pain in 1. Hypertension
      developed in 2 cases in each group. Renal pelvic size was considerably decreased
      after pyeloplasty and dilatation increased in only a few kidneys in the
      nonsurgical group. Excluding the 4 patients treated with late nephrectomy serum
      creatinine pathologically increased in only 1 who was treated conservatively.
      Split function improved from 40.8% to 47.1% of total function after pyeloplasty
      but the total glomerular filtration rate did not improve significantly.
      CONCLUSIONS: In the absence of infection and stone formation hydronephrosis in
      adults seems to be a fairly benign condition and followup should be directed
      mainly toward detecting these complications. Recurrent flank pain still seems to
      be the best indication of the need for surgery.

PMID- 10953120
TI  - Evaluation of the urological complications of living related renal
      transplantation at a single center during the last 10 years: impact of the Double
      J* stent.
AB  - PURPOSE: We evaluated the impact of the routine use of Double-J stents for
      decreasing urological complications in living related renal transplantation at a
      single center during the last 10 years. MATERIALS AND METHODS: Our 3-phase
      longitudinal study included 670 consecutive living related renal transplants from
      1989 to 1998. In phase 1 from 1989 to 1993 a stent was introduced as and when
      required in only 15 of 170 patients. In phase 2 from January 1994 to April 1995
      we randomized 57 and 43 cases to stenting and no stenting, respectively. The
      stent was removed after 4 weeks. In phase 3 from May 1995 to December 1998 all
      patients received a stent, which was removed 10 to 14 days just before discharge
      home. We reviewed urological complications at various time frames to determine
      the impact of routine Double-J stenting on decreasing urological complications.
      RESULTS: In phase 1 the major ureteral complication rate was 8.8%, which
      decreased to 3% in phase 2 when half of our cases were stented. In phase 3 there
      was only 1 ureteral complication (0.04%) in 400 patients, of whom all received a
      stent. The overall ureteral complication rate in nonstented and stented cases was
      8.5% (18 of 213) and 0.22% (1 of 457). There was no difference in urological
      complications or stent related problems whether the stent was removed at 4 or 2
      weeks. However, stent removal at 2 weeks eliminated the possibility of a
      forgotten stent, avoided repeat hospitalization for stent removal and decreased
      the cost. Routine stenting was cost-effective and almost eliminated urological
      complications. CONCLUSIONS: Routine Double-J stenting prevents ureteral
      complications. Early removal at 2 weeks is advisable. The short duration of
      stenting is effective and saves the cost of repeat hospitalization at a later
      date.

PMID- 10953121
TI  - Bilateral nephrectomy with concomitant renal graft transplantation for autosomal
      dominant polycystic kidney disease.
AB  - PURPOSE: There has been controversy about pre-transplant nephrectomy in patients
      with autosomal dominant polycystic kidney disease. Kidneys may be removed in
      these patients when they cause respiratory compromise, early satiety, increased
      abdominal girth, pain, hematuria or recurrent infection. We determined whether
      concomitant bilateral nephrectomy at renal transplantation is safe and
      efficacious. MATERIALS AND METHODS: Between December 1996 and January 1999, 10
      patients with autosomal dominant polycystic kidney disease underwent bilateral
      nephrectomy with concomitant renal grafting (group 1). We compared these patients
      to 9 with autosomal dominant polycystic kidney disease matched for age and gender
      who underwent transplantation only (group 2) and 4 with the same condition who
      underwent bilateral nephrectomy and renal transplantation as staged procedures
      (group 3). RESULTS: No patients died perioperatively. There was a lower rate of
      complications in group 1 than in groups 2 or 3. The only significant differences
      in intraoperative and perioperative parameters were operative time and
      intraoperative blood loss, which were greater in group 1 than in group 2. We
      noted no significant differences in groups 1 and 3. Patient satisfaction analyzed
      by a survey revealed that the 70% of group 1 patients who responded were
      satisfied with kidney removal and 7 of the 9 in group 2 desired native kidney
      removal. All group 3 patients already had a functioning renal graft but were
      satisfied with native kidney removal, although they would rather have undergone
      bilateral nephrectomy at transplantation. CONCLUSIONS: Our data imply that there
      is no higher morbidity or mortality when performing concomitant bilateral
      nephrectomy at renal transplantation in patients with renal failure due to
      autosomal dominant polycystic kidney disease. There was a higher rate of
      satisfaction in patients who underwent nephrectomy and transplantation
      simultaneously, while those who did not undergo concomitant procedures strongly
      desired to have had that option. Bilateral nephrectomy may alleviate symptoms
      while providing greater room for renal graft placement. When done without
      transplantation, bilateral nephrectomy resulted in the highest number of
      complications. Our data indicate that if bilateral nephrectomy is performed as an
      adjunct to transplantation, it should be done at renal grafting.

PMID- 10953122
TI  - The use of liver transplant techniques to aid in the surgical management of
      urological tumors.
AB  - PURPOSE: Inferior vena cava tumor thrombus complicates radical nephrectomy.
      Various approaches have been used to deal with this problem, including venovenous
      and cardiopulmonary bypass. Applying organ transplant techniques enhances the
      exposure of urological tumors and may avoid bypass. MATERIALS AND METHODS: A
      total of 26 patients underwent surgery by techniques developed to facilitate
      orthotopic liver transplantation. Of the patients 15 with renal cell carcinoma
      and an intracaval tumor thrombus underwent piggyback style mobilization of the
      liver off of the retrohepatic inferior vena cava to allow enhanced access and
      vascular control, while 11 underwent conventional mobilization of the liver and
      retrohepatic inferior vena cava en bloc to allow enhanced access to various
      renal, adrenal and retroperitoneal tumors. RESULTS: In the 11 patients surgery
      was successful with a median blood loss of 200 ml. Postoperative ileus in 1 case
      was the only complication. We resected 5 infrahepatic thrombi without
      complications and with a median blood loss of 500 ml. In 7 patients with a
      retrohepatic inferior vena caval thrombus median blood loss was 1,500 ml.,
      including 1 who died postoperatively, presumably due to a massive pulmonary
      embolus. Caval atrial tumor thrombus in 3 cases was successfully removed via a
      completely abdominal approach and sternotomy in 2. Cardiopulmonary bypass with
      hypothermic circulatory arrest was required in 1 of these cases. CONCLUSIONS:
      Liver mobilization was helpful for managing difficult urological tumors. Patients
      with a retrohepatic or even suprahepatic inferior vena caval thrombus may be
      treated without sternotomy or thoracotomy and cardiopulmonary bypass.

PMID- 10953123
TI  - Serum immunosuppressive acidic protein and natural killer cell activity in
      patients with metastatic renal cell carcinoma before and after nephrectomy.
AB  - PURPOSE: To our knowledge the impact of nephrectomy on stage M1 renal cell
      carcinoma remains to be determined. We previously reported that nephrectomy is
      beneficial in patients with elevated serum C-reactive protein before treatment,
      and those in whom nadir C-reactive protein decreases postoperatively to within
      the normal range may expect longer survival when surgery is combined with
      postoperative immunotherapy. In this study we determine the effect of nephrectomy
      on the immune response in patients with metastatic renal cell carcinoma.
      MATERIALS AND METHODS: We retrospectively reviewed the records of 40 patients
      with metastatic renal cell carcinoma diagnosed at our institution between 1986
      and 1999. These patients underwent nephrectomy before cytokine therapy with
      interferon. Before and after nephrectomy we measured serum C-reactive protein,
      serum immunosuppressive acidic protein and peripheral blood natural killer cell
      activity. RESULTS: In 15 patients with pretreatment serum C-reactive protein
      within the normal range (less than 1 ng./ml.) there was no significant difference
      before and after nephrectomy in the serum immunosuppressive acidic protein level
      or natural killer cell activity (p = 0.4587 and 0.3892, respectively). On the
      other hand, in 25 patients with serum C-reactive protein elevated before
      treatment to 1 ng./ml. or greater serum immunosuppressive acidic protein
      decreased significantly and natural killer cell activity increased significantly
      after cytoreductive surgery (p = 0.0002 and 0.0286, respectively). CONCLUSIONS:
      Our study implies that nephrectomy may be beneficial in patients with elevated
      serum C-reactive protein before treatment. Further evaluation by a prospective
      study is needed to make a definitive conclusion.

PMID- 10953124
TI  - Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a
      randomized placebo controlled study.
AB  - PURPOSE: Present therapeutic approaches to control hypersensitive disorder of the
      lower urinary tract and bladder pain are clinically and scientifically
      unsatisfactory. We performed a randomized placebo controlled study with followup
      after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive
      disorder and bladder pain. MATERIALS AND METHODS: We prospectively randomized 18
      patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin
      intravesically (group 1) or a placebo saline solution only (group 2). All
      patients had at least a 6-month history of frequency, nocturia, urgency and
      symptoms of pelvic pain as well as no urinary tract infection within the last 3
      months, functional disorders of the lower urinary tract, or other vesical or
      urethral pathology. Pretreatment voiding pattern and pain score were recorded.
      Patients were evaluated after 30 days (primary end point) and 3 months (secondary
      end point). RESULTS: The 2 groups were adequately homogeneous in regard to
      patient age, sex ratio, disease duration, voiding pattern and pain score. At the
      primary end point mean frequency plus or minus standard error of mean was
      decreased from 12. 444 +/- 0.70 voids to 7.111 +/- 0.67 and nocturia from 3.777
      +/- 0. 27 to 1.666 +/- 0.16 (p <0.01). We observed a lesser significant
      improvement in mean frequency in group 1 at the secondary end point to 10.444 +/-
      0.94 voids (p <0.05). No significant modification was noted in patients assigned
      to placebo. Mean pain score significantly decreased in group 1 at the primary end
      point from 5.555 +/- 0.29 to 2.666 +/- 0.23 (p <0.01) but not at the secondary
      end point (4.777 +/- 0.66, p >0.05). No statistically significant improvement in
      mean pain score was observed in placebo group 2. During resiniferatoxin infusion
      4 group 1 patients noticed a light warm or burning sensation at the suprapubic
      and/or urethral level. CONCLUSIONS: Intravesical resiniferatoxin may
      significantly improve the voiding pattern and pain score in patients with
      hypersensitive disorder and bladder pain. Because resiniferatoxin did not cause a
      significant warm or burning sensation at the suprapubic and/or urethral level, it
      may be considered a new strategy for treating hypersensitive disorder and bladder
      pain. However, further studies are necessary to confirm our results and define
      the resiniferatoxin mechanism of action, dose and necessary treatment schedule.

PMID- 10953125
TI  - The 3-month clinical response to intravesical therapy as a predictive factor for
      progression in patients with high risk superficial bladder cancer.
AB  - PURPOSE: We analyzed the 3-month clinical response to intravesical therapy as a
      factor predictive of progression in patients with high risk superficial bladder
      cancer. MATERIAL AND METHODS: We evaluated 191 patients with high risk
      superficial bladder cancer, 111 with secondary or associated bladder carcinoma in
      situ and 80 with stage T1 grade 3 disease who were treated with intravesical
      therapy. We considered only clinically complete and no responses at the 3-month
      endoscopic study. To determine the predictive value of the 3-month clinical
      response we differentiated progression into superficial and invasive types.
      RESULTS: At a median followup of 73 months 91 patients (47.6%) had progression,
      which was superficial in 48 (25. 1%) and invasive in 43 (22.5%). Invasive
      progression was associated with significantly higher cause specific mortality
      than superficial progression (p = 0). In the latter cases cause specific
      mortality was higher than in those without progression (p = 0.001). Although
      cystectomy significantly decreased the cause specific mortality rate in patients
      with invasive progression (p = 0.0001), this rate was high at 46.3%. Univariate
      and multivariate analyses revealed that the 3-month clinical response was a
      significant predictive factor for progression. Moreover, stratifying this
      variable showed that this response was the only independent factor predictive of
      invasive progression in cases of no response with stage T1 grade 3 tumor, bladder
      carcinoma in situ, or prostate mucosa or duct involvement (p = 0). In our series
      41 patients (21.5%) did not respond after intravesical therapy at the 3-month
      evaluation, including 29 with stage T1 grade 3 disease, bladder carcinoma in
      situ, or prostate mucosa or duct involvement. Progression in 24 of these 29
      patients (82.3%) was classified as invasive in 21 (73.6%). CONCLUSIONS: Invasive
      progression threatens the cause specific survival of patients with high risk
      superficial bladder cancer even when cystectomy is performed. The 3-month
      clinical response was an excellent predictive factor for invasive progression.
      Early cystectomy should be considered when stage T1 grade 3 tumor, bladder
      carcinoma in situ, or prostate mucosa or duct involvement is present at the 3
      month clinical evaluation.

PMID- 10953126
TI  - The challenge of improved diagnostic and prognostic indicators of superficial
      bladder cancer.

PMID- 10953127
TI  - Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured
      patients: a new alternative to anticholinergic drugs? Preliminary results.
AB  - PURPOSE: We evaluated the efficacy of botulinum-A toxin injections into the
      detrusor muscle in patients with spinal cord injury, detrusor hyperreflexia and
      urge incontinence resistant to anticholinergic drugs. The purpose of treatment
      was to suppress incontinence episodes and increase functional bladder capacity.
      MATERIALS AND METHODS: Included in our prospective nonrandomized study done at 2
      clinics were 31 patients with traumatic spinal cord injury who emptied the
      bladder by intermittent self-catheterization. These patients had severe detrusor
      hyperreflexia and incontinence despite a high dose of anticholinergic medication.
      Pretreatment evaluation included a clinical examination and complete urodynamic
      investigation. Under cystoscopic control a total of 200 to 300 units of botulinum
      A toxin were injected into the detrusor muscle at 20 to 30 sites (10 units per
      ml. per site), sparing the trigone. Clinical and urodynamic followup was planned
      for 6, 16 and 36 weeks after treatment. Patients were asked to decrease their
      intake of anticholinergic drugs during week 1 after treatment. RESULTS: Of the 21
      patients 19 underwent a complete examination 6 weeks after the botulinum-A toxin
      injections, and 11 at 16 and 36 weeks. At the 6-week followup complete continence
      was restored in 17 of 19 cases in which anticholinergic medication was markedly
      decreased or withdrawn. Less satisfactory results in 2 cases were associated with
      an insufficient dose of 200 units botulinum-A toxin. After the injections overall
      mean reflex volume and mean maximum cystometric bladder capacity plus or minus
      standard deviation significantly increased from 215.8 +/- 90.4 ml. to 415.7 +/-
      211.1 (p <0.016) and 296.3 +/- 145.2 to 480.5 +/- 134.1 (p <0.016), respectively.
      There was also a significant decrease after treatment in mean maximum detrusor
      voiding pressure from 65.6 +/- 29.2 cm. water to 35 +/- 32. 1 (p <0.016). Mean
      post-void residual urine volume catheterized at the end of the urodynamic
      examination increased significantly from a mean of 261.8 +/- 241.3 ml. to 490.5
      +/- 204.8 (p <0.016). Moreover, autonomic dysreflexia associated with bladder
      emptying that manifested as a hypertensive crisis during voiding disappeared
      after treatment in the 3 patients with tetraplegia. Satisfaction was high in all
      successfully treated patients and no side effects were observed. Ongoing
      improvement in urodynamic parameters and incontinence was already present in all
      patients reevaluated at 16 and 36 weeks. CONCLUSIONS: Botulinum-A toxin
      injections into the detrusor seem to be a safe and valuable therapeutic option in
      spinal cord injured patients with incontinence resistant to anticholinergic
      medication who perform clean intermittent self-catheterization. Successfully
      treated patients become continent again and may withdraw from or markedly
      decrease anticholinergic drug intake. A dose of 300 units botulinum-A toxin seems
      to be needed to counteract an overactive detrusor. The duration of bladder
      paresis induced by the toxin is at least 9 months, when repeat injections are
      required.

PMID- 10953128
TI  - Noninvasive outcome measures of urinary incontinence and lower urinary tract
      symptoms: a multicenter study of micturition diary and pad tests.
AB  - PURPOSE: We assessed the test-retest reliability of a 24, 48 and 72-hour
      micturition diary and pad test in patients referred for the evaluation of urinary
      incontinence and lower urinary tract symptoms. MATERIALS AND METHODS: We
      prospectively enrolled 109 patients referred for the evaluation of lower urinary
      tract symptoms in our multicenter study. Patients were requested to complete a 72
      hour micturition diary and pad test, and repeat each test during a 1-week
      interval. The test-retest reliability of various parameters of the 72-hour
      micturition diary and pad test was analyzed and compared. Further analysis was
      done to compare the test-retest reliability of 24, 48 and 72-hour studies
      performed on the same days after a 1-week interval. Reliability was assessed by
      Lin's concordance correlation coefficient (CCC) with a cutoff value of 0.7
      indicating test-retest reliability. RESULTS: Of the 109 patients 106 (97%) with a
      median age of 64 years completed the study. The number of pads and total weight
      gain appeared to be reliable measures of the 24, 48 and 72-hour pad tests. For
      the 24-hour diary the total number of incontinence episodes was a reliable
      measure, while the total number of voiding episodes was marginally reliable (mean
      CCC 0.785 and 0. 689, respectively). For the 48-hour diary the number of
      incontinence episodes and total number of voiding episodes were reliable measures
      (mean CCC 0.78 and 0.83, respectively), while for the 72-hour diary each
      parameter was highly reliable (CCC 0.86 and 0.826, respectively). However, an
      increased test period was associated with decreased patient compliance.
      CONCLUSIONS: The 24-hour pad test and micturition diary are reliable instruments
      for assessing the degree of urinary loss and number of incontinent episodes,
      respectively. Increasing test duration to 48 and 72 hours increases reliability
      but is associated with decreased patient compliance.

PMID- 10953129
TI  - The long-term outcome of artificial urinary sphincters.
AB  - PURPOSE: We reviewed the outcome of artificial urinary sphincters inserted more
      than 10 years ago. MATERIALS AND METHODS: We analyzed the records of 100 patients
      and mailed a questionnaire to those without recent followup. RESULTS: Overall 84
      patients were continent, including 36 with the original artificial urinary
      sphincter in place who were dry at a median followup of 11 years and 27 in whom
      the device was successfully replaced due to mechanical failure who were
      previously continent for a median of 7 years. In 21 patients it was removed due
      to infection or erosion and reimplantation was successful 3 to 6 months later or
      they remained dry without another artificial urinary sphincter. Of the male
      patients with a bulbar and bladder neck sphincter 92% and 84%, respectively, were
      continent at 10 years as well as 73% of the females. Device survival was 66% at
      10 years. Overall 37% of the prostheses were removed due to infection or erosion
      in the 10-year period with the highest risk in females (56%) and lowest in males
      with a bulbar sphincter (23%). CONCLUSIONS: The artificial urinary sphincter is
      effective long-term treatment for incontinence in male patients. In female
      patients the risk of erosion is high, although overall long-term continence is
      satisfactory.

PMID- 10953130
TI  - Switching from intracavernous prostaglandin E1 injections to oral sildenafil
      citrate in patients with erectile dysfunction: results of a multicenter European
      study. The Sildenafil Multicenter Study Group.
AB  - PURPOSE: Intracavernous injection is a well established medical therapy for
      erectile dysfunction. We assessed the rate of success when patients with erectile
      dysfunction who were effectively treated with intracavernous injections of
      prostaglandin E1 were changed to oral therapy with sildenafil citrate. MATERIALS
      AND METHODS: Only patients effectively managing erectile dysfunction by the
      intracavernous injection of 20 microg. or less prostaglandin E1 for more than 6
      months were eligible for study enrollment. After a 4-week run-in phase while
      intracavernous prostaglandin E1 therapy continued and a 48-hour washout period
      176 patients with erectile dysfunction received open label sildenafil orally for
      12 weeks. Satisfaction with treatment was evaluated by the 11-item erectile
      dysfunction index of treatment satisfaction questionnaire. A successful change to
      sildenafil was prospectively defined as a questionnaire score of 0 to 100 after
      sildenafil that was greater than or equal to the score after intracavernous
      prostaglandin E1. RESULTS: Of the 176 patients 69% (95% confidence limit 62 to
      76) successfully changed from intracavernous prostaglandin E1 injections to oral
      sildenafil and elected to continue oral treatment. Mean satisfaction score after
      sildenafil and prostaglandin E1 was 73.8 and 63.9, respectively (p <0.001). Only
      3 patients (1.7%) discontinued therapy because of treatment related adverse
      events. CONCLUSIONS: More than two-thirds of the men with erectile dysfunction
      who were stable on intracavernous injections of 20 microg. or less prostaglandin
      E1 successfully changed to oral sildenafil, as determined by maintained or
      enhanced treatment satisfaction.

PMID- 10953131
TI  - Sperm motility from the vas deferens of spinal cord injured men is higher than
      from the ejaculate.
AB  - PURPOSE: Recent evidence suggests that the seminal plasma of spinal cord injured
      men contributes to their distinctive semen profile of normal sperm concentration
      but low sperm motility and viability. This finding indicates that sperm in these
      men may be normal before exposure to the seminal and prostatic fluids. To
      investigate this question we compared vas aspirated to ejaculated sperm in 12 men
      with spinal cord injury and 14 healthy, age matched controls. MATERIALS AND
      METHODS: Ejaculate was collected by penile vibratory stimulation or
      electroejaculation in spinal cord injured men and by masturbation in controls.
      Sperm was aspirated via microsurgery from 1 hemisectioned vas deferens in spinal
      cord injured men and during routine elective vasectomy in controls. Ejaculated
      and aspirated specimens were compared. RESULTS: In men with spinal cord injury
      mean vas aspirated sperm motility and viability plus or minus standard error of
      mean were significantly higher than mean ejaculated sperm motility and viability
      (54.4% +/- 5.0% and 74.1% +/- 5.3% versus 14.1% +/- 2.6% and 26.1% +/- 4.9%,
      respectively). In controls mean vas aspirated sperm motility and viability were
      not significantly different from mean ejaculated sperm motility and viability
      (77.5% +/- 5.2% and 88.9% +/- 2.5% versus 74.3% +/- 5.2% and 85.0% +/- 3.5%,
      respectively). CONCLUSIONS: In spinal cord injured men sperm motility and
      viability were significantly higher before contact with seminal fluids. Although
      aspirated sperm from men with spinal cord injury generally had lower motility and
      viability than that of controls, implying that epididymal or testicular factors
      may also have a part, the greatest decrease was observed in the ejaculate.
      Further study of infertility in these men should focus on prostatic and seminal
      vesicle factors.

PMID- 10953132
TI  - p53 accumulation associated with bcl-2, the proliferation marker MIB-1 and
      survival in patients with prostate cancer subjected to watchful waiting.
AB  - PURPOSE: We describe the association of p53 nuclear protein accumulation with bcl
      2 expression, tumor cell proliferation and clinical outcome in a prostate cancer
      population undergoing watchful waiting. MATERIALS AND METHODS:
      Immunohistochemical staining for p53 was semiquantitatively scored in archival
      formalin fixed, paraffin embedded tumor tissue obtained at diagnosis in 221
      patients with prostate cancer. At a median of 15 years followup was nearly
      complete. Eventually 57% of the patients died of prostate cancer. RESULTS: p53
      Immunohistochemical staining was heterogeneous but in all cases at least clusters
      of tumor cells had nuclear staining for p53. The percent of p53 immunoreactive
      tumor cells was scored as 0 to 4+ in p53 positive hot spots. p53 immunoreactivity
      correlated with clinical stage and histopathological grade (p = 0.003 and 0.009,
      respectively). When dichotomized into low (0% to 50%) and high (51% to 100%)
      immunoreactivity groups of 40 and 181 patients, respectively, p53 accumulation
      was significantly associated with disease specific survival in the study
      population overall (p <0. 0001) and in the 125 with clinically localized disease
      (p = 0.0002). p53 Immunoreactivity was significantly (p <0.001) associated with
      the proliferation marker MIB-1 (median value 10.3, range 0 to 46.1) but
      insignificantly (p = 0.8) correlated with bcl-2 expression (52% positive).
      However, patients with combined favorable MIB-1 and bcl-2 status were stratified
      into significant (p = 0.02) prognostic groups by p53 immunohistochemical status.
      Multivariate analysis revealed that p53 immunoreactivity was a significant
      prognostic factor in patients with clinically localized prostate cancer (p
      <0.0001). CONCLUSIONS: p53 Nuclear protein accumulation detected by
      immunohistochemical study was an independent adverse prognostic factor in
      patients with prostate cancer undergoing watchful waiting.

PMID- 10953133
TI  - Cytokine variations in patients with hormone treated prostate cancer.
AB  - PURPOSE: We evaluated the immunological response in patients with hormone
      sensitive and refractory prostate cancer, and untreated benign prostatic
      hyperplasia (BPH). MATERIALS AND METHODS: Serum levels of pro-inflammatory and
      anti-inflammatory cytokines were measured by enzyme-linked immunosorbent assay in
      3 groups of patients. The groups included 18 men with a mean age of 79 years who
      had hormone sensitive prostate cancer, mean prostate specific antigen (PSA) plus
      or minus standard deviation 1.03 +/- 2.65 ng./ml. and a mean of 35 months of
      treatment, 10 with a mean age of 86 years who had hormone refractory prostate
      cancer, mean PSA 27.52 +/- 42.23 ng./ml. and a mean of 42 months of treatment,
      and 19 with a mean age of 73 years who had BPH and mean PSA 3.37 +/- 2.47 ng./ml.
      Results were compared with those in 10 age matched, disease-free controls. In the
      hormone sensitive group PSA regressed to normal and there was clinical evidence
      of a response to hormone ablation therapy, including orchiectomy, luteinizing
      hormone releasing hormone analogue and androgen blockade. Hormone refractory
      cases had elevated PSA and/or clinical evidence of disease progression. RESULTS:
      Levels of the anti-inflammatory cytokines interleukin (IL)-4, IL-6 and IL-10 were
      significantly elevated in the hormone refractory group compared with values in
      the hormone sensitive group (p = 0.02, 0.01 and 0.0001, respectively). Abnormal
      anti-inflammatory cytokines in hormone resistant cases correlated with elevated
      PSA, while in the BPH group there was no significant difference from controls.
      Pro-inflammatory cytokines in the hormone sensitive and resistant groups were not
      significantly different from those in controls. CONCLUSIONS: Our study indicates
      that in hormone refractory prostate cancer a high level of the anti-inflammatory
      cytokines IL-4, IL-6 and IL-10 develops that is directly associated with elevated
      PSA. Changes in the level of anti-inflammatory cytokines when androgen
      independent cells exist may have an important role in the selection of a subset
      of hormone insensitive cells. These criteria may be used as a prognostic marker
      for the response to hormone ablation therapy in men with prostate cancer.

PMID- 10953134
TI  - Failure to achieve castrate levels of testosterone during luteinizing hormone
      releasing hormone agonist therapy: the case for monitoring serum testosterone and
      a treatment decision algorithm.
AB  - PURPOSE: We report the failure to achieve a castrate level of testosterone
      associated with 3-month depot luteinizing hormone releasing hormone (LH-RH)
      agonist therapy, which to our knowledge is a previously unrecognized outcome.
      MATERIALS AND METHODS: We prospectively enrolled in our study 38 men with
      prostate cancer on 3-month depot LH-RH agonist therapy. We monitored total serum
      testosterone and prostate specific antigen every 28 days beginning 90 days after
      the last depot LH-RH agonist injection. Data were analyzed with castrate
      testosterone defined as less than 50 and 20 ng./dl. or less. RESULTS: Using the
      50 and 20 ng./dl. definitions of castrate testosterone 2 (5%) and 5 (13%) of the
      38 men, respectively, failed to achieve castrate testosterone. A patient with a
      nadir testosterone of 70 ng./dl. subsequently underwent orchiectomy and
      testosterone decreased to 10 ng./dl. thereafter. CONCLUSIONS: A small but
      potentially important subgroup of men on depot LH-RH agonist therapy fail to
      achieve a castrate level of testosterone. Our findings support monitoring
      testicular response when LH-RH agonist therapy is initiated.

PMID- 10953135
TI  - Safety and efficacy of an implantable leuprolide delivery system in patients with
      advanced prostate cancer.
AB  - PURPOSE: We evaluated the pharmacokinetics, safety and efficacy of the
      implantable Viadur++ leuprolide delivery system during 12 months in patients with
      advanced prostate cancer. MATERIALS AND METHODS: Our open label, multicenter,
      dose ranging study was done in 2 phases. The treatment phase was a stratified,
      randomized, parallel evaluation of the safety and efficacy of 1 or 2 implants.
      The safety extension phase assessed the long-term safety and efficacy of 1
      implant. Implant insertion and removal, pharmacokinetic profile and patient
      satisfaction were also evaluated. The primary efficacy parameter was testosterone
      suppression for 12 months but luteinizing hormone and prostate specific antigen
      were also evaluated. RESULTS: Of the 51 patients 27 received 1 and 24 received 2
      implants, of whom 49 completed the 12-month treatment phase. Steady serum
      leuprolide concentration was maintained from day 3 through the remainder of the
      12-month treatment phase and for 2 months after reimplantation. Implantation and
      reimplantation were well tolerated and acceptable to physicians and patients.
      Testosterone suppression to the castrate range was 100% in each group. At 12
      months mean prostate specific antigen decreased from a baseline of approximately
      84% and 91% in groups 1 and 2, respectively. Serious adverse events during the
      study period in 15 patients were not attributable to treatment. CONCLUSIONS: The
      implantable leuprolide delivery system provides effective suppression of
      testosterone in patients with advanced prostate cancer.

PMID- 10953136
TI  - The cost value of medical versus surgical hormonal therapy for metastatic
      prostate cancer.
AB  - PURPOSE: The cost of luteinizing hormone releasing hormone analogue and
      antiandrogen for prostate cancer is being scrutinized by the Health Care Finance
      Administration and other insurers. We compared the discounted present value cost
      of medical hormonal therapy to that of orchiectomy as well as the value created
      by these treatments from the insurer and patient perspectives. MATERIALS AND
      METHODS: We performed a telephone survey of 42 patients receiving hormonal
      therapy to estimate the value created by medical versus surgical castration from
      the patient perspective. The cost of medical hormonal therapy was discounted back
      to the present value and compared with the cost of bilateral orchiectomy.
      RESULTS: The total cost of bilateral orchiectomy was $2,022, while the discounted
      present value cost using the average wholesale price for 30 months of medical
      hormonal therapy was $13,620. Therefore, medical hormonal therapy costs $11,598
      more than orchiectomy ($13,620 - $2,022). A discounted payment of $386 per month
      for 30 months is necessary to recoup the $11,598 difference. All surveyed
      patients on medical hormonal therapy stated that avoiding orchiectomy was worth
      $386 per month and it was an appropriate insurer expense. If patients paid $386
      per month out-of-pocket, 22 of the 42 (52%) would pay the additional monthly
      expense, while 20 (48%) indicated that they could not afford the additional
      expense. CONCLUSIONS: These results indicate that medical hormonal therapy costs
      significantly more than bilateral orchiectomy but creates positive value for men
      with prostate cancer by enabling them to avoid orchiectomy.

PMID- 10953137
TI  - Simultaneous irradiation for prostate cancer: intermediate results with modern
      techniques.
AB  - PURPOSE: In this study of men with early stage prostate cancer we evaluated
      treatment outcome after modern simultaneous irradiation, comprising transperineal
      implantation followed by external beam radiation. Disease-free survival rates
      were calculated according to an undetectable prostate specific antigen (PSA)
      nadir. MATERIALS AND METHODS: From 1992 to 1996, 689 men with clinical stage T1
      T2, N0, Nx prostate cancer were treated with ultrasound guided transperineal
      125iodine seed implantation followed 3 weeks later by external beam radiation.
      Disease-free status was defined as the achievement and maintenance of a PSA nadir
      of 0.2 ng./ml. or less. Median followup was 4 years (range 3 to 7). None of these
      men received neoadjuvant or adjuvant hormonal therapy. RESULTS: Overall 5-year
      disease-free survival was 88%. The 5-year rate according to PSA 4.0 ng./ml. or
      less, 4.1 to 10.0, 10.1 to 20.0 and greater than 20.0 was 94%, 93%, 75% and 69%,
      respectively. Multivariate analysis revealed that pretreatment PSA was the
      strongest indicator of subsequent disease-free status in regard to Gleason score
      or clinical stage. CONCLUSIONS: Intermediate treatment outcome analysis of modern
      simultaneous radiation supports the principles of radiation dose intensification
      for intracapsular disease plus the treatment of potential microscopic capsular
      penetration.

PMID- 10953138
TI  - Prospective assessment of patient reported urinary continence after radical
      prostatectomy.
AB  - PURPOSE: Reported urinary continence rates after radical prostatectomy vary.
      Although modifications of radical prostatectomy meant to improve outcome, such as
      nerve sparing or bladder neck preservation, are in widespread use, to our
      knowledge evidence to support these practices based on patient report is scant.
      We evaluated the potential effects of nerve sparing and bladder neck preservation
      on urinary continence after radical prostatectomy, and assessed the impact of
      various urinary continence definitions on the observed outcome. MATERIALS AND
      METHODS: We prospectively evaluated a cohort of men with prostate cancer who
      elected surgery with and without nerve sparing, and bladder neck preservation as
      primary therapy. A total of 482 men completed a brief urinary continence
      questionnaire preoperatively and postoperatively at a median followup of 18
      months. Urinary continence was followed prospectively using the questionnaire and
      patient reported urinary continence recovery was based on 3 definitions of
      continence. RESULTS: Median time to continence recovery based on patient
      reporting was significantly shorter in the nerve sparing than in the nonnerve
      sparing group when continence was defined as no urinary leakage (5.3 versus 10.9
      months, p <0.01). A multivariate model controlling for baseline factors revealed
      that significant predictors of continence outcome were preoperative continence,
      patient age, nerve sparing and the interaction of nerve sparing with age (p
      <0.05). The definition of urinary continence also affected outcome. CONCLUSIONS:
      The nerve sparing technique of radical prostatectomy was associated with improved
      recovery of urinary continence in an age dependent manner, whereas bladder neck
      preservation was not beneficial. Patient age and the sensitivity of the
      incontinence definitions, as reflected by the associated variable rates of
      preoperative baseline incontinence, are significant contexts for interpreting
      urinary function data after radical prostatectomy. These factors may partially
      explain the variation in continence rates in the literature.

PMID- 10953139
TI  - Characterization and predictors of prostate specific antigen progression rates
      after radical retropubic prostatectomy.
AB  - PURPOSE: Detectable serum prostate specific antigen (PSA) after radical
      prostatectomy indicates recurrent disease and treatment failure. We characterized
      PSA recurrence after prostatectomy and identified predictors of rapid PSA
      progression. MATERIALS AND METHODS: We retrospectively reviewed the medical
      records of 165 patients with detectable PSA after radical prostatectomy to
      characterize the rate of PSA increase and correlate this rate with the possible
      predictors of rapid PSA progression known at prostatectomy. RESULTS: For a median
      of 48 months postoperatively we followed 142 patients with PSA recurrence after
      radical prostatectomy who received no immediate adjuvant therapy. PSA doubling
      time was less than 6, greater than 6, 12, 18 and 24 months in 46%, 54%, 18%, 11%
      and 9% of cases, while time to PSA 50 ng./ml. was greater than 5, 10, 15 and 20
      years in 69%, 34%, 22% and 9%, respectively. Univariate and multivariate analyses
      revealed that rapid PSA doubling time was associated with Gleason secondary
      grade, Gleason score and time to initial detectable PSA (p = 0.019, 0.031 and
      0.0001, and p = 0.043, 0.045 and 0.0001, respectively). CONCLUSIONS: PSA
      recurrence progresses at a greatly variable rate and many recurrences progress
      slowly with a long doubling time. Gleason secondary grade and score appear to be
      predictive of rapid PSA progression. No other pathological features were
      predictive of rapid PSA progression.

PMID- 10953140
TI  - Radical prostatectomy: the value of preoperative, individually labeled apical
      biopsies.
AB  - PURPOSE: Involvement of the prostatic apex with adenocarcinoma is a relatively
      common finding, as is a positive surgical margin at this location. We evaluated
      whether a positive apical core biopsy provides preoperative information that may
      be used as a basis for the subsequent surgical approach in individuals. MATERIALS
      AND METHODS: We evaluated apical prostate cancer in 240 individually labeled,
      preoperative apical core biopsies and the corresponding prostatectomy specimen in
      120 patients who underwent radical prostatectomy for clinically localized
      prostate cancer. Sensitivity, specificity, and positive and negative predictive
      values were calculated for the ability of an individual apical core to predict
      the side of tumor in the surgical specimen using 2 x 2 contingency tables.
      Moreover, univariate subset analysis was done for positive biopsies to assess the
      ability of histopathological characteristics, including Gleason score, cancer
      length, percent of cancer in the core and distance of cancer from the inked
      rectal core end, to predict a positive surgical margin at the apex. RESULTS: The
      positive predictive value of a single positive apical core for identifying tumor
      location correctly in the prostatectomy specimen was 71.1%, while absent cancer
      in the apical biopsy had a negative predictive value of 75.5%. Sensitivity was
      44.5% for a positive biopsy core. In this context the predictive value of an
      individual positive apical core biopsy was only 28.8% for predicting surgical
      margin positivity at the apex. CONCLUSIONS: Cancer and its histopathological
      characteristics in an individual core biopsy failed to predict apical tumor
      involvement as well as a positive apical margin at subsequent radical
      prostatectomy.

PMID- 10953141
TI  - Endorectal magnetic resonance imaging as a predictor of biochemical outcome after
      radical prostatectomy in men with clinically localized prostate cancer.
AB  - PURPOSE: Endorectal magnetic resonance imaging (MRI) of the prostate is sometimes
      performed before radical prostatectomy but to our knowledge its role for
      predicting outcome after radical prostatectomy is not yet established. We
      evaluated the clinical usefulness of endorectal MRI for predicting time to
      prostate specific antigen (PSA) failure after radical prostatectomy in 1,025
      consecutive men with clinically localized or PSA detected prostate cancer. Our
      analysis controlled for PSA level, biopsy Gleason score, clinical T stage and
      percent of positive biopsies. MATERIALS AND METHODS: Using Cox regression
      analysis we prospectively assessed time to PSA failure to determine the role of
      endorectal MRI in predicting PSA outcome after radical prostatectomy at our
      institution, where an expert prostate magnetic resonance radiologist is
      available. The main outcome measure was actuarial freedom from PSA failure.
      RESULTS: Endorectal MRI did not add clinically meaningful information in 834 of
      our 1,025 cases (81%) after accounting for the prognostic value of PSA, biopsy
      Gleason score, clinical T stage and percent of positive biopsies. However, this
      modality provided a clinically and statistically relevant stratification of 5
      year PSA outcome in the remaining 191 patients at intermediate risk based on
      established prognostic factors. Specifically when endorectal MRI was interpreted
      as indicating extracapsular versus organ confined disease the relative risk of
      PSA failure was 3.6 (95% confidence interval 2.0 to 6.3), and 5-year actuarial
      freedom from PSA failure was 33% versus 72% (p <0.0001). CONCLUSIONS: Despite
      expert radiological interpretation endorectal MRI had potential clinical value in
      less than 20% of the cases in our study after accounting for established
      prognostic factors. While further study of the value of this modality for
      predicting clinical outcome after radical prostatectomy should be performed in
      this select cohort, routine use of endorectal MRI cannot be justified based on
      these data.

PMID- 10953142
TI  - Nocturnal incontinence in women: a hidden problem.
AB  - PURPOSE: We determined the prevalence of nocturnal incontinence and its
      association with other storage symptoms in a community population of women
      MATERIALS AND METHODS: We mailed the validated self-reporting Bristol female
      lower urinary tract symptom questionnaire to all 2,641 women 19 years old or
      older registered at a family physician practice in a major British city and
      analyzed the results. Main outcome measures were the prevalence of nocturnal
      incontinence and its correlation with other storage symptoms. RESULTS: A total of
      2,075 completed questionnaires (80%) were returned. The overall prevalence of
      nocturnal incontinence was 5.8%. However, the majority of women had nocturnal
      incontinence only occasionally and only 1% had it more than a third of the time.
      The prevalence of nocturnal incontinence increased in a linear fashion with age
      (chi-square test for linear trend p <0.005). Of the women with nocturnal
      incontinence 69% considered it troublesome. The odds of nocturnal incontinence
      were significantly increased when urge and stress incontinence, incontinence with
      no obvious cause, urgency, straining and nocturia were reported. CONCLUSIONS:
      Nocturnal incontinence in women is more common than generally supposed and
      troublesome. The rate of nocturnal incontinence increases with coexisting storage
      symptoms.

PMID- 10953143
TI  - Is intrinsic sphincter deficiency a complication of simple hysterectomy?
AB  - PURPOSE: Intrinsic sphincter deficiency may cause disabling stress urinary
      incontinence. While some pelvic operations are implicated as a cause of this
      condition, simple hysterectomy for benign disease is not recognized as one of
      them. We evaluated the association of simple hysterectomy with intrinsic
      sphincter deficiency. MATERIALS AND METHODS: We performed a case control study to
      assess the association of simple hysterectomy with intrinsic sphincter deficiency
      in a consecutive group of 387 incontinent women. From 1995 to 1997 we identified
      67 patients with and 67 controls without a history of hysterectomy. Further
      comparison was done after forming a subgroup at low risk for intrinsic sphincter
      deficiency. All patients were evaluated by a fluoroscopic urodynamic technique
      and abdominal leak point pressure was determined. RESULTS: Intrinsic sphincter
      deficiency was present in 48% of the 67 patients and 24% of the 67 controls. In
      the lower risk subgroup we noted this condition in 29 patients (52%) and 53
      controls (21%). CONCLUSIONS: In this population of incontinent women intrinsic
      sphincter deficiency, as diagnosed by low abdominal leak point pressure, appears
      to be a complication of simple hysterectomy.

PMID- 10953144
TI  - Retroperitoneal laparoscopic adrenalectomy in a pregnant woman with Cushing's
      syndrome.

PMID- 10953145
TI  - Primitive neuroectodermal tumor (extraskeletal Ewing's sarcoma) of the kidney
      with vena caval tumor thrombus.

PMID- 10953146
TI  - Synchronous ipsilateral renal adenocarcinoma, transitional cell carcinoma of the
      renal pelvis and metastatic renal lymphoma.

PMID- 10953147
TI  - Small bowel perforation after extracorporeal shock wave lithotripsy.

PMID- 10953148
TI  - Ureteral sciatic hernia demonstrated on retrograde urography and surgically
      repaired with Boari flap technique.

PMID- 10953149
TI  - Chyluria after radical nephrectomy treated with N-butyl-2-cyanoacrylate.

PMID- 10953150
TI  - Isolated recurrence of prostatic adenocarcinoma to the anterior urethra after
      radical prostatectomy.

PMID- 10953151
TI  - Bilateral synchronous testicular plasmacytoma.

PMID- 10953152
TI  - Successful use of Samarium 153 for emergency treatment of disseminated
      intravascular coagulation due to metastatic hormone refractory prostate cancer.

PMID- 10953153
TI  - Re: hemostatic control with flexible compression tape used during partial
      nephrectomy and organ salvage.

PMID- 10953154
TI  - Re: short and long-term morbidity of thoracoabdominal incision for nephrectomy: a
      comparison with the flank approach.

PMID- 10953155
TI  - Re: early post-prostatectomy pelvic floor biofeedback.

PMID- 10953156
TI  - Long-term efficacy of simple behavioral therapy for daytime wetting in children.
AB  - PURPOSE: Behavioral therapy has proved benefit for children with daytime wetting
      but most studies have used biofeedback techniques and provide no long-term
      assessment of results. We previously reported similar results using simple
      behavioral therapy without biofeedback. We report the long-term efficacy of
      behavioral therapy for daytime wetting. MATERIALS AND METHODS: Our program of
      behavioral therapy included timed voiding, modification of fluid intake, positive
      reinforcement techniques and pelvic floor (Kegel) exercises to promote pelvic
      floor strengthening and relaxation. Questionnaires to assess therapeutic efficacy
      were mailed to patients who had completed therapy more than 1 year previously.
      RESULTS: A total of 48 patients responded. Mean ages at the time of the initial
      clinic visit and questionnaire were 8.2 and 12.9 years, respectively. Improvement
      in symptoms was noted in approximately 74% of the cases during the first year
      following therapy. At a mean of 4. 7 years after treatment 59.4% of the patients
      had improved daytime urinary control, 51.1% improved daytime urinary frequency
      and 45.6% improved daytime urinary urgency. The frequency of urinary tract
      infections decreased in 56.4% of the cases. Measures of psychological well-being
      were also noted to be improved in a majority of patients. A total of 77.3% of the
      patients stated that they would recommend the program to others. CONCLUSIONS:
      Simple behavioral therapy without biofeedback techniques is an effective and
      durable first line therapy for children with daytime wetting.

PMID- 10953157
TI  - Leiomyoma of the glans penis in a child.

PMID- 10953158
TI  - Proximal insertion of gubernaculum testis in normal human fetuses and in boys
      with cryptorchidism.
AB  - PURPOSE: We determine how the proximal gubernaculum testis is attached to the
      testis and epididymis in human fetuses, and compare these data with findings in
      boys who had undergone surgery for cryptorchidism. MATERIALS AND METHODS: We
      analyzed 280 testes and epididymides with the gubernacula of 140 well preserved,
      fresh human fetuses ranging from 10 to 35 weeks after conception with no
      detectable congenital malformations and 36 undescended testes of 28 boys 2 to 15
      years old (mean age 6.8) who had undergone surgery for cryptorchidism. In both
      groups the different conformations of the relationship among the proximal
      gubernaculum, testis and epididymis were classified according to a system used
      for patients with cryptorchidism. In group A the gubernaculum is attached to the
      testis and epididymis, in group B the gubernaculum is attached only to the testis
      with a tail disjunction epididymal anomaly, in group C the gubernaculum is
      attached only to the testis with total disjunction of the epididymis, in group D
      the gubernaculum is attached only to the epididymal tail and in group E there are
      no attachments among gubernaculum, testis and epididymis. RESULTS: Of the 280
      fetal testes studied 194 (69.2%) were in the abdomen, 38 (13. 57%) in the
      inguinal canal and 48 (17.14%) in the scrotum. There were 277 cases (98.9%) in
      group A and 3 (1.1%) in group B. Of the 36 undescended testes analyzed 2 (5.6%)
      were abdominal and 34 (94.4%) were inguinal. There were 26 cases (72.2%) in group
      A, 8 (22.2%) in group B and 2 in group D. CONCLUSIONS: In fetuses without
      congenital malformations or epididymal alterations, such as tail disjunction or
      elongated epididymis, the proximal portion of the gubernaculum was attached to
      the testis and epididymis in all cases. In undescended testes there was an
      increased incidence of paratesticular structure malformations accompanied by
      gubernacular attachment anomalies compared to the testes in normal fetuses.

PMID- 10953159
TI  - Tumor necrosis factor-alpha represses androgen sensitivity in the LNCaP prostate
      cancer cell line.
AB  - PURPOSE: Prostate tumor progression is characterized by development of androgen
      independence and a heterogeneous distribution of the androgen receptor (AR).
      Tumor necrosis factor alpha (TNFalpha) has been demonstrated to contribute to the
      progression of several cancers and thus may play a role in prostate cancer
      progression. Accordingly, we examined if prostate cancers express TNFalpha and
      the effect of TNFalpha on androgen sensitivity and AR expression in LNCaP
      prostate cancer cells. MATERIALS AND METHODS: Immunohistochemical analysis of
      prostate tissues, ELISA, and northern blotting of LNCaP cell lines were carried
      out for detection of tumor necrosis factor-alpha (TNFalpha). To see the effect of
      TNFalpha on androgen receptor (AR), western blotting and northern blotting were
      performed after extraction of total protein and total RNA from LNCaP cells.
      Regulation of androgen-sensitivity by TNFalpha was investigated with cell
      proliferation assay and luciferase assay using PSA promoter after transfection of
      LNCaP cells. RESULTS: Immunohistochemical analysis demonstrated that TNFalpha
      protein was strongly expressed in epithelial cells of prostate cancer tissue but
      not in normal prostatic tissue. Basal level of TNFalpha in cell culture medium
      from LNCaP cells was very low. However, 12-O-tetradecanoylphorbol 13-acetate
      (TPA) induced TNFalpha secretion into medium up to 1600 pg/ml/day. Furthermore,
      24 hr. post-TPA treatment TNFalpha mRNA levels were increased 15-fold compared to
      pre-treatment levels. TNFalpha (0 to 30 ng./ml. for 4 days) repressed AR protein
      and mRNA levels in a dose-dependent fashion in LNCaP cells. Pre-treatment of
      cells with actinomycin D treatment revealed that repression of mRNA levels was
      exerted at the post-transcriptional level. TNFalpha inhibited the ability of 10-9
      M dihydrotestosterone (DHT) to induce LNCaP cell proliferation and activation of
      the prostate specific antigen (PSA) gene promoter. This inhibition was partially
      reversed by overexpression of transgenic androgen receptor. CONCLUSIONS: TNFalpha
      is present and inducible in prostate cancer cells and short-term TNFalpha
      diminishes androgen-sensitivity in LNCaP cells through down-regulation of AR
      protein and mRNA levels. These results suggest that TNFalpha may play a role in
      the initiation of an androgen-independent state in prostate cancer through its
      ability to inhibit AR sensitivity in prostate cancer.

PMID- 10953160
TI  - Age-related changes in contractile responses of rabbit lower urinary tract to
      endothelin.
AB  - PURPOSE: As there are significant amounts of endothelin (ET) receptors in the
      mammalian urinary tract, we investigated the pharmacological properties and
      localization of ET receptors in the rabbit lower urinary tract as a function of
      age. MATERIALS AND METHODS: The characteristics of ET receptors in bladder dome,
      trigone and urethra of 6 weeks and 6 months old male rabbits were determined
      using muscle bath and autoradiographic techniques. RESULTS: ET-1 produces
      significant contractile responses in smooth muscle strips from bladder dome,
      trigone, and urethra in both 6 weeks and 6 months old rabbits. Although there was
      no significant difference in the maximum contractile response of urethral muscle
      strips to ET-1 between 6 weeks and 6 months old rabbits, the maximum responses to
      ET-1 were higher in both bladder dome and trigone of 6 weeks than 6 months old
      rabbits. A selective ETA receptor antagonist, BQ 610, shifted the concentration
      response curve to ET-1 to the right without decreasing maximal contractile
      responses in all regions from both age groups, whereas a selective ETB receptor
      antagonist, IRL 1038, had no significant effect on the contractile response in
      these tissues. Autoradiographic studies indicate that both ET receptor subtypes
      are expressed in bladder dome, trigone, and urethra with the ETA subtype being
      located only in the smooth muscle layers and the ETB subtype being located in
      both the urothelial and smooth muscle layers. CONCLUSION: Our data indicate the
      presence of region- and age-dependent differences in the contractile properties
      of ET receptors in the male rabbit lower urinary tract. Although both ETA and ETB
      receptor subtypes are present in the smooth muscle layers, the ETA receptor is
      the sub-type that is primarily involved in the mediation of contractions.

PMID- 10953161
TI  - Suppression of primary tumor growth and the progression to metastasis with p53
      adenovirus in human prostate cancer.
AB  - PURPOSE: Numerous advances have been made in gene therapy approaches for the
      treatment of solid tumors, including prostate cancer. While treatment of the
      primary tumor has been well investigated, little information is available
      regarding gene therapy techniques which might impact on the progression to
      metastatic disease. We investigate the ability of p53 adenovirus to suppress not
      only primary tumor growth, but also the progression to metastatic disease.
      Mutation of the p53 tumor suppressor gene has been associated with the
      progression of prostate cancer. In this study, we utilized a metastatic model for
      human prostate cancer to determine if introduction of the wild-type p53 gene
      using an adenoviral vector (rAd-p53) impacted on primary tumor growth as well as
      the progression to metastatic disease. MATERIALS AND METHODS: For our studies, we
      used the human prostate cancer cell line PC-3, which has a homozygous loss of p53
      expression. Expression of exogenous p53 as well as p21 induction at various time
      points after infection with rAd-p53 was determined in vitro. In vivo studies were
      performed in nude mice following orthotopic (intraprostatic) injection of PC-3
      cells. Primary tumor growth as well as the progression to metastatic disease was
      assessed following rAd-p53 treatment. RESULTS: In vitro studies demonstrated high
      levels of p53 gene expression as well as the induction of p21 gene expression.
      Infection of PC-3 cells with rAd-p53 resulted in marked growth inhibition, as
      well as wide-spread fragmentation of nuclei and secretion of nuclear matrix
      proteins into the culture medium consistent with the process of apoptosis. In
      vivo studies demonstrated that a single injection of rAd-p53 into an established
      orthotopic prostate tumor resulted not only in primary tumor growth suppression
      (treated = 97.5 +/- 25.3 mm.3 versus control = 393.4 +/- 67.2 mm.3; p = 0.0002)
      but also reduced the frequency of progression to metastatic disease (treated = 8
      of 19 versus control = 18 of 19; p = 0.001). CONCLUSION: These experiments
      demonstrate that a single injection of rAd-p53 into an established orthotopic
      prostate tumor results not only in suppression of primary tumor growth, but also
      in a reduction of the frequency of progression to metastatic disease. These
      results suggest that a rAd-p53 gene therapy strategy may be useful in the
      treatment of human prostate cancer.

PMID- 10953163
TI  - Expression of E-, P-, n-cadherins and catenins in human bladder carcinoma cell
      lines.
AB  - PURPOSE: Cadherins are cell surface glycoproteins that mediate Ca2+-dependent,
      homophilic cell-cell adhesion. The classical cadherins, E-, P- and N-cadherins,
      are known to self-associate from their extracellular domain, while their
      cytoplasmic domain interacts with either beta-catenin or plakoglobin (gamma
      catenin), which in turn is bound to alpha-catenin that links the complex to the
      actin cytoskeleton. The aim of the present study was to analyze the expression of
      E-, P- and N-cadherins and catenins in human bladder carcinoma cells. MATERIALS
      AND METHODS: Five human bladder carcinoma cell lines, representing a variety of
      differentiation states, were grown in cell culture. We performed a cell
      aggregation assay, specific for biological cadherin activity. The expression of
      cadherins and catenins was analyzed by immunocytochemistry, Western blotting and
      RT-PCR. The interactions between cadherins and catenins were assessed by
      immunoprecipitation. RESULTS: We observed a reduced E-cadherin expression in the
      poorly differentiated and invasive-tumor derived cells. Interestingly,
      immunofluorescence study reveals the persistent localization of catenins at
      intercellular contacts in two E-cadherin deficient cell lines (T24 and TCCSUP)
      which yet exhibit an epithelial-like morphology and a calcium-dependent adhesive
      capacity. This suggests that other cadherin(s) are expressed in these both cell
      lines. P-cadherin, another epithelial cadherin, is expressed only in E-cadherin
      positive cells. On the other hand, N-cadherin is present at cell-cell borders in
      the very anaplastic cell lines, T24 and TCCSUP, and is able to link beta-catenin
      or plakoglobin. CONCLUSION: These results indicate that N-cadherin may
      participate in intercellular adhesion, while facilitating bladder tumorigenesis.

PMID- 10953162
TI  - Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate
      cancer in vivo.
AB  - PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme which catalyzes the
      formation of prostaglandins from arachidonic acid, is expressed in prostate
      cancer specimens and cell lines. To evaluate the in vivo efficacy of a COX-2
      inhibitor in prostate cancer, NS398 was administered to mice inoculated with the
      PC-3 human prostate cancer cell line. MATERIALS AND METHODS: A total of 28 male
      nude mice were inoculated subcutaneously with 1 million PC-3 cells. Tumors were
      palpable in all 28 animals 1 week after inoculation and mice were randomized to
      receive either vehicle (control) or NS398, 3 mg./kg. body weight,
      intraperitoneally three times weekly for 9 weeks. Tumors were measured at weekly
      intervals. After a 10-week experimental period, mice were euthanized and tumors
      were immuno- histochemically assayed for proliferation (PCNA), apoptosis (TUNEL)
      and microvessel density (MVD) (Factor-VIII-related antigen). Tumor VEGF content
      was assayed by Western blotting. RESULTS: NS398 induced a sustained inhibition of
      PC-3 tumor cell growth and a regression of existing tumors. Average tumor surface
      area from control mice was 285 mm.2 as compared with 22 mm.2 from treated mice
      (93% inhibition, p <0.001). Immunohistochemical analysis revealed that NS398 had
      no effect on proliferation (PCNA), but induced apoptosis (TUNEL) and decreased
      MVD (angiogenesis). VEGF expression was also significantly down regulated in the
      NS398-treated tumors. CONCLUSIONS: These results demonstrate that a selective COX
      2 inhibitor suppresses PC-3 cell tumor growth in vivo. Tumor growth suppression
      is achieved by a combination of direct induction of tumor cell apoptosis and down
      regulation of tumor VEGF with decreased angiogenesis

PMID- 10953164
TI  - Brefeldin A induces p53-independent apoptosis in primary cultures of human
      prostatic cancer cells.
AB  - PURPOSE: The objective of this study was to investigate growth-inhibitory and
      apoptotic activity of the experimental antitumor drug, brefeldin A (BFA), on
      primary cultures of human epithelial cells derived from prostatic
      adenocarcinomas. MATERIALS AND METHODS: Clonal assays were performed to evaluate
      the effects of BFA on growth of prostatic cancer cell strains. Loss of cell
      viability in response to BFA was assessed by trypan blue exclusion. Induction of
      apoptosis by BFA was evaluated by morphologic criteria, electrophoretic assay of
      DNA fragmentation, and a cell death ELISA. Immunoblots were used to monitor p53
      and pRB expression in response to BFA. RESULTS: BFA was growth-inhibitory at a
      half-maximal concentration of 5 ng./ml. (18 nM). Morphological manifestations of
      apoptosis were evident by 24 hours of treatment. Cell viability declined and the
      cell death ELISA indicated an 18-fold increase in apoptosis in BFA-treated versus
      untreated cells at 48 hours. DNA fragmentation was also seen at 48 hours. Levels
      of p53 were not altered by BFA, but pRB was maintained in a hypophosphorylated
      state by BFA treatment. CONCLUSIONS: BFA is a potent inducer of apoptosis in
      prostatic cancer cells via a p53-independent mechanism. Cells derived from low
      grade as well as high-grade cancers responded similarly to BFA. Since p53
      mediated pathways of apoptosis may frequently be abrogated in prostatic cancer
      cells, agents such as BFA that induce p53-independent cell death may be promising
      candidates for chemotherapeutic agents.

PMID- 10953165
TI  - Microsatellite alterations and loss of heterozygosity in Peyronie's disease.
AB  - PURPOSE: In the present study, we tested the hypothesis that microsatellite
      alterations (MSI) and loss of heterozygosity (LOH) are associated with Peyronie's
      disease. To test this hypothesis, we analyzed samples from patients with
      Peyronie's for MSI and LOH on chromosomes 3, 8 and 9 using 20 different genetic
      markers. MATERIALS AND METHODS: DNA was isolated from the penile fibrotic plaque,
      amplified using PCR, and analyzed for MSI and LOH on chromosomes 3, 8 and 9 using
      20 different polymorphic markers (D3S1228, D3S1298, D3S1560, D3S1745, D3S2396,
      D3S647, D8S133, D8S255, D8S259, D8S260, D8S262, D8S285, D8S298, D8S507, D8S528,
      D9S162, D9S171, D9S1747, D9S1748, and D9S273). Only 10 primers (D3S1560, D3S647,
      D3S1298, D8S262, D8S260, D8S528, D9S171, D9S1747, D9S273 and D9S1748) showed MSI
      and LOH in Peyronie's samples. Microsatellite alterations and LOH were analyzed
      by a PCR-based technique developed in our laboratory. RESULTS: This study
      demonstrates a high frequency of MSI and LOH in Peyronie's disease. Fourteen of
      35 cases (40%) showed MSI at a minimum of one locus, 6 of 35 cases (17%) at a
      minimum of 2 loci and three of 35 (8.5%) cases at three or more loci. D9S273
      locus showed highest MSI when compared with other loci examined in this study.
      For LOH, 14 of 35 cases (40%) were observed at a minimum of one locus, 5 of 35
      cases (14%) at minimum of two loci and one out of 35 cases (2.8%) showed LOH at
      three or more loci. The D3S1560 and D9S171 loci showed highest LOH when compared
      with all other loci examined in this study. CONCLUSION: This is the first report
      demonstrating that a high frequency of MSI and LOH is associated with Peyronie's
      disease, suggesting their role in the pathogenesis of this disease.

PMID- 10953166
TI  - In vitro selection of fluoroquinolone-resistant Neisseria gonorrhoeae harboring
      alterations in DNA gyrase and topoisomerase IV.
AB  - PURPOSE: We attempted to select increasingly fluoroquinolone-resistant strains of
      Neisseria gonorrhoeae in vitro and to assess whether selected mutants harbored
      alterations in the GyrA subunit of DNA gyrase and the ParC subunit of DNA
      topoisomerase IV, which were analogous to those in fluoroquinolone-resistant
      clinical isolates. MATERIALS AND METHODS: A fluoroquinolone-susceptible strain
      was exposed to norfloxacin in vitro. Selected mutants were sequentially exposed
      to norfloxacin, and this procedure was repeated. For 11 mutants, minimum
      inhibitory concentrations (MICs) of antimicrobial agents were determined, and
      mutations in the region corresponding to the quinolone resistance-determining
      region (QRDR) of the Escherichia coli gyrA gene and the analogous region of the
      parC gene were analyzed. RESULTS: Mutants obtained in one step exhibited
      significantly increased MICs of norfloxacin, ofloxacin and ciprofloxacin and had
      a single amino acid change in GyrA. Two-step mutants exhibited significantly
      higher norfloxacin MICs. Three of four two-step selected strains had single amino
      acid changes in both GyrA and ParC. Three-step mutants exhibited further
      increases in fluoroquinolone MICs and were assigned to the ciprofloxacin
      resistant category. Two had a double amino acid change in GyrA, and one had a
      double GyrA change and a single amino acid change in ParC. CONCLUSION: We
      selected fluoroquinolone-resistant strains that carried GyrA and ParC alterations
      analogous to those in clinical isolates. The serial accumulation of changes in
      the QRDR of GyrA and the analogous region of ParC was associated with a stepwise
      increase in fluoroquinolone resistance, although the development of additional
      alterations in other regions of GyrA and ParC or other mechanisms of
      fluoroquinolone resistance also might contribute to the enhancement in
      fluoroquinolone resistance. The clinical emergence of fluoroquinolone-resistant
      strains may be due to in-vivo stepwise selection of strains with genetic
      alterations in GyrA and ParC, as observed here in the in-vitro selection of
      fluoroquinolone-resistant mutants.

PMID- 10953167
TI  - CNS induced neurogenic cystitis is associated with bladder mast cell
      degranulation in the rat.
AB  - PURPOSE: To determine if bladder mast cell degranulation is involved in the
      genesis of neurogenic cystitis induced by pseudorabies virus (PRV) invasion of
      the central nervous system (CNS). MATERIALS AND METHODS: Rats received a total of
      4 x 106 plaque forming units (pfu) of PRV-Bartha in the abductor caudalis
      dorsalis (ACD) muscle. Granulated bladder mast cells per mm2 of bladder tissue
      and urine histamine content were monitored as the cystitis developed over the
      next few days. In a subgroup of rats, intravesical resiniferatoxin was used to
      remove capsaicin-sensitive sensory bladder afferents, while another subgroup was
      pretreated with a mast cell degranulator. RESULTS: PRV injection into the ACD
      muscle leads to neurogenic cystitis. Histamine levels were elevated in the urine
      of virus injected rats before any behavioral or microscopical signs of cystitis
      were present. When the cystitis became clinically manifest, urine histamine
      returned to control levels, and the number of granulated mast cells dropped
      significantly. Rats in which capsaicin-sensitive afferents had been removed did
      not show any signs of cystitis, or increase in urine histamine, or change in the
      number of granulated mast cells. Pretreatment of animals with a mast cell
      degranulator completely prevented the appearance of cystitis without altering the
      CNS disease. CONCLUSION: These results provide further evidence that mast cells
      are involved in neurogenic cystitis induced by changes in CNS activity.

PMID- 10953168
TI  - Solid-state 13 C and 31 P NMR analysis of urinary stones.
AB  - PURPOSE: We investigated the applicability of solid-state nuclear magnetic
      resonance (NMR) spectroscopy to obtain information about the structure and
      composition of renal calculi. MATERIALS AND METHODS: Various types urinary and
      bladder stones as well as a variety of presumed constituents were investigated
      using 13C and 31P magic-angle spinning (MAS) solid-state NMR. Different
      experimental methods were applied to differentiate resonances from
      crystalline/amorphous (immobile/mobile) as well as protonated/non-protonated
      moieties. The NMR spectra were analyzed using multiple-component numerical
      simulations and iterative fitting to identify and quantify the major amorphous or
      crystalline organic and inorganic components. RESULTS: By comparison of the NMR
      spectra for the various renal calculi with those obtained under similar
      conditions for various presumed components, it is demonstrated possible to
      unambiguously distinguish and quantify the major amorphous or crystalline organic
      and inorganic components. The components are identified in terms of their
      isotropic and anisotropic chemical shielding parameters, protonation or proximity
      of protons, and the degree of crystallinity/mobility. For the calculi
      investigated we have detected and quantified calcium oxalate, uric acid,
      struvite, and calcium phosphates that closely resemble brushite and calcium
      hydroxyapatite. CONCLUSIONS: Using 13C and 31P MAS NMR spectroscopy we have been
      able to account for 60 to 85% (by weight) of the constituents in the calculi
      investigated. The ability to identify and quantify both crystalline and amorphous
      components makes solid-state NMR an interesting new method for the compositional
      analysis of renal calculi.

PMID- 10953169
TI  - Does the absorbable fibrin adhesive bandage facilitate partial nephrectomy?
AB  - PURPOSE: To evaluate the ability of the absorbable fibrin adhesive bandage
      (AFAB), a prototype product comprising lyophilized fibrinogen and thrombin on a
      VicrylTM mesh backing, to seal the collecting system and control bleeding after
      partial nephrectomy. MATERIALS AND METHODS: Growing female pigs (n = 18)
      underwent left nephrectomy and a 40% (by length) right lower pole partial
      nephrectomy. One of three treatments was immediately applied: Conventional
      closure of the collecting system, ligation of visible segmental vessels,
      application of SurgicelTM with bolstering sutures to the renal capsule; AFAB
      application of up to two 4 x 4-inch AFABs held under pressure for 60 seconds;
      Placebo-application of a hemostatically inert VicrylTM bandage, visually
      identical to the AFAB. Blood loss and ischemic and total operative times were
      recorded, and abdominal computerized tomography (CT) was performed on
      postoperative day 6. Animals were sacrificed at 6 weeks to evaluate the remaining
      renal mass histologically. RESULTS: Compared with conventional therapy, use of
      the AFAB resulted in significantly less bleeding (13 versus 68 ml., p <0.001) and
      lower operative (7.2 versus 16.3 minutes, p <0.001) and ischemic times (3.4
      versus 7.8 minutes, p <0.001). Estimated blood loss in the placebo bandage group
      was dramatically higher (357 ml., p <0.001). Postoperative CT and histological
      sectioning suggested that the AFAB produces a stable, durable clot and that
      healing is at least as successful as with conventional treatment. CONCLUSION: Use
      of the AFAB facilitated performance of partial nephrectomy by reducing blood loss
      and ischemic and total operative times. The AFAB appears equivalent to
      conventional surgery in its ability to seal the collecting system.

PMID- 10953170
TI  - Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide
      synthase and heme oxygenase.
AB  - PURPOSE: To characterize the distribution of cholinergic nerves in the human
      corpus cavernosum (CC) and spongiosum (CS) using antibodies to the vesicular
      acetylcholine transporter (VAChT), and to compare this distribution to those of
      other transmitters/mediators or transmitter/mediator generating enzymes (heme
      oxygenases: HO-1 and HO-2; neuronal and endothelial NO synthases: nNOS and eNOS;
      vasoactive intestinal polypeptide: VIP; and tyrosine hydroxylase: TH), and to
      investigate NO- and carbon monoxide (CO)-mediated effects. MATERIALS AND METHODS:
      Immunocytochemistry, confocal laser scanning microscopy, radioimmunoassay, and
      functional in vitro studies. RESULTS: Along strands of smooth muscle in the CC
      and CS, rich numbers of VAChT-, nNOS-, VIP-, TH-, and very few HO-1
      immunoreactive (-IR) nerve fibers were observed. Immunoreactivities for VAChT and
      nNOS, VAChT and VIP, and nNOS and VIP, were generally found in the same varicose
      nerve terminals. TH-IR nerve fibers or terminals did not contain
      immunoreactivities for VAChT, NOS or VIP. In the endothelium lining penile
      arteries, immunoreactivities for eNOS, HO-1, and HO-2 were detected. Single
      endothelial cells, lining the sinusoidal walls of the CC and CS, were found also
      to contain eNOS and HO-immunoreactivities. Noradrenaline (NA)-contracted
      preparations of CC and CS were relaxed by NO, CO, carbachol and by electrical
      stimulation of nerves. Inhibition of NO synthesis abolished electrically- and
      carbachol-induced relaxation. In NA-activated strips, relaxation induced by
      exogenously applied NO, but not those by CO, were accompanied by increases in
      intracellular levels of cyclic GMP. CONCLUSIONS: VAChT, NOS and VIP are found in
      the same nerve terminals within the human CC and CS, suggesting that these
      terminals comprise a distinct population of parasympathetic, cholinergic nerves.
      Endothelially derived NO and the HO/CO system may have a complementary role in
      penile erection.

PMID- 10953171
TI  - The selectivity and specificity of the actions of the lipido-sterolic extract of
      Serenoa repens (Permixon) on the prostate.
AB  - PURPOSE: To investigate the effects of the phytotherapeutic agent, Permixon(R),
      on primary cultures of fibroblast and epithelial cells from the prostate,
      epididymis, testes, kidney, skin and breast and to determine the selectivity and
      specificity of the action of the drug. MATERIALS AND METHODS: All primary
      cultures were examined by electron microscopy before and following treatment with
      Permixon(R) (10 microg./ml.). In addition the apoptotic index was assessed by
      flow cytometry employing propidium iodide as a fluorophore. The impact of the
      drug on 5alpha-reductase (5alphaR) isoenzymes was also tested utilizing a pH
      specific assay. RESULTS: There were changes in the morphology of prostate cells
      after treatment including accumulation of lipid in the cytoplasm and damage to
      the nuclear and mitochondrial membranes; no similar changes were observed in
      other cells. Permixon(R) increased the apoptotic index for prostate epithelial
      cells by 35% and 12% in the prostate stromal/fibroblast. A lesser apoptotic
      effect was demonstrated in skin fibroblast (3%) whereas none of the other primary
      cultures showed any increase in apoptosis when compared with the controls.
      Permixon(R) was also an effective inhibitor of both 5alphaR type I and II
      isoenzymes in prostate cells, but other cells showed no inhibition of 5alphaR
      activity following treatment with the plant extract. CONCLUSIONS: This
      investigation demonstrated the selectivity of the action of Permixon(R) for
      prostate cells. The morphological changes in the prostate are accompanied by an
      increase in the apoptotic index along with an inhibition in the activity of the
      nuclear membrane bound 5alphaR isoenzymes. No similar changes were observed in
      any of the other cells under investigation.

PMID- 10953172
TI  - Rabbit corpus cavernosum smooth muscle shows a different phosphodiesterase
      profile than human corpus cavernosum.
AB  - PURPOSE: Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of
      cAMP/cGMP secondary messenger systems. Fluctuations in the level of cyclic
      nucleotides control the smooth muscle tone of corpus cavernosum. It had been
      shown that milrinone, a PDE3 inhibitor, was as potent as sildenafil, a PDE5
      inhibitor, in relaxing human corpus cavernosum. However, milrinone is much less
      effective in relaxing rabbit corpus cavernosum than sildenafil. PDEs in rabbit
      corpus cavernosum were characterized and organ bath experiments were carried out
      in an attempt to search for the biochemical basis of this species difference.
      MATERIALS AND METHODS: In a biochemical study, PDE isozymes from rabbit corpus
      cavernosum were isolated by FPLC and characterized by PDE assay. In organ bath
      experiments, rabbit corpus cavernous tissue strips were precontracted and
      increasing doses of various inhibitors were added. RESULTS: The major PDE in
      rabbit corpus cavernosum is PDE5. There are small amounts of PDE2 and PDE1. PDE3,
      which contributes significantly to the total PDE activity in human corpus
      cavernosum, is apparently lacking in rabbit corpus cavernosum. Organ bath
      experiments with isotype-specific inhibitors confirm this conclusion. CONCLUSION:
      The distribution of PDE isozymes in corpus cavernosum is different in human and
      in rabbit. This could be the biochemical basis for the differential effects of
      milrinone in relaxing rabbit and human corpus cavernosum. Our study emphasizes
      the importance of a more complete understanding of the tissue distribution of
      targeted proteins in an animal model before applying the results to humans.

PMID- 10953173
TI  - An IL-1 alpha susceptibility polymorphism in Alzheimer's disease:new fuel for the
      inflammation hypothesis.

PMID- 10953174
TI  - Best treatment for intracranial arterial stenosis? 50 years of uncertainty. The
      WASID Investigators.

PMID- 10953175
TI  - Cell transplant therapy for stroke: hope or hype.

PMID- 10953176
TI  - Practice parameter: screening and diagnosis of autism: report of the Quality
      Standards Subcommittee of the American Academy of Neurology and the Child
      Neurology Society.
AB  - Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it
      often remains unrecognized and undiagnosed until or after late preschool age
      because appropriate tools for routine developmental screening and screening
      specifically for autism have not been available. Early identification of children
      with autism and intensive, early intervention during the toddler and preschool
      years improves outcome for most young children with autism. This practice
      parameter reviews the available empirical evidence and gives specific
      recommendations for the identification of children with autism. This approach
      requires a dual process: 1) routine developmental surveillance and screening
      specifically for autism to be performed on all children to first identify those
      at risk for any type of atypical development, and to identify those specifically
      at risk for autism; and 2) to diagnose and evaluate autism, to differentiate
      autism from other developmental disorders.

PMID- 10953177
TI  - Association of an interleukin 1 alpha polymorphism with Alzheimer's disease.
AB  - BACKGROUND: Retrospective epidemiologic studies suggest that individuals exposed
      to anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs have a
      lower probability of developing AD as well as an older age at onset for the
      illness. Neuroinflammation may play an important role in the pathogenesis of AD.
      Interleukin 1 (IL-1), a potent proinflammatory cytokine, is colocalized
      immunohistochemically to neuritic plaques, a requisite neuropathologic feature
      for AD. A polymorphism in the 5'-flanking regulatory region at -889 of the IL-1
      alpha gene (a C-to-T transition designated as IL-1A[-889] allele 2) may cause an
      overexpression of IL-1 alpha, a finding shown to be associated with inflammatory
      diseases. The IL-1A(-889) allele 2 polymorphism may be associated with AD
      pathogenesis. METHODS: A total of 259 patients with AD and 192 nondemented
      control subjects were included from two different centers (Indianapolis, IN, and
      Munich, Germany). Genotyping for APOE alleles and IL-1A(-889) allele 2 was
      performed by PCR-based amplification followed by restrictive endonuclease
      digestion. Statistical analyses were conducted by center-, gender group-, and age
      group-stratified Mantel-Haenszel odds ratios, CI, and p values. RESULTS: The
      allele frequency of IL-1A(-889) allele 2 was 46% in clinically diagnosed patients
      with probable AD versus 34% in control subjects from the combined centers.
      CONCLUSION: The authors found an increased risk for AD with an estimated Mantel
      Haenszel odds ratio of 1.68 (95% CI 1.1 to 2.6; p = 0.022) for heterozygous
      carriers and 7.2 (95% CI 2.0 to 24.5; p = 0.003) for individuals homozygous for
      IL-1A(-889) allele 2. They found no evidence for an interaction between the IL-1A
      and the apoE epsilon 4 polymorphisms (carriers and homozygotes), age, or gender
      with regard to conferred risk. The data strongly support an association between
      the IL-1A(-889) allele 2, especially in homozygotes, and later-onset AD.

PMID- 10953178
TI  - Rates of hippocampal atrophy correlate with change in clinical status in aging
      and AD.
AB  - BACKGROUND: The cognitive continuum in the elderly population can be conceptually
      divided into those who are functioning normally (control subjects), those with a
      mild cognitive impairment (MCI), and those with probable AD. OBJECTIVES: To test
      the hypothesis that the annualized rates of hippocampal atrophy differ as a
      function of both baseline and change in clinical group membership (control, MCI,
      or AD). METHODS: The authors identified 129 subjects from the Mayo Clinic AD
      Research Center/AD Patient Registry who met established criteria for normal
      control subjects, MCI, or probable AD, both at entry and at the time of a
      subsequent clinical follow-up evaluation 3 +/- 1 years later. Each subject
      underwent an MRI examination of the head at the time of the initial assessment
      and at follow-up clinical assessment; the annualized percentage change in
      hippocampal volume was computed. Subjects who were classified as controls or
      patients with MCI at baseline could either remain cognitively stable or could
      decline to a lower functioning group over the period of observation. RESULTS: The
      annualized rates of hippocampal volume loss for each of the three initial
      clinical groups decreased progressively in the following order: AD > MC >
      control. Within the control and MCI groups, those who declined had a
      significantly greater rate of volume loss than those who remained clinically
      stable. The mean annualized rates of hippocampal atrophy by follow-up clinical
      group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI
      decliner 3.69%, AD 3. 5%. CONCLUSION: Rates of hippocampal atrophy match both
      baseline cognitive status and the change in cognitive status over time in elderly
      persons who lie along the cognitive continuum from normal to MCI to AD.

PMID- 10953179
TI  - Symptomatic intracranial atherosclerosis: outcome of patients who fail
      antithrombotic therapy.
AB  - OBJECTIVE: To determine the prognosis of patients with symptomatic intracranial
      atherosclerosis who fail antithrombotic therapy. BACKGROUND: The outcome of
      patients with symptomatic intracranial atherosclerosis who fail antithrombotic
      therapy is unknown. These patients may represent the target group for
      investigation of more aggressive therapies such as intracranial angioplasty.
      METHODS: The authors performed a chart review and telephone interview of patients
      with symptomatic intracranial atherosclerosis identified in the Stanford Stroke
      Center clinical database. A Cox regression model was created to identify factors
      predictive of failure of antithrombotic therapy. The authors generated Kaplan
      Meier survival curves to determine the timing of recurrent TIA, stroke, or death
      after failure of antithrombotic therapy. RESULTS: Fifty-two patients had
      symptomatic intracranial atherosclerosis and fulfilled entry criteria. Twenty
      nine of the 52 patients (55.8%) had cerebral ischemic events while receiving an
      antithrombotic agent (antiplatelet agents [55%], warfarin [31%], or heparin
      [14%]). In a Cox regression model, older age was an independent predictor of
      failure of antithrombotic therapy, and warfarin use was associated with a
      decrease in risk. Recurrent TIA (n = 7), nonfatal/fatal stroke (n = 6/1), or
      death (n = 1) occurred in 15 of 29 (51.7%) of the patients who failed
      antithrombotic therapy. The median time to recurrent TIA, stroke, or death was 36
      days (95% CI 13 to 59). CONCLUSIONS: Patients with symptomatic intracranial
      atherosclerosis who fail antithrombotic therapy have extremely high rates of
      recurrent TIA/stroke or death. Recurrent ischemic events typically occur within a
      few months after failure of standard medical therapy. The high recurrence risk
      observed warrants testing of alternative treatment strategies such as
      intracranial angioplasty.

PMID- 10953180
TI  - Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction
      of stroke outcome.
AB  - BACKGROUND: The prognostic value of the biochemical changes seen with proton MR
      spectroscopy (1H MRS) in ischemic stroke was examined. Acute diffusion-weighted
      imaging (DWI) was used to identify regions of ischemia for 1H MRS voxel
      localization. METHODS: Nineteen patients had 36 1H MRS studies, 13 patients
      acutely (mean, 11.1 hours), 10 subacutely (mean, 3.9 days), and 13 at outcome
      (mean, 82 days). Single-voxel, long-echo, timepoint-resolved spectroscopy was
      used to obtain lactate, n-acetylaspartate (NAA), choline, and creatine levels
      from the infarct core. Outcome measures were final infarct volume and clinical
      assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale).
      RESULTS: Acute lactate/choline ratio correlated more strongly with clinical
      outcome scores (r = 0.76 to 0.83; p < 0.01) and final infarct size (r = 0. 96; p
      < 0.01) than acute DWI lesion volume or acute NAA/choline ratio. Combination of
      acute lactate/choline ratio with acute DWI lesion volume improved prediction of
      all outcome scores (R2 = 0.80 to 0.90). The predictive effect of acute
      lactate/choline ratio was independent of acute DWI lesion volume (p < 0.001). In
      subacute and chronic infarction, both lactate/choline and NAA/choline ratios
      continued to correlate with outcome (p < 0.05). At the chronic stage, persistent
      lactate/choline ratio elevation strongly correlated with outcome measures (r =
      0.71 to 0.87). CONCLUSION: Lactate/choline ratio measured in the acute infarct
      core by 1H MRS improves the prediction of stroke outcome and provides prognostic
      information complementary to DWI. Lactate/choline ratio could be used as an
      additional marker to select patients for acute and chronic therapies.

PMID- 10953181
TI  - Electrographic seizures in neonates correlate with poor neurodevelopmental
      outcome.
AB  - OBJECTIVE: To quantify the number, duration, and intensity of electrographic
      seizures (ESz) in neonates and to compare the outcome of neonates with ESz with
      those who were at risk but did not have ESz recorded. METHODS: The EEG and
      outcome data were reviewed from 68 infants who met at-risk criteria for neonatal
      seizures and underwent prolonged continuous EEG monitoring. Forty infants had
      ESz. The control group contained 28 infants monitored for at least 18 hours and
      found not to have ESz. Outcomes for both groups were evaluated using hospital and
      follow-up clinic records and a standardized telephone interview. RESULTS: The
      etiology of ESz included asphyxia (n = 23), stroke (n = 7), and other (n = 10,
      intraparenchymal, subdural, and subarachnoid bleeding; meningitis; sepsis;
      hyponatremia; and unknown). The cumulative recorded ESz duration was 8 minutes to
      30 hours. Forty-three percent of infants with ESz spent 38 minutes to 32 hours in
      electrographic status. Despite doses of 40 mg/kg of phenobarbital and 20 mg/kg of
      phenytoin, 30% of infants continued to have ESz. Ten infants with ESz and one
      without died from causes related to neurologic instability. The occurrence of ESz
      was correlated with microcephaly (p = 0.04), severe cerebral palsy (CP) (p =
      0.03), and failure to thrive (p = 0. 03). In the subgroup of infants with
      asphyxia, those with ESz were more likely to die of neurologic causes (p = 0.02)
      and have microcephaly (p = 0.05) or severe CP (p = 0.04). Additionally, those
      with the greatest number of ESz were more likely to have these severe outcomes.
      CONCLUSION: The authors' data indicate an association between the amount of
      electrographic seizure activity and subsequent mortality and morbidity in at-risk
      infants in general and in infants with perinatal asphyxia. Only with more
      effective treatment of neonatal electrographic seizures can their potential
      contribution to poor neurodevelopmental outcome, independent of degree of insult,
      be ascertained.

PMID- 10953182
TI  - 14-3-3 testing in diagnosing Creutzfeldt-Jakob disease: a prospective study in
      112 patients.
AB  - OBJECTIVE: To study the sensitivity and specificity of 14-3-3 testing in a
      prospective series of patients suspected of having Creutzfeldt-Jakob disease
      (CJD). BACKGROUND: The 14-3-3 protein immunoassay on CSF has favorable test
      characteristics as a premortem diagnostic tool in CJD. However, the 14-3-3
      protein is a normal cellular protein expressed in various tissues, and its
      presence in CSF reflects extensive destruction of brain tissue as in CJD, but
      also in ischemic stroke and meningoencephalitis. METHODS: 14-3-3 was tested in
      the CSF of a prospective series of 110 consecutive patients suspected of having
      CJD. RESULTS: The sensitivity was 97% and the specificity was 87% in this series.
      False-positive results were mainly caused by stroke and meningoencephalitis.
      CONCLUSION: The 14-3-3 protein is a highly sensitive and specific marker for CJD
      when used in the appropriate clinical context.

PMID- 10953183
TI  - Inherited prion encephalopathy associated with the novel PRNP H187R mutation: a
      clinical study.
AB  - OBJECTIVE: To describe a variant of prion encephalopathy associated with the
      recently identified H187R mutation in the prion protein (PRNP) gene. METHODS: The
      authors studied a multigenerational American family with nine affected
      individuals. Clinical examination included imaging, EEG, and CSF analysis with 14
      3-3 protein testing. Histopathology was characterized by examination of a brain
      biopsy from an H187R mutation-positive patient. RESULTS: The disease in this
      family is caused by the PRNP H187R mutation and characterized by autosomal
      dominant inheritance, median age at disease onset of 42 years (range 33 to 50
      years), and median duration of illness of 12 years (range 8 to 19 years).
      Clinical signs include progressive dementia, ataxia, myoclonus, and seizures.
      Histopathologic features consist of distinctive "curly" prion protein deposits
      with a strictly laminar distribution in the cerebral cortex and minimal
      astrogliosis in the absence of amyloid plaques or spongiosis. CONCLUSION: A
      variant of prion encephalopathy associated with the novel H187R mutation in the
      PRNP gene displays distinctive clinical and immunostaining characteristics that
      further expand the boundaries of human prion disease.

PMID- 10953184
TI  - Hemispheric asymmetries of limb-kinetic apraxia: a loss of deftness.
AB  - OBJECTIVES: Unlike patients with ideomotor apraxia who make temporal and spatial
      errors and patients with ideational or conceptual apraxia who make content
      errors, patients with limb-kinetic apraxia have loss of deftness, including fine
      and precise movements, independent finger movements, and difficulty coordinating
      simultaneous movements. This study was conducted to learn the relationship
      between limb-kinetic apraxia and hemisphere dysfunction by using selective
      hemisphere anesthesia, the Wada test. METHODS: Subjects were 90 patients
      undergoing Wada testing for intractable epilepsy. They were divided into typical
      (right-handed with left hemisphere language dominance) and atypical (nonright
      handed, or without left hemisphere language dominance). Before and during Wada
      testing, subjects were shown line drawings of tools, four for each hand tested.
      After being shown each picture, subjects pantomimed the use of this tool. A
      behavioral neurologist and neuropsychologist scored the pantomimes for the
      presence of limb-kinetic errors. RESULTS: For the typical group, during left
      hemisphere anesthesia, the limb-kinetic errors made by the right and left hands
      did not differ, but during right hemisphere anesthesia the left hand made more
      errors than the right. Unlike the typical subjects, when the left hemisphere was
      anesthetized, the atypical subjects made more errors with their right hands than
      left. However, similar to the typical subjects with right hemisphere anesthesia,
      the atypical subjects made more left- than right-hand limb-kinetic errors.
      CONCLUSIONS: For people with typical brain organization, the left hemisphere
      mediates motor deftness for both hands, but the right hemisphere primarily
      controls deftness for the left hand. For people with atypical brain organization,
      each hemisphere primarily controls deftness for the contralateral hand.

PMID- 10953185
TI  - Neuroimages: local hyperhydrosis of the left forearm.

PMID- 10953186
TI  - Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy.
AB  - OBJECTIVE: To determine the percentage of sporadic olivopontocerebellar atrophy
      (sOPCA) patients who later develop multiple system atrophy (MSA). METHODS:
      Observations of the course of 51 sOPCA patients 20 years of age or older
      initially evaluated in an ataxia clinic over 14 years and followed at 3- to 6
      month intervals for 3 months to 10 years (median 2.5 years, interquartile range 5
      months to 4 years). RESULTS: Seventeen patients evolved to develop MSA, whereas
      the remaining 34 manifested only progressively worsening cerebellar ataxia. The
      features of the MSA cases included autonomic failure and parkinsonism in 10
      patients, autonomic failure without parkinsonism in six, and parkinsonism without
      autonomic failure in one. Using survival analysis methods, the authors estimated
      that 24% of subjects in this population will evolve to MSA within 5 years of the
      onset of sOPCA symptoms (95% CI 10% to 36%). An older age at onset of symptoms
      and a shorter time from onset of symptoms to first presentation in a neurology
      specialty clinic were both highly predictive of evolution to MSA. Six of the 17
      patients who evolved to MSA died 4 months to 5 years after they had met
      diagnostic criteria for MSA. The estimated median survival time from time of
      transition was 3.5 years. In contrast, death occurred in only one of the 34
      patients with sOPCA who did not evolve to MSA. Autopsy examination of all six
      patients with MSA who died confirmed the diagnosis. CONCLUSIONS: Approximately
      one-fourth of sporadic olivopontocerebellar atrophy patients will evolve to
      multiple system atrophy within 5 years, and this transition carries a poor
      prognosis for survival. Older age at onset of ataxia and earlier presentation in
      a neurologic specialty clinic predicted transition to MSA.

PMID- 10953187
TI  - Variability and validity of polymorphism association studies in Parkinson's
      disease.
AB  - BACKGROUND: In recent years, interest in gene-environment interactions has
      spurred a great number of association studies on polymorphism of different genes.
      OBJECTIVE: To review case-control studies of genetic polymorphisms in PD, and
      perform meta-analysis of individual gene polymorphism. METHODS: The authors
      searched the Medline database (PubMed) for publications (English language) from
      January 1966 to November 1999 for association studies in PD. The key words used
      were "PD" and "polymorphism." The authors supplemented the search with relevant
      references quoted in these published articles. Those with four or more
      independent studies of a specific gene polymorphism were subjected to meta
      analysis, with the exception of cytochrome-P450 enzyme polymorphisms, for which
      meta-analyses results were already available in the literature. RESULTS: The
      authors identified 84 studies on 14 genes, including dopamine receptors (DRD2 and
      DRD4), dopamine transporter (DAT), monoamine oxidase (MAOA and MAOB), catechol-O
      methyltransferase (COMT), N-acetyltransferase 2 (NAT2), APOE, glutathione
      transferase (GSTT1, GSTM1, GSTP1, and GSTZ1), and mitochondrial genes (tRNAGlu
      and ND2). Four polymorphisms showed significant association with PD: slow
      acetylator genotypes of NAT2 (PD:control OR = 1.36), allele >188bp of the MAOB
      (GT)n polymorphism (OR = 2.58), the deletion allele of GSTT1 (OR = 1.34), and
      A4336G of tRNAGlu (OR = 3.0). No significant differences were found for the other
      genes. CONCLUSION: Significant associations with PD were found in polymorphisms
      of NAT2, MAOB, GSTT1, and tRNAGlu. Although significant association does not
      imply a causal relationship between the presence of the polymorphisms and PD
      pathogenesis, their pathophysiologic significance should be studied further.

PMID- 10953188
TI  - Motor impairment in PD: relationship to incident dementia and age.
AB  - OBJECTIVE: To analyze the relationship of specific motor impairment in idiopathic
      PD to incident dementia. BACKGROUND: The total Unified PD Rating Scale (UPDRS)
      motor score at baseline has been associated with an increased risk of developing
      dementia in PD. METHODS: A cohort of 214 nondemented community-dwelling patients
      with PD was followed annually with neurologic and neuropsychological evaluations.
      The association of baseline motor impairment with incident dementia was analyzed
      using Cox proportional hazards models. Facial expression, tremor, rigidity, and
      bradykinesia were analyzed as part of subscore A (indicative of dopaminergic
      deficiency); speech and axial impairment were analyzed as part of subscore B
      (indicative of predominantly nondopaminergic deficiency). The correlation between
      the six motor domains and age was also analyzed. RESULTS: Of 173 patients
      followed for at least 1 year, 50 became demented according to the Diagnostic and
      Statistical Manual of Mental Disorders, revised 3rd edition (DSM III-R) criteria
      (mean follow-up, 3.6 +/- 2. 2 years). When both subscores A and B were entered
      into the Cox model, subscore B was associated with incident dementia (relative
      risk = 1.19; 95% CI, 1.09 to 1.30; p = 0.0001), in addition to gender, age, and
      education, whereas subscore A was not (relative risk = 1.03; 95% CI, 0.99 to
      1.07; p = 0.19). Of the six motor domains, speech and bradykinesia were
      associated with incident dementia (p < 0.05), and axial impairment approached
      significance (p = 0.06). Only axial impairment was correlated with age
      (correlation coefficient = 0.32; p < 0.001). CONCLUSION: The findings suggest
      that motor impairment mediated predominantly by nondopaminergic systems is
      associated with incident dementia in PD. Axial impairment may be the result of a
      combined effect of the disease and the aging process.

PMID- 10953189
TI  - Cerebral blood flow and glucose metabolism in mitochondrial disorders.
AB  - OBJECTIVE: To investigate cerebral metabolism by 2-[18F]fluorodeoxy-d-glucose
      (FDG) uptake using PET and cerebrovascular reverse capacity by transcranial
      Doppler sonography (TCD) in different mitochondrial diseases (mitochondrial
      myopathy; mitochondrial encephalopathy, lactacidosis, and stroke-like episodes
      [MELAS]; and chronic external ophthalmoplegia). BACKGROUND: Previous studies on
      individual patients with mitochondriopathies revealed abnormal accumulations of
      mitochondria in endothelium, smooth muscle cells, and pericytes of blood vessels
      in different parts of the nervous system (cerebrum, cerebellum, sural nerve) and
      skeletal muscle. On this basis, some investigators suggested a pathogenic role of
      vascular involvement in the MELAS syndrome and other encephalopathies. smhd1
      DESIGN/METHODS: The authors investigated neuronal metabolism and cerebrovascular
      involvement with PET in 5 cases and with TCD with acetazolamide stimulation in 15
      cases. The patients were divided into three groups: 1) interictal MELAS (n = 4);
      2) progressive external ophthalmoplegia (n = 6); and 3) pure mitochondrial
      myopathy and neuropathy (n = 5). The results were compared with those from
      matched normal control subjects. The diagnoses were based on clinical phenotype
      as well as histopathologic and molecular analysis. RESULTS: Cerebral glucose
      uptake was impaired in all patients, both with and without CNS symptoms,
      particularly in the occipital and temporal lobes. The vasoreactivity of the small
      arterioles to acetazolamide did not differ significantly between the patients and
      healthy control subjects or between the different groups of mitochondrial
      disorders. CONCLUSIONS: MELAS does not appear to be a functional disturbance of
      arterioles leading to an ischemic vascular event. The clinical symptoms in MELAS
      are not the result of a mitochondrial angiopathy but are the consequences of a
      mitochondrial cytopathy affecting neurons or glia. There is no correlation
      between the decreased glucose metabolism and the duration of the disease.

PMID- 10953190
TI  - Long-term interferon beta-1b therapy for MS: is routine thyroid assessment always
      useful?
AB  - BACKGROUND: The authors previously reported on the development of thyroid
      dysfunction and autoimmunity during 1-year treatment of patients with MS with
      interferon-beta 1b (IFN beta-1b). OBJECTIVE: To evaluate the evolution of
      incident thyroid disease and the possible development of more thyroid disease
      during longer term therapy. PATIENTS: The authors studied 31 patients (aged 34 +/
      7 years; 21 women) with relapsing-remitting MS during 3 years of IFN beta-1b
      treatment. Systematic thyroid assessment was performed every 3 or 6 months,
      depending on the development of thyroid disease. RESULTS: After the first year of
      IFN beta-1b treatment, no further cases of thyroid disease were observed. Among
      the six patients with early incident subclinical hypothyroidism, thyroid
      dysfunction persisted only in those with baseline autoimmune thyroiditis (n = 2).
      The three patients who developed transient hyperthyroidism remained euthyroid
      throughout the treatment course. A positive autoantibody titer was continually
      detected in only two out of five patients without baseline autoimmunity.
      CONCLUSIONS: The risk of thyroid disease seems related to IFN beta-1b treatment
      during the first year only, particularly in patients with preexisting
      thyroiditis. Furthermore, incident thyroid dysfunction is generally transient and
      mild in degree. Indeed, we recommend a routine systematic thyroid assessment only
      in patients with baseline thyroiditis. During the first year of therapy, serum
      thyroid-stimulating hormone measurement should suffice as first line test; a
      systematic thyroid assessment is only useful for those patients with incidental
      and persistent dysfunction. Further studies with many patients will be necessary
      to confirm our suggestions as broad clinical guidelines.

PMID- 10953191
TI  - Perineurium contributes to axonal damage in acute inflammatory demyelinating
      polyneuropathy.
AB  - OBJECTIVE: To assess if axonal damage in severe acute inflammatory demyelinating
      polyneuropathy (AIDP) correlates with the appearance of epiperineurium in nerve
      trunks. BACKGROUND: Increase of endoneurial fluid pressure in nerve trunks
      possessing epiperineurium may be an important mechanism of axonal damage in AIDP.
      METHODS: A 79-year-old man had a 2-day history of acroparesthesias and ascending
      paralysis culminating in quadriplegia, bilateral facial palsy, and mechanical
      ventilation. Five intravenous immunoglobulin cycles were given without response.
      He died on day 60. Electrophysiologic studies (days 4, 17, and 50) initially
      showed normal nerve conduction velocities with further slowing, progressive
      attenuation of compound muscle action potentials, and profuse denervation. The
      authors studied the preforaminal anterior and posterior L3 and L5 spinal roots,
      third and fifth lumbar nerves and their branches, and femoral and sural nerves.
      RESULTS: Density of myelinated fibers was preserved in L5 ventral and dorsal
      roots and reduced in sural nerve. Mild de-remyelination was observed in lumbar
      roots. In both lumbar nerves and their branches, there were extensive de
      remyelination and centrofascicular or wedge-shaped areas with marked loss of
      large myelinated fibers. Axonal degeneration was the predominant lesion in sural
      nerve. CONCLUSION: The presence of epiperineurium correlates with a drastic
      change of pathology with superimposed ischemic lesions and distally accentuated
      axonal loss, suggesting that endoneurial fluid pressure increase could cause
      axonal damage in AIDP.

PMID- 10953192
TI  - Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne
      dystrophy.
AB  - BACKGROUND: Mental retardation is a clinical feature of Duchenne dystrophy (DD)
      and affects about one-third of patients. No clear association has been found
      between DNA mutations, protein expression, and IQ scores, although distal
      deletions in the dystrophin gene have been reported in association with
      intellectual impairment. A role for the brain distal dystrophin isoform Dp140 was
      suggested. OBJECTIVE: To explore the possible association between cognitive
      impairment and DNA macrodeletions in the distal part of the gene, including Dp140
      gene region. METHODS: Sixty-six patients with DD received general intelligence
      assessment by Wechsler Intelligence Scales measuring full, verbal, and
      performance IQ. PCR analysis was performed to detect deletions in the dystrophin
      gene, and the Dp140 regulatory region was analyzed in a subgroup of 12 patients.
      Statistical analysis was performed by nonparametric Wilcoxon rank signed and rank
      sum tests. RESULTS: Comparison of neuropsychological and genetic data revealed an
      association between distal macrodeletions and cognitive impairment (p < 0.001).
      Comparing deletions involving the Dp140 gene region with deletions presumably not
      altering Dp140 expression resulted in even greater significance. CONCLUSIONS:
      These data suggest that in DD, distal dystrophin deletions are associated with
      intellectual impairment. This study highlights a possible role for the brain
      distal isoform Dp140 in normal cognitive development.

PMID- 10953193
TI  - Neuroimages: amusement park stroke.

PMID- 10953195
TI  - Late-onset SCA2: 33 CAG repeats are sufficient to cause disease.
AB  - SCA-2 is an autosomal dominant inherited disorder characterized by ataxia, slow
      saccades, and hyporeflexia. The authors evaluated a patient with a mild balance
      problem with a SCA-2 allele sized at 33 CAG repeats. The authors then ascertained
      her 91 year-old mother, who showed disease onset at age 86 with an SCA-2 allele
      of identical size. Their study indicates that 33 CAG repeats can be pathogenic at
      the SCA-2 locus, though such an allele may produce an extremely late onset and
      gradual rate of disease progression.

PMID- 10953194
TI  - Transplantation of cultured human neuronal cells for patients with stroke.
AB  - Transplantation of cultured neuronal cells is safe in animal models and improves
      motor and cognitive deficits in rats with stroke. The authors studied the safety
      and feasibility of human neuronal cellular transplantation in patients with basal
      ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75
      years) with an infarct 6 months to 6 years previously (stable for at least 2
      months). Serial evaluations (12 to 18 months) showed no adverse cell-related
      serologic or imaging-defined effects. The total European Stroke Scale score
      improved in six patients (3 to 10 points), with a mean improvement 2.9 points in
      all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved
      fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is
      feasible in patients with motor infarction.

PMID- 10953196
TI  - False pituitary tumor in CSF leaks.
AB  - The authors describe five patients with typical clinical and MRI features of CSF
      leak and large enhancing pituitaries. The source of CSF leak was identified and
      surgically repaired in three patients. This was followed by disappearance of
      clinical symptoms and resolution of MRI abnormalities, including the pituitary
      enlargement. Enhancing enlargement of pituitary is another head MRI abnormality
      in CSF leaks, likely reflecting a secondary pituitary hyperemia.

PMID- 10953197
TI  - Three-year survival and functional outcome of patients with idiopathic adult
      hydrocephalus syndrome.
AB  - The functional outcome of 42 patients with idiopathic adult hydrocephalus
      syndrome (IAHS) was followed over a 3-year period after shunting. Survival curves
      were compared with those of age-matched healthy elderly subjects and patients
      with first-ever ischemic stroke. Twenty-seven patients with IAHS were improved 3
      months after the operation and 11 remained improved at the 3-year follow-up. The
      case fatality in patients with stroke and those with IAHS was similar (32% versus
      28%), but the relative risk of death among IAHS patients compared to a general
      elderly population was 3.3.

PMID- 10953198
TI  - Phenotype-genotype correlation in eight patients with Finnish variant late
      infantile NCL (CLN5).
AB  - The authors analyzed the clinical phenotype, including MRI, of eight patients
      with Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCLFin;
      CLN5; MIM256731). Although the four known mutations, including one novel mutation
      identified in this study, have very different consequences for the predicted
      polypeptide, none of them results in an atypical phenotype, as has been reported
      in other forms of NCL. Thus, it seems likely that each mutation severely disturbs
      the normal function of the CLN5 protein.

PMID- 10953199
TI  - Acute bilateral cerebellar infarcts in the territory of posterior inferior
      cerebellar artery.
AB  - The authors report 12 patients with acute bilateral cerebellar infarcts in
      posterior inferior cerebellar artery (PICA) territory. They found three
      topographic patterns: A) bilateral medial PICA in six patients; B) unilateral
      whole + contralateral medial PICA in four; and C) bilateral small multiple in
      two. Nine patients in Groups A and B had unilateral PICA or vertebral artery
      disease, and both patients in Group C had bilateral vertebral artery disease.
      These findings support that unilateral supply to both medial PICA territories may
      be the most relevant pathogenesis of this syndrome.

PMID- 10953200
TI  - Anti-GM1 antibody facilitates leakage in an in vitro blood-nerve barrier model.
AB  - Using an in vitro blood-nerve barrier (BNB) model, the authors tested the effect
      of various monoclonal antiganglioside antibodies on BNB function. Only anti-GM1
      antibody significantly facilitated BNB leakage in a concentration-dependent,
      complement-independent manner. This study provided evidence that anti-GM1
      antibody, frequently detected in sera from patients with inflammatory
      neuropathies, may participate BNB dysfunction and contribute to development of
      neuropathy.

PMID- 10953201
TI  - Adding valproate to lamotrigine: a study of their pharmacokinetic interaction.
AB  - The addition of valproic acid (VPA) to a lamotrigine monotherapy regimen (LTG)
      results in a decrement of LTG clearance. Whether this effect is related to the
      dose or concentration at steady state (Css) of VPA is yet to be established. This
      study was conducted to determine whether the dose or Css of VPA were inversely
      related to LTG clearance in 28 patients with intractable epilepsy who were
      treated with a combination of LTG and VPA. Correlations between LTG clearance and
      the dose and Css of VPA and comparisons of LTG clearance during low and high
      doses of VPA demonstrated that the degree of inhibition of LTG clearance is
      independent of the dose and Css of VPA.

PMID- 10953202
TI  - Postanoxic parkinsonism: clinical, radiologic, and pathologic correlation.
AB  - The authors report a 72-year-old patient who presented with parkinsonism after
      hypoxic-ischemic insult. T1-weighted MRI revealed high signal intensity lesions
      in the basal ganglia. Pathologic study of the brain disclosed multiple foci of
      old infarcts with gliosis and lipid-laden and hemosiderin-laden macrophages,
      indicating a previous minor hemorrhage after infarction. This observation
      provided pathologic correlation with the patient's clinical symptoms and MRI.

PMID- 10953203
TI  - Polymorphism at codon 129 of the prion protein gene is not associated with
      sporadic AD.
AB  - An association between cognitive performance in elderly people and variability in
      the codon 129 of the prion protein gene (PRNP) has been recently described. The
      authors analyzed this polymorphism in 278 sporadic AD patients and 268
      cognitively normal control subjects. Analyses stratifying by APOE genotype, age,
      and gender failed to reveal any association between homozygosity for the 129 PRNP
      methionine or valine alleles and AD.

PMID- 10953204
TI  - Proprioception more impaired distally than proximally in subjects with
      hemispheric dysfunction.
AB  - Holmes noted that with hemispheric injuries proprioceptive disturbances were more
      marked in the distal than proximal limb segments and proposed that this
      difference was related to the size of cortical sensory representations. An
      alternative hypothesis is that sensation from distal segments projects to the
      contralateral hemisphere and sensation from proximal segments projects to both
      hemispheres. Selective hemispheric anesthesia was used to test these alternative
      hypotheses and revealed a decrement in distal but not proximal proprioception
      with hemispheric anesthesia, thereby supporting the bilateral projection
      hypothesis.

PMID- 10953205
TI  - Movement disorders secondary to adulterated medication.

PMID- 10953206
TI  - Orolingual angioneurotic edema following therapy of acute ischemic stroke with
      alteplase.

PMID- 10953207
TI  - Psychosis and progressing dementia: presenting features of a mitochondriopathy.

PMID- 10953208
TI  - Neuroimages: cerebrotendinous xanthomatosis.

PMID- 10953209
TI  - Parkinsonism due to predominant involvement of substantia nigra in Japanese
      encephalitis.

PMID- 10953210
TI  - Neurology and psychiatry: closing the great divide.

PMID- 10953211
TI  - Loss of ability to sneeze in lateral medullary syndrome.

PMID- 10953212
TI  - Positive CSF HSV PCR in patients with GBM: a note of caution.

PMID- 10953213
TI  - Differentiation of vascular dementia from AD on neuropsychological tests.

PMID- 10953214
TI  - Valproate-induced hyperammonemic encephalopathy in the presence of topiramate.

PMID- 10953215
TI  - Botulinum toxin A as treatment for drooling saliva in PD.

PMID- 10953216
TI  - Analysis of excretory-secretory and somatic antigens of Gastrothylax crumenifer.
AB  - The excretory/secretory (ES) metabolic products released by Gastrothylax
      crumenifer (Trematoda: Digenea) during in vitro incubations and the somatic
      extract of the adult parasite were analysed using polyacrylamide gel
      electrophoresis (PAGE). Immunogenicity of ES and somatic extracts were evaluated
      by immunoblotting and ELISA using sera raised against ES and somatic antigens in
      rabbits. The electropherograms of ES and somatic extracts have been resolved into
      38 and 41 polypeptides, respectively. The apparent molecular weights of these
      polypeptides range from < 29 to > 205 kDa. A total of 14 polypeptides were found
      to be common to both of the samples. The analysis of immunoblot results revealed
      22 and 27 antigenic polypeptides in ES and somatic extracts respectively. Only 11
      and 13 antigenic polypeptides were found specific to ES and tissue extract
      respectively. The molecular weights of these specific polypeptides were
      calculated to be < 14.4, 16, 20, 25, 33, 42, 119, 125 and > 205 kDa for metabolic
      products and < 14.4, 25, 30, 35, 78, 84 and > 205 kDa for the tissue extracts,
      respectively. Analysis of ELISA results revealed that a dilution of up to 1:3200
      of the test sera could react with the ES product. Further, when the ES antigens
      were allowed to react with antisomatic extracts in hyperimmune sera the titre of
      IgG increased up to a dilution of 1:12800. The potential importance of these
      antigens in the immunodiagnosis of amphistomiasis is discussed.

PMID- 10953217
TI  - A field study of natural infections in three freshwater snails with Fasciola
      hepatica and/or Paramphistomum daubneyi in central France.
AB  - Natural infections of three freshwater snails with Fasciola hepatica and/or
      Paramphistomum daubneyi were studied during two periods in 1996 and 1997 (June
      July and September-October) on 18 farms located in the departments of Vienne and
      Haute Vienne (central France), and known for low prevalences of F. hepatica
      infections in ruminants. A total of 1573 Lymnaea glabra and 1421 L. truncatula 6
      mm high or more were collected in the meadows of 13 farms and dissected under
      laboratory conditions. Snails with single or concurrent infections of F. hepatica
      and/or

PMID- 10953218
TI  - Genomic variability within laboratory and wild isolates of the trichostrongyle
      mouse nematode Heligmosomoides polygyrus.
AB  - PCR-RFLP techniques have been used to characterize wild and laboratory isolates
      of the trichostrongyle nematode Heligmosomoides polygyrus from the wood mouse
      Apodemus sylvaticus and the laboratory mouse Mus musculus respectively. Both
      isolates can be distinguished by eight endonuclease digestions of the ITS region
      of the rDNA repeat namely, Alu I, Dde I, Hpa II, Hae III, Hinf I, Hha I, Pvu II
      and Sal I. In two of the digests, Hinf I and Rsa I, a minor polymorphism was
      observed in the wild isolate of H. polygyrus which has been cultured in
      laboratory-bred A. sylvaticus for several generations when compared with H. p.
      polygyrus from wild A. sylvaticus. A minor polymorphism was also identified in
      further wild isolates of H. polygyrus collected from A. sylvaticus in a field
      site in Egham, Surrey. However no evidence of polymorphism was observed in the
      laboratory isolate of H. polygyrus from the CD1 strain of M. musculus and the
      laboratory-bred A. sylvaticus. Reasons for this are discussed and further studies
      on the population genetics of H. polygyrus are suggested.

PMID- 10953219
TI  - In vitro interactions between epithelial cells and Gyrodactylus derjavini.
AB  - Skin responses of fish to various parasites have been shown to involve various
      immunologically competent cells producing factors which guide the reactions of
      epithelial cells. However, the present study has demonstrated that a monoculture
      of epithelial cells has the ability to encapsulate and partially degrade
      ectoparasites without involvement of leukocytes. The ectoparasitic
      monogeneanGyrodactylus derjavini was kept on a monolayer of Epithelioma Papulosum
      Cyprini (EPC) cells in 24-well multidishes supplied with tissue culture medium.
      Gyrodactylus derjavini did not reproduce but survived an incubation period of up
      to139h in the system. Due to sterile conditions, dead gyrodactylids were not
      subjected to microbial degradation and remained intact for several weeks.
      However, at 40 days G. derjavini was overgrown by EPC-cells and became partly
      degraded during the following 15 days. Analysis of enzyme reactivity in EPC-cells
      showed reactions for ten enzymes including esterases, amidases, phosphatases and
      phosphohydrolases. No marked differences for the ten enzymes between cell
      cultures with and without the ectoparasites were found but it cannot be excluded
      that some of these enzymes took part in parasite degradation. The study showed
      the in vitro capability of epithelial cells to interact, encapsulate and degrade
      G. derjavini without the involvement of leukocytes. This response probably is non
      specific and will not exclude that various immunocompetent cells and their
      products normally optimize and accelerate elimination of invading parasites in
      vivo.

PMID- 10953220
TI  - Changes in hepatic lipids of mice infected with cysticerci of Taenia crassiceps.
AB  - Nuclear magnetic resonance (NMR) spectroscopy was employed to investigate the
      effect of infection with Taenia crassiceps cysticerci on the lipid profile of
      mouse liver. Chloroform/methanol extracts of livers from infected mice showed
      lower concentrations of phosphatidylethanolamine, phosphatidylcholine,
      phosphatidylinositol, total glycerophospholipid, triacylglycerol, total fatty
      acid (FA) and all measured FA components than those from controls. Furthermore,
      the ratios obtained on dividing concentrations of the FA components by that of
      total FA demonstrate that the concentration decreases caused by infection are
      less for polyunsaturated fatty acids (FAs) than for other FAs. Extracts of T.
      crassiceps displayed a similar lipid profile to that of host liver but contained
      a lower lipid content and a shorter average FA chain length.

PMID- 10953221
TI  - Comparison of IgG3 responses to carbohydrates following mouse infection or
      immunization with six species of Trichinella.
AB  - The IgG3 antibody responses to carbohydrate epitopes were compared in BALB/c mice
      infected or immunized with six species of Trichinella: T. spiralis (T1), T.
      nativa (T2), T. britovi (T3), T6, T. nelsoni (T7), and T8. The dynamics of IgG3
      responses and antigen recognition following infection or immunization were
      measured by ELISA and Western blot respectively, using glycosylated and
      deglycosylated larval crude extracts (LCE) prepared from homologous isolates. A
      high degree of protein glycosylation was found in all species and with similar
      profiles. Deglycosylation was completely achieved only in LCE from T1 and T6
      isolates. The dynamics of IgG3 responses following infection or immunization
      significantly differed whereas the antigen recognition profiles appeared similar.
      Variations in the levels and antigen recognition patterns of IgG3 among the
      different species were apparent. The highest IgG3 levels were recorded in
      infections by the T8 isolate and the lowest in infections by the T6 isolate,
      whereas for immunization the highest IgG3 response was induced by T7 and the
      lowest by T8. Following antigen deglycosylation, the IgG3 responses were
      significantly reduced or abrogated and the recognition patterns markedly modified
      or suppressed in the different species of Trichinella.

PMID- 10953222
TI  - The intensity and duration of primary Heligmosomoides polygyrusinfection in TO
      mice modify acquired immunity to secondary challenge.
AB  - The effect of dose and duration of immunizing infections of Heligmosomoides
      polygyrus on protection against homologous challenge was studied in female TO
      mice. Primary infections were terminated at various levels with pyrantel embonate
      (adult infections) or ivermectin (larval infections) and mice were then
      challenged with 500 infective larvae (L3). The level of protection to secondary
      challenge positively correlated with the intensity of the primary immunizing
      infection but truncation of larval infection produced significantly better
      protection than termination of the adult nematode infection. The duration of the
      primary larval infection (1-6 days) positively correlated with the level of
      protection to secondary challenge, antibody responses and the proportion of
      circulating eosinophils. Histological changes in the gastrointestinal tract,
      peripheral leucocytic changes and antibody responses of the mice to H. polygyrus
      adult somatic antigens indicate both a cellular and humoral basis of host
      immunity to secondary challenge. Although the TO mice are slow responders in that
      they harbour chronic infections, immunization by intramucosal killing of the
      larval stage produced strong protection against secondary challenge infection.
      The presence of dead immunogenic larval stages within the intestinal wall may
      well be an important factor, since it exposes the host to stage specific antigens
      at an appropriate location. The implications of the findings for the control of
      gastrointestinal nematode infections are also discussed.

PMID- 10953223
TI  - Immune responses of the argasid tick Ornithodoros moubata moubata induced by
      infection with the filarial worm Acanthocheilonema viteae.
AB  - Investigations were undertaken to determine whether the tick Ornithodoros moubata
      moubata mounted a detectable immune response to primary and secondary infections
      with Acanthocheilonema viteae. Uninfected control tick survival rate was 70%, but
      only 45% in the primary infection group. Post-secondary infection survival rate
      (82%) was comparable to controls, indicating that these selected ticks had some
      protective advantage. Mean A. viteae infective larvae recovery from ticks with
      secondary infections was 31.4% lower than expected, suggesting the development of
      immunity. SDS-PAGE of haemolymph for proteins induced post-primary infection
      yielded a stronger signal at 45 kDa than controls, which was further elevated
      post-secondary infection. Proteins at 48, 22 and 16 to 18 kDa were detected in
      haemolymph from infected ticks but not seen from controls. The direct effect of
      haemolymph on microfilarial viability was examined using a novel in vitro assay;
      in these preliminary trials no differences were observed in parasite viability
      when exposed to haemolymph from infected or uninfected groups of ticks.

PMID- 10953224
TI  - In vitro antifilarial activity of extracts of the medicinal plant Cardiospermum
      halicacabum against Brugia pahangi.
AB  - The in vitro effects of ethanol and aqueous extracts of the medicinal plant
      Cardiospermum halicacabum on adult worms and microfilariae of Brugia pahangi were
      investigated. With or without the plant extracts in culture medium, the motility
      of adult worms, microfilariae and microfilarial release from female worms were
      monitored daily. After 7 days of culture, viability or tissue damage of adult
      worms was assessed using the MTT assay. At > 500 microg ml-1, the aqueous extract
      significantly reduced motility of adult females after 24 h of exposure and adult
      males after 3 days. The aqueous extract, at > 500 microg ml-1, also significantly
      reduced microfilarial release from female worms, starting on day 2. The reduction
      in the motility of adult worms and the pattern of microfilarial release from
      female worms were concentration and time dependent. The MTT assay results
      revealed that adult worms cultured in the presence of aqueous extracts at > 500
      microg ml-1 were damaged. However, the aqueous extract did not affect the
      motility of microfilariae with the exception of those in higher concentration
      extracts. Higher concentrations of ethanol extracts (2 mg ml-1) inhibited both
      the motility of adult worms and the release of microfilariae from females. Little
      effect of ethanol extracts was detected by the MTT assay, as only slight damage
      was caused to worms exposed only to the highest concentration (2 mg ml-1).
      However, ethanol extract at 500 microg ml-1 rapidly reduced the motility of
      microfilariae on day 2. The present study revealed that an aqueous extract of C.
      halicacabum has mild but definite direct macrofilaricidal action on B. pahangi.

PMID- 10953225
TI  - Strongyloides ratti: chemotactic responses of third-stage larvae to selected
      serum proteins and albumins.
AB  - Experiments were carried out in vitro to investigate whether the sera of several
      animals as well as albumins and peptides might act as attractants for larvae of
      Strongyloides ratti. Samples of sera from several mammal species were dialysed
      and the aliquots were further centrifuged using ultrafiltration cartridges to
      remove any remaining small molecules. Additional test substances included
      commercially obtained ovalbumin, rat and bovine serum albumins, polypeptides such
      as peptone, tryptone and tryptose, amino nitrogens, monosaccharides, and reduced
      glutathione (triaminopeptide). Larvae were strongly attracted to the dialysed
      mammalian sera, which mainly consisted of serum albumin and globulins. Ov- and
      serum albumins, and polypeptides also acted as attractants. On the other hand,
      reduced glutathione, 16 kinds of amino acids and four kinds of monosaccharides
      did not attract this nematode.

PMID- 10953226
TI  - Effects of Bothriocephalus acheilognathi on the polarization response of
      pronephric leucocytes of carp, Cyprinus carpio.
AB  - An in vitro assay was used to examine the effect of Bothriocephalus acheilognathi
      Yamaguti, 1934 (Cestoda: Pseudophyllidea) on the polarization response of
      pronephric leucocytes of carp, Cyprinus carpio. Leucocytes, isolated from naive,
      naturally-infected fish and carp injected intraperitoneally with cestode
      extracts, were exposed to parasite extracts (protein concentrations 0-10.0 microg
      ml-1), for up to 24 h in the presence or absence of carp serum. In general,
      polarization responses of the pronephric leucocytes, primarily neutrophils and
      eosinophils, increased with incubation time although there was no significant
      difference in the response induced by the different protein concentrations.
      Differences in the polarization response were, however, observed in naive,
      naturally infected and injected fish and the cells responded differently in the
      presence and absence of carp serum. In the absence of carp serum the polarization
      response of pronephric leucocytes in vitro was significantly reduced with cells
      obtained from injected and naturally infected fish compared with those obtained
      from naive carp. This suppression of leucocyte migration was however reduced by
      the addition of carp serum to the in vitro system. The role of this interaction
      between the possible suppression of polarization induced by the parasite and
      stimulation by serum is discussed.

PMID- 10953227
TI  - Allometric growth of the proglottids and strobila of the tapeworm, Hymenolepis
      diminuta.
AB  - HYMENOLEPIS DIMINUTA: adults were killed and fixed in fully extended positions,
      and the total lengths of the strobilae, numbers of proglottids, and distances of
      proglottids along the strobilae were determined. The relationship of proglottid
      number to distance along the strobila was exponential. Beginning at proglottid
      100 (P100), the lengths and widths of proglottids at 100 proglottid intervals
      were determined, and the surfaces areas were calculated. The relationships of
      proglottid length and width to proglottid number were linear, but the
      relationship of proglottid number to surface area (SA) was exponential. The
      volumes of proglottids were calculated, and the relationship of volume (V) to
      proglottid number was exponential. The relationship of surface area to volume
      ratio (SAVR) to proglottid number was exponential; at the anterior end of the
      worm (P100), the SAVR was 14.6, while at the posterior end of the worm (P1300)
      the ratio was 4.2. A single exponential equation describing the relationships
      among proglottid number, SA, and V was derived.

PMID- 10953229
TI  - Genetic diversity among isolates of Trichinella spiralis from the Province of
      Buenos Aires, Argentina.
AB  - Random Amplified Polymorphic DNAs, (RAPDs) are used to study the occurrence of
      Trichinella britovi and T5 among domestic animals in the Province of Buenos
      Aires, Argentina and to assess the genetic diversity among isolates of T.
      spiralisfrom this area in a number of infected hosts. All the local isolates
      proved to be T. spiralis. Six of the eight primers used indicate that the Buenos
      Aires isolates are distinct from each other as they produce a considerable number
      of polymorphic bands. Our overall estimates are relatively higher than other
      intraspecific distances previously estimated within species of this genus and
      among T. spiralis isolates. Such high degrees of variability observed among local
      isolates and between isolates from Buenos Aires and Spain should be taken into
      account when defining isolates within this species, and considering differences
      in the epidemiology of T. spiralis.

PMID- 10953228
TI  - Congenital transmission of Schistosoma japonicum in the rabbit.
AB  - Fourteen pregnant rabbits were each infected with 300 cercariae of Schistosoma
      japonicum and divided into two groups. Group M (n = 8) was infected during mid
      gestation (the organogenetic stage) and group L (n = 6) was infected during late
      gestation (the post-organogenetic stage). Mother rabbits and rabbit kittens were
      killed 45-60 days after infection and perfused in order to obtain worm counts.
      Furthermore, faecal egg counts and tissue egg counts from livers were obtained
      from the mother rabbits as well as the rabbit kittens. All mother rabbits became
      infected harbouring 207.6 +/- 20.2 and 220.0 +/- 27.5 adult worms in group M and
      L, respectively. In groups M and L, 13.5% and 46.7% of the kittens were infected,
      respectively. In 12 of 14 litters at least one kitten was infected. The infected
      kittens harboured between one and three adult S. japonicum. The livers of the
      kittens infected with a worm pair displaced lesions as a result of egg
      deposition. The results, therefore, show that congenital transmission of S.
      japonicumcan occur in rabbits. The close anatomical resemblance between the
      rabbit and human placenta may be indicative of the presence of congenital
      transmission of S. japonicum infection in humans.

PMID- 10953230
TI  - Preface

PMID- 10953231
TI  - I. The neurocognitive profile of Williams Syndrome: a complex pattern of
      strengths and weaknesses.
AB  - The rare, genetically based disorder, Williams syndrome (WMS), produces a
      constellation of distinctive cognitive, neuroanatomical, and electrophysiological
      features which we explore through the series of studies reported here. In this
      paper, we focus primarily on the cognitive characteristics of WMS and begin to
      forge links among these characteristics, the brain, and the genetic basis of the
      disorder. The distinctive cognitive profile of individuals with WMS includes
      relative strengths in language and facial processing and profound impairment in
      spatial cognition. The cognitive profile of abilities, including what is
      'typical' for individuals with WMS is discussed, but we also highlight areas of
      variability across the group of individuals with WMS that we have studied.
      Although the overall cognitive abilities (IQs) of individuals with WMS are
      typically in the mild-to-moderate range of mental retardation, the peaks and
      valleys within different cognitive domains make this syndrome especially
      intriguing to study across levels. Understanding the brain basis (and ultimately
      the genetic basis) for higher cognitive functioning is the goal we have begun to
      undertake with this line of interdisciplinary research.

PMID- 10953232
TI  - II. Hypersociability in Williams Syndrome.
AB  - Studies of abnormal populations provide a rare opportunity for examining
      relationships between cognition, genotype and brain neurobiology, permitting
      comparisons across these different levels of analysis. In our studies, we
      investigate individuals with a rare, genetically based disorder called Williams
      syndrome (WMS) to draw links among these levels. A critical component of such a
      cross-domain undertaking is the clear delineation of the phenotype of the
      disorder in question. Of special interest in this paper is a relatively
      unexplored unusual social phenotype in WMS that includes an overfriendly and
      engaging personality. Four studies measuring distinct aspects of hypersocial
      behavior in WMS are presented, each probing specific aspects in WMS infants,
      toddlers, school age children, and adults. The abnormal profile of excessively
      social behavior represents an important component of the phenotype that may
      distinguish WMS from other developmental disorders. Furthermore, the studies show
      that the profile is observed across a wide range of ages, and emerges
      consistently across multiple experimental paradigms. These studies of hypersocial
      behavior in WMS promise to provide the groundwork for crossdisciplinary analyses
      of gene-brain-behavior relationships.

PMID- 10953233
TI  - III. Electrophysiological studies of face processing in Williams syndrome.
AB  - Williams Syndrome (WMS) is a genetically based disorder characterized by
      pronounced variability in performance across different domains of cognitive
      functioning. This study examined brain activity linked to face-processing
      abilities, which are typically spared in individuals with WMS. Subjects watched
      photographic pairs of upright or inverted faces and indicated if the second face
      matched or did not match the first face. Results from a previous study with
      normal adults showed dramatic differences in the timing and distribution of ERP
      effects linked to recognition of upright and inverted faces. In normal adults,
      upright faces elicited ERP differences to matched vs. mismatched faces at
      approximately 320 msec (N320) after the onset of the second stimulus. This "N320"
      effect was largest over anterior regions of the right hemisphere. In contrast,
      the mismatch/match effect for inverted faces consisted of a large positive
      component between 400 and 1000 msec (P500) that was largest over parietal regions
      and was symmetrical. In contrast to normal adults, WMS subjects showed an N320
      mismatch effect for both upright and inverted faces. Additionally, the WMS
      subjects did not display the N320 right-hemisphere asymmetry observed in the
      normal adults. WMS subjects also displayed an abnormally small negativity at 100
      msec (N100) and an abnormally large negativity at 200 msec (N200) to both upright
      and inverted faces. This ERP pattern was observed in all subjects with WMS but
      was not observed in the normal controls. These results may be linked to increased
      attention to faces in subjects with WMS and might be specific to the disorder.
      These results were consistent with our ERP studies of language processing in WMS,
      which suggested abnormal cerebral specialization for spared cognitive functions
      in individuals with WMS.

PMID- 10953234
TI  - IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study.
AB  - Williams syndrome (WMS), a genetic condition resulting from a contiguous deletion
      on the long arm of chromosome 7, is associated with a relatively consistent
      profile of neurocognitive and neurobehavioral features. The distinctiveness and
      regularity of the profile of learning and behavioral characteristics in this
      genetic condition suggests that underlying neurobiological correlates may be
      identifiable. In this initial study, we report findings derived from a high
      resolution neuroimaging study of 14 young adult subjects with WMS and an
      individually matched normal control group. Compared to controls, subjects with
      WMS were noted to have decreased overall brain and cerebral volumes, relative
      preservation of cerebellar and superior temporal gyrus (STG) volumes, and
      disproportionate volume reduction of the brainstem. Analyses also suggested that
      the pattern of cerebral lobe proportions in WMS may be altered compared to normal
      controls with a greater ratio of frontal to posterior (parietal+occipital)
      tissue. Assessment of tissue composition indicated that, relative to controls,
      individuals with WMS have relative preservation of cerebral gray matter volume
      and disproportionate reduction in cerebral white matter volume. However, within
      the cerebral gray matter tissue compartment, the right occipital lobe was noted
      to have excess volume loss. Combined with our growing knowledge of the function
      of genes in the commonly deleted region for WMS, more detailed information
      regarding the structure and function of the WMS brain will provide a unique
      opportunity for elucidating meaningful correlations amongst genetic,
      neurobiological, and neurobehavioral factors in humans.

PMID- 10953235
TI  - V. Multi-level analysis of cortical neuroanatomy in Williams syndrome.
AB  - The purpose of a neuroanatomical analysis of Williams Syndrome (WMS) brains is to
      help bridge the knowledge of the genetics of this disorder with the knowledge on
      behavior. Here, we outline findings of cortical neuroanatomy at multiple levels.
      We describe the gross anatomy with respect to brain shape, cortical folding, and
      asymmetry. This, as with most neuroanatomical information available in the
      literature on anatomical-functional correlations, links up best to the behavioral
      profile. Then, we describe the cytoarchitectonic appearance of the cortex.
      Further, we report on some histometric results. Finally, we present findings of
      immunocytochemistry that attempt to link up to the genomic deletion. The gross
      anatomical findings consist mainly of a small brain that shows curtailment in the
      posterior-parietal and occipital regions. There is also subtle dysmorphism of
      cortical folding. A consistent finding is a short central sulcus that does not
      become opercularized in the interhemispheric fissure, bringing attention to a
      possible developmental anomaly affecting the dorsal half of the hemispheres.
      There is also lack of asymmetry in the planum temporale. The cortical
      cytoarchitecture is relatively normal, with all sampled areas showing features
      typical of the region from which they are taken. Measurements in area 17 show
      increased cell size and decreased cell-packing density, which address the issue
      of possible abnormal connectivity. Immunostaining shows absence of elastin but
      normal staining for Lim-1 kinase, both of which are products of genes that are
      part of the deletion. Finally, one serially sectioned brain shows a fair amount
      of acquired pathology of microvascular origin related most likely to underlying
      hypertension and heart disease.

PMID- 10953237
TI  - Neural systems as nonlinear filters.
AB  - Experimental data show that biological synapses behave quite differently from the
      symbolic synapses in all common artificial neural network models. Biological
      synapses are dynamic; their "weight" changes on a short timescale by several
      hundred percent in dependence of the past input to the synapse. In this article
      we address the question how this inherent synaptic dynamics (which should not be
      confused with long term learning) affects the computational power of a neural
      network. In particular, we analyze computations on temporal and spatiotemporal
      patterns, and we give a complete mathematical characterization of all filters
      that can be approximated by feedforward neural networks with dynamic synapses. It
      turns out that even with just a single hidden layer, such networks can
      approximate a very rich class of nonlinear filters: all filters that can be
      characterized by Volterra series. This result is robust with regard to various
      changes in the model for synaptic dynamics. Our characterization result provides
      for all nonlinear filters that are approximable by Volterra series a new
      complexity hierarchy related to the cost of implementing such filters in neural
      systems.

PMID- 10953236
TI  - VI. Genome structure and cognitive map of Williams syndrome.
AB  - Williams syndrome (WMS) is a most compelling model of human cognition, of human
      genome organization, and of evolution. Due to a deletion in chromosome band
      7q11.23, subjects have cardiovascular, connective tissue, and neurodevelopmental
      deficits. Given the striking peaks and valleys in neurocognition including
      deficits in visual-spatial and global processing, preserved language and face
      processing, hypersociability, and heightened affect, the goal of this work has
      been to identify the genes that are responsible, the cause of the deletion, and
      its origin in primate evolution. To do this, we have generated an integrated
      physical, genetic, and transcriptional map of the WMS and flanking regions using
      multicolor metaphase and interphase fluorescence in situ hybridization (FISH) of
      bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs), BAC
      end sequencing, PCR gene marker and microsatellite, large-scale sequencing, cDNA
      library, and database analyses. The results indicate the genomic organization of
      the WMS region as two nested duplicated regions flanking a largely single-copy
      region. There are at least two common deletion breakpoints, one in the
      centromeric and at least two in the telomeric repeated regions. Clones anchoring
      the unique to the repeated regions are defined along with three new pseudogene
      families. Primate studies indicate an evolutionary hot spot for chromosomal
      inversion in the WMS region. A cognitive phenotypic map of WMS is presented,
      which combines previous data with five further WMS subjects and three atypical
      WMS subjects with deletions; two larger (deleted for D7S489L) and one smaller,
      deleted for genes telomeric to FZD9, through LIMK1, but not WSCR1 or telomeric.
      The results establish regions and consequent gene candidates for WMS features
      including mental retardation, hypersociability, and facial features. The approach
      provides the basis for defining pathways linking genetic underpinnings with the
      neuroanatomical, functional, and behavioral consequences that result in human
      cognition.

PMID- 10953238
TI  - Analytical model for the effects of learning on spike count distributions.
AB  - The spike count distribution observed when recording from a variety of neurons in
      many different conditions has a fairly stereotypical shape, with a single mode at
      zero or close to a low average count, and a long, quasi-exponential tail to high
      counts. Such a distribution has been suggested to be the direct result of three
      simple facts: the firing frequency of a typical cortical neuron is close to
      linear in the summed input current entering the soma, above a threshold; the
      input current varies on several timescales, both faster and slower than the
      window used to count spikes; and the input distribution at any timescale can be
      taken to be approximately normal. The third assumption is violated by associative
      learning, which generates correlations between the synaptic weight vector on the
      dendritic tree of a neuron, and the input activity vectors it is repeatedly
      subject to. We show analytically that for a simple feed-forward model, the normal
      distribution of the slow components of the input current becomes the sum of two
      quasi-normal terms. The term important below threshold shifts with learning,
      while the term important above threshold does not shift but grows in width. These
      deviations from the standard distribution may be observable in appropriate
      recording experiments.

PMID- 10953239
TI  - Calculation of interspike intervals for integrate-and-fire neurons with poisson
      distribution of synaptic inputs.
AB  - We present a new technique for calculating the interspike intervals of integrate
      and-fire neurons. There are two new components to this technique. First, the
      probability density of the summed potential is calculated by integrating over the
      distribution of arrival times of the afferent post-synaptic potentials (PSPs),
      rather than using conventional stochastic differential equation techniques. A
      general formulation of this technique is given in terms of the probability
      distribution of the inputs and the time course of the postsynaptic response. The
      expressions are evaluated in the gaussian approximation, which gives results that
      become more accurate for large numbers of small-amplitude PSPs. Second, the
      probability density of output spikes, which are generated when the potential
      reaches threshold, is given in terms of an integral involving a conditional
      probability density. This expression is a generalization of the renewal equation,
      but it holds for both leaky neurons and situations in which there is no time
      translational invariance. The conditional probability density of the potential is
      calculated using the same technique of integrating over the distribution of
      arrival times of the afferent PSPs. For inputs with a Poisson distribution, the
      known analytic solutions for both the perfect integrator model and the Stein
      model (which incorporates membrane potential leakage) in the diffusion limit are
      obtained. The interspike interval distribution may also be calculated numerically
      for models that incorporate both membrane potential leakage and a finite rise
      time of the postsynaptic response. Plots of the relationship between input and
      output firing rates, as well as the coefficient of variation, are given, and
      inputs with varying rates and amplitudes, including inhibitory inputs, are
      analyzed. The results indicate that neurons functioning near their critical
      threshold, where the inputs are just sufficient to cause firing, display a large
      variability in their spike timings.

PMID- 10953240
TI  - Statistical procedures for spatiotemporal neuronal data with applications to
      optical recording of the auditory cortex.
AB  - This article presents new procedures for multisite spatiotemporal neuronal data
      analysis. A new statistical model - the diffusion model - is considered, whose
      parameters can be estimated from experimental data thanks to mean-field
      approximations. This work has been applied to optical recording of the guinea
      pig's auditory cortex (layers II-III). The rates of innovation and internal
      diffusion inside the stimulated area have been estimated. The results suggest
      that the activity of the layer balances between the alternate predominance of its
      innovation process and its internal process.

PMID- 10953241
TI  - Probabilistic motion estimation based on temporal coherence.
AB  - We develop a theory for the temporal integration of visual motion motivated by
      psychophysical experiments. The theory proposes that input data are temporally
      grouped and used to predict and estimate the motion flows in the image sequence.
      This temporal grouping can be considered a generalization of the data association
      techniques that engineers use to study motion sequences. Our temporal grouping
      theory is expressed in terms of the Bayesian generalization of standard Kalman
      filtering. To implement the theory, we derive a parallel network that shares some
      properties of cortical networks. Computer simulations of this network demonstrate
      that our theory qualitatively accounts for psychophysical experiments on motion
      occlusion and motion outliers. In deriving our theory, we assumed spatial
      factorizability of the probability distributions and made the approximation of
      updating the marginal distributions of velocity at each point. This allowed us to
      perform local computations and simplified our implementation. We argue that these
      approximations are suitable for the stimuli we are considering (for which spatial
      coherence effects are negligible).

PMID- 10953242
TI  - Boosting neural networks.
AB  - Boosting is a general method for improving the performance of learning
      algorithms. A recently proposed boosting algorithm, AdaBoost, has been applied
      with great success to several benchmark machine learning problems using mainly
      decision trees as base classifiers. In this article we investigate whether
      AdaBoost also works as well with neural networks, and we discuss the advantages
      and drawbacks of different versions of the AdaBoost algorithm. In particular, we
      compare training methods based on sampling the training set and weighting the
      cost function. The results suggest that random resampling of the training data is
      not the main explanation of the success of the improvements brought by AdaBoost.
      This is in contrast to bagging, which directly aims at reducing variance and for
      which random resampling is essential to obtain the reduction in generalization
      error. Our system achieves about 1.4% error on a data set of on-line handwritten
      digits from more than 200 writers. A boosted multilayer network achieved 1.5%
      error on the UCI letters and 8.1% error on the UCI satellite data set, which is
      significantly better than boosted decision trees.

PMID- 10953243
TI  - Gradient-based optimization of hyperparameters.
AB  - Many machine learning algorithms can be formulated as the minimization of a
      training criterion that involves a hyperparameter. This hyperparameter is usually
      chosen by trial and error with a model selection criterion. In this article we
      present a methodology to optimize several hyperparameters, based on the
      computation of the gradient of a model selection criterion with respect to the
      hyperparameters. In the case of a quadratic training criterion, the gradient of
      the selection criterion with respect to the hyperparameters is efficiently
      computed by backpropagating through a Cholesky decomposition. In the more general
      case, we show that the implicit function theorem can be used to derive a formula
      for the hyperparameter gradient involving second derivatives of the training
      criterion.

PMID- 10953244
TI  - A signal-flow-graph approach to on-line gradient calculation.
AB  - A large class of nonlinear dynamic adaptive systems such as dynamic recurrent
      neural networks can be effectively represented by signal flow graphs (SFGs). By
      this method, complex systems are described as a general connection of many simple
      components, each of them implementing a simple one-input, one-output
      transformation, as in an electrical circuit. Even if graph representations are
      popular in the neural network community, they are often used for qualitative
      description rather than for rigorous representation and computational purposes.
      In this article, a method for both on-line and batch-backward gradient
      computation of a system output or cost function with respect to system parameters
      is derived by the SFG representation theory and its known properties. The system
      can be any causal, in general nonlinear and time-variant, dynamic system
      represented by an SFG, in particular any feedforward, time-delay, or recurrent
      neural network. In this work, we use discrete-time notation, but the same theory
      holds for the continuous-time case. The gradient is obtained in a straightforward
      way by the analysis of two SFGs, the original one and its adjoint (obtained from
      the first by simple transformations), without the complex chain rule expansions
      of derivatives usually employed. This method can be used for sensitivity analysis
      and for learning both off-line and on-line. On-line learning is particularly
      important since it is required by many real applications, such as digital signal
      processing, system identification and control, channel equalization, and
      predistortion.

PMID- 10953245
TI  - Bootstrapping neural networks.
AB  - Knowledge about the distribution of a statistical estimator is important for
      various purposes, such as the construction of confidence intervals for model
      parameters or the determination of critical values of tests. A widely used method
      to estimate this distribution is the so-called boot-strap, which is based on an
      imitation of the probabilistic structure of the data-generating process on the
      basis of the information provided by a given set of random observations. In this
      article we investigate this classical method in the context of artificial neural
      networks used for estimating a mapping from input to output space. We establish
      consistency results for bootstrap estimates of the distribution of parameter
      estimates.

PMID- 10953246
TI  - Information geometry of mean-field approximation.
AB  - I present a general theory of mean-field approximation based on information
      geometry and applicable not only to Boltzmann machines but also to wider classes
      of statistical models. Using perturbation expansion of the Kullback divergence
      (or Plefka expansion in statistical physics), a formulation of mean-field
      approximation of general orders is derived. It includes in a natural way the
      "naive" mean-field approximation and is consistent with the Thouless-Anderson
      Palmer (TAP) approach and the linear response theorem in statistical physics.

PMID- 10953247
TI  - Measuring the VC-dimension using optimized experimental design.
AB  - VC-dimension is the measure of model complexity (capacity) used in VC-theory. The
      knowledge of the VC-dimension of an estimator is necessary for rigorous
      complexity control using analytic VC generalization bounds. Unfortunately, it is
      not possible to obtain the analytic estimates of the VC-dimension in most cases.
      Hence, a recent proposal is to measure the VC-dimension of an estimator
      experimentally by fitting the theoretical formula to a set of experimental
      measurements of the frequency of errors on artificially generated data sets of
      varying sizes (Vapnik, Levin, & Le Cun, 1994). However, it may be difficult to
      obtain an accurate estimate of the VC-dimension due to the variability of random
      samples in the experimental procedure proposed by Vapnik et al. (1994). We
      address this problem by proposing an improved design procedure for specifying the
      measurement points (i.e., the sample size and the number of repeated experiments
      at a given sample size). Our approach leads to a nonuniform design structure as
      opposed to the uniform design structure used in the original article (Vapnik et
      al., 1994). Our simulation results show that the proposed optimized design
      structure leads to a more accurate estimation of the VC-dimension using the
      experimental procedure. The results also show that a more accurate estimation of
      VC-dimension leads to improved complexity control using analytic VC
      generalization bounds and, hence, better prediction accuracy.

PMID- 10953248
TI  - Evolution of self-reproducing programs in a core propelled by parallel protein
      execution.
AB  - An evolutionary core memory system named SeMar is revised so that the entire
      action of the core might proceed by parallel execution of Proteins. The Proteins
      created by the transcription of DNA units work as operators and accomplish the
      corresponding instructions written in DNA units. In the experiment, it is shown
      that after inoculation of a man-made self-reproducing creature into the core, its
      offspring evolve through mutational modifications and the efficiency of the
      replication rate of DNA increases by the polyploidization of DNA sequences.

PMID- 10953249
TI  - A simple model of unbounded evolutionary versatility as a largest-scale trend in
      organismal evolution.
AB  - The idea that there are any large-scale trends in the evolution of biological
      organisms is highly controversial. It is commonly believed, for example, that
      there is a large-scale trend in evolution towards increasing complexity, but
      empirical and theoretical arguments undermine this belief. Natural selection
      results in organisms that are well adapted to their local environments, but it is
      not clear how local adaptation can produce a global trend. In this paper, I
      present a simple computational model, in which local adaptation to a randomly
      changing environment results in a global trend towards increasing evolutionary
      versatility. In this model, for evolutionary versatility to increase without
      bound, the environment must be highly dynamic. The model also shows that
      unbounded evolutionary versatility implies an accelerating evolutionary pace. I
      believe that unbounded increase in evolutionary versatility is a large-scale
      trend in evolution. I discuss some of the testable predictions about organismal
      evolution that are suggested by the model.

PMID- 10953250
TI  - Effects of compression on language evolution.
AB  - For many adaptive complex systems information about the environment is not simply
      recorded in a look-up table, but is rather encoded in a theory, schema, or model,
      which compresses information. The grammar of a language can be viewed as such a
      schema or theory. In a prior study [Teal et al., 1999] we proposed several
      conjectures about the learning and evolution of language that should follow from
      these observations: (C1) compression aids in generalization; (C2) compression
      occurs more easily in a "smooth," as opposed to a "rugged," problem space: and
      (C3) constraints from compression make it likely that natural languages evolve
      towards smooth string spaces. This previous work found general, if not complete
      support for these three conjectures. Here we build on that study to clarify the
      relationship between Minimum Description Length (MDL) and error in our model and
      examine evolution of certain languages in more detail. Our results suggest a
      fourth conjecture: that all else being equal, (C4) more complex languages change
      more rapidly during evolution.

PMID- 10953251
TI  - Artificial life: discipline or method? Report on a debate held at ECAL '99.

PMID- 10953252
TI  - Cooperative strategies and the evolution of communication.
AB  - Using communication is not the only cooperative strategy that can evolve when
      organisms need to solve a problem together. This article describes a model that
      extends MacLennan and Burghardt's [37] synthetic ethology simulation to show that
      using a spatial world in a simulation allows a wider range of strategies to
      evolve in response to environmental demands. The model specifically explores the
      interaction between population density and resource abundance and their effect on
      the kinds of cooperative strategies that evolve. Signaling strategies evolve
      except when population density is high or resource abundance is low.

PMID- 10953253
TI  - Commercialization of academia research.

PMID- 10953254
TI  - Human in vivo competitive inhibition of P450 substrates: increased plasma
      concentrations as a function of hepatic extraction ratio and percent inhibition.
AB  - The purpose of this note is to posit and discuss the concept of "competitive
      inhibition potential" (CIP), which is an in vivo index of the ability of a
      competitive inhibitor to elevate plasma concentrations of drug substrates, when
      the competitive inhibitor is administered at its usual and customary dose.

PMID- 10953255
TI  - Application of direct search optimization for pharmacokinetic parameter
      estimation.
AB  - PURPOSE: For simple pharmacokinetic compartmental models, analytical solution to
      the governing differential equations along with common graphical methods provide
      a mean to evaluate the associated rate constants. These graphical methods,
      however, can not be used for the more complex multi-compartment models.
      Furthermore, parameter estimation using slope and intercept values from the
      graphical methods is often accompanied with error. In this study a numerical
      solution is applied for the solution of the governing differential equations and
      a simple direct search optimization procedure utilizing random numbers is used
      for pharmacokinetic parameter estimation. METHOD: The methodology is demonstrated
      with reference to experimental literature data for ciprofloxacin and ofloxacin
      whose pharmacokinetic behavior has been reported in terms of a two-compartment
      model. RESULTS: Examination of the predicted drug concentrations from the
      graphical method and the optimization methodology indicate that both methods have
      comparable accuracy in predicting the drug concentrations. The graphical method,
      however, only shows good accuracy in the early stages both after i.v. and oral
      drug administration whereas the optimization procedure, due to the nature of the
      objective function formulation, provides good accuracy over the entire range of
      times after drug administration. CONCLUSIONS: The methodology is simple, provides
      optimized parameters which accurately predict drug concentrations, and is
      flexible to include more weight on the early-time data or be extended to multi
      compartment models.

PMID- 10953256
TI  - A novel skin penetration enhancer: evaluation by membrane diffusion and confocal
      microscopy.
AB  - PURPOSE: The aim of this study was to determine the in vitro transdermal efficacy
      of a Meyer Zall Laboratories (MZL) oil/water emulsion in two separate
      preparations containing the actives, coal tar and the non-steroidal anti
      inflammatory drug, diclofenac sodium. METHOD: The release rate of the two active
      ingredients from MZL dermatological preparations, Exorex and Athru-Derm and four
      comparator products was determined using an enhancer cell system, whilst specific
      penetration characteristics of the MZL formulation were elucidated using confocal
      and electron microscopy. The latter properties were explored at both the organ
      level, using human skin, as well as at a cellular level using a melanoma cell
      line. RESULTS: While the in vitro release rates for all formulations was high,
      coal tar and diclofenac release from Exorex and Athru-Derm respectively was, at
      nearly all time intervals, significantly higher than from comparator products.
      Microscopy revealed the presence of spherical liposomal type structures in both
      the MZL lotion and a comparator gel. In the MZL lotion, the majority of these
      structures, referred to here as emzaloid particles, were in the order of
      magnitude of about 50 nm to 1 microm in diameter with a small minority exceeding
      these dimensions. After application of Athru-Derm to human skin, intact emzaloid
      particles of submicron dimensions were detected in the epidermis in association
      with the cell membranes. The affinity of the MZL lotion for cell membranes was
      further demonstrated with melanoma cells; in addition, the formulation was seen
      to penetrate even to the nucleus of viable cells. CONCLUSION: Overall the data
      suggest that the oil/water base in MZL formulations is a highly efficient
      transdermal vehicle able to transport a wide range of indication- specific
      actives to their site of action.

PMID- 10953257
TI  - Antitumoral activity of new pyrimidine derivatives of sesquiterpene lactones.
AB  - Sesquiterpene lactones display a wide variety of biological effects such as
      antiviral, anti-inflammatory and cytotoxic activity. In previous studies some
      derivatives of sesquiterpene lactones were prepared to be tested as antiviral
      and/or cytoxic agents. In the present report we describe the effects of seven
      modified sesquiterpene lactones on the proliferation of several cancer cell
      lines. We demonstrated antitumoral activity of two of them: III (JLNZ-106) and IV
      (EDAG-IV-Sme) in HeLa, C-33, CALO, INBL, VIPA, SW480, SW620, MCF-7 and CHO cancer
      cell lines. Compounds III (JLNZ-106) and IV (EDAG-IV-Sme-IV) presented cytotoxic
      activity (IC50) by inhibiting the incorporation of (14)C-thymidine to DNA. These
      experiments suggest that derivatives III and IV should inhibit DNA replication in
      cancer cell lines.

PMID- 10953258
TI  - Are statins anti-inflammatory? Issues in the design and conduct of the
      pravastatin inflammation C-reactive protein evaluation.

PMID- 10953259
TI  - The role of C-reactive protein in cardiovascular disease risk.
AB  - Over the past few years, a flurry of data in the medical literature has strongly
      implicated C-reactive protein (CRP) as a marker of inflammation in coronary
      artery disease (CAD). Recognizing the likely integral role that inflammation
      plays in the pathogenesis of atherosclerosis, many hospital laboratories have
      tests to measure CRP concentration in the clinical setting. However, the clinical
      use of these tests still need definition. To date, of the plasma-based markers
      investigated, CRP provides the strongest risk prediction for cardiovascular
      disease in men and women. Questions remain regarding the degree to which CRP can
      improve risk stratification beyond that of the traditional risk factors of CAD.

PMID- 10953260
TI  - Weighing the evidence for infection as a risk factor for coronary heart disease.
AB  - There has been considerable attention in recent years to the intriguing
      hypothesis that coronary heart disease and other atherosclerotic diseases may be
      caused by infection with pathogens such as Chlamydia pneumoniae, Helicobacter
      pylori, and cytomegalovirus. Supporting this hypothesis are studies that localize
      bacterial antigens to atherosclerotic plaques and that draw associations of
      systemic inflammation and chronic infections with coronary disease. Although
      there are several examples of positive associations of pathogen seropositivity
      with disease, recent prospective follow-up studies of infection seropositivity
      have not generally supported these associations. At present, the evidence is
      insufficient to designate infection as a causal risk factor for coronary heart
      disease. The results of ongoing larger observational studies and antibiotic
      treatment trials may yield important information regarding the presence and
      magnitude of risk, if any, beyond that conferred by established coronary risk
      factors.

PMID- 10953261
TI  - Hormone replacement therapy and cardiovascular risk.
AB  - We are reexamining the role of hormone replacement therapy in cardiovascular risk
      in light of the results from the Heart and Estrogen/Progestin Replacement Study
      (HERS) trial. Prior to this trial, the wealth of evidence in the laboratory and
      in observational trials suggested that estrogen replacement was associated with
      significant cardioprotection. The HERS trial was the first randomized trial of
      this therapy in postmenopausal women with coronary artery disease, and it did not
      demonstrate a reduction in cardiovascular events in women taking hormone
      replacement therapy. These findings have made us rethink some of the basic
      science underlying the cardiovascular effects of hormone replacement therapy.
      Recent evidence regarding thromboembolic risk, inflammation, and types of hormone
      replacement therapy is discussed.

PMID- 10953262
TI  - Beta-carotene, vitamin C, and vitamin E and cardiovascular diseases.
AB  - Observational studies have shown an inverse relationship between consumption of
      fruits and vegetables high in beta-carotene, vitamins C and E, and ischemic heart
      disease (IHD) and stroke. In large observational studies, beta- carotene reduced
      the risk of IHD events in men, particularly in smokers. In contrast, four large
      randomized trials did not reveal a reduction in cardiovascular events with beta
      carotene use, and may, in fact, increase IHD and total mortality in male smokers.
      There have been only a few large observational studies and one randomized trial
      with vitamin C, which have shown no beneficial or deleterious impact of this
      vitamin on cardiovascular events. Most large observational studies have shown an
      inverse relationship between vitamin E and IHD. However, a meta-analysis of the
      four randomized trials done in Europe and America involving a total of 51,000
      participants allocated to vitamin E or placebo for 1.4 to 6 years, did not
      demonstrate a reduction in cardiovascular and IHD mortality and nonfatal
      myocardial infarction. Currently, there are no data to support the use of these
      vitamins to reduce the risk of cardiovascular events. Trials are in progress to
      determine whether a longer duration of administration of vitamin E or the
      association of vitamin E with cofactors may reduce cardiovascular events.

PMID- 10953264
TI  - Prophylactic defibrillator implantation in patients with coronary artery disease.

PMID- 10953265
TI  - Management of atrial flutter.
AB  - Typical atrial flutter is a macroreentrant arrhythmia of the right atrium. The
      isthmus area between the tricuspid annulus, the inferior vena cava, and the
      ostium of the coronary sinus is a critical zone of the reentry circle. Atrial
      flutter has been treated with class I and III antiarrhytmic drugs to maintain
      sinus rhythm, with moderate success. Catheter ablation has been highly successful
      in treating atrial flutter. A contiguous line of bidirectional electrical block
      is created in the isthmus area between the tricuspid annulus and the inferior
      vena cava by application of radiofrequency energy. In patients with both atrial
      flutter and atrial fibrillation, ablation of the atrial flutter circuit may make
      the atrial fibrillation more easy to control. Quality of life assessments show
      improvement after ablation of atrial flutter. With a probability of success of
      90%, a recurrence rate of 5% to 15%, and few complications, catheter ablation
      emerges as the best treatment of recurrent, symptomatic flutter.

PMID- 10953263
TI  - Imaging techniques to predict cardiovascular risk.
AB  - Conventional cardiovascular imaging, with a focus on identifying flow-limiting
      stenoses, does not directly image the atherosclerotic lesion. Recent clinical and
      pathobiologic data indicate that stenosis severity does not dictate
      cardiovascular risk and that there are functional, structural, and biologic
      features of atherosclerosis that are associated with cardiovascular events.
      Imaging technologies, such as ultrasound, light, x-ray, magnetic resonance, and
      targeted contrast agents, have been developed to characterize directly the
      atherosclerotic vessel wall. They provide promising approaches to predict
      cardiovascular risk and facilitate further study of the mechanisms of
      atherosclerosis progression and its response to therapy.

PMID- 10953266
TI  - Radiofrequency catheter ablation of atrial fibrillation initiated by spontaneous
      ectopic beats.
AB  - Several reports have demonstrated that most paroxysmal atrial fibrillation is
      initiated by ectopic beats from a focal area, and radiofrequency catheter
      ablation can effectively cure atrial fibrillation. Although most of the ectopic
      beats originate from the orifices of the pulmonary veins or from the myocardial
      sleeves in the pulmonary veins, ectopic beats can also originate from superior
      vena cava, crista terminalis, coronary sinus, ligament of Marshall, or left
      atrial posterior free wall. Owing to the potential risk and complexity of
      catheter ablation, the ideal candidates should have frequent episodes and drug
      refractory paroxysmal atrial fibrillation.

PMID- 10953267
TI  - The utility of intracardiac echocardiography in interventional electrophysiology.
AB  - With the mounting of an ultrasound transducer on the end of a percutaneously
      placed catheter, intracardiac echocardiography is now possible. It has become
      clear that endocardial anatomy plays a critical role in a variety of cardiac
      arrhythmias. The ability to visualize this anatomy, and it's relationship to
      mapping and ablation catheters, may greatly enhance the safety and efficacy of
      catheter ablation procedures.

PMID- 10953269
TI  - Are implantable cardioverter- defibrillators cost-effective?
AB  - Sudden cardiac deaths account for a large number of cardiovascular deaths, and
      ventricular tachyarrhythmias are implicated in many of these. In survivors of
      sudden cardiac deaths and other selected groups of patients, implantable
      cardioverter-defibrillators (ICDs) have been shown to have significant survival
      benefits in randomized controlled trials. The incremental costs for each extra
      year of survival conferred by ICDs were compared to the cost of antiarrhythmic
      drug therapy in some of these trials. In patients with nonsustained ventricular
      tachycardia with low ejection fraction (< 35%) and inducible sustained
      ventricular tachycardia on programmed electrical stimulation (nonsuppressible by
      procainamide), the incremental costs of ICD therapy amounted to $27,000 per life
      year saved, compared with drug therapy. These costs may be acceptable increments
      for adaptation of the new technology in view of the definite survival advantage
      conferred by ICDs. Evolving technology may further reduce these costs by
      development of better devices with longer battery life.

PMID- 10953268
TI  - Implantable dual-chamber cardioverter-defibrillator-pacemaker.
AB  - The fifth generation of implantable cardioverter-defibrillators offer enhanced
      modes of detection of atrial and ventricular arrhythmias, antitachycardia pacing
      and shocks, multiprogrammability, intracardiac electrogram storage, and all
      functions of antibradycardia dual-chamber pacing including rate responsiveness
      and mode switching. There is no consensus on the indications for dual-chamber
      pacemaker defibrillator systems. This review focuses on the four major options of
      newer devices that might benefit patients: 1) permanent dual-chamber pacing in
      ischemic coronary disease patients, 2) detection and management of atrial
      fibrillation or other atrial tachyarrhythmias, 3) some newer indications for
      pacing, and 4) the suppression of inappropriate interventions. On the basis of
      published data, newer indications for the dual-chamber systems, advantages and
      limitations, and future perspectives are discussed.

PMID- 10953270
TI  - Methods of minimizing inappropriate implantable cardioverter-defibrillator
      shocks.
AB  - As more and more patients receive complex implantable cardioverter-defibrillators
      (ICDs), profound knowledge about the incidence of inappropriate device therapy,
      the reasons it happens, and the possibilities for prevention is crucial. In this
      article, the most important prevention algorithms incorporated in current ICD
      models and their advantages and handicaps are discussed in detail, which should
      help to guide the device selection for a particular patient. Also, emphasis is
      put on adjunctive drug therapy and interventional treatment strategies, which are
      crucial in managing patients with inappropriate ICD shocks.

PMID- 10953272
TI  - The debate over chronic pain continues

PMID- 10953271
TI  - Emerging indications for permanent pacing.
AB  - New indications for pacing are being investigated in the areas of vasovagal
      syncope, hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy, and
      atrial fibrillation. It is hoped that pacing will offer an alternative therapy to
      patients who are refractory to medical therapy. Although pacing for vasovagal
      syncope continues to be controversial, it appears that a highly symptomatic group
      with a predominately cardioinhibitory component can benefit. Current data
      indicate that dual-chamber pacing should not be considered therapeutically equal
      to septal myectomy in patients with hypertrophic obstructive cardiomyopathy, but
      may be considered in those more than 65 years of age, or in others who are not
      good surgical candidates. Biventricular or left ventricular pacing appears
      promising in heart failure patients and may be combined with implantable
      cardioverter-defibrillator therapy. Lead technology for coronary vein placement
      needs further improvement. Dual-site atrial pacing appears to help prevent
      recurrences of atrial fibrillation and may become a useful adjunct to drug,
      ablative, and implantable cardioverter-defibrillator therapies.

PMID- 10953273
TI  - Controversies surrounding reflex sympathetic dystrophy: a review article.
AB  - The topic of reflex sympathetic dystrophy (RSD) has generated an increasingly
      significant volume of medical literature and controversy over the last decade. A
      search of PubMed, the online site of the National Library of Medicine, for papers
      on RSD reveals nearly 2200 articles on the topic (using algodystrophy as the
      search word, wherein RSD references are also included, and more older and
      European articles are also listed). From 1991 through 1998 inclusive there is an
      average of nearly 100 articles per year on the topic, which represents more than
      a third of all the articles referenced since 1965. In the decade of the 1980s,
      there is an average of 64 articles per year, 74 per year in the last half of the
      decade and 54 per year in the first half. Prior to the decade of the 1980s, one
      finds an average of 40 articles per year back to the mid-1960s. The controversy
      surrounding the disorder centers around the nature of the problem and whether it
      is a primary organic disorder or a primary psychogenic disorder associated with
      the accomplishment of some secondary gain. If it is the former, then clearly
      research should continue to determine the nature and etiology of the
      malfunctioning organ(s). If, on the other hand, RSD is a psychogenic disorder,
      then the medical community does well to focus mainly on the peripheral
      manifestations of the problem. In that instance, therapy should be primarily
      psychological and cognitive with regard to the secondary gain, and persistent
      organic treatments are unlikely to improve the condition in general and worsen
      individual cases.

PMID- 10953274
TI  - Reflex sympathetic dystrophy: a sympathetically mediated pain syndrome or not?
AB  - Because of the controversy concerning the manner in which the sympathetic nervous
      system is involved in reflex sympathetic dystrophy (RSD), its name was changed to
      one having no mechanistic connotations. This article reviews the relevant
      literature in support of not only the taxonomical changes to complex regional
      pain syndrome (CRPS) but also provides evidence of sympathetic dysfunction
      demonstrated in animal models of neuropathic pain.

PMID- 10953275
TI  - Psychological determinants of fibromyalgia and related syndromes.
AB  - Fibromyalgia and other chronic pain and fatigue syndromes constitute an
      increasingly greater societal burden that currently is not being approached
      effectively by traditional Western medicine. Although the hallmarks of
      fibromyalgia--chronic widespread pain, fatigue, and multiple other somatic
      symptoms--have neurophysiologic and endocrinologic underpinnings, these
      biological aspects derive primarily from psychological variables. Female gender,
      adverse experiences during childhood, psychological vulnerability to stress, and
      a stressful, often frightening environment and culture are important antecedents
      of fibromyalgia. To understand fibromyalgia and related syndromes and to provide
      optimum care requires a biopsychosocial, not a biomedical, viewpoint.

PMID- 10953276
TI  - Is fibromyalgia a distinct clinical syndrome?
AB  - The validity of the fibromyalgia syndrome (FMS) as a distinct clinical entity has
      been challenged for several reasons. Many skeptics express concern about the
      subjective nature of chronic pain, the subjectivity of the tender point (TeP)
      examination, the lack of a gold standard laboratory test, and the absence of a
      clear pathogenic mechanism by which to define FMS. Another expressed concern has
      been the relative nature of the pain-distress relationship in the rheumatology
      clinic. The apparently continuous relationship between TePs and somatic distress
      across a variety of clinical disorders is said to argue against FMS as a separate
      clinical disorder. The most aggressive challenges of the FMS concept have been
      from legal defenses of insurance carriers motivated by economic concerns. Other
      forms of critique have presented as psychiatric dogma, uninformed posturing,
      suspicion of malingering, ignorance of nociceptive physiology, and occasionally
      have resulted from honest misunderstanding. It is not likely that a few
      paragraphs of data and logic will cause an unbeliever to change an ingrained
      opinion. Therefore, this review describes the clinical manifestations of FMS,
      responds to some of the theoretic arguments against it, and discusses some
      possible pathophysiologic mechanisms by which FMS may develop and persist as a
      unique syndrome.

PMID- 10953277
TI  - Fibromyalgia following trauma: psychology or biology?
AB  - The concept that fibromyalgia may follow trauma is currently an area of intense
      debate within the medical field and is driven to a large extent by social and
      legal issues. This article questions whether the current literature supports the
      notion that trauma may cause fibromyalgia and explores the relative contribution
      of biology and psychology in the development of and sense of disability from
      fibromyalgia.

PMID- 10953279
TI  - Are pain disorder and somatization disorder valid diagnostic entities?
AB  - Physicians and other clinicians who treat patients with chronic pain have
      doubtless recognized the interplay of various psychological and somatic variables
      in their patients' pain. Notwithstanding, there continues to be primary emphasis
      on the somatic factors, and continued neglect of the psychological. This article
      asserts that pain disorder and somatization disorder are indeed valid diagnostic
      entities, and that their respective incidence and prevalence are quite high both
      in patients with chronic pain and in the primary care setting. These diagnoses
      are compared and contrasted, along with the related diagnosis of the
      psychological factors affecting physical condition. Guidelines for assessment of
      these conditions are provided, as are recommendations as to when to refer
      patients for further psychological and psychiatric assessment and treatment.

PMID- 10953278
TI  - Is lumbar discography a determinate of discogenic low back pain: provocative
      discography reconsidered.
AB  - Provocative lumbar discography was investigated in a series of clinical studies
      at the Stanford University of Medicine, Stanford, CA. This work demonstrated that
      pain intensity during disc injection is strongly influenced by the subject's
      emotional and psychological profiles, chronic pain behavior, and ongoing
      compensation claims whether the patient has any back pain illness or not. Pain
      reproduction was also primarily related to penetration of the dye through the
      outer annulus and could not reliably be used to confirm the location of the pain
      source.

PMID- 10953280
TI  - Is the term "pain disorder" a valid diagnosis?
AB  - Although the feeling or sensation that we call pain is usually uncomfortable and
      unpleasant, it is actually a great asset in many situations in general medicine,
      especially when we think of children and older people. Were it not for a
      persistent complaint or expression of pain, family members or others might not
      realize that a small child or older person has suffered a significant injury or
      is ill. Indeed, at any age, the symptom of pain may be an important indication
      that a disease may be present. For young children, the sensation of pain can also
      be a learning experience, teaching them to take extra care with such items as hot
      stoves or broken glass. All those situations in which injury, disease, or
      something of a physical nature has caused pain are universally understood without
      any disagreement. We see in them a logical sequence of cause and effect. The
      focus of this article is on those patients who complain of pain for a long period
      of time but in whom no physical disease has ever been found.

PMID- 10953281
TI  - Epidemic occupational pseudo-illness: the plague of acronyms.
AB  - Genuine disorder caused by repetitive movement has unmistakable features vitally
      different from occupational pseudo-illness, which comes and goes in new guises
      and massive epidemics wherever the label legitimizes gain from compensation. The
      assumption of an existing label such as the carpal tunnel syndrome gives the
      false idea of greater potential for deception. The solution to the menace lies in
      logical reasoning, which recognizes falsity before it begins to dominate the
      minds of the community.

PMID- 10953282
TI  - Oxidative stress contributes to the anti-proliferative effects of flavone acetic
      acid on endothelial cells.
AB  - The synthetic flavonoid flavone acetic acid (FAA) has anti-tumor activity against
      a variety of transplanted tumors in mice through mechanisms which likely involve
      effects on tumor vasculature and the host immune system. The aims of the present
      in vitro study were to compare the sensitivity of tumor and endothelial cells to
      FAA treatment and to assess if nitric oxide and superoxide are involved in the
      FAA-mediated suppression of cell proliferation. FAA at 1 mM concentration was
      approximately two times more effective in suppressing proliferation of
      endothelial than tumor cells. The anti-proliferative effect of 1 mM FAA on
      endothelial cells was partially blocked by inhibitors to various superoxide
      producing enzymes (xanthine oxidase, cyclooxygenase, poly-ADP-ribose polymerase,
      ribonucleotide reductase) and completely inhibited by the direct scavengers of
      superoxide lucigenin and Tiron. In contrast, inhibitors of nitric oxide were
      unable to prevent the effects of FAA on proliferation. FAA induced apoptosis of
      endothelial cells, which was not affected by inhibitors of nitric oxide or
      superoxide. Our data imply that FAA inhibits proliferation of endothelial cells
      by a superoxide-dependent mechanism and induces apoptosis by a nitric oxide and
      superoxide-independent mechanism.

PMID- 10953283
TI  - Transcriptional profiling of human mammary carcinoma cell lines reveals PKW, a
      new tumor-specific gene.
AB  - In order to identify genes associated with distinct stages of mammary carcinoma
      we have investigated the transcriptional profile of normal mammary gland
      epithelial cells, cell lines derived from primary tumors, from bone marrow
      micrometastases and from ascites fluid. mRNA's for ribosomal protein L41 and URIM
      (Up-Regulated In Metastasis) were consistently increased in all cells derived
      from metastatic lesions. mRNA for human secreted frizzled-related protein (hsFRP)
      was found to be dramatically down-regulated in all mammary tumor cells compared
      to non-transformed mammary gland epithelial cells. mRNA for Human Hypoxia Related
      Factor--2 (HRF-2) and a transcript including the human mitochondrial control
      region were significantly overexpressed in the cell lines derived from primary
      tumors and ascites fluid. A new gene, referred to as PKW, was only expressed in
      one of the primary tumor cell lines, the one derived from a medullary carcinoma.
      The small and the large transcript which are derived by differential splicing
      encode potential proteins comprising 95 aa and 130 aa, sharing 88 aa at the N
      terminus. The IEP's suggest a nuclear localization of the proteins. Surprisingly
      mRNA for the new gene was detected only in the salivary gland, but not in other
      adult human tissues and a restricted panel of embryonic tissues. The same holds
      true for a panel of human tumor cell lines and cell lines derived from ductal
      mammary carcinoma. RT-PCR revealed expression of PKW in 4 out of 11 breast
      carcinomas.

PMID- 10953284
TI  - Time-dependent dephosphorylation through serine/threonine phosphatases is
      required for stable adhesion of highly and poorly metastatic HT-29 colon
      carcinoma cell lines to collagen.
AB  - Adhesion stabilization is a prerequisite for the long-term adhesion of
      circulating metastatic tumor cells, and tumor cells with different metastatic
      potential demonstrate distinct patterns of cell adhesion properties. An important
      event during formation of organ metastases is integrin-mediated extracellular
      matrix (ECM) binding that can initiate signal transduction events. Recently we
      reported that Ser/Thr kinases are involved in regulation of tumor cell adhesion.
      In the present study the influence of dephosphorylation by Ser/Thr protein
      phosphatases (PPases) on tumor cell adhesion was investigated. Pretreatment of
      poorly and highly metastatic human HT-29 colon carcinoma cells with the broad
      range inhibitors sodium fluoride (NaF) and sodium pyrophosphate (PyroP) resulted
      in strong reduction in adhesion of HT-29 cells to various ECM components.
      Surprisingly, when specific Ser/Thr PPase inhibitors like tautomycin were used we
      found only a partial reduction in adhesion of highly metastatic HT-29LMM cells to
      collagen I but not to collagen IV. Other inhibitors did not inhibit adhesion, and
      poorly metastatic HT-29P were not affected by any specific Ser/Thr PPase
      inhibitors. Therefore, the effects of NaF on adhesion-mediated Tyr
      phosphorylation were investigated further. Pretreatment with this inhibitor led
      to a reduction in phosphorylation of focal adhesion kinase (FAK). In contrast, in
      cells grown adherent to tissue culture dishes, low concentrations of NaF
      increased FAK phosphorylation whereas high concentrations inhibited the amount of
      phosphorylated FAK. Although NaF inhibited adhesions it did not cause changes in
      cell morphology or detachment of cells from ECM. We hypothesize that dual
      specific PPases may be involved in the regulation and establishment of new
      adhesive interactions in HT-29 cells, but they are not required for maintenance
      of stable adhesions to ECM.

PMID- 10953285
TI  - Differential response of normal, premalignant and malignant human oral epithelial
      cells to growth inhibition by chemopreventive agents.
AB  - Squamous cell carcinoma (SCC) of the oral cavity is a multistep process,
      progressing through a series of discrete, irreversible and complementary
      alterations in genes that control cell growth, death, and differentiation. In the
      premalignant state, the oral mucosa progresses through various grades of
      epithelial dysplasia, with the potential to convert to SCC. Chemopreventive
      strategies are designed to suppress, reverse, or prevent the formation of
      premalignant lesions and their subsequent progression to SCC. In the present
      study, we determined the growth inhibitory effect of 21 chemopreventive agents in
      a cell culture model using normal, premalignant, and malignant human oral mucosal
      cell lines. There were significant differences in the growth inhibitory responses
      of these cell lines to selected retinoids and non-retinoid analogs. Among the
      retinoids tested, the synthetic retinamides, as a class, showed selective growth
      inhibition of both premalignant and malignant cells compared to normal human oral
      epithelial cells in culture. Within the retinamide class, 2CPR exhibited the
      greatest selectivity in the growth inhibition of premalignant and malignant
      cells. Among the non-retinoids analyzed, DFMO was a moderate to potent inhibitor
      of malignant and premalignant oral cell growth, respectively, and stimulated
      normal oral cell growth at low concentrations. Using this in vitro approach, we
      have identified several potential chemopreventive agents for oral cancer as
      selective growth inhibitors of premalignant ahd malignant human oral mucosa
      cells.

PMID- 10953286
TI  - Longitudinal analysis of mammary cancer multiplicity in chemoprevention studies.
AB  - BACKGROUND: The effect of chemopreventive agents on cancer multiplicity is of
      primary interest in animal studies. The nature of data collected from
      chemoprevention studies may be analyzed by a longitudinal analysis of repeatedly
      measured cancer multiplicity data. METHODS: We determined the number of mammary
      cancers over the entire follow-up period for varying doses of two chemopreventive
      agents. Longitudinal analyses were performed to model the number of cancers over
      different time intervals. RESULTS: There was a significant increase in the number
      of cancers between six to seven weeks post-carcinogen administration in the
      control group. Varying patterns of cancer development were observed at different
      doses of chemopreventive agents including a delay in onset of tumor growth
      compared to the control group. CONCLUSION: Longitudinal data analysis complements
      traditional analyses by providing detailed information regarding the effect of
      chemopreventive agents on the pattern of tumor development throughout the follow
      up period. Importantly, some chemopreventive agents may delay time to appearance
      of mammary cancers without causing a significant difference in cancer
      multiplicity.

PMID- 10953287
TI  - Comparison of three approaches to doxorubicin therapy: free doxorubicin,
      liposomal doxorubicin, and beta-glucuronidase-activated prodrug (HMR 1826).
AB  - BACKGROUND: Three approaches to doxorubicin therapy are directly compared: free
      doxorubicin, liposomal doxorubicin and beta-glucuronidase-activated prodrug (HMR
      1826). MATERIALS AND METHODS: The optimal dose of HMR 1826 was determined to be
      200 mg/kg once a week and subsequent studies were carried out comparing HMR 1826
      at 200 mg/kg 1x/wk, liposomal doxorubicin (Doxil) at 9 mg/kg 1x/wk and free
      doxorubicin at 7 mg/kg 1x/wk in seven different human tumor xenograft models.
      RESULTS: All three forms of doxorubicin inhibited tumor growth with similar
      efficacy in each of the tumor models with the exception of MDA-MB-231 tumor
      xenografts, which were resistant to free doxorubicin but sensitive to Doxil and
      HMR 1826. Overall less weight loss was observed with HMR 1826 treatment.
      CONCLUSIONS: The efficacy of HMR 1826 is equal to or better than that of
      doxorubicin and Doxil at a safe dose and schedule, indicating that the beta
      glucuronidase activated prodrug approach is safe and effective.

PMID- 10953288
TI  - How can tumor cells escape intercellular induction of apoptosis?
AB  - A novel concept for the control of oncogenesis has been established for
      fibroblasts. Transformed fibroblasts are subject to intercellular induction of
      apoptosis by TGF-beta or FGF-triggered nontransformed neighboring cells. If this
      control system acts in vivo as efficiently as it does in vitro, tumor formation
      should require the establishment of resistance mechanisms directed against
      intercellular induction of apoptosis. In line with this hypothesis, ex vivo tumor
      cells have been recently shown to be resistant to intercellular induction of
      apoptosis, whereas cells transformed in vitro and not passaged in an organism
      were regularly sensitive. Based on the knowledge of signaling between transformed
      and nontransformed cells during intercellular induction of apoptosis, several
      possible mechanisms for resistance of tumor cells are summarized in this paper.

PMID- 10953289
TI  - The influence of different varieties of olive oil on N-methylnitrosourea(NMU)
      induced mammary tumorigenesis.
AB  - Several epidemiological and animal model studies suggest that consumption of
      olive oil, which is rich in the monounsaturated fatty acid, oleic acid (OA, C18:,
      n-9) may reduce the risk of breast cancer. There are however, a wide variety of
      olive oils in the marketplace with levels of OA ranging from a low of 50% to a
      high of 80% OA. The purpose of this rodent model study was to determine whether
      the level of OA in olive oil is a key determinant of its protective effects. We
      compared the inhibitory effects among three different types of olive oil
      containing 54, 70 and 80% OA and 20, 15 and 5% linoleic acid (LA), respectively,
      corn oil and a store bought olive oil, using the NMU-induced rat mammary tumor
      model. While little difference was found in total mammary tumor yields, a
      differential effect was found in the histological type of tumors formed. Olive
      oil containing 80% OA and 5% LA exhibited the lowest level of adenocarcinomas and
      the highest level of the more benign adenocarcinoma arising from within a
      fibroadenoma. While the reasons for this effect remain to be clarified, these
      results suggest that future studies on the health benefits of olive oil should
      take into account the type as well as the amount of olive oil.

PMID- 10953290
TI  - Immunohistochemical study of cyclooxygenases in prostatic adenocarcinoma;
      relationship to apoptosis and Bcl-2 protein expression.
AB  - BACKGROUND: Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic
      acid to prostaglandins and other eicosanoids. A recent report has indicated a
      selective COX-2 inhibitor resulted in increased apoptosis and down-regulated bcl
      2 expression in the androgen-sensitive human prostate cancer cell. We
      investigated the localization of COXs in prostatic adenocarcinoma and the
      possible correlation of androgen blockade with its expression. MATERIALS AND
      METHODS: The immunohistochemical expression of COX-1, COX-2 and bcl-2 protein was
      studied using paraffin-embedded archival tissues both before and after hormonal
      therapy. The number of apoptotic cells was also determined. RESULTS:
      Immunohistochemistry for COX-1, not COX-2, showed the constitutive expression in
      the stroma of normal prostate. The expression of COX-2 protein was detected less
      often than that of COX-1 protein in most cases of prostatic adenocarcinoma before
      hormonal therapy. Neoadjuvant hormonal therapy induced the expression of COX-2
      protein in smooth muscle cells, fibroblasts and adenocarcinoma cells. The
      expression after hormonal therapy was possibly correlated with the bcl-2 protein
      expression. CONCLUSION: The present study is the first to demonstrate the
      immunohistochemical expression of COXs in human prostate tissue and indicated
      that COXs were relevant to homeostasis and tumor development of the prostate.

PMID- 10953291
TI  - Human milk fat globule antigen 1 (HMFG1) expression in prostatic carcinoma and
      immunotargeting with a radiolabelled monoclonal anti-HMFG1 antibody.
AB  - BACKGROUND: Prostatic cancer is the leading cause of death in Swedish men.
      Approximately 50% have disseminated disease at diagnosis. Radiolabelled
      antibodies could possibly be a treatment modality for disseminated prostatic
      cancer, so that in this study the expression of the human milk fat globulin 1
      (HMFG1) antigen in prostate cancer was examined. MATERIALS AND METHODS: An
      immunohistochemistry technique with a murine monoclonal antibody was used, as
      well as the human prostate cancer cell line DU-145, which expresses this cell
      surface antigen. TUR specimens from patients with prostate cancer were also
      examined. RESULTS: Eighteen out of 22 (82%) patients exhibited an HMFG1-positive
      tumour. An inhomogenity in the immunostaining could occasionally be seen, with
      smaller apparently negative areas. The immunolocalisation properties of the
      antibody were investigated using a radiolabelled antibody injection into nude
      mice bearing heterotransplants of the DU-145 cell line. The highest accumulation
      of the antibody was seen in the tumour tissue and the liver. CONCLUSION: The
      results obtained form a basis for further investigations with the goal of using
      the antibodies for staging and therapy for prostate cancer.

PMID- 10953292
TI  - Tryptophan hydroxylase and 5-hydroxytryptamine in carcinoids of the
      gastrointestinal tract.
AB  - BACKGROUND: Tryptophan hydroxylase is the enzyme that catalyzes the formation of
      5-hydroxy-L-tryptophan which is the initial and rate-limiting enzyme in the
      biosynthesis of 5-hydroxytryptamine (serotonin). The aim of this study was to
      analyze the differential expression of tryptophan hydroxylase and 5
      hydroxytryptamine in human gastrointestinal carcinoids. MATERIAL AND METHODS:
      Primary carcinoids and hepatic carcinoid metastases (n = 8) were investigated for
      the presence of tryptophan hydroxylase, 5-hydroxytryptamine and chromogranin A.
      RESULTS: Only one of the tumors examined was immunoreactive for tryptophan
      hydroxylase, as determined by immunohistochemical techniques and Western blot
      analysis. All carcinoids expressed 5-hydroxytryptamine and chromogranin A.
      CONCLUSIONS: Carcinoids appear to be a heterogeneous group with respect to the
      expression of this monooxygenase. Based on these results it is proposed that
      other cells of the intestine are involved in the biosynthesis of 5
      hydroxytryptamine precursors taken up by carcinoid tumor cells.

PMID- 10953293
TI  - Molecular targets of guanine nucleotides in differentiation, proliferation and
      apoptosis.
AB  - Guanine nucleotides are important substrates for macromolecular synthesis, cell
      signaling, and integration of metabolic status, and have an evolutionarily
      conserved role in differentiation, proliferation, and apoptosis. Bacteria, yeast,
      and mammalian cells are all dependent on an adequate supply of guanylates to
      maintain proliferation. Depletion of intracellular guanylates, especially by
      inhibition of de novo synthesis via the IMP dehydrogenase pathway, is a potent
      signal for inhibition of proliferation, as well as apoptosis. Growth inhibition
      by depletion of GTP is a conserved pathway from humans to Bacillus. IMPDH
      expression is downregulated by the p53 tumor suppressor gene. Many inhibitors of
      IMP dehydrogenase are used as clinical agents. These agents are antivirals
      (ribavirin), antitumor (tiazofurin [TR], selenazofurin [SR], and benzamide
      riboside [BR]), and immunosuppressants (mycophenolic acid [MPA]). The biochemical
      actions of IMP dehydrogenase inhibitors are well known, but correlation with in
      vivo activities is difficult because the extent of exogenous contributions to the
      nucleotide metabolic pathways is not fully known. IMPDH inhibitors are
      biochemically convenient in inhibiting parallel pathways, since excess reactants
      IMP and 5'-phospho-ribose-1'-pyrophosphate (PRPP) inhibit guanine salvage
      synthesis. IMPDH activity is a progression-linked key enzyme in tumorigenesis.
      The antitumor potential of IMPDH inhibitors is therefore particularly high.

PMID- 10953294
TI  - Selective uptake by cancer cells of liposomes coated with polysaccharides bearing
      1-aminolactose.
AB  - We investigated the selective uptake of liposomes chemically modified by
      polysaccharides-cholesterol derivatives with 1-aminolactose (lactose) in two
      human hepatoma cell lines (HUH7 and Alexander), a human colon cancer cell line
      (FCC) and a human lung cancer cell line (KNS). The uptakes of the labeled
      liposomes alone (conventional liposomes), those with cholesterol pullulan (CHP)
      and with lactose (lactose CHP) were compared in four cancer cells and normal rat
      hepatocytes after 3 hours of incubation. The radioactivities of the lactose CHP
      were 4.4, 4, 3.4 and 4.4 times greater than those of CHP in HuH7, Alexander, FCC
      and KNS cells, respectively, after 3 hours of incubation. All the above
      differences were statistically significant (p < 0.01). No statistically
      significant differences were seen in the case of hepatocytes. Thus, cancer cells
      have a common affinity with lactose CHP liposomes, however, these mechanisms
      appear to have no connection with the galactose-specific asialoglycoprotein
      receptors of hepatocytes.

PMID- 10953295
TI  - Antitumor activity of mono- and dimetallic transition metal carborane complexes
      of Ta, Fe, Co, Mo, or W.
AB  - Complexes containing Ta, Fe, Co, Mo, or W metal centers that are bound to C2B4 or
      C2B3 small carborane ligands proved to be potent cytotoxic agents in murine and
      human tissue cultured cells, being more effective in suspended leukemia and
      lymphomas but surprisingly also effective against the growth of selected solid
      tumors. These complexes inhibited nucleic acid metabolism, specifically DNA and
      purine de novo syntheses. Key enzyme activities in nucleic acid metabolism which
      were inhibited by the complexes were P388 DNA polymerase a, ribonucleotide
      reductase, dihyrofolate reductase, PRRP-amidotransferase and IMP dehydrogenase.
      The complexes afforded a moderate amount of DNA-fragmentation in P388 lymhocytic
      leukemia cells and were moderate inhibitors of human DNA topoisomerase II
      activity; however, the DNA molecule itself was not a target of the complexes in
      that there was no evidence that the complexes caused intercalation between base
      pairs, caused cross-linking of the strands of DNA or alkylated the bases of DNA.

PMID- 10953296
TI  - Role of carbohydrate moiety in granulocyte colony stimulating factor.
AB  - Biological activities of two granulocyte-colony stimulating factor (G-CSF)
      preparations with (Lenograstim) or without (Filgrastim) sugar moiety were
      compared. Both G-CSF preparations similarly enhanced the N-Formyl-Met-Leu-Phe
      induced-migration of human peripheral blood polymorphonuclear cells, but did not
      significantly affect the proliferation of human oral tumor cell lines (HSC-2,
      HSG). However, Lenograstim induced cytotoxicity (accompanied by the production of
      cytoplasmic vacuoles and large DNA fragments) in human promyelocytic leukemic
      cells HL-60, more potently than Filgrastim. Lenograstim, but not Filgrastim,
      enhanced the cytotoxic activity of sodium ascorbate. In contrast to Lenograstim,
      Filgrastim was degraded gradually, but too slowly to explain its lower biological
      activity. These data suggest that the carbohydrate moiety in G-CSF might confer
      unique biological activities.

PMID- 10953297
TI  - Ex vivo tumor cell lines are resistant to intercellular induction of apoptosis
      and independent of exogenous survival factors.
AB  - Elimination of transformed fibroblasts through intercellular induction of
      apoptosis has been postulated as representing an efficient control step during
      oncogenesis. Whereas fibroblasts transformed by chemical carcinogens in vitro
      were sensitive to intercellular induction of apoptosis, ex vivo tumour cells
      derived from animals treated with chemical carcinogens were resistant to this
      control step. Resistance was achieved through two different mechanisms. Two cell
      lines overexpressed endogenous survival factors and thus the action of
      intercellular signalling (ICS) was not sufficient for complete depletion of
      endogenous survival factors. One of the resistant ex vivo tumour lines contained
      the same concentration of endogenous survival factors as its in vitro transformed
      and sensitive counterpart, but the endogenous survival factors were protected
      from the action of ICS in the resistant tumour cell line. In addition, the ex
      vivo tumour cell lines showed a marked independence of exogenous survival
      factors. Our data indicate that tumour formation requires independence of control
      by neighbouring cells and by exogenous survival factors.

PMID- 10953298
TI  - Growth hormone gene expression in normal lymph nodes and lymphomas of the dog.
AB  - Growth hormone (GH) is involved in the development, maturation, and function of
      the immune system. Recent studies have demonstrated that GH can be synthesized
      and secreted by lymphoid tissues, where it may act as an autocrine/paracrine
      growth factor. To determine whether GH may be involved in the development of
      hematological malignancies, GH gene expression in canine lymphomas was
      investigated. GH mRNA was detected in non-tumorous lymph nodes and in the
      majority of the lymphomas, by RT-PCR analysis. In situ and Northern blot
      hybridizations were negative. Analysis of the transcriptional start sites of the
      GH gene using 5'-RACE (rapid amplification of cDNA ends) showed that the canine
      lymphoid transcripts contained a 33-85 bp enlarged 5'-untranslated region
      compared to the pituitary and mammary GH transcripts. Part of the lymphoid GH
      transcripts contained intron 1, which would result in early termination of the
      translation due to an in-frame stopcodon. GH measurements in lymphoid tissues
      revealed a low content of immunoreactive GH. The results presented demonstrate
      that canine lymphoid tissue is an extrapituitary site of GH gene expression.
      However, GH production appeared to be low, indicating that lymphoid GH is
      probably not a major factor in the development or progression of canine lymphoma.

PMID- 10953299
TI  - Expression and purification of recombinant HIV-1 tat protein using HIV-1-tat
      specific monoclonal antibodies.
AB  - We expressed tat protein from HIV-1 coding AA 1-67 (strain HIV-Bru) in the
      inducible vector pTrc 99A in E. coli. The tat coding region was cloned in the ATG
      site of the expression vector. A sequence coding for 15 AA was added at the
      3'region as a molecular marker. After sonification, the tat protein was routinely
      detected in Western blots using the Mab developed by us. Following precipitation
      and centrifugation the resulting pellets were dissolved and purified by three
      different methods: 1. immunoaffinity-chromatography using Affi-gel HZ coupled
      with a Mab recognizing the N-terminal sequence of HIV-1-tat; 2. ion exchange
      chromatography using DEAE-52 cellulose, and 3. isoelectric focusing in free
      solution. The resulting protein extracts obtained from the three purification
      protocols were checked in ELISA with the antibody. The peak fraction from all the
      procedures showed tat activity. No cross reaction in the presence of sera from
      uninfected persons was observed. The results showed that the purification of tat
      protein using monoclonal antibodies leads to highly purified preparations.

PMID- 10953301
TI  - Cumulative results of chemosensitivity tests for antitumor agents in Japan. Japan
      Research Society for Appropriate Cancer Chemotherapy.
AB  - The Japan Research Society for Appropriate Cancer Chemotherapy set out to
      summarize the present status of chemosensitivity testing for antitumor agents in
      Japan. Two different questionnaires were sent to 122 and 94 institutes,
      respectively, whilst responses were received from 87 (71.3%) and 41 (43%)
      institutes, respectively. The results showed that chemosensitivity tests were
      performed in 42 institutes where a total of 2 in vivo and 10 in vitro different
      assays were performed. Actual cases of chemosensitivity detected by the tests
      varied from 1 to 368 cases/year/institute with a median of 15 cases and mean +/-
      standard deviation of 48 +/- 65 cases. The total number of tested cases increased
      from 1,747 cases in 1993 to 1,934 cases in 1994 and to 2,147 cases in 1995,
      resulting in an average of 1,891 cases year. The assays used included the
      adenosine triphopsphate inhibition assay,/the collagen droplet embed drug
      response assay, the fluorescent dye assay, the growth chamber assay, the
      histoculture drug response assay, human tumor clonogenic assay, the MTT assay
      (SDI test), the nuclear damage assay, the nude mouse model, the subrenal capsule
      assay and the thymidine incorporation assay (scintillation assay). The
      correlation of in vitro and in vivo results revealed 215 true positive (S/S), 246
      false positive (S/R), 45 false negative (R/S) and 595 true negative (R/R) cases,
      resulting in rates of 47% for true positives and 93% for true negatives, with a
      74% accuracy. We concluded that chemosensitivity testing is widely applied in
      this country and has a high accurate predictive value for advanced carcinomas.

PMID- 10953300
TI  - Vinca alkaloids induce granulocyte-macrophage colony stimulating factor in human
      peripheral blood mononuclear cells.
AB  - Several anti-cancer drugs are known to have proliferation-related effects on
      various cells, such as an activation of some transcription factors and an
      induction of some cytokines. We examined the effect of anti-cancer drugs on
      granulocyte-macrophage colony stimulating factor (GM-CSF) induction in human
      peripheral blood mononuclear cells (PBMC). Increase of GM-CSF protein and mRNA
      were observed in PBMC after exposure to vindesine sulfate (VDS). Induction of GM
      CSF protein was dose-dependent and detectable at VDS concentrations of 0.1
      microgram/ml. This effect was also observed in response to treatment with other
      microtuble-depolymerizing agents, vincristine sulfate and vinorelbine ditartrate,
      but not with cisplatin, etoposide, or paclitaxel. In order to elucidate the
      mechanism of this phenomenon, we examined the effects of cyclohexamide and
      actinomycin D on the expression of GM-CSF mRNA. Both of these drugs completely
      inhibited GM-CSF mRNA expression after VDS exposure, implying that VDS induces de
      novo GM-CSF synthesis in an indirect manner. As a candidate for the initial
      signaling, we next examined the role of the IL-1 beta autocrine or paracrine
      pathways in GM-CSF induction by VDS. IL-1 beta protein and mRNA expression were
      induced after VDS exposure more rapidly (from 4 hours) than expression of GM-CSF
      (protein from 12 hours and mRNA from 8 hours). Addition of anti-IL-1 beta
      antibody partially inhibited induction of GM-CSF by VDS. These results suggest
      that GM-CSF induction by VDS is partially mediated through the initial generation
      of IL-1 beta in PBMC.

PMID- 10953302
TI  - Analysis and classification of proton NMR spectra of lipoprotein fractions from
      healthy volunteers and patients with cancer or CHD.
AB  - Human blood plasma samples from 52 subjects were collected and the very low
      density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density
      lipoprotein (LDL) and high density lipoprotein were isolated by serial ultra
      centrifugation. 600 MHz 1H NMR spectra of the lipoprotein fractions were
      acquired. The methyl and methylene regions in the spectra of VLDL, LDL and HDL
      were utilised in further analyses via Kohonen neural networks (KNN) and
      generative topographic mapping (GTM), two related examples of (unsupervised
      learning) self-organising feature mapping techniques. Systematic variations in
      lipoprotein profiles can be substantially visualised through the use of KNN and
      GTM. The relationship between the sample positions in the Kohonen plot was
      visualised by surface plots of the corresponding VLDL and HDL cholesterol and
      VLDL triglyceride contents. The GTM maps of the VLDL and HDL fractions were used
      to investigate the individual properties of selected samples. A large number of
      the cancer patients were found clustered in the VLDL GTM map, and GTM map
      positions of samples in relation to CHD, diabetes and renal failure could be
      found. Although the study group here considered is heterogeneous in respect to
      age, sex, type of disease and medications within each defined class,
      classification of VLDL and HDL data with probabilistic neural network (PNN) was
      quite successful with respect to the groupings: cancer, CHD, volunteers and other
      (comprising patients with other diseases). Statistics based on 15 independent
      sets of PNN calculations gave true positive fractions usually higher than 0.83
      and false positive fractions lower than 0.088. Attempts to use the corresponding
      LDL data and four classes were uniformly poor although some classifications
      (e.g., volunteer versus CHD) were easily performed.

PMID- 10953304
TI  - Selective induction of apoptosis in human mammary cancer cells (MCF-7) by
      pycnogenol.
AB  - Breast cancer is the second leading cause of cancer death in women in the United
      States. The 1999 Cancer Facts and Figures, published by the American Cancer
      Society, estimates that almost 43,700 women and men will die of breast cancer in
      the United States. In this study, we compared the response of human breast cancer
      cells (MCF-7) and normal human mammary cells (MCF-10) to apoptosis in the
      presence of pycnogenol. Pycnogenol is a mixture of flavonoid compounds extracted
      from the bark of pine trees. MCF-7 and MCF-10 cells were plated out in culture
      dishes and grown in medium containing 0, 40, or 80 micrograms pycnogenol/ml
      culture medium. Cells were harvested at confluency, incubated with DAPI for 15
      min and viewed microscopically for evidence of apoptosis. Apoptosis is detectable
      by morphology, chromatin condensation, nuclear DNA fragmentation, DNA strand
      breakage or apoptotic bodies. DAPI is a DNA-binding fluorescent dye used to
      visualize DNA fragmentation. Apoptosis, as detected by DAPI staining, was
      significantly higher in MCF-7 cells treated with pycnogenol than the untreated
      cells. The presence of pycnogenol did not significantly alter the number of
      apoptotic cells in MCF-10 samples. These results suggest that pycnogenol
      selectively induced death in human mammary cancer cells (MCF-7) and not in normal
      human mammary MCF-10 cells.

PMID- 10953303
TI  - Genistein's "ER-dependent and independent" actions are mediated through ER
      pathways in ER-positive breast carcinoma cell lines.
AB  - Genistein, a natural flavone found in soy has been postulated to be responsible
      for lowering the rate of breast cancer in Asian women. Our previous studies have
      shown that genistein exerts multiple suppressive effects on both estrogen
      receptor positive (ER+) as well as estrogen receptor negative (ER-) human breast
      carcinoma lines suggesting that the mechanisms of these effects may be
      independent of ER pathways. In the present study however we provide evidence that
      in the ER+ MCF-7, T47D and 549 lines but not in the ER-MDA-MB-231 and MDA-MB-468
      lines both presumed "ER-dependent" and "ER-independent" actions of genistein are
      mediated through ER pathways. Genistein's antiproliferative effects are estrogen
      dependent in these ER+ lines, being more pronounced in estrogen-containing media
      and in the presence of exogenous 17-beta estradiol. Genistein also inhibits the
      expression of ER-downstream genes including pS2 and TGF-beta in these ER+ lines
      and this inhibition is also dependent on the presence of estrogen. Genistein
      inhibits estrogen-induced protein tyrosine kinase (PTK) activity. Genistein is
      only a weak transcriptional activator and actually decreases ERE-CAT levels
      induced by 17-beta estradiol in the ER+ lines. Genistein also decreases steady
      state ER mRNA only in the presence of estrogen in the ER+ lines thereby
      manifesting another suppression of and through the ER pathway. Our observations
      resurrect the hypothesis that genistein functions as a "good estrogen" in ER+
      breast carcinomas. Since chemopreventive effects of genistein would be targeted
      to normal ER-positive ductal-lobular cells of the breast, this "good estrogen"
      action of genistein is most relevant to our understanding of chemoprevention.

PMID- 10953305
TI  - Evidence for peroxidative oxidation of substituted piperidine nitroxides, acting
      as apoptosis inducers in Yoshida Sarcoma cells in vivo.
AB  - The results presented herein clearly indicate that nitroxide derivatives--free
      radicals are effective as substrates for one-electron oxidation in the peroxidase
      cycle involving hydrogen peroxide, which have been the subject of considerable
      controversy. This oxidation is catalyzed enzymatically and it might occur in
      tumor cells (in vivo) where the level of ROS (H2O2 and O2.-) is increased. The
      result of this reaction involving hydrogen peroxide is the obligative formation
      of the oxo-ammonium cation involved in the superoxide dismutase-mimic reaction of
      nitroxides with superoxide and/or in reaction with H2O2 leading to superoxide
      formation and regeneration of the parent nitroxide molecule. The efficiency of
      this enzymatically catalyzed oxidation of nitroxide(s) depends on the structure
      of the substituent in position 4 of nitroxide ring as follows: -OCH3 > -NHCOCH3 >
      -NHCOCH2CH3. Notably, the reduced nitroxide salt was not substrate for
      peroxidatic oxidation clearly indicating the importance of the free radical
      moiety of the nitroxide molecule. These findings may have some relevance in the
      recent investigations of antioxidant properties/mechanisms of nitroxides. Based
      on these considerations we hypothesize that the administration of oxidizable free
      radical nitroxide compounds--antioxidants may be a useful strategy in the
      treatment and investigations of cancer diseases. An in vivo study ("Screening
      test of chemicals employing Yoshida Sarcoma animals") was carried out to verify
      whether the structure and/or the chain length of substituent of oxidizable
      nitroxide derivatives--antioxidants could influence their apoptotic activity. The
      results reported in this study are encouraging as we found a limited correlation
      between the molecular oxidative properties of nitroxides under study, their
      structure and antitumor (apoptotic) action. In conclusion, this work demonstrates
      that investigation of the structure-dependent oxidation of antioxidatively acting
      nitroxides can become a very important step in their future screening and
      selection for applications in vivo and in vitro.

PMID- 10953306
TI  - Barrett's esophagus, apoptosis and cell cycle regulation: correlation of p53 with
      Bax, Bcl-2 and p21 protein expression.
AB  - Dysregulation of apoptosis plays an important role in tumor development.
      Mutations of the p53 gene have been reported in adenocarcinomas arising from
      Barrett's metaplasia. The p53 gene is important in the regulation of cell growth
      and apoptosis, with the loss of wild-type activity associated with uncontrolled
      cell-cycle progression and tumor formation. P21 is a cyclin-dependent kinase
      inhibitor that is activated by p53. Bax is a member of the bcl-2 family whose
      function is that of cell-death promoter. We investigated the hypothesis that
      there are significant alterations in the levels of apoptotic protein as well as
      p21 protein expression in the neoplastic progression associated with Barrett's
      metaplasia.

PMID- 10953308
TI  - Apoptosis induced by the sodium butyrate in human gastric cancer TMK-1 cells.
AB  - The effects of sodium butyrate on cell proliferation, gene expression, and
      apoptosis were investigated. Upon exposure to sodium butyrate the cells exhibited
      marked morphological changes, reduced cell proliferation and most cells died
      through apoptosis within 48 hours. In the presence of dexamethasone, however, the
      sodium butyrate-triggered apoptosis was markedly reduced. Studies using the
      glucocorticoid receptor antagonist RU486 indicated that the protective effect of
      dexamethasone was mediated through glucocorticoid receptor. Sodium butyrate
      markedly induced the c-jun proteins level, whereas the c-Myc protein was down
      regulated rapidly. c-Jun protein may play an important role in the action of
      sodium butyrate since its induction preceded the onset of DNA fragmentation. In
      addition, preincubation of the cells with dexamethasone markedly delayed the
      induction of c-jun levels by sodium butyrate. Analysis of the expression of bel-2
      related genes indicated that the Bcl-xS protein level was increased in the
      presence of sodium butyrate and the up-regulation of Bcl-xS by sodium butyrate
      was also blocked by dexamethasone. Taken together, these results indicate that c
      myc, c-jun and Bcl-xS proteins may be involved in the mechanism of sodium
      butyrate-triggered apoptosis in these cells.

PMID- 10953307
TI  - A genomic response of H-358 bronchiolar carcinoma cells to MK 886, an inhibitor
      of 5-lipoxygenase, assessed with a cDNA array.
AB  - Incomplete programmed cell death is one explanation for the escape of cancer
      cells from therapy. Inhibitors of the enzyme 5-lipoxygenase reduce proliferation
      and initiate programmed cell death in many different types of malignantly
      transformed cells. The 5-lipoxygenase inhibitor, MK 886. induces an atypical form
      of programmed cell death in H-358 bronchiolar lung cancer cells. A genomic
      response of H-358 cells after 24 hr of culture at a 40 uM concentration that
      inhibited proliferation was analyzed with a Clontech human cDNA array containing
      588 cDNAs corresponding to identified genes. The data grouped into 3 major
      categories and initial conclusions regarding countervailing, cellular stress,
      programmed cell death, DNA damage and repair mRNA-responses as possible reasons
      for escape from the antiproliferative response are discussed. The use of cDNA
      arrays to estimate the extent to which malignantly transformed cells respond to
      therapy or why they do not and so infer prognosis and identify possible
      therapeutic modifications is indicated.

PMID- 10953309
TI  - Establishment and characterization of a paclitaxel-resistant human non-small cell
      lung cancer cell line.
AB  - We have established a paclitaxel-resistant mutant cell line called H460/TAX which
      was derived from human non-small cell lung cancer (NSCLC) H460. A 64-fold greater
      resistant was shown in our assay as compared with the parental cells. High
      specificity of drug resistance was also observed since this mutant was not cross
      resistant to several other anticancer drugs. Drug accumulation in H460/TAX was
      significantly less than that in H460. Many endogenous protein profiles were
      intact, including the expression level of P-glycoprotein, multidrug resistance
      associated protein, the 70 kDa heat shock proteins as well as the phosphorylation
      of Bcl-2 in H460/TAX cells, except that the total amount of alpha- and beta-
      tubulins was higher in H460/TAX than in H460 cells. Higher drug concentration and
      longer treatment for paclitaxel were required in H460/TAX to exert the
      phosphorylation of keratin 19 which was then accompanied by reorganization of the
      intermediate filament and the microtubule networks. Since all of the
      aforementioned factors involved in paclitaxel-resistance in other systems were
      not found to be significantly altered in H460/TAX, there must be other paclitaxel
      resistance mechanisms(s) which remains to be identified in human lung cancers.

PMID- 10953310
TI  - 5-fluorouracil sensitivity and dihydropyrimidine dehydrogenase activity in
      advanced gastric cancer.
AB  - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of
      5-fluorouracil (5-FU) catabolism. Several studies have demonstrated the clinical
      importance of DPD in cancer patients, suggesting that the efficacy of 5-FU may be
      related to DPD activity in tumor tissue. In the present study, DPD activity and
      chemosensitivity to 5-FU were evaluated in advanced gastric cancer. MATERIALS AND
      METHODS: Thirty-four gastric cancers from 32 patients were studied and
      chemosensitivity to 5-FU was evaluated by histoculture drug response assay.
      RESULTS AND CONCLUSION: DPD activity and tumor inhibition of 5-FU among all cases
      showed no significant correlation, but among 14 histologically differentiated
      cases significant correlation was observed. DPD activity may be useful in
      determining the 5-FU sensitivity of differentiated gastric cancer.

PMID- 10953311
TI  - Relationship between binuclear and multinuclear cells in giant cell tumor of
      bone.
AB  - Giant cell tumor of bone (GCT) consists of stromal and multinuclear type tumor
      cells. Although most people believe that the stromal cells are mononuclear, we
      recently found the existence of many binuclear cells among stromal cells using
      DNA cytofluorometric examination. This study, using 18 tumors of GCT was
      conducted to elucidate the cell biological significance of the binuclear cell,
      especially its relationship to multinuclear cell formation or tumor cell
      proliferation. The investigation was carried out by means of DNA-RNA
      cytofluorometry with acridine orange (AO) and histological method. Using
      fluorescence microscopic observation, we counted the numbers of both mononuclear
      and binuclear cells and calculated the index of % BNC, which expresses the
      frequency (percentage) of binuclear cells in a population of mononuclear and
      binuclear cells. The index of % S-G2 obtained by DNA-RNA cytofluorometry showed
      the frequency (percentage) of mononuclear cells in the S and G2 phases of the
      cell cycle. In the histological study, we counted the numbers of multinuclear
      giant cells with more than 3 nuclei in the cytoplasm and stromal cells including
      mononuclear and binuclear cells and calculated MNS/SC, which showed the
      percentage of multinuclear cells in the stromal cells in the microscopic field.
      Eight tumors showed a value of % BNC greater than 10% and 2 had a value of 40%.
      The index of % BNC significantly correlated with the average value of MNC/SC in
      all tumors. There was no significant correlation between % BNC and the average
      value of % S-G2, in 18 tumors although 4 tumors having a % BNC value greater than
      20% showed a % S-G2 value greater than 12% in 18 tumors. These results revealed
      the presence of many binuclear cells among stromal cells of GCT and suggested
      that these binuclear cells might be formed in association with the active
      proliferation of mononuclear cells and closely relate to the formation of
      multinuclear giant cells.

PMID- 10953312
TI  - Clinical value of bile for the detection of mutant K-ras from colorectal liver
      metastases.
AB  - In 25% of patients diagnosed with colorectal cancer, hepatic metastases are not
      detected at presentation of the colorectal primary but develop during follow-up.
      Early detection of these metastases may improve the chance of cure by surgical
      resection. We hypothesised that in patients with occult hepatic metastases,
      tumour DNA might be detected in bile which could be collected during resection of
      the colorectal primary. To test this hypothesis, bile from the gall bladder was
      collected from 17 patients scheduled for resection of evident hepatic metastases
      (> 2 cm3) from a previously resected colorectal primary. Mutation analysis of the
      metastases identified five patients (34%) with a K-ras gene mutation in the
      tumour tissue. These cases were selected for bile analysis for mutant K-ras. Non
      mutated DNA could be amplified from all the bile samples, but mutant K-ras could
      only be detected in bile from one patient. False negative results due to
      technical deficits could be ruled out by control experiments showing a high DNA
      isolation efficiency and high sensitivity of the mutation detection method. It is
      concluded that hepatic metastases, in contrast to pancreatic cancers, do not
      (regularly) shed mutated DNA into the bile. Hence, molecular screening of bile
      seems of only limited clinical value for the detection of occult liver
      metastases.

PMID- 10953313
TI  - Interaction between chlorogenic acid and antioxidants.
AB  - The interaction between chlorogenic acid (CGA) and antioxidants was investigated
      by two different parameters: radical intensity and cytotoxicity induction. ESR
      spectroscopy shows that CGA produced radicals under alkaline condition. The CGA
      radical was scavenged by 100-300-fold lower concentrations of sodium ascorbate or
      N-acetyl-l-cysteine (NAC), whereas the ascorbate radical was not completely
      scavenged by CGA. The cytotoxic activity of CGA against human oral tumor cells
      (HSC-2, HSG) was completely eliminated by lower concentrations of sodium
      ascorbate or NAC, whereas that of sodium ascorbate or NAC was only slightly
      reduced by CGA. The present study demonstrated that CGA induces cytotoxicity by
      its radical-mediated oxidation mechanism and suggests the applicability of ESR
      spectroscopy for the screening of drug to drug interaction.

PMID- 10953314
TI  - Effects of quercetin on the cell growth and the intracellular accumulation and
      retention of adriamycin.
AB  - In this study, we examined the inhibitory effects on cell growth and the effects
      of quercetin on intracellular accumulation of adriamycin (ADR) in wild type
      Ehrlich ascites tumor cells (wild EAT cells) and their ADR-resistant strain.
      Quercetin strongly inhibited growth in both strains. Cell growth reached a
      plateau at 3.5 days in the wild type EAT cells and at 7 days in the ADR-resistant
      strain. The inhibitory concentration in 50% of the ADR-resistant cells on day 7
      (24 microM) was twice that of the wild type EAT cells on day 4 (12 microM) after
      continuous treatment with quercetin. Quercetin decreased the ADR accumulation in
      the wild type cells but did not affect it in the ADR-resistant cells. Further,
      quercetin did not affect the retention of ADR in either strain. These results
      indicated that quercetin decreased ADR accumulation without extruding ADR in the
      wild type EAT cells. ADR accumulation in the ADR-resistant cells treated with
      quercetin for 7 days was increased with increasing concentrations of quercetin.
      Moreover, ADR accumulation in the ADR-resistant cells treated with 50 microM
      quercetin for 7 days, increased to 186.6% and to 181.9% of that in untreated
      cells after 60 minutes and 120 minutes incubation, respectively, whilst it
      increased to 70% from 37.5% of that in the wild type EAT cells after 60 minutes
      incubation. These findings indicated that quercetin might reverse ADR-resistance.

PMID- 10953315
TI  - Immunohistochemical detection of cytokeratin 18 and its neo-epitope in human
      salivary glands and pleomorphic adenomas.
AB  - An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which
      reacts with the product released by the cleavage of cytokeratin 18 (CK18) by
      activated caspase, was used to investigate the extent of apoptosis in human
      salivary glands and pleomorphic adenomas. The distribution of CK18 in the
      salivary glands and adenomas was also determined and compared with that of the
      product detected by MAb M30. CK18 was detected in the cytoplasm of serous acinar
      and ductal cells in normal human salivary glands. In pleomorphic adenomas, CK18
      was observed mainly in the tumor cells of duct-like structures, but not in those
      of myxomatous or chondroid tissues. Positive MAb M30 reaction products were found
      in the cytoplasm of acinar cells in the restricted lobules of normal salivary
      glands and in the luminal contents of duct-like structures in pleomorphic
      adenomas. These results suggest that a mechanism which suppresses apoptosis may
      be linked to the growth of human pleomorphic adenomas.

PMID- 10953316
TI  - Enhanced expression of translation factor mRNAs in hepatocellular carcinoma.
AB  - Several studies have demonstrated elevated expression of translation factor mRNAs
      in malignant tissues. In this study, using primary human hepatocellular carcinoma
      (HCC) tissues, we examined gene expression of translation factors, including 2
      eukaryotic initiation factors (eIFs-4A1, -4E), 4 elongation factors (eEFs-1
      alpha, -1 gamma, -1 delta, and -2) and 10 ribosomal proteins (Rps P1, P2, S10,
      L35, L5, L39, L9, L6, S3a and S17), whose mRNA expression has never been examined
      in HCC. Our results demonstrated that all the mRNAs examined were up-regulated in
      HCC tissues. Among 7 HCC tissues of different histological grades, the expression
      of these mRNAs remained at basal levels in a well to moderately differentiated
      (W/M-) HCC, was coordinately up-regulated in moderately differentiated (M-) HCCs.
      In moderately to poorly differentiated (M/P-) HCCs, the expression of eEFs-1
      gamma, -1 delta, -2, Rps P0 and L9 mRNAs was further up-regulated along with the
      histological grading. These results therefore suggest that coordination and
      specific activation of translation factor genes might be involved in the process
      of liver carcinogenesis.

PMID- 10953317
TI  - The p73 gene is not mutated in oligodendrogliomas which frequently have a deleted
      region at chromosome 1p36.3.
AB  - An allelic loss of the chromosome 1p36 region is frequently found in
      oligodendrogliomas, which suggests the presence of putative tumor suppressor
      gene(s) in the region. Since the p73 gene, which encodes a protein with
      significant homology with p53, is mapped to the 1p36.33 region, we examined
      genetic alterations of the p73 gene in oligodendrogliomas. We screened 10
      specimens for mutation throughout the p73 coding regions by polymerase chain
      reaction (PCR)-single strand conformation polymorphism analysis and by sequencing
      aberrantly migrated PCR products. We found several polymorphic nucleotide
      changes, but no somatic mutations that caused an amino acid change. The p73 gene
      is thus unlikely to be a tumor suppressor gene for oligodendrogliomas.

PMID- 10953318
TI  - The recombinant human histones H1 zero and H1.2 cause different toxicity profiles
      on the human leukemia cell line K562.
AB  - The human histones H1 zero and H1.2 were expressed in E. coli and purified to
      homogenity. Their cytotoxicity on the human leukemia cell line K562 and on PBMC
      from healthy volunteers was compared with the cytotoxic effect of a bovine
      histone H1 preparation. In this preparation, histone H1.2 was identified as the
      main compound. All three histone preparations induced a significant dose
      dependent toxicity on the leukemia cell line. Compared with the recombinant
      histone H1 zero, the bovine preparation and recombinant H1.2 showed stronger
      cytotoxicities. Cytotoxic effects on K562 cells were observed immediately after
      addition of the histones, whereas the histone preparations failed to induce
      significant cytotoxicity on PBMC during the first hour of incubation. However,
      after 24 hours all three histone preparations induced toxic effects on PBMC which
      were comparable to those observed on the leukemia cell line.

PMID- 10953319
TI  - Effect of coumarins on HL-60 cell differentiation.
AB  - Twenty-eight coumarins, including 7 furocoumarins, were examined for their
      activity of induction of terminal differentiation of human promyelocytic leukemia
      cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase,
      specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7
      dihydroxy-4-methylcoumarin and imperatorin had strong activity among the
      coumarins examined. HL-60 cells treated with these coumarins differentiated into
      mature monocyte/macrophage. The structure-activity relationship established from
      the results revealed that 6,7-dihydroxy moiety had an important role in the
      induction of differentiation of HL-60.

PMID- 10953320
TI  - Inhibition of tat-mediated HIV-1-LTR transactivation and virus replication by
      sulfhydryl compounds with chelating properties.
AB  - D-Penicillamine, a structural analog of cysteine, has the ability to chelate
      metal ions and reacts with cysteine. We have shown earlier that D-Penicillamin is
      a potential inhibitor of tat-mediated transactivation of HIV-1-LTR (14) and
      possesses anti-HIV-1 activity (23). Following this approach, we evaluated the
      anti-tat and anti-HIV-1 activity of several sulfhydryl compounds with chelating
      properties. The tested compounds: N-(2-Mercapto-propionyl)-glycin (MPG), 2,3
      Dimercapto-propanol (DMP) and 2,3-Dimercapto-propane-sulfonic acid (DMPS)
      exhibited an inhibitory effect on the tat-mediated transactivation in Jurkat
      cells, as well as in U937 cells. The highest inhibitory response was shown by DMP
      leading to about 50% inhibition of transactivation in Jurkat cels and an 80%
      inhibition in U937 cells. On the contrary, DMPS (30 micrograms/ml) had no
      inhibitory effect in U937 cells, but did exhibit a 50% inhibition of
      transactivation in Jurkat cells at 30 micrograms/ml. The antiviral activity of
      DMP and DMPS was evaluated in H9 cells. In the concentration range which is
      effective for antiviral effect, both the compounds were highly cytotoxic.
      Mercapto-propionyl-glycin, although a weak inhibitor of transactivation, was able
      to inhibit synctia formation to more than 90% and inhibit the viral antigene
      expression to about 70%. The concentration of MPG needed to achieve this
      antiviral effect was very high, but it had no cytotoxicity at this concentration.
      We suggest that a search for compounds using this approach may be useful in
      developing potential inhibitors of tat-mediated transactivation.

PMID- 10953321
TI  - Cytotoxicity and radical intensity of eugenol, isoeugenol or related dimers.
AB  - To investigate the possible link between radicals and cytotoxicity of eugenol
      related compounds, dimer compounds were synthesized from eugenol (4-allyl-2
      methoxyphenol) or isoeugenol (4-propenyl-2-methoxyphenol): bis-eugenol (3,3'
      dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol); dehydrodiisoeugenol (2-(3
      methoxy-4-hydroxyphenyl)-3-methyl-5-(1-propenyl)-7-methoxy-2,3-
      dihydrobenzofuran) and alpha-di-isoeugenol (r-l-ethyl-5-hydroxy-t-3-(4-hydroxy-3
      methoxyphenyl)-6-methoxy-c-2- methylindane). Both the cytotoxic activity and the
      DNA synthesis inhibitory activity of these compounds against a salivary gland
      tumor cell line (HSG) and normal human gingival fibroblast (HGF) were decreased
      in the order of: dehydrodiisoeugenol, alpha-di-isoeugenol > isoeugenol > eugenol
      > bis-eugenol. Electron spin resonance (ESR) spectroscopy showed that
      dehydrodiisoeugenol, alpha-di-isoeugenol and eugenol, but not isoeugenol and bis
      eugenol, produced phenoxyl radicals under alkaline condition (pH > 9.5). However,
      benzyl radicals were produced during the dimerization of isoeugenol to
      dehydrodiisoeugenol. The radical intensity of alpha-di- and dehydrodiisoeugenol
      appeared at relatively later incubation time than eugenol, suggesting that their
      phenoxyl radical was more stable than that of eugenol. Such a phenoxyl radical is
      produced by scavenging free radicals, during the inhibition of lipid
      peroxidation. Higher cytotoxic activity of isoeugenol dimers was thought to be
      induced by interaction with cell membranes via the lipophilic radical. The
      present study supports the notion that relative cytotoxicity of chemicals can be
      evaluated by measuring the radical intensity using ESR.

PMID- 10953322
TI  - Cytotoxic activity of low molecular weight polyphenols against human oral tumor
      cell lines.
AB  - A total of 150 chemically-defined natural and synthetic polyphenols (flavonoids,
      dibenzoylmethanes, dihydrostilbenes, dihydrophenanthrenes and 3-phenylchromen-4
      ones), with molecular weights ranging from 224 to 824, were investigated for
      cytotoxic activity against normal, tumor and human immunodeficiency virus (HIV)
      infected cells. They showed higher cytotoxic activity against human oral squamous
      cell carcinoma HSC-2 and salivary gland tumor HSG cell lines than against normal
      human gingival fibroblasts HGF. Many of the active compounds had a hydrophilic
      group (hydroxyl group) in the vicinity of a hydrophobic group (prenyl, phenyl,
      methylcyclohexene or methylbenzene moiety), similar to isoprenoid-substituted
      flavones. Substitution of hydrophobic group (prenyl or geranyl group) did not
      significantly change the cytotoxic activity of flavanones, isoflavans, chalcones
      or 5-hydroxy-3-phenoxychromen-4-ones. However, the prenylation(s) of an
      isoflavone and a 2-arylbenzofuran significantly enhanced the cytotoxic activity.
      Agarose gel electrophoresis showed that active components induced
      internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells,
      but not in HSC-2 cells. Most of the polyphenols failed to reduce the cytophathic
      effect of HIV infection in MT-4 cells.

PMID- 10953323
TI  - Sensitivity of cyclin E-overexpressing cells to cisplatin/taxol combinations.
AB  - Combinations of anticancer drugs, referred to as "combinatorial" chemotherapy, is
      often used in the treatment of cancer patients. Recent advances in our
      understanding of cell cycle and cellular stress responses may be viewed in the
      context of responses to anticancer drugs. A desired outcome is cell death
      preferentially occurring in cancer cells. We report that cyclin E, an oncogene
      that is deregulated in breast and other human cancers, can sensitize cancer cells
      to cisplatin/taxol combinations. The drug combination may selectively induce
      apoptosis in cyclin E-overexpressing cells.

PMID- 10953324
TI  - Leptin contributes to the protection of human leukemic cells from cisplatinum
      cytoxicity.
AB  - Leptin (ob gene) and its cognate receptor (obr) are relevant for fat metabolism.
      Obr shares homology with the IL-6 signal transducer gp130 and is expressed in
      hematopoietic cells. Since cytokines and growth factors regulate both
      hematopoiesis and response to chemotherapy, we tested the hypothesis of whether
      leptin protects leukemic cells from cytotoxicity of cisplatinum. Antisense
      phosphorothioate oligodeoxynucleotides (ODNs) and antisense peptide nucleic acids
      (PNAs) complementary to the obr gene were first tested for their growth
      inhibitory activity in obr expressing leukemic cells. Liposome-mediated
      transfection of ODNs (1-2 microM) or PNAs (0.01-1 microM) inhibited growth up to
      50%. Combination treatments of cisplatinum and 0.01 microM PNA reduced growth
      more than cisplatinum alone. Vice versa, recombinant human leptin (rhL)
      diminished cisplatinum-induced growth inhibition. Finally, we investigated
      whether rhL affects cisplatinum-induced DNA damage and repair in the housekeeping
      gene beta-actin by means of real time TaqMan polymerase chain reaction. RhL
      reduced DNA damage and increased DNA repair. The effects are, however, modest and
      leptin is probably not the only player in the armory of growth factors which
      affect drug resistance.

PMID- 10953325
TI  - Inhibition of growth and regulation of IGFs and VEGF in human prostate cancer
      cell lines by shikonin analogue 93/637 (SA).
AB  - BACKGROUND: Insulin-like growth factors (IGFs) are important mitogens and are
      involved in normal and malignant cellular proliferation. IGFs and IGF binding
      proteins (IGFBPs) regulate the prostatic cell growth and reduction/blocking of
      IGFs has been suggested to be of therapeutic value in prostate cancer. beta,beta
      dimethyl acryl shikonin, an extract from the roots of plant Arnebia nobilis has
      been shown to have anticancer properties but was found to be toxic. Subsequently,
      several analogoues of beta,beta-dimethyl acryloyl shikonin were synthesized and
      one of them shikonin analogue 93/637 (SA) was significantly less toxic compared
      to beta,beta-dimethyl acryloyl shikonin. MATERIALS AND METHODS: We have
      investigated the effect of SA on prostate cancer cell (DU 145, LNCaP and PC-3)
      growth and expression of IGFs (IGF-I, IGF-II and IGF-I receptor (IGF-IR)), IGFBP
      3 and vascular endothelial growth factor (VEGF). RESULTS: SA had growth
      inhibitory effect on PC-3 cells in a dose dependent manner. It also showed slight
      inhibitory effect on the growth of DU 145 and LNCaP cells at low doses ranging
      from 250 nM to 1 microM and has moderate inhibitory effect at concentrations 2.5
      microM and above. Lactate dehydrogenase (LDH) activity assays indicated cellular
      damage, only at higher concentrations of SA that are greater than 1 microM. Gene
      expression studies by RT-PCR have demonstrated a decrease in mRNAs of IGF-II in
      DU 145, IGF-I, and IGF-IR in LNCaP, and IGF-II and VEGF in PC-3 cells and an
      increase in IGFBP-3 in both DU 145 and PC-3 cells by treatment with SA.
      CONCLUSIONS: The results demonstrate the inhibitory effect of SA on cellular
      growth and IGFs specifically in PC-3 cells and suggest a potential therapeutic
      use in treatment of prostate cancer.

PMID- 10953326
TI  - Reduction in p53 gene dosage diminishes differentiation capacity of osteoblasts.
AB  - BACKGROUND: Loss of p53 function is seen in a large number of human tumors
      including osteosarcoma, and in previous studies we have demonstrated a close
      relationship between wild type p53 and osteoblasts differentiation. In the
      present study we attempted to understand the relationship of bone growth and
      differentiation to p53 gene dosage by studying calvarial osteoblasts obtained
      from p53 deficient mice. RESULTS: Growth rules were higher in p53 -/- than p53 +/
      osteoblasts when passaged for different lenght of time. However, loss of the
      remaining wt allele occurred early during culturing of the p53 +/- cells, and
      these cells became immortalized with growth rates and doubling times reaching
      values higher than the p53 -/- homozygotes. Early passage osteoblasts were used
      to study differentiation properties of these osteoblasts in vitro by exposing
      them to differentiation promoting media. While osteocalcin, a marker protein of
      differentiated osteoblasts, was synthesized in both cell types, p53 -/- cells
      consistently showed higher levels of osteocalcin activity, and in long term
      cultures formed more bone spicules that p53 +/- cells. Basal osteocalcin promoter
      activity was similar in both cell types, but transient transfection of wt p53
      into the cells produced a larger activation of the promoter in p53 +/- cells,
      than in p53 -/- cells. Sections of long bones from neonatal p53 +/- and -/- were
      examined histologically, and no gross abnormalities were detected. TUNEL staining
      of the bones showed apoptotic cells in the growth plate and lining cells of both
      p53 genotypes, but apoptosis in hypertrophic chondrocytes was seen only in p53 +/
      bones. CONCLUSION: Overall our studies show that osteoblastic differentiation
      becomes a p53 dependent process only when at least one functional copy of the p53
      gene is present during development.

PMID- 10953327
TI  - Alkylator resistance in human B lymphoid cell lines: (1). Melphalan accumulation,
      cytotoxicity, interstrand-DNA-crosslinks, cell cycle analysis, and glutathione
      content in the melphalan-sensitive B-lymphocytic cell line (WIL2) and in the
      melphalan-resistant B-CLL cell line (WSU-CLL).
AB  - Two human B lymphoid cell lines WIL2 (melphalan sensitive. ***IC50:8.57 +/- 1.08
      mM) and WSU-CLL (melphalan resistant, ***IC50:223.18 +/- 6.45 mM) were used as
      models to study alkylator resistance in human lymphoid cells. Melphalan transport
      studies demonstrated decreased initial melphalan accumulation in WSU-CLL cells as
      compared to WIL2 cells. Lineweaver-Burk plots of the rate of initial melphalan
      uptake showed an approximately 3.5-fold decrease of Vmax in WSU-CLL cells as
      compared to WIL2 cells. Melphalan transport was inhibited by 2-amino
      bicyclo[2,2,1] heptane-2-carboxylic acid(BCH) in both cell lines, indicating that
      the amino acid transport (System L, which is sodium independent and inhibited by
      BCH) is functional in these two cell lines. Only a minor degree of inhibition of
      melphalan transport was noted after sodium depletion (System ASC, which is sodium
      dependent and unaffected by BCH). Interstrand-DNA-cross-link formation showed a
      highly significant correlation with in-vitro cytotoxicity in both two cell lines.
      However, the melphalan concentration at which such interstrand DNA cross-linking
      occurred differed significantly when WIL2 cells and WSU-CLL cells were compared.
      The kinetics of interstrand-DNA-cross-link formation and removal following
      treatment with melphalan also differed significantly, with WSU-CLL cells, showing
      a much more rapid rate of removal of interstand DNA cross-links as compared to
      WIL2 cells. Cell cycle analysis showed that melphalan treatment resulted in the
      progressive arrest of the WSU cells in G1 and G2 phases. But WIL2 cells failed to
      enter G1 or G2 arrest after melphalan treatment, suggesting an increased rate of
      DNA repair occurring in melphalan-resistant WSU-CLL cells. There was no
      significant difference between the two cell lines in regard to either glutathione
      content or glutathione-S transferase activity. These findings indicate that
      multiple factors are associated with alkylator resistance in lymphoid cells
      including alteration of uptake, DNA repair and cell cycle progression. However no
      evidence for alteration in glutathione content and glutathione-S-transferase
      activity was found.

PMID- 10953328
TI  - Alkylator resistance in human B lymphoid cell lines: (2). Increased levels of
      topoisomerase II expression and function in a melphalan-resistant B-CLL cell
      line.
AB  - Previous studies have demonstrated alkylating (melphalan) resistance in the B-CLL
      derived WSU-CLL cell line as compared to WIL2 B lymphocytic cells. Nuclear
      extracts from WSU-CLL cells demonstrate a highly significant increase in DNA
      topoisomerase II activity as compared to WIL2 cells. Western blot analysis showed
      the level of topoisomerase II proteins expressed in WSU-CLL cells to be increased
      as compared to WIL2 cells. WSU-CLL cells were 5.24-fold more sensitive than WIL2
      cells to the cytotoxic effect of the topoisomerase II inhibitor doxorubicin. No
      difference in topoisomerase I activity or of the level of topoisomerase I protein
      expression was observed comparing the two cell lines. The sensitivity to the
      cytotoxic effects of topoisomerase I inhibitor, camptothecin, did not differ in
      WSU-CLL and WIL2 cell lines. Pre-incubation with doxorubicin significantly
      increased melphalan induced interstrand-DNA-crosslink formation and cytotoxicity
      in WSU-CLL cells as compared to WIL2 cells. The affinity of topoisomerase II for
      WSU-CLL UV-irradiated-crosslinked DNA was increased 2.84-fold as compared to that
      of WSU-CLL native DNA. The affinity of topoisomerase II for both UV-irradiated
      (crosslinked) and for native DNA was significantly decreased after doxorubicin
      pretreatment. Measurement of DNA polymerase beta and DNA polymerase beta revealed
      significant elevations in DNA polymerase beta (58.82 +/- 3.67 units/mg protein in
      WSU-CLL cells, as compared to 27.82 +/- 4.39 units/mg protein in WIL 2 cells; p <
      0.01) but not DNA polymerase beta (0.82 +/- 0.11 units/mg protein in WSU-CLL
      cells, compared to 0.74 +/- 0.09 units/mg protein in WIL2, p > 0.05). However,
      exposure to aphidicolin (an inhibitor of DNA polymerase a) failed to increase
      melphalan induced cytotoxicity suggesting that although DNA polymerase a activity
      was increased in WSU-CLL cells the mechanisms of resistance does not involve this
      specific DNA repair pathway. Elevated topoisomerase II activity and the increased
      affinity of topoisomerase II for crosslinked DNA in melphalan resistant cells
      appears to be the major factor responsible for alkylator resistance by changing
      DNA topology and thereby facilitating DNA repair.

PMID- 10953329
TI  - Photodynamic activity of hypericin in human urinary bladder carcinoma cells.
AB  - Recently, we reported the selective accumulation of hypericin in transitional
      cell carcinoma cells following intravesical instillation of hypericin in humans.
      This observation infers that hypericin, a potent photosensitizer, could be used
      as a selective PDT (photodynamic therapy) tool against superficial bladder
      cancer. The aim of the present study was to investigate in vitro whether
      hypericin exhibits specific affinity for TCC transitional cell carcinoma) bladder
      cells and to assess its photocytotoxic effect. Three human TCC cell lines (J-82,
      T-24 and RT-4), a chemically induced rat TCC cell line (NBT-II), but also non
      bladder carcinoma cells (HeLa, A431, MCF-7 and MCF-***ADR) and normal cells
      (HEL229, RPE and PHK), were used in this comparative study. Flow cytometric
      analysis of cells treated with different hypericin-containing vehicles for
      various incubation times (2 hours or 24 hours) indicated that short exposure of
      the cells (2 hours) to hypericin in the absence of serum results in the highest
      intracellular accumulation of the compound. As expected, prolonging the
      incubation time increased both the cellular accumulation and photocytoxicity of
      hypericia. With the exception of the RT-4 and MCF-7 cells (which were less
      sensitive to hypericin), all the other carcinoma cell lines examined showed equal
      sensitivity to the photoactivated hypericia, independently of their histological
      origin (bladder or non-bladder). Moreover, normal cells exhibited the same
      pattern of hypericin photosensitivity as shown by the cancer cells, indicating
      that, in cultured cells, hypericin cellular uptake and subsequent photokilling is
      not selective. This suggests that in vivo factors other than the cancer cells
      themselves are responsible for the specific accumulation of hypericin in
      urothelial carcinoma lesions.

PMID- 10953330
TI  - Chemo-immunotherapy of ovarian cancer in a murine tumour model.
AB  - BACKGROUND: As a majority of ovarian cancer patients will ultimately develop
      recurrent disease, there is an urgent need for alternative or additional
      approaches in the treatment of this cancer. MATERIALS AND METHODS: The antitumour
      effect of i.p. administered cisplatin, liposomal muramyltripeptide
      phosphatidylethanulamine (L-MTP-PE) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) were investigated using an i.p. growing murine ovarian tumour.
      Tumour growth was followed by measuring weight and survival of the mice. RESULTS:
      An i.p. injection of L-MTP-PE in non-tumour bearing mice resulted in an
      approximately 10-fold increase in the number of peritoneal cells, which were
      highly cytotoxic. Nonetheless, treatment of mice inoculated with MOT cells with
      cisplatin, L-MTP-PE and GM-CSF using different treatment schedules did not result
      in inhibited tumour growth when compared to treatment with cisplatin alone.
      CONCLUSION: Although L-MTP-PE showed an enormous increase in peritoneal cells
      with high tumour cytotoxic capacity, the immunotherapeutic treatment with GM-CSF
      and L-MTP-PE, aimed at the recruitment and activation of the peritoneal cell
      population, failed to result in a significant prolongation of survival.

PMID- 10953331
TI  - The paradoxical apoptotic effects of novel nitroxide antioxidants on Yoshida
      sarcoma cells in vivo: a commentary.
AB  - Here we show for the first time that the model nitroxide derivatives, free
      radical or its reduced piperidinium salt, suppressed cytotoxicity of ROS (O2 and
      H2O2) generated outside the cells (B14 line, model for neoplastic phenotype) in
      ***. The nitroxides prevented the decrease in the number of *** caused by
      exogenous O2- and H2O2 at concentrations which were not themselves cytotoxic. In
      the present study, we have also shown that a very substantial difference in the
      cell response occurred when the model rat tumor cells (Yoshida Sarcoma ascites)
      were treated in vivo with six novel synthesized nitroxide antioxidants. A number
      of tumor cells displayed morphological characteristics of apoptosis. This effect
      was comparable to those observed for other nitroxyls under similar experimental
      conditions. Since the increase in the ROS generation followed by apoptotic
      changes of nuclei is the consistent recent finding in various experimental models
      of apoptosis, one fundamental question was raised: why nitroxide antioxidants
      paradoxically act as apoptosis inducers in vivo? Taking together the results
      presented here and in our previous works, it seems reasonable to suggest that
      nitroxide-antioxidants improve the endogenous "antioxidants reserve" and action
      can induce a reductive stress as opposed to an oxidative stress, triggering a
      cascade of dose-dependent processes involving indirectly an antioxidant
      mechanism(s) and resulting in the apoptotic death of cancer cells in vivo. The
      SAR (structure activity relationship) revealed that either the substituent
      structure at 4-position of the nitroxide ring or its oxidation state are
      determinant for the degree of the observed differences in the apoptotic potency
      of nitroxide derivates in vivo.

PMID- 10953332
TI  - Induction of transendothelial migration in normal and malignant human T
      lymphocytes.
AB  - Activated CD 3+ enriched human peripheral blood T cells exhibited potent capacity
      for transendothelial migration through HUVEC layers in the absence of T cell ***.
      In contrast, malignant human T cell lines *** no or negligible ability of
      transendothelial migration in the absence of chemoattractants. Time lapse studies
      of transendothelial migration of activated CD 3+ enriched peripheral blood T
      cells through a HUVEC layer showed that the first T cells were detected in the
      lower compartment of a tissue culture insert after 1 hour and that migration
      increased to reach a maximum of 25 x 10(4) T cells/hr after 24 hours. Adhesion
      assays of human T cell lines demonstrated that all T cell lines were capable of
      adhesion to HUVEC and that adhesion of T cells to HUVECs was primarily mediated
      by CD11a/CD18 and ICAM-1 interactions. Furthermore, transendothelial migration of
      CD 3+ enriched human peripheral blood T cells was inhibited by pretreating the T
      cells with anti-CD 18 monoclonal antibodies. The inability of malignant T cells
      to migrate through HUVEC layers in the absence of chemoattractants was not due to
      poor motility per se, since both normal and malignant T cells migrated well on
      extracellular matrix components as determined by using Boyden chambers.
      Crosslinking of alpha 1 beta 2 and alpha 4 beta 1 with immobilized monoclonal
      antibodies induced motile behaviour in activated CD 3 enriched human peripheral
      blood T cells but not in malignant T cell lines. In conclusion, the differences
      in the ability of transendothelial migration between normal and malignant human T
      cells in the absence of chemoattractants is primarily due to the differences in
      the capacity of alpha 1 beta 2 and alpha 4 beta 1 to trigger motile behaviour in
      the separate cell types.

PMID- 10953333
TI  - p53 analysis of laryngeal cancer in exon 4 to 9.
AB  - p53 gene mutations are a common genetic alteration in human cancer and codon
      72/exon 4 polymorphism of the p53 gene has been implicated in cancer risk.
      Therefore in this study the p53 gene status of 32 shock-frozen tumor specimens
      from larynx carcinomas was analyzed by PCR and sequencing of exon 4 through 9.
      Four mutations (12.5%) in exon 5, 7, 8 and 9 were detected in the carcinoma
      specimen. Analysis of codon 72 revealed in eight cases a homozygosity for proline
      (CCC) and in 24 cases heterozygosity or homozygosity for arginine (CGC). The
      group with the proline/proline genotype had a median age 10.3 years lower than
      the remaining patients and included the only two non-smokers. Firstly, these
      results confirm the p53 mutational status of laryngeal cancer without any
      clinical correlation and secondly may suggest an oncogenic potential for the
      proline/proline genotype of codon 72 for laryngeal cancer as has already been
      assumed for lung cancer.

PMID- 10953334
TI  - Effects of MDR reversing agent combinations on the 3H-daunomycin accumulation in
      drug-sensitive and drug-resistant human cancer cells.
AB  - BACKGROUND: As multidrug resistant (MDR) tumour cells generally exhibit a drug
      accumulation deficit, the effects of three prototype modulators and their
      combinations were investigated by studying the modulation of 3H-dounomycin
      cellular accumulation. MATERIALS AND METHODS: Two cell lines derived from a rhino
      pharingeal human carcinoma, either sensitive (KB-3-1) or selected as MDR (KB-A1)
      were used. Verapamil (10mumol.L-1), PSC 833 (lmumol.L-1) and S9788 (5mumol.L-1)
      were tested alone or in association two by two. The cells were characterized by
      reverse transcriptase polymerase chain reaction (RT-PCR) in terms of pleiotropic
      resistance gene expression. RESULTS: A strong mdr1 and a light LRP gene
      expression were found in KB-A1 resistant cells compared to KB-3-1, whereas MRP
      expression was found to a similar extent. Relative to the KB-3-1, cells,
      accumulation of 3H-daunomycin was reduced to 31 +/- 5% in the KB-A1 cells. In
      these KB-A1 cells, the three agents tested significantly increased the 3H
      daunomycin intracellular concentration, S9788 being the most active (311 +/- 37%)
      and inducing a near complete reversion to the basal level of the sensitive cells.
      Verapamil and PSC 833 demonstrated an additive effect (252 +/- 69% compared to
      188 +/- 33% and 126 +/- 27%, respectively). On KB-3-1 sensitive cells, S9788 had
      no effect, while verapamil or PSC 833 moderately increased the 3H-daunomycin
      accumulation, without additive effect. CONCLUSION: These results show a strong
      MDR reversing effect of S9788, which appears specific to P-glycoprotein (Pgp) and
      an additive effect between verapamil and PSC 833, suggesting a better therapeutic
      efficiency if used in well defined combinations.

PMID- 10953335
TI  - Blockade of cyclooxygenase-2 inhibits proliferation and induces apoptosis in
      human pancreatic cancer cells.
AB  - Cyclooxygenase (COX), also referred to as prostaglandin endoperoxide synthase, is
      a key enzyme in the conversion of arachidonic acid to prostaglandins and other
      eicosanoids. Epidemiologic, animal and in vitro observations show a positive
      correlation between the expression of COX (especially COX-2) and colonic cancer
      development, growth and apoptosis. Constitutive expression of COX-2 in human
      pancreatic cancer cells was recently reported. To evaluate the potential role of
      COX in pancreatic cancer, RT-PCR was used to determine the constitutive
      expression of COX-2 in four pancreatic cancer cell lines. MiaPaCa2, PANC-1, HPAF,
      ASPC-1. The effect of COX blockade with either the general COX inhibitor,
      indomethacin, or the specific COX-2 inhibitor, NS-398, on [3H]-thymidine
      incorporation and cell number was investigated in these four pancreatic cancer
      cell lines. In addition, the effects of these COX inhibitors on pancreatic cancer
      cell apoptosis was evaluated by DNA propidium iodide staining and the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      (TUNEL) assay. All four human pancreatic cancer cell lines expressed COX-2 and
      their proliferation was concentration- and time-dependently inhibited by both
      indomethacin andNS398. Substantial apoptosis was also induced by treatment of
      pancreatic cancer cells with either indomethacin or NS398, as indicated by both
      DNA propidium iodide staining and the TUNEL assay. Furthermore, indomethacin and
      NS398 were equipotent for growth inhibition and induction of apoptosis,
      indicating that eicosanoid synthesis via COX-2 is involved in pancreatic cancer
      cell proliferation and survival. In conclusion, these findings suggest that the
      COX pathway, especially COX-2, contributes to the growth and apoptosis of
      pancreatic cancer. Specific COX-2 inhibitors are likely to be valuable for the
      treatment and prevention of this deadly cancer.

PMID- 10953336
TI  - Differential TPA and PDGF-BB effects on subcellular localisation of PKC alpha and
      beta I in C3H/10T1/2 cells.
AB  - 60-75% of PKC alpha and 30-40% of PKC beta I++ protein was located to the
      membranes and nuclear/nuclear associated endoplasmatic reticulum fractions of
      resting 10T1/2CI 8 mouse embryo fibroblasts. On average, 35% of the PKC alpha and
      65% of the PKC beta I++ isoforms existed in a soluble state. Maximum PDGF-BB
      mediated Erk1 activation was obtained without significant changes in soluble PKC
      alpha- or PKC beta I++- levels. The subcellular localisation of PKC alpha and PKC
      beta I was not affected by PDGF-BB treatment. 12-O-tetradecanoyl phorbol-13
      acetate (TPA) caused translocation of cytoplasmic PKC alpha and beta I to the
      nucleus/nuclear associated endoplasmatic reticulum fraction. Down-regulation of
      PKC and bisindolylmaleimide I inhibited both TPA and PDGF-BB stimulated Erk1
      activity. We are the first to show that PDGF-mediated activation of Erk1 involves
      a PKC-dependent step in 10T1/2CI 8 cells. We also provide novel evidence that
      PDGF-BB mediated Erk1 activation can take place in these cells without apparent
      recruitment of soluble PKC alpha/beta I to the particulate cell fractions.

PMID- 10953337
TI  - 2-Methoxyestradiol blocks estrogen-induced rat pituitary tumor growth and tumor
      angiogenesis: possible role of vascular endothelial growth factor.
AB  - Natural and synthetic estrogens have been associated with several types of human
      and animal cancers including prolactin-secreting pituitary tumors in Fischer 344
      rats. These prolactin-secreting tumors are highly angiogenic and their growth is
      angiogenic dependent. In the present study we have utilized this model to
      evaluate the effect of 2-methoxyestradiol (2-ME), an endogenous estrogen
      metabolite that is a potent inhibitor of endothelial cell proliferation in vitro,
      on estrogen-induced pituitary tumor growth and angiogenesis. Adult female rats
      were implanted (subcutaneously) with a silastic capsule containing estradiol
      17beta (E2). After seven days of constant E2 exposure animals were injected (sc)
      daily with 25 mg/kg of 2-ME and killed either three or 8 days later. Changes in
      pituitary weight and proliferating cell nuclear antigen (PCNA) labeling index
      indicated growth while degree of angiogenesis was determined
      immunohistochemically using factor VIII related antigen. The results indicate
      that 2-ME inhibited estrogen-induced lactotroph growth by 32% and tumor
      angiogenesis by 89%. Furthermore, vascular endothelial growth factor (VEGF)
      expression, evaluated by immunohistochemical analysis, was down-regulated
      concomitant with tumor angiogenic suppression. These studies suggest that 2-ME
      may have therapeutic potential for hormone-induced cancer and that its
      angiostatic activity may be modulated through down-regulation of VEGF expression.

PMID- 10953338
TI  - Photodynamic action of meta-tetrahydroxyphenylchlorin (mTHPC) on an ovarian
      cancer cell line.
AB  - Meta-tetrahydroxyphenylchlorin (mTHPC) exhibits significant cytotoxicity against
      a variety of human cells in culture in combination with light, but also in dark
      reaction. The ovarian cancer cell line SK-OV3 was incubated with various
      concentrations of mTHPC and in comparison with Taxol and Cisplatin: then the
      effect on cell growth was determined. mTHPC exhibited an IC50 of 0.9 muM after 24
      hours incubation (IC50 of 1.25 after 2 hours), whereas Cisplatin and Taxol,
      which, have been used as first line agents for the treatment of ovarian
      carcinomas, inhibited cell proliferation with an IC50 concentration of 4.6 muM
      and 78 nM after 24 hours incubation, respectively. Incubation of SK-OV3 cells
      with mTHPC for 5 days resulted in cytostatic cytotoxicity at a concentration of
      0.5 muM. The photodynamic effect of mTHPC depends/among other parameters/on the
      concentration of the dye present. In combination with light (approximately 15
      J/cm2) a linear relationship between the dose of mTHPC and the amount of necrotic
      cells was observable. Higher concentrations of mTHPC caused necrosis of the
      ovarian tumor cells. The intracellular concentration of mTHPC showed a linear
      increase up to 28.6 nM (incubation concentration). In summary, these studies
      demonstrated that mTHPC exhibits potent antiproliferative activity by inducing
      necrosis after application of light. MTHPC might be a promising agent with
      cytostatic and photodynamic properties for the treatment of metastasing ovarian
      carcinomas. A sensitive PCR method was not able to show the induction of
      apoptosis in the SK-OV3 ovarian cell line. Using propidium staining, it could be
      proved that the cell death was caused by necrosis and not through apoptosis after
      irradiation with light.

PMID- 10953339
TI  - Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic
      flavonoid.
AB  - Herbal therapies are commonly used by patients with cancer, despite little
      understanding about their clinical and biological activity. We recently
      demonstrated that the herbal combination PC-SPES, which contains licorice root,
      had potent estrogenic activity in vitro, in animals, and in patients with
      prostate cancer. Licochalcone-A (LA) is one flavonoid extracted from licorice
      root with antiparasitic and anti-tumor activity, but the effect on the human
      estrogen receptor and mechanism of anti-tumor activity is unknown. Recent studies
      demonstrated that the mechanism of cytotoxic effect by some estrogens may involve
      modulation of the anti-apoptotic protein bcl-2. In the present study, we
      determined if LA had estrogenic activity, anti-tumor activity, and modulated the
      apoptotic protein bcl-2 in human cell lines derived from acute leukemia, breast
      cancer, and prostate cancer. A yeast growth-based assay under the control of the
      human estrogen receptor (hER) demonstrated that LA was a phytoestrogen. A cell
      viability assay demonstrated that LA had anti-tumor activity in all cell lines
      tested and enhanced the effect of paclitaxel and vinblastine chemotherapy. LA
      induced apoptosis in MCF-7 and HL-60 cell lines, as demonstrated by cleavage of
      PARP, the substrate of ICE-like proteases. Immunoblot analysis demonstrated that
      LA decreased the anti-apoptotic protein bcl-2 and altered the bcl-2/bax ratio in
      favor of apoptosis. In contrast, the parent compound chalcone or estradiol did
      not decrease bc1-2 expression. Therefore, these data demonstrate that LA is a
      phytoestrogen with anti-tumor activity and is capable of modulating bcl-2 protein
      expression. The modulation of bcl-2 may be dependent on specific structural
      differences between LA and the parent compound chalcone and independent of LA
      estrogenicity.

PMID- 10953340
TI  - All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene
      expression as well as telomerase activity of human medulloblastoma cells.
AB  - Leukemia inhibitory factor (LIF) is prevalently expressed in human
      medulloblastomas in vivo and in vitro. Blockage of LIF expression or biological
      function can inhibit in vitro growth and induce differentiation-like phenotypes
      of medulloblastoma cells (Med-3), suggesting a redifferentiation potential of Med
      3 cells when intrinsic dedifferentiation factor(s) is suppressed or external
      differentiation element(s) is exerted. All-trans retinoic acid (RA) can induce
      differentiation in some types of cancers but its effect on medulloblastoma cells
      has not yet been described. To address the above issues, three dosages (5, 8 and
      10 mumol/L) of RA were used to treat Med-3 cells and their effects on the target
      cells were evaluated by multiple approaches. It was found that, in addition to
      induction of morphological changes and growth inhibition, RA could repress LIF
      expression as well as the telomerase activity of Med-3 cells in time- and dose
      related fashions. Our data thus suggest that the growth inhibitory effect of RA
      on Med-3 cells may be correlated with the LIF down-regulation. Reduction of
      telomerase activity by RA indicates that this enzymatic activity is a potential
      differentiation indicator of medulloblastoma cells.

PMID- 10953341
TI  - Failure of cancer vaccines: the significant limitations of this approach to
      immunotherapy.
AB  - Immunotherapy has always represented a very attractive fourth-modality
      therapeutic approach, especially in light of the many shortcomings of
      conventional surgery, radiation, and chemotherapies in the management of cancer.
      Subsets of neoplastically transformed cells have been shown to (re-)express on
      their surface molecules which are not typically present on the surface of
      neighboring normal cells. In some instances, especially in malignant melanomas,
      cytotoxic T lymphocytes (CTLs) directed against such tumor associated antigens
      (TAAs) have been isolated. The cancer vaccine approach to therapy is based on the
      notion that the immune system could possibly mount a rejection strength response
      against the neoplastically transformed cell conglomerate. However, due to the low
      immunogenicity of TAAs, downregulation of MHC molecules, the lack of adequate
      costimulatory molecule expression, secretion of immunoinhibitory cytokines, etc.,
      such expectations are rarely fulfilled. Various approaches have been explored
      ranging from the use of irradiation inactivated whole-cell vaccines derived from
      both autologous and allogeneic tumors (even tumor cell lines), and genetically
      modified versions of such cellular vaccines which aim at correcting costimulatory
      dysfunction or altering the in situ humoral milieu to aid immune recognition and
      activation. Anti-idiotype vaccines, based on cancer cell associated idiotypes,
      have also been explored which aim at increasing immunogenicity through in vivo
      generation of vigorous immune responses. Dendritic cell (DC) vaccines seek to
      improve the presentation of TAAs to naive T lymphocytes. Unfortunately, there is
      always the possibility of faulty antigen presentation which could result in
      tolerance induction to the antigens contained within the vaccine, and subsequent
      rapid tumor progression. The theoretical basis for all of these approaches is
      very well founded. Animal models, albeit highly artificial, have yielded
      promising results. Clinical trials in humans, however, have been somewhat
      disappointing. Although general immune activation directed against the target
      antigens contained within the cancer vaccine has been documented in most cases,
      reduction in tumor load has not been frequently observed, and tumor progression
      and metastasis usually ensue, possibly following a slightly extended period of
      remission. The failure of cancer vaccines to fulfill their promise is due to the
      very relationship between host and tumor: through a natural selection process the
      host leads to the selective enrichment of clones of highly aggressive
      neoplastically transformed cells, which apparently are so dedifferentiated that
      they no longer express cancer cell specific molecules. Specific activation of the
      immune system in such cases only leads to lysis of the remaining cells expressing
      the particular TAAs in the context of the particular human leukocyte antigen
      (HLA) subclass and the necessary costimulatory molecules. The most dangerous
      clones of tumor cells however lack these features and thus the cancer vaccine is
      of little use. The use of cancer vaccines seems, at present, destined to remain
      limited to their employment as adjuvants to both traditional therapies and in the
      management of minimal residual disease following surgical resection of the
      primary cancer mass.

PMID- 10953342
TI  - Estramustine a radio sensitising agent.
AB  - The present study revealed that estramustine acts as a radio sensitising agent on
      the human renal cell cancer cell lines, A498 and CAKI-2. In vitro experiments
      used the Burker chamber technique. Both cell lines were markedly resistant to
      external beam irradiation. While pretreatment of the cell cultures with
      estramustine prior to external beam irradiation revealed an arrest of cell growth
      in both cell lines. The results of this study suggest that estramustine could be
      utilised as a radiosensitizing agent. This in turn could open a new method for
      the management of patients with advanced renal cell carcinoma (RCC).

PMID- 10953343
TI  - Effect of GM-CSF and IL-2 co-expression on the anti-tumor immune response.
AB  - We evaluated the effect of potential therapeutic genes, GM-CSF and IL-2
      respectively, or in combination of both cytokines, on the activation of systemic
      antitumor responses. CT26 tumor cells were modified to secrete GM-CSF and/or IL
      2. The growth rate of the modified tumor cells versus the parental CT26 cells did
      not show any difference. When we implanted the CT26 tumor cells which secrete
      either GM-CSF or IL-2, delayed and suppressed tumorigenicity was observed.
      However, another CT26 cell line which expresses both GM-CSF and IL-2
      (CT26/GMCSF/IL-2) did not form any tumor mass in the immunocompetent syngeneic
      Balb/c mice, showing the potential immune responses. Immunohistochemical
      examination of the modified tumor masses implanted with the cells expressing GM
      CSF or IL-2 showed increased necrosis and infiltration of NK (CD56+) lineage
      cells and macrophage/monocytes. In the vaccination model, the growth of
      rechallenged wild-type CT26 was more suppressed int he mice which were injected
      with GM-CSF or IL-2, however, the wild-type CT26 tumor formed normal tumor mass
      in the mice vaccinated with CT26/GM-CSF/IL-2 showing acute non-T-cell mediated
      immune response. As a treatment, we injected those modified tumor cells into the
      established tumor. There we could find tumor growth suppression by the injection
      of cytokine-modified CT26 cells, especially by the CT26/GM-CSF/IL-2. In the
      present study we could induce the eradication of tumorigenicity by the
      transfection of both GM-CSF and IL-2 genes and a potent role in the growth
      suppression of an established tumor.

PMID- 10953344
TI  - Detection of p53 mutations in sputum smears precedes diagnosis of non-small cell
      lung carcinoma.
AB  - Little progress has been made in reducing lung cancer mortality by applying
      conventional methods to early diagnosis and screening. Recent advances in
      molecular oncology, however, have provided tools which may be of use in this
      area. p53 gene mutation is the most common gene alteration in the development of
      lung cancer. Conventional cytologic analysis of sputum is an insensitive test for
      the diagnosis of lung cancer. In this study, we attempted to establish a
      polymerase chain reaction (PCR)-based assay for assessing the possibility of
      early detection of p53 mutation in archival Papanicolaou-stained cytologic sputum
      smears. Ten sputum smear slides were collected prior to clinical diagnosis from
      10 lung cancer patients who had been confirmed to have p53 mutations in
      surgically resected lung tumors. We successfully obtained sufficient amounts of
      RNA from each sputum smear specimen for amplification of PCR and direct
      sequencing. Only one patient was found to have p53 mutation at codon 286; the
      other nine patients had wild type p53 genes. This result supports the possibility
      that detection of p53 mutations in cytologic sputum smears is an available
      strategy for the early diagnosis of lung cancer.

PMID- 10953345
TI  - Induction of P-glycoprotein expression on the plasma membrane of human melanoma
      cells.
AB  - Melanoma cells exhibit, both in vivo and in vitro, intrinsic drug resistance to
      various chemotherapeutic agents. Cultured human melanoma cells (M14)
      intrinsically express significant amounts of multidrug resistance-related protein
      (MRP1) and P-glycoprotein (P-gp) in the Golgi apparatus, but do not express these
      drug transporters on the plasma membrane. A panel of multidrug resistant (MDR)
      melanoma cell lines (M14Dx), showing different degrees of resistance to
      doxorubicin (DOX), were isolated. In M14Dx lines, the appearance of surface P-gp,
      but not of MRP1 or lung resistance related protein (LRP), occurred in cells grown
      in the presence of DOX concentrations higher than 60 nM. Furthermore, P-gp levels
      appeared to be dose-dependent. Flow cytometry, laser scanning confocal microscopy
      and cytotoxicity studies demonstrated that the activity of the drug extrusion
      system was related to both surface P-gp expression and resistance to DOX. In
      conclusion, P-gp, but not MRP1 or LRP, might play a pivotal role in the
      pharmacologically-induced MDR phenotype of melanoma cells.

PMID- 10953346
TI  - Heat shock treated oesophageal cancer cells become thermosensitized against
      anticancer drugs.
AB  - BACKGROUND: Cancer of the oesophagus is the most common gastrointestinal
      malignancy in South African blacks. The aim of this study was to determine
      whether repetitive heat-shock (HS) treatment of oesophageal cancer cells would
      induce multi-drug resistance (MDR) as was previously found with human renal
      carcinoma cells. METHODS: The oesophageal cancer-line WHCO-3 was heat-shocked in
      sequence, on five occasions, for 90 min each at 42 degrees C, followed by a
      recovery period of 24 h between the consecutive HSs. After each shock and
      recovery period the cells were divided; one part was used for the next shock
      treatment and the other, designated the HS fraction, was used for assessments of
      drug cytotoxicity, enhanced mdr-1 and mrp gene expression by RT-PCR, and enhanced
      isoenzyme GsT-P activity. The IC50s of the drugs doxorubicin, amsacrine,
      melphalan, and cisplatin were determined after each HS using the sulphorhodamine
      B(SRB) cell-proliferation assay which was able to assess cytotoxicity. A drug
      accumulation assay was conducted by measuring 3H-Vinblastin uptake in surviving
      cells using the SRB assay to quantitate the viable cells. RESULTS: Multiple heat
      shocks did not introduce MDR via the MDR-1 or MRP mechanisms because these genes
      were not over-expressed after consecutive HS treatments. Deminished cytotoxicity
      of the drugs, as measured by increased IC50, did not occur, as it would have been
      if MDR was introduced. Therefore neither the topoisomerase drug resistant
      mechanism nor the enhanced GsT-P detoxification mechanism were introduced with
      repetitive heat-shocks. On the contrary the IC50s of doxorubucin and amsacrine
      decreased after five HSs, whereas melphalan and cisplatin, had no cytotoxic
      effects. The GsT-P levels were dramatically reduced by 90% after five HSs and an
      8 day recovery period, indicating that the cancer cells became more sensitive
      towards toxic drugs and not drug resistant as expected. However, with the drug
      influx assay the uptake of 3H-vinblastin was reduced, with each consecutive HS,
      and not reversed by verapamil thereby confirming the finding that the efflux
      mechanisms of MDR-1 and MRP were not introduced. CONCLUSIONS: Repetitive heat
      shocks did not introduce multi-drug resistance, but on the contrary, sensitized
      the oesophageal cancer cells against toxic anticancer drugs and they therefore
      became thermosensitized.

PMID- 10953347
TI  - The use of lipiodol and medium chain triglyceride as delivery agents for hepatic
      arterial administration of 1, 25-dihydroxyvitamin D3--a potential new treatment
      for hepatocellular carcinoma.
AB  - It is well established that 1, 25 dihydroxyvitamin D3 is capable of inhibiting
      the proliferation of a number of human cancer cell lines, including hepatoma cell
      lines. However, clinical usage in the treatment of cancers has been limited by
      its hypercalaemic effects. We hypothesised that by delivering 1, 25
      dihydroxyvitamin D3 dissolved in a lipid based carrier agent as a hepatic
      arterial infusion it would be possible to achieve high local concentrations
      within hepatomas for prolonged periods, whilst avoiding high systemic
      concentrations and hypercalcaemia. We examined this hypothesis by administering a
      hepatic arterial infusion of 1, 25 dihydroxyvitamin D3 in either Lipiodol, Medium
      Chain Triglyceride (MCT), or saline to hepatoma bearing rats. Assay of serum and
      tissue concentrations revealed that this approach using lipiodol or triglyceride
      results in selective distribution of 1, 25-dihydroxyvitamin D3 into, and
      retention within hepatoma tissue and low initial systemic serum levels. Lipiodol
      was more effective in these respects than MCT. This method of administration has
      potential in the treatment of hepatoma.

PMID- 10953348
TI  - Immunocytochemical detection of homeobox B3, B4, and C6 gene product expression
      in lung carcinomas.
AB  - The so-called homebox (HOX) was described as a highly conserved DNA motif of 183
      base pairs, encoding the 61 amino acid DNA-binding homeodomain. Numerous HOX
      genes have subsequently been shown to bind to DNA and regulate the transcription
      of other genes. In humans the class I HOX genes are placed in four clusters on
      different chromosomes. The order of the genes within each of these clusters is
      evolutionarily conserved to a high degree and suggests that such an organization
      may be essential in the function of these genes during normal embryo- and
      histogenesis. Re-expression of HOX gene products has been reported in a wide
      variety of neoplastically transformed cells and it seems very likely that the HOX
      genes represent yet another class of oncofetal antigens involved in both normal
      development and cellular carcinogenesis, as well as tumor progression. The
      expression pattern of three homeobox gene products (HOX-B3, HOX-B4, and HOX-C6),
      all shown to be involved in lung tissue development, was examined
      immunocytochemically, in human lung carcinoma (LC) tissues. In all observed LC
      cases, HOX-C6 was present in over 60% of neoplastic cells (+3) demonstrating a
      medium grade (B and C) staining intensity. A smaller number of neoplastically
      transformed epithelial cells also expressed the proteins HOX-B3 and -B4 (10% to
      60% or +2 to +3 and a medium grade staining intensity or B and C). The
      significance of these novel oncofetal antigens in tumor cell biology and as
      target molecules in the immunotherapy of lung carcinomas should be established by
      future studies.

PMID- 10953349
TI  - Homeobox B3, B4, and C6 gene product expression in osteosarcomas as detected by
      immunocytochemistry.
AB  - Osteosarcoma (OS) is a malignant neoplastic disease of the bone, of mesenchymal
      origin and with considerable morphologic heterogeneity, consisting of malignant
      stoma with evidence of malignant osteoid, bone and/or cartilage production. The
      mammalian homeobox (HOX) represents a highly conserved DNA motif of 183 base
      pairs, encoding the 61 amino acid DNA-binding homeodomain, through which the HOX
      gene products regulate the transcription of other genes involved in onto- and
      histogenesis. Re-expression of HOX proteins has been identified in a wide variety
      of neoplastically transformed cell types and it seems that the HOX genes
      represent yet another family of oncofetal antigens involved in both normal
      development and oncogenesis, as well as tumor tissue progression. During this
      study, the expression pattern of three HOX gene products (HOX-C6, -B3, and -B4)
      was examined immunocytochemically in human osteosarcoma (OS) tissues. In all
      observed (16/16) OS cases, HOX-C6 was present in over 90% of the neoplastically
      transformed cells (+4), demonstrating a high to medium grade (A to B) staining
      intensity. Similar results were obtained in OS cells for the other two observed
      proteins (HOX-B3 and -B4; over 90% or +4 and a high to medium grade staining
      intensity or A and B). The significance of the expression of class I HOX proteins
      in the pathobiology, diagnosis and prognostication of human OS should be
      established by further investigations.

PMID- 10953350
TI  - Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by p53 in
      a p53-null thyroid carcinoma cell line in vivo.
AB  - Our recent in vitro findings for suppression of thrombospondin-1 (TSP1; an
      antiangiogenic factor) expression by wild-type (wt) p53 in a p53-null thyroid
      carcinoma cell line, FRO, prompted us to investigate the in vivo effect of
      exogenous wt-p53 and TSP1 expression on tumor growth and angiogenesis of FRO
      xenografts in nude mice. Overexpression of TSP1, which did not affect the in
      vitro cell growth, significantly inhibited the in vivo tumor growth and
      neovascularization but not tumorigenesis; all the mice inoculated with FRO cells
      expressing TSP1 developed tumors, which were smaller and less vascularized than
      those derived from FRO cells. In contrast, restoration of wt-p53 expression,
      which reduced the in vitro cell growth rate, inhibited tumorigenesis and induced
      a state of "dormancy". Thus, approximately 40% of mice inoculated with FRO cells
      expressing wt-p53 (FRO-p53) were tumor free and the remaining mice developed
      hypovascular tumors which remained small (< or = 5 mm in size) for up to 60 days.
      Of interest, the phenotype of FRO-p53 tumors reverted to a well vascularized,
      progressively expanding tumor by exogenous expression of vascular endothelial
      growth factor (a proangiogenic factor). Our data demonstrated wt-p53 inhibition
      of tumorigenesis and induction of dormancy by suppression of neovascularization
      in FRO cells. The results suggest that p53 gene therapy for thyroid carcinoma
      harboring p53 mutation may be more efficacious than we had expected from previous
      in vitro data.

PMID- 10953351
TI  - Immune system activation by CDDP and "poly-plat".
AB  - Murine peritoneal macrophages, human fibroblasts and human ovarian
      teratocarcinoma cells were treated with CDDP (10 micrograms/ml) and "poly-plat"
      (10 micrograms/ml) for 2 h and cultured for 2-96 h. After "poly-plat" treatment
      macrophages developed cytoplasmic extensions much faster and secreted higher
      levels of interleukin-2 (IL-2), compared to CDDP. "Poly-plat" treated human
      fibroblasts demonstrated a significant release of IL-2 (138 pg/ml), compared to
      CDDP (64 pg/ml) or the untreated normal cells (31 pg/ml) after 8 h.
      Correspondingly there was a 53% increase in cells after "poly-plat" treatment
      compared to only 37% after CDDP. However, human ovarian teratocarcinoma cells
      didn't show any significant increase in IL-2 levels after "poly-plat" treatment
      and there was instead a decrease of 15% in cell numbers at 8 h. Based on our
      studies, we propose that "poly-plat" is more effective in activation of the
      macrophages and human fibroblasts in terms of IL-2, but not so with human ovarian
      teratocarcinoma cells.

PMID- 10953352
TI  - Hepatic intra-arterial injection of lipiodol-1,25-dihydroxyvitamin D3 for
      hepatocellular carcinoma in rats.
AB  - BACKGROUND: 1,25-(OH)2 D3 has an in vitro growth regulator effect on different
      cancers. Unfortunately, dose-limiting toxicity (hypercalcemia) limits its use in
      anticancer therapy. For primary liver tumors, loco-regional delivery of 1,25
      (OH)2 D3 in lipiodol might avoid high systemic concentrations and development of
      hypercalcemia. MATERIALS AND METHODS: 1,25-(OH)2 D3 alone or mixed in lipiodol,
      was delivered at different concentrations into the hepatic artery of rats bearing
      a primary liver tumor. Calcium levels, tumor volume and proliferation index were
      assessed after treatment. RESULTS: Serum calcium values were significantly lower
      when the drug was mixed into lipiodol. Treatment with 10 micrograms of 1,25-(OH)2
      D3 in ethanol resulted in a decrease in proliferation index within the tumor.
      CONCLUSIONS: The delivery of 1,25-(OH)2 D3 mixed in lipiodol reduces the
      subsequent elevation of serum calcium. Locoregional treatment with 1,25-(OH)2 D3
      was shown for the first time to be effective on primary liver tumor growth in
      vivo.

PMID- 10953353
TI  - Synergistic antineoplastic and cytogenetic effects by the combined action of two
      homo-aza-steroidal esters of nitrogen mustards on P388 and L1210 leukaemias in
      vivo and in vitro.
AB  - In order to increase the damaging effects on specific DNA sequences and decrease
      the subsequent toxicity, the use of homo-aza-steroidal esters of nitrogen
      mustards is already known. Two specific homo-aza-steroidal esters were mixed at
      different proportions and the resultant final mixtures were tested in vivo and in
      vitro. The effects of these on P388 and L1210 leukaemias, on SCE rates and on
      human lymphocyte proliferation kinetics were studied. The results demonstrate
      that the combined substances enhanced SCE induction (p < 0.05) and antitumour
      activity (p < 0.02) in a synergistic manner. A correlation was observed (p <
      0.001) between the magnitude of the SCE response and the depression of the cell
      proliferation index.

PMID- 10953354
TI  - Engineering and characterization of a single-chain antibody fragment (scFV1924)
      against the human sarcoma-associated antigen p102.
AB  - BACKGROUND: Monoclonal Antibody (MAb) 19-24 against the human sarcoma-associated
      antigen (SAA) p102 was previously characterized, and it demonstrated potential
      for sarcoma immunodiagnosis and immunotherapy. Due to the limitations of using
      intact murine MAbs in human clinical settings, we engineered a single-chain
      antibody fragment of MAb 19-24 (scFV1924). MATERIALS AND METHODS: Monoclonal
      Antibody (MAb) 19-24 against the human sarcoma-associated antigen (SAA) p102 was
      previously characterized, and it demonstrated potential for sarcoma
      immunodiagnosis and immunotherapy. Due to the limitations of using intact murine
      MAbs in human clinical settings, we engineered a single-chain antibody fragment
      of MAb 19-24 (scFV1924). RESULTS: The results from competition radioimmunoassay
      showed that binding of MAb 19-24 to SAA p102 on sarcoma cell membranes was
      inhibited by scFV1924. CONCLUSIONS: This indicates the potential of further
      application of the scFV1924 in human sarcoma immunotherapy.

PMID- 10953355
TI  - Inhibition of Ras farnesylation by lovastatin leads to downregulation of
      proliferation and migration in primary cultured human glioblastoma cells.
AB  - BACKGROUND: Malignant astrocytomas are the most common primary intracranial human
      tumors. All therapeutic approaches are limited due to their high proliferative
      capacity and their ability to diffusely invade the brain. Amplification of
      tyrosine kinase receptors and their signaling pathways have been implicated as
      contributing to the molecular pathogenesis of astrocytomas, providing possible
      new targets for therapeutic intervention. In particular, astrocytomas, although
      lacking oncogenic Ras mutations, have elevated levels of activated Ras.
      Lovastatin, an inhibitor of the beta-hydroxy-beta-methylglutary CoA reductase
      (HMG-CoA-reductase), is currently used to treat patients with
      hypercholesterolemia. In addition, it inhibits isoprenylation of several members
      of the Ras superfamily of proteins and therefore has multiple cellular effects
      including the reduction of proliferation. MATERIALS AND METHODS: In this study,
      we investigated the impact of lovastatin on two human glioma cell lines and on 15
      primary cell cultures established from biopsies of patients with glioblastoma
      multiforme (GBM,) Proliferation of glioma cell lines and primary tumor cells was
      determined by cell counting and by using the MTT assay. The cell morphology was
      analyzed by staining of actin filaments with phalloidin. Apoptosis was measured
      using the TUNEL assay. To investigate the influence of this drug on glioma cell
      motility, tumor cell migration was investigated using three dimensional spheroid
      disintegration assays. In addition, tumor cell invasion was analyzed with a
      confrontational assay between tumor spheroids and rat brain aggregates. RESULTS:
      Inhibition of farnesyl biosynthesis using lovastatin led to a block in Ras
      mediated signaling, indicated by lower MAPK activity. Consequently, tumor cell
      proliferation was reduced up to 80%. Lovastatin appeared to decrease glioma
      viability by inducing apoptosis, as indicated by morphological changes and
      increase of TUNEL positive cells. Lovastatin acts through isoprenoid depletion,
      because supplementation of the media with 50-100 microM mevalonate restored all
      tau eta epsilon effects. Invasion of tumor cells into brain tissue was not
      effected while migration was reduced beta upsilon about 30-40% in cells treated
      with high concentrations (> or = 100 microM) of lovastatin. This was surprising
      because drug treatment at lower concentrations led to a disruption of the actin
      cytoskeleton, as indicated by Phalloidin staining. CONCLUSION: Our data strongly
      suggest that inhibition of elevated Ras activity by lovastatin effectively
      targets the MAPK and probably other signaling pathways thus offering a
      pharmacological based approach for a potential treatment of human astrocytomas.

PMID- 10953356
TI  - Flow cytometric analysis of antigen expression in malignant and normal renal
      cells.
AB  - Flow cytometry allows quantitative analysis of cancer cells. The aim of this
      study was to make a quantitative study of antigen expression in malignant and
      normal renal cells in order to find the efficient monoclonal antibodies (mAbs)
      for labelling renal cancer cells. MATERIAL AND METHODS: 15 malignant and adjacent
      normal renal tissues and three renal carcinoma cell lines (ACHN, A704 and CAKI-2)
      were analyzed. The malignant and normal renal tissues were dissociated
      mechanically into cell suspension. The mAbs and isotype controls were used for
      immunochemical labelling. The stained cells were analyzed by flow cytometry.
      RESULTS: Renal tumor associated antigen G 250 was frequently detected in
      malignant renal cells but not in normal renal cells. Renal tumor associated
      antigen gp200 recognized by 66.4.C2 and PN-15 was frequently detected in
      malignant cells, normal renal cells and also in all three carcinoma cell lines.
      Epithelial antigens were strongly positive in normal renal cells. Compared with
      MOC 31, Ber-EP4 and E 29, W-lD9 was mostly reactive to malignant renal cells. VU
      1D9 was strongly positive on ACHN and A704. The carbohydrate carcinoma antigens
      CA 125, DF3 and Sialyl Lewis(a) were detectable in some of the malignant and
      normal renal cells. Sialyl Lewis(a) could be weakly detected on ACHN and A 704.
      Pan-cytokeratins and cytokeratin (CK) 8 were strongly expressed in malignant and
      normal renal cells and in all three cell lines. CONCLUSION: Our results indicated
      that G 250, 66.4.Ca, PN-15, VU-1D9, MNF116 and anti-ckg were efficient mAbs for
      labelling renal cancer cells. Their potential clinical application by flow
      cytometry should be explored.

PMID- 10953357
TI  - Growth inhibition of MCF-7 cells by estrogen is dependent upon a serum factor.
AB  - MCF-7 cell growth is normally dependent upon estrogen, but if cells are
      maintained in serum-free medium estrogen inhibits cell growth with an IC50 of
      about 1 nM. Cells adapted to serum-free medium have approximately the same levels
      of estrogen receptor mRNA as control cells that are stimulated by estrogen. We
      have identified two serum components, one estrogen dependent and one not, that
      appear to be responsible for the inhibition of growth by estrogen. Our
      observations are consistent with the presence of a plasma membrane receptor which
      negatively regulates MCF-7 cell growth, and that can be inhibited by a serum
      protein that binds estrogen.

PMID- 10953358
TI  - A steroid-binding protein mediates estrogen-dependent inhibition of growth of MCF
      7 breast cancer cells.
AB  - We have described two different proteins that mediate MCF-7 cell growth
      inhibition (1). One is estrogen-dependent and is a heterodimer consisting of a
      heavy (54 kDa) and light (29 kDa) chain. This protein is distinct from cortisol
      binding globulin (CBG), sex hormone-binding protein (SBP or SHBG) and albumin
      (HSA). It may be fetal steroid binding protein (FSBP). The other is not estrogen
      dependent, but may be related to the estrogen-dependent protein. Since these are
      large proteins they must be acting at the level of the plasma membrane, not
      traditional intracellular estrogen receptors, and inhibit MCF-7 cell growth.

PMID- 10953359
TI  - Analysis of the DNA content in the progression of recurrent and metastatic
      melanomas.
AB  - Ploidy status and ploidy related parameters of 18 primary melanomas, 32
      recurrences and 18 lymphatic metastases were investigated applying CAS200 image
      analyzer. All the tumours investigated were either suspicious for aneuploidy
      (Auer III) or clearly aneuploid (Auer IV). Primary melanomas differed from
      recurrent tumours concerning the percentage of aneuploid cells between 4c and 8c
      and 5c ER. Comparison of cutaneous tumours with lymphatic metastases showed a
      significant difference concerning the percentage of aneuploid cells between 2c
      and 4c. An already high aneuploidy rate in primary tumours suggests that
      recurrent and metastatic clones of cells are present in early stages and that
      aneuploidy status in primary melanomas could be regarded as one of the risk
      factors of recurrences and metastases.

PMID- 10953360
TI  - [History of surgical treatment of atherosclerosis of the coronary arteries--the
      first 100 years].
AB  - Atherosclerotic coronary artery disease is the most common cause of morbidity and
      mortality. The incidence of cardiovascular morbidity and mortality has been
      doubled in our country during the period 1980 through 1996. Surgical treatment of
      the atherosclerotic coronary artery disease is already a century old, ever since
      Francois-Franck (in 1899) tried to achieve sympathetic denervation of the
      cervical ganglion. After the interim period of indirect myocardial
      revascularization, during the last 30 years, direct surgical revascularization
      has reached excellent early and long-term results, and became one of the most
      frequently performed procedures in the surgical practice. Use of arterial grafts
      and, introduced recently, procedures on the beating heart, minimally invasive
      procedures and, so called, port-access procedures became a daily routine in many
      centers. Surgical revascularization of the ischaemic cardiac muscle is the
      rapidly changing entity, along with diagnostic, technical and other improvements.
      We present a brief historical overview of the efforts of cardiac surgeons to
      combat the "disease of the century" atherosclerotic coronary artery disease.

PMID- 10953361
TI  - [Idiopathic inflammatory bowel disease].
AB  - IBD (Crohn's disease, ulcerative colitis) present a great challenge to medical
      sciences because of many secrets which still hidden their real nature. Modern
      sophisticated digestive surgery occupies very important place in the treatment of
      IBD, owing to bravurous surgical skill and in a great dill to logistic support of
      different medical disciplines. Historical evaluation of scientific knowledge and
      pathways of therapeutic approaches are described. Contemporary principles and
      method of treatment are particularly stressed, especially on the surgical field.

PMID- 10953362
TI  - [Radiographic diagnosis of ulcerative colitis and Crohn disease].
AB  - Radiological diagnosis of the inflammatory bowel disease (IBD), ulcerative
      colitis and Crohns disease, is establishing by plain abdominal philm, barium
      enema study and enteroclisis. Inspite of difficult radiologic differential
      diagnosis during advanced stage of the IBD (regarding similar radiological
      signs), in the early stage of the IBD radiological diagnosis can be reached using
      regular algorithm of the investigation and knowing and recognising early signs.
      We described differential basic radiological signs of both IBD.

PMID- 10953363
TI  - [Endoscopy in inflammatory bowel disease].
AB  - Fiberoptic endoscopy is well established, safe and accurate for diagnosis and
      management of inflammatory bowel disease (IBD). Direct visualization of the
      mucosa and biopsy of suspected abnormalities are possible. The principal
      applications of endoscopy in IBD include discrimination of Crohn's disease from
      ulcerative colitis of o other inflammatory conditions (acute infectious colitis,
      chronic infections, microscopic colitis, ischemic/radiation colitis, colitis
      induced by NSAID), delineation of the sites of disease or extent, grading of
      endoscopic disease severity, and confirmation of complications such as stricture,
      fistula or mass. Finally, diagnosis of pouchitis, surveillance to detect
      precancer, or therapeutic interventions such as dilatation of strictures of
      electrocautery of bleeding sites are also important endoscopic applications.

PMID- 10953364
TI  - [Indeterminate colitis (nonspecific inflammatory bowel disease)].
AB  - Distinguishing of indeterminate colitis from ulcerative colitis or Crohn's
      disease in more than 10% of IBD cases as separate diagnostic category (IIBD) is
      defined by: first, overlapping or paucity of features of two major IBD forms in
      acute fulminant colitides and few chronic slowly progressive cases without
      differentiating markers of chronicity, and second, inability to reach specific
      diagnosis during or after completed clinical, radiological, endoscopical and
      histopathological examination of chronic colitis with inconclusive presentation
      of IBD-compatible cases. It implicates the contemporary category of IIBD, until
      some new relevant data of further clinical (preferably natural history and course
      of the disease) and histopathological examination of prior biopsies will possibly
      reclassify 20-75% of these cases into ulcerative colitis category (up to 40%) or
      Crohn's disease (up to 25%) at a median of 10 years' follow-up. The presence of
      ileal and/or perianal disease as well as later evident granulomatous and/or
      fissuring disease, including cases with pouchitis and diversion colitis in
      addition, could be helpful in favouring of Crohn's disease. Lacking specific
      signs of disease, IIBD is not a distinct entity. Still, many patients remain in
      this category. The most far is acute fulminant disease in adolescents and young
      adults with unusual distribution of transmural inflammation with deep fissuring
      ulcerations, sometimes of "collar-stud" type and normal mucosa between them,
      often with relative rectal sparing. There is significant risk of relapse and
      complications, but mild clinical course and even spontaneous regression are also
      reported. Failure of ileal pouch-anal anastomosis surgery is about 20% more
      frequent then in ulcerative colitis with overall worse prognosis in life
      expectations. Diagnostic problems and the main presentations are discussed in
      detail, as well as genetic and etiopathogenetic basis for heterogeneity of IBD.

PMID- 10953365
TI  - [Premalignant and malignant changes in idiopathic inflammatory bowel disease].
AB  - It is well known that patients with long-standing inflammatory bowel disease
      (IBD), ulcerative colitis (UC) or Crohn's disease(CD) are at increased risk for
      developing colorectal cancer (CC). Before adenocarcinoma develops, the intestinal
      epithelium progress through a premalignant phase of dysplasia, which can be
      identified via mucosal biopsy and routine tissue histology. Surveillance
      colonoscopy and prophylactic colectomy for dysplasia or asymptomatic cancer is
      advised as a method of reducing cancer-related mortality. Many physicians
      suggests that surveillance for extensive colitis should begin after 8 to 10 years
      of disease, and surveillance for left-sided colitis should begin after 15-20
      years. Colonoscopy is recommended with frequent biopsies, at least every 10 cm in
      all four quadrants, and with biopsy of any suspicious lesion. The emerging field
      of colon cancer genetics has identified several important tumor markers that have
      potential to improve sensitivity for detection of early neoplasia.

PMID- 10953366
TI  - [Pharmacotherapy of inflammatory bowel disease].
AB  - Inflammatory bowel disease (IBD) encompasses ulcerative colitis and Crohn's
      disease. Since the etiology of both diseases, is undetermined the causal therapy
      do not exist. Medical treatment has focused on nonspecific suppressions of the
      inflammatory process. There are four groups of IBD drugs: anti-inflammatory
      medicaments, immunomodulators, antidiarrheal agents, and biologic therapy. In a
      last year immunosuppressives become the very essential IBD drugs. Azathioprine is
      drug of choice for chronically active Crohn's disease; methotrexate become the
      second line immunosuppressive drug. It appears that anti-TNG monoclonal
      antibodies, cA2 (infliximab) may produce rapid control of active Crohn's disease
      and achieve tissue healing. Topically acting glucocorticosteroids are a safer
      than standard glicocorticosteroids in ileocolonic Crohn's disease. Cyclosporin is
      becoming a drug of choice in severely active ulcerative colitis. Anti
      inflammatory agents, sulfasalazine and 5-ASA drugs are recommended in treatment
      mild and moderately active IBD and as maintenance treatment in ulcerative
      colitis. Corticosteroids still have the main role in the treatment of active IBD.
      There is no convincing data for efficacy of corticosteroids as maintenance
      therapy.

PMID- 10953367
TI  - [Inflammatory bowel disease in children].
AB  - Beside Crohn's disease (CD) and ulcerative colitis (UC), paediatric chronic
      inflammatory bowel diseases encompass variety of different inflammatory
      conditions: allergic colitis in infancy, colitis of hypereosinophilic syndrome,
      Behcet colitis, microscopic colitides etc. Paediatric CD characterises
      predominance of inflammatory and obstructive disease variant. Because of their
      growth suppression an early introduction of azathioprine in steroid dependent and
      steroid refractory cases is frequently indicated. In teenage period resection
      procedures may be an elective and initial therapeutic option due to necessity of
      proper pubertal mental and physical development. Paediatric UC frequently
      manifests initially as pancolitis what indicates higher rate of colectomy rate.
      Therapy is still dispute about an optimal surgical procedure: restorative
      proctocolectomy or ileo-anal pull through techniques. Allergic colitis in infancy
      may mimic ulcerative colitis and rises a possibility of diagnostic and
      therapeutic confusions. Its treatment is strictly nutritive.

PMID- 10953368
TI  - [Toxic megacolon].
AB  - Toxic megacolon is a serious complication of inflammatory bowel disease, thus its
      prevention should be performed thoroughly. In patients with severe colitis
      refractory to maximal oral and topical therapy or who presents with toxicity,
      intravenous steroids are obligatory. If there is failure to achieve significant
      improvement within 7-10 days colectomy or treatment with intravenous cyclosporine
      or azathioprine are mandatory. In addition to maximal medical therapy as for
      severe colitis including broad spectrum antibiotics, patients with toxic
      megacolon should be kept nil per os, with small bowel decompression tube (if a
      small bowel ileus is present) and rotated into the prone or knee-elbow position
      frequently (evacuation of bowel gas). Any clinical, laboratory, or radiological
      deterioration require immediate colectomy. The duration of medical treatment of
      megacolon is controversial if no significant improvement is noted. Some experts
      support surgery within 72 hours, others take a more observing position if no
      toxic symptoms are present, but some advocate surgery within 24 hours.

PMID- 10953369
TI  - [Perianal complications of Crohn disease].
AB  - Perianal Crohn's diseases (PCD) means perianal skin lesions, affection of anal
      canal and onset of fistula-in-ano. These manifestations are present in 10-82 per
      cent of patients suffered from the Crohn's disease (CD). Fistula-in-ano is the
      most serious complications which significantly threaten a quality of life.
      Contemporary treatment of this kind of fistula-in-ano includes administration of
      immunosuppressive drugs, steroids, antimycotics and combination of enteral and
      parenteral nutrition, with long term local treatment. Successful results are
      obtained in 40-80%.

PMID- 10953370
TI  - [Surgical treatment of Crohn disease of the small intestine].
AB  - The evolution of the surgical treatment of Crohn's disease has three attainable
      aims: to be minimal, safe and therefore timely. Conservative surgery is
      increasingly the trend in surgical treatment of small-bowel Crohn's disease.
      Patients with Crohn's disease are managed non-surgically until complications of
      the disease or failure to thrive or significant side effects of medication occur,
      and then--at this point--surgery usually occurs. Once a complication has
      developed, it is not recommended to wait for this to become further complicated.
      Resectional surgery and strictureplasty for Crohn's disease of the small bowel
      are today methods of choice. Laparoscopic intestinal surgery is going to be of a
      great significance. Abdominal surgery for Crohn's disease is not curative and
      forms only part of a lifetime management of the patient.

PMID- 10953371
TI  - [Surgical treatment of Crohn disease of the colon and rectum].
AB  - Colon can be affected by Crohn's disease together with the small intestine, as a
      direct extension from the diseased ileum, as an isolated disease with "skip
      lesions" or as an specific pathological entity. Experiences in the surgical
      treatment of 28 cases of isolated Crohn's disease of large intestine during the
      period 1980-1997 are presented. The overall mortality was 21.4%, and all
      operative procedures quoted in literature were used. The most common operation
      performed was colectomy with ileorectoanastomosis, in one or two stages (24.9%).
      Crohn's disease of colon is more persistent that fatal disease. With conservative
      or carefully elected operative treatment it is often possible to maintain good
      comfort and Quality of life, with restored continuity of digestive tract, for a
      long time. According to the literature, after removing of the diseased segment of
      large intestine, the recurrences are observed in more than 60% in longer
      postoperative period requiring permanent ileostomy. These recurrences seem to be
      more dependent of the natural history of disease, than of the choice of
      operation. In spite of the progress of medical treatment, the operative
      management is necessary in more than 70%, due to various surgical complications.
      The perianal form of the disease is to be treated medically, or by sparing
      surgical procedures.

PMID- 10953372
TI  - [Surgical treatment of ulcerative colitis--"pouch" or ileorectal anastomosis].
AB  - Treatment of Ulcerative Colitis was always a challenge for a therapeutist. The
      therapy of the disease is usually conservative but when refractory or
      complications occur, surgical treatment is the only appropriate solution.
      Evolution of surgical techniques in treatment of Ulcerative colitis from bipolar
      colostomies, by-pass procedures, partial resections, colectomies,
      proctocolectomies to recent restorative procedures with the ileal-pouch and
      preservation of the continuity of digestive tract, shows the severity of the
      disease and explains the dilemmas which surgeons had in choosing the appropriate
      operation. Inauguration of ileal reservoir in late seventies, brought a new
      advancement in postoperative results measured by better function and quality of
      life. Even the ileal reservoir proved its superiority in surgical treatment of
      Ulcerative colitis, some dilemmas still persist. Should be rectum and continuity
      of digestive tract preserved by ileal-rectal anastomosis or by restorative
      coloproctocolectomy and ileal-pouch-anal anastomosis?

PMID- 10953373
TI  - [Ultrasonographic diagnosis of pancreatic diseases].

PMID- 10953374
TI  - [Metastasis of malignant melanoma in the small intestine--case report].
AB  - Small bowel metastases of the malignant melanoma are usually discovered in 2-5%
      of the patients with malignant melanoma of the skin during the life. They are
      usually being diagnosed with a complication on the small bowel, such as
      occlusion, bleeding, anemia and perforation of the intestine. Authors show three
      patients with metastases of the malignant melanoma in the small bowel, which lead
      to invagination, subocclusion and anemia due to bleeding. In all the patients,
      resection of the small bowel was performed with termino-terminal anastomosis. One
      of them lived 7, the other 4 months after the surgery and is in pretty well
      condition, while third patient was not controlled at all.

PMID- 10953375
TI  - [Occlusion of a calcified ascending aorta with a Foley catheter in aortocoronary
      bypass--case report].
AB  - Heavily calcified ascending aorta predisposes to aortic injury and distal
      embolization during total or partial cross-clamping, during the performance of
      open-heart procedures. Placement of the arterial cannula may be particularly
      difficult, occasionally virtually impossible using the standard technique, while
      placing the clamp on such aorta may be extremely risky. We present a case where
      we have used a Foley-balloon catheter to occlude the densely calcified ascending
      aorta, during a aorta-coronary bypass procedure, thus completely avoiding the use
      of the total aortic clamp.

PMID- 10953376
TI  - [Surgical treatment of rare anatomic variations and anomalies of the thyroid
      gland].
AB  - Choristoma and thyroid gland malpositions are embryonal disorders. The aim of
      this article is ten years analysis of their diagnostic and operative treatment.
      In 1425 thyroidectomies we have found: one lingual, intratracheal, intracardial
      thyroid and ovarial struma; six separated intrathoracic goitre and 10 mostly
      intrathoracaly (80%) situated goitre; 1.4% out of all. Correct preoperative
      diagnosis we have in lingual thyroid, two intrathoracal thyroid and in all mostly
      intrathoracal thyroids, and in others after histopathological examination.
      Operative approach was: collar incision with medial sternotomy in nine, collar
      incision with lateral thoracotomy in three, right thoracotomy in two, and only
      collar incision in one. There were two operative complications, one recurrent
      nerve lesion and one mediastinal haematoma. There was no hypocalcaemia and
      mortality. Thyroid gland anomalies are very rare and associated with lot of
      problems in diagnostic and treatment. In specialised institutions frequency of
      operative complications is the same like in routine thyroid gland surgery.

PMID- 10953377
TI  - Anatomoclinical significance of splenic artery anastomotic bridges.
AB  - The authors analyzed the frequency of anastomotic bridges between the terminal
      branches of the splenic artery, their location related to the splenic surface,
      length and caliber on a total of 102 autopsy specimens of human spleen and
      pancreatic tail. The methods applied were corrosion casting and postmortem
      arteriography. The incidence of cases with the splenic artery anastomotic bridges
      was 33.3%. They were located as follows: intrasplenic 25.5%, extrasplenic 4.9%,
      both intra- and extrasplenic 2.9%. The remaining two-thirds of spleens were free
      of anastomoses and thus hypothetically acceptable for partial and segmental
      splenectomy, as arterial bridges can jeopardize such surgical procedures.
      Intrasplenic arterial anastomotic bridges were of small caliber and ruled
      negligible, while the extrasplenic arterial anastomoses are of large caliber
      being of surgical importance.

PMID- 10953378
TI  - [The dedication of the bust of Dr. Vojislav Subotica].

PMID- 10953379
TI  - Apoptosis and cell death (mechanisms, pharmacology and promise for the future).
AB  - Rapidly growing body of evidence on cell death mechanisms and its disorders
      during last five years has replaced old paradigms and opened new horizons in
      medicine. Identification of different morphological and signaling aspects, as
      well as variances in requirement for energy enabled us to construct a theory of
      three main types of cell death: necrosis, apoptosis, and lysosomal cell death.
      Mitochondria, certain oncoproteins such as Bcl-2 family, and special catabolic
      enzymes participating in cellular demise might serve as targets for
      pharmacological manipulation. Upregulation or downregulation of programmed cell
      death has been implicated in ischemic, neurodegenerative, and autoimmune
      disorders, as well as in oncology and chronic inflammation. This minireview
      brings a short overview of genesis and development of theories on programmed cell
      death and apoptosis, summarizes basic relevant facts on apoptotic mechanisms and
      draws a new hypothesis on possible implication in medicine and surgery.

PMID- 10953380
TI  - Dose dependent biological effects of idarubicin in HL-60 cells: alterations of
      the cell-cycle and apoptosis.
AB  - TP-53 deficient cells of human leukaemia HL-60 die by massive apoptosis after
      treatment by high (50-100 nmol/l) doses of DNA damaging agent Idarubicin,
      regardless of the cell-cycle phase, in which they are affected. In contrary,
      after relatively low dose 10 nmol/l the cells die after cell-cycle arrest in G2
      phase. The results show, that apoptosis induced by idarubicin could appear
      independently of the cell-cycle phase and that period in which apoptosis is
      observed is related to the dose of Idarubicin.

PMID- 10953381
TI  - Hygiene in the domestic setting: the international situation.

PMID- 10953382
TI  - [The infective risk in Italy today: the role of the domestic environment].

PMID- 10953383
TI  - [Risk assessment in the domestic environment by critical point analysis. A report
      of a pilot project].

PMID- 10953384
TI  - [Cleaning in the domestic environment: the benefits and the risks].

PMID- 10953385
TI  - [The present and future of infections in the domestic environment in Italy].

PMID- 10953386
TI  - [The potential risks from an excess of hygiene in the home].

PMID- 10953388
TI  - [Radial fascio-cutaneous flap of the forearm and myocutaneous gracilis muscle
      flap in urologic surgery: surgical anatomy and techniques].
AB  - All the concepts and principles commonly espoused in plastic surgery are very
      useful in urologic reconstructive operations too. Hypospadia's repair, neo
      bladder reconstruction, microsurgery of the seminal way require as certain rules
      as an absolute respect for anatomy, sparing of the finest tissue vascularization
      and tension free sutures. Pedicled skin flaps harvesting and utilisation are
      techniques typical of plastic surgery but are also largely used in urologic adult
      and paediatric surgery. They are adopted for urethral, penile and corpora
      cavernosa reconstruction. Pedicled flaps are utilised for the closure of large
      skin defect in case of complicated wound or when an urinary fistula is present,
      especially after radiotherapy. A perfect knowledge of the flap nourishment and of
      the method of harvesting is crucial if the best results must be obtained. In our
      work we describe the surgical technique for the utilisation of gracilis muscle
      and forearm flap. Special care is taken to the anatomical description.

PMID- 10953387
TI  - [The use of disinfectants in the domestic environment].

PMID- 10953389
TI  - [Priapism: decisional algorithm. Our experience and role of sildenafil in sexual
      rehabilitation].
AB  - In this period we observed seven patients of whom four presented with low flow
      and three with high flow priapism. In two of the patients with ischemic priapism,
      simple blood aspiration from the corpora allowed for a quick detumescence, while
      in the other two cases a derivative intervention (one spongio cavernous and one
      glans cavernous) had to be performed. In all the three patients with high flow
      priapism we performed a superselective arteriography that obtained the
      visualisation of the arteriovenous fistula. These patients restarted their sexual
      activity after about three months. A six months a patient with low flow priapism
      restored sexual activity due to sildenafil 50 mg.

PMID- 10953390
TI  - [Our experience in the treatment of retroperitoneal fibrosis].
AB  - To discuss retroperitoneal fibrosis (RPF) etiopathogenesis and to report on our
      experience in the treatment of the disease. From 1977 to 1998 26 RPF patients, 15
      idiopathic (I group) and 11 secondary (II group), entered our clinic. Vascular
      risk factors of the I group were cigarette smoking (73.3%) and arterial
      hypertension (46.6%). Etiologic factors of the II group were aorta abdominal
      aneurysm (four cases), radiation therapy for female genital tract cancer (four
      case), aorto-bifemoral bypass for aorta aneurysm (two cases), retroperitoneal non
      Hodgkin lymphoma (one case). Treatment performed for idiopathic disease was
      medical in eight cases (alone in two, with endourologic measures in six) using
      corticosteroids in five and tamoxifen in three; only endourological in three and
      surgical in four (nephrectomy in two patients, ureterolysis and
      ureteroneocystostomy in one, pyeloureterolysis in one) with perioperative
      corticosteroid treatment in three cases. Treatments performed in patients with
      secondary disease were endourologic in five surgical in three
      (ureteroureterostomy, ureteroneocystostomy, pyeloureterolysis and
      pyeloreduction), medical with corticosteroids in two; one patient affected by
      perianeurysmatic fibrosis did not require any treatment because of disease's
      spontaneous recovery. Medical treatment induced symptom remission and plaque
      reduction in all patients. Surgery determined complete recovery in all patients
      except for one in whom the disease relapsed with controlateral urinary tract
      involvement. Medical RPF treatment for idiopathic or secondary disease is
      effective in the first stage. Disease management with tamoxifen is easy to
      perform, safe and effective. In the steady state of RPF the best results are
      obtained by surgery and perioperative glucocorticoid therapy reduced
      significantly fibrosis' relapse.

PMID- 10953391
TI  - [Percutaneous treatment of calculosis in caliceal diverticulosis: 13-year
      experience].
AB  - We report our experience with the composition and management of caliceal
      diverticular stones for the past 13 years at our institution. Fourty patients
      with caliceal diverticular stones were treated percutaneously at Long Island
      Jewish Medical Center. The size of the diverticula ranged from 1 to 4.8 cm, with
      a mean size of 2.27 cm. The stone size ranged from 0.2 to 4.5 cm in diameter with
      an average of 1.7 cm. Twenty patients underwent a metabolic evaluation. Follow-up
      ranged from 8 months to 140 months with a mean of 72.5 months. We achieved a
      stone free rate of 95%. All 40 patients were free of pain and infection. The
      chemical composition of stones was identified in 38 patients. Twelve patients
      were found to have mainly calcium phosphate stones, 16 mainly calcium oxalate
      stones, 7 mainly uric acid stones and 3 were found with milk of calcium in their
      diverticulum. Thirty-five patients had complete resolution of their diverticula
      with normal urograms. The remaining 5 patients had at least 50% diminution of the
      diverticulum size. No one of the latter patients was found to have stone
      recurrence. Metabolic evaluation of the 40 patients showed in the 75% of the
      cases any metabolic abnormality, an absorptive hypercalciuria type II in two
      patients (10%), hyperuricosuric hypercalciuria in two cases (10%) and
      hyperoxaluria in one (5%). Percutaneous management of caliceal diverticular
      stones is a safe and effective modality compared to the existing alternative
      procedures reported in the literature.

PMID- 10953392
TI  - [Clinical and sperm follow-up after subinguinal varicocelectomy].
AB  - In order to evaluate the sperm output and the adverse-side-effects after
      subinguinal varicoceloctomy, a follow-up study of 16 months was performed on 196
      selected patients (aged from 22 to 43 years) affected by left varicocele (VR). In
      the pre-treatment, both Doppler ultrasonography and didymo-epididymal
      ultrasonography allowed to distinguish two homogeneous patient groups: group A
      (no. = 136), including patients affected by VR alone and, group B (n. = 60),
      including patients with VR combined to coincidental didymo-epididymal
      morphological abnormalities, DEMA). These DEMA lesions (testis size < 12 ml,
      epididymides abnormalities: increased head- > or = 12 mm- and/or tail- > or = 6
      mm-diameter, multiple microcysts, large idrocele) were omolaterally to VR in
      30/60 (50%), eterolaterally in 19/60 (31.7%) or bilaterally in 11/60 (18.3%).
      During sperm follow-up, group A patients showed both a significant temporal
      change (p < 0.01 ANOVA) of all sperm parameters studied (sperm density, total
      sperm count, motility and morphology) from month 8 onward and sperm values
      significantly higher than found in group B patients. On the contrary, the sperm
      parameters of group B patients did not change significantly during the follow-up
      observations. As far as the varicocelectomy-mediated clinical symptoms, some
      patients complained early and transiently (on 1-2-4 weeks following
      varicocelectomy) the following symptoms: didymal pain (1.5%), didymo-epididymal
      pain (4.1%) and parasthesiaes on the anterior-medial side of the left thigh
      (4.1%) or scrotal (3.1%); only four patients (2%) complained permanent
      paresthesiaes on the anterior-medial side of the left thigh. Furthermore, the
      clinical follow-up also revealed a low rate of complications: persistent VR
      (3.6%), hydrocele (1.5%), intrascrotal venous ecstasies (6.1%), epididymitis
      (0.5%). Some morpho-structural abnormalities at US scans were transient (1-2
      weeks): scrotal oedema (6.1%), orchitis (2%), orchi-epididymitis (1%).
      Subinguinal varicocelectomy performed on large population demonstrated a
      significant improvement of the sperm output from month 8th onward in patients
      with VR alone, while sperm parameters did not show any significant change in
      patients with VR plus coincidental DEMA. This surgical technique also
      demonstrated safety since both low rates of symptoms and (transient)
      complications were registered.

PMID- 10953393
TI  - [Bladder and cavernous contractility and relaxation among intracellular
      messengers, changes in sarcoplasmatic free calcium and phosphodiesterase
      activity].
AB  - During the last decade, the cellular pathways involved in excitation-contraction
      coupling have been identified and explained. The key event in the initiation of
      the contraction is the rise in sarcoplasmic free calcium. Inositol 1,4,5
      triphosphate (IP3) and cyclic nucleotides (cAMP, cGMP) have been demonstrated to
      be the second messengers associated with stimulation of smooth muscle selective
      receptor-subtypes (cholinergic, adrenergic, non adrenergic-non cholinergic) by
      specific neuromodulators. Furthermore, activation of voltage-gated L type- or
      receptor operated calcium channels is involved in the sarcoplasmic free calcium
      changes. KCa and KATP-channels play an important role in smooth muscle
      hyperpolarization; KATP-openers excite great interest as therapeutic agents for
      the detrusor instability. The specificity of different receptor subtypes and
      their transductional pathways has increased the number of targets for drug
      treatment of urinary bladder disorders and erectile dysfunction. As the level of
      intracellular nucleotide second messengers can be modulated by tissue-specific
      phosphodiesterase (PDE) isoenzymes, PDEs selective inhibitors have the potential
      to exert organ-specific therapeutic effects. So, PDE I selective inhibitor
      vinpocetine has been proposed for the symptomatic treatment of detrusor
      instability; PDE V selective inhibitor sildenafil, enhancing the NO-cGMP pathway
      mediated cavernosal smooth muscle relaxation, is an effective drug to treat
      erectile dysfunction.

PMID- 10953394
TI  - [Unusual case of calcified renal fibroma].
AB  - The renal fibroma is an extremely rare event that takes its origin from
      parenchima, from the peri-renal tissues or from the renal capsule. A case of
      renal fibroma of a rarely met medullary origin is described.

PMID- 10953395
TI  - Bladder leiomyoma: a rare cause of urinary stress incontinence.
AB  - Lejomyoma of the bladder is an uncommon lesion and usually present as small
      intramural or submucosal lesions. Preoperative evaluation based on careful
      physical and radiologic examinations must rule out malignant and other lesions.
      It is readily and successfully treated in most cases with transurethral or open
      resection. The prognosis of this tumor is excellent and no malignant degeneration
      has been reported. The most common presentations are obstructive voiding
      symptoms, irritative symptoms, and hematuria. Occasionally, it may be a cause of
      urinary stress incontinence. Although this condition is rare, it should be
      considered in the causes of urinary stress incontinence.

PMID- 10953396
TI  - Primary molar vital pulp theory.

PMID- 10953397
TI  - Primary molar vital pulp theory.

PMID- 10953398
TI  - Gale injuries.

PMID- 10953399
TI  - Pre-definitive treatment: rehabilitation prostheses.

PMID- 10953400
TI  - Chemochemical caries removal: a review of the techniques and latest developments.
AB  - Chemomechanical caries removal involves the chemical softening of carious dentine
      followed by its removal by gentle excavation. The reagent involved is generated
      by mixing amino acids with sodium hypochlorite; N-monochloroamino acids are
      formed which selectively degrade demineralised collagen in carious dentine. The
      procedure requires 5-15 minutes but avoids the painful removal of sound dentine
      thereby reducing the need for local anaesthesia. It is well suited to the
      treatment of deciduous teeth, dental phobics and medically compromised patients.
      The dentine surface formed is highly irregular and well suited to bonding with
      composite resin or glass ionomer. When complete caries removal is achieved, the
      dentine remaining is sound and properly mineralised. The system was originally
      marketed in the USA in the 1980's as Caridex. Large volumes of solution and a
      special applicator system were required. A new system, Carisolv, has recently
      been launched on to the market. This comes as a gel, requires volumes of 0.2-1.0
      ml and is accompanied by specially designed instruments.

PMID- 10953401
TI  - The human transmissible spongiform encephalopathies (TSEs): implications for
      dental practitioners.
AB  - Transmissible spongiform encephalopathies (TSEs) are rare, fatal degenerative
      brain diseases which affect humans and certain animals, and are caused by
      inheritance or acquisition of prions (PrPs). Inherited TSEs include Fatal
      Familial Insomnia (FFI), Gerstmann-Straussler-Scheinker syndrome (GSS) and other
      less well clinically characterised disorders, while the human infective TSEs
      include sporadic, iatrogenic and variant Creutzfeldt-Jakob disease (vCJD). The
      causative prions are found especially in neural tissues and spinal fluid, and in
      the case of vCJD, in lymphoreticular tissue. Available epidemiological evidence
      suggests that normal social or routine clinical contact with affected patients
      does not present a risk to health care workers, relatives or the community.
      Isolation of patients is not considered necessary. Nevertheless as the prions are
      resistant to conventional chemical, irradiation and heat sterilisation methods,
      highly specific cross-infection control measures are required for the dental
      management of patients with, or at notable risk, of TSE. The present article
      reviews current knowledge of the clinical consequences of prion disease and
      provides information regarding necessary changes to the cross-infection routine
      when managing patients infected, or at risk of, prion disease.

PMID- 10953402
TI  - Alcohol, tobacco and paan use and understanding of oral cancer risk among Asian
      males in Leicester.
AB  - OBJECTIVES: To determine use of alcohol, tobacco and paan among males from the
      various Asian communities in Leicester; and assess their knowledge and attitudes
      towards oral cancer risk factors and prevention. Also, to determine any
      differences regarding habits and attitudes between first and second generation
      Asians. DESIGN: Volunteers completed a confidential, bilingual questionnaire
      regarding alcohol, tobacco and paan use and also knowledge about oral cancer risk
      factors and preventive measures. SETTING: Participants were recruited from
      sources that included GPs' surgeries, sixth form colleges and places of worship.
      SUBJECTS: Asian males, i.e. those of Indian, Pakistani, Bangladeshi or Sri Lankan
      origin; over the age of 16 years and resident in Leicester. MAIN OUTCOME
      MEASURES: Quantitative figures were obtained from the questionnaires as to the
      frequency of alcohol, tobacco and paan use and responses regarding oral cancer
      knowledge, risk factors and preventive measures. RESULTS: The principal Asian
      community groups in Leicester were Hindu, Sikh, Muslim and Jain. Significant
      differences were found in males from these groups with regards to habits and oral
      cancer awareness. Muslim males use tobacco and paan more than the other groups
      but avoid alcohol. Sikh males drink more alcohol (especially spirits) than the
      other groups but their use of tobacco and paan is low. Habits of Hindu and Jain
      males are variable. However, approximately 10% of both 1st and 2nd generation
      Hindu males combine all three habits of alcohol, tobacco and paan; and are thus
      considered to be at high risk of developing oral cancer. Seven percent of 1st
      generation Hindu males were found to chew paans containing tobacco which are
      strongly associated with oral cancer. More 2nd generation Jains drank alcohol
      than the 1st generation, and a greater proportion of Hindu, Sikh and Jain 2nd
      generation males drink spirits than their older counterparts. Knowledge of oral
      cancer risk factors and preventive measures were variable, the lowest level of
      knowledge being among the 1st generation Sikh group. Few volunteers realised the
      risk of alcohol drinking in the aetiology of oral cancer. CONCLUSION: The 'Asian'
      community in Leicester is not homogeneous, but consists of distinct community
      groups; each with their own cultural beliefs, habits and attitudes. Knowledge of
      these differences can be used to provide appropriate health education programmes
      suitably targeted to reduce the use of the known risk factors for oral cancer.

PMID- 10953403
TI  - Direct access day case oral surgery.
AB  - OBJECTIVE: To compare the effectiveness of direct access referrals with standard
      letter referrals, and also assess the impact of the direct access system on the
      primary care provider, secondary sector and from the patients perspective.
      DESIGN: Surgical and anaesthetic guidelines were agreed and 12 general dental
      practitioners were recruited to participate in the study. Each practitioner was
      given 100 envelopes which contained randomly allocated 50 direct and 50 standard
      referrals. For direct referrals, GDPs completed a pre-operative assessment and
      obtained an operation date by telephone from the day case unit while the patient
      was in the surgery. The clinical history sheet was faxed to the day unit and the
      radiographs posted. The only contact the patient had with the hospital was on the
      day of surgery. Standard referral patients were referred in the traditional way
      with a referral letter being sent to an out-patient clinic. Evaluation of the
      effectiveness of the direct referral system versus standard letter method were
      made via completion of questionnaires by the patients, dental practitioners,
      hospital clinicians, day case anaesthetist and co-ordinator. SETTING: The study
      was carried out over 2 years commencing in 1997 at the Oral Surgery Day Case Unit
      at Manchester Royal Infirmary. RESULTS: A greater number of direct access
      referrals (409; 90%) were treated in comparison with (312; 75%) standard
      referrals (P < 0.001). Eighty nine per cent of direct access records were
      adequate pre-operatively. More than 70% of dentists and hospital clinicians
      preferred the direct access referral method. Sixty-three per cent of standard
      letter patients were satisfied with their mode of referral compared with 87% of
      direct access patients. CONCLUSIONS: Given appropriate guidelines dental
      practitioners are able to refer directly to oral surgery day case operation
      lists. This has proved to be the favoured method of referral for dental
      practitioners, the secondary sector and patients.

PMID- 10953404
TI  - [The human genome--chromosome 22].
AB  - Once dare, today casual, the project of the human genome basic structure analysis
      celebrated its first major accomplishment when the almost complete sequence of
      the twenty-second chromosome was published. Though the chromosome represents only
      hardly more than 1.5% of the total genomic DNA, it is comparatively rich from the
      point of gene content (545 hitherto identified gene sequences) and it is
      important from the medicinal point of view. Among pathologic states resulting
      from its impaired function inborn heart and major vessel defects, mental
      disorders, and malignities are rated.

PMID- 10953405
TI  - [Antioxidants and protection of the skin against the effect of ultraviolet rays].
AB  - Ultraviolet radiation causes increase of production of the reactive oxygen
      species in the human skin, which are responsible for oxidative stress and damage
      of many important cellular components in the target tissue. The complex of
      antioxidants represents the major protective system against the oxidative damage
      of the skin. Many antioxidants, namely vitamin E, can be successfully used in
      photoprotection.

PMID- 10953406
TI  - [CD4 lymphopenia and postoperative immunosuppression in cardiac surgery].
AB  - The diversity and heterogeneity of biologic reactions is a condition sine qua non
      for the adaptation of live organisms to changes of external environment.
      Reactions of the immune system enable survival even in extreme conditions. Modern
      medicine often reaches situations never met by the organism in phylogenesis.
      Thanks to up-to-date therapeutical approaches many patients survive with grave
      symptoms such as multiple organ failure and extensive forms of injury. New
      infectious diseases are emerging, e.g. HIV/AIDS. Notwithstanding the broad array
      of external insults, it becomes obvious that organisms mobilize defence reactions
      according to a general scheme. Likewise, exhaustion of the immune potential
      occurs according to an archetypal pattern. In the case of cell-mediated immunity
      the faultless course of which is of critical importance for organisms in extreme
      conditions, the loss begins with the absence of reactivity of T-cells to specific
      antigens to end with the absence of their reactivity to polyclonal mitogens. The
      article deals with pathogenic mechanisms underlying the onset of
      immunodeficiencies caused by both infectious and non-infectious stimuli with
      special regard being focused on cardiac surgery in extracorporeal circuit.

PMID- 10953407
TI  - [Fenofibrate 250 SR Pharmavit in patients with mixed hyperlipoproteinemia.
      Results of a study of 189 patients from 13 centers in the Czech Republic].
AB  - BACKGROUND: Hyperlipoproteinemia represents one of the major risk factors in the
      early atherosclerosis manifestation, namely in the ischaemic heart disease. In
      patients after the myocardial infarction, mixed hyperlipoproteinemia becomes the
      most frequently diagnosed impairment of the lipid metabolism. In the therapy,
      fibrates begin to play an important role. A new remedy containing micronised
      fenofibrate (Fenofibrate 250 SR Pharmavit) was recently registered for the Czech
      market. The aim of our study was to test its effects in almost 200 patients with
      mixed hyperlipoproteinemia. METHODS AND RESULTS: Into statistical analysis of the
      treatment effectiveness 187 persons (115 males, 72 females) were included. Other
      characteristics of the studied group (mean +/- SD): age 54.0 +/- 10.7 years,
      stature 172.0 +/- 8.7 cm, weight, BMI 28.0 +/- 3.1. Prevalence of risk factors
      and clinical manifestations of the atherosclerosis: ICHS 18.2%, myocardial
      infarction 7.5%, ICHDK 4.3%, CMP 5.3%, smoking 27.8%, arterial hypertension
      63.6%, diabetes mellitus 17.6%, positive family history in ICHS 50.3%. 44.9%
      persons had been treated with hypolipidemics. Basic parameters of the lipid
      metabolism, cholesterol, LDL and HDL cholesterol and triglycerides were studied.
      Plasma levels of uric acid, fibrinogen, glucose and other biochemical parameters
      were also used to monitor the safeness of the treatment. Cholesterol
      concentration (7.05 +/- 0.91 mmol/l) decreased (6.14 +/- 0.89 mmol/l) almost by
      15%. Triglyceride concentration decrease (from 4.43 +/- 1.84 mmol/l to 2.64 +/-
      1.34 mmol/l) was more intensive (41%). HDL-cholesterol increased by almost 15%,
      while LDL-cholesterol decreased by 12%. Statistically significantly decreased
      level of the uric acid (12%), fibrinogene decrease (8.4%) reached only marginal
      significance. Treatment was well tolerated, only in one patient it was necessary
      to cut it prematurely. CONCLUSIONS: According clinical tests which included
      almost 200 patients with mixed hyperlipoproteinemia, Fenofibrate 250 SR Pharmavit
      stands for an effective and well tolerated hypolipidemics.

PMID- 10953408
TI  - [Rheological properties of blood during pulsatile pharmacomechanical and
      continuous local thrombolysis].
AB  - BACKGROUND: The aim of the work was to find out whether the controlled
      administration of a thrombolytic directly into the arterial occlusion could
      prevent formation of the systemic lytic state, which may result in distant
      bleeding complications. METHODS AND RESULTS: In patients subjected to pulsatile
      pharmacomechanical (94 patients) and local continual thrombolysis (74 patients)
      changes in blood and plasma viscosity, coagulation tests, fibrinogen levels and
      some other parameters were investigated. CONCLUSIONS: Pulsatile
      pharmacomechanical thrombolysis, similarly to other forms of thrombolysis, is
      accompanied with systemic lytic state and the risk of unwanted resorption of the
      hemostatic thrombosis. Urokinase administration brings about regress of systemic
      changes, which is similar to the use of either tested thrombolytic
      administration. As treatment by the continual thrombolysis takes is approximately
      40 times longer, the risk of systemic lytic state and bleeding complication
      growths.

PMID- 10953409
TI  - [Secondary hemophagocytic syndrome in a systemic disease].
AB  - 20 year old man 2 years treated for the seropositive rheumatoid arthritis was
      admitted for fever accompanied with jaundice, anemia and leukopenia. The
      underlying disease has been compensated already for long period of time, before
      his admission only Prednisone (in the dose of 5 mg daily) and Methotrexate (15 mg
      once a week) was given. His physical examination of admission was without any
      significant abnormalities, out of the routine laboratory examination the value of
      leukocytes count was 2.1 x 10(9)/L, erythrocytes 3.7 x 10(12)/L, hemoglobin 95
      g/l, hematocrit 0.29, platelets 156 x 10(9)/L. Since admission to hospital the
      hepatic enzymes ALT, AST, GMT, ALP were about ten times elevated comparing to
      normal values, the coagulation examination has shown the decrease of Quick test
      to 55%. With respect to the permanent leukopenia the bone marrow aspiration was
      taken with the finding of the increase number the RES elements (18.4%) with the
      signs of hemophagocytosis. The phagocytic reticulum absorbs blood elements
      erythrocytes, normoblasts, granulocytes, platelets. According to the literature
      experience we started the combination of the immunosuppressive treatment
      consisting of corticosteroids and Cyclosporine. Already the day following the
      application of the high dose of corticosteroids the fever subsided, icterus went
      away gradually with the normalization of the liver tests. After 20 days of
      hospitalisation the patient was discharged in good shape. Now, after 4 months the
      is stabilized on the follow-up treatment of Prednisone a Cyclosporine.

PMID- 10953410
TI  - [Tuberculosis in the Czech Republic in 1998].
AB  - In Czech Republic (CR) the epidemiological situation in tuberculosis (TB) was
      evaluated in 1998 using the notification TB into the TB register. 1805 new TB
      cases and relapses were notified (17.5/100,000 citizens). Majority TB cases, 1535
      (14.9/100,000 citizens) were of the respiratory system and 270 TB cases were in
      other localized Two thirds (988 cases = 9.6/100,000 citizens) of the respiratory
      system TB, were bacteriologically verified thereout 564 direct smear positive.
      Patients with lung TB only were 10% less frequent than those with respiratory
      system TB. 69 TB cases were identified in foreigners. Relapse of TB was found in
      66 patients. Among the notified TB cases were 62.9% of males and 37.1% females.
      In both sexes patients over 70 predominated. In the medium age category males
      also prevailed. Due to subjective troubles of patients TB was passively
      identified in 72.2%, actively by the physician 12.9% were identified. Late TB
      diagnosis during section occurred at 5.4% of patients. During the last 9 years
      annual number of notified patients has not changed. Only the number of
      bacteriologically verified cases of the respiratory system TB decreased and
      number of not verified cases increased. Decease due to TB was notified in 73
      (0.7/100,000 citizens) usually old patients. In 67 patients TB was diagnosed
      premortally or at section. Differences in TB prevalence were found in different
      regions. Higher numbers of the TB patients than in average for the whole state
      were found in Prague, northern and western Bohemia and in northern Moravia. 112
      new cases and relapses of MOTT were reported in 1998. Notification of TB in CR
      was on a good level. State of TB morbidity was stabilised and under control.
      However, the decrease of numbers of bacteriologically verified cases and increase
      of not verified ones, causes of occurrence of microscopically positive diseases
      will be necessary to analyse and groups which will require higher dispensary care
      have to be recognised.

PMID- 10953411
TI  - [Hematopoietic stem cell transplantation in autoimmune diseases in rheumatology
      practice].
AB  - Autoimmune diseases (AID) result from the impairment of the effector and/or
      recognition phase of the immune response. The autoimmune process plays a crucial
      role in the pathogenesis of the systemic lupus erythematosus (SLE), systemic
      sclerosis (SSc), rheumatoid arthritis (RA), and their treatment is therefore
      largely based on immunosuppression. However, some patients do not respond to its
      standard doses. The disease becomes intractable with the survival rate comparable
      to that of some haematological malignancies, or patients become soon handicapped
      with very poor quality of life, depending on continual administration of high
      doses of steroids. The new hope for those patients becomes therapy with high dose
      myelo- and immuno-ablative chemotherapy with autologous hematopoietic progenitor
      cell support (PBPC). Tens of patients with intractable forms of AID were
      transplanted in the pilot clinical studies with promising results. The most
      frequent indications included: SLE, SSc, and RA. Final conclusion of the
      therapeutic effects will be drawn from the analysis of larger trails.

PMID- 10953412
TI  - [The interphase fluorescence in situ hybridization (I-FISH) technique in patients
      with chronic lymphatic leukemia (CLL)].
AB  - BACKGROUND: Trisomy 12 was found to be the most frequent chromosomal aberration
      identified by conventional cytogenetic studies of bone marrow cells and
      peripheral lymphocytes of patients with CLL. Molecular-cytogenetic techniques
      which enable examination of dividing and/or non-diving interphase nuclei (I
      FISH), proved existence of other chromosomal abnormalities, mainly deletions,
      which could have in CLL patients relation to the origin, course and prognosis of
      the disease. METHODS AND RESULTS: During the last two years bone marrow
      chromosomes of all patients with CLL were examined by G-banding and by I-FISH.
      The numerical changes of chromosome 12 were followed by centromeric DNA probe in
      dividing and non-dividing cells. The small deletions were ascertained by locus
      specific probes for 13q14 (Rb gene), 17p13 (p53 protein) and 11q23 (MLL gene).
      These genes are responsible for cell division and their function is probably in
      connection with neoplastic process. It is of interest whether numerical and
      structural chromosomal rearrangements are primary or secondary changes and what
      is their impact on etiology of CLL. 93 patients were examined by DNA prove CEP12
      and trisomy 12 was found in 24 of them (25.8%), the range of the clone was 2.5
      75.5% of the screened cells. Deletion del(13)(q14) was examined by probe D13S319
      in 73 patients and proved in 24 of them (32.8%), pathological clone ranged 2.5
      80.0% of the cells. Deletion del(17)(p13) was found in 14 patients out of 61
      examined by probe LSI p53 (22.9%). The extent of the clone was 2.5-34.0% of
      examined cells. Deletion 11q23 was not ascertained in any of 11 patients by means
      of probe LSI 11q23 (MLL). All probes used for FISH were manufactured by VYSIS.
      CONCLUSIONS: FISH is very sensitive method, suitable for molecular-cytogenetic
      examination of leukemic patients. With I-FISH the deletion of 13q14 was
      ascertained as the most frequent chromosomal aberration in series of 73 patients
      with CLL. We continue to increase the number of patients screened by I-FISH with
      all eligible DNA probes and start the prospective study on patients with
      chromosomal pathology. We will correlate the immunophenotype, morphology,
      clinical course and prognosis with karyotypic findings.

PMID- 10953413
TI  - [Prevalence of obesity, hypertension and smoking in patients with the sleep apnea
      syndrome--comparison with the Czech population].
AB  - BACKGROUND: Sleep apnoea syndrome (SAS) is an serious disease increasing
      morbidity and mortality. SAS is often associated with cardiovascular diseases.
      This retrospective study is focused on the prevalence of selected risk factors of
      ischemic heart disease. METHODS AND RESULTS: The comparison of BMI, prevalence of
      obesity, hypertension and smoking was performed in 356 patients with SAS (287
      men, 69 women, age 25-64 years) and 2353 persons--representing 1% of Czech
      population (WHO project MONICA). T-test was used for statistical analysis of BMI
      and chi-square test for obesity, hypertension and smoking prevalence. Groups of
      patients and the MONICA group were stratified by age into 4 subgroups.
      Statistical significant difference was found in BMI and obesity prevalence in men
      in all age subgroups. Men aged 35-64 years differed in systemic hypertension
      prevalence (p < 0.001) and in age subgroups of 45-64 years in smoking prevalence
      (p < 0.001). Females aged subgroups of 35-54 years differed significantly in BMI
      (p < 0.001) and in age subgroups of 45-54 years in hypertension (p < 0.01).
      CONCLUSIONS: Higher prevalence of obesity, hypertension, and smoking were found
      in patients with SAS compared to non-selected Czech population.

PMID- 10953414
TI  - [Nitrates in cardiology practice].
AB  - Nitrates have been applied in cardiology over one hundred years. They act via
      nitric oxide release. Nitric oxide is the same substance as endogenous
      endothelium-derived relaxing factor (EDRF). The most frequently used nitrates are
      nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate and similarly
      acting moledidomine. The wide range of actions results in antiischemic and
      antianginal effect. The inhibition of platelet a aggregation is important as
      well. Nitrates have no significant adverse effects. They are used in symptomatic
      treatment of nearly all forms of coronary heart disease. They improve prognosis
      of patients with heart failure and have favourable effects on early and late left
      ventricle remodeling post myocardial infarction as well as on incidence of silent
      ischemia. Nitrates are used both for acute (short-term) and for long-term
      therapy. The may latter lead to development of tolerance, which can be prevented
      or reversed with intermittent-dosing regimens.

PMID- 10953415
TI  - [Re the article by Dr. J. Lachmanova: Dialysis therapy in the Czech Republic in
      1998 and in the future].

PMID- 10953416
TI  - [DNA methylation and neoplasms].
AB  - DNA methylation and acetylation of histone proteins represent two global
      mechanisms controlling the gene expression. DNA methylation profiles alter during
      the development of the organism and during progression of neoplasia. Three types
      of alterations of the DNA methylation profiles were observed in the tumor cells:
      hypomethylation, hypermethylation and the loss of imprinting. Beside the intra
      gene mutation and the heterozygosity absence, DNA methylation can be understood
      as the third mechanism of tumor-suppressor gene inactivation in the genesis of
      neoplasia. Our review article brings recent findings and hypotheses on the role
      of DNA methylation in the carcinogenesis and its possible application in the
      diagnostics and therapy of the malignant proliferation.

PMID- 10953417
TI  - [Endothelial reactions to hypoxia].
AB  - In the last decade endothelium was shown to play an active role in regulating
      vascular homeostasis. This review focuses on the endothelial reactions during
      pathological condition of hypoxia. Cascade of events leading to endothelial
      activation/dysfunction during hypoxia is described and consequences of our
      expanded understanding of vascular biology for current clinical practice are
      summarised.

PMID- 10953418
TI  - [Determinants of interest in primary preventive screening].
AB  - BACKGROUND: Primary prevention care requires active approach not only from the
      health professionals but also from all individuals of the target population.
      People themselves have to be interested for their own health, for the preventive
      examinations, for their life-style. However, the health supporting activities
      based on the voluntary interest are most frequently exploited by people who
      actually do not need it, and people of the high risks stay apart. The aim of the
      study was to identify major differences among those who are interested in the
      preventive examinations and who are not, and answer the question whether those
      who declare their interest are the needful and primarily aimed population.
      METHODS AND RESULTS: Within the preventive project, 4353 parents of school-aged
      children in Brno were examined using a special questionnaire. Beside interest in
      examination, following criteria were questioned and analysed: age, education
      level, economical standard, subjective evaluation of health, occurrence of
      concrete health problems, family health history, adequacy of the body weight
      (according reported height and weight), dietary habits, alcohol consumation,
      smoking habits, recreation-sport activities, and selected subjective perceptions.
      Differences based on concern about examination were evaluated by the comparison
      of studied parameters in groups formed according the "interest" and also using
      the logistic regression analysis. We found that the dominating determinant of
      concern about the preventive examination was the interest of the family partner
      (harmony of interests). In the group of persons who declared their "interest",
      higher education level, worse subjective evaluation of health, higher occurrence
      of concrete health problems, and higher incidence of selected diseases in the
      family were more frequently reported. Obversely, the number of smokers was lower
      in this group. Incidence of overweight persons differed according to their sex-
      meanwhile more overweight women were among the "interested group", more
      overweight men were among the "not interested". Women in the "interested" group
      consumed alcohol less frequently, men in this group were often more active in
      sports. Dietary habits as well as economical standard did not differ among the
      two groups. CONCLUSIONS: Though the differences among groups with different
      concern about examination were statistically different, they were not very
      pronounced. It cannot be confirmed that the preventive examination is exploited
      preferably by people without major risk factors, those socio-demographically or
      otherwise specific, or generally those to whom the proposal of examination was
      not aimed.

PMID- 10953419
TI  - [Determination of intracellular molecules in cells in hematopoietic malignancy
      using flow cytometry].
AB  - BACKGROUND: Detection of membrane molecules by immunophenotypisation is a routine
      counterpart of the laboratory tests which are needed for the complex diagnostic
      procedures of hematopoetic malignancies at present. The immunochemical detection
      of intracellular molecules is essential in such cases, where the expression of
      surface molecules on malignant cells is poor, or where the results of other
      diagnostic analyses are unequivocal (cases with ectopic expression of other
      lineage-specific molecules and cases of biphenotypic leukemias). METHODS AND
      RESULTS: We followed the procedure using 4% solution of paraformaldehyd in
      phosphate buffered saline for fixation of cells. Lysing solution G (Becton
      Dickinson) was used for permeabilisation of cells to detect nuclear and
      cytoplasmatic molecules. The permeabilised cell suspension was than washed with
      0.5% solution of Tween 20 in phosphate buffered saline. This simple and rapid
      procedure is readily available for the routine detection of intracellular
      molecules. This approach is important for the diagnosis of hematopoetic
      malignancies.

PMID- 10953420
TI  - [Microcirculation in the skin of the upper extremities in type 1 diabetics using
      the laser doppler method].
AB  - BACKGROUND: Diabetic microangiopathy is a very frequent complication of both
      types of diabetes mellitus. Detection of early microcirculation impairment may
      identify patients at high risk of severe complications and may have a great value
      for prevention of these complications. The aim of the study was to evaluate the
      skin microcirculation in upper extremities in Type 1 diabetic patients and in
      healthy volunteers with laser Doppler technique. Parameters of microcirculation
      were compared between these two groups and with diabetes control expressed by
      glycated hemoglobin, fructosamin and fasting glycaemia. Relationship between
      perfusion parameters, the age of patients and the duration of diabetes was
      analysed as well. METHODS AND RESULTS: Thirty-eight Type 1 diabetic patients (18
      men, 20 women) and twenty-six healthy persons (16 men, 10 women) were evaluated
      in this study. Differences of high statistical significance in many parameters of
      perfusion were found between these groups. A significant negative relationship
      was found between the percentage perfusion increase during postocclusive
      hyperaemia in forearm and HbA1c and fructosamine (r = -0.52, p < 0.001 and r = 
      0.47, p < 0.01, respectively), between percentage perfusion increase during local
      hypertermia and HbA1c (r = -0.47, p < 0.001). Negative correlation was also found
      between maximal perfusion during postocclusive hyperaemia in finger and
      fructosamine (r = -0.4, p < 0.01) and between the same parameter in forearm and
      fasting glycaemia (r = -0.62, p < 0.001). Skin perfusion was independent on age
      and duration of diabetes. CONCLUSIONS: Significant differences between diabetic
      patients and healthy controls and a relationship between perfusion parameters and
      compensated diabetes status were described in the current study. Laser Doppler
      fluxmetry is a non-invasive method comfortable for patients and it can be used
      for detection of microangiopathy in diabetology.

PMID- 10953421
TI  - [Effect of normalization of an isolated increase in TSH on the neuropsychological
      profile of patients].
AB  - BACKGROUND: Isolated TSH increase--"subclinical hypothyreosis" (SH) appears to be
      comparatively common. Its incidence among women over sixty has been estimated up
      to 17%. Though SH was assumed to be entirely asymptomatic, recent findings
      revealed various fine subjective and objective symptoms of the disease. METHODS
      AND RESULTS: Twenty otherwise healthy female patients with SH diagnosis were
      examined. Using personality questionnaire MMPI/100 eight different clinical
      scales and two control scales were evaluated, using Wechsler's memory scale WM-R
      5 memory quotients were tested. The group was randomised into a subgroup treated
      for six month with placebo and a subgroup where thyroxin was administrated and
      thyroidal test normalised. Psychological testing repeated before and after the
      treatment, results evaluated using paired t-test. Results indicate that: 1.
      Patients with SH did not differ in personality features, they only had a higher
      tendency to the depressive mood, which could be positively influenced by thyroxin
      (significance at 5% level). 2. Thyroxin treatment brought about improvement of
      some cognitive parameters of the verbal (p < 0.01), visual (p < 0.05), and
      general memory (p < 0.01). 3. Results of psychological and cognitive tests
      correlate better with FT4 than TSH level. CONCLUSIONS: Though SH cannot be
      associated with changes in personality features, TSH normalisation results in
      statistically significant improvement of cognitive function--verbal, visual and
      general memory.

PMID- 10953422
TI  - [Is leptin physiologically important in the regulation of hematopoiesis?].
AB  - Leptin is a protein hormone produced predominantly by adipocytes. Its serum
      concentrations under stabilised energy balance reflect the total body fat
      content. Serum leptin levels represent an important peripheral signal informing
      the hypothalamic satiety center about the body fat stores. Apart from the above
      mentioned functions the possible physiological significance of leptin in the
      regulation of angiogenesis, blood pressure, sexual maturation etc. is suggested.
      The long isoform of leptin receptor belongs to the cytokine receptors group. The
      leptin receptors were identified in some haematopoietic stem cells. Leptin was
      found to stimulate the proliferation of haematopoietic stem cells either alone or
      in combination with some cytokines. Leptin thus seams to represent an additional
      factor that plays a role in the haematopoiesis regulation as it was demonstrated
      by some experimental studies. However, this suggestion needs to be further
      confirmed by clinical studies exploring the changes of serum leptin levels in
      various phases of haematological diseases and during their treatment.

PMID- 10953423
TI  - [Immunoablation and hematopoietic stem cell transplantation in the treatment of
      multiple sclerosis].
AB  - High dose chemotherapy with autologous hematopoietic cell support is a standard
      approach in the management of selected hematological malignancies. Autoimmune
      diseases which do not respond to conventional immunosuppression might benefit
      from high dose immunoablative chemotherapy. The transplantation of hematopoietic
      cells is necessary after the high dose chemotherapy to restore bone marrow
      function. The immune system undergoes a new ontogeny which can result in the
      development of tolerance. Multiple sclerosis (MS) has so far been the most common
      indication for this kind of treatment. Experience with preclinical studies on
      murine experimental allergic encephalomyelitis (EAE), as well as the course of MS
      following bone marrow transplantation for coincidental malignancy in humans
      formed the basis of the first clinical studies involving high dose chemotherapy
      and autologous hematopoietic support. Results of the first studies confirm that
      the method is feasible in patients with MS, and that the effect is very
      promising. Nonetheless, more consistent results vis a vis the therapeutic effect
      should emanate from upcoming studies.

PMID- 10953424
TI  - [Hyperlipoproteinemia, the Apo-E genotype and bone density].
AB  - BACKGROUND: Both atherosclerosis and osteoporosis often appear together,
      especially in the elderly; usually they are regarded as independent entities.
      Only recently epidemiological evidence occurred suggesting possible associations
      between these diseases. Several groups of factors (genetic, hormonal and
      biochemical) have been studied to account for this association. Among the genetic
      factors, apolipoprotein E has been studied most extensively; some results
      indicate that carriers of E4 allele are at increased risk of osteoporosis. A
      possible influence of plasma lipoproteins and of tissue ischaemia on bone
      metabolism has also been studied. AIM OF THE STUDY: To test the hypothesis that
      there is an association between apolipoprotein E, plasma lipid concentrations and
      bone mineral density. METHODS: We examined 18 apolipoprotein E2/2 and E4/4
      homozygotes and 130 postmenopausal women. Bone mineral density and plasma
      triglycerides, total and HDL cholesterol were determined in both groups; in
      apolipoprotein E homozygotes biochemical markers of bone turnover were also
      measured. RESULTS: No significant differences in bone mineral density and bone
      remodelling were found between the E2/2 and E4/4 homozygotes. A negative
      correlation between lumbar spine bone mineral density and cholesterol and
      triglyceride concentrations (r = 0.20-0.39) was observed both in postmenopausal
      women and apolipoprotein E homozygotes. CONCLUSION: We didn't observe any
      association of apolipoprotein E genotype with bone mineral density and
      biochemical markers of bone metabolism. A negative association between plasma
      lipid concentrations and bone mineral density supports the hypothesis of harmful
      effect of hyperlipidaemia on bone metabolism.

PMID- 10953425
TI  - [Comparison of cephalometric parameters in patients with sleep apnea syndrome and
      normal individuals].
AB  - BACKGROUND: Craniofacial abnormalities which predispose to pharyngeal obstruction
      can be detected by cephalometry. The aim of the present study was to compare
      cephalometric findings of the patients with sleep apnoea syndrome (SAS) with
      those of healthy population. METHODS AND RESULTS: The SAS patients (23 females,
      96 males) and normal population (36 females, 50 males) were examined by
      cephalometry. In the group of females with SAS following significant differences
      were observed: elongation of the soft palate (p < 0.001), narrowing pharyngeal
      airway space (p < 0.001), mandibular retrognathism (p < 0.05), micrognathism of
      the mandible (p < 0.001), dorsocaudal rotation of the mandible (p < 0.01),
      increased lower gonion angle (p < 0.001) and the articular angle (p < 0.05),
      increased anterior facial height (p < 0.05), narrowing the depth of bony
      framework of the nasopharynx (p < 0.001), decreased depth of the upper face (p <
      0.01) and decreased length of the cranial base (p < 0.01). In the group of males
      with SAS, following significant differences were observed: elongation of the soft
      palate (p < 0.001), narrowing pharyngeal airway space (p < 0.001), decreased
      depth of the maxilla (p < 0.001), decreased angle of the cranial base (p < 0.01),
      decrease saddle angle (p < 0.01), decreased depth of the upper face (p < 0.01),
      increased lower gonion angle (p < 0.01), increased articular angle (p < 0.001)
      and increased anterior and posterior facial height (p < 0.001). CONCLUSIONS:
      There are important differences in orofacial skeleton and soft tissue of the
      nasopharynx measured by cephalometry in the patients with sleep apnoea compared
      to normal population.

PMID- 10953426
TI  - [The chemiluminescence test in the laboratory evaluation of effects of
      immunostimulatory therapy].
AB  - BACKGROUND: Number of patients treated by general practitioners with various
      immunomodulatory drugs has recently increased. Effects of such medication on the
      immune system were not usually monitored. The aim of our work was to evaluate
      effect of selected immunomodulatory drugs on the phagocytic and metabolic
      activities of the phagocytes. METHODS AND RESULTS: 51 patients (18 males and 33
      females) of the average age 36 years with repeating respiratory, mycotic and
      herpetic infections were investigated. Immunomodulatory treatment included:
      Decaris (Lavamizolum), Isoprinosine (Methisoprinolum), Imudon (Lysatum bacteriale
      mixtum), Biostim (Klebsiella pneumoniae), and Immodin (Leukocyti dialysati
      lyophylysatum). Before and after treatment all patients underwent basic
      immunological examination IgG, IgA, IgM, C3, C4 complement components, PEG, CD3,
      CD4, CD8 and CD19). Phagocytotic activity was estimated by means of FAGO MSHP
      test with HEMA particles and by chemiluminiscence test. Chemiluminiscence was
      measured using ML 3000 Microtiter Plate Luminometer (Dynex), 26 healthy
      individuals of the corresponding age were the controls. Results were
      statistically evaluated by Student's t-test. Significant increase of the cellular
      metabolic activity was found in Decaris and Immodin treated patients (P < 0.001).
      CONCLUSIONS: Chemiluminiscence test, which evaluates the metabolic activity of
      phagocytes, can be used for the accurate laboratory monitoring of the effects of
      some immunomodulatory drugs on the natural immunity of patients.

PMID- 10953427
TI  - [Health care needs and their assessment. Part 1. The role of health needs in the
      development, regulation and evaluation of the health care system].
AB  - The authors draw attention to the fact that higher spending on health care will
      not necessarily translate into better health. They advocate the importance of
      theoretical conceptual work and research in the field of health care and health
      services management. The needs-based approach is recommended as an alternative to
      the current models based on patient-physician interactions. The relationships
      between health needs, demands and health services provided should be further
      explored and their potential role as a basis for health policy in the Czech
      Republic should be addressed.

PMID- 10953428
TI  - [Genetic predisposition for multiple metabolic syndrome. Part 1. Diabetes
      mellitus type 2--incidence and prevalence].
AB  - Multiple metabolic syndrome (MMS) implies a frequent coincidence of four basic
      serious metabolic risk factors for subsequent manifestation of cardiovascular
      disease. The latter include: central type obesity, arterial hypertension,
      dyslipoproteinaemia and diabetes mellitus type II (non-insulin-dependent diabetes
      mellitus--NIDDM). MMS is also described as syndrome X, Reaven's syndrome, insulin
      resistance syndrome, metabolic syndrome or as the "deadly quartet". NIDDM in
      humans is conceived as a syndrome the pathogenesis of which is multifactorial and
      it is not an unequivocal nosological unit. It many epidemiological studies
      reliable evidence was provided that in the aetiology of NIDDM a marked genetic
      influence is involved. Its genetic predisposition is conditioned by the
      interaction of candidate genes and a complex of influences of the external
      environment. Evidence was provided that MMS phenotypes cumulate only in members
      of some families. The mode of genetic transmission of NIDDM remains obscure.

PMID- 10953430
TI  - [Catecholamine plasma levels during the tilt-table test in patients with
      vasovagal syncope].
AB  - BACKGROUND: The head-up tilt test (HUT) makes it possible to diagnose vasovagal
      syncope. The objective of the trial was to follow up changes of catecholamine
      plasma levels during HUT and test their importance in the pathogenesis of
      vasovagal syncope. METHODS AND RESULTS: In 25 patients with syncope of obscure
      etiology during HUT the noradrenalin, adrenalin and dopamine levels were followed
      up. In 125 patients (8 men and 7 women, mean age 34.3 years) HUT was positive.
      The control group was formed by 10 patients with negative HUT (4 men, 6 women,
      mean age 41.1 years). The catecholamine levels were assessed by the method of
      high resolution liquid chromatography during minutes 0, 5 and after completion of
      the test (i.e. during development of the syncope or the 45th minute). On
      comparison by the t-test no statistically significant difference between the
      group with vasovagal syncope and the control group was found. Noradrenalin 0 min:
      186.4 +/- 61.6 pg/ml vs. 190.5 +/- 67.4 pg/ml (n.s.), 5th min. 506.3 +/- 178.9
      pg/ml vs. 566.8 +/- 195.6 pg/ml (n.s.), end of test 457.3 +/- 154.1 pg/ml vs.
      352.3 +/- 169.9 pg/ml (n.s.). Adrenalin 0 min. 54.0 +/- 12.6 pg/ml vs. 54.9 +/-
      13.6 pg/ml (n.s.), 5th min. 114.3 +/- 35.6 pg/ml vs. 128.1 +/- 41.0 pg/ml n.s.,
      end of test 98.2 +/- 40.6 vs. 783 +/- 31.2 pg/ml (n.s.). Dopamine 0 min. 113.9 +/
      36.5 pg/ml vs. 158.4 +/- 67.2 pg/ml (n.s.), 5th min. 318.1 +/- 72.7 vs. 328.5 +/
      119.7 pg/ml (n.s.), end of test 279.4 +/- 93.8 pg/ml vs. 231.7 +/- 98.5 pg/ml
      (n.s.). CONCLUSIONS: Catecholamine plasma levels in patients with vasovagal
      syncope did not differ from the control group. The importance of catecholamines
      in the pathogenesis of vasovagal syncope thus cannot be confirmed.

PMID- 10953431
TI  - [Economic aspects of the treatment of leg ulcers using classical methods and
      modern bandages].
AB  - Costs of conventional and advanced treatments of leg ulcers are compared.
      Conventional treatment consisted in the application of calcaria solution and
      camphor ointment onto the wound and an indifferent pasta onto the surrounding
      skin. The advanced treatments included the use of the novel dressings Granuflex,
      Actisorb and Inadine. The latter treatments consider the sequence of healing
      phases and at the same time shorten the healing period by up one half.
      Comparisons of treatment costs have shown marked benefits of the novel dressings.
      The costs of complete healing of an ulcer with an area of 8 x 8 cm at the healing
      duration of 4 weeks were 503.48 CZK, 432.38 CZK and 329.62 CZK for Granuflex,
      Actisorb and Inadine, respectively. Direct costs of the conventional treatment of
      an ulcer with the same size were 863.28 CZK and the healing period extended to 6
      weeks. The use of the novel dressing is apparently less expensive and affords
      more comfort to the patient.

PMID- 10953429
TI  - [Detection of BCR/ABL, MLL/AF4 and TEL/AML1 hybrid genes and monitoring of
      minimal residual disease in pediatric patients with acute lymphoblastic
      leukemia].
AB  - BACKGROUND: The BCR/ABL and MLL/AF4 fusion genes--resulting from t(9;22)(q34;q11)
      and t(4;11)(q21;q23) translocations, respectively--are considered as a high risk
      prognostic factors in children with acute lymphoblastic leukaemia (ALL). Their
      presence in malignant cells indicates patient for the most intensive
      antileukaemic therapy regardless of the other criteria. In contrast, the most
      common non-random chromosomal aberration in paediatric ALL--translocation
      t(12;21)(q12;q22)--is associated with a favourable prognosis. The examination of
      these rearrangements is important for the stratification of patients to the risk
      groups and also provides the most sensitive and specific tool for minimal
      residual disease (MRD) follow-up. METHODS AND RESULTS: This study comprises 241
      patients with ALL from Czech and Slovak Republics younger than 18 years at
      diagnosis. They were examined for presence of m-RNA of fusion genes BCR/ABL,
      MLL/AF4 and TEL/AML1 by reverse transcriptase-polymerase chain reaction (RT-PCR)
      method. Seven out of 197 (3.6%) carried MLL/AF4 fusion gene, but among infants it
      was 56% (5 out of 9). BCR/ABL positivity was found in 2.5% (7 out of 240) and
      TEL/AML1 in 21.7% (41 out of 189) cases. Event free survival (EFS) curves
      demonstrate the clinical impact of these hybrid genes on patients' prognosis.
      Moreover, we present the possibility of the monitoring of MRD levels in follow-up
      samples of these patients. CONCLUSIONS: All particular rearrangements were found
      only in a cohort of patients with B-precursor ALL (or hybrid leukaemia), which
      constitutes 85% of our group. Presence of BCR/ABL or MLL/AF4 fusion gene is
      associated with poor prognosis and is indispensable condition for correct
      stratification of patients to the risk groups according to treatment protocols.
      Hybrid gene TEL/AML1 defines subgroup of children with better prognosis and due
      to its high frequency provides us with a very useful tool for MRD detection.

PMID- 10953432
TI  - [Dr. Vlasta Kalalova-Di Lottiova--the Czech Schweitzer].

PMID- 10953433
TI  - [The year 2000--the 49th anniversary of the journal, Czech and Slovak Pharmacy].

PMID- 10953434
TI  - [Xenobiochemistry at the turn of the millenium].

PMID- 10953435
TI  - [Nomenclature of drug forms--overview of development and the present state].
AB  - If the names used for dosage forms in pharmacopoeias and professional literature
      are examined, changes are found which are not always connected with extended
      knowledge about preparations, or the development of new variants of the dosage
      form. The same finding holds true for their classification into systematic
      groups. The problem has become particularly topical within the framework of
      international co-operation. The objective of the present paper is to inform about
      the steps aiming at standardisation of their nomenclature at least in Europe.

PMID- 10953436
TI  - [Correct pharmacotherapy].
AB  - The developments in the pharmaceutical profession have been changing the
      importance and share of the individual professional activities in it. The work
      with the pieces of information and with the patient, and advisory and consulting
      activities, which take place in monitoring pharmacotherapy, have become dominant.
      In this connection the paper elucidates the individual attributes of the concept
      of good drug therapy, the concept of good prescribing, various forms of the
      attitudes and behaviour of the patient in relationship to therapy, and the
      problems of medication errors.

PMID- 10953437
TI  - [The human hepatocyte. II. Cryopreservation].
AB  - Human hepatocytes (HH) are an optimal in vitro model for the study of xenobiotics
      metabolism and toxicity. However, there is still a problem of HH availability. A
      promising possibility for the storage of HH for later utilization is
      cryopreservation. Procedures and conditions used for cryopreservation of human
      hepatocytes and hepatocytes of other species are presented in the present paper.
      Compared are some biochemical parameters characterizing viability and
      functionality of fresh and thawed HH.

PMID- 10953438
TI  - [Occurrence and use of anthracenones].
AB  - The present paper aims to inform the pharmaceutical public about anthracenons and
      their natural producers. The first available mention dates from 1888 and the
      present authors also describe their synthesis and use in clinical practice.

PMID- 10953439
TI  - [Sterols in Lilium candidum L].
AB  - From the butanolic extract of petals of Lilium candidum L., beta-sitosterol and
      beta-sitosterol glucoside were isolated. The isolated compounds were identified
      by spectroscopic means and by comparison with literature data; beta-sitosterol
      glucoside was isolated in genus Lilium L. for the first time.

PMID- 10953440
TI  - [Antibacterial and antineoplastic activity of 2,4-disubstituted 6H-5,1,3
      benzothiadiazocines].
AB  - Nine 2,4-disubstituted 6H-5,1,3-benzothiadiazocines have been tested for
      antibacterial and cytotoxic efficacy. None of the tested compounds showed any
      significant antibacterial activity in comparison with ampicillin. The most
      cytotoxic effect was manifested by those derivatives which have morpholine or
      phenyl in position 2 and benzimidazole, imidazole or 1,2,4-triazole in position
      4. The highest concentrations of derivatives I, VII, IX induced an acute
      cytotoxic effect which was manifested by cell lysis after 24 h of culturing.
      Derivative VII, concentration 30.5 mumol/L, and derivative IX, concentration 13.3
      mumol/L, exhibited a delayed cytotoxic effect on L1210 cells. While during the
      first 24 and 48 h a certain part of cell population proliferated, during further
      24 h a total inhibition of cell division was found. The cytotoxic concentration
      of derivative IX induced damage to the integrity of the cytoplasmic membrane.
      Benzothiadiazocines I, VII and IX induced a two-phase unbalanced growth. Based on
      these results, benzothiodiazocines I, VII and IX could be considered new
      potential anticancer drugs which are appropriate for further research.

PMID- 10953442
TI  - [Pharmacodynamic parameters of gentamicin and its effect on the surface
      hydrophobicity of Acinetobacter baumannii].
AB  - The postantibiotic effect (PAE) and postantibiotic effect of subinhibitory
      concentration (PA SME) of gentamicin as well as influence of these
      pharmacodynamic parameters on surface hydrophobicity of three Acinetobacter
      baumannii strains were studied in vitro. Suppression of bacterial growth (PAE)
      after a short time exposure of bacteria to gentamicin (30 min) at suprainhibitory
      concentration 2x MIC was in the range of 0.6 h to 3.4 h. Longer PAE was observed
      after treatment of bacteria with gentamicin at 4x MIC (1.5 h-5.1 h). Supra
      subinhibitory concentrations of gentamicin (2x or 4x MIC + 0.2x MIC) caused still
      more effective delay of bacterial regrowth (PA SME) in comparison with
      suprainhibitory concentrations for one strain (9.1 h and 9.6 h) and in the case
      of further two strains they were so efficient that regrowth of bacteria was not
      observed for 24 h. Surface hydrophobicity of the gentamicin treated strains
      evaluated by adherence of bacteria to xylene ranged from 90.0% to 99.7% of the
      control values (without antibiotic).

PMID- 10953441
TI  - [The effect of panpal prophylaxis on acetylcholinesterase activity in the blood,
      diaphragm and various parts of the brain in rats during treated and untreated
      poisoning with the organophosphorus insecticide phosdrine]].
AB  - In experiments on male rats the paper investigated the effect of pharmacological
      prophylaxis with Panpal (pyridostigmine in combination with benactyzine and
      trihexyphenidyl) on the activity of acetylcholinesterase in the whole blood,
      diaphragm, and selected parts of the brain (frontal cortex, pontomedular region,
      hippocampus, cerebellum) at hour 1 and 3 of untreated and treated (oxime HI-6
      with atropine) intoxication with the organophosphorous insecticide phosdrine.
      Whereas in the CNS Panpal did not produce statistically significant changes in
      the activity of acetylcholinesterase in the course of untreated and treated
      phosdrine intoxication, in the blood and diaphragm Panpal markedly intensified
      phosdrine-induced inhibition of the acetylcholinesterase activity and, in
      addition, decreased the reactivating effect of the oxime HI-6. The data give
      evidence of the importance of the combination of the prophylactically used
      reversible acetylcholinesterase inhibitor pyridostigmine with anticholinergics,
      which could eliminate the consequences of a pyridostigmine-induced decrease in
      the activity of the enzyme in the periphery.

PMID- 10953443
TI  - [The effect of aryloxyaminopropanol substances on the photosynthetic activity of
      chloroplasts in Spinacia oleracea L].
AB  - The effect of 18 compounds of the aryloxyaminopropanol type--potential beta
      adrenolytics (differing each from other by modifications in the hydrophilic and
      lipophilic part of the molecule) on the inhibition of oxygen evolution rate in
      spinach chloroplasts has been investigated. The compounds with n-octyloxymethyl
      and n-nonyloxymethyl group in position 3 of aromatic ring were found to exhibit
      the highest inhibitory activity (IC50 = 67, resp. 120 mumol dm-3). The compounds
      containing a heterocycle or the dimethylamino group in the hydrophilic part of
      the molecule and with propoxymethyl group on the aromatic ring were not active.
      Using EPR spectroscopy it was found that the studied compounds interact with
      Z+/D+ intermediates, i.e. tyrosine radicals TyrZ and TyrD situated in D1 and D2
      proteins on the donor side of photosystem 2. Higher concentrations of the studied
      inhibitors cause release of Mn2+ ions from the oxygen evolving complex which is
      situated in photosystem 2. The interaction of the tested compounds with
      chlorophyll occurring in the photosynthetic centres has been confirmed by
      fluorescence measurements as well.

PMID- 10953444
TI  - [Mucoadhesive oral tablets--a modern dosage form with controlled drug release].
AB  - The review paper summarizes the principal pharmaceutical and medical information
      about the hitherto achieved results in the development of bioadhesive dosage form
      concentrating on mucoadhesive oral tablets. The site of administration of the
      tablets is the facial pocket. Due to specific properties of the mucous layer on
      the buccal mucosa and mucoadhesive polymers from which the tablets are
      manufactured, tablets adhere to the mucosa. The adhesion may take a certain
      period of time and during the whole period the active ingredient is gradually
      released. Absorption of the drug through the mucous membrane of the oral cavity
      has a number of advantages, in particular with respect to the stability of the
      drug. Various types of mucoadhesive tablets are being developed. The system
      releasing the drug only in one direction, i.e. direct to the mucosa, seems to be
      very advantageous. In the evaluation of mucoadhesive tablets, two parameters are
      of particular importance, the bioadhesive force and the rate of drug release.
      Oral mucoadhesive tablets can be employed in the treatment of both systemic and
      local diseases.

PMID- 10953446
TI  - [Chemical structure of quinolones and their antibacterial activity. II. 4
      quinolones: their occurrence in nature and biological properties].
AB  - The review paper deals with the natural occurrence, biological properties, and
      uses of 4-quinolones concentrating on 3-substituted-4-quinolones and their
      antimicrobial activity.

PMID- 10953445
TI  - [Effective and safe pharmacotherapy of acne vulgaris and treatment of sun-damaged
      skin].
AB  - An inevitable condition for the pharmacist is a basic knowledge of dermatological
      changes which are prominent in acne and solar impairment of the skin to be able
      to recommend in a qualified manner an effective and safe treatment to the
      patient. However, sufferers of the more serious forms of acne should always be
      referred to their general practitioner, or preferentially a dermatologist. Acne
      vulgaris is an androgen-induced disorder, but three major mechanisms for the
      development of the disease have been identified: hypertrophy of the sebaceous
      gland, hyperkatosis of the follicular epithelium, and proliferation of microbial
      flora, particularly Propionibacterium acnes. The basis of all lesions is the
      microcomedone which is developed into the ripe comedone. Inflammatory lesions are
      thought to be due to proliferation of P. acnes. In the selfmedication of common
      acne, benzoyl peroxide, which in a 5-10% lotion exerts antimicrobial and
      keratolytic properties, proved to be useful. Patients appreciate a lot its
      instant effect which is visible after just one day of treatment. Salicylic acid
      is another effective drug, which, when used on the long-term basis, has
      comedolytic properties; it reduces the number of microcomedones and counteracts
      plugging of the follicles. In addition, in healthy young women who take oral
      contraception, a triphasic combined oral preparations of contraceptives with
      newer progestins, notably with norgestimmate, which is practically free of
      androgenic effects, are recommended with advantage for the treatment of moderate
      acne vulgaris without any adverse effects. Solar impairment of the skin, the so
      called solar ageing, is clinically indistinguishable from biological ageing.
      Changes connected with solar impairment appear mostly in the dermis, where solar
      elastosis develops, the skin gets drier and wrinkle formation appears. For the
      treatment, hydroxy acids are recommended, namely salicylic acid, which is very
      effective, because in combination with a suitable vehicle it produces
      desquamation or exfoliation. Desquamation is beneficial as it gives a youthful
      appearance to the skin.

PMID- 10953447
TI  - [Apigenin-7-methylglucuronide from Cynara cardunculus L].
AB  - From an ethanolic extract of the flower buds of Cynara cardunculus L.
      (Asteraceae), apigenin-7-methylglucuronide and chlorogenic acid were isolated.
      The isolated compounds were identified by spectroscopic means, by comparison with
      authentic samples and literature data.

PMID- 10953448
TI  - [Effect of linoleic acid on the production of secondary metabolites].
AB  - The paper examines the effect of linoleic acid in various concentrations on the
      production of flavonoids in an Ononis arvensis culture in vitro and the
      production of anthracene derivatives in a Rheum palmatum culture in vitro. The
      content of the metabolites under study after elicitation with linoleic acid,
      which is the precursor of jasminic acid intervening into the course of
      elicitation, was examined after 12; 24; 48 and 168 hours. The maximal increase in
      the content of flavonoids (118%) was found after the application of linoleic acid
      in a concentration of 2 mg/ml after 48 hrs. In concentrations of 0.01; 0.20, and
      1 mg/ml after 48 hours of application of the elicitor, the highest increase in
      the content of flavonoids was observed after 24 hrs in a concentration of 2.0
      mg/ml. In the elicitation of the Rheum palmatum culture, the highest response
      (100%) in the production of anthracene derivatives was observed in linoleic acid
      in a concentration of 1 mg/ml.

PMID- 10953449
TI  - [HPLC analysis of nonsteroidal antirheumatic agents in biological materials. IV.
      Acetic acid derivatives].
AB  - The present paper surveys the published HPLC methods estimating derivatives of
      acetic acid in biological materials and an HPLC method for estimation of
      indomethacine in the samples of whole blood. The elaborated chromatographic
      conditions and process of isolation were applied also to the analysis of
      tropesine and both drugs were determined simultaneously. The blood samples were
      adjusted by liquid-liquid extraction and indomethacine (and tropesine) was
      analysed on the reverse phase Separon SGX C-18 with the mobile phase methanol
      water (pH 3.2) and detected at 254 nm. The method was used in a pharmacokinetic
      study of indomethacine on rabbits.

PMID- 10953450
TI  - [Determination of xanthinol nicotinate in drug preparations using capillary
      isotachophoresis].
AB  - Cationic capillary isotachophoresis (ITP) with coductimetric detection has been
      used for separating and determination of xanthinol in two commercial mass
      produced preparations. The optimized ITP electrolyte system consisted of 5 mM
      potassium picolinate + 5 mM picolinic acid (pH 5.21) as the leading electrolyte
      and 10 mM formic acid as the terminating electrolyte. The driving and detection
      currents were 50 microA (for 380 s) and 10 microA, respectively. The analysis
      took about 8 min. According to the validation procedure based on the reference UV
      spectrophotometric method, the ITP method gave practically the same results.

PMID- 10953451
TI  - [Labeling products of photochemical degradation of insulin with technetium
      (99mTc)].
AB  - Irradiation with UV light at a wavelength of 250 nm allows to convert disulphidic
      groups in the structure of insulin to free SH groups with high affinity to direct
      labelling with 99mTc. The amount of terminal SH groups depends on irradiation
      time. HPLC analysis revealed that while 34% of the original amount of insulin was
      present after 15 minutes of irradiation (approx. intensity of 500 microW.cm2),
      the amounts were 25%, 10%, and 2% after 30; 60, and 120 minutes, respectively.
      These results correlate with the amount of SH groups released by photoactivation
      measured using Ellman's reagent. The product of the degraded porcine insulin was
      labelled with 99mTc using the redox polymer RP G25 IDA under the following
      conditions: pH 6.8-7.9, labelling time 15 minutes, room temperature.
      Radiochemical purify of the labelled product was higher than 96%. Insulin and
      products of its degradation were evaluated by means of size exclusion
      chromatography (SEC). The biodistribution of the labelled substances in
      laboratory animals showed activity mostly in the kidneys and liver. No specific
      biodistribution of the labelled products was observed in rats with experimentally
      induced diabetes.

PMID- 10953452
TI  - [Drug forms as the subject of a dissertation in the historical past of Charles
      University].
AB  - The "galenical" dissertation which was presented for disputation by Georgius
      Horcicka at Charles University in 1841 is discussed as far as its content is
      concerned. The dissertation studies a great number of pharmaceutical dosage
      forms, many of which are already obsolete, but a certain number of which are
      still in use in the present time. It is probably one of the first dissertations
      treating of the given subject.

PMID- 10953453
TI  - [Coffea arabica--production, botanical classification, new components and active
      agents and their pharmacological effects].
AB  - The present paper surveys the latest knowledge about coffee grains (Coffea
      arabica) as an important part of our everyday life. It lists the botanical
      classification of its principal species, such as Coffea arabica, Coffea robusta,
      and Coffea liberica, the most important improved cultivars of production species
      in the world. The review paper also discusses the economic aspect, lists the most
      important regions of production, the optimal and farming technological
      conditions. It points out the occurrence of the individual constituents which
      have been hitherto isolated, characterized, and chemically defined with some of
      their physiological effects on the human organism, e.g., the substances of the
      diterpene type such as kafestol and kahweol and their structure.

PMID- 10953454
TI  - [Antitubercular derivatives of quinazoline].
AB  - The study is a review paper about the development of antituberculous substances
      in the group of quinazoline derivatives. Most antituberculous compounds under
      study contain the pertinent pharmacophores in the functional groups and their
      antituberculous activity cannot be considered to be specific for quinazolines.
      Nevertheless, several groups of antituberculously effective quinazoline
      derivatives were found which do not contain the known pharmacophores of
      antituberculous activity. The substances are, on the rule, of medium activity,
      but the activity of some of them, evaluated in vitro, approaches that of commonly
      used antituberculous agents. They can thus initiate new research in this
      direction. The present paper is already the 12th communication in a series of
      review papers about substances with antituberculous activity.

PMID- 10953455
TI  - [Coenzyme Q10--its importance, properties and use in nutrition and cosmetics].
AB  - Coenzyme Q10, or ubiquinone, is a nutrient--a vitamin-like substance which plays
      a crucial role in the generation of cellular energy an in free radical scavenging
      in the human body. After the age of 35 to 40, the organism begins to lose its
      ability to synthesize Co Q10 from food and its deficiency develops. Ageing, poor
      eating habits, stress and infection--they all affect our ability to provide
      adequate amounts of Co Q10. Therefore Co Q10 supplementation may be very helpful
      for the organism. The present summarizing study reports the history of the
      discovery and research, properties, biochemical effects, dosage of Co Q10
      deficiency in the human body. A possible use of Co Q10 as a dietary supplement
      and an ingredient for topical cosmetic products is described.

PMID- 10953456
TI  - [Rheologic properties of viscoelastic materials--identification of models and
      estimation of parameters].
AB  - The methodology of description and quantification of mechanical properties of
      visco-elastic materials is particularly important for drug production as well as
      for pharmaceutical applications. Of similar importance is this methodology for
      biomechanics and other biological disciplines, as many biological materials
      belong to the category of visco-elastic bodies. Methods derived from the theory
      of elastic bodies or hydrodynamics are not adequate for the quantification of
      mechanical properties of these materials. Application of more general rheological
      methods is necessary in these cases. In rheology, the so-called creep curves are
      most frequently used as a source of information on the mechanical behavior of
      visco-elastic materials. Further, for more exact analysis, rheological models are
      often derived from the creep curves. Classical methods of identification and
      parameter estimation of rheological models are not sufficiently general and do
      not derive all information involved in creep curves. A significant contribution
      is the application of the general theory of systems, theory of system
      identification, and mathematical methodology of Laplace transformation to this
      field. Practical application of these methods is often relatively simple. The
      paper presents the necessary theoretical background and a practical guide for
      utilization of this methodology.

PMID- 10953457
TI  - [Mn and Zn content in the plant drug from Folium betulae grown in various
      locations].
AB  - In the plant drug collected at different localities in Slovakia and Bohemia in
      the same vegetation period of one year, the content of Mn and Zn were determined.
      The AAS method was employed after mineralization of the drug by the dry method
      (without mineralizing additives) and subsequent dissolution of the ash in a HCl
      solution. The content of both metals in the samples substantially differed (Mn:
      24.7-2095.5 mg/kg, Zn: 46.5-362.0 mg/kg of the dried drug). The content of the
      ash, which was within the limits of the standard, excludes excessive pollution by
      dust fall-out. The birch tree most probably absorbs and cumulates Mn and Zn from
      the soil.

PMID- 10953458
TI  - [The effect of ascorbic acid on the antibacterial activity of selected
      antibiotics and synthetic chemotherapeutic agents in in vitro conditions].
AB  - The study was aimed to determine the ability of selected antibiotics and
      synthetic chemotherapeutic agents to interact with ascorbic acid by means of
      spectrophotometric measurements and the evaluation of the effect of the presence
      of ascorbic acid on antimicrobial activity of the substances in which the
      interaction was detected. Out of 13 chemotherapeutical agents tested, ofloxacine,
      N-succinimidylofloxacine, fleroxacine, tetracycline, 6-thiatetracycline, and
      doxycycline reacted with ascorbic acid with the development of the superoxide
      radical (O2.-). Heatley's method revealed that in the presence of ascorbic acid
      the antibacterial effect of substances was decreased by 9.6 to 40.7% and 10.1 to
      45.1% in Staphylococcus aureus and Escherichia coli, respectively. The kinetics
      of the process of the survival of cells within 24 hours demonstrated that a
      combination of ofloxacine as well as tetracycline with ascorbic acid produced a
      statistically significant increase in log10 of CFU/ml in S. aureus as well as E.
      coli.

PMID- 10953459
TI  - [Detection of secretion of beta-galactosidase by plant cells].
AB  - A simple, sensitive and reproducible method of detection of extracellular beta
      galactosidase was worked out. beta-Galactosidase secreted by the callus culture,
      or the roots of sprouting plants, hydrolyzes the substrate (6-bromo-2-naphthyl
      beta-D-galactopyranoside) to produce beta-D-galactose and 6-bromo-2-naphthol,
      which after simultaneous azocoupling with hexazotized p-rosaniline, or basic
      fuchsine, produce a reddish brown compound, nearly insoluble in water (a
      diazonium salt). The colouring under the callus culture and around it, as well as
      the colouring of the roots of the sprouting plants, is a manifestation of the
      activity of extracellular beta-galactosidase by the objects under study. The
      intensity of the colouring is a measure of their enzymatic activity. The share of
      intracellularly localized enzyme represents the majority and the share of
      extracellular beta-galactosidase the minority.

PMID- 10953460
TI  - [Effect of macromolecular substances on pharmaceutical availability of a
      potential local anesthetic].
AB  - Within the framework of the study of the derivatives of phenylcarbamic acid with
      a local anaesthetic effect, one of them, a potential medicinal agent with the
      working name of XX B, chemically N-[2-(3-heptyloxyphenylcarbamoyloxy)-ethyl]
      dimethylammoniumchl oride, was investigated. Linking up with the previous
      studies, the paper investigated the effects of two auxiliary substances-
      cellulose derivatives (hydroxyethylcellulose, methylcellulose)--and their
      concentration on the pharmaceutical availability of the potential drug XX B from
      the dosage form. At the same time the effect of the employed concentration of the
      macromolecular substances on the viscosity of the dosage form was examined. The
      study revealed that with the growing concentration of cellulose derivatives the
      viscosity of the prepared dosage forms was increased, and the release of the
      active ingredient was decelerated. Both auxiliary substances influenced the
      pharmaceutical availability of the potential drug XX B in an approximately
      identical manner, and thus both could be employed for the same purpose.

PMID- 10953461
TI  - [Effect of magnesium stearate on internal failure of Avicel PH 101 tablets].
AB  - The effect of the incorporation of different concentrations of magnesium stearate
      (0, 0.4, 0.8, and 1.2%) on the texture of the tablets from Avicel PH 101 was
      investigated by means of the examination of their tensile strength and the values
      of Weibull's modules. It has been found that with an increasing forming pressure
      the decrease in the tensile strength of tablets is increased. No significant
      difference in the decrease in tensile strength was found between stearate
      concentrations of 0.4 and 0.8%. The incorporation of magnesium stearate into the
      tableting material, by decreasing the friction between the particles, minimizes
      possible incidence of more marked disorders in the texture of tablets.

PMID- 10953462
TI  - [Effect of potential beta-adrenolytics on markers of enzyme activity in
      subcellular fractions of the cardiac muscle].
AB  - The paper investigates the effect of two potential beta-adrenolytical agents, 1
      [4-(3-isopropylamino-2-hydroxypropoxy)-3-(propoxymethyl)phenyl]etan on (FA33) and
      1-[4-(3-isopropylamino-2-hydroxypropoxy)-3-(propoxymethyl)phenyl]prop anan-1-on
      (FP33), in the form of salts with fumaric acid on the enzymatic activities of the
      markers of subcellular fractions of the rabbit cardiac muscle (in vitro). In the
      mitochondria, both substances inhibit the specific activity of cytochromoxidase
      (FA33 by 37.14% and FP33 by 35.88%). In the sarcolemma, substance FA33 inhibits
      the specific activity of Na(+)-K(+)-ATPase by 23.02%, while substance FP33
      possesses an activating effect increased by 23.24%. In the sarcoplasmatic
      reticule both substances inhibit the specific activity of Ca(2+)-Mg(2+)-ATPase
      (FA33 by 14.96% and FP33 by 8.79%). The different effects of substances FA33 and
      FP33 on the activities of the markers of the subcellular fractions of the cardiac
      muscle can be connected with different inotropism of both substances.

PMID- 10953463
TI  - [Drugs as relief aid or as waste disposal?].

PMID- 10953464
TI  - [Interactions between herbal medicines and drugs].
AB  - At present the use of medicaments of plant origin is on the increase. It is
      therefore necessary to take into consideration that there exist known as well as
      potential interactions between the medicament of the medicinal plant. The
      problematic plants include Echinacea, Allium cepa, Gingko biloba, Panax ginseng,
      as well as Hypericum perforatum, Valeriana officinalis, or Glycyrrhiza glabra.
      Its use should be limited, or completely excluded in the cases of simultaneous
      therapy with, e.g., warfarin, hepatotoxically acting medicaments, MAOI
      inhibitors, phenelzin sulphate, or phenytoin, as they may decrease of completely
      eliminate the therapeutic effect of the administered drugs, or they may cause a
      toxic damage to the organism.

PMID- 10953465
TI  - [Curcumin as a potential antioxidant].
AB  - Curcuma vera is one of the medicinal plants of traditional Chinese medicine. The
      plant is the natural source of one of natural antioxidative agents--curcumin. The
      present paper summarizes information about the properties of curcumin and
      presents the characteristics of Curcuma vera, its producer.

PMID- 10953466
TI  - [Role of amine oxidase in the biosynthesis of alkaloids].
AB  - The review paper deals with the contemporary theoretical knowledge about the role
      of Cu-aminooxidase in the biosynthesis of alkaloids in plants. In the
      biosynthesis of tropane and piperidine alkaloids, aminooxidase participates in
      the conversion of amines into aldehydes which are the first important
      intermediates in the biosynthesis of these alkaloids. Norkoklaurine, the
      precursor of benzylisoquinoline alkaloids, is formed by condensation of dopamine
      and tyral. In the biosynthesis of benzylisoquinoline alkaloids of protoberberine
      and berberine type, tyral, the aldehyde condensation unit, is produced by the
      action of aminooxidase. In morphinan alkaloids, the catalytic role of
      aminooxidase in the formation of tyral have not been demonstrated yet. The paper
      pays special attention to the mechanism of the aminooxidase-catalyzed reaction,
      the structure of the active site of the enzyme, and the molecular-biological
      properties of Cu-aminooxidases.

PMID- 10953467
TI  - [Effects of a (fluorophenyl) piperazine derivative (substance IIIv) on
      cardiovascular function].
AB  - The present paper links up with the study of principal pharmacological effects of
      newly synthesized aryloxyaminopropanols substituted with 1,4-piperazine
      derivatives in the hydrophilic moiety of the molecule. The substance with the
      working name IIIv showing the highest beta-adrenolytical and vasodilating effect
      underwent further pharmacological evaluations with the aim of contributing to the
      elucidation of the mechanism of its action. After 7-day administration of the
      substance in two doses (5 and 50 mg.kg-1), the changes in the reactibility of
      arterial preparations were investigated on three models of the contraction of the
      isolated rat aorta (KCl, noradrenaline, and PGF2 alpha) from both qualitative and
      quantitative views. The results were also supplemented with organometric studies
      of the effect of the substance in rats.

PMID- 10953468
TI  - [Fractal dimensions of powders used as pharmaceutical dusting powders].
AB  - The paper examines the use of the fractal dimension for the expression of the
      shape of random aggregates of primary particles of four powders for
      pharmaceutical dusting powders. The values within a range from 1.14 to 1.24 are
      compared with the results of the equilibrium gravitational classification within
      a range from 15 to 45 microns. Vacillation of the fractal dimension is influenced
      by the values of the specific surface determined from the parameters of the RRS
      distribution of elutriation. The fractal dimension extends the morphological
      characteristics of powders. For the needs of pharmaceutical technology it is,
      however, necessary to specify better the conditions of its determination, above
      all in the selection of a suitable range of the dimension of evaluation ("walk")
      with regard to the largest dimension of the aggregates of powders.

PMID- 10953469
TI  - [In vitro and in vivo physicochemical study of depot formation of cinchocaine in
      an atelocollagen matrix].
AB  - The paper presents an introductory physicochemical study dealing with the
      preparation of atelocollagen felt saturated with local anesthetics, with the
      modelling of the release of the anesthetic from the collagen matrix in vitro, and
      with the checking of the corresponding analytical procedures (dc-polarography and
      UV-VIS spectrophotometry) for the determination of cinchocaine. The study is
      supplemented with experiments in vivo that confirm the usability of the new
      material for the depot formation of local anesthetics.

PMID- 10953470
TI  - [Analysis of cardioplegic solutions using capillary isotachophoresis].
AB  - The method of capillary isotachophoresis was employed to analyze a cardioplegic
      solution containing sodium, potassium, calcium, and magnesium ions and procainium
      chloride. The results of ITP measurements were compared with the results obtained
      by means of the standard pharmacopoeial methods and in the case of alkalis also
      with the results of AAS. Precision, correctness, linearity, robustness, and
      selectivity of the ITP were evaluated.

PMID- 10953471
TI  - [Evaluation of the quality of mexiletine hydrochloride using capillary
      electrophoreses].
AB  - Mexiletine hydrochloride and its potential impurity xylenol were determined by
      micellar electrokinetic chromatography in a 25 cm long capillary. The effect of
      parameters--temperature, electric field, concentration of analyzed compounds,
      type and composition of background electrolyte--on the separation of analytes and
      precision of analysis was studied. The advantage of the elaborated method is a
      very short time of analysis (2.3 min) at the sufficient level of precision and
      reliability of results.

PMID- 10953472
TI  - [Oxidative determination of hydroxyamphetamine in drops using flow injection
      analysis].
AB  - A flow injection-spectrophotometric determination at 540 nm of hydroxyamphetamine
      is reported. The procedure is based on a coloured reaction with 2-hydrazono-3
      methylbenzothiazole (MBTH) and ceric ammonium nitrate (CeIV) as the oxidation
      reagent. Under optimised conditions, the determination of hydroxyamphetamine is
      achieved in a range of 0.01-0.2 mmol.l-1 with a relative standard deviation of
      0.78% for 0.05 mmol.l-1 (n = 10) and a sample throughput of 75.h-1. The method
      was used for the determination of medicinal drug in the mass-produced dosage form
      of Czech origin: Pedrolon drops, Galena a.c.

PMID- 10953473
TI  - [Anti-inflammatory activity of copper and zinc p-cresol dihydrate].
AB  - Using rat paw dextran-induced and carrageenan-induced edemas, the antiedematous
      activities of dihydrate of diaquatetrakis(p-cresotato)dicopper(II) complex (CupC)
      and diaquabis(p-cresotato)zinc(II) complex (ZnpC) were assayed
      plethysmometrically. Dihydrate of diaquabis(salicylato)copper(II) complex (CuS)
      and diaquabis(salicylato)zinc(II) complex (ZnS) were used as standards of
      comparison. All compounds were applied i.p. in a single dose of 50 mumol/kg body
      weight (calculated for the RCOO-fragment) 30 min before injecting the irritant.
      The antidextran/anticarrageenan activities of the species (expressed as a mean
      edema reduction) were found: CupC 46/74%--ZnpC 50/26%--CuS 71/52%--ZnS 63/10%.
      The relationships between the coordination-chemical properties and the biological
      effects of the corresponding complexes are discussed.

PMID- 10953474
TI  - [Results from the Registry of Complications in Users of Hormonal Contraception in
      1998].
AB  - OBJECTIVE: To collect data on the use of hormonal contraception in the Czech
      Republic in 1998. SETTING: Department of Gynaecology and Obstetrics, Charles
      University School of Medicine and General University Hospital Prague. METHODS: A
      total of 2,134 questionnaires were sent to Czech gynaecologists in spring 1999. A
      total of 418 answers were processed. RESULTS: The estimated number of users
      presenting in gynaecologist's offices participating in our project was 237,099
      women. The most often prescribed contraceptives were monophasic products (54.38%)
      containing 30-35 micrograms of ethinyl-estradiol (55.21%) with new progestins
      (53.8%) (norgestimate, gestoden, desogestrel). Regular follow-up of hormonal
      contraceptive users included the following examinations/tests: blood count in
      8.5% offices, ultrasound examination in 8.0% offices, lipid spectrum in 49.8%
      offices, blood pressure in 74% offices, colposcopy in 97.6% offices, oncological
      cytology in 98.4% offices and liver tests in 77.1% gynecologist's offices. Only
      10.85% of the gynaecologists did not perform lipid tests, almost 20%
      gynaecologists measured blood pressure only selectively in some users. 80 cases
      of cardiovascular disease were diagnosed, a figure consistent with an 0.0325%
      incidence of users. The most frequent complication was deep venous thrombosis (58
      cases). The subgroup of women experiencing a cardiovascular event was not
      characterized by older age, higher body weight, more frequent smoking, or use of
      products with a higher oestrogen contents. CONCLUSION: There were major
      differences among gynaecologists in the follow-up of hormonal contraception
      users. The pattern of the products used varied markedly by regions. The number of
      diagnosed cardiovascular diseases was very low. Users with a previous a
      cardiovascular event were only exceptionally carriers of a risk factor.

PMID- 10953475
TI  - [Prediction of the effect of a triphasic contraceptive agent with norgestimate on
      acne].
AB  - OBJECTIVE: Prediction of complexion changes in users of triphasic oral
      contraceptive containing norgestimate. DESIGN: Analysis of data from a
      prospective multicentre open study. SETTING: Department of Obstetrics and
      Gynaecology, Charles University, Prague. METHODS: Acne severity was evaluated in
      users of a triphasic norgestimate-containing contraceptive within a six month
      period. Based on subjective evaluation of acne, three subgroups of patients were
      selected: A) users where acne improved or disappeared; B) users in whom acne
      deteriorated, C) users who newly developed acne. Differences between group A and
      the other groups were established in the proportion or distribution of parameters
      related to the etiology of acne: age, weight, weight changes during the study,
      presence of hirsutism, presence of a regular menstrual cycle prior to the start
      of hormonal contraception use, and smoking. RESULTS: The effect of the pill use
      on acne was assessed in a total of 3,990 women. Out of 1,201 women with acne
      before the start of the study, improvement or disappearance of acne during the
      study was reported by 940 users (subgroup A) (78.27%). In 221 women (18.40%), the
      extent of acne remained unaltered whereas it increased (subgroup B) in only 30
      women (2.50%). Acne newly developed during the study in 49 women (subgroup C),
      i.e., in 1.2% of the whole group. Users showing deterioration of acne (subgroup
      B) were found to have hirsutism less frequently. The subgroup even showed a
      decrease in mean weight during the study. Users with newly developed acne were-
      compared with subgroup A--significantly older, had a lower weight at the start of
      the study, and showed a higher frequency of regular menstrual cycles prior to
      starting hormonal contraception. The differences in the incidence of clinical
      parameters in the subgroups reached only borderline statistical significance and,
      hence, are not relevant. CONCLUSION: An extensive multicentric study confirmed
      the beneficial effect of a triphasic norgestimate-containing contraceptive on
      complexion. The presence of clinical parameters related to the etiology of acne
      does not allow to predict the individual response of the skin to hormonal
      therapy.

PMID- 10953476
TI  - [Reproductive health in women in the Czech Republic 1993-1997. I. Study
      methodology and characteristics of the sample groups].
AB  - AIM OF THE STUDY: To identify changes in reproductive health status as a
      consequence of changes in the system of health care and social affairs. THE AIM
      OF THIS PART OF STUDY: To prepare the methodology of data collection and to
      identify changes of demographic characteristics. TYPE OF THE STUDY: Retrospective
      comparative epidemiological study. INSTITUTION: Institute for the Care of Mother
      and Child, Praha 4-Podoli. METHODS: Two nation-wide surveys on reproductive
      health of representative three-stage cluster samples in 1993 and 1997. After
      selection of residential sites from all districts the households were selected
      for interview. One hundred and fifty trained interviewers asked selected women of
      reproductive age (4,497 in 1993 and 1,735 in 1997) questions according to a
      special questionnaire. The basic demographic characteristics of the two samples
      were compared with the 1991 Census data. The 1993 Czech Republic Reproductive
      Health Survey was funded by the United States Agency for international
      Development via a WHO agreement; the 1997 Survey was funded by the Czech
      Statistical Office and Ministry of Health. RESULTS: The age structure is very
      similar in the 1993 sample and in the 1991 Census data, however, there is a
      remarkably lower proportion of women 15-19 years of age in the 1997 sample.
      According to the marital status, the 1997 sample has a higher proportion of women
      living in partner-strip and divorced women. The 1997 sample has a higher
      proportion of women with only one child and there were fewer women with 4 and
      more children. Also the proportion of women with secondary education with higher
      school certificate was higher in the later sample. CONCLUSION: This part of the
      study evaluate a changes in four demographic characteristics of women of
      reproductive age, because these changes could influence the reproductive health
      indicators (contraception, induced abortions), which are the subject of further
      analysis.

PMID- 10953477
TI  - [Ultrasonography of the funneling of the urethra].
AB  - OBJECTIVE: The objective of the study was to evaluate possibilities of using
      contrast substances during transperineal urogenital ultrasound examination.
      DESIGN: Prospective, pilot study. SETTING: Department of Obstetrics and
      Gynaecology, 1st Medical Faculty, Charles University, Prague. METHODS: 28 women
      with stress of incontinence were included in the study. For all women, position
      and mobility of the bladder neck and funneling of urethra was evaluated by
      transperineal ultrasound examination, and, subsequently, by ultrasound contrast
      substance examination. Both examinations were compared. During the Valsalva
      manoeuvre, the contrast substance enters the proximal urethra and allows a more
      exact diagnosis of urethra funneling than in the case of examination without the
      use of contrast substance. When using contrast substance, funneling was diagnosed
      in 25 patients compared to 7 patients subjected to common transperineal
      examination. CONCLUSION: Using contrast substance significantly improves
      visualisation of urethra funneling and opens new possibilities in diagnosing
      stress incontinence.

PMID- 10953478
TI  - [Personal experience with thermoablation of the endometrium with the Thermachoice
      balloon catheter].
AB  - OBJECTIVE: To evaluate our first experience with thermal balloon therapy of
      abnormal uterine bleeding. DESIGN: Prospective study. SETTING: Department of
      Obstetrics and Gynaecology, 1st Medical Faculty, Charles University, Prague.
      METHODS: Ten procedures of balloon thermal endometrial ablations were performed
      between November 1998 and February 1999. From ten patients with abnormal uterine
      bleeding, 4 patients with concomitant polymorbidity (sclerosis multiplex,
      hypertension, hepatopathia, pyelonephritis) where more invasive intervention was
      not recommended or was contraindicated. Treatment entailed controlled heating of
      intrauterine balloon. Local anaesthesia-paracervical block with analgosedation
      was employed in 50% of procedures and general anaesthesia was employed in 50% of
      cases. Follow up after 3, 6, 12, 24 months is required. Success was defined as
      the reduction of menses to eumenorrhoea or less. RESULTS: Preliminary results
      after 6 months follow up are successful in 100%; in 5 (50%) cases we recorded
      amenorrhoea, in 2 (20%) cases hypomenorrhoea and in 3 (30%) cases eumenorrhoea.
      CONCLUSION: Thermal balloon endometrial ablation appears to be safe due to its
      minimal invasivity especially in patients with abnormal uterine bleeding with
      concomitant polymorbidity.

PMID- 10953479
TI  - [Ovarian stromal hyperthecosis and concurrent endometrial carcinoma of the
      uterus].
AB  - The authors describe the case of a 50-year old patient with a hypertension, who
      was sterile and obese. She presented with the clinical diagnosis of "malignant
      corporal polyp". On microscopical examination we found an endometroid
      adenocarcinoma of the endometrium with focal squamous differentiation associated
      with bilateral stromal hyperthecosis of the ovaries. Stromal hyperthecosis of the
      ovaries is often associated with oestrogen and androgen hypersecretion
      (virilismus), obesity and hypertension. Owing to these well known features we
      assume that the endometroid adenocarcinoma of the uterus was caused by ovarian
      hyperthecosis.

PMID- 10953480
TI  - [Premature ovarian failure syndrome].
AB  - OBJECTIVE: A review of the premature ovarian failure syndrome. DESIGN: Review
      article. SETTING: Department of Obstetrics and Gynaecology, Charles University,
      Prague, Czech Republic. SUMMARY: The incidence of premature ovarian failure (POF)
      is reported to vary between 0.9% and 3%. Most often, the syndrome is manifested
      by amenorrhoea followed by typical postmenopausal symptoms caused by oestrogen
      deficiency. The only diagnostic criteria of the syndrome are FSH levels > 40 IU/L
      obtained twice at least one month apart in women below 40 years of age. The cause
      of the disease remains obscure in most women. The most often identifiable cause
      is an autoimmune disorder of the follicular apparatus with a genetic cause
      established less frequently. All POF women should be examined for other possible
      autoimmune diseases and women below 30 years of age should have their karyotype
      identified. Despite the possibility of preserved follicular activity, the
      probability of pregnancy is very low in those women. Induction of ovulation is
      virtually ineffective. The diagnosis of POF is a clear indication for long-term
      oestrogen-progestagen replacement therapy even in the absence of symptoms of
      oestrogen deficiency.

PMID- 10953481
TI  - [Surgical treatment of endometriosis].
AB  - Ovarian endometriotic cysts with adhesions and rectovaginal endometriosis are
      absolute indications for laparoscopic surgery. Peritoneal minimal endometriosis
      is considered a relative indications for surgery by many experts. The discussion
      is ongoing and more randomized studies are necessary. Ureteral and intestinal
      endometriosis are indicated for surgery in cases of deep infiltration of the
      ureteral or intestinal wall. In some cases the GnRH analogue (gonadotropin
      releasing hormone) can be given as neoadjuvant chemotherapy; after it interval
      endometriotic debulking is possible. In the case of endometriosis we must apply
      the same strict rules as in oncology especially as regards negative or positive
      histological findings.

PMID- 10953482
TI  - [Statistics for physicians--part II].
AB  - Authors present a series of papers describing basic statistical methods used in
      biomedical research and publications. Part two deals with the normal distribution
      and logarithmic transformation of data together with the simple strategy for data
      description in groups of different type of data distribution.

PMID- 10953483
TI  - [The spectrum of lipids in the intrauterine growth retarded fetus and in the
      parents].
AB  - OBJECTIVE: The aim of this study was to determine the relationship between the
      parameters of individual serum lipids and the degree of intrauterine growth
      retardation (IUGR) of the fetus. The lipid levels were compared in fetuses with
      IUGR and in eutrophic fetuses and it was determined in which studied variable
      IUGR newborns differ from healthy newborns. METHODS: The group under study
      consisted of 53 pregnant women in whom IUGR of the fetus was diagnosed by
      ultrasound during pregnancy. The control group consisted of 26 women who gave
      birth to eutrophic newborns. The cases in the control group were chosen by the
      method of matched control so that the results could be statistically evaluated in
      both groups at the same gestational age and at the same maternal age. In both
      groups blood samples from the umbilical cord were taken after delivery and the
      whole spectrum of lipid levels were evaluated (cholesterol-CH, triglycerides-TGA,
      high-density lipoprotein--HDL, low-density lipoprotein--LDL, Lp(a) lipoprotein,
      and apolipoproteins-ApoB, ApoAI, ApoE). The same parameters were evaluated in
      maternal and paternal blood samples. In several cases, intrauterine lipid levels
      of the fetus were determined by cordocentesis. The incidence of
      hyperlipoproteinemia in the families of both groups was surveyed. SETTING:
      Department of Obstetrics and Gynaecology, 1st medical Faculty, Charles
      University, Prague. RESULTS: There was a significant incidence of
      hyperlipoproteinemia in the families of the mothers in the group studied (chi
      square test: p < 0.001). In the mothers of the groups studied, there were
      statistically significant higher levels of HDL, LDL, and Lp(a) in comparison to
      the mothers in the control group. A significant dependence was determined between
      the levels of ApoAI and Lp(a) of the mothers and newborns. In the regression
      analysis of the dependence of lipid levels on the birth weight of the newborns, a
      statistical correlation was determined for the values of ApoB and Lp(a).
      CONCLUSION: The more increased the intrauterine growth retardation of the fetus
      and the lower its birth weight in relation to its gestational age, the higher its
      lipid levels, specifically apolipoproteins. Apolipoproteins are under genetic
      control and present a genetic risk for changes in the metabolism of cholesterol,
      hemocoagulation, and cardiovascular disease in adulthood.

PMID- 10953484
TI  - [Reproductive health in women in the Czech Republic 1993-97. II. Contraception].
AB  - THE AIM OF THE STUDY: To identify changes in reproductive health status as
      consequence of changes in the system of health care and social affairs. THE AIM
      OF THIS PART OF STUDY: To identify changes in use of different contraceptive
      methods among women of reproductive age in the Czech Republic. TYPE OF THE STUDY:
      Retrospective comparative epidemiological study. NAME AND ADDRESS OF THE
      INSTITUTION: Institute for the Care of Mother and Child Praha 4--Podoli. METHODS:
      Comparison of data on contraceptive use among women of reproductive age from two
      representative national surveys (see the first part of the study). Analysis was
      done by demographic characteristics using programs developed by the Centers for
      Disease Control, Atlanta, Georgia, U.S.A. RESULTS: There was no difference in
      proportion of women using one of four methods of contraception in 1993 sample and
      in 1997 sample (60%), however, there was change in their order. While the most
      frequently used method in 1993 sample was withdrawal (18.6% out of 60% of
      contraceptive users) and the pills were the last used method (7.7%), the order in
      1997 sample was just opposite (pills 23.9%, withdrawal 6.7%). The proportion of
      condom and IUD users remained practically unchanged. With decline of withdrawal
      users, the proportion of other three methods increased from 37% to 52% (out of
      60% of contraceptive users). The hormonal contraception was preferred method
      among women with higher education, while condom was the most popular among women
      with occasional intercourse or women with different partners (single women, women
      without children, divorced women). CONCLUSION: The withdrawal and condom users
      were the more frequent methods of contraception in 1993 sample versus two other
      methods (ratio 2:1), while this has changed in 1997 sample in favor of IUD and
      hormonal contraception users (ratio 3:2). We could conclude that the
      responsibility for contraception has been transferred from men to women.

PMID- 10953485
TI  - [The effect of follicular fluid pH on the quality and number of oocytes produced
      in the in vitro fertilization program].
AB  - OBJECTIVE: The aim of our study was to evaluate the role of follicular fluid pH
      as the marker of quality of the human oocyte in the IVF treatment efforting to
      predict and to enhance the effect of IVF treatment: oocyte quality, fertilization
      rate, cleavage rate, implantation rate. DESIGN: Prospective study. SETTING:
      Center of assisted reproduction, Department of Gynaecology and Obstetrics,
      Medical Faculty of Charles University, Pilsen. METHODS: The pH of the follicular
      fluid was measured in 147 IVF cycles. The oocyte quality was evaluated according
      to the oocyte-cumulus-cells complex morphology during the ovum pick up, according
      to fertilization rate, number of recovered oocytes and recovery rate. RESULTS:
      The lower pH of the follicular fluid correlated with significant higher
      occurrence of the cycles with more then half of oocyte-cumulus complexes with
      normal mature morphology (P = 0.026) and correlated with significant higher
      occurrence of cycles with fertilization rate more then 10% (P = 0.033).
      CONCLUSION: There was found a lower pH of the follicular fluid in the IVF cycles
      where the quality of oocytes was higher.

PMID- 10953486
TI  - [Use of cryopreserved sperm in the microagglutination test].
AB  - OBJECTIVE: The aim of this study was to find out the behavior of sperm
      cryopreserved in microagglutination test (TAT). METHODS: TAT using native sperm
      pertains to the screening methods in spermagglutinating antibodies. Spermatozoa
      cryopreserved in egg-yolk medium, just in seminal plasma or in the commercial
      made medium--Medi-Cult (Denmark) were used in this study. SETTING: Department of
      Gynaecology and Obstetrics, Institute of Clinical Immunology and Allergology
      Medical Faculty of Charles University, Pilsen. RESULTS: 367 tests were performed
      together. It includes 108 examinations with native spermatozoa, 59 with
      spermcryopreserved in egg-yolk medium, 109 with spermcryopreserved just in
      seminal plasma and 91 in Medi-Cult medium. The correspondance of results with
      native and cryopreserved sperm was found in 24% for egg-yolk medium, in 69% for
      seminal plasma and in 77% for commercial medium Medi-Cult. CONCLUSION: The
      results show that spermcryopreservation in Medi-Cult medium or just in the
      seminal plasma are able to be used in TAT for detection of spermagglutinating
      antibodies.

PMID- 10953487
TI  - [Prenatal cytogenetic diagnosis at the Department of Medical Genetics GENNET
      Klimentska].
AB  - OBJECTIVE: Analysis of data from prenatal cytogenetic studies performed during 10
      years. DESIGN: Retrospective analysis of cytogenetic results. SETTING:
      Cytogenetic laboratory, Department of Clinical Genetics GENNET, Prague. METHODS:
      Cytogenetic analysis of cultivated amniotic cells. RESULTS: 180 chromosomal
      pathologies, including 110 numerical and 70 structural, were diagnosed in 5743
      samples of amniotic fluid. Relatively high number of structural aberrations was
      found also in groups of patients examined because of increased maternal age,
      abnormal values of biochemical markers and abnormal ultrasound findings.
      Chromosomal abnormalities in individual groups of patients, risk figures for de
      novo balanced structural aberrations, additional marker chromosomes and some
      mosaic findings as the management following the prenatal diagnosis of this
      abnormalities are discussed. CONCLUSION: On the basis of the great number of
      familiar structural aberrations in our material is recommended to pay attention
      to the detection of such anomalies also in groups of patients where numerical
      chromosomal changes are namely expected.

PMID- 10953488
TI  - [Hysteroscopic polypectomy versus fractionated curettage in the treatment of
      corporal polyps--recurrence of corporal polyps].
AB  - OBJECTIVE: The evaluation of hysteroscopy contribution in the treatment of
      endometrial polyp. The evaluation of the risk of endometrial polyp recurrence.
      DESIGN: Prospective clinical study. SETTING: Department of Obstetrics and
      Gynecology of Medical faculty and Faculty Hospital, Pilsen. METHODS: Two groups
      of patients were followed. Group I had 81 patients (30 premenopausal and 51
      postmenopausal) that underwent hysteroscopical polypectomy followed by diagnostic
      hysteroscopy in 6-12 months. Group II consisted of 100 patients (36 premenopausal
      and 64 postmenopausal) that underwent fractional curretage with histological
      diagnosis of endometrial polyp. These patients were checked by diagnostic
      hysteroscopy in up to 12 months. Presence of endometrial polyp during diagnostic
      hysteroscopy and a relation of its recurrence or persistence to a type of
      preceding procedure, risk factors and histological findings during the first
      procedure were evaluated. RESULTS: 11 (13.5%) cases of an endometrial polyp were
      recorded in hysteroscopical controls in group I. 46 (46%) cases of an endometrial
      polyp were recorded in group II. Recurrence of the endometrial polyp was revealed
      only in one case of atrophic endometrium and in no case of atrophic endometrial
      polyp. CONCLUSION: Hysteroscopical polypectomy showed considerably better results
      in the treatment of endometrial polyp comparing to fractional curretage. The
      recurrence risk of endometrial polyp is expected in a case of presence of an
      abnormal proliferative activity or hyperplasia both in the endometrial polyp and
      the surrounding endometrium.

PMID- 10953489
TI  - [Ultrasonic evaluation of paravaginal defects before and after surgical treatment
      in women with urinary stress incontinence].
AB  - OBJECTIVE: The aim of our study was to analyze whether transabdominal and
      introital ultrasonography can accurately identify paravaginal defect associated
      with GSI (Genuine stress urinary incontinence) and to determine the changes after
      paravaginal defect repair. DESIGN: Prospective randomised clinical study.
      SETTING: Department of Obstetrics and Gynecology, Charles University, Prague,
      Czech Republic. METHODS: Sixteen women with GSI, who had previously not undergone
      anti-incontinence surgery were involved. Their average age was 52 years, average
      weight 71 kg and average parity 2.0. Within vaginal examination our attention was
      focussed on the diminution of sulsus superioris vaginae during Valsalva maneuver.
      The bladder of a patient in supine position was filled with 300 ml of sterile
      saline. Than a 5 MHz curved array probe was used to assess the bladder neck
      mobility from the perineal approach, and the same probe was used from the
      abdominal approach to determine paravaginal defect and subsequently a vaginal
      probe from introital approach was used for the rest of the examination. After
      Burch colposuspension and paravaginal defect repair US scanning was performed 6
      till 8 days and 5 or 6 weeks after operation. RESULTS: We found significant
      differences in bladder neck position and mobility before and after the operation.
      In women with symptoms of GSI we found from abdominal approach unilateral or
      bilateral paravaginal defect in fifteen women. Unilateral defect was found on the
      right side six times and on the left side only once. In eight women the defect
      was bilateral. The introital approach obtained similar results, only in two
      patients with bilateral defect the examination concluded unilateral right defect.
      After the operation we did not find PVD in patients after paravaginal defect
      repair. We obtained worse results from vaginal examination, where preoperatively
      PVD was correctly determined (sensitivity) only in 82.6%. CONCLUSION: From our
      preliminary results we can suggest performing US scanning to conform paravaginal
      defect before anti-incontinence surgery and possibly adding to the Burch
      colposuspension paravaginal defect repair to correct cystourethrocele.

PMID- 10953490
TI  - [The factor V Leiden mutation in users of hormonal contraceptives].
AB  - OBJECTIVE: To assess the frequency of factor V Leiden in oral contraceptive users
      and to define possible anamnestic data that could predict the presence of factor
      V Leiden. METHODS: Between 1997 and 1998, 583 users of oral estrogen-progestin
      contraceptives with no history of thrombotic disease were examined. Factor V
      Leiden was assessed by PCR after isolating DNA from a peripheral venous blood
      sample. Among other factors, such things as a family history of thromboembolic
      disease, myocardial infarction and/or stroke in a first-degree relative were
      monitored. In 448 users cardiovascular complications were evaluated during six
      months of oral contraceptive use. The data were analyzed using a MS Excel
      program. P-values were assessed by pair-tests and chi-square tests. SETTING: 1st
      Department of Obstetrics and Gynecology of Medical Faculty, Masaryk University,
      Brno. RESULTS: Factor V Leiden frequency was 6.5% in the study group. There were
      no differences between carriers and others in age, body weight, body mass index
      and blood pressure. Carriers had significantly more frequently positive family
      histories of thromboembolic disease or myocardial infarction or stroke. There
      were no cardiovascular complications observed in a group of 448 users. The
      positive family histories of any of the above-mentioned conditions have high
      specificity (97-99%) and a negative predictive value (0.94) with a low
      sensitivity (2.6-15.8%) in predicting factor V Leiden presence. CONCLUSION: We
      found a relatively high incidence of Factor V Leiden among oral contraceptive
      users without a history of thrombotic disease. Through a positive family history
      of thromboembolic disease or myocardial infarction or stroke, we can predict a
      Factor V Leiden presence with high specificity but low sensitivity.

PMID- 10953491
TI  - [Psychosexual development and sex life of women with congenital adrenogenital
      syndrome].
AB  - OBJECTIVE: The aim of the study was to examine the psychosexual development and
      sexual life of 13 adult women with congenital adrenogenital syndrome. DESIGN: A
      clinical study. SETTING: Psychiatric clinic, Gynecological clinic and Sexological
      institute, Medical Faculty of the Charles University in Prague. METHODS: The
      examination was carried out using a structured interview and three tests: MF
      (Masculinity and feminity), SFW (Sexual function of women) and SAI (Inventory of
      sexual arousibility). RESULTS AND CONCLUSION: It was ascertained that only about
      one third of the patients were coitally active and that the first intercourse was
      delayed. The results of the questionnaire SFW were in 66% subnormal and an
      adequate sexual arousability was found only in 40% of examined persons (the test
      SAI).

PMID- 10953492
TI  - [Granulosa cell tumor--clinical group and literature review].
AB  - OBJECTIVE: To present a review of literature and to analyse a clinical
      retrospective series of patients with granulosa cell tumor. DESIGN: Retrospective
      study and review. SETTING: Department of Obstetrics and Gynaecology, First
      Faculty of Medicine, Prague, Czech Republic. METHODS: Retrospective analysis of
      age, stage, surgery, radiotherapy and chemotherapy, survival curve, number of
      recurrences and time to recurrence. Literature and information database (Medline
      1997-1999) review. RESULTS: In a group of 43 patients the median of age was 53.5
      years. 83.7% of cases were in a stage I. There were two duplicate tumors in a
      series. Conservative surgery was performed in 9/43 cases, 5 of them were
      reoperated on. The most frequent chemotherapy regimens were platinum
      cyclophoshamide and BEP (bleomycin, etoposide, platinum). The 5-year overall
      survival was 86% and specific survival 90.7%. There were 3/43 recurrences, median
      time to recurrence was 22 months. CONCLUSION: A good prognosis of a patient with
      granulosa cell tumor requires a precise histopathologic examination, an adequate
      surgery and a comprehensive clinical analysis of a case to evaluate an indication
      of adjuvant therapy. Concentration of patients in oncogynaecological centres is
      advisable. A careful follow-up because of a risk of late recurrences is
      necessary.

PMID- 10953493
TI  - [Fertility after chemotherapy of gestational trophoblastic disease].
AB  - OBJECTIVE: To evaluate subsequent pregnancy experience in patients following
      chemotherapy for malignant form of gestational trophoblastic disease. DESIGN:
      Retrospective clinical study. SETTING: Slovak Center of Trophoblastic Disease,
      Bratislava, Slovak Republic. METHODS: There were evaluated subsequent pregnancy
      experiences in 38 patients after chemotherapy for malignant form of gestational
      trophoblastic disease registered in Slovak center of gestational trophoblastic
      disease. Histological and cytogenetical analysis of all placentas after
      deliveries and material from curettage specimens after miscarriages, abortions
      and ectopic pregnancies were performed. RESULTS: 11 women conceived following
      successful chemotherapy of gestational trophoblastic disease became pregnant a
      total 19 times. Out of them there were 9 full-term deliveries, 2 spontaneous
      abortion, 1 ended in ectopic pregnancy and 7 pregnancies were terminated in
      therapeutic abortion. Cytogenetical analysis was successful in 7 to 10
      reproductive losses with normal karyotype in all analysed cases. CONCLUSION:
      Patients after successful chemotherapy of gestational trophoblastic disease have
      a normal reproductive outcome.

PMID- 10953494
TI  - Hemostasis using tissue glue in laparoscopy: discussion and review.
AB  - OBJECTIVES: To discuss the usefulness of tissue glue and TachoComb (TC), a new
      hemostyptic agent which combines the advantages of two reliable hemostyptic
      products-collagen fleece and fibrin glue in local hemostasis during laparoscopy.
      SETTING: Department of Gynecology and Obstetrics, Endoscopic Training Centre,
      Hospital Kladno. DESIGN: Review. METHODS: Analysis of literary and clinical data.
      RESULTS: In recent years, collagen fibers, gelatin sponges, oxidized cellulose
      and fibrin glue has been developed, which are now widely used in postoperative
      hemostasis in laparoscopy. An efficient use of these preparations shortens the
      duration of intervention procedures and reduces patient strain. CONCLUSIONS:
      Clinical studies demonstrate that hemorrhage from damage tissue important pelvic
      structures can be successfully arrested and controlled using the laparoscope to
      apply tissue glue. At Czech study, sixteen patients have been effective treated
      with collagen-fibrin agent during laparoscopic operations. The elimination of
      hemorrhages after primary laparoscopic electrosurgery and the effectiveness of
      this drug have been successfully tested.

PMID- 10953495
TI  - [An innovation in the Report on the Parturient].
AB  - Introduction of the form "Report on Parturient" in 1991 as a part of National
      Health Information System and annual national analyses of the data contributed to
      the improvement of obstetrical care. Such improvement impacted on decrease of
      maternal and perinatal mortality. Advances in obstetrical diagnostic procedures
      during last 8 years and new WHO form Basic Information Sheet (BIS), recommended
      for use in Europe for unified recording of selected indicators of perinatal care,
      created need to innovate the "Report on Parturient". The 5-year development of
      the WHO BIS under the international WHO Project OBSQID (two workers from the WHO
      Collaborating Center of the Institute for the Care of Mother and Child
      contributed to that activity) is described. Also, the collaboration with the
      Office of Health Statistics and Information, which resulted in innovation of
      "Report on Parturient" is mentioned. The new form "Report on Parturient"
      compatible with the WHO BIS will come to use the 1st of January 2000.

PMID- 10953496
TI  - [Analysis of maternal mortality in the Czech Republic in 1997 and 1998].

PMID- 10953497
TI  - [Follicular fluid and its properties].

PMID- 10953498
TI  - [Teratogens during pregnancy].
AB  - OBJECTIVE: To sum up the knowledge of the influence of substances in the external
      environment on the development of the human embryo/fetus during exposure at
      various periods of intrauterine life. TYPE OF STUDY: Summary. SETTING: Department
      of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University,
      Prague. METHODS: Compilation of data from scientific literature. RESULTS: An
      overview of the main groups of teratogenic substances among the physical,
      chemical, biological and metabolic teratogens. Their relationship to
      morphological malformations, anomalies and functional defects are described.
      CONCLUSION: A summary of the principles/basics of care of a pregnant woman using
      medication before or during pregnancy and the possibility of evaluating the
      individual reproductive risk during preconception and prenatal exposure to
      teratogenic substances.

PMID- 10953499
TI  - [Statistics for physicians--part III].
AB  - Authors present a series of papers describing basic statistical methods used in
      biomedical research and publications. Part three deals with statistical
      hypotheses, type I and type II errors, one-sided or two-sided tests. Finally, the
      most frequent types of testing the differences are described.

PMID- 10953500
TI  - [Gynecologic operations in patients after kidney and liver transplantation--case
      report].
AB  - OBJECTIVE: To give an overview of the complications associated with the post
      transplantation period which thus presents an increased risk for subsequent
      gynecological surgery and also for the postoperative period. To determine the
      criteria and conditions under which these operations may be performed with
      relative safety. TYPE OF STUDY: Case report. SUBJECT OF STUDY: Described surgical
      treatment of gynecological diseases in three patients after liver and kidney
      transplantation. CONCLUSION: A summary of the principles/basics of patient care
      after surgery for gynecological indications with a prior organ transplant in ther
      patient's history. These patients should undergo surgery in hospitals with a high
      quality of professional care as well as high quality equipment and cooperation
      among the specialists from the various medical fields involved.

PMID- 10953502
TI  - [Role of nonenzymatic glycation and oxidative stress on the development of
      complicated diabetic cataracts].
AB  - Eye lens cataract can develop by various mechanisms the details of which are not
      completely known. Increased level of glucose in patients with diabetes mellitus
      represents one of the factors accelerating cataract development. As the lens does
      not depend on insulin, cataract formation is induced by hyperglycaemia both in
      IDDM and NIDDM patients. Glucose attacks free aminogroups of proteins and
      glycation products are formed by multistep non-enzymatic reactions. We can
      discriminate early and late products. The latter are often called as advanced
      glycation endproducts (AGE). They can accumulate inside the lens and interfere
      with its optical properties. With regard to the fact that glycation reactions are
      accompanied by autooxidation reactions, the overall process is usually referred
      to as glycoxidation. Free radical oxidations of membrane lipids give similar
      products as do glycation reactions, and there is synergy between these two
      pathways. Development of eye cataract is accompanied by a decrease in lens
      antioxidant capacity. A new class of glycation inhibitors has been observed
      recently. They are called Amadorins and they have therapeutic potential in the
      cataract treatment.

PMID- 10953501
TI  - [Catastrophic types of epilepsy in early development].
AB  - Epilepsy is characterized by recurrent seizures of various etiopathogenesis and
      history. Hyperexcitability and hypersynchronization of neurons are essential
      features for the development of epileptiform activity. About 80% of patients can
      achieve remission using adequate therapy. There is an important difference
      between the developing brain in children and the adult brain in terms of
      morphology and function. In spite of the great therapeutic advance, there is a
      group of developmental epileptic syndromes with a poor prognosis--catastrophic
      epilepsies in childhood (involving early epileptic encephalopathies, West
      syndrome, and Lennox-Gastaut syndrome). The mechanisms of epileptogenesis in
      several types of seizures were determined thanks to the animal model research.
      Additionally, animal models of seizures make possible testing of antiepileptic
      drugs. Unfortunately, in catastrophic epilepsies in childhood, the search for the
      adequate animal model still continues.

PMID- 10953504
TI  - [Ethics and legal aspects of use of animals in experimental studies].
AB  - Animals have been used in research since ancient times already. Originally they
      were used for anatomical and physiological demonstrations. Later they started to
      be used by another fields--microbiology, toxicology and pharmacology, surgery.
      Animal use is frequently implicated in relation to ethical problems. Actual view
      is based on biocentric opinion, which part is formed by "three R's" concept-
      reduction, replacement, refinement in animal use. Laws applied to animal use in
      Czech Republic are anchored in Law on Animal Protection and Decree of Ministry of
      Agriculture on Experimental Animal Use and Breeding. Owing to militant behaviour
      of organisations involved in animal rights movement there is no adequate
      propagation of experiments, which are ethically and juridically clear and which
      particularly help mankind in a struggle against diseases.

PMID- 10953503
TI  - [Nitric oxide and regulation of pulmonary vessels].
AB  - One of the most important differences between the pulmonary and systemic
      circulation is a considerably lower blood pressure and hemodynamic resistance in
      the pulmonary circulation. After the discovery of the endogenous vasodilatator,
      nitric oxide (NO), it had been assumed that pulmonary vasculature is
      characterized by a high tonic NO production, which might contribute to the low
      basal tone of these vessels. Incapacity to maintain this high NO production would
      then lead to the development of pulmonary hypertension. However, numerous studies
      summarized in this review gradually proved that, in reality, this simple scheme
      does not apply. Healthy pulmonary vessels usually produce only relatively small
      amounts of NO. In pulmonary hypertension, NO synthesis increases. The rise in
      pulmonary artery pressure is partly blunted by this protective mechanism, at
      least until the pulmonary endothelium (a major source of NO) is damaged by the
      permanent and severe elevation of the intravascular pressure.

PMID- 10953505
TI  - [Experimental characteristics of eye movements].
AB  - Presented article summarises results of the experimental analysis of the
      horizontal eye movements evoked by light stimuli. The measured variable is the
      potential difference recorded between electrodes placed on the skin surface at
      the temporal canthus and the middle of the forehead. Our database includes more
      than 350 records and their brief characteristics. Eye movements registration and
      detailed analysis might become one of undemanding screening and diagnostic
      methods.

PMID- 10953506
TI  - [Evaluation of heart rate variability and its usefulness].
AB  - The article presents a review of the method of the evaluation of the heart rate
      variability using spectral analysis and of the cardiovascular regulation
      evaluation using cardiovascular tests. It refers about the application in
      physiological research. The importance of the heart rate variability examination
      will increase in the future according to the sensitivity, noninvasivity and
      precision.

PMID- 10953507
TI  - [Hormonal regulation of gene transcription--nuclear hormone receptors as ligand
      activated transcription factors].
AB  - Nuclear hormone receptors regulate gene transcription upon recognizing specific
      regulatory sequences--hormone responsive elements (HRE) in gene promoters,
      enhancers, and silencers. Receptors for sexual and adrenal steroid hormones,
      thyroid hormone, retinoic acid and vitamin D, as well as an extensive group of
      orphan receptors, all exhibit strong homology in structural and functional
      organization of the molecule and they form together the nuclear receptor
      superfamily. While classical steroid receptors dissociate upon activation an
      inhibitory hsp-complex, dimerize and then are able to bind cognate HRE and
      activate transcription, thyroid and retinoid receptors as well as the vitamin D
      receptor bind the HRE in question constitutively and activation is represented by
      dissociating a corepressor and recruiting a coactivator. Similar mode of action
      applies also for orphan receptors. Some of recently resolved orphan receptors are
      activated by immediate products of metabolism; the metabolism of cholesterol
      relies in great part on selective activation of a particular orphan receptors by
      a particular cholesterol metabolite.

PMID- 10953508
TI  - [Na+/Ca+ exchange: structure, mechanism, regulation and function].
AB  - The Na+/Ca2+ exchange is a plasma membrane system for the countertransport of Na+
      and Ca2+ ions. The system can transport Ca2+ both into and out of the cell and
      therefore it plays a crucial role in the calcium homeostasis. The system works in
      electrogenic way (3 Na+ are exchanged for 1 Ca2+) and thus it influences the
      electrogenic properties of excitable cells. Due to new techniques of
      electrophysiology and molecular biology a lot of information about transport
      mechanism, regulation and possible physiological and pathophysiological roles of
      the exchanger was accumulated. This review summarises new findings and shows
      progress in this attractive field of biological research.

PMID- 10953509
TI  - Some reflections on empathy and reciprocity in the use of countertransference
      between supervisor and supervisee.
AB  - Reciprocity refers in its general meaning to a mutual give and take. It is a
      background feature of all productive supervisory relationships. In this essay I
      want to bring it into the foreground. I will describe it by contrasting
      supervision and analysis. For, in my view, that is exactly what reciprocity is in
      the supervisory relationship: it is an attitude of mind in which the supervisor
      performs the task of differentiating internally the supervisory from the analytic
      vertex, in the context of the asymmetry of the supervisory relationship.

PMID- 10953510
TI  - Desert wanderings: pathways for whole, broken and shattered psyches.
AB  - This paper challenges an implicit assumption of analytical psychology that
      centred, mandalic images express psychical wholeness in an optimal fashion across
      cultures and eras. I suggest that liminal, bardo-like eras, such as our 'post
      modern' one, constellate complex, antithetical and ec-centric images, which are
      process-oriented and which encompass wholeness and fragmentation, conjunction and
      disjunction, thus holding and expressing actual individual and collective
      experience. In our era, we inhabit unfolding states of wholeness, brokenness and
      fragmentation. Images of wholeness, emerging spontaneously from the unconscious,
      may reflect part or all of these contradictory realities. Examples of such
      antithetical Self-images are developed from the ancient midrashic traditions of
      the rabbis; from Jung's contemporary exposition of Pauli's 'world-clock' dream;
      from Kepler's discovery, at the dawn of modernity, that the planets circled the
      sun in ellipses rather than circles; and from a clinical illustration.

PMID- 10953511
TI  - Reliability and validity of scores from the Singer-Loomis Type Deployment
      Inventory.
AB  - This paper focuses on the Singer-Loomis Type Deployment Inventory (SL-TDI), which
      is an alternative to the Myers-Briggs Type Indicator (MBTI). The SL-TDI utilizes
      a continuous, non-forced choice format and therefore is a more accurate
      representation of Jung's personality theory of psychological types. The purpose
      of the study reported here is to evaluate the reliability and validity of scores
      from the SL-TDI. Specifically, the goals were to (a) provide estimates of the
      internal consistency of SL-TDI scores; (b) evaluate the divergent validity of SL
      TDI scores by examination of their relationships with the scores on a social
      desirability responding measure; and (c) examine the test-retest stability of
      scores from the SL-TDI. Strong support was found for both the reliability and
      validity of SL-TDI scores.

PMID- 10953512
TI  - Orpheus and Eurydice: a creative agony.
AB  - The archaic story of the Thracian musician Orpheus and his bride Eurydice is
      heard first as an ancient myth of marriage and death, wedding and separation. The
      mixture of expectation and dread in its sentiments is sounded still today in the
      contemporary wedding songs and funeral laments of the Mediterranean and the
      Balkans. Similar sequences of engagement and withdrawal, ascent and descent,
      change and metamorphosis are found in the adventures and vicissitudes of other
      mythic figures. Its premise of the soul's transmigration and its promise of
      psychic transformation inspired the religious ruminations and philosophic
      speculation of many centuries. The shifting keys in the songs of Orpheus and the
      cries of Eurydice score the shocking emotions of epiphanal moments, the creative
      'agon', and a depth psychological passage. With its crescendos and denouements,
      the Orpheus/Eurydice phenomenon suggests the range of experience as one both
      engages reality and reaches toward meaning.

PMID- 10953513
TI  - What is analysis?
AB  - This paper attempts to discern a ground for doing depth psychological work in
      times of disappearance, loss and the absence of the gods. Through the poetry of
      Friedrich Holderlin, and to a lesser extent, Rainer Maria Rilke, it seeks to
      discover the significance of fragmentation and conflagration in the
      manifestations of both psyche and the post-industrial landscape we inhabit. What
      does the 'death of god' mean for our notions of symbol and self and for the
      practice of psychotherapy and psychoanalysis? How do we understand our daily
      clinical work in the context of ruin, holocaust and despair?

PMID- 10953514
TI  - Misunderstanding Jung: the afterlife of legends.
AB  - F. X. Charet's article, 'Understanding Jung: recent biographies and scholarship',
      is full of errors and legends. In this article, I demonstrate the tendentiousness
      of his criticisms of the historical work of Eugene Taylor and myself concerning
      Jung's linkages with the subliminal psychology of Theodore Flournoy, William
      James, and F. W. H. Myers, and the fallaciousness of his criticism of my claim
      that Memories, Dreams, Reflections was not Jung's autobiography.

PMID- 10953515
TI  - Simply not simple.

PMID- 10953516
TI  - Question questioned.

PMID- 10953517
TI  - TMD debate.

PMID- 10953518
TI  - A moving account.

PMID- 10953519
TI  - Early orthodontic care.

PMID- 10953520
TI  - Statistical tests.

PMID- 10953521
TI  - Periodontal treatment.

PMID- 10953523
TI  - Working drafts of human genome announced.

PMID- 10953522
TI  - Women in dentistry.

PMID- 10953524
TI  - Saliva test for hepatitis C on the horizon.

PMID- 10953525
TI  - Schilder to receive Alpha Omega Achievement Award.

PMID- 10953526
TI  - Tobacco or oral health: past progress, impending challenge.
AB  - BACKGROUND AND OVERVIEW: A number of significant events and research findings
      during the past 15 years have led to the dental profession's growing involvement
      in tobacco-use intervention activities. The author presents an overview of events
      and people responsible for the progress in furthering the cause of dentistry's
      activism in tobacco-use prevention and control. CLINICAL IMPLICATIONS: Dentistry
      has led the health professions in establishing a protocol for the prevention of
      tobacco use, a health behavior that causes or contributes to various oral
      diseases and adverse conditions. Dentists practicing in the 21st century cannot
      ignore patients' tobacco use. Treatment prognoses for periodontal therapy, wound
      healing, dental implants, cosmetic treatments and cancer therapy all are
      compromised by patients' tobacco use. Dentists must know what to do and say to
      prevent patients' tobacco use and aid patients in its cessation.

PMID- 10953528
TI  - Tobacco-use control and cessation resources.

PMID- 10953527
TI  - Tobacco-use prevention and cessation: dentistry's role in promoting freedom from
      tobacco.

PMID- 10953529
TI  - High-quality research and patient care: an overview of clinical trials.
AB  - BACKGROUND: One of the responsibilities of the dental profession is to protect
      and advance the well-being of the public through research of new pharmaceuticals
      and devices. The objective of this article is to present information about the
      scientific and regulatory process involved in the design and execution of
      randomized clinical trials. CONCLUSIONS: Dentists willing to serve as
      investigators in clinical trials--from Phase 1 to Phase 2 or Phase 3--need to be
      aware of the two main documents that contain the majority of guidelines and
      regulations governing clinical research: Title 21 of the U.S. Code of Federal
      Regulations and the guidelines for good clinical practice put forth by the
      International Conference on Harmonisation. CLINICAL IMPLICATIONS: Advancements in
      the frontiers of oral health science and the development of safe, innovative and
      effective treatment modalities are often the result of high-quality clinical
      research that is conducted by dental professionals. Knowledge of the research
      process, professionalism, scientific integrity and a detailed execution of the
      research plan are all required elements for a successful outcome.

PMID- 10953531
TI  - James Beall Morrison: the visionary who revolutionized the practice of dentistry.
AB  - BACKGROUND AND OVERVIEW: For centuries, dental patients sat on makeshift
      contraptions or modified straight-backed chairs, which took a toll on the health
      of both patient and dentist. In addition, the lack of a suitable drill retarded
      the development of restorative dentistry, allowing minimum care for only a tiny
      segment of the population. One farseeing American dentist, James Beall Morrison,
      changed all that in the 1870s with his innovative, fully adjustable chair, which
      made sitdown dentistry possible. Moreover, his monumental invention of the foot
      powered drill allowed dentists to place restorations that were theretofore
      impossible. Dentists the world over became able to treat patients more
      comfortably and satisfactorily, and with less stress to themselves. CLINICAL
      IMPLICATIONS: A newly discovered collection of letters in the Smithsonian
      Institution to Morrison from colleagues in London provides insight into how
      collaboration between inventor and user helped bring about great changes in the
      way dentistry is practiced. These letters also shed light on what dentistry was
      like one and one-quarter centuries ago, how far dentistry has come and what
      changes may be forthcoming.

PMID- 10953530
TI  - Oral pemphigus vulgaris preceding cutaneous lesions: recognition and diagnosis.
AB  - BACKGROUND: Pemphigus vulgaris, or PV, is a potentially life-threatening illness
      that manifests itself initially in the mouth in the majority of patients.
      Paradoxically, it is less commonly recognized when it involves lesions on the
      oral mucosa rather than on the skin. CASE DESCRIPTION: This article describes the
      clinical presentation of 42 cases of oral PV evaluated and diagnosed by dentists.
      Emphasis is placed on the common distribution and appearance of oral PV lesions
      and diagnosis of the disease. CLINICAL IMPLICATIONS: The dentist has a unique
      opportunity to recognize the oral presentation of PV and contribute to an early
      diagnosis and, therefore, an improved treatment outcome.

PMID- 10953532
TI  - Managing incomplete tooth fractures.
AB  - BACKGROUND: The author presents an evidence-based protocol for the diagnosis and
      treatment of incomplete tooth fractures. It is designed to help dentists
      recognize fractures, distinguish between restorable and nonrestorable fractures,
      and follow a rational approach to treatment. OVERVIEW: An incomplete tooth
      fracture is a frequently encountered problem that dentists need to assess
      carefully to arrive at the correct treatment decision. The author presents a
      review of representative literature corroborating the assertions made in the
      evidence-based protocol. Treatment approaches are presented for each of two major
      fracture types. CLINICAL IMPLICATIONS: Dentists need to be aware of the classic
      symptoms of incomplete tooth fracture, the methods used in formulating a
      differential diagnosis, criteria for determining pulpal status and restorability,
      iatrogenic factors involved in the etiology of incomplete fracture, and the
      consequences of inadequate diagnosis or treatment.

PMID- 10953533
TI  - Single-operator sealant placement made easy.

PMID- 10953534
TI  - Diagnosing and comanaging patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome, or OSAS, is a common, but
      underdiagnosed, disorder that potentially is fatal. It is characterized by
      repetitive episodes of complete or partial upper airway obstruction leading to
      absent or diminished airflow into the lungs. These episodes usually last 10 to 30
      seconds and result in loud snoring, a decrease in oxygen saturation, and chronic
      daytime sleepiness and fatigue. The obstruction is caused by the soft palate,
      base of the tongue or both collapsing against the pharyngeal walls because of
      decreased muscle tone during sleep. Potentially fatal systemic illnesses
      frequently associated with this disorder include hypertension, pulmonary
      hypertension, heart failure, nocturnal cardiac dysrhythmias, myocardial
      infarction and ischemic stroke. CLINICAL IMPLICATIONS: The classic signs and
      symptoms of OSAS may be recognizable by dental practitioners. Common findings in
      the medical history include daytime sleepiness, snoring, hypertension and type 2
      diabetes mellitus. Common clinical findings include obesity; a thick neck;
      excessive fat deposition in the palate, tongue (enlarged) and pharynx; a long
      soft palate; a retrognathic mandible; and calcified carotid artery atheromas on
      panoramic and lateral cephalometric radiographs. CONCLUSIONS: Dentists cognizant
      of these signs and symptoms have an opportunity to diagnose patients with occult
      OSAS. After confirmation of the diagnosis by a physician, dentists can
      participate in management of the disorder by fabricating mandibular advancement
      appliances and performing surgical procedures that prevent recurrent airway
      obstruction.

PMID- 10953535
TI  - Will pit-and-fissure sealants be improved?

PMID- 10953536
TI  - Do restorations made of amalgam outlast those made of resin-based composite?

PMID- 10953537
TI  - Impact of older adults on private dental practices, 1988-1998.
AB  - BACKGROUND: A 1988 study indicated that older adults made up a substantial
      portion of regular patients seen in private dental practices. A follow-up study
      was conducted in 1998 to track changes over the decade in the participating
      practices. METHODS: The authors collected data from respondents to the 1988
      survey again in 1998. The authors received complete data from 41.7 percent of the
      original respondents who still were practicing at their 1988 addresses. Dentists
      kept a log of all procedures provided in their practices in one day. The authors
      attributed values of services in both years, using a 1997 national estimate of
      fees. RESULTS: The authors found that the percentage of office visits, services
      provided and patient expenditures attributed to patients 65 years of age or older
      exceeded the percentage of the population in that age group. In four of the five
      age groups in which patients had the highest mean expenditures, patients were 60
      years of age or older. Patients 60 years of age or older accounted for 28.8
      percent of all patient expenditures, a 12.1 percent increase from 1988.
      Longitudinal analyses indicated that between 1988 and 1998, dentists 40 years of
      age or older experienced increases of 30.3 to 64.3 percent in the proportion of
      visits, services and expenditures by patients 65 years of age or older.
      CONCLUSIONS: The results of this investigation illustrate the importance of older
      adults to dental practices. Data from the practices of dentists who participated
      in both surveys show increases in the percentage of total dental visits, total
      services provided and total patient expenditures attributed to older adults.
      CLINICAL IMPLICATIONS: Older adults continue to have a disproportionate and
      positive impact on the surveyed dental practices and their financial well-being.
      Dentists should reevaluate the accessibility of their practices to this
      population. Rather than waiting for the practice to "age," dentists may want to
      structure their practices in ways that appeal directly to older adults and work
      to even better understand the needs and preferences of older patients already in
      their practices.

PMID- 10953538
TI  - Resin cements and postoperative sensitivity.

PMID- 10953539
TI  - Some insurers must follow 'fair procedures' when terminating a provider,
      California court rules.

PMID- 10953540
TI  - Chronic dietary Cu(2+)-deficiency alters cholecystokinin signal transduction in
      isolated rat pancreatic acini.
AB  - This study tested the hypothesis that diminished exocrine pancreatic function
      observed in Cu(2+)-deficient rats is associated with alterations in the
      cholecystokinin (CCK) signal transduction pathway. Male Sprague-Dawley rats were
      maintained on either a control diet (11 ppm Cu2+) or a Cu(2+)-deficient diet
      containing 6000 ppm triethylenetetramine tetrahydrochloride. For the duration of
      the study rats had free access to water and food. After 4 weeks, rats were
      sacrificed and pancreatic acini isolated for measurement of amylase content,
      cholecystokinin-stimulated amylase release and total inositol phosphate
      formation. Plasma Cu2+ levels were significantly (P < 0.05) decreased in rats on
      a Cu(2+)-deficient diet (19.2 +/- 3.4 micrograms Cu2+/dL), compared with the
      control diet (77.0 +/- 3.5 micrograms Cu2+/dL). Both amylase content of
      pancreatic acini and total CCK-8-stimulated amylase release were significantly
      decreased in Cu(2+)-deficient rats. In addition, Cu(2+)-deficient rats exhibited
      a decrease (153.5 +/- 30.9%) in the magnitude of CCK-8-stimulated total inositol
      phosphate formation compared with control rats (220.8 +/- 11.9%). Moreover, CCKA
      receptor affinity on pancreatic membranes was not significantly altered by Cu(2+)
      deficiency, while CCKA receptor density was significantly (P < 0.05) decreased in
      Cu(2+)-deficient rats. The addition of Cu2+ to the binding assay of Cu(2+)
      deficient rats did not restore receptor density to control values. The data
      demonstrates that adequate dietary intake of Cu2+ is important to maintain the
      functional integrity of the exocrine pancreas.

PMID- 10953541
TI  - Selective COX-2 inhibitors and gastrointestinal mucosal injury: pharmacological
      and therapeutic considerations.
AB  - It is well recognized that nonsteroidal antiinflammatory drugs (NSAIDs) induce
      gastrointestinal (GI) ulcerations, perforation and bleeding, which clearly limit
      their therapeutic value. The recent introduction of NSAIDs with selective
      cyclooxygenase-2 (COX-2) inhibitory effect is a major pharmacologic milestone in
      therapeutics. Selective COX-2 inhibitors exhibit considerable dissociation
      between their antiinflammatory/analgesic action and their GI toxicity. However,
      from a therapeutic consideration, there are still several unresolved and
      confusing issues with these drugs such as: the pharmacologic classification of
      the COX-2 selectivity; therapeutic value as antirheumatic/analgesic drugs;
      potential toxicity in patients at risk for the development of ulcer-related
      complications or patients with inflammatory bowel disease and potential renal
      toxicity. Although existing clinical efficacy studies with celecoxib and
      rofecoxib, two selective COX-2 inhibitors, were associated with considerably
      lower ulcerogenic rates when compared with nonselective NSAIDs, there are no long
      term outcome studies with these drugs similar to the MUCOSA trial performed with
      misoprostol. Furthermore, the selectivity of COX-2 inhibitors appears to be
      specific to the stomach and duodenum but not the kidney. While awaiting
      additional long term studies with selective COX-2 inhibitors, we recommend
      instituting prophylactic therapy with misoprostol in patients at risk for the
      development of ulcer related complications. In conclusion, we believe that the
      introduction of selective COX-2 inhibitors will revolutionize the treatment of
      pain and inflammation. However, additional basic and clinical studies are
      required to address the pharmacologic and therapeutic uncertainties for this
      class of drugs.

PMID- 10953542
TI  - The role of race/ethnicity in the epidemiology of esophageal cancer.
AB  - Esophageal cancer is known for its marked variation by geographic region, race,
      ethnicity, and gender. In the United States, incidence rates for African
      Americans are more than twice the rates for whites, and rates for whites exceed
      those for Hispanics, Asian Americans, and Native Americans. In addition,
      decreases in incidence of squamous cell carcinoma of the esophagus and increases
      in esophageal adenocarcinoma have been observed over the past several decades.
      This paper will explore the role of race/ethnicity in the epidemiology of
      esophageal cancer and the extent to which alcohol, tobacco, diet, and social
      class may contribute to racial/ethnic differences in incidence and mortality.

PMID- 10953543
TI  - Pregnancy and inflammatory bowel disease: current management.
AB  - Inflammatory bowel disease primarily affects adolescents and young adults,
      presenting management concerns for obstetricians caring for these women during
      pregnancy. Interdisciplinary care by the obstetrician and gastroenterologist and
      selection of individual courses of management produce pregnancy outcomes that
      approach those of an unaffected population. Routine medical management using
      glucocorticoids, metronidazole, and asacol derivatives as well as more aggressive
      therapy using immunomodulators azathioprine and 6-mercaptopurine are shown to be
      of low risk to the fetus. Effective medical management greatly reduces need for
      surgical intervention during pregnancy. An understanding of current management
      perspectives assures positive pregnancy outcomes for mother and infant.

PMID- 10953544
TI  - A survey of ocular complaints in postmenopausal women.
AB  - Aging patients often complain about chronic ocular irritation, which is commonly
      related to dryness of the eyes. To determine the effect of hormone replacement
      therapy (HRT) on ocular complaints and tear production, we compared these
      parameters in postmenopausal women who were taking or not taking HRT. A
      questionnaire was administered to determine the number of ophthalmic complaints
      of 79 women who were postmenopausal at least 1 year (mean, 22 +/- 13.5 years) and
      were not using any ophthalmic drops or medication known to contribute to dry
      eyes. A Schirmer test with anesthesia was performed on each subject to quantify
      tear production. We found that the number of ophthalmic complaints of women
      taking HRT was statistically fewer (P = 0.015) than women not taking HRT. Women
      taking HRT for 5 years or longer had statistically fewer complaints and greater
      tear production, as measured by the Schirmer test, than women taking HRT for 5
      years or less. The study concluded that women taking HRT have significantly fewer
      ocular complaints than women not taking HRT. HRT may help alleviate symptoms
      related to ocular dryness in postmenopausal women.

PMID- 10953545
TI  - [Minimally invasive surgery--a new era in the development of surgery?].

PMID- 10953546
TI  - [Inhibitory activity of blood group antigens M and N in inhibition of virus
      hemagglutination reactions of influenza viruses].
AB  - INTRODUCTION: M and N blood group antigens demonstrate inhibitory activity in
      inhibition reaction of viral hemagglutination with some influenza virus strains,
      with help of N-acetylneuraminic acid (sialic acid) which occurs in glycophorins
      on the red blood cells surface, and represent specific hemagglutunation receptors
      and substrate for action of influenza virus neuraminidase. MATERIAL AND METHODS:
      Reactivity of human O red blood cells with MM and NN phenotypes is established in
      inhibition reaction of viral hemagglutination by influenza virus A2 Singapore,
      with intention to fortify possibility of using human red blood cells in viral
      hemagglutination, to determine their reactivity in titration, retitration of
      hemagglutinins and inhibition reaction of hemagglutination. The aim of
      investigation was to describe destinations between different red blood cells in
      view of speed of reaction and receptor capacity. Material included 69 samples of
      sera from persons infected with influenza virus, among them 32 samples were
      positive with titres 1/80 and more. RESULTS: Reactivity of erythrocytes with MM
      and NN phenotypes in titration of hemagglutinins of influenza virus A2 Singapore
      in which base is viral hemagglutination is identical, because there are no
      statistically significant differences of average geomaterical levels of antibody
      titers. Enzymatically derived red cells by papain, which do not contain M and N
      blood group antigens, not cause viral hemagglutination phenomenon, because they
      sediment in all dilutions. Reactivity of red blood cells with MM and NN
      phenotypes in retitration of haemagglutinins and inhibition reaction of
      hemagglutination is identical, because there are no statistically significant
      differences in results with two kinds red blood cells. DISCUSSION: Results of
      investigation revealed that the reactivity of O human red blood cells different
      in MN phenotype is identical in regard to speed of reaction and receptor capacity
      in titration, retitration and inhibition reaction of viral hemagglutinatination
      and also showed that they demonstrate viral hemagglutination phenomenon in
      contrast with papainised red blood cells which do not contain M and N blood group
      antigens, which indirectly means that M and N blood group antigens contain
      receptors for influenza virus. CONCLUSIONS: Human red cells with MM and NN
      phenotypes cause viral hemagglutination phenomenon with influenza virus A2
      Singapore, and could be used in routine virusological diagnostic procedures. O
      blood group red cells (MM and NN) in reaction of viral hemagglutination result
      identically in view of speed of reaction and receptor capacity, and have the same
      impact on result of this reaction. Enzymatically derived red cells by papain do
      not cause viral hemagglutination phenomenon, because they do not contain
      receptors for viral hemagglutinin on red cell membrane surface, which are
      hydrolazed by papain. Receptors for influenza virus on red cell membrane surface
      are a component part of M and N blood group antigens which are destroyed by
      papain.

PMID- 10953547
TI  - Frequency estimation of the gene alleles for genodermatoses in the population of
      Vojvodina.
AB  - Genodermatoses are hereditary skin disorders or anomalies. The authors had
      investigated the frequency of genes, species and clinical forms of hereditary
      dermatoses in Vojvodina including age and sex distribution. The experimental
      group was selected by random sampling of the diseased of genodermatosis and/or
      genetic diseases at the Clinic of Dermatology and Venereology and Institute for
      Children and Adolescents in Novi Sad. The experimental group included 152 cases,
      and that made simultaneously the experimental and positive control group in
      relation to the diseased population with genodermatoses and/or genetic diseases
      in Vojvodina. In the investigation we applied the following methods: family
      history taking including genealogy; dermatoglyphic examination; screening tests
      in medical genetics; cytogenetic analysis of patient's karyotype;
      histopathological analysis of the material obtained by skin biopsy;
      dermatovenereological, genetic and dysmorphologic examination of skin diseases by
      analysis of dysmorphologic signs on the skin using a special computer program-
      POSSUM (Pictures of Standard Syndromes and Undiagnosed Malformations).
      Application of non-parametric statistics and Log-linear analysis, revealed that
      there is no statistically significant difference between the experimental group
      and the group with genetic diseases in population of Vojvodina. The obtained
      incidence of genodermatoses and/or genetic diseases was computed by "Hardy
      Weinberg's principle". These methods of genetic population investigations give
      possibilities for valid incidence estimation of the diseases and frequency of the
      gen allele's for genodermatoses and/or genetic disorders and syndromes in defined
      population. Our results of investigation of the incidence genodermatoses in our's
      population showed significantly increased values in relation to literature data
      for the same hereditary disorders.

PMID- 10953548
TI  - Sentinel node biopsy in breast cancer.
AB  - Regional lymph node involvement is the most important prognostic indicator in
      most solid tumors. Lymph nodes first to receive the lymphatic flow from the
      peritumoral region are called sentinel nodes. Extirpation methodology of these
      nodes is rather short (around 10 years) and is related to the following names:
      Cabanas, Morton, Uren, Berman, Glass, Alex, Cragg.... There are two visualization
      methods of sentinel nodes: detecting dyes (isosulfan blue or patent-blau V) and
      radioactive detection (technetium-Tc-99m-antimony-sulfide, sulphur-colloid or
      human albumin). Scintigraphy is usually performed 24 hours prior to surgery,
      whereas staining immediately before operation. Extirpated nodes are
      histopathologically examined and then findings are compared with the findings of
      other axillary nodes which require obligatory dissection. Results of great
      studies (Veronesi, Paganelli) show that under precise criteria it would be
      possible to form a group of patients, prepared for breast cancer surgery, in whom
      axillary lymph dissection could be avoided.

PMID- 10953549
TI  - [Reversible left ventricular dysfunction in coronary disease (part one):
      myocardial stunning].
AB  - INTRODUCTION: The concept of myocardial stunning has been proposed by Braunwald
      and Kloner in early 1980's and is defined as transient postischemic myocardial
      dysfunction that persists after reperfusion, despite the absence of irreversible
      damage and restoration of normal or near normal coronary flow. Thus, the hallmark
      of stunned myocardium is the mismatch between coronary flow and myocardial
      function. MYOCARDIAL STUNNING: The two most plausible hypotheses used to explain
      the pathogenetic mechanisms of myocardial stunning are calcium and oxyradical
      hypotheses. According to the first one, myocardial stunning is the result of
      impaired calcium homeostasis caused either by calcium overload or decreased
      responsiveness of myofilaments to calcium. The oxyradical hypothesis postulates
      that generation of free oxygen radicals depresses myocardial function after the
      ischemic episode. The exact mechanism is unknown, but it is probably due to
      extreme reactivity of oxyradicals that bind to some cellular components,
      impairing membrane permeability and function of various cell organelle. Stunned
      myocardium can be seen in numerous clinical situations in which myocardial
      ischemia has been followed by reperfusion. These include: coronary artery bypass
      surgery, acute myocardial infarction, stable, unstable and variant angina,
      percutaneous transluminal coronary angioplasty and cardiac transplantation.
      DISCUSSION AND CONCLUSION: In majority of these situations, stunned myocardium is
      usually well tolerated. However, there is a group of high-risk patients in whom
      prolonged myocardial dysfunction due to stunning can cause serious hemodynamic
      instability, which requires pharmacological and/or mechanical support. Therefore,
      in order to avoid these situations, some authors have suggested that stunned
      myocardium should be prevented, rather than treated. Since stunned myocardium is
      by definition reperfused, with normal or near normal coronary flow, treatment is
      reserved only for those patients in whom stunned region is large enough to cause
      low cardiac output and hypotension. Revascularisation is usually unnecessary;
      however, there are situations in which episodes of repetitive stunning cause
      chronic myocardial dysfunction along with hibernated myocardium, when myocardial
      revascularization would be beneficial.

PMID- 10953550
TI  - [Clinical importance and pathogenic mechanisms of insulin resistance in chronic
      renal insufficiency (part I): insulin resistance in patients with chronic renal
      insufficiency].
AB  - INTRODUCTION: This paper presents new investigations of abnormal insulin action
      in patients with chronic renal failure. Reduced tissue sensitivity to insulin
      action and the effects of the impairments on carbohydrate, protein and lipid
      metabolism have important pathophysiological implications in the genesis of the
      uremic syndrome. We analyzed confounding factors of reduced insulin sensitivity
      and potential sites of insulin resistance. INSULIN RESISTANCE IN HUMANS: Insulin
      resistance is associated with a number of metabolic and vascular abnormalities
      known as "syndrome X" or metabolic syndrome. Other features include obesity,
      particularly truncal distribution, glucose intolerance and non-insulin-dependent
      diabetes mellitus (NIDDM), hypertension, a specific dyslipidemia with raised
      triglyceride concentrations and a high low-density lipoprotein: high-density
      lipoprotein ratio, and hyperuricemia. These features, are all associated with
      accelerated atherogenesis and cardiovascular disease, the main cause of premature
      mortality. Some genetic (mutations affecting postreceptor signalling pathways)
      and environmental factors that could contribute to insulin resistance are
      discussed. INSULIN RESISTANCE IN CHRONIC RENAL FAILURE: The most prominent
      metabolic disturbance in uremic patients is insulin resistance due to a post
      receptor defect. Insulin secretion is also impared, because the pancreatic beta
      cell response to hyperglycemia is blunted. Insulin clearance by renal and
      extrarenal mechanisms is reduced. POSSIBLE SITES OF INSULIN RESISTANCE IN
      TERMINAL RENAL FAILURE: Increase in hepatic glucose production or impaired
      hepatic glucose uptake were overestimated. Impaired glucose uptake by peripheral
      tissues, primarily muscle and adipose tissue, has been extensively studied, and
      there is abundant evidence in patients with chronic renal failure. Decrease in
      renal glucose production would lead to a decrease in glucose appearance in
      circulation and decrease of insulin sensitivity. CONCLUSION: Cellular basis for
      insulin resistance in uremic patients is, however, unknown. It is now recognized
      that insulin-stimulated glucose transport in skeletal muscles and in other
      peripheral tissues is reduced. Although the majority of uremic patients are
      insulin resistant and about half of them are glucose intolerant, they are rarely
      diabetics. But, there are clinical implications of abnormal insulin metabolism in
      uremia. Cardiovascular complications are the most important consequences and
      significant cause of mortality in these patients.

PMID- 10953551
TI  - [Molecular genetics in the hereditary form of long QT syndrome].
AB  - INTRODUCTION: Progress in molecular genetics contributed to the discovery of
      pathophysiologic mechanisms of hereditary diseases as well as better diagnostics
      and efficient therapy. Several defective ge- nes have been discovered on
      different chromosomes (3,4,7,11 and 21 pair of chromosomes), and also their
      relationship with some types of LQTS (long QT syndrome). Gene dysfunction leads
      to the dysfunction of ion channels, which consequently causes prolonged duration
      of repolarization in cardiac muscle. These changes are manifested on
      electrocardiogram with prolonged duration of QT interval (over 0.44 sec.).
      Familial forms of LQTS are inherited as autosomal dominant (Roman Ward syndrome)
      and autosomal recessive (Jervell Lange-Neilsen syndrome). The final form of LQTS
      is defined even with hearing loss. Clinical survey: malignant ventricular
      arrhythmia, syncope and sudden death. MOLECULAR ARCHITECTURE OF VOLTAGE-GATED ION
      CHANNELS: Duration of voltage-gated ion can be regulated by Na and K channels.
      Cardiac action potential plateau is an indicator of the balance of inward and
      outward ionic currents. During this process of voltage-gated potential two
      currents are activated: depolarized inward current (it happens in the Na
      channels) and repolarized outward current (it happens in the K channels). Na
      channels are polypeptides incorporated in cell membrane. Their main function is
      to control excitability in myocardial cell. They consist of two subunits: alpha
      and beta. Class Ib of anty-arrhythmics (Lidocaine, Mexiletine and Tocainide) as
      well as Diphenylhydantoin blocks Na channels in the state of inactivation, in
      fact, during the depolarization of the cell. For controlling the cardiac voltage
      gated potential the most important are voltage-sensitive K channels. For
      appearance of K ions delayed refraction of K channels (Kv) is of importance.
      Depending on the velocity of activation, Kv are divided into two groups: channels
      with rapid activation (Kvr) and channels with slow activation (Kvs). By
      activation of these delayed rectification channels (Kv) beta agonists shorten the
      action potential of the heart. GENETIC ASPECTS OF LQTS: Five loci which are
      connected with Romano Ward's familial form of LQTS have been described up to now.
      Specific mutant gene is responsible for function of K channels and it is located
      on short branch (part) of the 11-th pair of chromosome 11p15.5 (KVLQT-LQT1), long
      branch of the 7-th pair of chromosomes 7q35-36 (K- HERG-LQT2), as well as on the
      21-st pair of chromosome (KCNE1-LQT5). Defective gene which is responsible for
      the function of Na channels is located on the short branch of chromosome 3p21-24
      (SCN5A-LQT3). The gene which is located on the long branch of the 4-th pair of
      chromosome 4q25-27 (LQT4) has not been examined sufficiently. Persons with Jevell
      Lange-Neilsen syndrome inherit pathological allele from both parents (KvLQT1 or
      LQT5-minK). CONNECTION BETWEEN ION CHANNELS AND GENE MUTATION: Among all genes
      which are responsible for LQTS the most examined one is the so-called HERG gene
      located on the 7-th pair of chromosome (LQT2). Mutation of this gene leads to
      reduction in strength of outward K currents or to the dysfunction of K channel
      proteins. Mutant gene causes so-called missense mutation, in fact wrong change of
      amino acid in the protein chain. Among all described LQTS the most frequent and
      the most malignant form is LQT1. In 99% cases psychophysical stress can cause
      arrhythmia, syncope or sudden death. LQT3 and LQT5 are very rare. CONCLUSION:
      Genetic screening in LQTS patients provides discovery of risk population which
      demands anti-arrhythmic therapy with beta-blockers. A lot of arguments speak in
      favour of genetic screening in cases with LQTS. It is considered that if the
      diagnosis is known, genetic testing is not necessary, but it is useful. Moreover,
      it is obligatory in symptomatic cases as well as in those with suspected
      diagnosis of LQTS.

PMID- 10953552
TI  - [Periapical surgery of the molars].
AB  - INTRODUCTION: If loss of a great number of teeth occurs, one molar in the lateral
      segment is of great importance. Contemporary techniques and materials provide
      extremely successful conservative treatment of pulpal diseases and apical
      periodontitis. In some cases, however, surgery is indicated. INDICATIONS:
      Indications for periapical surgery used to be a matter of double standards. If
      periapical surgery is indicated in incisors, it is performed without delay, but
      if it is indicated in molars, it is often exchanged for extraction. Surgical
      access in the region of upper and lower molars is specific in regard to much more
      frequently operated incisors due to anatomic structures at the surgical site.
      Canal filling techniques, implants, endodontic surgical procedures are of
      importance and can provide better healing. High quality canal filling is
      condition sine qua non in treatment of apical periodontitis. It is performed
      prior surgery, by conventional orthograde endodontic techniques, during surgery
      by orthograde technique and/or retrogradely. Implants provide better bone healing
      and are recommended in surgery of molar apex. Surgical packing has numerous
      advantages (better psychological and mechanical care). CONCLUSION: Good knowledge
      of anatomy and surgical techniques is a pre-requisite for molar apicoectomy.
      Careful establishment of indications and good relations with the patient provide
      good prognosis of this therapeutic method.

PMID- 10953553
TI  - [Transvaginal sonography of the postmenopausal endometrium].
AB  - INTRODUCTION: The most frequent symptom suggesting endometrial pathology is
      uterine bleeding. Each postmenopausal uterine bleeding requires fraction
      explorative curettage and histopathologic examination of the material obtained
      from the cervical canal and uterine cavity. The aim of this study was to estimate
      the efficacy of ultrasonography as a non-invasive method in detection of
      endometrial pathology in postmenopausal women, and to find out whether its more
      frequent use could safely decrease the number of curettages in detection of these
      conditions. MATERIAL AND METHODS: A prospective investigation has been performed
      in postmenopausal women not menstruating for more than a year, and who reported
      to the Department of Obstetrics and Gynaecology in Novi Sad for uterine bleeding
      during 1996 and 1997. Each woman underwent ultrasonographic examination by
      vaginal probe of 5 MHz and fraction curettage, whereas the samples from cervical
      canal (if obtained) and from uterine cavity were sent to histopathologic
      examination to the Institute of Pathology in Novi Sad. Standard statistical
      methods have been used for the analysis of the results. Validity of the applied
      ultrasonographic method in detecting endometrial pathology has been estimated by
      calculation of its sensitivity and specificity. RESULTS: A satisfactory
      visualisation of the endometrium has been obtained in all 35 examined cases. The
      thinnest endometrium was 1 mm wide and the thickest one was--25 mm. The fraction
      curettage has been used to obtain material from the cervix in 2 cases and from
      the uterine cavity in 35 cases. In our patients with uterine bleeding, who were
      in the postmenopause for 13 years on average, endometrial atrophy was recorded in
      17.14%, endometrial polyp in 11.43%, endometrial hyperplasia in 22.86%,
      endometrial adenocarcinoma in 42.86% and uterine sarcoma in 5.71%. There were 2
      false negative ultrasonographic findings (2 cases of endometrial hyperplasia) and
      sonographic thickness less than standard versus 2 false positive cases
      (endometrium thicker than the limit value, 7 and 14 mm, with no real pathology)
      which showed that the sensitivity of the investigated method was 93.10% and the
      specificity was 66.66%, if the limit value for the thickness of endometrium was 3
      mm. DISCUSSION: Ultrasonographic thickness of endometrium means maximum double
      thickness in longitudinal plane, i.e. the distance of the opposite bordering
      surfaces of endometrium and myometrium. The procedure of measurements of
      endometrial thickness is simple in most cases. Most authors agree that there is a
      positive correlation between the thickness of endometrium and its pathological
      conditions. The most often used limit values are 3 and 4 mm. Higher limit values
      of endometrial thickness increase the sensitivity of the method even to 100%, but
      negatively affect its specificity making this method inadequate as a screening
      method for endometrial carcinoma. Many authors insist on introducing other
      criteria for evaluation of the endometrium i.e. for taking its thickness as the
      only criterion. Ultrasonography does not provide a completely safe
      differentiation between benign hyperplasia and endometrial carcinoma. CONCLUSION:
      The transvaginal sonography is an efficient and acceptable, noninvasive method
      for early detection of endometrial pathology in postmenopausal women. The
      thickened endometrium during menopause is the most significant ultrasonographic
      criterion implicating its pathology. The vaginosonographically measured thickness
      of 3 mm and less, gives a relatively safe prediction of endometrial atrophy,
      whereas the thickness above 3 mm requires explorative curettage and
      histopathologic examination of the endometrium, no matter if the woman has or has
      not uterine bleeding. (ABSTRACT TRUNCATED)

PMID- 10953554
TI  - [Thyroid gland nodules registered at the Endocrinology Department of the Medical
      Center in Prokuplje].
AB  - INTRODUCTION: Thyroid nodules are often found in clinical practice. General
      population prevalence is about 4%, whereas in women it is over 6%. The basic
      disorder of cell kinetics of thyroid tumors is inappropriate growth response to
      corresponding thyroid-stimulating hormone (TSH) concentration. MATERIAL AND
      METHODS: At the Endocrinology Department of Medical Centre in Prokuplje, during
      the first year of practice (1997), 430 patients with thyroid gland disease were
      registered, both male and female belonging to different age groups. Patients were
      examined in regard to: sex, age, heredity, symptoms. Basic laboratory analyses
      were done with the aim to establish inflammatory syndromes: sedimentation,
      leukocytes, differential blood picture, cholesterolemia and fibrinogenemia;
      hormones of thyroid glands (T3, T4, TSH) with corresponding radioimmunoassay
      (RIA) technique. In the aim of identifying the nodules in the thyroid gland and
      perceiving nodular features, an ultrasound examining was done and scintigraphy of
      thyroid gland if necessary. Scintigraphy was done with radioactive technicium-99
      mTc. RESULTS: From the total number of registered patients (430) with thyroid
      gland disease, nodules were found in 172 glands (40%). The presence of thyroid
      nodules is more frequent in women (91.3%). The average age of thyroid gland
      patients is 50.33 years, of which men aged 52 and women aged 50.17. The following
      risk factors are stated as the most frequent: chronic stress 58.13%, consuming
      goiter substances 46.51% (cabbage, kale, sulphonamide). Swollen thyroid gland-
      goiter occurred in 105 cases (61.07%), whereas in 120 patients (69.32%) normal
      function was registered. In most cases the nodules are solitary 90 (52.32%). In
      71.01% of patients cold nodules were found. In 36.04% of patients nodules were 1
      to 1.9 cm in size. The greatest number of patients--83 (36.61%) complained of
      heart disorder as a symptom. 2.9% out of 172 patients with thyroid nodules
      underwent operation. DISCUSSION: The obtained data mostly coincide with the
      findings of other authors. Trbojevic found thyroid nodules 3 to 4 times more
      often with women. In this research it is ten times more frequent. Bozovic
      especially pointed out the existence of inflammatory factors, mentioned in this
      group in 12.97% cases. We can not neglect the hereditary factor either--11.62%
      which is not clearly defined by other authors [1,2,3]. According to Trbojevic,
      solitary nodules are present in 60% of cases. In this research the number is
      52.32%. Cold nodules are found in 71.07% (according to Trbojevic 90%). Only 2.9%
      of patients were operated, which is not enough if we follow all the medical
      indications. CONCLUSION: Out of the total number of patients (430) with thyroid
      gland disease, 172 patients (40%) with nodular changes in thyroid glands have
      been found. Far more frequent (90%) are women aged 51 to 60 years (after
      menopause). The number of operated patients with thyroid nodules is insufficient.

PMID- 10953555
TI  - [Comparison of preoperative and postoperative hemodynamic parameters in
      replacement or reconstruction of the mitral valve in ischemic dilated
      cardiomyopathy].
AB  - INTRODUCTION: Ischemic mitral insufficiency is a clinical syndrome described as a
      consequence of the coronary artery disease where the basic problem is blood
      regurgitation between the left ventricle and left atrium following mitral annulus
      dilatation. Mitral regurgitation occurs in different degrees during the natural
      evolution of the ischemic heart disease. The main reason for the existence of
      mitral regurgitation is global deterioration in the left ventricle geometry as a
      consequence of myocardial infarction or/and left ventricle dilatation. Surgical
      correction of this problem is possible by simultaneous correction of mitral
      insufficiency (repair or replacement) and complete myocardial revascularisation.
      MATERIAL AND METHODS: Complete hemodynamic monitoring was followed by Swan-Ganz
      catheter including: central venous pressure, mean pulmonary artery pressure,
      pulmonary capillary wedge pressure, cardiac output, cardiac index and pulmonary
      vascular resistance. All surgical procedures were performed in extracorporeal
      circulation (ECC) with membrane oxygenator using moderate systemic hypothermia
      and transseptal surgical approach to mitral valve. Hemodynamic parameters were
      followed before and after ECC, immediately after surgery and during the first 48
      hours after operation in the intensive care unit. In 88 patients posterior
      semicircular annuloplasty by N. Radovanovic was performed whereas in 13 patients
      mitral valve replacement was done. RESULTS: There is a great, statistically
      significant hemodynamic improvement after the surgical procedure and during the
      continuous 48 hours monitoring in the intensive care unit no matter if mitral
      repair or replacement was done. No statistically significant difference was
      recorded between these two groups considering that the hemodynamic improvement is
      very similar. DISCUSSION: Simultaneous surgical procedures, including myocardial
      revascularization, mitral and usually consecutive tricuspid insufficiency
      correction, are a very common surgical problem with higher operative risk than
      isolated coronary bypass procedures. In 88 cases where mitral reconstruction was
      possible, posterior semicircular reductive annuloplasty was performed. Thus
      mitral annulus area reduction is achieved preserving its physiologic shape and
      avoiding rigidity. Mitral valve replacement includes implantation of the latest
      generation of bileaflet valve prosthesis and operative technique that preserves
      subvalvular apparatus to maintain myocardial contractility as much as possible.
      This policy and also good immediate postoperative care, improve the hemodynamic
      status in both groups. CONCLUSION: All hemodynamic parameters followed by ECC and
      48 hours in the intensive care unit were significantly improved no matter whether
      mitral reconstruction or replacement was done. There is no statistically
      significant difference in hemodynamic parameters and clinical improvement between
      these two groups. Carefully chosen operative tactic and techniques as well as
      good preoperative and postoperative care may explain these very good results.

PMID- 10953556
TI  - [Effect of prolactin on the regulation of osmotic processes across the
      fetoplacental membranes in vitro].
AB  - INTRODUCTION: The aim of this investigation was to point to the influence of
      minerals and total osmolality on regulation and secretion of prolactin in
      decidual tissue of the placenta and the role of prolactin in regulation of
      osmotic processes across the fetoplacental membrane. MATERIAL AND METHODS:
      Explants for the tissue culture have been obtained from pregnant women with
      normal pregnancy and delivery, between the 277 and 282 days of gestation. The
      investigation consisted of 4 repeated experiments. The parietal decidua and the
      corresponding chorion were separated from the amnion, rinsed in salt solution and
      cut into explants 0.2 g of weight. After a 2-hour period of preincubation in the
      control medium, 12 explants were incubated in the media of altered mineral and
      osmotic properties, whereas the 13-th in the control medium. Concentrations of
      prolactin following the 3-hour incubation in the medium was estimated by
      immunoenzymologic procedures. RESULTS: During the 3-hour incubation, the control
      explants secreted on average 75.4 +/- 5.23 micrograms/l of prolactin in the
      experiment repeated 4 times. The changes of Na+, Cl-, K+, Mg++, P- and HCO3-
      concentrations and of the total osmolality have not significantly influenced the
      synthesis of prolactin. In the medium with no Ca++, the value of secreted
      prolactin was 26.7 +/- 3.34 micrograms/l (p < 0.001); increase of the Ca++
      concentration has not influenced the synthesis of prolactin. In the medium with
      increased concentration of H+ (pH = 7.00), the prolactin concentration was 50.9
      +/- 2.9 micrograms/l (p < 0.001). CONCLUSION: The minerals--Na+, Cl-, K+, Mg++, P
      , HCO3- and the total osmolality do not significantly influence the synthesis of
      prolactin in decidual-chorionic tissue. Certain quantities of Ca++ and optimal
      concentration of H+ are necessary for the synthesis of prolactin (PRL).

PMID- 10953557
TI  - [Clinical examination in open fractures of the frontal bone].
AB  - INTRODUCTION: Fractures of the frontal bone most often occur with injuries: in
      traffic accidents, at work, at home, falls on stairs or slippery surfaces, in
      sport accidents, hoof injuries, etc. They are mostly seen within combined
      injuries, much less often as isolated. METHODS AND RESULTS: There were no
      patients under the age of 20; two were in their thirties, three each in their
      forties and fifties, and one patient in his sixties. Sex distribution: seven
      males and two females. Seven patients were injured in traffic accidents, and two
      working at home. DISCUSSION: Four of nine X-rays, although technically valid, did
      not reveal fracture lines on the frontal bones. In these cases the fracture was
      diagnosed by surgical exploration during the treatment of the soft tissue
      injuries of the frontal region. We must therefore point to the importance of
      surgical exploration of each, even the slightest injury of the soft tissues of
      the frontal region, so that the fractures of the frontal bone are not overlooked.
      Standard X-rays must be interpreted as a supplementary diagnostic procedure, but
      cannot be considered as absolutely reliable, since the lines can be obscured due
      to the thickness of the bone structures. The revision was made via the fronto
      orbital passage. The mucosae of the posterior wall was intact in five cases,
      while four cases had a fracture of the interior wall as well, without dislocation
      of fragments. We preserved the sinus cavities of five patients with only frontal
      wall injuries, while obliteration was performed in four cases due to the fracture
      of the interior wall. CONCLUSION: We have ascertained that standard radiography
      is an unreliable diagnostic procedure and, especially in case of minor injuries
      of the frontal bone, surgical exploration of the injured region is an imperative,
      as the only reliable method of excluding fracture of the frontal bone, and this
      long-established principle cannot be abandoned in these cases either.

PMID- 10953558
TI  - [Mycotic disease of the mucous membranes of the head and neck].
AB  - INTRODUCTION: Candidiasis is usually a superficial infection of the moist areas
      of the body and is generally caused by Candida albicans. Visceral infections
      occur in diabetes, lymphomas and leukemias, malnutrition, avitaminosis and they
      are associated with antibiotic, corticosteroid and immunosuppressive therapy.
      Candida albicans was isolated from middle ear inflammation. The diagnosis is made
      on the basis of microscopic appearance of colonies and characteristic smell.
      Candidiasis is successfully treated with nystatin, imidazol derivatives
      (fluconazole, ketoconazole and intraconazole), amphotericin B, 5-fluorocystosine
      and 1% iodine solution. CASE DESCRIPTION: This is a case report of a 46-year-old
      patient with a persistent nasal, sinus and ear infection of unknown origin. The
      patient first received antibiotic and steroid therapy and trepanation of the
      right maxillary sinus was performed. As the patient's condition aggravated with
      increase of temperature and bad laboratory findings, he was hospitalized.
      Radiography revealed a pathological process in both maxillary sinuses and both
      mastoids, so mastoidectomy and left maxillary sinus trepanation were performed.
      Histopathological examination of the right mastoid revealed a mould infection.
      The immunologic status pointed to hypogammaglobulinemia IgG. The following
      diseases were excluded: systemic diseases, blood diseases, Reiter's syndrome,
      AIDS, Hepatitis B, other viral diseases, toxoplasmosis, trichinellosis,
      borreliosis, typhus, paratyphus and exanthematous typhus. The diagnosis of
      candidiasis caused by Candida crusei and Candida kefyr was made on the basis of
      macroscopic and microscopic findings and biochemical identification. Ketoconazole
      was introduced (400 mg/per day) as well as high doses of vitamins and povidone
      iodine locally. After a period of remission the patient died due to myocarditis,
      sepsis, acute kidney failure associated with severe mucosal necrosis of the
      mouth, esophagus and throat. Differential diagnosis in fever of unknown origin
      must include the possibility of mycotic infection, whereas the therapy of mycotic
      diseases must include two antimycotics at the same time. DISCUSSION AND
      CONCLUSION: Candida albicans is often found in the oral cavity and skin as well
      as in intestines of 18% of healthy subjects. It is unknown why it causes clinical
      illness. Antibiotic therapy of bacterial infections enables candida colonization
      especially in immunosuppressed patients. In our patient two types were found:
      Candida krusei and Candida kefyr. It is of special importance to perform
      differential diagnosis in cases with fever of unknown origin in order to include
      the possibility of mycotic infections, whereas treatment of systemic fungal
      infections requires a team of physicians.

PMID- 10953559
TI  - [Hematologic characteristics of leishmaniasis].
AB  - INTRODUCTION: Leishmaniasis is a chronic infectious disease from the group of
      anthropozoonoses. It is caused by protozoa in the genus leishmania flagellate.
      There are five major foci of this disease in the world: India, Mediterranean
      countries, East Africa, South China and South America. Endemic regions in the
      Balkans are as follows: Montenegro, Macedonia, Herzegovina and the Morava's
      valley (1,2). Reservoirs of infection are infected humans and animals (dogs and
      rodents). Infection is transmitted by insects the most significant representative
      of which is a sandfly. The course of the disease may be acute, subacute and
      chronic and several forms are differentiated such as visceral, cutaneous and
      mucocutaneous. Signs of disease are elevated temperature, gastrointestinal
      disorders, splenomegaly and hepatomegaly and rarely generalized lymphadenomegaly.
      Laboratory findings point to pancytopenia. The diagnosis is established on the
      basis of parasitological findings in macrophages of the bone marrow and is
      confirmed by serologic tests (4,5). However, mortality is decreased to 5% after
      the application of 5-valent antimony and amphotericin B (6,7). CASE REPORT: A
      female patient aged 19 year from Novi Sad was admitted at the Clinic of
      Hematology due to unclear febrile state lasting 3 months accompanied by
      pancytopenia and enlarged spleen. The first discomforts were experienced in the
      second half of August in 1997 upon the patient's return from Sutomore. The
      disease started gradually with uncharacteristic manifestations. Firstly,
      discomforts developed in the region of the gastrointestinal tract and were
      characterized by loss of appetite, nausea, and vomiting in addition to drastic
      weight loss. Secondly, fatigue occurred during effort, later on at rest as well,
      accompanied by increased body temperature. Temperature increased twice a day and
      was followed by shuddering, fever, shivering and very often by nocturnal
      sweating. Antibiotics and antipyretics were used, but without fall of
      temperature. Subjective discomforts were increasingly pronounced, so that due to
      unclear febrile state and in addition to the present pancytopenia the patient was
      referred to hospital treatment and was therefore admitted at the Clinic of
      Hematology. Febrile state, tachycardia, a striking paleness of the skin and
      visible mucosa as well as splenomegaly were confirmed. Basic laboratory findings
      (Table 1) pointed to pancytopenia. Apart from anemia and mild thrombocytopenia,
      leukopenia with neutropenia, lymphocytosis and monocytosis were pronounced.
      Sternal puncture was the most significant diagnostic procedure on the basis of
      which the diagnosis was established. In hypocellular bone marrow in macrophages,
      both intra- and extracellular, protozoa were found in smaller and greater groups
      which resembled leishmaniasis (Figure 1). The diagnosis was confirmed by
      serologic tests to leishmaniasis, antibody titre was > 1:32. In order to exclude
      other infections and hematologic diseases, other diagnostic tests were performed
      (Table 1) and the findings were normal. After the establishment of diagnosis the
      patient was transferred to the Clinic of Infectious Diseases where the causal
      therapy with 5-valent antimony was introduced, parenterally. As early as the
      first week of therapy, the patient was afebrile, subjective discomforts
      disappeared, she regained appetite and put on weight. Also, the decrease of the
      spleen was observed as well as improvement in hematological findings. DISCUSSION
      AND CONCLUSION: This paper predominantly deals with hematological findings which
      are characteristic for leishmaniasis on the basis of which the diagnosis of this
      disease has been quickly established (1,2). Hematological findings were the key
      of diagnosis being confirmed by serologic and other tests. The disease is very
      rare in this region, so that there is a difficulty in recognizing it. In our
      case, the diagnosis was made on the basis of sternal puncture survey, because
      protozoa were found in hy

PMID- 10953561
TI  - [January 31--a day without cigarettes].

PMID- 10953560
TI  - [Facial nerve paralysis as a sequelae of chronic suppurative otitis].
AB  - INTRODUCTION: Facial palsy can be a consequence of untreated chronic suppurative
      otitis media. This disease can last for many years manifesting as partial
      deafness and ear effusion resulting in palsy after spreading of pathological
      process in the surrounding cranial structures. The patient with facial palsy
      cannot rise his forehead, nor close his eye on the involved side, while his cheek
      and lips just fall. MATERIAL AND METHODS: This retrospective research included
      patients operated for chronic suppurative otitis media with facial palsy during
      the last ten years. We have examined data on duration of disease, time of
      development of facial palsy and relations with other otogenic complications.
      RESULTS: We described 19 patients with this otogenic complication. Most of them-
      13 (68%) had symptoms of chronic suppurative otitis media for several years. In
      some cases, we found other otogenic complications, like acute mastoiditis in 4
      (21%), meningitis in 4 (21%), cerebral abscesses in 1 (5%) and cerebellar
      abscesses in 1 (5%). All patients were operated and the pathological process was
      completely removed. During operation we found polypoid formations in 9 (47%)
      patients, granulation tissue in 8 (42%) and cholesteatoma in 7 (37%) cases. In 16
      (84.2%) we did not find any visible defects on facial nerve canal, in 2 (10%)
      cases pathological process destroyed the canal in the tympanic region, and in 1
      (5%) facial nerve was partially bare in tympanic and mastoid region. 16 (84.2%)
      patients have fully recovered, in 2 (10%) cases sequelae remained and in 1 (5%)
      patient, who had meningitis and cerebral abscess, there were no signs of
      recovery. DISCUSSION: Facial paralysis as an otogenic complication, can originate
      from acute otitis media and secretory otitis media. The pathological process in
      chronic suppurative otitis media causes changes in mucous of middle ear,
      manifested by edema, submucous fibrosis and infiltration with chronic
      inflammation cells. Progressive spreading of these inflammation changes causes
      osteitis, which provokes invasion and bone destruction of inner ear, durae or
      facial canal and development of palsy. The sex of patients is not relevant. The
      significant data concern the duration of disease since 13 (68%) patients have
      suffered from chronic otitis for several years. This points out the silent
      character of the disease. The clinical picture of all patients with peripheral
      facial palsy is identical, no matter of etiology, so they are often wrongly
      classified and treated as Bell's palsy. That is the reason for imperative
      examination of middle ear in every patient with respective symptoms. Late and
      inadequate treatment is a common cause of further progressiveness of disease,
      which causes development of other otogenic complications that can jeopardize life
      of patient. Acute mastoiditis is the most frequently mentioned, but we also
      recorded the most severe complications as otogenic meningitis and cerebral and
      cerebellar abscesses. It is possible that bacterial toxins penetrate and provoke
      neuritis with bigger or smaller edema. On the other side, it is commonly
      considered that facial palsy appears with cholesteatoma of middle ear.
      Cholesteatoma directly distracts bones and provokes inflammation and also makes
      compression on nerve itself. Our research showed that there were no visible bone
      defects in most of the cases 16 (84%), but process developed through cracks, and
      only in 2 (10%) defect was in tympanic part of canal and in 1 (5.8%) facial nerve
      was bare in tympanic and partially in mastoid part two centimeters in length.
      Pathological process was operationally removed without opening the facial canal,
      because removal of the process provides decompression and relieve of nerve.
      Operation is followed by medicamentous treatment (antibiotics, corticosteroids).
      This treatment succeeded with full recovery in 16 (84.2%) patients, partial
      recovery in 2 (10%) and only one did not have any signs of recovery. CONCLUSION:
      Otogenic facial

PMID- 10953563
TI  - [Prognostic factors in gastric cancer. Our experience and review of the
      literature].
AB  - BACKGROUND: This review of the latest literature and retrospective analysis of
      the authors' series aimed to identify the most relevant prognostic factors for
      gastric cancer. METHODS: A total of 81 patients were operated in our series from
      1980 onwards. Eighteen patients underwent minor surgery and 5 were not treated.
      All resected patients underwent R2 lymphadenectomy. RESULTS: In the majority of
      cases the histiotype was found to be adenocarcinoma. Undifferentiated forms were
      only found in 8 cases. The prognostic factors identified in our series and in the
      most recent literature were age, lesion sites, histiotype, the number of
      metastatic lymph nodes and T3. The poor prognosis in younger patients may be
      explained by late diagnosis and more aggressive tumours. Neoplasms in the upper
      third of the stomach have a worse prognosis owing to a faster metastasis rate,
      lymphatic drainage directly into the left para-aortic lymph nodes and lack of
      serosa in the gastric fundus, meaning that in practice T2 becomes T3. Lymphatic
      diffusion represents one of the most important factors, in particular the number
      of lymph nodes affected by the tumour is decisive for prognosis: from the
      literature, in both T1-T2 and T3-T4, if > or = 5 lymph nodes are positive then
      survival rates decrease significantly. CONCLUSIONS: From our personal experience,
      N2 determines the prognosis in both T2 and T3. N2 is important, but survival
      diminishes in T3, thus demonstrating the importance of serous infiltration. The
      majority of Western and Japanese authors deem that T3 represents one of the
      decisive factors.

PMID- 10953562
TI  - [Quality control in surgery of locally advanced rectal cancer].
AB  - BACKGROUND: The role of surgery in the therapeutic balance of locally advanced
      rectal neoplasms needs to be redefined in the light of recent reports on the
      efficacy of radio- and chemotherapy in neoadjuvant treatment. METHODS: For this
      purpose, the authors analysed the results of 104 locally advanced rectal
      neoplasms during the decade 1987-1996 all of whom had undergone priority surgery
      (100% operability) using a decidedly radical approach. Of this continuous series,
      70 were T4 M0 (Group A) and 34 T4 M1 (Group B). Resectability in Group A was
      97.1% (87% R0 excisions) with sphincteric recovery in 72.8%. Resectability was
      73.5% in Group B (20% R0 excisions) with sphincteric recovery in 60%. RESULTS:
      Total operative mortality was 4.7% (2.9% for R0 operations, 10.2% for R2),
      morbidity was 24%. No survivor died during the follow-up: there were 6 local
      recidivations for 68 R0 operations (8.8%), half of which were only local. The
      mean survival for the entire series was 34 months: 4-5 months for R0 operations;
      for R1-R2 operations: 18 months for M0, 8 months for M1. None of the patients
      with local residual disease undergoing postoperative radiochemotherapy were
      recovered during surgery. CONCLUSIONS: A comparative evaluation of the results
      obtained with those reported in the literature involving single or multicentre
      series pretreated with radio- or chemotherapy is relatively difficult and non
      indicative owing to the numerous disparate aspects that have been the subject of
      debate and comment, ranging from the definition of locally advanced rectal cancer
      to the grounds for selecting patients and the comparative groups treated with out
      of-date surgical standards.

PMID- 10953564
TI  - [Cancer of the male breast].
AB  - BACKGROUND: Male breast cancer is a rare type of neoplasm, being 1% of all breast
      tumors. An increasing relevance is given to genetic factors. Familiarity is
      present in 10% of cases reported in literature. Gynecomastia is frequently
      associated. Personal experience about this pathology is compared with the most
      recent data of the literature. METHODS: Nine cases of male breast cancer observed
      among 519 breast tumors operated between 1982 and 1997 are reported. Etiologic
      and prognostic aspects, surgical and complementary therapy of breast cancer in
      man are examined and the high rate of II-III stage patients, mostly ER+ and PR+
      is underlined. Diagnosis is reached by ultrasonography and mammography, after an
      accurate clinical examination and confirmed by cytology after needle biopsy. The
      choice operation is total mastectomy with axillary lymphadenectomy according to
      Patey. RESULTS: According to our experience, 5 patients died for non neoplastic
      pathology, 1 patient lost at follow-up, 3 patients still alive after 66, 60 and
      12 months respectively. CONCLUSIONS: Male breast cancer is similar to the female
      one, but characterized by a higher hormone receptors positivity. Our survival
      data have no statistic significance. It is still discussed if prognostic
      difference between men and women is present or not.

PMID- 10953565
TI  - [Stricture plasty in Crohn's disease. Indications and results].
AB  - BACKGROUND: Aim of the paper is to evaluate the indications and results of
      stricture plasty in the treatment of intestinal obstruction due to Crohn's
      disease. It is hypothesized that, as far as fibrotic strictures are treated,
      operative morbidity will be reduced to a minimum. METHODS: Data regarding 147
      interventions for Crohn's disease performed in a 4.5 year-period have been
      prospectively collected. Eight interventions including stricture plasty have been
      identified and indication, morbidity and end results analyzed. RESULTS: In 8
      interventions 20 stricture plasties have been performed. As a rule, a stricture
      plasty is performed only when a resection would have sacrificed a too long bowel
      tract or it was inappropriate, in relation to stricture site. Three patients had
      fistulae, but those fistulae were not in the same site of stricture plasty and
      only one patient was malnourished and with active disease. There was no operative
      mortality or major morbidity, but there was only a short episode of hyperthermia.
      No relapses were observed after a 26-month mean follow-up. CONCLUSIONS: Stricture
      plasty is a useful tool in order to avoid extensive intestinal resections. If it
      is performed only on fibrotic strictures with inactive disease and only if a
      resection is deemed inappropriate, minimal morbidity and very good results can be
      anticipated.

PMID- 10953566
TI  - [Meckel's diverticulum. Our experience].
AB  - BACKGROUND: The paper aimed to highlight the percentage presence of Meckel's
      diverticulum compared to appendiceal pathology in a retrospective study and
      whether its surgical removal is always useful, even if asymptomatic. METHODS: The
      study was performed at the Institute of Emergency Surgery at the Second
      University of Naples (Head: Prof. R. Docimo) in 1211 patients affected by
      appendiceal-like pathology, reported to the authors' attention for both elective
      and emergency surgery from 1973 to today. The presence of Meckel's diverticulum
      was rarely diagnosed in preoperative patients; it was occasionally found in both
      elective surgery in patients with other abdominal pathologies, above all
      appendicitis, and in patients undergoing emergency surgery for acute pathologies
      (occlusion, peritonitis) caused by the former. The diverticulum was always
      totally removed (diverticulectomy or intestinal resection) even when it was
      asymptomatic. RESULTS: The results were satisfactory in all patients and at the
      one-year follow-up none complained of discomfort. CONCLUSIONS: We are convinced
      that Meckel's diverticulum should be investigated as a matter of course during
      appendectomy and, where present, it should be removed even if asymptomatic
      because the problems arising secondary to complications are undoubtedly more
      severe compared to any discomfort following its surgical removal.

PMID- 10953567
TI  - [Prevention of vaginal prolapse in patients undergoing abdominal hysterectomy].
AB  - BACKGROUND: In our study we evaluate a personally developed surgical technique
      that, when used for abdominal hysterectomy, helps prevent posthysterectomy
      vaginal wall prolapse. METHODS: We have used this modified surgical procedure in
      244 consecutive abdominal hysterectomies performed from January 1973 through
      December 1986, compared with 133 abdominal hysterectomies performed without this
      new procedure. Patients returned monthly and annually thereafter for follow-up.
      The longest follow-up period to date is 12 years. RESULTS: Of the 244 patients in
      our study followed up for 12 years, 234 (95.9%) retained excellent vaginal
      support. Vaginal wall prolapse occurred in 10 patients (4.1%), and it was
      asymptomatic prolapse, with the vaginal wall descending less than halfway from
      the ischial spines to the hymen. CONCLUSIONS: This procedure is an acceptable
      method to help prevent posthysterectomy vaginal wall prolapse.

PMID- 10953568
TI  - [Reconstructive surgery in oncological gynecology. Our experience].
AB  - BACKGROUND: Personal experience in reconstructive surgery for gynecologic
      oncology is reported. These techniques are playing, during last years, a leading
      role since it is necessary to assure a good treatment and top quality lifestyle
      to oncologic patients. METHODS: A retrospective study was made on 357 major
      surgical treatments for neoplastic disease at the IInd Clinic of Obstetrics and
      Gynecology, University of Bari. For each disease the technique, the length of
      surgery and possible complications have been reported. In total 50 reconstructive
      procedures on 357 surgical interventions for gynecologic neoplastic disease (14%)
      were made. RESULTS: There was no rate of mortality, and the complications were
      found only in 5 patients (10%). CONCLUSIONS: Reconstructive surgery can increase
      surgical radicality, improve the quality of life of the patients and reduce the
      postoperative complications.

PMID- 10953569
TI  - [Diagnosis and treatment of pheochromocytoma].
AB  - Early detection of a pheochromocytoma is necessary to avoid the cardiovascular
      complications of hypertension and to recognize the 10% of malignant neoplasms.
      Hypertensive changes, particularly hypertensive spikes and stable hypertension
      are the most common clinical features. A pheochromocytoma must be suspected in
      presence of various symptoms of which cephalea, tachycardia, diaphoresis are the
      most frequently encountered. Plasma catecholamines and 24-hours urine metabolites
      measurements have 60-100% and 72-99% sensitivity respectively. Radiologic
      procedures commonly used to locate a pheochromocytoma include CT and RM: they
      achieve 100% sensitivity for unilateral adrenal lesions and respectively 64% and
      88% sensitivity for extra-adrenal lesions. Scintigraphic localization with MIBG
      provides functional informations and is recommended for follow-up of the
      recurrent or metastatic pheochromocytoma. Preoperative medical treatment using
      alpha and beta blocking agents or calcium channel blockers has contributed to
      reduce perioperative morbidity and mortality. Anterior transabdominal approach is
      advocated as the standard operative procedure; this approach allows ready access
      to any site where tumors are obviously present and permits thorough exploration
      of the abdominal cavity for additional contralateral adrenal or extra-adrenal
      lesions. An accurate preoperative localization of a sporadic, unilateral, of less
      than 7-10 cm, benign neoplasm constitutes the indication for the laparoscopic
      adrenalectomy. Pheochromocytoma-free survival were 92% and 80% at 5 and 10 years
      respectively; in living patients without recurrence, hypertension-free survival
      was 74% and 45% at 5 and 10 years respectively. Extra-adrenal pheochromocytomas
      are frequently malignant (36%) and are associated with a high incidence of
      persistent or recurrent disease (32%).

PMID- 10953570
TI  - [Dislocation into the cardial lumen of a PTFE prosthesis used in the treatment of
      voluminous hiatal sliding hernia, A case report].
AB  - The authors report a case in which a PTFE prosthesis, used to treat a voluminous
      hiatal sliding hernia, dislocated inside the cardial lumen. Within two months the
      prosthesis had become decubitant and penetrated the cardial lumen, causing
      dysphagia, inappetence and weight loss. The use of radiological and tomographic
      imaging failed to provide a clear diagnosis; endoscopy alone was conclusive.
      Surgery was required to remove the prosthesis by resecting the distal esophagus
      and reconstructing the continuity of the digestive tract using terminolateral
      esophagogastric anastomosis (front wall of the stomach) in CEEA 21. The absence
      of a clear etiopathogenetic sequence of the migration of the prosthesis prompted
      the authors to stop using this type of surgery.

PMID- 10953571
TI  - [Gastrointestinal stromal tumors. A case of small intestine stromal tumor (SIST)
      with an uncertain biological aspect].
AB  - Tumors of the small intestine are relatively rare. The diagnosis is difficult to
      establish because the symptoms are vague and non-specific. Although the small
      intestine constitutes 75% of the length and over 90% of the mucosal surface area
      of the gastrointestinal tract, only 1 to 2% of gastrointestinal malignancies
      occur in this segment. Metastases are usually present at the time of diagnosis.
      The outcome of these patients can be improved if the possibility of a malignant
      small bowel tumor is considered in all cases of unexplained abdominal pain or
      gastrointestinal bleeding, especially in younger age. Malignant tumors occur with
      increasing frequency in distal small bowel with a preponderance of malignant
      lesions in the ileum compared with the jejunum and the duodenum. Adenocarcinoma
      is the most common tumor of the primary malignant small bowel tumors, followed by
      carcinoid, lymphoma and leiomyosarcoma. Mesenchymal tumors of the
      gastrointestinal tract, traditionally regarded as smooth muscle tumors, have
      demonstrated different cellular differentiations based on immunohistochemical and
      ultrastructural features. Therefore the terms leiomyoma and leiomyosarcoma have
      been replaced by a more encompassing term, gastrointestinal stromal tumor (GIST).
      The majority of GISTs occurs in the stomach; stromal tumors involving the small
      intestine (SISTs) are far less common but seem to have greater malignant
      potential. The clinical a case of a small intestinal stromal tumor (SIST),
      localised in the jejunum and characterised by an uncertain histological aspect,
      is presented and a review of the literature is made.

PMID- 10953572
TI  - [Congenital lobar emphysema in adults].
AB  - Due to the severity of respiratory symptoms, congenital lobar emphysema often
      requires surgical treatment in the early stages of life. Diagnosis of congenital
      lobar emphysema in adult life is therefore unusual, often presenting with mild
      symptoms. Diagnostic assessment is therefore of great importance in the treatment
      of these patients. A case of congenital lobar emphysema in an adult is reported
      and the diagnostic and therapeutical approach are discussed. The use of new
      diagnostic techniques such as dynamic RMN and SPET V/Q lung scan may improve the
      accuracy of the diagnostic evaluation. Pulmonary lobectomy led to marked
      improvement in respiratory function. Accurate diagnosis and appropriate
      management of congenital lobar emphysema in adult patients can lead to favourable
      results.

PMID- 10953573
TI  - [Pulmonary metastasis of malignant peritoneal mesothelioma. Review of the
      literature and a case report].
AB  - The authors describe the clinical case of a 54 year old patient, affected by
      malignant peritoneal mesothelioma treated by chemotherapy, who subsequently
      developed a lung lesion, treated by surgical wedge resection. The histologic
      examination of the surgical specimen, which led to the diagnosis of an
      intraparenchymal necrotic focus, confirms the favourable result of the adjuvant
      therapy. A review of the literature showing the rarity of lung metastases from
      malignant peritoneal mesothelioma is presented.

PMID- 10953574
TI  - [Neuronal dysplasia of the colon. A case report].
AB  - A clinical case of Neuronal Intestinal Dysplasia (NID) is reported. This is an
      important pathology which is part of congenital alterations of bowel's
      innervation. This disease consists of two forms (A and B) which occur during
      different ages causing problems in intestinal motility with consequent various
      symptoms. Actually NID is diagnosed easier than in the past because
      histopathological techniques are very refined and permit to distinguish NID from
      cases once classified as Hirschsprung's disease. Histology can show an increase
      of Ach and Ldh activity in cholinergic fibers of lamina propria and of circular
      layer of intestinal wall. In this report a chronic status of constipation
      refractory to medical therapy has been treated with a total colectomy and an ileo
      rectal anastomosis, resulting in a complete resolution of symptoms.

PMID- 10953575
TI  - [Migration of the catheter of a totally implantable venous system. A rare
      mechanical complication].
AB  - Catheter migration, represents a rare, mechanical complication following the use
      of totally implantable venous devices. A case, in which the catheter was inserted
      into the right internal jugular vein by percutaneous route, without radiological
      control, is described. Following the chemotherapy infusion drugs, the patient
      developed a catheter displacement and subcutaneous extravasation. Etiological
      hypotheses and modalities of prevention are discussed.

PMID- 10953576
TI  - [Our choice of the method to induce pneumoperitoneum in videolaparoscopic
      surgery].
AB  - BACKGROUND: In laparoscopic surgery, pneumoperitoneum may be obtained either by a
      blind or an open access technique. These two techniques and the advantages of
      Hasson technique are compared. METHODS: Through January 1998 and May 1999, 262
      unselected patients underwent laparoscopic surgery; pneumoperitoneum was obtained
      with a random technique, while in the patients previously operated on the open
      technique was always performed. In 161 cases (61.5%) pneumoperitoneum was
      obtained with Hasson technique and in 101 (38.5%) with Veress technique. All the
      patients were clinically evaluated after surgery and then after 30-40 days. The
      complications encountered were always associated with the Veress needle blind
      access: peritoneal space insufflation in 3 cases, greater omentum insufflation in
      3 cases, 4 cases of difficult management and only one case of incisional hernia
      on the umbilical wound. RESULTS: Our data confirm that Hasson open technique is
      safer than Veress blind technique as the risk of severe early and late
      complications is lower. CONCLUSIONS: The open laparoscopic technique with the
      Hasson trocar is recommended as it showed to be a quicker, safer and superior
      technique for obtaining pneumoperitoneum.

PMID- 10953577
TI  - [Complete section of the main bile duct during laparoscopic cholecystectomy.
      Surgical treatment].
AB  - Three cases of biliary tract serious lesions during videolaparoscopic
      cholecystectomy are reported. They were executed in other hospitals and presented
      big technical restoring difficulties, not easily resolvable. In 2 cases of
      lithiasic cholecystitis there was a complete damage of common biliary duct, in
      the third one there was a double main biliary duct binding with removal of a
      biliary tract segment. In all cases a biliary confluence-jejunal anastomosis with
      Roux en y loop was made up. In all cases the operation was difficult because of
      main bile duct fragility and modest expansion. In the third one the presence of a
      secondary biliary duct in gallbladder fossa not recognized but drained outside
      with a common drainage placed during the operation has prevented appearance of
      jaundice with dilatation of biliary ducts. It has heavily conditioned confluence
      jejunal anastomosis with Roux en Y loop. In all cases tubes were left in the
      biliary duct for few months in order to calibrate it. In 2 patients postoperative
      course was characterized by the appearance of an external biliary fistula which
      has spontaneously disappeared. One year later both patients don't present any
      stenosis or cholangitis problem.

PMID- 10953578
TI  - [Hemorrhoidectomy with ropivacaine (Naropin) local anesthesia. Preliminary
      experience].
AB  - BACKGROUND: The use of local anesthesia in non-septic anal surgery is now well
      established. Tolerance to local injection, duration of local effect and the risk
      of local or systemic complications still represent unsolved issues. Ropivacaine,
      a new local anesthetic, seems particularly indicated for this kind of surgery
      because of its pharmacologic properties which reduce patient's discomfort during
      infiltration and provide good antalgic coverage in the first hours following the
      operation. METHODS: The first 20 consecutive cases operated with local anesthesia
      by ropivacaine have been prospectively studied. All patients have been given an
      11-point box VAS scale which is used for subjective evaluation of pain. RESULTS:
      Mean pain score resulted 1.1, 1.6 and 1.4 at 1, 2 and 3 postoperative hours,
      respectively. Thirty percent of patients subsequently required pain medication up
      to the first bowel movement. No complications related to the use of ropivacaine
      has been observed. CONCLUSIONS: This new drug can be safely used in the
      outpatient or Day-Surgery treatment of hemorrhoids.

PMID- 10953579
TI  - [Immunology: experimental science or clinical service?].

PMID- 10953580
TI  - [Home hospitalization].

PMID- 10953581
TI  - [Postsurgical meningitis caused by Pseudomonas aeruginosa: study of 15 cases and
      review of the literature].
AB  - OBJECTIVE: Pseudomonas aeruginosa meningitis is a rare condition which is usually
      associated with pathology in the ORL field, neurosurgery or local neurologic
      manipulations. The characteristics, epidemiology, and course of this entity were
      determined. METHODS: Fifteen episodes of nosocomial postsurgical Pseudomonas
      aeruginosa meningitis occurred between 1989 and 1996 were retrospectively
      analyzed. RESULTS: A previous cranioencephalic trauma was recorded in 46.6% of
      patients. The portals of entry included: intraventricular catheter (IC) (12
      cases), CSF fistula (2 cases), and craniotomy (1 case). In five occasions (41.6%)
      the microorganism was also recovered from the intraventricular catheter. Once
      culture results were available, therapy with active drugs against Pseudomonas was
      instituted and in 7 occasions was accompanied by the removal of IC. Eight
      patients eventually cured and two patients relapsed. The absence of cure was
      significantly associated with non-removal of the IC (p < 0.01). The infection
      resulted in death in 26.6% of patients. CONCLUSIONS: Postsurgical Pseudomonas
      aeruginosa meningitis is an entity of growing relevance. It is associated with
      relevant morbi-mortality. Catheter removal is essential to obtain a favorable
      outcome.

PMID- 10953582
TI  - [Clinical and analytical findings in patients with toxic oil syndrome. Study of a
      cohort of 758 patients].
AB  - OBJECTIVE: To report the symptoms and analytical findings observed in the
      collective of patients affected with the toxic oil syndrome (TOS) 18 years after
      the poisoning. METHODS: At the Centro de Investigacion sobre el Sindrome del
      Aceite Toxico (CISAT) we followed the clinical and analytical course of 758
      patients affected with the TOS since December 1997 up to May 1999. Patients were
      evaluated by means of a previously standardized questionnaire in which a clinical
      review and a battery of complementary tests (thyroid hormones, spirometry with
      diffusion test and arterial gasometry) were included. One hundred and sixty-two
      patients underwent also echocardiogram because of presumptive pulmonary
      hypertension and/or heart disease. RESULTS: Out of the 758 patients, 516 were
      females and 242 males (M:F ratio 2:1), with ages ranging from 17 to 84 years
      (mean age 47 years). One of the most remarkable findings was the increased
      prevalence of cardiovascular risk factors: arterial hypertension (34%),
      dyslipemias (44%), overweight (40%), obesity (27%), carbohydrate intolerance (9%)
      and diabetes mellitus (9.4%). The most common reported symptoms were: cramps
      (78%), arthralgias (78%), and paresthesias (70%). Only 2.8% of patients reported
      to be asymptomatic. The analytical results most commonly changed were: changes in
      lipidic and carbohydrate metabolism (already reported), overt or subclinical
      hypothyroidism (6.6%) and respiratory changes in patients with no previous
      pulmonary disease: changes in spirometry (6%), diffusion test (8%) and hypoxemia
      (18%). Echocardiographic findings suggestive of PHT were obtained in 3.1% of
      cases. CONCLUSIONS: Although TOS occurred in 1981, this syndrome still has a
      relevant morbidity in a portion of the spanish population. To remark the high
      prevalence of cardiovascular risk factors with changes in lipidic and
      carbohydrate metabolism and subclinical hypothyroidism observed in our series.
      Further studies are necessary to evaluate the actual dimension of this poisoning.

PMID- 10953583
TI  - [Effect of home hospitalization in the reduction of traditional hospitalization
      and frequency of emergencies in heart failure].
AB  - OBJECTIVE: Medical care to patients with heart failure (HF) entails high needs in
      health care and social resources. Hospital at home (HH) is a potentially useful
      care alternative for these patients. MATERIALS AND METHODS: Observational study
      with 110 elderly patients with non complicated HF admitted to an HH unit.
      Patients were treated with educational support (clinical, dietetic and
      pharmacologic) and intensive home follow-up. Conventional hospital admissions and
      visits to the Emergency Department were analyzed during the 90 days before and
      after HH. RESULTS: After HH, conventional hospital admissions decreased by 86%
      and visits to the Emergency Department by 91%. The mean Barthel Index changed
      from 74 to 77 (p < 0.05, in all cases). Ninety-six percent of patients were
      satisfied or very satisfied with HH. CONCLUSIONS: In elderly patients with non
      complicated HF, the intervention of an HH unit reduces conventional hospital
      admissions and the number of visits to the Emergency Department, the personal
      satisfaction degree is high and the functional capacity does not worsen.

PMID- 10953584
TI  - [Bacteremia caused by Stenotrophomonas maltophilia: epidemiology, clinical
      features, and prognosis factors].
AB  - The epidemiologic, clinical and prognostic characteristics of Stenotrophomonas
      maltophilia bacteremias for a six-year period (January 1993 to December 1998)
      were reviewed. Twenty episodes of S. maltophilia bacteremia were include, which
      represented 0.62% of all bacteremias caused by gram-negative rods during that
      period. Seventy percent of bacteremias were clinically significant. The most
      common predisposing factors were the previous use of antimicrobial agents and the
      presence of vascular catheters. In most cases (57%), the origin of bacteremia was
      the intravascular catheter. The course of patients was favorable and all patients
      cured.

PMID- 10953585
TI  - [Immunotherapy prospects in tuberculosis: cytokines and DNA "vaccines"].

PMID- 10953586
TI  - [Value of prostatic specific antigen screening in prostatic cancer].

PMID- 10953587
TI  - [Diagnosis of alcohol consumption: first of all, primary care].

PMID- 10953588
TI  - [Bisphosphonates in the treatment of osteoporosis].

PMID- 10953589
TI  - [Criteria for the use of antithyroid agents in the treatment of
      hyperparathyroidism].

PMID- 10953590
TI  - [Palmoplantar exanthema in patient with HIV infection, parenteral drug user, and
      sexually promiscuous].

PMID- 10953591
TI  - [Hydropneumothorax].

PMID- 10953592
TI  - [Fever and bilateral suprarenal mass].

PMID- 10953593
TI  - [A 68-year-old male with prolonged fever, disorientation, and convulsions].

PMID- 10953594
TI  - [Migratory serpiginous eruption].

PMID- 10953596
TI  - [Thymus carcinoma associated with myasthenia gravis].

PMID- 10953595
TI  - [Survival in a case of ethylene glycol poisoning with extreme acidemia].

PMID- 10953597
TI  - [Thrombopenia and Raynaud's phenomenon as initial manifestations in a patient
      with positive anti-Ro/SS-A antibody and salivary gland biopsy compatible with
      Sjogren's syndrome].

PMID- 10953598
TI  - [Hypersensitivity syndrome caused by anticonvulsants].

PMID- 10953599
TI  - [Mycobacterium xenopi pulmonary infection after starting high efficiency
      treatment with indinavir].

PMID- 10953600
TI  - [Partial splenectomy or "the half-empty spleen"].

PMID- 10953601
TI  - [An original accent in the concert of ideas...].

PMID- 10953602
TI  - [Homocysteine and atherosclerosis. The controlled clinical trials phase that
      people have been waiting for so long. Can multivitamins reduce coronary
      disease?].

PMID- 10953603
TI  - [Sex and proliferation or the cell cycle in the pathogenesis of lupus
      erythematosus].

PMID- 10953604
TI  - [Effectiveness of partial splenectomy in the treatment of hereditary
      spherocytosis].
AB  - OBJECTIVES: To evaluate the hematological and clinical response to partial
      splenectomy in a group of children with hereditary spherocytosis. MATERIAL AND
      METHODS: We analyzed the main hematological and clinical features in 13 patients
      with hereditary spherocytosis submitted to partial splenectomy. The diagnosis of
      the disease and the hematological studies was made according to standard methods.
      To establish the inheritance pattern we also studied both parents. During the
      surgical procedure the upper two thirds of the spleen were removed and the lower
      pole was preserved. We use prophylactic penicillin (250 mg twice a day) during 3
      years. RESULTS: The diagnosis of the disease was made during the first year of
      life in 11 patients, 76.9% had neonatal hyperbilirrubinemia, 53.8% showed
      hepatomegaly and in 69.2% we observed splenomegaly. 84.6% received blood
      transfusion. The hemoglobin level was significantly increased (p = 0.04) and the
      reticulocytes significantly diminished (p = 0.01) after splenectomy. No hemolytic
      crises, blood cell transfusion requirement neither infection was observed after
      surgery. CONCLUSIONS: Although the number of patients and the post-surgical
      follow-up is reduced, the hematological recovery observed in our cases suggest
      that partial splenectomy is a beneficial surgical procedure for the treatment of
      the typical and severe form of hereditary spherocytosis.

PMID- 10953605
TI  - [Hematopoietic cell transplantation. Experience at the Western National Medical
      Center].
AB  - Bone marrow transplantation has recently reached an special place as a
      therapeutic tool, which was not available ten years ago. AIM AND SETTING:
      Descriptive information about the first fifteen cases transplanted at Centro
      Medico Nacional de Occidente, on a third level attention in Guadalajara, Jalisco,
      Mexico. MATERIAL AND METHODS: Fifteen patients were transplanted, were carried
      out autologous transplantation in ten patients and five have received allogeneic
      transplant; one allogeneic transplant was performed with bone marrow aspiration
      donor, all next donation were taken off from peripheral blood stem cell through
      apheresis procedures. From autologous transplant 3 with chronic myelogenous
      leukemia (CML), 3 with Hodgkin's disease, 2 with solid tumor, 1 with high risk
      acute myelogenous leukemia and 1 large and small cell lymphoma III-B stage.
      Received allogeneic transplant 4 patients with CML in chronic phase and one with
      acute lymphoblastic leukemia Ph+. RESULTS: All patients grafted, the median time
      to achieve > 0.5 x 10(9)/L granulocytes was 14 days (range: 11-18) from
      autologous and 16 (range: 14-18) days from allogeneic transplant, whereas the
      median time to achieve > 20 x 10(9)/L platelets was 18 days (range: 15-35) from
      autologous and 22 days from allogeneic, three patients died into 100 days
      postprocedure, two allogeneic, from graft versus host disease III-IV degree, and
      one autologous from interstitial pneumonia, surviving patients have showed +30
      days to +1000 days survival. CONCLUSION: With these data we show that this
      procedure is inexpensive, is factible and possible if it does coexist with
      multidisciplinary and on time support, interest, dedication on care, and enough
      information and desire to do it, including official decisions to perform and
      sponsor its continuity to the people who participate in it.

PMID- 10953606
TI  - Perceived psychological stress in diabetes mellitus type 2.
AB  - We studied the factors associated with perceived psychosocial stress in patients
      with diabetes mellitus type 2. A cross-sectional study was carried out in 105
      patients (27 men and 78 women) with a mean age of 51.6 (50.2-52.5, 95% CI) years
      and 8.6 (7.3-9.8, 95% CI) years since diagnosis. The patients were overweight
      with body mass index (BMI) of 27.6, and most of them had deficient metabolic
      control (mean glucose of 10.6 nmol/L and HbA1c of 9.2%). Glycated hemoglobin was
      associated with BMI (negatively, p = 0.002), with adherence to diet (negatively,
      p = 0.027) and with years since diagnosis (p = 0.031). The association with BMI
      was found only in women. It was explained by the fact that obese women had fewer
      years since diagnosis, and recently diagnosed patients have a better metabolic
      control. A stepwise multiple regression analysis showed perceived stress
      associated with percent body fat and blood glucose in the total group, with years
      since diagnosis in women (p = 0.02), and with BMI in men (p = 0.03). No
      association was found between perceived stress and adherence to treatment. We
      concluded that in our group, perceived stress was associated with obesity and
      metabolic control.

PMID- 10953607
TI  - [Hepatitis C viral in patients with terminal chronic kidney failure. I.
      Prevalence].
AB  - BACKGROUND: The prevalence of hepatitis C in patients with end stage renal
      disease, under renal replacement therapy either with hemodialysis (HD) or
      continuous ambulatory peritoneal dialysis (CAPD), is higher than in the general
      population. The prevalence of hepatitis C in patients under dialysis, however, is
      unknown in Mexico. Thus, the major goals of the present study were to determine
      the prevalence of hepatitis C in our patients on dialysis, and the risk factors
      associated with it. METHODS: We performed a cross-sectional and comparative study
      in patients under dialysis in three hospital centers in the south of Mexico City.
      For every patient we evaluated: age, gender, etiology of the renal failure,
      modality and time in dialysis, transfusion and surgical history, serum albumin,
      aminotranferases, BUN, and serum creatinine. The presence of hepatitis C was
      assessed by ELISA II and qualitative RT-PCR in blood samples. In all patients
      diagnosed as having hepatitis C, RT-PCR to amplified part of the virus genome was
      also carried out in the dialysis fluid. RESULTS: We studied 235 dialysis patients
      that were classified according to their dialysis modality in: 132 patients under
      CAPD, 17 under CAPD and history of HD (PD/HD) and 86 under HD. The time under
      dialysis was different between the study groups: CAPD 29.6 +/- 22.3 months, PD/HD
      39 +/- 42.3 and HD 14.2 +/- 15.6 (p < 0.01). The presence of hepatitis C was
      detected in 24 of the 235 patients, for a global prevalence of 10.2%. In no case
      was viral RNA found in the dialysis fluid. The prevalence varied, however,
      according to the type of dialysis. It was in the CAPD group 4.5%, 12.7% in the HD
      group, and 41.1% in the PD/HD group (p < 0.001). The multivariate analysis showed
      that the risk factors for hepatitis C are transfusions before the year of 1991
      (Odds Ratio = 6.4), and history of hepatitis (OR = 4.3). Since less patients are
      seen with transfusions before 1991, we constructed another model in which this
      variable was excluded. This new multivariate model showed that history of surgery
      (OR = 4.4), the use of HD as the dialysis modality (OR = 3.5), and prolonged time
      under dialysis (OR = 1.01) were all significantly associated with the presence of
      hepatitis. DISCUSSION: Our results show that the prevalence of hepatitis C is
      lower in our patients that the prevalence reported by many others (average of
      other countries 18.5%). Since we found a higher prevalence in HD than in CAPD,
      even with the lower time under dialysis in the HD group, it is possible that our
      lower overall prevalence is secondary to the fact that CAPD is the most frequent
      mode of dialysis in our country. We observed the highest prevalence in the PD/HD
      group, that is probably due to longer exposure to the risk factors. The
      association with transfusions before 1991 indicates that the infection was
      acquired in some patients before dialysis was started. Our results showed that
      the CAPD is the dialysis technique with lower risk of hepatitis C infection.

PMID- 10953608
TI  - [Genetic differentiation with restriction patterns between pathogenic and non
      pathogenic monoxenic Entamoeba histolytica].
AB  - Cysteine-proteinase of Entamoeba histolytica have been considered implicated like
      important virulence factors in the pathogenesis of amebiasis. On the basis of the
      differences in ethnic gene that encodes to 30 kDa proteinase. The present study
      validated a strategy to differentiate strains of pathogenic and non-pathogenic
      Entamoeba histolytica by restriction patterns. MATERIALS AND METHODS: Thirteen
      stool samples with Entamoeba histolytica cyst from 4 asymptomatic and 9
      symptomatic patients ages and sex different into Robinson' medium were used. DNA
      obtained was used by amplified gene ethnic and it was cut with restriction enzyme
      Taq I and Hinf I. RESULTS: All strains were cultivated into Robinson's medium. A
      530 bp fragment which hybridated with probe for Entamoeba histolytica was
      obtained. By the way valuation by restriction patterns with Taq I and Hinf I show
      that two of four samples of asymptomatic patients belong to pathogenic strain. It
      agrees with control strain positive HM-1:IMSS. Last 9 belonged to symptomatic
      patients with pathogenic strain. CONCLUSIONS: These results indicate that ethnic
      amplified by polymerase chain reaction is insufficiently to establish
      differential diagnostic. Therefore is necessary carry out enzyme digestion to
      identify pathogenic strain.

PMID- 10953609
TI  - Satisfaction related factors of attendants to a medical research meeting.
AB  - OBJECTIVE: To assess satisfaction of attendants to a National Meeting on Medical
      Research in relation with the scientific quality and level of discussion of the
      research work. MATERIAL AND METHODS: An anonymous self-applied questionnaire was
      handed out to gather opinions about the scientific quality, level of discussion
      of the research work, and overall satisfaction with the meeting. The studied
      population included 400 physicians, all of them authors or collaborators of the
      research work presented. RESULTS: The rate of response was 62% (n = 249). Two
      hundred and twenty-four approved the scientific quality (90%), and 203 were
      satisfied with the level of discussion of research (88%); 239 were satisfied with
      the meeting as a whole (96%). The factors associated with dissatisfaction
      regarding the quality of the scientific meeting were the masculine gender (OR =
      2.7, CI 95% = 0.8-9.l, p = 0.06), having an M.Sc. or Ph.D. degree (OR = 2.3, CI
      95% = 0.9-5.5, p = 0.03), and having attending prior meetings more than twice (OR
      = 5.0, CI 95% = 1.5-18.4, p = 0.001). CONCLUSIONS: Most of the attendants were
      satisfied with the scientific quality and discussions of the research work. The
      masculine gender, having an M.Sc. or Ph.D. degree, and prior assistance were the
      factors associated with dissatisfaction of the scientific quality of the Meeting.

PMID- 10953610
TI  - GST-pi expression in BCR-ABL+ and BCR-ABL- cells from CML patients.
AB  - Our laboratory has been involved in the study of glutathione-sulfhydryl
      transferase-pi (GST-pi) for several years. We have recently observed that during
      haematopoiesis in BMSC liquid cultures from CML patients who were candidates for
      transplant GST-pi was expressed in presumably malignant cells during different
      stages of cellular maturation. To confirm this finding, in the present work we
      are detecting GST-pi expression by immunofluorescence in BCR-ABL+ and BCR-ABL-
      cells done by FISH of PB from 30 CML patients during different clinical status:
      treatment (T), hematological relapse (R), blastic crisis (BC) or post
      allotrasplant (PT). As well as in PB from 30 Blood-Bank donors. The results were
      %BCR-ABL+ GST-pi+ cells: T = 1-67, R = 33-69, BC = 90-100 and PT = 1-2; %BCR-ABL-
      GST-pi+ cells: T = 2-31, R = 5-18, BC = 0-10 and PT = 2-5; %BCR-ABL- GST-pi-
      cells: T = 2-97, R = 13-62, BC = 0 and PT = 93-96; %BCR-ABL+ GST-pi- cells: T =
      0, R = 0, BC = 0 and PT = 0. GST-pi was not expressed in donor cells. The results
      obtained confirm our previous observations and suggest that GST-pi expression
      might be used for the evaluation of the minimal residual disease in CML patients.

PMID- 10953611
TI  - [Current management of drug addiction].
AB  - Alcohol abuse is an endemic problem in the country, by itself is responsible of
      9% of the global burden of disease due to premature death and disability
      associated with cirrhosis, accidents, homicides and dependence. Use of other
      drugs is increasing with an important participation of cocaine and with out
      breaks of heroin use in the northern border. With the increase of drugs with
      higher potential of development of addiction, new are required to treat
      dependence and sequels derived from chronic use. The aim of this paper is to
      provide an overview of the available alternatives to be instrumented within the
      health system.

PMID- 10953612
TI  - [Genetic determinant factors of resistance to HIV infection and of control of
      progression to AIDS: implications on pathogenesis and therapeutic approaches for
      the eradication of HIV. A review].
AB  - In this review, we describe and discuss the genetic factors that, up to some
      point, determine resistance to the infection and control the progression of the
      disease in HIV-infected individuals. Genetic factors may account for non
      progression or slow progression of the disease in some of so called long-term non
      progressors HIV-infected individuals. In general, this group shows no symptoms
      for more than 10 years, while their circulating T CD4+ cells levels remain stable
      and they usually have a low virus load. Even though non-progression and rapid
      progression phenomenon are still not fully understood, there probability exists
      that some class I and class II MHC alleles are associated with a greater or
      smaller risk to develop AIDS. Class I HLA-B*35 and Cw*04 alleles are the ones
      commonly associated with the rapid transition of the infection into AIDS. In
      contrast, heterozygosity for class I HLA alleles and, particularly, the absence
      of HLA-B*35 and Cw*04 may contribute to non-progression. Studies which set
      forward other HLA alleles as possibly taking part of the pathogenic mechanism of
      non-progression are also described; although, relevant methodological problems
      can be noticed. Furthermore, this review explains and discusses allelic
      variations for some of the components of the chemokine receptors family,
      particularly the genes which codify for CCR5 and CCR2 and other genetic factors
      such as the SDF1-3'. A variant of the alpha SDF1 chemokine gene that have been
      associated with AIDS' slow progression or non-progression in HIV-infected
      individuals. As a whole, the factors described in this review are those that
      influence the natural history of the disease due to HIV and give an example of
      what genetic or multigenetic influence can have over the pattern of evolution of
      HIV infection. Finally, we mention the possible implications that the
      identification of the genetic markers has in the pathogenesis of HIV disease and
      in the development of the new therapeutic strategies to control or eliminate HIV.

PMID- 10953613
TI  - [Genetics of type 2 diabetes mellitus: genes implicated in early onset diabetes].
AB  - Non-insulin dependent type 2 diabetes (NIDDM) is a chronic and degenerative
      disease characterized by elevated glucose serum and the predisposition to the
      development of vascular complications. In Mexico the incidence of the disease
      reaches 8%, where one in every ten patients are diagnosed before age 40 (early
      onset diabetes). NIDDM is a clinically and genetic heterogeneous entity.
      Mutations in the glucokinase gene and the genes for the transcription factors HNF
      1 alpha, HNF-4 alpha, IPF-1, HNF-1 beta y HNF-3 beta have been demonstrated to
      cause MODY, a subtype of NIDDM characterized by autosomal dominate pattern of
      inheritance and an early-onset. Mutations in any of these genes result in
      deficient insulin synthesis and/or secretion. Five of these genes encode
      transcription factors that activate the transcription of various genes in
      pancreatic beta cell including, the insulin gene. Mutations in any of the genes
      associated to MODY may contribute to the insulin secretion deficiency frequently
      observed in early-onset type 2 diabetic patients. The structural and functional
      analysis of these genes, as well as other transcription factors expressed in
      pancreatic beta cell has allowed their recognition as putative candidate genes
      involved in the susceptibility to develop the disease.

PMID- 10953614
TI  - [Physiopathology of nephropathy studied with contrast media].
AB  - For the technological advances in diagnostic and therapeutic procedures, the use
      of intravenous contrast media in the hospital is more and more frequent. It can
      produce acute renal failure secondary to its nephrotoxicity known as contrast
      media nephropathy. This review describes the pathophysiologic mechanisms of
      contrast media injury, including cytotoxicity caused by hyperosmoloarity of
      contrast media, the hemodynamic factors and the role of the renin-angiotensin
      system, prostaglandins, oxygen free radicals, endothelin-1, adenosine, nitric
      oxide and others. The understanding of this information is of vital importance
      for the development of prophylactic strategies for contrast media nephropathy.

PMID- 10953615
TI  - [Role of the allelic E4 variant of apolipoprotein E in lipid concentrations in a
      Mexican rural indigenous population predisposed to type 2 diabetes mellitus].

PMID- 10953616
TI  - [Ethical considerations on human cloning. A psychoanalytic perspective].
AB  - A brief review of ethical issues related to two types of human cloning is
      presented: cloning embryonic cells not intended to culminate in the birth of a
      new individual and cloning human beings. Advantages and objections related to
      both types of human cloning are analyzed from an ethical point of view.
      Repercussions on individuals born by the technique of cloning are discussed from
      a psychoanalytical perspective. It can be concluded that cloning embryonic cells
      could be admissible, while not cloning considered as a reproductive option.

PMID- 10953617
TI  - [Validation of the use of an ELISA test in the detection of Chlamydia pneumoniae
      antibodies].

PMID- 10953619
TI  - [Nutritional treatment in the prevention of complications of type 2 diabetes
      mellitus].

PMID- 10953618
TI  - [Scrutiny, diagnosis, initial evaluation, and follow-up of the patient with type
      2 diabetes].

PMID- 10953620
TI  - [Diabetic nephropathy].

PMID- 10953621
TI  - [Prevention and treatment of diabetic foot].

PMID- 10953622
TI  - [Assessment of macrovascular complications in type 2 diabetes mellitus].

PMID- 10953623
TI  - [Other complications of diabetes].

PMID- 10953624
TI  - Determination of copper, selenium and zinc in human blood by inductively coupled
      mass spectrometry: the sources of uncertainty and variability of results.
AB  - The concentration of Cu, Se and Zn in whole human blood and plasma was analysed
      by inductively coupled plasma mass spectrometry. Method involved dilution of
      sample by diluted nitric acid and Triton X-100 and measurement of 65Cu, 77Se and
      66Zn intensities. Calibration solutions were spiked by main interferents. In
      order to evaluate suitability of the method for recognition of alternation of
      trace elements concentration, the uncertainty of results was estimated. The major
      part of uncertainty was due to repeatability, the other source (calibration and
      interferences) were found to be of lesser importance. The resulting uncertainty
      of concentration of mentioned trace elements is low as compared to between
      individual variability. Short-term (within day) and long-term (between day)
      variability of trace elements concentration was investigated and compared with
      between individual variability too. The time variability was negligible except
      for Zn concentration. The alternations of trace elements concentration in
      patients with several renal diseases were investigated. Only in case of patients
      in end-stage renal disease: hemodialyzed patients and patient treated by
      continuous ambulatory peritoneal dialysis the significant alternations were
      proved.

PMID- 10953625
TI  - Dehydrogenase activity in the blood and brain after adaptation to intermittent
      hypoxia.
AB  - Activities of LDH (lactate dehydrogenase) and alpha-HBDH (alpha-hydroxybutyric
      dehydrogenase) were measured in rats after intermittent exposure to the aerogenic
      hypoxia at a simulated altitude of 7000 m during the postnatal period (since
      birth to the 18th day) or in adulthood (older than the 90th day), except days 6,
      7, 13, and 14 of the experiment. Enzymatic activity was measured using standard
      test kit (Biochemical Test Combination, Boehringer). Twenty hours after the last
      exposure to hypoxia, the activity of both enzymes was elevated in the serum and
      in the brain of the young rats. In contrast, in adult rats, the exposure to
      hypoxia did not result in changes of the enzyme activity in the serum or in the
      brain. Our results indicate that, whereas in adults the biochemical adaptation to
      repeated aerogenic hypoxia has no effects on the enzymatic activities of
      dehydrogenases, the same stimulus during the early postnatal period brings about
      rising of the aerobic glycolysis contribution to the total energy balance. Such
      increase is enabled by the increase of LDH and alpha-HBDH activities.

PMID- 10953627
TI  - [Unveiling of the sculpture, Thysia by Olbram Zoubek,in memory of the deceased
      who donated their bodies for the education of medical students in anatomy].

PMID- 10953626
TI  - [Hormonal profile in men with premature androgenic alopecia].
AB  - Androgenetic alopecia especially that with premature onset can be a cause of
      serious psychic trauma. As far as the treatment with antiandrogens, inhibitors of
      5 alpha-reductase or hair transplantation represents a heavy economic burden for
      the patient, we tried to exclude other hormonal causes or to find a criterion for
      the apt candidates for the treatment in 15 young men with premature androgenetic
      alopecia. Hormonal analysis discovered a significantly lower plasma level of
      sexual binding globulin (SHBG) and FSH and nearly significantly higher
      concentration of 17 alpha-hydroxyprogesterone. These data resemble those in the
      hormonal pattern of women suffering from the syndrome of polycystic ovaries
      (PCOS). The finding of premature balding as the possible male phenotype hormonal
      equivalent of polycystic ovaries is in concordance with several pedigree studies
      in kindreds with PCOS, which have suggested a genetic basis of this syndrome in
      some families in which balding and pilosity was frequent in male members.

PMID- 10953628
TI  - [The postwar years at the 1st Stomatology Clinic at Charles University in
      Prague].

PMID- 10953629
TI  - [Abdominal and gluteal circumference as diagnostic criteria for the distribution
      of fat in childhood, adolescence and early adulthood].
AB  - Two essential nutritional and anthropological parameters--abdominal (waist) and
      gluteal (hip) circumferences were measured during the period of growth by the
      method according to Martin [Martin & Saller, 1957] and Knussmann [1988]/M 62(1);
      M 64(1)/. 33,562 Czech probands of both sexes age 1.5 to 20 years were examined.
      Percentile networks of both circumferences were constructed for males and
      females.

PMID- 10953630
TI  - [Nutritional status and problems with obesity in relation to educational status
      in young people in the Czech Republic].
AB  - The cross section study was performed with the aim to detect health prone
      nutritional behaviour and describe its relationship to the education in the
      groups of 20-25 years old people. Two groups: 449 undergraduate medical students
      (UG) and 116 non-graduate control people (C) were compared in respect of their
      food habits (food frequency questionnaire), nutrition (3 days dietary records
      data) and health nutritional state (measurement of body weight, height,
      percentage of body fat using Harpenden calliper). UG male performed higher energy
      intake, however, they did not differ in BMI, but they showed lower proportion of
      body fat ?95% CI:(-4.22; -4.18)% of body content?, probably due to higher
      physical activity. UG female performed lower energy intake and lower body mass
      index in comparison to C ?95% CI:(-4.18; -4.8) kg/m2?. CONCLUSION: Higher level
      of education is associated with health prone behaviour and is reflected on health
      nutritional state already in age of early adulthood.

PMID- 10953631
TI  - [Leptinemia in obese children during health spa therapy].
AB  - Leptin values were investigated during four week treatment of obese children by
      weight reducing diet and dosed physical activity, controlled by sport-testers.
      Leptin values correlated significantly with BMI and HDL-cholesterol at the
      beginning of spa treatment and at the end of treatment. Values of leptin at the
      beginning of treatment correlated with fasting insulinaemia. There were no
      changes in leptin values during oral glucose tolerance test. Significant decrease
      of BMI, total cholesterol, LDL-cholesterol, triglycerides, systolic BP and leptin
      values appeared after four week treatment. Leptin values did not correlate with
      total or LDL-cholesterol at the beginning or at the end of the treatment and
      leptin values were not predictive for development of atherosclerosis.

PMID- 10953632
TI  - [Prevalence of obesity in selected subpopulations in the Czech Republic].
AB  - The authors present the results of an epidemiological study focused on monitoring
      selected anthropometric parameters which characterize the nutrition state. 933
      volunteers altogether, in age group 19-60 years, were tested in the study.
      Anthropometric parameters such as weight, height, skinfold thickness and abdomen
      circumference were measured. BMI and fat tissue percentage were calculated on the
      basis of gathered data. Overweight was detected in 67.5% of monitored men,
      obesity in 17.0% of them. Overweight was detected in 50.0% of women, obesity in
      18.9% of them. Waist circumference exceeding 102 cm was measured in 41.2% of men
      and waist circumference exceeding 88 cm in 41.7% of monitored women. The
      unfavourable nutrition state correlates with a high occurrence of cardiovascular
      and metabolic diseases appearing within the Czech population.

PMID- 10953633
TI  - [Metabolic and hormonal links in obese individuals with and without symptoms of
      syndrome X].
AB  - We carried out statistical analysis of biochemical, anthropometric and anamnestic
      values at the first contact with 114 patients in the specialized obesity unit. We
      evaluated metabolic state of different groups varying in the presence of risk
      factors of atherosclerosis. We disclosed statistically significant differences
      between those groups, enabling evaluation of the severity of state and early
      decision on suitability and urgency of treatment.

PMID- 10953634
TI  - [Effect of fat distribution on lipoprotein composition and parameters of
      lipoperoxidation].
AB  - Fat distribution, not overweight and obesity per se, are supposed to be
      associated with hemodynamic, hemostatic and other metabolic disturbances (insulin
      resistance, hyperuricemia and dyslipidemia). Moreover, obesity increases the
      total risk of cardiovascular disease. Oxidative modification of lipoproteins,
      especially of LDL, is supposed to play a key role in the initiation and
      progression of atherosclerosis. Therefore we analysed VLDL a LDL composition and
      Cu(2+)-catalyzed conjugated diene formation in both lipoprotein fractions in
      patients with intraabdominal fat accumulation and in control group. Patients (33,
      12 M/21 F) with intraabdominal fat accumulation (WHCR 1.00 for men, 0.85 for
      women) revealed, in comparison with control group (72, 47 M/25 F), after
      adjustment for the same age, increased plasma total cholesterol, apolipoprotein
      B, non-esterified fatty acid concentrations, and systolic blood pressure as well.
      In the group of patients increased levels of cholesterol, triglycerides,
      phospholipids, proteins and apolipoprotein B (only in the fraction of VLDL) were
      found in the both VLDL and LDL fractions. In this group of patients increased
      concentrations of conjugated dienes in VLDL and decreased length of lag phase of
      VLDL were found. Parameters of conjugated diene formation of LDL (basal
      absorbance, length of lag phase, propagation phase) did not differ significantly
      from controls. Concomitantly, persons with intraabdominal fat distribution showed
      decreased titres of antibodies against oxidative modified LDL. The results
      indicated that the patients with intraabdominal fat accumulation revealed not
      only adverse composition of VLDL and LDL particles, but also increased VLDL
      oxidation and oxidability.

PMID- 10953635
TI  - [Insulinemia, fatty acids in plasma lipids and lipoproteins and oxidation of VLDL
      and LDL in hyperlipidemia].
AB  - Both insulin resistance and hyperlipidaemia are connected with an increased
      oxidative stress, playing a significant role in the development of
      atherosclerosis. A significant event in the process being the oxidative
      modification of the lipoproteins, especially LDL. Aim of the study was to analyse
      relationships between the fatty acid composition of the plasma cholesteryl esters
      (CE), triglycerides (TG) and phosphatidylcholine (PC) and of the separated LDL,
      insulinaemia and oxidability of both VLDL and LDL particles. We have observed the
      group of 75 patients with hyperlipidaemia (52 men and 23 women), which was
      divided in the two subgroups after the basal insulinaemia (more resp. less than
      13 mU/l). Fasting hyperinsulinaemia of the probands with normal glucose tolerance
      served as a marker of an insulin resistance. Patients with both hyperlipidaemia
      and basal hyperinsulinaemia were characterized by a significantly higher
      concentration of TG, apolipoprotein B in LDL, and lower concentration of
      cholesterol in HDL, especially in HDL3. We have observed only marginally
      significant elevation of concentration of the dihomo-gammalinolenic acid (DGLA)
      in plasma PC and also higher concentrations of alpha-linolenic and lower of
      arachidonic acid (AA) and in LDL-CE in the hyperinsulinaemic group. We have also
      found significantly positive correlations between the stearic acid in plasma PC,
      alpha-linolenic acid in plasma TG on one hand and the basal insulinaemia on the
      other hand. Significant positive correlation was also found between the ratio
      docosahexaenoic/docosapentaenic acid and insulinaemia in 120 min of oral glucose
      tolerance test. Significant negative correlation was observed between the ratio
      AA/DGLA and basal insulinaemia. Analysing the lipoperoxidation of VLDL and LDL
      using the method of conjugated diene kinetics we have found statistically non
      significant decrease of lag phase duration of LDL and VLDL (their oxidability).

PMID- 10953636
TI  - [Effect of diabetes in the first year after gastric banding].
AB  - Initial hormonal and metabolic investigation was performed in a group o 51
      patients (mean age 41 years and body mass index--BMI 45.1 kg/m2) referred to
      gastric banding for morbid obesity. Patients were followed for one year period
      after surgery. Using multiple linear regression following parameters influencing
      BMI change were identified. Negative influence on BMI reduction: high insulin,
      presence of diabetes, low T3/T4 ratio. Positive influence on BMI reduction high
      triglycerides level, positive family history of diabetes. It is possible to
      identify patient's prognosis after gastric banding using metabolic and hormonal
      investigation. This investigation should be performed in every patient.

PMID- 10953637
TI  - [Effect of physical activity on serum leptin levels].
AB  - Leptin is a protein hormone produced predominantly by adipocytes. Its serum
      concentrations usually reflect the total body fat content i.e. they are higher in
      obese than in lean subjects. The aim of our study was to follow the influence of
      the regular hard physical training on the serum leptin levels. Therefore, the
      serum leptin levels in top rugby players, top race walkers and age and gender
      matched control group were compared. The relationship between serum leptin
      concentrations and body mass index and body fat content was also studied. It was
      found that serum leptin levels in rugby players were significantly higher than in
      race walkers group, but lower than in control one. Serum leptin levels in race
      walkers were lower than those of rugby players and of control group. The body fat
      content in race walkers was lower than in resting two groups. There was no
      significant difference in body fat content between control and rugby players
      group. Serum leptin levels correlated positively with body mass index and body
      fat content both in control and in rugby players group. No statistically
      significant relationship was found between leptin and body mass index or body fat
      content respectively in race walkers group. We conclude that serum leptin levels
      in top sportsmen are lower than in non-sporting healthy age and gender-matched
      controls. The lower leptin levels in top sportsmen are probably in part the
      result of lower body fat content and in part the result of complex neurohormonal
      adaptation on the long term physical training.

PMID- 10953638
TI  - [Case reports of morbid obesity].
AB  - Morbid obesity (BMI over 40 kg/m2) is typically complicated by many serious
      diseases including early death. Using 7 case studies of morbid obese patients we
      are documenting severe polymorbidity of these persons including severe
      manifestation of metabolic syndrome. Using adequate therapy, e.g. gastric
      banding, risk of these patients can be reduced. Some parts of metabolic syndrome
      can be documented in adolescent children of these patients. The aim of this study
      is to show the importance of early intervention in patients with morbid obesity.

PMID- 10953639
TI  - Respiratory quotient in obesity: its association with an ability to retain weight
      loss and with parental obesity.
AB  - A high fasting respiratory quotient (RQ) was observed during the treatment by
      very low calorie diet (VLCD) in obese patients who regained weight at two-year
      follow-up (weight regainers) or in those who exhibited repeated cycles of weight
      loss with a subsequent weight regain (weight cyclers). In contrast obese patients
      who succeeded to retain the weight loss achieved initially by the VLCD at 2-yr
      follow-up (weight losers) or those who did not exhibit weight fluctuations
      (weight noncyclers) were characterized by a significantly lower RQ. Therefore a
      high fasting RQ during the VLCD treatment should be considered predictive of body
      weight gain. Resting metabolic rate (RMR) expressed per kg fat free mass (FFM)
      did not influence body weight changes. A high RQ revealed in obese subjects
      reporting parental obesity and a low fasting RQ observed in those obese without
      family history of obesity suggest a role of hereditary factors in the ability to
      oxidize fat in severely obese subjects. In contrast, parental history of obesity
      did not affect RMR in severely obese individuals.

PMID- 10953640
TI  - [Changes in selected biochemical parameters during a low-calorie reducing diet].
AB  - AIM OF THE STUDY: Assessment of the effect of short term modified low calorie
      diet on body weight and body mass index (BMI). Assessment of the effect of
      modified low calorie diet on blood lipids and some biochemical parameters.
      METHODS: Before and after diet: body weight, BMI, whole blood count, platelet
      count, serum cholesterol, triglycerides and HDL cholesterol, serum creatinine,
      uric acid, urea, bilirubin, AST, ALT, pH of urine and atherogenic index (CHOL
      HDL/HDL). PATIENTS: 11 male, mean age 52 years and 19 female, mean age 53.3
      years. THERAPY: Modified diet 14 days, 3.3 MJ daily, vitamins and minerals.
      RESULTS: No significant difference was observed in platelet count, serum
      creatinine, urea, bilirubin, AST, ALT, pH of urine, HDL cholesterol and
      atherogenic index before and after modified low calorie diet. Significant loss of
      body weight and decrease of BMI, cholesterol and triglycerides occurred after
      modified diet. Serum uric acid significantly increased after weight loss.
      CONCLUSION: The present result's shows that a drop of serum cholesterol and
      triglycerides follows a significant loss of body weight after modified diet. Our
      result's shows a significant increase of uric acid levels after weight loss.
      There was no effect of body weight loss on other biochemical parameters.

PMID- 10953641
TI  - [Ultrasound measurement of visceral fat in obese patients (changes in certain
      parameters during an outpatient reducing program)].
AB  - Abdominal type of obesity is linked to risk factors of metabolic diseases. The
      determination of visceral fat with the ultrasound assessment by Armellini is a
      very simple method. 55 obese patients were such examined including other
      parameters during the weight reduction. The results of our small experimental
      group are shown in the Tab. 1 and 2.

PMID- 10953642
TI  - [Dietary habits in obese individuals before ambulatory obesity treatment].
AB  - Resting energy expenditure, using indirect calorimetry, and food habits by the
      food frequency questionnaire, were measured in randomly selected 200 obese people
      (body weight 102 +/- 23 kg, age 41 +/- 15 yrs) during their first appointment in
      the Centre for obesity treatment. All were educated in low calorie diet (LCD = 5
      MJ) regime at the same way. After 30 months the obese people from the highest and
      the lowest quartile according to the percentage of weight loss (derived as a
      percentage of their initial body weight) were compared. There was not found any
      statistical difference in frequency of particular commodities intake, only higher
      probability of good weight reduction was confirmed in obese with higher body
      weight (p < 0.003) and higher resting energy expenditure (p < 0.02) on the
      beginning of the LCD treatment. This study has demonstrated that food habits
      assessed according food frequency questionnaire has not predictive value to
      distinguish between successful or non-successful compliance with very low calorie
      diet.

PMID- 10953643
TI  - [Fatty acid composition of domestic dietary fats].
AB  - Trans fatty acids (TFA) were analyzed by capillary gas chromatography in four
      groups of edible fats available on the Prague market. In animal fats, 1.9-2.5%,
      2.8-5.5% and 11.3-13.5% TFA were found in the lard, butter, and butter enriched
      by vegetable fat, respectively. In shortenings, TFA content varied between 0.5
      and 38%, in margarines from 0.6 to 13% and in table fats from 1.4 to 27%.

PMID- 10953645
TI  - [Hypersomnia].

PMID- 10953644
TI  - [Effect of diet therapy and increased physical activity on risk factors for
      atherosclerosis in obese patients with ischemic coronary heart disease].
AB  - BACKGROUND: Obesity is associated with coronary artery disease. Intensive weight
      reducing therapy can result in improving outcome of patients after myocardial
      revascularization. METHODS AND RESULTS: 180 patients were treated by hypocaloric
      diet and physical training program lasting 28 days. Changes in body mass index
      (BMI), and serum levels of triglycerides were significant, serum level of
      cholesterol didn't significantly change (partially due to long lasting lipid
      lowering therapy with simvastatin before treatment by training and diet).
      Decrease of BMI was strongly associated with decrease of serum levels of
      triglycerides. CONCLUSIONS: This study supports assumption that hypocaloric diet
      and physical training can improve outcome of patients with coronary heart disease
      by influencing risk factors of atherosclerosis.

PMID- 10953646
TI  - [Why do we sleep? Contributions from animal research].
AB  - Despite the almost ubiquitous presence of sleep and the sleep stages nonREM and
      REM sleep in mammals and birds, the functions of sleep still remain elusive.
      Several promising approaches may shed light on this problem. Thus investigation
      of sleep-like states such as hibernation and torpor have shown that these states
      are more similar to sleep deprivation than to sleep. Furthermore, sleep-like
      states, which are homeostatically compensated for after rest deprivation have
      been found in Drosophila. These results allow to search for genes and gene
      products which change as a function of the vigilance states in these more simpler
      organisms. Thereafter, homologous genes can be investigated in mice.

PMID- 10953647
TI  - [Hypersomnia--etiology, clinic, diagnosis and therapy of excessive sleepiness].
AB  - Hypersomnia (excessive sleepiness) refers to an increased sleep propensity with a
      subjective craving for sleep, involuntary naps and "sleep attacks" during the day
      and/or prolonged nighttime sleep with sleep drunkeness. Excessive sleepiness
      should be separated from fatigue and lack of energy associated with a variety of
      medical and psychiatric diseases. Hypersomnia is reported by 2-5% of the adult
      population and can lead to poor work, accidents and neuropsychiatric
      disturbances. Sleep apnea syndrome (SAS), narcolepsy, chronic sleep deprivation
      (insufficiency), and restless legs/periodic limb movements in sleep syndrome
      (RLS/PLMS) represent the most common causes of hypersomnia. The diagnosis of
      these conditions can often be suspected on clinical grounds. However, an
      overnight polysomnography and a multiple sleep latency test are often
      additionally required for definite diagnosis. Treatment options include nasal
      CPAP for SAS, stimulants for narcolepsy, sleep prolongation for sleep
      insufficiency, and dopaminergic agents for RLS/PLMS.

PMID- 10953648
TI  - [From simple snoring to sleep apnea syndrome--clinical spectrum].
AB  - About 40% of adults are habitual snorers. 2% of women and 4% of men between 30
      and 60 years of age present additional sleep disordered breathing. There is a
      continuous spectrum from simple to disease-causing snoring ranging from merely
      disturbing noises to pharyngeal obstructions and breathing pauses. Repetitive
      episodes of upper airway obstructions lead to frequent arousals from sleep. Sleep
      fragmentation is responsible for non-refreshing sleep and subsequent excessive
      daytime sleepiness resulting in reduced performance at work, social problems and
      a higher risk for accidents. Furthermore there is a correlation between arousals
      and cardiovascular abnormalities. Anatomic narrowing of the upper airway or
      hypotonia of the orpharyngeal dilator muscles favour collapse of the
      oropharyngeal walls. Obstructive sleep apnea syndrome is characterized by
      repetitive oxyhemoglobin desaturations during sleep recorded by pulseoximetry.
      Polygraphy quantifies the average number of apneas and hypopneas which occur
      during one hour of sleep (apnea-hypopnea index = AHI). In upper airway resistance
      syndrome (= UARS), upper airway resistance is increased, but pharyngeal
      obstruction is not complete. Saturation doesn't decrease significantly, but
      arousals with consecutive sleep disruption still occur. Polysomnography is a
      comprehensive study including EEG-, EOG- and EMG-recordings. Sleep stages and
      events can be scored to evaluate sleep architecture, sleep efficiency and sleep
      fragmentation.

PMID- 10953649
TI  - [Falling asleep at the steering wheel--a dangerous sequel of sleep apnea].
AB  - Excessive sleepiness is a common but underrecognised and preventable cause of
      road traffic accidents. Acute and chronic sleep deprivation, inadequate sleep
      hygiene, and sleep disorders are important causes of hypersomnolence. Since the
      latter is one of the cardinal manifestations of the obstructive sleep apnoea
      syndrome, affected patients are at particular risk of being involved in traffic
      accidents. Counselling of hypersomnolent drivers on appropriate behavioural
      modification, early diagnosis and treatment of sleep disorders, as well as
      information of the public on the risks of accidents related to sleepiness are
      important preventive measures.

PMID- 10953650
TI  - [Diagnosis of sleep apnea syndrome--role of family practitioner].
AB  - The obstructive sleep apnea syndrome is a highly prevalent and underdiagnosed
      disease. Repetitive arousals due to upper airway obstruction lead to hypersomnia.
      Due to the insidious onset, patients often underestimate the severity of their
      symptoms. Relatives can give helpful additional informations and should be
      involved in history taking and motivation for treatment. In general, GP's are
      confronted with the problem of fatigue and hypersomnia in the first line. They
      play the most important role in selecting patients for further investigations.
      The patient history helps to separate hypersomnia from fatigue. Hypersomnia
      indicates falling asleep at daytime in unappropriate situations, especially when
      the subject is passive. Often, a multidisciplinary approach including respiratory
      physicians, ENT specialists, orthopedic dentists and neurologists is warranted.
      Anatomic narrowing of the upper airway must be ruled out by clinical
      investigation. Overnight sleep studies detect apneas/hypopneas and repetitive
      arousals. Continuous positive airway pressure, applied by a nose mask and a flow
      generator remains the mainstay of therapy. Motivation, counseling and
      troubleshooting especially in the beginning of this therapy are of outmost
      importance. Ongoing research aims to improve comfort of nose masks and optimize
      function of flow generators.

PMID- 10953651
TI  - [Effectiveness of nasal CPAP-treatment (continuous positive airway pressure)].
AB  - Nasal continuous positive airway pressure (n-CPAP) is an effective treatment for
      the obstructive sleep apnea syndrome (OSAS). It is currently regarded as the
      first line therapy for OSAS. The principal indication for n-CPAP treatment is
      daytime sleepiness. Nasal-CPAP improves daytime sleepiness dramatically in severe
      cases and the effect is objectively measurable with the multiple sleep latency
      test (MSLT). It is noteworthy that n-CPAP also improves symptoms, subjective
      daytime sleepiness, cognitive function, IQ, mood, quality of life and driving
      ability already in patients with mild sleep apnea with an apnea/hypopneaindex
      (AHI) between 5 and 15 per hour of sleep during overnight polysomnography.
      Although not yet 100% robust, there is clear evidence that patients with OSAS
      have an increased frequency of systemic hypertension. Some early and imperfect
      studies suggest that CPAP reduces cardiovascular and cerebrovascular outcomes;
      however unequivocal evidence that n-CPAP reduces mortality is still awaited.
      There is now good evidence that treatment with n-CPAP reduces the two- to
      sevenfold increased risk of road accidents of untreated patients with OSAS. In
      summary, there exists abundant evidence today that n-CPAP is an efficient therapy
      for symptomatic patients with the obstructive sleep apnea syndrome. A trial with
      n-CPAP is therefore justified in all symptomatic patients. Based on the large
      number of randomized controlled trials of n-CPAP a therapeutic trial is indicated
      even in only mildly symptomatic patients with OSAS. Nasal-CPAP use and outcomes
      of therapy can be improved by provision of an intensive CPAP-education and
      support program.

PMID- 10953652
TI  - [Noninvasive alternatives to CPAP in therapy of obstructive sleep apnea
      syndrome].
AB  - Non-surgical treatment of the sleep apnea syndrome comprises behavioral
      modification such as sleep hygiene, weight reduction, and positional training as
      an adjunct to standard therapy with continuous positive airway pressure (CPAP)
      applied via a nasal mask. For patients who cannot tolerate or are not willing to
      use CPAP for psychological or other reasons, removable intraoral appliances that
      advance the mandible during sleep are a valuable treatment alternative.
      Randomised controlled trials have confirmed effectiveness of intraoral appliances
      in relieving symptoms and measured sleep and respiratory disturbances. Side
      effects including hypersalivation, mucosal dryness, tooth and temporo-mandibular
      joint discomfort are common but usually mild. To timely detect effects of oral
      appliances on occlusion and on the temporo-mandibular joint longterm orthodontic
      monitoring is advisable.

PMID- 10953653
TI  - [Surgical options for treatment of snoring and sleep apnea].
AB  - Simple snoring and obstructive sleep apnea are part of a complex disease process
      with a high prevalence. Surgical treatment options have been developed by
      otolaryngologists over the last decades. Knowledge of different surgical
      procedures is required to address the various findings during preoperative
      assessment. Patients with nasal airway blockage due to septal deviation, large
      turbinates or polyps may benefit from endonasal surgery. Obstructive tonsils,
      palatal webbing, and an enlarged uvula require surgical approaches including the
      soft palate and tonsils. The controversy on indications and contraindications for
      the standard uvulopalatopharyngoplasty, laser-assisted uvulopalatoplasty and the
      use of radiofrequency is still ongoing. Dysgnathia may require maxillofacial
      surgery and macroglossia may be treated with reductive surgery of the tongue.
      Narrowing of the posterior airway space at the level of the tongue base may be
      addressed by advancement of the bony insertion of the genioglossus muscle and
      suspension of the hyoid. A new procedure is the suspension of the tongue with a
      non-resorbable suture fixed to a mandible anchored screw. Our first promising
      results need to be re-evaluated over time.

PMID- 10953654
TI  - [Central sleep apnea syndrome and Cheyne-Stokes respiration].
AB  - This overview discusses pathogenesis, clinical presentation, prognostic
      implications and therapy of central sleep apnea with special reference to Cheyne
      Stokes-Respiration or periodic breathing. In contrast to obstructive sleep apnea
      due to upper airway collapse during sleep, central sleep apnea (CSA) is mainly
      due to an instability of the breathing control system. Causes of central sleep
      apnea include alveolar hypoventilation disorders, heart failure, neurologic and
      autonomic disorders and idiopathic forms of CSA. Patients with idiopathic CSA
      often complain of insomnia and awakening during sleep but may also suffer from
      daytime sleepiness. Cheyne-Stokes-Respiration or peridic breathing is often
      associated with heart failure and neurological disorders especially those
      involving the brainstem. In heart failure periodic breathing has enormous
      prognostic implications. Treatment options for central sleep apnea are oxygen
      supplementation, medical therapy (i.e. acetazolamide) and CPAP. For patients with
      central sleep apnoea associated with alveolar hypoventilation nasal ventilation
      is treatment of choice. Newer nasal ventilation techniques (BiPAP, AutoSetCS) are
      under investigation for heart failure patients with Cheyne-Stokes-Respiration.

PMID- 10953655
TI  - [Sleep apneas in children].
AB  - There are many causes leading to breathing disorders in children. In the newborn
      period the immature central regulation of breathing can result in a pattern with
      apneas and bradycardias most commonly seen in the very premature infant.
      Therefore, during hospital stay many of these very tiny preterms and some of the
      very ill term infants do have severe apneas and do need medication and or
      mechanical support (nasal CPAP, positive pressure ventilation). In the first two
      to three months of life central dysmaturity can persist in some infants and
      apneas of infancy can occur further on. Infants with prolonged apneas and
      symptoms like paleness, cyanosis, stiffness or limpness are often investigated,
      treated or monitored. At the age of two to six, every tenth child is a loud
      snorer. Every fifth snorer at this age suffers from a severe upper airway
      obstruction. Factors that decrease pharyngeal size or increase pharyngeal
      compliance may lead to obstruction. Adenotonsillar hypertrophy is the most common
      associated condition, craniofacial disorders, central nervous system and
      neuromuscular problems and less obesity are disposing factors. Children may
      present nocturnal symptoms like snoring, difficult breathing or disturbed sleep,
      but most of them have daytime problems as initial complaint such as
      hyperactivity, behavioral problems, growth failure, poor school performance.
      Excessive daytime sleepiness is not so common in young children. The childhood
      obstructive sleep apnea syndrome is a common and serious problem. Children with
      symptoms suggesting severe obstruction should be evaluated and treated. Most
      children are cured by adenotonsillectomy whilst some require further therapy.

PMID- 10953656
TI  - [Differentiation of malignant and non-malignant origin of ascites by
      determination of levels of cholesterol and lactate dehydrogenase in ascitic fluid
      is not absolute].
AB  - The authors Castaldo et al. (Clin. Chem., 1994, 30: 478-83) state, that the
      ascitic lactate dehydrogenase and ascitic cholesterol association correctly
      identified 100% of malignant ascites from ascites associated with cirrhosis
      and/or hepatocellular carcinoma, with help of stepwise multiple linear
      discriminant analysis. The free software Capsules--Ascites is via internet
      available (http:?www.leeds.ac.uk/acb), which use the mathematical formula from
      this article. As we argue, Castaldo's state is not correct. Three independent
      multidimensional statistical methods--bivariate reference regions (program EVAL
      KIT), cluster analysis (program BioAnalyst), geometrical distance classification
      (program GEODICLA) applicated on Castaldo's original data showed that lactate
      dehydrogenase and cholesterol have not satisfactory absolute discriminative power
      between malignant from nonmalignant ascites in general, but the probability to
      determinate the right diagnosis is about 91-93%. Research conducted in correctly
      selected probands should provide information which is valid not only for the
      selected sample but for the entire population, to achieve more generally valid
      conclusions, useful for practical decisions. In addition, in the compiled table
      show we sensitivity and specificity of different laboratory parameters publicated
      in 11 original articles in the nineties, all with diagnostic efficiency less
      100%.

PMID- 10953657
TI  - [Chronic venous insufficiency].
AB  - The author investigated in a group of 224 patients selected at random (380
      extremities), indicated for different reasons for examination of the venous
      system of the lower extremities by coloured duplex and triplex sonography, the
      prevalence, site and clinical manifestations of deep venous insufficiency. Only
      21.1% patients indicated for examination on account of clinical signs of deep
      venous thrombosis had objective signs of the disease, while almost half (47.7%)
      suffered from venous insufficiency. Venous insufficiency was detected also in a
      large percentage (59.9%) of patients without clinical symptoms. In the great
      majority of patients (99.8%) combined insufficiency was found affecting
      concurrently the femoral and popliteal vein and sometimes also the iliac vein.

PMID- 10953658
TI  - [Regression of deep venous thrombosis].
AB  - The submitted prospective randomized study investigated the way and rate of
      regression of deep venous thrombosis of the lower extremities during a six-month
      out-patient follow up. On discharge on the 5th to 10th day after establishment of
      the diagnosis the thrombosis had not disappeared in any of the patients, in two
      patients progression was observed despite anticoagulant therapy. After three
      months 4.8% thromboses were recanalized, after 6 months 33.3%. In 33.3% of
      patients recanalization in a distal-proximal direction was found, in 19% in a
      proximal-distal direction and in 33.3% recanalization occurred throughout the
      thrombotic occlusion. Thromboses recanalized more quickly in patients under 50
      years of age.

PMID- 10953659
TI  - [Familial hypercholesterolemia: do we know how to diagnose it correctly?].
AB  - Familial hypercholesterolaemia is a serious inborn disease of lipoprotein
      metabolism with a high risk of early cardiovascular complications. The cause of
      the disease is a congenital defect of LDL receptors. In adults with familial
      hypercholesterolaemia practically always pharmacotherapy with hypolipaemic agents
      is indicated. The prerequisite for starting lifelong medication in primary
      prevention of ischaemic heart disease is a correct diagnosis of this disease. The
      latter involves in addition to clinical and genealogical examinations, above all
      correct interpretation of blood lipids in relation to age and the relationship of
      probands in the affected family. At present the diagnostic process is improved
      greatly by DNA analysis. The author mentions also exact clinical and laboratory
      criteria for classification of patients with familial hypercholesterolaemia into
      groups.

PMID- 10953660
TI  - [The hepatic form of Wilson's disease in young patients].
AB  - Wilson's disease (WD) is a hereditary disorder of the copper metabolism with very
      varied clinical and biochemical symptoms. Hepatic and neurological forms are the
      most frequent manifestations of this rare disease. In schoolchildren and
      adolescents symptoms of liver damage predominate. In a retrospective study 19
      patients were evaluated with biochemical signs of hepatopathy manifested before
      the age of 18 years. The diagnosis of WD was established at the age of 7 to 27
      years. One female patient was admitted with fulminant hepatic failure which was
      treated by acute transplantation of the liver in the Institute of Clinical and
      Experimental Medicine in Prague. Only 9 of 18 patients with chronic hepatic
      affection at the time of diagnosis met the Sternlieb diagnostic criteria. These
      patients had reduced ceruloplasmin levels (0.08-0.18 g/l) and a high copper
      content in the hepatic dry matter (783 ug/g +/- 323 [SD]). In the remaining 9
      patients the ceruloplasmin level was normal, however, in 8 a high copper content
      of the hepatic dry matter was found (696 ug/g (+)- 352[SD]. The last patient from
      this group had Kayser-Fleischer's (K-F) ring. It was possible to confirm the high
      copper content in the hepatic dry matter only after one year's penicillinamine
      treatment because at the time of the diagnosis poor coagulation did not permit to
      perform a liver biopsy. There was a statistically significant difference in the
      copper content of the hepatic dry matter in patients meeting and not meeting
      Sternlieb's criteria. Statistically significant differences between both groups
      were found in the plasma copper levels and in the 24-hour urinary copper
      excretion. Histological examination of the liver under a light microscope
      revealed findings from minimal changes associated with the presence of glycogen
      nuclei in hepatocytes to the picture of active chronic hepatitis. In all 19
      patients the gene mutation H1069Q was examined and the results were positive in
      39.8%. In 3 asymptomatic patients it was present in the homozygous form.
      CONCLUSION: Early detection of the atypical form of WD remains very difficult.
      The gold standard is still in all cases assessment of copper in the dry liver
      tissue. In the near future an important place will be held also by direct DNA
      analysis although its use is limited not only by the large number of known
      mutations but also by the financial costs of the method.

PMID- 10953661
TI  - [The short bowel syndrome].
AB  - The authors demonstrate on case-histories their experience with short-loop
      syndrome which develops after extensive resections of the small intestine. The
      clinical picture of the syndrome is characterized by diarrhoea, steatorrhoea,
      maldigestion and malabsorption with loss of body weight. Non-surgical treatment
      of the syndrome copies its different stages. The objective of conservative
      therapy is above all to preserve the nutritional integrity of the organism and
      gradual adaptation of the gut which will make eventually a change to oral intake
      possible. This adaptation takes 1 to 2 years. Last not least, treatment should
      eliminate the diarrhoea. The authors demonstrate on examples that properly
      conducted treatment prevented the development of malnutrition, contrary to
      another case where the sequelae of surgery were underestimated and the patient
      developed cachexia and pernicious anaemia.

PMID- 10953662
TI  - [A dissecting aortic aneurysm in a female patient with Turner syndrome].
AB  - Female phenotype, sexual infantilism, small stature and stigmatization are
      typical for patients with Turner's syndrome (TS). The most frequent
      cardiovascular manifestations in these patients are a bicuspidal aortal valve and
      coarctation of the aorta. In 5% patients dilatation of the aorta is found which
      can develop into a dissecting aneurysm. In the submitted case-history the authors
      describe a 34-year-old patient where the diagnosis of TS was proved only in adult
      age at the time when a dissecting aneurysm of the aorta was detected. The
      submitted case-history supports the recommendation of regular echocardiographic
      check-up examinations of patients with TS.

PMID- 10953663
TI  - [24-hour ambulatory blood pressure monitoring].
AB  - 24-hour ambulatory blood pressure monitoring (ABPM) is the exact, fully automatic
      and noninvasive method for evaluation of the 24-hour hemodynamic profile of the
      subject by multiple and regular blood pressure and heart rate measurement. In
      comparison with causal blood pressure measurement, ABPM allows the definition of
      daytime and nighttime blood pressure averages, diurnal changes of blood pressure,
      localization of periods of the most frequent appearance of hypertensive values,
      specification of hypertensive load, percent time elevation and diagnosing of
      white coat phenomenon. The use of all mentioned findings leads to the improvement
      of blood pressure control in patients with resistant hypertension, polymorbidity,
      helps to analyze paroxysmal hypertension, verify diagnosis of the hypertension in
      patients with borderline or high normal blood pressure. The final profit is the
      reduction of the target organ damage and reduction of cardiovascular morbidity
      and mortality. Definite diagnosis of the white coat phenomenon markedly decreases
      consumption of the antihypertensive drugs. In addition, this method enables
      better evaluation of hypotensive syndromes and is very helpful in the
      investigation of physiology of blood pressure regulation, biorhythms and in
      pharmacodynamical studies of the new antihypertensives.

PMID- 10953664
TI  - [Is nebulized ipratropium bromide effective in the treatment of exacerbations of
      chronic obstructive pulmonary disease?].
AB  - The author administrated to 20 patients hospital on account of exacerbation of
      chronic obstructive pulmonary disease nebulized ipratropium bromide 0.5 mg on
      admission. Nebulized was repeated, using the same dose after 30 mins. The PEF
      value increased significantly after the first and second nebulization. After the
      two nebulizations dyspnoea was alleviated. The value of the respiration rate was
      significantly lower after both nebulizations as compared with the value before
      treatment. PaO2 increase significantly as compared with the value before
      treatment. PaO2 and the pulse rate did not change. An undesirable effect was
      recorded in one patient. Ipratropium bromide administration in effective and
      safe.

PMID- 10953665
TI  - [Endothelins and ischemic heart disease].
AB  - Endothelins (ET) comprise a group of substances which are produced and have a
      regulatory function in different systems of the organism. The main cardiovascular
      ET is ET-1 which is so far the most potent vasoconstrictor substance. ET is
      important in the early stages of atherosclerosis as it is a strong chemical
      attractant of monocytes and macrophages and causes endothelial and vasomotor
      dysfunction. In later stages of atherosclerosis it can affect the firmness and
      integrity of the fibrous part of the atherosclerotic plaque. During myocardial
      infarction the ET level rises and this leads to vasoconstriction and reduction of
      the fibrillation threshold. In coronary angioplasty (PTCA) the ET-1 level rises
      depending on the applied mechanical stress. ET can participate in the formation
      of the neointima and the development of restenosis. ET increases also immediately
      after an aortocoronary bypass (CABG) and after reperfusion. Higher ET levels were
      found in patients with a positive ECG and echocardiographic loading test. In the
      latter after CABG normalization of ET was found. Raised ET levels were recorded
      also in patients where a coronary vasospasm can be provoked, in Prinzmetal's
      angina pectoris, coronary syndrome X, atrial tachystimulation. In unstable angina
      pectoris big-ET is elevated, the increase of the ET-1 level is not unequivocal.
      Stable angina pectoris does not affect ET-1. In the treatment of atherosclerosis
      for the selective ETA blocker reduction of the number and size of macrophage and
      foam cells was proved. In acute myocardial infarction a favourable effect for the
      non-selective ETA/ETB blocker and for the selective ETA blocker was found. In the
      treatment of restenosis after PTCA blockers of selective ETB receptors and
      inhibitors of endothelin converting enzyme seem hopeful. Th non-selective ETA/ETB
      blocker bosentan is in the stage of clinical tests and seems to be safe and
      perspective.

PMID- 10953667
TI  - [The future of internal medicine, cardiology and patients].

PMID- 10953666
TI  - [Endothelins and chronic cardiac insufficiency].
AB  - Endothelins (ET) comprise a group of substances which are produced and have
      regulatory functions in different systems of the organism. The main
      cardiovascular ET is ET-1 which is so far the most potent vasoconstrictor
      substance. In the pathophysiology of cardiac insufficiency ET-1 promotes cardiac
      hypertrophy, is involved in vasoconstriction, delayed relaxation and reduced left
      ventricular contractility. The ET-1 level correlates with pulmonary vascular
      hypertension. By vasoconstriction of renal arteries ET leads to volume retention.
      Big-ET is a very efficient neurohumoral marker in the diagnosis of developed
      cardiac failure which can lead to more accurate prognostic stratification. ET-1
      is probably important for assessment of the diagnosis of cardiac insufficiency
      only in severe cardiac failure. The favourable effect of ET block in cardiac
      insufficiency was proved for the non-selective ETA/ETB blocker and selective ETA
      blocker. The selective ETB blocker has an adverse haemodynamic effect in
      treatment of heart failure but by suppression of aldosterone it can prevent fluid
      retention. In the treatment of cardiac failure blockers of endothelin converting
      enzyme seem perspective as they reduce adversely activated neurohumoral factors.

PMID- 10953668
TI  - Cholera, 1999.

PMID- 10953669
TI  - Antimutagenic and some other effects of conjugated linoleic acid.
AB  - Conjugated linoleic acid (CLA) is a collective term for positional and geometric
      isomers of octadecadienoic acid in which the double bonds are conjugated, i.e.
      contiguous. CLA was identified as a component of milk and dairy products over 20
      years ago. It is formed as an intermediate in the course of the conversion of
      linoleic acid to oleic acid in the rumen. The predominant naturally occurring
      isomer is the cis-9, trans-11 modification. Treatment of linoleic acid-rich oils
      such as safflower oil, soybean oil, or maize oil with base and heat will result
      in the formation of CLA. Two isomers predominate in the synthetic preparation,
      c9,t11 and t10,c12. CLA has been shown to inhibit chemically-induced skin,
      stomach, mammary or colon tumours in mice and rats. The inhibition of mammary
      tumours in rats is effective regardless of type of carcinogen or type or amount
      of dietary fat. CLA has also been shown to inhibit cholesterol-induced
      atherosclerosis in rabbits. When young animals (mice, pigs) are placed on CLA
      containing diets after weaning they accumulate more body protein and less fat.
      Since CLA is derived from the milk of ruminant animals and is found primarily in
      their meat and in products derived from their milk there is a concerted world
      wide effort to increase CLA content of milk by dietary means. Its effect on
      growth (less fat, more protein) is also a subject of active research. The
      mechanisms underlying the effects of CLA are still moot.

PMID- 10953670
TI  - Postprandial factor VII metabolism: the effect of the R353Q and 10 bp
      polymorphisms.
AB  - Elevated levels of coagulation factor VII activity (FVIIc) are associated with
      increased risk of CHD. FVIIc is strongly determined by two polymorphisms (R353Q
      and 0/10 base pairs (bp)) and plasma triacylglycerol (TAG) concentrations. The Q
      and 10 bp polymorphisms show strong linkage disequilibrium and have been
      associated with lower levels of fasting FVII, but there has been little
      investigation of the effect of these genotypes on the postprandial FVII
      metabolism. The present study demonstrated that fasting activated factor VII
      (FVIIa) and factor VII antigen (FVIIag) levels were significantly lower in the
      heterozygotes carrying the Q and 10 bp alleles (n 12), than in the R/0 bp
      homozygotes (n 12) (43.0 (SE 4.8) v. 23.9 (SE 6.5) mU/ml and 85.7 (SE 5.4) v.
      71.6 (SE 7.5)% respectively). During postprandial lipaemia there was a
      significant increase in FVIIa in R/0 bp homozygotes but not in the heterozygotes
      carrying the Q and 10 bp alleles. The proportion of FVIIa (FVIIa:FVIIag)
      increased in the homozygotes but not in the heterozygotes (2.04 (SE 0.35) v. 1.20
      (SE 0.26) respectively). Therefore possession of the relatively common Q and 10
      bp alleles is not associated with postprandial activation of FVII, which may in
      turn have a protective effect against CHD.

PMID- 10953671
TI  - The degree of saturation of fatty acids influences post-ingestive satiety.
AB  - Two studies were designed to compare the effects on post-ingestive satiety of
      manipulating the degree of saturation of fatty acids, at a fixed chain length (18
      C atoms), in a fixed energy (5.68 MJ for males; 3.97 MJ for females), high-fat
      (55% energy) lunch meal. Two different groups of twenty subjects (ten males and
      ten females) took part in each study. All forty subjects were of normal weight
      and aged between 18 and 36 years. Study 1 compared the effects of fat A (oleic
      blend, high in monounsaturated fatty acids (MUFA)) with those of fat B (linoleic
      blend, high in polyunsaturated fatty acids (PUFA)) and fat C (stearic-oleic
      blend, high in saturated fatty acids (SFA)). Study 2, which was designed to
      confirm and extend the findings of Study 1, compared the effects of fats A, B and
      C with those of fat D (a linoleic-oleic blend). Energy and nutrient intakes were
      monitored for the rest of the day and for the following day. Profiles of hunger,
      fullness and other sensations were monitored by continuous tracking and end-of
      day questionnaires. In each meal the fat content was exclusively composed of one
      particular type (A, B, C or D) and was divided equally between the main course
      and dessert. Study 1 revealed a significant effect of fat type (degree of
      saturation) on intake of nutrients at the following (dinner) meal (smallest
      F[2,36] 3.38, P < 0.05), on post-ingestive ratings of motivation to eat (smallest
      F[2,36] 4.18, P = 0.02) and on energy intake over the whole test day (F[2,36]
      3.39, P < 0.01). Subjects consumed significantly more energy after consumption of
      the lunch containing fat A than after the lunches containing fats B or C and
      there was a trend for these effects to continue into the second day. In Study 2,
      fat C produced more similar effects on appetite to fat A and there was a tendency
      for subjects to consume more over the whole test day when they had consumed the
      lunch containing fat A than when they had consumed the lunch containing fat B.
      Furthermore, when the data from fat conditions A and B in both studies were
      combined (n 40) the results of Study 1 were confirmed. Overall, the results of
      these short-term studies indicate that PUFA may exert a relatively stronger
      control over appetite than MUFA and SFA.

PMID- 10953673
TI  - Reproducibility of energy and macronutrient intake and related substrate
      oxidation rates in a buffet-type meal.
AB  - The aim of this present study was to determine the reliability of a buffet-type
      meal as a measure of spontaneous energy and macronutrient intake. In addition, we
      evaluated the short-term effects of diet on the composition of the substrate mix
      oxidized postprandially. Fourteen male subjects had ad libitum access to a
      variety of foods from a buffet-type meal offered in the laboratory during two
      identical sessions. The foods comprising the test meal had varying amounts of
      protein, lipid and carbohydrate. The results showed that there were significant
      intraclass correlations (ri) for energy (ri 0.97, P = 0.0001), lipid (ri 0.97, P
      = 0.0001), carbohydrate (ri 0.92, P = 0.0003) and protein (ri 0.82, P = 0.0072)
      intake between the two meal sessions. Hunger and fullness levels measured
      immediately before and during 4 h after the meal were identical under the two
      conditions. In addition, there was no significant difference between the two
      sessions for RQ and resting energy expenditure, which showed significant
      reproducibility for measurements obtained immediately before, immediately after,
      as well as 30 min after, the buffet. This present study demonstrates the high
      reproducibility of energy and macronutrient intake and oxidation rate values
      obtained with a buffet-type meal in healthy male subjects and suggests that the
      use of this test is a reliable method for assessment of macronutrient preferences
      in the laboratory.

PMID- 10953672
TI  - Glycaemic responses to cereal-based Indian food preparations in patients with non
      insulin-dependent diabetes mellitus and normal subjects.
AB  - The in vivo glycaemic responses to six cereal-based foods traditionally consumed
      in South India were evaluated in patients with non-insulin-dependent diabetes
      mellitus (NIDDM) and healthy volunteers. All foods contained 50 g carbohydrate
      and were compared with a 50 g glucose load. Also studied were the in vitro starch
      digestibility and nutrient composition of the foods. The postprandial responses
      to the foods at 30, 60 and 120 min were significantly (P < 0.05) lower than those
      to the reference glucose, in both groups. The peak glucose responses for three
      foods, i.e. chapatti, idli and poori, occurred 60 min postprandially in both
      groups. The glycaemic index (GI) values ranged from 67 to 90 in NIDDM and from 44
      to 69 in healthy subjects with no significant differences within the groups.
      Significant relationships were observed between peak responses and area under the
      curve for foods in patients with NIDDM and in vitro rate of starch hydrolysis (r
      0.83, r 0.85, P < 0.05). The GI values predicted using in vitro data were found
      to be similar to the GI values observed in patients with NIDDM. The GI concept is
      useful for identifying foods in the habitual Indian diet with attributes of the
      desired glycaemic effect such as delayed peak rise and low area under the curve.

PMID- 10953674
TI  - Energy expenditure on household, childcare and occupational activities of women
      from urban poor households.
AB  - This present study attempts to measure the energy cost of activities of women
      from the poor socio-economic group in India. Women in the age group of 18-40
      years (n 98) either working for incomes or classified as homemakers were randomly
      selected. Time disposition studies were conducted by a 24 h observation of their
      activities on a typical day. Predominant activities were identified from the
      activity profiles and standardized for posture and duration. The BMR (Douglas bag
      method) and energy cost of the activities (Kofranyi-Michaelis meter) were
      measured by indirect calorimetry. The energy consumption during these activities
      ranged from 2.94-12.51 kJ/min. The tasks were divided into standard, household,
      childcare, occupational and other activities. Using the World Health
      Organization/Food and Agriculture Organization/United Nations University (1985)
      criteria, attempts were made to categorize the activities into light, moderate
      and heavy. It was significant that except for walking, the standard activities
      and occupational work could be classified into the light category (< 2.2 BMR).
      Most of the household and childcare activities except cooking were classified
      into the moderate to heavy (2.2-> 2.8 BMR). The energy expenditure of activities
      did not differ significantly between women with different occupations. This
      present study provides an important database on energy costs of activities for
      computing energy requirements of women involved in similar activity patterns.

PMID- 10953675
TI  - The transfer of 15N from urea to lysine in the human infant.
AB  - To explore the nutritional significance of urea hydrolysis for human subjects,
      male infants being treated for severe undernutrition were given oral doses of 10
      mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after
      repletion with either moderate or generous intakes of protein. Urea hydrolysis
      was calculated from the 15N enrichment of urinary urea, and where possible,
      lysine, alanine, glycine and histidine were isolated from urine by preparative
      ion-exchange chromatography for measurement of 15N enrichment. Sufficient N was
      obtained for 15N enrichment of lysine to be measured on fifteen occasions from
      six children. Urea hydrolysis accounted for half of all urea production with 130
      (SD 85) mg N/kg hydrolysed per d, most of which appeared to be utilized in
      synthetic pathways. Of the samples analysed successfully, nine samples of lysine
      were enriched with 15N (mean atom percent excess 0.0102, range 0.0017-0.0208)
      with relative enrichment ratios with respect to lysine of 1.63 (range 0.18-3.15),
      1.96 (range 0.7-3.73) and 0.9 (range 0.4-1.8) for glycine, alanine and histidine
      respectively. Enriched samples were identified at each treatment phase and 68% of
      the variation in lysine enrichment was explained by the variation in urea
      enrichment with 54% explained by the overall rate of delivery of 15N to the lower
      gastrointestinal tract. The results indicate a minimum of 4.7 mg lysine per kg
      body weight made available by de novo synthesis with the more likely value an
      order of magnitude higher. Thus, urea hydrolysis can improve the quality of the
      dietary protein supply by enabling an increased supply of lysine and other
      indispensable amino acids.

PMID- 10953676
TI  - Use of the retinol-binding protein: transthyretin ratio for assessment of vitamin
      A status during the acute-phase response.
AB  - The ratio plasma retinol-binding protein (RBP):transthyretin (TTR) has been
      proposed as a means to improve the assessment of vitamin A status of individuals
      with concurrent infection or inflammation. We have measured RBP and TTR in stored
      sera from South African children who had accidentally ingested kerosene. Samples
      were collected from these children in hospital when suffering acute inflammation
      and respiratory distress, and from them and neighbourhood control children 3
      months later. Vitamin A status was defined by modified relative dose response
      (MRDR) tests of liver retinol stores at 3 months and by serum retinol
      concentration both when children were ill and when they were well. Illness was
      defined as either being in hospital or, at follow-up, as having a raised plasma
      alpha 1-acid glycoprotein (AGP) level. The RBP:TTR value was significantly
      decreased by both illness and low liver retinol stores. When the effects on
      RBP:TTR of illness and vitamin A stores were considered together for the 3-month
      follow-up samples, only vitamin A status significantly decreased the value. We
      calculated sensitivity and specificity of the RBP:TTR ratio against established
      measures of vitamin A status using a cut-off value of 0.3 for RBP:TTR and
      standard cut-off values for MRDR (0.06) and plasma retinol (0.7 mumol/l).
      Compared with MRDR, RBP:TTR had sensitivities of 76% and 43% and specificities of
      22% and 81% to detect vitamin A deficiency in hospitalized and well children
      respectively. Compared with plasma retinol, sensitivities were 88% and 44% and
      specificities were 55% and 64% in hospitalized and well children respectively.
      Only for the case of clinically well children with biochemical evidence of
      subclinical inflammation did sensitivity (62% and 100% against MRDR and plasma
      retinol respectively) and specificity (100% and 60% against MRDR and retinol)
      approach useful levels for an assessment tool. Overall, although a trend
      supporting the theory behind the use of the RBP:TTR for assessment of vitamin A
      status in infection was observed in the current study, the ratio did not provide
      adequate sensitivity and specificity to be a useful assessment tool.

PMID- 10953677
TI  - Effect of composition of ruminally-infused short-chain fatty acids on net fluxes
      of nutrients across portal-drained viscera in underfed ewes.
AB  - Four ewes, each fitted with a rumen cannula and with catheters in the mesenteric
      artery and portal and mesenteric veins, received continuous intrarumen infusions
      of water or of short-chain fatty acids (SCFA). SCFA infusions were isoenergetic
      (83 kJ/h) and provided rumen molar proportions (acetate:propionate:butyrate) of
      70:20:10, 50:40:10 or 50:20:30. The rumen SCFA production rate with the basal
      diet was 90.0, 23.1 and 8.8 mmol/h for acetate, propionate and butyrate
      respectively. Portal net fluxes indicated that 74, 67 and 22-30% of infused
      acetate, propionate and butyrate respectively, reached the portal vein. Portal
      net release of beta-hydroxybutyrate increased with SCFA infusions, irrespective
      of the amount of butyrate infused. Portal net release of lactate decreased with
      high-butyrate infusion. Portal net uptake of glucose increased with the SCFA
      infusions. In ewes infused with water, a portal net uptake of total amino acids
      (AA) was observed. SCFA infusions decreased the uptake of nonessential AA
      (glutamate, glycine, but not glutamine) and increased the net release of tyrosine
      and essential AA (isoleucine, leucine). Portal net fluxes of AA were similar with
      both high-acetate and high-propionate infusions. Lower net uptake of glutamine
      and net release of most essential AA and some nonessential AA were observed with
      the high-butyrate infusion. Energetic summation of portal net release was not
      significantly different between the three SCFA infusions, although it tended to
      be lower with high-butyrate infusion. This may be related to the higher trophic
      effect of butyrate on the digestive mucosa.

PMID- 10953678
TI  - Effect of viscosity on digestion of nutrients in conventional and germ-free
      chicks.
AB  - A study was conducted with conventional and germ-free broiler chicks to obtain
      more information on the role of the intestinal microflora in the anti-nutritive
      effects of NSP in broiler chicks. As the NSP source, highly methylated citrus
      pectin (HMC) was used at a dose level of 30 g/kg in a maize-based diet. The diets
      fed to the germ-free chicks were gamma-irradiated, whereas those fed to the
      conventional chicks were not. Feeding the HMC diet to conventional birds
      depressed weight gain and food utilization (P < 0.05), whereas in germ-free birds
      only weight gain was reduced (P < 0.05). Feeding the HMC diet to conventional
      birds reduced digestibilities of energy and starch at the end of the jejunum.
      Ileal digestibilities of starch and energy were not strongly affected when birds
      were fed on the HMC-containing diet. Faecal digestibilities of organic matter,
      crude fat, starch and amino acids, N retention and metabolizable energy were
      reduced when conventional chicks were fed on the HMC diet. Feeding the HMC diet
      to germ-free birds hardly affected faecal digestibility of nutrients and N
      retention, whereas metabolizable energy was increased. Feeding the HMC diet to
      conventional or germ-free birds increased the viscosity of the digesta in the
      small intestine. This increase in digesta viscosity was more pronounced in
      conventional than in germ-free birds. The pH of ileal digesta was reduced when
      HMC was added to the diet of conventional chicks, but not in germ-free chicks.
      Feeding the HMC diet to conventional birds markedly affected morphology of the
      gut wall, whereas in germ-free chicks very little effect was found on gut
      morphology. Based on the results of the present study, it is concluded that the
      gastrointestinal microflora mediates the magnitude of the anti-nutritive effects
      of HMC in broiler chicks. However, the exact role of the microflora in chicks in
      the magnitude of the anti-nutritional effects of HMC could not be derived from
      the present study, since the results might have been influenced by gamma
      irradiation of the diets fed to the germ-free chicks.

PMID- 10953679
TI  - Consumption of olive oil has opposite effects on plasma total cholesterol and
      sphingomyelin concentrations in rats.
AB  - The hypothesis that olive-oil consumption alters plasma sphingomyelin
      concentrations and hepatic sphingomyelin metabolism was tested. Rats were fed on
      purified, high-cholesterol diets with either coconut fat or olive-oil (180 g/kg).
      In accordance with previous work, olive-oil v. coconut-fat consumption
      significantly elevated hepatic and total plasma cholesterol concentrations.
      During the course of the experiment, the concentration of plasma sphingomyelin
      rose in the coconut-fat group and remained constant in the olive-oil group. When
      compared with the coconut-fat-fed group, the plasma sphingomyelin levels were
      significantly lower in the olive-oil-fed group after 14 and 21 d of treatment.
      Dietary olive oil raised the amounts of cholesterol and sphingomyelin in the VLDL
      density region, and this change was associated with a reduction in the
      cholesterol and sphingomyelin contents of the LDL and HDL density ranges. Olive
      oil consumption reduced the activity of serine palmitoyltransferase, while the
      activities of phosphatidylcholine:ceramide cholinephosphotransferase and
      phosphatidylethanolamine:ceramide ethanolaminephosphotransferase were left
      unchanged. Dietary olive oil also enhanced the activity of acidic
      sphingomyelinase, but not that of neutral sphingomyelinase. The present data
      indicate that dietary olive oil v. coconut fat has opposite effects on total
      plasma cholesterol and sphingomyelin concentrations. The lower plasma
      sphingomyelin levels observed in olive-oil-fed, as compared with coconut-fat-fed
      rats, may be explained by a simultaneous elevation and reduction in sphingomyelin
      catabolism and synthesis respectively, as based on the measured enzyme
      activities.

PMID- 10953680
TI  - Chronically gorging v. nibbling fat and cholesterol increases postprandial
      lipaemia and atheroma deposition in the New Zealand white rabbit.
AB  - In the present study, we compared the effects of nibbling and gorging on
      postprandial lipaemia and lipoproteins, hepatic lipid uptake and atheroma
      deposition. New Zealand White rabbits were fed on a low-fat (LF) control diet or
      a peanut oil- (10 g/d) and cholesterol- (0.5 g/d) enriched (HF) diet with the fat
      and cholesterol components given either by nibbling (HF-N) or gorging (HF-G).
      After 4 and 8 weeks, rabbits were given a test meal, which was either nibbled or
      taken as a bolus. The LF diet did not noticeably alter postprantial lipid
      variables. Triacylglycerol levels, 0-35 h lipid responses and plasma accumulation
      of dietary lipids were significantly higher in the HF-G group than in the HF-N
      group, despite higher post-heparin plasma lipase activities. Furthermore, as
      studied on cultured isolated hepatocytes, the higher the rate of supply of
      triacylglycerol- and cholesterol-rich lipoproteins (TCRL), the lower the rate of
      lipid uptake and bile salt secretion. Atheroma deposition was significantly
      increased by gorging the HF diet and was correlated with levels of most
      postprandial lipid variables. We conclude that gorging v. nibbling a fat and
      cholesterol-enriched diet exacerbates postprandial lipaemia by reducing the rate
      of TCRL clearance and favours atheroma deposition.

PMID- 10953681
TI  - Response of diamine oxidase and other plasma copper biomarkers to various dietary
      copper intakes in the rat and evaluation of copper absorption with a stable
      isotope.
AB  - There is a lack of agreement on index of Cu status and reliable and sensitive
      biomarkers are still required. The purpose of this present work was to assess in
      rats the sensitivity of diamine oxidase (DAO) activity, a recently proposed
      biomarker, to modifications in dietary Cu intake in comparison with other plasma
      biomarkers of Cu status. We also evaluated the effect of Cu dietary level on Cu
      and Zn intestinal absorption. Results showed that plasma Cu and plasma
      caeruloplasmin were significantly decreased at day 8 compared with the control
      group (7.4 mg Cu/kg diet) while DAO activity was significantly decreased at day
      12 of the deficient diet (0.61 mg Cu/kg diet). Cu supplementation (35 mg Cu/kg
      diet) had no effect on any of the studied biomarkers of Cu status. In Cu
      deficient rats plasma Cu and DAO activities were normalized 4 d after return to
      the control diet while caeruloplasmin was normalized later, at day 11. Apparent
      absorption values (%) of total Cu or 65Cu isotope were significantly increased in
      the Cu-deficient rats compared with the other groups and similar in the control
      and the Cu-supplemented groups. The urinary excretion of total Cu or 65Cu isotope
      were increased in the Cu-supplemented group compared with the other two groups.
      Both apparent absorption and urinary excretion of total Zn or 67Zn isotope
      remained unchanged in the three experimental groups. In conclusion, DAO activity
      seemed to be less sensitive to Cu deficiency than plasma Cu or caeruloplasmin
      concentrations. The present study also showed a significant increase in Cu
      intestinal absorption with dietary Cu restriction but no decrease with Cu
      supplementation in the rat.

PMID- 10953682
TI  - Seymour Kety. In memory of the father of neuroscience and biological psychiatry.

PMID- 10953683
TI  - Exfoliative erythroderma. Skin biopsy is required to determine the cause of this
      pruritic eruption.

PMID- 10953684
TI  - Ventricular arrhythmias. Preventing sudden death with drugs and ICD devices.
AB  - Sudden cardiac death occurs most frequently in persons age 50 to 60, and serious
      ventricular arrhythmias are the cause of death in most cases. The underlying
      substrate is usually CAD, either a healed infarction or an acute ischemic event.
      Early studies using antiarrhythmic drugs to improve post-MI survival led instead
      to increased mortality, casting doubt on this approach. A cascade of studies
      using newer antiarrhythmic drugs showed some promise in selected patients post
      MI. Another approach--using implantable defibrillators--may show greater benefit
      than antiarrhythmic drugs in patients at serious risk, but the widespread
      implantation of these devices may be cost-prohibitive. Management of serious
      ventricular arrhythmias is guided by the individual patient's comorbidities,
      cardiac function, history of ischemia, and perceived risk of sudden death.

PMID- 10953685
TI  - Anti-aging medicine. Partners put evolutionary theory into practice. Interview by
      Alice V. Luddington.

PMID- 10953686
TI  - Lipid levels. Applying the second National Cholesterol Education Program report
      to geriatric medicine.
AB  - Aging is accompanied by increases in cholesterol levels that increase the risk of
      atherosclerosis, coronary heart disease, and stroke. A large body of evidence
      shows that lipid lowering can reduce the incidence of vascular-related events.
      Guidelines for the management of hypercholesterolemia were outlined in the second
      National Cholesterol Education Program report (Adult Treatment Panel II).
      According to ATPII, the first step is to identify individuals at risk for
      vascular disease and those with borderline-high or high cholesterol levels.
      Screening for hyperlipidemia should continue beyond age 65 if the individual
      patient would benefit from long-term lipid management. Primary and secondary
      interventions consist of dietary therapy, exercise, and pharmacotherapy, based on
      the individual patient's risk factors.

PMID- 10953687
TI  - Competency assessments. A case for the nursing interventions classification and
      the observation of daily work.

PMID- 10953688
TI  - What is leadership?

PMID- 10953689
TI  - Patient documentation.

PMID- 10953690
TI  - Charting by exception.

PMID- 10953691
TI  - Hospital use of nursing personnel: holding steady through the 1990s.

PMID- 10953692
TI  - Job satisfaction and nurses in rural Australia.

PMID- 10953693
TI  - Improving managers' critical thinking skills: student-generated case studies.

PMID- 10953694
TI  - Knowledge, skills, and attributes needed for nurse and non-nurse executives.

PMID- 10953695
TI  - Transforming negative work cultures: a practical strategy.
AB  - At a time of unprecedented turbulence and challenge for healthcare organizations,
      maintaining healthy work environments is of paramount importance. Such
      environments support the day-to-day work of an organization and link its mission
      to customer service strategies and goals. We describe an unhealthy work culture
      and outline a practical approach that healthcare managers and clinical leaders
      can use to facilitate and sustain cultural transformation. The model is built on
      the core principles of ownership and investment in service outcomes as well as
      the life of the organization.

PMID- 10953696
TI  - Developing a nursing management practice atlas: Part 1, Methodological approaches
      to ensure data consistency.
AB  - Challenges associated with the use of secondary data sources for benchmarking in
      nursing administration research are identified. A methodological approach for
      ensuring data consistency is presented in part one of this two-part series. Part
      two (September 2000) will provide an analysis of the nursing management data,
      based on a set of nursing and financial resource benchmarking variables
      identified by the senior nurse executives of these sites. Initial findings show
      evidence of data consistency across similar hospitals.

PMID- 10953697
TI  - Relationships between nurse executives and physicians: the gender paradox in
      healthcare.
AB  - Findings from a study about the perspectives of women nurse executives in a
      heavily managed care environment revealed that physicians were perceived as
      extremely powerful and that the nurse executive-physician relationship was not as
      collaborative as would be expected. Findings suggest that gender socialization
      processes, played out in nurse-physician interactions, contribute to the gender
      paradox in healthcare leadership.

PMID- 10953698
TI  - Relationship-centered care: achieving true value in healthcare.
AB  - Intuitively, most healthcare leaders and caregivers appreciate the significance
      of effective relationships and their probable connection with positive patient
      outcome and financial success. In light of the lack of empirical descriptions and
      support for these relationships, however, a reluctance is seen to ascribe
      significant value, energy, and financial resources to relationship building. We
      describe the national initiative sponsored by the Fetzer Institute to support the
      Relationship-Centered Care Network, describe a relationship model to gain a
      greater appreciation of the complexities of relationships, and share experiences
      of an organization that operates based on the principles of relationship-centered
      care.

PMID- 10953699
TI  - The fragmentation of community: Part 1, The loss of belonging and commitment at
      work.
AB  - Squeezed between mounting budget pressures and staffing demands, healthcare
      managers have little room to maneuver as they are buffeted by incessant new
      strategies. So what is the constant that they can use to keep a steady course
      through all the chaos? We suggest the overarching constant is "community in the
      workplace." Although it may have both short- and long-term benefits, community
      building is not a strategy but a career-long philosophy, structure, and approach
      to help managers tie together all the facets of their daily work into a more
      meaningful and satisfying purpose. This article, part 1 in a 4-part series,
      describes the negative dynamics found in many healthcare organizations that often
      result in the inability to get past short-term strategies and tactics to achieve
      long-term, sustainable change. It highlights why managers might decide to make
      the philosophical shift away from the mechanistic views of the past to build
      community and free up resources and talents of the organization in an entirely
      new way. Part 2 (September 2000) will explore the principles and characteristics
      of "community" and provide material for further study and discussion. Part 3
      (October 2000) describes how to build community as well as options for
      implementing change in complex adaptive systems. The final article (November
      2000) presents case studies and how "community" can be built in a unionized
      environment.

PMID- 10953700
TI  - California licensing bill polarizes veterinary community.

PMID- 10953701
TI  - Lawmakers mull over minor use/minor species bill.

PMID- 10953702
TI  - Radiation therapy for unresectable thyroid carcinomas.

PMID- 10953703
TI  - Reservations about detomidine-ketamine combination.

PMID- 10953704
TI  - Case made for preconditioning programs for feeder cattle.

PMID- 10953705
TI  - Error in dosage for phenobarbital.

PMID- 10953706
TI  - Women in veterinary medicine.

PMID- 10953707
TI  - What is your diagnosis? Soft tissue opacity in stomach and duodenum.

PMID- 10953708
TI  - Continuing education needs assessment for on-farm food safety services.
AB  - OBJECTIVE: To identify the perceived market or client demand for dairy on-farm
      food safety services by veterinarians, the need for a food safety continuing
      education program, and the educational issues that might be addressed in an on
      farm food safety curriculum. DESIGN: Survey. STUDY POPULATION: Consulting dairy
      veterinarians, government veterinarians located in California, and meat packers
      slaughtering cull dairy cows in California. PROCEDURE: Results of a questionnaire
      supplied to veterinarians and telephone interviews with meat packer
      representatives were analyzed by use of univariate and multivariate logistic
      regression procedures. RESULTS: Some meat packers considered the quality of
      incoming cull dairy cattle as a control point for food safety hazards. More than
      50% of dairy and government-employed veterinarians believed that a current market
      for on-farm food safety services exists; > 85% believed that a potential market
      exists. Duration since graduation was negatively correlated with belief in a
      current market. Government-employed veterinarians were more likely to believe in
      a current market. Veterinarians were more likely to express a strong interest in
      offering on-farm food safety services if they believed a current market exists,
      indicated that they already offer such services, or listed residues and pathogens
      as the most important issues facing the dairy industry. CONCLUSIONS AND CLINICAL
      RELEVANCE: Although a potential market for on-farm food safety services is
      perceived, veterinarians are unsure of their role in this area. new demands of
      meat packers slaughtering cull dairy cows may be the motivation practitioners
      need to broach the subject of food safety with clients.

PMID- 10953709
TI  - Rebreathing anesthetic systems in small animal practice.

PMID- 10953710
TI  - Nonrebreathing anesthetic systems in small animal practice.

PMID- 10953711
TI  - Role of neutrophils in intestinal mucosal injury.

PMID- 10953712
TI  - Effect of dietary protein content and tryptophan supplementation on dominance
      aggression, territorial aggression, and hyperactivity in dogs.
AB  - OBJECTIVE: To evaluate the effect of high- and low-protein diets with or without
      tryptophan supplementation on behavior of dogs with dominance aggression,
      territorial aggression, and hyperactivity. DESIGN: Prospective crossover study.
      ANIMALS: 11 dogs with dominance aggression, 11 dogs with territorial aggression,
      and 11 dogs with hyperactivity. PROCEDURE: In each group, 4 diets were fed for 1
      weeks each in random order with a transition period of not < 3 days between each
      diet. Two diets had low protein content (approximately 18%), and 2 diets had high
      protein content (approximately 30%). Two of the diets (1 low-protein and 1 high
      protein) were supplemented with tryptophan. Owners scored their dog's behavior
      daily by use of customized behavioral score sheets. Mean weekly values of 5
      behavioral measures and serum concentrations of serotonin and tryptophan were
      determined at the end of each dietary period. RESULTS: For dominance aggression,
      behavioral scores were highest in dogs fed unsupplemented high-protein rations.
      For territorial aggression, [corrected] tryptophan-supplemented low-protein diets
      were associated with significantly lower behavioral scores than low-protein diets
      without tryptophan supplements. CONCLUSIONS AND CLINICAL RELEVANCE: For dogs with
      dominance aggression, the addition of tryptophan to high-protein diets or change
      to a low-protein diet may reduce aggression. For dogs with territorial
      aggression, tryptophan supplementation of a low-protein diet may be helpful in
      reducing aggression.

PMID- 10953715
TI  - Patient and environmental factors associated with calcium oxalate urolithiasis in
      dogs.
AB  - OBJECTIVE: To test the hypothesis that breed, age, sex, body condition, and
      environment are risk factors for development of calcium oxalate uroliths in dogs.
      DESIGN: Case-control study. ANIMALS: 1,074 dogs that formed calcium oxalate
      uroliths and 1,724 control dogs that did not have uroliths. PROCEDURE: A
      validated multiple-choice questionnaire was designed to collect information from
      veterinarians and owners within 1 year of the date of urolith detection
      concerning signalment and environment of the dogs. Univariate and multivariate
      analyses were performed to calculate odds ratios to assess whether breed, age,
      sex, body condition, and environment were risk factors for calcium oxalate
      urolith formation. RESULTS: Middle-aged (8- to 12-year-old) castrated male dogs
      had increased risk for formation of calcium oxalate uroliths. Urolith formation
      was also associated with increasing age. Dogs of certain breeds, including
      Miniature and Standard Schnauzer, Lhasa Apso, Yorkshire Terrier, Bichon Frise,
      Shih Tzu, and Miniature and Toy Poodle, had increased risk for developing calcium
      oxalate uroliths. Overweight dogs also had increased risk. CONCLUSIONS AND
      CLINICAL RELEVANCE: Knowledge of patient and environmental risk factors for
      development of calcium oxalate uroliths may facilitate development of
      surveillance strategies that result in earlier detection of this disease.
      Modification of environmental factors and body weight may minimize calcium
      oxalate urolith formation and recurrence.

PMID- 10953714
TI  - Cardiorespiratory responses and plasma cortisol concentrations in dogs treated
      with medetomidine before undergoing ovariohysterectomy.
AB  - OBJECTIVE: To evaluate effects of medetomidine on anesthetic dose requirements,
      cardiorespiratory variables, plasma cortisol concentrations, and behavioral pain
      scores in dogs undergoing ovariohysterectomy. DESIGN: Randomized, prospective
      study. ANIMALS: 12 healthy Walker-type hound dogs. PROCEDURE: Dogs received
      medetomidine (40 micrograms/kg [18.2 micrograms/lb] of body weight, i.m.; n = 6)
      or saline (0.9% NaCl) solution (1 ml, i.m.; 6) prior to anesthesia induction with
      thiopental; thiopental dose needed for endotracheal intubation was compared
      between groups. Ovariohysterectomy was performed during halothane anesthesia.
      Blood samples were obtained at various times before drug administration until 300
      minutes after extubation. Various physiologic measurements and end-tidal
      halothane concentrations were recorded. RESULTS: In medetomidine-treated dogs,
      heart rate was significantly lower than in controls, and blood pressure did not
      change significantly from baseline. Plasma cortisol concentrations did not
      increase significantly until 60 minutes after extubation in medetomidine-treated
      dogs, whereas values in control dogs were increased from time of surgery until
      the end of the recording period. Control dogs had higher pain scores than treated
      dogs from extubation until the end of the recording period. CONCLUSION AND
      CLINICAL RELEVANCE: Administration of medetomidine reduced dose requirements for
      thiopental and halothane and provided postoperative analgesia up to 90 minutes
      after extubation. Dogs undergoing ovariohysterectomy by use of thiopental
      induction and halothane anesthesia benefit from analgesia induced by medetomidine
      administered prior to anesthesia induction. Additional analgesia is appropriate
      60 minutes after extubation.

PMID- 10953717
TI  - Coronavirus-associated epizootic catarrhal enteritis in ferrets.
AB  - OBJECTIVE: To characterize clinical signs and lesions and identify the etiologic
      agent associated with epizootic catarrhal enteritis in domestic ferrets. DESIGN:
      Cross-sectional study. ANIMALS: 119 ferrets with epizootic diarrhea of presumed
      viral cause and 5 control ferrets. PROCEDURE: Clinical records and biopsy or
      necropsy specimens of ferrets with presumed epizootic catarrhal enteritis were
      reviewed. Immunohistochemical staining for coronavirus antigen was performed on
      paraffin-embedded tissues from approximately 10% of affected ferrets to identify
      viral antigen and determine its distribution. Transmission electron microscopy
      was performed on fecal samples and sections of jejunum. Virus isolation studies
      as well as immunofluorescent tests for other similar viruses were performed.
      RESULTS: Characteristic microscopic lesions consistent with intestinal
      coronavirus infection (vacuolar degeneration and necrosis of villus enterocytes;
      villus atrophy, fusion, and blunting; and lymphocytic enteritis) were
      consistently detected in affected ferrets. Coronavirus particles were identified
      in feces and jejunal enterocytes by use of transmission electron microscopy.
      Immunohistochemical staining of jejunal sections revealed coronavirus antigens.
      Antigen staining was not detected in healthy ferrets or ferrets with other
      gastrointestinal tract diseases. Virus isolation was unsuccessful, and other
      similar viruses were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      strongly implicate a coronavirus as the causative agent of epizootic catarrhal
      enteritis in ferrets. Diagnosis may be made on the basis of a combination of
      historical, clinical, and microscopic findings.

PMID- 10953716
TI  - Association between patient-related factors and risk of calcium oxalate and
      magnesium ammonium phosphate urolithiasis in cats.
AB  - OBJECTIVE: To determine whether breed, age, sex, or reproductive status (i.e.,
      neutered versus sexually intact) was associated with the apparent increase in
      prevalence of calcium oxalate (CaOx) uroliths and the decrease in prevalence of
      magnesium ammonium phosphate (MAP) uroliths in cats over time. DESIGN: Case
      control study. ANIMALS: Case cats consisted of cats with CaOx (n = 7,895) or MAP
      (7,334) uroliths evaluated at the Minnesota Urolith Center between 1981 and 1997.
      Control cats consisted of cats without urinary tract disease admitted to
      veterinary teaching hospitals in the United States and Canada during the same
      period (150,482). PROCEDURE: Univariate and multivariate logistic regression were
      performed. RESULTS: British Shorthair, Exotic Shorthair, Foreign Shorthair,
      Havana Brown, Himalayan, Persian, Ragdoll, and Scottish Fold cats had an
      increased risk of developing CaOx uroliths, as did male cats and neutered cats.
      Chartreux, domestic shorthair, Foreign Shorthair, Himalayan, Oriental Shorthair,
      and Ragdoll cats had an increased risk of developing MAP uroliths, as did female
      cats and neutered cats. Cats with CaOx uroliths were significantly older than
      cats with MAP uroliths. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      changes in breed, age, sex, or reproductive status did not contribute to the
      apparent reciprocal relationship between prevalences of CaOx and MAP uroliths in
      cats during a 17-year period. However, cats of particular breeds, ages, sex, and
      reproductive status had an increased risk of developing CaOx and MAP uroliths.

PMID- 10953718
TI  - Severe sepsis in cats: 29 cases (1986-1998).
AB  - OBJECTIVE: To document the clinical, clinicopathologic, and pathologic findings
      in cats with severe sepsis, identify abnormalities unique to this species, and
      identify criteria that could be used antemortem to diagnose the systemic
      inflammatory response syndrome in cats. DESIGN: Retrospective study. ANIMALS: 29
      cats confirmed to have severe sepsis at necropsy. PROCEDURE: Pertinent history,
      physical examination findings, and results of hematologic and biochemical testing
      were extracted from medical records. RESULTS: Clinical diagnoses included
      pyothorax, septic peritonitis, bacteremia secondary to gastrointestinal tract
      disease, pneumonia, endocarditis, pyelonephritis, osteomyelitis, pyometra, and
      bite wounds. Physical examination findings included lethargy, pale mucous
      membranes, poor pulse quality, tachypnea, hypo- or hyperthermia, signs of diffuse
      pain on abdominal palpation, bradycardia, and icterus. Clinicopathologic
      abnormalities included anemia, thrombocytopenia, band neutrophilia,
      hypoalbuminemia, low serum alkaline phosphatase activity, and hyperbilirubinemia.
      Necropsy findings included multi-organ necrosis or inflammation with
      intralesional bacteria. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      severe sepsis in cats is characterized by lethargy, pale mucous membranes, signs
      of diffuse abdominal pain, tachypnea, bradycardia, weak pulses, anemia,
      hypoalbuminemia, hypothermia, and icterus. Recognition of this combination of
      clinical findings should facilitate the diagnosis of severe sepsis in cats.

PMID- 10953719
TI  - Reactivity to intradermal injection of extracts of Dermatophagoides farinae,
      Dermatophagoides pteronyssinus, house dust mite mix, and house dust in dogs
      suspected to have atopic dermatitis: 115 cases (1996-1998).
AB  - OBJECTIVE: To compare reactivities to intradermal injection of extracts of
      Dermatophagoides farinae, Dermatophagoides pteronyssinus, house dust mite mix,
      and house dust in dogs suspected to have atopic dermatitis. DESIGN: Retrospective
      study. ANIMALS: 115 dogs. PROCEDURES: Records of all dogs suspected to have
      atopic dermatitis that underwent intradermal testing between October 1996 and
      July 1998 were reviewed. Reactivities to intradermal injection of crude mixed
      house dust mite (1:25,000 wt/vol) and crude house dust (25 PNU/ml) extracts were
      compared with reactivities to intradermal injection of individual extracts of D
      farinae and D pteronyssinus (1:50,000 wt/vol). RESULTS: Ninety dogs were
      confirmed to have atopic dermatitis including 61 of the 69 dogs with positive
      reactions to either or both of the individual house dust mite extracts.
      Intradermal testing with the mixed house dust mite extract had sensitivity of
      75%, specificity of 96%, and accuracy of 83%. Intradermal testing with the house
      dust extract had sensitivity of 30%, specificity of 93%, and accuracy of 56%.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of crude mixed house
      dust mite and crude house dust extracts for intradermal testing in dogs is not as
      accurate a method of determining house dust mite hypersensitivity as is the use
      of individual D farinae and D pteronyssinus extracts mainly because of the high
      percentage of false-negative results. Extracts of individual house dust mites are
      recommended for intradermal testing of dogs suspected to have atopic dermatitis.

PMID- 10953720
TI  - Association between measures of milk quality and risk of violative antimicrobial
      residues in grade-A raw milk.
AB  - OBJECTIVE: To determine whether bulk-tank standard plate counts or plate loop
      counts and bulk-tank somatic cell counts (SCC) were associated with detection of
      violative antimicrobial residues in milk from dairy cattle. DESIGN: Longitudinal
      study. PROCEDURE: Information for 1994 through 1997 was obtained from a large
      milk marketing cooperative that operated in multiple states throughout the
      northeastern and midwestern United States (16,831 herd-years of information from
      6,546 farms) and from the Ohio Department of Agriculture Grade-A Milk
      Certification Program (12,042 herd-years of information from 4,022 farms). Data
      were analyzed by use of multivariate logistic regression. RESULTS: For both data
      sets, odds that a violative antibiotic residue would be detected increased as
      mean SCC for the herd-year increased. Standard plate counts and plate loop counts
      were not associated with odds that a violative antibiotic residue would be
      detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested
      that the odds that a violative antibiotic residue would be found in bulk-tank
      milk increased as mean SCC for the herd-year increased. This suggests that
      management practices that would be expected to influence SCC may also influence
      the risk of antibiotic residue violations.

PMID- 10953721
TI  - Use of orally administered carfentanil prior to isoflurane-induced anesthesia in
      a Kodiak brown bear.
AB  - A captive 590-kg (1,298-lb) 22-year-old castrated male Kodiak brown bear was
      evaluated because of a soft tissue mass in the right carpal and antebrachial
      regions. General anesthesia was deemed necessary on 3 occasions for various
      procedures including radiographic evaluation and biopsy, excision, and radiation
      treatment. The bear was given carfentanil orally to induce sedation, followed by
      i.m. administration of tiletamine-zolazepam (on 1 occasion) and atropine.
      Anesthesia was maintained by administration of isoflurane in oxygen. After each
      procedure, effects of carfentanil were reversed by administration of naltrexone.
      Although there was some variability, blood pressure, nasal temperature, heart
      rate, respiratory rate, oxygen saturation, PO2, and PCO2 remained within a
      clinically acceptable ranges.

PMID- 10953722
TI  - [3rd Vienna International Geriatric Congress. Vienna, Austria, 4-5 May 2000.
      Abstracts].

PMID- 10953723
TI  - Left ventricular filling in young patients affected by insulin-dependent diabetes
      mellitus: a stress Doppler echocardiography study.
AB  - BACKGROUND: The purpose of this study was to analyze diastolic function in two
      different populations of young patients affected by insulin dependent diabetes
      mellitus (IDDM), with and without systemic diabetic complications, and to compare
      the results obtained at rest with those obtained during isometric exercise.
      METHODS: Forty-five IDDM diabetic patients were studied. On the basis of presence
      or absence of systemic diabetic complications (nephropathy and retinopathy)
      patients were divided into two groups. Group I (20 patients) without and Group II
      (25 patients) with diabetic complications. Diastolic function parameters were
      measured by Doppler echocardiography at rest and during isometric exercise. The
      two groups were similar regarding age, metabolic control and insulin dosage but
      there were significant differences in diastolic and systolic blood pressure and
      heart rate between the two groups, the patients with complications showing higher
      values (p < 0.001, p < 0.005, p < 0.01 respectively). RESULTS: Group II already
      presented at rest alterations of diastolic function parameters respect to Group I
      with a marked increase of: peak velocity of late left ventricular filling (peakA
      cm/sec), (60.1 +/- 13.4 versus 48.4 +/- 8.9, p < 0.01); late left ventricular
      filling integral (A area), (6.5 +/- 1.4 versus 5.0 +/- 0.8, p < 0.05); late left
      ventricular filling integral over total filling (A area/total area), (0.31 +/-
      0.06 versus 0.26 +/- 0.06, p < 0.01). There was a decrease of E/A ratio in Group
      II versus Group I (1.5 +/- 0.32 versus 1.9 +/- 0.5, p < 0.05). During isometric
      exercise these changes became even more pronounced in patients with complications
      and in this group there was a marked decrease of flow integral of early left
      ventricular filling over total filling (E area/total area), (0.57 +/- 0.09 versus
      0.68 +/- 0.07, p < 0.01). CONCLUSIONS: In conclusion, young IDDM patients with
      complications show an impairment of diastolic function more pronounced than those
      without. These changes are more evident during isometric exercise. Stress Doppler
      echocardiography is a reliable tool to detect early diastolic dysfunction in
      diabetic patients.

PMID- 10953724
TI  - Treatment of hypopituitarism in infancy. Effect on head circumference growth.
AB  - BACKGROUND: Head circumference of children with multiple pituitary-hormone
      deficiency (MPHD) may be subnormal for age. Moreover it is known that linear
      growth in infancy is growth-hormone (GH) dependent. Therefore, aim of the study
      has been to compare head circumference measurements in children with
      hypopituitarism after L-thyroxine (L-T4) therapy alone, before therapy with GH,
      and after GH was added to the therapy. METHODS: Five infants (2 girls, 3 boys)
      with MPHD, diagnosed and treated before the age of 2 years and whose auxological
      parameters records during L-T4 therapy alone were available, were retrospectively
      studied. Head circumference and length measurements were expressed as standard
      deviation score (SDS). Weight measurements were expressed as weight for length
      ratio percentage. RESULTS: Initially treated with L-T4 alone for a mean period of
      4, 5 months, there were neither positive effects on head circumference nor on
      linear growth. A significant catch-up growth was observed only employing GH
      therapy in addition to L-T4: mean head circumference SDS and length SDS increased
      respectively from -2.20 to -0.89 SDS and from -4.16 to -0.87 SDS after a mean
      period of 18 months of combined GH and L-T4 therapy. CONCLUSIONS: Therefore, head
      circumference growth, in infancy, is growth hormone dependent as well as linear
      growth, and during GH treatment, monitoring head circumference growth is
      important as much as monitoring linear growth.

PMID- 10953726
TI  - Stability of serum TSH concentration after non refrigerated storage.
AB  - BACKGROUND: The ignorance of how sensitive serum samples for defined assays may
      be, can lead to overprotecting measures. This attitude not only increases cost
      and labor in everyday routine but may be responsible for not evaluating series of
      measurements if performed in serum samples not well stored. METHODS: Thyrotropin
      (TSH) concentration in serum was tested in three pooled samples drawn from
      various patients, before and after four days storage at freezing (-15 degrees C),
      low (4 degrees C), and room temperature (18-22 degrees C). TSH concentration was
      measured in each part, in 22 replicates using a commercial assay. RESULTS: The
      variation of the measured values due to the storage conditions was less than 10%,
      not exceeding the accepted between assay variation. CONCLUSIONS: For the
      estimation of TSH concentration, patient serum samples may be stored up to four
      days at 4 degrees C or even at room temperature without significant loss of
      measurement accuracy.

PMID- 10953725
TI  - GH response to GHRH combined with pyridostigmine or arginine in different
      conditions of low somatotrope secretion in adulthood: obesity and Cushing's
      syndrome in comparison with hypopituitarism.
AB  - BACKGROUND: Diagnosing GH deficiency in adults is difficult due to the age
      related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH
      replacement is allowed for patients with GH peak to provocative stimuli < 3
      micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in
      obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is
      difficult due to variations of GH and IGF-I levels as function of age and
      nutrition status. METHODS: We aimed to verify the GH response to GHRH (1 mg/kg
      i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg
      i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women
      with Cushing's syndrome (CS), and in 72 control subjects (NS). RESULTS: IGF-I
      levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which,
      in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to
      GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5
      mg/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always
      below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L;
      conventionally, below this limit severe GH deficiency is shown and rhGH
      replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were
      similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD,
      respectively. Six out of 11 OB had GH peaks below the normal limits but nobody <
      3 micrograms/L. In CS, the GH response to GHRH + PD was lower than that to GHRH +
      ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and
      even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had
      GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively
      while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG +
      GHRH. CONCLUSIONS: Present data demonstrate that the maximal somatotrope
      secretory capacity is reduced in OB and even more in CS. From a diagnostic point
      of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As
      hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG +
      GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope
      secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the
      maximal somatotrope secretory capacity is sometimes so reduced as to overlap with
      that of severe GHD.

PMID- 10953727
TI  - Nitrite plasma levels in type 1 and 2 diabetics with and without complications.
AB  - BACKGROUND: The authors thought it interesting to examine the interrelationship
      between nitric oxide and diabetes mellitus by the determination of the nitrite
      plasma levels, stable end-products of nitric oxide, in various clinical patterns
      of diabetes mellitus. METHODS: Our series consisted of 161 female subjects (mean
      age 54 +/- 7 years, disease duration 5 +/- 3 months) subdivided into: a) 13
      patients suffering from insulin-dependent diabetes (IDDM) without clinical and
      instrumental signs of micro- and macroangiopathy; b) 148 suffering from non
      insulin-dependent diabetes mellitus (NIDDM) of whom: 1) 52 without vascular
      complications (28 normal weight, BMI < 25, and 24 obese, BMI > 30); 2) 40 with
      clinical and instrumental signs of non hypertensive coronary heart disease (CHD);
      3) 25 with CHD and hypertension (arterial blood pressure over 160/95 mmHg); 4) 31
      with hypercholesterolemia (values over 250 mg/dl). All patients were examined in
      good glycometabolic conditions reached by oral hypoglycemiant (12 cases) or
      insulin (149 cases) treatment. As normal control 37 female subjects (mean age 48
      +/- 7) without internistic diseases were considered. For each sample we
      determined the plasma levels of nitrites by the Gutman and Hollywood method.
      RESULTS: Almost similar nitrite plasma levels in IDDM (17 +/- 0.5 mumol/L) and
      normal controls (17 +/- 0.2 mumol/L) were found; in non complicated non obese
      NIDDM a not significantly elevated value (21 +/- 0.8 mumol/L) as compared with
      the IDDM and control group was found; the obese NIDDM patients showed a value (18
      +/- 0.4 mumol/L) not significantly different in comparison with the non obese
      NIDDM group. In the NIDDM group with non hypertensive CHD) the nitrite value was
      almost similar (20 +/- 0.5 mumol/L) to the corresponding group without vascular
      complications. In the patients with CHD and hypertension the nitrite level was
      superimposable (20 +/- 0.7 mumol/L) on the one recorded in NIDDM patients without
      vascular complications and in those with CHD without hypertension. In NIDDM
      patients with hypercholesterolemia the mean nitrite value was sharply elevated
      (24 +/- 0.8 mumol/L); the difference between this group and those of non
      hypercholesterolemic, non obese, obese and CHD (with or without hypertension)
      patients was significant (p < 0.05). CONCLUSIONS: It is conceivable that diabetes
      mellitus per se causes a tendential not significant increase of NO production in
      comparison with normal controls; some factors such as blood pressure, overweight,
      disease duration, therapeutic treatment and coronary complications appear not to
      influence NO production. In hypercholesterolemic diabetic patients the nitrite
      enhanced level in plasma might mean a compensatory response to a continuous
      inactivation of NO involved in a protective competition towards damaging factors
      and chiefly against oxidised LDL.

PMID- 10953728
TI  - Acromegaly and intestinal neoplasms.
AB  - Acromegalic subjects show increased frequency of neoplastic lesions in the colon
      and rectum with respect to the general population. Recent prospective studies
      using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and
      up to 4 time increased presence of colorectal cancer in acromegaly, independently
      of sex, age, duration of disease and clinical status of the patients. The polyps
      are distributed throughout the extension of the large bowel and are often
      multiple, showing at least two different histologic types: hyperplastic and
      adenomatous. Sometimes they are associated with intestinal carcinomas.
      Pancolonoscopy is the procedure of choice for the diagnosis of large bowel
      neoplasms, even though it may be difficult to complete in these subjects because
      of the frequent presence of an enlarged and elongated colon. It shows a higher
      sensitivity and specificity compared to other tests such as the barium enema,
      fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore,
      it is recommended to follow up acromegalic patients using pancolonoscopy to
      obtain early detection of neoplastic lesions in the large bowel.

PMID- 10953729
TI  - Diagnosis and treatment of hypercortisolism in children.

PMID- 10953730
TI  - Neuroendocrine tumors of the gastroenteric canal. Anatomopathological and
      diagnostic-therapeutic definition. Description of a case with a rare cecal
      localisation.
AB  - The authors take the case of a neuroendocrine tumour of the cecum as the starting
      point for an analysis of the anatomopathological and diagnostic-therapeutic
      aspects of these neoplasms. Furthermore, the authors underline that
      neuroendocrine tumours (NET) of the colon represent an extremely rare nosological
      entity and that they are heterogeneous from a clinical and biochemical point of
      view, thus making a reliable preoperative diagnosis a problem that is still
      difficult to resolve today.

PMID- 10953731
TI  - Unusual cases of endocarditis.

PMID- 10953732
TI  - Managing disputes within medicine: is there a role for alternative dispute
      resolution?

PMID- 10953733
TI  - HIV resistance testing: value for money.

PMID- 10953734
TI  - The molecular genetics of human herpesvirus 8.
AB  - Epidemiological evidence from the early 1990s suggested that a sexually
      transmitted infectious agent other than the HIV virus was associated with the
      development of Kaposi's sarcoma in patients with HIV. A novel gamma herpesvirus
      was identified in Kaposi's sarcoma lesions. The molecular genetics of this virus
      are reviewed in this article.

PMID- 10953735
TI  - HIV, childbirth and suicidal behaviour: a review.
AB  - Women who are both pregnant and HIV positive may be at particularly high risk of
      suicidal behaviour. This is important in view of recent guidelines recommending
      routine antenatal HIV testing. We present a case and review the relevant
      literature.

PMID- 10953736
TI  - Preventing perinatal transmission of HIV-1 infection.
AB  - It is now known that with the use of antiretroviral prophylaxis with zidovudine,
      elective caesarean section delivery and refraining from breastfeeding the rate of
      mother-child transmission of HIV infection can be reduced to less than 2%.

PMID- 10953737
TI  - Neurological manifestations of malignant disease.
AB  - Neurological complications of cancer are some of the most feared manifestations
      of malignant disease. Their frequency is increasing with improvements in the
      treatment of primary systemic disease. This article discusses the approach to
      patients with neurological complications of cancer and reviews some of the most
      common causes.

PMID- 10953738
TI  - Clinical governance in action: radiology.
AB  - Articles and conferences on clinical governance abound, but much of the content
      is theoretical. This article describes how clinical governance may be introduced
      in a busy radiology department in a straightforward and practical way, with
      benefits to both the radiologist and patient.

PMID- 10953739
TI  - Snoring: recent developments.
AB  - Despite limited evidence validating its efficacy, surgery to overcome snoring is
      commonly undertaken. This article looks at the development of snoring surgery to
      present day, highlighting its limitations and outlining current methods being
      used to target the surgery more effectively.

PMID- 10953740
TI  - Radical cystectomy and bladder substitution.
AB  - The incidence of bladder cancer is rising. The main treatment for superficial
      bladder cancer is local resection and judicious use of intravesical agents.
      Radical cystectomy can cure organ-confined, invasive disease. The ileal conduit
      remains the gold standard following cystectomy. Newer methods of bladder
      substitution and nerve-sparing techniques have resulted in better tolerance of
      this treatment.

PMID- 10953741
TI  - Effective transition from paediatric to adult services.
AB  - The effective transfer of adolescents from paediatric to adult services is a new
      quality issue confronting all health services. This article reviews current
      knowledge in the field and outlines good practice.

PMID- 10953742
TI  - Leflunomide: a new DMARD for rheumatoid arthritis.
AB  - Early diagnosis and referral of rheumatoid arthritis may significantly improve
      patient outcomes. Arava (leflunomide) is the first new disease modifying
      antirheumatic drug (DMARD) to be introduced in the UK for over a decade. Arava
      has a rapid onset of action and has been shown to retard radiographic disease
      progression and significantly improve patients' functional ability.

PMID- 10953743
TI  - Responding to trainee doctors in difficulty.
AB  - Appropriate workload, good clinical and educational supervision and rigorous
      appraisal routines will prevent a number of trainees developing difficulties.
      When difficulties do occur the presence of such arrangements will facilitate
      appropriate emotional and practical handling of these problems.

PMID- 10953744
TI  - Educational supervision for PRHOs: getting it right?
AB  - The New Doctor highlights aspects of educational supervision for preregistration
      house officers that may serve as a lesson for improving the educational
      experience of all doctors in training. On the basis of research carried out in
      mid-Trent, this article highlights some of the issues relating to the training of
      educational supervisors and how these need to be put into context if further
      advances in education and training are to take place.

PMID- 10953745
TI  - Atopic eczema and staphylococcal endocarditis: time to recognize an association?

PMID- 10953746
TI  - An unusual case of enterococcal tricuspid valve endocarditis.

PMID- 10953747
TI  - Branch retinal artery occlusion: a case complicating acute rheumatic fever and
      dental abscess.

PMID- 10953748
TI  - Giant diverticulum of colon treated by diverticulectomy.

PMID- 10953749
TI  - Albumin and meningococcal disease.

PMID- 10953750
TI  - Thrombolysis in pulmonary embolism.

PMID- 10953751
TI  - A case of intraoperative pyrexia.

PMID- 10953752
TI  - Antioxidant status in children with juvenile rheumatoid arthritis (JRA) living in
      Cairo, Egypt.
AB  - The aim of this study was to examine both enzymatic and non-enzymatic antioxidant
      status in a select group of children with juvenile rheumatoid arthritis (JRA),
      living in Cairo, Egypt. The plasma concentrations of albumin, ceruloplasmin,
      vitamin C, vitamin E as well as erythrocyte superoxide dismutase and whole blood
      glutathione peroxidase activities were all significantly decreased in the
      presence of JRA compared to those without JRA. Unlike these antioxidant factors,
      vitamin A and its carrier (e.g. retinol binding protein), which have very little
      or no antioxidant property, remained unaffected by JRA. These results suggest
      that the children with JRA are subject to oxidative stress.

PMID- 10953753
TI  - Food-related behaviors during drought: a study of rural Fulani, northeastern
      Nigeria.
AB  - Two rural settled Fulani villages in northeast Nigeria were surveyed for dietary
      practices and use of edible wild plants (n = 100 adult subjects). Dietary
      patterns and medical data were obtained for children under 5, pregnant and
      lactating women and the elderly. A diversified diet was maintained at both
      geographical locations through hunting, gathering, agriculture, horticulture,
      animal husbandry, food exchanges and cash purchases. Edible wild plants
      associated with children included fruits of baure (Ficus sycomorus), faru (Lannea
      schiniperi), giginya (Gardenia aqualla), kokiya (Strychnos spinosa) and nunu
      (Parinari curatellitolia). Leaves of shiwaka (Veronia colorate) were consumed by
      lactating women to stimulate breastmilk production. Generally, fruits of baure
      (Ficus sycomorus) were eaten to counter stomach pain; fruits of kisni (Bridelia
      ferruginea) were eaten to treat diarrhea; and bark of kuka (Adansonia digitata)
      was consumed for weight gain. Food storage was more important during wet seasons
      than dry because of local and regional flooding. Adult Fulani men rode to distant
      markets on bicycles, while women walked to market and in some instances expended
      3200 kcal/day engaging in this activity.

PMID- 10953754
TI  - Nutritional and hematological impact of dietary flaxseed and defatted flaxseed
      meal in rats.
AB  - An 8-week study was conducted to determine the impact of dietary ground flaxseed
      (FS) or defatted flaxseed meal (FLM) on plasma lipids, minerals, hematological
      parameters and vitamin E status of weanling female Sprague-Dawley rats. These
      rats were fed isocaloric modified AIN-76 diets supplemented with 0.0, 5.0, 10.0%
      (w/w) FS or 6.2% (w/w) FLM for 56 days. Total and HDL cholesterol were not
      influenced by any of the dietary treatments. Plasma triglyceride was
      significantly increased by FLM, but not affected by FS. Total RBC counts and
      hematocrit were significantly higher in FS groups than in the control group;
      however, hemoglobin was not affected by FS. Dietary FLM had no effect on any of
      the above hematological parameters. Plasma alkaline phosphatase, an indicator of
      Zn status and a marker of bone formation, was significantly lower in the FS and
      FLM groups than in the control group. Plasma vitamin E content was not influenced
      by dietary treatment. Liver vitamin E was significantly higher in groups fed 10%
      FS and 6.2% FLM. In summary, moderate amounts of dietary FS may have the
      potential to increase liver vitamin E level and improve iron status. However,
      FS/FLM consumption may have a negative effect on zinc status, as indicated by
      decreased alkaline phosphatase levels.

PMID- 10953755
TI  - Short-term satiety in preschool children: a comparison between high protein meal
      and a high complex carbohydrate meal.
AB  - The aim of this study was to investigate whether a high protein meal has a
      different effect on short-term satiety in preschool children than a high
      carbohydrate meal by measuring their intake of a subsequent meal. Subjects were
      35 normal preschool children of both genders aged 5 to 6 years. All children were
      healthy and randomly chosen from those who were attending to a day-care center
      where they received feeding at three meal times: breakfast, lunch and teatime.
      Children were weighed with light clothes following standard recommendations. They
      were normal according to the weight for height index, using the NCHS standards.
      Two meals with different levels of protein and carbohydrate and equal energy
      contents were assayed at lunch. The lunches were cooked dishes made from common
      ingredients. The high carbohydrate meal was consumed in greater amount than the
      high protein meal (P < 0.01) and a significantly greater energy intake was
      observed (P < 0.01). Food and energy intakes at teatime were greater with the
      high carbohydrate meal, but only the energy intake was significant (P < 0.05).
      When subjects consumed the high protein meal during lunch, they ate a
      significantly lower amount of protein in the subsequent meal, but the
      carbohydrate intake was similar. The long-term effects of a high protein diet
      remain to be investigated before recommending of a high protein for obese
      children.

PMID- 10953756
TI  - Some behavioural changes observed among fasting subjects, their nutritional
      habits and energy expenditure in Ramadan.
AB  - This study was conducted in five provinces and food consumption, physical
      activity types and duration for 3 consecutive days were recorded in the
      questionnaire together with some general characteristics of 750 (320 males, 430
      females) adults who were on fast during Ramadan at time of interview. One hundred
      and eighty-seven subjects had some type of health problems, among whom 60.4% were
      using drugs, and 31.6% were on diets; however, during Ramadan 9.7 and 18.8% of
      the subjects dropped taking drugs and did not regularly keep on diets,
      respectively. During the fasting time, from dawn to sunset, 34.3% of the subjects
      developed some behavioural disturbances, such as feeling tired and being
      unwilling to work. Although the meal consumed at dawn consisted of foods that
      were usually eaten at breakfast, the meal consumed at sunset consisted of a great
      variety of foods. Calcium intake was the most insufficiently consumed nutrient.
      It was observed that the daily energy intakes were less than the expenditures
      both in males and females. Further research should be done on the effects of
      fasting in health and disease.

PMID- 10953758
TI  - Wundt versus Galton--two approaches to gathering psychophysical measurements.

PMID- 10953757
TI  - Traditional alcoholic beverages of Tanzania: production, quality and changes in
      quality attributes during storage.
AB  - Traditional alcoholic beverages of Tanzania play an important role in the daily
      social, economic, nutritional and cultural life of the people. Production,
      quality and changes in quality attributes during ambient temperature storage were
      investigated in traditional Tanzanian beers (Mbege and Komoni) and wines
      (Mnanasi, Wanzuki and Mofru). The quality attributes of the alcoholic beverages
      indicated that pH levels were in the range of 4.15-4.20 and 3.9-5.5 for the beers
      and wines respectively. Total, fixed and volatile acidity in the beers were in
      the range of 0.41-0.62, 0.28-0.38 and 0.06-0.09 g/100 mL respectively while in
      the wines acidity levels were in the range of 0.23-0.66, 0.13-0.33 and 0.05-0.06
      g/100 mL for the total, fixed and volatile acidity respectively. Concentration of
      total solids in the beers ranged between 7.00 and 12.80 degrees Brix while in the
      wines ranged between 3.45 and 6.65 degrees Brix. Specific gravity of the beers
      ranged between 1.0097 and 1.0374 while for wines the specific gravity was lower,
      ranging between 0.9971 and 0.9989. Alcohol concentration was higher in wines
      (range 3.84-9.75 g/100 mL) than in beers (range 1.72-2.76 g/100 mL). Storage of
      the beverages under ambient temperatures for various lengths of time resulted in
      significant (P < 0.05) increase in total acidity, volatile acidity and alcohol
      content and decrease in the total solids and specific gravity. Mbege and Komoni
      beers indicated the highest rates of deterioration with total acid production
      rates of 0.3774 g/100 mL and 0.0914 g/100 mL per hour respectively. Wines were
      more stable during storage than beers, with Mofru wine being the most stable. The
      rates of total acid production per hour were Mnanasi (0.0196 g/100 mL), Wanzuki
      (0.0047 g/100 mL) and Mofru (0.0005 g/100 mL). Use of low brewing technologies
      involving uncontrolled fermentation, unsanitary conditions and use of rudimentary
      equipment for processing, packaging and storage resulted in beers and wines of
      low quality and short shelf-life. To foster commercial exploitation of the
      products, there is a need to develop appropriate small and medium-level brewing
      technologies that will improve the quality of the traditional alcoholic beverages
      and extend their shelf-life through hygienic and controlled processing,
      packaging, and storage.

PMID- 10953759
TI  - Invariant recognition of natural objects in the presence of shadows.
AB  - Shadows are frequently present when we recognize natural objects, but it is
      unclear whether they help or hinder recognition. Shadows could improve
      recognition by providing information about illumination and 3-D surface shape, or
      impair recognition by introducing spurious contours that are confused with object
      boundaries. In three experiments, we explored the effect of shadows on
      recognition of natural objects. The stimuli were digitized photographs of fruits
      and vegetables displayed with or without shadows. In experiment 1, we evaluated
      the effects of shadows, color, and image resolution on naming latency and
      accuracy. Performance was not affected by the presence of shadows, even for gray
      scale, blurry images, where shadows are difficult to identify. In experiment 2,
      we explored recognition of two-tone images of the same objects. In these images,
      shadow edges are difficult to distinguish from object and surface edges because
      all edges are defined by a luminance boundary. Shadows impaired performance, but
      only in the early trials. In experiment 3, we examined whether shadows have a
      stronger impact when exposure time is limited, allowing little time for
      processing shadows; no effect of shadows was found. These studies show that
      recognition of natural objects is highly invariant to the complex luminance
      patterns caused by shadows.

PMID- 10953760
TI  - Cavanagh and Leclerc shape-from-shadow pictures: do line versions fail because of
      the polarity of the regions or the contour?
AB  - Shape-from-shadow perception fails when the contour bordering a shadowed area is
      reduced to a black line, and the shadow area becomes white. It might be that the
      polarity of the shadowed and illuminated areas has to be from dark on the
      shadowed side to light on the illuminated side for successful perception. Or it
      may be that the line, which has two contours, has one too many for shape-from
      shadow processing. Alternatively, the problem might be that one of the contours
      of the line is incorrectly polarised. To test these explanations, three shape
      from-shadow figures were prepared, each depicting the same referent--an elderly
      person. All three figures had two correctly polarised areas. One figure had a
      correctly polarised contour at the border between the areas. One had two
      correctly polarised contours. The other had one correctly polarised contour and
      one incorrectly polarised contour. The referent of the figure with one
      incorrectly polarised contour was the one difficult to make out. The result has
      implications for several theories, including an account of a demonstration by
      Hering involving penumbra.

PMID- 10953761
TI  - The role of surface attraction in perceiving volumetric shape.
AB  - Rock [1973, Orientation and Form (New York: Academic Press)] showed that form
      perception generally depends more on the orientation of a stimulus in world
      coordinates than on its orientation in retinal coordinates. He suggested that the
      assignment of an object's 'environmental orientation' depends on gravity, visual
      frame of reference, and the observer's ability to impose orientation along one
      axis or another. This paper shows that the assignment of environmental
      orientation and perceived 3-D form also depends on the relationship between an
      object and retinally adjacent surfaces in the scene to which it might be
      attached. Whereas previous examples have demonstrated effects of orientation on 2
      D form, we show that orientation can affect the perceived intrinsic 3-D shape of
      a volume.

PMID- 10953762
TI  - Transformation of the visual-line value in binocular vision: stimuli on
      corresponding points can be seen in two different directions.
AB  - We examined Wheatstone's (1838 Philosophical Transactions of the Royal Society of
      London 128 371-394) claim that images falling on retinally corresponding points
      can be seen in two different directions, in violation of Hering's law of
      identical visual direction. Our analyses showed that random-dot stereograms
      contain stimulus elements that are conceptually equivalent to the line stimuli in
      the stereogram from which Wheatstone made his claim. Our experiment demonstrated
      that two lines embedded in a random-dot stereogram appeared in two different
      directions when they stimulated retinally corresponding points, if the disparity
      gradient value of the lines was infinity relative to adjacent elements. To ensure
      that the two lines stimulated corresponding points, observers made vergence eye
      movements while maintaining the perception of the two lines in two different
      directions.

PMID- 10953763
TI  - When texture takes precedence over motion in depth perception.
AB  - Both texture and motion can be strong cues to depth, and estimating slant from
      texture cues can be considered analogous to calculating slant from motion
      parallax (Malik and Rosenholtz 1994, report UCB/CSD 93/775, University of
      California, Berkeley, CA). A series of experiments was conducted to determine the
      relative weight of texture and motion cues in the perception of planar-surface
      slant when both texture and motion convey similar information. Stimuli were
      monocularly viewed images of planar surfaces slanted in depth, defined by texture
      and motion information that could be varied independently. Slant discrimination
      biases and thresholds were measured by a method of single-stimuli binary-choice
      procedure. When the motion and texture cues depicted surfaces of identical
      slants, it was found that the depth-from-motion information neither reduced slant
      discrimination thresholds, nor altered slant discrimination bias, compared to
      texture cues presented alone. When there was a difference in the slant depicted
      by motion and by texture, perceived slant was determined almost entirely by the
      texture cue. The regularity of the texture pattern did not affect this weighting.
      Results are discussed in terms of models of cue combination and previous results
      with different types of texture and motion information.

PMID- 10953764
TI  - Apparent swinging motion from a 2-D sinusoidal pattern.
AB  - A new motion illusion is reported that is observed on a 2-D sinusoidal pattern
      composed of two 1-D sinusoids, in which the constituent elements of the middle
      column appear to swing relative to the two flanking columns when the point of
      fixation is slowly moved back and forth about the middle column. To better
      understand the underlying mechanisms of the apparent swinging motion, the spatial
      properties of a 2-D sinusoidal pattern were examined in terms of spatial
      frequency, orientation, and contrast. Thirty-four subjects rated the magnitude of
      the motion. The apparent swinging was greatest when the two 1-D components had
      spatial frequencies of 1-2 cycles deg-1, relative orientations between 15 degrees
      and 30 degrees, and high contrasts. A spatiotemporal interaction between
      spatially overlapping visual units differing in polarity (Khang and Essock, 1997
      Perception 26 585-597, 831-846) and the resultant shift in the global-motion
      signal was proposed as a likely cause of the apparent swinging motion.

PMID- 10953765
TI  - Cholinergic agents and the McCollough effect.
AB  - The strength of the McCollough effect (ME), a pattern-contingent colour
      aftereffect, has been shown to be inversely related to acetylcholine, being
      significantly strengthened by (anticholinergic) scopolamine and weakened by
      (cholinergic) physostigmine delivered before adapting to the ME stimuli. The
      purpose of the present study was (i) to establish whether the effect of pre
      adaptation scopolamine is linearly dose-dependent and (ii) to investigate the
      effects of scopolamine and physostigmine delivered between adaptation and
      testing. In experiment 1, ten healthy male volunteers who received placebo, or
      0.6 mg, 1.2 mg, or 1.8 mg scopolamine before adapting to ME stimuli showed a
      significant linear dose-dependence over tests repeated from 10 to 70 min after
      adaptation. In experiment 2 twelve male volunteers adapted to ME stimuli and then
      received placebo, 1.2 mg oral scopolamine, or 0.75 mg subcutaneous physostigmine.
      On subsequent repeated testing, strength of the ME was increased by scopolamine
      and decreased by physostigmine relative to placebo. Both experiments were double
      blind double-dummy repeated measures. These data support the view that the ME is
      a product of inhibitory mechanisms in the visual system rather than processes
      involved in associative learning.

PMID- 10953766
TI  - Vertical and bisection bias in active touch.
AB  - We investigated the conditions that underlie the vertical and bisection illusion
      in touch, in order to understand the basis of their similarity to visual
      illusions, and the means of reducing the biases in length perception by active
      touch. Movement, speed, and spatial reference cues were tested. Movements in
      scanning L-shapes in ipsilateral and contralateral (across the body midline)
      table-top space produced significant underestimation of the vertical line with
      the right hand, but not with the left hand. Right-handed scanning of L-shapes
      showed no significant bias when the vertical line in the figure was aligned to
      the body midline, suggesting that spatial cues were involved. The vertical line
      was overestimated in inverted T-shapes, but underestimated in rotated T-shapes,
      implicating line bisection. Holding scanning latencies constant reduced the
      vertical error for inverted T-shapes, but could not explain the bisection bias.
      Sectioning biases were predicted by the location of junctions on sectioned lines,
      showing that junction points act as misleading anchor cues for movement extents.
      The illusion was significantly reduced when reference information was added by
      instructing subjects to relate two-handed scanning of the figure to an external
      frame and to body-centred cues. It is argued that disparities in spatial
      reference (anchor) cues for movement extents are involved in vertical and
      bisection biases in active touch. The hypothesis that length illusions depend on
      disparities in spatial reference information can also account for the similarity
      of the tactile to the visual horizontal-vertical illusion.

PMID- 10953767
TI  - The changing face of law and medicine in the new millennium. Foreword.

PMID- 10953768
TI  - Medicine in the new millennium: a self-help guide for the perplexed.

PMID- 10953769
TI  - Applying fiduciary responsibilities in the managed care context.

PMID- 10953770
TI  - The globalization of health law: the case of permissibility of placebo-based
      research.

PMID- 10953771
TI  - Tobacco litigation: smoke, mirrors and public policy.

PMID- 10953772
TI  - Health care in Hawaii: an agenda for research and reform.

PMID- 10953773
TI  - Medicare's future: fact, fiction and folly.

PMID- 10953774
TI  - Regulating medical practice in the cyber age: issues and challenges for state
      medical boards.

PMID- 10953775
TI  - Health care reform in the year 2000: the view from the front of the classroom.

PMID- 10953776
TI  - Alternative medicine's roadmap to mainstream.

PMID- 10953777
TI  - Parenting among mothers with a serious mental illness.
AB  - In the past few decades, deinstitutionalization and community-based
      rehabilitation and support programs have increased the likelihood that women with
      serious mental disorders will be parents and will raise their children. This
      review describes what is known about the parenting of these women, focusing on
      diagnosis, child characteristics, and other contextual effects.

PMID- 10953778
TI  - Childhood experiences of abuse, later substance use, and parenting outcomes among
      low-income mothers.
AB  - Relationships among childhood abuse, subsequent adult functioning (with a focus
      on severity of substance abuse), and child placement were explored in an urban
      sample of low-income, African-American mothers. Childhood sexual trauma and age
      were found to be correlated with severity of later drug use; history of physical
      or sexual abuse was significantly related to psychological distress in adulthood;
      and addiction was highly correlated with child placement. Implications of the
      findings are discussed, with particular reference to collaborations between child
      welfare and substance abuse treatment.

PMID- 10953779
TI  - Children's emotional and behavioral disorders: attributions of parental
      responsibility by professionals.
AB  - In the wake of the neurobiological "revolution," do mental health professionals
      still assign etiological responsibility for emotional and behavioral disorders to
      deficient or harmful parenting? This study investigated differences in
      attributions of causality by theoretical orientation, professional discipline,
      areas of practice, familiarity with parent support groups, and demographic
      characteristics. Implications for policy, research, and practice are discussed.

PMID- 10953780
TI  - Attachment to transitional objects: role of maternal personality and mother
      toddler interaction.
AB  - The origins of soft-object attachments were explored in terms of maternal
      personality and child temperament as measured by maternal questionnaires and by
      laboratory observation of child temperament and mother-toddler interactions.
      Toddlers' soft-object attachments were found to be predicted by the maternal
      variables of constraint and positive affectivity, the latter in combination with
      low child activity level.

PMID- 10953781
TI  - Patterns of children's coping with life stress: implications for clinicians.
AB  - In a study of children's patterns of coping with daily stressors, boys and girls
      9-17 years old were asked to complete a coping checklist in response to one of
      four types of stressors--school, parents/family, siblings, or peer/interpersonal.
      Patterns of coping-strategy use were found to be similar across the various
      stressors, with wishful thinking, problem-solving, and emotional regulation being
      among those most frequently used. Older adolescents, compared to younger
      children, tended to use a broader range of coping strategies, regardless of
      stressor. Implications for clinical practice are discussed.

PMID- 10953782
TI  - Psychiatric disorders in adolescents exposed to domestic violence and physical
      abuse.
AB  - The relationship between abuse and psychiatric diagnoses was investigated in two
      groups of physically abused adolescents, 57 living in homes with interparental
      violence and 32 in homes without such violence, and in 96 nonabused adolescents
      living in nonviolent homes. Adolescents in the first group were found to be at
      greater risk for depression, separation anxiety disorder, post-traumatic stress
      disorder, and oppositional defiant disorder than were those in the second group.
      Adolescents in the first group also appeared more vulnerable to anxiety and
      depression.

PMID- 10953783
TI  - Gender differences in young adolescents' exposure to violence and rates of PTSD
      symptomatology.
AB  - Gender differences in exposure to violence and levels of PTSD symptomatology were
      examined in a school-based sample of 621 young adolescents. Also investigated as
      predictors of PTSD symptoms were cognitive coping strategies, perceived social
      support, and the affective experience of fear. Results support the importance of
      evaluating gender differences, differentiating between violence by type and
      location, and considering both cognitive and affective factors as predictors of
      PTSD symptomatology.

PMID- 10953784
TI  - Assessment of a new rehabilitative coping skills module for persons with
      schizophrenia.
AB  - A rehabilitative coping skills module employing problem solving and cognitive
      behavioral therapy and an experimental repeated-measure design was tested on 55
      randomly selected persons severely handicapped by schizophrenia, most of whom had
      lived almost half of their lives in psychiatric wards. Unlike the control group
      of 44 comparable schizophrenics, the experimental group exhibited a significant
      decrease in delusions and increase in self-esteem, and maintained hygiene levels.

PMID- 10953786
TI  - The Neighborhood Club: a supportive intervention group for children exposed to
      urban violence.
AB  - This paper describes a short-term, supportive intervention group, the
      "Neighborhood Club," designed to assist children with the psychological impact of
      exposure to urban violence. It addresses the void of therapeutic work attending
      to poor children's chronic exposure to community violence. Theoretical and
      clinical rationales for this intervention are discussed, and illustrations from
      ten school-based groups are offered.

PMID- 10953785
TI  - Effectiveness of specialized treatment programs for veterans with serious and
      persistent mental illness: a three-year follow-up.
AB  - This is the first study to test concurrently the effectiveness of four treatment
      programs for patients with serious mental illness. Three-year outcome data on
      utilization and functioning demonstrated important positive changes for seriously
      mentally ill veterans enrolled in specialized, enhanced inpatient and community
      case management treatment programs, when compared to patients in an enhanced day
      treatment program or traditional standard care.

PMID- 10953787
TI  - Psychological adjustment in adult adoptees: assessment of distress, depression,
      and anger.
AB  - Psychological adjustment was assessed in a sample of 525 female and 191 male
      adoptees. Analyses were conducted by gender; by search status, i.e., those who
      had never searched, those who were searching, and those who had made contact with
      their biological parents; and by history of mental health service utilization.
      Compared to normative data, the sample reported significantly higher levels of
      psychological maladjustment; only women adoptees scored higher on a scale
      measuring anger. Overall, adoptees' scores were elevated but did not approach
      levels typical of outpatient populations.

PMID- 10953788
TI  - [Giant hydronephrosis. Diagnostic aspect: report of a case].
AB  - In this study, we have reported an unusual case of giant hydronephrosis of the
      right kidney diagnosed as a result of pain, and upon palpation the detection of
      an abdominal mass. An ultrasound examination also indicated the possible presence
      of a large abdominal liquid mass. The hydatic serology was negative. A
      complementary CT scan and retroperitoneal approach confirmed the diagnosis of a
      right giant hydronephrosis with a liquid content of 8 liters, caused by stricture
      at the pyeloureteral junction with destruction of the kidney. The liquid was
      drained off. Based on the findings in this case, the pathogenesis, diagnosis and
      investigation of giant hydronephrosis have been discussed. In the event of giant
      hydronephrosis with total destruction of the kidney following an anomaly at the
      pyeloureteral junction, nephrectomy has to be performed. In the presence of a
      retroperitoneal liquid mass and in the absence of other pathological signs, the
      diagnosis of a possible giant hydronephrosis should be taken into consideration.

PMID- 10953789
TI  - [Spontaneous perirenal urinoma during nephritic colic].
AB  - A case has been reported of the spontaneous rupture of the kidney during an
      attack of nephritic colic. This rare complication is due to excessive pressure in
      the renal cavities caused by an obstructive ureteral calculus. Complete
      resolution of the urinoma was obtained after endoscopic fragmentation of the
      calculus and double J stenting.

PMID- 10953790
TI  - [Emphysematous pyelonephritis: a case report].
AB  - In this study, a case of emphysematous pyelonephritis has been reported in a 70
      year old diabetic male with a non-functional contralateral kidney. In spite of
      appropriate medical treatment and surgical drainage, the outcome was negative.
      The case in question concerned a rare form of the disease, i.e., emphysematous
      pyelonephritis, a severe and necrotizing infection which is characterized by the
      presence of intraparenchymal gas produced by anaerobic bacteria, and the rapid
      development of acute sepsis or septic shock. Medical treatment alone is seldom
      sufficient, and surgical intervention, in most instances consisting of radical
      nephrectomy rather than surgical drainage, is advocated due to the extent of the
      necrotic lesions.

PMID- 10953791
TI  - [Pyonephrosis: diagnosis and treatment: report of 14 cases].
AB  - Prior to the introduction of antibiotics, the treatment of pyelonephrosis
      frequently consisted of nephrectomy to remove the non-functional kidney, which
      was a potentially dangerous source of systemic infection. This approach was later
      modified as a result of the advances made in antibiotic therapy, and included
      vigorous antibiotic treatment and prompt drainage of the kidney. At present,
      percutaneous nephrostomy provides a means of draining off the pus and determining
      a possible residual renal function. In this study, 14 cases of pyonephrosis were
      observed over a 7-month period. Lumbar pain was noted in 70% of cases, painful
      lumbar contact in 5 cases and fever, shivering and pyuria in all cases.
      Cytobacteriological urine analysis showed the presence of Escherichia coli in 7
      patients, Proteus in 4 patients, and in 3 cases abacterial leucocyturia; in 2
      patients with only one functional kidney, renal insufficiency was observed. In
      all cases, the diagnosis was confirmed by ultrasonography. The main etiological
      factors were urinary lithiasis in 10 patients (71%), followed by uropathy of the
      pyeloureteral junction in 4 patients (29%). Treatment consisted of primary
      nephrectomy in 10 cases; in 3 cases, primary nephrostomy was performed with a
      positive outcome and recovery of renal function in 2 subjects; in one case of
      renal failure treated by nephrostomy followed by conservative surgery, the
      patient did not survive. In conclusion, nephrectomy is advocated as the treatment
      of choice in the case of a damaged kidney and a normal contralateral kidney.
      Conservative treatment should be envisaged particularly in the case of a single
      kidney, or if the patient's state of health is poor. The best treatment consists
      of the detection and cure of the lithiasis which is the main etiological factor
      in this pathology.

PMID- 10953792
TI  - [Primary vesicoureteral reflux: report of 100 pediatric observations].
AB  - In this study, the authors have reported 100 cases of primary vesico-ureteral
      reflux (VUR) which occurred over a 7-year period. Patient age at presentation
      ranged from 1 month to 13 years, with a mean age of 3 years and 5 months.
      Overall, a higher rate of reflux was observed in the female population (63%)
      which was particularly evident after the age of 3 years, but with a male
      predominance during the first 12 months of life. In the majority of cases, the
      diagnosis of VUR was made following diagnosis and investigation of urinary
      infection (UI). A high level of UI was the most frequent sign of VUR (87% of
      cases), while in 6% of cases this disorder was diagnosed during the investigation
      of an uropathy which was found to be complex in all subjects. An analysis of 143
      ureteral reflux units (URU) showed that VUR was pathological only in 17% of
      cases, and that the reflux grade was I, II, III and IV in 47.4, 28.14, 11.11 and
      2.34% of cases respectively. DMSA scintigraphy in 38 patients showed signs of
      nephropathy in 24 cases, i.e., 14 scars and a decrease in kidney size in 9 cases,
      and an absence of fixation for one grade IV reflux. Forty subjects with 56 reflux
      units (34 grade I, II and 22 grade III, IV) were treated by antibiotic
      prophylaxis, with a positive outcome in 85% of cases in children under 2 years of
      age, compared to 40% for children aged over 2 years. Only 7 patients were treated
      by teflon endoscopic injection, and in one case a further injection was required;
      21 patients with 30 reflux units were treated by surgery at a mean age of 4
      years. In conclusion, VUR is a fairly common disorder, which is frequently
      detected via an IU; its potential gravity is associated with the risk of
      subsequent nephropathy.

PMID- 10953793
TI  - [Urinary candidiasis revealed by ureteral obstruction: report of 2 cases].
AB  - There has been an increase in the frequency of candidiasis urinary infections,
      which mainly affect diabetic or immunodepressed patients. However, the
      obstruction of the upper urinary tract by fungal infection is a rare occurrence.
      The introduction of novel antifungal agents has improved the treatment of fungal
      infection. In this study, two cases have been reported of urinary candidiasis
      infections with obstruction of the upper urinary tract which were successfully
      treated with fluconazole in combination with ureteral catheterization.

PMID- 10953794
TI  - [Retroperitoneal sarcoma: report of 6 cases].
AB  - Retroperitoneal soft tissue sarcomas (RPS) are uncommon tumors. The diagnosis is
      frequently made later in the evolution of the disease due to the absence of
      specific symptomatology. Surgery with total resection of the tumor is the
      treatment of choice, but is only possible in 38 to 75% of cases. Six cases of RPS
      have been retrospectively reviewed; the mean time to diagnosis was 5 months;
      diagnosis was established via CT scan, which determined the retroperitoneal tumor
      location and its relationship to the neighboring organs. The most common symptoms
      were the presence of an abdominal mass and accompanying abdominal pain; signs of
      urinary and vascular compression were not found until later. Surgery with total
      resection was performed in 4 cases, and with partial resection in 2 cases. The
      histological findings were as follows: 3 liposarcomas, 2 rhabdomyosarcomas, and 1
      fibrosarcoma. Tumor recurrence developed in 2 cases (liposarcomas), necessitating
      further surgery and complete resection. Two patients were lost to follow-up. RPS
      are characterized by locoregional relapse and metastases. Disease outcome depends
      on the histological type, tumor grade, and on the possibility of carrying out
      complete resection.

PMID- 10953795
TI  - [Bladder leiomyosarcoma: report of a case].
AB  - Leiomyosarcoma of the urinary bladder is an extremely rare disease. In this
      study, which also includes a review of the literature, a new case of urinary
      bladder leiomyosarcoma has been reported in a 65-year old male, which was
      detected during an investigation of total hematuria accompanied by burning upon
      micturition. The clinical examination was normal, but ultrasonography followed by
      bladder endoscopy showed the presence of a large bladder tumor. The definitive
      diagnosis of this type of tumor can only be made after histological and
      immunohistochemical investigation, and to avoid unnecessary surgery it is
      essential to first differentiate it from an inflammatory pseudosarcoma. Although
      in the present study the outcome following total cystoprostatectomy was favorable
      at 3 months follow-up, in general the prognosis is uncertain due to the
      potentially invasive character of this type of tumor. Given the limited number of
      studies on the subject treatment still remains controversial, but is essentially
      based on surgical excision, possibly with adjuvant chemotherapy.

PMID- 10953796
TI  - [Treatment of inflammatory urethral stenosis with endoscopic urethrotomy].
AB  - Urethral stricture, mainly consisting of cases of inflammatory stricture, is a
      frequent occurrence in Morocco. Numerous techniques have been proposed to treat
      these disorders, including internal endoscopic urethrotomy (IEU). Initially
      described by Otis and Maisonneuve using a blind approach, IEU was then further
      developed by Saches who carried out direct vision urethrotomy. It rapidly became
      established as the method of choice for primary treatment of urethral stricture,
      and classical surgery was limited to those cases in which this method had failed.
      However, although this technique is relatively simple and appears to be
      efficient, there is in fact a high relapse rate, necessitating repeated IEU;
      therefore at present there is a tendency to return to the classical methods of
      anastomotic resection and urethroplasty after the second or third IEU. Although
      the relapse rate is low for short, single or bulbar strictures, it is high for
      penile strictures and for those with accompanying severe periurethral fibrosis.
      In this study, we have reported the results of a homogeneous series of 149 cases
      of urethral stricture treated by internal urethrotomy. The aim of this
      retrospective study was to better define the indications for adopting this
      technique, and also to determine the reasons for failure. The various
      alternatives to IEU (resection, plasty) have been examined, as has their
      respective failure rate.

PMID- 10953797
TI  - [Fibrous pseudotumor of the vaginalis testis: report of a case].
AB  - In this study, the authors have reported a case of a benign fibrous pseudotumor
      of the tunica vaginalis testis in a 24-year old man who was admitted with a left
      scrotal mass. Scrotal ultrasound and surgical investigation demonstrated the
      presence of a left testicular tumor; radical orchiectomy was performed by
      inguinal route. Microscopic examination revealed a pseudotumor of the testicular
      tunica vaginalis. As this is an uncommon lesion and preoperative diagnosis is
      difficult, unnecessary radical orchidectomy is often carried out.

PMID- 10953798
TI  - [Isolated testicular tuberculosis: report of a case].
AB  - In this study, a case has been reported involving a 66-year old male who was
      admitted for scrotal pain on the right side with possible testicular involvement,
      but with no associated urinary disorder. At physical examination, the right
      testicle was found to have increased in volume: this was further confirmed by
      ultrasonography, but the findings were insufficient to exclude the hypothesis of
      testicular cancer. An exploratory orchidectomy by upper inguinal route was
      therefore carried out, and histopathological examination showed the destruction
      of testicular tissue by several granulomas, and caseous necrosis with giant
      cells. Antibacterial chemotherapy was administered after an i.v. urography found
      no evidence of abnormality or urinary disorder, thereby eliminating an active
      site of genitourinary tuberculosis. This case shows the importance of considering
      testicular tuberculosis in the differential diagnosis of testicular enlargement
      in a region where this disease is endemic, despite the absence of systemic
      pulmonary and urinary signs of tuberculosis.

PMID- 10953799
TI  - [Primary paratesticular malignant tumors: report of 6 cases].
AB  - The authors have made a study of 6 cases of malignant primary paratesticular
      tumor, and have also included a review of the literature on this topic. They
      emphasize the importance of the effect of histopathological type of tumor on
      disease outcome. There is an improved survival potential in cases where the
      tumors are differentiated, and discovered at an early date.

PMID- 10953800
TI  - [Testicular metastasis of prostatic adenocarcinoma: report of 2 cases].
AB  - Prostatic carcinoma metastasizing to the testis is an extremely rare occurrence.
      In this study, two new cases have been reported of unilateral testicular
      metastases from an adenocarcinoma of the prostate. Unlike primary tumors of the
      testis, this type of tumor develops later in life (between 50 and 60 years of
      age), and is in most instances unilateral. It is generally discovered
      accidentally during orchiectomy or autopsy. It is not always easy to establish a
      morphological diagnosis, as the macroscopic appearance of the tumor may be
      normal. However, microscopic investigation reveals the presence of neoplasms of
      the testis.

PMID- 10953801
TI  - [Penile emergencies].
AB  - The three main penile emergency situations have been examined so as to better
      define the clinical and therapeutic aspects. In the present study, a fracture of
      the penis (n = 12) occurred following a coital accident in 8 cases. In general, a
      clinical diagnosis was made and emergency surgical treatment appeared to be the
      most efficient means of preventing possible erectile malfunction. Mutilation of
      the penis was observed (n = 12) following traditional circumcision or
      circumcision performed by paramedical staff; or was due to self-inflicted
      mutilation and pyschiatric disorder (n = 6), and in one case to sexual deviation
      (n = 1) This category of accidents could be more adequately managed by the
      psychiatric treatment of certain patients and by better training of the personnel
      carrying out the circumcision. Priapism (n = 42) was due to sickle cell disease
      in 50% of cases, and relapse was noted in 10% of patients.

PMID- 10953802
TI  - Active life expectancy estimates for the U.S. elderly population: a
      multidimensional continuous-mixture model of functional change applied to
      completed cohorts, 1982-1996.
AB  - An increment-decrement stochastic-process life table model that continuously
      mixes measures of functional change is developed to represent age transitions
      among highly refined disability states interacting simultaneously with mortality.
      The model is applied to data from the National Long Term Care Surveys of elderly
      persons in the years 1982 to 1996 to produce active life expectancy estimates
      based on completed-cohort life tables. At ages 65 and 85, comparisons with extant
      period estimates for 1990 show that our active life expectancy estimates are
      larger for both males and females than are extant period estimates based on
      coarse disability states.

PMID- 10953803
TI  - The racial crossover in comorbidity, disability, and mortality.
AB  - This study analyzed one respondent per household who was age 70 or more at the
      time of the household's inclusion in Wave 1 (1993-1994) and whose survival status
      was determinable at Wave 2 (1995-1996) of the Survey on Asset and Health Dynamics
      Among the Oldest Old (AHEAD Survey). At age 76 at Wave 1, there was a racial
      crossover in the cumulative number of six potentially fatal diagnoses (chronic
      lung disease, cancer, heart disease, hypertension, diabetes, and stroke) from a
      higher cumulative average number for blacks to a higher average number for
      whites. Also, there was a racial crossover at age 86 in the cumulative average
      number of disabilities in the Advanced Activities of Daily Living (AADLs), from a
      higher average for blacks to a higher average for whites. Between Waves 1 and 2,
      there was a racial crossover in the odds of mortality from higher odds for blacks
      to higher odds for whites; this occurred at about age 81. The results are
      consistent with the interpretation that the racial crossover in comorbidity (but
      not the crossover in AADL disability) propelled the racial crossover in
      mortality.

PMID- 10953804
TI  - Racial differences in birth health risk: a quantitative genetic approach.
AB  - In the United States the gap between black and white babies' birth weights has
      remained largely unexplained. Rather than trying to measure all relevant
      variables, we used a genetically informative design to study the relative
      importance of genetic and environmental factors. Employing multiple indicators of
      "birth health risk," we found that the racial differences increased with the
      magnitude of the shared environmental effects. This suggested that possible
      genetic effects would not pertain to fetal genes, although genes affecting the
      mother's physical or physiological characteristics could be important because
      they contribute to shared environment in our analysis.

PMID- 10953805
TI  - Husbands' versus wives' fertility goals and use of contraception: the influence
      of gender context in five Asian countries.
AB  - Using data from Pakistan, India, Malaysia, Thailand, and the Philippines, we
      explore how gender context influences (1) husband-wife concordance in the demand
      for children and (2) the impact of each spouse's fertility preferences on
      contraceptive use. We also explore whether the husband's pronatalism can explain
      the wife's unmet need for contraception. The results suggest that gender context
      has little net effect on couples' concordance, but influences the relative weight
      of husbands' and wives' preferences in determining contraceptive use. Analysis of
      women's unmet need for contraception suggests that the husbands' pronatalism
      contributes to wives' unmet need, but only to a relatively small degree,
      especially in settings where unmet need is high. This is the case because the
      proportion of couples with differing fertility goals is small in most
      communities.

PMID- 10953806
TI  - Does female circumcision affect infertility and fertility? A study of the central
      African Republic, Cote d'Ivoire, and Tanzania.
AB  - This study explores the association between female circumcision and infertility
      and fertility, using information from the Demographic and Health Surveys (DHS).
      In Cote d'Ivoire and Tanzania, circumcised women had lower childlessness, lower
      infertility by age, and higher total fertility rates than women who were not
      circumcised; the reverse pattern prevailed in the Central African Republic. In
      all three countries, however, circumcised women grouped by age at circumcision
      did not have significantly different odds of infertility nor of having a child
      than did uncircumcised women, when the effects of covariates were controlled.
      Thus we find evidence suggesting that the practice of female circumcision does
      not have a statistically discernible effect on women's ability to reproduce.

PMID- 10953807
TI  - From austerity to prosperity? Migration and child poverty among mainland and
      island Puerto Ricans.
AB  - Analyses of migrants' economic circumstances typically use the native-born in the
      destination as a comparison group. We use the 1990 Census Public Use Microdata
      Samples for the United States and Puerto Rico to demonstrate the benefits of a
      comparative approach that includes data from both the origin and the destination.
      Specifically, the primary objective is to determine how and why the risk of child
      poverty is associated with migration from Puerto Rico to the United States. The
      results show that migration reduces the risk of child poverty, partly because
      better jobs are available on the mainland. Employment, human capital, family
      structure, and public assistance cannot completely explain observed differences.
      The results also show that the economic benefits of migration continue for the
      native-born on the mainland and that return migration to Puerto Rico is
      associated with impoverishment.

PMID- 10953808
TI  - You can go home again: evidence from longitudinal data.
AB  - In this paper we analyze the economic and demographic factors that influence
      return migration, focusing on generation 1.5 immigrants. Using longitudinal data
      from the 1979 youth cohort of the National Longitudinal Surveys (NLSY79), we
      track residential histories of young immigrants to the United States and analyze
      the covariates associated with return migration to their home country. Overall,
      return migration appears to respond to economic incentives, as well as to
      cultural and linguistic ties to the United States and the home country. We find
      no role for welfare magnets in the decision to return, but we learn that welfare
      participation leads to lower probability of return migration. Finally, we see no
      evidence of a skill bias in return migration, where skill is measured by
      performance on the Armed Forces Qualifying Test.

PMID- 10953809
TI  - The changing structure of school segregation: measurement and evidence of
      multiracial metropolitan-area school segregation, 1989-1995.
AB  - In this paper we examine aggregate patterns and trends in segregation among white
      (non-Hispanic), black, Hispanic, and Asian public school students in 217
      metropolitan areas during the period 1989-1995. We first describe a set of
      methodological tools that enable us both to measure the mutual segregation among
      multiple racial groups and to partition total metropolitan-area school
      segregation into geographic and racial components. Then we use these tools to
      examine patterns and trends in metropolitan-area school segregation. We find that
      the average levels of multiracial school segregation have been unchanged from
      1989 to 1995, but that this stability masks important shifts in the geographic
      and racial components making up average levels of total metropolitan school
      segregation. In particular, segregation between non-Hispanic white students and
      all other students has increased, on average, while segregation among black,
      Hispanic, and Asian student groups has declined. In addition, the contribution to
      average levels of total metropolitan segregation due to between-district
      segregation has grown, whereas the relative contribution of within-district
      segregation has declined.

PMID- 10953810
TI  - Growth in family income inequality, 1970-1990: industrial restructuring and
      demographic change.
AB  - Industrial restructuring and changing population composition frequently have been
      treated as competing explanations of growing U.S. income inequality. Using the
      Gini coefficient, we employ a model of conditional change to explore the relative
      effects of each on changes of family income distribution between 1970 and 1990,
      across 784 metropolitan areas and public use microdata areas (PUMAs). Changes in
      both industrial structure and population characteristics are found to have
      significant and opposite effects on family income distribution, although there
      are sharp differences by decade in the dynamics that underlie increasing
      inequality. Our central conclusion is that it is too soon to eliminate
      deindustrialization as a significant cause of increased earnings inequality.

PMID- 10953811
TI  - The meaning and measurement of race in the U.S. census: glimpses into the future.
AB  - The 1996 Racial and Ethnic Targeted Test (RAETT) was a "mail-out mail-back"
      household survey with an experimental design of eight alternative questionnaire
      formats containing systematic variations in race, instructions, question order,
      and other aspects of the measurement. The eight different questionnaires were
      administered to random subsamples of six "targeted" populations: geographic areas
      with ethnic concentrations of whites, blacks, American Indians, Alaskan natives,
      Asian and Pacific Islanders, and Hispanics. The major conclusion is that allowing
      multiple responses to the "race" question in the 2000 census (and other
      variations in measurement that were considered in RAETT) had only a slight impact
      on the measured racial composition of the population. Another finding was a
      dramatic reduction in nonresponse to the combined race/Hispanic-origin question
      relative to all other questionnaire formats. We conclude that the concept of
      "origins" may be closer to the popular understanding of American diversity than
      is the antiquated concept of race.

PMID- 10953812
TI  - The accuracy of survey-reported marital status: evidence from survey records
      matched to Social Security records.
AB  - Researchers have concluded that divorced persons often fail to report accurate
      marital information in surveys. I revisit this issue using surveys matched
      exactly to Social Security data. Older divorced persons frequently misreport
      their marital status, but there is evidence that the misreporting is
      unintentional. I offer some suggestions on how surveys can be improved.

PMID- 10953813
TI  - Effect of elastic neck strap on right thumb force and force angle during clarinet
      performance.

PMID- 10953814
TI  - Ammonium perchlorate contamination of Colorado River drinking water is associated
      with abnormal thyroid function in newborns in Arizona.
AB  - The Colorado River below Lake Mead, which supplies drinking water for
      approximately 20,000,000 people, is contaminated by ammonium perchlorate. We
      identified populations who were exposed and unexposed to perchlorate-contaminated
      drinking water and compared median newborn thyroid-stimulating hormone (TSH)
      levels after adjusting for age in days at measurement and for race/ethnicity.
      Median newborn TSH levels in a city whose drinking water supply was 100%
      perchlorate-contaminated water from the Colorado River below Lake Mead were
      significantly higher than those in a city totally supplied with non-perchlorate
      contaminated drinking water, even after adjusting for factors known or suspected
      to elevate newborn TSH levels. This ecological study demonstrates a statistically
      significant association between perchlorate exposure and newborn TSH levels. It
      suggests that even low-level perchlorate contamination of drinking water may be
      associated with adverse health effects in neonates and highlights the need for
      both further study and control of human low-level perchlorate exposure.

PMID- 10953815
TI  - Video display terminal workstation improvement program: I. Baseline associations
      between musculoskeletal discomfort and ergonomic features of workstations.
AB  - Associations between selected sites of musculoskeletal discomfort and ergonomic
      characteristics of the video display terminal (VDT) workstation were assessed in
      analyses controlling for demographic, psychosocial stress, and VDT use factors in
      273 VDT users from a large administrative department. Significant associations
      with wrist/hand discomfort were seen for female gender; working 7+ hours at a
      VDT; low job satisfaction; poor keyboard position; use of new, adjustable
      furniture; and layout of the workstation. Significantly increased odds ratios for
      neck/shoulder discomfort were observed for 7+ hours at a VDT, less than complete
      job control, older age (40 to 49 years), and never/infrequent breaks. Lower back
      discomfort was related marginally to working 7+ hours at a VDT. These results
      demonstrate that some characteristics of VDT workstations, after accounting for
      psychosocial stress, can be correlated with musculoskeletal discomfort.

PMID- 10953816
TI  - Video display terminal workstation improvement program: II. Ergonomic
      intervention and reduction of musculoskeletal discomfort.
AB  - The effects of an ergonomic intervention on musculoskeletal discomfort in 118
      video display terminal (VDT) users were assessed 1 year after intervention. The
      intervention consisted of recommended changes to workstations, which were based
      on the evaluation of 15 ergonomic characteristics. Compliance with the
      intervention was at least 75% for most workstation characteristics. Reduction in
      discomfort was substantial and was highest for the wrist/hand (57%), lower back
      (43%), and neck/shoulder (41%) severity of discomfort outcomes. Neither
      compliance with intervention on individual workstation characteristics nor
      summary intervention scores were associated with reduction in discomfort. Our
      results demonstrate that although reduction of musculoskeletal discomfort may be
      observed in the context of an intervention study, it may be difficult to link
      these benefits to specific interventions.

PMID- 10953817
TI  - Cancer mortality among the highest exposed US atmospheric nuclear test
      participants.
AB  - Of the estimated 205,000 military personnel who participated in the US
      atmospheric nuclear weapons testing program from 1945 to 1962, less than 1% had
      ionizing radiation doses that met or exceeded the current federal occupational
      guideline for dose of 5 rem (roentgen equivalents in humans) in a 12-month
      period. The objective of this study was to determine whether veterans who
      received the highest gamma radiation doses (n = 1010) have experienced increased
      cancer mortality compared with a group of Navy veterans who received a minimal
      radiation dose as participants of HARDTACK I (n = 2870). Mortality from all
      causes of death (relative risk, 1.22; 95% confidence interval, 1.04 to 1.44) and
      from all lymphopoietic cancers (relative risk, 3.72; 95% confidence interval,
      1.28 to 10.83) was significantly elevated among the 5-rem cohort compared with
      the Navy controls. The lack of statistically significant excesses in deaths from
      many of the known radiogenic cancers suggests that the observed excess mortality
      may be the result of many factors, of which radiation exposure was only one.

PMID- 10953818
TI  - Hearing conservation for farmers: source apportionment of occupational and
      environmental factors contributing to hearing loss.
AB  - Those who work on farms continue to have a strikingly high prevalence of hearing
      loss, despite efforts to promote hearing conservation in agriculture. To develop
      improved hearing conservation programs, we performed a source apportionment
      analysis for hearing loss in a large, multiphasic health survey, the New York
      Farm Family Health and Hazard Survey. We used information from audiometric,
      otoscopic, and tympanometric examinations; detailed general health and farm
      exposure interviews; and a second interview that focused on additional potential
      determinants of hearing loss. Hearing loss on audiometry was significantly
      associated with increased age, male gender, education through high school or
      less, lifetime years of hunting with guns, lifetime years of use of a grain
      dryer, and a history of spraying crops during the previous year. Hearing
      conservation programs for farmers should thus be directed toward reduction in
      noise exposure, both from occupational and non-occupational sources. Additional
      study is needed to evaluate the association seen between crop spraying and
      hearing loss.

PMID- 10953819
TI  - Lung function and work-related exposure in pig farmers with respiratory symptoms.
AB  - The present study was conducted to evaluate characteristics of pig houses that
      are associated with the development of respiratory morbidity in 100 swine
      producers with work-related respiratory symptoms. A standardized questionnaire
      for farm characteristics was used, and lung function was assessed immediately
      before and after feeding the pigs. Exposure to dust and endotoxin was determined
      by personal sampling. Among these farmers, baseline lung function results were
      shown to be negatively associated with duration of employment, number of pigs on
      the farm, manual feeding, and ventilation. The decrease in forced vital capacity
      and forced expiratory volume in 1 second over the feeding period was negatively
      correlated with air velocity, whereas respirable dust concentrations were shown
      to be significant predictors of maximal midexpiratory flow (MMEF25/75) decline.
      In conclusion, among symptomatic pig farmers, those with higher numbers of pigs
      and longer duration of employment are at highest risk for developing functional
      impairment.

PMID- 10953820
TI  - Prevalence of antibody to hepatitis A virus in drinking water workers and
      wastewater workers in Texas from 1996 to 1997.
AB  - To determine if wastewater workers had a higher prevalence of antibody to
      hepatitis A virus (anti-HAV) than drinking water workers, a convenience sample of
      Texas wastewater and drinking water workers was evaluated for risk factors by
      questionnaire and tested for anti-HAV. A total of 359 wastewater and 89 drinking
      water workers participated. Anti-HAV positivity was 28.4% for wastewater and
      23.6% for drinking water workers. After adjustment for age, educational
      attainment, and Hispanic ethnicity, the odds ratio for the association between
      anti-HAV positivity and wastewater industry employment was 2.0 (95% confidence
      interval, 1.0 to 3.8). Among wastewater workers, never eating in a lunchroom, >
      or = 8 years in the wastewater industry, never wearing face protection, and skin
      contact with sewage at least once per day were all significantly associated with
      anti-HAV positivity in a model that adjusted for age and educational attainment.
      Wastewater workers in this study had a higher prevalence of anti-HAV than
      drinking water workers, which suggested that wastewater workers may have been at
      increased risk of occupationally acquired hepatitis A. Work practices that expose
      workers to wastewater may increase their risk.

PMID- 10953821
TI  - Impact of a design modification in modern firefighting uniforms on burn
      prevention outcomes in New York City firefighters.
AB  - Our aim was to determine the impact of three different firefighting uniforms
      (traditional, modern, and modified modern) on the incidence and severity of
      thermal burn injuries, the major occupational injury affecting firefighters.
      Injury data were collected prospectively for the entire New York City Fire
      Department (FDNY) firefighting force wearing FDNY's traditional uniform
      (protective over-coat) from May 1, 1993 to August 31, 1993; FDNY's modern uniform
      (protective over-coat and over-pant) from May 1, 1995 to August 31, 1995; and
      FDNY's modified modern uniform (short sleeved shirt and short pants, rather than
      long-sleeved shirt and long pants, worn under firefighter's protective over
      clothes) from May 1, 1998 to August 31, 1998. Outcome measures were burn
      incidence and severity. Adverse outcomes were heat exhaustion and cardiac events.
      During this 12-month study, 29,094 structural fires occurred. The incidence rate
      for upper extremity burns was 2341 per 100,000 fires and for lower extremity
      burns, 2076 per 100,000 fires. With the change from the traditional to modern
      uniform, the distribution of burns per fire decreased significantly (P = 0.001)
      for upper extremity burns (86%) and lower extremity burns (93%). With the change
      from traditional to modern uniform, days lost to medical leave for upper or lower
      extremity burns decreased by 89%. The majority of burns occurred at the lower arm
      and mid-leg, and the change to the modern uniform decreased such burns by 87% and
      92%. Burn incidence and severity were not significantly affected by the change to
      the modified modern uniform. The distribution of heat exhaustion or cardiac
      events per fire was not significantly affected by the change from the traditional
      to modern uniform, and heat exhaustion was decreased (P < 0.001) by the change to
      the modified modern uniform. In conclusion, the modern uniform dramatically
      reduced burn incidence and severity without adverse impact. The modified modern
      uniform significantly reduced heat exhaustion without significantly affecting
      thermal protection.

PMID- 10953822
TI  - Work-related knee disorders in floor layers and carpenters.
AB  - Previous studies indicate an increased prevalence of knee disorders in some
      occupations possibly related to kneeling working positions. The purpose of the
      present study was to examine the relationship among knee-straining work, self
      reported knee-complaints, and physical signs of knee disorders. The duration of
      knee-straining work was estimated from videotapes of representative work tasks.
      Floor layers (n = 133), carpenters (n = 506), and compositors (n = 327) aged 26
      to 72 years without previous acute knee traumas were examined in a cross
      sectional study by questionnaire. A stratified random sample of the questionnaire
      responders; 67 floor layers, 127 carpenters, and 101 compositors had independent
      double examinations for physical signs of knee disorders. The videotapes showed
      that knee-straining work constituted 56% of working time for floor layers, 26%
      for carpenters, and none for compositors. The prevalences of self-reported knee
      complaints were positively associated with the amount of knee-straining work and
      were significantly different for the three trades. Floor layers and carpenters
      who were presently working in their trade had a higher prevalence of knee
      complaints than floor layers and carpenters who had left their trade. Age,
      seniority, weight, body mass index, smoking, and knee-straining sports activity
      had no significant effects. The clinical study showed a positive association for
      knee-straining work, hyperkeratosis, and bursitis. A similar pattern was found
      for signs of intraarticular knee disorders by one physician but not by another.
      The reproducibility of these signs was low. More studies are needed to define
      clinically important knee disorders for epidemiological studies.

PMID- 10953823
TI  - Hematological changes in hospital workers due to chronic exposure to low levels
      of ethylene oxide.
AB  - We conducted a cross-sectional study to determine whether occupational exposure
      to low levels of ethylene oxide can cause hematological abnormalities. Blood
      samples were collected from a group of 47 hospital workers who were exposed to
      ethylene oxide during a mean period of 6.6 years (standard error, 1.1). Ethylene
      oxide range levels measured were < 0.01 to 0.06 ppm. The control group,
      individually matched by age, sex, and smoking habits, consisted of 88 workers
      from the administrative sector. We found significant differences between the
      exposed and the control group in the frequency of workers with white blood cells
      lower than the normal range. Although there was no significant difference in the
      absolute mean number of the total white blood cells, we found an elevation in the
      absolute mean number of monocytes and eosinophils (P < 0.01) and a decrease (P <
      0.01) in the absolute mean number of lymphocytes in the exposed group compared
      with the control group. We also found an elevation (P < 0.01) in the percentage
      of hematocrit and the mean absolute number of the red blood cells, and a decrease
      (P < 0.01) in the mean absolute number of platelets, in the exposed group
      compared with the control group. The mean absolute number of eosinophils, red
      blood cells, and percentage of hematocrit was significantly higher, and the mean
      absolute number of lymphocytes and platelets was significantly lower, in the
      subgroups with a higher cumulative dose of exposure. A positive dose-response was
      found between cumulative dose exposure and the absolute mean number of
      eosinophils. In view of our findings, we suggest that the use of complete blood
      cells with differential in routine medical surveillance and for early detection
      of hygiene problems should be reexamined with special attention to the
      eosinophils count.

PMID- 10953824
TI  - Processing coordinate structures.
AB  - Coordination often involves syntactically like categories. Based on the results
      of four reading time studies, it is argued here that the syntactic like-category
      restriction is not grammatical. Coordination of unlike categories can be just as
      acceptable as coordination of like categories. However, syntactically like
      category coordination is processed faster than coordination of unlike categories
      even when the two sentence types are judged to be fully acceptable. Further,
      parallelism of conjuncts facilitates processing regardless of whether it is
      parallelism in the category of the conjuncts (a property which the grammar might
      regulate) or parallelism in the internal structure of the conjuncts (a property
      which the grammar does not regulate, on anyone's view). Parallelism did not
      facilitate processing when the structure of a subject and object were
      manipulated, implying that parallelism effects are largely limited to the
      conjuncts of a coordinate structure and not due simply to the repetition of a
      phrase with a particular shape.

PMID- 10953825
TI  - Are metaphors elliptical similes?
AB  - What is the relation between metaphors and similes? Aristotle's "comparison
      theory" holds that metaphors are elliptical similes: "Sam is a pig" is simply a
      short form of "Sam is like a pig." In contrast, it has been suggested that
      metaphors cannot be elliptical similes because metaphors are "stronger" than
      similes. We know metaphors are stronger, it is argued, because of examples
      involving corrections, such as "Peter is not just like a rock, he is a rock." The
      argument from corrections can be challenged on logical and empirical grounds. The
      ability to correct a simile with a metaphor does not entail that metaphors are
      stronger than similes when used on their own, which is likely to be the most
      frequent case. Although four experiments indicate that when corrections are
      involved, metaphors are indeed stronger than similes in several respects, alas a
      further four experiments indicate that these differences are largely eliminated
      when metaphors and similes are used on their own. We note that this pattern of
      results is consistent with the comparison theory, and we offer an explanation of
      the effects of corrections.

PMID- 10953827
TI  - "Typical Clinton: brazen it out".
AB  - Ten excerpts of both President Clinton's Grand Jury Testimony of August 17, 1998
      and of each of two interviews with Hillary Rodham Clinton (Today Show, January
      27, 1998; Good Morning America, January 28, 1998) were analyzed. In all of them,
      the topic under discussion was the President's insistence on his innocence in the
      Lewinsky case. Comparisons between the President and First Lady revealed long and
      short within-speaker pauses, respectively. His replies to questions average more
      than twice the length of hers. Comparisons were also made with other speech
      genres, including modern presidential inaugural rhetoric. In particular,
      President Clinton's statement of his innocence at the conclusion of an
      educational press conference on January 26, 1998 and his prepared statement at
      the beginning of his Grand Jury Testimony were found to vary notably from all the
      other corpora. Both are characterized by several of Ekman's (1985, p. 286)
      behavioral cues for the detection of deception.

PMID- 10953826
TI  - Semantic capacities of the right hemisphere as seen in two cases of pure word
      blindness.
AB  - Two patients with pure alexia were studied with tachistoscopically presented
      stimuli to examine factors influencing their ability to distinguish words from
      nonwords and to derive semantic information at exposures too brief for explicit
      letter identification. Both patients had profound right hemianopia and
      computerized tomography (CT) evidence of splenial destruction. Both patients were
      successful in making word/nonword decisions for high-frequency, but not low
      frequency, words. They could judge semantic class membership reliably for such
      common categories as animals and vegetables, but not for arbitrarily selected
      categories, such as office-related items. Judgments about the gender of people's
      names and place versus person name distinctions were made with high reliability.
      Results are interpreted as evidence for limited word recognition and semantic
      processing capacity in the right hemisphere.

PMID- 10953828
TI  - Case-mixing effects on spelling recognition: the importance of test format.
AB  - In a multiple-choice spelling recognition test, 56 university students were more
      accurate on more regular than irregular words, and on lower-case than mixed-case
      words, with the case mixing effect greater for irregular than regular words. In
      Experiment 2, the same words were presented singly in correct or incorrect
      spellings and distortion of word shape was achieved by case mixing (32 subjects)
      or by alternating the size of lower-case letters within a word (32 subjects). The
      main effects of regularity and distortion were replicated and the effect of
      distortion was greater for incorrect than correct stimuli, with correctly spelled
      words suffering a decrement in accuracy of less than 5 percentage points. Case
      mixing had a greater effect than size mixing on response latencies. In Experiment
      3, with comparable test procedures, case mixing interacted with regularity in the
      subjects analysis for the multiple choice format, but not the single presentation
      format. This result indicates that comparisons based on visual configuration may
      be an artifact of multiple-choice tests.

PMID- 10953829
TI  - [Cost-effectiveness analysis of 2 strategies of Helicobacter pylori eradication:
      results of a prospective and randomized study in primary care].
AB  - BACKGROUND: To analyze cost-effectiveness of two different strategies to treat H.
      pylori infection in peptic ulcer in the primary care setting. PATIENTS AND
      METHODS: Consecutive patients with endoscopic diagnosis of peptic ulcer were
      randomized to one of two strategies: a) treatment during 7 days with omeprazole,
      tetracycline, metronidazole and bismuth subcitrate ("quadruple" therapy) and if
      failure second-line treatment with omeprazole, amoxycillin and clarithromycin
      during 7 days (OCA7), and b) initial treatment with OCA7 and if failure treatment
      with "quadruple therapy". End point was eradication 8 weeks after last treatment
      dose. Direct and indirect costs were estimated (euros, 1997) and a cost
      effectiveness analysis using a decision-tree model was undertaken after real
      clinical data. 95% confidence intervals are given. RESULTS: After screening 255
      patients, 97 were finally included. 48 patients were given strategy a and 49
      strategy b. Eradication was obtained (intention-to-treat) in 72.9% (CI 95%: 58.2
      84.7) in group a versus 91.8% (CI 95%: 80.4-97.7) (p < 0.05) in group b. Mean
      cost per case treated was lower in group a (237 versus 268 euros) but cost per
      case eradicated was lower in group b (320 versus 296 euros). The cost was
      primarily determined by efficacy. CONCLUSIONS: Treatment with OCA7 followed by
      rescue with "quadruple" therapy if failure is more efficient in our area that the
      inverse strategy. Efficiency is mostly determined by efficacy.

PMID- 10953830
TI  - [Food intake, dietary habits and nutritional status of the population of Reus
      (X): Evolution of the diet and the contribution of macronutrients to energy
      intake (1983-1999) by age and sex].
AB  - BACKGROUND: To study the evolution of the diet and the nutritional intake between
      1983 and 1999, by age and sex. SUBJECTS AND METHODS: We performed a series of
      analysis of the food intake on a representative sample of the population of Reus
      (aged 10-69 years). Dietary intake was estimated using the 24-hours recall
      method. In 1999 the sample size was 839 individuals, 41% of them having taken
      part in the studies since 1983. Results are shown as mean (standard deviation).
      RESULTS: In 1999, the energy intake was 2524 (582) kcal in men aged 35-44 years
      (n = 57), and 1827 (490) kcal in women (n = 95) (p < 0.001 between sexes). The
      energy intake decreases with age (significant trend [p < 0.001] between 15-69
      years) and it is higher in men than in women in all the age groups studied. When
      comparing similar age groups, we observe that this energy intake has not changed
      significantly since 1983. Between 1983 and 1999 the contribution of the
      macronutrients to the total energy intake has become more similar between ages
      and sexes. In 1999, in men aged 35-44 years a 15.6% of the energy came from
      proteins, 42% from fat and 42.5% from carbohydrates; in women of the same age: a
      17.3% of the energy came from proteins, 42.4% from fat and 40.3% from
      carbohydrates). During this period we observed, however, remarkable changes in
      the diet which imply the increasing participation of the dairy products,
      vegetables and meat in the energy intake, or the significant decrease of the role
      of tubers, eggs and visible fat. CONCLUSIONS: Our population maintains an energy
      intake without significant changes, and it presents a trend towards a progressive
      uniformity of the nutritional balance between the different ages and sexes,
      although there are significant changes in some components of the diet.

PMID- 10953831
TI  - [Prospective study of patients who leave the emergency department before being
      seen by the physician].
AB  - BACKGROUND: To define epidemiological characteristics, the main reasons, and
      outcome of patients who leave the emergency department (ED) without being seen by
      a physician. PATIENTS AND METHODS: We performed a prospective survey of patients
      who left the ED before medical visit over a period of 26 consecutive weeks. For
      every non-visited patient (NV), the next visited patient (V) was included as a
      control. Clinical and epidemiological data, reasons to leave ED and outcome were
      obtained from clinical records and personal telephone interview. RESULTS: Out of
      a total of 21,022 patients who were attended in the ED, 383 (1.8%) were NV. To be
      under 50-year-old, to come the ED alone, to be previously visited by a community
      physician, and to previous expect short waiting times for ED visit were
      associated with higher risk for being NV (p < 0.01, p < 0.01, p < 0.05 and p <
      0.0001, respectively). The main reasons noted to leave the ED were: feeling
      better (35%), feeling too sick to wait longer (30%) and being too angry to wait
      (25%). Only 46% of the NV looked for medical care in the 72 following hours and
      6.5% of them needing to be further to hospital. NV-patients considered as
      suffering a serious pathology at ED arrival, and those being visited by a
      community physician previously to go to ED were found to be at increased risk to
      be subsequently admitted (p = 0.01 and p = 0.001, respectively). CONCLUSIONS:
      Patients who leave ED department before being seen by a doctor are usually young,
      literate, have not previously visited their community physician, and consulted
      for minor complaints. The main reason to leave is their own impression of
      suffering a minor disease, and less than 50% visit another physician after their
      leaving, being the rate of hospital admission low. We should be particularly
      cautious with those patients referred by a community doctor and those identified
      as to have a seriously affected health status at their arrival at the hospital,
      since they are at increased risk to be admitted.

PMID- 10953832
TI  - [Relationship between iron stores and diabetes mellitus in patients infected by
      hepatitis C virus: a case-control study].
AB  - BACKGROUND: To investigate whether the high prevalence of diabetes observed in
      patients infected by the hepatitis C virus (HCV) is associated to iron stores.
      PATIENTS AND METHODS: Serum ferritin levels were determined in 123 patients
      infected by HCV (55 diabetic and 68 non-diabetic). RESULTS: Serum ferritin
      concentrations were higher in diabetic than in non-diabetic patients (205 ng/ml
      [14-861] vs. 58 ng/ml [15-494]; p < 0.0001). CONCLUSIONS: Serum ferritin levels
      are related with the presence of diabetes in patients infected by HCV.

PMID- 10953833
TI  - [Helicobacter pylori eradication in gastroduodenal ulcer: good, fine and not
      expensive].

PMID- 10953834
TI  - [C virus, iron and sugar].

PMID- 10953835
TI  - [Cardiomyopathy in diabetes mellitus].

PMID- 10953836
TI  - [A comparative study of HLA-DR phenotype in children with celiac disease from
      Aragon and in control population from the same region].

PMID- 10953837
TI  - [Spontaneous bacterial peritonitis caused by Alcaligenes xylosoxidans].

PMID- 10953838
TI  - [Pancytopenia probably induced by metamizol].

PMID- 10953839
TI  - [Fatal cerebral malaria caused by Plasmodium falciparum after treatment with
      exchange transfusion].

PMID- 10953840
TI  - [Expression of Epstein-Barr virus genome in lymphomas of HIV-infected patients].

PMID- 10953841
TI  - Packing and stents in endonasal surgery.
AB  - Nasal packing is used primarily to control bleeding in epistaxis and after
      surgical procedures to the nose such as septoplasty, turbinate and paranasal
      sinus surgery. It is also used for internal stabilisation after operations
      involving the cartilaginous-bony skeleton of the nose. Apart from haemostasis,
      packing is used to prevent synechiae or restenosis, particularly after surgery.
      Generally accepted standards regarding the materials which should be used for
      packing, how long the packing should be left in place or the indications for
      nasal packing are lacking (Egelund and Jeppessen, 1992; Hosemann, 1996; Weber et
      al., 1996b). For example, many authors do not use packing at all provided that
      there is no heavy bleeding during or after the operation. Of those who use
      packing, some remove it on the day of the operation, others up to 5 days
      postoperatively (for overview see Weber et al., 1996b). Most publications
      describe experience with packing materials developed or preferred by the authors.
      Results of comparative studies on the nature and duration of packing are listed
      in Table 1. The currently available materials are reviewed and their respective
      properties, indications and risks are outlined.

PMID- 10953842
TI  - A prospective treatment trial of nasal polyps in adults with cystic fibrosis.
AB  - This is the first prospective, randomised, double-blind trial of the treatment of
      nasal polyps in cystic fibrosis. We found that betamethasone nasal drops showed a
      statistically significant reduction in polyp size in comparison to placebo.

PMID- 10953843
TI  - Nasal pH and saccharin clearance are unrelated in the physiologically normal
      nose.
AB  - A group of 56 asymptomatic non-smoking men was prospectively recruited to study
      the relationship between nasal mucosal pH and saccharin clearance rate. No
      significant relationship was found between the two variables (Pearson correlation
      coefficient = -.105, p = 0.44). This finding suggests that in vivo mucociliary
      flow rates are resistant to change within the pH range of the physiologically
      normal nose.

PMID- 10953844
TI  - Bactrim reduces the inflammatory response in a murine model of acute
      rhinosinusitis.
AB  - OBJECTIVE: To determine whether treatment with an antibiotic (trimethoprim
      sulfamethoxazole) reduced the inflammatory response in a murine form of
      Streptococcus pneumoniae-induced rhinosinusitis. DESIGN: We randomized 18 C57BL/6
      mice to either treatment with intraperitoneal trimethoprim-sulfamethoxazole
      (Bactrim, 30 mg/kg) or no treatment (control). After 2 days, we inoculated all
      C57BL/6 mice intranasally with a Bactrim-susceptible strain of Streptococcus
      pneumoniae, ATCC 49619, suspended in Trypticase soy broth. At day 5 after
      bacterial inoculation, we sacrificed the mice and prepared histopathologic
      sections of their sinuses after culturing their nasal cavities by lavage.
      SETTING: Animal care facility at a tertiary, academic institution. METHODS: The
      histopathologic sections of the sinuses were examined in a blind manner for the
      percent of sinus cavity area occupied by neutrophil clusters, and for the number
      of neutrophils per square millimeter of sinus mucosa. RESULTS: The Bactrim group
      had a significantly smaller sinus area occupied by neutrophil clusters (1.58% +/-
      1.13 vs 4.38% +/- 3.41; P < 0.05), significantly fewer neutrophils infiltrating
      the mucosa (58.81 +/- 29.63/mm2 vs 105.85 +/- 48.49/mm2; P < 0.05), and
      significantly less growth of Streptococcus pneumoniae colonies in the intranasal
      cultures (8 few and 1 moderate vs 3 few, 3 moderate, and 1 many; P = 0.05)
      compared to the control group. CONCLUSION: In our murine model of acute
      rhinosinusitis, Bactrim decreased the number of neutrophil clusters in the sinus
      cavities, the number of neutrophils infiltrating the sinus mucosa, and the growth
      of Streptococcus pneumoniae. We propose that our murine model can be used for the
      study of the pathophysiology and treatment of acute rhinosinusitis.

PMID- 10953845
TI  - A review of practical guidelines for correction of the deviated, asymmetric nose.
AB  - Repair of the twisted nose presents a challenge, as often functional problems as
      well as aesthetic deformities must be addressed. Traditional correction of the
      deviated nose involves septal correction, separation of both upper lateral
      cartilages from the septum and bony pyramid manipulation after osteotomies.
      Nowadays autogenous cartilage grafts are being used for repositioning,
      reinforcement, recontouring and reconstruction of virtually every component of
      the nasal skeleton. These restructuring techniques follow the modern principles
      mentioned above and may well be applied to the deviated asymmetric nose. The
      grafting manoeuvres increase the stability of the realigned cartilaginous nasal
      framework, including the nasal septum, but may also be used for camouflaging
      purposes. The large number of possible individual anatomic variations including
      facial asymmetry does call for a systematic approach based on succinct
      individualised analysis.

PMID- 10953846
TI  - Impact of short-time nasal intubation on postoperative respiration.
AB  - Until now few data on postoperative nasal respiration after nasal intubation is
      known which is of special importance for surgery, where postoperative
      intermaxillary fixation is necessary. This study was planned to acquire
      information about nasal breathing during the first postoperative week. Twelve
      patients treated for mandibular retrognathism were examined repeatedly by way of
      anterior active rhinometry, acoustic rhinometry, and rhinoresistometry before and
      after surgery over one week. In addition the subjective evaluation was checked on
      a visual analogue scale. Following intubation, significant changes in "objective"
      and subjective measurements of nasal respiration could be noted only on the
      second postoperative day. Comparing rhinomanometric and subjective data, a
      correlation could be found on postoperative day two only. In this study group
      short-time nasal intubation had no significant impact on postoperative
      respiration.

PMID- 10953847
TI  - The technique of nasendoscopy in the evaluation of nasolacrimal duct obstruction
      in children.
AB  - Epiphora in infancy is most commonly the result of failure of canalisation of the
      nasolacrimal duct and most cases resolve spontaneously within 12 months. Lacrimal
      probing is the standard operative treatment when conservative expectant
      management fails. While this carries a high success rate, it does not reliably
      localise the site of obstruction, can create a false passage and may induce
      traumatic stenosis in the lacrimal passages. Nasendoscopy in conjunction with the
      lacrimal probing overcomes these problems as the procedure is performed under
      direct vision. The precise site of opening of the nasolacrimal duct is
      ascertained, the nature of obstruction established and the risks of false passage
      creation minimised. We report this technique of endoscopic assessment of lacrimal
      probing, and the outcome results of twenty such procedures performed on thirteen
      children.

PMID- 10953848
TI  - Acute candidiasis of the oro- and hypopharynx as the result of topical intranasal
      steroids administration.
AB  - Topical nasal steroids have become increasingly popular for the treatment of
      allergic and other types of rhinitis. However, undesirable local effects of
      intranasal steroids, such as nasal irritation and burning, crusting and epistaxis
      are quite common. Candidiasis of the pharyngeal mucosa is a complication, which
      has not been described so far after treatment of rhinitis with intranasal topical
      corticosteroids. Between March 1997 and September 1998, we managed to treat
      successfully three patients with acute erythematous candidiasis of the pharynx,
      which was the result of the use of intranasal topical steroids. Mechanism,
      clinical features of acute pharyngeal candidiasis, differential diagnosis and
      treatment are discussed.

PMID- 10953849
TI  - The disappeared disease: tuberculosis of the nasal septum.
AB  - Recent advances in chemotherapy have reduced the incidence of upper respiratory
      tract tuberculosis. Tuberculosis of the nose is mainly by secondary infection to
      pulmonary tuberculosis via contagious, hematogenous or lymphatic routes. Primary
      infection of the nose is rare but possible when self-cleansing mechanism and
      lysosomal activity, of the nose is lost. A 45-year-old Korean woman with the
      chief complaints of nasal obstruction, crusting, and recurrent episodes of
      epistaxis is presented. Physical examination of the nose revealed friable, easily
      bleeding masses with crusts on both sides of the septum. The appearance and
      consistency of the lesions were different from those of nasal polyps. Chest and
      sinu X-rays revealed no active lesions. Tuberculin skin test was positive and the
      biopsied specimen proved to be consistent with tuberculosis. Her condition
      improved after anti-tuberculous medication for about 6 months.

PMID- 10953850
TI  - Unilateral choanal atresia. A possible indication for computer aided surgery? "A
      report of two cases".
AB  - Choanal atresia (CA) is a congenital obstruction of the posterior nose. Bilateral
      CA is a paediatric emergency and must be treated surgically in the first few
      weeks after birth. This is in contrast to unilateral CA, because surgical
      management can be planned more selectively. Transpalatinal surgery for CA is a
      safe procedure. The endonasal technique is minimally invasive and less traumatic;
      however, a major disadvantage is a limited field of vision. Computer aided
      surgery using images acquired by computer tomography (CT) or magnetic resonance
      imaging (MRI) is an application that has emerged in the last few years. This
      application provides an additional safety factor for endoscopic surgery to
      resolve choanal atresia, especially in cases of another malformation. We report
      results from two cases of unilateral CA who were surgically managed with Computer
      aided surgery.

PMID- 10953851
TI  - Endocarditis prophylaxis revisited: experimental evidence of efficacy and new
      Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis.
AB  - Because of its severity, it is agreed that infectious endocarditis should be
      prevented whenever possible. Determining adequate prophylactic measures involves
      establishing (a) the patients at risk, (b) the procedures that might provoke
      bacteraemia, (c) the most effective prophylactic regimen, and (d) a balance
      between the risks of side effects from prophylaxis and of developing infectious
      endocarditis. Patients at risk and procedures inducing bacteraemia have been
      identified by clinical studies. On the other hand, the efficacy of prophylactic
      antibiotics has been based on animal studies. Randomised, placebo-controlled
      studies do not exist in humans because they would require large patient numbers
      and would raise ethical issues due to the severity of the disease. Case-control
      studies have indicated that infectious endocarditis prophylaxis is effective, but
      prevents only a limited number of cases. Animal experiments have revealed several
      key issues for human application. First, antibiotics do not prevent the early
      stages of valve colonisation, but rather kill the microorganisms after their
      attachment to the cardiac lesions. Second, the duration of antibiotic presence in
      the serum is critical. Under experimental conditions, the drugs must remain above
      their minimal inhibitory concentration for the organisms for > or = 10 h, to
      allow time for bacterial clearance from the valves. Third, antibiotic-induced
      killing is not the only mechanism allowing bacterial clearance. Other factors,
      such as platelet microbicidal proteins, may act in concert with the drugs to
      sterilise the lesions. Recommendations for prophylaxis have recently been revised
      in Europe and the USA. New information has improved the definition of groups at
      risk. Since most cases of infectious endocarditis are not preceded by medical
      procedures, primary prevention of infectious endocarditis should target infected
      foci responsible for spontaneous bacteraemia (e.g. poor dental hygiene). The
      purpose of this article is to update the existing recommendations in Switzerland,
      under the perspective of changing epidemiology, the availability of new drugs,
      and harmonisation with recommendations in other countries.

PMID- 10953852
TI  - Haematopoietic stem cell transplant activity in Switzerland 1997/1998: a report
      by the STABMT. Swisstransplant Working Group Blood and Marrow Transplantation.
AB  - Data on haematopoietic stem cell transplants done in Switzerland in 1997 and 1998
      are reported. A total number of 532 autologous and 150 allogeneic procedures were
      performed during this period. Detailed information on indications, use of
      transplant technology and short-term outcome is provided. These data reflect the
      current use of haematopoietic stem cell transplantation in Switzerland and may be
      used for patient counselling and health care planning.

PMID- 10953853
TI  - Applying some UK Prospective Diabetes Study results to Switzerland: the cost
      effectiveness of intensive glycaemic control with metformin versus conventional
      control in overweight patients with type-2 diabetes.
AB  - OBJECTIVE: The results of the metformin substudy of the United Kingdom
      Prospective Diabetes Study (UKPDS) were applied through modelling techniques to
      the Swiss setting, allowing a cost-effectiveness analysis of the management of
      overweight type-2 diabetes patients with either conventional glycaemic control or
      intensive control with metformin from the Swiss third-party payer perspective.
      METHODS: Occurrence of diabetes-related complications was simulated using a
      Markov model. Probabilities for complications were taken from the UKPDS, and
      costs were retrieved from published sources. Total direct costs (costs of
      diabetes therapy plus costs of treating complications) and survival over an 11
      year period were determined for cohorts randomised to either conventional
      glycaemic control or intensive control with metformin. Changes in life expectancy
      were calculated for conventional versus intensive control with metformin.
      Extensive sensitivity analysis was performed. RESULTS: Mean costs per patient
      over the 11-year follow-up period (discounted at 5% per annum) were CHF 10,877
      and CHF 9950 for patients randomised to either conventional control or intensive
      control with metformin respectively. Intensive control with metformin led to
      improved survival (0.43 life-years gained per patient) over the 11-year-period.
      Outcomes were most sensitive to variations in the acquisition costs of metformin.
      Changes in the event rates and costs related to myocardial infarction, renal
      failure, and stroke also had important impacts. CONCLUSIONS: Within the
      limitations of the modelling study, intensive glycaemic control with metformin
      was cost- and life-saving in overweight type-2 diabetes patients in the Swiss
      setting.

PMID- 10953854
TI  - [Advice to HIV infected persons travelling to tropical or subtropical
      destinations].
AB  - Many HIV-infected persons travel from temperate zones to (sub)tropical
      destinations. HIV-specific immigration issues, medical resources abroad and
      problems regarding travel with multiple medication need to be anticipated. When
      prescribing immunisations and specific chemoprophylaxis, the stage of
      immunodeficiency as well as drug interactions with antiretrovirals must be taken
      into account. Live vaccines may be contraindicated. With good pretravel advice
      the risk of severe health problems is low for most HIV-infected travellers.

PMID- 10953855
TI  - [Brain and skin].

PMID- 10953856
TI  - [Cell division genes and proteins in bacterial cells].
AB  - In this review, genes and proteins involved in cytokinesis and cell proliferation
      of cell-wall bacteria and mycoplasms are considered. We hope that this
      comparative analysis of genes and proteins of phylogenetically distant bacteria,
      including the minimal cells of mycoplasmas, can be useful for understanding the
      basic principles of prokaryotic cell division. The ftsZ gene was found among
      representatives of all bacterial groups. The recent data indicate that FtsZ
      protein plays the central role in the process of bacterial cell division. FtsZ
      protein was revealed in all Eubacterial groups (including mycoplasmas), in
      Archaebacteria and chloroplasts, All FtsZ proteins are able to form
      protofilaments as a result of polymerization in vitro and demonstrate GTF-ase
      activity. On the base of these properties and some similarities in amino acid
      sequences with tubulins, it has been suggested that FtsZ protein is an
      evolutionary ancestor of Eukaryotic tubulins. On the earliest stage of bacterial
      cytokinesis FtsZ protein assembles into a submembranous Z-ring which encircles
      bacterial cell in the predivisional site. Some other bacterial proteins take part
      in stabilization and contraction of the Z-ring, which is considered as a
      cytoskeleton-like bacterial structure.

PMID- 10953857
TI  - [Ultrastructure and mechanism of separation of macroconidia in Monilia fructigena
      Pers].
AB  - Monilia fructigena macroconidia are characterized by availability of endoplasmic
      reticulum cisternae which are arranged parallel to one another, and large
      globules of polyphosphates reserve in vacuoles. During the liberation of
      macroconidia the following processes occur: plugging of the septal pore by plug,
      development of second continuous septum, rupture of the outer electron dense
      layer of cell wall, and strict separation.

PMID- 10953858
TI  - [Intranuclear structures containing RNA maturation factors in early vitellogenic
      oocytes of Rana temporaria].
AB  - We have examined the distribution of RNA processing factors in the germinal
      vesicle (GV) of the common frog Rana temporaria during early vitellogenesis by
      immunostaining on light- and electronmicroscopic levels and by in situ nucleic
      acid hybridization. Small nuclear RNPs (snRNP) and factor SC35 involved in pre
      mRNA splicing occur in lampbrush chromosome loops and numerous granules 1-3
      microns in size. These granules are identical to B snurposomes of Xenopus laevis
      and Notophtalmus viridescens described earlier (Wu et al., 1991). Some of B
      snurposomes are attached to homologous loops of lampbrush chromosomes.
      Immunofluorescent study of Cajal bodies/coiled bodies (CB) showed that sometimes
      CB have B snurposomes attached to their surface. In this case splicing factor
      SC35 is found in B snurposomes and B-like inclusions in CB matrix. In CB without
      attached B snurposomes splicing factor SC35 localizes throughout the whole
      organelle. Staining of GV spreads with antibodies against nucleolar protein NO38
      revealed this protein in CB, nucleoli and micronucleoli. Using in situ nucleic
      acid hybridization and immunofluorescent staining we have found that on GV
      spreads from hibernating frogs B snurposomes contact nucleoli. Nucleoli contain
      snRNP. These data suggest that nucleoli may be storage sites of snRNPs during
      natural inactivation of RNA synthesis. During winter season in Rana temporaria GV
      nucleoli become compacted and a number of micronucleoli (less than 2 microns)
      dramatically increases. Analysis of micronucleoli showed that they contain rRNA,
      protein NO38, trace amount of U3 small nucleolar RNA and do not contain
      fibrillarin, involved as U3 in pre-rRNA processing. We suggest that decrease of
      rRNA synthesis during frog hibernation results in transformation of part of
      nucleoli in micronucleoli.

PMID- 10953859
TI  - [Metabolic heterogeneity of glycogen in hepatocytes of patients with liver
      cirrhosis].
AB  - Concentrations of the total glycogen (TG) and of its labile and stable fractions
      (LF and SF, respectively) were determined in hepatocytes of portal and central
      zones of the normal human liver and in the liver of patients with cirrhosis of
      viral and alcohol etiology. Using the PAS reaction, TG and its LF and SF were
      revealed in histological sections of the material obtained by liver punction
      biopsies. Concentrations of TG and its fractions were measured by television
      cytophotometry. In liver cirrhosis, concentrations of TG, LF, and SF in both
      zones of the hepatic lobule were much higher than in the normal liver. The ratio
      between hepatocyte TG concentration in the portal zone and that in the central
      zone (P/C ratio), both in norm and in viral cirrhosis, exceeds 1.0 to reach,
      respectively, 1.26 +/- 0.02 and 1.03 +/- 0.01. The glycogen fraction composition
      in cells of both liver lobule zones in viral cirrhosis does not significantly
      differ from that in norm. On the contrary, in the liver of patients with
      alcoholic cirrhosis, the P/C ratio falls to 0.82 +/- 0.02 to be accompanied by
      qualitative changes in glycogen composition.

PMID- 10953860
TI  - [Development of blunt Tilletia caries (D.C.) Tul. pathogen on embryogenic wheat
      callus].
AB  - The development of Tilletia caries on embryogenic and morphogenic wheat calluses
      from germination of spores up to sorus formation have been investigated.
      Pathogene growth was similar in variants with wheat calluses of susceptible
      species Triticum aestivum and resistant species T. timopheevii, but intensity of
      its development of embryogenic calluses of both species was lower, than on
      morphogenic. Necrosis of parenchyma-like cells was more distinct in the
      embryogenic than in morphogenic calluses. It was combined with low accumulation
      rate of infected cells in embryogenic calluses. Necrosis reduced the healthy cell
      reproduction in meristem-like cells of morphogenic calluses and thereby
      additionally decreased resistance of morphogenic calluses to pathogene.

PMID- 10953861
TI  - [Apoptosis of L929 cells induced by tumor necrosis factor].
AB  - We investigated the mode of TNF-dependent death of L929 murine fibroblasts and
      the influence of overexpression of bcl-2 family genes on this process. Based on
      morphological and biochemical data it has been shown that L929 cells died after
      TNF treatment by apoptosis irrespective of TNF dose and protein synthesis
      inhibition. Analysis of bcl-2 family gene transfectants revealed a down
      regulation of TNF-induced apoptosis by bcl-2 and bclX overexpression, and an up
      regulation by bax gene.

PMID- 10953862
TI  - [Energy metabolism in wheat roots during modification of cell surface].
AB  - A study was made of dynamics of wheat production, intensity of respiration and
      changes in bioelectric characteristics of exised roots. Response reactions of two
      wheat varieties were compared in the process of adaptive reactions. The varieties
      differed in bioelectric characteristics of root cells in intact seedlings grown
      in CaCl2 and EDTA containing media. Different changes of membrane characteristics
      of root cells were observed: in soft wheat MP and Rin increased, but in hard
      wheat these decreased after a 5 h incubation of excised root. The rate of heat
      production was at the same level in both wheat varieties, but oxygen absorption
      of the root cells was lower in hard wheat compared with soft wheat. The rate of
      respiration of excised roots was stable in EDTA-containing medium. The obtained
      data allow to discuss more in detail the role of Ca(2+)-ions in the regulation of
      cell functions under formation of adaptive processes as the tissue level.

PMID- 10953864
TI  - [Sensitivity of the hog slater Asellus aquaticus to the toxic effects of heavy
      metals during different periods of ontogenesis, during different seasons and at
      different temperatures].
AB  - A study was made of acute toxic effects of Cd+, Cu+, Al+, Pb+, Ni+, Mn+ and Zn+
      ions on embryos, juveniles, and adults of Asellus aquaticus L. at 19 and 29
      degrees C, when examined in different seasons of the same year. The highest
      sensitivity to heavy metals was displayed by embryos. The metal sensitivity
      commonly decreases with age, however, during hormonal rearrangements associated
      with reproduction this was seen to increase again. For all age groups the heavy
      metal toxicity increases with increased temperature rises. The importance of a
      more strict control of water quality in the system of lakes and rivers is
      suggested, especially in spring and summer time when the mass reproduction of
      hydrobionts occurs.

PMID- 10953863
TI  - [Effect of polyamine synthesis inhibitors separately and in combination with
      epidermal growth factor on fusion of lysosomes with phagosomes and F-actin level
      in mouse peritoneal macrophages].
AB  - Effects of polyamine (PA) synthesis inhibitors--alpha
      difluoromethylornithinchloride (DFMO) and alpha-methylornithinchloride (MO)-
      separately or in combination with the epidermal growth factor (EGF)--on lysosome
      phagosome fusion (P-LF) and F-actin content in murine peritoneal macrophages were
      studied using fluorescent dye Acridine orange for lysosome labelling, FITC
      phalloidin for F-actin, and yeast cells as a target. DFMO and MO significantly
      inhibited P-LF and decreased F-actin content in murine peritoneal macrophages. A
      combination of DFMO and MO with EGF failed to inhibit P-LF or to decrease F-actin
      content in these cells. The results obtained with DFMO and MO suggested new
      cellular targets of their effects. These results may be extended to cancer
      research to provide a rationale for clinical trials using combinations of EGF
      with DFMO or MO.

PMID- 10953865
TI  - A highly repeated FCP centromeric sequence from chaffinch (Fringilla coelebs:
      Aves) genome is revealed within interchromosomal connectives during mitosis.
AB  - A highly repeated FCP (Fringilla coelebs PstI element) sequence was localized by
      FISH in centromeric regions of all chromosomes of the chaffinch. Besides, FISH
      signal was found also in interchromosomal connectives linking centromeres of non
      homologous chromosomes in mitotic cells. The presence of DNA in the connectives
      was confirmed by immunostaining with anti-dsDNA antibodies as well as in
      experiments on nick-translation and random primed labeling in situ. Non
      denaturing FISH with FCP probe and random primed labeling of non-denatured
      chromosomes resulted in fluorescence signal on both centromeres and
      intercentromeric connectives, thus providing evidence for the availability of
      single-strand DNA tracts in FCP sequence. It is suggested that the highly
      repeated FCP centromeric sequence may be respondible for interconnection of
      mitotic chromosomes and may by involved in nuclear architecture maintenance in
      the chaffinch.

PMID- 10953866
TI  - [Polymorphism of nucleolar organizer regions of chromosomes in human embryos].
AB  - NOR activity in metaphase chromosomes from extraembryonic and embryonic tissues
      of 9-12 week human fetuses was studied after standard silver staining.
      Significant interidividual variations in the average cummulative NOR activity was
      assessed by means of one-factor dispersion analysis. No significant intertissue
      fluctuation of NOR activity was found. Total number of NOR+ chromosomes
      demonstrated no correlation with the embryonic age. Steady growth of an average
      cummulative NOR activity respective of progressive embryonic age was proven by
      correlation analysis method. Unequal participation of NOR-bearing chromosomes of
      D- and G-groups during early embryonic development in human was shown.

PMID- 10953867
TI  - [Karyotype of the midge Chironomus heterodentatus Konstantinov from the group
      Obtusidens (Diptera, Chironomidae)].
AB  - The karyotype of Chironomus heterodentatus, belonging to the obtusidens-group
      described by Konstantinov from the Volga in 1956, was studied in detail.
      Combinations of chromosomal arms are AB, CD, EF and G (cytocomplex thummi). The
      Ch. heterodentatus karyotype cleary differs from those of other members of the
      obtusidens-group with a species-specific banding pattern in arms A, B, C and D.
      Chromosomal polymorphism on homo- and heterozygous inversions was found in arms,
      A, B, D, E and G. 19 inversion banding sequences and their 27 genotypic
      combinations have been recorded. The shortest arm G is highly polymorphic.
      Heterozygotes on the Balbiani ring activity were found in arm G along with homo-
      and heterozygotes on inversions. B-chromosomes with a frequency equal to 2.7
      25.0% were recorded in some Volga populations.

PMID- 10953868
TI  - [Tartrate-sensitive and tartrate-resistant acid phosphatases in Amoeba proteus].
AB  - In free-living Amoeba proteus (strain B), acid phosphatase (AcP) was examined by
      disc-electrophoresis in polyacrylamide gel. The tartrate-sensitive amebian AcP
      was greatly inhibited by dithiothreitol and Cu2+, and only partly inhibited by
      sodium orthovanadate, ammonium molybdate, EDTA, disodium salt and Mg2+, Ca2+,
      Zn2+ and Mn2+. On the contrary, it appeared to be resistant to sulfhydryl
      reagents--4(hydroxymercury) benzoic acid, sodium salt and N-ethylmaleimide.
      Unlike the tartrate-sensitive enzyme, the tartrate-resistant AcP was greatly
      inhibited by EDTA and partly inhibited by dithiothreitol, Mg2+ and Cu2+ (Mn2+ >
      Cu2+), being activated by orthovanadate, molybdate, sulfhydryl reagents, Mg2+,
      Ca2+ and Zn2+. Both tartrate-sensitive and tartrate-resistant AcPs lack
      apparently free SH-groups necessary for their catalytic activities. Using 2
      naphthyl phosphate as a substrate at pH 4.5, six AcP electromorphs were revealed
      in cytosol and sediment, four of these being most frequently localized in the
      former, and two in the latter. Two other AcP electromorphs were confined to the
      sediment only. Depending on the quantity of sedimented amoebae making a
      homogenate (0.5 or 2.0 cm3), that was added to Percoll solution, the lysosomal
      AcP fraction in polyacrylamide gel was represented by one or two tartrate
      sensitive electromorphs. Therefore, tartrate-resistant AcP in A. proteus may be a
      lysosomal enzyme, while tartrate-resistant AcP may correspond to serine/threonine
      protein phosphatase.

PMID- 10953869
TI  - Subarachnoid hemorrhage and cerebral vasospasm--facts and perspectives.

PMID- 10953870
TI  - Homocysteine--relevant for atherogenesis?
AB  - Numerous studies report strong associations between hyperhomocysteinemia and
      premature atherosclerotic vascular disease. Causes of hyperhomocysteinemia are
      hereditary heterozygous or, in very rare cases, homozygous defects, and quite
      frequently a lack of the coenzymes B6 and B12 and the cosubstrate folate.
      Lifestyle factors, age, sex, acute and chronic illness, vitamin deficiency and
      certain drugs may elevate homocysteine concentrations. Vitamin B supplementation,
      especially folic acid, is an effective treatment of hyperhomocysteinemia.
      Clinical trials are required to confirm the potential benefit of lowering
      homocysteine in regard of the development and progression of atherosclerotic
      vascular disease. The relevance of hyperhomocysteinemia as a risk factor for
      atherosclerosis, in contrast to the classical triad of risk factors, namely
      hypercholesterolemia, smoking and hypertension, is still unknown. Furthermore, a
      lack of standardized analytical methods for the determination of both
      homocysteine and blood folate renders the evaluation of studies and clinical data
      difficult. Therefore, at present, diagnosis and treatment is only recommended in
      high-risk patients (strong family history of premature atherosclerosis or
      arterial occlusive disease, especially in the absence of other risk factors, as
      well as in members of their families) with hyperhomocysteinemia.

PMID- 10953871
TI  - Sympathetic nervous system exclusion following experimental subarachnoid
      haemorrhage prevents vasospasm in rabbits.
AB  - BACKGROUND: The objective of this study was to establish whether the exclusion of
      the effect of the sympathetic nervous system prevents vasospasm of cerebral
      arteries after experimental subarachnoid haemorrhage in rabbits. METHODS: The
      effect of sympathetic exclusion on vasospasm was studied in 29 New Zealand
      rabbits under conditions similar to human subarachnoid haemorrhage: 1. The
      activity of the sympathetic nervous system was excluded only after subarachnoid
      haemorrhage. 2. The effect of this exclusion was evaluated on the eighth day
      after subarachnoid haemorrhage. 3. The single haemorrhage model of experimental
      subarachnoid haemorrhage was chosen. Four groups of rabbits were investigated.
      The control group A comprised rabbits without subarachnoid haemorrhage; group B
      consisted of those with subarachnoid haemorrhage (1 ml autologous blood/kg BW
      suboccipitally into the cisterna magna); group C included those with subarachnoid
      haemorrhage and pharmacological sympathetic exclusion by the alpha blocker
      phenoxybenzamine, and group D was composed of those with subarachnoid haemorrhage
      and operative sympathetic exclusion by cervical gangliectomy. Changes in the
      basilar arteries of rabbits were evaluated by computer image analysis, using
      histologic specimens of vessel walls. A new measuring procedure was developed to
      assess the intensity of vasospasm; the method has a corrugation coefficient that
      expresses changes in intimal corrugation. RESULTS: Comparison of control group A
      and group B in regard of vessel intima corrugation showed significantly less
      corrugated intima in group A (P = 0.0042). In comparison with group B,
      corrugation of the vessel intima in group C was less intense after sympathetic
      exclusion by phenoxybenzamine following subarachnoid haemorrhage (P = 0.00012).
      In comparison with group B, a reduced corrugation was also found in group D after
      sympathetic exclusion by upper cervical gangliectomy following subarachnoid
      haemorrhage (P = 0.0026). CONCLUSIONS: The results of the study suggest that
      exclusion of sympathetic nervous system activity in rabbits prevents vasospasm in
      circumstances similar to subarachnoid haemorrhage in man. Thus, the sympathetic
      nervous system could play a critical role in the development of vasospasm in
      subarachnoid haemorrhage.

PMID- 10953873
TI  - [Analysis of the migration of cementless all-metal hip endoprosthesis].
AB  - Since September 1997, 58 patients have received a newly developed all-metal hip
      prosthesis at the department of orthopaedic surgery, University Hospital Vienna.
      In a retrospective study, the migration profile of 26 acetabular components of
      these prostheses with all-metal cups was evaluated. A total of 25 patients (10
      men, 15 women, mean age 61 years) who had been operated on earlier than 11 months
      previously were studied. Indications included coxarthrosis (15), congenital
      dysplasia of the hip (7), post-traumatic coxarthrosis (3), and change of the
      implant due to infection (1). Twenty-three patients (7 men, 16 women; mean age 63
      years) with 25 metal-backed polyethylene implants and matched demographic data,
      indications and cup size, served as the group for comparison. The mean duration
      of follow-up for both groups was 14 months. For analysis of migration a modified
      version of Dickob's method for digital measurement of comparative hip radiographs
      was used. Measurements were performed three times by one examiner. Migration
      values of more than 2.0 mm were regarded as a sign of possible cup loosening.
      After 13 to 20 months the average migration was -0.10 mm in horizontal and 0.18
      mm in vertical direction for all-metal prostheses, and -0.20 mm horizontally and
      0.47 mm vertically for the other group. Mean migration values exceeded the
      critical limit of 2.0 mm in two patients in the all-metal group, one of whom also
      had clinical signs of cup loosening. The covariance analysis of the highest
      migration levels of each patient revealed no significant differences between the
      groups; the postoperative Harris hip score was 98 points (range, 93-100) in the
      all-metal group and 97 (range, 92-100) in the other. Provided metal is carefully
      processed and cups are initially stable, the all-metal implants have equivalent
      in-growth as expressed by the migration analysis, and thus constitute an
      alternative therapeutic modality without polyethylene components.

PMID- 10953872
TI  - [Unaltered homocysteine levels during simvastatin therapy].
AB  - Homocysteinemia is regarded as a risk factor for vascular disease. Several risk
      factors and diseases, but also various drugs, amongst them some lipid lowering
      medications, have been shown to increase plasma homocysteine concentrations. We
      therefore assessed the influence of simvastatin on plasma homocysteine levels in
      57 patients suffering from severe familial heterozygous hypercholesterolemia.
      After 1, 3 and 6 months of simvastatin therapy plasma homocysteine levels did not
      show any change compared to the levels before therapy. Males had typically higher
      homocysteine levels than females and concentrations in smokers were in most
      subgroups significantly higher than in non-smokers. No difference in patients
      taking either 20 or 40 mg simvastatin was apparent and no correlation to the
      lipid lowering action was found. These findings indicate that in contrast to a
      number of other lipid lowering agents, simvastatin does not affect plasma
      homocysteine levels.

PMID- 10953874
TI  - Continuous haemofiltration with r-hirudin (lepirudin) as anticoagulant in a
      patient with heparin induced thrombocytopenia (HIT II).
AB  - A 60-year-old man was admitted to the hospital with aortic dissection. An
      operative excision and replacement with a Y-graft was performed. Postoperatively
      he developed multiple organ dysfunction and required intermittent haemofiltration
      (anticoagulation with heparin). An ischemia of the left leg occurred at the third
      postoperative day. The initial platelet count was 99,000/microliter. Continuous
      haemofiltration (CVVH) was started three days later. Thrombotic obstructions of
      haemodialysis filters and catheters occurred frequently and heparin-induced
      thrombocytopenia (HIT II) was suspected. Antibodies against heparin were found in
      the HIPA test. Despite heparin free citrate dialysis and anticoagulation with
      danaparoid thrombotic obstructions of filters and catheters continued. Therefore
      the anticoagulation therapy during CVVH was changed to recombinant hirudin
      (lepirudin). Starting dose was a bolus of 0.01 mg/kg bw followed by the same
      amount as maintenance dose per hour. Anticoagulation was adjusted to an increase
      of aPTT (activated partial thromboplastin time) to 1.5-2 times its normal value.
      A dose of 0.005 mg/kg bw/h lepirudin was sufficient to maintain adequate
      anticoagulation. After changing to lepirudin no further catheter obstructions
      were observed and the platelets recovered slowly. Renal function improved and
      five weeks after admission endogenous creatinine clearance showed a value of 25
      ml/min. We conclude that lepirudin is an effective anticoagulant during CVVH in
      patients with HIT II. In partly permeable polysulfon filters a dose of 0.005
      mg/kg bw/h lepirudin is sufficient to maintain adequate anticoagulation.
      Monitoring anticoagulation by measuring the increase of aPTT (factor 1.5-2.0)
      seems to be safe. However, optimally the r-hirudin concentration should be
      measured directly using the Ecarin clotting time.

PMID- 10953875
TI  - Absence of F1-ATPase activity in Kluyveromyces lactis lacking the epsilon
      subunit.
AB  - The mitochondrial F1-ATPase is a multimeric enzyme, comprised of 3alpha, 3beta,
      gamma, delta and epsilon subunits, that is primarily responsible for the
      synthesis of ATP in eukaryotic cells. Recent work has shown that the F1 complex
      of the petite-negative yeast Kluyveromyces lactis, with specific mutations in the
      alpha, beta or gamma subunits, has a novel function that suppresses lethality
      caused by loss of mtDNA. Previously, genes for the four largest subunits of K.
      lactis F1 have been identified and characterised. In this study the gene coding
      for the epsilon-subunit of F1, KlATPepsilon, has been isolated and found to
      encode a polypeptide of 61 amino acids with only 32 residues identical to those
      in the protein from Sacharomyces cerevisiae. Strains carrying a null mutation of
      KlATPepsilon are respiratory deficient while the introduction of ATPepsilon from
      S. cerevisiae restores growth on non-fermentable carbon sources. In contrast to
      S. cerevisiae, K. lactis disrupted in ATPepsilon does not have a detectable F1
      related mitochondrial ATP hydrolysis activity, suggesting that the epsilon
      subunit plays a critical role in the formation of the catalytic sector of F1.
      With a disrupted KlATPepsilon, the rho degrees-lethality suppressor function of
      F1 carrying the atp2-1 and atp1-6 alleles is abolished. However, inactivation of
      the epsilon subunit does not eliminate the rho degrees-viable phenotype of the
      atp1-1, atp2-9, atp3-2 mutants. It is suggested that the absence of epsilon may
      effect the assembly or stability of F in the wild-type, atp 2-1 and atp1-6
      strains, whereas the defect can be suppressed by the atp1-1, atp2-9 and atp3-2
      mutations in the alpha, beta and gamma subunits respectively.

PMID- 10953876
TI  - Isolation and partial characterization of the Kluyveromyces lactis homologue of
      SKP1.
AB  - The SKP1 gene of Kluyveromyces lactis was isolated as a suppressor of a lethal
      temperature-sensitive mutation in the Saccharomyces cerevisiae CTF13 gene
      (Chromosome Transmission Factor 13). KlSKP1 was localized at chromosome V,
      adjacent to KlPAS3. A similar arrangement of the two genes is present in S.
      cerevisiae. Disruption of the KISKP1 gene was lethal, whereas overexpression of
      KlSKP1 lead to a decreased growth rate, to swollen and chain-forming cells with
      an increased DNA content, and to decreased plasmid stability. In both yeasts,
      promoter constructs lacking most of the purported binding sequence showed
      increased transcription levels of KlSKP1 in comparison to constructs with the
      entire promoter.

PMID- 10953877
TI  - Isolation and characterization of KIUBP2, a ubiquitin hydrolase gene of
      Kluyveromyces lactis that can suppress a ts-mutation in CBF2, a gene encoding a
      centromeric protein of Saccharomyces cerevisiae.
AB  - The Kluyveromyces lactis UBP2 gene was isolated as a suppressor of a temperature
      sensitive mutation in CBF2, a gene coding for a centromere-binding protein of
      Saccharomyces cerevisiae. The UBP genes are hydrolases than can cleave a
      ubiquitin moiety from a protein substrate. KlUBP2 is not essential for growth
      since a disruption of the KlUBP2 gene had little effect, except for a slight
      decrease in the growth rate. The stability of centromere-containing plasmids was
      not influenced either. In addition to KlUBP2, five S. cerevisiae genes involved
      in the ubiquitination pathway could suppress the ts-mutation in the CBF2 gene,
      namely UBA1, UBA2, UBP1, UBP2 and YUH1, although YUH1 was the only one that could
      do this like KlUBP2 from a single-copy plasmid. Surprisingly, these genes encode
      proteins with antagonistic activity as two, UBA1 and UBA2, are ubiquitin
      activating enzymes whereas the other three are de-ubiquitinating hydrolases.

PMID- 10953878
TI  - Recombination between divergent sequences leads to cell death in a mismatch
      repair-independent manner.
AB  - Homologous recombination is an important DNA repair mechanism in vegetative
      cells. During the repair of double-strand breaks, genetic information is
      transferred between the interacting DNA sequences, thus creating a gene
      conversion event. Gene conversion of a functional member of a gene family, which
      uses an inactive member (such as a pseudogene) as a template, might have
      deleterious consequences. It is therefore important for the cell to prevent
      recombination between divergent sequences. We have studied the repair of a double
      strand break by recombination in a haploid yeast strain carrying 99% identical
      alleles located on different chromosomes. The fate of the broken chromosome was
      followed in the whole cell population without imposing selective constraints. Our
      results show that all the cells were able to repair the broken chromosome by gene
      conversion. During the repair, the cells arrest in the cell cycle with a
      "dumbbell" configuration characteristic of G2/M-arrested cells. Surprisingly,
      although all the cells repaired the broken chromosome, 60% of them were unable to
      resume growth and to form colonies after the repair was completed. The low level
      of cell recovery was due to the 1% divergence between the alleles, but was not
      dependent on the function of the mismatch-repair system. Cell death, however,
      could be prevented by the presence of an alternative source of perfect homology
      located on a different chromosome.

PMID- 10953879
TI  - Meiotic double-strand breaks in Schizosaccharomyces pombe.
AB  - Meiotic DNA double-strand breaks (DSBs) are associated with recombination hot
      spots in the yeast Saccharomyces cerevisiae and are believed to initiate the
      process of recombination. Until now, meiosis-induced breaks have not been shown
      to occur regularly in other organisms. Here we show, by pulsed-field gel
      electrophoresis of DNA, that meiotic DSBs occur transiently in all three
      chromosomes of the fission yeast Schizosaccharomyces pombe. In a repair defective
      mutant, carrying a mutation in the RecA homolog gene rhp51, meiotic DSBs
      accumulate. In contrast to expectation from the genetic map of S. pombe, however,
      many chromosomal DNA molecules remain unbroken during meiosis.

PMID- 10953880
TI  - Characterization of hch, the Podospora anserina homolog of the het-c heterokaryon
      incompatibility gene of Neurospora crassa.
AB  - The het-c locus controls heterokaryon formation in Neurospora crassa. It is
      subject to balancing selection operating to maintain polymorphism at that locus
      in natural populations. We have isolated hch, the het-c homolog from the related
      species Podospora anserina (hch for het-c homolog), in order to determine if this
      gene also functions as a het gene in that species. The het-c and hch sequences
      are highly similar but differ in the region defining allele specificity in N.
      crassa het-c. Analysis of hch variability in 11 natural P. anserina isolates with
      different het genotypes revealed no polymorphism. This suggested that hch does
      not function as a het gene. However, heterologous expression of the N. crassa het
      cPA allele in P. anserina triggers a growth defect reminiscent of the het-c
      incompatibility reaction.

PMID- 10953881
TI  - Deletion of the MAT-2 mating-type gene during uni-directional mating-type
      switching in Ceratocystis.
AB  - Ceratocystis eucalypti is strictly heterothallic, with single ascospore strains
      representing one of two opposite mating types. Most other Ceratocystis species,
      including C. virescens, C. pinicola, and C. fimbriata, are homothallic. In the
      homothallic species, the MAT-2 strains are self-fertile, while MAT-1 strains are
      self-sterile and grow more slowly than MAT-2 strains. The current hypothesis is
      that self-fertility of MAT-2 strains is due to the deletion of the MAT-2 mating
      type gene, resulting in the expression of the MAT-1 mating type. These mutant MAT
      1 strains are able to cross with MAT-2 strains. Part of the MAT-2 mating-type
      gene in C. eucalypti, C. pinicola, and C. fimbriata was amplified using
      degenerate primers designed from the conserved MAT-2 HMG DNA-binding motif. The
      expected approximately 300-bp PCR products were cloned and sequenced. Specific
      primers were designed that amplified 210-bp fragments only in MAT-2 isolates of
      C. eucalypti, C. virescens, C. pinicola, and C. finbriata. These fragments were
      present in self-fertile field isolates and self-fertile progeny but were absent
      in the self-sterile (MAT-1) progeny from selfings of C. virescens, C. pinicola,
      and C. fimbriata, thus supporting the hypothesis that the MAT-2 mating-type gene
      is deleted during uni-directional mating-type switching. A Southern-blot analysis
      was performed to confirm the deletion of MAT-2 gene in self-sterile progeny. The
      DNA sequence data for the C. eucalypti MAT-2 mating-type gene was increased to
      1371-bp using TAIL-PCR and uneven PCR, representing a portion of the complete MAT
      2 gene DNA sequence.

PMID- 10953882
TI  - Compass of 47,787 cattle ESTs.
AB  - Comparative Mapping by Annotation and Sequence Similarity (COMPASS) has been
      demonstrated to be an effective approach for predicting the chromosome location
      of expressed sequence tags (ESTs) and other sequence-based markers on the basis
      of comparative mapping information. Herein, we describe the development and use
      of a computer program to execute the COMPASS strategy en masse. The program was
      used to identify orthologs and predict map locations of 47,787 cattle ESTs. Among
      these 47,787 ESTs, 30,097 had significant matches with sequences in the human
      UniGene database and 21,311 were annotated with human GB4 radiation hybrid
      mapping data. These sequences are contained within 9,956 and 6,295 individual
      human UniGene clusters, respectively. The putative human orthologs and predicted
      cattle chromosome locations of the 21,311 cattle ESTs with GB4 mapping data are
      provided in this report as a resource for the research community.

PMID- 10953883
TI  - In the academic game, a higher degree is the qualifying standard, and every paper
      is a personal best.

PMID- 10953884
TI  - Intercollegiate board for sport and exercise medicine.

PMID- 10953885
TI  - Postgraduate medical education: methodology.

PMID- 10953886
TI  - The role of a masters degree as part of higher training in sports and exercise
      medicine or why do a masters?

PMID- 10953887
TI  - Fellowship in Sports Medicine.

PMID- 10953888
TI  - The German situation.

PMID- 10953889
TI  - Sports and exercise medicine in Finland.

PMID- 10953890
TI  - Sports medicine education in Australia.

PMID- 10953891
TI  - Education Australian physiotherapists: striving for excellence in sport and
      exercise medicine.

PMID- 10953892
TI  - What is a sports medicine specialist? A pilot study.

PMID- 10953893
TI  - Sport and exercise medicine in undergraduate medical schools in the United
      Kingdom and Ireland.

PMID- 10953894
TI  - Effects of exercise on lymphocytes and cytokines.
AB  - OBJECTIVES: To review results on exercise induced changes in the immune system
      following strenuous and moderate exercise. METHODS: A literature search over the
      past 15 years was conducted using Medline and selected papers. RESULTS: After
      intense long term exercise, the immune system is characterised by concomitant
      impairment of the cellular immune system and increased inflammation. Thus low
      concentrations of lymphocytes, suppressed natural immunity, suppressed lymphocyte
      proliferation, and suppressed levels of secretory IgA in saliva are found
      simultaneously with high levels of circulating proinflammatory and
      antiinflammatory cytokines. The underlying mechanisms are multifactorial and
      include neuroendocrinological and metabolic factors. The clinical consequences of
      the exercise induced immune changes have not formally been identified, but the
      exercise effect on lymphocyte dynamics and immune function may be linked to the
      exercise effects on resistance to infections and malignancy and the cytokine
      response may be linked to muscle damage or muscle cell growth. CONCLUSIONS:
      Moderate exercise across the life span seems to increase resistance to upper
      respiratory tract infections, whereas repeated strenuous exercise suppresses
      immune function. It is premature to offer advice on nutrition to athletes in
      order to alter the exercise induced immunosuppression found after exercise.

PMID- 10953895
TI  - The menisci: basic science and advances in treatment.
AB  - Once described as a muscle remnant, and therefore treated with disrespect, the
      meniscus is now known to be a vital structure within the knee. Minimal partial
      meniscectomy performed arthroscopically, or meniscal repair when practical, have
      become the standard treatments. In spite of the advancements in understanding
      meniscal function and its preservation, much remains to be studied. In the
      future, availability of better repair techniques and the option of meniscal
      replacement with allograft or prosthetic menisci are expected to improve
      outcomes.

PMID- 10953896
TI  - A survey of the causes of sudden death in sport in the Republic of Ireland.
AB  - BACKGROUND: Sudden death in sport is rare, but when it occurs the effects are
      devastating. There have not been any reports to date describing the frequency and
      causes of sudden death in sport in the Republic of Ireland. AIM: To describe the
      incidence, possible causes, associated factors, and pathological findings in
      people who died while exercising in the Republic of Ireland in the 10 year period
      from January 1987 to December 1996. METHODS: All 49 regional coroners in the
      Republic of Ireland were approached and details on all cases of sudden death in
      sport from 1 January 1987 to 31 December 1996 were requested. A questionnaire was
      used to document age, sex, participating sport, previous symptoms, previous
      medical investigations, circumstances of death, and main pathological finding in
      all reported cases. RESULTS: Of the 49 coroners surveyed, 45 replied. A total of
      51 cases of sudden death in sport were identified. The median age was 48 (range
      15-78). Fifty of the deaths were of men. Golf was the most popular participating
      sport. In 42 cases, the pathological cause of death was atherosclerotic coronary
      artery disease. CONCLUSIONS: This is the first time the incidence of sudden death
      in sport in the Republic of Ireland has been described. The main cause of death
      in all age groups was atherosclerotic coronary artery disease.

PMID- 10953897
TI  - Five facts and five concepts for rehabilitation of mechanical low back pain.

PMID- 10953898
TI  - Promoting physical activity in general practice: a controlled trial of written
      advice and information materials.
AB  - OBJECTIVE: To investigate the impact of a simple written prescription for
      physical activity given by a general practitioner and the effect of supplementing
      this with mailed information materials about physical activity. METHODS: A
      controlled trial was conducted in 27 general practices in New South Wales,
      Australia. Subjects were sequential routine care patients between 25 and 65 years
      old. Controls (n = 386) were recruited first, and intervention subjects two weeks
      later. Intervention subjects were randomised to receive a prescription only (n =
      380) or a prescription plus a mailed booklet (n = 376). Self reported physical
      activity levels were measured by interview at baseline, 6-10 weeks, and seven to
      eight months. RESULTS: By intention to treat, the average changes in minutes of
      total physical activity did not differ significantly between the groups. Inactive
      people in the prescription plus supplementary booklet group were significantly
      more likely than controls to report an increase in their physical activity by at
      least 60 min/week after 6-10 weeks (odds ratio 1.58, 95% confidence interval 1.06
      to 2.35). No significant short term improvements in self reported activity were
      shown in the prescription only group. In the supplemented group, the proportion
      reporting an increase in physical activity to 3,344 kJ/week at 6-10 weeks was not
      significant, and neither intervention group showed significant increases in any
      of the outcome measures at seven to eight months by intention to treat. Treatment
      received analysis showed greater improvements in intervention groups, especially
      the prescription plus booklet group, in which the odds of inactive people in this
      group reporting increased activity became significant at seven to eight months.
      CONCLUSIONS: A prescription for physical activity from a general practitioner,
      supplemented by additional written materials, can lead to modest short term
      improvements in self reported physical activity levels among inactive patients. A
      prescription alone was found not to be effective.

PMID- 10953899
TI  - Stress reactivity to and recovery from a standardised exercise bout: a study of
      31 runners practising relaxation techniques.
AB  - OBJECTIVE: To compare the efficacy in runners of two relaxation techniques with
      regard to exercise reactivity and recovery after exercise. METHODS: Thirty one
      adult male runners were studied prospectively for six months in three groups
      practising either meditation (n = 11) or autogenic training (n = 11) or serving
      as controls (n = 10). Before and after the six months relaxation intervention,
      indicators of reactivity to exercise and metabolism after exercise (blood lactate
      concentration, heart rate (HR), and oxygen consumption (VO2)), were tested
      immediately after and 10 minutes after exercise. Resting HR was also assessed
      weekly at home during the trial. State anxiety was measured before and after the
      intervention. RESULTS: After the relaxation training, blood lactate concentration
      after exercise was significantly (p<0.01) decreased in the meditation group
      compared with the control group. No difference was observed in lactate responses
      between the autogenic training group and the control group. There were no
      significant differences among the groups with regard to HR, VO2, or levels of
      anxiety. CONCLUSION: Meditation training may reduce the lactate response to a
      standardised exercise bout.

PMID- 10953900
TI  - Bone mineral density and serum testosterone in chronically trained, high mileage
      40-55 year old male runners.
AB  - OBJECTIVES: To identify physical activity that is beneficial for the maintenance
      of bone strength with increasing age by examining the relation between bone
      mineral density (BMD) and chronic endurance training in men. BMD at the proximal
      femur, its subregions, and the lumbar spine, and serum testosterone were compared
      between two groups of long distance runners with more than 20 years of training
      experience and non-athletic controls. METHODS: Runners (n = 12) were divided into
      (a) high volume runners (n = 7), running 64-80 km a week, and (b) very high
      volume runners (n = 5), running more than 95 km a week, and compared with non
      athletic male controls, exercising in non-endurance oriented activities two to
      four times a week. BMD (g/cm2) at the total proximal femur, femoral neck,
      trochanteric region, and lumbar spine was measured by dual energy x ray
      absorptiometry. Total testosterone (nmol/l) and free testosterone (pmol/l) in
      serum were measured by radioimmunoassay from single fasting blood samples.
      RESULTS: Height, weight, and age (range = 40-55 years) were not significantly
      different between groups. The high volume runners had significantly higher BMD at
      the total proximal femur (1.09 (0.17) v 0.94 (0.056)), femoral neck (0.91 (0.16)
      v 0.78 (0.071)), and trochanteric region (0.85 (0.14) v 0.73 (0.053)) than
      controls (p<0.05). The differences in BMD for the proximal femur between the very
      high volume runners and the other two groups were not significant. There was no
      difference in lumbar spine BMD, total testosterone, or free testosterone between
      groups. However, there was a significant negative correlation between total
      testosterone (r = -0.73, p<0.01) and free testosterone (r = -0.79, p<0.005) and
      running volume in the distance runners. CONCLUSIONS: Long term distance running
      with training volumes less than 80 km a week had a positive effect on BMD of the
      proximal femur. With running volumes greater than 64 km a week, training was
      inversely related to testosterone levels, but levels remained within the normal
      range.

PMID- 10953901
TI  - Relation of anterior pelvic tilt during running to clinical and kinematic
      measures of hip extension.
AB  - BACKGROUND: Limited hip extension flexibility due to tight hip flexor musculature
      or anterior hip capsular and ligamentous structures is a possible cause of
      increased anterior tilt of the pelvis during running. However, to date, research
      exploring this relation, as well as the kinematic relation between anterior tilt
      of the pelvis and peak hip extension range of motion during running, is not
      available. OBJECTIVE: To assess the relation of anterior pelvic tilt during
      running to peak hip extension range of motion measured during running and hip
      extension flexibility measured clinically. METHODS: Hip extension flexibility was
      assessed using the Thomas test, and the three dimensional kinematic motion of the
      pelvis and hips were recorded using a VICON motion analysis system with 14 elite
      athletes running on a treadmill at 20 km/h. RESULTS: Anterior pelvic tilt
      displayed a significant (p<0.01) correlation with peak hip extension range of
      motion during running. Anterior pelvic tilt tended to be increased in runners who
      displayed reduced absolute peak hip extension range of motion during terminal
      stance. No significant correlation was shown for hip extension flexibility with
      either anterior pelvic tilt or peak hip extension range of motion during running.
      CONCLUSIONS: The outcomes of this study indicate that anterior pelvic tilt and
      hip extension are coordinated movements during running. Static hip extension
      flexibility measured using the modified Thomas test does not appear to be
      reflective of these dynamic movements.

PMID- 10953902
TI  - Dietary creatine supplementation does not affect some haematological indices, or
      indices of muscle damage and hepatic and renal function.
AB  - BACKGROUND: The use of creatine (Cr) as a nutritional supplement to aid athletic
      performance has gained widespread popularity among athletes. However, concerns
      have recently been expressed over potentially harmful effects of short and long
      term Cr supplementation on health. METHODS: Forty eight young healthy subjects
      were randomly allocated to three experimental protocols aimed at elucidating any
      potential health risks associated with five days (20 g/day) to nine weeks (3
      g/day) of Cr supplementation. Venous blood samples were collected before and
      after periods of Cr supplementation and were analysed for some haematological
      indices, and for indices of hepatic, muscular, and renal dysfunction. FINDINGS:
      All measured indices were well within their respective normal range at all times.
      Serum creatinine concentration tended to be increased the day after Cr
      supplementation. However, values had returned to baseline six weeks after the
      cessation of supplementation. These increases were probably attributable to
      increased creatinine production rather than renal dysfunction. No indication of
      impairment to the haematological indices measured, hepatic function, or muscle
      damage was apparent after Cr supplementation. INTERPRETATION: These data provide
      evidence that there are no obvious adverse effects of acute or more chronic Cr
      supplementation on the haematological indices measured, nor on hepatic, muscle,
      and renal function. Therefore there is no apparent health risk associated with Cr
      supplementation to healthy people when it is ingested in quantities that have
      been scientifically proven to increase muscle Cr stores.

PMID- 10953903
TI  - Factor XIIa and triacylglycerol rich lipoproteins: responses to exercise
      intervention.
AB  - OBJECTIVES: (a) To determine if factor XIIa (FXIIa) would be sensitive to change
      from exercise intervention in a group of previously sedentary/low active middle
      aged men and women; (b) to investigate further the previously reported relation
      between FXIIa and triacylglycerol (TAG) rich lipoproteins. METHODS: Thirty seven
      men (mean (SD) age 57 (7) years) and 60 women (mean age 54 (7) years) completed
      the study. Before the intervention, these subjects were randomly allocated to a
      group of walkers (n = 81) or controls (n = 16). Before and after an 18 week
      walking intervention, fasted blood samples were collected and analysed for FXIIa,
      TAG, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), and apolipoprotein (apo) B. RESULTS:
      Kruskal-Wallis analysis of data obtained before the intervention showed no
      significant differences (p>0.4) between the walking and control groups for age,
      height, body mass, gender, FXIIa, TAG, TC, HDL-C, or apo B, although the women
      did show significantly lower levels of TAG (p<0.04) and higher HDL-C (p<0.0001)
      than the men. General linear model analysis of data obtained after the
      intervention, using the baseline value as a covariate, showed significant
      reductions (p<0.0001) in FXIIa for the walkers compared with the controls.
      Pearson product-moment correlations also showed significant relations between the
      concentrations of FXIIa and TAG, TC, LDL-C, and apo B. CONCLUSIONS: The findings
      of this study suggest that FXIIa is sensitive to change from exercise
      intervention and support previous research showing an association between the
      concentrations of FXIIa and TAG rich lipoproteins.

PMID- 10953904
TI  - Decreasing landing forces: effect of instruction.
AB  - OBJECTIVE: To examine the effects of instructions related to joint kinematics,
      auditory stimuli, and imagery on lowering the vertical ground reaction forces
      associated with landing from a jump. STUDY DESIGN: Randomised controlled trial.
      SETTING: A laboratory in an educational institution. SUBJECTS: Eighty
      asymptomatic subjects (27 men) with a mean age of 24 years. INTERVENTION:
      Subjects were randomly assigned to the following groups: (1) instruction (limb
      position instructions); (2) auditory cue (listen to impact sounds); (3) imagery
      (metaphorical); (4) control. Subjects were required to jump from a box 300 mm in
      height and land on a force plate. Measures of the ground reaction force were
      recorded before and after the intervention. MAIN OUTCOME MEASURE: The peak
      vertical ground reaction force recorded at footstrike. RESULTS: The peak vertical
      ground reaction forces in the technical instruction and auditory groups were
      significantly less than those of the control group. There was no significant
      difference between the auditory and technical instruction groups. There was no
      significant difference between the imagery and control groups. CONCLUSIONS: When
      an aim of a rehabilitation programme is to minimise forces on the lower limb
      during landing type activities, the findings support the use of instructions
      related to kinematics as well as instructions that draw the patient's attention
      to the sound at impact.

PMID- 10953905
TI  - Ratings of perceived exertion in braille: validity and reliability in production
      mode.
AB  - OBJECTIVES: (a) To assess the validity and reliability of producing and
      reproducing a given exercise intensity during cycle ergometry using a braille
      version of Borg's standard 6-20 rating of perceived exertion (RPE) scale, and (b)
      to determine whether the exercise responses of blind participants, at a given
      produced RPE, were similar to those reported in recognised guidelines for sighted
      subjects. METHODS: Ten healthy registered blind volunteer participants (four
      women, six men; mean (SD) age 23.2 (9.0) years) performed an initial graded
      exercise cycle test to determine maximal heart rate (HRMAx) and maximal oxygen
      uptake (VO2MAX). Three trials of three exercise bouts at RPEs 9, 11, and 13 were
      then performed in random order on three separate days of the same week, with
      expired air and heart rate measured continuously. Each exercise bout was followed
      by 10 minutes of rest. The validity of the scale as a means of producing
      different exercise intensities was assessed using a two factor (RPE x trial)
      repeated measures analysis of variance. Intertrial reliability was assessed using
      intraclass correlation coefficients (ICC) and the bias +/-95% limits of agreement
      (95%LoA) procedure. RESULTS: Participants reported no difficulty in using the
      braille RPE scale. When asked to produce exercise intensities equating to RPE 9,
      11, and 13, they elicited mean %VO2MAX values of 47%, 53%, and 63% respectively.
      Analysis of variance showed no significant differences in either %HRMAx or
      %VO2MAX between trials at each of the three RPEs, but there was a significant
      difference (p<0.001) in both %HRMAx and %VO2MAX between the three RPE levels. All
      pairwise comparisons of the three different RPEs were significantly different
      (p<0.016). The ICC between the second and third trial for %HRMAx was significant
      (p <0.05) for all three RPEs. Similarly for %VO2MAX, the ICC was significant for
      RPE 9 and 11 but not 13. The 95%LoA decreased for both %HRMAx and %VO2MAX with
      each successive trial. CONCLUSIONS: Blind participants were successful in using a
      braille RPE scale to differentiate exercise intensity on a cycle ergometer. In
      every trial at RPE 13, all participants achieved %HRMAX and %VO2MAX levels, which
      fell within the recommendedrange for developing cardiorespiratory fitness. Using
      %HRMAx as a judge of intertrial reliability, the participants were able to repeat
      similar exercise intensities after two trials at each of the three RPEs (9,
      11,13). The same was true for RPE 9 and 11, when %VO2MAX was used as a judge, but
      further trials were required to achieve similar reliability at RPE 13. A braille
      RPE scale can be used by healthy blind people during cycle ergometry, with
      similar effect to the visual analogue scale recommended for use in healthy
      sighted people.

PMID- 10953906
TI  - Physiological and anthropometric characteristics of amateur rugby league players.
AB  - OBJECTIVES: To investigate the physiological and anthropometric characteristics
      of amateur rugby league players. METHODS: Thirty five amateur rugby league
      players (19 forwards and 16 backs) were measured for height, body mass,
      percentage body fat (sum of four skinfolds), muscular power (vertical jump),
      speed (10 m and 40 m sprint), and maximal aerobic power (multistage fitness
      test). Data were also collected on match frequency, training status, playing
      experience, and employment related physical activity levels. RESULTS: The 10 m
      and 40 m sprint, vertical jump, percentage body fat, and multistage fitness test
      results were 20-42% poorer than previously reported for professional rugby league
      players. Compared with forwards, backs had significantly (p<0.01) lower body mass
      (79.7 (74.7-84.7) kg v 90.8 (86.2-95.4) kg) and significantly (p<0.01) greater
      speed during the 40 m sprint (6.45 (6.35-6.55) v 6.79 (6.69-6.89) seconds).
      Values for percentage body fat, vertical jump, 10 m sprint, and maximal aerobic
      power were not significantly different (p>0.05) between forwards and backs. When
      compared with professional rugby league players, the training status of amateur
      rugby league players was 30-53% lower, with players devoting less than three
      hours a week to team training sessions and about 30 minutes a week to individual
      training sessions. The training time devoted to the development of muscular power
      (about 13 minutes a week), speed (about eight minutes a week), and aerobic
      fitness (about 34 minutes a week) did not differ significantly (p>0.05) between
      forwards and backs. At the time of the field testing, players had participated,
      on average, in one 60 minute match every eight days. CONCLUSIONS: The
      physiological and anthropometric characteristics of amateur rugby league players
      are poorly developed. These findings suggest that position specific training does
      not occur in amateur rugby league. The poor fitness of non-elite players may be
      due to a low playing intensity, infrequent matches of short duration, and/or an
      inappropriate training stimulus.

PMID- 10953907
TI  - Anabolic steroid accelerated multicompartment syndrome following trauma.
AB  - The case is reported of a 23 year old male body builder who was involved in a
      road traffic accident after taking anabolic steroids. The resulting trauma caused
      a severe life threatening acute multicompartment syndrome resulting in the need
      for urgent multiple fasciotomies.

PMID- 10953908
TI  - Traumatic priapism: an unusual cycling injury.
AB  - A case is reported of a 35 year old man who sustained an injury to the perineum
      in a cycling accident which resulted in a traumatic priapism. After confirmation
      of the diagnosis by Doppler sonography and angiography, therapeutic selective
      arterial embolisation was followed by successful detumescence of the penis and
      subsequent return of normal erectile function. It is suggested that percutaneous
      embolisation of the lacerated cavernosal artery is a safe and effective minimally
      invasive treatment for this uncommon condition.

PMID- 10953909
TI  - Potentially reversible causes of non-ventricular fibrillation/ventricular
      tachycardia (VF/VT).

PMID- 10953910
TI  - Survey of sports injury prevention programmes in the European Community.

PMID- 10953911
TI  - Use of imaging data for predicting clinical outcome.

PMID- 10953912
TI  - Denial of mental illness in athletes.

PMID- 10953913
TI  - Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or
      inflammatory cytokine inhibitors.
AB  - Gene therapy offers advantages for the immunotherapeutic delivery of cytokines or
      their inhibitors. After gene transfer, these mediators are produced at relatively
      constant, non-toxic levels and sometimes in a tissue-specific manner, obviating
      limitations of protein administration. Therapy with viral or nonviral vectors is
      effective in several animal models of autoimmunity including Type 1 diabetes
      mellitus (DM), experimental allergic encephalomyelitis (EAE), systemic lupus
      erythematosus (SLE), colitis, thyroiditis and various forms of arthritis. Genes
      encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most
      frequently protective. Autoimmune/ inflammatory diseases are associated with
      excessive production of inflammatory cytokines such as IL-1, IL-12, tumor
      necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). Vectors
      encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble
      IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc
      fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or
      EAE. We use intramuscular injection of naked plasmid DNA for cytokine or
      anticytokine therapy. Muscle tissue is accessible, expression is usually more
      persistent than elsewhere, transfection efficiency can be increased by low
      voltage in vivo electroporation, vector administration is simple and the method
      is inexpensive. Plasmids do not induce neutralizing immunity allowing repeated
      administration, and are suitable for the treatment of chronic immunological
      diseases.

PMID- 10953914
TI  - Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by
      adenovirus-mediated expression of the klotho gene.
AB  - BACKGROUND: We have established a novel mouse mutant, klotho (kl), by insertional
      mutation of a transgene and identified the structural gene. The mouse homozygous
      for the mutation exhibits multiple pathological conditions resembling age-related
      disorders in humans and can be regarded as a model of human premature aging
      syndromes. However, the pathophysiological role of Klotho protein has not been
      clarified. METHODS: A replication-deficient adenoviral vector expressing the
      membrane form of the mouse klotho gene was constructed and we examined Klotho
      expression in vitro. The recombinant adenoviral vector was then administered
      intravenously into klotho mice at 4-5 weeks of age and its therapeutic potential
      was examined. RESULTS: Expression of Klotho protein was observed in the
      adenoviral vector-infected CHO cells. The klotho mice infused with the
      recombinant adenovirus showed a significant extension of life span and gain in
      body weight at 1 week after treatment. Macroscopic and histological analyses
      demonstrated the improvement of multiple pathological findings such as
      restoration from atrophy and cell formation and differentiation in the gonadal
      cells, immune tissues and subcutaneous fat. CONCLUSION: We showed that local
      expression of the klotho gene retards or partially improves pathological
      abnormalities in several organs of klotho mice after onset of the phenotypes.
      Therefore, the recombinant adenovirus vector will provide an important tool for
      investigating the molecular mechanism of the Klotho protein and give clues to
      understanding the individual disease mechanisms.

PMID- 10953915
TI  - Comparison of bicistronic retroviral vectors containing internal ribosome entry
      sites (IRES) using expression of human interleukin-12 (IL-12) as a readout.
AB  - BACKGROUND: Many gene therapy applications require the co-ordinated delivery of
      more than one reading frame. We wished to systematically compare IRES in the
      context of a retroviral vector to determine which was the most effective for
      protein production and viral titre. To do this we monitored expression of IL-12,
      as co-ordinated expression of both p35 and p40 subunits is required for
      production of the active heterodimer. METHODS: Retroviral vectors were
      constructed to express human IL-12 in which an IRES initiates translation of the
      p40 subunit, with the IRES optimally aligned to the initiation codon of p40.
      Vectors containing an IRES from either polio virus (PV), encephalomyocarditis
      virus (EMCV), foot and mouth disease virus (FMDV) or murine leukaemia virus (MLV)
      were compared with a vector expressing IL-12 as a single protein (Flexi-12; in
      which the two IL-12 subunits are linked by a peptide). RESULTS: All vectors
      produced high titre virus and directed synthesis of IL-12 in target cells. The
      bicistronic vectors containing the IRES from EMCV and PV were the most effective
      in infected 3T3 cells, producing up to 40 ng IL-12/10(6) cells/48 h, similar to
      the 50 ng IL-12/10(6) cells/48 h obtained with Flexi-12. The IRES from PV was the
      most efficient in human melanoma cells. CONCLUSIONS: Bicistronic retroviral
      vectors have been constructed that effectively transduce target cells and produce
      high levels of protein. Target cell specificity of IRES function was observed.
      The combination of Flexi-12 and the IRES from PV will be useful in the generation
      of vectors expressing IL-12 with a second protein such as IL-2 for transduction
      of melanoma cells.

PMID- 10953916
TI  - Multiply deleted [E1, polymerase-, and pTP-] adenovirus vector persists despite
      deletion of the preterminal protein.
AB  - BACKGROUND: The inherent limitations of [E1-]Ad vectors as gene therapy vehicles
      suggest that further modifications may improve their overall performance
      profiles. However, Ad vector modifications can have untoward effects on their
      basic biology, e.g., some helper-virus dependent Ad vectors have been found to be
      unstable without the presence of preterminal protein (pTP) activities. Despite
      this concern, we generated a new class of helper-virus independent Ad vector that
      was multiply deleted for the E1, polymerase, and pTP genes, and investigated the
      ramifications of these deletions upon several vector performance parameters.
      METHODS: The construction and propagation of an [E1-, polymerase-, pTP-]Ad vector
      was achieved with the use of trans-complementing cells co-expressing the Ad E1,
      polymerase and pTP genes. RESULTS: High titer production of the [E1-, polymerase
      , pTP-]Ad vector was successfully accomplished via conventional Ad purification
      techniques. This unique class of Ad vector was capable of long-term gene transfer
      in vivo (despite lacking pTP functions) that was concomitant with a significantly
      decreased hepatic toxicity. CONCLUSIONS: Previous studies had suggested that Ad
      genome persistence in vivo may be dependent upon the presence of low level vector
      genome replication and/or pTP functions. Our results suggest that [E1-,
      polymerase-, pTP-]Ad vectors can overcome these barriers. The further benefits
      afforded by the use of this class of Ad vector (increased cloning capacity, high
      level growth, decreased propensity to generate replication competent Ad (RCA),
      decreased toxicity) suggests that they will be highly beneficial for use in
      several aspects of human gene therapy.

PMID- 10953917
TI  - Efficient recombinant adeno-associated virus production by a stable rep-cap HeLa
      cell line correlates with adenovirus-induced amplification of the integrated rep
      cap genome.
AB  - BACKGROUND: A possible procedure for the production of clinical grade recombinant
      adeno-associated virus type 2 (rAAV) would include the use of packaging cell
      lines, harboring the rep-cap genes and the vector, combined with a replication
      defective adenoviral plasmid to provide the helper activities. Several studies
      have already shown that rAAV can be efficiently assembled by infecting the stable
      packaging cell line with adenovirus. However, the direct comparison with an
      adenoviral plasmid has never been reported. METHODS: To investigate this point, a
      clone of HeLa and 293 cells harboring one to two rep-cap copies per cell genome
      (HeRC32 and 293RC21, respectively) were generated. Recombinant AAV was produced
      by transiently transfecting the AAVCMVLacZ vector and supplying the adenoviral
      helper activities by either wild-type adenovirus or an adenoviral plasmid (pAdc).
      As a control, rAAV was similarly produced from naive Hela and 293 cells
      additionally transfected with a rep-cap plasmid. RESULTS: Despite satisfactory
      rAAV yields from Hela and 293 cells, we show that those from HeRC32 and 293RC21
      cells dramatically decrease when adenovirus is replaced by the adenoviral plasmid
      (pAdc). The analysis performed to identify the factors hampering efficient rAAV
      assembly by HeRC32 cells in the presence of pAdc shows that: (1) while upon
      adenovirus infection the integrated rep-cap genome undergoes a dramatic
      amplification leading to a 100-fold increase in the rep-cap copy number, no
      amplification is detected upon transfection of pAdc; (2) in pAdc-transfected
      HeRC32 cells, the intracellular localization of the adenovirus E4orf6 and E1B
      55kDa proteins is abnormal as compared to adenovirus-infected cells. CONCLUSIONS:
      This study documents that stable rep-cap cells lines are severely hampered for
      rAAV assembly when a replicative adenovirus is substituted with an adenoviral
      plasmid. Furthermore, our results also suggest that the lack of amplification of
      the rep-cap genes, eventually combined with the altered distribution of the
      adenoviral proteins, E4orf6 and E1B-55kDa, is related to the low rAAV yields
      observed under these conditions.

PMID- 10953918
TI  - In vivo gene delivery to the lung using polyethylenimine and fractured
      polyamidoamine dendrimers.
AB  - BACKGROUND: Gene transfer into the airways could be of importance for the
      treatment of chronic lung diseases such as cystic fibrosis. In the past few years
      several attempts have been made to effectively deliver DNA to the lung using
      different viral and non-viral vector systems. Viral vectors and cationic lipids
      have been tested intensively but the properties of cationic polymers such as
      polyethylenimine (PEI) 25 kDa and fractured polyamidoamine dendrimers to deliver
      DNA to the airways have not been studied. Surfactant preparations have been shown
      to influence pulmonary adenoviral and naked plasmid DNA mediated gene transfer in
      vivo. We investigated the gene delivery efficiency of branched PEI 25 kDa and
      fractured dendrimers to the murine lung in vivo and also examined the effect of
      surfactant on PEI 25 kDa mediated gene transfer to the lung. METHODS: Cationic
      polymer/DNA complexes were prepared in 25 mM HEPES buffer (pH = 7.4) or double
      distilled water and administered to the lungs of BALB/c mice via cannula
      intubation. The trachea, left and right lung, heart, liver and esophagus were
      examined for luciferase activity. Inflammation was assessed by performing
      standard histology. RESULTS: PEI/DNA complexes showed a high level of luciferase
      gene expression in the lung. Complexes formed in double distilled water exhibited
      higher gene expression than complexes formed in 25 mM HEPES buffer (pH 7.4). The
      optimal N/P ratio was found to be N/P = 10 in double distilled water. Luciferase
      activity was only detected in the lung and decreased rapidly in a time-dependent
      manner. The addition of a natural surfactant preparation, Alveofact, slightly
      reduced gene transfer of branched PEI 25 kDa. Luciferase gene expression obtained
      by using fractured dendrimers was very low. CONCLUSION: The present study
      demonstrates that PEI 25 kDa, but not polyamidoamine dendrimers, effectively
      mediates transient gene transfer to the murine lung after intratracheal
      intubation. In conclusion, branched PEI 25 kDa was found to be an effective
      vector for pulmonary gene delivery in vivo, being superior to fractured
      dendrimers.

PMID- 10953919
TI  - Induction of angiogenesis by implantation of encapsulated primary myoblasts
      expressing vascular endothelial growth factor.
AB  - BACKGROUND: We previously demonstrated that intramuscular implantation of primary
      myoblasts engineered to express vascular endothelial growth factor (VEGF)
      constitutively resulted in hemangioma formation and the appearance of VEGF in the
      circulation. To investigate the potential for using allogeneic myoblasts and the
      effects of delivery of VEGF-expressing myoblasts to non-muscle sites, we have
      enclosed them in microcapsules that protect allogeneic cells from rejection, yet
      allow the secretion of proteins produced by the cells. METHODS: Encapsulated
      mouse primary myoblasts that constitutively expressed murine VEGF164, or
      encapsulated negative control cells, were implanted either subcutaneously or
      intraperitoneally into mice. RESULTS: Upon subcutaneous implantation, capsules
      containing VEGF-expressing myoblasts gave rise to large tissue masses at the
      implantation site that continued to grow and were composed primarily of
      endothelial and smooth muscle cells directly surrounding the capsules, and
      macrophages and capillaries further away from the capsules. Similarly, when
      injected intraperitoneally, VEGF-producing capsules caused significant localized
      inflammation and angiogenesis within the peritoneum, and ultimately led to fatal
      intraperitoneal hemorrhage. Notably, however, VEGF was not detected in the plasma
      of any mice. CONCLUSIONS: We conclude that encapsulated primary myoblasts persist
      and continue to secrete VEGF subcutaneously and intraperitoneally, but that the
      heparin-binding isoform VEGF164 exerts localized effects at the site of
      production. VEGF secreted from the capsules attracts endothelial and smooth
      muscle cells in a macrophage-independent manner. These results, along with our
      previous results, show that the mode and site of delivery of the same factor by
      the same engineered myoblasts can lead to markedly different outcomes. Moreover,
      the results confirm that constitutive delivery of high levels of VEGF is not
      desirable. In contrast, regulatable expression may lead to efficacious, safe, and
      localized VEGF delivery by encapsulated allogeneic primary myoblasts that can
      serve as universal donors.

PMID- 10953921
TI  - Gene therapy of severe combined immunodeficiency. Interview with Alain Fischer.

PMID- 10953920
TI  - The growth inhibition of hepatoma by gene transfer of antisense vascular
      endothelial growth factor.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent mediator of
      angiogenesis and tumor growth in solid tumors. Therefore, to induce tumor
      regression, antiangiogenic agents to block VEGF need to be administered
      repeatedly. METHOD: We constructed the recombinant mammalian expression vector
      bearing an antisense-VEGF cDNA, pZeoVEGFa. We examined the effect of pZeoVEGFa on
      the growth of SK-HEP1 hepatoma cells, bovine capillary endothelial (BCE) cells,
      and tubule formation of BCE cells in fibrin gel. To evaluate the function of
      pZeoVEGFa in vivo, we implanted SK-HEP1 hepatoma cells subcutaneously into nude
      mice. RESULTS: In SK-HEP1 hepatoma cells, we showed that the synthesis of VEGF
      protein was suppressed by the stable and transient transfection of pZeoVEGFa.
      pZeoVEGFa inhibited the proliferation of BCE cells and significantly suppressed
      tubule formation of BCE cells. pZeoVEGFa inhibited a morphological change from a
      round shape to an elongated spindle shape in fibrin gel. When pZeoVEGFa was
      injected peritumorally by liposomes, tumor growth was inhibited. CONCLUSION:
      Endothelial cell proliferation, tubule formation and tumor growth may be
      diminished by down-regulation of endogenous VEGF expression in tumor cells or
      tissue. These findings indicate that the efficient down-regulation of the VEGF
      produced by tumor cells using antisense strategies has an antitumor effect. We
      suggest that VEGF-targeted antiangiogenic gene therapy could be an effective
      strategy to treat VEGF-producing tumors.

PMID- 10953923
TI  - The construct of resilience: a critical evaluation and guidelines for future
      work.
AB  - This paper presents a critical appraisal of resilience, a construct connoting the
      maintenance of positive adaptation by individuals despite experiences of
      significant adversity. As empirical research on resilience has burgeoned in
      recent years, criticisms have been levied at work in this area. These critiques
      have generally focused on ambiguities in definitions and central terminology;
      heterogeneity in risks experienced and competence achieved by individuals viewed
      as resilient; instability of the phenomenon of resilience; and concerns regarding
      the usefulness of resilience as a theoretical construct. We address each
      identified criticism in turn, proposing solutions for those we view as legitimate
      and clarifying misunderstandings surrounding those we believe to be less valid.
      We conclude that work on resilience possesses substantial potential for
      augmenting the understanding of processes affecting at-risk individuals.
      Realization of the potential embodied by this construct, however, will remain
      constrained without continued scientific attention to some of the serious
      conceptual and methodological pitfalls that have been noted by skeptics and
      proponents alike.

PMID- 10953924
TI  - The odds of resilience.
AB  - This article presents sample research designs for the investigation of questions
      concerning resilience. Sample hypothesis from specific research designs are
      described in the form of odds ratios.

PMID- 10953925
TI  - Some thoughts about resilience versus positive development, main effects versus
      interactions, and the value of resilience.
AB  - Interaction effects are the defining feature of resilience and resilience
      research and are responsible for the unique contributions of this field of study
      to our understanding of human development. The methodological and statistical
      challenges posed by interaction effects do not, by themselves, undermine the
      value of resilience as a construct.

PMID- 10953926
TI  - Are there implications for prevention research from studies of resilience?
AB  - In this commentary, the question is raised whether prevention research can
      benefit from resilience research in designing interventions. Although many areas
      in the investigative interests of prevention and resilience researchers overlap,
      Luthar, Cicchetti, and Becker may have set the bar too high for defining
      resilience in the context of varying levels of adversity.

PMID- 10953928
TI  - Extended visual fixation in the early preschool years: look duration, heart rate
      changes, and attentional inertia.
AB  - Visual fixation in infants from 6 months to 2 years of age was examined for its
      fit to the theory of "attentional inertia." A children's movie ("Sesame Street"
      movie, "Follow that Bird") or an extended audiovisual stimulus (computer
      generated patterns) was presented to 40 children for a minimum of 20 min while
      fixation was videotaped and heart rate (HR) was recorded. Consistent with
      attentional inertia theory, fixations toward the stimuli had a lognormal
      distribution, HR decreased over the course of a look, and HR returned to
      prestimulus levels immediately before look offset. Older children (18 months, 24
      months) showed a distinction in the parameters describing the lognormal
      distribution for the "Sesame Street" movie and the audiovisual patterns, whereas
      younger children (6 months, 12 months) responded similarly to the two stimulus
      types. Fixation patterns of children in this age range suggest attention
      increases over the course of a look, and parameters consistent with attentional
      inertia theory differentially develop in this age range.

PMID- 10953927
TI  - The development of infants' reaches for stationary and moving targets.
AB  - The organization of infants' reaching skill for stationary and moving targets was
      examined. While 58 term, healthy infants at 5.5, 8.5, and 11.5 months of age
      reached for and grasped a cloth-covered dowel, their reaches were videotaped for
      later slow-motion analysis. Analyses addressed infants' anticipatory adjustment
      of hand alignment, use of information from spinning and oscillating targets to
      update ongoing reaches, and ability to capture targets moving in depth. Infants
      at all ages made anticipatory adjustments of hand alignment, although the
      effectiveness of these adjustments improved with age. Regardless of age, infants
      also used dynamic information from spinning and oscillating targets to update
      ongoing reaches, but the way infants used this information was related to age.
      Developmental constancy characterized infants' reaches for approaching targets.
      By observing infants' reaches for stationary, spinning, and approaching targets,
      the study expands the range of conditions under which adaptive reaching skill has
      been examined and provides insight into the roles of anticipation and updating in
      the development of early manual skill.

PMID- 10953930
TI  - The development of word retrieval abilities in the second year and its relation
      to early vocabulary growth.
AB  - The present research investigated the development of word retrieval abilities
      late in the second year when most children display a marked increase in word
      production. When asked what was hidden in a given box, children with still quite
      limited productive vocabularies were reliably less likely to produce the labels
      of the hidden objects than were children with larger productive vocabularies even
      though (1) all children could name those objects and (2) all children did well
      when asked to find those same hidden objects. Additionally, the provision of
      pictorial cues facilitated word retrieval, especially in the early stage of
      lexical development. Naming errors during a naturalistic book-reading session
      peaked in children whose productive vocabularies had recently begun to expand,
      further suggesting that word retrieval processes undergo significant changes at
      this time.

PMID- 10953929
TI  - Relations between drawing cubes and copying line diagrams of cubes in 7- to 10
      year-old children.
AB  - Previous research has suggested both links and differences between children's
      copying of line diagrams and their drawings of solid objects. If the diagram
      represents a familiar object, children make more errors than when copying a
      diagram of a nonobject or unfamiliar object, as if they are drawing from their
      representation of the object rather than copying the surface features of the
      diagram. However, copying a diagram yields fewer and different types of errors
      than drawing the equivalent solid, which suggests a different process. In
      Experiment 1 (n = 72), possible relations between copying and drawing are
      investigated by asking children to draw a solid cube, then to copy or trace a
      line diagram of the cube in oblique projection, and finally to draw the solid
      again. Copying was better than drawing, and there was positive transfer to a
      subsequent drawing. Tracing was very accurate, but transfer to drawing did not
      occur, possibly because of the automatic nature of tracing. In Experiment 2 (n =
      120) different groups received versions of the copying task that differed in the
      extent to which temporal order of line copying was structured. Asking children to
      copy the lines in a systematic order led to improved copies, but this performance
      did not carry over to a subsequent drawing of the solid. In contrast, when
      temporal ordering of line copying was not manipulated, there was positive
      transfer from copying to the subsequent drawing. In Experiment 3 (n = 80),
      provision of structure that emphasized faces by color-groupings of lines or
      coloring faces led to improved copies and did not hinder transfer to drawing the
      solid. Experiment 4 (n = 90) showed that in a solid drawing task emphasis on
      faces but not edges produced a positive effect, both on the immediate drawing and
      on a subsequent drawing of a plain cube. We conclude that emphasis on order of
      line copying improves performance in a copying task because in that case line-to
      line matching is an important element of the skill, whereas this does not aid
      drawing of the solid object, in which the focus is primarily on representation of
      faces and their interrelations.

PMID- 10953931
TI  - Basic level object categories support the acquisition of novel adjectives:
      evidence from preschool-aged children.
AB  - Two experiments examined 3- and 4-year-old children's ability to map novel
      adjectives to object properties. Sixty-four children were introduced to a target
      (e.g., a bumpy object), and asked to choose between (1) a matching test object
      (e.g., a different bumpy object), and (2) a contrasting test object (e.g., a
      smooth object). Four-year-olds successfully extended novel adjectives from the
      target to the matching test object whether these objects were drawn from the
      same, or different, basic level categories. In contrast, 3-year-olds' extensions
      were more restricted. They successfully extended novel adjectives if the target
      and test objects were drawn from the same basic level category but failed to do
      so if the objects were drawn from different basic level categories (Experiment
      1). However, if 3-year-olds (n = 20) were first permitted to extend a novel
      adjective to objects within the same basic level category, they were subsequently
      able to extend that novel adjective broadly to objects from different basic level
      categories (Experiment 2). Thus, basic level object categories serve as an
      initial foundation in the process of mapping novel adjectives to object
      properties.

PMID- 10953932
TI  - Buy low, sell high: the development of an informal theory of economics.
AB  - Two experiments were conducted to examine the development of economic
      understanding among 5-, 7-, and 9-year-olds (n = 31, 29, and 32, respectively).
      Most 5-year-olds exhibited understanding of the goal of acquiring desired goods
      but not of the goals of seeking profits, acquiring goods inexpensively, or
      competing successfully with other sellers. In contrast, most 7-year-olds and a
      large majority of 9-year-olds showed understanding of all of these concepts. The
      older children's understanding of these key concepts and the relations among them
      suggested that they had constructed an informal theory of economics,
      qualitatively different from the psychologically based understanding of the 5
      year-olds. Increased information-processing skills appeared to be among the
      sources of this new understanding.

PMID- 10953933
TI  - The stability of attachment security from infancy to adolescence and early
      adulthood: general introduction.
AB  - Current attachment theory hypothesizes that attachment security during infancy
      influences individual differences in adult representations of attachment. We
      present three long-term longitudinal studies using three different samples
      relevant to this hypothesis. Each study assesses infant attachment by using the
      Ainsworth Strange Situation and adult attachment by using the Berkeley Adult
      Attachment Interview (AAI). Attachment security was significantly stable in the
      first two studies. Discontinuity in all three studies was related to negative
      life events and circumstances. Comparison of the results across these
      complementary studies affords a degree of replication and sheds light on
      alternative interpretations. Various mechanisms underlying the stability and
      instability of attachment security are discussed.

PMID- 10953934
TI  - Attachment security in infancy and early adulthood: a twenty-year longitudinal
      study.
AB  - Sixty White middle-class infants were seen in the Ainsworth Strange Situation at
      12 months of age; 50 of these participants (21 males, 29 females) were
      recontacted 20 years later and interviewed by using the Berkeley Adult Attachment
      Interview (AAI). The interviewers were blind to the participants' Strange
      Situation classifications. Overall, 72% of the infants received the same secure
      versus insecure attachment classification in early adulthood, K = .44, p < .001.
      As predicted by attachment theory, negative life events-defined as (1) loss of a
      parent, (2) parental divorce, (3) life-threatening illness of parent or child
      (e.g., diabetes, cancer, heart attack), (4) parental psychiatric disorder, and
      (5) physical or sexual abuse by a family member-were an important factor in
      change. Forty-four percent (8 of 18) of the infants whose mothers reported
      negative life events changed attachment classifications from infancy to early
      adulthood. Only 22% (7 of 32) of the infants whose mothers reported no such
      events changed classification, p < .05. These results support Bowlby's hypothesis
      that individual differences in attachment security can be stable across
      significant portions of the lifespan and yet remain open to revision in light of
      experience. The task now is to use a variety of research designs, measurement
      strategies, and study intervals to clarify the mechanisms underlying stability
      and change.

PMID- 10953935
TI  - Continuity and discontinuity of attachment from infancy through adolescence.
AB  - This study reports relations between infant Ainsworth Strange Situation
      classifications, negative life events, and Adolescent Attachment Interview
      classifications. Overall, the stability of secure versus insecure classifications
      was 77%, and infant attachment classification was a significant predictor of
      adolescent attachment classification. Chi-square analyses indicate that negative
      life events are significantly related to change in attachment classification. The
      sample (n = 30) is drawn from the Family Lifestyles Project (FLS), an ongoing
      longitudinal study of children's development within the context of
      nonconventional family lifestyles. The distribution of family lifestyles within
      this study, unlike those in the full FLS sample, represent a higher proportion of
      conventional two-parent families (40%). There were no differences between
      adolescents reared in conventional or nonconventional families in the
      distribution of adolescent attachment security, the experience of negative life
      events, or the continuity of attachment from infancy through adolescence.

PMID- 10953936
TI  - Attachment from infancy to early adulthood in a high-risk sample: continuity,
      discontinuity, and their correlates.
AB  - This study explores the stability of attachment security and representations from
      infancy to early adulthood in a sample chosen originally for poverty and high
      risk for poor developmental outcomes. Participants for this study were 57 young
      adults who are part of an ongoing prospective study of development and adaptation
      in a high-risk sample. Attachment was assessed during infancy by using the
      Ainsworth Strange Situation (Ainsworth & Wittig) and at age 19 by using the
      Berkeley Adult Attachment Interview (George, Kaplan, & Main). Possible correlates
      of continuity and discontinuity in attachment were drawn from assessments of the
      participants and their mothers over the course of the study. Results provided no
      evidence for significant continuity between infant and adult attachment in this
      sample, with many participants transitioning to insecurity. The evidence,
      however, indicated that there might be lawful discontinuity. Analyses of
      correlates of continuity and discontinuity in attachment classification from
      infancy to adulthood indicated that the continuous and discontinuous groups were
      differentiated on the basis of child maltreatment, maternal depression, and
      family functioning in early adolescence. These results provide evidence that
      although attachment has been found to be stable over time in other samples,
      attachment representations are vulnerable to difficult and chaotic life
      experiences.

PMID- 10953937
TI  - The stability of attachment security from infancy to adolescence and early
      adulthood: general discussion.
AB  - For over three decades, critics of the developmental and psychometric paradigms
      have argued that individual differences are neither stable, coherent, nor
      clinically significant. The present studies extend a long line of research
      demonstrating the coherence of individual development in attachment security.
      They make it clear that attachment security can be stable from infancy through
      early adulthood and that change in attachment security is meaningfully related to
      changes in the family environment. The task now is to better understand the roles
      of cross-age consistency in caregiver behavior and the structure of mental
      representations of early experience in stability and change.

PMID- 10953938
TI  - Attachment over time.
AB  - Continuity in attachment classification from infancy to late adolescence was
      examined and related to autobiographical memories of childhood, divorce, and
      maladjustment. Eighty-four White middle-class children (48 girls) were seen in a
      modified Strange Situation at 12 months and given the Adult Attachment Interview
      at 18 years. In addition, data were collected on 13-year-olds' childhood
      recollections as well as adolescent, mother, and teacher ratings of maladjustment
      at 13 and 18 years of age. Divorce status of parents also was obtained. Results
      indicated no continuity in attachment classification from 1 to 18 years of age
      and no relation between infant attachment status and adolescent maladjustment.
      Divorce was related to 13-year-olds' childhood recollections as well as to
      insecure attachment status at 18 years. Eighteen-year-olds with insecure
      attachment classification were more likely to rate themselves as maladjusted. The
      results support the idea of attachment as an evolving representation dependent
      upon the nature of the family environment as indexed by divorce.

PMID- 10953939
TI  - Depressive symptoms and co-occurring depressive symptoms, substance abuse, and
      conduct problems among runaway and homeless adolescents.
AB  - This study examines factors that contribute to depressive symptoms and to co
      occurring depression, substance abuse, and conduct problems among 602 runaway and
      homeless adolescents. The respondents were interviewed in shelters, drop-in
      centers, and directly on the streets in four Midwestern states (Missouri, Iowa,
      Nebraska, and Kansas). Results indicate that although family-of-origin factors
      contribute to depressive symptoms and comorbidity among runaway and homeless
      adolescents, experiences and behaviors when the adolescents are on their own also
      have powerful effects. The authors discuss the findings from a life-course
      perspective focusing on mechanisms through which street experiences accentuate or
      amplify already high levels of psychological distress and behavioral problems
      among this population of young people.

PMID- 10953940
TI  - Behavior problems among children from different family structures: the influence
      of genetic self-selection.
AB  - To examine both genetic and environmental influences on children's behavior
      problems in households defined by marital status and sibling relatedness, this
      study applied behavioral genetic methodology to four groups totalling 1524
      sibling pairs drawn from 796 households: (1) two-parent full siblings, (2) two
      parent half siblings, (3) mother-only full siblings, and (4) mother-only half
      siblings. Model-fitting procedures found that within-group variation on four
      subscales from the Behavior Problems Index was best explained by a model
      including both genetic and shared environmental factors. This model was then fit
      to the behavior problems means of the four groups. Its successful fit to these
      mean structures suggested that mean-level differences between groups were
      explained with the same influences that accounted for within-group variation.
      Genetic influences accounted for 81% to 94% of the mean-level difference in
      behavior problems between the two-parent, full sibling and the mother-only, half
      sibling groups. In contrast, shared environmental influences accounted for 67% to
      88% of the mean-level difference in behavior problems between the two-parent,
      full sibling and mother-only, full sibling groups. The genetic influences are
      interpreted in terms of genetic self-selection into family structures.

PMID- 10953941
TI  - Parenting among low-income, African American single mothers with preschool-age
      children: patterns, predictors, and developmental correlates.
AB  - Dimensions and patterns of parenting were examined in a sample of 193 low-income
      African American single mothers with preschool-age children. Factor analyses
      yielded three dimensions: Aggravation, Nurturance, and Cognitive Stimulation.
      Cluster analysis yielded four patterns of parenting: Aggravated but Nurturant;
      Cognitively Stimulating; Patient and Nurturant; and Low Nurturance. Discriminant
      function analysis was used to predict membership in each of the four parenting
      clusters. Two composite functions emerged, the first representing maternal well
      being (locus of control, depressive symptoms), the second representing
      sociodemographic characteristics (maternal education, duration on welfare, age at
      first birth), accounting for 93% of between-groups variability. Children's scores
      on measures of cognitive school readiness and personal maturity were
      significantly related to parenting pattern, even after controlling for
      significant predictors of parenting pattern; children's verbal ability was no
      longer related to parenting pattern once significant maternal characteristics
      were controlled. Findings are discussed in terms of contributions to the
      literature on parenting and in terms of implications for welfare policy and
      programs.

PMID- 10953942
TI  - Effects of conflict resolution training integrated into a kindergarten
      curriculum.
AB  - The effectiveness of a conflict resolution training program was examined in an
      American midwestern suburban elementary school. Participants were 80
      kindergartners randomly assigned to an experimental or control condition in
      morning or afternoon time blocks. Children in the experimental condition received
      9 hr of conflict resolution training integrated into a curriculum unit on
      friendship taught daily for 4 consecutive weeks. Children in the control
      condition were taught the identical friendship unit for the same period of time
      without conflict resolution training. Teachers rotated equally across conditions.
      Significant differences between trained and untrained children occurred in their
      knowledge and retention of the conflict resolution procedure, willingness and
      ability to use the procedure in conflict situations, and conceptual understanding
      of friendship.

PMID- 10953943
TI  - The nature and correlates of underachievement among elementary schoolchildren in
      Hong Kong.
AB  - This study investigated for the first time several characteristics of
      underachievement in a large sample of Hong Kong elementary schoolchildren. More
      males were identified as underachievers than females, but the ratio was
      substantially less than the two-to-one rate typically found in the American
      literature. The stability and persistence of underachievement increased during
      the elementary school years, and the stability of underachievement tended to be
      higher in subject matter that was relatively more difficult, which varied with
      gender. Underachievement became more specific to particular academic subjects
      rather than more general across the elementary grades. Parents and teachers, but
      not the children themselves, perceived that underachievers were more capable than
      same-grade nonunderachievers (who score lower on ability tests), although this
      awareness is more likely directed at male than female underachievers, which has
      been observed in other samples. In grades 1-4, teachers provided extra mentoring,
      communications, and support to underachievers. Thereafter, underachievers became
      more disruptive, impatient, and aggressive in school and perhaps at home. At that
      point, teachers became less supportive, offered less extra mentoring, and applied
      greater behavioral control over underachievers. Underachieving children also
      perceived that their parents became less supportive and used more discipline in
      grades 5-6 relative to grades 3-4. These correlates of underachievement suggests
      the existence of a syndrome of underachievement that separates underachievers
      from children who have the same grades but lower mental ability.

PMID- 10953944
TI  - Patterns of service use in preschool children: correlates, consequences, and the
      role of early intervention.
AB  - This article explores service use broadly by examining the mix of educational,
      health, and psychosocial services that preschool children received in the fifth
      year of life. The sample included 869 children who participated in the Infant
      Health and Development Program, an early intervention program designed to
      evaluate the efficacy of a comprehensive early intervention for low-birth-weight,
      premature infants during the first 3 years of life and who were followed until
      age 5. Cluster analyses of services at age 5 yielded 4 service groups--basic
      health only (doctor visits; n = 114); basic health and educational services
      (doctor visits and school/preschool; n = 444); basic health, educational, and
      psychosocial services (or multiple services; doctor visits, school/preschool, and
      psychosocial services; n = 129); and specialized health and educational services
      (doctor visits, school/preschool, emergency room visits and special medical
      visits [ear and/or eye examinations]; n = 182). Results suggest that neonatal
      health conditions, maternal education at the time of the child's birth, child
      developmental status at age 3, and maternal health, family income, and insurance
      status at age 5 were associated with patterns of services at age 5. Patterns of
      use are consistent over time (the first 3 years of life to the 5th year of life).
      After covarying the correlates of the service patterns, participation in the
      early intervention was not associated with patterns of services at age 5, and
      service patterns were associated with child well-being (health, school readiness,
      mental health), but results differed by intervention status. Findings are
      discussed in terms of preventive, responsive, and deficit models of service use.

PMID- 10953945
TI  - Introduction: Hemochromatosis population screening.

PMID- 10953946
TI  - Genetic hemochromatosis: detection, management, and population screening.
AB  - Genetic hemochromatosis (GH) is an inherited disease that results in iron
      overload, and, if untreated, causes irreversible organ damage. Knowledge and
      understanding of the early features of the condition, often nonspecific, and of
      the diagnostic route are necessary to detect iron overload and diagnose GH before
      irremedial damage has been done. Genetic testing now plays an important role in
      diagnosis. Management of the patient with established GH centers on venesection
      to return body iron levels to normal, treatment of the complications of GH, and
      family screening for GH. Population screening for GH, the ideal strategy to
      prevent any morbidity from iron overload, has not yet been accepted by public
      health professionals, largely because of the lack of data on the disease
      penetrance in genetically susceptible individuals.

PMID- 10953947
TI  - Screening for hemochromatosis in routine medical care: an evaluation of mean
      corpuscular volume and mean corpuscular hemoglobin.
AB  - Our aim was to evaluate the potential utility of mean corpuscular volume (MCV)
      and mean corpuscular hemoglobin (MCH) to detect hemochromatosis. We computed the
      accuracy of MCV and MCH cut-off points > or = upper reference limits using data
      from 94 probands and 132 white controls. Our reference ranges are MCV 80.0-97.0
      fL and MCH 26.0-32.0 pg. Sensitivity of MCV was 8.6-48.3% for men and 2.8-44.4%
      for women (cut-off points > or = 105.0 - > or = 97.0 fL, respectively).
      Sensitivity of MCH was 33.9-70.7% for men and 19.6-50.0% for women (cut-off
      points > or = 34.0 - > or = 32.0 pg, respectively). Using MCV and a
      hemochromatosis frequency typical of many western Caucasian populations (0.005),
      positive predictive values (PV+) were 2.1-100.0% in men and 4.2-100.0% in women.
      Using MCH, PV+ were 1.7-8.2% in men and 1.8-6.8% in women. We also calculated PV+
      using the hemochromatosis frequency 0.015, which could occur in persons receiving
      medical care. Using MCV cut-off points > or = 101.0 fL, PV+ were 8.9-100.0% in
      men and 100.0% in women with maximum sensitivities of 24.1% and 25.0%,
      respectively. Using MCH testing, PV+ was 21.5% in men (cut-off point > or = 34.0
      pg) and 18.2% in women (cut-off point > or = 33.0 pg) with sensitivities of 33.9%
      and 37.0%, respectively. Using MCV or MCH, sensitivity and PV+ for the HFE
      genotype C282Y/C282Y were generally greater than for "nonclassical" HFE
      genotypes. All negative predictive values in our study were > or = 98.5%. We
      conclude that supranormal values of MCV or MCH could be used to detect
      hemochromatosis in white persons of western European descent who are receiving
      routine medical care. Comparisons of MCV, MCH, and transferrin saturation testing
      and other implications of MCV and MCH testing for hemochromatosis in medical care
      are discussed.

PMID- 10953948
TI  - Population screening for hemochromatosis by PCR using sequence-specific primers.
AB  - Over 90% of patients with hemochromatosis in the United Kingdom are homozygous
      for the C282Y mutation on the HFE gene. The Centers for Disease Control (CDC) in
      the United States has recommended that adults should be screened for HFE
      mutations to identify susceptible individuals before onset of disease. The aim of
      this study was to evaluate the polymerase chain reaction using sequence-specific
      primers (PCR-SSP) as a method of large-scale population screening for the common
      HFE gene mutations, H63D and C282Y. A total of 10,583 consenting blood donors
      were tested using nonautomated procedures. Three alleles, termed HFE-1, -2, and 
      3, were detected with phenotype frequencies of 94.56%, 28.33%, and 15.79%,
      respectively, and gene frequencies of 0.76421, 0.15342, and 0.08237,
      respectively. All donors identified as homozygous for the C282Y mutation or
      heterozygous for both the H63D and C282Y mutations were confirmed by heterduplex
      analysis and/or PCR-SSP. The number of technical failures that affected the
      identification of donors homozygous for the C282Y mutation was 390 giving an
      overall repeat rate 3.7%, although this fell to 1% over the last quarter of the
      study. This study demonstrates that PCR-SSP may be used for large-scale
      population screening for the C282Y genotype associated with hemochromatosis.

PMID- 10953949
TI  - Detection of C282Y and H63D in the HFE gene.
AB  - The gene for hemochromatosis was identified in 1996 and two mutations were found.
      Homozygosity for one of these, C282Y, is associated with hemochromatosis in a
      high percentage of patients. Genetic analysis of patient DNA is, therefore, a
      very useful tool to aid and confirm diagnosis and to screen asymptomatic
      relatives of patients to identify those at risk of developing this common, easily
      treated disease.

PMID- 10953950
TI  - A reverse-hybridization assay for the rapid and simultaneous detection of nine
      HFE gene mutations.
AB  - Hereditary hemochromatosis (HH) is a very common autosomal recessive disorder of
      iron metabolism and frequently associated with mutations in the HFE gene.
      Molecular genetic testing for HFE mutations is considered valuable for carrier
      identification, as well as for early diagnosis of the disease, allowing simple
      treatment by phlebotomy and normal survival of patients. We have developed a
      reverse-hybridization assay for the routine diagnosis of eight previously
      described and one novel (E168Q) HFE point mutations. The test is based on
      multiplex DNA amplification and ready-to-use membrane teststrips, which contain
      oligonucleotide probes for each wild-type and mutated allele immobilized as an
      array of parallel lines. The procedure is rapid and accessible to automation on
      commercially available equipment, and by adding new probes the teststrip can
      easily be adapted to cover an increasing number of mutations.

PMID- 10953951
TI  - Novel method for molecular detection of the two common hereditary hemochromatosis
      mutations.
AB  - We describe a novel molecular screening technique for hereditary hemochromatosis
      through which HFE genotypes at codon positions 282 and 63 are simultaneously
      detected. The technique combines multiplex PCR and denaturing high-performance
      liquid chromatography (DHPLC) and allows automated high-throughput analysis. We
      used this method to genotype 43 previously characterized anonymous DNA specimens
      in blinded fashion and found multiplex PCR/DHPLC 100% accurate when compared with
      PCR/restriction enzyme digestion, yet far more efficient.

PMID- 10953952
TI  - Large-scale screening for HFE mutations: methodology and cost.
AB  - Large-scale detection of mutations at the DNA level requires the development of
      cost-effective methods for the screening of thousands of samples. Hemochromatosis
      is an appropriate testing ground for the development of such technologies, and we
      report the methods that we have developed to screen large numbers of samples
      using equipment available in most laboratories. We are able to examine DNA
      samples for two mutations in the HFE gene at a cost of only slightly over $8 per
      sample, a cost that includes overhead and the approximately 40 hr per week of
      technician time required to perform the studies. The technologies involved in
      mutation analysis are evolving rapidly and ultimately more highly automated,
      lower-cost technologies may become available. At present, however, we find the
      methodology described to be very suitable for large-scale, low-cost mutation
      screening.

PMID- 10953953
TI  - Pitfalls in the genetic diagnosis of hereditary hemochromatosis.
AB  - The widespread use of the genotype assay that identifies the common C282Y
      mutation in the HFE gene has allowed an earlier diagnosis to be made in many
      subjects. A significant number of these patients may have no evidence of
      phenotypic disease and have a normal serum ferritin level. This phenomenon is
      more common when the genotype assay is used to screen populations rather than
      higher-risk groups such as family members of a proband with hereditary
      hemochromatosis. Moreover, patients with significant iron overload may be wild
      type for the C282Y mutation and have no other demonstrable mutation of the HFE
      gene. The HFE genotype assay has recently been found to give a false-positive
      C282Y homozygous result in half of the subjects in one population screening study
      due to the presence of a single nucleotide polymorphism (SNP) that interfered
      with primer binding in the PCR assay. The problem may be overcome by using
      alternate primers. A number of other groups have confirmed the finding but in a
      much smaller number of subjects, whereas others found that their assays were not
      affected by the SNP. The use of the HFE genotype assay as the sole diagnostic
      criterion for hereditary hemochromatosis is not recommended. The genotype assay
      should be used as an adjunct to the established methods of demonstrating iron
      overload and be viewed as a predictor of either the presence of iron overload or
      the subsequent development of iron overload during an individual's lifetime.

PMID- 10953954
TI  - 5569G/A polymorphism of the HFE gene: no implications for C282Y genotyping in a
      hemochromatosis screening study of 65,238 individuals.
AB  - In a previous hemochromatosis screening study including a total of 65,238
      individuals, 566 persons were genotyped for the C282Y and the H63D mutations. Of
      these, a total of 433 samples (298 homozygous C282Y and 135 homozygous wild type)
      were reanalyzed to investigate if the potential presence of the newly described
      5569G/A polymorphism had confounded the genotyping results for the C282Y
      mutation. Genotyping with a polymorphism-insensitive primer pair yielded no
      samples that altered their genotype. By utilizing the polymorphism-sensitive
      primer pair and elevated annealing temperatures, 133 samples previously genotyped
      as heterozygous C282Y were reanalyzed to verify the presence of the polymorphism
      in the population studied. Out of a total of 266 chromosomes, we found the
      polymorphism present in 9 chromosomes, yielding an allele frequency of 0.034 in
      this particular subpopulation. In one of the samples, the polymorphism was
      present on the same DNA strand as the C282Y mutation. We conclude that in the
      population studied, the 5569 G/A polymorphism is present, but its presence had no
      implications for the outcome of the previous genotyping. Nevertheless, we
      recommend that C282Y genotyping by restriction endonuclease digestion of PCR
      products in the future should utilize a primer pair that is not influenced by the
      5569G/A polymorphism.

PMID- 10953955
TI  - Uncommon mutations and polymorphisms in the hemochromatosis gene.
AB  - Hereditary hemochromatosis (HH) is a common autosomal recessive disorder of iron
      metabolism. Iron absorption from the gut is inappropriately high, resulting in
      increasing iron overload. The hemochromatosis gene (HFE) was identified in 1996
      by extensive positional cloning by many groups over a period of about 20 years.
      Two missense mutations were identified. Homozygosity for one of these, a
      substitution of a tyrosine for a conserved cysteine (C282Y), has now clearly been
      shown to be associated with HH in 60-100% of patients. The role of the second
      mutation, the substitution of an aspartic acid for a histidine (H63D), is not so
      clear but compound heterozygotes for both these mutations have a significant risk
      of developing HH. Here we review other putative mutations in the HFE gene and
      document a number of diallelic polymorphisms in HFE introns.

PMID- 10953956
TI  - Celtic origin of the C282Y mutation of hemochromatosis.
AB  - The main hereditary hemochromatosis mutation C282Y in the HFE gene was recently
      described, and the C282Y frequencies were reported for various European
      populations. The aim of this synthesis is to compile the Y allele frequencies of
      the C282Y mutation for 40 European populations. The most elevated values are
      observed in residual Celtic populations in Ireland, the United Kingdom, and
      France, in accordance with the hypothesis of Simon et al. (1980) concerning a
      Celtic origin of the hereditary hemochromatosis mutation.

PMID- 10953957
TI  - Hereditary hemochromatosis in Spain.
AB  - The C282Y mutation of the HFE gene has been reported as the main cause of
      hereditary hemochromatosis (HH). Another missense mutation (H63D) has also been
      detected at an increased frequency in a compound heterozygote state with the
      C282Y mutation in HH patients. However, these two mutations are not present in
      all of the HH patients, indicating that other mutations in the HFE gene, or in
      other loci, should exist. The present study reports the frequencies of the C282Y
      and H63D mutations in 74 Spanish HH patients and the results of the sequencing
      analysis of the HFE exons, intron-exon boundaries, and 588 bp of the 5' region in
      5 patients negative for the C282Y mutation. We have detected a high frequency of
      the C282Y mutation (85.1%) in Spanish HH patients, indicating that this mutation
      is the most common defect associated with the disease in Spain. The screening of
      the HFE regions in our patients without the C282Y mutation has revealed the
      presence of five polymorphisms. However, no other pathological mutations have
      been found. Therefore, further efforts to characterize the unscreened part of the
      HFE gene or other loci should be taken to identify the potential genetic factors
      causing HH in the C282Y-negative patients.

PMID- 10953959
TI  - Geography of HFE C282Y and H63D mutations.
AB  - Hereditary hemochromatosis (HH) is a common autosomal recessive disorder causing
      inappropriate dietary iron absorption that affects North Europeans. HH is
      associated with the C282Y mutation of the HFE gene, and the H63D mutation to a
      lesser degree. Both mutations are abundant in Europe, with H63D also appearing in
      North Africa, the Middle East, and Asia. Emigration from Europe over the past 500
      years has introduced C282Y and H63D to America, Australia, New Zealand, and South
      Africa in an essentially predictable fashion. The distinctive characteristics of
      the population genetics of HH are the confined racial distribution and high
      frequency in North European peoples. C282Y frequencies in North Europeans are
      typically between 5% and 10%, with homozygotes accounting for between 1/100 and
      1/400 of these populations. The scarcity of the C282Y mutation in other
      populations accounts for the lack of HH in non-Europeans.

PMID- 10953958
TI  - A pilot C282Y hemochromatosis screening in Italian newborns by TaqMan technology.
AB  - Hereditary hemochromatosis (HH) is a disorder of iron metabolism that leads to
      iron overload in middle age and can be caused by homozygosity for the C282Y
      mutation in the HFE gene. Preliminary studies have estimated the frequency of
      this mutation at 0.5-1% in Italy, but this has not been verified on a large
      sample. We analyzed 1,331 Italian newborns for the C282Y mutation in the HFE gene
      using dried blood spots (DBS) from the Neonatal Screening Center in Turin, Italy.
      The mutation was assessed using a semi-automatable 5'-nuclease assay (TaqMan
      technology). We detected 55 heterozygotes and no homozygotes in our sampling,
      resulting in an overall frequency of 2.1% +/- 0.6 for the C282Y allele.
      Differences in allele frequency were observed, and ranged from 2.7% +/- 1.3 in
      samples from Northern Italy, to 1.7% +/- 0.9 in samples from Central-Southern
      Italy. The low frequency of the at-risk genotype for iron overload suggests that
      genetic screening for HFE in Italy would not be cost effective. The present
      study, in addition to defining C282Y frequency, documents detection of the major
      HFE mutation on routine DBS samples from neonatal screening programs using a semi
      automatable, rapid, reliable, and relatively inexpensive approach.

PMID- 10953960
TI  - Transferrin saturation phenotype and HFE genotype screening for hemochromatosis
      and primary iron overload: predictions from a model based on national, racial,
      and ethnic group composition in central Alabama.
AB  - There is interest in general population screening for hemochromatosis and other
      primary iron overload disorders, although not all persons are at equal risk. We
      developed a model to estimate the numbers of persons in national, racial, or
      ethnic population subgroups in Jefferson County, Alabama, who would be detected
      using transferrin saturation (phenotype) or HFE mutation analysis (genotype)
      screening. Approximately 62% are Caucasians, 37% are African Americans, and the
      remainder are Hispanics, Asians, or Native Americans. The predicted phenotype
      frequencies are greatest in a Caucasian subgroup, ethnicity unspecified, which
      consists predominantly of persons of Scotch and Irish descent (0.0065 men, 0.0046
      women), and in African Americans (0.0089 men, 0.0085 women). Frequencies of the
      HFE genotype C282Y/C282Y > or = 0.0001 are predicted to occur only among
      Caucasians; the greatest frequency (0.0080) was predicted to occur in the
      ethnicity-unspecified Caucasian population. C282Y/C282Y frequency estimates were
      lower in Italian, Greek, and Jewish subgroups. There is excellent agreement in
      the numbers of the ethnicity-unspecified Caucasians who would be detected using
      phenotype and genotype criteria. Our model also indicates that phenotyping would
      identify more persons with primary iron overload than would genotyping in our
      Italian Caucasian, Hispanic, and African American subgroups. This is consistent
      with previous observations that indicate that primary iron overload disorders in
      persons of southern Italian descent and African Americans are largely
      attributable to non-HFE alleles. Because the proportions of population subgroups
      and their genetic constitution may differ significantly in other geographic
      regions, we suggest that models similar to the present one be constructed to
      predict optimal screening strategies for primary iron overload disorders.

PMID- 10953961
TI  - Technical, genetic, and ethical issues in screening and testing of African
      Americans for hemochromatosis.
AB  - To define more precisely populations in which hemochromatosis is frequent to
      rare, problems of racial classification are introduced, with particular reference
      to Europeans and African-Americans. Because the category "Caucasian" includes a
      multitude of dissimilar peoples, the categories Europeans and European-Americans
      have been substituted for Caucasian, which is archaic. The background of
      discrimination in sickle hemoglobin programs for African-Americans are then
      analyzed, including, discrimination by employers, life insurance, and selective
      mandatory testing. Discrimination and selective testing of African-American
      employees of the Lawrence Livermore Laboratory continues today without prior
      consent, as it has since the 1970s. Dissimilarities between the genetics of
      hemochromatosis in Europeans and their descendants, Africans, and African
      Americans are briefly analyzed. Finally, it is concluded that because
      hemochromatosis is unlike sickle hemoglobin in that it is potentially preventable
      and treatable, prevention and treatment principles should apply as in other
      diseases. Furthermore, because hemochromatosis is so common in European
      Americans, discrimination, if practiced, would not be selective for African
      Americans.

PMID- 10953962
TI  - Genetic discrimination and screening for hemochromatosis: then and now.
AB  - Any two people on earth, save for identical twins, share in common roughly 99.9%
      of their genetic make-up. That 0.1% difference represents not just what, on a
      molecular level, distinguishes us from one another, but also has reportedly
      served as a basis for excluding individuals from insurance, employment, adoption,
      educational opportunities, family relations, as well as perceived life options.
      The first federal study of genetic discrimination, discrimination based on
      genotype as opposed to phenotype, included treated hereditary hemochromatosis
      (HH) as one of only five genotypes possibly providing a basis for discrimination.
      HH was selected because if a successfully treated condition that is nonetheless
      genetic but which, if properly managed, leaves affected individuals at no greater
      morbidity or mortality risk than the general population, then genotype
      independent of phenotype apparently provided a basis for exclusions. Since the
      publication of those results, much more is known about the genotypic and
      phenotypic variation of affected individuals. This paper discusses what is
      presently known about HH and genetic discrimination.

PMID- 10953963
TI  - Early detection of genetic hemochromatosis: should all young adults be offered
      the genetic test?
AB  - Genetic hemochromatosis (GH) is a late-onset, autosomal recessive disorder. The
      majority of those at risk from iron overload and its clinical consequences may be
      detected by a simple genetic test. Furthermore, treatment by phlebotomy, if
      instituted early, removes excess iron and prevents the complications of iron
      overload which include arthralgia, diabetes, and cirrhosis of the liver. GH seems
      to be an obvious candidate for inclusion in national screening programs. However,
      important questions remain concerning the proportion of individuals with the high
      risk genotype who eventually show clinical manifestations of iron overload and
      the significance of heterozygosity for haemochromatosis in terms of morbidity.
      Until these questions are resolved, the introduction of widespread genetic
      screening cannot be justified.

PMID- 10953964
TI  - Postscript: a status report on hemochromatosis population screening.

PMID- 10953965
TI  - Effects of growth hormone and prolactin on hematopoiesis.
AB  - The use of the neuroendocrine hormones growth hormone (GH) and prolactin (PRL) in
      preclinical models, demonstrating promotion of hematopoietic recovery and immune
      function, offers promise for several clinical situations. These hormones do not
      appear to produce the same extent of immune/hematopoietic effects when compared
      to conventional hematopoietic and immune stimulating cytokines (i.e. G-CSF or
      interleukin-2). However, their pleiotropic effects and limited toxicity after
      systemic administration makes them attractive to test in myeloablative
      situations. More work needs to be performed to understand the mechanism(s) of GH
      and PRL action, particularly with regard to hematopoietic progenitor cell
      expansion and differentiation both in normal and pathologic situations.

PMID- 10953966
TI  - Genetic susceptibility to childhood acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The
      origin of this disease can be explained by a combination of genetic
      susceptibility factors and environmental exposures. For the purpose of our study
      it can be considered as a complex disease, caused by the "carcinogenic" effect of
      the environment modified by a series of genes. In population, these genes tend to
      occur in allelic forms representing functional polymorphisms thus explaining
      inter-individual variability in cancer susceptibility. The latter can be
      evaluated more realistically in childhood ALL than in sporadic cancers of the
      adult because of its relatively short latency period. We asked therefore, the
      question about the role of genes controlling the efficiency of xenobiotics
      metabolism in childhood leukemogenesis. Xenobiotics (drugs and carcinogens) are
      excreted from the body after metabolic conversion by enzymes mediating oxidation
      activation (Phase I) and conjugation detoxificaton (Phase II). Functional
      variants of these enzymes, resulting from known DNA polymorphisms in the
      corresponding genes, were shown to influence the risk to a variety of solid
      tumours in adults. A case-control study on ALL patients and healthy controls in a
      French-Canadian population was carried out by examining the loci of Phase I,
      CYP1A1 and CYP2D6, as well as Phase II enzymes, GSTM1, GSTT1, NAT1 and NAT2. The
      NAT2 slow-acetylator, CYP1A1*2A and GSTM1 null genotypes were shown to be
      significant risk determinants of ALL (OR=1.6, 1.8 and 1.8, respectively),
      whereas, polymorphisms in CYP2D6 and GSTT1 genes did not seem to play an
      important role in the aetiology of ALL. Interestingly, the risk associated with
      NAT2 slow-acetylators was most apparent among males homozygous for NAT1*4
      (OR=3.3) whereas girls carrying the CYP1A1*4 allele were significantly
      underrepresented in the patient group (OR=0.2). These findings point to a gender
      specific effect of DNA variants which, at least in part, may explain why ALL is
      more prevalent among boys. To assess gene-gene interactions, NAT2 slow
      acetylators were considered together with GSTM1 null genotypes and CYP1A1*2A
      alleles. The combined presence of two risk-elevating genotypes appeared to confer
      an increased risk of ALL among the carriers (OR=2.6). This risk was increased
      further (OR=3.3) when all three genotypes occurred in the same individuals
      indicating that the combination of susceptibility variants is more predictive of
      risk then either of them independently. The association of leukemogenesis in
      children with metabolising gene variants suggests causal relation to
      environmental exposures.

PMID- 10953967
TI  - CD44v10 in hematopoiesis and stem cell mobilization.
AB  - Transplantation of hematopoietic progenitor cells provides in many instances of
      malignant tumors an ultimate chance of curative therapy, whereby the transfer of
      peripheral blood stem cells (PBSC) may even be advantageous as compared to bone
      marrow cells. Yet, the transfer of PBSC requires mobilization of stem cells into
      the periphery, which is mostly achieved via hematopoietic growth factors like G
      CSF. Although G-CSF has been found to efficiently mobilize stem cells in most
      instances, some patients do not or insufficiently respond to G-CSF treatment In
      addition, G-CSF treatment may by accompanied by maturation of the most primitive
      progenitors and this may have an impact on stem cell homing and recovery of
      hemopoiesis. Therefore, additional approaches for stem cell mobilization have
      been searched for, in particular mobilization via a blockade of an adhesion
      molecule expressed by CD34-positive cells, like VLA-4 (CD49d) and the
      hematopoietic isoform of CD44 (CD44s). We recently described that in the mouse
      one of the CD44 variant isoforms, CD44v10, is expressed on a subpopulation of
      bone marrow cells, whereas a CD44v10 receptor-globulin only binds to stromal
      elements. These features appeared promising for anti-CD44v10 as a means of stem
      cell mobilization. Indeed, treatment with anti-CD44v10 revealed promising results
      concerning the recovery of multilineage colony forming units in the spleen and
      the peripheral blood. We here summarize features of expression and function of
      CD44 in hematopoiesis an provide further evidence for anti-CD44v10 as a means to
      mobilize hematopoietic progenitor cells.

PMID- 10953968
TI  - The role of cytokines in the pathogenesis and management of AIDS-related
      lymphomas.
AB  - AIDS-related non-Hodgkin lymphomas (AIDS-NHL) consistently derive from B-cells
      and are characterized by extreme clinical aggressiveness. At histological level,
      AIDS-NHL are classified as AIDS-related Burkitt's lymphoma (AIDS-BL), AIDS
      related diffuse large cell lymphoma (AIDS-DLCL) and AIDS-related primary effusion
      lymphoma (AIDS-PEL). The role of cytokines in the pathogenesis and management of
      AIDS-NHL has been studied to a certain extent. Production of large quantities of
      human IL-10 occurs frequently in AIDS-BL and correlates with latent EBV infection
      of the tumor clone. Lesser amounts of the cytokine are released in EBV negative
      cases. The pathogenetic role of IL-10 in AIDS-BL is suggested by the observation
      that IL-10 antisense oligonucleotides inhibit proliferation of the lymphoma. A
      significant fraction of AIDS-BL cell lines produce TNFbeta. Among AIDS-NHL, the
      release of TNFbeta appears to be specific for AIDS-BL. The pathogenetic relevance
      of TNFbeta in lymphomagenesis is suggested by the observation that some BL cell
      lines use TNFbeta as an autocrine growth factor. Some cases of AIDS-BL,
      particularly those carrying EBV infection, also secrete IL-6, IL-7 and IL-12.
      With respect to AIDS-DLCL, many cases express the IL-6R, rendering these cells
      responsive to the paracrine stimulation by the IL-6 produced by nearby T-cells,
      macrophages and endothelial cells which are frequently abundant in these tumor
      samples. The tumor clone itself, however, generally fails to release IL-6. AIDS
      PEL is characterized by secretion of large amounts of IL-6 and IL-10. Some PEL
      cases also release oncostatin M. Apart from human IL-6, PEL also express viral IL
      6, which is encoded by the HHV-8 genome. The biological relevance of both IL-6
      and IL-10 in PEL proliferation and growth has been recently clarified in vitro
      and in vivo. Overall, these data suggest that activation of different cytokine
      loops clusters with different clinico-pathologic categories of AIDS-NHL and may
      represent the potential target of novel therapeutic strategies.

PMID- 10953969
TI  - Cellular and molecular aspects of human CD34+ CD38- precursors: analysis of a
      primitive hematopoietic population.
AB  - Hematopoiesis is a complex, highly regulated process in which a small number of
      primitive stem cells produce all the mature blood and immune cells required by an
      animal throughout its life. In this review, we summarize current understanding of
      human CD34+ CD38- cells, a small subclass of hematopoietic cells, which is
      enriched for primitive precursors, including stem cells. This review emphasizes
      functional, molecular and immunophenotypic characteristics of the cells and
      includes some of the factors which are believed to regulate the survival, growth
      and differentiation of this important class of cells.

PMID- 10953970
TI  - Ubiquitin-proteasome system and increased sensitivity of B-CLL lymphocytes to
      apoptotic death activation.
AB  - The ubiquitin-proteasome-dependent proteolytic system has been reported to
      regulate apoptotic cell death in many experimental cell models. We recently found
      that B-CLL (chronic lymphocytic leukemia) lymphocytes are hypersensitive to
      apoptotic death activation through specific inhibition of proteasome function by
      lactacystin. Lactacystin efficiently activates apoptotic death process in B-CLL
      lymphocytes at doses at which no apoptotic effect can be observed in normal human
      lymphocytes in which 10-fold higher doses of lactacystin are required to weakly
      induce apoptosis. This hypersensitivity of B-cell CLL may be a result of an
      altered ubiquitin pathway and proteasomal proteolysis in these malignant cells,
      and this alteration could be specific for this malignancy. Together with other
      published works, these results suggest that lactacystin, though not per se a
      discriminatory inhibitor of the ubiquitinated protein processing/degradation, can
      nonetheless be discriminatory in the apoptotic cell response between B-CLL and
      normal lymphocytes: the property that promises efficacy in clinical trials of B
      cell CLL. This hypothesis is documented by the fact that lymphocytes from
      patients in complete remission become resistant to lactacystin-induced apoptosis
      as normal lymphocytes do.

PMID- 10953971
TI  - Internal deletions within the BCL6 gene in B-cell non-Hodgkin's lymphoma.
AB  - The BCL6 gene, encoding a POZ/Zinc finger protein which acts as a transcriptional
      repressor, is frequently altered at its 5' non-coding region by 3q27 chromosomal
      translocations in B-cell non-Hodgkin's lymphoma (NHL). BCL6 rearrangement is one
      of the most common genetic abnormalities in NHL. As a result of translocations,
      the regulatory region of the BCL6 gene is replaced by an heterologous reciprocal
      partner such as the immunoglobulin (IG) genes. Promotor substitution leads to
      deregulation of the BCL6 expression, which may be associated with
      lymphomagenesis. Recent studies have shown that the 5' non-coding region of the
      BCL6 gene is also subject to somatic hypermutation physiologically operating in
      germinal center (GC) B-cells in a similar pattern to that of the IG genes. There
      is little evidence to show that structural alterations of the BCL6 gene may be
      caused by mechanisms other than chromosomal translocations. To date, five cases
      with NHL exhibiting gross BCL6 deletions of the 1.5-2.4 kb have been reported.
      These deletions occurred in the same region as translocational breakpoints and
      the somatic hypermutations cluster, but independently of chromosomal
      rearrangements. The deletions overlapped at the 270 bp region and this region
      contains a putative protein-binding sequence which may play a role in the
      regulation of the BCL6 expression. Small separated deletions of 22-101 bp, which
      may also contain protein-binding sequences, were evident in another NHL case. In
      contrast to the TAL1 deletion in T-cell acute lymphoblastic leukemia (ALL), the
      BCL6 deletion is considered to be mediated by a mechanism other than aberrant
      activity of the IG recombinase. Internal deletion within the BCL6 gene is a
      recurrent molecular abnormality in B-cell NHL, which is sometimes
      indistinguishable from rearrangements by chromosomal translocations. At present,
      the mechanism of DNA recombination and its role in lymphomagenesis remain
      unknown.

PMID- 10953972
TI  - Management of renal complications in patients with advanced multiple myeloma.
AB  - Although the kidney is frequently involved in malignant monoclonal gammopathy,
      the clinical outcome of the patients varies considerably. We retrospectively
      assessed the clinical course in seventeen patients with acute and chronic renal
      failure suffering from multiple myeloma, and analyzed their case history focusing
      on the therapeutic management, the possible clinical improvement as well as the
      patients' outcome. Treatment included chemotherapy (n = 17), forced diuresis (n =
      3), hemodialysis (n = 11, 7 chronic, 4 intermittent) and plasmapheresis (n = 3).
      Renal function improved in five patients, and was stabilized compensated in four.
      Seven patients developed end-stage renal disease, one refused further treatment
      and was lost for follow up. In addition to renal failure, the most frequent
      complications included local bone destruction (all), anemia (n = 12), low
      platelet count (n = 11), and bacterial infections (n = 9). One year survival rate
      after admission to the nephrology department was 76 percent. Chemotherapy in
      combination with renal replacement therapy may improve the clinical course even
      in MM patients with serum creatinine levels above 3.0 mg/dL or end-stage renal
      disease.

PMID- 10953973
TI  - Randomized comparison of mobilization kinetics of circulating CD34+ cells between
      biweekly CHOP and dose-escalated CHOP with the prophylactic use of lenograstim
      (glycosylated rHuG-CSF) in aggressive non-Hodgkin's lymphoma. The
      lenograstim/Lymphoma Study Group.
AB  - High-dose chemotherapy with autologous hematopoietic stem cell transplantation
      has been expected to result in a promising outcome in high risk aggressive non
      Hodgkin's lymphoma (NHL). However, it remains unknown what type of initial
      chemotherapy is optimal, especially regarding progenitor cell mobilization. Sixty
      three untreated patients with aggressive NHL in a high risk group were randomized
      to either a biweekly arm with 8 cycles of standard CHOP or 6 cycles of the dose
      escalated CHOP arm with cyclophosphamide 1.5 g/m2 and doxorubicin 70 mg/m2.
      Lenograstim (glycosylated rHuG-CSF 2.0 microg/kg/day) was administered daily from
      day 3 to patients in both arms. The mobilization effect of the two regimens on
      circulating CD34+ cells was evaluated. Twenty-seven of 29 patients in the
      biweekly CHOP arm and 33 of 34 patients in the dose-escalated CHOP were
      assessable. Dose-escalated CHOP yielded a significantly higher number of
      circulating CD34+ cells in the first cycle compared with biweekly CHOP (p=0.05).
      The peak number of circulating CD34+ cells with biweekly CHOP did not
      significantly change from cycle to cycle; however, in dose-escalated CHOP, the
      peak number of circulating CD34+ cells mobilized after the fifth and sixth cycle
      was lower than after the first cycle (p=0.07 and 0.009, respectively). Routine
      conventional-dose chemotherapy and low-dose G-CSF can mobilize sufficient CD34+
      cells in patients with aggressive NHL. The mobilization kinetics of circulating
      progenitor cells in patients with aggressive NHL is dependent on the dosage and
      schedule of CHOP.

PMID- 10953974
TI  - Serum levels of soluble interleukin-2 receptor after bone marrow transplantation:
      a true marker of acute graft-versus-host disease.
AB  - To examine whether serum levels of soluble interleukin-2 receptor (sIL-2R) may be
      a good marker of acute graft-versus-host disease (aGVHD), they were determined
      weekly in 56 patients receiving bone marrow transplantation (BMT). Because of
      wide variation in the pre-transplant sIL-2R levels (from 135 to 1918 IU/ml), we
      used a sIL-2R index in this study by comparing the peak levels with the pre
      transplant levels. In agreement with previous reports, there was a significant
      correlation between the grade of aGVHD and the maximal sIL-2R index. The maximal
      sIL-2R index was 4.66 in patients with grade I to IV aGVHD, whereas it was 2.68
      in patients without GVHD. This marker may be useful for monitoring the status of
      aGVHD. However, it was interesting that sIL-2R levels were elevated from the time
      of transplantation until the third week even in patients without GVHD or those
      who received autologous transplantation. Until the third week, no significant
      differences were observed in sIL-2R index between these patients and those who
      developed aGVHD during their clinical courses. After the fourth week, a higher
      sIL-2R index was observed in patients with aGVHD than in the other patients. Some
      factors other than GVHD contribute to the elevation of serum sIL-2R levels, and
      we should recognize the limitations of the measurement of this cytokine.

PMID- 10953975
TI  - Cytoplasmic cytokines in lymphoproliferative disorders: multiple cytokine
      production in angioimmunoblastic lymphadenopathy with dysproteinemia.
AB  - Cytokines play an important role in the pathogenesis of lymphomas via autocrine
      or paracrine mechanisms, or both. Here we determined the proportion of CD3
      positive T lymphocytes containing various types of cytokines in enlarged lymph
      nodes. Lymph nodes were obtained from 16 patients with various
      lymphoproliferative disorders, including 3 cases with angioimmunoblastic
      lymphadenopathy with dysproteinemia (AILD), 3 cases with adult T cell
      leukemia/lymphoma (ATLL), 2 cases with T-cell nonspecific malignant lymphoma (T
      ML), 3 cases with B-cell diffuse large malignant lymphoma (BDL), 3 cases with
      histiocytic necrotizing lymphadenitis (HNL), and 2 cases with non-specific
      lymphadenitis (NSL). The percentages of T lymphocytes positive for cytoplasmic
      cytokines IL-2, IL-4, IL-5, IL-6, IL-13, TNF-alpha, and INF-gamma were
      determined. The percentage of INF-gamma positive T lymphocytes was high in
      reactive lymphadenopathy of NSL and HNL. AILD showed a high proportion of TNF
      alpha positive T-lymphocytes, and in addition, the percentages of IL-2, IL-4, IL
      5, IL-6, IL-13 and INF-gamma positive T-lymphocytes were relatively higher than
      in other diseases. Our results supported the state of multiple hypercytokinemia
      typically seen in AILD and suggested that the source of the cytokines is the
      lymph nodes. Our results also suggested that multiple cytokine networks play an
      important role in the clinical and histopathological features of AILD. Modulation
      of the cytokine network may be the logical objective in future therapeutic
      strategies designed for AILD.

PMID- 10953976
TI  - Tumour necrosis factor gene polymorphisms in lymphoproliferative disease.
AB  - Tumour necrosis factor (TNF) alpha is involved in the pathogenesis of established
      lymphoproliferative disease. Serum levels of TNFalpha and its soluble receptors
      are above normal values in B-cell chronic lymphocytic leukaemia (B-CLL) and they
      are valuable prognostic markers in lymphoma patients. The production of TNFalpha
      is genetically controlled. Altered synthesis of TNFalpha has been associated with
      polymorphisms at the TNF gene cluster (i.e. TNFA, TNFB and LTB). In the present
      study, we evaluated the prevalence of the known high TNFalpha- and TNFbeta-
      producing alleles TNF1, TNF2 of the TNFA gene, TNFB1, TNFB2 alleles of the TNFB
      gene and of the polymorphic alleles TNFd1, d2, d3, d4 and d5 of the
      microsatellite TNFd in patients with B-CLL, non-Hodgkin's lymphoma (NHL) and
      Hodgkin's disease (HD). This study demonstrates that there is no difference in
      the frequency of the tested TNF alleles between normal controls and cohorts of
      patients with lymphoproliferative disease. These results indicate that TNF
      alleles are not genetic predisposing factors in the development of these
      diseases.

PMID- 10953977
TI  - A metalloproteinase inhibitor prevents acute graft-versus-host disease while
      preserving the graft-versus-leukaemia effect of allogeneic bone marrow
      transplantation.
AB  - Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the
      pathogenesis of graft-versus-host disease (GVHD). Several recent studies have
      shown that some metalloproteinase mediates TNF-alpha and FasL processing. We
      examined the ameliorating effect of a hydroxamic acid-based metalloproteinase
      inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a lethal
      acuteGVHD model in mice. The ameliorating effect of KB-R7785 was superior to that
      of anti-TNF-alpha antibody. We also examined the effect of KB-R7785, which we
      previously demonstrated a potent ameliorating effect on acute GVHD, on graft
      versus-leukemia (GVL) effect of allogeneic bone marrow transplantation (BMT).
      Administration of KB-R7785 without bone marrow cells and spleen cells (BMS).
      significantly prolonged the survival of IgE-producing B53 hybridoma cell
      inoculated (C57BL/6 x BALB/c) F1 (CBF1) mice by inhibiting the infiltration of
      B53 cells into the liver and spleen. Transplantation of B6 BMS without KB-R7785
      resulted in the death of most recipients due to acute GVHD while efficiently
      eliminating B53 cells. Administration of KB-R7785 along with B6 BMS resulted in
      50% survival of B53-inoculated CBF1 mice over 50 days without histological
      manifestations of acute GVHD or residual B53 cells. These results suggest that KB
      R7785 could be a potent therapeutic agent for GVHD, and indicate the beneficial
      effects of KB-R7785 that inhibit tumor infiltration and prevent acute GVHD while
      preserving the GVL effect of allogeneic BMT.

PMID- 10953978
TI  - Molecular epidemiology of EBNA-1 substrains of Epstein-Barr virus in
      posttransplant lymphoproliferative disorders which have infrequent p53 mutations.
AB  - Posttransplant lymphoproliferative disorders (PTLDs), which are highly associated
      with Epstein-Barr virus infection, have a low frequency of molecular genetic
      abnormalities. Recently it has been suggested certain EBV substrains may be
      associated with specific lymphoma subtypes. The goals of our study were two fold:
      1) to determine the prevalence of EBNA-1 substrains and prognostic utility in
      PTLD and 2) to determine the incidence of p53 gene mutations and p53 protein
      overexpression in 32 EBV-positive PTLD cases. Tumor DNA was sequenced to identify
      EBNA-1 substrains at codon 487 and p53 gene mutations in exons 5-8. The PTLD
      samples contained the following EBNA-1 substrains: P-thr in 17/32 (53%), P-ala in
      11/32 (34%), and V-leu in 4/32 (13%). More heterogeneity within major subtypes
      was seen in the PTLD cases than in the referral group. A second group of 25
      referral (non-PTLD) samples including infectious mononucleosis (6) and sequential
      EBV positive virology samples (19) contained P-thr in 17/25 (68%); P-ala in 2/25
      (8%); and V-leu in 6/25 (24%). In the 29 B-cell PTLD the time to presentation was
      an average of 13.3 months in the P-ala group, 16.6 months in the P-thr group, and
      40.6 months in the V-leu group: (p>0.05). There was no difference in survival in
      patients (median overall--60 months) between the three different substrains of
      EBNA-1 (Log rank test, p=0.39). One of 31 (4.1%) cases (a diffuse large cell B
      cell) had a p53 mutation. Seven of 31 (23%) cases (all B-cell), including the p53
      mutated case, had over-expression of p53 protein. We conclude EBNA-1 substrains
      vary in PTLD and suggest the pattern reflects the geographical incidence of
      substrains in the region. We also conclude p53 mutations are not a significant
      molecular genetic abnormality in PTLD.

PMID- 10953979
TI  - Generation of dendritic cells from human chronic myelomonocytic leukemia cells in
      fetal calf serum-free medium.
AB  - It is generally believed that the immune system plays a role not only in the
      acquisition of malignant diseases but also in the rejection of microscopic as
      well as established tumor cells. Failure of the immune system to eliminate tumor
      cells may be, among other factors, due to an insufficient presentation of tumor
      antigens. Dendritic cells (DCs), as professional antigen-presenting cells,
      therefore, may be therapeutically used to initiate or enhance immune responses in
      patients with malignancies. In this study we demonstrate that peripheral blood
      cells of patients with chronic myelomonocytic leukemia (CMML) can be induced to
      acquire DC characteristics. Upon culture with granulocyte-macrophage colony
      stimulating factor (GM-CSF) plus interleukin-4 (IL-4) plus tumor necrosis factor
      alpha (TNFalpha), CMML cells develop DC morphology and acquire the phenotypic
      characteristics of DCs. When a CD14+ cell population is used for DC generation, a
      homogeneous differentiation towards the DC lineage occurs similar to that,
      observed in normal peripheral blood monocytes. CMML-derived DCs are potent
      stimulators of the allogeneic mixed lymphocyte reaction (MLR) when compared with
      uncultivated cells. The demonstration of a deletion of the long arm of chromosome
      7, del(7)(q22), in 86% of highly enriched CD1a+ cells by fluorescence in situ
      hybridization (FISH) indicates the leukemic origin of generated DCs. In addition,
      we present data that generation of CMML-derived DCs is also possible under fetal
      calf serum-free conditions for a potential clinical use. These DCs may be used as
      a cellular vaccine to induce anti-tumor immunity in patients with CMML.

PMID- 10953980
TI  - Alterations of P53 and RB genes and the evolution of the accelerated phase of
      chronic myeloid leukemia.
AB  - Using the single-strand conformation polymorphism and heteroduplex analyses, the
      P53 and RB genes were analyzed in cell samples from twenty-eight patients with
      chronic myeloid leukemia (CML) both at diagnosis and at the onset of accelerated
      phase (AP) of the disease. No alterations of the P53 or RB genes were found in
      any of the chronic phase (CP) samples. Structural abnormalities of the P53 gene
      were observed in ten of twenty-eight AP samples within exons 4, 5, 7 and 9. Of
      the ten cases of AP disease with altered P53 genes, five patients also suffered
      from the deletion of the other allele. Alterations of the RB gene could be
      detected in six AP samples, and aberrant band patterns were found in the analysis
      of exons 2, 3, 4, 6, 7, 13, 14, 17, 21 and 26. Among the six AP samples with
      structural abnormalities of the RB gene, two showed the loss of the other allele.
      It is of note that alterations of both P53 and RB genes were observed in two AP
      samples. Our data strongly suggest that abnormalities of the P53 and RB genes and
      acceleration of CML are linked events in some cases of AP.

PMID- 10953981
TI  - Accumulation of sestamibi in lymphoma cell lines in vitro.
AB  - Although some authors have suggested that sestamibi imaging is useful in
      evaluation of patients with lymphoma, others have obtained equivocal results.
      This discrepancy has been further investigated in vitro using two patient-derived
      non-Hodgkin's lymphoma cell lines, OCI-Ly3 and OCI-Ly18. Sestamibi (0.2 MBq/ml)
      was added to a suspension of OCI-Ly3 or OCI-Ly18 cells and aliquots were removed
      over 1 h and centrifuged to determine cell-associated radioactivity. Further
      experiments studied the effect of addition of a P-glycoprotein (Pgp) modulator or
      alteration in plasma and/or mitochondrial membrane potentials. Accumulation of
      sestamibi reached plateau values within 30 min, but these values were 6-fold
      higher in OCI-Ly3 than in OCI-Ly18. Inhibition of Pgp function with GG918 or
      PSC833 did not affect OCI-Ly3 cells but increased accumulation in OCI-Ly18 cells
      3-fold, indicating a moderate level of Pgp. However, both cell lines responded
      similarly to membrane potential alterations: hyperpolarization of the
      mitochondrial membrane with nigericin had little effect on accumulation: in
      contrast, depolarization of the plasma membrane with an isotonic high potassium
      buffer reduced accumulation of sestamibi to 52% of control and additional
      depolarization of the mitochondrial membrane with valinomycin further reduced
      accumulation to 12% of control levels. These studies suggest that there can be
      wide differences in accumulation between cell lines, in part due to Pgp-mediated
      efflux, but that both of these cell lines have highly polarized mitochondria with
      little further capacity for hyperpolarization.

PMID- 10953982
TI  - Extranodal marginal zone B-cell lymphoma genotyping by Alu-polymerase chain
      reaction.
AB  - DNA amplification by polymerase chain reaction (PCR) with primers designed on the
      widely distributed Alu sequences allows the production of specific inter-Alu DNA
      fingerprints. Amplification of tumour and matched normal DNA can show differences
      due to genetic alterations within the tumour genome. We applied this approach to
      study low-grade extranodal marginal zone B-cell lymphoma (of MALT type). After
      digestion with restriction enzymes, DNA samples were separately amplified by PCR
      with three different Alu-primers. A comparison between the fingerprint pattern
      from lymphoma and normal samples was made. Inter-Alu bands differing between the
      two samples were excised from the gel, cloned and sequenced. Nine cases of low
      grade MALT-lymphomas have been analysed, giving seventeen different bands between
      tumour and normal. DNA sequence analysis showed identities for three of them with
      sequences available at the GenBank. The methodology of Alu-PCR to detect DNA
      based abnormalities, in addition or combination with RNA-based methods, is a
      powerful tool to identify candidate regions frequently altered in tumours. With
      the increased available genomic sequences through the Human Genome Project, there
      will be an increasing probability of picking up perfect homologies with these
      sequences using cloned differential Alu-PCR bands in BLAST searches through
      genome databases.

PMID- 10953983
TI  - Wilms' tumor gene expression by normal and malignant human B lymphocytes.
AB  - Very little is known about Wilms' tumor gene (WT1) expression in B cells and its
      importance for growth regulation and differentiation. We have investigated WT1
      expression in fresh B lymphocytes and in a panel of B-cell lines of normal and
      malignant origin, including both Epstein-Barr virus (EBV) genome negative and EBV
      carrying cell lines. WT1 is constitutively activated in all lymphoblastoid cell
      lines (LCL) derived from EBV immortalization of lymphocytes from normal donors in
      vitro. These cell lines are distinguished for the presence of activated B-cell
      markers and an unrestricted expression of viral latent genes. In contrast, WT1
      expression is abrogated in normal B lymphocytes and in all Burkitt tumor derived
      cell lines, irrespective of the EBV genome carrying status and their phenotype
      pattern. A single step RT-PCR for simultaneous detection of the four spliced
      transcript isoforms has been applied to confirm their expression. Analysis of
      variant relative proportions suggested the maintenance of a balanced expression
      of the isoforms in LCL, as reported in non tumorous tissues. These data, together
      with the evidence that the replication in vitro of lymphoblastoid cells is not
      affected by WT1 activation following viral immortalization, support the
      hypothesis that gene inactivation, in addition to disrupted alternate splicing,
      may play a role in growth control derangements.

PMID- 10953984
TI  - Acute myeloid leukemia, inversion 16, occurring in a patient with chronic
      lymphocytic leukemia.
AB  - The occurrence of acute myeloid leukemia (AML) in patients previously diagnosed
      with chronic lymphocytic leukemia (CLL) is rare. In most cases, AML develops
      after treatment of CLL and is thought to be therapy related; unfavorable
      karyotypes are often evident. Herein, we report a patient with a long-standing
      history of CLL who developed AML with cytogenetic analysis revealing inversion
      16. In keeping with the favorable prognosis of this abnormality, the patient has
      achieved a complete remission, which has been maintained for 13 months.

PMID- 10953985
TI  - Bone marrow necrosis in adult acute leukemia and non-Hodgkin's lymphoma.
AB  - Bone marrow necrosis is a rare finding in adult patients diagnosed with acute
      leukemia or non-Hodgkin's lymphoma. Previous reports have suggested that it is
      associated with a poor prognosis. It remains unclear however, whether
      improvements in patient care during the last decade have altered patient outcome.
      In a retrospective review of 581 bone marrow biopsies performed ante mortum on
      adult patients with acute leukemia or non-Hodgkin's lymphoma, we identified 10
      cases of bone marrow necrosis (5 acute myeloid leukemia, 5 non-Hodgkin's
      lymphoma). Severe bone pain, elevated serum lactate dehydrogenase levels and
      leukoerythroblastic peripheral blood smears were common presenting features.
      Despite treating 8 of the 10 patients with curative intent, only 2 patients
      remain alive and disease-free. This study confirms that bone marrow necrosis in
      adults with acute leukemia and non-Hodgkin's lymphoma is a rare ante mortum
      finding and confers a poor prognosis. Whether these patients would benefit from
      more intensive therapy such as hematopoietic stem cell transplantation remains to
      be clarified.

PMID- 10953986
TI  - Acute lymphoblastic leukemia presenting as acute hepatic failure in childhood.
AB  - We report a 7-year old white girl who was admitted because of acute severe
      hepatic failure. Her complete blood count revealed pancytopenia and a bone marrow
      aspiration was consistent with acute lymphoblastic leukemia (ALL). Blasts cells
      were positive for cytoplasmic CD3 and cell surface T-associated markers. Viral,
      metabolic, immune and toxic causes for hepatic failure were ruled out. Treatment
      pre-phase with prednisone was started and liver function tests clearly improved
      after one-week therapy. However, due to her hepatic insufficiency, daily
      etoposide was administered orally during 15 days. On day 33 complete remission
      was achieved and hepatic function was normal, except for an increase in the
      bilirubin level which normalized on day 72. She received our current treatment
      for intermediate risk ALL and is still receiving continuation phase therapy,
      currently, with normal liver function and good tolerance to chemotherapy + 8
      months after achieving complete remission.

PMID- 10953987
TI  - Atypical chronic myeloid leukaemia with trisomy 21 mosaicism as a sole
      chromosomal abnormality.
AB  - We present a 46-year-old patient with Ph-chromosome negative, bcr-negative
      chronic myeloid leukaemia (CML) in accelerated phase with a clonal trisomy 21 in
      the leukaemic blast cells. A rapid progress of disease with appearance of
      monocytosis is described, showing similar features to chronic myelomonocytic
      leukaemia (CMML). Heterogeneous characteristics and possible distinction of these
      two entities are discussed.

PMID- 10953988
TI  - Ca2+ channels, 'quantized' Ca2+ release, and differentiation of myocytes in the
      cardiovascular system.
AB  - The application of confocal microscopy to cardiac and skeletal muscle has
      resulted in the observation of transient, spatially localized elevations in
      [Ca2+]i, termed 'Ca2+ sparks'. Ca2+ sparks are thought to represent 'elementary'
      Ca2+ release events, which arise from one or more ryanodine receptor (RyR)
      channels in the sarcoplasmic reticulum. In cardiac muscle, Ca2+ sparks appear to
      be key elements of excitation-contraction coupling, in which the global [Ca2+]i
      transient is thought to involve the recruitment of Ca2+ sparks, each of which is
      controlled locally by single coassociated L-type Ca2+ channels. Recently, Ca2+
      sparks have been detected in smooth muscle cells of arteries. In this review, we
      analyse the complex relationship of Ca2+ influx and Ca2+ release with local,
      subcellular Ca2+ microdomains in light of recent studies on Ca2+ sparks in
      cardiovascular cells. We performed a comparative analysis of 'elementary' Ca2+
      release units in mouse, rat and human arterial smooth muscle cells, using
      measurements of Ca2+ sparks and plasmalemmal K(Ca) currents activated by Ca2+
      sparks (STOCs). Furthermore, the appearance of Ca2+ sparks during ontogeny of
      arterial smooth muscle is explored. Using intact pressurized arteries, we have
      investigated whether RyRs causing Ca2+ sparks (but not smaller 'quantized' Ca2+
      release events, e.g. hypothetical 'Ca2+ quarks') function as key signals that,
      through membrane potential and global cytoplasmic [Ca2+], oppose arterial
      myogenic tone and influence vasorelaxation. We believe that voltage-dependent
      Ca2+ channels and local RyR-related Ca2+ signals are important in
      differentiation, proliferation, and gene expression. Our findings suggest that
      'elementary' Ca2+ release units may represent novel potent therapeutic targets
      for regulating function of intact arterial smooth muscle tissue.

PMID- 10953989
TI  - Incidence and correlates of hypertension in the Atherosclerosis Risk in
      Communities (ARIC) study and the Monitoring Trends and Determinants of
      Cardiovascular Disease (POL-MONICA) project.
AB  - OBJECTIVE: The purpose of this research is to assess short-term blood pressure
      change and hypertension incidence, and identify correlates of incident
      hypertension in the USA and Poland. DESIGN AND METHODS: Population-based samples
      aged 45-64 years at enrollment from the Atherosclerosis Risk in Communities
      (ARIC) and the Pol-MONICA studies: including 3777 whites from Minneapolis,
      Minnesota, USA suburbs (urban), 3635 whites from Washington County, Maryland, USA
      (semi-rural) and 3109 blacks from Jackson, Mississippi, USA surveyed in 1987-1989
      and 1990-1992; and 389 persons from Warsaw, Poland (urban) and 322 from
      Tarnobrzeg Province, Poland (semi-rural) surveyed in 1987-1988 and 1992-1993.
      RESULTS: Age-standardized systolic and diastolic blood pressures at both screens
      were 9-20 and 5-9 mmHg higher in the Polish samples than in US blacks, who had
      higher levels than US whites. Age-adjusted annual hypertension incidence in both
      Polish male cohorts (6-8%) was higher than that in US white men (4%) and
      approaching that of US black men (7%); rates were also higher in Polish female
      cohorts (8-9%) than in US black women (8%), but nearly twice those in US white
      women (4%). Factors independently related to hypertension incidence included age,
      family history, smoking, baseline blood pressures and body mass index, and
      increase in body mass index and alcohol consumption between screenings. After
      adjustment for these factors, annualized hypertension incidence was similar in US
      white and Polish men (2.3 and 2.7%) compared with US black men (3.4%), and in US
      white and Polish women (1.5 and 1.3%) compared with US black women (3.9%).
      CONCLUSIONS: Despite substantial differences in blood pressure levels and age
      standardized hypertension incidence rates, the differences in incidence between
      Polish and US white men appear to be explained largely by differences in risk
      factors for hypertension.

PMID- 10953990
TI  - Adjustment for current weight and the relationship between birth weight and blood
      pressure in childhood.
AB  - OBJECTIVE: To determine the role of current weight in mediating the relationship
      between birth weight and blood pressure within the context of the 'fetal origins'
      hypothesis. DESIGN: Prospective cohort study of 2507 pregnant women and their
      singleton offspring, delivered live at term, in Perth, Western Australia between
      1989 and 1992. The study commenced at 16 weeks gestation with serial weight and
      blood pressure measurements recorded through early childhood. RESULTS: Inverse
      associations were found between birth weight and systolic blood pressure at ages
      1, 3 and 6. The effect of birth weight on systolic blood pressure at age 6
      reached statistical significance and was increased fourfold in magnitude to -2.3
      mmHg [95% confidence interval = (-3.3 to -1.3), P < 0.01] after adjustment for
      current weight. The interaction term for birth weight and current weight was not
      statistically significant. Including intermediate weights did not produce a
      statistically significantly better model but did increase the magnitude of the
      estimated regression coefficient of birth weight on blood pressure, and only the
      birth weight and current weight terms were significant CONCLUSIONS: Adjustment
      for current weight serves to highlight the relationship between birth weight and
      blood pressure in childhood. Nevertheless, birth weight, rather than birth weight
      adjusted for current weight, is still the relevant predictor of later blood
      pressure within the context of the 'fetal origins' hypothesis.

PMID- 10953991
TI  - Comparison of wrist blood pressure measurement with conventional sphygmomanometry
      at a cardiology outpatient clinic.
AB  - OBJECTIVE: Oscillometric measurement of blood pressure at the wrist is becoming a
      widely used method for detection of hypertension and its control by treatment.
      The objective of the present study was to evaluate accuracy and suitability of
      wrist measurement in a clinical routine setting. PATIENTS AND METHODS: A series
      of 333 consecutive patients admitted to our cardiology outpatient clinic were
      included. Blood pressure was measured at both upper arms according to World
      Health Organization-International Society of Hypertension guidelines.
      Oscillometric measurement was performed at the contralateral wrist
      simultaneously. Blood pressure readings were taken by an oscillometric device
      applied at the wrist ('Klock'; Industrielle Entwicklung Medizintechnik, Stolberg,
      Germany) and a conventional mercury sphygmomanometer applied at the upper arm.
      RESULTS: Seventy-eight patients were excluded due to differences in blood
      pressure > 5 mmHg between both upper arms or due to 'error' messages of the wrist
      device. The data of the remaining 255 patients (149 males; mean age, 65 +/- 13
      years; range, 18-95 years) are presented. Mean conventional blood pressure was
      significantly lower compared with the wrist device (137 +/- 20/80 +/- 11 mmHg
      versus 153 +/- 28/87 +/- 18 mmHg; P < 0.001 and P < 0.001). The mean difference
      was 16 +/- 25/6 +/- 17 mmHg. In clinical terms, differences in blood pressure
      exceeding +/-20/+/-10 mmHg reflecting classification of hypertension are
      considered important. Measurements of 101 (40%) patients were within these
      limits. Systolic readings of 110 (43%) and diastolic readings of 117 patients
      (46%) were beyond this scope. CONCLUSION: Due to low reliability of wrist blood
      pressure measurement, it cannot compete with the upper arm standard procedure. If
      ever, it should only be used if test readings in an individual comparing wrist
      and upper arm measurement show differences within a range of +/-20/+/-10 mmHg.

PMID- 10953992
TI  - Incidence and clinical relevance of RET proto-oncogene germline mutations in
      pheochromocytoma patients.
AB  - BACKGROUND: Autosomal dominant cancer syndrome--multiple endocrine neoplasia type
      2 (MEN 2), may exist more often than expected in patients with pheochromocytoma.
      Germline mutations identified recently in MEN 2 can be revealed by genetic
      screening. OBJECTIVE: To evaluate the frequency of RET (rearranged during
      transfection) mutations in patients with pheochromocytoma. DESIGN AND METHODS: We
      genetically screened germline mutations in the RET proto-oncogene and clinically
      re-evaluated patients with pheochromocytoma. A pentagastrin test and other
      biochemical studies were performed in all patients. SETTING: Department of
      Internal Medicine and Hypertension, The Medical University of Warsaw, Warsaw,
      Poland and the Department of Nephrology and Hypertension, Albert Ludwigs
      University, Freiburg, Germany. PARTICIPANTS: Seventy seven unselected patients
      with pheochromocytoma (19 men, 58 women, mean age: 51.55 +/- 1.5 years;
      pheochromocytoma confirmed histopathologically) out of 162 diagnosed and treated
      in the years 1957-1998 in the Department of Internal Medicine and Hypertension in
      Warsaw, Poland. The other 85 patients did not respond to the written invitation.
      MAIN OUTCOME MEASURES: The finding of RET mutations and diagnosis of MEN 2 in
      patients with pheochromocytoma. RESULTS: Genetic testing revealed germline
      mutations in the RET proto-oncogene in six patients (7.8%). All carriers had
      mutation of exon 11, codon 634: TGC to CGC. In four patients with this mutation,
      medullary thyroid carcinoma (MIC) was diagnosed and in three cases, surgically
      treated. Biochemical parameters: parathormone 31.88 +/- 2.87 pg/ml, calcitonin: 0
      min 0.23 +/- 0.14 ng/ml; 2 min 0.49 +/- 0.21 ng/ml; 5 min 0.48 +/- 0.21 ng/ml,
      metoxycatecholamines: 601.62 +/- 42.71 microg/24h, epinephrine: 1.94 +/- 0.17
      microg/24h, norepinephrine 13.96 +/- 1.3 microg/24h, carcinoembryonic antigen
      (CEA) 9.94 +/- 4.3 ng/ml. Ambulatory blood pressure monitoring (ABPM): systolic
      blood pressure (SBP): 116 +/- 1.9 mmHg, diastolic blood pressure (DBP): 73.7 +/-
      0.9 mmHg. Clinical, biochemical and imaging procedures did not reveal any
      recurrence of pheochromocytoma in the 77 patients studied. CONCLUSIONS: Patients
      with pheochromocytoma should be genetically screened for mutations of the RET
      proto-oncogene. These patients should undergo clinical screening for MEN 2. In
      addition, genetic studies can be useful for the screening of the families of the
      carriers.

PMID- 10953993
TI  - Comprehensive analysis of the renin-angiotensin gene polymorphisms with relation
      to hypertension in the Japanese.
AB  - BACKGROUND: Components of the renin-angiotensin (R-A) system have been repeatedly
      investigated as candidate genes for essential hypertension. In particular,
      suggestive or significant association has been detected in some studies for the
      angiotensinogen M235T, angiotensin I-converting enzyme I/D, angiotensin II type 1
      receptor A1166C, and aldosterone synthase C-344T polymorphisms, although the
      results remain inconclusive. OBJECTIVE AND METHODS: To evaluate the importance of
      these candidate genes for hypertension, we undertook an extensive association
      study in the Japanese. This case-control study was conducted in a total of 1476
      individuals using the four R-A gene polymorphisms. In the assessment of
      genotyping data, 843 hypertensive subjects were divided into three case subgroups
      according to severity of hypertension, while 633 normotensive subjects divided
      into two control subgroups by the age of enrollment. Each subgroup was further
      divided by sex. Subsequently, the presence of synergy (or gene-gene interaction)
      was evaluated among four R-A gene polymorphisms. RESULTS: No significant
      association was observed between the individual R-A gene polymorphisms and
      hypertension status in our case-control study. The results were almost unchanged
      when severity of hypertension, sex-specificity, and synergy were taken into
      account CONCLUSIONS: Despite a relatively large number of subjects, we did not
      find significant evidence for disease association in the Japanese population.
      Given confounding factors in the case-control strategy, the lack of association
      does not exclude the relevance of the R-A genes to hypertension. Further
      investigation needs to be performed in large-scale populations, where the use of
      not only hypertension status, but also 'intermediate' phenotypes would be useful.

PMID- 10953994
TI  - Reproducibility of radial pulse wave analysis in healthy subjects.
AB  - OBJECTIVE: To determine the reproducibility of parameters estimated by pulse wave
      analysis (PWA), mainly of central systolic blood pressure in the aorta (CSP),
      central systolic pressure-time index (CSPTI, area under the systolic part of the
      curve in the pressure-time graph per minute), and central augmentation index
      (CAI, pressure peak caused by wave reflection divided by pressure peak caused by
      ventricular ejection). METHODS: In 88 healthy subjects, aged 19-53 years, radial
      pulse wave was registered by two investigators on separate visits in a random
      sequence, twice during each visit RESULTS: Variability within and among subjects
      was significantly different for peripheral systolic pressure (PSP) and for all
      the above-mentioned parameters (P < 0.0001 by ANOVA for all). Variability within
      and between observers was tested by Bland-Altman plots; they did not show any
      trend for the variability to be dependent on the underlying mean value. PSP, CSP
      and CSPTI decreased significantly during one visit (by 4.6, 4.7 and 4.2%,
      respectively), PSP and CSP were higher at the first than at the second visit (by
      2.2, 2.2%, respectively, and not significant for CSPTI), and there were also
      significant interobserver differences in all the three parameters as one observer
      measured higher values (by 2.4, 3.2 and 6.0%, respectively). CAI did not change
      within and between visits; the same applied to the difference between PSP and CSP
      since these pressures always changed in parallel. CONCLUSIONS: PWA gives
      estimates of several parameters characterizing the pressure load of central
      circulation and the wave reflection. The reproducibility of CSP and CSPTI is
      similar to that of PSP. CAI and the difference between PSP and CSP is not
      influenced by order of measurement, of visit or by investigator. Therefore, CAI
      is a more stable parameter than PSP measured by an oscillometric device. Since
      these parameters may contribute to a better assessment of cardiovascular risk,
      PWA might be used in prospective studies.

PMID- 10953995
TI  - Enhanced vascular reactivity in the sympathectomized rat: studies in vivo and in
      small isolated resistance arteries.
AB  - OBJECTIVE: In the conscious rat, sympathectomy (6-hydroxydopamine pretreatment,
      100 mg/kg intraperitoneally, twice in the previous 5-6 days) induces, among
      various homeostatic modifications, the frequent occurrence of sudden and wide
      oscillations of blood pressure. Since one of the mechanisms underlying this, as
      yet unexplained, phenomenon may be an enhanced vascular reactivity, we tested the
      hypothesis that sympathectomized rats exhibit such a hyper-reactivity. We
      examined the response to a variety of vasoactive agents both in vivo (chronically
      instrumented conscious animals) and in vitro (small isolated resistance
      arteries). DESIGN AND METHODS: Wistar-Kyoto sympathectomized rats (6
      hydroxydopamine pretreatment, n = 19) and control rats (vehicle pretreatment, n =
      23) were studied. In conscious animals, concentration-blood pressure response
      curves to intra-venous bolus injections of vasopressin, phenylephrine and
      angiotensin II were obtained. In isolated vessels, concentration-wall tension
      response curves were obtained for norepinephrine, phenylephrine, vasopressin,
      serotonin and potassium. Vasodilator responses to acetylcholine (with or without
      L-NAME), bradykinin and sodium nitroprusside were also evaluated after
      precontraction with norepinephrine (mesenteric arteries) or vasopressin (cerebral
      arteries). RESULTS: In sympathectomized rats in vivo the pressor responses to
      vasopressin, phenylephrine and angiotensin II were significantly larger than in
      control rats, the difference amounting to 46.5, 40.2 and 57.1%, respectively (all
      P < 0.05). In vitro, the vascular reactivity of isolated cerebral arteries was
      similar in sympathectomized and control rats. In contrast, the mesenteric
      arteries showed significantly increased contractions in sympathectomized compared
      to control rats in response to norepinephrine, phenylephrine and vasopressin but
      not to serotonin and potassium, whereas the vasodilator responses to
      acetylcholine and sodium nitroprusside (but not to bradykinin and acetylcholine+L
      NAME) were reduced. CONCLUSIONS: In conclusion, we showed that sympathectomy
      produces complex alterations of vascular reactivity both in vivo and in isolated
      vessels, which shift the balance of the sensitivity of the vessel between
      vasoconstrictor and vasodilating agents towards an increased constriction. These
      results are unlikely to simply reflect denervation supersensitivity; their
      underlying receptor, post-receptor and/or contractile mechanisms are yet to be
      identified.

PMID- 10953996
TI  - Insulin and insulin-like growth factor-I promotes angiotensinogen production and
      growth in vascular smooth muscle cells.
AB  - BACKGROUND: Circulating insulin and insulin-like growth factor-I (IGF-I) levels
      are increased in patients with hypertension and insulin resistance. Since both
      hormones are known to have cell growth-promoting effects, they may contribute to
      the progression of vascular hypertrophy in patients with insulin resistance.
      Insulin-mediated activation of the vascular renin-angiotensin system (RAS)
      stimulates growth in cultured rat vascular smooth muscle cells (VSMC). OBJECTIVE:
      In order to evaluate the role of IGF-I-mediated activation of components of the
      tissue RAS, we examined the effect of IGF-I receptor stimulation on cell
      proliferation, and production of angiotensinogen in cultured VSMC. STUDY DESIGN:
      Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin
      mediated DNA synthesis were estimated by 3H-thymidine uptake (3H-TdR) with or
      without the angiotensin I converting enzyme inhibitor, captopril. Moreover,
      angiotensinogen released by the cells to the culture medium was determined by
      radioimmunoassay with or without the anti-IGF-I receptor antibody alphaIR3 or
      captopril. RESULTS: Both IGF-I and insulin increased 3H-TdR uptake by cultured
      rat VSMC (P < 0.05). Captopril blocked IGF-I and insulin-mediated 3H-TdR uptake (
      34.4 +/- 1.9% and -32.7 +/- 1.8%, P < 0.05, respectively). IGF-I increased the
      angiotensinogen level in the medium by 30.6 +/- 2.9% (P < 0.01). Insulin also
      stimulated angiotensinogen synthesis by 26.3 +/- 2.2% (P < 0.01). Captopril and
      alphaIR3 significantly suppressed angiotensinogen production stimulated by both
      IGF-I and insulin. CONCLUSIONS: These results indicate that IGF-I as well as
      insulin stimulates angiotensinogen production and growth in VSMC. Thus, both
      hormones may independently play a role in progression of the vascular hypertrophy
      and atherosclerosis in patients with hypertension and insulin resistance through
      activation of the tissue RAS.

PMID- 10953997
TI  - Involvement of the cyclic GMP pathway in the superoxide-induced IP3 formation in
      vascular smooth muscle cells.
AB  - OBJECTIVE: To investigate whether cGMP or cAMP signal pathway is indirectly
      involved in the effect of superoxide on the IP3 formation in vascular smooth
      muscle cells (SMC) from rat mesenteric arteries. METHODS: Cultured smooth muscle
      cells from rat mesenteric arteries were prelabelled with myo-(2-(3)H) inositol
      for evaluation of IP3 formation. Quantitative cAMP and cGMP levels were
      determined using cAMP [3H] or cGMP [125I] assay systems. RESULTS: In the present
      study, it was found that superoxide significantly inhibited the basal level of
      cGMP and also suppressed the sodium nitroprusside (SNP)-induced cGMP formation in
      SMCs from rat mesenteric arteries. The inhibitory effect of superoxide on basal
      level of cGMP was similar in the absence or presence of ODQ (a guanylyl cyclase
      inhibitor). Moreover, the superoxide-induced increase in IP3 formation was
      significantly inhibited by SNP or s-nitroso- n-acetylpenicillamine but was
      significantly potentiated by ODQ or KT5823 (a cGMP-dependent protein kinase
      inhibitor). Superoxide had no effect on the basal or on the forskolin-induced
      cAMP production and the inhibition of adenylyl cyclase or cAMP-dependent protein
      kinase did not affect the superoxide-enhanced IP3 formation. CONCLUSION: The
      decreased cross-inhibition of IP3 pathway by cGMP may contribute to the
      superoxide-enhanced IP3 formation in SMCs from mesenteric arteries. The cross
      talk between cGMP and IP3 pathways provides a novel mechanism for the signalling
      role of superoxide in vascular SMCs.

PMID- 10953998
TI  - Urokinase plasminogen activator enhances neointima growth and reduces lumen size
      in injured carotid arteries.
AB  - OBJECTIVES: Increases in urokinase plasminogen activator (uPA) have been reported
      in tissues undergoing remodelling, but its effects on the vessel intima formation
      are not known. We investigated its effects on carotid artery intima, media and
      lumen size, as well as smooth muscle cell (SMC) proliferation and migration in
      vivo. DESIGN AND METHODS: Carotid arteries of rats were distended with an
      inflated balloon catheter and uPA, or uPA-neutralizing antibodies were applied
      perivascularly in pluronic gel; control rats received vehicle. Carotid artery
      structure, cell migration and proliferation were assessed after 4 days by
      quantitative morphometry and immunohistochemistry. RESULTS: Four days after
      increasing vessel uPA, the intima/media ratio was double compared to that in
      control rats (both P < 0.05). The size of the lumen reduced by 75%, compared to
      the vehicle-treated vessels (P < 0.05). The elevation in uPA also increased SMC
      numbers in the intima and media, compared to the vehicle-treated vessels (both P
      < 0.05). Antibody neutralizing endogenous uPA attenuated the growth responses in
      the distended arteries, reduced neointimal SMC numbers by approximately 50% and
      prevented much of the reduction in lumen size. CONCLUSIONS: Thus, local increases
      in uPA in distended, injured arteries augment SMC migratory and proliferative
      responses, leading to increases in the thickness of the carotid artery intima and
      media and a reduction in lumen size; effects at least partially attributable to
      its proteolytic properties.

PMID- 10954000
TI  - Enhanced expression of Gi proteins in non-hypertrophic hearts from rats with
      hypertension-induced by L-NAME treatment.
AB  - OBJECTIVE: The objective of the present studies is to investigate if the enhanced
      expression of Gs alpha protein and their mRNA observed in various models of
      hypertensive rats is due to the expressed hypertrophy or hypertension. METHODS:
      Hypertension, in Sprague-Dawley rats was induced by the oral administration of
      the arginine analog N(omega)-nitro-L-arginine methyl ester (L-NAME) in their
      drinking tap water for a period of 4 weeks. The control rats were given plain tap
      water only. The levels of inhibitory guanine nucleotide regulatory proteins (Gi
      alpha-2, Gi alpha-3), stimulatory guanine nucleotide proteins (Gs alpha) and G
      beta proteins were determined by immunoblotting, whereas the levels of Gi alpha
      2, Gi alpha-3, Gs alpha and adenylyl cyclase type V enzyme mRNA were determined
      by Northern-blotting techniques. Adenylyl cyclase activity was determined by
      measuring [32P]cAMP formation from [alpha32P]ATP. RESULTS: The systolic blood
      pressure was enhanced in L-NAME-treated rats compared to control rats (190 +/-
      9.2 mmHg versus 121 +/- 6.3 mmHg); however, heart-to-body-weight ratio was not
      different in two groups. The levels of Gi alpha-2 and Gi alpha-3 proteins and
      their mRNA were significantly augmented in hearts from L-NAME-treated rats,
      however, the levels of Gs alpha and G beta were unaltered. In addition, the
      effect of low concentrations of GTPgammaS on forskolin (FSK)-stimulated adenylyl
      cyclase activity (receptor-independent functions of Gi alpha) was significantly
      enhanced in L-NAME-treated rats. However, the inhibitions of adenylyl cyclase
      exerted by oxotremorine, C-ANP(4-23) and angiotensin II (AII) (receptor-dependent
      function of Gi alpha) were completely attenuated in L-NAME-treated rats. On the
      other hand, cholera toxin stimulated GTP or GTPgammaS-sensitive adenylyl cyclase
      activity (Gs alpha function) to similar extent in control and L-NAME-treated
      rats, suggesting that Gs alpha functions were not altered by L-NAME treatment.
      However, the stimulatory effects of isoproterenol, glucagon, NaF on adenylyl
      cyclase were diminished in L-NAME-treated rats. In addition, FSK-stimulated
      enzyme activity was also diminished in L-NAME-treated rats without any changes in
      the mRNA levels of type V enzyme. CONCLUSIONS: These results suggest that L-NAME
      hypertensive rats that do not express cardiac hypertrophy exhibit enhanced
      expression of Gi alpha protein and associated adenylyl cyclase activity.

PMID- 10953999
TI  - Protective effect of inducible type nitric oxide synthase against intracellular
      oxidative stress caused by advanced glycation end-products in vascular smooth
      muscle cells from stroke-prone spontaneously hypertensive rats.
AB  - OBJECTIVE: A recent study demonstrated that free radicals were involved in the
      maintenance of hypertension in stroke-prone spontaneously hypertensive rats
      (SHRSP). However, the role of oxidative stress in hypertension and its related
      diseases in SHRSP remains unknown. On the other hand, advanced glycation end
      products (AGEs) accumulate progressively in the vasculature with ageing, and have
      been identified to be as relevant mediators for various vascular complications.
      To elucidate whether nitric oxide (NO) produced by inducible type NO synthase
      (iNOS) in vascular smooth muscle cells (VSMC) taken from SHRSP and Wistar-Kyoto
      rats (WKY) attenuate AGEs-induced oxidative stress, we investigated the effect of
      NO donors and iNOS-induction in VSMC on intracellular oxidant level caused by
      AGEs. METHODS: The cells preincubated with or without NO donor, S-nitroso-n
      acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1), IL-1beta and/or
      N(G)-monomethyl-L-arginine monoacetate (L-NMMA), were treated with AGEs, and the
      intracellular oxidant levels, total glutathione (GSH) levels, and gamma
      glutamylcysteine synthetase (GCS) mRNA were determined. We also determined the
      expression of an iNOS in VSMC from SHRSP and WKY. RESULTS: The intracellular
      oxidant level of VSMC was induced by AGEs in a dose-dependent manner. NO donor
      dose-dependently reduced AGEs-stimulated intracellular oxidant level. Treatment
      with IL-1beta reduced the AGEs-stimulated intracellular oxidant level through
      increased NO production, whilst inhibition of NO production by L-NMMA reduced the
      inhibitory effect of IL-1beta. We also confirmed that NO production as well as
      the expression of iNOS mRNA and the protein itself were significantly decreased
      in response to IL-1beta in VSMC from SHRSP compared with WKY. We also confirmed
      that total GSH levels, decreased by AGEs, were restored by stimulation with IL
      1beta. Increased GSH synthesis was due to enhanced expression of the rate
      limiting enzyme for GSH synthesis, GCS. These results indicate that NO release,
      produced by iNOS in VSMC in response to cytokines, might play a protective role
      against AGEs-stimulated oxidative stress in VSMC. This protective effect of NO is
      decreased in SHRSP compared to WKY.

PMID- 10954001
TI  - Different patterns of renal prostaglandins I2 and E2 in patients with essential
      hypertension with low to normal or high renin activity.
AB  - OBJECTIVE: Differences in renal synthesis between prostaglandins I2 and E2, and
      the relationships of the amounts synthesized to renin release were investigated
      in patients with essential hypertension. METHODS: Of 12 inpatients, six had low
      to normal plasma renin activity and six had high renin activity. Before and 30
      min after intravenous injection of aspirin D,L-lysine (18 mg/kg), abdominal
      aortic and renal venous plasma was sampled and assayed for renin activity, 6
      ketoprostaglandin F1alpha (as an index of prostaglandin I2), and prostaglandin
      E2. RESULTS: In patients with low to normal renin activity, mean +/- SD plasma
      levels of 6-keto-prostaglandin F1alpha were lower in the right and left renal
      veins (3.6 +/- 1.4 and 4.1 +/- 1.5 pg/ml, respectively) than in the aorta (5.5 +/
      2.0 pg/ml), but in the other patients, the levels in these veins (7.0 +/- 2.4
      and 6.5 +/- 1.5 pg/ml) were higher than in the aorta (5.4 +/- 0.9 pg/ml). Plasma
      prostaglandin E2 levels in both veins were higher than in the aorta in both
      groups and, at each site, the levels were similar in the two groups. Aspirin
      suppressed renin release in the patients with high renin activity. CONCLUSIONS:
      In patients with essential hypertension with low to normal renin activity, either
      less prostaglandin I2 than prostaglandin E2 is produced in the kidney or else
      more is metabolized there, and in such patients with high renin activity, the
      renal synthesis of prostaglandin I2, more than that of prostaglandin E2, seems to
      be related to the increased renin release.

PMID- 10954002
TI  - Regulation by sodium intake of type 1 angiotensin II receptor mRNAs in the kidney
      of Sabra rats.
AB  - OBJECTIVE: To study the relationship between the sensitivity to sodium content of
      the diet in terms of development of hypertension and the regulation of the
      expression of type 1 angiotensin II receptor subtypes by such a diet. METHODS:
      The expression of angiotensin II receptor subtype (AT1A and AT1B) mRNAs was
      studied by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)
      in the four zones of the kidneys of Sabra rats, sensitive or resistant to DOCA
      salt-induced hypertension (SBH/y and SBN/y, respectively). Rats were fed a high
      (8%) or normal (0.4%) NaCl diet. As vasopressin is known to be elevated in SBH/y
      rats and to be involved in DOCA-salt hypertension, we studied an additional group
      of SBH/y rats, fed a high sodium diet, enriched in water. RESULTS: With the
      absence of DOCA, SBH/y rats did not develop hypertension. The high sodium diet
      induced a greater fall in the plasma renin activity in the SBH/y (-95%) than in
      the SBN/y (-63%). In the cortex (C) and inner stripe (IS), the high sodium diet
      decreased AT1A and AT1B mRNAs in SBH/y and SBN/y, with a higher magnitude for
      SBH/y, than for SBN/y (C, -28 versus -20%; IS, -42 versus -20%). The addition of
      water to the high sodium diet lessened the effect of sodium in the C and IS,
      although the plasma renin activity (PRA) was not altered. CONCLUSION: A high
      sodium diet significantly decreases both AT1A and AT1B gene expression in two
      specific zones of the rat kidney containing the target cells of angiotensin II (C
      and IS). This down-regulation is organ-specific since it was observed in the
      kidney and adrenals, but not in the liver. Finally, SBH/y and SBN/y rats differ
      in the basal level of AT1 mRNA expression in the IS, and in the ability to
      modulate AT1 mRNA level under sodium intake.

PMID- 10954003
TI  - Chronic cyclooxygenase-2 inhibition blunts low sodium-stimulated renin without
      changing renal haemodynamics.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, is
      found in the macula densa of the renal cortex and is upregulated by dietary
      sodium restriction. Because of this discrete cortical localization, we
      hypothesized that COX-2 plays a role in the chronic stimulation of renin via the
      macula densa pathway. METHODS: We examined the effect of the selective COX-2
      inhibitor NS 398 in male Sprague-Dawley rats. RESULTS: A low sodium diet (0.02%
      NaCl) for 14 days elevated plasma-renin activity (PRA) nine-fold, from 6.1 +/-
      2.0 to 54.9 +/- 6.5 ng angiotensin I (Ang I)/ml per h (P < 0.0001). Selective COX
      2 inhibition with NS 398 had no effect on PRA in animals on normal sodium (5.1 +/
      1.3 ng Ang I/ml per h), but decreased PRA by 41% in sodium-restricted rats, to
      33.3 +/- 3.6 ng Ang I/ml per h (P < 0.05). Chronic treatment with NS 398 did not
      decrease renal renin content (31.8 +/- 1.8 versus 33.5 +/- 2.6 ng Ang I/ mg per
      h, with NS 398 versus controls), nor did it influence systemic blood pressure or
      renal haemodynamics. Neither urinary sodium excretion nor prostaglandin (PG)E2
      excretion was altered in rats given NS 398. Chronic treatment with the non
      selective COX inhibitor indomethacin during sodium restriction over 5 days
      reduced PRA by 35%, from 29.36 +/- 4.81, to 19.13 +/- 2.88 ng Ang I/ml per h (P <
      0.05). Indomethacin had no effect on blood pressure or renal blood flow but
      reduced urinary PGE2 excretion by 70%. CONCLUSIONS: One component of the chronic
      stimulation of PRA by dietary sodium restriction via the macula densa pathway
      appears to involve the induction of COX-2.

PMID- 10954004
TI  - Dihydropyridine calcium antagonists and renal function in hypertensive kidney
      transplant recipients.
AB  - OBJECTIVE: To investigate whether calcium antagonists are nephroprotective in
      hypertensive cyclosporine-treated renal allograft recipients. METHODS: We studied
      50 hypertensive and 17 normotensive renal transplants (eight females, nine males;
      14-54 years, mean age 38.8 +/- 3.5 years). Hypertensive patients were randomized
      to be treated with (+Ca; 11 females, 13 males; 20-65 years, mean age 43.1 +/- 3
      years) or without (-Ca; 15 females, 11 males; 25-60 years, mean age 41.3 +/- 2.5
      years) a calcium antagonist (nitrendipine or nifedipine). Additional
      antihypertensives were given stepwise according to a standardized protocol: beta1
      adrenoceptor blocker, diuretic alpha1-adrenoceptor blocker or vasodilator. Data
      were analysed at 0, 1, 2 and 3 years on an intention-to-treat basis. RESULTS:
      Hypertensive patients had a higher body mass index at 0/3 years (23.7 +/-
      0.6/25.1 +/- 0.6 kg/m2) than normotensive patients (22.2 +/- 0.6/22.1 +/- 0.7
      kg/m2). During the study, blood pressure in normotensive transplants was always
      slightly, but not significantly, lower than that of transplants with treated
      hypertension. There was no difference between the groups (+Ca) and (-Ca). Cr51
      ethylenediaminetetracetic acid (EDTA) clearance (0/2 years) was 58 +/- 4/57 +/- 6
      ml/min in normotensives, 52 +/- 4/47 +/- 4 ml/min in hypertensives (+Ca) and 47
      +/- 4/49 +/- 6 ml/min in hypertensives (-Ca). Proteinuria (0/3 years) was 0.16 +/
      0.04/0.15 +/- 0.02 g/24 h in normotensive, 0.26 +/- 0.08/0.23 +/- 0.05 g/24 h in
      hypertensives (+Ca) and 0.26 +/- 0.07/0.22 +/- 0.05 g/24 h in hypertensives (
      Ca). CONCLUSIONS: Post-transplant hypertension is associated with higher body
      mass index and poor renal function. No difference in the course of Cr51-EDTA
      clearance, serum creatinine, proteinuria or blood pressure was observed between
      groups treated with or without calcium antagonists. Calcium antagonists and
      conventional antihypertensive treatment have the same nephroprotective effect in
      hypertensive renal transplants, when treatment is started 3 months after
      transplantation.

PMID- 10954005
TI  - Evaluation of brain natriuretic peptide as marker of left ventricular dysfunction
      and hypertrophy in the population.
AB  - OBJECTIVE: To evaluate brain natriuretic peptide (BNP) as marker of left
      ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610
      middle-aged subjects (50-67 years) who were further characterized with respect to
      hemodynamic and anthropometric parameters and by echocardiography. RESULTS: Left
      ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and
      medication with beta adrenergic receptor blockers were significant and
      independently correlated with BNP (multivariate analysis, P < 0.05 each). As
      compared to subjects with normal LV function and mass-index (control), subjects
      with LV dysfunction (LV fractional shortening < 28%) or hypertrophy (LV mass
      index > 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased
      BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus
      control, P < 0.0001) was similar in magnitude to that associated with LV
      dysfunction (n = 39, +98% versus control, P < 0.03). These increases were
      markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional
      shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the
      presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive
      values of BNP varied considerably with the degree of LV dysfunction and the
      presence or absence of concomitant LV hypertrophy. With 0.81, the highest area
      under the receiver operator characteristic curve was obtained for the detection
      of severe LV dysfunction and concomitant hypertrophy and sensitivity,
      specificity, positive and negative predictive value for this condition were 71,
      86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml. CONCLUSIONS: The
      current study provides new insight into regulation and diagnostic value of BNP in
      middle-aged subjects and demonstrates important independent effects of LV
      function and mass upon BNP plasma concentrations. Although measurement of BNP
      cannot be recommended for the detection of marginally impaired LV function in the
      population, it may be helpful to suggest or exclude severe LV dysfunction with
      concomitant hypertrophy.

PMID- 10954006
TI  - Left ventricular wall stresses and wall stress-mass-heart rate products in
      hypertensive patients with electrocardiographic left ventricular hypertrophy: the
      LIFE study. Losartan Intervention For Endpoint reduction in hypertension.
AB  - OBJECTIVE: Left ventricular (LV) hypertrophy on echocardiogram (ECG) strongly
      predicts coronary heart disease events, but the mechanisms linking increased LV
      mass to ischemic vascular events is uncertain. DESIGN: Variables related to
      myocardial oxygen demand were compared among normotensive adults and patients
      with mild and more severe hypertension, and among groups of moderately
      hypertensive patients with target organ damage in relation to gender, LV geometry
      and LV systolic function. SETTING: The Losartan Intervention For Endpoint
      reduction in hypertension (LIFE) trial, in which hypertensive patients with ECG
      LV hypertrophy (Cornell voltage-duration product, > 2440 mm x ms and/or SV1 +
      RV(5-6) > 38 mm) were randomized to > or = 4 years double-blinded treatment with
      losartan or atenolol. PATIENTS/PARTICIPANTS: A total of 964 LIFE participants
      enrolled in an echocardiographic substudy, and groups of 282 employed
      hypertensive and 366 apparently normal adults. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: ECG LV parameters contributing to myocardial oxygen demand (wall
      stresses, LV mass, heart rate and wall stress-mass-heart rate products). RESULTS:
      In both women and men, stepwise increases from reference subjects to employed
      hypertensives to LIFE patients were observed for LV wall stresses, mass and
      stress-mass-heart rate products. LIFE men patients had slightly higher wall
      stresses and significantly higher triple products than women. Wall stresses were
      increased in patients with normal LV geometry, eccentric or concentric
      hypertrophy; triple products were about three and two times normal with eccentric
      and concentric hypertrophy, with smaller increases in other geometric groups.
      Patients with decreased LV fractional shortening had two times normal end
      systolic stresses and three or four times normal triple products; smaller
      increases in stresses and triple products occurred with decreased LV midwall
      function. CONCLUSIONS: Hypertensive patients with ECG LV hypertrophy have
      increased LV wall stresses and stress-mass-heart rate products, suggesting a
      contribution of high myocardial oxygen demand to increased risk in such patients.
      Particularly high stresses and triple products were associated with
      echocardiographic LV hypertrophy, and subnormal LV chamber and midwall function.

PMID- 10954009
TI  - Excess mortality associated with increased pulse pressure among middle-aged men
      and women is explained by high systolic blood pressure.

PMID- 10954007
TI  - Pilot study of combined blockade of the renin-angiotensin system in essential
      hypertensive patients.
AB  - BACKGROUND: Additive hemodynamic effects of combined blockade of the renin
      angiotensin system by an angiotensin I converting enzyme inhibitor and an
      angiotensin II antagonist have been observed in sodium-depleted normotensive
      volunteers and in patients with congestive heart failure. OBJECTIVE: To
      investigate whether the same additive hemodynamic effects occur in patients with
      hypertension and to verify the safety of such an approach. DESIGN: Multicenter,
      randomized, double-blind, parallel-group, pilot study. PATIENTS: 177 patients
      with mild-to-moderate hypertension [diastolic blood pressure (DBP): 95-115 mmHg
      after a 4-week placebo run-in period] were included in the study. INTERVENTION:
      Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily
      was administered for 6 weeks. The effects of this therapeutic regimen was
      compared with similar groups of patients who received either 50 mg losartan daily
      or 10 mg enalapril daily. MAIN OUTCOME MEASURES: 24-hour ambulatory mean DBP and
      clinic DBP measured at trough after 6 weeks of treatment. RESULTS: 24-hour
      ambulatory mean DBP did not significantly differ between treatment groups
      although the combination tended to lower BP more. The combination therapy was
      more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg
      [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012], and more effective than
      enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28
      patients, higher plasma active renin and angiotensin I levels during blockade by
      the combination therapy were observed. This finding confirmed that the
      combination of the two agents inhibited the renin-angiotensin system to a greater
      extent than did either agent alone. CONCLUSION: A combination of 10 mg enalapril
      daily and 50 mg losartan daily safely induces a supplementary, although modest,
      fall in clinic DBP in patients with mild-to-moderate essential hypertension.

PMID- 10954008
TI  - Serum uric acid, diuretic treatment and risk of cardiovascular events in the
      Systolic Hypertension in the Elderly Program (SHEP).
AB  - OBJECTIVE: To assess longitudinally the association of serum uric acid and its
      change due to diuretic treatment with cardiovascular events in hypertensive
      patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of
      hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or =
      60 years, with isolated systolic hypertension, randomized to placebo or
      chlorthalidone, with the addition of atenolol or reserpine if needed, were
      observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events,
      coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event
      rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person
      years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV,
      41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR),
      of cardiovascular events for the highest quartile of serum uric acid versus the
      lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was
      not affected by baseline serum uric acid. After randomization, an increase of
      serum uric acid < 0.06 mmol/l (median change) in the active treatment group was
      associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those
      with a serum uric acid increase > or = 0.06 mmol/l. This difference was not
      explained by blood pressure effects. Those with a serum uric acid increase > or =
      0.06 mmol/l in the active treatment group had a similar risk of coronary events
      as the placebo group. CONCLUSIONS: Serum uric acid independently predicts
      cardiovascular events in older persons with isolated systolic hypertension.
      Monitoring serum uric acid change during diuretic treatment may help to identify
      patients who will most benefit from treatment.

PMID- 10954010
TI  - Plasma nitric oxide concentrations are elevated in insulin-resistant healthy
      subjects.
AB  - The goal of this study was to compare plasma nitric oxide (NO) concentrations in
      healthy subjects, defined as either insulin-resistant or insulin-sensitive on the
      basis of the plasma insulin response to a 75-g oral glucose challenge. For this
      purpose, 404 healthy subjects were divided into quartiles on the basis of the
      plasma insulin response to glucose, and 49 individuals were selected from the
      quartile with the lowest insulin response and 49 from the quartile with the
      highest insulin response. The two groups of 49 each were selected to be
      essentially identical in terms of age, gender distribution, body mass index
      (BMI), and waist to hip ratio (WHR). The quartile with the greatest insulin
      response also had a significantly higher plasma glucose response to oral glucose,
      faster heart rate, higher blood pressure, and the combination of higher
      triglyceride and lower high-density lipoprotein (HDL) cholesterol concentrations.
      In addition to the latter changes, previously shown to be associated with
      hyperinsulinemia, NO concentrations were also higher in the hyperinsulinemic
      group. It is speculated that this increase in the NO concentration in
      hyperinsulinemic and presumably insulin-resistant, subjects represents a
      compensatory effort to overcome the untoward effects of insulin resistance and/or
      hyperinsulinemia.

PMID- 10954012
TI  - D-tagatose, a stereoisomer of D-fructose, increases blood uric acid
      concentration.
AB  - D-Fructose has been found to increase uric acid production by accelerating the
      degradation of purine nucleotides, probably due to hepatocellular depletion of
      inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The
      hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater
      than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate
      is slower than the degradation of D-fructose-1-phosphate. We tested the effect of
      30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic
      parameters in 8 male subjects by a double-blind crossover design. Both the peak
      concentration and 4-hour area under the curve (AUC) of serum uric acid were
      significantly higher after D-tagatose compared with either 30 g D-fructose or
      plain water. The decline in serum Pi concentration was greater at 50 minutes
      after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to
      D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the
      glycemic and insulinemic responses to a meal that was consumed 255 minutes after
      its administration. Moreover, both fructose and D-tagatose increased plasma
      concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The
      metabolic effects of D-tagatose occurred despite its putative poor absorption.

PMID- 10954011
TI  - Induction of insulin resistance in human skeletal muscle cells by downregulation
      of glycogen synthase protein expression.
AB  - Glycogen synthase (GS) is the rate-limiting enzyme controlling nonoxidative
      glucose disposal in skeletal muscle. A reduction in GS activity and an impaired
      insulin responsiveness are characteristic features of skeletal muscle in type 2
      diabetes. These properties also exist in human skeletal muscle cell cultures from
      type 2 diabetic subjects. To determine the effect of an isolated reduction in GS
      on skeletal muscle insulin action, cultures from nondiabetic subjects were
      treated with antisense oligonucleotides (ODNs) to GS to interfere with expression
      of the gene. Treatment with antisense ODNs reduced GS protein expression by 70%
      compared with control (scrambled) ODNs (P < .01). GS activity measured at 0.01
      mmol/L glucose-6-phosphate (G-6-P) was reduced by antisense ODN treatment. The
      insulin responsiveness of GS was impaired. Insulin also failed to stimulate
      glucose incorporation into glycogen after antisense ODN treatment. The cellular
      glycogen content was lower in antisense ODN-treated cells compared with control
      ODN. The insulin responsiveness of glucose uptake was abolished by antisense ODN
      treatment. Thus, reductions in GS expression in human skeletal muscle cells lead
      to impairments in insulin responsiveness and may play an important role in
      insulin-resistant states.

PMID- 10954013
TI  - Energy restriction dilutes the changes related to dietary fat type in membrane
      phospholipid fatty acid composition in rats.
AB  - To investigate liver cell membrane phospholipid (PL) fatty acid (FA) composition
      in response to the consumption of different types of dietary fat and graded
      levels of energy intake, rats were fed for 10 weeks on a diet containing either
      fish oil, safflower oil, or beef tallow. Within each dietary fat group, subgroups
      were either provided free access to food or energy-restricted to 85% or 70% of
      the ad libitum intake by reducing the dietary carbohydrate content while keeping
      other macronutrient intakes constant. Higher (P < .05) proportions of
      docosahexaenoic acid, linoleic acid, and monounsaturated FA were observed in the
      membrane PL of the fish oil, safflower oil, and beef tallow groups, respectively,
      resembling the FA composition in the diets. However, such modifications of
      dietary FA composition in, membrane PL FA were influenced by body energy status.
      The higher docosahexaenoic acid and total n-3 FA content in phosphatidylcholine
      (PC), sphingomyelin (SPH), and phosphatidylserine (PS) of the ad libitum fish oil
      group compared with the other dietary groups no longer existed when energy supply
      was restricted. Therefore, reducing energy intake tended to dilute the changes of
      membrane PL FA composition occurring as a function of dietary FA composition.
      These data suggest that the influence of dietary fat type on cellular structure
      and perhaps function becomes increasingly important with progressively positive
      energy balance.

PMID- 10954014
TI  - Increased responses of glucagon and glucose production to hypoglycemia with
      intraperitoneal versus subcutaneous insulin treatment.
AB  - The study aim was to investigate the effect of the route of insulin treatment on
      the glucagon and glucose production (GP) responses to hypoglycemia in the
      diabetic rat. Experiments were performed in 4 groups of rats: (1) streptozotocin
      (STZ)-induced diabetic, untreated (D, n = 7), (2) diabetic treated with
      subcutaneous insulin (DSC, n = 8), (3) diabetic treated with intraperitoneal
      insulin (DIP, n = 6), and (4) normal control (N, n = 10). Slow-release insulin
      implants were used in DSC and DIP rats for 10 to 14 days (3 U/d). A
      hyperinsulinemic (120 pmol x kg(-1) x min(-1) insulin)-hypoglycemic (glycemia =
      2.5 +/- 0.1 mmol/L) clamp following an isoglycemic basal period was performed in
      5-hour fasted rats. Basal plasma glucose was normalized in both DSC and DIP rats;
      however, in DSC but not DIP rats, glucose normalization required peripheral
      hyperinsulinemia. Tracer-determined GP, which was elevated in D rats, was
      completely normalized in DIP but only partially corrected in DSC rats. Basal
      glucagon levels were similar in all groups. During hypoglycemia, GP was
      suppressed in D rats (delta, -28.9 +/- 5.0 micromol x kg(-1) x min(-1),
      moderately increased in DSC rats (delta, 6.1 +/- 5.6, P < .01 v D), but markedly
      increased in DIP and N rats (delta, 34.5 +/- 4.5 for DIP and 16.8 +/- 2.8 for N;
      P < .01 vD, P < .05 for DIP v DSC or N). Plasma glucagon increased 6-fold in N
      (945 +/- 129 pg/mL), only doubled in D (424 +/- 54), and tripled in DSC (588 +/-
      83), but increased 5-fold in DIP rats (1,031 +/- 75, P < .05 v D and DSC). We
      conclude that in STZ-diabetic rats, (1) intraperitoneal but not subcutaneous
      insulin treatment normalizes basal GP, and (2) intraperitoneal insulin treatment
      as compared with subcutaneous treatment alleviates peripheral hyperinsulinemia
      and results in increased glucagon and GP responses to hypoglycemia.

PMID- 10954015
TI  - T-1095, a renal Na+-glucose transporter inhibitor, improves hyperglycemia in
      streptozotocin-induced diabetic rats.
AB  - The effect of T-1095, an inhibitor of renal glucose reabsorption, on
      hyperglycemia and the expression of Na+-glucose cotransporters (SGLTs) and
      facilitative glucose transporter 2 (GLUT2) in streptozotocin (STZ)-induced
      diabetic rats was examined. There was an elevation of blood glucose, hemoglobin
      A1c (HbA1c), kidney weight, and urinary excretion of both glucose and albumin in
      STZ rats. Administration of 0.03% and 0.1% (wt/wt diet) T-1095 to STZ rats for 4
      weeks improved the hyperglycemia and dose-dependently decreased HbA1c. Moreover,
      treatment with 0.1% (wt/wt diet) T-1095 in STZ rats for 8 weeks not only reduced
      blood glucose and HbA1c, levels but also prevented the elevation of urinary
      albumin levels and kidney weight and the development of epithelial vacuolation.
      The expression of renal SGLT2, a major glucose transporter in the kidney, was not
      different in normal, STZ, and T-1095-treated STZ rats. In contrast, the elevated
      renal GLUT2 level in STZ rats was suppressed by T-1095. These data suggest that T
      1095 improves hyperglycemia by suppressing the renal reabsorption of glucose,
      which results in a suppression of the development of functional and histological
      changes and abnormal expression of GLUT2 in the kidney.

PMID- 10954016
TI  - Effects of advanced glycation end-product inhibition and cross-link breakage in
      diabetic rats.
AB  - The accelerated formation of advanced glycation end-products (AGEs) due to
      elevated glycemia has repeatedly been reported as a central pathogenic factor in
      the development of diabetic microvascular complications. The effects of a novel
      inhibitor of AGE formation, NNC39-0028 (2,3-diaminophenazine), and a breaker of
      already formed AGE cross-links, N-phenacylthiazolium bromide (PTB), were
      investigated in streptozotocin-diabetic female Wistar rats. Diabetes for 24 weeks
      resulted in decreased tail collagen pepsin solubility, reflecting the formation
      of AGE cross-linking. Collagen solubility was significantly ameliorated by
      treatment with NNC39-0028, whereas PTB had no effect. Increased urinary albumin
      excretion (UAE) in diabetic rats was observed in serial measurements throughout
      the study period, and was not reduced by any treatment. Vascular dysfunction in
      the eye, measured as increased clearance of 125I-albumin, was induced by
      diabetes. NNC39-0028 did not affect this abnormality. This study demonstrated a
      pharmacological inhibition of collagen solubility alterations in diabetic rats
      without affecting diabetes-induced pathophysiology such as the increase in UAE or
      albumin clearance. Treatment with PTB, a specific breaker of AGE cross-links, had
      no effects in this study.

PMID- 10954017
TI  - The role of the body mass index and triglyceride levels in identifying insulin
      sensitive and insulin-resistant variants in Japanese non-insulin-dependent
      diabetic patients.
AB  - Using the minimal model approach shown by Bergman, our group had previously shown
      2 variants among non-obese mildly diabetic patients, one with normal insulin
      sensitivity and the other with insulin resistance. The present study examines
      whether these 2 variants exist in the ordinary Japanese non-insulin-dependent
      diabetes mellitus (NIDDM) population and compares the clinical profile between
      the 2 discrete forms of NIDDM. In addition, we investigated the factors
      responsible for insulin resistance observed in Japanese NIDDM populations. One
      hundred eleven untreated Japanese NIDDM subjects (fasting glucose < 10 mmol/L)
      were assessed for insulin action (homeostasis model assessment [HOMA-IR] =
      fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5) and the
      fasting lipid profile. Sixty percent of these patients had normal insulin
      sensitivity (HOMA-IR < 2.5). The insulin-resistant patients had higher serum
      cholesterol (188.1 +/- 5.2 v 182.2 +/- 3.9 mg/dL, P> .05) and low-density
      lipoprotein (LDL) cholesterol (501.2 +/- 16.7 v 469.4 +/- 14.8 mg/dL, P > .05)
      than the insulin-sensitive patients, but the difference was not statistically
      significant. In contrast, the former group had a significantly higher body mass
      index ([BMI] 26.6 +/- 0.8 v 21.7 +/- 0.4 kg/m2, P < .0001) and higher serum
      triglycerides (181.0 +/- 16.4 (range, 79 to 545) v 95.1 +/- 4.1 (range, 36 to
      204) mg/dL, P < .0001) and lower high-density lipoprotein (HDL) cholesterol (47.2
      +/- 1.7 v 58.2 +/- 2.5 mg/dL, P < .005) than the latter group. HOMA-IR was
      related to the BMI. Fifteen of 17 (88%) NIDDM patients with a BMI greater than
      27.0 were insulin-resistant, whereas 35 of 38 (92%) NIDDM patients with a BMI
      less than 21.5 were insulin-sensitive. In the midrange BMI (21.5 to 27.0 kg/m2),
      patients were equally likely to be insulin-resistant or insulin-sensitive.
      Analysis of the midrange BMI group showed that HOMA-IR was associated with serum
      triglycerides (P < .0001) but not with the BMI. These data suggest the following
      conclusions: (1) Japanese NIDDM patients can be classified into 2 populations,
      one with normal insulin sensitivity and the other with insulin resistance; (2)
      NIDDM patients with normal insulin action have a low cardiovascular disease risk
      factor, whereas those with insulin resistance have a markedly increased
      cardiovascular disease risk factor; and (3) the BMI and serum triglyceride level
      per se are associated with insulin action in Japanese NIDDM populations.

PMID- 10954018
TI  - Fatty acid-mediated activation of vascular endothelial cells.
AB  - Vascular endothelial cell activation and dysfunction are critical early events in
      atherosclerosis. Selected dietary lipids (eg, fatty acids) may be atherogenic by
      activating endothelial cells and by potentiating an inflammatory response. Due to
      their prooxidant property, unsaturated fatty acids may play a critical role in
      endothelial cell activation and injury. To test this hypothesis, porcine
      endothelial cells were exposed to 18-carbon fatty acids differing in the degree
      of unsaturation, ie, 90 micromol/L stearic (18:0), oleic (18:1n-9), linoleic
      (18:2n-6), or linolenic acid (18:3n-3) for 6 to 24 hours and/or tumor necrosis
      factor alpha ([TNF-alpha] 500 U/L) for up to 3 hours. Compared with control
      cultures, treatment with 18:0 and 18:2 decreased glutathione levels, suggesting
      an increase in cellular oxidative stress. Both 18:2 and 18:0 activated the
      transcription factor nuclear factor kappaB (NF-kappaB) the most and 18:1 the
      least. This NF-kappaB-dependent transcription was confirmed in endothelial cells
      by luciferase reporter gene assay. The fatty acid-mediated activation of NF
      kappaB was blocked by preenrichment of the cultures with 25 micromol/L vitamin E.
      All fatty acids except 18:1 and 18:3 increased transendothelial albumin transfer,
      and 18:2 caused the most marked disruption of endothelial integrity.
      Preenrichment of endothelial cells with 18:2 followed by exposure to TNF-alpha
      resulted in a 100% increase in interleukin-6 (IL-6) production compared with TNF
      alpha exposure alone. In contrast, cellular preenrichment with 18:0, 18:1, or
      18:3 had no effect on TNF-alpha-mediated production of IL-6. Cellular release of
      radiolabeled arachidonic acid (20:4) was markedly increased only by cell exposure
      to 18:2 and 18:3, and the release of 20:4 appeared to be mainly from the
      phosphatidylethanolamine fraction. These data suggest that oleic acid does not
      activate endothelial cells. Furthermore, linoleic acid and other omega-6 fatty
      acids appear to be the most proinflammatory and possibly atherogenic fatty acids.

PMID- 10954019
TI  - A genetic study of sex hormone--binding globulin measured before and after a 20
      week endurance exercise training program: the HERITAGE Family Study.
AB  - Familial aggregation and a major gene effect were assessed for baseline serum sex
      hormone-binding globulin (SHBG) levels and the response (post-training minus
      baseline) to a 20-week endurance training program in a selected sample of 428 non
      obese nonhypertensive individuals from 99 white families who were sedentary at
      baseline in the HERITAGE Family Study. Baseline SHBG levels were not normally
      distributed, and were therefore logarithmically transformed prior to genetic
      analyses. In a sample without postmenopausal mothers, maximal (genetic and
      familial environmental) heritabilities were 50% averaged across sexes, 73% in
      men, 50% in women, and 31% in men versus women for the age-body mass index (BMI)
      adjusted baseline. The estimate reached 64% when the baseline was further
      adjusted for the effects of estradiol, fasting insulin, and testosterone levels.
      For the response to training, no sex difference was found and the heritability
      reached about 25% to 32%. Segregation analysis was separately performed in the
      whole sample and in the sample without postmenopausal mothers. In addition to a
      multifactorial effect for both the baseline and the response to training, a major
      effect for the baseline appeared to be familial environmental in origin, whereas
      a major effect for the response to training was Mendelian in nature. The major
      gene effect for the response to training in the whole sample was undetectable in
      the sample without postmenopausal mothers, and it is therefore possible that the
      postmenopausal mothers, characterized by decreased sex hormones with or without
      estrogen replacement therapy for menopause, produced some confounding effects. In
      addition, the reduced sample size might also be a plausible candidate
      explanation. The novel finding in this study is that baseline SHBG levels and the
      response to training were influenced by a multifactorial effect with sex
      difference for the baseline. The response to training appeared to be additionally
      influenced by a single recessive locus that is independent of baseline SHBG
      levels.

PMID- 10954020
TI  - Tumor necrosis factor alpha gene G-308A polymorphism in the metabolic syndrome.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine
      constitutively produced by adipose tissue that may mediate insulin resistance.
      Studies in Caucasian subjects have suggested that the G-308A transition in the 5'
      region of the TNF-alpha gene may be associated with insulin resistance and
      obesity. These factors have been proposed to underlie the clustering of type 2
      diabetes, hypertension, and dyslipidemia found in the metabolic syndrome, the
      prevalence of which is reaching epidemic proportions in Hong Kong Chinese. We
      investigated the association of this gene polymorphism with the components of the
      metabolic syndrome including the lipid profile, as well as with the indices of
      obesity and insulin resistance as measured by the insulin-glucose product, in 440
      Chinese subjects (healthy [27.5%] and overlapping groups with type 2 diabetes
      [54.1%], hypertension [38.8%], dyslipidemia [39.3%], or obesity [39.5%]). The
      frequency of the mutant A allele was 7.4% in 121 healthy controls and 9.0% in the
      total population. The mutation was not associated with any component of the
      metabolic syndrome or with the prevalence of albuminuria and retinopathy in these
      subjects. Furthermore, there was no difference in anthropometric measures,
      insulin resistance, or lipid levels between subjects with the GG genotype and
      those with the mutant allele. In summary, the TNF-alpha gene G-308A polymorphism
      is unlikely to play an important role in the development of these disorders in
      this population.

PMID- 10954021
TI  - Accumulation of cystathionine, cystathionine ketimine, and perhydro-1,4
      thiazepine-3,5-dicarboxylic acid in whole brain and various regions of the brain
      of D, L-propargylglycine-treated rats.
AB  - Experimental cystathioninuria was induced in rats by administration of the
      cystathionine gamma-lyase inhibitor, D,L-propargylglycine. The cystathionine
      metabolites, cystathionine ketimine (CK) and perhydro-1,4-thiazepine-3,5
      dicarboxylic acid (PHTZDC), were identified in whole brain and various regions of
      the brain in D,L-propargylglycine-treated rats. The concentration of CK and
      PHTZDC in whole brain and various regions of the brain increased gradually after
      administration of D,L-propargylglycine, and reached the highest value at about 20
      hours. CK and PHTZDC accumulated in whole brain and various regions of the brain
      in proportion to the amount of accumulated cystathionine after D,L
      propargylglycine administration. The concentration of these compounds in the
      cerebellum was higher versus the other regions of the rat brain.

PMID- 10954022
TI  - The meaning of serum levels of advanced glycosylation end products in diabetic
      nephropathy.
AB  - It has been reported that advanced glycosylation end products (AGEs) play an
      important role in the development of diabetic complications. To evaluate the
      relationship between serum AGEs and diabetic nephropathy, we measured serum AGE
      levels in diabetic patients with normoalbuminuria (N), microalbuminuria (M),
      overt proteinuria (O), and hemodialysis (HD), non diabetic patients with
      nephropathy, and age-matched control subjects using the enzyme-linked
      immunosorbent assay (ELISA). Urine AGE levels were also measured in these
      subjects except group HD. Serum AGE levels in diabetic patients were not
      significantly higher than those in the normal subjects. When we compared serum
      AGE levels among various stages of diabetic nephropathy, groups O and HD had
      significantly higher serum AGE levels than the other groups. Serum AGE levels in
      group HD were almost 6-fold higher than those in groups N and M. In contrast,
      there were no significant differences in urinary AGE levels among any diabetic
      groups. As for the variables that determine serum AGE levels in diabetic
      patients, there was no significant correlation between serum AGEs and fasting
      blood glucose, hemoglobin A1c (HbA1c), or duration of diabetes. In contrast,
      serum AGEs showed a strong correlation with serum creatinine and an inverse
      correlation with creatinine clearance. To evaluate the relationship between serum
      AGEs and oxidative stress in diabetic nephropathy, urinary 8-hydroxy-2'
      deoxyguanosine (8-OHdG) and serum malondialdehyde (MDA), which are biological
      markers of total oxidative stress in vivo, were also examined. Both urinary 8
      OHdG and serum MDA levels were significantly higher in diabetic patients with
      proteinuria versus those without proteinuria. However, there was no significant
      correlation between serum AGEs and urinary 8-OHdG or serum MDA levels in diabetic
      patients. These results suggest that the accumulation of serum AGEs in diabetic
      nephropathy may be mainly due to decreased removal in the kidney rather than
      increased production by high glucose levels or oxidative stress.

PMID- 10954023
TI  - Sympathoadrenal responses to submaximal exercise in women after acclimatization
      to 4,300 meters.
AB  - The purpose of this investigation was to determine the sympathoadrenal response
      to exercise in women after acclimatization to high altitude. Sixteen eumenorrheic
      women (age, 23.6 +/- 1.2 years; weight, 56.2 +/- 4.3 kg) were studied at sea
      level and after 10 days of high-altitude exposure (4,300 m) in either the
      follicular (n = 11) or luteal (n = 5) phase. Subjects performed two 45-minute
      submaximal steady-state exercise tests (50% and 65% peak O2 consumption [VO2
      peak]) at sea level on a bicycle ergometer. Exercise tests were also performed on
      day 10 of altitude exposure (50% VO2 peak at sea level). As compared with rest,
      plasma epinephrine levels increased 36% in response to exercise at 50% VO2 peak
      at sea level, with no differences found between cycle phases. This increase was
      significantly greater (increase 44%) during exercise at 65% VO2 peak. At
      altitude, the epinephrine response was identical to that found for 65% VO2 peak
      exercise at sea level (increase 44%), with no differences found between phase
      assignments. The plasma norepinephrine response differed from that for
      epinephrine such that the increase with exercise at altitude (increase 61%) was
      significantly greater compared with 65% Vo2 peak exercise at sea level (increase
      49%). Again, no phase differences were observed. It is concluded that the
      sympathoadrenal response to exercise (1) did not differ between cycle phases
      across any condition and (2) was similar to that found previously in men, and (3)
      the relative exercise intensity is the primary factor responsible for the
      epinephrine response to exercise, whereas altitude had an additive effect on the
      norepinephrine response to exercise.

PMID- 10954024
TI  - Free leptin is increased in normal pregnancy and further increased in
      preeclampsia.
AB  - We measured bound and free leptin levels in preeclamptic and matched normal
      pregnant and never-pregnant women to determine whether the free component of
      leptin is increased during pregnancy and further increased in preeclampsia. Two
      milliliters of serum was obtained from 18 normal and 18 preeclamptic patients
      matched by pre-pregnancy body mass index (BMI), and from 18 never-pregnant women
      matched by BMI with the pregnant groups. The sample was subjected to gel
      filtration using Sephadex G-100. Radioimmunoassay (RIA) was performed on all
      fractions, and the proportions of bound and free leptin were determined by
      analyzing the areas under the curve of the chromatographic profile. The total
      maternal serum leptin concentration was significantly higher in normal pregnancy
      compared with the nonpregnant state and was further increased in preeclampsia
      (33.8 +/- 4.1 v 15.2 +/- 1.8 ng/mL, P = .002, and 48.1 +/- 5.6 ng/mL, P = .02,
      respectively). Free leptin was increased in normal pregnant compared with never
      pregnant women (25.9 +/- 4.1 v 11.0 +/- 2.0 ng/mL, respectively, P = .01), while
      the increase of total leptin in preeclampsia was exclusively in the free fraction
      that was significantly higher versus the normal pregnant group (41.8 +/- 5.6
      v25.9 +/- 4.1 ng/mL, respectively, P = .01). The bound leptin fraction, by
      contrast, was significantly increased in the normal pregnant group compared with
      the preeclamptic group and the never-pregnant group (7.9 +/- 0.56 v 6.2 +/- 0.36
      and 4.1 +/- 0.36 ng/mL, respectively, P = .009 and P = <.0001). In conclusion,
      the free leptin concentration increases in normal pregnancy and is further
      increased in preeclampsia. This supports the hypothesis that biologically active
      leptin is elevated in normal pregnancy and is increased more in women with
      preeclampsia.

PMID- 10954025
TI  - Postprandial apolipoprotein B48-and B100-containing lipoproteins in type 2
      diabetes: do statins have a specific effect on triglyceride metabolism?
AB  - There is little information about the effect of an alteration of low-density
      lipoprotein (LDL) turnover on chylomicron and very-low-density lipoprotein (VLDL)
      metabolism, yet chylomicron remnant particles are thought to be particularly
      atherogenic. This study examined the effect of inhibition of cholesterol
      synthesis on postprandial lipoproteins. Eight type 2 diabetic patients were
      examined before treatment with the 3-hydroxy-3-methyl glutaryl coenzyme A
      (HMGCoA) reductase inhibitor cerivastatin, after 4 weeks on active treatment, and
      4 weeks after stopping treatment. On each occasion, blood was collected fasting
      and at 2-hour intervals for up to 8 hours after a high-fat meal. Chylomicrons and
      VLDLs were isolated by sequential ultracentrifugation. Compositional analysis was
      performed including the measurement of apolipoprotein B48 (apo B48) and apo B100
      using polyacrylamide gradient gel electrophoresis. During statin treatment, there
      was a significant reduction in the postprandial chylomicron apo B48 area under
      the curve (AUC) from 23 +/- 16 to 17 +/- 10 (P < .01) and apo B100 in the
      chylomicron fraction from 166 +/- 148 to 70 +/- 70 (P < .05). Postprandial
      cholesterol (362 +/- 193 to 74 +/- 39, P < .005), triglyceride (2,222 +/- 1,440
      to 746 +/- 329), and phospholipid (518 +/- 267 to 205 +/- 94) also decreased (P <
      .005). In the VLDL fraction, the postprandial cholesterol and triglyceride AUC
      were significantly reduced by statin (316 +/- 228 to 171 +/- 78, P < .05, and
      1,733 +/- 833 to 857 +/- 468, P < .02, respectively). Four weeks after cessation
      of treatment, the chylomicron fraction triglyceride AUC had returned to the
      pretreatment level, but postprandial chylomicron cholesterol and VLDL
      cholesterol, triglyceride, and phospholipid were significantly lower than
      baseline (P < .05). Plasma total cholesterol and LDL cholesterol were
      significantly reduced with treatment (6.2 +/- 0.5 to 4.3 +/- 1.0 mmol/L, P <
      .001, and 4.5 +/- 0.4 to 2.8 +/- 1.0 mmol/L, P < .01, respectively) and returned
      to baseline following cessation of treatment. Fasting plasma triglycerides
      decreased significantly on treatment (2.4 +/- 1.0 to 1.7 +/- 0.2 mmol/L, P < .05)
      but remained significantly lower than baseline 4 weeks later (1.8 +/- 0.3 mmol/L,
      P < .05). This study suggests major postprandial lipoprotein changes on statin
      therapy which may account, in part, for the beneficial effects of statins in the
      prevention of myocardial infarction.

PMID- 10954026
TI  - The degree of hyperinsulinemia and impaired glucose tolerance predicts plasma
      leptin concentrations in women only: a new exploratory paradigm.
AB  - Plasma leptin has been shown to correlate positively with many indices of
      obesity, as well as insulin resistance. For a given body weight, the levels are
      higher in women than in men, but the reasons for this difference are not clear.
      Insulin has been shown to stimulate leptin production by adipose tissue in vivo
      and in vitro. Previous studies have reported that leptin levels are similar in
      diabetic and nondiabetic individuals. However, these studies were not performed
      in newly diagnosed diabetics, and other variables (such as gender) could have
      confounded the results. Therefore, the goal of the present cross-sectional study
      is to examine the effect of metabolic variables (such as glucose and insulin) on
      plasma leptin concentrations in men and women separately. We measured leptin
      levels in 48 subjects (17 with newly diagnosed type 2 diabetes mellitus, 13 with
      impaired glucose tolerance [IGT], and 18 normal individuals). The 3 groups were
      well matched for gender, age, and body mass index (BMI). When adjusted for the
      BMI and gender, a statistically significant gender-related difference in mean
      plasma leptin was observed across the 3 glucose tolerance subgroups (P < .03 by
      analysis of covariance [ANCOVA]). More specifically, plasma leptin levels were,
      on average, 44% lower in women with diabetes or IGT versus normal women (P <
      .02). No such between-group difference was observed in the men. In univariate
      analysis in the same female subgroup, plasma leptin correlated positively with
      fasting insulin (rs = +.43, P < .06) and negatively with 2-hour post-75-g glucose
      load plasma glucose concentration (rs = -.54, P < .02). In a multiple regression
      model controlling for the BMI in the female subgroup, circulating insulin and
      glucose concentrations 2 hours after the 75-g glucose load were good predictors
      of fasting plasma leptin (r = +.38, P = .02 and r = -.70, P < .001,
      respectively). Leptin levels in women appear to be influenced independently and
      to an important degree by ambient plasma glucose and plasma insulin
      concentrations. These findings suggest that the synthesis of leptin by adipose
      tissue is more susceptible to in vivo regulation by insulin and glucose in women
      than in men. Plasma leptin concentrations were also lower in women with IGT or
      type 2 diabetes versus normal women, suggesting that fasting and/or postprandial
      hyperglycemia interferes with the stimulatory effect of plasma insulin on the
      synthesis of leptin by adipose tissue in women only.

PMID- 10954027
TI  - Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and
      obesity-related phenotypes in the Quebec Family Study.
AB  - The gene-gene interactions between markers in the alpha2-, beta2-, and beta3
      adrenergic receptor (ADR) genes and obesity-related phenotypes were studied in
      the Quebec Family Study (QFS) cohort. The prevalence of the Arg allele of the
      Arg16Gly polymorphism in the beta2-ADR gene was higher (49%) in males with a body
      mass index (BMI) of 35 kg/m2 or higher versus those with a BMI less than 35 kg/m2
      (33%; P = .010). The beta2-ADR gene Arg16Gly and Gln27Glu polymorphisms were
      associated with plasma total and low-density lipoprotein (LDL) cholesterol
      concentrations. In addition, the homozygotes for the 6.3-kb allele of DraI
      polymorphism in the alpha2-ADR gene had the lowest mean abdominal subcutaneous
      fat area (P = .012) and total fat area (P = .003), as well as insulin area, under
      the curve during an oral glucose tolerance test ([OGTT] P = .004). Several ADR
      gene-gene interaction effects on abdominal fat distribution and plasma lipids
      were detected. First, significant interactions between alpha2- and beta3-ADR
      genes were observed on total (P = .015) and subcutaneous (P = .004) abdominal
      fat. Second, interaction effects between alpha2- and beta2-ADR gene variants
      influenced total, high-density lipoprotein (HDL), and LDL cholesterol
      concentrations. Finally, there were interactions between markers within the beta2
      ADR gene affecting plasma triglyceride concentrations and subcutaneous abdominal
      fat. From these results, we conclude that polymorphisms in the ADR genes
      contribute to body fat and plasma lipid variability in men. Gene-gene
      interactions among the ADR genes contribute to the phenotypic variability in
      abdominal obesity and plasma lipid and lipoprotein, but not in visceral fat
      levels.

PMID- 10954028
TI  - Methionine transamination in patients with homocystinuria due to cystathionine
      beta-synthase deficiency.
AB  - To assess the ability of patients with homocystinuria due to cystathionine beta
      synthase (CBS) deficiency to perform the reactions of the methionine
      transamination pathway, the concentrations of the products of this pathway were
      measured in plasma and urine. The results clearly demonstrate that CBS-deficient
      patients develop elevations of these metabolites once a threshold near 350
      micromol/L for the concurrent plasma methionine concentration is exceeded. The
      absence of elevated methionine transamination products previously reported among
      16 CBS-deficient B6-responsive patients may now be attributed to the fact that in
      those patients the plasma methionine concentrations were below this threshold.
      The observed elevations of transamination products were similar to those observed
      among patients with isolated hypermethioninemia. Plasma homocyst(e)ine did not
      exert a consistent effect on transamination metabolites, and betaine appeared to
      effect transamination chiefly by its tendency to elevate methionine. Even during
      betaine administration, the transamination pathway does not appear to be a
      quantitatively major route for the disposal of methionine.

PMID- 10954030
TI  - The skeletal response to estrogen.

PMID- 10954029
TI  - Decreased urinary calcium loss and lower bone turnover in young oral
      contraceptive users.
AB  - The effect of ethinyl estradiol-containing oral contraceptives (OCs) on bone
      health is still not completely understood. This study was therefore performed to
      investigate the effect of OC use on biochemical parameters of calcium (Ca) and
      bone metabolism in young women. Twelve OC users ([OC+ group] age, 24.8 +/- 0.6
      years) and 19 eumenorrheic nonusers ([OC-group] age, 25.5 +/- 0.8 years) were
      studied. Three individual urine samples (fasting 2-hour and 24-hour specimen) and
      3 blood samples collected at intervals of 28 days were pooled for data
      evaluation. Energy, nutrient intake (7-day food record), the body mass index, and
      serum 25-hydroxyvitamin D levels of the 2 groups were comparable. Serum levels of
      estradiol (E2) and sex hormone-binding globulin (SHBG) in the 2 groups mirrored
      the use and nonuse of OCs. Fasting 2-hour renal Ca excretion was markedly lower
      in the OC+ group compared with the OC- group (80.2 +/- 14.7 v 185.1 +/- 18.8
      micromol/mmol creatinine [Cr], P < .001), indicating a decrease in the urinary
      loss of endogenous, bone-derived Ca. Moreover, 24-hour renal Ca excretion was
      reduced in the OC+ group (3.65 +/- 1.46 v5.03 +/- 1.90 mmol/d, respectively, P <
      .01). In addition, serum Ca levels were lower in the OC+ group versus the OC-
      group (2.19 +/- 0.07 v 2.29 +/- 0.02 mmol/L; P < .05). The OC+ group had lower
      serum levels of carboxy-terminal propeptide of type I procollagen ([PICP] a
      biomarker of bone formation) compared with the OC- group (78.3 +/- 3.6 ng/mL in
      the OC+ group v 96.9 +/- 5.5 ng/mL in the OC- group, P < .001) and lower renal
      hydroxyproline (OHPr) excretion (a biomarker of bone resorption, 8.3 +/- 1.0 v
      11.3 +/- 1.0 micromol/mmol, Cr, P < .001). In summary, OCs reduce urinary Ca loss
      and slow bone turnover in young women. The results may help to explain the OC
      effect on bone mass in young women.

PMID- 10954031
TI  - Testosterone and leptin in older African-American men: relationship to age,
      strength, function, and season.
AB  - Testosterone (T) and bioavailable testosterone (BT) levels have been shown to
      decline with aging in Caucasian males. We are unaware of any studies that have
      examined this in African-American men. Previous studies have suggested a
      relationship of T to strength and leptin levels, but no such correlation with
      measured functional tests exists. This study explores these associations in a
      cross-sectional sample of older African-Americans from the Saint Louis University
      Inner City Aging Project. The participants were 65 African-American males aged 70
      to 102 years. Measurements included T, BT, and leptin levels, isometric muscle
      strength, and relevant physical impairments. Statistical analysis included a t
      test and simple and multiple ordinary least-squares regression. Age was inversely
      related to T and BT. Of these older African-American males, 90.7% had a BT value
      less than the normal range for young males. T correlated with upper- and lower
      limb strength and functional tests. Leptin was correlated with the body mass
      index (BMI) and inversely with T, but not with BT. Circannual rhythms for T, BT,
      and leptin were present. This study demonstrates for the first time an age
      related decrease in T and BT in African-Americans and a circannual rhythm for
      leptin. T was correlated with upper- and lower-limb strength and functional
      status.

PMID- 10954032
TI  - Effect of magnesium supplementation on the fractional intestinal absorption of
      45CaCl2 in women with a low erythrocyte magnesium concentration.
AB  - The cosupplementation of magnesium with calcium has been suggested to be
      beneficial in the prevention of osteoporosis. We investigated the effect of
      magnesium supplementation on parameters of bone resorption and fractional 45Ca
      absorption. Twenty apparently healthy women with a mean age of 39.2 +/- 9.2 years
      and an erythrocyte magnesium concentration less than 1.97 mmol/L were recruited
      into a controlled magnesium supplementation trial. During weeks 1 to 4, they
      received a daily control preparation, potassium/sodium citrate malate (PSCM).
      During weeks 5 to 8, the subjects received magnesium citrate malate (MCM)
      equivalent to 250 mg magnesium per day. During the fourth and eighth weeks, blood
      was collected for measurement of the serum intact parathyroid hormone (PTH)
      concentration and serum and erythrocyte magnesium concentration. Urine was
      collected for measurement of calcium, magnesium, creatinine, and
      deoxypyridinoline excretion. On the final day of each treatment period, 5
      microCi45CaCl2 was administered orally, and the isotope was traced in the blood
      and urine over 7 hours. Urinary calcium, 45Ca, and deoxypyridinoline excretion,
      as well as serum intact PTH levels, showed no statistically significant changes
      as a result of magnesium supplementation. However, urinary magnesium excretion
      increased by 31.1% (P < .005) while fractional 45Ca absorption decreased by 23.5%
      (P < .001) as a result of magnesium supplementation. It is concluded that
      magnesium supplementation does not result in changes in bone resorption, while
      the fractional intestinal absorption of 45Ca appears to decrease.

PMID- 10954033
TI  - The role of tachykinins via NK1 receptors in progression of human gliomas.
AB  - In recent years, it has become evident that astrocytes harbor functional
      receptors to many neurotransmitters. including substance P (SP), an undecapeptide
      belonging to the tachykinin family of neuropeptides. SP is an important stimulus
      for reactive astrocytes in CNS development, infection and injury, and provides a
      link for bi-directional interactions between glial cells and neurons. In brain
      tumors, malignant glial cells originating from astrocytes, via NK1 receptors, are
      triggered by tachykinins, SP and neurokinin A (NKA), to release soluble
      mediators, in particular cytokines, and increase their proliferative rate. In
      this paper, we review the results obtained in in vitro and in vivo studies on the
      role of SP as an inducer of human glioma responses that may be relevant for tumor
      progression. In addition, the presence of SP and the expression of NK1 receptors
      in glioma explants have been examined. We discuss the possible use of selective
      NK1 receptor antagonists as a therapeutic approach to treat malignant gliomas.

PMID- 10954034
TI  - Role of vascular endothelial growth factor (VEGF) in endothelial cell protection
      against cytotoxic agents.
AB  - Autocrine expression of VEGF has been detected in endothelial cells under hypoxia
      or oxidative stress. However, the functional significance of this VEGF autocrine
      expression remains undefined. To analyze the role of autocrine VEGF in the
      endothelial response against injury, cultured bovine aorta endothelial cells
      (BAEC) were challenged with potentially cytotoxic substances with different
      chemical structure and pharmacologic properties, namely cytochalasin D (CyD),
      hydrogen peroxide (H2O2) and cyclosporine A (CsA). Our results revealed that: i.
      In particular conditions, exposure to potentially cytotoxic agents as CyD, H2O2
      or CsA results in significant BAEC cytoprotection rather than injury. ii. The
      response to the 3 agents is shifted to a cell damaging pattern in the presence of
      a specific anti VEGF monoclonal antibody (mAb). iii. CyD and H2O2 markedly
      stimulate the autocrine expression of VEGF mRNA and VEGF protein. In conclusion,
      the present study reveals a protective mechanism of endothelial cells against
      injury involving autocrine VEGF production. Moreover, the occurrence of a
      significant increase in VEGF expression accompanying this defensive mechanism is
      further disclosed.

PMID- 10954035
TI  - Expression of steroidogenic acute regulatory protein (StAR) in rat granulosa
      cells.
AB  - Steroidogenic acute regulatory protein (StAR) is a vital mitochondrial protein
      that is indispensable for the synthesis of steroids. To study the mechanisms of
      regulation of StAR in rat granulosa cells, we used granulosa cells obtained from
      diethylstilbestrol-treated immature rats. Northern blot analysis revealed two
      major transcripts of about 3.6 kb and 1.6 kb of rat StAR mRNA. Rat StAR mRNA had
      strongly increased within 2 h due to the treatment of FSH or 8-Br-cAMP in this
      culture, a parallel increase of transcripts of both sizes was observed. Compared
      to the control, StAR mRNA levels increased in a dose-dependent manner in the
      presence of increasing concentrations of FSH (1-100 ng/ ml) and 8-Br-cAMP (0.25-5
      mM). Although co-treatment of rat granulosa cells with FSH and TGF-beta did not
      change FSH-induced StAR mRNA levels, these levels in granulosa cells were
      markedly increased by pretreatment with TGF-beta before being acutely (2 h)
      stimulated with an effective dose of FSH. The stimulatory effect of TGF-beta was
      time- and concentration-dependent (1-30 ng/ml).

PMID- 10954036
TI  - CGS 34043: a non-peptidic, potent and long-acting dual inhibitor of endothelin
      converting enzyme-1 and neutral endopeptidase 24.11.
AB  - Endothelin-1 (ET- 1) is a potent vasoconstrictor. Its biosynthesis is catalyzed
      by endothelin converting enzyme (ECE). In contrast, atrial natriuretic peptide
      (ANP) is a potent vasorelaxant and diuretic, and it is mainly degraded by neutral
      endopeptidase 24.11 (NEP). Therefore, compounds that can suppress the production
      of ET-1 by inhibiting ECE while simultaneously potentiating the levels of ANP by
      inhibiting NEP may be novel agents for the treatment of cardiovascular and renal
      dysfunction. CGS 34043 is one such compound, which inhibited the activities of
      ECE-1a and NEP with IC50 values of 5.8 and 110 nM, respectively. In vivo, it
      inhibited the pressor response induced by big ET-1, the precursor of ET-1, dose
      dependently in rats, and the inhibition was sustained for at least 2 hr. In
      addition, CGS 34043 increased plasma ANP by 150% up to 4 hr after an intravenous
      dose of 10 mg/kg in conscious rats infused with ANP. However, this compound had
      no effect on the angiotensin I-induced pressor response. These results
      demonstrate that CGS 34043 is a potent and long-lasting dual inhibitor of ECE-1
      and NEP. Consequently, it may be beneficial for the treatment of diseases in
      which an overproduction of ET-1 and/or enhanced degradation of ANP plays a
      pathogenic role. The activity of CGS 34753, an orally active prodrug of CGS
      34043, is also described.

PMID- 10954037
TI  - Morphine modulation of plasmodial-antigens-induced colony-stimulating factors
      production by macrophages.
AB  - Morphine abuse is known to cause immunosuppression and enhanced host
      susceptibility to malaria. We studied the effect of morphine on the Plasmodium
      berghei total-parasite-antigens soluble in culture medium (P.b.SA)-induced
      production of colony-stimulating factors (CSFs) by mouse peritoneal macrophages,
      in vitro. Morphine exerted a concentration-dependent biphasic modulatory effect;
      at 1 x 10(-4)-1 x 10 x 10(-6) M it slightly inhibited, whereas at 1 X 10(-8)-1 x
      10(-10) M it augmented the production of CSFs. However, at 1 x 10(-12) M
      concentration the augmenting effect of morphine was significantly (p<0.05)
      diminished. Selective agonists of delta- (DPDPE) and mu- (DAGO) opioid receptors
      also respectively, inhibited and augmented the production of CSFs. The CSFs
      appear to be synthesized de novo as cycloheximide (50.0 microg/ml) completely
      inhibited their production. Naloxone ( 1 x 10(-5) M) lacked any effect on the
      inhibitory effect of morphine; however, at 1 x 10(-3) M it exerted partial
      blocking effect. Conversely, at 1 x 10(-5) M naloxone significantly (p<0.05)
      blocked the augmenting effect of morphine. These results suggest that morphine
      via opioid receptors, in a concentration-dependent biphasic manner, modulated the
      P.b.SA-induced de novo production of CSFs by macrophages, in vitro.

PMID- 10954038
TI  - Effect of cisplatin on H+ transport by H+ -ATPase and Na+/H+ exchanger in rat
      renal brush-border membrane.
AB  - The effect of the potent anticancer drug cisplatin, cis-diamminedichloroplatinum
      (II) (CDDP), on H+ -ATPase and Na+/H+ exchanger in rat renal brush-border
      membrane was examined. To measure H+ transport by vacuolar H+ -ATPase in renal
      brush-border membrane vesicles, we employed a detergent-dilution procedure, which
      can reorientate the catalytic domain of H+ -ATPase from an inward-facing
      configuration to outward-facing one. ATP-driven H+ pump activity decreased
      markedly in brush-border membrane prepared from rats two days after CDDP
      administration (5 mg/kg, i.p.). In addition, N-ethylmaleimide and bafilomycin A1
      (inhibitors of vacuolar H+ -ATPase)-sensitive ATPase activity also decreased in
      these rats. The decrease in ATP-driven H+ pump activity was observed even at day
      7 after the administration of CDDP. Suppression of ATP-driven H+ pump activity
      was also observed when brush-border membrane vesicles prepared from normal rats
      were pretreated with CDDP in vitro. In contrast with H+ -ATPase, the activity of
      Na+/H+ exchanger, which was determined by measuring acridine orange fluorescence
      quenching, was not affected by the administration of CDDP. These results provide
      new insights into CDDP-induced renal tubular dysfunctions, especially such as
      proximal tubular acidosis and proteinuria.

PMID- 10954039
TI  - Disorders in the immune responses of T- and B-cells in mice administered
      intravenous verotoxin 2.
AB  - To obtain a better insight into the pathogenesis of verotoxin-producing
      Escherichia coli (VTEC)-associated diseases, we explored the effect of verotoxin
      2 (VT2) on the immune response in mice. The distribution of lymphocyte phenotypes
      and the lymphocyte immune response were examined after intravenous administration
      of VT2 to mice. Among the peripheral lymphocytes and splenocytes of 4-week-old
      C57BL/6 mice, there was first of all a decrease in T-cells, which began 24 h
      after intravenous administration of VT2 (50 ng/kg, lethal dose). The CD4+ cell
      subpopulations of the peripheral blood and spleen were significantly decreased at
      24 h, while the B220+ splenocyte subpopulation was markedly decreased at 45 h
      after VT2 administration. In the thymus, a decrease in CD4+CD8+ cells was
      predominantly observed near death. Interestingly, in E. coli lipopolysaccharide
      (LPS)-responder mouse strains (C57BL/6 and C3H/HeN) cotreated with LPS, the
      susceptibility to VT2 was enhanced, and the increase in B220+ cells induced by
      LPS alone was suppressed. Furthermore, splenocytes from C57BL/6 mice treated with
      VT2 (50 ng/kg) 6-24 h earlier reduced LPS-induced proliferative responses to 50
      52% of that in control cells, indicating that the effect of VT2 on the
      immunoresponse seen in vivo may be negatively exerted on the proliferation of the
      cells. In addition, the number of splenocytes that produced anti-sheep red blood
      cell antibody was decreased in mice treated with VT2. These results suggest that
      VTEC infection may eliminate CD4+ and CD8+ T-cells and B-cells by affecting their
      survival and proliferative responses, leading to reduced antibody production.

PMID- 10954040
TI  - Production of tumor necrosis factor in cells of hibernating ground squirrels
      Citellus undulatus during annual cycle.
AB  - TNF production has been studied in peritoneal macrophages and splenic T cells of
      Arctic Yakutian ground squirrel (Citellus Undulatus Pallas) in hibernating and
      awake animals in winter and in prehibernating autumn as well as in active
      euthermic spring-summer animals. A high level of TNF production in macrophages of
      ground squirrel is observed over the active period and during arousals in winter.
      There are no significant season variations in TNF production in splenic T
      lymphocytes of ground squirrels. This suggests the major role of activated
      macrophages in the arousals of hibernating animals. T lymphocyte proliferation in
      ground squirrels in the active period is higher than in winter, and the most
      significant seasonal variations are found in T cell mitogenic response, which
      increases in spring-summer period. Evidence is presented that functional activity
      of macrophages of squirrel in autumn has much in common with that in winter
      rather than in spring-summer period.

PMID- 10954041
TI  - Effects of acute alcohol intoxication on pituitary-gonadal axis hormones,
      pituitary-adrenal axis hormones, beta-endorphin and prolactin in human
      adolescents of both sexes.
AB  - Teenage drinking continues to be a major problem in industrialized countries,
      where almost 35% of alcohol drinkers are under 16 years old. In the present paper
      we studied the effects of acute alcohol intoxication (AAI) on the pituitary
      gonadal (PG) axis hormones, and the possible contribution of pituitary-adrenal
      (PA) axis hormones, beta-endorphin (BEND), and prolactin (PRL) to the alcohol
      induced dysfunction of PG axis hormones. Blood samples were drawn from
      adolescents that arrived at the emergency department with evident behavioral
      symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]).
      Our results demonstrated that AAI produces in adolescents a high increase in
      plasma PRL, ACTH, and cortisol (F), and a contradictory behavior of testosterone
      (T) according to gender: plasma T was increased in females and decreased in
      males. ACTH and PRL correlated positively with F, dehydroepiandrosterone-sulphate
      (DHEAS) and T in females, which suggests that PRL and ACTH could synergistically
      stimulate adrenal androgen production. In contrast, the decrease in T and
      increase in BEND in males suggests that AAI could have an inhibitory effect on
      testicular T, perhaps mediated by BEND. The hormones studied are involved in the
      development of secondary sexual characteristics and the growth axis during
      adolescence. The deleterious effects of alcohol abuse should be made known to
      adolescents and the appropriate authorities.

PMID- 10954042
TI  - Regulation by protein kinase C of organic anion transport driven by rat organic
      anion transporter 3 (rOAT3).
AB  - The organic anion transporter 3 (rOAT3) is a multispecific OAT localized at the
      basolateral membrane of the proximal tubule. The purpose of this study was to
      elucidate the role of protein kinase C (PKC) in the regulation of organic anion
      transport driven by rOAT3 and its mechanism of action. For this purpose, we
      established and utilized cells derived from the second segment of proximal tubule
      from mice stably expressing rOAT3 (S2 rOAT3). Phorbol 12-myristate 13-acetate
      (PMA), a PKC stimulator, attenuated the cellular uptake of estrone sulfate (ES),
      a prototype organic anion for rOAT3, in a dose- and time-dependent manner. PMA
      treatment resulted in a decrease in the Vmax, but not the Km of uptake of ES in
      S2 rOAT3. Treatment of S2 rOAT3 with other PKC stimulators or diacylglycerols
      also inhibited the uptake of ES, whereas that with an inactive phorbol ester did
      not. Chelerythrine chloride, a PKC inhibitor, reversed the PMA-induced decrease
      in uptake of ES in S2 rOAT3. These results suggest that PKC activation
      downregulates rOAT3-mediated organic anion transport. This down-regulation may be
      due to the inhibition of translocation or internalization of the rOAT3 protein,
      resulting in the decrease in the Vmax of rOAT3-mediated organic anion transport.

PMID- 10954043
TI  - The mucin biosynthesis stimulated by epidermal growth factor occurs in surface
      mucus cells, but not in gland mucus cells, of rat stomach.
AB  - Although epidermal growth factor (EGF) accelerates gastric mucin biosynthesis,
      information on whether its activation is limited to the specific mucus-producing
      cells is lacking. In this paper, we investigated the effects of EGF on mucin
      biosynthesis and the expression of its receptor in distinct layers of rat gastric
      mucosa, including the possible participation of nitric oxide (NO). EGF enhanced
      the incorporation of [3H]glucosamine and [14C]threonine into the mucin in the
      full-thickness tissues of the gastric mucosa. This stimulation disappeared on the
      removal treatment of the surface mucosal layer chiefly consisting of surface
      mucus cells. The EGF-induced increase in [3H]-labeled mucin in the full-thickness
      mucosa was not suppressed by either NG-nitro-L-arginine (10(-5) M) or 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (10(-5) M). The EGF
      receptor-mRNA expression was high in the surface mucosal layer but low in the
      deep and muscle layers of the stomach. These results suggest that EGF-induced
      stimulation of mucin biosynthesis is limited to the surface mucus cells of the
      rat gastric mucosa and is independent of the NO pathway.

PMID- 10954044
TI  - Production of nitric oxide from endothelial cells by 31-amino-acid-length
      endothelin-1, a novel vasoconstrictive product by human chymase.
AB  - Human chymase selectively converts big endothelin (ET)-1 to 31-amino-acid-length
      ET-1 [ET-1(1-31)]. In this study we examined effect of ET-1(1-31) on endothelial
      function. ET-1(1-31) evoked contraction in a concentration-dependent manner at >
      10(-8) M, which was about 10 times weaker than that of conventional ET-1 [ET-1(1
      21)]. BQ485, an ETA receptor antagonist, completely abolished ET-1(1-31)-induced
      contraction, but BQ788, an ETB receptor antagonist, slightly enhanced it,
      suggesting that ET-1(1-31) relaxes artery via endothelium. On endothelial cells,
      ET-1(1-21) and ET-1(1-31) increased [Ca2+]i and produced NO, both of which were
      significantly inhibited by BQ788 and not by BQ485. These results indicate that ET
      1(1-31) increased [Ca2+]i and produced NO in endothelial cells through ETB
      receptor similarly with ET-1(1-21), although slight difference in effect on
      smooth muscle cells.

PMID- 10954045
TI  - The decrease of mitochondrial NADH dehydrogenease and drug induced apoptosis in
      doxorubicin resistant A431 cells.
AB  - Doxorubicin (DOX) resistant A10A cells derived from human squamous carcinoma A431
      cells were found to exhibit a smaller degree of apoptosis after DOX treatment as
      compared to their parent cells. Induction of reactive oxygen species (ROS)
      formation and mitochondrial depolarization by DOX were more pronounced in the
      parent cells than in the A10A cells. The fact that catalase suppressed the DOX
      effect on ROS induction, mitochondrial depolarization and apoptosis in both cell
      lines suggests an involvement of ROS in the DOX-induced apoptosis. To investigate
      the underlying mechanisms for DOX resistance in A10A cells, RT-PCR based
      differential display was used. One of the clones, which was down-regulated in the
      A10A cells, had sequence homology with part of the mitochondrial NADH
      dehydrogenase III (ND3) gene. NADH dehydrogenase plays an important role in
      generating ROS during DOX treatment. The results indicate that down-regulation of
      ND3 may at least in part contribute to the mechanism for A10A cells resistant to
      DOX-induced apoptosis.

PMID- 10954046
TI  - Lymphocyte subpopulations, cytokines and trace elements in asymptomatic atopic
      women exposed to an urban environment.
AB  - This study evaluates the immune response to exposure to an urban environment from
      30 non-atopic and 30 non-symptomatic women with history of respiratory and/or
      cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and
      interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and
      "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the
      atopic women were higher spontaneously or in the presence of PHA, respectively.
      Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated
      with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary
      trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean
      about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes.
      Urine chromium of the non-atopic subjects was significantly correlated with
      activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was
      correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+
      CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of
      "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that
      exposure to low levels of toxic agents, produced by vehicular traffic in an urban
      environment, exerts effects on immune functions of women.

PMID- 10954047
TI  - Participation of the components of L-arginine/nitric oxide/cGMP cascade by
      chemically-induced abdominal constriction in the mouse.
AB  - The purpose of this study was to investigate the role of the L-arginine/nitric
      oxide (NO)/cGMP pathway in p-benzoquinone-induced writhing model in mouse. L
      arginine, a NO precursor, displayed antinociceptive effects at the doses of 0.125
      1.0 mg/kg. When the doses of L-arginine were increased gradually to 10-100 mg/kg,
      a dose-dependent triphasic pattern of nociception-antinociception-nociception was
      obtained. The NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME) (18.7515 mg/kg), possessed antinociceptive activity. Methylene blue (MB), a
      guanylyl cyclase and/or NOS inhibitor, (5-160 mg/kg) also produced a dose
      dependent triphasic response. When L-arginine (50 mg/ kg) was combined with L
      NAME (75 mg/kg). L-arginine-induced antinociception did not change significantly.
      Cotreatment of L-arginine with 5 mg/kg MB significantly decreased MB-induced
      antinociception and reversed the nociception induced by 40 mg/kg MB to
      antinociception. It is concluded that the components of L-arginine/nitric
      oxide/cGMP cascade may participate in nociceptive processes both peripherally and
      centrally by a direct effect on nociceptors or by the involvement of other
      related pathways of nociceptive processes induced by NO.

PMID- 10954048
TI  - Cholinergic and glutamatergic activation reverses working memory failure by
      hippocampal histamine H1 receptor blockade in rats.
AB  - Intrahippocampal administration of the histamine H1 receptor antagonist
      pyrilamine (3.2-32 ug/ side) but not the histamine H2 receptor antagonist
      cimetidine (1.0-10 microg/side) increased the number of errors in the working
      memory task with a three-panel runway setup. The increase in working memory
      errors induced by intrahippocampal 32 microg/side pyrilamine was significantly
      reduced by concurrent infusion of the histamine H1 receptor agonist 2
      pyridylethylamine (3.2 and 10 microg/side). The cholinesterase inhibitor
      physostigmine ( 1.0 and 3.2 microg/side) and D-cycloserine (0.32 and 1.0
      microg/side), the partial agonist at the glycine binding site on the NMDA
      receptor/channel complex, reduced the increase in working memory errors induced
      by intrahippocampal 32 microg/side pyrilamine. These results suggest that the
      hippocampal histaminergic activity via histamine H1 receptor is necessary for
      normal working memory processes and that the septohippocampal cholinergic
      activation and positive modulation of the NMDA receptor/channel through
      activation of the glycine site can alleviate dysfunction of hippocampal histamine
      H1 receptor-mediated neurotransmission involved in working memory function.

PMID- 10954050
TI  - Dipole estimation of alpha EEG during alcohol ingestion in males genotypes for
      ALDH2.
AB  - Using a dipole tracing method based on the two-dipole model, the purpose of the
      present study was to investigate alcohol-induced changes in the alpha band of
      electroencephalogram (EEG) and its equivalent current dipoles (ECDs) in 12
      healthy male volunteers, who were genetically typed for mitochondrial aldehyde
      dehydrogenase-2 (ALDH2). The alpha power and the mean interval dipolarity, which
      represents the goodness of fit of alpha EEG with the two-dipole model, increased
      at 30 min after 0.75 ml/kg of alcohol ingestion, when breath alcohol
      concentration showed its peak. However, the location of ECDs and distribution of
      alpha EEG did not change after alcohol ingestion. These findings indicate that
      alcohol enhances alpha EEG but does not change the location of its electrical
      sources. Interestingly, the time course of alcohol-induced EEG changes differed
      significantly according to the aversive flushing reaction after its intake. From
      60 to 120 min, the non-flushing group which had homozygous ALDH2* 1 (active type)
      displayed significant increase not only in the alpha power but also in the
      interval dipolarity compared to the baseline, whereas the flushing group with
      heterozygous ALDH2*1/2*2 (inactive type) did not exhibit this significant
      increase. The difference in the time course was discussed from the viewpoint of
      the protective effect of ALDH2*2 allele against the risk for alcoholism. These
      results suggest that the dipole tracing method could provide an alternative
      neurophysiological marker for the risk for alcoholism.

PMID- 10954049
TI  - The in vitro immunomodulatory effects of sulfasalazine on human polymorphonuclear
      leukocytes, mononuclear cells, and cultured glomerular mesangial cells.
AB  - Sulfasalazine (SSA) was investigated for its effects on phagocytic activity of
      normal human polymorphonuclear neutrophils (PMN), proliferation of mononuclear
      cells (MNC) and cultured glomerular mesangial cells. At concentrations from 25 to
      100 microM, it inhibited phagocytic activity of PMN and the 3H-thymidine
      incorporation of phytohemagglutinin (PHA)-stimulated human MNC in a dose
      dependent manner. At comparable concentrations, sulfapyridine and 5
      aminosalicylic acid, two of its major metabolites, did not show similar effects.
      SSA exhibited an inhibitory effect on both mouse and rat mesangial cells but at
      rather higher concentrations (0.5 mM). Excretion of interleukin (IL)-8 by
      lipopolysaccharide (LPS)-stimulated PMN was also markedly deterred in a dose
      dependent manner but excretion of IL-8 by LPS-stimulated MNC was not interfered
      by SSA. Production of tumor necrosis factor (TNF)-alpha and IL-1beta by mouse
      mesangial cells was not blocked by SSA but production of IL-4 by these cells was
      inhibited by it (>0.1 mM). Inhibition of MNC was not due directly to cytotoxic
      effect of SSA on these cells as shown by fluorescein diacetate stain.
      Collectively, SSA inhibits phagocytosis and IL-8 excretion by PMN as well as
      mitogen-stimulated MNC reaction. On the other hand, at high concentrations, it
      inhibits glomerular mesangial cells and their IL-4 excretion but not TNF-alpha
      and IL-1beta excretion. These results can account for minimal nephrotoxic
      characteristic of SSA and suggest that it may be helpful in the treatment of
      immune-mediated glomerulonephritis.

PMID- 10954051
TI  - Changes in the expression of cardiac Na+-K+ ATPase subunits in the UM-X7.1
      cardiomyopathic hamster.
AB  - Previous studies have shown that cardiac Na+ -K+ ATPase activity in the UM-X7.1
      hamster strain is decreased at an early stage of genetic cardiomyopathy and
      remains depressed; however, the mechanism for this decrease is unknown. The
      objective of the present study was to assess whether changes in the expression of
      cardiac Na+-K+ ATPase subunits in control and UM-X7.1 cardiomyopathic hamsters
      are associated with alterations in the enzyme activity. Accordingly, we examined
      sarcolemmal Na+-K+ ATPase activity as well as protein content and mRNA levels for
      the alpha1, alpha2, alpha3 and beta1-subunit of the Na+-K+ ATPase in 250-day-old
      UM-X7.1 and age-matched, control Syrian hamsters; this age corresponds to the
      severe stage of heart failure in the UM-X7.1 hamster. Na+-K+ ATPase activity in
      UM-X7.1 hearts was decreased compared to controls (9.0 +/- 0.8 versus 5.6 +/- 0.8
      micromol Pi/mg protein/hr). Western blot analysis revealed that the protein
      content of Na+-K+ ATPase alpha1- and beta1-subunits were increased to 164 +/- 27%
      and 146 +/- 22% in UM-X7.1 hearts respectively, whereas that of the alpha2- and
      alpha3-subunits were decreased to 82 +/- 5% and 69 +/- 11% of control values. The
      results of Northern blot analysis for mRNA levels were consistent with the
      protein levels; mRNA levels for the alpha1- and beta1-subunits in UM-X7.1 hearts
      were elevated to 165 +/- 14% and 151 +/- 10%, but the alpha2-subunit was
      decreased to 60 +/- 8% of the control value. We were unable to detect mRNA for
      the alpha3-subunit in either UM-X7. 1 or control hearts. These data suggest that
      the marked depression of Na+-K+ ATPase activity in UM-X7.1 cardiomyopathic hearts
      may be due to changes in the expression of subunits for this enzyme.

PMID- 10954052
TI  - Anticonvulsive and free radical scavenging activities of vanillyl alcohol in
      ferric chloride-induced epileptic seizures in Sprague-Dawley rats.
AB  - Vanillyl alcohol (VA) is a component of Gastrodia elata Bl. (GE), which is a
      traditional Chinese herb widely used to treat convulsive disorders or dizziness.
      This study examined the role of VA in the anticonvulsive properties of GE in a
      Sprague-Dawley rat model of epilepsy. The anticonvulsive and free radical
      scavenging activities of VA were examined after intracortical injection of ferric
      chloride (100 mM, 8 microl) to induce epileptic seizures. These seizures were
      verified by behavioral observations and electroencephalographic (EEG) and
      electromyographic (EMG) recordings. Ferric chloride injection resulted in
      increased lipid peroxide levels in the ipsilateral and contralateral cerebral
      cortex, and increased luminol-chemiluminescence (CL) and lucigenin-CL counts in
      the peripheral blood. Intraperitoneal injection (i.p.) of VA (200 mg/kg or 100
      mg/kg) or phenytoin 10 mg/kg prior to ferric chloride administration
      significantly inhibited wet dog shakes (WDS) and lipid peroxide levels in the
      bilateral cerebral cortex. VA 200 mg/kg also significantly reduced luminol-CL and
      lucigenin-CL counts in the peripheral blood, but no significant effect was
      observed following administration of VA 100 mg/kg or phenytoin. These data
      indicate that VA has both anticonvulsive and suppressive effects on seizures and
      lipid peroxidation induced by ferric chloride in rats. Data from the present
      study also demonstrate that VA has free radical scavenging activities, which may
      be responsible for its anticonvulsive propertics. This finding is consistent with
      the results from previous studies that generation of superoxide radical evoked by
      injection of iron salt into rat brain plays a critical role in ferric chloride
      induced seizures. In addition, the results of the present study suggest that the
      anticonvulsive effect of GE may be attributable, at least in part, to its VA
      component.

PMID- 10954054
TI  - Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX
      resistant and P388 parental cell lines.
AB  - It has been reported that several cis-unsaturated fatty acids (c-UFAs) could
      increase doxorubicin (DOX) accumulation in cancer cells and hence elevate its
      cytotoxicity. However, some researchers showed that c-UFA pretreatment did not
      affect its cytotoxicity in special cell lines. It is possible that the different
      results occurred due to different cellular characteristics. We hypothesized that
      c-UFA treatment might modulate the activities of some antioxidant enzymes to
      affect the resistance of cells to DOX. In the present study, we examined how c
      UFA pretreatment affected DOX cytotoxicity on mouse leukemia cell line, P388, and
      its resistant subline, P388/DOX, which we found to have significantly higher
      glutathione peroxidase (GPx) activity as well as P-glycoprotein (p-gp)
      overexpression. We chose two c-UFAs, gamma-linolenic acid (GLA) (18:3n-6) and
      docosahexaenoic acid (DHA) (22:6n-3). Cytotoxicity was measured by MTT (3-(4.5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion
      assays. DOX accumulation and p-gp expression were measured by flow cytometry. The
      activities of catalase (CAT), superoxide dismutase (SOD), glutathione S
      transferase (GST), and GPx were determined for both cell lines with and without
      treatment with GLA or DHA. Significant DOX accumulation occurred in both cell
      lines with GLA or DHA pretreatment, but without any change in p-gp expression in
      either cell line. Sensitivity to DOX cytotoxicity was improved by GLA or DHA
      pretreatment in P388/DOX in which only SOD activity was significantly increased,
      but not in the parental cell line P388 in which both SOD and CAT were
      significantly increased by the pretreatment. However, combined pretreatment of
      GLA or DHA with antioxidants, pyrrolidinedithiocarbamate (PDTC) or Vitamin C,
      could sensitize not only P388/DOX but also P388 cells to DOX. We conclude that
      the effects of c-UFA pretreatment on the sensitivity of cancer cells to DOX not
      only depend on the change in drug accumulation but also the change in the levels
      of antioxidant enzyme activities, and suggest that combined administration of c
      UFAs, antioxidants, and DOX may be more effective in treating leukemia.

PMID- 10954053
TI  - Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line.
AB  - We investigated the potential role of nerve growth factor (NGF) in osteoblast
      survival in vitro. We found the expression of the mRNAs encoding NGF, brain
      derived neurotrophic factor (BDNF), and trk-b, which is the receptor molecule of
      BDNF in mouse osteoblastic MC3T3-E1 cells. NGF high-affinity receptor trk-a was
      expressed continuously in the cells as visualized by Western blotting. A
      proinflammatory cytokine mixture stimulated NGF mRNA, and NGF protein release
      from MC3T3-E1 cells. When the effect of the nuclear factor-KB inhibitor
      pyrrolidine dithiocarbamate (PDTC) and activating protein-1 inhibitor curcumin
      were examined, a dose-dependent inhibition of cytokine-activated NGF expression
      occurred in the presence of PDTC or curcumin. Further, a specific inhibitor of
      p38 mitogen activated protein kinase (MAPK), i.e., SB203580, inhibited the
      induction of NGF in cytokines-treated cells in a dose-dependent manner whereas a
      specific inhibitor of classic MAPK, PD98059 had no effect on the induction of
      NGF. Treatment of anti-NGF IgG resulted in a potent increase of DNA fragmentation
      at a dose-dependent manner. NGF but not BDNF caused a dose-dependent reduction in
      the extent of apoptotic DNA breakdown under treatment with cytokines. Under
      similar conditions, the addition of NGF resulted in a potent reduction in bax
      protein but not in Fas, or bcl-xl. These findings demonstrated that NGF in non
      neuronal osteoblastic cells may play an important role in cell survival as an
      anti-apoptotic factor.

PMID- 10954055
TI  - Pharmacological characterization of the effects of methylmercury and mercuric
      chloride on spontaneous noradrenaline release from rat hippocampal slices.
AB  - The environmental contaminants methylmercury (MeHg) and mercuric chloride (HgCl2)
      stimulated the spontaneous release of [3H]noradrenaline ([3H]NA) from hippocampal
      slices in a time- and concentration-dependent manner. Both MeHg and HgCl2 were
      similarly potent, with an EC50 of 88.4 microM and 75.9 microM, respectively. The
      releasing effects of MeHg and HgCl2 increased in the presence of desipramine,
      showing that the mechanism does not involve reversal of the transmitter
      transporter, and were completely blocked by reserpine preincubation, indicating a
      vesicular origin of [3H]NA release. The voltage-gated Na+ channel blocker
      tetrodotoxin (TTX) did not affect the response to mercury compounds. [3H]NA
      release elicited by MeHg was partially dependent on extracellular Ca2+, since it
      decreased significantly in a Ca2+-free EGTA-containing medium whereas HgCl2
      induced a release of [3H]NA independent of extracellular Ca2+. Neither Ca2+
      channels blockers, cobalt chloride (CoCl2) and (omega-conotoxin-GVIA, nor the
      Na+/Ca2+-exchanger inhibitor benzamil reduced MeHg-evoked [3H]NA release.
      Moreover, thapsigargin or caffeine, endoplasmic reticulum Ca2+-depletors, did not
      modify metal-evoked [3H]NA release, whereas ruthenium red, which inhibits the
      mitochondrial Ca2+ transport, decreased the effect of both MeHg and HgCl2. All
      these data indicate that, in hippocampal slices, mercury compounds release [3H]NA
      from the vesicular pool by a mechanism involving Ca2+ mobilization from
      mitochondrial stores.

PMID- 10954057
TI  - Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide
      induced nitric oxide synthesis and apoptosis in cultured human trophoblasts.
AB  - We investigated the effects of nafamostat mesilate, a synthetic protease
      inhibitor clinically used for patients with pancreatitis or disseminated
      intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide
      (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an
      inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts
      induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity
      induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured
      trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors
      including nafamostat mesilate may be therapeutic agents for chorioamnionitis and
      various diseases including septic shock, ischemia-reperfusion injury in brain and
      heart, graft rejection, and acute phase inflammatory diseases, in which
      overproduction of NO or peroxynitrite is involved in tissue injury.

PMID- 10954056
TI  - Hemolysate activates P21RAS in rabbit basilar artery.
AB  - Cerebral vasospasm is the major factor of mortality and morbidity in the patients
      who have an aneurysmal subarachnoid hemorrhage (SAH). Erythrocyte lysate
      (hemolysate), oxyhemoglobin (OxyHb), and bloody cerebrospinal fluid (CSF) are the
      causative agents for vasospasm. However, the signal transduction pathways for the
      action of these spasmogens are not clear. In this study, we examined the possible
      effect of these spasmogens on the p21Ras protein, an important factor in the
      signal cascade, in rabbit basilar artery. Hemolysate enhanced p21Ras
      precipitation over a 7-day period. The initial increase of p21Ras precipitation
      occurred after the tissues were incubated for 2 days with hemolysate. The peak
      effect of hemolysate, which was markedly increased compared with control (P<0.05,
      ANOVA), was observed on day 3. OxyHb and blood CSF, in contrast, failed to
      produce consistent or marked changes in p21Ras precipitation. p21Ras inhibitors
      FTPase inhibitor 1 and manumycin abolished hemolysate-induced enhancement of
      p21Ras immunoprecipitation. Genistein, a tyrosine kinase inhibitor, failed to
      reduce the effect of hemolysate on p21Ras. We concluded that hemolysate activates
      p21Ras in the rabbit basilar artery.

PMID- 10954058
TI  - Recent advances in the treatment of bipolar mania, depression, mixed states, and
      rapid cycling.
AB  - New pharmacological agents for the treatment of bipolar disorder are under
      investigation. Some of the new potential treatments attempt to target specific
      clinical conditions that constitute particular challenges in the management of
      bipolar individuals. Typical cases of mania traditionally respond well to
      lithium, but atypical cases, in particular patients with mixed episodes, tend to
      respond poorly. The pharmacological treatment of bipolar depression is
      complicated by the phenomenon of rapid cycling, which may make the clinical
      management of these patients considerably difficult. New therapeutic agents,
      including new anticonvulsants, atypical antipsychotics, and calcium channel
      blockers are currently being examined, and bring the promise of substantial
      advances in the pharmacological management of bipolar patients. Recent
      developments in this area are reviewed, with a focus on alternatives for the
      treatment of refractory mania, bipolar depression, mixed states, and rapid
      cycling patients.

PMID- 10954059
TI  - Efficacy, safety and tolerability of combined administration of lithium and
      selective serotonin reuptake inhibitors: a review of the current evidence.
      Hertfordshire Neuroscience Research Group.
AB  - Several case reports have engendered concern about the safety of coadministering
      lithium and selective serotonin reuptake inhibitor (SSRI) antidepressants and
      there are theoretical reasons to suppose that lithium and serotonergic
      antidepressants may be associated with dangerous interactions. Systematic reports
      regarding combination therapy with lithium and SSRI antidepressants were
      assimilated for the purpose of this review. Although there are many publications,
      few are directly informative as to safety and tolerability. A total of 503
      patients are considered in systematic reports and, among these, no serious or
      life-threatening adverse events can be identified. Such data as there are
      demonstrate little potential for toxic interactions between lithium and SSRIs,
      although new, non-serious, adverse events do frequently arise. The evidence for
      the efficacy of addition of lithium to SSRIs in treatment refractory depression
      is only provisional.

PMID- 10954061
TI  - Clinical correlates of akathisia in acute psychiatric inpatients.
AB  - This study identified acute and chronic akathisia in acute psychiatric inpatients
      receiving conventional antipsychotic medication, and evaluated the clinical
      characteristics, risk factors and clinical implications of the condition.
      Akathisia and other movement disorders were systematically assessed in patients
      consecutively admitted to an acute psychiatric ward over one year. Akathisia was
      diagnosed in 15 (21%) of 72 patients. Akathisia, developing as an acute condition
      in seven patients, generally presented with the subjective experience of
      dysphoria and unease without restless movements. This acute akathisia developed
      during the first few days of hospitalization and was associated with both a
      higher average dose of antipsychotic medication and a greater increase in dosage.
      In the remaining eight cases, akathisia was already present on admission, and
      thus classified as chronic. Those patients with chronic akathisia exhibited both
      subjective restlessness and the characteristic restless movements. Chronic
      akathisia was unrelated to antipsychotic dosage. The proportion of patients with
      akathisia who discontinued drug treatment was significantly higher than that for
      patients without the condition. Patients with acute akathisia tended to drop-out
      of treatment and those with the chronic form tended to have treatment withdrawn
      by the prescribing clinician. One interpretation is that the subjective distress
      of acute akathisia may be particularly difficult for patients to tolerate and
      leads them to stop medication, while patients with more chronic akathisia may
      have become more accepting of the experience. Repetitive movements of the legs
      were observed more commonly in those with chronic rather than acute akathisia,
      and may represent a way of achieving some limited respite.

PMID- 10954060
TI  - Efficacy, cardiac safety and tolerability of sertindole: a drug surveillance.
AB  - Sertindole is a novel atypical antipsychotic, which has shown efficacy in the
      treatment of positive and negative symptoms of schizophrenia in phase II and III
      studies. Furthermore, these studies have demonstrated tolerability and a
      favourable side-effect profile. In contrast to classical antipsychotics,
      sertindole was not associated with extrapyramidal symptoms (EPS). We report drug
      surveillance data in 34 comorbid and comedicated sertindole treated patients
      suffering from different psychotic disorders. The drug surveillance consisted of
      two distinct phases: inpatient treatment and outpatient follow-up. Clinical
      global impression (severity and improvement of illness), psychotic symptoms, side
      effects, and blood parameters have been carefully documented. With special
      respect to cardiac safety electrocardiograms (ECGs) have been recorded twice
      (during sertindole treatment and during treatment with an antipsychotic different
      from sertindole). Recommended ECG-parameters for assessment of the proarrhythmic
      risk of a drug have been calculated (QTc-, QTc2-interval; QT-, QTc-dispersion).
      The majority of patients (n = 29) have been treated previously with several
      typical and/or atypical antipsychotics. We observed a clinical response to
      sertindole treatment in 29 patients (85%). Both positive and negative symptoms
      improved with sertindole and no severe side-effects have been documented. EPS
      occurred at placebo level. A mean QTc-interval prolongation of 19.7 ms (4.7%) has
      been detected. None of the patients developed clinical or electrocardiographic
      evidence of cardiac dysrhythmia during sertindole treatment, or other clinical
      evidence of cardiac abnormalities. In summary, sertindole did show efficacy for
      positive and negative symptoms together with a favourable side-effect profile. No
      evidence for an increased proarrhythmic risk has been found.

PMID- 10954062
TI  - Divalproex sodium increases plasma GABA levels in healthy volunteers.
AB  - The purpose of this study was to ascertain the effects of divalproex sodium
      (DVP), an anticonvulsant and mood stabilizer, on plasma gamma-aminobutyric acid
      (GABA) levels in healthy humans. Twenty healthy volunteers with no lifetime
      history of psychiatric illness or family history in first-degree relatives were
      recruited. Each subject received DVP 1000 mg per day for 1 week. Blood samples
      for assay of plasma levels of GABA were taken from each subject before and after
      the administration of DVP. GABA concentrations were analysed using high pressure
      liquid chromatography with fluorescence detection after derivatization with o
      phthaldialdehyde. It was found that DVP administration for 1 week resulted in a
      small, but significant, increase in plasma levels of GABA. Our results suggest
      that DVP enhances GABA activity in humans. Further treatment studies of DVP on
      GABA function in patients with psychiatric disorders are needed to explore the
      significance of the enhancing effect of DVP on GABA activity.

PMID- 10954063
TI  - Symptom-specific effects of fluoxetine in post-traumatic stress disorder.
AB  - The selective serotonin reuptake inhibitors have become a first line treatment
      for post-traumatic stress disorder (PTSD). In a recent double-blind study in
      civilians, fluoxetine produced clinically and statistically significant effects
      on all general measures of PTSD. We examined the specific effects of fluoxetine
      versus placebo in the above mentioned study of PTSD clusters and individual
      symptoms. Individuals were included if they met criteria for PTSD according to
      the Structured Clinical Interview for DSM-III-R (SCID). Symptoms were assessed at
      sequential time points by the Structured Interview for PTSD (SIP), a clinician
      interview based assessment, and a self-report scale, the Davidson Trauma Scale
      (DTS). A total of 53 patients were included in the analysis. On the SIP and DTS,
      fluoxetine was found to produce statistically significant changes on all
      clusters. Significant effects for fluoxetine were noted on 10 items of the DTS,
      and 8 items of the SIP. The SIP and DTS had 6 items in common that were
      significant. Fluoxetine exerts a broad spectrum effect in reducing all the
      symptom clusters of PTSD in this sample. The symptoms of being physically upset
      at reminders of the trauma, avoiding thoughts of the trauma, having difficulty
      enjoying things, feeling distant/estranged, having a sense of foreshortened
      future, and impaired concentration, were the symptoms most responsive to the
      effects of treatment with fluoxetine on both scales.

PMID- 10954064
TI  - Low dosage of levomepromazine did not increase plasma concentrations of
      fluvoxamine.
AB  - The cytochrome enzyme P450 2D6 (CYP2D6) is thought to play a role in the human
      metabolism of fluvoxamine. Levomepromazine is a potent inhibitor of CYP2D6. We
      coadministered a low dosage of levomepromazine and fluvoxamine in 15 patients and
      found that the low dosage of levomepromazine was effective in counteracting the
      fluvoxamine-induced insomnia and did not increase plasma fluvoxamine levels.
      These results suggest that the inhibition of CYP2D6 by levomepromazine has little
      effect on fluvoxamine metabolism. Therefore, a low dosage of levomepromazine,
      used as a hypnotic agent, appears to be effective and safe when coadministered
      with fluvoxamine. Since this was a pilot study without a placebo control, a
      double-blind placebo-controlled study is needed to confirm our preliminary
      findings.

PMID- 10954065
TI  - Olanzapine appears haematologically safe in patients who developed blood
      dyscrasia on clozapine and risperidone.
AB  - We report a 2-year experience with olanzapine treatment (20 mg daily) in a 65
      year-old male patient with treatment-resistant paranoid schizophrenia, who had
      previously developed leucopenia and neutropenia first on clozapine and,
      subsequently, also on risperidone. Olanzapine seems to be safe in this patient,
      since no major decreases of haematological parameters were observed. The only
      exception was a brief decrease of leucocyte and neutrophil (but not erythrocyte
      or platelet) counts during influenza-like viral infection. However, the control
      of psychotic symptoms on olanzapine is not as good as on clozapine.

PMID- 10954066
TI  - Occurrence of mirtazapine-induced delirium in organic brain disorder.
AB  - Mirtazapine is the first of a new class of antidepressants, the noradrenergic and
      specific serotonergic antidepressants. Its antidepressant effect appears to be
      related to its dual enhancement of both noradrenergic neurotransmission and
      serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine has
      demonstrated superior tolerability to the tricyclic antidepressants, primarily on
      account of its relative absence of anticholinergic, adrenergic and serotonin
      related adverse effects. We observed mirtazapine-induced delirium in one
      organically depressed and two major depressed patients with subclinical brain
      disease. The appearance of hallucinations, psychomotoric agitation and cognitive
      changes after initiation of mirtazapine, and their prompt improvement after drug
      discontinuation, led to the impression that these were drug-induced phenomena.
      One possible hypothesis for the observed deliria is a central increase of
      norepinephrine after acute administration of mirtazapine. Subclinical brain
      disease might have favoured the occurrence of delirium in the three cases.

PMID- 10954067
TI  - Accentuated antagonism in the control of human heart rate.
AB  - Invasive animal models indicate that the accelerative effects of the sympathetic
      nervous system on heart rate are highly dependent on the background level of
      vagal activity. A noninvasive, parasympathetic chronotropic index (respiratory
      sinus arrhythmia) and a sympathetic chronotropic index (left ventricular ejection
      time) were used to evaluate autonomic control of human heart rate. A strong
      interaction, previously called accentuated antagonism, was found. Sympathetic
      heart rate effects were substantially smaller with high levels of vagal tone than
      with low vagal background activity. Furthermore, vagal effects became
      progressively stronger with increasing sympathetic background activity,
      demonstrating the predominance of parasympathetic control of human heart rate.
      This finding implies that changes in cardiac activity resulting from changes in
      sympathetic control cannot be interpreted accurately unless concurrent vagal
      activity is taken into account, as well.

PMID- 10954068
TI  - Autonomic dysfunction in Machado-Joseph disease assessed by iodine123-labeled
      metaiodobenzylguanidine myocardial scintigraphy.
AB  - Iodine123-labeled metaiodobenzylguanidine, a radioiodinated analogue of
      norepinephrine, is a tracer for evaluating sympathetic function. We used
      iodine123-labeled metaiodobenzylguanidine myocardial scintigraphy and sympathetic
      skin response to study autonomic nervous functions in 19 patients with Machado
      Joseph disease (MJD) and 20 control subjects. Planar imaging of all the
      participants was done to evaluate myocardial scintigraphy. The ratio of average
      counts in the heart to average counts in the mediastinum was calculated for both
      early and delayed images, the latter of which reflects the cardiac neural uptake
      of the tracer. Single photon emission computed tomography also was done on 12
      patients with MJD to examine regional tracer uptake to the heart. The mean ratio
      of counts in the heart to counts in the mediastinum in the delayed images was
      lower for the patients with MJD than for the control subjects (p <0.01). Abnormal
      sympathetic skin response was present in 6 patients with MJD whose mean ratio of
      counts in the heart to counts in the mediastinum was lower than that of patients
      with MJD who had normal sympathetic skin response (p <0.01). A single photon
      emission computed tomography study showed significantly lower accumulation of the
      tracer in patients with MJD than in the control subjects in the anterior lateral
      sectors predominantly innervated by sympathetic nerves but not in the inferior
      septal sectors reported to be under main innervation by parasympathetic fibers.
      These results show that MJD is accompanied by cardiac sympathetic dysfunction, as
      detected by iodine123-labeled metaiodobenzylguanidine myocardial scintigraphy,
      which appears to be correlated with sudomotor sympathetic dysfunction.

PMID- 10954069
TI  - Differential change in cardiac baroreflex sensitivity estimated by sequence and
      spectral analysis during etomidate anesthesia.
AB  - Spontaneous baroreflex sensitivity, high-frequency gain, (0.15-0.35 Hz), and mid
      frequency gain (0.07-0.14 Hz) are noninvasive measures of cardiac baroreflex
      function derived by spontaneous sequence and cross-spectral analysis. To
      demonstrate the difference between these baroreflex estimates, 14 patients
      received etomidate (0.3 mg/kg bolus and 0.9 mg/kg/h infusion), lidocaine (60 mg),
      and vecuronium (0.1 mg/kg) by intravenous injection. The authors found that
      spontaneous baroreflex sensitivity and high-frequency gain were decreased (p
      <0.05) after etomidate anesthesia, whereas mid-frequency gain was maintained.
      Spontaneous baroreflex sensitivity, high-frequency gain, and mid-frequency gain,
      although compared simultaneously, did not change in a parallel manner. In another
      5 patients, who received normal saline only, measures were unchanged. The authors
      conclude that spontaneous baroreflex sensitivity, high-frequency gain, and mid
      frequency gain are not interchangeable. Experimental results on baroreflex
      control depend on the parameter selected.

PMID- 10954070
TI  - Assessment of the primary effect of aging on heart rate variability in humans.
AB  - Beat-to-beat heart rate variability (HRV), reflecting cardiac autonomic control
      mechanisms, is known to change with age. However, the degree to which this change
      is mediated by aging per se or by physiologic changes characteristic of normative
      aging is still unclear. This study was designed to examine the association of
      aerobic fitness, body habitus or obesity, and blood pressure with age-related
      changes in HRV. Resting HRV data was recorded from 373 healthy subjects (124 men,
      249 women; age range, 16-69 y) and analyzed by coarse-graining spectral analysis
      to decompose the total spectral power into its harmonic and fractal components.
      The low- and high-frequency (LF, 0.0-0.15 Hz; HF, >0.15 Hz) harmonic components
      were calculated from the former, whereas the latter was used to calculate the
      integrated power (FR) and the spectral exponent , beta, which were, in turn, used
      to evaluate the overall complexity of HRV. Factor analysis was performed to test
      whether potentially age-related changes in the components of HRV might be
      observed secondarily through other variables affecting HRV. Significant (p <0.05)
      age-related changes in the harmonic (HF and LF) and fractal (FR and beta)
      components of HRV were generally consistent with those described in the
      literature. In addition, factor analysis showed that there was a unique common
      factor that primarily explained correlations among age, HF, and beta (p <0.05)
      without the contributions from LF, FR, aerobic fitness, body habitus or obesity,
      and blood pressure. It was concluded that, in this population-based sample, age
      related changes in HF and beta, both of which reflect vagal modulation of heart
      rate, were primarily mediated by aging per se and not by physiologic changes
      characteristic of normative aging.

PMID- 10954071
TI  - Correlates of venous catecholamine concentrations in patients with type 1
      diabetes during a cold pressor test.
AB  - In some patients with type 1 diabetes, various physiologic reactions during a
      cold pressor test (CPT) are impaired. Whether this is caused by diabetic
      autonomic neuropathy, disturbed secretion of catecholamines, or disturbed blood
      glucose control is unknown. The authors, therefore, performed CPTs in patients
      with type 1 diabetes and in control subjects. They measured blood glucose
      concentrations, insulin concentrations, cardiac autonomic reflexes, and (before
      and after the CPT) venous catecholamine concentrations and analyzed correlations
      between these variables. Twenty-two patients with type 1 diabetes (17 men, 5
      women; mean age +/- SD, 26.6 +/- 6.5 y; diabetes duration, 7.6 +/- 0.7 y;
      glycosylated hemoglobin concentration, 7.7 +/- 2.4%) and 35 control subjects with
      comparable age and gender distributions were studied. Venous catecholamines were
      measured before and at the end of a 5-minute CPT. In patients with diabetes, only
      noradrenaline concentrations increased during the CPT, whereas adrenaline
      concentrations that were already increased at rest did not change. Adrenaline
      concentrations correlated inversely with insulin concentrations. In control
      subjects, both adrenaline and noradrenaline increased significantly during the
      CPT. In both groups, the magnitude of the individual change in catecholamine
      concentrations was inversely correlated with the respective resting
      concentration. Changes in catecholamines, cardiovascular reflex tests, and blood
      glucose concentrations did not correlate with blood pressure changes. The authors
      conclude that, in patients with diabetes, resting adrenaline concentrations are
      related to insulin concentrations. Contrary to control subjects, in patients with
      diabetes, only noradrenaline increased during CPTs. In both groups, changes in
      catecholamine concentrations after the CPT were inversely related to the
      respective resting concentrations.

PMID- 10954072
TI  - Brainstem-type Lewy body disease presenting with progressive autonomic failure
      and lethargy.
AB  - The authors report an autopsy case characterized by progressive lethargy and
      autonomic failure with a distinctive pattern of occurrence of Lewy bodies.
      Autonomic dysfunction such as sleep apnea, orthostatic hypotension, dysuria, and
      hypohidrosis predominated with lethargy, whereas parkinsonism was not apparent.
      Numerous Lewy bodies were widely evident microscopically in brainstem nuclei and
      the intermediolateral cell columns of the spinal cord, as well as in the
      sympathetic ganglia, but were rare or absent in the cerebral cortex and other
      supratentorial structures. Marked neuronal loss was seen in the locus ceruleus,
      raphe nuclei, dorsal vagal nuclei, and intermediolateral cell columns, but
      neurons in the substantia nigra, other brain regions, and sympathetic ganglia
      appeared undiminished. This case represents a specific clinicopathologic form of
      Lewy body disease occurring predominantly in the brainstem, spinal cord, and
      sympathetic ganglia.

PMID- 10954073
TI  - The Holliday junction resolvase SpCCE1 prevents mitochondrial DNA aggregation in
      Schizosaccharomyces pombe.
AB  - SpCCE1 (YDC2) from Schizosaccharomyces pombe is a DNA structure-specific
      endonuclease that resolves Holliday junctions in vitro. To investigate the in
      vivo function of SpCCE1 we made an Spcce1:ura4+ insertion mutant strain. This
      strain is viable and, despite being devoid of the Holliday junction resolvase
      activity that is readily detected in fractionated extracts from wild-type cells,
      exhibits normal levels of UV sensitivity and spontaneous or UV-induced mitotic
      recombination. In accordance with the absence of a nuclear phenotype, we show by
      fluorescence microscopy that a SpCCE1-GFP fusion localises exclusively to the
      mitochondria of S. pombe. In Saccharomyces cerevisiae the homologue of SpCCE1,
      CCE1, is known to function in the mitochondria where its role appears to be to
      remove recombination junctions and thus facilitate mitochondrial DNA segregation.
      A similar function can probably be attributed to SpCCE1 in S. pombe, since the
      majority of mitochondrial DNA from the Spcce1::ura4- strain is in an aggregated
      form apparently due to extensive interlinking of DNA molecules by recombination
      junctions. Surprisingly, this marked effect on the conformation of mitochondrial
      DNA results in little or no effect on proliferation or viability of the
      Spcce1::ura4+ strain. Possible explanations are discussed.

PMID- 10954074
TI  - Pea Ty1-copia group retrotransposons: transpositional activity and use as markers
      to study genetic diversity in Pisum.
AB  - The variation in transposition history of different Ty1-copia group LTR
      retrotransposons in the species lineages of the Pisum genus has been
      investigated. A heterogeneous population of Ty1-copia elements was isolated by
      degenerate PCR and two of these (Tps12 and Tps19) were selected on the basis of
      their copy number and sequence conservation between closely related species for
      further in-depth study of their transpositional history in Pisum species. The
      insertional polymorphism of these elements and the previously characterised PDR1
      element was studied by sequence-specific amplification polymorphism (SSAP). Each
      of these elements reveals a unique transpositional history within 55 diverse
      Pisum accessions. Phylogenetic trees based on the SSAP data show that SSAP
      markers for individual elements are able to resolve different species lineages
      within the Pisum genus. Finally, the SSAP data from all of these retrotransposon
      markers were combined to reveal a detailed picture of the intra and interspecies
      relationships within Pisum.

PMID- 10954075
TI  - Identification and chromosomal localization of the monkey retrotransposon in Musa
      sp.
AB  - Retroelements are ubiquitous features of eukaryotic genomes, often accounting for
      a substantial fraction of their total DNA content. One major group of
      retroelements, which includes the gypsy and copia-like elements, is distinguished
      by the presence of long terminal repeats (LTRs). We have identified and partially
      characterized a sequence from banana (Musa acuminata cv. Grand Nain) which shows
      significant homology to gypsy-like LTR retroelements from other species. The
      element, named monkey, shows a high degree of homology to the reverse
      transcriptase, RNase H and integrase genes of retroelements from plants, fungi
      and yeast. However, several stop codons are present in the major ORF of this
      element, suggesting that this copy of monkey, if functional, is non-autonomous.
      Southern analysis indicated that monkey is present in both the A and B genomes of
      Musa, and that it is found in 200-500 copies per haploid genome in cv. Grand
      Nain. Chromosomal localization by fluorescent in-situ hybridization indicates
      that copies of monkey are concentrated in the nucleolar organizer regions and
      colocalize with rRNA genes. Other copies of monkey appear to be dispersed
      throughout the genome.

PMID- 10954076
TI  - Molecular structure of a novel gypsy-Ty3-like retrotransposon (Kabuki) and nested
      retrotransposable elements on the W chromosome of the silkworm Bombyx mori.
AB  - We previously characterized a female-specific randomly amplified polymorphic DNA
      (RAPD), designated W-Kabuki, derived from the W chromosome of the silkworm,
      Bombyx mori. To further analyze the W chromosome of B. mori, we obtained a lambda
      phage clone which contains the W-Kabuki RAPD sequence and sequenced the 18.1-kb
      DNA insert. We found that this DNA comprises a nested structure of at least seven
      elements; three retrotransposons, two retroposons, one functionally unknown
      insertion, and one Bombyx repetitive sequence. The non-LTR retrotransposon BMC1,
      the retroposon Bm1, a functionally unknown inserted DNA (FUI), and a copia-like
      LTR retrotransposon (Yokozuma) are themselves inserted into a novel gypsy-Ty3
      like LTR retrotransposon, named Kabuki. Furthermore, this Kabuki element is
      itself inserted into another copy of Bm1. The BMCI and Yokozuna elements inserted
      in the Kabuki sequence are intact. Moreover, the Kabuki element is largely
      intact. These results suggest that many retrotransposable elements have
      accumulated on the W chromosome, and these elements are expected to evolve more
      slowly than those on other chromosomes.

PMID- 10954077
TI  - The RNase PD2 gene of almond (Prunus dulcis) represents an evolutionarily
      distinct class of S-like RNase genes.
AB  - A cDNA for an S-like RNase (RNase PD2) has been isolated from a pistil cDNA
      library of Prunus dulcis cv. Ferragnes. The cDNA encodes an acidic protein of 226
      amino acid residues with a molecular weight of 25 kDa. A potential N
      glycosylation site is present at the N-terminus in RNase PD2. A signal peptide of
      23 amino acid residues and a transmembrane domain are predicted. The two active
      site histidines present in enzymes of the T2/S RNase superfamily were detected in
      RNase PD2. Its amino acid sequence shows 71.2% similarity to RNSI of Arabidopsis
      and RNase T2 of chickpea, respectively. Northern blotting and RT-PCR analyses
      indicate that PD2 is expressed predominantly in petals, pistils of open flowers
      and leaves of the almond tree. Analyses of shoots cultured in vitro suggested
      that the expression of RNase PD2 is associated with phosphate starvation.
      Southern analysis detected two sequences related to RNase PD2 in the P. dulcis
      genome. RFLP analysis showed that S-like RNase genes are polymorphic in different
      almond cultivars. The PD2 gene sequence was amplified by PCR and two introns were
      shown to interrupt the coding region. Based on sequence analysis, we have defined
      three classes of S-like RNase genes, with the PD2 RNase gene representing a
      distinct class. The significance of the structural divergence of S-like RNase
      genes is further discussed.

PMID- 10954078
TI  - Identification of a hybrid-specific expressed gene encoding novel RNA-binding
      protein in wheat seedling leaves using differential display of mRNA.
AB  - A hybrid-specific expressed cDNA fragment, designated as AG5, has been identified
      in wheat seedling leaves using differential mRNA display. AG5 contains an open
      reading frame (ORF) encoding 183 amino acid residues. Comparison with amino acid
      sequences in GenBank revealed that the AG5 protein is homologous to a group of
      Gly-rich proteins with consensus sequence-type RNA-binding domains (CS-RBD).
      Structural analysis showed that AG5 protein contains five motifs, including a
      consensus sequence-type RNA-binding domain near its N-terminus, arginine/aspartic
      acid repeats and a Gly-rich region in its center, a Cys-X2-Cys-X4-His-X4-Cys
      (CCHC) zinc finger motif in the Gly-rich region, and TrySer2ArgAsp2Arg repeats
      towards its C-terminus. Of all previously described RNA-binding proteins, only RZ
      1 from tobacco has a similar structure to the AG5 protein, but RZ-1 lacks a
      TrySer2ArgAsp2Arg repeat motif, indicating that the two proteins may belong to a
      family of closely related proteins in plants. The possible role of AG5 and its
      relation to wheat heterosis are discussed.

PMID- 10954079
TI  - Genetic analysis of the signal-sensing region of the histidine protein kinase
      VirA of Agrobacterium tumefaciens.
AB  - The membrane-bound sensor protein kinase VirA of Agrobacterium tumefaciens
      detects plant phenolic substances, which induce expression of vir genes that are
      essential for the formation of the crown gall tumor. VirA also responds to
      specific monosaccharides, which enhance vir expression. These sugars are sensed
      by the periplasmic domain of VirA that includes the region homologous to the
      chemoreceptor Trg, and the phenolics are thought to be detected by a part of the
      cytoplasmic linker domain, while the second transmembrane domain (TM2) is
      reported to be nonessential. To define regions of VirA that are essential for
      signal sensing, we introduced base-substitution and deletion mutations into
      coding regions that are conserved among the respective domains of VirA proteins
      from various Agrobacterium strains, and examined the effects of these mutations
      on vir induction and tumorigenicity. The results show that the Trg-homologous
      region in the periplasmic domain is not essential for the enhancement of vir gene
      expression by sugars. Most mutations in the TM2 domain also failed to influence
      enhancement by sugars and reduced the level of vir induction, but a mutation in
      the TM2 region adjacent to the cytoplasmic linker abolished induction of the vir
      genes. In the linker domain, sites essential for vir induction by phenolics were
      scattered over the entire region. We propose that a topological feature formed by
      the linker domain and at least part of the TM2 may be crucial for activation of a
      membrane-anchored VirA protein. Complementation analysis with two different VirA
      mutants suggested that intermolecular phosphorylation between VirA molecules
      occurs in vivo, and that two intact periplasmic regions in a VirA dimer are
      required for the enhancement of vir induction by sugars.

PMID- 10954080
TI  - Transcription of a nitrate reductase gene isolated from the symbiotic
      basidiomycete fungus Hebeloma cylindrosporum does not require induction by
      nitrate.
AB  - Ectomycorrhizal fungi contribute to the nitrogen nutrition of their host plants,
      but no information is available on the molecular control of their nitrogen
      metabolism. The cloning and pattern of transcriptional regulation of two nitrite
      reductase genes of the symbiotic basidiomycete Hebeloma cylindrosporum are
      presented. The genomic copy of one of these genes (nar1) was entirely sequenced;
      the coding region is interrupted by 12 introns. The nar1 gene, which is
      transcribed and codes for a putative 908-amino acid polypeptide complemented
      nitrate reductase-deficient mutants of H. cylindrosporum upon transformation,
      thus demonstrating that the gene is functional. The second gene (nar2), for which
      no mRNA transcripts were detected, is considered to be an ancestral, non
      functional duplication of nar1. In a 462-nt partial sequence of nar2 two introns
      were identified at positions identical to those of introns 8 and 9 of nar1,
      although their respective nucleotide sequences were highly divergent; the exon
      sequences were much more conserved. In wild-type strains, transcription of nar1
      is repressed in the presence of a high concentration of ammonium. High levels of
      transcription are observed in the presence of either very low nitrogen
      concentrations or high concentrations of nitrate or organic N sources such as
      urea, glycine or serine. This indicates that in H. cylindrosporum, in contrast to
      all nitrophilous organisms studied so far, an exogenous supply of nitrate is not
      required to induce transcription of a nitrate reductase gene. In contrast,
      repression by ammonium suggests the existence of a wide-domain regulatory gene,
      as already characterized in ascomycete species.

PMID- 10954081
TI  - Analysis of the expression of the Rhodobacter sphaeroides lexA gene.
AB  - The regulation of the Rhodobacter sphaeroides lexA gene has been analyzed using
      both gel-mobility experiments and lacZ gene fusions. PCR-mediated mutagenesis
      demonstrated that the second GAAC motif in the sequence GAACN7GAACN7GAAC located
      upstream of the R. sphaeroides lexA gene is absolutely necessary for its DNA
      damage-mediated induction. Moreover, mutagenesis of either the first or the third
      GAAC motif in this sequence reduced, but did not abolish, the inducibility of the
      R. sphaeroides lexA gene. A R. sphaeroides lexA-defective (Def) mutant has also
      been constructed by replacing the active lexA gene with an inactivated gene copy
      constructed in vitro. Crude extracts of the R. sphaeroides lexA(Def) strain are
      unable to form any protein-DNA complex when added to the wild-type lexA promoter
      of R. sphaeroides. Likewise, the R. sphaeroides lexA(Def) cells constitutively
      express the recA and lexA genes. All these data clearly indicate that the lexA
      gene product is the negative regulator of the R. sphaeroides SOS response.
      Furthermore, the morphology, growth and viability of R. sphaeroides lexA(Def)
      cultures do not show any significant change relative to those of the wild-type
      strain. Hence, R. sphaeroides is so far the only bacterial species whose
      viability is known not to be affected by the presence of a lexA(Def) mutation.

PMID- 10954082
TI  - The role of ABC transporters from Aspergillus nidulans in protection against
      cytotoxic agents and in antibiotic production.
AB  - This paper describes the characterization of atrC and atrD (ABC transporters C
      and D), two novel ABC transporter-encoding genes from the filamentous fungus
      Aspergillus nidulans, and provides evidence for the involvement of atrD in
      multidrug transport and antibiotic production. BLAST analysis of the deduced
      amino acid sequences of AtrCp and AtrDp reveals high homology to ABC transporter
      proteins of the P-glycoprotein cluster. AtrDp shows a particularly high degree of
      identity to the amino acid sequence of Afu Mdr1p, a previously characterized ABC
      transporter from the human pathogen A. fumigatus. Northern analysis demonstrates
      an increase in transcript levels of atrC and atrD in fungal germlings upon
      treatment with natural toxic compounds and xenobiotics. The atrC gene has a high
      constitutive level of expression relative to attrD, which suggests its
      involvement in a metabolic function. Single knock-out mutants for atrC and atrD
      were generated by gene replacement using pyrG from A. oryzae as a selectable
      marker. DeltatrD mutants display a hypersensitive phenotype to compounds such as
      cycloheximide, the cyclosporin derivative PSC 833, nigericin and valinomycin,
      indicating that AtrDp is involved in protection against cytotoxic compounds.
      Energy-dependent efflux of the azole-related fungicide fenarimol is inhibited by
      substrates of AtrDp (e.g. PSC 833, nigericin and valinomycin), suggesting that
      AtrDp plays a role in efflux of this fungicide. Most interestingly, (delta)atrD
      mutants display a decrease in penicillin production, measured indirectly as
      antimicrobial activity against Micrococcus luteus. These results suggest that ABC
      transporters may be involved in secretion of penicillin from fungal cells.

PMID- 10954083
TI  - Molecular characterisation of a new mutant allele of the plastid
      phosphoglucomutase in Arabidopsis, and complementation of the mutant with the
      wild-type cDNA.
AB  - Screening of transposon-associated mutants of Arabidopsis thaliana for altered
      starch metabolism resulted in the isolation of a mutant that did not accumulate
      starch in any tissue or at any developmental stage (starch-free mutant, stf1).
      Allelism tests with known mutants showed that stf1 represents a new mutant allele
      of the plastid isoform of the enzyme phosphoglucomutase (PGMp). The mutation was
      mapped to chromosome 5. An Arabidopsis EST that showed significant homology to
      the cytosolic isoform of phosphoglucomutase (PGM) from maize was able to
      complement the mutant phenotype. The Arabidopsis EST was transcribed and
      translated in vitro and the protein product was efficiently imported into
      isolated chloroplasts and processed to its mature form. The lack of starch
      biosynthesis in stf1 is accompanied by the accumulation of soluble sugars. The
      rate of CO2 assimilation measured in individual leaves was substantially
      diminished only under conditions of high CO2 and low O2. Remarkably, stf1
      exhibits an increase rather than a decrease in total leaf PGM activity,
      suggesting an induction of the cytosolic isoform(s) in the mutant. The substrate
      for PGM, glucose 6-phosphate, accumulated in stf1 during the day, resulting in 10
      fold higher content than in the wild type at the end of the photoperiod.

PMID- 10954084
TI  - Non-coordinate regulation of 5S rRNA genes and the gene encoding the 5S rRNA
      binding ribosomal protein homolog in Neurospora crassa.
AB  - In eukaryotes, the levels of ribosomal proteins are coordinately regulated under
      varying nutritional conditions and at different developmental stages. Little is
      known about how ribosomal protein levels are coupled to the levels of rRNA. The
      formation of a ribonucleoprotein particle composed of 5S rRNA and a ribosomal
      protein is an early step in ribosome assembly. To investigate how these two
      ribosomal components are regulated in Neurospora crassa, we cloned the gene
      encoding the 5S rRNA-binding ribosomal protein (crp-4) and developed a novel
      system for measuring relative 5S rRNA transcriptional rates in vivo, using a
      reporter RNA derived from the 40S precursor RNA. The reporter RNA is cleaved from
      the 5S rRNA in vivo and therefore allows us to distinguish between changes in the
      5S rRNA transcription rate and 5S rRNA stability. Using this system, we found
      that transcription of 5S rRNA is constitutive and is not coordinated with the
      levels of crp-4 mRNA or with 40S rRNA levels during a carbon upshift or a carbon
      downshift.

PMID- 10954085
TI  - Both sense and antisense RNAs are targets for the sense transgene-induced
      posttranscriptional silencing mechanism.
AB  - Two stable transgenic tobacco lines were obtained as segregants from a primary
      transformant. Plants homozygous for a T-DNA inverted repeat locus (HOlo1) showed
      posttranscriptional gene silencing (PTGS) of the neomycin phosphotransferase II
      (nptII) transgenes, whereas HOlo2 plants, homozygous for a single T-DNA insert,
      expressed the nptII genes normally. Transient expression of nptII genes newly
      introduced into leaves of both the HOlo2 and nptII-silenced HOlo1 plants was
      downregulated only in the silenced background. Different chimeric beta
      glucuronidase (gus) genes with parts of the nptII transgene inserted in sense or
      antisense orientation into the 3'-untranslated region, which encoded transcripts
      that had homology or complementarity to nptII transcripts. showed reduced
      transient expression specifically in nptII-silenced tissue. Therefore, we
      conclude that RNAs of both polarities are targets for PTGS-induced RNA
      degradation, which supports the notion that double-stranded RNA acts as an
      inducing signal for silencing.

PMID- 10954086
TI  - Distinct requirements for the AP-3 adaptor complex in pigment granule and
      synaptic vesicle biogenesis in Drosophila melanogaster.
AB  - The AP-3 adaptor protein complex has been implicated in the biogenesis of
      lysosome-related organelles, such as pigment granules/melanosomes, and synaptic
      vesicles. Here we compare the relative importance of AP-3 in the biogenesis of
      these organelles in Drosophila melanogaster. We report that the Drosophila
      pigmentation mutants orange and ruby carry genetic lesions in the sigma3 and
      beta3-adaptin subunits of the AP-3 complex, respectively. Electron microscopy
      reveals dramatic reductions in the numbers of electron-dense pigment granules in
      the eyes of these AP-3 mutants. Mutant flies also display greatly reduced levels
      of pigments housed in these granules. In contrast, electron microscopy of
      retinula cells reveals numerous synaptic vesicles in both AP-3 mutant and wild
      type flies, while behavioral assays show apparently normal locomotor ability of
      AP-3 mutant larvae. Together, these results demonstrate that Drosophila AP-3 is
      critical for the biogenesis of pigment granules, but is apparently not essential
      for formation of a major population of synaptic vesicles in vivo.

PMID- 10954087
TI  - Cloning and analysis of the replication origin and the telomeres of the large
      linear plasmid pSLA2-L in Streptomyces rochei.
AB  - The replication origin and both terminal segments were cloned from the large
      linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. The basic replicon
      consists of a 1.9-kb DNA fragment, which contains the genetic information
      required for autonomous replication in circular form. Sequence analysis revealed
      two ORFs, RepL1 and RepL2, with no similarity to any of the replication initiator
      proteins in the database. Deletion and mutational analysis showed that RepL1 is
      essential for replication and RepL2 has a subsidiary function. The origin of
      replication may be located 800 bp upstream of repL1. Sequencing of the left and
      right terminal segments revealed the presence of 12 palindromes. The sequence of
      the first 90 bp, including palindromes I-IV, shows great similarity to that of
      other Streptomyces linear chromosomes and plasmids. These results suggest that
      the internal replication origins of the linear replicons vary widely, in contrast
      to the high degree of conservation of their telomeres.

PMID- 10954088
TI  - Disruption of plastid-encoded RNA polymerase genes in tobacco: expression of only
      a distinct set of genes is not based on selective transcription of the plastid
      chromosome.
AB  - Plastids of higher plants operate with at least two distinct DNA-dependent RNA
      polymerases, which are encoded in the organelle (PEP) and in the nucleus (NEP),
      respectively. Plastid run-on assays and Northern analyses were employed to
      analyse gene expression in tobacco mutant plastids lacking the PEP genes rpoA,
      rpoB or rpoC1. Hybridisation of run-on transcripts to restriction fragments
      representing the entire tobacco plastid chromosome, as well as to selected
      plastid gene-specific probes, shows that all parts of the plastid DNA are
      transcribed in rpo-deficient plastids. In comparison to wild-type chloroplasts,
      which are characterized by preferential transcription of photosynthesis-related
      genes in the light, mutant plastids exhibit a different transcription pattern
      with less pronounced differences in the hybridisation intensities between the
      individual genes. The analysis of steady-state transcript patterns and
      transcription rates of selected genes in both types of plastids demonstrates that
      differences in transcription rates are not necessarily paralleled by
      corresponding changes in transcript levels. The accumulation of large transcripts
      in the mutant plastids indicates that processing of primary transcripts may be
      impaired in the absence of PEP. These data suggest that, contrary to the
      prevailing view, much of the regulation of NEP-driven plastid gene expression in
      the rpo-deficient mutants is not based on differential promoter usage but is
      exerted at post-transcriptional levels.

PMID- 10954089
TI  - Members of the amylovora group of Erwinia are cellulolytic and possess genes
      homologous to the type II secretion pathway.
AB  - A cellulase-producing clone was isolated from a genomic library of the Erwinia
      rhapontici (Millard) Burkholder strain NCPPB2989. The corresponding gene, named
      celA, encodes an endoglucanase (EC 3.2.1.4) with the extremely low pH optimum of
      3.4 and a temperature optimum between 40 and 50 degrees C. A single ORF of 999 nt
      was found to be responsible for the Cel activity. The corresponding protein,
      named CelA, showed 67% identity to the endoglucanase Y of E. chrysanthemi and
      51.5% identity to the endoglucanase of Cellulomonas uda, and thus belongs to the
      glycosyl hydrolase family 8. The celA gene, or its homologue, was found to be
      present in all E. rhapontici isolates analysed, in E. chrysanthemi, and in E.
      amylovora. The presence of plant cell wall-degrading enzymes in the amylovora
      group of Erwinia spp. had not previously been established. Furthermore, the DNA
      of both E. rhapontici and E. amylovora was found to exhibit homology to genes
      encoding the type II (GSP) secretion pathway, which is known to be responsible
      for extracellular targeting of cellulases and pectinases in Erwinia spp. that
      cause soft rotting, such as E. carotovora and E. chrysanthemi. Secretion of the
      CelA protein by E. rhapontici could not be verified. However, the CelA protein
      itself was found to include the information necessary for heterologous secretion
      by E. chrysanthemi.

PMID- 10954090
TI  - The salCAB operon of Azospirillum irakense, required for growth on salicin, is
      repressed by SalR, a transcriptional regulator that belongs to the Lacl/GalR
      family.
AB  - The salAB genes of Azospirillum irakense KBC1, which encode two aryl-beta
      glucosidases, are required for growth on salicin. In the 4-kb region upstream of
      the salAB genes, two additional genes, salC and salR, were identified. SalC shows
      characteristics of the outer membrane receptors in the FepA/FhuA family. The salC
      AB genes are transcribed as a polycistronic mRNA. The salR gene encodes a protein
      homologous to the LacI/GalR family of transcriptional repressors. Expression of
      the sal operon, measured by means of a salC-gusA translational fusion in A.
      irkense KBC1, requires the presence of aryl-beta-glucosides such as arbutin and
      salicin. Expression is markedly enhanced when a simple carbon source, like
      glucose, cellobiose or malate, is added to the medium. In a salR mutant,
      expression of the salC-gusA fusion does not require an aryl-beta-glucoside
      inducer. Expression of a salR-gusA fusion is constitutive. The product of arbutin
      hydrolysis (hydroquinone) partly inhibits the expression of a salC-gusA fusion in
      arbutin- or salicin-containing minimal medium. This effect is independent of
      SalR. Salicylalcohol, the hydrolysis product of salicin, also partly inhibits
      salC expression in a SalR-independent fashion, but only in salicin-containing
      minimal medium.

PMID- 10954091
TI  - Efficient transformation of the edible basidiomycete Lentinus edodes with a
      vector using a glyceraldehyde-3-phosphate dehydrogenase promoter to hygromycin B
      resistance.
AB  - To construct a vector for high-level expression of heterologous genes in Lentinus
      edodes, the L. edodes GPD promoter, which is expressed constitutively and
      strongly, was fused to a hygromycin B phosphotransferase gene (hph) derived from
      Escherichia coli as a selective marker. Using the resulting pLG-hph construct, L.
      edodes was efficiently transformed to hygromycin resistance by restriction enzyme
      mediated integration (REMI). The restriction enzyme concentrations yielding the
      maximal numbers of transformants by the REMI method were 10 U per transformation
      in the case of BglII and 25-50 U in the case of HindIII. Southern analysis of the
      transformants indicated that some 50% of plasmid integrations were REMI-mediated
      events. These results indicate that pLG is a useful vector for transformation of
      L. edodes. Deletion analysis of the GPD promoter region suggested that the
      segment between positions -442 bp and -270 bp relative to the transcription start
      point may be essential for function.

PMID- 10954092
TI  - Identification and characterization of the mre gene region of Streptomyces
      coelicolor A3(2).
AB  - During a search for new differentiation factors in Streptomyces coelicolor A3(2),
      a locus at 11 o'clock on the S. coelicolor map was identified which harbours
      several genes that show extensive similarity to cell division and differentiation
      genes from Escherichia coli and Bacillus subtilis. From the sequence data it was
      concluded that the region contains the genes mireB, mreC, mreD (murein formation
      gene cluster E), pbp83 (high-molecular-weight penicillin-binding protein) and sfr
      (member of the spoVE/ftsW/rodA family). Mre gene products are reported to be
      responsible for determining cell shape in E. coli and Bacillus. The S. coelicolor
      mreC gene was inactivated by gene disruption, resulting in mutants which showed
      significant growth retardation in comparison to the wild type. Inactivation of
      the mreB gene was incompatible with viability, and thus mreB represents a
      Streptomyces cell division gene that is essential for survival. Promoter-probe
      experiments led to the identification of an operon structure, with promoters
      located upstream of mreB, pbp83 and sfr. Detailed studies of mreB transcription
      revealed the existence of three promoters; two of them are constitutively
      transcribed, whereas the third is developmentally regulated.

PMID- 10954093
TI  - The degenerate DNA transposon Pat and repeat-induced point mutation (RIP) in
      Podospora anserina.
AB  - A degenerate DNA transposon, Pat, was identified in the genomes of various wild
      type strains of the filamentous fungus Podospora anserina. In these strains, the
      number (approximately 20-25 copies per genome) and location of Pat sequences
      appear to be conserved. Two copies of Pat, one complete and one partial, were
      cloned and characterized. The sequence of the complete element is 1856 bp long
      and contains imperfect inverted terminal repeats (ITRs) of 53 bp. The target site
      duplication comprises the sequence TA. The amino acid sequence derived from one
      reading frame of Pat shows significant homology to members of the Fot1 family of
      transposons. However, this reading frame is interrupted by numerous stop codons.
      Since no transcripts of Pat were identified in different P. anserina strains
      grown under standard conditions and under increased stress, we conclude that none
      of the copies of Pat is active in the strains analyzed, under the environmental
      conditions investigated. Comparison of the sequences of the two cloned Pat
      sequences revealed 89% (589/747 nucleotides) identity. Most of the differences
      (82%, 129/158) can be attributed to transitions preferentially at CpA:TpG and
      CpT:ApG dinucleotides. The dinucleotide ratios in Pat are similar to those in a
      Neurospora crassa transposon which was subject to repeat-induced mutation (RIP),
      but differ significantly from those found in single-copy genes of P. anserina and
      in fungal DNA transposons not modified by this mechanism. Molecular analysis of
      the progeny of a cross between the wild-type strain and a transgenic strain in
      which a nuclear gene was duplicated by transformation yielded the first clear
      evidence that a RIP-like process is active in P. anserina.

PMID- 10954094
TI  - Treatment of osteoporosis: are physicians missing an opportunity?
AB  - BACKGROUND: Medical treatment of women with established osteoporosis may decrease
      the incidence of future fractures. Postmenopausal women who have sustained a
      distal radial fracture have decreased bone-mineral density and nearly twice the
      risk of a future hip fracture. The purpose of this study was to evaluate the
      adequacy of diagnosis and treatment of osteoporosis in postmenopausal women
      following an acute fracture of the distal part of the radius. METHODS: A
      retrospective cohort study was performed with use of a claims database that
      includes more than three million patients, from thirty states, enrolled in
      multiple health plans. All women, fifty-five years of age or older, who sustained
      a distal radial fracture between July 1, 1994, and June 30, 1997, were identified
      in the database. Only patients with at least six months of continuous and
      complete medical and pharmaceutical health-care coverage from the date of the
      fracture were enrolled, to ensure that all health-care claims would be captured
      in the database. This cohort of patients was then evaluated to determine the
      proportion who had undergone either a diagnostic bone-density scan or treatment
      with any recommended medication for established osteoporosis (estrogen, a
      bisphosphonate, or calcitonin) within six months following the fracture. RESULTS:
      A search of the database identified 1,162 women, fifty-five years of age or
      older, who had a distal radial fracture. Of these 1,162 patients, thirty-three
      (2.8 percent) underwent a bone-density scan and 266 (22.9 percent) were treated
      with at least one of the medications approved for treatment of established
      osteoporosis. Twenty women had both a bone-density scan and drug treatment.
      Therefore, only 279 (24.0 percent) of the 1,162 women who sustained a distal
      radial fracture underwent either diagnostic evaluation or treatment of
      osteoporosis. There was a significant decrease in the rate of treatment of
      osteoporosis with increasing patient age at the time of the fracture (p <
      0.0001). CONCLUSIONS: Current physician practice may be inadequate for the
      diagnosis and treatment of osteoporosis in postmenopausal women who have
      sustained a distal radial fracture.

PMID- 10954095
TI  - Histological analysis of human meniscal allografts. A preliminary report.
AB  - BACKGROUND: Little is known about the biology of meniscal allograft
      transplantation in humans. In particular, little information is available about
      the phenotype of the cells that repopulate the allograft, whether an immune
      response is elicited against the graft, and whether the repopulating cells
      synthesize normal extracellular matrix components. METHODS: A small biopsy
      specimen of the meniscal allograft (twenty-eight menisci in twenty-five patients)
      and the adjacent synovial membrane (sixteen patients) was harvested during follow
      up arthroscopy in patients who had undergone meniscal allograft transplantation
      at a mean of sixteen months earlier. Seventeen patients had undergone concomitant
      reconstruction of the anterior cruciate ligament with an allograft. Normal
      menisci (unimplanted allografts) and synovial specimens from age-matched controls
      were examined as well. All twenty-eight meniscal allografts were examined
      histologically. Immunohistochemical analysis was carried out on ten menisci and
      nine synovial specimens with use of monoclonal antibodies to class-I and class-II
      major histocompatibility complex antigens, CD-8, CD-11b, and CD-19 epitopes, as
      well as other epitopes, to demonstrate immunogenic macromolecules, cytotoxic T
      lymphocytes, activated macrophages, and B-lymphocytes. RESULTS: Most of the
      specimens demonstrated incomplete repopulation with viable cells. The
      repopulating cells stained positively with phenotype markers for both synovial
      cells and fibroblasts. Polarized light microscopy demonstrated evidence of active
      remodeling of the matrix. The cells in frozen, unimplanted menisci stained
      positively for class-I and class-II human leukocyte antigens, indicating
      immunogenicity at the time of transplantation. Overall, nine of twelve specimens
      contained immunoreactive cells (B-lymphocytes or cytotoxic T-cells) in the
      meniscus or synovial tissue. However, only a small number of these cells was
      present. There was no evidence of frank immunological rejection. The clinical
      outcome (success or failure of the transplant) was not related to the overall
      histological score or to the presence of an immune response in the meniscal or
      synovial biopsy specimen. CONCLUSIONS: Human meniscal allograft transplants are
      repopulated with cells that appear to be derived from the synovial membrane;
      these cells appear to actively remodel the matrix. Although there is histological
      evidence of an immune response directed against the transplant, this response
      does not appear to affect the clinical outcome. The presence of
      histocompatibility antigens on the meniscal surface at the time of
      transplantation (even after freezing) indicates the potential for an immune
      response against the transplant. CLINICAL RELEVANCE: Despite the absence of frank
      immunological rejection, a subtle immune reaction may affect the healing,
      incorporation, and revascularization of the graft. It is possible that the
      structural remodeling associated with cellular repopulation may render the
      meniscus more susceptible to injury.

PMID- 10954096
TI  - Parosteal osteosarcoma of the posterior aspect of the distal part of the femur.
      Oncological and functional results following a new resection technique.
AB  - BACKGROUND: Parosteal osteosarcoma is a low-grade malignant bone tumor that
      arises from the surface of the metaphysis of long bones. Parosteal osteosarcoma
      is usually well differentiated and displays a low propensity to metastasize. Wide
      resection of a parosteal osteosarcoma has been shown to provide a relatively risk
      free method of preventing local recurrence. We propose a new method of resection
      of parosteal osteosarcomas located in the popliteal paraosseous space of the
      distal part of the femur. This method involves resection of the mass through
      separate medial and lateral incisions, which allows for wide margins yet limits
      the amount of dissection of the soft tissues and the neurovascular bundle.
      METHODS: Six patients with parosteal osteosarcoma located on the posterior aspect
      of the distal part of the femur underwent resection of the lesion and
      reconstruction with a posterior hemicortical allograft through dual medial and
      lateral incisions. The patients were evaluated with regard to pain, postoperative
      function, union of the allograft (osteosynthesis), and the prevalence of local
      recurrence. RESULTS: The average time until the last follow-up assessment was 4.3
      years. No metastases developed, and there were no local recurrences. All patients
      were free of disease at the last follow-up evaluation. Postoperatively, the
      average range of motion of the knee was 0 to 122 degrees. Five of the six
      patients were free of pain at the time of the latest follow-up. Five of the six
      patients returned to their preoperative active functional status. CONCLUSIONS: We
      recommend resection of a parosteal osteosarcoma located on the posterior surface
      of the femur through separate medial and lateral incisions. This approach
      provides minimal dissection of the neurovascular bundle but ample exposure for
      reconstruction with a hemicortical allograft.

PMID- 10954097
TI  - Correlations with patients' perspectives of the result of lower-extremity
      amputation.
AB  - BACKGROUND: Patients' perceptions of the result of lower-extremity amputation
      vary widely, yet the factors associated with this variability are not well
      understood. Our objective was to identify important correlations with the
      perceived result that may help to indicate the factors that deserve particular
      emphasis in the management of patients who have had an amputation. METHODS: In
      this retrospective study, 148 patients who had had a major lower-extremity
      amputation completed a standardized questionnaire designed to assess the
      demographic characteristics, comorbidities, amputation characteristics,
      prosthetic function, and social function at a mean of seven years after surgery.
      We correlated each of these variables with four result metrics: general
      satisfaction, quality of life, freedom from frustration, and walking distance.
      RESULTS: The four result metrics were significantly and strongly correlated with
      (1) the comfort of the residual limb; (2) the condition of the contralateral
      limb; (3) the comfort, function, and appearance of the prosthesis; (4) social
      factors; and (5) the ability to exercise recreationally (p < 0.0001).
      Interestingly, the level and laterality of the amputation were not significantly
      correlated with the patients' perceived result. CONCLUSIONS: The perceived result
      of amputation is not associated with the amount of the limb that was amputated
      but rather with factors that may be optimized by surgical, prosthetic, and social
      management.

PMID- 10954098
TI  - The consequences of anterior femoral notching in total knee arthroplasty. A
      biomechanical study.
AB  - BACKGROUND: Notching of the anterior femoral cortex during total knee
      arthroplasty has been implicated as a cause of subsequent periprosthetic
      supracondylar femoral fracture. However, other than observational clinical data,
      no reliable association between these events has been established, to our
      knowledge. The purpose of the present study was to investigate the biomechanical
      effects of notching of the anterior femoral cortex. METHODS: The femoral
      component of a total knee replacement was implanted in twelve matched pairs of
      human cadaveric femora; one specimen in each pair had preservation of the
      anterior femoral cortex, and the other had a full-thickness cortical defect
      created just proximal to the anterior flange of the femoral component. The pairs
      were then subjected to either bending or torsional loading to failure. Both the
      fracture pattern and the quantitative load to failure were analyzed. Two matched
      pairs were excluded from the analysis because of inadvertent fracture during
      placement of the component. RESULTS: Following the application of a bending load,
      femora with notching of the anterior femoral cortex sustained a short oblique
      fracture that originated at the cortical defect proximal to the femoral component
      and femora without notching had a midshaft fracture. In contrast, notching of the
      anterior femoral cortex had no effect on the fracture pattern that was observed
      after the application of a torsional load. The mean load to failure was
      significantly reduced by notching in both testing modes. Notching decreased
      bending strength from 11,813 to 9690 newtons (18 percent; p = 0.0034), and it
      decreased torsional strength from 134.7 to 81.8 newton-meters (39.2 percent; p =
      0.01). CONCLUSIONS: Biomechanical testing demonstrated that notching of the
      anterior femoral cortex significantly lessens the load to failure following total
      knee arthroplasty and influences the subsequent fracture pattern. These effects
      are manifested in different ways under the two loading conditions: the fracture
      pattern is altered under bending load, and there is a greater quantitative
      decrease in load to failure with torsional loading. CLINICAL RELEVANCE: Weakening
      of the femur by notching of the anterior cortex after total knee arthroplasty may
      warrant alteration in the customary postoperative regimen for these patients.
      Manipulation of a total knee replacement with a notched anterior femoral cortex
      should probably be avoided.

PMID- 10954099
TI  - Characterization of long-term femoral-head-penetration rates. Association with
      and prediction of osteolysis.
AB  - BACKGROUND: We examined the relationship between long-term femoral-head
      penetration patterns and osteolysis in a ten-year follow-up study of a well
      controlled patient population. The purposes of this study were to characterize
      the linearity of long-term head-penetration patterns over time, to describe the
      relationship between ten-year true wear rates and osteolysis, and to determine
      whether the occurrence of osteolysis at ten years could be predicted by
      penetration data obtained prior to five years. METHODS: Temporal femoral-head
      penetration patterns were examined at a minimum of ten years after forty-eight
      primary total hip arthroplasties. The arthroplasties were performed with the use
      of an Arthropor acetabular cup (Joint Medical Products) and a thirty-two
      millimeter-diameter cobalt-chromium femoral head (DePuy). Using a computer
      assisted radiographic technique, we evaluated two-dimensional head penetration on
      serial annual radiographs. Linear regression analysis modeled penetration-versus
      time data as a line for each patient. The slope of the regression line indicated
      the true wear rate for each patient. In a subgroup of thirty-four hips for which
      three annual radiographs had been made less than five years after the
      arthroplasty, we compared early head-penetration patterns with the later
      occurrence of osteolysis. RESULTS: For all forty-eight hips, the true wear rate
      averaged 0.18 millimeter per year (range, 0.01 to 0.44 millimeter per year) and
      temporal head-penetration patterns tended to be linear (mean r2 = 0.91 +/- 0.16).
      Osteolysis at ten years was strongly associated with increasing true wear rates
      (p < 0.001). Osteolysis did not develop in any of the nine hips with a true wear
      rate of less than 0.1 millimeter per year. However, osteolysis developed in nine
      (43 percent) of twenty-one hips with a rate between 0.1 and less than 0.2
      millimeter per year, in eight of ten hips with a rate between 0.2 and 0.3
      millimeter per year, and in all eight hips with a rate of greater than 0.3
      millimeter per year. Evaluation of early true wear rates as a predictor of late
      osteolysis showed a similar relationship. CONCLUSIONS: This study demonstrates
      that true wear rates tend to be constant and that increased true wear is
      significantly associated with osteolysis at ten years after the operation. A
      similar relationship was also found at the early follow-up interval, indicating
      that early true wear rates (determined from serial radiographs) might enable
      orthopaedists to predict if patients are at risk for the development of
      osteolysis. CLINICAL RELEVANCE: On the basis of these findings, we use temporal
      femoral-head-penetration data in our practice to evaluate polyethylene inserts in
      asymptomatic patients, to estimate the time to component wear-through, and to
      adjust the frequency of follow-up evaluations for monitoring the development of
      osteolytic lesions in at-risk patients.

PMID- 10954100
TI  - Comparison of arthroscopic and open anterior shoulder stabilization. A two to six
      year follow-up study.
AB  - BACKGROUND: Sixty-three consecutive patients with recurrent traumatic anterior
      shoulder instability underwent operative repair. The decision to select either
      arthroscopic Bankart repair or open capsular shift was based on the findings of
      an examination under anesthesia and the findings at the time of arthroscopy.
      Thirty-nine patients with only anterior translation on examination under
      anesthesia and a discrete Bankart lesion underwent arthroscopic Bankart repair
      with use of absorbable transfixing implants. Twenty-four patients with inferior
      translation in addition to anterior translation on examination under anesthesia
      and capsular laxity or injury on arthroscopy underwent an open capsular shift.
      METHODS: Treatment outcomes for each group were determined according to the
      scoring systems of Rowe et al., the American Shoulder and Elbow Surgeons, and the
      Short Form-36. Failure was defined as recurrence of dislocation or subluxation or
      the finding of apprehension. Fifty-nine (94 percent) of the sixty-three patients
      were examined and filled out a questionnaire at a mean of fifty-four months
      (range, twenty-seven to seventy-two months) following surgery. RESULTS: There
      were no significant differences between the two groups with regard to the
      prevalence of failure or any of the other measured parameters of outcome. An
      unsatisfactory outcome occurred after nine (24 percent) of thirty-seven
      arthroscopic repairs and after four (18 percent) of twenty-two open
      reconstructions. All cases of recurrent instability resulted from a reinjury in a
      contact sport or a fall less than two years postoperatively. The treatment groups
      did not differ with regard to patient age, hand dominance, mechanism of initial
      injury, duration of follow-up, or delay until surgery. Measured losses of motion
      were minimal and, with the exception of forward elevation, slightly more of which
      was lost after the open capsular shifts (p = 0.05), did not differ between the
      two forms of treatment. Approximately 75 percent of the patients in each group
      returned to their favorite recreational sports with no or mild limitations. As
      rated by the patients, the result was good or excellent after thirty-one (84
      percent) of the arthroscopic procedures and after twenty (91 percent) of the open
      procedures. CONCLUSIONS: Arthroscopic and open repair techniques for the
      treatment of recurrent traumatic shoulder instability yield comparable results if
      the procedure is selected on the basis of the pathological findings at the time
      of surgery.

PMID- 10954101
TI  - Management of chronic deep infection following rotator cuff repair.
AB  - BACKGROUND: Deep infection of the shoulder following rotator cuff repair is
      uncommon. There are few reports in the literature regarding the management of
      such infections. METHODS: We retrospectively reviewed the charts of thirteen
      patients and recorded the demographic data, clinical and laboratory findings,
      risk factors, bacteriological findings, and results of surgical management.
      RESULTS: The average age of the patients was 63.7 years. The interval between the
      rotator cuff repair and the referral because of infection averaged 9.7 months. An
      average of 2.4 procedures were performed prior to referral because of infection,
      and an average of 2.1 procedures were performed at our institution. All patients
      had pain on presentation, and most had a restricted range of motion. Most
      patients were afebrile and did not have an elevated white blood-cell count but
      did have an elevated erythrocyte sedimentation rate. The most common organisms
      were Staphylococcus epidermidis, Staphylococcus aureus, and Propionibacterium
      species. At an average of 3.1 years, all patients were free of infection. Using
      the Simple Shoulder Test, eight patients stated that the shoulder was comfortable
      with the arm at rest by the side, they could sleep comfortably, and they were
      able to perform activities below shoulder level. However, most patients had poor
      overhead function. CONCLUSIONS: Extensive soft-tissue loss or destruction is
      associated with a worse prognosis. Extensive debridement, often combined with a
      muscle transfer, and administration of the appropriate antibiotics controlled the
      infection, although most patients were left with a substantial deficit in
      overhead function of the shoulder.

PMID- 10954102
TI  - Current trends in the management of adamantinoma of long bones. An international
      study.
AB  - BACKGROUND: Adamantinoma of long bones is a rare tumor. Published reviews of the
      orthopaedic management of adamantinoma have involved limited follow-up of small
      numbers of patients. The oncological aggressiveness of this tumor is unknown.
      Limb salvage is currently the treatment of choice for most adamantinomas. The
      purpose of this study was to evaluate the characteristics of adamantinoma of long
      bones as well as the oncological outcome and the complications of limb salvage
      operations. METHODS: A retrospective study was designed to evaluate the clinical
      outcomes of limb salvage operations for the treatment of adamantinoma. Data on
      seventy biopsy-proven cases of adamantinoma treated between 1982 and 1992 at
      twenty-three different cancer centers in Europe and North America were obtained.
      RESULTS: The median duration of follow-up was 7.0 years. The male:female ratio
      was 3:2, and the mean age was thirty-one years. Limb salvage was attempted in 91
      percent (sixty-four) of the seventy patients, and the final rate of limb
      preservation was 84 percent (fifty-nine of seventy). Wide operative margins were
      obtained in 92 percent (fifty-eight) of sixty-three patients. An intercalary
      allograft was used to reconstruct the segmental bone defect in 51 percent (thirty
      six) of the seventy patients. Reconstruction-related complications occurred in 48
      percent (thirty) of sixty-two patients. Nonunion and fracture were the most
      common complications, occurring in 24 percent (fifteen) and 23 percent (fourteen)
      of sixty-two patients, respectively. Kaplan-Meier analysis demonstrated a rate of
      local recurrence of 18.6 percent at ten years. Wide operative margins were
      associated with a lower rate of local recurrence than marginal or intralesional
      margins were (p < 0.00005). Kaplan-Meier analysis showed a survival rate of 87.2
      percent at ten years. There were no significant relationships between survival
      and the stage of the tumor (p = 0.058), duration of symptoms (p = 0.90), gender
      (p = 0.79), or wide operative margins (p = 0.14). CONCLUSIONS: Current treatment
      of adamantinoma, including en bloc tumor resection with wide operative margins
      and limb salvage, provides lower rates of local recurrence than has been
      previously reported. In the present study, the limb preservation rate was 84
      percent (fifty-nine of seventy), and the survival rate was 87.2 percent at ten
      years. The rate of complications related to the limb reconstruction was high.

PMID- 10954103
TI  - Bipolar hip arthroplasty as a salvage treatment for instability of the hip.
AB  - BACKGROUND: Recurrent instability of the hip in the absence of an identifiable
      cause is a challenging problem. It has been proposed that bipolar hip
      arthroplasty may have a role in the treatment of these complex cases. The purpose
      of our study was to evaluate the results of bipolar hip arthroplasty for the
      treatment of recurrent instability of the hip in a series of patients at our
      institution. METHODS: We reviewed the records of twenty-seven patients who had
      undergone bipolar hip arthroplasty as a salvage procedure for the treatment of
      recurrent instability of the hip after total hip replacement. All patients had
      undergone at least two, and a mean of three, stabilizing operative procedures on
      the hip prior to the bipolar arthroplasty. The mean duration of follow-up was
      five years (range, two to twelve years), with no patient lost to follow-up. There
      were six deaths, of unrelated causes. RESULTS: Bipolar arthroplasty prevented
      redislocation in twenty-two hips (81 percent). At the time of final follow-up,
      twenty-five patients (93 percent) had a stable hip. Five patients (19 percent)
      had had episodes of subluxation or dislocation following the bipolar
      arthroplasty. Two of these patients had only a single episode of dislocation that
      was treated successfully by immobilization. Two of the remaining three patients
      required a reoperation because of the instability. The hip was stabilized with
      the use of a constrained cup prosthesis in one of these patients, and the other
      patient eventually required resection arthroplasty. The third patient had
      continuing instability but improved function and pain relief, and a reoperation
      was not performed. There were a total of seven reoperations; these included
      revision because of disassembly of the cup in one hip, revision bipolar
      arthroplasty because of continuing instability in two, resection arthroplasty
      because of deep infection in two, revision arthroplasty because of recalcitrant
      groin pain in one, and revision arthroplasty because of deep infection and
      superior migration of the implant in one. The Harris hip score improved
      significantly, from a mean of 24 points (range, 5 to 45 points) preoperatively to
      a mean of 55 points (range, 35 to 80 points) postoperatively (p < 0.05).
      CONCLUSIONS: We believe that, despite some potential problems, bipolar hip
      arthroplasty can have a role in the salvage management of recurrent instability
      of the hip in patients in whom other stabilization procedures have failed.

PMID- 10954104
TI  - Chondroblastoma of bone.
AB  - BACKGROUND: Chondroblastoma of bone is a rare lesion, and few large series have
      been reported. The purpose of this paper is to report forty-seven cases treated
      by one group of surgeons and to identify factors associated with more aggressive
      tumor behavior. METHODS: Seventy-three patients with chondroblastoma of bone were
      treated between 1977 and 1998. We were able to obtain historical data, imaging
      studies, histological findings, and adequate personal or telephone follow-up to
      determine the outcome for forty-seven patients. RESULTS: The lesions were
      distributed widely in the skeleton, but most were in the epiphyses or apophyses
      of the long bones, especially the proximal part of the tibia (eleven tumors) and
      the proximal part of the humerus (ten tumors). The principal presenting symptoms
      were pain and limitation of movement. The treatment consisted of a variety of
      procedures, but the majority of the patients had intralesional curettage and
      packing with allograft or autograft bone chips or polymethylmethacrylate. Most of
      the patients had an excellent functional result, although in three osteoarthritis
      developed in the adjacent joint. Seven patients (15 percent) had a local
      recurrence; three of them had a second recurrence and one, a third recurrence.
      One patient died of widespread metastases, and another who had metastases to
      multiple sites was alive and disease-free after aggressive treatment of the
      metastatic lesions. CONCLUSIONS: While the size of the lesion, the age and gender
      of the patient, the status of the growth plate, and an aneurysmal-bone-cyst
      component to the tumor had no significant effect on the recurrence rate, lesions
      around the hip (the proximal part of the femur, the greater trochanter, and the
      pelvis) accounted for the majority (five) of the seven recurrent tumors and one
      of the two metastatic lesions.

PMID- 10954105
TI  - Acetabular revision after failed total hip arthroplasty in patients with
      congenital hip dislocation and dysplasia. Results after a mean of 8.6 years.
AB  - BACKGROUND: Revision of a total hip arthroplasty in a patient who has had
      congenital hip dysplasia or dislocation is often more difficult than a standard
      revision operation. The purpose of this study was to assess the efficacy and
      complications of use of a cementless hemispherical acetabular component for
      revision of an acetabular component of a failed total hip replacement in patients
      whose initial problem was arthritis secondary to congenital dislocation or
      dysplasia. The mean duration of follow-up was approximately eight years. METHODS:
      We reviewed a consecutive series of sixty-one hips in fifty-three patients who
      underwent a cementless acetabular revision with use of a hemispherical acetabular
      component, with or without concurrent femoral revision. Data were collected
      prospectively. The mean age of the patients at the time of the index operation
      was fifty-six years. A mean of 1.9 ipsilateral hip operations had been performed
      previously. Thirty-nine hips (64 percent) had a so-called high hip center prior
      to the index revision. With one exception, the uncemented acetabular component
      was fixed with screws. Fifty-one acetabular components were placed with so-called
      line-to-line fit, and ten were oversized by one to three millimeters. In thirty
      eight hips, the femoral component was revised as well. Twenty-nine femora were
      reconstructed with use of a cemented device, and nine were revised with an
      uncemented patch-porous-coated femoral stem (a stem on which the porous coating
      appears in patches). RESULTS: Four patients (five hips) died prior to the five
      year minimum follow-up interval. With the exception of one hip treated with
      resection arthroplasty because of deep infection, none of the hips in these
      deceased patients had been revised or had a loose component. One living patient
      (one hip) had a resection arthroplasty, and one additional patient (two hips) had
      both stable acetabular components rerevised at the time of femoral rerevision at
      another institution because of loosening and osteolysis. One patient refused to
      return for follow-up, but the components had not been revised. The remaining
      fifty-two hips in forty-six patients were followed for a mean of 8.6 years
      (range, 5.0 to 12.7 years). The mean Harris hip score was 80 points (range, 56 to
      100 points) at the time of the latest follow-up. No acetabular component had been
      revised, although two had migrated. No other acetabular component was loose
      according to our radiographic criteria. Thus, the mechanical failure rate on the
      acetabular side was 3 percent (two of sixty-one) for the entire series and 4
      percent (two of fifty-two) for the patients who had been followed for a mean of
      8.6 years. On the femoral side, the mechanical failure rate was 3 percent (one of
      twenty-nine) for the cemented stems and six of nine for the uncemented patch
      porous-coated stems. CONCLUSIONS: Of the approaches used in this difficult series
      of patients requiring revision, the hybrid arthroplasty (a cementless acetabular
      component and a cemented femoral component) yielded overall good results after an
      intermediate duration of follow-up.

PMID- 10954106
TI  - Odontoid fracture associated with a pharyngeal tear. A case report.

PMID- 10954107
TI  - Etiology of idiopathic scoliosis: current trends in research.
AB  - Current population studies characterize idiopathic scoliosis as a single-gene
      disorder that follows the patterns of mendelian genetics, including variable
      penetrance and heterogeneity. The role of melatonin and calmodulin in the
      development of idiopathic scoliosis is likely secondary, with indirect effects on
      growth mechanisms. Reported abnormalities of connective tissue, skeletal muscle,
      platelets, the spinal column, and the rib cage are all thought to be secondary to
      the deformity itself. Although no consistent neurological abnormalities have been
      identified in patients with idiopathic scoliosis, it is possible that a defect in
      processing by the central nervous system affects the growing spine. The true
      etiology of idiopathic scoliosis remains unknown; however, it appears to be
      multifactorial.

PMID- 10954109
TI  - Imaging of scaphoid fractures.

PMID- 10954108
TI  - Professionalism and medicine's social contract.

PMID- 10954110
TI  - Distraction osteogenesis for tibial lengthening.

PMID- 10954111
TI  - Aseptic loosening of an uncemented acetabular cup.

PMID- 10954112
TI  - Achilles tenotomy in diabetics.

PMID- 10954113
TI  - Thromboembolic prophylaxis.

PMID- 10954114
TI  - Pinealectomy and scoliosis.

PMID- 10954115
TI  - Calcaneal fractures.

PMID- 10954116
TI  - Patient-reported measure of knee function.

PMID- 10954117
TI  - Reconstruction of the anterior cruciate ligament.

PMID- 10954118
TI  - Chondrosarcoma of bone.

PMID- 10954119
TI  - Physeal arrest.

PMID- 10954120
TI  - World Federation of Hemophilia.

PMID- 10954121
TI  - Survivorship of total ankle arthroplasty.

PMID- 10954122
TI  - Intracompartmental pressure thresholds.

PMID- 10954123
TI  - Periarticular ossification.

PMID- 10954124
TI  - Facilitation of calcium influx by propylene glycol through the voltage-dependent
      calcium channels in PC12 cells.
AB  - Propylene glycol (PG) raises an intracellular calcium concentration ([Ca2+]i) in
      PC12 cells. The present study has been undertaken to examine whether or not the
      voltage-dependent Ca2+ channels are involved in the PG-induced rise in [Ca2+]i
      and, if so, to determine which types participate in it. CdCl2 (50 micro M) and
      the Ca2+ -free saline depressed the action of PG (0.5 - 10 %v/v)-induced [Ca2+]i
      rise. Although NiCl2 (50 micro M) at the same concentration as CdCl2, and omega
      agatoxin (50 and 300 nM) had no effect on the PG-induced [Ca2+]i rise, each of
      omega-conotoxin (1 micro M), nifedipine (10 micro M), nicardipine (10 micro M),
      varapamil (10 micro M) and diltiazem (10 micro M) significantly decreased it.
      Electrical stimulation and Bay K 8644 (1 micro M) enhanced the PG-induced [Ca2+]i
      rise. The second phase of the [Ca2]i rise was fallen fast by nicardipine (10
      micro M), but not by omega-conotoxin (1 micro M). The results obtained suggested
      that the Ca2+ influx through the L- and N-type Ca2+ channels are involved in the
      PG-induced [Ca2+]i rise.

PMID- 10954125
TI  - Mechanism of mitogenic effect of fluoride on fetal rat osteoblastic cells:
      evidence for Shc, Grb2 and P-CREB-dependent pathways.
AB  - Fluoride stimulates bone cell proliferation and nodule formation in fetal rat
      calvarial osteoblastic cells. In addition, fluoride enhances alkaline phosphatase
      activity, a marker of osteoblastic differentiation, in a dose-dependent manner.
      The effects of fluoroalumino complex (AlFx) on cell proliferation and
      differentiation were markedly reduced by tyrosine kinase inhibitor; 1 mM
      genistein or 1 microg/ml herbimycin. It suggests that tyrosine kinase-mediated
      mitogenic signaling involves a series of protein-protein interactions between
      tyrosine-phosphorylated receptors, Shc and Grb2, resulting in an AlFx-induced
      mitogenic effect. The results indicate that AlFx dose-dependently enhances the
      tyrosine phosphorylation of the adaptor molecule Shc (p52) and its association
      with Grb2 in the tyrosine kinase mediated pathway. In addition, AlFx decreases
      the phosphorylation level of CREB without any change on the amount of CREB
      protein. Taken together, the results suggest that adaptor proteins, including Shc
      and Grb2 of the protein tyrosine kinase cascade are implicated in fluoride
      induced mitogenic activity of fetal rat calvarial osteoblastic cells.
      Furthermore, CREB which passes signals from cAMP to transcriptional factor CRE,
      modulates the fluoroaluminate-induced metabolism of bone cells via a decrease of
      phosphorylation level.

PMID- 10954126
TI  - Glucose does not affect catecholamine stimulus-secretion coupling in rat adrenal
      medulla: relationship to low changes in osmolarity and to insulin.
AB  - Glucose levels were analyzed to see whether they directly affect the
      catecholamine release from chromaffin cells. We incubated isolated adrenal
      medullae of rats in Krebs-Hepes modified solutions with several glucose
      concentration, in the presence and absence of carbachol or insulin. Transfer of
      the medulla from a solution with 11.1 mM of glucose to a 0.56 mM one caused an
      increase in catecholamine secretion. Relative increase in change of glucose
      levels from 25 to 0.56 mM and from 50 to 0.56 mM enhanced the effect mentioned
      above. An inhibitory effect was detected after transfer of the medulla from 0.56
      mM to 50 mM glucose. However, correction of solution osmolarity with mannitol or
      NaCl switched back catecholamine secretion to basal levels in all groups, and
      correction of solution osmolarity with sucrose indicated an impairment of
      catecholamine release. No difference was observed in stimulated catecholamine
      secretion (100 microM of carbachol) at all glucose levels. Further, the presence
      of insulin did not affect catecholamine secretion in all groups. Our results
      suggest that in isolated adrenal medullae of rats (1) glucose or variations in
      glucose levels do not affect catecholamine released; (2) isolated adrenal medulla
      of rat was highly sensitive to hyperosmolarity and extremely sensitive to
      hyposmolarity; (3) Insulin had no acute direct effect on catecholamine secretion
      in isolated adrenal medullae of rats.

PMID- 10954127
TI  - The inhibitory effect of diuretics on carbonic anhydrases.
AB  - A classification of diuretics mainly comprises mercurials; carbonic anhydrase
      inhibitors, thiazide diuretics, loop diuretics, inhibitors of renal epithelial
      Na+ channels and antagonists of mineralocorticoid receptors. We studied in this
      paper the relationship between diuretics and carbonic anhydrase (CA). Our in
      vitro and in vivo results show that all diuretics inhibit carbonic anhydrase II
      and renal CA IV. Further, our data show that they also inhibit epithelial cell CA
      in the renal tubules. The changes in intracellular pH (pHi) induced by these
      diuretics through CA inhibition would influence: a) the coupling to their
      receptors affecting information transmission to the epithelial cells of renal
      tubules as well as diuretic response; b) the decrease of Na+ exchanger
      (thiazide), of Na+ - K+ - 2Cl- relation (loop diuretics), Na+ channel blocking in
      distal and collecting tubules (amiloride, triamterene), as well as the antagonism
      between spironolactone and aldosterone at the mineralocorticoid receptor level,
      suggest that this competition might also be produced on CA II and on renal CA IV,
      which, in turn, could be influenced by pH-induced changes, the binding of the
      diuretic to its membrane receptor as well as the activity of the brush membrane
      or cytosolic pump. Furosemide and indapamide, diuretics known to have
      vasodilating effects, induce the fall of blood pressure that parallels the
      decrease of CA I activity. These results show the involvement of CA in the
      mechanism of action of the diuretics and in their actions associated with
      vasodilating effects. pH changes resulting from the action of CA contribute to
      the action of diuretics. All diuretics inhibit CA isozymes.

PMID- 10954128
TI  - Evaluation of cyclin D1 mRNA expression in gastric and colorectal cancers.
AB  - Cyclin D1 is a G1 cyclin that controls the transition of the cell cycle from G1
      phase to S phase, and its gene is located on chromosome 11q13. We evaluated the
      expression of cyclin D1 mRNA in surgically resected specimens of gastric and
      colorectal cancers using quantitative RT-PCR. In this method, cDNA derived from
      cyclin D1 mRNA was amplified in a tube together with an internal control. The
      expression of cyclin D1 mRNA was high in 8 of 36 gastric cancer tissues (22%) and
      9 of 27 (33%) colorectal cancer tissues, compared to normal mucosal tissues. In
      gastric cancers, the rate of cyclin D1 mRNA expression (an index of the density
      of DNA bands) was significantly higher in patients with tumors invading beyond
      the submucosal layer, regional lymph nodes and lymphatic vessels (i.e., patients
      with stage III or IV). In colorectal cancers, the rate of cyclin D1 mRNA
      expression was significantly higher in patients with venous invasion. Moreover,
      in patients with colorectal cancer, the survival rate of high-expression group
      was significantly lower than in low-expression group. Our results suggested that
      overexpression of cyclin D1 mRNA reflected the severity of gastric cancer and
      poor prognosis of colorectal cancer.

PMID- 10954129
TI  - Acute effects of estradiol and of diethylstilbestrol: pro- or antioxidant
      potential?
AB  - This study was aimed to examine the effects of a single high dose of natural and
      synthetic estrogens on the antioxidant defense enzymes in liver and blood. Female
      Wistar albino rats, four to six months old, were divided into three groups, and
      received either i.p. injections of diethylstilbestrol (DES ; 150 mg kg(-1) b.w.)
      or s.c. injections of estradiol (E2; 25 mg kg(-1) b.w.), and the third group
      (control) was injected the solvent. Animals were killed under light ether
      anesthesia three hours after injection. Cu-Zn superoxide dismutase (SOD),
      glutathione peroxidase (GPx) and catalase (Cat) enzyme activities and
      fluorometric malondialdehyde (MDA) determination were performed in liver tissue
      homogenates and in blood. Acute estradiol injection caused a significant increase
      in both MDA levels and GPx activity in liver tissue when compared to the
      controls, (p <0.05 and p <0.02; respectively). Changes in both enzyme activities
      and MDA concentration were unremarkable following acute DES injection. In blood,
      only Cu-Zn SOD activity was significantly altered in blood following E2
      injection. Although the significance of alteration in GPx activity remains
      unclear, it is most likely related to enhanced generation of lipoperoxides. A
      significant increase in MDA concentrations in liver tissue is indicative of pro
      oxidative damage rather than an antioxidant action by E2.

PMID- 10954130
TI  - Modified anticoagulant therapy factor and international normalized ratio in
      patients in an unstable coagulation state with respect to warfarin therapy.
AB  - In our pilot study of 1997, an Anticoagulant Therapy Factor (ATF) was formulated,
      compared to the International Normalized Ratio (INR) and proposed to replace the
      INR. Statistically, replacement of the INR was reasonable; but many discrepancies
      occurred when the results of ATFs and INRs were compared for individual patients.
      The study was based on patients undergoing induction of warfarin anticoagulant
      therapy, so they were "unstable" with respect to warfarin. A 1998 follow-up study
      by Carroll and Jackson based on patients "stable" with respect to warfarin,
      having taken the drug for at least six weeks, was, therefore, undertaken. In this
      study, the ATF was modified to an MATF by both multiplying the ATF by the
      prothrombin ratio (PR) and adjusting the INR-ATF linear regression analysis line
      by analytic geometry, so that the slope was one and the line passed through the
      origin. These modifications achieved both statistical and individual patient
      concordance between INRs and ATFs. The purpose of the present paper is to apply
      the techniques of the 1998 study to the original 1997 pilot study to see if the
      reprocessed data on the "unstable" patients is, in fact, also concordant with
      respect to INRs and ATFs.

PMID- 10954131
TI  - Eicosapentaenoic acid reduces thrombin-evoked release of endothelin-1 in cultured
      bovine endothelial cells.
AB  - Endothelial cells were isolated from bovine thoracic aorta and cultured. Bovine
      aortic endothelial cells (BAEC) were incubated with radiolabeled arachidonic acid
      (3H-AA) or eicosapentaenoic acid (14C-EPA) (1 microM) for 3 hr. Both fatty acids
      were predominantly incorporated into phosphatidylcholine (57 +/- 2% and 62 +/- 2%
      respectively) and slightly into phosphatidylethanolamine (11 +/- 0.5% and 12 +/-
      0.6% respectively). phosphatidylinositol (26 +/- 1.5% and 10 +/- 0.5%
      respectively) and neutral lipids (6 +/- 0.5% and 15 +/- 1% respectively). After
      BAEC incubation with 3H-AA for 24 hr with or without EPA (1 microM), the release
      of radioactive metabolites of AA induced by thrombin (5.5 U/ml) was strongly
      reduced by the preliminary treatment with EPA (72 +/- 5%). After BAEC incubation
      with AA, EPA or vehicle (control), endothelin-1 levels were measured by RIA in
      the culture medium and we observed that: 1) the basal production of endothelin-1
      was not modified after either AA or EPA treatment, 2) the thrombin-evoked release
      of endothelin-1 was significantly reduced by EPA (5.8 +/- 0.82 and 3.8 +/- 0.50
      pg/microg proteins in control and EPA-treated cells, respectively); 3) by
      contrast, AA had no significant effect on the thrombin-evoked release of
      endothelin-1. In conclusion, EPA reduces strongly the endothelin-1 release but AA
      is ineffective. This reduction of endothelin-1 release may account partly for
      some of the vascular effects of EPA.

PMID- 10954132
TI  - Hormone replacement therapy: discrepancies between evidence and recommendations.
AB  - Postmenopausal hormone therapy is widely used to prevent diseases. This is not,
      however, based on the kind of evidence that is normally required of a preventive
      drug therapy: it is based on intermediary outcomes of trials and non-experimental
      studies. Many reasons can be postulated for the fact that we know little of this
      old and widely used therapy. To remedy the current situation, we should encourage
      randomised controlled trials, reveal the insufficiency of the current evidence,
      and challenge the drug industry's biased influence.

PMID- 10954133
TI  - Women's health: issues and prospects.
AB  - An overview is presented of the research and theorizing on women's health
      accomplished over the past 25 years. This research is represented by two parallel
      strands regarding women's health: the first strand concerns the feminist and
      sociological research tradition, and the other focuses on the public health and
      epidemiological tradition. The conclusion is that Nordic research can offer new
      knowledge on women's health in both the quantitative and the qualitative research
      traditions when researchers adopt a gender-sensitive perspective.

PMID- 10954134
TI  - Back to work? Gendered experiences of rehabilitation.
AB  - Gendered experiences of rehabilitation were studied in a strategic sample of
      young people with work-related disorders. Thematic interviews were conducted with
      seven women and four men, and analysed from a gender perspective using grounded
      theory. In comparison with women, men were more likely to receive specific
      diagnoses, to demand actions, and to strive for full-time waged work. Women
      experienced more often than men that doctors distrusted them, and that social
      insurance officers made decisions for them. The outcome of rehabilitation was
      better for men, whether they adapted to the offered measures or not. Gendered
      structures in the rehabilitation system, the construction of gender in the
      meeting between the client and the doctor/social security officer, as well as the
      division of domestic duties within marriage, strongly influenced the outcome of
      the rehabilitation process in favour of men.

PMID- 10954135
TI  - Single-parent family background and physical illness in adulthood: a follow-up
      study of the Northern Finland 1966 birth cohort.
AB  - The association between single-parent family background and physical illness in
      early adulthood was studied in a sample of an unselected, general population: the
      Northern Finland 1966 Birth Cohort. Between the ages of 16 and 28 years, women of
      single-parent family background were more commonly treated (61% versus 57%) for
      any physical condition in hospital wards compared with women of two-parent family
      background. Spontaneous abortions (odds ratio; OR = 1.4, 95% CI 1.0-2.0),
      complications of pregnancy (OR = 1.1, 95% CI 1.0-1.3), and intracranial injuries
      (OR = 2.0, 95% CI 1.0-3.8) were more common among women with single-parent family
      background. They also had a clearly higher risk for induced abortions (OR = 1.6.
      95% CI 1.4-1.9), and a higher incidence of deliveries than did other women. The
      risk of hospital-treated physical illness did not differ between men of single
      parent and two-parent family background. Poisonings and injuries were, however,
      more common reasons for hospital admission among men with single-parent family
      background than among other men. In conclusion, our main finding was that, among
      women, an association between overall hospital-treated physical illness and
      single-parent family background does exist. However, offspring of single-parent
      families are mostly in as good physical health as others.

PMID- 10954136
TI  - Effects of performance-based reimbursement in healthcare.
AB  - The aim of this study was to assess changes in attitudes and behaviour related to
      efficiency and quality of care after introduction of performance-based
      reimbursement. The study consisted of two parts. Part One was performed in 1992
      94 as a repeated cross-sectional study of physicians in Stockholm County Council
      working with a newly introduced performance-based reimbursement system. Part Two
      was a similar study conducted in 1994 in 11 Swedish councils without performance
      based reimbursement. The results show a significant difference between the two
      groups of physicians in attitudes concerning changes in quality of care and
      premature discharge from hospital. Despite concern about quality and premature
      discharge, physicians in Stockholm were found to have changed their behaviour in
      that the average length of stay in 1994 was about one day shorter in Stockholm
      than in the other 11 county councils. This indicates that the performance-based
      reimbursement system may strengthen the incentive to increase efficiency.

PMID- 10954137
TI  - Surveys on attitudes to active euthanasia and the difficulty of drawing normative
      conclusions.
AB  - PURPOSE: To present surveys on active euthanasia and to discuss what normative
      conclusions can be drawn. METHODS: Two summary articles and 30 recent surveys on
      attitudes to active euthanasia are discussed. RESULTS: According to the first
      summary article, acceptance of active euthanasia among the public has stabilized
      around 65%; according to the second, almost 60% of physicians are in favour of
      legalizing active euthanasia. As for the 30 recent surveys, physicians are most
      often respondents. while the general public is surveyed in only three. The
      differences in attitudes are striking: 21-78% answered that active euthanasia
      should be legalized, and 14-51% rejected this idea. The core of the general
      problem of drawing normative conclusions from empirical data is first addressed;
      then we discuss the principles of autonomy and beneficence, which are often
      referred to in arguments for and against euthanasia.

PMID- 10954138
TI  - Effects of job characteristics, team climate, and attitudes towards clinical
      guidelines.
AB  - The aim of this study was to form and test a model of the antecedents and
      possible moderators of the use of clinical guidelines among healthcare
      professionals. A postal questionnaire survey of all workers in six health centres
      around Finland. was carried out in April 1996. The health centres were selected
      to represent all different areas of Finland. A total of 748 (65.5%) of the
      healthcare workers completed and returned the questionnaire. Of the respondents
      95% were women, 16% physicians or dentists, 31% registered nurses, and 27%
      practical nurses. It was hypothesized that besides positive attitudes towards
      guidelines, job characteristics and team climate affect the use of guidelines.
      Three alternative models of possible main and moderating effects of attitudes,
      job characteristics, and team climate were formed and tested. These models were
      tested using hierarchical regression analysis and structural equation modelling
      (LISREL8). All of the hypothesized main effects and the moderating effect of job
      characteristics between attitudes towards and the use of guidelines were
      supported. According to our results important factors behind the general positive
      or negative attitudes towards guidelines are the usefulness, reliability,
      practicality, and availability of the guidelines. Also, the overall individual,
      team, and organizational competence to follow the procedures recommended, seemed
      to be vital. Moreover, those whose job motivation potential was high were more
      ready to use clinical guidelines even when their attitudes towards guidelines
      were the same.

PMID- 10954139
TI  - High demand, low control, and impaired general health: working conditions in a
      sample of Swedish general practitioners.
AB  - This cross-sectional survey of 1,004 Swedish general practitioners (GPs) aged 32
      64 years analyses the extent to which low control, high work demand, and other
      work-related conditions are associated with self-rated impaired general health
      and impaired quality of life among Swedish GPs. The first part of the
      questionnaire contained "SF-36 Health Survey", from which we chose five
      psychosocial multi-item scales as dependent variables. The second part of the
      questionnaire had questions about working conditions from "The Swedish Survey of
      Living Conditions". Unconditional logistic regression was used. Female and male
      GPs with high job strain, i.e. low control and high work demand, exhibited a more
      than threefold increased risk of impaired general health compared with those with
      medium job strain. Low job strain among male GPs was associated with a low risk
      of impaired health. The finding of significant associations between psychosocial
      working conditions and impaired general health and impaired, quality of life in
      GPs in 1996 highlights the need to improve working conditions in Swedish primary
      healthcare, for example, by reducing number of inhabitants per full-time GP to
      1,500.

PMID- 10954140
TI  - Injuries to boys and girls in Swedish schools: different activities, different
      results?
AB  - The study examines gender-related injury frequency by the type of school
      activity. Data were taken from an injury register created during the school year
      1996/97 with the help of 79 Swedish public-sector schools. Injury ratios (IRs) by
      gender, type of municipality, and type of school were computed for injuries
      during all types of activities, for sports-related injuries, and for injuries
      sustained during recess periods. IRs were higher among boys for recess
      activities, and among girls for sports activities. IRs showed major variation by
      type of school, and minor variation by type of municipality. Schools catering for
      pupils aged 7-12 years had the highest IRs for all groups of injuries, both on
      aggregate and by gender. Gender-related injury-event occurrence at school clearly
      varies with kind of activity, but less so with age of pupils. The extent to which
      this reflects individual differences rather than varying exposure is uncertain.

PMID- 10954141
TI  - Psychometric properties of the Swedish version of the Well-Being Questionnaire in
      a sample of patients with diabetes type 1.
AB  - OBJECTIVES: The aim of the present investigation was to further test the
      psychometric properties of a Swedish version of the Well-Being Questionnaire
      (WBQ) in order to determine whether it could be suitable for measuring health
      related quality of life among type 1 diabetic patients. METHODS: In total, 94
      patients who fulfilled the inclusion criteria were selected for the study and of
      these 85% participated. Reliability was tested with Cronbach's alpha coefficient
      and the internal validity by means of principal component analysis and multitrait
      analysis. To test the external validity, comparisons were made with two other
      questionnaires, the Short form-36 and a Swedish Mood Adjective Check List.
      RESULTS: The results show that, above all, the Swedish version of the WBQ
      measures psychological well-being, and thus must also be complemented with scales
      that measure other consequences of the illness and/or treatment, i.e. physical
      symptoms. The questionnaire has low discriminatory validity between subscales,
      which casts doubt on the appropriateness of using the four subscales as separate
      measures. The two scales measuring anxiety and depression are not sensitive
      enough for use among type 1 diabetics without complications and high or normal
      levels of psychological well-being. CONCLUSIONS: The Well-Being Questionnaire
      alone does not give any more information about subjective health status among
      type 1 diabetic patients than, for example, the generic SF-36.

PMID- 10954142
TI  - Criterion-validity-based assessment of four scale constructs.
AB  - BACKGROUND: The aim of this study was to discuss, in general, selected crucial
      aspects of the appropriate methodology for the development and validation of
      scales indicating health status, and to illustrate this empirically by within
      material comparison of the accuracy of four different scale constructs based on
      identical raw data. METHODS: The empirical example was based on information from
      the parents of 99 refugee children, aged 3-15 years, from the Middle East, who
      participated in a structured interview on their children's mental health.
      Following this, they were exposed to a blinded semi-structured psychological
      interview. Four anxiety scales were constructed based on answers to 12 anxiety
      symptom questions in the structured interview: Scale 1, by cumulation of original
      item scores, each ranging from 0 to 3; Scale 2, by counting the number of
      symptoms being present; Scale 3, by counting the number of frequent or intense
      anxiety symptoms; Scale 4, by estimation of the multivariate probability of the
      child being anxious, as assessed by the psychological interview. The scales were
      compared for their accuracy in the identification of children assessed as anxious
      by psychological interview. RESULTS: The four scales correlated mutually, and
      each of them was significantly associated with anxiety, as assessed by
      psychological interview. The weighted scale, however, performed significantly
      better than the unweighted scales for sensitivity but not for specificity. In the
      present data set the overall amount of misclassification was, however,
      significantly less than in the unweighted scales. CONCLUSION: As expected from
      theory, the weighted scale was found to be superior to the unweighted scales, in
      identifying the anxious children of the empirical example. In the presence of a
      blinded criterion measurement, empirical regression-based weighting of scale
      items thus constitutes an accessible and valid alternative to traditional methods
      of health and social scaling.

PMID- 10954143
TI  - Amphetamine abuse during pregnancy: environmental factors and outcome after 14-15
      years.
AB  - The aim of this study was to assess the influence of social environmental factors
      on school performance and behavioural problems among 14-year-old children who had
      been exposed to amphetamine during foetal life. The study group comprised a
      cohort of 65 children who had suffered intrauterine exposure to amphetamine due
      to maternal drug abuse. This group has been followed since birth and examined at
      regular intervals. Information regarding the academic performance of the children
      was gathered from the school authorities. The psychosocial environment of the
      children was determined through interviews and through information obtained from
      the social authorities. Of the 64 children who attended a school within the state
      school system, 10 (15%) were a year behind for their age. The mean grades were
      significantly lower than those of their classmates. Behavioural problems were
      mentioned in the social authority documentation of one-third of the children,
      regardless of whether the child was placed in a foster home or was residing with
      the biological mother. A positive significant correlation was found between
      maternal age and the outcome of the children, as well as between therapy during
      pregnancy and outcome, whilst several environmental factors, particularly during
      the child's first four years, correlate negatively to outcome. Psychosocial
      factors early in life influence the outcome at 14 years. The positive effect of
      intervention during pregnancy illustrates the importance of early identification
      preferable during pregnancy.

PMID- 10954144
TI  - Illicit drug injectors' strategies for cleaning needles and syringes: findings
      from qualitative research.

PMID- 10954145
TI  - Second-generation endometrial ablation techniques.

PMID- 10954146
TI  - Interstitial thermo-ablation under MRI guidance for the treatment of fibroids.
AB  - Women with symptomatic uterine fibroids are increasingly seeking alternatives to
      open surgery. The combination of high resolution magnetic resonance imaging and
      the application of laser heat permit percutaneous treatment of fibroids under
      local anaesthetic. This article reviews the technique of interstitial thermo
      ablation and other current minimally invasive therapies for symptomatic fibroids.

PMID- 10954147
TI  - The diagnosis and management of infiltrating nodular recto-vaginal endometriosis.
AB  - This paper reviews the history of infiltrating recto-vaginal endometriosis, its
      clinical and histological diagnosis, together with discussion of treatment
      options available. Important new work demonstrates significant serious
      symptomatology which patients suffer, and the relief that can be obtained by
      radical surgical excision. However this treatment is only available in certain
      specialist centres. The appropriate methods of management are yet to be subject
      to a proper randomized control trial, and results of treatment can only be
      assessed by meticulous recording of patient signs and symptomatology pre- and
      post-operation associated with histological confirmation of the disease.

PMID- 10954148
TI  - Evidence-based management of ectopic pregnancy.
AB  - In selected cases, medical treatment of ectopic pregnancy with methotrexate is as
      effective as laparoscopic surgery. However, medical treatment might have a more
      negative impact on the health-related quality of life than surgical treatment.
      This is partly because of the long resolution time after medical treatment. New
      evidence suggests that combining methotrexate and mifepristone can shorten this
      resolution time.

PMID- 10954149
TI  - Microwave endometrial ablation in the management of menorrhagia: current status.
AB  - Menorrhagia is a common clinical problem. Recently several different ablative
      techniques have been described to treat it in the expectation of reducing
      hysterectomy rates. This paper describes the current status of microwave
      endometrial ablation, its clinical efficacy, its safety profile and future
      development.

PMID- 10954150
TI  - Controversies in the surgical management of hydrosalpinx.
AB  - The surgical management of hydrosalpinges is a controversial subject. Chronic
      pathology of the fallopian tube with distal obstruction leads to the formation of
      a hydrosalpinx, and is associated with very poor pregnancy rates after surgery.
      In these cases, in-vitro fertilization has proved to be a much better
      alternative. However, several studies have shown that patients with
      hydrosalpinges have significantly lower pregnancy and implantation rates after in
      vitro fertilization compared with patients with other forms of tubal damage. The
      exact mechanism by which the hydrosalpinx adversely affects in-vitro
      fertilization results is not yet fully understood. The value of performing a
      salpingectomy before in-vitro fertilization has been studied extensively.
      Currently, a clear benefit in salpingectomies has been proved for patients with
      ultrasonically visible hydrosalpinges.

PMID- 10954151
TI  - Stress responses to endoscopic surgery.
AB  - Growing evidence in the literature suggests that laparoscopic surgery should be
      performed instead of laparotomy for the treatment of pelvic benign diseases
      whenever feasible, as it results in a lower stress response on the part of the
      patient and possibly a shorter recovery time.

PMID- 10954152
TI  - Laparoscopic management of ovarian endometriomas: a critical review of current
      practice.
AB  - Endometriomas are a common cause of gynaecological morbidity, but their aetiology
      and management remain controversial This review focuses on identifying the
      evidence from published literature for the laparoscopic management of ovarian
      endometriomas. A critical appraisal shows that laparoscopic surgery is equivalent
      to laparotomy. There is no evidence to suggest that one minimal access surgical
      technique is clearly superior to another. However, this may be related to the
      inconsistencies in study design. In view of this we describe and justify our own
      management strategy for dealing with endometriomas.

PMID- 10954154
TI  - Enterocele repair and vaginal vault suspension.
AB  - A paradigm shift has occurred in the approach to enterocele repair and vaginal
      vault suspension. This change in our approach is based on anatomic dissections
      that demonstrate that the loss of the upper suspensory fibers of the paracolpium
      and parametrium lead to uterine prolapse and vaginal prolapse after hysterectomy.
      In addition, the separation of the pubocervical from the rectovaginal fascia
      results in apical enterocele where the peritoneum is in contact with the vaginal
      mucosa. These fascial defects are hernias, and appropriate herniorraphy
      techniques will correct these defects and result in successful reconstruction of
      the vaginal tube and its reattachment to the suspensory cardinal uterosacral
      complex.

PMID- 10954153
TI  - A cost-effective approach to the management of endometriosis.
AB  - Endometriosis is a common disease that affects a large number of women throughout
      the world. Whereas in the past laparoscopy was commonly used for the diagnosis
      and treatment of women with endometriosis and pelvic pain, recent studies have
      demonstrated that surgical therapy offers no better results in terms of pain
      relief than medical therapy with a gonadotrophin-releasing hormone agonist.
      Surgical therapy requires considerable experience and expertise on the part of
      the surgeon and the results are likely to be operator dependent. The results of
      the very best surgeons, as published in the medical literature, often cannot be
      replicated by the average gynecologist. Medical treatment, on the other hand, is
      not operator dependent. The efficacy of clinical diagnosis given a thorough
      evaluation has been proved, and the outcomes of empiric medical therapy with a
      gonadotrophin-releasing hormone agonist are substantial. Given the similar
      results obtained with a gonadotrophin-releasing hormone agonist and surgical
      intervention and the fact that medical treatment is less expensive, primary
      therapy with a gonadotrophin-releasing hormone agonist appears to be the most
      cost-effective approach to the management of endometriosis and pelvic pain.
      Because of the limited information currently available, a statement regarding
      endometriosis and infertility would probably be inappropriate at this time.

PMID- 10954155
TI  - Bibliography. Current world literature. Endoscopic surgery.

PMID- 10954156
TI  - Mycobacterium tuberculosis and human macrophage: the bacillus with "environment
      sensing".

PMID- 10954158
TI  - Ultrastructural analysis of v-myb oncogene product cooperation with components of
      avian cell nuclear matrix.
AB  - The cooperation of the v-Myb oncoprotein with extracted nuclear matrix of avian
      haematopoietic cells expressing the v-myb oncogene was studied by means of
      immunoelectron microscopy. The nuclear matrix was extracted by a gentle method of
      detergent treatment at moderate ionic strength and visualized either in ultrathin
      LR White sections, in unembedded resin-free sections, and in addition by the
      aqueous spreading technique. Using anti-Myb polyclonal antibody we have shown
      interaction of the v-Myb protein product with extracted nuclear matrix. This
      oncoprotein, however, was easily released from the structure by a detergent as
      well as by DNAase treatment and ammonium sulphate extraction. Prefixation of
      structures before detergent treatment prevented this extraction. The v-Myb
      protein marker was distributed in clusters or associated with fibrillar
      structures in most cases. Single markers decorating these fibrillar or less dense
      structures were also detected.

PMID- 10954157
TI  - Genes involved in the destruction of leukaemic cells by induced photosensitivity.
AB  - Gene expression changes were observed in the HEL and HL-60 cell lines after the
      stimulation of protoporphyrin IX synthesis by ALA administration and photodynamic
      process induction. Isolated ribonucleic acids were radiolabelled by reverse
      transcription, and the cDNA obtained was hybridized to membrane macroarrays
      (Clontech 7742-1) containing 588 gene probes. Besides changes in the activity of
      genes supposed to be involved in the programmed cell death and DNA reparation
      processes, increased or diminished transcription activity was also observed in
      several other genes; the reason for this phenomenon was not clear. The activation
      of programmed-cell-death genes appeared after the ALA load application,
      indicating the toxic effect of ALA. The gene expression changes observed in the
      two cell lines differed substantially, only a few of them were common for both
      cell lines.

PMID- 10954159
TI  - Aggregated and monomeric forms of proteins in boar seminal plasma:
      characterization and binding properties.
AB  - Boar seminal plasma was separated into five protein fractions (I-V) (>100, 55,
      45, 30, 5-15 kDa) by gel filtration chromatography on Sephadex G-75 SF at pH 7.4.
      RP HPLC of protein fractions I-V and N-terminal sequencing of their individual
      components revealed that high-molecular-weight aggregates consisted mainly of DQH
      sperm surface protein and AQN, AWN, PSP II spermadhesins, while fraction IV
      consisted of heterodimers of PSP spermadhesins only. Spermadhesins as monomers
      were present in seminal plasma in a very low amount. Biotinylated fractions I-IV
      containing AWN, AQN, DQH, and PSP proteins were bound to boar epididymal and
      ejaculated spermatozoa with the same efficiency. Aggregates containing AWN, AQN,
      DQH, PSP II proteins (fractions I-III) and their HPLC-separated monomeric forms
      interacted with phosphorylcholine. Aggregates containing the DQH protein and AWN
      spermadhesins as well as their separated monomeric proteins interacted strongly
      with acidic polysaccharides. PSP II interacted with some acidic polysaccharides,
      while the fraction IV corresponding to heterodimer PSP IPSP II did not show any
      binding to acidic polysaccharides and zona pellucida. Fractions I-III showed
      affinity to cholesterol. The strongest interaction was observed between
      biotinylated glycoproteins of porcine zona pellucida and AWN 1-containing
      aggregates and separated proteins. AQN 1 spermadhesin effectively blocked the
      sperm binding to oocytes. These results suggest that under physiological
      conditions, the aggregated forms of seminal plasma proteins (DQH, AQN, AWN, PSP
      II) rather than the individual proteins might take part in coating the sperm
      surface, in sperm capacitation and in primary binding of spermatozoa to zona
      pellucida of the ovum.

PMID- 10954160
TI  - HLA-A, HLA-B and HLA-C polymorphism in the Slovak population.
AB  - The occurrence rates of class I HLA alleles were investigated in a sample of the
      Slovak population by a PCR-SSP method. The frequencies of HLA-A alleles ranged
      from 0.00 for A*4301 to 0.2798 for A*0201-22; the frequencies of HLA-B alleles
      ranged from 0.00 for B 4601,B* 4801-3, B*5901,B* 7301, and B* 8101 to 0.1101 for
      B* 4402-10, and those of HLA-C alleles from 0.00 for Cw*1301 and Cw* 1402-3 to
      0.2661 for Cw 0701-10. The occurrence rates of class I HLA alleles established in
      our study were compared with those in the Czech population. No significant
      differences were found.

PMID- 10954161
TI  - Tissue-engineered skin in the treatment of vitiligo lesions.
AB  - Vitiligo is characterized by the loss of skin pigmentation due to the destruction
      of melanocytes. Its treatment is usually difficult. For stable cases, melanocyte
      transplantation is the method of choice. A newly developed treatment with
      recombined human/porcine skin methodology, permitting easy handling of the graft,
      is described in the present work. In five vitiligo patients, autologous epidermal
      cells were obtained from pigmented thin skin biopsies. The cells were cultured on
      a dried cell-free porcine dermis by the 3T3 feeder layer technique. After 10 days
      melanocytes were regularly dispersed in confluent keratinocyte cultures. Upside
      down delivery of epidermal cells was used. The epidermal layer was directly
      applied onto a dermabraded vitiligo lesion, with porcine dermis covering the
      lesion. Pigmentation started to be visible 4-6 weeks after grafting. After using
      the above described methodology, the pigmentation appeared in the range of 65-80%
      of the grafted area. Additional UVA irradiation enhanced the treatment success up
      to 100%. The surgical vitiligo treatment appears to be a reasonable method of
      choice in stable vitiligo cases of a disease lasting for at least two years,
      which means for approximately 5% of all vitiligo patients.

PMID- 10954183
TI  - Animal models: are they useful for the investigation of gastrointestinal disease?

PMID- 10954184
TI  - Experimental models of acute pancreatitis: are they suitable for evaluating
      therapy?
AB  - Since randomized controlled studies of severe acute human pancreatitis can be
      performed only with restrictions, at least some aspects of innovative therapy
      concepts should first be clarified in animal experiments. In vitro trials are
      inadequate for this purpose since they cannot simulate the complex course of
      severe acute pancreatitis. Animal test results can be transferred to clinical
      practice if the results are based on trials with established models, standardized
      methods, and a study design imitating the clinical situation. This contribution
      discusses the demands on such an animal model of acute pancreatitis and a
      corresponding study protocol and presents models and protocols which meet these
      requirements. Concrete examples are presented to show that animal experiments are
      of great value under these conditions, especially in acute necrotizing
      pancreatitis. Further standardization of models, protocols, and monitoring should
      further improve future animal therapy studies at least to the extent that it is
      possible to select particularly promising substances, which should then be tested
      in randomized controlled trials.

PMID- 10954185
TI  - Animal models of exocrine pancreatic cancer.
AB  - Clinically and biologically relevant animal models are mandatory to further
      evaluate both the pathophysiology and novel strategies for diagnosis and
      treatment of exocrine pancreatic cancer. This review briefly summarizes the
      features of human pancreatic cancer in order to define requirements for animal
      models of the disease. The described model systems in rodents include pancreatic
      cancer induced by chemicals, pancreatic cancer in transgenic, and immunodeficient
      animals.

PMID- 10954186
TI  - Animal models of intestinal inflammation: new insights into the molecular
      pathogenesis and immunotherapy of inflammatory bowel disease.
AB  - Inflammatory bowel diseases (IBDs) in humans are complex chronic inflammatory
      disorders of largely unknown cause. Several mouse models that in some respects
      resemble human IBDs have recently been developed and have provided new insights
      into immunoregulatory processes in the gut. Both genetic and environmental
      factors have been shown to be involved in chronic intestinal inflammation. In
      most of the models CD4+ T lymphocytes have been identified as central mediators
      of inflammation. Inappropriate activation of T(H)1-dominated cytokine pathways
      upon contact with luminal bacterial antigens and lack of tolerance appear to be
      crucial for intestinal pathology. We present a brief overview of important animal
      models of IBD and describe the recent progress in understanding the mechanisms
      that contribute to chronic intestinal inflammation. Furthermore, novel
      immunotherapeutic approaches derived from such animal models are discussed.

PMID- 10954187
TI  - Cryotherapy for liver metastases.
AB  - Cryotherapy is undergoing a renaissance in the treatment of nonresectable liver
      tumors. In a prospective case control study we assessed the morbidity, mortality,
      and efficacy of hepatic cryotherapy for liver metastases. Between January 1996
      and September 1999 a total of 54 cryosurgical procedures were performed on 49
      patients (median age 66 years, 21 women) with liver metastases. Patient, tumor,
      and operative details were recorded prospectively. Liver metastases originated
      from colorectal cancer (n=37), gastric cancer (n=3), renal cell carcinoma (n=2),
      and other primaries (n=7). Median follow-up was 13 months (1-32). The median
      number of liver metastases was 3 (range 1-10) with a median diameter of 3.9 cm
      (range 1.5-11). Twenty-one patients (43%) had cryoablation only, and 28 (57%) had
      liver resection in combination with cryoablation. One patient (2%) died within 30
      postoperative days. Another 13 patients (27%) developed reversible complications.
      In 19 of 25 patients (76%) with preoperatively elevated serum CEA and colorectal
      metastases it returned to the normal range postoperatively. Twenty-eight patients
      (57%) developed tumor recurrence, eight of which with involvement of the
      cryosite. Overall median survival patients was 23 months, and survival in
      patients with colorectal metastases was 29 months. Hepatic cryotherapy is
      associated with tolerable morbidity and mortality. Efficacy is demonstrated by
      tumor marker results. Survival data are promising; however, long-term results
      must be provided to allow comparison with other treatment modalities.

PMID- 10954188
TI  - Liver involvement in patients operated for ulcerative colitis, with special
      reference to the association of cholangitis with colorectal dysplasia and
      carcinoma.
AB  - This study classified liver changes found in patients undergoing proctocolectomy
      for ulcerative colitis and examined whether patients with cholangitis have an
      increased risk of colorectal dysplasia and carcinoma. The patients were 152 who
      underwent liver biopsy during surgery for ulcerative colitis. Prior surveillance
      colonoscopy specimens and operative liver and proctocolectomy specimens were
      examined histologically. Patients with dysplasia or carcinoma in colorectal
      specimens were pair-matched to patients without such neoplasia. Sixteen (10.5%)
      patients had histological features consistent with small-duct primary sclerosing
      cholangitis on liver biopsy, five of them showing normal liver function values.
      Of the 152 patients 4 were found to have colon carcinoma (2.6%) and another 4 low
      grade dysplasia (2.6%) either upon colonoscopy or in colectomy specimens. The
      median duration of the colitis in the 8 patients with colorectal neoplasia was 12
      years (range 2-29) and in the other 142 patients 4 years (0.1-33; P=0.007). The
      prevalence of primary sclerosing cholangitis (PSC) or cholangitis was 50% in
      cases with colorectal neoplasia and 13% in pair-matched controls without
      colorectal neoplasia. In this selected group of patients operated on for
      ulcerative colitis the prevalence of histological cholangitis was thus higher
      than that of PSC in previous epidemiological studies. In addition, the prevalence
      of PSC or cholangitis was much higher in cases with colorectal neoplasia than in
      pair-matched controls without colorectal neoplasia. Our results support the view
      that cholangitis constitutes an additional risk factor underlying colorectal
      dysplasia or carcinoma.

PMID- 10954189
TI  - Cholangitis in ulcerative colitis--a risk factor for colonic malignancy?

PMID- 10954190
TI  - The role of obesity on the recurrence of pilonidal sinus disease in patients, who
      were treated by excision and Limberg flap transposition.
AB  - Recurrence of pilonidal sinus disease after surgical intervention is not a very
      rare problem although sophisticated reconstruction procedures have been
      developed. Recurrence is thought to be related to the anatomical status of the
      patients, i.e., depth of the intergluteal groove. Obese patients have deeper
      intergluteal grooves. The aim of this study was to use body mass index (BMI) as
      an objective indicator of obesity to determine whether there is a relationship
      between BMI and recurrence of pilonidal sinus disease. BMI was calculated
      preoperatively in 114 patients with pilonidal sinus disease who were treated by
      excision and Limberg flap transposition between 1996-1999 in general surgery
      departments of two university hospital clinics. Fifteen patients were referred to
      our clinics after surgical intervention carried out at other institutions. Their
      average BMI was calculated by using their hospital records. The mean follow-up
      period was 24 months (range 10-36). Six of the 114 patients (5%) had recurrence.
      The mean BMI of patients with and without recurrence was 29.35 and 27.415,
      respectively (P<0.05). The mean BMI of 15 patients referred to us because of
      recurrent disease was 29.41; however, that of patients with primary pilonidal
      sinus disease was 27.212 (P<0.05). Their BMI before their first operation was
      29.30. This was also significantly higher than patients with primary disease
      (P<0.05). We conclude that obese patients with high BMI have a higher risk of
      recurrence of pilonidal sinus disease after surgical intervention.

PMID- 10954192
TI  - Volvulus of the splenic flexure of colon: a case report and review.
AB  - We report a case of splenic flexure volvulus in a patient who had previously been
      operated upon for a sigmoid volvulus. The clinical features and management of
      splenic flexure volvulus are discussed.

PMID- 10954191
TI  - Diagnostic imaging in Crohn's disease: comparison of magnetic resonance imaging
      and conventional imaging methods.
AB  - Conventional enteroclysis remains the method of choice in the diagnosis of
      inflammatory small bowel disease. The reported sensitivity rates, however, for
      the diagnosis of extraintestinal processes, such as fistulae and abscesses, are
      moderate. Computed tomography (CT) is the method of choice for the diagnosis of
      extraintestinal complications. The anatomical designation of the affected bowel
      segment may, however, prove difficult due to axial slices, and the applied
      radiation dose is high. The use of magnetic resonance imaging (MRI) in the
      diagnosis of inflammatory small bowel disease is a relatively new indication for
      the method; prerequisites were the development of breathhold sequences and phased
      array coils. Optimized magnetic resonance tomographic imaging requires a combined
      method of enteroclysis and MRI, which guarantees an optimal filling and
      distension of the small bowel. The high filling volume leads to a secondary
      paralysis of the small bowel and avoids motion artifacts. In a trial of 84
      patients with histological and endoscopic correlation the sensitivity in
      diagnosing inflammatory bowel disease was 85.4% for enteroclysis and 95.2% for
      MRI, and the specificity was 76.9% for enteroclysis and 92.6% for MRI. As none of
      the abscesses was diagnosed with enteroclysis, the sensitivity was 0% for
      enteroclysis, but 77.8% for MRI. The sensitivity in diagnosing fistulae was 17.7%
      for enteroclysis and 70.6% for MRI. In summary, MRI can detect the most relevant
      findings in patients with inflammatory small bowel disease with an accuracy
      superior to that of enteroclysis.

PMID- 10954193
TI  - Intussusception of the vermiform appendix: preoperative colonoscopic diagnosis of
      two cases and review of the literature.
AB  - Intussusception of the appendix is an uncommon condition, and the diagnosis is
      rarely made preoperatively. Making an accurate diagnosis before laparotomy is
      important in providing the optimal treatment for the patient. We present the
      clinical and endoscopic features of two cases of intussusception of the appendix
      and review the literature. Diagnosis was made preoperatively by colonoscopy in
      these cases and an elective appendectomy was performed. Appendiceal
      intussusception should be considered in the differential diagnosis of abdominal
      pain. Colonoscopy can be a valuable tool in establishing this diagnosis and in
      selecting the appropriate management.

PMID- 10954194
TI  - Pseudoxanthoma elasticum revealed.

PMID- 10954195
TI  - Cytochrome c oxidase assembly factors with a thioredoxin fold are conserved among
      prokaryotes and eukaryotes.
AB  - Cytochrome c oxidase (COX) is a multi-subunit terminal oxidase of the eukaryotic
      respiratory chain involved in the reduction of oxygen to water. Numerous lines of
      evidence suggest that the assembly of COX is a multi-step, assisted process that
      depends on several assembly factors with largely unknown functions. Sco1/2
      proteins have been isolated as high-copy number suppressors of a deletion of
      copper chaperone Cox 17, implicating Sco1/2 in copper transport to COX subunits I
      or II. Here I report the similarity of Sco1/2 assembly factors to peroxiredoxins
      and thiol:disulfide oxidoreductases with a thioredoxin fold, suggesting that Sco
      related proteins perform a catalytic rather than a copper transport function.
      Reported sequence similarities, together with the functional role of bacterial
      Sco-related proteins suggest that Sco-related proteins represent a new class of
      membrane-anchored thiol:disulfide oxidoreductases involved in COX maturation.

PMID- 10954196
TI  - Structural biology: the foundation of molecular medicine.

PMID- 10954197
TI  - Ligand-binding sites in Ig-like domains of receptor tyrosine kinases.
AB  - Receptor tyrosine kinases are cell-bound, membrane-spanning receptors that
      transduce growth factor dependent signals to the intracellular environment. Their
      catalytic cytoplasmic domains share a high level of sequence similarity, but
      their extracellular portions usually have a highly variable, multiple-domain
      structure. In a growing number of cases immunoglobulin-like domains contained
      within the extracellular portion have been shown to contain the ligand-binding
      site. In recent years experimental three-dimensional structures have been
      determined for some of these domains, free or in complex with their ligand. Here
      we review current structural information on these immunoglobulin-like domains and
      the growth factors that bind to them, with an emphasis on the vascular
      endothelial growth factor, nerve growth factor, and fibroblast growth factor
      systems.

PMID- 10954198
TI  - Structural studies of matrix metalloproteinases.
AB  - The zinc- and calcium-dependent family of proteins called the matrix
      metalloproteinases are collectively responsible for the degradation of the
      extracellular matrix. Members of this family such as the collagenases,
      stromelysins and the gelatinases are involved in the routine tissue remodelling
      processes such as wound healing, embryonic growth and angiogenesis. Under normal
      circumstances the proteolytic activity of these proteins are precisely controlled
      at the transcriptional level, the production of the proteins in their inactive
      zymogen forms and also by the co-secretion of endogenous inhibitors. Imbalance
      between the active enzymes and their natural inhibitors leads to the accelerated
      destruction of connective tissue associated with the pathology of diseases such
      as rheumatoid and osteoarthritis. The potential for using specific enzyme
      inhibitors as therapeutic agents to redress this balance has led to intensive
      research focused on the design, syntheses and molecular structural analyses of
      low molecular weight inhibitors of this family of proteins. This review describes
      the essential structural principles and molecular interactions implicated in the
      innovation of matrix metalloproteinase inhibitors and discusses the features
      necessary for the specific inhibition of the collagenases.

PMID- 10954199
TI  - Recent developments in structure-based drug design.
AB  - Structure-based design has emerged as a new tool in medicinal chemistry. A
      prerequisite for this new approach is an understanding of the principles of
      molecular recognition in protein-ligand complexes. If the three-dimensional
      structure of a given protein is known, this information can be directly exploited
      for the retrieval and design of new ligands. Structure-based ligand design is an
      iterative approach. First of all, it requires the crystal structure or a model
      derived from the crystal structure of a closely related homolog of the target
      protein, preferentially complexed with a ligand. This complex unravels the
      binding mode and conformation of a ligand under investigation and indicates the
      essential aspects determining its binding affinity. It is then used to generate
      new ideas about ways of improving an existing ligand or of developing new
      alternative bonding skeletons. Computational methods supplemented by molecular
      graphics are applied to assist this step of hypothesis generation. The features
      of the protein binding pocket can be translated into queries used for virtual
      computer screening of large compound libraries or to design novel ligands de
      novo. These initial proposals must be confirmed experimentally. Subsequently they
      are optimized toward higher affinity and better selectivity. The latter aspect is
      of utmost importance in defining and controlling the pharmacological profile of a
      ligand. A prerequisite to tailoring selectivity by rational design is a detailed
      understanding of molecular parameters determining selectivity. Taking examples
      from current drug development programs (HIV proteinase, t-RNA transglycosylase,
      thymidylate synthase, thrombin and, related serine proteinases), we describe
      recent advances in lead discovery via computer screening, iterative design, and
      understanding of selectivity discrimination.

PMID- 10954200
TI  - Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause
      pseudoxanthoma elasticum.
AB  - We recently published the precise chromosomal localization on chromosome 16p13.1
      of the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited
      disorder characterized by progressive calcification of elastic fibers in skin,
      eye, and the cardiovascular system. Here we report the identification of
      mutations in the gene encoding the transmembrane transporter protein, ABC-C6
      (also known as MRP-6), one of the four genes located in the region of linkage, as
      cause of the disease. Sequence analysis in four independent consanguineous
      families from Switzerland, Mexico, and South Africa and in one non-consanguineous
      family from the United States demonstrated several different mis-sense mutations
      to cosegregate with the disease phenotype. These findings are consistent with the
      conclusion that PXE is a recessive disorder that displays allelic heterogeneity,
      which may explain the considerable phenotypic variance characteristic of the
      disorder.

PMID- 10954201
TI  - Polymorphisms in the genes encoding platelet-derived growth factor A and alpha
      receptor.
AB  - Platelet-derived growth factors (PDGFs) may play an important role in the
      development of atherosclerosis acting as chemoattractants and mitogens for
      vascular smooth muscle cells and macrophages. Three dimeric forms of PDGF (AA,
      AB, BB) have different activities due to distinct binding properties mediated by
      two types of PDGF receptors (Ralpha, Rbeta). To investigate the possible
      contribution of molecular variants in the human PDGF-A and PDGF-Ralpha genes to
      coronary heart disease we screened these genes for polymorphisms by polymerase
      chain reaction/single-strand conformation polymorphism analysis. A total of 600
      men with myocardial infarction and 717 age-matched male controls from four
      populations in Northern Ireland and France (the ECTIM Study) were gneotyped for
      newly identified polymorphisms in the genes encoding PDGF-A (C-26IN3T, H69H,
      C+12IN5T) and PDGF-Ralpha [-1630 I/D (+/-AACTT), A-1506G, C-1390G, G-956A, C
      908A, G-793T, +69 I/D (+/-GA)] using allele-specific oligonucleotides. All PDGF
      Ralpha polymorphisms, except C-908A, involving a nucleotide change in a common
      consensus site for GCF and SP-1 transcription factors, were in nearly complete
      association, generating two major haplotypes. The PDGF-A and PDGF-Ralpha
      polymorphisms provided a heterozygosity of 0.69 and 0.40, respectively. Genotype
      and allele frequencies of the PDGF-A and PDGF-Ralpha polymorphisms did not differ
      between patients with myocardial infarction and controls in either country. None
      of the polymorphisms investigated was associated with blood pressure, coronary
      artery stenosis, or any biochemical parameter available in the ECTIM Study.

PMID- 10954202
TI  - Analysis of differentially regulated mRNAs in peripheral blood monocytes of
      berylliosis patients after in vitro stimulation.
AB  - In berylliosis and other granulomatous diseases the macrophage is regarded as
      effector cell in granuloma formation. However, little is known about granuloma
      associated regulation of genes in these cells. Differential display reverse
      transcription polymerase chain reaction (DDRT-PCR) is an attractive method for
      detection of differentially expressed genes. Since DDRT-PCR requires a comparably
      low quantity of RNA, its application to rare and limited amounts of clinical
      samples is convenient. In the present study we applied DDRT-PCR in a multiple and
      complex comparison of expressed sequence tags induced in response to various
      granuloma-associated and control stimuli. Since we are interested in granuloma
      restricted changes, we tested peripheral blood monocytes from berylliosis
      patients by DDRT-PCR stimulated with up to nine different stimuli, including
      BeSO4, the causal agent of berylliosis. Comparison of a total of 1663 sequence
      tags in four berylliosis patients revealed a mean of 32.5-37.4% differentially
      regulated sequence tags in peripheral blood monocytes of berylliosis patients,
      caused by stimuli including beryllium or Mycobacterium tuberculosis and control
      stimuli such as Latex or Zymosan. In 7.7-28.0% of the analyzed sequence tags we
      detected a differential regulation restricted to the presence of granuloma
      associated stimuli BeSO4, HgS, LiCO3, NiSO4, lipopolysaccharide, and/or heat
      killed M. tuberculosis; 1.4-12.3% were induced by more than one granuloma
      associated stimulus. Alterations associated with BeSO4 and one of the named
      stimuli were detected in 1.4-4.5%. An exclusive association with BeSO4 was found
      in 2.6-5.7% of the analyzed sequence tags.

PMID- 10954203
TI  - Modulation of urokinase-type and tissue-type plasminogen activator occurs at an
      early stage of progressing stages of chronic venous insufficiency.
AB  - Chronic venous insufficiency (CVI) progresses through a series of clinical
      stages, from healthy skin to poorly healing leg ulcers. The aim of this study was
      to analyse the distribution pattern and activity level of urokinase-type (uPA)
      and tissue-type plasminogen activators (tPA) in normal skin and in tissue
      biopsies of progressing stages of CVI, prior to and including venous ulceration.
      Biopsies 6 mm thick were taken from 14 healthy volunteers and 37 patients with 5
      different stages of CVI: telangiectases; stasis dermatitis; hyperpigmentation;
      lipodermatosclerosis; and leg ulcer. Changes in the enzymatic activity and
      spatial localization of uPA and tPA during the progression of CVI were examined
      using in situ histological zymography. Normal skin and skin with telangiectases
      showed a punctate PA activity, consisting of both uPA and tPA activity. As CVI
      progressed, an increase in the distribution of uPA and a decrease in tPA activity
      was observed. The spatial localization of uPA was widespread within the dermis of
      biopsies from stasis dermatitis and lipodermatosclerosis and was associated in
      particular with the dermoepidermal junction. Hyperpigmented skin revealed a
      pattern of PA expression similar to that of healthy skin. However, leg ulcer
      specimens exhibited peak levels of uPA with little tPA. Furthermore, a
      plasminogen-independent protease activity that was not present in any of the
      earlier stages of CVI appeared. Our results indicate that there are profound
      changes in PA activity during the progression of CVI and that these changes begin
      early in CVI, for example, in stasis dermatitis. We hypothesize that the balance
      or imbalance of the PA activity in the later stages of CVI is an important
      pathogenic factor for the development of venous leg ulcer.

PMID- 10954204
TI  - An immunohistochemical analysis of cytokine expression in allergic and irritant
      contact dermatitis.
AB  - The purpose of this study was to investigate whether the specific and non
      specific inflammatory responses to allergens and irritants give rise to immuno
      histochemical detectable differences in the cytokine profile in the skin. Skin
      biopsies taken at 0, 6, 24 and 72 h from contact allergic reactions to nickel and
      from irritant reactions to sodium lauryl sulphate were analysed. The main finding
      was that the dermal cells expressed similar patterns of cytokines (IL-1alpha, IL
      1beta, IL-2, IL-4, IL-6 and IL-10) in both types of contact reaction at 72 h.
      However, two differences were observed. Staining for the IL-1 receptor antagonist
      was more prominent in the dermis at the late stages of the allergic reaction
      compared with the late stage of the irritant reaction. The other difference was
      an increased interferon-gamma staining of infiltrating mononuclear inflammatory
      cells in the dermis in the sodium lauryl sulphate group compared with the nickel
      group. A more rapid general onset of cytokine production was found in the sodium
      lauryl sulphate group than in the nickel group. The main conclusion of this study
      was that after 6 h the cytokine patterns did not differ between the specific and
      the non-specific inflammatory responses in the skin.

PMID- 10954205
TI  - Inflammatory mediators in normal, sensitive and diseased skin types.
AB  - The role of inflammatory mediators in the pathogenesis and pathophysiology of
      skin diseases is now widely accepted. We analysed the profiles of inflammatory
      mediators in normal, sensitive (past history of eczema, but currently patch test
      negative) and diseased (psoriasis and eczema) skin types to identify the patterns
      associated with various degrees of inflammatory dermatoses. Compared with normal
      skin, prostaglandin E2 was increased approximately 3.8-fold (p<0.0002) and 4.7
      fold (p<0.0001) in suction blister fluids from sensitive and diseased skin types,
      respectively. Leukotriene B4 and interleukin-1alpha showed no differences between
      normal and sensitive skin types. However, in lesional skin from psoriasis and
      eczema patients, leukotriene B4 was increased approximately 6.6-fold (p<0.0001),
      whereas interleukin-1alpha was decreased approximately 3.1-fold (p<0.001).
      Interleukin 6 and tumour necrosis factor-alpha could not discriminate between
      skin types. We conclude that only prostaglandin E2 showed a significant stepwise
      increase on progression from normal through sensitive and inflammatory skin
      diseases. Levels of leukotriene B4 and interleukin-1alpha were also indicative of
      disease state and may be important in the pathophysiology of these conditions.

PMID- 10954206
TI  - Rat bladder epithelium: a sensitive substrate for indirect immunofluorescence of
      bullous pemphigoid.
AB  - Serological diagnosis of bullous pemphigoid is based on immunoblotting or
      indirect immunofluorescence on normal human salt-split skin. These methods are
      expensive or time-consuming and not available as a routine test in all
      laboratories. We used rat bladder epithelium as substrate for indirect
      immunofluorescence and compared it with other substrates and with immunoblotting.
      Twenty-nine bullous pemphigoid sera were studied on rat bladder epithelium,
      monkey oesophagus, salt-split skin and with immunoblotting on human keratinocyte
      cultures. Indirect immunofluorescence on rat bladder epithelium proved to be more
      sensitive (72%) than on monkey oesophagus alone (45%) and less sensitive than on
      salt-split skin (97%). Rat bladder epithelium, when tested on 41 sera of a
      control group, showed a very high specificity: 2/41 (95%). In combination with
      immunoblotting on keratinocyte extracts, indirect immunofluorescence on rat
      bladder epithelium allowed 93% of sera to be recognized, a value close to the
      salt-split skin alone. Rat bladder epithelium appears to be a more sensitive
      substrate than monkey oesophagus for the diagnosis of bullous pemphigoid and,
      although less specific, it is easier and faster than using salt-split skin, which
      remains indispensable to distinguish bullous pemphigoid from epidermolysis
      bullosa acquisita.

PMID- 10954207
TI  - Degradation of antiproteinases, complement and fibronectin in chronic leg ulcers.
AB  - It has been proposed that excessive and uncontrolled proteolytic activity is an
      important pathogenetic factor for chronic wounds. Identification of molecules
      that either control or reflect proteolysis in wounds may prove to be useful in
      determining wound healing activity. In this study wound fluid was sampled under a
      polyurethane dressing or on hydrophilic glass filters. Multiple chronic wound
      fluid components were identified; viz. the previously described alpha2
      macroglobulin, alpha1-antitrypsin and fibronectin, as well as "novel" wound fluid
      molecules such as complement factor C3, inter-alpha-inhibitor, kininogen, IgG,
      IgA, C-reactive protein, tetranectin, orosomucoid and ceruloplasmin. There
      appeared to be a highly variable degradation of alpha1-antitrypsin in the wounds;
      furthermore, the activation of C3 appeared to correlate with the appearance of
      fibronectin breakdown products. In wound fluid, inter-alpha-inhibitor was
      degraded. The influence of the sampling procedures was studied. It was shown that
      contact phase activation must be taken into account in the study of molecules
      (such as kininogens) activated by hydrophilic charged surfaces.

PMID- 10954208
TI  - Serum neopterin as an objective marker of psoriatic disease activity.
AB  - Neopterin is a non-specific marker of the activation of cell-mediated immunity.
      Several studies have demonstrated the crucial role of CD4+ T cells in the
      pathogenesis of psoriasis. We have measured serum and urine neopterin levels and
      urine neopterin/creatinine ratios by radioimmunoassay in 24 patients with plaque
      type psoriasis before and after a course of topical treatment with triamcinolone
      acetonide 0.1% and coal tar 4%. Results were compared with a group of 20 healthy,
      non-psoriatic volunteers. Serum neopterin levels were significantly elevated in
      the psoriatic group compared with the control group (p=0.001) and were
      significantly reduced after treatment (p=0.01). There was a correlation between
      pretreatment serum neopterin levels and psoriasis area and severity scores (PASI)
      (r=0.37, p=0.03) and also for pretreatment neopterin/creatinine ratios and PASI
      scores (r=0.45, p=0.01). These findings indicate that serum neopterin
      concentrations reflect disease activity in psoriasis.

PMID- 10954209
TI  - Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin
      roughness related to atopic eczema and skin dryness in a population of primary
      school children.
AB  - Non-invasive investigations of skin morphology and function are standard tools to
      study the pathophysiology of several cutaneous disorders, yet they have not been
      used in population-based epidemiological studies. Here we examined skin surface
      pH, stratum corneum hydration, trans-epidermal water loss (TEWL) and skin
      roughness by profilometry in a study population comprising 377 primary school
      children (8-9 years old) as part of a multicentre survey on risk factors for
      allergic diseases in school children. Skin surface pH showed significant higher
      values (p=0.029) in the group with atopic eczema (n=45) compared with the group
      without atopic eczema; all other parameters did not differ significantly between
      children with and without atopic eczema. With increasing skin dryness there was a
      significant increase in pH values (p=0.004). Stratum corneum hydration showed a
      significant decrease with increasing dryness (p<0.001). Measurement of skin
      roughness also revealed a significant linear relationship with skin dryness
      (p=0.02). It is concluded that measurement of skin surface pH, corneometry and
      profilometry are useful non-invasive techniques to objectively assess skin
      dryness in epidemiological studies regarding atopic skin disease.

PMID- 10954210
TI  - No increased skin reactivity in subjects with allergic rhinitis during the active
      phase of the disease.
AB  - Data on skin reactivity in patients with respiratory atopy without atopic
      dermatitis are scarce and controversial. Our purpose was to assess whether skin
      reactivity in patients with seasonal allergic rhinitis varies according to the
      phase of the disease and the possible release of inflammatory mediators acting on
      the skin during the pollen season. The volar forearm skin of eleven patients with
      seasonal allergic rhinitis without atopic dermatitis was challenged with a single
      exposure to sodium lauryl sulfate. The skin response was evaluated instrumentally
      over 72 h by transepidermal water loss, capacitance and echogenicity measurements
      for the assessment of skin damage and the inflammatory response. Tests were
      performed in winter and repeated in spring in seasonal allergic rhinitis
      patients, when they showed respiratory symptoms. Fifteen subjects with atopic
      dermatitis underwent the same experimental procedure in winter as a control
      population. Baseline and postexposure values were similar both in winter and in
      spring in seasonal allergic rhinitis patients. After sodium lauryl sulfate
      challenge, atopic dermatitis patients showed a higher degree of skin barrier
      damage and inflammation compared to patients with seasonal allergic rhinitis.
      These findings suggest that subjects with seasonal allergic rhinitis without
      atopic dermatitis have normal epidermal barrier function and normal skin
      reactivity during both the inactive and the active phase of the disease.
      Inflammatory mediators possibly released by mucous membranes during active
      allergic rhinitis do not influence skin barrier function.

PMID- 10954211
TI  - Ultrasound investigation of port wine stains.
AB  - Congenital capillary malformation, or port wine stains (PWS), have been treated
      with the pulsed dye laser since the late 1980s. Some studies have shown better
      results when the malformation has been located on the lateral face, forehead,
      neck, trunk or shoulder and inferior results, with more treatments required, when
      it is located on the central face area, dermatome V2 or the extremities. The
      purpose of this study was to determine the depth of the lesion in various
      locations. A total of 55 patients with untreated PWS were investigated with a
      high-resolution 20 MHz ultrasound system. The mean maximum depth of all PWS that
      were measurable (45 out of 55) was 1.00 mm (+/- 0.50 SD), with a range of 0.2-3.7
      mm. Lesions located on the forehead (1.26 +/- 0.44 mm) and on the medial face
      (1.23 +/- 0.65 mm), were deeper than lesions on the trunk and extremities. PWS
      involving areas that respond poorly to treatment were on average 0.14 mm deeper
      than PWS involving areas that responded well. The depth of the PWS, as determined
      with high-resolution ultrasound, seems to correlate only to some degree with the
      response to pulsed dye laser treatment. Since this treatment, with its
      superficial penetration, cannot reach the deeper vessels of a PWS, skin
      ultrasound could be a good complement in the prognostic investigation as well as
      for planning treatment.

PMID- 10954212
TI  - Paraneoplastic skin manifestations of lung cancer.
AB  - Two cases are reported illustrating a parallel course of extensive skin
      manifestations and lung cancer. The cases presented features of paraneoplastic
      acrokeratosis (Bazex's syndrome) and erythema gyratum repens though they did not
      completely correspond to these well-defined conditions. In both cases the
      cutaneous eruption appeared more than a year prior to the diagnosis of lung
      cancer, and the skin disease resolved completely within half a year following
      surgical removal of the cancer. The need is stressed for repeated cancer screens
      when a cutaneous marker of internal malignancy is suspected.

PMID- 10954213
TI  - Thermal effects of emollients on facial skin in the cold.
AB  - Ointments are traditionally used in Finland for protection against facial
      frostbite. Recent epidemiological reports showed unexpectedly, however, that the
      use of ointments is a statistically considerable risk factor for frostbite of the
      face and ears. The effects of 4 different emollients on facial temperature were
      studied in 46 acute cold exposures. The voluntary test persons sat in a cold
      chamber after emollients were applied thickly on half of the face, while the
      other half acted as an untreated control. Thermistors and an infrared scanner
      were used to measure skin temperature of symmetrical areas of the face. The
      thermal sensations on the corresponding sites were also recorded. Test emollients
      more often had an objectively cooling than a warming effect on facial skin.
      However, white petrolatum often produced a subjectively warming skin sensation.
      "Protective" ointments may cause a false sensation of safety, leading to
      increased risk of frostbite due to neglect of other protective measures.

PMID- 10954214
TI  - Localized pustular psoriasis with onycholysis representing a Kobner phenomenon.

PMID- 10954215
TI  - Comel-Netherton syndrome: evolution of manifestation in a 20-year follow-up and
      phenotypic overlap with peeling skin syndrome type B.

PMID- 10954216
TI  - Drug eruption due to low molecular weight heparin.

PMID- 10954217
TI  - Linear lichen planopilaris of the face treated with low-dose cyclosporin A.

PMID- 10954218
TI  - Rare case of Cockayne syndrome with xeroderma pigmentosum.

PMID- 10954219
TI  - Congenital triangular alopecia in phakomatosis pigmentovascularis: report of 3
      cases.

PMID- 10954220
TI  - Immunotherapy with diphenylcyclopropenone of recalcitrant warts: a retrospective
      analysis.

PMID- 10954221
TI  - Classic Kaposi's sarcoma and vascular endothelial growth factor.

PMID- 10954222
TI  - Pemphigus vulgaris possibly triggered by Cilazapril.

PMID- 10954223
TI  - UVA1 for hypereosinophilic syndrome.

PMID- 10954224
TI  - Atypical erythema multiforme occurring at the early phase of Lyme disease?

PMID- 10954225
TI  - Dermatoscopic diagnosis of malignant melanoma.

PMID- 10954226
TI  - Acute generalized exanthematous pustulosis induced by dextropropoxyphene and
      confirmed by patch testing.

PMID- 10954227
TI  - The effectiveness of low-dose intravenous immunoglobulin in chronic urticaria.

PMID- 10954228
TI  - Botulinum toxin A for focal hyperhidrosis in leg amputees: a case report.

PMID- 10954229
TI  - Basal cell carcinoma arising in a localized linear verrucous epidermal naevus.

PMID- 10954230
TI  - Improvement of cold urticaria by treatment with the leukotriene receptor
      antagonist montelukast.

PMID- 10954231
TI  - Lipoid proteinosis: high-resolution two-dimensional protein electrophoresis of
      affected and non-affected skin.

PMID- 10954232
TI  - Gelatin-induced urticaria and anaphylaxis after tick-borne encephalitis vaccine.

PMID- 10954233
TI  - Epiluminescence microscopy in cutaneous larva migrans.

PMID- 10954234
TI  - Plasmacytosis: systemic or cutaneous, are they distinct?

PMID- 10954235
TI  - Syphilitic chancre despite use of condoms: "condom chancre".

PMID- 10954236
TI  - Subungual myiasis.

PMID- 10954237
TI  - A familial case of scleroderma en coup de sabre.

PMID- 10954238
TI  - Long-term outcome of epilepsy.
AB  - Few prospective, population-based, long-term follow-up studies exist on people
      with epilepsy. Still fewer reports cover social outcome. Overall mortality is two
      to three times higher than expected. The contribution of epilepsy is variable.
      Importantly, the type of epilepsy syndrome and gender must be considered in the
      estimation of mortality rates in epilepsy. Sudden unexpected death and its
      mechanisms also need further consideration. Approximately. two thirds of
      surviving patients will be in terminal remission twenty years after onset of
      epilepsy and half of them are seizure-free without medication. The best
      independent predictors of remission are absence of organic brain damage, low
      intensity seizure propensity and good early effect of drug therapy. The long-term
      outcome is often predictable by observation of the early outcome of seizures. One
      third of children with epilepsy are mentally retarded. Poor social outcome is
      related to associated neurological disabilities, drug resistant seizures and
      polytherapy. However, even patients with uncomplicated epilepsy, idiopathic
      etiology and terminal remission without medication do less favourably than their
      matched controls in basic and vocational education, and reproductive activity.
      The employability of this subgroup, however, does not differ significantly from
      that of controls, compared with approximately 60% of all people with epilepsy.
      Further research is needed particularly to enable a better determination of
      predictors of long-term outcome, recurrence of seizures after drug withdrawal and
      the role of drug therapy in long-term prognosis.

PMID- 10954239
TI  - Cardiac asystole in partial seizures.
AB  - Literature review shows many anecdotal case reports of cardiac asystole in ictal
      recordings of partial seizures. We have reviewed our data from the last five
      years, of patients who are being assessed for epilepsy surgery and found 2 out of
      more than 1,500 complex partial seizures, recorded in 589 consecutive patients,
      showing a significant period of asystole (13 and 15 seconds). Our previous
      studies of cardiac and respiratory parameters during partial seizures showed that
      a central apnoea occurred in 39%. It is probable that sudden death during
      seizures is due to the interaction of both cardiac and respiratory
      irregularities. Although rare (occurrence < 0.15%), the possibility of cardiac
      asystole occurring in an epilepsy monitoring unit highlights the need for
      resuscitation equipment to be readily available and for trained nursing staff.
      Furthermore, it is important to recognize that the semiology of seizures may be
      affected by the consequences of secondary cardiac asystole.

PMID- 10954240
TI  - Eating epilepsy. Heterogeneity of ictal semiology: the role of video-EEG
      monitoring.
AB  - In this paper, three more cases of eating-induced seizures are reported. We have
      obtained ictal video-electroencephalogram (EEG) recordings for two patients,
      which confirm the heterogeneity of ictal semiology of these seizures. However, in
      all the cases the inclusion of this kind of reflex epilepsy (RE) among the
      localization-related epilepsies (LRE) is confirmed. The usefulness of video EEG
      monitoring in studying these seizures and reflex epilepsy in general (RE) is
      stressed.

PMID- 10954242
TI  - Continuous spikes and waves during slow sleep (CSWS): outcome in adulthood.
AB  - We report a longitudinal, electroencephalographic and neuropsychological analysis
      of epilepsy with continuous spikes and waves during slow sleep (CSWS) in a 19
      year-old boy. The clinical course fluctuated, with temporary worsening or
      improvement of the paroxysmal abnormalities, epilepsy and cognitive functions. At
      the end of the follow-up period, seizures persisted. Evaluation of the boy's
      behaviour, language and cognitive function suggested a dysexecutive syndrome. We
      discuss the relationship between paroxysmal abnormalities and neuropsychological
      disorders.

PMID- 10954241
TI  - Piracetam and levetiracetam: close structural similarities but different
      pharmacological and clinical profiles.
AB  - Piracetam (PIR) and levetiracetam (LEV), an S-enantiomer, are pyrrolidone
      derivatives that share similar chemical structures but have distinct
      pharmacological profiles and consequently different clinical uses. Although the
      mode of action of neither drug has been fully elucidated, they do not interact
      with inhibitory or excitatory neurotransmission or alter membrane excitability. A
      brain-specific stereoselective binding site has been identified for which LEV and
      other S-enantiomers, but not PIR, have high affinity. In preclinical studies, PIR
      significantly improves learning and memory; in contrast, LEV has less effect but
      is much more active in preventing seizures. Both drugs have a high therapeutic
      index and are well tolerated. PIR, a nootropic drug, is used in the therapy of
      age-related cognitive disturbances and poststroke aphasia. Clinical experience
      has also shown that at high doses it is effective against cortical myoclonus. LEV
      is an antiepileptic drug. Clinical trials have confirmed its efficacy in partial
      seizures and preliminary findings suggest that it is also effective in
      generalized seizures and myoclonus.

PMID- 10954243
TI  - The role of gamma knife surgery in the treatment of severe epilepsies.
AB  - There is a strong rationale for investigation of the role of gamma knife
      radiosurgery in the treatment of medically intractable epilepsy. To explore this
      potential application, the current outcome and morbidity associated with
      established microsurgical treatment, as well as the associated advantages and
      disadvantages of open surgery, are reviewed. The preliminary evidence in support
      of radiosurgical treatment and the recent experience with gamma knife treatment
      for epilepsy associated with mesial temporal sclerosis, cavernous angioma, and
      hypothalamic hamartoma or other lesions are presented. The strengths and
      limitations of this application are discussed, and the challenges facing both
      microsurgical and radiosurgical approaches are considered. Gamma knife surgery
      can be a main approach among others in the armamentarium of epilepsy surgery.
      Although the benefits of comfort and reduced invasivity can be clearly perceived,
      larger series and long-term follow up are still required in order to evaluate the
      future of this particular surgical approach.

PMID- 10954245
TI  - Rotatory seizures are not as rare as described.

PMID- 10954244
TI  - Encephalopathy with epileptic spasms resolved with corticoids in a 69 year-old
      patient.
AB  - A 69 year-old man with a history of recent temporal lobe seizures, presented with
      progressive coma and frequent epileptic spasms. Ictal EEG, PET and SPECT
      alterations were strikingly similar to those described in infantile spasms.
      Conventional antiepileptic drugs were ineffective but the introduction of
      corticoids induced a dramatic improvement with disappearance of the spasms. The
      etiology remains unknown. Epileptic spasms may occur in the elderly. If
      conventional antiepileptic drugs are ineffective, corticoids should be tried
      immediately.

PMID- 10954246
TI  - Introduction: the history of the Alpha One International Registry (A.I.R.).

PMID- 10954247
TI  - Loop-sheet polymerization: the mechanism of alpha1-antitrypsin deficiency.
AB  - Alpha1-antitrypsin deficiency results from point mutations that distort the
      structure of the protein to allow a unique protein-protein interaction that we
      have termed loop-sheet polymerization. Polymers of Z alpha1-antitrypsin
      accumulate within hepatocytes to form inclusion bodies that are associated with
      juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein
      predisposes the Z alpha1-antitrypsin homozygote to emphysema. This polymerization
      process also occurs in variants of other members of the serine proteinase
      inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha1
      antichymotrypsin in association with thrombosis, angiooedema and chronic
      obstructive pulmonary disease respectively, and we have recently shown that it
      underlies a novel inclusion body dementia. Understanding this mechanism of
      polymerization allows rational drug design to block the protein-protein linkage
      and so ameliorate the associated disease.

PMID- 10954248
TI  - Molecular mechanisms of alpha1-antitrypsin null alleles.
AB  - Alpha1-antitrypsin (alpha1-AT) is the most abundant circulating inhibitor of
      serine proteases and therefore is essential to normal protease-anti-protease
      homeostasis. Inheritance of two parental alpha1-AT deficiency alleles is
      associated with a substantially increased risk for development of emphysema and
      liver disease. In very rare circumstances individuals may inherit alpha1-AT null
      alleles. Null alpha1-AT alleles are characterized by the total absence of serum
      alpha1-AT. These alleles represent the extreme end in a continuum of alleles
      associated with alpha1-AT deficiency. The molecular mechanisms responsible for
      absence of serum alpha1-AT include splicing abnormalities, deletion of alpha1-AT
      coding exons and premature stop codons. While these alleles comprise only a small
      proportion of alpha1-AT alleles associated with profound alpha1-AT deficiency,
      studies of their molecular mechanisms provide valuable insights into the
      structure, gene expression and intracellular transport of alpha1-AT.

PMID- 10954249
TI  - Alpha1-antitrypsin deficiency: epidemiology and prevalence.

PMID- 10954250
TI  - Screening for alpha1-Pi deficiency in patients with lung diseases.

PMID- 10954251
TI  - Alpha1-antitrypsin deficiency: incidence and detection program.
AB  - Most individuals with AAT deficiency have escaped detection by healthcare systems
      worldwide. The large number of undiagnosed individuals has made it difficult to
      define the natural history of the clinical disease accurately, and severe
      ascertainment bias has colored the clinical descriptions of the disease. Most
      importantly, undetected individuals lose opportunities for important lifestyle
      changes and preventive therapies. To address this problem, the World Health
      Organization has recommended that all patients with chronic obstructive lung
      disease, and all adults and adolescents with asthma, be tested for AAT
      deficiency. Historically, the AAT Deficiency Detection Center has tested more
      than 30 000 individuals for the disease, and we have identified more than 1000
      cases of AAT deficiency (approximately 30% of the known cases in the United
      States). Currently, we are implementing methods for determining AAT concentration
      (level), phenotype, and genotype in specimens of whole blood dried onto filter
      paper. This full spectrum of robust tests is performed on samples that are easily
      obtained and shipped to a central laboratory for processing. Wide application of
      these procedures may help to bring large numbers of presently undiagnosed
      patients to medical attention.

PMID- 10954252
TI  - The long-term impact of oral contraceptives on ovarian and endometrial
      carcinogenesis.

PMID- 10954253
TI  - Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for
      breast and ovarian cancer.
AB  - The hereditary breast (BC) and ovarian (OC) cancer syndrome (HBOC) includes
      genetic alterations of various susceptibility genes such as TP53, ATM, PTEN or
      MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6, BRCA1 and BRCA2. Germline mutations of the
      cancer-susceptibility genes BRCA1 and BRCA2 seem to be the major aetiology of the
      HBOC. Genetic counselling and identification of high-risk families may be
      essential (1) to provide the best method for genetic testing by explaining the
      sensitivity and specificity of the methods, (2) to offer the opportunity to
      participate in specific early cancer detection programmes (breast (self)
      palpation, ultrasound, mammography and magnetic resonance tomography for breast
      cancer; vaginal exploration and ultrasound for ovarian cancer), (3) to inform
      them about prophylactic medication (oral contraceptive pill (OCP),
      chemoprevention (tamoxifen, raloxifen, aromatase inhibitors)) or surgery
      (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide
      individualized psychological support. To fulfil these broad demands, an inter
      disciplinary counselling approach (gynaecological oncology, human genetics,
      molecular biology, psychotherapy) in the setting of a cancer genetic clinic seems
      the most appropriate. There, participation in predictive genetic testing or the
      use of preventive or therapeutic options may be discussed extensively with the
      subjects. In particular, preventive options are emotionally disturbing for the
      subjects, and in cases of previous cancer. BC chemoprevention for high-risk women
      does not seem to be as effective as expected. However, OCP reduces the risk for
      OC. For prophylactic surgery, various points have to be considered, including:
      (1) individual risk assessment and gain in life expectancy, (2) value of
      screening and early detection methods or medical prevention, (3) disease
      characteristics and prognosis, and (4) anxiety and quality of life. Decisions
      regarding these options have to be individualized and psychological support must
      be offered during the period of decision and follow-up.

PMID- 10954255
TI  - Fatty acids, biliary bile acids, lipid peroxidation products and gallbladder
      carcinogenesis.
AB  - Secondary bile acids, by virtue of their lipophilic action, change the membrane
      composition of hepatocyte mitochondria, the inner membranes of which harbour the
      cytochrome P450 oxido-reductase system. The changes in the membrane fatty acid
      composition decreases the activity of the mitochondrial enzyme system, thereby
      making them incapable of handling free radicals generated during the normal
      process of energy production and detoxification. These free radicals in turn may
      attack membrane polyunsaturated fatty acids to initiate and propagate lipid
      peroxidation, leading to formation of aldehydic lipid peroxidation products.
      Notably among these is 4-hydroxynonenal, which has a high genotoxic and
      neoplastic potential. Disorders of gallbladder contractility further lead to
      accumulation of these toxic substances normally excreted in bile, and if retained
      for long time in the gallbladder they may induce gallbladder carcinogenesis.

PMID- 10954254
TI  - Systematic review of epidemiological studies on meat, dairy products and egg
      consumption and risk of colorectal adenomas.
AB  - In view of the direct contact between food residues and metabolites and the large
      bowel mucosa, it might be expected that food consumption patterns would affect
      the risk of colorectal carcinogenesis. Many lines of evidence support the adenoma
      carcinoma sequence as the major mechanism of colorectal carcinogenesis. The
      present study aimed to investigate the role of foods of animal origin such as
      meat, dairy products and eggs in the early stages of colorectal carcinogenesis.
      Eleven case-control and two cohort studies on colorectal polyps and meat, dairy
      products and eggs were identified. A quantitative review of these studies and a
      meta-analysis were carried out. The combined odds ratios suggest a positive
      association between the risk of colorectal polyps and beef consumption and a
      negative association with fish or combined poultry/fish consumption. An increase
      in the ratio of the consumption of red meat to consumption of fish/chicken was
      associated with an increase in the colorectal polyp risk. Neither dairy product
      nor egg consumption had a substantial effect on the development of colorectal
      polyps. These results suggest that dietary factors associated with polyp
      development may be not the same as those associated with cancer.

PMID- 10954256
TI  - Lifestyle factors and insulin-like growth factor 1 levels among elderly men.
AB  - Insulin-like growth factor 1 (IGF-1) is a potentially important determinant of
      disease; hence epidemiological identification of factors that influence
      circulating IGF-1 is merited. We therefore analysed data collected in Greece to
      determine the relationship between anthropometric, lifestyle and dietary
      variables and serum levels of IGF-1 among elderly men. We identified 51 men with
      prostate cancer, 50 men with benign prostatic hyperplasia, and 52 apparently
      healthy elderly men (controls), all matched for age (+/- 1 year). These 153 men
      provided blood specimens and were interviewed using a validated lifestyle and
      food frequency questionnaire. We performed multivariate linear regression to
      identify potential predictors of circulating IGF-1. After controlling for age,
      body mass index, smoking habits, alcohol drinking and coffee consumption, each 5
      cm increase in height predicted a 13.0% increase in IGF-1 (95% CI 0.4-27.2%)
      among the controls and a 11.3% increase in IGF-1 (95% CI 4.5-18.6%) among the
      entire study group. None of the investigated dietary factors (total fat,
      carbohydrate, protein, dairy products, tomatoes, calcium) were strongly related
      to IGF-1 levels. The positive association between IGF-1 and height integrates the
      empirical evidence linking IGF-1 and height with prostate cancer risk.

PMID- 10954257
TI  - An age, period and cohort analysis of pleural cancer mortality in Europe.
AB  - Death certification data from pleural cancer in eight European countries
      providing data to the World Health Organization database over the period 1970
      1994 were analysed using a log-linear Poisson model to disentangle the effects of
      age, birth cohort and period of death. The age effect reached values between 10
      and 15/100,000 males at age 80-84 in most countries, except Hungary (6.7),
      Switzerland (18.0), France (20.6) and the Netherlands (36.5). Cohort effects were
      steadily and appreciably upwards in all countries up to the generations born in
      1940 or 1945, and levelled off for the 1950 cohort, except in Hungary, where
      persistent rises were observed. Thus, most rises in pleural cancer mortality in
      Europe were on a cohort of birth basis. Since most pleural cases were asbestos
      related mesotheliomas, and since asbestos has an early-stage effect on subsequent
      mesothelioma risk, exposure early in life is important for determining the
      subsequent mesothelioma risk of each generation. Consequently, the data indicate
      that the peak mortality from pleural cancer in most western European countries
      will be reached in the first decades of the 21st century, i.e. around 2010-2020,
      when the generations born between 1940 and 1950 will reach the peak age for
      mesothelioma incidence and mortality. This contrasts with US data, where the peak
      of pleural cancer incidence has been reached at the end of the 20th century, and
      reflects a delay in adopting adequate prevention measures since the 1940-1945
      generations entered the workforce in the 1960s, when cancer risk from asbestos
      exposure was already recognized.

PMID- 10954258
TI  - H2-receptor antagonists may increase the risk of cardio-oesophageal
      adenocarcinoma: a case-control study.
AB  - Adenocarcinoma of the lower oesophagus and the gastric cardia has shown a
      dramatic worldwide increase in incidence over the last 25 years, but the cause is
      unknown. A large number of drugs have been introduced over this period of time,
      and it has been suggested that drugs that relax the lower oesophageal sphincter
      (DRLOS) might be causative, and on the other hand that non-steroidal anti
      inflammatory drugs (NSAIDS) may be protective. H2-receptor antagonists (H2RAs)
      may allow achlorhydric reflux to continue without symptoms, and it is postulated
      that such asymptomatic reflux is uncontrolled by the usual conservative measures
      and may lead to increased oesophageal damage. H2RAs were first marketed in 1970
      and might be the cause of the observed increase of cardio-oesophageal
      adenocarcinoma (COA). In a case-control study, the records of 56 subjects who
      died of COA in the period 1 January 1990 to 31 December 1992 were compared with
      those of 56 age-/sex-matched controls who died of myocardial infarction. They
      were 28 females and 84 males, mean age 69.8 years. The NHS records containing the
      lifetime prescription history of each subject were retrieved from the health
      authority. Each prescription was recorded, omitting drugs taken in the two years
      before diagnosis. Analysis was performed using conditional logistic regression.
      Other variables, including the use of antacids, steroids, smoking and alcohol,
      were also examined. Subjects dying of COA were more likely to have consumed H2RAs
      (relative risk (RR) 7.50, 95% CI 1.33-42.09, P < 0.02). On the other hand, they
      were less likely to have consumed NSAIDs (RR 0.16, 95% CI 0.03-0.93, P < 0.04) or
      DRLOS (RR 0.14, 95% CI 0.02-1.0, P = 0.05). This study supports a protective
      effect from NSAIDs against COA, but the similar effect of DRLOS is related to the
      increased use of cardiac drugs in the control group. H2RAs appear to have a
      harmful effect, which may be related to the worldwide increase in COA. However,
      the trend may have been apparent before cimetidine was widely available, and it
      is possible that the cause is multi-factorial.

PMID- 10954259
TI  - Smoking and colorectal adenomas: a case-control study.
AB  - A positive association between tobacco and colorectal adenomas has been
      suggested. Smoking is, however, also associated with 'poor' dietary habits, which
      in turn may be related to risk of adenomas. It is therefore of interest to study
      the relationship between smoking, diet and risk of colorectal adenomas in follow
      up studies. We compared 87 adenoma cases to 35 'hospital' and 35 healthy controls
      (all controls were age- and sex-matched and proven to be free of adenomas).
      Smoking data were collected by an interview and a self-administrated
      questionnaire with a time interval of at least one month. After 3 years of follow
      up, all polyps were removed. Our data indicate that smoking is associated with
      adenoma prevalence, but not necessarily with size, multiplicity, growth or
      recurrence of adenomas. Compared to both sets of controls, cases reported to have
      smoked more than 15 pack-years, or who are current smokers, had a fourfold
      increased frequency of adenomas (odds ratios 3.6-5.9). Smokers with adenomas had
      dietary habits that may also be associated with adenomas. The smoking estimates
      remained largely unchanged even after adjustments for dietary variables in
      multivariate analysis. This study lends support to the theory of an initiating
      role of tobacco smoke in neoplasia formation.

PMID- 10954260
TI  - Comparisons of the anti-proliferative effects of butyrate and aspirin on human
      colonic mucosa in vitro.
AB  - The short-chain fatty acid butyrate is regarded as a regulative agent in
      haemostasis of mucosal cell turnover. Inhibition of prostaglandin E2 synthesis is
      particularly involved in this regulation process. In the present study,
      proliferation was stimulated in colonic biopsies of 12 healthy subjects (age 51.3
      years, range 25-81) by incubation with deoxycholic acid (5 micromol/l DCA). The
      anti-proliferative and cyclo-oxygenase-inhibiting properties of butyrate (10
      mmol/l BUT) and of aspirin (555 micromol/l ASA) were investigated. Colonic cell
      proliferation was determined by bromodeoxyuridine immunohistochemistry. PGE2
      release into the incubation medium was measured by radioimmunoassay. Incubation
      with DCA/ASA, DCA/BUT and DCA/ASA/BUT revealed a significant reduction in crypt
      cell proliferation as measured by the labelling index of the whole crypt in
      comparison to incubation with DCA alone (DCA/ASA: 0.14, P < 0.01; DCA/BUT: 0.15,
      P < 0.05; DCA/ASA/BUT: 0.15, P < 0.05, versus DCA: 0.18). The labelling index for
      the upper 40% of the crypt was only lower after incubation with DCA/ASA (0.023)
      compared to DCA (0.028) (P < 0.05). PGE2 release from biopsy specimens was only
      significantly decreased in the incubation media where ASA was added (DCA/ASA:
      29.0 pg/mg mucosa/h, P < 0.005; DCA/ASA/BUT: 31.4 pg/mg mucosa/h, P < 0.01 versus
      DCA: 56.9 pg/mg mucosa/h). Butyrate and aspirin showed no synergistic effects.
      The results indicate a normalization of DCA-induced hyperproliferation of colonic
      mucosa by butyrate, and, even more efficiently, by aspirin. The data support the
      hypothesis that butyrate and aspirin can act as chemopreventive agents in colon
      carcinogenesis.

PMID- 10954261
TI  - WHO consensus conference on diet and cancer. Members of the breast cancer panel.

PMID- 10954262
TI  - Tick tock, doc: the rapid evaluation of acute stroke to direct therapy and
      improve patient outcome.

PMID- 10954263
TI  - Bleed or stroke? Diffusion measurements in intracranial hematomas.

PMID- 10954264
TI  - Diffusion-weighted imaging of the spinal cord: is there a future?

PMID- 10954265
TI  - Redefining "normal".

PMID- 10954266
TI  - Feasibility and practicality of MR imaging of stroke in the management of
      hyperacute cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Neuroimaging techniques such as diffusion- and perfusion
      weighted MR imaging have been proposed as tools for advanced diagnosis in
      hyperacute ischemic stroke. There is, however, substantial doubt regarding the
      feasibility and practicality of applying MR imaging for the diagnosis of stroke
      on a routine basis, especially with respect to possible delay for specific
      treatment such as thrombolysis. In this study, we tested whether MR imaging of
      stroke is safe, fast, and accurate, and whether the gain in additional
      information can be used in the daily routine without a loss of time and a risk of
      suboptimal treatment for the patient with stroke. METHODS: Between September 1997
      and August 1999, 64 patients with acute ischemic stroke were recruited for MR
      imaging (ie, diffusion-weighted imaging, perfusion-weighted imaging, MR
      angiography, T2-weighted imaging) after a baseline CT was performed. We evaluated
      practicality and feasibility of MR imaging of stroke by analyzing the intervals
      between symptom onset, arrival, CT, and MR imaging. RESULTS: Sixty-four patients
      (mean age, 60.9 years) underwent routine CT and MR imaging within 12 hours after
      stroke onset (n=25, < or =3 hr; n=26, 3-6 hr; n=13, 6-12 hr). Median times to
      arrival, start of CT, MR imaging, and between CT and MR imaging were 1.625 hours,
      2 hours, 3.875 hours, and 1 hour, respectively. Intervals between symptom onset
      and MR imaging (P<.005), arrival and MR imaging (P<.002), and CT and MR imaging
      (P=.0007) differed significantly between the early phase of the study and after
      November 1998, whereas the intervals between symptom onset and arrival, symptom
      onset and CT, and arrival and CT did not. Hemorrhage could be excluded in all; a
      perfusion/diffusion match or mismatch could be shown in 63 of 64 patients.
      CONCLUSION: Practice and experience with MR imaging in a stroke team
      significantly reduce the time and effort required to perform this technique and
      thus make 24-hour availability for MR imaging of stroke practical. Assessment of
      patients with hyperacute stroke is rapid and comprehensive. Image quality can be
      substantially improved by head immobilization and by mild sedation, if necessary.

PMID- 10954267
TI  - Diffusion measurements in intracranial hematomas: implications for MR imaging of
      acute stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of our study was to analyze the diffusion
      properties of intracranial hematomas to understand the effects of hematomas on
      diffusion-weighted MR images of patients with acute stroke and to further our
      understanding of the evolution of signal intensities of hematomas on conventional
      MR images. We hypothesized that hematomas containing blood with intact RBC
      membranes (ie, early hematomas) have restricted diffusion compared with hematomas
      in which RBC membranes have lysed. METHODS: Seventeen proven intracranial
      hematomas were studied with conventional and diffusion MR imaging. Hematomas were
      characterized using conventional images to determine the stage of evolution and
      their putative biophysical composition, as described in the literature. Apparent
      diffusion coefficient (ADC) measurements for each putative hematoma constituent
      (intracellular oxyhemoglobin, intracellular deoxyhemoglobin, intracellular
      methemoglobin, and extracellular methemoglobin) were compared with each other and
      with normal white matter. RESULTS: Hematomas showing hemoglobin within intact
      RBCs by conventional MR criteria (n = 14) showed equivalent ADC values, which
      were reduced compared with hematomas containing lysed RBCs (P = .0029 to .024).
      Compared with white matter, hematomas containing lysed RBCs had higher ADC
      measurements (P = .003), whereas hematomas containing intact RBCs had reduced ADC
      measurements (P < .0001). CONCLUSION: Restricted diffusion is present in early
      intracranial hematomas in comparison with both late hematomas and normal white
      matter. Therefore, early hematomas would be displayed as identical to the signal
      intensity of acute infarction on ADC maps, despite obvious differences on
      conventional MR images. These data also are consistent with the biochemical
      composition that has been theorized in the stages of evolving intracranial
      hematomas and provide further evidence that paramagnetic effects, rather than
      restriction of water movement, are the dominant cause for their different
      intensity patterns on conventional MR images.

PMID- 10954268
TI  - A standardized method of generating time-to-peak perfusion maps in dynamic
      susceptibility contrast-enhanced MR imaging.
AB  - BACKGROUND AND PURPOSE: Perfusion MR imaging, performed as dynamic-susceptibility
      contrast-enhanced MR imaging, is sensitive to hemodynamic risks for patients with
      cerebrovascular disease. We sought to define a quantitative parameter for
      perfusion MR imaging, which shows brain areas at hemodynamic risk and enables
      direct comparison of different perfusion MR imaging examinations. METHODS: A new
      standardization procedure for the time-to-peak (TTP) parameter, standardized time
      to peak (stdTTP), was introduced. The stdTTP automatically calculates a time
      offset correlated to the earliest enhancing voxels in a section and rescales all
      TTP values accordingly. Because of a close relation between this offset and
      stdTTP of early enhancing voxels in central vascular territories (CVTs), stdTTP
      provides an estimate of the bolus run time between CVTs and related border zones
      (BZs). The stdTTP in CVTs and BZs was measured in 11 patients without hemodynamic
      impairment by using high temporal resolution dynamic-susceptibility contrast
      enhanced perfusion MR imaging. RESULTS: An excellent comparability of different
      dynamic susceptibility contrast-enhanced MR imaging studies was found. The stdTTP
      in CVTs was 0.4 +/- 0.5 s (minimum, 0 s; maximum, 1.3 s) for the anterior, 0.5 +/
      0.3 s (minimum, 0 s; maximum, 1.0 s) for the middle, and 1.4 +/- 0.5 s (minimum,
      0.4 s; maximum, 2.4 s) for the posterior cerebral artery. In the anterior BZ,
      stdTTP was 2.3 +/- 0.4 s (minimum, 1.6 s; maximum, 3.2 s), and in the posterior
      BZ, stdTTP was 2.8 +/- 0.4 s (minimum, 2.0 s; maximum, 3.4 s). CONCLUSION: The
      results suggest a limit for stdTTP of approximately 3.5 s in the anterior and
      posterior BZs. The stdTTP could serve as a quantitative measure for the
      hemodynamic risk assessment of patients with cerebrovascular disease. Because
      stdTTP can be directly derived from the measured curves, the hemodynamic
      situation of a patient can be judged with a minimum of computational effort.

PMID- 10954269
TI  - Posterior reversible encephalopathy syndrome: utility of fluid-attenuated
      inversion recovery MR imaging in the detection of cortical and subcortical
      lesions.
AB  - BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is
      typically characterized by headache, altered mental functioning, seizures, and
      visual loss associated with imaging findings of bilateral subcortical and
      cortical edema with a predominantly posterior distribution. Our goal was to
      determine whether fluid-attenuated inversion recovery (FLAIR) imaging improves
      the ability to detect subtle peripheral lesions of PRES, as compared with
      conventional MR techniques. METHODS: Sixteen patients with clinical and imaging
      findings consistent with PRES were studied. Thirteen patients had undergone
      transplantation and had cyclosporin A neurotoxicity. Fast-FLAIR images were
      compared with spin-echo proton density- and T2-weighted images. RESULTS: FLAIR
      imaging improved diagnostic confidence and conspicuity of the T2 hyperintense
      lesions of PRES, typically in the subcortical white matter of the
      parietooccipital regions bilaterally. On all 23 abnormal MR studies, FLAIR was
      judged superior to proton density- and T2-weighted images for the detection of
      PRES in the supratentorial brain. In a mean of 6.7 of 23 studies, FLAIR findings
      prompted a raise in the grade of disease severity. FLAIR also showed cortical
      involvement in 94% of patients with PRES and in a mean of 46% of the total lesion
      burden. In four cases, subtle lesions were virtually undetectable without FLAIR.
      Brain stem or cerebellar disease was encountered in 56% of patients. CONCLUSION:
      FLAIR improves the ability to diagnose and detect subcortical and cortical
      lesions in PRES as compared with proton density- and T2-weighted spin-echo
      images. We therefore believe that FLAIR should be performed in patients with
      suspected PRES to allow more confident recognition of the often subtle imaging
      abnormalities.

PMID- 10954270
TI  - Assessment of blood flow velocity and diameter of the middle cerebral artery
      during the acetazolamide provocation test by use of transcranial Doppler
      sonography and MR imaging.
AB  - BACKGROUND AND PURPOSE: Our purpose was to show changes in the diameter of the M1
      segment of the middle cerebral artery (MCA) by using high-resolution MR imaging
      in patients with chronic internal carotid artery occlusion after IV administered
      acetazolamide challenge. Changes in blood flow velocity of the basal cerebral
      arteries are thought to correlate with changes of cerebral blood flow. Changes in
      the diameter of the basal cerebral arteries, however, might influence the
      validity of transcranial Doppler measurements. METHODS: Eight patients with
      internal carotid artery occlusion who were undergoing acetazolamide testing for
      assessment of cerebrovascular vasomotor reactivity were included in the study.
      Blood flow velocities of both MCAs were measured with transcranial Doppler
      sonography before and 25 minutes after the administration of acetazolamide.
      Before and 15 minutes after the administration of medication, MR imaging was
      performed contralateral to the occlusion side. A T2-weighted turbo-gradient spin
      echo sequence was chosen to show a cross section of the M1 segment in high
      resolution (pixels, 0.27 x 0.29 mm). Based on interpolated data, the smallest and
      greatest MCA diameters were determined. RESULTS: We did not find changes in the
      diameter of the MCA after acetazolamide provocation testing with high-resolution
      MR imaging in patients with occlusive extracranial carotid artery disease.
      CONCLUSION: The results of our study support the hypothesis that changes in MCA
      flow velocity measured by transcranial Doppler sonography reflect relative
      changes in cerebral blood flow after acetazolamide provocation testing.

PMID- 10954271
TI  - Discrimination between neoplastic and nonneoplastic brain lesions by use of
      proton MR spectroscopy: the limits of accuracy with a logistic regression model.
AB  - BACKGROUND AND PURPOSE: The most accurate method of clinical MR spectroscopy
      (MRS) interpretation remains an open question. We sought to construct a logistic
      regression (LR) pattern recognition model for the discrimination of neoplastic
      from nonneoplastic brain lesions with MR imaging-guided single-voxel proton MRS
      data. We compared the LR sensitivity, specificity, and receiver operator
      characteristic (ROC) curve area (Az) with the sensitivity and specificity of
      blinded and unblinded qualitative MRS interpretations and a choline (Cho)/N
      acetylaspartate (NAA) amplitude ratio criterion. METHODS: Consecutive patients
      with suspected brain neoplasms or recurrent neoplasia referred for MRS were
      enrolled once final diagnoses were established by histopathologic examination or
      serial neurologic examinations, laboratory data, and imaging studies. Control
      spectra from healthy adult volunteers were included. An LR model was constructed
      with 10 input variables, including seven metabolite resonance amplitudes,
      unsuppressed brain water content, water line width, and the final diagnosis
      (neoplasm versus nonneoplasm). The LR model output was the probability of tumor,
      for which a cutoff value was chosen to obtain comparable sensitivity and
      specificity. The LR sensitivity and specificity were compared with those of
      qualitative blinded interpretations from two readers (designated A and B),
      qualitative unblinded interpretations (in aggregate) from a group of five staff
      neuroradiologists and a spectroscopist, and a quantitative Cho/NAA amplitude
      ratio > 1 threshold for tumor. Sensitivities and specificities for each method
      were compared with McNemar's chi square analysis for binary tests and matched
      data with a significance level of 5%. ROC analyses were performed where possible,
      and Az values were compared with Metz's method (CORROC2) with a 5% significance
      level. RESULTS: Of the 99 cases enrolled, 86 had neoplasms and 13 had
      nonneoplastic diagnoses. The discrimination of neoplastic from control spectra
      was trivial with the LR, reflecting high homogeneity among the control spectra.
      An LR cutoff probability for tumor of 0.8 yielded a specificity of 87%, a
      comparable sensitivity of 85%, and an area under the ROC curve of 0.96.
      Sensitivities, specificities, and ROC areas (where available) for the other
      methods were, on average, 82%, 74%, and 0.82, respectively, for readers A and B,
      89% (sensitivity) and 92% (specificity) for the group of unblinded readers, and
      79% (sensitivity), 77% (specificity), and 0.84 (Az) for the Cho/NAA > 1
      criterion. McNemar's analysis yielded significant differences in sensitivity (n
      approximately 86 neoplasms) between the LR and reader A, and between the LR and
      the Cho/NAA > 1 criterion. The differences in specificity between the LR and all
      other methods were not significant (n approximately 13 nonneoplasms). Metz's
      analysis revealed a significant difference in Az between the LR and the Cho/NAA
      ratio criterion.

PMID- 10954272
TI  - Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques:
      absolute metabolic values over 2 years during a clinical pharmacological study.
AB  - BACKGROUND AND PURPOSE: The time courses of total creatine (Cr), N
      acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been
      investigated in the follow-up of contrast-enhancing multiple sclerosis (MS)
      plaques. Therefore, over a period of 2 years, we compared the absolute
      concentrations of these metabolites between patients treated with a placebo or 15
      +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or
      secondary-progressive MS. METHODS: Sixteen patients, recruited from a
      pharmacological study of DSG, and 11 healthy control subjects were investigated
      by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected
      volume initially contained a contrast-enhancing plaque, which was followed up for
      a period of 2 years. RESULTS: In contrast-enhancing plaques, Cho was
      significantly elevated and showed a significant reduction after both 3 and 12
      months. The initially normal Cr significantly increased between 3 and 12 months,
      and was negatively correlated with plaque volume on T1-weighted MR images. NAA
      initially showed normal values, a significant decrease at 1 month, and a slow
      recovery over 2 years. Myo-inositol did not show a clear tendency. The placebo
      group did not differ from the treated group, nor did the relapsing-remitting
      group differ from the secondary-progressive group. CONCLUSION: The contradictory
      time courses of Cr and NAA show that an absolute quantification in proton MR
      spectroscopy in MS is necessary to avoid a false interpretation of reduced NAA/Cr
      ratios. The increase in Cr is probably due to remyelination. The initial dip and
      later recovery of NAA seem to be related to diminishing edema and remyelination.

PMID- 10954273
TI  - Functional MR imaging activation after finger tapping has a shorter duration in
      the basal ganglia than in the sensorimotor cortex.
AB  - BACKGROUND AND PURPOSE: Repetitive motor tasks that produce sustained neuronal
      activity in the sensorimotor cortex produce transient neuronal activity in
      subcortical regions. We tested the hypothesis that a reference function modeling
      a transient hemodynamic response would more reliably detect activation in the
      basal ganglia than would a conventional reference function, which models a
      sustained hemodynamic response. METHODS: Functional MR imaging data were acquired
      in eight subjects performing an alternating-hand finger-tapping task.
      Postprocessing was performed by cross-correlation to two types of reference
      functions: one that models a sustained hemodynamic response to finger tapping and
      one that models an initial transient hemodynamic response. Activation in the
      sensorimotor cortex, supplementary motor area, cerebellum, thalamus, and corpus
      striatum was tabulated for each reference function. RESULTS: With the
      conventional boxcar reference function, activation was detected in the
      sensorimotor cortex, supplementary motor area, and cerebellum, but intermittently
      in the corpus striatum in all subjects. With the reference function for a
      transient response, activation in the corpus striatum was not detected in all
      subjects. CONCLUSION: In the corpus striatum, activation is detected more
      frequently with a reference function that models a transient response. Activated
      cortical and subcortical regions can be mapped with an alternating-hand finger
      tapping paradigm and a combination of reference functions.

PMID- 10954274
TI  - Magnetization transfer measurements of the hippocampus in patients with
      Alzheimer's disease, vascular dementia, and other types of dementia.
AB  - BACKGROUND AND PURPOSE: Although atrophy of structures in the medial temporal
      lobe has been considered an indication of Alzheimer's disease (AD), atrophic
      changes on MR images have also been associated with other dementing diseases and
      are not specific to AD. This study was undertaken to determine whether
      characteristic alterations in the hippocampus of patients with AD are detectable
      with magnetization transfer (MT) imaging. METHODS: Coronal MT imaging was
      performed in 35 patients with probable AD, in 14 patients with vascular dementia,
      in 13 patients with other types of dementia, and in 23 control subjects to
      measure MT ratios of the hippocampus. Medial temporal lobe atrophy was graded
      subjectively on a five-point scale. RESULTS: Scores of medial temporal lobe
      atrophy in all dementia groups were significantly higher than those in control
      subjects, but no differences were found among the dementia groups. MT ratios in
      the hippocampus were significantly lower in patients with AD than in those with
      non-AD dementia and in the control subjects; however, no differences were found
      between the non-AD dementia patients and the control subjects. MT ratio
      measurements were better than visual analysis of atrophy for differentiating AD
      patients from those with non-AD dementia (an overall discrimination rate of 77%
      versus 65%). MT ratios significantly correlated with scores on the Mini-Mental
      State Examination and with medial temporal lobe atrophy in AD patients but not in
      patients with non-AD dementia. CONCLUSION: MT measurements may be more specific
      than visual analysis in detecting structural damage of the hippocampus in AD
      patients and might be useful in discriminating AD from vascular dementia and
      other types of dementia.

PMID- 10954275
TI  - Demonstration of the medullary lamellae of the human red nucleus with high
      resolution gradient-echo MR imaging.
AB  - BACKGROUND AND PURPOSE: The human red nucleus is not a uniform structure. It is
      composed of caudally located magnocellular and rostrally located parvicellular
      subnuclei. In fact, the latter forms the bulk of the human red nucleus and can be
      subdivided histologically by two medullary lamellae into three parts. Because
      iron is deposited in the human red nucleus and gradient-echo sequences are more
      sensitive than spin-echo sequences in the detection of iron, a high-resolution
      gradient-echo MR sequence was used in this study to determine whether the
      medullary lamellae of the normal human red nucleus could be detected in vivo.
      METHODS: Ten healthy volunteers (seven men and three women, 27-48 years old) were
      examined with a high-resolution T2-weighted gradient-echo MR sequence using a 1.9
      T MR imager. The scanning parameters were 60/40/15 (TR/TE/excitations) with a
      flip angle of 20 degrees , a pixel size of 1 x 1 mm, and a slice thickness of 5
      mm. RESULTS: The medullary lamellae were depicted in all subjects in three
      imaging planes: coronal, oblique axial, and oblique sagittal. The signal
      intensity of the lamellae was consistently higher than that of other parts of the
      red nucleus on all images. With the lamellae, the parvicellular subnucleus of the
      human red nucleus can be divided into its subdivisions. CONCLUSION: High
      resolution gradient-echo MR imaging is capable of depicting the medullary
      lamellae of the normal human red nucleus in vivo.

PMID- 10954276
TI  - CNS involvement of virus-associated hemophagocytic syndrome: MR imaging
      appearance.
AB  - The MR imaging appearance of a case of virus-associated hemophagocytic syndrome
      complicated by diffuse CNS infiltration is presented. Virus-associated
      hemophagocytic syndrome is a rare condition, precipitated by viral infection and
      characterized by proliferation of benign histiocytes with phagocytosis. In severe
      cases, the CNS may be involved.

PMID- 10954277
TI  - Reversible tacrolimus-induced neurotoxicity isolated to the brain stem.
AB  - Diplopia, nystagmus, visual hallucinations, and internuclear ophthalmoplegia
      developed in a 30-year-old woman 84 days after she received a matched, unrelated
      bone marrow transplant for chronic myeloid leukemia. A regimen of tacrolimus had
      been administered since the transplantation was performed. MR imaging revealed
      bilaterally symmetric regions of signal abnormality with abnormal contrast
      enhancement in the brain stem. No supratentorial abnormality was present.
      Tacrolimus therapy was discontinued, and the symptoms resolved. MR imaging that
      was performed 10 days after tacrolimus was discontinued showed resolution of the
      abnormalities.

PMID- 10954278
TI  - Can induction of systemic hypotension help prevent nidus rupture complicating
      arteriovenous malformation embolization?: analysis of underlying mechanism
      achieved using a theoretical model.
AB  - BACKGROUND AND PURPOSE: Nidus rupture is a serious complication of intracranial
      arteriovenous malformation (AVM) embolotherapy, but its pathogenetic mechanisms
      are not well described. An AVM model based on electrical network analysis was
      used to investigate theoretically the potential role of hemodynamic perturbations
      for elevating the risk of nidus vessel rupture (Rrupt) after simulated AVM
      embolotherapy, and to assess the potential benefit of systemic hypotension for
      preventing rupture. METHODS: Five separate hypothetical mechanisms for nidus
      hemorrhage were studied: 1) intranidal rerouting of blood pressure; 2) extranidal
      rerouting of blood pressure; 3) occlusion of draining veins with glue; 4) delayed
      thrombosis of draining veins; and 5) excessively high injection pressures
      proximal to the nidus. Simulated occlusion of vessels or elevated injection
      pressures were implemented into the AVM model, and electrical circuit analysis
      revealed the consequent changes in intranidal flow, pressure, and Rrupt for the
      nidus vessels. An expression for Rrupt was derived based on the functional
      distribution of the critical radii of component vessels. If AVM rupture was
      observed (Rrupt > or = 100%) at systemic normotension (mean pressure [P] = 74 mm
      Hg), the theoretical embolization was repeated under systemic hypotension (minor
      P = 70 mm Hg, moderate P = 50 mm Hg, or profound P = 25 mm Hg) to assess the
      potential benefit of this maneuver in reducing hemorrhage rates. RESULTS: All
      five pathogenetic mechanisms under investigation were able to produce rupture of
      AVMs during or after embolotherapy. These different mechanisms had in common the
      capability of generating surges in intranidal hemodynamic parameters resulting in
      nidus vessel rupture. The theoretical induction of systemic hypotension during
      and after treatment was shown to be of significant benefit in attenuating these
      surges and reducing Rrupt to safer levels below 100%. CONCLUSION: The induction
      of systemic hypotension during and after AVM embolization would appear
      theoretically to be of potential use in preventing iatrogenic nidus hemorrhage.
      The described AVM model should serve as a useful research tool for further
      theoretical investigations of AVM embolotherapy and its hemodynamic sequelae.

PMID- 10954279
TI  - Histopathologic characteristics of a chronic arteriovenous malformation in a
      swine model: preliminary study.
AB  - BACKGROUND AND PURPOSE: The experimental induction of histologic transformations
      in microvessels of similar caliber to those of nidus vessels of cerebral
      arteriovenous malformations (AVMs) has not been attempted previously. Our goal
      was to examine preliminarily the histopathologic characteristics of nidus vessels
      and the angiographic features of a chronic AVM model in swine. METHODS: AVM
      models were fashioned from bilateral carotid retia mirabilia of seven swine after
      the surgical formation of large unilateral carotid-jugular fistulas. One AVM
      model was made for immediate use, whereas in the other six, follow-up angiography
      was obtained at varying intervals (2 to 180 days) after model creation. Light and
      electron microscopy, immunohistochemistry (using monoclonal antibodies against
      smooth muscle actin and PC10 against proliferating cell nuclear antigen), and
      histometry were performed on the nidus vessels of three swine: one acutely
      created, one 2 months old, and one 6 months old. RESULTS: Vascular dilatation and
      tortuosity of the main arterial feeder and draining vein were evident
      angiographically as early as 4 days after AVM creation, and were maximal in the 6
      month-old model. Compared with the acutely created nidus vessels, those in the
      two chronic models revealed disrupted and attenuated elastica and intimal
      hyperplasia that was focal ("cushions") or generalized, leading to luminal
      occlusion. Variable numbers of cells in the tunica media of chronic nidus vessels
      contained smooth muscle actin. PC10/proliferating cell nuclear antigen
      immunoreactivity was observed in the endothelium and subendothelial layers.
      Histometry showed increases in intimal hyperplasia and medial thickness in the
      chronic vessels. CONCLUSION: Nidus vessels in this chronic swine AVM model
      exhibited striking histologic changes similar to those seen in cerebral AVMs. The
      induced vessel growth seen angiographically and histologically in components of
      the chronic AVMs was consistent with the presence of persistently raised
      intravascular hemodynamic loads. This preliminary feasibility study suggests that
      the realistic histologic characteristics of this chronic AVM model are an
      attractive feature, and if confirmed in future, more comprehensive, studies would
      be of benefit in accurate histopathologic interpretation of the effects of
      superimposed experimental embolotherapy or radiosurgery. This model may provide a
      useful experimental tool to study the dynamic cellular and tissue events that
      dictate the development and natural history of AVMs.

PMID- 10954280
TI  - Change of spontaneous reaction of glue and lipiodol mixture during embolization
      after the addition of tungsten powder: in vitro study.
AB  - BACKGROUND AND PURPOSE: We have noted that glue-Lipiodol mixtures harden
      prematurely in the catheter during embolization of brain arteriovenous
      malformations. However, we observed that hardening of this embolic material does
      not occur when tungsten powder is added to the glue mixture. In order to clarify
      the effect of tungsten powder on the glue mixture, we evaluated the reaction time
      and hardness of the glue mixture in vitro after the addition of tungsten powder.
      We also measured the pH of the tungsten solution. METHODS: Six lots of Lipiodol
      and three lots of Histoacryl Blue were mixed in a 5-cc bottle with a 50% to 25%
      glue concentration (glue:Lipiodol = 1:1 to 1:3) and this mixture was observed for
      2 weeks. The hardness of the polymerized glue mixture was categorized as liquid,
      gel, semi-solid, or solid. Various series of experiments were performed after the
      addition of tungsten powder (0.2 g) and blood (a drop) into the glue mixture. We
      also separately mixed tungsten and tantalum powder in tubes, each with 5 mL of
      distilled water, and then measured the pH of these three times. The mixed amounts
      of tungsten and tantalum ranged from 0.1 to 0.5 mg. RESULTS: In a 50% glue
      concentration, the glue mixture turned into a solid cast within 48 hours. In a
      25% concentration, the glue mixture turned into gel within 24 hours. The casts
      became solid in the 50% and gelled in the 25% concentration, and solid or gel in
      28% and 33% glue mixture concentrations. The addition of tungsten powder to 50%
      and 25% glue mixture concentrations caused the glue mixtures to remain in a
      liquid state for 2 weeks regardless of the Lipiodol products used. Measurement of
      acidity achieved using a pH meter in 5 cc of distilled water with tungsten powder
      (0.1 to 0.5 g) revealed a change of pH from 3.5 to 2.6 according to the amount of
      tungsten added. Tantalum revealed weak acidity, with a pH range from 6.4 to 5.7.
      The addition of blood immediately caused the mixture to become solid in 50% and
      semi-solid in 25% glue concentrations. CONCLUSION: The reaction time of the glue
      mixture differed according to the lot number of the Lipiodol. The addition of
      tungsten powder appeared to prevent premature cast formation by decreasing the pH
      with a mechanism similar to that of adding acetic acid.

PMID- 10954281
TI  - Endovascular management of extracranial carotid artery dissection achieved using
      stent angioplasty.
AB  - BACKGROUND AND PURPOSE: Dissection of the carotid artery can, in certain cases,
      lead to significant stenosis, occlusion, or pseudoaneurysm formation, with
      subsequent hemodynamic and embolic infarcts, despite anticoagulant therapy. We
      sought to determine the therapeutic value of stent-supported angioplasty
      retrospectively in this subset of patients who are poor candidates for medical
      therapy. METHODS: Five men and five women (age range, 37-83 years; mean age, 51.2
      years) with dissection of the internal (n=9) and common (n=1) carotid artery were
      successfully treated with percutaneous endovascular balloon angioplasty and stent
      placement. The etiology was spontaneous in five, iatrogenic in three, and
      traumatic in two. Seven of the treated lesions were left-sided and three were
      right-sided. RESULTS: The treatment significantly improved dissection-related
      stenosis from 74+/-5.5% to 5.5+/-2.8%. Two occlusive dissections were
      successfully recanalized using microcatheter techniques during the acute phase.
      Multiple overlapping stents were needed in four patients to eliminate the inflow
      zone and false lumen and establish an angiographically smooth outline within the
      true lumen. There was one case of retroperitoneal hemorrhage, but there were no
      procedural transient ischemic attacks (TIAs), minor or major strokes, or deaths
      (0%). Clinical outcome at latest follow-up (16.5+/-1.9 months) showed significant
      improvements compared with pretreatment modified Rankin score (0.7+/-0.3 vs 1.8+/
      0.44) and Barthel index (99.5+/-0.5 vs 80.5+/-8.9). One delayed stroke occurred
      in a treated patient with contralateral carotid occlusion following a hypotensive
      uterine hemorrhage at 8 months; the remaining nine patients have remained free of
      TIA or stroke. CONCLUSION: In select cases of carotid dissection associated with
      critical hemodynamic insufficiency or thromboembolic events that occur despite
      medical therapy, endovascular stent placement appears to be a safe and effective
      method of restoring vessel lumen integrity, with good clinical outcome.

PMID- 10954282
TI  - Intracranial vertebrobasilar stenosis: angioplasty and follow-up.
AB  - BACKGROUND AND PURPOSE: When medication fails to improve symptoms of
      atherosclerotic stenosis of the intracranial vertebral and basilar arteries,
      percutaneous transluminal angioplasty (PTA) is considered. However, because
      investigators disagree on the usefulness of this procedure, we conducted a
      retrospective study to evaluate the indications, efficacy, and safety of PTA.
      METHODS: Twenty patients underwent PTA of the vertebral (n = 14) or basilar (n =
      6) artery, 18 for neurologic signs and symptoms of arterial stenosis that
      recurred or progressed despite pharmacotherapy and two prophylactically.
      Neurologic examinations were performed before and after the procedure and
      arterial patency was evaluated at follow-up by digital subtraction angiography
      and/or MR angiography. Imaging follow-up was available for 14 (70%) of the 20
      patients, neurologic follow-up for 15 (75%). RESULTS: The stenosis was
      successfully dilated in all patients, and on follow-up neuroradiologic
      examinations, vessel patency could be seen in 12 (86%) of 14 patients. Only one
      (7%) of 15 patients who returned for a follow-up neurologic examination had new
      symptoms (caused by occlusion of the vertebral artery 4 months after the
      procedure). One patient had a reversible neurologic deficit and one had
      hemiparesis after PTA. No patient died as a result of PTA. CONCLUSION: In our
      study, PTA of intracranial vertebrobasilar arteries was associated with a low
      mortality and morbidity rate and with a high degree of patency. This technique
      may therefore be regarded as an effective means of improving the patency of
      stenotic arteries. In selective cases, it might be considered for use
      prophylactically.

PMID- 10954283
TI  - Wada testing in pediatric patients by use of propofol anesthesia.
AB  - BACKGROUND AND PURPOSE: Wada testing may provide important information for
      surgical planning in pediatric patients with medically refractory epilepsy, but
      it is often not used because of the difficulties in performing the angiographic
      portion of the procedure in conscious children. We reviewed our experience using
      propofol, a short-acting IV administered anesthetic agent, for pediatric patients
      undergoing Wada testing. METHODS: In a retrospective review of Wada tests
      performed on patients younger than 18 years, we identified 24 cases in which
      propofol anesthesia was used. We reviewed the medical records of these patients,
      with particular reference to dose of propofol, physiological parameters during
      anesthesia, and adequacy of neuropsychological testing after emergence from
      anesthesia. RESULTS: Patients ranged in age from 6 to 16 years (mean age, 12.5
      years). Propofol induced mild reductions in blood pressure (12.4% for systolic
      and 13.9% for diastolic blood pressure) and heart rate (mean reduction of 4.7%),
      which did not require specific treatment in any patient. Recovery from anesthesia
      was smooth and rapid, allowing initiation of Wada testing within 15 to 25 minutes
      of cessation of propofol. Wada testing was successfully accomplished in all
      patients. CONCLUSION: Propofol provided rapid induction of anesthesia, was
      administered without endotracheal intubation, and did not cause substantial
      changes in cardiorespiratory parameters. Propofol anesthesia allowed controlled
      angiography among patients as young as 6 years and did not interfere with
      neuropsychological testing.

PMID- 10954284
TI  - Endovascular treatment of cerebral artery aneurysms during pregnancy: report of
      three cases.
AB  - Historically, surgical management of cerebral aneurysms during pregnancy has been
      controversial. Debate originally focused on early versus late intervention,
      before or after delivery of the fetus. More recently, treatment has centered on
      rapid intervention. We describe the endovascular treatment of cerebral artery
      aneurysms with Guglielmi detachable coils in three pregnant women.

PMID- 10954285
TI  - Use of three-dimensional Guglielmi detachable coils in the treatment of wide
      necked cerebral aneurysms.
AB  - A three-dimensional Guglielmi detachable coil (3D-GDC) has been developed that is
      designed specifically to bridge the neck of an aneurysm with coil loops, thereby
      facilitating retention of additional coils placed within the aneurysm. Nine wide
      necked cerebral aneurysms were successfully embolized using the 3D-GDC, provided
      that the dome-to-neck ratio was 1.5 or greater.

PMID- 10954286
TI  - The pterygopalatine fossa: postoperative MR imaging appearance.
AB  - BACKGROUND AND PURPOSE: The pterygopalatine fossa (PPF) is an important anatomic
      location of the deep portion of the face. It is essential to review this area on
      both pre- and posttreatment studies of head and neck malignancies to assess local
      extent of disease or recurrence and perineural tumor spread. The purpose of this
      study was to review the postoperative appearance of the PPF on MR images.
      METHODS: Imaging and clinical data of 10 patients who underwent surgical
      resection of tumor in which the PPF was violated at surgery were reviewed.
      Patients were included in the study if there was no imaging or clinical evidence
      of tumor in the PPF pre- or postoperatively. Postoperative MR studies were
      examined to assess the appearance of the PPF. RESULTS: The PPF is consistently
      and persistently abnormal after surgical violation. There is loss of the normal
      T1 signal hyperintensity and abnormal, increased contrast enhancement, as seen on
      fat-suppressed T1-weighted images. These postoperative changes are strikingly
      similar to those of tumor involvement. CONCLUSION: After surgical violation, the
      PPF will always appear abnormal on MR images, and the expected imaging findings
      must be recognized to avoid the misdiagnosis of tumor recurrence.

PMID- 10954287
TI  - Dynamic helical CT of T1 and T2 glottic carcinomas: predictive value for local
      control with radiation therapy.
AB  - BACKGROUND AND PURPOSE: Tumor volume and cartilage invasion have been suggested
      as prognostic factors of glottic carcinomas following definitive radiation
      therapy. Radiologic examinations provide additional information regarding the
      deep extension of tumor. We determined whether dynamic helical CT can predict
      local control of early (T1 and T2 stage) glottic carcinomas treated with
      definitive radiation therapy. METHODS: Sixty-eight patients with early glottic
      carcinoma evaluated on pretreatment dynamic helical CT were treated with
      definitive radiation therapy. Tumor detectability, maximum dimension, tumor
      volume, and involvement of anatomic subsites (anterior commissure, ventricle,
      subglottic region, and thyroid and arytenoid cartilages) were determined by
      consensus by three radiologists without previous knowledge of the clinical
      information. The CT findings were correlated with local control. RESULTS: The two
      year local control rate was 76%; 91% for T1 and 60% for T2 lesions. Univariate
      analysis revealed clinical T stage, tumor detectability, maximum dimension, tumor
      volume, anterior commissure involvement, ventricle involvement, and thyroid
      cartilage involvement as significant prognostic factors. Thyroid cartilage
      involvement was an independent predictor by multivariate analysis. The lesions
      separate from the thyroid cartilage had a 95% probability of local control,
      whereas the lesions adjacent to the cartilage had only a 42% control rate.
      CONCLUSION: Dynamic helical CT provides prognostic information for the results of
      definitive radiation therapy. Patients with a tumor adjacent to the thyroid
      cartilage had an increased risk of local failure.

PMID- 10954288
TI  - Incidence and clinical significance of frontal sinus or orbital entry during
      pterional (frontotemporal) craniotomy.
AB  - BACKGROUND AND PURPOSE: Frontal sinus entry, orbital entry, or both may occur
      during pterional craniotomy for microsurgical clipping of aneurysms. We sought to
      determine the incidence and clinical significance of these findings on
      postoperative CT scans. METHODS: Eighty-two postoperative CT scans of the head
      obtained from 81 patients (64 women, 17 men; age range, 25-80 years) were
      retrospectively reviewed over a 1-year period. These scans were reviewed
      independently by two blinded neuroradiologists for the presence and degree of
      orbit and frontal sinus entry that may have occurred during craniotomy. Clinical
      charts, operative notes, and discussions with the patients' neurosurgeons were
      reviewed to determine the clinical management and significance of these findings.
      RESULTS: Of the total 82 craniotomies reviewed, 77 (94%) had been performed via
      the pterional approach (43 right, 34 left). Twenty-three (30%) of these 77
      studies revealed some evidence of penetration into the orbit or frontal sinus
      (orbit=65.2% [15/23]; frontal sinus=30.4% [7/23]; both=4.4% [1/23]). Only five of
      16 patients with radiographic orbital penetration had evidence of involvement of
      intraorbital contents (ie, thickened lateral rectus, fat herniation, intraorbital
      air). Chart review revealed no complication or change in management. Of the seven
      patients with frontal sinus entry, three had mucosal exenteration and packing
      with antibiotic-coated gelfoam. No delayed complications (ie, persistent fever,
      mucocele, cerebrospinal fluid leak, air leak, or meningitis) were identified
      (follow-up period, 18-29 months). CONCLUSION: Frontal sinus or orbital entry is
      not uncommon after pterional craniotomy, but the incidence of immediate
      complications is rare.

PMID- 10954289
TI  - Jacobson's nerve schwannoma presenting as middle ear mass.
AB  - Schwannoma is one of the common benign middle ear space tumors. Middle ear space
      schwannomas may originate from the nerves of the tympanic cavity or by extensions
      from outside the middle ear space. In the English-language literature, the facial
      nerve and chorda tympani nerve, but not yet the tympanic branch of
      glossopharyngeal nerve (Jacobson's nerve), have been reported as the origins of
      intrinsic middle ear space schwannomas. We present the clinical and radiologic
      features of a middle-space schwannoma originating from Jacobson's nerve, and
      suggest that such a tumor be included in the differential diagnosis of middle ear
      tumors.

PMID- 10954290
TI  - Unilateral semicircular canal aplasia in Goldenhar's syndrome.
AB  - A patient with Goldenhar's syndrome (oculoauriculovertebral dysplasia) and
      unilateral aplasia of all semicircular canals is presented. This is the first
      report of such a finding and may support the hypothesis that Goldenhar's syndrome
      and the CHARGE association have a common pathogenetic mechanism.

PMID- 10954291
TI  - Castleman's disease in the retropharyngeal space: CT and MR imaging findings.
AB  - We report CT and MR imaging findings in a case of Castleman's disease involving
      the retropharyngeal space in a middle-aged woman. On CT scans, a well-marginated,
      homogeneous, and densely enhancing mass was detected in the right retropharyngeal
      space. The mass was isointense to the muscle on T1-weighted MR images,
      hyperintense to the muscle on T2-weighted MR images, and showed homogeneous,
      strong enhancement on contrast-enhanced T1-weighted MR images. The linear
      hypointense signal in an arborizing pattern was observed within the mass on all
      pulse sequences.

PMID- 10954292
TI  - Intrathyroidal lymphoepithelial (branchial) cyst: sonographic features of a rare
      lesion.
AB  - Intrathyroidal lymphoepithelial cysts are rare, and only 15 such cases have been
      reported. Although sonography has been performed in some cases, the findings have
      not been discussed previously. Despite its rarity, the sonographic appearances of
      this lesion are similar to those of other commonly encountered congenital cystic
      lesions in the head and neck, such as thyroglossal duct cysts and second
      branchial cleft cysts, and this may provide a clue to its diagnosis. We describe
      the sonographic appearances of intrathyroidal lymphoepithelial cysts.

PMID- 10954293
TI  - MR line-scan diffusion imaging of the spinal cord in children.
AB  - Diffusion imaging has been widely used in the brain, but its application in the
      spinal cord has been limited. Using line-scan diffusion imaging (LSDI), a
      technique that is less sensitive to magnetic susceptibility and motion artifacts
      than are other diffusion techniques, we have successfully imaged the spinal cord
      in children. The apparent diffusion coefficient and relative diffusion anisotropy
      of the normal spinal cord were measured. LSDI was compared with echo-planar
      diffusion imaging of the spine in three patients.

PMID- 10954294
TI  - Intracranial and intraspinal meningeal melanocytosis.
AB  - We describe a 35-year-old man with a history of remote closed head injury who
      presented with new neurologic deficits. A noncontrast head CT scan showed
      hyperattenuation involving both temporal lobes, frontal lobes, basal meninges,
      and cerebellum. A subsequent contrast-enhanced MR examination of the brain showed
      enhancement in the basal cisterns extending into the upper cervical spine and
      throughout the spinal canal. Gross, histologic, and immunohistochemical analysis
      revealed meningeal melanocytoma.

PMID- 10954296
TI  - In re: Serbinenko FA. Balloon catheterization and occlusion of major cerebral
      vessels. J Neurosurg 1974;41:1974.

PMID- 10954295
TI  - Localized proton MR spectroscopy of the allocortex and isocortex in healthy
      children.
AB  - BACKGROUND AND PURPOSE: The human allocortex is different from the isocortex in
      neuroglial cytoarchitecture. The purpose of this study was to compare metabolic
      data of the allocortex with those of the isocortex by using localized proton MR
      spectroscopy. METHODS: Short-TE stimulated-echo acquisition mode proton MR
      spectroscopy (TR/TE = 3000/30) was applied to the allocortex of the temporal lobe
      and isocortex of the parietal or frontal lobe in 30 healthy children (19 boys and
      11 girls, 3-14 years old). Peak intensities of N-acetylaspartate (NAA), choline
      containing compounds (Cho), and myo-inositol (mI) relative to creatine and
      phosphocreatine (Cr) were calculated. Metabolic data from the investigated
      regions were compared. RESULTS: NAA/Cr was significantly lower in the allocortex
      than in the isocortex of the parietal or frontal lobe: 1.05 +/- 0.12 (n = 33) vs.
      1.36 +/- 0.10 (n = 28) or 1.32 +/- 0.10 (n = 12), respectively. Cho/Cr and mI/Cr
      were significantly higher in the allocortex than in the isocortex: 0.84 +/- 0.11
      vs. 0.56 +/- 0.06 or 0.75 +/- 0.10; 0.78 +/- 0.15 vs. 0.54 +/- 0.08 or 0.66 +/-
      0.09, respectively. In the isocortex, NAA/Cr was not different but Cho/Cr and
      mI/Cr were significantly higher in the frontal cortex than in the parietal
      cortex. CONCLUSION: Clear metabolic differences were observed between the
      allocortex and isocortex.

PMID- 10954297
TI  - Low back pain, lead aprons, and the angiographer.

PMID- 10954298
TI  - Contrast-enhanced spiral CT of the head and neck.

PMID- 10954299
TI  - Hypertensive brain stem encephalopathy.

PMID- 10954300
TI  - Calcium stone fragility is predicted by helical CT attenuation values.
AB  - BACKGROUND AND PURPOSE: Helical CT has become the preferred method for imaging
      urinary calculi, and so it would be useful if data from helical CT could also be
      used to predict the number of shockwaves (SWs) needed to break a given stone.
      METHODS AND MATERIALS: We measured the number of SWs required to comminute
      calcium stones in vitro. RESULTS: The SW requirement correlated with stone size
      (volume, weight, diameter) and with helical CT attenuation values when the scans
      were performed at 3-mm collimation. When CT scans were performed at 1-mm
      collimation, the number of SWs needed for comminution did not correlate with
      helical CT attenuation values. This result indicates that the correlation with 3
      mm scans was attributable to volume-averaging effects, in which smaller stones
      yield smaller attenuation values. That is, attenuation values from helical CT at
      larger beam collimation widths contain information about stone size that can be
      exploited to predict the fragility of calcium stones. We observed that for
      calcium stones, the number of SWs to comminution was generally less than half the
      stone CT attenuation value in Hounsfield units. This "half-attenuation rule"
      predicted the number of SWs needed to complete fragmentation for 95% of calcium
      stones (24/24 calcium oxalate monohydrate, 13/13 hydroxyapatite, 8/10 brushite
      stones). CONCLUSION: This in vitro study suggests that it may be possible to
      predict effective SW dose using helical CT prior to lithotripsy.

PMID- 10954301
TI  - Is there a simpler method for predicting lower pole stone clearance after
      shockwave lithotripsy than measuring infundibulopelvic angle?
AB  - BACKGROUND AND PURPOSE: Several anatomic factors influence the clearance of lower
      pole stones treated with shockwave lithotripsy (SWL). One of these is the
      infundibulopelvic angle, but its measurement is complex. METHODS: We proposed a
      more simple measure of caliceal dependence, the caliceal pelvic height (CPH),
      which we defined as the distance between a horizontal line from the lowermost
      point of the calix containing the stone to the highest point of the lower lip of
      the renal pelvis. RESULTS: In 62 patients who had SWL for solitary lower pole
      stones, a CPH < 15 mm was associated with a stone clearance rate of 92%, whereas
      with a CPH > or = 15 mm, the clearance rate was only 52% (p < 0.05). A majority
      (74%) of the patients with an infundibular width of > or = 5 mm were rendered
      stone free compared with 40% of those with a width of < 5 mm (p < 0.05).
      CONCLUSION: Measurement of the CPH, in conjunction with other anatomic factors,
      may more accurately predict the outcome of SWL in patients with lower pole
      stones.

PMID- 10954302
TI  - To stent or not to stent? That is still the question.
AB  - BACKGROUND AND PURPOSE: Most patients are stented after ureteroscopy for stone
      extraction. This practice necessitates a second procedure to remove the stent,
      with its inherent morbidity. The aim of our study was to determine whether
      routine stenting of the ureter is really necessary after ureteroscopy. PATIENTS
      AND METHODS: This prospective study evaluated 26 men and 18 women admitted for
      elective distal ureteral stone fragmentation. The stones ranged in size from 6 mm
      to 1 cm. Of the series, 16 patients (10 men) had been stented prior to
      ureteroscopy. A 9F semirigid ureteroscope was used in 31 cases, and a 7.5F
      semirigid ureteroscope was used in the other 11 cases; there was no need for
      ureteral orifice dilatation with either ureteroscope. Ballistic intracorporeal
      lithotripsy was performed in all cases with the Swiss Lithoclast; all stone
      fragments were retrieved with a 3F helical basket. The patients were followed up
      as inpatients for 24 hours and reviewed in the clinic 1 week later with a request
      to report if they felt significant discomfort or loin pain or became feverish.
      RESULTS: Only one patient (male) had to be readmitted with loin pain. Two others
      (both women) complained when they attended for follow-up of having had dull lower
      abdominal pain and some frequency. CONCLUSIONS: The low incidence of
      complications in this preliminary study suggests that routine stenting is not
      necessary after ureteroscopy. The chief exception to this statement is patients
      who had a difficult and prolonged stone fragmentation.

PMID- 10954303
TI  - Pentosanpolysulfate coating of silicone reduces encrustation.
AB  - BACKGROUND AND PURPOSE: A significant problem associated with catheterization in
      the urinary tract is the encrustation of the catheter materials. One approach to
      reducing encrustation is to alter the surface properties of the catheters. We
      evaluated the effectiveness of coating with pentosanpolysulfate (PPS), a
      semisynthetic polysaccharide similar to heparin, in reducing encrustation and the
      foreign-body inflammatory response to silicone stents in the bladders of male New
      Zealand White rabbits. MATERIALS AND METHODS: Sixteen rabbits were divided into
      three groups to receive placement in their bladders of uncoated (N = 7), PPS
      coated (N = 7), or sham matrix-processed silicone rings (N = 2) via open
      cystotomy. After 50 days of maintenance on normal food and water, all rabbits
      were sacrificed, and the air-dried, unfixed silicone ring surfaces were examined
      by scanning electron microscopy. Bladders and remaining silicone rings were
      removed and preserved separately. Silicone rings, cleaned of all encrustation,
      were stained with toluidene blue to determine the presence or absence of PPS
      coating on the surface. RESULTS: Histologic examination revealed normal tissue in
      bladder sections exposed to coated silicone rings and an inflammatory response in
      sections from bladders having uncoated silicone rings. Coating with PPS was
      associated with an eightfold reduction in the amount of encrustation of silicone
      and a marked reduction in the inflammatory response of the bladder wall to the
      foreign body. CONCLUSIONS: A PPS coating may be useful in reducing the
      encrustation of long-term indwelling silicone stents or catheters in the human
      urinary tract.

PMID- 10954304
TI  - Ureteroscopic management of recurrent renal cystine calculi.
AB  - BACKGROUND AND PURPOSE: Patients with recurrent cystine nephrolithiasis
      oftentimes require multiple procedures for stone removal. As the majority of
      cystine stones are resistant to the effects of shockwave lithotripsy, repeat
      percutaneous surgery is often required and may cause renal damage. Moreover,
      repeat percutaneous access may become more difficult as perinephric fibrosis
      develops. Small-caliber ureteroscopes along with the holmium laser now enable
      routine intrarenal ureteroscopic access to symptomatic renal stones. Herein, we
      present our experience in managing recurrent renal cystine calculi using flexible
      ureterorenoscopy and assess whether such an approach may be used as an
      alternative to percutaneous surgery in selected patients. PATIENTS AND METHODS:
      Three patients with large-volume (mean diameter 22 mm) renal cystine stones were
      managed with a 7.5F flexible ureterorenoscope combined with holmium laser
      lithotripsy to fragment the stones completely. RESULTS: The mean treatment time
      was 97 minutes, with successful fragmentation in all cases. Two of the three
      patients were completely stone free on follow-up intravenous urography, with the
      third patient having only small-volume residual fragments in a lower pole calix.
      All patients are currently asymptomatic and are being maintained on high oral
      fluid intake, urinary alkalization with potassium citrate, and alpha
      mercaptopropionylglycine to reduce urinary cystine excretion. CONCLUSION:
      Flexible ureterorenoscopy with holmium laser lithotripsy provides a reasonable
      alternative for the management for recurrent cystine calculi in patients who are
      not candidates for repeat percutaneous procedures. Although it is time consuming,
      complete stone fragmentation, along with clearance of fragments, can be achieved
      in the majority of patients.

PMID- 10954305
TI  - Feasibility of telementoring between Baltimore (USA) and Rome (Italy): the first
      five cases.
AB  - BACKGROUND AND PURPOSE: Telemedicine is the use of telecommunication technology
      to deliver healthcare. Telementoring has been developed to allow a surgeon at a
      remote site to offer guidance and assistance to a less-experienced surgeon. We
      report on our experience during laparoscopic urologic procedures with mentoring
      between Rome, Italy, and Baltimore, USA. MATERIAL AND METHODS: Over a period of 3
      months, two laparoscopic left spermatic vein ligations, one retroperitoneal renal
      biopsy, one laparoscopic nephrectomy, and one percutaneous access to the kidney
      were telementored. Transperitoneal laparoscopic cases were performed with the use
      of AESOP, a robotic for remote manipulation of the endoscopic camera. A second
      robot, PAKY, was used to perform radiologically guided needle orientation and
      insertion for percutaneous renal access. In addition to controlling the robotic
      devices, the system provided real-time video display for either the laparoscope
      or an externally mounted camera located in the operating room, full duplex audio,
      telestration over live video, and access to electrocautery for tissue cutting or
      hemostasis. RESULTS: All procedures were accomplished with an uneventful
      postoperative course. One technical failure occurred because the robotic device
      was not properly positioned on the operating table. The round-trip delay of image
      transmission was less than 1 second. CONCLUSION: International telementoring is a
      feasible technique that can enhance surgeon education and decrease the likelihood
      of complications attributable to inexperience with new operative techniques.

PMID- 10954306
TI  - Partial laparoscopic adrenalectomy for aldosterone-producing adenoma: short-and
      long-term results.
AB  - BACKGROUND AND PURPOSE: Laparoscopic surgery for adrenal gland tumors is the gold
      standard operative approach now. Adrenal-sparing surgery has special indications.
      We demonstrated the safety and feasibility of performing adrenal-sparing surgery
      by means of laparoscopy for aldosterone-producing adenoma (Conn's syndrome).
      PATIENTS AND METHODS: Between 1995 and 1999, seven patients with Conn's syndrome
      had laparoscopic adrenal-sparing resection of their tumors. These patients were
      followed up by means of radiology and biochemistry. RESULTS: All seven patients
      had successful laparoscopic surgery without complications. Most patients were
      discharged in 2 to 6 days (mean 3 days). At follow-up, the six patients
      investigated had normal blood pressure. No recurrences have been encountered with
      a median follow-up of 12 months in these six patients. CONCLUSIONS: Adrenal
      sparing resection of tumors causing primary hyperaldosteronism is technically
      feasible by means of laparoscopy. This procedure has the advantage of keeping a
      greater reserve of normal adrenal tissue and of rapid postoperative recovery.

PMID- 10954307
TI  - Use of water jet resection in organ-sparing kidney surgery.
AB  - BACKGROUND AND PURPOSE: The morbidity of organ-sparing renal surgery is related
      to intraoperative hemorrhaging and secondarily to urinary fistulae and urinoma.
      Various tools have been developed for gentle transection and precise control of
      bleeding. Water jet technology is already established in clinical practice for
      surgery of the liver and other parenchymatous organs. We report our clinical
      experience with a new water jet resection device in kidney surgery and the
      histologic effects of water jet resection on kidney tissue. PATIENTS AND METHODS:
      A series of 24 patients underwent open surgery for renal-cell carcinoma,
      nephrolithiasis, complicated cysts, or oncocytoma. In tumor patients, a partial
      nephrectomy; in two stone patients, a nephrolithotomy; and in the third stone
      patient, a lower-pole resection were performed. The cysts and the oncocytoma were
      enucleated in toto. In one patient, an endoscopic pyeloplasty was performed
      because of ureteropelvic stenosis. Tissue samples were investigated
      histologically using standard light microscopy after hematoxylin-eosin staining
      and compared with those subjected to thermal dissection techniques. RESULTS: The
      water jet produced a corridor in the desired dissection line without interfering
      with the intrarenal vessels and pelvicalical system. This way, precise hemostasis
      was possible, and damages to the surrounding tissue was avoided. Resection took
      between 14 and 40 minutes with minimal intraoperative blood loss. No significant
      postoperative complications occurred. Histologic evaluation demonstrated a sharp
      dissection line without thermal alterations or deep necrosis. Only a small
      disruption zone could be seen at the margins of the dissection. CONCLUSIONS:
      Water jet resection is a gentle method for dissection of kidney tissue.
      Histologic examination confirmed minimal traumatic parenchymal alteration. In our
      opinion, the water jet dissector is a useful device for renal transection in
      organ-sparing kidney surgery.

PMID- 10954308
TI  - Metabolic and urinary risk factors associated with Randall's papillary plaques.
AB  - BACKGROUND AND PURPOSE: Increasing evidence suggests that Randall's plaques
      contribute to the pathogenesis of urinary stone formation. The purpose of our
      study was to evaluate the urinary risk factors of stone patients who underwent
      endoscopic mapping of their calices for Randall's plaques. PATIENTS AND
      MATERIALS: Patients (N = 143) having endoscopic procedures to remove upper tract
      calculi or for other purposes underwent mapping of their calices for Randall's
      plaques. Plaque incidence and pattern were correlated with the stone composition
      and urinary risk factors found on subsequent metabolic evaluation. RESULTS:
      Papillary plaques were found more commonly in patients having calcium oxalate
      stones than in patients with other stone types and patients without a history of
      stones. Papillary plaque incidence and pattern did not correlate with any
      specific urinary risk factor; however, patients with plaques tended to exhibit a
      higher incidence of all risk factors. Plaque severity tended to be greater in
      patients exhibiting hypercalciuria. CONCLUSIONS: Randall's plaques are found most
      frequently in patients with calcium oxalate stones and are most important in the
      pathogenesis of calcium oxalate nephrolithiasis. Stone patients with papillary
      plaques are more likely to exhibit abnormalities in their urinary milieu than are
      patients without papillary plaques.

PMID- 10954309
TI  - Use of permanent interstitial temperature self-regulating rods for ablation of
      prostate cancer.
AB  - BACKGROUND AND PURPOSE: We have examined a new technique for the thermal
      treatment of prostate cancer involving the percutaneous placement of small
      magnetic alloy rods into the gland in a procedure analogous to the placement of
      permanent brachytherapy seeds. When the patient and the implanted rods are placed
      in an extracorporeal alternating magnetic field, the rods heat and can produce
      tissue necrosis. The rods are temperature self-regulating and produce
      temperatures no higher than their preprogrammed regulation value. The rods are
      biocompatable permanent implants, comprised of cobalt and palladium. MATERIALS
      AND METHODS: We examined rods that heat to 55 degrees, 60 degrees, and 70 degrees
      C. Patients are treated for 1-hour sessions and easily have multiple sessions.
      RESULTS: Isolated rods produced little or asymmetrical necrosis. However, arrays
      of 70 degrees C rods placed within 1 cm of each other caused consistent necrosis
      between the rods. The temperature at the edge of the array dropped off quickly,
      and therefore, the rods can be placed within 2 mm of the capsule even posteriorly
      near the rectum. CONCLUSIONS: Arrays of high-temperature rods can be employed for
      tissue ablation, while lower-temperature arrays could be used to produce
      hyperthermia in order to achieve synergism with adjuvant radiation therapy. The
      technique is applicable in an outpatient setting.

PMID- 10954310
TI  - Transrectal high-intensity focused ultrasound: minimally invasive therapy of
      localized prostate cancer.
AB  - BACKGROUND AND PURPOSE: Criteria for determining the durability of the response
      to transrectal high-intensity focused ultrasound (HIFU) ablation of prostate
      cancer have been established by calculating progression-free probability.
      PATIENTS AND METHODS: A series of 82 patients (mean age 71 +/- 5.7 years) with
      biopsy-proven localized (stage T1-T2) cancer who were not suitable candidates for
      radical surgery underwent transfectal HIFU ablation with the Ablatherm machine.
      The mean follow-up was 17.6 months (range 3-68 months). The mean serum prostate
      specific antigen (PSA) value and mean prostate volume were 8.11 +/- 4.64 ng/mL
      and 34.9 +/- 17.4 cm3, respectively. Progression was rigidly defined as any
      positive biopsy result, regardless of PSA concentration, or three successive PSA
      increases for patients with a negative biopsy (PSA velocity > or = 0.75). Times
      to specific events (positive biopsy and PSA elevation) were analyzed with the
      Kaplan-Meier survival method. RESULTS: Overall, 62% of the patients exhibited no
      evidence of disease progression 60 months after transrectal HIFU ablation. In
      particular, the disease-free rate was 68% for the moderate-risk group of 50
      patients (PSA < 15.0 ng/mL, Gleason sum < 8, prostate volume < 40 cm3, and number
      of positive biopsies < 5). For the low-risk group of 32 patients (PSA < 10 ng/mL
      and Gleason sum < 7), the disease-free survival rate was 83%. CONCLUSION:
      Transrectal HIFU prostate ablation is an effective therapeutic alternative for
      patients with localized prostatic adenocarcinoma.

PMID- 10954311
TI  - Holmium laser enucleation of the prostate for glands larger than 100 g: an
      endourologic alternative to open prostatectomy.
AB  - BACKGROUND AND PURPOSE: Treatment of the large (>100 g) prostatic adenoma often
      involves open prostatectomy, with its attendant risks and morbidity. Enucleation
      of the entire adenoma endoscopically is possible with the holmium:YAG laser and
      tissue removal from within the bladder by a transurethral tissue morcellator.
      These patients can usually be discharged from the hospital the following day
      without a catheter. PATIENTS AND METHODS: A series of 43 patients with prostates
      100 g was followed for 6 months after laser resection. RESULTS: The mean
      morcellation time was 16.1 minutes. The mean catheter time was 19.7 hours, and
      the mean hospital time was 28.4 hours. One patient required readmission for
      evacuation of tissue fragments. The average AUA Symptom Score declined from 23.5
      preoperatively to 2.8 at 6 months postoperatively, and the mean Qmax increased
      from 9.0 mL/sec to 24.8 mL/sec. CONCLUSION: The holmium:YAG laser can be used to
      enucleate the adenoma in a large prostate in much the way the surgeon's finger
      does during open prostatectomy.

PMID- 10954312
TI  - Results of holmium laser resection of the prostate for benign prostatic
      hyperplasia.
AB  - PURPOSE: To assess the results of holmium laser resection of the prostate (HoLRP)
      in the treatment of benign prostatic hyperplasia. PATIENTS AND METHODS: Since
      October 1996, 259 patients have undergone elective HoLRP. Peak urinary flow rates
      (Qax), IPSS scores, and duration of catheterization and hospital stay from
      admission to discharge catheter free were used as outcome measures. RESULTS:
      There were no perioperative deaths nor cases of transurethral resection syndrome.
      Two patients required blood transfusion. The mean duration of catheterization was
      1.6 days and the mean hospital stay 2.9 days. The mean IPSS decreased from 21.0
      preoperatively to 7.0 at 1 year, whilst the Qmax increased from 10.5 mL/sec to
      20.5 mL/sec. CONCLUSION: The HoLRP technique is a safe and effective treatment
      for benign prostatic hyperplasia, allowing resection of the prostate at the level
      of the capsule with minimal bleeding or fluid absorption and with results
      equivalent to those of standard transurethral resection.

PMID- 10954313
TI  - Scapulohumeral arthrodesis for post-traumatic proximal humeral loss using
      vascularized fibular transplantation and allograft bone.
AB  - Loss of the proximal humerus following trauma or tumor ablation results in
      tremendous functional impairment because of the inability to position the hand in
      space. Although scapulohumeral athrodesis is described in the literature,
      insufficient follow-up has prevented full appreciation of functional outcome and
      patient satisfaction. This report describes favorable restoration of upper
      extremity function in two patients who sustained traumatic injuries to the
      proximal humerus following scapulohumeral arthrodesis In both cases, vascularized
      fibula transplantation and allograft bone were used, and pedicled latissimus
      muscle transfers were required for soft-tissue closure.

PMID- 10954314
TI  - Rectus abdominis free-tissue transfer in lower extremity reconstruction: review
      of 40 cases.
AB  - Forty patients who underwent rectus abdominis free-tissue transfer with split
      thickness skin grafts for reconstruction of the lower extremity are reported. The
      procedures were performed between January, 1992 and December, 1998. Transfers
      were utilized for coverage of acute soft-tissue and bone defects (18 patients),
      defects following radical debridement of chronic osteomyelitis of the leg and
      foot (13 patients) or diabetic foot ulcers (eight patients), and for unstable
      scars (one patient). At a mean follow-up of 3.6 years, there was no donor-site
      morbidity; there were seven local complications--five superficial flap necroses
      and two flap congestions. Three flaps were totally lost. All patients but one
      were ambulatory and fully weight-bearing at the time of review, with
      consolidation of the fractures and bone defects and no evidence of recurrence of
      infection in the osteomyelitis or diabetic foot ulcer groups. The relatively high
      success rate (92.5 percent), the ease of surgical dissection, the consistency and
      size of the deep inferior epigastric pedicle, the absence of donor-site
      morbidity, and relatively low complication rates make the rectus abdominis muscle
      one of the preferable free-tissue transfers for these authors.

PMID- 10954315
TI  - Reanimation of early facial paralysis with hypoglossal/facial end-to-side
      neurorrhaphy: a new approach.
AB  - The classic hypoglossal transfer to the facial nerve invariably results in
      profound functional deficits in speech, mastication, and swallowing, and causes
      synkinesis and involuntary movements in the facial muscles despite good
      reanimation. Techniques such as a hypoglossal/facial nerve interpositional jump
      graft and splitting the hypoglossal nerve cause poor functional results in facial
      reanimation and mild-to-moderate hemiglossal atrophy, respectively. Direct
      hypoglossal/facial nerve cross-over through end-to-side coaptation without
      tension was done in three fresh cadavers and four patients. The patients had
      facial paralysis for less than 7 months. Complete mobilization of the facial
      nerve trunk and its main branches beyond the pes anserinus from the stylomastoid
      foramen, division of the frontal branch, if necessary, and superior elevation of
      the hypoglossal nerve after dividing the descendens hypoglossi, thyrohyoidal
      branches, occipital artery, and retromandibular veins were performed. The end of
      the facial nerve was hooked up through both a quarter of a partial oblique
      neurotomy and a perineurial window at the side of the hypoglossal nerve.
      Temporalis muscle transfer to the eyelids and the first stage of cross-facial
      nerve transfer were performed simultaneously. None of the patients experienced
      hemiglossal atrophy, synkinesis, and involuntary movements of the facial muscles.
      Regarding facial reanimation, one patient had excellent, one patient good, and
      the others fair and poor results after a follow-up of at least 1 year.

PMID- 10954316
TI  - Microsurgical reconstruction for caustic injuries of the oral cavity and
      esophagus.
AB  - Ingestion of caustic material often produces profound and irreversible pathologic
      changes that require reconstructive surgery of the organs damaged. This report
      describes the authors' successful experience with microsurgical techniques that
      allowed adequate reconstruction in three patients with cicatricial contracture of
      the oral cavity and esophagus following ingestion of caustic substances. All
      patients had attempted suicide by ingesting liquid alkali. Patients #1 and #2
      complained of limited mouth opening and impaired tongue movement due to oral scar
      contracture. Contracture release in the first patient resulted in a defect from
      the anterior border of the mandible to the retromolar region. The defect was
      resurfaced with a 6 x 12 cm free forearm flap. Release of the scar contracture in
      the second patient resulted in a long, narrow, tortuous defect that was difficult
      to cover, even with a forearm flap, and a jejunal segment was microsurgically
      transferred as a patch graft to reconstruct the defect. Patient #3 had dysphagia
      due to stricture of the cervical portion of the esophagus. The defect after
      resection of the cervical portion was reconstructed by free jejunal
      interposition. Appropriately selected free-flap transfer in each case provided a
      satisfactory restoration of function of the oropharyngeal and digestive passages.

PMID- 10954317
TI  - Severe constricting ring syndrome: case report.
AB  - This report presents a case of a male newborn with a severe circumferential
      amniotic band, treated by single-stage excision of the ring, and microvascular
      venous anastomosis between the proximal and distal parts of the affected site. No
      complications were encountered. A microsurgical approach to improve the
      circulation may be useful in some cases.

PMID- 10954318
TI  - Technique for selective microangiography of skin flaps with high contrast and
      fine detail.
AB  - The technical factors of microangiography were studied, and the authors found
      that the main limiting factors in resolution were the injection pressure of the
      contrast medium and the thickness of the materials. A gentle manual hand pressure
      injection, with the aid of visual monitoring under the operating microscope, were
      keys to obtaining beautiful microangiograms.

PMID- 10954319
TI  - Use of the turnover epineurial sheath tube for repair of peripheral nerve gaps.
AB  - Autologous nerve grafting is the conventional technique for bridging nerve gaps,
      despite its various disadvantages. In this study, the authors investigated the
      effects of the turnover epineurial sheath tube (TEST) as an alternative to nerve
      grafting for the repair of nerve gaps, using a rat sciatic nerve model in four
      groups: Group 1 (n = 5): sham control; Group 2 (n = 10): segmental nerve
      resection + no repair; Group 3 (n = 10): segmental nerve resection + nerve
      grafting; Group 4 (n = 15): segmental nerve resection + TEST. Functional recovery
      was evaluated by walking-track analysis. The sciatic nerves and gastrocnemius
      muscles were harvested for histologic and quantitative histomorphometric
      evaluation at 12 weeks. Sciatic functional indices and histomorphometric analyses
      revealed statistically significant differences between the sham control and the
      three experimental groups (p < 0.001). The difference between the TEST group and
      the nerve graft group was not significant; however functional recovery was
      significantly improved in these two groups, compared to the non-repaired group (p
      < 0.05). The authors suggest that the TEST provides a suitable conduit between
      two stumps, eliminates donor-site morbidity, reduces the number of suture sites,
      fibrosis, and operating time, and might be an alternative to nerve grafting for
      nerve gap repair.

PMID- 10954320
TI  - Direct muscle neurotization in rat soleus muscle.
AB  - An experimental study was conducted using rat soleus muscles to characterize
      reinnervation of the denervated muscles by direct muscle neurotization. Also
      studied was whether there is any difference in the regeneration process between
      original (tibial) and foreign (peroneal) nerve neurotization. For functional
      evaluation, an electrophysiologic study was carried out by analyzing pattern,
      latency, amplitude, and duration of compound motor action potential. In a
      histochemical study, both hematoxylin-eosin stain and nicotineamide adenin
      dehydrogenase stain were used to identify the morphology and the change in the
      type of muscle fiber. Combined silver-acetylcholinesterase stain was utilized to
      identify reinnervated motor endplates and axonal sprouting. Evidence of
      regeneration of the denervated muscle by direct muscle neurotization could be
      confirmed. Regenerating muscles showed type grouping of muscle fibers. The newly
      formed ectopic motor endplate was connected with axonal sprouting. The giant
      motor endplate composed of mature axon sprouting and several new ectopic motor
      endplates appeared in the neurotization group. There was no specific difference
      in the regeneration process between original and foreign nerve neurotization.

PMID- 10954321
TI  - The multispecific organic anion transporter (OAT) family.
AB  - Organic anion transporters play important roles in the elimination of a variety
      of endogenous substances, xenobiotics and their metabolites from the body. During
      the last decade, molecular cloning has identified several families of
      multispecific organic anion transporters mediating the renal and hepatic
      elimination of organic anions and, most recently, the OAT (organic anion
      transporter) family, the founding member of which (OAT1) is the basolateral p
      aminohippurate (PAH) transporter in the renal proximal tubule. So far, four
      isoforms have been identified. OATs are membrane proteins with 12 putative
      membrane-spanning domains and function as sodium-independent exchangers or
      facilitators. OATs show weak structural similarity to organic cation transporters
      (OCTs) and OCTN/carnitine transporters. OATs are multispecific organic anion
      transporters, the substrates of which include both endogenous (e.g. cyclic
      nucleotides, prostaglandins, urate, dicarboxylates) and exogenous anions (various
      anionic drugs and environmental substances). All members of the OAT family are
      expressed in the kidney, while some are also expressed in the liver, brain and
      placenta. The OAT family represents the renal secretory pathway for organic
      anions and is also involved in the distribution of organic anions in the body.

PMID- 10954322
TI  - Ca2+ dynamics at the frog motor nerve terminal.
AB  - Rises in free [Ca2+]i in response to various tetanic stimuli (Ca2+ transient) in
      frog motor nerve terminals were measured by recording fluorescence changes of
      Ca2+ indicators and analyzed in relation to short-term synaptic plasticity. Ca2+
      transients reached a plateau after 10-20 impulses at 100 Hz and decayed in a
      three-exponential manner, in which the fast component was predominant. The
      plateau and fast component of the Ca2+ transient were elevated infralinearly with
      an increase in tetanus frequency. Computer simulation showed that the Ca2+
      transients estimated from fluorescence changes faithfully reflect the true
      changes in [Ca2+]i except for the initial 20 ms. A slow Ca2+ chelator, EGTA,
      loaded into the nerve terminal, decreased the magnitude of both the fast and slow
      components of facilitation of transmitter release and the time constant of the
      former. A fast Ca2+ chelator, BAPTA, decreased the magnitude of fast facilitation
      but slightly increased its time constant. These results suggest that Ca2+
      transients in the frog motor nerve terminals are primarily caused by Ca2+ entry
      and are dissipated by three components, in which the rate of the fast component
      is equivalent to that of free Ca2+ diffusion. The residual Ca2+ in the nerve
      terminals after stimulation accounts for the fast component of facilitation.

PMID- 10954323
TI  - Electrical properties of gap junction hemichannels identified in transfected HeLa
      cells.
AB  - Human HeLa cells transfected with mouse connexin Cx30, Cx46 or Cx50 were used to
      study the electrical properties of gap junction hemichannels. With no
      extracellular Ca2+, whole-cell recording revealed currents arising from
      hemichannels. Multichannel currents showed a time-dependent inactivation
      sensitive to voltage, Vm. Plots of the instantaneous conductance, ghc,inst,
      versus Vm were constant; plots of the steady-state conductance, ghc,ss, versus Vm
      were bell-shaped. Single-channel currents showed two conductances, gammahc,main
      and gammahc,residual, the latter approximately or approximately equals=1/6 of the
      former. Single-channel currents exhibited fast transitions (1-2 ms) between the
      main state and residual state. Late during wash-in and early during wash-out of 2
      mM heptanol, single-hemichannel currents showed slow transitions between an open
      state and closed state. The open channel probability, Po, was Vm-dependent. It
      declined from approximately =1 at Vm= 0 mV to 0 at large Vm of either polarity.
      Hemichannel currents showed a voltage-dependent gammahc,main, i.e., it
      increased/decreased with hyperpolarization/depolarization. Extrapolation to Vm=0
      mV led to a gammahc,main of 283, 250 and 352 pS for Cx30, Cx46 and Cx50,
      respectively. The hemichannels possess two gating mechanisms. Gating with
      positive voltage reflects Vj-gating of gap junction channels, gating with
      negative voltage reflects a property inherent to hemichannels, i.e., Vm or "loop"
      gating. We conclude that Cx30, Cx46 and Cx50 form voltage-sensitive hemichannels
      in single cells which are closed under physiological conditions.

PMID- 10954324
TI  - Inhibition of GABA(A) receptor (GABAR) currents by arachidonic acid in HEK 293
      cells stably transfected with alpha1beta2gamma2 GABAR subunits.
AB  - Agonist-stimulated liberation of arachidonic acid and subsequent generation of
      active metabolites are established components of several signal transduction
      pathways including pathways that regulate ion channels. We evaluated the role of
      arachidonic acid and some related unsaturated and saturated fatty acids in the
      modulation of a stably expressed recombinant gamma-aminobutyric acidA receptor
      (GABAR) isoform, the alpha1beta2gamma2 isoform. Whole-cell currents evoked by 10
      microM GABA were inhibited in a concentration-dependent manner by arachidonic
      acid (0.1-100 microM). This effect of arachidonic acid to inhibit GABAR currents
      was not reproduced by the non-metabolizable analog of arachidonic acid, 5,8,11,14
      eicosatetraynoic acid (ETYA) or by other monounsaturated or saturated fatty
      acids. However, another polyunsaturated fatty acid, linoleic acid, which is an
      essential fatty acid and an effective reductant like arachidonic acid, inhibited
      GABAR currents in a manner similar to arachidonic acid. Nordihydroguaiaretic acid
      (NDGA), indomethacin and 1-amonibenzotriazole (1-ABT) did not block the
      inhibitory effect of arachidonic acid, suggesting that arachidonic acid
      metabolites of the lipoxygenase, cyclooxygenase or P-450 pathways are unlikely to
      play a major role in the inhibitory effect of arachidonic acid on GABAR currents.
      However, the antioxidant N-acetyl cysteine (NAC), a scavenger of active oxygen
      radicals, reduced the inhibitory effect of arachidonic acid on GABAR currents
      significantly (P<0.01), suggesting that active oxygen radicals might mediate
      inhibition of GABAR currents by arachidonic acid.

PMID- 10954325
TI  - Projections and neurochemical coding of motor neurones to the circular and
      longitudinal muscle of the guinea pig gastric corpus.
AB  - The present study identified projection and neurochemical coding patterns of
      intrinsic circular (CMN) and longitudinal muscle motor neurones (LMN) in the
      guinea pig stomach by using the retrograde tracer DiI (1,1'-didodecyl-3,3,3',3'
      tetramethylindocarbocya-nine perchlorate) in combination with the
      immunohistochemical demonstration of choline acetyltransferase (ChAT), enkephalin
      (ENK), neuropeptide Y (NPY), nitric oxide synthase (NOS) and substance P (SP).
      Populations of LMN and CMN had similar neurochemical coding and a clear polarity
      of projection. Taking all DiI-labeled cell bodies as 100%, ascending pathways
      exhibited the coding ChAT/- (CMN:14.7%/LMN: 18.3%), ChAT/ENK (15.7%/10.1%),
      ChAT/SP/+/-ENK (19.2%/16.4%), or ChAT/NPY (4.4%/7.6%); descending pathways had
      the coding NOS/- (13.8%/16.9%), NOS/NPY (9.9%/17%), NOS/ENK (4.4%/1.2%) or
      NOS/NPY/ENK (13.0%/5.5%). The relative contributions of these populations were
      not different between CMN and LMN. However, target-specific projection patterns
      were revealed: most LMN (82%) had longitudinal whereas most CMN (58%) had
      circumferential projection preferences. The results indicate that gastric
      circular and longitudinal muscle layers are innervated by ascending excitatory
      and descending inhibitory pathways in the myenteric plexus. The projection
      patterns of CMN and LMN were different and followed the orientation of the muscle
      layers. It is suggested that the specific muscle motor pathways in the gastric
      myenteric plexus coordinate the reflex-mediated phasic and tonic activity of
      gastric muscle layers.

PMID- 10954326
TI  - Modulation of recombinant transient-receptor-potential-like (TRPL) channels by
      cytosolic Ca2+.
AB  - Whole-cell current recordings were used to examine the involvement of
      intracellular Ca2+ in the modulation of recombinant transient-receptor-potential
      like (TRPL) channels of Drosophila photoreceptor cells. TRPL was stably
      transfected in Chinese hamster ovary (CHO) cells and the expression of a
      calmodulin-binding protein with a molecular mass that corresponded to TRPL was
      demonstrated using calmodulin overlays. In cells expressing TRPL, ionic currents
      that were prominently outwardly rectifying were detected prior to activation of
      intracellular signalling pathways. The outwardly rectifying currents reversed
      close to 0 mV and did not occur after removal of permeant cations from the
      intracellular space. This suggests that TRPL forms non-selective cationic
      channels that appear to be constitutively active in mammalian cell lines. The
      TRPL channel currents were enhanced by manoeuvres that activate the phospholipase
      C (PLC) signalling pathway. These included activation of membrane receptors by
      thrombin, activation of G proteins by cell dialysis with guanosine 5'-O-(3
      thiotriphosphate) (GTP[gamma-S]) and release of Ca2+ from intracellular stores by
      dialysis with inositol 1,4,5-trisphosphate (IP3). After complete depletion of
      Ca2+ stores, IP3 had no effect on TRPL currents, suggesting that IP3 does not
      activate recombinant TRPL channels directly. However, thapsigargin, which induces
      a rise of cytosolic Ca2+, increased TRPL channel currents. Cell dialysis with
      solutions containing various concentrations of Ca2+ enhanced TRPL currents in a
      dose-dependent manner (EC50=450 nM Ca2+). Conversely, chelation of cytosolic Ca2+
      abolished TRPL channel currents. The present results indicate that the activity
      of recombinant TRPL channels expressed in mammalian cell lines is up-regulated by
      a rise of cytosolic Ca2+.

PMID- 10954327
TI  - Single-channel currents through transient-receptor-potential-like (TRPL)
      channels.
AB  - Single-channel current recordings were used to examine the properties and
      modulation of Drosophila transient-receptor-potential-like (TRPL) channels
      transiently expressed in HEK and COS cells. Recombinant TRPL channels were
      constitutively active and characterized by a conductance of 104 pS in on-cell
      membrane patches with 115 mM Na+ and 2 mM Mg2+ in the pipette solution. In inside
      out membrane patches exposed to 115 mM Na+ plus 2 mM Mg2+, 115 mM Na+ plus 10 mM
      Mg2+, 90 mM Ca2+ and 90 mM Ba2+ on both sides, the single-channel conductances
      were 72 pS, 36 pS, 48 pS and 46 pS, respectively. The single TRPL channel
      currents reversed close to 0 mV and displayed a linear voltage dependence between
      -120 mV and +120 mV. Removal of cations from the pipette and bath solutions
      abolished inward and outward currents, respectively. Similar currents were not
      observed in mock-transfected and native cells. The opening probability of TRPL
      channels increased by depolarizing the membrane and accounted for the outward
      rectification of whole-cell TRPL currents. In on-cell membrane patches, the TRPL
      channel activity was enhanced by cell dialysis of 300 microM guanosine 5'-O-(3
      thiotriphosphate) (GTP[gamma-S]) and by a rise of intracellular Ca2+ (>2 microM).
      Constitutively active TRPL channels depolarized the host cells to -10 mV and the
      membrane potential was restored by cell dialysis with 10 mM BAPTA. The present
      results suggest that TRPL forms non-selective cationic channels modulated by
      intracellular Ca2+ in mammalian cells.

PMID- 10954328
TI  - Hyperforin modulates gating of P-type Ca2+ current in cerebellar Purkinje
      neurons.
AB  - Whole-cell, patch-clamp recordings from acutely isolated cerebellar Purkinje
      neurons demonstrate a two-stage modulation of P-type high-voltage-activated (HVA)
      Ca2+ current by a constituent of St. John's wort, hyperforin (0.04-0.8 microM).
      The first stage of modulation was voltage dependent and reversible. It comprised
      slow-down of the activation kinetics and a shift in the voltage dependence of P
      current to more negative voltages. Hyperforin (0.8 microM) shifted the maximum of
      the current/voltage (I/V) relationship by -8+/-2 mV. The second, voltage
      independent stage of modulation was manifested as a slowly developing inhibition
      of P-current that could not be reversed within the period of study. Neither form
      of modulation was abolished by intracellular guanosine 5'-O-(2-thiodiphosphate)
      (GDPPS) or guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) or by strong
      depolarising pre-pulses, indicating that modulation via guanine nucleotide
      binding proteins (G proteins) is not involved in the observed phenomenon.
      Calmidazolium (0.5 microM), an antagonist of the intracellular Ca2+-binding
      protein calmodulin significantly inhibited the hyperforin-induced shift of the
      IIV curve maximum and the slow-down of the activation kinetics. It did not,
      however, affect the delayed inhibition of P-current, indicating that the two
      stages of modulation are mediated by separate mechanisms.

PMID- 10954329
TI  - Role of nitric oxide in the contraction of circular muscle in the rat portal
      vein.
AB  - The role of nitric oxide in the electrical and mechanical activities of the rat
      portal vein was examined in circular muscle preparations with intact endothelium
      that were isolated from the longitudinal muscle layer. In contrast to the
      longitudinal muscle preparation, the circular muscle preparation did not show
      spontaneous phasic contraction. Inhibition of nitric oxide synthesis by Nomega
      nitro-L-arginine (L-NNA) induced a tonic contraction. The contraction was
      inhibited by L-arginine, sodium nitroprusside or nifedipine. L-NNA did not induce
      contraction in endothelium-damaged preparations. The membrane potential of smooth
      muscle cells recorded in endothelium-intact preparations showed sporadic action
      potentials. L-NNA increased the frequency of action potentials without changing
      the resting membrane potential. The action potentials were inhibited by
      nifedipine. In the presence of L-NNA, sodium nitroprusside decreased the
      frequency of the action potentials without changing the resting membrane
      potential. These results indicated that contraction of rat portal vein circular
      muscles is inhibited tonically by nitric oxide, at least partly through
      inhibition of electrical activity.

PMID- 10954330
TI  - Lack of integrative control of heat production and heat loss after capsaicin
      administration.
AB  - Body temperature is usually regulated by opposing controls of heat production and
      heat loss. However, systemic administration of capsaicin activates heat loss and
      heat production simultaneously. Because capsaicin receptors are located mainly on
      primary sensory neurons and body temperature is regulated by the central nervous
      system, we investigated the brain mechanisms involved in these capsaicin-induced
      thermal responses. For this purpose, we examined the effects of spinalization and
      decerebration on these responses in artificially ventilated, urethane
      anesthetized rats. Cervical spinal transection largely attenuated both responses,
      showing the critical involvement of the brain. Colonic temperature (Tc) did not
      change after the capsaicin administration to the spinalized rats. Decerebration
      between the hypothalamus and midbrain prevented the capsaicin-induced heat loss
      and enhanced the capsaicin-induced heat production. Consequently, Tc increased
      without a hypothermic period. The results show that capsaicin activates brainstem
      controlled heat production and forebrain-controlled heat loss separately.

PMID- 10954331
TI  - Substance P and central respiratory activity: a comparative in vitro study in NK1
      receptor knockout and wild-type mice.
AB  - Neurokinin-1 receptors (NK1) are present within the respiratory medullary network
      and in the phrenic nucleus, which controls the diaphragm. We compared the
      efficacy of substance P (SP) at inducing changes in respiratory frequency or the
      amplitude of the respiratory motor output between NK1 knockout (NK1-/-) and wild
      type mice, using the in vitro brainstem-spinal cord preparation. The in vitro
      respiratory frequency, as well as the variability of the rhythm and the amplitude
      of the motor output were similar in both lines. In wild-type mice, application of
      exogenous SP induced either an increase in respiratory frequency (superfusion of
      the medulla) or an increase of the inspiratory motor output, as defined by the
      integral of C4 cervical ventral root activity (superfusion of the spinal cord).
      These two effects were not apparent in NK1-/- mice. In conclusion, NK1 receptors
      mediate the respiratory responses to SP but the lack of NK1 receptors in newborn
      NK1-/- mice does not change the respiratory activity.

PMID- 10954332
TI  - Modulation of low-threshold T-type calcium channels by the five muscarinic
      receptor subtypes in NIH 3T3 cells.
AB  - The modulation of a transient T-type calcium current by the five muscarinic
      receptor subtypes, stably expressed in NIH 3T3 cells, was studied with the whole
      cell patch-clamp technique. Voltage-step depolarizations applied to the NIH 3T3
      cells revealed a low-voltage-activated (LVA) T-type calcium current that was
      inhibited by Ni2+ and unaffected by omega-conotoxin GVIA. In cells transfected
      with the m3 and m5 muscarinic receptors, application of acetylcholine (ACh)
      resulted in a pertussis-toxin-insensitive increase in peak T-type calcium current
      amplitude. The m3-induced atropine-sensitive increase in current amplitude was
      accompanied by a shift in the voltage dependence of activation to more
      hyperpolarized potentials. The increase in peak T-type calcium current amplitude
      and the shift in voltage dependence was mimicked by incubation with 500 microM 8
      bromo-cAMP. Conversely, T-type calcium current amplitudes were reduced by
      incubation with 10 microM RpcAMPS, an inhibitor of cAMP-dependent protein kinase
      (PKA). Preincubation with 500 microM 8-bromo-cAMP or with 10 microM RpcAMPS
      abolished the increase in T-type calcium current amplitude previously noted on
      stimulation of the m3 muscarinic receptor by ACh. Application of ACh to NIH 3T3
      cells stably transformed with the m1 muscarinic receptor resulted in no
      discernable change in T-type calcium current amplitude. However, on pre
      incubation of the cells with calphostin C, an inhibitor of protein kinase C
      (PKC), application of ACh to the cells now resulted in a robust increase in T
      type calcium current amplitude. Application of 500 nM PDBu, an activator of PKC,
      reduced the T-type calcium current amplitude. No significant changes in T-type
      calcium currents were observed on application of ACh to cells stably transfected
      with the m2 or m4 muscarinic receptors. However, after pre-incubation with
      forskolin, the m2 muscarinic receptor induced a decrease in T-type calcium
      current amplitude. Stimulation of the ml, m3 and m5 muscarinic receptors in the
      NIH 3T3 cell resulted in dose-dependent increases in the concentration of
      intracellular cAMP in comparison to control as determined by cAMP immunoassay.
      Conversely, stimulation of the m2 and m4 muscarinic receptors by carbachol
      resulted in a dose-dependent reduction in intracellular concentrations of cAMP,
      as compared with control basal levels. It is concluded that the m3 and m5
      muscarinic receptors enhance T-type calcium channel activity. At least in the
      case of the m3 muscarinic receptor, the increased T-type channel activity
      appeared to be mediated via increased cAMP levels and subsequent activation of
      PKA. The lack of effect of the ml muscarinic receptor on the T-type calcium
      channel was probably due to the opposing actions of concomitant activation of
      both PKC and PKA. The physiological significance of these findings is discussed.

PMID- 10954333
TI  - Potassium-depolarization-induced cytoplasmic [Ca2+] transient in freshly
      dissociated pyramidal neurones of the rat dorsal cochlear nucleus.
AB  - The significance of voltage-activated Ca2+ currents in eliciting cytoplasmic Ca2+
      transients was studied in pyramidal neurones isolated from the rat dorsal
      cochlear nucleus using combined enzyme treatment/mechanical trituration.
      Increases in cytoplasmic Ca2+ concentration ([Ca2+]i) were evoked by K+-induced
      depolarizations (10-50 mM) and monitored by the Fura-2 fluorimetric technique.
      The acutely dissociated neurones had a resting [Ca2+]i of 17.2+/-0.5 nM. They
      possessed caffeine-sensitive Ca2+ stores which were empty at rest; these stores
      could be filled with Ca2+ entering from the extracellular space and were re
      emptied quickly. The effects of various specific high-voltage-activated (HVA)
      Ca2+ channel antagonists (nifedipine, omega-agatoxin IVA and omega-conotoxin
      GVIA) on [Ca2+]i transients were tested. Analysis of the blocking effects of
      these agents on the [Ca2+]i, transients indicates that, in the pyramidal neurones
      of the dorsal cochlear nucleus, N-type Ca2+ channels are primarily responsible
      for producing the depolarization-induced increases in [Ca2+]i.

PMID- 10954334
TI  - The relationship between hypotonically-induced taurine and K fluxes in trout red
      blood cells.
AB  - Hypotonic swelling of teleost erythrocytes activates multiple transport systems
      leading to the regulatory decrease of cell volume. We have examined using
      pharmacological manipulation the swelling-induced taurine flux pathway in red
      blood cells of the rainbow trout and its relationship to swelling-induced K flux
      pathways. We show that the activation and deactivation of taurine flux is rapid
      and that the flux is a sigmoidal function of cell volume. N-ethylmaleimide (NEM)
      and the non-specific protein kinase inhibitor, staurosporine, both inactivated
      the hypotonically-induced taurine flux with concentrations eliciting half-maximal
      inhibition (IC50s) of 212 and 17 micromol(-1), respectively. The low taurine
      fluxes under isotonic conditions were unaffected. By contrast, the tyrosine
      kinase inhibitor, genistein, partially inhibited taurine flux under both isotonic
      and hypotonic conditions. The specific phosphatase inhibitor, calyculin A, had no
      inhibitory or stimulatory effect under either condition whilst the less-specific
      phosphatase inhibitor, ortho-vanadate, reduced taurine flux only under hypotonic
      conditions. In these respects the regulatory control of the taurine pathway
      differs from the Cl-dependent K flux. However, NEM and staurosporine also
      inhibited the Cl-independent K flux, both with similar IC50s to those observed
      for taurine fluxes. This supports the idea of the hypotonically-induced taurine
      flux and the Cl-independent K flux sharing the same transport pathway.

PMID- 10954335
TI  - Effect of hypohydration on core temperature during exercise in temperate and hot
      environments.
AB  - The purpose of this study was to compare directly the physiological consequences
      of 5% hypohydration or euhydration during exercise in both temperate (23 degrees
      C) and hot (33 degrees C) environments. The subjects were eight male volunteers.
      Each performed four 1-h exercise bouts at 60% maximum oxygen uptake, one in each
      of the following conditions: hot-hypohydrated, hot-euhydrated, temperate
      hypohydrated, and temperate-euhydrated. Heart rate (HR), rectal temperature
      (Tre), forearm blood flow, and oxygen uptake were measured after 20, 40, and 60
      min exercise. Whole-body sweat rate was also determined for each exercise bout.
      Hypohydration increased Tre significantly (P<0.05) more in the hot environment
      (0.16 degrees C per 1% decrease in body mass) than in the temperate environment
      (0.08 degrees C per 1% hypohydration). Furthermore, compared with euhydration,
      hypohydration decreased forearm blood flow and whole-body sweat rate
      significantly more during exercise in the hot than in the temperate environment.
      The reductions in forearm blood flow and whole-body sweat rate appear to have
      decreased heat loss, thus accounting for the increase in Tre during exercise in
      the heat while hypohydrated. In conclusion, this study illustrates that the
      physiological consequences of hypohydration during exercise are exacerbated in
      the heat.

PMID- 10954337
TI  - Ca2+ uptake by the sarcoplasmic reticulum decreases the amplitude of
      depolarization-dependent [Ca2+]i transients in rat gastric myocytes.
AB  - Gastric myocytes loaded with fura-2 were voltage-clamped at -60 mV.
      Depolarizations to 0 mV evoked nifedipine-sensitive (5 microM) inward currents
      and Ca2+ transients. Cyclopiazonic acid (5 microM) elevated steady-state [Ca2+]i
      and reduced Ca current (ICa), but when divalent cations were omitted from the
      extracellular solution, cyclopiazonic acid had no effect on either the amplitude
      or the current-voltage relationship of the nifedipine-sensitive current. This
      suggests that the reduction in ICa was caused by the rise in steady-state
      [Ca2+]i. The relationship between the total Ca2+ influx carried by the Ca2+
      current (sigmaI(Ca).dt) and the amplitude of the Ca2+ transient (delta[Ca2+]i)
      was analysed for experiments using physiological Ca2+ solutions by calculating
      the ratio delta[Ca2+]i/sigmaI(Ca).dt. Cyclopiazonic acid (5 microM) and ryanodine
      (10 microM) both increased this ratio, indicating a decrease in the buffering
      power of the cell. Mimicking the increase in steady-state [Ca2+]i produced by
      these agents by changing the holding potential to -40 mV, however, did not affect
      delta[Ca2+]i/sigmaI(Ca).dt. It was concluded that up-take by a ryanodine
      sensitive store normally limits Ca2+ distribution to the bulk cytoplasm following
      entry to the cell through dihydropyridine-sensitive channels.

PMID- 10954336
TI  - Identification of molecular regions responsible for the membrane trafficking of
      Kir6.2.
AB  - The subunits of the pancreatic ATP-sensitive potassium channel Kir6.2 and the
      sulphonylurea receptor (SUR1) contain endoplasmic reticulum (ER) retention
      signals (RKR), which prevent their plasma membrane expression when expressed
      individually. When co-expressed, however, these signals are masked and the
      complex traffics to the plasma membrane. To investigate this further, we have
      expressed epitope-tagged chimaeras between Kir6.2 and Kir2.1 (which traffics to
      the membrane independently of SUR1) in Xenopus oocytes alone and together with
      SUR1. By staining sections of the oocytes, we show that, in addition to the ER
      retention signal present in the distal C-terminus, the M2 transmembrane and the
      proximal C-terminal regions also contribute to the inability of Kir6.2 to traffic
      to the membrane in the absence of SUR1. Furthermore, by staining the whole
      oocytes for the hexa-histidine tag attached to the N-terminus of SUR1, we provide
      direct experimental evidence that the N-terminus of SUR1 is extracellular.

PMID- 10954338
TI  - Gastrointestinal function, divalent metal transporter-1 expression and intestinal
      iron absorption.
AB  - Iron absorption involves two carriers, one involved in the uptake of iron across
      the microvillus membrane of the enterocyte and the other in its transfer to the
      plasma at the basolateral surface. The uptake phase is thought to involve
      divalent metal transporter-1 (DMT1) which may move from the cytoplasm to the
      microvillus membrane under conditions of iron deficiency. To examine this
      possibility we used fasted animals previously fed an iron-deficient diet and then
      gavaged with iron. We measured the processes of iron absorption using in vivo gut
      sacs and correlated the changes observed with the intensity of DMT1 staining and
      gene expression in the duodenum. Fasting resulted in increased iron absorption,
      whereas gavage with iron decreased absorption. These changes were due to
      alterations in the uptake phase of absorption but not the transfer phase. There
      was also a highly significant correlation between the reduction in iron
      absorption, microvillus DMT1 staining and messenger ribonucleic acid (mRNA)
      expression. The loss of DMT1 from the microvillus membrane was not associated
      with an increase in cytoplasmic staining, suggesting that its loss was due to
      destruction of the carrier protein. It is concluded that DMT1 functional activity
      is determined by de novo synthesis and that the latter is regulated post
      transcriptionally by enterocyte iron levels.

PMID- 10954339
TI  - Non lipid, dose-dependent effects of pravastatin treatment on hemostatic system
      and inflammatory response.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effects of
      pravastatin treatment on lipid, inflammation, and coagulation parameters in
      patients suffering from myocardial infarction with or without carotid
      atherosclerotic lesions (groups 1 and 2, respectively). METHODS: In the first
      phase of the study, a cross-sectional comparison of lipid, inflammation, and
      coagulation parameters was performed between the patients and the control group
      (group 3). Highly significant differences in these parameters were observed,
      especially in group 1. In the second phase of the study, we assessed the effects
      of a persistent reduction in cholesterol synthesis induced by increasing doses of
      pravastatin (20 mg daily for 8 weeks and 40 mg daily for a further 8 weeks). In
      addition to the well-established lipid-lowering effect, significant changes in
      inflammation and coagulation parameters were observed. In particular, pravastatin
      at a dosage of 20 mg/ day significantly reduced only fibrinogen levels, while at
      a dosage of 40 mg/day significantly reduced factor VII, fibrinogen, prothrombin
      fragments 1 and 2, thrombin-antithrombin complexes, tissue plasminogen activator
      antigen (tPA:Ag) before venous occlusion (b.o.), inhibitor of plasminogen
      activator activity (PAI) b.o., PAI activity after occlusion (a.o.), the human
      autoantibodies against oxidized low-density lipoprotein (LDL), and the c fraction
      of the third component system levels, and significantly increased tPA:Ag a.o.
      levels. RESULTS: Our results show that in patients suffering from myocardial
      infarction the risk of thrombotic complications can be decreased with
      pravastatin, especially by larger doses. However, the relationship must be
      further investigated because the observed reductions in the hemostatic system and
      inflammatory response seemed to be dose dependent, while the effects of
      pravastatin treatment were not significantly correlated with total and LDL
      cholesterol changes.

PMID- 10954340
TI  - Efficacy of activated charcoal versus gastric lavage half an hour after ingestion
      of moclobemide, temazepam, and verapamil.
AB  - OBJECTIVE: To compare the efficacy of activated charcoal and gastric lavage in
      preventing the absorption of moclobemide, temazepam, and verapamil 30 min after
      drug ingestion. METHODS: In this randomized cross-over study with three phases,
      nine healthy volunteers received a single oral dose of 150 mg moclobemide, 10 mg
      temazepam, and 80 mg verapamil after an overnight fast. Thirty minutes later,
      they were assigned to one of the following treatments: 25 g activated charcoal as
      a suspension in 200 ml water, gastric lavage (10x200 ml), or 200 ml water
      (control). Plasma concentrations of moclobemide, temazepam, and verapamil were
      determined up to 24 h. RESULTS: Activated charcoal reduced the area under the
      plasma concentration time curve from 0 h to 24 h (AUC0-24 h) of moclobemide and
      temazepam by 55% (P<0.05) and by 45% (P<0.05), respectively. The AUC0-24 h of
      verapamil was not significantly reduced by charcoal. Gastric lavage decreased the
      AUC0-24 h of moclobemide by 44% (P<0.05), but had no significant effect on that
      of temazepam or verapamil. The peak plasma concentration (Cmax) of moclobemide,
      temazepam, and verapamil was reduced by 40%, 29% (P<0.05), and 16%, respectively,
      by activated charcoal. Gastric lavage did not significantly decrease the Cmax of
      any of these drugs. CONCLUSION: The absorption of moclobemide, temazepam, and
      verapamil can be moderately reduced by activated charcoal given 30 min after drug
      ingestion, while gastric lavage seems to be less effective.

PMID- 10954341
TI  - A study of the pharmacokinetic interaction between lamivudine and alpha
      interferon.
AB  - OBJECTIVE: This study was designed to investigate any possible pharmacokinetic
      interaction between lamivudine and alpha interferon as potential candidates for
      combination therapy for the treatment of hepatitis B virus (HBV). METHODS:
      Nineteen healthy male, Caucasian volunteers, aged 20-41 years and weighing 60.5
      83.5 kg completed this open, non-randomised study. They each received a single,
      abdominal, deep s.c. injection of 10 mIU alpha interferon on day 1, followed by a
      wash-out period of at least 1 week. Subjects then began a 7-day course of
      lamivudine (100 mg) followed by a further 10-mIU alpha-interferon injection
      directly after oral lamivudine dosing. Blood and urine samples were taken pre-
      and post-dose for alpha-interferon and/or lamivudine assay. RESULTS: Lamivudine
      was safe and well tolerated in all subjects. No adverse events were reported in
      subjects on lamivudine, whereas 106 adverse events considered attributable to
      alpha interferon were recorded. Statistical analysis of pharmacokinetic
      parameters indicated no significant effect of lamivudine on alpha-interferon
      pharmacokinetics. There was a small statistically significant reduction
      (approximately 10%) in the area under the lamivudine concentration time curve on
      co-administration with alpha interferon and a concomitant increase in clearance,
      which is not considered clinically relevant. CONCLUSIONS: Alpha interferon and
      lamivudine can be co-administered with no requirement for dose modification, as
      there was no clinically significant difference in the pharmacokinetics of either
      drug.

PMID- 10954342
TI  - The effect of body weight on dalteparin pharmacokinetics. A preliminary study.
AB  - AIM: To investigate whether there were significant differences in the volume of
      distribution (V) and clearance (CL) of dalteparin in obese versus normal-weight
      patients, and thereby determine whether dosing of dalteparin should be based on
      total body weight, lean body weight or an adjusted body weight in obese patients.
      METHODS: Patients (ten obese and ten normal weight) treated with dalteparin were
      matched for age, gender, lean body weight and creatinine CL. Two steady-state
      plasma dalteparin concentrations were taken from each patient and assayed in
      duplicate. The pharmacokinetic values of V and CL were estimated, for each
      patient, using the Bayesian maximum a posteriori method with the program
      ABBOTTBASE. RESULTS: The mean V in obese patients was approximately 60% larger
      than in normal-weight patients, but this was not statistically significant (P =
      0.11; two-tailed). The mean value of V (8.41) in the normal-weight patients was
      similar to that reported in the literature. The mean difference in values of CL
      (18% larger in obese patients) was not clinically or statistically significant. A
      poor correlation was seen between V and lean body weight (r2 = 0.05). There was a
      moderate correlation between V and total body weight (r2 = 0.52) and between V
      and adjusted body weight (r2 = 0.55); adjusted body weight = [lean body weight +
      0.4(total body weight - lean body weight)]. Total body weight and adjusted body
      weight provided a better correlation with CL (r2 = 0.39, 0.32, respectively) than
      did lean body weight (r2 = 0.01). CONCLUSION: These results suggest that doses of
      dalteparin in obese patients should be based on total body weight or an adjusted
      body weight, but not lean body weight. This study highlights some potential
      differences in the pharmacokinetics of dalteparin in individuals who are obese,
      and further work is necessary to quantify these differences in more detail.

PMID- 10954343
TI  - Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of
      lamotrigine in healthy subjects.
AB  - OBJECTIVE: To study the effects of rifampicin, a potent inducer of the microsomal
      P450 enzyme system and of specific isoforms of the uridine 5'-diphosphate(UDP)
      glucuronyl-transferase enzyme system, and cimetidine, a known inhibitor of the
      hepatic microsomal cytochrome P450 enzyme system, on pharmacokinetics and
      pharmacodynamics of lamotrigine in healthy subjects. METHODS: Ten healthy male
      subjects received a single oral dose of 25 mg lamotrigine after a 5-day
      pretreatment with (1) cimetidine 800 mg divided into two equal doses, (2)
      rifampicin 600 mg, or (3) placebo. Serum and urine samples were analyzed using
      high-performance liquid chromatography. Changes in electroencephalographic (EEG)
      power were determined up to 48 h after lamotrigine administration. RESULTS: The
      values of the pharmacokinetic parameters of lamotrigine were: clearance over
      bioavailability (CL/F) 2.60+/-0.40 l/h, renal clearance (CLR) 0.10+/-0.03 l/h,
      terminal half-life (t1/2) 23.8+/-2.1 h, mean peak serum concentration (Cmax)
      0.29+/-0.02 microg/l, time to reach Cmax (tmax) 1.6+/-0.28 h, and total area
      under the serum concentration-time curve (AUC0-infinity) 703.99+/-82.31 microg/
      ml/min (mean +/- SEM). The amount of lamotrigine excreted as glucuronide was
      8.90+/-0.77 mg. Rifampicin significantly increased CL/F (5.13+/-1.05 l/h) and the
      amount of lamotrigine excreted as glucuronide (12.12+/-0.94 mg), whereas both
      t1/2 (14.1+/-1.7 h) and AUC(0-infinity) (396.24+/-60.18 microg/ml/min) were
      decreased (P<0.05). Cimetidine failed to affect pharmacokinetics of lamotrigine.
      Lamotrigine did not change EEG power. CONCLUSION: Rifampicin altered
      pharmacokinetics of lamotrigine due to induction of the hepatic enzymes
      responsible for glucuronidation, while coadministration of cimetidine to ongoing
      lamotrigine therapy has negligible effects on lamotrigine pharmacokinetics.
      Lamotrigine administered as a single dose of 25 mg has no effect on EEG power in
      healthy subjects.

PMID- 10954344
TI  - Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine.
AB  - OBJECTIVE: Several xenobiotics, including cocaine, are dosed by the nasal route
      for systemic effects. The aim of this study was to estimate and compare cocaine
      input into the systemic circulation after oral and nasal dosing, and to determine
      the relevance of local absorption through the nasal mucosa. METHODS: Cocaine was
      administered to healthy volunteers through the intravenous, oral, and nasal
      routes. Cocaine serum concentrations were measured at frequent intervals. From
      these data, the gastrointestinal, nasal, and nasal mucosa input rate functions
      were determined using nonparametric, subject-specific population deconvolution.
      RESULTS: After oral dosing, cocaine input into systemic circulation increased
      slowly and peaked around 45 min after ingestion. The median systemic
      bioavailability after oral dosing was 33%. After nasal dosing, drug input was
      substantial even during the first minute and showed two peaks at 10 min and 45
      min after ingestion. Since the second peak after nasal dosing closely resembled
      drug input after oral administration, we hypothesized that, after nasal
      administration, a part of the dose is swallowed and thereafter absorbed
      gastrointestinally. The data from the sessions with nasal cocaine administration
      were reanalyzed assuming the same shape for gastrointestinal drug input as after
      oral dosing. The fraction absorbed through the nasal mucosa was estimated to be
      19% (95% CI: 11-26%). The fraction absorbed through the nasal mucosa contributed
      31% (95% CI: 23-37%) of total systemic cocaine exposure. CONCLUSIONS: Our data
      suggest that the main reason addicts prefer nasal to oral cocaine dosing is
      faster absorption, enhancing the subjective effects rather than higher
      bioavailability.

PMID- 10954345
TI  - The relationship between age, gender, well-being and symptoms, and the use of
      pharmaceuticals, herbal medicines and self-care products in a Swedish
      municipality.
AB  - BACKGROUND: A relatively small proportion of the population accounts for a
      substantial part of the public drug cost. Therefore, identifying the
      characteristics of high users of drugs is an important step towards limiting the
      cost of drugs. The aim of this study was to assess the relationship between age,
      gender, well-being and symptoms, and the use of pharmaceutical specialities,
      herbal medicines and self-care products. METHODS: A postal questionnaire was sent
      to a representative population sample (n = 1.312) from a small Swedish
      municipality. The relationship between age, gender, well-being and symptoms, and
      the use of drugs and self-care products was tested using multivariate analysis.
      RESULTS: The questionnaire was answered by 827 subjects. The use of prescribed
      pharmaceuticals increased with age in both genders. Women used prescribed and non
      prescribed pharmaceuticals as well as herbal medicines and self-care products
      more than men. Subjects who reported low scores for well-being had significantly
      higher odds of having used prescribed pharmaceuticals than subjects with high
      scores. Bad perceived health was the only well-being measure that was associated
      with high odds for the use of herbal medicines. Most symptoms occurred more
      frequently in users than in nonusers of pharmaceuticals. Subjects with many
      symptoms (six or more) had higher odds of having used pharmaceuticals and self
      care products than those with few symptoms. CONCLUSION: High age, female gender
      and low perceived well-being significantly increased the use of drugs,
      particularly prescribed pharmaceuticals. Subjects with many symptoms used
      pharmaceuticals and self-care products more than those with few symptoms.

PMID- 10954346
TI  - Cyclical etidronate use is not associated with symptoms of peptic ulcer disease.
AB  - OBJECTIVE: To investigate whether the alkylbisphosphonate etidronate is
      associated with an increased risk of gastrointestinal symptoms. METHODS: We
      conducted an observational follow-up study on a possible relationship between
      etidronate use and the risk of gastrointestinal symptoms in a cohort of 2754
      women over 50 years of age. The study was performed with data on drug
      prescriptions obtained from the PHARMO database in the Netherlands. Women were
      included when they used either cyclical etidronate (n = 1050) or estrogen (n =
      1704) for at least 14 days. They were followed-up for incident use of antiulcer
      drugs while on exposure medication. RESULTS: The mean ages were 72 years and 59
      years in the etidronate and estrogen groups, respectively. In total, there were
      95 women with incident prescriptions for gastrointestinal events after a median
      duration of follow-up of 2.7 months (range 0.1-19.4 months). The crude relative
      risk of a gastrointestinal event for etidronate compared with estrogen use was
      1.2 [95% confidence interval (95% CI) 0.8-1.8]. Adjusted for baseline age, use of
      corticosteroids, salicylates and nonsteroidal anti-inflammatory drugs, the
      relative risk reversed to 0.6 (95% CI 0.4-1.2). CONCLUSION: The use of cyclical
      etidronate is not associated with an elevated risk of symptoms of peptic ulcer
      disease.

PMID- 10954347
TI  - Drug use in pregnancy among Italian women.
AB  - OBJECTIVE: To describe the use of drugs among Italian women during pregnancy and
      to compare it with other reports in Italy from the last 10 years. METHODS: A
      random sample of women who delivered in 1995-1996 were interviewed with regard to
      the care they received during pregnancy, delivery and the post-natal period.
      Information on antenatal care included maternal reports on the use of drugs
      during pregnancy. RESULTS: Of the 9004 women interviewed, 75% took at least one
      drug during pregnancy. Users took a median number of two drugs. Iron (51%) and
      vitamins (25%) dominate prescriptions throughout pregnancy. Fifteen percent of
      women reported treatment for threatened abortion and 27% for risk of pre-term
      delivery. The data do not differ from the drug exposure profile during pregnancy
      reported in other Italian studies. Logistic regression analysis of drug use
      (excluding haematologicals and nutritionals) shows an increased risk of usage for
      older women, the better educated, for those who reported health problems and
      those who had compulsory bed rest and/or hospitalisation during pregnancy.
      CONCLUSION: Seventy-five percent of the women reported use of at least one drug
      during pregnancy. Haematological and nutritional drugs are over prescribed.
      Although hormones have been clearly proven to be ineffective in preventing
      threatened abortion, the study shows an almost unchanged and out of date
      prescription pattern of progestational drugs. In order to avoid unnecessary
      exposure to potential risk, maternity care procedures should be reviewed and
      strictly related to an "evidence-based" approach.

PMID- 10954348
TI  - Effect of hospitalisation on liver enzymes in healthy subjects.
AB  - OBJECTIVES: The aims of the present evaluation were to determine whether the
      elevations in liver enzymes observed in phase-I trials are more common in
      subjects being hospitalised than in ambulatory subjects and to assess the
      relevance of these elevations. We therefore investigated the effect of
      hospitalisation on liver enzyme levels in subjects of all phase-I trials of
      sufficient length performed at the two Human Pharmacology Centres of Boehringer
      Ingelheim, located in Biberach and Ingelheim, Germany, over a 10-year period.
      METHODS: The evaluation was based on 29 phase-I trials conducted between 1987 and
      1996. These trials consisted of at least 4 days of observation of 220 subjects on
      placebo treatment in 273 trial participations. The mean changes (transformed into
      reference ranges) in the liver enzymes alkaline phosphatase, gamma glutamyl
      transpeptidase, aspartate aminotransferase, alanine aminotransferase and the
      AST/ALT ratio of hospitalised subjects were compared with those of ambulatory
      subjects. RESULTS: A small but statistically significant increase in the mean of
      the parameters GGT, AST and ALT during phase-I trials was observed in
      hospitalised subjects compared with ambulatory subjects. The increases were: 8%
      of the reference range width for GGT, 8% for AST and 17% for the ALT, although
      the differences were small in absolute terms. A relevant increase (defined as an
      increase to above the reference range or by at least 50% of the reference range)
      was more common in hospitalised subjects. CONCLUSION: Hospitalisation, although
      it is believed to protect subjects from confounding environmental factors, can
      itself be associated with increases in liver enzyme levels. The definition of a
      relevant increase can be used to identify subjects who need further evaluation.
      The cause of the increase in liver enzyme levels remains unclear.

PMID- 10954349
TI  - The relationship between risk of hypoglycemia and use of cibenzoline and
      disopyramide.
AB  - OBJECTIVE: A case-control study was carried out to compare the risks of
      hypoglycemia caused by disopyramide and cibenzoline. METHODS: We selected 91
      subjects with hypoglycemia from among 14,156 outpatients who consulted the
      National Cardiovascular Center (NCVC) and received drug therapy between September
      1997 and February 1998. We used the fasting blood sugar (FBS) level of 75 mg/dl
      or less as the cut-off level to screen for hypoglycemia. For each case, five
      controls matched for gender and age were selected from the clinical division
      consulted by relevant subjects. RESULTS: Ninety-one cases and 455 controls were
      enrolled in this study. Of 91 cases with hypoglycemia, 8 (8.8%) were treated with
      cibenzoline and 3 (3.3%) with disopyramide. The percentage of cases treated with
      cibenzoline was greater than that in the controls (1.5%), and the prescription
      frequency of cibenzoline during the study period was 2%. With adjustment for
      potential confounding factors using conditional logistic regression, hypoglycemia
      was significantly correlated with the use of cibenzoline [OR 8.0 (95% CI 1.7
      36.8)], insulin [OR 48.4 (95% CI 8.8-267.2)], and thyroid agents [OR 13.0 (95% CI
      1.1-160.4)]. An increased risk of hypoglycemia associated with the use of
      sulfonylureas was not detected. In additional logistic regression analysis,
      including the variables with individual sulfonylureas, glibenclamide but not
      gliclazide significantly increased the risk of hypoglycemia. The use of
      disopyramide did not affect the risk of hypoglycemia. In separate analyses for
      diabetic and non-diabetic patients, the risks of hypoglycemia associated with the
      use of drugs other than beta-blocking agents in non-diabetic patients were
      estimated to be lower than those in diabetic patients. CONCLUSION: The use of
      cibenzoline was significantly correlated with an increased risk of hypoglycemia.

PMID- 10954350
TI  - Methylation of 6-mercaptopurine and 6-thioguanine by thiopurine S
      methyltransferase. A comparison of activity in red blood cell samples of 199
      blood donors.
AB  - OBJECTIVES: To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as
      substrates for the methylation reaction catalysed by the enzyme thiopurine S
      methyltransferase (TPMT). METHODS: TPMT activity in haemolysed red blood cells of
      healthy blood donors was determined twice, using the same experimental setting
      and equal molar concentrations of 6-TG and 6-MP as substrates. After extraction,
      the reaction products 6-methyl-TG and 6-methyl-MP were quantified using specific
      high-performance liquid chromatography procedures. RESULTS: The medians of the
      TPMT activities from 199 blood donors were 54.4 nmol 6-MTG g(-1)Hb h(-1) when
      measured with 6-TG as the substrate and 35.8 nmol 6-MMP g(-1) Hb h(-1) when
      measured with 6-MP. The correlation coefficient for the 199 pairs of values was
      0.8695. On average, TPMT activity was 34% lower with 6-MP as substrate than with
      6-TG as substrate.

PMID- 10954351
TI  - Plasma levels of clozapine and desmethylclozapine are unaffected by concomitant
      ingestion of grapefruit juice.

PMID- 10954352
TI  - August 2000: medical conditions in the aircraft.

PMID- 10954353
TI  - Cabin environment and perception of cabin air quality among commercial aircrew.
AB  - OBJECTIVE: Our objective was to study the perception of cabin air quality (CAQ)
      and cabin environment (CE) among commercial cabin crew, and to measure different
      aspects of CAQ on intercontinental flights. METHODS: A standardized questionnaire
      was mailed in February-March 1997 to all Stockholm-based aircrew on duty in a
      Scandinavian flight company (n = 1,857), and office workers from the same company
      (n = 218). The answers were compared with an external reference group for the
      questionnaire (MM 040 NA). During this time, smoking was allowed on
      intercontinental flights, but not on other shorter flights. Smoking was
      prohibited on all flights after 1 September 1997. The participation rate was 81%
      (n = 1,513) in the aircrew, and 77% (n = 168) in the office group. Air humidity,
      temperature, carbon dioxide (CO2) and respirable dust were measured during
      intercontinental flights, during both smoking and nonsmoking conditions.
      Statistical analysis was performed by multiple logistic regression analysis,
      keeping age, gender, smoking, current smoking, occupation, and perceived
      psychosocial work environment simultanously in the model. RESULTS: Air humidity
      was very low (mean 5%) during intercontinental flights. In most cases (97%) the
      CO2 concentration was below 1,000 ppm. The average concentration of respirable
      particles was 67 microg x m during smoking conditions, and 4 microg x m(-3)
      during non-smoking conditions. Complaints of draftiness, too high temperature,
      varying temperature, stuffy air, dry air, static electricity, noise, inadequate
      illumination, and dust were more common among aircrew as compared with office
      workers from the same company. Female crew had more complaints on too low
      temperature, dry air, and dust. Current smokers had less complaints on stuffy air
      and environmental tobacco smoke (ETS). Younger subjects and those with atopy
      (childhood eczema, allergy to tree or grass pollen, or furry animals) reported
      more complaints. Reports on work stress and lack of influence on working
      conditions were strongly related to perception of a poor cabin environment.
      Flight deck crew had more complaints about inadequate illumination and dust, but
      less complaints about other aspects of the cabin environment, as compared with
      flight attendants. Aircrew who had been on a flight the previous week, where
      smoking was allowed, had more complaints on dry air and ETS. CONCLUSION:
      Complaints about work environment seems to be more common among aircrew than
      office workers, particularly draft, stuffy air, dry air, static electricity,
      noise, inadequate illumination and dust. We could identify personal factors of
      importance, and certain conditions that could be improved, to achieve a better
      perception of the cabin environment. Important factors were work stress, lack of
      influence on the working conditions, and environmental tobacco smoke on some
      longer flights. The hygienic measurements in the cabin, performed only on
      intercontinental smoking flights, showed that air humidity is very low onboard,
      and tobacco-smoking onboard leads to significant pollution from respirable dust.

PMID- 10954354
TI  - Nonsustained ventricular tachycardia in 193 U.S. military aviators: long-term
      follow-up.
AB  - BACKGROUND: Despite its importance to the aeromedical community, the occupational
      implications of asymptomatic, nonsustained ventricular tachycardia (VT) are not
      well described. We sought to clarify this issue via a review of military aviators
      evaluated for nonsustained VT by defining event rates for sudden cardiac death,
      syncope, presyncope and sustained VT, and by determining whether any cofactors
      predicted a subgroup at increased risk for such outcomes. METHODS: We reviewed
      the records of 193 military aviators evaluated at the U.S. Air Force Aeromedical
      Consultation Service for nonsustained VT from September 1960 to December 1992.
      Follow-up information was available on 192 of the 193 aviators over a mean of
      10.6 yr. Cofactor analysis focused on idiopathic VT (no associated underlying
      cardiac disease) and VT associated with mitral valve prolapse (MVP). RESULTS:
      There was no documented sustained VT; 9 (4.6%) had events including syncope (1),
      presyncope (5) and sudden death (3). Of these 9, 4 had idiopathic VT. The 3
      deaths were associated with coronary artery disease, MVP and cardiomyopathy. No
      cofactors predicted events in aviators initially presenting with asymptomatic
      nonsustained VT. For asymptomatic nonsustained VT, the maximum predicted annual
      event rate was 0.33% for idiopathic VT and 2.3% for VT with MVP (95% confidence
      limit). CONCLUSIONS: Nonsustained VT did not predict future documented sustained
      VT. Cofactors failed to predict a subgroup at increased risk for events.
      Idiopathic nonsustained VT appeared to be a low risk population for whom expanded
      waiver criteria are proposed with suggested limits on duration and number of
      episodes of VT.

PMID- 10954355
TI  - Effect of normobaric hypoxia on auditory sensitivity.
AB  - Previous psychophysical studies of hypoxia's effects on auditory sensitivity have
      provided mixed results but the weight of evidence supports the conclusion that
      sensitivity is unaffected by hypoxia. This conclusion is discrepant with that
      drawn from physiological studies in which hypoxia has been found to affect
      auditory-evoked response (AER) latency. One possible explanation of this
      discrepancy concerns the relatively low maximum frequency (8 kHz) for which
      hypoxia's effects were assessed in the psychophysical studies. We have extended
      the range of frequencies over which hypoxia's effects have been examined to
      include frequencies up to 16 kHz. Thresholds for 1-, 8-, 10-, 12-, 14- and 16-kHz
      tones were measured at levels of hypoxia equivalent to altitudes of 0, 1,200,
      2,400 and 3,700 m. Our results indicate that sensitivity for frequencies up to 16
      kHz is unaffected by hypoxia. We suggest that AER latency does not provide a
      valid measure of auditory sensitivity.

PMID- 10954356
TI  - Aircraft control forces and EMG activity: comparison of novice and experienced
      pilots during simulated rolls, loops and turns.
AB  - BACKGROUND: Flying an aircraft requires a considerable degree of coordination,
      particularly during aerobatic activities such as rolls, loops and turns. Only one
      previous study has examined the magnitude of muscle activity required to fly an
      aircraft, and that was restricted to takeoff and landing maneuvers. The aim of
      this study was to examine the phasing of muscle activation and control forces of
      novice and experienced pilots during more complex simulated flight maneuvers.
      METHODS: There were 12 experienced and 9 novice pilots who were tested on an
      Aermacchi flight simulator while performing a randomized set of rolling, looping,
      and turning maneuvers. Four different runaway trim settings were used to increase
      the difficulty of the turns (elevator-up, elevator-down, aileron-left, and
      aileron-right). Variables recorded included aircraft attitude, pilot applied
      forces, and electromyographic (EMG) activity. Discriminant function analysis was
      used to distinguish between novice and experienced pilots. RESULTS: Over all
      maneuvers, 70% of pilots were correctly classified as novice or experienced.
      Better levels of classification were achieved when maneuvers were analyzed
      individually (67-91%), although the maneuvers that required the greatest force
      application, elevator-up turns, were unable to discriminate between novice and
      experienced pilots. There were no differences in the phasing of muscle activity
      between experienced and novice pilots. The only consistent difference in EMG
      activity between novice and experienced pilots was the reduced EMG activity in
      the wrist extensors of experienced pilots (p < 0.05). The increased wrist
      extensor activity of the novice pilots is indicative of a distal control
      strategy, whereby distal muscles with smaller motor units are used to perform a
      task that requires precise control. Muscle activity sensors could be used to
      detect the onset of high G maneuvers prior to any change in aircraft attitude and
      control G-suit inflation accordingly.

PMID- 10954357
TI  - Aircraft control forces and EMG activity in a UH-1H Iroquois helicopter during
      emergency maneuvers.
AB  - BACKGROUND: Some air forces are concerned with the adequacy of existing pilot
      selection standards in respect to pilot strength. Some studies have provided
      evidence that a large number of pilots may not be able to match the control force
      levels specified in both military and civilian aircraft design standards.
      However, both sets of design standards have been based on the subjective comments
      of test pilots and may not, therefore, be applicable for the majority of pilots.
      The aim of this study was to quantify aircraft control forces during emergency
      maneuvers in an Iroquois helicopter and compare these forces with design
      standards. The examination of muscle activation patterns of pilots during
      maneuvers, when normalized, can provide additional information on the relative
      activation levels that pilots are using to produce the aircraft control forces.
      METHODS: Six pilots were tested in a UH-1 H Iroquois helicopter. The maneuvers
      were three engine-out landings and a hydraulics-off landing. The variables
      recorded were pilot applied forces and EMG activity. Multivariate analysis of
      variance was used to test for differences between maneuvers. RESULTS: The
      greatest cyclic and upward collective control forces were observed during
      constant attitude and variable flare engine-out landings. The greatest downward
      collective forces were observed during hydraulics-off landing. Greater levels of
      muscle activation were consistently observed during hydraulics-off landing than
      during the engine-out landings. Control forces consistently exceeded military
      design standards for cyclic and collective controls, however muscle activity
      levels were sub-maximal for all maneuvers. CONCLUSION: Comparisons between
      existing aircraft control-force design standards and pilot strength may
      overestimate the number of pilots who are able to produce sufficient force to fly
      the aircraft. Despite the high control forces observed, all pilots tested were
      able to successfully maneuver the helicopter without requiring a maximal muscular
      effort.

PMID- 10954358
TI  - The opto-kinetic cervical reflex during formation flight.
AB  - BACKGROUND: Weather formation flight is a difficult task prone to episodes of
      spatial disorientation. Therefore, investigation of sensory reflexes under these
      conditions is critical. Recent studies have shown that the opto-kinetic cervical
      reflex (OKCR) occurs during VMC flight conditions and serves to establish the
      horizon retinal image as a stabilized primary visual-spatial cue. The purpose of
      this research was to investigate the OKCR and field of view (FOV) during
      formation flight under VMC and IMC. HYPOTHESES: During VMC tasks pilots will
      align their heads with the visible horizon, but not under IMC. As FOV is
      decreased, there will be a significant reduction in OKCR-induced head movement.
      METHODS: There were 2 experiments conducted in which a total of 26 pilots
      completed simulated flight tasks in a stationary dome. Head tilt was examined as
      a function of aircraft bank with unrestricted FOV in Experiment I. Experiment II
      examined head tilt under three FOV conditions (40 degrees , 60 degrees and 100
      approximately circular). RESULTS: During VMC maneuvers pilots exhibited
      significant OKCR. There were no differences in head tilt between Solo Figure 8
      and Formation Figure 8 VMC conditions. Pilots did not tilt their heads under IMC
      Formation Flight. FOV did not significantly affect the OKCR. CONCLUSIONS: Pilots
      exhibit the OKCR during Formation and Solo VMC tasks. However, the OKCR is
      reduced when compared with low level navigation tasks, indicating a difference in
      the visual cues between tasks. Pilots do not exhibit OKCR during IMC flight;
      therefore, the OKCR will have an impact on formation flights in and out of clouds
      leading to sensory conflicts caused by repeated realignment of visual and
      vestibular systems.

PMID- 10954359
TI  - Test and evaluation of exercise-enhanced preoxygenation in U-2 operations.
AB  - BACKGROUND: Preoxygenation to prevent decompression sickness (DCS) during U-2
      reconnaissance flights requires considerable time and occasionally does not
      provide adequate protection. Increasing preoxygenation within a practical period
      of time provides marginally increased protection and is not always operationally
      feasible. Including exercise during preoxygenation to increase muscle tissue
      perfusion, cardiac output, and ventilation can improve the quality of the
      denitrogenation. METHODS: A pilot, who reported two cases of DCS during his first
      25 U-2 high flights involving cabin altitudes of 29,000-30,000 ft, volunteered to
      test exercise-enhanced preoxygenation. He performed 10 min of strenuous upper and
      lower body exercise at the beginning of preoxygenation prior to subsequent high
      flights without increasing total preoxygenation time. RESULTS: The exercise was
      performed at 75% of maximal oxygen uptake based on the estimated maximal oxygen
      uptake determined during an Air Force aerobic fitness test and heart rate. The
      pilot's next 36 high flights, using exercise-enhanced preoxygenation, were
      completed with no reports of DCS. CONCLUSIONS: This statistically significant
      operational test reinforced the laboratory studies. Implementation of this
      procedure for reducing DCS in susceptible U-2 pilots and collecting additional
      data from the U-2 pilot population is recommended.

PMID- 10954361
TI  - Inflight medical emergencies.
AB  - This report responds to resolutions asking the American Medical Association (AMA)
      to develop recommendations for the use of medical equipment and technology
      onboard commercial airlines. Information for the report was derived from a search
      of the MEDLINE database and references listed in pertinent articles, as well as
      through communications with experts in aerospace and emergency medicine. Based on
      this information, the AMA Council on Scientific Affairs determined that, while
      inflight morbidity and mortality are uncommon, serious events do occur, which
      require immediate emergency care. Management of serious problems requires an
      integrated emergency response system that ensures rapid notification of medical
      personnel on the ground, assistance from appropriately trained flight crews and
      passenger volunteers (if available), and adequate medical supplies and equipment
      to stabilize the victim. Physicians have an important role in the preflight
      evaluation and counseling of potential passengers who are at risk of inflight
      medical complications, and in providing inflight medical assistance. Some U.S.
      and foreign air carriers are upgrading inflight emergency medical kits and
      placing automated external defibrillators aboard aircraft. Few data are available
      regarding the effectiveness of such improvements in improving health or survival
      outcomes. Recent federal legislation requires assessment of the extent of
      inflight medical emergencies, including the adequacy of emergency medical
      supplies and equipment carried onboard commercial airliners. This legislation
      also should alleviate liability concerns by providing immunity for physicians and
      others who render inflight medical assistance.

PMID- 10954360
TI  - Medical oxygen and air travel.
AB  - This report responds to a resolution that asked the American Medical Association
      (AMA) to take action to improve airport and airline accommodations for passengers
      requiring medical oxygen. Information for the report was derived from a search of
      the MEDLINE database and references listed in pertinent articles, as well as
      through communications with experts in aerospace and emergency medicine. Based on
      this information, the AMA Council on Scientific Affairs determined that
      commercial air travel exposes passengers to altitude-related hypoxia and gas
      expansion, which may cause some passengers to experience significant symptoms and
      medical complications during flight. Medical guidelines are available to help
      physicians evaluate and counsel potential passengers who are at increased risk of
      inflight hypoxemia. Supplemental oxygen may be needed for some passengers to
      maintain adequate tissue oxygenation and prevent hypoxemic complications. For
      safety and security reasons, federal regulations prohibit travelers from using
      their own portable oxygen system onboard commercial aircraft. Many U.S. airlines
      supply medical oxygen for use during flight but policies and procedures vary.
      Oxygen-dependent passengers must make additional arrangements for the use of
      supplemental oxygen in airports. Uniform standards are needed to specify
      procedures and equipment for the use of medical oxygen in airports and aboard
      commercial aircraft. Revision of federal regulations should be considered to
      accommodate oxygen-dependent passengers and permit them to have an uninterrupted
      source of oxygen from departure to destination.

PMID- 10954363
TI  - The sleep inertia phenomenon during the sleep-wake transition: theoretical and
      operational issues.
AB  - Sleep inertia (SI) defines a period of transitory hypovigilance, confusion,
      disorientation of behavior and impaired cognitive and sensory-motor performance
      that immediately follows awakening. SI, the cognitive and behavioral correlate of
      the transition from sleep to wakefulness, has been incorporated in several models
      of sleep and vigilance regulation. Monitoring of several physiological parameters
      during the awakening period clearly indicate that this transition process is very
      slow. On the cognitive and behavioral side, SI has relevant operational
      implications. SI is one of the most serious contraindications to the use of
      napping during quasi-continuous operations if the individual may be required to
      perform complex tasks immediately after sudden awakening at unpredictable times.
      The studies on SI modulating factors showed that SI is strongly affected by slow
      wave sleep amount and sleep depth, while the outcomes concerning the modulation
      of SI by circadian factors are not consistent. Cognitive tasks involving high
      attentional load seem to be much more affected by SI than simple motor ones,
      performance accuracy being more impaired than speed. Finally, some possible
      countermeasures against the detrimental effects of SI to be applied in
      operational settings have been provided.

PMID- 10954362
TI  - Air transport of passengers of advanced gestational age.
AB  - Many airlines and defense forces have policies relating to the routine air
      transport of pregnant females in advanced stages of gestation. These vary, but on
      average flying is discouraged once gestational age reaches 32 to 38 wk. These
      recommendations probably evolved out of historical conservatism and anecdotal
      inflight events. Review of the literature and the basic physiology involved
      suggests that air transport, both rotary wing and fixed wing, does not predispose
      to either an increase in or acceleration of obstetric events. In fact, the
      literature strongly suggests that air transport is frequently extremely valuable
      in obstetric emergencies, and has no impact in advanced uncomplicated pregnancy.
      It is concluded that obstetric cases can be safely transported at any gestational
      age.

PMID- 10954364
TI  - Delayed onset pulmonary barotrauma or decompression sickness? A case report of
      decompression-related disorder.
AB  - A-24-yr-old male professional diver began to complain of substernal pain 3 h
      after a controlled ascent from a dive of less than 40 ft of sea water (fsw). The
      diving master who supervised his dive and the physicians who examined him on
      presentation suspected pulmonary barotrauma rather than decompression sickness
      (DCS) because he had only descended to a depth of 32 fsw. Hyperbaric oxygen
      therapy (HBO) by U.S. Navy treatment Table VI was implemented because of his
      progressively worsening pain. HBO was apparently effective and a relapse was not
      seen. The author cannot label his condition based on the conventional
      classification categories, such as decompression sickness (DCS), barotrauma or
      even decompression illness. This case report is offered as a topic for
      consideration in the controversy over decompression-related disorders.

PMID- 10954365
TI  - The role of the flight surgeon in Greece.
AB  - From 1915 [corrected], the first time a flight surgeon participated in an
      aeromedical evacuation, to the present, the role has become more fundamental by
      working in wars and operations, experiencing search and rescue aeromedical
      evacuations from mass accidents or motor accidents, treating seriously ill
      individuals, and caring for wounded victims of attacks either at the scene or at
      the hospital. The improvements in cognitive and technological standards of
      medical science and in the education available have contributed in upgrading the
      role of flight surgeons; however, their presence in flight is considered
      essential in 20-60% of aeromedical evacuations, with the remainder of the flights
      being covered by paramedical personnel. In the Greek territory, the development
      of Air Force medicine began with the U.S. education of Panagiotis Korombilis,
      founder of the Center for Flight Crew Health Examination in 1936. In 1976, the
      Air Force Medical Center was established in the General Air Force Hospital while
      the educational and medical work of Air Force physicians led to the development
      of Air Force Medicine and supported Olympic Airways and Military Air Force
      development, which provides aircraft and personnel for patient aeromedical
      evacuations. An organized aeromedical evacuation system based on the National
      Health System, however, began operating in 1982 and was upgraded in 1994.
      Currently, the flight surgeon's work remains important in supporting the Military
      Air Force by offering regular examinations at the Air Force Medical Center for
      all personnel flying on civil and military aircrafts, and by educating all the
      Greek territory and Cypriot Air Force surgeons (of the National Emergency
      Assistance Center and the Military Services) at the Air Force Medical Center.
      Their presence at Air Force bases is important, as is their support of the
      overall well-being of flight personnel, their assistance in upholding the
      territory's future by improving aircraft and equipment and by purchasing search
      rescue aeromedical evacuation helicopters and hospital aeromedical transportation
      aircraft capable of transporting seriously ill patients, their promotion of
      collaboration with other countries in educating Air Force surgeons, and in
      support of valuable human life according to the Hippocratic Oath.

PMID- 10954366
TI  - German acceleration research from the very beginning.
AB  - German airmen were experiencing G-induced physiological effects as early as WWI,
      although no research on acceleration physiology was conducted at that time in
      Germany. This changed in 1931 with the studies of Heinz von Diringshofen, who
      gained experience with prolonged acceleration in flight. The first German
      centrifuge was constructed by the von Diringshofen brothers and was in operation
      at the Air Ministry's Aeromedical Research Institute in Berlin from 1935-1945.
      After WWII, Otto Gauer and Heinz Haher authored the paper "Man under Gravity-Free
      Conditions," paving the way to manned space exploration and demonstrating the
      change of research interest from the effects of multiple G forces to those of
      zero G.

PMID- 10954367
TI  - Airlines emergency medical kits.

PMID- 10954368
TI  - Quantitative seismocardiography.

PMID- 10954369
TI  - Life Sciences Biomedical Engineering Branch Awards.

PMID- 10954370
TI  - Hubertus Strughold Award.

PMID- 10954371
TI  - Young Investigator Award.

PMID- 10954372
TI  - Society of NASA Flight Surgeons Lovelace Award.

PMID- 10954373
TI  - Race- and sex-specific ECG models for left ventricular mass in older populations.
      Factors influencing overestimation of left ventricular hypertrophy prevalence by
      ECG criteria in African-Americans.
AB  - The validity of the reported high prevalence of left ventricular hypertrophy
      (LVH) among African-American men and women has been questioned owing to
      conflicting echocardiographic evidence. We used echocardiographic left
      ventricular mass (LVM) from M-mode measurements to evaluate associations between
      LVM, body size, and electrocardiographic (ECG) variables in 3,627 white and
      African-American men and women 65 years of age and older who were participants of
      the Cardiovascular Health Study (CHS), a multicenter cohort study of risk factors
      for coronary heart disease and stroke. ECG amplitudes used in LVH criteria were
      substantially higher in African-Americans, with apparent LVH prevalence 2 to 3
      times higher in African American men and women than in white men and women,
      although there was no significant racial difference in echocardiographic LVM. The
      higher apparent LVH prevalence by Sokolow-Lyon criteria in African-American men
      is in part owing to smaller lateral chest diameter. In women, reasons for racial
      differences in ECG LVH prevalence remain largely unexplained although a small
      part of the excess LVH in African-American women by the Sokolow-Lyon criteria
      appears to be owing to a larger lateral chest semidiameter in white women. ECG
      variables alone were too inaccurate for LVM prediction, and it was necessary to
      incorporate in all ECG models body weight that was properly adjusted for race and
      sex. This resulted in modest LVM prediction accuracy, with R-square values
      ranging from .22 to .36. Race- and sex-specific ECG models introduced for LVM
      estimation with an appropriate adjustment for body size differences are expected
      to facilitate evaluation of LVH status in contrasting racial population groups.

PMID- 10954374
TI  - Heart rate variability of children with mitral valve prolapse.
AB  - Studies have indicated that adult patients with mitral valve prolapse (MVP) may
      have autonomic dysfunction. The purpose of this study was to evaluate heart rate
      variability (HRV) in children with MVP. Sixty-seven children with MVP (ages 6 to
      18 years; 30 boys and 37 girls) were consecutively studied and subdivided into
      those with or without symptoms. Thirty-seven normal age-matched children (17 boys
      and 20 girls) were studied as controls. The patients were further divided into 4
      age subgroups. HRV was measured using a 24-hour Holter electrocardiogram (ECG)
      system (Laser SXP Holter Analysis System, Marquette Electronics, Milwaukee, WI).
      The ECGs were analyzed in both time domain and frequency domain (spectral
      analysis). Symptomatic and asymptomatic children with MVP were combined for
      analysis because they were not significantly different in terms of their HRV. All
      time-domain indices, with the exception of SDANN (SD of the mean of RR intervals
      in all 5-minute segments of the 24-hour ECG), were significantly lower in
      children with MVP than in controls. Children with MVP showed significantly lower
      spectral power of the high frequency (HF) and low frequency (LF) components when
      compared with controls. The ratio of LF to HF (LF/HF) was significantly higher in
      children with MVP. Similar differences were observed in the 4 age subgroups. Sex
      differences in HRV were observed when girls had lower HRV compared with boys.
      Lower time-domain and frequency-domain indices of HRV in children with MVP are
      suggestive of decreased parasympathetic activity and a shift in sympathovagal
      balance. Various factors including differences in heart rate may contribute to
      sex differences in HRV.

PMID- 10954375
TI  - Normal limits of high-resolution signal-averaged ECG parameters of Japanese adult
      men and women.
AB  - High-resolution signal-averaged electrocardiography (Hi-Res ECG) has been found
      useful in measuring ventricular late potentials for identifying patients prone to
      life-threatening ventricular arrhythmias. Several studies have reported cut-off
      values (normal limits) of Hi-Res ECG parameters, including sex-specific limits,
      for adult population. However, there are no such studies reporting such limits in
      the Japanese population. Hi-Res ECGs were recorded from 482 normal healthy
      patients (204 men; 278 women) with no cardiac disease and normal
      electrocardiogram. Three Hi-Res ECG parameters filtered QRS duration (FQRSD), low
      amplitude signal duration under 40 microV of terminal QRS (LASD), and root mean
      square voltage in the terminal 40 milliseconds (RMSV) were analyzed. FQRSD was
      longer in men than in women (P < .0001). RMSV was larger in men than in women (P
      < .0001). There was no significant difference in LASD between men and women. The
      upper limit (90th percentile) of FQRSD was 116 milliseconds for women. The upper
      limit of LASD was 42 milliseconds for both men and women. The lower limit (10th
      percentile) of the RMSV was 14 microV for both men and women. There was no
      significant difference in the distributions of the Hi-Res ECG parameters between
      our study and an earlier study on mostly whites from the United States and
      Europe. The upper limits (90th percentile) of FQRSD and LASD in the Japanese
      normal patients were nearly the same as for whites. But, the lower limit (10th
      percentile) of RMSV in our Japanese normals was significantly smaller than that
      for whites. Therefore, it may be necessary to use race-specific normal limits for
      late potential analysis. Criteria for abnormal late potentials (defined as
      abnormal values in at least 2 of the 3 Hi-Res ECG parameters) were met in 18 of
      482 (3.7%) normal healthy patients. Further studies are needed to evaluate the
      role of these criteria in identifying cardiac patients with life-threatening
      arrhythmias in the Japanese population.

PMID- 10954377
TI  - A flexible method for simulating cardiac conduction in three-dimensional complex
      geometries.
AB  - In this article we present a method for creating a membrane-based computer model
      capable of representing a three-dimensional irregular domain. The spatial
      discretization of our model is based on the Finite Volume Method. In combination
      with a robust meshmaking tool, our method may be used to simulate conduction in
      an arbitrarily shaped, complex region. In this way, conduction in specific
      subregions of cardiac anatomy may be examined. The capabilities of this
      methodology are demonstrated through 3 examples. The first shows the influence of
      abrupt changes in tissue geometry on conduction parameters. The second highlights
      the ability of the model to incorporate interior boundaries and altered membrane
      properties. The final example shows the inclusion of a full description of the
      fiber architecture in a portion of the canine left ventricle. Future applications
      will make use of the model's capabilities to conduct investigations in complex
      regions including the atria.

PMID- 10954376
TI  - Spectral and bidirectional filters give different results for signal-averaged ECG
      analysis in patients with postmyocardial infarction. GISSI-3 Arrhythmias Substudy
      Investigators.
AB  - This study aims at assessing the specific effects of bidirectional filters (BF)
      and spectral filters (SF) on signal-averaged ECG (SAECG) analysis. The GISSI-3
      Arrhythmias Substudy collected SAECGs of 598 patients 10 +/- 4 days after
      myocardial infarction (MI) from 20 Italian coronary care units. BF and SF were
      applied on 340 and 258 patients, respectively. QRS duration (QRSD), low amplitude
      signal duration (LAS40), and root mean-square-voltage (RMS40) were measured with
      filters set at 40 to 250 Hz. For ventricular late potentials (VLP) detection
      filter-specific criteria were adopted: QRSD > 114 ms, LAS40 > 38 ms, RMS40 < 20
      microV for BF and QRSD > 120 ms, LAS40 > 38 ms, RMS40 < 20 microV for SF. VLP
      were considered present if any 2 of the criteria were met. The QRSD obtained by
      BF (100.6 +/- 13 ms) was shorter (P < .0001) than that obtained by SF (109.1 +/-
      12 ms). Nevertheless, a higher prevalence of VLP for patients with BF than for
      patients with SF was found (23.8% vs 16.7%; P < .04). Indeed, filter-specific
      criteria were able to avoid any differences in the prevalence of abnormal QRSD
      and LAS40, but not of RMS40 (25.6% vs 17.1%, P < .02). Finally, the difference of
      VLP prevalence was mainly owing to the higher number of abnormal pairs of RMS40 +
      LAS40 (58% vs 44%) for BF than for SF. This multicentric study suggests that
      after MI, BF and SF produce discordant results on low-amplitude signals of
      filtered QRS that are not avoided by adopting filter-specific criteria. On the
      contrary, specific criteria seem to be suitable for comparison of QRSD between
      different SAECG devices in post-MI patients.

PMID- 10954378
TI  - Atrial sensing performance of a single-lead VDD pacing system during physical
      activities.
AB  - This study was undertaken to evaluate the atrial sensing performance of a single
      lead atrial synchronous-ventricular pacing system during various physical
      activities on late follow-up. Fourteen patients (mean age 55 +/- 17 years) with a
      third-degree or high-degree atrioventricular block and normal sinus node function
      were treated with the single-lead Thera VDD (Medtronic, Inc, Minneapolis, MN)
      pacemaker system. Mean P-wave amplitude at implantation was 3.2 +/- 1.3 mV. To
      assess the VDD system performance, P-wave amplitudes during various physical
      maneuvers (supine, sitting, deep breathing, standing, and exercise; respectively)
      were measured and atrial sensing was evaluated at a mean follow-up of 11 +/- 4
      months. During deep breathing, minimum and maximum P-wave amplitudes (0.8 +/-
      0.7, 1.2 +/- 1.0 mV, respectively) were found to be significantly lower than the
      standing position (minimum, 1.1 +/- 0.9, maximum, 1.4 +/- 1.1 mV P = .02 in
      both). No significant difference was found during other physical maneuvers.
      During the testing maneuvers, atrial undersensing was observed in 8 patients
      (57%) at the nominal atrial sensitivity of 0.5 mV. After increasing the atrial
      sensitivity (0.25 mV), no sensing failure was observed in these patients. It has
      been concluded that Medtronic Thera VDD system is a safe and reliable device with
      an easy implantation technique providing effective atrioventricular
      synchronization. The sensing problems, which may occur on late follow-up, can be
      corrected successfully by reprogramming. To achieve an optimal atrial sensing
      function in patients with a single-lead VDD pacing, we recommend that the atrial
      sensing capability should be examined in various physical maneuvers.

PMID- 10954379
TI  - Lack of an association between T-wave alternans and ST-segment depression during
      exercise-induced ambulatory ischemia.
AB  - It is known that T-wave alternans (TWA), which identify patients at risk for
      arrhythmic events, often occur during acute coronary occlusion in association
      with ST-segment elevation. To test the hypothesis that TWA is associated with a
      certain state/severity of myocardial infarction/ischemia, we assessed the
      association between TWA and ST-segment depression during exercise-induced
      ambulatory ischemia. Of 351 consecutive patients with coronary artery disease who
      underwent assessment of microvolt TWA by exercise, 23 patients with effort angina
      without a history of infarction with ST depression (> or =0.11 mV) during TWA
      test were selected. These patients were compared with 222 postinfarction patients
      consisting of 38 patients with, and 184 patients, without the ST depression, and
      18 normal individuals. The incidence (9%) of determinate TWA in the patients with
      angina was significantly (P < .0001) lower than that (52%) in the postinfarction
      patients. There was no significant difference between the angina patients and the
      controls (6%). There was also no difference between the patients with (58%) and
      without the ST depression (51%) in the postinfarction patients. Moreover, no
      correlation existed between the TWA voltage and the ST-depression magnitude in
      both angina and postinfarction patients. We concluded that there is no
      association between TWA and ambulatory ischemia with ST depression.

PMID- 10954381
TI  - Hemodynamic collapse, geometry, and the rapidly paced upper limit of ventricular
      vulnerability to fibrillation by T-wave stimulation.
AB  - There is an upper limit to the vulnerability (ULV) of the ventricles to
      fibrillation (VF) induced by T-wave stimuli. Across species, disease states, and
      pharmacological treatments, the ULV is correlated to the defibrillation threshold
      (DF50). However, one factor known to increase the ULV far above the DF50 is rapid
      pacing. In this article we test the hypothesis that this increase is owing to an
      accompanying hemodynamic collapse or geometric change. In 18 dogs, T-wave stimuli
      were delivered from transvenous defibrillating electrodes. The T-wave shock
      strength that induced VF 50% of the time (the ULV50) was measured using a 10-step
      Bayesian up-down protocol. T-wave stimuli were delivered after 15 paced beats at
      one of several rates: normal (80% of the R-R interval), rapid (the interval just
      fast enough to cause hemodynamic collapse), or 10 milliseconds greater than rapid
      (which did not cause hypotension). We measured the geometry of the left ventricle
      at the moment of T-wave stimulation using linear ultrasound. Rapid pacing
      significantly increased the ULV50 above the normal rate ULV (507 +/- 62.9 vs 379
      +/- 70.6 V, P < .005, n = 18), even in the subset without hemodynamic collapse
      (505 +/- 84.4 vs 394 +/- 66.5 V, P < .005, n = 6). No significant geometric
      changes were noted between rapid (19.8 mm) and normal (20.6 mm, n = 6, P < NS)
      pacing, but QT interval reduction appears to correlate with the ULV50 (QT vs
      ULV50, r > 0, P < .01). Rapid pacing can dramatically increase the measured
      ULV50. The most likely cause is a concurrent change in the electrophysiology, eg,
      QT or APD, of the myocardium. As the only known factor to consistently alter the
      relationship between ULV and the DF50, rapid pacing offers a unique opportunity
      for the study of the link between defibrillation and ULV testing.

PMID- 10954380
TI  - Nicorandil attenuates both temporal and spatial repolarization alternans.
AB  - T-wave alternans (TWA) on the electrocardiogram have been frequently associated
      with long QT syndrome (LQTS) and abrupt rate change. The present study
      investigated the effect of the potassium channel opener nicorandil on the
      repolarization alternans at the endocardium and the epicardium in the left
      ventricle. Electrocardiogram and transmural monophasic action potentials from the
      endocardium and the epicardium were simultaneously recorded in Langendorff
      perfused guinea pig hearts. The hearts were paced at a basic cycle length (BCL)
      of 240 ms and the cycle length (CL) was abruptly shortened to 170 ms to induce
      repolarization alternans. Disopyramide and nicorandil were used to increase or
      attenuate repolarization alternans, respectively. Repolarization alternans were
      numerically expressed as the sum of the absolute difference between consecutive
      monophasic action potential durations at 90% repolarization (MAPD90) in the first
      10 beats. In the control hearts, the MAPD90 alternans were 78.6 +/- 14.9 ms at
      the endocardium, and 49.8 +/- 58 ms at the epicardium (P = .03 endocardium vs
      epicardium). Disopyramide (2 microg/mL) increased the MAPD90 alternans to 186.6
      +/- 30.6 ms at the endocardium and 116.4 +/- 16.5 ms at the epicardium, and
      enhanced the difference of repolarization alternans between the endocardium and
      the epicardium (transmural dispersion) from 28.8 +/- 11.3 ms to 70.2 +/- 18.7 ms
      (P = .02 vs controls). Nicorandil (400 ng/mL) suppressed the MAPD90 alternans to
      79.6 +/- 16.3 ms at the endocardium and 56.0 +/- 11.8 ms at the epicardium, and
      attenuated the transmural dispersion to 23.6 +/- 6.0 ms (P = .02 vs disopyramide
      administrated hearts). Our results suggest that nicorandil attenuates both
      temporal (beat-to-beat) and spatial (between the endocardium and the epicardium)
      repolarization alternans induced by the combination of cycle length changes and
      disopyramide administration.

PMID- 10954382
TI  - The power of PACs.
AB  - An elderly woman was admitted for palpitation, light-headedness, and syncope.
      Telemetry strips revealed numerous episodes of supraventricular tachycardia (SVT)
      as well as premature beats and pauses. Analysis of the effects of spontaneous
      premature atrial contractions (PACs) on both the sinus discharge rate and on the
      SVTs revealed strict relationships that helped decipher the electrophysiological
      mechanisms of the arrhythmias and offered a rational approach to treatment.
      Invasive electrophysiological evaluation was not needed. A hitherto unreported
      phenomenon was the predictable termination of reentrant SVTs by spontaneous PACs.
      This instructional exercise shows the power of PACs in triggering and terminating
      arrhythmias, as well as their ability to serve as diagnostic tools in arrhythmia
      analysis.

PMID- 10954383
TI  - Bupivacaine-induced myocardial depression and pulmonary edema: a case report.
AB  - Central nervous system and cardiovascular toxicity are well-known side effects of
      bupivacaine. We report a case of bupivacaine-induced myocardial depression and
      cardiogenic pulmonary edema. A previously healthy woman developed soon after
      bupivacaine epidural injection of 5 mL 0.5% (25 mg) cardiogenic shock complicated
      with pulmonary edema. There were pronounced rales on auscultation with a
      butterfly sign on chest radiograph. A cardiac ultrasound showed reduced
      myocardial contractility, diffuse hypokinesia, left ventricular ejection fraction
      (LVEF) 25%, mitral and pulmonary insufficiency. Right heart catheterization
      showed increased pulmonary artery wedge pressure (34 mm Hg) and a pulmonary
      artery pressure of 48 over 33 mm Hg. These findings suggest myocardial depression
      owing to bupivacaine sodium channel blocking of myocardial nerve and tissue and
      subsequent reduction of myocardial contractility. The patient completely
      recovered with normalization of clinical, roentenographic, ultrasound, and
      hemodynamic findings and discharged 10 days later in good condition.

PMID- 10954384
TI  - Conduction issues.

PMID- 10954385
TI  - The future of Australasian psychiatrists: online or out of touch?
AB  - OBJECTIVE: The aim of this paper is to examine the delivery of mental health care
      which will be enabled by the various communications technologies over the next 5
      to 10 years. METHOD: A literature review, reviews of multiple Internet websites
      and the author's personal experience and opinions are combined to provide a
      commentary on the group of new technologies for communication available within
      health, and how they will affect the practice of psychiatry and psychiatrists
      over the next decade. The driving forces for these changes are the rise of
      consumerism, technological change and financial necessity, and it is evident that
      patients will have in future much greater choice of access to their therapists
      than at present. The health-care environment of the future will be different to
      today, as will the roles of psychiatrists, who will increasingly have to work as
      members of teams in an expert capacity rather than in traditional one-to-one
      practice. CONCLUSIONS: It is concluded that it is essential for psychiatrists to
      become involved in online health care, and in particular to join their patients
      on the Internet, and that there are major opportunities for Australasian
      psychiatrists to provide high quality psychiatric care across national
      boundaries, particularly into the Asia-Pacific region.

PMID- 10954386
TI  - Signal transmission, rather than reception, is the underlying neurochemical
      abnormality in schizophrenia.
AB  - OBJECTIVE: This review aims to summarise the outcome of studies on changes in the
      molecular architecture of the brain of subjects with schizophrenia and formulate
      a hypothesis on mechanisms involved in the pathology of the illness. METHOD: The
      outcomes from key studies using neuroimaging techniques and tissue obtained post
      mortem that have been directed toward identifying abnormalities in the molecular
      architecture of the brain in subjects with schizophrenia were summarised. Using
      the results from these studies hypotheses were formulated on the underlying
      pathological process that precipitate schizophrenia. RESULTS: Studies using
      neuroimaging techniques or tissue obtained post-mortem have revealed changes in
      the dopaminergic, serotoninergic, glutamatergic, GABAergic and cholinergic
      systems of the brain in schizophrenia. Some of these studies have identified
      abnormalities in presynaptic proteins or functioning that may be central to the
      pathology of schizophrenia. CONCLUSIONS: There appears to be diverse changes in
      the molecular cytoarchitecture of the brains from subjects with schizophrenia. It
      could be that it is by affecting these multiple systems that the atypical
      antipsychotic drugs produce their improved clinical outcomes. Abnormal
      functioning of presynaptic processes could be central to the pathology of
      schizophrenia. If the 'presynaptic' hypothesis is proven, future antipsychotic
      drug design should be directed away from post-synaptic receptor antagonism toward
      the modulating the functions of presynaptic neurones.

PMID- 10954387
TI  - Mental health disorders in children and young people: scope, cause and
      prevention.
AB  - OBJECTIVE: To review the scope and characteristics of mental health disorders in
      children and young people in Australia; detail some emerging concepts of the
      causal pathways of mental health disorders in children and young people; and
      discuss aspects of the prevention of mental health disorders and the promotion of
      mental health in children and young people. METHOD: An integrated review of
      selected literature. RESULTS: (i) While as many as one in five Australian
      children aged from four to 17 have significant mental health problems there
      remains a need for prevalence estimates in subsections of the population, notably
      children and young people of Aboriginal and Torres Strait Islander descent; (ii)
      appropriate studies of gene-environment interaction will require better
      measurement and developmental exposition of those risk exposures that are known
      to be on the causal pathway to mental health disorder; and (iii) universal,
      selective and indicated prevention trials and evaluations directed at anxiety,
      depression and conduct disorder are needed. CONCLUSION: Preventive intervention
      and promotion in mental health must entail effective collaboration at national,
      state and local levels between health, welfare and education sectors. These
      sectors must be informed by high quality epidemiology and a knowledge of the
      causal pathways of mental health disorders. Such intervention must also improve
      the movement of scientific knowledge to political policy on one hand and to
      praxis on the other. This will require a clear and persistent vision of the
      urgency, costs and consequences of mental health disorders in children and young
      people coupled with effective leadership and political resolve.

PMID- 10954388
TI  - Youth mental health promotion in the Hunter region.
AB  - OBJECTIVE: To describe the work of the Hunter Institute of Mental Health, with
      special emphasis on its role in mental health promotion and prevention with
      adolescents. METHOD AND RESULTS: The Ottawa Charter for Health Promotion is used
      as a framework to describe the varied functions of this organisation. Four youth
      mental health promotion programs are given as examples of the Institute's work.
      Results of preliminary evaluation of the Youth Suicide Prevention - National
      University Curriculum Project are provided. CONCLUSION: The Hunter Institute of
      Mental Health, a self-funding unit of the Hunter Area Health Service, provides
      innovative health promotion programs as part of its role as a provider of mental
      health education and training. The model may be particularly applicable to mental
      health services in regional Australia.

PMID- 10954390
TI  - MindMatters, a whole-school approach promoting mental health and wellbeing.
AB  - OBJECTIVE: MindMatters is an innovative, national mental health promotion program
      which provides a framework for mental health promotion in Australian schools. Its
      objectives are to facilitate exemplary practice in the promotion of whole-school
      approaches to mental health promotion; develop mental health education resources,
      curriculum and professional development programs which are appropriate to a wide
      range of schools, students and learning areas; trial guidelines on mental health
      and suicide prevention and to encourage the development of partnerships between
      schools, parents, and community support agencies to promote the mental wellbeing
      of young people. METHOD: A team of academics and health education professionals,
      supported by a reference group of mental health experts, developed MindMatters.
      The program was piloted in 24 secondary schools, drawn from all educational
      systems and each State and Territory in Australia. The pilot program was amended
      and prepared for dissemination nationally. RESULTS: The program provides a
      framework for mental health promotion in widely differing school settings. The
      teacher professional development dimension of the program is central to enhancing
      the role of schools in broad population mental health promotion. CONCLUSIONS:
      Promoting the mental health and wellbeing of all young people is a vital part of
      the core business of teachers by creating a supportive school environment that is
      conducive to learning. Teachers need to be comfortable and confident in promoting
      and teaching for mental health. Specific, targeted interventions, provided within
      a whole-school framework, address the needs of the minority of students who
      require additional support.

PMID- 10954389
TI  - The Gatehouse Project: a systematic approach to mental health promotion in
      secondary schools.
AB  - OBJECTIVE: The objective of this paper is to outline the conceptual background
      and strategy of intervention for a systematic and sustainable approach to mental
      health promotion in secondary schools. METHOD: The conceptual origins of the
      Gatehouse Project are described in terms of the epidemiology of adolescent mental
      health problems, attachment theory, education reform research and health
      promotional theory and practice. The elements of health promotional work are
      described in terms of structural change and priority setting; implementation at
      multiple levels within the participating schools is described. RESULTS: The
      conceptual framework of the Gatehouse Project emphasises healthy attachments with
      peers and teachers through the promotion of a sense of security and trust,
      effective communication and a sense of positive self-regard based on
      participation in varied aspects of school and community life. A school social
      climate profile is derived from a questionnaire survey of students. An adolescent
      health team uses this information to set priorities for change within the school.
      Interventions may focus on the promotion of a positive social climate of the
      whole school or in the classroom. Curriculum-based health education is also used
      and based on materials that are relevant to the normal developmental experiences
      of teenagers. These are integrated into the mainstream curriculum and incorporate
      a strong component of teacher professional development. Lastly, the intervention
      promotes linkage between the school and broader community with a particular
      emphasis on the needs of young people at high risk of school drop-out.
      CONCLUSIONS: Educational environments are complex systems undergoing continuous
      and simultaneous changes. The Gatehouse Project will provide unique information
      on the relationship between the social environment and the emotional wellbeing of
      young people. More importantly it outlines a sustainable process for building the
      capacity of schools to promote the social and emotional development of young
      people.

PMID- 10954391
TI  - Mental health nurses' beliefs about interventions for schizophrenia and
      depression: a comparison with psychiatrists and the public.
AB  - OBJECTIVE: The main objective of this paper was to investigate and compare mental
      health nurses' beliefs about interventions for schizophrenia and depression with
      those of psychiatrists and the public. Factors affecting nurses' beliefs were
      also investigated. METHOD: This research used methods employed in previous
      surveys of professional and public beliefs. A postal survey of 673 Australian
      mental health nurses was carried out. The survey was comprised of a vignette
      describing a person with either depression or schizophrenia. Participants rated
      whether particular medical, psychological and lifestyle interventions were
      helpful, harmful or neither. Factors examined included: nurses' age, sex, degree
      of contact with similar problems, work setting, level of highest qualification
      and whether their education was hospital-based or completed within the tertiary
      sector. RESULTS: The nurses agreed with psychiatrists (but not the public) about
      the interventions most likely to be helpful, such as antidepressants for
      depression and antipsychotic medication for schizophrenia. However, there were
      many differences between nurses, psychiatrists and the public. Nurses were more
      likely than psychiatrists to believe that certain non-standard interventions such
      as vitamins, minerals and visiting a naturopath would be helpful. Nurses' beliefs
      tended to form a bridge between the attitudes of psychiatrists and the public for
      some of these non-standard interventions. Age, work setting and qualifications
      were related to nurses' intervention beliefs. CONCLUSIONS: Mental health
      practitioners need to be aware of a range of beliefs within mental health
      services. The acknowledgement of differing belief systems is important for high
      quality, integrated care.

PMID- 10954392
TI  - Attitudes towards people with depression: effects on the public's help-seeking
      and outcome when experiencing common psychiatric symptoms.
AB  - OBJECTIVE: To determine whether people's attitudes towards a person who has
      experienced depression influence them in (i) the types of actions they take to
      help themselves if they experience common psychiatric symptoms, and (ii) the
      degree to which their symptoms improve. METHOD: A postal survey was carried out
      with 3,109 adults to assess attitudes and symptoms of anxiety and depression.
      Attitudes were assessed by questions on a depressed person's likely long-term
      outcome in various areas of life and whether the respondents thought the
      depressed person was likely to experience discrimination. A follow-up survey was
      carried out 6 months later with 422 persons who had a high level of symptoms at
      baseline. These individuals were asked about whether they had taken various
      actions to relieve their symptoms. RESULTS: The attitude measures did not predict
      use of actions which involved someone else having to know that the person had
      psychiatric symptoms, nor use of actions which did not. The attitude measures
      also did not predict change in anxiety and depression symptoms. CONCLUSIONS: The
      attitude measures did not predict patterns of help-seeking or outcome for people
      with common psychiatric symptoms. However, attitudes towards depression were
      quite benign and the situation could be different for people with severe mental
      disorders.

PMID- 10954393
TI  - Public beliefs about the helpfulness of interventions for depression: effects on
      actions taken when experiencing anxiety and depression symptoms.
AB  - OBJECTIVE: Previous research has shown that the public have different beliefs to
      mental health professionals about the helpfulness of interventions for mental
      disorders. However, it is not known whether the public's beliefs actually
      influence their behaviour when they develop psychiatric symptoms. METHOD: A
      postal survey of 3,109 Australian adults was used to assess beliefs about the
      helpfulness of a broad range of interventions for depression, as well as
      respondents' current level of anxiety and depression symptoms and any history of
      treated depression. A follow-up survey of 422 persons who had a high level of
      symptoms at baseline was conducted 6 months later. These people were asked which
      interventions they had used to reduce their symptoms. An analysis was carried out
      to see whether beliefs and other factors at baseline predicted subsequent use of
      interventions. RESULTS: There were some major discrepancies between the ranking
      of interventions as likely to be helpful and the ranking of how frequently they
      were actually used. Interventions involving mental health professionals were
      often rated as likely to be helpful, but were rarely used in practice. Other
      simple, cheap and readily available interventions were used the most frequently,
      but were not the most likely to be rated as helpful. The most consistent
      predictors across all interventions used were gender, history of treatment,
      current symptoms and belief in a particular intervention. Of particular interest
      was the finding that beliefs in the helpfulness of antidepressants predicted
      their use. However, beliefs were not predictors of use for all interventions.
      CONCLUSIONS: Beliefs about the helpfulness of an intervention did not always
      predict actual use of that intervention, although beliefs did predict use of
      antidepressants. Therefore, campaigns that change public beliefs about effective
      treatments may also influence actual use of treatments. Interventions preferred
      by professionals are not frequently used at present. Most people with anxiety and
      depression symptoms rely primarily on simple self-help interventions, the
      effectiveness of which has been little researched.

PMID- 10954394
TI  - A comparative mental health literacy survey of psychiatrists and other mental
      health professionals in Singapore.
AB  - OBJECTIVE: The objectives of this study are, first, to replicate and extend an
      Australian approach to assessing mental health literacy by studying a sample of
      Singapore mental health professionals, and to focus on differences between
      judgements made by the psychiatrists in comparison with the other mental health
      professionals. Second, to compare the psychiatrists' judgements with those of
      Australian psychiatrists. METHOD: The Australian questionnaire, assessing
      responses in relation to vignettes of major depression and to schizophrenia was
      extended by adding a third vignette of mania, and by the addition of several
      region-specific response options. Nearly 500 questionnaires were distributed to
      representative staff (psychiatrists, nurses and allied health) of a large
      psychiatric institution in Singapore, with a response rate of 81%. Psychiatrists'
      judgements were compared with all other hospital staff, and with Australian
      psychiatrists' judgements. RESULTS: The two principal contrast groups (Singapore
      psychiatrists and other Singapore mental health professionals) differed slightly
      in terms of diagnostic accuracy. The psychiatrists differed in favouring a more
      professionally focused model of intervention, while both professional groups
      viewed traditional healers and their practices as distinctly unhelpful. Direct
      comparison of psychiatrist ratings generated in Singapore and in Australia
      revealed quite similar response profiles. CONCLUSIONS: In addition to generating
      data of some intrinsic importance, comparison with Australian survey data allows
      the potential impact of regional and cultural differences, as well as of varying
      psychiatric practices, to be identified. Responses identified more similarities
      than differences in the judgements of the psychiatrists from the two countries.

PMID- 10954395
TI  - Defining effective community support for long-term psychiatric patients according
      to behavioural principles.
AB  - OBJECTIVE: The purpose of this article is to define the characteristics of
      effective support in community mental health settings for patients with serious
      and persistent mental illness. METHOD: A broad literature providing empirical
      evidence on competent caregiver behaviours and styles is selectively reviewed.
      Relevant findings from family caregiver research and studies of social
      environments that enhance skill development in people with intellectual
      disabilities are incorporated, within a cognitive-behavioural framework. RESULTS:
      Six important domains are identified which represent positive caregiver styles:
      acceptance, creating a positive atmosphere, expectations of change,
      responsiveness, normalisation and educativeness. CONCLUSION: The characteristics
      hypothesised to be critical for caregivers and support workers are defined in a
      general way that can allow for individualisation according to the goals of the
      programs and the cultural priorities of staff and patients. Further empirical
      validation of these characteristics would enable community mental health services
      to provide more specialised clinical treatments.

PMID- 10954396
TI  - How high a dose of stimulant medication in adult attention deficit hyperactivity
      disorder?
AB  - OBJECTIVE: This paper examines clinical and neuroscientific evidence to address
      the question whether high doses of stimulant drugs offer additional advantages in
      the treatment of adult attention deficit hyperactivity disorder (ADHD) and at
      what cost. It attempts to arrive at a reasonable upper limit of dosage for
      clinical purposes. METHOD: The study involves a selective review of the treatment
      studies of ADHD in children and adults and an examination of the pharmacokinetic
      and pharmacodynamic data on psychostimulants in humans and animals. RESULTS AND
      CONCLUSIONS: The clinical and experimental data justify the use of chronic low
      dose stimulant treatment of ADHD in adults, with the recommended upper limit of
      dose being 1 mg/kg for methylphenidate and 0.5 mg/kg for dexamphetamine. There is
      no empirical evidence of greater improvement with higher doses and any beneficial
      effect is likely to be compromised by the adverse effects, some of which can be
      very serious. The recommended doses should be exceeded only after careful
      consideration and objective documentation of beneficial and adverse consequences.
      Monitoring of drug levels in blood may be of some value for compliance or
      pharmacokinetic considerations, as there is a direct relationship between blood
      and brain levels as well as dopamine transporter occupancy. These recommendations
      are tentative and further clinical research is warranted.

PMID- 10954397
TI  - Comparative efficiency ratings between public and private acute inpatient
      facilities.
AB  - OBJECTIVES: The aims of this study are to compare clinical outcomes and
      efficiency ratings in an acute psychiatric inpatient facility with findings from
      other studies, and to examine relationships between symptom severity, admission
      medico-legal status and length of stay. METHOD: The Health of the Nation Outcome
      Scales was administered at admission and discharge and analysed against admission
      medico-legal status and length of stay. Efficiency ratings were calculated and
      compared with those from other acute psychiatric inpatient settings. RESULTS:
      Clinical outcomes and efficiency ratings were similar to those from other public
      acute inpatient facilities, with greater admission severities and higher
      efficiency ratings than those found in private facilities. Involuntary
      hospitalisation was found to be associated with higher admission severities and
      longer lengths of stay. CONCLUSIONS: Outcome or effect size is enhanced by higher
      admission severities, however, mean outcome per 10 days of stay is decreased by
      involuntary admission legal status. Factors unrelated to admission legal status
      effect differences in efficiency ratings found between public and private acute
      psychiatric inpatient facilities.

PMID- 10954398
TI  - The measurement of a case manager's workload burden.
AB  - OBJECTIVE: The aim of this activity was to develop an appropriate scale to
      accurately assess the level of clinical load carried by each case manager at the
      Royal Brisbane Hospital Integrated Mental Health Service. METHOD: A survey of,
      and consultation with, case managers over a period of 15 months was used to
      gather data and modify the monitoring tool for future use in the service. RESULTS
      AND CONCLUSION: Analysis of the data gathered revealed the level of case
      managers' work load burden and the depth of need required by clients.
      Professionally the Clinical Load Monitoring scores have been used in the
      allocation of additional cases for case management and in the supervision by
      discipline seniors. Service management has used the Clinical Load Monitoring
      Scale by dividing individual caseloads into low, medium and heavy service users -
      with low service users being further investigated for discharge from the service.
      Heavy service users were assessed for entry into more intensive treatment areas.

PMID- 10954399
TI  - Health insurance status and mood during pregnancy and following birth: a
      longitudinal study of multiparous women.
AB  - OBJECTIVE: The objective of this study was to investigate the relationship
      between health insurance status and mood during pregnancy and following
      childbirth. METHOD: 320 women were recruited in the early stage of pregnancy to
      participate in a longitudinal, prospective study of the psychological aspects of
      childbirth among multiparous women. Study volunteers were surveyed during each
      trimester of pregnancy and 2 and 8 months following childbirth. A range of self
      administered psychometric tests were used to assess mood (Profile of Mood State),
      locus of control, defence style and partner support. Demographic information
      including health insurance status was noted at study entry. RESULTS: Public
      patients consistently had a more disturbed mood compared with private patients.
      This difference reached statistical significance during the second and third
      trimesters of pregnancy and 8 months after birth. Multivariate analysis was
      undertaken to identify predictors of mood during pregnancy and following birth. A
      better mood score was positively associated with private health insurance, a more
      caring partner and mature defence style, and negatively associated with external
      locus of control and immature defence style. A distinct mood pattern during
      pregnancy and following childbirth was observed and is described. CONCLUSIONS:
      Public patients have a more disturbed mood during pregnancy and following
      childbirth compared with private patients. This information is relevant when
      planning social, psychological and psychiatric services that target childbearing
      women.

PMID- 10954401
TI  - Trends in Maori mental health in Otago.
AB  - OBJECTIVE: This paper outlines the methods used, and preliminary descriptive data
      collected, in a study on a cohort of Maori and non-Maori patients admitted to the
      inpatient psychiatric services in Otago between 1990 and 1992. METHOD: The notes
      of 42 Maori and 217 non-Maori first admissions to psychiatric inpatients were
      reviewed. Information concerning this admission was entered onto a database and
      analysed. RESULTS: The Maori admission rate was 4 per 1000 compared with 1 per
      1000 for non-Maori people. This was higher than expected based on Otago
      population figures. Rates of family psychiatric history did not differ between
      Maori and non-Maori. Although Maori were found to have higher rates of social
      welfare support and were more likely to have no academic qualifications the
      differences were not significant. The sources of referral for Maori admissions
      were more likely to be from the law, and Maori were more likely to have had prior
      psychiatric inpatient treatment. The most common diagnosis for Maori and non
      Maori was depressive disorders, and suicidal behaviour was common. CONCLUSIONS:
      Maori are overrepresented among first psychiatric inpatient admissions in Otago.
      They appear to be a more disadvantaged group with respect to financial support,
      academic qualifications and other health problems. The most common diagnosis did
      not differ between Maori and non-Maori cohorts.

PMID- 10954400
TI  - What is the role of procedural justice in civil commitment?
AB  - OBJECTIVE: To determine best practice management strategies in the clinical
      application of civil commitment. METHOD: All relevant literature on the topics of
      'civil commitment', 'coercion' and 'procedural justice' were located on MEDLINE
      and PsychLIT databases and reviewed. Literature on the use of Ulysses contracts
      and advance directives in mental health treatment was integrated into the
      findings. RESULTS: Best practice evidence that guides management strategies is
      limited to the time of enactment of civil commitment. Management strategies
      involve enhancing the principles of procedural justice as a means of limiting
      negative patient perception of commitment. In the absence of evidence-based
      research beyond this point of enactment, grounds for the application of the
      principles of procedural justice are supported by reference to ethical
      considerations. Ulysses contracts provide an additional method for strengthening
      procedural justice. CONCLUSIONS: Procedural justice principles should be
      routinely applied throughout the processes of civil commitment in order to
      enhance longer term therapeutic outcomes and to blunt paternalism.

PMID- 10954402
TI  - Diurnal variation in Cotard's syndrome (copresent with Capgras delusion)
      following traumatic brain injury.
AB  - OBJECTIVE: The aim of this paper is to document regular nocturnal intensification
      of delusional nihilistic and persecutory ideas (Cotard delusion) linked with
      extreme depersonalisation and hypervivid dreaming. CLINICAL PICTURE: A 17-year
      old man presented with Cotard and Capgras delusions after sustaining multiple
      cognitive impairments secondary to traumatic brain injury. TREATMENT AND OUTCOME:
      Delusional ideation fully resolved within 14 days of commencement of olanzapine 5
      mg daily. CONCLUSION: This patient's experience of perceptual abnormalities and
      impairments in meta-abilities related to self-monitoring and critical inferencing
      lends support to multicomponent sensory processing accounts of brain injury
      related, content-specific delusional syndromes.

PMID- 10954403
TI  - Cognitive-behavioural assessment and treatment of maladaptive help-seeking
      behaviour in a patient with schizophrenia.
AB  - OBJECTIVE: Maladaptive help-seeking behaviour in psychiatric patients is a
      significant problem for public mental health services, yet it is not addressed in
      the mainstream literature. We present a report on the successful treatment of a
      person with schizophrenia who displayed this common dilemma for patients and
      clinicians. CLINICAL PICTURE: A 31-year-old man with borderline intellectual
      functioning had a 10-year history of schizophrenia marked by negative features.
      He frequently presented in crisis to public mental health services, the local
      hospital, and his general practitioner; this resulted in excessive use of
      services, including admissions. TREATMENT: The patient was reassessed from a
      cognitive-behavioural perspective rather than a syndromal perspective. Specific
      behaviours were modified, cognitions were identified, challenged and
      restructured, and other service providers were provided with an alternative to
      admission or acute community care. OUTCOME: At 24 months the maladaptive
      behaviour remains in remission. CONCLUSIONS: Behavioural problems in persons with
      chronic schizophrenia may be effectively treated by reconceptualising the
      behaviour as distinct from the major diagnosis.

PMID- 10954404
TI  - Response to: 'Prolonged fatigue, anxiety and depression: exploring relationships
      in a primary care sample'.

PMID- 10954405
TI  - Uncertain efficacy for psychotherapy for borderline patients: a methodologist's
      lament.

PMID- 10954407
TI  - A case of interstitial nephritis on clozapine.

PMID- 10954406
TI  - Social skills training for a case of Savant syndrome and Asperger's syndrome.

PMID- 10954409
TI  - Recurrent neuroleptic malignant syndrome.

PMID- 10954408
TI  - What's in a name?

PMID- 10954410
TI  - Cannabis and psychosis.

PMID- 10954411
TI  - Neuroleptic rechallenge following neuroleptic malignant syndrome.

PMID- 10954412
TI  - Plakoglobin and beta-catenin: protein interactions, regulation and biological
      roles.
AB  - Beta-catenin can play different roles in the cell, including one as a structural
      protein at cell-cell adherens junctions and another as a transcriptional
      activator mediating Wnt signal transduction. Plakoglobin (gamma)-catenin), a
      close homolog of beta-catenin, shares with beta-catenin common protein partners
      and can fulfill some of the same functions. The complexing of catenins with
      various protein partners is regulated by phosphorylation and by intramolecular
      interactions. The competition between different catenin partners for binding to
      catenins mediates the cross-talk between cadherin-based adhesion, catenin
      dependent transcription and Wnt signaling. Although plakoglobin differs from beta
      catenin in its functions and is unable to compensate for defects in Wnt signaling
      resulting from lack of beta-catenin, recent evidence suggests that plakoglobin
      plays a unique role in Wnt signaling that is different from that of beta-catenin.
      The functional difference between catenins is reflected in their differential
      involvement in embryonic development and cancer progression.

PMID- 10954413
TI  - Eukaryotic signal transduction via histidine-aspartate phosphorelay.
AB  - Transmembrane signal transduction is a feature common to all eukaryotic and
      prokaryotic cells. We now understand that a subset of the signalling mechanisms
      used by eukaryotes and prokaryotes are not just similar in principle, but
      actually use homologous proteins. These are the histidine-aspartate
      phosphorelays, signalling systems of eubacterial origin, now known to be
      widespread in eukaryotes outside the animal kingdom. Genome projects are
      revealing that His-Asp phosphorelays are present as multigene families in lower
      eukaryotes and in plants. A major challenge is to understand how these 'novel'
      signal transduction systems form integrated networks with the more familiar
      signalling mechanisms also present in eukaryotic cells. Already, phosphorelays
      have been characterised that regulate MAP kinase cascades and the cAMP/PKA
      pathway. The probable absence of His-Asp phosphorelays from animals has generated
      interest in their potential as targets for anti-microbial therapy, including
      antifungals. Recent findings suggest that this approach holds promise.

PMID- 10954414
TI  - Lumenal targeted GFP, used as a marker of soluble cargo, visualises rapid ERGIC
      to Golgi traffic by a tubulo-vesicular network.
AB  - The mechanism by which soluble proteins without sorting motifs are transported to
      the cell surface is not clear. Here we show that soluble green fluorescent
      protein (GFP) targeted to the lumen of the endoplasmic reticulum but lacking any
      known retrieval, retention or targeting motifs, was accumulated in the lumen of
      the ERGIC if cells were kept at reduced temperature. Upon activation of
      anterograde transport by rewarming of cells, lumenal GFP stained a microtubule
      dependent, pre-Golgi tubulo-vesicular network that served as transport structure
      between peripheral ERGIC-elements and the perinuclear Golgi complex. Individual
      examples of these tubular elements up to 20 microm in length were observed. Time
      lapse imaging indicated rapid anterograde flow of soluble lumenal GFP through
      this network. Transport tubules, stained by lumenal GFP, segregated rapidly from
      COPI-positive membranes after transport activation. A transmembrane cargo marker,
      the temperature sensitive glycoprotein of the vesicular stomatitis virus, ts-045
      G, is also not present in tubules which contained the soluble cargo marker lum
      GFP. These results suggest a role for pre-Golgi vesicular tubular membranes in
      long distance anterograde transport of soluble cargo. http://www.
      biologists.com/JCS/movies/jcs1334.html

PMID- 10954415
TI  - Transient suppression of cortactin ectopically induces large telencephalic
      neurons towards a GABAergic phenotype.
AB  - Excitatory and inhibitory neuronal cell fates require specific expression of both
      neurotransmitter and morphological phenotypes. The role of the F-actin
      cytoskeleton in morphological phenotypes has been well documented, but its role
      in neurotransmitter phenotype expression remains unknown. Here we present
      evidence that the F-actin binding protein cortactin participates in determining
      both aspects of cell fate in large telencephalic neurons. We show that the
      expression of cortactin was upregulated early in development just prior to
      appearance of GABAergic neurons in the chick telencephalon at embryonic day 6.
      This program was faithfully maintained in primary neuronal cultures derived from
      E6 telencephalon, where immature neurons differentiate either to large pyramidal
      and large stellate excitatory neurons or to small inhibitory GABAergic neurons.
      Immunostaining revealed that cortactin was enriched in areas of membrane budding,
      growth cones, and in the cell cortex of immature neurons. With differentiation,
      intense punctate staining was also observed in an extraction-resistant cytosolic
      compartment of the soma and processes. More importantly, suppression of cortactin
      by inhibition of cortactin mRNA translation with antisense oligonucleotides
      caused permanent phenotypic changes. Specifically, a transient suppression of
      cortactin was achieved in immature neurons with a single exposure to antisense
      oligonucleotides. This inhibition first induced both the expression of mRNA and
      the enzymatic activity of GAD significantly earlier than in control neurons.
      Second, cortactin-suppressed large projectional neurons exhibited significantly
      shorter processes and growth cones with protrusive filopodia and an enlarged
      lamellipodia veil. Most importantly, this remodeling of neuritic outgrowth in
      projectional somata was accompanied by the ectopic induction of GABA (*
      aminobutyric acid) expression. Considering this data altogether, it appears that
      cortactin may function to suppress concurrently several parameters of the
      GABAergic program in large developing neurons.

PMID- 10954416
TI  - Overexpression of PAX6(5a) in lens fiber cells results in cataract and
      upregulation of (alpha)5(beta)1 integrin expression.
AB  - The PAX6 gene, a key regulator of eye development, produces two major proteins
      that differ in paired domain structure: PAX6 and PAX6(5a). It is known that an
      increase in the PAX6(5a) to PAX6 ratio leads to multiple ocular defects in
      humans. Here, transgenic mice were created that overexpress human PAX6(5a) in the
      lens. These mice develop cataracts with abnormalities in fiber cell shape as well
      as fiber cell/lens capsule and fiber cell/fiber cell interactions. While the
      structure of the actin cytoskeleton appeared relatively normal, the cataractous
      lens expresses increased amounts of paxillin and p120(ctn) as well as large
      aggregates of (alpha)5(beta)1 integrin in the dysgenic fiber cells. The elevated
      amounts of these proteins in the transgenic lens correlated well with elevated
      levels of their respective mRNAs. To investigate the role of Pax-6(5a) in the
      upregulation of these genes, a series of gel shift experiments using truncated
      proteins and consensus oligonucleotides demonstrated the complexity of Pax-6 and
      Pax-6(5a) binding to DNA, aiding our identification of potential binding sites in
      the human (&agr;)5- and (beta)1-integrin promoters. Consequent gel shift analysis
      demonstrated that these putative regulatory sequences bind Pax-6 and/or Pax-6(5a)
      in lens nuclear extracts, suggesting that the human (alpha)5 and (beta)1 integrin
      promoters contain PAX6/PAX6(5a) binding sites and maybe directly regulated by
      this transcription factor in the transgenic lens. We conclude that these
      transgenic mice are good models to study a type of human cataract and for
      identifying batteries of genes that are directly or indirectly regulated by both
      forms of Pax-6.

PMID- 10954417
TI  - Protein kinase C activation leads to dephosphorylation of occludin and tight
      junction permeability increase in LLC-PK1 epithelial cell sheets.
AB  - Activation of protein kinase C by exposure of LLC-PK1 renal epithelial cells to
      10(-7) M TPA, a tumor promoting phorbol ester, results in a rapid and sustained
      increase in paracellular permeability as evidenced by a decrease in
      transepithelial electrical resistance. Occludin, the first identified
      transmembrane protein to be localized to the tight junction of both epithelial
      and endothelial cells is thought play an important role in tight junction
      barriers. Although transepithelial electrical resistance fell to less than 20% of
      initial values within 1 hour of TPA exposure, transmission electron microscopy
      showed no change in the gross morphology of the tight junction of cells treated
      with 10(-7) M TPA for up to 2 hours. Immunofluorescence microscopy revealed a
      more rapid change in the membrane distribution of ZO-1 compared to occludin in
      the TPA-treated cells. Immunoblot analysis indicated that occludin levels in
      total cell lysates as well as cytosolic, membrane (Triton-X soluble) and
      cytoskeletal (Triton-X insoluble) fractions remained unchanged for at least 2
      hours in cells treated with 10(-7) M TPA compared to their corresponding control
      cells. As the phosphorylation state of occludin is thought to be important in
      both tight junction assembly and regulation, the effect of phorbol ester
      treatment on the phosphorylation of occludin was investigated. Surprisingly,
      activation of protein kinase C with 10(-7) M TPA resulted in a time-dependent
      decrease in threonine phosphorylation of occludin which correlated closely with
      the rapid decrease in transepithelial electrical resistance. This
      dephosphorylation of occludin, occurring after activation of a serine/threonine
      kinase by TPA, suggested that protein kinase C was not acting directly on this
      tight junction target protein. If occludin dephosphorylation is involved in
      increasing tight junction permeability, then protein kinase C is apparently
      further upstream in the signaling pathway regulating epithelial barrier function,
      with a downstream serine/threonine phosphatase acting upon occludin.

PMID- 10954418
TI  - Membrane localization and biological activity of SNAP-25 cysteine mutants in
      insulin-secreting cells.
AB  - The tSNARE SNAP-25 is expressed in pancreatic (beta)-cells and is involved in the
      regulated release of insulin. It has been shown previously that SNAP-25
      associates with the plasma membrane consequent to palmitoylation of one or more
      cysteines in the central region of the molecule. The importance of palmitolyation
      in the biological function of SNAP-25 in exocytosis was not addressed.
      Furthermore, studies on both SNAP-25 and its non-palmitoylated homologues SNAP-29
      and sec9, have suggested an alternative or complementary mechanism for membrane
      association involving interaction with syntaxin. To address these issues, we have
      now studied the behavior and biological activity of cysteine mutant SNAP-25 in
      insulin-secreting (HIT) cells. While 91% of native SNAP-25 was associated with
      the membrane, this value decreased to 56% for the single cysteine mutant C85/A
      and to 10% for the double (C85,88/A) and quadruple (C85,88,90,92/A) mutants. The
      mutant SNAP-25 forms were all found to bind syntaxin 1A with equal efficacy. Over
      expression of syntaxin 1A in HIT cells allowed for partial relocalization of both
      the double and quadruple SNAP-25 cys mutants to the membrane. By introducing a
      further mutation to the SNAP-25 molecules to render them resistant to botulinum
      neurotoxin E, it was possible to study their ability to reconstitute regulated
      insulin secretion in toxin-treated HIT cells. Native SNAP-25 was able to fully
      reconstitute secretory activity in such cells. Despite the fact that the single
      cysteine mutant was significantly displaced to the cytosol, it still displayed
      82% activity in the secretion reconstitution assay, and a similar discrepancy was
      seen for the double mutant. Even the quadruple mutant with no remaining cysteines
      was able to support a minimal level of secretion. It is concluded that both
      palmitoylation and binding to syntaxin are implicated in membrane association of
      SNAP-25. This as well as the discrepancy between membrane localization and
      biological activity of the cysteine mutants, suggests a complex, multi-component
      process for association of SNAP-25 with the membrane and its recruitment to a
      biologically productive state.

PMID- 10954420
TI  - Phosphorylation of histone H3 is correlated with changes in the maintenance of
      sister chromatid cohesion during meiosis in maize, rather than the condensation
      of the chromatin.
AB  - Meiotic chromosome condensation is a unique process, characterized by dramatic
      changes in chromosome morphology that are required for the correct progression of
      pairing, synapsis, recombination and segregation of sister chromatids. We used an
      antibody that recognizes a ser 10 phosphoepitope on histone H3 to monitor H3
      phosphorylation during meiosis in maize meiocytes. H3 phosphorylation has been
      reported to be an excellent marker for chromosome condensation during mitotic
      prophase in animal cells. In this study, we find that on maize mitotic
      chromosomes only pericentromeric regions are stained; there is little staining on
      the arms. During meiosis, chromosome condensation from leptotene through
      diplotene occurs in the absence of H3 phosphorylation. Instead, the changes in H3
      phosphorylation at different stages of meiosis correlate with the differences in
      requirements for sister chromatid cohesion at different stages. Just before
      nuclear envelope breakdown, histone H3 phosphorylation is seen first in the
      pericentromeric regions and then extends through the arms at metaphase I; at
      metaphase II only the pericentromeric regions are stained. In afd1 (absence of
      first division), a mutant that is defective in many aspects of meiosis including
      sister chromatid cohesion and has equational separation at metaphase I, staining
      is restricted to the pericentromeric regions during metaphase I and anaphase I;
      there is no staining at metaphase II or anaphase II. We conclude that changes in
      the level of phosphorylation of ser10 in H3 correspond to changes in the cohesion
      of sister chromatids rather than the extent of chromosome condensation at
      different stages of meiosis.

PMID- 10954419
TI  - Novel generation of human satellite DNA-based artificial chromosomes in mammalian
      cells.
AB  - An in vivo approach has been developed for generation of artificial chromosomes,
      based on the induction of intrinsic, large-scale amplification mechanisms of
      mammalian cells. Here, we describe the successful generation of prototype human
      satellite DNA-based artificial chromosomes via amplification-dependent de novo
      chromosome formations induced by integration of exogenous DNA sequences into the
      centromeric/rDNA regions of human acrocentric chromosomes. Subclones with
      mitotically stable de novo chromosomes were established, which allowed the
      initial characterization and purification of these artificial chromosomes.
      Because of the low complexity of their DNA content, they may serve as a useful
      tool to study the structure and function of higher eukaryotic chromosomes. Human
      satellite DNA-based artificial chromosomes containing amplified satellite DNA,
      rDNA, and exogenous DNA sequences were heterochromatic, however, they provided a
      suitable chromosomal environment for the expression of the integrated exogenous
      genetic material. We demonstrate that induced de novo chromosome formation is a
      reproducible and effective methodology in generating artificial chromosomes from
      predictable sequences of different mammalian species. Satellite DNA-based
      artificial chromosomes formed by induced large-scale amplifications on the short
      arm of human acrocentric chromosomes may become safe or low risk vectors in gene
      therapy.

PMID- 10954421
TI  - Clathrin-mediated endocytosis and recycling of autocrine motility factor receptor
      to fibronectin fibrils is a limiting factor for NIH-3T3 cell motility.
AB  - Autocrine motility factor receptor (AMF-R) is internalized via a clathrin
      independent pathway to smooth endoplasmic reticulum tubules. This endocytic
      pathway is shown here to be inhibited by methyl-(beta)-cyclodextrin (m(beta)CD)
      implicating caveolae or caveolae-like structures in AMF internalization to smooth
      ER. AMF-R is also internalized via a clathrin-dependent pathway to a transferrin
      receptor-negative, LAMP-1/lgpA-negative endocytic compartment identified by
      electron microscopy as a multivesicular body (MVB). Endocytosed AMF recycles to
      cell surface fibrillar structures which colocalize with fibronectin; AMF-R
      recycling is inhibited at 20 degrees C, which blocks endocytosis past the early
      endosome, but not by m(beta)CD demonstrating that AMF-R recycling to fibronectin
      fibrils is mediated by clathrin-dependent endocytosis to MVBs. Microtubule
      disruption with nocodazole did not affect delivery of bAMF to cell surface
      fibrils indicating that recycling bAMF traverses the MVB but not a later
      endocytic compartment. Plating NIH-3T3 cells on an AMF coated substrate did not
      specifically affect cell adhesion but prevented bAMF delivery to cell surface
      fibronectin fibrils and reduced cell motility. AMF-R internalization and
      recycling via the clathrin-mediated pathway are therefore rate-limiting for cell
      motility. This recycling pathway to the site of deposition of fibronectin may be
      implicated in the de novo formation of cellular attachments or the remodeling of
      the extracellular matrix during cell movement.

PMID- 10954422
TI  - Biochemical characterization and localization of the dual specificity kinase
      CLK1.
AB  - CLK1 was one of the first identified dual specificity kinases and is the founding
      member of the 'LAMMER' family of kinases. We have established the substrate site
      specificity of CLK1. We report here that truncation of the N terminus of CLK1
      resulted in a dramatic increase in CLK1 enzymatic activity, indicating that the N
      terminus acts as a negative regulatory domain. The N-terminal truncation resulted
      in a 45-fold increase in V(max), suggesting that this domain does not contain a
      pseudo-substrate motif, but may act to conformationally constrain the catalytic
      activity of CLK1. Tyrosine phosphorylation has been proposed to be critical for
      CLK1 activity, however, CLK1 activity was unaffected by exposure to tyrosine
      phosphatases. Treatment of CLK1 with the serine/threonine specific phosphatase
      PP2A, resulted in a 2- to 6-fold increase in enzymatic activity. Incubation of
      CLK1 with tyrosine phosphatases in combination with PP2A abolished CLK1 activity.
      These data suggest that CLK1 is regulated by three distinct mechanisms that serve
      to both positively and negatively regulate CLK1 activity. CLK1 activity is
      positively regulated by phosphorylation on either tyrosine residues or
      serine/threonine residues, and is negatively regulated by steric constraints
      mediated by the N-terminal domain, as well as, by phosphorylation on a subset of
      serine/threonine residues within the catalytic domain. CLK1 mRNA is expressed at
      low levels in all tissues and cell lines examined. The full-length and truncated
      splice forms are expressed at roughly equivalent levels in most tissues. The
      ratio of the two splice variants of CLK1 can be altered by treatment with
      cycloheximide. CLK1 protein expression is limited to a small subset of highly
      localized neuronal populations in the rat brain. Contrary to previous studies
      using overexpression systems, we show that CLK1 protein is primarily found in the
      cytoplasm of these cells, with only a small fraction localized to the nucleus.

PMID- 10954423
TI  - Fc receptor mediated endocytosis of small soluble immunoglobulin G immune
      complexes in Kupffer and endothelial cells from rat liver.
AB  - Soluble circulating immunoglobulin G immune complexes are mainly eliminated by
      the liver, predominantly by uptake in the Kupffer cells, but also the liver
      endothelial cells seem to be of importance. In the present study we have followed
      the intracellular turnover of immune complexes after Fc(gamma) receptor mediated
      endocytosis in cultured rat liver endothelial cells and Kupffer cells by means of
      isopycnic centrifugation, DAB cross-linking and morphological techniques. For the
      biochemical experiments the antigen, dinitrophenylated bovine serum albumin
      (BSA), was labeled with radioiodinated tyramine cellobiose that cannot cross
      biological membranes and therefore traps labeled degradation products at the site
      of formation. The endocytic pathway followed by immune complexes was compared
      with that followed by scavenger receptor ligands, such as formaldehyde treated
      BSA and dinitrophenylated BSA, and the mannose receptor ligand ovalbumin. Both
      Kupffer cells and liver endothelial cells took up and degraded the immune
      complexes, but there was a clear delay in the degradation of immune complexes as
      compared to degradation of ligands taken up via scavenger receptors. The kinetics
      of the endocytosis of scavenger receptor ligand was unaffected by simultaneous
      uptake of immune complexes. Experiments using both biochemical and morphological
      techniques indicated that the delayed degradation was due to a late arrival of
      the immune complexes at the lysosomes, which partly was explained by
      retroendocytosis of immune complexes. Electron microscopy studies revealed that
      the immune complexes were retained in the early endosomes that remained
      accessible to other endocytic markers such as ovalbumin. In addition, the immune
      complexes were seen in multivesicular compartments apparently devoid of other
      endocytic markers. Finally, the immune complexes were degraded in the same
      lysosomes as the ligands of scavenger receptors. Thus, immune complexes seem to
      follow an endocytic pathway that is kinetically or maybe morphologically
      different from that followed by scavenger and mannose receptor ligands.

PMID- 10954424
TI  - The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a
      binding partner for the Rho GTPases Cdc42 and Rac1.
AB  - A mammalian homologue of the PDZ domain containing Caenorhabditis elegans protein
      PAR-6 was found in a yeast two-hybrid system screen as binding to the Rho family
      member Cdc42. PAR-6 contains a PDZ domain and in C. elegans it has been shown to
      be crucial for the asymmetric cleavage and establishment of cell polarity during
      the first cell divisions in the growing embryo. Mammalian PAR-6 interacted with
      Cdc42 and Rac1 both in the yeast two-hybrid system and in in vitro binding
      assays. Co-immunoprecipitation experiments, employing transiently transfected Cos
      1 cells, further confirmed that Cdc42 and Rac1 are physiological binding partners
      for PAR-6. We found that, in epithelial Madin-Darby canine kidney cells (MDCK),
      endogenous PAR-6 was present in the tight junctions, as judged from its co
      localisation with the tight junction protein ZO-1, however, PAR-6 was also
      detected in the cell nucleus. Stimulation of MDCK cells with scatter
      factor/hepatocyte growth factor induced a loss of PAR-6 from the areas of cell
      cell contacts in conformity with their progressive breakdown. In C. elegans PAR-6
      co-localises with PAR-3 and has been suggested to form a direct complex. In
      agreement with earlier studies, mammalian PAR-3 was found to be present in tight
      junctions of MDCK cells but, in contrast to PAR-6, the protein could not be
      detected in the nucleus. Furthermore, co-immunoprecipitation experiments,
      employing Cos-1 cells, demonstrated that mammalian PAR-6 and PAR-3 formed a
      direct complex. These findings, together with the reported roles of PAR-6 and PAR
      3 in C. elegans, suggest that Cdc42 and Rac1 and PAR-6/PAR-3 are involved in the
      establishment of cell polarity in epithelial cells.

PMID- 10954425
TI  - Mutations of arginine residues within the 146-KKRRK-150 motif of the ActA protein
      of Listeria monocytogenes abolish intracellular motility by interfering with the
      recruitment of the Arp2/3 complex.
AB  - The recruitment of actin to the surface of intracellular Listeria monocytogenes
      and subsequent tail formation is dependent on the expression of the bacterial
      surface protein ActA. Of the different functional domains of ActA identified thus
      far, the N-terminal region is absolutely required for actin filament recruitment
      and intracellular motility. Mutational analysis of this domain which abolished
      actin recruitment by intracellular Listeria monocytogenes identified two arginine
      residues within the 146-KKRRK-150 motif that are essential for its activity. More
      specifically, recruitment of the Arp2/3 complex to the bacterial surface, as
      assessed by immunofluorescence staining with antibodies raised against the p21
      Arc protein, was not obtained in these mutants. Consistently, treatment of
      infected cells with latrunculin B, which abrogated actin filament formation, did
      not affect association of ActA with p21-Arc at the bacterial surface. Thus, the
      initial recruitment of the Arp2/3 complex to the bacterial surface is independent
      of, and precedes, actin polymerisation. Our data suggest that binding of the
      Arp2/3 complex is mediated by specific interactions dependent on arginine
      residues within the 146-KKRRK-150 motif present in ActA.

PMID- 10954426
TI  - The lysosomal protease cathepsin D is efficiently sorted to and secreted from
      regulated secretory compartments in the rat basophilic/mast cell line RBL.
AB  - Basophils and mast cells contain a peculiar class of inflammatory granules that
      discharge their content upon antigen-mediated crosslinking of IgE-membrane
      receptors. The pathways for granule biogenesis and exocytosis in these cells are
      still largely obscure. In this study we employed the rat basophilic leukemia
      (RBL)/mast cell line to verify the hypothesis that inflammatory granules share
      common bioactive molecules and functional properties with lysosomes. We
      demonstrate that inflammatory granules, as identified by the monoclonal 5G10
      antibody (which recognises an integral membrane protein) or by Toluidine Blue
      staining, have an intralumenal acidic pH, possess lysosomal enzymes and are
      accessible by fluid-phase and membrane endocytosis markers. In addition, we
      studied the targeting, subcellular localisation and regulated secretion of the
      lysosomal aspartic protease cathepsin D (CD) as affected by IgE receptor
      stimulation in order to obtain information on the pathways for granule biogenesis
      and exocytosis. Stimulation with DNP-BSA of specific IgE-primed RBL cells led to
      a prompt release of processed forms of CD, along with other mature lysosomal
      hydrolases. This release could be prevented by addition of EGTA, indicating that
      it was dependent on extracellular calcium influx. Antigen stimulation also
      induced exocytosis of immature CD forms accumulated by ammonium chloride,
      suggesting the existence of an intermediate station in the pathway for granule
      biogenesis still sensitive to regulated exocytosis. The targeting of molecules to
      secretory granules may occur via either a mannose-6-phosphate-dependent or
      mannose-6-phosphate-independent pathway. We conclude that endosomes and lysosomes
      in basophils/mast cells can act as regulated secretory granules or actually
      identify with them.

PMID- 10954427
TI  - Implication of sphingolipid metabolism in the stability of the Golgi apparatus.
AB  - We examined the effects of short chain and long chain ceramides on the stability
      of the Golgi apparatus. Short chain ceramides, C(2)- and C(6)-ceramides, blocked
      brefeldin A-induced Golgi disassembly without affecting the rapid release of
      Golgi coat proteins, whereas they did not inhibit brefeldin A-induced tubulation
      of endosomes. Both short chain ceramides also retarded Golgi disassembly induced
      by nordihydroguaiaretic acid and nocodazole, suggesting that they stabilize the
      Golgi apparatus. In contrast to short chain ceramides, natural long chain
      ceramides, when incorporated into cells or formed within cells upon treatment
      with sphingomyelinase or metabolic inhibitors, enhanced brefeldin A-induced Golgi
      disassembly. These results suggest that sphingolipid metabolism is implicated in
      the stability of the Golgi apparatus.

PMID- 10954428
TI  - A novel EH domain protein of Saccharomyces cerevisiae, Ede1p, involved in
      endocytosis.
AB  - Sequencing of the entire genome of S. cerevisiae has revealed the existence of
      five proteins containing EH domains. These are protein-protein interaction
      modules first described in mammalian Eps15, a protein that is involved in
      clathrin-dependent endocytosis. Two of the yeast proteins, End3p and Pan1p, are
      required for the internalization step of endocytosis. We report characterization
      of the nonessential ORF YBL047c which, like Eps15, encodes a protein with three N
      terminal EH domains. Deletion of YBL047c leads to a defective fluid-phase
      endocytosis and to defective internalization of the pheromone (alpha)-factor and
      uracil permease. We therefore named YBL047c EDE1, for EH Domains and Endocytosis.
      Ede1p expressed as a chromosomally encoded fusion to the green fluorescent
      protein is localized in punctate cortical spots that only partially colocalize
      with actin patches. This localization is maintained when actin is depolymerized.
      Deletion of EDE1 impairs the diploid budding pattern, but has only a small impact
      on actin cytoskeleton organization, in contrast to the effects observed in pan1
      cells and many end mutants impaired in proteins colocalizing with cortical actin
      patches. Genetic interaction was observed between EDE1 and RSP5, which encodes
      the ubiquitin ligase Rsp5p essential for ubiquitin-dependent endocytosis of many
      plasma membrane proteins, thus further emphasizing the functional link between
      Rsp5p and the EH domain proteins. We also observed genetic interaction between
      EDE1, and END3 or PAN1, suggesting that Ede1p might be part of a yeast EH network
      implicated in endocytosis.

PMID- 10954429
TI  - Flagellum ontogeny in trypanosomes studied via an inherited and regulated RNA
      interference system.
AB  - The African trypanosome, Trypanosoma brucei possesses a large and unique
      intraflagellar structure called the paraflagellar rod (PFR). The PFR is composed
      of 2 major proteins, PFRA and PFRC. We have generated an inducible mutant
      trypanosome cell line (snl-2) that expresses linked inverted copies of a PFRA
      gene, capable of forming a PFRA double-stranded (ds) RNA. When expression of this
      dsRNA was induced, new PFRA RNA and PFRA protein quickly disappeared and PFR
      construction was affected, resulting in cell paralysis. This inducible RNA
      interference (RNAi) effect was fast-acting, heritable and reversible. It allowed
      us to demonstrate that PFR proteins are able to enter both mature and growing
      flagella but appear to concentrate differentially in new flagella because of the
      construction process. The PFR is constructed by a polar assembly process at the
      distal end of the flagellum resulting in a stable cytoskeletal structure with low
      turn-over. The inducible RNAi approach will have widespread applicability in
      studies of gene function and cellular processes in parasites.

PMID- 10954430
TI  - Actinin-4 is preferentially involved in circular ruffling and macropinocytosis in
      mouse macrophages: analysis by fluorescence ratio imaging.
AB  - We have applied fluorescence ratio imaging to the analysis of an actin-binding
      protein concentration relative to F-actin in macrophages, in order to explore the
      role of a novel (alpha)-actinin isoform, actinin-4, relative to that of the
      classical isoform, actinin-1. Conventional immunofluorescence images showed that
      both isoforms were enriched in F-actin-rich regions such as cell surface ruffles.
      However, ratio images further demonstrated that actinin-4 concentrations relative
      to F-actin were higher in peripheral inward curved ruffles and dorsal circular
      ruffles, presumed precursor forms of macropinosomes, than in straight linear
      ruffles, while actinin-1 concentrations were uniform among the different types of
      ruffles. Macropinosome pulse-labeling and chase experiments indicated that
      actinin-4 was also closely associated with newly formed macropinosomes and
      gradually dissociated with their maturation. Consistent with ratio imaging data,
      macrophages scrape-loaded with anti-actinin-4 showed a more reduced rate of
      macropinocytosis than those loaded with anti-actinin-1. Altogether, these results
      indicate that actinin-4 and actinin-1 contribute differently to F-actin dynamics,
      that actinin-4 is more preferentially involved in early stages of
      macropinocytosis than actinin-1. A similar redistribution of actinin-4 was also
      observed during phagocytosis, suggesting that actinin-4 may play the same role in
      the two mechanistically analogous types of endocytosis, i.e. macropinocytosis and
      phagocytosis.

PMID- 10954431
TI  - Failure of pronuclear migration and repeated divisions of polar body nuclei
      associated with MTOC defects in polo eggs of Drosophila.
AB  - The meiotic spindle of Drosophila oocytes is acentriolar but develops an unusual
      central microtubule organising centre (MTOC) at the end of meiosis I. In polo
      oocytes, this common central pole for the two tandem spindles of meiosis II was
      poorly organised and in contrast to wild-type failed to maintain its associated
      Pav-KLP motor protein. Furthermore, the polar body nuclei failed to arrest at
      metaphase, and the four products of female meiosis all underwent repeated haploid
      division cycles on anastral spindles. This was linked to a failure to form the
      astral array of microtubules with which the polar body chromosomes are normally
      associated. The MTOC associated with the male pronucleus was also defective in
      polo eggs, and the sperm aster did not grow. Migration of the female pronucleus
      did not take place and so a gonomeric spindle could not form. We discuss these
      findings in relation to the known roles of polo like kinases in regulating the
      behaviour of MTOCs.

PMID- 10954433
TI  - Radiologic evaluation of soft-tissue masses: a current perspective.

PMID- 10954432
TI  - The sound of bones: sonography of the musculoskeletal system.

PMID- 10954434
TI  - The impact of imaging: a personal recollection.

PMID- 10954435
TI  - Productivity of radiologists in 1997: estimates based on analysis of resource
      based relative value units.
AB  - OBJECTIVE: Productivity of radiologists was quantified using the resource-based
      relative value scale for examining trends in workload. MATERIALS AND METHODS:
      Staffing and workload data for 1997 were collected in a survey of radiology
      departments in multispecialty clinics. Workload ratios were calculated and were
      compared with prior surveys of the same clinics and with published data. RESULTS:
      Fifteen clinics reported 3,234,730 examinations and 1,860,729 resource-based
      relative value units (RBRVUs) performed by 284 radiologists and 28 fellows
      serving 6305 providers. Productivity ratios were as follows: physician index, 19
      physicians per radiologist; provider index, 23 providers per radiologist;
      availability index, 0.78; difficulty index, 0.54 RBRVUs per examination;
      examination index, 11,559 examinations per year per radiologist; RBRVU index,
      6090 RBRVUs per year per radiologist. Each index had roughly a twofold range of
      variation from lowest to highest ratio observed. Among diagnostic and
      interventional procedures, 37% of the supervision and interpretation RBRVUs were
      in general radiography, 41% in sectional imaging, and 22% in special procedures.
      Since 1973, the percentages of sectional imaging and special procedure
      examinations and RBRVUs have increased, and the difficulty index has increased.
      The physician index has been relatively stable. Non-supervision and
      interpretation codes constitute approximately 18% of the reported RBRVUs. RBRVU
      valuation of total radiology services has held steady or slightly increased
      between 1993 and 1997. CONCLUSION: RBRVU workload of radiologists in the clinics
      appears to be increasing primarily because of an increase in the percentages of
      highly valued sectional imaging and interventional and angiographic studies,
      which constituted 63% of the diagnostic imaging RBRVU workload. The ranges of the
      indexes among the clinics varies greatly.

PMID- 10954436
TI  - The treatment of acute pneumonias with roentgen rays.

PMID- 10954437
TI  - Hindsight bias.

PMID- 10954438
TI  - Sample size tables for receiver operating characteristic studies.
AB  - OBJECTIVE: I provide researchers with tables of sample size for multiobserver
      receiver operating characteristic (ROC) studies that compare the diagnostic
      accuracies of two imaging techniques. MATERIALS AND METHODS: I computed the
      number of patients and observers needed as a function of five parameters: the
      measure of diagnostic accuracy (area under the ROC curve, sensitivity at a false
      positive rate </= 0.10, or specificity at a false-negative rate </= 0.10),
      conjectured level of accuracy, suspected difference in accuracy between the two
      imaging techniques, observer variability, and ratio of patients without to
      patients with the condition. RESULTS: The numbers of patients and observers
      required vary dramatically with these five parameters, increasing with more
      refined measures of accuracy, with lower accuracy levels, with smaller suspected
      differences, with greater observer variability, and with less balanced designs.
      The number of patients required for a study can be reduced by increasing the
      number of observers, and vice versa. When the intra- and interobserver
      variability is large, a study design with just four observers is usually
      inadequate. CONCLUSION: Many factors must be considered when determining the
      appropriate sample sizes for multiobserver ROC studies. My tables serve only as
      initial ballpark estimates. Investigators should compute sample size using
      parameters that reflect their clinical application.

PMID- 10954439
TI  - Interactive software for generation and visualization of structured findings in
      radiology reports.
AB  - OBJECTIVE: Our objectives were to develop a user-friendly graphic interface for a
      module that integrates traditional radiology reporting, natural language
      processing, and editing capabilities; to facilitate the structuring of radiology
      reports as part of routine clinical practice; to use a commercial speech
      recognition module for online transcription; and to implement the module in a
      hardware-independent environment. CONCLUSION: After implementation, the module
      was tested with 150 chest radiology reports by two radiologists and assessed for
      ease of use and accuracy. Overall, accuracy was close to 90% and user
      satisfaction was high. When radiology reports are structured as a part of routine
      clinical practice, it is possible to accomplish intelligent indexing and
      retrieval to facilitate teaching and research.

PMID- 10954440
TI  - MR imaging of disorders of the Achilles tendon.

PMID- 10954442
TI  - Barton R. Young, 1904-2000

PMID- 10954441
TI  - MR imaging of disorders of the posterior tibialis tendon.

PMID- 10954443
TI  - An illustrated tutorial of musculoskeletal sonography: part I, introduction and
      general principles.

PMID- 10954444
TI  - Unilateral glenoid hypoplasia: unusual findings on MR arthrography.

PMID- 10954445
TI  - Morton's neuroma: is it always symptomatic?
AB  - OBJECTIVE: We determined the prevalence of clinically silent Morton's neuroma and
      searched for distinguishing MR imaging features of Morton's neuroma in patients
      with clinical complaints related to this entity and in patients with clinically
      silent lesions. MATERIALS AND METHODS: One radiologist who was unaware of
      clinical findings retrospectively reviewed 85 consecutive foot MR examinations.
      MR imaging criteria for Morton's neuroma included a low- to intermediate-signal
      intensity soft-tissue mass in the intermetatarsal space. The size, location, and
      signal intensity of each neuroma and the presence of intermetatarsal bursae were
      recorded. The patients were subdivided into symptomatic or asymptomatic groups on
      the basis of the patients' answers on a questionnaire documenting the locations
      and characteristics of symptoms and discussions with each referring physician
      about clinical findings. Surgical confirmation was available in eight of 25
      symptomatic patients. RESULTS: The prevalence of Morton's neuroma in patients
      with no clinical evidence of this condition was 33% (19/57). Twenty-five patients
      had symptomatic Morton's neuroma, 19 had Morton's neuroma based on MR imaging
      findings with no clinical manifestations, and 41 did not have Morton's neuroma.
      Slightly larger lesions were observed in the symptomatic group, although
      significant overlap was noted between the two groups. The mean transverse
      diameter of symptomatic neuromas was 5.3 mm (standard deviation, 2.14) compared
      with 4.1 mm (standard deviation, 1.75) for asymptomatic neuromas; this difference
      was marginally significant (p = 0.05). CONCLUSION: The MR imaging diagnosis of
      Morton's neuroma does not imply symptomatology. Careful correlation between
      clinical and MR imaging findings is mandatory before Morton's neuroma is
      considered clinically relevant.

PMID- 10954446
TI  - Carpal tunnel syndrome caused by tophaceous gout: CT and MR imaging features in
      20 patients.
AB  - OBJECTIVE: The objective of this study is to describe the CT and MR imaging
      findings of gouty tophi in the wrist and present this entity as a cause of carpal
      tunnel syndrome. MATERIALS AND METHODS: Retrospective review of the CT (n = 18)
      and MR imaging (n = 20) studies of the wrist in patients with a documented
      diagnosis of gout who presented with gout-related carpal tunnel syndrome was
      performed; images of 24 wrists were collected over a 5-year period. Patient
      population included 20 men, who ranged in age from 35 to 76 years. All images
      were reviewed by two musculoskeletal radiologists who reached a consensus
      opinion. Surgical correlation was available in 12 patients. RESULTS: Tophi were
      found in the floor of the carpal tunnel (n = 18), carpal bones (n = 17),
      radiocarpal joint (n = 17), and extensor tendons or tendon sheaths (n = 16) of
      the wrist. All tophi showed similar signal characteristics (from low to
      intermediate signal intensity on T1-weighted images with heterogeneous signal
      intensity on T2-weighted images) with the exception of tophi in the floor of the
      carpal tunnel (low signal intensity on T2-weighted images). Varying degrees of
      calcification were noted on CT and MR imaging studies. Gadolinium-enhanced MR
      studies showed heterogeneous enhancement. CONCLUSION: Gouty tophi should be
      entertained as a cause of carpal tunnel syndrome in the appropriate patient
      population. Familiarity with this entity and its imaging characteristics may
      prove helpful in diagnosis and preoperative planning.

PMID- 10954447
TI  - MR imaging findings in spinal ligamentous injury.

PMID- 10954448
TI  - MR arthrography of the labral capsular ligamentous complex in the shoulder:
      imaging variations and pitfalls.
AB  - OBJECTIVE: Using MR arthrography, we examined normal anatomy, anatomic
      variations, and pitfalls of imaging the labral capsular ligamentous complex in
      the asymptomatic shoulder. SUBJECTS AND METHODS: We obtained 108 MR arthrograms
      of the glenohumeral joint in 95 asymptomatic volunteers with axial (108
      shoulders) and oblique coronal (56 shoulders) images. We examined labral shape,
      patterns of capsular insertion, presence or absence of glenohumeral ligaments,
      and pitfalls of imaging. Our patients were men (auxiliary policemen) between 19
      and 24 years old (mean age, 21 years). RESULTS: The shapes of labra were
      triangular (anterior part, 64%; posterior part, 47%), round (17%; 33%), flat (2%;
      17%), cleaved (11%; 1%), notched (3%; 0%), or absent (2%; 2%). Using the system
      of Mosely and Overgaard, the anterior capsular insertion was type 1 in 63% of
      shoulders, type 2 in 20%, and type 3 in 17%; the posterior capsular insertion was
      type 1 in 60% of shoulders, type 2 in 31%, and type 3 in 9%. The superior and
      inferior glenohumeral ligaments were present in 99% of shoulders, but the middle
      glenohumeral ligament was present in only 79%. We also detected many pitfalls of
      MR imaging in identifying findings such as the undercutting of the labrum by
      cartilage (32% of shoulders), prominent axillary folds (46%), sublabral holes
      (7%) or recesses (33%), Buford complexes (2%), and sulci between the biceps
      tendon and superior labrum (30%). CONCLUSION: Knowledge of normal anatomy and
      anatomic variations of the labral complex is important for the examination of the
      shoulder with MR arthrography.

PMID- 10954449
TI  - Radiologic-pathologic correlation of intraosseous lipomas.

PMID- 10954450
TI  - Multiphase hepatic CT with a multirow detector CT scanner.
AB  - OBJECTIVE: The aim of this study was to evaluate a new injection-acquisition
      technique performed using a multirow detector CT scanner for separation of three
      distinct hepatic circulatory phases (hepatic artery, portal venous inflow,
      hepatic venous) and to determine which of these phases is optimal for detecting
      hypervascular neoplasm. MATERIALS AND METHODS: Two sequential acquisitions were
      performed during a single breath-hold followed by a third acquisition beginning
      60 sec after injection. Injection-to-scan delay for the first acquisition was the
      individual patient's circulation time, which was determined by a preliminary mini
      bolus. The mean attenuation of the upper abdominal aorta, portal vein, and
      hepatic parenchyma were determined for each imaging pass in 20 patients with
      cirrhosis and 20 patients without cirrhosis. Tumor-to-liver contrast for
      hypervascular primary and metastatic neoplasm was evaluated in a different set of
      16 cirrhotic patients and nine noncirrhotic patients. Three-dimensional CT
      arteriograms were obtained from first-pass data. RESULTS: Three distinct
      circulatory phases (hepatic artery, portal vein inflow or late arterial, and
      hepatic venous) were seen in cirrhotic and noncirrhotic patients. Maximum tumor
      to-liver contrast for hypervascular primary and metastatic neoplasm occurred
      during the second pass for both cirrhotic (p < 0.006) and noncirrhotic (p < 0.
      001) patients. A three-dimensional hepatic-mesenteric CT arteriogram of normal or
      anomalous hepatic vessels without venous overlay was obtained from first-pass
      data in all patients. CONCLUSION: Rapid-sequence hepatic helical CT allows
      selection of the optimal time interval for hypervascular tumor detection. A new
      paradigm for rapid hepatic CT acquisition-namely, hepatic arterial, portal vein
      inflow, and hepatic venous phases-is recommended to replace hepatic artery
      dominant and portal venous phases.

PMID- 10954451
TI  - CT and MR imaging findings in focal nodular hyperplasia of the liver: radiologic
      pathologic correlation.

PMID- 10954452
TI  - Detection of hepatocellular carcinomas and dysplastic nodules in cirrhotic
      livers: accuracy of helical CT in transplant patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic efficacy of
      three-phase helical dynamic CT in the detection and characterization of
      hepatocellular carcinomas and dysplastic nodules in cirrhotic livers. SUBJECTS
      AND METHODS: Three-phase helical dynamic CT in 41 patients with liver cirrhosis
      was evaluated prospectively before orthotopic liver transplantation. The numbers
      of hepatocellular carcinomas and dysplastic nodules were assessed in the
      explanted livers and compared with pretransplantation CT findings. RESULTS:
      Examination of the explanted livers revealed 21 hepatocellular carcinomas in 15
      patients and 23 dysplastic nodules in 10 patients. The size of the hepatocellular
      carcinomas was 0.6-5. 0 cm (mean, 1.9 cm), and that of the dysplastic nodules was
      0.7-2.0 cm (mean, 1.0 cm). The use of helical dynamic CT enabled detection of 15
      of 21 hepatocellular carcinomas (sensitivity, 71%) and nine of 23 dysplastic
      nodules (sensitivity, 39%). Patient sensitivity and specificity in the detection
      of hepatocellular carcinomas were 80% (12/15) and 96% (25/26), respectively, and
      for dysplastic nodules, 50% (5/10) and 97% (30/31), respectively. CONCLUSION:
      Three-phase helical dynamic CT is relatively insensitive for detection of
      hepatocellular carcinomas and dysplastic nodules in cirrhotic livers, especially
      for dysplastic nodules and hepatocellular carcinomas smaller than 2 cm.

PMID- 10954453
TI  - Comparison of CT findings with resected specimens after chemoembolization with
      iodized oil for hepatocellular carcinoma.
AB  - OBJECTIVE: We assessed the role of dynamic CT in the evaluation of the efficacy
      of transarterial chemoembolization with iodized oil for hepatocellular carcinoma.
      MATERIALS AND METHODS: We examined 41 hepatocellular carcinoma lesions (mean
      diameter, 5.0 cm) in 40 patients (mean age, 60.6 years) who underwent
      transarterial injection of iodized oil alone (n = 3) or emulsion of iodized oil
      and doxorubicin hydrochloride (n = 10) followed by gelatin sponge particles (n =
      27) and subsequent hepatectomy. On dynamic CT performed within 3 weeks before
      oily transarterial chemoembolization and within 4 weeks before surgery, we
      calculated the rate of necrosis on the basis of the assumption that the portion
      that retained iodized oil represented necrosis. We also calculated the reduction
      rate of the tumor. CT findings were compared with pathologic findings of resected
      specimens. RESULTS: Pathologic specimens and the necrosis rate measured on CT
      showed a good correlation (r = 0.83) when the portion of tumor that retained
      iodized oil was considered necrosis. No correlation existed if the portion that
      retained iodized oil was considered viable. We noted no significant correlation
      (r = 0.38) between the reduction rate of the tumor and necrosis rate. Also, we
      noted no correlation (r = 0.52) between the interval between transarterial oily
      chemoembolization and surgery and the reduction rate of the tumor. CONCLUSION: CT
      is suitable for the evaluation of the efficacy of oily chemoembolization for
      hepatocellular carcinoma on the basis of the assumption that the portion of tumor
      that retains iodized oil is necrotic. The rate of tumor size reduction measured
      on CT did not correlate with the therapeutic effect of chemoembolization.

PMID- 10954454
TI  - CT versus sonography for monitoring radiofrequency ablation in a porcine liver.
AB  - OBJECTIVE: The objective of this study was to compare CT and sonography for
      monitoring radiofrequency (RF) lesions in porcine livers. SUBJECTS AND METHODS:
      RF lesions (n = 12) were created in three pig livers by applying 13 min of
      current to a multielectrode RF probe with a target temperature of 95 degrees C.
      Helical unenhanced CT and corresponding axial sonography were performed before
      ablation, at 2 min, 8 min, and immediately after ablation. Contrast-enhanced CT
      was performed after ablation. CT scans and sonograms were evaluated by blinded
      observers for conspicuity of the RF lesion, edge detection (visibility of liver
      lesion interface), and artifacts. Hounsfield units were recorded at every time
      interval, and radiologic-pathologic correlation for lesion size and configuration
      was performed. RESULTS: Mean size of RF lesions was 3. 03 +/- 0.9 cm. On CT, RF
      lesions had consistently lower attenuation values than surrounding liver (22.2 H
      lower than liver at 8 min, p < 0.0001). Echogenicity was variable with sonography
      (hypoechoic = 59%, hyperechoic = 25%, isoechoic = 16%). Unenhanced CT
      significantly improved conspicuity, edge detection of RF lesions, and decreased
      artifacts compared with sonography (p < 0.05). Contrast-enhanced CT improved RF
      lesion detection, border discrimination, and artifacts compared with sonography
      (p < 0.05). Unenhanced CT had the best correlation to pathologic size (r = 0.74),
      followed by contrast-enhanced CT (r = 0.72) and sonography (r = 0.56). Contrast
      enhanced CT best correlated with lesion shape, but slightly overestimated size
      because of areas of ischemia peripheral to the RF lesion. CONCLUSION: In this
      animal model, unenhanced CT was an effective way to monitor RF ablation compared
      with sonography because of increased lesion discrimination, reproducible
      decreased attenuation during ablation, and improved correlation to pathologic
      size.

PMID- 10954455
TI  - Evaluation of aberrant bile ducts before laparoscopic cholecystectomy: helical CT
      cholangiography versus MR cholangiography.
AB  - OBJECTIVE: The purpose of our study was to compare the accuracy of helical CT
      cholangiography and that of MR cholangiography in the diagnosis of aberrant bile
      ducts or cystic ducts before laparoscopic cholecystectomy. SUBJECTS AND METHODS:
      A total of 120 consecutive patients, including 114 patients with
      cholecystolithiasis and six with gallbladder polyps, were treated using
      laparoscopic cholecystectomy between November 1996 and August 1998. Eighteen
      (15%) of the 120 patients were suspected of having aberrant bile ducts or cystic
      ducts on helical CT cholangiography, and 16 of these 18 patients were
      subsequently examined on MR cholangiography. For the 16 patients who underwent
      both imaging examinations, findings from helical CT cholangiography and MR
      cholangiography were compared with intraoperative cholangiography. RESULTS:
      Aberrant bile ducts in 13 patients and aberrant cystic ducts in three patients
      were divided into six types on the basis of the results of intraoperative
      cholangiography. Although these types were clearly identified using helical CT
      cholangiography in all 16 patients, the anatomic variants were not correctly
      identified in seven (44%) of the 16 patients with MR cholangiography. False
      negative findings were mainly a result of the insertion sites of the cystic ducts
      or aberrant bile ducts being obscured by aberrant bile ducts or duodenum. Two
      (2%) of the 120 patients developed mild adverse reactions to the contrast
      material, but neither required treatment. CONCLUSION: Helical CT cholangiography
      clearly showed aberrant bile ducts and cystic ducts, but visualization of these
      structures on MR cholangiography was unsatisfactory because of overlapping
      duodenum and hepatic ducts.

PMID- 10954456
TI  - CT features of intraductal intrahepatic cholangiocarcinoma.
AB  - OBJECTIVE: The objective of this report was to describe the CT features of
      intraductal intrahepatic cholangiocarcinoma. CONCLUSION: Segmental or lobar
      dilatation of the intrahepatic bile ducts associated with or without intraductal
      polypoid mass, amorphous structures, or both with slight hyperattenuation are
      common CT findings of intraductal intrahepatic cholangiocarcinoma. The size of
      the intraductal mass determines the visibility on CT.

PMID- 10954457
TI  - Diagnosis of primary versus secondary achalasia: reassessment of clinical and
      radiographic criteria.
AB  - OBJECTIVE: Our purpose was to reassess the usefulness of barium studies and
      various clinical parameters for differentiating primary from secondary achalasia.
      MATERIALS AND METHODS: Radiology files from 1989 through 1999 revealed 29
      patients with primary achalasia and 10 with secondary achalasia (caused by
      carcinoma of the esophagus in three, of the gastric cardia in three, of the lung
      in three, and of the uterus in one) who met our study criteria. The radiographs
      were reviewed to determine the morphologic features of the narrowed distal
      esophageal segment and gastric cardia and fundus. Medical records were also
      reviewed to determine the clinical presentation; endoscopic, manometric, and
      surgical findings; and treatment. RESULTS: The mean patient age was 53 years in
      primary achalasia versus 69 years in secondary achalasia (p = 0.03). The mean
      duration of dysphagia was 4.5 years in primary achalasia versus 1.9 months in
      secondary achalasia (p <0.0001). The narrowed distal esophageal segment had a
      mean length of 1.9 cm in primary achalasia versus 4.4 cm in secondary achalasia
      (p < 0.0001), and the esophagus had a mean diameter of 6.2 cm in primary
      achalasia versus 4.1 cm in secondary achalasia (p <0.0001). The narrowed segment
      was eccentric or nodular or had abrupt proximal borders in only four of 10
      patients with secondary achalasia, and evidence of tumor was present in the
      gastric fundus in only three. CONCLUSION: When findings of achalasia are present
      on barium studies, a narrowed distal esophageal segment longer than 3.5 cm with
      little or no proximal dilatation in a patient with recent onset of dysphagia
      should be considered highly suggestive of secondary achalasia, even in the
      absence of other suspicious radiographic findings.

PMID- 10954458
TI  - Mesenteric and portal venous thrombosis treated by transjugular mechanical
      thrombolysis.

PMID- 10954459
TI  - Transrectal sonography of anal sphincter infiltration in lower rectal carcinoma.
AB  - OBJECTIVE: The purpose of the study was to assess the accuracy of transrectal
      sonography in determining invasion by lower rectal cancer into the anal canal.
      SUBJECTS AND METHODS: Thirty-eight patients (14 women, 24 men; mean age, 65
      years) with lower rectal cancer underwent transrectal sonography before surgery.
      Both depth of infiltration and tumor invasion into the anal canal were assessed,
      and results were compared with histopathology of the resected specimens. RESULTS:
      Infiltration into the anal canal was found histopathologically in 12 (32%) of 38
      patients. Transrectal sonography revealed a true-positive diagnosis in 11 of
      these 12 patients. A false-positive diagnosis of anal canal infiltration was made
      in two patients for a sensitivity of 91%, a specificity of 85%, and an accuracy
      of 92%. In the 11 patients diagnosed correctly on transrectal sonography, the
      depth of tumor infiltration into the anal canal corresponded with histopathology.
      CONCLUSION: This study shows that transrectal sonography is an accurate method
      for assessment of anal canal infiltration in lower rectal cancer.

PMID- 10954460
TI  - Prospective assessment of accuracy of endoanal MR imaging and endosonography in
      patients with fecal incontinence.
AB  - OBJECTIVE: Endoanal MR imaging was prospectively compared with anal
      endosonography to determine any superiority in the characterization of sphincter
      morphology in fecal incontinence. SUBJECTS AND METHODS: Fifty-two consecutive
      patients with fecal incontinence were examined with anal endosonography and
      endoanal MR imaging after a detailed bowel history, clinical examination, and
      complete anorectal physiologic testing. External and internal anal sphincter
      integrity was noted on both endosonograms and MR images by two radiologists in
      consensus, who read individual scans in a random order to avoid recall bias.
      Imaging findings were subsequently compared, and arbitration of any disagreement
      between endosonography and MR imaging was made in consensus by a surgeon and a
      gastroenterologist who also had access to the patient's history, clinical
      examination, and anorectal physiologic testing results. RESULTS: Complete
      agreement was found between anal endosonographic and MR imaging interpretations
      in 32 patients (62%): 10 with combined external and internal sphincter injuries,
      two with isolated internal sphincter injury, and 20 with intact sphincters. Of 20
      patients in whom results of the scans were disparate, incorrect interpretation
      was found on endosonography in six patients, on MR imaging in 15. Overall, one
      error relating to the internal sphincter was made on endosonography versus 12 on
      MR imaging (p = 0.002), and five errors relating to the external sphincter were
      made on endosonography versus six on MR imaging (p = 1.0). CONCLUSION: This study
      suggests that endoanal sonography and endoanal MR imaging are equivalent in
      diagnosing external anal sphincter injury, but MR imaging is inferior in
      diagnosing internal anal sphincter injury.

PMID- 10954461
TI  - Small flat umbilicated tumors of the colon: radiographic and pathologic findings.
AB  - OBJECTIVE: We describe the radiographic and pathologic findings of small flat
      umbilicated tumors of the colon detected on double-contrast barium enema
      examinations performed in a Western population. CONCLUSION: Unlike those reported
      by Japanese authors, the small flat umbilicated tumors of the colon in our
      patients were usually hyperplastic polyps, previously called "inverted
      hyperplastic polyps." Nevertheless, colonoscopy with excisional biopsy is
      warranted for such tumors detected on double-contrast barium enema examinations
      because of the small possibility that these tumors represent adenoma or even
      early adenocarcinoma.

PMID- 10954462
TI  - Small renal masses: assessment of lesion characterization and vascularity on
      dynamic contrast-enhanced MR imaging with fat suppression.
AB  - OBJECTIVE: The aim of our study was to characterize renal lesions equal to or
      smaller than 3.0 cm using dynamic contrast-enhanced MR imaging with fat
      suppression by means of quantitative analysis of signal intensity. MATERIALS AND
      METHODS: We retrospectively reviewed the MR imaging examinations of 35 patients
      (20 with renal cell carcinoma, eight with angiomyolipoma, and seven with
      complicated cysts) who were studied with spin-echo and dynamic fat-suppressed
      gradient-recalled echo MR sequences, before and after the administration of
      gadopentetate dimeglumine. Every 30 sec after contrast injection, we measured the
      lesion percentage of enhancement and the ratio of contrast (lesion-renal cortex
      signal intensity difference) to noise. RESULTS: Ten renal cell carcinomas were
      classified as hypervascular (enhancement greater than that of renal cortex) and
      10 as hypovascular. The percentage of enhancement of hypervascular carcinomas was
      similar to that of renal cortex until 150 sec and greater in the late sequences
      (180-210 sec, p < 0.01). Hypovascular carcinomas had a lower percentage of
      enhancement than hypervascular carcinomas (60-210 sec, p < 0.005).
      Angiomyolipomas, after an early enhancement peak, showed values similar to those
      of hypovascular carcinomas. Complicated cysts had very low enhancement (p <
      0.001). The baseline contrast-to-noise ratio was negative for all lesions
      (hypointensity with respect to renal cortex). After gadolinium injection, the
      contrast-to-noise ratio of hypervascular carcinomas rose, becoming positive after
      150 sec. Until 60 sec, the contrast-to-noise ratio of hypovascular carcinomas
      declined slightly, whereas that of angiomyolipomas and cysts fell sharply; then
      the three curves remained stable (60-210 sec, p < 0.05 for all matches except
      angiomyolipomas versus cysts). CONCLUSION: Quantitative analysis of signal
      intensity variations during dynamic contrast-enhanced MR imaging with fat
      suppression can be useful in the characterization of small renal lesions.

PMID- 10954463
TI  - Comparison of dynamic helical CT and dynamic MR imaging in the evaluation of
      pelvic lymph nodes in cervical carcinoma.
AB  - OBJECTIVE: This study compares dynamic helical CT with dynamic MR imaging in the
      evaluation of pelvic lymph nodes in cervical carcinoma. SUBJECTS AND METHODS:
      Women with biopsy-proven cervical carcinoma prospectively underwent dynamic
      helical CT and MR imaging before surgery. A metastatic node on CT and MR imaging
      was defined as a rounded soft-tissue structure greater than 10 mm in maximal
      axial diameter or a node with central necrosis. Imaging results were compared
      with pathology, and receiver operating characteristic curves for size and shape
      were plotted on a hemipelvis basis. Nodal density and signal intensity on CT and
      MR images, respectively, were reviewed for differences between benign and
      malignant disease. RESULTS: A total of 949 lymph nodes were found at pathology in
      76 hemipelves in 43 women, of which 69 lymph nodes (7%) in 17 hemipelves (22%)
      were metastatic. Sensitivity, specificity, positive and negative predictive
      values, and accuracy of helical CT and MR imaging in the diagnosis of lymph node
      metastasis on a hemipelvis basis was 64.7%, 96.6%, 84.6%, 90.5%, and 89.5% and
      70.6%, 89.8%, 66. 7%, 91.4%, and 85.5%, respectively. Receiver operating
      characteristic curves for helical CT and MR imaging gave cutoff values of 9 and
      12 mm in maximal axial diameter, respectively, in the prediction of metastasis.
      Central necrosis had a positive predictive value of 100% in the diagnosis of
      metastasis. Signal intensity on MR imaging and density-enhancement pattern on CT
      in patients with metastatic nodes did not differ from those in patients with
      negative nodes. CONCLUSION: Helical CT and MR imaging show similar accuracy in
      the evaluation of pelvic lymph nodes in patients with cervical carcinoma. Central
      necrosis is useful in the diagnosis of metastasis in pelvic lymph nodes in
      cervical cancer.

PMID- 10954464
TI  - Embolic agents used for uterine fibroid embolization.

PMID- 10954465
TI  - MR hysterography performed with saline injection and fluid attenuated inversion
      recovery sequences: initial experience.

PMID- 10954466
TI  - Sonographically guided transurethral laser incision of a Mullerian duct cyst for
      treatment of ejaculatory duct obstruction.

PMID- 10954467
TI  - Palpable breast masses: is there a role for percutaneous imaging-guided core
      biopsy?
AB  - OBJECTIVE: The purpose of this study was to evaluate percutaneous imaging-guided
      core biopsy in the assessment of selected palpable breast masses. MATERIALS AND
      METHODS: Of 1388 consecutive breast lesions that had percutaneous imaging-guided
      core biopsy, 155 (11%) were palpable. Palpable masses referred for percutaneous
      imaging-guided core biopsy included lesions that were small, deep, mobile,
      vaguely palpable, or multiple. Biopsy guidance was sonography in 140 lesions
      (90%) and stereotaxis in 15 (10%). Surgical correlation or minimum of 2 years
      follow-up is available in 115 palpable masses in 107 women. Medical records,
      imaging studies, and histologic findings were reviewed. RESULTS: Of 115 palpable
      breast masses, 98 (85%) were referred by surgeons to the radiology department for
      percutaneous imaging-guided core biopsy and 88 (77%) had percutaneous imaging
      guided core biopsy on the day of initial evaluation at our institution.
      Percutaneous imaging-guided core biopsy spared additional diagnostic tissue
      sampling in 79 (74%) of 107 women, including 57 women with carcinoma and 22 women
      with benign findings. Percutaneous imaging-guided core biopsy did not spare
      additional tissue sampling in 28 women (26%), including 15 women in whom surgical
      biopsy was recommended on the basis of percutaneous biopsy findings and 13 women
      with benign (n = 7) or malignant (n = 6) percutaneous biopsy findings who chose
      to undergo diagnostic surgical biopsy. CONCLUSION: Percutaneous imaging-guided
      core biopsy is useful in the evaluation of palpable breast masses that are small,
      deep, mobile, vaguely palpable, or multiple. In this study, percutaneous imaging
      guided core biopsy spared additional diagnostic tissue sampling in 74% women with
      palpable breast masses.

PMID- 10954468
TI  - Comparison of rate of development and rate of change for benign and malignant
      breast calcifications at the lumpectomy bed.
AB  - OBJECTIVE: The study purpose was to evaluate the rate of development and the rate
      of change for benign and malignant breast calcifications at the lumpectomy bed.
      MATERIALS AND METHODS: Retrospective review identified 53 new calcifications at
      the lumpectomy bed in patients with available mammograms and medical records.
      Breast Imaging Reporting and Data System (BI-RADS) categories were
      retrospectively assigned on the basis of initial prospective recommendation for
      yearly follow-up (category 2), 6-month follow-up (category 3), or biopsy
      (category 4 or 5). Outcomes were defined as benign for no recurrence at the
      lumpectomy bed on biopsy or follow-up and malignant if biopsy-proven at the
      lumpectomy bed. RESULTS: The median rate of development after lumpectomy was 23
      months (range, 2-174 months) for benign and 39 months (range, 15-112 months) for
      malignant calcifications. Fifteen (28%) of 53 calcifications were classified as
      BI-RADS category 3. Twelve (80%) of 15 were downgraded to BI-RADS category 2 at a
      median follow-up of 6.5 months (range, 6-16 months); none represented recurrent
      disease. Three (20%) of 15 were upgraded to BI-RADS category 4 at the 6-month
      follow-up, one despite stability (benign) and two for increasing pleomorphism
      (malignant). Nine (17%) of 53 calcifications were classified as BI-RADS category
      4 or 5; six (67%) of the nine were malignant and three (33%) were benign at
      biopsy. Twenty-nine (55%) of 53 calcifications were classified as BI-RADS
      category 2, none representing recurrent disease. CONCLUSION: Benign
      calcifications at the lumpectomy bed usually develop earlier than malignant
      calcifications, but the rate of development overlaps. Most calcifications
      initially placed in the probably benign category evolve quickly to more benign or
      more malignant morphology. Most calcifications heralding recurrence appear
      suspicious on first presentation.

PMID- 10954469
TI  - Metastatic lobular carcinoma of the breast: patterns of spread in the chest,
      abdomen, and pelvis on CT.
AB  - OBJECTIVE: We determined the pattern of spread of metastatic lobular carcinoma in
      the chest, abdomen, and pelvis on CT. MATERIALS AND METHODS: We identified 57
      women (age range, 30-79 years; mean age, 57 years) with metastatic lobular
      carcinoma of the breast who underwent CT of the chest, abdomen, or pelvis between
      1995 and 1998. Then two experienced oncology radiologists retrospectively
      reviewed 78 CT examinations of those patients to identify sites of metastatic
      disease and to identify complications caused by metastases. RESULTS: Metastases
      were identified in bone in 46 patients (81%), lymph nodes in 27 patients (47%),
      lung in 19 patients (33%), liver in 18 patients (32%), peritoneum in 17 patients
      (30%), colon in 15 patients (26%), pleura in 13 patients (23%), adnexa in 12
      patients (21%), stomach in nine patients (16%), retroperitoneum in nine patients
      (16%), and small bowel in six patients (11%). Eighteen patients (32%) had
      gastrointestinal tract involvement that manifested as bowel wall thickening.
      Hydronephrosis was present in six patients (11%). CONCLUSION: Although lobular
      carcinoma metastasized to common metastatic sites of infiltrating ductal
      carcinoma, lobular carcinoma frequently metastasized to unusual sites, including
      the gastrointestinal tract, peritoneum, and adnexa. Gastrointestinal tract
      involvement was as frequent as liver involvement, appearing as bowel wall
      thickening on CT. Hydronephrosis was a complication of metastatic lobular
      carcinoma.

PMID- 10954470
TI  - Advanced breast biopsy instrumentation device: percentages of lesion and
      surrounding tissue removed.
AB  - OBJECTIVE: This study reports the percentage of tissue in breast biopsy specimens
      from the lesion, and from the surrounding tissue, in 101 cases of Advanced Breast
      Biopsy Instrumentation (ABBI) biopsies. It also reports the status of the
      histologic margins for the malignant biopsies. MATERIALS AND METHODS: One hundred
      one consecutive ABBI biopsies were reviewed. The ABBI specimen radiographs were
      used to measure the area occupied by the entire specimen, the area excluding the
      lesion, and the area of the lesion alone. These areas, the length, and the width
      of all specimens were statistically analyzed using computer software. RESULTS: Of
      the 101 biopsies, histologic diagnosis was malignant in 27 and benign in 74. Of
      the 27 malignancies, four had negative margins and 23 had positive margins. Of
      the 23 with positive margins, eight were ductal carcinoma in situ (tumor within
      0.5 mm or less of the surgical margin), and 15 were not ductal carcinoma in situ
      (tumor at the surgical margin). The average specimen length was 5.51 cm and the
      average width was 1.65 cm. The average percentage of lesion tissue was 9.9%.
      CONCLUSION: An average of 90.1% of tissue removed by ABBI biopsies was from
      surrounding tissue only. Uninvolved tissue is unfortunately included because of
      the cylindric geometry of the ABBI cannula. The ABBI biopsy has a high percentage
      (85.2%) of positive margins for malignant lesions and is poor excisional tool.
      For diagnostic biopsies, core needle biopsy is preferable because a smaller
      tissue volume is resected directly from the lesion site.

PMID- 10954471
TI  - Adverse effects of increased body weight on quantitative measures of mammographic
      image quality.
AB  - OBJECTIVE: The purpose of our study was to show that compressed breast thickness
      on mammograms in overweight and obese women exceeds the thickness in normal
      weight women and that increased thickness results in image degradation. SUBJECTS
      AND METHODS: Three hundred consecutive routine mammograms were reviewed. Patients
      were categorized according to body mass index. Compression thickness, compressive
      force, kilovoltage, and milliampere-seconds were recorded. Geometric unsharpness
      and contrast degradation were calculated for each body mass index category.
      RESULTS: Body mass index categories were lean (3%), normal (36%), overweight
      (36%), and obese (25%). Body mass index was directly correlated with compressed
      thickness. In the mediolateral oblique view, the mean thickness of the obese
      category exceeded normal thickness by 18 mm (p < 0.01), corresponding to a 32%
      increase in geometric unsharpness. Mean obese thickness exceeded lean thickness
      by 33 mm (p < 0.01), corresponding to a 79% increase in unsharpness. Similar
      trends were observed for the craniocaudal view. In the mediolateral oblique
      projection, there was an increase of 1.0 kVp (p < 0.01) for obese compared with
      normal and 1.7 kVp (p < 0.01) between lean and obese, corresponding,
      respectively, to a 16% and a 25% decrease in image contrast because of scatter
      and kilovoltage changes. Milliampere-seconds increased by 47% on the mediolateral
      oblique images in the obese category compared with normal body mass index.
      CONCLUSION: An increased body mass index was associated with greater compressed
      breast thickness, resulting in increased geometric unsharpness, decreased image
      contrast, and greater potential for motion unsharpness.

PMID- 10954472
TI  - CT findings of pneumonia after lung transplantation.
AB  - OBJECTIVE: The purpose of this study was to describe the CT findings of pneumonia
      in patients who had undergone lung transplantation and to determine if specific
      imaging features existed for the different infectious organisms. MATERIALS AND
      METHODS: The authors retrospectively reviewed the medical records of 262 patients
      with transplanted lungs at two lung transplantation centers. Patients with a
      documented pneumonia and correlating abnormal findings on CT (39 patients with 45
      pneumonias) were included in the study. RESULTS. Of 45 pneumonias,
      Cytomegalovirus (n = 15), Pseudomonas (n = 7), and Aspergillus (n = 8) organisms
      were the most common single responsible infectious agents. The most common CT
      findings of pneumonia consisted of consolidation (n = 37; 82%), ground-glass
      opacification (n = 34; 76%), septal thickening (n = 33; 73%), pleural effusion (n
      = 33; 73%), and multiple (n = 25; 56%) or single (n = 2; 4%) nodules. No
      significant difference in the prevalence of findings was revealed among
      bacterial, viral, and fungal pneumonias (p >.05, chisquare test). Of 25
      pneumonias in patients with a single transplanted lung, parenchymal abnormalities
      involved both lungs in 12 (48%), only the transplanted lung in 11 (44%), and only
      the native lung in two (8%). CONCLUSION: The manifestations revealed on CT of
      bacterial, viral, and fungal pneumonia after lung transplantation are similar,
      consisting of a combination of consolidation, ground-glass opacification, septal
      thickening, pleural effusion, or multiple nodules. Therefore, these findings
      cannot be used to suggest the infectious organisms in this patient population.

PMID- 10954473
TI  - CT of bronchopericardial fistula: an unusual complication of multidrug-resistant
      tuberculosis in HIV infection.

PMID- 10954474
TI  - Quantitative diffusion measurements in focal multiple sclerosis lesions:
      correlations with appearance on TI-weighted MR images.
AB  - OBJECTIVE: Relative hypointensity on T1-weighted MR imaging has been suggested as
      a putative disability marker. The purpose of our study was to determine if there
      are quantifiable diffusion differences among focal multiple sclerosis lesions
      that appear differently on conventional T1-weighted MR images. We hypothesized
      that markedly hypointense lesions on unenhanced T1-weighted images would have
      significantly increased diffusion compared with other lesions, and enhancing
      portions of lesions would have different diffusion compared with nonenhancing
      lesions. SUBJECTS AND METHODS: Average apparent diffusion coefficient (ADC) was
      calculated for 107 lesions identified on T2-weighted images in 16 patients with
      multiple sclerosis and was compared with the ADC of normal white matter in 16 age
      and sex-matched control subjects. Seventy-five nonenhancing lesions (29
      isointense, 46 hypointense) and 32 enhancing lesions (6 isointense, 26
      hypointense) were categorized on the basis of unenhanced T1-weighted MR imaging.
      RESULTS: Hypointense and isointense nonenhancing lesions both showed
      significantly higher ADC than normal white matter (p < 0.0001). Hypointense
      nonenhancing lesions showed higher ADC values than isointense nonenhancing
      lesions (p < 0.0001). Diffusion in enhancing portions of enhancing lesions was
      decreased when compared with nonenhancing portions. CONCLUSION: Quantitative
      diffusion data from MR imaging differ among multiple sclerosis lesions that
      appear different from each other on T1-weighted images. These quantitative
      diffusion differences imply microstructural differences, which may prove useful
      in documenting irreversible disease.

PMID- 10954475
TI  - MR imaging of the salivary glands in sicca syndrome: comparison of lipid profiles
      and imaging in patients with hyperlipidemia and patients with Sjogren's syndrome.
AB  - OBJECTIVE: We correlated abnormalities on MR imaging with the plasma lipid
      profiles of patients with hyperlipidemia and symptoms of sicca syndrome. SUBJECTS
      AND METHODS: MR imaging features of the salivary glands, salivary function,
      immunologic abnormalities, and plasma lipid profiles were analyzed in 24 patients
      with hyperlipidemia and symptoms of sicca syndrome and compared with those of 50
      patients with Sjogren's syndrome. RESULTS: Swelling of the parotid gland,
      impaired salivary flow, or both were observed in 20 (83%) of 24 patients with
      hyperlipidemia and symptoms of sicca syndrome. MR imaging findings included an
      enlarged parotid gland replaced with extensive lipid infiltration, whereas
      sialography of the parotid gland revealed normal findings. Immunologic studies
      and analyses of the labial glands of the mouth revealed distinctive features in
      patients with Sjogren's syndrome. Importantly, elevated levels of plasma
      triglyceride correlated with parotid gland swelling, and increased cholesterol
      levels significantly affected salivary flow. CONCLUSION: Our findings suggest a
      distinct entity of sicca syndrome in patients with hyperlipidemia compared with
      patients with Sjogren's syndrome. Characteristic MR imaging findings of salivary
      glands in patients with hyperlipidemia included extensive lipid infiltration and
      gland enlargement.

PMID- 10954476
TI  - Ultrafast MR imaging of the normal posterior fossa in fetuses.
AB  - OBJECTIVE: The purpose of our study was to determine if a standard imaging
      protocol using ultrafast MR sequences could adequately reveal normal posterior
      fossa anatomy in fetuses and, if so, to document a template on MR imaging for
      normal posterior fossa development. MATERIALS AND METHODS: A retrospective review
      found 66 MR imaging studies of 63 fetuses, 16-39 weeks' gestation age (mean, 25
      weeks' gestation), who were referred between June 1996 and May 1999 for
      evaluation of non-central nervous system anomalies revealed on prenatal
      sonography. All fetuses had normal brains and spines on prenatal sonography. The
      standard MR imaging protocol included axial, sagittal, and coronal half-Fourier
      acquisition single-shot turbo spin echo (HASTE); sagittal and coronal two
      dimensional fast low-angle shot (FLASH); and axial turbo T1-weighted FLASH images
      through the fetal brain. Structures that we analyzed were the fourth ventricle,
      the cisterna magna, the vermis, the cerebellar hemispheres, and the brainstem.
      Using the HASTE sequences, we documented gestational age-specific signal
      intensity changes in the cerebellar hemispheres and the brainstem. RESULTS: The
      posterior fossa anatomy was sufficiently well defined to exclude abnormalities of
      the fourth ventricle and cerebellar vermis in all cases. Because of high T2
      weighting, good contrast enhancement, and good signal-to-noise ratios, HASTE
      images provided the best anatomic definition of the posterior fossa. CONCLUSION:
      Normal posterior fossa anatomy can be adequately shown on ultrafast MR images,
      which can be helpful when prenatal sonography is equivocal.

PMID- 10954478
TI  - ARRS 2000 case of the Day

PMID- 10954477
TI  - Contemporary pediatric thoracic imaging.

PMID- 10954479
TI  - Case 1. Mesenteric vein thrombosis (MVT).

PMID- 10954480
TI  - Case 2. Congenital multiple peripheral pulmonary artery stenosis (Pulmonary
      branch stenosis or supravalvular pulmonary stenosis).

PMID- 10954481
TI  - Case 3. Pulmonary arteriovenous malformation (PAVM): paradoxical embolism through
      the arteriovenous fistula can cause brain abscess and infarct.

PMID- 10954482
TI  - Case 2. Retained silicone and fibrous capsule in the right breast and retained
      fibrous capsule in the left breast after removal of implants.

PMID- 10954483
TI  - Case 1: phyllodes (Phylloides or cystosarcoma phyllodes) tumor: wide local
      excision is the preferred method of treatment

PMID- 10954484
TI  - Case 3. Altered breast: paraffin injection with development of paraffinomas.

PMID- 10954485
TI  - Case 1. Mediastinal hemangioma.

PMID- 10954486
TI  - Case 2. Vertical vein (partial anomalous pulmonary venous drainage).

PMID- 10954487
TI  - Case 3. Achalasia.

PMID- 10954488
TI  - Case 1. Localized fibrous tumor of the liver.

PMID- 10954489
TI  - Case 2. Small-bowel bezoar.

PMID- 10954490
TI  - Case 3. Lymphoma involving the distal ileum.

PMID- 10954492
TI  - Case 2. Angiomyolipoma with minimal fat content.

PMID- 10954491
TI  - Case 1. Parenchymal lymphoma.

PMID- 10954493
TI  - Case 3. Spontaneous uroepithelial hemorrhage caused by warfarin overdose.

PMID- 10954494
TI  - Case 1. Extraskeletal osteosarcoma.

PMID- 10954496
TI  - Case 2. Wernicke's encephalopathy.

PMID- 10954495
TI  - Case 1. Cavernous hemangioma of the optic chiasm.

PMID- 10954497
TI  - Case 3. Frontoethmoidal encephalocele.

PMID- 10954498
TI  - Case 2. Placental site trophoblastic tumor.

PMID- 10954499
TI  - Case 1. Thyroid hemiagenesis with adenoma.

PMID- 10954501
TI  - AJR editors: past and present

PMID- 10954500
TI  - Case 3. Corpus callosal agenesis.

PMID- 10954503
TI  - Greetings from the white house

PMID- 10954502
TI  - The American Roentgen Ray Society, 1900-2000: reflections and projections.

PMID- 10954505
TI  - Gold medal winners

PMID- 10954504
TI  - Secretary's report

PMID- 10954506
TI  - Gold medal winners

PMID- 10954507
TI  - Gold medal winners

PMID- 10954508
TI  - Gold medal winners

PMID- 10954510
TI  - Award-winning scientific exhibits

PMID- 10954509
TI  - Gold medal winners

PMID- 10954511
TI  - MR imaging of bilateral renal malacoplakia after liver transplantation.

PMID- 10954512
TI  - Duodenal diaphragm associated with long-term use of nonsteriodal antiinflammatory
      drugs: a rare cause of duodenal obstruction in an adult.

PMID- 10954513
TI  - CT detection of tracheobronchial calcification in an 18-year-old on maintenance
      warfarin sodium therapy: cause and effect?

PMID- 10954514
TI  - MR imaging of encephalopathy in adult Henoch-Shonlein purpura.

PMID- 10954515
TI  - Toddler's fracture of the fibula.

PMID- 10954516
TI  - Hydatid cyst of the temporal bone: an exceptional location.

PMID- 10954517
TI  - Endolymphatic sac tumor and von Hippel-Lindau disease: imaging features.

PMID- 10954518
TI  - Effect of the cytoplasmic domain of the simian immunodeficiency virus envelope
      protein on incorporation of heterologous envelope proteins and sensitivity to
      neutralization.
AB  - In addition to the viral envelope (Env) proteins, host cell-derived proteins have
      been reported to be present in human immunodeficiency virus and simian
      immunodeficiency virus (SIV) envelopes, and it has been postulated that they may
      play a role in infection. We investigated whether the incorporation of host cell
      proteins is affected by the structure and level of incorporation of viral Env
      proteins. To compare the cellular components incorporated into SIV particles and
      how this is influenced by the structure of the cytoplasmic domain, we compared
      SIV virions with full-length and truncated Env proteins. The levels of HLA-I and
      HLA-II molecules were found to be significantly (15- to 25-fold) higher in
      virions with full-length Env than in those with a truncated Env. Virions with a
      truncated Env were also found to be less susceptible to neutralization by
      specific antibodies against HLA-I or HLA-II proteins. We also compared the level
      of incorporation into SIV virions of a coexpressed heterologous viral
      glycoprotein, the influenza virus hemagglutinin (HA) protein. We found that SIV
      infection of cells expressing influenza virus HA resulted in the production of
      phenotypically mixed SIV virions containing influenza virus HA as well as SIV
      envelope proteins. The HA proteins were more effectively incorporated into
      virions with full-length Env than in virions with truncated Env. The
      phenotypically mixed particles with full-length Env, containing higher levels of
      HA, were sensitive to neutralization with anti-HA antibody, whereas virions with
      truncated Env proteins and containing lower levels of HA were more resistant to
      neutralization by anti-HA antibody. In contrast, SIV virions with truncated Env
      proteins were found to be highly sensitive to neutralization by antisera to SIV,
      whereas virions with full-length Env proteins were relatively resistant to
      neutralization. These results indicate that the cytoplasmic domain of SIV Env
      affects the incorporation of cellular as well as heterologous viral membrane
      proteins into the SIV envelope and may be an important determinant of the
      sensitivity of the virus to neutralizing antibodies.

PMID- 10954519
TI  - Expression of mouse mammary tumor virus superantigen accelerates tumorigenicity
      of myeloma cells.
AB  - To investigate whether superantigen (SAG) from endogenous mouse mammary tumor
      virus functions as an immunogenic or a tumorigenic factor in tumor development,
      the BALB/c myeloma cell line FO was transfected with the SAG gene from the 3' Mtv
      50 long terminal repeat (LTR) open reading frame (ORF), the product of which was
      specific for Vbeta6. All five transfectants expressing Mtv-50 LTR ORF mRNA showed
      stimulatory activity for Vbeta6 T-cell hybridomas in vitro; this activity was
      inhibited by the addition of anti-Mtv-7 monoclonal antibody (MAb) or anti-major
      histocompatibility complex class II I-A(d) and I-E(d) MAb. All transfectants with
      the SAG gene grew more rapidly than did mock transfectants in BALB/c mice after
      subcutaneous inoculation, whereas all clones, including mock transfectants, grew
      equally well in athymic nude mice. A significant fraction of Vbeta6 T cells
      selectively expressed activation markers, including CD44(high), CD62L(low), and
      CD69(high), and produced large amounts of interleukin 5 (IL-5) and IL-6 in BALB/c
      mice inoculated with transfectants. These results suggested that the expression
      of viral SAG enhances the tumorigenicity of a myeloma cell line through the
      stimulation of SAG-reactive T cells.

PMID- 10954520
TI  - Bovine respiratory syncytial virus nonstructural proteins NS1 and NS2
      cooperatively antagonize alpha/beta interferon-induced antiviral response.
AB  - The functions of bovine respiratory syncytial virus (BRSV) nonstructural proteins
      NS1 and NS2 were studied by generation and analysis of recombinant BRSV carrying
      single and double gene deletions. Whereas in MDBK cells the lack of either or
      both NS genes resulted in a 5,000- to 10,000-fold reduction of virus titers, in
      Vero cells a moderate (10-fold) reduction was observed. Interestingly, cell
      culture supernatants from infected MDBK cells were able to restrain the growth of
      NS deletion mutants in Vero cells, suggesting the involvement of NS proteins in
      escape from cytokine-mediated host cell responses. The responsible factors in
      MDBK supernatants were identified as type I interferons by neutralization of the
      inhibitory effect with antibodies blocking the alpha interferon (IFN-alpha)
      receptor. Treatment of cells with recombinant universal IFN-alpha A/D or IFN-beta
      revealed severe inhibition of single and double deletion mutants, whereas growth
      of full-length BRSV was not greatly affected. Surprisingly, all NS deletion
      mutants were equally repressed, indicating an obligatory cooperation of NS1 and
      NS2 in antagonizing IFN-mediated antiviral mechanisms. To verify this finding, we
      generated recombinant rabies virus (rRV) expressing either NS1 or NS2 and
      determined their IFN sensitivity. In cells coinfected with NS1- and NS2
      expressing rRVs, virus replication was resistant to doses of IFN which caused a
      1,000-fold reduction of replication in cells infected with wild-type RV or with
      each of the NS-expressing rRVs alone. Thus, BRSV NS proteins have the potential
      to cooperatively protect an unrelated virus from IFN-alpha/beta mediated
      antiviral responses. Interestingly, BRSV NS proteins provided a more pronounced
      resistance to IFN in the bovine cell line MDBK than in cell lines of other
      origins, suggesting adaptation to host-specific antiviral responses. The findings
      described have a major impact on the design of live recombinant BRSV and HRSV
      vaccines.

PMID- 10954521
TI  - Evolution of swine H3N2 influenza viruses in the United States.
AB  - During 1998, severe outbreaks of influenza were observed in four swine herds in
      the United States. This event was unique because the causative agents, H3N2
      influenza viruses, are infrequently isolated from swine in North America. Two
      antigenically distinct reassortant viruses (H3N2) were isolated from infected
      animals: a double-reassortant virus containing genes similar to those of human
      and swine viruses, and a triple-reassortant virus containing genes similar to
      those of human, swine, and avian influenza viruses (N. N. Zhou, D. A. Senne, J.
      S. Landgraf, S. L. Swenson, G. Erickson, K. Rossow, L. Liu, K.-J. Yoon, S.
      Krauss, and R. G. Webster, J. Virol. 73:8851-8856, 1999). Because the U.S. pig
      population was essentially naive in regard to H3N2 viruses, it was important to
      determine the extent of viral spread. Hemagglutination inhibition (HI) assays of
      4, 382 serum samples from swine in 23 states indicated that 28.3% of these
      animals had been exposed to classical swine-like H1N1 viruses and 20.5% had been
      exposed to the triple-reassortant-like H3N2 viruses. The HI data suggested that
      viruses antigenically related to the double-reassortant H3N2 virus have not
      become widespread in the U.S. swine population. The seroreactivity levels in
      swine serum samples and the nucleotide sequences of six additional 1999 isolates,
      all of which were of the triple-reassortant genotype, suggested that H3N2 viruses
      containing avian PA and PB2 genes had spread throughout much of the country.
      These avian-like genes cluster with genes from North American avian viruses. The
      worldwide predominance of swine viruses containing an avian-like internal gene
      component suggests that these genes may confer a selective advantage in pigs.
      Analysis of the 1999 swine H3N2 isolates showed that the internal gene complex of
      the triple-reassortant viruses was associated with three recent phylogenetically
      distinct human-like hemagglutinin (HA) molecules. Acquisition of HA genes from
      the human virus reservoir will significantly affect the efficacy of the current
      swine H3N2 vaccines. This finding supports continued surveillance of U.S. swine
      populations for influenza virus activity.

PMID- 10954523
TI  - Intercellular transfer of a soluble viral superantigen.
AB  - Mouse mammary tumor virus (MMTV) superantigens (vSAgs) can undergo intercellular
      transfer in vivo and in vitro such that a vSAg can be presented to T cells by
      major histocompatibility complex (MHC) class II proteins on antigen-presenting
      cells (APCs) that do not express the superantigen. This process may allow T-cell
      activation to occur prior to viral infection. Consistent with these findings,
      vSAg produced by Chinese hamster ovary (CHO) cells was readily transferred to
      class II IE and IA (H-2(k) and H-2(d)) proteins on a B-cell lymphoma or mouse
      splenocytes. Fixed class II-expressing acceptor cells were used to demonstrate
      that the vSAg, but not the class II proteins, underwent intercellular transfer,
      indicating that vSAg binding to class II MHC could occur directly at the cell
      surface. Intercellular transfer also occurred efficiently to splenocytes from
      endogenous retrovirus-free mice, indicating that other proviral proteins were not
      involved. Presentation of vSAg7 produced by a class II-negative, furin protease
      deficient CHO variant (FD11) was unsuccessful, indicating that proteolytic
      processing was a requisite event and that proteolytic activity could not be
      provided by an endoprotease on the acceptor APC. Furthermore, vSAg presentation
      was effected using cell-free supernatant from class II-negative, vSAg-positive
      cells, indicating that a soluble molecule, most likely produced by proteolytic
      processing, was sufficient to stimulate T cells. Because the membrane-proximal
      endoproteolytic cleavage site in the vSAg (residues 68 to 71) was not necessary
      for intercellular transfer, the data support the notion that the carboxy-terminal
      endoproteolytic cleavage product is an active vSAg moiety.

PMID- 10954522
TI  - Human immunodeficiency virus type 1 Vif protein is an integral component of an
      mRNP complex of viral RNA and could be involved in the viral RNA folding and
      packaging process.
AB  - Virion infectivity factor (Vif) is a protein encoded by human immunodeficiency
      virus types 1 and 2 (HIV-1 and -2) and simian immunodeficiency virus, plus other
      lentiviruses, and is essential for viral replication either in vivo or in culture
      for nonpermissive cells such as peripheral blood lymphoid cells, macrophages, and
      H9 T cells. Defects in the vif gene affect virion morphology and reverse
      transcription but not the expression of viral components. It has been shown that
      Vif colocalizes with Gag in cells and Vif binds to the NCp7 domain of Gag in
      vitro. However, it seems that Vif is not specifically packaged into virions. The
      molecular mechanism(s) for Vif remains unknown. In this report, we demonstrate
      that HIV-1 Vif is an RNA-binding protein and specifically binds to HIV-1 genomic
      RNA in vitro. Further, Vif binds to HIV-1 RNA in the cytoplasm of virus-producing
      cells to form a 40S mRNP complex. Coimmunoprecipitation and in vivo UV cross
      linking assays indicated that Vif directly interact with HIV-1 RNA in the virus
      producing cells. Vif-RNA binding could be displaced by Gag-RNA binding,
      suggesting that Vif protein in the mRNP complex may mediate viral RNA interaction
      with HIV-1 Gag precursors. Furthermore, we have demonstrated that these Vif
      mutants that lose the RNA binding activity in vitro do not support vif-deficient
      HIV-1 replication in H9 T cells, suggesting that the RNA binding capacity of Vif
      is important for its function. Further studies regarding Vif-RNA interaction in
      virus-producing cells will be important for studying the function of Vif in the
      HIV-1 life cycle.

PMID- 10954524
TI  - Identification of a minimal size requirement for termination of vesicular
      stomatitis virus mRNA: implications for the mechanism of transcription.
AB  - The nonsegmented negative-strand RNA (NNS) viruses have a single-stranded RNA
      genome tightly encapsidated by the viral nucleocapsid protein. The viral
      polymerase transcribes the genome responding to specific gene-start and gene-end
      sequences to yield a series of discrete monocistronic mRNAs. These mRNAs are not
      produced in equimolar amounts; rather, their abundance reflects the position of
      the gene with respect to the single 3'-proximal polymerase entry site. Promoter
      proximal genes are transcribed in greater abundance than more distal genes due to
      a localized transcriptional attenuation at each gene junction. In recent years,
      the application of reverse genetics to the NNS viruses has allowed an examination
      of the role of the gene-start and gene-end sequences in regulating mRNA
      synthesis. These studies have defined specific sequences required for initiation,
      5' modification, termination, and polyadenylation of the viral mRNAs. In the
      present report, working with Vesicular stomatitis virus, the prototypic
      Rhabdovirus, we demonstrate that a gene-end sequence must be positioned a minimal
      distance from a gene-start sequence for the polymerase to efficiently terminate
      transcription. Gene-end sequences were almost completely ignored in
      transcriptional units less than 51 nucleotides. Transcriptional units of 51 to 64
      nucleotides allowed termination at the gene-end sequence, although the frequency
      with which polymerase failed to terminate and instead read through the gene-end
      sequence to generate a bicistronic transcript was enhanced compared to the
      observed 1 to 3% for wild-type viral mRNAs. In all instances, failure to
      terminate at the gene end prevented initiation at the downstream gene start site.
      In contrast to this size requirement, we show that the sequence between the gene
      start and gene-end signals, or its potential to adopt an RNA secondary structure,
      had only a minor effect on the efficiency with which polymerase terminated
      transcription. We suggest three possible explanations for the failure of
      polymerase to terminate transcription in response to a gene-end sequence
      positioned close to a gene-start sequence which contribute to our emerging
      picture of the mechanism of transcriptional regulation in this group of viruses.

PMID- 10954525
TI  - In vivo genomic footprinting of the human T-cell leukemia virus type 1 (HTLV-1)
      long terminal repeat enhancer sequences in HTLV-1-infected human T-cell lines
      with different levels of Tax I activity.
AB  - The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) enhances viral
      gene expression through sequences in the U3 region of the viral long terminal
      repeat. These sequences consist of three imperfect 21-bp repeats (TRE-1s) and a
      region between the promoter-central and promoter-proximal 21-bp repeats (TRE-2).
      The TRE-1s contain a core cyclic AMP response element (CRE) motif and can be
      bound by CREB, ATF-1, ATF-2, and other members of the CREB-ATF superfamily of
      transcription factors. Tax enhances CREB binding to TRE-1 in vitro, and it
      promotes dimerization of CREB as well as other bZIP proteins. Using ligation
      mediated PCR on in vivo dimethyl sulfate-treated HTLV-1-infected cell lines MT-2
      and MT-4, we have compiled a profile of protein occupancy in the HTLV-1 enhancer
      sequences in the presence of high (MT-2) and low (MT-4) levels of biologically
      active Tax I. The in vivo footprinting showed that all three TRE-1s were bound by
      protein(s), but only in MT-2 cells. In MT-2 cells, all TRE-1s showed strong
      protection of the G residues in the central CRE, and the footprints extended to
      differing degrees into the GC-rich flanking sequences. This indicated Tax I
      dependent loading of transcription factors onto the HTLV-1 TRE-1s in vivo. In
      vivo footprinting on TRE-2 indicated that this region was bound by proteins
      regardless of the Tax I status of the cell line. However, the presence of Tax I
      increased the extent and altered the profile of proteins binding TRE-2 in vivo.

PMID- 10954526
TI  - Direct ex vivo kinetic and phenotypic analyses of CD8(+) T-cell responses induced
      by DNA immunization.
AB  - CD8(+) T-cell responses can be induced by DNA immunization, but little is known
      about the kinetics of these responses in vivo in the absence of restimulation or
      how soon protective immunity is conferred by a DNA vaccine. It is also unclear if
      CD8(+) T cells primed by DNA vaccines express the vigorous effector functions
      characteristic of cells primed by natural infection or by immunization with a
      recombinant live virus vaccine. To address these issues, we have used the
      sensitive technique of intracellular cytokine staining to carry out direct ex
      vivo kinetic and phenotypic analyses of antigen-specific CD8(+) T cells present
      in the spleens of mice at various times after (i) a single intramuscular
      administration of a plasmid expressing the nucleoprotein (NP) gene from
      lymphocytic choriomeningitis virus (LCMV), (ii) infection by a recombinant
      vaccinia virus carrying the same protein (vvNP), or (iii) LCMV infection. In
      addition, we have evaluated the rapidity with which protective immunity against
      both lethal and sublethal LCMV infections is achieved following DNA vaccination.
      The CD8(+) T-cell response in DNA-vaccinated mice was slightly delayed compared
      to LCMV or vvNP vaccinees, peaking at 15 days postimmunization. Interestingly,
      the percentage of antigen-specific CD8(+) T cells present in the spleen at day 15
      and later time points was similar to that observed following vvNP infection. T
      cells primed by DNA vaccination or by infection exhibited similar cytokine
      expression profiles and had similar avidities for an immunodominant cytotoxic T
      lymphocyte epitope peptide, implying that the responses induced by DNA
      vaccination differ quantitatively but not qualitatively from those induced by
      live virus infection. Surprisingly, protection from both lethal and sublethal
      LCMV infections was conferred within 1 week of DNA vaccination, well before the
      peak of the CD8(+) T-cell response.

PMID- 10954527
TI  - Avian retrovirus DNA internal attachment site requirements for full-site
      integration in vitro.
AB  - Concerted integration of retrovirus DNA termini into the host chromosome in vivo
      requires specific interactions between the cis-acting attachment (att) sites at
      the viral termini and the viral integrase (IN) in trans. In this study,
      reconstruction experiments with purified avian myeloblastosis virus (AMV) IN and
      retrovirus-like donor substrates containing wild-type and mutant termini were
      performed to map the internal att DNA sequence requirements for concerted
      integration, here termed full-site integration. The avian retrovirus mutations
      were modeled after internal att site mutations studied at the in vivo level with
      human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV).
      Systematic overlapping 4-bp deletions starting at nucleotide positions 7, 8, and
      9 in the U3 terminus had a decreasing detrimental gradient effect on full-site
      integration, while more internal 4-bp deletions had little or no effect. This
      decreasing detrimental gradient effect was measured by the ability of mutant U3
      ends to interact with wild-type U3 ends for full-site integration in trans.
      Modification of the highly conserved C at position 7 on the catalytic strand to
      either A or T resulted in the same severe decrease in full-site integration as
      the 4-bp deletion starting at this position. These studies suggest that
      nucleotide position 7 is crucial for interactions near the active site of IN for
      integration activity and for communication in trans between ends bound by IN for
      full-site integration. The ability of AMV IN to interact with internal att
      sequences to mediate full-site integration in vitro is similar to the internal
      att site requirements observed with MLV and HIV-1 in vivo and with their
      preintegration complexes in vitro.

PMID- 10954528
TI  - gammadelta(+) T-Lp6phocyte cytotoxicity against envelope-expressing target cells
      is unique to the alymphocytic state of bovine leukemia virus infection in the
      natural host.
AB  - Bovine leukemia virus (BLV) is a complex B-lymphotrophic retrovirus of cattle and
      the causative agent of enzootic bovine leukosis. Serum antibody in infected
      animals does not correlate with protection from disease, yet only some animals
      develop severe disease. While a cytotoxic T-lymphocyte response may be
      responsible for directing BLV pathogenesis, this possibility has been left
      largely unexplored, in part since the lack of readily established cytotoxic
      target cells in cattle has hampered such studies. Using long-term naturally
      infected alymphocytic (AL) cattle, we have established the existence of cytotoxic
      T-lymphocyte response against BLV envelope proteins (Env; gp51/gp30). In vitro
      expanded peripheral blood mononuclear (PBM) cell effector populations consisted
      mainly of gammadelta(+) (>40%), CD4(+) (>35%), and CD8(+) (>10%) T lymphocytes.
      Specific lysis of autologous fibroblasts infected with recombinant vaccinia virus
      (rVV) delivering the BLV env gene ranged from 30 to 65%. Depletion studies
      indicated that gammadelta(+) and not CD8(+) T cells were responsible for the
      cytotoxicity against autologous rVVenv-expressing fibroblasts. Additionally,
      cultured effector cells lysed rVVenv-expressing autologous fibroblasts and rVVenv
      expressing xenogeneic targets similarly, suggesting a lack of genetic restricted
      killing. Restimulation of effector populations increased the proportion of
      gammadelta(+) T cells and concomitantly Env-specific cytolysis. Interestingly,
      culture of cells from BLV-negative or persistently lymphocytic cattle failed to
      elicit such cytotoxic responses or increase in gammadelta(+) T-cell numbers.
      These results imply that cytotoxic gammadelta(+) T lymphocytes from only AL
      cattle recognize BLV Env without a requirement for classical major
      histocompatibility complex interactions. It is known that gammadelta(+) T
      lymphocytes are diverse and numerous in cattle, and here we show that they may
      serve a surveillance role during natural BLV infection.

PMID- 10954529
TI  - Development of minimal lentivirus vectors derived from simian immunodeficiency
      virus (SIVmac251) and their use for gene transfer into human dendritic cells.
AB  - Lentivirus-derived vectors are very promising gene delivery systems since they
      are able to transduce nonproliferating differentiated cells, while murine
      leukemia virus-based vectors can only transduce cycling cells. Here we report the
      construction and characterization of highly efficient minimal vectors derived
      from simian immunodeficiency virus (SIVmac251). High-fidelity PCR amplification
      of DNA fragments was used to generate a minimal SIV vector formed from a 5'
      cytomegalovirus early promoter, the 5' viral sequences up to the 5' end of gag
      required for reverse transcription and packaging, the Rev-responsive element, a
      gene-expressing cassette, and the 3' long terminal repeat (LTR). Production of
      SIV vector particles was achieved by transfecting 293T cells with the vector DNA
      and helper constructs coding for the viral genes and the vesicular stomatitis
      virus glycoprotein G envelope. These SIV vectors were found to have transducing
      titers reaching 10(7) transducing units/ml on HeLa cells and to deliver a gene
      without transfer of helper functions to target cells. The central polypurine
      tract can be included in the minimal vector, resulting in a two- to threefold
      increase in the transduction titers on dividing or growth-arrested cells. Based
      on this minimal SIV vector, a sin vector was designed by deleting 151 nucleotides
      in the 3' LTR U3 region, and this SIV sin vector retained high transduction
      titers. Furthermore, the minimal SIV vector was efficient at transducing
      terminally differentiated human CD34(+) cell-derived or monocyte-derived
      dendritic cells (DCs). Results show that up to 40% of human primary DCs can be
      transduced by the SIV vectors. This opens a new perspective in the field of
      immunotherapy.

PMID- 10954530
TI  - Response of foot-and-mouth disease virus to increased mutagenesis: influence of
      viral load and fitness in loss of infectivity.
AB  - Passage of foot-and-mouth disease virus (FMDV) in cell culture in the presence of
      the mutagenic base analog 5-fluorouracil or 5-azacytidine resulted in decreases
      of infectivity and occasional extinction of the virus. Low viral loads and low
      viral fitness enhanced the frequency of extinction events; this finding was shown
      with a number of closely related FMDV clones and populations differing by up to
      10(6)-fold in relative fitness in infections involving either single or multiple
      passages in the absence or presence of the chemical mutagens. The mutagenic
      treatments resulted in increases of 2- to 6.4-fold in mutation frequency and up
      to 3-fold in mutant spectrum complexity. The largest increase observed
      corresponded to the 3D (polymerase)-coding region, which is highly conserved in
      nonmutagenized FMDV populations. As a result, nucleotide sequence heterogeneity
      for the 3D-coding region became very similar to that for the variable VP1-coding
      region in FMDVs multiply passaged in the presence of chemical mutagens. The
      results suggest that strategies to combine reductions of viral load and viral
      fitness could be effectively associated with extinction mutagenesis as a
      potential new antiviral strategy.

PMID- 10954531
TI  - Sequences in the 5' and 3' R elements of human immunodeficiency virus type 1
      critical for efficient reverse transcription.
AB  - The genome of human immunodeficiency virus type 1 (HIV-1) contains two direct
      repeats (R) of 97 nucleotides at each end. These elements are of critical
      importance during the first-strand transfer of reverse transcription, during
      which the minus-strand strong-stop DNA (-sssDNA) is transferred from the 5' end
      to the 3' end of the genomic RNA. This transfer is critical for the synthesis of
      the full-length minus-strand cDNA. These repeats also contain a variety of other
      functional domains involved in many aspects of the viral life cycle. In this
      study, we have introduced a series of mutations into the 5', the 3', or both R
      sequences designed to avoid these other functional domains. Using a single-round
      infectivity assay, we determined the ability of these mutants to undergo the
      various steps of reverse transcription utilizing a semiquantitative PCR analysis.
      We find that mutations within the first 10 nucleotides of either the 5' or the 3'
      R sequence resulted in virions that were markedly defective for reverse
      transcription in infected cells. These mutations potentially introduce mismatches
      between the full-length -sssDNA and 3' acceptor R. Even mutations that would
      create relatively small mismatches, as little as 3 bp, resulted in inefficient
      reverse transcription. In contrast, virions containing identically mutated R
      elements were not defective for reverse transcription or infectivity. Using an
      endogenous reverse transcription assay with disrupted virus, we show that virions
      harboring the 5' or the 3' R mutations were not intrinsically defective for DNA
      synthesis. Similarly sized mismatches slightly further downstream in either the
      5', the 3', or both R sequences were not detrimental to continued reverse
      transcription in infected cells. These data are consistent with the idea that
      certain mismatches within 10 nucleotides downstream of the U3-R junction in HIV-1
      cause defects in the stability of the cDNA before or during the first-strand
      transfer of reverse transcription leading to the rapid disappearance of the 
      sssDNA in infected cells. These data also suggest that the great majority of
      first-strand transfers in HIV-1 occur after the copying of virtually the entire
      5' R.

PMID- 10954533
TI  - Lack of functional receptors is the only barrier that prevents caprine arthritis
      encephalitis virus from infecting human cells.
AB  - Barriers to replication of viruses in potential host cells may occur at several
      levels. Lack of suitable and functional receptors on the host cell surface,
      thereby precluding entry of the virus, is a frequent reason for noninfectivity,
      as long as no alternative way of entry (e.g., pinocytosis, antibody-dependent
      adsorption) can be exploited by the virus. Other barriers can intervene at later
      stages of the virus life cycle, with restrictions on transcription of the viral
      genome, incorrect translation and posttranslational processing of viral proteins,
      inefficient viral assembly, and release or efficient early induction of apoptosis
      in the infected cell. The data we present here demonstrate that replication of
      caprine arthritis-encephalitis virus (CAEV) is restricted in a variety of human
      cell lines and primary tissue cultures. This barrier was efficiently overcome by
      transfection of a novel infectious complete-proviral CAEV construct into the same
      cells. The successful infection of human cells with a vesicular stomatitis virus
      (VSV) G-pseudotyped Env-defective CAEV confirmed that viral entry is the major
      obstacle to CAEV infection of human cells. The fully efficient productive
      infection obtained with the VSV-G-protein-pseudotyped infectious CAEV
      strengthened the evidence that lack of viral entry is the only practical barrier
      to CAEV replication in human cells. The virus thus produced retained its original
      host cell specificity and acquired no propensity to propagate further in human
      cultures.

PMID- 10954532
TI  - Inherent instability of poliovirus genomes containing two internal ribosome entry
      site (IRES) elements supports a role for the IRES in encapsidation.
AB  - Previous studies have described poliovirus genomes in which the internal ribosome
      entry (IRES) for encephalomyocarditis virus (EMCV) is positioned between the P1
      and P2-P3 open reading frames of the poliovirus genome. Although these
      dicistronic poliovirus genomes were replication competent, most exhibited
      evidence of genetic instability, and the EMCV IRES was deleted upon serial
      passage. One possible reason for instability of the genome is that the
      dicistronic genome was at least 108% larger than the wild-type poliovirus genome,
      which could reduce the efficiency of encapsidation. To address this possibility,
      we have constructed dicistronic poliovirus replicons by substituting the EMCV
      IRES and the gene encoding luciferase in place of the poliovirus P1 region; the
      resulting dicistronic replicons are smaller than the wild-type poliovirus genome.
      One dicistronic genome was constructed in which the poliovirus 5' nontranslated
      region was fused to the gene encoding luciferase, followed by the complete EMCV
      IRES fused to the P2-P3 region of the poliovirus genome (PV-Luc-EMCV). A second
      dicistronic genome, EMCV-Luc-PV, was constructed with the first 108 nucleotides
      of the poliovirus genome fused to the EMCV IRES, followed by the gene encoding
      luciferase and the poliovirus IRES fused to the remaining P2-P3 region of the
      poliovirus genome. Both dicistronic replicons expressed abundant luciferase
      following transfection of in vitro-transcribed RNA into HeLa cells at 30, 33, or
      37 degrees C. The luciferase activity detected from PV-Luc-EMCV increased rapidly
      during the first 4 h following transfection and then plateaued, peaking after
      approximately 24 h. In contrast, the luciferase activity detected from EMCV-Luc
      PV increased for approximately 12 h following transfection; by 24 h
      posttransfection, the overall levels of luciferase activity were similar to that
      of PV-Luc-EMCV. To analyze encapsidation of the dicistronic replicons, we used a
      system in which the capsid protein (P1) is provided in trans from a recombinant
      vaccinia virus (VV-P1). The PV-Luc-EMCV replicon was unstable upon serial passage
      in the presence of VV-P1, with deletions of the EMCV IRES region detected even
      during the initial transfection at 37 degrees C. Following serial passage in the
      presence of VV-P1 at 33 or 30 degrees C, we detected deleted genomes in which the
      luciferase gene was fused with the P2-P3 genes of the poliovirus genome so as to
      maintain the translational reading frame. In contrast, the EMCV-Luc-PV replicon
      was genetically stable during passage with VV-P1 at 33 or 30 degrees C. The
      encapsidation of EMCV-Luc-PV was compared to that of monocistronic replicons
      encoding luciferase with either a poliovirus or EMCV IRES. Analysis of the
      encapsidated replicons after four serial passages with VV-P1 revealed that the
      dicistronic replicon was encapsidated more efficiently than the monocistronic
      replicon with the EMCV IRES but less efficiently than the monicistronic replicon
      with the poliovirus IRES. The results of this study suggest a genetic
      predisposition for picornavirus genomes to contain a single IRES region and are
      discussed with respect to a role of the IRES in encapsidation.

PMID- 10954534
TI  - CD28 costimulatory blockade exacerbates disease severity and accelerates epitope
      spreading in a virus-induced autoimmune disease.
AB  - Theiler's murine encephalomyelitis virus (TMEV) is a natural mouse pathogen which
      causes a lifelong persistent infection of the central nervous system (CNS)
      accompanied by T-cell-mediated myelin destruction leading to chronic, progressive
      hind limb paralysis. TMEV-induced demyelinating disease (TMEV-IDD) is considered
      to be a highly relevant animal model for the human autoimmune disease multiple
      sclerosis (MS), which is thought to be initiated as a secondary consequence of a
      virus infection. Although TMEV-IDD is initiated by virus-specific CD4(+) T cells
      targeting CNS-persistent virus, CD4(+) T-cell responses against self myelin
      protein epitopes activated via epitope spreading contribute to chronic disease
      pathogenesis. We thus examined the ability of antibodies directed against B7
      costimulatory molecules to regulate this chronic virus-induced immunopathologic
      process. Contrary to previous studies showing that blockade of B7-CD28
      costimulatory interactions inhibit the initiation of experimental autoimmune
      encephalomyelitis, treatment of SJL mice at the time of TMEV infection with
      murine CTLA-4 immunoglobulin or a combination of anti-B7-1 and anti-B7-2
      antibodies significantly enhanced clinical disease severity. Costimulatory
      blockade inhibited early TMEV-specific T-cell and antibody responses critical in
      clearing peripheral virus infection. The inhibition of virus-specific immune
      responses led to significantly increased CNS viral titers resulting in increased
      damage to myelin-producing oligodendrocytes. Following clearance of the
      costimulatory antagonists, epitope spreading to myelin epitopes was accelerated
      as a result of the increased availability of myelin epitopes leading to a more
      severe chronic disease course. Our results raise concern about the potential use
      of B7-CD28 costimulatory blockade to treat human autoimmune diseases potentially
      associated with acute or persistent virus infections.

PMID- 10954535
TI  - Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20
      is modulated by coreceptor specificity defined by the V3 loop of gp120.
AB  - T-20 is a synthetic peptide that potently inhibits replication of human
      immunodeficiency virus type 1 by interfering with the transition of the
      transmembrane protein, gp41, to a fusion active state following interactions of
      the surface glycoprotein, gp120, with CD4 and coreceptor molecules displayed on
      the target cell surface. Although T-20 is postulated to interact with an N
      terminal heptad repeat within gp41 in a trans-dominant manner, we show here that
      sensitivity to T-20 is strongly influenced by coreceptor specificity. When 14 T
      20-naive primary isolates were analyzed for sensitivity to T-20, the mean 50%
      inhibitory concentration (IC(50)) for isolates that utilize CCR5 for entry (R5
      viruses) was 0.8 log(10) higher than the mean IC(50) for CXCR4 (X4) isolates (P =
      0. 0055). Using NL4.3-based envelope chimeras that contain combinations of
      envelope sequences derived from R5 and X4 viruses, we found that determinants of
      coreceptor specificity contained within the gp120 V3 loop modulate this
      sensitivity to T-20. The IC(50) for all chimeric envelope viruses containing R5
      V3 sequences was 0.6 to 0.8 log(10) higher than that for viruses containing X4 V3
      sequences. In addition, we confirmed that the N-terminal heptad repeat of gp41
      determines the baseline sensitivity to T-20 and that the IC(50) for viruses
      containing GIV at amino acid residues 36 to 38 was 1.0 log(10) lower than the
      IC(50) for viruses containing a G-to-D substitution. The results of this study
      show that gp120-coreceptor interactions and the gp41 N-terminal heptad repeat
      independently contribute to sensitivity to T-20. These results have important
      implications for the therapeutic uses of T-20 as well as for unraveling the
      complex mechanisms of virus fusion and entry.

PMID- 10954536
TI  - The infectivities of turnip yellow mosaic virus genomes with altered tRNA mimicry
      are not dependent on compensating mutations in the viral replication protein.
AB  - Five highly infectious turnip yellow mosaic virus (TYMV) genomes with sequence
      changes in their 3'-terminal regions that result in altered aminoacylation and
      eEF1A binding have been studied. These genomes were derived from cloned parental
      RNAs of low infectivity by sequential passaging in plants. Three of these genomes
      that are incapable of aminoacylation have been reported previously (J. B.
      Goodwin, J. M. Skuzeski, and T. W. Dreher, Virology 230:113-124, 1997). We now
      demonstrate by subcloning the 3' untranslated regions into wild-type TYMV RNA
      that the high infectivities and replication rates of these genomes compared to
      their progenitors are mostly due to a small number of mutations acquired in the
      3' tRNA-like structure during passaging. Mutations in other parts of the genome,
      including the replication protein coding region, are not required for high
      infectivity but probably do play a role in optimizing viral amplification and
      spread in plants. Two other TYMV RNA variants of suboptimal infectivities, one
      that accepts methionine instead of the usual valine and one that interacts less
      tightly with eEF1A, were sequentially passaged to produce highly infectious
      genomes. The improved infectivities of these RNAs were not associated with
      increased replication in protoplasts, and no mutations were acquired in their 3'
      tRNA-like structures. Complete sequencing of one genome identified two mutations
      that result in amino acid changes in the movement protein gene, suggesting that
      improved infectivity may be a function of improved viral dissemination in plants.
      Our results show that the wild-type TYMV replication proteins are able to amplify
      genomes with 3' termini of variable sequence and tRNA mimicry. These and previous
      results have led to a model in which the binding of eEF1A to the 3' end to
      antagonize minus-strand initiation is a major role of the tRNA-like structure.

PMID- 10954537
TI  - Specific ablation of antiviral gene expression in macrophages by antibody
      dependent enhancement of Ross River virus infection.
AB  - Ross River virus (RRV) is an indigenous Australian arthropod-borne alphavirus
      responsible for epidemic polyarthritis (EPA), myalgia, and lethargy in humans.
      Macrophages and monocytes have been associated with human RRV disease, and
      previous studies have shown that RRV is capable of infecting macrophages via both
      a natural virus receptor and by Fc receptor-mediated antibody-dependent
      enhancement (ADE). Similar to other viruses, such as human immunodeficiency virus
      and dengue virus, ADE infection results in dramatic RRV growth increases for in
      vitro macrophage cultures. This study demonstrates that RRV could resist
      lipopolysaccharide (LPS)-induced antiviral activity in macrophage cultures when
      infection was via the ADE pathway. Investigation of this infection pathway found
      that RRV was able to suppress the transcription and translation of key antiviral
      genes (tumor necrosis factor and inducible nitric oxide synthase) in LPS
      stimulated macrophages by disrupting the transcription into mRNA of the genes
      coding for the associated transcription factors IRF-1 and NF-kappaB. The
      transcription of non-antiviral control genes was not perturbed by RRV-ADE
      infection, and de novo protein synthesis also was not significantly affected in
      RRV-ADE infected cells. The ADE pathway of infection allowed RRV to specifically
      target antiviral genes in macrophages, resulting in unrestricted virus
      replication. As ADE has been observed for several virus families and associated
      with disease and adverse vaccination outcomes, these findings may have broad
      relevance to viral disease formation and antiviral vaccination strategies.

PMID- 10954538
TI  - Relationship between retroviral DNA integration and gene expression.
AB  - Although retroviruses can integrate their DNA into a large number of sites in the
      host genome, factors controlling the specificity of integration remain
      controversial and poorly understood. To assess the effects of transcriptional
      activity on integration in vivo, we created quail cell clones containing a
      construct with a minigene cassette, whose expression is controlled by the
      papilloma virus E2 protein. From these clones we derived transcriptionally active
      subclones expressing the wild-type E2 protein and transcriptionally silent
      subclones expressing a mutant E2 protein that binds its target DNA but is unable
      to activate transcription. By infecting both clones and subclones with avian
      leukosis virus and using a PCR-based assay to determine viral DNA integration
      patterns, we were able to assess the effects of both protein binding and
      transcriptional activity on retroviral DNA integration. Contrary to the
      hypothesis that transcriptional activity enhances integration, we found an
      overall decrease in integration into our gene cassette in subclones expressing
      the wild-type E2 protein. We also found a decrease in integration into our gene
      cassette in subclones expressing the mutant E2 protein, but only into the protein
      binding region. Based on these findings, we propose that transcriptionally active
      DNA is not a preferred target for retroviral integration and that transcriptional
      activity may in fact be correlated with a decrease in integration.

PMID- 10954539
TI  - Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered
      rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell
      culture.
AB  - Three mutants of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (V106A, V179D, and Y181C), which occur in clinical isolates and
      confer resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs),
      were analyzed for RNA- and DNA-dependent DNA polymerization and RNase H cleavage.
      All mutants demonstrated processivities of polymerization that were
      indistinguishable from wild-type enzyme under conditions in which deoxynucleoside
      triphosphates were not limiting. The V106A reverse transcriptase demonstrated a
      three- to fourfold slowing of both DNA 3'-end-directed and RNA 5'-end-directed
      RNase H cleavage relative to both wild-type and V179D enzymes, similar to what
      was observed for P236L in a previously published study (P. Gerondelis et al., J.
      Virol. 73:5803-5813, 1999). In contrast, the Y181C reverse transcriptase
      demonstrated a selective acceleration of the secondary RNase H cleavage step
      during both modes of RNase H cleavage. The relative replication fitness of these
      mutants in H9 cells was assessed in parallel infections as well as in growth
      competition experiments. Of the NNRTI-resistant mutants, V179D was more fit than
      Y181C, and both of these mutants were more fit than V106A, which demonstrated the
      greatest reduction in RNase H cleavage. These findings, in combination with
      results from previous work, suggest that abnormalities in RNase H cleavage are a
      common characteristic of HIV-1 mutants resistant to NNRTIs and that combined
      reductions in the rates of DNA 3'-end- and RNA 5'-end-directed cleavages are
      associated with significant reductions in the replication fitness of HIV-1.

PMID- 10954540
TI  - Intracellular Cre-mediated deletion of the unique packaging signal carried by a
      herpes simplex virus type 1 recombinant and its relationship to the cleavage
      packaging process.
AB  - To gain further insight on the function of the herpes simplex virus type 1 (HSV
      1) packaging signal (a sequence), we constructed a recombinant virus containing a
      unique a sequence, which was flanked by two loxP sites in parallel orientation.
      The phenotype of this recombinant, named HSV-1 LaL, was studied in cell lines
      which either express or do not express Cre recombinase. Although LaL virus
      multiplication was only slightly reduced in standard cell lines, its growth was
      strongly inhibited in Cre-expressing cells. In these cells, a sequences were
      detected mostly in low-molecular-weight DNA circles, indicating that they had
      been excised from virus DNA by site-specific recombination. Deletion of the a
      sequences from the viral genome resulted in the accumulation of uncleaved
      replication intermediates, as observed by pulsed-field gel electrophoresis. B
      type capsids also accumulated in these cells, as shown both by electron
      microscopy and by sucrose gradient sedimentation. Further examination of the
      status of a sequences in Cre-expressing cells indicated that high-level
      amplification of this sequence can occur in the absence of the cleavage-packaging
      process. Moreover, the amplified a signals in small circular DNA molecules
      remained uncleaved, indicating that these molecules were not able to efficiently
      interact with the cleavage-packaging machinery. The cleavage-packaging machinery
      and the structural proteins required to assemble virions were, however,
      functional in HSV-1 LaL-infected Cre-expressing cells, since this system could be
      used to package plasmid DNA harboring an origin of virus replication and one
      normal a signal. This is the first study in which accumulation both of uncleaved
      replication intermediates and of B capsids has been obtained in the presence of
      the full set of proteins required to package virus DNA.

PMID- 10954541
TI  - Differential dynamics of CD4(+) and CD8(+) T-lymphocyte proliferation and
      activation in acute simian immunodeficiency virus infection.
AB  - Although lymphocyte turnover in chronic human immunodeficiency virus and simian
      immunodeficiency virus (SIV) infection has been extensively studied, there is
      little information on turnover in acute infection. We carried out a prospective
      kinetic analysis of lymphocyte proliferation in 13 rhesus macaques inoculated
      with pathogenic SIV. A short-lived dramatic increase in circulating Ki-67(+)
      lymphocytes observed at 1 to 4 weeks was temporally related to the onset of SIV
      replication. A 5- to 10-fold increase in Ki-67(+) CD8(+) T lymphocytes and a 2-
      to 3-fold increase in Ki-67(+) CD3(-) CD8(+) natural killer cells accounted for
      >85% of proliferating lymphocytes at peak proliferation. In contrast, there was
      little change in the percentage of Ki-67(+) CD4(+) T lymphocytes during acute
      infection, although transient increases in Ki-67(-) and Ki-67(+) CD4(+) T
      lymphocytes expressing CD69, Fas, and HLA-DR were observed. A two- to fourfold
      decline in CD4(+) T lymphocytes expressing CD25 and CD69 was seen later in SIV
      infection. The majority of Ki-67(+) CD8(+) T lymphocytes were phenotypically
      CD45RA(-) CD49d(hi) Fas(hi) CD25(-) CD69(-) CD28(-) HLA-DR(-) and persisted at
      levels twofold above baseline 6 months after SIV infection. Increased CD8(+) T
      lymphocyte proliferation was associated with cell expansion, paralleled the onset
      of SIV-specific cytotoxic T-lymphocyte activity, and had an oligoclonal
      component. Thus, divergent patterns of proliferation and activation are exhibited
      by CD4(+) and CD8(+) T lymphocytes in early SIV infection and may determine how
      these cells are differentially affected in AIDS.

PMID- 10954542
TI  - Synergistic upregulation of interleukin-8 secretion from pulmonary epithelial
      cells by direct and monocyte-dependent effects of respiratory syncytial virus
      infection.
AB  - Respiratory syncytial virus (RSV) infection is the major cause of severe
      bronchiolitis in infants. Pathology of this infection is partly due to excessive
      proinflammatory leukocyte influx mediated by chemokines. Although direct
      infection of the respiratory epithelium by RSV may induce chemokine secretion,
      little is known about the role of cytokine networks. We investigated the effects
      of conditioned medium (CM) from RSV-infected monocytes (RSV-CM) on respiratory
      epithelial (A549) cell chemokine release. RSV-CM, but not control CM (both at a
      1:5 dilution), stimulated interleukin-8 (IL-8) secretion from A549 cells within 2
      h, and secretion increased over 72 h to 11,360 +/- 1,090 pg/ml without affecting
      cell viability. In contrast, RSV-CM had only a small effect on RANTES secretion.
      RSV-CM interacted with direct RSV infection to synergistically amplify IL-8
      secretion from respiratory epithelial cells (levels of secretion at 48 h were as
      follows: RSV-CM alone, 8,140 +/- 2,160 pg/ml; RSV alone, 12,170 +/- 300 pg/ml;
      RSV-CM plus RSV, 27,040 +/- 5,260 pg/ml; P < 0.05). RSV-CM induced degradation of
      IkappaBalpha within 5 min but did not affect IkappaBbeta. RSV-CM activated
      transient nuclear binding of NF-kappaB within 1 h, while activation of NF-IL6 was
      delayed until 8 h and was still detectable at 24 h. Promoter-reporter analysis
      demonstrated that NF-kappaB binding was essential and that NF-IL6 was important
      for IL-8 promoter activity in RSV-CM-activated cells. Blocking experiments
      revealed that the effects of RSV-CM depended on monocyte-derived IL-1 but that
      tumor necrosis factor alpha was not involved in this network. In summary, RSV
      infection of monocytes results in and amplifies direct RSV-mediated IL-8
      secretion from respiratory epithelial cells by an NF-kappaB-dependent, NF-IL6
      requiring mechanism.

PMID- 10954543
TI  - Natural genetic exchanges between vaccine and wild poliovirus strains in humans.
AB  - In a previous study of poliovirus vaccine-derived strains isolated from patients
      with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that
      a high proportion (over 50%) of viruses had a recombinant genome. Most were
      intertypic vaccine/vaccine recombinants. However, some had restriction fragment
      length polymorphism (RFLP) profiles different from those of poliovirus vaccine
      strains. We demonstrate here that five such recombinants, of 88 VAPP strains
      examined, carried sequences of wild (nonvaccine) origin. To identify the parental
      wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to
      look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating
      poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one
      case was the donor identified, and it was a wild type 1 poliovirus. For the other
      four vaccine/wild recombinants, the wild parent could not be identified. The
      possibility that the wild sequences were of a non-poliovirus-enterovirus origin
      could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from
      a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an
      isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine
      derived sequences in the 3' moiety of their genome. All these results suggest
      that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus
      enteroviruses, are also a natural means of evolution for poliovirus vaccine
      strains.

PMID- 10954545
TI  - Analysis of Mason-Pfizer monkey virus Gag domains required for capsid assembly in
      bacteria: role of the N-terminal proline residue of CA in directing particle
      shape.
AB  - Mason-Pfizer monkey virus (M-PMV) preassembles immature capsids in the cytoplasm
      prior to transporting them to the plasma membrane. Expression of the M-PMV Gag
      precursor in bacteria results in the assembly of capsids indistinguishable from
      those assembled in mammalian cells. We have used this system to investigate the
      structural requirements for the assembly of Gag precursors into procapsids. A
      series of C- and N-terminal deletion mutants progressively lacking each of the
      mature Gag domains (matrix protein [MA]-pp24/16-p12-capsid protein [CA]
      nucleocapsid protein [NC]-p4) were constructed and expressed in bacteria. The
      results demonstrate that both the CA and the NC domains are necessary for the
      assembly of macromolecular arrays (sheets) but that amino acid residues at the N
      terminus of CA define the assembly of spherical capsids. The role of these N
      terminal domains is not based on a specific amino acid sequence, since both MA-CA
      NC and p12-CA-NC polyproteins efficiently assemble into capsids. Residues N
      terminal of CA appear to prevent a conformational change in which the N-terminal
      proline plays a key role, since the expression of a CA-NC protein lacking this
      proline results in the assembly of spherical capsids in place of the sheets
      assembled by the CA-NC protein.

PMID- 10954544
TI  - Growth factor-independent proliferation of erythroid cells infected with Friend
      spleen focus-forming virus is protein kinase C dependent but does not require Ras
      GTP.
AB  - Interaction of erythropoietin (Epo) with its cell surface receptor activates
      signal transduction pathways which result in the proliferation and
      differentiation of erythroid cells. Infection of erythroid cells with the Friend
      spleen focus-forming virus (SFFV) leads to the interaction of the viral envelope
      glycoprotein with the Epo receptor and renders these cells Epo independent. We
      previously reported that SFFV induces Epo independence by constitutively
      activating components of several Epo signal transduction pathways, including the
      Jak-Stat and the Raf-1/mitogen-activated protein kinase (MAPK) pathways. To
      further evaluate the mechanism by which SFFV activates the Raf-1/MAPK pathway, we
      investigated the effects of SFFV on upstream components of this pathway, and our
      results indicate that SFFV activates Shc and Grb2 and that this leads to Ras
      activation. While studies with a dominant-negative Ras indicated that Ras was
      required for Epo-induced proliferation of normal erythroid cells, the Epo
      independent growth of SFFV-infected cells can still occur in the absence of Ras,
      although at reduced levels. In contrast, protein kinase C (PKC) was shown to be
      required for the Epo-independent proliferation of SFFV-infected cells. Further
      studies indicated that PKC, which is thought to be involved in the activation of
      both Raf-1 and MAPK, was required only for the activation of MAPK, not Raf-1, in
      SFFV-infected cells. Our results indicate that Ras and PKC define two distinct
      signals converging on MAPK in both Epo-stimulated and SFFV-infected erythroid
      cells and that activation of only PKC is sufficient for the Epo-independent
      proliferation of SFFV-infected cells.

PMID- 10954546
TI  - Expression of secreted cytokine and chemokine inhibitors by ectromelia virus.
AB  - The production of secreted proteins that bind cytokines and block their activity
      has been well characterized as an immune evasion strategy of the orthopoxviruses
      vaccinia virus (VV) and cowpox virus (CPV). However, very limited information is
      available on the expression of similar cytokine inhibitors by ectromelia virus
      (EV), a virulent natural mouse pathogen that causes mousepox. We have
      characterized the expression and binding properties of three major secreted
      immunomodulatory activities in 12 EV strains and isolates. Eleven of the 12 EVs
      expressed a soluble, secreted 35-kDa viral chemokine binding protein with
      properties similar to those of homologous proteins from VV and CPV. All of the
      EVs expressed soluble, secreted receptors that bound to mouse, human, and rat
      tumor necrosis factor alpha. We also detected the expression of a soluble,
      secreted interleukin-1beta (IL-1beta) receptor (vIL-1betaR) by all of the EVs. EV
      differed from VV and CPV in that binding of human (125)I-IL-1beta to the EV vIL
      1betaR could not be detected. Nevertheless, the EV vIL-1betaR prevented the
      interaction of human and mouse IL-1beta with cellular receptors. There are
      significant differences in amino acid sequence between the EV vIL-1betaR and its
      VV and CPV homologs which may account for the results of the binding studies. The
      conservation of these activities in EV suggests evolutionary pressure to maintain
      them in a natural poxvirus infection. Mousepox represents a useful model for the
      study of poxvirus pathogenesis and immune evasion. These findings will facilitate
      future study of the role of EV immunomodulatory factors in the pathogenesis of
      mousepox.

PMID- 10954547
TI  - Identification of carbohydrate-binding domains in the attachment proteins of type
      1 and type 3 reoviruses.
AB  - The reovirus attachment protein, sigma1, is responsible for strain-specific
      patterns of viral tropism in the murine central nervous system and receptor
      binding on cultured cells. The sigma1 protein consists of a fibrous tail domain
      proximal to the virion surface and a virion-distal globular head domain. To
      better understand mechanisms of reovirus attachment to cells, we conducted
      studies to identify the region of sigma1 that binds cell surface carbohydrate.
      Chimeric and truncated sigma1 proteins derived from prototype reovirus strains
      type 1 Lang (T1L) and type 3 Dearing (T3D) were expressed in insect cells by
      using a baculovirus vector. Assessment of expressed protein susceptibility to
      proteolytic cleavage, binding to anti-sigma1 antibodies, and oligomerization
      indicates that the chimeric and truncated sigma1 proteins are properly folded. To
      assess carbohydrate binding, recombinant sigma1 proteins were tested for the
      capacity to agglutinate mammalian erythrocytes and to bind sialic acid presented
      on glycophorin, the cell surface molecule bound by type 3 reovirus on human
      erythrocytes. Using a panel of two wild-type and ten chimeric and truncated
      sigma1 proteins, the sialic acid-binding domain of type 3 sigma1 was mapped to a
      region of sequence proposed to form the more amino terminal of two predicted beta
      sheet structures in the tail. This unit corresponds to morphologic region T(iii)
      observed in computer-processed electron micrographs of sigma1 protein purified
      from virions. In contrast, the homologous region of T1L sigma1 sequence was not
      implicated in carbohydrate binding; rather, sequences in the distal portion of
      the tail known as the neck were required. Results of these studies demonstrate
      that a functional receptor-binding domain, which uses sialic acid as its ligand,
      is contained within morphologic region T(iii) of the type 3 sigma1 tail.
      Furthermore, our findings indicate that T1L and T3D sigma1 proteins contain
      different arrangements of receptor-binding domains.

PMID- 10954548
TI  - Efficient cell infection by Moloney murine leukemia virus-derived particles
      requires minimal amounts of envelope glycoprotein.
AB  - Retrovirus entry into cells is mediated by specific interactions between the
      retrovirally encoded Env envelope glycoprotein and a host cell surface receptor.
      Though a number of peptide motifs responsible for the structure as well as for
      the binding and fusion activities of Env have been identified, only a few
      quantitative data concerning the infection process are available. Using an
      inducible expression system, we have expressed various amounts of ecotropic and
      amphotropic Env at the surfaces of Moloney murine leukemia virus-derived vectors
      and assayed for the infectivity of viral particles. Contrary to the current view
      that numerous noncooperative Env-viral receptor interactions are required for
      cell infection, we report here that very small amounts of Env are sufficient for
      optimal infection. However, increasing Env density clearly accelerates the rate
      at which infectious attachment to cells occurs. Moreover, our data also show that
      a surprisingly small number of Env molecules are sufficient to drive infection,
      albeit at a reduced efficiency, and that, under conditions of low expression, Env
      molecules act cooperatively. These observations have important consequences for
      our understanding of natural retroviral infection as well as for the design of
      cell-targeted infection techniques involving retroviral vectors.

PMID- 10954549
TI  - Avian nephritis virus (ANV) as a new member of the family Astroviridae and
      construction of infectious ANV cDNA.
AB  - The complete RNA genome of the avian nephritis virus (ANV) associated with acute
      nephritis in chickens has been molecularly cloned and sequenced. Excluding the
      poly(A) tail, the genome comprises 6,927 nucleotides and contains three
      sequential open reading frames (ORFs). The first ORF (ORF 1a) contains a sequence
      encoding a serine protease motif, and the second ORF (ORF 1b) has a sequence
      encoding an RNA-dependent RNA polymerase. ORF 1a may be linked to the second ORF
      by a ribosomal frameshifting mechanism. The third ORF (ORF 2) may encode the
      virion structural proteins as a polyprotein precursor. Two RNAs, probably genonic
      and subgenonic RNA (7.5 and 3.0 kb), were detected in the cytoplasm of ANV
      infected cells. ANV and human astroviruses have the same genonic organization,
      and both are characterized by the presence of two RNA bands. The amino acid
      homologies of the products of ORF 1a, 1b, and 2 were 20.3, 41.9, and 25.8% to
      products of the corresponding ORFs of human astrovirus serotype 1 (A/88 Newcastle
      strain). We have constructed a genonic-length cDNA clone of ANV to test whether
      the in vitro transcript is infectious. When a chicken kidney cell culture was
      transfected with RNA transcribed in vitro and the cDNA clone, infectious virus
      was produced with cytopathic effects in the absence of trypsin. These
      observations suggested that the ANV (G-4260 strain) is a new genus of the family
      Astroviridae.

PMID- 10954550
TI  - Patterns of changes in human immunodeficiency virus type 1 V3 sequence
      populations late in infection.
AB  - We have used a V3-specific heteroduplex tracking assay (V3-HTA) with probes from
      two different human immunodeficiency virus type 1 (HIV-1) subtypes to examine the
      extent and pace of HIV-1 evolution late in infection. Twenty-four subjects with
      advanced HIV-1 infection (CD4(+) T-cell count, <100/microl) and stable viral
      loads were studied using blood plasma samples collected over a study period of
      approximately 9 months, during which time most of the subjects were treated with
      reverse transcriptase inhibitors. The V3-HTA patterns from the first and last
      time points were evaluated initially to determine the amounts of change in V3
      sequence populations, which were primarily changes in abundance in preexisting
      sequence populations. Three of the 24 subjects had major changes (greater than
      50% total change in the relative abundance of the sequence populations), 11
      subjects had intermediate changes (10 to 50% total change), and 10 subjects had
      minimal changes (less than 10% total change). The average total amount of change
      was between two- and threefold greater in subjects with X4-like variants,
      although there was no correlation between average viral load and the presence of
      X4-like variants. V3-HTA patterns in monthly samples from 11 of the subjects were
      also compared. In two subjects, the amount of change exceeded 40% in a 1-month
      period. Overall, the pace of change in V3 populations varied between subjects and
      was not constant within a subject over time. Sequence analysis of the V3 variants
      showed that R5-like variants (not containing any X4-associated substitutions)
      continued to be maintained in three subjects in the presence of X4-like variants,
      indicating that X4 variants do not always outgrow R5 variants. The coreceptor
      usage of the V3 sequences from two subjects was determined using a cell fusion
      assay. One subject had an X4 variant that was maintained at a low level for at
      least 9 months, during which time the predominant variants were R5X4
      (dualtropic), while in the second subject the reverse situation was observed. One
      of the dualtropic variants had a novel sequence motif in V3, suggesting another
      evolutionary pathway to altered tropism. These studies begin to probe the
      complexities and pace of V3 evolution in vivo, revealing dynamic patterns of
      change among multiple V3 sequence variants in a subset of subjects.

PMID- 10954552
TI  - Selective inhibition of splicing at the avian sarcoma virus src 3' splice site by
      direct-repeat posttranscriptional cis elements.
AB  - The direct-repeat elements (dr1) of avian sarcoma virus (ASV) and leukosis virus
      have the properties of constitutive transport elements (CTEs), which facilitate
      cytoplasmic accumulation of unspliced RNA. It is thought that these elements
      represent binding sites for cellular factors. Previous studies have indicated
      that in the context of the avian sarcoma virus genome, precise deletion of both
      ASV dr1 elements results in a very low level of virus replication. This is
      characterized by a decreased cytoplasmic accumulation of unspliced RNA and a
      selective increase in spliced src mRNA. Deletion of either the upstream or
      downstream dr1 results in a delayed-replication phenotype. To determine if the
      same regions of the dr1 mediate inhibition of src splicing and unspliced RNA
      transport, point mutations in the upstream and downstream elements were studied.
      In the context of viral genomes with single dr1 elements, the effects of the
      mutations on virus replication and increases in src splicing closely paralleled
      the effects of the mutations on CTE activity. For mutants strongly affecting CTE
      activity and splicing, unspliced RNA but not spliced RNA turned over in the
      nucleus more rapidly than wild-type RNA. In the context of wild-type virus
      containing two dr1 elements, mutations of either element that strongly affect CTE
      activity caused a marked delay of virus replication and a selective increase in
      src splicing. However, the turnover of the mutant unspliced RNA as well as the
      spliced mRNA species did not differ significantly from that of the wild type.
      These results suggest the dr1 elements in ASV act to selectively inhibit src
      splicing and that both elements contribute to the fitness of the wild-type virus.
      However, a single dr1 element is sufficient to stabilize unspliced RNA.

PMID- 10954551
TI  - Early alterations of the receptor-binding properties of H1, H2, and H3 avian
      influenza virus hemagglutinins after their introduction into mammals.
AB  - Interspecies transmission of influenza A viruses circulating in wild aquatic
      birds occasionally results in influenza outbreaks in mammals, including humans.
      To identify early changes in the receptor binding properties of the avian virus
      hemagglutinin (HA) after interspecies transmission and to determine the amino
      acid substitutions responsible for these alterations, we studied the HAs of the
      initial isolates from the human pandemics of 1957 (H2N2) and 1968 (H3N2), the
      European swine epizootic of 1979 (H1N1), and the seal epizootic of 1992 (H3N3),
      all of which were caused by the introduction of avian virus HAs into these
      species. The viruses were assayed for their ability to bind the synthetic
      sialylglycopolymers 3'SL-PAA and 6'SLN-PAA, which contained, respectively, 3'
      sialyllactose (the receptor determinant preferentially recognized by avian
      influenza viruses) and 6'-sialyl(N-acetyllactosamine) (the receptor determinant
      for human viruses). Avian and seal viruses bound 6'SLN-PAA very weakly, whereas
      the earliest available human and swine epidemic viruses bound this polymer with a
      higher affinity. For the H2 and H3 strains, a single mutation, 226Q-->L,
      increased binding to 6'SLN-PAA, while among H1 swine viruses, the 190E-->D and
      225G-->E mutations in the HA appeared important for the increased affinity of the
      viruses for 6'SLN-PAA. Amino acid substitutions at positions 190 and 225 with
      respect to the avian virus consensus sequence are also present in H1 human
      viruses, including those that circulated in 1918, suggesting that substitutions
      at these positions are important for the generation of H1 human pandemic strains.
      These results show that the receptor-binding specificity of the HA is altered
      early after the transmission of an avian virus to humans and pigs and, therefore,
      may be a prerequisite for the highly effective replication and spread which
      characterize epidemic strains.

PMID- 10954553
TI  - Retracing the evolutionary pathways of human immunodeficiency virus type 1
      resistance to protease inhibitors: virus fitness in the absence and in the
      presence of drug.
AB  - Human immunodeficiency virus type 1 (HIV-1) resistance to protease inhibitors
      (PI) is a major obstacle to the full success of combined antiretroviral therapy.
      High-level resistance to these compounds is the consequence of stepwise
      accumulation of amino acid substitutions in the HIV-1 protease (PR), following
      pathways that usually differ from one inhibitor to another. The selective
      advantage conferred by resistance mutations may depend upon several parameters:
      the impact of the mutation on virus infectivity in the presence or absence of
      drug, the nature of the drug, and its local concentration. Because drug
      concentrations in vivo are subject to extensive variation over time and display a
      markedly uneven tissue distribution, the parameters of selection for HIV-1
      resistance to PI in treated patients are complex and poorly understood. In this
      study, we have reconstructed a large series of HIV-1 mutants that carry single or
      combined mutations in the PR, retracing the accumulation pathways observed in
      ritonavir-, indinavir-, and saquinavir-treated patients. We have then measured
      the phenotypic resistance and the drug-free infectivity of these mutant viruses.
      A deeper insight into the evolutionary value of HIV-1 PR mutants came from a
      novel assay system designed to measure the replicative advantage of mutant
      viruses as a function of drug concentration. By tracing the resultant fitness
      profiles, we determined the range of drug concentrations for which mutant viruses
      displayed a replicative advantage over the wild type and the extent of this
      advantage. Fitness profiles were fully consistent with the order of accumulation
      of resistance mutations observed in treated patients and further emphasise the
      key importance of local drug concentration in the patterns of selection of drug
      resistant HIV-1 mutants.

PMID- 10954554
TI  - Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen
      mediates dimerization, transcriptional repression, and targeting to nuclear
      bodies.
AB  - Human herpesvirus 8 (HHV-8; also known as Kaposi's sarcoma-associated
      herpesvirus) is the causative agent of Kaposi's sarcoma and certain B-cell
      lymphomas. In most infected cells, HHV-8 establishes a latent infection
      characterized by the expression of latency-associated nuclear antigen (LANA)
      encoded by open reading frame 73. Although unrelated by sequence, there are
      functional similarities between LANA and the EBNA-1 protein of Epstein-Barr
      virus. Both accumulate as subnuclear speckles and are required for maintenance of
      the viral episome. EBNA-1 also regulates viral gene expression and is required
      for cell immortalization, suggesting that LANA performs similar functions in the
      context of HHV-8 infection. Here we show that LANA forms stable dimers, or
      possibly higher-order multimers, and that this is mediated by a conserved region
      in the C terminus. By expressing a series of truncations, we show that both the N
      and C-terminal regions localize to the nucleus, although only the C terminus
      accumulates as nuclear speckles characteristic of the intact protein. Lastly, we
      show that LANA can function as a potent transcriptional repressor when tethered
      to constitutively active promoters via a heterologous DNA-binding domain. Domains
      in both the N and C termini mediate repression. This suggests that one function
      of LANA is to suppress the expression of the viral lytic genes or cellular genes
      involved in the antiviral response.

PMID- 10954555
TI  - Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T
      lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme
      linked immunospot assay.
AB  - Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL)
      responses play a major role in the antiviral immune response, but the relative
      contribution of CTL responses restricted by different HLA class I molecules is
      less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of
      Caucasoid populations and is even more highly prevalent in Asian populations, but
      yet no CTL epitopes restricted by these alleles have been defined. Here we report
      the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes,
      using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot)
      assays and using CTL clones and lines in cytolytic assays. The dominant HLA-B60
      restricted epitope, Nef peptide KEKGGLEGL, was targeted by all eight subjects
      with B60 and also by both subjects with B61 studied. This study additionally
      establishes the utility of the Elispot assay as a more rapid and efficient method
      of defining novel CTL epitopes. This approach will help to define new CTL
      epitopes that may play an important role in the immune control of HIV-1.

PMID- 10954556
TI  - CD4-Negative cells bind human immunodeficiency virus type 1 and efficiently
      transfer virus to T cells.
AB  - The ability of human immunodeficiency virus strain MN (HIV(MN)), a T-cell line
      adapted strain of HIV, and X4 and R5 primary isolates to bind to various cell
      types was investigated. In general, HIV(MN) bound to cells at higher levels than
      did the primary isolates. Virus bound to both CD4-positive (CD4(+)) and CD4
      negative (CD4(-)) cells, including neutrophils, Raji cells, tonsil mononuclear
      cells, erythrocytes, platelets, and peripheral blood mononuclear cells (PBMC),
      although virus bound at significantly higher levels to PBMC. However, there was
      no difference in the amount of HIV that bound to CD4-enriched or CD4-depleted
      PBMC. Virus bound to CD4(-) cells was up to 17 times more infectious for T cells
      in cocultures than was the same amount of cell-free virus. Virus bound to
      nucleated cells was significantly more infectious than virus bound to
      erythrocytes or platelets. The enhanced infection of T cells by virus bound to
      CD4(-) cells was not due to stimulatory signals provided by CD4(-) cells or
      infection of CD4(-) cells. However, anti-CD18 antibody substantially reduced the
      enhanced virus replication in T cells, suggesting that virus that bound to the
      surface of CD4(-) cells is efficiently passed to CD4(+) T cells during cell-cell
      adhesion. These studies show that HIV binds at relatively high levels to CD4(-)
      cells and, once bound, is highly infectious for T cells. This suggests that virus
      binding to the surface of CD4(-) cells is an important route for infection of T
      cells in vivo.

PMID- 10954557
TI  - Interaction of cellular proteins with the 5' end of Norwalk virus genomic RNA.
AB  - The lack of a susceptible cell line and an animal model for Norwalk virus (NV)
      infection has prompted the development of alternative strategies to generate in
      vitro RNAs that approximate the authentic viral genome. This approach has allowed
      the study of viral RNA replication and gene expression. In this study, using
      mobility shift and cross-linking assays, we detected several cellular proteins
      from HeLa and CaCo-2 cell extracts that bind to, and form stable complexes with,
      the first 110 nucleotides of the 5' end of NV genomic RNA, a region previously
      predicted to form a double stem-loop structure. These proteins had molecular
      weights similar to those of the HeLa cellular proteins that bind to the internal
      ribosomal entry site of poliovirus RNA. HeLa proteins La, PCBP-2, and PTB, which
      are important for poliovirus translation, and hnRNP L, which is possibly
      implicated in hepatitis C virus translation, interact with NV RNA. These protein
      RNA interactions are likely to play a role in NV translation and/or replication.

PMID- 10954558
TI  - Initiation of DNA replication within oriP is dispensable for stable replication
      of the latent Epstein-Barr virus chromosome after infection of established cell
      lines.
AB  - The 165-kb circularized chromosome of Epstein-Barr virus (EBV) is replicated in
      latently infected cells once per cell cycle by host proteins during S phase.
      Replication initiates at multiple sites on latent EBV chromosomes, including
      within a 1.8-kb region called oriP, which can provide both replication and
      stabilization for recombinant plasmids in the presence of the EBV-encoded
      protein, EBNA-1. Replication initiates at or near the dyad symmetry component
      (DS) of oriP, which depends on multiple EBNA-1 binding sites for activity. To
      test the importance of the replication function of oriP, the DS was deleted from
      the viral genome. EBV mutants lacking the DS and carrying a selectable gene could
      establish latent infections in BL30 cells, in which circular, mutant viral
      chromosomes were stably maintained. Analysis of replication fork movement using
      two-dimensional gel electrophoresis showed that the deletion of the DS reduced
      the initiation events to an undetectable level within the oriP region so that
      this segment was replicated exclusively by forks entering the region from either
      direction. A significant slowing or stalling of replication forks that occurs
      normally at the approximate position of the DS was also eliminated by deletion of
      the DS. The results confirm the DS as both a replication origin and a place where
      replication forks pause. Since the replication function of oriP is dispensable at
      least in certain cell lines, the essential role of EBNA-1 for infection of these
      cell lines is likely to be that of stabilizing the EBV chromosome by associating
      with the 30-bp repeats of oriP. The results also imply that in established cell
      lines, the EBV chromosome can be efficiently replicated entirely from origins
      that are activated by cellular factors. Presumably, initiation of replication at
      the DS, mediated by EBNA-1, is important for the natural life cycle of EBV,
      perhaps in establishing latent infections of normal B cells.

PMID- 10954559
TI  - Study of full-length porcine endogenous retrovirus genomes with envelope gene
      polymorphism in a specific-pathogen-free Large White swine herd.
AB  - Specific-pathogen-free (SPF) swine appear to be the most appropriate candidate
      for pig to human xenotransplantation. Still, the risk of endogenous retrovirus
      transmission represents a major obstacle, since two human-tropic porcine
      endogenous retroviruses (PERVs) had been characterized in vitro (P. Le Tissier,
      J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss, Nature 389:681-682,
      1997). Here we addressed the question of PERV distribution in a French Large
      White SPF pig herd in vivo. First, PCR screening for previously described PERV
      envelope genes envA, envB, and envC (D. E. Akiyoshi, M. Denaro, H. Zhu, J. L.
      Greenstein, P. Banerjee, and J. A. Fishman, J. Virol. 72:4503-4507, 1998; Le
      Tissier et al., op. cit.). demonstrated ubiquity of envA and envB sequences,
      whereas envC genes were absent in some animals. On this basis, selective out
      breeding of pigs of remote origin might be a means to reduce proviral load in
      organ donors. Second, we investigated PERV genome carriage in envC negative
      swine. Eleven distinct full-length PERV transcripts were isolated. The sequence
      of the complete envelope open reading frame was determined. The deduced amino
      acid sequences revealed the existence of four clones with functional and five
      clones with defective PERV PK-15 A- and B-like envelope sequences. The occurrence
      of easily detectable levels of PERV variants in different pig tissues in vivo
      heightens the need to assess PERV transmission in xenotransplantation animal
      models.

PMID- 10954560
TI  - Early steps of polyomavirus entry into cells.
AB  - The mechanism by which murine polyomavirus penetrates cells and arrives at the
      nucleus, the site of viral replication, is not well understood. Simian virus 40
      and JC virus, two closely related members of the polyomavirus subfamily, use
      caveola- and clathrin-mediated uptake pathways for entry, respectively. The data
      presented here indicate that compounds that block endocytosis of both caveola-
      and clathrin-derived vesicles have no effect on polyomavirus infectivity.
      Polyomavirus does not appear to colocalize with either clathrin light chain or
      caveolin-1 by immunofluorescence microscopy. Additionally, expression of a
      dominant-negative form of dynamin I has no effect on polyomavirus uptake and
      infectivity. Therefore, polyomavirus uptake occurs through a class of uncoated
      vesicles in a clathrin-, caveolin-1-, and dynamin I-independent manner.

PMID- 10954561
TI  - The simian virus 40 core origin contains two separate sequence modules that
      support T-antigen double-hexamer assembly.
AB  - Using subfragments of the simian virus 40 (SV40) core origin, we demonstrate that
      two alternative modules exist for the assembly of T-antigen (T-ag) double
      hexamers. Pentanucleotides 1 and 3 and the early palindrome (EP) constitute one
      assembly unit, while pentanucleotides 2 and 4 and the AT-rich region constitute a
      second, relatively weak, assembly unit. Related studies indicate that on the unit
      made up of pentanucleotide 1 and 3 and the EP assembly unit, the first hexamer
      forms on pentanucleotide 1 and that owing to additional protein-DNA and protein
      protein interactions, the second hexamer is able to form on pentanucleotide 3.
      Oligomerization on the unit made up of pentanucleotide 2 and 4 and the AT-rich
      region is initiated by assembly of a hexamer on pentanucleotide 4; subsequent
      formation of the second hexamer takes place on pentanucleotide 2. Given that
      oligomerization on the SV40 origin is limited to double-hexamer formation, it is
      likely that only a single module is used for the initial assembly of T-ag double
      hexamers. Finally, we discuss the evidence that nucleotide hydrolysis is required
      for the remodeling events that result in the utilization of the second assembly
      unit.

PMID- 10954562
TI  - Phosphorylation of simian virus 40 T antigen on Thr 124 selectively promotes
      double-hexamer formation on subfragments of the viral core origin.
AB  - Cell cycle-dependent phosphorylation of simian virus 40 (SV40) large tumor
      antigen (T-ag) on threonine 124 is essential for the initiation of viral DNA
      replication. A T-ag molecule containing a Thr-->Ala substitution at this position
      (T124A) was previously shown to bind to the SV40 core origin but to be defective
      in DNA unwinding and initiation of DNA replication. However, exactly what step in
      the initiation process is defective as a result of the T124A mutation has not
      been established. Therefore, to better understand the control of SV40
      replication, we have reinvestigated the assembly of T124A molecules on the SV40
      origin. Herein it is demonstrated that hexamer formation is unaffected by the
      phosphorylation state of Thr 124. In contrast, T124A molecules are defective in
      double-hexamer assembly on subfragments of the core origin containing single
      assembly units. We also report that T124A molecules are inhibitors of T-ag double
      hexamer formation. These and related studies indicate that phosphorylation of T
      ag on Thr 124 is a necessary step for completing the assembly of functional
      double hexamers on the SV40 origin. The implications of these studies for the
      cell cycle control of SV40 DNA replication are discussed.

PMID- 10954563
TI  - Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease.
AB  - The contribution of immune system cells to the propagation of transmissible
      encephalopathies is not well understood. To determine how follicular dendritic
      cells (FDC) may act, we challenged lymphotoxin beta null and wild-type (wt)
      controls with a Creutzfeldt-Jakob disease (CJD) agent. There was only a small
      difference in incubation time to clinical disease even after peripheral challenge
      with low infectious doses (31 in a total of 410 days). Brain pathology with
      extensive microglial infiltration, identified by keratan sulfate, as well as
      astrocytic hypertrophy, was also equivalent in all groups despite the fact that
      null mice had neither FDC nor splenic metallophilic macrophages that filter
      particulate antigen. Because FDC accumulate pathologic prion protein (PrP) in
      infected but not wt mice, we studied the cellular distribution of PrP by confocal
      microscopy. The majority of pathologic PrP collected on the plasma membrane of
      FDC, as identified by the Ca(+2)-binding protein S100A. This surface distribution
      suggested that agent aggregated with pathologic PrP might spread by cell-to-cell
      contacts. While several types of leukocytes may be involved in agent
      dissemination, cells of myeloid lineage were found to be infectious. Moreover,
      perivascular tracks of microglia and abnormal PrP after intraperitoneal
      inoculation were consistent with hematogenous spread. In summary, FDC are not
      required for CJD agent spread from the periphery, although FDC may enhance spread
      through surface accumulation of pathologic PrP. While it is still not clear where
      the infectious agent replicates, macrophages can sequester appreciable levels of
      infectivity and hence act as reservoirs for prolonged latent infection.

PMID- 10954565
TI  - Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and
      construction of AAV2 vectors with altered tropism.
AB  - Adeno-associated virus type 2 (AAV2) has proven to be a valuable vector for gene
      therapy. Characterization of the functional domains of the AAV capsid proteins
      can facilitate our understanding of viral tissue tropism, immunoreactivity, viral
      entry, and DNA packaging, all of which are important issues for generating
      improved vectors. To obtain a comprehensive genetic map of the AAV capsid gene,
      we have constructed 93 mutants at 59 different positions in the AAV capsid gene
      by site-directed mutagenesis. Several types of mutants were studied, including
      epitope tag or ligand insertion mutants, alanine scanning mutants, and epitope
      substitution mutants. Analysis of these mutants revealed eight separate
      phenotypes. Infectious titers of the mutants revealed four classes. Class 1
      mutants were viable, class 2 mutants were partially defective, class 3 mutants
      were temperature sensitive, and class 4 mutants were noninfectious. Further
      analysis revealed some of the defects in the class 2, 3, and 4 mutants. Among the
      class 4 mutants, a subset completely abolished capsid formation. These mutants
      were located predominantly, but not exclusively, in what are likely to be beta
      barrel structures in the capsid protein VP3. Two of these mutants were insertions
      at the N and C termini of VP3, suggesting that both ends of VP3 play a role that
      is important for capsid assembly or stability. Several class 2 and 3 mutants
      produced capsids that were unstable during purification of viral particles. One
      mutant, R432A, made only empty capsids, presumably due to a defect in packaging
      viral DNA. Additionally, five mutants were defective in heparan binding, a step
      that is believed to be essential for viral entry. These were distributed into two
      amino acid clusters in what is likely to be a cell surface loop in the capsid
      protein VP3. The first cluster spanned amino acids 509 to 522; the second was
      between amino acids 561 and 591. In addition to the heparan binding clusters,
      hemagglutinin epitope tag insertions identified several other regions that were
      on the surface of the capsid. These included insertions at amino acids 1, 34,
      138, 266, 447, 591, and 664. Positions 1 and 138 were the N termini of VP1 and
      VP2, respectively; position 34 was exclusively in VP1; the remaining surface
      positions were located in putative loop regions of VP3. The remaining mutants,
      most of them partially defective, were presumably defective in steps of viral
      entry that were not tested in the preliminary screening, including intracellular
      trafficking, viral uncoating, or coreceptor binding. Finally, in vitro
      experiments showed that insertion of the serpin receptor ligand in the N-terminal
      regions of VP1 or VP2 can change the tropism of AAV. Our results provide
      information on AAV capsid functional domains and are useful for future design of
      AAV vectors for targeting of specific tissues.

PMID- 10954566
TI  - The majority of duck hepatitis B virus reverse transcriptase in cells is
      nonencapsidated and is bound to a cytoplasmic structure.
AB  - The hepadnavirus reverse transcriptase binds cotranslationally to the viral
      pregenomic RNA. This ribonucleoprotein complex is then encapsidated into nascent
      viral core particles, where the reverse transcriptase copies the viral RNA into
      DNA. Here we report that 75% of the duck hepatitis B virus reverse transcriptase
      present in transfected LMH cells does not follow this well-known pathway but
      rather exists in the cell separate from the core protein or nucleocapsids. The
      nonencapsidated reverse transcriptase is also abundant in infected duck liver.
      The nonencapsidated reverse transcriptase exists as a complex set of isoforms
      that are most likely produced by posttranslational modification. Interestingly,
      only the smallest of these isoforms is encapsidated into viral core particles.
      The nonencapsidated reverse transcriptase is bound to a large cellular
      cytoplasmic structure(s) in a detergent-sensitive complex. The cellular
      distribution of the reverse transcriptase only partially overlaps that of the
      core protein, and this distribution is unaffected by blocking encapsidation.
      These observations raise the possibilities that the metabolic fate of the reverse
      transcriptase may be posttranscriptionally regulated and that the reverse
      transcriptase may have roles in the viral replication cycle beyond its well-known
      function in copying the viral genome.

PMID- 10954564
TI  - Transcriptional regulation of the Kaposi's sarcoma-associated herpesvirus viral
      interferon regulatory factor gene.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, open
      reading frame (ORF) K9 encodes a viral interferon regulatory factor (vIRF) that
      functions as a repressor for interferon-mediated signal transduction.
      Consequently, this gene is thought to play an important role in the
      tumorigenicity of KSHV. To understand the molecular mechanisms underlying vIRF
      expression, we studied the transcriptional regulation of this gene. Experiments
      using 5' rapid amplification of cDNA ends and primer extension revealed that vIRF
      had different transcriptional patterns during the latent and lytic phases. The
      promoter region of the minor transcript, which was mainly expressed in uninduced
      BCBL-1 cells, did not contain a canonical TATA box, but a cap-like element and an
      initiator element flanked the transcription start site. The promoter of the major
      transcript, which was mainly expressed in tetradecanoyl phorbol acetate-induced
      BCBL-1 cells, contained a canonical TATA box. A luciferase reporter assay using a
      deletion mutant of the vIRF promoter and a mutation in the TATA box showed that
      the TATA box was critical for the lytic activity of vIRF. The promoter activity
      in the latent phase was eight times stronger than that of the empty vector but
      was less than 10% of the activity in the lytic phase. Therefore, KSHV may use
      different functional promoter elements to regulate the expression of vIRF and to
      antagonize the cell's interferon-mediated antiviral activity. We have also
      identified a functional domain in the ORF 50 protein, an immediate-early gene
      product that is mainly encoded by ORF 50. The ORF 50 protein transactivated the
      vIRF and DNA polymerase promoters in BCBL-1, 293T, and CV-1 cells. Deleting one
      of its two putative nuclear localization signals (NLSs) resulted in failure of
      the ORF 50 protein to localize to the nucleus and consequently abrogated its
      transactivating activity. We further confirmed that the N-terminal region of the
      ORF 50 protein included an NLS domain. We found that this domain was sufficient
      to translocate beta-galactosidase to the nucleus. Analysis of deletions within
      the vIRF promoter suggested that two sequence domains were important for its
      transactivation by the ORF 50 protein, both of which included putative SP-1 and
      AP-1 binding sites. Competition gel shift assays demonstrated that SP-1 bound to
      these two domains, suggesting that the SP-1 binding sites in the vIRF promoter
      are involved in its transactivation by ORF 50.

PMID- 10954567
TI  - Functional dissection of the major structural protein of bluetongue virus:
      identification of key residues within VP7 essential for capsid assembly.
AB  - A lattice of VP7 trimers forms the surface of the icosahedral bluetongue virus
      (BTV) core. To investigate the role of VP7 oligomerization in core assembly, a
      series of residues for substitution were predicted based on crystal structures of
      BTV type 10 VP7 molecule targeting the monomer-monomer contacts within the
      trimer. Seven site-specific substitution mutations of VP7 have been created using
      cDNA clones and were employed to produce seven recombinant baculoviruses. The
      effects of these mutations on VP7 solubility, ability to trimerize and formation
      of core-like particles (CLPs) in the presence of the scaffolding VP3 protein,
      were investigated. Of the seven VP7 mutants examined, three severely affected the
      stability of CLP, while two other mutants had lesser effect on CLP stability.
      Only one mutant had no apparent effect on the formation of the stable capsid. One
      mutant in which the conserved tyrosine at residue 271 (lower domain helix 6) was
      replaced by arginine formed insoluble aggregates, implying an effect in the
      folding of the molecule despite the prediction that such a change would be
      accommodated. All six soluble VP7 mutants were purified, and their ability to
      trimerize was examined. All mutants, including those that did not form stable
      CLPs, assembled into stable trimers, implying that single substitution may not be
      sufficient to perturb the complex monomer-monomer contacts, although subtle
      changes within the VP7 trimer could destabilize the core. The study highlights
      some of the key residues that are crucial for BTV core assembly and illustrates
      how the structure of VP7 in isolation underrepresents the dynamic nature of the
      assembly process at the biological level.

PMID- 10954568
TI  - Localization of human immunodeficiency virus type 1 Gag and Env at the plasma
      membrane by confocal imaging.
AB  - Budding of lentiviruses occurs at the plasma membrane, but the preceding steps
      involved in particle assembly are poorly understood. Since the Gag polyprotein
      mediates virion assembly and budding, studies on the localization of Gag within
      the cell should provide insight into the mechanism of particle assembly. Here, we
      utilize biochemical fractionation techniques as well as high-resolution confocal
      imaging of live cells to demonstrate that Gag is localized at the plasma membrane
      in a striking punctate pattern. Mutation of the N-terminal myristoylation site
      results in the formation of large cytosolic complexes, whereas mutation of the N
      terminal basic residue cluster in the matrix domain redirects the Gag protein to
      a region partially overlapping the Golgi apparatus. In addition, we show that Gag
      and Env colocalize at the plasma membrane and that mistargeting of a mutant Gag
      to the Golgi apparatus alters the pattern of surface expression of Env.

PMID- 10954569
TI  - Potential dengue virus-triggered apoptotic pathway in human neuroblastoma cells:
      arachidonic acid, superoxide anion, and NF-kappaB are sequentially involved.
AB  - Direct in vivo evidence for the susceptibility of human neuronal cells to dengue
      virus has not been reported. In this study, we demonstrated that type 2 dengue
      (DEN-2) virus infection induced extensive apoptosis in the human neuroblastoma
      cell line SK-N-SH. Phospholipase A(2) (PLA(2)) was activated by DEN-2 infection,
      which led to the generation of arachidonic acid (AA). Inhibition of PLA(2)
      activity by the PLA(2) inhibitors, AACOCF(3) and ONO-RS-082, diminished DEN-2
      virus-induced apoptosis. In contrast, the cyclooxygenase inhibitors aspirin and
      indomethacin, thought to increase AA accumulation by blocking AA catabolism,
      enhanced apoptosis. Exogenous AA induced apoptosis in a dose-dependent manner.
      Superoxide anion, which is thought to be generated through the AA-activated NADPH
      oxidase, was increased after infection. Pretreatment with superoxide dismutase
      (SOD) protected cells against DEN-2 virus-induced apoptosis. Furthermore,
      generation of superoxide anion was blocked by AACOCF(3). In addition, the
      transcription factors, NF-kappaB and c-Jun, were found to be activated after DEN
      2 virus infection. However, pretreatment of cells with oligodeoxynucleotides
      containing NF-kappaB, but not c-Jun, binding sites (transcription factor decoy)
      strongly prevented dengue virus-induced apoptosis. The finding that AACOCF(3) and
      SOD significantly block activation of NF-kappaB suggests that this activation is
      derived from the AA-superoxide anion pathway. Our results indicate that DEN-2
      virus infection of human neuroblastoma cells triggers an apoptotic pathway
      through PLA(2) activation to superoxide anion generation and subsequently to NF
      kappaB activation. This apoptotic effect can be either directly derived from the
      action of AA and superoxide anion on mitochondria or indirectly derived from the
      products of apoptosis-related genes activated by NF-kappaB.

PMID- 10954570
TI  - Membrane targeting properties of a herpesvirus tegument protein-retrovirus Gag
      chimera.
AB  - The retroviral Gag protein is capable of directing the production and release of
      virus-like particles in the absence of all other viral components. Budding
      normally occurs after Gag is transported to the plasma membrane by its membrane
      targeting and -binding (M) domain. In the Rous sarcoma virus (RSV) Gag protein,
      the M domain is contained within the first 86 amino acids. When M is deleted,
      membrane association and budding fail to occur. Budding is restored when M is
      replaced with foreign membrane-binding sequences, such as that of the Src
      oncoprotein. Moreover, the RSV M domain is capable of targeting heterologous
      proteins to the plasma membrane. Although the solution structure of the RSV M
      domain has been determined, the mechanism by which M specifically targets Gag to
      the plasma membrane rather than to one or more of the large number of internal
      membrane surfaces (e.g., the Golgi apparatus, endoplasmic reticulum, and nuclear,
      mitochondrial, or lysosomal membranes) is unknown. To further investigate the
      requirements for targeting proteins to discrete cellular locations, we have
      replaced the M domain of RSV with the product of the unique long region 11
      (U(L)11) gene of herpes simplex virus type 1. This 96-amino-acid myristylated
      protein is thought to be involved in virion transport and envelopment at internal
      membrane sites. When the first 100 amino acids of RSV Gag (including the M
      domain) were replaced by the entire UL11 sequence, the chimeric protein localized
      at and budded into the Golgi apparatus rather than being targeted to the plasma
      membrane. Myristate was found to be required for this specific targeting, as were
      the first 49 amino acids of UL11, which contain an acidic cluster motif. In
      addition to shedding new light on UL11, these experiments demonstrate that RSV
      Gag can be directed to internal cellular membranes and suggest that regions
      outside of the M domain do not contain a dominant plasma membrane-targeting
      motif.

PMID- 10954571
TI  - Granulocyte-macrophage colony-stimulating factor priming plus papillomavirus E6
      DNA vaccination: effects on papilloma formation and regression in the cottontail
      rabbit papillomavirus--rabbit model.
AB  - A cottontail rabbit papillomavirus (CRPV) E6 DNA vaccine that induces significant
      protection against CRPV challenge was used in a superior vaccination regimen in
      which the cutaneous sites of vaccination were primed with an expression vector
      encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine
      that induces differentiation and local recruitment of professional antigen
      presenting cells. This treatment induced a massive influx of major
      histocompatibility complex class II-positive cells. In a vaccination-challenge
      experiment, rabbit groups were treated by E6 DNA vaccination, GM-CSF DNA
      inoculation, or a combination of both treatments. After two immunizations,
      rabbits were challenged with CRPV at low, moderate, and high stringencies and
      monitored for papilloma formation. As expected, all clinical outcomes were
      monotonically related to the stringency of the viral challenge. The results
      demonstrate that GM-CSF priming greatly augmented the effects of CRPV E6
      vaccination. First, challenge sites in control rabbits (at the moderate challenge
      stringency) had a 0% probability of remaining disease free, versus a 50%
      probability in E6-vaccinated rabbits, and whereas GM-CSF alone had no effect, the
      interaction between GM-CSF priming and E6 vaccination increased disease-free
      survival to 67%. Second, the incubation period before papilloma onset was
      lengthened by E6 DNA vaccination alone or to some extent by GM-CSF DNA
      inoculation alone, and the combination of treatments induced additive effects.
      Third, the rate of papilloma growth was reduced by E6 vaccination and, to a
      lesser extent, by GM-CSF treatment. In addition, the interaction between the E6
      and GM-CSF treatments was synergistic and yielded more than a 99% reduction in
      papilloma volume. Finally, regression occurred among the papillomas that formed
      in rabbits treated with the E6 vaccine and/or with GM-CSF, with the highest
      regression frequency occurring in rabbits that received the combination
      treatment.

PMID- 10954572
TI  - Influenza virus assembly: effect of influenza virus glycoproteins on the membrane
      association of M1 protein.
AB  - Influenza virus matrix protein (M1), a critical protein required for virus
      assembly and budding, is presumed to interact with viral glycoproteins on the
      outer side and viral ribonucleoprotein on the inner side. However, because of the
      inherent membrane-binding ability of M1 protein, it has been difficult to
      demonstrate the specific interaction of M1 protein with hemagglutinin (HA) or
      neuraminidase (NA), the influenza virus envelope glycoproteins. Using Triton X
      100 (TX-100) detergent treatment of membrane fractions and floatation in sucrose
      gradients, we observed that the membrane-bound M1 protein expressed alone or
      coexpressed with heterologous Sendai virus F was totally TX-100 soluble but the
      membrane-bound M1 protein expressed in the presence of HA and NA was
      predominantly detergent resistant and floated to the top of the density gradient.
      Furthermore, both the cytoplasmic tail and the transmembrane domain of HA
      facilitated binding of M1 to detergent-resistant membranes. Analysis of the
      membrane association of M1 in the early and late phases of the influenza virus
      infectious cycle revealed that the interaction of M1 with mature glycoproteins
      which associated with the detergent-resistant lipid rafts was responsible for the
      detergent resistance of membrane-bound M1. Immunofluorescence analysis by
      confocal microscopy also demonstrated that, in influenza virus-infected cells, a
      fraction of M1 protein colocalized with HA and associated with the HA in transit
      to the plasma membrane via the exocytic pathway. Similar results for
      colocalization were obtained when M1 and HA were coexpressed and HA transport was
      blocked by monensin treatment. These studies indicate that both HA and NA
      interact with influenza virus M1 and that HA associates with M1 via its
      cytoplasmic tail and transmembrane domain.

PMID- 10954573
TI  - The valine anticodon and valylatability of Peanut clump virus RNAs are not
      essential but provide a modest competitive advantage in plants.
AB  - The role of valine aminoacylation of the two genomic RNAs of Peanut clump virus
      (PCV) was studied by comparing the amplification in vivo of RNAs with GAC,
      GDeltaC, or CCA anticodons in the tRNA-like structure (TLS) present at the 3' end
      of each viral RNA. The PCV RNA1 TLS of isolate PCV2 possesses a GAC anticodon and
      is capable of highly efficient valylation, whereas the RNA2 TLS has a GDeltaC
      anticodon that does not support valylation. The presence in RNA1 of GDeltaC or
      CCA anticodons that conferred nonvalylatability resulted in about 2- to 4-fold
      and a 14- to 24-fold reduction, respectively, in RNA accumulations in tobacco BY
      2 protoplasts inoculated with the RNA1 variants together with wild-type
      RNA2(GDeltaC). No differences in RNA levels were observed among protoplasts
      inoculated with the three variant RNA2s in the presence of wild-type RNA1(GAC).
      All combinations of valylatable and nonvalylatable RNAs 1 and 2 were similarly
      infectious in Nicotiana benthamiana plants, and viral RNAs accumulated to similar
      levels; all input TLS sequences were present unchanged in apical leaves. In
      direct competition experiments in N. benthamiana plants, however, both RNA1 and
      RNA2 with GAC valylatable anticodons outcompeted the nonvalylatable variants. We
      conclude that valylation provides a small but significant replicational advantage
      to both PCV RNAs. Sequence analysis of the TLS from RNA2 of a second PCV isolate,
      PO2A, revealed the presence of an intact GAC valine anticodon, suggesting that
      the differential valylation of the genomic RNAs of isolate PCV2 is not a general
      characteristic of PCV.

PMID- 10954574
TI  - Coinfection of SCID-hu Thy/Liv mice with human herpesvirus 6 and human
      immunodeficiency virus type 1.
AB  - Human herpesvirus 6 (HHV-6) has been proposed as a potential cofactor in the
      progression of human immunodeficiency virus type 1 (HIV-1) disease. We used the
      SCID-hu Thy/Liv mouse model to evaluate the in vivo interactions between HHV-6
      and HIV-1. Our results demonstrate that HHV-6 and HIV-1 can simultaneously
      replicate in the human thymus in vivo. In this model, however, the presence of
      one virus appears not to modify the replication or cytopathicity of the other.

PMID- 10954575
TI  - Novel transcriptional regulatory signals in the adeno-associated virus terminal
      repeat A/D junction element.
AB  - Adeno-associated virus (AAV) type 2 vectors transfer stable, long-term gene
      expression to diverse cell types in vivo. Many gene therapy applications require
      the control of long-term transgene expression, and AAV vectors, similar to other
      gene transfer systems, are being evaluated for delivery of regulated gene
      expression cassettes. Previously, we (R. P. Haberman, T. J. McCown, and R. J.
      Samulski, Gene Ther. 5:1604-1611, 1998) demonstrated the use of the tetracycline
      responsive system for long-term regulated expression in rat brains. In that
      study, we also observed residual expression in the "off" state both in vitro and
      in vivo, suggesting that the human cytomegalovirus (CMV) major immediate-early
      minimal promoter or other cis-acting elements (AAV terminal repeats [TR]) were
      contributing to this activity. In the present study, we identify that the AAV TR,
      minus the tetracycline-responsive minimal CMV promoter, will initiate mRNA
      expression from vector templates. Using deletion analysis and specific PCR
      derived TR reporter gene templates, we mapped this activity to a 37-nucleotide
      stretch in the A/D elements of the TR. Although the mRNA derived from the TR is
      generated from a non-TATA box element, the use of mutant templates failed to
      identify function of canonical initiator sequences as previously described.
      Finally, we demonstrated the presence of green fluorescent protein expression
      both in vitro and in vivo in brain by using recombinant virus carrying only the
      TR element. Since the AAV terminal repeat is a necessary component of all
      recombinant AAV vectors, this TR transcriptional activity may interfere with all
      regulated expression cassettes and may be a problem in the development of novel
      TR split gene vectors currently being considered for genes too large to be
      packaged.

PMID- 10954576
TI  - Detection and quantification of CD4(+) T cells with specificity for a new major
      histocompatibility complex class II-restricted influenza A virus matrix protein
      epitope in peripheral blood of influenza patients.
AB  - FVFTLTVPS was identified as the core sequence of a new major histocompatibility
      complex class II-restricted T-cell epitope of influenza virus matrix protein.
      Epitope-specific CD4(+) T cells were detected in the peripheral blood of patients
      with frequencies of up to 0.94%, depending on the number of additional terminal
      amino acids.

PMID- 10954577
TI  - Activation of the interferon-inducible 2'-5'-oligoadenylate synthetase gene by
      hepatitis C virus core protein.
AB  - The effects of hepatitis C virus (HCV) proteins on several signal transduction
      pathways in human nonneoplastic hepatocyte PH5CH8 cells were investigated using
      expression vectors encoding HCV proteins derived from HCV-infected human
      nonneoplastic cultured T-lymphocyte and hepatocyte cells (MT-2C and PH5CH7),
      which could support HCV replication. The amino acid sequences of HCV proteins
      obtained from HCV-infected human cells were identical or very close to the
      consensus sequences of the proteins derived from the original inoculum used for
      HCV infection. During the course of the study, we found that HCV core protein
      specifically activated the 40/46-kDa 2'-5'-oligoadenylate synthetase (2'-5'-OAS)
      gene promoter in a dose-dependent manner in different human hepatocyte cell lines
      (PH5CH8, HepG2, and PLC/PRF/5). We also found that the activation by core protein
      was further enhanced in the cells treated with alpha interferon. The expression
      of E1 or E2 envelope protein or nonstructural NS5A protein did not activate the
      2'-5'-OAS gene promoter. We demonstrated that the activation by core protein in
      the hepatocyte cells was suppressed by antisense RNA complementary to core
      encoding RNA. Deletion mutant analysis of core protein and deletion analysis of
      the 2'-5'-OAS gene promoter have been performed. Finally, we demonstrated that
      the activation of the 2'-5'-OAS gene occurred at the transcriptional level and
      furthermore demonstrated that the endogenous 2'-5'-OAS gene was also activated by
      core protein. This is the first report to show that a viral protein activated the
      2'-5'-OAS gene.

PMID- 10954579
TI  - Is the 135S poliovirus particle an intermediate during cell entry?
AB  - Poliovirus binding to its receptor (PVR) on the cell surface induces a
      conformational transition which generates an altered particle with a
      sedimentation value of 135S versus the 160S of the native virion. A number of
      lines of evidence suggest that the 135S particle is a cell entry intermediate.
      However, the low infection efficiencies of the 135S particle and the absence of
      detectable 135S particles during infection at 26 degrees C by the cold-adapted
      mutants argue against a role for the 135S particle during the cell entry process.
      We show here that binding of 135S-antibody complexes to the Fc receptor (CDw32)
      increases the infectivity of these particles by 2 to 3 orders of magnitude. Thus,
      the low efficiency of infection by 135S particles is due in part to the low
      binding affinity of these particles. In addition, we show that there is an
      additional stage in the entry process that is associated with RNA release. This
      stage occurs after formation of the 135S particle, is rate limiting during
      infection at 37 degrees C, but not at 26 degrees C, and is PVR independent. The
      data also demonstrate that during infection at 26 degrees C, the rate-limiting
      step is the PVR-mediated conversion of wild-type 160S particles to 135S
      particles. This suggests that during infection at 26 degrees C by the cold
      adapted viruses, 135S particles are formed, but they fail to accumulate to
      detectable levels because the subsequent post-135S particle events occur at a
      significantly faster rate than the initial conversion of 160S to 135S particles.
      These data support a model in which the 135S particle is an intermediate during
      poliovirus entry.

PMID- 10954578
TI  - Human immunodeficiency virus type 1 envelope epitope-specific CD4(+) T
      lymphocytes in simian/human immunodeficiency virus-infected and vaccinated rhesus
      monkeys detected using a peptide-major histocompatibility complex class II
      tetramer.
AB  - A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide
      complex was used to quantitate human immunodeficiency virus type 1 (HIV-1)
      envelope (Env)-specific CD4(+) T cells in vaccinated and in simian/human
      immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class
      II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) were employed to
      construct this tetrameric complex. A p46-specific proliferative response was seen
      in sorted, tetramer-binding, but not nonbinding, CD4(+) T cells, directly
      demonstrating that this response was mediated by the epitope-specific
      lymphocytes. Although staining of whole blood from 10 SHIV-infected Mamu
      DR*W201(+) rhesus monkeys failed to demonstrate tetramer-binding CD4(+) T cells
      (<0.02%), p46-stimulated peripheral blood mononuclear cells (PBMCs) from 9 of
      these 10 monkeys had detectable p46 tetramer-binding cells, comprising 0.5 to
      15.2% of the CD4(+) T cells. p46-stimulated PBMCs from 7 of 10 Mamu-DR*W201(+)
      monkeys vaccinated with a recombinant canarypox virus-HIV-1 env construct also
      demonstrated p46 tetramer-binding cells, comprising 0.9 to 7.2% of the CD4(+) T
      cells. Thus, Env p46-specific CD4(+) T cells can be detected by tetrameric Mamu
      DR*W201-p46 complex staining of PBMCs in both SHIV-infected and vaccinated rhesus
      monkeys. These epitope-specific cell populations appear to be present in
      peripheral blood at a very low frequency.

PMID- 10954580
TI  - Induction of mucosal homing virus-specific CD8(+) T lymphocytes by attenuated
      simian immunodeficiency virus.
AB  - Induction of virus-specific T-cell responses in mucosal as well as systemic
      compartments of the immune system is likely to be a critical feature of an
      effective AIDS vaccine. We investigated whether virus-specific CD8(+) lymphocytes
      induced in rhesus macaques by immunization with attenuated simian
      immunodeficiency virus (SIV), an approach that is highly effective in eliciting
      protection against mucosal challenge, express the mucosa-homing receptor
      alpha4beta7 and traffic to the intestinal mucosa. SIV-specific CD8(+) T cells
      expressing alpha4beta7 were detected in peripheral blood and intestine of
      macaques infected with attenuated SIV. In contrast, virus-specific T cells in
      blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus
      Ankara regimen did not express alpha4beta7. These results demonstrate the
      selective induction of SIV-specific CD8(+) T lymphocytes expressing alpha4beta7
      by a vaccine approach that replicates in mucosal tissue and suggest that
      induction of virus-specific lymphocytes that are able to home to mucosal sites
      may be an important characteristic of a successful AIDS vaccine.

PMID- 10954581
TI  - The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1
      replication at multiple stages.
AB  - We have recently demonstrated that the binding subunit (B-oligomer) of pertussis
      toxin (PTX-B) deactivates CCR5 and inhibits entry of R5 human immunodeficiency
      virus type 1 (HIV-1) strains in activated primary T lymphocytes (M. Alfano et
      al., J. Exp. Med. 190:597-605, 1999). We now present evidence that PTX-B also
      affects a post-entry step of HIV-1 replication. While PTX-B inhibited fusion
      induced by R5 but not that induced by X4 envelopes, it blocked infection of T
      cells with recombinant HIV-1 particles pseudotyped with R5, X4, and even murine
      leukemia virus or vesicular stomatitis virus envelopes. It also suppressed HIV-1
      RNA synthesis in cultures of infected peripheral blood mononuclear cells when new
      infections had been inhibited by zidovudine, and it reduced Tat-dependent
      expression of the luciferase reporter gene controlled by the HIV-1 long terminal
      repeat (LTR). Surprisingly, PTX-B did not affect expression from the
      cytomegalovirus promoter, nor did it reduce the basal (Tat-independent)
      expression from the LTR promoter. These results indicate that PTX-B inhibits HIV
      1 infection at both the entry and the post-entry stages of viral replication,
      with the post-entry activity specifically affecting transcription or stability of
      Tat-stimulated HIV-1 mRNAs.

PMID- 10954582
TI  - Detection and characterization of genetic recombination in cytopathic type 2
      bovine viral diarrhea viruses.
AB  - In cytopathic bovine viral diarrhea virus genotype 1 (BVDV1) isolates, insertions
      are reported at position A (amino acid [aa] 1535) and position B (aa 1589).
      Insertions at position B predominate. In this survey it was found that in BVDV2,
      insertions at position A predominate. Possible reasons for this difference in
      relative frequency are discussed.

PMID- 10954583
TI  - The 17 nucleotides downstream from the env gene stop codon are important for
      murine leukemia virus packaging.
AB  - We have identified a previously unknown nucleotide sequence important for the
      packaging of murine leukemia virus. This nucleotide sequence is located
      downstream from the stop codon of the env gene but does not overlap the
      polypurine tract. Deletion of 17 bp from this region resulted in a more than 10
      fold decrease in viral titer. Consistent with this result, the deletion mutant
      showed a 20- to 30-fold drop in the amount of virion RNA in the culture
      supernatant. The total amount of virion protein in the culture supernatant was
      comparable for the deletion mutant and the parental virus, suggesting that the
      mutant construct could release the empty viral particles. These results suggested
      that the packaging signal sequence might be present at the two extreme sites of
      the viral genome, one in the region around the splice donor sequence downstream
      from the 5' long terminal repeat (LTR) and the other immediately upstream from
      the 3' LTR. Implications for gene therapy, especially in regard to construction
      of retroviral vectors and packaging constructs, are discussed.

PMID- 10954584
TI  - Protein synthesis shut-off induced by influenza virus infection is independent of
      PKR activity.
AB  - The role of PKR activity in influenza virus-induced cell shut-off was studied by
      infection of PKR(+) or PKR(-) cell cultures and metabolic labeling in vivo. No
      differences in the synthesis of viral proteins or the decay of cellular protein
      synthesis were observed. To investigate the relevance of the inhibition of
      cellular pre-mRNA polyadenylation and nucleocytoplasmic transport in virus
      induced shut-off, we carried out similar experiments with mutant viruses lacking
      C-terminal sequences of NS1 protein. No differences in the shut-off induced by
      mutant versus wild-type viruses were observed, indicating that these nuclear
      events are not relevant for shut-off. The analysis of cytoplasmic mRNA stability
      indicated that the accumulation of viral mRNA during the infection correlated
      with the progressive decay of cellular mRNA, in both the wild type and an NS1
      deletion mutant.

PMID- 10954586
TI  - Puralpha: a multifunctional single-stranded DNA- and RNA-binding protein.
AB  - Puralpha is a ubiquitous, sequence-specific DNA- and RNA-binding protein which is
      highly conserved in eukaryotic cells. Puralpha has been implicated in diverse
      cellular functions, including transcriptional activation and repression,
      translation and cell growth. Moreover, this protein has been shown to be involved
      in regulating several human viruses which replicate in the central nervous system
      (CNS), including human immunodeficiency virus type I (HIV-1) and JC virus (JCV).
      Puralpha exerts part of its activity by interacting with cellular proteins,
      including pRb, E2F, cyclin A, Sp1 and members of the Y-box family of proteins,
      including YB-1 and MSY1, as well as viral proteins such as polyomavirus large T
      antigen and HIV-1 Tat. The ability of Puralpha to interact with its target DNA
      sequence and to associate with several viral and cellular proteins is modulated
      by RNA. Puralpha has also been shown to be involved in cell growth and
      proliferation. Its association with pRb, E2F and cyclin A coupled with its
      fluctuating levels throughout the cell cycle, position Puralpha as a crucial
      factor in the cell cycle. Moreover, microinjection studies demonstrate that
      Puralpha causes either a G(1) or G(2) arrest depending on the cell cycle time of
      injection. The gene encoding Puralpha has been localized to a human locus which
      is frequently deleted in myelogenous leukemias and other cancers and Puralpha
      gene deletions have been detected in many cases of lymphoid cancers. The
      following review details the structural characteristics of Puralpha, its family
      members and the involvement of this protein in regulating various cellular and
      viral genes, viral replication and cell growth.

PMID- 10954585
TI  - Antizyme expression: a subversion of triplet decoding, which is remarkably
      conserved by evolution, is a sensor for an autoregulatory circuit.
AB  - The efficiency of programmed ribosomal frameshifting in decoding antizyme mRNA is
      the sensor for an autoregulatory circuit that controls cellular polyamine levels
      in organisms ranging from the yeast Schizosaccharomyces pombe to Drosophila to
      mammals. Comparison of the frameshift sites and flanking stimulatory signals in
      many organisms now permits a reconstruction of the likely evolutionary path of
      the remarkably conserved mRNA sequences involved in the frameshifting.

PMID- 10954588
TI  - Functional analysis of putative restriction-modification system genes in the
      Helicobacter pylori J99 genome.
AB  - Helicobacter pylori is a gram-negative bacterium, which colonizes the gastric
      mucosa of humans and is implicated in a wide range of gastroduodenal diseases.
      The genomic sequences of two H.pylori strains, 26695 and J99, have been published
      recently. About two dozen potential restriction-modification (R-M) systems have
      been annotated in both genomes, which is far above the average number of R-M
      systems in other sequenced genomes. Here we describe a functional analysis of the
      16 putative Type II R-M systems in the H. pylori J99 genome. To express
      potentially toxic endonuclease genes, a unique vector was constructed, which
      features repression and antisense transcription as dual control elements. To
      determine the methylation activities of putative DNA methyltransferases, we
      developed polyclonal antibodies able to detect DNA containing N6-methyladenine or
      N4-methylcytosine. We found that <30% of the potential Type II R-M systems in
      H.pylori J99 strain were fully functional, displaying both endonuclease and
      methyltransferase activities. Helicobacter pylori may maintain a variety of
      functional R-M systems, which are believed to be a primitive bacterial 'immune'
      system, by alternatively turning on/off a subset of numerous R-M systems.

PMID- 10954587
TI  - Purification and characterization of a mammalian homolog of Escherichia coli MutY
      mismatch repair protein from calf liver mitochondria.
AB  - A protein homologous to the Escherichia coli MutY glycosylase, referred to as
      mtMYH, has been purified from calf liver mitochondria. SDS-polyacrylamide gel
      electrophoresis, western blot analysis as well as gel filtration chromatography
      predicted the molecular mass of the purified calf mtMYH to be 35-40 kDa. Gel
      mobility shift analysis showed that the purified mtMYH formed specific binding
      complexes with A/8-oxoG, G/8-oxoG and T/8-oxoG, weakly with C/8-oxoG, but not
      with A/G and A/C mismatches. The purified mtMYH exhibited DNA glycosylase
      activity removing adenine mispaired with G, C or 8-oxoG and weakly removing
      guanine mispaired with 8-oxoG. The mtMYH glycosylase activity was insensitive to
      high concentrations of NaCl and EDTA. The purified mtMYH cross-reacted with
      antibodies against both intact MutY and a peptide of human MutY homolog (hMYH).
      DNA glycosylase activity of mtMYH was inhibited by anti-MutY antibodies but not
      by anti-hMYH peptide antibodies. Together with the previously described
      mitochondrial MutT homolog (MTH1) and 8-oxoG glycosylase (OGG1, a functional MutM
      homolog), mtMYH can protect mitochondrial DNA from the mutagenic effects of 8
      oxoG.

PMID- 10954589
TI  - The N(8)-(2'-deoxyribofuranoside) of 8-aza-7-deazaadenine: a universal nucleoside
      forming specific hydrogen bonds with the four canonical DNA constituents.
AB  - The 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin-4-amine) N(8)-(2'
      deoxyribonucleoside) (2) which has an unusual glycosylation position was
      introduced as a universal nucleoside in oligonucleotide duplexes. These
      oligonucleotides were prepared by solid-phase synthesis employing phosphoramidite
      chemistry. Oligonucleotides incorporating the universal nucleoside 2 are capable
      of forming base pairs with the four normal DNA nucleosides without significant
      structural discrimination. The thermal stabilities of those duplexes are very
      similar and are only moderately reduced compared to those with regular Watson
      Crick base pairs. The universal nucleoside 2 belongs to a new class of compounds
      that form bidentate base pairs with all four natural DNA constituents through
      hydrogen bonding. The base pair motifs follow the Watson-Crick or the Hoogsteen
      mode. Also an uncommon motif is suggested for the base pair of 2 and dG. All of
      the new base pairs have a different shape compared to those of the natural DNA
      but fit well into the DNA duplex as the distance of the anomeric carbons
      approximates those of the common DNA base pairs.

PMID- 10954590
TI  - Transcriptional repression of BRCA1 by aberrant cytosine methylation, histone
      hypoacetylation and chromatin condensation of the BRCA1 promoter.
AB  - BRCA1 expression is repressed by aberrant cytosine methylation in sporadic breast
      cancer. We hypothesized that aberrant cytosine methylation of the BRCA1 promoter
      was associated with the transcriptionally repressive effects of histone
      hypoacetylation and chromatin condensation. To address this question, we
      developed an in vitro model of study using normal cells and sporadic breast
      cancer cells with known levels of BRCA1 transcript to produce a 1.4 kb 5
      methylcytosine map of the BRCA1 5' CpG island. While all cell types were densely
      methylated upstream of -728 relative to BRCA1 transcription start, all normal and
      BRCA1 expressing cells were non-methylated downstream of -728 suggesting that
      this region contains the functional BRCA1 5' regulatory region. In contrast, the
      non-BRCA1 expressing UACC3199 cells were completely methylated at all 75 CpGs.
      Chromatin immunoprecipitations showed that the UACC3199 cells were hypoacetylated
      at both histones H3 and H4 in the BRCA1 promoter compared to non-methylated BRCA1
      expressing cells. The chromatin of the methylated UACC3199 BRCA1 promoter was
      inaccessible to DNA-protein interactions. These data indicate that the epigenetic
      effects of aberrant cytosine methylation, histone hypoacetylation and chromatin
      condensation act together in a discrete region of the BRCA1 5' CpG island to
      repress BRCA1 transcription in sporadic breast cancer.

PMID- 10954591
TI  - Functional significance of conserved residues in the phosphohydrolase module of
      Escherichia coli MutT protein.
AB  - Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2'-dGTP (8-oxo-dGTP)
      to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine
      (8-oxo-G) into nascent DNA. Bacterial and mammalian homologs of MutT protein
      share the phosphohydrolase module (MutT: Gly37-->Gly59). By saturation
      mutagenesis of conserved residues in the MutT module, four of the 10 conserved
      residues (Gly37, Gly38, Glu53 and Glu57) were revealed to be essential to
      suppress spontaneous A:T-->C:G transversion mutation in a mutT(-) mutator strain.
      For the other six residues (Lys39, Glu44, Thr45, Arg52, Glu56 and Gly59), many
      positive mutants which can suppress the spontaneous mutation were obtained;
      however, all of the positive mutants for Glu44 and Arg52 either partially or
      inefficiently suppressed the mutation, indicating that these two residues are
      also important for MutT function. Several positive mutants for Lys39, Thr45,
      Glu56 and Gly59 efficiently decreased the elevated spontaneous mutation rate, as
      seen with the wild-type, hence, these four residues are non-essential for MutT
      function. As Lys38 and Glu55 in human MTH1, corresponding to the non-essential
      residues Lys39 and Glu56 in MutT, could not be replaced by any other residue
      without loss of function, different structural features between the two modules
      of MTH1 and MutT proteins are evident.

PMID- 10954593
TI  - Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA.
AB  - Werner syndrome (WS) is an autosomal recessive disease characterized by early
      onset of many features of aging, by an unusual spectrum of cancers, and by
      genomic instability. The WS protein (WRN) possesses 3'-->5' DNA helicase and
      associated ATPase activities, as well as 3'-->5' DNA exonuclease activity.
      Currently, WRN is the only member of the widely distributed RecQ DNA helicase
      family with documented exonuclease activity. It is not known whether deficiency
      of the exonuclease or helicase/ATPase activities of WRN, or all of them, is
      responsible for various elements of the WS phenotype. WRN exonuclease has limited
      homology to Escherichia coli RNaseD, a tRNA processing enzyme. We show here that
      WRN preferentially degrades synthetic DNA substrates containing alternate
      secondary structures, with an exonucleolytic mode of action suggestive of RNaseD.
      We present evidence that structure-dependent binding of WRN to DNA requires ATP
      binding, while DNA degradation requires ATP hydrolysis. Apparently, the
      exonuclease and ATPase act in concert to catalyze structure-dependent DNA
      degradation. We propose that WRN protein functions as a DNA processing enzyme in
      resolving aberrant DNA structures via both exonuclease and helicase activities.

PMID- 10954592
TI  - Expression of ZmMET1, a gene encoding a DNA methyltransferase from maize, is
      associated not only with DNA replication in actively proliferating cells, but
      also with altered DNA methylation status in cold-stressed quiescent cells.
AB  - A cDNA fragment encoding part of a DNA methyltransferase was isolated from maize.
      The putative amino acid sequence identically matched that deduced from a genomic
      sequence in the database (accession no. AF063403), and the corresponding gene was
      designated as ZmMET1. Bacterially expressed ZmMET1 actively methylated DNA in
      vitro. Transcripts of ZmMET1 could be shown to exclusively accumulate in actively
      proliferating cells of the meristems of mesocotyls and root apices, suggesting
      ZmMET1 expression to be associated with DNA replication. This was confirmed by
      simultaneous decrease of transcripts of ZmMET1 and histone H3, a marker for DNA
      replication, in seedlings exposed to wounding, desiccation and salinity, all of
      which suppress cell division. Cold stress also depressed both transcripts in root
      tissues. In contrast, however, accumulation of ZmMET1 transcripts in shoot
      mesocotyls was not affected by cold stress, whereas those for H3 sharply
      decreased. Such a differential accumulation of ZmMET1 transcripts was consistent
      with ZmMET1 protein levels as revealed by western blotting. Expression of ZmMET1
      is thus coexistent, but not completely dependent on DNA replication. Southern
      hybridization analysis with a methylation-sensitive restriction enzyme revealed
      that cold treatment induced demethylation of DNA in the Ac/Ds transposon region,
      but not in other genes, and that such demethylation primarily occurred in roots.
      These results suggested that the methylation level was decreased selectively by
      cold treatment, and that ZmMET1 may, at least partly, prevent such demethylation.

PMID- 10954594
TI  - Structure-function relationships of two closely related group IC3 intron
      ribozymes from Azoarcus and Synechococcus pre-tRNA.
AB  - The two group IC3 pre-tRNA introns from Azoarcus and Synechococcus share very
      analogous secondary structures. They are small group I ribozymes that possess
      only two peripheral domains, P2 and P9. However, the 3'-splice site hydrolysis
      activity of the Synechococcus ribozyme critically depends on P2 whereas that of
      Azoarcus does not, indicating that the structure-function relationships of the
      two ribozymes are strikingly different despite their structural resemblance. To
      identify the element(s) that determines the catalytic properties of these
      ribozymes, we undertook analyses of chimeric ribozymes prepared by swapping their
      structural elements. We found that the difference can be attributed to a small
      number of nucleotides within the conserved core region. Further analysis by
      employing in vitro selection revealed that a base triple interaction (P4bp3 x
      J6/7-2) is a critical element for determining activity and suggests the existence
      of a novel base quintuple involving the base triple P4bp5 x J8/7-5.

PMID- 10954595
TI  - Re-annotating the Mycoplasma pneumoniae genome sequence: adding value, function
      and reading frames.
AB  - Four years after the original sequence submission, we have re-annotated the
      genome of Mycoplasma pneumoniae to incorporate novel data. The total number of
      ORFss has been increased from 677 to 688 (10 new proteins were predicted in
      intergenic regions, two further were newly identified by mass spectrometry and
      one protein ORF was dismissed) and the number of RNAs from 39 to 42 genes. For 19
      of the now 35 tRNAs and for six other functional RNAs the exact genome positions
      were re-annotated and two new tRNA(Leu) and a small 200 nt RNA were identified.
      Sixteen protein reading frames were extended and eight shortened. For each ORF a
      consistent annotation vocabulary has been introduced. Annotation reasoning,
      annotation categories and comparisons to other published data on M.pneumoniae
      functional assignments are given. Experimental evidence includes 2-dimensional
      gel electrophoresis in combination with mass spectrometry as well as gene
      expression data from this study. Compared to the original annotation, we
      increased the number of proteins with predicted functional features from 349 to
      458. The increase includes 36 new predictions and 73 protein assignments
      confirmed by the published literature. Furthermore, there are 23 reductions and
      30 additions with respect to the previous annotation. mRNA expression data
      support transcription of 184 of the functionally unassigned reading frames.

PMID- 10954596
TI  - Loss of drug-stimulated topoisomerase II DNA breaks in living cells is different
      at two unrelated loci.
AB  - Topoisomerase II (top2) has been implicated in the initial steps of chromosomal
      translocations leading to leukemias and lymphomas, since it can generate DNA
      cleavage. To evaluate the effects of chromatin structure on enzyme-mediated
      cleavage, we determined the kinetics of loss of double-stranded DNA breaks
      stimulated by top2 poisons in Drosophila melanogaster Kc cells at two genomic
      regions that differ in chromatin structure. Moreover, cleavage loss was
      determined at 25 degrees C as well as after heat shock. Kinetics were dependent
      on the poison, nevertheless, loss rate overall was slow at the histone gene
      cluster, an active chromatin domain. At the repressed satellite III DNA, loss of
      cleavage was much faster and complete after 5 min in drug-free medium. In
      addition, differences were noted among sites that were closely spaced and equally
      intense. Following heat shock at 37 degrees C, we observed reduced cleavage
      levels and faster loss of breaks at the histone gene cluster. In vitro reversal
      could only partially explain the in vivo kinetics. Thus, the chromatin context of
      DNA breaks might play a role in the loss of top2 DNA breaks. The present findings
      suggest that irreversible cuts may more likely occur in active than silent loci.

PMID- 10954597
TI  - In vivo repair of methylation damage in Aag 3-methyladenine DNA glycosylase null
      mouse cells.
AB  - 3-Methyladenine (3MeA) DNA glycosylases initiate base excision repair by removing
      3MeA. These glycosylases also remove a broad spectrum of spontaneous and
      environmentally induced base lesions in vitro. Mouse cells lacking the Aag 3MeA
      DNA glycosylase (also known as the Mpg, APNG or ANPG DNA glycosylase) are
      susceptible to 3MeA-induced S phase arrest, chromosome aberrations and apoptosis,
      but it is not known if Aag is solely responsible for repair of 3MeA in vivo. Here
      we show that in AAG:(-/-) cells, 3MeA lesions disappear from the genome slightly
      faster than would be expected by spontaneous depurination alone, suggesting that
      there may be residual repair of 3MeA. However, repair of 3MeA is at least 10
      times slower in AAG:(-/-) cells than in AAG:(+/+) cells. Consequently, 24 h after
      exposure to [(3)H]MNU, 30% of the original 3MeA burden is intact in AAG:(-/-)
      cells, while 3MeA is undetectable in AAG:(+/+) cells. Thus, Aag is the major DNA
      glycosylase for 3MeA repair. We also investigated the in vivo repair kinetics of
      another Aag substrate, 7-methylguanine. Surprisingly, 7-methylguanine is removed
      equally efficiently in AAG:(+/+) and AAG:(-/-) cells, suggesting that another DNA
      glycosylase acts on lesions previously thought to be repaired by Aag.

PMID- 10954598
TI  - Complex patterns of inheritance of an imprinted murine transgene suggest
      incomplete germline erasure.
AB  - Here we report a transgenic mouse line that exhibits significant deviations from
      a classic pattern of parental imprinting. When the transgene is passed through
      the female germline, it is completely silenced in some offspring while in others
      expression is reduced. This variable expressivity does not appear to be the
      result of differences in the presence of unlinked modifiers. Female transmission
      of the transgene is associated with hypermethylation. The transgene is generally
      reactivated on passage through the male germline. Extended pedigrees reveal
      complex patterns of inheritance of the phenotype. The most likely explanation for
      this result is that the imprint is not completely erased and reset when passed
      through the germline of either sex. FISH analysis reveals that the transgene has
      integrated into chromosome 3 band E3, a region not known to carry imprinted
      genes, and the integration site shows no sign of allele-specific differential
      methylation. These findings, in conjunction with other recent work, raise the
      possibility that the introduction of foreign DNA into the mammalian genome,
      either through retrotransposition or transgenesis, may be associated with
      parental imprinting that is not always erased and reset during meiosis.

PMID- 10954599
TI  - RNA-binding characteristics of the chloroplast S1-like ribosomal protein CS1.
AB  - The chloroplast ribosomal protein CS1, the homolog of the bacterial ribosomal
      protein S1, is believed to be involved in the process of ribosome binding to mRNA
      during translation. Since translation control is an important step in chloroplast
      gene expression, and in order to study initiation complex formation, we studied
      the RNA-binding properties of CS1 protein. We found that most of the CS1 protein
      in spinach chloroplast co-purified with the 30S ribosomal subunit. The relative
      binding affinity of RNA to CS1 was determined using the UV-crosslinking
      competition assay. CS1 protein binds the ribohomopolymer poly(U) with a
      relatively high binding affinity. Very low binding affinities were obtained for
      the other ribohomopolymers, poly(G), poly(A) and poly(C). In addition, no
      specific binding of CS1, either in the 30S complex or as a recombinant purified
      protein, was obtained to the 5'-untranslated region of the mRNA in comparison to
      the other parts. RNA-binding experiments, in which the N- and C-termini of the
      protein were analyzed, revealed that the RNA-binding site is located in the C
      terminus half of the protein. These results suggest that CS1 does not direct the
      30S complex to the initiation codon of the translation site by specific binding
      to the 5'-untranslated region. In bacteria, specific binding is derived by base
      pairing between 16S rRNA and the Shine-Dalagarno sequences. In the chloroplast,
      nuclear encoded and gene-specific translation factors may be involved in the
      determination of specific binding of the 30S subunit to the initiator codon.

PMID- 10954600
TI  - Expanding the structural and functional diversity of RNA: analog uridine
      triphosphates as candidates for in vitro selection of nucleic acids.
AB  - Two analog uridine triphosphates tethering additional functionality, one a
      primary amino group and the second a mercapto group, were prepared and tested for
      their compatibility with in vitro RNA selection procedures. 5-(3
      Aminopropyl)uridine triphosphate (UNH(2)) as a uridine substitute was a more
      effective substrate for T7 RNA polymerase than 5-(2-mercaptoethyl)uridine
      triphosphate (USH). However, both functioned in transcription assays of 100 nt
      templates to generate RNA transcripts in quantities sufficient to initiate RNA
      selection procedures. Transcription of RNA pools with T7 RNA polymerase and
      UNH(2) or USH occurred with efficiencies of 43 and 29%, respectively, of the
      values obtained for native UTP transcription. In addition, the transcribed RNA
      containing roughly 25% UNH(2) residues exhibited better substrate properties for
      SuperScript(TM) II RNase H reverse transcriptase than did RNA transcripts
      containing approximately 25% of the USH analog. With either analog, both
      transcription and reverse transcription proceeded with high fidelity for
      insertion of the analog residue.

PMID- 10954601
TI  - Vaccinia topoisomerase and Cre recombinase catalyze direct ligation of activated
      DNA substrates containing a 3'-para-nitrophenyl phosphate ester.
AB  - DNA topoisomerases and DNA site-specific recombinases are involved in a diverse
      set of cellular processes but both function by making transient breaks in DNA.
      Type IB topoisomerases and tyrosine recombinases cleave DNA by
      transesterification of an active site tyrosine to generate a DNA-3'
      phosphotyrosyl-enzyme adduct and a free 5'-hydroxyl (5'-OH). Strand ligation
      results when the 5'-OH attacks the covalent complex and displaces the enzyme. We
      describe the synthesis of 3'-phospho-(para-nitrophenyl) oligonucleotides (3'-pNP
      DNAs), which mimic the natural 3'-phosphotyrosyl intermediate, and demonstrate
      that such pre-activated strands are substrates for DNA ligation by vaccinia
      topoisomerase and Cre recombinase. Ligation occurs by direct attack of a 5'-OH
      strand on the 3'-pNP DNA (i.e., without a covalent protein-DNA intermediate) and
      generates free para-nitrophenol as a product. The chromogenic DNA substrate
      allows ligation to be studied in real-time and in the absence of competing
      cleavage reactions and can be exploited for high-throughput screening of
      topoisomerase/recombinase inhibitors.

PMID- 10954603
TI  - Intercodon dinucleotides affect codon choice in plant genes.
AB  - In this work, 710 CDSs corresponding to over 290 000 codons equally distributed
      between Brassica napus, Arabidopsis thaliana, Lycopersicon esculentum, Nicotiana
      tabacum, Pisum sativum, Glycine max, Oryza sativa, Triticum aestivum, Hordeum
      vulgare and Zea mays were considered. For each amino acid, synonymous codon
      choice was determined in the presence of A, G, C or T as the initial nucleotide
      of the subsequent triplet; data were statistically analysed under the hypothesis
      of an independent assortment of codons. In 33.4% of cases, a frequency
      significantly (P: = 0.01) different from that expected was recorded. This was
      mainly due to a pervasive intercodon TpA and CpG deficiency. As a general rule,
      intercodon TpAs and CpGs were preferably replaced by CpAs and TpGs, respectively.
      In several instances, codon frequencies were also modified to avoid homotetramer
      and homotrimer formation, to reduce intercodon ApCs downstream (1,2) GG or AG
      dinucleotides, as well as to increase GpA or ApG intercodons under certain
      contexts. Since TpA, CpG and homotetra(tri)mer deficiency directly or indirectly
      accounted for 77% of significant variation in the codon frequency, it can be
      concluded that codon usage mirrors precise needs at the DNA structure level.
      Plant species exhibited a phylogenetically-related adaptation to structural
      constraints. Codon usage flexibility was reflected in strikingly different arrays
      of optimum codons for probe design.

PMID- 10954602
TI  - Strand invasion by mixed base PNAs and a PNA-peptide chimera.
AB  - Peptide nucleic acid oligomers (PNAs) have a remarkable ability to invade duplex
      DNA at polypurine-polypyrimidine target sequences. Applications for PNAs in
      medicine and biotechnology would increase if the rules governing their
      hybridization to mixed base sequences were also clear. Here we describe
      hybridization of PNAs to mixed base sequences and demonstrate that simple
      chemical modifications can enhance recognition. Easily synthesized and readily
      soluble eight and 10 base PNAs bind to plasmid DNA at an inverted repeat that is
      likely to form a cruciform structure, providing convenient tags for creating PNA
      plasmid complexes. PNAs also bind to mixed base sequences that cannot form
      cruciforms, suggesting that recognition is a general phenomenon. Rates of strand
      invasion are temperature dependent and can be enhanced by attaching PNAs to
      positively charged peptides. Our results support use of PNAs to access the
      information within duplex DNA and demonstrate that simple chemical modifications
      can make PNAs even more powerful agents for strand invasion. Simple strategies
      for enhancing strand invasion should facilitate the use of PNAs: (i) as
      biophysical probes of double-stranded DNA; (ii) to target promoters to control
      gene expression; and (iii) to direct sequence-specific mutagenesis.

PMID- 10954604
TI  - Levels of free PABP are limited by newly polyadenylated mRNA in early Spisula
      embryogenesis.
AB  - The poly(A) tail of eukaryotic mRNAs regulates translation and RNA stability
      through an association with the poly(A)-binding protein (PABP). The role of PABP
      in selective polyadenylation/deadenylation and translational
      recruitment/repression of maternal mRNAs that occurs in early development is not
      fully understood. Here, we report studies including UV-crosslinking and
      immunoblotting assays to characterise PABP in the early developmental stages of
      the clam Spisula solidissima. A single, 70 kDa PABP, whose sequence is highly
      homologous to vertebrate, yeast and plant PABPs, is detected in oocytes. The
      levels of clam PABP are constant in early embryogenesis, although its ability to
      crosslink labelled poly(A) is 'masked' shortly after fertilisation and remains so
      until the larval stage. Full RNA-binding potential of PABP in embryo lysates was
      achieved by brief denaturation with guanidinium hydrochloride followed by
      dilution for binding and crosslinking or by controlled treatment of lysates with
      Ca(2+)-dependent micrococcal nuclease. Masking of PABP, which accompanies
      cytoplasmic polyadenylation in maturing oocytes and in in vitro activated oocyte
      lysates, is very likely due to an association with mRNAs that bear new PABP
      target binding sites and thus prevent protein binding to the labelled A-rich
      probe. Functional implications of these findings as well as the potential
      application of this unmasking method to other RNA-binding proteins is discussed.

PMID- 10954605
TI  - The majority of human replication protein A remains complexed throughout the cell
      cycle.
AB  - Replication Protein A (RPA), the replicative single-strand DNA binding protein
      from eukaryotic cells, is a stable heterotrimeric complex consisting of three
      polypeptides. Cytological studies have investigated the subcellular distribution
      and association characteristics of the three RPA subunits during different stages
      of the cell cycle with varying results. In this study, various HeLa cell
      fractions were subjected to separation by either immunoprecipitation or velocity
      sedimentation. These separations were evaluated by immunoblotting for specific
      RPA subunits to determine whether the RPA in these fractions retains its
      heterotrimeric association. Immunoprecipitation of either the large (RPA70) or
      middle-sized (RPA32) subunit of RPA followed by immunoblotting for the other
      subunits demonstrate that RPA remains complexed throughout the G(1), S and G(2)
      phases of the cell cycle. Immunoprecipitation and sedimentation separations of
      both the nucleosolic and chromatin-bound RPA populations from both cycling and
      nocodazole-blocked cells showed that the majority of RPA remains complexed under
      all conditions examined. Consistent with previous reports, hypotonic extracts
      from 293 cells were shown to contain some RPA32 not complexed with RPA70. These
      results indicate that in some cell types, extracts may contain small amounts of
      RPA32 free of RPA70; however, in HeLa cells the majority of RPA clearly remains
      complexed as a heterotrimer throughout the cell cycle.

PMID- 10954606
TI  - Requirements for double-strand cleavage by chimeric restriction enzymes with zinc
      finger DNA-recognition domains.
AB  - This study concerns chimeric restriction enzymes that are hybrids between a zinc
      finger DNA-binding domain and the non-specific DNA-cleavage domain from the
      natural restriction enzyme FOK:I. Because of the flexibility of DNA recognition
      by zinc fingers, these enzymes are potential tools for cleaving DNA at
      arbitrarily selected sequences. Efficient double-strand cleavage by the chimeric
      nucleases requires two binding sites in close proximity. When cuts were mapped on
      the DNA strands, it was found that they occur in pairs separated by approximately
      4 bp with a 5' overhang, as for native FOK:I. Furthermore, amino acid changes in
      the dimer interface of the cleavage domain abolished activity. These results
      reflect a requirement for dimerization of the cleavage domain. The dependence of
      cleavage efficiency on the distance between two inverted binding sites was
      determined and both upper and lower limits were defined. Two different zinc
      finger combinations binding to non-identical sites also supported specific
      cleavage. Molecular modeling was employed to gain insight into the precise
      location of the cut sites. These results define requirements for effective
      targets of chimeric nucleases and will guide the design of novel specificities
      for directed DNA cleavage in vitro and in vivo.

PMID- 10954607
TI  - Differential effect of zinc finger deletions on the binding of CTCF to the
      promoter of the amyloid precursor protein gene.
AB  - High levels of transcription from the amyloid precursor protein promoter are
      dependent on the binding of CTCF to the APBbeta core recognition sequence located
      between positions -82 and -93 upstream from the transcriptional start site. CTCF
      comprises 727 amino acids and contains 11 zinc finger motifs arranged in tandem
      that are flanked by 267 amino acids on the N-terminal side and 150 amino acids on
      the C-terminal side. Deletion of either the N- or the C-terminal regions outside
      of the zinc finger domain had no detrimental effect on the binding of CTCF to
      APBbeta. However, internal deletions of zinc fingers 5-7 completely abolished
      binding. The binding of full-length CTCF generated a DNase I protected domain
      extending from position -78 to -116, which was interrupted by a hypersensitive
      site at position -99. Selective deletions from the N- and C-terminal sides of the
      zinc finger domain showed that the N-terminal end of the zinc finger domain was
      aligned toward the transcriptional start site. Furthermore, deletions of zinc
      fingers peripheral to the essential zinc fingers 5-7 decreased the stability of
      the binding complex by interrupting sequence-specific interactions.

PMID- 10954608
TI  - Structural basis of polyamine-DNA recognition: spermidine and spermine
      interactions with genomic B-DNAs of different GC content probed by Raman
      spectroscopy.
AB  - Four genomic DNAs of differing GC content (Micrococcus luteus, 72% GC;
      Escherichia coli, 50% GC; calf thymus, 42% GC; Clostridium perfringens, 27% GC)
      have been employed as targets of interaction by the cationic polyamines
      spermidine ([H(3)N(CH(2))(3)NH(2)(CH(2))(4)NH(3)](3+)) and spermine
      ([(CH(2))(4)(NH(2)(CH(2))(3)NH(3))(2)](4+)). In solutions containing 60 mM DNA
      phosphate (approximately 20 mg DNA/ml) and either 1, 5 or 60 mM polyamine, only
      Raman bands associated with the phosphates exhibit large spectral changes,
      demonstrating that B-DNA phosphates are the primary targets of interaction.
      Phosphate perturbations, which are independent of base composition, are
      consistent with a model of non-specific cation binding in which delocalized
      polyamines diffuse along DNA while confined by the strong electrostatic potential
      gradient perpendicular to the helix axis. This finding provides experimental
      support for models in which polyamine-induced DNA condensation is driven by non
      specific electrostatic binding. The Raman spectra also demonstrate that major
      groove sites (guanine N7 and thymine C5H(3)) are less affected than phosphates by
      polyamine-DNA interactions. Modest dependence of polyamine binding on genome base
      composition suggests that sequence context plays only a secondary role in
      recognition. Importantly, the results demonstrate that polyamine binding has a
      negligible effect on the native B-form secondary structure. The capability of
      spermidine or spermine to bind and condense genomic B-DNA without disrupting the
      native structure must be taken into account when considering DNA organization
      within bacterial nucleoids or cell nuclei.

PMID- 10954609
TI  - NMR characterization of a kissing complex formed between the TAR RNA element of
      HIV-1 and a DNA aptamer.
AB  - This work presents the first structural analysis of an RNA-DNA complex consisting
      of an 18 nt RNA hairpin and a 20 nt DNA aptamer. The DNA molecule was previously
      selected, from a randomly synthesized library, against the transactivation
      response element (TAR) involved in transcriptional regulation of the HIV genome.
      The DNA aptamer used in the present study is an imperfect stem-loop with the
      sequence 5'-ACTCCCAT-3', characteristic of the selected candidates, in the apical
      loop. This octameric motif contains five bases complementary to the TAR loop
      sequence 5'-CUGGGA-3'. The use of homo- and heteronuclear NMR spectroscopy
      allowed assignment of the complex resonances and resolution of its secondary
      structure. Evidence is given for a kissing complex fold, which consists of a
      quasi-continuous helix formed by one stem of DNA, one stem of RNA and a central
      hybrid helix comprising 5 bp. Two out of helices residues of DNA and one of RNA
      connect the DNA-RNA loop-loop helix to the stem of either partner in the complex.
      In addition, two thymines of the DNA stem are engaged in a non-canonical T.T base
      pair.

PMID- 10954610
TI  - The stress-activated MAP kinase Sty1/Spc1 and a 3'-regulatory element mediate UV
      induced expression of the uvi15(+) gene at the post-transcriptional level.
AB  - Exposure of Schizosaccharomyces pombe cells to UV light results in increased
      uvi15(+) gene expression at both the mRNA and protein levels, leading to elevated
      cell survival. This UV-induced expression of the uvi15(+) gene was reduced in
      Deltasty1 and Deltawis1 cells lacking the stress-activated protein kinase
      pathway, but not in DNA damage checkpoint mutants. To further understand the
      cellular mechanisms responsible for this UV-induced expression, the transcription
      rate and mRNA half-life were investigated. Transcription run-on assays revealed
      that the rate of uvi15(+) transcription was increased 1.8-fold regardless of Sty1
      when cells were UV irradiated. The half-life of uvi15(+) mRNA was also increased
      1.5-fold after UV irradiation, but it was decreased in the Deltasty1 background
      for both basal and UV-induced mRNAs, indicating that the stress-activated MAPK
      cascade can mediate UV-induced gene expression by increasing mRNA half-life.
      Deletion analyses identified a 54 nt element downstream of the distal poly(A)
      site, which was involved in the increased half-life of uvi15(+) mRNA. These
      results suggest that both Sty1 and the 3'-regulatory element regulate UV-induced
      expression of the uvi15(+) gene at the post-transcriptional level.

PMID- 10954612
TI  - Insertion of disease-causing mutations in BACs by homologous recombination in
      Escherichia coli.
AB  - We have used GET Recombination, an inducible homologous recombination system for
      Escherichia coli, to insert one of the most common thalassaemia mutations into
      the intact beta-globin locus in a second generation BAC vector. We first inserted
      a PCR fragment carrying the tetracycline resistance gene (TetR) into the beta
      globin gene. All recombinant clones examined contained the TetR gene at the
      correct target site. Next, a PCR fragment with the IVS I-110 G-->A splicing
      mutation but no selectable marker was used to replace the TetR gene in a second
      round of GET Recombination. Recombinant clones were selected by plating on medium
      containing chlorotetracycline and fusaric acid. Although counterselection for the
      TetR gene is not very efficient, four recombinant colonies with the IVS I-110
      mutation were identified among 480 clones screened. Analysis of the recombinant
      clones did not show any other modifications or rearrangements. Thus the TetR gene
      can be used in combination with GET Recombination to introduce point mutations
      and other modifications in BACs without leaving behind any operational sequences,
      in order to generate accurate cell and transgenic mouse models for various
      diseases.

PMID- 10954613
TI  - An extrachromosomal tetracycline-regulatable system for mammalian cells.
AB  - We have modified the tetracycline-regulatable system so that all components are
      present on a stable extrachromosomal vector that can replicate in a wide variety
      of mammalian cells. An EBV/human ori vector is used to carry the system,
      overcoming the species specificity of conventional Epstein-Barr virus vectors. By
      placing the transcriptional transactivator gene under autoregulation, better
      induction characteristics are obtained. This system offers greater speed and
      sensitivity than previously reported methods. It can be applied within 3-4 weeks
      and produces an induction range of several hundred-fold with a low background.

PMID- 10954611
TI  - REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells.
AB  - The RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor
      (NRSF) can repress transcription of a battery of neuronal differentiation genes
      in non-neuronal cells by binding to a specific consensus DNA sequence present in
      their regulatory regions. However, REST/NRSF(-/-) mice suggest that the absence
      of REST/NRSF-dependent repression alone is not sufficient for the expression of
      these neuronal differentiation genes and that the presence of other
      promoter/enhancer-specific activators is required. Here we describe the
      construction of a recombinant transcription factor, REST-VP16, by replacing
      repressor domains of REST/NRSF with the activation domain of a viral activator
      VP16. In transient transfection experiments, REST-VP16 was found to operate
      through RE1 binding site/neuron-restrictive enhancer element (RE1/NRSE), activate
      plasmid-encoded neuronal promoters in various mammalian cell types and activate
      cellular REST/NRSF target genes, even in the absence of factors that are
      otherwise required to activate such genes. Efficient expression of REST-VP16
      through adenoviral vectors in NT2 cells, which resemble human committed neuronal
      progenitor cells, was found to cause activation of multiple neuronal genes that
      are characteristic markers for neuronal differentiation. Thus, REST-VP16 could be
      used as a unique tool to study neuronal differentiation pathways and neuronal
      diseases that arise due to the deregulation of this process.

PMID- 10954615
TI  - A view on the science: physical anthropology at the millennium.

PMID- 10954614
TI  - Recovery and potential utility of YACs as circular YACs/BACs.
AB  - A method has been established to convert pYAC4-based linear yeast artificial
      chromosomes (YACs) into circular chromosomes that can also be propagated in
      Escherichia coli cells as bacterial artificial chromosomes (BACs). The
      circularization is based on use of a vector that contains a yeast dominant
      selectable marker (G418R), a BAC cassette and short targeting sequences adjacent
      to the edges of the insert in the pYAC4 vector. When it is introduced into yeast,
      the vector recombines with the YAC target sequences to form a circular molecule,
      retaining the insert but discarding most of the sequences of the YAC telomeric
      arms. YACs up to 670 kb can be efficiently circularized using this vector. Re
      isolation of megabase-size YAC inserts as a set of overlapping circular YAC/BACs,
      based on the use of an Alu-containing targeting vector, is also described. We
      have shown that circular DNA molecules up to 250 kb can be efficiently and
      accurately transferred into E.coli cells by electroporation. Larger circular DNAs
      cannot be moved into bacterial cells, but can be purified away from linear yeast
      chromosomes. We propose that the described system for generation of circular YAC
      derivatives can facilitate sequencing as well as functional analysis of genomic
      regions.

PMID- 10954616
TI  - Genetic structure of Quechua-speakers of the Central Andes and geographic
      patterns of gene frequencies in South Amerindian populations.
AB  - A sample of 141 Quechua-speaking individuals of the population of Tayacaja, in
      the Peruvian Central Andes, was typed for the following 16 genetic systems: ABO,
      Rh, MNSs, P, Duffy, AcP1, EsD, GLOI, PGM1, AK, 6-PGD, Hp, Gc, Pi, C3, and Bf. The
      genetic structure of the population was analyzed in relation to the allele
      frequencies available for other South Amerindian populations, using a combination
      of multivariate and multivariable techniques. Spatial autocorrelation analysis
      was performed independently for 13 alleles to identify patterns of gene flow in
      South America as a whole and in more specific geographic regions. We found a
      longitudinal cline for the AcP1*a and EsD*1 alleles which we interpreted as the
      result of an ancient longitudinal expansion of a putative ancestral population of
      modern Amerindians. Monmonnier's algorithm, used to identify areas of sharp
      genetic discontinuity, suggested a clear east-west differentiation of native
      South American populations, which was confirmed by analysis of the distribution
      of genetic distances. We suggest that this pattern of genetic structures is the
      consequence of the independent peopling of western and eastern South America or
      to low levels of gene flow between these regions, related to different
      environmental and demographic histories.

PMID- 10954617
TI  - Mitochondrial DNA polymorphisms in Chilean aboriginal populations: implications
      for the peopling of the southern cone of the continent.
AB  - The mitochondrial DNAs (mtDNAs) from individuals belonging to three Chilean
      tribes, the Mapuche, the Pehuenche, and the Yaghan, were studied both by RFLP
      analysis and D-loop (control region) sequencing. RFLP analysis showed that 3
      individuals (1.3%) belonged to haplogroup A, 19 (8%) to haplogroup B, 102 (43%)
      to haplogroup C, and 113 (47.7%) to haplogroup D. Among the 73 individuals
      analyzed by D-loop sequencing, we observed 37 different haplotypes defined by 52
      polymorphic sites. Joint analysis of data obtained by RFLP and sequencing methods
      demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of
      these three contemporary South American aborigine groups clustered into four main
      haplogroups, in a way similar to those previously described for other
      Amerindians. These results further revealed the absence of haplogroup A in both
      the Mapuche and Yaghan as well as the absence of haplogroup B in the Yaghan.
      These results suggest that the people of Tierra del Fuego are related to tribes
      from south-central South America.

PMID- 10954618
TI  - Pregnancy outcome for nomadic Turkana pastoralists of Kenya.
AB  - The outcome of an individual pregnancy is a key component of overall reproductive
      success and is strongly influenced by environmental, behavioral, and biological
      variation within populations. This prospective study examined the outcomes of 68
      pregnancies among nomadic Turkana of Kenya from July 1993 to July 1994. A total
      of 12 women experienced pregnancy losses, and 3 women experienced live births
      with a subsequent perinatal death. The following characteristics are associated
      with increased risk for experiencing a fetal or perinatal death: severe morbidity
      episodes, shorter nonpregnant intervals, lower third-trimester weight, higher
      third-trimester summed skinfolds but limited third-trimester reduction in summed
      skinfolds, and higher activity levels late in gestation. Turkana newborns
      measured within 48 hr of birth (n = 19) weighed an average of 2,860 +/- 640 g and
      had a mean ponderal index of 2.72 +/- 0.46. Variation in birth weight was
      predicted by preterm delivery, delivery during the wet season, and maternal
      morbidity levels. Birth length averaged 50.8 +/- 6.8 cm and was positively
      influenced by full term delivery, better maternal health, and birth during the
      dry season. These results suggest complicated pathways linking the physical
      environment, subsistence requirements, heterogeneity in maternal fitness,
      behavior, and pregnancy outcome. The results augment the larger picture of
      reproductive success for Turkana nomads who live in a highly variable savanna
      environment.

PMID- 10954619
TI  - Lung volume, chest size, and hematological variation in low-, medium-, and high
      altitude central Asian populations.
AB  - To evaluate adaptive responses to high-altitude environment, we examined three
      groups of healthy adult males from Central Asia: 94 high-altitude (HA) Kirghiz
      subjects (3,200 m above sea level); 114 middle-altitude (MA) Kazakh subjects
      (2,100 m), and 90 low-altitude (LA) Kirghiz subjects (900 m). Data on chest size
      (chest perimeter and chest diameter), lung volume (forced expiratory volume (FEV)
      and forced expiratory volume in 1 sec (FEV1)), and hematological parameters
      (hemoglobin, erythrocytes, hematocrit, and SaO(2)) are discussed. The results
      show that 1) chest shape is less flat in the samples living at higher altitude.
      In the HA sample, chest perimeter is lower but chest excursion is high. 2) In the
      highlanders, forced vital capacity (FVC) and FEV1 are no higher than in the other
      samples, even when corrected for stature and body weight. The negative
      correlation between FVC-FEV1 and age decreases with increasing altitude. 3) The
      HA and MA samples have higher values of hemoglobin, erythrocytes, and hematocrit.
      The HA sample has lower SaO(2) and higher arterial oxygen content than the LA
      sample. No association between hematocrit and age was detected in the four
      samples. The results indicate that the high-altitude Kirghiz present features of
      developmental acclimatization to hypobaric hypoxia which are also strongly
      influenced by other major high-altitude environmental stresses.

PMID- 10954620
TI  - Body mass in lowland gorillas: a quantitative analysis.
AB  - Body proportions and tissue composition (e.g., relative contributions of muscle,
      skin, bone, and adipose to total body mass) were determined through dissection of
      four adult captive lowland gorillas. The relative contribution of bone varies
      little among the four animals (10.2-13.4%) despite considerable range in body
      weights (99.5-211 kg). In tissue composition, three animals have on average 37.3%
      muscle relative to body mass. Maximum estimates of body fat range between 19.4
      44%. Differences in age, sex, and life history events partially explain the
      observed variation in body proportions and tissue composition among the four
      animals. Although gorillas are considered extremely sexually dimorphic in body
      weight and canine size, differences in tissue are not as dramatic as body mass
      differences suggest. This study found sex differences mostly in the upper body;
      males have relatively heavier forelimbs, including heavier deltoid, trunk
      binding, and deep back muscles compared to the younger female. The old, obese
      female had one half the muscle tissue of the other three animals (16% vs. 37.3%),
      and twice the body fat (44%); forelimbs and upper body musculature were
      relatively well-developed to compensate for the restricted hip-joint movement due
      to arthritis. Data on the variation in tissue composition and body proportions in
      gorillas provide a basis for comparison with other hominoids, including humans.
      For example, compared to highly dimorphic orangutans, gorillas have more muscle,
      less adipose tissue, lighter forelimbs and heavier hindlimbs. Such analyses
      complement studies of the skeleton and contribute to our understanding of human
      evolution and adaptation.

PMID- 10954621
TI  - On statistical methods for comparison of intrasample morphometric variability:
      Zalavar revisited.
AB  - In studies of morphology, methods for comparing amounts of variability are often
      important. Three different ways of utilizing determinants of covariance matrices
      for testing for surplus variability in a hypothesis sample compared to a
      reference sample are presented: an F-test based on standardized generalized
      variances, a parametric bootstrap based on draws on Wishart matrices, and a
      nonparametric bootstrap. The F-test based on standardized generalized variances
      and the Wishart-based bootstrap are applicable when multivariate normality can be
      assumed. These methods can be applied with only summary data available. However,
      the nonparametric bootstrap can be applied with multivariate nonnormally
      distributed data as well as multivariate normally distributed data, and small
      sample sizes. Therefore, this method is preferable when raw data are available.
      Three craniometric samples are used to present the methods. A Hungarian Zalavar
      sample and an Austrian Berg sample are compared to a Norwegian Oslo sample, the
      latter employed as reference sample. In agreement with a previous study, it is
      shown that the Zalavar sample does not represent surplus variability, whereas the
      Berg sample does represent such a surplus variability.

PMID- 10954622
TI  - Context of maternal lineages in the Greater Southwest.
AB  - We present mitochondrial haplogroup characterizations of the prehistoric Anasazi
      of the United States (US) Southwest. These data are part of a long-term project
      to characterize ancient Great Basin and US Southwest samples for mitochondrial
      DNA (mtDNA) diversity. Three restriction site polymorphisms (RSPs) and one length
      polymorphism identify four common Native American matrilines (A, B, C, and D).
      The Anasazi (n = 27) are shown to have a moderate frequency of haplogroup A
      (22%), a high frequency of haplogroup B (56%), and a low frequency of C (15%).
      Haplogroup D has not yet been detected among the Anasazi. In comparison to modern
      Native American groups from the US Southwest, the Anasazi are shown to have a
      distribution of haplogroups similar to the frequency pattern exhibited by modern
      Pueblo groups. A principal component analysis also clusters the Anasazi with some
      modern (Pueblo) Southwestern populations, and away from other modern (Athapaskan
      speaking) Southwestern populations. The Anasazi are also shown to have a
      significantly different distribution of the four haplogroups as compared to the
      eastern Great Basin Great Salt Lake Fremont (n = 32), although both groups
      cluster together in a principal component analysis. The context of our data
      suggests substantial stability within the US Southwest, even in the face of the
      serious cultural and biological disruption caused by colonization of the region
      by European settlers. We conclude that although sample numbers are fairly low,
      ancient DNA (aDNA) data are useful for assessing long-term populational
      affinities and for discerning regional population structure.

PMID- 10954623
TI  - Humerus varus deformity in Roman period burials from Kellis 2, Dakhleh, Egypt.
AB  - Humerus varus deformity (HVD) occurs unilaterally in a female (#85) skeleton and
      bilaterally in a male (#124) from Kellis 2, a Roman period cemetery (circa 300
      450 AD) from Dakhleh, Egypt. The affected humeri were shortened, their
      glenohumeral joints deformed, and their upper diaphyses were angulated. The
      skeletons were otherwise normal. The severity of the changes suggests that the
      underlying growth disturbances occurred early in postnatal development. The
      differential diagnosis considers the mucopolysaccharidoses, thalassemia,
      infection, and birth trauma, with the latter being favored. Clinical data show
      limited morbidity or functional impairment in individuals with HVD, although
      radiographic analysis suggests that #85 may have favored her dominant arm. Ortner
      and Putschar (1981), and Hershkovitz et al (1991) describe the only other
      archaeological cases of HVD. These authors provide useful, though limited,
      information on the differential diagnosis of HVD in archaeological specimens.
      Future research should focus on documenting the prevalence and expressivity of
      HVD in Mediterranean population samples where thalassemia evolved. HVD is
      relatively common in thalassemics and this approach would be valuable for
      documenting the range of osseous responses characteristic of HVD.

PMID- 10954624
TI  - Endocranial capacity of the bodo cranium determined from three-dimensional
      computed tomography.
AB  - The 600,000-year-old cranium from Bodo, Ethiopia, is the oldest and most complete
      early Middle Pleistocene hominid skull from Africa. "Virtual endocast" models
      created by three-dimensional computed tomography (CT) techniques indicate an
      endocranial capacity of about 1,250 cc for this cranium (with a reasonable range
      between approximately 1,200-1,325 cc, depending on how missing portions of the
      basicranial region are reconstructed). From these determinations, several
      important implications emerge concerning current interpretations of "tempo and
      mode" in early hominid brain evolution: 1) already by the early Middle
      Pleistocene, at least one African hominid species, Homo heidelbergensis, had
      reached an endocranial capacity within the normal range of modern humans; 2) in
      spite of its large endocranial capacity, estimates of Bodo's encephalization
      quotient fall below those found in a large sample of Homo sapiens (both fossil
      and recent) and Neandertals; and 3) the greatest burst of brain expansion in the
      Homo lineage may not have been in the last several hundred thousand years, but
      rather much earlier in the Lower to early Middle Pleistocene.

PMID- 10954625
TI  - Lactose digestion capacity in Tokelauans: a case for the role of gene flow and
      genetic drift in establishing the lactose absorption allele in a Polynesian
      population.
AB  - Throughout the Pacific, lactose absorption occurs at rates of 0-46%. Most authors
      explain the current rate of lactose absorption in the Pacific in terms of gene
      flow with Europeans. However, researchers have not been able to determine the
      exact historical circumstances of the introduction of the lactose absorption
      gene. The availability of genealogical material, historical information, and
      mal/absorption frequencies for Tokelau (a Polynesian population) presents a
      unique opportunity to examine the role of gene flow in establishing lactose
      absorption in Pacific isolates. In an earlier study, Cheer and Allen ([1997] Am.
      J. Hum. Biol. 93:1-34) determined lactose digestion capacities for 58 Tokelauans.
      In the current study, we constructed pedigrees for the same 58 individuals, using
      the Tokelau Island Migrant Study genealogies (Wessen et al. [1992]). Results
      indicated that 8 of 13 lactose-absorbing individuals have European ancestors,
      compared with only 4 of 35 lactose malabsorbers (Chi(2) = 15.75, P < 0.01). Six
      lactose-absorbing individuals have either American or Portuguese ancestors dating
      back to the mid-1800s. Historical data were used to establish the contribution of
      Portuguese and American genetic material to the Tokelau population following
      massive depopulation after the Peruvian slave raids of 1863. This study provides
      clear evidence for the role of a population bottleneck followed by gene flow and
      genetic drift in establishing lactose absorption in the Tokelau population.
      Furthermore, it is the first study of a Pacific population to directly link
      lactose absorption with gene flow.

PMID- 10954626
TI  - Brief communication: discouraging prospects for ancient DNA from India.

PMID- 10954627
TI  - Brief communication: the timing of linear hypoplasias on human anterior teeth.
AB  - One hundred and fifteen unworn anterior teeth were sectioned longitudinally with
      a diamond saw and prepared for histological examination by polarized light
      microscopy. Incremental markings in the enamel of each tooth were used to
      estimate the average total crown formation times of each tooth type. The total
      time taken to form the crowns of each tooth type was apportioned by 1) cuspal
      enamel formation and 2) each tenth percentile of total tooth height. Based on
      these data, and on histological estimates for the time of initiation of
      mineralization in each anterior tooth, the following conclusions can be drawn.
      Little if any visible surface enamel is likely to form before the end of the
      first year after birth in any anterior tooth type. No relation exists between
      tooth crown height and the total time taken to form enamel. Anterior crown
      formation is nonlinear and slows towards the cervix in all teeth. The estimated
      mean chronological age at crown completion ranged in this study from between
      around 4 years for lower central incisors to around 6 years for lower canines. We
      suggest that these combined findings will be useful for devising more reliable
      ways to estimate the timing of linear enamel hypoplasias than some methods
      currently in use.

PMID- 10954628
TI  - Primary superficial bladder cancer risk groups according to progression,
      mortality and recurrence.
AB  - PURPOSE: We identified risk groups in primary superficial bladder cancer
      according to progression, mortality and recurrence rates. MATERIALS AND METHODS:
      The prognostic factors of progression, mortality and recurrence were identified
      by multivariate analysis in a cohort of 1,529 patients with primary superficial
      bladder cancer. Risk groups were designed by combining the relative risk of these
      prognostic factors. We performed survival analysis of progression, tumor
      mortality and recurrence by risk group using the Kaplan-Meier method. Relative
      risk in each group was calculated by Cox regression. We present timetables of
      progression, mortality and recurrence by risk group. RESULTS: Risk groups were
      classified as low-grade 1 stage Ta disease and a single grade 1 stage T1 tumor,
      intermediate-multiple grade 1 stage T1 tumors, grade 2 stage Ta disease and a
      single grade 2 stage T1 tumor, and high-multiple grade 2 stage T1 tumors, grade 3
      stages Ta and T1 disease, and any stage disease associated with carcinoma in
      situ. Survival analysis of progression, mortality and recurrence revealed a
      statistically significant difference among the 3 risk groups. The rates of
      recurrence, progression and mortality were 37%, 0% and 0% in the low, 45%, 1.8%
      and 0.73% in the intermediate, and 54%, 15% and 9.5% in the high risk group,
      respectively. The relative risks of recurrence, progression and mortality in the
      low versus the intermediate and high risk groups were 1.37, 2.84 and 1, and 1.87,
      24.76 and 14.69, respectively. CONCLUSIONS: Risk group classification based on
      prognostic factors defines progression, mortality and recurrence rates in primary
      superficial bladder cancer. It may be useful for designing treatment and followup
      strategies.

PMID- 10954629
TI  - Anatomic and biomechanical analysis of the lower lumbar foraminal ligaments.
AB  - STUDY DESIGN: An anatomic cadaveric study to characterize the lumbar
      intraforaminal nerve root attachments. OBJECTIVES: To characterize the
      intraforaminal nerve root attachments and describe their anatomic relationships
      and biomechanical properties. SUMMARY OF BACKGROUND DATA: Observations during
      foraminotomies for lateral recess stenosis as well as lateral approaches for far
      lateral disc herniation have shown dense attachments between the nerve root and
      adjacent structures. Little or no information has appeared in the literature
      describing intraforaminal nerve root attachments. METHODS: Twelve fresh-frozen
      human cadaveric lumbar spines were used to study intraforaminal ligamentous
      structures. Four cadavers were cut into sagittal sections for qualitative
      description, and eight were used for biomechanical testing. Histologic analyses
      were performed on samples of the foraminal attachments to assure that they were
      not vascular or neural structures. Biomechanical testing of the nerve roots with
      ligamentous attachments was performed measuring load to failure along the
      anatomic axis of the root. RESULTS: The dissections showed four distinct bands
      extending radially from the nerve root sleeve. The most prominent nerve root
      attachment was to the facet capsule posteriorly. Other ligaments fanned out with
      attachments inferiorly and superiorly to the adjacent pedicles and anteriorly to
      the intervertebral disc. Biomechanical study of the L3, L4, and L5 nerve roots
      showed a significant increase in strength at failure with axial traction,
      progressing from L3 to L5. CONCLUSIONS: The results demonstrate that these
      foraminal ligaments are normal anatomic structures within the intervertebral
      foramen of the lumbar spine. In addition, they may play a role in limiting motion
      along the nerve root.

PMID- 10954630
TI  - Sensory innervation of the sacroiliac joint in rats.
AB  - STUDY DESIGN: The segmental levels of dorsal root ganglions innervating the
      sacroiliac joint in rats were investigated using the retrograde transport method.
      The pathways and functions of the nerve fibers supplying the sacroiliac joint
      were determined by immunohistochemical detection of transported tracer.
      OBJECTIVES: To study the sensory innervation of the sacroiliac joint and to
      elucidate the neural pathways of low back pain originating from the sacroiliac
      joint. SUMMARY OF BACKGROUND DATA: The sacroiliac joint is a possible source of
      low back pain. The L4-S4 spinal nerves have been regarded as the nerves
      innervating the sacroiliac joint in humans. However, the origins of nerve fibers
      have not been analyzed experimentally with tracer methods. METHODS: Cholera toxin
      B subunit, a neural tracer, was injected into the left sacroiliac joint of adult
      rats, and the bilateral dorsal root ganglions were immunohistochemically examined
      4 days after injection. In another rat group, the dorsal root ganglions were
      examined using the same methods after resection of the left sympathetic trunk
      from L2 to the most caudal level. Thus, the pathways of the nerve fibers
      supplying the sacroiliac joint were investigated. RESULTS: Labeled neurons were
      mainly located in the ipsilateral dorsal root ganglions from L1 to S2 of the
      unsympathectomized rats and in the ipsilateral dorsal root ganglions from L4 to
      S2 of the sympathectomized rats. CONCLUSIONS: The sacroiliac joint was innervated
      by sensory neurons in dorsal root ganglions ipsilateral to the joint from L1 to
      S2. Sensory fibers from the L1 and L2 dorsal root ganglions passed through the
      paravertebral sympathetic trunk.

PMID- 10954631
TI  - Motion in lumbar functional spine units during side bending and axial rotation
      moments depending on the degree of degeneration.
AB  - STUDY DESIGN: Human lumbar spine specimens were tested in axial rotation and side
      bending. Motion was related to the grade of degeneration. OBJECTIVES: To
      determine the degree to which degeneration with fissure formation in the disc
      affects axial rotation of the lumbar functional spine unit. SUMMARY OF BACKGROUND
      DATA: There is controversy in the literature regarding the influence of severe
      degeneration and fissures of the disc on the range of axial rotation. METHODS:
      Thirty-six lumbar spine specimens were tested in axial rotation and side bending,
      by applying pure moments in an unconstrained setting. The motion in 6 df was
      recorded by dial gauges. The grade of degeneration was established by the grading
      schemes of Nachemson, Thompson, Adams, and Mimura. RESULTS: A significant
      increase of axial rotation and lateral translation under torque was found. This
      increase mainly took place between Grade 3 according to the schemes of Nachemson,
      Thompson, and Adams (no fissure formation) and the higher grades of degeneration
      (defined by fissure formation). Reduced disc height was always associated with
      fissures. CONCLUSIONS: A reduced lumbar disc height in radiographs seems to be
      associated with fissure formation in the disc. In this case, the range axial
      rotation after torque is increased in comparison with cases with less
      degeneration.

PMID- 10954632
TI  - Anterior fusion for rotationally unstable cervical spine fractures.
AB  - STUDY DESIGN: A retrospective analysis of 32 rotationally unstable cervical
      fractures treated by brace, halo vest, or posterior surgical constructs plus
      fusion is compared with a second, prospective study of 18 similar fractures
      treated by early anterior discectomy, fusion, and plating. OBJECTIVES: To
      characterize an often unrecognized fracture pattern and compare various methods
      of management to identify the most effective treatment. SUMMARY OF BACKGROUND
      DATA: The rotationally unstable cervical spine fracture (compression-extension
      Stage 1) involves a hyperextension and lateral flexion injury, resulting in a
      unilateral pedicle, facet complex, and/or lamina fracture under compression and
      anterior annular disruption under tension. This fracture pattern allows a
      rotatory spondylolisthesis of the spine around the axis of the intact lateral
      mass and facet complex. METHODS: A retrospective review was made of 284 cervical
      fractures, identifying 32 compression-extension Stage 1 fractures that were
      treated by a variety of techniques. The results of that study led to a second
      (prospective) study, in which 18 similar fractures were treated by early anterior
      discectomy, fusion, and plating. RESULTS: Nonoperative treatment was uniformly
      unsuccessful. Posterior stabilization and fusion procedures led to unsuccessful
      results in 45%, related either to late kyphosis because of disc collapse or the
      inability of midline stabilization procedures to control rotational instability.
      Anterior fusion resulted in solid union without residual deformity in all cases.
      All four patients in the prospective study with incomplete cord lesions showed
      improvement in cord function, as did seven patients who had radiculopathy.
      CONCLUSION: Although posterior bony injury is the usual radiographic finding, the
      anterior disc and anterior longitudinal ligament disruption are the more
      significant injuries and lead to late collapse and kyphotic deformity. Early
      anterior fusion is recommended in compression- extension Stage 1 cervical spine
      injuries.

PMID- 10954633
TI  - Management of cervical spinal fractures in ankylosing spondylitis with posterior
      fixation.
AB  - STUDY DESIGN: Introduction of a posterior approach for internal fixation of
      fractures of the ankylosed cervical spine. OBJECTIVES: To evaluate the clinical
      outcome of patients with ankylosing spondylitis and cervical spinal fractures
      treated with posterior instrumentation and a collar orthosis. SUMMARY OF
      BACKGROUND DATA: Cervical spinal fractures in patients with ankylosing
      spondylitis almost always extend completely across the vertebral segment to
      include both anterior and posterior elements. Treatment with immobilization alone
      is often inadequate. Generalized spinal rigidity and exaggerated thoracic
      kyphosis may hinder anterior exposure. Posterior approaches have been described
      but generally require postoperative halo immobilization. In the authors'
      technique for patients whose spinal alignment is relatively well preserved, a
      posterior exposure is used that achieves three-point internal fixation along
      multiple segments. The complications associated with halo immobilization are
      avoided. METHODS: Seven patients with ankylosing spondylitis and fractures of the
      cervical spine were stabilized with posterior instrumentation. Patients were
      immobilized after surgery with either a cervical collar or a sternal occipital
      mandibular immobilizing brace and observed for neurologic outcome, radiographic
      evidence of bony fusion, and complications. RESULTS: No patient experienced
      neurologic deterioration with surgery. Two patients died at acute rehabilitative
      facilities after discharge. Radiographic evidence of fusion was observed in the
      five patients available for follow-up. CONCLUSIONS: Patients with ankylosing
      spondylitis and cervical spinal fractures can be adequately treated with lateral
      mass plating and interspinous wiring of autologous rib graft. Adequate
      postoperative immobilization can be attained with a cervical collar and does not
      require a halo vest.

PMID- 10954634
TI  - Three- and four-level anterior cervical discectomy and fusion with plate
      fixation: a prospective study.
AB  - STUDY DESIGN: A prospective study of 15 patients who underwent modified Smith
      Robinson anterior cervical discectomy and fusion at three or four operative
      levels stabilized with an unicortical anterior plate. OBJECTIVES: To provide
      medium-term follow-up data on the surgical success and patient outcome of three-
      and four-level anterior cervical discectomies and fusions and to determine the
      effect that plate fixation has on the results. SUMMARY OF BACKGROUND DATA: The
      success of arthrodesis for anterior cervical fusion depends on several factors,
      including the number of surgical levels. The arthrodesis rate and outcome for
      patients having three- and four-level discectomy and fusion procedures is
      disappointing. Internal fixation putatively improves these parameters. METHODS:
      Fifteen patients (average age, 51 years; range, 35-77), were observed for an
      average of 42 months (range, 25-73) All had an anterior discectomy, burring of
      the endplates, placement of an autogenous tricortical iliac crest graft at three
      (12 patients) or four (3 patients) levels, and application of a Cervical Spine
      Locking Plate. All patients had follow-up office visits with examinations and
      radiographs. Radiographic union, postoperative pain relief, and neurologic
      recovery were evaluated. RESULTS: Solid arthrodesis was achieved at all levels in
      only 7 (47%) of the 15 patients after a single procedure. Of the 8 patients with
      pseudarthrosis, 3 had sufficient pain to necessitate revision surgery (with pain
      relief in two), 1 had pain without further surgery, and 4 no pain. Of the 7 with
      solid fusion, 3 had persistent pain, and 4 had none. Two in this group had a
      second procedure. All 4 patients with preoperative myelopathy improved, and 10 of
      the 11 with radiculopathy had resolution of arm symptoms. CONCLUSIONS: Three- and
      four-level modified Robinson cervical discectomy and fusion results in an
      unacceptably high rate of pseudarthrosis. The Cervical Spine Locking Plate alone
      does not appear to improve the arthrodesis rate.

PMID- 10954635
TI  - Computed tomographic findings in patients with persistent sacroiliac pain after
      posterior iliac graft harvesting.
AB  - STUDY DESIGN: A retrospective study of 24 sacroiliac joint computed tomographic
      (CT) scans of patients with persistent donor site pain. OBJECTIVE: To illustrate
      the computed tomographic findings of sacroiliac joints in patients who underwent
      posterior iliac bone graft harvesting with subsequent persistent donor site pain.
      SUMMARY OF BACKGROUND DATA: In a previous study the posterior iliac bone
      harvesting site was divided into three zones. Zone 1 carried no risk of violation
      of the synovial part of the sacroiliac joint. In Zones 2 and 3 there was a
      potential risk of violation to the synovial part of the sacroiliac joint. There
      is no study in the literature on the effect of violating the different parts of
      the sacroiliac joint during posterior iliac bone graft harvesting. METHODS:
      Computed tomographic scans of the sacroiliac joints of 22 patients with
      persistent pain in 24 sacroiliac joints after posterior iliac bone graft
      harvesting were retrospectively reviewed. RESULTS: Of the 16 sacroiliac joints
      with evidence of disruption of the inner table at the ligamentous part, 10 showed
      mild degenerative changes, and 6 showed moderate changes. Three joints with
      evidence of disruption of the inner table at the synovial part showed severe
      degenerative changes. Five joints with no evidence of inner table disruption did
      not show degenerative changes. CONCLUSION: There is a high prevalence of inner
      table disruption in patients with persistent sacroiliac joint pain after
      posterior iliac bone graft harvesting. The computed tomographic scan showed that
      involvement of the synovial part caused more severe degenerative changes than
      involvement of the ligamentous part.

PMID- 10954636
TI  - Breast cancer mortality after diagnostic radiography: findings from the U.S.
      Scoliosis Cohort Study.
AB  - STUDY DESIGN: A retrospective cohort study was conducted in 5573 female patients
      with scoliosis who were referred for treatment at 14 orthopedic medical centers
      in the United States. Patients were less than 20 years of age at diagnosis which
      occurred between 1912 and 1965. OBJECTIVES: To evaluate patterns in breast cancer
      mortality among women with scoliosis, with special emphasis on risk associated
      with diagnostic radiograph exposures. SUMMARY OF BACKGROUND DATA: A pilot study
      of 1030 women with scoliosis revealed a nearly twofold statistically significant
      increased risk for incident breast cancer. Although based on only 11 cases,
      findings were consistent with radiation as a causative factor. METHODS: Medical
      records were reviewed for information on personal characteristics and scoliosis
      history. Diagnostic radiograph exposures were tabulated based on review of
      radiographs, radiology reports in the medical records, radiograph jackets, and
      radiology log books. Radiation doses were estimated for individual examinations.
      The mortality rate of the cohort through January 1, 1997, was determined by using
      state and national vital statistics records and was compared with that of women
      in the general U. S. population. RESULTS: Nearly 138,000 radiographic
      examinations were recorded. The average number of examinations per patient was
      24.7 (range, 0-618); mean estimated cumulative radiation dose to the breast was
      10.8 cGy (range, 0-170). After excluding patients with missing information, 5466
      patients were included in breast cancer mortality analyses. Their mean age at
      diagnosis was 10.6 years and average length of follow-up was 40.1 years. There
      were 77 breast cancer deaths observed compared with the 45.6 deaths expected on
      the basis of U.S. mortality rates (standardized mortality ratio [SMR] = 1.69; 95%
      confidence interval [CI] = 1.3-2.1). Risk increased significantly with increasing
      number of radiograph exposures and with cumulative radiation dose. The unadjusted
      excess relative risk per Gy was 5.4 (95% CI = 1.2-14.1); when analyses were
      restricted to patients who had undergone at least one radiographic examination,
      the risk estimate was 2.7 (95% CI = -0. 2-9.3). CONCLUSIONS: These data suggest
      that exposure to multiple diagnostic radiographic examinations during childhood
      and adolescence may increase the risk of breast cancer among women with
      scoliosis; however, potential confounding between radiation dose and severity of
      disease and thus with reproductive history may explain some of the increased risk
      observed.

PMID- 10954637
TI  - Effects of thoracolumbosacral orthosis on spinal deformities, trunk asymmetry,
      and frontal lower rib cage in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Prospective study. OBJECTIVES: To document immediate and late
      changes in shape and balance of the thoracic and lumbar spine and lower rib cage
      on the frontal plane induced by treatment with a thoracolumbosacral orthosis
      (TLSO). SUMMARY OF BACKGROUND DATA: The effect of TLSO on lateral plane of spinal
      deformity, frontal lower rib cage, trunk balance, and natural history are poorly
      understood. METHODS: Twenty-four female adolescents with major thoracic and/or
      lumbar scoliosis, averaging 30 degrees and 26 degrees, respectively, were treated
      with a full-time TLSO program. Scoliosis, kyphosis, convex, and concave rib
      vertebral angles T7 to T12, frontal trunk balance, frontal vertebral inclination,
      rotation and translation from T7 to L4-vertebrae were measured before bracing, 1
      month after bracing, and biannually thereafter in brace and without brace for a 4
      year period and reevaluated at the age of 20 years, at an average of 3.5 years
      after termination of bracing to measure any permanent changes. RESULTS:
      Thoracolumbosacral orthosis treatment corrected both thoracic and lumbar
      scoliosis and reduced lateral trunk shift at the expense of significant, although
      temporary reduced physiological thoracic kyphosis, increased lateral displacement
      of T7 to T10, increased frontal inclination of L2 to L4, and elevation of the
      apical concave rib in favor of reduction of lateral displacement of T11 to L4;
      decreased frontal inclination of T7, T9, and T11; and derotated L1 and L2 and
      thoracic apical vertebra without affecting drooping of the 7th to 12th ribs. In
      this series, there was marked inconsistency in the obtained changes in several of
      the roentgenographic parameters in the different evaluations, which is probably
      because of the empiric application of the TLSO during different periods of
      treatment. 3.5 years after termination of TLSO-wearing, all roentgenographic
      parameters remained to the prebrace values. CONCLUSIONS: Thoracolumbosacral
      orthosis program maintained the measured roentgenographic parameters at the
      prebrace levels in progressive adolescent idiopathic scoliosis, but it had no
      effect on the droop of the seven lower ribs. The TLSO treatment stopped
      progression of scoliosis and reduced the number of patients requiring surgery.
      Thus, it changed the natural history of scoliosis.

PMID- 10954638
TI  - Cobb method or Harrison posterior tangent method: which to choose for lateral
      cervical radiographic analysis.
AB  - STUDY DESIGN: Thirty lateral cervical radiographs were digitized twice by three
      examiners to compare reliability of the Cobb and posterior tangent methods.
      OBJECTIVES: To determine the reliability of the Cobb and Harrison posterior
      tangent methods and to compare and contrast these two methods. SUMMARY OF
      BACKGROUND DATA: Cobb's method is commonly used on both anteroposterior and
      lateral radiographs, whereas the posterior tangent method is not widely used.
      METHODS: A blind, repeated-measures design was used. Thirty lateral cervical
      radiographs were digitized twice by each of three examiners. To evaluate
      reliability of determining global and segmental alignment, vertebral bodies of C1
      T1 were digitized. Angles created were two global two-line Cobb angles (C1-C7 and
      C2-C7), segmental Cobb angles from C2 to C7, and posterior tangents drawn at each
      posterior vertebral body margin. Cobb's method and the posterior tangent method
      are compared and contrasted with these data. RESULTS: Of 34 intraclass and
      interclass correlation coefficients, 28 were in the high range (>0.7), and 6 were
      in the good range (0.6-0.7). The Cobb method at C1-C7 overestimated the cervical
      curvature (-54 degrees ) and, at C2-C7 it underestimated the cervical curve (-17
      degrees ), whereas the posterior tangents were the slopes along the curve (-26
      degrees from C2 to C7). The inferior vertebral endplates and posterior body
      margins did not meet at 90 degrees (C2: 105 degrees +/- 5.2 degrees, C3: 99.7
      degrees +/- 5.2 degrees, C4: 99.9 degrees +/- 5.8 degrees, C5: 96.1 degrees +/-
      4.5 degrees, C6: 97.0 degrees +/- 3.8 degrees, C7: 95.4 degrees +/- 4.1 degrees
      ), which caused the segmental Cobb angles to underestimate lordosis at C2-C3, C4
      C5, and C6-C7. CONCLUSIONS: Although both methods are reliable with the majority
      of correlation coefficients in the high range (ICC > 0.7), from the literature,
      the posterior tangent method has a smaller standard error of measurement than
      four-line Cobb methods. Global Cobb angles compare only the ends of the cervical
      curve and cannot delineate what happens to the curve internally. Posterior
      tangents are the slopes along the curve and can provide an analysis of any
      buckled areas of the cervical curve. The posterior tangent method is part of an
      engineering analysis (first derivative) and more accurately depicts cervical
      curvature than the Cobb method.

PMID- 10954639
TI  - Reliability of magnetic resonance imaging in detecting posterior ligament complex
      injury in thoracolumbar spinal fractures.
AB  - STUDY DESIGN: Prospective study of 34 patients with thoracolumbar spinal
      fractures. OBJECTIVES: To assess the reliability of magnetic resonance imaging
      (MRI) for posterior ligament complex injury in thoracolumbar spinal fractures.
      SUMMARY OF BACKGROUND DATA: Some researchers have studied posterior ligament
      complex injury in spinal fracture using MRI. However, most did not evaluate the
      findings of MRI compared with the operative findings. METHODS: Thirty-four
      patients with thoracolumbar spinal fracture were evaluated by palpation of the
      interspinous gap, plain radiography, and MRI before operation. In addition to
      conventional MRI sequences, a fat-suppressed T2-weighted sagittal sequence was
      performed. Surgery was performed by a posterior approach. During the operation,
      posterior ligament complex injury was carefully examined. RESULTS: A wide
      interspinous gap was palpated in 14 patients and was found in 21 patients on
      plain radiography. Magnetic resonance imaging raised suspicion of injury to the
      posterior ligament complex in 30 patients. According to interpretation of MRI,
      injury to the supraspinous ligament was suspected in 27 patients, the
      interspinous ligament in 30 patients, and the ligamentum flavum in 9 patients.
      There were 28 supraspinous ligament injuries, 29 interspinous ligament injuries,
      and 7 ligamentum flavum injuries in operative findings. There was a significant
      relation between MRI interpretation and operative findings. CONCLUSION: A fat
      suppressed T2-weighted sagittal sequence of MRI was a highly sensitive, specific,
      and accurate method of evaluating posterior ligament complex injury. Based on the
      results of this study, a fat-suppressed T2-weighted sagittal sequence of MRIs is
      recommended for the accurate evaluation of posterior ligament complex injury and
      would be helpful in the selection of treatment options.

PMID- 10954640
TI  - A prospective follow-up study of low back pain in the community.
AB  - STUDY DESIGN: Opportunistic prospective follow-up study. OBJECTIVE: To describe
      the natural history of low back pain in the community and to model the factors
      predictive of recovered versus persistent low back pain. SUMMARY OF BACKGROUND
      DATA: A two-phase questionnaire was mailed to adults in the Bradford Metropolitan
      Health District in 1994. Valid respondents were surveyed again in 1997. Analysis
      is based on the combined results of these two surveys. METHODS: Unifactorial and
      multifactorial statistics were analyzed based on 1455 adults, with and without
      low back pain. RESULTS: One third of respondents reported no lifetime low back
      pain. Average lifetime prevalence was 59% and average annual prevalence 41%. Of
      those who reported lifetime low back pain, 42% reported persistent annual low
      back pain, 18% reported a first episode in 1997, resulting in a 4% population
      incidence rate, and 40% reported intermittent low back pain. The likelihood of
      having had low back pain increased significantly with age. Those who reported a
      new case of low back pain in 1997 were significantly more likely to be 25-34
      years of age, and these persons were most likely to report acute low back pain
      with very little disability. Those with persistent low back pain were
      significantly more likely to report chronic low back pain with some disability.
      Logistic regression modeling was unable to predict recovered versus persistent
      low back pain, given the person, pain, and treatment factors available.
      CONCLUSIONS: Results showed that low back pain is a mutable problem with acute
      episodes blending into longer periods resulting in more disability as time
      progresses. A wide range of demographic, pain, consultation, and treatment
      factors were not predictive of low back pain recovery.

PMID- 10954641
TI  - Minimal influence of facet joint anesthesia on isokinetic muscle performance in
      patients with chronic degenerative low back disorders.
AB  - STUDY DESIGN: Experimental design. OBJECTIVES: To examine the influence of pain
      reduction after facet joint injections on isokinetic back muscle performance.
      SUMMARY OF BACKGROUND DATA: Methods for evaluating the effect of facet joint
      injections vary. Recent studies base their results solely on the patient's
      subjective opinion and suggest a need for more objective, concrete, and reliable
      measurements. METHODS: Eighty-seven patients with a degenerative low back
      disorder (49 women and 38 men; mean age, 48 years; range, 22-79) who had facet
      joint injections as a part of preoperative evaluation participated. The mean
      duration of symptoms was 12.3 years (range, 1-45). The patients underwent
      isokinetic trunk flexor and extensor muscle strength testing at angular
      velocities of 60 deg/sec and 120 deg/sec. They performed two tests before the
      facet joint injections (to eliminate learning effect). All patients had bilateral
      facet joint injections at L5-S1. Those who did not report pain relief had
      additional injections at L4-L5. The flexion-extension test was repeated 15
      minutes after each injection. Pain and fear were registered on visual analog
      scales. RESULTS: All 87 patients could perform the isokinetic tests. For
      extension at 60 deg/sec, a significant improvement was found between the two
      pretests (P < 0.05). Pain increased significantly from the first to the second
      pretest (P = 0.02), and a significant decrease in pain was found after the first
      injection (P = 0.0001). Fear decreased between each test, with a significant
      decrease after the first injection. No significant change was found for the
      muscle strength measurements after facet joint anesthesia. There were only weak
      correlations between decrease in pain and alteration in muscle performance,
      ranging from 0.06 to 0.37. CONCLUSION: Pain reduction after facet joint
      injections did not influence isokinetic muscle performance in patients with
      degenerative low back disorders.

PMID- 10954642
TI  - Development and initial validation of the back pain functional scale.
AB  - STUDY DESIGN: A prospective repeated-measures design was applied. OBJECTIVES: To
      examine the measurement properties of the Back Pain Functional Scale (BPFS) and
      the Roland-Morris Questionnaire (RMQ) and to formulate hypotheses and sample size
      estimates for a subsequent comparison study. SUMMARY OF BACKGROUND DATA: Although
      there are numerous functional status measures for patients with low back pain,
      most have been conceived of and validated with a group rather than an individual
      patient as the unit of interest. Also, little has been done to formally compare
      this includes the generation of a priori hypotheses, followed by statistical
      hypotheses testing-the many competing measures. METHODS: Subjects were 77
      patients with low back pain who were referred by physicians to 10 outpatient
      physical therapy clinics located in Canada and the United States. The
      questionnaires were administered at patients' initial visits, within 48 hours of
      the initial visit, and at 1-, 2-, and 3-week follow-up visits. Reliability, cross
      sectional validity, and longitudinal validity (sensitivity to change)
      coefficients were calculated. RESULTS: Test-retest reliability estimates of 0.81
      and 0. 88 were obtained for the RMQ and BPFS, respectively. The measures
      demonstrated similar levels of cross-sectional validity. Correlations of 0.56 and
      0.65 were noted between a prognostic rating of change and the RMQ and BPFS,
      respectively. The RMQ demonstrated a ceiling effect. Approximately 180 patients
      are needed for a subsequent head-to-head comparison study of the measures.
      CONCLUSIONS: The BPFS appears to have sound measurement properties, and a formal
      head-to-head comparison study with the RMQ is warranted.

PMID- 10954643
TI  - Mechanisms of action of lumbar supports: a systematic review.
AB  - STUDY DESIGN: A systematic review and meta-analysis of studies on the putative
      mechanisms of action of lumbar supports in lifting activities. OBJECTIVE: To
      summarize the evidence bearing on the putative mechanisms of action of lumbar
      supports. SUMMARY OF BACKGROUND DATA: A restriction of trunk motion and a
      reduction in required back muscle forces in lifting are two proposed mechanisms
      of action of lumbar supports. Available studies on these putative mechanisms of
      action of lumbar supports have reported contradictory results. METHODS: A
      literature search for controlled studies on mechanisms of action of lumbar
      supports was conducted. The methodologic quality of the studies was assessed. The
      evidence for the two proposed mechanisms of action of lumbar supports was
      determined in meta-analyses. RESULTS: Thirty-three studies were selected for the
      review. There was evidence that lumbar supports reduce trunk motion for flexion
      extension and lateral bending, with overall effect sizes of 0.70 (95% confidence
      interval [CI] 0.39-1. 01) and 1.13 (95% CI 0.17-2.08), respectively. The overall
      effect size for rotation was not statistically significant (0.69; 95% CI -0. 40
      4.31). There was no evidence that lumbar supports reduce the electromyogram
      activity of erector spinae muscles (effect size of 0. 09; 95% CI -0.41-0.59) or
      increase the intra-abdominal pressure (effect size of 0.26; 95% CI -0.07-0.59).
      CONCLUSION: There is evidence that lumbar supports reduce trunk motion for
      flexion-extension and lateral bending. More research is needed on the separate
      outcome measures for trunk motion before definite conclusions can be drawn about
      the work conditions in which lumbar supports may be most effective. Studies of
      trunk motion at the workplace or during specified lifting tasks would be
      especially useful in this regard.

PMID- 10954645
TI  - Do functional tests predict low back pain?
AB  - STUDY DESIGN: A cohort of 307 nonsymptomatic workers and another cohort of 123
      workers with previous episodes of low back pain were followed up for 2 years. The
      outcomes were measured by symptoms, medical consultations, and sick leaves due to
      low back disorders. OBJECTIVES: To study the predictive value of a set of tests
      measuring the physical performance of the back in a working population. The
      hypothesis was that subjects with poor functional capacity are liable to back
      disorders. SUMMARY OF BACKGROUND DATA: Reduced functional performance has been
      associated with back pain. There are few data to show whether reduced functional
      capacity is a cause or a consequence of pain. METHODS: Mobility of the trunk in
      forward and side bending, maximal isokinetic trunk extension, flexion and lifting
      strength, and static endurance of back extension were measured. Standing balance
      and foot reaction time were recorded with a force plate. Clinical tests for the
      provocation of back or leg pain were performed. Gender, workload, age, and
      anthropometrics were managed as potential confounders in the analysis. RESULTS:
      Marked overlapping was seen in the measures of the subjects with different
      outcomes. Among the nonsymptomatic subjects, low performance in tests of mobility
      and standing balance was associated with future back disorders. Among workers
      with previous episodes of back pain, low isokinetic extension strength, poor
      standing balance, and positive clinical signs predicted future pain. CONCLUSIONS:
      Some associations were found between the functional tests and future low back
      pain. The wide variation in the results questions the value of the tests in
      health examinations (e.g., in screening or surveillance of low back disorders).

PMID- 10954644
TI  - Systematic review of psychosocial factors at work and private life as risk
      factors for back pain.
AB  - STUDY DESIGN: A systematic review of observational studies. OBJECTIVES: To assess
      whether psychosocial factors at work and in private life are risk factors for the
      occurrence of back pain. SUMMARY OF BACKGROUND DATA: Several reviews on risk
      factors for back pain have paid attention to psychosocial factors. However, in
      none of the published reviews was a strict systematic approach used to identify
      and summarize the available evidence. METHODS: A computerized bibliographical
      search of several databases was performed, restricted to studies with a cohort or
      case-control design. A rating system was used to assess the strength of the
      evidence for various factors, based on the methodologic quality of the studies
      and the consistency of the findings. RESULTS: Eleven cohort and two case-control
      studies were included in this review. Strong evidence was found for low social
      support in the workplace and low job satisfaction as risk factors for back pain.
      Insufficient evidence was found for an effect of a high work pace, high
      qualitative demands, low job content, low job control, and psychosocial factors
      in private life. CONCLUSIONS: Evidence was found for an effect of low workplace
      social support and low job satisfaction. However, the result for workplace social
      support was sensitive to slight changes in the rating system, and the effect
      found for low job satisfaction may be a result of insufficient adjustment for
      psychosocial work characteristics and physical load at work. In addition, the
      combined evaluation of job content and job control, both aspects of decision
      latitude, led to strong evidence of a role for low job decision latitude. Thus,
      based on this review, there is evidence for an effect of work-related
      psychosocial factors, but the evidence for the role of specific factors has not
      been established yet.

PMID- 10954646
TI  - Atlantoaxial subluxation associated with ossification of posterior longitudinal
      ligament of the cervical spine.
AB  - STUDY DESIGN: Two case reports. OBJECTIVE: To demonstrate two rare cases of
      atlantoaxial subluxation associated with ossification of the posterior
      longitudinal ligament of the cervical spine, in which spastic quadriplegia
      developed. SUMMARY OF BACKGROUND DATA: There are only two reports of an
      association of diffuse idiopathic skeletal hyperostosis with atlantoaxial
      subluxation. This condition often accompanies ossification of the posterior
      longitudinal ligament of the cervical spine, but there is nothing in the
      literature about the association of ossification of the posterior longitudinal
      ligament with atlantoaxial subluxation. METHODS: Clinical and radiographic
      findings of these two cases were demonstrated. In both cases laminoplasty of the
      cervical spine was performed with occipitoaxial arthrodesis. RESULTS: The spastic
      quadriplegia of these two patients caused by myelocompression improved after
      surgical intervention. CONCLUSION: Ossification of the posterior longitudinal
      ligament of the cervical spine may cause atlantoaxial subluxation.

PMID- 10954647
TI  - Spontaneous atlantoaxial rotatory fixation in old age after cerebral infarction:
      case report.
AB  - STUDY DESIGN: Case report of spontaneous Fielding and Hawkins Type I atlantoaxial
      rotatory fixation in a 78-year-old man after hemiplegia and homonymous
      hemianopsia caused by cerebral infarction. OBJECTIVES: To describe a case of
      spontaneous atlantoaxial rotatory fixation in old age and review previous adult
      cases of atlantoaxial rotatory fixation without fracture. SUMMARY OF BACKGROUND
      DATA: Atlantoaxial rotatory fixation in adults is a relatively rare finding and
      is mainly caused by trauma. To the author's knowledge, there has been no previous
      report of spontaneous atlantoaxial rotatory fixation in old age. METHODS: The
      patient's head was fixed in a 40 degrees left-rotated position. Left hemiplegia
      and homonymous left-side hemianopsia developed due to cerebral infarction.
      Computed tomography of the cervical spine clearly showed rotatory fixation of the
      atlas on the axis. RESULTS: Successful reduction was obtained after 1 day of
      skull traction. CONCLUSIONS: It was hypothesized that repeated left-rotational
      stress due to homonymous hemianopsia loaded to the atlantoaxial joint caused
      abnormal laxity of the joint.

PMID- 10954649
TI  - Imaging corner

PMID- 10954648
TI  - Alkaptonuria with lumbar disc herniation: a report of two cases.
AB  - STUDY DESIGN: Two cases of lumbar disc herniation with alkaptonuria are
      presented. OBJECTIVES: To present a probable clinical course of lumbar disc
      herniation with alkaptonuria, a rare metabolic disease. SUMMARY OF BACKGROUND
      DATA: Although lumbar disc disease is a common clinical occurrence in
      alkaptonuria, lumbar disc surgery is needed rarely in this disease. A patient
      with alkaptonuria without ochronotic signs is also rarely seen. METHODS: The
      cause, clinical presentation, diagnostic techniques and treatment of alkaptonuria
      with lumbar disc disease are reviewed. RESULTS: The symptoms of the patients
      disappeared after surgery, and there were no symptoms on follow-up. CONCLUSION:
      Alkaptonuria frequently occurs in association with lumbar disc disease. In
      patients with no other signs of alkaptonuria or ochronosis, early detection of
      the disease is important to treat involvement of other systems (e.g.,
      cardiovascular and urinary).

PMID- 10954650
TI  - Re: Results of a multimodal program for patients with chronic symptoms after a
      whiplash injury of the neck.

PMID- 10954651
TI  - Imagery

PMID- 10954652
TI  - MR imaging of vanishing white matter.

PMID- 10954653
TI  - An overview of sexually transmitted diseases. Part III. Sexually transmitted
      diseases in HIV-infected patients.
AB  - The HIV epidemic has dramatically altered the field of sexually transmitted
      diseases (STDs). HIV infection is unique among sexually transmitted diseases
      because it can modify the clinical presentation and features of other STDs.
      Conversely, other STDs can affect the transmission of HIV. This review is the
      third part of a series that has provided a general overview of STDs. In this
      article, genital ulcer diseases (genital herpes, syphilis, chancroid,
      lymphogranuloma venereum, and granuloma inguinale), human papillomavirus
      infection (anogenital warts and subclinical infections), molluscum contagiosum,
      human herpesvirus 8 infection, viral hepatitis, and ectoparasitic infestations
      (scabies and pediculosis pubis) are discussed as they occur in HIV-infected
      hosts. Additional features as they relate to HIV-infected patients, such as
      epidemiology and transmission, are discussed when applicable. LEARNING OBJECTIVE:
      At the conclusion of this learning activity, participants should improve their
      understanding of sexually transmitted diseases in the HIV-infected host.

PMID- 10954654
TI  - Dermatologic changes associated with roquinimex immunotherapy after autologous
      bone marrow transplant.
AB  - BACKGROUND: Roquinimex (Linomide) is an immunotherapeutic agent used in
      conjunction with autologous bone marrow transplantation (ABMT) for treatment of
      acute and chronic myelogenous leukemia (AML and CML). This agent may induce graft
      versus-host reactions (GVHR) as well as graft-versus-leukemia (GVL) effects.
      OBJECTIVE: We documented the incidence of acute cutaneous GVHR associated with
      roquinimex immunotherapy. The presence or absence of autologous GVHR was also
      correlated with a potential GVL effect in patients with CML treated with ABMT and
      subsequent roquinimex immunotherapy in the period after the transplant. METHODS:
      Fifteen patients undergoing bone marrow transplantation and roquinimex
      immunotherapy for CML were followed up, and clinicopathologic data were analyzed.
      RESULTS: Acute cutaneous GVHRs were observed in 6 of 15 patients (40%) treated
      with roquinimex. Ten of 11 evaluable patients receiving roquinimex exhibited
      eccrine sweat gland necrosis (ESGN) (90.9%), which was independent of the acute
      GVHR. Neither bone marrow engraftment status nor the survival rates of patients
      with and without GVHR was significantly different. CONCLUSION: Roquinimex
      immunotherapy enhances the incidence of GVHR and was associated with a high rate
      of ESGN in patients with CML who were undergoing ABMT. There was no significant
      association between ESGN and acute GVHR. Acute autologous GVHR caused by
      roquinimex did not correlate with a GVL effect in our study of 15 patients with
      CML.

PMID- 10954655
TI  - Hair removal with an 800-nm pulsed diode laser.
AB  - BACKGROUND AND OBJECTIVE: Laser hair removal is a relatively new procedure. Our
      purpose was to study the efficacy and safety of a high-power, pulsed diode laser
      array for removing unwanted hair. METHODS: A total of 38 subjects were treated
      with a prototype of the 800-nm diode laser system. Fluences ranging from 10 to 40
      J/cm(2) (mean, 33.4 J/cm(2)) were used and 1 to 4 treatments (mean, 2.7) were
      performed. Evaluation of hair loss was performed at least 4 months after the last
      treatment (mean, 8.7 months) by a blinded assessment of clinical photographs.
      RESULTS: A total of 59% of the subjects had only sparse hair regrowth at the
      final follow-up. Higher fluences and multiple treatments produced greater long
      term efficacy. Transient pigmentary changes occurred in 29% of the subjects and
      were more common in darker skin types IV to VI (P =. 047). CONCLUSION: The 800-nm
      diode laser is an efficient and safe technique for hair reduction. Adverse
      pigmentary effects occur, but are transient.

PMID- 10954656
TI  - Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor) on T
      cells by administration of humanized anti-Tac antibody to patients with
      psoriasis.
AB  - BACKGROUND: Daclizumab is a humanized antibody to the alpha-subunit (CD25) of the
      interleukin 2 (IL-2) receptor that blocks normal IL-2 binding to this receptor.
      Because IL-2 is a major stimulus for T-cell growth, blockade of the IL-2 receptor
      could be useful in treating T-cell-mediated (autoimmune) diseases. OBJECTIVE: Our
      purpose was to determine whether adequate concentrations of antibody were
      achieved in circulating blood and in psoriatic skin lesions to saturate CD25
      receptors. We also intended to measure clinical effect and safety of this agent
      when used alone (without other immunosuppressive drugs) in psoriasis. METHODS:
      Nineteen patients with psoriasis in two centers received daclizumab at an initial
      dose of 2 mg/kg, then 1 mg/kg at weeks 2, 4, 8, and 12. To determine whether CD25
      was blocked in vivo, flow cytometric studies measured (1) expression of CD25 on
      CD3(+) T cells derived from blood and (2) immuno-histochemistry measures of
      CD25(+) cells done on pretreatment and posttreatment biopsy specimens. Patients
      were followed up clinically with photographs and Psoriasis Area and Severity
      Index scores. RESULTS: This study showed a consistent blockade of CD25 in
      peripheral blood and tissue during the first 4 weeks of therapy while the dosing
      was every 2 weeks. Variable desaturation of receptors began after 4 weeks, which
      correlated with a reversal in disease improvement. Patients with a pretreatment
      Psoriasis Area and Severity Index score of less than 36 showed a mean reduction
      in severity by 30% at 8 weeks (P =.02). During the 16 weeks of treatment, a 44.8%
      decrease in expression of the IL-2 receptor alpha-subunit was found. The absolute
      T-cell counts were calculated and showed no significant changes during the course
      of the study. No significant adverse events were produced by daclizumab during
      this study. CONCLUSION: We therefore conclude that daclizumab is a well-tolerated
      agent that blocks CD25 expression in peripheral blood and skin. Furthermore, it
      may be useful in treating psoriasis in some patients.

PMID- 10954657
TI  - Preoperative assessment of melanoma thickness by ABCD score of dermatoscopy.
AB  - BACKGROUND: Epiluminescence microscopy is a useful tool for the noninvasive
      diagnosis of malignant melanoma based on criteria that have been correlated with
      specific histologic characteristics. Previous studies have also shown a good
      correlation between the frequency of some dermatoscopic criteria based on pattern
      analysis (pigment network, blue-gray areas, vascular pattern) and tumor
      thickness. This technique could be useful in the preoperative assessment of tumor
      thickness as an indication for sentinel node biopsy. OBJECTIVE: Our purpose was
      to evaluate the possible role of the total dermatoscopy score (TDS) assigned to a
      series of lesions in accordance with the ABCD rule of dermatoscopy as a
      preoperative predictor of melanoma thickness. METHODS: For 84 cutaneous melanomas
      (17 were in situ melanomas; 67 invasive cases with mean thickness 0. 93 mm;
      range, 0.2-3.9 mm; standard deviation, 0.63) consecutively excised at the
      Department of Dermatology of Florence, TDS was established by two observers
      blinded as to the tumor thickness. The performance of different cut-off points of
      TDS in the diagnosis of melanoma with Breslow's thickness more than 0.75 or 1.00
      mm was investigated by receiver operating characteristic (ROC) analysis. Accuracy
      of classification was evaluated in terms of sensitivity, specificity, and area
      under ROC curves (AUC). RESULTS: The TDS assigned to cutaneous melanomas by the
      ABCD rule increased with the thickness of the lesions from in situ melanomas to
      melanomas of intermediate thickness (0.75-1.50 mm). As a preoperative method for
      the detection of melanomas with a Breslow thickness greater than 0. 75 mm, a TDS
      cut-off point of 6.80 showed 80% sensitivity, 84% specificity, and 82% diagnostic
      accuracy (AUC value, 0.90). TDS performed better in the diagnosis of a thickness
      threshold of 0.75 than 1.00 mm (higher AUC value). CONCLUSION: The TDS calculated
      by the ABCD rule of dermatoscopy-a simplified approach to dermatoscopic diagnosis
      of melanoma-provides useful information for the preoperative assessment of
      melanoma thickness greater than 0.75 mm.

PMID- 10954658
TI  - Follow-up of melanocytic skin lesions with digital epiluminescence microscopy:
      patterns of modifications observed in early melanoma, atypical nevi, and common
      nevi.
AB  - BACKGROUND: Digital epiluminescence microscopy (DELM) has been reported to be a
      useful technique for the follow-up of melanocytic nevi. One of the promises of
      this technique is to identify modifications over time that indicate impending or
      incipient malignancy and to facilitate surveillance of melanocytic skin lesions,
      particularly in patients with multiple clinically atypical nevi. OBJECTIVE: Our
      purpose was to report on patterns of modifications over time observed in benign
      melanocytic skin lesions and melanoma. METHODS: A total of 1862 sequentially
      recorded DELM images of melanocytic lesions from 202 patients (mean age, 36.1
      years; 54.0% female patients) with multiple clinically atypical nevi were
      included in the analysis. The median follow-up interval was 12. 6 months.
      Melanocytic lesions with substantial modifications over time (enlargement,
      changes in shape, regression, color changes or appearance of ELM structures known
      to be associated with melanoma) were excised and referred to histopathologic
      examination. RESULTS: A total of 75 melanocytic skin lesions (4.0%) from 52
      patients (mean age, 33.3 years; 63.5% female patients) showed substantial
      modifications over time and were excised and referred to histopathologic
      examination. Eight changing lesions were histologically diagnosed as early
      melanomas. These lesions frequently showed focal enlargement associated with a
      change in shape as well as appearance of ELM structures that are known to be
      associated with melanoma. In contrast, the majority of benign changing lesions
      (common and atypical nevi) showed symmetric enlargement without substantial
      structural ELM changes. Six of the 8 patients in whom melanoma developed were
      unaware of the fact that the lesion had changed over time. CONCLUSION: We
      demonstrate that follow-up of melanocytic lesions with DELM helps to identify
      patterns of morphologic modifications typical for early melanoma. DELM may
      therefore serve as a useful tool to improve the surveillance of patients with
      multiple atypical nevi.

PMID- 10954659
TI  - Fractionated radiotherapy of lentigo maligna and lentigo maligna melanoma in 64
      patients.
AB  - Between 1987 and 1998, 64 patients with lentigo maligna (LM) (n = 42) or lentigo
      maligna melanoma (LMM) (n = 22) were treated by fractionated radiotherapy. In all
      22 patients with LMM, excision of the nodular part of the LMM was performed
      before radiation of the residual lentiginous tumor. During the follow-up period
      of 1 to 96 months (mean, 23 months; median, 15 months), none of the 42 patients
      with LM displayed any signs of recurrence of LM after radiation therapy alone. Of
      the 22 patients with LMM, only 2 patients showed local recurrence of the tumor,
      salvaged by excision in both cases. One patient with LMM suffered from metastatic
      disease without local recurrence of the melanoma 44 months after radiation
      therapy. The cosmetic results of radiotherapy were good or excellent in the vast
      majority of patients, with only a few experiencing hypopigmentation or
      hyperpigmentation in the irradiated area. Fractionated radiation therapy with
      superficial x-rays is an effective method of treatment of LM associated with low
      morbidity and leading to clinical results comparable to those of surgical
      excision.

PMID- 10954660
TI  - Combined sentinel lymphadenectomy and mohs micrographic surgery for high-risk
      cutaneous squamous cell carcinoma.
AB  - BACKGROUND: There are subgroups of cutaneous squamous cell carcinoma (SCC) that
      have a higher risk for both regional and distant metastasis. When cutaneous SCC
      does metastasize, it typically spreads first to local nodal groups. Sentinel
      lymph node (SLN) localization has been successfully used to evaluate nodal
      metastasis in breast carcinoma, melanoma, and other select tumors. It may also be
      useful in certain high-risk cutaneous SCCs. Currently, Mohs micrographic surgery
      is the treatment of choice for these tumors. METHODS: A patient presented with a
      high-risk recurrent SCC on the forehead. The regional nodal groups were
      clinically negative and radiographically negative by computed tomographic scan.
      Sentinel lymphadenectomy was performed by means of technetium 99m-radiolabeled
      sulfur colloid. The main tumor was resected with Mohs micrographic surgery.
      RESULTS: A left preauricular SLN was localized by lymphoscintigraphy. The SLN was
      located intraoperatively by means of a gamma probe and excised. Subsequent
      pathologic evaluation of the SLN was negative for evidence of metastatic SCC by
      light microscopy with hematoxylin and eosin, and with immunohistochemical stains
      for cytokeratins AE1 and AE3. The day after SLN excision, the tumor was removed
      via Mohs micrographic surgery with clear surgical margins after a total of 8
      stages. Aggressive subclinical spread by both subcutaneous "skating" and
      perineural invasion was noted. CONCLUSION: The combination of Mohs micrographic
      surgery and sentinel lymphadenectomy is feasible and has theoretical utility in
      the management of a subset of cutaneous SCCs at high risk for metastasis. The
      ability of sentinel lymphadenectomy to identify regionally metastatic cutaneous
      SCC as well as the additive benefit of SLN and Mohs micrographic extirpation in
      the treatment of high-risk cutaneous SCC remain to be further clarified.

PMID- 10954661
TI  - Vascular changes in erythropoietic protoporphyria: histopathologic and
      immunohistochemical study.
AB  - BACKGROUND: Erythropoietic protoporphyria (EPP) is an inherited disease caused by
      deficient activity of ferrochelatase in the heme biosynthetic pathway.
      Accumulation of protoporphyrins and light exposure results in acute phototoxic
      skin reactions. The histopathologic findings of the light-exposed skin are
      thickening of the superficial dermal vessel walls and amorphous deposits around
      the vessels, but the origin and detailed composition of the perivascular material
      have been unclear. OBJECTIVE: The vascular morphology and composition of the
      perivascular material were studied in the skin samples of patients with EPP.
      METHODS: Skin biopsy specimens of 8 patients with EPP representing 7 Finnish EPP
      families with different genotypes were studied by means of light and electron
      microscopy and immunohistochemical methods. RESULTS: The characteristic finding
      was thickened, periodic acid-Schiff-positive vessel walls caused by concentric
      reduplication of basal lamina and excess of fine granular material at the basal
      membrane zone in the superficial dermis. The perivascular deposits in the
      vicinity of vessel walls had a homogeneous or fine granular appearance without
      filaments. Direct immunofluorescence showed constant IgG deposits together with
      IgA, IgM, and C3 in the vessel walls. In immunohistochemistry, collagen IV and
      laminin could be demonstrated at the vascular basal membrane together with serum
      amyloid P protein, kappa and lambda light chains, and a 90-kd glycoprotein.
      CONCLUSION: The vascular involvement indicates that the blood vessel walls in the
      papillary dermis are the primary tissues affected during an acute photoreaction.
      The repeated acute damage and repair processes in the basement membrane zone
      result in thickening of the vessel walls. Perivascular deposits are a secondary
      and irreversible phenomenon resulting from the leakage and accumulation of
      different serum components. These changes were not found in the nonexposed skin,
      indicating that an increased level of erythrocyte protoporphyrin per se is not
      responsible for the cutaneous manifestations, but the interaction of solar
      radiation is mandatory. Amorphous deposits distinguish EPP from variegate
      porphyria and porphyria cutanea tarda; a histopathologic examination may be a
      helpful tool in differentiating porphyric and nonporphyric photosensitivity.

PMID- 10954662
TI  - Low-dose adjunctive spironolactone in the treatment of acne in women: a
      retrospective analysis of 85 consecutively treated patients.
AB  - BACKGROUND: Despite advances in acne therapy in recent years, treatment failures
      are common, especially in adult women. Spironolactone, an established androgen
      receptor blocker, is successful in treating adult women with acne, but side
      effects are common at the doses reported in published studies to date. OBJECTIVE:
      The purpose of this study was to assess the therapeutic effect and tolerance of
      low doses of spironolactone used alone or as an adjunct in the treatment of acne
      in adult women. METHODS: Records were reviewed from 85 women with acne treated
      consecutively with spironolactone 50 to 100 mg/day, administered either as single
      drug therapy or as an adjunct to standard therapies. The maximum length of
      treatment was 24 months. RESULTS: Clearing of acne occurred in 33% of patients
      treated with low doses of spironolactone; 33% had marked improvement, 27.4%
      showed partial improvement, and 7% showed no improvement. The treatment regimen
      was well tolerated, with 57.5% reporting no adverse effects. CONCLUSION:
      Spironolactone can be used in low doses as a single drug or as an adjunct to
      standard acne therapies in women with adult acne. When used in this fashion,
      treatment outcomes are favorable, and the drug is well tolerated.

PMID- 10954663
TI  - Childhood molluscum contagiosum: experience with cantharidin therapy in 300
      patients.
AB  - BACKGROUND: Molluscum contagiosum (MC) is a common cutaneous infection in
      children. Cantharidin, a chemovesicant that is highly effective in treating MC,
      has lost favor with some physicians because of concerns over its safety.
      OBJECTIVE: We attempted to determine the safety, efficacy, and parental
      satisfaction of cantharidin therapy for MC in children who were treated in a
      pediatric dermatology clinic at a large referral hospital. METHODS: A total of
      537 charts of children who presented with MC were reviewed. We found 300 children
      who were treated with cantharidin and who had parents available for telephone
      interview, which was performed in addition to chart review. RESULTS: With
      cantharidin therapy, 90% of patients experienced clearing and 8% improved. The
      average number of treatment visits was 2.1. Blisters occurred at sites of
      application in 92% of patients. Temporary burning, pain, erythema, or pruritus
      was reported in 6% to 37% of patients. No major side effects were reported, and
      no patients experienced secondary bacterial infection. A total of 95% of parents
      reported they would proceed with cantharidin therapy again. CONCLUSION: To our
      knowledge ours is the largest retrospective series of childhood MC treated with
      cantharidin. In these patients the therapy was extremely effective and well
      tolerated, and parental satisfaction was high. Cantharidin is a safe and
      effective therapy for MC in children.

PMID- 10954664
TI  - Primary closure for midline defects of the nose: a simple approach for
      reconstruction.
AB  - We present a modification of the standard linear closure for small to medium
      sized defects of the lower nose that avoids many of the limitations of flap or
      graft reconstruction. The surgical technique detailed yields predictable
      functional and cosmetic reconstruction with very few complications. The
      dermatologic surgeon should consider this option when reconstructing defects of
      the lower nose.

PMID- 10954665
TI  - Lichenoid keratosis: a clinicopathologic study of 17 patients.
AB  - BACKGROUND: Lichenoid keratosis (LK) is a rather frequent skin lesion that has
      some histologic features similar to lichen planus (LP). The clinical and
      histopathologic characteristics of LK and differential tools from LP are not yet
      fully established. OBJECTIVE: The purpose of this study was to investigate the
      clinical and histopathologic characteristics of LK. METHODS: A clinical survey
      was done with 17 patients diagnosed as having LK. We reevaluated biopsy materials
      of 17 patients diagnosed during the past 10 years at Asan Medical Center, Seoul,
      Korea. We performed an immunohistochemical staining in 17 cases of LK and 7 cases
      of LP using 5 antibodies for CD3, CD4, CD8, CD20, and cutaneous lymphocyte
      associated antigen (CLA). Standard streptavidin-biotin peroxidase method using
      the monoclonal antibodies with 3-amino-9-ethyl-carbazole was used. RESULTS: The
      male/female ratio was 1:1.1. The mean age at diagnosis was 54.9 years. The face
      was the most commonly affected site, followed by the arm and forearm, dorsum of
      hand, chest, trunk, abdomen, and leg. The lesions were predominantly solitary
      (76.5%); 1 patient had 4 lesions; 3 patients (17.6%) had numerous lesions. The
      lesions ranged in size from 0.4 to 2.0 cm. Histopathologically, all the cases
      showed characteristic lichenoid infiltrates of lymphocytes, occasional
      parakeratosis, and apoptotic bodies in the epidermis without nuclear atypia of
      keratinocytes. LK could be reclassified into 3 patterns by means of
      histopathologic findings: LP-like (11/17), seborrheic keratosis-like (3/17), and
      lupus erythematosus-like (3/17). Immunohistochemical studies revealed that
      infiltrated epidermal and dermal lymphocytes in LK consisted mainly of CD8(+) T
      cells and partly CD20(+) B cells. In LP, epidermal lymphocytes were mainly CD8(+)
      T cells and dermal lymphocytes were CD4(+) or CD8(+) T cells. Interestingly, CLA
      was strongly expressed in LP but not expressed in LK. CONCLUSION: We reclassified
      LK as follows: LP-like LK, seborrheic keratosis-like LK, and lupus erythematosus
      like LK. Immunohistochemical stains for CLA as well as CD4 and CD8 may be
      valuable tools in the differential diagnosis between LK and LP.

PMID- 10954666
TI  - Incontinentia pigmenti.

PMID- 10954667
TI  - Nineteenth-century patent medicines for the skin and hair.

PMID- 10954668
TI  - Surgical pearl: the use of the no. 12 scalpel blade for the removal of sutures.

PMID- 10954669
TI  - Nail involvement in pemphigus vulgaris.
AB  - Nail involvement in pemphigus vulgaris is relatively rare. We describe a case of
      severe pemphigus involving both the skin and oral mucosa in which an acute
      exacerbation was preceded by the onset of nail involvement of all 4 extremities.
      Nail involvement occurred in the form of hemorrhagic paronychia of multiple
      digits. Oral, cutaneous, and nail manifestations of the disease were all well
      controlled by systemic therapy. A review of the literature on nail involvement in
      pemphigus reveals that this involvement may be manifested in multiple ways, with
      chronic paronychia and onychomadesis being the most common. Involvement of the
      nail occurs most frequently either as part of the initial presentation, or just
      before or concurrent with a flare of pre-existing disease. Nail involvement, when
      it occurs, is usually present when the disease is severe. Topical therapy is
      insufficient, and systemic therapy is warranted. In the majority of cases, nail
      recovery is complete, with no residual damage.

PMID- 10954670
TI  - Primary tuberculous chancre caused by Mycobacterium bovis after goring with a
      bull's horn.
AB  - A 14-year-old boy was gored by a bull during festival celebrations. The horn of
      the bull caused a wound on his left hand and after 3 months it was a accompanied
      by an ulcerated nodule on the left upper arm and an axillary adenopathy. The
      tuberculin test was positive and a culture of the aspiration biopsy specimen of
      the axillary lymph node yielded Mycombacterium bovis.

PMID- 10954671
TI  - A case of subcutaneous cysticercosis (Cysticercus cellulosae cutis).
AB  - Cysticercosis is an infection resulting from the larval form of the pork
      tapeworm, and domestic infection is rare in Japan. We report a case of
      Cysticercus cellulosae cutis in a Japanese woman who was thought to be infected
      in an endemic area and offer a brief review of the literature.

PMID- 10954672
TI  - Persistent serpentine supravenous hyperpigmented eruption as an adverse reaction
      to chemotherapy combining actinomycin and vincristine.
AB  - A 15-year-old boy experienced a macular serpentine erythematous eruption that
      subsided with a persistent hyperpigmentation overlying the superficial venous
      network of the left forearm. This reaction occurred at the injection site of a
      chemotherapy regimen that combined actinomycin and vincristine a few hours after
      the first course. After a single injection of actinomycin in the right arm, a
      similar reaction occurred, implicating it as the responsible agent. A skin biopsy
      specimen demonstrated a cell-poor interface tissue reaction associated with an
      eccrine neutrophilic hidradenitis. To our knowledge, this is the first case of
      persistent supravenous serpentine hyperpigmented eruption reported in a child
      treated with this particular drug combination.

PMID- 10954673
TI  - IgA pemphigus: a case report and its characteristic clinical features compared
      with subcorneal pustular dermatosis.
AB  - We report a case of IgA pemphigus. A 35-year-old woman had vesiculopustular
      eruptions on her scalp, trunk, and extremities. Histologic examination showed a
      subcorneal pustule containing numerous neutrophils without acantholysis. Direct
      immunofluorescence revealed IgA deposits in the intercellular space throughout
      the epidermis, more intense in superficial layers and less intense in lower
      layers. The titer of circulating IgA antibodies was 1:160 in normal human skin as
      a substrate. Skin lesions responded to dapsone. The IgA autoantibody from this
      patient did not react with desmogleins or desmocollins when immunoblotting,
      enzyme-linked immunosorbent assay, or complement DNA transfection was used. We
      consider the characteristic clinical features that favor the diagnosis of IgA
      pemphigus rather than classic subcorneal pustular dermatosis as follows: (1) the
      lesions involve the scalp and/or face, and (2) the distribution of the lesions is
      more widespread.

PMID- 10954674
TI  - The dermatology-industry interface: defining the boundaries.
AB  - Support from industry has become an important factor in the growth of the
      dermatologic profession. However, the relationship creates inevitable conflicts
      of interest. This article explores these potential conflicts, including (1)
      giving and receiving of gifts, (2) conduct of clinical trials, (3) appearance of
      advertisements in professional journals, (4) continuing medical education
      programs and educational grants to societies and departments, and (5) drug
      sampling.

PMID- 10954675
TI  - Topical imiquimod treatment of a cutaneous melanoma metastasis.

PMID- 10954676
TI  - Wells syndrome associated with Churg-Strauss syndrome.

PMID- 10954677
TI  - Treatment of lipodermatosclerosis with oxandrolone in a patient with stanozolol
      induced hepatotoxicity.

PMID- 10954678
TI  - Androgen receptors and lichen sclerosus.

PMID- 10954680
TI  - Effect of polaprezinc on healing of acetic acid-induced stomatitis in hamsters.
AB  - PURPOSE: The purpose of this work was to investigate the potential effectiveness
      of polaprezinc in the treatment of stomatitis. Its effect on oral mucous membrane
      lesions was studied focusing on acetic acid-induced stomatitis in an animal
      model. METHOD: Stomatitis was induced in hamsters by local injection of 30 microL
      of 10% acetic acid solution into both cheek pouches. Change of the size of the
      acetic acid-induced white lesion caused by polaprezinc injection was compared
      with that of control (water injection). The process of healing of damaged
      membrane was also investigated histopathologically. Selective adhesion of
      polaprezinc on mucous membrane was studied using color development by
      complexation between zinc and dithizone. RESULTS: On day 4 after acetic acid
      injection, round white lesions were observed in the central area of both pouches.
      Observation on days 7, 10, and 14 showed that the size of the lesions decreased
      with time. Comparison with the control group of animals, in which healing took
      place naturally, showed that daily administration of polaprezinc (10 mg/kg)
      applied to the cheek pouches significantly promoted healing of the lesion from
      day 7 onward. Histopathological investigation of the mucous membrane in the cheek
      pouches 7 days after the induction of stomatitis by acetic acid injection showed
      thickening, and cell damage was evident. In the group of animals treated with
      polaprezinc, the thickening of the mucous membrane was less than that in animals
      of the group receiving no treatment and regeneration of damaged tissue was
      observed after 6 days of polaprezinc treatment. CONCLUSION: Polaprezinc is an
      effective treatment in this animal model of acetic acid-induced stomatitis. This
      suggests that the drug may be useful in promoting healing of stomatitis in the
      clinical setting. Extrapolating these to humans suggests that the drug has
      healing effect to severe stomatitis induced by anticancer drug therapy.

PMID- 10954681
TI  - A new method for one-step, no-carrier-added synthesis of cholesteryl 4-[18F]
      fluorobenzoate ([18F]-CFB), a radiotracer used in detection of adrenal
      malignancies.
AB  - PURPOSE: Cholesteryl 4-[(18)F]-fluorobenzoate, a potential radiotracer used for
      adrenal and ovarian imaging, was prepared in no-carrier-added form from
      cholesteryl 4-N,N,N-trimethylanilinium trifluoromethanesulfonate. METHODS: The
      reaction was performed in one step using Kryptofix2.2.2/[(18)F], carbonate as the
      counter ion and dimethyl sulfoxide as the solvent at 110 degrees C. Purification
      was performed using commercially available C(18) and Si Sep-Paks. RESULTS: Column
      purification afforded the desired compound in 75-85 % radiochemical yield (EOS)
      with a specific activity about 74 KBq/mmole in about 20 minutes, with greater
      than 95% radiochemical and chemical purity (HPLC and TLC analysis). CONCLUSIONS:
      This compound was prepared through a novel method which can be easily performed
      at distant locations from the main radionuclide production centers using Sep
      Paks. The biodistribution of this compound in mice was confirmed to be similar to
      that reported in the literature.

PMID- 10954682
TI  - Modulation of the pharmacokinetics and pharmacodynamics of proteins by
      polyethylene glycol conjugation.

PMID- 10954683
TI  - Detection and prevention of NSAID-induced enteropathy.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) may cause damage distal to the
      duodenum. We reviewed the prevalence, clinical spectrum, assessment,
      pathogenesis, and treatment of adverse effects of NSAIDs on the small intestine.
      NSAIDs can cause small intestinal perforation, ulcers, and strictures requiring
      surgery. NSAIDs produce inflammation of the small intestine in 40 to 70% in long
      term users, and the associated complications of blood loss and protein loss are
      difficult management problems. The pathogenesis of NSAID enteropathy is a multi
      stage process involving specific biochemical and subcellular organelle damage
      followed by inflammatory tissue reaction. Various suggested treatments of NSAID
      induced enteropathy (e.g., sulphasalazine, misoprostol, and metronidazole) have
      yet to undergo rigorous clinical trials. Cyclo-oxygenase-2 inhibitors appear to
      be safer to the small intestine than traditional NSAIDs. Pre-clinical and
      clinical data suggests meloxicam, celecoxib, nimesulide and rofecoxib may have
      less small intestine toxicity than traditional non-selective NSAIDs.

PMID- 10954684
TI  - Accuracy of haplotype frequency estimation for biallelic loci, via the
      expectation-maximization algorithm for unphased diploid genotype data.
AB  - Haplotype analyses have become increasingly common in genetic studies of human
      disease because of their ability to identify unique chromosomal segments likely
      to harbor disease-predisposing genes. The study of haplotypes is also used to
      investigate many population processes, such as migration and immigration rates,
      linkage-disequilibrium strength, and the relatedness of populations.
      Unfortunately, many haplotype-analysis methods require phase information that can
      be difficult to obtain from samples of nonhaploid species. There are, however,
      strategies for estimating haplotype frequencies from unphased diploid genotype
      data collected on a sample of individuals that make use of the expectation
      maximization (EM) algorithm to overcome the missing phase information. The
      accuracy of such strategies, compared with other phase-determination methods,
      must be assessed before their use can be advocated. In this study, we consider
      and explore sources of error between EM-derived haplotype frequency estimates and
      their population parameters, noting that much of this error is due to sampling
      error, which is inherent in all studies, even when phase can be determined. In
      light of this, we focus on the additional error between haplotype frequencies
      within a sample data set and EM-derived haplotype frequency estimates incurred by
      the estimation procedure. We assess the accuracy of haplotype frequency
      estimation as a function of a number of factors, including sample size, number of
      loci studied, allele frequencies, and locus-specific allelic departures from
      Hardy-Weinberg and linkage equilibrium. We point out the relative impacts of
      sampling error and estimation error, calling attention to the pronounced accuracy
      of EM estimates once sampling error has been accounted for. We also suggest that
      many factors that may influence accuracy can be assessed empirically within a
      data set-a fact that can be used to create "diagnostics" that a user can turn to
      for assessing potential inaccuracies in estimation.

PMID- 10954686
TI  - The impairment in endothelial function induced by non-esterified fatty acids can
      be reversed by insulin.
AB  - Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides)
      and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in
      the same subjects, the so-called 'insulin resistance syndrome'. The present study
      aims to investigate how elevated levels of non-esterified fatty acids,
      hyperinsulinaemia and the combination of these factors affects endothelium
      dependent vasodilatation (EDV). Ten volunteers were examined on two occasions.
      Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the
      final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and
      endothelium-independent vasodilatation were evaluated in the forearm by local
      intra-arterial infusion of methacholine or sodium nitroprusside at baseline and
      after 2 and 4 h. Forearm blood flow was measured by venous occlusion
      plethysmography. Lipid oxidation was determined by measuring plasma
      malondialdehyde levels. Infusion of Intralipid plus heparin increased the
      concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV
      from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This
      effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia
      alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01),
      while endothelium-independent vasodilatation was unaltered by the interventions.
      Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/
      0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change
      the malondialdehyde level. In conclusion, an acute increase in serum levels of
      non-esterified fatty acids increased lipid oxidation and decreased EDV. The
      effect on EDV of non-esterified fatty acids could be reversed by
      hyperinsulinaemia.

PMID- 10954699
TI  - Solution structure of the E200K variant of human prion protein. Implications for
      the mechanism of pathogenesis in familial prion diseases.
AB  - Prion propagation in transmissible spongiform encephalopathies involves the
      conversion of cellular prion protein, PrP(C), into a pathogenic conformer,
      PrP(Sc). Hereditary forms of the disease are linked to specific mutations in the
      gene coding for the prion protein. To gain insight into the molecular basis of
      these disorders, the solution structure of the familial Creutzfeldt-Jakob disease
      related E200K variant of human prion protein was determined by multi-dimensional
      nuclear magnetic resonance spectroscopy. Remarkably, apart from minor differences
      in flexible regions, the backbone tertiary structure of the E200K variant is
      nearly identical to that reported for the wild-type human prion protein. The only
      major consequence of the mutation is the perturbation of surface electrostatic
      potential. The present structural data strongly suggest that protein surface
      defects leading to abnormalities in the interaction of prion protein with
      auxiliary proteins/chaperones or cellular membranes should be considered key
      determinants of a spontaneous PrP(C) --> PrP(Sc) conversion in the E200K form of
      hereditary prion disease.

PMID- 10954700
TI  - Kinetic role for mammalian SF1/BBP in spliceosome assembly and function after
      polypyrimidine tract recognition by U2AF.
AB  - Two sequences important for pre-mRNA splicing precede the 3' end of introns in
      higher eukaryotes, the branch point (BP) and the polypyrimidine (Py) tract.
      Initial recognition of these signals involves cooperative binding of the splicing
      factor SF1/mammalian branch point binding protein (mBBP) to the BP and of
      U2AF(65) to the Py tract. Both factors are required for recruitment of the U2
      small nuclear ribonucleoprotein particle (U2 snRNP) to the BP in reactions
      reconstituted from purified components. In contrast, extensive depletion of
      ST1/BBP in Saccharomyces cerevisiae does not compromise spliceosome assembly or
      splicing significantly. As BP sequences are less conserved in mammals, these
      discrepancies could reflect more stringent requirements for SF1/BBP in this
      system. We report here that extensive depletion of SF1/mBBP from nuclear extracts
      of HeLa cells results in only modest reduction of their activity in spliceosome
      assembly and splicing. Some of these effects reflect differences in the kinetics
      of U2 snRNP binding. Although U2AF(65) binding was reduced in the depleted
      extracts, the defects caused by SF1/mBBP depletion could not be fully restored by
      an increase in occupancy of the Py tract by exogenously added U2AF(65), arguing
      for a role of SF1/mBBP in U2 snRNP recruitment distinct from promoting U2AF(65)
      binding.

PMID- 10954701
TI  - Involvement of T-complex protein-1delta in dopamine triggered apoptosis in chick
      embryo sympathetic neurons.
AB  - The neurotransmitter dopamine (DA) is capable of inducing apoptosis in post
      mitotic sympathetic neurons via its oxidative metabolites. The differential
      display method was applied to cultured sympathetic neurons in an effort to detect
      genes whose expression is transcriptionally regulated during the early stages of
      DA-triggered apoptosis. One of the up-regulated genes was identified as the chick
      homologue to T-complex polypeptide-1delta (TCP-1delta), a member of the molecular
      chaperone family of proteins. Each chaperone protein is a complex of seven to
      nine different subunits. A full-length clone of 1.9 kilobases was isolated
      containing an open reading frame of 536 amino acids with a predicted molecular
      weight of 57,736. Comparison with the mouse TCP-1delta revealed 78 and 91%
      homology on the DNA and protein levels, respectively. Northern blot analysis
      disclosed a steady and significant increase in mRNA levels of TCP-1delta after DA
      administration, reaching a peak between 4 and 9 h and declining thereafter.
      Induction of the TCP-1delta protein levels was also observed as a function of DA
      treatment. Overexpression of TCP-1delta in sympathetic neurons accelerated DA
      induced apoptosis; inhibition of TCP-1delta expression in these neurons using
      antisense technology significantly reduced DA-induced neuronal death. These
      findings suggest a functional role for TCP-1delta as a positive mediator of DA
      induced neuronal apoptosis.

PMID- 10954702
TI  - Integrin engagement, the actin cytoskeleton, and c-Src are required for the
      calcitonin-induced tyrosine phosphorylation of paxillin and HEF1, but not for
      calcitonin-induced Erk1/2 phosphorylation.
AB  - We have previously shown that in a HEK-293 cell line that overexpresses the C1a
      isoform of the calcitonin receptor (C1a-HEK), calcitonin induces the tyrosine
      phosphorylation of the focal adhesion-associated proteins HEF1 (a p130(Cas)-like
      docking protein), paxillin, and focal adhesion kinase and that it also stimulates
      the phosphorylation and activation of Erk1 and Erk2. We report here that cell
      attachment to the extracellular matrix, an intact actin cytoskeleton, and c-Src
      are absolutely required for the calcitonin-induced phosphorylation of focal
      adhesion-associated proteins. In contrast to the phosphorylation of paxillin and
      HEF1 in cells attached to fibronectin-coated dishes, calcitonin failed to
      stimulate the phosphorylation of paxillin and HEF1 in suspended cells, in cells
      attached to poly-d-lysine-coated dishes, and in attached cells pretreated with
      the RGD-containing peptide GRGDS. Overexpression of wild-type c-Src increased
      calcitonin-induced paxillin and HEF1 phosphorylation, whereas overexpression of
      kinase-dead Src or Src lacking a functional SH2 domain inhibited the calcitonin
      stimulated tyrosine phosphorylation of these proteins. Overexpression of Src
      lacking the SH3 domain did not affect the calcitonin-induced phosphorylation of
      paxillin and HEF1. In contrast to the regulation of paxillin and HEF1
      phosphorylation, the calcitonin-induced phosphorylation of Erk1 and Erk2 did not
      appear to involve c-Src and was only partially dependent on cell adhesion to the
      extracellular matrix and an intact actin cytoskeleton. Furthermore, inhibition of
      Erk1 and Erk2 phosphorylation had no effect on the calcitonin-induced
      phosphorylation of paxillin and HEF1. Thus, in C1a-HEK cells, the calcitonin
      receptor is coupled to the tyrosine phosphorylation of focal adhesion-associated
      proteins and to Erk1/2 phosphorylation by mechanisms that are in large part
      independent.

PMID- 10954703
TI  - Strain hardening of actin filament networks. Regulation by the dynamic cross
      linking protein alpha-actinin.
AB  - Mechanical stresses applied to the plasma membrane of an adherent cell induces
      strain hardening of the cytoskeleton, i.e. the elasticity of the cytoskeleton
      increases with its deformation. Strain hardening is thought to mediate the
      transduction of mechanical signals across the plasma membrane through the
      cytoskeleton. Here, we describe the strain dependence of a model system
      consisting of actin filaments (F-actin), a major component of the cytoskeleton,
      and the F-actin cross-linking protein alpha-actinin, which localizes along
      contractile stress fibers and at focal adhesions. We show that the amplitude and
      rate of shear deformations regulate the resilience of F-actin networks. At low
      temperatures, for which the lifetime of binding of alpha-actinin to F-actin is
      long, F-actin/alpha-actinin networks exhibit strong strain hardening at short
      time scales and soften at long time scales. For F-actin networks in the absence
      of alpha-actinin or for F-actin/alpha-actinin networks at high temperatures,
      strain hardening appears only at very short time scales. We propose a model of
      strain hardening for F-actin networks, based on both the intrinsic rigidity of F
      actin and dynamic topological constraints formed by the cross-linkers located at
      filaments entanglements. This model offers an explanation for the origin of
      strain hardening observed when shear stresses are applied against the cellular
      membrane.

PMID- 10954704
TI  - Immulectin-2, a lipopolysaccharide-specific lectin from an insect, Manduca sexta,
      is induced in response to gram-negative bacteria.
AB  - A lipopolysaccharide-specific lectin, immulectin-2, was isolated from plasma of
      the tobacco hornworm, Manduca sexta. Immulectin-2 has specificity for xylose,
      glucose, lipopolysaccharide, and mannan. A cDNA clone encoding immulectin-2 was
      isolated from an Escherichia coli-induced M. sexta larval fat body cDNA library.
      The cDNA is 1253 base pairs long, with an open reading frame of 981 base pairs,
      encoding a 327-residue polypeptide. Immulectin-2 is a member of the C-type lectin
      superfamily. It consists of two carbohydrate recognition domains, which is
      similar to the organization of M. sexta immulectin-1. Immulectin-2 was present at
      a constitutively low level in plasma of control larvae and increased 3-4-fold
      after injection of Gram-negative bacteria or lipopolysaccharide. Immulectin-2
      mRNA was detected in fat body of control larvae, and its level increased
      dramatically after injection of E. coli. The concentration of immulectin-2 in
      plasma did not change significantly after injection of Gram-positive bacteria or
      yeast, even though its mRNA level was increased by these treatments. Compared
      with immulectin-1, immulectin-2 has a more restricted specificity for binding to
      Gram-negative bacteria. Immulectin-2 at low physiological concentrations
      agglutinated E. coli in a calcium-dependent manner. It also bound to immobilized
      lipopolysaccharide from E. coli. Binding of immulectin-2 to lipopolysaccharide
      stimulated phenol oxidase activation in plasma. The properties of immulectin-2
      are consistent with its function as a pattern recognition receptor for detection
      and defense against Gram-negative bacterial infection in M. sexta.

PMID- 10954705
TI  - Sterol carrier protein-2 alters high density lipoprotein-mediated cholesterol
      efflux.
AB  - Although sterol carrier protein-2 (SCP-2) participates in the uptake and
      intracellular trafficking of cholesterol, its effect on "reverse cholesterol
      transport" has not been explored. As shown herein, SCP-2 expression inhibited
      high density lipoprotein (HDL)-mediated efflux of [(3)H]cholesterol and
      fluorescent 22-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-23,24-bisnor-5
      cholen-3b-ol (NBD-cholesterol) up to 61 and 157%, respectively. Confocal
      microscopy of living cells allowed kinetic analysis of two intracellular pools of
      HDL-mediated NBD-cholesterol efflux: the highly fluorescent lipid droplet pool
      and the less fluorescent pool outside the lipid droplets, designated the
      cytoplasmic compartment. Both the whole cell and the cytoplasmic compartment
      exhibited two similar kinetic pools, the half-times of which were consistent with
      protein (t(b)(12) near 1 min) and vesicular (t(d)(12) = 10-20 min) mediated
      sterol transfer. Although SCP-2 expression did not alter cytoplasmic sterol pool
      sizes, the rapid t(b)(12) decreased 36%, while the slower t(d)(12) increased
      113%. Lipid droplets also exhibited two kinetic pools of NBD-cholesterol efflux
      but with half-times over 200% shorter than those of the cytoplasmic compartment.
      The lipid droplet slower effluxing pool size and t(d)(12) were increased 48% and
      115%, respectively, in SCP-2-expressing cells. Concomitantly, the level of the
      lipid droplet-specific adipose differentiation-related protein decreased 70%.
      Overall, HDL-mediated sterol efflux from L-cell fibroblasts reflected that of the
      cytoplasmic rather than lipid droplet compartment. SCP-2 differentially modulated
      sterol efflux from the two cytoplasmic pools. However, net efflux was determined
      primarily by inhibition of the slowly effluxing pool rather than by acceleration
      of the rapid protein-mediated pool. Finally, SCP-2 expression also inhibited
      sterol efflux from lipid droplets, an effect related to decreased adipose
      differentiation-related protein, a lipid droplet surface protein that binds
      cholesterol with high affinity.

PMID- 10954706
TI  - Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament
      regulatory protein.
AB  - To elucidate the function of keratins 8 and 18 (K8/18), major components of the
      intermediate filaments of simple epithelia, we searched for K8/18-binding
      proteins by screening a yeast two-hybrid library. We report here that human Mrj,
      a DnaJ/Hsp40 family protein, directly binds to K18. Among the interactions
      between DnaJ/Hsp40 family proteins and various intermediate filament proteins
      that we tested using two-hybrid methods, Mrj specifically interacted with K18.
      Immunostaining with anti-Mrj antibody showed that Mrj colocalized with K8/18
      filaments in HeLa cells. Mrj was immunoprecipitated not only with K18, but also
      with the stress-induced and constitutively expressed heat shock protein Hsp/c70.
      Mrj bound to K18 through its C terminus and interacted with Hsp/c70 via its N
      terminus, which contains the J domain. Microinjection of anti-Mrj antibody
      resulted in the disorganization of K8/18 filaments, without effects on the
      organization of actin filaments and microtubules. Taken together, these results
      suggest that Mrj may play an important role in the regulation of K8/18 filament
      organization as a K18-specific co-chaperone working together with Hsp/c70.

PMID- 10954707
TI  - Functional analysis of two promoters for the human mitochondrial glycerol
      phosphate dehydrogenase gene.
AB  - Mitochondrial glycerol phosphate dehydrogenase (mGPD) is abundant in the normal
      pancreatic insulin cell, but its level is lowered 50% by diabetes. To evaluate
      mGPD expression, we cloned and characterized the 5'-flanking region of the human
      mGPD gene. The gene has two alternative first exons and two promoters. The
      downstream promoter (B) is 10 times more active than the upstream promoter (A) in
      insulin-secreting cells (INS-1) and HeLa cells. Promoter B has higher activity in
      INS-1 than in non-beta cells. Deletion and mutation analysis suggested that a NRF
      2 binding site at -94 to -101 and an E2F binding site at -208 to -215 are
      important regulatory cis elements in promoter B. Gel mobility shift assays
      indicated that the -94 to -101 region binds the NRF-2 protein. When INS-1 cells
      were maintained in the presence of high glucose (25 mm) for 7 days, mGPD was the
      only 1 of 6 enzyme activities lowered (53%). mGPD promoter B activity was reduced
      by 60% in INS-1 cells by the high glucose, but in HepG2 cells and HeLa cells,
      promoter B activity was unchanged or slightly increased. Deletion analysis
      indicated the glucose responsiveness was distributed across the region from -340
      to -260 in promoter B. The results indicate that mGPD gene transcription in the
      beta cell is regulated differently from other cells and that decreased mGPD
      promoter B transcription is at least in part the cause of the decreased beta cell
      mGPD levels in diabetes.

PMID- 10954708
TI  - Two distinct proteins are associated with tetrameric acetylcholinesterase on the
      cell surface.
AB  - In mammalian brain, acetylcholinesterase (AChE) exists mostly as a tetramer of 70
      kDa catalytic subunits that are linked through disulfide bonds to a hydrophobic
      subunit P of approximately 20 kDa. To characterize P, we reduced the disulfide
      bonds in purified bovine brain AChE and sequenced tryptic fragments from bands in
      the 20-kDa region. We obtained sequences belonging to at least two distinct
      proteins: the P protein and another protein that was not disulfide-linked to
      catalytic subunits. Both proteins were recognized in Western blots by antisera
      raised against specific peptides. We cloned cDNA encoding the second protein in a
      cDNA library from bovine substantia nigra and obtained rat and human homologs. We
      call this protein mCutA because of its homology to a bacterial protein (CutA). We
      could not demonstrate a direct interaction between mCutA and AChE in vitro in
      transfected cells. However, in a mouse neuroblastoma cell line that produced
      membrane-bound AChE as an amphiphilic tetramer, the expression of mCutA antisense
      mRNA eliminated cell surface AChE and decreased the level of amphiphilic tetramer
      in cell extracts. mCutA therefore appears necessary for the localization of AChE
      at the cell surface; it may be part of a multicomponent complex that anchors AChE
      in membranes, together with the hydrophobic P protein.

PMID- 10954709
TI  - The Ras/p120 GTPase-activating protein (GAP) interaction is regulated by the p120
      GAP pleckstrin homology domain.
AB  - Pleckstrin homology domains are structurally conserved functional domains that
      can undergo both protein/protein and protein/lipid interactions. Pleckstrin
      homology domains can mediate inter- and intra-molecular binding events to
      regulate enzyme activity. They occur in numerous proteins including many that
      interact with Ras superfamily members, such as p120 GAP. The pleckstrin homology
      domain of p120 GAP is located in the NH(2)-terminal, noncatalytic region of p120
      GAP. Overexpression of the noncatalytic domains of p120 GAP may modulate Ras
      signal transduction pathways. Here, we demonstrate that expression of the
      isolated pleckstrin homology domain of p120 GAP specifically inhibits Ras
      mediated signaling and transformation but not normal cellular growth.
      Furthermore, we show that the pleckstrin homology domain binds the catalytic
      domain of p120 GAP and interferes with the Ras/GAP interaction. Thus, we suggest
      that the pleckstrin homology domain of p120 GAP may specifically regulate the
      interaction of Ras with p120 GAP via competitive intra-molecular binding.

PMID- 10954710
TI  - Epigenetic and genotype-specific effects on the stability of de novo imposed
      methylation patterns in transgenic mice.
AB  - The chloramphenicol acetyltransferase gene under the control of the late E2A
      promoter of adenovirus type 2 (Ad2) was introduced as transgene into the B6D2F1
      mouse strain with mixed genetic background and became extensively de novo
      methylated. The methylation of this pAd2E2AL-CAT (7-1A) transgene was regulated
      in a strain-specific manner apparently depending on the site of integration.
      Transmission of the 7-1A transgene into an inbred DBA/2, 129/sv, or FVB/N genetic
      background led to a significant loss of methylation in the transgene, whereas
      C57BL/6, CB20, and Balb/c backgrounds favored the de novo methylation in very
      specific patterns. The newly established patterns of de novo methylation were
      transmitted to the offspring and remained stable for many generations, regardless
      of the heterozygosity of strain-specific DNA sequences present in these mouse
      strains. Segregation analyses showed a non-mendelian transmission of methylation
      phenotypes and suggested the involvement of dominant modifiers of methylation.
      The genotype-specific modifications of the transgene were followed for 11
      backcross generations. These observations reflect an evolutionarily conserved
      mechanism directed against foreign, e.g. viral or bacterial, DNA at least in the
      chromosomal location of the 7-1A transgene. In seven additional mouse lines
      carrying the same transgene in different chromosomal locations, strain-specific
      alterations of methylation patterns were not observed.

PMID- 10954711
TI  - The BNIP-2 and Cdc42GAP homology domain of BNIP-2 mediates its homophilic
      association and heterophilic interaction with Cdc42GAP.
AB  - We recently showed that BNIP-2 is a putative substrate of the fibroblast growth
      factor receptor tyrosine kinase and it possesses GTPase-activating activity
      toward the small GTPase, Cdc42. The carboxyl terminus of BNIP-2 shares high
      homology to the non-catalytic domain of Cdc42GAP, termed BCH (for BNIP-2 and
      Cdc42GAP homology) domain. Despite the lack of obvious homology to any known
      catalytic domains of GTPase-activating proteins (GAPs), the BCH domain of BNIP-2
      bound Cdc42 and stimulated the GTPase activity via a novel arginine-patch motif
      similar to that employed by one contributing partner in a Cdc42 homodimer. In
      contrast, the BCH domain of Cdc42GAP, although it can bind Cdc42, is
      catalytically inactive. This raises the possibility that these domains might have
      other roles in the cell. Using glutathione S-transferase recombinant proteins,
      immunoprecipitation studies, and yeast two-hybrid assays, it was found that BNIP
      2 and Cdc42GAP could form homo and hetero complexes via their conserved BCH
      domains. Molecular modeling of the BNIP-2 BCH homodimer complex and subsequent
      deletion mutagenesis helped to identify the region (217)RRKMP(221) as the major
      BCH interaction site within BNIP-2. In comparison, deletion of either the
      arginine-patch (235)RRLRK(239) (necessary for GAP activity) or region
      (288)EYV(290) (a Cdc42 binding sequence) had no effect on BCH-BCH interaction.
      Extensive data base searches showed that the BCH domain is highly conserved
      across species. The results suggest that BCH domains of BNIP-2 and Cdc42GAP
      represent a novel protein-protein interaction domain that could potentially
      determine and/or modify the physiological roles of these molecules.

PMID- 10954712
TI  - Recognition of RNA encapsidation signal by the yeast L-A double-stranded RNA
      virus.
AB  - The encapsidation signal of the yeast L-A virus contains a 24-nucleotide stem
      loop structure with a 5-nucleotide loop and an A bulged at the 5' side of the
      stem. The Pol part of the Gag-Pol fusion protein is responsible for encapsidation
      of viral RNA. Opened empty viral particles containing Gag-Pol specifically bind
      to this encapsidation signal in vitro. We found that binding to empty particles
      protected the bulged A and the flanking-two nucleotides from cleavage by Fe(II)
      EDTA-generated hydroxyl radicals. The five nucleotides of the loop sequence
      ((4190)GAUCC(4194)) were not protected. However, T1 RNase protection and in vitro
      mutagenesis experiments indicated that G(4190) is essential for binding. Although
      the sequence of the other four nucleotides of the loop is not essential, data
      from RNase protection and chemical modification experiments suggested that
      C(4194) was also directly involved in binding to empty particles rather than
      indirectly through its potential base pairing with G(4190). These results suggest
      that the Pol domain of Gag-Pol contacts the encapsidation signal at two sites:
      one, the bulged A, and the other, G and C bases at the opening of the loop. These
      two sites are conserved in the encapsidation signal of M1, a satellite RNA of the
      L-A virus.

PMID- 10954713
TI  - Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of
      cells to alkylating agents.
AB  - Mammalian mismatch repair has been implicated in mismatch correction, the
      prevention of mutagenesis and cancer, and the induction of genotoxicity and
      apoptosis. Here, we show that treatment of cells specifically with agents
      inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine
      and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT
      mismatch binding activity in the nucleus. This inducible response occurs
      immediately after alkylation, is long-lasting and dose-dependent, and results
      from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6)
      from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gene
      activity. Cells expressing the DNA repair protein O(6)-methylguanine-DNA
      methyltransferase (MGMT), thus having the ability to repair O(6)-methylguanine,
      showed no translocation of MutSalpha, whereas inhibition of MGMT by O(6)
      benzylguanine provoked the translocation. The results demonstrate that O(6)
      methylguanine lesions are involved in triggering nuclear accumulation of MSH2 and
      MSH6. The finding that treatment of cells with O(6)-methylguanine-generating
      mutagens results in an increase of MutSalpha and GT binding activity in the
      nucleus indicates a novel type of genotoxic stress response.

PMID- 10954715
TI  - X-ray structures of the apo and MgATP-bound states of Dictyostelium discoideum
      myosin motor domain.
AB  - Myosin is the most comprehensively studied molecular motor that converts energy
      from the hydrolysis of MgATP into directed movement. Its motile cycle consists of
      a sequential series of interactions between myosin, actin, MgATP, and the
      products of hydrolysis, where the affinity of myosin for actin is modulated by
      the nature of the nucleotide bound in the active site. The first step in the
      contractile cycle occurs when ATP binds to actomyosin and releases myosin from
      the complex. We report here the structure of the motor domain of Dictyostelium
      discoideum myosin II both in its nucleotide-free state and complexed with MgATP.
      The structure with MgATP was obtained by soaking the crystals in substrate. These
      structures reveal that both the apo form and the MgATP complex are very similar
      to those previously seen with MgATPgammaS and MgAMP-PNP. Moreover, these
      structures are similar to that of chicken skeletal myosin subfragment-1. The
      crystallized protein is enzymatically active in solution, indicating that the
      conformation of myosin observed in chicken skeletal myosin subfragment-1 is
      unable to hydrolyze ATP and most likely represents the pre-hydrolysis structure
      for the myosin head that occurs after release from actin.

PMID- 10954714
TI  - An oncogenic epidermal growth factor receptor signals via a p21-activated kinase
      caldesmon-myosin phosphotyrosine complex.
AB  - Many ligand-independent receptor tyrosine kinases are tumorigenic. The
      biochemical signals that mediate ligand-independent transformation of cells by
      these transmembrane receptors are poorly defined. In this report, we demonstrate
      that a constitutively activated mutant epidermal growth factor receptor (v-ErbB)
      induces the formation of a transformation-specific signaling module that
      complexes with myosin II. The components of this signaling complex include the
      signal adapter proteins Shc, Grb2, and Nck, and tyrosine-phosphorylated forms of
      p21-activated kinase (Pak), caldesmon, and myosin light chain kinase.
      Transformation-specific, tyrosine phosphorylation of Pak enhances the catalytic
      activity of this serine/threonine kinase. Furthermore, the tyrosine
      phosphorylation of Pak is Rho-, but not Ras-, Rac-, or Cdc42-dependent. These
      results demonstrate that a ligand-independent epidermal growth factor receptor
      mutant can transduce oncogenic signals that are distinct from ligand-dependent,
      mitogenic signals. In addition, these data provide evidence for the coupling of
      oncogenic receptor tyrosine kinases with the actomyosin molecular motor. This
      myosin-associated signaling module may mediate some of the biochemical changes of
      myosin found in v-ErbB- transformed fibroblasts, thereby contributing to the
      regulation of the mechanical forces governing cellular adhesion, cytoskeletal
      tension, and, hence, anchorage-independent cell growth.

PMID- 10954716
TI  - Equilibrium and kinetic binding interactions between DNA and a group of novel,
      nonspecific DNA-binding proteins from spores of Bacillus and Clostridium species.
AB  - Binding of alpha/beta-type small acid-soluble spore proteins (SASP) is the major
      determinant of DNA resistance to damage caused by UV radiation, heat, and
      oxidizing agents in spores of Bacillus and Clostridium species. Analysis of
      several alpha/beta-type SASP showed that these proteins have essentially no
      secondary structure in the absence of DNA, but become significantly alpha-helical
      upon binding to double-stranded DNAs or oligonucleotides. Folding of alpha/beta
      type SASP induced by a variety of DNAs and oligonucleotides was measured by CD
      spectroscopy, and this allowed determination of a DNA binding site size of 4 base
      pairs as well as equilibrium binding parameters of the alpha/beta-type SASP-DNA
      interaction. Analysis of the equilibrium binding data further allowed
      determination of both intrinsic binding constants (K) and cooperativity factors
      (omega), as the alpha/beta-type SASP-DNA interaction was significantly
      cooperative, with the degree of cooperativity depending on both the bound DNA and
      the salt concentration. Kinetic analysis of the interaction of one alpha/beta
      type SASP, SspC(Tyr), with DNA indicated that each binding event involves the
      dimerization of SspC(Tyr) monomers at a DNA binding site. The implications of
      these findings for the structure of the alpha/beta-type SASP.DNA complex and the
      physiology of alpha/beta-type SASP degradation during spore germination are
      discussed.

PMID- 10954717
TI  - Mechanism of phosphoanhydride cleavage by baculovirus phosphatase.
AB  - Baculovirus phosphatase (BVP) is a member of the metazoan RNA triphosphatase
      enzyme family that includes the RNA triphosphatase component of the mRNA capping
      apparatus. BVP and other metazoan RNA triphosphatases belong to a superfamily of
      phosphatases that act via the formation and hydrolysis of a covalent cysteinyl
      phosphate intermediate. Here we demonstrate the formation of a BVP phosphoenzyme
      upon reaction with [gamma-(32)P]ATP and identify the linkage as a thiophosphate
      based on its chemical lability. We surmise that the phosphate is linked to
      Cys(119) of BVP because replacement of Cys(119) by alanine or serine abrogates
      phosphoenzyme formation and phosphohydrolase activity. The catalytic cysteine is
      situated within a conserved phosphate-binding loop ((118)HCTHGINRTGY(128)). We
      show that all of the non-aliphatic side chains of the phosphate-binding loop are
      functionally important, insofar as mutants H118A, H121A, N124A, R125A, T126A, and
      Y128A were inactive in gamma phosphate hydrolysis and the T120A mutant was 7% as
      active as wild-type BVP. Structure-activity relationships at the essential
      positions of the phosphate-binding loop were elucidated by conservative
      substitutions. A conserved aspartic acid (Asp(60)) invoked as a candidate general
      acid catalyst was dispensable for phosphohydrolase activity and phosphoenzyme
      formation by BVP. We propose that the low pK(a) of the bridging oxygen of the
      beta phosphate leaving group circumvents a requirement for expulsion by a proton
      donor during attack by cysteine on the gamma phosphorus. In contrast, a conserved
      aspartic acid is essential for the phosphomonoesterase reactions catalyzed by
      protein phosphatases, where the serine or tyrosine leaving groups have a much
      higher pK(a) than does ADP.

PMID- 10954718
TI  - Subsets of human origin recognition complex (ORC) subunits are expressed in non
      proliferating cells and associate with non-ORC proteins.
AB  - The origin recognition complex (ORC) in yeast is a complex of six tightly
      associated subunits essential for the initiation of DNA replication. Human ORC
      subunits are nuclear in proliferating cells and in proliferative tissues like the
      testis, consistent with a role of human ORC in DNA replication. Orc2, Orc3, and
      Orc5 also are detected in non-proliferating cells like cardiac myocytes, adrenal
      cortical cells, and neurons, suggesting an additional role of these proteins in
      non-proliferating cells. Although Orc2-5 co-immunoprecipitate with each other
      under mild extraction conditions, a holo complex of the subunits is difficult to
      detect. When extracted under more stringent extraction conditions, several of the
      subunits co-immunoprecipitate with stoichiometric amounts of other unidentified
      proteins but not with any of the known ORC subunits. The variation in abundance
      of individual ORC subunits (relative to each other) in several tissues,
      expression of some subunits in non-proliferating tissues, and the absence of a
      stoichiometric complex of all the subunits in cell extracts indicate that
      subunits of human ORC in somatic cells might have activities independent of their
      role as a six subunit complex involved in replication initiation. Finally, all
      ORC subunits remain consistently nuclear, and Orc2 is consistently phosphorylated
      through all stages of the cell cycle, whereas Orc1 is selectively phosphorylated
      in mitosis.

PMID- 10954719
TI  - Mutational analysis of op18/stathmin-tubulin-interacting surfaces. Binding
      cooperativity controls tubulin GTP hydrolysis in the ternary complex.
AB  - Oncoprotein 18 (Op18) is a microtubule regulator that forms a ternary complex
      with two tubulin heterodimers. Dispersed regions of Op18 are involved in two-site
      cooperative binding and subsequent modulation of tubulin GTPase activity. Here we
      have analyzed specific determinants of Op18 that govern both stoichiometry and
      positive cooperativity in tubulin binding and consequent stimulatory and
      inhibitory effects on tubulin GTPase activity. The data revealed that the central
      and C-terminal regions of Op18 contain overlapping binding-motifs contacting both
      tubulin heterodimers, suggesting that these regions of Op18 are wedged into the
      previously noted 1-nm gap between the two longitudinally arranged tubulin
      heterodimers. Both the N- and C-terminal flanks adjacent to the central region
      are involved in stabilizing the ternary complex, but only the C-terminal flank
      does so by imposing positive binding cooperativity. Within the C-terminal flank,
      deletion of a 7-amino acid region attenuated positive binding cooperativity and
      resulted in a switch from stimulation to inhibition of tubulin GTP hydrolysis.
      This switch can be explained by attenuated binding cooperativity, because Op18
      under these conditions may block longitudinal contact surfaces of single tubulins
      with consequent interference of tubulin-tubulin interaction-dependent GTP
      hydrolysis. Together, our results suggest that Op18 links two tubulin
      heterodimers via longitudinal contact surfaces to form a ternary GTPase
      productive complex.

PMID- 10954720
TI  - Role of bound zinc in dimer stabilization but not enzyme activity of neuronal
      nitric-oxide synthase.
AB  - Nitric-oxide synthases (NOS) are homodimeric proteins and can form an
      intersubunit Zn(4S) cluster. We have measured zinc bound to NOS purified from pig
      brain (0.6 mol/mol of NOS) and baculovirus-expressed rat neuronal NOS (nNOS)
      (0.49 +/- 0.13 mol/mol of NOS), by on-line gel-filtration/inductively coupled
      plasma mass spectrometry. Cobalt, manganese, molybdenum, nickel, and vanadium
      were all undetectable. Baculovirus-expressed nNOS also bound up to 2. 00 +/- 0.58
      mol of copper/mol of NOS. Diethylenetriaminepentaacetic acid (DTPA) reduced the
      bound zinc to 0.28 +/- 0.07 and the copper to 0.97 +/- 0.24 mol/mol of NOS.
      Desalting of samples into thiol-free buffer did not affect the zinc content but
      completely eliminated the bound copper (</=0.02 mol/mol of NOS). Most (> or =75%)
      of the bound zinc was released from baculovirus-expressed rat nNOS by p
      chloromercuriphenylsulfonic acid (PMPS). PMPS-treated nNOS was strongly (90 +/-
      5%) inactivated. To isolate functional effects of zinc release from other effects
      of PMPS, PMPS-substituted thiols were unblocked by excess reduced thiol in the
      presence of DTPA, which hindered reincorporation of zinc. The resulting enzyme
      contained 0.12 +/- 0.05 mol of zinc but had a specific activity of 426 +/- 46
      nmol of citrulline.mg(-1).min(-1), corresponding to 93 +/- 10% of non-PMPS
      treated controls. PMPS also caused dissociation of nNOS dimers under native
      conditions, an effect that was blocked by the pteridine cofactor
      tetrahydrobiopterin (H(4)biopterin). H(4)biopterin did not affect zinc release.
      Even in the presence of H(4)biopterin, PMPS prevented conversion of NOS dimers to
      an SDS-resistant form. We conclude that zinc binding is a prerequisite for
      formation of SDS-resistant NOS dimers but is not essential for catalysis.

PMID- 10954721
TI  - Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor
      pathway inhibitor-2 on human hepatocellular carcinoma cells.
AB  - We have previously shown that human liver myofibroblasts promote in vitro
      invasion of human hepatocellular carcinoma (HCC) cells through a hepatocyte
      growth factor (HGF)/urokinase/plasmin-dependent mechanism. In this study, we
      demonstrate that myofibroblasts synthesize the serine proteinase inhibitor tissue
      factor pathway inhibitor-2 (TFPI-2). Despite the fact that recombinant TFPI-2
      readily inhibits plasmin, we show that it potentiates HGF-induced invasion of HCC
      cells and is capable of inducing invasion on its own. Furthermore, HCC cells
      stably transfected with a TFPI-2 expression vector became spontaneously invasive.
      HCC cells express tissue factor and specifically factor VII. Addition of an
      antibody to factor VII abolished the pro-invasive effect of TFPI-2. We suggest
      that TFPI-2 induces invasion following binding to a tissue factor-factor VIIa
      complex preformed on HCC cells. Our data thus demonstrate an original mechanism
      of cell invasion that may be specific for liver tumor cells.

PMID- 10954722
TI  - Glycogen synthase kinase-3 beta activity is critical for neuronal death caused by
      inhibiting phosphatidylinositol 3-kinase or Akt but not for death caused by nerve
      growth factor withdrawal.
AB  - Numerous studies reveal that phosphatidylinositol (PI) 3-kinase and Akt protein
      kinase are important mediators of cell survival. However, the survival-promoting
      mechanisms downstream of these enzymes remain uncharacterized. Glycogen synthase
      kinase-3 beta (GSK-3 beta), which is inhibited upon phosphorylation by Akt, was
      recently shown to function during cell death induced by PI 3-kinase inhibitors.
      In this study, we tested whether GSK-3 beta is critical for the death of
      sympathetic neurons caused by the withdrawal of their physiological survival
      factor, the nerve growth factor (NGF). Stimulation with NGF resulted in PI 3
      kinase-dependent phosphorylation of GSK-3 beta and inhibition of its protein
      kinase activity, indicating that GSK-3 beta is targeted by PI 3-kinase/Akt in
      these neurons. Expression of the GSK-3 beta inhibitor Frat1, but not a mutant
      Frat1 protein that does not bind GSK-3 beta, rescued neurons from death caused by
      inhibiting PI 3-kinase. Similarly, expression of Frat1 or kinase-deficient GSK-3
      beta reduced death caused by inhibiting Akt. In NGF-maintained neurons,
      overexpression of GSK-3 beta caused a small but significant decrease in survival.
      However, expression of neither Frat1, kinase-deficient GSK-3 beta, nor GSK-3
      binding protein inhibited NGF withdrawal-induced death. Thus, although GSK-3 beta
      function is required for death caused by inactivation of PI 3-kinase and Akt,
      neuronal death caused by NGF withdrawal can proceed through GSK-3 beta
      independent pathways.

PMID- 10954723
TI  - Positive- and negative-acting Kruppel-like transcription factors bind a
      transforming growth factor beta control element required for expression of the
      smooth muscle cell differentiation marker SM22alpha in vivo.
AB  - Transforming growth factor beta (TGF-beta) is implicated in the regulation of
      smooth muscle cell (SMC) differentiation. We previously identified a novel TGF
      beta control element (TCE) in the promoters of SMC differentiation marker genes,
      including alpha-smooth muscle actin and SM22alpha. In this study, the importance
      of the TCE in regulation of SM22alpha gene expression in vivo was investigated by
      mutating it within the context of a mouse SM22alpha promoter-lacZ transgenic
      construct. Mutation of the TCE completely abolished SM22alpha promoter activity
      in arterial SMCs as well as in developing heart and skeletal muscle. To identify
      the transcription factor(s) binding to the TCE, we performed yeast one-hybrid
      cloning analysis and identified gut-enriched Kruppel-like factor (GKLF). However,
      cotransfection studies in cultured cells showed that GKLF repressed the TGF-beta
      dependent increases in SM22alpha and alpha-smooth muscle actin promoter
      activities. Furthermore, GKLF was not highly expressed in differentiated SMCs in
      vivo, and TGF-beta down-regulated GKLF expression in dedifferentiated cultured
      SMCs. In contrast, overexpression of a related factor (BTEB2) transactivated
      SM22alpha promoter activity. Thus, our findings suggest a reciprocal role for
      related Kruppel-like transcription factors in the regulation of SMC
      differentiation through a TCE-dependent mechanism.

PMID- 10954724
TI  - Steady state kinetic model for the binding of substrates and allosteric effectors
      to Escherichia coli phosphoribosyl-diphosphate synthase.
AB  - A steady state kinetic investigation of the P(i) activation of 5-phospho-d
      ribosyl alpha-1-diphosphate synthase from Escherichia coli suggests that P(i) can
      bind randomly to the enzyme either before or after an ordered addition of free
      Mg(2+) and substrates. Unsaturation with ribose 5-phosphate increased the
      apparent cooperativity of P(i) activation. At unsaturating P(i) concentrations
      partial substrate inhibition by ribose 5-phosphate was observed. Together these
      results suggest that saturation of the enzyme with P(i) directs the subsequent
      ordered binding of Mg(2+) and substrates via a fast pathway, whereas saturation
      with ribose 5-phosphate leads to the binding of Mg(2+) and substrates via a slow
      pathway where P(i) binds to the enzyme last. The random mechanism for P(i)
      binding was further supported by studies with competitive inhibitors of Mg(2+),
      MgATP, and ribose 5-phosphate that all appeared noncompetitive when varying P(i)
      at either saturating or unsaturating ribose 5-phosphate concentrations.
      Furthermore, none of the inhibitors induced inhibition at increasing P(i)
      concentrations. Results from ADP inhibition of P(i) activation suggest that these
      effectors compete for binding to a common regulatory site.

PMID- 10954725
TI  - FlaA1, a new bifunctional UDP-GlcNAc C6 Dehydratase/ C4 reductase from
      Helicobacter pylori.
AB  - FlaA1 is a small soluble protein of unknown function in Helicobacter pylori. It
      has homologues that are essential for the virulence of numerous medically
      relevant bacteria. FlaA1 was overexpressed as a histidine-tagged protein and
      purified to homogeneity by nickel chelation and cation exchange chromatography.
      Spectrophotometric assays, capillary electrophoresis, and mass spectrometry
      analyses showed that FlaA1 is a novel bifunctional C(6) dehydratase/C(4)
      reductase specific for UDP-GlcNAc. It converts UDP-GlcNAc into a UDP-4-keto-6
      methyl-GlcNAc intermediate, which is stereospecifically reduced into UDP-QuiNAc.
      Substrate conversions as high as 80% were obtained at equilibrium. The K(m) and
      V(max) for UDP-GlcNAc were 159 microm and 65 pmol/min, respectively. No exogenous
      cofactor was required to obtain full activity of FlaA1. Additional NADH was only
      used with poor efficiency for the reduction step. The biochemical
      characterization of FlaA1 is important for the elucidation of biosynthetic
      pathways that lead to the formation of 2,6-deoxysugars in medically relevant
      bacteria. It establishes unambiguously the first step of the pathway and provides
      the means of preparing the substrate UDP-QuiNAc, which is necessary for the study
      of downstream enzymes.

PMID- 10954726
TI  - Very long-chain acyl-CoA synthetases. Human "bubblegum" represents a new family
      of proteins capable of activating very long-chain fatty acids.
AB  - Activation by thioesterification to coenzyme A is a prerequisite for most
      reactions involving fatty acids. Enzymes catalyzing activation, acyl-CoA
      synthetases, have been classified by their chain length specificities. The most
      recently identified family is the very long-chain acyl-CoA synthetases (VLCS).
      Although several members of this group are capable of activating very long-chain
      fatty acids (VLCFA), one is a bile acid-CoA synthetase, and others have been
      characterized as fatty acid transport proteins. It was reported that the
      Drosophila melanogaster mutant bubblegum (BGM) had elevated VLCFA and that the
      product of the defective gene had sequence homology to acyl-CoA synthetases.
      Therefore, we cloned full-length cDNA for a human homolog of BGM, and we
      investigated the properties of its protein product, hsBG, to determine whether it
      had VLCS activity. Northern blot analysis showed that hsBG is expressed primarily
      in brain. Compared with vector-transfected cells, COS-1 cells expressing hsBG had
      increased acyl-CoA synthetase activity with either long-chain fatty acid (2.4
      fold) or VLCFA (2.6-fold) substrates. Despite this increased VLCFA activation,
      hsBG-expressing cells did not have increased rates of VLCFA degradation. Confocal
      microscopy showed that hsBG had a cytoplasmic localization in some COS-1 cells
      expressing the protein, whereas it appeared to associate with plasma membrane in
      others. Fractionation of these cells revealed that most of the hsBG-dependent
      acyl-CoA synthetase activity was soluble and not membrane-bound. Immunoaffinity
      purified hsBG from transfected COS-1 cells was enzymatically active. hsBG and
      hsVLCS are only 15% identical, and comparison with sequences of two conserved
      motifs from all known families of acyl-CoA synthetases revealed that hsBG along
      with the D. melanogaster and murine homologs comprise a new family of acyl-CoA
      synthetases. Thus, two protein families are now known that contain enzymes
      capable of activating VLCFA. Because hsBG is expressed in brain but previously
      described VLCSs were not highly expressed in this organ, hsBG may play a central
      role in brain VLCFA metabolism and myelinogenesis.

PMID- 10954727
TI  - Lysophosphatidic acid-induced Ca2+ mobilization requires intracellular
      sphingosine 1-phosphate production. Potential involvement of endogenous EDG-4
      receptors.
AB  - Lysophosphatidic acid (LPA)-mediated Ca(2+) mobilization in human SH-SY5Y
      neuroblastoma cells does not involve either inositol 1,4, 5-trisphosphate
      (Ins(1,4,5)P(3))- or ryanodine-receptor pathways, but is sensitive to inhibitors
      of sphingosine kinase. This present study identifies Edg-4 as the receptor
      subtype involved and investigates the presence of a Ca(2+) signaling cascade
      based upon the lipid second messenger molecule, sphingosine 1-phosphate. Both LPA
      and direct G-protein activation increase [(3)H]sphingosine 1-phosphate levels in
      SH-SY5Y cells. Measurements of (45)Ca(2+) release in premeabilized SH-SY5Y cells
      indicates that sphingosine 1-phosphate, sphingosine, and
      sphingosylphosphorylcholine, but not N-acetylsphingosine are capable of
      mobilizing intracellular Ca(2+). Furthermore, the effect of sphingosine was
      attenuated by the sphingosine kinase inhibitor dimethylsphingosine, or removal of
      ATP. Confocal microscopy demonstrated that LPA stimulated intracellular Ca(2+)
      "puffs," which resulted from an interaction between the sphingolipid Ca(2+)
      release pathway and Ins(1,4,5)P(3) receptors. Down-regulation of Ins(1,4,5)P(3)
      receptors uncovered a Ca(2+) response to LPA, which was manifest as a progressive
      increase in global cellular Ca(2+) with no discernible foci. We suggest that
      activation of an LPA-sensitive Edg-4 receptor solely utilizes the production of
      intracellular sphingosine 1-phosphate to stimulate Ca(2+) mobilization in SH-SY5Y
      cells. Unlike traditional Ca(2+) release processes, this novel pathway does not
      require the progressive recruitment of elementary Ca(2+) events.

PMID- 10954728
TI  - Regulation of yeast ectoapyrase ynd1p activity by activator subunit Vma13p of
      vacuolar H+-ATPase.
AB  - CD39-like ectoapyrases are involved in protein and lipid glycosylation in the
      Golgi lumen of Saccharomyces cerevisiae. By using a two-hybrid screen, we found
      that an activator subunit (Vma13p) of yeast vacuolar H(+)-ATPase (V-ATPase) binds
      to the cytoplasmic domain of Ynd1p, a yeast ectoapyrase. Interaction of Ynd1p
      with Vma13p was demonstrated by direct binding and co-immunoprecipitation.
      Surprisingly, the membrane-bound ADPase activity of Ynd1p in a vma13Delta mutant
      was drastically increased compared with that of Ynd1p in VMA13 cells. A similar
      increase in the apyrase activity of Ynd1p was found in a vma1Delta mutant, in
      which the catalytic subunit A of V-ATPase is missing, and the membrane peripheral
      subunits including Vma13p are dissociated from the membranes. However, the E286Q
      mutant of VMA1, which assembles inactive V-ATPase complex including Vma13p in the
      membrane, retained wild type levels of Ynd1p activity, demonstrating that the
      presence of Vma13p rather than the function of V-ATPase in the membrane represses
      Ynd1p activity. These results suggest that association of Vma13p with the
      cytoplasmic domain of Ynd1p regulates its apyrase activity in the Golgi lumen.

PMID- 10954729
TI  - Interactions of DNA helicases with damaged DNA: possible biological consequences.

PMID- 10954730
TI  - Dynamical principles in biological processes: a model of charge migration in
      proteins and DNA.
AB  - The generalized master equations (GMEs) that contain multiple time scales have
      been derived quantum mechanically. The GME method has then been applied to a
      model of charge migration in proteins that invokes the hole hopping between local
      amino acid sites driven by the torsional motions of the floppy backbones. This
      model is then applied to analyze the experimental results for sequence-dependent
      long-range hole transport in DNA reported by Meggers et al. [Meggers, E., Michel
      Beyerle, M. E., & Giese, B. (1998) J. Am. Chem. Soc. 120, 12950-12955]. The model
      has also been applied to analyze the experimental results of femtosecond dynamics
      of DNA-mediated electron transfer reported by Zewail and co-workers [Wan, C.,
      Fiebig, T., Kelley, S. O., Treadway, C. R., Barton, J. K. & Zewail, A. H. (1999)
      Proc. Natl. Acad. Sci. USA 96, 6014-6019]. The initial events in the dynamics of
      protein folding have begun to attract attention. The GME obtained in this paper
      will be applicable to this problem.

PMID- 10954732
TI  - Statistical significance of protein structure prediction by threading.
AB  - In this study, we estimate the statistical significance of structure prediction
      by threading. We introduce a single parameter epsilon that serves as a universal
      measure determining the probability that the best alignment is indeed a native
      like analog. Parameter epsilon takes into account both length and composition of
      the query sequence and the number of decoys in threading simulation. It can be
      computed directly from the query sequence and potential of interactions,
      eliminating the need for sequence reshuffling and realignment. Although our
      theoretical analysis is general, here we compare its predictions with the results
      of gapless threading. Finally we estimate the number of decoys from which the
      native structure can be found by existing potentials of interactions. We discuss
      how this analysis can be extended to determine the optimal gap penalties for any
      sequence-structure alignment (threading) method, thus optimizing it to maximum
      possible performance.

PMID- 10954731
TI  - Conservation of early odontogenic signaling pathways in Aves.
AB  - Teeth have been missing from birds (Aves) for at least 60 million years. However,
      in the chick oral cavity a rudiment forms that resembles the lamina stage of the
      mammalian molar tooth germ. We have addressed the molecular basis for this
      secondary loss of tooth formation in Aves by analyzing in chick embryos the
      status of molecular pathways known to regulate mouse tooth development. Similar
      to the mouse dental lamina, expression of Fgf8, Pitx2, Barx1, and Pax9 defines a
      potential chick odontogenic region. However, the expression of three molecules
      involved in tooth initiation, Bmp4, Msx1, and Msx2, are absent from the
      presumptive chick dental lamina. In chick mandibles, exogenous bone morphogenetic
      protein (BMP) induces Msx expression and together with fibroblast growth factor
      promotes the development of Sonic hedgehog expressing epithelial structures.
      Distinct epithelial appendages also were induced when chick mandibular epithelium
      was recombined with a tissue source of BMPs and fibroblast growth factors, chick
      skin mesenchyme. These results show that, although latent, the early signaling
      pathways involved in odontogenesis remain inducible in Aves and suggest that loss
      of odontogenic Bmp4 expression may be responsible for the early arrest of tooth
      development in living birds.

PMID- 10954734
TI  - Novel folded protein domains generated by combinatorial shuffling of polypeptide
      segments.
AB  - It has been proposed that the architecture of protein domains has evolved by the
      combinatorial assembly and/or exchange of smaller polypeptide segments. To
      investigate this proposal, we fused DNA encoding the N-terminal half of a beta
      barrel domain (from cold shock protein CspA) with fragmented genomic Escherichia
      coli DNA and cloned the repertoire of chimeric polypeptides for display on
      filamentous bacteriophage. Phage displaying folded polypeptides were selected by
      proteolysis; in most cases the protease-resistant chimeric polypeptides comprised
      genomic segments in their natural reading frames. Although the genomic segments
      appeared to have no sequence homologies with CspA, one of the originating
      proteins had the same fold as CspA, but another had a different fold. Four of the
      chimeric proteins were expressed as soluble polypeptides; they formed monomers
      and exhibited cooperative unfolding. Indeed, one of the chimeric proteins
      contained a set of very slowly exchanging amides and proved more stable than CspA
      itself. These results indicate that native-like proteins can be generated
      directly by combinatorial segment assembly from nonhomologous proteins, with
      implications for theories of the evolution of new protein folds, as well as
      providing a means of creating novel domains and architectures in vitro.

PMID- 10954733
TI  - Insulin-like growth factor 1 regulates developing brain glucose metabolism.
AB  - The brain has enormous anabolic needs during early postnatal development. This
      study presents multiple lines of evidence showing that endogenous brain insulin
      like growth factor 1 (Igf1) serves an essential, insulin-like role in promoting
      neuronal glucose utilization and growth during this period. Brain 2-deoxy-d- [1
      (14)C]glucose uptake parallels Igf1 expression in wild-type mice and is
      profoundly reduced in Igf1-/- mice, particularly in those structures where Igf1
      is normally most highly expressed. 2-Deoxy-d- [1-(14)C]glucose is significantly
      reduced in synaptosomes prepared from Igf1-/- brains, and the deficit is
      corrected by inclusion of Igf1 in the incubation medium. The serine/threonine
      kinase Akt/PKB is a major target of insulin-signaling in the regulation of
      glucose transport via the facilitative glucose transporter (GLUT4) and glycogen
      synthesis in peripheral tissues. Phosphorylation of Akt and GLUT4 expression are
      reduced in Igf1-/- neurons. Phosphorylation of glycogen synthase kinase 3beta and
      glycogen accumulation also are reduced in Igf1-/- neurons. These data support the
      hypothesis that endogenous brain Igf1 serves an anabolic, insulin-like role in
      developing brain metabolism.

PMID- 10954735
TI  - Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes.
AB  - Plasmodium falciparum requires glucose as its energy source to multiply within
      erythrocytes but is separated from plasma by multiple membrane systems. The
      mechanism of delivery of substrates such as glucose to intraerythrocytic
      parasites is unclear. We have developed a system for robust functional expression
      in Xenopus oocytes of the P. falciparum asexual stage hexose permease, PfHT1, and
      have analyzed substrate specificities of PfHT1. We show that PfHT1 (a high
      affinity glucose transporter, K(m) approximately 1.0 mM) also transports fructose
      (K(m) approximately 11.5 mM). Fructose can replace glucose as an energy source
      for intraerythrocytic parasites. PfHT1 binds fructose in a furanose conformation
      and glucose in a pyranose form. Fructose transport by PfHT1 is ablated by
      mutation of a single glutamine residue, Q169, which is predicted to lie within
      helix 5 of the hexose permeation pathway. Glucose transport in the Q169N mutant
      is preserved. Comparison in oocytes of transport properties of PfHT1 and human
      facilitative glucose transporter (GLUT)1, an archetypal mammalian hexose
      transporter, combined with studies on cultured P. falciparum, has clarified
      hexose permeation pathways in infected erythrocytes. Glucose and fructose enter
      erythrocytes through separate permeation pathways. Our studies suggest that both
      substrates enter parasites via PfHT1.

PMID- 10954736
TI  - A Stat3-interacting protein (StIP1) regulates cytokine signal transduction.
AB  - Genetic and biochemical studies have led to the identification of the Stat3
      Interacting Protein StIP1. The preferential association of StIP1 with inactive
      (i.e., unphosphorylated) Stat3 suggests that it may contribute to the regulation
      of Stat3 activation. Consistent with this possibility, StIP1 also exhibits an
      affinity for members of the Janus kinase family. Overexpression of the Stat3
      binding domain of StIP1 blocks Stat3 activation, nuclear translocation, and Stat3
      dependent induction of a reporter gene. These studies indicate that StIP1
      regulates the ligand-dependent activation of Stat3, potentially by serving as a
      scaffold protein that promotes the interaction between Janus kinases and their
      Stat3 substrate. The ability of StIP1 to associate with several additional
      members of the signal transducer and activator of transcription family suggests
      that StIP1 may serve a broader role in cytokine-signaling events.

PMID- 10954737
TI  - Human mesothelial cells are unusually susceptible to simian virus 40-mediated
      transformation and asbestos cocarcinogenicity.
AB  - Mesothelioma, a malignancy associated with asbestos, has been recently linked to
      simian virus 40 (SV40). We found that infection of human mesothelial cells by
      SV40 is very different from the semipermissive infection thought to be
      characteristic of human cells. Mesothelial cells are uniformly infected but not
      lysed by SV40, a mechanism related to p53, and undergo cell transformation at an
      extremely high rate. Exposure of mesothelial cells to asbestos complemented SV40
      mutants in transformation. Our data provide a mechanistic explanation for the
      ability of SV40 to transform mesothelial cells preferentially and indicate that
      asbestos and SV40 may be cocarcinogens.

PMID- 10954738
TI  - Protection against hemorrhagic shock in mice genetically deficient in poly(ADP
      ribose)polymerase.
AB  - Hemorrhagic shock (HS) and resuscitation leads to widespread production of
      oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has
      been shown to contribute to cell necrosis and organ failure in various disease
      conditions associated with oxidative stress. We tested the hypothesis whether
      PARP activation plays a role in the multiple organ dysfunction complicating HS
      and resuscitation in a murine model of HS and resuscitation by using mice
      genetically deficient in PARP (PARP(-/-)) and their wild-type littermates
      (PARP(+/+)). Animals were bled to a mean blood pressure of 45 mmHg (1 mmHg = 133
      Pa) and resuscitated after 45 min with isotonic saline (2x volume of shed blood).
      There was a massive activation of PARP, detected by poly(ADP-ribose)
      immunohistochemistry, which localized to the areas of the most severe intestinal
      injury, i.e., the necrotic epithelial cells at the tip of the intestinal villi,
      and colocalized with tyrosine nitration, an index of peroxynitrite generation.
      Intestinal PARP activation resulted in gut hyperpermeability, which developed in
      PARP(+/+) but not PARP(-/-) mice. PARP(-/-) mice were also protected from the
      rapid decrease in blood pressure after resuscitation and showed an increased
      survival time, as well as reduced lung neutrophil sequestration. The beneficial
      effects of PARP suppression were not related to a modulation of the NO pathway
      nor to a modulation of signaling through IL-6, which similarly increased in both
      PARP(+/+) and PARP(-/-) mice exposed to HS. We propose that PARP activation and
      associated cell injury (necrosis) plays a crucial role in the intestinal injury,
      cardiovascular failure, and multiple organ damage associated with resuscitated
      HS.

PMID- 10954739
TI  - Immunoassays with rolling circle DNA amplification: a versatile platform for
      ultrasensitive antigen detection.
AB  - We describe an adaptation of the rolling circle amplification (RCA) reporter
      system for the detection of protein Ags, termed "immunoRCA. " In immunoRCA, an
      oligonucleotide primer is covalently attached to an Ab; thus, in the presence of
      circular DNA, DNA polymerase, and nucleotides, amplification results in a long
      DNA molecule containing hundreds of copies of the circular DNA sequence that
      remain attached to the Ab and that can be detected in a variety of ways. Using
      immunoRCA, analytes were detected at sensitivities exceeding those of
      conventional enzyme immunoassays in ELISA and microparticle formats. The signal
      amplification afforded by immunoRCA also enabled immunoassays to be carried out
      in microspot and microarray formats with exquisite sensitivity. When Ags are
      present at concentrations down to fM levels, specifically bound Abs can be scored
      by counting discrete fluorescent signals arising from individual Ag-Ab complexes.
      Multiplex immunoRCA also was demonstrated by accurately quantifying Ags mixed in
      different ratios in a two-color, single-molecule-counting assay on a glass slide.
      ImmunoRCA thus combines high sensitivity and a very wide dynamic range with an
      unprecedented capability for single molecule detection. This Ag-detection method
      is of general applicability and is extendable to multiplexed immunoassays that
      employ a battery of different Abs, each labeled with a unique oligonucleotide
      primer, that can be discriminated by a color-coded visualization system.
      ImmunoRCA-profiling based on the simultaneous quantitation of multiple Ags should
      expand the power of immunoassays by exploiting the increased information content
      of ratio-based expression analysis.

PMID- 10954740
TI  - A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates
      function by forming alternative structures.
AB  - DsrA is an 87-nucleotide regulatory RNA of Escherichia coli that acts in trans by
      RNA-RNA interactions with two different mRNAs, hns and rpoS. DsrA has opposite
      effects on these transcriptional regulators. H-NS levels decrease, whereas RpoS
      (final sigma(s)) levels increase. Here we show that DsrA enhances hns mRNA
      turnover yet stabilizes rpoS mRNA, either directly or via effects on translation.
      Computational and RNA footprinting approaches led to a refined structure for
      DsrA, and a model in which DsrA interacts with the hns mRNA start and stop codon
      regions to form a coaxial stack. Analogous bipartite interactions exist in
      eukaryotes, albeit with different regulatory consequences. In contrast, DsrA base
      pairs in discrete fashion with the rpoS RNA translational operator. Thus,
      different structural configurations for DsrA lead to opposite regulatory
      consequences for target RNAs.

PMID- 10954741
TI  - Binding site of brefeldin A at the interface between the small G protein ADP
      ribosylation factor 1 (ARF1) and the nucleotide-exchange factor Sec7 domain.
AB  - Sec7 domains (Sec7d) catalyze the exchange of guanine nucleotide on ARFs. Recent
      studies indicated that brefeldin A (BFA) inhibits Sec7d-catalyzed nucleotide
      exchange on ARF1 in an uncompetitive manner by trapping an early intermediate of
      the reaction: a complex between GDP-bound ARF1 and Sec7d. Using (3)H-labeled BFA,
      we show that BFA binds to neither isolated Sec7d nor isolated ARF1-GDP, but binds
      to the transitory Sec7d-ARF1-GDP complex and stabilizes it. Two pairs of residues
      at positions 190-191 and 198-208 (Arno numbering) in Sec7d contribute equally to
      the stability of BFA binding, which is also sensitive to mutation of H80 in ARF1.
      The catalytic glutamic (E156) residue of Sec7d is not necessary for BFA binding.
      In contrast, BFA does not bind to the intermediate catalytic complex between
      nucleotide-free ARF1 and Sec7d. These results suggest that, on initial docking
      steps between ARF1-GDP and Sec7d, BFA inserts like a wedge between the switch II
      region of ARF1-GDP and a surface encompassing residues 190-208, at the border of
      the characteristic hydrophobic groove of Sec7d. Bound BFA would prevent the
      switch regions of ARF1-GDP from reorganizing and forming tighter contacts with
      Sec7d and thereby would maintain the bound GDP of ARF1 at a distance from the
      catalytic glutamic finger of Sec7d.

PMID- 10954742
TI  - Human interleukin-10-related T cell-derived inducible factor: molecular cloning
      and functional characterization as an hepatocyte-stimulating factor.
AB  - IL-10-related T cell-derived inducible factor (IL-TIF or IL-21) is a new cytokine
      structurally related to IL-10 and originally identified in the mouse as a gene
      induced by IL-9 in T cells and mast cells. Here, we report the cloning of the
      human IL-TIF cDNA, which shares 79% amino acid identity with mouse IL-TIF and 25%
      identity with human IL-10. Recombinant human IL-TIF was found to activate signal
      transducer and activator of transcription factors-1 and -3 in several hepatoma
      cell lines. IL-TIF stimulation of HepG2 human hepatoma cells up-regulated the
      production of acute phase reactants such as serum amyloid A, alpha1
      antichymotrypsin, and haptoglobin. Although IL-10 and IL-TIF have distinct
      activities, antibodies directed against the beta chain of the IL-10 receptor
      blocked the induction of acute phase reactants by IL-TIF, indicating that this
      chain is a common component of the IL-10 and IL-TIF receptors. Similar acute
      phase reactant induction was observed in mouse liver upon IL-TIF injection, and
      IL-TIF expression was found to be rapidly increased after lipopolysaccharide
      (LPS) injection, suggesting that this cytokine contributes to the inflammatory
      response in vivo.

PMID- 10954743
TI  - Skeletal muscle sodium current is reduced in hypokalemic periodic paralysis.

PMID- 10954744
TI  - Using O2 to probe membrane immersion depth by 19F NMR.
AB  - A fluorinated detergent, CF(3)(CF(2))(5)C(2)H(4)-O-maltose, was reconstituted
      into a lipid bilayer model membrane system to demonstrate the feasibility of
      determining solvent accessibility and membrane immersion depth of each
      fluorinated group by (19)F NMR. Apolar oxygen, which is known to partition with
      an increasing concentration gradient toward the hydrophobic membrane interior,
      exhibits a range of paramagnetic relaxation effects on (19)F nuclei, depending on
      its depth in the membrane. This effect, which is predominately associated with
      spin-lattice relaxation rates (R(1)) and chemical shifts, can be amplified
      greatly with minimal line broadening by increasing the partial pressure of O(2)
      at least 100-fold (i.e., P(O(2)) greater than 20 bar). The differences of
      longitudinal relaxation rates at 20 bar of oxygen pressure to those under ambient
      pressure (R(1)(20bar) - R(1)(0)) are largest for those fluorine groups expected
      to be most deeply buried in the membrane bilayer. This result contrasts with the
      reverse trend, which is observed on addition of a membrane surface-associated
      paramagnetic species, 4-(N,N-dimethyl-N-hexadecyl) ammonium-2,2,6,6
      tetramethylpiperidine-1-oxyl iodide (CAT-16) at ambient pressures. Thus,
      differential relaxation rates may be observed in (19)F-labeled membrane
      associated molecules resulting from the addition of apolar oxygen under high
      pressure. The results demonstrate that the degree of solvent accessibility and
      membrane immersion depth of specific fluorinated species in membrane-associated
      macromolecules can be probed by (19)F NMR.

PMID- 10954745
TI  - Multiple independent origins of Shigella clones of Escherichia coli and
      convergent evolution of many of their characteristics.
AB  - The evolutionary relationships of 46 Shigella strains representing each of the
      serotypes belonging to the four traditional Shigella species (subgroups),
      Dysenteriae, Flexneri, Boydii, and Sonnei, were determined by sequencing of eight
      housekeeping genes in four regions of the chromosome. Analysis revealed a very
      similar evolutionary pattern for each region. Three clusters of strains were
      identified, each including strains from different subgroups. Cluster 1 contains
      the majority of Boydii and Dysenteriae strains (B1-4, B6, B8, B10, B14, and B18;
      and D3-7, D9, and D11-13) plus Flexneri 6 and 6A. Cluster 2 contains seven Boydii
      strains (B5, B7, B9, B11, B15, B16, and B17) and Dysenteriae 2. Cluster 3
      contains one Boydii strain (B12) and the Flexneri serotypes 1-5 strains. Sonnei
      and three Dysenteriae strains (D1, D8, and D10) are outside of the three main
      clusters but, nonetheless, are clearly within Escherichia coli. Boydii 13 was
      found to be distantly related to E. coli. Shigella strains, like the other
      pathogenic forms of E. coli, do not have a single evolutionary origin, indicating
      convergent evolution of Shigella phenotypic properties. We estimate the three
      main Shigella clusters to have evolved within the last 35,000 to 270,000 years,
      suggesting that shigellosis was one of the early infectious diseases of humans.

PMID- 10954746
TI  - Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the
      transport and metabolism of nitric oxide by hemoglobin in the human circulation.
AB  - To quantify the reactions of nitric oxide (NO) with hemoglobin under
      physiological conditions and to test models of NO transport on hemoglobin, we
      have developed an assay to measure NO-hemoglobin reaction products in normal
      volunteers, under basal conditions and during NO inhalation. NO inhalation
      markedly raised total nitrosylated hemoglobin levels, with a significant arterial
      venous gradient, supporting a role for hemoglobin in the transport and delivery
      of NO. The predominant species accounting for this arterial-venous gradient is
      nitrosyl(heme)hemoglobin. NO breathing increases S-nitrosation of hemoglobin beta
      chain cysteine 93, however only to a fraction of the level of
      nitrosyl(heme)hemoglobin and without a detectable arterial-venous gradient. A
      strong correlation between methemoglobin and plasma nitrate formation was
      observed, suggesting that NO metabolism is a primary physiological cause of
      hemoglobin oxidation. Our results demonstrate that NO-heme reaction pathways
      predominate in vivo, NO binding to heme groups is a rapidly reversible process,
      and S-nitrosohemoglobin formation is probably not a primary transport mechanism
      for NO but may facilitate NO release from heme.

PMID- 10954747
TI  - Gel catalysts that switch on and off.
AB  - We report development of a polymer gel with a catalytic activity that can be
      switched on and off when the solvent composition is changed. The gel consists of
      two species of monomers. The major component, N-isopropylacrylamide, makes the
      gel swell and shrink in response to a change in composition of ethanol/water
      mixtures. The minor component, vinylimidazole, which is capable of catalysis, is
      copolymerized into the gel network. The reaction rate for catalytic hydrolysis of
      p-nitrophenyl caprylate was small when the gel was swollen. In contrast, when the
      gel was shrunken, the reaction rate increased 5 times. The activity changes
      discontinuously as a function of solvent composition, thus the catalysis can be
      switched on and off by an infinitesimal change in solvent composition. The
      kinetics of catalysis by the gel in the shrunken state is well described by the
      Michaelis-Menten formula, indicating that the absorption of the substrate by the
      hydrophobic environment created by the N-isopropylacrylamide polymer in the
      shrunken gel is responsible for enhancement of catalytic activity. In the swollen
      state, the rate vs. active site concentration is linear, indicating that the
      substrate absorption is not a primary factor determining the kinetics. Catalytic
      activity of the gel is studied for substrates with various alkyl chain lengths;
      of those studied the switching effect is most pronounced for p-nitrophenyl
      caprylate.

PMID- 10954748
TI  - Loss of signaling through the G protein, Gz, results in abnormal platelet
      activation and altered responses to psychoactive drugs.
AB  - Heterotrimeric G proteins mediate the earliest step in cell responses to external
      events by linking cell surface receptors to intracellular signaling pathways.
      G(z) is a member of the G(i) family of G proteins that is prominently expressed
      in platelets and brain. Here, we show that deletion of the alpha subunit of G(z)
      in mice: (i) impairs platelet aggregation by preventing the inhibition of cAMP
      formation normally seen at physiologic concentrations of epinephrine, and (ii)
      causes the mice to be more resistant to fatal thromboembolism. Loss of G(zalpha)
      also results in greatly exaggerated responses to cocaine, reduces the analgesic
      effects of morphine, and abolishes the effects of widely used antidepressant
      drugs that act as catecholamine reuptake inhibitors. These changes occur despite
      the presence of other G(ialpha) family members in the same cells and are not
      accompanied by detectable compensatory changes in the level of expression of
      other G protein subunits. Therefore, these results provide insights into receptor
      selectivity among G proteins and a model for understanding platelet function and
      the effects of psychoactive drugs.

PMID- 10954749
TI  - Calcium-triggered acrosomal exocytosis in human spermatozoa requires the
      coordinated activation of Rab3A and N-ethylmaleimide-sensitive factor.
AB  - The acrosome reaction of spermatozoa is a complex, calcium-dependent, regulated
      exocytosis. Fusion at multiple sites between the outer acrosomal membrane and the
      cell membrane causes the release of the acrosomal contents and the loss of the
      membranes surrounding the acrosome. However, very little is known about the
      molecules that mediate and regulate this unique fusion process. Here, we show
      that N-ethylmaleimide-sensitive factor (NSF), a protein essential for most fusion
      events, is present in the acrosome of several mammalian spermatozoa. Moreover, we
      demonstrate that calcium-dependent exocytosis of permeabilized sperm requires
      active NSF. Previously, we have shown that the addition of the active (GTP-bound)
      form of the small GTPase Rab3A triggers exocytosis in permeabilized spermatozoa.
      In the present report we show that Rab3A is necessary for calcium-dependent
      exocytosis. The activation of Rab3A protects NSF from N-ethylmaleimide inhibition
      and precludes the exchange of the endogenous protein with recombinant dominant
      negative mutants of NSF. Furthermore, Rab3A activation of acrosomal exocytosis
      requires active NSF. Our results suggest that, upon calcium stimulation, Rab3A
      switches to its active GTP-bound form, triggering the formation of a protein
      complex in which NSF is protected. This process is suggested to be an essential
      part of the molecular mechanism of membrane fusion leading to the release of the
      acrosomal contents.

PMID- 10954750
TI  - Multiple benefits of multiple mating in guppies.
AB  - The rewards of promiscuity for males are undisputed. But why should a female mate
      promiscuously, particularly when her partners offer no resources other than sperm
      and increase her chances of succumbing to predation or disease? This question has
      been hotly debated but at present remains largely unresolved [Jennions, M. D. &
      Petrie, M. (2000) Biol. Rev. 75, 21-64]. One possibility is that females exploit
      postcopulatory mechanisms, such as sperm competition, to increase both the
      quality and quantity of their offspring. In this paper, we use the Trinidadian
      guppy, a species with a resource-free mating system, to test the hypothesis that
      females gain multiple benefits from multiple mating. Our results indicate that
      multiply mated females secure substantive advantages: They have shorter gestation
      times and larger broods, and they produce offspring with better developed
      schooling abilities and escape responses than their singly mated counterparts.

PMID- 10954751
TI  - Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei.
AB  - Trypanosoma brucei, the protozoan parasite responsible for sleeping sickness,
      evades the immune response of mammalian hosts and digestion in the gut of the
      insect vector by means of its coat proteins tethered to the cell surface via
      glycosylphosphatidylinositol (GPI) anchors. To evaluate the importance of GPI for
      parasite survival, we cloned and disrupted a trypanosomal gene, TbGPI10, involved
      in biosynthesis of GPI. TbGPI10 encodes a protein of 558 amino acids having 25%
      and 23% sequence identity to human PIG-B and Saccharomyces cerevisiae Gpi10p,
      respectively. TbGPI10 restored biosynthesis of GPI in a mouse mutant cell line
      defective in mouse Pig-b gene. TbGPI10 also rescued the inviability of GPI10
      disrupted S. cerevisiae, indicating that TbGPI10 is the orthologue of PIG-B/GPI10
      that is involved in the transfer of the third mannose to GPI. The bloodstream
      form of T. brucei could not lose TbGPI10; therefore, GPI synthesis is essential
      for growth of mammalian stage parasites. Procyclic form cells (insect stage
      parasites) lacking the surface coat proteins because of disruption of TbGPI10 are
      viable and grow slower than normal, provided that they are cultured in
      nonadherent flasks. In regular flasks, they adhered to the plastic surface and
      died. Infectivity to tsetse flies is partially impaired, particularly in the
      early stage. Therefore, parasitespecific inhibition of GPI biosynthesis should be
      an effective chemotherapy target against African trypanosomiasis.

PMID- 10954752
TI  - Retinoic acid (RA) and As2O3 treatment in transgenic models of acute
      promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic
      process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins.
AB  - Acute promyelocytic leukemia (APL) is associated with chromosomal translocations
      always involving the RARalpha gene, which variably fuses to one of several
      distinct loci, including PML or PLZF (X genes) in t(15;17) or t(11;17),
      respectively. APL in patients harboring t(15;17) responds well to retinoic acid
      (RA) treatment and chemotherapy, whereas t(11;17) APL responds poorly to both
      treatments, thus defining a distinct syndrome. Here, we show that RA, As(2)O(3),
      and RA + As(2)O(3) prolonged survival in either leukemic PML-RARalpha transgenic
      mice or nude mice transplanted with PML-RARalpha leukemic cells. RA + As(2)O(3)
      prolonged survival compared with treatment with either drug alone. In contrast,
      neither in PLZF-RARalpha transgenic mice nor in nude mice transplanted with PLZF
      RARalpha cells did any of the three regimens induce complete disease remission.
      Unexpectedly, therapeutic doses of RA and RA + As(2)O(3) can induce, both in vivo
      and in vitro, the degradation of either PML-RARalpha or PLZF-RARalpha proteins,
      suggesting that the maintenance of the leukemic phenotype depends on the
      continuous presence of the former, but not the latter. Our findings lead to three
      major conclusions with relevant therapeutic implications: (i) the X-RARalpha
      oncoprotein directly determines response to treatment and plays a distinct role
      in the maintenance of the malignant phenotype; (ii) As(2)O(3) and/or As(2)O(3) +
      RA combination may be beneficial for the treatment of t(15;17) APL but not for
      t(11;17) APL; and (iii) therapeutic strategies aimed solely at degrading the X
      RARalpha oncoprotein may not be effective in t(11;17) APL.

PMID- 10954753
TI  - Diagnostic ultrasound activation of contrast agent gas bodies induces capillary
      rupture in mice.
AB  - Interaction of diagnostic ultrasound with gas bodies produces a useful contrast
      effect in medical images, but the same interaction also represents a mechanism
      for bioeffects. Anesthetized hairless mice were scanned by using a 2.5-MHz
      transducer (610-ns pulses with 3.6-kHz repetition frequency and 61-Hz frame rate)
      after injection of Optison and Evans blue dye. Petechial hemorrhages (PHs) in
      intestine and abdominal muscle were counted 15 min after exposure to characterize
      capillary rupture, and Evans blue extravasation was evaluated in samples of
      muscle tissue. For 5 ml small middle dotkg(-1) contrast agent and exposure to 10
      alternating 10-s on and off periods, PH counts in muscle were approximately
      proportional to the square of peak negative pressure amplitude and were
      statistically significant above 0.64 MPa. PH counts in intestine and Evans blue
      extravasation into muscle tissue were significant above 1. 0 MPa. The PH effect
      in muscle was proportional to contrast dose and was statistically significant for
      the lowest dose of 0.05 ml small middle dotkg(-1). The effects decreased nearly
      to sham levels if the exposure was delayed 5 min. The PH effect in abdominal
      muscle was significant and statistically indistinguishable for uninterrupted 100
      s exposure, 10-s exposure, 100 scans repeated at 1 Hz, and even for a single
      scan. The results confirms a previous report of PH induction by diagnostic
      ultrasound with contrast agent in mammalian skeletal muscle [Skyba, D. M., Price,
      R. J., Linka, A. Z., Skalak, T. C. & Kaul, S. (1998) Circulation 98, 290-293].

PMID- 10954754
TI  - Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in
      activated B cell-like diffuse large cell lymphomas.
AB  - B cell diffuse large cell lymphoma (B-DLCL) is a heterogeneous group of tumors,
      based on significant variations in morphology, clinical presentation, and
      response to treatment. Gene expression profiling has revealed two distinct tumor
      subtypes of B-DLCL: germinal center B cell-like DLCL and activated B cell-like
      DLCL. In a separate study, we determined that B-DLCL can also be subdivided into
      two groups based on the presence or absence of ongoing Ig gene hypermutation.
      Here, we evaluated the correlation between these B-DLCL subtypes established by
      the two different methods. Fourteen primary B-DLCL cases were studied by gene
      expression profiling using DNA microarrays and for the presence of ongoing
      mutations in their Ig heavy chain gene. All seven cases classified as germinal
      center B cell-like DLCL by gene expression showed the presence of ongoing
      mutations in the Ig genes. Five of the seven cases classified by gene expression
      as activated B cell-like DLCL had no ongoing somatic mutations, whereas, in the
      remaining two cases, a single point mutation was observed in only 2 of 15 and 21
      examined molecular clones of variable heavy (V(H)) chain gene, respectively.
      These two cases were distantly related to the rest of the activated B cell-like
      DLCL tumors by gene expression. Our findings validate the concept that lymphoid
      malignancies are derived from cells at discrete stages of normal lymphocyte
      maturation and that the malignant cells retain the genetic program of those
      normal cells.

PMID- 10954755
TI  - Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene
      associated histone acetylation.
AB  - Histone deacetylases (HDACs) catalyze the removal of acetyl groups on the amino
      terminal lysine residues of core nucleosomal histones. This activity is
      associated generally with transcriptional repression. We have reported previously
      that inhibition of HDAC activity by hydroxamic acid-based hybrid polar compounds,
      such as suberoylanilide hydroxamic acid (SAHA), induces differentiation and/or
      apoptosis of transformed cells in vitro and inhibits tumor growth in vivo. SAHA
      is a potentially new therapeutic approach to cancer treatment and is in Phase I
      clinical trials. In several tumor cell lines examined, HDAC inhibitors alter the
      expression of less than 1% of expressed genes, including the cell cycle kinase
      inhibitor p21(WAF1). In T24 bladder carcinoma cells, SAHA induces up to a 9-fold
      increase in p21(WAF1) mRNA and protein, which is, at least in part, because of an
      increase in the rate of transcription of the gene. SAHA causes an accumulation of
      acetylated histones H3 and H4 in total cellular chromatin by 2 h, which is
      maintained through 24 h of culture. An increase in the accumulation of acetylated
      H3 and H4 was detected throughout the p21(WAF1) promoter and the structural gene
      after culture with SAHA. The level of histone acetylation did not change in
      chromatin associated with the actin and p27 genes, and their mRNA expression was
      not altered during culture of T24 cells with SAHA. Thus, the present findings
      indicate that the induction of p21(WAF1) by SAHA is regulated, at least in part,
      by the degree of acetylation of the gene-associated histones and that this
      induced increase in acetylation is gene selective.

PMID- 10954756
TI  - Nociception in cyclooxygenase isozyme-deficient mice.
AB  - Prostaglandins formed by cyclooxygenase-1 (COX-1) or COX-2 produce hyperalgesia
      in sensory nerve endings. To assess the relative roles of the two enzymes in pain
      processing, we compared responses of COX-1- or COX-2-deficient homozygous and
      heterozygous mice with wild-type controls in the hot plate and stretching tests
      for analgesia. Preliminary observational studies determined that there were no
      differences in gross parameters of behavior between the different groups.
      Surprisingly, on the hot plate (55 degrees C), the COX-1-deficient heterozygous
      groups showed less nociception, because mean reaction time was longer than that
      for controls. All other groups showed similar reaction times. In the stretching
      test, there was less nociception in COX-1-null and COX-1-deficient heterozygotes
      and also, unexpectedly, in female COX-2-deficient heterozygotes, as shown by a
      decreased number of writhes. Measurements of mRNA levels by reverse transcription
      PCR demonstrated a compensatory increase of COX-1 mRNA in spinal cords of COX-2
      null mice but no increase in COX-2 mRNA in spinal cords of COX-1-null animals.
      Thus, compensation for the absence of COX-1 may not involve increased expression
      of COX-2, whereas up-regulation of COX-1 in the spinal cord may compensate for
      the absence of COX-2. The longer reaction times on the hot plate of COX-1
      deficient heterozygotes are difficult to explain, because nonsteroid anti
      inflammatory drugs have no analgesic action in this test. Reduction in the number
      of writhes of the COX-1-null and COX-1-deficient heterozygotes may be due to low
      levels of COX-1 at the site of stimulation with acetic acid. Thus, prostaglandins
      made by COX-1 mainly are involved in pain transmission in the stretching test in
      both male and female mice, whereas those made by COX-2 also may play a role in
      the stretching response in female mice.

PMID- 10954757
TI  - Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase
      activity.
AB  - Cytosolic proteolysis is carried out predominantly by the proteasome. We show
      that a large oligopeptidase, tripeptidylpeptidase II (TPPII), can compensate for
      compromised proteasome activity. Overexpression of TPPII is sufficient to prevent
      accumulation of polyubiquitinated proteins and allows survival of EL-4 cells at
      otherwise lethal concentrations of the covalent proteasome inhibitor NLVS (NIP
      leu-leu-leu-vinylsulfone). Elevated TPPII activity also partially restores
      peptide loading of MHC molecules. Purified proteasomes from adapted cells lack
      the chymotryptic-like activity, but still degrade longer peptide substrates via
      residual activity of their Z subunits. However, growth of adapted cells depends
      on induction of other proteolytic activities. Therefore, cytosolic
      oligopeptidases such as TPPII normalize rates of intracellular protein breakdown
      required for normal cellular function and viability.

PMID- 10954758
TI  - Simian virus 40 and the human mesothelium.

PMID- 10954759
TI  - Effects of estrogen replacement on the progression of coronary-artery
      atherosclerosis.
AB  - BACKGROUND: Heart disease is a major cause of illness and death in women. To
      understand better the role of estrogen in the treatment and prevention of heart
      disease, more information is needed about its effects on coronary atherosclerosis
      and the extent to which concomitant progestin therapy may modify these effects.
      METHODS: We randomly assigned a total of 309 women with angiographically verified
      coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of
      conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or
      placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line
      and follow-up coronary angiograms were analyzed by quantitative coronary
      angiography. RESULTS: Estrogen and estrogen plus medroxyprogesterone acetate
      produced significant reductions in low-density lipoprotein cholesterol levels
      (9.4 percent and 16.5 percent, respectively) and significant increases in high
      density lipoprotein cholesterol levels (18.8 percent and 14.2 percent,
      respectively); however, neither treatment altered the progression of coronary
      atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE)
      minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02
      mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus
      medroxyprogesterone acetate, and placebo, respectively. The differences between
      the values for the two active-treatment groups and the value for the placebo
      group were not significant. Analyses of several secondary angiographic outcomes
      and subgroups of women produced similar results. The rates of clinical
      cardiovascular events were also similar among the treatment groups. CONCLUSIONS:
      Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the
      progression of coronary atherosclerosis in women with established disease. These
      results suggest that such women should not use estrogen replacement with an
      expectation of cardiovascular benefit.

PMID- 10954760
TI  - Trends in the incidence of coronary heart disease and changes in diet and
      lifestyle in women.
AB  - BACKGROUND: Previous studies have found concurrent declines in blood pressure,
      serum cholesterol levels, and the incidence of and mortality from coronary
      disease. However, the effects of changes in diet and lifestyle on trends in
      coronary disease are largely unknown. METHODS: We followed 85,941 women who were
      34 to 59 years old and had no previously diagnosed cardiovascular disease or
      cancer from 1980 to 1994 in the Nurses' Health Study. Diet and lifestyle
      variables were assessed at base line and updated during follow-up. RESULTS: After
      adjustment for the effect of age, the incidence of coronary disease declined by
      31 percent from the two-year period 1980-1982 to the two-year period 1992-1994.
      From 1980 to 1992, the proportion of participants currently smoking declined by
      41 percent, the proportion of postmenopausal women using hormone therapy
      increased by 175 percent, and the prevalence of overweight, defined as a body
      mass index (the weight in kilograms divided by the square of the height in
      meters) of 25 or more, increased by 38 percent. During the study period, diet
      improved substantially. Statistically, changes in these variables--when
      considered simultaneously--explained a 21 percent decline in the incidence of
      coronary disease, representing 68 percent of the overall decline from 1980-1982
      to 1992-1994. Taken individually, the reduction in smoking explained a 13 percent
      decline in the incidence of coronary disease; improvement in diet explained a 16
      percent decline; and increase in postmenopausal hormone use explained a 9 percent
      decline. On the other hand, the increase in body-mass index explained an 8
      percent increase in the incidence of coronary disease. CONCLUSIONS: Reduction in
      smoking, improvement in diet, and an increase in postmenopausal hormone use
      accounted for much of the decline in the incidence of coronary disease in this
      group of women. An increasing prevalence of obesity, however, appears to have
      slowed the decline in the incidence of coronary disease.

PMID- 10954761
TI  - Siblings, day-care attendance, and the risk of asthma and wheezing during
      childhood.
AB  - BACKGROUND: Young children with older siblings and those who attend day care are
      at increased risk for infections, which in turn may protect against the
      development of allergic diseases, including asthma. However, the results of
      studies examining the relation between exposure to other children and the
      subsequent development of asthma have been conflicting. METHODS: In a study
      involving 1035 children followed since birth as part of the Tucson Children's
      Respiratory Study, we determined the incidence of asthma (defined as at least one
      episode of asthma diagnosed by a physician when the child was 6 to 13 years old)
      and the prevalence of frequent wheezing (more than three wheezing episodes during
      the preceding year) in relation to the number of siblings at home and in relation
      to attendance at day care during infancy. RESULTS: The presence of one or more
      older siblings at home protected against the development of asthma (adjusted
      relative risk for each additional older sibling, 0.8; 95 percent confidence
      interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six
      months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2
      to 1.0; P=0.04). Children with more exposure to other children at home or at day
      care were more likely to have frequent wheezing at the age of 2 years than
      children with little or no exposure (adjusted relative risk, 1.4; 95 percent
      confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent
      wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence
      interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3;
      95 percent confidence interval, 0.2 to 0.5; P<0.001). CONCLUSIONS: Exposure of
      young children to older children at home or to other children at day care
      protects against the development of asthma and frequent wheezing later in
      childhood.

PMID- 10954762
TI  - Genetic and clinical features of hemoglobin H disease in Chinese patients.
AB  - BACKGROUND: Normally, one pair of each of the two alpha-globin genes, alpha1 and
      alpha2, resides on each copy of chromosome 16. In hemoglobin H disease, three of
      these four alpha-globin genes are affected by a deletion, a mutation, or both. We
      studied the alpha1-globin gene abnormalities and the clinical and hematologic
      features of Chinese patients with hemoglobin H disease in Hong Kong. METHODS: We
      assessed the clinical features, hematologic values, serum ferritin levels, and
      liver function of 114 patients with hemoglobin H disease. We also performed
      echocardiography and magnetic resonance imaging of the liver and examined the two
      pairs of alpha-globin genes. RESULTS: Hemoglobin H disease in 87 of the 114
      patients (76 percent) was due to the deletion of three of the four alpha-globin
      genes (--/-alpha), a combination termed the deletional type of hemoglobin H. The
      remaining 27 patients (24 percent) had the nondeletional type of hemoglobin H
      disease, in which two alpha-globin genes are deleted and a third is mutated (-
      /alphaalphaT). All 87 patients with the deletional type of hemoglobin H were
      double heterozygotes in whom there was a deletion of both alpha-globin genes from
      one chromosome, plus a deletion of the alpha1 or alpha2 gene from the other
      chromosome (--/alpha- or --/-alpha). A variety of mutated alpha-globin genes was
      found in the patients with nondeletional type of hemoglobin H disease. Patients
      with the nondeletional type of the H disease had more symptoms at a younger age,
      more severe hemolytic anemia, and larger spleens and were more likely to require
      transfusions than patients with deletional hemoglobin H disease. The severity of
      iron overload was not related to the genotype. CONCLUSIONS: Chinese patients in
      Hong Kong with the nondeletional type of hemoglobin H disease have more severe
      disease than those with the deletional type of the disease. Iron overload is a
      major cause of disability in both forms of the disease.

PMID- 10954763
TI  - Treatment of type II gastric carcinoid tumors with somatostatin analogues.

PMID- 10954764
TI  - Images in clinical medicine. Pseudomembranous colitis.

PMID- 10954765
TI  - Blurred vision.

PMID- 10954766
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 26-2000. A 47-year-old man with recurrent pancreatitis and a
      cystic pancreatic mass.

PMID- 10954768
TI  - Correction: Congenital Autoimmune Diabetes Mellitus.

PMID- 10954767
TI  - Coronary heart disease in women--an ounce of prevention.

PMID- 10954769
TI  - Correction: The Acute Chest Syndrome of Sickle Cell Disease.

PMID- 10954770
TI  - What recourse? Liability for managed-care decisions and the Employee Retirement
      Income Security Act.

PMID- 10954771
TI  - Do estrogens effectively prevent osteoporosis-related fractures? The Group for
      the Respect of Ethics and Excellence in Science.

PMID- 10954772
TI  - Bone mineral density differences at the femoral neck and Ward's triangle: a
      comparison study on the reference data between Chinese and Caucasian women.
AB  - The incidence of hip fracture is lower in Chinese women compared with those from
      western countries, though they usually have lower bone mineral density (BMD). In
      this study, reference data (from Caucasian women) supplied by the manufacturer of
      Hologic Inc. was compared with data obtained from healthy women in Changsha,
      Hunan province, P.R.C. A total of 1488 Chinese women aged 15-95 years were
      randomly chosen for the study. Measurements of BMD were taken at the hip by dual
      energy X-ray absorptiometry (DXA) (QDR 4500A, Hologic Inc., USA). The BMD and the
      BMD decrease rate were somewhat lower than reference curves at all age groups and
      all sites except for the femoral neck and Ward's triangle. Chinese women reached
      their peak BMD 5-10 years later than their counterparts, and had a lower BMD
      decrease rate for about 35 years after peak BMD was attained. The fact that
      Chinese women take longer time to reach peak BMD and have a lower BMD decrease
      rate at the neck and Ward's triangle after peak BMD is attained protects them
      against hip fractures, and is a phenomenon that needs to be studied in the
      future.

PMID- 10954773
TI  - Bone mass in female cross-country skiers: relationship between muscle strength
      and different BMD sites.
AB  - In this cross-sectional study, bone mass and muscle strength of the thigh were
      investigated in 16 Caucasian female cross-country skiers, age 16.2 +/- 0.3 years,
      that had been ski-training for 6.4 +/- 1.8 years (range 3-9 years) and were now
      training for 6.3 +/- 2.4 hours/week (range 3-12 hours). They were compared with
      16 nonactive females, age 16.4 +/- 0.7 years. The groups were matched according
      to age, weight, height, and pubertal status. Areal bone mineral density (BMD) was
      measured using dual energy X-ray absorptiometry, in the total body, head, both
      total humerus and humerus diaphyses, spine, and in the right femoral neck,
      greater trochanter, femoral diaphysis, distal femur, proximal tibia, and tibia
      diaphysis. Bone mineral apparent density (BMAD) was also calculated for the
      femoral neck and humerus diaphyses. Isokinetic muscle strength of the quadricep
      and hamstring muscles was measured in an isokinetic dynamometer. Compared with
      the controls, the cross-country skiing group had significantly higher BMD in the
      right whole humerus (6.9%), left whole humerus (9.2%), left humerus diaphysis
      (8.1%), femoral neck (8.9%), greater trochanter (9.3%), femur diaphysis (7.6%),
      and BMAD of the femoral neck (+19.4%). In the nonactive group there were
      significant side-to-side differences in BMD of the whole humeri, humerus
      diaphyses, and BMAD of the humerus diaphyses (3.1%, 5.4%, and 8.8% higher in the
      right arm, respectively). No such differences were found in the cross-country
      skiing group. Lean body mass was significantly higher in the cross-country skiers
      (21.7%), and fat mass (-25.5%) and body fat percent (-28.0%) were significantly
      lower compared with the nonactive group. There were, however, no significant
      differences in concentric peak torque of the thigh muscles between the two
      groups. Stepwise regression analyses revealed that BMI was the best predictor of
      several sites in the nonactive group. In the cross-country group, on the other
      hand, muscle strength was a strong predictor of BMD, both at adjacent and more
      distant BMD sites. In conclusion, it seems that this type of endurance training
      is associated with a site-specific higher bone mass that may be associated with
      the type and magnitude of loading during off-season and during the main sports
      activity, cross-country skiing.

PMID- 10954774
TI  - Effect of high impact activity on bone mass and size in adolescent females: A
      comparative study between two different types of sports.
AB  - The purpose of this cross-sectional study was to investigate the influence of two
      different types of weight-bearing activity, muscle strength, and body composition
      on bone mineral density (BMD), bone mineral content (BMC), and bone area in three
      different groups of late adolescent girls. The first group consisted of 10
      females participating in competitive rope-skipping (age 17.8 +/- 0.8 years)
      training for 6.7 +/- 3.1 hours/week; the second group consisted of 15 soccer
      players (age 17.4 +/- 0.8 years) training for 6.1 +/- 2.0 hours/week; and the
      third group consisted of 25 controls (age 17.6 +/- 0.8 years) with physical
      activity of 0.9 +/- 1.1 hours/week. The groups were matched for age, height, and
      weight. BMD (g/cm(2)), BMC (g), and bone area (cm(2)) of the total body, lumbar
      spine, hip, total femur, distal femur, diaphyses of femur and tibia, proximal
      tibia, and humerus were measured using dual-energy X-ray absorptiometry (DXA).
      Bone density was also assessed in the radial forearm site of the dominant limb in
      the rope skippers and in 10 matched controls. The rope skippers had 22% higher
      BMD at the ultradistal site (P < 0.01). Both high-activity groups had
      significantly higher BMD (P < 0.05) at most loaded sites compared with the
      control group. When adjusting for differences in lean mass and starting age of
      sport-specific training between the activity groups, the rope-skipping group had
      a higher BMD of the total body, lumbar spine, and right humerus compared with the
      soccer group. They also had a significantly higher bone area of the total body,
      total femur, and the proximal femur than both other groups, and a significantly
      higher bone area of the tibia diaphysis, compared with the soccer group. In a
      multivariate analysis among all subjects (n = 50), all BMD sites, except the
      femur diaphysis, distal femur, and proximal tibia, were significantly related to
      type of physical activity (beta = 0.25-0.43, P < 0.05). The bone area values at
      different sites were strongly related to muscle strength and parameters related
      to body size [height, weight, lean mass, fat mass, and body mass index (BMI)]. In
      conclusion, it appears that in late adolescent women, weight-bearing activities
      are an important determinant for bone density, and high impact activities such as
      jumping also seem to be associated with a modification of the bone geometry
      (hence, the bone width) at the loaded sites.

PMID- 10954775
TI  - Exercise-trained young men have higher calcium absorption rates and plasma
      calcitriol levels compared with age-matched sedentary controls.
AB  - The effect of physical activity on human calcium (Ca) metabolism is still not
      completely understood. Thus, we investigated fractional Ca absorption using a
      stable strontium test (Fc(240)), calciotropic hormones, and renal Ca excretion in
      31 young men with a high activity level (GH) and in 26 age-matched sedentary
      control subjects (GL). Weekly hours spent on physical activity, obtained with a
      questionnaire were 15.0 +/- 6.6 (GH) and 1.0 +/- 1.4 (GL), respectively. Serum
      testosterone levels were significantly lower in GH compared with GL (P < 0.005).
      Dietary Ca intake (4-day food record) was twice as high in GH compared with GL
      men (P < 0.001). GH had significantly higher serum calcitriol levels and Fc(240)
      values than GL (P < 0.001 and P < 0.01, respectively). In a stepwise multiple
      regression analysis including serum levels of 25-hydroxyvitamin D, calcitriol,
      testosterone, and dietary Ca intake, only calcitriol was significantly correlated
      with Fc(240) (P = 0. 017). Twenty-four hour renal Ca excretion was only slightly
      higher in GH compared with GL (P < 0.05). However, additional Ca losses might
      have occurred through the extensive sweating of GH, as indicated by a difference
      of 1.7 liter between fluid intake and renal fluid excretion (P < 0.001). In
      summary, we observed a higher fractional Ca absorption rate in physically active
      young men compared with sedentary controls which is probably mediated by
      calcitriol. The low testosterone serum levels of the athletes were obviously not
      a limiting factor in Ca absorption efficiency. An additional Ca retention might,
      however, only be obtained if absorbed Ca exceeded total obligatory Ca losses.

PMID- 10954776
TI  - Peripheral bone mass is not affected by winter vitamin D deficiency in children
      and young adults from Ushuaia.
AB  - Low vitamin D levels in elderly people are associated with reduced bone mass,
      secondary hyperparathyroidism, and increased fracture risk. Its effect on the
      growing skeleton is not well known. The aim of this study was to evaluate the
      possible influence of chronic winter vitamin D deficiency and higher winter
      parathyroid hormone (PTH) levels on bone mass in prepubertal children and young
      adults. The study was carried out in male and female Caucasian subjects. A total
      of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young
      adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were
      recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude),
      where the population is known to have low winter 25OHD levels and higher levels
      of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where
      ultraviolet (UV) radiation and vitamin D nutritional status in the population are
      adequate all year round. Bone mineral content (BMC) and bone mineral density
      (BMD) of the ultradistal and distal radius were measured in the young adults.
      Only distal radius measurements were taken in the children. Similar results were
      obtained in age-sex matched groups from both areas. The only results showing
      significant difference corresponded to comparison among the Ushuaian women: those
      whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values
      than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/-
      0.041 g/cm(2), P < 0.02; 3.131 +/- 0.367 versus 3.339 +/- 0.386 g, P < 0.05,
      respectively). In conclusion, peripheral BMD and BMC were similar in children and
      young adults from Ushuaia and Buenos Aires in spite of the previously documented
      difference between both areas regarding UV radiation and winter vitamin D status.
      BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and
      vitamin D deficiency on the growing skeleton should be studied further.

PMID- 10954777
TI  - Ipriflavone, a synthetic phytoestrogen, enhances intestinal calcium transport in
      vitro.
AB  - Ipriflavone (IP), a synthetic isoflavone, prevents bone loss associated with
      ovarian hormone deficiency in women and animal models. This protective effect of
      IP may be partly due to its ability to enhance calcium absorption. The purpose of
      this study was to examine the effects of IP and 17beta-estradiol (E(2)) on in
      vitro intestinal calcium transport in an ovariectomized rat model using E(2) as a
      positive control. Forty-eight 90-day-old female Sprague-Dawley rats were divided
      into four groups: one sham-operated (sham) and three ovariectomized groups. The
      ovx groups were either control (ovx), supplemented with IP (100 mg/kg body weight
      daily) via gavaging (ovx+IP), or injected with E(2) (10 microg/kg body weight)
      (ovx+E(2)). Animals were fed diets containing 0.4% calcium, 0.3% phosphorus, and
      0.195 nmol vitamin D(3)/g for 35 days from the date of surgery. Animals were
      exsanguinated, and isolated cells from the duodenum, jejunum, ileum, and colon
      were used to measure in vitro calcium uptake. Calcium uptake by duodenal cells
      was significantly greater in the IP and E(2)-treated animals compared with the
      ovx control group. In addition, calcium uptake by the ileal and colonic cells of
      the E(2)-treated animals was significantly greater compared with all the other
      groups. The results confirm our earlier findings implicating a role for estrogen
      in duodenal calcium uptake. The findings also indicate that IP, although less
      potent than estrogen, significantly enhances calcium uptake in the duodenum, the
      active site of calcium absorption.

PMID- 10954778
TI  - Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in
      normal and osteoarthritic cartilage and bone.
AB  - Osteocalcin (OC), which is a marker of the mature osteoblasts, can also be found
      in posthypertrophic chondrocytes of the epiphyseal growth plate, but not in
      chondrocytes of the resting zone or in adult cartilage. In human osteoarthritis
      (OA), chondrocytes can differentiate to a hypertrophic phenotype characterized by
      type X collagen. The protein- and mRNA-expression pattern of OC was
      systematically analyzed in decalcified cartilage and bone sections and
      nondecalcified cartilage sections of human osteoarthritic knee joints with
      different stages of OA to investigate the differentiation of chondrocytes in OA.
      In severe OA, we found an enhanced expression of the OC mRNA in the subchondral
      bone plate, demonstrating an increased osteoblast activity. Interestingly, the OC
      protein and OC mRNA were also detected in osteoarthritic chondrocytes, whereas in
      chondrocytes of normal adult cartilage, both the protein staining and the
      specific mRNA signal were negative. The OC mRNA signal increased with the
      severity of OA and chondrocytes from the deep cartilage layer, and proliferating
      chondrocytes from clusters showed the strongest signal for OC mRNA. In this late
      stage of OA, chondrocytes also stained for alkaline phosphatase and type X
      collagen. Our results clearly show that the expression of OC in chondrocytes
      correlates with chondrocyte hypertrophy in OA. Although the factors including
      this phenotypic shift in OA are still unknown, it can be assumed that the altered
      microenvironment around osteoarthritic chondrocytes and systemic mediators could
      be potential inducers of this differentiation.

PMID- 10954779
TI  - Parathyroid hormone modulates the response of osteoblast-like cells to mechanical
      stimulation.
AB  - Mechanical loading stimulates many responses in bone and osteoblasts associated
      with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar
      signaling pathways in osteoblasts, we postulate that PTH can potentiate the
      effects of mechanical stimulation. Using an in vitro four-point bending device,
      we found that expression of COX-2, the inducible isoform of cyclooxygenase, was
      dependent on fluid forces generated across the culture plate, but not physiologic
      levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during
      loading increased COX-2 expression at both subthreshold and threshold levels of
      fluid forces compared with either stimuli alone. We also demonstrated that
      application of fluid shear to MC3T3-E1 cells induced a rapid increase in
      [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow
      and PTH did produce a significantly greater [Ca(2+)](i) response and increased
      the number of responding cells than is found in fluid shear alone. The
      [Ca(2+)](i) response to these stimuli was significantly decreased when the
      mechanosensitive channel inhibitor, gadolinium, was present. These studies
      indicate that PTH increases the cellular responses of osteoblasts to mechanical
      loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i)
      by modulating the mechanosensitive channel.

PMID- 10954781
TI  - Development and application of a synthetic peptide-based osteocalcin assay for
      the measurement of bone formation in mouse serum.
AB  - The mouse is frequently used as an animal model to study skeletal mechanisms
      relevant to humans. Biochemical markers of bone formation and resorption provide
      one of the key parameters for assessing skeletal metabolism. One biochemical
      marker that has proven to be useful in the studies of mouse skeletal metabolism
      is osteocalcin. Assay for osteocalcin is available in the mouse. The present
      study describes development of an osteocalcin radioimmunoassay (RIA) using a
      synthetic peptide. Intact osteocalcin purified from mouse bone extracts shows
      parallel displacement with synthetic peptide. Sensitivity of the RIA was 19
      ng/ml. The average (n = 9) intra- and interassay coefficient of variation for two
      controls was less than 10%; the averaged recoveries were 106%. The osteocalcin
      concentration measured by peptide RIA shows a high correlation (r = 0.88, n =
      117, P < 0.0001) with an intact osteocalcin assay. In addition, when the intact
      assay and peptide assays were applied to evaluate skeletal perturbation, similar
      results were obtained. Accordingly, osteocalcin levels measured by both intact
      and peptide-based RIA in 8-week C57BL/6J (n = 8) mice treated with PTH 1-34 were
      twofold higher compared with the vehicle-treated control group. Further studies
      of the application of the peptide-based RIA for osteocalcin revealed that
      osteocalcin levels in 4-week postovariectomized (OVX) C57BL/6N mice (n = 10) were
      80% higher than the sham-operated (n = 10) mice receiving vehicle. OVX mice
      receiving weekly injections of estradiol (400 microg/kg body weight) were 38%
      lower compared with the OVX group treated with vehicle. In conclusion, the
      peptide-based RIA has analytical and a discriminative power similar to that of
      the intact osteocalcin assay but has the advantage that the resources for this
      assay are much easier to accrue.

PMID- 10954780
TI  - Calcitonin increases the concentration of insulin-like growth factors in serum
      free cultures of human osteoblast-line cells.
AB  - The current studies were intended to determine whether the anabolic effects of
      calcitonin (CT) on human osteoblast-line cells were (1) unique to osteosarcoma
      cells or also evident in osteoblast-line cells derived from normal human bone;
      and/or (2) associated with effects on several insulin-like growth factor (IGF)
      system components. Preliminary studies identified several osteoblastic cell
      lines, derived from normal human bone, which showed calcitonindependent increases
      in cell proliferation, alkaline phosphatase activity, and/or (45)Ca uptake (P <
      0.05-P < 0.001). Two of these cell lines-(human vertebrae) HBV-155 and HBV-163
      were included with the human osteosarcoma cell line, SaOS-2, in most of our
      subsequent studies of calcitonin effects on selected IGF system components: IGF
      II, IGF-I, and IGF binding proteins -3, -4, and -5. The results of those studies
      revealed that a 48 hour exposure to salmon CT caused a dose-dependent (0.03-3
      mU/ml) increase in the net extracellular level of IGF-II (r = 0.96, P < 0.01) in
      serum-free cultures of SaOS-2 cells, with a maximal 60% increase at the highest
      tested dose (P < 0.02). Similar effects were seen with HBV-163 cells (r = 0.90, P
      < 0.01) and HBV-155 cells (r = 0.55, P < 0.02). The effect of calcitonin on the
      extracellular level of IGF-II was biphasic with respect to time: it decreased at
      6 hours (P < 0.005 and P < 0.001, for SaOS-2 cells and HBV-163 cells,
      respectively) and increased at 24 hours (P < 0.02 and P < 0.05). These calcitonin
      dependent increases in the extracellular level of IGF-II were associated with
      parallel increases in IGF-I (P < 0.005 for SaOS-2 cells and P < 0.03 for HBV-163
      cells), but calcitonin did not affect the extracellular level of transforming
      growth factor (TGF)-beta. The calcitonin-dependent changes in IGF-II were not
      associated with changes in the extracellular levels of IGF binding proteins -3, 
      4, or -5. Finally, our studies showed that two other members of the CT
      superfamily-CT gene-related peptide and amylin-did not mimic the effect of CT to
      increase the extracellular level of IGF-II. Together, these data demonstrate that
      human osteoblast-line cells derived from normal human bone can respond to CT, and
      that those responses can include CT dose- and time-dependent increases in the
      extracellular levels of IGF-I and IGF-II.</hea

PMID- 10954782
TI  - Fractographic examination of racing greyhound central (navicular) tarsal bone
      failure surfaces using scanning electron microscopy.
AB  - The greyhound is a fatigue fracture model of a short distance running athlete.
      Greyhounds have a high incidence of central (navicular) tarsal bone (CTB)
      fractures, which are not associated with overt trauma. We wished to determine
      whether these fractures occur because of accumulation of fatigue microdamage. We
      hypothesized that bone from racing dogs would show site-specific microdamage
      accumulation, causing predisposition to structural failure. We performed a
      fractographic examination of failure surfaces from fractured bones using scanning
      electron microscopy and assessed microcracking observed at the failure surface
      using a visual analog scale. Branching arrays of microcracks were seen in failure
      surfaces of CTB and adjacent tarsal bones, suggestive of compressive fatigue
      failure. Branching arrays of microcracks were particularly prevalent in remodeled
      trabecular bone that had become compact. CTB fractures showed increased
      microdamage when compared with other in vivo fractures (adjacent tarsal bone and
      long bone fractures), and ex vivo tarsal fractures induced by monotonic loading
      (P < 0.02). It was concluded that greyhound racing and training often results in
      CTB structural failure, because of accumulation and coalescence of branching
      arrays of fatigue microcracks, the formation of which appears to be predisposed
      to adapted bone.

PMID- 10954784
TI  - Association between QUS and structural parameters?

PMID- 10954785
TI  - European calcified tissue society

PMID- 10954783
TI  - Measurement of bone density around total knee arthroplasty using fan-beam dual
      energy X-ray absorptiometry.
AB  - The clinical survival of joint arthroplasties is clearly associated with the
      quality of surrounding bone environment. Bone mineral density (BMD) is an
      important measure of bone strength and quality. Periprosthetic BMD can be
      measured by using dual-energy X-ray absorptiometry (DXA) with special software
      algorithms. We studied short-term reproducibility of the periprosthetic BMD
      measurements after total knee arthroplasty (TKA) in 30 patients with primary
      osteoarthrosis. The operated knees and the contralateral control knees were
      measured twice and the results were expressed as a coefficient of variation
      (CV%). The average precision error was 3.1% in femoral regions of interest (ROI)
      and 2.9% in tibial ROIs after TKA. In the prosthesis-free control knees, CV% were
      similar; 3.2% and 2.5%, respectively. The best precision was found in the femoral
      diaphyses above the implant (1.3%), whereas the least reproducible BMD was
      determined in the patellar region of the TKA knees (6.9%). Our results confirm
      that DXA measures precisely small bone mineral changes around TKA and makes it
      possible to follow bone remodeling DXA and may provide a feasible method for
      monitoring TKA in the future.

PMID- 10954786
TI  - Aesthetic refinements in nose reconstruction.
AB  - Reconstruction of the nose must be performed whenever a loss of tissue occurs in
      the nasal pyramid. Partial and subtotal losses are more frequently encountered
      and may concern the external covering, the supporting structures, the lining, as
      well as the possible combination of these layers. Correct examination of the
      patient, helped by photographs, X-rays, and other aids, is invaluable to the
      diagnosis. These diagnostic resources are also helpful for planning the surgery.

PMID- 10954788
TI  - Systematic procedure for ultrasonically assisted lipoplasty.
AB  - It is well known that liposuction is the extraction of fat tissue from localized
      areas through small incisions with the use of a cannula and a vacuum pump. Since
      we began liposuction 18 years ago in our Department of Plastic and Reconstructive
      Surgery at the Clinica RUBER of Madrid, more than 1,300 patients have been
      treated with this procedure. During this time, instruments and techniques have
      been dramatically improved: there have been changes in methods (from the dry
      method to the wet and super-wet ones), in instruments (from the large caliber
      cannulae to the small caliber ones), and in application (from the deep aspiration
      plane to the superficial one) [1-5]. We presently have completely developed a
      systematic procedure for conventional liposuction (CL) which produces excellent
      results and provides a foreseen evolution in all patients, and that we have
      combined with the new ultrasonically assisted lipoplasty (UAL) to get very
      satisfactory results.

PMID- 10954787
TI  - External ultrasound used in conjunction with superficial subdermal liposuction: a
      safe and effective technique.
AB  - The authors present their experience with the external ultrasound (EU) used in
      conjunction with superficial subdermal liposuction (SSL) to achieve better
      results in a safe, predictable, and reproducible way, and discuss the safety of
      liposuction and the related methods of anesthesiology.

PMID- 10954789
TI  - External ultrasound-assisted lipoplasty from our own experience.
AB  - External ultrasound-assisted liposuction (XUAL) is a new technique that requires
      traditional aspirative liposuction after the application of high frequency
      ultrasonic fields delivered through the skin into a wetted tissue. Initial data
      suggest that it has some advantages over the traditional procedure, especially
      regarding the achievement of less traumatic surgery with superior clinical
      outcome. This preliminary report describes a comparative study between
      conventional liposuction and the external ultrasound-assisted technique as the
      modality of treatment for fat deposits in 65 bilateral anatomical areas. The
      results showed considerable superiority of the ultrasound-assisted series. We
      found less resistance to the canulla with more rapid removal of fat and the
      aspirated tissue showed less blood content with intact viable fat cells. Patients
      report less pain and discomfort on the ultrasound-treated sides and we found less
      swelling and bruising, with superior skin shrinkage. Clinical recovery was also
      enhanced by the external ultrasound and no complications were reported with the
      technique.

PMID- 10954790
TI  - Very superficial ultrasound-assisted lipoplasty for the treatment of axillary
      osmidrosis.
AB  - Treatment of axillary osmidrosis has been mainly concerned with surgical excision
      of glandular tissues and involved major surgical procedures with high morbidities
      and many complications. Search for a less invasive procedure for axillary
      osmidrosis resulted in the use of liposuction. However, there have been
      controversies over the efficacy of this method. The problem was that liposuction
      could not effectively remove the apocrine gland located in the dermis and
      dermosubcutaneous junction. A high rate of residual malodor and dissatisfaction
      were reported. The author used ultrasound-assisted lipoplasty (UAL) in the very
      superficial plane to remove the apocrine gland located in the dermis and
      dermosubcutaneous junction. The purpose of this study was to prove the efficacy
      of the very superficial UAL (VSUAL) for the treatment of axillary osmidrosis.
      From December 1998 to December 1999, 21 consecutive patients underwent UAL in
      their axilla for axillary osmidrosis. The follow-up period ranged from 2 to 12
      months (mean: 8 months). UAL was performed in the very superficial plane with an
      amplitude of 40%. The very superficial UAL (VSUAL) was done mainly in a
      withdrawing manner with the tip of the cannula against the skin. The UAL (VSUAL)
      was done aggressively until the skin changed slightly erythematous. The results
      were assessed subjectively and objectively, and classified as excellent, good,
      fair, and poor. Nineteen patients were graded as excellent and one patient as
      good. The total satisfaction rate was 95.2%. One patient complained of residual
      malodor in her left axilla. There were no cases of skin necrosis, hematoma, or
      seroma. Histology showed partial removal of the subcutaneous layer and deep
      dermis, and degenerative epithelial changes in the apocrine glands in the
      residual deep dermis. These microscopic findings meant near-total functional
      ablation of the apocrine gland in the axilla comparable to "flap-to-graft
      conversion" or surgical excision of axillary skin. The UAL (VSUAL) for axillary
      osmidrosis has the advantages of a high success rate with minimal complications.
      Rapid recovery, less restriction of movement, and tiny scars were other major
      benefits of this technique. Therefore, UAL (VSUAL) is a viable option for
      treatment of axillary osmidrosis.

PMID- 10954791
TI  - Treatment of axillary and palmar hyperhidrosis with botulinum toxin.
AB  - The author presents his experience with hyperhidrosis treatment using type-A
      botulinum toxin. The drug was applied on axillary, palmar, plantar, facial,
      inguinal, and gluteus areas for a 36-month period. The effect achieved-sweating
      decrease-was observed in 100% of the patients for a variable period ranging from
      5 to 14 months. There was a slight decrease in hand muscle strength in some
      cases, which was spontaneously recovered after 2 weeks.

PMID- 10954793
TI  - Intradermal stitch blepharoplasty for orientals: does It disappear?
AB  - Intradermal stitch blepharoplasty is one of the most frequently performed
      aesthetic surgeries in Japan. The major disadvantage of this method is the
      general feeling that it is nonpermanent. Mutou and Mutou [1] first published this
      technique in 1972. From 1957 to 1997, they have performed 20,098 cases of this
      procedure. The aim of this study was to furnish a retrospective analysis of a
      failure rate after intradermal double-eyelid operations that had been performed
      by a single surgeon (Y. Mutou). We evaluated consecutive patients (male 115,
      female 1,457) from 1986 to 1993 who underwent intradermal blepharoplasty at
      Sapporo Chuo Keisei Geka Clinic. Fifty patients (male 3, female 47) revisited our
      clinic complaining of the "disappearance" or loss of the fold. The estimated
      disappearing rate was 3.43%. Thirty percent of the disappearance occurred within
      1 year. Eighty-eight percent of the disappearances occurred within 5 years
      postoperatively.

PMID- 10954792
TI  - Cross-cultural understanding of aesthetic surgery: the male cosmetic surgery
      patient in japan and the USA.
AB  - This review describes the historical development of aesthetic surgery in Japan
      and parallels with the development of the specialty in the United States. The
      focus is on the consequences of aesthetic surgery in the male patient when
      collaboration between mental health clinicians and surgeons lags. The cultural,
      social, and psychological issues raised are relevant to the diverse cultural
      groups now seeking aesthetic surgery in the United States. Case illustrations are
      a reminder to aesthetic surgeons of the potential need for more comprehensive
      evaluation in the group of male patients who may be at added risk for negative
      outcomes in terms of satisfaction.

PMID- 10954794
TI  - Endoscopic deep periorbital lifting: study and results based on 50 consecutive
      cases.
AB  - The endoscopic deep periorbital lifting is a surgical technique for rejuvenation
      of the upper two-thirds of the face. The operative principle is the suspension of
      the premalar tissues to the superficial temporal aponeurosis. This operation
      decreases the height of the inferior eyelid, corrects the nasolabial fold, and
      enhances the relief of the cheekbone. We have studied 50 consecutive cases
      operated on between 1995 and 1999; 70% had good to excellent results. The
      cutaneous palpebral resection must be inferior or equal to 5 mm to avoid the risk
      of a postoperative round eye. The subperiosteal undermining of premalar tissue
      gives the best results and lowers the risk of transitory facial paresis.

PMID- 10954795
TI  - Prophylactic antibiotics in aesthetic and reconstructive surgery.
AB  - The widespread use of antibacterial agents for prophylaxis has altered surgical
      practice markedly in the past 20 years and now represents one of the most
      frequent uses of antibiotics in hospitals, accounting for as many as half of all
      antibiotics prescribed. The present study was undertaken to determine the
      patterns of and reasons for antibacterial agent usage by today's practicing
      plastic surgeons in Israel. A survey of 78 Israeli plastic surgeons certified by
      the Israeli Association of Plastic Surgery was conducted. Questionnaires were
      mailed to all the certified plastic surgeons; 66 (84.6%) were completed and
      returned. The results indicate that prophylactic antibiotics are administered in
      a high percentage of aesthetic and reconstructive surgeries except for those in
      eyelids and nose. Most of the surgeons prefer to prescribe cephalosporins as
      their antibiotics of choice and the timing of administration is before or at the
      beginning of surgery. Placement of drains did not change the decision to use
      prophylaxis. Diabetes mellitus, steroid treatment, and chronic lung disease have
      a direct influence on the decision to use antibiotics; however, conditions such
      as ischemic heart disease, hypertension, and cigarette smoking do not influence
      their use. Personal experience was the main reason for prescribing antimicrobial
      agents. We conclude that although the infection rate in aesthetic and
      reconstructive operations is extremely low, most Israeli plastic surgeons still
      prefer to administer prophylactic antibiotics though no scientific hard data is
      available.

PMID- 10954796
TI  - Aesthetic analysis of the ideal female leg.
AB  - The aesthetics of the attractive leg are dependent on three principle factors:
      length, circumference, and shape. Advances in surgical techniques and
      instrumentation have the ability to predict an aesthetic result in contouring the
      leg. However, because of patient variability and differing opinions of the
      surgeon, the leg aesthetics criteria and thus surgical goals have not been
      clearly defined. We performed an evaluation of Taiwan Chinese female leg
      aesthetics by using two study groups. Popular fashion models were evaluated and
      compared with our attractive female population. We noticed subjectively that
      there are similar leg shapes in both groups. Criteria that contribute to the
      aesthetics of the attractive legs can be used as guides for doctors and patients
      to achieve a more aesthetic and predictable leg contour.

PMID- 10954797
TI  - Correction of inverted nipples.

PMID- 10954798
TI  - FORUM: A Context for Participation in Sustainable Development.
AB  - / The relevant literature is abound with different definitions for
      sustainability, but the most meaningful definition is set within an evolutionary
      framework. Mechanistic and evolutionary frameworks for sustainable development
      are discussed. Evolution and adaptation are characteristics of complex adaptive
      systems, and a new understanding of sustainable development can be gleaned by
      using the complex adaptive systems framework. This approach to sustainable
      development issues implicitly requires proactive involvement by the public. This
      paper supports that bottom-up participation needs to be nurtured. Appropriate
      processes to enable participation need to be designed and implemented.

PMID- 10954799
TI  - PROFILE: Tourism Contribution to Agro-Ecosystems Conservation: The Case of Lesbos
      Island, Greece.
AB  - / The modernization of agriculture and the development of other economic sectors
      have prompted the abandonment of cultivated areas, which are marginally
      productive. Specifically, olive groves in Greece are transformed into pastures
      due to their location in inaccessible mountainous regions where breeding and
      raising of sheep and goats are the main economic activities. Overgrazing degrades
      the environment, exhausts natural resources, and prevents natural regeneration.
      The Greek islands have limited possibilities of development, except for their
      coastal areas where the growth of tourism is possible.The objective of this study
      was to investigate the impact of tourism activities on olive tree cultivation and
      the human population of the island of Lesbos. The presence or absence of tourism
      is related with the maintenance or abandonment of olive tree cultivation and
      population changes for each community. A spatial segregation of the island is
      evident, related to tourist development, olive tree cultivation, and population
      change. The results of the study demonstrate that in communities where tourism
      plays an important role olive tree cultivation is preserved and the population is
      stable. The preservation of the agro-ecosystem is assured while the olive groves
      remain productive. Simultaneously, the landscape, which provides specific
      attractions for tourism, is not altered.

PMID- 10954800
TI  - Identifying Opportunities for Decision Support Systems in Support of Regional
      Resource Use Planning: An Approach Through Soft Systems Methodology.
AB  - / Regional resource use planning relies on key regional stakeholder groups using
      and having equitable access to appropriate social, economic, and environmental
      information and assessment tools. Decision support systems (DSS) can improve
      stakeholder access to such information and analysis tools. Regional resource use
      planning, however, is a complex process involving multiple issues, multiple
      assessment criteria, multiple stakeholders, and multiple values. There is a need
      for an approach to DSS development that can assist in understanding and modeling
      complex problem situations in regional resource use so that areas where DSSs
      could provide effective support can be identified, and the user requirements can
      be well established. This paper presents an approach based on the soft systems
      methodology for identifying DSS opportunities for regional resource use planning,
      taking the Central Highlands Region of Queensland, Australia, as a case study.

PMID- 10954801
TI  - Environmental Health Policy: Analytic "Framing" of the Great Lakes Picture.
AB  - / The International Joint Commission (IJC) has overseen the implementation of the
      Great Lakes Water Quality Agreement between Canada and the United States for 25
      years. Part of its mandate has been to facilitate international cooperation among
      a diversity of stakeholders focusing on the "waters" and the "ecosystem." In the
      1970s policy focused on phosphorus reduction and individual contaminants, with
      some efforts (after 1978) to take an ecosystem (ecological perspectives)
      approach. In the last 15 years human health effects from (real and perceived)
      environmental causes have received considerable recognition. By contrast, less
      concern has been expressed for what is traditionally considered "environment"
      issues (such as protecting fish species). This shift at the policy level is well
      illustrated in the manner in which human health is increasingly used as a way for
      mobilizing environmental agendas. This paper analyzes nine IJC biennial reports
      to track how the framing of Great Lakes issues has shifted from concern for its
      waters to concern for human neurobehavior and reproductive systems. Frame
      analysis is used to conceptualize the controversies that are expressed through
      the Great Lakes policy documents. The analysis of the reports also reveals a
      shift in operational frames, used by the IJC to mobilize decision-makers into
      action.

PMID- 10954802
TI  - Conserving the Biological Diversity of Forests: Program and Organizational
      Experiences of State Governments in the United States.
AB  - / Major responsibility for conserving forest biodiversity is often assigned to
      natural resource agencies. Often unknown is the appropriate administrative
      context for doing so, especially the organizational location for biodiversity
      programs in state government, suitable levels of financial and professional
      investment in biodiversity programs, processes useful for coordinating programs
      located in different administrative settings, and the effectiveness of
      biodiversity programs, especially conditions associated with programs judged to
      be very effective. Focusing on forests, a nationwide survey of 156 forestry
      agency and biodiversity program administrators in all 50 states was undertaken.
      Effective forest biodiversity programs were those with a long-range plan,
      administered as a single organizational unit, located in close organizational
      proximity to a state's forestry agency, actively providing management practice
      advice to landowners, administrators, and the public, and firm actions taken to
      ensure coordination with other natural resource programs.

PMID- 10954803
TI  - RESEARCH: Triage Law Enforcement: Societal Impacts on National Forests in the
      West.
AB  - / Uses of outdoor natural areas, like National Forests in the United States, have
      been undergoing change. Some changes, including criminal activities and domestic
      terrorism, may have quite important impacts to outdoor enthusiasts and managers.
      Activities include some relatively traditional management challenges, like arson
      and thefts, and newer challenges, such as domestic violence and murder. To better
      understand the prevalence and impacts of these activities, selected managers in
      the western United States were interviewed in summer and fall 1998. Results
      indicate criminal activities and domestic terrorism are found in both urban
      interface and rural sites. The most prevalent challenges were arson, criminal
      damage, domestic violence, dumping of household trash and landscape materials,
      marijuana cultivation, satanic cult activity, and thefts. Not as prevalent but
      found in almost all study sites were body dumping, extremist group activity, gang
      activity, murders, and suicides. Managers felt that most outdoor recreationists
      were unaffected by the activities. Most managers noted the increasing prevalence
      and the costs to management in time, personnel, and in other ways. They noted
      that their job had ceased being one of natural resources law enforcement and
      became one of "city" law enforcement. The findings of the study raise serious
      issues that require additional research.

PMID- 10954804
TI  - Invasion of Gleditsia triacanthos in Lithraea ternifolia Montane Forests of
      Central Argentina.
AB  - / The aim of this work is to study the invasion system constituted by the alien
      species Gleditsia triacanthos and the native dominant Lithraea ternifolia in
      montane forests of central Argentina, considering life history and demographic
      traits of both the alien and the native species and different site conditions for
      population growth (good and bad sites). Matrix models are applied to project the
      consequences of differences in vital rates for population growth. Analyzing these
      models helps identify which life cycle transitions contributed most to population
      growth. Obtained population growth rates are considered to assess predicted rates
      of spread using the reaction-diffusion (R-D) model. G. triacanthos presents many
      of the life history traits that confer plants high potential for invasiveness:
      fast growth, clonal and sexual reproduction, short juvenile period, high seed
      production, and high seed germinability. These traits would ensure G. triacanthos
      invasive success and the displacement of the slow-growing, relatively less fecund
      native L. ternifolia. However, since disturbance and environmental heterogeneity
      complicate the invasibility pattern of G. triacanthos in these montane forests,
      the outcome of the invasion process is not straightforward as could be if only
      life history traits were considered.Great variation in demographic parameters was
      observed between populations of each species at good and bad sites. Though both
      good and bad sites signified increasing or at least stable populations for G.
      triacanthos, for L. ternifolia bad sites represented local extinction. Analyzing
      the results of matrices models helps design the optimal management for the
      conservation of L. ternifolia populations while preventing the invasion by G.
      triacanthos. The predicted asymptotic rate of spread for G. triacanthos at the
      good site was fourfold greater than the predicted one for L. ternifolia, although
      the difference was much smaller considering the bad site. The usefulness of the R
      D model to study this invasion system is discussed.

PMID- 10954805
TI  - Test of a Model to Assess the Condition of Lodgepole Pine Stands.
AB  - / A predictive model for assessing stand condition as a function of suitability
      for achieving specified management objectives was originally developed using a
      data set for only 28 stands. In this study, we evaluate the model using an
      operational-sized data set composed of currently collected stand inventory data
      for 238 stands in the Snowy Range of the Medicine Bow National Forest in southern
      Wyoming. We compared its predictions of old growth suitability to results of a
      separate special old growth survey. Stands were characterized as profiles of
      variables derived from stand inventory data, and plotted as points in two
      dimensional space where similarity between stands was reflected by the distance
      between their points. Results suggest the model is useful for classifying stand
      condition using relatively large sets of data currently collected during routine
      stand inventories.

PMID- 10954806
TI  - The Effects of Irrigation on Revegetation of Semi-Arid Coastal Sage Scrub in
      Southern California.
AB  - / To test the appropriateness and applicability of irrigation for restoration of
      coastal sage scrub, a semi-arid vegetation type native to southern California, a
      field study comparing four irrigation schedules-no irrigation, spring irrigation
      only, summer irrigation only, and irrigation year round as needed-was
      established. A seed mixture of six native shrub species was broadcast, and the
      effect of irrigation on emergence and establishment was evaluated. Restoration of
      arid and semi-arid vegetation is challenging because of the severe environmental
      conditions inherent to these ecosystems. In particular, the low and unpredictable
      nature of precipitation can limit the chances for successful establishment of
      perennial species. Under conditions where supplemental irrigation is available,
      irrigation may make the difference between successful or failed restoration.
      However, increasing the availability of water through irrigation may result in
      poor plant adaptation to surviving arid conditions or only temporary success
      followed by failure once supplemental water is withdrawn. In this study,
      irrigation stimulated germination in the irrigated plots about a month earlier
      than the plots dependent on natural rainfall, but this had little lasting effect.
      Spring and summer irrigation did not improve survival compared to the plots
      receiving no supplemental water. The largest effect of irrigation was a reduction
      in survival of several species grown under irrigated conditions as compared to
      nonirrigated conditions. In plots where water was applied all year long a single
      species, Artemisia californica, represented nearly 100% of the species present at
      the end of two growing seasons. Irrigation may speed revegetation under some
      conditions, but was not very effective in establishing natural vegetation
      structure.

PMID- 10954807
TI  - Specific Conductance and pH as Indicators of Watershed Disturbance in Streams of
      the New Jersey Pinelands, USA.
AB  - / We used linear regression to independently and jointly relate specific
      conductance and pH measured at New Jersey Pinelands stream sites to the
      percentage of altered land in a watershed. Percentage altered land included
      developed and agricultural land uses and represented watershed disturbance for a
      given site. Median values calculated for a 2-year period (September 1992 through
      August 1994) characterized pH and specific conductance at the study sites. We
      found the relationships between the median values for both water-quality measures
      and percentage altered land for a site to be consistent across subregion and
      dominant altered-land use. Our results also demonstrated that the water
      quality/altered-land relationships developed using median values were similar to
      relationships developed using data from any single-sample period within the
      entire study period. Individually, pH and specific conductance explained 48% and
      56%, respectively, of the variability in watershed disturbance among study sites.
      The joint use of pH and specific conductance explained 79% of the watershed
      disturbance variability among sites. The joint use of these easily obtained water
      quality measures can provide a quick assessment of instream water-quality impacts
      from upstream watershed disturbance at any Pinelands stream site. Additionally, a
      range in pH and specific conductance, and hence a range in ambient water quality,
      can be predicted for a given altered-land percentage or a change in existing
      altered-land conditions.

PMID- 10954808
TI  - ENVIRONMENTAL AUDITING: Risk Assessment in the Face of Controversy: Tree Clearing
      and Salinization in North Queensland.
AB  - / Several lines of evidence were followed to assess the risk of salinization
      after tree clearing in the upper Burdekin River basin in north Queensland.
      Conceptual, biophysical process-based approaches (pedological interpretation,
      event tree analysis, one-dimensional water balance modeling, and Boolean spatial
      analysis) were compared to empirical methods and field evidence. The convergence
      of all lines of conceptual reasoning to the conclusion that there exists a risk
      of salinization in north Queensland, consistent with field evidence of naturally
      occurring waterlogging and salinity, strengthens the argument against tree
      clearing.

PMID- 10954809
TI  - The Decision-Identification Tree: A New NEPA Scoping Tool.
AB  - / No single methodology has been universally accepted for determining the
      appropriate scope of analysis for an environmental impact statement (EIS). Most
      typically, the scope of analysis is determined by first identifying actions and
      facilities that need to be analyzed. Once the scope of actions and facilities is
      identified, the scope of impacts is determined. Yet agencies sometimes complete
      an EIS only to discover that the analysis does not adequately support decisions
      that need to be made. Such discrepancies can often be traced to disconnects
      between scoping, the subsequent analysis, and the final decision-making process
      that follows. A new and markedly different approach-decision-based scoping
      provides an effective methodology for improving the EIS scoping process. Decision
      based scoping, in conjunction with a new tool, the decision-identification tree
      (DIT), places emphasis on first identifying the potential decisions that may
      eventually need to be made. The DIT provides a methodology for mapping
      alternative courses of action as a function of fundamental decision points. Once
      these decision points have been correctly identified, the range of actions,
      alternatives, and impacts can be more accurately assessed; this approach can
      improve the effectiveness of EIS planning, while reducing the risk of future
      disconnects between the EIS analysis and reaching a final decision. This approach
      also has applications in other planning disciplines beyond that of the EIS.

PMID- 10954811
TI  - A critical look at laparoscopic adjustable silicone gastric banding for surgical
      treatment of morbid obesity: does it measure up?

PMID- 10954812
TI  - Minimally invasive surgical staging for esophageal cancer.
AB  - BACKGROUND: The incidence of esophageal adenocarcinoma is increasing in the
      United States, and the 5-year survival rate is dismal. Preliminary data suggest
      that conventional imaging is inaccurate in staging esophageal cancer and could
      limit accurate assessment of new treatments. The objective of this study was to
      compare minimally invasive surgical staging (MIS) with conventional imaging for
      staging esophageal cancer. METHODS: Patients with potentially resectable
      esophageal cancer were eligible. Staging by conventional methods used computed
      tomography (CT) scan of the chest and abdomen, and endoscopic ultrasound (EUS),
      whereas MIS used laparoscopy and videothoracoscopy. Conventional staging results
      were compared to those from MIS. RESULTS: In 53 patients, the following stages
      were assigned by CT scan and EUS: carcinoma in situ (CIS; n = 1), I (n = 1), II
      (n = 23), III (n = 20), IV (n = 8). In 17 patients (32.1%), MIS demonstrated
      inaccuracies in the conventional imaging, reassigning a lower stage in 10
      patients and a more advanced stage in 7 patients. CONCLUSIONS: In 32.1% of
      patients with esophageal cancer, MIS changed the stage originally assigned by CT
      scan and EUS. Therefore, MIS should be applied to evaluate the accuracy of new
      noninvasive imaging methods and to assess new therapies for esophageal cancer.

PMID- 10954813
TI  - Laparoscopically assisted transsacral resection of rectal cancer with primary
      anastomosis. A preliminary review.
AB  - BACKGROUND: The management of rectal cancer has been changing to include more
      sphincter-sparing procedures. We report our initial experience with a new
      technique incorporating laparoscopy and a transsacral approach for low or
      midlevel rectal cancer. Here, we tried to determine whether this sphincter
      sparing method could produce acceptable morbidity and recurrence rates. METHODS:
      Patients with rectal cancer 4 to 8 cm from the dentate line underwent
      laparoscopically-assisted transsacral resection (LTR) with primary anastomosis.
      With this technique, the rectosigmoid is mobilized via laparoscopy while the
      patient is in the supine position. Next, the patient is placed in the prone
      jackknife position, and a segment of rectum is resected by a transsacral
      approach. Age, estimated blood loss, length of time in the operating room, length
      of stay, and postoperative complications were noted. Aspects of the tumor
      pathology regarding stage, lymph nodes, tumor size, and presence of tumor at
      resection margins also were recorded. RESULTS: A total of 13 patients, ages 26 to
      70 years (mean, 52.5 years), underwent the procedure. No perioperative deaths
      occurred. The mean hospital stay was 9.6 days. The average size of the rectal
      lesion was 4.3 cm in the largest dimension. The average specimen contained 11.5
      total, and 2.0 metastatic lymph nodes. Postoperative complications included two
      anastomotic breakdowns and two other wound complications. Late follow-up
      evaluation ranged from 10 to 30 months, with 11 of 13 patients alive (85%
      survival). Two local recurrences and three distant recurrences were noted at long
      term follow-up assessment. CONCLUSIONS: In selected patients with low or midlevel
      rectal cancer, LTR may be a viable option. Further experience is necessary to
      define its oncologic efficacy and whether routine temporary diverting colostomy
      is indicated.

PMID- 10954815
TI  - Long-term prognosis of gallbladder cancer diagnosed after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Several clinical and laboratory studies concerning port-site
      recurrence have raised the concern that laparoscopic procedures might worsen the
      prognosis of malignant disease. However, the long-term prognosis of patients with
      malignancy who undergo laparoscopic surgery is still unknown. The purpose of this
      study was to examine the long-term prognosis of patients with unexpected
      gallbladder cancer diagnosed after laparoscopic cholecystectomy (LC). METHODS: A
      clinicopathologic study was performed on 41 patients with postoperatively
      diagnosed gallbladder cancer from among 5,027 patients undergoing LC at 24
      institutions. The cumulative survival rate was compared with that reported for
      gallbladder cancer diagnosed after open cholecystectomy (OC). RESULTS: Of 26
      patients with early gallbladder cancer (pTis or pT1), 23 were simply followed up,
      and 9 of 15 patients with advanced cancer (pT2 or pT3) had additional resection
      after the diagnosis of gallbladder cancer. Port-site recurrence occurred in four
      patients, and two of them died of the cancer. However, at this writing, the other
      two are still alive after abdominal wall resection or radiation therapy, having
      survived for 31 and 71 months, respectively. The 5-year survival rate was 92% for
      early cancer and 59% for advanced cancer. These results were comparable with 5
      year survival rates for gallbladder cancer diagnosed after OC. CONCLUSIONS:
      Although port-site recurrence occurred in four patients with advanced gallbladder
      cancer, the long-term prognosis of patients with undiagnosed gallbladder cancer
      who underwent LC was not worsened by the laparoscopic procedure. We conclude that
      surgeons can perform LC with reasonable confidence, even if the lesion is
      possibly malignant.

PMID- 10954814
TI  - Use of a self-expanding stent in the palliation of rectal cancer recurrences. A
      report of three cases.
AB  - BACKGROUND: Patients with nonresectable rectal cancer recurrences and elderly
      high risk patients are currently given a colostomy as a palliative therapy. To
      improve the quality of life in these patients, we inserted a self-expanding metal
      stent to relieve the symptoms of obstruction caused by a rectal cancer
      recurrence. METHODS: Three patients (two male, one female; ages 61, 69, and 59),
      all suffering from a rectal cancer pelvic recurrence and diffuse metastases, had
      a stent inserted. Using fluoroscopic and endoscopic control, a metal guidewire
      was passed through the obstruction. A mild dilatation of the stenosis was carried
      out before positioning of the expandable metal stent. RESULTS: The procedure was
      successful at the first attempt in all the patients, and stool evacuation was
      immediate. Patients complained of rectal tenesmus during the first 48 h, which
      was treated with nonsteroid anti-inflammatory drugs. However, there were no
      serious complications related to the procedure. Regular endoscopic and clinical
      follow-up were carried out. No patient had any evidence of recurrent obstruction.
      CONCLUSION: In cases of inoperable rectal cancer recurrence, the placement of
      self-expanding metal stents is technically feasible and safe, and it avoids a
      permanent colostomy.

PMID- 10954816
TI  - Thoracoscopic splanchnicectomy for pain control in patients with unresectable
      carcinoma of the pancreas.
AB  - BACKGROUND: Intractable pain is the most distressing symptom in patients
      suffering from unresectable pancreatic carcinoma. Palliative interventions are
      justified to relieve the clinical symptoms with as little interference as
      possible in the quality of life. The purpose of this study was to examine the
      efficacy and safety of thoracoscopic splanchnicectomy for pain control in
      patients with unresectable carcinoma of the pancreas. METHODS: Between May 1995
      and April 1998, 24 patients (14 men and 10 women) with a mean age of 65 years
      (range, 30-85) suffering from intractable pain due to unresectable carcinoma of
      the pancreas underwent 35 thoracoscopic splanchnicectomies. All patients were
      opiate-dependent and unable to perform normal daily activities. Subjective
      evaluation of pain was measured before and after the procedure by a visual
      analogue score. The following parameters were also evaluated: procedure-related
      morbidity and mortality, operative time, and length of hospital stay. RESULTS:
      All procedures were completed thoracoscopically, and no intraoperative
      complications occurred. The mean operative time was 58+/-22 min for unilateral
      left splanchnicectomy and 93.5+/-15.6 min for bilateral splanchnicectomies. The
      median value of preoperative pain intensity reported by patients on a visual
      analogue score was 8.5 (range, 8-10). Postoperatively, pain was totally relieved
      in all patients, as measured by reduced analgesic use. However, four patients
      experienced intercostal pain after bilateral procedures, even though their
      abdominal pain had disappeared. Complete pain relief until death was achieved in
      20 patients (84%). Morbidity consisted of persistent pleural effusion in one
      patient and residual pneumothorax in another. The mean hospital stay was 3 days
      (range, 2-5). CONCLUSIONS: We found thoracoscopic splanchnicectomy to be a safe
      and effective procedure of treating malignant intractable pancreatic pain. It
      eliminates the need for progressive doses of analgesics, with their side effects,
      and allows recovery of daily activity. The efficacy of this procedure is of major
      importance since life expectancy in these patients is very short.

PMID- 10954817
TI  - Laparoscopic-assisted vs. open ileocolic resection for Crohn's disease. A
      comparative study.
AB  - BACKGROUND: The objective of this study was to compare laparoscopic-assisted
      ileocolic resection for Crohn's disease of the distal ileum with open surgery in
      two consecutive groups of patients. METHODS: From 1995 until 1998, 48 patients
      underwent open ileocolic resection at the Academic Medical Center (AMC) in
      Amsterdam, while 30 patients had laparoscopic-assisted ileocolic resection at the
      Leiden University Medical Center (LUMC). Patient characteristics, perioperative
      course, and recovery were compared. Differences between the groups were tested
      using Student's t-test for independent groups and chi-square tests when
      appropriate. RESULTS: The open and the laparoscopic patient groups were
      comparable for age, gender, body mass index (BMI), prior abdominal surgery, and
      length of resected bowel. The conversion rate was 6.6%. Laparoscopic operating
      times (138+/-SD 36 min) were significantly longer than those observed in the open
      group (104+/-SD 34 min). Discharge was significantly earlier in the laparoscopic
      group than the open group (5.7 vs 10.2 postoperative days, p<0.007).
      Postoperative morbidity did not differ significantly between the patients treated
      traditionally (14.6%) and laparoscopically (10%). CONCLUSION: Compared to open
      surgery, laparoscopic ileocolic resection for Crohn's disease is associated with
      similar morbidity rates, a shorter hospital stay, and improved cosmetic results,
      justifying the laparoscopic approach as the procedure of choice.

PMID- 10954818
TI  - Laparoscopic elective treatment of diverticular disease. A comparison between
      laparoscopic-assisted and resection-facilitated techniques.
AB  - BACKGROUND: Because of the presence of significant inflammatory reaction,
      elective surgical laparoscopic-assisted treatment of complicated diverticular
      disease can be difficult, leading to a high conversion and complication rate.
      Laparoscopic alternatives to this assisted approach consist of the hand-assisted
      method and the more conventional facilitated laparoscopic sigmoid resection.
      Facilitated laparoscopic sigmoid resection implies laparoscopic mobilization of
      the sigmoid as much as possible and splenic flexure when called for. Through a
      Pfannenstiel incision, the difficult steps of the operation-such as the
      dissection of the inflammatory process and taking down the fistula, but also
      resection and manual anastomosis-can be performed. In this study, we compare the
      operating time, conversion rate, complications, and costs of both assisted and
      resection-facilitated techniques. METHODS: We compared two consecutive series of
      35 patients with diverticular disease who underwent a sigmoid resection by
      laparoscopy. Both groups were comparable in terms of age, gender, and kind of
      complicated diverticular disease. RESULTS: The operating time, conversion rate,
      and costs were all less in the laparoscopic-facilitated group. The fact that
      there were no conversions in this group is the most important finding of this
      study. Not only was it possible to convert from the assisted laparoscopic
      approach to laparotomy (five patients of 35), it was also possible to convert
      from the assisted to the facilitated form (seven of 35 patients). CONCLUSIONS:
      Laparoscopic-facilitated sigmoid resection is a feasible intervention for all
      forms of complicated diverticular disease and yields marked reductions in
      operating time, conversion rate, and operative and general costs.

PMID- 10954819
TI  - The cutaneous nerves encountered during laparoscopic repair of inguinal hernia:
      new anatomical findings for the surgeon.
AB  - BACKGROUND: With an incidence rate of 2%, injury to the nerves of the lumbar
      plexus is the most common complication of laparoscopic hernioplasty, particularly
      when the transabdominal preperitoneal (TAPP) technique is used. METHODS: The
      course of the genitofemoral nerve, lateral femoral cutaneous nerve, and
      ilioinguinal nerve within the operation site was investigated in 53 adult
      dissecting-room bodies. Their relationship to the deep inguinal ring, iliopubic
      tract, and anterior superior iliac spine was also examined. RESULTS: Both the
      femoral and genital branches of the genitofemoral nerve may penetrate the
      abdominal wall lateral to the deep ring and cranial to the iliopubic tract. The
      lateral femoral cutaneous nerve and the ilioinguinal nerve may run immediately
      lateral to the anterior superior iliac spine. CONCLUSION: Contrary to the
      previously accepted opinion, dissection and the placement of staples either
      cranial to the iliopubic tract or lateral to the anterior superior iliac spine
      can result in injury to the nerves.

PMID- 10954820
TI  - The femoral hernia: an ideal approach for the transabdominal preperitoneal
      technique (TAPP).
AB  - BACKGROUND: We designed a study to determine the rate of intra- and postoperative
      complications as well as the rate of recurrences in elective operated femoral
      hernias treated via the laparoscopic technique. METHODS: Between 1993 and 1998,
      we performed 1,097 operations in our department using the laparoscopic
      transabdominal preperitoneal (TAPP) technique. Femoral hernias amounted to only
      4.6% (51 cases) of these patients. The male/female ratio was 1:2. The data
      concerning the operations and pre- and postoperative treatment were recorded
      prospectively. The patients were followed up at 2 weeks and 1 year after the
      operation. RESULTS: We encountered one intraoperative bladder lesion, one
      subcutaneous port site infection, two postoperative hematomas that required
      reoperation, and two nerve irritation syndromes, which disappeared spontaneously
      after 6 months. Two patients developed an ileus; one required laparoscopic
      reintervention, and the other was treated with conventional open reoperation and
      intestinal resection. There were no recurrences. CONCLUSIONS: The application of
      the laparoscopic approach to the treatment of femoral hernias using the TAPP
      technique in nonemergency situations is highly effective. To date, we have seen
      no recurrences. Although the rate of major complications is low, current surgical
      techniques need to be perfected to avoid the type of complication recognized in
      this study.

PMID- 10954821
TI  - Laparoscopy in the management of gastric submucosal tumors.
AB  - BACKGROUND: Gastric tumors, including early gastric cancers, can be safely
      removed laparoscopically. They do not require an open laparotomy. METHODS: From
      March 1995 to December 1998, we used laparoscopy to resect gastric submucosal
      lesions in 32 patients. There were 22 men and 10 women. The patients ranged in
      age from 23 to 67 years (median, 51.4 yr). The lesions were located in the upper
      third in one patient, in the middle third in 20 patients, and in the lower third
      in 11 patients. The tumors ranged in size from 2 to 6 cm in diameter. The
      operative procedures were wedge resection in 19 patients, wedge resection with
      gastrotomy in two patients, intragastric surgery in nine patients, intragastric
      surgery with gastrotomy in one patient, and proximal gastrectomy in one patient,
      using a four- or five-port technique. The exophytic mass was resected with an
      Endo-GIA, and the tumors on the mucosal surface were exposed via a gastrotomy and
      excised. The gastrotomy was closed with an intracorporeal suture. In all cases,
      the operation was finished after the confirmation of tumor-free margins on frozen
      section biopsy specimens. RESULTS: The duration of the operation ranged from 80
      to 180 mins. The final pathologic findings were leiomyoma in 24 patients,
      adenomyoma in three patients, hyperplastic polyp in two patients, lipoma in one
      patient, hamartoma in one patient, and leiomyosarcoma in one patient. One case
      (3.1%) was converted to a mini-laparotomy due to technical difficulty; in one
      other case, more margin was resected laparoscopically due to the tumor-positive
      margin; and in one further patient, leakage was repaired by laparoscopic suturing
      on the 1st postoperative day. There were no other major complications and no
      deaths. The hospital stay ranged from 6 to 7 days. The maximum follow-up to date
      in these patients, including a case of leiomyosarcoma, was 42 months. There has
      been no evidence of tumor recurrence. CONCLUSION: The application of laparoscopy
      to submucosal tumors of the stomach is technically feasible, safe, and useful. It
      should be considered a viable alternative to open surgery and gastroscopic
      management because of its low invasiveness and good postoperative results.

PMID- 10954822
TI  - Laparoscopic esophagomyotomy with posterior partial fundoplication for primary
      esophageal motility disorders.
AB  - BACKGROUND: The outcomes of a laparoscopic esophagomyotomy with posterior partial
      fundoplication were compared between groups of patients with primary motility
      disorders. METHODS: In this study, 47 patients (26 women and 21 men, ages 24 to
      77 years; mean, 47 years) with significant dysphagia or chest pain who failed
      conservative treatment underwent a laparoscopic esophagomyotomy and posterior
      partial fundoplication. Preoperative evaluation revealed four groups of primary
      motility disorders: achalasia (n = 12), nutcracker esophagus (n = 12),
      hypertensive lower esophageal sphincter (LES) (n = 16), and diffuse esophageal
      spasm (n = 7). Statistical analysis was performed by Cramer's V test. RESULTS:
      Average follow-up period was 30.3 months. There was no mortality or early
      morbidity. Late morbidity included dysphagia or chest pain over 6 weeks in 10
      patients (21%), recurrent gastroesophageal reflux disease (GERD) in 3 patients
      (6%), and recurrent motility disorder in 2 patients (4%). Overall, 94% of the
      patients ultimately had complete resolution of dysphagia or chest pain. There was
      no significant difference in outcomes between groups. CONCLUSION: Early results
      suggest that laparoscopic esophagomyotomy with posterior partial fundoplication
      provides safe and effective relief from dysphagia and chest pain in patients with
      each of the primary motility disorders.

PMID- 10954823
TI  - Geometry and reproducibility in 360 degrees fundoplication.
AB  - BACKGROUND: In this study, we set out to precisely define two symmetrical points
      a on the anterior fundic wall and b on the posterior fundic wall. These points,
      when advanced around a 60-Fr bougie-filled esophagus, will meet on the right
      side, to the right of the anterior vagus nerve, to create a reliable,
      reproducible, loose (i.e., or "floppy") 360 degrees fundoplication (FP). METHODS:
      For the terms of this study, circumference = c; diameter = d; c/d = pi; pi =
      3.14; and d(cm) = Fr/30. Using a flexible plastic ruler, we measured, in cadavers
      (n = 5) and intraoperatively (n = 16), esophageal c at the gastroesophageal
      junction (GEJ) with a 60-Fr bougie in place; d was calculated from c. RESULTS:
      The smallest measured value for c was 7.5 cm (d = 2.39 cm); the largest value for
      c was 10.0 cm (d = 3.18 cm). The mean value was 8.35 cm (d = 2.66 cm). Points a
      and b are established by measuring laterally from a point where the greater curve
      meets the GEJ in the bougie-filled esophagus. Point a is 6.0 cm laterally and 6.0
      cm below the short gastric vessels on the anterior fundus; point b is 6.0 cm
      laterally in a symmetrical position on the posterior fundus. Connecting these
      three points as a line defines the inner c of the completed FP and measures 12.0
      cm. This gives an internal d of 3.82 cm for the FP. This is >1 cm larger than d
      for the mean measured external esophageal c of 8.35 cm where d = 2.66 cm. This
      technique creates a correctly oriented, symmetrical, "floppy," true
      fundoplication. It avoids wrapping or twisting the fundus around the GEJ. The
      technique is easily taught and reproducible. CONCLUSIONS: Two points, measured a
      horizontal distance of 6.0 cm from the GEJ, symmetrically placed on the anterior
      (point a) and posterior (point b) fundus can be brought anterior (a) and
      posterior (b) to the esophagus and sutured to the right of the anterior vagus
      nerve to reliably and reproducibly create a "floppy" 360 degrees fundoplication.

PMID- 10954824
TI  - Laparoscopic cholecystectomy for acute cholecystitis: can the need for conversion
      and the probability of complications be predicted? A prospective study.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) in acute cholecystitis is
      associated with a relatively high rate of conversion to an open procedure as well
      as a high rate of complications. The aim of this study was to analyze
      prospectively whether the need to convert and the probability of complications is
      predictable. METHODS: A total of 215 patients undergoing LC for acute
      cholecystitis were studied prospectively by analyzing the data accumulated in the
      process of investigation and treatment. Factors associated with conversion and
      complications were assessed to determine their predictive power. RESULTS:
      Conversion was indicated in 44 patients (20.5%), and complications occurred in 36
      patients (17%). Male gender and age >60 years were associated with conversion,
      but these factors had no sensitivity and no positive predictive value. The same
      factors, together with a disease duration of >96 h, a nonpalpable gallbladder, a
      white blood count (WBC) of >18,000/cc(3), and advanced cholecystitis, predicted
      conversion with a sensitivity of 74%, a specificity of 86%, a positive predictive
      value of approximately 40%, and a negative predictive value of 96%. However,
      these data became available only when LC was underway. Male gender and a
      temperature of >38 degrees C were associated with complications, but these
      factors had no sensitivity and no positive predictive value. Progression along
      the stages of admission and therapy did not add predictive factors or improve the
      predictive characteristics. Male gender, abdominal scar, bilirubin >1 mg%,
      advanced cholecystitis, and conversion to open cholecystectomy were associated
      with infectious complications. Their sensitivity and positive predictive value
      remained 0 despite progression along the stages of admission and therapy.
      CONCLUSION: Although certain preoperative factors are associated with the need to
      convert a LC for acute cholecystitis, they have limited predictive power. Factors
      with higher predictive power are obtained only during LC. The need to convert can
      only be established during an attempt at LC. Preoperative and operative factors
      associated with total and infectious complications have no predictive power.

PMID- 10954825
TI  - Laparoscopic accessory splenectomy for recurrent idiopathic thrombocytopenic
      purpura and hemolytic anemia.
AB  - BACKGROUND: Laparoscopic splenectomy is an effective treatment for idiopathic
      thrombocytopenic purpura (ITP) and hemolytic anemia that has a remission rate of
      80-90%. In some patients in whom the disease persists or recurs, a diagnosis of
      accessory spleen is made. The long-term efficacy of laparoscopic accessory
      splenectomy is unknown. METHODS: Patients who underwent laparoscopic accessory
      splenectomy were followed in the outpatient clinic. The perioperative course,
      blood counts, and need for medical therapy to maintain a normal count were
      recorded. RESULTS: Eight patients underwent laparoscopic accessory splenectomy.
      All procedures were completed laparoscopically, and all patients were discharged
      on the 1st postoperative day. Patients were available for a follow-up period of
      15 months range, (3-27). None of the ITP patients achieved a complete remission.
      Two of them had a partial remission, and five ITP patients are now being treated
      with chronic corticosteroids to maintain a platelet count of >100,000/ml.
      CONCLUSION: Laparoscopic accessory splenectomy is associated with a low rate of
      morbidity and a short hospital stay. Despite its success in removing all residual
      splenic tissue, most patients will probably not enjoy a complete remission.

PMID- 10954828
TI  - Less traumatic abdominal wall retraction for gasless laparoscopic surgery.

PMID- 10954826
TI  - Laparoscopic interval appendectomy for periappendicular abscess.
AB  - BACKGROUND: Laparoscopic appendectomy was first described in the early 1980s and
      is currently widely used for the treatment of acute appendicitis. The application
      of laparoscopic techniques to interval appendectomy and the value of this
      procedure as compared to open elective interval appendectomy remains uncertain.
      Therefore, we set out to assess the usefulness of interval laparoscopic
      appendectomy following periappendicular abscess. METHODS: This study analyzes the
      data for 10 patients who underwent interval laparoscopic appendectomy 8-10 weeks
      following documented periappendicular abscess in the period between January 1996
      and June 1998. RESULTS: Laparoscopic appendectomy was completed successfully in
      all 10 patients. Nine patients were discharged 1 day after the operation; one
      patient was discharged on the evening of the operative day. There were no
      complications and no wound infections. CONCLUSION: We conclude that the
      laparoscopic approach is the preferable treatment for interval appendectomy. It
      is associated with minimal or no morbidity and a very short hospital stay.

PMID- 10954829
TI  - Guidelines for the clinical application of laparoscopic biliary tract surgery.
      Society of American Gastrointestinal Endoscopic Surgeons.

PMID- 10954830
TI  - News and notices

PMID- 10954831
TI  - Classical conditioning of responses to an artificial nipple in the rat fetus: mu
      and kappa opioid systems.
AB  - The rat fetus exhibits oral grasp responses when presented with an artificial
      nipple in utero. Preexposure to milk produces a transient decrease in oral grasp
      responses. The effect of milk on oral grasping is mediated by endogenous activity
      in brain opioid systems. Specifically, milk triggers mu activity in rostral brain
      regions and kappa opioid activity in caudal brain regions to decrease oral
      grasping of the artificial nipple. Reexposure to the artificial nipple after it
      has been paired with milk during a classical conditioning trial results in a
      conditioned reduction in oral grasping that is evident when fetuses are reexposed
      to the nipple. The classically conditioned decrease in oral grasping is mediated
      by mu opioid activity in rostral brain regions and kappa opioid activity in
      caudal brain regions. Endogenous opioid systems, activated by exposure to milk
      and the nipple, may regulate the processing of sensory information during
      suckling in the rat.

PMID- 10954832
TI  - Maturational changes in heart rate and heart rate variability in low birth weight
      infants.
AB  - To provide insight into the maturation of neural mechanisms responsible for
      variability in heart rate during quiet and active sleep, 6-hour continuous
      electrocardiographic recordings and simultaneous minute-by-minute behavioral
      activity state assignments were performed in 61 healthy, growing low birth weight
      infants. The infants weighed 795-1600 g at birth and ranged between 31-38 weeks
      in postconceptional age. During this age interval there was a decrease in heart
      rate during quiet sleep and an increase in both time domain and frequency domain
      measures of the variability in cardiac interbeat intervals. In quiet sleep,
      global variability, measured as SD of R-R intervals, increased in relation to
      age, as did higher frequency variability, measured as the square root of the mean
      of squared successive differences in R-R intervals. Developmental changes in the
      0.5-2.0 Hz spectral power band of RR-interval variability, another measure of
      high frequency variability, paralleled the changes seen in the time domain
      measure. Evaluation of patterns of changes in the magnitude and direction of
      successive interbeat intervals provided evidence that the incidence of sustained
      accelerations or decelerations increased whereas the incidence of no change in
      consecutive RR-intervals decreased as infants matured. Among the various measures
      of heart rate variability, the incidence of sustained change and no change in
      successive interbeat intervals were most closely related to postconceptional age
      in both sleep states. The overall decrease in heart rate, increase in heart rate
      variability, and increase in the pattern of changes in interbeat interval with
      postconceptional age are consistent with the maturation of the autonomic cardio
      regulatory activity from 31-38 weeks age.

PMID- 10954833
TI  - The effect of oral-gustatory, tactile-bucal, and tactile-manual stimulation on
      the behavior of the hands in newborns.
AB  - The effect of stimulation (oral-gustatory with sucrose, tactile-bucal, and
      tactile-manual) on the frequency of hand contact with the oral (hand-mouth and
      hand sucking) and perioral (hands near the mouth) regions was compared in 24 full
      term newborns. The 16-minute evaluation was divided into four equal periods,
      without intervals: (A) Baseline, no stimulation applied; (B) tactile-bucal, the
      newborn was allowed to suck the distal phalange of the researcher's little
      finger; (C) tactile-manual, the newborn was allowed to grasp the researcher's
      index finger; (D) 0.3 ml sucrose solution was administered orally to the
      newborns. After every three newborns were tested, the sequence of stimulation
      application was changed. The frequencies of the hand behaviors were calculated.
      It was observed that the sucrose significantly increased the frequency of hand
      sucking (p<0.05). Sucrose was, therefore, the most effective stimulus for
      eliciting the behavior of hand sucking.

PMID- 10954834
TI  - Enhanced intake of ethanol in preweanling rats following interactions with
      intoxicated siblings.
AB  - Recently Hunt, Holloway, & Scordalakes (1999) described a novel procedure for
      examining how social interactions with an intoxicated sibling can enhance
      periadolescent rats' voluntary intake of ethanol. In the present series of
      experiments we extend these findings to preweanlings. In Experiment 1, same-sex
      sibling 16-day-olds were assigned to be either (a) a demonstrator that was
      administered 1.5 g/kg ethanol or water control or (b) an observer that was tested
      for ethanol intake following a brief interaction with the demonstrator. Observers
      interacting with EtOH demonstrators exhibited increased intake of ethanol
      relative to observers interacting with water demonstrators. In Experiment 2,
      subjects were 8, 12, or 16 days of age and at all ages, ethanol intakes increased
      following exposure to an intoxicated sibling. In Experiment 3, repeated exposures
      to ethanol demonstrators on days 12, 14, and 16 was found to promote ethanol
      intake after weaning (on postnatal day 22). Collectively these data indicate that
      exposure to ethanol cues in the context of home/social cues can lead to
      modifications in ethanol acceptance, and that repeated exposures to such cues
      during infancy can impact ethanol ingestion after weaning.

PMID- 10954835
TI  - Development of spontaneous stereotyped behavior in deer mice: effects of early
      and late exposure to a more complex environment.
AB  - Abnormal repetitive behaviors such as stereotypies are associated with
      neurodevelopmental disorders and are often observed under conditions of
      environmental restriction, particularly early in development. Few studies,
      however, have systematically assessed the effects of environmental enrichment and
      almost no information is available as to whether a sensitive period exists for
      such enrichment effects. We hypothesized that spontaneous stereotypies exhibited
      by deer mice housed under standard laboratory conditions were the result of
      environmental restriction and that a sensitive period exists for the
      development/prevention of stereotypies. Exposure to a more complex environment
      early in the post-weaning period resulted in substantially less stereotypy in the
      complex environment. Importantly, this outcome was maintained even after mice
      were housed in standard cages for an identical period of time. Later exposure to
      the more complex environment also resulted in significantly lower levels of
      stereotypy compared to controls. These effects were observed in the experimental
      housing condition as well as in a standard test context. The effects of early and
      late enrichment support the importance of environmental restriction in the
      genesis of stereotype and provide support for the efficacy of early and late
      enrichment in the prevention of stereotypies.

PMID- 10954836
TI  - Ontogeny of spatial discrimination in mice: a longitudinal analysis in the
      modified open-field with objects.
AB  - The present longitudinal study investigated the emergence of spatial
      discrimination and reaction to novelty in CD-1 mice, using a modified open-field
      test with four objects, a test in which responses to both spatial rearrangement
      of familiar objects and object novelty are assessed. Male and female mice were
      tested on postnatal days (pnd) 18, 28, 46 and 90. Locomotor activity was highest
      on pnd 90, whereas time spent on objects before rearrangement was highest on pnd
      46. Eighteen-day old mice were unable to detect both object rearrangement and
      object novelty, suggesting immaturity in processing spatial information. On days
      28 and 46 mice showed a clear response to object novelty, actively exploring the
      unfamiliar object placed in the arena, while at these ages object displacement
      elicited a generalized increase of exploration, not directed towards the
      displaced objects. A clear and selective response to object displacement emerged
      only at adulthood (day 90).

PMID- 10954837
TI  - Tyrosine hydroxylase-expressing and/or aromatic L-amino acid decarboxylase
      expressing neurons in the mediobasal hypothalamus of perinatal rats:
      differentiation and sexual dimorphism.
AB  - In this quantitative and semiquantitative immunocytochemical study, the authors
      evaluated the differentiation of neurons expressing tyrosine hydroxylase (TH)
      and/or aromatic L-amino acid decarboxylase (AADC) in the mediobasal hypothalamus
      (MBH) of male and female rats on embryonic day 18 (E18), E20, and postnatal day 9
      (P9). Four neuronal populations were distinguished according to either enzyme
      expression or neuron location. The earliest and most prominent first population
      was represented by TH-immunoreactive (IR)/AADC-immunonegative (IN) neurons that
      were detected initially at E18 and always were located in the ventrolateral
      region of the MBH. The second population of TH-IN/AADC-IR neurons was observed
      first at E20 and, after that time, was distributed dorsomedially. The third minor
      population of TH-IR/AADC-IR neurons initially was detected at E20 and was located
      dorsomedially. The fourth population was represented by TH-IR/AADC-IN neurons
      that were distributed in the dorsomedial region at any studied age. The numbers
      of TH-IR and AADC-IR neurons increased from their initial detection at E18 and
      E20 until P9. The area of TH-IR and AADC-IR neurons also increased from E18 to
      E20 and from E20 to P9, respectively. Both TH-IR and AADC-IR neurons showed sex
      differences in the neuron number, size, and optic density (OD). The numbers of TH
      IR neurons in males exceeded those of females at E20 and at P9, although, at P9,
      sexual dimorphism was a characteristic only of the ventrolateral population. The
      area and OD of TH-IR neurons from females exceeded those from males in the entire
      mediobasal hypothalamus (MBH) at E18 and E20 but only in its dorsomedial region
      at P9. Sexual dimorphism also was an attribute of AADC-IR neurons at E20 and P9.
      Their number, size, and OD were significantly higher in females than in males.
      Thus, the MBH of perinatal rats contained two major populations of TH-IR/AADC-IN
      or TH-IN-AADC-IR neurons and a minor population of TH-IR/AADC-IR neurons. The
      differentiating neurons expressing either enzyme showed sexual dimorphism.

PMID- 10954838
TI  - Calretinin in the entorhinal cortex of the rat: distribution, morphology,
      ultrastructure of neurons, and co-localization with gamma-aminobutyric acid and
      parvalbumin.
AB  - Calretinin is a marker that differentially labels neurons in the central nervous
      system. We used this marker to distinguish subtypes of neurons within the general
      population of neurons in the entorhinal cortex of the rat. The distribution,
      morphology, and ultrastructure of calretinin-immunopositive neurons in this
      cortical area were documented. We further analyzed the co-localization of the
      marker with gamma-aminobutyric acid (GABA) and studied whether calretinin
      positive neurons project to the hippocampal formation. Methods used included
      single-label immunocytochemistry at the light and electron microscopic level,
      retrograde tracing combined with immunocytochemistry, and double-label confocal
      laser scanning microscopy (CLSM). The entorhinal cortex contained calretinin
      positive cells in a scattered fashion, in all layers except layer IV (lamina
      dissecans). Bipolar and multipolar dendritic configurations were present,
      displaying smooth dendrites. Bipolar cells had a uniform morphology whereas the
      multipolar calretinin cell population consisted of large neurons, cells with long
      ascending dendrites, horizontally oriented neurons, and small spherical cells.
      Retrograde tracing combined with immunocytochemistry showed that calretinin is
      not present in cells projecting to the hippocampus. Few synapic contacts between
      calretinin-positive axon terminals and immunopositive cell bodies and dendrites
      were seen. Most axon terminals of calretinin fibers formed asymmetrical synapses,
      and immunopositive axons were always unmyelinated. Results obtained in the CLSM
      indicate that calretinin co-exists in only 18-20% of the GABAergic cell
      population (mostly small spherical and bipolar cells). Thus, the entorhinal
      cortex contains two classes of calretinin interneurons: GABA positive and GABA
      negative. The first class is presumably a classical, GABAergic inhibitory
      interneuron. The finding of calretinin-immunoreactive axon terminals with
      asymmetrical synapses suggests that the second class of calretinin neuron is a
      novel type of a (presumably excitatory) interneuron.

PMID- 10954839
TI  - Expression patterns of connexin genes in mouse retina.
AB  - To analyze the molecular basis of gap junctional communication in mouse retina,
      we examined the expression pattern of the following 13 connexin (Cx) genes: Cx26,
      Cx30, Cx30.3, Cx31, Cx31.1, Cx32, Cx36, Cx37, Cx40, Cx43, Cx45, Cx46, and Cx50.
      By using reverse transcriptase-polymerase chain reactions with primer
      oligonucleotides to murine connexin genes, we detected mRNAs of Cx26, Cx31, Cx32,
      Cx36, Cx37, Cx40, Cx43, Cx45, and Cx50. Retinae from heterozygous mice with
      targeted replacement of most of the Cx45 open reading frame by a lacZ reporter
      gene showed Cx45 promoter activity in somata of the ganglion cell layer and the
      inner nuclear layer. Immunoblot and immunofluorescence analyses with antibodies
      generated to murine connexin epitopes revealed the presence of Cx36, Cx37, Cx43,
      and Cx45 proteins: The outer and inner plexiform layer were immunopositive for
      Cx36 and Cx45. Cx37 immunoreactivity was found in blood vessels of the inner
      retina. Cx43 immunolabeling was detected in the ganglion cell layer and nerve
      fiber layer where it was largely colocalized with immunostaining of glial
      fibrillary acidic protein suggesting that Cx43-positive cells could be of glial
      origin. No Cx26 protein was detected in retina by using Cx26 antibodies for
      immunoblot analyses or confocal microscopy. Furthermore, comparative
      immunofluorescence analyses of retinae from mice deficient for Cx31, Cx32, or
      Cx40 with retinae of wild-type mice revealed no specific immunostaining. Our
      results demonstrate regional specificity in expression of connexin genes in mouse
      retina and, thus, provide a basis for future assignments of functional defects in
      connexin-deficient mice to cells in different regions of the retina.

PMID- 10954841
TI  - Development of salt-responsive neurons in the nucleus of the solitary tract.
AB  - The rodent gustatory system has become a popular and useful model for the study
      of brain development because of this system's protracted period of postnatal
      maturation and its sensitivity to subtle changes in the animal's sensory
      environment. The goal of this investigation was to improve our understanding of
      dendritic remodeling exhibited by second-order gustatory neurons by presenting a
      comprehensive and definitive description of the development of the dendritic
      architecture of taste-sensitive neurons in the rostral nucleus of the solitary
      tract. Extracellular and intracellular recording and intracellular labeling
      techniques were used to examine the structure and function of individual
      gustatory neurons in three groups of rats: (1) Postnatal day 13-21 (PND13-21),
      (2) Postnatal day 22-28 (PND22-28), and (3) Adult (postnatal day 60-90). We found
      that neurons that responded to all three of the salts in our taste array ("Salt
      Sensitive") exhibited a striking increase in the number of dendritic branch
      points, maximum branch order, swelling density, and spine density between the
      PND13-21 and PND22-28 periods. These increases were followed by a period of
      dendritic remodeling during which the values for all measures except spine
      density decreased significantly. The neurons that did not respond to all three
      salts exhibited no change in the number of dendritic branches, branch order, or
      spine density during development, but they did undergo a decrease in swelling
      density. We also found that there was a significant decrease in the total
      dendritic length and cell volume of Salt Sensitive neurons between the PND22-28
      and Adult periods, whereas the cells that did not respond to all three salts
      exhibited an increase in dendritic length and cell volume between postnatal day
      28 and adulthood. Finally, we found that the dendrites of the Adult Salt
      Sensitive neurons were more restricted in the rostrocaudal axis than either the
      PND13-21 or PND22-28 Salt Sensitive cells. In contrast, there were no significant
      changes in the rostrocaudal extent of the dendritic arbors of cells that did not
      respond to all three salts. When viewed in the context of the extant literature
      and our own preliminary studies that used modified salt diets, we propose that
      these results provide strong support for the hypothesis that there is a
      relationship between postnatal dendritic development (particularly remodeling)
      and the animal's sensitivity to salts.

PMID- 10954840
TI  - Differential effects of NGF and NT-3 on embryonic trigeminal axon growth
      patterns.
AB  - We examined the effects of neurotrophins nerve growth factor (NGF) and
      neurotrophin-3 (NT-3) on trigeminal axon growth patterns. Embryonic (E13-15)
      wholemount explants of the rat trigeminal pathway including the whisker pads,
      trigeminal ganglia, and brainstem were cultured in serum-free medium (SFM) or SFM
      supplemented with NGF or NT-3 for 3 days. Trigeminal axon growth patterns were
      analyzed with the use of lipophilic tracer DiI. In wholemount cultures grown in
      SFM, trigeminal axon projections, growth patterns, and differentiation of
      peripheral and central targets are similar to in vivo conditions. We show that in
      the presence of NGF, central trigeminal axons leave the tract and grow into the
      surrounding brainstem regions in the elongation phase without any branching. On
      the other hand, NT-3 promotes precocious development of short axon collaterals
      endowed with focal arbors along the sides of the central trigeminal tract. These
      neurotrophins also affect trigeminal axon growth within the whisker pad.
      Additionally, we cultured dissociated trigeminal ganglion cells in the presence
      of NGF, NT-3, or NGF+NT-3. The number of trigeminal ganglion cells, their size
      distribution under each condition were charted, and axon growth was analyzed
      following immunohistochemical labeling with TrkA and parvalbumin antibodies. In
      these cultures too, NGF led to axon elongation and NT-3 to axon arborization. Our
      in vitro analyses suggest that aside from their survival promoting effects, NGF
      and NT-3 can differentially influence axon growth patterns of embryonic
      trigeminal neurons.

PMID- 10954842
TI  - Importance of timing of olfactory receptor-axon outgrowth for glomerulus
      development in Manduca sexta.
AB  - In the moth Manduca sexta, development of glomeruli in the antennal (olfactory)
      lobes (ALs) follows a precise timetable and involves interactions of olfactory
      receptor cell (ORC) axons with AL glial cells and neurons. To study the
      importance of timing for these intercellular interactions, we experimentally
      desynchronized the development of the ALs and the ORCs by altering the
      temperature of the developing antenna and brain for defined periods of time
      during development. Selective cooling of the antenna relative to the body
      resulted in a delay of ORC-axon outgrowth, and slightly warming the antenna while
      cooling the body caused precocious ingrowth of axons into the AL. Whereas cooling
      of the antenna for 24 hours caused only a delay in the formation of glomeruli,
      cooling for 48 hours led to significant disruption of glomerular development.
      Glial cells did not form normal glomerular borders, and glomeruli were shaped
      abnormally. Axons of pheromone-specific ORCs projected to their correct target,
      but terminal branches within the macroglomerular complex (MGC) were not clearly
      segregated. The results suggest that proper formation of glial glomerular borders
      requires interaction of ORC axons and glial cells within a sensitive period,
      whereas targeting of ORC axons appears to be effective over extended periods in
      development. Precocious ingrowth of ORC axons after warming the antenna and
      cooling the body for 48 hours resulted in enlarged protoglomeruli. Glial borders
      formed normally, but a subpopulation of MGC-specific ORC axons grew past the MGC.
      The decreased accuracy of targeting in these cases suggests that targeting
      mechanisms are not fully developed before the time when ORC axons normally would
      enter the brain.

PMID- 10954843
TI  - Amine and amino acid transmitters in the eye of the mollusc Bulla gouldiana: an
      immunocytochemical study.
AB  - We identified putative transmitters of the photoreceptors and circadian pacemaker
      neurons and found candidates for efferent control in the eye of the marine
      mollusc Bulla gouldiana. Established antisera against octopamine, dopamine,
      serotonin, histamine, glutamate, gamma-aminobutyric acid (GABA), and taurine were
      used, and central ganglia were processed in parallel to evaluate general staining
      quality. Photoreceptors and circadian pacemaker cells both expressed
      immunoreactivity for glutamate and taurine. The eye and its sheath were devoid of
      GABA-like immunoreactive material, and none of the antisera directed against
      biogenic amines labelled cells or processes in the nervous tissue of the eye.
      However, dopamine and octopamine antisera stained large spherical granules
      (diameter 2-3 microm) contained in granular cells that are located in the
      connective tissue encapsulating the eye and the optic nerve. The serotonin
      antiserum revealed a sparse distribution of varicose axon fibers in the optic
      nerve and eye sheath. No histamine-immunoreactive processes were revealed in the
      eye. The functional significance of these findings for the molluscan eye and its
      circadian clock is discussed.

PMID- 10954844
TI  - Cells in the posterior thalamus project to both amygdala and temporal cortex: a
      quantitative retrograde double-labeling study in the rat.
AB  - Auditory information from the posterior thalamus reaches the lateral nucleus of
      the amygdala (LA) by way of two pathways: a direct thalamo-amygdala projection
      and a polysynaptic thalamo-cortico-amygdala projection. However, the quantitative
      extent of thalamic neurons that project to the LA or to the auditory association
      cortex (AAC) is not known. Furthermore, the extent and topographical distribution
      of bifurcating cells that project to both LA and AAC are also unknown. Therefore,
      separate tracers were injected into LA and either into all of AAC or within
      discrete regions of AAC, such as temporal areas TE3 or perirhinal cortex (PRh),
      and quantitative analyses were performed on labeling within the subregions of the
      auditory thalamus in rats. Following LA injections, retrogradely labeled cells
      were most numerous in the posterior intralaminar nucleus (PIN; 48.0% of all
      labeled thalamic cells), whereas labeled cells following injections of the entire
      AAC were most numerous in the dorsal division of the medial geniculate nucleus
      (MGd; 32.9% of all labeled thalamic cells). Following AAC injections localized to
      only TE3, the MGd again had the majority of labeled cells (35.9%), whereas
      following AAC injections localized to PRh, the PIN had the most labeled cells
      (32.8%). Double-labeled cells were found in all the thalamic regions studied and
      were most commonly observed in the PIN (43.7% of all double-labeled cells
      following injections into LA and throughout the AAC). The percentage of double
      labeled cells as a proportion of either LA-projecting or AAC-projecting cells
      varied among the thalamic nuclei studied, ranging from 2.9% up to 42.4%. The
      topographic distribution of double-labeled cells in the thalamic nuclei resembled
      that of single-labeled cells following LA injections more than single-labeled
      cells following AAC injection. These findings suggest that double-labeled cells
      contribute substantially to many of the direct thalamo-amygdala and indirect
      thalamo-AAC-amygdala projections. Among other functions, these bifurcating cells
      may help regulate the processing of input to the LA arriving from these two
      pathways to allow for certain types of plasticity in the LA during fear
      conditioning.

PMID- 10954845
TI  - Dopamine terminals synapse on callosal projection neurons in the rat prefrontal
      cortex.
AB  - Dopamine (DA) afferents to the prefrontal cortex (PFC) play an important role in
      the cognitive functions subserved by this cortical area. Within the PFC, DA
      terminals synapse onto the distal dendrites of both local circuit neurons and
      pyramidal projection cells. We have previously demonstrated in the rat PFC that
      some of the dendrites and spines postsynaptic to DA terminals arise from
      pyramidal neurons that project to the nucleus accumbens. However, it is not known
      whether the pyramidal cells that give rise to callosal intercortical connections
      of the PFC also receive DA synaptic input. To address this question, retrograde
      tract tracing using an attenuated strain of pseudorabies virus (PRV-Bartha) was
      combined with immunocytochemistry for tyrosine hydroxylase (TH) to identify DA
      terminals in the PFC. Thirty-six to 40 hours following injection of PRV into the
      contralateral PFC, numerous callosal projection neurons were extensively labeled
      throughout their dendritic trees, with no evidence of PRV trans-synaptic passage.
      In tissue prepared for electron microscopy, labeling for PRV was distributed
      throughout pyramidal cell somata and extended into distal dendrites and dendritic
      spines. Some PRV-labeled dendrites and spines received symmetric synaptic input
      from terminals containing peroxidase labeling for TH. These results demonstrate
      that DA terminals synapse onto the distal dendrites of callosally projecting PFC
      neurons and suggest substrates through which DA may modulate interhemispheric
      cortical communication.

PMID- 10954846
TI  - The neurofilament infrastructure of a developing presynaptic calyx.
AB  - Calyx-type synapses appear to be specifically designed to support fast, reliable,
      high-frequency excitatory transmission. In the chick ciliary ganglion, calyx
      terminals from preganglionic neurons in the midbrain form early in development on
      ciliary neurons. We find that labeling the calyx membranes with a lipophilic dye
      delivered by diffusion down the preganglionic nerve reveals a large membrane
      structure engulfing the postsynaptic cell by the end of embryogenesis. In
      contrast, labeling the calyces with a water-soluble dye by diffusion through the
      preganglionic nerve suggests large discontinuities in the calyx. A similar
      pattern of discontinuities is seen when presynaptic neurofilaments are labeled
      with antibodies selective for highly phosphorylated neurofilaments. The
      neurofilament infrastructure of the calyx first appears as a single thick bundle,
      which subsequently bifurcates during development and eventually generates a fine
      meshwork of filaments subdivided by several large neurofilament bundles
      encircling the postsynaptic cell body. The large bundles probably produce
      protruding ridges in the otherwise thin calyx cup, accounting for the disparity
      in staining patterns observed with membrane and cytosolic dyes. The postsynaptic
      membrane also undergoes restructuring during development with the appearance of
      large folded mats of somatic spines heavily invested with nicotinic receptors.
      The large presynaptic neurofilament bundles do not overlap the postsynaptic
      receptor clusters but do codistribute with large tracks of presynaptic
      microtubules. The neurofilament bundles may act as girders to provide structural
      support while at the same time defining conduits for microtubule-dependent
      transport of materials and rapid propagation of electrical signals throughout the
      extended calyx.

PMID- 10954847
TI  - Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the
      developing rat central nervous system.
AB  - Tyro-3, Axl, and Mer are three related receptor protein-tyrosine kinases (RPTKs)
      characterized by an extracellular domain exhibiting significant amino acid
      sequence similarity to neural cell adhesion molecules. The molecule Gas6 (for
      growth arrest-specific gene-6) has been shown to activate each of these
      receptors. Gas6 is expressed extensively in the central nervous system (CNS),
      suggesting that interactions between Gas6 and its receptors are likely to have
      physiologically relevant functions. To identify and localize the relevant
      Gas6/RPTK pairs, we have characterized the developmental expression of Tyro-3,
      Axl, and Mer in rat CNS using blotting and mRNA in situ hybridization analyses.
      Throughout development, Tyro-3 was the most widely expressed of the three
      receptors in the CNS, with Axl and Mer detected in only a limited number of sites
      in the adult. Tyro-3 expression was low in the embryo and increased markedly
      during early postnatal stages, with a time course paralleling that of
      synaptogenesis. Axl and Mer were expressed at low but relatively constant levels
      throughout development. In the cerebellum, all three receptors were found in
      Purkinje cells, and Tyro-3 was also detected in both granule neurons and Bergmann
      glia. Insofar as Gas6 has been previously shown to also be expressed by Purkinje
      cells, it may be engaged in both autocrine and paracrine signaling. The three
      receptors were also detected in cerebellar white matter, primarily during
      myelination. In the cortex, Tyro-3 was expressed at high levels during postnatal
      development and in the adult. Beginning at P6 in the hippocampus, Tyro-3 was
      expressed at high levels in CA1 pyramidal neurons and at lower levels in CA3 and
      was not detected in dentate granule neurons. Axl and Mer were found in the
      molecular layer of the dentate gyrus and were absent from the pyramidal and
      dentate granule neurons. In that Gas6 is expressed throughout the pyramidal cell
      layer, it may activate these cells in both an autocrine and a paracrine manner.
      These studies provide initial clues for elucidating the cellular functions of the
      Axl subfamily members and suggest potential complex Gas6/RPTK as well as
      RPTK/RPTK signaling interactions in the mature and developing CNS.

PMID- 10954849
TI  - Editorial

PMID- 10954848
TI  - Multiple ephrins regulate hippocampal neurite outgrowth.
AB  - Increasing evidence indicates that the eph family of ligands and receptors guides
      the formation of topographic maps in the brain through repulsive interactions.
      For example, we have recently found that in the hippocamposeptal system, the
      ligand ephrin-A2, which is expressed in an increasing gradient from dorsal to
      ventral septum, selectively induces pruning of topographically inappropriate
      medial hippocampal axons. The recent detection of ephrins A3 and A5, as well as
      A2, in the septum raised critical functional questions. Do the ligands act
      combinatorially, ensuring appropriate three-dimensional spatiotemporal
      projection, or do they exert entirely distinct actions in addition to guidance
      mechanisms? To approach these alternatives, we cloned mouse ephrin-A2 and
      compared the activities of the three ligands. Here, we show that these ligands
      reduce the number of hippocampal neurites in a similar fashion. The effect was
      regionally specific; medial hippocampal neurites were reduced 1.5- to 1.8-fold,
      whereas lateral hippocampal neurites were not significantly affected, conforming
      to topographic projection in vivo. Furthermore, we found that ephrins regulated
      neurite number in a stage-specific fashion, affecting E19 hippocampal neurites
      more than E16 neurites. Our observations suggest that all three septal ephrins,
      A2, A3, and A5, play spatiotemporally specific roles in guiding topographic
      projections from the hippocampus.

PMID- 10954850
TI  - Telomeres: more than chromosomal non-sticking ends.
AB  - Telomeres are specialized natural ends of eukaryotic chromosomes that, contrary
      to the ends of broken chromosomes, are stable and do not fuse with the ends of
      other chromosomes. In addition, telomeres protect chromosomal ends from
      degradation, facilitate completion of chromosomal DNA replication, and contribute
      to chromosome positioning within nuclei. Telomeric DNA consists of repetitive
      sequences and specific associated proteins, including the telomere repeat-binding
      factors TRF1 and TRF2. A lack of TRF2 enables end-to-end chromosome fusion. A
      structural disruption of telomeres not only causes chromosomal mechanical
      instability but also activates a programmed cell death cascade.

PMID- 10954852
TI  - Nuclear envelope associated protein that binds telomeric DNAs.
AB  - Rana temporaria oocytes at the 6th diplotene stage of maturation contain a
      special structure, the karyosphere capsule, with chromosomes covered and detached
      from the nuclear envelope (NE), though at the previous stage the telomeres were
      attached to the membrane, as characteristic of germ cells. The DNA-protein
      complexes from band shift assays with proteins extracted from oocyte NEs and
      telomeric DNA fragment (T(2)G(4))(130) were isolated and injected into a guinea
      pig. In the present paper the only protein of 70 kDa recognized by antibody (AB)
      in the NE is named the Membrane Telomere Binding Protein (MTBP). Western blots
      with guinea pig AB and AB against telobox peptide from TRF2 show that protein of
      60 kDa (probably TRF1) belongs to the chromatin, but MTBP (TRF2 according to
      immunoprecipitation) belongs to the NE. In the somatic cell nuclei both proteins
      are present and recognized by AB against telobox peptide, but AB raised recognize
      only MTBP/TRF2 due to the epitope different from telobox. Combined in situ
      hybridization with the vertebrate telomeric DNA sequences (T(2)AG(3))(135) and
      immunocytochemistry with the MTBP AB showed them to be colocalized within the
      mouse nucleus. As it was shown by immunofluorescense of NE spread, MTBP is
      organized in a distinct pattern that looks like a network made of double-dots.
      Electron microscope immunogold staining with both ABs showed that the protein is
      localized on the outer surface of the oocyte NE within cup-like structures
      attached to the membrane. This is the first clear evidence of a protein, which
      could be responsible for the attachment of telomeres to the nuclear membrane.

PMID- 10954851
TI  - Effects of three Sp1 motifs on the transcription of the FGF-4 gene.
AB  - Previous studies have shown that the transcription of the fibroblast growth
      factor-4 (FGF-4) gene is regulated by a powerful enhancer located approximately
      three kilobases downstream of the transcription start site. Several conserved cis
      regulatory elements in the promoter and the enhancer have been identified,
      including two Sp1 motifs located in the promoter and one Sp1 motif located in the
      enhancer. Each of these Sp1 motifs has been shown previously to bind the
      transcription factors Sp1 and Sp3 in vitro. The main objective of this study was
      to examine the potential interaction of the FGF-4 promoter and enhancer Sp1
      motifs. Using site-directed mutagenesis, we demonstrate that disruption of these
      sites, individually or in combination, reduce the expression of FGF-4
      promoter/reporter gene constructs in embryonal carcinoma cells. Importantly, we
      demonstrate that disruption of the enhancer Sp1 motif exerts a more pronounced
      effect on the expression of these constructs than disruption of the promoter Sp1
      motifs. We also demonstrate that changing the spacing and the stereo-alignment of
      the enhancer Sp1 motif, relative to the other cis-regulatory elements of the
      enhancer, has little effect on the ability of the enhancer to stimulate
      transcription. Furthermore, embryonic stem cells that contain two disrupted Sp1
      alleles were used to demonstrate that the transcription factor Sp1 is not
      necessary for expression of the endogenous FGF-4 gene. Finally, the significance
      of these findings relative to a looping model for the transcriptional activation
      of the FGF-4 gene is discussed.

PMID- 10954853
TI  - Expression, immunolocalization and sperm-association of a protein derived from
      24p3 gene in mouse epididymis.
AB  - The cDNA sequence for 24p3 protein in ICR mouse epididymal tissue was determined
      by PCR using primers designed according to the cDNA sequence derived from 24p3
      protein in mouse uterine tissue. In the present study, 24p3 protein was
      immunolocalized in the epithelial cells and lumen of mouse epididymis. Both
      immunoblot analysis for protein and northern blot analysis for mRNA level showed
      a declining gradient of 24p3 expression from the caput to caudal region of the
      epididymis. The 24p3 protein was undetectable in the testis. These findings
      suggest that the 24p3 protein is a caput-initiated secretory protein in the mouse
      epididymis. A postnatal study revealed that 24p3 gene expression occurred in mice
      at the age of 14 days, before the completion of epididymal differentiation. This
      expression remained at a constant level until epididymal differentiation was
      completed. We also found that the secreted 24p3 protein interacted predominantly
      with the acrosome of caudal spermatozoa. Our findings suggest that the epididymal
      24p3 protein is a caput-initiated and sperm-associated gene product and may be
      important in the reproductive system.

PMID- 10954854
TI  - Behavior of M-phase synchronized blastomeres after nuclear transfer in cattle.
AB  - M-phase synchronized bovine blastomeres were used to study the effect of nuclear
      cytoplasmic synchronization on the developmental potential after nuclear transfer
      (NT). The capacity of nocodazole and benomyl to reversibly synchronize
      blastomeres from embryos in M-phase was evaluated. Nocodazole reversibly arrested
      bovine embryos at the studied stages and induced high rates of M-phases in
      morulae and compact morulae. In contrast, benomyl was less efficient than
      nocodazole to synchronize in M-phase. After transfer of an M-phase blastomere,
      premature chromatin condensation was the prevalent finding 1 hr post-fusion
      (hpf). Condensed chromosomes non-arranged in the equatorial plate (1-3 hpf) that
      acquired an organized structure over time (3-7 hpf) were subsequently observed.
      Anaphase-telophase structures were predominantly recorded at 4-9 hpf. About 50%
      of the embryos activated at both 3-4 and 6-7 hpf extruded a polar body-like
      structure 5 hr after activation, but this was not observed in embryos activated
      immediately after fusion. A significantly lower activation rate was observed for
      oocytes activated 3-4 hpf compared to those activated 6-7 hpf. However, the
      ability to undergo first cleavage was significantly lower in the latter group.
      Reconstructed embryos activated immediately after fusion showed no difference in
      the rate of activation compared to those activated 6-7 hpf, although the cleavage
      rate was higher. DNA synthesis was observed at a significantly higher rate in
      embryos activated both immediately and 3-4 hpf that did not extrude a PB-like
      structure than in those activated 3-4 hpf that extruded a polar body-like
      structure. Under the conditions tested M-phase donor cells cannot be properly
      remodeled after NT in cattle to trigger normal embryonic development. Our
      observations of chromatin structures together with DNA synthesis suggest that the
      failure in the development may be due to improper chromatin remodeling of mitotic
      nuclei after NT, which may result in chromosomal abnormalities incompatible with
      normal embryo development.

PMID- 10954855
TI  - Potent and stage-specific action of glutathione on the development of goat early
      embryos in vitro.
AB  - The effect of glutathione (GSH) addition on the development of 1- or 2-cell goat
      early embryos in vitro was examined. Embryos were collected from superovulated
      Korean black goat (Capra hircus aegagrus) and cultured for 6 days in synthetic
      oviduct fluid medium supplemented with either bovine serum albumin (BSA) or
      serum. Without GSH addition, almost all embryos could not develop beyond 8- to 16
      cell block. However, GSH addition greatly improved in vitro development of early
      embryos to blastocyst stage, and its action was highly dependent on the presence
      and source of proteins supplemented into the culture medium. Among the protein
      supplemented cultures, GSH effect was most prominent in 10% FBS-supplemented
      culture, in which the proportion (91%) of blastocysts developed from early
      embryos was much higher than that of BSA- (42-64% depending on its content) or
      goat serum (GS)-supplemented cultures (21%), or even than that of somatic cell
      supported co-culture (60%). As well as in terms of the morphological development,
      mean cell number of blastocysts (185 +/- 12) developed from FBS condition was
      significantly higher than that of blastocysts developed from any other culture
      conditions and moreover comparable to that of blastocysts developed in vivo (190
      +/- 9). The viability of these blastocysts was finally confirmed by their term
      development (6/12) from embryo transfer. To delineate action time of GSH during
      embryo development, GSH was treated at 1-day intervals through 6-days culture
      periods excepting the last day. In the GSH-treated embryos at day 3 of culture,
      which corresponds to the time of in vitro 8- to 16-cell block stage, the
      proportion of blastocyst was markedly increased up to 77% of cultured embryos and
      conversely that of the arrested embryos was decreased to 7%. In the embryos
      treated later, however, their developmental potency decreased abruptly.
      Therefore, these results clearly demonstrated that GSH could greatly improve the
      in vitro development of goat early embryos by specifically acting on the 8- to 16
      cell block stage during in vitro development, suggesting that GSH may be one of
      the important regulators on the development of goat embryos in vivo.

PMID- 10954856
TI  - Birth of mice after nuclear transfer by electrofusion using tail tip cells.
AB  - Mice have been successfully cloned from cumulus cells, fibroblast cells,
      embryonic stem cells, and immature Sertoli cells only after direct injection of
      their nuclei into enucleated oocytes. This technical feature of mouse nuclear
      transfer differentiates it from that used in domestic species, where
      electrofusion is routinely used for nuclear transfer. To examine whether nuclear
      transfer by electrofusion can be applied to somatic cell cloning in the mouse, we
      electrofused tail tip fibroblast cells with enucleated oocytes, and then assessed
      the subsequent in vitro and in vivo development of the reconstructed embryos. The
      rate of successful nuclear transfer (fusion and nuclear formation) was 68.8%
      (753/1094) and the rate of development into morulae/blastocysts was 40.8%
      (260/637). After embryo transfer, seven (six males and one female; 2.5% per
      transfer) normal fetuses were obtained at 17.5-21.5 dpc. These rates of
      development in vitro and in vivo are not significantly different from those after
      cloning by injection (44.7% to morulae/blastocysts and 4.8% to term). These
      results indicate that nuclear transfer by electrofusion is practical for mouse
      somatic cell cloning and provide an alternative method when injection of donor
      nuclei into recipient oocytes is technically difficult.

PMID- 10954857
TI  - Comparative immunohistochemical distribution of connexin 37 and connexin 43
      throughout folliculogenesis in the bovine ovary.
AB  - Among gap junctional proteins previously identified in the mouse ovary, connexins
      (Cx) Cx37 and Cx43 appeared to be essential for normal follicular growth. The aim
      of this work was to detect Cx37 expression in the bovine ovary, then to quantify
      and compare its follicular distribution pattern with that of Cx43 using
      quantitative analysis of immunofluorescently labeled ovary sections viewed with a
      confocal laser scanning microscope. Cx37 immunoreactivity was detected in bovine
      ovarian follicles and was predominantly localized at preantral stages. Unlike
      follicular Cx43 expression which was restricted to granulosa cells, Cx37 staining
      was observed in both oocyte and granulosa cell compartments. While no changes
      were seen during early follicular growth, the level of Cx37 expression decreased
      significantly at the onset of antral cavity formation (P </= 0.01). On the
      contrary to what was found for Cx37, Cx43 was weakly expressed in preantral
      follicles. Concomitant with antrum formation, the level of Cx43 expression
      increased significantly (P </= 0.01). A further increase was correlated with
      antral follicular size (P </= 0.01). Cx43 immunoreactivity declined significantly
      in morphologically atretic follicles (P </= 0.01). A comparative analysis showed
      that Cx37 and Cx43 expression patterns were differentially regulated and could
      reflect specific physiological roles for each gap junction protein throughout
      folliculogenesis in cow.

PMID- 10954858
TI  - Mechanisms regulating norgestomet inhibition of endometrial gland morphogenesis
      in the neonatal ovine uterus.
AB  - In many species, endometrial gland adenogenesis occurs neonatally in an ovary-
      and steroid-independent manner. Chronic exposure of the developing neonatal ovine
      uterus to norgestomet (NOR) from birth permanently ablates endometrial gland
      morphogenesis or adenogenesis, creating an adult ovine uterine gland knockout
      (UGKO) phenotype. This study was conducted to determine the mechanism(s) whereby
      NOR inhibits adenogenesis in the neonatal ewe. Ewe lambs received no implant or a
      NOR implant at birth and on postnatal day (PND) 14, and they were necropsied on
      PND28. Histological analyses of the tracts indicated NOR exposure specifically
      inhibited endometrial adenogenesis, but no histoarchitectural differences were
      observed in the oviduct, cervix, or vagina. No effect of NOR treatment was
      detected on proliferating cell nuclear antigen (PCNA) expression in the
      endometrial luminal epithelium (LE), stroma, or myometrium. In control (CX) ewes,
      estrogen receptor alpha (ER-alpha) and progesterone receptor (PR) mRNA and
      protein were expressed strongly in nascent and proliferating glandular epithelium
      (GE) but were undetected in epithelium of NOR uteri. Expression of c-met and
      fibroblast growth factor receptor 2IIIb (FGFR2IIIb) mRNA was detected in the LE
      and GE of CX uteri. In NOR uteri, c-met was expressed in the LE similar to CX
      uteri, but FGFR2IIIb mRNA levels were lower than in the LE of CX uteri. Uterine
      hepatocyte growth factor (HGF), the ligand for c-met, and FGFR2IIIb mRNA
      expression was substantially lower in NOR ewes, but expression of FGF-7 and FGF
      10 mRNAs, ligands for FGFR2IIIb, was unaffected. These results indicate that NOR
      disrupts endometrial adenogenesis by ablating epithelial ER-alpha expression and
      altering expression of paracrine growth factors and/or receptors involved in
      epitheliomesenchymal interactions. Likewise, these mechanisms are proposed to be
      important regulators of normal uterine gland morphogenesis in the neonate.

PMID- 10954859
TI  - Identification of porcine follipsin as plasma kallikrein, and its possible
      involvement in the production of bradykinin within the follicles of porcine
      ovaries.
AB  - To determine the identity of porcine follipsin, a plasma kallikrein cDNA clone
      was isolated from a porcine liver cDNA library. The clone encoded a protein of
      643 amino acids, exhibiting identities 79.7, 72. 9, and 74.4% homologous to
      human, rat, and mouse plasma prekallikrein, respectively. The amino acid
      sequences of four internal peptides isolated from the tryptic digest of follipsin
      were all found in the deduced sequence. Authentic plasma kallikrein was purified
      from porcine plasma and compared directly with follipsin. Actions on synthetic
      substrates and behaviors with proteinase inhibitors were indistinguishable
      between these two enzymes. The cDNA was expressed in COS-7 cells and the
      recombinant protein was prepared from the culture medium of these cells. No
      active enzyme could be obtained, but the expressed protein was reacted with anti
      porcine plasma kallikrein antibody. The mRNA was detected only in the liver in
      northern blot analysis. RT-PCR analysis of RNAs revealed that porcine testis, in
      addition to the liver, expressed the corresponding mRNA. In the ovary, plasma
      kallikrein was detected as a main band of the active form (Mr = 85,000) and the
      band of the minor inactive precursor form (Mr = 80,000), respectively. In
      contrast, the liver extract contained only the precursor form. Incubation of high
      molecular weight kininogen with follicular fluid plasma kallikrein resulted in an
      increased production of bradykinin. Further, the fresh fluid of large-sized
      follicles of porcine ovaries was found to contain this peptide hormone at a
      detectable level. These results indicate that porcine follipsin is plasma
      kallikrein, and that the enzyme may be involved in the production of bradykinin
      within ovarian follicles.

PMID- 10954860
TI  - Function of the Mos/MAPK pathway during oocyte maturation in the Japanese brown
      frog Rana japonica.
AB  - Fully grown immature oocytes acquire the ability to be fertilized with sperm
      after meiotic maturation, which is finally accomplished by the formation and
      activation of the maturation-promoting factor (MPF). MPF is the complex of Cdc2
      and cyclin B, and its function in promoting metaphase is common among species.
      The Mos/mitogen-activated protein kinase (MAPK) pathway is also commonly
      activated during vertebrate oocyte maturation, but its function seems to be
      different among species. We investigated the function of the Mos/MAPK pathway
      during oocyte maturation of the frog Rana japonica. Although MAPK was activated
      in accordance with MPF activation during oocyte maturation, MPF activation and
      germinal vesicle breakdown (GVBD) was not initiated when the Mos/MAPK pathway was
      activated in immature oocytes by the injection of c-mos mRNA. Inhibition of Mos
      synthesis by c-mos antisense RNA and inactivation of MAPK by CL100 phosphatase
      did not prevent progesterone-induced MPF activation and GVBD. However, continuous
      MAPK activation and MAPK inhibition through oocyte maturation accelerated and
      delayed MPF activation, respectively. Furthermore, Mos induced a low level of
      cyclin B protein synthesis in immature oocytes without the aid of MAPK. These
      results suggest that the general function of the Mos/MAPK pathway, which is not
      essential for MPF activation and GVBD in Rana oocytes, is to enhance cyclin B
      translation by Mos itself and to stabilize cyclin B protein by MAPK during oocyte
      maturation.

PMID- 10954863
TI  - Emerging infectious diseases: a global problem.

PMID- 10954862
TI  - HE2000 AIDS drug shows promise in clinical trials.

PMID- 10954861
TI  - cDNA cloning of bovine midkine and production of the recombinant protein, which
      affects in vitro maturation of bovine oocytes.
AB  - In the present study, we cloned bovine midkine (bMK) cDNA by RT- and RACE-PCR,
      and determined its nucleotide sequence. The nucleotide and deduced amino acid
      sequences of bMK showed a high degree of homology to those of mouse and human MK.
      Moreover, a large amount of recombinant bMK (rbMK) was produced using a
      baculovirus expression system and the protein was purified to homogeneity by
      heparin affinity chromatography. To examine whether treatment with rbMK during in
      vitro maturation (IVM) of bovine cumulus-enclosed oocytes affects their nuclear
      maturation and postfertilization development to the blastocyst stage, bovine
      cumulus-enclosed oocytes obtained from slaughterhouse-derived ovaries were
      cultured for 24 hr in IVM medium without (control) or with various concentrations
      (50-400 ng/ml) of rbMK, followed by in vitro fertilization (IVF) and culture.
      Although rbMK treatment during IVM did not affect the rates of nuclear maturation
      and postfertilization cleavage of oocytes, rbMK at all experimental
      concentrations significantly (P < 0.05) increased the blastocyst yields per
      tested and per cleaved oocyte compared to the control. Next, it was examined
      whether heparitinase (HTN) treatment of cumulus-enclosed oocytes would affect the
      enhancing activity of rbMK during IVM on the developmental competence of oocyte
      after IVF. The enhancing activity of rbMK was completely suppressed by HTN (1.0
      mU/ml) treatment. These results indicate that the presence of rbMK during IVM of
      bovine cumulus-enclosed oocytes can enhance their developmental competence to the
      blastocyst stage after IVF and suggest that heparan sulfate chains on the cell
      surface of cumulus cells and/or oocytes are required for bMK to exert its effect.

PMID- 10954864
TI  - Fibronectin fragment accelerates wound healing in diabetic mice.

PMID- 10954865
TI  - Dissecting the molecular basis of food allergy.

PMID- 10954867
TI  - Rapid update

PMID- 10954866
TI  - A hot summer for islet transplantation.

PMID- 10954868
TI  - PI3-kinase inhibition: a target for drug development?
AB  - The phosphoinositide 3-kinases (PI3-kinases) are a ubiquitously expressed enzyme
      family that, through the generation of phospholipid second messengers, play a key
      role in the regulation of many cellular processes. These include motility,
      proliferation and survival, and carbohydrate metabolism. Members of the PI3
      kinase family and related kinases, their mechanism of activation and the cellular
      events that they influence are described in this review. As knowledge of their
      involvement in disease processes increases, the PI3-kinases appear to be an
      increasingly attractive target for drug development, particularly in the fields
      of cancer and other proliferative diseases, and in the treatment of inflammatory
      and immunological conditions. Evidence of the functional specialization of PI3
      kinase isoforms suggests that selective inhibition with acceptable toxicity might
      be possible.

PMID- 10954869
TI  - Tp53 gene therapy: a key to modulating resistance to anticancer therapies?
AB  - Abnormalities in the p53 tumor suppressor have been identified in over 60% of
      human cancers. The status of p53 within tumor cells has been proposed to be one
      of the major determinants of the response to anticancer therapies. In this review
      we examine the relationship between functional p53 and sensitivity, or
      resistance, to chemotherapy and radiotherapy. We also discuss the potential of
      current gene-therapy approaches to restore functional p53 to tumors as a means of
      modulating the effects of radiation and chemotherapy.

PMID- 10954870
TI  - Viral mechanisms of immune evasion.
AB  - During the millions of years they have coexisted with their hosts, viruses have
      learned how to manipulate host immune control mechanisms. Viral gene functions
      provide an overview of many relevant principles in cell biology and immunology.
      Our knowledge of viral gene functions must be integrated into virus-host
      interaction networks to understand viral pathogenesis, and could lead to new anti
      viral strategies and the ability to exploit viral functions as tools in medicine.

PMID- 10954871
TI  - Cellular and transgenic animal models of cerebrovascular amyloidosis.

PMID- 10954872
TI  - Agony and ecstasy: a review of MDMA effects and toxicity.
AB  - BACKGROUND: Ecstasy is a recreational drug with an anecdotal reputation for
      safety. However, reports of adverse effects and fatalities have increased in the
      medical and popular press. METHOD: Literature search and review. RESULTS: Acute
      Ecstasy toxicity does not appear to be due to overdose and cannot be solely
      attributed to the nature of the usual ambient environment. Adverse effects
      include hyperthermia, seizures, cardiac arrhythmias, hepatotoxicity,
      hyponatraemia and many psychiatric disorders. Ecstasy causes serotonergic
      neurotoxicity in the brains of animals at doses close to those used by humans,
      but its long-term effect on the human brain is unknown. CONCLUSION: Ecstasy
      toxicity should be considered in the differential diagnosis of a variety of
      medical and psychiatric conditions. Given its popularity, both the acute and the
      potential long-term effects are a cause for concern.

PMID- 10954873
TI  - The impact of life events in female patients with fibromyalgia and in female
      healthy controls.
AB  - The aim was to investigate if female fibromyalgia patients (FMS) had experienced
      more negative life events than healthy women. Furthermore, the life events
      experienced in relation to onset of the FMS were evaluated. Another important
      area was to investigate the impact of the events experienced in the patients
      compared to healthy women. A new inventory was constructed to assess life events
      during childhood, adolescence and in adulthood as well as life events experienced
      in relation to the onset of the disorder. Forty female FMS patients and 38
      healthy age-matched women participated in the study. During childhood or
      adolescence 51% of the patients had experienced very negative life events as
      compared to 28% of the controls. Conflict with parents was the most common life
      event. Before onset, 65% of the patients experienced some negative life event.
      Economic problems and conflicts with husband/partner were common. During the last
      year, 51% of the patients had life events which they experienced as very
      negative, compared to 24.5% of the controls (P < 0.01). Stressful life events in
      childhood/adolescence and in adulthood seem to be very common in FMS.
      Furthermore, the life events were experienced as more negative than the life
      events experienced by healthy controls.

PMID- 10954874
TI  - The links between body dysmorphic disorder and eating disorders.
AB  - The aim of the study was to search for a body dysmorphic disorder (BDD) period
      preceding the symptoms meeting the criteria of either anorexia or bulimia
      nervosa, and an evaluation of the prevalence of BDD symptoms in a control group
      of girls without any eating disorder. Ninety-three girls (12-21 years old ) were
      included in the study (36 with anorexia nervosa, 17 with bulimia nervosa and 40
      healthy controls). The Structured Clinical Interview (SCID), including the BDD
      module, and a novel questionnaire (for the presence of preceding life events)
      were used. We found the symptoms of BDD in 25% of anorexia nervosa sufferers for
      at least six months before observing a clear eating disorder picture. Moreover,
      other mental disorders were also present among these patients. The results may
      support the idea that BDD and anorexia nervosa both belong to either OCD or
      affective disorders spectra.

PMID- 10954875
TI  - Polydipsia and water intoxication in 353 psychiatric inpatients: an
      epidemiological and psychopathological study.
AB  - INTRODUCTION: According to several authors, water intoxication can lead to
      irreversible brain damage and could be the cause of nearly a fifth of the deaths
      of schizophrenic patients below the age of 53 years. The aim of our study was
      first to determine the prevalence of polydipsia and water intoxication in a
      population of psychiatric inpatients of a well-defined French geographic area
      (the Somme), and secondly to determine the clinical and socio-demographic factors
      associated with this disorder. METHOD: A cross-sectional survey was done on the
      450 psychiatric beds whose catchment area had a total population of 559,429
      inhabitants. Using staff reports and patients' charts, the drinking habits of 353
      psychiatric inpatients hospitalised during the survey in the 450 psychiatric beds
      of this area were examined. RESULTS: Thirty-eight patients (10.76%; 95%
      confidence interval: 7.53-13.99%) among the 353 inpatients were polydipsic. About
      one-third of these patients were at risk of water intoxication. Polydipsia
      appeared to be significantly associated with male gender, smoking, celibacy and
      chronicity. The polydipsic patients presented also a high prevalence of
      schizophrenia, mental retardation, pervasive developmental disorders and high
      frequency of somatic disorders.

PMID- 10954876
TI  - Two-year outcome in first-episode psychosis treated according to an integrated
      model. Is immediate neuroleptisation always needed?
AB  - In this multicentre study the two-year outcome of two groups of consecutive
      patients (total N = 106) with first-episode functional non-affective psychosis,
      both treated according to the 'need-specific Finnish model', which stresses
      teamwork, patient and family participation and basic psychotherapeutic attitudes,
      was compared. No alternative treatment facilities were available in the study
      sites. The two study groups differed in the use of neuroleptics: three of the
      sites (the experimental group) used a minimal neuroleptic regime whilst the other
      three (the control group) used neuroleptics according to the usual practice.
      Total time spent in hospital, occurrence of psychotic symptoms during the last
      follow-up year, employment, GAS score and the Grip on Life assessment were used
      as outcome measures. In the experimental group 42.9% of the patients did not
      receive neuroleptics at all during the whole two-year period, while the
      corresponding proportion in the control group was 5.9%. The overall outcome of
      the whole group could be seen as rather favourable. The main result was that the
      outcome of the experimental group was equal or even somewhat better than that of
      the control group, also after controlling for age, gender and diagnosis. This
      indicates that an integrated approach, stressing intensive psychosocial measures,
      is recommended in the treatment of acute first-episode psychosis.

PMID- 10954877
TI  - Frequency of neuroleptic malignant syndrome in a large psychiatric hospital in
      Moscow.
AB  - A ten-year prospective survey of neuroleptic malignant syndrome (NMS) was
      performed in a major psychiatric hospital (1,510 beds) in Moscow. All inpatients
      who developed a persistent and severe extrapyramidal rigidity accompanied by
      fever after exposure to neuroleptic medication were screened for NMS. The
      diagnosis of NMS was established according to Levenson's criteria and at a later
      stage all NMS cases were reevaluated using the DSM-IV research criteria. Data on
      age, gender and psychiatric diagnoses were analyzed. Of the 78,708 inpatients
      treated with neuroleptic agents, 19 separate patients had an episode of NMS, for
      a frequency of 0.02%. Mortality rate was 10.5% (2/19 patients). Of the three
      potential risk factors studied, only young age (</= 25 years) was significantly
      associated with an increased frequency of NMS (P < 0. 01). The low rate of NMS
      found here compared to studies in other countries may be due to the stringent
      demands for NMS diagnosis. More large-scale prospective studies including
      detailed clinical and laboratory data are needed to clarify these differences and
      their impact on the prevalence and risk factors of NMS.

PMID- 10954878
TI  - Major symptoms and differential diagnosis of neuroleptic malignant syndrome:
      three case reports.
AB  - The authors describe the cases of three patients presenting a major
      extrapyramidal symptom with rising CPK, inconstant hyperthermia and autonomic
      dysfunction. Through a brief review of the literature, the authors question the
      unity of the malignant syndrome. If hypertonia is quite constant, the rise in the
      seric CPK is aspecific and hyperthermia is inconstant.

PMID- 10954880
TI  - 14F7 Anti-GM3(NeuGc)ganglioside.

PMID- 10954879
TI  - Remission of tardive dyskinesia after changing from flupenthixol to olanzapine.

PMID- 10954882
TI  - MAbM16 Anti-human beta 1 adrenergic receptor.

PMID- 10954881
TI  - 2F12-H9; 2C4-B2; 2C4-A2, anti HBsAg.

PMID- 10954883
TI  - CAb series 1 to 10; GST-ING.

PMID- 10954884
TI  - Identification of diverse HIV type 1 subtypes and dual HIV type 1 infection in
      pregnant Ugandan women.
AB  - Vertical (mother-to-child) transmission accounts for the majority of pediatric
      HIV-1 infections. Many factors are involved in vertical transmission, however it
      is not clear which factors are most important for determining whether a mother
      will transmit HIV-1 to her infant. It has been suggested that HIV-1 subtype may
      influence vertical transmission and that subtype D viruses may be less likely to
      be transmitted in this setting. We analyzed HIV-1 gp120 V3 region sequences from
      the plasma of 20 pregnant Ugandan women of known transmission status who did not
      receive antiretroviral prophylaxis. V3 regions were cloned, sequenced, and
      subtyped by phylogenetic analysis. Among 11 women who transmitted HIV-1 to their
      infants, we detected subtypes A, C, D, and G. Two of the transmitters had dual
      infection with subtypes A and D. In addition, a third was infected with two
      distinct strains of subtype G viruses. HIV-1 subtype A and D viruses were found
      in 9 women who did not transmit the virus to their infants. This study reveals
      that pregnant Ugandan women harbor diverse HIV-1 subtypes, including women who
      transmit HIV-1 to their infants. Transmission of HIV-1 with subtype D V3 regions
      was confirmed in 4 of the 11 transmitters, including 2 who had dual infection
      with subtype A and D HIV-1.

PMID- 10954885
TI  - Factors associated with incident self-reported AIDS among women enrolled in the
      women's interagency HIV study (WIHS). WIHS Collaboratorive Study Group.
AB  - We evaluated factors associated with incident self-reported AIDS diagnoses among
      HIV-infected women in the Women's Interagency HIV Study (WIHS). Baseline
      information included age, race/ethnicity, HIV risk category, site of enrollment,
      years of education, cigarette smoking, CD4 cell count, and HIV viral load.
      Baseline and follow-up data on self-reported AIDS were analyzed using chi-square,
      Kaplan-Meier, and Cox proportional hazard models. Among the 1397 HIV-infected
      women who reported being free of clinical AIDS at baseline, 335 women (24%)
      reported an incident AIDS diagnosis during follow-up. In stratified Kaplan-Meier
      analyses, the development of self-reported AIDS was significantly associated with
      baseline CD4 cell count and viral load (p<0.01). In multivariate Cox proportional
      hazard analyses, women were statistically more likely to report AIDS if they had
      CD4 cell counts below 195 cells/mm3 (p<0.01), HIV RNA >4000 copies/ml (p<0.01),
      were current smokers (p<0.01), and had "no identifiable risk" for acquisition of
      HIV (p = 0.03). Self-reports of a clinical AIDS diagnosis may not always be
      accurate, but laboratory markers of HIV disease indicate that those women who
      self-report such diagnoses have greater immunodeficiency and a higher viral load
      when compared with those who report no AIDS-defining diagnoses.

PMID- 10954886
TI  - Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine,
      nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV
      infected children: week 24 results of a randomized controlled trial--PACTG 377.
      Pediatric AIDS Clinical Trials Group 377 Study Team.
AB  - One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive,
      clinically stable HIV-infected children between 4 months and 17 years of age were
      randomly assigned to receive one of four combination regimens to evaluate the
      change in plasma HIV RNA, safety, and tolerance when changing antiretroviral
      therapy to a protease inhibitor-containing combination regimen. All four regimens
      contained stavudine; in addition children received nevirapine plus ritonavir,
      lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus
      nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine
      plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as
      for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on
      the randomized portion of the study had an HIV RNA response (< or =400 copies/ml)
      on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16.
      At Week 24 the proportion of children with an HIV RNA response still on initial
      therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four
      randomized treatment arms. Rash was frequently seen (27%) on the treatment arms
      containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on
      the bid nelfinavir combination regimen were still on initial therapy with an HIV
      RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid
      nelfinavir combination regimen. A change in antiretroviral therapy to a protease
      inhibitor-containing regimen was associated with a virological response rate of
      approximately 50% for this patient population.

PMID- 10954887
TI  - Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers
      and surrogate end points: a meta-analysis. HIV Surrogate Marker Collaborative
      Group.
AB  - OBJECTIVE: To evaluate treatment-mediated changes in HIV-1 RNA and CD4 count as
      prognostic markers and surrogate end points for disease progression (AIDS/death).
      METHODS: Data from 13,045 subjects in all 16 randomized trials comparing
      nucleoside analogue reverse transcriptase inhibitors and having HIV-1 RNA
      measurements at 24 weeks were obtained. A total of 3146 subjects had HIV-1 RNA
      and CD4 count determinations at 24 weeks after starting treatment. RESULTS: At
      Week 24, the percentage of subjects experiencing an HIV-1 RNA decrease of >1
      log10 copies/ml or a CD4 count increase of >33% was similar (22% vs. 25%).
      Changes in both markers at Week 24 were significant independent predictors of
      AIDS/death: across trials, the average reduction in hazard was 51% per 1 log10
      HIV-1 RNA copies/ml decrease (95% confidence interval: 41%, 59%) and 20% per 33%
      CD4 count increase (17%, 24%). In univariate analyses, the hazard ratio for
      AIDS/death in randomized treatment comparisons was significantly associated with
      differences between treatments in mean area under the curve of HIV-1 RNA changes
      to Weeks 8 and 24 (AUCMB) and mean CD4 change at Week 24, but, in multivariate
      analysis, only mean CD4 change was significant. CONCLUSIONS: Change in HIV-1 RNA,
      particularly using AUCMB, and in CD4 count should be measured to aid patient
      management and evaluation of treatment activity in clinical trials. However,
      short-term changes in these markers are imperfect as surrogate end points for
      long-term clinical outcome because two randomized treatment comparisons may show
      similar differences between treatments in marker changes but not similar
      differences in progression to AIDS/death.

PMID- 10954888
TI  - Residual HIV-RNA levels persist for up to 2.5 years in peripheral blood
      mononuclear cells of patients on potent antiretroviral therapy.
AB  - The long-term response of 10 asymptomatic, antiretroviral therapy-naive HIV-1
      infected patients to potent combination antiretroviral therapy was characterized
      by monitoring levels of HIV-1 RNA in plasma, peripheral blood mononuclear cells
      (PBMC), and lymphoid tissue using highly sensitive HIV-1 RNA assays. Although
      plasma viral loads were continuously suppressed to levels below 50 HIV-1 RNA
      copies/ml for up to 2.5 years (60-128 weeks), HIV-1 RNA was still detectable at
      very low levels (1 to 49 HIV-1 RNA copies/ml) in 25% of the samples. In
      corresponding PBMC specimens, residual HIV-RNA was detectable in as much as 91%
      of samples tested (1 to 420 HIV-1 RNA copies/microg total RNA). Similarly, HIV-1
      RNA levels in lymphoid tissue also remained detectable at a high frequency (86%).
      A highly significant correlation was demonstrated between therapy-induced change
      in PBMC HIV-1 RNA levels and change in plasma HIV-1 RNA levels (r2 = 0.69; p =
      0.003). These findings support the concept that measurement of HIV-1 RNA in the
      easily accessible PBMC compartment is relevant for evaluating the potency of
      current and future antiretroviral therapies.

PMID- 10954890
TI  - HIV type 1 protease cleavage site mutations and viral fitness: implications for
      drug susceptibility phenotyping assays.
AB  - The recombinant virus assay (RVA) is a method for assessing the susceptibility of
      human immunodeficiency virus type 1 (HIV-1) plasma isolates to antiretroviral
      drugs. The RVA involves the production of viable virus in vitro by homologous
      recombination of RT-PCR products from plasma virus with a noninfectious reverse
      transcriptase (RT) or protease (PR)-deleted cloned HIV-1 provirus. In this study,
      we have constructed RVA plasmids with contiguous deletions in RT, PR, and the
      p7/p1 and p1/6 gag protease cleavage sites (CS). The deletions in these plasmids
      allow generation of recombinant viruses with all loci currently identified as
      important for resistance to anti-HIV-1 drugs being derived from the clinical
      isolate, including CS mutations that compensate for the reduced fitness of
      viruses resistant to protease inhibitors (Doyon et al., J Virol 1996:70:3763
      3769). We have also used these new constructs to generate viruses with or without
      compensatory CS mutations, and examined the effects on fitness. In the case of an
      indinavir-selected virus, fitness was restored close to that of a wild type virus
      when a vector deleted in the CS and PR was used. With an amprenavir-selected
      isolate, virus fitness was incompletely restored by including the CS, and this
      defect appeared to be partially due to reduced infectivity of the virions. We
      conclude that the CS mutations were required for optimum detection of resistance
      in the RVA, but that virus fitness can remain compromised even in the presence of
      compensatory CS mutations.

PMID- 10954889
TI  - Identification of the glycoprotein 41(TM) cytoplasmic tail domains of human
      immunodeficiency virus type 1 that interact with Pr55Gag particles.
AB  - We investigated the protein/protein interactions that occur during human
      immunodeficiency virus (HIV-1) budding. We evaluated the binding to Pr55Gag
      particles of peptides mapping to the cytoplasmic tail of gp41TM and of host-cell
      proteins, in a cell-free, in vitro assay. Host-cell proteins and irrelevant viral
      envelope peptides did not bind. Peptides corresponding to a large central domain
      of the gp41TM cytoplasmic tail (93 residues) bound to Pr55Gag particles. This
      demonstrates that a Gag/Env interaction is responsible for the specific
      incorporation of the Env glycoprotein into nascent HIV-1 virions, and defines
      more accurately the gp41TM domain involved in this interaction.

PMID- 10954891
TI  - Isolation of cytomegalovirus-specific cytotoxic T-lymphocytes from gut-associated
      lymphoid tissue (GALT) of HIV type 1-infected subjects.
AB  - Cytomegalovirus (CMV) can be an important opportunistic infection in HIV-1
      infected patients, particularly when the CD4+ T-cell count drops below 50
      lymphocytes/mm3. CMV-associated disease, including retinitis, pneumonitis,
      gastroenteritis, and encephalitis, is estimated to affect up to 40% of AIDS
      patients. We have studied the cellular immune response to CMV in gut-associated
      lymphoid tissue (GALT) of HIV-1-infected patients. Two patients with chronic
      diarrhea of unknown etiology were examined by flexible sigmoidoscopy and upper
      endoscopy. Biopsy specimens were obtained from lymphoid-associated tissue sites
      in rectum and duodenum. Both patients were seropositive for CMV IgG, but had not
      been treated with ganciclovir, and neither had clinical signs of CMV disease.
      Mononuclear cell cultures were established from GALT and blood and assayed for
      the presence of CMV-specific CD8+ T cells. CD8+ T-cell phenotype and function
      were assessed by MHC Class I tetramer staining, using an HLA-A*0201 tetramer
      complex specific for peptide 495-503 (NLVPMVATV) of CMV lower matrix protein
      pp65, and by a standard 51Cr release assay. CMV pp65-specific cytotoxic
      lymphocytes (CTL) were detected in GALT and blood MNC from both patients. These
      results demonstrate that HIV-1-infected subjects seropositive for CMV, but
      without active CMV gastrointestinal disease, harbor CMV-specific CTL in
      intestinal lymphoid tissue. This is the first report of isolation of CMV-specific
      CTL in GALT and will lead to greater understanding of the pathogenesis of CMV
      disease in human mucosal tissue.

PMID- 10954892
TI  - Sensory evoked potentials in SIV-infected monkeys with rapidly and slowly
      progressing disease.
AB  - Human immunodeficiency virus (HIV-1) infects the central nervous system (CNS)
      early in the course of disease progression and leads to some form of neurological
      disease in 40-60% of cases. Both symptomatic and asymptomatic HIV-infected
      subjects also show abnormalities in evoked potentials. As part of an effort to
      further validate an animal model of the neurological disease associated with
      lentiviral infection, we recorded multimodal sensory evoked potentials (EPs) from
      nine rhesus macaques infected with passaged strains of SIVmac (R71/E17), prior to
      and at 1 month intervals following inoculation. The latencies of forelimb and
      hindlimb somatosensory evoked potentials (SEP) and flash visual evoked potentials
      (VEP) were measured. Within 14 weeks of inoculation, all but two animals had
      progressed to end-stage disease (rapid progressors). The two animals with slowly
      progressing disease (AQ15 and AQ94) had postinoculation life spans of 109 and 87
      weeks, respectively. No significant changes were observed in evoked potentials
      recorded during the control period or at any time in the animals with slowly
      progressing disease. However, all of the monkeys with rapidly progressing disease
      exhibited increases in latency for at least one evoked potential type. The
      overall mean increases in somatosensory and visual evoked potential peak
      latencies for the rapid progressors were 22.4 and 25.3%, respectively. For
      comparison, the changes in slow progressors were not significant (1.8 and -1.9%,
      respectively). These results, coupled with our previous finding of slowed motor
      evoked potentials in the same cohort of macaques (Raymond et al.: J Neurovirol
      1999;5:217-231), demonstrate a broad and somewhat variable pattern of viral
      injury to both sensory and motor system structures, resembling the findings in
      HIV-infected humans. These results coupled with our earlier work demonstrating
      cognitive and motor behavioral impairments in the same monkeys support the use of
      the SIVmac-infected rhesus macaque as a model of AIDS-related neurological
      disease.

PMID- 10954893
TI  - Construction and biological characterization of an infectious molecular clone of
      HIV type 1GB8.
AB  - Here we report the construction, sequencing, and repair of a molecular clone of
      HIV-1GB8, a virus representative of HIV-1 subtype B strains circulating in the
      UK. The phenotype of virus produced by the clone matches that of the parental
      virus. The molecular clone will be used in the production of attenuated virus
      stocks for chemical inactivation to allow development of faccines based on killed
      whole virus preparations.

PMID- 10954894
TI  - CXCR4 homologues of gibbon ape, African green monkey, squirrel monkey, and cotton
      top marmoset.
AB  - CXCR4 gene homologues were isolated from an ape (gibbon), an Old World monkey
      (African green monkey), and two New World monkeys (squirrel monkey and cotton-top
      marmoset), and their DNA sequences determined. The squirrel monkey and cotton-top
      marmoset CXCR4 sequences more closely resemble homologues from apes than Old
      World monkeys, a pattern not seen for the related chemokine receptor CCR5. The
      African green monkey CXCR4 gene is similar to its homologue in baboon, a pattern
      that has also been seen among CCR5 homologues. The gibbon CXCR4 contains the
      first polymorphisms recognized in ape homologues, the human and chimpanzee CXCR4
      proteins being identical, and two of these three differences are also observed in
      one or more Old World monkey homologues. While 18 positions within CXCR4 are now
      known to be polymorphic in primates, 7 of these polymorphisms have been observed
      in multiple examples and 11 have been observed only once.

PMID- 10954895
TI  - Near full-length genome analysis of HIV type 1 CRF02.AG subtype C and CRF02.AG
      subtype G recombinants.
AB  - HIV-1 CRF02.AG strains are prevalent in west and west-central Africa, suggesting
      a longstanding presence of these subtype A/G recombinants in the global epidemic.
      Cocirculation of CRF02.AG strains with other group M subtypes may give rise to
      HIV-1 recombinants constituting a mosaic genome comprising fragments of three
      different subtypes. We report on the genetic analysis of the near-full-length
      genomes of such recombinants (VI1035 and VI1197) as well as CRF02.AG strains in
      Belgian individuals. VI1035 and VI1197 may be the result of successful "second
      generation" recombinations of HIV-1 strains CRF02.AG with, respectively, subtype
      C (VI1035) and G (VI1197) strains in a dually infected individual.

PMID- 10954896
TI  - Evidence of subtype B-like sequences in the V3 loop region of human
      immunodeficiency virus type 1 in Kilimanjaro, Tanzania.
AB  - The aim of this study was to determine the nucleotide sequence of the third
      variable (V3) domain of HIV-1 gp120 from strains circulating in the Kilimanjaro
      region of Tanzania. DNA from this region was amplified from patient peripheral
      blood lymphocytes using polymerase chain reaction and then subjected to automated
      DNA sequencing. Subtype A, B, C, and D-like sequences were identified. Subtype B
      has not previously been described in Tanzania.

PMID- 10954898
TI  - Gene transfer of endothelial nitric oxide isoform decreases rat hindlimb vascular
      resistance in vivo.
AB  - The objective of this study was to design a methodology of gene transfer into a
      resistance vascular bed and to show if such a method can be used to examine the
      physiological function of a given gene product in vivo. We developed such a
      method and validated it by defining the role in vivo of endothelial nitric oxide
      synthase (eNOS). In a constant flow perfused rat hindlimb, gene transfer to the
      vascular endothelium was accomplished by incubating a "first-generation" serotype
      5, replication-deficient, adenoviral vector (1.2 X 10(9) plaque-forming units/ml)
      containing cDNA encoding either the eNOS or the beta-galactosidase (beta-Gal)
      gene in the hindlimb vasculature for 30 min. Five days after infection,
      immunohistochemical staining for eNOS localized recombinant gene expression to
      vascular endothelial cells and eNOS protein levels were increased fourfold (11.9
      +/- 6.6 vs. 2.9 +/- 1.3 intensity units/microg protein, n = 4, p < 0.05).
      Perfusion pressures were measured at different flow rates (10-50 ml/min). In
      addition, basal and acetylcholine (ACh)-stimulated vascular resistance (VR) in
      phenylephrine (PE)-precontracted (100 microM) hindlimb was measured at constant
      flow. There were flow-dependent increases (p < 0.05) in perfusion pressure.
      Overexpression of eNOS shifted the pressure-flow curve downward and
      administration of N(G)-nitro-L-arginine methyl ester (L-NAME) shifted the curve
      upward. Compared with beta-Gal-transfected rats, PE-induced VR decreased (p <
      0.05) in eNOS-transfected rats (100 +/- 27 vs. 164 +/- 49 mmHg, n = 5). Addition
      of 100 microM L-NAME increased (p < 0.05) PE-induced VR in both eNOS-transfected
      and control rats (145 +/- 50 and 232 +/- 38 mmHg, n = 5, p < 0.05), respectively,
      which was partially abolished by L-arginine pretreatment. ACh-induced
      vasorelaxation was increased 45% (p < 0.05) in eNOS-transfected hindlimbs. L-NAME
      decreased (p < 0.05) ACh-induced vasorelaxation by 58% in eNOS-transfected
      hindlimbs versus 25% in beta-Gal-transfected hindlimbs (p < 0.05). We used this
      gene transfer method to examine the physiological function of a gene product in
      vivo and showed that (1) the flow-pressure relationship in the hindlimb vascular
      bed is NO dependent and (2) the eNOS enzyme modulates NO-mediated vasorelaxation
      in the rat hindlimb resistance arteries in vivo.

PMID- 10954897
TI  - Expression of wild-type and noncleavable Fas ligand by tetracycline-regulated
      adenoviral vectors to limit intimal hyperplasia in vascular lesions.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) and the infiltration of T
      cells and macrophages into vessel wall are considered to be important for intimal
      lesion formation after balloon angioplasty. Previous studies have shown that Fas
      ligand (FasL) gene transfer to balloon-injured vessels inhibits lesion formation
      by killing both proliferating VSMCs and infiltrating inflammatory cells. Here, we
      describe the construction and utility of a binary, tetracycline-regulated
      adenovirus system that provides controlled transgene expression in vitro and in
      vivo. In this system, optimal transgene expression required cotransfection with
      an adenovirus encoding the tetracycline-dependent trans-activator (rtTA) and
      induction with doxycycline hydrochloride (DOX), an analog of tetracycline. Using
      this system, adenovirus constructs were designed that allow regulated expression
      of wild-type FasL and a noncleavable mutant of FasL (FasL-NC). Transduction of
      FasL and FasL-NC induced similar extents of apoptosis in proliferating VSMCs in
      vitro in a manner that was dependent on the doses of the rtTA adenovirus and the
      presence of DOX in the medium. Furthermore, inhibition of intimal hyperplasia in
      injured carotid arteries by FasL or FasL-NC transduction was also dependent on
      cotransfection with the rtTA adenovirus and administration of DOX by subcutaneous
      injection. In contrast to wild-type FasL, transduction of FasL-NC did not result
      in the production of soluble (cleaved) FasL in the medium of infected cells in
      vitro, or in the serum of rats after local gene transfer to carotid arteries. In
      conclusion, this binary tetracycline-inducible adenovirus system may allow for
      safer delivery of cytotoxic genes for therapeutic purposes.

PMID- 10954899
TI  - Biolistic-mediated interleukin 4 gene transfer prevents the onset of type 1
      diabetes.
AB  - We tested the efficacy of biolistic-mediated gene transfer as a noninvasive
      therapy for type 1 diabetes (T1D) in nonobese diabetic (NOD) mice by expression
      of murine interleukin 4 (mIL-4) cDNA. Epidermal delivery of 2 microg of DNA
      yielded transient detection of serum mIL-4, using a conventional cDNA expression
      vector. A vector stabilized by incorporation of the Epstein-Barr virus (EBV)
      EBNA1/oriP episomal maintenance replicon produced higher levels of serum mIL-4
      that persisted for 12 days after inoculation. Although biolistic inoculation of
      either vector reduced insulitis and prevented diabetes, the protracted mIL-4
      expression afforded by the EBV vector resulted in Th2-type responses in the
      periphery and pancreas and more significant protection from the onset of
      diabetes. Our studies demonstrate the efficacy of biolistic gene delivery of
      stabilized cytokine expression as a viable therapeutic approach to prevent the
      onset of T1D.

PMID- 10954900
TI  - Using a tropism-modified adenoviral vector to circumvent inhibitory factors in
      ascites fluid.
AB  - Peritoneal compartmentalization of advanced stage ovarian cancer provides a
      rational scenario for gene therapy strategies. Several groups are exploring
      intraperitoneal administration of adenoviral (Ad) vectors for this purpose. We
      examined in vitro gene transfer in the presence of ascites fluid from ovarian
      cancer patients and observed significant inhibition of Ad-mediated gene transfer.
      The inhibitory activity was not identified as either complement or cellular
      factors, but depletion of IgG from ascites removed the inhibitory activity,
      implicating neutralizing anti-Ad antibodies. A wide range of preexisting anti-Ad
      antibody titers in patient ascites fluid was measured by ELISA. Western blot
      analysis demonstrated that the antibodies were directed primarily against the Ad
      fiber protein. To circumvent inhibition by neutralizing antibodies, a genetically
      modified adenoviral vector was tested. The Ad5Luc.RGD vector has an Arg-Gly-Asp
      (RGD) peptide sequence inserted into the fiber knob domain and enters cells
      through a nonnative pathway. Compared with the conventional Ad5 vector,
      Ad5Luc.RGD directed efficient gene transfer to cell lines and primary ovarian
      cancer cells in the presence of ascites fluid containing high-titer neutralizing
      anti-Ad antibodies. These results suggest that such modified Ad vectors will be
      needed to achieve efficient gene transfer in the clinical setting.

PMID- 10954901
TI  - GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes
      the bone marrow toxicity of cyclophosphamide in mice.
AB  - Autologous transplantation of bone marrow cells (BMCs) transduced with the
      multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has
      already been applied in clinical chemoprotection trials. However, anticancer
      drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents,
      are not relevant to MDR1 or DHFR gene products. In this context, we have
      previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced
      human CD34(+) cells showed resistance in vitro against 4
      hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the
      present study, a subsequent attempt was made in a murine model to evaluate the
      effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow
      against high-dose CY. The gene transfection was carried out retrovirally,
      employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM
      was 30%. After the transplantation, recipient mice (GST-pi mice) received three
      sequential courses of high-dose CY. As the chemotherapy courses advanced, both
      shortening of recovery period from WBC nadir and shallowing of WBC nadir were
      observed. In contrast to the fact that three of seven control mice died, possibly
      due to chemotoxicity, all seven GST-pi mice were alive after the third course, at
      which point the vector GST-pi gene was detected in 50% of CFU-GM derived from
      their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these
      seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from
      BMCs showed positive signals for vector GST-pi DNA after 6 months. These data
      indicate that the GST-pi gene can confer resistance to bone marrow against CY by
      being transduced into long-term repopulating cells.

PMID- 10954902
TI  - Intravesical and intravenous therapy of human bladder cancer by the herpes vector
      G207.
AB  - G207, a conditionally replicating herpes vector, efficiently kills human bladder
      cancer cells in vitro. To evaluate the therapeutic potential of G207, we have
      established three in vivo models similar to the clinical situation. In vivo, G207
      was intraneoplastically, intravesically, or intravenously inoculated in nude
      mice. Intraneoplastic inoculation into subcutaneous tumor caused significant
      tumor growth inhibition. Intravesical inoculation of G207 also caused decreased
      tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple
      intravenous inoculation markedly inhibited subcutaneous tumor growth. These
      results suggest that intravesical therapy with G207 is effective for localized
      bladder tumor, especially for carcinoma in situ (CIS), and intravenous therapy
      with G207 is promising for invasive or metastasized bladder tumor.

PMID- 10954903
TI  - Inhibition of human immunodeficiency virus transmission to CD4+ T cells after
      gene transfer of constitutively expressed interferon beta to dendritic cells.
AB  - CD34(+)-derived dendritic cells (DCs) can be infected by the T cell-tropic HIVLAI
      strain, but are poorly permissive for efficient virus production. However, HIVLAI
      infected DCs are able to transmit a vigorous cytopathic infection to activated
      CD4(+) T cells. We show that DCs differentiated from CD34(+) cells can be
      efficiently transduced by a retroviral vector carrying the IFN-beta coding
      sequence. This results in resistance to infection by HIV as shown by a threefold
      reduction in the HIV DNA copy number per cell, and by inhibition of HIV
      transmission from DCs to CD4(+) T cells. Moreover, constitutive IFN-beta
      production by DCs increases the synthesis of IL-12 and IFN-gamma Th1-type
      cytokines and of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES. This
      indicates that IFN-beta transduction of DCs blocks HIV infection and viral
      transmission to CD4(+) T cells, and could favor cellular immune responses in HIV
      infected patients.

PMID- 10954904
TI  - Direct exposure of mouse spermatogenic cells to high doses of adenovirus gene
      therapy vector does not result in germ cell transduction.
AB  - The potential for adenovirus gene therapy vectors to gain access to male germ
      cells was rigorously tested in the mouse by injecting high titers of the vector
      directly into the testis and epididymis, or by exposing sperm to the vector
      immediately prior to or during in vitro fertilization. The adenovirus vector
      carried the bacterial lacZ gene (Adbeta-Gal) driven by the Rous sarcoma virus
      (RSV) promoter, and infection was assessed by testing for lacZ expression, either
      with antibodies to LacZ protein or by staining for LacZ enzymatic activity. A
      total of 109 plaque-forming units (PFU) was inserted into the testis or
      epididymis, and in vitro fertilization was performed after sperm were exposed
      either to 10 or 100 PFU per sperm cell. lacZ expression was examined within
      testes for several weeks after injection, and in preimplantation embryos produced
      by in vitro fertilization with sperm exposed to the gene therapy vector. Direct
      injection of Adbeta-Gal into either the testis or epididymis resulted in lacZ
      expression only within the interstitium of the testis and not within seminiferous
      tubules. Despite direct exposure of spermatogenic cells or mature sperm to high
      titers of virus, lacZ expression was likewise not detected in embryos. These
      findings are consistent with the conclusion that the risk is minimal for germ
      line integration of adenovirus vectors exposed to male reproductive cells.

PMID- 10954905
TI  - Development of a rapid method for the PEGylation of adenoviruses with enhanced
      transduction and improved stability under harsh storage conditions.
AB  - PEGylation is the covalent attachment of activated monomethoxy poly(ethylene)
      glycols (MPEGs) to free lysine groups of therapeutic proteins. This technology
      has enhanced the physical stability of proteins and ablated humoral immune
      responses generated against them. In this study, adenoviral vectors were modified
      with MPEGs activated by cyanuric chloride, succinimidyl succinate, and tresyl
      chloride. Under proper buffering conditions, reactions were complete within 2 hr.
      Transduction efficiency of PEGylated adenoviruses was not compromised by
      neutralizing antibodies to native adenovirus in vitro. These preparations
      retained titers that were significantly greater than those of the unconjugated
      virus after storage at 42, 25, 4, and -20 degrees C. Stability profiles of
      PEGylated preparations at -20 degrees C suggest that glycerol could be eliminated
      from formulations without significant loss of viral titer. PEGylated adenoviruses
      produced a two- to threefold increase in transduction in the lung when
      administered by intratracheal injection and a fivefold increase in transduction
      in the liver when administered intravenously.

PMID- 10954906
TI  - Neuroprotective gene therapy for Huntington's disease using a polymer
      encapsulated BHK cell line engineered to secrete human CNTF.
AB  - Huntington's disease (HD) is an autosomal dominant genetic disease with
      devastating clinical effects on cognitive, psychological, and motor functions.
      These clinical symptoms primarily relate to the progressive loss of medium-spiny
      GABA-ergic neurons of the striatum. There is no known treatment to date. Several
      neurotrophic factors have, however, demonstrated the capacity to protect striatal
      neurons in various experimental models of HD. This includes the ciliary
      neurotrophic factor (CNTF), the substance examined in this protocol. An ex vivo
      gene therapy approach based on encapsulated genetically modified BHK cells will
      be used for the continuous and long-term intracerebral delivery of CNTF. A
      device, containing up to 106 human CNTF-producing BHK cells surrounded by a
      semipermeable membrane, will be implanted into the right lateral ventricle of 6
      patients. Capsules releasing 0.15-0.5 microg CNTF/day will be used. In this phase
      I study, the principal goal will be the evaluation of the safety and tolerability
      of the procedure. As a secondary goal, HD symptoms will be analyzed using a large
      battery of neuropsychological, motor, neurological, and neurophysiological tests
      and the striatal pathology monitored using MRI and PET-scan imaging. It is
      expected that the gene therapy approach described in this protocol will mitigate
      the side effects associated with the peripheral administration of recombinant
      hCNTF and allow a well-tolerated, continuous intracerebroventricular delivery of
      the neuroprotective factor.

PMID- 10954908
TI  - Future meetings of the NIH recombinant DNA advisory committee (RAC) and gene
      therapy policy conferences (GTPC)

PMID- 10954909
TI  - Human gene marker/therapy clinical protocols (complete updated listings).

PMID- 10954907
TI  - Transfer of interleukin-4 and interleukin-10 in patients with severe inflammatory
      bowel disease of the rectum.
AB  - Inflammatory bowel disease (IBD) comprises the two disorders ulcerative colitis
      (UC) and Crohn's disease (CD). Although the etiology is still unclear, initiation
      and aggravation of the inflammatory processes seem to be due to a massive local
      mucosal immune response. An increased number of greatly activated macrophages
      seems to contribute to the onset of IBD by expressing upregulated costimulatory
      molecules (e.g., CD80/CD86) and a cytokine profile favouring a type I
      proinflammatory response. The release of interleukin 2 (IL-2) and Interferon
      gamma (IFN-gamma) by naive T lymphocytes predominantly stimulates cytotoxic T
      lymphocytes, macrophages, and natural killer (NK) cells and increases the antigen
      presenting potential of all these cell types. Opposite this proinflammatory
      immune reaction a compensatory type II antiinflammatory response has been
      suggested in the inflamed mucosa, involving mainly interleukin 4 and interleukin
      10. Both cytokines are able to down-regulate inflammatory mediators including
      tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 and favor a humoral
      immune response. The main goal of this clinical trial is the local liposome
      mediated gene transfer of these two antiinflammatory cytokines, interleukin 4 and
      interleukin 10, in patients with severe IBD of the rectum. This local
      administration of antiinflammatory cytokines will avoid toxic systemic side
      effects, prevents blocking of the beneficial effects of proinflammatory
      cytokines, e.g., TNF-alpha in other tissue compartments and increases the local
      concentration of interleukin 4 and interleukin 10 over a prolonged period of
      time. The combined effects of IL-4 and IL-10 have been shown to shift the Th1/Th2
      cell activation in favor of a Th2 immune response which seems to be essential for
      fighting against the inflammation and ultimative healing.

PMID- 10954910
TI  - Antiviral and antiluteolytic activity of recombinant bovine IFN-omega1 obtained
      from Pichia pastoris.
AB  - The gene coding for bovine interferon-omega1 (BoIFN-omega1) was recently cloned
      and expressed at high levels in the yeast Pichia pastoris. The recombinant BoIFN
      omega1 protein shows antiviral activity in different cell lines and has an
      antiluteolytic effect in cyclic ewes. In this article, we describe a method for
      purification of BoIFN-omega1 expressed in the methylotrophic yeast P. pastoris
      and characterization of its activity in vivo. The recombinant protein secreted to
      the culture medium had low activity because of self-aggregation. BoIFN-omega1 was
      solubilized using urea and desalting and finally purified by ion exchange
      chromatography on Q-Sepharose Fast Flow. The yield of purified product was
      approximately 300 mg/L of fermentation culture, with a specific antiviral
      activity of 10(8) IU/mg. Its purity was at least 80%. The biologic
      characterization of purified BoIFN-omega1 was determined by induction of an
      antiviral state on ewes challenged with 100 lethal doses (LD) of Aujeszky virus
      and by the extension of the corpus luteum life span and interestrous interval in
      cyclic cows. Ewes treated with 2 x 106 IU/kg BoIFN-omega1 were protected from
      Aujeszky virus infection. In cows receiving an intrauterine infusion of 1 mg
      BoIFN-omega1, equally distributed between the two uterine horns, twice daily from
      day 14 to day 22 of the experimental estrous cycle, the lifespan of the corpus
      luteum (25 vs. 19 days) and the interestrous intervals (26 vs. 21 days) were
      extended when compared with a control group (p < 0.05). We show that recombinant
      BoIFN-omega1 purified from P. pastoris has high antiviral activity and is an
      effective antiluteolytic agent in cattle.

PMID- 10954912
TI  - Crystal structure of recombinant native SDF-1alpha with additional mutagenesis
      studies: an attempt at a more comprehensive interpretation of accumulated
      structure-activity relationship data.
AB  - Crystal structures, forms 1 and 2, of recombinant native stromal cell-derived
      factor-1alpha (SDF-1alpha), expressed using the Sendai virus expression vector
      system, have been determined by x-ray crystallography at 2.0 A resolution. The
      crystal of form 1 is almost isomorphous with that used in the previous crystal
      structure analysis of the synthetic [N33A] mutant of SDF-1alpha (Dealwis, C., et
      al. Proc. Natl. Acad. Sci. USA 1998;95, 6941-6946). However, the present
      structure analysis led to considerably better refinement statistics, revealing an
      error in the structural assignment of N-terminal residues in the previous report.
      Comparison of the solution structure, as previously determined by nuclear
      magnetic resonance (NMR) spectroscopy, and the present structure, with two
      monomers in the asymmetric unit, reveals several local conformational
      differences. Alanine scan mutagenesis studies for each residue in the so-called
      RFFESH motif revealed that only the first residue, Arg12, is effective in
      enhancing receptor binding (and successive activation). A new notion that steric
      restraint between Arg8 and Arg12 is favorable (if not vital) for retaining SDF
      activities appears to explain more consistently the structure-activity
      relationship data accumulated to date. Four guiding principles are presented that
      may be useful for designing potent therapeutic compounds interfering with HIV-1
      infection through competition at the CXCR4 coreceptor.

PMID- 10954911
TI  - Combined treatment with low-dose interferon plus vinblastine is associated with
      less toxicity than conventional interferon monotherapy in patients with
      metastatic renal cell carcinoma.
AB  - The outcome of treatment of advanced renal cell carcinoma is disappointing. In
      interferon (IFN)-treated patients, the high incidence of adverse effects causes
      many patients to withdraw from treatment. This 12-week randomized study compared
      the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U
      thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U
      thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive
      patients. There was no significant difference in response rate between treatment
      arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location).
      Combined treatment was associated with a significantly lower incidence of fever,
      fatigue, and weight loss but with a higher incidence of leukopenia. There was no
      significant difference in the incidence of other events. More patients treated
      with IFN monotherapy required bed rest, and overall treatment costs were 60%
      higher than for combined treatment. It is concluded that combined treatment with
      low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated
      and less expensive than high-dose IFN monotherapy.

PMID- 10954913
TI  - Cloning of an Mx cDNA from Atlantic halibut (Hippoglossus hippoglossus) and
      characterization of Mx mRNA expression in response to double-stranded RNA or
      infectious pancreatic necrosis virus.
AB  - Mx proteins are GTPases that are specifically induced by type I interferons (IFN)
      in vertebrates. Some mammalian Mx proteins have antiviral activity against
      certain RNA viruses. A 2.3-kb full-length cDNA clone of an Atlantic halibut Mx
      gene was isolated from a liver cDNA library. The open reading frame (ORF)
      predicts a 622 amino acid protein of 71.2 kDa possessing a tripartite GTP binding
      motif, a dynamin signature, and a leucine zipper motif, which are conserved in
      all known Mx proteins. The C-terminal half contains a putative bipartite nuclear
      localization signal. The deduced halibut Mx protein showed approximately 76%
      sequence identity with the Atlantic salmon and rainbow trout Mx proteins, 55%
      identity with the human MxA, and 48% identity with the chicken Mx protein. Based
      on sequence comparison of 554-bp Mx cDNA fragments, the Atlantic halibut Mx
      showed more relationship with the perch and turbot than the salmonid Mx genes.
      Halibut appears to possess at least two Mx loci, as suggested by Southern blot
      analysis of genomic DNA. Two halibut Mx transcripts (2.2 kb and 2.6 kb) were
      strongly induced in vivo by the double-stranded RNA (dsRNA) poly I:C or
      infectious pancreatic necrosis virus (IPNV) in all organs studied.

PMID- 10954914
TI  - Sequence comparison of avian interferon regulatory factors and identification of
      the avian CEC-32 cell as a quail cell line.
AB  - Interferon (IFN) regulatory factor-1 (IRF-1) is a well-characterized member of
      the IRF family. Previously, we have cloned cDNA of several members of the chicken
      IRF (ChIRF) family and studied the function of ChIRF-1 in the avian cell line CEC
      32. The IRF-1 proteins from primary chicken embryo fibroblasts (CEF) and CEC-32
      cells differed in their electrophoretic mobility. To characterize the different
      forms of IRF-1 in avian cells, we compared the sequences of IRF-1 cDNA from CEC
      32 cells, primary CEF, and quail fibroblasts (QEF). The deduced amino acid
      sequences of IRF-1 cDNA from chicken and quail show high similarity. Comparison
      of genomic sequences of IRF-1 and IFN consensus sequence binding protein (ICSBP)
      also confirm the relatedness of the members of the IRF family in quail and
      chicken. Based on these data, it is concluded that the avian fibroblast cell line
      CEC-32 is derived from quail. This conclusion is further supported by
      deoxynucleotide sequence comparison of a DNA fragment in an avian MHC class II
      gene and by fluorescence in situ hybridization (FISH) using the vertebrate
      telomeric (TTAGGG) repeat. Chromosome morphology and the lack of interstitial
      hybridization signals in macrochromosomes suggest that the CEC-32 cell line has
      probably been derived from Japanese quail.

PMID- 10954915
TI  - The impact of the ovulatory cycle on cytokine production: evaluation of systemic,
      cervicovaginal, and salivary compartments.
AB  - To understand the impact of the menstrual cycle on immunologic parameters, we
      measured the level of cytokines and chemokines from plasma, cervicovaginal lavage
      (CVL), and saliva samples of 6 premenopausal women during the follicular and
      luteal phases of the ovulatory cycle. We demonstrate that the level of plasma
      interleukin-8 (IL-8) was 4-fold higher during the follicular phase than the
      luteal phase (p = 0.004), whereas plasma IL-1beta, IL-4, IL-6, IL-10, interferon
      gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), tumor necrosis
      factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha),
      and TNF receptor II (TNFR II) were not altered during the ovulatory cycle. In the
      vaginal compartment, as measured from CVL samples, the levels of IL-6 and IL
      1beta were both 5-fold higher in the follicular than the luteal phase (p = 0.0002
      and 0.03, respectively). Salivary cytokine and chemokine samples were similar
      when measured during the luteal and the follicular phases. Additional analysis of
      lymphocyte subsets for phenotypic and functional markers indicated that they were
      not influenced by the ovulatory cycle. Collectively, these data suggest that IL
      6, IL-8, and IL-1beta are differentially regulated during the ovulatory cycle.

PMID- 10954916
TI  - Bcl-x(L) suppresses TNF-mediated apoptosis and activation of nuclear factor
      kappaB, activation protein-1, and c-Jun N-terminal kinase.
AB  - Tumor necrosis factor (TNF) is a multipotential cytokine that induces apoptosis
      and activates nuclear factor-kappa B (NF-kappaB), activation protein 1 (AP-1),
      mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK).
      Several mechanisms have been suggested to explain these effects of TNF, one of
      them being the involvement of reactive oxygen intermediates (ROI). Because Bcl-2
      family members are known to affect the redox status of the cell, we examined the
      effect of Bcl-x(L) expression on TNF signaling. Overexpression of Bcl-x(L) in
      human promyelocytic lymphoma HL-60 cells downregulated TNF-induced cytotoxicity.
      Cleavage of poly (ADP-ribose) polymerase by caspases, an early indicator of
      apoptosis, was also blocked by Bcl-x(L) overexpression. Activation of NF-kappaB
      was significantly suppressed in cells overexpressing Bcl-x(L), as was degradation
      of IkappaBalpha, the inhibitory subunit of NF-kappaB. NF-kappaB activation
      induced by serum-activated lipopolysaccharide (SALPS), ceramide, and okadaic acid
      was also inhibited by overexpression of Bcl-x(L), whereas that by phorbol
      myristate acetate (PMA) and H2O2 was unaffected. Besides NF-kappaB, the
      activation of AP-1 by TNF also was blocked by Bcl-x(L). The activation of JNK and
      MAPK kinase, which regulate these transcription factors, was reduced in Bcl-x(L)
      transfected cells. Overall, our results demonstrate that Bcl-x(L) inhibits TNF
      signaling at an early step common to induction of activation of apoptosis, NF
      kappaB, AP-1, MAPK, and JNK.

PMID- 10954918
TI  - A distinct element involved in lipopolysaccharide activation of the tumor
      necrosis factor-alpha promoter in monocytes.
AB  - To delineate the functional role of the tumor necrosis factor-alpha (TNF-alpha)
      activator protein-1 (AP-1)/cAMP-responsive element (CRE)-like binding element
      (TAC), we transfected the TNF-alpha promoter lacking TAC into THP-1 monocytic
      cells and stimulated with lipopolysaccharide (LPS). Chloramphenicol
      acetyltransferase (CAT) activity was reduced by 22-fold, suggesting that TAC
      plays a role in LPS induction of the TNF-alpha promoter. Exposure to LPS resulted
      in the maximum release of soluble TNF-alpha by 2 h. Electrophoretic mobility
      shift assays (EMSA) using the TAC element as a probe showed a unique pattern for
      LPS-activated cells: the disappearance of the upper band of a doublet seen in
      untreated and all-trans retinoic acid (ATRA)-treated cells. Supershift analysis
      identified c-Jun and activating transcription factor-2 (ATF-2) as components of
      the LPS-stimulated binding complex. Jun N-terminal kinase (JNK), a known
      phosphorylator of c-Jun and ATF-2, increased in activity in LPS-stimulated
      monocytes. ATRA, on the contrary, did not activate JNK activity up to 72 h.
      Nuclear extracts from LPS-stimulated cells showed an increase in phosphorylated c
      Jun by immunoblotting. Likewise, phosphorylated c-Jun bound to the TAC element,
      suggesting that c-Jun is activated by JNK to transactivate the TNF-alpha promoter
      in LPS-treated monocytes. Thus, phosphorylated c-Jun and ATF-2 play a role in
      activating the TAC element of the TNF-alpha promoter.

PMID- 10954917
TI  - Independent origin of IFN-alpha and IFN-beta in birds and mammals.
AB  - Phylogenetic analysis of type I interferon (IFN) from birds and mammals strongly
      supported the hypothesis that the gene duplication giving rise to the alpha and
      beta families of mammalian IFN occurred after the divergence of birds from
      mammals, whereas the bird IFN that have been designated alpha and beta duplicated
      independently in the avian lineage. Therefore, IFN designated alpha and beta in
      birds are not orthologous to those similarly designated in mammals.

PMID- 10954919
TI  - An ode to Osler.

PMID- 10954920
TI  - Harry Leach MRCP (1836-1879): control of scurvy in the British Mercantile Marine,
      and first Port Medical Officer for the city of London.

PMID- 10954921
TI  - Gustav Simon (1824-1877) and the development of nephrectomy: the surgeon and his
      intention.

PMID- 10954922
TI  - William Stark (1740-1770): his life, manuscript and death.

PMID- 10954923
TI  - Joseph Black (1728-1799): an early adept in quantification and interpretation.

PMID- 10954924
TI  - Sir Geoffrey Jefferson (1886-1961): a founder of British neurosurgery.

PMID- 10954926
TI  - Murray of the Middlesex.

PMID- 10954925
TI  - Biographies of the first lecturers at the Long Island College Hospital, the first
      medical school in Brooklyn.

PMID- 10954927
TI  - The Baron Doctor Cornelius Ver Heyden De Lancey: his foundation and benefactions.

PMID- 10954928
TI  - Renkioi revisited--postscript.

PMID- 10954930
TI  - Sir Charles Wyndham (1837-1919).

PMID- 10954929
TI  - The diagnosis and management of Crown Prince Friedrich's laryngeal tumour.

PMID- 10954931
TI  - Refugees, asylum seekers, and general practice: room for improvement?

PMID- 10954932
TI  - The impact of hepatitis C in general practice.

PMID- 10954933
TI  - Psychological distress and somatisation as prognostic factors in patients with
      musculoskeletal illness in general practice.
AB  - BACKGROUND: Musculoskeletal illness is a common cause of absenteeism from work,
      workers' compensation, and disability retirement, and accounts for 9.3% to 17% of
      patient contacts in general practice. To understand the increase in self-reported
      musculoskeletal illness and to improve treatment and prevention, it is important
      to know which factors to target when dealing with these patients. AIM: To
      investigate whether the prognosis for patients with musculoskeletal illness
      referred to physiotherapy from general practice can be predicted by the presence
      of psychological distress and somatisation identified by a general practitioner
      (GP) and standard questionnaires. METHOD: A multi-practice survey based on
      questionnaires (index and three-month follow-up). Nine hundred and five
      consecutive patients referred to physiotherapy from 124 different general
      practices in Denmark were included. Outcome measures were physical health change,
      sick leave, patient self-rated improvement, and change in use of medication.
      RESULTS: Psychological distress and somatisation rated by both GPs and standard
      questionnaires acted with almost no exception as significant predictors of all
      four outcome measures. CONCLUSION: Psychological distress and somatisation are
      important factors when considering preventive initiatives and treatment of
      patients with musculoskeletal illness in general practice.

PMID- 10954934
TI  - A survey of diabetes care in general practice in England and Wales.
AB  - BACKGROUND: The focus of care for people with diabetes has shifted from hospital
      to general practice. Many practices now offer diabetes care via dedicated mini
      clinics, shared care schemes or opportunistically. There has never been a
      national survey of the organisation of diabetes care in general practice. AIM: To
      describe some key features of diabetes care in primary care in England and Wales.
      METHOD: Descriptive postal questionnaire survey to one in five (1873) randomly
      sampled general practices. RESULTS: Seventy per cent (1320) of practices
      responded. Of these, 96% had diabetes registers identifying 1.9% of their
      population as having diabetes; 71% held clinics run by a general practitioner
      (GP) and a nurse (64%) or a nurse alone (34%); 80% felt adequately supported; and
      54% shared patient management protocols with the local secondary care team.
      Overall, practices provided most of the routine diabetes care for 75% of their
      diabetic patients. The majority of GPs and practice nurses had received some
      recent, albeit brief, diabetes education. CONCLUSION: A large proportion of
      diabetes care now takes place in the community, much of it delivered by practice
      nurses. The organisational infrastructure necessary for delivering good care is
      in place. Many practices have a special interest in diabetes with the majority
      feeling adequately supported by secondary care. However, there are concerns about
      the educational needs of those providing care. More work needs to be done to
      ensure seamless care across the primary-secondary care interface.

PMID- 10954935
TI  - Experience of heroin overdose among drug users attending general practice.
AB  - BACKGROUND: Heroin overdose is responsible for significant mortality. It has not
      previously been highlighted as an important prevention or care issue for general
      practitioners (GPs) involved in the management of drug misuse. AIMS: To examine
      the prevalence and experience of heroin overdose in a population of drug users
      attending a general practice. METHOD: A questionnaire-based interview of drug
      users attending a general practice in Dublin, Ireland. RESULTS: Twenty-four (73%
      of estimated total) drug users were interviewed. Although 17 (71%) were on
      recognised methadone treatment programmes, 10 (42%) were still injecting heroin.
      A total of 23 (96%) had witnessed an overdose, with 10 (42%) having been victims
      of overdose themselves. Twenty-two (92%) knew a victim of fatal overdose, with
      four (17%) having been present at a fatal overdose. The interviews revealed high
      levels of activity associated with overdose and poor use of preventive measures.
      CONCLUSION: The issue of prevention and management of overdose should become a
      priority for GPs caring for opiate-dependent patients.

PMID- 10954936
TI  - Young teenagers' attitudes towards general practitioners and their provision of
      sexual health care.
AB  - BACKGROUND: Pregnancy rates in under-16-year old teenagers and sexual risk-taking
      are both increasing. Ensuring that teenagers access health care--particularly
      sexual health care--appropriately is problematic. AIM: To find out the opinions
      and attitudes of 13- to 15-year-old teenagers towards general practice-based
      sexual health care services. METHOD: A quantitative survey, using a questionnaire
      completed during school hours. RESULTS: One thousand and forty five children aged
      13 to 15 years completed questionnaires. The majority (709 [68%]) were aware of
      the sexual health services offered by general practitioners (GPs), and 786 (75%)
      were positive about being given helpful advice at a consultation. However, 567
      (54%) teenagers believed they had to be over 16 years old to access sexual health
      services and 604 (58%) were concerned about their confidentiality not being
      preserved by their GP. They were also concerned about GPs not having the time or
      skills to deal with their problems (314 [30%]). CONCLUSIONS: This study suggests
      that work is needed to improve teenagers' access to, and use of, primary care
      sexual health services. In particular, identifying strategies that improve
      teenagers' awareness of services and general practitioners' approaches towards
      teenagers are priorities.

PMID- 10954937
TI  - A cost consequence study of the impact of a dermatology-trained practice nurse on
      the quality of life of primary care patients with eczema and psoriasis.
AB  - BACKGROUND: The practice nurse is central to the development of a primary care
      led National Health Service. Skin diseases can have a major impact on patients'
      lives but general practitioners (GPs) lack many of the skills of practical
      dermatology care and support. AIM: To determine whether a primary care
      dermatology liaison nurse should be introduced by our health authority. We
      identified the resources consumed and the benefits that accrued from a practice
      nurse who had received training in practical dermatology care. METHOD: A cost
      consequence study in parallel with a randomised controlled trial was undertaken
      in a group of nine GPs and 109 patients between the ages of 18 and 65 years who
      had a diagnosis of psoriasis or eczema. RESULTS: Although there was a significant
      improvement in our primary outcome measure within group, when compared with the
      control group significance was not achieved. There was no significant change in
      the Euroqol measure but the clinical instrument showed a significant change when
      compared with control. On entry, our qualitative data identified three main
      themes--the embarrassment caused by these skin conditions, the wish for a cure
      rather than treatment, and concern over the long-term effects of steroids. On
      completion, 20% of patients expressed that they had received a positive benefit
      from the clinic. CONCLUSION: This study demonstrates the difficulties of
      obtaining relevant information to facilitate decisions on how resources should be
      allocated in primary care. Not all questions can be answered by large multi
      centred trials and studies themselves have an opportunity cost consuming
      resources that could otherwise be spent on direct health care. Often, local
      resource decisions will be based on partial evidence-yielding solutions that are
      satisfactory rather than optimum but which are, nevertheless, better than
      decisions taken with no evidence at all.

PMID- 10954938
TI  - Are there age and sex differences in the investigation and treatment of heart
      failure? A population-based study.
AB  - BACKGROUND: Heart failure is a serious, common, and growing problem. Hospital
      admissions, which account for the bulk of health service costs associated with
      heart failure, are becoming more frequent. AIM: To determine whether management
      of heart failure differs by age and sex. METHOD: A retrospective case note review
      of prevalent cases in 16 general practices in West London. Five hundred and
      eighty-three patients (57% women) with a diagnosis of heart failure were
      reviewed. RESULTS: Mean age of patients with heart failure was 78 years (SD =
      9.5)--74 years at diagnosis (SD = 10)--and was higher for women than men (76
      years versus 71 years, P < 0.001). In 32% of patients there was no record of a
      chest X-ray, electrocardiogram, or echocardiogram to support diagnosis.
      Echocardiography, performed in 34% of patients, was less likely in older patients
      in both sexes (test for trend P = 0.04 in women and 0.02 in men) and, overall, in
      women (29% compared with 40% of men, P = 0.006). Angiotensin-converting enzyme
      (ACE) inhibitor treatment, recorded in 54% of patients, decreased with age in
      both sexes (P < 0.001) and, on unadjusted data, was more likely in men than in
      women (61% compared with 49%, P = 0.005). On adjustment for age, sex differences
      in the use of echocardiography and ACE inhibitors were reduced and no longer
      significant. CONCLUSIONS: With increasing age, men and women with heart failure
      were less likely to have undergone echocardiography or to have received an ACE
      inhibitor. When account was taken of age, there were no statistically significant
      sex differences in management; however, because of the demographic distribution
      of heart failure, women are disproportionately affected by age differences in
      management. Clinical trials, physician practice, and service developments in
      heart failure have neglected older people. This balance should be redressed.

PMID- 10954939
TI  - Trends in negative defensive medicine within general practice.
AB  - Negative defensive medical practice has adverse consequences both for individual
      patients and for public health. This paper reports the results from a survey
      conducted in 1999 in which certain features indicative of negative defensive
      practice were compared with an identical survey conducted five years previously.
      Responding general practitioners stated that they are now significantly more
      likely to undertake diagnostic testing, refer patients, and avoid the treatment
      of certain conditions.

PMID- 10954940
TI  - Do British travel agents provide adequate health advice for travellers?
AB  - Travel-related illness is a burden for primary care, with more than two million
      travellers consulting a general practitioner each year. The annual cost of travel
      related illness in the United Kingdom is 11 million Pounds. Travel agents are in
      a unique position to influence this burden as the most common and most serious
      problems are preventable with simple advice and/or immunisation. This study,
      using covert researchers, suggests this potential is not being fully utilised.

PMID- 10954941
TI  - Unresolved grief in young offenders in prison.
AB  - The study aimed to pilot a grief awareness programme as a health promotion
      project for young offenders with complicated grief. Seventeen young offenders in
      custody at HM Prison, Cardiff were opportunistically recruited, interviewed about
      their bereavement, and offered entry to the programme. Young offenders who
      reported coping poorly with bereavement were more likely to have used drugs to
      cope with their emotions, to have had suicidal thoughts, and reported more
      depression and anxiety. They were also more likely to have been bereaved in late
      adolescence and to have lost a first degree relative, with death being sudden,
      violent or by suicide.

PMID- 10954942
TI  - Making research relevant to the primary health care team.
AB  - There is, as yet, no strong culture of research in primary care and much of the
      existing research is conceived and undertaken by people outside primary care. The
      poor implementation of research findings may, in part, be owing to the fact that
      those delivering the service are not involved in asking or answering questions
      that are relevant to their practice. This paper reports how three practices
      constructed a research agenda based on the unanswered questions of their primary
      care teams. The research questions prioritised by the teams tended towards
      patient behaviour and service organisation rather than clinical issues. This
      contrasts with national research priorities. The process has contributed towards
      the development of a culture of enquiry among team members. Other primary care
      teams may benefit from a similar approach. National research priority setting in
      primary care should take more account of the unanswered questions of primary care
      teams.

PMID- 10954943
TI  - Helicobacter pylori infection: not associated with recurrent abdominal pain in
      children.

PMID- 10954944
TI  - Snakes and statistics: association does not prove causation.

PMID- 10954945
TI  - Negative predictive value of urine dipstick testing.

PMID- 10954946
TI  - Primary care in the United States.

PMID- 10954947
TI  - General Practice Morbidity Database Project.

PMID- 10954948
TI  - Neanderthals, doctors, and computers.

PMID- 10954949
TI  - Patient's partnership.

PMID- 10954950
TI  - Turning up the heat on doctors' performances.

PMID- 10954951
TI  - GP opportunities for teenage health promotion.

PMID- 10954952
TI  - Systolic heart failure: no room for complacency.

PMID- 10954953
TI  - A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal
      spray in the acute treatment of migraine.
AB  - A multinational, multicentre, randomised, double-blind, double-dummy, crossover
      study (368 patients treating two attacks) was conducted to compare the efficacy
      and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE)
      nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60
      minutes after dosing, significantly more patients obtained headache relief
      (change from moderate or severe to none or mild) after treatment with sumatriptan
      than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients
      reported relief of nausea after sumatriptan than after DHE at 60 minutes (64%
      sumatriptan, 49% DHE, p = 0.006). A significant difference between the two
      treatments was first observed at 45 minutes with respect to both headache relief
      (38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40%
      DHE, p = 0.014). There were no significant differences between the two treatments
      for other measures of efficacy. Both treatments were well tolerated, with only
      10% of patients in each group reporting one or more adverse events. The most
      frequently reported adverse event after sumatriptan was a bad or bitter taste,
      which was reported by 5% of patients. After DHE, 4% of patients reported symptoms
      of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse
      events. It is concluded that sumatriptan nasal spray is superior to DHE nasal
      spray in the relief of pain and nausea associated with acute migraine headache.

PMID- 10954954
TI  - Cost-effective prescribing of proton pump inhibitor therapy: an audit in general
      practice.
AB  - General practitioners must prescribe cost effectively to control drug expenditure
      and provide optimal treatment for patients requiring long-term management. An
      audit was implemented in general practices to review the management of dyspepsia,
      improve care, rationalise therapy and reduce costs. Policy included identifying
      patients receiving proton pump inhibitor (PPI) therapy and changing to low-dose
      cost-effective therapy. If PPI therapy was not required, patients were changed to
      antacids, H2 receptor antagonists or no treatment. This was an audit in general
      practice, not a clinical trial, therefore findings reflect outcomes in normal
      clinical practice. This paper describes the implementation and findings of the
      audit between January 1997 and July 1999 in 91 general practices involving 7121
      patients. Extrapolation of the results concluded that savings of up to 50,000
      Pounds could be made in a practice of 10,000 patients, allowing reinvestment in
      health improvement plans and optimal care.

PMID- 10954955
TI  - A comparison of a five-day regimen of cefdinir with a seven-day regimen of
      loracarbef for the treatment of acute exacerbations of chronic bronchitis.
AB  - To compare the efficacy and safety of five-day cefdinir treatment with seven-day
      loracarbef treatment in patients with acute exacerbations of chronic bronchitis,
      586 patients were enrolled in a multicentre, randomised, double-blind trial.
      Patients received either five days of treatment with cefdinir (n = 291) at 300 mg
      twice daily or seven days of treatment with loracarbef (n = 295) at 400 mg twice
      daily. Microbiological assessments were done on sputum specimens obtained at
      admission and at the two post-therapy visits, if available. The clinical cure
      rates were 86% (138/160) and 85% (141/166) for the evaluable patients treated
      with cefdinir and loracarbef, respectively. Respiratory tract pathogens were
      isolated from 457 (78%) of 586 admission sputum specimens, with the predominant
      pathogens being Haemophilus parainfluenzae, H. influenzae, Moraxella catarrhalis
      and Staphylococcus aureus. The microbiological eradication rates at the test-of
      cure visit were 88% (193/219 pathogens) and 90% (227/251 pathogens) for the
      evaluable patients treated with cefdinir and loracarbef, respectively. Adverse
      event rates while on treatment were 30% and 21% for cefdinir- and loracarbef
      treated patients, respectively. These results indicate that a five-day regimen of
      cefdinir is effective and safe for the treatment of patients with acute
      exacerbations of chronic bronchitis.

PMID- 10954957
TI  - Low density lipoprotein cholesterol lowering: are the treatment guidelines still
      appropriate?
AB  - The availability of treatment guidelines has revolutionised our approach to
      detection, evaluation and treatment of dyslipidaemias in adults. Such guidelines
      focus on lowering low-density lipoprotein-cholesterol (LDL-C), the primary risk
      factor for coronary heart disease, and provide physicians with specific goals to
      be attained by dietary and, if necessary, pharmacological therapy. However, the
      guidelines were published in 1993, which means that the pivotal findings from
      large intervention trials with statins were not included. This has led to calls
      for the guidelines to be amended to take into account the findings of these
      studies and other evolving issues such as the pathogenesis of the acute coronary
      event and the contribution of low HDL-C and other lipid parameters. More
      importantly, the mostly epidemiological basis of the guidelines has instilled the
      concept that the lower the LDL-C level after lipid-lowering intervention the
      better the result in terms of prevention of coronary events. Available data now
      refute this assumption. Indeed, maximal therapeutic benefit is already obtained
      with a decrease in LDL-C level of 20-30%, irrespective of baseline levels or LDL
      C levels on treatment and, until now, there have been no data to suggest that
      decreases in LDL-C of > 30% give any additional benefit to patients in terms of
      improving their long-term outcome. The concept of absolute LDL-C treatment goals
      therefore needs to be revisited. A more appropriate goal of lipid-lowering
      therapy with statins is to ensure LDL-C levels are reduced by 20-30%, with statin
      dosages as used in the intervention trials. Furthermore, there are insufficient
      data to advise that LDL-C levels should be lowered to 2.6 mmol/l. This issue will
      be resolved only when the results of the appropriate intervention trials are
      published.

PMID- 10954956
TI  - A comparison of patients admitted to two medium secure units, one for those of
      normal intelligence and one for those with learning disability.
AB  - Differences between patients being treated in two different medium secure units,
      one for those of normal intelligence and one for those with learning disability,
      were investigated. Sociodemographic, psychiatric, medical and medicolegal data
      were recorded for all inpatients in both secure units. Patients in the medium
      secure unit for those of normal intelligence were older at the time of the study
      and at conviction for the index offence, more likely to have been admitted from
      the penal system, and more likely to suffer from a psychotic disorder,
      particularly schizophrenia or a mood disorder. Their index offence was more
      likely to be homicide, attempted murder, manslaughter or grievous bodily harm,
      while that of the patients with learning disability was more likely to be a
      sexual offence. A need for separate medium secure unit facilities for those of
      normal intelligence and those with learning disability is supported by differing
      psychiatric and behavioural requirements.

PMID- 10954958
TI  - Hypermobility--not a circus act.
AB  - Joint hypermobility results from genetic variations in connective tissue matrix
      proteins resulting in stretchier tissues. For many it is an asset that confers
      greater facility for physical prowess. Others, less fortunate, fall prey to the
      associated effects of tissue fragility. The most frequently encountered
      constellation of traumatic and overuse injuries is termed the (benign joint)
      hypermobility syndrome (BJHS). This condition, poorly understood, frequently
      overlooked, misdiagnosed and inappropriately treated, is the cause of much
      needless suffering and anguish. Accumulating evidence suggests that BJHS
      represents a forme fruste of an heritable disorder of connective alongside Marfan
      syndrome, Ehlers-Danlos syndrome and osteogenesis imperfecta, with which it
      shares many overlapping features, but from which it can be phenotypically
      distinguished on the basis of clinical features and prognosis. The responsible
      gene defects have yet to be elucidated.

PMID- 10954959
TI  - Evidence-based counselling for vasectomy.
AB  - Couples requesting vasectomy need to be properly counselled. Vasectomy is
      generally safe but it can fail in up to 6% of cases. Reversal is possible but not
      always successful. Most men are azoospermic six weeks after vasectomy. They must
      be warned that the procedure may have to be repeated if there are persistent
      motile sperm in their post-vasectomy semen analysis.

PMID- 10954961
TI  - Moxifloxacin (Avelox): an 8-methoxyquinolone antibacterial with enhanced potency.
AB  - Moxifloxacin is a novel 8-methoxyquinolone with enhanced potency against
      important Gram-positive pathogens, notably Streptococcus pneumoniae. It retains
      class activity against Gram-negative bacteria. Currently available for oral use,
      it has a prolonged half-life, enabling once-daily administration and reflecting
      balanced renal and hepatic elimination. Clinical trials have demonstrated an
      excellent safety record with minor class effects in the skin and gastrointestinal
      systems. Potential for phototoxicity is minimal and moxifloxacin is free of
      clinically significant neurological, hepatic or cardiac effects. Investigated
      primarily in respiratory infections, moxifloxacin has shown excellent performance
      in community-acquired pneumonia (both pneumococcal and atypical), acute
      exacerbations of chronic bronchitis and acute maxillary sinusitis. It is
      available in many European countries and in the US where it is rapidly
      establishing clinical acceptance and formulary inclusion.

PMID- 10954960
TI  - Anaphylaxis and anaphylactoid reactions.
AB  - The clinical syndrome of anaphylaxis and anaphylactoid reactions is quite
      variable, making diagnosis difficult at times. Early recognition by patient or
      physician is imperative to appropriate management. Recurrences may be life
      threatening if the initial diagnosis is incorrect, as patients do not avoid the
      offending allergen. Release of inflammatory mediators from mast cells and
      basophils are responsible for the symptoms and signs in both anaphylactic and
      anaphylactoid reactions. They differ only in the initial cause of the activation
      of the mast cell or basophil. Management, regardless of the cause, involves rapid
      treatment. Intravenous fluids and adrenalin (preferably intravenous if
      appropriate) usually produce a response in more than 90% of patients. Prevention
      strategies including pharmacological prophylaxis should not be undervalued,
      because recurrences can easily be avoided. Follow-up with an
      allergist/immunologist is essential.

PMID- 10954962
TI  - Rosiglitazone.
AB  - Rosiglitazone, a potent thiazolidinedione oral antidiabetic agent recently
      approved in the US, differs structurally from pioglitazone and troglitazone
      (other approved thiazolidinediones), with greater PPAR gamma binding affinity and
      antihyperglycaemic potency in preclinical models. Clinical data on more than 4500
      patients with type 2 diabetes show that rosiglitazone is a safe, effective
      monotherapy or combination therapy, producing significant reductions in
      haemoglobin A1c and fasting plasma glucose under different dosing regimens.
      Unlike troglitazone, which has been associated with idiosyncratic hepatotoxicity
      and rare cases of liver failure and death, rosiglitazone has shown a low
      incidence of liver abnormalities in more than 3500 patient-years of exposure. No
      significant food or drug interactions have been reported. Particularly effective
      as first-line therapy, rosiglitazone is a useful addition to the roster of oral
      antidiabetic agents.

PMID- 10954963
TI  - Colonic perforation associated with slow-release diclofenac sodium.
AB  - Upper gastrointestinal tract complications due to non-steroidal anti-inflammatory
      drugs are well recognised. However, adverse effects on large intestinal mucosa
      are less common and less well recognised, even though they carry a significant
      morbidity and mortality. Here we report a case of colonic perforation in a
      healthy woman without any underlying colonic pathology associated with ingestion
      of slow release diclofenac sodium.

PMID- 10954964
TI  - Ischaemic myelopathy presenting as Guillain-Barre syndrome.
AB  - Spinal cord stroke is uncommon. We report a woman presenting with paraesthesia
      followed by tetraparesis and respiratory failure who was initially diagnosed as
      having Guillain-Barre syndrome. Subsequent clinical and imaging features
      supported the diagnosis of an anterior spinal cord infarction. We describe the
      main clinical and imaging features of this condition.

PMID- 10954965
TI  - First branchial groove anomaly.
AB  - First branchial groove anomalies are very rare. We report a case of a first
      branchial groove anomaly presented as an infected cyst in an 11-month-old child.
      Management of such lesions is complicated because of their close association with
      the facial nerve. Surgical management must include identification and protection
      of the facial nerve. Embryology and facial nerve disposition in relation to the
      anomaly are reviewed.

PMID- 10954966
TI  - Refractory Bacillus cereus infection in a neonate.
AB  - Bacillus cereus is a Gram-positive aerobic or facultatively anaerobic spore
      forming rod, which usually causes food poisoning. Its recognition as a pathogen
      in neonates has increased over the past two decades. The clinical course of a
      neonate (gestation 24 weeks) with B. cereus infection refractory to therapy is
      described. Death occurred after withdrawal of support following persistently
      positive blood and bone marrow cultures despite therapy with vancomycin,
      gentamicin, imipenum, clindamycin, ciprofloxacillin, immunoglobulin and
      granulocyte colony stimulating factor over a period of 49 days. No obvious focus
      of sepsis was identified. Contamination from the environment into the hospital
      and clinics occurs because of the ubiquitous presence of B. cereus. Combination
      therapy with vancomycin and gentamycin is appropriate for meningitis/severe
      systemic infections related to most bacillus species. The significance of
      repeated isolation of B. cereus in neonates with compromised host defences is
      emphasised.

PMID- 10954967
TI  - The monthly malady: a history of premenstrual suffering.

PMID- 10954968
TI  - Medical statistics, patronage and the state: the development of the MRC
      Statistical Unit, 1911-1948.

PMID- 10954970
TI  - The study of the human remains from Nubia: the contribution of Grafton Elliot
      Smith and his colleagues to palaeopathology.

PMID- 10954969
TI  - Was the huey cocoliztli a haemorrhagic fever?

PMID- 10954971
TI  - Wellcome and "The great past".

PMID- 10954973
TI  - Monitoring child growth.

PMID- 10954974
TI  - A belligerent patient who makes threats.

PMID- 10954975
TI  - Re-evaluating the ENT procedures.

PMID- 10954977
TI  - 'Mummy, I can't sleep'.

PMID- 10954976
TI  - The GP strategy for headaches in children.

PMID- 10954978
TI  - The child with slow language development.

PMID- 10954979
TI  - Pitfalls in the management of children with wheeze.

PMID- 10954980
TI  - Why history is the key in the diagnosis of vertigo.

PMID- 10954981
TI  - The patient with primary open-angle glaucoma.

PMID- 10954982
TI  - The educational and communication needs of deaf and hard of hearing children: a
      statement of principle on fundamental educational change.

PMID- 10954984
TI  - 'Down to skin and bone'.

PMID- 10954983
TI  - Skin infections and infestations in Aboriginal communities in northern Australia.
AB  - The most important skin infections in Aboriginal communities in central and
      northern Australia are scabies and streptococcal pyoderma. Scabies is endemic in
      many remote Aboriginal communities, with prevalences in children up to 50%. The
      cycles of scabies transmission underlie much of the pyoderma. Up to 70% of
      children have skin sores, with group A streptococcus (GAS) the major pathogen.
      Group A streptococcus is responsible for the continuing outbreaks of post
      streptococcal glomerulonephritis and acute rheumatic fever (ARF). The cycles of
      scabies transmission in dogs and humans do not appear to significantly overlap.
      Guidelines have been developed for community control of scabies and skin sores
      and successful community initiated coordinated programmes have occurred. The
      anthropophilic dermatophyte Trichophyton rubrum is ubiquitous in many
      communities, again reflecting living conditions. Other skin infections related to
      the tropical environment include melioidosis, nocardiosis, Chromobacterium
      violaceum and chromoblastomycosis. Sustainable and long-term improvements in
      scabies, skin sores and GAS-related disease and tinea require fundamental changes
      that address social and economic inequities and, in particular, living conditions
      and overcrowding.

PMID- 10954985
TI  - Defining lymphocytic vasculitis.
AB  - Vasculitis can be defined as vascular inflammation which is usually immune
      mediated, leading to structural and functional damage to the vessel wall. Our
      concept of vasculitis has been built around the events surrounding immune-complex
      triggered leukocytoclastic vasculitis, while the role of lymphocyte mediated
      vasculitis remains largely undefined. This may be due to maintaining a
      stereotypic image of lymphocytic vasculitis as one associated with vascular
      necrosis, fibrin deposition and haemorrhage and merely substituting lymphocytes
      for neutrophils. Our understanding of lymphocytic vasculitis may be advanced by
      identifying the clinical settings in which such reactions may occur, such as
      autoimmune skin diseases sharing features with graft vs host disease, as well as
      recognizing that lymphocyte mediated inflammation may lead to a morphologically
      distinct group of vasculitides, apart from those associated with
      angiodestruction. Lymphocytic endovasculitis, lymphocytic lichenoid vasculitis
      and granulomatous vasculitis are potential examples of lymphocytic vasculitis
      that differ from the histological pattern seen in association with immune complex
      leukocytoclastic vasculitis. Ultimately, the proof that these vasculitides are
      examples of lymphocytic vasculitis will rest on new techniques emerging in
      molecular pathology that have the capacity of analysing the immunological events
      beyond the current limitations posed by routine histopathology.

PMID- 10954986
TI  - Dermatological presentations of infantile myofibromatosis: a review of 27 cases.
AB  - Twenty-seven cases of infantile myofibromatosis presenting with dermatological
      manifestations were retrospectively reviewed. Approximately 80% were solitary
      lesions and 50% of these appeared on the head and neck. Around 60% were present
      at or soon after birth. Most lesions were dermal or subcutaneous, although some
      were intramuscular and intraosseous. The clinical appearance was non-specific
      leading to frequent misdiagnosis. While most patients presented with nodules,
      atrophic depressed lesions and warty pedunculated lesions were also seen.
      Although 7% of lesions recurred after excision, spontaneous resolution was also
      documented.

PMID- 10954987
TI  - Whiplash rove beetle dermatitis in central Queensland.
AB  - Vesicular dermatitis due to contact with Coleoptera (beetles) is common
      worldwide, although the condition has been infrequently described in Australia.
      We document the largest outbreak recognized so far in Australia with a
      conservative estimate of 250 cases. This occurred in central coastal Queensland
      over several weeks in late 1998. A survey of the medical practitioners in this
      district is presented, along with clinical and histopathological illustrations.
      Our research found that knowledge of the condition was limited even in this
      region where cases occur each year. This condition is an important differential
      diagnosis in acute blistering disorders.

PMID- 10954988
TI  - Severe allergic contact dermatitis induced by paraphenylenediamine in paint-on
      temporary 'tattoos'.
AB  - Paraphenylenediamine (PPD) is a black dye with well known sensitizing properties.
      Its increasing use as a skin paint to produce temporary 'tattoos' has led to
      recent reports of allergic contact dermatitis. Hitherto, such cases of allergic
      contact dermatitis due to PPD have been localized to the original site of
      application of the skin paint. We report two cases of severe allergic reactions
      to paint-on 'tattoos'. Both of these patients had no prior history of sensitivity
      to PPD, although case 2 had previously used permanent hair dyes. In both cases,
      the primary eruption at the 'tattoo' site was followed within days by a
      generalized eruption which ultimately required treatment with oral
      corticosteroids, because the initially prescribed topical corticosteroids proved
      ineffective.

PMID- 10954989
TI  - Transient reactive papulotranslucent acrokeratoderma associated with cystic
      fibrosis.
AB  - A 20-year-old female with cystic fibrosis presented with a white marginal palmar
      eruption after exposure to water. There was no family history of keratoderma. A
      biopsy showed hyperkeratosis around dilated eccrine ostia. These features are
      similar to a recently described condition, transient reactive papulotranslucent
      acrokeratoderma. This is thought to be a variant of hereditary papulotranslucent
      acrokeratoderma, one of the punctate keratodermas. Association with cystic
      fibrosis has not been described previously.

PMID- 10954990
TI  - Pachyonychia congenita tarda.
AB  - A 42-year-old man presented with painful toenails which were overcurved
      transversely and onycholytic. Examination revealed that all toenails, the thumbs
      and index fingers were similarly affected. In addition, he had a small area of
      leukokeratosis in the mouth, epidermal cysts of the scrotal skin and a small area
      of hyperkeratosis on the ulnar borders of his hands. His characteristic nail
      changes began in the great toenails at the age of 20 years. After renal
      transplantation at age 39, the other nails changed and he developed the features
      described above. His sister has overcurvature of the fifth toenails. A diagnosis
      of pachyonychia congenita tarda was made. His case is compared with 14 other
      reported cases of this rare syndrome.

PMID- 10954991
TI  - Pemphigus with pemphigoid-like presentation, associated with squamous cell
      carcinoma of the tongue.
AB  - A 53-year-old woman presented with an inoperable squamous cell carcinoma of the
      tongue associated with tense large bullae consistent with bullous pemphigoid,
      preceded by a prodrome of urticarial plaques. The histological findings showed a
      regenerating subepidermal blister with eosinophils and no acantholysis. Direct
      immunofluorescence study, however, showed positive staining for IgG and C3
      throughout the epidermis consistent with pemphigus. The blistering eruption had
      no mucosal involvement and responded to low dose corticosteroids. Our patient may
      represent another presentation of a 'paraneoplastic pemphigus spectrum'.

PMID- 10954992
TI  - Drug-induced solar urticaria due to tetracycline.
AB  - Solar urticaria is an uncommon disorder characterized by pruritus, erythema and
      whealing commencing within minutes of exposure to ultraviolet (UV) and visible
      light, and generally resolves in a few hours. We describe a 28-year-old woman who
      developed pruritus and erythema 5 min after sun exposure while on tetracycline
      for treatment of perioral dermatitis. Phototesting elicited urticarial reactions
      in the UVA, UVB and visible spectra. Repeat phototesting after cessation of
      tetracycline was negative. This report documents the first case of solar
      urticaria induced by tetracycline.

PMID- 10954993
TI  - Multiple piloleiomyomas.
AB  - A 21-year-old female developed multiple painful flesh-coloured papules over the
      anterior chest. Skin biopsy was consistent with a diagnosis of piloleiomyomas.

PMID- 10954994
TI  - Sjogren's syndrome and granulomatous panniculitis.
AB  - An 83-year-old Cambodian woman presented with multiple painful erythematous
      nodules on the lower legs, forearms and wrists. Subsequent history and
      investigations revealed a granulomatous lobular panniculitis associated with
      Sjogren's syndrome. This is a rare cutaneous association of Sjogrens syndrome
      with only three similar case reports in the literature.

PMID- 10954995
TI  - 1,6-hexanediol diacrylate: a rapid and potent sensitizer in the printing
      industry.
AB  - Printers are exposed to a wide variety of irritants and sensitizers. Allergy
      developing from a single exposure to any compound is rare. We report two cases of
      workers in the printing industry who developed allergic contact dermatitis to 1,6
      hexanediol diacrylate (HDDA) within a short period of exposure. The first
      developed within weeks of exposure to a plastic sheet primed with HDDA. The
      second developed after a single accidental exposure.

PMID- 10954996
TI  - [Healing process of claw lesions in dairy cows in alpine mountain pastures].
AB  - The field study investigated severity, localisation and incidence of claw lesions
      of dairy cows and their healing process during a period of three months on
      selected mountain pastures in the central part of Switzerland. In 60 cows, which
      were at least 120 days in their lactation, the healing process was compared with
      the biochemical profiles. In 141 cows 197 claw lesions were recorded. Diagnosed
      were only sole ulcers (38%) and white line lesions (62%). In the first and second
      half of the summer term, the number of claw lesions was equal, although more
      severe lesions occurred mainly during the second half (89%). The lesions were
      treated surgically and the affected claw was elevated on a wood block or a
      plastic shoe. Average time for formation of a close layer of horn was 14 days. A
      delayed healing process was observed in dairy cows with an milk yield over 5500
      kg per lactation, as well as in the second half of the summer term. Cows with a
      delayed healing process had significantly higher concentrations of free fatty
      acids and beta-hydroxybutyrate, and higher plasma enzyme activities for AST than
      cows with adequate healing process. This indicates that cows with a relatively
      high milk production touch upon the limits of their physical capacity under
      harder conditions on alpine pastures, which may affect also the healing process
      of claw lesions.

PMID- 10954997
TI  - [Importance of herd management in loose housing systems in the social behavior of
      dairy cows].
AB  - In five loose housed dairy herds three different kinds of herd management were
      tested in two variants with respect to frequencies of agonistic social behaviour.
      Treatments were (1) a short (0.5 h) and a long (3 h) fixation time in the feeding
      rack, (2) single and group (3 animals) introduction of new heifers into the herd
      and (3) an open and a closed outdoor yard during nighttime. The investigated
      agonistic behaviour patterns were: pushing and chasing. The herds were observed
      in the evening after milking during one four-hour period starting one hour after
      opening the feeding rack when testing treatment (3) and immediately after opening
      the feeding rack when testing treatment (1) and (2). Statistical analysis were
      carried out with the Wilcoxon signed-ranks test for matched samples. Effects of
      fixation time differed inconsistently and were not significant. In 3 out of 5
      farms the frequency of agonistic behaviour was lower, when cows were restrained 3
      h in the feeding rack compared to 0.5 h. In two of these 3 herds, the animals had
      the possibility to drink water from bowls directly at the feeding rack, in the
      third herd the food was silage which has a higher water content. Therefore in
      these herds, the agonistic interactions at the drinking facility in the stable
      after opening the feeding rack was low. Contrary, in the two other herds, with
      dry feed (hay) and no drinking bowls at the feeding rack, frequency of agonistic
      behaviour was higher after the long restraint which might be due to higher
      competition at the drinking facilities. Agonistic interactions per cow as well as
      per new introduced heifer were lower (p < or = 0.05) when only a single heifer
      was introduced to the herd compared to the introduction of a group of 3 heifers.
      The frequency of agonistic social behaviour of horned dairy cows that had access
      to a yard at night was significantly lower compared to the situation when the
      yard was closed over night (p < or = 0.05). This may be due to the higher space
      allowances per cow but also to the additional structuring of the locomotion area.

PMID- 10954998
TI  - [Effect pf genotype, age of dams, litter size, birth weight and rams on
      morphological parameters of the placenta in sheep].
AB  - It is well established that especially in prolific ewes the mortality rates are
      high in lambs with low birth weights and that after birth the absolute growth
      rates are lower in the surviving light lambs than in the heavier lambs.
      Differences in the prenatal placental development as the feto-maternal connection
      could be one of the reasons for this effect. The aim of the present study was to
      ascertain primary data for the placenta characteristics. Therefore three
      different genotypes which varied in litter size and weight of all born lambs were
      studied. In 197 placentas the weight, the number of cotyledones, the diameter of
      the cotyledones and the weight of ten cotyledones were determined. The total
      weight of all cotyledones and surface area of the cotyledones (the feto-maternal
      contact area) were calculated. The effects of the breed, the age of the dams (1.5
      7.5 years), the litter size (1-4), the weight of all born lambs (5 classes
      between 3 and 15 kg) and the ram were tested with the ANOVA/MANOVA procedure (co
      variable = weight of the dams before mating). Litter size and weight of all born
      lambs influenced significantly the morphologicaly parameters of the placenta. In
      the examined genotypes the placenta weight increased from a minimum of 500 g to
      1100 g and the surface of the cotyledones grew from 200 cm2 to 350 cm2 with
      increasing litter size and increasing weight of all born lambs. This seems to be
      a maternal compensation mechanism for the raising fetal requirements. With the
      increase of the litter size the surface area of the cotyledones for each lamb
      decreases because the possible placental compensation mechanism collapses. This
      could be a reason for low birth weights and increasing deaths of lambs. A
      possible influence of the genotype on the characteristics of the placentas is
      discussed by considering the litter size and the condition of the ewe. Paternal
      effects were not found.

PMID- 10954999
TI  - [Maintenance of African ostriches (Struthio carnelus) under Hessian climatic
      conditions--analysis of metereological data for the application of BML's expert
      recommendations of 1996].
AB  - A report is given on an analysis of meteorological data on five locations in the
      region of Hessia in order to apply the BML's expert recommendation concerning
      ostrich farming. According to this recommendation black ice, very strong frost
      and continuous rain should not make it necessary to keep the animals in pens
      longer than 3 days or more often than 10 days per month. Otherwise a dry paddock
      must be provided. It was investigated whether and how often the above mentioned
      weather conditions exceeded the critical duration or frequency in the last
      decades at the different locations. Previously the weather related terms which
      were used in the BML-recommendation were defined more precisely in order to
      provide an objective basis for the analysis. Frequent periods of frost lasting
      longer than 3 days with temperatures below -5 degrees C were found to be a
      critical factor. They occurred in 79 to 90% of the winter seasons under
      investigation, although the climate was thought to be rather mild in comparison
      to other regions. Frost can not be remedied by a dry paddock. Therefore the
      locations in question are not suitable for ostrich farming. The same conclusion
      holds at least for all locations with a colder climate. Black ice occurred only
      scarcely. At none of the investigated locations periods of continuous rain were
      longer than 3 days or occurred more often than 10 days per month. This result
      might not only be due to the given climatic conditions but also due to
      methodological reasons. It seems that the meteorological definition of continuous
      rain is too restricted to take the relevant precipitation for ostriches into
      account. It is suggested to find a new definition and consider factors like
      humidity and wind speed as well.

PMID- 10955000
TI  - [Werner Schafer. A life as researcher and teacher].
AB  - The following short biography recalls Professor Dr. Dr. h.c. Werner Schafer,
      emeritus professor and director of the Medical Biology Department of the Max
      Planck-Institut fur Virusforschung in Tubingen and scientific member of the Max
      Planck Society who died on 25th April 2000. He was one of the most distinguished
      pioneers of animal virology and one of the great personalities who since the
      Second World War have helped German science to regain its international
      reputation. In a brief synopsis the important results of his work on the viruses
      he used as models to conduct his research have been portrayed. As a result of
      Schafer's scientific conception to gain insights into the functional
      characteristics of viruses by looking at their structure, the field of virology
      has taken new directions and founded a school whose pupils try to continue his
      successful and much honoured life's work.

PMID- 10955001
TI  - [Social medicine in social work--a key for improving health-related social work].
AB  - The relation between social work and social medicine is the subject of this
      article. Social work is an independent discipline creating its own knowledge in
      scientific cooperation with other disciplines. Social Medicine is outlined with
      its special features as a field and as a medical discipline. The traditional
      relation between social work and the discipline of Social Medicine operates side
      by side. Since Social Medicine and social work refer to each other, new
      perspectives for the development of health-related social work arise. Social
      Medicine appeared in social work can help in elaborating a sociogenetic model of
      understanding health and illness as well as the development of sociotherapy in
      social work. Health-related social work will gain more significance in the
      treatment of health-related and disease-related questions.

PMID- 10955002
TI  - [Incidence of operations in Germany via telephone survey in 4 selected cities].
AB  - Considerable regional variation of surgical procedure rates has been reported for
      a number of countries. Influential variables that have been discussed are patient
      related, physician-related and health care system-specific factors. A
      representative computer-assisted telephone survey was conducted in four selected
      regions for a study sponsored by the German Federal Ministry of Health. These
      regions were the townships of Aachen and Hamm in North Rhine-Westphalia and
      Chemnitz and Gorlitz in Saxony. During the telephone survey 1897 persons were
      contacted and 1041 interviews completed. Multiple logistic regression showed a
      surgical procedure frequency which was by 40% higher in Aachen than in Hamm.
      During further analysis the regional localisation was replaced by region-specific
      structural health care information variables. During this analysis the regional
      frequency of medical specialists was significant at a 5% level (odds ratio: 1.07;
      95% confidence interval: 1.02-1.12). This result can be interpreted as an
      increase in surgical procedures by 7% for each additional specialist per 10,000
      persons. However, no definite conclusion can be reached based on the available
      data. Intensifying the presented survey-based health services research has the
      potential to identify regional over- or undersupply of medical services, to
      objectify and accompany informational, administrative or political action and
      thereby to support equity in access and health care in the sense of an optimized
      allocation of resources.

PMID- 10955003
TI  - [Sustainability and the relevance of poverty: an unresolvable contradiction? The
      example of the Evangelical Lutheran Church in Tanzania].
AB  - Public Health systems in developing countries are in a field of tension between
      two poles: sustainability and accessibility. A several months check on hospitals
      run by the Lutheran Church in Tanzania led us to conclude, however, that the
      great majority of these institutions have neither a survival chance nor have they
      made any substantial contribution to the status of public health care for the
      poor. Basing on the results of this check we discuss a few measures to transform
      church-run public health systems in developing countries in accordance with the
      goals of sustainability and accessibility. It is, however, evident that it will
      not be enough just to increase the technical efficiency of existing hospitals.
      What is needed--and this seems indeed to be the only feasible way--is to effect a
      complete reorganisation in the sense of Primary Health Care. It is only then that
      church-run Public Health Care may survive in these countries and that provision
      of adequate health care can be ensured for many patients.

PMID- 10955004
TI  - [Opinions and attitudes on the topic of vaccination of established physicians,
      pharmacists and their personnel and current vaccination status of these groups].
AB  - Object of this investigation was to evaluate attitudes and opinions of general
      practitioners, internal specialists and pharmacists with regard to vaccination.
      At the same time we investigated the actual vaccination state of these groups and
      of the medical staff and pharmacy staff. Physicians and pharmacists answered by
      using a four-page written questionnaire. The vaccination state was evaluated by a
      single-page questionnaire. Analyses were made by using the statistical program
      SPSS. The 161 physicians and 188 pharmacists participating in this study
      generally agree that the risk of infection in practice and pharmacy is not
      significant. The best vaccine protection in these groups was observed for
      tetanus. An effective inoculation against this pathogen was documented by 79.4%
      of physicians and 63.3% of pharmacists. 73.4% of physicians had also a protection
      against hepatitis B. All other vaccinations were documented as actually
      protective only in 6-55% of the cases. Physicians and pharmacists agree that
      their staff should have a vaccination against tetanus, diphtheria and
      poliomyelitis, followed by hepatitis B and influenza. The vaccination state of
      medical staff and pharmacy-staff does not attain the demanded standard. It shows
      levels of 3-70%. Further education in vaccination is more often practised by
      pharmacists and their staff than by physicians and medical staff. Physicians are
      more active in advising patients about vaccination than pharmacists and patients
      rather consult their doctor than a pharmacist to give them vaccination advice.
      There is still a need for motivation of physicians and pharmacists to be an
      example for their patients and clients respectively. In addition, more of public
      information could be helpful.

PMID- 10955005
TI  - [School entrance screening: prospects for health data collection for health
      promotion in the school and community].
AB  - The function of school entrance examinations changes over the period of history.
      Nowadays the early diagnosis of special disease is done by the medical
      practitioner outside the public health department, while the school health
      services are confronted with a new task in the field of local surveillance and
      health promotion. A doctorate thesis focuses on the question of what data should
      be obtained by the school entrance examination and what are the results for a
      data-based health promotion in school and community. The thesis concentrates on
      North Rhine-Westphalia and is based on an expert interview concerning to the
      "Jugendarztlichen Definitionen" of the Bielefelder Modell.

PMID- 10955007
TI  - [Smoking and periodontal health].
AB  - The causal agents of destructive periodontal disease are several gram-negative
      bacteria. The mere presence, however, in the dental biofilm does not guarantee
      onset of the disease. The immunological and inflammatory host response as well as
      connective tissue and bone metabolism are strongly influenced by genetic,
      acquired and behavioural risk factors. Among the last, tobacco consumption holds
      a primary position. Prevalence, extent and severity of periodontitis as well as
      tooth loss and edentulism are influenced by tobacco consumption in a dose
      dependent manner. About 50% of periodontal disease in young adults is
      attributable to cigarette smoking. Postoperative results in periodontally
      diseased smokers are considerably poorer than those achieved in non-smokers. As a
      consequence smoking cessation has to be in corporated in traditional treatment
      concepts for inflammatory periodontal disease.

PMID- 10955006
TI  - [Deficits in socioeconomic and psychosocial support of HIV-positive women].
AB  - Despite increasing numbers of heterosexually transmitted HIV-infected women and
      high numbers of female i.v.-drug users within HIV-infected population the subject
      of HIV-infection in women has been of low interest during the past years in
      Germany. This prospective study investigated the economic, social and
      psychological situation with regard to the special situation of this group. While
      there was no difference in clinical parameters we found a worse economic
      situation of HIV-positivity in women. Concerning the psychosocial situation there
      were few differences, but HIV-infected women sought help by voluntary workers
      more often. Specific education and socioeconomic support of HIV-infected women
      are conditions for the success of antiretroviral therapy of HIV-infection which
      has recently become more demanding and complex.

PMID- 10955008
TI  - [Global budget: topic of health structural reform--topic for public health].

PMID- 10955009
TI  - [Public health developments and potentials: the International Public Health
      Congress 1999 in Freiburg i. Br].
AB  - In October 1999 a big conference (about 1300 participants) on Public Health took
      place for the first time in Germany. The conference was aiming at giving a
      comprehensive survey of theory and practice of Public Health in German-speaking
      countries. Four main topics were identified in about 550 contributions
      (workshops, posters and oral presentations): health care research, health
      services research/health economics, prevention/health promotion and methods.
      Geographical and topical distribution of the contributions is presented.

PMID- 10955010
TI  - [Risk to patients by hepatitis B infected surgeons: health monitoring of medical
      personnel in hospitals must be evaluated].

PMID- 10955012
TI  - [Procedures in complementary medicine. Can they be taken seriously?].

PMID- 10955013
TI  - [7 questions about early summer meningoencephalitis. When is there a risk for
      residual damage?].

PMID- 10955011
TI  - [Are children during expert assessment for nursing care needs properly
      classified?].

PMID- 10955014
TI  - [Injury with infected needle. The surgical glove as a virus killer?. Interview by
      Annette Vorpahl].

PMID- 10955015
TI  - [Coronary heart disease prevention. Are there differences in cholesterol
      synthesis inhibitors?].
AB  - All statins have been shown to reduce plasma cholesterol concentrations
      significantly. Cardioprotective effects of these drugs appear to be mainly due to
      cholesterol lowering. It remains unclear whether pharmacokinetic differences of
      statins are of clinical relevance. The clinical studies with statins performed on
      more than 30,000 individuals demonstrate that lipid lowering drug therapy not
      only reduces cardiovascular complications but also is a safe and well tolerated
      long-term therapy. However, the majority of patients who should be treated
      according to appropriate guidelines, still do not receive any cholesterol
      lowering therapy. Therefore, it is a main goal that at least high-risk patients
      (e.g. with coronary heart disease or diabetes mellitus type 2) should be treated
      with statins.

PMID- 10955016
TI  - [Weight reduction, statins or fibrates? How to reach lipid goal values in
      diabetic patients].
AB  - Diabetics have a greatly increased risk for cardiovascular disease. At the center
      of the pathogenesis is the elevated blood sugar, insulin resistance and
      hyperinsulinemia. Treatment must therefore be aimed at controlling glucose
      metabolism (HBA1c < 7.0%) and lipid metabolism (LDL conc < 100 mg/dL,
      triglycerides < 150 mg/dL). Blood pressure should not exceed 130/85 mmHg. In
      addition to changes in lifestyle--low-fat, calorie-controlled diet and increased
      physical activity--lipid-lowering medication can rarely be done without. On the
      basis of the results of large interventional studies, the CSE inhibitors are
      particularly to be recommended. While the domain of the fibrates is the lowering
      of triglycerides, no comparative data on the usefulness of this group of
      substances are currently available.

PMID- 10955017
TI  - [When cholesterol lowering drugs should not be too expensive. Statins are
      especially effective in secondary prevention].

PMID- 10955018
TI  - [When the voice becomes weaker. Functional causes of dysphonias].

PMID- 10955019
TI  - [Diabetic foot syndrome. An interdisciplinary diagnostic and therapeutic
      challenge].

PMID- 10955020
TI  - [Diabetic foot syndrome series. 1. Basic diagnosis in general practice].

PMID- 10955021
TI  - [Diagnostic quiz. Jaundice with lymph node swelling. Cholestatic hepatitis in
      infectious mononucleosis].

PMID- 10955022
TI  - [Planned expansion of patient rights. That is absolutely unnecessary, claims a
      legal expert].

PMID- 10955023
TI  - [ACE inhibitor and calcium channel blocker in a fixed combination. Lowering blood
      pressure in diabetic patients].

PMID- 10955024
TI  - [Accomplishing 2 goals at once. Nephropathy and cardiac risk].

PMID- 10955025
TI  - [Osteoporosis-induced fractures. Bisphosphonates lower risk also in the hip].

PMID- 10955026
TI  - [Drug therapy of benign prostatic hyperplasia. Pumpkin et al. in the front line].

PMID- 10955027
TI  - [Women and double stress. Torn between family and career].

PMID- 10955028
TI  - [10. Differential diagnosis and therapy of anemia].

PMID- 10955029
TI  - Vascular anomalies.

PMID- 10955030
TI  - Mergerworld: a play in one act.

PMID- 10955031
TI  - Acute pulmonary edema with ST elevation.

PMID- 10955032
TI  - A medical clerk with chills, fever, and neck mass.

PMID- 10955033
TI  - Hematopoietic stem-cell transplantation from an unrelated donor.
AB  - When an HLA-matched sibling is not available and nontransplant approaches have
      been ineffective, transplantation of hematopoietic stem cells from an unrelated
      donor can effect a cure in some patients with chronic myelogenous leukemia. Even
      when successful, however, transplantation is a rigorous and prolonged process
      whose complications include infection and graft-versus-host disease. Improvements
      in hematopoietic stem-cell transplantation as well as innovative nontransplant
      approaches may improve the outcome in these patients.

PMID- 10955034
TI  - Current management of disseminated intravascular coagulation.
AB  - Both a bleeding and a thrombotic disorder, disseminated intravascular coagulation
      presents diagnostic and therapeutic challenges. At present, diagnosis requires a
      set of blood tests; therapy focuses on reversing the underlying disorder and
      providing supportive treatment. Clinical studies of specific tests and treatments
      are now under way.

PMID- 10955035
TI  - Should we hug our patients?

PMID- 10955036
TI  - A 20-year-old woman with jaundice.

PMID- 10955037
TI  - Management and prevention of meningococcal disease.
AB  - While many other illnesses affecting children have been contained or even
      eliminated, meningococcal disease has become a leading infectious cause of death.
      The major management challenge may be increased intracranial pressure or toxic
      shock, depending on whether meningitis or septicemia predominates. A new protein
      conjugated group C vaccine is expected to reduce deaths by as much as 40%.

PMID- 10955038
TI  - Active living: on the road with the 10,000 Steps program.

PMID- 10955039
TI  - Interaction of vitamin C and cigarette smoke.

PMID- 10955040
TI  - MNT essential to plans for adding prescription drug benefit to Medicare.

PMID- 10955041
TI  - One size does not fit all in obesity research.

PMID- 10955042
TI  - Dietary fat and the feeding relationship.

PMID- 10955044
TI  - Dietary guidelines and the Food Guide Pagoda. The Chinese Nutrition Society.

PMID- 10955043
TI  - How the Chinese link dietary advice to their national plan of action for
      nutrition.

PMID- 10955045
TI  - Update on the Minority Recruitment and Retention Research Project. American
      Dietetic Association Diversity Committee.

PMID- 10955046
TI  - Cognitive strategies for reporting portion sizes using dietary recall procedures.
AB  - OBJECTIVES: To examine recall strategies used by interview respondents when
      making judgments about portion size and to better understand how respondents use
      various portion-size aids. DESIGN: Study participants were separated into groups,
      each using a different set of portion-size estimation aids: (a) 2-dimensional
      paper aids presented in stacks, (b) 2-dimensional aids, cut out and presented on
      rings, (c) household-type aids, and (d) a combination of 2- and 3-dimensional
      aids, many of which are used in national government surveys. Respondents gave a
      "quick list" of foods consumed the previous day and practiced cognitive thinking
      skills. Then the interviewer selected at least 2 solid, 2 liquid, and 2 amorphous
      foods for probing. Respondents were asked to think aloud as they reported how
      much they ate of each food. Types and frequencies of cognitive strategies used
      for portion-size estimation were determined. SUBJECTS: Interviews of 1 to 1 1/2
      hours were conducted with 76 adults aged 18 to 65 years. Participants were
      recruited to obtain a mix of races, ages, educational levels, and genders.
      RESULTS: The most frequently used strategy was visualization and comparison to
      aids. Others strategies were known amounts, estimations based on known amounts,
      visualization of volume or a container, and actions such as pouring or moving
      hands to the mouth. Respondents preferred aids that were similar in size and
      shape to actual portions consumed for liquid or amorphous food and preferred the
      ruler for solid foods. APPLICATIONS: To obtain the best data from dietary
      recalls, expect answers that are possible for respondents to give, supply
      respondents with aids that help them recall amounts consumed, and guide
      respondents to appropriate aids that help them formulate focused responses.

PMID- 10955047
TI  - Defining and measuring stages of change for dietary behaviors: readiness to meet
      fruit, vegetable, and grain guidelines among Chinese Singaporeans.
AB  - OBJECTIVE: To assess the ability of 2 algorithms to classify people by stage of
      change for consuming the recommended servings of grains (cereal foods) and total
      fruit and vegetables. DESIGN: Assessment of stage involved an objective
      behavioral measure in the form of a self-administered food frequency
      questionnaire, followed by a brief telephone interview to assess intentions of
      subjects to increase intake to meet the recommended servings. Validity of the
      stage classification was assessed by comparison with three 24-hour dietary
      recalls. SUBJECTS: One hundred and one Singaporean Chinese subjects (mean age =
      38.7; 51% men) were recruited from 716 respondents who had taken part in a survey
      investigating factors influencing consumption of grains, fruit, and vegetables.
      STATISTICAL ANALYSES PERFORMED: Differences in mean intake by diet recalls across
      the stages were investigated using analysis of variance. Sensitivity,
      specificity, and predictive values of the algorithms were also determined.
      RESULTS: There were significant increases across the stages in mean intake of
      grains (men: F(2,48) = 20.30, P < .001; women: F(2,47) = 23.39, P < .0001), and
      total fruit and vegetables (men: F(2,48) = 30.29, P < .005; women: F(2,47) =
      37.29, P < .0001). Based on diet recalls for grains intake, the algorithms
      classified 89% of subjects having inadequate intakes into the preaction stages,
      and 75% of those having adequate intakes into the action or maintenance stages.
      For fruit and vegetables, 93% of subjects having inadequate intakes were
      classified into the preaction stages, and 76% of those having adequate intakes
      were classified into the action or maintenance stages. CONCLUSION: Algorithms
      developed to assess stages of change for food-based rather than nutrient goals,
      and which include an objective assessment of intake, appear to improve the
      accuracy of stage classifications.

PMID- 10955049
TI  - Prompting methods affect the accuracy of children's school lunch recalls.
AB  - OBJECTIVES: To evaluate the feasibility of implementing 3 specific prompting
      methods among students in the first and fourth grades (mean age = 7.2 and 10.1
      years, respectively), to validate recall accuracy of first- and fourth-grade
      students against observation, to develop a single measure of inaccuracy that
      cumulated errors in reporting food items and amounts without allowing
      underreporting and overreporting to cancel each other, and to establish
      information regarding the measure of inaccuracy for use in future studies.
      DESIGN: Children were interviewed the morning after they were observed eating
      lunch provided by the school. Interviews included free recall, nonsuggestive
      prompted recall, and specific prompted recall (either preference, food category,
      or visual). SUBJECTS/SETTING: Ninety-six children (48 students per grade) were
      studied--32 per the specific prompting method--stratified by grade, sex, and
      ethnicity (African-American or white). Specific prompting method was randomly
      assigned to children within strata. STATISTICAL ANALYSIS: Food items were
      categorized and weighted as: combination entree = 2, condiments = 1/3, and other
      = 1. To calculate inaccuracy of recall, absolute differences between amounts
      reported and observed eaten were calculated for each item and then multiplied by
      each item's weight; these values were then summed across all items for each
      child. Inaccuracy of recall was determined before specific prompting and after
      specific prompting and for the difference (inaccuracy after specific prompting
      minus inaccuracy before specific prompting). RESULTS: Before specific prompting,
      median inaccuracy was 2.7 servings for the 48 first-grade students and 1.7
      servings for the 48 fourth-grade students. The median difference in inaccuracy
      from before to after specific prompting was 0 for both grades. Specific prompting
      increased recall accuracy for 9 first-graders and 12 fourth-graders, but
      decreased recall accuracy for 21 first-graders and 7 fourth-graders, and did not
      change recall accuracy for 18 first-graders and 29 fourth-graders. Among children
      whose recall accuracy increased after specific prompting, 5 first-graders and 8
      fourth-graders received prompting for food category. APPLICATIONS/CONCLUSIONS:
      Among first-grade students, specific prompting (either preference, food category,
      or visual) may hurt more than help recall accuracy. Among fourth-grade students,
      prompting for food category yields small gains in recall accuracy with minimal
      losses. Validation studies are needed with larger sample sizes to determine
      prompting methods that produce more accurate dietary recalls from children of
      various socioeconomic status groups, other racial/ethnic groups, and at other
      meals.

PMID- 10955048
TI  - Relationships between vitamin and mineral supplement use, dietary intake, and
      dietary adequacy among adolescents.
AB  - OBJECTIVE: To examine patterns of supplement use among US adolescents and the
      relationship between supplement use and dietary intake and adequacy. DESIGN:
      Adolescents self-reported 2 days of food intake using the 24-hour recall method
      and supplement use during a personal interview conducted as part of the 1994
      Continuing Survey of Food Intakes of Individuals (CSFII). SUBJECTS: A national
      sample of 423 adolescents included in the 1994 CSFII survey. STATISTICAL
      ANALYSIS: chi 2 analysis was used to determine which demographic factors were
      significantly related to patterns of supplement use. Weighted percentages of
      adolescents by category of supplement use for selected vitamins and minerals
      (calcium; iron; zinc; folic acid; and vitamins A, B-6, C, and E) are presented.
      Relationships between dietary intake of macronutrients and vitamins and minerals
      among adolescents and supplement use were determined using a least-squares model
      of general linear regression. RESULTS: Approximately one-third of adolescents
      reported using supplements, with 15.6% of youth using them on a daily basis. The
      majority of supplement users reported taking multivitamins (N = 95; 65.5%)
      whereas only one-third of supplement users reported taking individual vitamins or
      minerals. Supplement use was found to vary by gender, household size, and US
      region of residence. Adolescents who reported using supplements had higher mean
      dietary intakes of most micronutrients and lower intakes of total and saturated
      fat than those who did not use supplements. More than one-third of adolescents
      had dietary intakes of vitamins A and E, calcium, and zinc that were < 75% of the
      US Recommended Dietary Allowance. APPLICATIONS/CONCLUSIONS: The majority of US
      adolescents do not use vitamin or mineral supplements. Interestingly, adolescents
      who do use supplements, even on an infrequent basis, consume diets that are more
      nutrient-dense than those who do not use supplements. Dietary intakes of several
      micronutrients were inadequate among all adolescents in this study, regardless of
      supplement use status. There is a need to develop and implement programs aimed at
      improving the dietary intakes of US adolescents.

PMID- 10955050
TI  - Food-safety educational goals for dietetics and hospitality students.
AB  - OBJECTIVE: To identify food-safety educational goals for dietetics and
      hospitality management students. DESIGN: Written questionnaires were used to
      identify educational goals and the most important food safety competencies for
      entry-level dietitians and foodservice managers. SUBJECTS: The sample included
      all directors of didactic programs in dietetics approved by the American Dietetic
      Association and baccalaureate-degree hospitality programs with membership in the
      Council on Hotel, Restaurant, and Institutional Education. Fifty-one percent of
      the directors responded. STATISTICAL ANALYSIS: Descriptive statistics were
      calculated. chi 2 analysis and independent t tests were used to compare
      educators' responses for discrete and continuous variables, respectively.
      Exploratory factor analysis grouped statements about food safety competence.
      Internal consistency of factors was measured using Cronbach alpha. RESULTS:
      Thirty-four percent of dietetics programs and 70% of hospitality programs
      required or offered food safety certification. Dietetics educators reported
      multiple courses with food safety information, whereas hospitality educators
      identified 1 or 2 courses. In general, the educators rated food-safety
      competencies as very important or essential. Concepts related to Hazard Analysis
      and Critical Control Points (HAACP), irradiation, and pasteurization were rated
      less highly, compared with other items. Competencies related to reasons for
      outbreaks of foodborne illness were rated as most important.
      APPLICATIONS/CONCLUSIONS: Food safety certification of dietitians and an
      increased emphasis on HAACP at the undergraduate level or during the practice
      component are suggested. Research is recommended to assess the level of food
      safety competence expected by employers of entry-level dietitians and foodservice
      managers.

PMID- 10955051
TI  - Provision of nutrition counseling, referrals to registered dietitians, and
      sources of nutrition information among practicing chiropractors in the United
      States.
AB  - OBJECTIVE: To investigate US chiropractors' provision of nutrition counseling and
      referrals to registered dietitians and sources of nutrition information.
      Chiropractors' perceptions of the minimum educational requirement for registered
      dietitians and nutrition training received in chiropractic school were also
      examined. DESIGN: A descriptive study was conducted by use of a nationwide,
      mailed survey. SUBJECTS/SETTING: Surveys were sent to 1,590 practicing
      chiropractors in the United States, selected randomly from The National Directory
      of Chiropractic. Of the 410 responses received, 375 were usable (response rate =
      23.6%). STATISTICAL ANALYSIS: Descriptive statistics were used to summarize data
      along with the Pearson chi 2 test and Kendall tc rank correlation to determine
      associations for categorical questions. RESULT: Nearly 90% of respondents
      provided nutrition counseling to their patients, even though the majority
      believed that they were inadequately trained in nutrition. One-on-one dietary
      instruction was the most common method of providing nutrition counseling, and
      supplement use was the most common health-related situation/condition for which
      nutrition counseling was used. Most respondents did not correctly select the
      minimum educational requirement for registered dietitians, did not refer patients
      to registered dietitians, and did not use registered dietitians as a source of
      nutrition information. Nevertheless, 65% of respondents anticipated increased
      collaborations between registered dietitians and chiropractors.
      APPLICATIONS/CONCLUSIONS: Chiropractors provide nutrition counseling to a large
      number of patients each year; thus, they have the potential to substantially
      affect patients' nutritional status. There is a clear need and opportunity for
      registered dietitians to collaborate with chiropractors.

PMID- 10955052
TI  - Use of qualitative methods to study diet, acculturation, and health in Chinese
      American women.
AB  - Improving the health status of minority populations in the United States is a
      major public health challenge. This report describes an anthropological approach
      to obtaining information needed for designing and evaluating a culturally
      appropriate dietary intervention for Chinese-Americans. Ninety-minute qualitative
      interviews were conducted with 30 less-acculturated Chinese-American women in
      their native language (Cantonese or Mandarin), soliciting information from
      participants regarding usual food consumption; knowledge, attitude, and beliefs
      about diet and disease; and factors that influence food choices. Interviews were
      recorded, translated, transcribed, and coded for themes. Two focus groups with 6
      participants each were conducted to cross-validate the interview findings. Among
      our participants, breakfast was usually the first meal to be "Westernized,"
      largely for reasons of convenience. Food quality, cost, and availability were
      some of the most important predictors of dietary change after immigration to the
      United States. Respondents said that there was a strong connection between diet
      and disease. However, they were not familiar with US dietary guidelines, food
      labels, or other sources of dietary information, but reported that friends and
      Chinese newspapers were their primary source of nutrition information. We used
      these findings to develop quantitative dietary survey instruments adapted for
      Chinese-Americans. This type of qualitative groundwork is an important precursor
      to the design, implementation, and evaluation of dietary interventions for
      minorities.

PMID- 10955053
TI  - Chronic radiation enteritis: women's food tolerances after radiation treatment
      for gynecologic cancer.

PMID- 10955054
TI  - Estimating energy contributed by fiber using a general factor of 2 vs 4 kcal/g.

PMID- 10955055
TI  - Nutrition concerns and food-safety concerns occur independently among adults.

PMID- 10955056
TI  - Older adult women find food preparation easier with specialized kitchen tools.

PMID- 10955057
TI  - Influence of food choices on high school students' perception of school
      foodservice.

PMID- 10955058
TI  - Case problem: dietary recommendations to combat obesity, insulin resistance, and
      other concerns related to polycystic ovary syndrome.

PMID- 10955059
TI  - Minority recruitment and retention in dietetics: issues and interventions.
AB  - To better understand the reasons why minorities and males are underrepresented
      among registered dietitians (RDs) and dietetic technicians, registered, (DTRs)
      and to develop focuses for intervention, the investigators performed a telephone
      survey of newly credentialed RDs and DTRs and directors of RD and DTR education
      programs. Using lists of students recruited by the American Dietetic Association
      for participation in the survey, the investigators interviewed 83 RDs and DTRs
      and 20 education program directors. RDs and DTRs attributed minority
      underrepresentation primarily to the field's lack of visibility and
      underrepresentation of men to the traditional association with women. Education
      program directors attributed minority underrepresentation to educational
      disadvantages, particularly in scientific subjects. Findings from this study
      support program-level interventions such as increasing program flexibility,
      initiating outreach to K-12 schools and lower-division college students,
      providing tutoring in a nondemeaning atmosphere, and visibly expressing
      commitment to minority representation. More fundamental changes in the profession
      itself appear necessary for large-scale increases in minority representation.
      These include increasing internship opportunities; raising the profession's level
      of remuneration, prestige, and independence; increasing scholarship support; and
      advertising nationally through channels capable of reaching minorities.

PMID- 10955060
TI  - Developing community-based strategies to decrease maternal morbidity and
      mortality due to unsafe abortion: pre-intervention report.

PMID- 10955061
TI  - [Retroperitoneal sarcoma. Treatment of 51 patients].
AB  - Soft tissue sarcomas are exceedingly rare, making up less than 1% of all solid
      malignancies. In the retroperitoneum, they tend to be large when diagnosed and
      are a therapeutic challenge to the surgical oncologist. Our experience with 51
      patients with retroperitoneal sarcomas operated on during the past 4 years is
      presented. 37 were primary and 26 presented as recurrent tumors. The group
      included many different histological subtypes, the majority being high grade
      tumors. Complete resection was achieved in 84%, necessitating extensive surgery,
      but was not possible in 8 patients (16%) who underwent partial resection or
      biopsy only. There was 1 perioperative fatality (2%). 18 (35%) suffered
      complications, all of which were reversible. The estimated 5-year survival in the
      complete resection group is 40%, while none of those who underwent partial
      resection survived more than 2 years. There was significantly better survival in
      patients with primary, low grade sarcomas which were smaller than 8 cm, compared
      to those with high-grade, recurrent sarcomas larger than 8 cm. Local recurrence
      developed in 8 patients of the complete resection group (18%), 2 months to 3
      years after surgery. These data show that despite the concept of retroperitoneal
      sarcomas as being aggressive, invasive tumors with a poor prognosis, the
      prognosis is not unusually bad. With proper surgical technique, resectability may
      be high, with improved overall survival.

PMID- 10955062
TI  - [Pelvic floor exercise and biofeedback in women with urinary stress
      incontinence].
AB  - Stress urinary incontinence is a medical and social problem. In the past decade
      there has been increased awareness of this condition and the number of those
      affected who seek help is increasing. Treatment is usually surgical-elevation of
      the bladder neck. Pelvic floor exercise is an accepted conservative treatment
      modality used for mild to moderate cases who have not yet completed their
      families. We present our results in 30 women, aged 28-71 years, av. 49% with
      genuine stress incontinence treated with pelvic floor exercise and biofeedback.
      14 patients (46.7%) were completely cured and 15 (50%) were improved. In only 1
      was there no improvement. Our results show significant improvement in the
      duration and intensity of pelvic floor contractions after treatment. Pelvic floor
      exercise with biofeedback is a very important treatment modality, requiring a
      highly motivated patient and a physiotherapist specialized in pelvic floor
      exercise.

PMID- 10955063
TI  - [Attention deficit disorder: attentional characteristics of developmental right
      hemisphere syndrome].
AB  - Developmental right hemisphere syndrome (DRHS) is characterized by emotional and
      interpersonal difficulties, attention deficit hyperactivity disorder (ADHD),
      visuo-spatial handicaps, subtle left body neurologic signs and failure in
      nonverbal academic domains, especially arithmetic. Concurrence of ADHD and DRHS
      is not surprising because research has implicated dysfunction of the right
      hemisphere in both syndromes. Furthermore, the right hemisphere has more brain
      areas devoted to attentional processing, making it more important and more
      vulnerable in attentional problems. We describe the clinical parameters of DRHS
      as exemplified by 2 cases, a boy and a girl, both 13 years old. They participated
      in a study group in which attention and speed of performance were assessed in
      children with DRHS and were compared to children with ADHD and to a control
      group. A tendency to overfocusing, difficulty in inhibition, perseverative
      behaviors, stereotypy, and slowness and absence of hyperactivity characterized
      the DRHS group. These behaviors led us to hypothesize that the attentional
      symptoms in DRHS define a specific subgroup of ADHD which requires a different
      therapeutic approach.

PMID- 10955064
TI  - [High alkaline phosphatase in subacute thyroiditis].
AB  - Subacute thyroiditis may be hard to diagnose, therefore patients are sometimes
      misdiagnosed and subjected to unnecessary work-up. We report a 37-year-old man
      with subacute thyroiditis and a high concentration of serum alkaline phosphatase.
      After aspirin treatment there was clinical improvement and decrease in rapid ESR,
      and in high serum thyroxin and alkaline phosphatase. The increased alkaline
      phosphatase, seen in as many as 50% of patients, is of hepatic origin, and is not
      caused by high serum thyroxin. Awareness of this relationship may help in
      diagnosis and may prevent unnecessary diagnostic procedures, which may be
      invasive.

PMID- 10955065
TI  - [Laparoscopic spermatic vein ligation: first experience in the treatment for
      varicocele in adolescents].
AB  - We report our initial experience with laparoscopic ligation of spermatic veins in
      the treatment of varicocele in adolescence. 19 boys, 13 to 18 years old,
      underwent this treatment between I 1997 and III 98. The varicocele was always on
      the left side. 12 complained of scrotal discomfort and pain, but in 7 it was
      found incidentally during routine medical examination by the family or school
      physician. The diagnosis was based only on physical examination. There has been
      no morbidity related to the laparoscopic procedure and all returned to normal
      activity within a few days. Follow-up 2-12 months after surgery showed no
      varicocele in any. We conclude that laparoscopy is useful in the treatment of
      varicocele in adolescents.

PMID- 10955066
TI  - [Laparoscopy for common bile duct stones].
AB  - We performed 75 laparoscopic cholecystectomies during July and September 1996. In
      3 men and 4 women, aged 32-87 years, there was obstructive jaundice caused by
      choledocholithiasis. During laparoscopy in the jaundiced patients, calculi were
      identified by cholangioscopy and intra-operative cholangiography. They were
      washed into the duodenum (confirmed cholangiographically) after intravenous
      glucagon injections and dilation of the papilla of Vater. Serum bilirubin and
      liver enzyme levels returned to normal within a few days. There was no operative
      or postoperative morbidity, nor any biliary-related systemic complications.
      Average postoperative hospitalization was 3 days.

PMID- 10955067
TI  - [Management of pancreatic trauma in damage-control laparotomy].
AB  - Major pancreatic trauma challenges the trauma surgeon with diagnostic problems
      and choices of treatment modalities. The most important determinant guiding
      management is the integrity of the main pancreatic duct. The preoperative and
      intraoperative assessment and treatment of pancreatic injury may be difficult,
      especially when concurrent severe injuries are present. There are alternative
      approaches in the management of the traumatized pancreas when ductal injury is
      not obvious during initial exploratory laparotomy.

PMID- 10955068
TI  - [Intrahospital transport of critically ill children].
AB  - Prospective evaluation of intrahospital transportation of 33 critically ill
      children to and from the pediatric intensive care unit was conducted over the
      course of a month. Factors contributing to risk of transport were assessed. There
      were 33 children (25 boys and 8 girls), 3 days to 15 years of age. Reasons for
      admission included: disease and trauma in 19, and status post operation in 11.
      The pretransport PRISM score was 4.84. 22 children (66.6%) were being
      mechanically ventilated and 10 (30.3%) were being treated with amines. Transport
      time ranged from 8-150 minutes. 15 of the transports (45.4%) were urgent and a
      special intensive care team escorted 22 (66.6%). Equipment mishaps and
      physiological deterioration occurred in 12 (36.3%) and 11 (30.3%) of the cases,
      respectively. The use of amines, mechanical ventilation, longer transport time
      and high PRISM score were all associated with physiological deterioration on
      transport.

PMID- 10955070
TI  - [Malthus and his work--its past and present effect].

PMID- 10955069
TI  - [Fatal rat bites].
AB  - We present a rare case of infant death due to blood loss resulting from multiple
      rat bites. Domestic dogs and cats cause most animal bites. Bites of a house rat
      usually cause bacterial infection, successfully treated with antibiotics. There
      is little information about death due to house rat bites. Since the wounds they
      cause tend to occur post-mortem, they are usually wedged, clean and without
      subcutaneous bleeding. An 11-week-old, malnourished infant girl was bitten to
      death while sleeping in her mother's bed in a rat-infested home. The infant's
      clothing was covered with blood, parts of her face were missing and marks of
      gnawing were present on her neck and extremities. There was subcutaneous bleeding
      around the wounds indicating that they were inflicted while the child was alive.
      Autopsy findings revealed profound blood loss. We conclude that a combination of
      low socio-economic status, severe failure to thrive, and poor hygiene in a rat
      infested environment contributed to the fatal outcome in this attack.

PMID- 10955071
TI  - [Microchimera--the secret path that leads to autoimmunity?].

PMID- 10955072
TI  - [Cholesterol oxidation, macrophage foam cells and atherosclerosis: importance of
      antioxidants and paraoxonase].

PMID- 10955073
TI  - [Sudden nocturnal death syndrome].

PMID- 10955074
TI  - [BCG in the treatment of superficial transitional cell carcinoma of the urinary
      bladder].

PMID- 10955075
TI  - [Conservative treatment of adenocarcinoma of the endometrium in young patients:
      has its time arrived?].

PMID- 10955076
TI  - [Penicillin allergy: an update. III: Cross reactivity between beta-lactam drugs].

PMID- 10955077
TI  - [Elevated serum levels of creatine kinase in acute psychotic patients].

PMID- 10955078
TI  - [Epidemiology and control of head lice in Israel].

PMID- 10955079
TI  - [Absorbable mesh wrapping of injured kidney: a renal salvage technique].
AB  - Blunt trauma to the kidney is a rare cause of hospitalization, found in only 3%
      of patients hospitalized for trauma. Surgery is seldom required, but if necessary
      there are a variety of surgical techniques to preserve renal function. Organ
      wrapping with absorbable mesh is a procedure previously described, but renal
      wrapping has not gained the same acceptance as splenic or hepatic wrapping. We
      describe a 30-year-old man with grade III blunt renal trauma, in whom this
      technique was applied. He was discharged after 10 days without complications.

PMID- 10955080
TI  - [Surprising conclusion of Sennacherib's campaign to conquer Jerusalem, 701 BC].

PMID- 10955081
TI  - [Samuel Kristeller: the man and the maneuver].

PMID- 10955082
TI  - [1000 cardiac catheterizations in congenital heart disease].
AB  - Over the past 15 years, percutaneous therapeutic cardiac catheterization has
      become increasingly important in the treatment of congenital heart disease. We
      describe our experience in 1000 such catheterizations between 1993-1997. 55% were
      in 1-12-year-olds; only 20% were in patients younger than 1 year old and 11.3%
      were in adults with congenital heart defects. In about 50% it was at least a
      second cardiac catheterization. Overall, there were 425 therapeutic cardiac
      catheterizations, increasing from 33% in the first 200 procedures, to 63% in the
      last 200. We performed 30 different types of therapeutic catheterizations: 23.3%
      were valvular dilations, 21.4% vessel angioplasties, 36.9% closure procedures,
      9.2% electrophysiological procedures, and 9.2% miscellaneous. In 31.3% of
      therapeutic catheterizations we used 12 new procedures. Minor complications
      occurred in 8.5% and major in 0.6%; most complications were successfully treated
      or were self-limited and there was no residual damage. In this report the current
      role of each type of major catheterization is discussed on the basis of our
      experience. Further development of technology for lesions not amenable to
      currently available transcatheter methods, and longer follow-up for current
      techniques will consolidate the role of therapeutic cardiac catheterization in
      congenital heart disease.

PMID- 10955083
TI  - [Monocytic ehrlichiosis--an emerging zoonotic disease in Israel].
AB  - Ehrlichiosis is an emerging zoonotic disease transmitted to man by ticks. Its
      clinical features include fever, headache, myalgia, nausea and rash. The
      diagnosis requires a high index of suspicion; the disease has a specific
      serology, and has never been reported in Israel. We describe a 52-year-old man
      hospitalized with fever, a diffuse rash, arthralgia and epididymitis. Skin biopsy
      disclosed necrotizing small vessel disease consistent with periarteritis nodosa.
      Acute phase serum titer for E. chaffeensis was 1:256. Fever promptly subsided
      following ciprofloxacin.

PMID- 10955084
TI  - [Information provided in writing for "informed consent" in clinical trials].
AB  - The Helsinki Declaration contains recommendations guiding physicians who conduct
      clinical trials. One is that the requirement for informed consent is essential
      for approval of a trial. An important component of the informed consent doctrine
      is that all data required for the participant's decision must be provided. We
      analyze data of a therapeutic trial, and define 12 data components outlined in,
      or directly derived from the Helsinki Declaration. 61 instances of informed
      consent for therapeutic clinical trials from various fields of medicine, from
      1994 to 1997, were analyzed. In each the presence of the 12 components was
      evaluated. The data demonstrated that there were only 5 components cited in most
      cases of informed consent: trial objectives, methods, treatment plan, risks, and
      the option of withdrawing. Benefit to the participant was mentioned in half the
      cases, while only limited information was provided about other components such as
      life-threatening and unpredictable risks, and alternative treatment. Examples of
      informed consent from 1997 showed statistical improvement since 1994 in the data
      concerning trial objectives, methods, risks and alternative therapy. Informed
      consent documents of international multicenter trials compared with local trials
      showed statistical improvement in the data components of the trial objectives,
      methods, and risks, including those of potentially life-threatening and
      unpredictable risks, and alternative therapy. Analysis of informed consent showed
      that not all components required for a comprehensive decision regarding
      participation in a clinical trial are included. These data emphasize the need to
      design a structured informed consent protocol in which all the required data
      components are specifically outlined for potential participants.

PMID- 10955085
TI  - [Abdominal trauma in childhood--the conservative approach in 95 cases].
AB  - To determine the results of the conservative approach in the treatment of
      pediatric abdominal trauma, we retrospectively analyzed data from the files of 95
      cases of abdominal trauma in children during a 5-year period. 51 patients (54%)
      had isolated abdominal injury, while 44 (46%) had multiple trauma. The most
      common causes of injury were road accidents and falls from heights (74%). CT
      scans were performed in 61 (64%) with positive results in 90%. Ultrasonography
      was done in 22 (23%) and was positive in 55%. The spleen was the most vulnerable
      intra-abdominal organ (33 patients, 35%), as well as the organ most severely
      damaged. Other injured organs were: liver (30 cases), kidney (16), stomach (2),
      large blood vessels (2), and pancreas, duodenum and diaphragm (1 case each). 83
      patients (87%) were treated conservatively, while 11 were operated on for
      penetrating abdominal trauma (3 cases), hemodynamic instability (3), positive DPL
      (3), and Scale 4 splenic injury and free intra-abdominal air on CT scan (1 case
      each). Early and late complications were mild. It is concluded that CT is an
      efficient and reliable imaging method for diagnosis and staging of severity of
      injury in blunt abdominal trauma. Nonoperative management of solid organ injuries
      under careful observation in a pediatric trauma center is safe and appropriate.
      Most Scale 4 splenic injuries can be treated successfully without surgical
      intervention. Using this conservative approach there were no late complications.

PMID- 10955087
TI  - [Laparoscopic treatment of small bowel obstruction caused by adhesions].
AB  - We describe our experience in 14 patients operated on for small bowel
      obstruction, who underwent laparoscopic adhesiolysis. In 13 (93%) the obstruction
      was relieved and only 1 case required conversion to open operation. Bowel
      activity usually resumed within 24-48 hours, and there were no remarkable
      intraoperative and postoperative complications. During follow-up none developed
      recurrent obstruction. Our experience demonstrates that laparoscopic adhesiolysis
      is a valid therapeutic option. Additional experience is needed to determine which
      types of cases are suitable for the procedure.

PMID- 10955088
TI  - [Malignant nodular hidradenoma--sweat gland tumor].
AB  - Malignant hidradenoma is a very rare tumor that originates from sweat glands. We
      present a 61-year-old man with an ulcerated tumor in his right flank, 4 cm in
      diameter, that was excised with a wide free margin. Histopathologic study showed
      an ill-defined, epithelial neoformation, formed by lobules of clear polygonal
      cells in the deep dermis and subcutaneous tissue, diagnosed as malignant nodular
      hidradenoma. 1.5 years after excision there was enlargement of the right axillary
      and inguinal lymph nodes, which showed metastatic, adnexal neoplastic cells.
      Axillary resection and superficial dissection of the right inguinal nodes were
      performed. After 3 months the tumor had spread to other lymph nodes and acute
      obstructive renal failure required insertion of a pig-tail catheter into the
      right ureter. Radiotherapy was followed by chemotherapy, but he died from end
      stage metastatic disease in multi-organ failure.

PMID- 10955086
TI  - [Head injuries in children--clinical characteristics as prognostic factors].
AB  - An unselected series of 200 consecutive cases of major head trauma in children
      aged 6 months to 16 years, seen during 4 years, was studied. Injuries were due to
      road accidents (40%), falls (30.5%) and other causes (29.5%), and were assessed
      clinically and by cranial CT. On admission the Glasgow Coma Score ranged from
      4.72-11.65 and in addition to pupillary responses and brain stem reflexes, was a
      significant predictor of outcome. Brain edema, midline shift, intracranial
      hemorrhage and also hyperglycemia, hypokalemia and coagulopathy, were associated
      with poor outcome. While 17% died, 53% were discharged in good functional
      condition. Early identification of clinical features related to prognosis can
      help the caring team provide maximal support for patient and family.

PMID- 10955090
TI  - [Pitfalls and skewing on impact factor calculations--may we use them for
      evaluation of scientific quality?].

PMID- 10955089
TI  - [Polyneuropathy in critical illness].
AB  - Critical illness polyneuropathy developed in 8 patients aged 22-84 years in our
      intensive care units. This acute polyneuropathy, predominantly axonal and motor,
      develops in the setting of the systemic inflammatory response syndrome and multi
      organ failure. It is found in about 50% of patients treated in intensive care
      units for more than 2 weeks. In those who survive, neurological and functional
      recovery is the rule.

PMID- 10955091
TI  - [Sensible use of placebo in psychopharmacological research].

PMID- 10955092
TI  - [Use of computers in medicine: special application to intensive care].

PMID- 10955093
TI  - [The microlaparoscope--a new instrument for minimal access surgery under local
      anesthesia].

PMID- 10955094
TI  - [Fixation of fractures by bioabsorbable implants].

PMID- 10955096
TI  - [Listeria monocytogenes--the bacterium, mode of transmission and relation to food
      consumption].

PMID- 10955095
TI  - [Low-intensity anticoagulant treatment--indications and efficacy].

PMID- 10955097
TI  - [Anagrelide--a new drug to reduce platelets in myeloproliferative diseases].

PMID- 10955098
TI  - [Update on diagnosis of limb girdle muscular dystrophy].

PMID- 10955099
TI  - [Malnutrition and growth retardation in children and adolescents with Crohn's
      disease].

PMID- 10955100
TI  - [Juvenile diabetes--who is afraid of physical activity?].

PMID- 10955101
TI  - [Cognitive symptoms as consequences of closed head injury].

PMID- 10955103
TI  - [Medicine in Jerusalem during the Ayyubid period].

PMID- 10955102
TI  - [Smoking alcoholics--are smoking cessation programs adequate in the framework of
      alcoholism treatment?].

PMID- 10955104
TI  - [Ludwig Wilhelm Mauthner (1806-1858): founder of the first children's hospital in
      Austria].

PMID- 10955105
TI  - [The many "faces" of congenital duodenal obstruction].

PMID- 10955106
TI  - [Home palliative care of terminal cancer patients with family feedback: from the
      experience of the decision to continue the community care service in the North].
AB  - Palliative care of terminal cancer patients is one of the tasks of our Home Care
      Unit. Increasing hospitalization costs have brought forward the decision to treat
      them at home, assuming that they would prefer to return and die in their natural
      surroundings, among family. Most of our patients are aged, recent immigrants from
      the Soviet Union, of low socioeconomic status; most live with their close
      families. Our care model combines social, cultural, economic, medical and nursing
      aspects. More patients choose to die at home, and that is where costs are
      minimal. Care management and characteristics of 44 terminal cancer patients, who
      died between January and October 1996, are described. Living with a family was
      not required for treatment at home. Length of care by the unit ranged from 1-48
      weeks, with an average of 8.5 and a median of 6. 55% of patients were
      hospitalized, most (58%) for 5-9 days for noncancerous diseases, and then
      discharged home. 54% died at home, a third were hospitalized for 2-17 days before
      death. Compared to the average length of stay in palliative care oncology wards,
      1044 days and more than NIS 500,000 were saved. A telephone survey examined
      families' satisfaction with various components of care. 92% were satisfied with
      the home treatment. 79%-82% felt that the nurse and doctor of the team met their
      needs and expectations. Half the families were satisfied with the treatment of
      pain. Families in which treatment was 24 weeks or more were generally less
      satisfied than those with shorter treatment at home. We learned that an early
      entry into treatment is necessary; hospital referral criteria should consider to
      a greater extent the coping ability of families; nursing aid hours should be
      increased and professional emotional support added; additional pain control
      methods should be used. All these would strengthen families, improve quality of
      care, and contribute to additional savings by decreasing hospital stay.

PMID- 10955107
TI  - [Perinatal co-infection with hepatitis B and HIV viruses--reciprocal effect of
      the disease and the treatment].
AB  - We report the case study of a 1-year-old girl who was perinatally infected with
      both hepatitis B (HBV) and HIV viruses. The clinical presentation and treatment
      are described. We examined the interaction between the 2 viruses and the possible
      effects of the interaction on the development of each virus and on treatment. Our
      findings demonstrate that combined HIV and HBV infections intensified
      deterioration, as the HBV liver disease aggravated the HIV infection. The
      medication of choice was Lamivudine, since it prevents the transcription of both
      viruses.

PMID- 10955108
TI  - [Depression scale for research in and identification of postpartum depression].
AB  - Postpartum depression (PPD) is a relatively frequent and serious condition, with
      negative consequences for the mother, her infant, and the family. From research
      and clinical experience in many countries, it has been found that PPD can be
      identified early, and women at risk for developing PPD can be identified before
      delivery in the framework of primary health care service. The Edinburgh Postnatal
      Depression Scale (EPDS) has been found valid for this purpose, both in the
      original English version, and in translation to numerous languages. The Hebrew
      translation of the EPDS is presented, and it is recommended that Israeli
      researchers use the same translation to facilitate accumulation of knowledge
      regarding the epidemiology of PPD and intervention strategies in various Israeli
      population groups, and for comparison with data from other countries.

PMID- 10955109
TI  - [Angiotensin converting enzyme (ACE) gene polymorphism in a diabetic cohort and
      diabetic nephropathy].
AB  - The renin-angiotensin system is thought to play an important role in the
      pathophysiology of kidney disease in diabetes. Previous studies have shown a
      possible association between the D allele of the angiotensin converting enzyme
      (ACE) gene, known to be associated with higher circulating levels of ACE, and
      increased risk of developing nephropathy in NIDDM. The present study investigated
      the distribution of ACE gene genotypes in the general population and patients
      with NIDDM, the association between the D allele and diabetic nephropathy, and
      the association between the ACE genotype and involvement of other target organs
      in NIDDM. The ACE genotype (insertion/deletion I/D) was determined in all
      subjects, subsequently divided into 3 groups based on their polymorphism (DD, DI
      and II). The presence of nephropathy was defined by an albumin-creatinine ratio
      of 30 mg/g or greater (mean of 2 first morning urine samples). In the general
      population most had the D allele (DD or ID) and a minority the II genotype. There
      was no association between genotype and hypertension, ischemic heart disease,
      hyperlipidemia, and cerebrovascular or peripheral vascular disease. In diabetics
      the genotype distribution was not different from that in the general population.
      Within the diabetic group, there was no association between genotype and
      hypertension, hyperlipidemia, duration of diabetes, or HbA1C levels. Nephropathy,
      found in 81 of the 156 with NIDDM, was not associated with genotype. Diabetic
      nephropathy was not associated with retinopathy, neuropathy, or ischemic heart,
      cerebrovascular or peripheral vascular disease. We conclude that in the
      population sampled, there was no association between the D allele of the ACE gene
      and the risk of developing nephropathy in NIDDM.

PMID- 10955110
TI  - [Effect of specific inspiratory muscle training on dyspnea and exercise tolerance
      in congestive heart failure].
AB  - It has been shown that the inspiratory muscles of patients with congestive heart
      failure (CHF) are weaker than normal. This weakness may contribute to dyspnea and
      limit exercise capacity. But respiratory muscles can be trained for increase in
      both strength and endurance. This study was designed to evaluate the effect of
      specific inspiratory muscle training (SIMT) on muscular performance, lung
      function, dyspnea and exercise capacity in moderate heart failure. 10 patients
      with CHF (NYHA functional class II-III) received 1/2 hour of SIMT daily, 6
      times/week, for 3 months. They started breathing at a resistance 15% of their
      Pimax for 1 week and the resistance was then increased incrementally to 60%.
      Spirometry, inspiratory muscle strength and endurance, and the 12-minute walk
      test were performed before and after the training period. All showed an increase
      in inspiratory muscle strength and endurance. This was associated with a small
      but significant increase in FVC, a significant increase in the distance walked
      (458 +/- 29 to 562 +/- 32 m, p < 0.01), and improvement in the dyspnea index
      score. SIMT resulted in increased inspiratory muscle strength and endurance. This
      increase was associated with decreased dyspnea and an increase in submaximal
      exercise capacity. SIMT may prove to be useful complementary therapy in CHF.

PMID- 10955111
TI  - [Accidental severance of a venous catheter: diagnostic and therapeutic approach].
AB  - The most common invasive procedure performed in hospitals is the insertion of a
      vascular access device. This procedure has the rare complication of catheter
      emboli. Accidental cutting of a peripheral catheter, the use of duplex ultrasound
      to locate the cut and the extraction of the catheter through a venesection is
      described. If peripheral extraction fails, percutaneous extraction or thoracotomy
      should be tried, in that order. The immediate precautions have an impact on the
      final results.

PMID- 10955112
TI  - [Combined sclerotherapy and surgery for huge cervical lymphangioma].
AB  - Lymphangioma is a benign developmental anomaly of the lymphatic system located in
      about 40% of cases in the neck and usually completely resectable. In some cases
      it invades adjacent structures such as the larynx, pharynx, or tongue. In such
      cases it is almost impossible to resect completely, as this would endanger vital
      structures. We describe a baby born with a huge cervical lymphangioma which
      invaded the tongue, larynx, pharynx and other cervical structures. He was treated
      with bleomycin and aethoxysklerol. The sclerotherapy shrank the lymphangioma
      considerably and it became resectable. At 2 years of age the cosmetic result is
      good and vital function, such as swallowing and facial expression, are preserved.

PMID- 10955113
TI  - [The "new age"--epidemiological aspects].

PMID- 10955114
TI  - [Atherosclerosis as a chronic inflammation].

PMID- 10955115
TI  - [Diseases caused by Clostridium neurotoxins, and immunological approaches to
      treatment and prevention].

PMID- 10955116
TI  - [Molecular mechanisms underlying the neuromuscular toxicity of Clostridium
      toxins].

PMID- 10955117
TI  - [Spontaneous pregnancies in young women following premature ovarian failure].

PMID- 10955119
TI  - [Prenatal diagnosis of trisomy 18].

PMID- 10955118
TI  - [Current therapies of genital herpes simplex in women].

PMID- 10955120
TI  - [Uterine papillary serous carcinoma--a different kind of tumor].

PMID- 10955121
TI  - [Computerized test as a diagnostic auxiliary--TOVA--another tool in the diagnosis
      off attention deficit disorders (ADHD)].

PMID- 10955122
TI  - [Rupture of the tendon of the long head of the biceps in the arm: approach to
      treatment in athletes].

PMID- 10955123
TI  - [Determining power factors of clinical departments in a medical center].
AB  - The intradepartmental power factors in a medical center were studied. 3 strategic
      contingency factors were examined, based on the model of Hickson et al. (1971):
      centrality, substitutability, and coping-with uncertainty. Only coping-with
      uncertainty contributed directly to departmental power, and not the summation of
      the 3. Power derives from department resources, connections and influence outside
      the medical center. Aspects related to inpatient treatment or teaching of
      residents did not contribute directly to departmental power status. Power is
      gained in stages: in the first the department contributes to the factor of
      centrality (mainly patient treatment, teaching and research). In the middle
      stage, power is gained due to the factor of substitutability--the unique services
      and research which the department has developed. The third stage contributes
      directly to power-coping with uncertainty. This implies the ability of a
      department to solve crucial problems of the medical center. Surprisingly, the
      clinical field (i.e. surgery) did not contribute significantly to power. The
      current trend is toward empowering ambulatory units in the medical center.

PMID- 10955124
TI  - [Prevalence of APO e4 allele in Israeli ethnic groups].
AB  - The 4 allele of the APOE gene, coding for apo-lipoprotein E, is the most common
      genetic risk factor for Alzheimer's disease and a significant risk factor for
      coronary atherosclerosis. There is therefore much interest in studying its
      frequency in different ethnic groups. We examined its frequency in Jews
      originating from Libya, Buchara and Ethiopia and in Jews of Sepharadi and
      Ashkenazi origins. Its frequency among Ethiopian immigrants was 0.27,
      significantly higher than in the other groups, in which the frequency was between
      0.067 and 0.10. These differences in allele frequency may serve as a basis for
      future studies in Israel to assess the relative contributions of genetic and
      environmental factors to the incidence of dementia.

PMID- 10955125
TI  - [First experiences with retroperitoneoscopic lumbar sympathectomy].
AB  - We present our initial experience with retroperitoneoscopic lumbar sympathectomy
      in a series of 5 men aged 25-45 years. 3 suffered from ischemia of the lower
      limbs due to Buerger's disease, 1 had severe reflex sympathetic dystrophy and 1
      had vasculitis with severe, non-healing lower leg ulcers. The right
      retroperitoneal space was developed with a dissecting balloon-trocar introduced
      via a small lateral muscle-splitting flank incision. 2 additional 5 mm trocars
      were used for instrumentation and clipping. L2-L3 or L3-L4 ganglia were resected;
      mean operating time was 120 minutes. Only oral analgesics were needed for
      postoperative pain control and oral food intake was resumed the following
      morning. The procedure was successful in all and was without complications. Mean
      hospital stay was 2 days. All patients reported significant relief of ischemia or
      dystrophic pain and/or improvement in trophic changes in the extremities. In the
      patient with leg ulcers, the largest was successfully covered with a skin graft.
      The retroperitoneoscopic approach to lumbar sympathectomy successfully combines
      the advantages of minimal invasive surgery and the reliability and effectiveness
      of well-established open sympathectomy.

PMID- 10955126
TI  - [Relapse of sarcoidosis after alternative medical treatment].
AB  - Reference to alternative medicine frequently appears in newspaper headlines,
      advertisements and in articles in medical journals. The practice of alternative
      medicine has increased, even as the number of critical articles warning of
      deleterious effects have also increased. Public demand is strong and growing, but
      there are no clear rules as to what is not permissible, particularly when
      treatment is not by qualified physicians. There are still no clear indications
      and contraindications for complementary (not alternative) medicine in patients
      with organic injuries and life-threatening conditions. However, it is obvious
      that in these patients complementary medicine should not be substituted for
      conventional therapy. We present a 32-year-old man with sarcoidosis who
      discontinued conventional therapy on his own initiative and began alternative
      medicine (homeopathy) with subsequent deterioration in his condition. He was
      hospitalized for a relapse of his sarcoidosis which required large doses of
      corticosteroids.

PMID- 10955127
TI  - [Pregnancy outcome in fetuses with increased nuchal translucency thickness at 10
      14 weeks of pregnancy].
AB  - Increased thickness of fetal nuchal translucency (TNT) measured at 10-14 weeks of
      gestation, may suggest underlying fetal chromosomal defects, structural
      abnormalities or genetic syndromes. We examined the relationship between
      increased TNT and pregnancy outcome, especially in fetuses with normal
      karyotypes. 1400 pregnant women underwent first trimester scanning and screening
      for chromosomal abnormalities and measurement of fetal TNT. 25 fetuses (2%) with
      increased TNT (> 3 mm) were identified. 8 (30%) had an abnormal karyotype. Of
      these, 5 pregnancies were aborted, 3 ended in spontaneous abortions before
      karyotyping, and 2 were terminated, all before detailed cardiac scanning. There
      was a high association between increased TNT and karyotype abnormalities. The
      total incidence of favorable outcome in fetuses with normal chromosomal and
      cardiac features but enlarged TNT was 56%.

PMID- 10955128
TI  - [Superficial skin necrosis--an uncommon manifestation of short bowel syndrome].
AB  - Short bowel syndrome causes a complex of symptoms due to compromise of small
      intestinal nutrient absorption. A 60-year-old woman underwent major resection of
      the small intestine due to a road accident 3 years ago. The sole manifestation of
      short-bowel-syndrome was superficial skin necrosis due to vitamin K deficiency.
      She was asymptomatic for a long time, until treatment with antibiotics further
      intensified initially subclinical malabsorption. It is not clear why there had
      been no other symptoms and why the main impact was on the fibrinolytic system
      rather than the coagulation system, as is usually the case. It is recommended
      that patients after major resection of the small intestine be closely monitored
      for coagulation function if an oral antibiotic is prescribed.

PMID- 10955129
TI  - [Propafenone dose for emergency room conversion of paroxysmal atrial
      fibrillation].
AB  - Paroxysmal atrial fibrillation (AF), a frequent cause of repeated
      hospitalization, is effectively treated with propafenone. The time to conversion
      to sinus rhythm is a consideration when managing AF in the emergency room. We
      investigated the conversion rates of paroxysmal AF by 3 different oral
      propafenone (P) regimens, in terms of time to conversion. 188 patients with onset
      of AF within 48 hours were treated with propafenone (P): 48 received 600 mg as a
      first oral dose followed after 8 hrs by 150 mg (Group A); 82 received 300 mg as a
      first dose, followed by the same dose 3 and again 8 hrs later (B); 58 received
      150 mg every 3 hrs, up to a total dose of 600 mg (C). P was stopped when sinus
      rhythm was achieved. Rates of conversion to sinus rhythm after 3 hrs in the 3
      groups were: 46%, 41% and 26% respectively; after 8 hrs: 77%, 78% and 70%; and
      after 12 hrs: 81%, 84% and 76%. Treatment was discontinued in 8. There was
      excessive QRS widening (> 25% of the basal value) in 1 in group A, 1 in group B
      and 2 in group C; wide-QRS tachycardia occurred in 4 in group B. In Group A there
      was a higher rate of early successful conversion, with a lower incidence of side
      effects than with the other regimens.

PMID- 10955130
TI  - [Sacral insufficiency fractures and low back pain in elderly women].
AB  - Sudden low back pain is common in elderly women. It causes physical and mental
      stress, and results in deterioration of functional movement and in activities of
      daily living. Awareness of possible sacral insufficiency fracture is important;
      they may be demonstrated by imaging modalities, mainly radionuclide bone scan.
      Prognosis is good and accurate diagnosis serves to exclude malignancy and relieve
      fear of chronic pain and disability. We describe 4 women, aged 84, 82, 71 and 77
      who illustrating the clinical and imaging findings of this disorder.

PMID- 10955131
TI  - [The clinical pharmacist in internal medicine--impact on the quality of
      therapeutic care].
AB  - Several studies have documented the impact of clinical pharmacy services on
      patient care and drug costs in hospital wards. However most hospitals in Israel
      do not provide such services and until recently their benefits in local health
      care have not been demonstrated. We therefore determined whether the activity of
      a pharmacist in the medical department of a medical center leads to improved
      quality of drug utilization and reduced costs. During the first 3 months of the
      clinical pharmacist's work all interventions and consultation were documented.
      The effect of these interventions on drug costs was calculated by the change in
      drug acquisition costs during the study period compared with those of preceding
      months, as well as in the other 5 medical departments of the hospital without
      clinical pharmacy services. During the study period the pharmacist joined 44
      clinical rounds in which he documented 40 consultations in response to
      physicians' requests for drug information and 42 interventions on his own
      initiative. The pharmacist's recommendations were accepted in 38 of the 42 cases
      (90%). In 10 cases the pharmacist's initiative in improving the quality of drug
      therapy led to an increase in drug acquisition costs. However, the overall drug
      costs during the study period decreased 12.6%. During the same period drug costs
      in the other medical departments decreased only 2.2%. The results of this study
      conform with those of many other studies that show a beneficial impact of the
      clinical pharmacist on the quality of drug therapy and on drug costs. They
      indicate that the clinical pharmacist can play a crucial role in the medical
      department.

PMID- 10955132
TI  - [New tools for better staging of colorectal cancer--therapeutic applications].

PMID- 10955134
TI  - [Home hospitalization: why is it developing, and what is its place in the health
      care system?].

PMID- 10955133
TI  - [Cancer and antibodies to p53].

PMID- 10955135
TI  - [Contraception in emergencies].

PMID- 10955136
TI  - [Radiotherapy for the treatment of choroidal neovascularization secondary to age
      related macular degeneration].

PMID- 10955137
TI  - [Myocutaneous island flaps for pelvic pressure sores].

PMID- 10955138
TI  - [Cerebral palsy and multiple pregnancy].

PMID- 10955139
TI  - [Leukotriene modifiers: the role in the treatment of childhood asthma].

PMID- 10955140
TI  - [Is it possible to promote fracture repair? Review of biological methods to
      accelerate fracture repair].

PMID- 10955141
TI  - [Management of delirium in the elderly].

PMID- 10955142
TI  - [Breast feeding and the neonatal immune system].

PMID- 10955143
TI  - [Sarcopenia--personal approach].

PMID- 10955144
TI  - [Speech disorder in Biblical times--Moses: "a heavy mouth and a heavy tongue"].

PMID- 10955145
TI  - [Left lung atelectasis due to tooth in the left bronchus].

PMID- 10955146
TI  - [Laparoscopic donor nephrectomy: initial experience in Israel].
AB  - We present our initial experience in laparoscopic nephrectomy. 6 patients were
      operated for a kidney donation and 2 for treatment of a benign disease. All
      procedures were completed successfully, with no conversion to laparotomy or
      intraoperative complications. Mean operating time was 210 minutes, and in the
      donor kidneys the mean warm-ischemic time was 165 seconds. There were 3
      postoperative complications, and mean hospitalization was 3.5 days. The
      transplanted kidneys are all functioning. From our initial experience,
      laparoscopic nephrectomy appears to be both feasible and safe. Its implementation
      requires a combined team with experience in donor surgery and advanced
      laparoscopic skills. The procedure may increase the availability of living donor
      kidneys, due to the smaller impact on the donor compared to conventional donor
      nephrectomy.

PMID- 10955147
TI  - [Nephron-sparing surgery--initial experience with 50 patients].
AB  - During recent years the use of the new imaging techniques, ultrasonography and
      computerized tomography, has increased. The accessibility to these methods has
      changed the pattern of detection of renal lesions. Over 90% of renal masses are
      now discovered incidentally, while investigating nonurological symptoms.
      Therefore, most lesions are discovered in their early stages. The gold-standard
      procedure for removing renal masses is radical nephrectomy, which ensures
      complete removal of an organ-confined lesion, but involves loss of functional
      tissue. This might be critical in patients with a single kidney, or reduced
      nephron function. There are several diseases characterized by multiple renal
      lesions, such as Von Hippel-Lindau and tuberous sclerosis in which radical
      treatment may lead to chronic dialysis in young patients. Nephron-sparing surgery
      was developed in order to preserve as much functional tissue as possible while
      removing safely any suspicious renal lesion. This new technique, not involving
      radical surgery, should be evaluated in cases of renal tumors for its ability to
      achieve the same cancer cures rates. We present our experience with our first 50
      patients who underwent nephron-sparing surgery for removal of renal lesions.

PMID- 10955148
TI  - [Adjuvant therapy of colon cancer stage C MAC. Adverse effects and efficacy in
      the Department of Oncology, Soroka Medical Center in the years 1991-1994].
AB  - The National Institutes of Health (NIH) held a consensus conference which
      recommended 5-FU and levamisole as adjuvant chemotherapy for colon cancer MAC
      (Modified Astler Coller) stage C. From 1991-1994, 37 such patients diagnosed here
      were treated with 5-FU (intravenous dose of 450/mg/m2/d for 5 days and from day
      29, once a week for 48 weeks) and oral levamisole (50 mg 3 times/d. for 3 days,
      every 2 weeks for a year), as suggested by NIH guidelines. 16 patients were males
      and 21 were females, mean age was 62 years and median 64. Cancer locations were:
      right colon (in 16, 43%), left colon (19, 51%), multiple colon primaries (2, 1%).
      25 (68%) had 1-3 positive lymph nodes and 12 (32%) had 4 or more positive lymph
      nodes. Only 20 (54%) finished treatment as prescribed. In the others, 1 or both
      drugs caused side-effects for which the drugs had to be stopped. 6 patients
      relapsed while on treatment. The most common side-effects were diarrhea,
      stomatitis and bone marrow suppression. 3 were hospitalized due to neutropenic
      fever. 5-year actuarial survival of all patients was 61%; 5-year relapse-free
      survival was 61%; 5-year relapse-free survival of right versus left colon was 41%
      and 82%, respectively (p < 0.01). There was no significant difference in 5-year
      survival of those with 1-3 positive lymph nodes as compared to those with 4 or
      more (62% and 56%, respectively). 5-year survival in those who finished or did
      not finish treatment (excluding those who stopped treatment because of
      progressive disease) was 83% and 70%, respectively (NS). The 5-year survival of
      our series was similar to that of patients treated similarly elsewhere. The 5-FU
      and levamisole treatment was not tolerated well by our study population. It has
      recently been replaced in our service by a 5-FU and leucovorin regimen given for
      6 months.

PMID- 10955149
TI  - [Pediatric research in an office-setting network--a new dimension in pediatric
      research in Israel].
AB  - Pediatric care in the community is gradually replacing traditional care in
      hospitals. Despite that, research activity in the community setting is minimal
      due to objective difficulties. These are mainly constraints of time, office work
      and lack of research-supporting logistics. In the past decade, throughout the
      world, primary physicians interested in research have grouped together and formed
      research networks. The aim of such networks is to support and promote research in
      the community. An Israel Pediatric Research in Office-Setting network (IPROS) was
      established 2 years ago by the Israel Ambulatory Pediatric Association (IAPA).
      Today, there are over 140 pediatricians listed in IPROS, representing the
      heterogeneous composition of pediatricians in Israel. The network's policy is
      defined by a joint steering committee. The committee is composed of IAPA
      representatives, senior network members and Schneider Hospital senior
      investigators. The research subjects are diverse, and represent common practical
      issues. Effective intra-net communication is vital to the existence of the
      network, and is accomplished by 3 modalities: 1) semiannual updates by mail, 2) e
      mail, using an electronic mailing list to facilitate connection between members,
      3) semi-annual meetings. Research budgets are derived from public sources like
      the Ministry of Health and IAPA, and private sources such as pharmaceutical
      companies. The administration of the network is supported by Schneider Children's
      Medical Center, and financed by IAPA.

PMID- 10955150
TI  - [Rehospitalization of children].
AB  - The aims of the study were to determine the rate of rehospitalization in 1997 a
      month after the end of initial hospitalization. 72 of 1174 children (6.1%) were
      rehospitalized. The mean age was 4.6 +/- 3.6 years (range 1 month-16 years). The
      average duration of the initial hospitalization of the 72 children was 8.3 +/-
      6.0 (range 1-50) days, but only 3.6 days for all hospitalized children. The
      duration of the rehospitalization was 4.1 +/- 2.1 days (range 1-10 days), the
      interval between the 2 hospitalizations was 11.1 +/- 9.6 days (range 1-30 days).
      Among the diseases of the rehospitalized children in decreasing order were:
      respiratory diseases (including ORL) (40.9%), gastrointestinal diseases (27.7%),
      nervous system diseases, and bacteremia and septicemia (5.6%). Second
      hospitalizations in connection with these conditions were: gastrointestinal
      disease (34.7%); respiratory disease (29%); and bacteremia and septicemia
      (11.1%). Our recommendations are for attending physicians to follow-up regularly
      and periodically children who suffer from chronic diseases and are prone to
      develop exacerbations. This should be done in cooperation with hospital
      specialists so that the cooperation may reduce the rehospitalization of these
      children.

PMID- 10955151
TI  - [Comprehensive geriatric assessment--its clinical, social and economic importance
      and prospects].
AB  - It is well known that many elderly patients are referred to nursing homes because
      of "functional decline" without being thoroughly investigated. We studied 9
      elderly patients, all referred to hospital due to functional decline and
      diagnosed as follows: spinal stenosis--2 cases, depression--3, thyrotoxicosis--1,
      Parkinson--1, polypharmacy and congestive heart failure--1 patient each. Proper
      diagnosis and appropriate treatment prevent unnecessary hospitalization in
      nursing homes. Our study is meant to draw attention to this crucial aspect of
      geriatric medicine.

PMID- 10955152
TI  - [Many faces of parvovirus].
AB  - 2 women, aged 31 and 37 years, respectively, suffered from acute febrile illness
      due to acute infection with human parvovirus B19. 1 also had a maculopapular rash
      and articular symptoms after her fever stopped, a clinical picture typical of
      erythema infections. The other had leukopenia and thrombocytopenia and had
      received dipyrone. Although acute infection with human parvovirus usually occurs
      in childhood, it may also occur in adults, with protean manifestations.

PMID- 10955153
TI  - [Acute, painful, swollen testis in polyarteritis nodosa: a diagnostic problem].
AB  - An acutely painful and swollen testis mandates urgent diagnostic and therapeutic
      measures since this symptom complex may indicate torsion of the testis. Prompt
      scrotal exploration is necessary if the testis is to be saved from ischemic
      necrosis. Polyarteritis nodosa (PAN) is a vasculitis involving mainly medium and
      small sized arteries and may damage any organ. In PAN, the presentation of an
      acutely painful and swollen testis raises a perplexing diagnostic problem since
      the symptoms may be related to vasculitis involving the testis on the one hand,
      or represent primary testicular pathology unrelated to the underlying PAN. A 31
      year-old man with PAN who presented with acute pain and swelling in a solitary
      testis is reported.

PMID- 10955154
TI  - [Severe psychiatric disorders during trips to the Far East].
AB  - 8 cases of acute mental disorders among Israelis travelling in the Far East are
      presented. The most common symptoms were hallucinations, paranoid delusions,
      agitation and depression. The important precipitating factors were drug abuse,
      reaction to the foreign environment and malarial prophylaxis. Treatment included
      creating a nonhostile environment, the presence of a Hebrew-speaking physician,
      psychopharmacotherapy and prompt evacuation to Israel. Most patients improved
      markedly and returned to normal functioning.

PMID- 10955156
TI  - [Ovulation induction and ovarian cancer: is there a link?].

PMID- 10955155
TI  - [New therapeutic modalities in Crohn's disease].

PMID- 10955157
TI  - [Diagnostic and clinical significance of fetal cells in maternal blood
      circulation].

PMID- 10955158
TI  - [Cystic echinococcosis, an endemic disease in Israel--updated diagnosis and
      treatment].

PMID- 10955159
TI  - [The cyclin family and its role in the development of cancer].

PMID- 10955160
TI  - [Diatoms and the diagnosis of drowning].

PMID- 10955161
TI  - [When should one suspect reflux disease as the trigger for asthma?].

PMID- 10955162
TI  - [Obesity in children: recent advances and recommendations for treatment].

PMID- 10955163
TI  - [Mechanisms of articular cartilage repair--research trends and clinical
      applications].

PMID- 10955164
TI  - [Do sun screens protect or damage the skin?].

PMID- 10955165
TI  - [Evaluation of psychiatric disability--conceptual and clinical classification].

PMID- 10955166
TI  - [Who needs the rotavirus vaccine?].

PMID- 10955167
TI  - [Caution: hemorrhoidal prolapse].

PMID- 10955168
TI  - [Severe mental disorders--need to reduce punishment for murder?].

PMID- 10955169
TI  - Talking about sexual matters with patients. Time to re-examine the CMPA's policy.

PMID- 10955170
TI  - Challenge of electronic medical records.

PMID- 10955171
TI  - Olanzapine: keep an eye on this neuroleptic.

PMID- 10955172
TI  - Caffeine during pregnancy? Correction.

PMID- 10955173
TI  - Controversies in antenatal corticosteroid treatment.
AB  - QUESTION: I am following up a former preterm infant, born at 29 weeks' gestation
      after premature labour. This infant had a relatively benign hospital course and
      when discharged was not thought to have any complications of prematurity. Despite
      this, at 1 year old his neurologic examination is abnormal: head circumference is
      on the 3rd percentile for age (weight on the 25th percentile), and he has
      increased tone in his lower legs and a moderate developmental delay. His
      discharge letter indicated that he was exposed antenatally to many doses of
      dexamethasone. Could this have adversely influenced his neurologic outcome?
      ANSWER: Antenatal steroids are proven therapy for preventing respiratory distress
      syndrome and decrease both morbidity and mortality associated with prematurity.
      Use of multiple doses of antenatal steroids might adversely affect neurologic
      outcome. There is insufficient evidence to support routine use of multiple doses
      of antenatal steroids when delivery of a preterm infant is anticipated.

PMID- 10955174
TI  - Dermacase. Multiple glomangiomas.

PMID- 10955175
TI  - Managing lower urinary tract infections. What is the best approach?

PMID- 10955176
TI  - Practice tips. Novel uses for nitroglycerin.

PMID- 10955177
TI  - What tests for suspected myocardial infarction? Serum cardiac troponin I or
      creatine kinase?

PMID- 10955178
TI  - Raloxifene. Not better than estrogen.
AB  - Raloxifene is marketed in France for prevention of nontraumatic vertebral
      fracture in postmenopausal women. In animal pharmacology studies, it was found to
      both agonize and antagonize estrogen. The assessment file is methodologically
      sound but fails to answer many practical questions. A placebo-controlled trial
      showed that raloxifene reduced the risk of vertebral collapse after 2 years of
      treatment, in both primary and secondary prevention, but demonstrated no effect
      on nonvertebral fractures. In this trial, raloxifene also reduced the risk of
      breast cancer. Two trials versus combined hormone replacement therapy (HRT)
      showed HRT had a more favourable effect on surrogate end points reflecting the
      risk of fracture and cardiovascular risk (changes in bone mineral density and
      lipid profile). Compared with combined HRT, raloxifene reduced the incidence of
      menorrhagia and mastodynia, but did not relieve symptoms linked to menopause.
      Results of animal studies call for close clinical monitoring to detect a possible
      increase in the incidence of ovarian cancer.

PMID- 10955179
TI  - Is hyperemesis gravidarum related to country of origin? Short report.

PMID- 10955180
TI  - Lifestyle health risk assessment. Do recently trained family physicians do it
      better?
AB  - OBJECTIVE: To determine whether recently trained family physicians were more
      likely to routinely assess lifestyle health risks during general medical
      evaluations. To document physicians' perceptions of the difficulties of lifestyle
      risk assessment, of medical training in that area, and of how often they saw
      patients with lifestyle health risks. DESIGN: Anonymous mailed survey conducted
      in 1995. SETTING: Family practices in the province of Quebec. PARTICIPANTS:
      Stratified random sample of 805 active family physicians of 1111 surveyed; 25
      were ineligible or could not be located, and 281 did not respond (74.1% response
      rate). MAIN OUTCOME MEASURES: Proportion of physicians graduating before and
      after 1989 who reported routinely (with 90% or more of their patients) assessing
      their adult and adolescent patients during general medical evaluations for
      substance use, sexual risk behaviours, and history of family violence and sexual
      abuse. RESULTS: Except for asking about drug use, recently trained family
      physicians did not report better assessment of lifestyle health risks during
      general medical examinations than family physicians who graduated more than 10
      years ago did. In both groups, routine assessment averaged 82% for tobacco use,
      68% for alcohol consumption, and 20% to 40% for sexual risk behaviours. Screening
      for family violence and sexual abuse was rare, but more frequently reported by
      older women physicians. Only 20% to 40% of recent graduates rated their medical
      training adequate for evaluating illicit drug use, family violence, and sexual
      abuse. CONCLUSION: Recently trained family physicians do not assess most
      lifestyle risk factors any better than their more experienced colleagues.

PMID- 10955181
TI  - Recent advances in management of genital herpes.
AB  - OBJECTIVE: To provide an update on new diagnostic tests and antiviral strategies
      for managing genital herpes. QUALITY OF EVIDENCE: Treatment guidelines are based
      on randomized clinical trials and recommendations from the Expert Working Group
      on Canadian Guidelines for Sexually Transmitted Diseases. Recommendations
      concerning other aspects of managing genital herpes (e.g., indications for using
      type-specific serologic tests) are mainly based on expert opinion. MAIN MESSAGE:
      Genital herpes is one of the most common sexually transmitted diseases, affecting
      about 20% of sexually active people; up to 80% of cases are undiagnosed. Because
      of frequent atypical presentation and the emotional burden associated with
      genital herpes, clinical diagnosis should be confirmed by viral culture. Type
      specific serologic assays are now available, but their use is often restricted to
      special situations and requires adequate counseling. New antivirals (valacyclovir
      and famciclovir) with improved pharmacokinetic profiles have now been approved
      for episodic treatment of recurrences and suppressive therapy. CONCLUSION: Wise
      use of new diagnostic assays for herpes simplex coupled with more convenient
      treatment regimens should provide better management of patients with genital
      herpes.

PMID- 10955182
TI  - Case report: sexual intercourse as potential treatment for intractable hiccups.

PMID- 10955183
TI  - Preparing patients to travel abroad safely. Part 4: Reducing risk of accidents,
      diarrhea, and sexually transmitted diseases.
AB  - OBJECTIVE: To present evidence-based recommendations on traveling abroad safely
      so family physicians can advise travelers on how to reduce risk of accidents,
      diarrhea, and sexually transmitted diseases (STDs) and how to treat diarrhea
      themselves if medical care is unavailable. QUALITY OF EVIDENCE: A MEDLINE search
      from 1990 to November 1998 found 163 articles on travel and accidents, 504 on
      travel and diarrhea, and 42 on travel and STDs. Titles and abstracts were
      reviewed, and randomized controlled trials (RCTs) and systematic reviews were
      sought. The Cochrane Collaboration database of systematic reviews and meta
      analyses was searched for studies relevant to family physicians. MAIN MESSAGE:
      For preventing diarrhea, RCTs demonstrate that bismuth subsalicylate,
      doxycycline, ciprofloxacin, and trimethoprim-sulfamethoxazole are useful
      prophylactics. Once travelers have diarrhea, RCTs show that loperamide and
      zaldaride reduce symptoms and duration; quinolones, ciprofloxacin, norfloxacin,
      and oral aztreonam reduce abdominal symptoms and time to last liquid stool by
      several days; azithromycin is effective in treatment of ciprofloxacin-resistant
      Campylobacter, and trimethoprim-sulfamethoxazole is effective in treating
      cyclospora. There are no RCTs of preventing accidents and STDs abroad. Health
      Canada has issued a statement summarizing the risks of acquiring STDs abroad.
      CONCLUSION: Family physicians can advise their patients on how to reduce risk of
      travelers' diarrhea and how to treat it themselves on holiday. There is expert
      advice on how to reduce risk of STDs.

PMID- 10955184
TI  - Adolescent health outreach program.

PMID- 10955185
TI  - Understanding acne: one man's journey.

PMID- 10955186
TI  - Acneiform eruptions.

PMID- 10955187
TI  - What's eating you? Rhipicephalus ticks.

PMID- 10955188
TI  - Drug therapies and adjunctive uses of alphahydroxy and polyhydroxy acids.

PMID- 10955189
TI  - A localized form of Darier's disease.
AB  - We report the case of a 33-year-old woman who presented with skin manifestations
      that resulted in a differential diagnosis of either an epidermal nevus or a
      localized form of Darier's disease. We discuss the arguments for and against each
      possibility. The available data on localized forms of Darier's disease are also
      discussed.

PMID- 10955190
TI  - Photo quiz. Fibrous histiocytoma.

PMID- 10955191
TI  - Sporadic congenital leukonychia with partial phenotype expression.
AB  - GOAL: To describe the characteristics and inheritance pattern of a case of
      congenital leukonychia. OBJECTIVES: 1. To describe the etiologies of congenital
      and acquired leukonychia. 2. To discuss the differential diagnosis of
      leukonychia. 3. To outline inheritance patterns associated with leukonychia.

PMID- 10955192
TI  - Ecthyma gangrenosum in patients with acquired immunodeficiency syndrome.
AB  - GOAL: To describe the reoccurrence of ecthyma gangrenosum (EG) in two patients
      with acquired immunodeficiency syndromes (AIDS). OBJECTIVES: 1. To describe the
      clinical characteristics of EG. 2. To discuss causative organism and risk factor
      for EG in patients with AIDS. 3. To identify rates of relapse/recurrence of EG in
      patients with AIDS.

PMID- 10955193
TI  - Rosacea 2000.

PMID- 10955194
TI  - Diltiazem-induced drug eruption sparing seborrheic keratoses.
AB  - A case of a diltiazem-induced morbilliform drug eruption, which spared the
      circumferential margin of seborrheic keratoses, is presented. Hypotheses
      regarding the pathogenesis of this novel exanthem are discussed. The potential
      mechanisms may be immunologic involving cytokines, or due to diminished levels of
      prostaglandin E2, altered optical properties of the skin, mechanical pressure
      phenomena, or altered local vasoconstriction secondary to diltiazem itself.

PMID- 10955195
TI  - Erythema ab igne following heating/cooling blanket use in the intensive care
      unit.
AB  - Erythema ab igne caused by chronic heat exposure presents as a net-like
      hyperpigmentation of the skin. We report this condition rapidly evolving due to
      the inadvertent use or dysfunction of an adjustable-temperature blanket in the
      intensive care unit. The use of heating/cooling blankets, especially in a patient
      with altered mental status, can result in iatrogenic erythema ab igne.

PMID- 10955196
TI  - Mutilating facial acne conglobata.
AB  - Acne conglobata, a severe form of acne vulgaris, often produces pronounced
      disfigurement. We describe a 23-year-old man with acne conglobata. Although this
      type of acne is often more marked on the back rather than on the face, our
      patient was unusual in that it was localized mainly to the cheeks. Conventional
      medical therapy was ineffective, or contraindicated. Radical surgical excision
      with subtotal removal of cheek skin and subcutaneous tissue was performed with an
      excellent result.

PMID- 10955197
TI  - Olanzapine is effective in the management of some self-induced dermatoses: three
      case reports.
AB  - Self-inflicted dermatoses are often difficult to treat. We present three patients
      with excoriated acne, self-induced skin ulcers, and trichotillomania,
      respectively, whose symptoms responded favorably to a 2- to 4-week course of the
      atypical antipsychotic olanazpine at a dosage of 2.5 to 5.0 mg daily. In two of
      three patients, the efficacy of the olanzapine was most likely related to an
      attenuation of dissociative symptoms that were associated with the self-induced
      skin ulcers and trichotillomania.

PMID- 10955198
TI  - Treatment of rosacea with doxycycline monohydrate.
AB  - Rosacea is one of the most commonly occurring inflammatory dermatoses treated by
      dermatologists today. Estimates suggest that at least 13 million Americans have
      recognized rosacea, and the clinical experience of most practitioners would add
      considerably more to that number. Rosacea is an inflammatory condition of the
      skin, classically presenting with a history of flushing and/or blushing along
      with the clinical findings of erythema, edema, telangiectasia, papules, pustules,
      and nodules of the face. Severity and distribution vary considerably. A patient
      may have only a few scattered papules and pustules of the central third of the
      face or there may be numerous inflammatory, painful, tender, large nodules. In
      some cases, only the face may be affected. In other cases, there may be lesions
      of the scalp, neck, and/or torso. Although the exact etiology is unknown, rosacea
      is thought by most experts to be an inflammatory process incited by vascular
      instability with subsequent leakage of fluid and inflammatory mediators into the
      dermis.

PMID- 10955199
TI  - A comparative evaluation of tretinoin gel microsphere, 0.1%, versus tretinoin
      cream, 0.025%, in reducing facial shine.
AB  - Tretinoin gel microsphere, 0.1%, is a highly effective anti-acne medication
      formulated with sponge-like microspheres encapsulating the active ingredient,
      tretinoin. In addition to minimizing cutaneous irritation, this system may also
      reduce facial shine. This single-center, double-blind, half-face study evaluated
      the potential of tretinoin gel microsphere, 0.1%, to reduce the appearance of
      facial shine compared to tretinoin cream, 0.025%. Thirty-five subjects (ages 12
      to 24 years) with moderate acne vulgaris and moderate facial oiliness, were
      evaluated after 4 consecutive days of product use. On sides treated with
      tretinoin gel microsphere, 0.1%, investigators found significantly reduced facial
      shine at 3 and 6 hours posttreatment. Subjects' self-evaluations revealed a
      significant reduction in facial shine at 3 hours posttreatment. Photographic
      analyses showed reductions in facial shine for both treatments, but decreases
      were greater on tretinoin gel microsphere, 0.1%-treated sides. Both therapies
      were well tolerated, and no adverse events occurred. Tretinoin gel microsphere,
      0.1%, has the added benefit of reducing the appearance of facial shine, which is
      a frequent concern in acne patients.

PMID- 10955201
TI  - Executive processing and attention deficit hyperactivity disorder: an application
      of the supervisory attentional system.
AB  - Children with attention deficit hyperactivity disorder (ADHD) display many
      behaviors consistent with an underlying deficit in executive processes. This
      study examines Norman and Shallice's (1986) supervisory attentional system (SAS)
      as an approximation of executive functioning thought to be impaired in ADHD.
      Fifteen ADHD children were compared to a clinical control sample of learning
      disabled (LD) children and control children matched for age, gender, and IQ on a
      series of tasks designed to tap the functions of the SAS. The tasks assessed
      either the inhibition of a strongly triggered response (Star Counting Test,
      Hayling Sentence Completion Test, and the Random Generation Test) or impulsive
      responding in the absence of strong trigger-schema contingencies (Brixton Spatial
      Anticipation Test). Analyses revealed that the ADHD group was significantly
      impaired, in comparison to the LD and control groups, on tasks requiring the
      inhibition of a strongly triggered response. Further support for the
      fractionation of the SAS is provided by the differential performance of the
      groups on these tasks.

PMID- 10955200
TI  - Developmental instability and working memory ability in children: a magnetic
      resonance spectroscopy investigation.
AB  - This study of children (ages 7 through 12) wishes to determine (a) whether
      variation in frontal lobe brain chemistry, determined from proton magnetic
      resonance spectroscopy (1H-MRS), is related to performance on a working memory
      task in children, and (b) whether developmental instability (DI; the imprecise
      expression of the genetic plan for development due to several known genetic and
      environmental effects) underlies phenotypic variation in brain chemistry. 1H-MRS
      assessed neurometabolites in a right frontal white matter voxel. The Visual Two
      Back test assessed working memory. A composite measure of DI was created from
      measures of minor physical anomalies, fluctuating asymmetry of body
      characteristics, and fluctuating asymmetry of dermatoglyphic features. Greater DI
      strongly predicted lower concentrations of creatine-phosphocreatine (Cre) and
      choline-containing compounds, whereas Cre and N-acetyl-aspartate positively
      correlated with working memory skills. Working memory skills thus seem related to
      frontal lobe energy metabolism, which in turn is related to DI.

PMID- 10955202
TI  - Diminished motor timing control in children referred for diagnosis of learning
      problems.
AB  - Disabled readers exhibit motor timing control (MTC) deficits in bimanual
      coordination relative to average readers. This article evaluates to what extent
      poor MTC is specific to reading or if it is related to learning problems in
      general. Children (7 to 11 years of age) referred for learning impairment (LI; n
      = 100) and same-age children nonlearning impaired (NLI; n = 243) performed a
      paced finger-tapping task. Greater variability of interresponse intervals was
      associated with poorer reading, spelling, and arithmetic achievement. The LI
      group performed more poorly than the NLI group, a difference that persisted even
      after adjusting for reading skill. Poor MTC is associated with poor reading but
      may also be a characteristic of children referred for learning problems, possibly
      signaling increased vulnerability of underlying neural integrative processes
      relevant to the child's adaptation to academic demands, including reading.

PMID- 10955203
TI  - Sex differences on a mental rotation task: variations in electroencephalogram
      hemispheric activation between children and college students.
AB  - The area of cognitive research that has produced the most consistent sex
      differences is spatial ability. In particular, men usually perform better on
      mental rotation tasks than women. Performance on mental rotation tasks has been
      associated with right parietal activation levels, both during task performance
      and prior to performance during baseline recordings. This study examined the
      relations among sex, age, electroencephalogram (EEG) hemispheric activation (at
      the 10.5 Hz to 13.5 Hz frequency band), and 2-D mental rotation task ability.
      Nineteen 8-year-olds (10 boys) and 20 college students (10 men) had EEG recorded
      at baseline and while performing a mental rotation task. Men had a faster
      reaction time on the mental rotation task than women, whereas there were no
      differences between boys and girls. After covarying for baseline EEG power
      values, men exhibited more activation (lower EEG power values) than women in the
      parietal and posterior temporal regions, whereas boys' and girls' power values
      did not differ in the parietal or posterior temporal regions. Furthermore, during
      the baseline condition, men generally exhibited more activation (lower EEG power
      values) throughout all regions of the scalp. Results support the hypothesis that
      a change that affects both brain activation and performance on mental rotation
      tasks occurs sometime between childhood and adulthood.

PMID- 10955204
TI  - Hand preference side and its relation to hand preference switch history among old
      and oldest-old adults.
AB  - The last 10 years of research on adult hand preference patterns have generated a
      controversy over the meaning of the difference in the incidence rates of left-
      and right-hand preference in older adult samples (> 60 years old) when compared
      to samples of younger individuals (< 30 years old). Age differences in hand
      preference prevalence often are studied with large, cross-sectional age samples;
      however, with 1 notable exception (Gilbert & Wysocki, 1992), these large samples
      frequently are dominated numerically by individuals below the age of 45 years.
      This study reports on hand preference data from a sample of 1,277 individuals
      between the ages of 65 and 100 years. Overall, the participants in this sample
      displayed an incidence of 93.1% right preference versus 6.9% left preference.
      However, the occurrence of age differences in right-hand use when the oldest-old
      adults (> 73 years old) were compared to the others in this sample were only
      apparent for writing hand preference. Variation in hand preference prevalence was
      related to whether an individual reported a history of attempts to switch
      preference toward the right side. These findings support the view that age
      related variations in hand preference prevalence are best explained by a number
      of factors, the interaction of which is still not well understood (Hugdahl, Satz,
      Mitrushina, & Miller, 1993; Hugdahl, Zaucha, Satz, Mitrushina, & Miller, 1996).

PMID- 10955205
TI  - A connectionist approach to making the predictability of English orthography
      explicit to at-risk beginning readers: evidence for alternative, effective
      strategies.
AB  - A case is made (and illustrated with empirical data with children) for
      connectionist models that are not only computationally explicit but also
      instructionally explicit. First-graders (N = 128) at the bottom of their classes
      in reading (average 11.5 percentile on nationally normed tests) participated in a
      3-layer intervention. In the first layer, kept constant for all treatment groups,
      the alphabet principle was taught, making functional spelling units and
      alternations explicit. In the second layer, which varied systematically across
      treatment groups, children received different kinds of tutor modeling in learning
      a set of words of varying spelling-sound predictability, using different
      connections between printed and spoken words, singly or in combination. In the
      third layer, also kept constant, children read and discussed illustrated books.
      Over the 4-month, 24-lesson intervention, all 7 treatment groups in the second
      layer improved more in word-specific learning than a contact control group that
      received phonological and orthographic awareness training without explicit
      instruction on orthographic-phonological connections. Of these 7, only 3 kinds of
      explicit modeling (whole word, letter-phoneme, and combined whole word and letter
      phoneme) resulted in greater transfer to untrained words than the contact control
      or the other 4 kinds of explicit modeling. Results are discussed in reference to
      the controversy over whether dual route or connectionist models best account for
      the acquisition of reading.

PMID- 10955206
TI  - Phalangeal and metacarpal fractures of the hand.
AB  - This article addresses the types of metacarpal and phalangeal fractures seen in a
      variety of sports. Treatment options are discussed in depth based on the
      location, configuration, and associated soft-tissue injuries. This article
      provides a greater understanding of the treatment algorithm to minimize the
      possibility of long-term functional consequences for the athlete.

PMID- 10955207
TI  - Proximal interphalangeal joint fracture dislocations.
AB  - Proximal interphalangeal joint fracture dislocations are complex, potentially
      disabling injuries for any patient, especially the competitive athlete. Dorsal
      fracture dislocations are fairly common and volar fracture dislocations are rare.
      Stable injuries often heal with minimal functional deficit, whereas unstable
      injuries can result in limitation in range of motion, joint incongruity, and
      degenerative joint disease. A number of surgical procedures have been described
      to treat the unstable dorsal fracture dislocation, including ORIF, extension
      block pinning, external fixation, dynamic traction, and volar plate arthroplasty.
      Volar fracture dislocations are usually amenable to closed or open reduction and
      internal fixation. The results of treatment of both volar and dorsal fracture
      dislocations can be unpredictable.

PMID- 10955208
TI  - Thumb collateral ligament injuries. An anatomic basis for treatment.
AB  - This anatomic and clinical study leads to the following conclusions: 1. The ulnar
      and radial proper collateral ligaments are the critical lateral stabilizers of
      the thumb MP joint; both are highly vulnerable to complete disruption, with
      resultant disabling joint instability. 2. The intrinsic anatomy of the radial
      side of the MP joint is not a mirror image of the ulnar aspect. Significant
      anatomic differences account for distinctive patterns of instability. Whereas
      disruption of the ulnar collateral ligament in conjunction with dorsal capsular
      tears is apt to result in combined radiovolar subluxation, disruption of the
      radial collateral ligament, coupled with the unopposed dynamic force of the
      adductor pollicis, characteristically is prone to a rapid pathologic sequence of
      profound joint instability, with progressive ulnar and volar subluxation and,
      ultimately, degenerative joint disease. 3. Optimal management of the complete
      collateral ligament lesion requires prompt diagnosis, most accurately confirmed
      with physical and radiographic stress testing, and precise surgical repair.
      Immobilization alone is insufficient treatment for these serious ligament
      disruptions, characterized by considerable displacement with wide separation of
      torn ends. 4. Although early direct repair affords the best opportunity for
      restoration of joint integrity with a highly favorable functional recovery,
      secondary repair and free tendon grafting, prior to joint deformity, provide
      consistently successful options for chronic instability.

PMID- 10955209
TI  - Closed flexor tendon disruption in athletes.
AB  - Closed tendon injuries of the hand and wrist are very common in the athletic
      population. Most of these injuries, especially those involving the extensor
      tendons, can be treated successfully with nonoperative management if seen
      acutely. Acute closed flexor tendon injuries, however, usually require operative
      intervention for the best result. Although evaluation and diagnosis of flexor
      tendon injuries are relatively straightforward, diagnosis is still commonly
      delayed secondary to both delayed presentation and missed diagnoses. If diagnosis
      is delayed, operative intervention becomes less optimal and the patient may have
      a permanent disability regardless of treatment. Generally, athletes are able to
      return to their pre-injury level of participation regardless of treatment. This
      is a product of both the finger involved--usually ring or little--and the extent
      of the disability. In many instances, the athlete may even continue participation
      during treatment with protective splinting.

PMID- 10955210
TI  - Closed injuries to the extension mechanism of the digits.
AB  - Injuries to the extensor mechanism create an imbalance in the precise flexion
      extension system that regulates finger motion. This imbalance results in visible
      and functional deformities. Although these deformities are initially supple, they
      can become fixed and progress to joint degeneration. This article outlines early
      diagnosis and accurate treatment of the most common extensor tendon injuries.
      Avoidance of late sequellae is the goal.

PMID- 10955211
TI  - Boxer's knuckle. Traumatic disruption of the extensor hood.
AB  - The unique function of the boxer's hand requires persistent, forceful punching in
      a constantly clenched fist posture, therefore, the metacarpophalangeal joints are
      continually exposed to blunt trauma and highly vulnerable to injury. This injury
      is traditionally termed boxer's knuckle. Although a myriad of metacarpophalangeal
      joint derangement is apt to result from isolated or repetitive blows inflicted
      and absorbed by the hand, the most serious and disabling type of boxer's knuckle
      is extensor hood disruption. Based on experience with 27 surgical cases, this
      article describes characteristic extensor hood pathology and operative techniques
      that have afforded a consistently favorable outcome.

PMID- 10955213
TI  - Diagnosis and management of hamate hook fractures.
AB  - Hamate hook fractures, although uncommon, are now recognized with increasing
      frequency because of the increase in popularity of racket sports and golf.
      Careful clinical evaluation and adjunctive radiologic investigation help
      establish the diagnosis. Acute nondisplaced fractures can heal with
      immobilization, while displaced fractures and nonunions typically require open
      reduction and internal fixation (acute fractures) or hook excision.

PMID- 10955212
TI  - Management of acute scaphoid fractures.
AB  - Scaphoid fractures in the athlete present a dilemma to the treating clinician.
      Diagnosis of scaphoid fractures should be suspected in any athlete, especially
      those participating in contact sports, presenting with radial wrist pain.
      Appropriate imaging studies should be obtained to make a timely and complete
      diagnosis. Treatment alternatives for acute scaphoid fractures in the athlete
      include casting and staying out of sports, casting with use of a playing cast,
      and internal fixation. Displaced unstable fractures and proximal pole fractures
      should be treated by open reduction and internal fixation. Nondisplaced mid-third
      fractures are the most common type seen in the athlete. Alternatives of treatment
      should be carefully explained to the patients and family and the most appropriate
      treatment employed.

PMID- 10955214
TI  - Acute fractures of the distal radius.
AB  - Distal radius fractures commonly are sustained by athletes during competition.
      Typically, these are high energy injuries with severe displacement, metaphyseal
      comminution, and articular surface disruption. Each fracture is distinguished by
      its degree of articular displacement, stability, and reducibility. Management is
      contingent on recognition of the variable magnitude of articular disruption and
      skillful treatment based on specific fracture configuration.

PMID- 10955215
TI  - Rotary subluxation of the scaphoid. Revisited.
AB  - The SL ligament complex and volar radiocarpal ligaments provide scaphoid
      stability both at the SL joint and, more importantly, at its distal radius
      articulation. With disruption or attenuation of these ligaments, rotational
      displacement of the scaphoid occurs about its longitudinal axis. This results in
      distal scaphoid flexion and proximal pole subluxation dorsally, toward the distal
      radius rim. Rotary subluxation of the scaphoid accurately describes this
      condition, and represents a spectrum of radioscaphoid instability based upon the
      severity and chronicity of ligamentous disruption. Diagnosis is based upon
      identification of specific clinical and radiographic features. Recognition of
      this entity provides for a more rational basis for treatment of ligamentous
      injuries of the wrist.

PMID- 10955216
TI  - Lunotriquetral injuries in the athlete.
AB  - The athlete with an LT injury typically presents with ulnar-sided wrist pain
      after a high-energy impaction of the wrist. Reagan's LT ballottement test and
      Kleinman's shear test help the examiner identify these injuries. A thorough
      radiographic examination includes standard PA and lateral radiographs. Magnetic
      resonance imaging or arthrography can be performed, but the sensitivity of these
      imaging studies varies. The palmar portion of the LT interosseous ligament,
      dorsal radiocarpal ligament, and dorsal intercarpal ligament play the most
      significant roles in LT stability. Lunotriquetral injuries without instability
      respond well to immobilization. Arthroscopy is valuable in staging and
      determining treatment but requires a thorough radiocarpal and midcarpal
      examination. Acute LT injuries with instability are treated with arthroscopic
      assisted reduction and pinning. If desired, this procedure can be incorporated
      with an open ligament repair through a volar approach. Chronic LT tears without
      instability can also be treated arthroscopically. Treatment of the chronic LT
      tear with instability depends on the degree of collapse. Treatment in the athlete
      includes ligament reconstruction with capsulodesis or, rarely, intercarpal LT
      arthrodesis.

PMID- 10955217
TI  - Perilunate injuries. Repair by dual dorsal and volar approaches.
AB  - Controversy persists regarding optimal management of perilunate injuries.
      Traditionally, closed treatment, with or without percutaneous pin fixation, was
      advocated for these highly unstable carpal disruptions, but the inconsistent and
      often disappointing outcome of closed reduction, coupled with the recognition
      that functional recovery closely parallels the accuracy of restoring carpal
      alignment, have led to increasing enthusiasm for open treatment. The favorable
      outcome reported in this article supports both the contention that the acute
      perilunate injury affords the opportune time for operative preservation of carpal
      stability and the efficacy of the combined dorsal and volar approaches as the
      optimal means of surgical repair. This clinical experience also corroborates
      experimental evidence that perilunate injuries are apt to cause a predictable
      spectrum of osseous and soft tissue lesions--lesions usually suitable for early,
      precise repair. For the skilled athlete, prompt recognition and precision
      treatment of all components of injury are the critical factors to attain a
      functional outcome commensurate with a successful return to competition.

PMID- 10955219
TI  - The role of arthroscopy in the evaluation and treatment of triangular
      fibrocartilage complex injuries in athletes.
AB  - Treating athletes with TFCC injuries can be a difficult but very rewarding
      undertaking. Each athlete has individual priorities and concerns, ranging from
      general health and fitness for the recreational athlete to earning or potentially
      earning a living as a professional athlete. It is crucial for the treating
      surgeon to understand these issues to offer the appropriate treatment options at
      the appropriate time. Triangular fibrocartilage complex injuries are quite common
      in athletes because of the high loads placed on the ulnar side of the wrist,
      especially with ulnar-neutral and positive variance. The goal of treatment for
      the competitive athlete with a TFCC lesion is to hasten maximal recovery and
      return the athlete to participation at the pre-injury level of performance. Early
      wrist arthroscopy and treatment of TFCC pathology in this population is certainly
      a real and valuable treatment option. As has been stated, "the TFCC is the new
      frontier of wrist surgery" and arthroscopy has helped blaze the trail to this
      frontier. Competitive and recreational athletes alike benefit from arthroscopic
      treatment of their TFCC injuries.

PMID- 10955218
TI  - Acute injuries of the distal radioulnar joint.
AB  - Distal radioulnar joint injuries can occur in isolation or in association with
      distal radius fractures, Galeazzi fractures, Essex-Lopresti injuries, and both
      bone forearm fractures. The authors have classified DRUJ/TFCC injuries into
      stable, partially unstable (subluxation), and unstable (dislocation) patterns
      based on the injured structures and clinical findings. Clinical findings and
      plain radiographs are usually sufficient to diagnose the lesion, but axial CT
      scans are pathognomonic. Diagnostic arthroscopy is the next test of choice to
      visualize stable and partially unstable lesions. Stable injuries of the DRUJ/TFCC
      unresponsive to conservative measures require arthroscopic debridement of the
      TFCC tear, along with ulnar shortening if there is ulnar-positive variance.
      Partially unstable injuries, on the other hand, are treated with direct
      arthroscopic or open repair of the TFCC tear, once again, along with ulnar
      shortening if ulnar-positive variance is present. Unstable injuries include
      simple and complex DRUJ dislocations. A simple DRUJ dislocation is easily
      reducible but may be stable or unstable. In complex dislocation, reduction is not
      possible because there is soft tissue interposition or a significant tear. After
      the associated injury is dealt with, treatment for complex injuries requires
      exploration of the DRUJ, extraction of the interposed tissue, repair of the soft
      tissues, and open reduction and internal fixation of the ulnar styloid fracture
      (if present and displaced). The early recognition and appropriate treatment of an
      acute DRUJ injury are critical to avoid progression to a chronic DRUJ disorder,
      the treatment of which is much more difficult and much less satisfying.

PMID- 10955221
TI  - Ulnar neuropathy with and without elbow instability.
AB  - Increased valgus stresses on the medial aspect of the elbow can result in a
      number of bony and soft-tissue abnormalities. The most common abnormalities are
      ulnar neuropathy and valgus instability secondary to injury of the medial
      collateral ligament. Diagnosis and treatment of these disorders are discussed in
      this article.

PMID- 10955220
TI  - Vascular pathology in the throwing athlete.
AB  - Vascular pathology in the upper extremity of a throwing athlete comprises a
      spectrum of serious disorders apt to threaten the patient's career and the
      viability of the involved parts. Such pathology includes digital vessel
      thrombosis, proximal thrombosis with distal embolization, vessel aneurysm, and
      vessel compression, such as in thoracic outlet syndrome and quadrilateral space
      syndrome. This article provides a description of vascular disorders prone to
      result from sports activities and a review of published data relevant to throwing
      athletes. Recognition of vascular compromise as a cause for dead arm syndrome or
      painful digital dysfunction among athletes is essential to prevent the grave
      consequences of progressive ischemia.

PMID- 10955222
TI  - Management of acute and chronic biceps tendon rupture.
AB  - In conclusion, the authors believe that younger high-demand patients should be
      offered the option of surgical repair; can be performed through the preferred
      single anterior incision with two suture anchors. Chronic tears, even with
      retraction, may be successfully reconstructed using a free tendon graft, often
      the flexor carpi radialis. Complications, including radial nerve palsy and
      proximal radioulnar synostosis, can be avoided with the single-incision
      technique. Older, low-demand patients can be rehabilitated and have excellent
      function without acute repair. Partial tendon injuries, for the most part, may be
      treated with rest and rehabilitation and explored only for chronic, unremitting
      pain. The authors believe that the single anterior approach should be used over
      the previously popularized two-incision technique.

PMID- 10955223
TI  - Epicondylitis--lateral and medial. A problem-oriented approach.
AB  - Epicondylitis will remain a problematic condition until we better understand the
      nature of the degenerative condition. Nonoperative management still is the most
      common treatment, but those patients who are disabled when this fails can expect
      improvement after surgery.

PMID- 10955224
TI  - [New diagnosis of cerebrospinal fluid fistulas].

PMID- 10955225
TI  - [Detection of nitric oxide synthases in physiological and pathophysiological
      processes of the nasal mucosa].
AB  - Nitric oxide (NO) can play an important role in the regulation of vascular tone
      and neurotransmission, as well as in non-specific immunoreactions and
      inflammation in a variety of tissues. Increased quantities of nitric oxide in
      respired air can be measured during inflammatory processes. However, the exact
      role and precise sources of NO under physiological and pathophysiological
      conditions within the airways remain to be defined. Three isoforms of NO
      synthases can be distinguished: two constitutive (neuronal and endothelial)
      Ca(2+)-dependent cNOS and one inducible Ca(2+)-independent iNOS (NOS II).
      Constitutive NOS (NOS I and III) release a basal amount of NO under physiological
      conditions. The inducible form once expressed can catalyse the generation of
      large quantities of NO. Many kinds of cells, such as macrophages, neutrophils,
      endothelium and smooth muscle cells, are capable of expressing NOS II. Since all
      isoforms of NO-synthase seem to be present in nasal tissues and the expression of
      iNOS under inflammatory conditions seems to be responsible for excessive
      production of NO, the distribution of NOS-isoforms (especially NOS II) in normal
      and inflammatory nasal tissue, as well as the exact requirements for expression
      of iNOS remain to be proven. Non-inflamed fresh human nasal mucosa from the
      middle turbinate was compared immuno-histologically with nasal mucosa having the
      typical findings of chronic polypoid rhinosinusitis (i.e., polypoid middle
      turbinates and polyps of the middle nasal duct). In order to gain more
      information about the mechanisms of acute inflammation, non-inflamed vital
      turbinates were incubated in vitro with the proinflammatory substances bacterial
      lipopolysaccharides (LPS) and tumor necrosis-factor (TNF) for 30, 60, 90, 120,
      180 and 240 min. Subsequent to exposure to NADPH-diaphorase and immunostaining
      with specific antibodies to each NOS-isoform, clearly increased or initiated
      expressions of inducible NOS (iNOS) in blood vessels, glands, macrophages and
      epithelium of chronically inflamed and LPS-incubated nasal tissue became apparent
      in comparison to the non-inflamed controls. In contrast, NOS III/NOS I seemed to
      be not affected. The onset of immunohistochemically recognizable NOS II
      expression was observed after 90 min incubation with of LPS/TNF-alpha. Polypoid
      tissue showed a strong increase in submucosal thickness and a high infiltration
      of iNOS-positive leukocytes (granulocytes and macrophages) compared to the LPS
      incubated non-inflamed specimens. These findings implicate NOS II generated
      nitric oxide as a key agent for causing swelling, secretion and obstruction in
      patients with acute and chronic polypoid or allergic rhinitis. These findings
      also suggest that molecular NO has to be considered in the pathophysiology of
      chronic polypoid rhinosinusitis.

PMID- 10955226
TI  - [Beta-trace protein in diagnosis of cerebrospinal fluid fistula].
AB  - Beta-trace protein is a lipocalin that was recently identified as prostaglandin D
      synthase and represents a major constituent of human cerebrospinal fluid. Beta
      trace protein, similar to beta 2-transferrin, has been used as an immunological
      marker for the detection of cerebrospinal fluid. Between 1982 and 1999, 130
      specimens from 101 patients with suspected cerebrospinal fluid leaks of the
      anterior or lateral skull base have been investigated for beta-trace protein. The
      specimens were analyzed by one-dimensional immunoelectrophoresis using Laurrell's
      electroimmunoassay. In all, beta-trace protein could be detected in 57 specimens
      and was absent in 73. All case notes were studied retrospectively. In correlation
      with the clinical course and the findings of CT of the paranasal sinuses, high
      resolution CT of the petrous bones, CT cisternography, NMR, 111In-DTPA
      radionuclide cisternography, intraoperative findings, visualization of sodium
      fluorescein stained cerebrospinal fluid using endoscopic blue light or testing
      for glucose, there was no false-positive result. A false-negative result occurred
      in two cases. These findings show that the beta-trace test has a sensitivity of
      97.3% and a specificity of nearly 100%. Our findings show that analysis of beta
      trace protein can be a valuable test for detecting CSF leakage and has certain
      advantages in comparison with the beta 2-transferrin assay.

PMID- 10955227
TI  - [Anatomy of the glottis and subglottis in the pediatric larynx].
AB  - BACKGROUND: The morphological development of the human larynx during the first
      years of life has previously not been studied in detail and has mainly been
      described on a qualitative basis. This study seeks to provide detailed
      morphometric data on the regular anatomy of the vocal cords, the subglottic
      airway and the tracheal airway dimensions gained from plastinated whole organ
      serial sections of 43 infant larynges and to determine morphological changes with
      age. Such information may be useful for the understanding of pediatric airway
      disease or for laryngeal surgery in children. MATERIAL AND METHODS: The larynges
      of 43 children aged 1 to 60 months were plastinated. Whole organ serial sections
      were obtained by cutting the resulting specimen with a diamond band saw.
      Morphometry of whole-organ sections was accomplished using a high resolution,
      computer-based image analyzer. The total length of the glottis, length of the
      cartilaginous and ligamentous glottis, subglottic cartilaginous cross-section,
      subglottic airway and tracheal airway were determined for each specimen. RESULTS:
      The subglottic airway increases considerably in size during the first 2 years of
      life (from 13 to 28 mm2 in the means). Further growth seems to follow a linear
      mode. The relative proportion of the mucosal lining of the subglottic airway
      decreases likewise. While it occupies approximately 50% of the subglottic
      cartilaginous cross-section during the first two years of age, its relative
      proportion decreases to some 30 to 40% between age three to five. Other than in
      adults, and comparable to most mammals, the cartilaginous glottis accounts for 60
      to 75% of the vocal folds' length in children under two years of age. The
      anterior ligamentous part of the glottis outsizes its posterior cartilaginous
      portion during the third year of life. CONCLUSION: This study supplies detailed
      morphometric data on the growth and structure of the human larynx during the
      first years of life that have not been available to date. Previous studies on the
      anatomical configuration of the infant larynx have focused on the the perinatal
      larynx, the prepuberal and puberal larynx, and the development of collagen fibres
      in the developing larynx. The human larynx has undergone significant evolutionary
      adaptations. Among them are the descent of the larynx, the capability of vocal
      fold adjustment in length, tension and shape, and the prominent configuration of
      the membranous part of the vocal folds as opposed to the cartilaginous part. The
      infant larynx is not just a miniature of the adult organ. It shows differences in
      its position relative to the vertebrate column, in the composition of cartilages
      and soft tissues, and in environmental adaptation. The present study is the first
      to supply detailed morphometric data on the growth and structure of the human
      larynx during the first five years of life and on the morphological changes of
      the larynx during this period. From these data it seems that some of the adaption
      of the human larynx as opposed to other vertebrates are not fully developed at
      birth, but undergo postnatal maturation. The relative proportions of the
      cartilaginous and membranous parts of the vocal folds clearly demonstrate this
      maturation process: While the posterior "respiratory" glottis accounts for some
      sixty to 75% of the total glottic length in newborns, its relative proportion
      decreases throughout the first years of life and finally equals the proportions
      of the adult larynx. Other than in adults, and in accordance with the literature,
      no sexual dimorphism of the larynx could be detected in this series of infant
      larynges. Morphometric data on the growth and structure of the human vocal folds
      and the subglottic airway during childhood are presented. Plastinated whole organ
      serial sections were used in the study to show the infant laryngeal morphology.
      The study provides quantitative anatomical data of clinical interest that light
      up the anatomy of the pediatric airways.

PMID- 10955228
TI  - [Management of complications after prosthetic voice rehabilitation].
AB  - The growing popularity of prosthetic voice restoration after total laryngectomy
      confronts ENT specialists with an increasing number of prosthesis-related
      complications. The ENT specialist should be familiar with the management of these
      complications in order to maintain the patients speech and social rehabilitation.
      In a retrospective study on 108 consecutive patients, complications were
      encountered in 30%. The incidence was not related to the factors age or primary
      vs. secondary insertion of the prosthesis. Complications consisted of formation
      of granulation tissue (15.7%), shunt dilatation (5.5%), loss of prosthesis
      (3.7%), local cellulitis (2.8%), extrusion (1.9%), ingrowth of prosthesis (1.9%)
      and formation of excessive scar tissue with dislocation of prosthesis (0.9%).
      Permanent removal of the prosthesis due to complications was necessary in 3 cases
      (2.8%). Therapeutic measures for the management of complications are described
      and evaluated. The treatment of complications was well tolerated by all patients
      and led to satisfying results in most cases. Our observations show that
      prosthetic voice rehabilitation is associated with various difficulties and
      complications, but that these can be handled quite easily and successfully in the
      majority of cases.

PMID- 10955229
TI  - [Functional and esthetically oriented reconstruction of lip defects].
AB  - Reconstruction of lip defects presents a challenge to the surgeon. Apart from
      attaining a good aesthetic result, preserving the function of the oral sphincter
      is an essential objective. A variety of techniques and modifications of
      procedures for reconstructing lip defects have been reported in the literature.
      It is up to the surgeon to select the reconstruction procedure ensuring optimum
      functional and cosmetic results, depending on the location, size, and depth of
      the defect. The division of the lips into aesthetic subunits can prove very
      beneficial in designing lip reconstruction procedures. The upper lip is divided
      into three aesthetic subunits: two lateral subunits and a median subunit, the
      philtrum. The lower lip constitutes a single subunit. In this study, established
      reconstruction techniques are discussed and a concept serving to facilitate the
      appropriate choice of technique is introduced. This concept differentiates
      between vermilion defects on the one hand, and partial-thickness and full
      thickness lip defects on the other hand. For the lower lip, the full-thickness
      defects are classified as defects involving one-third, one-third to two-thirds of
      the lower lip width, and between two-thirds and complete loss of lip tissue. For
      the upper lip, a distinction is made between isolated defects of the central and
      lateral subunits and combined defects of the central and lateral subunits.
      Important principles of surgery and the advantages or disadvantages of different
      reconstruction techniques are discussed.

PMID- 10955230
TI  - [Diagnosis and therapy of laryngitis gastrica].
AB  - We treated 64 patients with the diagnosis of laryngitis gastrica with Antra
      (Omeprazol) in doses of 10, 20, and 40 mg. To determine the success of the
      therapy, pH monitoring of the esophagus and hypopharynx, the voice status and
      measurement of vocal penetrating capacity were used. The results prove that a 20
      mg dose of Antra is suitable for the therapy of laryngitis gastrica with a high
      rate of success. Problems which arose during the investigation, consequent
      changes of the original concept of the project as well as new aspects and
      questions which resulted from this are discussed with respect to further
      investigation.

PMID- 10955231
TI  - [Neurinoma of the nasal cavity].
AB  - A 35 years old male patient presented with serous nasal secretion, relapsing
      epistaxis and a slowly progredient nasal obstruction. Clinical examination and CT
      scans showed a tumor occupying the left middle meatus and the whole nasal cavity
      displosing the nasal septum to the right side. The tumor was resected by a
      midfacial degloving approach. Histological examination showed a neurinoma. By
      means of the presented case report and a review of literature, diagnosis and
      treatment of this rare nasal tumor are discussed.

PMID- 10955232
TI  - [Maximal help by minimal intervention? The treatment of chronic patients].

PMID- 10955233
TI  - [News regarding medical legislation for the period April 1999 to October 1999].

PMID- 10955234
TI  - [Chronic swelling in the sublingual region and submental region. Dermoid of the
      mouth floor].

PMID- 10955235
TI  - [Current aspects of nasal glucocorticosteroid therapy].

PMID- 10955237
TI  - [Results of antimicrobial susceptibilities of strains clinically isolated at 8
      institutions in Hiroshima City to major oral antimicrobial drugs, mainly new
      quinolone drugs. Hiroshima Levofloxacin Susceptibility Surveillance Group].
AB  - To evaluate the resistance for major oral antimicrobial agents, mainly new
      quinolones, we carried out a drug susceptibility surveillance of 3,050 strains of
      11 microbial species clinically isolated at 8 institutions such as general
      hospitals and examination centers in Hiroshima city. 10 antimicrobial agents were
      used: 3 new quinolone drugs, 5 beta-lactam drugs, minocycline and clarithromycin.
      Among Gram-positive bacteria, methicillin resistant Staphylococcus aureus (MRSA)
      and Enterococcus faecalis showed low susceptibility to the new quinolone drugs,
      while methicillin susceptible Staphylococcus aureus (MSSA) and Streptococcus
      pneumoniae were highly sensitive to these drugs. Among Gram-negative bacteria,
      Pseudomonas aeruginosa showed high resistance for the new quinolone drugs, but
      enteric bacteria and Haemophilus influenzae did not show marked resistance,
      maintaining almost good sensitivity to these drugs. To reduce the appearance of
      resistant bacteria, appropriate antimicrobial agents should be selected. Drug
      susceptibility surveillance in the community will be also important in the
      future.

PMID- 10955236
TI  - [Activities of antimicrobial agents against 5,180 clinical isolates obtained from
      26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group].
AB  - The surveillance study was conducted to determine the antimicrobial activity of
      fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other
      20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical
      institutions during 1998 in Japan. The resistance to fluoroquinolones was
      remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas
      aeruginosa from UTI. However, many of the common pathogens such as Streptococcus
      pneumoniae including penicillin-resistant isolates, methicillin-susceptible
      Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae,
      Haemophilus influenzae including ampicillin-resistant isolates have been kept to
      be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI
      were susceptible to fluoroquinolones. In conclusion, the results from this
      surveillance study suggest that fluoroquinolones are useful in the treatment of
      various bacterial infections including respiratory infections.

PMID- 10955238
TI  - [Colony PCR for rapid detection of antibiotic resistance genes in MRSA and
      enterococci].
AB  - We examined colony PCR that does not use the prepared template DNA but intact
      cells as the template DNA source for the rapid, simple and reproducible detection
      of antibiotic resistance genes in strains of methicillin-resistant Staphylococcus
      aureus (MRSA) and Enterococcus. Two factors turned out to be important; i.e. the
      transfer size of bacterial cells and the use of DNA Polymerase with high
      performance. In practice, the tip of a toothpick was lightly touched with a
      colony on agar plates followed by the PCR mixture (20 microliters) containing KOD
      plus-DNA Polymerase and multiplex primers. The cell transfer size ranged from
      10(3) to 10(4) cfu and 30 cycles of PCR (95 degrees C, 30 sec.-->50 degrees C, 30
      sec.-->72 degrees C, 60 sec.) following the first heating (95 degrees C, 3 min.)
      resulted in good amplification of the target regions of mecA and aac(6')/aph(2")
      that are responsible for the resistance to methicillin and arbekacin,
      respectively.

PMID- 10955240
TI  - Criteria for evaluation of clinical efficacy of antimicrobial agents on urinary
      tract infection. UTI Subcommittee of the Clinical Evaluation Committee, Japan
      Society of Chemotherapy.

PMID- 10955239
TI  - [A comparative study on the clinical utility of cefozopran and cefpirome against
      complicated urinary tract infections].
AB  - Aiming at evaluating the utility of cefozopran (CZOP) against complicated urinary
      tract infections with the velocity of eradication of causal bacteria in early
      treatment and clinical efficacy by new criteria of UTIs, a comparative study was
      conducted using cefpirome (CPR) as the control drug. CZOP and CPR were
      administered by intravenous drip infusion at a dose of 1 g twice daily. The
      duration of treatment was for 5 days. The study method involved randomized
      assignment of the subjects to either group CZOP or group CPR. The results were as
      follows: 1. Of a total of 80 cases treated, 65 (CZOP group--32 cases, CPR group-
      33 cases) were evaluated for efficacy. 2. The overall clinical efficacy
      evaluation according to the criteria proposed by Japanese UTI Committee rated the
      CZOP group as 90.6% (29/32), and the CPR group as 90.9% (30/33), with no
      significant difference between the 2 groups. Clinical efficacy evaluated by
      attending physicians rated the CZOP group as 93.8% (30/32) and the CPR group as
      90.9% (30/33). There was no significant difference between the 2 groups. 3. The
      efficacy rates to pyuria on day 2 were 26.7% and 0% for the CZOP group and the
      CPR group, respectively, indicating a higher efficacy rate for the former (p <
      0.05). Those on after treatment were 59.4% and 54.5% for the CZOP group and the
      CPR group, respectively, with no significant difference between the 2 groups. 4.
      Regarding the bacteriological effect, the eradication rates of both groups were
      over 90% on day 1 and after treatment. There was no significant difference
      between the 2 groups. 5. Side effects occurred in 1 case (2.6%) out of 39 in the
      CZOP group and in 1 case (2.4%) out of 41 in the CPR group. Laboratory test value
      fluctuation was noted in 8 (20.5%) of 39 cases in the CZOP group and 11 (26.8%)
      of 41 cases in the CPR group. There was no significant difference between the 2
      groups. The results indicate that CZOP achieves an early efficacy to pyuria, and
      is as useful as CPR against complicated urinary tract infections.

PMID- 10955241
TI  - Effect of clinical and semen characteristics on efficacy of ovulatory stimulation
      in patients undergoing intrauterine insemination.
AB  - PURPOSE: We measured the effect of ovulatory stimulation (OS) upon intrauterine
      insemination (IUI) success rates, particularly among patients with risk factors
      for IUI failure. METHODS: Retrospective review of medical and laboratory results
      from 512 patients who underwent 1576 cycles of IUI with partner's sperm over a 3
      year period. Data were collected on 3 risk factors for IUI failure (advanced
      female age > 37.7 years, prior corrective pelvic surgery, and poor post-wash
      sperm motility), and on method of OS (none, clomiphene citrate, or gonadotropin).
      RESULTS: Patients who underwent OS had significantly higher pregnancy rates
      (7.6%) than those who did not (4.7%, p = 0.02). However, when patients were
      stratified by their risk factors, OS made a significant difference only for
      patients without risk factors. These patients had a 15.5% per cycle pregnancy
      rate with OS, compared to 7.9% in unstimulated IUI cycles (p = 0.04).
      CONCLUSIONS: Ovulatory stimulation doubles IUI pregnancy rates among young
      patients without a prior pelvic surgery and with good post-wash semen quality.
      The benefit of OS for patients with risk factors for IUI failure is unclear.
      These patients should be counseled that their chances for success with IUI are
      limited, with or without OS.

PMID- 10955242
TI  - Pentoxifylline initiates motility in spontaneously immotile epididymal and
      testicular spermatozoa and allows normal fertilization, pregnancy, and birth
      after intracytoplasmic sperm injection.
AB  - PURPOSE: Pentoxifylline (PF) has been used to enhance sperm motility in many in
      vitro fertilization programs. The twofold purpose of this study was to determine
      whether PF stimulates fresh or frozen epididymal and testicular totally immotile
      spermatozoa and whether it can be used to select viable spermatozoa for
      intracytoplasmic sperm injection (ICSI). METHODS: To test the effect of PF on
      motility, 10 samples of totally immotile spermatozoa were incubated for 10 min
      with 3.6 mM PF. Motility was initiated in all cases (14.8% mean motility after PF
      treatment of five samples of fresh or frozen epididymal spermatozoa and 13.6%
      mean motility of five samples of fresh or frozen testicular spermatozoa). To
      assess PF for selection of viable spermatozoa before ICSI, we compared the
      outcome of ICSI in 20 cycles using fresh or frozen epididymal or testicular PF
      treated immotile spermatozoa and 139 control ICSI using fresh or frozen
      epididymal or testicular spontaneously motile spermatozoa. RESULTS: Fertilization
      rates were similar in the PF and control groups (45.2% vs. 51.0%). Embryo quality
      and division stages at the time of transfer were comparable. Six pregnancies
      occurred in PF-ICSI group (30.0% per cycle vs. 26.6% in control group) including
      two deliveries of healthy children and four ongoing pregnancies.

PMID- 10955244
TI  - Intracytoplasmic sperm injection increases embryo fragmentation without affecting
      clinical outcome.
AB  - PURPOSE: To examine the effect of intracytoplasmic sperm injection (ICSI) on
      embryo fragmentation and implantation rates in those embryos chosen for transfer
      compared to conventional in vitro fertilization (IVF). METHODS: We compared 253
      infertility patients (71 ICSI and 182 IVF) with respect to age, semen analysis,
      number of embryos transferred, embryo fragmentation, implantation rate, and
      pregnancy rate. Embryo fragmentation was determined by one observer at the same
      laboratory over the entire study period. RESULTS: A statistically significant
      difference was observed in mean embryo grade between IVF (2.2 +/- 0.84) and ICSI
      (2.5 +/- 0.77), P = 0.01. Additionally, the IVF patients had significantly more
      nonfragmented (grade I) embryos compared to the ICSI group, P < 0.01.
      CONCLUSIONS: These data suggest that ICSI, irrespective of semen parameters, may
      increase embryo fragmentation and produce fewer nonfragmented grade I embryos
      while maintaining implantation and pregnancy rates similar to conventional IVF.

PMID- 10955243
TI  - Salpingectomy for repeated embryo nonimplantation after in vitro fertilization in
      patients with severe tubal factor infertility.
AB  - PURPOSE: To evaluate the impact of salpingectomy on the rates of embryo
      implantation and pregnancy in patients with severe, irreversible tubal factor
      sterility. METHODS: A retrospective study of patients with repeated failure of in
      vitro fertilization due to nonimplantation of the embryo. Seventy-two patients
      with severe and irreversible tubal factor sterility were selected following
      repeated failure of in vitro fertilization (IVF) due to assumed nonimplantation
      of the embryo: 35 underwent a salpingectomy before continuing IVF cycles and 37
      continued IVF cycles without salpingectomy. RESULTS: After the first IVF cycle
      consecutive to diagnosis of embryo nonimplantation, the implantation rate was
      10.2% in the salpingectomy group and 6.1% in the group without the procedure (P =
      0.5). After all IVF cycles, the rate was, respectively, 6.9% and 4.5% (P = 0.2).
      Salpingectomy improved the pregnancy rate (PR) per transfer (23.5% vs. 9.9%; P =
      0.01). The curves of the cumulative probability of becoming pregnant show that
      salpingectomy resulted in pregnancy more rapidly. CONCLUSIONS: Salpingectomy
      improves the PR per transfer in patients with severe and irreversible tubal
      factor sterility who have experienced repeated failure of IVF due to embryo
      nonimplantation. This procedure also reduces the number of IVF attempts needed to
      obtain pregnancy.

PMID- 10955245
TI  - Two different timings of intrauterine insemination for non-male infertility.
AB  - PURPOSE: Our purpose was to assess the simplicity and convenience of treatment
      scheduled not on weekends, by comparing two different timings of intrauterine
      insemination (IUI) protocol. METHODS: A prospective observational study of two
      different protocols of intrauterine insemination was designed. Two hundred and
      ten infertile couples with normal spermiograms were included in this study. Fifty
      eight couples were treated with IUI 26 to 28 h after human chorionic gonadotropin
      (hCG) injection plus timed intercourse within a 12- to 18-hr period and 147
      couples had IUI 36 to 38 hr after hCG injection and timed intercourse within a 12
      to 18-hour period. Pregnancy rates were compared with two different protocols of
      IUI. RESULTS: The mean age, duration, and causes of infertility and the cycle
      characteristics following follicular stimulation were similar between the two
      groups. The cycle characteristics of follicular stimulation in the two treatment
      groups were not different. There also were no significant differences between the
      groups in the type of sperm concentration, sperm motility, and the percentage of
      sperm with normal morphology per insemination. The number of follicles greater
      than 17 mm per patient was not significantly different between the two groups.
      The pregnancy rate per cycle also was similar between the two groups in men with
      lower motile sperm numbers (< 40 x 10(6)) (23.6% vs. 23.4%) and in men with
      higher sperm numbers (> or = 40 x 10(6)) (25% vs. 24.4%). CONCLUSIONS: The
      different timing but similar efficacy of these two IUI protocols provides a
      practical choice to clinicians. The availability of both protocols may avoid
      unnecessary scheduling of clinical and laboratory work on weekends and holidays
      in women participating in controlled ovarian hyperstimulation and IUI programs
      for treatment of non-male infertility.

PMID- 10955246
TI  - The effects of cryopreservation on semen from men with sarcoma or carcinoma.
AB  - PURPOSE: This study evaluated prefreeze and postthaw semen quality before
      treatment in patients with different types of sarcomas and carcinomas to
      determine whether cryopreservation would be of value for these patients. METHODS:
      Semen specimens were obtained from 50 normal donors and from 21 patients with
      carcinoma and from 14 patients with sarcoma. The specimens were cryopreserved by
      a standard freezing procedure using TEST-Yolk buffer. Prefreeze and postthaw
      sperm motion characteristics were measured. RESULTS: Prefreeze total motile sperm
      count was significantly higher in donors (median: 129.6 x 10(6)/ml) than in men
      with carcinoma (46.9 x 10(6)/ml, P < .001) or sarcoma (66.3 10(6)/ml, P = .04).
      The percent motility and percent linearity were significantly lower in patients
      with carcinoma. In postthaw specimens, total motile sperm count, curvilinear
      velocity, and linearity were significantly lower in patients with carcinoma.
      CONCLUSIONS: The two patient groups in this study had poor semen quality when
      compared with healthy donors both before and after cryopreservation. Sarcoma
      patients had better semen quality than carcinoma patients. As cancer therapy in
      these men could significantly impair their reproductive potential, these men
      should be advised to preserve their semen before starting treatment.

PMID- 10955247
TI  - Relationships between concentrations of tumor necrosis factor-alpha and nitric
      oxide in follicular fluid and oocyte quality.
AB  - PURPOSE: Our objective was to explain a relationship between concentrations of
      tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in follicular
      fluid, oocyte quality, and outcomes of in vitro fertilization--embryo transfer
      (IVF-ET). METHODS: The concentrations of TNF-alpha and NO were measured in 115
      follicular fluid samples collected from 43 patients undergoing IVF-ET program,
      due to tubal obstruction, some with endometriosis (8 patients) or hydrosalpinx (5
      patients). A correlation of these factors concentrations and the oocyte quality,
      the oocyte maturity, and infertility-associated diseases was analyzed. RESULTS:
      No correlation was found between concentrations of NO and TNF-alpha in follicular
      fluid. NO concentrations in follicular fluids were significantly higher in
      patients with endometriosis (P < 0.001) or hydrosalpinx (P < 0.01) compared to
      the patients with just tubal obstruction. Follicular NO concentration differences
      according to oocyte maturity and oocyte quality were not found. In contrast, TNF
      alpha concentrations in follicular fluids were significantly higher in poor
      quality oocytes (P < 0.05) but were not associated with infertility-associated
      diseases, such as hydrosalphinx or endometriosis,and the oocyte maturity. No
      significant differences in follicular levels of NO and TNF-alpha as well as IVF
      ET parameters of pregnant and nonpregnant groups were revealed. CONCLUSIONS:
      There is no significant correlation between the concentrations of NO and TNF
      alpha in follicular fluid. NO levels in follicular fluid are altered in
      infertility-associated diseases. However, TNF-alpha levels but not NO levels
      influence oocyte quality. These results suggest that the production of NO and TNF
      alpha in follicular fluid may be regulated via different pathways and can be
      tempered with infertility-associated diseases, thereby influencing oocyte quality
      locally.

PMID- 10955248
TI  - Pregnancy after preimplantation genetic diagnosis by fluorescence in situ
      hybridization using 18-, X-, and Y-chromosome probes in an infertile male with
      mosaic trisomy 18.

PMID- 10955249
TI  - Repeated oocyte maturation block.

PMID- 10955250
TI  - Successful pregnancies in a case of retrograde ejaculation associated with
      tethered spinal cord syndrome.

PMID- 10955251
TI  - [Risk factors and physical activity levels at the onset of acute myocardial
      infarction in young men].
AB  - OBJECTIVES: The pathogenesis and triggering factors of acute myocardial
      infarction in young men remain unknown. To clarify the pathogenesis of acute
      myocardial infarction in young Japanese men, we compared the clinical features of
      patients with acute myocardial infarction in 2 age groups in Japan. METHODS:
      There were 37 male patients aged < 40 years (Young group; mean age 36 +/- 4
      years, range 23-39 years) among 2,879 patients with acute myocardial infarction
      admitted to the coronary care unit of the National Cardiovascular Center, Japan,
      from 1977 through 1996. The clinical features of this group were compared with
      those of 110 consecutive male patients with acute myocardial infarction aged > or
      = 65 years (Old group; mean age 72 +/- 6 years, range 65-96 years) admitted in
      1993-1994. Demographic features, physical activity levels at or within 2 hours
      before the onset of acute myocardial infarction, and coronary angiographic
      findings were analyzed. RESULTS: Compared with the Old group, the Young group had
      lower incidences of hypertension (p < 0.01) and diabetes mellitus (p < 0.01), a
      higher incidence of smoking (p < 0.01), higher levels of total cholesterol (p <
      0.05) and body mass index (p < 0.05), and a lower level of high-density
      lipopotein (HDL)-cholesterol (p < 0.01). Also, the Young group had a higher
      prevalence of 0-1 vessel disease than the Old group (72% vs 35%, p < 0.01). The
      physical activity level was significantly higher in the Young group than in the
      Old group (2.6 +/- 2.2 vs 1.8 +/- 1.1 METs, p < 0.01). Furthermore, patients with
      multivessel disease in the Young group had a higher incidence of hypertension, a
      higher level of total cholesterol and a lower level of HDL-cholesterol (all p <
      0.05), whereas those with 0-1 vessel disease had a higher incidence of heavy
      smoking (73% vs 50%, p = 0.1) and a tendency to higher physical activity level at
      the onset (2.7 +/- 2.2 vs 2.4 +/- 2.3, NS). CONCLUSIONS: Young male patients with
      acute myocardial infarction may be characterized by 2 distinctive patterns: one
      associated with smoking and a higher physical activity level at the onset of
      acute myocardial infarction with 0-1 vessel disease and the other with
      hypertension and hypercholesterolemia with multivessel disease.

PMID- 10955252
TI  - [Coronary artery bypass grafting without cardiopulmonary bypass in 200 patients].
AB  - OBJECTIVES: To evaluate the efficacy of off pump coronary artery bypass grafting
      (CABG), results in the initial consecutive 200 patients were reviewed. METHODS:
      Between October 1996 and December 1999, 200 patients underwent CABG without
      cardiopulmonary bypass. There were 146 men and 54 women aged from 27 to 89 years
      (mean 68 years). Single, double, triple and left main disease were noted in 94,
      55, 33 and 18 patients, respectively, with a mean ejection fraction of 51%.
      Preoperative complications were previous stroke in 34 patients, chronic renal
      failure in 22 patients, previous CABG in 18 patients, and aortoiliac aneurysm or
      occlusive disease in 14 patients. Fifty-five patients (28%) were 75 years or
      older. Surgical approach was made through a midsternal incision including lower
      half small sternotomy in 105 patients, left anterior small thoracotomy in 92 and
      small epigastric incision (gastroepiploic-right coronary anastomosis) in 3. Mean
      number of distal anastomoses was 1.3 (range 1-4). Anastomosis was performed in
      189 left anterior descending, 13 diagonal, 27 circumflex and 41 right coronary
      arteries. The conduits were 174 internal thoracic, 10 internal thoracic-inferior
      epigastric composite, 22 right gastroepiploic and 5 radial arteries, and 50
      saphenous vein grafts. Four patients underwent combined off pump CABG and
      transmyocardial laser revascularization, and 36 patients underwent hybrid (off
      pump CABG and angioplasty) revascularization. RESULTS: Four patients (2.0%) died
      in the hospital due to intestinal necrosis in 2 patients, postoperative aortic
      dissection in one, and multiorgan failure with stroke in one. No serious
      ventricular tachyarrhythmia or use of intraaortic balloon pump occurred.
      Perioperative myocardial infarction was noted in one patient. Stroke occurred in
      4 patients (2.0%) but 3 patients recovered in a short period. Three-year survival
      and cardiac event free rate were 90.3% and 81.1% by the Kaplan-Meier method.
      Postoperative angiographic study showed excellent patent graft in 92% of grafts
      (192/209), stenosed (> or = 50%) graft in 5% (10/209) and occlusion in 3%
      (7/209). CONCLUSIONS: Off pump CABG can be performed safely and effectively in
      both high risk and low risk patients with coronary artery disease. Refinement of
      surgical technique and equipment will make this procedure more useful.

PMID- 10955253
TI  - Angiographic coronary morphology in patients with ischemic heart disease.
AB  - OBJECTIVES: To determine whether ischemia- or infarct-related arteries (IRAs) are
      accompanied by certain findings specific to clinical settings, coronary
      cineangiography was reviewed of 71 patients with stable effort angina pectoris
      (SAP), 72 with unstable angina pectoris (UAP), 118 with acute myocardial
      infarction (AMI) and 137 with old myocardial infarction (OMI). METHODS: The
      morphology of identifiable ischemia- or infarct-related lesions (IRLs) was
      classified as totally occlusive, and simple (Type I lesion) or complex (Type II
      lesion). Complex lesions were subdivided into Type IIa lesions (narrowing with
      irregular, poorly defined or hazy borders, sharp leading or trailing edges that
      overhang or are perpendicular to vessel walls, and globular endoluminal negative
      images), Type IIb (2 or more serial, closely spaced narrowings together with
      multiple irregularities), Type IIc (luminal narrowing with extraluminal contrast
      pooling, single or paired short thin linear radiolucencies with or without a
      variable degree of outpouching, and narrowing with definite outpouching with or
      without radiolucency), and Type IId (narrowing with morphology not included in
      Types IIa-IIc). RESULTS: Total occlusive lesions among identifiable IRLs occurred
      at 17 sites (23.9%) in patients with SAP, 7 (9.7%) with UAP, 48 (40.7%) with AMI
      and 30 (21.9%) with OMI. The mean diameter stenosis of identifiable IRLs was
      89.4% in patients with SAP, 92.0% with UAP, 93.1% with AMI, and 87.4% with OMI.
      Patent identifiable IRLs in patients with SAP had a significantly higher
      frequency of Type I lesions (29 sites, 40.8%) compared with those with UAP, AMI
      and OMI (p < 0.01), followed by a relatively lower occurrence of Types IIa 12
      (16.9%), IIb 8 (11.3%), IIc 3 (4.2%) and IId 2 (2.9%) lesions. Patients with UAP
      were characterized by a higher occurrence of Type IIa (34 sites, 47.2%, p < 0.01)
      and IIc (13 sites, 18.1%, p < 0.01) lesions compared with those with SAP.
      Patients with AMI had total occlusion (48 sites, 40.7%, p < 0.05) and Type IIa
      lesion (38 sites, 32.2%, p < 0.05) more frequently than those with SAP. Patients
      with OMI showed fewer total occlusions (30 sites, 21.9%), same occurrence of Type
      IIa lesion (39 sites, 28.5%), and higher occurrence of IIb (23 sites, 16.8%) and
      IIc (20 sites, 14.6%) than those with AMI. CONCLUSIONS: This analysis of coronary
      cineangiographies from patients with UAP, AMI and OMI, which share a common
      pathogenesis, shows that IRAs, especially IRLs, are associated with certain
      morphology specific to clinical settings, and that the morphology and severity of
      stenosis could change in a short period. The present results may improve coronary
      cineangiography interpretation about pathophysiological issues in vivo affecting
      coronary circulation.

PMID- 10955254
TI  - [Effect of radiofrequency catheter ablation on autonomic tone in patients with
      common atrial flutter: difference depending on the site of ablation].
AB  - OBJECTIVES: Radiofrequency catheter ablation (RFCA) of the inferior vena cava
      tricuspid annulus isthmus has become an effective procedure for radical treatment
      of common atrial flutter. This site is close to the right atrial posteroseptal
      region, so vagal denervation after slow pathway ablation in patients with
      atrioventricular nodal reentrant tachycardia can also occur after the procedure.
      To confirm this hypothesis, we tested whether autonomic disturbance can occur
      after RFCA in 16 patients with common atrial flutter. METHODS: Parameters of the
      autonomic function were measured using several components of the time domain
      analyses and power spectra of heart rate variability calculated from Holter
      recordings and the baroreflex sensitivity. Patients were divided into 2 groups
      based on the location of the ablated area: the isthmus group (9 patients) with
      the ablated area of the exact isthmus, and the posteroseptal group (7 patients)
      with the ablated area slightly shifted toward the right atrial posteroseptal
      position. All values after RFCA were compared with those before RFCA, and the
      ratio (after/before) was compared between the groups. The correlation between the
      ratio and cumulative delivered energy was also studied for each parameter.
      RESULTS: After RFCA, the heart rate increased, and the SD, rMSSD and pNN50
      decreased significantly in the posteroseptal group, whereas no significant
      changes occurred in the isthmus group. The high frequency of the power spectra
      decreased after RFCA only in the posteroseptal group, and the ratio was
      significantly smaller in the posteroseptal group compared to the isthmus group. A
      significant reverse correlation between the ratio of the high frequency and
      cumulative energy was observed only in the posteroseptal group. The baroreflex
      sensitivity tended to be diminished after RFCA only in the posteroseptal group.
      CONCLUSIONS: Vagal denervation can occur after RFCA of common atrial flutter when
      the ablation site is shifted toward the right atrial posteroseptal region.

PMID- 10955255
TI  - [Different inhibiting effects of abciximab and tirofiban on platelet thrombus
      formation on a collagen surface under flow conditions].
AB  - OBJECTIVES: Recently developed anti-GPIIb/IIIa agents effectively inhibit acute
      thrombotic occlusion of coronary arteries after interventional treatment, and
      have similar inhibiting effects on plasma ligand binding to GPIIb/IIIa. Clinical
      investigation has revealed that abciximab, the chimeric monoclonal antibody
      against GPIIb/IIIa, has superior in vivo antithrombotic effects to other agents.
      The inhibiting effects of abciximab and another anti-GPIIb/IIIa agent, tirofiban,
      were investigated on platelet thrombus formation on a collagen surface under flow
      conditions. METHODS: Blood was drawn from 6 normal volunteers and anticoagulated
      with a specific inhibitor of thrombin, argatroban, at a final concentration of
      100 microM. Platelets were rendered fluorescent by addition of mepacrine to a
      final concentration of 10 microM. Mepacrine is concentrated in the dense granules
      of platelets and leukocytes, but does not accumulate in red blood cells, so
      platelet thrombi can be detected by fluorescence microscopy even in the presence
      of red blood cells. Horizontal glass slips covered with fibrillar type I collagen
      were assembled in a Hele-Shaw type flow chamber. RESULTS: Platelet thrombi were
      developed on the collagen surface even in the absence of platelet activating
      agents. Both abciximab and tirofiban inhibited the platelet thrombus formation.
      Single platelet adhesion on the collagen surface was inhibited only by abciximab
      and not by tirofiban. CONCLUSIONS: The superior in vivo antithrombotic effects of
      abciximab may be partially explained by its inhibiting effects on the platelet
      adhesion on exposed subendothelial matrix.

PMID- 10955256
TI  - [Impending paradoxical embolism visualized by echocardiography combined with
      pulmonary embolism: a case report].
AB  - A 43-year-old man was admitted to our hospital complaining of dyspnea on exertion
      and dizziness. Transthoracic echocardiography revealed a mobile mass (3.5 x 1.0
      cm) attached to the left atrial septum and transesophageal echocardiography
      showed the mass in the right atrium protruding through the patent foramen ovale
      into the left atrium. A mobile snake-like thrombus was apparent in the right
      atrium and right ventricle. The diagnosis was pulmonary embolism with impending
      paradoxical emboli.

PMID- 10955257
TI  - Slowly growing cardiac tumor: a case of fibroelastoma.
AB  - Echocardiographic follow-up for 16 years in an asymptomatic patient with mitral
      stenosis showed very slow growth of a mass attached to the mitral valve. The
      tumor doubling time was estimated to be 3.6 years. Surgical excision of the mass
      was performed when the patient eventually developed dyspnea on exertion, and
      histopathological examination revealed papillary fibroelastoma. Echocardiographic
      follow-up and anti-coagulation may be sufficient treatment for asymptomatic
      patients with papillary fibroelastoma.

PMID- 10955258
TI  - [A 31-year-old woman complaining of hemosputum. Systemic arterial supply to the
      basal segments of the lung].

PMID- 10955259
TI  - [A 66-year-old man with aphasia and right hemiplegia. Swiss cheese-like
      resolution of left atrial thrombus].

PMID- 10955260
TI  - No incision is even better than minimal incision cardiac surgery for atrial
      septal defects.

PMID- 10955262
TI  - The Finnish sauna bath and its use in patients with cardiovascular disease.
AB  - The Finnish tradition of sauna bathing is meant to be an experience in
      relaxation, and the length of time spent in the sauna and the preferred
      temperature vary considerably among individuals. The pleasures of sauna bathing
      can be considered safe and without undue risk of cardiac complications even for
      CVD patients, providing bathing is conducted sensibly for an appropriate period
      of time, and extremes in temperature are voided.

PMID- 10955261
TI  - Tobacco dependence treatment in patients with heart and lung disease:
      implications for intervention and review of pharmacological therapy.

PMID- 10955263
TI  - Effect of pulmonary rehabilitation on quality of life in patients with COPD: the
      use of SF-36 summary scores as outcomes measures.
AB  - PURPOSE: Pulmonary rehabilitation (PR) is an accepted therapy for patients with
      chronic obstructive pulmonary disease (COPD), improving both exercise capacity
      and quality of life (QOL). Generic measures of QOL have been criticized as being
      insensitive to detecting the improvement in QOL after PR in contrast to disease
      specific instruments. The authors looked at the Medical Outcomes Survey Short
      Form 36-item questionnaire (SF-36), a generic QOL measure, to detect changes in
      QOL in COPD patients after completion of PR. METHODS: Patients with COPD who
      participated in a PR program completed the QOL questionnaire before and after
      completion of PR. Exercise tolerance was assessed by the 6-minute walking test.
      Quality of life was assessed by the SF-36; the authors calculated its eight
      dimensions as well as mental (MCS) and physical (PCS) component summary scores.
      RESULTS: The patients realized a significant improvement in exercise tolerance; 6
      minute walking test distance increased from 470 +/- 104 m (mean +/- standard
      deviation) to 536 +/- 133 m (P = 0.0006) after PR. Quality of life also improved
      in nearly all dimensions and in both summary scores; PCS improved from 26.1 +/-
      8.0 before PR to 30.5 +/- 9.0 after PR (P = 0.008) and MCS improved from 27.9 +/-
      7.0 before PR to 34.1 +/- 5.0 after PR (P = 0.0002). CONCLUSION: The SF-36 and
      its summary scores are sensitive instruments to detect improvement in QOL in COPD
      patients after PR.

PMID- 10955264
TI  - Disparate effects of improving aerobic exercise capacity and quality of life
      after cardiac rehabilitation in young and elderly coronary patients.
AB  - PURPOSE: Although cardiopulmonary exercise variables predict prognosis,
      functional capacity, and quality of life (QoL) in patients with coronary artery
      disease (CAD), these variables have not been assessed fully before and after
      exercise training in elderly with CAD. Therefore, the purpose of this study was
      to determine the impact of formal Phase II cardiac rehabilitation and exercise
      training programs on cardiopulmonary variables and QoL in elderly and younger CAD
      patients. METHODS: The authors analyzed consecutive patients before and after
      Phase II cardiac rehabilitation and exercise training programs, and compared
      exercise cardiopulmonary data and data from validated questionnaires assessing
      QoL (MOS SF-36) and function in 125 younger patients (< 55 years; mean 48 +/- 6
      years) and 57 elderly (> 70 years; mean 78 +/- 3 years). RESULTS: At baseline,
      elderly patients had lower estimated aerobic exercise capacity (-27%; P < 0.001),
      peak oxygen consumption (VO2) (-19%; P < 0.01), and anaerobic threshold (-10%; P
      < 0.05), as well as total function scores (-11%; P < 0.01) and total QoL scores (
      5%; P = 0.06). Commonly used prediction equations greatly overestimated aerobic
      exercise capacity compared with precise measurements using cardiopulmonary
      testing both before (+23% and +12% in younger and elderly patients, respectively)
      and after the exercise training programs (+51% and +31% in younger and elderly
      patients, respectively), and more so in younger compared with older patients.
      After rehabilitation, the elderly had significant improvements in estimated
      aerobic exercise capacity (+32%; P < 0.0001), peak VO2 (+13%; P < 0.0001),
      anaerobic threshold (+11%; P = 0.03), total function scores (+27%; P < 0.0001),
      and total QoL scores (+20%; P < 0.0001). Although younger patients had greater
      improvements in estimated aerobic exercise capacity (+44% versus +32%; P = 0.08),
      peak VO2 (+18% versus +13%; P < 0.01), and anaerobic threshold (+17% versus +11%;
      P = 0.07), the elderly had statistically greater improvements in both function
      scores (+27% versus +20%; P = 0.02), and total QoL scores (+20% versus +14%; P =
      0.03). CONCLUSIONS: These data confirm the benefits of precisely determining
      aerobic exercise capacity by cardiopulmonary function, especially to determine
      the benefits of an exercise training program. In addition, these data using
      cardiopulmonary exercise tests and validated assessments of quality of life
      demonstrate the disparate effects of cardiac rehabilitation programs on
      improvements in aerobic exercise capacity and QoL in young and elderly with CAD.

PMID- 10955265
TI  - Barriers to outpatient cardiac rehabilitation participation and adherence.
AB  - BACKGROUND: A significant proportion of eligible patients do not participate in
      outpatient cardiac rehabilitation. The purpose of this study was to identify
      barriers to participation and adherence to outpatient cardiac rehabilitation by
      querying program staff. METHODS: In January 1999, a survey was mailed to all
      North Carolina program directors of outpatient cardiac rehabilitation programs.
      The response rate was 85% (61/72). RESULTS: Across programs, the most common
      barrier to participation in outpatient cardiac rehabilitation was financial.
      Other barriers identified by program directors included lack of patient
      motivation, patient work or time conflicts, and lack of physician support or
      referral. When program directors were asked to cite reasons that referred
      patients provided for not participating in rehabilitation, the most common answer
      was financial or lack of motivation or commitment. The most common reason cited
      for dropping out of the rehabilitation program was work, followed by financial
      reasons and lack of motivation or commitment. CONCLUSIONS: The results of this
      statewide survey of program directors indicated a common set of barriers that
      many patients currently face to begin and continue participating in outpatient
      cardiac rehabilitation.

PMID- 10955266
TI  - The major components of human energy balance during chronic beta-adrenergic
      blockade.
AB  - PURPOSE: The authors compare the major components of energy balance--dietary food
      intake, resting metabolic rate, and physical energy expenditure--in patients
      receiving beta-blocking medications and healthy controls. METHODS: The authors
      recruited subjects who were receiving beta-blocking agents (n = 22) from local
      hospitals and clinics. Twenty-two healthy controls were matched to each patient
      based on age, weight, and gender. Resting metabolic rates were determined using
      indirect calorimetry. Three-day dietary intakes and physical activity assessments
      were analyzed. RESULTS: There were no between-group differences in calories
      ingested or self-reported physical activity patterns. However, resting metabolic
      rates were lower in the beta-blocked subjects (beta-blocked = 1,541 +/- 464
      kcals/day; controls = 1,817 +/- 426 kcals/day; P < 0.05). CONCLUSIONS: beta
      adrenergic blockade causes a reduction in resting metabolic rate. Therefore, beta
      blocked individuals should increase physical activity, decrease dietary intake,
      or both to maintain daily energy balance and prevent weight gain that accompanies
      a reduction in metabolic rate.

PMID- 10955267
TI  - A survey of exercise testing: methods, utilization, interpretation, and safety in
      the VAHCS.
AB  - BACKGROUND: Healthcare organizations are being graded in terms of their adherence
      to practice guidelines. The authors sought information on practice patterns of
      exercise testing within the Veterans Affairs Health Care System (VAHCS) to
      determine how well current practice patterns adhere to current guidelines. In
      addition, we sought to update past surveys to determine methods, indications,
      utilization of alternative diagnostic modalities, criteria for interpretation,
      safety, and physician supervision of exercise testing within the VAHCS. METHODS:
      Questionnaires were sent to 72 of the largest Veterans Affairs Medical Centers
      with cardiology divisions. The centers were queried regarding volume and type of
      exercise testing (standard, nuclear, and echocardiographic), indications, safety,
      protocols used, and criteria for interpretation. RESULTS: Seventy-one
      questionnaires were returned, comprising a total of 75,828 exercise tests
      performed within the last year. Virtually all indications for exercise testing
      fit the American Heart Association/American College of Cardiology (AHA/ACC)
      guidelines Class I criteria; 46% of patients were tested for the evaluation of
      chest pain; 14% were tested to evaluate patients at high risk for coronary artery
      disease; 10% were preoperative evaluations; and 8% were post-myocardial
      infarction evaluations. The most commonly used diagnostic test was the standard
      exercise electrocardiogram; a patient was five times more likely to undergo a
      standard exercise electrocardiogram or nuclear exercise test than an exercise or
      pharmacologic echocardiogram. The largest proportion of centers (49%) used 1.0-mm
      horizontal or downsloping ST depression as a criterion for an abnormal test,
      although 22% considered 1.5-mm upsloping ST depression to be abnormal, and 25%
      relied on a treadmill score. Seventy-eight percent of respondents used the
      treadmill, and of these, 82% used the Bruce or modified Bruce protocol. Four
      major cardiac events were reported (three myocardial infarctions, one sustained
      ventricular tachycardia) representing an event rate of 1.2/10,000. A physician
      was present during 73% of all standard exercise tests; 21% of respondents
      reported that a physician was required to be present "only for high-risk
      patients." CONCLUSION: Indications for exercise testing are in close agreement
      with the AHA/ACC guidelines; thus, the test continues to have an important role
      in diagnosis and prognosis among patients with or suspected of having coronary
      artery disease. The exercise test is an extremely safe procedure, with an event
      rate similar to other recent surveys. However, a great deal of variation exists
      in terms of criteria for abnormal results and whether physician presence is
      required during exercise testing.

PMID- 10955268
TI  - Safety and efficacy of exercise training in a patient awaiting heart
      transplantation while on positive intravenous inotropic support.
AB  - The safety and efficacy of exercise training in patients with congestive heart
      failure (CHF) is well established; however, the impact that exercise has on the
      subgroup of CHF patients awaiting heart transplant while on intravenous positive
      inotropic support remains largely unreported. This case study describes the
      safety and efficacy of exercise training in a patient awaiting heart transplant
      while on intravenous milrinone. Over a 1.2-year period, 246 exercise sessions
      were conducted with a total of 180.15 hours of aerobic exercise. During that
      time, the patient experienced only one hypotensive episode during exercise and
      had no other adverse events. The patient demonstrated a 38% increase in aerobic
      exercise time and a 34% increase in sustainable exercise workload. Research is
      needed to demonstrate the positive impact of exercise training on this subgroup
      of CHF patients.

PMID- 10955269
TI  - Depression: the forgotten diagnosis among hospitalized adults.
AB  - Depression, one of the most frequent of all medical disorders, is an illness that
      often concomitantly occurs with many other diseases in hospitalized adult
      patients. Sadly, overwhelming evidence suggests that comorbid depression is
      commonly misdiagnosed, undertreated, or not diagnosed at all when present in
      critically ill patients. While safe, modern, and cost-effective treatments are
      available for treating this disorder, comorbid depression remains a silent and
      unseen illness adversely affecting patient outcomes. With an understanding that
      this pernicious underlying illness frequently exists in hospitalized adults,
      nurses can identify the symptoms and patterns of comorbid depression, thereby
      being extremely effective in decreasing the morbidity and mortality that often
      accompanies this forgotten diagnosis.

PMID- 10955270
TI  - Stroke-specific FIM models in an urban population.
AB  - Data from the Functional Independence Measure (FIM) are important outcome
      measures in the stroke population undergoing rehabilitation. The FIM consists of
      18 scales scored from 1 to 7; higher numbers mean greater ability. Several
      different scores can be obtained from the FIM: a total score (sum of all the
      scales), individual scale scores, and a physical and cognitive score (a two
      dimensional interpretation). Research has shown that FIM data can have
      multidimensional components. That implies different groupings of scales may exist
      and with this the possibility of developing more sophisticated and robust
      measures within stroke populations. This study examined the multidimensional
      aspects of FIM using an urban sample of ischemic and hemorrhagic stroke patients.
      We found a three-dimensional FIM solution for both stroke groups that included
      self-care, cognitive function, and toileting as the major grouping of scales.
      These findings confirm a multidimensional nature of FIM scores and show a
      condition-specific pattern of FIM scores in stroke patients. This knowledge will
      help nurses, clinicians, and researchers develop more sensitive ways of recording
      care outcomes; improved prediction of stroke outcomes may also emerge from this
      knowledge.

PMID- 10955271
TI  - Living in limbo: the low-level brain-injured patient and the patient's family.
AB  - One hallmark of severe traumatic brain injury (TBI) is a loss of consciousness
      followed by varying states of consciousness. Estimates suggest that 30-40% of
      individuals who survive severe TBI will stay in low-level or reduced states of
      consciousness for prolonged periods. The state of coma is relatively easy to
      diagnose; however, differential diagnosis of other states of reduced
      consciousness have proven to be much more difficult, precipitating a number of
      problems related to prognosis, treatment, and rehabilitation. Accurate diagnosis
      is critical in determining the prognosis for persons with severe TBI because it
      has significant implications for the patient, family, clinician, and payer.
      Studies have shown that prognosis directly influences numbers and types of
      treatments recommended. Often, families find themselves being forced to make
      critical decisions with little knowledge and a great deal of uncertainty.
      Understanding reduced states of consciousness and facilitating accurate
      evaluation of such states allow neuroscience nurses to help families effectively
      cope during this difficult time.

PMID- 10955272
TI  - Evaluation of seizure observation and documentation.
AB  - This study evaluated seizure documentation after participants observed videotaped
      seizures to determine how their background (educational level, employment
      position, years of experience, practice frequency, and familiarity with epilepsy
      and seizures) and attributes of the seizures themselves affected their skill.
      Observer variables did not show significant differences when mean seizure rating
      scores of 348 documented seizures for 58 participants were compared. Combinations
      of variables were significant; certified nursing assistants (CNAs) with clinical
      seizure experience had significantly higher mean seizure rating scores than those
      without experience (p < .01). There were significant differences in the mean
      percentile scores for each seizure observed (p < .001). Seizures with excess
      motor activity had the highest scores. Most common observations for any seizure
      observed were location and description of movement. Participants had
      significantly higher scores when observing a seizure a second time (p < .001).
      Differences in education, employment position, and years of employment are not
      limiting factors in performing seizure observation and documentation for persons
      who have been trained and certified in the skill. Opportunities to periodically
      view seizures improved seizure observation and documentation. Because motor
      movement observations predominate seizure documents, seizure observation
      instruction should not only emphasize key observational details but also
      highlight less frequent observations, such as responsiveness, that may play a key
      role in seizure classification. Using videotaped seizures and a scoring tool are
      useful for initial training and certification as well as periodic retraining to
      maintain quality in the skill.

PMID- 10955274
TI  - The pathophysiology of demyelination and the ionic basis of nerve conduction in
      multiple sclerosis: an overview.
AB  - Multiple sclerosis (MS) affects young adults during the prime of life,
      complicating child-rearing and work-related activities, often resulting in
      significant disability. New treatment options are rapidly becoming available.
      Persons with MS and their families rely on nurses to provide current and accurate
      information. Neuroscience nurses are increasingly challenged to keep abreast of
      new treatments and research and the scientific bases for them. In response to
      this need, nurses must develop a basic understanding of the proposed etiology of
      MS as well as of the pathophysiology of demyelination and the ionic basis of
      nerve conduction.

PMID- 10955273
TI  - 'What happened to me': rural African American elders' experiences of stroke.
AB  - The purpose of this descriptive, qualitative study was to examine the experience
      of stroke from the perspective of rural African American elders and their family
      members. The qualitative method of narrative analysis was used to explain the
      stroke experience from the perspective of the participants. Descriptive narrative
      analysis was used to produce a report of the interpretive schemes that study
      participants used to create the significance of past events and to anticipate the
      consequences of future actions in regard to the stroke experience. The findings
      revealed five themes: Discovering Stroke, Delaying Treatment, Living with
      Uncertainty, Discovering the Impact of Stroke, and Reconstructing Life. The
      findings from this study have implications for both nursing practice and nursing
      research. First, the themes and patterns that resulted from the narrative
      analysis highlight issues of how, when, and why rural African American elders
      seek treatment for stroke symptoms. This information can assist practicing nurses
      in educating this target group on signs and symptoms of stroke, stroke
      prevention, and the emergent nature of stroke. Second, the study contributes
      significantly to understanding how individuals and their families live through
      and respond to the experience of stroke.

PMID- 10955275
TI  - Exploring the guidelines for the management of severe head injury.
AB  - A significant improvement in patient outcomes can be achieved by in-hospital
      interventions aimed at the prevention of secondary brain injury. The Guidelines
      for the Management of Severe Head Injury is a scientific, evidence-based document
      that evaluates the current evidence for practice and interventions to reduce
      secondary brain injury and improve outcome for traumatic brain injury (TBI)
      patients. The Guidelines covers a wide range of topics including trauma systems,
      oxygenation and blood pressure resuscitation, intracranial pressure monitoring,
      intracranial hypertension, nutrition, and pharmacological interventions for the
      severe TBI patient in the intensive care environment. Head injury care requires
      an interdisciplinary approach involving emergency room personnel, trauma nurses,
      and critical care nurses. Critical care nurses will find this document especially
      applicable because secondary brain injuries are often the result of events that
      occur in the ICU setting: hypoxemia, hypotension, and intracranial hypertension.

PMID- 10955276
TI  - Oral glucose tolerance is unaltered in vitamin D-deficient rat.
AB  - Vitamin D deficiency has been reported to result in impaired glucose tolerance
      and decreased insulin secretion when glucose is administered either intravenously
      or intraperitoneally. The aim of the present study was to study oral glucose
      tolerance and glucose absorption in a vitamin D-deficient rat model. Oral glucose
      tolerance tests were carried out in vitamin D-deficient and control rats, and
      this was found to be unaltered in the deficient state. Intestinal absorption of
      glucose was drastically reduced in the deficient animal and was found to be due
      to a reduction in the sodium-dependent component of glucose transport. Thus the
      unaltered oral glucose tolerance in the vitamin D-deficient rat is probably due
      to impaired absorption of glucose.

PMID- 10955277
TI  - Vitamin E level changes in serum and red blood cells due to acute exhaustive
      exercise in collegiate women.
AB  - The purpose of this study was to investigate the change in vitamin E level in
      both serum and red blood cells (RBC) during exercise and to clarify the effect of
      vitamin E supplementation. Ten young sedentary female subjects received 200 mg D
      alpha-tocopherol acetate daily for 1 wk after the initial exercise bout. After 1
      wk of vitamin E supplementation, the same subjects repeated the same exercise.
      Before vitamin E supplementation, the alpha-tocopherol level in the serum (serum
      alpha-tocopherol) did not change after exercise, but a significant decrease in
      the alpha-tocopherol level in RBC (RBC-alpha-tocopherol) was observed after
      exercise (p < 0.05). On the other hand, after vitamin E supplementation, the
      serum-alpha-tocopherol level decreased significantly after exercise (p < 0.05),
      while the RBC-alpha-tocopherol level was maintained after exercise. Furthermore,
      a negative correlation between the changes in serum- and RBC-alpha-tocopherol
      levels was observed only after vitamin E supplementation (r = 0.667, p < 0.05).
      The present results suggest that as RBC suffers oxidative stress, vitamin E in
      RBC is consumed to protect RBC from oxidative damage during exercise. These
      results also suggest that when there is a sufficient amount of vitamin E in the
      serum, vitamin E is shifted from the serum to RBC, resulting in a steady RBC
      alpha-tocopherol level and a decrease in the serum-alpha-tocopherol level under
      oxidative stress such as exercise.

PMID- 10955278
TI  - Study of industrial microencapsulated ferrous sulfate by means of the
      prophylactic-preventive method to determine its bioavailability.
AB  - Radio-iron tests are frequently used to measure the bioavailability of different
      iron sources for food fortification. As the labeling procedures must be done
      under laboratory conditions, complementary studies should be carried out to
      evaluate the bioavailability of iron sources produced on an industrial scale. The
      iron bioavailability of SFE-171 (ferrous sulfate microencapsulated with
      phospholipids) was studied in previous reports using the compounds labeled with
      59Fe and 55Fe; the results showed an iron bioavailability similar to that of
      ferrous sulfate. In the present work, the iron bioavailability of industrial SFE
      171 was studied by the prophylactic-preventive method in rats using ferrous
      sulfate as the reference standard. Elemental iron powder was also studied by the
      same method for comparative purposes. The liver iron concentration of each animal
      was determined at the end of the experiment in order to evaluate the influence of
      each iron source on the liver iron stores. Relative biological values of 98 and
      34% were found for SFE-171 and elemental iron powder, respectively, while the
      corresponding relative liver iron concentrations were 104 and 45%. The results
      provided by the prophylactic-preventive method show that the iron bioavailability
      of industrial SFE-171 is similar to that of ferrous sulfate; these results are
      also in agreement to those obtained with the radioactive compounds. We can
      conclude that the SFE-171 obtained by industrial procedures for massive use in
      iron food fortification has the same bioavailability as that of the SFE-171
      produced and labeled under laboratory conditions.

PMID- 10955280
TI  - Effect of oxidized frying oil and vitamin C levels on the hepatic xenobiotic
      metabolizing enzyme system of guinea pigs.
AB  - The influence of oxidized frying oil (OFO) on the guinea pig hepatic microsomal
      xenobiotic-metabolizing enzyme system in the presence of different amounts
      dietary vitamin C was investigated. Weanling male guinea pigs were divided into
      four groups and were fed 15% oxidized frying oil diets supplemented with vitamin
      C at 300, 600, or 1,500 mg/kg (experimental diets) or a control diet that
      contained 15% fresh untreated soybean oil with 300 mg/kg of vitamin C,
      respectively. After 60 d, guinea pigs were euthanized and phase I and phase II
      xenobiotic-metabolizing enzymes in the liver were determined. Compared with the
      fresh oil diet fed the control group, the relative liver weight was higher in the
      OFO-fed groups. Hepatic microsomal protein and cytochrome P450 contents were
      significantly higher in OFO-fed guinea pigs than in the control group. Both
      values increased in response to increased intake of vitamin C. The activities of
      phase II relative components, including UDP-glucuronyl transferase, UDP
      glucuronyl dehydrogenase and beta-glucuronidase, of guinea pigs fed the OFO diets
      supplemented with 300 mg vitamin C/kg were significantly higher than those of
      guinea pigs fed the control diet. However, the phase II relative components
      decreased with increasing vitamin C content in the diet. The results demonstrate
      that both dietary OFO and vitamin C in guinea pigs induce hepatic xenobiotic
      metabolizing enzymes, but the level of induction is modulated by the dietary
      vitamin C level.

PMID- 10955279
TI  - Synergistic effects of food colors on the toxicity of 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1) in primary cultured rat hepatocytes.
AB  - The synergistic effect of food additives or food colors on the toxicity of 3
      amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was investigated using
      primary cultured rat hepatocytes. When hepatocytes from rats fed a standard diet
      were treated with a mixture of four major food additives (sorbitol, sodium L(+)
      glutamate, benzoic acid, and propylene glycol) or a mixture of six typical
      artificial food colors (erythrosine, allura red, new coccine, brilliant blue,
      tertrazine, and fast green), the in vitro treated food-color mixture itself
      showed cytotoxicity: the reduction of cell viability and decreases in the
      activities of gluconeogenesis and ureogenesis. The food-color mixture enhanced
      cytotoxicity of Trp-P-1 obviously. We then investigated the effects of in vivo
      dosed food additives or food colors on Trp-P-1-caused toxicity. Hepatocytes were
      isolated and cultured from rats fed a diet containing a mixture of food additives
      or a mixture of food colors with half the amount of their respective acceptable
      daily intake for 4 wk. Trp-P-1 was administered to the hepatocytes at various
      concentrations for 12 h. Synergistic effects of in vivo-dosed food additives and
      food colors were not observed on Trp-P-1-caused cytotoxicity as estimated by a
      loss of cell viability and the reductions of DNA and protein syntheses. On the
      contrary, we have observed that in vivo administered food colors synergistically
      facilitated to reduce the activities of gluconeogenesis and ureogenesis in Trp-P
      1-treated hepatocytes. These results suggest that the daily intake of artificial
      food colors may impair hepatic functions such as gluconeogenesis and ureogenesis,
      when dietary carcinogens are exposed to the liver cells.

PMID- 10955281
TI  - Selective uptake of dietary tocotrienols into rat skin.
AB  - Using a vitamin E mixture extracted from palm oil, the tissue distribution of
      dietary tocotrienols and tocopherols was examined in rats and mice. Wistar rats
      (4-wk-old) were fed a diet containing 48.8 mg/kg alpha-tocopherol, 45.8 mg/kg
      alpha-tocotrienol and 71.4 mg/kg gamma-tocotrienol for 8 wk. Nude mice (BALB/c
      Slc-nu, 8-wk-old) and hairless mice (SKH1, 8-wk-old) were fed the same diet for 4
      wk. alpha-Tocopherol was abundantly retained in the skin, liver, kidney and
      plasma of rats and mice. alpha-Tocotrienol and gamma-tocotrienol were detected
      slightly in the liver, kidney and plasma, while substantial amounts of these
      tocotrienols were detected in the skin of both rats and mice. The present study
      suggests that the skin is a unique tissue in respect to its ability to
      discriminate between various vitamin E analogs.

PMID- 10955283
TI  - Is there life without mother?
AB  - Clinical and literary materials are presented to illustrate the compulsive need
      some children (frequently abused and/or deprived ones) continue to feel as they
      grow up for submission to and identification with the earliest parental figure.
      Intrapsychic loss is threatened by intense murderous hatred felt toward a parent
      without whom the child's survival is not possible. Conflicts over sadomasochistic
      fantasy, feeling, and action are used to hold on to the parent within and without
      the mind, and these can dominate the child's life.

PMID- 10955282
TI  - Increases in gastric histidine decarboxylase activity and plasma gastrin level in
      streptozotocin-induced type 1 diabetic rats.
AB  - When type 1 diabetes mellitus was induced in rats by injecting streptozotocin,
      histidine decarboxylase expression was abnormally up-regulated in a
      transcriptional level, and 7 d after the injection, the enzyme activity was
      increased about 3-fold over the control (p < 0.05). When the diabetic rats were
      administered with insulin for 3 d, the increased histidine decarboxylase activity
      returned to a normal level in addition to normalization of the plasma glucose
      level. The plasma gastrin level in the fasting state was also significantly
      elevated in the diabetic rats, and the insulin treatment normalized the level. In
      the diabetic rats, fasting gastric acid output increased significantly and
      gastric pH was lowered. These results suggest that the gastric histidine
      decarboxylase activity and plasma gastrin level are increased in connection with
      the depletion of insulin in streptozotocin-induced diabetic rats, and gastric
      acid secretion is stimulated at a basal level, presumably due to increases in the
      concentrations of histamine and gastrin in oxyntic mucosa.

PMID- 10955284
TI  - The mother within the mother.
AB  - This paper describes the subjective experience of internalization, focusing on
      the daughter's inner world as the encounters becoming and being a mother. Three
      case vignettes at three phases of a woman's mothering cycle are used to
      demonstrate modes of registration and expression of her own internalized mother
      as these in turn involve her offspring. Some issues in analyzing the new mother
      are raised by the material, as well as implied questions about how "mothering"
      behaviors emerge at later junctures.

PMID- 10955286
TI  - Sadomasochistic relating: what's sex got to do with it?
AB  - The sexuality in sadomasochistic relating is most often viewed as defensive,
      functioning to erotize the repetition of earlier trauma, as a defense against
      painful affect, or as masking early, nonerotic needs for recognition and
      autonomy. However, this emphasis on the nonerotic dimension of so-called
      sexualized experience leads to symbolic interpretations of sexuality; this
      "deliteralization of sexuality" requires some embodiment in the concrete and
      literal, or metaphor is delinked from that which it is derived. Without
      discounting the validity of such formulations, this paper aims to put the drive
      (libido) back into formulations of sadomasochistic relations, and discusses the
      erotic dimension in sadomasochistic relations as an irreducible, hidden structure
      that both threatens and sustains the destructive attachment. It is suggested that
      sexuality is a driving force behind sadomasochistic interplay, while aggression
      may be recruited for defensive, concealing purposes. Through a case illustration,
      this paper demonstrates how sadomasochistic relating is symbolically penetrating,
      teasing, withholding, and intensifying in hate-inducing ways, all of which are
      designed to gratify and simultaneously harden the other. In many cases,
      sadomasochistic sexuality may be viewed as aggressivized, paradoxically, to
      maintain safety under the regressive pull of sexual and preoedipal longings.

PMID- 10955285
TI  - On trying something new: effort and practice in psychoanalytic change.
AB  - This paper describes one of the ingredients of successful psychoanalytic change:
      the necessity for the analysand to actively attempt altered patterns of thinking,
      behaving, feeling, and relating outside of the analytic relationship. When
      successful, such self-initiated attempts at change are founded on insight and
      experience gained in the transference and constitute a crucial step in the
      consolidation and transfer of therapeutic gains. The analytic literature related
      to this aspect of therapeutic action is reviewed, including the work of Freud,
      Bader, Rangell, Renik, Valenstein, and Wheelis. Recent interest in the complex
      and complementary relationship between action and increased self-understanding as
      it unfolds in the analytic setting is extended beyond the consulting room to
      include the analysand's extra-analytic attempts to initiate change. Contemporary
      views of the relationship between praxis and self-knowledge are discussed and
      offered as theoretical support for broadening analytic technique to include
      greater attention to the analysand's efforts at implementing therapeutic gains.
      Case vignettes are presented.

PMID- 10955287
TI  - Brief communication: evenly hovering attention.

PMID- 10955288
TI  - Brief communication: playing games versus being fooled.

PMID- 10955289
TI  - [Imaging technics in diseases of the pharynx--the expectations and requirements
      of the clinician].
AB  - Pathological conditions of the pharynx requiring diagnostic imaging (CT and/or
      MRI) are in increasing frequency malformations, inflammation, trauma, dysphagia
      and neoplasia. For neoplastic diseases CT/MRI are of major importance for
      pretherapeutic staging. Furthermore they should be used routinely in tumor follow
      up. Primary goal of diagnostic imaging of the pharynx is the analysis of
      submucosal structures that are not visible by clinical means. The close
      cooperation between otorhinolaryngology and radiology is necessary to define
      size, extent of tumor spread, infiltration and/or destruction of vital structures
      (vessels, nerves), leading to an individual therapeutic regimen.

PMID- 10955290
TI  - [The pharynx. The imaging of its normal anatomy].
AB  - BACKGROUND: The pharynx, being part of the digestive as well as the respiratory
      system, is embedded in the complex spatial anatomy of the neck and, due to its
      function and location, represents a very sophisticated region. DIAGNOSIS: Cross
      sectional imaging with CT and MR imaging plays an indispensable complementary
      role to clinical work-up, as far as submucosal and deep cervical spaces are
      concerned. However, as dysphagia is a common symptom in clinical practice,
      interpretation of double contrast studies and videofluoroscopic investigations
      are also on frequent demand in the daily routine. CONCLUSION: Close
      interdisciplinary co-operation and the radiologist's familiarity with the anatomy
      of the region are required in order to use the diagnostic tools in an optimal
      fashion.

PMID- 10955291
TI  - [Congenital and benign changes with regard to the pharynx].
AB  - DEVELOPMENT: The first part of this article is supposed to present a brief
      overview on the development of tissues and structures related to the pharynx, as
      far as they provide a better understanding of the most congenital lesions in this
      area of the body. BENIGN LESIONS: The second part of this article focuses on
      benign lesions originating in the pharynx or in neighbouring structures.
      Functional pharynx abnormalities are beyond the scope of this paper.

PMID- 10955293
TI  - [Malignant tumors of the pharynx].
AB  - BACKGROUND: Malignant tumors of the head and neck region are amongst the six most
      often occurring tumors of the body. They can be associated with the different
      anatomical compartments as well as different histologic types. The way of tumor
      spread of these malignancies depends on their histologic type and on the region.
      These compartments can be separated into the nasopharynx, the oropharynx, and the
      hypopharynx. Most of the malignant tumors belong to the squamous cell carcinomas,
      other histologic types are depicted less frequently. The histologic types of the
      other groups which are seen more often comprise of lymphomas and adenoid cystic
      carcinomas. The undifferentiated carcinoma of the nasopharynx is supposed to be a
      special type of tumor. The malignant tumors of the pharynx can also involve all
      three compartments. Beside these tumors, malignancies of mesenchymal origin can
      also be delineated. IMAGING MODALITIES: The imaging modalities most frequently
      used to detect these tumors and to clarify their extension are contrast enhanced
      computed tomography, magnetic resonance imaging, nuclear-medicine imaging
      modalities such as positron emission tomography. Other scintigraphic imaging
      methods play a less important role. CONCLUSION: The different imaging modalities
      of malignant pharyngeal tumors and of potentially infiltrated lymph nodes with
      the weightness on computed tomography and magnetic resonance imaging and their
      appearance in these imaging techniques shall be enhanced in this paper.

PMID- 10955292
TI  - [Inflammatory diseases of the pharynx. The imaging findings and diagnostic
      strategy].
AB  - PURPOSE: To demonstrate imaging findings in inflammatory diseases of the pharynx
      and possible complications. MATERIAL AND METHODS: Radiologic imaging of the
      pharynx is based on the use of conventional X-ray films, computed tomography and
      magnetic resonance imaging, plain and contrast enhanced. RESULTS: The advantages
      of cross sectional imaging techniques like CT and MRT lie in the possibility to
      diagnose submucosal disease and localized as well as general complications. Most
      frequently abscesses and phlegmonous diseases have to be diagnosed. CT proves
      advantageous due to its fast imaging protocol and the widely availability. MRI is
      superior due to its superior soft tissue contrast and the multiplanar imaging.
      CONCLUSION: Spiral-CT and MRI mean valuable diagnostic tools for the evaluation
      of inflammatory diseases of the pharynx and possible complications.

PMID- 10955294
TI  - [The value of spiral CT in the staging of carcinomas of the oral cavity and of
      the oro- and hypopharynx].
AB  - PURPOSE: To compare spiral and conventional CT in the staging of carcinomas of
      the oral cavity, the oropharynx and hypopharynx. METHOD: Retrospectively 101
      conventional CTs and prospectively 107 spiral CTs were analyzed regarding to
      correct T and N staging. CT results were compared with histological staging.
      RESULTS: In conventional CT, there were correctly staged 85% of T stages (T1 62%,
      T2 74%, T3 81%, T4 94%) and 85% of N stages (N0 79%, N1 71%, N2 89%, N3 94%).
      Spiral CT showed correct results in 84% of T stages (T1 67%, T2 74%, T3 88%, T4
      95%) and in 86% of N stages (N0 82%, N1 78%, N2 90%, N3 93%). No statistically
      significant differences could be found between both CT methods. CONCLUSION: In
      spite of the tendency of improved diagnosis of T1, N0 and N1 stages no clear
      improvement in the staging of carcinomas of the oral cavity, the oropharynx and
      hypopharynx could be expected by spiral CT.

PMID- 10955295
TI  - [The pharynx following tumor-surgery interventions. The variability of the
      clinical images in conventional fluoroscopic diagnosis].
AB  - The present study gives a survey of radiological findings after surgical
      treatment of laryngeal and pharyngeal carcinomas, whereby the surgical procedures
      and the localisation of tumours found special consideration. One important point
      of view of modern surgery is the improvement of quality of life. By reason of
      this point the role of reconstructive surgery will become increasingly important.
      Representative radiographs between 1997 and 1999 are discussed to show the
      difficulties to distinguish between normal and pathological postoperative
      findings after operations of hypopharyngeal diverticula, after partial and total
      laryngectomy as well as after different methods of surgical reconstructions of
      pharynx. The examinations which are shown were realized with the conventional
      radioscopy. Hereby the normal radiological findings and their comparison to the
      particular postoperative specials rank first. Furthermore the early and late
      postoperative complications are mentioned. A variety of surgical procedures in
      treatment of laryngeal and pharyngeal carcinoma make new demands on the
      postoperative diagnostic possibilities especially on the postoperative
      pharyngography. The variability of the postoperative radiographs complicates the
      differentiation between normal and pathological radiological findings and only
      the exact knowledge of the performed surgical procedure allows their
      differentiation.

PMID- 10955296
TI  - [Case report: the spontaneous course of a giant myelolipoma].
AB  - Adrenal myelolipomas are rare benign, non functioning tumors, mostly small and
      asymptomatic. We report the natural history of a giant adrenal myelolipoma. We
      could follow with CT the natural progression of the tumor during a 5-year
      interval.

PMID- 10955297
TI  - [Clustered microcalcification in mammography?].

PMID- 10955298
TI  - [Kidney diseases in childhood. 2. Congenital anomalies, cystic kidney diseases,
      tumors and trauma].

PMID- 10955299
TI  - [c-fos Gene expression during emotional stress in rats: blocking by delta sleep
      inducing peptide].
AB  - An emotional stress induces an obvious immediate early gene c-fos expression in
      the brain limbic structures in the rats predisposed to emotional stress.
      Administration of the delta-sleep-inducing peptide (DSIP) was shown to inhibit
      the c-fos expression. It led to an obvious inhibition of the c-fos expression in
      paraventricular nuclei of the hypothalamus, medial and lateral parts of the
      septum of rats predisposed to emotional stress. This mechanism seems to play an
      important role in the DSIP anti-stress effects.

PMID- 10955301
TI  - [Changes in the neuronal activity in the dorsolateral pontine region caused by
      electrical stimulation of the brainstem regions inhibiting movement and the
      muscle tone].
AB  - Activity of 44 mesencephalic locomotor area's (MLR) units and 38 pontine
      inhibitory area's (PIA) units was recorded during stimulation of the giganto
      cellular reticular nucleus and oral pontine reticular nucleus inducing the
      hindlimb muscle tone inhibition in decerebrated rats. The muscle tone suppression
      was always accompanied by a decrease in the MLR and an increase in the PIA unit
      discharges. Stimulation of the brainstem inhibitory area seems to activate
      reticulospinal inhibitory system and suppress some MLR units relating to
      locomotion and muscle tone.

PMID- 10955300
TI  - [Glutamate receptor antagonists attenuate experimental catalepsy in rats].
AB  - A long-term akinesia induced by haloperidol used as an experimental model of
      catalepsy helped to reveal that a dicationic derivatives adamantane (IEM-1754)
      and phenylcyclohexyl (IEM-1925) exerted different degrees of inhibition of the
      haloperidol effect: the IEM-1754 proved to be not inferior to the most effective
      NMDA antagonist MK-801. A relatively low potency of the IEM-1925 may be due to
      its obvious equal effects both on the NMDA and the AMPA receptor channels. A good
      correlation between the anticataleptic effects of the glutamate antagonists and
      the NMDA receptor blocking activity, were found. The AMPA receptor blockade might
      negatively affect the anticataleptic potency of the drugs under study.

PMID- 10955302
TI  - [Ontogenetic formation of the ability for endogenous account of time and its
      dependence upon the anxiety level in rats].
AB  - Rats' ability for endogenous account of short time intervals progresses along
      with maturation. In 3- and 6-month old animals, it parabolically depends upon the
      level of anxiety: there is an average optimum level of anxiety needed for precise
      and effective account of time. Deviations from this level decrease the
      biochronometrical ability. In addition, a time perception dependence on
      locomotive sphere and the state of sympathetic adrenal system's peripheral part,
      was revealed.

PMID- 10955303
TI  - [Sensitivity of the cat lateral geniculate body neurons to orientation of the
      brightness gradient vector].
AB  - A new property of visual neurons: their sensitivity to orientation and the vector
      brightness gradient, was revealed and described. Receptive fields of the lateral
      geniculate body neurons in the cat have preferred orientation maximum reaction
      (average mean of orientation sensitivity coefficient--0.55 +/- 0.20). The
      preferred orientation mainly has a radial or tangential trend in the visual
      field. Temporal characteristics of the neuronal responses were analysed. A role
      of inhibition processes in the orientation sensitivity is discussed.

PMID- 10955304
TI  - [Genetic aspects of arterial hypertension: the role of Y chromosome and
      mitochondrial DNA].
AB  - A study on hybrids from reciprocal crossing of the SHR-SP and the WKY has shown
      that Y-chromosome and mitochondrial DNA the affect development of the spontaneous
      hypertension. The Y-chromosome takes part in disorders of baroreceptive
      sensitivity in phenylnephrine assay associated with hypertension. Although our
      findings suggest that structural remodelling of peripheral vascular resistance
      and an increase in noradrenaline-dependent vasocostriction is genetically
      determined in hypertensive rats, we could not corroborate the role of the Y
      chromosome and mitochondrial DNA in the process. A difference was shown between
      male and female SHR-SP in the level of arterial pressure and in development of
      the vascular structure changes.

PMID- 10955305
TI  - [Effect of localization of the ectopic excitation site on the sequence and
      duration of depolarization in the ventricular epicardium in dogs].
AB  - The depth of the myocardial wall ectopic focus was found to affect spatial and
      temporal characteristics of the depolarization process in the heart ventricular
      surface. Duration of the ventricular epicardial depolarization under the ectopic
      foci located in subendocardial and intramural layers of the myocardium was
      shorter than in epicardial stimulation of the ventricles. A dependence of the
      ectopic excitation duration on the pacing site localization in the epicardium,
      was revealed. The shortest duration of the depolarization occurred under
      electrical stimulation of the apex and ventral part of the interventricular
      septum, whereas the longer one--under pacing the left ventricular base.

PMID- 10955306
TI  - [Mechanical human heart work in a newborn infant].
AB  - The echo- and dopplerography of newborn infants up to 10-day age revealed that
      their heart work capacity was about 6 Wt, relative capacity--25 Wt/100 g of
      ventricular mass. These data correspond to those of adult humans. The Frank
      Starling mechanism was corroborated.

PMID- 10955307
TI  - [Blocking of cold paralysis of physiological functions].
AB  - For more than 100-year history of studying hypothermia a rewarming of a cooled
      organism was always considered as the only method of restoring the cold-paralysed
      physiological functions and the vital activity of an overcooled organism of
      homoiothermal animals and humans. The paper gives the results of applying the
      method developed at our Laboratory, of restoring the cold-paralysed important
      physiological functions after a continuous cooling of rats, without rewarming the
      animals.

PMID- 10955309
TI  - [Dynamics of milk ejection reflex during continuous rhythmic stimulation of
      areola-nipple complex of the mammary gland].
AB  - In continuous 10-minute simultaneous action of the vacuum and compression stimuli
      at a 1 cycle/second frequency, the rate of the milk ejection from the breast was
      periodically changing in lactating women. The milk flow first peaks latency was
      0.5-3.0 minutes, the number of peaks being 2-7 per minute with the inter-peak
      interval 2-4 minutes during a 10-minute milk ejection. The women revealed an
      individual pattern of the milk flow peaks. The findings suggest that a central
      gate mechanism intervenes to set the periodicity of the milk ejection.

PMID- 10955308
TI  - [Connections of the cat stellate ganglion with target organs during postnatal
      ontogenesis].
AB  - The enzyme horseradish peroxidase was administered into trachea, esophagus,
      heart, sternocleidomastoid muscle, and biceps of newborn, 10-, 20-day old
      kittens, and adult cats. The labeled neurons were located on the topical basis of
      the stellate ganglion. In newborn kittens, the largest cells take part in the
      heart innervation. In animals of other ages, the largest cells take part in
      innervation of the sternocleidomastoid muscle. The findings suggest that, in
      postnatal ontogenesis, neuronal organisation of the stellate ganglion is changing
      parallel to an enhancement of the neurons' size and ganglion section area.

PMID- 10955310
TI  - [The role of glucocorticoids in healing of indomethacin-induced lesions in the
      rat gastric mucosa].
AB  - Pretreatment with a single large dose of cortisol a week before indomethacin
      administration, or an adrenalectomy induced a glucocorticoid production
      deficiency in rats. The area of gastric erosions in these rats was considerably
      larger than in the control animals in 4, 24, and 48 hours after the indomethacin
      administration. Administration of corticosterone noticeably prompted the healing
      of the erosions in the rats with glucocorticoid deficiency. The findings suggest
      a gastroprotective effect of glucocorticoids in healing of indomethacin-induced
      mucosal injury.

PMID- 10955311
TI  - [The role of the peripheral nervous system in the connection of the immune system
      with the brain].

PMID- 10955312
TI  - [Assessment of the brain oxygen consumption during deep hypothermia and isolated
      perfusion of the brain with serum-free perfusate in rats].

PMID- 10955313
TI  - Language assessment of Swedish 3-year-olds using a protocol of natural speech:
      PLUS-3--productive language USe at 3.
AB  - PLUS-3 is a new Swedish protocol of natural speech in 3-year-old children. Two
      studies are reported with 27 (11 girls and 16 boys) and 12 children (4 girls and
      8 boys), respectively. The children were tape-recorded by their parents in
      dialogues based on picture books. The reliability of PLUS-3 was satisfactory
      (88%; inter-rater agreement), as was the concurrent validity measured by
      correlation with a grammar scale (rs = 0.53; p < 0.01). PLUS-3 correlated
      significantly with slightly modified mean length of utterance (MLU) measures (rs
      = 0.80; p < 0.01) and with lexical diversity (rs = 0.68; p < 0.02). In total, 30
      two-morpheme utterances were sufficient to capture the language level of a child.
      PLUS-3 was significantly associated with communicative measures collected 14
      months earlier (5 out of 8 measures, p < 0.05).

PMID- 10955315
TI  - On the differences between conventional and auditory spectrograms of English
      consonants.
AB  - A new tool for speech analysis is presented, operating in real-time and
      incorporating the analysing power of a contemporary auditory model to produce the
      familiar display of the speech spectrograph. This "auditory spectrograph" is used
      to analyse English consonant sounds and the results are compared with
      conventional wide and narrow band spectrograms. The auditory analyses are found
      to attach more visual weight to the acoustic cues associated with speech
      production and perception, and features that are either difficult or impossible
      to distinguish on conventional spectrograms are clarified.

PMID- 10955314
TI  - Perceptual and acoustic analysis of vocal registers in 10-year-old children.
AB  - Register transitions were identified by a group of five experts on child voices
      in recordings of 15 10-year-old children who sustained the vowel [a:] at
      different pitches throughout their vocal range. Two had mutational voices, seven
      had deviant voices and six were controls with normal voices. The control group
      had one register transition at a mean fundamental frequency of 511 Hz, or about
      25% higher than in adult voices. This difference between adult and child voices
      may be because of the difference in trachea length, as proposed by Titze (J.
      Voice 1988; 3: 183-194). Children with either functional or physiological voice
      deviations exhibited a transition at a mean frequency of 417 Hz. A second
      transition was found in four voices at a mean frequency of 902 Hz. No correlation
      was found between the occurrence of register transitions and discontinuities in
      the upper and lower voice range profile contours.

PMID- 10955316
TI  - Working conditions on stage: climatic considerations.
AB  - Singers and actors frequently complain about dusty and dry theater environments,
      which they believe induce respiratory tract indispositions and decrements in
      vocal performance. In the literature to date, extremely few quantitative data
      exist about actual climatic conditions on stage. A previous study by our group in
      an unhumidified theater found that it had too high temperatures, too dry and too
      dusty air, based on German occupational guidelines for the generic workplace. In
      the present study, humidification units were installed in the same theater, and
      the environmental measures were repeated. The primary findings indicated that,
      following the activation of the humidification units, temperatures, humidities
      and fine dust concentrations were improved and generally within acceptable ranges
      for the generic workplace, although not always optimal. Where unacceptable
      performance environments exist, special care should be taken to counsel
      performers with regard to possible prophylactic measures such as individual steam
      inhalation and fluid intake.

PMID- 10955317
TI  - Do we understand the speech of deaf adolescents? An evaluation and comparison of
      the intelligibility in two similar research projects from 1979 and 1995.
AB  - The intelligibility of the speech of orally educated deaf pupils was the subject
      of a research project conducted in Norway in 1979. The sample consisted of all 15
      adolescents from the 7th, 8th and 9th grades of a school that offered boarding
      accommodation. The pupils were videotaped as they uttered pre-constructed
      phrases. Normal hearing adults evaluated the speech. Some pupils were understood,
      while the speech of others was practically impossible to decipher. On average,
      about half of the words were understood. In the 1980s, teaching through sign
      language became common and articulation training became rare. To see if this
      change in teaching method reduced the intelligibility of oral speech, a
      replication study was conducted in 1995. The results of the two studies, however,
      were very similar.

PMID- 10955318
TI  - The impact of women in the practice of academic and clinical rheumatology in the
      Americas.

PMID- 10955319
TI  - Methotrexate in juvenile idiopathic arthritis: answers and questions.

PMID- 10955320
TI  - Methotrexate: more questions than answers.

PMID- 10955321
TI  - Lyme arthritis in children: is chronic arthritis a common complication?

PMID- 10955322
TI  - Complement mediated vascular endothelial injury in rheumatoid nodules: a
      histopathological and immunohistochemical study.
AB  - OBJECTIVE: To evaluate morphologically and immunohistochemically the role of IgM
      rheumatoid factor (RF) immune complexes and complement activation in rheumatoid
      nodule vascular injury, a typical extraarticular manifestation of rheumatoid
      arthritis. METHODS: Histological features such as cellular infiltration,
      endothelial alteration, fibrinoid degeneration, and basement membrane alterations
      were observed in the small vessels in rheumatoid nodules. An immunohistochemical
      study was also carried out. RESULTS: Distinct colocalization of IgM RF and
      terminal complement complexes (TCC: C5b-9) was observed on the luminal surface in
      some of the damaged endothelial cells. Immuno-electron microscopy revealed
      endothelial vesiculation, typical of the in vitro protective mechanism against
      complement attack, with deposition of not only TCC but also IgM RF. Most TCC
      positive endothelial cells simultaneously expressed the major complement
      regulatory factor, CD59. CONCLUSION: These data suggest that, in rheumatoid
      nodules, vascular injury mediated by complement activation involves the assembly
      of IgM RF on the endothelial cell surface.

PMID- 10955323
TI  - Synovitis occurs in some clinically normal and asymptomatic joints in patients
      with early arthritis.
AB  - OBJECTIVE: To determine if clinically asymptomatic knee joints in patients with
      recent onset arthritis reveal histological evidence of synovitis. METHODS: As
      part of a prospective study of patients with synovitis of less than one year
      duration, we performed blind needle biopsies on the knees of 20 patients who had
      synovitis elsewhere but no symptoms or detectable swelling or tenderness of the
      biopsied joint. RESULTS: Histologic evidence of synovitis was observed in 11
      knees (55%). All patients with synovitis had evidence of synovial lining cell
      hyperplasia, increased vascularity, and lymphocytic infiltrates. Five of 6
      patients with rheumatoid arthritis (RA) and 5 of 8 with undifferentiated
      arthritis had histological evidence of synovitis, but none of the 5 with reactive
      arthritis (ReA) had synovitis in the asymptomatic joints. Histologic evidence of
      synovitis persisted in some after clinical resolution of previous pain and
      swelling, while it occurred in others with no history of previous involvement of
      that knee. CONCLUSION: Even asymptomatic joints in patients with RA and
      undifferentiated arthritis of recent onset reveal histologic signs of synovitis.
      The earliest changes may occur before symptoms. Histologic changes also persist
      after resolution of previous early symptoms. Evidence of inflammation was not
      present in asymptomatic joints in our 5 patients diagnosed with ReA.

PMID- 10955325
TI  - Longterm methotrexate use in rheumatoid arthritis: 12 year followup of 460
      patients treated in community practice.
AB  - OBJECTIVE: To extend our observations on the longterm tolerability of
      methotrexate (MTX) and reasons for discontinuation in a cohort of 460 patients
      with rheumatoid arthritis (RA). METHODS: We studied all patients with RA who
      started MTX before June 1986 and attended the community based private practices
      of 6 rheumatologists in Melbourne. Information to at least April 1, 1995, or
      within one year of death was updated from the patient's medical records to
      include MTX discontinuation and reasons for discontinuation. Addition of disease
      modifying antirheumatic drugs (DMARD) concomitant with MTX was noted. Survival
      analyses based upon life table methods were used with MTX discontinuation as the
      observable endpoint. Three different definitions of MTX discontinuation were used
      (1) according to whether the patient was taking the drug at last followup
      irrespective of any periods of temporary discontinuation; (2) MTX discontinuation
      for > 3 months considered to be a treatment endpoint; and (3) addition of
      concomitant DMARD considered to be only partial success of MTX (as a need for
      additional therapy to meet treatment goals). RESULTS: At 12 years, 53% of
      patients were continuing to take MTX (irrespective of any periods of temporary
      discontinuation). If discontinuation of the drug for 3 or more months was
      considered a treatment termination then 38% were still taking the drug at 12
      years, and if addition of concomitant DMARD was regarded as a treatment endpoint
      only 17% of patients were continuing MTX at 12 years. Withdrawal for
      gastrointestinal toxicity declined over time but the risk of other adverse
      effects appeared to persist over time. CONCLUSION: MTX in RA is well tolerated
      over the longer term, with > 50% of patients starting MTX in a community based
      rheumatology private practice continuing to take it 12 years later. However, a
      substantial number of patients had 2nd line therapies added over this time.
      Monitoring for toxicity should continue throughout the course of therapy.

PMID- 10955324
TI  - Treatment of rheumatoid arthritis with a DR4/1 peptide.
AB  - OBJECTIVE: To determine the safety and potential clinical efficacy of primary and
      booster injections of a DR4/1 peptide in patients with active rheumatoid
      arthritis (RA) despite methotrexate therapy. METHODS. Subjects with active RA
      were enrolled in a randomized, placebo controlled, double blind, dose-escalating
      clinical trial of synthetic DR4/1 peptide containing the shared epitope. The
      primary injection of the DR4/1 peptide in alum adjuvant was administered at one
      of 3 doses, 1.3, 4.0, and 13 mg, followed by up to 3 or 4 booster injections
      every 6 or 8 weeks at the same dose. The primary outcomes were the occurrence of
      adverse effects and changes in measures of immune function. Clinical efficacy was
      assessed using the American College of Rheumatology 20% criteria for clinical
      improvement. RESULTS: Fifty-three patients were entered into the trial, including
      44 who completed the study. In the absence of any observations of a dose response
      to the DR4/1 peptide injections, the 3 dosage groups were combined for subsequent
      analysis into 3 groups: patients receiving DR4/1 peptide injections every 6
      weeks, patients receiving DR4/1 peptide injections every 8 weeks, and a placebo
      group. At all doses and each dosing interval the primary and booster injections
      of synthetic DR4/1 peptide were well tolerated and did not produce any
      significant changes in lymphocyte counts or evidence of generalized
      immunosuppression. Analysis of clinical efficacy showed that the 6 week group had
      trends toward improvement in disease measures. CONCLUSION: Primary and booster
      injections of the DR4/1 peptide containing the shared epitope were safe and did
      not broadly suppress immune function.

PMID- 10955326
TI  - Low dose weekly methotrexate in early pregnancy. A case series and review of the
      literature.
AB  - OBJECTIVE: To assess the teratogenic risk of low dose weekly pulses of
      methotrexate (MTX) inadvertently taken during the first trimester of pregnancy.
      METHODS: We assessed pregnancy and neonatal outcome of 4 patients with rheumatic
      disease treated with weekly pulses of 5 to 15 mg of MTX for a mean duration of 4
      years. RESULTS: The 4 patients had continued MTX treatment from one to 6 weeks of
      gestation. One patient miscarried at Week 6, the other pregnancies ended with the
      delivery of healthy children. Chromosome analysis of one child was normal.
      CONCLUSION: In spite of the absence of congenital anomalies in our cases, safe
      contraception in fertile patients who start low dose weekly MTX is mandatory.

PMID- 10955327
TI  - Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor,
      compared to naproxen and placebo.
AB  - OBJECTIVE: To determine the upper gastrointestinal (GI) tolerability of
      celecoxib, naproxen, and placebo in patients with rheumatoid arthritis (RA) and
      osteoarthritis (OA). METHODS: An analysis of 5, 12-week, randomized, double
      blind, parallel group, placebo controlled clinical trials was conducted. In these
      trials, patients were randomized to: naproxen 500 mg bid (n = 1,099), placebo (n
      = 1,136), celecoxib 50 mg bid (n = 690) (subtherapeutic dose), celecoxib 100 mg
      (n = 1,131) or 200 mg bid (n = 1,125) (therapeutic dose), or celecoxib 400 mg bid
      (n = 434) (supratherapeutic dosage). The incidence and time until moderate to
      severe abdominal pain, dyspepsia, nausea, and any of the aforementioned 3 upper
      GI symptoms (composite endpoint) were determined using time-to-event analysis.
      RESULTS: The cumulative incidences of moderate to severe abdominal pain,
      dyspepsia, or nausea (composite endpoint) were: naproxen 500 mg (12.0%; 95% CI
      9.9%-14.0%), celecoxib 50 mg bid (7.1%; 95% CI 5.0%-9.2%), celecoxib 100 mg bid
      (7.8%; 95% CI 6.0%-9.5%), celecoxib 200 mg bid (8.1%; 95% CI 6.4%-9.9%),
      celecoxib 400 mg bid (6.0%; 95% CI 3.6%-8.4%), and placebo (8.5%; 95% CI 6.5%
      10.8%). After controlling for independent predictors of the composite endpoint,
      relative risks (RR) for the various treatments relative to naproxen 500 mg bid
      were: celecoxib 50 mg (RR 0.54; 95% CI 0.37-0.77; p < 0.001), celecoxib 100 mg
      (RR 0.60; 95% CI 0.45-0.80; p < 0.001), celecoxib 200 mg bid (RR 0.63; 95% CI
      0.47-0.83; p = 0.001), celecoxib 400 mg bid (RR 0.56; 95% CI 0.35-0.89; p =
      0.015), and placebo (RR 0.63; 95% CI 0.47-0.85; p = 0.002). After controlling for
      independent predictors of the composite endpoint, celecoxib treatment group
      patients did not differ from placebo patients when reporting the composite
      endpoint, with p values ranging from 0.40 to 0.96. CONCLUSION: The upper GI
      tolerability of celecoxib is superior to naproxen. A dose-response relationship
      between celecoxib and upper GI symptoms was not apparent.

PMID- 10955328
TI  - Systemic lupus erythematosus in North American Indians: a population based study.
AB  - OBJECTIVE: To evaluate the prevalence, disease course, and survival of patients
      with systemic lupus erythematosus (SLE) in a population of over 120,000 North
      American Indians (NAI), and contrast the results to those in the non-Indian
      population. METHODS: The regional arthritis center database and the medical
      records of all rheumatologists, hematologists, nephrologists, and general
      internists with > 1 patient with SLE were searched for cases of SLE diagnosed
      between 1980 and 1996. A random survey of 20% of family physicians serving this
      population suggested that > 85% of all SLE cases were identified. Demographics,
      SLE Disease Activity Index (SLEDAI) scores, Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage scores.
      clinical manifestations, and therapy for NAI were contrasted with the results in
      Caucasians (CAUC). RESULTS: We identified 257 cases meeting the ACR criteria for
      SLE diagnosed between 1980 and 1996. There were 49 NAI cases, resulting in a
      prevalence of 42.3/100,000, compared to a prevalence of 20.6/100,000 for the
      remainder of the population. NAI patients were younger at diagnosis, had higher
      SLEDAI scores at diagnosis, and had more frequent vasculitis, proteinuria and
      cellular casts. There were no treatment differences at diagnosis or at 2 years,
      but NAI patients were significantly more likely to receive treatment with
      prednisone or immunosuppressives at the last clinic visit. The NAI patients had
      similar damage scores at diagnosis, but significantly higher scores at 2 years
      and at the last clinic visit. NAI ethnicity increased the likelihood of death
      more than 4-fold. CONCLUSION: The prevalence of SLE was increased 2-fold in the
      NAI population. NAI patients had higher SLEDAI scores at diagnosis and more
      frequent vasculitis and renal involvement, required more treatment later in the
      disease course, accumulated more damage following diagnosis, and had increased
      fatality.

PMID- 10955329
TI  - Prediction of short term mortality in systemic lupus erythematosus with time
      dependent measures of disease activity.
AB  - OBJECTIVE: To identify predictors of short term mortality in systemic lupus
      erythematosus (SLE) in terms of time dependent clinical indicators of disease
      activity from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).
      METHODS: We studied data collected on patients followed at the University of
      Toronto Lupus Clinic. Clinical and laboratory indicators of disease activity are
      recorded at each clinic visit and a SLEDAI summary score is calculated. Survival
      analyses were conducted in which the prognostic value of the time dependent
      indicators of disease activity was examined on 6-month mortality through a
      multivariate Cox regression model. Relative risks, confidence intervals, and
      significance levels were obtained for each indicator to reflect their clinical
      importance and statistical significance. RESULTS: The sample consisted of 806
      patients followed for a median of 6.6 years; 702 (87%) were female, 671 (83%)
      were Caucasian, and the mean age at first clinic visit was 36 years. Seventy-two
      patients died within 6 months of their last clinic visit. In a univariate
      regression model, a categorical variable reflecting total SLEDAI score was highly
      prognostic for mortality (p < 0.001) and yielded increasing relative risks of
      1.28 for SLEDAI 1-5 vs 0, 2.34 for SLEDAI 6-10 vs 0, 4.74 for SLEDAI 11-19 vs 0,
      and 14.11 for SLEDAI > 20 vs 0. In a separate multivariate Cox model examining
      the individual components of SLEDAI, presence of organic brain syndrome, retinal
      changes, cranial nerve involvement, proteinuria, pyuria, pleurisy, fever,
      thrombocytopenia, and leukopenia each significantly increased the risk of death,
      while new rash and anti-DNA antibodies conferred protective effects. CONCLUSION:
      This time dependent Cox regression analysis identified the extent to which SLE
      disease activity, revealed by SLEDAI, is prognostic for short term mortality.
      Further, important individual components were identified and their prognostic
      value for death was estimated.

PMID- 10955330
TI  - Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjogren's
      syndrome-like autoimmune exocrinopathy.
AB  - OBJECTIVE: NOD mice exhibit at least 2 overlapping autoimmune diseases:
      autoimmune endocrinopathy (Type I, insulin dependent diabetes) and autoimmune
      exocrinopathy (Sjogren's syndrome, SS). To date, 18 chromosomal regions have been
      identified that contribute to development of diabetes in NOD mice; however,
      genetic mapping of similar susceptibility loci for autoimmune exocrinopathy is
      just beginning. We investigated if these 2 autoimmune diseases share a genetic
      predisposition. METHODS: Congenic partner strains of NOD and C57BL/6 mice
      containing defined genetic intervals influencing susceptibility to diabetes (Idd)
      were screened for histological and biochemical markers for their effect on the
      development of SS-like disease. Saliva flow rates, protein concentration, amylase
      activity, and cysteine protease activity were evaluated. RESULTS: In contrast to
      the nonsusceptible parental C57BL/6 strain, C57BL/6.NOD Idd5 congenic partner
      strain, containing a genetic region derived from chromosome 1 of the NOD mouse,
      exhibited pathophysiological characteristics of autoimmune exocrinopathy.
      Replacement of individual diabetes susceptibility intervals Idd3, Idd5, Idd13,
      Idd1, and Idd9, as well as a combination of the Idd3, Idd10, and Idd17 intervals,
      with resistance alleles had little effect on development of autoimmune
      exocrinopathy. Conversely, NOD mice, in which the chromosome regions containing
      both Idd5 and Idd3 have been replaced by intervals derived from C57BL mice,
      exhibit a reduced pathophysiology associated with SS-like autoimmune
      exocrinopathy. CONCLUSION: Alleles on chromosomes 1 (Idd5) and 3 (Idd3) in
      combination appear to greatly influence susceptibility and resistance to
      development of autoimmune exocrinopathy. The association with certain Idd, but
      not other Idd loci, indicate that genetic overlap is present but probably not
      inclusive.

PMID- 10955331
TI  - Clinical course of primary Sjogren's syndrome: salivary, oral, and serologic
      aspects.
AB  - OBJECTIVE: To assess changes in symptoms and signs, salivary function, serologic
      activity, and disease progression in primary Sjogren's syndrome (SS). METHODS:
      Treatment records on 80 patients seen in clinic and diagnosed with primary SS by
      defined criteria were reviewed. Forty-nine patients were evaluated at least twice
      a minimum of 5 years (mean 7 years) apart. Salivary flow rates from each of the
      major salivary glands and laboratory values were obtained. A structured interview
      with questions pertaining to signs and symptoms of primary SS was given and a
      physical examination was performed. An additional 26 patients completed a
      followup questionnaire by mail and their current medical records were obtained
      for review. For this group, the followup period was a mean of 10 years after
      their initial evaluation. Five patients were deceased. RESULTS: The patients seen
      twice showed relative stability in their salivary measurements and in their
      serologic values. The subjective sicca symptoms of oral and ocular dryness among
      the 75 surviving patients remained prominent. Very few individuals developed
      another connective tissue disease, therefore evolving into secondary SS. Among
      the 80 patients, 6 cases of B cell lymphoma were recognized during the followup
      period. CONCLUSION: Although it is not a benign condition, primary SS is a very
      slowly progressing disease without rapid deterioration in salivary function,
      systemic markers of disease activity, or dramatic changes in symptoms, with the
      exception of a high incidence of lymphoma.

PMID- 10955332
TI  - Labeled neoglycoproteins and human lectins as diagnostic and potential functional
      markers in salivary glands of patients with Sjogren's syndrome.
AB  - OBJECTIVE: The profile of glycans and their recognition by endogenous receptors
      (lectins) are increasingly attributed to disease process. Monitoring this can
      provide information on the pathogenesis of Sjogren's syndrome (SS). Commonly,
      plant lectins are employed for phenomenological glycan mapping. To go beyond this
      approach restricted to binding of exogenous probes, new markers measure ligand
      properties of glycans to human (not plant) lectins and the presence of sugar
      receptors completing a protein-carbohydrate recognition system. Carrier
      immobilized sugar epitopes (neoglycoproteins) and purified human lectins
      establish this innovative panel. METHODS: The host defence molecules mannan
      binding lectin, serum amyloid P component, and the macrophage migration
      inhibitory factor-binding sarcolectin, selected for their involvement in cell
      destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA
      were employed to monitor regulation of potential ligand sites for I-type lectins
      and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The
      specific binding characteristics were determined by quantitative morphometry and
      statistical analysis. RESULTS: Diagnostic information emerged from this analysis.
      The percentage of stained tissue area was significantly different between SS and
      control specimens after processing with GlcNAc and Man-bearing neoglycoproteins
      and the 2 tested serum lectins. For separation of cases of primary and secondary
      SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the
      exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically
      significant. CONCLUSION: Saccharide-presenting probes to measure the cellular
      capacity to bind glycan epitopes and human lectins as sensors for endogenous
      binding sites have proven to be useful as diagnostic tools. We suggest the
      differences we observed reflect aberrations from the normal cellular homeostasis
      with relevance for the pathogenesis of SS and its manifestation as a primary or
      secondary syndrome.

PMID- 10955333
TI  - Serum levels of soluble interleukin 6 receptor and soluble gp130 are elevated in
      patients with localized scleroderma.
AB  - OBJECTIVE: To investigate the clinical relevance of serum soluble interleukin 6
      receptor (sIL-6R) and soluble gp130 (sgp130) in localized scleroderma. METHODS:
      Serum levels of sIL-6R and sgp130 were examined by ELISA in 45 patients with
      localized scleroderma. Twenty patients with systemic sclerosis (SSc) and 20
      healthy individuals served as controls. RESULTS: Serum levels of both sIL-6R and
      sgp130 were significantly elevated in patients with localized scleroderma
      compared with healthy controls. Moreover, serum sgp130 levels in patients with
      localized scleroderma were significantly higher than in patients with SSc. In
      patients with localized scleroderma, elevated sIL-6R levels significantly
      correlated with levels of IgM antihistone antibodies, the presence of rheumatoid
      factor, the number of linear lesions, and the number of body areas involved.
      Elevated sgp130 levels were significantly associated with levels of IgG
      antihistone antibodies, the number of plaque lesions, the total number of
      lesions, and the number of body areas involved. CONCLUSION: These results suggest
      that elevated serum sIL-6R and sgp 30 may reflect activation of the IL-6 system
      that may be associated with the development of sclerotic lesions and autoantibody
      production in localized scleroderma.

PMID- 10955334
TI  - Longterm therapy of psoriatic arthritis: intramuscular gold or methotrexate?
AB  - OBJECTIVE: To compare the efficacy and toxicity of methotrexate (MTX) and
      intramuscular (im) gold in the treatment of psoriatic arthritis (PsA). METHODS:
      Medical records from all patients with PsA attending the gold and MTX clinics at
      the Vancouver Mary Pack Arthritis Centre between 1971 and 1995 were reviewed. The
      odds of a clinical response (defined as at least a 50% reduction in active joint
      count from initial to last visit or for at least 6 months) and the relative risk
      of discontinuing therapy associated with treatment (MTX or im gold) were
      calculated after controlling for significant baseline covariates, using logistic
      regression and Cox regression analyses, respectively. The frequency of side
      effects and the reasons for treatment cessation were also compared between
      treatment groups. RESULTS: Eighty-seven patients received 111 treatment courses:
      43 of MTX and 68 of im gold. The likelihood of a clinical response was 8.9 times
      greater (95% CI 1.8; 44.0) with MTX than im gold. Patients were 5 times more
      likely (95% CI 2.4; 10.4) to discontinue therapy with im gold than with MTX. No
      major toxicity occurred and frequency of side effects was similar for both
      treatments. Patients with a longer duration of PsA prior to initiation of study
      treatment were less likely to achieve a clinical response. CONCLUSION: MTX and im
      gold are safe and well tolerated in the treatment of PsA. In our experience. MTX
      was superior to im gold in the likelihood of achieving a clinical response and in
      permitting an individual to continue longterm treatment. Our data suggest that
      earlier treatment may be associated with a better response.

PMID- 10955335
TI  - A comparison study of the back pain functional scale and Roland Morris
      Questionnaire. North American Orthopaedic Rehabilitation Research Network.
AB  - OBJECTIVE: To determine whether the measurement properties of the Back Pain
      Functional Scale (BPFS) are superior to the Roland-Morris Questionnaire (RMQ).
      METHODS: The BPFS and RMQ were administered on multiple occasions to 153 patients
      with low back pain attending physical therapy. Eleven Canadian clinics and 8
      American clinics participated in the study. Ceiling effects, internal
      consistency, test-retest reliability, cross sectional discriminant validity, and
      sensitivity to change were investigated. Error estimates in scale points were
      obtained. RESULTS: A ceiling effect was noted for 6 patients' RMQ scores compared
      to 3 patients' BPFS scores. Internal consistency for the RMQ and BPFS were 0.87
      and 0.93, respectively. The error (95% CI) for a patient's score was +/- 15.5% of
      the scale range for the RMQ and +/- 10.5% for the BPFS. The test-retest
      reliability was 0.79 for the RMQ and 0.82 for the BPFS. The error associated with
      a patient's change score (95% CI) was 27.7% of the scale range for the RMQ and
      22.2% for the BPFS. The measures showed similar levels of discriminant validity
      with respect to physical findings, work status, and education level. The BPFS was
      more adept at detecting different amounts of change in patients with back pain of
      less than 2 weeks' duration compared to patients with back pain of 2 or more
      weeks' duration. CONCLUSION: The BPFS is a competitive functional status measure
      for patients with low back pain.

PMID- 10955336
TI  - A comparison of lower extremity muscle strength, obesity, and depression scores
      in elderly subjects with knee pain with and without radiographic evidence of knee
      osteoarthritis.
AB  - OBJECTIVE: To determine, in subjects with knee pain but no radiographic changes
      of tibiofemoral or patellofemoral compartment osteoarthritis (OA), whether mean
      body weight, quadriceps and hamstring strength, lower extremity muscle mass,
      depression scores, and perceptions of their general health status differed from
      those of subjects with symptomatic knee OA. METHODS: Subjects were 25 women and
      10 men with knee pain and radiographic evidence of OA at the baseline
      examination, and 21 women and 16 men who had knee pain at the baseline
      examination but no radiographic evidence of knee OA at either baseline
      examination or followup evaluation performed, on average, 31 months later. These
      individuals were a subset of a cohort of 462 independently living elderly
      individuals recruited by telephone interview after random selection through
      random digit dialing of households in central Indiana. Data from an additional
      134 subjects who had neither knee pain nor radiographic changes of OA at either
      the baseline or followup examination were analyzed for comparison. Lower
      extremity muscle strength was measured by isokinetic dynamometry, lean tissue
      (i.e., muscle) mass in the lower extremities by dual x-ray absorptiometry,
      depression by Center for Epidemiology Depression (CES-D) scale. knee pain by
      Western Ontario McMaster University OA instrument, and perceived general health
      status by the Medical Outcome Survey Short Form-36. RESULTS: In contrast to those
      with symptomatic knee OA, those who had knee pain but no radiographic evidence of
      OA were less obese, had hamstring as well as quadriceps weakness, and had CES-D
      scores high enough to qualify for a diagnosis of clinical depression. CONCLUSION:
      Among subjects with knee pain but no OA--and among women in this subset, in
      particular--knee pain may be a manifestation of depression. rather than of joint
      disease.

PMID- 10955337
TI  - The effects of a health educational and exercise program for older adults with
      osteoarthritis for the hip or knee.
AB  - OBJECTIVE: Evaluation of a self-management program for patients with
      osteoarthritis (OA) of the hip or knee. The program, which consisted of 6 weekly
      sessions of 2 hours, included health education by a peer and physical exercises
      taught by a physical therapist. METHODS: Randomized controlled trial. Inclusion
      criteria were diagnosis of OA of the hip or knee according to ACR clinical and
      radiographic criteria and age 55 to 75 years. EXCLUSION CRITERIA: on waiting list
      for joint replacement. There were pretest, posttest, and followup (6 months)
      assessments. The experimental group consisted of 56 patients, the control group
      49. Outcome variables were pain, quality of life, activity restrictions,
      knowledge about OA, self-efficacy, body mass index (BMI), and mobility measures.
      Attention was also paid to effects on health care utilization and lifestyle
      behavior. RESULTS: Significant MANOVA group x time effects (p < 0.05, one-sided)
      were found for pain, quality of life, strength of the left M. quadriceps,
      knowledge, self-efficacy, BMI, physically active lifestyle, and visits to the
      physical therapist. Most effects were moderate at posttest assessment and smaller
      at followup. No effects were found for range of motion and functional tasks.
      CONCLUSION: The program was reasonably effective, but more attention should be
      paid to proactive followup interventions and to the selection of participants.

PMID- 10955338
TI  - Acetabular labrum in hip dysplasia evaluated by radial magnetic resonance
      imaging.
AB  - OBJECTIVE: To numerically express morphologic conditions and signal intensity in
      the acetabular labrum of the weight-bearing portion of hip joints in patients
      with hip dysplasia. METHODS: Using a radial magnetic resonance imaging (MRI)
      technique, where the planes are set radially centered on the midpoint of
      acetabulum, and which depicts the entire acetabular rim and acetabular labrum, we
      investigated 60 hip joints of 35 patients with hip dysplasia. RESULTS: The
      acetabular labrum was larger in dysplastic hips than in normal hips, and the size
      increased in the posterosuperior portion. All patients had portions with signal
      intensity changes within the labrum and had impairment on the labrum. When
      osteoarthrosis due to hip dysplasia was observed, signal intensity changes
      increased. The changes of intensity varied among the portions observed, and were
      stronger in the anterosuperior portions than in the superior and posterosuperior
      portions. CONCLUSION: Radial MRI numerically depicts morphologic conditions of
      acetabular labrum; the data were usable to evaluate the size difference in
      acetabular labrum due to hip dysplasia and the degree of impairment.

PMID- 10955339
TI  - Low level laser therapy for osteoarthritis and rheumatoid arthritis: a
      metaanalysis.
AB  - OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) affect a large
      proportion of the population. Low level laser therapy (LLLT) was introduced as an
      alternative noninvasive treatment for RA and OA about 10 years ago, but its
      effectiveness is still controversial. We assessed the effectiveness of LLLT in
      the treatment of RA and OA. METHODS: A systematic review was conducted, following
      an a priori protocol, according to the methods recommended by the Cochrane
      Collaboration. Trials were identified by a literature search of Medline, Embase,
      and the Cochrane Controlled Trials Register. Only randomized controlled trials of
      LLLT for the treatment of patients with a clinical diagnosis of RA or OA were
      eligible. Thirteen trials were included, with 212 patients randomized to laser
      and 174 patients to placebo laser, and 68 patients received active laser on one
      hand and placebo on the opposite hand. Treatment duration ranged from 4 to 10
      weeks. Followup was reported by only 2 trials for up to 3 months. RESULTS: In
      patients with RA, relative to a separate control group, LLLT reduced pain by 70%
      relative to placebo and reduced morning stiffness by 27.5 min (95% CI -52.0 to 
      2.9), and increased tip to palm flexibility by 1.3 cm (95% CI -1.7 to -0.8).
      Other outcomes such as functional assessment, range of motion, and local swelling
      were not different between groups. There were no significant differences between
      subgroups based on LLLT dosage, wavelength, site of application, or treatment
      length. In RA, relative to a control group using the opposite hand, there was no
      difference between control and treatment hand, but all hands were improved in
      terms of pain relief and disease activity. For OA, a total of 197 patients were
      randomized. Pain was assessed by 3 trials. The pooled estimate (random effects)
      showed no effect on pain (standardized mean difference -0.2, 95% CI -1.0 to
      +0.6), but there was statistically significant heterogeneity (p > 0.05). Other
      outcomes of joint tenderness, joint mobility, and strength were not significant.
      CONCLUSION: LLLT should be considered for short term relief of pain and morning
      stiffness in RA, particularly since it has few side effects. For OA, the results
      are conflicting in different studies and may depend on the method of application
      and other features of the LLLT. Clinicians and researchers should consistently
      report the characteristics of the LLLT device and the application techniques. New
      trials on LLLT should make use of standardized, validated outcomes. Despite some
      positive findings, this metaanalysis lacked data on how effectiveness of LLLT is
      affected by 4 factors: wavelength, treatment duration of LLLT, dosage, and site
      of application over nerves instead of joints. There is a need to investigate the
      effects of these factors on effectiveness of LLLT for RA and OA in randomized
      controlled clinical trials.

PMID- 10955340
TI  - The relative importance of cysteine peptidases in osteoarthritis.
AB  - OBJECTIVE: To assess the activity of cysteine peptidases in cultured human
      articular chondrocytes as well as in osteoarthritic (OA) cartilage and
      subchondral bone, and to interpret their relative importance in cartilage
      destruction and remodeling of the subchondral region. METHODS: Intracellular and
      secreted cysteine peptidase activity was measured in chondrocytes using
      fluorimetric assays, and enzymes were immunolocalized using monospecific
      antibodies. Enzyme histochemistry in normal and OA femoral heads was used to
      characterize enzymatic activity in full thickness samples containing cartilage
      and subchondral bone. The zonal distribution of cathepsin activity was measured
      in tissue slices of normal and OA femoral heads cut parallel to the joint
      surface, using fluorogenic substrates. RESULTS: Cathepsins B and L were localized
      by immunohistochemistry with lysosome-like structures in dedifferentiated
      chondrocytes. Free cysteine peptidase activity (i.e., not requiring prior
      activation), secreted and intracellularly stored by chondrocytes, was due to
      cathepsin B, while cathepsin L contributed a minor fraction of the total
      activity, and was seen only after activation at acidic pH. Histochemistry and
      activity measurements confirmed cathepsin B as the major, active cysteine
      peptidase in OA cartilage, particularly at sites where matrix neosynthesis took
      place. However, free cathepsin L and/or cathepsin K activity was found
      subchondrally in association with cathepsin B in osteophytes, in zones undergoing
      bone remodeling, and at sites of inflammation. CONCLUSION: Cathepsin B, not
      cathepsin L or cathepsin K, is a candidate for articular cartilage catabolism in
      OA. While cathepsin K is the major osteoclastic cysteine peptidase, cathepsin L
      and cathepsin B may also participate in the remodeling processes of bone as well
      as in bone erosion by inflammatory cells.

PMID- 10955341
TI  - Intramuscular clodronate in nonresponders to oral alendronate therapy for
      osteoporosis.
AB  - OBJECTIVE: Oral alendronate is effective in increasing bone mineral density (BMD)
      and in reducing fracture incidence. However, a large proportion of patients under
      treatment do not show significant changes in BMD, or even bone loss. Incorrect
      administration, low intestinal absorption, and poor compliance are among factors
      that may account for this effect. In this subgroup of patients we evaluated
      whether intramuscular (im) clodronate increased the number of responders.
      METHODS: Using an open case-control design we studied 60 postmenopausal
      osteoporotic women (mean age 58.9 years +/- 4.8 SD) after one year of therapy
      with oral alendronate who had an increase in BMD that was lower than the in vivo
      densitometry measurement error (2%). Subjects were divided into 2 groups: the
      first continued aledronate treatment (AL group); the second began weekly im
      injections of clodronate 100 mg (CL group). BMD measurements were performed at
      the right femoral neck by the same operator, using dual energy x-ray
      absorptiometry. RESULTS: After 12 months of therapy the prevalence of responders
      (increase in BMD > 2%) was 40% in the AL group and 66% in the CL group
      (prevalence rate ratio = 1.65; 95% CI 1.25-2.04). The treatment group was the
      only variable that showed a significant correlation with being a responder (beta
      = 1.13; p = 0.03), as analyzed by multiple logistic regression to account for the
      effect of confounding factors. In the CL group the difference in the mean value
      of BMD between time T0 and time T+12 was greater than in the AL group, but did
      not reach statistical significance. The mean percentage variation of BMD was
      significantly greater in the CL group (+3.21%) compared to the AL group (+0.98%)
      (p < 0.001, t test) (f value = 8.4; p < 0.01, by multiple linear regression
      analysis using the same covariates). CONCLUSION: Treatment with weekly
      intramuscular injection of clodronate in nonresponders to oral alendronate showed
      a higher number of subjects with a significant increase in BMD, compared to
      continuation of therapy with alendronate.

PMID- 10955342
TI  - Validation of a German version of the Fibromyalgia Impact Questionnaire (FIQ-G).
AB  - OBJECTIVE: To translate the Fibromyalgia Impact Questionnaire (FIQ) into German
      and to evaluate its reliability and validity for the use of German speaking
      patients with fibromyalgia (FM). METHODS: We administered the FIQ to 55 patients
      with FM (15 patients filled out the questionnaire 10 days later) together with
      German versions of the Stanford Health Assessment Questionnaire (HAQ), the
      Medical Outcomes Survey Short Form-36 (SF-36), and a tender point count (TPC).
      All patients were asked about the severity of pain today (10 cm visual analog
      scale) and the duration of symptoms. Tenderness thresholds were assessed by
      dolorimetry at all tender points with a Fisher dolorimeter and laboratory tests
      were obtained. Test-retest reliability was assessed using Spearman correlations.
      Internal consistency was evaluated with Cronbach's alpha of reliability.
      Construct validity of the FIQ was evaluated by correlating the HAQ and subscales
      of the SF-36 as well as the TPC and the tenderness thresholds. RESULTS: Mean age
      of participants was 54.3 years and mean duration of symptoms 9.5 years. Test
      retest reliability was between 0.62 and 1 for the physical functioning as well as
      for the total FIQ and other components. Internal consistency was 0.92 for the
      overall FIQ. Significant correlations were obtained between the FIQ items, the
      HAQ, and the SF-36. CONCLUSION: The German FIQ is a reliable and valid instrument
      for measuring functional disability and health status in German patients with FM.

PMID- 10955343
TI  - The assessment of functional impairment in fibromyalgia (FM): Rasch analyses of 5
      functional scales and the development of the FM Health Assessment Questionnaire.
AB  - OBJECTIVE: Functional assessment by self-report questionnaire plays an important
      role in most rheumatic conditions, but psychometric properties of questionnaires
      have not been studied in fibromyalgia (FM), particularly by Rasch analysis, which
      allows for examining adequacy of the questionnaire scale. To assess currently
      used instruments, we examined the Fibromyalgia Impact Scale (FIQ), 4 versions of
      the Health Assessment Questionnaire (HAQ), and the Medical Outcome Survey Short
      Form (SF-36). METHODS: More than 2,500 patients from 4 sites (3 US, 1 Israel)
      completed the FIQ. The HAQ questionnaires were completed by 1438 patients
      participating in the US National Data Bank for Rheumatic Diseases. Seven hundred
      sixty patients from Wichita, Kansas, completed the SF-36. Rasch analysis was
      applied separately to each of these data sets. RESULTS: The FIQ systematically
      underestimated functional impairment by its handling of activities not usually
      performed. All questionnaires had problems with non-unidimensionality and
      ambiguous items when applied to patients with FM. In addition, scales were found
      to be non-linear. Because of these findings we used the 20 item HAQ questionnaire
      as an item bank to develop a new questionnaire more suitable for use in FM, the
      fibromyalgia HAQ (FHAQ). This questionnaire fits the Rasch model well, is
      relevant, is linear, and has a long, well spaced scale. CONCLUSION: No available
      functional assessment questionnaire works well in FM. A new questionnaire, the
      FHAQ, was developed. It has appropriate metric properties and should function
      well in this condition. Since the FHAQ is a subset of the larger HAQ
      questionnaire, a new questionnaire is not required; only a different method of
      scoring is needed. Additional studies regarding sensitivity to change are
      required to fully validate the FHAQ.

PMID- 10955344
TI  - Measuring the epidemiology of distress: the rheumatology distress index.
AB  - OBJECTIVES: (1) To examine clinical and psychological variables to determine
      which are associated with psychologic and psychosocial severity or "distress";
      (2) to investigate whether patients with the 2 major rheumatic disorders,
      rheumatoid arthritis (RA) and osteoarthritis (OA), differ in distress variables
      and distress; and (3) to develop and validate a simple, clinically acceptable
      index of distress suitable for routine care and research purposes. METHODS: A
      total of 2,403 patients were evaluated in 2 data sets (N = 1,399 and N = 1,490).
      The first data set was evaluated in the clinic by a routine clinical examination
      and administration of the Clinical Health Assessment Questionnaire (CLINHAQ).
      This instrument includes measures of pain, global severity, functional
      disability, anxiety, depression, sleep disturbance, fatigue, health satisfaction,
      and health status. The second data set was evaluated by a mailed questionnaire
      that included the CLINHAQ, but also coping scales, the Beliefs in Pain Control
      Questionnaire, the Self Performance Scale, and the Arthritis Helplessness Index.
      RESULTS: RA and OA groups had similar scores for the variables associated with
      distress: pain, global severity, functional disability, anxiety, depression,
      sleep disturbance, fatigue, health satisfaction, and health status. Patients with
      fibromyalgia (FM) had more abnormal scores for every variable, reflecting overall
      distress. Using patients with FM as a "gold standard" of distress, we developed
      an index in data set 2. the Rheumatology Distress Index (RDI), made up of 5
      variables, anxiety, depression, global severity, fatigue, and sleep disturbance,
      that best identified patients with FM compared to other patients. We then
      validated the instrument on the distress severity clusters formed in data set 1.
      The correlation between RDI and distress severity cluster was 0.874 with all
      patients considered and 0.867 with FM patients excluded. In addition, RDI
      predicted 1,174 of 1,399 (83.9%) cluster memberships correctly. Compared with a
      battery of psychological and clinical tests that classified 74% of FM and non-FM
      patients correctly, the RDI and is only slightly less effective, classifying
      70.3% correctly. CONCLUSION: Distress is a patient rather than a disease
      phenomenon. A simple, easy to administer self-report questionnaire can be used to
      classify patients according to their level of distress. The resulting index, the
      RDI. accurately identifies distressed and non-distressed patients. Such an index
      should be useful for patient care and research.

PMID- 10955345
TI  - Does being a woman make a difference in professional practice? A qualitative view
      to the practice of rheumatology.
AB  - OBJECTIVE: To explore to what extent female rheumatologists perceived that gender
      had an influence on their professional practice or on their choice of specialty.
      METHODS: We collected data from 29 female rheumatologists and used qualitative
      and quantitative methods to describe the findings. RESULTS: Three groups of
      respondents were identified (cluster analysis). Most of these rheumatologists
      perceived that gender influenced the way they practiced, although the specific
      weights of the topics were different in the 3 groups. Gender also influenced
      these physicians' choice of specialty field. CONCLUSION: The differences in
      practice style may have a potential effect on health systems as feminization of
      the medical profession increases.

PMID- 10955346
TI  - High dose, alternate day corticosteroids for systemic onset juvenile rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine the safety and efficacy of high dose alternate day (qod)
      prednisone as therapy in acute systemic onset JRA (SOJRA). METHODS: A
      retrospective chart review was performed of all active patients with SOJRA at our
      institutions who began high dose qod prednisone (n = 20; 9 male, 11 female; mean
      age of onset 6.5 yrs, range 1.2-18.6). Patients were followed for at least one
      year after initiation of high dose qod prednisone. Disease activity (fever, rash,
      active joint count, complete blood cell count, erythrocyte sedimentation rate,
      ESR) and possible side effects of treatment were assessed at each visit. RESULTS:
      Within a mean of 2.1 months (range 1-5), systemic features (fever, rash,
      serositis, coagulopathy) in all patients had resolved and there was significant
      improvement in laboratory indices of disease activity. Doses ranged from 1 to 5.8
      mg/kg qod (actual doses: 50-400 mg qod), with a mean of 3.2 mg/kg. No patient had
      to restart daily prednisone. The only major side effect was the development of
      mild cataracts in one patient. Height standard deviation scores (SDS) remained
      within normal range in all but 2 patients. Clinical improvement was maintained in
      all patients, as measured by lack of systemic symptoms, and decreased active
      joint count. Repeated measures of analysis of variance revealed significant
      improvement in all laboratory tests (white blood cell count, hemoglobin, platelet
      count, ESR) measured at 0, 6, and 12 months (p < 0.001). Nine of the 20 patients
      continued qod prednisone more than 12 months beyond the study period (mean 5.2
      yrs, range 3-8). The only additional side effects were a vertebral crush fracture
      in one patient and possible avascular necrosis in another. Height SDS did not
      change significantly over the 3 year period after the initiation of qod
      prednisone (p > 0.05). CONCLUSION: High dose qod prednisone appears to be
      effective in controlling the systemic features of SOJRA and was well tolerated.
      Side effects attributable to corticosteroids, including growth suppression, were
      minimal.

PMID- 10955348
TI  - Juvenile amyopathic dermatomyositis: results of a case finding descriptive
      survey.
AB  - OBJECTIVE: To review the clinical features of juvenile amyopathic dermatomyositis
      (ADM) to define an appropriate approach to its diagnosis and management. METHODS:
      Based on a review of published adult and pediatric cases, a prevalidated, peer
      reviewed, 3 page questionnaire was sent to all members of the Pediatric Section
      of the American College of Rheumatology and American Society for Pediatric
      Dermatology. RESULTS: Thirty-nine questionnaires were submitted for analysis.
      Twelve cases were excluded due to abnormal test results. Only one case met all
      criteria. Although 26 cases were incompletely investigated or had inadequate
      followup, they were not excluded, as all completed tests were normal. Two
      patients with incomplete data developed calcinosis. Of 27 patients not positively
      excluded, 10 were treated systemically, with 5 achieving remission, while 11/17
      untreated recovered spontaneously. At a mean followup of 32.8 months from disease
      onset none of the 27 patients has developed clinical myopathy. CONCLUSION: The
      classic skin changes of juvenile DM can occur in the absence of clinical muscle
      involvement. Physicians are not routinely performing electromyography, muscle
      biopsy, or magnetic resonance imaging in the assessment of these patients. A
      significant proportion of patients with ADM will remit without systemic therapy.
      Optimum treatment needs to be determined through controlled trials.

PMID- 10955347
TI  - Lyme arthritis in children and adolescents: outcome 12 months after initiation of
      antibiotic therapy.
AB  - OBJECTIVE: Lyme arthritis in children and adolescents due to infection with
      Borrelia burgdorferi responds well to intravenous and oral antibiotics, but
      nonresponders have been described with all antibiotic regimens tested and a
      standard therapy has not yet been established. We examined causes of the failure
      of antibiotic treatment in the presence of persistent organisms and autoimmune
      mechanisms. METHODS: A prospective multicenter study was carried out in 55
      children and adolescents with Lyme arthritis. RESULTS: There were significant
      differences between younger and older patients with pediatric Lyme arthritis.
      Younger patients were more likely to have fever at the onset of arthritis and to
      have acute or episodic arthritis. Older patients were more likely to have chronic
      arthritis, higher levels of IgG antibodies to B. burgdorferi (by ELISA and
      immunoblot), and a longer interval between antibiotic treatment and the
      disappearance of arthritis. Of 51 patients followed for at least 12 months after
      initiation of antibiotic treatment, 24% retained manifestations of the disease
      including arthritis (8 patients) and arthralgias (4 patients). These patients
      were predominantly female (9/12) and were significantly older than patients
      without residual symptoms. Patients who had received intraarticular steroids
      prior to antibiotic treatment required significantly more courses of antibiotic
      treatment and the time required for disappearance of the arthritis was longer.
      CONCLUSION: Pediatric Lyme arthritis is more benign in younger children. Lyme
      arthritis should be excluded as a possible cause of arthritis prior to the
      administration of intraarticular steroids.

PMID- 10955349
TI  - Catastrophic exacerbation of antiphospholipid syndrome after lung adenocarcinoma
      biopsy.
AB  - We describe a 60-year-old man with nephrotic syndrome due to a glomerular
      thrombotic microangiopathy caused by the antiphospholipid syndrome (APS)
      associated with a lung adenocarcinoma. Although no significant aggravation of APS
      was noted following renal biopsy, catastrophic exacerbation of APS occurred 3
      days after a lung adenocarcinoma biopsy while warfarin and prednisolone were
      being administered. The patient died of multiple organ failure 37 days after the
      lung adenocarcinoma biopsy. This case emphasizes the need for great caution for
      catastrophic exacerbation of malignancy associated APS following biopsy of the
      underlying malignancy.

PMID- 10955351
TI  - Leukocytoclastic vasculitis due to etanercept.
AB  - Recently etanercept, a soluble recombinant tumor necrosis factor receptor:Fc
      fusion protein, became available to treat patients with rheumatoid arthritis
      (RA). Among adverse reactions are cutaneous side effects, which occur in about 5%
      of patients. These have included mostly injection site reactions as well as
      urticarial reactions. We describe the first case of leukocytoclastic vasculitis
      associated with the use of etanercept in a patient with severe, deforming RA
      previously unresponsive to multiple therapies. Discontinuation of the drug led to
      complete resolution of the vasculitis.

PMID- 10955350
TI  - HLA-B27 associated spondyloarthropathy and severe ascending aortitis.
AB  - We describe a young woman who developed early and severe aortic regurgitation and
      subsequent aortitis with aneurysm formation requiring surgery.

PMID- 10955352
TI  - Acromioclavicular joint cyst: a presenting feature of full thickness rotator cuff
      tear.

PMID- 10955353
TI  - Fusobacterium osteomyelitis of the pubic symphysis in a healthy soccer player.

PMID- 10955354
TI  - Diagnostic criteria for Behcet's disease.

PMID- 10955355
TI  - Is there a place for large vessel disease in the diagnostic criteria of Behcet's
      disease?

PMID- 10955356
TI  - Elevated homocysteine levels in patients with Raynaud's syndrome.

PMID- 10955357
TI  - Solitary spinal cord sarcoid vasculitis.

PMID- 10955358
TI  - Better observational studies make better economic evaluations.

PMID- 10955359
TI  - 160 years of laminar flow--what have we learned?

PMID- 10955360
TI  - Oral quinine in ankylosing spondylitis: a randomized placebo controlled double
      blind crossover trial.

PMID- 10955361
TI  - Amtiperinuclear factor and antikeratin antibody: diagnostic use in a clinical
      laboratory setting.

PMID- 10955362
TI  - Sensitivity to change of the MOS SF-36 quality of life assessment questionnaire
      in patients with systemic lupus erythematosus taking immunosuppressive therapy.

PMID- 10955363
TI  - False positive treponemal test result in a patient with active systemic lupus
      erythematosus.

PMID- 10955364
TI  - Knee replacement is not contraindicated in the presence of secondary amyloidosis
      in patients with juvenile chronic arthritis.

PMID- 10955365
TI  - Poly(ADP-ribose) polymerase polymorphisms are not a genetic risk factor for
      systemic lupus erythematosus in German Caucasians.

PMID- 10955366
TI  - Three-dimensional intravascular ultrasonic volumetric quantification of stent
      recoil and neointimal formation of two new generation tubular stents.
AB  - Currently, several different designs of coronary stents are available. However,
      only a few of the new generation stents have been investigated in large
      randomized trials. Mechanical behavior of first-generation stents (Palmaz-Schatz,
      Gianturco-Roubin) may not be applied to the new designs. We investigated the
      chronic mechanical behavior (recoil) of 2 stents recently approved by the Food
      and Drug Administration (MULTILINK and NIR). Forty-eight patients with single
      stent implantation (23 MULTILINK and 25 NIR) were assessed by means of volumetric
      3-dimensional intravascular ultrasound analysis after the procedure and at 6
      month follow-up. In addition, volumetric assessment of neointimal formation was
      performed. No significant chronic stent recoil was detected in both groups (delta
      MULTILINK stent volume: +5.6+/-41 mm3 [p = NS] and delta NIR stent volume + 2.1+/
      26 mm3 [p = NS]). A similar degree of neointimal formation at 6 months was
      observed between the 2 stents (MULTILINK 46+/-31.9 mm3 vs NIR 39.9+/-27.6 mm3, p
      = NS). In conclusion, these 2 second-generation tubular stents did not show
      chronic recoil and appeared to promote similar proliferative response after
      implantation in human coronary arteries.

PMID- 10955367
TI  - Effects of total pathogen burden on coronary artery disease risk and C-reactive
      protein levels.
AB  - Infection and inflammation have been suggested to play roles in coronary artery
      disease (CAD). We hypothesized that: (1) CAD risk is associated with the
      aggregate number of pathogens (pathogen burden), and (2) increased pathogen
      burden is associated with elevated levels of C-reactive protein (CRP), a marker
      of inflammation. We evaluated 233 patients for CAD. Blood samples from each
      patient were tested for immunoglobulin-G (IgG) antibodies to cytomegalovirus
      (CMV), Chlamydia pneumoniae, hepatitis A virus (HAV), herpes simplex virus type 1
      (HSV-1) and HSV type 2 (HSV-2), and for the CRP levels. Of the 233 study
      subjects, 68% had evidence of CAD by coronary angiography. Although the
      prevalence of seropositivity for each pathogen tended to be higher in the
      patients with CAD than those without, only the association between CAD and
      seropositivity to HAV was significant in multivariate analysis. Over 75% of study
      subjects had been exposed to > or =3 of the 5 pathogens tested, and analysis
      determined that increasing pathogen burden was significantly associated with
      increasing CAD risk, even after adjustment for traditional CAD risk factors. The
      prevalence of CAD was 48%, 69%, and 85% in individuals with antibodies to < or =2
      pathogens, to 3 or 4 pathogens, and to 5 pathogens, respectively. A similar
      association between increasing pathogen burden and CRP levels was also found. The
      pathogen burden remained a significant predictor of CRP levels after multivariate
      analysis. Our data suggest that infection does play a role in the genesis of
      atherosclerosis. However, the risk posed by infection is related to the pathogen
      burden that may contribute to CAD through inflammatory responses.

PMID- 10955368
TI  - Clinical trial (GUSTO-1 and INJECT) evidence of earlier death for men than women
      after acute myocardial infarction.
AB  - Epidemiologic studies of acute myocardial infarction (AMI) have described gender
      differences in the time of death after infarction, with greater numbers of men
      dying before hospitalization than women. However, in controlled, hospital-based
      clinical trials, women die at higher rates than men. We hypothesized that
      evidence of a gender difference in the time of death following AMI may be found
      in controlled studies of hospitalized AMI patients. We performed a retrospective
      analysis of the Global Utilization of Streptokinase and Tissue Plasminogen
      Activator for Occluded Coronary Arteries (GUSTO-1) and International Joint
      Efficacy Comparison of Thrombolytics (INJECT) trial databases using logistic
      regression modeling and time-to-death analyses. The age-adjusted female-to-male
      odds ratio for mortality was 1.4 (95% confidence interval 1.3 to 1.5) in GUSTO-1
      and 1.5 (95% confidence interval 1.3 to 1.8) in INJECT. GUSTO-1 showed that among
      patients dying during the first 24 hours after symptom onset, men died an average
      of 1.7 hours earlier than women (p<0.001). This difference was due to earlier
      deaths among men < or =65 years of age. Furthermore, in GUSTO-1, the analysis of
      time to death in hour increments demonstrated that greater proportions of men
      died at earlier time points than women and a disproportionate number of early
      deaths occurred among younger men than among women of any age or older men. In
      INJECT, where time to death could only be analyzed in 1-day increments, no gender
      differences were evident. These results raise the possibility that the pattern of
      earlier death for men in thrombolytic clinical trials represents the continuation
      of a gender-specific mortality pattern that began before hospitalization. The
      death of a disproportionate number of men before hospitalization may represent an
      inherent gender bias for clinical studies enrolling only hospitalized patients.
      More high-risk men would be excluded from these studies than women because of
      death before hospitalization. Hence, gender comparisons of in-hospital mortality
      rates may artificially inflate values for women.

PMID- 10955369
TI  - Assessment of coagulation and platelet activation in coronary sinus blood induced
      by transcatheter coronary intervention for narrowing of the left anterior
      descending coronary artery.
AB  - Influences of recently developed methods for coronary intervention on hemostasis
      in the coronary circulation are unclear. The objective of this study was to
      investigate changes in coagulation and platelet activation in the coronary
      circulation induced by percutaneous transluminal coronary angioplasty (PTCA). We
      studied 35 patients with coronary heart disease who underwent elective PTCA to
      isolated stenotic narrowing of left coronary arteries. Seven patients received
      only PTCA, 12 underwent percutaneous transluminal rotational atherectomy (PTRA),
      and 16 underwent stent implantation. Blood samples were drawn from the coronary
      sinus immediately before and after as well as 4 and 24 hours after PTCA. Plasma
      levels of tissue factor (TF), thrombin-antithrombin III complex, plasminogen
      activator inhibitor (PAI)-1, tissue plasminogen activator (t-PA), beta
      thromboglobulin, and platelet factor 4 were measured by enzyme-linked
      immunosorbent assay. In all patients, TF levels in the coronary sinus blood
      showed significant increases 4 and 24 hours after PTCA and thrombin-antithrombin
      III complex levels showed significant increases 24 hours after PTCA. PAI-1 showed
      significant increases 24 hours after PTCA and t-PA showed significant increases 4
      and 24 hours after PTCA. Changes in levels of these markers by PTCA were similar
      among the 3 groups. In PTRA, levels of beta-thromboglobulin and platelet factor
      4, markers of platelet activation, increased immediately after the procedure and
      returned to baseline levels after 4 hours. PTCA induced increases in blood
      coagulation and fibrinolysis in the coronary circulation. PTRA caused a marked
      but transient activation of platelets. These changes may contribute to acute
      complications during the procedure.

PMID- 10955370
TI  - Effect of plasma insulin level on myocardial blood flow and its mechanism of
      action.
AB  - Considerable evidence suggests that coronary endothelium regulates myocardial
      blood flow and metabolism by elaborating vasoactive substances. The physiologic
      signals mediating this process are uncertain. To test the hypothesis that the
      process is influenced by physiologic variation in local insulin concentration, we
      examined the effect of direct intracoronary insulin infusion on myocardial blood
      flow and oxidative substrate metabolism in 10 patients with coronary heart
      disease. Ten men (aged 51 to 68 years) who were fasting received a 60-minute
      intracoronary infusion of insulin at a rate (10 mU/min) sufficient to raise
      coronary venous plasma insulin from 12+/-4 to 133+/-17 mU/ml without increasing
      the systemic insulin level. Local coronary hyperinsulinemia increased coronary
      sinus blood flow in every subject, from 50+/-4 to 61+/-6 ml/min (p<0.01). Insulin
      also increased myocardial uptake of glucose (from 6+/-1 to 17+/-6 mmol/min) and
      lactate (from 8+/-2 to 12+/-5 mmol/min), resulting in approximately 30% increase
      in total oxidative substrate uptake, but without increasing myocardial oxygen
      consumption (7.0+/-0.7 vs. 7.1+/-0.8 ml/min). Thus, physiologic elevation in the
      local plasma insulin concentration increases coronary blood flow in the absence
      of any increase in myocardial oxygen demand or consumption, suggesting a primary
      reduction in coronary tone, while simultaneously restraining the oxidation of
      imported substrates. These observations are consistent with insulin-mediated
      elaboration of vasoactive and/or paracrine factors within the coronary
      circulation.

PMID- 10955371
TI  - Relation of coronary artery size to one-year clinical events after new device
      angioplasty of native coronary arteries (a New Approach to Coronary Intervention
      [NACI] Registry Report).
AB  - The influence of vessel size on clinical and angiographic outcomes after new
      device angioplasty has not been well documented. We reviewed clinical and
      angiographic outcomes of 2,044 patients undergoing new device angioplasty of
      native vessels enrolled in the New Approaches to Coronary Interventions (NACI)
      Registry. Quantitative angiography was performed using standard methods. Patients
      were divided into 3 groups according to reference vessel diameter (RVD) (<2.75,
      2.75 to 3.25, and >3.25 mm). Patients with the smallest vessels had a higher
      incidence of diabetes (26% vs. 16%, p<0.01), multivessel disease (50% vs. 45%,
      p<0.01), left anterior descending coronary artery disease (61% vs. 39% p<0.01),
      and in general, more severe baseline lesion characteristics than patients with
      larger (>3.25 mm) vessels. Absolute baseline and final minimal lumen diameter
      (MLD) was also smaller in patients with RVD <2.75 mm despite similar final
      percent diameter stenosis. Although in-hospital events were similar, patients who
      underwent interventions in vessels <2.75 mm had an increased incidence of death
      (p<0.01), surgical revascularization (p<0.05), and target lesion
      revascularization (TLR) (p<0.01) at 1 year. Multivariate analysis by vessel size
      showed a stepwise increase in the risk of TLR by 1 year in patients with the
      smaller RVD (p = 0.0001) and the combined end point of 1 year death/Q wave
      myocardial infarction/TLR (p = 0.02). Thus, despite similar early clinical events
      among patients undergoing new device angioplasty, patients who underwent
      treatment of smaller vessels had a significantly increased risk of major adverse
      clinical events and particularly TLR by 1 year after new device angioplasty of
      native coronary arteries.

PMID- 10955372
TI  - Effect of atenolol and celiprolol on acetylcholine-induced coronary vasomotion in
      coronary artery disease.
AB  - Earlier studies have reported on the potentiated muscarinic vasoconstriction of
      intracoronary acetylcholine after metoprolol application in patients with
      coronary artery disease. The present study investigated the effect of celiprolol,
      atenolol, and placebo on acetylcholine-induced vasomotion in patients with
      coronary artery disease. Furthermore, direct effects on coronary vasomotion and
      on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of
      6.3x10(-7), 2.0x10(-6), and 6.3x10(-6) M) was given before and after double-blind
      celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3x12
      patients. Vasomotion was investigated by quantitative coronary angiography in
      proximal and distal segments of epicardial coronary arteries, and by the
      determination of the coronary resistance index based on Doppler-flow
      measurements. The investigated drugs had no direct affect on the diameter of the
      epicardial coronary arteries. However, celiprolol, in contrast to atenolol,
      significantly reduced systemic vascular resistance (change after atenolol: from
      1,855+/-308 to 2,161+/-550 dyne s cm(-5); celiprolol: 1,691+/-435 to 1,411+/-343
      dyne s cm(-5); and placebo: 1,722+/-215 to 1,710+/-213 dyne s cm(-5), p<0.001)
      and the coronary resistance index (change after atenolol: 2.52+/-3.58 to 2.86+/
      4.24; celiprolol: 2.70+/-1.55 to 2.49+/-2.26; and placebo: 1.97+/-1.35 to 1.92+/
      1.25, p<0.01). Celiprolol, atenolol, and placebo did not have different effects
      on acetylcholine-induced coronary vasomotion of epicardial conductance vessels
      (diminution of proximal lumen diameter before/after atenolol: 0.42+/-0.39/0.44+/
      0.39 mm; celiprolol: 0.32+/-0.26/0.30+/-0.24 mm; and placebo: 0.36+/-0.29/0.43+/
      0.40 mm) and of coronary resistance vessels (reduction of coronary resistance
      index before/after atenolol: 1.95 +/-4.74/ 1.92+/-3.74; celiprolol: 0.98+/
      0.73/1.41+/-1.50; and placebo: 1.16+/-1.29/1.16+/-1.04). In contrast to atenolol,
      celiprolol possesses vasodilative properties in systemic and coronary resistance
      vessels. There was no direct effect on the diameter of conductance vessels.
      Acetylcholine-induced coronary vasomotion both in conductance and resistance
      vessels was not influenced by the beta blockers that were studied. This suggests
      that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide
      related vasomotion.

PMID- 10955373
TI  - Effects of NK-104, a new hydroxymethylglutaryl-coenzyme reductase inhibitor, on
      low-density lipoprotein cholesterol in heterozygous familial
      hypercholesterolemia. Hokuriku NK-104 Study Group.
AB  - The clinical efficacy of NK-104, a novel and totally synthetic
      hydroxymethylglutaryl-coenzyme A reductase inhibitor, was assessed in 30 patients
      (men/women = 15/15, mean age 51 years) with heterozygous familial
      hypercholesterolemia. After a placebo phase of >4 weeks, NK-104 was given at an
      initial dose of 2 mg/day for 8 weeks, which was increased to 4 mg/day for a
      further 8 weeks. As a result of 2 mg/day of NK-104 treatment, mean +/- SD of
      total and low-density lipoprotein cholesterol levels decreased significantly
      (p<0.0001) from baseline, namely from 8.80+/-1.38 to 6.11+/-1.09 mmol/L (-31%)
      and from 6.81+/-1.52 to 4.09+/-1.03 mmol/L (-40%), respectively. They decreased
      further (p<0.0001) as a result of 4-mg/day administration, to 5.52+/-0.81 mmol/L
      (-37%) and 3.55+/-0.85 mmol/L (-48%), respectively. Changes in high-density
      lipoprotein cholesterol levels failed to reach statistical significance. Serum
      triglyceride levels decreased significantly (p<0.0001) from baseline as a result
      of 4 mg/day of NK-104, from 1.99+/-1.72 to 1.35+/-0.90 mmol/L (-23%). Serum
      apolipoprotein B, CII, CIII, and E levels significantly decreased: mean changes
      from baseline at the end of the study were -41% (p<0.0001), -27% (p<0.0001), -19%
      (p = 0.002), and -37% (p<0.0001), respectively. On the other hand, apolipoprotein
      AI and All levels significantly increased as a result of the treatment: + 10% (p
      = 0.002) and +6% (p = 0.008), respectively. There were no adverse events observed
      in either clinical or laboratory findings that could be attributed to the
      treatment. These results suggest that the potency of NK-104 appears to be dose
      dependent, and that NK-104 is safe and well tolerated in the treatment of
      patients with heterozygous familial hypercholesterolemia, and thus also provides
      a new therapeutic choice for subjects requiring lipid-modifying therapy.

PMID- 10955374
TI  - Potential risk of vasovagal syncope for motor vehicle driving.
AB  - Vasovagal syncope is the most common cause of syncope, but its risk for driving
      remains uncertain. We analyzed the clinical characteristics of patients who had
      syncope during driving and subsequently underwent the head-up tilt test (HUTT).
      Of the 245 consecutive patients undergoing HUTT, 23 (9%) had > or =1 episode of
      syncope during driving. HUTT was positive in 19 (group A) and negative in 4
      (group B) patients. No patient had structural heart disease. In group A, the
      driving incident occurred on the first syncope in 3 patients, and the other 16
      patients had 1 to 4 episodes of prior syncope not associated with driving. In
      group B, the driving incident occurred on the first syncope in 1 patient, and the
      other 3 patients had prior syncope (3 episodes in each) not associated with
      driving. Seven group A and 1 group B patients had 2 syncope-related driving
      incidents, and the remaining patients had only 1 syncope-related driving
      incident. The syncope-related driving incidents caused personal injury in 7 group
      A and 2 group B patients. One incident in 1 group A patient caused the death of
      another driver. After HUTT, all but 1 patient in group A received medical
      treatment and only 1 patient in group B received empirical beta-blocker therapy.
      During the follow-up of 51+/-26 months, 1 patient died and another was lost to
      follow-up. Of the remaining patients, 4 patients had recurrence of syncope and 2
      patients had presyncope in group A. One of these patients had another syncope
      related driving incident. No group B patient had syncope recurrence. A second
      etiology of syncope was never found in any patient. We conclude that vasovagal
      syncope during driving is not uncommon in patients referred for syncope
      evaluation. Early medical attention to patients with vasovagal syncope may help
      reduce syncope-related driving incidents.

PMID- 10955375
TI  - Meta-analysis of observed mortality data from all-controlled, double-blind,
      multiple-dose studies of losartan in heart failure. Losartan Heart Failure
      Mortality Meta-analysis Study Group.
AB  - Clinical studies of heart failure utilizing losartan, an angiotensin-II receptor
      antagonist, found that this drug is well tolerated and demonstrates hemodynamic,
      neurohormonal, and symptomatic improvement. To assess all-cause mortality in
      heart failure patients treated with losartan, a meta-analysis including 1,896
      patients was performed on 6 controlled, double-blind, multiple-dose studies,
      regardless of sample size or duration of follow-up. A combination of logarithmic
      (log) odds ratios with a continuity correction was utilized for the meta
      analysis. Treatment groups were comparable with regard to demographic
      characteristics, heart failure characteristics, and concomitant cardiovascular
      therapies. Concomitant use of open-label angiotensin-converting enzyme (ACE)
      inhibitors was not allowed in any study. The mean left ventricular ejection
      fraction obtained in individual studies ranged from 23% to 31%. Seven hundred
      forty patients were randomized to control therapy and 1,154 patients were
      randomized to losartan therapy. There were 36 deaths (3.12%) in the losartan
      groups compared with 47 in the control groups (6.35%) during the double-blind
      periods. The odds of dying in the losartan groups were 0.51 times (0.31 to 0.81)
      that of dying in the control groups (p = 0.004). In this analysis, treatment with
      losartan provided a beneficial effect upon survival. However, because the number
      of deaths in these studies is relatively small and the follow-up relatively
      short, a large confirmatory study is needed to assess the mortality benefit of
      losartan compared with an ACE inhibitor.

PMID- 10955377
TI  - Effect of general anesthesia on the severity of mitral regurgitation by
      transesophageal echocardiography.
AB  - The effect of general anesthesia on the severity of mitral regurgitation (MR) was
      examined in 43 patients with moderate or severe MR who underwent preoperative and
      intraoperative transesophageal echocardiography. Systolic blood pressure, mean
      arterial pressure, and left ventricular end-diastolic and end-systolic dimensions
      were significantly lower during the intraoperative study, reflecting altered
      loading conditions. The mean color Doppler jet area and mean vena contracta
      decreased and the mean pulmonary venous flow pattern changed from reversed to
      blunted, reflecting a significant reduction in the severity of MR. Overall, 22 of
      the 43 patients (51%) improved at least 1 MR severity grade when assessed under
      general anesthesia. Thus, intraoperative transesophageal echocardiography may
      significantly underestimate the severity of MR. A thorough preoperative
      assessment is preferable when deciding whether to perform mitral valve surgery.

PMID- 10955376
TI  - Severe mitral regurgitation due to mitral valve prolapse: risk factors for
      development, progression, and need for mitral valve surgery.
AB  - Patients with mitral valve prolapse (MVP) may develop severe mitral regurgitation
      (MR) and require valve surgery. Preliminary data suggest that high body weight
      and blood pressure might add to the irreversible factors of older age and male
      gender in increasing risk of these complications. Fifty-four patients with severe
      MR due to MVP were compared with 117 control subjects with uncomplicated MVP to
      elucidate factors independently associated with severe MR: the need for valve
      surgery and the cumulative risk of requiring mitral valve surgery. Patients with
      severe MR were older (p<0.00005), more overweight (p = 0.002), had higher
      systolic (p = 0.0003) and diastolic (p = 0.007) blood pressures, and were more
      likely to have hypertension (p = 0.0001) and to be men (p<0.001). In both groups,
      men had higher blood pressure and relative body weight than women. In
      multivariate analysis, older age was most strongly associated with MR; higher
      body mass index, hypertension, and gender were independent predictors of severe
      MR in analyses that excluded age. Among the 54 patients with severe MR, the 32
      (59%) who underwent mitral valve surgery during 11 years of follow-up were older,
      more overweight, and more likely to be hypertensive than those not requiring
      surgery. Among patients undergoing mitral valve surgery in 3 centers, mitral
      prolapse was the etiology in 25%, 67% of whom were men. Using these data and
      national statistics, we estimate that the gender-specific cumulative risk for
      requiring valvular surgery for severe MR in subjects with MVP is 0.8% in women
      and 2.6% in men before age 65, and 1.4% and 5.5% by age 75. Thus, subjects with
      MVP who are older, more overweight, and hypertensive are at greater risk for
      severe MR and valve surgery. Higher blood pressure and relative weight in men
      with MVP appear to contribute to the gender difference in risk for severe MR.

PMID- 10955378
TI  - Pulmonary artery hypertension in adult patients with symptomatic valvular aortic
      stenosis.
AB  - Pulmonary hypertension (PH) has been reported in patients with valvular aortic
      stenosis (AS) and has been found to be associated with a more severe clinical
      picture and a poor prognosis after aortic valve replacement. The aim of this
      study was to assess the prevalence of PH in adult patients with symptomatic AS
      undergoing cardiac catheterization, and to evaluate the relation between
      pulmonary artery (PA) systolic pressure and hemodynamic and clinical variables to
      further clarify the pathogenetic mechanisms. We assessed right-sided heart
      hemodynamics during cardiac catheterization in 388 patients with symptomatic
      isolated or predominant AS. PA systolic pressure between 31 and 50 mm Hg was used
      to define mild to moderate PH, whereas PA systolic pressure >50 mm Hg was used to
      define severe PH. PA systolic pressure showed no significant difference according
      to age and sex, although it was significantly higher in patients in New York
      Heart Association functional classes III and IV and in patients with coexistent
      systemic hypertension than in the others. PH was absent in 136 patients (35%,
      group 1), mild to moderate in 196 patients (50%, group 2), and severe in 58
      patients (15%, group 3). Only the prevalence of overt heart failure was
      significantly higher in group 3 patients. AS severity was similar among the 3
      groups, and PA systolic pressure showed no relation to aortic valve area in the
      entire population. Also, a poor correlation was found between PA pressure and
      left ventricular (LV) ejection fraction (r = -0.28), with several patients having
      moderate or severe PH despite a preserved LV systolic function. PA systolic
      pressure significantly correlated with LV end-diastolic pressure (r = 0.50) and
      with PA wedge pressure (r = 0.84). Furthermore, transpulmonary pressure gradient,
      an index of resistance across the pulmonary vascular bed (obtained as the
      difference between PA mean and PA wedge pressure), was significantly higher in
      patients with PH, especially in those with a marked increase in PA systolic
      pressure, suggesting a reactive component of PH.

PMID- 10955379
TI  - Echocardiographic dimensions and function in adults with primary growth hormone
      resistance (Laron syndrome).
AB  - Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no
      GH signal transmission, and thus, no generation of circulating insulin-like
      growth factor-I (IGF-I), and should serve as a unique model to explore the
      controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac
      dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a
      mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls
      (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by
      echocardiography at rest, following exercise, and during dobutamine
      administration. Left ventricular (LV) septum, posterior wall, and end-diastolic
      diameter were significantly reduced in untreated patients with LS compared with
      the control group (p<0.05 for all). Systolic Doppler-derived parameters,
      including LV stroke volume, stroke index, cardiac output, and cardiac index, were
      significantly lower (p<0.05 for all) than in the control subjects, whereas LV
      diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E
      deceleration time, were similar in both groups. LV ejection fraction at rest as
      well as the stress-induced increment of the LV ejection fraction were similar in
      both groups. Our results show that untreated patients with long-term IGF-I
      deficiency have reduced cardiac dimensions and output but normal LV ejection
      fraction at rest and LV contractile reserve following stress.

PMID- 10955380
TI  - Indium-111 monoclonal antimyosin cardiac scintigraphy in men with idiopathic
      dilated cardiomyopathy.
AB  - This study examined the prognostic value and the evolution of the heart-to-lung
      ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis
      of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA
      occurs when the myocytes become irreversibly damaged. The study included 29 men
      with IDC followed up for 3 years. The diagnosis was verified by endomyocardial
      biopsy in all patients. Patients who survived beyond 1 year were restudied.
      Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression
      analysis revealed that MAA and New York Heart Association class were independent
      predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval
      1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003),
      respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York
      Heart Association class was >11. When these patients were divided into those with
      chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]),
      baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p =
      NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake
      was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of
      group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high
      heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients
      with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time
      in subacute IDC and remains stable in chronic IDC.

PMID- 10955381
TI  - Homograft insertion for pulmonary regurgitation after repair of tetralogy of
      fallot improves cardiorespiratory exercise performance.
AB  - Surgical repair of tetralogy of Fallot (TOF) with reconstruction of the right
      ventricular (RV) outflow tract invariably results in pulmonary regurgitation.
      Chronic pulmonary regurgitation has been associated with RV dysfunction and
      decreased exercise performance. The present study assessed the influence of
      pulmonary valve replacement (PVR) for severe pulmonary regurgitation after
      previous TOF repair on cardiorespiratory exercise performance and RV function.
      Eighteen patients, between the ages of 8 and 18 years, underwent an exercise test
      and a cardiac magnetic resonance imaging scan at least 1 year after PVR. The
      exercise data were compared with those obtained from 24 age-matched normal
      controls and 27 age-matched patients with repaired TOF and a moderate degree of
      pulmonary regurgitation. A subgroup of 11 patients had an exercise test performed
      before and after PVR. Cardiopulmonary exercise performance was evaluated by
      determination of the ventilatory anaerobic threshold (VAT) and by the steepness
      of the slope of oxygen uptake versus exercise intensity (SVO2). After PVR there
      was a significant increase in VAT (86+/-11% before to 106.9+/-14% after, p =
      0.03) and in SVO2 (1.71+/-0.47 to 2.3+/-0.39, p = 0.004). In patients examined
      after PVR, the VAT and SVO2 values were not significantly different from the
      values in the normal controls (104+/-15% [p>0.05] and 2.03+/-0.77 after PVR vs.
      2.42+/-0.68 [p>0.25], respectively). In contrast, patients with repaired TOF and
      a moderate degree of pulmonary regurgitation had a significantly lower VAT (86+/
      11%, p<0.05) and SVO2 (1.8+/-0.74 vs. 2.42+/-0.68, p<0.05) than normal controls.
      Magnetic resonance imaging studies revealed residual RV dilatation and
      dysfunction. However, there was no correlation between RV dilatation and RV
      dysfunction and aerobic exercise capacity. It is concluded that aerobic exercise
      capacity substantially improves after PVR for severe pulmonary regurgitation
      after previous TOF repair. Although the right ventricle remains significantly
      dilated and hypocontractile, there is no relation between RV function and
      exercise performance.

PMID- 10955382
TI  - Progression of atherosclerosis at one-year follow-up seen with volumetric
      intravascular ultrasound in femoropopliteal arteries.
AB  - Volume measurements derived from intravascular ultrasound (IVUS) images assessed
      with an automated contour analysis system are accurate and reproducible. However,
      it is unknown to what extent plaque volume may change at follow-up. Therefore,
      the purpose of this longitudinal study is to examine whether IVUS is a sensitive
      means to identify progression of atherosclerosis and its derived primary end
      point plaque volume at 1-year follow-up. Patients (n = 11) undergoing
      percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery were
      studied with IVUS immediately after PTA in the same session and at 1-year follow
      up. Matched, well-identified vascular segments (3 to 4 cm in length), not
      subjected to PTA, imaged at baseline and after 1-year follow-up, were used for
      calculation of the longitudinal change in lumen, vessel and plaque volume, and
      mean plaque thickness. The median length of the selected vascular segments was 4
      cm. At follow-up (12+/-2 months) a nonsignificant increase in lumen volume (2.3+/
      11%), vessel volume (2.0+/-7.0%), and plaque volume (3.0+/-5.1%) was seen; the
      mean plaque thickness increase was 2.2+/-5.6%. In conclusion, progression of
      atherosclerosis implies changes in plaque and vessel volume, resulting in lumen
      volume change. This observation has important implications for future clinical
      trials aimed at monitoring the effect of pharmacologic agents on the progression
      and/or regression of atherosclerosis.

PMID- 10955383
TI  - Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome,
      systemic hypertension, and neither condition.
AB  - Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing
      abnormalities, arterial hypertension, and an increased number of cardiovascular
      events. Sympathetic activity is increased during nocturnal apneic episodes, which
      may mediate the cardiovascular complications of sleep apnea. We studied 15 male
      subjects with obstructive sleep apnea syndrome and associated hypertension, 54
      subjects with mild to moderate essential hypertension, and 25 healthy
      normotensive men. Cardiovascular autonomic control was assessed using frequency
      domain measures of heart rate variability (HRV) during a controlled breathing
      test and during orthostatic maneuver. Compared with normotensive and hypertensive
      groups, total power and low- and high-frequency components of HRV during
      controlled breathing were significantly (analysis of variance, p<0.0001) lower in
      the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change
      in total power of HRV was different between the 3 groups (analysis of variance, p
      = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/
      12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/
      1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome.
      According to multivariate regression analysis, age and sleep apnea were the major
      independent determinants of HRV. This study found that an abnormal response to
      autonomic nervous tests characterizes hypertension in overweight subjects with
      obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or
      supersaturation of the end-organ receptors by excessive and prolonged sympathetic
      stimulation. Our results also show the reduced response of orthostatic maneuver
      and controlled breathing in the hypertensive group compared with the normotensive
      group.

PMID- 10955384
TI  - National use of the transesophageal echocardiographic-guided approach to
      cardioversion for patients in atrial fibrillation.
AB  - Transesophageal echocardiographic (TEE)-guided cardioversion of patients in
      atrial fibrillation (AF) of >2 days' duration is used as an alternative to
      conventional therapy. The purpose of this study was to investigate practice
      patterns employed for stroke prophylaxis in patients with AF who underwent
      cardioversion, and to determine the relative use of conventional and TEE-guided
      management strategies. We forwarded regionally stratified survey questionnaires
      to 947 clinical practices within the United States. The 10-question questionnaire
      queried demographic and clinical practice volumes and practices for managing
      patients with AF who underwent cardioversion. In addition, we used historical
      data to determine longitudinal use patterns of the TEE-guided approach for a
      large institution over 7 years. The 197 completed and returned surveys yielded a
      return rate of 20.8%. The TEE-guided approach was employed in approximately 12%
      of total cardioversions, but 75% of practices indicated that they employed
      transesophageal echocardiography only occasionally. The TEE-guided approach was
      associated with community size (r = 0.19; p<0.008), type of practice (r = 0.26; p
      = 0.001), total use of transesophageal echocardiography (r = 0.48; p<0.001), and
      volume of cardioversions (r = 0.28; p<0.001). Importantly, there was little
      consensus on the most appropriate clinical indications for TEE-guided
      cardioversions, and the proportions of TEE-guided cardioversion to total number
      of electrical cardioversions remained stable over 7 years. Practice volume and
      physician training may be the most important variables in the adoption of the TEE
      approach.

PMID- 10955385
TI  - Echocardiographic quantification of regional left ventricular wall motion with
      color kinesis.
AB  - Echocardiographic assessment of regional systolic left ventricular function is
      usually performed qualitatively and depends on investigator experience. In this
      study, we investigated a new method for quantifying regional systolic wall motion
      based on color kinesis. In this study, regional systolic wall motion velocity
      (Vsys) was determined by dividing end-systolic color width by systolic time. High
      regional wall motion velocity (Vhigh) was determined by dividing the width of the
      widest color by its duration of 40 ms. First, in vitro measurements with an
      acrylic glass model were obtained; these demonstrated a high correlation between
      echocardiographically determined and real "wall motion velocities" (R = 0.99,
      p<0.001, R2 = 0.99). Then, 17 healthy, young persons were examined, and normal
      values for each left ventricular wall segment (16-segment model) were determined.
      The mean Vsys and Vhigh of all 272 wall segments were 2.3+/-0.6 and 7.4+/-1.8
      cm/s, respectively. Finally, in 12 patients with coronary artery disease and
      prior myocardial infarction, Vsys and Vhigh of each left ventricular wall segment
      were determined and compared with conventional echocardiographic wall motion
      analysis using the usual 4-grade score system. Analysis of data showed that
      quantitative color kinesis measurements demonstrated significantly lower velocity
      values in pathologic than in normal wall segments (Mann-Whitney U test, p<0.05).
      Measurements discriminated between pathologic and normal wall motion, with an
      accuracy of 89% for Vsys and 83% for Vhigh (chi-square test, p<0.05). To
      summarize, in this first study, measurements of regional wall motion velocities
      with color kinesis demonstrated reliable results for the quantification of
      regional left ventricular systolic function.

PMID- 10955386
TI  - Elevated systolic blood pressure as a cardiovascular risk factor.
AB  - This paper reviews the evolution of attitudes toward the treatment and diagnosis
      of hypertension. In particular, there is a growing realization that elevated
      systolic pressure may be a more valuable measurement in evaluating and
      controlling hypertension than is generally acknowledged. A large number of
      epidemiologic studies in a wide variety of populations have revealed that
      systolic blood pressure exerts a stronger influence than diastolic blood
      pressure. The largest of these, the Framingham Heart Study, showed that in
      subjects with systolic hypertension, diastolic blood pressure was only weakly
      related to the risk of cardiovascular events, but in those with diastolic
      hypertension, the risk of these events was strongly influenced by the level of
      systolic pressure. Furthermore, cardiovascular event rates were found to increase
      steeply with systolic pressure and were higher in cases of isolated systolic
      hypertension than diastolic hypertension. Clinical trials produced similar
      results, again suggesting that a greater reliance should be placed on systolic
      pressure in evaluating the risk of cardiovascular problems. This review concludes
      that the health community needs to be reeducated to consider the importance of
      systolic and diastolic blood pressure in assessing appropriate management
      strategies for hypertensive patients.

PMID- 10955387
TI  - Comparison of time course of target lesion revascularization following successful
      saphenous vein graft angioplasty versus successful native coronary angioplasty.
AB  - We studied 1,267 patients with 2,186 saphenous vein graft (SVG) lesions to
      determine the time course of target lesion revascularization (TLR) after
      successful SVG angioplasty. We found that the time course of TLR in SVG appears
      prolonged, with only 54% occurring within the first 6 months and continued TLR
      even after 1 year.

PMID- 10955388
TI  - Prognostic value of exercise echocardiography in women in the community setting.
AB  - Treadmill stress echocardiography was performed in 1,136 women with known or
      suspected coronary artery disease whose clinical course was then evaluated a mean
      of 33 months later (range 12 to 60). The strongest predictor of an adverse
      outcome was the presence of a resting or an exercise-induced wall motion
      abnormality.

PMID- 10955389
TI  - Significance of newly acquired negative T waves after interruption of paroxysmal
      reentrant supraventricular tachycardia with narrow QRS complex.
AB  - Sixty-three patients with paroxysmal supraventricular tachycardia were studied
      and 25 patients (39%) showed newly acquired negative T waves after tachycardia
      termination. Silent coronary artery disease could not be found in about 90% of
      these patients; moreover, age, sex, organic heart disease, and tachycardia
      duration and rate did not predict the appearance of negative T waves.

PMID- 10955390
TI  - Early repolarization: an electrocardiographic predictor of enhanced aerobic
      fitness.
AB  - The presence or absence of early repolarization on the electrocardiogram at rest
      was correlated with aerobic exercise capacity in healthy volunteers from the
      Baltimore Longitudinal Study of Aging. Patients with early repolarization had
      both longer treadmill exercise duration and higher peak oxygen consumption than
      age-and gender-matched control subjects.

PMID- 10955391
TI  - Cyclosporine versus tacrolimus (FK 506) for prevention of cardiac allograft
      vasculopathy.
AB  - This study prospectively compared the impact of cyclosporine A and tacrolimus on
      the development of cardiac allograft vasculopathy. By using serial intravascular
      ultrasound examinations, a trend toward a more pronounced progression was noted
      in the tacrolimus group in the first year after heart transplantation.

PMID- 10955392
TI  - Testosterone enhances flow-mediated brachial artery reactivity in men with
      coronary artery disease.
AB  - Acute administration of high-dose testosterone in men with coronary artery
      disease improves endothelial function.

PMID- 10955393
TI  - Case 2: a patient with systemic hypertension and diabetes mellitus.

PMID- 10955394
TI  - Case 3: a patient with syncope.

PMID- 10955395
TI  - Non-English acronyms have to be explained in their native languages.

PMID- 10955396
TI  - Mechanism of cardioprotective effect and the choice of alcoholic beverage.

PMID- 10955397
TI  - Aortic valve sclerosis and aerobic exercise.

PMID- 10955398
TI  - The smoking gun?

PMID- 10955399
TI  - Urban air pollution and lung cancer in Stockholm.
AB  - We conducted a population-based case-control study among men 40-75 years of age
      encompassing all cases of lung cancer 1985-1990 among stable residents of
      Stockholm County 1950-1990. Questionnaires to subjects or next-of-kin (primarily
      wives or children) elicited information regarding smoking and other risk factors,
      including occupational and residential histories. A high response rate (>85%)
      resulted in 1,042 cases and 2,364 controls. We created retrospective emission
      databases for NOx/NO2 and SO2 as indicators of air pollution from road traffic
      and heating, respectively. We estimated local annual source-specific air
      pollution levels using validated dispersion models and we linked these levels to
      residential addresses using Geographical Information System (GIS) techniques.
      Average traffic-related NO2 exposure over 30 years was associated with a relative
      risk (RR) of 1.2 (95% confidence interval 0.8-1.6) for the top decile of
      exposure, adjusted for tobacco smoking, socioeconomic status, residential radon,
      and occupational exposures. The data suggested a considerable latency period; the
      RR for the top decile of average traffic-related NO2 exposure 20 years previously
      was 1.4 (1.0-2.0). Little association was observed for SO2. Occupational exposure
      to asbestos, diesel exhaust, and other combustion products also increased the
      risk of lung cancer. Our results indicate that urban air pollution increases lung
      cancer risk and that vehicle emissions may be particularly important.

PMID- 10955400
TI  - Socioeconomic status and survival of persons with AIDS before and after the
      introduction of highly active antiretroviral therapy. Lazio AIDS Surveillance
      Collaborative Group.
AB  - We estimated the AIDS survival by neighborhood socioeconomic status before (1993
      1995) and after (1996-1997) the introduction of highly active antiretroviral
      therapy in Rome, Italy, in a retrospective cohort of persons with AIDS followed
      through July 31, 1998. Participants included 1,474 persons with AIDS residing in
      Rome who were diagnosed in 1993-1997. We calculated hazard ratios (HRs) of death
      for two diagnostic periods (before and after highly active antiretroviral therapy
      was introduced) by neighborhood socioeconomic status categorized into four levels
      (level I = highest socioeconomic status), using the Cox model and adjusting for
      gender, age, intravenous drug use, CD4 cell count at diagnosis, AIDS-defining
      disease, and hospital of diagnosis. Thirty-four per cent of persons with AIDS (N
      = 503) had survived as of mid-1998. For persons with AIDS diagnosed in 1993-1995,
      we found little difference in the risk of death by neighborhood socioeconomic
      status. For 1996-1997, the risk of death was greater for persons with lower
      neighborhood socioeconomic status, especially for levels III and IV [HR = 2.81
      (95% confidence interval = 1.38-5.76), and HR = 2.55 (95% confidence interval =
      1.27-5.14), respectively, compared with level I]. Stratified analyses showed that
      the greatest difference was found for women and drug users. In conclusion, even
      in a country with universal health coverage that provides therapy at no cost,
      differences in survival of persons with AIDS have emerged by neighborhood
      socioeconomic status since highly active antiretroviral therapy was introduced.
      Inequalities in health-care access or in medical management, or poor adherence to
      treatment, could explain the observed heterogeneity.

PMID- 10955401
TI  - Effect of air pollution on preterm birth among children born in Southern
      California between 1989 and 1993.
AB  - We evaluated the effect of air pollution exposure during pregnancy on the
      occurrence of preterm birth in a cohort of 97,518 neonates born in Southern
      California. We used measurements of carbon monoxide (CO), nitrogen dioxide,
      ozone, and particulate matter less than 10 microm (PM10) collected at 17 air
      quality-monitoring stations to create average exposure estimates for periods of
      pregnancy. We calculated crude and adjusted risk ratios (RRs) for premature birth
      by period-specific ambient pollution levels. We observed a 20% increase in
      preterm birth per 50-microg increase in ambient PM10 levels averaged over 6 weeks
      before birth [RRcrude = 1.20; 95% confidence interval (CI) = 1.09-1.33] and a 16%
      increase when averaging over the first month of pregnancy (RRcrude = 1.16; 95% CI
      = 1.06-1.26). PM10 effects showed no regional pattern. CO exposure 6 weeks before
      birth consistently exhibited an effect only for the inland regions (RRcrude =
      1.13; 95% CI = 1.08-1.18 per 3 parts per million), and during the first month of
      pregnancy, the effect was weak for all stations (RRcrude = 1.04; 95% CI = 1.01
      1.09 per 3 parts per million). Exposure to increased levels of ambient PM10 and
      possibly CO during pregnancy may contribute to the occurrence of preterm births
      in Southern California.

PMID- 10955402
TI  - Does alcohol increase the risk of preterm delivery?
AB  - We evaluated the association between alcohol intake during pregnancy and preterm
      delivery. Women attending routine antenatal care at Aarhus University Hospital,
      Denmark, from 1989-1991 and 1992-1996 were eligible. We included 18,228 singleton
      pregnancies in the analyses. We obtained prospective information on alcohol
      intake at 16 and 30 weeks of gestation, other lifestyle factors, maternal
      characteristics, and obstetrical risk factors from self-administered
      questionnaires and hospital files. For women with alcohol intake of 1-2, 3-4, 5
      9, and > or =10 drinks/week the risk ratio (RR) of preterm delivery was 0.91 (95%
      CI = 0.76-1.08), 0.86 (95% CI = 0.64-1.15), 0.89 (95% CI = 0.52-1.52), and 2.93
      (95% CI = 1.52-5.63), respectively, compared with intake of <1 drink/week at 16
      weeks gestation, and 0.69 (95% CI = 0.56-0.86), 0.82 (95% CI = 0.60-1.13), 0.97
      (95% CI = 0.58-1.64), and 3.56 (95% CI = 1.78-7.13) at 30 weeks. Adjustment for
      smoking habits, caffeine intake, age, height, pre-pregnant weight, marital
      status, occupational status, education, parity, chronic diseases, previous
      preterm delivery, mode of initiation of labor, and sex of the child did not
      change the conclusions, nor did restriction of the highest intake group to women
      drinking 10-14 drinks/week (RR = 3.41 (1.71-6.81) at 16 weeks and RR = 3.47 (1.64
      7.35) at 30 weeks).

PMID- 10955403
TI  - Risk indicators for reported over-exertion back injuries among female nursing
      personnel.
AB  - We conducted a case-referent study to identify and quantify work-related and non
      work-related risk indicators for reported over-exertion back injuries among
      nursing personnel. The source population was all nursing personnel employed in
      the Stockholm County hospitals during a 32-month period. The 240 cases and 614
      referents completed questionnaires about occupation, type of clinic, working
      hours, shift work, patient transfers, perceived exertion, back pain, prior back
      injury, job strain, body mass index (BMI), smoking, immigrant status, physical
      training, and self-rated fitness. The highest relative risks (RR) were observed
      for work-related factors: working at an orthopedic clinic (RR = 5.2; 95% CI = 2.7
      10.2), > or =1 patient transfer/shift (RR = 2.7; 95% CI = 1.6-4.5), and working
      full-time (RR = 2.4; 95% CI = 1.6-3.6). Training in the use of transfer devices,
      and regular use of transfer devices, reduced the relative risk from patient
      transfer. Among the non-work-related factors, only body mass index > or =25 kg/m2
      and immigrant status was associated with a slight increase in relative risk.

PMID- 10955404
TI  - A population-based case-control study of farming and breast cancer in North
      Carolina.
AB  - We examined the role of farming and pesticide exposure among 862 cases and 790
      controls in a population-based, case-control study of breast cancer conducted in
      North Carolina between 1993 and 1996. We obtained exposure information through
      personal interview. Increasing duration of farming was inversely associated with
      breast cancer risk; odds ratios (95% confidence intervals) were 1.2 (0.8-1.7),
      0.8 (0.5-1.2), 0.7 (0.5-1.1), and 0.6 (0.4-0.9) for 1-10, 11-17, 18-23, and >23
      years of farming, respectively, relative to nonfarmers. Inverse associations
      persisted when farming was restricted to calendar time periods of 2,2-bis(p
      chlorophenyl)- 1,1,1-trichloroethane (DDT) use or to farming at ages 9-16. Among
      women who farmed, odds ratios (ORs) were elevated for those who reported being
      present in fields during or shortly after pesticide application (OR = 1.8, 95% CI
      = 1.1-2.8) and for those who reported not using protective clothing while
      applying pesticides (OR = 2.0; 95% CI = 1.0-4.3), but not among those who
      reported using protective clothing (OR = 0.8; 95% CI = 0.4-1.8). We conclude that
      residence or work on farms may be associated with a reduced risk of breast
      cancer. Nevertheless, our results suggest a possible increased risk of breast
      cancer among a subgroup of farming women who were most likely to be exposed to
      pesticides.

PMID- 10955405
TI  - Occupational risks for lung cancer among nonsmokers.
AB  - We conducted a case-control study in 12 European study centers to evaluate the
      role of occupational risk factors among nonsmokers. We obtained detailed
      occupational histories from 650 nonsmoking cases (509 females/141 males) and
      1,542 nonsmoking controls (1,011 females/531 males). On the basis of an a priori
      definition of occupations and industries that are known (list A) or suspected
      (list B) to be associated with lung carcinogenesis, we calculated odds ratios
      (ORs) for these occupations, using unconditional logistic regression models and
      adjusting for sex, age, and center effects. Among nonsmoking men, an excess
      relative risk was observed among those who had worked in list-A occupations [OR =
      1.52; 95% confidence interval (C) = 0.78-2.97] but not in list-B occupations (OR
      = 1.05; 95%), CI = 0.60-1.83). Among nonsmoking women, there was an elevation of
      risk for list-A occupations (OR = 1.50; 95% CI = 0.49-4.53), although this
      estimate was imprecise, given that less than 1% of cases and controls were
      exposed. Exposure to list-B occupations was associated with an increase in
      relative risk (OR = 1.69; 95% CI = 1.09-2.63) in females, but not in males. Women
      who had been laundry workers or dry cleaners had an OR of 1.83 (95% CI = 0.98
      3.40). Our findings confirm that certain occupational exposures are associated
      with an increased risk for lung cancer among both female and male nonsmokers;
      however, knowledge on occupational lung carcinogens is biased toward agents to
      which mainly men are exposed.

PMID- 10955406
TI  - Exposure to electromagnetic fields and risk of central nervous system disease in
      utility workers.
AB  - Occupational exposure to electromagnetic fields has been associated with
      neurological diseases such as amyotrophic lateral sclerosis, senile dementia,
      Parkinson disease, and Alzheimer disease. I studied the incidence of central
      nervous system diseases in 30,631 persons employed in Danish utility companies
      between 1900 and 1993. I linked the cohort to the nationwide, population-based
      Danish National Register of Patients and compared the numbers of cases of these
      diseases observed between 1978 and 1993 with the corresponding rates in the
      general population. In addition I fit to the data on utility workers a
      multiplicative Poisson regression model in relation to estimated levels of
      exposure to 50-Hz electromagnetic fields. Overall, there was an increase in risk
      for senile dementia and motor neuron diseases combined. The incidences of
      Parkinson disease, Alzheimer disease, and other diseases of the central nervous
      system were essentially unrelated to exposure to electromagnetic fields. A
      decreased risk of epilepsy compared with the general population probably reflects
      a healthy worker effect; I observed an increased risk of epilepsy based on
      internal comparisons. The increased risk for senile dementia and motorneuron
      diseases may be associated with above-average levels of exposure to
      electromagnetic fields.

PMID- 10955407
TI  - A sensitivity analysis to separate bias due to confounding from bias due to
      predicting misclassification by a variable that does both.
AB  - Variables that predict misclassification of exposure, outcome, or a confounder
      cannot be controlled by techniques that adjust for predictors of risk. They must
      be controlled by external adjustments. We confronted an analysis in which a
      variable predicted misclassification of the exposure and of a confounder. The
      same variable confounded the exposure-outcome relation. The analysis focused on
      the relation between less-than-definitive therapy and breast cancer mortality in
      the 5 years after diagnosis. Receipt of less-than-definitive prognostic
      evaluation predicted misclassification of definitive therapy (the exposure) and
      stage (a confounder). Prognostic evaluation also confounded the therapy-breast
      cancer mortality relation. We used a sensitivity analysis to separate the
      misclassification biases from the confounding bias. The relative hazard
      associated with less-than-definitive therapy in the original multivariable model
      equaled 1.75 (95% confidence interval = 1.02-3.00). The median estimate in 2,500
      repetitions of the sensitivity analysis was a relative hazard of 1.64, and 90% of
      the estimates fell between 1.47 and 1.83. The sensitivity analysis suggests that
      less-than-definitive therapy confers an excess relative hazard of breast cancer
      mortality in the 5 years after diagnosis. The original analysis, which adjusted
      for confounding by prognostic evaluation but not its misclassification biases,
      overestimated the relative hazard.

PMID- 10955408
TI  - Marginal structural models and causal inference in epidemiology.
AB  - In observational studies with exposures or treatments that vary over time,
      standard approaches for adjustment of confounding are biased when there exist
      time-dependent confounders that are also affected by previous treatment. This
      paper introduces marginal structural models, a new class of causal models that
      allow for improved adjustment of confounding in those situations. The parameters
      of a marginal structural model can be consistently estimated using a new class of
      estimators, the inverse-probability-of-treatment weighted estimators.

PMID- 10955409
TI  - Marginal structural models to estimate the causal effect of zidovudine on the
      survival of HIV-positive men.
AB  - Standard methods for survival analysis, such as the time-dependent Cox model, may
      produce biased effect estimates when there exist time-dependent confounders that
      are themselves affected by previous treatment or exposure. Marginal structural
      models are a new class of causal models the parameters of which are estimated
      through inverse-probability-of-treatment weighting; these models allow for
      appropriate adjustment for confounding. We describe the marginal structural Cox
      proportional hazards model and use it to estimate the causal effect of zidovudine
      on the survival of human immunodeficiency virus-positive men participating in the
      Multicenter AIDS Cohort Study. In this study, CD4 lymphocyte count is both a time
      dependent confounder of the causal effect of zidovudine on survival and is
      affected by past zidovudine treatment. The crude mortality rate ratio (95%
      confidence interval) for zidovudine was 3.6 (3.0-4.3), which reflects the
      presence of confounding. After controlling for baseline CD4 count and other
      baseline covariates using standard methods, the mortality rate ratio decreased to
      2.3 (1.9-2.8). Using a marginal structural Cox model to control further for time
      dependent confounding due to CD4 count and other time-dependent covariates, the
      mortality rate ratio was 0.7 (95% conservative confidence interval = 0.6-1.0). We
      compare marginal structural models with previously proposed causal methods.

PMID- 10955410
TI  - A case-control etiologic study of microcephaly.
AB  - We studied the possible environmental factors in the origin of microcephaly by
      comparing the exposures of 109 infants with isolated microcephaly with those of
      two matched population controls, in addition to those of 812 patient controls
      (that is, infants with Down syndrome). Cases and patient controls were selected
      from the large population-based dataset of the Hungarian Case-Control
      Surveillance of Congenital Abnormalities registered between 1980 and 1996,
      whereas matched population controls were selected from the national birth
      registry. We found that there were more females than males among cases with
      isolated microcephaly. Evaluation of birth weight and gestational age indicated
      intrauterine growth retardation among microcephalic patients. The use of
      clotrimazole was higher among mothers in the matched population control group
      than among mothers of cases. Maternal use of a large dose (about 6 mg per day) of
      folic acid and more than 50 mg per day of iron during pregnancy was associated
      with a 40-50% decrease in microcephaly. Thus, the pharmacological doses of folic
      acid and iron may have some preventive effect against isolated primary
      microcephaly.

PMID- 10955411
TI  - Handedness and mortality: a follow-up study of Danish twins born between 1900 and
      1910.
AB  - The declining prevalence of left-handed individuals with increasing age has led
      to two main avenues of hypotheses; the association is due either (1) to a birth
      cohort effect and/or an age effect caused by a switch to right-handedness with
      advancing age or (2) to mortality selection that reduces survival in left-handed
      individuals, or both. It is uncertain whether a cohort or age effect can explain
      the decline in age-related prevalence, and conflicting evidence exists in favor
      of the mortality hypothesis. We compared mortality in a subgroup of 118 opposite
      handed twin pairs by counting in how many instances the right-handed twin died
      first. There was no evidence of differential survival between right-handed and
      non-right-handed individuals in the entire 1900-1910 cohort. With respect to the
      number of right-handed twins who died first, there was no material disadvantage
      among those who were not right-handed. In 60% (95% confidence interval = 49.0
      71.5%) of dizygotic pairs, the right-handed twins died first. In 50% of
      monozygotic pairs, right-handed twins died first. The prevalence of not being
      right-handed was higher among males (9.2%) than females (6.5%); there was a
      similar frequency of non-right-handedness in monozygotic (8.0%) and dizygotic
      (7.8%) twins. We did not find evidence of excess mortality among non-right-handed
      adult twins in this follow-up study.

PMID- 10955412
TI  - Reliability of proxy-reported and self-reported household appliance use.
AB  - Exposure assessment presents a major challenge for studies evaluating the
      association between household exposure to electric and magnetic fields and
      adverse health outcomes, especially the reliance on proxy respondents when study
      subjects themselves have died. We evaluated the reliability of proxy- and self
      reported household appliance exposure. We recruited 92 healthy couples through
      either random-digit dialing or newspaper advertisements. Trained interviewers
      administered questionnaires to each member of a couple independently to assess
      the reliability of proxy-reported household appliance use. Eighty-five couples
      completed a second interview 2 months later to assess the reliability of self
      reported appliance use. Reliability of proxy-reported appliance exposure was good
      when we inquired about having any exposure to each of the eight indicator
      appliances during the past year (range of kappa coefficients = 0.63-0.85; median
      = 0.76) but was lower with increased time to recall or increased detail.
      Reliability of self respondents reporting 2 months apart was excellent (range of
      kappa coefficients = 0.75-0.94; median = 0.87) for having any exposure to the
      eight indicator appliances during the past year, but reliability was again lower
      with increased detail. When we used self reports at the first interview as the
      standard, little systematic over- or underreporting occurred for proxy
      respondents or for self respondents reporting 2 months later. Because this study
      did not include cases of specific disease, these findings of no systematic
      differences in reporting do not refer to case or control status. In summary,
      reliability of self respondents' reports of appliance use is very good for recent
      time periods and good for broad aspects of exposure in distant time periods.
      Proxy respondents can provide information regarding broad aspects of appliance
      exposure in the past year, but detailed aspects of exposure or exposure in more
      distant time periods is not reliable.

PMID- 10955413
TI  - Intrauterine devices and pelvic inflammatory disease: meta-analyses of published
      studies, 1974-1990.
AB  - We conducted a meta-analysis of 36 papers published between 1974 and 1990 to
      estimate the effects of intrauterine device (IUD) use and Dalkon Shield use, in
      particular, on pelvic inflammatory disease (PID). The number of women studied in
      each report ranged from 50 to 26,507. For general IUD use, analyses were
      separated by type of PID (symptomatic or asymptomatic) because of extreme rate
      ratio heterogeneity across studies. Dalkon Shield rate ratios were more
      homogeneous and were considered in a single meta-regression. There was
      substantial heterogeneity, however, in all three meta-regressions; the rate-ratio
      estimates ranged from 0.51 to 12 for IUD use and symptomatic PID, from 1.0 to 132
      for IUD use and asymptomatic PID, and from 0.32 to 28 for Dalkon-Shield use and
      PID. This heterogeneity appeared to be due to differences in reference groups,
      study populations, and characteristics of study design. We observed consistent,
      positive associations of IUD use with both symptomatic and asymptomatic PID.
      These associations were largest for the Dalkon Shield.

PMID- 10955414
TI  - Unintentional injury deaths in an adult Finnish population from 1971-1997.
AB  - We investigated the trends in age-standardized rates (per 100,000 persons-years)
      of unintentional injury deaths in adult Finns from 1971-1997. In 1971, the
      leading category of unintentional injury resulting in death among Finnish men was
      road traffic accidents (age-standardized death rate 47 per 100,000 person-years).
      This rate has declined sharply, reaching 13 per 100,000 person-years in 1997.
      Simultaneously, the rate of fall-induced death among men gradually increased from
      17/100,000 person-years in 1971 to 21/100,000 person-years in 1997. In 1997 the
      death rate from falls in men was greater than that of any other category of
      injury. In 1971, traffic caused fewer deaths in women (rate 17/100,000 person
      years) than men, and declined from there to a rate of 6/100,000 person-years in
      1997. Concurrently the rate of fall-induced deaths in women also decreased, from
      27/100,000 person-years in 1971 to 17/100,000 person-years in 1997. Falling,
      however, was the leading cause of injury-related death in 1997. Thus, in the
      period 1971-1997, falls replaced road traffic accidents as the leading cause of
      unintentional injury death in Finland.

PMID- 10955415
TI  - Hormone replacement therapy and the risk of myocardial infarction in women with
      coronary risk factors.
AB  - To assess the risk of myocardial infarction in users of post-menopausal hormone
      replacement therapy who are at high risk of coronary disease because of
      hypertension, diabetes mellitus, or smoking, we used data from a previously
      published case-control study of women 45-74 years. After adjustment for age,
      ethnicity, and education, the odds ratio for myocardial infarction in current
      users of hormone replacement therapy was 0.9 (95% confidence interval (CI) = 0.5
      1.6) in women with no major coronary risk factors, 0.8 (95% CI = 0.5-1.8) in
      women with one risk factor, and 1.1 (95% CI = 0.5-2.2) in women with two risk
      factors.

PMID- 10955416
TI  - A stand-alone windows applications for computing exact person-years, standardized
      mortality ratios and confidence intervals in epidemiological studies.
AB  - We introduce a stand-alone and user-friendly person-years and mortality
      computation program (PAMCOMP) for calculating exact person-years and standardized
      mortality and incidence ratios running under Windows 95/98 and NT. The
      calculation of person-years allows flexible stratification by self-defined and
      unrestricted categories of age and calendar years. Furthermore, it is possible to
      lag person-years to account for latency periods. The standardized mortality ratio
      computation includes calculation of 90%, 95%, and 99% confidence intervals.
      Import and export filters for standard personal computer file formats are
      available. The software is free of charge and can be downloaded from:
      http://medweb.uni-muenster.de/institute/epi/ pamcomp/pamcomp.html

PMID- 10955417
TI  - Workshop on research into the health effects of cellular telephones.

PMID- 10955418
TI  - Recent trends in prostate cancer mortality in the European Union.

PMID- 10955419
TI  - Simpson's paradox in meta-analysis.

PMID- 10955420
TI  - Oral-contraceptive use, anovulatory action, and risk of epithelial ovarian
      cancer.

PMID- 10955421
TI  - Should women with a family history of breast cancer avoid use of oral
      contraceptives?

PMID- 10955422
TI  - Is ovarian hyperstimulation syndrome associated with a poor obstetric outcome?

PMID- 10955423
TI  - Maternal height and external pelvimetry to predict cephalopelvic disproportion in
      nulliparous African women: a cohort study.
AB  - OBJECTIVE: To assess external pelvimetry and maternal height, as predictors of
      cephalopelvic disproportion. DESIGN: Prospective cohort study. SETTING: Four
      hospitals in Zaire. POPULATION: Six hundred and five nulliparous women. METHODS:
      Maternal height and external pelvimetry were assessed during the third trimester
      antenatal visit. Cut off values for considering women at risk for cephalopelvic
      disproportion were height < 150 cm and external pelvic distances < 10th centile
      for the population. Logistic regression analysis, combining height and pelvic
      measurements, was performed to predict women at risk for cephalopelvic
      disproportion. MAIN OUTCOME MEASURE: Cephalopelvic disproportion was considered
      when there was caesarean section for failure to progress, vacuum or forceps
      delivery or intrapartum stillbirth. RESULTS: Cephalopelvic disproportion was
      present in 42 women. In univariate analysis, height, intertrochanteric diameter
      and the transverse diagonal of Michaelis sacral rhomboid area were found to be
      associated with cephalopelvic disproportion. Logistic regression analysis showed
      that maternal height < 150 cm and/or transverse diagonal < 9.5 cm were the
      variables most associated with cephalopelvic disproportion. The adjusted odds
      ratios were 2 x 2 (95% CI 0.9 to 5.4) and 6.5 (95% CI 3.2 to 13.2), respectively.
      The positive predictive value and likelihood ratio were 24% and 4.0 (95% CI 2.8
      to 5.8), respectively. The addition of transverse diagonal to maternal height
      increased the sensitivity in predicting cephalopelvic disproportion from 21% to
      52%. CONCLUSION: In addition to height, transverse diagonal measurement is able
      to predict one out of two cases of cephalopelvic disproportion in nulliparous
      women. After validation in a separate cohort, this simple predictive method may
      be used in peripheral centres for timely referral of pregnant women at risk for
      cephalopelvic disproportion.

PMID- 10955424
TI  - Mitral stenosis in pregnancy: a four-year experience at King Edward VIII
      Hospital, Durban, South Africa.
AB  - OBJECTIVE: To evaluate prospectively mitral stenosis in pregnancy with emphasis
      on women with persistent symptoms. SETTING: King Edward VIII Hospital, a tertiary
      referral obstetric unit. PARTICIPANTS: One hundred and twenty-eight consecutive
      women with mitral stenosis. DEMOGRAPHICS: The mean age was 27 years and 38 women
      (30%) were primigravidae. Seventy-eight (61%) women had their first cardiac
      evaluation in the third trimester. Fifty-four women (42%) of these women had
      mitral stenosis diagnosed for the first time in the index pregnancy. Twenty-nine
      (23%) had a previous mitral valvulotomy. Nineteen women (15%) developed
      hypertension during pregnancy, 10 of whom had pre-eclampsia. Sixty-three women
      (49%) had a mitral valve area of < or = 1.2 cm2 with 11 having critical mitral
      stenosis (mitral valve area < or = 0.8 cm2). Atrial fibrillation was present in
      12 women. Most women (87%) required medical therapy to control the heart rate.
      OUTCOME IN PERSISTENT SYMPTOMATIC WOMEN: Intervention was considered in 37 women
      (29%) who remained symptomatic, 11 (9%) of whom had a calcified mitral valve. The
      remaining 26 women were scheduled for balloon mitral valvulotomy during
      pregnancy, 20 of whom had balloon mitral valvulotomy with good effect (16
      antepartum; 4 postpartum). In seven women, scheduled balloon mitral valvulotomy
      was not performed because of advanced preterm labour (n = 5), fetal distress (n =
      1) and preterm labour with fetal distress (n = 1). These seven, together with the
      11 with calcific mitral stenosis, were managed conservatively with good outcome.
      MATERNAL COMPLICATIONS: Fifty-one percent had maternal complications, the
      majority occurring at their initial admission to hospital. Pulmonary oedema was
      the most frequent. Multiple logistic regression analysis showed that the severity
      of stenosis assessed by measurement of the mitral valve area by echo-Doppler was
      the most powerful predictor of maternal pulmonary oedema. The other factors were
      late antenatal presentation, presence of symptoms prior to the index pregnancy
      and diagnosis of cardiac disease for the first time in the index pregnancy.
      CONCLUSION: Despite serious disease, women with persistent symptoms treated
      either by balloon mitral valvulotomy where feasible, or conservatively with close
      noninvasive monitoring, had a satisfactory fetal and maternal outcome.

PMID- 10955425
TI  - A randomised controlled pilot study of the management of gestational impaired
      glucose tolerance.
AB  - OBJECTIVE: To determine whether a study of a less intensive form of management
      for impaired glucose tolerance in pregnancy is feasible and whether women would
      accept randomisation. DESIGN: Prospective randomised controlled study. SETTING: A
      large district general hospital and a large teaching hospital in West Yorkshire.
      SAMPLE: Seventy women with impaired glucose tolerance in pregnancy. METHODS: One
      group monitored plasma glucose up to four times daily. The other group did not
      monitor plasma glucose at all. MAIN OUTCOME MEASURES: The number of women
      recruited of those approached and neonatal admissions to special care baby units
      in each group. RESULTS: Sixty-eight of 70 women approached entered the study.
      There were no statistically significant differences between the groups in
      neonatal outcome measures. The median number of plasma glucose measurements in
      the monitored group was 118 (range 0-500), and 19% of women in the monitored
      group were treated with insulin. CONCLUSIONS: This study fails to demonstrate any
      benefit from intensive management of impaired glucose tolerance in pregnancy with
      additional maternal inconvenience. This pilot study has shown that a large
      randomised controlled study of the management of impaired glucose tolerance in
      pregnancy is not only feasible but necessary.

PMID- 10955426
TI  - Sexuality and sexual activity in pregnancy.
AB  - OBJECTIVES: To evaluate women's sexual experience in pregnancy, and to describe
      their sources of information regarding sexuality during this period. DESIGN:
      Cross-sectional study. SETTING: The offices of obstetricians providing obstetric
      care in a tertiary care university hospital in St. John's, Newfoundland, Canada.
      POPULATION: One hundred and forty-one pregnant women. METHODS: Pregnant women
      anonymously completed self-administered questionnaires regarding sexuality and
      sexual activity during pregnancy. Responses were summarised using descriptive
      statistics, and comparisons were made between the trimesters of pregnancy.
      Multiple logistic regression was performed to assess the influences of a variety
      of factors on sexual activity. RESULTS: Vaginal intercourse and sexual activity
      overall decreased throughout pregnancy (P = 0.004 and 0.05, respectively) with
      the trimester of pregnancy being the only independent predictor. Most women
      reported a decrease in sexual desire (58%). Overall, 49% of women worried that
      sexual intercourse may harm the pregnancy. Concerns regarding sexual activity
      leading to preterm labour or premature rupture of membranes increased as the
      pregnancy progressed (P < 0-001 and P = 0-001, respectively). Only 29% of women
      discussed sexual activity in pregnancy with their doctor and 49% of these women
      raised the issue first, with 34% feeling uncomfortable in bringing up the topic
      themselves. Most women (76%) who had not discussed these issues with their doctor
      felt they should be discussed. CONCLUSIONS: A reduction in sexual activity,
      vaginal intercourse and sexual desire occurs in many women as pregnancy
      progresses. Both the woman and her partner have concerns regarding complications
      in the pregnancy as a result of sexual intercourse. The majority of women wish to
      discuss these issues with their doctor, but are not always comfortable raising
      the topic themselves.

PMID- 10955427
TI  - Pregnancy outcome in carriers of fragile X.
AB  - OBJECTIVE: To evaluate pregnancy outcome in women who are carriers of fragile X.
      DESIGN: Cross-sectional case-control study. SETTING: Department of Obstetrics and
      Gynaecology, Kuopio University Hospital, Finland. SAMPLE: Sixty-three singleton
      pregnancies in carriers of fragile X who were referred for genetic counselling
      and prenatal diagnosis to Kuopio University Hospital. METHODS: Logistic
      regression analysis was used to compare pregnancy outcome in women who are
      fragile X carrier with outcome of the general obstetric population. RESULTS:
      Carriers of fragile X often experienced more bleeding in late pregnancy than did
      the reference group. Otherwise, the course and outcome of pregnancy were
      comparable in both groups. CONCLUSION: Pregnancy outcome in women who are
      carriers of fragile X is favourable. There is no need to initiate special fetal
      monitoring because of the fragile X status of the woman.

PMID- 10955428
TI  - Determinants of umbilical cord arterial 8-iso-prostaglandin F2alpha
      concentrations.
AB  - OBJECTIVE: To determine the concentration of 8-isoPGF(2alpha) in cord blood as a
      measure of oxidative stress during labour, and to compare them with other
      established parameters of in vivo lipid peroxidation and with the acid-base
      status of the newborn. METHOD: Umbilical cord arterial and venous blood samples
      were collected from 81 singleton term deliveries for determination of 8
      isoPGF(2alpha), malondialdehyde and organic hydroperoxides. In addition,
      metabolites derived from the oxidative metabolism of purines during hypoxia
      reoxygenation and routine cord blood of oxygen saturation, pH, pO2, pCO2, HCO3
      and base excess were measured. RESULTS: Arterial concentrations of 8
      isoPGF(2alpha) were significantly higher in cases with fetal distress, tight
      nuchal cord (P < 0.001), the umbilical coiling index, and male sex (P < 0.05) (R2
      = 0.48). No correlation was found with any parameter of acid-base status. In
      arterial and venous blood the concentrations of organic hydroperoxides and
      hypoxanthine significantly correlated with the fetal nuchal cord (P < 0.001) (R2
      = 0.26 and 0.16, respectively). CONCLUSION: Our findings indicate that 8
      isoPGF2(alpha) in cord arterial blood is a suitable parameter to quantify a
      possible oxidative stress in the fetus during labour. Measurements of the F2
      isoprostane concentrations in cord blood at labour provide a clinically useful
      method to assess the perinatal outcome.

PMID- 10955430
TI  - Cord blood oxygen saturation in vigorous infants at birth: what is normal?
AB  - OBJECTIVE: To define the normal ranges of umbilical cord blood oxygen saturation
      (SaO2) and acid-base status at birth and to evaluate the effect of gestational
      age on cord blood values in vigorous newborn infants following spontaneous
      vaginal birth from a vertex position. DESIGN: Prospective study. SETTING:
      Department of Obstetrics and Gynaecology, University of Graz, Austria. SAMPLE:
      Cord blood samples from 1281 vigorous newborn infants. METHODS: Cord blood
      sampling was performed following on newborn infants following spontaneous vaginal
      birth in a vertex position. SaO2 was measured directly by a spectrophotometer and
      pH, base excess, pCO2 and pO2 by a pH/blood-gas analyser. Infants with a 5-minute
      Apgar score > or = 7 were considered vigorous. Subgroups were classified
      according to the gestational age: preterm, term and post-term (< 37, 37-42 and >
      42 weeks, respectively). RESULTS: The median umbilical artery SaO2 was 24.3% and
      the 2.5th centile was as low as 2.7%. The median umbilical artery values were pH
      = 7.25, base excess = -4.3 mmol/L and pO2 = 16 mmHg. The 2.5th centiles were
      7.08, -11.1 mmol/L and 5 mmHg, respectively. The median umbilical artery pCO2 was
      50 mmHg and the 97.5th centile was 75 mmHg. The mean umbilical artery and vein
      SaO2 values were not significantly influenced by gestational age. The umbilical
      artery SaO2 and base excess values were strongly skewed. The mean umbilical
      artery pH values in preterm infants were higher than in other subgroups. The mean
      umbilical artery and vein base excess values were lower in post-term newborn
      infants than in other subgroups. CONCLUSIONS: The physiological range of oxygen
      saturation in umbilical cord of vigorous newborn infants at birth is wide and
      skewed. In contrast to pH and base excess, umbilical cord blood oxygen saturation
      is not influenced significantly by gestational age at birth.

PMID- 10955429
TI  - Lipid peroxidation in umbilical arterial blood at birth: the effects of breech
      delivery.
AB  - OBJECTIVE: To determine oxygen free radical activity in breech presentation at
      birth and relate it to umbilical cord blood acid-base status. DESIGN: A series of
      63 singleton deliveries (28 cephalic deliveries as controls), 23 breech
      deliveries with normoacidemia, and 12 breech deliveries with mild acidaemia) had
      determination of malondialdehyde and acid-base parameters. SETTING: The delivery
      suite in the Department of Obstetrics and Gynaecology at the Suleyman Demirel
      University, Isparta, Turkey. PARTICIPANTS: Sixty-three singleton infants born at
      term with spontaneous or induced labour and initially normal fetal heart rate
      tracing. METHODS: After delivery, umbilical cord arterial and venous blood
      samples were collected for the determination of malondialdehyde concentrations.
      Oxygen saturation, pO2, pCO2, pH, and base excess were also measured. MAIN
      OUTCOME MEASURES: Umbilical cord arterial and venous blood gases and
      malondialdehyde levels. RESULTS: There was a significant correlation between
      umbilical arterial and venous levels of malondialdehyde and all acid-base
      parameters (P < 0.001). There were negative correlations between malondialdehyde
      levels and pH, pO2 and bicarbonate, while there was a positive correlation
      between malondialdehyde concentrations and pCO2. A positive correlation between
      malondialdehyde levels and base excess was present in the control group and total
      breech group (n = 35). The malondialdehyde levels in the total breech group,
      nonacidaemic breech group (n = 23) and the mildly acidaemic breech group (n = 12)
      were significantly higher than those in the control group (P < 0.0001). However,
      acid-base parameters in the nonacidaemic breech group were not statistically
      different from those in the control group. CONCLUSION: Lipid peroxidation
      products (malondialdehyde) existed to some extent in the umbilical cords of
      newborns with normal acid-base parameters in breech delivery. Our data support
      the contention that lipid peroxide may be a more sensitive measure for metabolic
      dysfunctions due to fetal hypoxia than acid-base balance.

PMID- 10955431
TI  - Maternal serum total activin A and follistatin in pregnancy and parturition.
AB  - OBJECTIVE: To examine changes in maternal serum levels of activin A and
      follistatin during pregnancy and labour. DESIGN: In three cross sectional and
      three longitudinal studies venous blood was collected from women during
      pregnancy, spontaneous labour, labour induction and prior to elective caesarean
      section for the measurement of activin A and follistatin. SETTING: Monash Medical
      Centre, Clayton, Victoria, Australia. POPULATION: One hundred and twenty-three
      women participated in a cross sectional study in pregnancy, 18 women in two
      longitudinal pregnancy studies, 36 women in a cross sectional labour study, nine
      women in a longitudinal study of labour induction. Ten women undergoing elective
      caesarean section were also studied. METHODS: Activin A and follistatin were
      measured using two sensitive and specific enzyme-linked immunosorbent assays.
      RESULTS: In the cross sectional study of pregnancy, mean (SEM) maternal serum
      activin A and follistatin levels increased towards term (2.4 ng/mL (0.3) and 1.8
      ng/mL (0.3) in first trimester to 18.9 ng/mL (3.8) and 5.3 ng/mL (0.9) at term,
      respectively), but the longitudinal study revealed that levels plateau in the
      last three weeks of pregnancy (16.0 ng/mL (2.6) and 6.2 ng/mL (1.4) at 37 weeks
      and 16.6 ng/mL (3.5) and 6.2 ng/mL (0.5) before labour for activin A and
      follistatin, respectively). There was no difference in levels of activin A and
      follistatin between women delivered by caesarean section and labouring women at
      term (14.9 ng/mL (2.8) vs 11.0 ng/mL (0.93) and 5.95 ng/mL (0.67) vs 5.71 ng/mL
      (0.63), respectively) and levels of both proteins did not alter throughout
      spontaneous or induced labour. CONCLUSIONS: We believe that these data argue
      against activin A playing an acute role in the initiation or regulation of human
      parturition.

PMID- 10955432
TI  - Factors affecting fetal weight distribution in women with type I diabetes.
AB  - OBJECTIVE: To identify factors independently affecting fetal weight in women with
      type I diabetes. DESIGN: Prospectively recorded data in consecutive women with
      type I diabetes, between 1975-1992. SETTING: Simpson Memorial Maternity Hospital,
      Edinburgh. Population Three hundred and two pregnancies with type I diabetes
      identified before pregnancy, with antenatal care and delivery in the Simpson
      Memorial Maternity Hospital, a singleton pregnancy, and the same diabetic
      physician. METHODS: Normal ranges for birthweight were established for the total
      hospital population. All cases and the total population had pregnancy dating by
      ultrasound. The relation between standardised birthweight and explanatory
      variables was investigated using correlation analysis, t tests and chi2 tests as
      appropriate, and subsequently using multiple linear regression. RESULTS:
      Standardised birthweight in cases, compared with the reference population, showed
      a unimodal, approximately normal distribution, markedly shifted to the right
      (mean + 1.26 SD). The most predictive variable was glycated haemoglobin
      concentration at 27-33 weeks, which explained 6.3% of the birthweight variance,
      while smoking explained 2.7% and maternal weight 2.0%. There was a trend towards
      a negative relationship with glycated haemoglobin concentration at 6-12 weeks.
      Smoking and glycated haemoglobin concentration were strongly intercorrelated.
      CONCLUSIONS: Most of the variance in standardised birthweight remains
      unexplained, but glycated haemoglobin concentration at 27-33 weeks is the most
      powerful explanatory variable. Possible reasons why there is not a stronger
      relationship between markers of maternal glycaemia and birthweight are discussed.

PMID- 10955433
TI  - Comparative assessment of pelvic floor strength using a perineometer and digital
      examination.
AB  - OBJECTIVE: To determine whether digital assessment of pelvic floor contraction
      strength is as reliable as vaginal perineometry and to assess the practice of
      pelvic floor exercises by women. DESIGN: A blinded, two-assessor protocol,
      prospectively testing a volunteer sample of women. POPULATION: Two hundred and
      sixty-three women (from a total of 278), aged 16-75 years, attending a general
      gynaecological clinic with nonurinary symptoms. METHODS: Participants answered a
      questionnaire regarding urinary symptoms and practice of pelvic floor exercises.
      History and examination was carried out by the clinician, and pelvic floor
      strength scored digitally using the Oxford Scale. Pelvic floor strength was then
      assessed by the physiotherapist, using a PFX perineometer. The physiotherapist
      was blinded to the woman's history, examination findings and digital assessment
      score. Both the clinician and physiotherapist were blinded to the questionnaire
      responses. MAIN OUTCOME MEASURES: Digital pelvic floor contraction assessment,
      according to the Oxford Scale, was compared with perineometric assessment as the
      gold standard - examined against the background of the questionnaire findings.
      RESULTS: Of 263 patients, 53 were nulliparous (20%), and 210 parous (80%). Only
      49 women carried out regular pelvic floor exercises (19%), and all were parous
      and admitted to troublesome urinary symptoms. Stress urinary incontinence was
      reported by 28% of all women (38.1% of parous women and 10.5% of nulliparous
      women). For both methods, there was no difference in the range of results when
      parity was taken into account. Concordance studies showed good agreement between
      digital and perineometric assessment of pelvic floor strength. The kappa value of
      0.73 (95% confidence interval 0.67-0.79) indicated substantial agreement between
      the two methods. CONCLUSION: There is good agreement between digital assessment
      of pelvic floor contraction strength and vaginal perineometry. Assessment during
      gynaecological examination may help to identify women with fascial defects of the
      pelvic floor, as well as those at risk of genital prolapse or urinary symptoms.

PMID- 10955434
TI  - A comparison of 25 mg and 50 mg oestradiol implants in the control of climacteric
      symptoms following hysterectomy and bilateral salpingo-oophorectomy.
AB  - OBJECTIVES: 1. To compare the effects of 25 mg and 50 mg oestradiol implants on
      serum follicle stimulating hormone and oestradiol levels; and 2. to assess the
      relationship of the dose of oestradiol implant and serum oestradiol on the
      effectiveness and duration of climacteric symptom control. DESIGN: Randomised,
      double-blind investigation. PARTICIPANTS: Forty-four women, who had undergone
      total abdominal hysterectomy and bilateral salpingo-oophorectomy. METHODS: The
      women were randomised to receive either 25 mg (n = 20) or 50 mg (n = 24)
      oestradiol implants. Follow up consisted of prospective symptom enquiry and
      hormone assays. MAIN OUTCOME MEASURES: Primary: climacteric symptom control:
      duration and effectiveness; secondary: serum oestradiol and follicle stimulating
      hormone levels. RESULTS: Serum oestradiol was significantly higher and serum
      follicle stimulating hormone significantly lower after the fourth month of
      treatment in women receiving 50 mg implants. No significant difference in symptom
      control was noted in the two groups. The mean duration of symptom control was
      similar in the two groups: 5.9 months (SD 2.4) in those receiving 50 mg
      oestradiol and 5.6 months (SD 2.3) in those receiving 25 mg. CONCLUSION: The
      higher level, 50 mg oestradiol implants does not result in better control of
      symptoms nor in longer periods of symptom control compared with 25 mg oestradiol
      implants. In order to maximise compliance, 25 mg oestradiol implants should
      therefore be the treatment of choice for women with normal bone density seeking
      relief of climacteric symptoms.

PMID- 10955435
TI  - Postmenopausal hormone replacement improves proteinuria and impaired creatinine
      clearance in type 2 diabetes mellitus and hypertension.
AB  - OBJECTIVE: To determine whether hormone replacement therapy can reverse
      established renal microvascular damage in type 2 diabetes and hypertension.
      DESIGN: Prospective, single centre clinical trial. SETTING: Outpatient clinics.
      PARTICIPANTS: Sixteen diabetic and hypertensive postmenopausal women (age 47-57
      years) METHODS: Administration of a cyclic combination of oestradiol and
      norgestrel orally for 3.5 monthly cycles. RESULTS: Comparing the baseline values,
      mean (SD) 24-hour urine protein excretion was reduced from 0.452 g (0039) to
      0.370 g (0.047) (P < 0.01) and creatinine clearance was increased from 1.68
      mL/sec (0.11) to 1.77 mL/sec (0.08) (P < 0.05). Fasting plasma glucose also
      improved from 6.92 mmol/L (0.47) to 6.51 mmol/L (0.28) (P < 0.05), as did serum
      total cholesterol from 7.26 mmol/L (0.28) to 6.65 mmol/L (0.14) (P < 0.05). Blood
      pressure did not change significantly. Univariate linear regression analysis
      showed no significant correlation between the individual changes in blood
      pressure, fasting plasma glucose or serum cholesterol and the individual changes
      in proteinuria or creatinine clearance. CONCLUSIONS: This study shows that
      hormone replacement therapy may reduce proteinuria, and even improve creatinine
      clearance, in diabetic and hypertensive postmenopausal women. These effects are
      additive to nephroprotective therapy, and the mechanisms appear unrelated to
      conventional risk factors for vascular complications, such as high blood
      pressure, elevated plasma glucose or serum cholesterol.

PMID- 10955437
TI  - Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the
      treatment of bothersome lower urinary tract symptoms.
AB  - OBJECTIVES: To assess the efficacy of an oestradiol-releasing vaginal ring and
      oestriol pessaries in the alleviation of lower urinary tract symptoms occurring
      after the menopause. DESIGN: Randomised, parallel group, controlled trial.
      SETTING: Twenty-six clinics of practising gynaecologists and one outpatient
      clinic at a department of obstetrics and gynaecology. POPULATION: Two hundred and
      fifty-one postmenopausal women, with a mean age of 66 years, reporting at least
      one bothersome lower urinary tract symptom. METHODS: One hundred and thirty-four
      women were treated with the oestradiol-releasing ring for 24 weeks; 117 women
      were treated with oestriol pessaries 0.5 mg every second day for 24 weeks. MAIN
      OUTCOME MEASURES: Subjective scores of urgency, frequency, nocturia, dysuria,
      stress incontinence and urge incontinence. RESULTS: The two treatments were
      equally efficacious in alleviating urinary urgency (51% vs 56%), urge
      incontinence (58% vs 58%), stress incontinence (53% vs 59%) and nocturia (51% vs
      54%). Dysuria was alleviated in 76% vs 67%, equivalence was not demonstrated. No
      statistically significant difference was found for any primary efficacy endpoint.
      Sixty percent of the participants rated the form of administration via the
      vaginal ring as excellent, compared with 14% for the pessaries (P < 0.0001).
      CONCLUSIONS: Low dose vaginally administered oestradiol and oestriol are equally
      efficacious in alleviating lower urinary tract symptoms which appear after the
      menopause. The form of administration of the vaginal ring, seems to be more
      acceptable than oestriol pessaries.

PMID- 10955436
TI  - Effect of postpartum pelvic floor muscle training in prevention and treatment of
      urinary incontinence: a one-year follow up.
AB  - OBJECTIVE: To evaluate the long term effect of a postpartum pelvic floor muscle
      training course in prevention and treatment of urinary incontinence. DESIGN: A
      prospective matched controlled trial. SAMPLE AND METHODS: All women who had
      participated in a matched controlled study evaluating the effect of an eight-week
      pelvic floor muscle training program in prevention and treatment of urinary
      incontinence in the immediate postpartum period were contacted by telephone one
      year after delivery. They were invited to participate in a follow up study. The
      study group consisted of 81 matched pairs (n = 162), with a mean age (range) 28
      years (19-40), and mean number (range) of deliveries 1.8 (1-5). Seventy-six pairs
      had normal vaginal deliveries and five elective caesarean sections. Registration
      of continence status was by structured interview and a standardised pad test.
      Clinical assessment of pelvic floor muscle function and strength were by vaginal
      palpation and vaginal squeeze pressure. MAIN OUTCOME MEASURE: Stress urinary
      incontinence. RESULTS: At the one year follow up, significantly more women in the
      former control group than in the training group reported stress urinary
      incontinence and/or showed urinary leakage at the pad test (P < 0.01). A
      significantly greater (P < 0.01) muscle strength increase in the period between
      16th week and one year postpartum was demonstrated in the former training group
      (mean 4.4 cm H2O, 95% CI 3.2-5.6) than in the control group (mean 1.7 cm H2O, 95%
      CI 0.8-2.7). CONCLUSION: This one year follow up study demonstrates that a
      specially designed postpartum pelvic floor muscle training course was effective
      in the prevention and treatment of stress urinary incontinence. The benefits from
      pelvic floor muscle training are still present one year after delivery.

PMID- 10955439
TI  - An in vivo comparative study of the pregnant and nonpregnant cervix using
      electrical impedance measurements.
AB  - Electrical impedance may be measured using electrodes on the surface of the
      cervix and recording the potential that results when an electrical current is
      passed. Increased hydration of the cervix has been described throughout pregnancy
      and occurs most dramatically before labour. This study compared tissue impedance
      measurements of the pregnant and non-pregnant cervix and found a statistically
      significant lower value (P < 0.001) in pregnancy. Further work may show that such
      measurements alter in relation to labour onset.

PMID- 10955438
TI  - A multicentre evaluation of a new surgical technique for urethral bulking in the
      treatment of genuine stress incontinence.
AB  - This prospective study assesses the surgeon and patient acceptability of a new
      implantation device for transurethral Macroplastique injection, as well as the
      safety and effectiveness of the technique. Ten women with genuine stress
      incontinence were recruited at each of four participating urogynaecological
      centres. Treatment was performed in an outpatient or day case setting and follow
      up took place at six weeks and three months after treatment. Those in whom
      treatment had failed were offered re-treatment. The operator acceptance of the
      device was rated as excellent or acceptable in 95% after the first treatment and
      100% after re-treatment. Urethral insertions were rated acceptable in 92.5%. Pain
      was scored as mild to moderate in 89% of all insertions. The overall success rate
      was 74.3% at three months with an implantation rate of 1.35 which appears to be
      comparable to published endoscopic data. We have concluded from this study that
      the Macroplastique implantation device is safe to use and provides simplified,
      yet effective alternative to the endoscopic implantation of urethral bulking
      agents.

PMID- 10955440
TI  - Tissue expansion vaginoplasty: modified reconstruction following extrusion of the
      expander.

PMID- 10955441
TI  - Isolated torsion and haemorrhagic infarction of a normal fallopian tube in an
      eleven year old girl.

PMID- 10955442
TI  - Prenatal diagnosis and successful preterm delivery of a fetus with long QT
      syndrome.

PMID- 10955443
TI  - Thrombocytopenia and leucopenia precipitated by pregnancy in a woman with
      myasthenia gravis.

PMID- 10955444
TI  - Sonographic diagnosis of funic presentation: implications for delivery.

PMID- 10955445
TI  - Planned vaginal delivery versus elective caesarean section: a study of 705
      singleton term breech presentations.

PMID- 10955446
TI  - A randomised controlled trial comparing transvaginal ultrasound, outpatient
      hysteroscopy and endometrial biopsy with inpatient hysteroscopy and curettage.

PMID- 10955447
TI  - Guidelines for the management of ovarian cancer.

PMID- 10955448
TI  - Randomised comparison of Burch colposuspension versus anterior colporrhaphy in
      women with stress urinary incontinence and anterior vaginal wall prolapse.

PMID- 10955449
TI  - Immunohistochemistry on cell blocks from fine-needle cytopunctures of primary
      breast carcinomas and lymph node metastases.
AB  - We assessed the reliability of prognostic biologic markers by means of
      immunohistochemistry on cell blocks obtained from diagnostic fine-needle
      cytopunctures of breast carcinomas and their lymph node metastases.
      Immunohistochemical studies of MIB-1 (Ki-67), estrogen receptors (ER),
      progesterone receptors (PR), p53, and c-erb-B-2 were performed in 55 cases of
      primary breast carcinoma on cell blocks (cytoblock technique) and on their
      corresponding tissue samples (46 mastectomy specimens and 9 Trucut biopsies) and
      in 38 cases on cell blocks from fine-needle cytopunctures of both the primary
      breast tumors and their concurrent lymph node metastases. Interobserver
      reproducibility ranged from 87 to 100%, depending on the marker. A good
      correlation was observed between immunostaining assessment on cell blocks and on
      the corresponding tumor tissues as follows: Ki-67 (85%), ER (96%), PR (82%), p53
      (76%), and c-erb-B-2 (84%). An excellent correlation was observed between cell
      block results for primary tumors and node metastases; however, a far higher
      percentage of Ki-67-positive nuclei was observed in the nodes than in the
      corresponding tumors in seven cases. All nodes corresponding to ER- or PR
      negative tumors were also negative, whereas the nodes corresponding to two ER
      positive and one PR-positive tumor were negative. Marked discrepancies were also
      noted with p53 in two cases and with c-erb-B-2 in two cases. Most discrepancies
      occurred with Trucut biopsies and with breast tumors that contained a large
      intraductal component. We conclude that cell blocks prepared from fine-needle
      cytopuncture specimens of breast carcinomas and their node metastases are useful
      when planning neoadjuvant treatment.

PMID- 10955450
TI  - Intrarenal schwannoma: a report of four cases including three cellular variants.
AB  - Renal schwannomas are extraordinarily rare neoplasms; only six have been
      reported, the majority of which occurred in the renal pelvis. We report the
      clinical and pathologic features of four additional cases. The resected kidney in
      all patients contained a well-demarcated, yellow-tan, smooth, and bulging
      intraparenchymal tumor (mean size, 9.7 cm; range, 4 to 16 cm). Microscopically,
      three cases were classified as cellular schwannomas, and one was a usual-type
      schwannoma, with degenerative nuclear atypia. By immunohistochemistry, all tumors
      were strongly S-100 protein positive and negative for pan-cytokeratin, CD57,
      smooth muscle actin, desmin, and CD34. Epithelial elements were not noted in the
      tumors, and there was no history of any clinical syndromes in these patients.
      Analysis of the four cases showed the mean age at presentation to be 47 years
      (range, 18 to 84 years), with no sex predisposition (two men, two women). Most
      patients were asymptomatic, and all received a diagnosis of renal cell carcinoma
      and treated as having such. Recognition and awareness of these rare, benign
      tumors will assist in the differential diagnosis of spindle cell tumors of the
      kidney and prevent their misdiagnosis as sarcomatoid carcinomas of the kidney or
      renal sarcomas. Our study, the largest series to date of renal schwannomas,
      demonstrates a predilection for the cellular variant in the kidney, documents
      that these tumors may present in the nonhilar region of the kidney, and provides
      clinical evidence of their benign biologic behavior.

PMID- 10955451
TI  - Benign atypical junctional melanocytic hyperplasia associated with intradermal
      nevi: a common finding that may be confused with melanoma in situ.
AB  - Over the past few years, consultation cases thought to represent melanoma in situ
      have been received that consisted of otherwise normal intradermal nevi with an
      abnormal but benign junctional proliferation of melanocytes that we have termed
      benign atypical junctional melanocytic hyperplasia. In order to evaluate the
      incidence of this feature, 400 cases of intradermal nevi were reviewed. Of these,
      25 (6.2%) qualified for inclusion, making this a rather common phenomenon.
      Clinically, patient ages ranged from 18 to 64 years (mean, 35 years), with a male
      to female ratio of 1:1. Face (40%) and back (32%) were the most common locations.
      Histologically, the lesions were predominantly dome-shaped with an intradermal
      component consisting of conventional nevus cells. Most importantly, each lesion
      exhibited prominent individual nevomelanocytic cells dispersed at uneven
      intervals along the dermoepidermal junction in insufficient numbers to be
      considered compound nevi. The cells exhibited abundant pale to clear cytoplasm,
      an increased nuclear:cytoplasmic ratio, and often exhibited prominent nucleoli.
      However, these lesions could be distinguished from melanoma in situ by the lack
      of several features including lateral spread, upward epidermal migration, marked
      cytologic atypia, finely granular "smoky" melanin pigment, mitotic figures, and a
      subjacent host inflammatory response. All cases behaved in a benign fashion.
      Although benign atypical junctional melanocytic hyperplasia is a relatively
      common histological curiosity, it is a potential pitfall in the diagnosis of
      pigmented lesions.

PMID- 10955452
TI  - Encapsulated follicular variant of papillary thyroid carcinoma with bone
      metastases.
AB  - Although true follicular thyroid carcinoma is known to metastasize via the
      bloodstream and give rise to bone and lung metastases, such a pattern of spread
      is rare in papillary thyroid carcinoma. The follicular variant of papillary
      thyroid carcinoma (FVPTC) is believed to behave in a clinical manner similar to
      usual or classical papillary cancer and to follow a similar indolent course.
      There have been a few reports of "aggressive" FVPTC wherein follicular patterned
      tumors with nuclear features of papillary carcinoma have metastasized
      hematogenously; these neoplasms have been diffusely invasive or multicentric in
      the thyroid. We report five cases of FVPTC, which were encapsulated and simulated
      grossly and microscopically follicular adenomas. In two of these, the primary was
      discovered after clinical presentation of bone metastases. In three others, bony
      metastases (without other nonosseous metastases) arose 7 to 17 years after
      thyroid lobectomy for lesions initially diagnosed as follicular adenoma In
      retrospect, these three encapsulated lesions had vascular invasion. We wish to
      bring attention to these innocuous-appearing lesions, which, although sharing
      nuclear features of papillary cancer, behave clinically in an unexpectedly
      malignant fashion.

PMID- 10955453
TI  - HER-2/neu testing in breast carcinoma: a combined immunohistochemical and
      fluorescence in situ hybridization approach.
AB  - We evaluated 750 consecutive invasive breast carcinomas for HER-2/neu utilizing a
      combination of immunohistochemical (IHC) and fluorescence in situ hybridization
      (FISH) methodologies. IHC reactions of 3+ were considered HER-2/neu positive and
      0 and 1+ IHC reactions were considered HER-2/neu negative. IHC reactions of 2+
      were considered inconclusive and reflexed to FISH analysis. In addition, a 10%
      sampling and validation FISH analysis was performed on the positive and negative
      IHC tests. One hundred thirty-eight cases (18.4%) were HER-2/neu positive by IHC
      and/or FISH. One hundred twenty-three of the positive cases (89%) were 3+ IHC
      reactions and 14 positive cases were inconclusive by IHC and amplified by FISH.
      There was concordance with FISH in 77 of 78 (98.7%) of the positive or negative
      IHC cases that were tested (95% confidence interval [CI] = 93.1 to 100%). A
      single IHC-negative case showed HER-2/neu amplification by FISH. Thirty-nine
      cases were 2+ IHC (5.2%); 14 (36%) were amplified, 24 (62%) were not amplified,
      and one was not interpretable. HER-2/neu positivity was observed in 34% of grade
      3 ductal carcinomas, 11.4% of grade 2 ductal carcinomas, 3.2% of grade 1 ductal
      carcinomas, and 3.2% of lobular carcinomas. Occasional cases with discordant IHC
      expression of HER-2/neu within the in situ and invasive carcinoma elements were
      also identified. IHC reliably characterized HER-2/neu in approximately 95% of the
      cases studied (95% CI = 93.0 to 96.2%) and was effective as a primary method for
      evaluating HER-2/neu status. In this study, 2+ IHC reactions were a heterogeneous
      group best regarded as indeterminate or inconclusive; in this series, only 36%
      were amplified by FISH analysis. Our findings suggest that a combination of IHC
      and FISH testing with FISH analysis performed reflexly on all 2+ IHC cases can
      optimize HER-2/neu testing.

PMID- 10955454
TI  - Clear cell carcinoma of the liver: a comparative immunohistochemical study with
      renal clear cell carcinoma.
AB  - Morphologic differentiation of clear cell hepatocellular carcinoma (HCC-CC) from
      clear cell renal carcinoma (RCC-CC) may not be possible without the aid of
      immunohistochemical stains. We performed a battery of immunohistochemical stains
      on 10 previously diagnosed HCC-CCs, and 10 RCC-CCs, in order to determine which
      single or combination of immunostains would be most useful in diagnosis. We
      concluded that a positive Hepatocyte immunostain (DAKO) is sufficient for a
      diagnosis of HCC-CC if enough tissue is available. This immunostain distinguishes
      HCC-CC from other clear cell malignancies with sensitivity of 90% and specificity
      of 100%, when biopsy material is adequate. Other tests were much less sensitive,
      although several had specificity of 100%. A negative immunostain does not exclude
      the diagnosis of HCC-CC (negative predictive value 91%, especially in small
      biopsy material) and should be followed by additional immunostains such as pCEA
      for demonstration of tumor canaliculi, ubiquitin for Mallory bodies, and several
      epithelial cell markers that are typically positive in RCC-CC (epithelial
      membrane antigen, Leu M-1, pancytokeratin) and negative in HCC-CC.

PMID- 10955455
TI  - The role of cell cycle regulatory protein, cyclin D1, in the progression of
      thyroid cancer.
AB  - Cell cycle progression is facilitated by cyclin-dependent kinases that are
      activated by cyclins including cyclin D1 and inactivated by cyclin-dependent
      kinase inhibitors (CDKIs) such as p27. Our previous studies have demonstrated
      decreased p27 expression in both papillary and more aggressive carcinomas of the
      thyroid compared to thyroid adenoma and almost similar level of cyclin D1
      expression between thyroid adenoma and papillary carcinoma. These results
      indicate that CDKIs may have an important role in the carcinogenesis of the
      thyroid and that they probably have a limited role in malignant progression of
      the thyroid cancer. The role of cyclin D1 in malignant progression of thyroid
      carcinoma has yet to be established. We studied the expression of cyclin D1 by
      immunohistochemistry in 34 cases of conventional papillary carcinoma (CPC), 10
      cases of minimally invasive follicular carcinoma (MIFC), and 32 cases of more
      aggressive thyroid carcinoma (ATC), which included 11 tall cell variants, one
      columnar cell variant of papillary carcinoma, seven insular carcinomas, and 13
      anaplastic carcinomas. Cyclin D1 staining was classified by staining score as 0,
      negative; 1+, less than 25%; 2+, 25 to 50%; and 3+, more than 50% tumor cells
      staining positive. Kruskal-Wallis one-way ANOVA and Wilcoxon Rank Sum/Mann
      Whitney U Test was used to assess the difference in the expression of cyclin D1
      between the study groups. Twenty-eight out of the 34 CPCs were cyclin D1
      positive, 24 (70%) were 1+, 3 (9%) were 2+, and one (3%) were 3+ positive. Seven
      of 10 MIFCs were cyclin D1 positive, five (71%) were 1+, and the remaining two
      (29%) were 2+ positive. On the other hand, 28 of 32 ATCs showed cyclin D1
      immunostaining. Of these, three (9%) were 1+, five (13%) were 2+, and 20 (63%)
      were 3+ positive. This study demonstrates a significant overexpression of cyclin
      D1 in ATC compared CPC (P < .001) and MIFC (P < .005), suggesting that the cyclin
      D1 expression may play a role in tumor progression and may have prognostic
      significance in thyroid cancer.

PMID- 10955456
TI  - Therapy-related changes of CD20+ and CD45RO+ lymphocyte subsets in chronic
      myeloid leukemia (CML): an immunohistochemical and morphometric study on
      sequential trephine biopsies of the bone marrow.
AB  - Little information exists about the amount of CD45RO+-T- and CD20+-B-lymphocytes
      in the bone marrow of patients with Philadelphia chromosome-positive chronic
      myelogenous leukemia (Ph1+-CML) at presentation or regarding corresponding
      changes during therapy. On the other hand, quantification of this cell
      compartment seems to be imperative for two reasons: first, the presumed
      association of immunocompetent lymphocyte subsets in the expansion of the
      leukemic cell clone; and second, a speculated relationship with the complex
      generation of myelofibrosis. Therefore, an immunohistological and morphometric
      study was performed on 219 representative trephine biopsies of the bone marrow
      derived from 70 patients with repeated examinations during the course of Ph1+
      CML. For the identification of the different lymphocyte populations, the
      monoclonal antibodies UCHL-1 (CD45RO) and L26 (CD20) were applied on formaldehyde
      fixed and decalcified specimens. In comparison to a control group and calculated
      per hematopoietic cells, the CML bone marrow showed about a 50% decrease in the
      total amount of lymphocytes. Determination of CD45RO+ and CD20+ subsets revealed
      a significant enhancement during treatment. Because of the different intervals
      (range, 10 to 25 mo) between first and last biopsy in the various therapeutic
      groups, results had to be modified by considering dynamic features. This
      calculation included changes of the lymphocyte subpopulations related to time.
      Contrasting the CD45RO+ lymphocytes, a relevant increase in the CD20+ subset
      could be observed after interferon-a treatment or corresponding combination
      regimens. No significant correlations were found between fiber density at onset
      (first biopsy) or development of fibrosis and lymphocyte proliferations in the
      course of CML. Our results are in keeping with the finding that a proper immune
      response consistent with an increased lymphocyte growth seems to be associated
      with a regression of the clonally-transformed cell population. Opposed to a
      repeatedly discussed pathomechanism, we failed to demonstrate any quantitative
      relationships between the extent of lymphocyte proliferations and occurrence or
      progression of myelofibrosis.

PMID- 10955457
TI  - Idiopathic enterocolic lymphocytic phlebitis: a rare cause of ischemic colitis.
AB  - We report on a 74-year-old female patient who was admitted to the hospital
      because of abdominal pain. She underwent a colonoscopy and a stenosing mass was
      found in the cecum. Histologic findings in the biopsy specimens were consistent
      with ischemic colitis. Due to clinical symptoms and the endoscopic and radiologic
      findings that roused the suspicion that the patient was suffering from a
      malignant tumor, a right hemicolectomy was performed. Histology of the resection
      specimen disclosed an inflammation of the veins. It was characterized by a
      predominantly lymphocytic infiltration of the vessels affecting the veins of the
      colonic wall and the mesentery. Furthermore, secondary thrombosis with focal
      venous occlusion was observed. The colon showed extensive ischemic colitis with
      focal transmural coagulation necrosis. The disease was considered to be
      idiopathic lymphocytic phlebitis, which is a rare disease of unknown origin. Our
      patient is well and alive after more than 1 year, supporting the notion that the
      disease shows a benign course after surgery.

PMID- 10955458
TI  - Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical,
      and ploidy analysis of 23 cases.
AB  - Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo
      Clinic between 1968 and 1996, were studied for clinicopathologic features,
      immunohistochemical profile, Ki-67 activity, and ploidy status to identify
      adverse prognostic factors. Females and males were equally affected, and the
      median age at diagnosis was 50 years. The tumors were located mainly in the lower
      extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed
      low cellularity (70%), and eight tumors had high mitotic activity (more than two
      per 10 high-power fields). The tumors were immunoreactive for vimentin (89%),
      synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%).
      Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67
      activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On
      univariate analysis, tumor size > or = 10 cm, high cellularity, presence of
      anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power
      fields, Ki-67 > or = 10%, and Ki-67 "hot spot" > or = 25% were associated with
      decreased metastasis-free or overall survival. Ploidy status was not associated
      with any adverse outcome. The presence of any of these adverse prognostic factors
      can indicate the possibility of a more aggressive behavior in extraskeletal
      myxoid chondrosarcoma, and a closer follow-up is suggested.

PMID- 10955459
TI  - Necrotizing sarcoid granulomatosis mimicking an intracranial neoplasm:
      clinicopathologic features and review of the literature.
AB  - We present a unique case of biopsy-proven necrotizing sarcoidosis involving the
      central nervous system (CNS) in a 52-year-old woman. The patient presented with a
      3-month history of left-sided headache and sharp, shooting pains on the left side
      of her face. She also has a previous history of sarcoidosis, histopathologically
      confirmed on parotid gland biopsy 24 years before. Imaging studies of the present
      lesion revealed a 1.8 x 1.4-cm mass in the left temporal lobe with signal
      intensity suggestive of meningioma or low-grade glial neoplasm. Surgical
      resection was initiated, and intraoperative consultation with frozen sections
      revealed granulomata. The lesion was biopsied, and surgical intervention was
      terminated. Permanent sections failed to reveal bacteria, mycobacteria, fungi, or
      foreign bodies. A diagnosis of necrotizing neurosarcoidosis was rendered. The
      patient was administered steroid therapy and clinically responded favorably. At
      the most recent follow-up almost 2 years later, there was no evidence of
      recurrence or progression. Necrotizing sarcoidosis has been reported most
      commonly in the lungs and rarely in other organ systems. We report the first
      histologically proven case involving the CNS as well as a rare example of
      sarcoidosis and necrotizing sarcoid granulomatosis in the same patient.
      Sarcoidosis and its necrotizing variant should be considered in the differential
      diagnosis of a granulomatous mass lesion involving the CNS, particularly in the
      context of a history of systemic disease.

PMID- 10955460
TI  - Squamous cell carcinoma arising in recurrent respiratory papillomatosis with
      pulmonary involvement: emerging common pattern of clinical features and human
      papillomavirus serotype association.
AB  - Squamous papillomas of the lung are an uncommon feature of recurrent respiratory
      papillomatosis, occurring in fewer than 1% of cases. We describe a 23-year-old
      patient with pulmonary papillomas who developed a fatal squamous cell carcinoma
      of the lung. PCR-based human papillomavirus (HPV) typing showed the presence of
      HPV 11 DNA in both benign papillomas and invasive carcinoma. A review of the
      literature reveals four reports of malignant transformation of juvenile-onset
      recurrent respiratory papillomatosis in which HPV typing was performed. Similar
      clinical features are noted in all of the reports; specifically, each case has
      arisen in a young adult man with a history of papillomatosis since childhood. In
      each of the cases, HPV 11 was identified in association with the squamous cell
      carcinoma. Although HPV 11 is uncommonly associated with the development of
      invasive carcinoma at other sites, these findings suggest that it is correlated
      with malignant transformation in the setting of juvenile-onset recurrent
      respiratory papillomatosis.

PMID- 10955461
TI  - Correspondence Re: Lack EE, Askin FB, Dehner LB, Page DL, Weiss LM.
      Recommendations for reporting of tumors of the adrenal cortex and medulla. Mod
      Pathol 1999:12:835-9.

PMID- 10955462
TI  - Abstracts. Mod Pathol 2000;13:17A,19A,22A,24A,25A,27A.

PMID- 10955463
TI  - Total ankle arthroplasty: indications, results, and biomechanical rationale.
AB  - Total ankle replacement was developed in the 1970s after the success of total hip
      and knee arthroplasty. The goal of total ankle arthroplasty is to decrease pain
      and improve function in the lower limb. Ideally, to be superior to an
      arthrodesis, the ankle replacement should provide the patient with good patterns
      of joint motion and the ability to walk and run and should have low complication
      rates. Unfortunately, total ankle arthroplasty has not been as successful as
      replacement of other joints. Published studies of early series with greater
      follow-up show that ankle arthroplasties did not provide lasting pain relief or
      improve function, and most ultimately failed. During the 1980s, many authors
      concluded that a total ankle arthroplasty was not warranted because of the
      generally poor long-term results and the high rate of complications. However,
      newer second-generation design techniques, innovative operative procedures, and
      dissatisfaction with the results of ankle arthrodesis have renewed interest in
      total ankle arthroplasties. This review describes the numerous types of ankle
      joint replacements, critically reviews the results, and reports on newer
      prostheses that incorporate more anatomic designs.

PMID- 10955464
TI  - Total ankle replacement: a surgical discussion. Part I. Replacement systems,
      indications, and contraindications.

PMID- 10955465
TI  - Total knee arthroplasty ligament balancing and gap kinematics with posterior
      cruciate ligament retention and sacrifice.
AB  - This cadaver study was undertaken to gain insight into the effects that posterior
      cruciate ligament retention and sacrifice would have on the amount of deformity
      correction obtained with medial and lateral structure release during total knee
      arthroplasty. Twenty-seven cadaveric specimens were used to sequentially release
      medial and lateral structures with and without posterior cruciate support. Each
      release sequence was tested in full extension and 90 degrees flexion. In full
      extension, the resulting change into valgus after release of the posterior
      cruciate ligament, posteromedial capsule/oblique ligament complex, superficial
      medial collateral ligament, and pes anserinus and semimembranosus tendons was 6.9
      degrees, and it increased to 13.4 degrees in 90 degrees flexion. With
      preservation of the posterior cruciate ligament this decreased to 5.2 degrees in
      extension and 8.7 degrees in flexion. Changes seen in 90 degrees flexion were
      significantly greater than those in full extension. For the valgus knee model
      with release of the posterior cruciate ligament, posterolateral capsule, lateral
      collateral ligament, iliotibial band, popliteus tendon, and lateral head of the
      gastrocnemius, 8.9 degrees of change into varus was seen in extension and 18.1
      degrees in 90 degrees flexion. With posterior cruciate ligament retention 5.4
      degrees and 4.9 degrees of change into varus was seen in extension and flexion,
      respectively. Significantly less change with retention of the posterior cruciate
      ligament was seen with both medial and lateral release and more opening of the
      flexion gap was seen on the release side of the joint for all groups except those
      with lateral release with sacrifice of the posterior cruciate ligament.

PMID- 10955466
TI  - Instrumented posterior arthrodesis of the lumbar spine in patients with diabetes
      mellitus.
AB  - The existence of diabetes mellitus has been postulated to have a deleterious
      effect on the outcome following lumbar spine surgery. We retrospectively examined
      the records and radiographs of 32 diabetic patients (mean age, 60 years) who
      underwent posterior lumbar fusions using transpedicular instrumentation and iliac
      crest autograft. Ten patients were insulin-dependent and 22 required oral
      hypoglycemic agents for at least 1 year prior to surgery. The minimum follow-up
      time was 2 years after surgery (mean, 2.5 years). Surgical indications included
      herniated lumbar disk, lumbar spinal stenosis, thoracolumbar trauma, and lumbar
      pseudarthrosis. Clinical results were evaluated by chart review and/or interview
      by using Odom's criteria. At follow-up, 75% of patients were graded as excellent
      or good, and 25% as fair or poor. Twenty-five of 32 patients (78%) had
      improvement of back pain. Twenty of 27 (74%) patients had improvement of leg
      pain. Eight of 15 (53%) patients had improvement in motor strength, and 6 of 11
      (54%) had improvement in light-touch sensation. Insulin dependence and the
      presence of polyneuropathy were associated with a poorer outcome. The average
      time to radiographic fusion was 5 months. Twenty-nine of 32 patients (91%)
      developed solid fusion by strict radiographic criteria. The three patients with a
      pseudarthrosis had persistent back pain and a poor result. Ten of 32 (31%) of the
      patients experienced perioperative complications, including prolonged wound
      drainage (n = 5), deep wound infection (n = 1), superficial wound infection (n =
      1), atrial fibrillation (n = 1), ruptured cerebral aneurysm (n = 1), and ulnar
      nerve neuropathy (n = 1). We conclude that posterolateral lumbar spinal fusion
      with internal fixation in diabetic patients yields clinical results comparable to
      those of nondiabetic patients, with similar risks of perioperative complications.

PMID- 10955467
TI  - Computed tomographic evaluation of length of screw paths for anterior cervical
      plating.
AB  - Thirty patients' computed tomographic (CT) scans of the cervical spine were used
      to measure screw path lengths with respect to anterior plating. The results
      indicated that all screw paths were longer in men than in women, and the majority
      of lengths differed significantly by sex (P < or = .05). The mean length of the
      sagittal, parasagittal, and convergent screw paths for both men and women was 16
      mm. The mean length of the safe divergent screw path was 15 mm. Therefore, the
      safe screw length may be 16 mm for convergent placement and 15 mm for divergent
      placement. Convergent screw placement is recommended. Preoperative CT or magnetic
      resonance imaging evaluation and measurement of the intended screw trajectories
      are recommended.

PMID- 10955468
TI  - Open tongue-type calcaneus fracture with a partial posteromedial subtalar
      dislocation.
AB  - Calcaneus fractures with a subtalar dislocation are extremely rare. A case of a
      tongue-type calcaneus fracture with a posteromedial dislocation of the calcaneal
      posterior facet and tuberosity is presented. Treatment included lag screw
      fixation to maintain the reduction without further soft-tissue trauma.

PMID- 10955469
TI  - Limb salvage using distraction osteogenesis.
AB  - Distraction osteogenesis is a novel technique for the biological restoration of
      segmental bone defects. Definitive treatment of musculoskeletal tumors often
      requires large bony resections that can leave patients with significant osseous
      defects. Limb salvage using distraction osteogenesis is an attractive
      reconstructive alternative that may, in fact, offer advantages over other
      conventional techniques. We present our initial experience with the use of
      distraction osteogenesis in limb salvage.

PMID- 10955470
TI  - Surgical management of posterior shoulder instability in a ten-year-old boy: a
      case report and literature review.
AB  - Posterior shoulder instability is an uncommon clinical entity. It is even more
      rare in the pediatric population. We report the case of a 10-year-old boy who
      experienced recurrent posttraumatic posterior shoulder instability that
      eventually required surgical intervention. A review of the literature revealed no
      previous report of surgical management of nonobstetrical posttraumatic posterior
      glenohumeral instability in a skeletally immature individual.

PMID- 10955471
TI  - Surgical repair of a traumatic latissimus dorsi avulsion: a case report.
AB  - We report a case of traumatic avulsion of the latissimus dorsi tendon in a
      professional body-builder. The injury was repaired by reattachment of the avulsed
      tendon. This procedure is quite challenging in a well-muscled individual and
      requires a detailed understanding of the anatomy of the axilla.

PMID- 10955472
TI  - Transcaphoid-perilunate fracture dislocation.

PMID- 10955473
TI  - Maternal chromosome 7 hetero/isodisomy in Silver-Russell syndrome and PEG1
      biallelic expression.
AB  - Silver-Russell syndrome (SRS) is characterized by a severe intrauterine and
      postnatal growth retardation, relative macrocephaly associated with 'mild' facial
      anomalies. The diagnostic importance of skeletal asymmetry remains controversial.
      The aetiology of the syndrome is heterogeneous. Maternal uniparental disomy of
      chromosome 7 (mUPD7) has been reported in approximately 7% of patients, but two
      carriers of chromosomal abnormalities involving the band 17q25 have also been
      described. We investigated a clinically selected sample of 20 SRS patients for
      the presence of mUPD7 using polymorphic microsatellite markers spanning the whole
      chromosome. Maternal UPD7 was found in only one patient corresponding to an
      incidence of 5%. The allelic distribution in this patient was consistent with
      heterodisomy. Segregation analysis of chromosome 14 and 16 showed a biparental
      contribution in all the 20 patients. Blood RNA from the mUPD7 patient and a
      normal donor were evaluated for the expression of Paternally Expressed Gene
      (PEG1), an imprinted gene on chromosome 7q32. Biallelic expression of the gene in
      adult blood tissues was found in both samples. Our results confirm the causal
      role of mUPD7 in a minority of SRS patients.

PMID- 10955474
TI  - The Pallister-Killian syndrome is reliably diagnosed by FISH on buccal mucosa.
AB  - The Pallister-Killian syndrome is a rare disorder, which is clinically diagnosed
      and usually confirmed by the detection of mosaicism for an isochromosome 12p in
      fibroblast cultures. To date FISH on buccal mucosa has been used in only three
      cases and this detected high levels of mosaicism for the isochromosome. We review
      one previously reported case [Woodman et al. (1995) Genet Couns 6:33-36] and
      report a further seven clinically suspected cases in which the diagnoses were
      confirmed by FISH on buccal mucosa, and recommend that this tissue be used
      routinely for laboratory confirmation. The presence of the isochromosome 12p at
      levels as low as 1% is acceptable.

PMID- 10955475
TI  - Spondylometaphyseal dysplasia Sedaghatian type associated with lethal arrhythmia
      and normal intrauterine growth in three siblings.
AB  - Spondylometaphyseal dysplasia of the Sedaghatian type is a rare dysplasia,
      characterized by mild limb shortening, but lethal in the neonatal period. We
      describe three affected male siblings, the offspring of consanguineous parents.
      One was stillborn. Neonatal death was due to cardiac arrhythmia in two of the
      siblings. This report confirms the importance of cardiac pathology in this
      probably autosomal recessive disorder. This diagnosis should be excluded in any
      newborn with an arrhythmia as the clinical limb shortening may not be obvious.

PMID- 10955476
TI  - Short limbed skeletal dysplasia associated with combined immunodeficiency and
      congenital subglottic stenosis: a new constellation of features.
AB  - A newborn male is described with an association of short limbed dwarfism with hip
      dislocation, combined immunodeficiency characterized by absent B cells and CD4
      lymphopaenia and congenital subglottic stenosis. This constellation of
      abnormalities is distinct from other described skeletal dysplasias associated
      with immunodeficiency such as ADA deficiency and cartilage hair hypoplasia.

PMID- 10955477
TI  - Char syndrome: a new family and review of the literature emphasising the presence
      of symphalangism and the variable phenotype.
AB  - We report a family of three affected individuals with the facial features of Char
      syndrome. The family also demonstrates symphalangism of the distal
      interphalangeal joints of the fifth fingers, extending the digital phenotype seen
      in this condition. We review the features of previously reported patients and
      emphasise the variability in the phenotype of Char syndrome.

PMID- 10955478
TI  - A new syndrome of optic nerve colobomas and renal abnormalities associated with
      arthrogryposis multiplex.
AB  - Renal-coloboma syndrome is a developmental disorder involving optic nerve
      colobomas and renal hypoplasia/insufficiency, which exhibits autosomal dominant
      inheritance and a highly variable phenotype (OMIM:120330). Mutation in the PAX2
      gene was found to result in the renal-coloboma phenotype. We report on an Arab
      family with autosomal dominant inheritance of a syndrome characterized by a
      variable combination of optic nerve colobomas, renal abnormalities,
      vesicoureteral reflux, lax joints and arthrogryposis multiplex. Apart from the
      arthrogryposis multiplex which has not been described in the renal-coloboma
      syndrome, the features of the syndrome in this family are very similar to the
      renal-coloboma syndrome. However sequencing of all 12 axons of PAX2 gene revealed
      no mutation in this family. The disorder in this family is likely to represent a
      new syndrome with features overlapping with the renal-coloboma syndrome.

PMID- 10955479
TI  - An unknown combination of infantile spasms, retinal lesions, facial dysmorphism
      and limb abnormalities.
AB  - A female patient is presented with infantile spasms, punched-out retinal lesions,
      facial dysmorphism, short upper arms, short thumbs, left lower limb hypoplasia
      with foot deformity, a hemivertebra, atrial septal defect, growth retardation and
      severe developmental delay. There is some similarity to patients with Aicardi
      syndrome (AS), but the retinal lesions in our patient are different and she does
      not have agenesis of the corpus callosum, one of the diagnostic features of AS.
      She might represent an atypical form of this syndrome with additional features,
      usually not present in AS. As there is no diagnostic test for AS yet, this
      diagnosis cannot be confirmed nor rejected with certainty. However, it might be
      more likely that our patient has another, possibly unique, condition.

PMID- 10955480
TI  - 22q11 deletion and polymicrogyria--cause or coincidence?
AB  - We report a familial case of velocardiofacial syndrome (VCFS) with polymicrogyria
      to provide further support for the association of disorders of cortical
      development with del(22q11) syndromes.

PMID- 10955481
TI  - A boy with mental retardation, blepharophimosis and hypothyroidism: a diagnostic
      dilemma between Young-Simpson and Ohdo syndrome.
AB  - We report a male infant with an association of hypothyroidism and unusual facies,
      including blepharophimosis, which is similar to the dysmorphic features observed
      in the condition first described by Young and Simpson [(1987) J Med Genet 24:715
      7161. On the other hand, the patient also shares many features with those
      reported as having Ohdo blepharophimosis syndrome [Ohdo et al, (1986) J Med Genet
      23:242-244]. Previous case reports are reviewed and difficulties concerning the
      differential diagnosis of these conditions are discussed.

PMID- 10955482
TI  - Tibial aplasia--VACTERL association, a new syndrome?
AB  - We report on a male infant, born to nonconsanguineous parents, with a vertebral
      anomaly, cardiac defect, tracheo-oesophageal fistula and hypospadias (VACTERL
      association) together with bilateral tibial aplasia. This pattern of
      abnormalities appears to represent a unique syndrome.

PMID- 10955483
TI  - A case of the new overgrowth syndrome--macrocephaly with cutis marmorata,
      haemangioma and syndactyly.
AB  - Moore et al. [(1997) J Med Genet 70:67-73] and Clayton-Smith et al. [(1997) Clin
      Dysmorphol 6:291-302] have recently described a new overgrowth syndrome with
      macrocephaly, cutis marmorata, haemangiomas and digit syndactyly. Other features
      have included body asymmetry, hydrocephalus requiring shunting and developmental
      delay. All 22 cases reported are sporadic. We report a further case of this rare
      syndrome.

PMID- 10955484
TI  - Bullous ichthyosiform erythroderma, developmental delay, aortic and pulmonary
      stenosis in association with a FRA12A.
AB  - We present an 11-year-old female with bullous ichthyosiform erythroderma (BIE),
      learning disability, patent ductus arteriosus and mild stenosis of the aortic and
      pulmonary arteries. Chromosome analysis showed the expression of the rare folate
      sensitive fragile site FRA12A at 12q13 in 8/20 (40%) of blood lymphocytes
      cultured in folate-deficient medium in the presence of trimethoprim. Her mother
      and maternal grandmother are phenotypically normal, but her mother shows
      expression of the same fragile site in 4/20 (20%) of cells cultured under the
      same conditions. Lymphocytes from the grandmother only showed expression of the
      fragile site when cultured in the presence of methotrexate in folate deficient
      medium. Interestingly, two genes (keratin 1 and keratin 2e) which are known to
      cause BIE map to 12q13. Molecular data is presented excluding three candidate
      (CCG)n repeats within keratin 1 gene. We present a review of previously reported
      FRA12A cases and discuss possible molecular explanations for the clinical
      findings in this patient.

PMID- 10955485
TI  - A new case of acromegaloid facial appearance (AFA) syndrome with an expanded
      phenotype.
AB  - A patient presenting with the findings of Acromegaloid Facial Appearance (AFA)
      syndrome is reported. This case also shows pericardial effusion and skin lesions
      that both enlarge the spectrum of the phenotype and lump AFA syndrome with
      another proposed distinct condition [Irvine et al., (1996) J med Genet 33:972
      974].

PMID- 10955486
TI  - Craniofacial dysmorphism, agenesis of the corpus callosum and ocular colobomas:
      Temtamy syndrome?
AB  - A possible new case of Temtamy syndrome is described in a male child. Clinical
      features of the present case and those described by Temtamy are discussed.

PMID- 10955487
TI  - Type 1 sirenomelia in one of male twins, with imperforate anus in the other male
      twin.
AB  - The etiology of sirenomelia sequence is still obscure. The role of maternal
      diabetes and a vascular steal phenomenon have been discussed [Gurakan et al.
      (1996) Turk J Pediatr 38:393-397]. Discordant monozygotic twin sirenomelia has
      been commonly reported but only rarely in dizygotic twins. The family of the
      presented twins had a high risk of diabetes mellitus. One of the twins has type 1
      sirenomelia and the other had only an imperforate anus.

PMID- 10955488
TI  - Ulnar deviation of the thumb: an exceptional finding in Rubinstein-Taybi
      syndrome.
AB  - A 2-year-old girl with Rubinstein-Taybi syndrome and the unusual finding of ulnar
      deviation of the thumb is described. Possible modes of inheritance are discussed.

PMID- 10955489
TI  - SOX9 mutation in a previously published case of campomelic dysplasia without
      overt campomelia.
AB  - An SOX9 mutation in a previously published case of campomelic dysplasia is
      described. This case did not have overt campomelia of the femora or tibiae
      although campomelic dysplasia has subsequently been confirmed by gene analysis.

PMID- 10955490
TI  - Magnetic resonance imaging features of brain stem abscessation in two cats.
AB  - Premortem magnetic resonance imaging (MRI) was performed in two cats with brain
      stem abscessation confirmed post mortem by histology and recovery of multiple
      bacterial species. The MRI features of the abscesses were distinctive and
      included a thick and marked enhancement of the abscess capsule and extension of
      the lesion from a tympanic bulla in one cat. A focal area of increased signal
      intensity was present on T2-weighted images. A circumscribed area of decreased
      signal intensity was surrounded by a ring of increased signal intensity on
      precontrast T1-weighted images. A center of decreased signal intensity with a
      thick, markedly enhanced abscess capsule was observed on post contrast T1
      weighted images. These findings are compared to the current experimental and
      clinical literature of brain abscess. The underlying pathogenesis of MRI features
      is reviewed.

PMID- 10955491
TI  - Comparison of fast spin-echo and conventional spin-echo magnetic resonance spinal
      imaging techniques in four normal dogs.
AB  - Various magnetic resonance (MR) imaging techniques have been used to assess
      lumbar spinal abnormalities in people. Four, young adult, clinically normal dogs
      were used to compare images of the spinal cord acquired using conventional spin
      echo and rapid acquisition relaxation-enhanced (RARE), commonly called fast spin
      echo (FSE), magnetic resonance imaging techniques. Lateral myelograms were made
      as an anatomic control. The T2-weighted FSE technique was characterized by better
      image quality than the T2-weighted conventional spin-echo technique. The short
      acquisition time with the FSE technique allowed increases in the matrix size and
      number of excitations, thus improving resolution and signal-to-noise ratio. In
      canine lumbar spinal MR imaging, use of a FSE technique is recommended to reduce
      the overall time for imaging and to improve image quality.

PMID- 10955492
TI  - Magnetic resonance imaging and cross sectional anatomy of the normal equine
      sinuses and nasal passages.
AB  - The purpose of this investigation was to define the magnetic resonance imaging
      anatomy of the rostral part of the equine head. 10 mm-thick, T1-weighted images
      of two isolated equine cadaver heads were obtained using a 1.5 Tesla magnet and a
      body coil. MR images were compared to corresponding frozen cross-sections of the
      cadaver head. Relevant anatomic structures were identified and labeled at each
      level. The resulting images provided excellent anatomic detail of the oral and
      nasal cavities, paranasal sinuses and associated structures. Annotated MR images
      from this study are intended as a reference for clinical MR imaging studies of
      the equine head.

PMID- 10955493
TI  - Radiographic and echocardiographic measurement of the heart in obese cats.
AB  - A prospective study was undertaken to reconcile radiographic cardiomegaly and
      normal echocardiography in obese cats and to test a radiographic technique for
      better distinguishing between pericardial fat and the heart. Ten obese, but
      otherwise normal cats and 10 non-obese normal cats were used. A body condition
      scoring system was used to objectively group obese and non-obese normal cats. Two
      dimensional echocardiograms were made to verify that all cats had a normal heart.
      Thoracic radiographs then were made using standard and altered exposure
      techniques. The hearts were measured on these radiographs using the metric and a
      vertebral scale system. Obese cats consistently had excessive fat around the
      heart especially if they also had a large amount of falciform fat. Altering
      exposure technique by increasing mAs and decreasing kVp sometimes enhanced the
      radiographic contrast between fat and myocardium. Enhanced radiographic contrast
      accentuated the double silhouette identifying the true cardiac silhouette within
      the fat expanded silhouette. Pericardial fat usually was distinguished more
      readily in lateral than in VD radiographs. In two cats, pericardial fat had a
      characteristic prominent square corner to the right cranial margin of the cardiac
      silhouette in VD radiographs. Obesity caused increased width and depth of the
      thoracic cage. 2D echocardiograms revealed normal cardiac dimensions in both
      groups of cats and increased precordial distance in the obese group.

PMID- 10955494
TI  - Radiographic diagnosis: nasopharyngeal foreign body in a dog.

PMID- 10955495
TI  - Imaging of a cat with perirenal pseudocysts.
AB  - A 16-year-old, neutered male, domestic short hair cat had abdominal distension
      and systemic hypertension. Radiography, ultrasonography, excretory urography, and
      renal scintigraphy were performed to establish the diagnosis and implement
      appropriate treatment. Bilateral perirenal pseudocysts were confirmed surgically
      and histopathologically. Following bilateral renal capsulectomy, systemic
      hypertension decreased and global glomerular filtration rate improved to normal
      limits. Multiple imaging modalities helped establish the diagnosis and guided
      implementation of appropriate treatment.

PMID- 10955496
TI  - Nodular fat necrosis in the feline and canine abdomen.
AB  - The radiographic appearance of nodular fat necrosis is described in ten cats and
      one dog. The most common radiographic sign was the presence of a focal
      mineralized circular to oval soft tissue mass in the abdominal fat as present in
      9 cats. These masses had a distinct eggshell-like rim encapsulating the lesion.
      In one cat and one dog multiple masses were present, without radiographic signs
      of mineralization. Abdominal ultrasound was performed in three cats and one dog,
      findings included the presence of hyperechoic masses with associated acoustic
      shadowing, some with a hypoechoic centre. Almost all animals were old and obese.
      In three cats and one dog, changes were confirmed with biopsy or post mortem
      examination. Lesions having the appearance of those in this paper are most likely
      incidental findings and should not be confused with abdominal masses of
      neoplastic origin. Ultrasound can be helpful in identifying such lesions.

PMID- 10955497
TI  - Radiology corner: differential diagnosis of pulmonary cavitary lesions.

PMID- 10955498
TI  - Radiology corner: obstruction of contrast medium flow during cervical
      myelography.

PMID- 10955499
TI  - Retrospective review of the ultrasonographic features of adrenal lesions in 21
      ferrets.
AB  - Clinical signs and follow-up information were recorded. Histopathologic diagnoses
      were obtained for 25 adrenal glands in 21 ferrets. Adrenal lesions included ten
      adenocarcinomas, nine adenomas, one hyperplasia and one cortical cyst. Four
      adrenal glands (all right-sided) were diagnosed as unspecified adrenal tumors but
      lacked a definite histopathologic diagnosis (adenoma vs. adenocarcinoma) due to
      incomplete surgical resection and consequent small sample sizes. Bilateral
      adrenal lesions were identified in 4 ferrets (19%). Adrenal shape, size,
      echogenicity, laterality, and the presence of vascular invasion were evaluated
      with ultrasound. Size and shape were variable and not specific to lesion type.
      Both benign and malignant adrenal tumors (adenomas, adenocarcinomas) appeared
      most often as masses with increased thickness and a normal length (11/23), less
      frequently as larger masses with increased thickness and length (4/23) or as
      nodules focally deforming the normal adrenal shape (6/23). The only cortical cyst
      appeared as a nodule. Three adrenal glands had a normal size and shape and were
      diagnosed as adenomas (2) or hyperplasia (1). Therefore treatment may be
      warranted based solely on clinical signs if adrenal glands are
      ultrasonographically normal. Vascular invasion was not identified
      ultrasonographically. However, focal absence of periglandular fat resulting in
      contact of 8 adrenal glands with either caudal vena cava (6), aorta (1) or liver
      (1) identified ultrasonographically, correlated with incomplete surgical
      resectability (6/8) and histopathologic diagnoses of carcinoma (4/8) or
      unspecified tumors (4/8). Therefore, a focal absence of periglandular fat between
      the adrenal gland and the large vessels or liver, deviation or compression of the
      large vessels by the adrenal lesion may indicate malignancy. Adrenal tumors
      (benign and malignant) were often associated with a prominent uterus, uterine
      stump or prostate with or without prostatic cysts.

PMID- 10955500
TI  - Scintigraphic detection of equine orthopedic infection using Tc-HMPAO labeled
      leukocytes in 14 horses.
AB  - The aim of this study was to evaluate the diagnostic value of 99mTc-HMPAO
      leukocyte scintigraphy (LS) by means of a retrospective review of its use in 14
      horses that were evaluated for orthopedic infection as a cause of lameness. A
      total of 17 LS exams were performed in 14 horses. LS studies were positive in 10
      of 14 horses. A bacterial infection was confirmed with cytology or culture in 9
      of 10 positive horses. Negative LS studies occurred in 4 of 14 horses. Necropsy
      confirmed the lack of infection in 2 of the 4 horses. Other clinical data and a
      favorable clinical outcome supported a negative study in the other 2 horses. No
      false negative or false positive studies were identified. It may be concluded
      that HMPAO-LS is an effective tool for the diagnosis of orthopedic infection in
      horses.

PMID- 10955501
TI  - The application of technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO)
      labeled white blood cells for the diagnosis of right dorsal ulcerative colitis in
      two horses.
AB  - The application of 99mTc-HMPAO labeled white blood cells to support the diagnosis
      of right dorsal ulcerative colitis was studied in two horses with a history and
      clinical signs consistent with phenylbutazone toxicity. These images were
      compared to a reference horse unaffected by right dorsal ulcerative colitis.
      Blood was collected aseptically in heparinized syringes from the patients for in
      vitro white blood cell (WBC) radiolabeling. The buffy coat was separated out and
      radiolabeled with 99mTc-HMPAO. The radiolabeled blood was re-injected i.v. and
      four images of the right and left side of the patient's abdomen were acquired at
      4 hours and 20 hours post-injection. Results of the nuclear study revealed no
      abnormal findings in the abdomen at the four-hour post-injection images in any
      horse. Images obtained 20 hours post-injection revealed a linear uptake of
      radiolabeled WBCs in the right cranioventral abdomen in the region of the right
      dorsal colon in both horses with right dorsal ulcerative colitis. The reference
      horse had no radiopharmaceutical uptake in this region. This nuclear imaging
      study was a rapid, non-invasive method to identify right dorsal colon
      inflammation. These findings not only supported the diagnosis of right dorsal
      ulcerative colitis, but also facilitated appropriate medical management of each
      horse.

PMID- 10955502
TI  - Effects of a digital filter on detectability of a phantom lesion in a scintigram
      of the equine tarsus.
AB  - The aim of this study was to examine the effects of a digital filter on the
      detectability of a phantom lesion in a scintigram of the equine tarsus. Lateral
      images containing 50, 100, 150, 500, or 1000 kcounts were acquired. A created
      phantom lesion of 0 (normal), 10, 15, 20, or 30% increased intensity relative to
      local background was placed in the centrodistal tarsal joint area in the images
      of different count levels. Duplicate images were filtered with a Metz filter. The
      complete set of filtered and unfiltered images totaling 180 images was projected
      as slides to a group of 9 observers. The sensitivity in 50 and 100 kcount images
      was improved by applying the filter. Digital filtering increased the false
      positive fraction at all count levels but this effect was most pronounced in 500
      and 1000 kcount images. Based on receiver operating characteristic analysis,
      filtering of a 50 kcount image improved image quality to that of a 150 kcount
      image.

PMID- 10955503
TI  - Comparison of the accuracy of positioning devices for radiation therapy of canine
      and feline head tumors.
AB  - The purpose of this retrospective study was to evaluate the repositioning
      accuracy of different positioning devices in order to determine their
      applicability for potential use in conformal radiation therapy for animals. Forty
      four animals with spontaneous tumors of the head were included. The animals were
      divided into 3 groups determined according to the positioning device used. Group
      1 animals were positioned using a thermoplastic mask. Group 2 animals were
      positioned using a head holder. Group 3 animals were positioned using the head
      holder and an inflatable pillow. The time of presentation determined which
      position device was used. Port films of the 44 patients were reviewed
      retrospectively, and the repositioning precision was recorded by measurements in
      three orthogonal planes. Groups 2 and 3 had significantly better repositioning
      accuracy (P < or = 0.05) compared to Group 1. The position variation was not
      significantly different (P < or = 0.05) between Groups 2 and 3 in the lateral and
      longitudinal direction. Group 3 had a median reposition variation of 0.5 to 1.0
      mm, with a standard deviation of 1.0 to 1.5 mm.

PMID- 10955504
TI  - Primary irradiation of canine intracranial masses.
AB  - Twenty-nine dogs received primary radiation therapy for intracranial lesions and
      clinical signs suggestive of neoplasia. Presumptive diagnosis and tumor
      categorization was based on computed tomographic or magnetic resonance images.
      Meningioma was the most likely tumor type in 22 dogs and glioma or choroid plexus
      tumors were tentatively identified in 4 and 3 dogs, respectively. Cobalt-60
      radiation was delivered in 3 Gy fractions on a daily, Monday-through-Friday basis
      for a total dose of 48 Gy (16 fractions) in 28 dogs; one dog received 54 Gy. Two
      of 29 dogs died during treatment of signs suggestive of progressive tumor growth
      but were included in the overall evaluation of response to treatment. Median
      overall survival was 250 days (range 21-804). Mild acute radiation effects on
      normal tissue developed and did not influence outcome in any dog. Late radiation
      effects could not be evaluated in this study. No significant predictive
      indicators were identified from the clinical or imaging data. Radiation therapy
      is superior to medical treatment of brain tumors in dogs with steroids, is useful
      for tumors that are not currently operable and may be preferable to surgical
      resection in dogs if the mass appears infiltrative. However, 22/29 (76%) dogs
      died of recurrent progressive neuropathy suggestive of tumor regrowth or
      progression. Thus, alternative methods for delivery of radiation to dogs with
      brain tumors or novel combinations of therapy should continue to undergo
      evaluation.

PMID- 10955505
TI  - Gastric emptying of BIPS in normal dogs with simultaneous solid-phase gastric
      emptying of a test meal measured by nuclear scintigraphy.

PMID- 10955506
TI  - A precolumn derivatization high-performance liquid chromatographic method with
      improved sensitivity and specificity for the determination of astragaloside IV in
      Radix Astragali.
AB  - A reversed-phase high-performance liquid chromatographic method is developed for
      the determination of astragaloside (AGS) IV, which is known as the active
      constituent of Radix Astragali. The method uses precolumn derivatization with
      benzoyl chloride to form the benzoyl ester of AGS IV quantitatively and is
      carried out with a wide-ranging concentration (0.004-0.080 mg/mL) of the
      derivatized AGS IV. The eluent consists of 90% methanol, 4% tetrahydrofuran, 6%
      water, and 0.2% triethylamine, with vitamin D3 added as the internal standard.

PMID- 10955507
TI  - Chromatographic and mass spectral methods of identification for the side-chain
      and ring regioisomers of methylenedioxymethamphetamine.
AB  - The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) is one of a
      total of 10 regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines of MW 193
      that yields regioisomeric fragment ions with equivalent mass (m/z 58 and 135/136)
      in the electron-impact (EI) mass spectrum. Thus, these 10
      methylenedioxyphenethylamines are uniquely isomeric; they have the same molecular
      weight and equivalent major fragments in their mass spectra. The specific
      identification of one of these compounds (i.e., Ecstasy or 3,4-MDMA) in a
      forensic drug sample depends upon the analyst's ability to eliminate the other
      regioisomers as possible interfering or coeluting substances. This study reports
      the synthesis, chemical properties, spectral characterization, and
      chromatographic analysis of these 10 unique regioisomers. The ten 2,3- and 3,4
      regioisomers of MDMA are synthesized from commercially available precursor
      chemicals. In the EI mass spectra, the side-chain regioisomers show some
      variation in the relative intensity of the major ions, with the exception of only
      one or two minor ions that might be considered side-chain specific fragments. The
      position of substitution for the methylenedioxy ring is not easily determined by
      mass spectral techniques, and the ultimate identification of any one of these
      amines with the elimination of the other nine must depend heavily upon
      chromatographic methods. The chromatographic separation of these 10 uniquely
      regioisomeric amines are studied using reversed-phase liquid chromatographic
      methods with gradient elution and gas chromatographic techniques with temperature
      program optimization.

PMID- 10955508
TI  - High-performance liquid chromatographic determination of amphotericin B in a
      liposomal pharmaceutical product and validation of the assay.
AB  - A validated high-performance liquid chromatographic method is presented to
      quantitate amphotericin B (AB) in a liposomal pharmaceutical formulation. The
      analysis is based on the chromatographic separation of AB and 1-amino-4
      nitronaphthalene (the internal standard) on a C18 muBondapac reversed-phase
      column with a mobile phase consisting of a mixture of acetonitrile and 0.02 M
      ethylenediamine tetra-acetic acid disodium salt at pH 5.0 (45:55, v/v). The
      chromatographic analysis time is less than 10 min, and the validation of the
      assay shows that it is selective, accurate, and linear for the concentration
      range of 2.50 to 7.50 microg/mL with a detection limit of 0.00500 microg/mL. The
      within-day and between-day relative standard deviation values are 1.26% (n = 18)
      and 1.25% (n = 8), respectively. The method described conforms to the validation
      of compendial methods used for finished pharmaceutical products in general and
      offers a reliable, quick, and cost-effective procedure for examining the
      consistency or quality-control analysis of AB in liposomal products. It can also
      be applied for the determination of AB in other nonliposomal lipid-based drug
      delivery systems that are on the market.

PMID- 10955509
TI  - Simultaneous determination of sweeteners and preservatives in preserved fruits by
      micellar electrokinetic capillary chromatography.
AB  - A micellar electrokinetic capillary method for the simultaneous determination of
      the sweeteners dulcin, aspartame, saccharin, and acesulfame-K and the
      preservatives sorbic acid; benzoic acid; sodium dehydroacetate; and methyl-,
      ethyl-, propyl-, isopropyl-, butyl-, and isobutyl-p-hydroxybenzoate in preserved
      fruits is developed. These additives are ion-paired and extracted using
      sonication followed by solid-phase extraction from the sample. Separation is
      achieved using a 57-cm fused-silica capillary with a buffer comprised of 0.05 M
      sodium deoxycholate, 0.02 M borate-phosphate buffer (pH 8.6), and 5%
      acetonitrile, and the wavelength for detection is 214 nm. The average recovery
      rate for all sweeteners and preservatives is approximately 90% with good
      reproducibility, and the detection limits range from 10 to 25 microg/g. Fifty
      preserved fruit samples are analyzed for the content of sweeteners and
      preservatives. The sweeteners found in 28 samples was aspartame (0.17-11.59 g/kg)
      or saccharin (0.09-5.64 g/kg). Benzoic acid (0.02-1.72 g/kg) and sorbic acid
      (0.27-1.15 g/kg) were found as preservatives in 29 samples.

PMID- 10955510
TI  - On-line monitoring of wastewater using ion chromatography.
AB  - Ion Chromatography (IC) has been used for the on-line determination of anions and
      cations in a variety of process streams. On-line monitoring of process and
      wastewater streams optimizes the control of treatment methods by providing early
      indications of problems that could increase discharges of hazardous compounds to
      the environment. It is important for the immediate detection and remediation of
      process upsets in critical streams. The waste flow to the Radioactive Liquid
      Waste Treatment Facility at the Los Alamos National Laboratory (LANL) is
      processed before discharge and requires monitoring. Process chromatography is
      used to monitor the trends of contaminants in real time. The purpose of this
      study is to develop an automated on-line IC procedure for the simultaneous
      determination of anions in LANL wastewater.

PMID- 10955512
TI  - Why is solute retention often more erratic for normal-phase separations than
      reversed-phase separations? What can I do to minimize these problems?

PMID- 10955511
TI  - The use of linear expressions of solute boiling point versus retention to
      indicate special interactions with the molecular rings of modified cyclodextrin
      phases in gas chromatography
AB  - The boiling points (degrees C, 1 x 10) of diverse C10 polar solutes from volatile
      oils are set against their relative retention times versus n-undecane to
      calculate linear equations for 12 commercial modified cyclodextrin (CD) capillary
      phases. Ten data points are considered for each CD, then solutes are rejected
      until 5 or more remain that give an expression with a correlation coefficient of
      at least 0.990 and a standard deviation of less than 5.5. Three phases give
      almost perfect correlation, and 3 other CDs have difficulty complying. Solutes
      involved in the equations (most frequently cuminal, linalol, and carvone) are
      presumed to have a 'standard' polar transient interaction with the molecular
      rings of the CDs concerned. Several remaining solutes (mostly citral, fenchone,
      and menthol) exhibit extra retention over the calculated standard (up to 772%),
      which is believed to indicate a firm 'host' CD or 'guest' solute molecular fit in
      some cases. Other solutes show less retention than calculated (mostly
      citronellal, citronellol, estragole, and pulegone). This suggests rejection by
      the CD, which behaves merely as a conventional stationary phase to them. The
      intercept constant in the equation for each phase is suggested to be a numerical
      relative polarity indicator. These b values indicate that 3 hydroxypropyl CDs
      show the most polarity with values from 28 to 43; and CDs that are fully
      substituted with inert groups fall in the range of 15 to 20.

PMID- 10955513
TI  - What is wrong with my splitless injector?

PMID- 10955515
TI  - Topological indices: their nature and mutual relatedness
AB  - We calculated 202 molecular descriptors (topological indices, TIs) for two
      chemical databases (a set of 139 hydrocarbons and another set of 1037 diverse
      chemicals). Variable cluster analysis of these TIs grouped these structures into
      14 clusters for the first set and 18 clusters for the second set. Correspondences
      between the same TIs in the two sets reveal how and why the various classes of
      TIs are mutually related and provide insight into what aspects of chemical
      structure they are expressing.

PMID- 10955514
TI  - Use of statistical and neural net approaches in predicting toxicity of chemicals.
AB  - Hierarchical quantitative structure-activity relationships (H-QSAR) have been
      developed as a new approach in constructing models for estimating
      physicochemical, biomedicinal, and toxicological properties of interest. This
      approach uses increasingly more complex molecular descriptors in a graduated
      approach to model building. In this study, statistical and neural network methods
      have been applied to the development of H-QSAR models for estimating the acute
      aquatic toxicity (LC50) of 69 benzene derivatives to Pimephales promelas (fathead
      minnow). Topostructural, topochemical, geometrical, and quantum chemical indices
      were used as the four levels of the hierarchical method. It is clear from both
      the statistical and neural network models that topostructural indices alone
      cannot adequately model this set of congeneric chemicals. Not surprisingly,
      topochemical indices greatly increase the predictive power of both statistical
      and neural network models. Quantum chemical indices also add significantly to the
      modeling of this set of acute aquatic toxicity data.

PMID- 10955516
TI  - Construction of high-quality structure-property-activity regressions: the boiling
      points of sulfides
AB  - Instead of using the standard molecular descriptors (topological indices) for
      regression analysis, which are numerically fully determined once a molecule is
      selected, we outline the use of variable molecular descriptors that are modified
      during the search for the best regression. The approach is illustrated using
      boiling points of sulfides. We have transformed the connectivity index 1chi into
      a function of two variables (x, y) which differentiate carbon and sulfur atoms.
      The optimal values of the variables (x, y) were determined by minimizing the
      standard error of the regression. With the values x = +0.25 and y = -0.95 for
      carbon and sulfur, respectively, we have obtained a regression based on a single
      descriptor and a standard error of 1.8 degrees C. With elimination of two
      outliers (having a deviation of about 4 degrees C) the standard error is reduced
      to a remarkable 1.3 degrees C.

PMID- 10955517
TI  - Symbolic, neural, and Bayesian machine learning models for predicting
      carcinogenicity of chemical compounds.
AB  - Experimental programs have been underway for several years to determine the
      environmental effects of chemical compounds, mixtures, and the like. Among these
      programs is the National Toxicology Program (NTP) on rodent carcinogenicity.
      Because these experiments are costly and time-consuming, the rate at which test
      articles (i.e., chemicals) can be tested is limited. The ability to predict the
      outcome of the analysis at various points in the process would facilitate
      informed decisions about the allocation of testing resources. To assist human
      experts in organizing an empirical testing regime, and to try to shed light on
      mechanisms of toxicity, we constructed toxicity models using various machine
      learning and data mining methods, both existing and those of our own devising.
      These models took the form of decision trees, rule sets, neural networks, rules
      extracted from trained neural networks, and Bayesian classifiers. As a training
      set, we used recent results from rodent carcinogenicity bioassays conducted by
      the NTP on 226 test articles. We performed 10-way cross-validation on each of our
      models to approximate their expected error rates on unseen data. The data set
      consists of physical-chemical parameters of test articles, alerting chemical
      substructures, salmonella mutagenicity assay results, subchronic histopathology
      data, and information on route, strain, and sex/species for 744 individual
      experiments. These results contribute to the ongoing process of evaluating and
      interpreting the data collected from chemical toxicity studies.

PMID- 10955519
TI  - Complexity of molecules
AB  - Several currently used measures of the complexity of molecules, such as, for
      example, those by Bertz and Randic or those based on the number of spanning
      trees, are briefly reviewed. We also proposed as complexity measures the sum of
      vertex-weights and the sum of edge-weights and their variants related to
      partition of vertex-weights and edge-weights into classes by their numerical
      values. The vertex-weights considered are the squares of the vertex-degrees, and
      the edge-weights are products of vertex-degrees making up the edges. Comparison
      is made between considered complexity measures for selected molecular graphs. All
      considered indices increase with increasing size and cyclicity and most with
      increasing branching. However, they differ regarding the influence of symmetry.

PMID- 10955518
TI  - Simple numerical descriptor for quantifying effect of toxic substances on DNA
      sequences.
AB  - Many chemicals are known to be toxic to living organisms, inducing mutations and
      deletions at the chromosomal and genetic level. One of the tasks in risk
      assessment of genotoxic chemicals is to devise a simple numerical descriptor
      which may be used to quantify the relationship between chemical dose and the
      effect on the genetic sequences. We have developed numerical descriptors to
      characterize different DNA sequences which are especially useful in sequence
      comparisons. These descriptors have been developed from a graphical
      representational technique that enables easy visualization of changes in base
      distributions arising from evolutionary or other effects. In this paper we
      propose a scheme to use these descriptors as a label to help quantify the
      potential risk hazard of chemicals inducing mutations and deletions in DNA
      sequences.

PMID- 10955520
TI  - QSPR modeling: graph connectivity indices versus line graph connectivity indices
AB  - Five QSPR models of alkanes were reinvestigated. Properties considered were
      molecular surface-dependent properties (boiling points and gas chromatographic
      retention indices) and molecular volume-dependent properties (molar volumes and
      molar refractions). The vertex- and edge-connectivity indices were used as
      structural parameters. In each studied case we computed connectivity indices of
      alkane trees and alkane line graphs and searched for the optimum exponent. Models
      based on indices with an optimum exponent and on the standard value of the
      exponent were compared. Thus, for each property we generated six QSPR models
      (four for alkane trees and two for the corresponding line graphs). In all studied
      cases QSPR models based on connectivity indices with optimum exponents have
      better statistical characteristics than the models based on connectivity indices
      with the standard value of the exponent. The comparison between models based on
      vertex- and edge-connectivity indices gave in two cases (molar volumes and molar
      refractions) better models based on edge-connectivity indices and in three cases
      (boiling points for octanes and nonanes and gas chromatographic retention
      indices) better models based on vertex-connectivity indices. Thus, it appears
      that the edge-connectivity index is more appropriate to be used in the structure
      molecular volume properties modeling and the vertex-connectivity index in the
      structure-molecular surface properties modeling. The use of line graphs did not
      improve the predictive power of the connectivity indices. Only in one case
      (boiling points of nonanes) a better model was obtained with the use of line
      graphs.

PMID- 10955521
TI  - Overall connectivities/topological complexities: a new powerful tool for
      QSPR/QSAR
AB  - Earlier attempts to assess the complexity of molecules are analyzed and
      summarized in a number of definitions of general and topological complexity. A
      concept which specifies topological complexity as overall connectivity, and
      generalizes the idea of molecular connectivities of Randic, Kier, and Hall, is
      presented. Two overall connectivity indices, TC and TC1, are defined as the
      connectivity (the sum of the vertex degrees) of all connected subgraphs in the
      molecular graph. The contributions to TC and TC1, which originate from all
      subgraphs having the same number of edges e, form two sets of eth-order overall
      connectivities, eTC and eTC1. The total number of subgraphs K is also analyzed as
      a complexity measure, and the vector of its eth-order components, eK, is examined
      as well. The TC, TC1, and K indices match very well the increase in molecular
      complexity with the increase in the number of atoms and, at a constant number of
      atoms, with the increased degree of branching and cyclicity of the molecular
      skeleton, as well as with the multiplicity of bonds and the presence of
      heteroatoms. The potential of the three sets of eth-order complexities for
      applications to QSPR was tested by the modeling of 10 alkane properties (boiling
      point, critical temperature, critical pressure, critical volume, molar volume,
      molecular refraction, heat of formation, heat of vaporization, heat of
      atomization, and surface tension), in parallel with Kier and Hall's molecular
      connectivity indices (k)chi. The topological complexity indices were shown to
      outperform molecular connectivity indices in 44 out of the 50 pairs of models
      compared, including all models with four and five parameters.

PMID- 10955522
TI  - Base information content in organic formulas
AB  - Three questions are addressed concerning organic formulas at their most primitive
      level: (1) What is the information per atomic symbol? (2) What is the level of
      system redundancy? (3) How are high-information formulas distinguished from low
      information ones? The results are simple yet interesting. Carbon chemistry
      embodies a code which is low in base information and high in redundancy,
      irrespective of database size. Moreover, code units associated with halocarbons,
      proteins, and polynucleotides are especially high in information. Low-information
      units are more often associated with simple alkanes, aromatics, and common
      functional groups. Overall, the work for this paper quantifies the base
      information content in organic formulas; this contributes to research on symbolic
      language, chemical information, and molecular diversity.

PMID- 10955523
TI  - Neural network modeling for estimation of partition coefficient based on atom
      type electrotopological state indices
AB  - A method for predicting log P values for a diverse set of 1870 organic molecules
      has been developed based on atom-type electrotopological-state (E-state) indices
      and neural network modeling. An extended set of E-state indices, which included
      specific indices with a more detailed description of amino, carbonyl, and hydroxy
      groups, was used in the current study. For the training set of 1754 molecules the
      squared correlation coefficient and root-mean-squared error were r2 = 0.90 and
      RMS(LOO) = 0.46, respectively. Structural parameters which included molecular
      weight and 38 atom-type E-state indices were used as the inputs in 39-5-1
      artificial neural networks. The results from multilinear regression analysis were
      r2 = 0.87 and RMS(LOO) = 0.55, respectively. For a test set of 35 nucleosides, 12
      nucleoside bases, 19 drug compounds, and 50 general organic compounds (n = 116)
      not included in the training set, a predictive r2 = 0.94 and RMS = 0.41 were
      calculated by artificial neural networks. The results for the same set by
      multilinear regression were r2 = 0.86 and RMS = 0.72. The improved prediction
      ability of artificial neural networks can be attributed to the nonlinear
      properties of this method that allowed the detection of high-order relationships
      between E-state indices and the n-octanol/water partition coefficient. The
      present approach was found to be an accurate and fast method that can be used for
      the reliable estimation of log P values for even the most complex structures.

PMID- 10955524
TI  - Efficient algorithms to enumerate isomers and diamutamers with more than one type
      of substituent
AB  - In this paper we describe numeric as well as symbolic algorithms for the
      enumeration of substitutional isomers with an unlimited number of different
      achiral substituents. We consider three different scenarios: first, the
      enumeration of diamutamers with a given set of ligand types and ligand
      multiplicity, second, the enumeration of diamutamer libraries with a given ligand
      assortment pattern, and, third, the enumerations of libraries with diamutamers
      exhibiting a limited number of ligands.

PMID- 10955525
TI  - Quantitative structure-property relationships for the prediction of vapor
      pressures of organic compounds from molecular structures
AB  - A quantitative structure-property relationship (QSPR) is developed to relate the
      molecular structures of 420 diverse organic compounds to their vapor pressures at
      25 degrees C expressed as log(vp), where vp is in pascals. The log(vp) values
      range over 8 orders of magnitude from -1.34 to 6.68 log units. The compounds are
      encoded with topological, electronic, geometrical, and hybrid descriptors.
      Statistical and computational neural network (CNN) models are built using subsets
      of the descriptors chosen by simulated annealing and genetic algorithm feature
      selection routines. An 8-descriptor CNN model, which contains only topological
      descriptors, is presented which has a root-mean-square (rms) error of 0.37 log
      unit for a 65-member external prediction set. A 10-descriptor CNN model
      containing a larger selection of descriptor types gives an improved rms error of
      0.33 log unit for the external prediction set.

PMID- 10955526
TI  - Data evaluation in high-performance liquid chromatography-diode-array detection
      fluorescence detection by information theory
AB  - The concepts of information theory were applied to the high-performance liquid
      chromatography (HPLC) technique, with diode-array (DAD) and/or fluorescence (FLD)
      detections. The information amount for a complete analysis can be computed as a
      function of analytical parameters, such as the number of analytes, level of
      concentration, and standard deviation of determinations. By means of the proposed
      method, the information content of a qualitative and quantitative analysis
      accomplished by HPLC-DAD-FLD was estimated, and sensitivity was optimized taking
      into account a maximum information content, while the detection limit was
      estimated considering that at this level of concentration the information content
      approaches zero.

PMID- 10955528
TI  - Analysis of the flow patterns of liquid organic compounds between blade
      electrodes by classification models
AB  - The flow patterns of 20 organic liquids with diverse structures and
      functionalities between electrodes were measured under a dc electric field. The
      results clearly showed the existence of a strong relationship between the flow
      pattern of a compound and its molecular structure. On the basis of a variety of
      23 molecular descriptors including those obtained by quantum-chemical
      calculations, multiple regression analysis and discriminant analysis were applied
      to identify the significant factors contributing to the flow patterns. For the
      flow rate dipole moment, nucleophilic delocalizability and lipophilicity as
      expressed by the 1-octanol/water partition coefficient were found to be the key
      factors as judged by a five-value regression model with a squared correlation
      coefficient (r2) of 0.881. For the direction of the flow, just two quantum
      chemical parameters, namely, absolute hardness and the self-polarizability
      normalized by molecular volume, were identified as significant factors by using
      linear discriminant analysis. The numbers of misclassified compounds were only
      one and two for training and prediction (leave-one-out cross-validation),
      respectively, by the best discriminant model.

PMID- 10955529
TI  - Quantitative structure-activity relationship of flavonoid analogues. 3.
      Inhibition of p56lck protein tyrosine kinase.
AB  - Quantitative structure-activity relationship (QSAR) studies on 104 flavonoid
      derivatives as p56lck protein tyrosine kinase (PTK) inhibitors were performed,
      using a large number of molecular descriptors calculated by CODESSA software.
      Multiple linear regression and orthogonalization of descriptors were applied to
      generate models for the prediction of biological activities for binding
      flavonoids to PTK. The obtained results demonstrate in detail the importance of
      electrostatic and quantum chemical descriptors for the interaction of flavonoids
      with the specific p56lck enzymatic active site environment. In particular, the
      maximal total interaction for a C-O bond is the most important factor in
      regression. Use of orthogonalization in regression models provides a valuable
      improvement for the interpretative and predictive capacity of structure-activity
      relationships found.

PMID- 10955527
TI  - Heterogeneous catalyst design using stochastic optimization algorithms
AB  - We describe the application of two stochastic optimization algorithms to
      heterogeneous catalyst design. In particular, we discuss the optimal design of a
      two-component catalyst for the diffusion limited A + B --> 0 and A + B2 --> 0
      reactions in which each of the reactants are adsorbed specifically on one of the
      two distinct catalytic sites. The geometric arrangement of the catalytic sites
      that maximizes the catalyst activity is determined by the use of a genetic
      algorithm and a simulated annealing algorithm. In the case of the A + B --> 0
      reaction, it is found that the catalyst surface with the optimal active site
      distribution, that of a checkerboard, is approximately 25% more active than a
      random site distribution. A similar increase in catalytic activity is obtained
      for the A + B2 --> 0 reaction. While both the genetic and simulated annealing
      algorithms obtain identical optimal solutions for a given reaction, the simulated
      annealing algorithm is shown to be more efficient.

PMID- 10955531
TI  - On molecular polarizability: 3. Relationship to the ionization potential of
      haloalkanes, amines, alcohols, and ethers
AB  - The relationship between the ionization potential and the parameters molecular
      electronegativity and molecular polarizability for haloalkanes, amines, alcohols,
      and ethers was investigated. There is no good linear correlation between the
      ionization potential Ip and molecular electronegativity chi(eq) alone for these
      compounds. Ip can be modeled well with three parameters: chi(eq), polarizability
      effect index (PEI) of an alkyl group, and atomic polarizability (P). Further, a
      single expression for predicting the Ip values of aldehydes, esters, nitriles,
      and carboxylic acids was developed: Ip(Rz)(eV) = Ip(MeZ) + 1.4544delta chi(eq) -
      1.6435delta sigmaPEI(Ri). Here Ip(MeZ) is the experimental ionization potential
      of monosubstituted methane MeZ. Delta chi(eq) and delta sigmaPEI(Ri) are the
      difference in the molecular electronegativity and the difference in the
      polarizability effect index of alkyl groups attached to the functional group Z
      between molecules MeZ and RZ, respectively.

PMID- 10955532
TI  - Ring perception: proof of a formula calculating the number of the smallest rings
      in connected graphs
AB  - A general mathematical proof of a formula proposed and used by Fan et al. for
      calculating the number of the smallest rings in their smallest set of the
      smallest rings search algorithm is reported. This proof generalizes this formula
      to all connected cyclic graphs.

PMID- 10955530
TI  - Three-dimensional quantitative structure-activity relationship analysis of the
      new potent sulfonylureas using comparative molecular similarity indices analysis.
AB  - The present study describes the implementation of a new three-dimensional
      quantitative structure-activity relationship (3D-QSAR) technique: comparative
      molecular similarity indices analysis (CoMSIA) to a set of novel herbicidal
      sulfonylureas targeted acetolactate synthase. Field expressions in terms of
      similarity indices in CoMSIA were applied instead of the usually used Lennard
      Jones and Coulomb-type potentials in CoMFA. Two different kinds of alignment
      techniques including field-fit alignment and atom-by-atom fits were used to
      produce the molecular aggregate. The results indicated that those two alignment
      rules generated comparative 3D-QSAR models with similar statistical significance.
      However, from the predictive ability of the test set, the models from the
      alignment after maximal steric and electrostatic optimization were slightly
      better than those from the simple atom-by-atom fits. Moreover, systematic
      variations of some parameters in CoMSIA were performed to search the best 3D-QSAR
      model. A significant cross-validated q2 was obtained, indicating the predictive
      potential of the model for the untested compounds; meanwhile the predicted
      biological activities of the five compounds in the test set were in good
      agreement with the experimental values. The CoMSIA coefficient contour plots
      identified several key features explaining the wide range of activities, which
      were very valuable for us in tracing the properties that really matter and
      getting insight into the potential mechanisms of the intermolecular interactions
      between inhibitor and receptor, especially with respect to the design of new
      compounds.

PMID- 10955533
TI  - Measuring splitting and overlapping in molecular systems. A fuzzy set estimation
      of reaction hazards
AB  - An algorithm for assessments of fuzzy molecular structural characteristics has
      been presented, and its chemical relevance is approved for numerous evidences of
      reaction mechanisms. Empirical rules pervading the results of chemical synthesis
      are continuously the source of information efficiently used by experimental
      chemists and technologists. Approaching them theoretically to broaden areas of
      applicability and to make them more precise for better prediction is of great
      importance to reach progress in the chemical information recognition and to steer
      and control technological processes. Fuzzy sets called splitting and overlapping
      have been applied for assessments of the reaction hazards. The mathematically
      grounded properties turned out to underlie well-known empirical rules for
      preliminary estimations of organic reaction tendencies. Informative quantitative
      data shown are revealing new ways of understanding basic chemical reaction
      mechanisms.

PMID- 10955534
TI  - Ultrafast algorithm for designing focused combinational arrays
AB  - A novel greedy algorithm for the design of focused combinatorial arrays is
      presented. The method is applicable when the objective function is decomposable
      to individual molecular contributions and makes use of a heuristic that allows
      the independent evaluation and ranking of candidate reagents in each variation
      site in the combinatorial library. The algorithm is extremely fast and convergent
      and produces solutions that are comparable to and often better than those derived
      from the substantially more elaborate and computationally intensive stochastic
      sampling techniques. Typical examples of design objectives that are amendable to
      this approach include maximum similarity to a known lead (or set of leads),
      maximum predicted activity according to some structure-activity or receptor
      binding model, containment within certain molecular property bounds, and many
      others.

PMID- 10955536
TI  - QM/NN QSPR models with error estimation: vapor pressure and logP
AB  - QSPR models for logP and vapor pressures of organic compounds based on neural net
      interpretation of descriptors derived from quantum mechanical (semiempirical MO;
      AM1) calculations are presented. The models are cross-validated by dividing the
      compound set into several equal portions and training several individual
      multilayer feedforward neural nets (trained by the back-propagation of errors
      algorithm), each with a different portion as test set. The results of these nets
      are combined to give a mean predicted property value and a standard deviation.
      The performance of two models, for logP and the vapor pressure at room
      temperature, is analyzed, and the reliability of the predictions is tested.

PMID- 10955535
TI  - Study of the action of flavonoids on xanthine-oxidase by molecular topology.
AB  - A study was performed on xanthine-oxidase inhibition by 22 flavonoids, including
      flavones, flavonols, flavanones, and chalcones, using UV spectroscopy for
      experimental data and molecular topology to establish the structure-activity
      relationship (SAR) model. The flavonoids were classified into four groups
      according to their activity on xanthine-oxidase (inactive, low, significant, or
      high), and linear discriminant analysis was used to classify each compound within
      a group. The results led to a very good model, which was able to classify
      correctly as xanthine oxidase inhibitors, along with a test set of molecules
      including a variety of different compounds such as allopurinol, caffeic acid,
      esculetin, and alloxantin.

PMID- 10955537
TI  - Structural analysis of transition metal beta-X substituent interactions. Toward
      the use of soft computing methods for catalyst modeling
AB  - Fuzzy logic and neural network techniques are used to classify intramolecular
      interactions between transition metals (M) and beta-X substituents in the
      following structural motif (LnMC(alpha)(A1)(A2)-C(beta)(B1)(B2)X). These
      interactions are relevant to the direct polymerization of functionalized olefins
      by Ziegler-Natta (ZN) catalysis. The efficiency and effectiveness of different
      soft computing techniques are compared. These methods give not only encouraging
      results with respect to general data mining issues but also insight into the
      factors that effect interactions between transition metals and beta-X
      substituents.

PMID- 10955538
TI  - Quantitative relationship between rate constants of the gas-phase homolysis of C
      X bonds and molecular descriptors
AB  - A quantitative structure-property relationship (QSPR) study on the kinetic
      parameters of the gas-phase homolysis for 287 different C-X bonds was carried out
      using the CODESSA program. Successful five-, four-, and three-parameter models
      were developed for the prediction of the log k (891 K) values. These respective
      multiple linear correlations were obtained by automatic selection of appropriate
      molecular descriptors for reagents and products, using only the information
      encoded in the chemical structure.

PMID- 10955539
TI  - Comment on "Response to the comment on exhaustive generation of organic isomers.
      5. Unsaturated optical and geometrical stereoisomers and a new CIP subrule"

PMID- 10955540
TI  - Augmented Hummelsheim procedure for paralytic strabismus.
AB  - PURPOSE: To report a modification of the Hummelsheim procedure for use in the
      management of paralytic strabismus. METHODS: Eight patients with paralytic
      strabismus secondary to third nerve palsy (n=1), sixth nerve palsy (n=3),
      combined cranial nerve palsy (n=1), or extraocular muscle damage (n=3) were
      treated using a modification of the Hummelsheim transposition procedure. The
      procedure involves half-tendon transpositions of the adjacent rectus muscles to
      the insertion of the paralyzed muscle, coupled with resection of the transposed
      halves. Further augmentation was achieved by surgical or pharmacologic weakening
      of the ipsilateral (n=6) or contralateral (n=1) antagonist. One patient underwent
      the procedure bilaterally. All patients underwent at least 6 weeks of follow-up.
      RESULTS: The mean preoperative primary position deviation in the seven unilateral
      cases was 54 prism diopters (delta) (range: 25-85 delta). Preoperative forced
      ductions were positive in four cases. Resections varied from 4-8 mm. Ipsilateral
      antagonist recession varied from 0-14 mm. The mean change was 52 delta (range: 25
      85 delta). Five cases were aligned within 15 delta of orthotropia at 6 weeks. No
      cases of anterior segment ischemia or induced vertical deviation were noted.
      CONCLUSION: The modified Hummelsheim procedure appears capable of correcting
      large angles of strabismus associated with muscle palsy of various etiologies. It
      is safe, amenable to adjustable sutures, and relatively tissue- and vessel
      sparing. Additional study is required to understand more fully the procedure's
      component effects and its interaction with ocular rotation.

PMID- 10955542
TI  - Intraocular lens implantation in Marfan's syndrome.
AB  - PURPOSE: To describe the results of the removal of ectopic lenses from patients
      with Marfan's syndrome using the scleral fixation method. METHODS: Intraocular
      lenses (IOLs) were implanted in six eyes affected by lens dislocation (ectopia
      lentis) using either the scleral fixation method (five eyes) or a silicone IOL in
      the capsular bag (one eye). Mean patient age ranged from 8-11 years and follow-up
      ranged from 7-20 months. RESULTS: Functional success was obtained in all eyes.
      Postoperative visual acuity was 20/20 to 20/40. One patient showed a dislocation
      of the IOL in the anterior chamber. In three eyes, an opacification of the
      posterior capsule was treated using an Nd:YAG laser. CONCLUSION: Intraocular lens
      implantation using the scleral fixation technique is the first choice in patients
      with Marfan's syndrome because it reduces the complications of IOL decentration.

PMID- 10955541
TI  - Botulinum treatment of infantile esotropia with abduction nystagmus.
AB  - PURPOSE: To examine the effect of botulinum toxin type A (BTA) on the final
      correction of esotropia, A and V patterns, overaction of the oblique muscles, and
      dissociated vertical deviation (DVD) in infantile esotropia with nystagmus in
      abduction. METHODS: This retrospective study examined 54 patients treated with
      simultaneous bilateral medial injection of BTA. Subjects were divided into two
      groups: group 1 (first injection <18 months of age) and group 2 (first injection
      >18 months of age). RESULTS: Pre-BTA, group 1 patients had an angle of esotropia
      noticeably higher and fewer A patterns than group 2 patients. Post-BTA, group 2
      received significantly fewer injections of BTA than group 1. The magnitude of the
      A patterns improved. Prior frequency of DVD increased significantly in group 1
      (100%): 79% of DVD was decompensated compared with 47% in group 2. Overall
      success was obtained in 14% and 58% of groups 1 and 2, respectively. CONCLUSION:
      We do not support BTA treatment in infantile esotropia with nystagmus in
      abduction prior to age 18 months. After 18 months, the horizontal results are
      excellent and neither the incidence nor the degree of previous DVD are
      decompensated, resulting in high success rates for overall deviation and
      improving anisotropy in A.

PMID- 10955543
TI  - Borish Vectographic Nearpoint Card II contour and random dot stereoacuity in
      children.
AB  - PURPOSE: To determine the completion rate and normative values for the Borish
      Vectographic Nearpoint Card II (Stereo Optical Co, Inc, Chicago, III) contour and
      random dot stereoacuity tests in children. METHODS: Children had to pass a
      modified clinical screening technique to be included in the study to eliminate
      vision problems that could potentially affect stereoacuity. One hundred forty-six
      children in second through fourth grade (mean age: 8.27 years) from a middle
      class, suburban, primarily white, elementary school near Columbus, Ohio
      participated in this investigation. Random dot and contour stereoacuity were
      measured using the Borish Vectographic Nearpoint Card II. RESULTS: All of the
      children were able to identify which circle had disparity on the 1280 seconds of
      arc contour stereoacuity target, but six children were unable to perceive the "E"
      on the 1280 seconds of arc random dot target. The median stereoacuity was 80
      seconds of arc on both the contour and random dot stereotests in this population.
      CONCLUSION: A high completion rate was found on both the contour and random dot
      stereoacuity tests. Median stereoacuities were higher on the Borish Vectographic
      Nearpoint Card II in this population than those previously reported with the
      Randot contour stereoacuity test and Randot Preschool random dot stereoacuity
      test in children.

PMID- 10955544
TI  - The effects of experimentally induced anisometropia on stereopsis.
AB  - PURPOSE: To determine the effects of experimentally induced anisometropia on
      stereopsis in healthy adults to assess the potentially detrimental effects of
      uncorrected anisometropia on the development of stereoacuity during childhood.
      METHODS: Twenty-one healthy adult volunteers ranging in age from 22-34 years
      (mean: 27 years) and free of ocular disease participated in the study. Four
      different types of anisometropia (unilateral myopia, unilateral hyperopia, or
      unilateral astigmatism [90 degrees or 45 degrees]) were induced in random order
      by placing trial lenses over the right eye in 1 diopter (D) increments ranging
      from 1-3 D. Stereoacuity was measured using the Titmus stereotest with patients
      placing the cross-polarizing stereoacuity glasses over their lenses or trial
      frames. RESULTS: Stereoacuity levels were reduced in proportion to the degree of
      anisometropia in all patients. One diopter of spherical anisometropia reduced
      stereoacuity to an average 57-59 arc seconds; 1 D of cylindrical anisometropia
      reduced stereoacuity to an average 51-56 arc seconds. Three diopters of
      anisometropia, regardless of type, produced a marked reduction of stereoacuity in
      all patients. CONCLUSIONS: Low levels of anisometropia, both spherical and
      astigmatic, can have potentially significant adverse effects on high-grade
      binocular interaction in adults. Foveal suppression, which is directly related to
      the degree of anisometropia, may be responsible for the loss of stereopsis. The
      data suggest the effects of anisometropia on stereopsis should be considered in
      the empiric correction of anisometropic refractive errors in children.

PMID- 10955545
TI  - Clinical symptoms and visual outcome in patients with presumed congenital
      cataract.
AB  - PURPOSE: To investigate clinical symptoms and visual outcome in patients who had
      presumed congenital cataract with visual acuity > or =20/200. METHODS: Twenty
      nine patients (50 eyes) ranging in age from 5-28 years were included in this
      study. Congenital cataract was diagnosed by patients' past history, previous
      medical records, and typical findings of congenital cataract. Inclusion criteria
      were patients with visual acuity measured by Snellen chart, best corrected visual
      acuity > or =20/200, and no eye or systemic diseases influencing visual acuity.
      Seven patients had unilateral cataracts and 22 patients had bilateral cataracts.
      Cataracts were nuclear in 29 eyes, anterior or posterior subcapsular in 12 eyes,
      and polar in 7 eyes. All patients underwent lens aspiration or
      phacoemulsification combined with posterior chamber intraocular lens (PC-IOL)
      implantation without performing intentional posterior capsulotomy and anterior
      vitrectomy. RESULTS: The most common clinical symptom was visual disturbance
      followed by blurred vision, glare and knitting the brow, strabismus, and
      leukocoria. Comparison of calculated PC-IOL power showed a more significant
      myopic shift in unilateral cataract than in bilateral cataract. Postoperative
      best corrected visual acuity >20/25 was attained in 28 (65.1%) eyes with
      bilateral cataracts and 1 (14.3%) eye with a unilateral cataract. CONCLUSIONS:
      Cataract surgery is effective not only in improving visual acuity but also in
      eliminating clinical symptoms. Delaying cataract surgery in early infancy should
      be considered to avoid intentional operative procedures in patients with
      bilateral congenital cataract preserving visual acuity >20/200.

PMID- 10955546
TI  - Infantile esotropia.

PMID- 10955547
TI  - Probable poststreptococcal anterior uveitis in a 3-year-old boy.

PMID- 10955548
TI  - Bilateral orbital involvement as a presenting sign in a child with acute
      lymphoblastic leukemia.

PMID- 10955549
TI  - A large ethmoido-orbital osteoma presenting with epiphora in an 11-year-old boy.

PMID- 10955550
TI  - Isolated oculomotor nerve palsy with pupillary abnormality in systemic lupus
      erythematosus.

PMID- 10955551
TI  - B-cell lymphoma presenting as a periorbital mass in a child.

PMID- 10955552
TI  - Defecation problems in children with Hirschsprung's disease: a biopsychosocial
      approach.
AB  - Although most patients with operated Hirschsprung's disease (HD) have good
      continence in adulthood, a majority have postoperative defection problems during
      school age. Persistence of chronic constipation and/or incontinence may have
      considerable consequences for psychosocial development, parent-child
      interactions, quality of life, and the child's general condition. Considering
      these consequences, it is important to treat these problems as early as possible.
      From a biopsychosocial view, we developed a multidisciplinary treatment aimed at
      resolving defecation problems by teaching the child bowel self-control, primarily
      by training optimal defecation skills and subsequently toilet behavior. This
      treatment, carried out by a child psychologist, a pediatric physiotherapist, and
      a pediatric surgeon, consists of five steps: explanation; extinction of fear and
      avoidance behavior; learning new defecation behavior; learning an adequate
      straining technique; and generalization toward daily life. The effect of the
      treatment was investigated retrospectively in 16 boys with operated HD. The
      children improved significantly in all aspects during treatment, suggesting that
      multidisciplinary treatment can significantly reduce the postoperative chronic
      bowel problems of most children with operated HD. The treatment was as effective
      in young children (2-5 years) as in older children (5-14 years).

PMID- 10955553
TI  - Biopsychosocial treatment of defecation problems in children with anal atresia: a
      retrospective study.
AB  - In a retrospective study, we examined whether multidisciplinary treatment based
      on a biopsychosocial approach and carried out by a pediatric surgeon, a child
      psychologist, and a pediatric physiotherapist is successful in reducing
      defecation problems (incontinence and/or constipation) in children with operated
      anal atresia (AA) (mean age 6.9 +/- 4.01 years). A second question was whether
      this treatment is successful in young children aged 2-5 years. The
      multidisciplinary approach consisted of standard medical treatment and a
      behavioral program to teach children and their parents adequate defecation
      behavior including an adequate straining technique. Forty-three children aged 2
      16 years were included: 27 boys and 16 girls with AA, of whom 26 had high or
      intermediate and 17 low AA. Besides continence and constipation, defecation
      behavior and straining technique were evaluated. The children improved
      significantly during treatment in all aspects of defecation. No differences in
      effect of treatment were found between young children (2-5 years) and older ones,
      so this treatment seems to be equally effective in both age groups. This study
      demonstrates that both somatic and behavioral factors contribute to the
      persistence of chronic defecation problems. It is concluded that treatment of
      these problems in patients with operated AA should include behavioral
      modification techniques.

PMID- 10955554
TI  - Cineradiographic evaluation of postoperative patients with esophageal atresia and
      tracheoesophageal fistula.
AB  - Esophageal dysmotility is a common occurrence after successful repair of
      esophageal atresia (EA) and tracheoesophageal fistula (TEF). The etiology of this
      motility disorder, however, remains controversial. Cine-barium esophagograms were
      performed in 25 survivors of EA/TEF at a mean age of 30.5 months. A clinical
      evaluation was done at the same time and the results were classified as
      "excellent", "good", and "fair". The study revealed that 88% of patients had
      dysmotile esophageal segments and segmental contractions. Normal peristalsis was
      seen in only 16% of patients and 64% showed to-and-fro movements. The bolus
      transit time was delayed in 60%. The clinical status of these patients correlated
      well with the cine-radiographic findings. Thus, abnormal motility of the
      esophagus, which may be inherent, exists in postoperative survivors of EA/TEF and
      may be responsible for the clinical status of these patients.

PMID- 10955555
TI  - Intestinal bypass of the oesophagus: 117 patients in 28 years.
AB  - This study includes 117 patients operated upon in the period from 1970 to 1999.
      Indications, surgical techniques, complications, and results are reviewed.
      Indications included: long-gap oesophageal atresia with or without fistula in 81
      patients; peptic stenosis in 19; caustic stenosis in 12; oesophageal varices in
      2; and 1 case each of oesophageal epidermolysis bullosa, total oesophageal
      leiomyomatosis, and a non-functioning antiperistaltic retrosternal colic graft
      operated upon in another hospital. A retrosternal bypass was performed 106 times:
      98 first operations and 8 redos; the intrathoracic technique was used 19 times.
      The left transverse colon was used in 107 cases (85.6%), the right transverse
      colon in 8 (6.4%), and the ileocecum in 10 (8%). All the intestinal bypasses were
      placed in the isoperistaltic direction. There were 5 deaths in the first 11 years
      of our experience; no patient died from 1982 on. Ten complications were treated
      conservatively (8%): 2 wound infections healed with medical treatment, and 8
      leaks of the cervical anastomosis closed spontaneously. The major surgical
      complications were 8 gangrenous bypasses (6.4%), removed and reoperated about 1
      year later utilizing an ileocolic retrosternal graft. Three cases of peptic
      disease of the colic bypass (2.4%) were successfully treated with the author's
      technique. Nine patients had minor surgical complications (7.2%): 3 strictures of
      the oesophagocolic anastomosis in a retrosternal bypass (resected and reoperated)
      and 6 cases of adhesive occlusion. In our opinion, the best substitute of the
      oesophagus is the colon, particularly the left transverse segment, which may be
      placed behind the sternum or in the oesophageal bed, always in the isoperistaltic
      direction. The low mortality (4%), restricted to the early period of our
      experience, and few major surgical complications (6.4%) are acceptable
      considering the importance of the operation, and the long-term results may be
      considered very satisfactory.

PMID- 10955556
TI  - Gastric teratoma in children.
AB  - Gastric teratoma (GT) comprises less than 1% of all teratomas in children. Though
      GT in the presence of immature neuroepithelial elements is regarded as malignant,
      the prognosis is excellent after complete excision of the tumor. Because of its
      rarity the world literature lacks a large study. Clinical experience with ten
      cases of GT is presented and discussed. Only one patient was female; the mean age
      at presentation was 3.2 months. Two cases were immature grade III GT; one of
      these had infiltrated the left lobe of the liver and the transverse colon while
      the other had metastasized to the regional lymph nodes and omentum. All the
      patients underwent complete excision. There were no deaths, and after a mean
      follow-up period of 4.2 years, all the patients had no recurrence and were
      healthy. Both the mature and immature types of GT have an excellent prognosis
      after complete excision of the tumor. Even when the immature type infiltrates
      surrounding structures, complete excision offers recurrence-free survival without
      requiring chemo- or radiotherapy.

PMID- 10955557
TI  - Head and neck teratomas in children.
AB  - A retrospective review of seven patients with teratomas of the head and neck
      treated at out center over the past 5 years, which represented 2% of all
      teratomas (sacrococcygeal, ovarian, and retroperitoneal) seen over the past 20
      years, was performed. After investigation to exclude associated anomalies, all
      but one of the children underwent surgery for removal of the tumour. All excised
      tumours were subjected to histopathological examination to confirm their
      teratomatous nature. The patients were followed up at regular intervals for up to
      4 years. The patients' ages ranged from newborn to 2.5 years. There were three
      cervical, two oral, and two skull teratomas. The youngest patient had a cervical
      teratoma with respiratory compromise, requiring tracheal intubation. All but one
      patient (skull teratoma) had excision of the tumours with a satisfactory outcome.
      Histopathological examination of the excised tumours showed mature tissue from
      the three germinal layers in all specimens. Specific components included
      glandular epithelium, keratinising epithelium, and muscle fibres. Follow-up did
      not show any recurrence in the operated children. The three with cervical
      teratomas had normal levels of thyroid hormone postoperatively. Head and neck
      teratomas in children are mostly benign lesions amenable to curative excision. In
      cervical teratomas airway management takes priority.

PMID- 10955558
TI  - Circumumbilical pyloromyotomy: larger pyloric tumours need an extended incision.
AB  - Circumumbilical pyloromyotomy has been used widely to offer an optimum cosmetic
      approach. On occasion, there are difficulties in delivering the large pyloric
      tumour through a relatively small incision. The authors prospectively collected a
      series of 39 consecutive pyloromyotomies performed over a period of 3 years in
      three teaching hospitals. Patients were aged 13 to 90 days (average 35) and the
      male-female ratio was 5:1. The initial operative approach was a right upper
      quadrant (RUQ) incision (n = 6) and later a circumumbilical incision (CUI), with
      or without lateral extension, combined with transverse division of the linea alba
      and part of both rectus muscles (n = 33). Two infants (1 RUQ and 1 CUI) developed
      wound infections, which were treated with antibiotics. There were no other peri-
      or postoperative complications. It was necessary to extend the incision in one
      third of CUI cases (n = 12) in order to facilitate the delivery of a large
      pyloric tumour through the incision. Both omega-shaped (n = 3) and a new modified
      extension (n = 9) have been used with good cosmetic results.

PMID- 10955560
TI  - Ultrasound-guided percutaneous sclerotherapy of hydatid liver cysts in children.
AB  - To evaluate the efficacy of ultrasound (US) guided percutaneous sclerotherapy in
      the pediatric population, 14 hydatid liver cysts (HLC) in eight male patients
      whose ages ranged between 6 and 16 years (mean 9.9 years) were treated. The
      maximum diameter was 110 mm. Albendazole was administered orally to all patients
      for 1 week before percutaneous treatment and for 3-6 months after the procedure
      to prevent dissemination of the disease. Cyst puncture was performed with 20 G
      Chiba needles using US guidance. More than one-half of the estimated cyst volume
      was aspirated, then 20% hypertonic saline (7 cysts) or sterile 96% alcohol (7
      cysts) equivalent to one-third of the estimated cyst volume was injected into the
      cavity and left for 5-15 min. Finally, all the fluid in the cavity was
      reaspirated. Catheterization was not performed. Follow-up US examinations were
      performed every month during the first 6 months and every 3 months thereafter.
      The follow-up period ranged between 6 and 51 months (mean 15 months). No major
      complications were seen during or after the procedures. Two cysts in two patients
      completely disappeared. Volumes of the 11 cysts in five patients who were
      followed for 6-21 months were markedly reduced (22%-64% of the initial volume)
      and thick septations and solid debris-like structures were seen within the cyst
      cavities. There was no significant change in 1 cyst. US-guided percutaneous
      sclerotherapy is thus a safe and effective treatment of HLC in children.

PMID- 10955559
TI  - Congenital duodenal obstruction: early antenatal ultrasound diagnosis.
AB  - Twenty-nine patients with congenital duodenal obstruction (DO) detected as a
      "double bubble" (DB) on antenatal ultrasound (US) or diagnosed postnatally were
      seen at the Women's and Children's Hospital between 1985 and 1994; 24 (83%) had
      antenatal scans, with 21 (87%) DBs visualised. The 3 fetuses with normal scans
      who developed DO postnatally had duodenal "windsocks". Five of the 24 scanned
      patients (21%) were found to have a DB before 20 weeks' gestation: 1 simple
      duodenal atresia, 2 duodenal atresias with chromosomal abnormalities (1 trisomy
      21 and 1 triploidy), 1 biliary atresia with a pre-pyloric vein, and 1
      malrotation. Sixteen (67%) cases were detected with scans after 20 weeks (range
      28-36 weeks); 12 (75%) of these were done for polyhydramnios. In response to a
      questionnaire to 9 of the 16 parents whose fetuses underwent a late scan, 5 had
      had normal early scans elsewhere and 4 did not respond (4 of the remaining 7 had
      died and 3 were lost to follow-up). Eleven of the 29 patients (38%) had abnormal
      karyotypes, and 4 (22%) of the 18 with a normal karyotype had associated
      anomalies. Two sets of familial cases were noted. Early antenatal diagnosis of DO
      is possible in a minority of cases, and this early diagnosis may be associated
      with an increased risk of other pathology. Furthermore, early demonstration of a
      DB at routine US prior to 20 weeks allows appropriate counseling and the option
      of mid-trimester termination, whereas this is more difficult later in the
      pregnancy. In all cases detected antenatally, planning of delivery and parent
      counseling should be achieved.

PMID- 10955561
TI  - Prognosis of extrahepatic bile-duct atresia after hepatoportoenterostomy.
AB  - Clinical and histologic findings from 206 patients operated upon for extrahepatic
      biliary atresia (EHBA) are analyzed in order to define the prognosis of patients
      with EHBA. The prospective study took into consideration both initial fibrosis of
      the liver and the morphology of the porta hepatis (PH) at surgery. Kaplan-Meier
      survival estimates and statistical calculations demonstrated a relationship
      between long-term survival and histologic findings in the liver and porta
      hepatis. The efficacy of HPE is significantly influenced by the morphology of the
      PH and to a lesser extent by the initial liver fibrosis. Surgery should thus
      achieve pattern 1 morphology of the PH, but this is problematic because of the
      close relationship of the vascular and biliary structures in its two lateral
      zones.

PMID- 10955562
TI  - Successful use of the "patch, drain, and wait" laparotomy approach to perforated
      necrotizing enterocolitis: is hypoxia-triggered "good angiogenesis" involved?
AB  - The traditional and most frequently employed surgical approach to perforated
      necrotizing enterocolitis (NEC), laparotomy and bowel resection with enterostomy
      creation, has been associated with an unacceptably high mortality and major
      morbidity (sepsis, short-gut syndrome, strictures, long-term total parenteral
      nutrition (TPN), prolonged and costly hospitalizations with multiple operations,
      the inevitable open-and-close procedure for "hopeless" extensive gut ischemia in
      approximately 10% of laparotomy cases, etc.). The use of the laparotomy "patch,
      drain, and wait" (PD&W) approach to this serious of NEC complication has provided
      a simple, direct, and effective means of dealing with this problem. The basic
      principle is to resect no gut and do no enterostomies. The details are presented
      here as well as the multiple types of "patching" and the importance of use of
      extensive direct-vision draining with bilateral small Penrose drains from the
      undersurfaces of both diaphragms into the pelvis with exit sites in both lower
      quadrants. Proper and effective patching and draining cannot be done blindly,but
      requires direct vision (laparotomy or laparoscopy). The critical components and
      timing of the "waiting" are emphasized, including the vital importance of strict
      avoidance of early post-drainage laparotomy in the 7- to 14-day post-drainage
      period (whether the drainage is percutaneous, laparotomy PD&W, or laparoscopy
      PD&W) due to the early, life-threatening-ending hypervascularity that occurs at
      this time and if left unmolested will function beneficially as life- and gut
      saving "good angiogenesis". The bilateral Penrose drains capture fecal fistulas
      and function quite well as de-facto enterostomies as the peritoneal cavity is
      rapidly obliterated by adhesions and massive, florid hypervascularity/gut hypoxia
      triggered "good angiogenesis" (no peritoneal cavity, no peritonitis). Broad
      spectrum triple antibiotics and the routine use of TPN contribute to favorable
      results. The lessons/experiments of nature encountered in newborns with midgut
      atresia(s) and remarkable levels of gut survival, in the occasional case with
      only meconium peritonitis and no obstruction ("auto-anastomosis") are pertinent
      here as the TPN of PD&W is provided in atresia(s) by the maternal-placental
      circulation and the sterile peritoneal cavity of atresia(s) is simulated by the
      combination of antibiotics and peritoneal-cavity obliteration. Life- and gut
      saving "good angiogenesis" is common to both situations. A 15-year personal
      experience with the PD&W laparotomy approach to perforated NEC in 23 cases is
      reported here with no mortality in the initial 60 postoperative days, no major
      morbidity, and no second operation required in 70% (spontaneous "auto
      anastomosis") of cases. All infants with extensive gut ischemia/necrosis (NEC
      totalis) who would otherwise be classified as "hopeless" and managed by open-and
      close only were managed in this experience successfully by PD&W with preservation
      of both life and an adequate amount of gut, although a second operation was
      required in these cases to re-establish intestinal continuity. A particularly
      striking observation was the rapid transition of these infants from profound
      illness to near-normalcy in a matter of hours after the initiation of PD&W--much
      like the rapid clinical changes accompanying the lancing of a boil or an abscess.
      An involvement of hypoxia-induced "good angiogenesis" with marked
      hypervascularity and involving molecules, genes, and receptors of the vascular
      endothelial growth factor family of hypoxia-induced angiogenesis molecules is
      speculated upon, and clinical studies to document these speculations are
      suggested as well as studies evaluating the potential of laparoscopic PD&W. The
      usefulness of Argyle chest-tube "venting" and "stenting" by trans-anal passage
      above colonic "patched" areas as seen in 2 cases is worthy of further study and
      use.

PMID- 10955563
TI  - Fetal intestinal graft is the best source for intestinal transplantation.
AB  - Adult intestinal allografts have demonstrated high immunogenicity in human
      transplantation, making the search for new and more favorable grafts an actual
      problem. Accepting that fetal and newborn immune systems are relatively immature,
      their intestines could be ideal sources for organ donation. The purpose of this
      study was to compare the immunogenicity of fetal, newborn, and adult intestine
      for selection of the least antigenic. Using a bidirectional rat model for
      immunologic responses, 116 small-bowel transplantations were done: 36 fetal, 40
      newborn, and 40 adult grafts. Two histocompatibility barriers and different
      immunosuppression regimes were used. For fetal and newborn intestines, free
      grafts into the omentum of adult recipients were done; for adult intestines,
      accessory grafts in adult recipients of the same age, using vascular anastomoses.
      The diagnosis of graft rejection and graft-versus-host disease (GVHD) was based
      on histology of hematoxylin and eosin-stained biopsies from target organs.
      Recipients of fetal and newborn grafts did not show signs of GVHD, while 12% of
      the adult group did (P < 0.05). Rejection was less severe in fetal and adult (P >
      0.05) than in newborn (P < 0.05) intestinal transplantation. Treatment with 10
      mg/kg per day cyclosporine prevented rejection in 70% of fetal and 75% of adult
      grafts, while all newborn grafts were rejected. Under no immunosuppression, or
      with low doses of cyclosporine (2 mg/kg per day), all groups showed histologic
      signs of rejection in almost all cases, the fetal intestine being the least
      affected. Concerning histocompatibility barriers, grafts were usually less
      damaged in the weaker transplantation subgroups. Our data indicate that fetal
      intestine is the least immunogenic of the three grafts studied, suggesting that
      it will be the most suitable tissue for organ donation.

PMID- 10955564
TI  - Waugh's syndrome: a report of six patients.
AB  - Waugh's syndrome (WS) is the association of intussusception and intestinal
      malrotation. The association has not been widely reported in the literature. In
      the only prospective study, Brereton et al. reported a high frequency of the
      association, which suggests non-random association. Six patients with this
      association presented to our unit over a 4-month period. The clinical findings
      and management are presented and discussed. We suggest that malrotation by its
      very nature is associated with a mobile right colon, which may be a prerequisite
      for intussusception.

PMID- 10955565
TI  - The relation between human leukocyte antigen (HLA) distribution and intestinal
      obstruction and adhesions in childhood: preliminary report.
AB  - To investigate the association between the human leukocyte antigen (HLA) system
      and adhesions causing intestinal obstruction in childhood in order to determine
      whether HLA profiles can be used to identify and screen individuals at risk for
      intestinal adhesions, clinical and laboratory evaluations were done in a total of
      42 (F:M = 27:15) patients. The mean age was 6.11 +/- 3.2 years (0.6-13 years).
      The patients were tested for HLA phenotype in two groups; the HLA phenotype
      distribution and relative risk (RR) for adhesions were determined. The study
      patients were children operated upon due to acute abdominal emergencies. Group 1
      included patients who needed readmission after the surgery due to intestinal
      obstruction (n = 19), group 2 patients had no readmission for any reason
      following surgery (n = 23). Of the 19 patients in group 1, 9 were treated only
      medically and 10 needed surgical intervention. Among the patients in whom medical
      treatment was initiated (n = 14), 5 needed surgery during follow-up. There was an
      increased RR for certain HLA subtypes (A24 [9], HLA11, DR11 [5], B22) in patients
      presenting with intestinal obstruction due to adhesions. Among these, A24 (9) and
      DR11 (5) were statistically significant (P < 0.05) compared with the control
      group. Several possible mechanisms could link the HLA system with disease,
      especially those in which the immune response is suspected to be involved, but
      the questions of how the inflammatory response is initiated and the role of
      proinflammatory cytokines remain unclear. Future research developments are likely
      to focus on increased understanding of the molecular biology of the major
      histocompatibility complex and its biological function in the immune response and
      adhesion formation and intestinal obstruction. It is possible that HLA profiles
      can be used to identify individuals at risk for intestinal adhesions in the
      future.

PMID- 10955566
TI  - Meconium peritonitis in utero.
AB  - To clarify the relationship between clinical features in utero and postnatal
      prognosis, 20 fetuses who underwent ultrasonic (US) evaluation for meconium
      peritonitis (MP) over a 17-year period were reviewed. According to final US
      findings in utero, patients were classified into three types. Type I (massive
      meconium ascites) was noted is 5 cases, type II (giant pseudocyst) in 4, and the
      other 11 were classified as type III (calcification and/or small pseudocyst).
      Abdominal calcifications were identified in only 5 cases (2 type I, 1 type II, 2
      type III). Seven fetuses who had associated polyhydramnios (1 Type I, 1 Type II,
      2 Type III) and fetal hydrops (3 Type II) were delivered before 36 weeks'
      gestation. Cardiopulmonary resuscitation at birth was required in 9 cases (5 type
      I, 4 type II) who underwent abdominal drainage before delivery and/or immediately
      after birth. Although dilatation of the intestine was identified in 10 fetuses (2
      type II, 8 Type III), 18 had intestinal atresia and 2 had fecal obstruction of
      the distal ileum. Four infants (2 type I, 1 type II, 1 type III) died of
      respiratory failure and postoperative complications. These results indicated that
      careful fetal US may be useful for perinatal management of MP.

PMID- 10955568
TI  - Ovarian torsion in inguinal hernias.
AB  - The possibility of sustaining ovarian damage as a consequence of an inguinal
      hernia becoming strangulated is well recognised. However, the mechanism by which
      this gonadal damage occurs is rarely stated; it is assumed that the injury is
      secondary to compression of ovarian vessels by an entrapped bowel loop. Eleven
      cases of ovarian torsion within an inguinal hernial sac are reported. In all
      cases the primary aetiological event was torsion of the ovary and tube on its
      pedicle whilst suspended from the neck of the hernial sac. This mechanism
      constituted the major cause of ovarian damage within irreducible herniae in our
      series.

PMID- 10955567
TI  - Hydrostatic reduction of intussusception: barium, air, or saline?
AB  - While there is agreement that hydrostatic reduction (HR) is the ideal first-line
      treatment for childhood intussusception, there is controversy about which
      technique is best, namely, barium, air, or saline. We present our experience in
      the Pediatric Surgical Center, University of Alexandria, in HR of intussusception
      under ultrasound (US) guidance. The study was divided into two phases: between
      1983 and 1990 and between 1991 and 1998. HR was started gradually in phase I, and
      became routine in phase II. Diagnosis and reduction were done by the pediatric
      surgical staff. The success rate was 71.7% in phase I and 85.5% in phase II. Most
      unreduced cases were the ileo-ileocolic type: 58.6% in phase I and 69.3% in phase
      II. HR under US guidance is equal or superior to other techniques of reduction,
      while having the obvious advantage of avoiding radiation exposure.

PMID- 10955569
TI  - Congenital urethrocutaneous fistula.
AB  - Congenital urethral fistula is an extremely rare but easily manageable anomaly
      that may be confused with hypospadias. This is a case description of a congenital
      fistula of the anterior urethra. Awareness of the entity will avoid
      complications.

PMID- 10955570
TI  - Anorectal injuries in children.
AB  - Anorectal injuries (ARI) are uncommon in children in civil practice. In developed
      countries the injuries are mainly due to sexual abuse and firearms. This report
      reviews the experience in tropical Africa. A retrospective study of children aged
      12 years or less managed for ARI over 10 years was undertaken. There were seven
      children, four girls and three boys. Four injuries were due to blunt trauma and
      three to penetrating trauma. Six patients presented within 6 h of injury and one
      after 24 h. Five had rectal bleeding, which was associated with vaginal bleeding
      in one girl. One girl each had vaginal bleeding and vaginal discharge without
      rectal bleeding. Diagnosis was by rectal examination and proctoscopy. In three
      patients a laparotomy was necessary to exclude an intraperitoneal rectal injury
      (IRI); this was positive in one case. One patient with abdominal findings had a
      laparotomy as the primary procedure. Overall, five patients had rectal injuries
      (extraperitoneal 3, intraperitoneal 2), which were associated with an anal injury
      in three while one patient had only an anal injury. An IRI was missed at initial
      assessment in one girl. Associated injuries were to the vaginal wall (3), urethra
      (1) and head (1). IRIs were treated by repair and proximal colostomy.
      Extraperitoneal injuries were treated by colostomy and drainage; in two patients
      the injuries were accessible and were repaired. Anal and external-sphincter
      injuries were repaired in two cases. Vaginal lacerations were repaired and other
      associated injuries treated accordingly. Three patients had wound infections.
      Faecal continence was maintained in all patients who had anal and external
      sphincter injuries. One girl died of peritonitis from a missed IRI. It is
      concluded that ARI remains uncommon in children. Morbidity and mortality can,
      however, be high. Meticulous rectal palpation and visualisation is necessary to
      avoid missing injuries.

PMID- 10955571
TI  - Window rectostomy: an alternative method of fecal diversion for high anorectal
      malformations in males without a urinary fistula.
AB  - This report analyzes our initial experience with window rectostomy (WR) as a new
      method of fecal diversion for high anorectal malformations (ARM) in 27 males
      without a urinary fistula between May 1994 and May 1998; total correction was
      achieved in two stages. In the first stage, during the neonatal period, the
      dilated rectum was exteriorized as a WR through the left lower abdomen. In the
      second, after 3-5 months an abdominoperineal pull-through (APPT) procedure was
      performed in which the window rectostomy was mobilized and taken down to form a
      new anus. The results were compared with cases of high ARM with urinary fistula
      that were managed in three stages, i.e., proximal sigmoid colostomy, APPT, and
      colostomy closure. All 27 cases showed satisfactory results without any mortality
      or major pelvic infection. The main advantages of WR are that it provides more
      functioning bowel length after diversion and avoids a colostomy-closure operation
      and repeated hospitalizations, thus reducing the total cost of treatment.

PMID- 10955572
TI  - Penoscrotal inversion, hypospadias, imperforate anus, facial anomalies, and
      developmental delay: definition of a new clinical syndrome.
AB  - We describe a 2-month-old boy with penoscrotal inversion, hypospadias,
      imperforate anus, facial anomalies, developmental retardation, and a subtelomeric
      deletion of chromosome 13q. His phenotype with anogenital malformations and
      characteristic facies closely resembled two unrelated patients with minute
      deletions of chromosome 13q who we reported earlier. In addition, he had
      unilateral renal agenesis. We propose that these patients represent a clinically
      recognizable, novel chromosomal microdeletion syndrome. The findings indicate the
      presence of a major gene(s) on chromosome 13q33.2qter that regulate(s) the
      migration and development of ano-reno-genital cells and organs. We speculate that
      mutations of this developmental gene(s) may also result in more frequent
      congenital malformations (isolated hypospadias, uterus bicornis, unilateral renal
      agenesis). Additional studies are needed to further delineate the genetic defect.

PMID- 10955573
TI  - Cortisol and adrenocorticotropic hormone response to surgical stress
      (splenectomy) in thalassemic patients.
AB  - Many vital organs, including the endocrine glands, are affected by iron
      deposition in thalassemic (Thal.) patients. Involvement of the adrenal gland,
      although not uncommon, is usually not clinically evident, especially in non
      stressful situations. Although the pituitary-adrenal axis (PAA) has been
      evaluated by several investigators, the impact of surgical stress has not yet
      been assessed. Do Thal. patients have an adequate adrenocorticotropic hormone
      (ACTH) cortisol response upon surgical insult? The PAA of 27 (8 female, 19 male)
      Thal. patients aged 4-15 years (mean 8.96) admitted during 1996-1997 for
      splenectomy was evaluated before and after surgical stress. Blood samples for
      measurement of ACTH and cortisol were taken 1 day before and about 2 h after the
      surgical insult. For comparison, 22 (9 female, 13 male) non-thalassemic (N.
      Thal.) patients aged 3.5-14 years (mean 7.95) admitted for elective laparotomy
      who had no evidence of chronic disease or malnutrition served as controls. Timing
      of blood sampling was similar to that of the study group. The cortisol response
      after surgical stress was significantly higher than baseline for both the Thal.
      (17.4 +/- 6.3 vs 30.81 +/- 11.49 microg/dl; P < 0.001) and N. Thal. groups (20.65
      +/- 9.1 vs 36.87 +/- 11.08 microg/dl; P < 0.001). N. Thal. patients showed
      significant elevation of ACTH upon surgical stress (72.5 +/- 39.5 vs 129.09 +/-
      67.9 pg/ml; P < 0.001), while the difference between pre- and post-stress was not
      statistically remarkable in Thal. patients (104.15 +/- 60.74 vs 186.8 +/- 246.24
      pg/ml; P = 0.123). However, ACTH before operation in Thal. was significantly
      higher than that of N. Thal. patients (104.15 +/- 60.74 vs 72.5 +/- 39.5 pg/ml; P
      < 0.042), with no remarkable difference after surgical stress between both groups
      (186.8 +/- 246.24 vs 129.09 +/- 67.9; P = 0.261). The serum ferritin in 8 of 13
      young Thal. patients (4-8 years old) was < 2,000 ng/ml and 2,000-3,000 in the
      remaining 5, while in the 14 older patients (9-15 years) it was < 2,000 in 5,
      2,000-3,000 in 7, and more than 3,000 ng/ml in the oldest 2 (13 and 15 years).
      The PAA is usually intact and responsive in Thal. patients. However, the
      underlying cause of the significantly increased preoperative ACTH concentrations
      may be a decreased adrenal reserve, presumably related to age and iron load. For
      this reason, the possibility of primary partial or early adrenal insufficiency in
      spite of adequate but probably less than expected cortisol synthesis before and
      after surgical stress should be considered in every prepubertal or older Thal.
      patient.

PMID- 10955575
TI  - Primary pyogenic psoas abscess in children.
AB  - Primary pyogenic psoas abscess, although quite a common condition, particularly
      in the tropics, is often overlooked as a clinical entity, probably because a
      psoas abscess has been traditionally associated with tuberculous spondylitis. The
      abscess is easily diagnosed by ultrasonography (US). Treatment by open drainage
      and antibiotics effective against Staphylococcus aureus results in complete
      reversal of symptoms and signs. In our series of 55 cases in the pediatric age
      group (0-12 years), pain and flexion at the hip were the most frequent clinical
      features at presentation. US was diagnostic in all cases in which it was
      performed. All except 1 patient showed complete resolution with extraperitoneal
      drainage, antibiotics, and skin traction. Although 4% of the cases were
      associated with suppurative external-iliac lymphadenitis, the remaining ones
      arose de novo in the psoas sheath, suggesting a primary pyomyositis of the psoas
      muscle.

PMID- 10955574
TI  - Morbidity in infants with antenatally-diagnosed anterior abdominal wall defects.
AB  - The aims of this study were to compare the morbidity of infants with
      gastroschisis (GS) with that of infants with exomphalos (EX) without lethal
      abnormalities and to identify factors predictive of adverse outcome: a
      requirement for parenteral nutrition (PN) for over 1 month and hospital admission
      for over 2 months. The medical records of 45 infants with anterior wall defects
      (32 with GS) diagnosed antenatally who consecutively received intensive care in
      one institution from 1993 were reviewed. Both the GS and EX infants had a median
      gestational age of 37 weeks, but the former were lighter at birth (P < 0.01).
      Fourteen infants (all with GS) were able to start feeds only after 2 weeks; 10 (8
      with GS) developed liver dysfunction; and 5 (all with GS) died. The GS compared
      to the EX infants required a longer period of PN (median 20 vs 10 days, P < 0.01)
      and longer hospital admission (median 40 vs 25 days, P < 0.01). In the GS group
      the time to start feeding related independently to prolonged hospital stay, and
      the existence of structural bowel abnormalities (SBA) related independently to
      both measures of adverse outcome, with a positive predictive value of 100%. We
      conclude that infants with GS, particularly those with SBA, suffer greater
      morbidity than infants with EX without lethal abnormalities.

PMID- 10955576
TI  - Venous patency after open central-venous cannulation.
AB  - To investigate the value of Doppler ultrasound scan (USS) assessment of internal
      jugular vein (IJV) patency after previous open central-venous cannulation (CVC),
      a prospective study of 66 consecutive children (median age 4.5 years; range 4
      months-17 years) who had previously undergone open insertion of at least one
      indwelling IJV line and required further CVC for completion of therapy was
      undertaken. All underwent Doppler USS examination prior to surgery. Where patency
      of the previously cannulated vein was suggested ultrasonographically, the
      accuracy of this finding was confined at open surgical exploration. Initial CVCs
      were in situ for a median of 9 months (1 month-4 years) prior to removal. The
      median interval to repeated CVC was 11 months (3 weeks-45 months). In 79 Doppler
      USS, 70 (88.6%) veins appeared patent, 3 (4.2%) stenosed, and 6 (7.6%)
      obliterated. Of the 70 "USS patent" veins, 66 were explored. Patency was
      confirmed surgically in 59 (89.4%) and a new CVC successfully inserted. Seven
      (10.6%) apparently patent veins on USS were found to be obliterated at open
      exploration. Review of USS images in these cases suggested that enlarged
      collateral veins were usually responsible. Overall, successful recannulation was
      possible in 74.6% of all previously accessed veins. In children requiring
      repeated CVC, Doppler USS of neck veins is a valuable but not entirely reliable
      guide to the presence of underlying vessel patency and should be interpreted with
      caution. At least three-fourths of previously cannulated IJVs remain patent after
      catheter removal and can be reused for CVC.

PMID- 10955577
TI  - Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis
      in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia
      in rats.
AB  - The aim of this study was to investigate the effect of antenatal glucocorticoid
      therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA)
      in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following
      nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX)
      was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine
      (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were
      killed by cesarean section at term. The fetuses were divided into three groups:
      group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group
      III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining
      of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin
      complex method. The number of immunopositive cells in the PA media and adventitia
      were counted using an image analyzer and analyzed statistically. The number of
      BrdU-immunopositive cells in the media was significantly increased in group II
      (16.83 +/- 3.01) compared to groups I (9.16 +/- 2.20) and III (6.83 +/- 1.70) (P
      < 0.01). There was no significant difference between groups I and III. The number
      of BrdU-immunopositive cells in the adventitia was not significantly different
      between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in
      PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX
      prevents structural PA changes in nitrofen-induced CDH in rats.

PMID- 10955578
TI  - Incidence of surgical site infections in pediatric patients: a 3-month
      prospective study in an academic pediatric surgical unit.
AB  - During a 3-month period 259 pediatric surgical procedures in 236 patients were
      followed for the development of surgical site infections (SSI): 17 sites became
      infected, an overall infection rate of 6.6%. The incidence in our study was
      therefore higher than expected. As expected, the infection rate increased
      according to wound contamination: dirty sites had a SSI rate of 30%. Emergency
      procedures, operation duration over 1 h, and inpatients showed a statistically
      significant higher risk of developing SSI. Although there were differences
      between males and females, individual surgeons, and the use of antibiotic
      prophylaxis, these differences were not statistically significant.

PMID- 10955579
TI  - Rotary atlanto-axial subluxation with torticollis following central-venous
      catheter insertion.
AB  - Atlanto-axial subluxation with torticollis is an uncommon condition that occurs
      in children usually as a result of pharyngeal infection, minor trauma, or neck
      surgery. Passive motion of the head and neck during general anesthesia is
      probably another etiologic factor. Torticollis is the most common presenting
      physical finding. Pain may or may not be present, but is commonly present with
      passive neck motion. Neurologic sequelae are uncommon. Our case illustrates this
      condition as a complication of central venous catheter (CVC) insertion in a child
      under general anesthesia. The surgeon should suspect this pathology when a child
      presents with torticollis following CVC placement. Precautions should be taken in
      the operating room to avoid aggressive rotation and extension of the child's neck
      while under general anesthesia whether or not cervical inflammation is present.
      Special attention to head and neck positioning should be taken in patients with
      Down's syndrome since they are at increased risk for atlanto-axial subluxation.
      The prognosis is excellent when diagnosed early. A delay in diagnosis can result
      in the need for surgical intervention.

PMID- 10955580
TI  - Antral web--a rare cause of vomiting in children.
AB  - Antral web is a rare cause of gastric-outlet obstruction. We report a case of
      gastric antral web with intermittent vomiting in a 10-year-old girl who received
      medical treatment for 6 months. The literature on this anomaly is reviewed with
      respect to differential diagnosis on the basis of upper gastrointestinal
      radiographic series, gastroscopy, and treatment planning.

PMID- 10955581
TI  - Nesidioblastosis with necrotising enterocolitis: an enigma.
AB  - Necrotising enterocolitis with nesidioblastosis is a rare, lethal coexistence
      during the newborn period. We report this unusual combination leading to surgery:
      a partial pancreatectomy and resection with primary anastomosis, and discuss the
      dilemma of the procedure of choice during therapy.

PMID- 10955582
TI  - Gastric wall erosion by an amebic liver abscess in a 3-year-old girl.
AB  - The occurrence of an amebic liver abscess (ALA) rupturing into the stomach is
      reported. ALAs in children can have atypical presentations, resulting in delayed
      diagnosis and increased morbidity and mortality. Timely treatment is usually
      followed by complete recovery.

PMID- 10955583
TI  - Caroli syndrome.
AB  - We describe a case of Caroli syndrome (Caroli's disease and congenital hepatic
      fibrosis) in a 10-year-old boy with bilobar involvement and numerous renal cysts.
      Liver transplantation offers the only hope for such patients.

PMID- 10955584
TI  - Congenital spigelian hernia and cryptorchidism: cause or coincidence?
AB  - Congenital spigelian hernia (SH) is very rare in the pediatric age group. This is
      a report of two cases of SH in 1-week and 3-month-old male infants. A review of
      the literature revealed only 35 cases of SH in children younger than 17 years of
      age, bringing the total including our 2 cases to 37. There were 25 males and 12
      females, a ratio of 2.1:1. Their ages ranged from 6 days to 17 years (mean 4.52
      years). The hernia was situated on the right side in 13, the left side in 19, and
      was bilateral in 4. In one case the side of the hernia was not mentioned. In 29
      cases the hernia was spontaneous while in 5 it was caused by trauma. In 3
      children the hernia developed postoperatively, in 2 following repair of a
      congenital diaphragmatic hernia and in 1 following excision of a mediastinal
      neuroblastoma. Two children presented with a strangulated SH. Eleven of the 35
      previously reported children had associated conditions; in 5 there was an
      ipsilateral undescended testis (UDT). Our two infants with SH also had an
      ipsilateral UDT. The significance of this association is discussed.

PMID- 10955585
TI  - Peutz-Jeghers syndrome: is family screening needed?
AB  - In a 7-year-old boy, a small-bowel polyp was found intraoperatively as a lead
      point of an intussusception. Histologically, a hamartoma was found and the
      clinical work-up revealed Peutz-Jeghers syndrome (PJS). Additionally, all four
      asymptomatic siblings showed intestinal polyposis. All children in a family with
      PJS should be properly investigated. In case of an intussusception with a polyp
      in a critical location, a surgical procedure should follow.

PMID- 10955586
TI  - Indications for laparotomy in infection with verotoxigenic Escherichia coli.
AB  - Verotoxigenic types of Escherichia coli have emerged as serious and important
      human pathogens. The clinical disease most frequently manifests as a painful form
      of bloody diarrhea, which can progress to life-threatening systemic
      microangiopathic hemolytic anemia, known as the hemolytic-uremic syndrome (HUS).
      Three children with hemorrhagic enteritis due to verotoxigenic E. coli are
      presented to illustrate the unique diagnostic, therapeutic, and operative
      management dilemmas associated with this disease. When contemplating surgery, one
      should seek to determine the anatomic and transmural extent of the disease.

PMID- 10955587
TI  - Spontaneous scrotal faecal fistula in an infant.
AB  - A 2-month-old, full-term male presented with a left scrotal faecal fistula due to
      spontaneous bursting of an incarcerated inguinal hernia for 8 days, with complete
      decompression of the small bowel through it. Resection and end-to-end anastomosis
      of the engaged ileal loop was successfully done after incising the ring via the
      inguinal approach. Only two such cases have been reported in the world literature
      to date.

PMID- 10955588
TI  - Caudal duplication--a case report.
AB  - Caudal duplication is a rare entity due to incomplete separation of mono-ovular
      twins. It is usually associated with various congenital malformations involving
      mainly the genitourinary and gastrointestinal tracts. We report such a case
      operated upon successfully in which there was no other associated anomaly.

PMID- 10955589
TI  - Wilms' tumor with vena caval, atrial, and middle hepatic vein tumor thrombus.
AB  - A 3-year-old male with a right-sided Wilms' tumor presented with tender
      hepatomegaly and bilateral lower-limb edema. Ultrasound and echocardiography
      showed a massive tumor thrombus completely occluding the inferior vena cava,
      right atrial cavity, and extending retrogradely into the middle hepatic vein. Two
      courses of preoperative chemotherapy (vincristine, actinomycin D, adriamycin)
      caused minimal shrinkage of the thrombus. The tumor and thrombus were
      successfully removed with the patient under cardiopulmonary bypass and deep
      hypothermic circulatory arrest followed by multiagent chemotherapy (vincristine,
      actinomycin D, adriamycin, cyclophosphamide). The child is alive and well with no
      evidence of disease 15 months later. Occlusion of the hepatic vein by a tumor
      thrombus in Wilms' tumor is a very rare event. It was completely removed by the
      right atrial route under direct vision in this child.

PMID- 10955590
TI  - Rhabdoid tumour of the kidney: a diagnostic challenge and a fatal outcome.
AB  - Rhabdoid tumour of the kidney is not common. Presentation of such a lethal tumour
      along with blunt abdominal trauma is even rarer. We report such a case of
      Rhabdoid tumour of kidney which presented as renal trauma, and discuss the
      diagnostic difficulties and rapidly fatal outcome.

PMID- 10955591
TI  - Pitfalls in the interpretation of MIBG scans in cervical neuroblastoma.
AB  - Cervical neuroblastoma (CNB) is relatively rare, accounting for less than 5% of
      these tumors. Because it arises from the cervical sympathetic chain, complete
      resection will leave the child with Horner's syndrome in a high proportion of
      cases. Advances in technology have allowed for the development of diagnostic and
      imaging modalities more specific to the disease. One of these has been the advent
      of radiolabeled meta-iodobenzylguanidine (MIBG) to assess the primary tumor and
      focal metastatic involvement. This nuclide is also taken up by normal salivary
      gland tissue; this may be altered, however, in the presence of sympathetic
      denervation. We present a case of a primary CNB associated with Horner's
      syndrome, which led to confusion in interpretation of the subsequent MIBG scan.
      We alert the reader to potential pitfalls in the use of this examination in this
      disease entity.

PMID- 10955592
TI  - Posttraumatic high-flow priapism: treatment with selective embolisation.
AB  - Priapism is an uncommon problem in childhood. Most of the reported cases are in
      boys with sickle-cell disease or leukaemia. It occurs as a result of venous
      outflow obstruction, resulting in engorgement of the corpora cavernosa, and is
      termed "low-flow" priapism. In a small group of children priapism is due to
      uncontrolled arterial inflow, usually as a result of direct trauma. The authors
      report a case of posttraumatic arterial priapism in a child, successfully treated
      with selective embolisation of the internal pudendal artery. Recognition of this
      distinct entity is important, as it carries a good prognosis when appropriately
      treated.

PMID- 10955593
TI  - Multiple neurilemmomas of the penis.
AB  - A 10-year-old male with multiple small swellings over the shaft of the penis for
      2 years was found to have multiple neurilemmomas on histopathologic examination.
      The case is reported in view of the extreme rarity of the entity.

PMID- 10955594
TI  - Lipoblastoma: better termed infantile lipoma?
AB  - Lipoblastoma is a rare adipose tumor occurring exclusively in childhood. There
      have been no reports of metastases, making the designation "blastoma" confusing,
      since this term is usually reserved for malignant tumors. Two recent cases
      treated at our institution confirm its benign nature. In addition, a review of
      the literature supports the idea that the tumor may more accurately be described
      as an "infantile lipoma". Infantile lipoma better reflects many of the tumor's
      characteristics such as, its early occurrence, it's ability to mature into a
      simple lipoma, it's cellular composition of mainly mature adipocytes, and its
      benign course. Although lipoblastoma is an uncommonly encountered tumor, making
      an effort to change its name to infantile lipoma will result in a more a accurate
      term that will facilitate treatment.

PMID- 10955595
TI  - Functions of peripheral 5-hydroxytryptamine receptors, especially 5
      hydroxytryptamine4 receptor, in gastrointestinal motility.
AB  - The multiple 5-hydroxytryptamine (5-HT, serotonin) receptor subtypes are
      distinguished. In this article, we described mainly the 5-HT4 receptor of four
      subtypes of functional 5-HT receptors, 5-HT1, 5-HT2, 5-HT3, and 5-HT4, recognized
      in the gastrointestinal tract. In-vivo microdialysis experiments determined that
      activation of the 5-HT4 receptor stimulated intestinal motor activity associated
      with a local increase in acetylcholine (ACh) release from the intestinal
      cholinergic neurons in the whole body of dogs. The 5-HT4 receptor-mediated
      response of ACh release in the antral, corporal, and fundic strips isolated from
      guinea pig stomach corresponds to the presence of 5-HT4 receptor in the myenteric
      plexus. In-vitro receptor autoradiograms of the stomach and colon indicate that
      the distribution of 5-HT4 receptors in human tissues is similar to that in the
      guinea pig, although density of 5-HT4 receptors in the myenteric plexus of human
      tissues is lower than that in guinea pig tissues. The 5-HT4 receptors located in
      the myenteric plexus may participate in gastrointestinal motility, and thus the 5
      HT4 agonists and antagonists may be available for treatment of dysfunction of
      gastrointestinal motility.

PMID- 10955596
TI  - Prevalence of Barrett's esophagus and expression of mucin antigens detected by a
      panel of monoclonal antibodies in Barrett's esophagus and esophageal
      adenocarcinoma in Japan.
AB  - Barrett's esophagus (BE) is an acquired disorder associated with a high incidence
      of adenocarcinoma of the lower esophagus. Moreover, it has been reported that
      short-segment BE may be associated with adenocarcinoma of the esophagogastric
      junction. The objective of this study was to define the prevalence of BE and the
      mucin profile in BE, including the short-segment type, and to compare the mucin
      profile in BE with the profiles of Barrett's adenocarcinoma and distal esophageal
      adenocarcinoma among Japanese. In total, 650 adult subjects underwent endoscopic
      examination for evaluation of BE. Although the prevalence of traditional (long
      segment) BE was 0.62%, the overall prevalence of BE including short-segment type
      was 15.7%. In Barrett's epithelium, the short-segment type predominantly had
      gastric type mucin, while the middle- and long-segment types possessed intestinal
      mucin, especially colonic type mucin (sulfo-Lewis(a)), with high frequency. In
      Barrett's epithelium with adenocarcinoma, all Barrett's epithelium adjacent to
      carcinomas showed a predominance of immunoreactivity to sulfo-Lewis(a). In
      Barrett's adenocarcinomas, colonic type mucin was detected in 100% by monoclonal
      antibody (MoAb) 91.9H. Small-intestinal mucin and gastric mucin were stained in
      50% and 12.5% of the subjects, respectively. Colonic type mucin was also detected
      with high frequency (80%) in distal esophageal adenocarcinomas without Barrett's
      epithelium. These data suggest that the epitope, not of small-intestinal type or
      gastric type mucin, but of colonic type mucin (sulfo-Lewis(a)), may be associated
      with, at least in part, the malignant phenotype of BE.

PMID- 10955597
TI  - Cold pain prolongs gastric emptying of liquid but not solid meal: an electrical
      impedance tomography (EIT) study.
AB  - Stressful stimuli are reported to affect gastric emptying. However, methods for
      measuring gastric emptying are, in themselves, stressful. Electrical impedance
      tomography (EIT) is a method for measuring gastric emptying noninvasively. We
      used EIT to measure gastric emptying of liquid and solid meals to determine the
      effect of cold pain stress on gastric emptying. EIT (DAS-01P APT system;
      University of Sheffield, UK) was carried out in six healthy women (age, 21.6 +/-
      0.4 [mean +/- SD] years) who had ingested a liquid (potage, 263 g; 139 kcal) or
      solid (beef patty, 205 g; 435 kcal) test meal. Cold pain stimuli consisted of
      repeated immersions of the subject's non-dominant hand into ice water (4 degrees
      C) for 1 min, with a 15-s recovery period between immersions, for a total of 20
      min. For the control stimulus, water at 37 degrees C was used. The cold pain
      stimulus was applied immediately after the ingestion of a test meal. All studies
      were carried out randomly in each subject at intervals of more than 1 week. With
      cold pain, the half emptying time of the liquid meal was significantly greater
      than that with the control stimulus (47.6 +/- 26.1 min vs 28.1 +/- 10.8 min, P <
      0.05). For the solid meal, the half emptying time did not differ between stimuli
      (101.9 +/- 44.8 min with cold pain vs 92.6 +/- 30.5 min with control stimulus).
      There were no significant differences in lag time between the liquid and solid
      meals. Cold pain stress delayed gastric emptying of liquid but not solid meals.

PMID- 10955598
TI  - Epidermal growth factor receptor-binding growth factors in the urine of patients
      with cancers of the digestive tract.
AB  - We aimed to assess the diagnostic application of urinary epidermal growth factor
      receptor (EGFR)-binding growth factors in cancers of the digestive tract. By
      radioreceptor assay and radioimmunoassay, we determined these growth factors in
      115 patients with various cancers of the digestive tract, 30 patients with benign
      disease, and 40 healthy controls. The receiver operating characteristic (ROC)
      curve and likelihood ratio were employed to determine the best diagnostic
      efficiency. Urinary EGFR-binding growth factors in each cancer group were
      significantly higher than those in the non-cancer groups. Multivariate analysis
      indicated that the growth factors, determined by both the radioreceptor assay
      (odds ratio, 1.184; 95% confidence interval,1.077-1.302; P = 0.001) and
      radioimmunoassay (odds ratio,1.055; 95% confidence interval, 1.002-1.111; P =
      0.039), were associated, in a dose-related fashion, with the presence of cancers.
      By ROC curve analysis, the optimal cutoff values for EGFR-binding growth factors
      were 25.5 microg/g creatinine (radioreceptor assay) and 33.6 microg/g creatinine
      (radioimmunoassay). The resulting sensitivity, specificity, diagnostic accuracy,
      and positive and negative likelihood ratios were 84.4%. 87.5%, 85.2%, 6.75 and
      0.18 (for radioreceptor assay) and 86.1%, 67.5%, 81.3%, 2.64 and 0.21 (for
      radioimmunoassay), respectively. Except for pancreatic cancer the growth factors
      showed moderate diagnostic efficiency for the other digestive tract cancers. In
      conclusion, urinary EGFR-binding growth factors were increased in cancers of the
      digestive tract. They may be used as diagnostic tumor markers.

PMID- 10955599
TI  - Increased response rate to interferon therapy after a second course in hepatitis
      C patients who show relapse after the initial course.
AB  - Some patients with chronic hepatitis C become HCV-RNA seronegative during
      interferon (IFN) therapy. However, about one-half of these patients show a
      relapse, evident by high serum alanine aminotransferase (ALT) level. In some
      patients with biochemical relapse, the serum HCV-RNA level becomes low
      immediately after the ALT relapse. Here, we assessed the changes in serum HCV-RNA
      level in patients with ALT relapse after IFN therapy, and evaluated the efficacy
      of a second course of IFN, started at the recovery stage after ALT relapse. Two
      hundred and seventy-seven patients who showed HCV-RNA seronegativity by reverse
      transcription nested-polymerase chain reaction (RT nested-PCR) and normalization
      of ALT during the initial IFN therapy, and had positive HCV-RNA with ALT relapse
      (> 100 IU/l) within 3 months after completion of the initial IFN course were
      enrolled in this retrospective study. Two hundred and sixty patients were
      followed-up without further IFN retreatment after the ALT relapse (group 1), and
      17 patients received another 6-month course of IFN after the ALT relapse (group
      2). The median level of serum HCV-RNA, determined with a branched DNA probe assay
      (version 1; Chiron-Dai-ichi Kagaku Tokyo, Japan), in group 1 was 3.1 Meq/ml
      before IFN therapy, 1.3 Meq/ml at the time point of the ALT peak after the
      completion of IFN therapy, and 0.7 and 2.6 Meq/ml at 2-4 and 6-8 weeks after the
      ALT peak, respectively. The serum HCV-RNA level at 2-4 weeks after the ALT peak
      was lower than that before IFN therapy. The eradication rate of HCV-RNA (complete
      response; CR) in group 2 (47.1%; 8/17) was significantly higher than that in
      group 1 (1.5%; 4/260; P < 0.001). In conclusion, our data suggested that: (1)
      patients who showed biochemical relapse after initial IFN therapy had a
      significantly lower serum HCV-RNA level at recovery after ALT relapse compared
      with that before initial IFN therapy. (2) A high response rate was noted after a
      second course of IFN administered at the recovery stage of the ALT relapse,
      compared with patients without IFN retreatment.

PMID- 10955600
TI  - Evolution of and obstacles in surgical treatment for hepatocellular carcinoma
      over the last 25 years: differences over four treatment eras.
AB  - This study was designed to clarify what differences the last 25 years have made
      in surgical results for patients with hepatocellular carcinoma (HCC). We examined
      results for 716 hepatectomized patients in four treatment eras: first era (1973
      1980; n = 58), second era (1981-1985; n = 155), third era (1986-1990; n = 243),
      and fourth era (1991-1997; n = 260). Patient background, tumor characteristics,
      type of hepatectomy, treatment for intrahepatic recurrences, and surgical results
      in the four eras were compared by univariate analysis to clarify the factors that
      have contributed to or impeded progress in the surgical treatment of HCC.
      Although there were no significant chronological differences in liver pathology
      and surgical resectability, operative mortality was reduced to 2% in the fourth
      era, from 29% in the first era. With an increasing proportion of early-stage HCCs
      (TNM, stages I and II), the cumulative survival rate at 5 years improved in the
      course of the eras in our overall population of patients (12%, 31%, 38%, and 51%,
      respectively, for the first, second, third, and fourth eras) and in a subset of
      the population divided according to tumor stage. Also, we found a chronological
      improvement in the survival rate at 3 years after intrahepatic recurrence (10%,
      28%, 36%, and 44%, respectively in the first second, third, and fourth eras).
      This improvement was associated with the establishment of an early detection
      program for intrahepatic recurrences. However, the recurrence rate was similar in
      any subset of the population through the four eras. Although this univariate
      study could not determine independent factors that contributed to the
      chronological progress in results for HCC surgery in the four eras, it is
      conceivable that the establishment of indication criteria for hepatectomy, an
      early detection program for primary and recurrent lesions, and the introduction
      of multimodal treatment for recurrence were contributory factors in this
      improvement. A strategy for alleviating the frequent recurrences originating from
      posthepatectomy metachronous carcinogenesis remains to be established.

PMID- 10955601
TI  - Percutaneous recanalization of the bile duct along an endoscopic naso-biliary
      catheter.
AB  - Percutaneous recanalization of the bile duct is essential for placing biliary
      stents and carrying out other interventions. This prospective study was performed
      to establish safe approaches for percutaneous recanalization of the bile duct
      when it had previously resulted in failure. Between July 1995 and July 1999,
      percutaneous recanalization of the bile duct was attempted in 58 patients with a
      malignant biliary stenosis. When recanalization failed, an endoscopic naso
      biliary drainage (ENBD) catheter was placed across the stenosis. The procedure
      was again attempted along the ENBD catheter. In the period of the study, four
      patients underwent successful recanalization after ENBD, although attempts prior
      to ENBD had been unsuccessful. As a result, the success rate of recanalization in
      the period was 100% (58/58). When recanalization fails, the use of an ENBD
      catheter may provide access to the biliary tree, and the biliary stenosis can be
      recanalized safely.

PMID- 10955602
TI  - Protein-losing enteropathy associated with hypocomplementemia and anti-nuclear
      antibodies.
AB  - We report a case of protein-losing enteropathy associated with an autoimmune
      disorder, presumably systemic lupus erythematosus. Although typical
      manifestations of systemic lupus erythematosus were lacking, a high serum
      cholesterol level, a low serum complement level, positivity for anti-nuclear
      antibody, and positivity for anti-single-strand DNA antibody suggested an
      autoimmune mechanism as the cause of the condition. Although immunohistological
      examination of duodenal and ileal biopsy specimens failed to reveal deposits of
      immune complex or complement in the vessels, capillary hyperpermeability was
      suspected as the mechanism of the condition.

PMID- 10955603
TI  - Granular cell tumor of the rectum: a case report and review of the literature.
AB  - A 47-year-old Japanese woman with a 5-year history of alcoholism was admitted to
      the Ryukyu University Hospital for the treatment of the alcoholism. For
      evaluation of observed changes in her bowel habits, she underwent colonoscopy,
      which revealed seven small polyps spread throughout the entire large intestine.
      Six of the polyps were in the colon; one was an adenoma and five were
      hyperplastic polyps. The remaining polyp, in the rectum, was an 8-mm submucosal
      tumor. Pathological analysis of a biopsy of the lesion in the rectum indicated a
      possible diagnosis of adenocarcinoma. Endoscopic ultrasonography (EUS)
      demonstrated a submucosal hypoechoic nodule, involving the mucosa and the
      muscularis propria. Subsequently, the patient underwent a radical low anterior
      resection of rectum. The lesion was a submucosal tumor with ulceration. The tumor
      consisted of granular tumor cells which were positive for S-100 protein, neuron
      specific enolase, and periodic acid schiff (PAS) stain, but negative for desmin
      and vimentin. Granular cell tumor is rare in the gastrointestinal tract. As a
      result, such tumors can be misinterpreted to indicate a possible malignancy on
      either a biopsy or EUS.

PMID- 10955604
TI  - Tacrolimus in corticosteroid-resistant ulcerative colitis.
AB  - We report a case of refractory ulcerative colitis treated with tacrolimus. The
      patient was a 73-year-old woman with a 45-year history of ulcerative colitis. An
      attack unresponsive to intravenous corticosteroid therapy occurred when she was
      age 73. Leukocytapheresis therapy was attempted, but was discontinued because of
      the patient's poor general condition. Cyclosporine A therapy brought about fair
      control of the disease. A liver injury that was suspected to be associated with
      this agent, however, occurred within 5 weeks of its initiation. At that time, the
      cyclosporine A was discontinued and azathioprine treatment was started. Within 6
      weeks, signs of exacerbation of the ulcerative colitis became apparent.
      Tacrolimus administered at that time brought about remission of the disease, and
      the corticosteroid dose was then reduced. Tacrolimus, like cyclosporine A,
      appears to be effective for the treatment of attacks of ulcerative colitis.

PMID- 10955605
TI  - Inflammatory pseudotumor of the liver diagnosed by needle liver biopsy under
      ultrasonographic tomography guidance.
AB  - Inflammatory pseudotumor of the liver is a rare benign lesion, but exploratory
      laparotomy and a hepatectomy are often performed unnecessarily after various
      misdiagnoses, including liver abscess, hepatocellular carcinoma, metastatic liver
      tumor, and cholangiocarcinoma. We present a case of hepatic inflammatory
      pseudotumor in a 17-year-old man in whom diagnosis was confirmed by liver needle
      biopsy under ultrasonographic tomography (UST) guidance. He had complained of
      fever and right hypochondralgia 2 months after being operated for appendicitis.
      He was admitted to our hospital because of the persistence of these symptoms and
      the presence of a hepatic mass lesion detected by UST. He had hepatomegaly, with
      tenderness; leukocytosis and elevated erythrocyte sedimentation rate and C
      reactive protein level were noted. UST showed a hypoechoic mass in the liver and
      pre-contrast computerized tomography (CT) revealed a low-density area with an ill
      defined margin, which was barely enhanced by the contrast medium. On the basis of
      the patient's clinical symptoms and the laboratory data and imaging studies, the
      presence of a liver abscess was suspected and antibiotics were administered. One
      month after the initiation of the antibiotic therapy, UST demonstrated that the
      portal vein had dilated serpiginously and penetrated into the mass. As the
      heterogeneous appearance displayed by post-enhanced CT indicated the need for a
      differential diagnosis of the hepatic mass lesion to rule out hepatocellular
      carcinoma, percutaneous needle biopsy was performed, under UST guidance.
      Histopathological examination demonstrated marked infiltration of plasma cells
      and fibrosis, findings which were consistent with those of hepatic inflammatory
      pseudotumor. There was a spontaneous reduction of the hepatic pseudotumor without
      continuous antibiotics and this reduction was documented on follow-up UST and CT.

PMID- 10955606
TI  - Primary biliary cirrhosis associated with idiopathic retroperitoneal fibrosis.
AB  - Idiopathic retroperitoneal fibrosis (IRF) and primary biliary cirrhosis (PBC) are
      distinct clinical disorders which rarely occur in the same patient. We report a
      79-year-old man with the coexistence of both conditions. The patient had
      antibodies to both centromere and mitochondria, as indicated by indirect
      immunofluorescence. Diagnoses of IRF and PBC were confirmed histologically.
      Although the association between IRF and PBC is obscure, IRF may be involved in
      many autoimmune diseases associated with PBC.

PMID- 10955607
TI  - How should gastric emptying be evaluated and interpreted?

PMID- 10955608
TI  - A new era of interferon treatment for chronic hepatitis C is coming.

PMID- 10955609
TI  - Tacrolimus (FK506), a novel immunosuppressive drug for inflammatory bowel
      disease?

PMID- 10955610
TI  - Decibels, SI units, and standards.

PMID- 10955611
TI  - Acoustical wave propagator
AB  - In this paper, an explicit acoustical wave propagator (AWP) is introduced to
      describe the time-domain evolution of acoustical waves. To implement its
      operation on an initial state of wave motion, the acoustical wave propagator is
      approximated as a Chebyshev polynomial expansion, which converges to machine
      accuracy. The spatial gradient in each polynomial term is evaluated by a Fourier
      transformation scheme. Analysis and numerical examples demonstrated that this
      Chebyshev-Fourier scheme is highly accurate and computational effective in
      predicting time-domain acoustical wave propagation and scattering.

PMID- 10955612
TI  - Approximations for modal coupling in scattered fields from orifices
AB  - Previous investigations have used Hankel transforms to establish the velocity
      potentials of the wave fields resulting from arbitrary angle plane wave
      impingement on a circular orifice in a rigid, thick wall. The scattered field
      from the orifice is examined, in particular the modal contributions to the
      amplitude of its velocity potential. For each m,n mode the amplitude is dependent
      upon the amplitude of the in-orifice waves and a driving term unique to each m,n
      mode. In establishing the amplitudes of the in-orifice waves, the effects of
      modal coupling are also considered. In this work these two components of the
      scattered wave amplitude are investigated on a modal basis and approximations
      given for coupling effects. These approximations are then used to calculate the
      scattered field and the results compared with conventional solutions that use
      full modal coupling.

PMID- 10955613
TI  - Sound propagation over layered poro-elastic ground using a finite-difference
      model
AB  - This article presents an axisymmetric pressure-velocity finite-difference
      formulation (PV-FD) based on Biot's poro-elastic theory for modeling sound
      propagation in a homogeneous atmosphere over layered poro-elastic ground. The
      formulation is coded in a computer program and a simulation of actual
      measurements from airblast tests is carried out. The article presents typical
      results of simulation comprising synthetic time histories of overpressure in the
      atmosphere and ground vibration as well as snapshots of the response of the
      atmosphere-ground system at selected times. Comparisons with the measurements
      during airblast tests performed in Haslemoen, Norway, as well as the simulations
      by a frequency-wave number FFP formulation are presented to confirm the soundness
      of the proposed model. In particular, the generation of Mach surfaces in the
      ground motion, which is the result of the sound speed being greater than the
      Rayleigh wave velocity in the ground, is demonstrated with the help of snapshot
      plots.

PMID- 10955614
TI  - Transport parameters for an ultrasonic pulsed wave propagating in a multiple
      scattering medium
AB  - A set of ultrasonic experimental methods was developed to characterize a multiple
      scattering medium in terms of l(s), l*, l(a), respectively, the elastic,
      transport, and absorption mean free paths and D the diffusion constant. Actually,
      these quantities are the key parameters for a wave propagating in a disordered
      medium. Although they are widely used in optics, they are less common in
      acoustics. The underlying model is based on the expansion of the average solution
      for the heterogeneous Green's function equation. To validate this theoretical
      approach, a sample made of randomly located steel rods was used as a prototype.
      Through time-resolved measurements of the transmitted amplitude, the difference
      between the ballistic and the coherent wave is highlighted. In varying the sample
      thickness, l(s) is determined, the coherent and diffusive regime are
      distinguished, and the transition from one to the other is followed. Furthermore,
      as a limit to a description of the average intensity based on the diffusion
      approximation, the existence of a coherent backscattering effect is shown. This
      latter gives a method to estimate D and l*. These quantities being determined, it
      becomes possible to infer l(a) using average time-resolved intensity
      measurements. Finally, some applications to coarse-grain stainless steels are
      discussed.

PMID- 10955615
TI  - Approximate expressions for viscous attenuation in marine sediments: relating
      Biot's "critical" and "peak" frequencies.
AB  - Simple approximate relations are proposed for the viscous attenuation per cycle
      of the fast compressional and shear waves in the low-to-intermediate frequency
      range. Corresponding closed-form formulas are derived for frequencies at which
      maximum viscous attenuation per cycle occurs according to the Biot-Stoll theory
      of elastic wave propagation in marine sediments. In the new formulas, Biot's
      approximation [M. A. Biot, J. Acoust. Soc. Am. 34, 1254-1264 (1962)] for the
      frequency-dependent viscosity correction factor F(f) and the assumption of
      relatively low specific loss (Q(-1)<(0.2) [J. Geertsma and D. C. Smith,
      Geophysics 26(2), 169-181 (1962)] are used to provide an accurate representation
      of the fast compressional and shear wave attenuation from low frequencies through
      a transition region extending to two or three times Biot's critical frequency
      f(c). The approximate viscodynamic behavior of marine sediments for the fast
      compressional and shear waves shows similarities to that of a "homogeneous
      relaxation" process for an anelastic linear element [A. M. Freudenthal and H.
      Geiringer, Encyclopedia of Physics (Springer-Verlag. 1958), Vol. 6].

PMID- 10955616
TI  - Bessel beams of finite amplitude in absorbing fluids
AB  - Second-harmonic generation in a Bessel beam is investigated analytically, with
      emphasis on the effect of absorption. It is shown that absorption has a strong
      influence on the far-field beam profile. Numerical results are presented for
      higher harmonics and for waveform distortion in a Bessel beam that forms a shock.

PMID- 10955617
TI  - Calculations of internal-wave-induced fluctuations in ocean-acoustic propagation.
AB  - Variability in the ocean sound-speed field on time scales of a few hours and
      horizontal spatial scales of a few kilometers is often dominated by the random,
      anisotropic fluctuations caused by the internal-wave field. Results have been
      compiled from analytical approaches and from numerical simulations using the
      parabolic approximation into an efficient set of algorithms for calculating
      approximations to internal-wave effects on temporal and spatial coherences,
      coherent bandwidths, and regimes of acoustic fluctuation behavior. These
      approximate formulas account for the background, deterministic, sound-speed
      profile and the anisotropy of the internal-wave field, and they also allow for
      the incorporation of experimentally determined profiles of sound speed, buoyancy
      frequency, and sound-speed variance. The algorithms start from the geometrical
      acoustics approximation, in which the field transmitted from a source can be
      described completely in terms of rays whose characteristics are determined by the
      sound speed as a function of position. Ordinary integrals along these rays
      provide approximations to acoustic-fluctuation quantities due to the statistical
      effects of internal waves, including diffraction. The results from the algorithms
      are compared with numerical simulations and with experimental results for long
      range propagation in the deep ocean.

PMID- 10955618
TI  - Acoustic scattering by benthic and planktonic shelled animals.
AB  - Acoustic backscattering measurements and associated scattering modeling were
      recently conducted on a type of benthic shelled animal that has a spiral form of
      shell (Littorina littorea). Benthic and planktonic shelled animals with this
      shape occur on the seafloor and in the water column, respectively, and can be a
      significant source of acoustic scattering in the ocean. Modeling of the
      scattering properties allows reverberation predictions to be made for sonar
      performance predictions as well as for detection and classification of animals
      for biological and ecological applications. The studies involved measurements
      over the frequency range 24 kHz to 1 MHz and all angles of orientation in as
      small as 1 degree increments. This substantial data set is quite revealing of the
      physics of the acoustic scattering by these complex shelled bodies and served as
      a basis for the modeling. Specifically, the resonance structure of the scattering
      was strongly dependent upon angle of orientation and could be traced to various
      types of rays (e.g., subsonic Lamb waves and rays entering the opercular
      opening). The data are analyzed in both the frequency and time domain (compressed
      pulse processing) so that dominant scattering mechanisms could be identified.
      Given the complexity of the animal body (irregular elastic shell with
      discontinuities), approximate scattering models are used with only the dominant
      scattering properties retained. Two models are applied to the data, both
      approximating the body as a deformed sphere: (1) an averaged form of the exact
      modal-series-based solution for the spherical shell, which is used to estimate
      the backscattering by a deformed shell averaged over all angles of orientation,
      and produces reasonably accurate predictions over all k1a(esr) (k1 is the
      acoustic wave number of the surrounding water and a(esr) is the equivalent
      spherical radius of the body), and (2) a ray-based formula which is used to
      estimate the scattering at fixed angle of orientation, but only for high
      k1a(esr). The ray-based model is an extension of a model recently developed for
      the shelled zooplankton Limacina retroversa that has a shape similar to that of
      the Littorina littorea but swims through the water [Stanton et al., J. Acoust.
      Soc. Am. 103, 236-253 (1998b)]. Applications of remote detection and
      classification of the seafloor and water column in the presence of shelled
      animals are discussed.

PMID- 10955619
TI  - On acoustic scattering by a shell-covered seafloor.
AB  - Acoustic scattering by the seafloor is sometimes influenced, if not dominated, by
      the presence of discrete volumetric objects such as shells. A series of
      measurements of target strength of a type of benthic shelled animal and
      associated scattering modeling have recently been completed (Stanton et al.,
      "Acoustic scattering by benthic and planktonic shelled animals," J. Acoust. Soc.
      Am., this issue). The results of that study are used herein to estimate the
      scattering by the seafloor with a covering of shells at high acoustic
      frequencies. A simple formulation is derived that expresses the area scattering
      strength of the seafloor in terms of the average reduced target strength or
      material properties of the discrete scatterers and their packing factor (where
      the reduced target strength is the target strength normalized by the geometric
      cross section of the scatterers and the averaging is done over orientation and/or
      a narrow range of size or frequency). The formula shows that, to first order, the
      backscattering at high acoustic frequencies by a layer of shells (or other
      discrete bodies such as rocks) depends principally upon material properties of
      the objects and packing factor and is independent of size and acoustic frequency.
      Estimates of area scattering strength using this formula and measured values of
      the target strength of shelled bodies from Stanton et al. (this issue) are close
      to or consistent with observed area scattering strengths due to shell-covered
      seafloors published in other papers.

PMID- 10955620
TI  - On the applicability of Kramers-Kronig relations for ultrasonic attenuation
      obeying a frequency power law
AB  - In the recent literature concern has been raised regarding the validity of
      Kramers-Kronig relations for media with ultrasonic attenuation obeying a
      frequency power law. It is demonstrated, however, that the Kramers-Kronig
      dispersion relations for application to these types of media are available. The
      developed dispersion relations are compared with measurements on several liquids,
      and agreement is found to better than 1 m/s over the experimentally available
      bandwidth. A discussion regarding the validity of these dispersion relations, in
      particular how the dispersion relations relate to the so-called Paley-Wiener
      conditions, forms the conclusion.

PMID- 10955621
TI  - Diffraction effects on bulk-wave ultrasonic velocity and attenuation measurements
AB  - The loss and phase advance due to diffraction are experimentally observed by
      measuring the amplitude and phase of radio frequency (rf) tone burst signals in
      the VHF range, in an ultrasonic transmission line consisting of a buffer rod with
      an ultrasonic transducer on one end, a couplant of water, and a solid specimen of
      synthetic silica glass. The measured results agree well with the calculated
      results from the exact integral expression of diffraction. The diffraction
      effects on the velocity and attenuation measured in this frequency range and
      their corrections are investigated to realize more accurate measurements. It is
      shown that attenuation measurements are influenced by diffraction losses and can
      be corrected by numerical calculations, and that velocity measurements are
      affected by the phase advance caused by diffraction. This investigation
      demonstrates that, in complex-mode velocity measurements, in which the velocity
      is determined from the measured phase of the signals, the true velocity at each
      frequency can be obtained by correction using the numerical calculation of
      diffraction. Based on this result, a new correction method in amplitude-mode
      velocity measurements is also proposed. In this new method, the velocity is
      determined from the intervals of interference output obtained by sweeping the
      ultrasonic frequency for the superposed signals generated by the double-pulse
      method. Velocity may be measured accurately at frequencies in the Fresnel region,
      and diffraction correction is essential to obtain highly accurate values with
      five significant figures or more.

PMID- 10955622
TI  - Elastic constants of an aluminum-alumina unidirectional composite
AB  - The five independent second-order elastic constants of a transversely isotropic
      aluminum/alumina fiber composite have been measured for the first time using a
      resonant ultrasound spectroscopy technique. These data were used to deduce the
      elastic constants and engineering moduli for off-axis loading conditions.

PMID- 10955623
TI  - Scattering-induced attenuation of an ultrasonic beam in austenitic steel
AB  - The scattering-induced attenuation coefficient of a beam of longitudinal waves
      propagating through an austenitic steel plate is measured as a function of the
      texture angle. The experimental data were obtained by mapping the incident and
      the transmitted ultrasonic field, and by evaluating the energy loss experienced
      by each plane wave component of the beam. Contrary to the behavior of data
      obtained by means of conventional techniques, that of the data reported in this
      work agrees qualitatively with the theoretical predictions. The reasons for the
      disagreement between theory and data obtained by means of conventional techniques
      are also discussed.

PMID- 10955624
TI  - The Huygens entrainment phenomenon and thermoacoustic engines
AB  - The earliest known reference to the mode-locking, or entrainment, of two
      maintained oscillators is Christiaan Huygens' description of two pendulum clocks
      "falling into synchrony" when hung on the same wall. We describe an analogous
      phenomenon in acoustics-the mode-locking of two thermoacoustic engines which have
      their cases rigidly welded together, but which are otherwise uncoupled. This
      "mass-coupling" might compete with acoustic coupling when the latter is used to
      enforce antiphase mode-locking in such engines, for vibration cancellation. A
      simple theory relating the phase difference between the engines in the locked
      state to the corresponding ratio of their pressure amplitudes is in excellent
      agreement with theory and numerical simulations. The theory's prediction relating
      the phase difference to the engines' natural frequency difference is
      qualitatively confirmed by experiment, despite larger experimental uncertainties.
      The mass coupling is relatively weak compared to the aforementioned acoustic
      coupling, and in general occurs in antiphase, so we conclude that mass coupling
      will not interfere with vibration cancellation by acoustic coupling in most
      circumstances.

PMID- 10955625
TI  - A new method for the absolute measurement of piezoelectric coefficients on thin
      polymer films
AB  - A new quasistatic method to measure piezoelectric coefficients on thin polymer
      films is presented. This method is based on a combined experimental/analytical
      approach, where small polymer samples (6 mm x 3 mm x 110 microm) are encapsulated
      in a soft silicone rubber and an electric field is applied across their thickness
      (3-direction). Strains are measured optically along three perpendicular
      directions using a laser Doppler vibrometer, and the experimental measurements
      are used in a Rayleigh-Ritz energy minimization procedure implemented
      symbolically in MATHCAD, which yields the absolute piezoelectric coefficients
      d(3ii). These measured coefficients are material properties of the polymer and do
      not depend on the specific boundary conditions of the problem. The validity of
      the method is established using the ATILA finite element code. Experimental
      values of d(311), d(322), and d(333) obtained for polyvinylidene fluoride (PVDF)
      at room temperature, in the frequency range 500-2000 Hz, are presented and
      compared with existing data; excellent agreement is found. The extension of the
      method to the determination of electrostrictive coefficients on soft polyurethane
      materials is introduced.

PMID- 10955626
TI  - Integrated photoelectric device made of a piezoelectric ceramic exhibiting
      pyroelectricity and an internal photoeffect
AB  - This paper reports on the preparation of a piezoelectric ceramic, which also
      exhibits pyroelectricity and an internal photoeffect. It then describes the
      design and trial production of a new integrated photoelectric device using this
      ceramic with a piezoelectric transformer, a solar cell, and an inverter.
      Important applications of this device are given.

PMID- 10955627
TI  - Investigation of active structural intensity control in finite beams: theory and
      experiment
AB  - An investigation of structural intensity control is presented in this paper. As
      opposed to previous work, the instantaneous intensity is completely taken into
      account in the control algorithm, i.e., all the terms are considered in the real
      time control process and, in particular, the evanescent waves are considered in
      this approach. A finite difference approach using five accelerometers is used as
      the sensing scheme. A feedforward filtered-X least mean square algorithm is
      adapted to this energy-based control problem, involving a nonpositive definite
      quadratic form in general. In this respect, the approach is limited to cases
      where the geometry is such that the intensity component will have the same sign
      for the control source and the primary disturbance. Results from numerical
      simulations are first presented to illustrate the benefit of using a cost
      function based on structural intensity. Experimental validation of the approach
      is conducted on a free-free beam covered with viscoelastic material. A comparison
      is made between classical acceleration control and structural intensity control
      and the performance of both approaches is presented. These results confirm that
      using intensity control allows the error sensors to be placed closer to the
      control source and the primary disturbance, while preserving a good control
      performance.

PMID- 10955628
TI  - Experimental study of sound propagation in a flexible duct
AB  - Propagation of sound in a flexible duct is investigated both theoretically and
      experimentally. Strong coupling of sound and flexural waves on the duct wall is
      found when the wall-to-air mass ratio is of the order of unity. The axial phase
      speed of sound approaches the in vacuo speed of flexural waves (subsonic in this
      case) at low frequencies. However, a speed higher than the isentropic sound speed
      in free space (340 m/s) is found beyond a critical frequency which is a function
      of the mass ratio. Experiments using a duct with a finite section of tensioned
      membrane are compared with the propagating modes pertaining to the infinite
      membrane model. Satisfactory quantitative agreement is obtained and the measured
      phase speed ranges from 8.3 to 1348 m/s. In the moderate frequency range, the
      theory predicts high spatial damping rate for the subsonic waves, which is
      consistent with the experimental observation that subsonic waves become
      increasingly undetectable as the frequency increases. Substantial sound
      reflection is observed at the interface between the rigid and the flexible
      segments of the duct without cross-section discontinuity, which, together with
      the high spatial damping, could form a basis for passive control of low-frequency
      duct noise.

PMID- 10955629
TI  - Sound propagation and speech transmission in a branching underground tunnel.
AB  - The characteristics of sound propagation and speech transmission along a tunnel
      with a "T" intersection were investigated. At receivers within sight of the sound
      source, low frequencies were mainly attenuated around the intersection than high
      frequencies. At receivers out of sight of the source, high frequencies were
      extensively attenuated. The overall pattern of sound attenuation along the
      different sections of tunnel, which was calculated by the conical beam method,
      agreed well with the measurements in this study. Numerical calculations of
      reflected and diffracted waves with minimum transmission paths in a two
      dimensional plane showed that reflected waves were the primary contributors to
      sound fields out of sight of the source. The articulation scores measured at
      receivers within sight of the source were high, and most of the confusion
      concerned syllables that could easily be misheard, even if there were a high
      signal-to-noise ratio. The types of syllable confusions observed at the receivers
      out of sight of the source appeared to have been caused by the greater
      deterioration in speech signals along this part of the tunnel, especially at high
      frequencies. The evaluation by rapid speech transmission indices (RASTI) appeared
      to be overestimated at the receivers out of sight of the source. Taking into
      account the early decay times of impulsive sound and the calculation procedures
      used in RASTI, it is concluded that speech intelligibility may not have been
      evaluated correctly by RASTI.

PMID- 10955630
TI  - From a profiled diffuser to an optimized absorber
AB  - The quadratic residue diffuser was originally designed for enhanced scattering.
      Subsequently, however, it has been found that these diffusers can also be
      designed to produce exceptional absorption. This paper looks into the absorption
      mechanism of the one-dimensional quadratic residue diffuser. A theory for
      enhanced absorption is presented. Corresponding experiments have also been done
      to verify the theory. The usefulness of a resistive layer at the well openings
      has been verified. A numerical optimization was performed to obtain a better
      depth sequence. The results clearly show that by arranging the depths of the
      wells properly in one period, the absorption is considerably better than that of
      a quadratic residue diffuser.

PMID- 10955631
TI  - On the combined effects of early- and late-arriving sound on spatial impression
      in concert halls.
AB  - This paper describes six new experiments involving subjective ratings of the
      listener envelopment, LEV, and the apparent source width, ASW, of simulated sound
      fields. Previous work has identified LEV and ASW as the principal components of
      spatial impression in concert halls and has shown that ASW is primarily
      influenced by the level of early lateral reflections and LEV by late-arriving
      lateral reflections. The new results in this paper show that LEV can result from
      nonlateral late-arriving sounds and demonstrate the conflicting effects of early-
      and late-arriving lateral sound on ASW and LEV when both are present, as would
      occur in real halls. While it is possible to create simulated sound fields with
      only either LEV or ASW, in typical concert halls, the balance between early- and
      late-arriving lateral sound will determine the relative importance of LEV and
      ASW. LEV and ASW are shown to be perceived when the critical components of the
      sound field are salient relative to other components. The results of the new
      subjective studies were used to estimate expected ASW and LEV in 16 halls. In
      these halls LEV is predicted to be the stronger component of spatial impression.

PMID- 10955632
TI  - Variation of measured sound speeds in gaseous and liquid air with temperature and
      pressure
AB  - Based on sound speeds in gaseous and liquid air measured by Younglove and
      Frederick [Int. J. Thermophys. 13(6), 1033-1041 (1992)], empirical equations for
      the computation of sound speeds in the above media at relatively smaller
      temperature and pressure ranges were derived. For gaseous air, over a temperature
      range from 200 to 300 K and pressure from 0.614 to 10.292 MPa, the maximum
      deviation between the measured sound speeds and those computed with the empirical
      equation is 56 ppm. For liquid air, over the ranges from 90 to 110 K for
      temperature and from 0.763 to 13.823 MPa for pressure, the corresponding
      deviation is 173 ppm.

PMID- 10955633
TI  - Medial efferent effects on auditory-nerve responses to tail-frequency tones II:
      alteration of phase.
AB  - It is often assumed that at frequencies in the tuning-curve tail there is a
      passive, constant coupling of basilar-membrane motion to inner hair cell (IHC)
      stereocilia. This paper shows changes in the phase of auditory-nerve-fiber (ANF)
      responses to tail-frequency tones and calls into question whether basilar
      membrane-to-IHC coupling is constant. In cat ANFs with characteristic frequencies
      > or = 10 kHz, efferent effects on the phase of ANF responses to tail-frequency
      tones were measured. Efferent stimulation caused substantial changes in ANF phase
      (deltaphi) (range -80 degrees to +60 degrees, average -15 degrees, a phase lag)
      with the largest changes at sound levels near threshold and 3-4 octaves below
      characteristic frequency (CF). At these tail frequencies, efferent stimulation
      had much less effect on the phase of the cochlear microphonic (CM) than on ANF
      phase. Thus, since CM is synchronous with basilar-membrane motion for low
      frequency stimuli in the cochlear base, the efferent-induced change in ANF phase
      is unlikely to be due entirely to a change in basilar-membrane phase. At tail
      frequencies, ANF phase changed with sound level (often by 90 degrees-180 degrees)
      and the deltaphi from a fiber was positively correlated with the slope of its
      phase-versus-sound-level function at the same frequency, as if deltaphi were
      caused by a 2-4 dB increase in sound level. This correlation suggests that the
      processes that produce the change in ANF phase with sound level at tail
      frequencies are also involved in producing deltaphi. It is hypothesized that both
      efferent stimulation and increases in sound level produce similar phase changes
      because they both produce a similar mix of cochlear vibrational modes.

PMID- 10955634
TI  - A high-precision magnetoencephalographic study of human auditory steady-state
      responses to amplitude-modulated tones.
AB  - The cerebral magnetic field of the auditory steady-state response (SSR) to
      sinusoidal amplitude-modulated (SAM) tones was recorded in healthy humans. The
      waveforms of underlying cortical source activity were calculated at multiples of
      the modulation frequency using the method of source space projection, which
      improved the signal-to-noise ratio (SNR) by a factor of 2 to 4. Since the complex
      amplitudes of the cortical source activity were independent of the sensor
      position in relation to the subject's head, a comparison of the results across
      experimental sessions was possible. The effect of modulation frequency on the
      amplitude and phase of the SSR was investigated at 30 different values between 10
      and 98 Hz. At modulation frequencies between 10 and 20 Hz the SNR of harmonics
      near 40 Hz were predominant over the fundamental SSR. Above 30 Hz the SSR showed
      an almost sinusoidal waveform with an amplitude maximum at 40 Hz. The amplitude
      decreased with increasing modulation frequency but was significantly different
      from the magnetoencephalographic (MEG) background activity up to 98 Hz. Phase
      response at the fundamental and first harmonic decreased monotonically with
      increasing modulation frequency. The group delay (apparent latency) showed peaks
      of 72 ms at 20 Hz, 48 ms at 40 Hz, and 26 ms at 80 Hz. The effects of stimulus
      intensity, modulation depth, and carrier frequency on amplitude and phase of the
      SSR were also investigated. The SSR amplitude decreased linearly when stimulus
      intensity or the modulation depth were decreased in logarithmic steps. SSR
      amplitude decreased by a factor of 3 when carrier frequency increased from 250 to
      4000 Hz. From the phase characteristics, time delays were found in the range of 0
      to 6 ms for stimulus intensity, modulation depth, and carrier frequency, which
      were maximal at low frequencies, low intensities, or maximal modulation depth.

PMID- 10955635
TI  - The perceptual tone/noise ratio of merged, iterated rippled noises with octave,
      harmonic, and nonharmonic delay ratios
AB  - The perceptual tone/noise ratio was measured for merged iterated ripple noise
      stimuli (IRNs) in which one of the individual IRNs always had a delay of 16 ms.
      The second IRN was chosen to create merged IRNs with single octave delay ratios
      (e.g., 16 ms:8 ms), double octave delay ratios (e.g., 16 ms:4 ms), harmonic delay
      ratios (e.g., 16 ms:12 ms), and nonharmonic delay ratios (e.g., 16 ms:3.9 ms).
      All stimuli were high-pass filtered at 800 Hz. The tone/noise ratio was
      significantly enhanced for the octave ratios, and there was a strong interaction
      between the single and double octave delay ratios and number of iterations. But,
      the perceptual tone/noise ratio for nonoctave ratios was determined solely by the
      number of iterations. The pattern of the results can be explained in terms of the
      height of the largest peak in the summary autocorrelogram [Meddis and Hewitt, J.
      Acoust. Soc. Am. 89, 2866-2882 (1991)] provided the model is modified to improve
      the simulation of the loss of phase locking.

PMID- 10955636
TI  - Pitch matches between unresolved complex tones differing by a single interpulse
      interval.
AB  - The experiment compared the pitches of complex tones consisting of unresolved
      harmonics. The fundamental frequency (F0) of the tones was 250 Hz and the
      harmonics were bandpass filtered between 5500 and 7500 Hz. Two 20-ms complex-tone
      bursts were presented, separated by a brief gap. The gap was an integer number of
      periods of the waveform: 0, 4, or 8 ms. The envelope phase of the second tone
      burst was shifted, such that the interpulse interval (IPI) across the gap was
      reduced or increased by 0.25 or 0.75 periods (1 or 3 ms). A "no shift" control
      was also included, where the IPI was held at an integer number of periods. Pitch
      matches were obtained by varying the F0 of a comparison tone with the same
      temporal parameters as the standard but without the shift. Relative to the no
      shift control, the variations in IPI produced substantial pitch shifts when there
      was no gap between the bursts, but little effect was seen for gaps of 4 or 8 ms.
      However, for some conditions with the same IPI in the shifted interval, an
      increase in the IPI of the comparison interval from 4 to 8 ms (gap increased from
      0 to 4 ms) changed the pitch match. The presence of a pitch shift suggests that
      the pitch mechanism is integrating information across the two tone bursts. It is
      argued that the results are consistent with a pitch mechanism employing a long
      integration time for continuous stimuli that is reset in response to temporal
      discontinuities. For a 250-Hz F0, an 8-ms IPI may be sufficient for resetting.
      Pitch models based on a spectral analysis of the simulated neural spike train, on
      an autocorrelation of the spike train, and on the mean rate of pitch pulses, all
      failed to account for the observed pitch matches.

PMID- 10955637
TI  - Effect of masker harmonicity on informational masking.
AB  - Detection thresholds for a tone in an unfamiliar tonal pattern can be greatly
      elevated under conditions of masker uncertainty [Neff and Green, Percept.
      Psychophys. 41, 409-415 (1987); Oh and Lutfi, J. Acoust. Soc. Am. 101, 3148
      (1997)]. The present experiment was undertaken to determine whether harmonicity
      of masker tones can reduce the detrimental effect of masker uncertainty.
      Inharmonic maskers were comprised of m=2-49 frequency components selected at
      random on each presentation within 100-10000 Hz, excluding frequencies between
      920-1080. Harmonic maskers were comprised of frequency components selected at
      random within this same range, but constrained to have a fundamental frequency of
      200 Hz. For inharmonic maskers the signal was a 1000-Hz tone. For harmonic
      maskers the signal was a tone whose frequency was either harmonically (1000 Hz)
      or inharmonically (1047 Hz) related to the masker. In all conditions the amount
      of masking was greatest for m = 20-40 components. At this point, harmonic maskers
      with harmonic signal produced an average of 9-12 dB less masking than inharmonic
      maskers. Harmonic maskers with inharmonic signal produced an average of 16-20 dB
      less masking.

PMID- 10955638
TI  - Neighboring spectral content influences vowel identification.
AB  - Four experiments explored the relative contributions of spectral content and
      phonetic labeling in effects of context on vowel perception. Two 10-step series
      of CVC syllables ([bVb] and [dVd]) varying acoustically in F2 midpoint frequency
      and varying perceptually in vowel height from [delta] to [epsilon] were
      synthesized. In a forced-choice identification task, listeners more often labeled
      vowels as [delta] in [dVd] context than in [bVb] context. To examine whether
      spectral content predicts this effect, nonspeech-speech hybrid series were
      created by appending 70-ms sine-wave glides following the trajectory of CVC F2's
      to 60-ms members of a steady-state vowel series varying in F2 frequency. In
      addition, a second hybrid series was created by appending constant-frequency sine
      wave tones equivalent in frequency to CVC F2 onset/offset frequencies. Vowels
      flanked by frequency-modulated glides or steady-state tones modeling [dVd] were
      more often labeled as [delta] than were the same vowels surrounded by nonspeech
      modeling [bVb]. These results suggest that spectral content is important in
      understanding vowel context effects. A final experiment tested whether spectral
      content can modulate vowel perception when phonetic labeling remains intact.
      Voiceless consonants, with lower-amplitude more-diffuse spectra, were found to
      exert less of an influence on vowel perception than do their voiced counterparts.
      The data are discussed in terms of a general perceptual account of context
      effects in speech perception.

PMID- 10955639
TI  - The influence of carrier level and frequency on modulation and beat-detection
      thresholds for sinusoidal carriers
AB  - This paper is concerned with modulation and beat detection for sinusoidal
      carriers. In the first experiment, temporal modulation transfer functions (TMTFs)
      were measured for carrier frequencies between 1 and 10 kHz. Modulation rates
      covered the range from 10 Hz to about the rate equaling the critical bandwidth at
      the carrier frequency. In experiment 2, TMTFs for three carrier frequencies were
      obtained as a function of the carrier level. In the final experiment, thresholds
      for the detection of either the lower or the upper modulation sideband (beat
      detection) were measured for "carrier" frequencies of 5 and 10 kHz, using the
      same range of modulation rates as in experiment 1. The TMTFs for carrier
      frequencies of 2 kHz and higher remained flat up to a modulation rate of about
      100-130 Hz and had similar values across carrier frequencies. For higher rates,
      modulation thresholds initially increased and then decreased rapidly, reflecting
      the subjects' ability to resolve the sidebands spectrally. Detection thresholds
      generally improved with increasing carrier level, but large variations in the
      exact level dependence were observed, across subjects as well as across carrier
      frequencies. For beat rates up to about 70 Hz (at 5 kHz) and 100 Hz (at 10 kHz),
      beat detection thresholds were the same for the upper and the lower sidebands and
      were about 6 dB higher than the level per sideband at the modulation-detection
      threshold. At higher rates the threshold for both sidebands increased, but the
      increase was larger for the lower sideband. This reflects an asymmetry in masking
      with more masking towards lower frequencies. Only at rates well beyond the
      maximum of the TMTF did detection for the lower sideband start to be better than
      that for the upper sideband. The asymmetry at intermediate frequency separations
      can be explained by assuming that detection always takes place in filters
      centered above the stimulus spectrum. The shape of the TMTF and the beat
      detection data reflects a limitation in resolving fast amplitude variations,
      which must occur central to the inner-ear filtering. Its characteristic resembles
      that of a first-order low-pass filter with a cutoff frequency of about 150 Hz.

PMID- 10955640
TI  - An analysis of quasi-frequency-modulated noise and random-sideband noise as
      comparisons for amplitude-modulated noise.
AB  - Experiments were performed to determine under what conditions quasi-frequency
      modulated (QFM) noise and random-sideband noise are suitable comparisons for AM
      noise in measuring a temporal modulation transfer function (TMTF). Thresholds
      were measured for discrimination of QFM from random-sideband noise and AM from
      QFM noise as a function of sideband separation. In the first experiment, the
      upper spectral edge of the noise stimuli was at 2400 Hz and the bandwidth was
      1600 Hz. For sideband separations up to 256 Hz, at threshold sideband levels for
      discriminating AM from QFM noise, QFM was indiscriminable from random-sideband
      noise. For the largest sideband separation used (512 Hz), listeners may have used
      within-stimulus envelope correlation in the QFM noise to discriminate it from the
      random-sideband noise. Results when stimulus bandwidth was varied suggest that
      listeners were able to use this cue when the carrier was wider than a critical
      band, and the sideband separation approached the carrier bandwidth. Within
      stimulus envelope correlation was also present in AM noise, and thus QFM noise
      was a suitable comparison because it made this cue unusable and forced listeners
      to use across-stimulus envelope differences. When the carrier bandwidth was less
      than a critical band or was wideband, QFM noise and random-sideband noise were
      equally suitable comparisons for AM noise. When discrimination thresholds for QFM
      and random-sideband noise were converted to modulation depth and modulation
      frequency, they were nearly identical to those for discrimination of AM from QFM
      noise, suggesting that listeners were using amplitude modulation cues in both
      cases.

PMID- 10955641
TI  - The effect of aging on horizontal plane sound localization.
AB  - An experiment was conducted to determine the effect of aging on sound
      localization. Seven groups of 16 subjects, aged 10-81 years, were tested. Sound
      localization was assessed using six different arrays of four or eight
      loudspeakers that surrounded the subject in the horizontal plane, at a distance
      of 1 m. For two 4-speaker arrays, one loudspeaker was positioned in each spatial
      quadrant, on either side of the midline or the interaural axis, respectively. For
      four 8-speaker arrays, two loudspeakers were positioned in each quadrant, one
      close to the midline and the second separated from the first by 15 degrees, 30
      degrees, 45 degrees, or 60 degrees. Three different 300-ms stimuli were
      localized: two one-third-octave noise bands, centered at 0.5 and 4 kHz, and
      broadband noise. The stimulus level (75 dB SPL) was well above hearing threshold
      for all subjects tested. Over the age range studied, percent-correct sound-source
      identification judgments decreased by 12%-15%. Performance decrements were
      apparent as early as the third decade of life. Broadband noise was easiest to
      localize (both binaural and spectral cues were available), and the 0.5-kHz noise
      band, the most difficult to localize (primarily interaural temporal difference
      cue available). Accuracy was relatively higher in front of than behind the head,
      and errors were largely front/back mirror image reversals. A left-sided
      superiority was evident until the fifth decade of life. The results support the
      conclusions that the processing of spectral information becomes progressively
      less efficient with aging, and is generally worse for sources on the right side
      of space.

PMID- 10955642
TI  - Binaural effects in center-frequency modulation detection interference for vowel
      formants.
AB  - The detection of slow (5 Hz) center-frequency modulations of formants (signals)
      can be impaired by the simultaneous presentation of off-frequency modulated
      formants (maskers) to the same ear [J. Lyzenga and R. P. Carlyon, J. Acoust. Soc.
      Am. 105, 2792-2806 (1999)]. In the present study we examine this "formant
      frequency modulation detection interference (FMDI)" for various binaural masker
      presentation schemes. Signals and maskers were formantlike complex tones,
      centered around 1500 and 3000 Hz, respectively. Fundamentals of 80 and 240 Hz
      were used. The signals were presented to the right ear. The maskers were
      presented either to the right, the left, or to both ears, and they were either
      unmodulated or modulated at a slow rate (10 Hz). They had the same fundamental as
      the signals. Hardly any interference was found for the unmodulated maskers. For
      modulated maskers, the amount of FMDI depended strongly on the binaural masker
      presentation scheme. Substantial interference was found for the ipsilateral
      maskers. Interference was smaller for the contralateral maskers. In both cases
      the FMDI increased with increasing masker level. Substantial interference was
      also found for the binaural maskers. Imposing different interaural time and level
      differences (ITDs and ILDs) on maskers and signals did not affect FMDI. The same
      was true for the ITD condition when the maskers had different fundamentals than
      the signals, though FMDI was slightly smaller here. The amount of interference
      for the binaural maskers was roughly equal to that of the corresponding monaural
      masker with the largest effect. The data could not be described accurately using
      a model based on the loudness of the maskers. On the other hand, they were well
      described by a model in which the amount of FMDI was predicted from a "weighted
      combination" of the monaural masker levels.

PMID- 10955643
TI  - Intensity discrimination and detection of amplitude modulation in electric
      hearing.
AB  - Wojtczak and Viemeister [J. Acoust. Soc. Am. 106, 1917-1924 (1999)] demonstrated
      a close relationship between intensity difference limens (DLs) and 4-Hz amplitude
      modulation (AM) detection thresholds in normal-hearing acoustic listeners. The
      present study demonstrates a similar relationship between intensity DLs and AM
      detection thresholds in cochlear-implant listeners, for gated stimuli. This
      suggests that acoustic and cochlear-implant listeners make use of a similar
      decision variable to perform intensity discrimination and modulation detection
      tasks. It can be shown that the absence of compression in electric hearing does
      not preclude this possibility.

PMID- 10955644
TI  - A cross-language study of the identification of non-native nasal consonants
      varying in place of articulation.
AB  - Seven listener groups, varying in terms of the nasal consonant inventory of their
      native language, orthographically labeled and rated a set of naturally produced
      non-native nasal consonants varying in place of articulation. The seven listener
      groups included speakers of Malayalam, Marathi, Punjabi, Tamil, Oriya, Bengali,
      and American English. The stimulus set included bilabial, dental, alveolar, and
      retroflex nasals from Malayalam, Marathi, and Oriya. The stimulus set and nasal
      consonant inventories of the seven listener groups were described by both
      phonemic and allophonic representations. The study was designed to determine the
      extent to which phonemic and allophonic representations of perceptual categories
      can be used to predict a listener group's identification of non-native sounds.
      The results of the experiment showed that allophonic representations were more
      successful in predicting the native category that listeners used to label a non
      native sound in a majority of trials. However, both representations frequently
      failed to accurately predict the goodness of fit between a non-native sound and a
      perceptual category. The results demonstrate that the labeling and rating of non
      native stimuli were conditioned by a degree of language-specific phonetic detail
      that corresponds to perceptually relevant cues to native language contrasts.

PMID- 10955645
TI  - Tests of auditory-visual integration efficiency within the framework of the fuzzy
      logical model of perception.
AB  - The fuzzy logical model of perception [FLMP, Massaro, Perceiving Talking Faces:
      From Speech Perception to a Behavioral Principle (MIT Press, Cambridge, MA,
      1998)] has been extremely successful at describing performance across a wide
      range of ecological domains as well as for a broad spectrum of individuals.
      Because the model predicts optimal or maximally efficient integration, an
      important issue is whether this is the case for most individuals. Three databases
      are evaluated to determine to what extent a significant quantitative improvement
      in predictive ability can be obtained if integration is assumed to be somewhat
      inefficient. For the most part, there were no significant signs of inefficient
      integration. The previous differences found by Grant and Seitz [J. Acoust. Soc.
      Am. 104, 2438-2450 (1998)] must be due to their measures of efficiency, which
      appear to be invalid and/or conflate information with integration efficiency.
      Finally, the descriptive ability of the FLMP is shown to be theoretically
      informative and not simply the model's ability to describe any possible outcome.

PMID- 10955646
TI  - The effect of parametric variations of cochlear implant processors on speech
      understanding.
AB  - This study investigated the effect of five speech processing parameters,
      currently employed in cochlear implant processors, on speech understanding.
      Experiment 1 examined speech recognition as a function of stimulation rate in six
      Med-E1/CIS-Link cochlear implant listeners. Results showed that higher
      stimulation rates (2100 pulses/s) produced a significantly higher performance on
      word and consonant recognition than lower stimulation rates (<800 pulses/s). The
      effect of stimulation rate on consonant recognition was highly dependent on the
      vowel context. The largest benefit was noted for consonants in the /uCu/ and
      /iCi/ contexts, while the smallest benefit was noted for consonants in the /aCa/
      context. This finding suggests that the /aCa/ consonant test, which is widely
      used today, is not sensitive enough to parametric variations of implant
      processors. Experiment 2 examined vowel and consonant recognition as a function
      of pulse width for low-rate (400 and 800 pps) implementations of the CIS
      strategy. For the 400-pps condition, wider pulse widths (208 micros/phase)
      produced significantly higher performance on consonant recognition than shorter
      pulse widths (40 micros/phase). Experiments 3-5 examined vowel and consonant
      recognition as a function of the filter overlap in the analysis filters, shape of
      the amplitude mapping function, and signal bandwidth. Results showed that the
      amount of filter overlap (ranging from -20 to -60 dB/oct) and the signal
      bandwidth (ranging from 6.7 to 9.9 kHz) had no effect on phoneme recognition. The
      shape of the amplitude mapping functions (ranging from strongly compressive to
      weakly compressive) had only a minor effect on performance, with the lowest
      performance obtained for nearly linear mapping functions. Of the five speech
      processing parameters examined in this study, the pulse rate and the pulse width
      had the largest (positive) effect on speech recognition. For a fixed pulse width,
      higher rates (2100 pps) of stimulation provided a significantly better
      performance on word recognition than lower rates (<800 pps) of stimulation. High
      performance was also achieved by jointly varying the pulse rate and pulse width.
      The above results indicate that audiologists can optimize the implant listener's
      performance either by increasing the pulse rate or by jointly varying the pulse
      rate and pulse width.

PMID- 10955647
TI  - Vibrational mode shapes in Caribbean steelpans. I. Tenor and double second.
AB  - Vibrational mode shapes have been studied in several tenor (soprano range) and
      double-second (alto range) steelpans by three well-known makers. Normal modes are
      determined from operating deflection shapes recorded by means of electronic TV
      holography. Vibrational modes of the various note areas are designated by the
      number of radial and circumferential nodal lines. Tuners generally tune one mode
      an octave above the fundamental and, if possible, a third mode is tuned either a
      twelfth or two octaves above the fundamental. Note dimensions follow an
      approximate scaling law L=Kf(213), and the larger note areas can be roughly
      modeled as rectangular plates with simply supported edges. Modal shapes in the
      skirt correspond to standing bending waves propagating around the ring.

PMID- 10955648
TI  - Broadband time-domain reflectometry measurement of attenuation and phase velocity
      in highly attenuating suspensions with application to the ultrasound contrast
      medium Albunex.
AB  - We describe a technique for broadband measurements of the attenuation coefficient
      and phase velocity of highly attenuating liquid suspensions. To validate the
      technique we apply it to the ultrasound contrast agent Albunex at concentrations
      ranging from 0.69 x 10(6) particles/mL to 364 x 10(6) particles/mL. These
      longitudinal wave measurements were performed on Albunex suspensions maintained
      at 37 degrees C in a special time-domain reflectometer designed and constructed
      in our laboratory. The frequency-dependent attenuation coefficients and phase
      velocities obtained in the reflectometer are compared to broadband through
      transmission measurements of these same quantities, which were also performed in
      our laboratory. Although comparison data between the two techniques are only
      available at lower concentrations, the agreement is quite good and serves to
      validate the methods described in this paper.

PMID- 10955649
TI  - A class of chaotic bird calls?
AB  - Evidence is presented that the basic vocalized sound produced by some cockatoos,
      specifically the Australian sulfur-crested cockatoo (Cacatua galerita) and the
      gang-gang cockatoo (Callocephalon fimbriatum), has a chaotic acoustic structure
      rather than the harmonic structure characteristic of most birdsongs. These
      findings support those of Fee et al. [Nature (London) 395(3), 67-71 (1999)] on
      nonlinear period-doubling transitions in the song of the zebra finch (Taeniopygia
      guttata). It is suggested that syllables with chaotic structure may be a feature
      of the songs of many birds.

PMID- 10955650
TI  - Simulation of circular array ultrasound transducers for intravascular
      applications.
AB  - The beam shape of a circular array transducer that is commonly used in
      intravascular ultrasound catheters was investigated in linear mode of operation.
      For this use, a simulation program which can simulate the radio frequency (rf)
      response of a number of scatterers has been developed. The program is based on
      the impulse response method, which is implemented in the frequency domain. Due to
      the unusual geometry of the transducer, the far field gets peculiarly shaped for
      large apertures. Instead of having a far field with its maximum intensity in a
      single lobe on the acoustical axis, the far field splits up into a dual-lobe far
      field with maximum intensity in two lobes off the acoustical axis. A formula is
      derived that predicts the occurrence of these beam shapes.

PMID- 10955651
TI  - Foliage echoes: a probe into the ecological acoustics of bat echolocation.
AB  - The research reported here aims at understanding the biosonar system of bats
      based on the properties of its natural inputs (ecological acoustics). Echoes from
      foliages are studied as examples of ubiquitous, natural targets. The echo
      properties and their qualitative relationship to plant architecture are
      described. The echoes were found to be profoundly stochastic and in general
      neither Gaussian nor stationary. Consequently, features useful for discrimination
      of such target classes will be confined to estimated random process parameters.
      Several such statistical signal features which are sufficiently invariant to
      allow a classification of the used example plants were identified: the
      characteristic exponent and the dispersion of an alpha-stable model for the
      amplitude distribution, a crest factor defined as the ratio of maximum squared
      amplitude and signal energy, the dispersion of the first threshold passage
      distribution, the structure of the correlation matrix, and a nonstationarity in
      sound channel gain. Discrimination error probability could be reduced by
      combining features pairwise. The best combination was the crest factor and the
      correlation coefficient of a log-linear model of the time-variant sound channel
      gain; it yielded an estimated Bayes risk of 6.9% for data pooled from different
      views.

PMID- 10955652
TI  - About a double-body immersion horn system to be used for quantitative
      sonochemical studies
AB  - The majority of quantitative sonochemical studies in the 20-100-kHz frequency
      range are performed by using an immersion horn system. The new system described
      in this letter consists of a double immersion horn acted on by a single pair of
      piezoelectric ceramics. This instrument is well adapted to the quantitative
      measure of effects, i.e., variations in the rate constant of a specific reaction
      associated to the change of an experimental parameter. The gas effect, obtained
      by comparing the rate of a reaction under air and under argon, illustrates the
      efficiency of the system.

PMID- 10955653
TI  - Generalized thermoelastic waves in homogeneous isotropic plates
AB  - The propagation of thermoelastic waves in homogeneous isotropic plate subjected
      to stress-free and rigid insulated and isothermal conditions is investigated in
      the context of conventional coupled thermoelasticity (CT), Lord-Shulman (LS),
      Green-Lindsay (GL), and Green-Nagdhi (GN) theories of thermoelasticity. Secular
      equations for the plate in closed form and isolated mathematical conditions for
      symmetric and skew-symmetric wave mode propagation in completely separate terms
      are derived. It is shown that the motion for SH modes gets decoupled from the
      rest of the motion and remains unaffected due to thermo-mechanical coupling and
      thermal relaxation effects. The phase velocities for SH modes have also been
      obtained. The results for coupled and uncoupled theories of thermoelasticity have
      been obtained as particular cases from the derived secular equations. At short
      wavelength limits the secular equations for symmetric and skew-symmetric waves in
      a stress-free insulated and isothermal plate reduce to Rayleigh surface waves
      frequency equations. Finally, the numerical solution is carried out for aluminum
      epoxy composite material and the dispersion curves for symmetric and skew
      symmetric wave modes are presented to illustrate and compare the theoretical
      results.

PMID- 10955654
TI  - The risk profile of trabecular aspiration versus trabeculectomy in glaucoma
      triple procedure.
AB  - OBJECTIVE: This study was set up to establish the relative safety and
      effectiveness of trabecular aspiration in combination with phacoemulsification
      and intraocular lens (IOL) implantation (phacoaspiration) for decreasing
      intraocular pressure (IOP), and to compare the outcome of this method of
      treatment with that of standard filtering glaucoma triple procedure (phaco-trab).
      STUDY DESIGN: Prospective, randomized study. PARTICIPANTS: The study consisted of
      40 eyes of 40 patients with uncontrolled exfoliation glaucoma without a history
      of previous intra- or extraocular surgery and in need of cataract surgery.
      INTERVENTION: Temporal clear corneal phacoemulsification and foldable IOL
      implantation was performed in all eyes. In the phaco-aspiration group, trabecular
      aspiration was performed with a suction force of 100-200 mmHg under light tissue
      instrument contact using a modified intraocular aspiration probe. A modified
      Cairns-type trabeculectomy without adjunctive antimetabolites was performed
      superiorly in the phaco-trab eyes after IOL implantation. MAIN OUTCOME MEASURES:
      The surgical outcome was assessed in terms of IOP change, need for adjunctive
      glaucoma medication, visual acuity outcome, and incidence of complications.
      RESULTS: At 1 year after combined surgery, mean (+/-SD) IOP and number of
      glaucoma medi- cation were 19.5+/-2.7 mmHg and 0.6+/-0.5 in the phaco-aspiration
      group, compared with 17.5+/-2.4 mmHg and 0.3+/-0.4 in the phaco-trab group.
      Hyphema (38%) and ocular hypotony (14%) were observed in the phaco-trab group
      only, whereas blood reflux (52%) and descemetolyses (23%) were seen exclusively
      in the phaco-aspiration group. CONCLUSION: In exfoliative eyes, trabecular
      aspiration in combination with phacoemulsification and IOL implantation is less
      effective in reducing postoperative IOP and number of glaucoma medications than
      the standard filtering glaucoma triple procedure. The risk profile, however,
      appears to be more favorable in the phaco-aspiration-treated eyes than in the
      phaco-trab group. Trabecular aspiration in glaucoma triple procedure could serve
      as a possible treatment of choice for exfoliative eyes with coexisting cataract
      and glaucoma.

PMID- 10955655
TI  - A novel PAX6 gene mutation (P118R) in a family with congenital nystagmus
      associated with a variant form of aniridia.
AB  - BACKGROUND: A variety of PAX6 gene mutations were identified in patients with
      aniridia and/or allied ocular dysgenesis such as keratopathy, Peters' anomaly,
      foveal hypoplasia, and nystagmus. To scrutinize the etiology of a four-generation
      Japanese family with autosomal dominant nystagmus associated with anterior and
      posterior segment anomalies, the PAX6 gene was examined. PATIENTS AND METHODS: A
      Japanese family showed a variant aniridia phenotype in four successive
      generations. Affected individuals had congenital nystagmus, microcornea with
      shortened axial length, superficial peripheral corneal opacification with pannus
      formation, dislocated pupil, and foveal hypoplasia. Analysis of the PAX6 gene
      mutation was performed in affected and unaffected individuals. RESULTS: A novel
      missense mutation in the PAX6 gene was found in all affected individuals
      examined, but neither in unaffected individuals nor in unrelated healthy
      individuals. This mutation predicted a proline to arginine change at codon 118
      (P118R) in the paired domain of PAX6 protein. CONCLUSION: The reported family
      illustrates that mutations in the PAX6 gene, in particular missense mutations,
      may manifest atypical clinical expression or forme fruste of aniridia.

PMID- 10955656
TI  - Confocal laser scanning fluorescence topography: a new method for three
      dimensional functional imaging of vascular structures.
AB  - Three-dimensional topography of perfused vascular structures is possible via
      confocal laser scanning of intravascular fluorescence. The lateral resolution is
      given by the spot size of the scanning laser beam (optimally 10 microm at the
      retina). The axial resolution, however, depends on the accuracy of detection of
      the surface of the fluorescent structure, which is typically one order of
      magnitude higher (30 microm at the retina) than the confocal resolution. The
      vascular structure is stained with an appropriate fluorescent dye prior to the
      investigation using standard systemic dye injection. Confocal scanning of the
      fluorescence in planes of different depths within the vascular structure under
      investigation leads to a three-dimensional data set. Signal processing includes
      passive eye tracking, lateral averaging and axial determination of the surface of
      the fluorescent structure. The potential of this new technique is demonstrated by
      showing the topography of physiological vessel structures as well as of selected
      vascular diseases such as cone dystrophy, RPE detachment, choroidal haemangioma
      and retinal laser coagulation. Confocal laser angioscopic fluorescence topography
      (CLAFT) measures the three-dimensional surface structure of functional (perfused)
      vasculature and surrounding leakage. CLAFT may help to diagnose and quantify
      status and time course of vascular diseases.

PMID- 10955657
TI  - Lack of correlation between visual acuity and fixation stability after
      photocoagulation for diabetic maculopathy.
AB  - PURPOSE: To study the correlation between changes in visual acuity and changes in
      fixation stability after retinal photocoagulation for diabetic maculopathy.
      MATERIAL: Twenty-four patients with diabetic maculopathy and visual acuity (VA)
      ranging between 0.05-0.77 were studied at baseline and 1, 3, 6 and 12 months
      after retinal photocoagulation. Fixational eye movements were quantified from
      video recordings of the ocular fundus obtained with the Rodenstock scanning laser
      ophthalmoscope. RESULTS: No correlation was found between the changes in the
      quantitative measures of the fixational eye movements (amplitude and retinal area
      of fixation) and the changes in VA 12 months after retinal photocoagulation.
      Three patients all with VA<0.31 at baseline had the fixation centre located more
      than 3 deg from the centre of the foveal avascular zone (FAZ) at one or more of
      the follow-up examinations, and one of these patients used three different
      locations of fixations during the follow-up period. CONCLUSION: Changes in
      fixation stability after retinal photocoagulation are complex but not related to
      changes in visual acuity.

PMID- 10955658
TI  - The relationship between total tear protein concentrations determined by
      different methods and standards.
AB  - BACKGROUND: It is known that the values of total protein concentration (TPC) of
      human tears obtained by different methods/standards vary considerably. The
      variations are due to differences in reactivity of proteins to the methods used.
      The aim of this study was to investigate the relationships and agreements between
      TPC values obtained by different methods/standards. METHODS: Two experiments were
      conducted. In experiment 1, 30 normal subjects were recruited and their TPC were
      determined by the Bradford and the modified Lowry methods, with bovine serum
      albumin and bovine immunoglobulin G as standards. The relationships (equations)
      between TPC values obtained by different methods/standards were determined. In
      experiment 2, another 15 normal subjects were recruited and the TPC were measured
      as in experiment 1. Measured values of TPC using different methods/standards were
      compared with their respective values calculated from the equations defined in
      experiment 1. The agreement and the reliability between the measured and the
      calculated values were investigated. RESULTS: Experiment 1 showed that the TPC
      obtained by different methods/standards were strongly correlated to one another,
      and their relationships can be defined by linear equations. In experiment 2, the
      measured and the calculated values, using the equations defined in experiment 1,
      showed good agreement and reliability. This indicates that TPC obtained by one
      method/standard can be used to estimate the value(s) that would be obtained if
      another method/standard were used using the equation(s) found in experiment 1.
      CONCLUSION: The correlations between TPC values obtained by different
      methods/standards were strong. Our results also indicated good agreement and
      reliability between measured and calculated TPC values. Therefore, values
      obtained by different methods/standards are interchangeable using the appropriate
      equations.

PMID- 10955659
TI  - Visual and anatomical success with short-term macular tamponade and autologous
      platelet concentrate.
AB  - BACKGROUND: This study aimed to determine whether, in eyes treated for macular
      hole by vitrectomy and autologous platelet injection, short-term tamponade with
      SF6 gas was as effective as longer tamponade with C3F8 gas. METHODS: Patients in
      group 1 (n=31) had vitrectomy, injection of platelet concentrate, and 16% C3F8
      gas/air exchange. Patients in group 2 (n=31) were similarly treated, except that
      23% SF6 gas was used. Group 1 patients were required to posture prone for 2-4
      weeks, group 2 for 6 days. RESULTS: All patients had 3 months' follow-up.
      Postoperatively, visual acuity improved faster in group 2. However, the final
      mean improvement in logMAR acuity was similar in both groups. Intraocular
      pressure (IOP) spikes occurred in 12 patients in group 2 and in 17 patients in
      group 1. Posterior subcapsular cataract (PSCC) occurred in 55% of cases in group
      1 and in just 37% in group 2. The rate of anatomical success in group 1 was
      96.7%, and in group 2, 93.5% (P=1.0). CONCLUSIONS: The combination of SF6 gas,
      platelet concentrate, and short-term prone posturing gave a degree of anatomical
      and visual success comparable to that of the group which had longer tamponade.
      Although no differences were statistically significant, several trends did
      emerge; in group 2, patients recovered visual acuity faster, had fewer IOP
      spikes, and there were fewer cases of PSCC formation.

PMID- 10955660
TI  - Effects of peroxynitrite on rabbit cornea.
AB  - BACKGROUND: Nitric oxide (NO) reacts rapidly with the superoxide anion to
      generate peroxynitrite, which has been found in the aqueous humor in eyes with
      uveitis. We evaluated the functional and anatomic effects of peroxynitrite on
      rabbit cornea. METHODS: One eye of each rabbit received an anterior chamber
      injection of 3-morpholinosydonimine N-ethylcarbamide (SIN-1), which
      simultaneously generates both NO and the superoxide anion. The corneal thickness
      was measured using an ultrasonic pachymeter before and after the injection. The
      eyes were fixed and the corneal specimens were prepared for electron microscopy.
      RESULTS: Anterior chamber injections of SIN-1 caused a significant increase in
      the corneal thickness (25.1+/-3.0 microm) 30 min after injection. Transmission
      electron microscopy showed swollen mitochondria and large vacuoles in the
      cytoplasm, and scanning electron microscopy revealed obscuring of the mosaic
      pattern by increased ruffling of endothelial cell surface and borders.
      CONCLUSION: The results suggest that peroxynitrite generated in the aqueous humor
      may cause corneal endothelial cell damage, which leads to transient corneal
      edema.

PMID- 10955661
TI  - MHC expression in fragment and full-thickness allogeneic embryonic retinal
      transplants.
AB  - BACKGROUND: The study was carried out to evaluate the expression of major
      histocompatibility complex (MHC) molecules in retinal transplants with different
      tissue integrity. METHODS: Twelve adult rabbits received an allogeneic subretinal
      neuroretinal transplant, in the form of either fragmented embryonic cells or a
      complete full-thickness embryonic retina. A controlled transvitreal approach was
      used for both transplantation types. The grafts were examined histologically
      after 31 or 49 days with hematoxylin and eosin staining and immunohistochemical
      analysis of MHC class I and class II expression. RESULTS: All five fragment
      transplants developed into rosettes. Two of them displayed MHC class I-labeled
      cells, and four MHC class II-labeled cells. The cells were concentrated on the
      scleral side of the graft, and there was also a marked increase of labeled cells
      in the choroid. MHC labeling was often associated with defects in the retinal
      pigment epithelium. Six of the seven full-thickness grafts displayed a laminated
      morphology with well-developed retinal layers. The seventh consisted of rosettes.
      None of these grafts displayed MHC class I- or class II-labeled cells.
      CONCLUSIONS: The findings suggest that host immune response against fragmented
      and intact neuroretinal grafts is different, indicating tissue integrity as one
      factor affecting graft-host immune interactions. The absence of immune response
      in full-thickness grafts is encouraging and important in the struggle to find
      therapies for retinal degenerative disease.

PMID- 10955662
TI  - Selective photoreceptor damage in albino rats using continuous blue light. A
      protocol useful for retinal degeneration and transplantation research.
AB  - PURPOSE: To develop a retinal degeneration model with selective photoreceptor
      loss and RPE sparing, to be used as recipient for evaluating retinal transplants.
      METHODS: Albino rats were exposed to blue light, continuously, for 1-7 days (24
      168 h) in a specially designed cage. Eyes were histologically analyzed at periods
      between 2 h and 8 months after the light exposure. Electroretinograms (ERGs) were
      recorded from some rats at 12-216 days after exposure. Using behavioral methods,
      visual thresholds of some rats were determined before exposure and re-measured
      between 18 and 52 days following exposure. RESULTS: Apoptotic nuclei appeared
      exclusively in the photoreceptor layer after 1-5 days exposure to blue light.
      Light microscopy revealed that 2-4 days of light exposure reduced the outer
      nuclear layer (normally eight to ten rows) to 1 row of cells in the central
      retina and to two to three rows in the periphery, both in the superior and the
      inferior retina. Average ERG a- and b-wave amplitudes of light-damaged rats were
      both reduced by about 98%. Visual performance in the behavioral test was
      substantially impaired. CONCLUSIONS: Continuous exposure of albino rats to
      moderate blue light for 2-5 days selectively eliminates most of the
      photoreceptors while leaving the RPE initially intact.

PMID- 10955663
TI  - Quantitative analysis of subretinal injections in the rat.
AB  - BACKGROUND: Experimental therapeutic approaches to retinal degenerations often
      require the subretinal injection of a therapeutic agent. The injected volume and
      the age of the animal can influence the proportion of the retinal surface
      affected by the subretinal injection. We have investigated the quantitative
      effect of a single injection in the subretinal space. METHODS: Normal and Royal
      College of Surgeons rats aged 1 week, 3 weeks or 2 months received subretinal
      transscleral injections of 1, 3, 5 or 10 microl China ink. After 24 h, animals
      were killed, injected eyes were enucleated and fixated, and the retinas
      flattened. An image analyzing program was used to measure the total retinal
      surface and the retinal surface affected by the dye. RESULTS: The mean retinal
      surface affected by the injection ranged from 5.24+/-2.76 mm2 to 14.8+/-2.3 mm2,
      depending on animal age and injected volume. The injection affected 8.79+/-0.89
      to 36.9+/-8.13% of total retinal surface. There was no statistically significant
      difference between normal and Royal College of Surgeons rats. Intravitreal
      leakage of the dye was more frequent with increasing injection volumes.
      CONCLUSION: The retinal surface affected by a single subretinal injection
      increases with the injected volume, but this increase is not proportional. Higher
      volumes lead to a loss of injected solution, either in the vitreous body or
      through the sclerotomy. In 2-month-old rats, a 3-microl subretinal injection
      appears to have the best reproducibility, with 20-30% of retinal surface covered
      by the injected dye.

PMID- 10955664
TI  - Retinal abnormalities associated with a mutation of the nucleotide 683 in von
      Hippel-Lindau disease.
AB  - BACKGROUND: von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome in
      which affected individuals are at risk of developing tumors in multiple organs,
      including eyes, cerebellum, spinal cord, kidneys, inner ear, adrenal glands and
      pancreas. METHODS: We performed a fundus examination and fluorescein and
      indocyanine green (ICG) angiography in both eyes of a young woman affected by VHL
      with bilateral pheochromocytoma, retinal angioma, retinal microaneurysms and
      unusual alterations of the deep retinal layers. A molecular analysis of the VHL
      gene was carried out. RESULTS: Ophthalmoscopy disclosed in her right eye a small
      retinal hemangioma, some microaneurysms in both eyes at the posterior pole and
      multiple, small, whitish, dome-shaped lesions scattered in the retinal pigment
      epithelium (RPE) of the posterior retina. Fluorescein angiograms revealed in the
      early phase multiple hyperfluorescent spots that showed progressive discoloration
      in the late phase of angiography. Some of these spots were ophthalmoscopically
      undetectable. The late phase of ICG angiography showed some small
      hyperfluorescent points located at the level of the RPE, and some of them
      corresponded to the hyperfluorescent spots seen on fluorescein angiography. The
      molecular analysis revealed the presence of a "missense" mutation of the VHL gene
      at nucleotide 683. CONCLUSIONS: Alterations in the RPE have never been observed
      in the VHL syndrome. We describe an unusual case of VHL with a capillary
      hemangioma associated to diffuse alterations with the RPE of the posterior
      retina. The possibility exists that these lesions form part of the eye
      modifications in VHL.

PMID- 10955665
TI  - Retinal pigment epithelial tear and extensive exudative retinal detachment
      following blunt trauma.
AB  - BACKGROUND: A peripheral retinal pigment epithelial tear and an extensive
      exudative retinal detachment caused by choroidal leakage from the denuded Bruch's
      membrane are extremely rare. A peripheral retinal pigment epithelial tear has not
      been reported in an eye with retinochoroidal folds after blunt ocular trauma.
      METHODS: Case report. RESULTS: The course of a large nasal peripheral retinal
      pigment epithelial tear that occurred after blunt ocular trauma in a patient with
      retinochoroidal folds was followed. The inferior retinal detachment caused by
      leakage from the denuded Bruch's membrane following the development of the tear
      gradually worsened. Initial treatment with cryotherapy was ineffective, but the
      retinal detachment eventually resolved after the patient underwent sclerectomy
      and sclerostomy. CONCLUSION: A large peripheral retinal pigment epithelial tear
      can occur in patients with retinochoroidal folds following blunt ocular trauma,
      and extensive retinal detachment can be induced. Sclerectomy and sclerostomy can
      be beneficial in patients with an extensive exudative retinal detachment caused
      by choroidal leakage from the denuded Bruch's membrane.

PMID- 10955666
TI  - Indocyanine green angiographic findings in diffuse choroidal hemangioma
      associated with Sturge-Weber syndrome.
AB  - PURPOSE: To analyze indocyanine green angiography (ICGA) features in one case of
      diffuse choroidal hemangioma associated with Sturge-Weber syndrome. METHODS:
      Color fundus photography, fluorescein angiography (FA) and ICGA were performed in
      a patient with diffuse choroidal hemangioma associated with Sturge-Weber
      syndrome. RESULTS: The diffuse choroidal hemangioma was not identified by FA.
      ICGA revealed that the vascular tissue of the diffuse hemangioma filled rapidly
      with dye during the arterial phase of the choroidal angiogram; copious dye
      leakage appeared early and persisted into the late phase of angiography. Late
      "wash-out" phenomenon was not observed 30 minutes after dye injection. Sectors of
      reduced choroidal perfusion in the upper or lower half of the midperiphery were
      present. CONCLUSION: ICGA may be an important and sensitive technique in
      detecting the diffuse choroidal hemangioma associated with Sturge-Weber syndrome.

PMID- 10955667
TI  - Bypass-surgery and coil-embolisation in the treatment of cerebral giant
      aneurysms.
AB  - OBJECTIVE: Operative clipping is the most effective method in the treatment of
      cerebral giant aneurysms. But about 50% of all giant aneurysms are treatable this
      way. We want to report about eight patients with giant cerebral aneurysms, which
      were in our opinion "unclippable" without causing ischaemia in depending brain
      areas. METHODS: We describe eight cases of giant aneurysms of the pericallosal
      artery (n = 1) the middle cerebral artery (n = 3), the basilar tip (n = 3) and of
      the upper part of the basilar artery (n = 1). One patient with an aneurysm of the
      pericallosal artery was treated with an extra-intracranial saphenous vein bypass
      saphenous bypass, in three cases of middle cerebral artery aneurysms an extra
      intracranial bypass was also done combined with a resection of the aneurysm. The
      four patients suffering from an aneurysm of the basilar artery got an extra
      intracranial bypass too followed by an occlusion of the aneurysm with GD-Coils.
      RESULTS: There was no peri-operative mortality and no severe peri- or
      postoperative complication. The neurological symptoms of all patients were
      unchanged after the operation. An angiographic control showed a complete
      obliteration of the aneurysm and a free running bypass in all cases. CONCLUSION:
      Bypass surgery and combined bypass surgery and coil embolisation are effective
      methods in the treatment of giant cerebral aneurysms, which can not be treated by
      clipping alone.

PMID- 10955668
TI  - Factors influencing surgical complications of intra-axial brain tumours.
AB  - OBJECT: Extensive surgical resection remains nowadays the best treatment
      available for most intra-axial brain tumours. However, postoperative sequelae can
      outweigh the potential benefits of surgery. The goal of this study has been to
      review the results of this treatment in our Department in order to quantify
      morbidity and mortality and determine predictive risk factors for each patient.
      METHOD: We report a retrospective study of 200 patients submitted to a craniotomy
      for intra-axial brain tumours including gliomas and metastases. Postoperative
      major complications are analysed and related to different variables. An
      exhaustive review of the literature concerning the main controversial points
      about primary and metastatic brain tumours surgery is done. FINDINGS: The overall
      major complication rate was 27.5%, with neurological complications being the most
      frequently encountered. We did not find a statistically significant relation
      between them and the grade of eloquence of the tumoural area. Infratentorial
      tumour location, previous radiotherapy and reoperations were factors strongly
      related to the incidence of regional complications. Age over 60 and severe
      concomitant disease were risk factors for systemic complications. INTERPRETATION:
      The results from published series concerning surgical complications after
      craniotomies for brain tumours are not comparable because of the lack of
      homogeneity between them. The knowledge of the complications rate in each
      particular neurosurgical department turns out essentially to provide the patient
      with tailored information about risks before surgery.

PMID- 10955669
TI  - Transcranial transsphenoidal approach for tuberculum sellae meningiomas.
AB  - OBJECTIVE: A series of 21 patients with tuberculum sellae meningioma who received
      surgical treatment is reported. PATIENTS AND METHODS: All 9 females and 12 males
      (mean age 49 years) presented visual disturbances of varying degrees in either
      one or both eyes. Eighteen of the tumours were less than 3 cm in size, and 3 were
      larger. Tumour resection of uniform surgical technique was performed in all
      cases. Following a bicoronal scalp incision, bifrontal craniotomy combined with
      removal of the orbital rim bilaterally was performed. The frontal dura was opened
      bilaterally, and the most anterior portion of the superior sagittal sinus was
      transected. Bifrontal retraction and arachnoid dissection along the proximal
      olfactory tracts brought the tumour into view. Additional dissection of the
      interhemispheric fissure extended the operative field to the anterior
      communicating artery. The anterior skull base was drilled out to resect the basal
      part of the tumour. In all cases, the optic canal and sphenoid sinus, and
      additionally in some cases the ethmoid sinus were opened. The tumour uniformly
      extended inferomedially to the optic nerve, and direct visualization of this
      portion of the tumour was possible with our approach. The opened paranasal
      sinuses were reconstructed with adipose tissue harvested from the patient's
      abdomen and the pericranial flap. RESULTS: In all patients, total or almost total
      resection of the tumour was accomplished. Postoperatively, visual function was
      improved in 11 patients, was unchanged in 8, and worsened in 2. There were no
      operative deaths. Cerebrospinal fluid leakage was occurred in two patients but
      could be conservatively managed. In a mean 3-year follow-up, tumour recurrence
      was observed in only one patient who presented a malignant histology.
      CONCLUSIONS: We are confident that our surgical approach has great clinical value
      in surgical resection of tuberculum sellae meningioma. The good accessibility to
      a tumour extending inferomedially to the optic nerve should, in particular, be
      stressed.

PMID- 10955670
TI  - Changes in health related quality of life in patients with Parkinson's disease
      with and without posteroventral pallidotomy.
AB  - Traditional clinical outcome measures for the treatment of Parkinson's disease
      (PD) have focused on motor function and activities of daily living. However, in
      the past decade there has been a new emphasis on the use of health related
      quality of life (HRQOL) measures for translating how a patient's response to
      treatment is experienced by the patient. The purpose of this study was to
      describe patient reported HRQOL in subjects who underwent Posteroventral
      pallidotomy (PVP) for the treatment of PD compared with a similar group of
      subjects who did not undergo surgery (non-PVP). A consecutive series of patients
      who underwent PVP (n = 52) was compared prospectively with a similar group of
      patients, who received adjustments to medications without surgery (n = 45).
      Severity of disease and self reported HRQOL were evaluated at two time periods.
      Time 1 data were collected within one week prior to surgery for the PVP group or
      when subjects received medication adjustments for the non-PVP group. Time 2 data
      were collected 4 months later. Results showed that the severity of disease
      improved from Time 1 to Time 2 for both groups. HRQOL improved significantly for
      the PVP group (p = 0.001) but not for the non-PVP group (p > 0.29). Changes in
      HRQOL were most strongly related to the improvement in severity of disease in the
      "off" state. The results of this study suggest that PVP is associated with
      significant improvements in clinical and patient reported outcomes four months
      following surgery compared with a similar group of patients who did not undergo
      surgery. Additionally, the results suggest that the difference in perceived
      outcome between the groups is due in part to the improvement in the levodopa
      "off" periods which occurred for the PVP group but not for the non-PVP group.

PMID- 10955671
TI  - Neuro-Link, a computer-assisted database for head injury in intensive care.
AB  - Reliable information is vital for clinical trials, so we developed a database,
      for head trauma victims admitted to neuro-intensive care units (NICU). This
      database, first step in a sequential project, comprises 176 selected fields
      mainly focused on the early post-traumatic phase and has a user-friendly
      computerized interface. The software was tested for a trimester in 18 Italian
      neuro-intensive care units. The paper describes the main features of the
      database, the results of a three months' data collection test, its limitations
      and its potential improvements. A description of the database fields and a brief
      summary of the 282 patients included so far are also presented.

PMID- 10955672
TI  - Spinal subdural and epidural haematomas: diagnostic and therapeutic aspects in
      acute and subacute cases.
AB  - BACKGROUND: The diagnosis of spontaneous spinal haematomas mainly depends on
      magnetic resonance imaging. This study evaluates the MRI characteristics of
      spinal epidural and subdural haematomas. The results were correlated with medical
      history, coagulation abnormalities and therapeutic outcome to provide guidelines
      for early diagnosis and treatment of spinal epidural and subdural hematomas.
      SUMMARY OF BACKGROUND DATA: Imaging signs of epidural and subdural haematomas
      have been reported before, however without special attention to the differential
      diagnostic and therapeutic implications of haematoma localisation. METHOD: Seven
      patients (3 women, 4 men, age range 55-86 years) with acute progressive
      neurological deficits and without a history of severe trauma were studied. In all
      cases neurological examinations were performed after admission followed by MRI
      studies with T2 and T1 weighted images, before and after administration of
      contrast agent. Spinal angiography was performed twice to exclude a vascular
      malformation. All patients underwent open surgery. FINDINGS: Acute and subacute
      hematomas were detected once in the cervical spine, in five cases in the thoracic
      region and once in the lumbar region. The hematomas had an epidural location in
      three cases and a subdural in four. In the thoracic region subdural haemorrhage
      was much more common than epidural hematomas. Subdural blood collections were
      mainly found ventral to the spinal cord. Epidural haemorrhage was always located
      dorsal to the spinal cord. The evaluation of the haematoma localisation may be
      difficult occasionally, but delineation of the dura is frequently possible in
      good quality MRI. The clue to the diagnosis of ventrally located subdural
      haemorrhage is the absence of the "curtain sign", which is typical for epidural
      tumours. INTERPRETATION: Spontaneous spinal hematomas are frequently located in
      the thoracic spine. Subdural spinal haemorrhage is more frequent than epidural.
      Epidural haemorrhage is frequently located dorsal to the spinal cord because of
      the tight fixation of the dura to the vertebral bodies.

PMID- 10955673
TI  - Microsurgical treatment of spontaneous and non-spontaneous spinal epidural
      haematomas: neurological outcome in relation to aetiology.
AB  - BACKGROUND: This retrospective study evaluated the neurological outcome of 26
      patients with spontaneous and non-spontaneous spinal epidural haematoma (SEH) who
      underwent microsurgical clot removal. It was the objective of the present study
      to investigate whether the aetiology of the SEH has an influence on the
      neurological outcome. METHODS: The medical records and radiological
      investigations of 26 patients with SEH were re-examined, and the latency between
      symptom onset and operation, and the size of the haematoma were determined. Motor
      and sensory function had been evaluated before surgery and 90 days after
      discharge. FINDINGS: Fourteen patients with non-spontaneous SEH and 12 patients
      with spontaneous SEH were identified. After surgery, neurological deficits
      improved in 9 of the patients with spontaneous (75%) and in 13 of the patients
      with non-spontaneous SEH (93%). In cases of spontaneous SEH, the median latency
      between symptom onset and operation was longer (72 hrs vs 7 hrs) and the median
      extent of the haematoma was larger (3.5 vs 2 spinal segments), than in the non
      spontaneous cases. INTERPRETATION: Neurological outcome seems to be related to
      the aetiology of the SEH. Better outcome was observed in patients with surgically
      treated non-spontaneous SEH. Two explanations for this finding are worth
      considering. First, patients with non-spontaneous SEH usually are already under
      medical surveillance and can undergo medullary decompression more rapidly.
      Second, the compression of the spinal cord is possibly less severe in non
      spontaneous SEH because of their smaller size.

PMID- 10955674
TI  - Spinal arachnoiditis following subarachnoid haemorrhage: report of two cases and
      review of the literature.
AB  - Two patients with spinal arachnoiditis following subarachnoid haemorrhage are
      described. A complete spinal block was seen at the mid thoracic level with
      characteristics of spinal arachnoiditis. Only one patient had severe symptoms.
      Both patients were treated conservatively. Signs and symptoms diminished in time.
      A review of the literature is given and the aetiology is discussed.

PMID- 10955675
TI  - Radiation-induced brain calcification: paradoxical high signal intensity in T1
      weighted MR images.
AB  - BACKGROUND: Irradiation to the central nervous system (CNS) in childhood is known
      to induce cerebral calcification after a latent period. Calcification has been
      generally found to show nil or a reduction in signal intensity in magnetic
      resonance (MR) images. However, we have studied three patients with radiation
      induced brain calcification, who manifested increased signal intensity on T1
      weighted MR images. METHOD: Three girls had each been diagnosed as having a
      suprasellar germ cell tumour and were treated with conventional fractionated
      radiotherapy in their childhood. In one case, chemotherapy was given prior to the
      CNS irradiation. FINDINGS: All three patients survived their disease, and a
      follow-up CT scan revealed calcification in the brain, which has shown an
      increased signal intensity in the T1-weighted images of MR. INTERPRETATION:
      Cerebral calcification may be presented as a high signal intensity in the T1
      weighted MR images. This may be explained by a surface-relaxation effect by the
      calcium salt particle, precipitated in the brain due to radiation-induced
      mineralising microangiopathy.

PMID- 10955676
TI  - GDNF induces recovery of the nigrostriatal dopaminergic system in the rat brain
      following intracerebroventricular or intraparenchymal administration.
AB  - BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) has been shown to
      be a survival and neuroprotective factor for nigrostriatal dopaminergic neurons
      in vivo. The present study was designed to investigate the possible
      neuroprotective and restorative role by GDNF for dopaminergic neurons which were
      exposed to the neurotoxin 6-hydroxydopamine (6-OHDA). METHOD: We compared
      neurochemical, morphological and behavioural changes following striatal infusion
      of GDNF to those following intracerebroventricular (i.c.v.) infusion. FINDINGS:
      Apomorphine-induced rotation showed significant recovery after both types of
      infusion. Significant recovery of tyrosine hydroxylase (TH)-immunoreactive (IR)
      neurons and fibers were found in the substantia nigra and striatum following both
      striatum and i.c.v. infusion except for the number of TH-IR neurons in the i.c.v.
      infusion group. INTERPRETATION: These results suggest that GDNF induces recovery
      of the nigrostriatal dopaminergic system, and this indicates a potential
      usefulness of GDNF for the treatment of Parkinson's disease.

PMID- 10955677
TI  - The effects of hypertonic saline on spinal cord blood flow following compression
      injury.
AB  - 7.5% hypertonic saline was administered following spinal cord injury to test its
      effect on spinal cord blood flow. Four different groups of rats underwent 10
      minutes of spinal cord compression (45 g) at the C3 to C5 levels. A fifth group
      was not injured, but received hypertonic saline (5 ml/kg) at 5, 15 and 60 minutes
      following injury. Somatosensory evoked potentials and spinal cord blood flow were
      measured prior to and for 4 hours following the injury. The administration of
      hypertonic saline caused a significant increase in flow when administered 5
      minutes following injury. Topical nitroprusside administration did not cause any
      increase in spinal cord blood flow during this time period. Hypertonic saline
      administration at the later time periods did not increase spinal cord blood flow.
      The group of animals which were not injured, but received hypertonic saline also
      showed no significant change in flow. The somatosensory evoked response of the
      treated animals was maintained for 4 hours after the injury where as the
      untreated animals began to lose their evoked responses 3 hours after injury.

PMID- 10955679
TI  - Intracerebral ossification.

PMID- 10955678
TI  - Cocaine-related acute subdural hematoma: an emergent cause of cerebrovascular
      accident.
AB  - A case of "spontaneous" acute subdural hematoma caused by cocaine abuse is
      described. As an isolated cerebrovascular event, related to cocaine abuse, this
      is the first report in the literature. It also represents a new differential
      diagnosis for nontraumatic acute subdural haematomas. The putative
      pathophysiology of the lesion is discussed.

PMID- 10955680
TI  - Early bifurcation of the left A1 segment giving rise to both A2 segments and a
      hypoplastic right A1 segment.

PMID- 10955681
TI  - Staged surgical occlusion of a cerebral arteriovenous fistula.

PMID- 10955682
TI  - Cerebral meningioangiomatosis: MRI and MRS findings.

PMID- 10955683
TI  - Pigmented squamous cell carcinoma of the skin: morphologic and
      immunohistochemical study of five cases.
AB  - Invasive pigmented squamous cell carcinoma (PSCC) of the skin is reportedly rare.
      Herein, we evaluate an additional five cases and compare their relative frequency
      with non-pigmented squamous cell carcinoma (SCC). Of 46,791 archived cases of
      SCC, a total of five cases of PSCC were discovered for a relative frequency of
      approximately 0.01%. Grossly, each tumor presented as a rapidly growing crusted
      papule on actinic damaged skin of the face. Microscopically, all were composed of
      a mixture of keratininized squamous cells and melanin-producing dendritic
      melanocytes. The squamous cells stained for epithelial membrane antigen, and both
      low and high molecular keratins. The melanocytes stained for S-100 and HMB-45. A
      matched series of 31 SCCs were subjected to an identical immunohistochemical
      battery of stains to determine if a histologically subtle and unsuspected number
      of intratumoral melanocytes existed in SCC. Each of the cases failed to show
      intratumoral melanocytes. The differential diagnosis and possible histogenesis of
      PSCC is discussed and the importance of extensive pathologic examination to
      prevent misdiagnosis is emphasized. Despite the histologic dissimilarity, the
      long-term prognosis of the reported cases was similar to conventional SCC.

PMID- 10955684
TI  - Pagetoid dyskeratosis of the prepuce. An incidental histologic finding resembling
      extramammary Paget's disease.
AB  - BACKGROUND: Pale cells resembling those of paget's disease have been seen as an
      incidental finding within the epidermis in a variety of benign papules most
      commonly located in intertriginous areas. This lesion, called pagetoid
      dyskeratosis, is considered a reactive process in which a small part of the
      normal population of keratinocytes is induced to proliferate. Among the inductors
      friction is suspected. As far as we know, these cells have not been reported in
      the penis. METHODS: Here we describe the location of the lesion in the foreskin
      and the incidence of this lesion in a group of 281 unselected patients surgically
      treated for phimosis. In selected cases histochemical staining and
      immunohistochemical studies were performed. RESULTS: Pagetoid dyskeratosis was
      found in 105 cases (37.4%) but only in 5 cases (1.8%) the lesion was conspicuous.
      The cells of pagetoid dyskeratosis show an immunohistochemical profile different
      from the surrounding keratinocytes characterized by premature keratinization.
      Pagetoid dyskeratosis cells must be distinguished from the artefactual clear
      cells of the epidermis, from reactive melanocytes, and from pale-cell acanthosis.
      In cases in which pagetoid dyskeratosis shows a florid expression there is a
      hazard of overdiagnosis to the patient. The main differential diagnosis includes
      extramammary Paget's disease, pagetoid squamous cell carcinoma in situ,
      epidermotropic metastasis, superficial spreading malignant melanoma, clear cell
      papulosis, and penile koilocytoses. CONCLUSIONS: The pathologist should be
      familiar with the histologic features of pagetoid dyskeratosis in the foreskin in
      order to avoid misdiagnosis and unnecessary treatment. Routine histologic study
      is usually sufficient to identify the lesion.

PMID- 10955685
TI  - Co-expression of CD56 and CD30 in lymphomas with primary presentation in the
      skin: clinicopathologic, immunohistochemical and molecular analyses of seven
      cases.
AB  - BACKGROUND: Natural killer and natural killer-like T-cell lymphomas presenting in
      the skin usually demonstrate aggressive behavior, an angiocentric distribution
      and a characteristic immunophenotype. In contrast, primary cutaneous CD30+
      lymphoproliferative disorders form a heterogeneous spectrum including anaplastic
      large cell lymphomas, the majority of which display a good prognosis. Lymphomas
      with co-expression of CD56 and CD30 are extremely rare and the significance of
      this co-expression is unknown. METHODS: Seven retrospectively identified cases of
      lymphomas with co-expression of CD56 and CD30 presenting in the skin comprise
      this study. Immunohistochemistry, in situ hybridization for Epstein-Barr virus
      and T-cell receptor gene rearrangement studies were performed on paraffin
      sections. RESULTS: This subset of cutaneous lymphomas showed a variable clinical
      course that ranged from resolution without treatment, treatment-failure and
      recurrence, to death from disease. Histologic, immunophenotypic and molecular
      studies were of limited utility in predicting prognosis. CONCLUSIONS: Cutaneous
      lymphomas co-expressing CD56 and CD30 share many clinicopathologic features with
      natural killer and natural killer-like T-cell lymphomas or anaplastic large cell
      lymphomas, two entities with widely disparate clinical behavior. It is important
      to recognize that these lymphomas may behave more aggressively than primary
      cutaneous anaplastic large cell lymphomas do. Longer follow-up and further
      investigations on larger numbers of cases are necessary to fully characterize
      this rare subset of cutaneous lymphomas.

PMID- 10955686
TI  - Apoptosis and expression of Bax/Bcl-2 proteins in pyogenic granuloma: a
      comparative study with granulation tissue and capillary hemangioma.
AB  - BACKGROUND: Pyogenic granuloma (PG) has been regarded as a florid expression of
      granulation tissue (GT) proliferation and shows distinct biological behavior
      compared to conventional GT. PG has not been examined from a standpoint of
      apoptosis. METHODS: PG (15 cases), GT (14 cases) and capillary hemangioma (CH, 8
      cases) were compared using in situ 3'-tailing reaction (ISTR), a histochemical
      method for identifying apoptotic cells, and immunohistochemistry for Ki-67, Bcl-2
      and Bax proteins, in order to clarify and involvement of apoptosis in the
      difference of biological characteristics between PG and GT. RESULTS: PG showed
      significantly lower ISTR-labeling indices than GT and CH and more frequent Bcl
      2/Bax expression than GT, whereas Ki-67-labeling indices were variable from case
      to case and did not show any significant differences among any groups.
      CONCLUSIONS: It is consequently suggested that the low apoptotic rate in PG is
      closely related to its characteristic rapid growth and is regulated by Bcl-2
      family proteins.

PMID- 10955687
TI  - The histologic value of adnexal (eccrine gland and follicle) infiltration in
      mycosis fungoides.
AB  - BACKGROUND: To verify the incidence and the possible diagnostic use of detecting
      adnexotropism in mycosis fungoides (MF). METHODS: We reviewed the frequency and
      the intensity of the eccrine and follicular infiltration in 104 biopsy specimens
      from indisputable cases of MF and in a control group of 20 biopsy specimens of
      spongiotic dermatitis. Syringohyperplasia and follicular mucinosis were also
      evaluated. RESULTS: A prominent eccrine infiltration was noted in 32 of 104
      specimens (30%). Marked acrosyringial and ductal eccrine hyperplasia was present
      in 5 specimens (5%). In 13 of the 32 specimens with prominent eccrine
      infiltration (40%), epidermotropism was slight or less evident than
      syringotropism. Follicular structures were visible in 59 specimens and
      significantly infiltrated in 57%. Follicular mucinosis was found in 5 (8.4%). In
      the control group of spongiotic dermatitis, a significant eccrine and follicular
      infiltration was found only in case (5%). CONCLUSIONS: Adnexal (eccrine gland and
      follicle) infiltration may be a useful diagnostic tool in MF, particularly in
      those in which epidermotropism is slight.

PMID- 10955688
TI  - Livedoid vasculopathy in a patient with factor V mutation (Leiden).
AB  - BACKGROUND: Frequently, no underlying disease can be detected in patients with
      livedoid vasculopathy. For these forms, an unknown vaso-occlusive or thrombogenic
      process has been accused to play a role. Thus, a patient with livedoid
      vasculopathy was examined for different parameters which can be involved in
      coagulopathies. METHODS: Laboratory studies for different autoantigen reactive
      immunoglobulins, cryoglobulins, and circulating immune complexes were carried
      out. Besides dermatopathologic examination, a biopsy specimen was analyzed by
      direct immunofluorescence for immunoglobulin (Ig) and complement deposits.
      Furthermore, hemostaseological function tests including activated protein C (APC)
      resistance were undertaken. RESULTS: Positive only at very low titres were
      antinuclear antibodies and c-ANCA, all other parameters were within normal ranges
      or negative. Direct immunofluorescence revealed IgM, C3 and fibrogen deposits.
      Hemostaseological function tests demonstrated a pathologic activated protein c
      resistance and PCR analysis a heterozygous defect of the factor V (Leiden).
      CONCLUSIONS: The diagnosis of livedoid vasculopathy associated with factor V
      mutation (Leiden) was made. Since the underlying cause for livedoid vasculopathy
      often remains unknown, we suggest that hemostaseological function tests including
      APC resistance and factor V gene mutation analysis should be carried out. Further
      studies have to follow in order to elucidate the role of mutant factor V in
      livedoid vasculopathy and in cutaneous ulcerations.

PMID- 10955689
TI  - A case of intravascular large B-cell lymphoma mimicking erythema nodosum: the
      importance of multiple skin biopsies.
AB  - BACKGROUND: Intravascular lymphoma is a rare disease characterized by the
      proliferation of neoplastic monuclear cells within the lumens of small blood
      vessels. The neoplastic cells are usually of B-cell origin, and rarely of T-cell
      or histiocytic origin. Although this clinicopathological entity of lymphoma has
      not been listed in general pathological classifications such as REAL
      classification or the Working Formulation, it is recently in the WHO
      classification scheme, which is essentially an updated REAL scheme, and the EORTC
      classification scheme. METHODS: In this report, a 62-year-old woman with
      intravascular large B-cell lymphoma was observed by clinical, histopathological,
      immunohistochemical and molecular methods. RESULTS: A 62-year-old woman presented
      with large erythematous macules on the bilateral thighs and lower legs. The
      lesions were accompanied with hard, tender, intradermal or subcutaneous nodules
      mimicking erythema nodosum. Histopathological examination in the first biopsy
      revealed non-specific panniculitis compatible with erythema nodosum. The second
      biopsy revealed emboli of atypical lymphocytes within many of the dilated and
      proliferated vessels in the deep dermis and subcutaneous tissue. These cells were
      positive for L-26 and kappa light chain, and negative for lambda light chain,
      factor VIII-related antigen, CD30, CD34, CD68 and UCHL-1. These findings
      confirmed the diagnosis of intravascular large B-cell lymphoma. A laboratory
      examination showed a high level of LDH and abnormal cells in the bone marrow. An
      MRI of the brain and computed tomographic (CT) scans of the chest and abdomen
      revealed no evidence of malignancy. Before the treatment, the size of the nodules
      decreased spontaneously by about 50% in one month and significantly in two
      months. Although combination chemotherapy, which consisted of CHOP, brought her
      partial remission, she experienced neurological symptoms 6 months after the
      initial treatment and died of brain metastasis 9 months after the treatment.
      CONCLUSIONS: This is a unique case for two following reasons: 1) the first biopsy
      revealed non-specific findings compatible with erythema nodosum; and 2) before
      the treatment, the nodules regressed spontaneously. Dermatologists should take
      multiple skin biopsies for EN lesions with the non-specific histopathological
      findings not to refute the existence of this disease.

PMID- 10955690
TI  - Unusual second malignancies following radiation therapy: subcutaneous pleomorphic
      rhabdomyosarcoma and cutaneous melanoma. Two case reports.
AB  - BACKGROUND: Among nonepithelial second neoplasms which are known to be induced by
      irradiation, rhabdomyosarcomas are extremely rare, and melanomas are infrequent.
      We report a high-grade sarcoma with rhabdomyoblastic differentiation, which
      appeared 30 years after megavoltage irradiation for an endometrial
      adenocarcinoma, and a malignant melanoma which arose after 6 years in the
      irradiation field of a fibrosarcoma. METHODS: Histology and immunohistochemistry
      were performed in both cases. In the first case, electron microscopy was also
      performed. In the second, the previous tumor was re-evaluated. RESULTS: The first
      case showed histological, immunohistochemical and ultrastructural features of a
      rhabdomyosarcoma. In the second case, a lentigoid malignant melanoma was
      histologically and immunohistochemically demonstrated, whereas the previously
      resected tumor was a fibrosarcoma negative to melanoma markers. CONCLUSIONS: Rare
      cases of rhabdomyosarcomas and melanomas are induced by irradiation, although in
      some cases other factors (i.e., genetic risk, chemotherapy) may have a prominent
      etiopathogenetic role in their development. A close follow-up and a careful
      examination of the irradiated area should facilitate an early diagnosis of these
      aggressive postradiation second neoplasms.

PMID- 10955691
TI  - Nodular hidradenocarcinoma with prominent squamous differentiation: case report
      and immunohistochemical study.
AB  - We report the case of a 24-year-old woman with nodular hidradenocarcinoma on the
      scalp. While histopathology of the tumor showed a circumscribed, lobulated
      intradermal mass with prominent squamous differentiation, the immunohistochemical
      study with antibodies to cytokeratins, CAM 5.2 and 19, epithelial membrane
      antigen, carcinoembryonic antigen, S-100 protein and p53 all demonstrated
      positivity. These findings confirmed that the tumor was of eccrine sweat gland
      origin and it was thought to be a nodular hidradenocarcinoma differentiating
      toward the eccrine duct and/or secretory portions. She was treated with a wide
      local excision and no recurrence was observed 18 months after excision.

PMID- 10955692
TI  - Nosing out the future asthmatic?

PMID- 10955693
TI  - The development of the immune system during pregnancy and early life.

PMID- 10955694
TI  - Contact allergy to corticosteroids.

PMID- 10955695
TI  - Association of asthma symptoms and severity with indoor bioaerosols.
AB  - BACKGROUND: In this study, repeated measurements were made of levels of mold
      spores, bacteria, and dust-mite allergens over a 7-month period in the homes of
      asthmatics, and relationships with measures of asthma severity were evaluated.
      METHODS: A sample of 57 asthmatic individuals, living in 44 homes in East Moline,
      Illinois, and nearby communities, participated in a panel study. The homes were
      visited up to nine times during the study to collect air and dust samples. Asthma
      severity indicators were derived from questionnaire data and from the daily
      health records from the panel study. Associations between indoor levels of mold
      spores, bacteria, and dust-mite allergens were tested with several asthma
      severity indicators. RESULTS: There was evidence of associations between all
      asthma severity measures and levels of total and gram-negative bacteria, but mold
      spore abundance was associated only with emergency room (ER) visits for asthma.
      No significant associations were found with house-dust-mite allergen and any of
      the asthma severity indicators, but the levels of dust-mite allergen were low,
      with median concentrations of 0.18 microg/g dust Der f 1 and 0.19 microg/g dust
      Der p 1. CONCLUSIONS: Some evidence was found for associations of increased
      concentrations of gram-negative bacteria and mold spores with asthma severity,
      particularly with ER visits. No association was found between house-dust-mite
      allergen and asthma severity indicators; however, the mite-allergen levels in the
      study homes were generally well below the proposed threshold level of 2 microg/g
      dust.

PMID- 10955696
TI  - PCR-based cloning, isolation, and IgE-binding properties of recombinant latex
      profilin (rHev b 8).
AB  - BACKGROUND: Profilin (Hev b 8) in natural rubber latex (NRL) has been assumed to
      be an important allergen. Since latex profilin has a molecular mass similar to
      two other latex allergens (Hev b 1 and Hev b 6.03) in the 14-kDa range, it is
      difficult to obtain sufficient amounts of purified native profilin for
      investigations and diagnostics. The present study aimed to produce recombinant
      latex profilin (rHev b 8) and study its IgE-binding reactivity. METHODS: A
      profilin-specific cDNA encoding the latex profilin from Hevea brasiliensis leaves
      was synthesized and subcloned, and the rHev b 8 was overexpressed in fusion with
      the maltose-binding protein (MBP) in E. coli. The IgE-binding reactivity of rHev
      b 8 was studied by immunoblotting, immunoblot inhibition experiments, and the
      Pharmacia CAP method, with 25 sera from health-care workers with latex allergy
      and 17 sera from latex-sensitive spina bifida patients. RESULTS: rHev b 8 was
      found to have 131 amino acids and a sequence identity of 75% with birch profilin
      (Bet v 2). Analysis by the CAP system revealed the presence of rHev b 8-specific
      IgE antibodies in two out of 17 sera from spina bifida patients and in five out
      of 25 sera (20%) from health-care workers. Two subjects of the latter group with
      rHev b 8-specific IgE showed negative results in the skin prick tests with tree
      pollen extracts and had no IgE to rBet v 2, indicating the presence of IgE
      binding epitopes on the Hev b 8-molecule which do not cross-react with birch
      profilin. Immunoblot inhibition assays using MBP-rHev b 8 as inhibitor confirmed
      the presence of latex profilin in the NRL extract. IgE binding to the native
      latex profilin could be completely inhibited by the MBP-rHev b 8. CONCLUSIONS:
      Latex profilin represents a minor allergen in NRL and may have IgE-binding
      epitopes different from Bet v 2.

PMID- 10955697
TI  - Clinical and pathologic methods to assess the long-term safety of nasal
      corticosteroids. French Triamcinolone Acetonide Study Group.
AB  - BACKGROUND: The main objective of this long-term prospective local safety study
      was to evaluate endoscopic and histologic changes in nasal epithelium after 6
      month treatment with triamcinolone acetonide (TAA). We describe here a method to
      measure quantitatively epithelium thickness. Results were compared with those
      seen with the use of cetirizine (an antihistamine) and another oral intranasal
      corticosteroid, beclomethasone dipropionate (BDP). METHODS: Patients were
      examined by an ENT specialist who first performed an endoscopic evaluation of the
      nasal cavities, assessing any morphologic abnormalities and the aspect of the
      mucosa. Biopsies were taken from the inferior turbinate before and after 24 weeks
      of treatment. Biopsies were immediately fixed in cold acetone (-20 degrees C) and
      embedded in glycolmethacrylate; sections of 2 microm were cut on an
      ultramicrotome. Morphometric evaluations were done in a blinded fashion by
      computerized image analysis to measure an epithelial area over a minimum length
      of 50 microm. The thickness was ascertained by the ratio of area to length.
      RESULTS: 1) For all three treatment groups, the nasal epithelium thickness
      decreased slightly from pretreatment to the end of treatment. 2) No statistically
      significant differences between the three treatment groups were found in
      epithelium thickness. 3) Macroscopically, nasal tissues in all treated groups
      were normal. CONCLUSIONS: These results clearly indicate that long-term treatment
      with TAA has no atrophic effect on nasal mucosa.

PMID- 10955698
TI  - Interleukin-4-independent production of Th2 cytokines by nasal lymphocytes and
      nasal eosinophilia in murine allergic rhinitis.
AB  - BACKGROUND: Interleukin (IL)-4 is believed to play an important role in the
      atopic pathogenesis. However, the precise role of IL-4 in the in vivo initiation
      of allergic rhinitis is not fully understood. We have recently found that BALB/c
      mice sensitized intranasally with Schistosoma mansoni egg antigen (SEA) mount a
      Th2 response that initiates allergic rhinitis. Thus, we sought to determine the
      role of IL-4 in the initiation of allergic rhinitis in vivo with this model.
      METHODS: IL-4 gene-deficient (IL-4 -/-) BALB/c and wild-type (IL-4 +/+) control
      mice were sensitized by intranasal SEA administration, and their immunologic
      responses were examined both in vivo and in vitro. RESULTS: IL-4 +/+ mice
      sensitized with SEA displayed significantly higher titers of SEA-specific IgG1
      and IgE antibodies than IL-4-/- mice, while the latter produced significantly
      more SEA-specific IgG2a. Antigen-stimulated nasal lymphocytes from SEA-sensitized
      IL-4 -/- and IL-4 +/+ mice produced similar amounts of IL-5 and IL-10, but
      neither produced IFN-gamma. Furthermore, the severity of nasal eosinophilia was
      similar in both groups. CONCLUSIONS: These results indicate that although IL-4 is
      necessary for the production of Th2-associated antibodies--in particular, IgE--it
      is not required for either the production of the Th2-associated cytokines IL-5
      and IL-10, or the induction of nasal eosinophilia.

PMID- 10955699
TI  - Prenatal immune priming with helminth infections: parasite-specific cellular
      reactivity and Th1 and Th2 cytokine responses in neonates.
AB  - The present investigation aimed to determine to what extent maternal helminth
      infection primes parasite-specific cellular responsiveness in neonates. Umbilical
      cord mononuclear blood cells (UCBC) and peripheral blood mononuclear cells (PBMC)
      from mothers proliferated in response to mitogenic stimulation with concanavalin
      A, as well as to bacterial Streptococcus pyogenes-derived (streptolysin O) and
      helminth-specific antigens of Necator americanus and Onchocerca volvulus.
      Cellular responses to Echinococcus multilocularis (Em) and Oesophagostomum
      bifurcum (Oes), helminth parasites not endemic in the study area, were absent
      (for Em) or very low (for Oes due to antigenic cross-reactivity). Cellular
      responsiveness to mitogen and antigens was higher in mothers than in their
      neonates. Several Th1-type (IL-2, IL-12, and IFN-gamma) and Th2-type (IL-5 and IL
      10) cytokines were produced by UCBC from neonates and PBMC from mothers. Low
      levels of IFN-gamma were elicited by UCBC in response to helminth and bacterial
      antigens, while secretion of IL-2 was pronounced and similarly high in neonates
      and their mothers. Amounts of IL-5 produced by UCBC in response to bacterial SL-O
      and mitogenic stimulation (PHA) were low, but equivalent levels of IL-5 were
      induced by intestinal helminth and filaria-derived antigens in neonates and
      mothers. A pronounced production of IL-10 and IL-12 by UCBC was observed-
      spontaneous IL-10 and IL-12 secretion by UCBC was higher in neonates than by PBMC
      from mothers. Net amounts of IL-10 elicited by helminth antigens were similar,
      while net IL-12 in response to mitogen, and bacterial and helminth antigens was
      significantly higher in mothers than their offspring. Our results indicate that
      human maternal helminth infection does sensitize in utero for parasite-specific
      cellular responsiveness in offspring, and also activates specific production of
      several cytokines, and such children do not present a dominant expression of
      immunity of either Th1 or Th2.

PMID- 10955700
TI  - Low-dose inhaled budesonide once or twice daily for 27 months in children with
      mild asthma.
AB  - This study is an extended follow-up for 24 months of a 12-week trial to study the
      long-term clinical efficacy of low-dose inhaled budesonide (BUD) once or twice
      daily in children with mild asthma. A total of 122 children (mean age 9.7 years,
      girls/boys; 42/80) with mild asthma (FEV1 103.7% of predicted, reversibility in
      FEV1 3.5%, and fall in FEV1 after exercise 12.2%), not previously treated with
      inhaled steroids, were included in a double-blind, randomized, parallel-group
      study. The children were treated with inhaled BUD 100 or 200 microg administered
      via Turbuhaler once daily in the morning, 100 microg twice daily, or placebo for
      27 months. Exercise and methacholine challenges were performed at 3-month
      intervals the first year and at 6-month intervals the second year, in a total of
      seven visits. A significant dose-response effect favoring BUD 200 microg daily
      (vs 100 microg daily) was found when comparing changes in FEV1, FEF25%, and
      FEV50%; the fall in FEV1 after an exercise test; and the effect on blood
      eosinophils. Bronchial hyperreactivity to methacholine decreased significantly on
      three visits in patients treated with BUD 200 microg daily compared to placebo.
      Growth rate was not significantly affected except in children aged 7-11 years at
      baseline after 12 months of treatment. In conclusion, 100 or 200 microg daily of
      inhaled BUD for 27 months is safe and effective in protecting against exercise
      induced asthma and achieving nearly normal lung function. Baseline lung function
      was not significantly affected in this group of children with mild asthma.

PMID- 10955701
TI  - IL-12 regulates bone marrow eosinophilia and airway eotaxin levels induced by
      airway allergen exposure.
AB  - BACKGROUND: Airway allergen exposure causes local eosinophilic cell infiltration.
      This cellular inflammatory response is likely to involve the release of
      eosinophils from peripheral storage pools, and possibly also regeneration of
      eosinophils in the bone marrow. IL-12 is an inhibitory cytokine in allergic
      inflammation, shown to reduce eosinophilic cell infiltration. The aim of the
      present study was to determine whether airway allergen exposure increases bone
      marrow eosinophil production, and, if so, whether IL-12 modulates this effect.
      METHODS: Ovalbumin-sensitized C57BL/6 mice and IL-12 knockout (KO) mice were
      exposed to allergen via the airway route, and the inflammatory cell response was
      evaluated in bronchoalveolar lavage fluid, blood, and bone marrow. RESULTS:
      Allergen instillation intranasally produced a dose-dependent inflammatory
      response in the lower airways of sensitized mice. This inflammatory response was
      dominated by eosinophils, but there were also increases of both lymphocytes and
      neutrophils. Sensitization and airway allergen exposure also increased the IL-5
      dependent growth of bone marrow cells in vitro. The enhanced bone marrow
      responsiveness in vitro was paralleled by an increased number of bone marrow
      eosinophils in vivo. After sensitization and repeated allergen exposure, IL-12 KO
      mice showed higher eosinophil levels in both BAL and bone marrow than parallel
      wild-type control mice. Furthermore, BAL-eotaxin levels were increased in IL-12
      KO mice as opposed to parallel wild-type controls after allergen exposure.
      CONCLUSIONS: Airway allergen exposure induced systemic immunologic responses,
      including increased eosinophil numbers in both airways and bone marrow, and also
      enhanced IL-5 responsiveness in bone marrow cells. IL-12 may regulate airway
      eosinophilia at both the level of eosinophilopoiesis and the level of local
      recruitment of eosinophils into the airways.

PMID- 10955702
TI  - The effect of platelet-activating factor (PAF) on nasal airway resistance in
      healthy subjects is not mediated by nitric oxide.
AB  - BACKGROUND: The nose is an important source of nitric oxide (NO) in man, but the
      relevance of NO production to the response to inflammatory mediators is not
      clear. METHODS: In this study, we evaluated the effect of NO inhibition on nasal
      airway resistance (NAR) at baseline, after an acute challenge with platelet
      activating factor (PAF), a potent proinflammatory factor, and after an acute
      challenge with bradykinin (BK), both of which are mediators of allergic rhinitis
      in man. Eight healthy subjects were enrolled in the study. Nasal NO production
      was measured by the chemiluminescence method, and NAR was measured by active
      anterior rhinomanometry. RESULTS: Basal nasal NO concentration was 500.6+/-115.6
      ppb; it significantly decreased after topical administration of the NO-synthase
      inhibitor L-NAME, and the NO-synthase substrate L-arginine caused a recovery in
      NO production. The administration of L-NAME did not cause any change in basal
      NAR. In a double-blind fashion, we performed nasal challenge with PAF and BK
      after topical pretreatment with either placebo or L-NAME. After placebo
      pretreatment, both PAF and BK caused a significant increase in NAR (respectively,
      from 0.29+/-0.11 Pa s cm(-3) to 0.75+/-0.21 Pa s cm(-3), and from 0.36+/-0.18 Pa
      s cm(-3) to 0.71+/-0.25 Pa s cm(-3); P<0.001, n=8). Pretreatment with L-NAME did
      not prevent the PAF-induced increase in NAR (from 0.31+/-0.10 Pa s cm(-3) to
      0.71+/-0.27 Pa s cm(-3)), whereas it prevented the BK-induced increase in NAR
      (from 0.33+/-0.15 Pa s cm(-3) to 0.43+/-0.16 Pa s cm(-3)). CONCLUSIONS: Topical
      administration of the NO-synthase inhibitor L-NAME at doses sufficient to
      decrease NO nasal production does not prevent the PAF-induced increase in NAR,
      indicating that NO generation in vivo is not involved in the nasal response to
      PAF.

PMID- 10955703
TI  - The association between atopy and asthma in a semirural area of Tanzania (East
      Africa).
AB  - BACKGROUND: Atopy is consistently associated with asthma, except in a study in
      Africa. We assessed the association between atopy and asthma in women from a
      semirural area of Tanzania (East Africa). METHODS: All pregnant women delivering
      at the district hospital during a 1-year period were recruited (n = 658, 60.6% of
      those selected). Asthma was investigated by a standard questionnaire and atopy by
      specific IgE (immunoglobulin E) antibodies to Dermatophagoides pteronyssinus (Der
      p 1) and cockroach. RESULTS: The prevalence of wheezing chest was 10.7%; of
      asthma, 3.5%. Levels of specific IgE of >0.35 kU/l (73%) and high levels of total
      IgE (62% higher than 1000 kU/l) were highly prevalent. Specific IgE antibody
      levels in sera were not associated with asthma (3.8% of women with negative
      specific IgE to any antigen had asthma in comparison to 4.0% of women with
      positive specific IgE; odds ratio [OR] = 1.06, 0.35-3.22). Total IgE was not
      different between women with asthma and women without asthma (P=0.36).
      CONCLUSIONS: In tropical regions, the association between allergy and asthma is
      complex, and specific IgE reactivity to environmental allergens may not be
      related to asthma.

PMID- 10955704
TI  - The prevalence of skin-test-positive allergic rhinitis in Danish adults: two
      cross-sectional surveys 8 years apart. The Copenhagen Allergy Study.
AB  - BACKGROUND: It is disputed whether increases in self-reported respiratory allergy
      represent a true increase or merely increased recognition. We aimed to
      investigate whether the prevalence of skin-prick-test (SPT)-positive allergic
      rhinitis had increased in an adult general population in Copenhagen, Denmark.
      METHODS: Two cross-sectional surveys were carried out in 1990 and 1998. A
      screening questionnaire on respiratory symptoms in random samples of 15-41-year
      olds preceded both surveys. Among the responders, random samples were invited to
      a health examination including SPT. Totals of 312 (participation rate 74.6%) and
      482 (participation rate 53.4%) subjects were examined in 1990 and 1998,
      respectively. Diagnoses of SPT-positive allergic rhinitis were based on a history
      of nasal symptoms on exposure to allergens and SPT positivity to allergens.
      RESULTS: The prevalence of a diagnosis of SPT-positive allergic rhinitis
      increased from 12.9% to 22.5% (adjusted odds ratio 1.94, 95% CI 1.30-2.90),
      whereas the prevalence of a positive SPT (allergen histamine wheal ratio > or =
      0.5) to one or more of 10 allergens increased from 27.7% to 33.9% (adjusted odds
      ratio 1.47, 95% CI 1.05-2.05). CONCLUSIONS: The prevalence of SPT-positive
      allergic rhinitis has increased significantly. Our findings indicate that a true
      increase in respiratory allergy has occurred.

PMID- 10955706
TI  - Unsuccessful rapid intravenous desensitization to rifampicin.

PMID- 10955705
TI  - Eosinophil-derived proteins in nasal lavage fluid of neonates of allergic parents
      and the development of respiratory symptoms during the first 6 months of life.
      Collaborative SPACE team. Study on the Prevention of Allergy in Children in
      Europe.
AB  - BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis
      for a proportion of children at risk of developing recurrent wheezing. Early
      preventive measures and/or anti-inflammatory treatment may be guided by the
      identification of such children. METHODS: We studied upper-airways inflammation
      by nasal lavage in a cohort of 397 infants within the first 4 weeks of life. They
      participated in an international multicenter study on the prevention of allergy
      in Europe (SPACE-Biomed II Program). A volume of 2 ml of prewarmed 0.9% saline
      was instilled into each nasal cavity and immediately re-collected by a suction
      device. The average recovery was 502 microl (SD: 311 microl). The concentrations
      of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were
      determined by RIA analysis. RESULTS: ECP was detectable (>2 microg/l) in 47% of
      samples (173/365) and EPX (>3 microg/l) in 54.7% (197/360). Children with a
      doctor's diagnosis of a wheezy bronchitis within the first 6 months of life (n =
      40) had significantly higher ECP and EPX concentrations in the nasal lavage at 4
      weeks of age (median ECP: 14 microg/l; 5-95th percentile: 0-122.4 microg/l) than
      children without such diagnosis (median ECP: 0 microg/l; 5-95th percentile: 0
      86.6 microg/l; P<0.05). Corresponding figures for EPX were 12.14 microg/l (0
      148.98 microg/l) vs 7.5 microg/l (0-81.46 microg/l; P<0.05). No associations
      between nasal ECP/EPX and the development of food allergy or eczema were
      observed. CONCLUSIONS: Increased nasal ECP and EPX in the first 4 weeks of life
      are associated with wheezing in 6-month-old infants at increased risk of atopic
      disease. We suggest that this might be related to a general tendency for a Th2
      cytokine pattern in these young infants and subsequent trafficking of eosinophils
      into the nasal mucosa, or it might be a consequence of intrauterine allergen
      exposure.

PMID- 10955707
TI  - Occupational asthma caused by aluminum.

PMID- 10955708
TI  - Air purification and indoor biologic pollutants.

PMID- 10955709
TI  - Swimming-pool pneumonitis.

PMID- 10955710
TI  - Nasal function of skiers in cold weather.

PMID- 10955711
TI  - IgE antibody to parasite induced in mice.

PMID- 10955712
TI  - Interleukins in Churg-Strauss syndrome.

PMID- 10955713
TI  - Selective hypersensitivity to piperacillin.

PMID- 10955714
TI  - Systemic anticholinergic side-effects.

PMID- 10955715
TI  - Ethoxyresorufin-O-deethylase (EROD) activity in fish as a biomarker of chemical
      exposure.
AB  - This review compiles and evaluates existing scientific information on the use,
      limitations, and procedural considerations for EROD activity (a catalytic
      measurement of cytochrome P4501A induction) as a biomarker in fish. A multitude
      of chemicals induce EROD activity in a variety of fish species, the most potent
      inducers being structural analogs of 2,3,7,8-tetracholordibenzo-p-dioxin.
      Although certain chemicals may inhibit EROD induction/activity, this interference
      is generally not a drawback to the use of EROD induction as a biomarker. The
      various methods of EROD analysis currently in use yield comparable results,
      particularly when data are expressed as relative rates of EROD activity. EROD
      induction in fish is well characterized, the most important modifying factors
      being fish species, reproductive status and age, all of which can be controlled
      through proper study design. Good candidate species for biomonitoring should have
      a wide range between basal and induced EROD activity (e.g., common carp, channel
      catfish, and mummichog). EROD activity has proven value as a biomarker in a
      number of field investigations of bleached kraft mill and industrial effluents,
      contaminated sediments, and chemical spills. Research on mechanisms of CYP1A
      induced toxicity suggests that EROD activity may not only indicate chemical
      exposure, but also may also precede effects at various levels of biological
      organization. A current research need is the development of chemical exposure
      response relationships for EROD activity in fish. In addition, routine reporting
      in the literature of EROD activity in standard positive and negative control
      material will enhance confidence in comparing results from different studies
      using this biomarker.

PMID- 10955716
TI  - Apoptosis in skin pigment cells of the medaka, Oryzias latipes (Teleostei),
      during long-term chromatic adaptation: the role of sympathetic innervation.
AB  - Many teleost fish can adapt their body color to a background color by changing
      the morphology and density of their skin pigment cells. Melanophore density in
      fish skin decreases during long-term adaptation to a white background. Although
      cell death, especially apoptosis, is thought to be involved in these
      morphological changes, there are no data clearly supporting this mechanism. Using
      medaka fish, Oryzias latipes, we observed that, on a white background,
      melanophore size was reduced first and this was followed by a decrease in
      melanophore density caused by gradual cell death. The process of cell death
      included loss of cell activity, cell fragmentation, phagocytosis of the
      fragments, and clearance via the epidermis. Apoptosis was assessed by the
      appearance of phosphatidylserine on the cell surface of melanophores that had
      lost motile activity, and DNA fragments involved in cell fragmentation were
      detected by the TUNEL (TDT-mediated dUTP-biotin nick end-labeling) assay.
      However, when chemically denervated fish were used, although melanophore size was
      reduced as expected, cell death was suppressed even on a white background. In
      skin tissue culture, apoptosis in melanophores was stimulated significantly by
      norepinephrine, but not by melanin-concentrating hormone. These results indicate
      that melanophore density decreases by apoptosis, and suggest that sympathetic
      innervation has an important role in the regulation of apoptosis in melanophores.
      In analogous fashion, leucophores showed a significant decrease in density with
      an increase of cell death on a black background. We suggest that apoptosis
      regulates the balance of pigment cells in the skin of medaka fish to adapt their
      body color to a particular background.

PMID- 10955718
TI  - Changes in the expression of the nerve growth factor receptors TrkA and p75LNGR
      in the rat thymus with ageing and increased nerve growth factor plasma levels.
AB  - The nerve growth factor (NGF) receptors p75LNGR and TrkA are expressed by thymic
      epithelial cells. Presumably, the NGF-TrkA system is involved in the paracrine
      communication between thymic epithelial cells and thymocytes, whereas the
      functional role of p75LNGR is still unknown. The thymus of vertebrates undergoes
      age-related changes that in part depend on hormonal factors. In order to find out
      whether thymic epithelial cells are responsive to NGF during the whole lifespan
      of the rat, we studied NGF receptor expression in the thymus from birth to 2
      years of age, using immunohistochemistry. Furthermore, to evaluate whether
      increased plasma levels of NGF affected the ageing process, either NGF or 4
      methylcatechol (4MC), an inductor of NGF synthesis, was administered. Both TrkA
      and p75LNGR were expressed by a subpopulation of thymic epithelial cells during
      the whole age range studied and their expression peaked at around 3 months. TrkA
      was primarily found in subcortical and medullary epithelial cells, whereas
      p75LNGR was seen in a subpopulation of medullary cells. Cortical epithelial
      cells, neural crest-derived cells, other stromal cells and thymocytes were not
      immunoreactive for NGF receptors. Neither the administration of NGF nor the
      increased NGF plasma levels obtained after 4MC treatment seemed to affect the
      ageing of the thymus as assessed by morphological and immunohistochemical
      criteria, but this increase in NGF levels did produce a shift in the expression
      of p75LNGR from epithelial cells to ED1-positive macrophages in animals of 6
      months and older. Present results indicate that the expression of p75LNGR and
      TrkA in the rat thymus undergoes age-dependent changes that parallel those of
      epithelial cells. NGF could therefore be important for thymus homeostasis,
      possibly acting on epithelial cells. Nevertheless, NGF did not seem to be able to
      prevent the involution of this organ, although it produced a switch in the
      expression of p75LNGR, the significance of which remains to be established.

PMID- 10955717
TI  - Ezrin, a membrane-organizing protein, as a polarization marker of the retinal
      pigment epithelium in vertebrates.
AB  - Immunoreactivity for ezrin, a membrane-organizing phosphoprotein that tethers
      actin microfilaments to cell membrane proteins, was evaluated as a polarization
      marker in the intraocular neuroepithelial cells of vertebrates, especially in the
      retinal pigment epithelium (RPE). Six fetal human eyes representing the 14th-28th
      gestational weeks, 9 normal adult eyes, 12 eyes with intraocular tumors, and 26
      eyes from 15 other vertebrate species were analyzed by immunohistochemistry using
      the avidin-biotinylated peroxidase complex (ABC) method and monoclonal antibody
      (mAb) 3C12 to ezrin. The apical cytoplasm and microvilli of the human RPE always
      reacted with mAb 3C12, but the basal cytoplasm was labeled in reactive RPE only.
      In autopsy eyes and if fixation was delayed, ezrin immunoreactivity in RPE was
      more diffuse. Developing RPE became gradually immunoreactive from the 14th week
      of gestation onward. The microvilli of the baboon, pig, raccoon dog, cow, and rat
      RPE cells were likewise labeled, and their basal cytoplasm was variably
      immunoreactive as well, but the microvilli of the avian RPE did not react with
      the antibody used. In all six mammals mentioned, both layers of the ciliary
      epithelium and the anterior iris epithelium reacted for ezrin, and the posterior
      epithelium was weakly labeled in pig, cow, and rat eyes. Normal peripheral and
      reactive human retina, and normal baboon, pig, raccoon dog, cow, rat, black
      grouse, and jay eyes, showed immunoreaction for ezrin in Muller cells, usually in
      their microvilli. Ezrin is widely found in RPE and anterior segment
      neuroepithelia of the mammalian eye, in which it may segregate membrane proteins
      to specific membrane surfaces, especially to the apical microvilli of the RPE,
      which intimately interact with outer segments of photoreceptor cells. The ezrin
      gene on human chromosome 6q25-26 is consequently a candidate gene for causing
      retinal degenerations.

PMID- 10955719
TI  - Morphological and functional development of the thyroid tissue in rainbow trout
      (Oncorhynchus mykiss) embryos.
AB  - The development of the thyroid tissue in rainbow trout (Oncorhynchus mykiss)
      embryos between 20 and 88 days postfertilization (dpf) was studied using
      traditional histological methods in combination with immunostaining using
      antibodies raised against L-thyroxine (T4) and triiodo-L-thyronine (T3). In 20
      dpf embryos, the thyroid primordium appeared as a simple tube aligned with the
      dorsal surface of the ventral aorta. The tubular primordium becomes progressively
      bifurcated at each end and follicles are formed by pinching off balls of cells
      from the tips of the bifurcations. The secretory activity of the thyroid tissue
      appears first as a synthesis phase, evident at 30 dpf, characterized by T4 and T3
      immunostaining present only in the follicle lumen. A later hormone release or
      secretory phase was first evident for T4 immunostaining at 43 dpf and for T3
      immunostaining at 46 dpf and was characterized by the presence of immunostaining
      both within the follicle lumen and also in the cytoplasm of some (but not all)
      thyrocytes. This stage was also coincident with a marked increase in the number
      of pituitary thyrotrophs. The proportion of embryos exhibiting immunostained
      thyrocytes increased progressively from 43 to 52 dpf, at which stage all embryos
      had T4- and T3-immunostained thyrocytes.

PMID- 10955720
TI  - Two-color double-labeling in situ hybridization of whole-mount Hydra using RNA
      probes for five different Hydra neuropeptide preprohormones: evidence for
      colocalization.
AB  - The freshwater polyp Hydra magnipapillata has a primitive nervous system that
      produces at least three distinct classes of neuropeptides: various peptides
      having the C-terminal sequence Arg-Phe-NH2 (the Hydra-RFamide family), Leu-Trp
      NH2 (the Hydra-LWamide family), and a single peptide having the C-terminal
      sequence Lys-Val-NH2 (Hydra-KVamide). The various Hydra-RFamides are synthesized
      by three different preprohormones: preprohormone-A, -B, and -C. The various Hydra
      LWamides are synthesized by a single preprohormone (prepro-Hydra-LWamide), as is
      Hydra-KVamide (prepro-Hydra-KVamide). Using a wholemount double-labeling two
      color in situ hybridization technique and RNA probes specific for each of these
      five Hydra preprohormone mRNAs, we found that specific sets of neurons express
      each of the five preprohormones, except for the peduncle region of Hydra (an area
      just above the basal disk), where a population of neurons exists that expresses
      both preprohormones-A and preproHydra-KVamide mRNAs. The functional significance
      of this coexpression is unclear. This is the first report on the coexpression of
      two well-characterized preprohormones (yielding two well-characterized
      neurohormone families) in cnidarians. This report also shows that there are at
      least six neurochemically different populations of neurons in Hydra.

PMID- 10955721
TI  - Expression of synaptic vesicle trafficking proteins in the developing rat pineal
      gland.
AB  - Adult mammalian pinealocytes contain several synaptic membrane proteins that are
      probably involved in the regulation of targeting and exocytosis of synaptic-like
      microvesicles (SLMVs). Immunohistochemical techniques have now demonstrated the
      spatiotemporal expression pattern of some of these proteins during rat pineal
      ontogenesis. Various synaptic vesicle trafficking proteins are detectable in
      proliferating epithelial cells of the pineal anlage even at embryonic day 17.5 (E
      17.5), with the exception of syntaxin I (weakly expressed from E 19.5) and
      dynamin I (whose levels increase markedly during the first postnatal week).
      Numerous cells exhibiting strong immunoreactivity for synaptobrevin II, SNAP-25,
      synaptophysin, and munc-18-1 are distributed throughout the increasingly compact
      gland at E 19.5 and E 20.5; however, their number declines toward the proximal
      deep part of the organ. Groups of postmitotic cells situated at the surface of
      the developing gland exhibit marked immunoreactivity for the aforementioned
      proteins and lie close to the laminin-immunoreactive outer limiting basement
      membrane or to its remnants in regions of basement membrane dissolution. We also
      show that synthesis of vimentin and S-antigen seems to begin earlier during
      pineal development than previously recognized. Thus, synaptic vesicle trafficking
      proteins are the earliest molecular markers of pinealocyte differentiation known
      to date, being expressed well before the onset of rhythmic hormone secretion in
      the pineal gland, where they may play a role in morphogenetic events. Components
      of the extracellular matrix such as laminin may be critically involved in the
      upregulation of synaptic membrane protein expression. The dynamin immunostaining
      pattern indicates that SLMVs of pinealocytes begin to undergo regulated cycles of
      exo/endocytosis during postnatal week 1.

PMID- 10955722
TI  - Phagocytosis of dying chondrocytes by osteoclasts in the mouse growth plate as
      demonstrated by annexin-V labelling.
AB  - Endochondral ossification in the epiphyseal growth plate of long bones is
      associated with programmed cell death (PCD) of a major portion of the
      chondrocytes. Here we tested the hypothesis that at the ossification front of the
      epiphyseal growth plate osteoclasts preferentially phagocytose chondrocytes that
      are undergoing PCD. We injected biotin-labelled annexin-V (anx-V-biotin, an early
      marker of PCD) intravenously in young adult mice. After 30 min of labelling, long
      bones were recovered and the tissue distribution examined of anx-V-biotin
      labelled cells in the growth plate using ABC-peroxidase histochemistry. Positive
      staining for anx-V-biotin was detected in hypertrophic chondrocytes still present
      in closed lacunae at some distance from the ossification front. At the
      ossification front, chondrocyte lacunae were opened and close contacts were seen
      between tartrate-resistant acid phosphatase-positive osteoclasts and hypertrophic
      cartilage cells. Osteoclasts were significantly more frequently in contact with
      anx-V-biotin-labelled chondrocytes than with unlabelled chondrocytes. Osteoclasts
      also contained labelled and unlabelled phagocytic fragments within their
      cytoplasm. We conclude that in the growth plate osteoclasts preferentially
      phagocytose hypertrophic chondrocytes that are dying, suggesting these dying
      cells may signal osteoclasts for their removal.

PMID- 10955723
TI  - Different sublines of Jurkat cells respond with varying susceptibility of
      internucleosomal DNA degradation to different mediators of apoptosis.
AB  - The ability of two different Jurkat sublines, termed standard and JM, to form DNA
      ladders was investigated after various apoptotic stimuli. Exposure to a broad
      spectrum of drugs interfering with signal transduction or cellular metabolism
      revealed distinct differences between both Jurkat sublines with regard to the
      pattern of DNA degradation. In standard Jurkat cells, internucleosomal DNA
      cleavage occurred only after treatment with the protein kinase inhibitor
      staurosporine. In contrast, the JM subline responded with internucleosomal DNA
      fragmentation to exposure to gemcitabine, cycloheximide or staurosporine. All
      drugs induced the formation of DNA fragments of about 50 kb in both sublines, as
      revealed by pulse field electrophoresis, except H2O2, which caused unspecific DNA
      degradation. The staurosporine-induced DNA ladder formation was accompanied by an
      increase in caspase-3 activity in both lines which, however, was considerably
      lower in Jurkat JM cells after gemcitabine or cycloheximide exposure. When the
      analysis of internucleosomal DNA degradation was carried out after mycoplasma
      infection, both Jurkat lines responded with DNA ladder formation after exposure
      to all drugs used (here only shown for the standard subline). Employing the
      zymogram technique, nuclease activities of 47 kDa and 54 kDa were detected in
      culture supernatants, cell homogenates and nuclear extracts only when mycoplasma
      infected, whereas the samples obtained from mycoplasma-free sublines were
      nuclease-negative using this technique, indicating that these endonucleases were
      of mycoplasmal origin. After drug exposure, the mycoplasmal nucleases must have
      gained access to the cytoplasm and nuclei of their host cells by an unknown
      mechanism.

PMID- 10955724
TI  - Ultrastructural analysis of the transdifferentiation of smooth muscle to skeletal
      muscle in the murine esophagus.
AB  - The ultrastructure of the mouse esophagus at the level of the diaphragm was
      studied from embryo day 17 to adult. The transdifferentiation of smooth muscle
      into skeletal muscle was categorized into seven ultrastructural stages: during
      phase I normal smooth muscle myogenesis was observed. In phase II subpopulations
      of cells changed into aggregates of myoblast-like cells. At the center of these
      cell aggregates, phase III cells appeared that contained condensed myofilaments.
      Dense bodies and dense bands appeared enlarged by the accumulation of thin
      filaments. In phase IV the condensed myofilaments organized into sarcomere
      pretemplate structures. The dense bodies and dense bands formed rudimentary Z
      lines. In phase V the sarcomere templates appeared as more defined structures and
      began to align. An elaborate perinuclear region appeared. During phase VI,
      skeletal muscle sarcomeres were apparent and myofilaments were arranged in a
      typical hexagonal array. Phase VII skeletal muscle fibers were unique with
      sarcomeric bifurcations and anastomoses between adjacent myofibrils. Non
      contractile organelles were less organized in these cells than in skeletal
      muscles such as rectus and vastus lateralis muscles. During the
      transdifferentiation process, other cell types remained unchanged, except the
      number of interstitial cells of Cajal became reduced. Immunocytochemical studies
      with antibodies against smooth and skeletal muscle myosin were also performed
      during the process of transdifferentiation. An osmium tetroxide/potassium
      ferricyanide en bloc mordant enabled the use of ultrathin Unicryl sections for
      immunocytochemistry. Cells exhibited smooth muscle myosin-like immunoreactivity
      from the smooth muscle stage through the condensed myofilament stage. Cells were
      immunopositive for skeletal muscle myosin before the formation of sarcomere
      templates, during the condensed stage, and after development of mature skeletal
      muscle cells. We also observed a hybrid muscle cell with properties of both
      smooth and skeletal muscle cells.

PMID- 10955725
TI  - Silica deposition in Demosponges: spiculogenesis in Crambe crambe.
AB  - Transmission electron-microscopy images coupled with dispersive X-ray analysis of
      the species Crambe crambe have provided information on the process of silica
      deposition in Demosponges. Sclerocytes (megasclerocytes) lie close to spicules or
      surround them at different stages of growth by means of long thin enveloping
      pseudopodia. Axial filaments occur free in the mesohyl, in close contact with
      sclerocytes, and are triangular in cross section, with an internal silicified
      core. The unit-type membrane surrounding the growing spicule coalesces with the
      plasmalemma. The axial filament of a growing spicule and that of a mature spicule
      contain 50%-70% Si and 30%-40% Si relative to that contained in the spicule wall,
      respectively. The extracellular space between the sclerocyte and the growing
      spicule contains 50%-65%. Mitochondria, vesicles and dense inclusions of
      sclerocytes exhibit less than 10%. The cytoplasm close to the growing spicule and
      that far from the growing spicule contain up to 50% and less than 10%,
      respectively. No Si has been detected in other parts of the sponge. The
      megascleres are formed extracellularly. Once the axial filament is extruded to
      the mesohyl, silicification is accomplished in an extracellular space formed by
      the enveloping pseudopodia of the sclerocyte. Si deposition starts at regularly
      distributed sites along the axial filament; this may be related to the highly
      hydroxylated zones of the silicatein-alpha protein. Si is concentrated in the
      cytoplasm of the sclerocyte close to the plasmalemma that surrounds the growing
      spicules. Orthosilicic acid seems to be pumped, both from the mesohyl to the
      sclerocyte and from the sclerocyte to the extracellular pocket containing the
      growing spicule, via the plasmalemma.

PMID- 10955726
TI  - Distribution of brominated compounds within the sponge Aplysina aerophoba:
      coupling of X-ray microanalysis with cryofixation techniques.
AB  - The major secondary metabolites of the sponge Aplysina aerophoba are brominated
      compounds. X-ray energy dispersive microanalysis was therefore used to locate
      secondary metabolites via the Br signal in energy emission spectra from sponge
      sections. To test the reliability of this method in the face of the loss or
      redistribution of metabolites during processing, we compared the results obtained
      by conventional aldehyde fixation with those obtained by cryofixation and
      cryosubstitution with and without cryoembedding. Bromine appeared to be
      concentrated in two sponge structures, viz. fibres and spherulous cells, when
      cryofixed material was examined. However, X-ray microanalysis failed to
      demonstrate the presence of bromine in spherulous cells in chemically fixed
      samples, showing the need for cryotechniques to avoid the loss of compounds.
      Cryofixation plus cryosubstitution methods performed best regarding structural
      preservation and the immobilization of metabolites. The presence of bromine in
      the spherulous cells suggests that this cell type is the producer of the
      secondary metabolites, as described for other sponge species. Nevertheless, the
      presence of bromine in sponge fibres indicates that they can accumulate metabolic
      substances, although we have been unable to assess whether the chemicals are in
      their original form or in a modified state within the fibres. A. aerophoba has
      both bacterial and cyanobacterial symbionts in its mesohyl; the absence of
      brominated compounds in them contrasts with previous findings in other sponges
      with prokaryote symbionts.

PMID- 10955727
TI  - Connexin 43 expression is downregulated in raft cultures of human keratinocytes
      expressing the human papillomavirus type 16 E5 protein.
AB  - A decrease in gap junction-mediated cell-to-cell communication has previously
      been observed in monolayer cultures of human keratinocytes (HaCaT cells)
      expressing the human papillomavirus type 16 E5 (HPV16 E5) gene and attributed to
      the reduced phosphorylation of connexin 43, the most abundant connexin in HaCaT
      cells. In line with this observation, we have now analyzed the effect of HPV16 E5
      on connexin 43 expression in raft cultures produced by transfected HaCaT cells.
      These keratinocytes transcribe HPV16 E5 under the control of a dexamethasone
      inducible promoter. Our results show that treatment with dexamethasone leads to
      an almost complete disappearance of connexin 43 in rafts expressing the E5 gene
      but not in control rafts. In our study we discuss the possible effects of this
      downregulation on cell-cell communication and cellular malignant transformation.

PMID- 10955728
TI  - Gastroduodenal lesions in familial adenomatous polyposis.
AB  - Prophylactic colectomy is generally recommended for patients with familial
      adenomatous polyposis (FAP) who are inevitably affected with large bowel cancer.
      After prophylactic colectomy has been performed, gastrointestinal malignancy is
      the leading cause of death. Duodenal adenomas are found in patients with FAP and
      the adenoma-carcinoma sequence exists in the FAP duodenum, suggesting that
      treatment of duodenal polyps might be beneficial. Several methods of treatment
      for duodenal lesions in patients with FAP have been reported, but the current
      treatment options are not ideal. The nonsteroid anti-inflammatory drugs, sulindac
      and aspirin, are used for chemoprevention, while recently developed
      cyclooxygenase-2 inhibitors may be of some use in the future. Endoscopic
      polypectomy has been attempted for duodenal polyps and open surgical polypectomy
      has proven to be effective for selected patients. Photodynamic therapy and Argon
      plasma coagulation may be suitable to treat carpeted polyposis. New methods of
      duodenal resection, such as pancreas-preserving duodenectomy and pylorus
      preserving pancreaticoduodenectomy, might be considered for severe duodenal
      polyposis; however, because prophylactic duodenal surgery has been considered too
      aggressive, surveillance duodenoscopy is usually performed to detect duodenal
      cancer at an early stage.

PMID- 10955729
TI  - Nitrite/nitrate (NOx) levels and hemodynamics during septic shock.
AB  - Nitric oxide (NO) acts as a vasorelaxant. We investigated the relationship
      between nitrite/nitrate (NOx), which are the final metabolites of NO, and
      hemodynamics during septic shock. We also examined tumor necrosis factor alpha
      (TNF-alpha), interleukin-8 (IL-8), and endotoxin. A significant negative
      correlation was observed between NOx levels and pulmonary capillary wedge
      pressure (PCWP; r = -0.6075, P = 0.0028). A significant positive correlation was
      noted between NOx levels and the cardiac index (CI; r = 0.5934, P = 0.0038). A
      significant negative correlation was found between NOx levels and the systemic
      vascular resistance index (SVRI; r = -0.4354, P = 0.0485). A significant positive
      correlation was observed between NOx levels and the stroke volume index (SVI; r =
      0.5040, P = 0.0186). A significantly close positive correlation was also observed
      between TNF-alpha levels and NOx levels (r = 0.7848, P < 0.0001). These findings
      suggest that NOx levels are closely associated with hemodynamics during septic
      shock, resulting in a vascular relaxing effect.

PMID- 10955730
TI  - An increase in macrophage migration inhibitory factor release in patients with
      cardiopulmonary bypass surgery.
AB  - To determine the macrophage migration inhibitory factor (MIF) responses to
      cardiopulmonary bypass (CPB) surgery as well as to investigate their roles in
      predicting patient outcome, a prospective, observational, pilot study was
      performed. Thirty patients undergoing cardiovascular surgery with CPB received
      10mg/kg betamethasone immediately before the CPB. Ten normal healthy volunteers
      served as control subjects. Blood samples were serially obtained for 24h and
      assayed for MIF, cortisol, and tumor necrosis factor alpha (TNF-alpha). TNF-alpha
      release could not be detected during the study period. Compared with both the
      control and baseline values, the MIF and cortisol levels were elevated before CPB
      and peaked at the end of CPB (57.5 +/- 4.8 ng/ml, P < 0.0001), and at the end of
      the surgery (507.7 +/- 44.1 nmol/l, P < 0.0001), respectively. Peak MIF levels
      correlated with aortic cross-clamp time (r2 = 0.183, P = 0.0182, n = 30), but did
      not show a significant correlation with peak cortisol levels. The levels of MIF
      tended to be 40%-50% higher during CPB in patients with longer intensive care
      unit (ICU) stays and in those with organ dysfunction than in those with short ICU
      stays and no organ dysfunction. All patients were discharged from the ICU. In
      conclusion, our findings demonstrate that MIF production occurs in patients with
      CPB surgery. When high-dose steroids are administered, high MIF levels were found
      to only slightly affect the patient morbidity and outcome after CPB surgery.

PMID- 10955731
TI  - Allelic loss on 17p13 (TP53) and allelic loss on 3p21 in early squamous cell
      carcinoma of the lung.
AB  - Roentgenographically occult bronchogenic squamous cell carcinomas are early lung
      cancers that localize in the bronchial wall, and are thought to be a good model
      to elucidate the carcinogenesis of lung cancer. In the present study, we analyzed
      the incidence of allelic losses on chromosome regions 3p21 and 17p13 in 40 cases
      of roentgenographically occult bronchogenic squamous cell carcinomas, using three
      microsatellite dinucleotide polymorphic markers. We also investigated the
      relationship between such allelic loss and the clinicopathological findings of
      those cases. These chromosome regions showed frequent losses. Moreover, the
      incidence of loss on 17p13 increased gradually along with the advance of the
      depth of invasion, while the incidence of loss on 3p21 increased along with the
      advancing length of the longitudinal extension. These results suggested that
      these chromosome regions play different roles in lung cancer progression, i.e.,
      the 3p21 chromosome region was related to the longitudinal extension of the
      carcinoma while the 17p13 (p53) region was related to the depth of invasion.

PMID- 10955732
TI  - D3 lymph node dissection in gastric cancer: evaluation of postoperative mortality
      and complications.
AB  - Since November 1995 we have been performing a D3 lymph node dissection in
      patients undergoing an operation for gastric cancer with a curative intent. The
      aim of the present study was to evaluate whether this procedure results in an
      increased postoperative mortality or complication rate in a Western population.
      Between November 1995 and August 1997 the postoperative courses of 76 patients
      were retrospectively assessed (45.3 lymph nodes per patient, lymph node ratio:
      0.16). The patient outcome was compared with data from a historic control group
      of patients (n = 383) in whom the newly established D2 dissection was studied in
      our department. Regarding the demographic, clinical, and tumor-pathologic data,
      and the choice of resection and reconstructive procedures, the two groups
      differed only slightly. The postoperative mortality of 1% was lower (vs 6.8%)
      while the overall complication rate of 34% (vs 32.1%) was identical. In
      particular, no anastomotic leakage (vs 9.4%) and fewer nonsurgical complications
      (17.1% vs 27.9%) occurred. The reoperation rate was 1% vs 9.7%. However, in 6% of
      the patients drainage tubes had to be inserted under computed tomographic
      guidance. The average hospital stay remained unchanged (21.9 vs 20.7 days). A D3
      dissection was shown to be feasible while demonstrating no disadvantages in the
      patients when compared with the D2 procedure.

PMID- 10955733
TI  - Correlation between the expression of methionine adenosyltransferase and the
      stages of human colorectal carcinoma.
AB  - Methionine adenosyltransferase (MAT) catalyzes the synthesis of S
      adenosylmethionine (AdoMet) from ATP and L-methionine. AdoMet is the major methyl
      donor in most transmethylation reactions in vivo, and it is also the propylamino
      donor in the biosynthesis of polyamines. In the present study, we assessed MAT
      activity in human colons with colorectal carcinoma and the values were compared
      with those of morphologically normal adjacent mucosa. Higher levels of MAT
      activity were observed in the colorectal carcinoma than in the normal colon. The
      ratio of MAT activity in tumor tissue versus normal tissue seemed to be
      correlated well will the stage of the colorectal tumor. Furthermore, immunoblot
      analysis showed that the high levels of MAT activity observed in colorectal
      carcinoma were due to the increased amounts of MAT protein. Immunohistochemical
      analysis revealed that MAT was most abundant in goblet cells, particularly in
      granules in the supranuclear area of these cells. In the colorectal carcinoma
      tissues, MAT was strongly stained in the cancerous cells and localized in
      granules in the supranuclear region. The results of this preliminary study
      suggest that determination of the relative ratio of MAT activity in both normal
      and tumor regions in human colorectal carcinoma could be a clinically useful tool
      for determining the stage of malignancy of colorectal carcinomas.

PMID- 10955735
TI  - Synchronous or metachronous double cancers of the pancreas and other organs:
      report on 12 cases.
AB  - Pancreatic carcinoma carries a poor prognosis, especially invasive ductal
      carcinoma of the pancreas. This retrospective study describes the results of the
      treatment and prognosis for double cancers in which cancer of the pancreas was
      associated with malignancies in other organs in 12 patients who were diagnosed
      and treated at Kurume University Hospital. The patients included 4 women and 8
      men, with an average age of 67 years. Of the 12 tumors, 7 were metachronous
      pancreatic cancers which occurred after resections of other organ malignancies.
      Five patients had synchronous double cancers, one of whom was diagnosed to have
      gastric cancer on admission. Two other patients of this group were diagnosed to
      have lung cancer, while the remaining 2 patients suffered from colon cancer. By
      the time pancreatic cancer was diagnosed, gastrectomies had been performed in 7
      patients for either gastric cancer or ulcers. In addition, one patient underwent
      a hysterectomy for uterine carcinoma and another received a low anterior
      resection for rectal carcinoma. Four of 5 patients in the synchronous group had
      nonresectable tumors and a palliative bypass operation was performed in 2 of
      these patients. Six patients who had metachronous double cancers died because of
      pancreatic cancer recurrence or metastases. We conclude that the prognosis of
      double cancers, where cancer of the pancreas is associated with other organ
      malignancies, primarily depends on the prognosis of the pancreatic carcinoma, and
      the present study suggests the necessity of long-term follow-up examinations for
      gastrectomy patients in order to make an early diagnosis of pancreatic cancer.

PMID- 10955734
TI  - Variations in the expression of platelet-derived endothelial cell growth factor
      in human colorectal polyps.
AB  - Platelet-derived endothelial cell growth factor (PD-ECGF) has been identified to
      be an angiogenic factor, and a close relationship between the expression of PD
      ECGF and tumor development has been postulated. This study was designed to assess
      both the role of PD-ECGF in human colorectal polyps as well as its relationship
      to the expression of other oncogenes during colorectal carcinogenesis. One
      hundred twenty patients with colon polyps who had undergone a polypectomy were
      studied. The polyps were classified based on the pathological findings as
      nonneoplastic or sporadic adenoma. The polyps were immunostained for PD-ECGF and
      vascular endothelial cell growth factor (VEGF), as well as for Ki-67 antigen and
      p53. The correlations between expression of PD-ECGF and clinicopathologic factors
      were examined. PD-ECGF was expressed at significant levels only in adenomas: in 4
      of the 20 polyps with severe dysplasia (20%), and in 5 of the 20 cases of
      carcinoma in adenoma (25%). PD-ECGF was not detected in the nonneoplastic polyps
      and in adenomas with low-grade dysplasia. The intensity of immunostaining for PD
      ECGF in adenomas correlated with the expression of Ki-67 antigen (P < 0.001) but
      not with that of p53. VEGF was not detected in any types of polyps. Angiogenic
      factors in colorectal adenomas might play an important role in carcinogenesis.
      The correlated expression of PD-ECGF and Ki-67 antigen suggests that PD-ECGF
      might not only act as an angiogenic factor, but also as a tumor growth factor.

PMID- 10955736
TI  - Management of nodular goiters and their operative indications.
AB  - It remains controversial whether or not nodular goiters should be treated
      surgically or conservatively. This report reviews our 9-year experience of
      treating nodular goiters in 334 patients, 44 of whom underwent surgery, and
      compares the methods of treatment employed from 1990 to 1999 with those employed
      from 1971 to 1989 when 171 operations were carried out. In accordance with
      diagnoses made using fine-needle aspiration biopsy (FNAB) and ultrasonography,
      patients were treated as follows. Those with cysts were given percutaneous
      ethanol injection therapy (PEIT), and those with solid tumors underwent surgery
      if cancer of >class 3 was suspected or if the tumors were >3 cm. Consequently, 44
      patients with solid tumors underwent surgery and 72 with cysts were treated by
      PEIT. The number of operations performed annually decreased to half of the pre
      1990 figure. During the follow-up of those patients who did not undergo surgery,
      four with solid tumors and two with cysts later required surgery due to suspected
      carcinoma of >class 3 in 3 patients or as a result of personal choice in 3
      patients. The growth of solid tumors was not able to be measured in most cases.
      These results indicate that the number of operations performed for nodular
      goiters can be reduced by PEIT. An accurate cytological diagnosis supports this
      therapeutic strategy.

PMID- 10955737
TI  - The time course of elastin fiber degeneration in a rat aneurysm model.
AB  - Previous findings vary regarding the timing and cause of elastin fiber
      degeneration in the elastase-induced rat abdominal aortic aneurysm model. We
      examined the timing and cause of elastin fiber degeneration after elastase
      infusion using two different elastase infusion times. Twenty-four Sprague-Dawley
      rats were divided into two groups. The infrarenal abdominal aorta was infused
      with 15 U of elastase for 15 min (n = 12, 15-min infusion group) or 30 min (n =
      12, 30-min infusion group). In each group, three rats were killed immediately and
      1, 3, and 7 days after infusion, and then the aortas were excised for a
      histologic examination. Elastin fibers did not stain, even immediately after
      elastase infusion, in the 30-min infusion group. The degeneration of elastin
      fibers did not progress in the 15-min infusion group during the period of
      observation. Inflammatory cells infiltrated mainly to the adventitia near regions
      where the degeneration of elastin fibers spread totally through the aortic media.
      Elastin fibers degenerate immediately after elastase infusion and thus seem to
      degenerate not due to endogenous proteinases that are produced by the
      infiltrating cells, but due to the exogenously infused elastase itself.
      Inflammatory cell infiltration was thus found to be a result of the degeneration
      of elastin fibers in this model.

PMID- 10955738
TI  - Ruptured sinus of a Valsalva aneurysm associated with autosomal-dominant
      polycystic kidney disease in an elderly patient: report of a case.
AB  - We report herein the case of a 71-year-old woman with autosomal-dominant
      polycystic kidney disease (ADPKD), who was referred to our hospital for
      investigation of facial edema. Echocardiography demonstrated a large aneurysm
      arising from the non-coronary sinus of Valsalva, with a left to right shunt and
      jets of blood passing from the aneurysm toward the septal leaflet of the
      tricuspid valve. Surgical treatment was successfully carried out by resecting the
      aneurysmal wall and performing a patch closure of the orifice. It is well known
      that ADPKD predisposes patients to cardiovascular disease, and this case report
      serves to demonstrate that when a patient with ADPKD presents with progressive
      heart failure, the possibility of a ruptured sinus of a Valsalva aneurysm must be
      considered.

PMID- 10955739
TI  - Synchronous multiple primary cancers of the stomach and duodenum in aged
      patients: report of two cases.
AB  - We describe herein the cases of two aged patients found to have synchronous
      multiple primary cancers of the stomach and duodenum. The first patient was an 82
      year-old man who was preoperatively diagnosed as having gastric cancer after
      presenting with signs of pyloric stenosis. At laparotomy, duodenal cancer was
      incidentally found to have infiltrated the transverse colon. A
      pancreatoduodenectomy and right hemicolectomy with radical lymph node dissection
      was performed. Two early well-differentiated adenocarcinomas of the stomach and
      an advanced poorly differentiated adenocarcinoma of the duodenum were confirmed.
      This patient is now well without any evidence of recurrence more than 5 years
      after surgery. The second patient was a 77-year-old man who was also diagnosed as
      having gastric cancer after presenting with signs of pyloric stenosis.
      Preoperatively, duodenal cancer was detected by endoscopy. A
      pancreatoduodenectomy and partial colectomy with radical lymph node dissection
      was performed because the duodenal cancer was suspected of having infiltrated the
      transverse colon. An early moderately differentiated adenocarcinoma of the
      stomach and an advanced moderately differentiated adenocarcinoma of the duodenum
      were confirmed, but the duodenal cancer was not seen to invade the transverse
      colon microscopically. This patient died of cancer 7 months after surgery.
      Because multiple primary cancers commonly develop in elderly patients, a precise
      preoperative diagnosis must be made and optimal treatment applied.

PMID- 10955740
TI  - Encapsulated pericardial fat necrosis treated by video-assisted thoracic surgery:
      report of a case.
AB  - A 55-year-old moderately obese man who was admitted to a local hospital following
      a traffic accident reported having experienced an episode of sharp and sudden
      pleuritic pain in the left anterior lower chest 2 days earlier. A computed
      tomographic scan on admission demonstrated a nonhomogeneous mass in the anterior
      left side of the chest, abutting the left cardiac margin, and a left-sided
      pleural effusion. As a mediastinal tumor was suspected, he was referred to our
      hospital for investigation and treatment. An exploratory thoracotomy was
      performed by video-assisted thoracic surgery (VATS) about 3 weeks later, which
      revealed a firm, yellowish mass on the oral side of the pericardial fat pad,
      adhering to the anterior chest wall. The mass was easily removed. The resected
      specimen consisted of a lobulated fragment of adipose tissue measuring 5.0 x 3.5
      x 2.0 cm, and the final pathologic diagnosis was pericardial fat necrosis. The
      patient had an uneventful postoperative recovery and has remained free of
      symptoms for 10 months since his operation. Pericardial fat necrosis remains a
      rare clinical entity. Surgical excision by VATS achieves symptomatic cure and
      probably continues to be the treatment of choice because of the need to exclude a
      neoplasm in the differential diagnosis.

PMID- 10955741
TI  - Endobronchial metastasis from renal cell carcinoma: report of a case.
AB  - A case of endobronchial metastasis from renal cell carcinoma developing 5 years
      after a right nephrectomy in a 63-year-old man is reported. Bronchoscopic
      examination performed after the patient presented with hemoptysis showed a
      polypoid tumor obstructing the entrance to the left upper bronchus. A snare was
      introduced through a bronchofiberscope to remove the endobronchial tumor,
      following which his atelectasis improved remarkably and his hemoptysis resolved.
      No side effects were observed. Electrosurgical snaring proved useful as
      palliative treatment to relieve bronchial obstruction due to an endobronchial
      metastasis in this patient.

PMID- 10955742
TI  - Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) of the
      breast: report of a case.
AB  - We report herein the unusual case of a 35-year-old woman found to have
      angiolymphoid hyperplasia with eosinophilia (ALHE) of the breast. The patient was
      initially referred to our hospital for investigation of a well-circumscribed
      breast lump, 2.5 cm in diameter, and a clinical diagnosis of fibroadenoma was
      made. However, fine-needle aspiration cytology of the lump revealed an admixture
      of lymphocytes and eosinophils. Therefore, the lump was excised and microscopic
      examination showed features of ALHE. No evidence of recurrence of the lump has
      been seen in the 2 years since this excision. To the best of our knowledge, this
      is the first case to be documented of ALHE arising in the breast.

PMID- 10955743
TI  - Massive bleeding from multiple jejunal diverticula associated with an
      angiodysplasia: report of a case.
AB  - We report herein the case of a 70-year-old woman who presented with massive
      bleeding from multiple jejunal diverticula. She was initially admitted to our
      hospital with massive melena. An upper gastrointestinal endoscopic examination
      revealed no bleeding site. Colonoscopy revealed clotted and red blood throughout
      the colon, and a small diverticulum in the ascending colon which was thought to
      be the source of bleeding. Following admission, she was treated conservatively at
      first, but melena continued and the anemia did not improve despite blood
      transfusions. A laparotomy was performed and multiple jejunal diverticula,
      distributed from 10 to 40 cm distal to the ligament of Treitz, were found. A
      segment of the jejunum containing all diverticula was resected. The most distal
      diverticulum contained a clot of blood, but no ulceration was observed. A
      histological examination revealed many dilated blood vessels in the mucosa and
      submucosa of this diverticulum, which were compatible with the findings of
      angiodysplasia. Based on these findings, we believe that angiodysplasia was the
      cause of bleeding from the jejunal diverticula in this case.

PMID- 10955744
TI  - Surgical treatment for graft stenosis after repair of an interrupted aortic arch:
      report of two cases.
AB  - We report herein two cases of patients who underwent successful reoperation for
      graft stenosis after repair of an interrupted aortic arch (IAA). The first
      patient was a 10-year-old girl who suffered from upper limb hypertension 9 years
      after her initial operation. Cardiac catheterization revealed a pressure gradient
      of 55 mmHg across the repaired arch. At reoperation, a left subclavian turndown
      anastomosis was performed, following which the hypertension resolved and a
      cardiac catheterization done 5 years later demonstrated sufficient growth of the
      restored arch with no significant gradient. The second patient was a 17-year-old
      boy who suffered from general fatigue and intermittent hypertension 12 years
      after his initial operation. Cardiac catheterization revealed a gradient of 60
      mmHg across the repaired arch. He underwent an extraanatomic ascending to
      descending aortic bypass employing an additional 18-mm graft, and a postoperative
      cardiac catheterization showed no gradient between the ascending and descending
      aorta. Our experience has shown that IAA should be repaired without prosthetic
      grafts if possible. Although extraanatomic bypass is useful for reducing the
      operative risks at reoperation, a large graft should be used to avoid the need
      for a third operation. For young children expected to outgrow a second graft,
      performing an endogenous anastomosis, such as a left subclavian turndown
      anastomosis, should be considered as an alternative.

PMID- 10955746
TI  - Adverse outcome following transfemoral endovascular stent-graft repair of an
      abdominal aortic aneurysm in a patient with severe liver dysfunction: report of a
      case.
AB  - We describe herein the case of a patient with severe liver failure in whom an
      abdominal aortic aneurysm (AAA) extending to the right iliac artery was
      diagnosed. Because the risk of performing a standard open repair was considered
      too high in this patient, the aneurysm was uneventfully repaired using a
      technique of transfemoral endovascular stent-grafting with femorofemoral bypass
      and occlusion of the left common and right internal iliac arteries.
      Unfortunately, multiorgan failure associated with adult respiratory distress
      syndrome (ARDS) and disseminated intravascular coagulation (DIC) suddenly
      developed on postoperative day (POD) 2 and the patient died on POD 9. Thus,
      although endovascular stent-grafting is generally assumed to be less invasive and
      therefore feasible for high-risk patients, patients with severe liver dysfunction
      may not be suitable candidates.

PMID- 10955745
TI  - Psoas abscess complicating Crohn's disease: report of a case.
AB  - We describe herein the case of a psoas abscess complicating Crohn's disease, and
      present a review of the literature on this unusual disease entity. A 22-year-old
      Japanese man with a 5-year history of Crohn's ileocolitis presented with right
      lower abdominal and hip pain, and a diagnosis of right psoas abscess was
      subsequently made by abdominal computed tomography (CT). Following the
      administration of antibiotics and CT-guided percutaneous drainage of the abscess,
      the patient's symptoms temporarily improved; however, 2 weeks later, the abscess
      cavity was found to have extended around the periarticular tissue of the right
      hip joint. To prevent the development of septic arthritis of the hip joint,
      surgical drainage of the abscess cavity and ileocecal resection were immediately
      performed, after which the patient's condition greatly improved. The resected
      specimen showed Crohn's ileocolitis with an external fistula in the terminal
      ileum which was considered to have caused the psoas abscess. Since psoas abscess
      in Crohn's disease can result in serious complications such as septic arthritis
      of the hip joint if left untreated, aggressive treatment should be initiated
      without delay.

PMID- 10955747
TI  - Correlation between objective measures of airway calibre and clinical symptoms in
      asthma: a systematic review of clinical studies.
AB  - Clinical symptoms are often used as a measure in asthma management, but a variety
      of symptoms and scales are available. The objectives of this systematic review
      were as follows: (a) to present correlations between symptoms and measures of
      airway calibre; (b) to present the scoring systems/ scales used in the
      publications. In the review, more than 10 000 publications were found under the
      key words: asthma and symptom(s). Twenty-one remained when FEV1/PEF, scale/score
      and correlation were added as key words. In summary, no standardized method
      exists for measuring asthma symptoms with respect to severity. This is the case
      for both the symptoms and the scales. There are two recently-developed asthma
      control scales available (one of which has not yet been published and is not
      included in the review).

PMID- 10955748
TI  - Psychological issues in the treatment of asthmatic patients.
AB  - Recently published research contends that anxiety and depression are more common
      in asthmatic patients than in the general population. Particular psychological
      profiles could even be a risk factor contributing to deaths caused by asthma. The
      purpose of our research was to evaluate the anxiety and depression level in a
      population of 80 asthmatic patients who were treated in our department, and to
      judge whether data collected on psychological profiles of these asthmatic
      patients can be of any significance when dealing with their pathology. The study
      consisted of 40 patients suffering from chronic viral hepatitis B or C, and 40
      healthy subjects who served as a control group. Both sets of patients were
      homogeneous with regard to sex, age and education. All subjects were tested for
      anxiety and depression levels with the S.T.A.I. and Zung questionnaires. A
      structured questionnaire was employed to assess the daily approach to living with
      the disease only in asthmatic patients. The anxiety and depression levels were
      noticeably higher in asthmatic patients than in patients with chronic liver
      disease and healthy subjects. In particular, 34 asthmatic patients scored higher
      than the S.T.A.I. cut-off (40/80) and 27 attained the same results in the Zung
      questionnaire. Results from the asthmatic population and healthy subjects
      illustrated that women had a higher incidence of anxiety and depression compared
      to men, although no statistically significant relationship between sex and
      questionnaire results was apparent in patients with liver disease. In the year
      before assessment, hospitalization and emergency treatment due to asthmatic
      exacerbation was correlated in females with a high incidence of anxiety.
      Additionally, the asthmatic population's level of education is significantly
      related to the incidence of anxiety and depression. With higher education,
      incidence of depression and anxiety decreased. This result was not apparent in
      control groups. The results of our study were: (1) we confirmed that asthmatic
      pathology is associated with an increase in incidence of anxiety and depression,
      whose presence and seriousness should be taken into consideration in therapeutic
      programmes when dealing with a patient; (2) we indicated that a specific approach
      towards therapy is crucial when dealing with an asthmatic patient; (3) we
      suggested how important it is to identify categories of patients that require
      more care because of their psychological profile. These findings should provide
      for the optimal use of informational resources with important applications for
      educational programmes and the future treatment of the asthmatic population.

PMID- 10955749
TI  - Exercise-induced bronchoconstriction depends on exercise load.
AB  - Exercise-induced bronchoconstriction (EIB) is often used as a measure of
      bronchial hyperresponsiveness and employed in epidemiological studies. Different
      tests are used, including free running tests with poor standardization of
      exercise load. The present study aimed to assess the role of exercise load in
      relationship to level of EIB. METHODS: 20 asthmatic children, 9-17 years old with
      a history of EIB, underwent two treadmill test with 85% and 95% exercise load.
      The children ran with increasing speed for the first 2 min until reaching a heart
      rate of 85% or 95% of calculated maximum (220-age) and maintained this speed for
      the last 4 min. Lung function was measured before running, and 0, 3, 6, 10 and 15
      min after the run. Borg scale for perceived exertion was employed for children's
      self-evaluation of exercise load. RESULTS: Peak heart rate, mean Borg score
      during 85% exercise load was 178.7/13.6 and during 95% was 194.3/18.2 (P<0.001).
      Maximum fall in FEV1 after 85% exercise load was 8.84% vs. 25.11% after 95%
      (P<0.001). Nine subjects (40%) fell > or = 10% in FEV1 after 85% exercise load
      vs. 20 subjects (100%) after 95% exercise load. EIB from the 95% exercise load
      test had markedly higher correlation with serum ECP (r=0.77, P<0.001).
      CONCLUSION: Exercise load is essential for the interpretation of EIB, and strict
      standardization of exercise tests should be undertaken. The EIB from the high
      exercise load tests seemed better correlated to inflammatory activity than the
      low exercise load test.

PMID- 10955750
TI  - Helicobacter pylori sero-prevalence in asthma.
AB  - Asthma is a very common respiratory disease which is characterized by the
      presence of cytokine-mediated airway inflammation leading to smooth muscle
      contraction, oedema and progressive airway damage in some cases. In light of our
      recent finding of an increased sero-prevalence of Helicobacter pylori in
      bronchiectasis, we have determined serum levels of H. pylori-specific IgG in
      asthmatic and control subjects. Altogether 90 consecutive asthmatic [mean age +/-
      SD 42.6+/-16 years and 52 female (F)] and 97 healthy control subjects (mean age
      +/- SD 43.2+/-13.3 years and 51 female (F); P = 0.78 and 0.39 respectively) were
      recruited prospectively. H. pylori sero-prevalence was not significantly
      different between asthmatic and control subjects (P>0.05). Serum H. pylori IgG
      levels did not correlate with FEV1 % predicted, FVC % predicted or duration of
      asthma (P>0.05). Similar to the results of previously published sero
      epidemiological studies, there was a weak correlation between serum H. pylori IgG
      with increasing age (r = 0.43, P = 0.004). Despite the sero-epidemiological
      association of H. pylori infection with many inflammatory conditions, our data
      showed no such association for middle age asthmatic patients with mild
      intermittent asthma in our locality.

PMID- 10955751
TI  - Influence of peak expiratory flow monitoring on an asthma self-management
      education programme.
AB  - We assessed whether peak expiratory flow monitoring added to a self-management
      education programme reduced morbidity and improved pulmonary function and
      adherence to treatment in 100 asthma patients (aged 17-65 years) with adequate
      treatment and regular 1-year follow-up. Patients randomized to the experimental
      group used peak expiratory flow readings as the basis for their therapeutic plan
      coupled with educational intervention, whereas patients in the control group
      received the same educational intervention and used symptoms only to guide self
      management. Morbidity parameters, functional status and adherence to medical
      regimens improved in both groups, although the percentage of patients with
      satisfactory adherence was significantly better in the group with peak expiratory
      flow monitoring (83%) than in controls (52%) (P = 0.05). The multivariate
      analysis showed that severity of asthma (odds ratio 9.28, 95% confidence interval
      1.87-45.96, P = 0.006 for moderate asthma) and type of self-management education
      programme (odds ratio: 6.19; 95% confidence interval: 2.04-18.81; P = 0.001 for
      the use of peak expiratory flow readings) were the only independent predictors of
      adherence to treatment. However, a statistically significant association between
      adherence and use of peak expiratory flow monitoring was only found in patients
      with moderate asthma (P = 0.0009). We conclude that peak expiratory flow
      monitorization in optimal conditions (adequate medical regimen, individualized
      self-management education and regular follow-up) showed a beneficial effect on
      adherence to prescribed regimens only in patients with moderate asthma.

PMID- 10955752
TI  - Bronchodilator tolerance and rebound bronchoconstriction during regular inhaled
      beta-agonist treatment.
AB  - There is uncertainty about the development of airway tolerance to beta-agonists
      and the phenomenon of rebound bronchoconstriction on beta-agonist withdrawal. We
      have recently completed a study of the regular terbutaline and budesonide
      treatment in asthma. We report our observations on the effect of starting and
      stopping terbutaline treatment on morning and evening peak flows. The study was a
      randomized four-way, double-dummy, cross-over comparison of regular inhaled
      terbutaline (500-1000 microg four times daily), budesonide, combined treatment
      and matching placebo. Each treatment was given for 6 weeks following a 4 week
      single-blind placebo washout. Ipratropium was used for symptom relief. No other
      asthma medication was permitted during either the treatment or wash-out periods.
      Evaluable data were obtained from 52 subjects for both placebo and terbutaline
      treatment. Changes in mean morning and evening peak flows during terbutaline
      treatment were compared to the baseline peak flows during the last 2 weeks of the
      preceding washout. The peak flow changes on stopping terbutaline were also
      analysed. Mean morning peak flow was not significantly different during
      terbutaline treatment when compared to either baseline or placebo treatment.
      Evening peak flows were significantly higher during terbutaline treatment [mean
      increase 23.1 l min(-1) (95% CI = 18.8, 27.4)]. Analysis of the peak flow changes
      on a day-by-day basis revealed an initial increase in morning peak flows for the
      first 2 days of treatment of 19.2 and 13.41 min(-1) [increases of 25.0 and 17.31
      min(-1) in comparison with the corresponding values during placebo (P<0.01)]
      followed by a return to baseline. The increase in evening peak flows was also
      greater for the first 2 days of treatment than for the remainder of the treatment
      period (P<0.01). On ceasing terbutaline treatment there was a fall in mean
      morning peak flow below the baseline on the following morning of 21.6 l min(-1)
      (P<0.05 compared to placebo). The temporary increase in morning peak flows and
      greater than expected rise in evening peak flows for the first 2 days of
      treatment suggest the development of tolerance to the bronchodilator effect of
      terbutaline. Similarly, the fall in morning peak flows on treatment withdrawal
      suggests rebound bronchoconstriction. These effects are likely to be mediated by
      downregulation of the beta-receptor during treatment. The clinical significance
      of these changes is uncertain in view of the stability of overall asthma control
      during terbutaline treatment, but sudden withdrawal of beta-agonist treatment
      could conceivably lead to a deterioration in asthma control.

PMID- 10955753
TI  - Health-related quality of life is associated with arterial P(O2) in chronic
      obstructive pulmonary disease.
AB  - Insensitive lung-specific questionnaires may explain the poor association between
      arterial P(O2) and reported health-related quality of life. Conceivably, modern
      lung specific or generic quality of life measures might show a better association
      with arterial P(O2). Fifty-nine outpatients (34 men) with chronic obstructive
      pulmonary disease (COPD) who fulfilled the following criteria were studied: age
      18-67 years, FEV1 < or = 70%, < or = 15% reversibility after beta2-agonist
      inhalation, and no other disabling disorders. All completed the Respiratory
      Quality of Life Questionnaire (RQLQ) and Short Form 36 (SF-36), and were tested
      with spirometry and arterial blood gases. In accordance with available COPD
      staging systems, patients were divided into those with an FEV1 of < 50% and 50
      70% of predicted. Patients' characteristics were, [mean (SD)]: age: 57.0 years
      (9.0); FEV1: 1.46 (0.6). Spearman's rank correlations between arterial P(O2) and
      dimensions of the RQLQ ranged from 0.25-0.52, and were greater than for the SF-36
      (0.14-0.36) in patients with moderate to severe COPD. The association between
      arterial P(O2) and quality of life scores in moderately to severely affected COPD
      patients was moderate, but higher than previously reported. The associations were
      higher with a lung-specific questionnaire than with a general health measure,
      indicating a higher sensitivity of the lung-specific measure in this patient
      group.

PMID- 10955754
TI  - Randomized controlled trial of ambulatory oxygen and an ambulatory ventilator on
      endurance exercise in COPD.
AB  - In a prospective, randomized study we examined the effect of (i) ambulatory
      oxygen and (ii) a portable, inspiratory pressure support (IPS) device on the
      endurance shuttle walk test (ESWT) in patients with severe chronic obstructive
      pulmonary disease (COPD). Ten outpatients [median (range) FEV1 0.60 l(0.35,
      1.45)] performed the ESWT under five test conditions: baseline walk (no
      assistance), IPS at 14 cmH2O from a portable ventilator (the HIPPY, Friday
      Medical, U.K.), sham IPS (< 8 cmH2O), ambulatory oxygen at 2 l min(-1), and sham
      oxygen (carrying the portable oxygen cylinder and breathing air). There were
      significant improvements in the ESWT with ambulatory oxygen, but a negative
      effect with the HIPPY device [mean (SD) time: baseline 172 (48) sec; oxygen 242
      (62) sec; HIPPY 84 (35) sec]. The ESWT appeared sensitive to the effect of
      cylinder weight although differences in endurance capacity were not significant
      [sham oxygen 151 (45) sec]. The ESWT was sensitive to the acute application of
      oxygen, demonstrating a beneficial effect on endurance performance in patients
      with severe COPD. The ESWT could form the basis of a standardized assessment for
      ambulatory oxygen.

PMID- 10955755
TI  - Elevated levels of macrophage-stimulating protein in induced sputum of patients
      with bronchiectasis.
AB  - We recently showed that macrophage-stimulating protein (MSP), a serum protein
      homologous to hepatocyte growth factor, promotes ciliary motility by activating
      its receptor, RON, on the airway ciliated epithelium. To investigate the
      functional involvement of MSP and RON in bronchiectasis, in which mucociliary
      clearance (MCC) is impaired, first we examined RON expression on the bronchial
      ciliated epithelium of patients with bronchiectasis. We confirmed RON expression
      at the apical surface of bronchial ciliated epithelium of patients with
      bronchiectasis as well as those of normal human bronchus. Next, we examined
      whether MSP is present in sputum of patients with bronchiectasis and normal
      control subjects. By Western blotting, we found that half of the MSP in sputum is
      present as a biologically active alpha/beta chain heterodimer (mature MSP). In
      addition, we found that the MSP concentrations in sputum were significantly
      elevated in patients with bronchiectasis (n=8; 16.8+/-3.0 ng ml(-1)) compared
      with normal controls (n=9; 8.4+/-2.4 ng ml(-1); P<0.05). In contrast, the
      difference in concentrations of serum MSP (pro-MSP) was not significant between
      the two groups. These results indicate that (i) MSP is supplied to the airways
      and converted to a biologically active form, (ii) MSP is increased in patients
      with bronchiectasis compared with normal controls. Taken together, our findings
      suggest that increased MSP may be involved in compensation for impaired MCC in
      bronchiectasis.

PMID- 10955756
TI  - Interaction of Bordetella pertussis with human respiratory mucosa in vitro.
AB  - The human respiratory tract pathogen Bordetella pertussis is the major cause of
      whooping cough in infants and young children, and also causes chronic cough in
      adults. B. pertussis infection damages ciliated epithelium in the respiratory
      tract. However, the interaction of the bacterium with the respiratory mucosa is
      poorly understood, and previous studies have either utilized animal tissue which
      may not be appropriate, or isolated cell systems which lack the complexity of the
      respiratory mucosa. We have studied the interaction of B. pertussis strain BP536
      with human nasal turbinate tissue in an air-interface organ culture over 5 days.
      We have also compared infection by BP536 with two other strains, Tohama I and
      CN2992, to determine whether the interactions observed with BP536 are consistent,
      and, in both nasal turbinate and adenoid organ cultures at 24 h, to determine
      whether there were differences between tissue from different parts of the
      respiratory tract. BP536 adhered to cilia, most commonly at their base, and
      disorganized their spatial arrangement, they also adhered to damaged tissue and
      mucus, but very rarely to unciliated cells. Within the first 24 h there was a
      five-fold increase in bacterial density on ciliated cells, and the total number
      of adherent bacteria increased up to 96 h. Infection caused increased mucus at
      24h and an increase in damaged epithelium from 72 h which involved both ciliated
      and unciliated cells. The number of residual ciliated cells did not decrease
      after 72 h. The three different strains of B. pertussis exhibited similar
      interactions with the mucosa, and there was no tissue specificity for adenoid or
      turbinate tissue. We conclude that B. pertussis adhered to multiple sites on the
      mucosa and caused hypersecretion and epithelial damage which are the pathological
      changes described in vivo.

PMID- 10955757
TI  - Comparison of hydrogen peroxide generation and the content of lipid peroxidation
      products in lung cancer tissue and pulmonary parenchyma.
AB  - Lipid peroxidation, as a well-known index of reactive oxygen species activity,
      not only in lung biochemistry, is an oxidative process associated with membrane
      lipid destruction. Also, the oxidative modification of nucleic acids by reactive
      oxygen species is of remarkable biological importance as it may contribute to
      malignant conversion, but its exact role in lung cancer biology is still not
      clear. Our study aimed to investigate the level of lipid peroxidation ex vivo in
      tumour tissue and lung parenchyma obtained from patients with lung cancer. Forty
      two patients with lung cancer were enrolled into the study. During a surgical
      resection, tumour tissue and lung parenchyma were obtained and concentration of
      lipid peroxidation products, thiobarbituric acid-reactive substances and Schiff
      bases, and spontaneous generation of hydrogen peroxide, were measured. The
      concentration of thiobarbituric acid-reactive substances (P<0.001) in the tumour
      tissue was higher than that in lung parenchyma. In small cell lung cancer as well
      as in squamous cell carcinoma patients, a positive correlation between
      spontaneous generation of hydrogen peroxide in tumour tissue and clinical stage
      (r = 0.43; r = 0.46; respectively) was found. Our results prove enhanced lipid
      peroxidation in cancer tissue as compared with matched-lung parenchyma. In small
      cell lung cancer and squamous cell carcinoma patients, the high level of
      oxidative stress, expressed as a spontaneous generation of hydrogen peroxide in
      tumour tissue, was associated with clinical progression of tumour's stage.

PMID- 10955758
TI  - Increased interleukin-13 mRNA expression in bronchoalveolar lavage cells of
      atopic patients with mild asthma after repeated low-dose allergen provocations.
AB  - Immune and inflammatory responses mediated by cytokines are essential in the
      pathophysiology of asthma. The aim of this study was to analyse the cytokine mRNA
      profiles in bronchoalveolar lavage (BAL) cells of patients with mild atopic
      asthma, before and after induction of a subclinical allergic airway inflammation.
      For this purpose, eight patients with mild atopic asthma received low-dose
      allergen inhalations equivalent to 10% of a provocational dose causing a 20% fall
      in forced expiratory flow in 1 sec (PD20) for 7 weekdays. BAL was performed
      before and after low-dose provocations in patients, and without provocation in
      five healthy controls. Alveolar macrophages (AM) were enriched by negative
      selection, using magnetic beads, to enable separate studies of the BAL cells.
      Using a semiquantitative RT-PCR technique, the mRNA expression of macrophage
      derived cytokines interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-13, interferon
      (IFN)-gamma, tumour necrosis factor (TNF)-alpha and transforming growth factor
      (TGF)-beta was analysed. After low-dose provocations, we observed a significant
      increase in the expression of IL-13 mRNA (P = 0.01) in BAL cells enriched for AM
      of the asthmatic patients. The increased IL-13 mRNA positively correlated with
      the proportion of BAL fluid eosinophils (r = 0.7, P = 0.05). Moreover, a tendency
      was found towards an increased IL-1 and a reduced IL-6, IL-8, IFN-gamma and TNF
      alpha expression by the BAL cells. Comparing asthmatic patients before low-dose
      provocations and healthy controls, a significantly higher expression of IL-6
      (P<0.003), IL-10 (P<0.005) and TGF-beta (P<0.003) and a significantly lower
      expression of IL-8 (P<0.005) and TNF-alpha (P<0.01) was detected in the patients.
      In summary, repeated low-dose allergen provocations of asthmatic patients results
      in a modified BAL cell cytokine mRNA profile with increased production of IL-13,
      that may be of importance for the development of a Th2-like immune response. A
      possible source of the increased IL-13 mRNA is AM, which may have a more active
      function in the allergic inflammation than previously thought.

PMID- 10955759
TI  - Association of man-made mineral fibre exposure and sarcoidlike granulomas.
AB  - It is assumed that sarcoidosis is caused by inhalation of air borne agents in
      susceptible persons triggering the inflammatory reaction. The association of
      metallic dust exposure, such as beryllium and aluminium, and sarcoidlike
      pulmonary disorders is well known. The ability of man-made mineral fibres (MMMF)
      to cause granulomatous lung disease has not been appreciated until now. Recently,
      we observed the association of sarcoidlike granulomatous reaction and
      occupational history of glass fibre exposure. We hypothesized that there might be
      a relationship between MMMF exposure and the development of sarcoidlike
      granulomas. Therefore, the records of 50 sarcoidosis patients-who visited our
      outpatient clinic between 1996 and 1999 were reviewed. This revealed that 14
      cases recalled a history of exposure to either glass fibres or rock wool, both
      MMMF fibres. The available obtained tissue specimens (n = 12) were reviewed. In
      six cases electron microscopy qualitative analysis of small fragments of the
      tissue revealed among others silica, aluminium and sometimes titanium. A distinct
      relation between fibre deposits fibre deposits and granulomas was found. These
      findings indicate that in susceptible people MMMF exposure might be related to a
      chronic granulomatous disease similar to chronic beryllium disease.

PMID- 10955760
TI  - T-cell activation by organic dust in vitro.
AB  - Inhalation of swine dust causes intense airway inflammation with a multifold
      increase of inflammatory cells and lymphocyte activation as assessed by
      bronchoalveolar lavage. To further investigate the mechanism for lymphocyte
      activation the present in vitro study focuses on the lymphocyte response to swine
      dust in whole blood. Various concentrations of phytohaemagglutinin (PHA) (final
      concentrations: 3.16, 10.0, 3.16 and 100 microg ml(-1)) and swine dust (final
      concentrations: 10.0, 31.6, 100 and 316 microg ml(-1)) were added to heparinized
      whole blood from healthy donors. The blood samples were incubated in duplicate,
      using the homologous unstimulated blood as control, for 4, 24, 48 and 72 h in a
      water bath at 37 degrees C. The cells were stained with fluorochrome conjugated
      monoclonal antibodies. For analysis of T-cell activation CD3 was double-stained
      together with the activation markers CD69, CD25 and HLADR. Cell count percentages
      were analysed by flow cytometry. Soluble IL-2sRalpha in plasma was analysed using
      commercial sandwich ELISA technique. At baseline CD69, CD25 and HLA-DR were
      expressed in < 1%, approx 5% and < 1% of the T-cells respectively. We found a
      dose response relationship between swine dust exposure and the expression of all
      three T-cell activation markers which appeared at different time-points. Maximal
      expression of CD69 (8%, P<0.05) and CD25 (15%, P<0.001) was found after 24h of
      activation. HLA-DR was significantly expressed after 48h (8%) and maximally
      expressed after 72 h of activation (13%, P<0.05). The soluble IL-2sRalpha in
      plasma was maximally expressed after 24-48 h (1200 pg ml(1) and 1500 pg ml(-1),
      respectively. In conclusion, T-cells were activated by swine dust in vitro. Thus,
      our previous findings of T-cell activation following swine dust exposure, in vivo
      may be an effect of the dust either directly on T-cells or on other cells which
      in turn contribute to the T-cell activation.

PMID- 10955761
TI  - Is pre-menstrual asthma related to use of aspirin or non-steroidal anti
      inflammatory drugs?

PMID- 10955762
TI  - Primary pulmonary Hodgkin's disease--report of two cases.

PMID- 10955763
TI  - Design criteria for an automatic safety-alarm system for elderly.
AB  - An initiative for the design of an automatic safety-alarm system is proposed. The
      alarm system will be designed for elderly people, who are living independently
      and need some assistive care. It has to detect an emergency at home, and in that
      case, it has to send an alarm signal to an alarm centre. The detection is done
      with remote sensors. The emergencies are detected by monitoring and analysing the
      "Activities of Daily Living" (ADL) of the elderly person at home. In this
      article, the product demands are worked out and a description is given how the
      automatic safety-alarm system can be built up, and which technologies and
      components could be used.

PMID- 10955764
TI  - Transpupillary laser phototherapy of tumors and vascular anomalies of retina and
      choroid: theoretical approach and clinical implications.
AB  - BACKGROUND: Small retinal and choroidal tumors situated near the optic nerve or
      macula, such as retinoblastomas and malignant melanomas, as well as various other
      anomalies, in particular vascular malformations, may successfully be treated by
      photocoagulation. Model assumptions geared towards maximizing efficiency and
      minimizing undesirable side effects are forwarded, and the most important
      parameters subserving photothermal destruction, such as radiation field and
      thermal energy, analyzed. The influence exerted by physical traits of various
      tissues involved are also considered. METHODS: The model approximations presented
      are based on classical radiation and absorption laws, as well as on the
      scattering properties of the various tissues implicated, these being considered
      as a function of wavelength and their relevance to the photodestructive task at
      hand. Particular attention is paid to the rate processes and reaction kinetics of
      irradiated proteins. CONCLUSIONS: Radiation sources emitting in the near-infrared
      range of the electromagnetic spectrum, such as the diode (810 nm) and the cw
      Nd:YAG (1064 nm) lasers, are optimal for the treatment of tumors and large,
      voluminous entities (such as Hippel-Lindau angiomas), owing to the good tissue
      penetration properties of their light. Those emitting in the shorter wavelength
      range, such as the argon ion (488 and 514 nm) and first harmonic--mode Nd:YAG
      (532 nm) lasers, are not suitable for such tasks, but they are ideal for the
      destruction of fine sanguinous structures, within which their light is strongly
      absorbed but through which it penetrates poorly. For the treatment of large
      anomalous structures, a combined short/long wavelength--strategy should also be
      considered as a viable alternative. Such a "wavelength mixture" is emitted by the
      xenon high pressure lamp of the once renowned Meyer-Schwickerath light
      coagulator. The precision and safety of photothermal destruction methods depend,
      in the first approximation, upon the details of the pulse energy deposition
      (wavelength, pulse height and duration, pulse dynamics, mode composition,
      focussing), the choice of which is determined by the optical and thermal
      constants of the irradiated tissues. Higher pulse energies will, of course, be
      more effective in destroying neoplastic cells, but the risk of producing
      undesired collateral heat damage will also increase concomitantly. Until we can
      ascertain the physical properties of the pathological tissues treated with
      certainty, we will hardly be able to achieve more than an approximation of an
      ideal treatment strategy. But with increasing developments in in vivo-diagnostic
      techniques, we expect that this goal will be attainable in the not too distant
      future.

PMID- 10955765
TI  - Virtual reality as telemedicine tool: technology, ergonomics and actual
      applications.
AB  - This paper surveys the state of the art in telemedicine applications of virtual
      environments (VEs) and related technologies for health care. The possible use of
      VEs as telemedicine tool has attracted much interest in medicine. Actually this
      technology is commonly used in remote or augmented surgery, and surgical
      training, which are critically dependent upon eye-hand coordination. Recently,
      however, different researchers have tried to use VEs in anatomic learning and for
      the assessment and rehabilitation in neuro-psychology. To date, such applications
      have improved the quality of health care, and later they will lead to substantial
      cost savings. Tools that respond to the needs of present VE systems are being
      refined or developed. However, the possible use of VEs in telemedicine is not
      linked to the solution of technical problems only. In fact telemedicine is not
      simply a technology but a complex process whose successful exploitation needs
      significant attention to ergonomics, human factors and organizational changes in
      the structure of the relevant health service.

PMID- 10955766
TI  - Flexural stress waves responses on human femoral cortical bone.
AB  - The response of human femoral cortical bone to lateral impact were investigated
      both analytically and experimentally. In the analytical part of this
      investigation the Timoshenko beam theory was used for predicting the propagation
      of flexural stress waves along the specimens. The final solution was given in
      integral form and the results were obtained with the aid of a digital computer.
      In the experimental part of this investigation the employed specimens were
      obtained by cutting a human femur shaft along its length and the specimens were
      machined to have a uniform rectangular cross-section. Flexural stress waves in
      cortical bone were generated by impacting transversely 4.8 mm diameter spherical
      projectiles, fired from an air gun with the appropriate velocities. Stress waves
      were detected at two stations (positions) on the beam specimens by means of foil
      strain gages. These gages were suitably connected with a digital storage
      oscilloscope to detect the flexural stress waves produced by the lateral impact.
      Force history was recorded also on a storage oscilloscope by means of a
      sandwiched quartz crystal arrangement, of high frequency response, placed at the
      impact point of the specimen. A comparison was made between the corresponding
      analytical results and experimental data. Significant agreement was observed
      between them, as shown in the figures of this article.

PMID- 10955767
TI  - Vertebral stress of a cervical spine model under dynamic load.
AB  - The objective of this study is to develop cervical spine models that predict the
      stresses in each vertebra by taking account of the biodynamic characteristics of
      the neck. The loads and the moments at the head point (Occipital Condyle) used
      for the models were determined by the rigid body dynamic response of the head due
      to G-z acceleration. The experimental data used were collected from the
      biodynamic responses of human volunteers during an acceleration in the z
      direction on the drop tower facility at Armstrong Laboratory at Wright Patterson
      Air Force Base (WPAFB). Three finite element models were developed: an elastic
      local model, viscoelastic local model and complete viscoelastic model. I-DEAS
      software was used to create the solid models, the loadings and the boundary
      conditions. Then, ABAQUS finite element software was employed to solve the
      models, and thus the stresses on each vertebral level were determined. Beam
      elements with different properties were employed to simulate the ligaments,
      articular facets and muscles. The complete viscoelastic model was subjected to 11
      cases of loadings ranging from 8 G-z to 20 G-z accelerations. The von Mises and
      Maximum Principal stress fields, which are good indicators of bone failure, were
      calculated for all the cases. The results indicated that the maximum stress in
      all cases increased as the magnitude of the acceleration increased. The stresses
      in the 10 to 12 G-z cases were comfortably below the injury threshold level. The
      majority of the maximum stresses occurred in C6 and C4 regions.

PMID- 10955768
TI  - 2D and 3D dose distribution determination in proton beam radiotherapy with
      GafChromic film detectors.
AB  - This paper presents the results obtained using radiochromic (MD-55 GafChromic)
      film for the 2D and 3D dosimetric reconstruction of the dose delivered by a
      proton beam under the real conditions of a programme of radiotherapy treatment
      for ocular tumours. Standard microdensitometric measurements were used to
      determine the variation in film optical density (O.D.) vs dose. Calibration
      curves were obtained by least-square fitting of the experimental OD values using
      a second order polynomial. This allows conversion of O.D. to dose. With this
      procedure it was possible to determine the distribution of the dose delivered by
      the proton beam in a phantom composed of layers of GafChromic film, with high
      surface spatial resolution and, through sections, the complete mapping of the
      dose delivered to a volume subjected to irradiation, as in a course of
      radiotherapy treatment.

PMID- 10955769
TI  - Aerosolized delivery and lung cancer prevention: pre-clinical models show
      promise.

PMID- 10955770
TI  - Clinical use of tyrosine kinase inhibitors: therapy for chronic myelogenous
      leukemia and other cancers.

PMID- 10955771
TI  - Can O6-alkylguanine-DNA alkyltransferase depletion enhance alkylator activity in
      the clinic?

PMID- 10955772
TI  - Progression model for pancreatic cancer.

PMID- 10955773
TI  - N-(4-hydroxyphenyl)retinamide in the chemoprevention of squamous metaplasia and
      dysplasia of the bronchial epithelium.
AB  - Lung cancer remains the number one cause of cancer-related deaths in the United
      States. To reduce the mortality associated with this disease, individuals at risk
      must be identified prior to the development of lung cancer, and effective
      prevention strategies must be developed. One such strategy is to use retinoids
      like N-(4-hydroxyphenyl)retinamide (4-HPR), which has been found to possess
      chemopreventive activities in preclinical studies. In this study, 139 smokers
      were registered and 82 were randomized onto a double-blinded, placebo-controlled
      chemoprevention trial of 4-HPR administered p.o. (200 mg once daily). Of these,
      70 participants were eligible for response evaluation. Biopsies were obtained at
      six predetermined sites in the bronchial tree from participants before and at the
      completion of 6 months of treatment. 4-HPR treatment had no measurable effect on
      histopathology (squamous metaplasia and dysplasia) in the bronchial epithelium of
      current smokers. 4-HPR was detected (104.5+/-64.0 ng/ml, mean +/- SD) in the
      serum of participants, supporting its potential bioavailability. Serum retinol
      levels decreased markedly (44% of placebo-treated patients) as a consequence of 4
      HPR treatment. Notably, the mRNA level of retinoic acid receptor beta, which is
      typically increased by retinoid treatment, did not change in the bronchial
      epithelium of 4-HPR-treated participants. Clonal populations of bronchial
      epithelial cells were detected by analysis of loss of heterozygosity at putative
      tumor suppressor loci on chromosomes 3p, 9p, and 17p, and these changes were not
      altered by 4-HPR treatment. In conclusion, at this dose and schedule, 4-HPR was
      not effective in reversing squamous metaplasia, dysplasia, or genetic and
      phenotypic abnormalities in the bronchial epithelium of smokers.

PMID- 10955774
TI  - Telomerase activity and Bcl-2 expression in non-small cell lung cancer.
AB  - Bcl-2 and p53 are the most relevant proteins in apoptosis and tumor development.
      Telomerase functions in the maintenance of telomeres and is indispensable for
      immortalization. Bcl-2 was reported as a direct modulator of telomerase activity,
      and a correlation between p53 and telomerase activity was reported. The aim of
      this study was to determine the relationships between Bcl-2, p53, and telomerase
      activity in non-small cell lung cancer. Immunostaining for Bcl-2, p53, and Ki-67
      was performed in 64 surgically resected non-small cell lung cancers, and a
      fluorescence-based telomeric repeat amplification protocol assay for
      semiquantitative analysis of telomerase activity was done. Twenty-eight (44%) and
      33 (52%) cases showed positive staining for Bcl-2 and p53, respectively. Bcl-2
      expression was associated with negative lymph node involvement (P = 0.0248). p53
      expression was associated with tumor size (P = 0.0244), p stage (P = 0.0391), and
      proliferative activity (P = 0.0004). Telomerase activity was detected in 89.1%
      and was closely associated with aggressive clinicopathological features.
      Telomerase activity was higher in p53-positive tumors (P < 0.0001), but
      represented no correlation with Bcl-2 expression (P = 0.3239). Interestingly,
      when the cases were stratified by histological grade and the level of Ki-67
      labeling index, Bcl-2 expression was more clearly associated with favorable
      clinicopathological features and lower telomerase activity only in low-grade
      tumors. In conclusion, p53 is closely associated with telomerase activity. In low
      grade tumors, Bcl-2 is inversely correlated to telomerase activity. Our results
      suggest that the biological role of the Bcl-2 protein alters according to tumor
      aggressiveness, thereby cofunctioning with telomerase against genetic
      instability.

PMID- 10955775
TI  - C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary
      lung cancers.
AB  - Previous studies have shown that the expression of the cell-cell adhesion
      molecule (C-CAM1), located at chromosome 19, is down-regulated in several types
      of human cancers, including prostate and breast cancers. Two major isoforms of C
      CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, are derived from
      the C-CAM1 gene through alternative splicing. Tumor cells transfected with L-form
      C-CAM1, which contains a cytoplasmic domain, display significantly lower growth
      rates and less tumorigenicity in both in vitro and in vivo models compared with
      untransfected tumor cells, suggesting that L-form C-CAM1 may be a tumor
      suppressor. The transfection of the cytoplasmic domain of L-form C-CAM1 could
      also cause suppression of tumor growth, further supporting the role of L-form C
      CAM1 in tumorigenesis. In contrast to reports of most of the tumor types tested,
      Ohwada et al. (Am. J. Respir. Cell Mol. Biol., 11: 214-220, 1994) reported that C
      CAM1 was not down-regulated or even up-regulated in lung cancer. Because the
      cytoplasmic domain of L-form C-CAM1 is critical for the tumor suppressor function
      of C-CAM1, we hypothesized that switching of the isoform rather than down-
      regulation of C-CAM1 gene expression occurs during lung tumorigenesis. To test
      this hypothesis, we analyzed pairs of tumor tissue and corresponding normal
      appearing lung tissue from 51 patients with non-small cell lung cancer (NSCLC)
      and 43 cell lines to determine expression profiles of L-form C-CAM1 and S-form C
      CAM1 using reverse transcription-PCR. We found that L-form C-CAM1 was the
      predominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most
      (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantly S
      form C-CAM1 (P < 0.0001). Similarly, 19 (79%) of the 24 NSCLC cell lines and 17
      (85%) of the 20 small cell lung cancer cell lines expressed predominantly S-form
      C-CAM1. The frequent alteration of the C-CAM1 expression pattern suggests that C
      CAM1 has an important role in lung tumorigenesis.

PMID- 10955776
TI  - Risk of gastric cancer in hereditary nonpolyposis colorectal cancer in Korea.
AB  - After endometrial cancer, gastric cancer is the second most common extracolonic
      cancer in cases of hereditary nonpolyposis colorectal cancer (HNPCC), where the
      relative risk in HNPCC familial members is known to be 4-fold. However, it is not
      yet clear whether HNPCC families from Korea, an endemic area for gastric cancer,
      have the same relative risk or whether the incidence of gastric cancer is high
      enough to justify familial screening. To clarify these questions, we investigated
      1011 individuals from 66 Korean HNPCC families (28 families fulfilled the
      Amsterdam criteria and 38 did not). The overall and age-specific relative risk of
      gastric cancer in HNPCC families when compared with the background population was
      calculated. Twenty-five patients with gastric cancer were identified from among
      22 HNPCC families. The calculated risk of gastric cancer in patients with HNPCC
      and their first-degree relatives was 2.1-fold greater than in the general
      population (95% confidence interval; range, 1.4-3.2). However, the relative risk
      of gastric cancer in the younger generations was much greater (11.3-fold in the
      30s and 5.5-fold in the 40s). Additionally, the relative risk was greater in
      mutation carrier families than noncarrier families (3.2-fold versus 1.6-fold).
      This study demonstrates that the risk of gastric cancer in members of HNPCC
      families in a gastric cancer endemic population, particularly in younger subjects
      and mutation carrier families, is high enough to justify careful screening.

PMID- 10955777
TI  - Racial disparity in the frequency of PTEN mutations, but not microsatellite
      instability, in advanced endometrial cancers.
AB  - Survival of African Americans with endometrial cancer is significantly worse than
      that of whites. Mutation of the PTEN tumor suppressor gene and microsatellite
      instability occur in some endometrial cancers, and they are associated with
      favorable prognostic features. The aim of this study was to determine whether
      there is a racial disparity in the frequency of these molecular alterations that
      contributes to differences in outcome in advanced endometrial cancer. We screened
      140 stage III/IV endometrial adenocarcinomas (78 Caucasian, 62 African American)
      for mutations in the PTEN gene. Paired DNA samples were available in 100 cases
      and were analyzed for microsatellite instability using three polymorphic markers.
      African-American women had cancers with significantly higher stage and grade that
      were more often nonendometrioid. In addition, median survival of African
      Americans (1.0 years) was worse than that of whites (2.5 years; P = 0.02). PTEN
      mutation was seen in 20 of 140 (14%) cancers and was associated with endometrioid
      histology and more favorable survival. The frequency of PTEN mutations was
      significantly higher in whites (17 of 78; 22%) than in African Americans (3 of
      62; 5%; P = 0.006). Microsatellite instability was found in 15% of cancers,
      exclusively in endometrioid cases, and was associated with favorable survival (P
      = 0.01). There was no racial difference in the frequency of microsatellite
      instability. We conclude that mutation of the PTEN tumor suppressor gene is
      associated with favorable survival in advanced endometrial cancer and is 4-fold
      more frequent in Caucasians relative to African Americans. This suggests that
      differences in the frequency of PTEN mutations contribute to the racial disparity
      in endometrial cancer survival.

PMID- 10955778
TI  - Synergistic antitumor effect of chemotherapy and antisense-mediated ablation of
      the cell cycle inhibitor p27KIP-1.
AB  - The fraction of noncycling cells found in most tumors represents a major obstacle
      for conventional chemotherapy. Here, we show that the cyclin-dependent kinase
      inhibitor p27KIP-1 accumulates to high levels in human tumors grown in
      immunodeficient mice. We have developed an antisense phosphorothioate
      oligodeoxynucleotide (ODN) that efficiently inhibits the expression of p27KIP-1
      both in vitro and in vivo. Treatment of cultured tumor cells with this ODN
      sensitized the cells to all chemotherapeutic drugs tested, including the new
      kinase inhibitor flavopiridol. Furthermore, striking synergistic effects of the
      p27KIP-1 ODN and flavopiridol were observed in vivo with respect to both the
      induction of apoptotic cell death and the inhibition of tumor growth.
      Importantly, p27KIP-1 ODN treatment alone did not provoke any detectable tumor
      enhancement. A mechanistic explanation for these findings might be derived from
      the observation that p27 ODN treatment of cultured tumor cells led to a clear
      increase in the fraction of S-G2 cells in the absence of an efficient progression
      into M phase. These findings may have direct relevance to the development of new
      approaches for the treatment of human cancer.

PMID- 10955779
TI  - Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer
      chemopreventive agent in A/J mice at low doses: a pilot study.
AB  - In previously treated head-and-neck cancer patients, p.o. administered
      isotretinoin (13-cis retinoic acid) reduced the occurrence of second
      aerodigestive tumors, including lung tumors, but side effects made chronic
      therapy problematic. We reasoned that inhaled isotretinoin might provide
      sufficient drug to the target cells for efficacy while avoiding systemic
      toxicity, and we proceeded with the pilot study reported here. Male A/J mice were
      given single i.p. doses of urethane, a common experimental lung carcinogen, or
      benzo[a]pyrene (BaP) or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK),
      putative major carcinogens in tobacco smoke. The following day, exposures to
      isotretinoin aerosols for 45 min daily at 1.3, 20.7, or 481 microg/l were
      initiated. After 2 weeks, the high dose caused severe toxicity on the snout skin,
      necessitating a reduction of dose frequency to twice a week. As a precaution, the
      mid dose was reduced to three exposures per week. The weekly total deposited
      doses after the dose frequency reductions were calculated to be 0.24, 1.6, and
      24.9 mg/kg for the low, mid, and high doses, of which 16% was estimated to be
      deposited in the lungs. The weekly deposited pulmonary drug doses were calculated
      to be 0.01, 0.07, and 1.1% of a previously reported ineffective oral dose in
      urethane-treated A/J mice. After 10-16 weeks, mice were sacrificed to count areas
      of pulmonary hyperplasia and adenomas. For all carcinogens, the mice exposed to
      the high isotretinoin dose showed reductions of tumor multiplicity ranging from
      56 to 80% (P < 0.005). The mid dose was associated with reductions of tumor
      multiplicity by 67 and 88% (P < 0.005) in BaP- and NNK-treated mice,
      respectively, and was tolerated until approximately 12 weeks, when both these and
      the high-dose mice began losing weight. The low-dose mice had nonsignificant
      reductions of 30% (P < 0.13) and 16% (P < 0.30) for BaP- and NNK-treated mice,
      respectively without any evidence of side effects. For BaP- and NNK-treated mice,
      numbers of hyperplastic areas directly correlated to dose level and inversely to
      tumor number, suggesting arrested progression. Inhaled mid-dose isotretinoin
      caused up-regulation of lung tissue nuclear retinoic acid receptors (RARs)
      relative to vehicle-exposed mice, RARalpha (3.9-fold vehicle), RARbeta (3.3
      fold), and RARgamma (3.7-fold), suggesting that these receptors may be useful
      biomarkers of retinoid activity in this system. The encouraging results from this
      pilot study suggest that inhaled isotretinoin merits evaluation in people at high
      risk for lung cancer.

PMID- 10955780
TI  - Phase I clinical and pharmacological study of O6-benzylguanine followed by
      carmustine in patients with advanced cancer.
AB  - O6-benzylguanine (BG) is a potent inactivator of the DNA repair protein O6
      alkylguanine-DNA alkyltransferase (AGT) that enhances sensitivity to nitrosoureas
      in tumor cell lines and tumor-bearing animals. The major objectives of this study
      were to define the optimal modulatory dose and associated toxicities of
      benzylguanine administered alone and in combination with carmustine; to define
      the maximally tolerated dose and associated toxicities of carmustine administered
      with benzylguanine and to describe the pharmacokinetics of BG in humans and its
      effects on AGT depletion and recovery in peripheral blood mononuclear cells.
      Patients with histologically confirmed advanced solid tumors or lymphoma that had
      failed to respond to standard therapy or for which no standard therapy was
      available were eligible to participate in this study. Patients initially received
      BG as a 1-h i.v. infusion without carmustine. After a 14-day washout (ie.,
      without therapy) period, patients received BG as a 1-h i.v. infusion followed, 1
      h later, by a 15-min i.v. infusion of carmustine. Cycles of chemotherapy were
      repeated every 6 weeks. Cohorts of patients received BG doses ranging from 10 to
      120 mg/m2 and carmustine doses ranging from 13 to 50 mg/m2. Plasma and urine
      samples were collected and analyzed for BG, and O6-benzyl-8-oxoguanine
      concentrations and AGT activity was determined in peripheral blood mononuclear
      cells. There was no toxicity attributable to BG alone at any dose tested. Bone
      marrow suppression was the primary and dose-limiting toxicity of BG combined with
      carmustine and was cumulative in some patients. The neutrophil nadir occurred at
      a median of day 27, with complete recovery in most patients by day 43.
      Nonhematological toxicity included fatigue, anorexia, increased bilirubin, and
      transaminase elevation. Recommended doses for Phase II testing are 120 mg/m2 BG
      given with carmustine at 40 mg/m2. BG rapidly disappeared from plasma and was
      converted to a major metabolite, O6-benzyl-8-oxoguanine, which has a 2.4-fold
      higher maximal concentration and 20-fold higher area under the concentration
      versus time curve than BG. AGT activity in peripheral blood mononuclear cells was
      rapidly and completely suppressed at all of the BG doses. The rate of AGT
      regeneration was more rapid for patients treated with the lowest dose of BG but
      was similar for BG doses ranging from 20-120 mg/m2. In conclusion,
      coadministration of BG and carmustine is feasible in cancer patients, but the
      maximal dose of carmustine that can be safely administered with BG is
      approximately one-third of the standard clinical dose. Bone marrow suppression,
      which may be cumulative, is the dose-limiting toxicity of the combination.
      Prolonged AGT suppression is likely attributable primarily to the effect of O6
      benzyl-8-oxoguanine.

PMID- 10955781
TI  - Comparative pharmacokinetic analysis of 5-fluorouracil and its major metabolite 5
      fluoro-5,6-dihydrouracil after conventional and reduced test dose in cancer
      patients.
AB  - The aim of this study was to investigate the clinical pharmacokinetics of 5
      fluorouracil (5-FU) and its major metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU)
      in 20 colorectal cancer patients given two dose levels of 5-FU, 250 and 370
      mg/m2, administered by i.v. bolus. A reverse-phase high-performance liquid
      chromatographic method was used for the simultaneous assay of 5-FU and 5-FDHU in
      plasma samples obtained at baseline and at multiple time points from 5 min to 4 h
      after 5-FU bolus as well as to assess the activity of dihydropyrimidine
      dehydrogenase (DPD) in peripheral blood mononuclear cells (PBMCs) before 5-FU
      dosing. Plasma pharmacokinetic parameters of patients given 250 mg/m2 5-FU were
      significantly different from those receiving 370 mg/m2; main differences were
      observed in the trapezoidal areas under the plasma levels-versus-time curve from
      to to the last measurable concentration (area under the curve, 3.77+/-0.21 versus
      13.61+/-2.3 h x microg/ml), peak plasma concentration (Cmax, 18.15+/-1.35 versus
      48.41+/-7.69 microg/ml), and total body clearance (CL(TB), 54.64+/-3.54 versus
      25.43+/-2.3 l/h/m2). Significant differences were also observed in the main
      pharmacokinetic parameters of 5-FDHU after 250 and 370 mg/m2 5-FU including the
      area under the curve from to to 4 h (5.39+/-0.32 versus 8.75+/-1.24 h x
      microg/ml), Cmax (3.60+/-0.16 versus 5.26+/-0.55 microg/ml) and time to Cmax
      (Tmax, 0.45+/-0.03 versus 0.69+/-0.06 h). The mean DPD activity in PBMCs in this
      group of patients was 205.7+/-36.4 pmol of 5-FDHU/min/mg of protein and was
      within the normal range; however, no significant correlations were found between
      5-FU or 5-FDHU pharmacokinetic parameters at two dose levels and DPD activity of
      PBMCs. The results of the present study provide the first detailed comparison of
      the distribution of 5-FU and its major metabolite 5-FDHU at the therapeutic level
      as well as at reduced test dose levels to obtain pharmacokinetic data to be used
      as reference values for the identification of patients at risk of major 5-FU
      toxicity due to impaired metabolism to 5-FDHU.

PMID- 10955782
TI  - Marked 24-h rest/activity rhythms are associated with better quality of life,
      better response, and longer survival in patients with metastatic colorectal
      cancer and good performance status.
AB  - The rest/activity circadian cycle has been used as a reference for chemotherapy
      administration at specific times to improve tolerability and efficacy. Because
      cancer processes may be associated with alterations of circadian rhythms, the
      rest/activity cycle was monitored noninvasively to assess its relationship with
      tumor response, survival, and quality of life in 200 patients with metastatic
      colorectal cancer. Patients wore an actigraph, a wristwatch that records the
      number of accelerations per minute, for 3 days before receiving chronomodulated
      chemotherapy. The circadian rhythms in activity were estimated by two robust
      parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy
      index (I<O) for comparing amounts of activity when in bed and out of bed.
      Accurate data for inclusion, quality of life, response, and survival were
      available for 192 patients. Survival at 2 years was 5-fold higher (P = 10(-4)) in
      patients with marked activity rhythm (I<O in upper quartile) than in those with
      rhythm alteration (I<O in lower quartile). These results were supported by the
      multivariate Cox analysis. Multivariate regression analysis showed that circadian
      rhythms in activity (I<O; P = 3 x 10(-4)) and in WBCs (P = 0.03) as well as
      performance status (P = 0.02) were jointly prognostic of response. Patients with
      marked rest/activity rhythms also had better quality of life and reported
      significantly less fatigue. The individual rest/activity cycle provides a novel
      independent prognostic factor for cancer patients' survival and tumor response as
      well as a quantitative indicator for quality of life.

PMID- 10955783
TI  - Safety and biodistribution of 99mTechnetium-labeled anti-CD44v6 monoclonal
      antibody BIWA 1 in head and neck cancer patients.
AB  - The CD44 protein family consists of isoforms, encoded by standard exons and up to
      nine alternatively spliced variant exons (v2-v10), which are expressed in a
      tissue-specific way. Expression of v6-containing variants (CD44v6) has been
      related to aggressive behavior of various tumor types and was shown to be
      particularly high in squamous cell carcinoma (SCC). Therefore, CD44v6 might be a
      suitable target for radioimmunoscintigraphy (RIS) and therapy. The present study
      evaluates the novel high-affinity murine anti-CD44v6 monoclonal antibody (MAb)
      BIWA 1 for its safety and targeting potential in patients with SCC of the head
      and neck (HNSCC). Twelve HNSCC patients, who had planned to undergo resection of
      the primary tumor and neck dissection, were included. Preoperatively, 2, 12, or
      52 mg of 99nTc-labeled MAb BIWA 1 was administered. RIS results obtained 21 h
      after injection were compared with palpation, computed tomography, and magnetic
      resonance imaging, with histopathology as the gold standard. Moreover,
      biodistribution of BIWA 1 was evaluated by radioactivity measurement in blood and
      bone marrow and in biopsies from the surgical specimen obtained 40 h after
      injection. The distribution of BIWA 1 in tumor biopsies was analyzed by
      immunohistochemistry. BIWA 1 integrity in the blood was assessed by high
      performance liquid chromatography and related to soluble CD44v6 levels in serum
      samples. No drug-related adverse events were observed. Human antimouse antibody
      responses were observed in 11 patients. The diagnostic efficacy of RIS appeared
      to be comparable for the three BIWA 1 dose levels and for the four diagnostic
      methods. Besides activity uptake in tumor tissue, minimal accumulation of
      activity was observed in mouth, lungs, spleen, kidney, bone marrow, and scrotal
      area. Analysis of tissue biopsies revealed high uptake in tumors, with a mean
      value of 14.2+/-8.4% of the injected dose/kg tumor tissue and a mean tumor:blood
      ratio of 2.0+/-1.4 at 40 h after injection. Differences among the three dose
      groups were not statistically significant, although a trend toward lower uptake
      in the highest dose group was noted. Distribution of BIWA 1 throughout the tumor
      was heterogeneous for all dose groups, which might be related to the high
      affinity of the MAb. The mean biological half-life in blood (34.5+/-6.1 h) was
      not dose dependent. Extensive complex formation of BIWA 1 was observed in the 2
      mg group, most probably with soluble CD44v6 present in the blood, and complex
      formation relatively diminished upon increase of the MAb dose. BIWA 1 is a
      promising MAb for targeting HNSCC because it can be safely administered to HNSCC
      patients, while it shows high and selective tumor uptake. However, BIWA 1 is
      immunogenic, and therefore a chimerized or humanized derivative of BIWA 1 with
      intermediate affinity will be used in future clinical trials.

PMID- 10955784
TI  - Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal
      antibody to the integrin alphavbeta3.
AB  - Angiogenesis plays a central role in the growth and metastasis of cancers.
      Strategies aimed at interfering with tumor blood supply offer promise for new
      cancer therapies. Vitaxin (an anti-alphavbeta3 antibody) interferes with blood
      vessel formation by inducing apoptosis in newly generated endothelial cells. This
      Phase I study evaluates the safety and pharmacokinetics of Vitaxin in humans with
      cancer. Eligible patients demonstrated progressive tumors with stage IV disease
      and an Eastern Cooperative Oncology Group performance status < or =2. Treatment
      consisted of six weekly infusions of Vitaxin. Escalating doses from 0.1 and 4.0
      mg/kg/week were evaluated based on the expectation that plasma levels would
      bracket the effective in vitro concentration. Escalation beyond 4 mg/kg/week was
      limited by drug availability. Adverse events were assessed weekly.
      Pharmacokinetics were performed weekly through week 9. Clinical response was
      assessed at week 9. Of 17 patients treated, 14 were evaluable for response.
      Treatment was well tolerated with little or no toxicity. The most common side
      effect was infusion-related fever, which could be controlled with prophylactic
      antipyretics. Doses > or =1 mg/kg/week produced plasma concentrations sufficient
      to saturate the alphavbeta3 receptor in vitro (25 microg/ml). Vitaxin
      demonstrated a half-life in excess of 5 days at higher doses with no accumulation
      over 6 weeks of therapy. One patient demonstrated a partial response, and seven
      patients demonstrated stable disease. Three patients received Vitaxin beyond the
      first cycle of therapy. Each of these patients demonstrated disease stabilization
      that in one case lasted 22 months. At the doses and schedule studied, Vitaxin
      appears safe and potentially active, suggesting that vascular integrin
      alphavbeta3 represents a clinically relevant antiangiogenic target for prolonged
      cancer therapy.

PMID- 10955785
TI  - A phase I-II study of isolated hepatic perfusion using melphalan with or without
      tumor necrosis factor for patients with ocular melanoma metastatic to liver.
AB  - There are no satisfactory treatment options for patients with ocular melanoma
      metastatic to liver, and after liver metastases are identified, median survival
      is only between 2 and 7 months. Because liver metastases are the sole or life
      limiting component of disease in the vast majority of patients who recur, we
      reasoned that complete vascular isolation and perfusion of the liver might result
      in clinically meaningful regression of disease. Between September 1994 and July
      1999, 22 patients (13 women and 9 men; mean age, 49 years) with ocular melanoma
      metastatic to liver were treated with a 60-min hyperthermic isolated hepatic
      perfusion (IHP) using melphalan alone (1.5-2.5 mg/kg, n = 11) or with tumor
      necrosis factor (TNF, 1.0 mg, n = 11). Via a laparotomy, IHP inflow was via the
      hepatic artery alone (n = 17) or hepatic artery and portal vein (n = 5) and
      outflow from an isolated segment of inferior vena cava. Most patients had
      advanced tumor burden with a mean percentage of hepatic replacement of 25%
      (range, 10-75%) and a median number of metastatic nodules of 25 (range, 5 to
      >50). Complete vascular isolation was confirmed in all patients using a
      continuous intraoperative leak monitoring technique with 131I radiolabeled
      albumin. There was one treatment mortality (5%). The overall response rate in 21
      patients was 62% including 2 radiographic complete responses (9.5%) and 11
      partial responses (52%). The overall median duration of response was 9 months
      (range, 5-50) and was significantly longer in those treated with TNF than without
      (14 versus 6 months, respectively; P = 0.04). Overall median survival in 22
      patients was 11 months. These data indicate that a single 60-min IHP can result
      in significant regression of advanced hepatic metastases from ocular melanoma.
      TNF appears to significantly prolong the duration of response.

PMID- 10955787
TI  - A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody
      encoding adenovirus (AD21): a phase I trial.
AB  - The purpose of this Phase I study was to determine the feasibility of using an
      anti-erbB-2-encoding adenovirus (Ad21) to treat erbB-2-overexpressing ovarian
      cancer. Recurrent ovarian cancer patients were treated i.p. with Ad21 in dosages
      ranging from 1 x 10(9) to 1 x 10(11) pfu. Patients were monitored after treatment
      for evidence of clinical toxicity and efficacy. Peritoneal aspirates and serum
      samples were obtained to assess for evidence of gene transfer/expression, for
      generation of wild-type vector, and antiadenoviral humoral response. Fifteen
      patients were treated per study specifications. Treatment-specific grade 1/2
      fever was experienced by 9 of 15 (60%) patients. Other transient grade 1/2
      constitutional, pain, and gastrointestinal symptoms were also experienced. No
      dose-limiting vector-related toxicity was experienced. Of 13 patients evaluable
      for response, 5 (38%) had stable disease and 8 (61%) had evidence of progressive
      disease. One patient with nonmeasurable disease normalized her CA125 at the 8
      week evaluation, and one patient with nonmeasurable disease remained without
      clinical evidence of disease for 6 months after treatment. PCR analysis of
      peritoneal aspirates demonstrated the presence of Ad21 in 84.6%, 84.6%, and 61.6%
      of evaluable specimens at days 2, 14, and 56 after treatment, respectively. No
      wild-type virus was detected. Reverse transcription-PCR analysis demonstrated
      expression of the anti-erbB-2 sFv-encoding gene in 10 of 14 evaluable patients at
      day 2. Five of six evaluable patients had an increase in antiadenovirus antibody
      titer. This study suggests that adenoviral-mediated gene therapy using an anti
      erbB-2-directed intrabody is feasible in the context of human ovarian cancer.

PMID- 10955786
TI  - Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with
      refractory solid malignancies.
AB  - Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and antitumor
      activity in murine tumor models. Putative mechanisms of action include activation
      of the transforming growth factor beta pathway and/or inhibition of p21ras
      signaling, leading to differentiation or apoptosis. In this Phase I trial, 17
      patients took POH p.o. three times daily for 14 days of each 28-day cycle. The
      starting dose of POH was 1600 mg/m2/dose, with escalations to 2100 and 2800
      mg/m2/dose in subsequent cohorts. Chronic nausea and fatigue were dose-limiting
      toxic effects at 2800 mg/m2. Grade 1-2 hypokalemia was common at 2100 and 2800
      mg/m2. Although POH could not be detected in plasma, two of its metabolites,
      dihydroperillic acid (DHPA) and perillic acid (PA), were measured in plasma and
      urine on days 1 and 15 after the first and last doses of POH, respectively. Both
      area under the concentration versus time curve and peak plasma concentration
      (Cmax) values increased with dose and exhibited high intersubject variability.
      Day 15 DHPA Cmax values ranged from a mean +/- SD of 22.6+/-12 microM at 1600
      mg/m2/dose to 42.4+/-15.24 microM at 2800 mg/m2/dose. Corresponding mean +/- SD
      Cmax values for PA were 433.2+/-245.8 and 774.1+/-439.6 microM. One patient
      treated at the 2800 mg/m2/dose had markedly prolonged plasma levels of both PA
      and DHPA and developed grade 3 mucositis. POH treatment did not consistently
      alter the expression of p21ras, rap1, or rhoA in peripheral blood mononuclear
      cells obtained from patients treated at the highest dose level. The metabolites
      PA and DHPA did not change expression or isoprenylation of p21ras in MCF-7 breast
      or DU145 prostate carcinoma cells at concentrations that exceeded those achieved
      in patient plasma after POH treatment. We conclude that POH at 1600-2100 mg/m2
      p.o. three times daily is well tolerated on a 14-day on/14-day off dosing
      schedule. Inhibition of p21ras function in humans is not likely to occur after
      POH administration at safe doses of the present oral formulation.

PMID- 10955788
TI  - Phase I pharmacokinetic study of the novel antitumor agent SR233377.
AB  - SR233377 is a novel thioxanthenone analogue that demonstrated solid tumor
      selectivity in vitro with activity confirmed in vivo against several murine
      tumors including those of colon, pancreas, and mammary origin. Its primary
      preclinical dose-limiting toxicities included myelosuppression and neurological
      toxicity. The neurological toxicity was acute and could be ameliorated in mice
      when the drug was administered as a 1-h infusion instead of rapid i.v. injection.
      As a result of its preclinical efficacy profile, SR233377 entered Phase I
      clinical investigation. The compound was administered i.v. over 2 h on day 1
      repeated every 28 days. The starting dose was 33 mg/m2 (one-tenth the mouse
      LD10). Escalations continued to 445 mg/m2 (six escalations), where dose-limiting
      toxicity was observed. At this dose, acute ventricular arrhythmias, including one
      patient with torsades de pointes and transient cardiac arrest, occurred. Because
      this toxicity might have been related to the plasma peak, the protocol was
      amended to a 24-h infusion beginning at 225 mg/m2. With this dose, prolongation
      of the corrected QT interval (QTc) over the pretreatment levels resulted. Because
      prolonged QTc is a known forerunner to acute ventricular arrhythmias, clinical
      development of SR233377 was stopped. However, preclinical antitumor and toxicity
      studies with analogues are underway with hopes of identifying a new clinical
      candidate with similar antitumor effects that is devoid of cardiac toxic effects.

PMID- 10955789
TI  - High-dose therapy with 90Yttrium-labeled monoclonal antibody CC49: a phase I
      trial.
AB  - A Phase I trial of increasing administered activities of 90yttrium (90Y)-labeled
      monoclonal antibody (MAb) CC49 was conducted to determine whether
      extrahematopoietic toxicity occurred with this radioimmunoconjugate. Twelve
      patients with various gastrointestinal tract cancers were administered a tracer
      dose of 111In-labeled MAb CC49 for biodistribution and pharmacokinetic studies.
      Patients then underwent a single treatment with increasing administered
      activities of 90Y-labeled MAb CC49 (0.3, 0.4, and 0.5 mCi/kg). Biodistribution
      studies, using 111In-labeled MAb CC49 as a surrogate, were determined using
      planar and single photon emission computed tomography imaging. Pharmacokinetic
      studies were performed by measuring radioactivity in blood samples taken at
      intervals after radioimmunoconjugate infusions. Tissue biopsies of tumor
      metastases and related normal tissues (liver and bone marrow) were obtained for
      radioactivity measurements. Radiation dosimetry estimates were calculated using
      these data. Toxicity was evaluated using the National Cancer Institute Common
      Toxicity Criteria. No dose limiting extrahematopoietic toxicity was identified in
      the range of administered activities used in this study. Radioimmunolocalization
      based on planar and single photon emission computed tomography images 111In
      labeled MAb CC49 showed heterogeneous (nonspecific) liver and splenic uptake.
      Liver metastases were usually photopenic, and extrahepatic metastases showed
      faint to moderate uptake. The alpha and beta half-lives of 111In-labeled MAb CC49
      and 90Y-labeled MAb CC49 in the blood were similar. Absorbed radiation dose
      estimates in metastatic tumor sites ranged from 180 to 3000 cGy. The percentage
      of injected dose/kg of tumor ranged from 1.12 to 18.14; however, tumor:normal
      liver ratios were consistently <1. No objective responses were observed. Doses of
      up to 0.5 mCi/kg could be administered with reversible grade IV myelotoxicity.
      Absorbed radiation dose in tumor was suboptimal, even at the highest administered
      activity level. Deposition of 90Y in liver was high, and estimates of absorbed
      dose in liver equaled or exceeded that which could be achieved in metastatic
      tumor sites. Strategies to enhance access of radioimmunoconjugates in tumor and
      diminish deposition in the liver need to be developed for effective treatment
      using MAb CC49 with chelated radiometals.

PMID- 10955791
TI  - Prognostic value of bone marrow angiogenesis in multiple myeloma.
AB  - We studied the prognostic value of angiogenesis grading and microvessel density
      estimation in newly diagnosed multiple myeloma. Seventy-five patients with newly
      diagnosed myeloma, treated on Eastern Cooperative Oncology Protocol E9486 and
      Intergroup study 0141 (S9321) at the Mayo Clinic, were studied. Bone marrow
      microvessels were examined using immunohistochemical staining for von Willebrand
      factor. Determination of microvessel density and angiogenesis grading was done in
      a blinded manner. There was a strong correlation between microvessel density and
      the plasma cell labeling index, rho 0.42, P < 0.001. Angiogenesis grade was also
      significantly associated with the plasma cell labeling index. Fifteen % of
      patients with low-grade angiogenesis had a high labeling index (>1%). In
      contrast, 47% of patients with intermediate or high-grade angiogenesis had high
      labeling indices (P = 0.02). Overall survival was significantly different among
      those with high-, intermediate-, and low-grade angiogenesis, with median times of
      2, 4, and 4.4 years, respectively (P = 0.02). Similarly, patients with
      microvessel density >50/x400 field had poorer survival compared with those with
      50 or fewer microvessels/field, median survival 2.6 versus 5.1 years,
      respectively (P = 0.004). There was a strong association between angiogenesis
      grade and microvessel density (P < 0.001). We conclude that bone marrow
      angiogenesis is a predictor of poor survival in newly diagnosed myeloma.
      Angiogenesis is correlated with the plasma cell labeling index but not the bone
      marrow plasma cell percentage. A simple visual grading of angiogenesis is an
      efficient alternative to microvessel density estimation.

PMID- 10955790
TI  - Predictive value of p53, mdm-2, p21, and mib-1 for chemotherapy response in
      advanced breast cancer.
AB  - p53 is a transcription factor that participates in cell cycle checkpoint
      processes and apoptosis. The protein product of the murine double minute gene 2
      (mdm-2) plays a central role in the regulation of p53. In response to DNA
      damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21)
      is an important downstream effector in the p53-specific growth arrest pathway. In
      breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21
      expression provides information on how patients will respond to chemotherapy. Mib
      1 monoclonal antibody recognizes the proliferation-related antigen Ki-67. High
      tumor proliferation has previously been associated with response to chemotherapy.
      p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical
      methods in primary tumors derived from 134 patients who took part in a randomized
      multicenter trial comparing docetaxel to sequential methotrexate and 5
      fluorouracil (MF) in advanced breast cancer. Low mib-1 staining correlated with
      negative p53 staining (P = 0.001), and mdm-2 and p21 stainings correlated
      positively with each other (P < 0.001). p53, mdm-2, p21, and mib-1 expression
      were not significantly associated with response to chemotherapy, time to
      progression, or overall survival in the whole patient population or in the
      docetaxel group. However, in the MF group, a low mib expression (<25%) and a high
      mdm-2 expression (> or =10%) predicted a better response (P = 0.014 and P =
      0.046, respectively) to treatment and a longer time to progression in both
      univariate and multivariate analyses. p53 staining status was not associated with
      response to treatment in either group. Interestingly, tumors with both negative
      mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to
      docetaxel but no response to MF. Although highly preliminary, the findings
      suggest that different tumor biological factors may predict response to different
      chemotherapy regimens with distinct mechanisms of action. The results of our
      phenotype analysis also indicate that it is more likely that a panel of tumor
      biological factors instead of only one single factor may be needed for better
      prediction of chemotherapy response.

PMID- 10955792
TI  - Detection of MUC1-expressing mammary carcinoma cells in the peripheral blood of
      breast cancer patients by real-time polymerase chain reaction.
AB  - We have prospectively analyzed blood samples of 122 patients with breast disease
      for the presence of circulating expressing MUC1 cells before and after treatment.
      Among them, 28 patients had histologically confirmed benign breast disease (group
      1), 34 patients had operable breast cancer (group 2), and 60 patients had
      advanced breast cancer (group 3). Circulating epithelial cells were isolated with
      BerEP4-coated immunomagnetic beads. Total RNA was extracted and reverse
      transcribed before analysis by real-time PCR of a MUC1-specific cDNA sequence.
      The sensitivity of the reverse transcription-PCR tested with blood spiked with
      MCF7 cells was one cell in 5 ml of blood. The immunomagnetic separation step was
      mandatory to obtain the maximum specificity. Control samples from healthy donors
      never displayed cycle threshold (Ct) values for MUC1 lower than 38. Circulating
      cells (Ct, <38) were detected in 3 of 28 (11%) cases in group 1, in 8 of 34 (24%)
      cases in group 2, and in 27 of 60 cases (45%) in group 3. A semiquantitative
      estimate of blood-borne cells could be derived from the Ct value when below 32
      (the lowest was 28) or by the number of positive aliquots of the same blood
      sample. Thus, immunomagnetic separation, followed by MUC1-specific RT-PCR, allows
      the semiquantitative detection of circulating mammary cells. A significant
      correlation between the presence of MUC1-positive cells and the group of breast
      tumors was observed. The clinical significance of blood-borne cells in breast
      cancer, especially at the operable stage, may be investigated by following these
      patients.

PMID- 10955793
TI  - Residual bone marrow leukemic progenitor cell burden after induction chemotherapy
      in pediatric patients with acute lymphoblastic leukemia.
AB  - We used highly sensitive multiparameter flow cytometry and blast colony assays to
      quantify the leukemic progenitor cell (LPC) burden of postinduction chemotherapy
      bone marrows from newly diagnosed and relapsed pediatric patients with acute
      lymphoblastic leukemia (ALL). Of 890 newly diagnosed patients, 243 (27%) had
      detectable LPC in the postinduction bone marrow samples with an average (mean +/-
      SE) LPC content of 22+/-9 LPC/10(6) mononuclear cell (MNC; range, 0-7199/10(6)
      MNC; median, 0/10(6) MNC). By comparison, 24 of 50 (48%) patients with relapsed
      ALL had detectable LPC in their postinduction bone marrow specimens (P = 0.003),
      and their average LPC content was 202+/-139 LPC/10(6) MNC. Fewer patients with B
      lineage ALL (170 of 786; 22%) than patients with T-lineage ALL (73 of 104; 70%)
      harbored residual LPC in their postinduction bone marrow specimens (P < 0.0001).
      This correlation with immunophenotype was independent of the National Cancer
      Institute risk classification. Similarly, 19 of 44 (43%) patients with relapsed B
      lineage ALL versus 5 of 6 (83%) patients with relapsed T-lineage ALL harbored
      residual LPC in their postinduction bone marrow specimens (P = 0.09). Among newly
      diagnosed patients, those with high-risk ALL seemed to have larger numbers of
      residual LPC in their bone marrow after induction chemotherapy than those with
      standard risk ALL (53+/-26, n = 286 versus 7+/-1, n = 604, P = 0.04). LPC of
      patients with standard risk ALL who had a slow early marrow response at day 7
      seemed to be more resistant to the three-drug induction chemotherapy than
      patients who had a rapid early marrow response. Overall, the order of
      chemosensitivity of LPC was: newly diagnosed standard risk B-lineage > newly
      diagnosed higher risk B-lineage > newly diagnosed standard risk T-lineage > newly
      diagnosed higher risk T-lineage > relapsed B-lineage > relapsed T-lineage.
      Notably, LPC- patients whose end-of-induction remission bone marrow specimens had
      zero LPC had an excellent early event-free survival outcome. Within the standard
      and high-risk subsets, LPC- patients had a 2.6-fold lower and 2.4-fold lower
      incidence of events, respectively, than LPC+ patients. At 6 months, 12 months, as
      well as 24 months, the ranking order for better event-free survival was: standard
      risk, LPC- > high risk, LPC- > standard risk, LPC+ > high risk, and LPC+.

PMID- 10955794
TI  - Loss of p21Waf1 expression is a strong predictor of reduced survival in primary
      superficial bladder cancers.
AB  - p21Waf1 is a downstream effector of p53 and belongs to the Cip1/Kip1 family of
      cyclin-dependent kinase inhibitors. Thus, it is a potential tumor suppressor gene
      and likely plays an important role in tumor development. Moreover, reduced
      expression of p21Waf1 has been reported to have prognostic value in several human
      malignancies. In this study, we evaluated the prognostic value of p21Waf1 in
      bladder cancer compared with other clinicopathological features and with p27Kip1
      and p53 expression. A total of 96 superficial (pTa-1) human bladder carcinomas
      were immunohistochemically stained for p21Waf1 protein expression. Positive
      p21Waf1 staining (> or =5% positive nuclei) was observed in 68 of the 96 (71%)
      tumors. p21Waf1 expression was neither associated with tumor stage (P = 0.9) nor
      with tumor grade (P = 0.18) but was significantly associated with both p53
      protein expression (> or =20% positive nuclei; P = 0.007) and with p53 gene
      mutations (P = 0.017). A significant correlation was also observed between
      positivity for p21Waf1 and high (>50% positive cells) p27Kip1 expression (P =
      0.04). With regard to prognosis, patients whose tumors showed absence of p21Waf1
      staining displayed a significantly shorter overall survival (P = 0.01 by log-rank
      test). However, p21Waf1 expression did not correlate with disease-free survival
      (P = 0.15 by log-rank test). On a multivariate analysis that also included p53
      and p27Kip1 expression, negative p21Waf1 staining was an independent predictor of
      reduced overall survival (P = 0.004; relative risk, 5.32), stronger than age and
      tumor stage. These data indicate that expression of p21Waf1 protein strongly
      correlates with survival and might represent a useful prognostic marker in
      primary superficial bladder carcinomas.

PMID- 10955795
TI  - Different vulnerability among chromosomes to numerical instability in gastric
      carcinogenesis: stage-dependent analysis by FISH with the use of microwave
      irradiation.
AB  - Numerical chromosomal abnormalities are a well known characteristic of human
      cancer, but no "chromosome-wide investigation" encompassing almost all of the
      chromosomes has ever been reported. Furthermore, although the multistep process
      of carcinogenesis is widely accepted in human cancer, the stepwise numerical
      aberration of chromosomes has never been addressed. Touch preparations of 24
      (male 20, female 4) surgically resected gastric cancer tissue samples in various
      stages in terms of depth of invasion were analyzed by fluorescence in situ
      hybridization using centromere-specific probes including 17 chromosomes, 1-4, 6
      8, 10-12, 15-18, 20, X, and Y. Microwave irradiation was performed to increase
      the sensitivity and specificity of the signal. The depth of the tumor invasion in
      the gastric wall and histological subtypes were recorded by viewing the histology
      of the adjacent portion. Numerical chromosomal abnormalities of chromosomes 1 and
      2 were found most frequently and from the early stage of gastric cancer. The
      abnormalities observed were limited to chromosomes 1, 2, 4, and 20 in tumors
      invading to the middle layer of the submucosa of the gastric wall, but these
      became more extensive, involving almost all of the chromosomes investigated when
      the tumor had invaded beyond the proper muscle of the gastric wall. Centromeric
      numbers of chromosomes 3 and 18 were exceptionally stable even after the tumor
      progressed to advanced stage. These profiles of the sequential process of
      numerical chromosomal abnormality were similar in both mucocellular and tubular
      type gastric cancer, but the prevalence was significantly lower in the
      mucocellular type (39.0% versus 68.0%). On the basis of fluorescence in situ
      hybridization analysis of 17 different chromosome centromeres in gastric cancer
      in various stages, we conclude that the earliest events in gastric carcinogenesis
      in terms of chromosomal abnormality occur in chromosomes 1 and 2 and that
      chromosomal numerical aberrations expand in a stepwise manner with cancer
      progression.

PMID- 10955796
TI  - Correlation of plasma and serum vascular endothelial growth factor levels with
      platelet count in colorectal cancer: clinical evidence of platelet scavenging?
AB  - Most studies measuring circulating vascular endothelial growth factor (VEGF) have
      sampled serum rather than plasma. There has been much debate whether the
      collection of sera (which causes the activation of platelets and VEGF release) is
      a true reflection of tumor angiogenic activity or whether platelets act as
      scavengers of VEGF. Addressing this issue, we measured serum and plasma VEGF,
      before and after colorectal resection, with reference to platelet counts. Serum
      and plasma samples were collected from 116 colorectal cancer (CRC) and 116
      control patients. Ninety CRC and 32 benign resections were performed. Both plasma
      and serum VEGF were significantly higher in CRC patients (18.5 and 327 pg/ml,
      respectively) compared with controls (9.0 and 151.5 pg/ml, respectively; P <
      0.0001). Paired serum and plasma VEGF measurements correlated in both CRC (r =
      0.56) and control patients (r = 0.73; P < 0.0001). Serum and plasma VEGF levels
      correlated with platelet count in CRC patients (r = 0.58 and 0.44, respectively)
      but not in controls. Plasma and serum VEGF levels, and VEGF concentration per
      platelet, increased with advancing disease stage. The correlation of serum and
      plasma VEGF with platelet counts in CRC but not in benign disease may be
      attributable to the scavenging of VEGF from the tumor source by platelets, with
      plasma levels reflecting free circulating VEGF in equilibrium with platelet
      levels. VEGF levels in citrated plasma are low and lie close to the limits of
      ELISA sensitivity. We recommend that a standardized measurement of serum VEGF-
      normalized by the patient's platelet count to give a value of serum VEGF per
      platelet--be adopted.

PMID- 10955797
TI  - P53 mutational status improves estimation of prognosis in patients with
      curatively resected adenocarcinoma in Barrett's esophagus.
AB  - The incidence of adenocarcinomas in Barrett's esophagus has been rising in the
      last two decades in the United States and Western Europe for yet unknown reasons.
      We reported previously a large multi-institutional trial implicating p53
      mutations as being involved in the pathogenesis of Barrett's cancer and
      representing an early marker for the malignant potential of Barrett's epithelium.
      A prospective study was performed to evaluate the prognostic impact of p53
      mutations on survival in 59 patients with Barrett's cancer. Tissue for DNA
      analysis was obtained by endoscopic biopsy or immediately after surgical
      resections from the tumor, Barrett's epithelium, and normal stomach and
      esophagus. p53 mutation analysis was performed by PCR-single strand
      conformational polymorphism screening of exons 5-9 and DNA sequencing to
      unequivocally prove the presence of a mutation. p53 mutations were identified in
      30 of 59 (50.8%) patients. The presence of a p53 mutation in the tumor had a
      significant impact on survival after curative resections (RO-resections) with
      cumulative 5-year survival probabilities of 68.8+/-9.7% for mutation-negative
      tumors and 24.3+/-9.9% for mutation-positive tumors (log rank: P < 0.001). By Cox
      proportional hazard analysis, including the parameters of gender, age, Union
      International Contre Cancer tumor stage, grading, and p53 mutation status, only
      Union International Contre Cancer tumor stage (P < 0.0001) and p53 mutation
      status (P < 0.02) were of significant independent prognostic importance. p53
      mutation analysis by DNA sequencing is of significant independent prognostic
      importance next to histopathological tumor stage in patients with curatively
      resected (RO-resection) Barrett's cancer. It appears that p53 mutational status
      is a valuable parameter to define low-risk (p53 mutation-negative) and high-risk
      (p53 mutation-positive) groups for treatment failure after curative resections.

PMID- 10955798
TI  - Potential role of microvessel density in predicting radiosensitivity of T1 and T2
      stage laryngeal squamous cell carcinoma treated with radiotherapy.
AB  - Curative radiotherapy is the first choice of therapy for T1 and T2 stage
      laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation.
      Patients with recurrent tumors who undergo salvage surgery require prolonged
      nasal feeding. Therefore, clinical interest has been focused on elucidating a
      predictive factor indicating which tumors are likely to be radiosensitive before
      radiotherapy. We analyzed the relations between radiosensitivity and
      clinicopathological factors (gender, tumor location, histological factors, and
      clinical tumor-node-metastasis stage), expression of apoptosis-related proteins
      (p53, bax, bcl-2), apoptotic index using the terminal deoxynucleotidyltransferase
      mediated nick end labeling method, expression of cell proliferation-related
      proteins (Ki-67-labeling index and epidermal growth factor receptor
      overexpression) and microvessel density (MVD, vessels/field = 0.391 mm2) in
      biopsy specimens from 31 LSCC patients given radiotherapy (total radiotherapy
      dose of 52-70 Gy over 4-6.5 weeks). Univariate analysis revealed that tumors with
      a high MVD (> or =35 vessels/field) showed better radiosensitivity than those
      with a low MVD (<35 vessels/field, P = 0.008) and that a high Ki-67-labeling
      index (> or =40%) was weakly associated with radiosensitivity (P = 0.056).
      Multivariate analysis and Kaplan-Meier analysis showed that MVD alone had
      significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after
      radiotherapy (P = 0.012, 0.0003, respectively). No significant association
      between clinicopathological factors, or of overexpression of p53, bax, bcl-2,
      epidermal growth factor receptor, or apoptotic index, with radiosensitivity was
      found. These results indicate that MVD is a potentially useful clinical factor
      predicting radiosensitivity for patients with early stage LSCCs before treatment.

PMID- 10955799
TI  - Detection of circulating cancer cells by reverse transcription-polymerase chain
      reaction for uroplakin II in peripheral blood of patients with urothelial cancer.
AB  - Few attempts have been made at the molecular detection of urothelial cancer cells
      in the blood or lymph nodes mainly because of an absence of good candidate
      molecular or genetic changes specific to urothelial cancer or urothelium. In
      1990, however, genes that encode urothelium-specific transmembrane proteins,
      uroplakins (UPs), were cloned. We have established a method of detecting
      circulating cancer cells in peripheral blood of patients with transitional cell
      carcinoma by nested reverse transcription-PCR assay for UP II. UP II mRNA
      positive cells were detected in 3 (10.3%) of 29 patients with superficial cancers
      (pTa-1N0M0), 4 (28.6%) of 14 patients with muscularly invasive cancers (pT2
      4N0M0), 2 (40.0%) of 5 loco-regional node-positive patients (pN1-2M0), and 6
      (75.0%) of 8 patients with distant metastases. Positive rates, therefore,
      increased with tumor extension (P = 0.0033, Kruskal-Wallis test). Furthermore,
      sequential blood sampling was performed in three patients with metastases during
      and after systemic chemotherapy, and UP-II-positive cells were found to have
      disappeared in two patients who responded well to the systemic chemotherapy.
      These results suggest that our nested reverse transcription-PCR assay for UP II
      is highly specific and might be used as a tumor marker for molecular staging of
      urothelial cancers, although the sensitivity is not so optimal.

PMID- 10955800
TI  - Loss of imprinting and genetic alterations of the cyclin-dependent kinase
      inhibitor p57KIP2 gene in head and neck squamous cell carcinoma.
AB  - The p57KIP2 is a maternally expressed and paternally imprinted cyclin-dependent
      kinase inhibitor located on chromosome 11p15.5. Because of its location,
      biochemical functions, and imprinting status, p57KIP2 has been considered a
      candidate tumor suppressor gene. To determine, for the first time, the
      involvement of this gene in the development of head and neck squamous carcinoma
      (HNSC), we analyzed the imprinting and expression status and loss of
      heterozygosity (LOH) within the p57KIP2 gene flanking loci on the 11p15.5 region
      in 64 primary untreated tumors. Of the 30 (47%) informative cases for this gene,
      loss of imprinting and LOH were noted in 4 (13%) and 10 tumors (33%),
      respectively. Analysis of the microsatellite markers flanking the p57KIP2 gene on
      chromosome 11p showed infrequent alterations at these loci. p57KIP2 was expressed
      in all tumors with LOH within and around the gene. Quantitative reverse
      transcription-PCR analysis showed elevated p57 mRNA expression in tumor with loss
      of imprinting. Sequencing analysis of exons 1 and 2 of the p57KIP gene failed to
      detect any mutations. Our data indicate: (a) infrequent genomic abnormalities at
      the p57KIP2 gene in HNSC; (b) leaky or incomplete imprinting of the paternal
      allele is associated with increased expression of this gene in a subset of
      tumors; and (c) minimal evidence for suppressor function for this gene in HNSC.

PMID- 10955801
TI  - EMS1 gene amplification correlates with poor prognosis in squamous cell
      carcinomas of the head and neck.
AB  - The relationship between CCND1 and/or EMS1 amplification and disease outcome was
      studied in a prospective series of 104 head and neck squamous cell carcinomas
      treated by surgical resection. The CCND1 and EMS1 copy number in tumor samples
      was estimated by differential PCR. The presence or absence of amplification was
      analyzed in relation to clinicopathological variables, tumor recurrence, and
      patient survival. CCND1 amplification occurred in 32 cases (31%) and was
      associated with increased lymph node stage (P = 0.005) and advanced disease stage
      (P = 0.003). EMS1 amplification was identified in 21 cases (20%) and was related
      with advanced T stages (P = 0.001), increased lymph node stage (P = 0.02),
      advanced disease stage (P = 0.041), poor histological differentiation (P =
      0.018), recurrent disease (P = 0.0004), and reduced disease-specific survival (P
      < 0.0001). Coamplification of both genes occurred in 11 cases (11.5%).
      Multivariate analysis confirmed that in addition to regional lymph node status,
      EMS1 amplification is an independent predictor of death from the tumor (P =
      0.0027). CCND1 amplification was not prognostic. These data indicate that EMS1
      amplification, but not CCND1 amplification, predicts early recurrence and reduced
      survival in squamous cell carcinoma of the head and neck. The prognostic
      significance previously attributed to CCND1 amplification may be attributable to
      its frequent coamplification with EMS1.

PMID- 10955802
TI  - Superoxide dismutases in gastric and esophageal cancer and the prognostic impact
      in gastric cancer.
AB  - The oxidant-antioxidant balance is thought to be important in the initiation,
      promotion, and therapy resistance of cancer. In the present study, we assessed
      the expression of the antioxidants manganese superoxide dismutase (Mn-SOD) and
      copper/zinc superoxide dismutase in gastric and esophageal carcinomas and their
      relation with clinical outcome. Adenocarcinomas of the stomach (n = 81) as well
      as squamous cell carcinomas of the esophagus (n = 10) showed an enhanced
      immunohistochemical expression of Mn-SOD, which was accompanied by a
      significantly higher tissue level (P < or = 0.007) compared with their
      corresponding normal mucosa. In contrast, copper/zinc superoxide dismutase was
      found to be marginally lower in these malignant tissues in comparison with the
      normal tissues. The superoxide dismutase levels were not found to be associated
      with major clinicopathological features of the gastric cancer patients.
      Univariate analysis revealed, however, that a high Mn-SOD level in gastric
      carcinomas, a low level in the normal gastric mucosa, and a high ratio of these
      two levels in gastric cancer patients are indicative of a poor overall survival.
      Multivariate analysis, including all clinicopathological parameters, revealed
      that the Mn-SOD ratio in particular is an independent prognostic parameter in
      gastric cancer patients.

PMID- 10955803
TI  - Allelic loss at 1p34-36 predicts poor prognosis in node-negative breast cancer.
AB  - Allelic losses of specific chromosomal regions in the DNA of tumor cells, which
      imply loss of tumor suppressor genes normally resident at those loci, may become
      useful postoperative prognostic indicators for breast cancers that have not yet
      metastasized to lymph nodes. To examine whether specific allelic losses might
      correlate with postoperative disease-free survival, we tested tumors from a
      cohort of 228 node-negative breast cancer patients for allelic losses at 18
      microsatellite loci chosen to represent either a known tumor suppressor gene or a
      region where genetic alterations are frequent in breast tumors. We followed the
      patients clinically for 5 years or until death (if patient death occurred before
      completion of 5 years of follow-up). Patients whose tumors had lost an allele at
      1p34-36 bore significantly higher risks of postoperative recurrence than those
      whose tumors retained both alleles of the markers in that region [the 5-year
      recurrence rate was 15% among patients with losses versus 2% among patients with
      retention (P = 0.001)]. Multivariate analysis demonstrated that allelic loss at
      1p34-36 was an independent postoperative predictor of shorter disease-free
      survival (hazard ratio, 5.8; P = 0.0117). Thus, allelic losses at 1p34-36 in a
      tumor might have a potential to serve as a negative prognostic indicator to guide
      postoperative management of breast cancer patients, especially in the selection
      of high-risk women who will benefit from adjuvant chemotherapy and endocrine
      therapy.

PMID- 10955804
TI  - Enhanced expression of N-myc messenger RNA in neuroblastomas found by mass
      screening.
AB  - A substantial fraction of neuroblastomas found by mass screening have been
      suggested to regress spontaneously because of the high incidence of infantile
      neuroblastomas in the screening population. In this study, 70 neuroblastomas were
      analyzed for expression of proto-oncogenes related to neuronal differentiation to
      clarify the biological significance of proto-oncogene expression in the screening
      positive and -negative tumors. The tumors consisted of 39 neuroblastomas found by
      screening (group 1), 16 non-N-myc-amplified neuroblastomas found by clinical
      symptom(s) (group 2), and 15 N-myc-amplified neuroblastomas found by clinical
      symptom(s) (group 3). The expression of c-src, trk A, and N-myc in tumor tissues
      was analyzed by quantitative RNA PCR. Neuronal c-srcN2 expression varied
      significantly in the following order: group 1 > group 2 > group 3. The level of
      expression of trk A was markedly reduced in group 3 but did not differ in groups
      1 and 2. Most tumors in group 3 overexpressed N-myc. However, N-myc expression in
      group 1 was significantly higher than that in group 2. Thus, the characteristics
      of proto-oncogene expression in screening-positive tumors included enhanced
      expression of c-srcN2 and N-myc mRNA, regardless of nonamplification of N-myc.
      Our results suggest that the role of N-myc differs in neuroblastomas detected by
      screening and in N-myc-amplified tumors.

PMID- 10955805
TI  - P-glycoprotein and multidrug resistance protein activities in relation to
      treatment outcome in acute myeloid leukemia.
AB  - Despite treatment with intensive chemotherapy, a considerable number of patients
      with acute myeloid leukemia (AML) die from their disease due to the occurrence of
      resistance. Overexpression of the transporter proteins P-glycoprotein (P-gp) and
      multidrug resistance protein (MRP) 1 has been identified as a major cause of
      cross-resistance to functionally and structurally unrelated drugs. In the present
      study, the functional activity of P-gp and MRP was determined in 104 de novo AML
      patients with a flow cytometric assay using rhodamine 123 (Rh123) in combination
      with PSC833 and carboxyfluorescein (CF) in combination with MK-571. The results
      were compared with clinical outcome and with known prognostic factors. The
      functional activity of P-gp and MRP, expressed as Rh123 efflux blocking by PSC833
      and CF efflux blocking by MK-571, demonstrated a great variability in the AML
      patients. A strong negative correlation was observed between Rh123 efflux
      blocking by PSC833 and Rh123 accumulation (r(s) = -0.69, P < 0.001) and between
      CF efflux blocking by MK-571 and CF accumulation (r(s) = -0.59, P < 0.001). A low
      Rh123 accumulation and a high Rh123 efflux blocking by PSC833 were associated
      with a low complete remission (CR) rate after the first cycle of chemotherapy (P
      = 0.008 and P = 0.01, respectively). Patients with both low Rh123 and CF
      accumulation (n = 16) had the lowest CR rate (6%), whereas patients with both
      high Rh123 and CF accumulation (n = 11) had a CR rate of 73%. AML patients with
      French-American-British classification M1 or M2 showed a lower Rh123 accumulation
      than patients with French-American-British classification M4 or M5 (P = 0.02). No
      association was observed between the multidrug resistance parameters and overall
      survival of the AML patients. Risk group was the only predictive parameter for
      overall survival (P = 0.003).

PMID- 10955806
TI  - Alteration of DNA ploidy status and cell proliferation induced by preoperative
      radiotherapy is a prognostic factor in rectal cancer.
AB  - To identify predictors of prognosis after preoperative radiotherapy, DNA ploidy
      and cell proliferation were investigated in 116 patients with rectal cancer. For
      flow cytometry, a nuclear suspension was prepared by pepsin digestion of paraffin
      samples of biopsies taken before preoperative radiotherapy (15 x 2 Gy) and also
      of the resected rectal tumors after radiotherapy. The median follow-up period was
      6 years. The proportion of tumor necrosis was evaluated in histological sections
      before and after irradiation. There was a significant decrease (74 to 48%) in
      aneuploid tumors after radiation. Of 86 patients with aneuploid biopsies, 28
      revealed no reduction in the proportion of aneuploid tumor cells [group
      AN(=/increase)], and 58 showed a reduction (mean 48.9%) or complete elimination
      of aneuploid tumor cells [group AN(decrease/psi)]. The incidence of local or
      distal failure was significantly reduced in the group AN(decrease/psi)
      (7.8%/20%), compared with the group AN (=/increase) (27%/54%) and the group of
      constant diploid tumors (n = 22; 13.6%/31.8 %; P = 0.034). There was a trend of
      decreased recurrence rate in diploid tumors with a reduced fraction of cells in S
      phase after radiotherapy. Survival was significantly increased in group
      AN(decrease/psi) (P < 0.0001). In a multivariate regression analysis, variables
      of independent prognostic significance were increased proportion of necrosis
      after irradiation and DNA ploidy group and the postoperative tumor stage. These
      results suggest that alterations in tumor DNA ploidy and cell proliferation
      induced by preoperative radiotherapy might help to identify patients likely to
      benefit from preoperative radiation in rectal cancer.

PMID- 10955807
TI  - 11q23 allelic loss is associated with regional lymph node metastasis in melanoma.
AB  - Genetic alterations of the long arm of chromosome 11 have been implicated in
      melanoma pathogenesis, and we recently identified two distinct regions of common
      allelic loss in chromosomal band 11q23. To establish the point in time of
      melanoma tumorigenesis at which these two putative tumor suppressor loci become
      relevant, we investigated allelic loss [loss of heterozygosity (LOH)] in both
      chromosomal regions in tumors of progressing patients. We analyzed 102 tumor
      samples from 23 patients for whom at least two (10 patients) or three (13
      patients) tumor samples from different clinical progression steps (such as
      primary tumor and/or in-transit metastasis and/or regional lymph node metastasis
      and/or distant metastasis) were available. We detected no 11q23 LOH at any stage
      in 3 of 23 patients and detected LOH at all stages tested in 8 of 23 patients. In
      8 of the remaining 12 (67%) patients with 11q23 LOH at some stage during tumor
      progression, we found this to occur first at regional lymph node metastasis. Two
      of these patients retained constitutional heterozygosity in several in-transit
      metastases that developed up to 7 months after lymph node metastases that already
      had loss. We therefore conclude that 11q23 LOH is associated with regional lymph
      node metastasis in melanoma. Finally, we detected an allele shift restricted to a
      histomorphologically distinct part of a primary melanoma and found that the same
      parental chromosome was affected by allelic loss in a subsequently occurring
      lymph node metastasis. These findings support our conclusion and give additional
      evidence for the hypothesis of molecular heterogeneity of early tumor cell
      populations in melanoma.

PMID- 10955808
TI  - Somatic mutation of PTEN in vulvar cancer.
AB  - PTEN, a candidate tumor suppressor gene located at chromosome 10q23.3, has been
      shown to be mutated in approximately 40% of endometrial cancers. Such mutations
      have also been identified in endometrial hyperplasia, indicating that
      inactivation of the PTEN tumor suppressor gene is an early event in the genesis
      of some endometrial cancers. In this study, we have extended the analysis of PTEN
      in gynecological cancer to include adenocarcinoma of the cervix and vulvar
      carcinomas. Microdissected tissue (including normal tissues), preneoplastic, and
      neoplastic lesions were analyzed from 9 patients with cervical cancer and 10
      patients with vulvar cancer. Only 1 cervical adenocarcinoma displayed a PTEN
      mutation. In contrast, five of eight vulvar carcinomas studied harbored PTEN
      mutations. Alterations were identified in carcinoma in situ as well as squamous
      cell carcinoma of the vulva. In two patients, PTEN mutations were identified in
      mucosal regions with mild or focal dysplasia. These results suggest that PTEN is
      frequently altered in vulvar carcinomas and can be found associated with early
      dysplastic changes in vulvar mucosa.

PMID- 10955809
TI  - Angiostatin expression in non-small cell lung cancer.
AB  - Angiostatin, a potent inhibitor of angiogenesis, tumor growth, and metastasis,
      was examined in a panel of human lung cancer cell lines with Western blot
      analysis and in 143 primary non-small cell lung carcinomas with
      immunohistochemistry. Thirty-four of 143 cases (24%) stained positively. Patients
      with angiostatin-positive tumors survived longer (146 weeks) than patients with
      angiostatin-negative tumors (77 weeks; log-rank test: P = 0.07; rank-sum test: P
      = 0.02). To determine whether combining stimulating and inhibiting factors might
      improve the prognostic capability, both angiostatin and vascular endothelial
      growth factor (VEGF) were analyzed together with respect to patient survival. The
      median survival time of patients with angiostatin-positive/VEGF-negative
      carcinomas was 184 weeks, whereas the median survival time of patients with
      angiostatin-negative/VEGF-positive tumors was only 52 weeks. The angiostatin
      positive tumors exhibited an increased incidence of apoptosis and a reduced
      capability to be transplanted into nude mice, but these differences did not reach
      or were only of borderline statistical significance.

PMID- 10955810
TI  - Peroxisome proliferator-activated receptor alpha is an androgen-responsive gene
      in human prostate and is highly expressed in prostatic adenocarcinoma.
AB  - Peroxisome proliferator-activated receptor (PPAR) alpha is a member of the
      nuclear receptor superfamily of ligand-activated transcription factors. PPARalpha
      is activated by peroxisome proliferators and fatty acids and has been shown to be
      involved in the transcriptional regulation of genes involved in fatty acid
      metabolism. In rodents, the PPARalpha-mediated change in such genes results in
      peroxisome proliferation and can lead to the induction of hepatocarcinogenesis.
      Using the mRNA differential display technique and Northern blot analysis, we have
      shown that chronic exposure of the prostate cancer epithelial cell line LNCaP to
      the synthetic androgen mibolerone results in the down-regulation of PPARalpha
      mRNA. Levels of PPARalpha mRNA are reduced to approximately 40% of control levels
      in LNCaP cells exposed to 10 nM mibolerone for 96 h. PPARalpha-responsive
      reporter plasmids derived from human ApoA-II and muscle carnitine palmitoyl
      transferase I genes were stimulated by the PPARalpha-activating ligand Wy-14,643
      in LNCaP cells. In situ hybridization and immunohistochemical analyses showed
      that PPARalpha expression in prostate is confined to epithelial cells. In benign
      prostatic tissue, PPARalpha mRNA was either absent or only weakly expressed in
      the basal epithelial cells. In 11 of 18 (61%) poorly differentiated (Gleason
      score, 8-10) prostatic carcinoma specimens, there was strong expression of
      PPARalpha compared with 4 of 12 Gleason score 7 tumors and 2 of 11 Gleason score
      3-6 tumors (P < 0.01). These results suggest that PPARalpha is found and
      functional in human prostate and is down-regulated by androgens. The role of
      PPARalpha may be to integrate dietary fatty acid and steroid hormone signaling
      pathways, and its overexpression in advanced prostate cancer may indicate a role
      in tumor progression with the potential involvement of dietary factors.

PMID- 10955812
TI  - Evidence for a dose-response effect between p53 (but not p21WAF1/Cip1) protein
      concentrations, survival, and responsiveness in patients with epithelial ovarian
      cancer treated with platinum-based chemotherapy.
AB  - The prognostic values of p53 and of its downstream mediator p21WAF1/Cip1 in
      patients receiving adjuvant chemotherapy for epithelial ovarian cancer have not
      been clearly established. Tumor extracts from a series of 120 patients treated
      postsurgically with cisplatin or carboplatin alone or together with other
      chemotherapeutics for primary ovarian carcinoma were assayed both for p53 protein
      by an immunofluorometric assay developed by us and for p21 protein by a
      commercially available immunoassay. Relative risks (RRs) for cancer relapse and
      death after 24 months of follow-up were determined by multivariate Cox regression
      analysis. Disease-free (DFS) and overall survival (OS) probabilities were also
      examined by the Kaplan-Meier method and log-rank tests. All other procedures were
      similarly nonparametric and based on two-sided tests of significance.
      Concentrations of p53 were elevated in patients with advanced stage disease (P =
      0.02) or poorly differentiated (P = 0.03), suboptimally debulked tumors (P =
      0.02), as well as in patients who failed to respond to chemotherapy (P = 0.03),
      as assessed by computed tomography scanning, serum CA125 determination, and
      second-look laparotomy. Statistically significant associations between
      concentrations of p53 and p21 were not found, nor were relationships demonstrated
      between concentrations of p21 and other clinicopathological variables or
      treatment response. Univariate analysis showed that p53 concentrations above the
      median indicated significantly higher risks for relapse (P = 0.04) and death (P <
      0.01) and showed trends for increasing risks for relapse (P = 0.04) and death (P
      < 0.01) when p53 was considered as a four-level categorical variable.
      Multivariate analyses adjusted for age, stage, grade, and residual tumor size
      confirmed these observations (RR = 1.50; P = 0.05 for DFS and RR = 1.92; P = 0.03
      for OS) for median-dichotomized p53, but the trends were of borderline
      significance (P = 0.09 for DFS and P = 0.07 for OS). In contrast, p21 positivity
      was not a significant predictor of favorable outcome in univariate survival
      analysis, and use of a three-level variable combining positivity or negativity
      status for both p53 and p21 did not yield greater separation of patients into
      risk groups (P = 0.07 for DFS and P = 0.06 for OS) than the use of p53 alone.
      Assessment of p53 expression may be an independent indicator of poor prognosis in
      ovarian cancer patients treated with adjuvant chemotherapy. The prognostic value
      of p21 expression, however, could not be demonstrated in our series of ovarian
      cancer patients.

PMID- 10955811
TI  - Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3,
      is decreased in psoriasis and skin cancer.
AB  - Tazarotene-induced gene-3 (TIG-3), isolated from human keratinocytes treated with
      the retinoic acid receptor-selective retinoid Tazarotene, is homologous to H-rev,
      a class II tumor suppressor. TIG-3 gene localized to chromosome 11q23, a site of
      loss of heterozygosity in several malignancies. Retinoids influence epidermal
      differentiation and are used to treat and prevent skin cancer. Therefore, we
      studied TIG-3 mRNA expression in psoriasis and in basal and SCCs by in situ
      hybridization and a quantitative QT-RT-PCR assay. Psoriasis lesions had
      significantly lower staining (median, 3) than paired normal control skin (median,
      4; P = 0.012). TIG-3 mRNA was significantly higher in normal control skin (P =
      0.001), in paired adjacent skin (median, 3; P = 0.007), and in overlying
      epidermis (median, 3.0; P = 0.0001) than in 21 SCC specimens as a group (median,
      1.5).

PMID- 10955813
TI  - Overexpression of H-Ryk in epithelial ovarian cancer: prognostic significance of
      receptor expression.
AB  - H-Ryk is an atypical receptor tyrosine kinase that is expressed in a
      differentiation-specific manner in epithelial tissues. We have previously shown
      by in situ hybridization and immunohistochemistry that H-Ryk is overexpressed in
      malignant ovarian tumors. In addition, we have demonstrated that overexpression
      of H-Ryk is transforming in vitro and in vivo. To evaluate whether expression of
      H-Ryk is a prognostic factor in epithelial ovarian cancer, we carried out a
      retrospective study of 88 primary malignant ovarian tumors (28 serous tumors, 11
      mucinous tumors, 29 endometrioid tumors, 13 clear cell tumors, 3 malignant mixed
      Mullerian tumors, 1 mixed epithelial tumor, 1 primary peritoneal tumor, 1
      undifferentiated tumor, and 1 transitional carcinoma) diagnosed between 1990 and
      1993 using immunohistochemistry. On univariate analysis, overall survival
      decreased significantly with age (P = 0.01); in patients with International
      Federation of Gynecology and Obstetrics (FIGO) stage II (P = 0.008), FIGO stage
      III (P < 0.001), and FIGO stage IV (P < 0.001) disease; and in patients with
      residual disease (residual disease < or = 2 cm, P = 0.007; residual disease > 2
      cm, P < 0.001) after surgery. In addition, overexpression of the H-Ryk receptor
      in malignant epithelium (P = 0.04) and blood vessel (P = 0.01) was associated
      with a significantly decreased overall survival. H-Ryk blood vessel
      overexpression (P = 0.03), residual disease > 2 cm (P = 0.006), and residual
      disease < or = 2 cm (P = 0.01) conferred a significantly shorter progression-free
      survival. No correlation was found between H-Ryk overexpression and age,
      histological subtype, degree of differentiation, FIGO stage, or residual disease.
      Overall, after adjustment for all of the prognostic factors by multivariate
      analysis (Cox proportional hazards model), residual disease was the most powerful
      prognostic indicator for overall survival (P < 0.001) and progression-free
      survival (P = 0.01) in this patient subset. This implies that H-Ryk acts
      cooperatively with other biological factors in the pathogenesis of ovarian
      cancer.

PMID- 10955814
TI  - Significance of macrophage chemoattractant protein-1 in macrophage recruitment,
      angiogenesis, and survival in human breast cancer.
AB  - Tumor cells stimulate the formation of stroma that secretes various mediators
      pivotal for tumor growth, including growth factors, cytokines, and proteases.
      However, little is known about the local regulation of these soluble mediators in
      the human tumor microenvironment. In this study, the local expression of
      cytokines, chemokines, and angiogenic factors was investigated in primary breast
      cancer tissue. The concentrations of interleukin (IL)-1, IL-4, IL-6, IL-10, IL
      12, tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-8, macrophage
      chemoattractant protein (MCP)-1, epithelial-neutrophil activating peptide-78,
      vascular endothelial growth factor, and thymidine phosphorylase (TP) were
      measured in 151 primary breast cancer extracts by ELISA. Tumor-associated
      macrophages (TAMs) were also examined by immunohistochemistry with anti-CD68
      antibodies. The correlation between soluble mediators and the relationship
      between TAM count and soluble mediators were evaluated. MCP-1 concentration was
      correlated significantly with the level of vascular endothelial growth factor,
      TP, TNF-alpha, and IL-8, which are potent angiogenic factors. IL-4 concentration
      was correlated significantly with IL-8 and IL-10. On the other hand, an inverse
      association was observed between TP and IL-12. The level of MCP-1 was associated
      significantly with TAM accumulation. In the immunohistochemical analysis, MCP-1
      expression was observed in both infiltrating macrophages and tumor cells.
      Prognostic analysis revealed that high expression of MCP-1, as well as of VEGF,
      was a significant indicator of early relapse. These findings indicate that
      interaction between the immune network system and angiogenesis is important for
      progression of human breast cancer, and that MCP-1 may play an important role in
      the regulation of angiogenesis and the immune system.

PMID- 10955815
TI  - Inhibition of gelatinolytic activity in tumor tissues by synthetic matrix
      metalloproteinase inhibitor: application of film in situ zymography.
AB  - Inhibition of gelatinolytic activity in implanted tumor tissues by oral
      administration of N-biphenyl sulfonyl-phenylalanine hydroxamic acid (BPHA), a
      selective matrix metalloproteinase (MMP) inhibitor, was demonstrated by means of
      film in situ zymography (FIZ). Active-MMP-2 but not pro-MMP-2 showed
      gelatinolytic activity in FIZ, whereas both forms of MMP-2 were found to be
      active in conventional zymography. A mixture of either tissue inhibitors of
      metalloproteinase-2 or BPHA with active-MMP-2 resulted in inhibition of
      gelatinolytic activity in FIZ but not in zymography. Thus, FIZ, but not
      zymography, could detect net MMP activity in tumor tissues. When a specimen from
      Ma44 human lung cancer xenograft was subjected to FIZ, gelatinolytic activity was
      markedly detected with precise localization in the tumor tissues. The
      gelatinolytic activity detected in Ma44 tumor tissues was found to be mainly
      derived from MMPs because the gelatin-degrading activity was inhibited by
      pretreatment of the tumor specimen with MMP inhibitors. Oral administration of
      BPHA but not (-)BPHA, an enantiomer of BPHA lacking MMP inhibitory activity,
      successfully inhibited the MMP activity localized in Ma44 tumor tissues in both a
      dose-dependent and time-dependent manner. The data presented in this report
      showed for the first time that oral administration of synthetic MMP inhibitor
      could inhibit the net activity of MMP activity in tumor tissues, suggesting the
      usefulness of the FIZ technique for determining the effective dose of MMP
      inhibitor in clinical studies.

PMID- 10955816
TI  - Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate.
AB  - Medroxyprogesterone acetate (MPA) is a drug commonly used in endocrine therapy
      for advanced or recurrent breast cancer and endometrial cancer. The drug is
      extensively metabolized in the intestinal mucosa and in the liver. Cytochrome
      P450s (CYPs) involved in the metabolism of MPA were identified by using human
      liver microsomes and recombinant human CYPs. In this study, the overall
      metabolism of MPA was determined as the disappearance of the parent drug from an
      incubation mixture. The disappearance of MPA in human liver microsomes varied 2.6
      fold among the 18 samples studied. The disappearance of MPA in the same panel of
      18 human liver microsomes was significantly correlated with triazolam alpha
      hydroxylase activity, a marker activity of CYP3A (r = 0.764; P < 0.001).
      Ketoconazole, an inhibitor of CYP3A4, potently inhibited the disappearance of MPA
      in 18 human liver microsomes. Anti-CYP3A antibody also inhibited 86% of the
      disappearance of MPA in human liver microsomes. Although sulfaphenazole (an
      inhibitor of CYP2C9) and S-mephenytoin (an inhibitor of CYP2C19) partially
      inhibited the disappearance of MPA, no effect of the anti-CYP2C antibody was
      observed. The disappearance of MPA did not correlate with either the activity
      metabolized via CYP2C9 (diclofenac 4'-hydroxylase activity) or the activity
      metabolized via CYP2C19 (S-mephenytoin 4'-hydroxylase activity). Among the 12
      recombinant human CYPs (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18,
      CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5) studied, only CYP3A4 showed
      metabolic activity of MPA. These results suggest that CYP3A4 is mainly involved
      in the overall metabolism of MPA in human liver microsomes.

PMID- 10955817
TI  - Sensitivity to 5,10-dideazatetrahydrofolate is fully conserved in a murine
      leukemia cell line highly resistant to methotrexate due to impaired transport
      mediated by the reduced folate carrier.
AB  - A murine leukemia cell line was identified that is highly resistant to
      methotrexate (MTX), due to impaired transport, but fully sensitive to 5,10
      dideazatetrahydrofolate (DDATHF). A valine-to-methionine substitution at amino
      acid 104 in the reduced folate carrier (RFC1) explains this disparity in drug
      resistance. Transfection of the V104M cDNA into an RFC1-deficient cell line
      markedly increased DDATHF influx (32x) but only modestly increased influx of MTX
      and 5-formyltetrahydrofolate (4- and 6-fold, respectively). The growth inhibition
      or growth requirements for these folates fell by factors of 18, 2, and 4,
      respectively, in the transfectant. Preservation of DDATHF influx in cells with
      V104M RFC1 resulted in even greater preservation (60%) of the exchangeable drug
      level. Another major element in the preservation of DDATHF activity was the
      impact of the mutated carrier on cellular folate pools. For folic acid, folate
      pools were essentially unchanged but DDATHF polyglutamate levels decreased in
      lines that express the V104M carrier. However, with 5-formyltetrahydrofolate as
      the growth source, there was a marked decrease in folate pools in the lines
      carrying the mutated carrier, and DDATHF polyglutamate levels were unchanged.
      Hence, DDATHF activity was preserved in cells with V104M RFC1 due to (a) relative
      conservation of DDATHF transport, and (b) depletion of cellular THF cofactors
      with diminishing folate cofactor competition at folylpolyglutamate synthetase and
      possibly glycinamide ribonucleotide formyltransferase. Hence, resistance to one
      antifolate, in this case MTX, because of a loss of RFC1 transport activity need
      not exclude the subsequent utility of another antifolate that uses the same
      carrier.

PMID- 10955818
TI  - Induction of a heat shock factor 1-dependent stress response alters the cytotoxic
      activity of hsp90-binding agents.
AB  - In addition to its classic role in the cellular stress response, heat shock
      protein 90 (Hsp90) plays a critical but less well appreciated role in regulating
      signal transduction pathways that control cell growth and survival under basal,
      nonstress conditions. Over the past 5 years, the antitumor antibiotics
      geldanamycin and radicicol have become recognized as selective Hsp90-binding
      agents (HBA) with a novel ability to alter the activity of many of the receptors,
      kinases, and transcription factors involved in these cancer-associated pathways.
      As a consequence of their interaction with Hsp90, however, these agents also
      induce a marked cellular heat shock response. To study the mechanism of this
      response and assess its relevance to the anticancer action of the HBA, we
      verified that the compounds could activate a reporter construct containing
      consensus binding sites for heat shock factor 1 (HSF1), the major transcriptional
      regulator of the vertebrate heat shock response. We then used transformed
      fibroblasts derived from HSF1 knock-out mice to show that unlike conventional
      chemotherapeutics, HBA increased the synthesis and cellular levels of heat shock
      proteins in an HSF1-dependent manner. Compared with transformed fibroblasts
      derived from wild-type mice, HSF1 knock-out cells were significantly more
      sensitive to the cytotoxic effects of HBA but not to doxorubicin or cisplatin.
      Consistent with these in vitro data, we found that systemic administration of an
      HBA led to marked increases in the level of Hsp72 in both normal mouse tissues
      and human tumor xenografts. We conclude that HBA are useful probes for studying
      molecular mechanisms regulating the heat shock response both in cells and in
      whole animals. Moreover, induction of the heat shock response by HBA will be an
      important consideration in the clinical application of these drugs, both in terms
      of modulating their cytotoxic activity as well as monitoring their biological
      activity in individual patients.

PMID- 10955819
TI  - The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer
      growth.
AB  - At least 70% of small cell lung cancers express the Kit receptor tyrosine kinase
      and its ligand, stem cell factor (SCF). Numerous lines of evidence have
      demonstrated that this coexpression constitutes a functional autocrine loop,
      suggesting that inhibitors of Kit tyrosine kinase activity could have therapeutic
      efficacy in this disease. STI571, formerly known as CGP 57148B, is a p.o.
      bioavailable 2-phenylaminopyrimide derivative that was designed as an Abl
      tyrosine kinase inhibitor, but also has efficacy against the platelet-derived
      growth factor receptor and Kit in vitro. Pretreatment of the H526 small cell lung
      cancer (SCLC) cell line with STI571 inhibited SCF-mediated Kit activation with an
      IC50 of 0.1 microM as measured by inhibition of receptor tyrosine phosphorylation
      and 0.2 microM as measured by immune complex kinase assay. This paralleled the
      inhibition of SCF-mediated growth by STI571, which had an IC50 of approximately
      0.3 microM. Growth inhibition in SCF-containing medium was accompanied by
      induction of apoptosis. STI571 efficiently blocked SCF-mediated activation of
      mitogen-activated protein kinase and Akt, but did not affect insulin-like growth
      factor-1 or serum-mediated mitogen-activated protein kinase or Akt activation.
      Growth of five of six SCLC cell lines in medium containing 10% FCS was inhibited
      by STI571 with an IC50 of approximately 5 microM. Growth inhibition in serum
      containing medium appeared to be cytostatic in nature because no increase in
      apoptosis was observed. Despite this growth inhibition, STI571 failed to enhance
      the cytotoxicity of either carboplatinum or etoposide when coadministered.
      However, taken together with the minimal toxicity that this compound has shown in
      preclinical studies, these data suggest that STI571 could have a role in the
      treatment of SCLC, possibly to block or slow recurrence after chemotherapy
      induced remissions.

PMID- 10955820
TI  - In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma
      xenografted into nude mice.
AB  - The lack of new highly efficacious drugs for cancer treatment promotes the search
      for innovative therapeutic modalities. The authors reported the results leading
      to the definition of parameters needed to demonstrate a possible
      radiopotentiation by topotecan (TPT) on two representative human
      rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of
      radiopotentiation with different doses of topotecan showed that concomitant
      association of topotecan and RT for 5 consecutive days provided a synergistic
      therapeutic effect. Response rates were statistically higher with the
      radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of
      this combination compared with the sum of the antitumoral activity of these
      treatments separately administrated were 1.54 and 1.60, respectively, on both
      rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy at
      the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different
      from that of radiotherapy at the dose of 40 Gy. According to microscopy results,
      the analyses performed at different periods after topotecan treatment alone,
      radiotherapy alone, and their combination seemed to show that tumoral
      repopulation by malignant cells is as fast as the dose of radiotherapy and/or
      topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were
      similar to those obtained with the association of topotecan at the dose of 12.5
      mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and
      pathological results are consistent with a radiopotentiation effect of topotecan
      on the two xenografted human rhabdomyosarcomas and are currently leading to the
      design of clinical studies.

PMID- 10955821
TI  - Synergistic interaction between anti-p185HER-2 ricin A chain immunotoxins and
      radionuclide conjugates for inhibiting growth of ovarian and breast cancer cells
      that overexpress HER-2.
AB  - Radionuclide conjugates or ricin A chain (RTA) immunotoxins that target pl85HER-2
      have partially inhibited the growth of human ovarian cancer xenografts in athymic
      mice but generally have not cured mice bearing human tumor transplants. The
      present study was undertaken to explore whether a combination of ionizing
      radiation and an immunotoxin could exert additive or synergistic cytotoxicity in
      culture and in vivo against cancer cells that overexpress p185HER-2. In cell
      culture, treatment with 200-2000 cGy external beam irradiation followed by
      incubation with TA1-anti-pl85mHER2-RTA immunotoxin (TA1-RTA) produced synergistic
      inhibition of clonogenic growth of ovarian and breast cancer cells that expressed
      > 10(6) pl85HER-2 receptors/cell. The effect on cell survival correlated with an
      inhibition of DNA repair. A prior study (F. J. Xu et al, Nucl. Med. Biol., 24:
      451-460, 1997) compared the biodistribution of radionuclide conjugates prepared
      with monoclonal antibodies that bind to different epitopes on the extracellular
      domain of pl85HER-2 and found optimal tumor uptake with the 520C9 antibody, which
      did not compete with TA1 for binding to the receptor. In this report, the TA1-RTA
      immunotoxin and the 131I-labeled 520C9 radionuclide conjugate could each inhibit
      the growth of clone-9002-18 xenografts in athymic mice but did not yield long
      term survivors using maximally tolerated doses of each agent. When TA1-RTA and
      131I-labeled 520C9 were used in combination, a greater inhibition of tumor growth
      was obtained than with either single agent. Similarly, survival with the combined
      treatment was significantly prolonged (P = 0.004) relative to treatment with
      immunotoxin or radionuclide conjugate alone. After treatment with an optimal
      combination of immunotoxin and radionuclide conjugate, 50% of mice survived >300
      days, whereas controls succumbed with a median survival of 36 days. These results
      suggest that combinations of immunotoxins and radionuclide conjugates deserve
      further evaluation for the treatment of cancers that overexpress pl85HER-2.

PMID- 10955822
TI  - Oncolytic herpes simplex virus-1 lacking ICP34.5 induces p53-independent death
      and is efficacious against chemotherapy-resistant ovarian cancer.
AB  - Replication-restricted herpes simplex virus-1 (HSV-1) strains lacking ICP34.5 are
      emerging as powerful anticancer agents against several solid tumors including
      epithelial ovarian cancer (EOC). Although chemotherapy-resistant tumors would be
      likely candidates for treatment with HSV-1 mutants lacking ICP34.5, the efficacy
      of these mutants on such tumors is unknown. In the present study, we investigated
      whether chemotherapy resistance affects the response of ovarian cancer cells to
      HSV-R3616, an ICP34.5-deficient, replication-restricted HSV-1. Primary EOC
      cultures obtained from patients who varied in their responses to
      platinum/paclitaxel induction chemotherapy displayed similar sensitivity to HSV
      R3616. Similarly, chemotherapy-sensitive ovarian cancer cells A2780 and PA-1,
      possessing wild-type p53, and their respective chemotherapy-resistant clones
      A2780/200CP, lacking p53 function, and PA-1/E6, permanently expressing the HPV E6
      gene, were equally sensitive to HSV oncolysis. Because wild-type HSV can kill
      cells by apoptosis and nonapoptotic mechanisms, we investigated the involvement
      of apoptosis and the role of the p53 tumor suppressor gene in oncolysis induced
      by HSV-R3616. Infection of ovarian cancer cell lines by HSV-R3616 was followed by
      cell death via apoptosis or nonapoptotic mechanisms as noted by morphology, cell
      cycle analysis, and in situ TUNEL assay. p53 protein levels remained unchanged,
      and Bax protein levels decreased in cells possessing intact p53 and that mainly
      underwent HSV-induced apoptosis. Loss of p53 function did not affect the
      frequency or rate of apoptosis or the sensitivity of EOC cells to the oncolytic
      effect of HSV-R3616. These results suggest that recombinant HSV-1 lacking ICP34.5
      is capable of killing ovarian cancer cells that lack p53 function, resist
      apoptosis, and/or are chemotherapy resistant. These data support the hypothesis
      that HSV-based oncolytic therapy may be efficacious in chemotherapy-resistant
      tumors, including tumors that are deficient in p53.

PMID- 10955824
TI  - Tumor biology: use of tiled images in conjunction with measurements of cellular
      proliferation and death in response to drug treatments.
AB  - Tumor growth is dependent on the balance between cell proliferation and cell
      death, and these events occur heterogenously within an individual tumor. We
      present a methodology that provides integrative information about cell kinetics,
      cell death, and cell growth within individual tumors in animals treated with
      cytotoxic chemotherapeutic agents. Using HCT-116 and NCI-H460 cells, human
      colonic adenocarcinoma and non-small cell lung cells, respectively, traditional
      xenograft studies were performed. The tumor-bearing animals were treated with
      cyclophosphamide (Cytoxan), gemcitabine (Gemzar), or mitomycin C, and extensive
      analysis of the tumors was studied. Cell kinetics were evaluated by measuring the
      apoptotic and proliferation indices. The ability to image an entire tumor section
      using "tiling" by creating a large montage from many high-resolution images makes
      it possible to identify regional differences within areas of tumor and to
      demonstrate differences in these tumor regions after treatment with selected
      chemotherapeutic agents. Two specific areas within tumors have been identified:
      (a) areas of viable cells within the cell cycle, determined by bromodeoxyuridine
      and/or morphological characteristics determined by hematoxylin staining; and (b)
      areas of necrosis determined by the absence of bromodeoxyuridine and
      proliferating cell nuclear antigen-labeled cells coupled with morphological
      changes. By standardizing the tumor size to 100 mm2, different patterns of tumor
      responses to chemotherapeutic agents were determined. By creating such tiled
      images and by quantitating cell cycle kinetics, it is possible to gain a more
      complete understanding of tumor growth and response to treatment, leading to the
      development of more reliable methods for assessing the clinical behavior of
      anticancer drugs.

PMID- 10955823
TI  - Efficient inhibition of in vivo human malignant glioma growth and angiogenesis by
      interferon-beta treatment at early stage of tumor development.
AB  - Malignant gliomas are highly angiogenic and aggressive tumors. IFN-beta has been
      used for the treatment of patients with malignant glioma; however, its antitumor
      mechanism in vivo remains unclear. To understand the in vivo antitumor effect and
      mechanism of recombinant human IFN-beta (rhIFN-beta) depending on the stages of
      tumor development or progression, we used orthotopic xenograft brain tumors
      generated by stereotactic intracerebral implantation of U-87 human glioma cells
      in nude mice. Mice bearing tumors 7 days (group 1) and 21 days (group 2)
      postimplant were treated with 2 x 10(5) IU/day of rhIFN-beta or saline i.p. for
      15 days, respectively. Tumor growth was suppressed by 69.6% in group 1 and 10.8%
      in group 2 compared with tumors of each control group treated with saline. rhIFN
      beta-treated group 1 animals showed 38% reduction in vascularization along with a
      2.5-fold increase of the apoptotic index and no change in the proliferative index
      as compared with untreated tumors. The expression level of vascular endothelial
      cell growth factor and basic fibroblast growth factor was not affected by rhIFN
      beta treatment. rhIFN-beta showed inhibitory activity on proliferation of U-87
      cells, human umbilical vein endothelial cells, and PAM 212 murine keratinocytes
      in vitro. Our results indicate that the in vivo antitumor effect of rhIFN-beta on
      malignant gliomas may be mediated, at least in part, via angiogenesis inhibition
      rather than antiproliferative activity and that rhIFN-beta may be more effective
      for the treatment of malignant glioma patients at an early stage with minimal or
      microscopic tumor burdens rather than at an advanced stage of tumor development.

PMID- 10955825
TI  - 1alpha,25-Dihydroxyvitamin D3 down-regulates estrogen receptor abundance and
      suppresses estrogen actions in MCF-7 human breast cancer cells.
AB  - 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D,
      is a potent inhibitor of breast cancer cell growth. Because the estrogen receptor
      (ER) plays a key role in breast cancer progression, we have studied the effects
      of 1,25(OH)2D3 on the regulation of ER in the estrogen-responsive MCF-7 human
      breast cancer cell line, which is known to predominantly express ERalpha.
      1,25(OH)2D3 causes significant inhibition of MCF-7 cell growth, and it also
      decreases the growth-stimulatory effect of 17beta-estradiol (E2). Treatment of
      MCF-7 cells with 1,25(OH)2D3 reduces ER levels in a dose-dependent manner, as
      shown by ligand binding assays and Western blot analysis. The 1,25(OH)2D3
      analogues EB-1089, KH-1060, Ro 27-0574, and Ro 23-7553 are more potent than
      1,25(OH)2D3 in both their antiproliferative actions as well as ER down
      regulation. There is a striking correlation (R2 = 0.98) between the growth
      inhibitory actions of 1,25(OH)2D3 or analogues and their ability to down-regulate
      ER levels. Treatment with 1,25(OH)2D3 shows that the reduction in ER is
      accompanied by a significant decrease in the steady-state levels of ER mRNA. The
      decrease in ER mRNA is not abolished by the protein synthesis inhibitor
      cycloheximide. Inhibition of mRNA synthesis with actinomycin D reveals no
      significant differences between ER mRNA half-life in control and 1,25(OH)2D3
      treated cells. Nuclear run-on experiments demonstrate significant decreases in ER
      gene transcription at the end of 17 h of treatment with 1,25(OH)2D3. These
      findings indicate that 1,25(OH)2D3 exerts a direct negative effect on ER gene
      transcription. Coincident with the decrease in ER levels there is an attenuation
      of E2-mediated bioresponses after 1,25(OH)2D3 treatment. Induction of
      progesterone receptor by E2 is suppressed by 1,25(OH)2D3, and the E2-mediated
      increase in breast cancer susceptibility gene (BRCA1) protein is reduced by
      1,25(OH)2D3 treatment. Overall, these results suggest that the antiproliferative
      effects of 1,25(OH)2D3 and its analogues on MCF-7 cells could partially be
      mediated through their action to down-regulate ER levels and thereby attenuate
      estrogenic bioresponses, including breast cancer cell growth.

PMID- 10955827
TI  - Oral administration of Escherichia coli glutamic acid decarboxylase has
      immunomodulatory effects in streptozotocin-induced diabetes.
AB  - The extent of destruction of insulin-secreting beta cells of the Islets of
      Langerhans was investigated in an animal model using oral administration of
      glutamic acid decarboxylase (GAD) isolated from Escherichia coli. The extent of
      lymphocytic infiltration of the pancreatic Islet cells and the severity of
      diabetes were significantly reduced by oral administration of GAD to rats 14 days
      before intraperitoneal injections of streptozotocin (STZ, 40 mg/kg body wt on 5
      consecutive days). In addition, oral administration of GAD to rats 14 days before
      or 3 days after STZ treatment significantly (p <0.05) reduced the levels of GAD
      specific antibodies and improved the in vitro proliferative response of
      splenocytes to concanavalin A (Con A). These data demonstrate that oral GAD
      administration probably generates active cellular mechanisms which suppress the
      disease and therefore raise the possibility of using E. coli GAD as a new means
      for the immunomodulation of autoimmune diabetes.

PMID- 10955826
TI  - Antitumor effect of alpha-galactosylceramide (KRN7000) on spontaneous hepatic
      metastases requires endogenous interleukin 12 in the liver.
AB  - Hepatic metastasis is a major clinical problem in cancer treatment. We examined
      antitumor activity of alpha-galactosylceramide (KRN7000) on mice with spontaneous
      liver metastases of reticulum cell sarcoma M5076 tumor cells (spontaneous
      metastasis model). In this model, all mice that were s.c. challenged with one
      million tumor cells developed a solid s.c. mass by day 7 and died of hepatic
      metastases. In the current study, we administered 100 microg/kg of KRN7000 to the
      model mice on days 7, 11, and 15. This treatment suppressed the growth of
      established liver metastases and resulted in the prolongation of survival time.
      Fluorescence-activated cell sorter analysis of phenotypes of spleen cells,
      hepatic lymphocytes, and regional lymph node cells around the s.c. tumor revealed
      that CD3+NK1.1+ (NKT) cells increased in hepatic lymphocytes of the KRN7000
      treated mice. Cytotoxic activity and IFN-gamma production of hepatic lymphocytes
      were augmented in comparison with those of spleen cells and regional LN cells. At
      the same time, interleukin (IL)-12 production of hepatic lymphocytes was markedly
      enhanced. Neutralization of IL-12 using a blocking monoclonal antibody diminished
      the prolonged survival time. These results showed that the in vivo antitumor
      effects of KRN7000 on spontaneous liver metastases were dependent on the
      endogenous IL-12 production, where NKT cells in the liver are suggested to be
      involved. Adjuvant immunotherapy using KRN7000 could be a promising modality for
      the prevention of postoperative liver metastases.

PMID- 10955828
TI  - Expression of the p53 protein in oral squamous cell carcinomas associated with
      Epstein-Barr virus.
AB  - The behaviour of the p53 protein has been investigated in some human carcinomas
      associated with Epstein-Barr virus (EBV) but not in EBV-positive oral squamous
      cell carcinomas (OSCC). The present study aimed to compare the p53 protein
      expression in EBV-positive OSCC with that in EBV-negative OSCC. The cases had
      been gathered in a study previously published. An immunohistochemical technique
      with BP53-12 monoclonal antibody was applied on 74 of the 107 OSCC from the
      earlier work. The nuclear or cytoplasmic expression of the p53 protein was
      classified as, absent (0% of neoplastic cells positive), mild (<25% positive),
      moderate (25-30% positive), or extensive (>50% positive). The p53 protein was
      expressed by 60.8% of the OSCC. Out of the fourteen EBV-positive OSCC, 57.1% (8
      cases) expressed p53, always in the nucleus and never in the cytoplasm. Of the 60
      EBV-negative OSCC, 61.6% (37 cases) expressed the p53 protein. Of 37 cases 33
      (89.1%) showed nuclear expression of p53 and nineteen cases (51.3%) revealed
      cytoplasmic expression. There was a statistically significant inverse correlation
      between cytoplasmic expression of the p53 protein and the presence of EBV DNA (p
      <0.01). Thus, the EBV-positive tumours less frequently expressed p53 in the
      cytoplasm. No evidence of an accumulation of the p53 protein in OSCC associated
      with EBV was recorded.

PMID- 10955829
TI  - Influence of dopamine energic pharmacology drugs on secretion of the
      adrenocorticotropic hormone from the hypophysis.
AB  - To elucidate the role of dopamine as a neuromediator in the adrenocorticotropic
      hormone (ACTH) secretion, investigations were carried out with dopaminergic
      pharmacology drugs on male white Wistar rats. In the first series of experiments,
      the effects of 200 mg/kg body wt L-DOPA, of the combination of 200 mg/kg L-DOPA
      and 50 mg/kg body wt carbidopa, and of 2.5 mg/kg body wt bromocriptine, after a
      single intraperitoneal injection of ACTH in the serum of rats after 30, 90 and
      120 min, following the injection, were studied. In the second series of
      experiments, the effect of 200 mg/kg body wt L-DOPA, of the combination of 200
      mg/kg body wt L-DOPA and 50 mg/kg body wt carbidopa, of 1 mg/kg body wt
      bromocriptine, after intraperitoneal injection, on the concentration of ACTH in
      the serum within 7 days, were assessed. The inhibition of agonists of dopamine
      after ACTH secretion with repeated application has been shown. Using a
      radioimmunology assay with test kits, the amount of ACTH in the serum was
      determined.

PMID- 10955830
TI  - Detection and investigation of Campylobacter jejuni by polymerase chain reaction
      restriction fragment length polymorphism analysis.
AB  - A molecular typing approach for Campylobacter jejuni with restriction fragment
      length polymorphism (RFLP) analysis of the flagellin gene flaA in C. jejuni, was
      generated and studied. Using polymerase chain reaction (PCR)-RFLP with the
      restriction endonuclease Mbo I, it was demonstrated that C. jejuni could be
      divided into four types. Genotypic analysis of C. jejuni by PCR-RFLP is a
      valuable technique for epidemiological typing.

PMID- 10955831
TI  - Antifungal potential of some higher plants against Fusarium udum causing wilt
      disease of Cajanus cajan.
AB  - The fungitoxic effects of different plant extracts on Fusarium udum, which causes
      wilt disease of Cajanus cajan in vitro and in vivo, were examined. The complete
      arrest of the radial growth of the pathogen occurred at a 10% concentration of
      leaf extract from Adenocallyma alliaceum. A leaf extract of Citrus medica, a root
      extract of Asparagus adscendens, rhizome extracts of Curcuma longa and Zingiber
      officinale, and a bulb extract of Allium sativum inhibited up to 100% growth at
      higher concentrations. A. alliaceum controlled the disease up to 100% by amending
      its 4% powder in unsterilized soil and 2% in sterilized soil. The population of
      F. udum was found to be markedly reduced following treatments with plant powders.

PMID- 10955832
TI  - Activity pattern of natural and synthetic antibacterial agents among hospital
      isolates.
AB  - The antibacterial pattern of tetracycline and bactrim was compared with that of
      the chloroform extract of two Pseudomonas strains using ten hospital strains each
      of Staphylococcus aureus and Escherichia coli. There was no perfect correlation
      between isolate source, antibiotic type and sensitivity. Both the synthetic and
      natural antibiotic agent exhibited antibacterial activities against resistant
      hospital isolates at high concentrations.

PMID- 10955833
TI  - Plasmid-mediated catabolism of dicamba by Pseudomonas species strain PXM.
AB  - Pseudomonas species strain PXM, which is able to use dicamba (3,6-dichloro-2
      methoxybenzoic acid; CAS 1918-00-9, Banvel) as its sole carbon source for growth,
      has been isolated. The catabolism of dicamba and some of its putative metabolic
      descendants correlates with the presence of a large and unstable plasmid.

PMID- 10955834
TI  - Predicting human oral bioavailability of a compound: development of a novel
      quantitative structure-bioavailability relationship.
AB  - PURPOSE: The purpose of this investigation was to develop a quantitative
      structure-bioavailability relationship (QSBR) model for drug discovery and
      development. METHODS: A database of drugs with human oral bioavailability was
      assembled in electronic form with structure in SMILES format. Using that
      database, a stepwise regression procedure was used to link oral bioavailability
      in humans and substructural fragments in drugs. The regression model was compared
      with Lipinski's Rule of Five. RESULTS: The human oral bioavailability database
      contains 591 compounds. A regression model employing 85 descriptors was built to
      predict the human oral bioavailability of a compound based on its molecular
      structure. Compared to Lipinski's Rule of Five, the false negative predictions
      were reduced from 5% to 3% while the false positive predictions decreased from
      78% to 53%. A set of substructural descriptors was identified to show which
      fragments tend to increase/decrease human oral bioavailability. CONCLUSIONS: A
      novel quantitative structure-bioavailability relationship (QSBR) was developed.
      Despite a large degree of experimental error, the model was reasonably predictive
      and stood up to cross-validation. When compared to Lipinski's Rule of Five, the
      QSBR model was able to reduce false positive predictions.

PMID- 10955835
TI  - New insights into the pharmacokinetics and metabolism of (R,S)-ifosfamide in
      cancer patients using a population pharmacokinetic-metabolism model.
AB  - PURPOSE: To describe the pharmacokinetics of R- and S-Ifosfamide (IFF), and their
      respective 2 and 3 N-dechloroethylated (DCE) metabolites (R2-, R3-, S2, S3-DCE
      IFF) in cancer patients. METHODS: (R,S)-IFF was administered (1.5 g/m2) daily for
      5 days in 13 cancer patients. Plasma and urine samples were collected and
      analyzed using an enantioselective GC-MS method. An average of 97 observations
      per patient were simultaneously fitted using a pharmacokinetic-metabolism (PK-MB)
      model. A population PK analysis was performed using an iterative 2-stage method
      (IT2S). RESULTS: Auto-induction of IFF metabolism was observed over the 5 day
      period. Increases were seen in IFF clearance (R: 4 vs. 7 L/h; S: 5 vs. 10 L/h),
      and in the formation of DCE (R: 7 vs. 9%; S: 14 vs. 19%) and active metabolites
      (4-OHM-IFF; R: 71 vs. 77%; S: 67 vs. 71%). A novel finding of this analysis was
      that the renal excretion of the DCE metabolites was also induced. CONCLUSIONS:
      This population PK-MB model for (R,S)-IFF may be useful in the optimization of
      patient care, and gives new insight into the metabolism of (R,S)-IFF.

PMID- 10955837
TI  - Prediction of in vivo tissue distribution from in vitro data 1. Experiments with
      markers of aqueous spaces.
AB  - PURPOSE: The aim of this study was to evaluate the ability of an in vitro method
      of tissue distribution to accurately predict total water and extracellular
      aqueous spaces using marker compounds urea and inulin. METHODS: Slices (50-200
      mg) of all the major tissues in the rat were incubated with Hanks/HEPES pH7.4
      buffer containing 14C-urea and 3H-inulin for 2 h at 37 degrees C. Tissue weight
      was noted before and after incubation and the tissue-to-buffer ratios determined.
      RESULTS: 14C-Urea Kp estimates were generally greater than total tissue water due
      to tissue swelling, which varied widely among the tissues, up to 41% in muscle.
      In most cases, Kp values were much closer to in vivo values after correcting for
      the 14C-urea in the imbibed media (Kpcorr). The method was able to distinguish
      between 14C-urea and 3H-inulin Kp values and indicated that inulin occupied a
      smaller space than urea, which for the majority of tissues corresponded to the
      extracellular space. CONCLUSIONS: The Kp(corr) values for 14C-urea and Kp for 3H
      inulin were consistent with total tissue water and extracellular space for the
      majority of tissues studied, indicating their suitability as marker compounds for
      checking the viability of this in vitro method for estimating tissue
      distribution.

PMID- 10955836
TI  - Pharmacokinetic-pharmacodynamic analysis of the EEG effect of alfentanil in rats
      following beta-funaltrexamine-induced mu-opioid receptor "knockdown" in vivo.
AB  - PURPOSE: The objective of this investigation was to determine the influence of
      pre-treatment with the irreversible mu-opioid receptor antagonist beta
      funaltrexamine (beta-FNA) on the pharmacokinetic-pharmacodynamic (PK/PD)
      relationship of alfentanil in rats. METHODS: The PK/PD correlation of alfentanil
      (2 mg x kg(-1) intravenously in 20 min) was determined in chronically
      instrumented rats using amplitudes in the 0.5-4.5 Hz frequency band of the EEG as
      pharmacodynamic endpoint. Beta-FNA was administered intravenously (10 mg x kg(
      1)) either 35 min or 24 h prior to the PK/PD experiments. RESULTS: Pre-treatment
      with beta-FNA had no influence on the pharmacokinetics of alfentanil. The in vivo
      concentration-EEG effect relationships, however, were steeper and shifted towards
      higher concentrations with no difference between the 35-min and the 24-h pre
      treatment groups. Analysis of the data on basis of the operational model agonism
      revealed that the observed changes could be explained by a 70-80% reduction in
      alfentanil efficacy in beta-FNA pre-treated rats. This is consistent with results
      from an in vitro receptor bioassay showing a 40-60% reduction in the number of
      specific mu-opioid binding sites in the brain. CONCLUSIONS: This investigation
      confirms the validity of a previously postulated mechanism-based PK/PD model for
      the effect of synthetic opiates in rats.

PMID- 10955838
TI  - Permeability and diffusion in vitreous humor: implications for drug delivery.
AB  - PURPOSE: Previous experimental work suggests that convection may be important in
      determining the biodistribution of drugs implanted or injected in the vitreous
      humor. To develop accurate biodistribution models, the relative importance of
      diffusion and convection in intravitreal transport must be assessed. This
      requires knowledge of both the diffusivity of candidate drugs and the hydraulic
      conductivity of the vitreous humor. METHODS: Hydraulic conductivity of cadaveric
      bovine vitreous humor was measured by confined compression tests at constant
      loads of 0.15 and 0.2 N and analyzed numerically using a two-phase model.
      Diffusion coefficient of acid orange 8, a model compound, in the same medium was
      measured in a custom-built diffusion cell. RESULTS: Acid orange 8 diffusivity
      within vitreous humor is about half that in free solution. When viscous effects
      are properly accounted for, the hydraulic conductivity of bovine vitreous humor
      is 8.4+/-4.5 x 10(-7) cm2/Pa x s. CONCLUSIONS: We predict that convection does
      not contribute significantly to transport in the mouse eye, particularly for low
      molecular-weight compounds. For delivery to larger animals, such as humans we
      conclude that convection accounts for roughly 30% of the total intravitreal drug
      transport. This effect should be magnified for higher-molecular-weight compounds,
      which diffuse more slowly, and in glaucoma, which involves higher intraocular
      pressure and thus potentially faster convective flow. Thus, caution should be
      exercised in the extrapolation of small-animal-model biodistribution data to
      human scale.

PMID- 10955839
TI  - Air-interface condition promotes the formation of tight corneal epithelial cell
      layers for drug transport studies.
AB  - PURPOSE: To identify the growth conditions that would favor the development of a
      functional primary culture of pigmented rabbit corneal epithelial cells on a
      permeable support comparable to the intact tissue in bioelectric properties.
      METHODS: Rabbit corneal epithelial cells were isolated and cultured on precoated
      fibronectin/collagen/laminin permeable filters. Cells were grown at an air
      interface with supplemented DMEM/F12 medium. Immunofluorescence and electron
      microscopy techniques, respectively, were used to confirm cornea-specific marker
      and morphological features. Permeability of the cell layers to model polar
      compounds was evaluated using 14C-mannitol, fluorescein isothiocyanate (FITC) and
      fluorescein isothiocyanate-dextran of 4,000 molecular weight (FD4). RESULTS: We
      found that culturing the epithelial cells at an air-interface (AIC) was a
      critical factor in the formation of tight cell layer and that omitting fetal
      bovine serum and keeping the concentration of epidermal growth factor at 1 ng/ml
      were equally important. Phenotypically, the AIC cell layers were found to express
      cornea-specific 64 kD keratin. Compared with cells cultured under the liquid
      covered (LCC) condition, those cultured under AIC exhibited a significantly
      higher peak transepithelial electrical resistance (TEER) of up to 5 kOhm x cm2, a
      higher potential difference (PD) of up to 26 mV, and an estimated short-circuit
      current (Ieq) of 5 microA/cm2 after 7-8 days of culture. These values were
      comparable to those in the excised cornea. Consistent with the TEER, the AIC cell
      layers were 4-40 times less permeable to paracellular markers than their LCC
      counterpart. CONCLUSIONS: The AIC model merits further characterization of drug
      transport mechanisms as well as drug, formulation, physiological, and
      pathological factors influencing corneal epithelial drug transport.

PMID- 10955840
TI  - Stabilization of vinca alkaloids encapsulated in poly(lactide-co-glycolide)
      microspheres.
AB  - PURPOSE: The purpose of this study was to stabilize the vinca alkaloids,
      vincristine sulfate (VCR) and vinblastine sulfate (VBL), in poly(lactide-co
      glycolide) (PLGA) microspheres and to release the drugs in a sustained manner for
      more than a month. METHODS: An oil-in-oil emulsion-solvent extraction method was
      used to encapsulate VCR and VBL in PLGA50/50 microspheres. Stability and release
      kinetics of the drugs during the incubation at 37 degrees C in PBS/Tween 80 were
      assessed by HPLC. Degradation products were identified with HPLC-MS. RESULTS: VCR
      and VBL were encapsulated in PLGA microspheres unchanged. During the microsphere
      incubation, however, VCR degraded inside the particles with a t1/2 approximately
      7.5 days. The degradation product was identified by LC-MS as the deformyl
      derivative, commonly formed at acidic pH. VBL, which differs only by a stable
      methyl group in place of the N-formyl group in VCR, was completely stable in the
      PLGA microclimate. The neutralization of acidic PLGA microclimate by addition of
      3-10% Mg(OH)2 completely inhibited deformylation of VCR during release. but
      introduced a new degradation product formed under the more alkaline conditions
      used during the preparation. The substitution of Mg(OH)2 with a weaker base,
      ZnCO3, inhibited the formation of both degradation products resulting in VCR
      stabilization of >92% for 4 weeks. The optimal formulations of VCR (containing
      ZnCO3) and VBL (no additives) slowly and continuously released stable drugs for
      over a month. CONCLUSIONS: VCR and VBL were successfully stabilized and released
      in a sustained manner from PLGA microspheres. Co-encapsulation of ZnCO3
      stabilizes VCR against acid-catalyzed degradation during release from the polymer
      and minimizes VCR decomposition during encapsulation.

PMID- 10955842
TI  - Controlled release of liposomes from biodegradable dextran microspheres: a novel
      delivery concept.
AB  - PURPOSE: To design liposome-loaded microspheres, which release the liposomes in a
      time-controlled manner and in intact form. METHODS: Liposomes were encapsulated
      in biodegradable dextran-based microspheres, which were prepared using an aqueous
      two phase system consisting of poly(ethylene glycol) and methacrylated dextran.
      The effects of liposome size and membrane fluidity, microsphere water content,
      degree of methacrylate substitution, and type of dextran derivative used, on
      encapsulation efficiency, release, and integrity of the liposomes were
      investigated. RESULTS: Liposomes were entrapped in dextran-based microspheres
      quantitatively and with full preservation of their integrity. Liposomes with a
      low, as well as with a high membrane fluidity, were released from the
      microspheres in their intact form and with preservation of their size. Release
      kinetics depended only on the degradation rate of the microspheres. For rapidly
      degrading systems, pulsed release was observed and the time after which the pulse
      occurred (from 5 until 25 days) could be tailored by the gel characteristics such
      as initial water content, degree of methacrylate substitution, and type of
      hydrolytically sensitive spacer present in the cross-links. This delay time was
      not dependent on the size of the liposomes in the range studied (0.1-0.2 microm).
      Microspheres which degraded more slowly showed, after a certain delay time,
      sustained release of the liposomes extended up to 100 days. CONCLUSIONS: A novel
      drug delivery concept based on the encapsulation of liposomes in biodegradable
      dextran-based microspheres was designed. The system released the liposomes in
      intact form in a controlled way after a prolonged period of time.

PMID- 10955841
TI  - Preparation of biodegradable insulin nanocapsules from biocompatible
      microemulsions.
AB  - PURPOSE: To prepare poly(ethyl 2-cyanoacrylate) nanocapsules containing insulin
      by interfacial polymerization of spontaneously forming, biocompatible
      microemulsions. METHODS: A pseudo-ternary phase diagram of a mixture of medium
      chain glycerides (caprylic/capric triglycerides and mono-/diglycerides), a
      mixture of surfactants (polysorbate 80 and sorbitan mono-oleate) and water was
      constructed. Polarizing light microscopy was used to identify combinations
      forming microemulsions. Microemulsions were characterized by conductivity and
      viscosity to select systems suitable for the preparation of poly(ethyl 2
      cyanoacrylate) nanocapsules by interfacial polymerization. Nanocapsules were
      prepared by addition of 100 mg of ethyl 2-cyanoacrylate to a stirred water-in-oil
      microemulsion containing 1 g of water, 7.6 g of oil, and 1.4 g of surfactant. The
      nanocapsules formed were characterized by photon correlation spectroscopy, freeze
      fracture transmission and scanning electron microscopy. Insulin nanocapsules were
      prepared by using an aqueous solution of insulin (100 units/ml) as the dispersed
      phase of the microemulsion. The entrapment and the release of insulin from the
      nanocapsules were determined. RESULTS: Three regions were identified in the
      pseudo-ternary phase diagram; a microemulsion region, a region in which liquid
      crystalline structures were present and a coarse emulsion region. All systems in
      the microemulsion region were water-in-oil dispersions. Poly(ethyl 2
      cyanoacrylate) nanocapsules having a mean particle size of 150.9 nm were formed
      upon interfacial polymerization of the microemulsion. Nanocapsules were found to
      have a central cavity surrounded by a polymer wall. In excess of 80% of the
      insulin present in the microemulsion was encapsulated upon interfacial
      polymerization. CONCLUSIONS: Interfacial polymerization of spontaneously forming
      water-in-oil microemulsions represents a convenient method for the preparation of
      poly(alkylcyanoacrylate) nanocapsules suitable for the entrapment of bioactive
      peptides.

PMID- 10955843
TI  - An evaluation of the use of modulated temperature DSC as a means of assessing the
      relaxation behaviour of amorphous lactose.
AB  - PURPOSE: To evaluate the use of Modulated Temperature DSC (MTDSC) as a means of
      assessing the relaxation behaviour of amorphous lactose via measurement of the
      heat capacity, glass transition (Tg) and relaxation endotherm. METHODS: Samples
      of amorphous lactose were prepared by freeze drying. MTDSC was conducted using a
      TA Instruments 2920 MDSC using a heating rate of 2 degrees C/minute, a modulation
      amplitude of +/-0.3 degrees C and a period of 60 seconds. Samples were cycled by
      heating to 140 degrees C and cooling to a range of annealing temperatures between
      80 degrees C and 100 degrees C, followed by reheating through the Tg region.
      Systems were then recooled to allow for correction of the Tg shift effect.
      RESULTS: MTDSC enabled separation of the glass transition from the relaxation
      endotherm, thereby facilitating calculation of the relaxation time as a function
      of temperature. The relative merits of using MTDSC for the assessment of
      relaxation processes are discussed. In addition, the use of the fictive
      temperature rather than the experimentally derived Tg is outlined. CONCLUSIONS:
      MTDSC allows assessment of the glass transition temperature, the magnitude of the
      relaxation endotherm and the value of the heat capacity, thus facilitating
      calculation of relaxation times. Limitations identified with the approach include
      the slow scanning speed, the need for careful choice of experimental parameters
      and the Tg shift effect.

PMID- 10955844
TI  - Simultaneous determination of the heat and the quantity of vapor sorption using a
      novel microcalorimetric method.
AB  - PURPOSE: In this study, instrumentation for measuring vapor sorption enthalpies
      and sorption uptakes simultaneously with an isothermal microcalorimeter is
      introduced. Various pharmaceutical model substances undergoing phase transitions
      when exposed to humid conditions (25 degrees C), were employed to evaluate the
      usefulness and sensitivity of the constructed experimental method. METHODS: The
      sample is placed in the sample vessel of a RH cell and the moisture content of
      the air flow is controlled. From the RH cell the air flow is conducted into a
      subsequent perfusion cell in which a saturated salt solution has been loaded. The
      RH cell and perfusion cells are positioned in the sample sides of two twin
      calorimetric units. Depending on the moisture content in the outlet flow leaving
      the preceding RH cell, the heat flow signal from the subsequent perfusion cell
      will vary. By means of blank measurement with identical settings, the rate of
      water sorption can be calculated and, by integration, the amount of sorbed water
      is obtained. RESULTS: Amorphous lactose and cefadroxil undergo recrystallization
      when the moisture level in the surroundings exceeds the threshold values specific
      to each compound. During the sorption phase, heat is evolved fairly linearly as a
      function of consumed moisture, and also after the recrystallization, the heats
      indicate linear behavior. The heat values for the desorption phase of amorphous
      lactose and the adsorption of crystalline lactose coincide. With the different
      anhydrous forms of theophylline, the hydration takes place more rapidly in the
      metastable form 1, and generally, the process is more energetic in form 1. In all
      cases, the gravimetric results agree with the water sorption uptakes calculated
      from the calorimetric data. CONCLUSIONS: The technique introduced offers a rapid
      and sensitive method to gain new insights into the transitions in which vapors
      are involved. In addition, different kinds of surfaces with various energetics
      can now be studied more closely.

PMID- 10955845
TI  - Polyisobutylcyanoacrylate nanocapsules containing an aqueous core as a novel
      colloidal carrier for the delivery of oligonucleotides.
AB  - PURPOSE: The goal of the present paper was to encapsulate oligonucleotides in a
      new particulate carrier in order to protect them from enzymatic degradation.
      METHODS: Nanocapsules with an aqueous core containing oligonucleotides were
      prepared by interfacial polymerization of isobutylcyanoacrylate in a W/O
      emulsion. Ultracentrifugation and re-suspension in water yielded a dispersion of
      these containing an aqueous core nanocapsules. Zeta potential measurements and
      quenching of fluorescence of fluorescein-bounded oligonucleotides were used to
      study the localization of the oligonucleotides. Oligonucleotide degradation
      studies were carried out in fetal calf serum. RESULTS: Polydisperse nanocapsules
      of size ranging from 20 to 400 nm were obtained. Oligonucleotide loading did not
      significantly influence the zeta potential, suggesting they were located within
      the core of the nanocapsules. Fluorescence quenching assays confirmed this
      localization. When encapsulated in the nanocapsules and incubated in the presence
      of serum, the oligonucleotides were efficiently protected from degradation by
      nucleases, whereas oligonucleotides adsorbed onto nanospheres were protected less
      efficiently. CONCLUSIONS: This paper describes, for the first time, a
      nanotechnology able to encapsulate oligonucleotides rather than adsorbing them at
      the surface of a solid support. Such a formulation has great potential for
      oligonucleotide delivery.

PMID- 10955846
TI  - Synthesis and cytotoxic evaluation of a series of gamma-substituted gamma
      aryloxymethyl-alpha-methylene-gamma-butyrolactones against cancer cells.
AB  - PURPOSE: The main objective of this investigation was to explore the cytotoxic
      structure-activity relationships of gamma-substituted gamma-aryloxymethyl-alpha
      methylene-gamma-butyrolactones against cancer cells. METHODS: The target
      compounds were synthesized in two steps commencing with aryl-OH which was treated
      with a bromomethyl ketone followed by the Reformatsky-type condensation. RESULTS:
      Seven types of alpha-methylene-gamma-butyrolactones were evaluated in vitro
      against 60 human cancer cell lines derived from nine cancer cell types. The
      average values of log GI50 indicated that for the aryl portion, potencies of
      these alpha-methylene-gamma-butyrolactones are in a decreasing order of quinolin
      2(1H)-one (or 2-hydroxyquinoline, 21, -5.89) > quinoline (19, -5.79) > 2
      methylquinoline (20, -5.69) >8-hydroxyquinoline (17,-5.64) > 2-naphthalene (16, 
      5.59) > benzene (15, -4.90). The same order was obtained for both log TGI and log
      LC50. However, for the gamma-substituent, the potencies are in a decreasing order
      of biphenyl (16f-21f) > phenyl and 4-substituted phenyl (16b-e-21b-e) > methyl
      (16a-21a). CONCLUSIONS: Unlike cardiovascular activities of alpha-methylene-gamma
      butyrolactones in which a gamma-methyl substituent is necessary for vasorelaxing
      effect while a phenyl or a halogen-substituted phenyl is prefer for the
      antiplatelet activities, a gamma-biphenyl substituent proved to be the best for
      their cytotoxicities against various cancer cell lines tested.

PMID- 10955848
TI  - 2D and 3D QSAR analysis of some valproic acid metabolites and analogues as
      anticonvulsant agents.
AB  - PURPOSE: To investigate the structural features, responsible for the variations
      in anticonvulsant activity of a series of twenty six valproic acid (VPA)
      metabolites and analogues. METHODS: Different approaches for quantitative
      structure--activity relationship analysis (QSAR) as conventional 2D QSAR analysis
      and comparative molecular field analysis (3D QSAR) were used. The 2D QSAR was
      performed with more than twenty structure descriptors as the partition and
      distribution coefficients, topological, geometrical and electronic descriptors,
      and indicator variables. The electronic descriptors were calculated for the
      energetically most stable conformers. For the need of 3D QSAR steric and
      electrostatic potential maps were generated. Partial least squares (PLS) analysis
      has been carried out for the statistical evaluation of the models and weighted
      least squares (WLS) analysis was used for the visualization of the results.
      RESULTS: It was established that the two approaches--2D and 3D QSAR, prove the
      importance of the lipophilicity of the compounds for anticonvulsant activity. The
      results from both the approaches suggest that a substitution at alpha-position is
      essential for a higher activity. CONCLUSIONS: 3D QSAR is useful for describing
      the steric and electrostatic fields, important for the activity. For predicting
      the activity of new compounds 2D QSAR tools were proposed.

PMID- 10955847
TI  - Induction of T cell anergy by liposomes with incorporated major
      histocompatibility complex (MHC) II/peptide complexes.
AB  - PURPOSE: The aim of this study was to use small unilamellar liposomes with
      incorporated MHC II/peptide complexes as a carrier system for multivalent antigen
      presentation to CD4 + T cells. METHODS: Purified peptide pre-loaded MHC II
      molecules were incorporated into small unilamellar liposomes and tested for their
      ability to activate A2b T cells. The outcome of T cell activation by such
      liposomes in the absence of accessory cells was tested via flow cytometry and a T
      cell anergy assay. RESULTS: Provided the presence of external co-stimulation, MHC
      II/ peptide liposomes were able to induce proliferation of the A2b T cell clone.
      More importantly incubation of these T cells with MHC II/ peptide liposomes in
      the absence of co-stimulation did not induce proliferation, however, a
      MHC/peptide ligand-density dependent down-regulation of the TCR was observed.
      Interestingly, when T cells after incubation with the MHC II/peptide liposomes
      were restimulated with their specific antigen in the presence of professional
      APC, these cells were anergic. CONCLUSIONS: We propose MHC II/peptide liposomes
      as a novel means to induce T cell anergy. The possibility to prepare 'tailor
      made' liposomal formulations may provide liposomes with an important advantage
      for applications in immunotherapy.

PMID- 10955849
TI  - The effect of nasal patency on the clearance of radiolabeled saline in healthy
      volunteers.
AB  - PURPOSE: The objective of this study was to investigate the effect of nasal
      cavity patency on the penetration, deposition, and clearance of an aqueous
      isotonic saline solution. METHODS: The study was carried out as a single center,
      open, randomized, 2-way cross-over in healthy volunteers. Nasal patency was
      assessed using misting patterns on a cold metal surface at the beginning and end
      of study. 100 microl of technetium-99m radiolabeled saline solution was
      introduced into either the most or least patent nasal cavity using a purpose
      designed spray device. The distribution and residence time of the radiolabel was
      followed for 2 hours using gamma scintigraphy. RESULTS: The mean times to 50%
      clearance were 34+/-7 and 28+/-12 minutes (+/- s.d.) for the side view of the
      least and most patent nasal cavity respectively. Total clearance of the
      radiolabelled saline from the nose was not affected by patency. Between 7 and 35%
      of the radiolabelled saline solution remained in the nasal cavity at the end of
      imaging. Using endoscopy to track the clearance of an aqueous solution of food
      dye using the same delivery procedure, identified this region as hair in the
      nasal vestibule. The dye was seen to dry in this region along with the mucus.
      CONCLUSIONS: Nasal patency affects the initial, but not total clearance of
      solutions, however, the remaining solution may not be available for drug
      delivery.

PMID- 10955850
TI  - Transfer of dopamine in the olfactory pathway following nasal administration in
      mice.
AB  - PURPOSE: The aim of the study was to investigate whether dopamine is transferred
      along the olfactory pathway to the brain following nasal administration to mice.
      METHODS: [3H]-Dopamine was administered nasally or intravenously to female mice.
      Brain tissue samples were excised and the radioactive content was measured. The
      precise localisation of dopamine radioactivity in the brain was studied using
      autoradiography. The presence of dopamine or its metabolites in the olfactory
      bulb and mucosa was ascertained using thin layer chromatography (TLC). RESULTS:
      After administration of [3H]-dopamine into the right nostril, the amount of
      dopamine in the right bulb increased with time until. after 4 h, it was 27 times
      higher than in the left bulb. Among the other brain tissue samples, significantly
      higher amount of radioactivity was detected in the lateral olfactory tract.
      Radioactivity in the right olfactory bulb was shown by autoradiography to be
      selectively located in the peripheral layers 1 to 4 h after administration.
      Selective uptake of radioactivity was not seen in other regions of the brain. TLC
      data indicated that approximately 75% and 10% of the radioactivity in the
      olfactory bulb and mucosa, respectively, coeluted with dopamine. CONCLUSIONS: The
      results indicate that unchanged dopamine is transferred into the olfactory bulb
      following nasal administration of [3H]-dopamine.

PMID- 10955851
TI  - Biovector nanoparticles improve antinociceptive efficacy of nasal morphine.
AB  - PURPOSE: We have studied the antinociceptive activity and blood and brain
      delivery of nasal morphine with or without Biovector nanoparticles in mice.
      METHODS: A tail flick assay was used to evaluate the antinociceptive activity.
      The kinetics of morphine were evaluated in blood and brain, using tritiated
      morphine as tracer. RESULTS: These nanoparticles were shown to increase the
      duration of the antinociceptive activity of morphine after nasal administration.
      This effect was not due to an increase of morphine in the blood; and the
      analgesic activity of morphine in association with nanoparticles was reversed by
      naloxone. The ED50 value was 33.6+/-15.6 mg/kg for morphine alone and 14.4+/-7.6
      mg/kg in presence of nanoparticles. They were only effective at low doses (1.5 to
      2.5 microg), a higher or a lower dose had no effect. No interaction was found
      between nanoparticles and morphine. NaDOC, a permeation enhancer, was unable to
      improve nasal morphine activity. CONCLUSIONS: These results show the presence of
      nanoparticles only at a very specific dose increases the antinociceptive activity
      of nasal morphine in mice. The occurrence of a direct transport of morphine from
      the nasal mucosa to the brain is discussed.

PMID- 10955853
TI  - Permeation studies in vitro and in vivo of potential radiopharmaceuticals with
      affinity to neuro receptors.
AB  - PURPOSE: To check the influence of structural characteristics on their permeation
      through the blood-brain barrier (BBB), a set of radioactive [99mTc]chelates
      bearing amine groups was synthesized and tested in vitro as well as in vivo.
      METHODS: Compounds with different log P and pKa values were obtained by complex
      forming reactions of [99mTc]pertechnetate with varying substituents. Transport
      was studied in rats and mice, as well as in an ECV304 cell culture model.
      RESULTS: In vitro higher permeation was found for compounds with electron
      attracting substituents in beta-position to the amine group (pKa values 7.4 to
      8.3) than for those with more basic amine groups (pKa values > 8.9) even for
      similar log DH 7.4. In vivo brain uptake between 0.8 and 4.8% of the injected
      dose (ID) per organ was found for the former, whereas <0.4% ID were present for
      the latter. CONCLUSIONS: Three structurally diverse classes of [99mTc]chelates
      showed distinct patterns with regard to brain uptake in vivo and BBB permeability
      in vitro which could not be predicted by their lipophilicity alone. The close
      correlation between the data from rats and mice and those obtained with cell
      cultures render the ECV304 cells an attractive model for the screening of new
      compounds.

PMID- 10955852
TI  - Morphine antinociception is enhanced in mdr1a gene-deficient mice.
AB  - PURPOSE: Previous studies have suggested that P-glycoprotein (P-gp) modulates
      opioid antinociception for selected mu-and delta-agonists. This study was
      undertaken to assess morphine antinociception in mice lacking the mdr1a gene for
      expression of P-gp in the CNS. METHODS: Morphine (n = 4-5/group) was administered
      as a single s.c. dose to mdr1a(-/-) mice (3-5 mg/kg) or wild-type FVB controls (8
      10 mg/kg). Tail-flick response to radiant heat, expressed as percent of maximum
      response (%MPR), was used to determine the antinociceptive effect of morphine.
      Concentrations in serum, brain tissue, and spinal cord samples obtained
      immediately after the tail-flick test were determined by HPLC with fluorescence
      detection. Parallel experiments with R(+)-verapamil, a chemical inhibitor of P
      gp, also were performed to further investigate the effect of P-gp on morphine
      associated antinociception. RESULTS: Morphine-associated antinociception was
      increased significantly in the mdr1a(-/-) mice. The ED50 for morphine was > 2
      fold lower in mdr1a(-/-) (3.8+/-0.2 mg/kg) compared to FVB (8.8+/-0.2 mg/kg)
      mice. However, the EC50 derived from the brain tissue was similar between the two
      mouse strains (295 ng/g vs. 371 ng/g). Pretreatment with R(+)-verapamil produced
      changes similar to those observed in gene-deficient mice. P-gp does not appear to
      affect morphine distribution between spinal cord and blood, as the spinal
      cord:serum morphine concentration ratio was similar between gene-deficient and
      wild-type mice (0.47+/-0.03 vs. 0.56+/-0.04, p>0.05). CONCLUSIONS: The results of
      this study are consistent with the hypothesis that P-gp attenuates the
      antinociceptive action of morphine by limiting the brain:blood partitioning of
      the opioid.

PMID- 10955854
TI  - Carrier-mediated transport of macrolide antimicrobial agents across Caco-2 cell
      monolayers.

PMID- 10955855
TI  - Elevation of plasma prolactin in patients undergoing autologous blood stem-cell
      transplantation for breast cancer: is its modulation a step toward posttransplant
      immunotherapy?
AB  - Prolactin is a suspected promotor of breast cancer cell growth, and it shares
      pleiotropic immunoregulatory properties. We studied plasma prolactin and its drug
      induced modulation in 20 women with breast cancer undergoing high-dose
      chemotherapy and autologous blood stem-cell transplantation. Plasma prolactin
      levels were serially assayed before and during conditioning and within and beyond
      30 days after transplant. Before transplant, prolactin plasma levels were in the
      age-adjusted range of normal women. During conditioning and within 30 days after
      transplant, prolactin levels increased in all patients (p < 0.0001), but remained
      in the normal range. Antiemetic drugs such as metoclopramide and phenothiazines,
      known to enhance pituitary prolactin secretion, further elevated prolactin plasma
      levels (p < 0.00001). Patients remaining in continuous complete remission after
      transplant (median follow-up, 3 years) disclosed higher prolactin levels compared
      with those obtaining only partial remission or ensuing early relapse. Prolactin
      levels are regularly elevated during conditioning and within 30 days after
      autologous transplantation for breast cancer. Further elevations of prolactin
      plasma levels are induced by metoclopramide and other antiemetic drugs. Elevated
      plasma prolactin had no adverse effect on disease-free survival after transplant.
      We propose to investigate further the upregulation of prolactin after transplant
      aiming to induce a posttransplant consolidative immune reaction.

PMID- 10955856
TI  - Potency preservation after three-dimensional conformal radiotherapy for prostate
      cancer: preliminary results.
AB  - We sought to assess potency preservation after three-dimensional conformal
      radiotherapy (3D-CRT) in prostate cancer patients eligible for radical
      prostatectomy, conventional radiotherapy, 3D-CRT, or transperineal prostate
      implantation. Patients with more advanced disease are commonly treated with
      hormonal therapy, which can cause impotence, and were consequently excluded from
      the analysis. Between December 1991 and June 1998, 198 prostate cancer patients
      were treated with 3D-CRT at the University of California, Davis Medical Center.
      Fifty-two of these patients had a pretreatment prostate-specific antigen (PSA)
      level of 10.0 ng/ml or less, a Gleason score of 6 or less, and a 1997 AJCC
      clinical stage T1bN0M0 to T2bN0M0. One patient was not evaluable. None of the 51
      evaluable patients had diabetes mellitus. In 40 patients, the prostate gland only
      was irradiated to a total dose of 66 to 79.2 Gy by using daily 1.8-Gy fractions.
      In 11 patients, the prostate and seminal vesicles were treated to 44 to 55.8 Gy.
      Lymph nodes were not included in the clinical target volume. The median age was
      68 years, and the median length of follow-up was 15 months. Potency in this study
      is defined as an erection sufficient for vaginal penetration. Kaplan-Meier
      analysis was used to describe potency as a function of time after 3D-CRT. Of the
      51 evaluable patients, 35 (69%) were potent, 15 were impotent, and 1 was sexually
      inactive before 3D-CRT. Kaplan-Meier estimates of the potency preservation rates
      1, 2, and 3 years after 3D-CRT are 100%, 83%, and 63%, respectively. On
      multivariate analysis, age, total radiation dose, and a history of transurethral
      resection of the prostate did not significantly affect potency preservation
      rates. Three (43%) of 7 patients who became impotent after 3D-CRT and used
      sildenafil were subsequently able to achieve erections sufficient for vaginal
      penetration. The preliminary results reported herein suggest that approximately
      two thirds of prostate cancer patients will retain their potency 3 years after 3D
      CRT. Further follow-up is necessary to assess long-term potency after 3D-CRT.
      Sildenafil should be considered in patients who develop radiation-induced
      impotence.

PMID- 10955857
TI  - Treatment of prognosis of primary breast lymphoma: a review of 13 cases.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the breast is a rare entity that does not
      have a well-defined treatment strategy. At presentation, most patients are
      clinically thought to have a primary breast carcinoma, and the diagnosis of
      lymphoma is made at biopsy. Once the diagnosis of lymphoma is made, patients are
      treated with some combination of chemotherapy, radiation therapy, and surgery. We
      review The Cleveland Clinic Foundation experience with primary breast lymphoma.
      Between 1980 and 1996, 17 patients with primary breast lymphoma were seen at The
      Cleveland Clinic Foundation, and 13 had follow-up information available. All
      patients underwent a staging workup including computed tomography (CT) scan of
      the chest, abdomen, and pelvis, as well as bilateral bone marrow biopsies; all
      patients staged IE (breast involvement only) or IIE (limited to the breast and
      ipsilateral axilla) were included. We did not include patients with more
      extensive supradiaphragmatic nodal involvement who were stage IIE. Patients
      received some combination of surgery, radiation, and chemotherapy. The median
      follow-up was 34 months, with a range of 7 to 138 months. There was an equal
      incidence of right- versus left-sided lesions. Five patients survived at least 5
      years from the time of diagnosis. Long-term survival in patients with primary NHL
      of the breast is possible. We recommend treating patients with aggressive NHL of
      the breast with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
      chemotherapy, followed by involved field radiation and treating those patients
      with indolent lymphoma with involved field radiation alone.

PMID- 10955858
TI  - Large-field, external beam irradiation as a surgical adjuvant for node-positive
      colon carcinoma: an Eastern Cooperative Oncology Group Pilot Study (PA285).
AB  - The Eastern Cooperative Oncology Group (ECOG) PA-285 study was designed as a
      pilot study to evaluate the effect of large-field, external beam abdominal
      irradiation as an adjuvant treatment for resectable stage C1 to C2 colon cancer.
      Eligible patients received 45 Gy directed to the tumor bed and periaortic lymph
      nodes, as well as 30 Gy to the liver. Patients were followed up for time to
      recurrence and for survival. Fourteen patients were enrolled. One elected not to
      have radiation after surgery; one died of acute hepatic radiation toxicity after
      a major deviation from protocol. Of the 12 remaining patients, seven survived
      longer than 10 years for a survival rate of 58%. Other than the fatal hepatic
      toxicity, side effects from radiation were moderate and of short duration. One
      patient failed to complete therapy because of ascites, had two episodes of
      partial bowel obstruction (successfully treated conservatively), and subsequently
      survived more than 10 years. Two of three patients with stage C1 tumors, four of
      eight with C2 tumors, and one with a C3 tumor were long-term survivors. This
      study demonstrates the feasibility and acceptable toxicity of this adjuvant
      regimen. The numbers are too limited to evaluate survival, but all seven
      survivors have lived more than 10 years.

PMID- 10955859
TI  - Frontline treatment of advanced gastric cancer with docetaxel and granulocyte
      colony-stimulating factor (G-CSF): a phase II trial.
AB  - We conducted a phase II study to evaluate the efficacy and tolerance of docetaxel
      monotherapy with granulocyte colony-stimulating factor (G-CSF) support in
      patients with advanced gastric cancer. Thirty patients with measurable advanced
      gastric cancer were enrolled. Twenty-four patients were chemotherapy-naive and
      six patients had previously received adjuvant chemotherapy after complete
      surgical resection. Docetaxel was administered at 100 mg/m2 IV during 1 hour
      every 3 weeks. G-CSF 5 microg/kg SC was also given on days 2 through 8
      prophylactically to all patients. All patients were evaluable for response and
      toxicity. We observed one complete and five partial responses for an overall
      response rate of 20% (95% confidence interval: 6-34%). In addition, seven
      patients (23%) had stable disease. After a median follow-up time of 7 months, the
      median duration of response was 4.5 months, the median time of tumor progression
      was 6 months, and the median survival was 7 months. The estimated probability of
      1-year survival was 28%. Toxicity was generally mild. Grade III/IV neutropenia
      occurred in 11 (36%) patients. Neutropenia with fever developed in three patients
      (10%). There were no toxic deaths. Docetaxel with G-CSF support is an active drug
      and well tolerated by patients with advanced gastric cancer. Docetaxel merits
      further investigation in combination with other active agents as frontline
      treatment in patients with advanced gastric cancer.

PMID- 10955860
TI  - Correlation of radiation tolerance dose of normal human organs with organ weight,
      blood, and water content.
AB  - The concerted effort to minimize the radiation exposure to normal human tissues
      while delivering a high radiation dose to the tumor often results in
      complications. This limits the efficacy of radiation treatment. Analysis of
      radiation tolerance dose with organ weight in 15 human organs yields a
      correlation coefficient of 0.62, whereas the correlation of radiation tolerance
      dose with blood and water content yields correlation coefficients of 0.82 and
      0.60, respectively. Results indicate that as the organ weight and/or blood and
      water content increases, radiation tolerance dose decreases.

PMID- 10955861
TI  - Phase I study of paclitaxel and day 1/day 8 gemcitabine in patients with solid
      malignancies.
AB  - A phase I study was designed to evaluate the toxicity of escalating doses of
      gemcitabine along with fixed-dose paclitaxel in patients heavily pretreated with
      chemotherapy or radiotherapy. All patients had no prior therapy with the study
      drugs and possessed both adequate performance and end organ function. Eighteen
      patients were entered in the study. Characteristics included a median age of 66
      years (range, 41 to 77) and stage IV disease in all patients; there were six
      patients with colon cancer, two with bladder cancer, three with non-small-cell
      lung cancer, two with esophageal cancer, three with pancreatic cancer, and two
      with cancer of unknown primary. Paclitaxel (150 mg/m2 over 3 hours) was given on
      day 1 and gemcitabine (800, 900, and 1,000 mg/m2 over 15 minutes) was given in
      three separate dose-escalating cohorts (1-3) on days 1 and 8. The treatment
      cycled every 21 days. The dose-limiting toxicity (DLT) proved to be neutropenia.
      All nonhematologic toxicities were mild and included gastrointestinal (nausea,
      vomiting, and diarrhea), dermatologic (rash), and neurologic (paresthesias)
      disturbances along with transient elevations of liver function tests. The
      combination of gemcitabine and paclitaxel seems to be well tolerated, and the
      recommended starting dose for a phase II study, in pretreated patients using a
      day 1/day 8 treatment schedule, should be 900 mg/m2 for gemcitabine (days 1 and
      8) along with 150 mg/m2 for paclitaxel (day 1).

PMID- 10955862
TI  - Mesenteric venous thrombosis attributed to docetaxel.
AB  - We present a case of a 57-year-old woman with metastatic breast cancer
      unresponsive to several chemotherapeutic and hormonal regimens. Because of
      progressive pulmonary metastases and a painful osteolytic metastasis in the
      sternum, treatment with docetaxel was initiated. She developed mesenteric venous
      thrombosis within 1 week after the first dose of docetaxel. Although docetaxel
      may be regarded as an important advancement in the chemotherapeutic treatment of
      several cancers, ongoing and future trials must assess its position in the
      standard chemotherapeutic treatment of cancer. Well-documented adverse reactions,
      either common or rare, may contribute to a balanced risk-benefit profile of
      docetaxel.

PMID- 10955863
TI  - Phase II trial of topotecan in patients with advanced, persistent, or recurrent
      uterine leiomyosarcomas: a Gynecologic Oncology Group Study.
AB  - From October 1995 to March 1997, a phase II trial of topotecan was carried out in
      chemotherapy-naive women with advanced, persistent, or recurrent uterine
      leiomyosarcomas. Thirty-six patients were entered. Median age was 53 years.
      Performance status was 0 (50%) in 18, 1 (36%) in 13, and 2 (14%) in 5. Most
      patients, 33 (92%), had undergone prior surgery, and 8 (22%) prior radiation
      therapy. Topotecan, 1.5 mg/m2. was administered intravenously daily for 5 days,
      every 3 weeks, until progression of disease or adverse affects prohibited further
      therapy. Patients received 1 to 13 courses with a median of 3 courses. The most
      frequent grade 4 adverse effects were neutropenia in 28 (78%), leukopenia in 8
      (22%), thrombocytopenia in 3 (8%), and anemia in 3 (8%). Complete response was
      seen in 1 (3%), partial response in 3 (8%), stable disease in 12 (33%), and
      increasing tumor in 20 (56%). Thus topotecan at this dose and schedule does not
      appear to have major activity in uterine leiomyosarcomas.

PMID- 10955864
TI  - Pharmacokinetics of ifosfamide are changed by combination with docetaxel: results
      of a phase I pharmacologic study.
AB  - The pharmacokinetics of the combination of docetaxel and ifosfamide were studied
      in a phase I study. Docetaxel was given to cancer patients as a 1-hour infusion
      followed by a 24-hour infusion of ifosfamide (schedule A). After the dose
      limiting toxicity of the combination was reached, ifosfamide was administered as
      a 24-hour infusion followed after 24 hours by a 1-hour infusion of docetaxel
      (schedule B). Cycle duration was 21 days. Docetaxel was determined by high
      performance liquid chromatography, and ifosfamide and its metabolites, by gas
      chromatography-mass spectrometry. Twenty-seven patients were treated according to
      schedule A, and 6 according to schedule B. Combining the two drugs did not change
      their respective plasma half-lives. The sequence of drug administration did not
      affect the clearance and the area under the curve (AUC) of docetaxel. There was a
      decrease in the AUC of ifosfamide in schedule A compared with schedule B,
      resulting from an increase in the clearance of ifosfamide. The pharmacokinetics
      of docetaxel are not influenced by combination with ifosfamide, regardless of the
      drug sequence, but ifosfamide pharmacokinetics are changed by docetaxel,
      depending on the sequence of administration. The increase of clearance in
      schedule A may be due to the pretreatment with corticosteroids.

PMID- 10955865
TI  - Multiple primary neoplasms at a single institution: differences between
      synchronous and metachronous neoplasms.
AB  - During the 10-year period (1987-1996) of our study, 26,255 patients with cancer
      were admitted to our clinic and, of these, 271 (1%) patients had multiple primary
      malignant tumors. Ninety-two (34%) patients had synchronous tumors (synchronous
      group), and 179 (66%) patients had metachronous tumors (metachronous group). The
      mean age at first diagnosis was higher in the former group. The ratio of men to
      women was 1.36 in the synchronous group and 0.74 in the metachronous group (p =
      0.018). Smokers and drinkers were more common in the synchronous group. Breast
      cancer and lung cancer were most prevalent, and associations between head/neck
      and lung cancer and between breast and breast cancer were the most frequent
      associations in both the synchronous and the metachronous group. The frequency of
      aerodigestive tumors was higher and that of mesenchymal tumors was lower in the
      synchronous group than in the metachronous group. Localization in the medial
      region and in the head/neck was more frequent in the synchronous group than in
      the case of metachronous secondary tumors.

PMID- 10955866
TI  - Phase II trial of cisplatin, etoposide, and 5-fluorouracil in advanced non-small
      cell lung cancer: an Eastern Cooperative Oncology Group Study (PB586).
AB  - Advanced non-small-cell lung cancer (NSCLC) remains an incurable disease despite
      significant progress in chemotherapy. We conducted a phase II clinical trial to
      investigate the efficacy and toxicity of a cisplatin, etoposide, and 5
      fluorouracil (5-FU) combination in advanced metastatic and/or recurrent NSCLC.
      Forty patients with advanced, recurrent, or metastatic, measurable NSCLC were
      treated with cisplatin, 60 mg/m2 intravenously (i.v.) on day 1; etoposide, 120
      mg/m2/day i.v. on days 1, 2, and 3; and 5-FU. 1,000 mg/m2/day i.v. continuous
      infusion on days 1 through 5. Treatment was administered in 4-week cycles. Thirty
      patients had distant metastases and were previously untreated, and 10 patients
      had recurrent disease after prior treatment with either surgery (1 patient),
      radiation therapy (5 patients), or both treatments (4 patients). Twenty-nine
      patients were evaluable for response. Seven (24%) patients achieved a partial
      remission (PR), 18 (62%) had stable disease (SD), and 8 (14%) had progressive
      disease (PD). Overall median survival was 7.9 months (range, 0.4-27.4 months).
      Patients who achieved a PR had a median survival of 23.5 months (9.3-27.4
      months). In contrast, patients with SD had a median survival of 9.9 months (2.5
      25.3 months), and patients with PD had a median survival of 2.1 months (1-9.3
      months). Median duration of response of 27.1 weeks (4.9-76.5 weeks) for patients
      with PR, and time to progression was 13.4 weeks (3.7-54.5 weeks) for patients
      with SD. Toxicity was primarily hematologic and gastrointestinal, and there were
      three deaths due to infection. The combination of cisplatin, 5-FU, and etoposide
      as administered in this study appears to have considerable toxicity and does not
      appear to be superior to other cisplatin-containing regimens used for the
      treatment of advanced NSCLC.

PMID- 10955867
TI  - Desmoid tumors in a woman with idiopathic multicentric osteolysis: result of
      three etiologic factors or coincidence?
AB  - Desmoid tumors developed on the toes of a young woman with idiopathic
      multicentric osteolysis (IMO) after amputation of the toenails. A summary of IMO
      is given, and a review of literature for the etiologic factors of desmoid tumors
      is added.

PMID- 10955868
TI  - Phase II trial of menogaril in patients with previously treated multiple myeloma
      or chronic lymphocytic leukemia.
AB  - Menogaril is a semisynthetic anthracycline with relative lack of cardiotoxicity.
      Ten patients with multiple myeloma (MM), seven patients with chronic lymphocytic
      leukemia (CLL), and one patient with diffuse well-differentiated lymphocytic
      lymphoma (DWDL) were treated with menogaril, 160 mg/m2 (for MM) or 200 mg/m2 (for
      CLL/DWDL), given as a 2-hour intravenous infusion, repeated every 28 days. All
      patients except one with CLL had been previously treated with one chemotherapy
      regimen and had either not responded or had relapsed after a response to prior
      treatment. There were no objective responses to treatment. Among the six
      evaluable patients with MM, two had stable disease with subjective improvement in
      symptoms for five to 25 cycles, and among the eight patients with CLL/DWDL, five
      patients remained stable for two to eight cycles on treatment. The remainder of
      the patients had progressive disease after one to two cycles of chemotherapy.
      Five grade 4 hematologic toxicities were observed. There was one fatal
      neutropenic sepsis. Menogaril, as administered in this study, does not appear to
      have significant activity in patients with previously treated MM or CLL.

PMID- 10955869
TI  - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with
      prostatic carcinoma.
AB  - Inappropriate antidiuretic hormone secretion (SIADH) may occur in a variety of
      diseases, including malignancies, and can be induced by drugs. We report a case
      of SIADH associated with prostatic carcinoma. A 50-year-old man was admitted to
      hospital with severe flank pain and weight loss. The diagnosis of SIADH syndrome
      and prostatic carcinoma was established, and hormonal therapy was instituted.
      However, the patient died in a month without any response to therapy. We conclude
      that prostatic carcinoma may cause SIADH and should therefore be considered in
      the differential diagnosis.

PMID- 10955870
TI  - Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in
      patients with obstructive esophageal cancer.
AB  - Obstructing esophageal cancer produces severe dysphagia with ensuing death within
      90 days. Palliation is possible with modalities like stent placement, laser, and
      photodynamic therapy. However, these treatments have a high rate of
      complications, and the overall mortality is not altered. A new alternative
      treatment evaluated in this study is endoscopic intratumoral injection with
      cisplatin/epinephrine (CDDP/epi) gel. CDDP/epi gel injections were administered
      weekly for 3 to 8 weeks in nine patients, median age, 72 years; mean tumor volume
      (+/-SEM), 41.44 (+/-22.4) cm3. Eight patients had stage IV, and one had stage III
      esophageal carcinoma. The mean dysphagia score (+/-SEM) was 3.5 (+/-0.17). All
      patients were followed up until death. Dysphagia resolved in eight patients with
      reduction in mean dysphagia score (+/-SEM) from 3.5 (+/-0.17) to 0.75 (+/-0.28; p
      = 0.005). Tumor volume was reduced by 75% in one patient and by 50% in two
      patients. The median survival was 4 months. The longest follow-up has been 15
      months (458 days). In this pilot study, intratumoral injection of CDDP/epi gel
      restored swallowing in eight of nine patients and was an effective and safe
      outpatient treatment in patients with obstructive esophageal cancer.

PMID- 10955872
TI  - Optic nerve sheath fenestration for a reversible optic neuropathy in radiation
      oncology.
AB  - To the authors' knowledge, there is a paucity of published accounts of management
      of radiation-induced optic neuropathy (RION) by optic nerve sheath fenestration
      (ONSF) in the conventional medical literature. With higher doses of radiation
      being given by using conformal techniques, more radiation-induced optic neuritis
      and neuropathy will be identified. We report here the successful use of ONSF to
      restore vision to three consecutive patients with pending anterior RION, and the
      importance of early identification and intervention in these potentially
      reversible cases.

PMID- 10955871
TI  - Lenograstim as support for ACE chemotherapy of small-cell lung cancer: a phase
      III, multicenter, randomized study.
AB  - This phase III study was conducted to evaluate the usefulness of lenograstim as
      support for ACE (doxorubicin, cyclophosphamide, and etoposide) chemotherapy in
      previously untreated patients with small-cell lung cancer. Patients were
      randomized to receive up to six 3-week cycles of either ACE alone (n = 139) or
      ACE with lenograstim support (150 microg/m2/day subcutaneously, days 4-13, n =
      141). Compared with the chemotherapy-alone group, the lenograstim support group
      was more likely to achieve neutrophil recovery (absolute neutrophil count, > or
      =1.5 x 10(9) cells/l) by day 14 (95.8-100% vs. 14.3-24.1% across the cycles) and
      less likely to experience at least one infectious episode (36.7 vs. 54.0%; p =
      0.004), chemotherapy delay (51.8 vs. 56.2%; NS), or dose reduction (17.3 vs.
      27.7%; p = 0.037). Objective response and event-free and overall survival rates
      were similar. Lenograstim was well tolerated. Lenograstim may allow the interval
      between cycles of ACE to be reduced to 2 weeks; such dose intensification may
      lead to more favorable objective response and survival rates.

PMID- 10955873
TI  - Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy
      and autologous peripheral blood stem cell transplantation.
AB  - In an attempt to limit toxicities associated with dose-intensive therapy used for
      transplant regimens, we performed a pilot study using amifostine with high-dose
      busulfan (12 mg/kg), melphalan (100 mg/m2), and thiotepa (500 mg/m2) in 21
      patients with a variety of malignancies. After 3 days of oral busulfan,
      amifostine was given at 910 mg/m2 IV for 10 minutes, preceding the infusion of
      each of 2 doses of melphalan and thiotepa given for 4 days. Antiemetic
      premedication for amifostine was given to all patients. The median patient age
      was 50 years (range: 32-65 years). Twenty-one patients received 82 separate
      amifostine infusions. One patient discontinued amifostine after the second dose
      because of severe nausea and emesis, and two infusions were temporarily held
      secondary to hypotension. Of these 82 cycles, there was a total of 37 episodes of
      nausea/vomiting, 28 episodes of sneezing, 11 episodes of flushing, and 1 episode
      of oral paresthesia. Systolic blood pressure and mean arterial pressure decreased
      by a mean of 8.4 mm Hg and 5.0 mm Hg, respectively. In general, the infusion was
      well tolerated. Patients were observed until discharge home (N = 15), until
      initiation of an additional tandem transplant procedure (N = 4), or until death
      (N = 2). All twenty-one patients experienced nonhematologic toxicities grade II
      or greater. Grade II toxicities included mucositis (N = 21), gastrointestinal (N
      = 3), skin (N = 1), and liver (N = 1), and grade III toxicities included liver (N
      = 1). Mucositis was also scored according to a detailed toxicity assessment.
      Mucositis did not appear to be improved with amifostine when compared with a
      control group of patients not receiving amifostine. Renal dysfunction after
      transplantation was decreased in the amifostine group, whereas there was no
      significant effect on posttransplant hepatic dysfunction. Although these data
      demonstrate the feasibility of delivering parenteral amifostine in conjunction
      with dose-intensive chemotherapy and autologous peripheral blood stem cell
      transplantation, there was no evidence of a significant reduction in nonmarrow
      toxicities.

PMID- 10955875
TI  - Epithelial ovarian cancer presenting initially with extraabdominal or
      intrahepatic metastases: a preliminary report of 25 cases and literature review.
AB  - The purpose of this study was to investigate the clinical features of patients
      with epithelial ovarian cancer (EOC) that are initially categorized as
      extraabdominal adenocarcinoma of unknown primary. Twenty-five patients with EOC,
      who were treated in the Cancer Hospital of Shanghai Medical University from
      January 1986 to December 1997, and manifesting as extraperitoneal or liver
      parenchyma metastases at the time of presentation without detectable ovarian
      tumors, were retrospectively studied. Sixteen patients (64%) were optimally
      surgical debulked. When compared with 52 other women with stage IV EOC, 20
      patients who initially sought treatment for extraabdominal metastases experienced
      a better prognosis, with an estimated median survival of 24 months versus 10
      months (p = 0.0427). The median survival was 30 months in patients with pleural
      effusion or supraclavicular lymph node metastases versus 19 months in those with
      spread to other sites (p = 0.0264). The prognosis of such cases, mainly for those
      with supraclavicular lymphadenopathy or malignant pleural effusion, is better
      than that for other stage IV EOC patients, probably because most of the patients
      who initially had distant metastases were generally in condition that permitted
      aggressive surgery or multicycle chemotherapy.

PMID- 10955874
TI  - Long-acting depot lanreotide in the treatment of patients with advanced
      neuroendocrine tumors.
AB  - Long-acting depot forms of somatostatin analogs administered by intramuscular
      injections are now available for the treatment of neuroendocrine tumors (NETs).
      In the present study, we investigated the efficacy and tolerability of a slow
      release form of lanreotide in patients with advanced NETs. From July 1996 to
      January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine
      pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated
      with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization.
      All the patients had measurable disease. Seventeen patients were symptomatic and
      20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was
      positive in 23 of 25 patients. Lanreotide was administered as intramuscular
      injections at the dose of 30 mg every 2 weeks until there was objective,
      biochemical, or symptomatic tumor progression. Objective partial responses (PRs)
      were documented in 2 patients (8%), whereas 10 patients (40%) had tumor
      stabilization. The PRs were observed in patients with midgut carcinoids, of whom
      one was pretreated with subcutaneous octreotide. The response duration was 21+
      and 24+ months in responding patients; the median duration of disease
      stabilization was 8.5 months (range, 4-21+). The overall biochemical response
      rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all
      biochemical responses were observed mostly in patients with carcinoid tumors; the
      duration of response was 18+ and 30+ months for CRs; the median duration of
      biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic
      response rate was 70% with a median duration of 7.5, 18, and 18+ months for
      diarrhea, abdominal pain, and flushing, respectively. Median duration of
      lanreotide treatment was 10 months (range, 2-30+). No significant side effects
      were reported. Depot lanreotide 30 mg shows significant efficacy in terms of
      objective response rate and in biochemical and symptomatic control, in pretreated
      patients as well as nonpretreated patients with advanced NETs. Tolerability is
      good, with good patient compliance.

PMID- 10955876
TI  - Cisplatin, cytarabine, caffeine, and continuously infused 5-fluorouracil (PACE)
      in the treatment of advanced pancreatic carcinoma: a phase II study.
AB  - Encouraging results using cisplatin, cytarabine, and caffeine for the treatment
      of pancreatic carcinoma prompted a phase II study using these agents and adding
      continuous intravenous infusion (CI) 5-fluorouracil (5-FU) (PACE). Patients with
      advanced pancreatic adenocarcinoma who had not received prior cytotoxic therapy
      were eligible. Treatment consisted of the following: on day 1, the administration
      of cisplatin 100 mg/m2 IV, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and
      caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and on days 3 to
      21, 5-FU 250 mg/m2/day given by CI. Cycles were repeated every 28 days. Thirty
      eligible patients were entered in the study. The median number of cycles received
      was three. Grade IV neutropenia and thrombocytopenia occurred in 53% and 27% of
      patients, respectively. Among 30 treated patients, complete remission (CR) was
      seen in 2 patients and partial remission (PR) in 3 patients, for an overall
      response rate of 16.7% (95% confidence interval 6.8-32.4%). The median survival
      was 5.0 months (range: 0.3-32.4 months) and 16.7% and 10% of patients were alive
      at 1 and 2 years. respectively. Changes in the serum level of CA 19-9 provided an
      early marker of response which translated in differences in survival. Those with
      increasing or decreasing/stable levels of CA 19-9 after the first cycle of
      therapy had median survivals of 1.7 and 8.3 months, respectively (p = 0.0002).
      Although PACE chemotherapy produced durable responses in pancreatic cancer, the
      toxicity was substantial. A modification of this regimen with newer, less toxic
      drugs may provide better results and reduced toxicity. Also, the monitoring of
      the serum CA 19-9 level may provide a means to assess response and predict
      survival.

PMID- 10955877
TI  - Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary
      tract adenocarcinomas.
AB  - Adenocarcinomas of the pancreas and biliary tract are highly malignant neoplasms,
      which are found in the advanced stage. Chemotherapy commonly plays a palliative
      role in the treatment of pancreatic and biliary tract cancers. 5-Fluorouracil (5
      FU) is the most widely studied single agent; the response rate of 5-FU is only
      20%. Recently, some reports presented interesting results, in which 5-FU,
      modulated with levofolinic acid (leucovorin), was active in patients with
      colorectal cancer. In relation, we performed a phase II study of 5-FU, modulated
      with leucovorin, in patients affected by advanced pancreatic or biliary tract
      cancer. Fifty-one patients with nonresectable carcinomas of the pancreas or
      biliary tract admitted to Korea University Hospital between May 1995 and December
      1998 were included in this study. Chemotherapy consisted of leucovorin 25
      mg/m2/day by 2-hour intravenous infusion, followed by 5-FU 375 mg/m2/day by bolus
      intravenous infusion, from day I to day 5. The treatment was repeated every 3 to
      4 weeks. A total of 51 eligible patients with advanced adenocarcinoma of the
      pancreas or biliary tract were enrolled. Of 23 enrolled patients with pancreatic
      adenocarcinoma, one patient showed complete remission with a survival duration of
      13 months (response duration was 9 months). Three patients had partial responses
      (PRs) with survival times of 6, 12, and 15 months, respectively. The overall
      response rate was 17.4% (95% confidence interval [CI], 7.2%-36.2%). The median
      time of overall survival was 6 months (range: 1-15 months). Of 28 enrolled
      patients with biliary tract cancer, complete responses were observed in 2
      patients (7.1%) with survival time of 14 and 16 months, respectively. Seven
      patients had PRs with a median survival of 8 months. The overall response rate
      was 32.1% (95% CI, 20.3%-57.5%). The median time of overall survival was 6 months
      (range: 1-16 months). The most prominent toxicity was mucositis. Hematologic
      toxicity was less severe. 5-Fluorouracil in modulation with intravenous
      leucovorin is well tolerated by patients with stage IV pancreatic adenocarcinoma
      or biliary tract cancer. Although the response rate for patients with pancreatic
      adenocarcinoma is not better than that achieved using 5-FU monochemotherapy, the
      32.1% overall response rate achieved in patients with biliary tract cancer
      suggests that 5-FU modulation with leucovorin is active in biliary tract cancer.

PMID- 10955878
TI  - Primary osteosarcoma of metatarsal bone.
AB  - Primary osteosarcomas of the short tubular bones of hands and feet are rare. We
      describe a 46-year-old woman with osteosarcoma of the left metatarsal bone with
      pulmonary metastases. This is the first reported case of osteosarcoma at this
      site.

PMID- 10955879
TI  - Opinion divided on organ transplantation.

PMID- 10955880
TI  - Pheasant ataxia: a new condition in pheasant poults.
AB  - Between 1995 and 1997 a neurological condition in pheasant poults from 24 sites
      in England and Scotland was investigated. Affected birds showed varying degrees
      of ataxia and incoordinated movements and, in severe cases, recumbency, but
      generally remained alert with their heads held upright. The condition
      characteristically affected poults from seven weeks of age and the incidence on
      any one site was low. No significant bacteria were isolated consistently from
      brain tissue. The condition was characterised histologically by a non-suppurative
      meningoencephalitis, in which lesions were found predominantly in the cerebellum
      in 61 of 81 samples examined (75.3 per cent). A non-suppurative myelitis was
      recorded in 16 of 20 spinal cords examined. No lesions were recorded in
      peripheral neural tissue and lesions were rare in other tissues. The condition
      appeared not to have been recorded previously in pheasants. A viral aetiology was
      suspected but Newcastle disease virus was not involved.

PMID- 10955881
TI  - Conditions in grey seal pups (Halichoerus grypus) presented for rehabilitation.
AB  - A survey was carried out on the condition of 188 live grey seal (Halichoerus
      grypus) pups presented for rehabilitation from the coasts of south-west England
      between 1992 and 1998. The survey was carried out to assess the incidence of
      malnutrition, hyperthermia, respiratory and gastrointestinal conditions, and also
      the incidence of traumatic, skin, oral and ocular lesions. Malnutrition was a
      common finding in pups approaching weaning (mid-moult pups) and those at the
      point of weaning or postweaning (moulted pups) (62 per cent and 82 per cent,
      respectively). Separation from the dam, believed to be the main cause of
      malnutrition in grey seals, was encountered frequently in unweaned pups (91 per
      cent). Thirty-nine per cent of pups presented with a respiratory condition, 38
      per cent with hyperthermia and 9 per cent with diarrhoea. Seven per cent and 14
      per cent of pups had confirmed respiratory and gastrointestinal parasitic
      infestations respectively, although these were probably underestimates.
      Clinically significant traumatic lesions were seen in 41 per cent, oral
      ulceration in 26 per cent, ocular conditions in 13 per cent, nail bed infections
      in 13 per cent and oiling in 10 per cent of pups. Umbilical infections and other
      skin and oral conditions were also encountered. The incidence of these conditions
      is compared with data from dead grey seals, and clinical conditions in other
      pinniped species presented for rehabilitation.

PMID- 10955882
TI  - Observations of lameness, hoof conformation and development of lesions in dairy
      cattle over four lactations.
AB  - Lameness and lesions in the claws of 31 autumn-calving Holstein Friesian dairy
      cows were recorded from before their first-calving until their fifth lactation.
      The animals were managed by the same herdsman and housed adjacently in the same
      building in one of two herds grazed either on clover-rich pastures (herd 1) or on
      conventional ryegrass (herd 2). All four hooves were examined routinely four
      times during each lactation, and claw lesions were scored for severity and drawn
      on hoof maps. Heel erosion and infectious skin conditions of the hoof were also
      recorded, and hoof conformation, hardness, and growth and wear were measured. The
      animals' locomotion was scored weekly throughout the winter housing period and
      any observed to be lame were examined to determine the cause. The development of
      lesions was modelled by using hierarchic smoothing splines. There was no
      significant effect of herd except on the prevalence of lameness in lactation 2
      when the incidence of (inter)digital dermatitis was higher in herd 2. Lesion and
      locomotion scores were significantly higher by lactation 4 (P<0.05). There were
      significant effects (P<0.05) of weeks postcalving on lesion formation, claw
      conformation, and heel erosion.

PMID- 10955883
TI  - Possible distinction between sole ulcers and heel ulcers as a cause of bovine
      lameness.

PMID- 10955885
TI  - Coping with suicide.

PMID- 10955884
TI  - PMWS and porcine dermatitis nephropathy syndrome in Great Britain.

PMID- 10955886
TI  - Coping with suicide.

PMID- 10955887
TI  - Decisions on euthanasia.

PMID- 10955888
TI  - Mastitis and reduced cell counts.

PMID- 10955889
TI  - Reptiles and zoonoses.

PMID- 10955890
TI  - Fox predation as a cause of lamb mortality on hill farms.
AB  - Data collected between 1993 and 1996 from two Scottish hill farms were used to
      assess the potential importance of predation by foxes as a cause of lamb
      mortality. Farm 1 was in Midlothian and farm 2 in West Perthshire. Overall lamb
      mortality rates from birth onwards were 10.2 per cent for farm 1 and 9.3 per cent
      for farm 2. Sixteen lambs were identified as killed by foxes on the two farms
      during the four-year period. The minimum rates of fox predation were 0.6 per cent
      for farm 1 and 0.2 per cent for farm 2. All confirmed cases of fox predation were
      recorded during the period until the lambs were marked at about six weeks of age,
      and during this period another 53 lambs went missing from the two farms. Both
      groups of missing lambs were characterised by having significantly more siblings
      than the remaining lambs. A logistic regression model was able to classify the
      lambs killed by foxes and the missing lambs with 75 per cent accuracy on the
      basis of their birth rank alone. Of the total potential revenue from lamb
      production, the maximum losses due to confirmed fox predation in any one year
      were equivalent to 1.5 per cent on farm 1 and 0.6 per cent on farm 2.

PMID- 10955891
TI  - Closure of the abdominal wall at the umbilicus and the development of umbilical
      hernias in a group of foals from birth to 11 months of age.
AB  - The closure of the body wall defect at the umbilicus was studied in relation to
      the development of umbilical hernias in a group of 44 normal foals, 25 of which
      were followed from birth until five months of age, and 19 from birth until 11
      months of age. At birth, 19 of the foals had a defect in the body wall at the
      umbilicus that was termed a 'palpable umbilical ring'. In 18 of them this defect
      disappeared within four days, but in the other the ring did not close and a
      hernial sac with abdominal contents was palpable. This foal was considered to be
      the only foal to have a truly congenital umbilical hernia. Twelve foals developed
      an umbilical hernia between five and eight weeks of age. The prevalence of
      umbilical hernias was much higher than in other studies, possibly owing to the
      prospective nature of the study.

PMID- 10955892
TI  - Factors affecting the effectiveness of head-only electrical stunning in sheep.
AB  - The effects of factors such as the position of the tongs, the presence of wool,
      and the wetness of the skin on the efficiency of the head-only stunning
      procedure, and the duration of the periods of unconsciousness and analgesia were
      studied in lambs. The degree of insensibility was determined from the evaluation
      of physiological responses and electroencephalograms. The proportion of
      successfully stunned animals was significantly higher (P<0.05) in the animals
      stunned with the tongs in a frontal position than in those stunned with them in a
      caudal position, in the animals stunned with wet electrodes than in those stunned
      with dry electrodes and also in the animals without wool than in those with wool.
      The interval between stunning and sensibility to pain was affected significantly
      (P<0.01) only by the position of the tongs, being longer in animals with them in
      a frontal position than in those with them in a caudal position.

PMID- 10955893
TI  - Effect of condensed tannins extracted from four forages on the viability of the
      larvae of deer lungworms and gastrointestinal nematodes.
AB  - The inhibitory activity of condensed tannins extracted from four forage legume
      plants were evaluated by using a larval migration inhibition assay. The first
      (L1) and third (L3) stages of deer lungworm (Dictyocaulus viviparus), and the
      third stage (L3) of deer gastrointestinal nematodes were incubated with tannins
      extracted from Lotus pedunculatus, Lotus corniculatus, sulla (Hedysarum
      coronarium) and sainfoin (Onobrychus viciifolia). The tannins extracted from all
      the forages had inhibitory activity as measured by their ability to paralyse the
      larvae and inhibit them from passing through sieves. At the highest concentration
      used (1200 microg/ml) the tannins extracted from sainfoin had the highest
      activity against ensheathed L1 lungworm larvae (58 per cent), followed by L.
      pedunculatus (45 per cent), sulla (42 per cent) and L. comiculatus (35 per cent)
      when the larvae were incubated at 37 degrees C. The same trend, but with lower
      activities, was observed when the larvae were incubated at 22 degrees C.
      Anthelmintic activity against L3 lungworm larvae was evaluated by measuring the
      death rate of ensheathed L3 larvae after incubation with condensed tannins for
      two, 24 and 48 hours at room temperature (22 degrees C). The death rate was
      significantly higher (P<0.001) after 48 hours incubation than after two hours or
      24 hours, and significantly higher (P<0.001) after 24 hours than after two hours
      incubation. Condensed tannins from sainfoin had the highest inhibitory activity
      followed by L. pedunculatus, sulla and L. comiculatus. The tannins from sainfoin
      also had the highest activity against L3 larvae of gastrointestinal nematodes,
      followed by L. pedunculatus, sulla and L. comiculatus. Exsheathed larvae of
      gastrointestinal nematodes were significantly more susceptible to the action of
      the tannins than ensheathed larvae.

PMID- 10955894
TI  - Antimicrobial resistance patterns of Salmonella typhimurium and Salmonella dublin
      isolated from cattle in Japan.

PMID- 10955895
TI  - Microsporum canis associated with otitis externa in a Persian cat.

PMID- 10955896
TI  - Efficacy of an abamectin in-feed preparation against mites in pigs.

PMID- 10955897
TI  - Decisions on euthanasia.

PMID- 10955898
TI  - Hunting inquiry.

PMID- 10955899
TI  - Hunting inquiry.

PMID- 10955901
TI  - Coping with suicide.

PMID- 10955900
TI  - Hunting inquiry.

PMID- 10955902
TI  - Unusual case of bovine mucometra.

PMID- 10955903
TI  - Badgers and TB in cattle.

PMID- 10955904
TI  - Fungal transporters involved in efflux of natural toxic compounds and fungicides.
AB  - Survival of microorganisms in natural environments is favored by the capacity to
      produce compounds toxic to competing organisms and the ability to resist the
      effects of such toxic compounds. Both factors contribute to a competitive
      advantage of organisms in ecosystems. All organisms have evolved active transport
      mechanisms by which endogenous and exogenous toxicants can be secreted. Two major
      classes of transporter proteins are the ATP-binding cassette (ABC) and the major
      facilitator superfamily (MFS) transporters. Members of both classes can have
      broad and overlapping substrate specificities for natural toxic compounds and can
      be regarded as a "first-line defense barrier" in survival mechanisms. In plant
      pathogens, these transporters can play an essential role in protection against
      plant defense compounds during pathogenesis. Also, some transporters actively
      secrete host-specific and non-host-specific toxins. Remarkably, ABC and MFS
      transporters can also play a major role in fungicide sensitivity and resistance.
      Their role in multidrug resistance of Aspergillus nidulans, Candida albicans, and
      Saccharomyces cerevisiae to azoles and other fungitoxic compounds is well
      established. Knowledge of ABC and MFS transporters opens possibilities of
      developing novel strategies for controlling plant diseases, either by modulation
      of transporter activity or by transgenic expression of transporter genes in
      plants.

PMID- 10955905
TI  - A molecular phylogeny of Phytophthora and related oomycetes.
AB  - Phylogenetic relationships among 50 Phytophthora species and between Phytophthora
      and other oomycetes were examined on the basis of the ITS sequences of genomic
      rDNA. Phytophthora grouped with Pythium, Peronospora, and Halophytophthora,
      distant from genera in the Saprolegniales. Albugo was intermediate between these
      two groups. Unlike Pythium, Phytophthora was essentially monophyletic, all but
      three species forming a cluster of eight clades. Two clades contained only
      species with nonpapillate sporangia. The other six clades included either
      papillate and semipapillate, or semipapillate and nonpapillate types,
      transcending traditional morphological groupings, which are evidently not natural
      assemblages. Peronospora was related to P. megakarya and P. palmivora and appears
      to be derived from a Phytophthora that has both lost the ability to produce
      zoospores and become an obligate biotroph. Three other Phytophthoras located some
      distance from the main Phytophthora-Peronospora cluster probably represent one or
      more additional genera.

PMID- 10955906
TI  - A putative spectrin-containing membrane skeleton in hyphal tips of Neurospora
      crassa.
AB  - The apical plasma membrane (PM) is important in hyphal tip growth, where it may
      regulate tip extensibility via its association with an appropriate membrane
      skeleton (MS). By cell fractionation and immunocytochemistry we show that
      proteins with characteristics of actin, spectrin, and integrin are associated in
      a MS-like manner with the PM of Neurospora crassa hyphae. The spectrin-like
      protein in particular is highly concentrated at the PM in the region of maximum
      apical expansion. This protein shares with other spectrins immunoreactivity,
      molecular weight, PM association, and actin binding capacity. Its distribution in
      hyphae suggests that it is a dominant component of the MS in true fungi and is
      critical to hyphal tip growth.

PMID- 10955907
TI  - Plasma membrane-adjacent actin filaments, but not microtubules, are essential for
      both polarization and hyphal tip morphogenesis in Saprolegnia ferax and
      Neurospora crassa.
AB  - The organization and roles of F-actin and microtubules in the maintenance and
      initiation of hyphal tip growth have been analyzed in Saprolegnia ferax and
      Neurospora crassa. In hyphae of both species, the apex is depleted of
      microtubules relative to subapical regions and near-normal morphogenesis occurs
      in concentrations of nocodazole or MBC which remove microtubules, slow growth,
      and disrupt nuclear positioning. In contrast, each species contains
      characteristic tip-high arrays of plasma membrane-adjacent F-actin, whose
      organization is largely unaltered by the loss of microtubules but disruption of
      which by latrunculin B disrupts tip morphology. Hyphal initiation and subsequent
      normal morphogenesis from protoplasts of both species and spores of S. ferax are
      independent of microtubules, but at least in S. ferax obligatorily involve the
      formation of F-actin caps adjacent to the hyphal tip plasma membrane. These
      observations indicate an obligatory role for F-actin in hyphal polarization and
      tip morphogenesis and only an indirect role for microtubules.

PMID- 10955908
TI  - Cellular distribution of COT1 kinase in Neurospora crassa.
AB  - The Neurospora crassa cot-1 gene encodes a Ser/Thr protein kinase, which is
      involved in hyphal elongation. Many vacuoles, abnormally shaped mitochondria, and
      nuclei, along with differences in the structure of the cell wall and hyphal
      septa, were observed in hyphae of the cot-1 mutant shortly after a shift to the
      restrictive temperature. Immunolocalization experiments indicated that COT1 was
      associated with the cytoplasmic membrane; COT1 was also detected in the
      cytoplasm. The membrane-associated COT1 was absent from the cot-1 mutant when
      shifted to the restrictive temperature, as was a lower molecular weight isoform
      of COT1. We propose that COT1 may be involved in several cellular processes, and
      the spatial and temporal regulation of COT1 activity involves trafficking of the
      kinase within the fungal cell and its possible interaction with additional
      proteins.

PMID- 10955909
TI  - Phylogenetic analysis of Aspergillus section Circumdati based on sequences of the
      internal transcribed spacer regions and the 5.8 S rRNA gene.
AB  - Phenotypic features and sequences of the internal transcribed spacer (ITS)
      regions and the 5.8 S rRNA gene of type or neotype strains and other isolates of
      the 17 species currently assigned to Aspergillus section Circumdati and some
      potentially related species were analyzed. Parsimony analysis of sequence data
      indicated that Aspergillus section Circumdati is paraphyletic. Aspergillus
      campestris, A. lanosus, and A. dimorphicus with A. sepultus were found to be more
      closely related to Aspergillus sections Candidi, Flavi, and Cremei, respectively.
      These results were also supported by phenotypic data. A. robustus and A.
      ochraceoroseus were found not to be related to any of the species examined.
      Species of the proposed revised Aspergillus section Circumdati formed two main
      clades, which could also be distinguished based on phenotypic methods.
      Phylogenetic analysis of sequence data of other isolates assigned to species of
      the revised section indicates that either some of these isolates were
      misidentified or species concepts of A. ochraceus, A. melleus, and A. petrakii
      should be reconsidered.

PMID- 10955910
TI  - Interfacial self-assembly of fungal hydrophobins of the lichen-forming
      ascomycetes Xanthoria parietina and X. ectaneoides.
AB  - In the symbiotic phenotype of the lichen-forming ascomycetes Xanthoria parietina
      and X. ectaneoides, a conglutinate, hydrophilic cortex surrounds a system of
      aerial hyphae with hydrophobic wall surfaces. In X. parietina freeze-fracture
      electron microscopy showed that a rodlet layer covers the fungal and algal wall
      surfaces. Extracts of hot SDS-insoluble wall residues isolated from both species
      contained a protein that revealed a rodlet layer upon interfacial self-assembly.
      The N-terminal sequence of the 10-kDa protein of X. ectaneoides served to clone
      cDNA fragments of XEH1 (H1 of X. ectaneoides) and XPH1 (H1 of X. parietina) by RT
      PCR. Genomic DNA blot analysis with both lichenized species and the
      aposymbiotically cultured symbionts of X. parietina showed that XPH1 and XEH1 are
      fungal single copy genes. The deduced amino acid sequences of the two encoded
      proteins were 96% identical and showed the characteristics of class I
      hydrophobins.

PMID- 10955911
TI  - Obstructive airway disease caused by Moraxella catarrhalis after renal
      transplantation.
AB  - We report a case of severe acute obstructive airway disease 2 months after renal
      transplantation in a 16-year-old patient with Biedl-Bardet syndrome who was
      transplanted for end-stage renal failure secondary to cystic kidney disease.
      Symptoms of severe obstructive airway disease developed 2 months after
      transplantation under immunosuppression with prednisone, azathioprine, and
      tacrolimus. The patient did not develop signs of infection; progressive shortness
      of breath remained the only symptom for several weeks. After extensive diagnostic
      evaluation, bronchoalveolar lavage revealed Moraxella catarrhalis as the single
      infectious agent. After 3 weeks of appropriate antibiotic therapy, symptoms of
      obstructive airway disease were completely relieved. This atypical presentation
      of Moraxella infection in an immunocompromised host represents a rare
      complication of renal transplantation, especially in young patients. Special
      aspects such as frequency, diagnosis, differential diagnosis, and management of
      this rare complication of renal transplantation in a pediatric patient are
      discussed.

PMID- 10955912
TI  - Improved growth velocity with intensive dialysis. Consequence or coincidence?
AB  - Growth failure in children with end-stage renal disease remains a difficult
      problem. A 2.5-month-old baby in renal failure due to primary hyperoxaluria type
      I received intensive dialysis aimed at decreasing oxalate tissue accretion. Over
      5.5 months, while awaiting transplantation, his growth velocity was 29 cm/year
      compared with an average 4 cm/year in infants on hemodialysis and 22 cm/year in
      normal infants of this age. This remarkable growth rate, which could have
      represented catch-up growth, is hypothesized to be related to the delivered
      dialysis dose. It is suggested that this relationship be evaluated in a
      prospective randomized trial.

PMID- 10955913
TI  - Heparin-induced thrombocytopenia type II on hemodialysis: switch to danaparoid.
AB  - We report two pediatric patients with end-stage renal failure who developed
      heparin-induced thrombocytopenia type II (HIT II) on hemodialysis (HD). Both
      developed acute respiratory distress and chest pain within 30 min of initiating
      the 5th HD session. The platelets dropped during HD from 168 to 38x10(9)/l and
      from 248 to 109x10(9)/l, respectively. Marked clots were observed in the
      dialyzers. Substitution of heparin with the low molecular weight heparin
      dalteparin had no effect. Switching from anticoagulation to the heparinoid
      danaparoid resulted in immediate disappearance of all adverse effects, and
      further long-term HD was uneventful. HIT II was diagnosed clinically; heparin
      induced platelet activation test (HIPA) and serum IgG, IgA, and IgM to heparin
      platelet factor 4 complexes (HPF4) were both negative. We conclude that HIT II
      may occur in children on HD. HIT II is essentially a clinical diagnosis, as HIPA
      and antibodies to HPF4 are not always positive. Once HIT II is suspected, heparin
      (and low-molecular-weight heparins) should be stopped immediately. Long-term
      anticoagulation with danaparoid is a valuable option for patients on HD.

PMID- 10955914
TI  - Can the DOQI guidelines be met by peritoneal dialysis alone in pediatric
      patients? Dialysis Outcomes Quality Initiative.
AB  - DOQI guidelines recommend minimal standards for automated peritoneal dialysis
      (APD), with a weekly Kt/V of 2.1 and creatinine clearance (Ccr) of 63 l/1.73 m2.
      The purpose of this study was to assess if the DOQI guidelines could be met by
      dialysis alone in children on PD. Dialysis clearance studies were retrospectively
      analyzed in 20 pediatric patients on APD, all with a dwell volume of at least
      1,000 ml/m2. Mean dialytic Kt/V was 2.0; only 45% had a Kt/V above the
      recommended 2.1. Mean dialytic Ccr was 43.5 l/week per 1.73 m2; only 10% achieved
      a Ccr above the recommended 63 l/week per 1.73 m2. Despite the significant
      correlation between total therapy volume (TTV) and both Kt/V and Ccr, only 2 of
      10 patients with a TTV over 10 l/m2 per day reached the target Ccr. All patients
      had currently recommended dwell volumes, therapy times, and nocturnal cycles, but
      DOQI guidelines were difficult to achieve with dialysis alone. Strict adherence
      to DOQI guidelines in anephric pediatric PD patients may result in changing
      dialysis modality. However, without evidence of a correlation between delivered
      dose of dialysis and improved outcome, adequate dialysis should not be assessed
      by only measuring Kt/V and Ccr.

PMID- 10955915
TI  - Resistance to growth hormone and insulin-like growth factor-I in acidotic rats.
AB  - Growth impairment induced by chronic metabolic acidosis is associated with an
      abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To
      examine the potentially beneficial effects of IGF-I on acidosis-induced growth
      impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis,
      three groups of acidotic young rats (untreated, AC, n=12; treated with
      recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8)
      were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair
      fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of
      treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH
      receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH
      binding protein (GHBP), and IGF-I concentrations (mean+/-SEM) were analyzed.
      Significant decreases of 4.7-kb GH receptor [26+/-2 vs. 49+/-6 arbitrary
      densitometry units (ADU)] and 7.5 kb IGF-I (41+/-3 vs. 104+/-10 ADU) transcripts
      and low serum GHBP (25+/-1 vs. 32+/-1 ng/ml) and IGF-I (279+/-50 vs. 366+/-6
      nmol/l) levels were found in the AC compared with the C rats. The majority of
      these alterations were also observed in PF rats. Compared with acidotic untreated
      rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment
      normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition
      of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I.
      In contrast, IGF-I administration depressed the hepatic expression of all GH and
      IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm
      that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of
      associated malnutrition, and induced growth retardation that is resistant to GH
      therapy. Our study also shows that administration of IGF-I does not accelerate
      the growth of acidotic rats, suggesting a peripheral mechanism, at the level of
      target tissues, is responsible for the resistance to the growth-promoting actions
      of GH and IGF-I.

PMID- 10955916
TI  - Isoproterenol inhibits fibroblast growth factor-2-induced growth of renal
      epithelial cells.
AB  - The signal transduction pathways modulating bFGF effects in renal tubular
      epithelial cells (RTEc) are not completely understood. Since the cAMP and the
      mitogen-activated protein kinase (MAPK) pathways can modulate the growth of RTEc,
      we studied whether two cAMP elevating agents, isoproterenol and 8-bromo-cAMP,
      would modulate basic fibroblast growth factor (bFGF) induction of MAPK activity
      (ERK-2) and cell proliferation in human renal proximal tubular epithelial cells
      (RPTEc) and Madin-Darby canine kidney cells (MDCK clone EI1). Isoproterenol, but
      not bFGF, stimulated cAMP production in RPTEc and MDCKEI1 cells. bFGF,
      isoproterenol, and 8-bromo-cAMP alone increased ERK-2 activity in both cell
      types. However, isoproterenol and 8-bromo-cAMP partially inhibited the bFGF
      induction of ERK-2 activity, but only isoproterenol inhibited the proliferation
      of both cell types. PD098059 (25 microM), an inhibitor of MAPK kinase (MEK 1/2),
      blocked the bFGF mitogenic effects, but did not affect the 8-bromo-cAMP-induced
      mitogenic effects in MDCKEI1 cells. These findings suggest that activation of ERK
      2 is required but not sufficient for mitogenesis in RTEc. We conclude that
      isoproterenol inhibits the growth-promoting effects of bFGF in RTEc via MEK
      dependent and -independent pathways.

PMID- 10955917
TI  - Altered renal function in growth-restricted newborn piglets.
AB  - The effect of intrauterine growth restriction (IUGR) on renal hemodynamics and
      excretory functions was studied in 76 newborn piglets 12-27 h old. The
      experiments were performed on anesthetized animals divided into normal-weight
      piglets and IUGR piglets according to their birth weight. The "normal-weight"
      category included animals with a birth weight >40th percentile (piglets heavier
      than 1,220 g); the IUGR category included animals with a birth weight >5th and
      <10th percentiles (piglets with a birth weight between 733 g and 853 g). Cardiac
      output and renal blood flow were measured by the colored microsphere technique.
      Urine was collected from catheters placed in the ureters. This animal model of
      naturally occurring growth retardation in swine gives asymmetric growth with an
      increase in the mean ratio of brain weight to liver weight from 1.02 to 1.85
      (P<0.01). Thus there was only a small reduction in brain weight (11%). In
      contrast, the reduction in the weight of liver (50%) and kidney (46%) was
      proportional to that in body weight (46%). Heart rate, cardiac output, arterial
      blood gases, and pH were similar in normal-weight and IUGR piglets, but arterial
      blood pressure and arterial glucose content were significantly reduced in IUGR
      piglets (P<0.01). Moreover, IUGR piglets had higher plasma catecholamine levels
      (P<0.05). Renal blood flow and renal vascular resistance were similar in the
      normal-weight and in the IUGR groups. However, in IUGR animals, glomerular
      filtration rate was significantly less than in the controls (P<0.05). Normal
      weight and IUGR newborn piglets reabsorbed sodium very efficiently, the
      fractional sodium excretion was less than 1% in both groups. We conclude that
      renal blood flow is maintained in relation to kidney and body weight in IUGR
      newborns, but that important renal excretory functions are compromised due to
      IUGR.

PMID- 10955918
TI  - Alpha-tocopherol modulates lipoprotein cytotoxicity in obstructive nephropathy.
AB  - Oxidative stress in unilateral ureteral obstruction (UUO) contributes to the
      development of glomerular and tubulointerstitial lesions. The present study
      investigated whether oxidized low-density lipoprotein (oLDL) contributes to the
      pathogenesis of kidney injury in UUO, and whether alpha-tocopherol modulates such
      cytotoxicity and promotes repair. Male Sprague-Dawley rats weighing 100-125 g
      were assigned to three groups of 6 animals each: (1) sham, regular chow; (2) UUO,
      regular chow; and (3) UUO, alpha-tocopherol supplementation. We found a
      significant increase in the level of oxidative stress in the UUO group as
      measured by malondialdehyde (MDA) content in both plasma and kidneys. The LDL
      isolated from this group was cytotoxic to rat mesangial cells. The level of
      oxidation and cytotoxicity was significantly reduced when animals were treated
      with alpha-tocopherol. Plasma cholesterol concentration, kidney MDA, and
      transforming growth factor beta1 mRNA expression were all significantly increased
      in the UUO animals, and partially reduced in alpha-tocopherol-treated animals.
      Our data suggest that oxidative modification of LDL is associated with the renal
      injury in UUO. Taken together, our data support the concept that alpha-tocopherol
      can modulate LDL oxidation and its cytotoxic effects on rat mesangial cells in
      vitro.

PMID- 10955919
TI  - Membranous nephropathy with anti-tubular basement membrane antibody may be X
      linked.
AB  - The association of membranous nephropathy with Fanconi syndrome and anti-tubular
      basement antibodies appears to be a distinct subset of familial membranous
      nephropathy. We studied two Chinese families with four affected boys to evaluate
      the mode of inheritance of disease. HLA haplotype analysis of the family members
      in these two pedigrees did not reveal any significant linkages. However,
      microsatellite analysis of both pedigrees using markers on the X chromosome
      suggested linkage to the long arm of the X chromosome between the microsatellite
      markers DXS1001 and DXS1227. Identification and analysis of additional pedigrees
      may allow more precise mapping of the disease gene for anti-tubular basement
      membrane antibody-associated membranous nephropathy.

PMID- 10955920
TI  - Multicystic kidney dysplasia and Turner syndrome: two cases and a literature
      review.
AB  - Renal malformations occur in 33%-70% of cases of Turner syndrome (chromosome 45
      and variants). We describe two cases of multicystic dysplastic kidney in Turner
      syndrome. A literature review of renal abnormalities in Turner syndrome shows the
      frequency of cystic disease to be 1.76%. In multicystic dysplastic kidney,
      diagnostic investigation of the contralateral kidney, including voiding
      cystourethrography, is necessary in view of the high incidence of associated
      diseases (15%-20% of cases, vesicoureteric reflux) and other anomalies.

PMID- 10955921
TI  - Sporadic case of X-chromosomal Alport syndrome in a consanguineous family.
AB  - Alport syndrome (AS) is a genetic disorder of basement membranes caused by
      mutations in type IV collagen genes that is characterized by chronic hematuria
      and progressive nephropathy leading to renal failure. The main extrarenal
      features include sensorineural hearing loss and ocular lesions. The mode of
      inheritance is X-linked dominant in about 80%-85% of the affected families,
      whereas autosomal transmission is rarely encountered. We report a male patient
      originating from a healthy consanguineous Lebanese family who presented with an
      unusual association of obstructive uropathy and AS. Hematuria and proteinuria
      were initially attributed to a suspected poststreptococcal glomerulonephritis
      (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after
      medical treatment of poststreptococcal GN and surgical correction of obstructive
      uropathy finally led to renal biopsy. The observed ultrastructural changes of the
      glomerular basement membrane were typical for AS. Molecular genetic studies
      revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding
      maternal heterozygotic carrier status. This case report emphasizes the importance
      of hereditary nephritis in the differential diagnosis of chronic hematuria, and
      demonstrates the value of molecular studies for genetic counselling in AS.

PMID- 10955922
TI  - Autosomal recessive inheritance of von Willebrand factor-cleaving protease
      deficiency.
AB  - A child with chronic relapsing thrombotic thrombocytopenic purpura (TTP/HUS) had
      recurrent thrombocytopenia, microangiopathic hemolytic anemia with fragmented
      erythrocytes, microthrombi in the lung vessels, and renal dysfunction. Assay of
      von Willebrand factor (vWF)-cleaving protease showed a complete protease
      deficiency in the patient and subnormal activities in the mother and in two
      asymptomatic siblings. No inhibitor of vWF-cleaving protease was detected in the
      patient's plasma. Periodic transfusions of fresh-frozen plasma prevented further
      acute episodes of TTP/HUS. Specific diagnosis of the constitutional deficiency of
      vWF-cleaving protease helps to provide successful prophylactic therapy.

PMID- 10955923
TI  - Variability among pediatric nephrologists in the initial therapy of nephrotic
      syndrome.
AB  - The objective of this study was to describe the practices of North American
      pediatric nephrologists in treating new-onset steroid-sensitive nephrotic
      syndrome and impressions regarding the effect of therapy duration on the risk of
      relapse. A questionnaire was mailed to 130 pediatric nephrologists in the United
      States and Canada. One hundred and five (81%) replied. Of the respondents, 39%
      believed a longer steroid regimen results in more-sustained remissions; 19% did
      not; 18% believed perhaps, but not enough to risk the increased side-effects of
      the longer steroid regimen; and 24% did not know. Half of the respondents
      prescribed an 8-week regimen and 21% prescribed a 12-week regimen; however, in
      70% of both regimens, respondents appended an additional taper. The remaining
      respondents either tapered at urinary remission (14%) or used another regimen
      (15%). Physicians using the 12-week regimen expected 44% of patients to be
      relapse free at 1 year, compared with 31% of patients of respondents using other
      regimens (P=0.005). Over the previous 5 years, 38% of respondents changed their
      approach; of these, 70% lengthened the treatment course. Physician perceptions
      and strategies did not vary according to years of clinical experience. In
      conclusion, there is significant variability in practice and perceptions among
      pediatric nephrologists; however, most have extended therapy beyond the
      traditional 8-week course.

PMID- 10955924
TI  - Management of steroid-responsive nephrotic syndrome.

PMID- 10955925
TI  - Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome.
AB  - Development of steroid dependency represents a significant therapeutic challenge
      in steroid-sensitive nephrotic syndrome. Previous studies have shown conflicting
      results concerning the benefit of a 12-week treatment with cyclophosphamide
      (CPO), with 24%-67% of patients achieving long-term remission. We therefore
      analyzed the clinical response of 20 consecutive children with steroid-dependent
      nephrotic syndrome (SDNS) (12 male, median age at start of treatment 5.9 years,
      range 3.2-14.7 years) treated at our institution with CPO (2 mg/kg per day) for
      12 weeks since 1989. Median duration of follow-up was 5.8 (range 1.1-9.25) years.
      Only 6 of 20 children (30%) showed a long-term remission of >2 years, while 14 of
      20 (70%) developed relapses again. Of these, 12 patients (86%) again developed
      steroid dependency, requiring further alternative treatment. Our data show that a
      12-week course of CPO leads to unfavorable results in the majority of patients
      with SDNS. We therefore conclude that there is a need for further optimization of
      therapy in SDNS.

PMID- 10955926
TI  - Efficacy of long-term azathioprine for relapsing nephrotic syndrome.
AB  - Seven patients who had an initial attack of nephrotic syndrome in childhood and
      had frequent relapses even after cyclophosphamide therapy were given a 2-year
      course of azathioprine. The mean annual relapse rates decreased from 2.4+/-0.5 in
      the year preceding azathioprine to 0.4+/-0.8 in the 1st and 2nd years after its
      initiation. All six patients who were observed for more than 6 months after
      discontinuation of the therapy were relapse free for this period. Average doses
      of prednisolone could also be decreased in the 2nd and subsequent years after the
      therapy. There were no significant toxic effects. Long-term azathioprine therapy
      may be well tolerated and effective for nephrotic patients with frequent
      relapses.

PMID- 10955927
TI  - Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome.
AB  - T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of
      the study was to determine whether the activity of T-helper-1 (Th1) and T-helper
      2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+
      ("naive" helper T cells, suppressor-inducer), CD45RA+CD8+ ("naive" suppressor T
      cells, suppressor-effector), CD45RO+CD4+ ("memory" helper T cells), are
      predictive for steroid sensitivity in children with primary NS. These parameters
      were assessed at the onset of disease, before initiation of steroid therapy. Two
      groups of NS children were retrospectively formed according to steroid
      sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was
      defined by the production of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL
      10 in the supernatants of CD4+ T cell cultures activated with autologous
      monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were
      determined using double- or triple-color flow cytometry. In SS children with NS
      we found a decreased proliferative response of CD4+ T cells to TT stimulation,
      cytokine synthesis indicating the predominance of Th2 activity, and an increased
      percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18+/-0.8,
      P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05+/-0.6, P<0.01) cells,
      with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2+/
      0.1, P<0.001). In children with SRNS we found an increased proliferative response
      of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82+/-0.7,
      P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85+/-0.6,
      P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+
      CD25+, 0.5+/-0.2, P<0.05) T cells. We conclude that prior to treatment the
      distribution of lymphocyte subpopulations in peripheral blood together with Th1
      and Th2 cell activity provides a useful tool for evaluating the likelihood of
      steroid sensitivity in patients with primary NS.

PMID- 10955928
TI  - Acute non-proliferative glomerulitis: a cause of renal failure unique to
      children.
AB  - Over a 31-year period, we have encountered 13 children with a disease entity not
      reported by other clinics that leads to rapidly progressive crescentic
      glomerulonephritis. Gross hematuria, rapidly declining renal function, and a
      serum C3 level at the lower limit of normal or slightly depressed usually
      characterized the disease onset; hypertension and nephrotic syndrome were absent.
      Glomerular IgG was absent, but large C3-containing subepithelial deposits on the
      paramesangial basement membrane (GBM) were always present. Because of these
      deposits and because dense alteration of the GBM was found in 3 patients, the
      disease may resemble membranoproliferative glomerulonephritis type II, but is
      distinguishable on other morphological and clinical grounds. The absence of anti
      neutrophil cytoplasmic antibody, tested for in 5 of 13 patients, is one of
      several ways the disease differs from the pauci-immune glomerulonephritis of
      adults. Clinically and by glomerular morphology, it also differs from severe
      poststreptococcal acute glomerulonephritis. Treatment with high-dose
      corticosteroids has been highly successful. Because in this series the disease
      occurred only in children under age 12 years and the amount of silver-positive
      mesangial matrix was normal, indicating absence of mesangial proliferation, it
      has been designated juvenile acute non-proliferative glomerulitis.

PMID- 10955929
TI  - Decreasing hypocomplementemia and membranoproliferative glomerulonephritis in
      Japan.
AB  - The number of patients with membranoproliferative glomerulonephritis(MPGN)
      diagnosed in our institution and the incidence of hypocomplementemia as
      determined by school urinary screening programs in Japan were investigated
      retrospectively. Fifty-seven children were diagnosed as having MPGN between 1974
      and 1997. Of these, 13 patients were diagnosed during period 1 (1974-1979) and 25
      during period 2 (1980-1985). A decreasing trend was observed during periods 3
      (1986-1991) (12 patients) and 4 (1992-1997) (7 patients) compared with period 2
      (P<0.05 and P<0.01, respectively). A significant difference was also noted when
      MPGN was compared between periods 1 and 2 (1974-1985) and periods 3 and 4 (1986
      1997) (P<0.01). Serum C3 was measured in 1,282 school children with abnormal
      urinary findings between 1980 and 1997. Thirty children had hypocomplementemia.
      The incidence of hypocomplementemia was significantly lower in period 3 (1986
      1991) (9 children) and period 4 (1992-1997) (2 children) compared with period 2
      (1980-1985) (19 children) (P<0.05 and P<0.01, respectively). New cases of MPGN in
      our institution and the incidence of hypocomplementemia as determined by school
      urinary screening programs are decreasing in Japan. The reason for this trend is
      unknown.

PMID- 10955930
TI  - Vascular C3 deposits on renal biopsy in pediatric patients with hematuria.
AB  - Isolated deposition of the third component of complement (C3) in the renal
      arterioles has been noted on biopsy specimens in patients with hematuria. This
      entity is of little known significance and reports of this finding in pediatric
      patients with hematuria are rare. We reviewed the clinical histories and biopsies
      of 17 children with hematuria and vascular C3 deposition on biopsy at Texas
      Children's Hospital over an 14-year period. The mean age of presentation was 10.8
      (range 4.5-16.6) years with a male preponderance (71%). Family history for
      hematuria was positive in 6 of 17 patients (35%). Light microscopy was normal or
      showed only minor abnormalities. Immunofluorescence was negative for IgA and IgG
      in all patients. Seven patients (41.1%) were noted to have diffuse or focally
      thin basement membranes on electron microscopy in addition to positive C3
      immunofluorescence. The mean follow-up time was 23.8 months, during which 2 of 17
      patients (12%) developed worsening proteinuria. The etiopathogenesis of this
      condition remains unclear, but an underlying immunological process cannot be
      ruled out. It is possible that this condition represents a stage of an acute
      glomerulonephritis. Clinical follow-up of these patients is warranted, as the
      long-term prognosis remains unclear.

PMID- 10955931
TI  - Ambulatory blood pressure monitoring in children: a large center's experience.
AB  - Ambulatory blood pressure monitoring (ABPM) is well established in adults and is
      becoming common in children. We reviewed 190 ABPM studies retrospectively (since
      1990) to assess the failure rate, and analyzed the data from 97 patients 5-19
      years old (1992-1996) to review the experience gained from the use of this
      technique in children and adolescents. Seventeen percent (32/190) of studies
      failed. Most children accepted ABPM, provided it was clearly explained in
      advance. There were differences between day and night readings of systolic blood
      pressure (BP), diastolic BP, and heart rate. BP did not correlate with height or
      weight. "White coat" effect apparently exists in children: clinic systolic BPs
      were higher than daytime systolic ABPM (no difference in diastolic). Eighty-nine
      percent (86/97) had an elevated BP load (>30% of readings >95th percentile). The
      antihypertensive medications of 16% (16/97) of patients were changed after ABPM.
      The nocturnal fall in BP (expressed as a percentage of the individual mean
      daytime values) was approximately normally distributed and was independent of age
      and height. Nocturnal systolic and diastolic dipping were closely correlated.
      Attenuation of nighttime dipping was observed in children with kidney disease and
      those with organ transplants. There is a need for normative data for ABPM for
      North American children. In our study, the technique was useful in selected
      cases, such as borderline or secondary hypertension, and for therapeutic
      monitoring when BP control is difficult.

PMID- 10955932
TI  - Renovascular disease and hypertension in children with neurofibromatosis.
AB  - Neurofibromatosis type 1 (NF1) is associated with vascular lesions, such as renal
      artery stenosis, and secondary hypertension. The real prevalence is largely
      unknown, particularly in children. We observed 27 patients with NF1, mean age
      12.8 years (range 4.2-24 years), for 2-10 years to assess the association of NF1
      with vascular abnormalities and secondary hypertension. Patients were studied
      with angiography, 24-h blood pressure monitoring, a captopril test, and Doppler
      ultrasonography of aorta and renal arteries. The prevalence of hypertension was
      18.5%; 61.5% of patients studied with angiography had vascular lesions, half of
      whom were apparently normotensive. However, they had abnormal 24-h blood pressure
      monitoring, which was a first sign of poor blood pressure control. Those patients
      with severe hypertension (11.1%) were successfully treated with percutaneous
      transluminal angioplasty (PTA); stenosis recurred in 2 of 3 patients after a 2
      year follow-up period, and was responsive to drugs. We conclude that hypertension
      is a frequent complication of NF1 in pediatric patients, it is usually secondary
      to typical vascular lesions, and requires careful follow-up. Ambulatory blood
      pressure monitoring (24-h) is a sensitive method for detecting initial
      alterations of the blood pressure pattern. PTA may be an effective treatment in
      this condition.

PMID- 10955933
TI  - Child abuse in an infant presenting as unexplained acute systemic hypertension.
AB  - Hypertension in the infant is uncommon and is usually associated with renal
      vascular or parenchymal disease, coarctation or thrombosis of the aorta, or
      chronic lung disease. A 3-month-old infant who presented with unexplained acute
      systemic hypertension was subsequently discovered to have an undiagnosed femoral
      fracture secondary to child abuse. Undiagnosed fractures, which are often
      associated with child abuse, should be considered in the differential diagnosis
      of an infant presenting with unexplained systemic hypertension.

PMID- 10955934
TI  - Plasma brain natriuretic peptides and renal hypertension.
AB  - Three children with renal hypertension are described. Two had histories of
      neuroblastoma treated by surgical resection and chemotherapy. They both presented
      later with unilateral atrophic kidney and marked hypertension. Only the child
      with severe cardiac failure demonstrated high plasma brain natriuretic peptide
      (BNP) concentrations. The remaining patient had a history of chronic nephritis
      treated with continuous ambulatory peritoneal dialysis. She also had chronic
      hypertension and severe cardiac failure. This child demonstrated high plasma BNP
      levels. The endogenous secretion of BNP is not triggered by hypertension alone,
      even though exogenous BNP has the pharmacological effect of reducing renin
      activity.

PMID- 10955935
TI  - Yield of renal arteriography in the evaluation of pediatric hypertension.
AB  - The prevalence of renovascular disease is estimated to be 3%-5% in pediatric
      patients with hypertension. The utility of non-invasive imaging tests has not
      been evaluated in children, and renal arteriography remains the diagnostic test
      of choice. However, there are no established guidelines for the application of
      this test and information is not available about the likelihood of detecting an
      abnormality if an arteriogram is performed in children with hypertension.
      Therefore, we reviewed the yield of renal arteriography in pediatric patients if
      the test was performed based on the following two criteria: (1) severe
      hypertension exceeding the 99th percentile for age and sex or (2) failure to
      control high blood pressure with one antihypertensive drug. During the period
      1983-1998, 28 children (mean age 11.7 years) who satisfied one of the above
      criteria underwent renal arteriography to investigate hypertension. None of the
      patients were renal transplant recipients. The average duration of hypertension
      was 11 months and the peak blood pressure was 168/107 mmHg. The renal arteriogram
      was abnormal in 12 patients (43%). Unilateral renal artery stenosis was the most
      common abnormality. When the patients were divided into two groups - those with
      an abnormal or normal test result - they did not differ in age, sex, or racial
      distribution. The peak systolic blood pressure was higher in children with an
      abnormal renal arteriogram (P<0.05). Among those undergoing the arteriogram on
      the basis of the first criterion, i.e., severe hypertension, 11 of 23 (48%)
      studies were abnormal. Five children had an arteriogram based on the second
      criterion--failure to control the blood pressure with one medication--and in 1
      patient (20%) the test was abnormal. We conclude that the prevalence of
      renovascular disease in a population of hypertensive children subjected to renal
      arteriography is around 40%. Two clinical criteria--namely severe hypertension or
      failure to control hypertension effectively with one drug--are useful to guide
      the application of renal arteriography in children with hypertension.

PMID- 10955936
TI  - Ureteropelvic junction obstruction: morphological and clinical studies.
AB  - This study included 27 patients with ureteropelvic (UPJ) obstruction. Both renal
      parenchyma and the junctional abnormality were examined and correlated with
      clinical findings. Renal biopsies were categorized into grades 1-4. Those with
      normal or minimal findings (grade 1 and 2, respectively) had excellent renal
      function as assessed by radionuclide studies. Those with grade 4 had severe
      histological abnormalities associated with poor renal function. Grade 3 renal
      changes were seen in patients whose renal function varied greatly and did not
      correlate with the extent of the limited histological abnormalities. Although
      there was great variation in the renal biopsies, glomerulosclerosis was a
      consistent finding, associated with extracapillary proliferation and periodic
      acid-Schiff-positive material (? Tamm-Horsfall protein) in the urinary space of
      glomeruli in 91% (10/11) of grade 3 or 4 renal biopsies. No extracapillary
      proliferation was seen in grade 1 renal biopsies. The UPJ obstruction area was
      consistently inflamed and markedly thickened due to varying degrees of
      perifascicular fibrosis and muscular hypertrophy. Extensive fibrosis with
      associated muscular atrophy was the most-severe change in this spectrum.

PMID- 10955937
TI  - Enhanced detection of vesicoureteric reflux with isotopic cystography.
AB  - We compared the accuracy of isotope cystography (IC) and fluoroscopic
      cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC
      and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2
      years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month
      period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The
      two methods were concordant for the detection of VUR in 84% of kidney-ureter
      units and in 93% for the detection or exclusion of severe VUR. IC detected VUR
      more accurately than FC, both when all grades of VUR were considered together
      (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed
      by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one
      side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more
      accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the
      method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC
      also need FC to investigate for posterior urethral valves.

PMID- 10955938
TI  - A giant urinoma in a neonate without obstructive uropathy.
AB  - We report a neonate with a giant urinoma and renal failure. A 7-day-old boy had a
      giant abdominal mass of 6.5 cm x 8 cm in the right quadrant, gastroesophageal
      reflux, and renal failure caused by the compression from the mass. Radiological
      observations revealed a multiseptated cyst and neither kidney could be detected.
      To relieve these symptoms percutaneous drainage was performed. The contents of
      the fluid were similar to the patient's urine. The symptoms were improved by the
      drainage, and we found the left kidney to be absent and the right kidney small.
      Four prenatal ultrasound scans detected no cystic lesions in his abdomen.
      Neonatal urinomas are commonly complicated by obstructive uropathy, such as
      posterior urethral valves or ureteropelvic junction obstruction. These
      obstructive uropathies were ruled out by retrograde pyelography and voiding
      cystourethrography. A severely dilated upper pole of a double collecting system
      was also ruled out by intravenous pyelography and direct observation of the
      kidney during an open biopsy. The cause of the urinoma is still uncertain, but
      trauma during delivery and the dysplastic right kidney may be involved.

PMID- 10955939
TI  - Gastrostomy buttons for nutritional support in children with cystinosis.
AB  - Poor growth in children with cystinosis may be a combination of sub-optimal
      nutritional intake, gastrointestinal dysfunction and polypharmacy. We report our
      experience with gastrostomy buttons (GBs) in five children (4 male) with
      cystinosis treated at a median age of 3 years (range 1.4-8.8 years). All children
      received overnight GB feeding for a mean duration of 27 months (range 7-42
      months). During 135 patient-months of observation, the mean life of the GB was
      5.7 months (range 3-7.7 months), with a mean of 3.4 GB changes (range 1-6) per
      patient. An average of five (range 3-7) medications were administered daily via
      the button. The mean energy intake achieved was 118% of the estimated average
      requirement (range 86%-183%), with 58% of total energy and 55% of protein intake
      being delivered via the GB during the study period. Mean height standard
      deviation score (SDS) was -3.79 at the start of GB feeding and -3.08 at the end
      of the study period, with mean weight SDS of -3.79 and -2.17 (P=0.042),
      respectively. The buttons have been welcomed by the families and should be
      considered as a treatment option for providing the nutritional prescription and
      administering medications.

PMID- 10955940
TI  - Gastroduodenal lesions and Helicobacter pylori in children with end-stage renal
      disease.
AB  - Thirty-seven children with end-stage renal disease were evaluated for
      gastroduodenal lesions by upper gastrointestinal endoscopy between January 1993
      and January 1998. The mean (+/-SD) age of the patients was 14.3+/-2.4 years
      (range 9-17 years). Endoscopic examination was abnormal in 17 patients (46%). The
      lesions were antral gastritis plus bulbitis (n=6), nodular bulbitis (n=4), antral
      gastritis (n=4), and duodenal ulcer (n=3). Fifteen patients had symptoms related
      to gastroduodenal disease, whereas 22 patients were asymptomatic at the time of
      endoscopic examination; 80% of the symptomatic and 23% of the asymptomatic
      patients had gastroduodenal lesions on endoscopy. Antral mucosal biopsy was taken
      from 26 of 37 children for the detection of Helicobacter pylori by the urease
      test. H. pylori was detected in 10 of 16 patients with gastroduodenal lesions (8
      symptomatic, 2 asymptomatic). None of the patients with normal endoscopic
      examination were positive for H. pylori. Thus, we have demonstrated a significant
      number of gastroduodenal lesions and their frequent association with H. pylori in
      our pediatric renal transplant candidates. Our results emphasize the importance
      of gastrointestinal evaluation in these patients. Endoscopic examination should
      be considered in symptomatic patients and in areas where H. pylori is endemic.

PMID- 10955941
TI  - Advanced glycation end products in adolescents and young adults with diabetic
      angiopathy.
AB  - The aim of this study was to evaluate serum advanced glycation end products (S
      AGEs) in a group of adolescents and young adults with type 1 (insulin-dependent)
      diabetes mellitus and with diabetic microvascular complications (nephropathy or
      retinopathy). Fifty-two patients were included in the study (age range 14.2-28.8
      years, onset of diabetes before the age of 12 years, duration of diabetes longer
      than 7 years); 45 patients without diabetic angiopathy and 63 healthy controls
      were also selected. S-AGEs were significantly increased in patients with diabetic
      angiopathy compared with controls (19.9+/-3.8 vs. 11.8+/-2.8 U/ml, P<0.001).
      Higher S-AGE levels were found in patients with severe diabetic nephropathy and
      retinopathy. When the albumin excretion rate (AER) was >100 microg/min per 1.73
      m2, S-AGE levels were 23.1+/-2.4 U/ml; when the AER was 50-100 microg/min per
      1.73 m2 levels were 19.8+/-1.9 U/ml, and for an AER of 20-50 microg/min per 1.73
      m2 the corresponding value was 16.1+/-2.1 U/ml (P<0.005). Patients with
      proliferative retinopathy had S-AGE levels of 22.2+/-2.6 U/ml, those with
      preproliferative retinopathy 20.7+/-2.2 U/ml, and background retinopathy 17.6+/
      1.9 U/ml (P<0.01). A significant correlation was found between levels of
      glycosylated hemoglobin (HbA1c) and S-AGE (r=0.43, P<0.01). S-AGE concentrations
      are markedly increased in type 1 diabetic adolescents and young adults with
      diabetic nephropathy and retinopathy. The severity of diabetic angiopathy is
      related to the serum levels of AGEs.

PMID- 10955942
TI  - Urinary calcium excretion in healthy Thai children.
AB  - The objective of this study was to determine age-specific reference values for
      urinary calcium/creatinine ratios (UCa/Cr) of children in southern Thailand. Non
      fasting urine samples were collected from a random population of 488 healthy
      children (282 males, 206 females) ranging in age from 17 days to 15 years.
      Samples were divided into six groups by age. Subjects whose calcium levels
      exceeded the 95th percentile within each age group were classified as having
      hypercalciuria. Pyuria, hematuria, proteinuria, urinary sodium, and potassium
      levels in children with normal UCa/Cr were compared with levels in children with
      high UCa/Cr. The 95th percentiles for UCa/Cr (mg/mg) by age were: <6 months,
      0.75; 6 months to <12 months, 0.64; 12 months to <2 years, 0.40; 2 years to <5
      years, 0.38; 5 years to <10 years, 0.29; and 10 years to <15 years, 0.26. Pyuria,
      hematuria, and proteinuria were no more prevalent in the 22 children with
      hypercalciuria than in children with normal urinary calcium levels. Urinary
      sodium/creatinine ratios (UNa/Cr) and urinary sodium/potassium ratios (UNa/K)
      were correlated with UCa/Cr (r=0.41, P<0.0001 and r=0.24, P<0.0001,
      respectively). Urinary potassium/creatinine ratios (UK/Cr) were not (r=0.05,
      P>0.1)). Children with high UCa/Cr ratios also had higher UNa/Cr and UNa/K (5.6+/
      7.1 vs. 2.6+/-1.5, P<0.001 and 5.4+/-2.3 vs. 2.5+/-0.23, P<0.05, respectively).
      The study established reference values for random, non-fasting UCa/Cr for healthy
      Thai children and indicated that urinalysis is not a good indicator of
      hypercalciuria.

PMID- 10955943
TI  - Exercise-induced acute renal failure in a patient with renal hypouricemia.
AB  - We describe a case of exercise-induced acute renal failure (ARF) in a patient
      with hypouricemia. Following recovery from ARF, the patient's serum urate
      concentration was 0.6-0.9 mg/dl, and the ratio of urate clearance to creatinine
      clearance (Cua/Ccr) was 41.9%-56.6%. There was no change in the Cua/Ccr following
      the administration of pyrazinamide or probenecid, suggesting defects of tubular
      urate/anion exchangers. Because the renal biopsy revealed acute tubular necrosis
      without uric acid crystals, the ARF of this patient might be due to oxygen free
      radicals resulting from exercise stress and hypouricemia.

PMID- 10955944
TI  - Atrial natriuretic peptide in children with idiopathic hypercalciuria.
AB  - We measured plasma atrial natriuretic peptide (ANP) levels in 30 children with
      idiopathic hypercalciuria (IH) and 19 normal controls (NC). A calcium (Ca)
      loading test was performed in all patients to determine the type of IH.
      Subsequently plasma ANP, cAMP and renin activity (PRA), serum total and ionized
      Ca, intact parathyroid hormone, aldosterone, and 1,25-dihydroxyvitamin D as well
      as urine Ca, cAMP, and electrolytes were determined in all subjects. The mean
      (SD) plasma ANP levels were significantly lower in patients with renal
      hypercalciuria (RH) [21.4 (4.8) pg/ml] than in those with absorptive
      hypercalciuria (AH) [26.8 (7.6) pg/ml, P<0.05] and NC [27.6 (6.6) pg/ml,
      P<0.001]. PRA was significantly lower in AH [2.9 (1.3) ng/ml per hour] than in RH
      patients [7.8 (6.8) ng/ml per hour, P<0.01] and in NC [6.8 (4.6) ng/ml per hour,
      P<0.005]. Serum aldosterone values were significantly lower in AH [14.5 (11.4)
      ng/dl] than in RH patients [25.4 (14.1) ng/dl, P<0.05] and in NC [32.6 (20.5),
      P<0.001]. The lower plasma ANP levels in RH than in AH patients and in NC may be
      due to Ca depletion. The lower PRA and serum aldosterone levels in AH than in RH
      patients and in NC may be attributed to Ca excess.

PMID- 10955945
TI  - Chronic renal failure and portal hypertension--is portosystemic shunt indicated?
AB  - We report two girls with histories of recessive polycystic kidney disease. Both
      were on maintenance hemodialysis. They had undergone surgical distal portocaval
      shunt because of portal hypertension. Later, bilateral nephrectomy was performed,
      and they presented with hepatic encephalopathy (HE) and evolution towards
      irreversible hepatic coma and death. Portosystemic shunt is the treatment of
      choice of portal hypertension. The kidney plays a pivotal role in ammonia
      disposal during portosystemic shunt. Thus, we stress the risk of HE after
      portosystemic shunt followed by bilateral nephrectomy in patients with end-stage
      renal failure and suggest that combined liver-kidney transplantation should be
      considered.

PMID- 10955946
TI  - Interstitial cystitis and ileus in pediatric-onset systemic lupus erythematosus.
AB  - A girl aged 11 years presented with autoimmune hemolytic anemia with
      thrombocytopenia, and subsequently developed severe abdominal pain, vomiting, and
      pollakiuria. X-ray findings of her abdomen demonstrated paralytic ileus with
      intestinal wall thickening. Intravenous pyelography revealed bilateral
      hydroureter with mild hydronephrosis and contracted bladder. Pathological
      examination of her bladder revealed interstitial cystitis, with evidence of focal
      deposition of IgG and C3 in a granular pattern on small blood vessel walls. She
      was diagnosed as having systemic lupus erythematosus (SLE) associated with
      paralytic ileus and chronic interstitial cystitis. Although initiation of high
      dose prednisolone therapy resulted in a gradual improvement in clinical symptoms,
      reducing the dosage of prednisolone caused a relapse. To our knowledge, the
      combination of paralytic ileus and chronic interstitial cystitis is quite
      uncommon in pediatric-onset SLE.

PMID- 10955947
TI  - Wegener granulomatosis--an atypical case.
AB  - An unusual sequence of the clinical manifestations of microvascular disease is
      described in a 15 year-old girl. She initially presented with acute renal failure
      caused by a crescentic glomerulonephritis associated with positive tests for MPO
      ANCA. Eighteen months later she had pulmonary hemorrhage and respiratory failure.
      An open lung biopsy showed granulomas that were diagnostic for Wegener
      granulomatosis. We discuss the diagnostic dilemmas faced in attempts to
      distinguish infective causes of pulmonary granulomas, such as tuberculosis or
      fungi, from granulomas associated with vasculitis, in a patient previously
      treated with immunosuppressive therapy.

PMID- 10955948
TI  - Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic
      syndrome.
AB  - The pathogenesis of proteinuria in idiopathic minimal lesion nephrotic syndrome
      (IMLNS) remains to be elucidated. The most-accepted hypothesis is that the
      increased glomerular permeability to plasma proteins results from the effect of
      circulating factors on glomerular capillaries. This report critically reviews the
      current studies that have attempted to isolate and characterize this putative
      factor(s). Products released from hepatocyte or peripheral blood mononuclear
      cells or isolated by chromatography from serum or plasma have been tested in rats
      for their role in inducing proteinuria. These factors have been infused into the
      isolated kidney preparation or into the intact animal as a single venous
      injection, or continuously by pump for a period of 4 h to 7 days. Several of
      these isolated factors have been shown to induce proteinuria in rats. However,
      their exclusive pathogenetic role is questionable since none is always present in
      all IMLNS patients during relapse. Therefore, the increase in proteinuria in
      these patients may result from a single or a variety of factors as yet to be
      identified.

PMID- 10955949
TI  - Clinical quiz. Ectopic ureter.

PMID- 10955950
TI  - Endothelin-1 and von Willebrand factor in pseudoxanthoma elasticum.

PMID- 10955951
TI  - Pseudohypoaldosteronism type 1 and respiratory distress syndrome.

PMID- 10955952
TI  - Coinfection of fibroblasts with Coxiella burnetti and Toxoplasma gondii: to each
      their own.
AB  - Intracellular pathogens have evolved distinct strategies to subvert host cell
      defenses. At diametrically opposed ends of the spectrum with regard to the host
      endosomal/lysosomal defenses are the obligate intracellular protozoan Toxoplasma
      gondii and the bacterium Coxiella burnetti. While the intracellular replication
      of T. gondii requires complete avoidance of the host endocytic cascade, C.
      burnetti actively subverts it. This results in these organisms establishing and
      growing in very different vacuolar compartments. In this study we examined the
      potential interaction between these distinct compartments following coinfection
      of mammalian fibroblasts. When present within the same cell, these organisms
      exhibit minimal interaction with each other. Colocalization of T. gondii and C.
      burnetti within the same vacuole occurs at a low frequency in doubly infected
      cells. In such instances only one of the organisms appears to be replication
      competent, emphasizing the different requirements for survival and/or
      intracellular growth. The potential basis for both the lack of interaction
      between these distinct pathogen-containing compartments, and the mechanisms to
      address their low frequency of colocalization are discussed in the context of our
      understanding of the biology of the organisms and membrane traffic in eukaryotic
      cells.

PMID- 10955953
TI  - PCR-based quantification of Pneumocystis carinii in in vitro systems.
AB  - In many laboratories, PCR has become a routine method for the sensitive diagnosis
      of Pneumocystis carinii in patient samples. In contrast, quantification of fungal
      numbers in in vitro setups still largely relies on more conventional procedures
      such as histological stainings. These are time consuming and their applications
      are limited when dealing with small fungal numbers contaminated with tissue and
      cellular debris. This study presents a sensitive and rapid method for P. carinii
      quantification based on PCR analysis that can be easily integrated into standard
      detection procedures without requiring any major additional steps. P. carinii
      specific PCR performed with total DNA extracted from both standard samples with
      known fungal numbers and experimental samples was quantified relative to PCR
      products of a standard concentration from a control plasmid added prior to DNA
      extraction. This measure controlled for variations in DNA extraction and PCR
      efficiency among the samples to be compared. The correlation between analyzed P.
      carinii-specific DNA and the actual fungal numbers employed was highly
      significant.

PMID- 10955954
TI  - HLA and beta-myosin heavy chain do not influence susceptibility to Chagas disease
      cardiomyopathy.
AB  - An inflammatory dilated cardiomyopathy occurs in 30% of Chagas' disease patients,
      chronically infected by Trypanosoma cruzi, while the remaining infected
      individuals are asymptomatic. Studies have indicated a role for genetic factors
      in the susceptibility to Chagas' disease cardiomyopathy. In an attempt to
      identify the genetic factors influencing the development and outcome of Chagas'
      cardiomyopathy, we compared the frequencies of alleles from two candidate gene
      loci, class II HLA and a microsatellite marker for the human cardiac beta-myosin
      heavy chain gene in different clinical groups. Patients were grouped as
      asymptomatic or with severe or mild cardiomyopathy. The results indicate that the
      HLA and myosin microsatellite allele profiles in all cardiomyopathy and in
      asymptomatic groups are similar. In conclusion, these results establish that
      polymorphism of HLA-DR and -DQ molecules, as well as beta-cardiac myosin, do not
      influence the susceptibility to different clinical forms of Chagas' disease or
      the progression to severe Chagas' cardiomyopathy. On the other hand, male sex was
      identified as a risk factor for progression to the more severe forms of
      cardiomyopathy (relative risk = 8.75).

PMID- 10955955
TI  - Differential cytokine mRNA expression in Dermatophagoides farinae allergen
      sensitized and respiratory syncytial virus-infected mice.
AB  - The interaction between mite allergen sensitization and respiratory syncytial
      virus (RSV) infection at the level of cytokine mRNA expression was examined in a
      murine model in the present study. Primary RSV infection enhances expression of
      inflammatory cytokines such as IL-6, IFN-gamma, and eotaxin in the lung and
      upregulates the expression of Th2-like cytokines IL-10 and IL-13 in the spleen in
      BALB/c mice. Mite antigen-sensitized and RSV-infected (ASRSV) mice show enhanced
      (P < 0.05) total serum IgE compared to antigen-sensitized mice. However, the
      levels of viral mRNA in the lung tissues are comparable between RSV-infected and
      ASRSV mice. It is concluded that compartmentalization of cytokine expression
      following RSV infection plays a role in the augmentation of Th2-like and IgE
      antibody response to RSV.

PMID- 10955956
TI  - Phage infection of the obligate intracellular bacterium, Chlamydia psittaci
      strain guinea pig inclusion conjunctivitis.
AB  - The infectious cycle of phiCPG1, a bacteriophage that infects the obligate
      intracellular pathogen, Chlamydia psittaci strain Guinea Pig Inclusion
      Conjunctivitis, was observed using transmission electron microscopy of phage
      hyperinfected, Chlamydia-infected HeLa cells. Phage attachment to extracellular,
      metabolically dormant, infectious elementary bodies and cointernalisation are
      demonstrated. Following entry, phage infection takes place as soon as elementary
      bodies differentiate into metabolically active reticulate bodies. Phage-infected
      bacteria follow an altered developmental path whereby cell division is inhibited,
      producing abnormally large reticulate bodies, termed maxi-reticulate bodies,
      which do not mature to elementary bodies. These forms eventually lyse late in the
      chlamydial developmental cycle, releasing abundant phage progeny in the inclusion
      and, upon lysis of the inclusion membrane, into the cytosol of the host cell.
      Structural integrity of the hyperinfected HeLa cell is markedly compromised at
      late stages. Released phage particles attach avidly to the outer leaflet of the
      outer membranes of lysed and unlysed Chlamydiae at different stages of
      development, suggesting the presence of specific phage receptors in the outer
      membrane uniformly during the chlamydial developmental cycle. A mechanism for
      phage infection is proposed, whereby phage gains access to replicating chlamydiae
      by attaching to the infectious elementary body, subsequently subverting the
      chlamydial developmental cycle to its own replicative needs. The implications of
      phage infection in the context of chlamydial infection and disease are discussed.

PMID- 10955957
TI  - Activity of cecropin P1 and FA-LL-37 against urogenital microflora.
AB  - Two mammalian antimicrobial peptides, FA-LL-37 and cecropin P1, were tested for
      activity against six uropathogens and five Lactobacillus strains by broth
      microdilution assay. Both peptides inhibited Escherichia coli at 25 microM (FA-LL
      39), and 1.56 microM (cecropin P1), Pseudomonas aeruginosa (12.5 microM, and 25
      microM), and Klebsiella pneumoniae, (50 microM, and 1.56 microM), but not
      Enterococcus faecalis and Staphylococcus epidermidis. FA-LL-37 acted
      bacteriocidally against E. coli and bacteriostatically against the other two Gram
      negative organisms. Cecropin P1 was bacteriocidal to all susceptible bacteria.
      Lactobacilli were resistant to both peptides, with the exception of poultry
      isolate Lactobacillus fermentum B-54, which was susceptible to FA-LL-37 at 100
      microM. The differential activities of these peptides toward Gram-negative
      uropathogens versus urogenital lactobacilli demonstrate their potential as a
      topical treatment for urinary tract infections. In addition, production of such
      peptides in vivo could be a natural mechanism to aid in the maintenance of the
      lactobacilli-dominated urogenital flora at the expense of pathogens.

PMID- 10955958
TI  - Recombinant human thrombomodulin(csa+): a tool for analyzing Plasmodium
      falciparum adhesion to chondroitin-4-sulfate.
AB  - The proteoglycan thrombomodulin has been shown to be involved, via its
      chondroitin-sulfate moiety, in the cytoadhesion of chondroitin-4-sulfate-binding
      Plasmodium falciparum-infected erythrocytes to endothelial cells and
      syncytiotrophoblasts. We cloned and expressed in CHO and COS-7 cells a gene
      encoding soluble human recombinant thrombomodulin, with a chondroitin-4-sulfate
      moiety. This system is complementary to the in vitro cell models currently used
      to study the chondroitin-4-sulfate-binding phenotype. It also provides a means of
      overcoming the lack of specificity observed in interactions of infected
      erythrocytes with modified chondroitin-4-sulfate. This thrombomodulin displayed
      normal activity in coagulation, indicating that it was in a functional
      conformation. The recombinant protein, whether produced in CHO or COS-7 cells,
      inhibited cytoadhesion to Saimiri brain microvascular endothelial cells 1D
      infected with Palo-Alto(FUP)1 parasites selected for chondroitin-4-sulfate
      receptor preference. Thus, the recombinant protein was produced with a
      chondroitin-sulfate moiety, identified as a chondroitin-4-sulfate, in both cell
      types. In both cases, the recombinant protein bound to the chondroitin-4-sulfate
      phenotype, but not to CD36- and ICAM-1-binding parasites. The chondroitin-4
      sulfate was 36 kDa in size for CHO and 17.5 kDa for COS-7 cells. There was,
      however, no difference in the capacities of the recombinant proteins produced by
      the two cell types to inhibit the cytoadhesion of infected erythrocytes.
      Thrombomodulin immobilized on plastic or coupled to Dynabeads was used to purify
      specifically the infected erythrocytes that bind to chondroitin-4-sulfate. These
      infected erythrocytes were cultured to establish parasite lines of this
      phenotype. We then showed that the thrombomodulin, labeled with FITC, could be
      used to detect this phenotype in blood samples. Finally, the direct binding of
      infected erythrocytes to immobilized thrombomodulin was used to screen for anti
      chondroitin-4-sulfate-binding antibodies.

PMID- 10955959
TI  - Introduction: dialogue with invaders from extracellular space.

PMID- 10955960
TI  - Signaling and invasin-promoted uptake via integrin receptors.
AB  - The invasin protein encoded by enteropathogenic Yersinia allows entry of bacteria
      into intestinal M cells by binding to integrin receptors. In cultured cells,
      invasin-mediated uptake requires proteins involved in endocytosis and signaling
      to the cell cytoskeleton. At least four different factors have been demonstrated
      to play a role in regulating the efficiency of invasin-promoted uptake. These
      include receptor-ligand affinity, receptor clustering, signaling through focal
      adhesion kinase, and stimulation of cytoskeletal rearrangements by small GTP
      binding proteins.

PMID- 10955961
TI  - Interactions between Listeria monocytogenes and host mammalian cells.
AB  - Bacterial pathogens have developed a variety of strategies to induce their own
      internalization into mammalian cells which are normally nonphagocytic. The Gram
      positive bacterium Listeria monocytogenes enters into many cultured cell types
      using two bacterial surface proteins, InlA (internalin) and InlB. In both cases,
      entry takes place after engagement of a receptor and induction of a series of
      signaling events.

PMID- 10955962
TI  - Diversion of cytoskeletal processes by Shigella during invasion of epithelial
      cells.
AB  - Shigella, the causative agent of bacillar dysentery, invades colonic epithelial
      cells and moves intracellularly to spread from cell to cell. The processes of
      Shigella entry, determined by the Ipa proteins, and of actin-based motility,
      dependent on the IcsA/VirG protein, represent different levels of bacterial
      manipulation of the cell cytoskeleton.

PMID- 10955964
TI  - Invasion and intracellular trafficking of Brucella abortus in nonphagocytic
      cells.
AB  - Brucella abortus is a facultative intracellular parasite that promotes its own
      internalization in nonphagocytic cells. The bacterium initially interacts with
      compartments of the early endocytic cascade, then rapidly segregates from this
      intracellular pathway and associates with the autophagocytic cascade. During the
      late stages of infection, Brucella proliferates within the endoplasmic reticulum
      of host cells.

PMID- 10955963
TI  - Do pathogenic neisseriae need several ways to modify the host cell cytoskeleton?
AB  - Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens which have
      to interact with mucosa and/or cellular barriers for their life cycle. Even
      though they both give rise to dramatically different diseases, most of the
      mechanisms mediating cellular interactions are common to N. meningitidis and N.
      gonorrhoeae. This suggests that bacterial cell interactions may be essential not
      only for pathogenesis but also for other aspects of the bacterial life cycle that
      are common to both N. meningitidis and N. gonorrhoeae. Opacity proteins and pili
      are two major components identified as transducing signals to host cells, thus
      leading to cytoskeleton modifications. This manuscript will review the recent
      developments concerning the mechanisms mediating cellular interactions of
      pathogenic Neisseria and will tentatively put them into the perspective of
      pathogenesis and bacterial life cycle.

PMID- 10955965
TI  - Small GTP binding proteins and bacterial virulence.
AB  - Many bacterial toxins and bacterial enzymes modify small GTPases. Toxins exhibit
      different enzymatic activities on either the switch 1 or switch 2 domains of
      these small GTPases leading to inactivation or activation of such intracellular
      timer molecules. In addition, some virulence factors of certain invasive bacteria
      such as Salmonella also modulate small GTP binding proteins either by mimicking
      GTPase exchange factors or GTPase activating proteins.

PMID- 10955966
TI  - Eliciting the practitioner within.

PMID- 10955967
TI  - The hurt of pain, the threat of suffering.

PMID- 10955968
TI  - Sepsis and life stress.

PMID- 10955969
TI  - Loving openness as a meta-world hypothesis: expanding our vision of mind and
      medicine.
AB  - In 1942, Stephen C. Pepper published a seminal book, World Hypothesis, that
      sought to explain how people create hypotheses about the world. Pepper proposed
      that there were four basic world hypotheses: (1) formistic (the hypothesis that
      nature exists as categories); (2) mechanistic (the hypothesis that nature obeys
      cause-effect relationships); (3) contextual (the hypothesis that processes in
      nature are relative and context dependent); and (4) organismic (the hypothesis
      that processes in nature reflect interactive relationships in systems). Most
      classical and modern theories of science and medicine implicitly adopt one or
      more of these foundational hypotheses. In 1997, Schwartz and Russek proposed that
      there were four additional world hypotheses: (5) implicit process (the hypothesis
      that nature consists of invisible forces and information, such as energy and
      consciousness); (6) circular causality (the hypothesis that nature consists of
      circulating interactions that inherently change over time); (7) creative
      unfolding (the hypothesis that processes in nature reflect flexible designs or
      plans that have adaptive function); and (8) integrative diversity (the hypothesis
      that phenomena in nature reflect complex integrations of diverse processes).
      Theories in postmodern and integrative science implicitly adopt hypotheses 5
      through 8. However, underlying the creation of the eight world hypotheses is an
      implicit meta-world hypothesis which we term loving openness (the hypothesis that
      phenomena in nature reflect levels of openness and caring). This paper briefly
      explains the origin and implications of the loving openness meta-world hypothesis
      for understanding mind-body healing in medicine, the reordering of values in
      integrative medicine (with a primary focus on caring with humility), and the
      fostering of a new vision for twenty-first century frontier science,
      spirituality, and medicine.

PMID- 10955970
TI  - In defense of reason: a meta-response to loving openness.

PMID- 10955971
TI  - Loving openness and the healing relationship.

PMID- 10955972
TI  - Some epistemological questions about world hypotheses, loving openness, truth,
      and one medicine.

PMID- 10955973
TI  - Integrative medicine, loving openness, and the need for wisdom.

PMID- 10955974
TI  - Techniques to comfort children during stressful procedures.
AB  - Medical procedures can be unpleasant experiences for children, their parents, and
      health care providers. We present this model of working with children having
      invasive procedures with the aim of helping to increase the comfort of infants
      and children and also parents and medical staff. The model has five parts: (1)
      Preparing the child and parent for the procedure and for their role during the
      procedure; (2) inviting the parent/caregiver to be present; (3) utilizing the
      treatment room for stressful procedures; (4) positioning the child in a
      comforting manner; and (5) maintaining a calm, positive atmosphere.

PMID- 10955975
TI  - Medical psychological observations during the Holocaust: escape into health.

PMID- 10955976
TI  - Courage and yielding in the Holocaust.

PMID- 10955977
TI  - Comments on the "science of symptoms" and the experience of stress.

PMID- 10955978
TI  - An outsider's commentary.

PMID- 10955979
TI  - Secrets kept from the mind but not from the body.

PMID- 10955980
TI  - Giardiasis surveillance--United States, 1992-1997.
AB  - PROBLEM/CONDITION: Giardia intestinalis, the organism that causes the
      gastrointestinal illness giardiasis, is the most commonly diagnosed intestinal
      parasite in public health laboratories in the United States. In 1992, the Council
      of State and Territorial Epidemiologists assigned giardiasis an event code that
      enabled states to begin voluntarily reporting surveillance data on giardiasis to
      CDC. REPORTING PERIOD: This report includes data that were reported from January
      1992 through December 1997. DESCRIPTION OF THE SYSTEM: The National Giardiasis
      Surveillance System includes data about reported cases of giardiasis from
      participating states. Because most states were already collecting data on
      occurrence of giardiasis, the assignment of an event code to giardiasis has
      allowed voluntary reporting of these data to CDC via the National Electronic
      Telecommunications System for Surveillance. RESULTS: Since 1992, the number of
      states reporting cases of giardiasis to CDC has risen from 23 to 43. The annual
      number of giardiasis cases reported has ranged from 12,793 in 1992 to 27,778 in
      1996. In 1997, cases per 100,000 state population ranged from 0.9 to 42.3, with
      10 states reporting >20.0 cases per 100,000 population and a national average of
      9.5 cases per 100,000 population. In 1997, New York State, including New York
      City, reported the highest number of cases (3,673, or 20.3 cases per 100,000
      population), accounting for 14.5% of cases nationally; however, Vermont reported
      the highest incidence rate in 1997 (42.3 cases per 100,000 population). Both
      states have active surveillance systems in place for giardiasis. Cases have an
      approximately equal sex distribution. Nationally, rates were the highest among
      children aged 0-5 years, followed closely by persons aged 31-40 years. In these
      two age groups, most cases were reported during late summer and early fall--an
      indication that transmission occurred during the summer. INTERPRETATION: This
      report documents the first nationwide look at epidemiologic parameters and
      disease burden estimates for giardiasis in the United States. Transmission occurs
      in all major geographic areas of the country. The seasonal peak in age-specific
      case reports coincides with the summer recreational water season and might
      reflect the heavy use by young children of communal swimming venues (e.g., lakes,
      rivers, swimming pools, and water parks)--a finding consistent with Giardia's low
      infectious dose, the high prevalence of diaper-aged children in swimming venues,
      the extended periods of cyst shedding that can occur, and Giardia's environmental
      resistance. Estimates based on state surveillance data indicate that as many as
      2.5 million cases of giardiasis occur annually in the United States. PUBLIC
      HEALTH ACTION: Giardiasis surveillance provides data to educate public health
      practitioners and health-care providers about the scope and magnitude of
      giardiasis in the United States. These data can be used to establish research
      priorities and to plan future prevention efforts.

PMID- 10955981
TI  - Nickel-catalyzed intermolecular domino reactions.
AB  - Nickel-catalyzed multiple-component reactions are a promising new type of domino
      reaction. For instance, a variety of starting materials such as alkenes, alkynes,
      and unsaturated carbonyl compounds can be connected with high selectivity under
      reasonably mild conditions. These reactions provide a new route to synthetically
      important key compounds including dienes, enynes, enol silyl ethers, and
      carbocycles. Furthermore, an asymmetric version of the reaction is successful.
      Thus, intermolecular domino reactions should be important reactions for years to
      come.

PMID- 10955982
TI  - Scanning tunneling microscopy: a unique tool in the study of chirality, dynamics,
      and reactivity in physisorbed organic monolayers.
AB  - Scanning tunneling microscopy (STM) is applied to study organic monolayers,
      physisorbed at the liquid-graphite interface. Due to the very local nature of the
      probing, the structure of these adlayers has been imaged with very high detail.
      The high resolution allowed us to investigate the effect of molecular chirality
      on the monolayer formation and provided a unique way to study chemical reactions
      at the liquid-graphite interface. Making use of a fast scanning mode, dynamic
      processes in these adlayers have been visualized.

PMID- 10955983
TI  - Crystallographic structure determination of unstable species.
AB  - Crystal structures of reactive short-lived species, as occurring during chemical
      reactions, can be determined through time-resolved crystallography or trapping
      approaches. Prerequisite is the initiation and characterization of the reaction
      in the crystal. Ways to do this, recent results, caveats, and future prospects
      are discussed.

PMID- 10955984
TI  - Co(III)-alkylperoxo complexes: syntheses, structure-reactivity correlations, and
      use in the oxidation of hydrocarbons.
AB  - Crystalline [LCo(III)-OOR] complexes with strong-field ligands, L, afford ROO(*)
      and RO(*) radicals upon mild heating in solution. This fact allows oxidation of
      hydrocarbons by these complexes under mild conditions. The extent of hydrocarbon
      oxidation by discrete [LCo(III)-OOR] complexes depends on the nature of L, the
      solvent, the temperature, and the presence of other M(II) ions. Such systems are
      catalytic in the presence of excess ROOH.

PMID- 10955985
TI  - Soluble polymer-supported organic synthesis.
AB  - Soluble polymers have been used as supports for reagent/catalyst immobilization
      and synthesis. Two polymers are commonly used in this context, linear polystyrene
      and poly(ethylene glycol). The complementary solubility properties of these
      polymers allow access to a wide range of chemistries. Parallel and combinatorial
      libraries of small molecules have been prepared using these polymers, and
      reagents/catalysts that are easily recovered and recycled have been immobilized
      on them. To develop soluble polymers with novel properties, bifunctional
      polymerization initiators have been used in a parallel combinatorial methodology
      to prepare block copolymers that exhibit unique solubility profiles.

PMID- 10955986
TI  - Atomistic modeling of enantioselective binding.
AB  - This Account focuses on computational studies related to chiral recognition. It
      begins with a description of potential energy surfaces and the computational
      tools used to explore such surfaces, describes approximations and assumptions
      made by researchers computing enantioselective binding, and then explains why
      differential free energies of binding can be computed so accurately. The review
      focuses on chiral recognition in chromatography, emphasizing binding and
      enantiodiscriminating forces responsible for chiral recognition. The Account also
      describes computational studies of chiral recognition in cyclodextrins, proteins,
      and synthetic receptors.

PMID- 10955987
TI  - Laser photochemistry of molecular oxygen.
AB  - Molecular oxygen poses very difficult challenges in molecular photochemistry due
      to the extreme weakness of its ultraviolet absorption spectrum. In the past few
      years a new technique called velocity map imaging has been able to overcome many
      of the experimental obstacles to the study of this all-important atmospheric
      species. In this Account several aspects of laser photochemistry of O(2) will be
      described, including the unraveling of the Herzberg and Schumann-Runge continua
      using velocity map imaging.

PMID- 10955988
TI  - Optimal control of molecular motion: design, implementation, and inversion.
AB  - This paper reviews recent theoretical and experimental developments aimed at
      controlling molecular motion using tailored laser fields. Emphasis is given to
      seeking optimal designs for the laser controls and optimal implementation of the
      controls in the laboratory. Optimization on both counts provides a rigorous,
      flexible, and physically attractive means for obtaining the best possible control
      over molecular motion under any specified conditions. The theoretical design and
      laboratory implementation of control are best effected by a closed-loop process
      that draws on observations of the evolving molecular sample to steer it toward
      the desired target. Going beyond control, similar closed-loop laboratory learning
      concepts may lead to automated molecular monitors for inversion to systematically
      identify details of molecular Hamiltonians.

PMID- 10955989
TI  - Unusual catalytic triad of Escherichia coli outer membrane phospholipase A.
AB  - Escherichia coli outer membrane phospholipase A (OMPLA) is an integral membrane
      enzyme. OMPLA is active as a homodimer and requires calcium as a cofactor. The
      crystal structures of the monomeric and the inhibited dimeric enzymes were
      recently determined [Snijder, H. J., et al. (1999) Nature 401, 717-721] and
      revealed that OMPLA monomers are folded into a 12-stranded antiparallel beta
      barrel. The active site consists of previously identified essential residues
      Ser144 and His142 in an arrangement resembling the corresponding residues of a
      serine hydrolase catalytic triad. However, instead of an Asp or Glu that normally
      is present in the triad of serine hydrolases, a neutral asparagine (Asn156) was
      found in OMPLA. In this paper, the importance of the catalytic Asn156 is
      addressed by site-directed mutagenesis studies. All variants were purified at a
      30 mg scale, and were shown to be properly folded using SDS-PAGE and circular
      dichroism spectroscopy. Using chemical cross-linking, it was shown that all
      variants were not affected in their calcium-dependent dimerization properties.
      The Asn156Asp variant exhibited a 2-fold lower activity than wild-type OMPLA at
      neutral pH. Interestingly, the activity of the variant is 1 order of magnitude
      higher than that of the wild type at pH >10. Modest residual activities (5 and
      2.5%, respectively) were obtained for the Asn156Ala and Asn156Gln mutants,
      showing that the active site of OMPLA is more tolerant toward replacements of
      this third residue of the catalytic triad than other serine hydrolases, and that
      the serine and histidine residues are minimally required for catalysis. In the X
      ray structure of dimeric OMPLA, the cofactor calcium is coordinating the putative
      oxyanion via two water molecules. We propose that this may lessen the importance
      for the asparagine in the catalytic triad of OMPLA.

PMID- 10955990
TI  - Ti(IV) uptake and release by human serum transferrin and recognition of Ti(IV)
      transferrin by cancer cells: understanding the mechanism of action of the
      anticancer drug titanocene dichloride.
AB  - The organometallic anticancer agent titanocene dichloride, Cp(2)TiCl(2), is now
      in phase II clinical trials as an anticancer drug, but its mechanism of action is
      poorly understood. We show here that the interactions of Cp(2)TiCl(2) with human
      serum transferrin (hTF) and that of Ti(2)-hTF with adenosine triphosphate (ATP)
      have characteristics that could allow transferrin to act as a mediator for
      titanium delivery to tumor cells. Such reactions may therefore be important to
      the anticancer activity of this new class of drugs. Cp(2)TiCl(2) reacts rapidly
      with human apo-transferrin under physiological conditions (100 mM NaCl, 25 mM
      bicarbonate, and 4 mM phosphate, pH 7.4) with carbonate as a synergistic anion.
      The Cp ligands are released from the drug. Two-dimensional [(1)H, (13)C] NMR
      studies of epsilon-[(13)C]Met-hTF show that Ti(IV) loads the C-lobe first
      followed by the N-lobe and binds in the specific Fe(III) sites. The protein
      conformational changes induced by Ti(IV) appear to be similar to those induced by
      Fe(III). Carbonate can act as a synergistic anion in Ti(2)-hTF but does not
      appear to be essential. A specific Ti(IV)-hTF adduct is formed even in the
      absence of bicarbonate. When the pH of Ti(2)-hTF solutions is lowered, no Ti(IV)
      is released at the endosomal pH of ca. 5.0-5.5, but one Ti(IV) dissociates
      between pH 4.5-2.0. In contrast, in the presence of 1 mM ATP, all Ti(IV) is
      readily released from both lobes when the pH is lowered from 7.0 to 4.5.
      Moreover, Fe(III) displaces Ti(IV) rapidly from the C-lobe of Ti(2)-hTF (<5 min)
      but only slowly (days) from the N-lobe. Thus, the species Fe(C)Ti(N)-hTF might
      also provide a route for Ti(IV) entry into tumor cells via the transferrin
      receptor. Ti(2)-hTF effectively blocked cell uptake of radiolabeled (59)Fe-hTF
      into BeWo cells, a human placental choriocarcinoma cell line in culture. These
      results imply that titanium transferrin might be recognized by the transferrin
      receptor and be taken up into cancer cells.

PMID- 10955991
TI  - Parallel-stranded DNA with mixed AT/GC composition: role of trans G.C base pairs
      in sequence dependent helical stability.
AB  - Parallel-stranded (ps) DNAs with mixed AT/GC content comprising G.C pairs in a
      varying sequence context have been investigated. Oligonucleotides were devised
      consisting of two 10-nt strands complementary either in a parallel or in an
      antiparallel orientation and joined via nonnucleotide linkers so as to form 10-bp
      ps or aps hairpins. A predominance of intramolecular hairpins over intermolecular
      duplexes was achieved by choice of experimental conditions and verified by
      fluorescence determinations yielding estimations of rotational relaxation times
      and fractional base pairing. A multistate mode of ps hairpin melting was revealed
      by temperature gradient gel electrophoresis (TGGE). The thermal stability of the
      ps hairpins with mixed AT/GC content depends strongly on the specific sequence in
      a manner peculiar to the ps double helix. The thermodynamic effects of
      incorporating trans G.C base pairs into an AT sequence are context-dependent: an
      isolated G. C base pair destabilizes the duplex whereas a block of > or =2
      consecutive G.C base pairs exerts a stabilizing effect. A multistate
      heterogeneous zipper model for the thermal denaturation of the hairpins was
      derived and used in a global minimization procedure to compute the thermodynamic
      parameters of the ps hairpins from experimental melting data. In 0.1 M LiCl at 3
      degrees C, the formation of a trans G.C pair in a GG/CC sequence context is
      approximately 3 kJ mol(-)(1) more favorable than the formation of a trans A.T
      pair in an AT/TA sequence context. However, GC/AT contacts contribute a
      substantial unfavorable free energy difference of approximately 2 kJ mol(-)(1).
      As a consequence, the base composition and fractional distribution of isolated
      and clustered G.C base pairs determine the overall stability of ps-DNA with mixed
      AT/GC sequences. Thus, the stability of ps-DNA comprising successive > or =2 G.C
      base pairs is greater than that of ps-DNA with an alternating AT sequence,
      whereas increasing the number of AT/GC contacts by isolating G.C base pairs
      exerts a destabilizing effect on the ps duplex. Molecular modeling of the various
      helices by force field techniques provides insight into the structural basis for
      these distinctions.

PMID- 10955993
TI  - Role of arginine 277 in (S)-mandelate dehydrogenase from Pseudomonas putida in
      substrate binding and transition state stabilization.
AB  - (S)-Mandelate dehydrogenase from Pseudomonas putida is an FMN-dependent alpha
      hydroxy acid dehydrogenase. Structural studies of two homologous enzymes,
      glycolate oxidase and flavocytochrome b(2), indicated that a conserved arginine
      residue (R277 in MDH) interacts with the product carboxylate group [Lindqvist,
      Y., Branden, C.-I., Mathews, F. S., and Lederer, F. (1991) J. Biol. Chem. 266,
      3198-3207]. The catalytic role of R277 was investigated by site-specific
      mutagenesis together with chemical rescue experiments. The R277K, R277G, R277H,
      and R277L proteins were generated and purified in active forms. The k(cat) for
      the charge-conserved mutation, R277K, was only 4-fold lower than wt-MDH, but its
      K(m) value was 40-fold lower; in contrast, k(cat)s for R277G, R277H, and R277L
      were 400-1000-fold lower than for wt-MDH and K(m) values were 5-15-fold lower
      compared to R277K. The K(d)s for negatively charged competitive inhibitors were
      relatively unaffected in all four R277 mutants. The k(cat) for R277G could be
      enhanced by the addition of exogenous guanidines or imidazoles; the maximum
      rescued k(cat) was approximately 70% of the wt-MDH value. Only reagents that were
      positively charged and could function as hydrogen bond donors were effective
      rescue agents. Our results indicate that R277 plays a major role in transition
      state stabilization through its positive charge-consistent with a mechanism
      involving a carbanion intermediate. The positive charge has a relatively small
      contribution toward substrate binding. R277 also forms a specific hydrogen bond
      with both the substrate and the transition state; this interaction contributes
      significantly to the low K(m) for (S)-mandelate.

PMID- 10955992
TI  - Cooperative ordering in homeodomain-DNA recognition: solution structure and
      dynamics of the MATa1 homeodomain.
AB  - The mating type homeodomain proteins, MATa1 and MATalpha2, combine to form a
      heterodimer to bind DNA in diploid yeast cells. The a1-alpha2 heterodimer tightly
      and specifically binds haploid-specific gene operators to repress transcription.
      On its own, however, the a1 homeodomain does not bind DNA in a sequence-specific
      manner. To help understand this interaction, we describe the solution structure
      and backbone dynamics of the free a1 homeodomain. Free a1 in solution is an
      ensemble of structures having flexible hinges at the two turns in the small
      protein fold. Conformational changes in the a1 homeodomain upon ternary complex
      formation are located in the loop between helix 1 and helix 2, where the C
      terminal tail of alpha2 binds to form the heterodimer, and at the C-terminus of
      helix 3, the DNA recognition helix. The observed differences, comparing the free
      and bound a1 structures, suggest a mechanism linking van der Waals stacking
      changes to the ordering of a final turn in the DNA-binding helix of a1. The tail
      of alpha2 induces changes in loop 1 of a1 that push it toward a properly folded
      DNA binding conformation.

PMID- 10955994
TI  - Refinement of the geometry of the retinal binding pocket in dark-adapted
      bacteriorhodopsin by heteronuclear solid-state NMR distance measurements.
AB  - The bacterial proton pump bacteriorhodopsin (BR) is a 26.5 kDa seven
      transmembrane helical protein. Several structural models have been published at >
      or =1.55 A resolution. The initial cis-trans isomerization of the retinal moiety
      involves structural changes within <1 A. To understand the chromophore-protein
      interactions that are important for light-driven proton transport, very accurate
      measurements of the protein geometry are required. To reveal more structural
      details at the site of the retinal, we have, therefore, selectively labeled the
      tryptophan side chains of BR with (15)N and metabolically incorporated retinal,
      (13)C-labeled at position 14 or 15. Using these samples, heteronuclear distances
      were measured with high accuracy using SFAM REDOR magic angle spinning solid
      state NMR spectroscopy in dark-adapted bacteriorhodopsin. This NMR technique is
      applied for the first time to a high-molecular mass protein. Two retinal
      conformers are distinguished by their different isotropic 14-(13)C chemical
      shifts. Whereas the C14 position of 13-cis-15-syn-retinal is 4.2 A from [indole
      (15)N]Trp86, this distance is 3.9 A in the all-trans-15-anti conformer. This
      latter distance allows us to check on the details of the active center of BR in
      the various published models derived from X-ray and electron diffraction data.
      The experimental approach and the results reported in this paper enforce the
      notion that distances between residues of a membrane protein binding pocket and a
      bound ligand can be determined at subangstrom resolution.

PMID- 10955995
TI  - Role of electrostatic interactions in SH2 domain recognition: salt-dependence of
      tyrosyl-phosphorylated peptide binding to the tandem SH2 domain of the Syk kinase
      and the single SH2 domain of the Src kinase.
AB  - SH2 domains are small protein domains that bind specifically to tyrosyl
      phosphorylated sequences. Because phosphorylation contributes a large part of the
      binding free energy, it has been postulated that electrostatic interactions may
      play an important role in SH2 domain recognition. To test this hypothesis, we
      have examined the salt dependence of the interaction between tyrosyl
      phosphorylated peptides and SH2 domains. The dependence of the binding constant,
      K(obs), on [NaCl] was shown to be strong for binding of the tandem SH2 domain of
      the Syk kinase (Syk-tSH2) to doubly phosphorylated peptides derived from immune
      receptor tyrosine activation motifs (dpITAMs): the slopes of plots of log(K(obs))
      versus log [NaCl], designated SK(obs), ranged from -2.6 +/- 0.1 to -3.1 +/- 0.2.
      Binding of the single SH2 domain of the Src kinase to its consensus singly
      phosphorylated peptide (sequence pYEEI where pY indicates a phosphotyrosine) was
      also highly dependent on [NaCl] with a SK(obs) value of -2.4 +/- 0.1. The ability
      of salt to disrupt the interactions between Syk-tSH2 and dpITAM peptides was
      shown to be anion-dependent with the inhibitory effect following the order:
      phosphate > Cl(-) > F(-). For the Syk-tSH2 system, interactions in the pY-binding
      pockets were shown to be responsible for a large portion of the total salt
      dependence: removal of either phosphate from the dpITAM peptide reduced the
      magnitude of SK(obs) by 40-60% and weakened binding by 2-3 orders of magnitude.
      Consistent with this finding, binding of the single amino acid Ac-pY-NH(2) was
      characterized by a large salt dependence of binding and was also dependent on the
      identity of the perturbing anion. The role of peptide residues C-terminal to the
      pY, which are implicated in determining the specificity of the phosphopeptide-SH2
      domain interaction, was next probed by comparing the binding of the Src SH2
      domain to a peptide containing the pYEEI sequence with that of a lower affinity
      variant pYAAI peptide: the magnitude of SK(obs) for the variant peptide was
      reduced to -1.3 +/- 0.1 as compared to -2.4 +/- 0.1 for the pYEEI peptide,
      indicating that in addition to pY, residues conferring peptide binding
      specificity contribute significantly to the salt dependence of SH2 domain
      binding. This study shows that electrostatic interactions play important roles
      not only in mediating pY recognition and binding but also in contributing to the
      specificity of the interactions between tyrosyl phosphopeptides and SH2 domains.

PMID- 10955996
TI  - Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A -
      inhibitor-induced conformational changes.
AB  - D-Cysteine differs from the antiarthritis drug D-penicillamine by only two methyl
      groups on the beta-carbon yet inhibits carboxypeptidase A (CPD) by a distinct
      mechanism: D-cysteine binds tightly to the active site zinc, while D
      penicillamine catalyzes metal removal. To investigate the structural basis for
      this difference, we solved the crystal structure of carboxypeptidase A complexed
      with D-cysteine (D-Cys) at 1.75-A resolution. D-Cys binds the active site zinc
      with a sulfur ligand and forms additional interactions with surrounding side
      chains of the enzyme. The structure explains the difference in potency between D
      Cys and L-Cys and provides insight into the mechanism of D-penicillamine
      inhibition. D-Cys binding induces a concerted motion of the side chains around
      the zinc ion, similar to that found in other carboxypeptidase-inhibitor crystal
      structures and along a limited path. Analysis of concerted motions of CPD and CPD
      inhibitor crystal structures reveals a clustering of these structures into
      distinct groups. Using the restricted conformational flexibility of a drug target
      in this type of analysis could greatly enhance efficiency in drug design.

PMID- 10955997
TI  - Oxidative modification of nucleoside diphosphate kinase and its identification by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Nucleoside diphosphate kinase (NDPK, Nm23) has been implicated as a
      multifunctional protein. However, the regulatory mechanism of NDPK is poorly
      understood. We have examined the modification of NDPK in oxidative stresses. We
      found that oxidative stresses including diamide and H(2)O(2) treatment cause
      disulfide cross-linking of NDPK inside cells. This cross-linking was reversible
      in response to mild oxidative stress, and irreversible to strong stress. This
      suggests that disulfide cross-linked NDPK may be a possible mechanism in the
      modification of cellular regulation. To confirm this idea, oxidative modification
      of NDPK has been performed in vitro using purified human NDPK H(2)O(2)
      inactivated the nucleoside diphosphate (NDP) kinase activity of NDPK by producing
      intermolecular disulfide bonds. Disulfide cross-linking of NDPK also dissociated
      the native hexameric structure into a dimeric form. The oxidation sites were
      identified by the analysis of tryptic peptides of oxidized NDPK, using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). Intermolecular cross-linking between Cys109-Cys109, which is highly possible
      based on the X-ray crystal structure of NDPK-A, and oxidations of four methionine
      residues were identified in H(2)O(2)-treated NDPK. This cross-linkng was
      confirmed using mutant C109A (NDPK-A(C109A)) which had similar enzymatic activity
      as a wild NDPK-A. Mutant NDPK-A(C109A) was not cross-linked and was not easily
      denatured by the oxidant. Therefore, enzymatic activity and the quaternary
      structure of NDPK appear to be regulated by cross-linking with oxidant. These
      findings suggest one of the regulatory mechanisms of NDPK in various cellular
      processes.

PMID- 10955998
TI  - A single engineered point mutation in the adenine glycosylase MutY confers
      bifunctional glycosylase/AP lyase activity.
AB  - The E. coli adenine glycosylase MutY is a member of the base excision repair
      (BER) superfamily of DNA repair enzymes. MutY plays an important role in
      preventing mutations caused by 7, 8-dihydro-8-oxo-2'-deoxyguanosine (OG) by
      removing adenine from OG:A base pairs. Some enzymes of the BER superfamily
      catalyze a strand scission even concomitant with base removal. These bifunctional
      glycosylase/AP lyases bear a conserved lysine group in the active site region,
      which is believed to be the species performing the initial nucleophilic attack at
      C1' in the catalysis of base removal. Monofunctional glycosylases such as MutY
      are thought to perform this C1' nucleophilic displacement by a base-activated
      water molecule, and, indeed, the conservation of amine functionality positioning
      has not been observed in protein sequence alignments. Bifunctional glycosylase/AP
      lyase activity was successfully engineered into MutY by replacing serine 120 with
      lysine. MutY S120K is capable of catalyzing DNA strand scission at a rate
      equivalent to that of adenine excision for both G:A and OG:A mispair substrates.
      The extent of DNA backbone cleavage is independent of treating reaction aliquots
      with 0.1 M NaOH. Importantly, the replacement of the serine with lysine results
      in a catalytic rate that is compromised by at least 20-fold. The reduced
      efficiency in the glycosylase activity is also reflected in a reduced ability of
      S120K MutY to prevent DNA mutations in vivo. These results illustrate that the
      mechanisms of action of the two classes of these enzymes are quite similar, such
      that a single amino acid change is sufficient, in the case of MutY, to convert a
      monofunctional glycosylase to a bifunctional glycosylase/AP lyase.

PMID- 10955999
TI  - Plant succinic semialdehyde dehydrogenase: dissection of nucleotide binding by
      surface plasmon resonance and fluorescence spectroscopy.
AB  - Recent kinetic studies revealed distinct modes of inhibition of mitochondrial
      Arabidopsis thaliana succinic semialdehyde dehydrogenase (At-SSADH1) by AMP and
      ATP. Inhibition of SSADH by ATP may represent an important mechanism of feedback
      regulation of the GABA shunt by the respiratory chain. Here we used two
      approaches to investigate the interaction of ATP with At-SSADH1. Cofactor
      displacement studies based on the reduced fluorescence intensity of free NADH
      versus that of enzyme-bound NADH revealed that both AMP and ATP decreased NADH-At
      SSADH1 complex formation. The competitive inhibitor AMP displaced all bound NADH,
      while ATP, a noncompetitive inhibitor, could not, even in great excess, release
      all NADH from its binding site. To assess the effect of ATP on NAD-At-SSADH, we
      employed surface plasmon resonance to monitor nucleotide binding to immobilized
      At-SSADH1. For this, we used a Strep-tag II modified derivative of At-SSADH1
      (designated ST-At-SSADH1). The tagged enzyme was tightly and reversibly captured
      by StrepTactin, which was covalently immobilized on a CM5 chip. The binding
      constants for NAD(+) and ATP were determined from titration curves and were in
      good agreement with the constants obtained from enzyme kinetics. Surface plasmon
      resonance measurements confirmed that ATP binds to a site different from the
      binding site for NAD(+). GTP competed with ATP. However, only ATP increased the
      dissociation constant of NAD(+) from SSADH. This explains the reduced affinity of
      NAD(+)/NADH to At-SSADH1 in the presence of ATP, as revealed by enzymatic
      kinetics, and supports our model of feedback regulation of SSADH and the GABA
      shunt by ATP.

PMID- 10956000
TI  - Kinetics and equilibria in ligand binding by nitrophorins 1-4: evidence for
      stabilization of a nitric oxide-ferriheme complex through a ligand-induced
      conformational trap.
AB  - Nitrophorins 1-4 (NP1-4) are ferriheme proteins from the blood-sucking insect
      Rhodnius prolixus that transport nitric oxide (NO) to the victim, sequester
      histamine, and inhibit blood coagulation. Here, we report kinetic and
      thermodynamic analyses for ligand binding by all four proteins and their
      reduction potentials. All four undergo biphasic association and dissociation
      reactions with NO. The initial association is fast (1.5-33 microM(-)(1) s(-)(1))
      and similar to that of elephant metmyoglobin. However, unlike in metmyoglobin, a
      slower second phase follows ( approximately 50 s(-)(1)), and the stabilized final
      complexes are resistant to autoreduction (E degrees = +3 to +154 mV vs normal
      hydrogen electrode). NO dissociation begins with a slow, pH-dependent step (0.02
      1.4 s(-)(1)), followed by a faster phase that is again similar to that of
      metmyoglobin (3-52 s(-)(1)). The equilibrium dissociation constants are quite
      small (1-850 nM). NP1 and NP4 display larger release rate constants and smaller
      association rate constants than NP2 and NP3, leading to values for K(d) that are
      about 10-fold greater. The results are discussed in light of the recent crystal
      structures of NP1, NP2, and NP4, which display open, polar distal pockets, and of
      NP4-NO, which displays an NO-induced conformational change that leads to
      expulsion of solvent and complete burial of the NO ligand in a now nonpolar
      distal pocket. Taken together, the results suggest that tighter NO binding in the
      nitrophorins is due to the trapping of the molecule in a nonpolar distal pocket
      rather than through formation of particularly strong Fe-NO or hydrogen bonds.

PMID- 10956001
TI  - Cytochrome c peroxidase-cytochrome c complex: locating the second binding domain
      on cytochrome c peroxidase with site-directed mutagenesis.
AB  - Cytochrome c peroxidase (CcP) can bind as many as two cytochrome c (Cc) molecules
      in an electrostatic complex. The location of the two binding domains on CcP has
      been probed by photoinduced interprotein electron transfer (ET) between zinc
      substituted horse cytochrome c (ZnCc) and CcP with surface charge-reversal
      mutations and by isothermal titration calorimetry (ITC). These results, which are
      the first experimental evidence for the location of domain 2, indicate that the
      weak-binding domain includes residues 146-150 on CcP. CcP(E290K) has a charge
      reversal mutation in the tight-binding domain, which should weaken binding, and
      it weakens the 1:1 complex; K(1) decreases 20-fold at 18 mM ionic strength. We
      have employed two mutations to probe the proposed location for the weak-binding
      domain on the CcP surface: (i) D148K, a "detrimental" mutation with a net (+2)
      change in the charge of CcP, and (ii) K149E, a "beneficial" mutation with a net (
      2) change in the charge. The interactions between FeCc and CcP(WT and K149E) also
      have been studied with ITC. The CcP(D148K) mutation causes no substantial change
      in the 2:1 binding but an increase in the reactivity of the 2:1 complex. The
      latter can be interpreted as a long-range influence on the heme environment or,
      more likely, the enhancement of a minority subset of binding conformations with
      favorable pathways for ET. CcP(K149E) has a charge-reversal mutation in the weak
      binding domain that produces a substantial increase in the 2:1 binding constant
      as measured by both quenching and ITC. For the 1:1 complex of CcP(WT), DeltaG(1)
      = -8.2 kcal/mol (K(1) = 1.3 x 10(6) M(-)(1)), DeltaH(1) = +2.7 kcal/mol, and
      DeltaS(1) = +37 cal/K.mol at 293 K; for the second binding stage, K(2) < 5 x
      10(3) M(-)(1), but accurate thermodynamic parameters were not obtained. For the
      1:1 complex of CcP(K149E), DeltaG(1) = -8.5 kcal/mol (K(1) = 2 x 10(6) M(-)(1)),
      DeltaH(1) = +2. 0 kcal/mol, and DeltaS(1) = +36 cal/K.mol; for the second stage,
      DeltaG(2) = -5.5 kcal/mol (K(1) = 1.3 x 10(4) M(-)(1)), DeltaH(2) = +2.9
      kcal/mol, and DeltaS(2) = +29 cal/K.mol.

PMID- 10956002
TI  - Synergistic inhibitor binding to Streptococcus pneumoniae 5-enolpyruvylshikimate
      3-phosphate synthase with both monovalent cations and substrate.
AB  - The inhibitor binding synergy mechanism of the bi-substrate enzyme Streptococcus
      pneumoniae 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) has been
      investigated with a linkage thermodynamics strategy, involving direct binding
      experiments of one ligand conducted over a range of concentration of the other.
      The results demonstrate that binding of the inhibitor glyphosate (GLP) is highly
      synergistic with both a natural substrate shikimate-3-phosphate (S3P) and
      activating monovalent cations. The synergy between GLP and S3P binding was
      determined to be 1600-fold and is in qualitative agreement with previous work on
      Escherichia coli EPSPS. The binding molar ratios of S3P and GLP were measured as
      1.0 and 0.7 per EPSPS, respectively. Monovalent cations that have been shown
      previously to stimulate S. pneumoniae EPSPS catalytic activity and its inhibition
      by GLP were found here to exhibit a similar rank-order with respect to their
      measured GLP binding synergies (ranging from 0 to > or =3000-fold increase in GLP
      affinity). The cation specificity and the sub-millimolar concentrations where
      these effects occur strongly suggest the presence of a specific cation binding
      site. Analytical ultracentrifugation data ruled out GLP-binding synergy
      mechanisms that derive from, or are influenced by, changes in oligomerization of
      S. pneumoniae EPSPS. Rather, the data are most consistent with an allosteric
      mechanism involving changes in tertiary structure. The results provide a
      quantitative framework for understanding the inhibitor binding synergies in S.
      pneumoniae EPSPS and implicate the presence of a specific cation binding
      regulatory site. The findings will help to guide rational design of novel
      antibiotics targeting bacterial EPSPS enzymes.

PMID- 10956003
TI  - Importance of phosphatidylethanolamine for the interaction of apocytochrome c
      with model membranes containing phosphatidylserine.
AB  - The effect of phosphatidylethanolamine (PE) on the binding of apocytochrome c to
      model membranes was examined. When 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) of the standard vesicles composed of 80% of this lipid and
      20% of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS) was gradually
      replaced with upward of 50% of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine (POPE), the binding increased appreciably. Ca(2+), causing
      the phase separation of PS, also brought about increased binding of apocytochrome
      c in the PC/PS system, underlining the importance of PS properties in membranes
      for the protein binding. The resonance energy transfer between Trp-59 in
      apocytochrome c and pyrene-PS incorporated into bilayers showed that the
      replacement of PC with PE increased the extent of apocytochrome c penetration
      into membranes by a PE concentration-dependent manner. However, in the absence of
      PS, PE had no apparent effect on these functions of apocytochrome c, suggesting
      that PE-induced change(s) of acidic membrane properties is important to the
      association of apocytochrome c with vesicles. From the observations that the
      excimer to monomer fluorescence ratio of pyrene-PS increased and the fluorescence
      of NBD-PS was quenched with increasing concentration of PE, it was deduced that
      PE caused PS-enriched domains in PC/PE/PS membranes. The colocalization of pyrene
      PS with BODIPY-PS by PE further supported the possibility. We suggest that PE
      induced formation of PS-enriched domains acts as binding sites for apocytochrome
      c in membranes.

PMID- 10956004
TI  - Relocation of internal bound water in bacteriorhodopsin during the photoreaction
      of M at low temperatures: an FTIR study.
AB  - Changes in the FTIR difference spectra upon photoconversion of the M intermediate
      to its photoproduct(s) M' were studied in wild-type bacteriorhodopsin and several
      mutants at low temperatures. The studies aimed at examining whether internally
      bound water molecules interact with the chromophore and the key residues Asp85
      and Asp96 in M, and whether these water molecules participate in the
      reprotonation of the Schiff base. We have found that three water molecules are
      perturbed by the isomerization of the chromophore in the M --> M' transition at
      80 K. The perturbation of one water molecule, detected as a bilobe at
      3567(+)/3550(-) cm(-)(1), relaxed in parallel with the relaxation of an Asp85
      perturbation upon increasing temperature from 80 to 100 and 133 K (before the
      reprotonation of the Schiff base). Two water bands of M at 3588 and 3570 cm(-)(1)
      shift to 3640 cm(-)(1) upon photoconversion at 173 K. These bands were attributed
      to water molecules which are located in the vicinity of the Schiff base and Asp85
      (Wat85). In the M to M' transition at 80 and 100 K, where the Schiff base
      remained unprotonated, the Wat85 pair stayed in similar states to those in M. The
      reprotonation of the Schiff base at 133 K occurred without the restoration of the
      Wat85 band around 3640 cm(-)(1). This band was restored at higher temperatures.
      Two water molecules in the region surrounded by Thr46, Asp96, and Phe219 (Wat219)
      were perturbed in the M to M' transition at 80 K and relaxed in parallel with the
      relaxation of the perturbation of Asp96 upon increasing the temperature. Mutant
      studies show that upon photoisomerization of the chromophore at 80 K one of the
      Wat219 water molecules moves closer to Val49 (located near the lysine side chain
      attached to retinal, and close to the Schiff base). These data along with our
      previous results indicate that the water molecules in the cytoplasmic domain
      participate in the connection of Asp96 with the Schiff base and undergo
      displacement during photoconversions, presumably shuttling between the Schiff
      base and a site close to Asp96 in the L to M to N transitions.

PMID- 10956005
TI  - FT-Infrared spectroscopic studies of the iron ligand CO stretch mode of iNOS
      oxygenase domain: effect of arginine and tetrahydrobiopterin.
AB  - The iron ligand CO stretch vibration mode of the inducible nitric oxide synthase
      oxygenase domain (iNOSox) has been studied from 20 to 298 K. iNOSox in the
      absence of arginine reveals a temperature-dependent equilibrium of two major
      conformational substates with CO stretch bands centered at about 1945 and 1954
      cm(-)(1). This behavior is not qualitatively changed when tetrahydrobiopterin
      (H(4)B) is bound. Arginine binding changes significantly the spectrum by
      formation of a sharp CO stretch mode band at about 1905 cm(-)(1) and indicates
      the formation of a hydrogen bond to the CO ligand. For temperatures lower than
      250 K, the stretch vibration frequency decreases almost linearly with decreasing
      temperature and indicates that the coupling between the CO ligand and the
      arginine/protein in the active site via the hydrogen bond is very strong.
      Flashphotolysis of the CO ligand carried out at 25 K revealed the CO stretch mode
      of the photodissociated CO ligand trapped in the heme pocket. There is a negative
      linear relation between the stretch vibration frequencies of the photodissociated
      and the iron-bound CO indicating that the photodissociated ligand stays near the
      heme.

PMID- 10956006
TI  - Oxidation-reduction properties of disulfide-containing proteins of the
      Rhodobacter capsulatus cytochrome c biogenesis system.
AB  - Oxidation-reduction titrations for the active-site disulfide/dithiol couples of
      the helX- and ccl2-encoded proteins involved in cytochrome c biogenesis in the
      purple non-sulfur bacterium Rhodobacter capsulatus have been carried out. The R.
      capsulatus HelX and Ccl2 proteins are predicted to function as part of a
      dithiol/disulfide cascade that reduces a disulfide on the apocytochromes c so
      that two cysteine thiols are available to form thioether linkages between the
      heme prosthetic group and the protein. Oxidation-reduction midpoint potential
      (E(m)) values, at pH 7.0, of -300 +/- 10 and -210 +/- 10 mV were measured for the
      HelX and Ccl2 (a soluble, truncated form of Ccl2) R. capsulatus proteins,
      respectively. Titrations of the disulfide/dithiol couple of a peptide designed to
      serve as a model for R. capsulatus apocytochrome c(2) have also been carried out,
      and an E(m) value of -170 +/- 10 mV was measured for the model peptide at pH 7.0.
      E(m) versus pH plots for HelX, Ccl2, and the apocytochrome c(2) model peptide
      were all linear over the pH range from 5.0 to 8.0, with the -59 mV/pH unit slope
      expected for a reaction in which two protons are taken up for each disulfide that
      is reduced. These results provide thermodynamic support for the proposal that
      HelX reduces Ccl2 and that reduced Ccl2, in turn, serves as the reductant for the
      production of the two thiols of the CysXxxYyyCysHis heme-binding motif of the
      apocytochromes.

PMID- 10956007
TI  - RecA protein promotes strand exchange with DNA substrates containing isoguanine
      and 5-methyl isocytosine.
AB  - The Escherichia coli RecA protein pairs homologous DNA molecules and promotes DNA
      strand exchange in vitro. We have examined DNA strand exchange between a 70
      nucleotide ssDNA fragment and a 40 bp duplex, in which all G and C residues (at
      18 positions distributed throughout the 40 bp exchanged region) were replaced
      with the nonstandard nucleosides 2'-deoxyisoguanosine (iG) and 2'-deoxy-5
      methylisocytidine (MiC), respectively. We demonstrate that the nonstandard
      oligonucleotides are substrates for the RecA protein, permitting DNA strand
      exchange in vitro at a rate and efficiency comparable to exchange with normal DNA
      substrates. This observation provides an expanded experimental basis for
      discussions of potential roles for iG and MiC in a genetic code. Experiments of
      this type also provide another avenue for exploring RecA-facilitated DNA pairing
      mechanisms.

PMID- 10956008
TI  - Two rat surfactant protein A isoforms arise by a novel mechanism that includes
      alternative translation initiation.
AB  - A single gene for rat surfactant protein A (SP-A) encodes two isoforms that are
      distinguished by an isoleucine-lysine-cysteine (IKC) N-terminal extension (SP-A
      and IKC-SP-A). Available evidence suggests that the variants are generated by
      alternative signal peptidase cleavage of the nascent polypeptide at a primary
      site (Cys(-)(1)-Asn(1)) and a secondary site (Gly(-)(4)-Ile(-)(3)). In this
      study, we used site-directed mutagenesis and heterologous expression in vitro and
      in insect cells to the examine mechanisms that may lead to alternative signal
      peptidase cleavage including alternative translation initiation at two in-frame
      AUGs (Met(-)(30) and Met(-)(20)), a suboptimal context for hydrolysis at the
      primary cleavage site, or cotranslational protein modifications that expose an
      otherwise cryptic secondary cleavage site. In vitro translation of a rat cDNA for
      SP-A resulted in both 28 and 29 kDa primary translation products on SDS-PAGE
      analysis, while translation of cDNAs encoding Met-30Ala and Met-20Ala mutations
      resulted in only the single 28 and 29 kDa molecular mass species, respectively.
      These data are consistent with translation initiation at both Met(-)(30) and Met(
      )(20) during in vitro synthesis of SP-A. The Met-30Ala mutation reduced
      expression of the longer isoform in insect cells, indicating that the Met(-)(30)
      site also contributes to eucaryotic protein expression. Forcing translation
      initiation at Met(-)(30) by optimizing the Kozak consensus sequence surrounding
      that codon or by mutating the Met(-)(20) codon resulted in preferential
      expression of the longer SP-A isoform but reduced overall expression of the
      protein almost 10-fold. Both isoforms were generated to some degree whether
      translation was initiated at the codon for Met(-)(30) or Met(-)(20), indicating
      that the site of translation initiation is not the sole determinant of isoform
      generation and suggesting that either the context of the primary cleavage site is
      suboptimal or that cotranslational modifications affect cleavage. Preventing N
      terminal glycosylation at Asn(1) did not affect the site of signal peptidase
      cleavage. Disruption of interchain disulfide formation at Cys(-)(1) by
      substitution with serine markedly enhanced cleavage at the Gly(-)(4)-Ile(-)(3)
      bond, but substitution with alanine enhanced cleavage at the Cys(-)(1)-Asn(1)
      bond. We conclude that rat SP-A isoforms arise by a novel mechanism that includes
      both alternative translation initiation at two in-frame AUGs and a suboptimal
      context for signal peptidase hydrolysis at the primary cleavage site.

PMID- 10956009
TI  - RecA realigns suboptimally paired frames of DNA repeats through a process that
      requires ATP hydrolysis.
AB  - Microsatellite repeats such as mono-, di-, and trinucleotides are highly abundant
      and viable targets for homologous recombination in the genome. However, if
      recombination ensues in such repetitive regions, they are intrinsically prone to
      frame misalignments during pairing and might eventually give rise to genetic
      instabilities. Suboptimally paired frames lead to an abrogation of branch
      migration at the junctions of mixed sequences and repeats, due to a heterologous
      register. If so, can recombination machinery rectify such misalignments in order
      to avoid subsequent arrest in branch migration? We analyzed Escherichia coli
      RecA, the universal prototype of a recombinase, for its pairing abilities across
      repeats. We used a complementary pairing assay to test whether RecA can mediate
      realignments of stochastically paired suboptimal frames to a maximally aligned
      register. Here, we demonstrate that RecA-single stranded DNA filament indeed
      facilitates such a realignment, probably by sliding the paired strands across
      mono- and di- as well as trinucleotide repeats. These realignments apparently
      have no net directional bias. Such a putative "motor" function of RecA seems to
      be ATP hydrolysis-dependent.

PMID- 10956010
TI  - Tri-partite assay for studying exon ligation by the ai5gamma group II intron.
AB  - Group II introns self-splice via a two-step mechanism: cleavage at the 5' splice
      site followed by exon ligation at the 3' splice site. The second step has been
      difficult to study in vitro because it is generally faster than the first. Herein
      we describe development and partial kinetic characterization of a novel assay for
      studying the second step in isolation. In this system, a truncated linear intron
      (nucleotides 1-881) mediates exon ligation between two oligonucleotide
      substrates: a 19 nt 5' exon and a 3' substrate consisting of the last 6
      nucleotides of the intron plus a 6 nucleotide 3' exon. We found that neither the
      exact structure of domain 6 nor the identity of nucleotides flanking the 3'
      splice site is critical for accurate 3' splice site choice by the ai5gamma group
      II intron. The multiple turnover k(cat) (0.14 min(-)(1)) is slower than the
      single turnover k(obs) (0.6-0.7 min(-)(1)), consistent with rate-limiting product
      release under steady-state conditions. Decreased single turnover rates at lower
      pHs were more consistent with loss of catalytic activity than with rate-limiting
      chemistry. Binding of the 3' substrate (K(m) = 2.6 microM) could be improved by
      changing a long-range A:U base pair involving the last intronic nucleotide (the
      gamma-gamma' interaction) to G:C (K(m(3)(')(substrate)) = 1 microM).

PMID- 10956011
TI  - Energy landscape of streptavidin-biotin complexes measured by atomic force
      microscopy.
AB  - The dissociation of ligand and receptor involves multiple transitions between
      intermediate states formed during the unbinding process. In this paper, we
      explored the energy landscape of the streptavidin-biotin interaction by using the
      atomic force microscope (AFM) to measure the unbinding dynamics of individual
      ligand-receptor complexes. The rupture force of the streptavidin-biotin bond
      increased more than 2-fold over a range of loading rates between 100 and 5000
      pN/s. Moreover, the force measurements showed two regimes of loading in the
      streptavidin-biotin force spectrum, revealing the presence of two activation
      barriers in the unbinding process. Parallel experiments carried out with a
      streptavidin mutant (W120F) were used to investigate the molecular determinants
      of the activation barriers. From these experiments, we attributed the outer
      activation barrier in the energy landscape to the molecular interaction of the '3
      4' loop of streptavidin that closes behind biotin.

PMID- 10956012
TI  - Escherichia coli double-strand uracil-DNA glycosylase: involvement in uracil
      mediated DNA base excision repair and stimulation of activity by endonuclease IV.
AB  - Escherichia coli double-strand uracil-DNA glycosylase (Dug) was purified to
      apparent homogeneity as both a native and recombinant protein. The molecular
      weight of recombinant Dug was 18 670, as determined by matrix-assisted laser
      desorption-ionization mass spectrometry. Dug was active on duplex
      oligonucleotides (34-mers) that contained site-specific U.G, U.A, ethenoC.G, and
      ethenoC.A targets; however, activity was not detected on DNA containing a T.G
      mispair or single-stranded DNA containing either a site-specific uracil or
      ethenoC residue. One of the distinctive characteristics of Dug was that the
      purified enzyme excised a near stoichiometric amount of uracil from U.G
      containing oligonucleotide substrate. Electrophoretic mobility shift assays
      revealed that the lack of turnover was the result of strong binding by Dug to the
      reaction product apyrimidinic-site (AP) DNA. Addition of E. coli endonuclease IV
      stimulated Dug activity by enhancing the rate and extent of uracil excision by
      promoting dissociation of Dug from the AP. G-containing 34-mer. Catalytically
      active endonuclease IV was apparently required to mediate Dug turnover, since the
      addition of 5 mM EDTA mitigated the effect. Further support for this
      interpretation came from the observations that Dug preferentially bound 34-mer
      containing an AP.G target, while binding was not observed on a substrate incised
      5' to the AP-site. We also investigated whether Dug could initiate a uracil
      mediated base excision repair pathway in E. coli NR8052 cell extracts using
      M13mp2op14 DNA (form I) containing a site-specific U.G mispair. Analysis of
      reaction products revealed a time dependent appearance of repaired form I DNA;
      addition of purified Dug to the cell extract stimulated the rate of repair.

PMID- 10956013
TI  - Efficient, Mg(2+)-dependent photochemical DNA cleavage by the antitumor
      quinobenzoxazine (S)-A-62176.
AB  - The quinobenzoxazines, a group of structural analogues of the antibacterial
      fluoroquinolones, are topoisomerase II inhibitors that have demonstrated
      promising anticancer activity in mice. It has been proposed that the
      quinobenzoxazines form a 2:2 drug-Mg(2+) self-assembly complex on DNA. The
      quinobenzoxazine (S)-A-62176 is photochemically unstable and undergoes a DNA
      accelerated photochemical reaction to afford a highly fluorescent photoproduct.
      Here we report that the irradiation of both supercoiled DNA and DNA
      oligonucleotides in the presence of (S)-A-62176 results in photochemical cleavage
      of the DNA. The (S)-A-62176-mediated DNA photocleavage reaction requires Mg(2+).
      Photochemical cleavage of supercoiled DNA by (S)-A-62176 is much more efficient
      that the DNA photocleavage reactions of the fluoroquinolones norfloxacin,
      ciprofloxacin, and enoxacin. The photocleavage of supercoiled DNA by (S)-A-62176
      is unaffected by the presence of SOD, catalase, or other reactive oxygen
      scavengers, but is inhibited by deoxygenation. The photochemical cleavage of
      supercoiled DNA is also inhibited by 1 mM KI. Photochemical cleavage of DNA
      oligonucleotides by (S)-A-62176 occurs most extensively at DNA sites bound by
      drug, as determined by DNase I footprinting, and especially at certain G and T
      residues. The nature of the DNA photoproducts, and inhibition studies, indicate
      that the photocleavage reaction occurs by a free radical mechanism initiated by
      abstraction of the 4'- and 1'-hydrogens from the DNA minor groove. These results
      lend further support for the proposed DNA binding model for the quinobenzoxazine
      2:2 drug-Mg(2+) complex and serve to define the position of this complex on the
      minor groove of DNA.

PMID- 10956014
TI  - Binding of Nisin Z to bilayer vesicles as determined with isothermal titration
      calorimetry.
AB  - Nisin Z, a 34-residue lantibiotic, is secreted by some lactic acid bacteria and
      exerts its antibacterial activity against various Gram-positive bacteria by
      permeabilizing the cell membrane. It is a cationic amphiphilic peptide with
      several unusual dehydro residues and thioether-bridged lanthionines. Isothermal
      titration calorimetry was used to provide a quantitative thermodynamic
      description for nisin Z adsorption to and penetration into negatively charged and
      neutral lipid bilayers. The binding of the cationic peptide (electric charge z
      approximately 3.8) to anionic membranes was found to be dominated by
      electrostatic forces which could be described with the Gouy-Chapman theory. For
      biologically relevant conditions with a membrane surface potential of -40 mV, the
      peptide concentration near the membrane surface increases by about 2-3 orders of
      magnitude compared to the bulk concentration. The binding step proper, i.e., the
      transition from the lipid-water interface into the membrane, is almost
      exclusively driven by the high surface concentration. Binding can be described by
      a partition equilibrium of the form X(b) = KC(M) = KC(p,f) exp(
      z(p)psi(0)F(0)/RT), where C(M) is the peptide surface concentration, C(p,f) the
      bulk concentration, and psi(0) the membrane surface potential. The intrinsic
      partition coefficient (K = 1.8 M(-)(1)) is remarkably small, indicating a
      correspondingly small hydrophobic energy contribution to the binding process. The
      electrostatic model was confirmed with nisin Z mutants in which valine-32 was
      replaced with either lysine (V32K) or glutamate (V32E), increasing or decreasing
      the electric charge by 1 unit. The extent of peptide binding increased for V32K
      and decreased for V32E as predicted by the electrostatic theory. In contrast,
      electrostatic effects were almost negligible for the binding of nisin Z to
      neutral membranes. However, the binding isotherms were characterized by a
      distinctly larger intrinsic binding constant K(0) of approximately 540 M(-)(1)
      and an enhanced hydrophobic free energy of binding. The binding of nisin Z to
      sonicated lipid vesicles is exothermic with a DeltaH degrees of ca. -9 and -3.4
      kcal/mol for charged and neutral membranes, respectively.

PMID- 10956015
TI  - Closer proximity between opposing domains of vertebrate calmodulin following
      deletion of Met(145)-Lys(148).
AB  - To investigate the structural linkage between the opposing globular domains in
      vertebrate calmodulin (CaM), we have constructed a CaM mutant (CaMX(145))
      deficient in the last four amino acids between Met(145) and Lys(148) at the
      carboxyl terminal. Circular dichroism and fluorescence spectroscopic measurements
      were used to detect changes in the average secondary and tertiary structure of
      CaMX(145) in comparison to full-length CaM. Complementary measurements of the
      maximal calcium-binding stoichiometry and ability to activate the plasma membrane
      (PM) Ca-ATPase permit an assessment of the functional significance of observed
      structural changes. In comparison with native CaM, we find that CaMX(145)
      exhibits (i) a large reduction in alpha-helical content, (ii) a dramatic decrease
      in the average spatial separation between the opposing globular domains, (iii)
      the loss of one high-affinity calcium-binding site, and (iv) a diminished binding
      affinity for the PM-Ca-ATPase. Thus, the sequence near the carboxyl terminus
      functions to stabilize high-affinity calcium binding at one site and facilitates
      important intramolecular interactions that maintain CaM in an extended
      conformation. However, despite the large conformational changes resulting from
      deletion of the last four amino acids at the carboxyl terminal, CaMX(145) can
      fully activate the PM-Ca-ATPase. These results indicate that target protein
      binding can restore the nativelike structure critical to function, emphasizing
      that the structure of the central helix is not critical to CaM function under
      equilibrium conditions. Rather, the central helix functions to maintain the
      spatial separation between the opposing domains in CaM that may be critical to
      high-affinity binding and the rapid activation of the PM-Ca-ATPase, which are
      necessary for optimal calcium signaling. Thus, following initial association
      between CaM and target proteins, structural changes involving the carboxyl
      terminal sequence have the potential to play an important role in triggering the
      structural collapse of CaM that facilitates the rapid and cooperative binding of
      the opposing globular domains with target proteins, which is important to high
      affinity binding and rapid enzyme activation.

PMID- 10956016
TI  - Nucleoside triphosphate specificity of tubulin.
AB  - We have determined the binding affinity for binding of the four purine nucleoside
      triphosphates GTP, ITP, XTP, and ATP to E-site nucleotide- and nucleoside
      diphosphate kinase-depleted tubulin. The relative binding affinities are 3000 for
      GTP, 10 for ITP, 2 for XTP, and 1 for ATP. Thus, the 2-exocyclic amino group in
      GTP is important in determining the nucleotide specificity of tubulin and may
      interact with a hydrogen bond acceptor group in the protein. The 6-oxo group also
      makes a contribution to the high affinity for GTP. NMR ROESY experiments indicate
      that the four nucleotides have different average conformations in solution. ATP
      and XTP are characterized by a high anti conformation, ITP by a medium anti
      conformation, and GTP by a low anti conformation. Possibly, the preferred
      solution conformation contributes to the differences in affinities. When the
      tubulin E-site is saturated with nucleotide, there appears to be little
      difference in the ability of the four nucleotides to stimulate assembly. The
      critical protein concentration is essentially identical in reactions using the
      four nucleotides. All four of the nucleotides were hydrolyzed during the assembly
      reaction, and the NDPs were incorporated into the microtubule. We also examined
      the binding of two gamma-phosphoryl-modified GTP photoaffinity analogues, p(3)-1,
      4-azidoanilido-GTP and p(3)-1,3-acetylanilido-GTP. These analogues are inhibitors
      of the assembly reaction and bind to tubulin with affinities that are 15- and 50
      fold lower, respectively, than the affinty for GTP. The affinity of GTP is less
      sensitive to substitutions at the gamma-phosphoryl position that to changes in
      the purine ring.

PMID- 10956017
TI  - Contribution of the 30/36 hydrophobic contact at the C-terminus of the alpha
      helix to the stability of the ubiquitin molecule.
AB  - The contribution of the hydrophobic contact in the C-capping motif of the alpha
      helix to the thermodynamic stability of the ubiquitin molecule has been analyzed.
      For this, 16 variants of ubiquitin containing the full combinatorial set of four
      nonpolar residues Val, Ile, Leu, and Phe at C4 (Ile30) and C' ' (Ile36) positions
      were generated. The secondary structure content as estimated using far-UV
      circular dichroism (CD) spectroscopy of all but Phe variants at position 30 did
      not show notable changes upon substitutions. The thermodynamic stability of these
      ubiquitin variants was measured using differential scanning calorimetry, and it
      was shown that all variants have lower stability as measured by decreases in the
      Gibbs energy. Since in some cases the decrease in stability was so dramatic that
      it rendered an unfolded protein, it was therefore concluded that, despite
      apparent preservation of the secondary structure, the 30/36 hydrophobic contact
      is essential for the stability of the ubiquitin molecule. The decrease in the
      Gibbs energy in many cases was found to be accompanied by a large (up to 25%)
      decrease in the enthalpy of unfolding, particularly significant in the variants
      containing Ile to Leu substitutions. This decrease in enthalpy of unfolding is
      proposed to be primarily the result of the perturbed packing interactions in the
      native state of the Ile --> Leu variants. The analysis of these data and
      comparison with effects of similar amino acid substitutions on the stability of
      other model systems suggest that Ile --> Leu substitutions cannot be isoenergetic
      at the buried site.

PMID- 10956018
TI  - The mechanism of pore assembly for a cholesterol-dependent cytolysin: formation
      of a large prepore complex precedes the insertion of the transmembrane beta
      hairpins.
AB  - Perfringolysin O (PFO) is a member of the cholesterol-dependent cytolysin (CDC)
      family of membrane-penetrating toxins. The CDCs form large homooligomers
      (estimated to be comprised of up to 50 CDC monomers) that are responsible for
      generating a large pore in cholesterol-containing membranes of eukaryotic cells.
      The assembly of the PFO cytolytic complex was examined to determine whether it
      forms an oligomeric prepore complex on the membrane prior to the insertion of its
      membrane-spanning beta-sheet. A PFO oligomeric complex was formed on liposomes at
      both 4 degrees C and 37 degrees C and shown by SDS-agarose gel electrophoresis to
      be comprised of a large, comparatively homogeneous complex instead of a
      distribution of oligomer sizes. At low temperature, the processes of
      oligomerization and membrane insertion could be resolved, and PFO was found to
      form an oligomer without significant membrane insertion of its beta-hairpins.
      Furthermore, PFO was found to increase the ion conductivity through a planar
      bilayer by large and discrete stepwise changes in conductance that are consistent
      with the insertion of a preassembled pore complex into the bilayer. The combined
      results of these analyses strongly support the hypothesis that PFO forms a large
      oligomeric prepore complex on the membrane surface prior to the insertion of its
      transmembrane beta-sheet.

PMID- 10956019
TI  - A novel venombin B from agkistrodon contortrix contortrix: evidence for
      recognition properties in the surface around the primary specificity pocket
      different from thrombin.
AB  - A novel thrombin-like enzyme (named contortrixobin) has been purified to
      homogeneity from the venom of Agkistrodon contortrix contortrix by affinity
      chromatography on arginine-Sepharose, anionic exchange chromatography, and HPLC.
      The complete amino acid sequence has been determined by Edman degradation and by
      mass spectral analysis of peptides generated by enzymatic cleavage. A
      microheterogeneity at the level of residue 234 has been detected, as demonstrated
      by peptides differing for the occurrence of Pro234 ( approximately 85%) or Asp234
      ( approximately 15%). Contortrixobin (i) has six disulfide bonds whose sequence
      positions have been determined by mass spectrometry and (ii) does not contain
      carbohydrates in its structure. As expected, the 234 residue sequence of
      contortrixobin exhibits strong homology with snake venom serine proteases acting
      on either fibrinogen or other blood coagulation components. The interaction of
      contortrixobin with chromogenic substrates indicates a higher specificity for
      arginine over lysine in the primary subsite and a faster attack to ester than
      amides. The hydrolytic activity of contortrixobin is strongly inhibited by
      diisopropyl fluorophosphate and to a less extent by phenylmethylsulfonyl
      fluoride, benzamidine, and 4', 6-diamidino-2-phenylindole; hirudin (a specific
      alpha-thrombin inhibitor) as well as basic pancreatic trypsin inhibitor has a
      small effect on contortrixobin's catalytic properties. Contortrixobin (i)
      preferentially releases fibrinopeptide B from human fibrinogen, (ii) activates
      blood coagulation Factors V and XIII with a rate 250-500-fold lower than human
      alpha-thrombin, and (iii) does not induce thrombocyte aggregation,
      intracytoplasmatic calcium ion increase in platelets, and activation of Factor
      VIII. Evidence for biorecognition properties different from thrombin is also
      reported.

PMID- 10956020
TI  - Correlation of beta-amyloid aggregate size and hydrophobicity with decreased
      bilayer fluidity of model membranes.
AB  - beta-amyloid peptide (Abeta) is the primary constituent of senile plaques, a
      defining feature of Alzheimer's disease. Aggregated Abeta is toxic to neurons,
      but the mechanism of toxicity remains unproven. One proposal is that Abeta
      toxicity results from relatively nonspecific Abeta-membrane interactions. We
      hypothesized that Abeta perturbs membrane structure as a function of the
      aggregation state of Abeta. Toward exploring this hypothesis, Abeta aggregate
      size and hydrophobicity were characterized using dynamic and static light
      scattering and 1,1-bis(4-anilino)naphthalene-5,5-disulfonic acid (bis-ANS)
      fluorescence. The effect of Abeta aggregation state on the membrane fluidity of
      unilamellar liposomes was assessed by monitoring the anisotropy of the membrane
      embedded fluorescent dye, 1,6-diphenyl-1,3,5-hexatriene (DPH). Unaggregated Abeta
      at pH 7 did not bind bis-ANS and had little to no effect on membrane fluidity.
      More significantly, Abeta aggregated at pH 6 or 7 decreased membrane fluidity in
      a time- and dose-dependent manner. Aggregation rate and surface hydrophobicity
      were considerably greater for Abeta aggregated at pH 6 than at neutral pH and
      were strongly correlated with the extent of decrease in membrane fluidity.
      Prolonged (7 days) Abeta aggregation resulted in a return to near-baseline levels
      in both bis-ANS fluorescence and DPH anisotropy at pH 7 but not at pH 6. The
      addition of gangliosides to the liposomes significantly increased the DPH
      anisotropy response. Hence, self-association of Abeta monomers into aggregates
      exposes hydrophobic sites and induces a decrease in membrane fluidity. Abeta
      aggregate-induced changes in membrane physical properties may have deleterious
      consequences on cellular functioning.

PMID- 10956021
TI  - Oxidant-induced S-glutathiolation inactivates protein kinase C-alpha (PKC-alpha):
      a potential mechanism of PKC isozyme regulation.
AB  - Protein kinase C (PKC) isozymes are subject to inactivation by reactive oxygen
      species (ROS) through as yet undefined oxidative modifications of the isozyme
      structure. We previously reported that Cys-containing, Arg-rich peptide-substrate
      analogues spontaneously form disulfide-linked complexes with PKC isozymes,
      resulting in isozyme inactivation. This suggested that PKC might be inactivated
      by oxidant-induced S-glutathiolation, i.e., disulfide linkage of the endogenous
      molecule glutathione (GSH) to PKC. Protein S-glutathiolation is a reversible
      oxidative modification that has profound effects on the activity of certain
      enzymes and binding proteins. To directly examine whether PKC could be
      inactivated by S-glutathiolation, we used the thiol-specific oxidant diamide
      because its oxidant activity is restricted to induction of disulfide bridge
      formation. Diamide weakly inactivated purified recombinant cPKC-alpha, and this
      was markedly potentiated to nearly full inactivation by 100 microM GSH, which by
      itself was without effect on cPKC-alpha activity. Diamide inactivation of cPKC
      alpha and its potentiation by GSH were both fully reversed by DTT. Likewise, GSH
      markedly potentiated diamide inactivation of a PKC isozyme mixture purified from
      rat brain (alpha, beta, gamma, epsilon, zeta) in a DTT-reversible manner. GSH
      potentiation of diamide-induced cPKC-alpha inactivation was associated with S
      glutathiolation of the isozyme. cPKC-alpha S-glutathiolation was demonstrated by
      the DTT-reversible incorporation of [(35)S]GSH into the isozyme structure and by
      an associated change in the migration position of cPKC-alpha in nonreducing SDS
      PAGE. Diamide treatment of NIH3T3 cells likewise induced potent, DTT-reversible
      inactivation of cPKC-alpha in association with [(35)S] S-thiolation of the
      isozyme. Taken together, the results indicate that PKC isozymes can be
      oxidatively inactivated by S-thiolation reactions involving endogenous thiols
      such as GSH.

PMID- 10956022
TI  - Membrane binding of peptides containing both basic and aromatic residues.
      Experimental studies with peptides corresponding to the scaffolding region of
      caveolin and the effector region of MARCKS.
AB  - We have studied the binding of peptides containing both basic and aromatic
      residues to phospholipid vesicles. The peptides caveolin(92-101) and MARCKS(151
      175) both contain five aromatic residues, but have 3 and 13 positive charges,
      respectively. Our results show the aromatic residues insert into the bilayer and
      anchor the peptides weakly to vesicles formed from the zwitterionic lipid
      phosphatidylcholine (PC). Incorporation of a monovalent acidic lipid (e.g.,
      phosphatidylserine, PS) into the vesicles enhances the binding of both peptides
      via nonspecific electrostatic interactions. As predicted from application of the
      Poisson-Boltzmann equation to atomic models of the peptide and membranes, the
      enhancement is larger (e.g., 10(4)- vs 10-fold for 17% PS) for the more basic
      MARCKS(151-175). Replacing the five Phe with five Ala residues in MARCKS(151-175)
      decreases the binding to 10:1 PC/PS vesicles only slightly (6-fold). This result
      is also consistent with the predictions of our theoretical model: the loss of the
      attractive hydrophobic energy is partially compensated by a decrease in the
      repulsive Born/desolvation energy as the peptide moves away from the membrane
      surface. Incorporating multivalent phosphatidylinositol 4, 5-bisphosphate
      (PIP(2)) into PC vesicles produces dramatically different effects on the membrane
      binding of the two peptides: 1% PIP(2) enhances caveolin(92-101) binding only 3
      fold, but increases MARCKS(151-175) binding 10(4)-fold. The strong interaction
      between the effector region of MARCKS and PIP(2) has interesting implications for
      the cellular function of MARCKS.

PMID- 10956023
TI  - Rearrangement of L-2-hydroxyglutarate to L-threo-3-methylmalate catalyzed by
      adenosylcobalamin-dependent glutamate mutase.
AB  - Adenosylcobalamin-dependent enzymes catalyze a variety of chemically difficult
      isomerizations in which a nonacidic hydrogen on one carbon is interchanged with
      an electron-withdrawing group on an adjacent carbon. We describe a new
      isomerization, that of L-2-hydroxyglutarate to L-threo-3-methylmalate, involving
      the migration of the carbinol carbon. This reaction is catalyzed by glutamate
      mutase, but k(cat) = 0.05 s(-)(1) is much lower than that for the natural
      substrate, L-glutamate (k(cat) = 5.6 s(-)(1)). EPR spectroscopy confirms that the
      major organic radical that accumulates on the enzyme is the C-4 radical of L-2
      hydroxyglutarate. Pre-steady-state kinetic measurements revealed that L-2
      hydroxyglutarate-induced homolysis of AdoCbl occurs very rapidly, with a rate
      constant approaching those measured previously with glutamate and methylaspartate
      as substrates. These observations are consistent with the rearrangement of the 2
      hydroxyglutaryl radical being the rate-determining step in the reaction. The slow
      rearrangement of the 2-hydroxyglutaryl radical can be attributed to the poor
      stabilization by the hydroxyl group of the migrating glycolyl moiety of the
      radical transiently formed on the migrating carbon. In contrast, with the normal
      substrate the migrating carbon atom bears a nitrogen substituent that better
      stabilizes the analogous glycyl moiety. These studies point to the importance of
      the functional groups attached to the migrating carbon in facilitating the carbon
      skeleton rearrangement.

PMID- 10956024
TI  - Hanging gondola structure of the T1 domain in a voltage-gated K(+) channel.
AB  - The T1 domain is a approximately 100-residue sequence in the cytoplasmic N
      terminal region of K(v)-type K(+) channels. The structure of the isolated domain
      is known, but it is uncertain whether the structure of this domain is maintained
      in the fully assembled, membrane-associated, homotetrameric channel protein. We
      use the structure of the isolated domain as a guide for designing disulfide bonds
      to cross-link Shaker K(+) channels through the T1 domain. Six pairs of residues
      with side chains closely apposed across the T1 subunit interface were selected
      for replacement by cysteine. Of these, three pairs formed cross-links upon air
      oxidation of cysteine-substituted Shaker channels expressed in Xenopus oocyte
      membranes. Two of these cross-linked channels were examined
      electrophysiologically and were found to have gating properties only slightly
      altered from wild-type. The results show that the structure of the isolated T1
      domain exists in the mature ion channel. They also demand that this domain is
      attached to the membrane-embedded part of the protein as a cytoplasmic "hanging
      gondola", and that ions gain access to the pore through four "windows" formed by
      the linker connecting T1 to the channel's first transmembrane helix.

PMID- 10956025
TI  - Analysis of the kinetic and redox properties of the NADH peroxidase R303M mutant:
      correlation with the crystal structure.
AB  - The crystal structure of the flavoprotein NADH peroxidase shows that the Arg303
      side chain forms a hydrogen bond with the active-site His10 imidazole and is
      therefore likely to influence the catalytic mechanism. Dithionite titration of an
      R303M mutant [E(FAD, Cys42-sulfenic acid)] yields a two-electron reduced
      intermediate (EH(2)) with enhanced flavin fluorescence and almost no charge
      transfer absorbance at pH 7.0; the pK(a) for the nascent Cys42-SH is increased by
      over 3.5 units in comparison with the wild-type EH(2) pK(a) of </=4.5. NADH
      titration of the mutant peroxidase yields the same EH(2) intermediate, but in
      contrast to the behavior of wild-type enzyme, this species can be reduced
      directly to an EH(4).NAD(+) complex. Kinetic analyses demonstrate that the R303M
      mutant is severely compromised, although active, with k(cat) = 3 s(-)(1) at pH
      7.0, 5 degrees C; enzyme-monitored turnover results indicate that the steady
      state consists predominantly of an E-FADH(2).NAD(+) species. When the oxidized
      mutant is reacted anaerobically with 0.9 equiv of NADH/FAD, a clearly biphasic
      pattern is observed at 450 nm; relatively rapid flavin reduction is followed by
      reoxidation at 2.6-2.7 s(-)(1) ( approximately k(cat)). Thus replacement of
      Arg303 with Met leads to an altered peroxidase form in which the rate-limiting
      step in turnover is the intramolecular transfer of electrons from FADH(2) -->
      Cys42-SOH. The crystal structure of the R303M peroxidase has been refined at 2.45
      A resolution. In addition to eliminating the Arg303 interactions with His10 and
      Glu14, the mutant exhibits a significant change in the conformation of the Cys42
      SOH side chain relative to FAD and His10 in particular. These and other results
      provide a detailed understanding of Arg303 and its role in the structure and
      mechanism of this unique flavoprotein peroxidase.

PMID- 10956026
TI  - Identification of a thrombin-binding region in the sixth epidermal growth factor
      like repeat of human thrombomodulin.
AB  - The interaction of thrombin with a 28-residue peptide corresponding to the N
      terminal subdomain of the sixth EGF-like repeat of human thrombomodulin plus the
      junction between the fifth and the sixth EGF-like domains was characterized in
      solution by use of NMR spectroscopy, particularly differential resonance
      perturbations and transferred nuclear Overhauser effects (transferred NOEs). The
      EGF-like thrombomodulin fragment, or hTM422-449, is conformationally flexible in
      the absence of thrombin. Upon addition of thrombin, differential resonance
      perturbations and transferred NOEs are observed for the thrombomodulin peptide,
      suggesting specific and rapidly reversible binding and structuring of hTM422-449
      in complex with thrombin. Residue-specific analysis of the differential line
      broadening, resonance shifts, and transferred NOEs identified regions of hTM422
      449 responding to thrombin binding as the N-terminal residues Thr422-Ile424 and
      residues His438-Ile447 corresponding to the central beta-hairpin, or B-loop, of
      the consensus EGF-like repeat. The formation of the beta-hairpin is supported by
      the pattern of transferred NOEs bringing the two beta-strands together and
      characterizing a type I beta-turn. Docking of the thrombomodulin peptide to the
      anion-binding exosite I of thrombin revealed structural details capturing binding
      contacts identified so far as essential for the thrombin-thrombomodulin
      interaction. Definition of specific interactions between thrombin and a minimal
      fragment of the sixth EGF-like domain of human TM may lead to the discovery of
      new peptidomimetic molecules as modulators of blood coagulation.

PMID- 10956027
TI  - Dihydroorotate dehydrogenase from Clostridium oroticum is a class 1B enzyme and
      utilizes a concerted mechanism of catalysis.
AB  - Dihydroorotate dehydrogenase from Clostridium oroticum was purified to apparent
      homogeneity and found to be a heterotetramer consisting of two alpha (32 kDa) and
      two beta (28 kDa) polypeptides. This subunit composition, coupled with known
      cofactor requirements and the ability to transfer electrons from L-dihydroorotate
      to NAD(+), defines the C. oroticum enzyme as a family 1B dihydroorotate
      dehydrogenase. The results of steady-state kinetic analyses and isotope exchange
      studies suggest that this enzyme utilizes a ping-pong steady-state kinetic
      mechanism. The pH-k(cat) profile is bell-shaped with a pK(a) of 6.4 +/- 0.1 for
      the ascending limb and 8. 9 +/- 0.1 for the descending limb; the pH-k(cat)/K(m)
      profile is similar but somewhat more complex. The pK(a) values of 6.4 and 8.9 are
      likely to represent the ionizations of cysteine and lysine residues in the active
      site which act as a general base and an electrostatic catalyst, respectively. At
      saturating levels of NAD(+), the isotope effects on (D)V and (D)(V/K(DHO)),
      obtained upon deuteration at both the C(5)-proR and C(5)-proS positions of L
      dihydroorotate, increase from a value of unity at pH >9.0 to sizable values at
      low pH due to a high commitment to catalysis at high pH. At pH = 6.5, the
      magnitude of the double isotope effects (D)V and (D)(V/K(DHO)), obtained upon
      additional deuteration at C(6), is consistent with a mechanism in which C(5)-proS
      proton transfer and C(6)-hydride transfer occur in a single, partially rate
      limiting step.

PMID- 10956028
TI  - The crystal structure of bacillus cereus phosphonoacetaldehyde hydrolase: insight
      into catalysis of phosphorus bond cleavage and catalytic diversification within
      the HAD enzyme superfamily.
AB  - Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolysis of
      phosphonoacetaldehyde to acetaldehyde and phosphate using Mg(II) as cofactor. The
      reaction proceeds via a novel bicovalent catalytic mechanism in which an active
      site nucleophile abstracts the phosphoryl group from the Schiff-base intermediate
      formed from Lys53 and phosphonoacetaldehyde. In this study, the X-ray crystal
      structure of the Bacillus cereus phosphonatase homodimer complexed with the
      phosphate (product) analogue tungstate (K(i) = 50 microM) and the Mg(II) cofactor
      was determined to 3.0 A resolution with an R(cryst) = 0.248 and R(free) = 0.284.
      Each monomer is made up of an alpha/beta core domain consisting of a centrally
      located six-stranded parallel beta-sheet surrounded by six alpha-helices. Two
      flexible, solvated linkers connect to a small cap domain (residues 21-99) that
      consists of an antiparallel, five-helix bundle. The subunit-subunit interface,
      formed by the symmetrical packing of the two alpha8 helices from the respective
      core domains, is stabilized through the hydrophobic effect derived from the
      desolvation of paired Met171, Trp164, Tyr162, Tyr167, and Tyr176 side chains. The
      active site is located at the domain-domain interface of each subunit. The Schiff
      base forming Lys53 is positioned on the cap domain while tungstate and Mg(II) are
      bound to the core domain. Mg(II) ligands include two oxygens of the tungstate
      ligand, one oxygen of the carboxylates of Asp12 and Asp186, the backbone carbonyl
      oxygen of Ala14, and a water that forms a hydrogen bond with the carboxylate of
      Asp190 and Thr187. The guanidinium group of Arg160 binds tungstate and the
      proposed nucleophile Asp12, which is suitably positioned for in-line attack at
      the tungsten atom. The side chains of the core domain residue Tyr128 and the cap
      domain residues Cys22 and Lys53 are located nearby. The identity of Asp12 as the
      active-site nucleophile was further evidenced by the observed removal of
      catalytic activity resulting from Asp12Ala substitution. The similarity of
      backbone folds observed in phosphonatase and the 2-haloacid dehalogenase of the
      HAD enzyme superfamily indicated common ancestry. Superposition of the two
      structures revealed a conserved active-site scaffold having distinct catalytic
      stations. Analysis of the usage of polar amino acid residues at these stations by
      the dehalogenases, phosphonatases, phosphatases, and phosphomutases of the HAD
      superfamily suggests possible ways in which the active site of an ancient enzyme
      ancestor might have been diversified for catalysis of C-X, P-C, and P-O bond
      cleavage reactions.

PMID- 10956029
TI  - Methyl groups of thymine bases are important for nucleic acid recognition by
      DtxR.
AB  - The expression of diphtheria toxin is controlled by the diphtheria toxin
      repressor (DtxR). Under conditions of high iron concentration, DtxR binds the tox
      operator to inhibit transcription. To study how DNA binding specificity is
      achieved by this repressor, we solved the crystal structure of the nickel(II)
      activated DtxR(C102D) mutant complexed with a 43mer DNA duplex containing the
      DtxR consensus binding sequence. Structural analysis of this complex and
      comparison with a previously determined DtxR(C102D)-Ni(II)-tox operator ternary
      complex revealed unusual van der Waals interactions between Ser37/Pro39 of the
      repressor helix-turn-helix (HTH) motif and the methyl groups of specific thymine
      bases in the consensus binding sequence. Gel mobility shift assays utilizing
      deoxyuridine modified duplex DNA probes proved the importance of these
      interactions: the four methyl groups shown to interact with Ser37/Pro39 in the
      crystal structure contribute a total of 3.4 kcal/mol to binding energy. Thus, in
      addition to making base-specific hydrogen-bonding interactions to the DNA through
      its Gln43 residue, DtxR also recognizes methyl groups at certain positions in the
      DNA sequence with its Ser37 and Pro39 side chains, to achieve binding specificity
      toward its cognate operator sequences.

PMID- 10956030
TI  - Efficient repair of 8-oxo-7,8-dihydrodeoxyguanosine in human and hamster
      xeroderma pigmentosum D cells.
AB  - The repair of the endogenous lesion 8-oxo-7,8-dihydrodeoxyguanosine (8-oxodG) was
      investigated in the nucleotide excision repair mutant xeroderma pigmentosum D
      (XPD), using human normal or transformed XPD fibroblasts and the Chinese hamster
      XPD cell line UV5. In vivo repair of 8-oxodG induced by hydrogen peroxide
      treatment and analyzed by high-performance liquid chromatography/electrochemical
      detection was normal in the XPD mutant fibroblasts XP15PV and GM434, as compared
      to normal human fibroblasts GM970, GM5757, and GM6114. Similar results were
      obtained with the human SV40-transformed XPD mutant cell line GM8207 in
      comparison to the control cell line GM637. Repair of 8-oxodG was even slightly (2
      3-fold) but reproducibly increased in Chinese hamster XPD mutant UV5 cells, as
      compared to parental AA8 cells. This unexpected effect was reversed by
      transfection in UV5 cells of a wild-type XPD cDNA and confirmed in in vitro
      experiments in which a plasmid substrate containing a single 8-oxoG was repaired
      by UV5 cell extracts. The data show that repair of 8-oxodG is normal in XPD
      cells, thus indicating that the neurological complications of XPD patients may
      not be linked to in vivo accumulation of this lesion.

PMID- 10956031
TI  - In vitro induction of H1-H1 histone cross-linking by adenosine diphosphate-ribose
      polymers.
AB  - It is well-known that H1-H1 interactions are very important for the induction of
      30 nm chromatin fiber and that, among all posttranslational modifications,
      poly(ADP-ribosyl)ation is one of those capable of modifying chromatin structure,
      mainly through H1 histone. As this protein can undergo both covalent and
      noncovalent modifications by poly(ADP-ribosyl)ation, our aim was to investigate
      whether and how ADP-ribose polymers, by themselves, are able to affect the
      formation of H1-H1 oligomers, which are normally present in a condensed chromatin
      structure. The results obtained in our in vitro experimental system indicate that
      ADP-ribose polymers are involved in chromatin decondensation. This conclusion was
      reached as the result of two different observations: (a) H1 histone molecules can
      be hosted in clusters on ADP-ribose polymers, as shown by their ability to be
      chemically cross-linked, and (b) H1 histone has a higher affinity for ADP-ribose
      polymers than for DNA; ADP-ribose polymers compete, in fact, with DNA for H1
      histone binding.

PMID- 10956032
TI  - Studies of promoter recognition and start site selection by T7 RNA polymerase
      using a comprehensive collection of promoter variants.
AB  - We have examined the behavior of T7 RNA polymerase (RNAP) at a set of promoter
      variants having all possible single base pair (bp) substitutions. The polymerase
      exhibits an absolute requirement for initiation with a purine and a strong
      preference for initiation with GTP vs ATP. Promoter variants that would require
      initiation at the normal start site (+1) with CTP or UTP result in a shift in
      initiation to +2 (with GTP). However, the choice of start site is little affected
      by base substitutions elsewhere in the initiation region. Furthermore, when the
      initiation region is shifted either one nucleotide (nt) closer or 1 nt further
      away from the binding region, transcription still begins the same distance
      downstream. These results indicate that the sequence around the start site is of
      little importance in start site selection and that initiation is directed a
      minimum distance of 5 nt downstream from the binding region. At promoters that
      initiate with +1 GGG, T7 RNAP synthesizes a ladder of poly(G) products as a
      result of slippage of the transcript on the three C residues in the template
      strand from +1 to +3. At promoter variants in which there is an opportunity to
      form a longer RNA-DNA hybrid, this G-ladder is enhanced and extended. This
      observation is not in agreement with recent suggestions that the RNA-DNA hybrid
      in the initiation complex cannot extend further than 3 bps upstream from the
      active site [Cheetham, G., Jeruzalmi, D., and Steitz, T. A. (1999) Nature 399, 80
      83].

PMID- 10956033
TI  - In vitro replication of primer-templates containing benzo[a]pyrene adducts by
      exonuclease-deficient Escherichia coli DNA polymerase I (Klenow fragment): effect
      of sequence context on lesion bypass.
AB  - The presence of benzo[a]pyrene diol epoxide (B[a]PDE) adducts in DNA is known to
      interfere with DNA replication. Kinetic studies of nucleotide insertion by
      exonuclease-deficient E. coli DNA polymerase I (Klenow fragment) across from
      either the (+)-trans- or the (+)-cis-B[a]P-N(2)-dG adduct in the 5'-CGT-3'
      sequence context indicated that the rate of nucleotide incorporation followed the
      order: dAMP > dGMP > dTMP > dCMP, which did not correlate with the mutational
      spectrum observed for these adducts in this sequence in E. coli (mostly G-->A
      transitions). Interestingly, a kinetic analysis of extension past the adduct
      showed that, unlike other sequences studied, the primer-template was extended
      best when dT was positioned at the 3'-terminus of the primer across from either a
      (+)-trans- or a (+)-cis-B[a]P-N(2)-dG adduct. In contrast, when the (+)-trans
      B[a]P-N(2)-dG adduct was positioned in the 5'-TGC-3' sequence context, which
      gives predominantly G-->T mutations in E. coli, extension was detectable only
      when dA was positioned across from the adduct. These data provide the first in
      vitro evidence that may explain why G-->A transitions, rather than the G-->T
      transversions found in other sequences, are preferred in the 5'-CGT-3' sequence
      in vivo.

PMID- 10956034
TI  - Control of directionality in nonribosomal peptide synthesis: role of the
      condensation domain in preventing misinitiation and timing of epimerization.
AB  - Product assembly by nonribosomal peptide synthetases (NRPS) is initiated by
      starter modules that comprise an adenylation (A) and a peptidyl carrier protein
      (PCP) domain. Elongation modules of NRPS have in addition a condensation (C)
      domain that is located upstream of the A domain. They cannot initiate peptide
      bond formation. To understand the role of domain arrangements and the influence
      of the domains present upstream of the A domains of the elongation modules of
      TycB on the initiation and epimerization activities, we constructed a set of
      proteins derived from the tyrocidine synthetases of Bacillus brevis, which
      represent several N-terminal truncations of TycB and the first module of TycC.
      The latter was fused with the thioesterase domain (Te) to give TycC(1)-CAT-Te and
      to ensure product turnover. TycB(2)(-)(3)-AT.CATE and TycB(3)-ATE, lacking an N
      terminal C domain, were capable of initiating peptide synthesis and epimerizing.
      In contrast, the corresponding constructs with a cognate N-terminal C domain,
      TycB(2)(-)(3)-T.CATE and TycB(3)-CATE, were strongly reduced in initiation and
      epimerization. Evidence is also provided that this reduction is due to substrate
      binding in an enantioselective binding pocket at the acceptor position of the C
      domains. By using TycB(2)(-)(3)-AT.CATE and TycB(3)-ATE, we were able to turn an
      elongation module into an initiation module, and to establish an in-trans system
      for the formation of new di- and tripeptides with recombinant NRPS modules. We
      also show that epimerization domains of elongation modules can in principle
      epimerize both aminoacyl-S-Ppant (TycB(3)-ATE) and peptidyl-S-Ppant (TycB(2)(
      )(3)-AT.CATE) substrates, although the efficiency for epimerizing the noncognate
      aminoacyl-S-Ppant substrates appears to be lowered.

PMID- 10956035
TI  - Studies of RNA cleavage by photolysis of N-hydroxypyridine-2(1H)-thione. A new
      photochemical footprinting method.
AB  - N-Hydroxypyridine-2(1H)-thione (N-HPT) has been studied as a photochemical source
      of hydroxyl radicals for use in photoinitiated nucleic acid footprinting
      experiments. Steady-state photolysis of dilute aqueous solutions of N-HPT at 350
      nm in the presence of a 385 nucleotide (32)P-labeled RNA, the Tetrahymena L-21
      ribozyme, resulted in cleavage of the RNA at nucleotide resolution. No cleavage
      of the RNA occurred in the absence of light or in the absence of N-HPT.
      Photolysis of the analogous pyridine lacking the N-hydroxyl group did not result
      in detectable amounts of RNA cleavage. The addition of RNA to preirradiated
      solutions of N-HPT gave no apparent RNA cleavage products, suggesting that the
      photoproducts of N-HPT do not result in RNA modification. Cleavage of RNA, upon
      photolysis in the presence of N-HPT, occurred in a sequence-independent fashion
      with double-stranded RNA being cleaved as efficiently as single-stranded RNA.
      Based on these observations, we conclude that photochemically generated
      diffusable hydroxyl radicals are responsible for the RNA cleavage. Experiments
      involving the photolysis of N-HPT in the presence of the Tetrahymena ribozyme and
      magnesium showed a magnesium-dependent protection from RNA cleavage due to
      formation of a folded RNA tertiary structure. The locations and amount of
      protection were identical to those observed in footprinting experiments performed
      with other hydroxyl radical sources. The presence of N-HPT had no effect on
      either the rate of folding or the catalytic activity of the folded RNA,
      indicating that this reagent does not disrupt RNA tertiary structure or otherwise
      affect activity. Thus, N-HPT is established as a new reagent for use in
      photoinitiated RNA footprinting experiments.

PMID- 10956036
TI  - Interactions of Escherichia coli replicative helicase PriA protein with single
      stranded DNA.
AB  - Quantitative analyses of the interactions of the Escherichia coli replicative
      helicase PriA protein with a single-stranded DNA have been performed, using the
      thermodynamically rigorous fluorescence titration technique. The analysis of the
      PriA helicase interactions with nonfluorescent, unmodified nucleic acids has been
      performed, using the macromolecular competition titration (MCT) method.
      Thermodynamic studies of the PriA helicase binding to ssDNA oligomers, as well as
      competition studies, show that independently of the type of nucleic acid base, as
      well as the salt concentration, the type of salt in solution, and nucleotide
      cofactors, the PriA helicase binds the ssDNA as a monomer. The enzyme binds the
      ssDNA with significant affinity in the absence of any nucleotide cofactors.
      Moreover, the presence of AMP-PNP diminishes the intrinsic affinity of the PriA
      protein for the ssDNA by a factor approximately 4, while ADP has no detectable
      effect. Analyses of the PriA interactions with different ssDNA oligomers, over a
      large range of nucleic acid concentrations, indicates that the enzyme has a
      single, strong ssDNA-binding site. The intrinsic affinities are salt-dependent.
      The formation of the helicase-ssDNA complexes is accompanied by a net release of
      3-4 ions. The experiments have been performed with ssDNA oligomers encompassing
      the total site size of the helicase-ssDNA complex and with oligomers long enough
      to encompass only the ssDNA-binding site of the enzyme. The obtained results
      indicate that salt dependence of the intrinsic affinity results predominantly, if
      not exclusively, from the interactions of the ssDNA-binding site of the helicase
      with the nucleic acid. There is an anion effect on the studied interactions,
      which suggests that released ions originate from both the protein and the nucleic
      acid. Contrary to the intrinsic affinities, cooperative interactions between
      bound PriA molecules are accompanied by a net uptake of approximately 3 ions. The
      PriA protein shows preferential intrinsic affinity for pyrimidine ssDNA
      oligomers. In our standard conditions (pH 7.0, 10 degrees C, 100 mM NaCl), the
      intrinsic binding constant for the pyrimidine oligomers is approximately 1 order
      of magnitude higher than the intrinsic binding constant for the purine oligomers.
      The significance of these results for the mechanism of action of the PriA
      helicase is discussed.

PMID- 10956037
TI  - Generation of fluorescence quenchers from the triplet states of chlorophylls in
      the major light-harvesting complex II from green plants.
AB  - Laser flash-induced changes of the fluorescence yield were studied in aggregates
      of light-harvesting complex II (LHCII) on a time scale ranging from microseconds
      to seconds. Carotenoid (Car) and chlorophyll (Chl) triplet states, decaying with
      lifetimes of several microseconds and hundreds of microseconds, respectively, are
      responsible for initial light-induced fluorescence quenching via singlet-triplet
      annihilation. In addition, at times ranging from milliseconds to seconds, a slow
      decay of the light-induced fluorescence quenching can be observed, indicating the
      presence of additional quenchers generated by the laser. The generation of the
      quenchers is found to be sensitive to the presence of oxygen. It is proposed that
      long-lived fluorescence quenchers can be generated from Chl triplets that are not
      transferred to Car molecules. The quenchers could be Chl cations or other
      radicals that are produced directly from Chl triplets or via Chl triplet
      sensitized singlet oxygen. Decay of the quenchers takes place on a millisecond to
      second time scale. The decay is slowed by a few orders of magnitude at 77 K
      indicating that structural changes or migration-limited processes are involved in
      the recovery. Fluorescence quenching is not observed for trimers, which is
      explained by a reduction of the quenching domain size compared to that of
      aggregates. This type of fluorescence quenching can operate under very high light
      intensities when Chl triplets start to accumulate in the light-harvesting
      antenna.

PMID- 10956038
TI  - Photosystem II in different parts of the thylakoid membrane: a functional
      comparison between different domains.
AB  - The electron transport properties of photosystem II (PSII) from five different
      domains of the thylakoid membrane were analyzed by flash-induced fluorescence
      kinetics. These domains are the entire grana, the grana core, the margins from
      the grana, the stroma lamellae, and the Y100 fraction (which represent more
      purified stroma lamellae). The two first fractions originate from appressed grana
      membranes and have PSII with a high proportion of O(2)-evolving centers (80-90%)
      and efficient electron transport on the acceptor side. About 30% of the granal
      PSII centers were found in the margin fraction. Two-thirds of those PSII centers
      evolve O(2), but the electron transfer on the acceptor side is slowed. PSII from
      the stroma lamellae was less active. The fraction containing the entire stroma
      has only 43% O(2)-evolving PSII centers and slow electron transfer on the
      acceptor side. In contrast, PSII centers of the Y100 fraction show no O(2)
      evolution and were unable to reduce Q(B). Flash-induced fluorescence decay
      measurements in the presence of DCMU give information about the integrity of the
      donor side of PSII. We were able to distinguish between PSII centers with a
      functional Mn cluster and without any Mn cluster, and PSII centers which undergo
      photoactivation and have a partially assembled Mn cluster. From this analysis, we
      propose the existence of a PSII activity gradient in the thylakoid membrane. The
      gradient is directed from the stroma lamellae, where the Mn cluster is absent or
      inactive, via the margins where photoactivation accelerates, to the grana core
      domain where PSII is fully photoactivated. The photoactivation process correlates
      to the PSII diffusion along the membrane and is initiated in the stroma lamellae
      while the final steps take place in the appressed regions of the grana core. The
      margin domain is seemingly very important in this process.

PMID- 10956039
TI  - Electron transfer between the quinones in the photosynthetic reaction center and
      its coupling to conformational changes.
AB  - The electron transfer between the two quinones Q(A) and Q(B) in the bacterial
      photosynthetic reaction center (bRC) is coupled to a conformational
      rearrangement. Recently, the X-ray structures of the dark-adapted and light
      exposed bRC from Rhodobacter sphaeroides were solved, and the conformational
      changes were characterized structurally. We computed the reaction free energy for
      the electron transfer from to Q(B) in the X-ray structures of the dark-adapted
      and light-exposed bRC from Rb. sphaeroides. The computation was done by applying
      an electrostatic model using the Poisson-Boltzmann equation and Monte Carlo
      sampling. We accounted for possible protonation changes of titratable groups upon
      electron transfer. According to our calculations, the reaction energy of the
      electron transfer from to Q(B) is +157 meV for the dark-adapted and -56 meV for
      the light-exposed X-ray structure; i.e., the electron transfer is energetically
      uphill for the dark-adapted structure and downhill for the light-exposed
      structure. A common interpretation of experimental results is that the electron
      transfer between and Q(B) is either gated or at least influenced by a
      conformational rearrangement: A conformation in which the electron transfer from
      to Q(B) is inactive, identified with the dark-adapted X-ray structure, changes
      into an electron-transfer active conformation, identified with the light-exposed
      X-ray structure. This interpretation agrees with our computational results if one
      assumes that the positive reaction energy for the dark-adapted X-ray structure
      effectively prevents the electron transfer. We found that the strongly coupled
      pair of titratable groups Glu-L212 and Asp-L213 binds about one proton in the
      dark-adapted X-ray structure, where the electron is mainly localized at Q(A), and
      about two protons in the light-exposed structure, where the electron is mainly
      localized at Q(B). This finding agrees with recent experimental and theoretical
      studies. We compare the present results for the bRC from Rb. sphaeroides to our
      recent studies on the bRC from Rhodopseudomonas viridis. We discuss possible
      mechanisms for the gated electron transfer from to Q(B) and relate them to
      theoretical and experimental results.

PMID- 10956040
TI  - Stopped-flow and steady-state study of the diphenolase activity of mushroom
      tyrosinase.
AB  - The reaction of mushroom (Agaricus bisporus) tyrosinase with dioxygen in the
      presence of several o-diphenolic substrates has been studied by steady-state and
      transient-phase kinetics in order to elucidate the rate-limiting step and to
      provide new insights into the mechanism of oxidation of these substrates. A
      kinetic analysis has allowed for the first time the determination of individual
      rate constants for several of the partial reactions that comprise the catalytic
      cycle. Mushroom tyrosinase rapidly reacts with dioxygen with a second-order rate
      constant k(+8) = 2.3 x 10(7) M(-)(1) s(-)(1), which is similar to that reported
      for hemocyanins [(1.3 x 10(6))-(5.7 x 10(7)) M(-)(1) s(-)(1)]. Deoxytyrosinase
      binds dioxygen reversibly at the binuclear Cu(I) site with a dissociation
      constant K(D)(O)()2 = 46.6 microM, which is similar to the value (K(D)(O)()2 = 90
      microM) reported for the binding of dioxygen to Octopus vulgaris deoxyhemocyanin
      [Salvato et al. (1998) Biochemistry 37, 14065-14077]. Transient and steady-state
      kinetics showed that o-diphenols such as 4-tert-butylcatechol react significantly
      faster with mettyrosinase (k(+2) = 9.02 x 10(6) M(-)(1) s(-)(1)) than with
      oxytyrosinase (k(+6) = 5.4 x 10(5) M(-)(1) s(-)(1)). This difference is
      interpreted in terms of differential steric and polar effects that modulate the
      access of o-diphenols to the active site for these two forms of the enzyme. The
      values of k(cat) for several o-diphenols are also consistent with steric and
      polar factors controlling the mobility, orientation, and thence the reactivity of
      substrates at the active site of tyrosinase.

PMID- 10956041
TI  - Resonance Raman studies of the stoichiometric catalytic turnover of a substrate
      stearoyl-acyl carrier protein delta(9) desaturase complex.
AB  - Resonance Raman spectroscopy has been used to study the effects of substrate
      binding (stearoyl-acyl carrier protein, 18:0-ACP) on the diferric centers of
      Ricinus communis 18:0-ACP Delta(9) desaturase. These studies show that complex
      formation produces changes in the frequencies of nu(s)(Fe-O-Fe) and nu(as)(Fe-O
      Fe) consistent with a decrease in the Fe-O-Fe angle from approximately 123
      degrees in the oxo-bridged diferric centers of the as-isolated enzyme to
      approximately 120 degrees in oxo-bridged diferric centers of the complex.
      Analysis of the shifts in nu(s)(Fe-O-Fe) and nu(as)(Fe-O-Fe) as a function of
      18:0-ACP concentration also suggests that 4e(-)-reduced Delta9D containing two
      diferrous centers has a higher affinity for 18:0-ACP than resting Delta9D
      containing two diferric centers. Catalytic turnover of a stoichiometric complex
      of 18:0-ACP and Delta9D was used to investigate whether an O-atom from O(2) would
      be incorporated into a bridging position of the resultant mu-oxo-bridged diferric
      centers during the desaturation reaction. Upon formation of approximately 70%
      yield of 18:1-ACP product in the presence of (18)O(2), no incorporation of an
      (18)O atom into the mu-oxo bridge position was detected. The result with 18:0-ACP
      Delta(9) desaturase differs from that obtained during the tyrosyl radical
      formation reaction of the diiron enzyme ribonucleotide reductase R2 component,
      which proceeds with incorporation of an O-atom from O(2) into the mu-oxo bridge
      of the resting diferric site. The possible implications of these results for the
      O-O bond cleavage reaction and the nature of intermediates formed during Delta9D
      catalysis are discussed.

PMID- 10956042
TI  - Substrate specificity of the loading didomain of the erythromycin polyketide
      synthase.
AB  - The priming of many modular polyketide synthases is catalyzed by a loading
      acyltransferase-acyl carrier protein (AT(L)-ACP(L)) didomain which initiates
      polyketide biosynthesis by transferring a primer unit to the ketosynthase domain
      of the first module. Because the AT(L) domain influences the choice of the
      starter unit incorporated into the polyketide backbone, its specificity is of
      considerable interest. The AT(L)-ACP(L) didomain of the 6-deoxyerythronolide B
      synthase (DEBS) was functionally expressed in Escherichia coli. Coexpression of
      the Sfp phosphopantetheinyl transferase from Bacillus subtilis in E. coli leads
      to efficient posttranslational modification of the ACP(L) domain with a
      phosphopantetheine moiety. Competition experiments were performed with the holo
      protein to determine the relative rates of incorporation of a variety of
      unnatural substrates in the presence of comparable concentrations of labeled
      acetyl-CoA. Our results showed that the loading didomain of DEBS can accept a
      surprisingly broad range of substrates, although it exhibits a preference for
      unbranched alkyl chain substrates over branched alkyl chain, polar, aromatic, and
      charged substrates. In particular, its tolerance toward acetyl- and butyryl-CoA
      is unexpectedly strong. The studies described here present an attractive
      prototype for the expression, analysis, and engineering of acyltransferase
      domains in modular polyketide synthases.

PMID- 10956043
TI  - Transient kinetics and intermediates formed during the electron transfer reaction
      catalyzed by Candida albicans estrogen binding protein.
AB  - The transient kinetics of the reaction of the estrogen binding protein (EBP1)
      from Candida albicans in which hydride is transferred from NADPH to trans-2
      hexenal (HXL) in two half-reactions were analyzed using UV-visible
      spectrophotometric and fluorometric stopped-flow techniques. The simplest model
      of the first half-reaction involves four steps including very rapid, tight
      binding (K(d) </= 50 nM) characterized by loss of NADPH fluorescence, subsequent
      rapid formation of a charge-transfer complex between NADPH and oxidized enzyme
      bound flavin mononucleotide (FMN) cofactor, followed by rate-limiting reduction
      of the FMN, and finally dissociation of the oxidized pyridine nucleotide. The UV
      visible absorbance behavior of this half-reaction is described by two apparent
      phases, with k(f)(obs) = 355 +/- 6 and k(s)(obs) = 3.30 +/- 0.03 s(-)(1), for the
      fast and slow phases, respectively. The reaction has also been evaluated in terms
      of the full, multi-equilibrium reaction scheme, and microscopic rate constants
      that lead to the observed behavior have been determined through convergent
      experimental techniques and computer simulation. Significant intrinsic kinetic
      isotope effects were noted on both the bond cleavage step and the preceding
      formation of the charge-transfer complex. The enzyme is reoxidized by transfer of
      hydride from the FMN to HXL in the second half-reaction that appears to consist
      of substrate binding to form a Michaelis-type complex and the subsequent chemical
      step. Characterization of the reaction in this simple manner allows determination
      of an apparent K(d) = 100 +/- 9 microM for the reduced enzyme.HXL complex.

PMID- 10956044
TI  - Stabilization of a novel enzyme.substrate intermediate in the Y206F mutant of
      Candida albicans EBP1: evidence for acid catalysis.
AB  - EBP1-catalyzed reduction of alpha,beta-unsaturated ketones and aldehydes is
      proposed to proceed via transfer of hydride from the flavin to the beta-position
      of the olefinic bond, concomitant with or followed by uptake of a proton at the
      alpha-position. Structural analysis suggests that this proton is donated from
      Tyr206, and, hence, a protein was constructed in which it was replaced by
      phenylalanine. The mutation results in a slightly less stable protein than the
      wild type that nevertheless retains the fundamental flavin and phenol binding
      properties of EBP1 characterized previously. The pH profile for binding of phenol
      was characterized over the pH range 6.5-9.5 and was found to be simpler than that
      for the wild-type enzyme. Most importantly, a pK(a) of 8.7 that is perturbed to
      9.4 upon binding of phenol to the wild-type enzyme is missing in the mutant,
      allowing assignment of this pK(a) to the Y206 hydroxyl group. Additionally, the
      pK(a) of phenol is further lowered from its value of 10.0 in solution to
      approximately 6.4 in the active site of the mutant, as compared to 7.1 in the
      wild type. Together, these perturbations lead to an increase of approximately 35
      fold in the binding affinity of the mutant for phenol at high pH relative to the
      affinity of the wild-type enzyme. As expected, the mutation has little effect on
      the reductive half-reaction, in which a hydride equivalent is transferred from
      NADPH to the flavin. In contrast, the reduction of trans-2-hexenal by the reduced
      enzyme is significantly affected. The results indicate formation of a previously
      unobserved charge-transfer (CT) complex following formation of the Michaelis
      complex between substrate and reduced enzyme and preceding reduction of the
      substrate, which occurs at a greatly reduced rate (>/=440-fold) relative to wild
      type. Thus, while the oxidative half-reaction with wild-type enzyme is limited by
      the rate of formation of the CT complex, it is the chemical step that is rate
      limiting in the reaction with EBP1:Y206F, consistent with the role of this
      residue as a general acid.

PMID- 10956045
TI  - Characterization of the heme in human cystathionine beta-synthase by X-ray
      absorption and electron paramagnetic resonance spectroscopies.
AB  - Human cystathionine beta-synthase is one of two key enzymes involved in
      intracellular metabolism of homocysteine. It catalyzes a beta-replacement
      reaction in which the thiolate of homocysteine replaces the hydroxyl group of
      serine to give the product, cystathionine. The enzyme is unusual in its
      dependence on two cofactors: pyridoxal phosphate and heme. The requirement for
      pyridoxal phosphate is expected on the basis of the nature of the condensation
      reaction that is catalyzed; however the function of the heme in this protein is
      unknown. We have examined the spectroscopic properties of the heme in order to
      assign the axial ligands provided by the protein. The heme Soret peak of ferric
      cystathionine beta-synthase is at 428 nm and shifts to approximately 395 nm upon
      addition of the thiol chelator, mercuric chloride. This is indicative of 6
      coordinate low-spin heme converting to a 5-coordinate high-spin heme. The enzyme
      as isolated exhibits a rhombic EPR signal with g values of 2.5, 2.3, and 1.86,
      which are similar to those of heme proteins and model complexes with
      imidazole/thiolate ligands. Mercuric chloride treatment of the enzyme results in
      conversion of the rhombic EPR signal to a g = 6 signal, consistent with formation
      of the high-spin ferric heme. The X-ray absorption data reveal that iron in
      ferric cystathionine beta-synthase is 6-coordinate, with 1 high-Z scatterer and 5
      low-Z scatterers. This is consistent with the presence of 5 nitrogens and 1
      sulfur ligand. Together, these data support assignment of the axial ligands as
      cysteinate and imidazole in ferric cystathionine beta-synthase.

PMID- 10956046
TI  - Domain architecture of the heme-independent yeast cystathionine beta-synthase
      provides insights into mechanisms of catalysis and regulation.
AB  - Cystathionine beta-synthase from yeast (Saccharomyces cerevisiae) provides a
      model system for understanding some of the effects of disease-causing mutations
      in the human enzyme. The mutations, which lead to accumulation of L-homocysteine,
      are linked to homocystinuria and cardiovascular diseases. Here we characterize
      the domain architecture of the heme-independent yeast cystathionine beta
      synthase. Our finding that the homogeneous recombinant truncated enzyme (residues
      1-353) is catalytically active and binds pyridoxal phosphate stoichiometrically
      establishes that the N-terminal residues 1-353 compose a catalytic domain.
      Removal of the C-terminal residues 354-507 increases the specific activity and
      alters the steady-state kinetic parameters including the K(d) for pyridoxal
      phosphate, suggesting that the C-terminal residues 354-507 compose a regulatory
      domain. The yeast enzyme, unlike the human enzyme, is not activated by S-adenosyl
      L-methionine. The truncated yeast enzyme is a dimer, whereas the full-length
      enzyme is a mixture of tetramer and octamer, suggesting that the C-terminal
      domain plays a role in the interaction of the subunits to form higher oligomeric
      structures. The N-terminal catalytic domain is more stable and less prone to
      aggregate than full-length enzyme and is thus potentially more suitable for
      structure determination by X-ray crystallography. Comparisons of the yeast and
      human enzymes reveal significant differences in catalytic and regulatory
      properties.

PMID- 10956047
TI  - Interaction of the antitumor drug 9-aminoacridine with guanidinobenzoatase
      studied by spectroscopic methods: a possible tumor marker probe based on the
      fluorescence exciplex emission.
AB  - Fluorescence spectroscopy, surface-enhanced Raman spectroscopy (SERS), and
      analytical centrifugation are applied in this work to study the interaction of
      the antitumor drug 9-aminoacridine (9AA) with a trypsin-like protease,
      guanidinobenzoatase (GB), extracted from an Erlich tumor. As a consequence of
      this interaction, a strong 9AA exciplex emission can be detected at a certain
      drug and enzyme concentration. The 9AA exciplex emission was also studied for 9AA
      interacting with others serin proteases: alpha-chymotrypsin, trypsin, and
      penicillin G-acylase (PGA), as well as with bovine serum albumin (BSA) in order
      to obtain information about the active center of GB. We have found that the
      exciplex 9AA emission may be induced by a ring-stacking interaction between the
      monomeric drug, under the amino form, and an aromatic residue placed in the
      catalytic site of the protein. The results derived from Raman spectroscopy
      corroborate this interaction mechanism, as demonstrated by the existence of
      typical protonated amino 9AA marker bands as well as an important modification of
      the ring vibrations, thus indicating the existence of an interaction through ring
      stacking. The analytical centrifugation technique was applied to study the GB
      association in aqueous solution, demonstrating that the 9AA/GB interaction
      depends on the enzyme quaternary structure. An interaction of 9AA with an
      associate form of GB, which may be the actual enzyme active form, is suggested.

PMID- 10956048
TI  - Assembly of bacteriophage PRD1 spike complex: role of the multidomain protein P5.
AB  - The spike structure of bacteriophage PRD1 is comprised of proteins P2, P5, and
      P31. It resembles the corresponding receptor-binding structure of adenoviruses.
      We show that purified recombinant protein P5 is an elongated (30 x 2.7 nm; R(h) =
      5.5 nm), multidomain trimer which can slowly associate into nonamers. Cleavage of
      the 340 amino acid long P5 with collagenase yields 2 fragments. The larger, 205
      amino acid long C-terminal fragment appears to contain the residues responsible
      for the trimerization of the protein, whereas the smaller N-terminal part
      mediates the interaction of P5 with the pentameric vertex protein P31 (24 x 2.5
      nm, R(h) = 4.2 nm). In addition, the presence of the N-terminal sequence is
      required for the formation of the P5 nonamer. The results presented here suggest
      that P5 and P31 form an elongated adaptor complex at the 5-fold vertexes of the
      virion which anchors the adsorption protein P2 (21 x 2.5 nm; R(h) = 4.1 nm). Our
      results also suggest that the P5 trimer forms a substantial part of the viral
      spike shaft that was previously thought to be composed exclusively of protein P2.

PMID- 10956050
TI  - Role of zinc binding in type A botulinum neurotoxin light chain's toxic
      structure.
AB  - Clostridial neurotoxins are zinc endopeptidases, and each contains one
      Zn(2+)/molecule. To investigate the structural/functional role of Zn(2+) in
      botulinum neurotoxin light chain (the enzymatic subunit of the neurotoxin), the
      effect of the removal of zinc on protein folding and enzyme kinetics was
      investigated. The active site Zn(2+), which was easily displaced from the active
      site by ethylenediaminetetraacetate, reversibly binds to the BoNT/A light chain
      (LC) in a stoichiometric manner. Enzymatic activity was completely abolished in
      the zinc-depleted light chain (apo-LC). However, Zn(2+) replenishment partially
      restored the activity in the re-Zn(2+)-LC (k(cat) = 72 min(-)(1)) compared to the
      holo-LC (k(cat) = 140 min(-)(1)). Comparable K(m) values in the holo- and re
      Zn(2+)-LC were observed (41 and 55 microM, respectively), indicating a similar
      substrate binding ability. We investigated the structural basis of a 3-fold
      difference in the catalytic efficiency of the native holo-LC and re-Zn(2+)-LC by
      analyzing secondary and tertiary structural parameters. Removal of the zinc
      causes irreversible tertiary structural change while the secondary structure
      remains unchanged. Zinc binding leads to enhanced thermal stability of the LC,
      which is not identical in the native holo-LC and re-Zn(2+)-LC.

PMID- 10956049
TI  - Fluorescence spectroscopy of single tryptophan mutants of apolipophorin-III in
      discoidal lipoproteins of dimyristoylphosphatidylcholine.
AB  - The structure of the exchangeable apolipoprotein, apolipophorin-III from Locusta
      migratoria, apoLp-III, is described as a bundle of five amphipathic alpha
      helices. To study the interaction of each of the helices of apoLp-III with a
      lipid surface, we designed five single-Trp mutants, each containing a Trp residue
      in a different alpha-helix. The Trp residues were located in the nonpolar domains
      of the amphipathic alpha-helices. The kinetics of the spontaneous interaction of
      the mutants with dimyristoylphosphatidylcholine (DMPC) indicated that all mutants
      behaved as typical exchangeable apolipoproteins. Circular dichroism in the far-UV
      indicated that all proteins have a high and similar helical content in the lipid
      bound state. The interaction of the Trp residues with the lipid surface was
      investigated in recombinant lipoprotein particles made with DMPC. The properties
      of the Trp residues were investigated by fluorescence spectroscopy. These studies
      showed major changes in the spectroscopic properties of the Trp residues upon
      binding to lipid. These changes are observed with all single-Trp mutants,
      indicating that a major conformational change, which affects the properties of
      all helices, takes place upon binding to lipid. The position of the fluorescence
      maximum, the quenching efficiency of acrylamide as determined by steady-state and
      time-resolved fluorescence, and the fluorescence lifetimes of the single-Trp
      mutants suggest that helices 1, 4, and 5 interact with the nonpolar domains of
      the lipid. The properties of the Trp in helices 2 and 3 suggest that these
      helices adopt a different binding configuration than helices 1, 4, and 5. Helices
      2 and 3 appear to be interacting with the polar headgroups of the phospholipids
      or constitute a different domain that does not interact with the lipid surface.

PMID- 10956051
TI  - Investigations of the oxidative disassembly of Fe-S clusters in Clostridium
      pasteurianum 8Fe ferredoxin using pulsed-protein-film voltammetry.
AB  - Rapid responses of biological [4Fe-4S] clusters to conditions of oxidative stress
      have been studied by protein-film voltammetry by using precise pulses of
      electrode potential to trigger reactions. Investigations with Clostridium
      pasteurianum 8Fe ferredoxin exploit the fact that [3Fe-4S] clusters display a
      characteristic pattern of voltammetric signals, so that their appearance and
      disappearance after an oxidative pulse can be tracked unambiguously under
      electrochemical control. Adsorbed to monolayer coverage at a graphite electrode,
      the protein initially shows a strong signal (B') at -0.36 V vs standard hydrogen
      electrode due to two [4Fe-4S](2+/+) clusters at similar potentials. Short square
      pulses (0.1-5 s) to potentials in the range 0.5-0.9 V cause extensive loss of B',
      and new signals appear (A'and C') that arise from [3Fe-4S] species (+/0 and 0/2-
      couples). The A' and B' intensities quantify transformations which are induced by
      the pulse and which occur subsequently when more reducing conditions are
      restored. Optimal [3Fe-4S] formation (in excess over [4Fe-4S]) is achieved with a
      3-s pulse to 0.7 V, following which there is rapid partial recovery to yield a
      1:1 3Fe:4Fe ratio, consistent with 7Fe protein. Thus, a 6Fe protein is formed,
      but one of the clusters is rapidly repaired. The [3Fe-4S]:[4Fe-4S] ratio follows
      a bell-shaped curve spanning the same potential range that defines complete loss
      of signals, while double-pulse experiments show that [3Fe-4S](+) resists further
      oxidative damage. Oxidative disassembly involves successive one-electron
      oxidations of [4Fe-4S] (i.e., 2+ --> 3+ --> 4+), with [3Fe-4S](+) being a
      relatively stable byproduct, that is, not an intermediate. Disassembly of [3Fe
      4S] in the 7Fe protein continues after reducing conditions are restored, with
      lifetimes depending on oxidation level; thus 1+ (most stable) > 0 > 2-. In the
      presence of Fe(2+), the 0 level is stabilized by conversion back to [4Fe
      4S](2+/+). By pulsing in the presence of Zn(2+), the [3Fe-4S] clusters that are
      formed are trapped rapidly as their Zn adducts.

PMID- 10956052
TI  - Cholesterol efflux to high-density lipoproteins and apolipoprotein A-I
      phosphatidylcholine complexes is inhibited by ethanol: role of apolipoprotein
      structure and cooperative interaction of phosphatidylcholine and cholesterol.
AB  - There is a substantial body of evidence showing that moderate alcohol consumption
      is associated with a reduced risk of cardiovascular morbidity and mortality. One
      of the factors thought to contribute to this reduction in risk is an increase in
      the level of high-density lipoproteins (HDL) correlated with alcohol consumption.
      However, HDL levels are elevated in heavy drinkers, but their risk of vascular
      disease is greater compared with that of moderate drinkers. Ethanol at
      concentrations observed in heavy drinkers and alcoholics may directly act on HDL
      and apolipoproteins and in turn modify cholesterol efflux. In this paper, we show
      that ethanol significantly inhibited cholesterol efflux from fibroblasts to HDL
      and to apolipoprotein A-I (apoA-I) complexed with phosphatidylcholine (PC).
      Ethanol significantly inhibited binding of PC to apoA-I, inhibited incorporation
      of cholesterol only when apoA-I contained PC, and did not alter incorporation of
      cholesterol into HDL. ApoA-I structure was altered by ethanol as monitored by
      steady-state fluorescence polarization of tryptophan residues. The absence of
      ethanol effects on incorporation of cholesterol into HDL versus inhibition of
      cholesterol incorporation into the apoA-I-PC complex suggests that the effects of
      ethanol on cholesterol efflux mediated by HDL involve interaction with the cell
      surface and that efflux mediated by the apoA-I-PC complex is a combination of
      aqueous diffusion and contact with the cell surface. In addition, effects of
      ethanol on apoA-I suggest that pre-beta-HDL or lipid-free apoA-I may be more
      perturbed by ethanol than mature HDL, and such effects may be pathophysiological
      with respect to the process of reverse cholesterol transport in heavy drinkers
      and alcoholics.

PMID- 10956053
TI  - Transducin-dependent protonation of glutamic acid 134 in rhodopsin.
AB  - A highly conserved carboxylic acid residue in rhodopsin, Glu(134), modulates
      transducin (G(t)) interaction. It has been postulated that Glu(134) becomes
      protonated upon receptor activation. We studied the interaction between rhodopsin
      and G(t) using Fourier transform infrared (FTIR) difference spectroscopy combined
      with attenuated total reflection (ATR). Formation of the complex between G(t) and
      photoactivated rhodopsin reconstituted into phosphatidylcholine vesicles caused
      prominent infrared absorption increases at 1641, 1550, and 1517 cm(-)(1). The
      rhodopsin mutant E134Q was also studied. When measured in the presence of G(t),
      replacement of Glu(134) by glutamine abolished the low-frequency part of a broad
      absorption band at 1735 cm(-)(1) that is normally superimposed on the light
      induced absorption changes of Asp(83) and Glu(122) of rhodopsin. In addition, a
      negative absorption band at 1400 cm(-)(1) that is evoked by interaction of native
      metarhodopsin II (MII) with G(t) was not observed in the difference spectrum of
      the E134Q mutant. Thus, Glu(134) is ionized in the dark and exhibits a
      symmetrical COO(-) stretching vibration at 1400 cm(-)(1). Glu(134) becomes
      protonated in the G(t)-MII complex and displays a C=O stretching mode near 1730
      cm(-)(1). The E134Q mutation also affects absorption changes attributable to
      lipids, suggesting that the protonation of Glu(134) is linked to transfer of the
      carboxylic acid side chain from a polar to a nonpolar environment by becoming
      exposed to the lipid phase when G(t) binds. These results show directly that
      Glu(134) becomes protonated in MII upon G(t) binding and suggest that changes in
      receptor conformation affect lipid-protein interactions.

PMID- 10956054
TI  - Mutagenicity of nitroaromatic compounds.

PMID- 10956055
TI  - Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic
      arsenic.
AB  - Monomethylarsonous acid (MMA(III)) has been detected for the first time in the
      urine of some humans exposed to inorganic arsenic in their drinking water. Our
      experiments have dealt with subjects in Romania who have been exposed to 2.8, 29,
      84, or 161 microg of As/L in their drinking water. In the latter two groups,
      MMA(III) was 11 and 7% of the urinary arsenic while the monomethylarsonic acid
      (MMA(V)) was 14 and 13%, respectively. Of our 58 subjects, 17% had MMA(III) in
      their urine. MMA(III) was not found in urine of any members of the group with the
      lowest level of As exposure. If the lowest-level As exposure group is excluded,
      23% of our subjects had MMA(III) in their urine. Our results indicate that (a)
      future studies concerning urinary arsenic profiles of arsenic-exposed humans must
      determine MMA(III) concentrations, (b) previous studies of urinary profiles
      dealing with humans exposed to arsenic need to be re-examined and re-evaluated,
      and (c) since MMA(III) is more toxic than inorganic arsenite, a re-examination is
      needed of the two hypotheses which hold that methylation is a detoxication
      process for inorganic arsenite and that inorganic arsenite is the major cause of
      the toxicity and carcinogenicity of inorganic arsenic.

PMID- 10956056
TI  - Characterization of 4-oxo-2-nonenal as a novel product of lipid peroxidation.
AB  - Fe(II)-mediated decomposition of 13-[S-(Z,E)]-9, 11-hydroperoxyoctadecadienoic
      (hydroperoxylinoleic) acid resulted in the formation of three alpha,beta
      unsaturated aldehydes. At low Fe(II) concentrations or at early time points after
      the addition of Fe(II), two major products were observed. The least polar product
      had chromatographic properties that were identical with those of 4-oxo-2-nonenal.
      Conversion of this product to its bis-oxime derivative with hydroxylamine
      hydrochloride resulted in two syn- and two anti-oxime isomers that had
      chromatographic and mass spectral properties identical with the properties of
      products derived from an authentic standard of 4-oxo-2-nonenal. This confirmed
      for the first time that 4-oxo-2-nonenal is a major product of the Fe(II)-mediated
      breakdown of lipid hydroperoxides. The more polar product had chromatographic
      properties that were similar to those of 4-hydroperoxy-2-nonenal. LC/MS analysis
      of its syn- and anti-oxime isomers confirmed this structural assignment. Thus, 4
      hydroperoxy-2-nonenal is a previously unrecognized major product of lipid
      hydroperoxide decomposition. At high Fe(II) concentrations and at longer
      incubation times, a third more polar product was observed with chromatographic
      properties that were identical to those of 4-hydroxy-2-nonenal. The syn- and anti
      oxime isomers had chromatographic and mass spectral properties identical with the
      properties of products derived from an authentic standard of 4-hydroxy-2-nonenal.
      It appears that 4-hydroperoxy-2-nonenal is formed initially and that it is then
      converted to 4-hydroxy-2-nonenal in the presence of high Fe(II) concentrations or
      by extended incubations in the presence of low Fe(II) concentrations. It is
      conceivable that some of the 4-hydroperoxy-2-nonenal is also converted to 4-oxo-2
      nonenal. However, we cannot rule out the possibility that it is also formed by a
      concerted mechanism from a rearrangement product of 13-[S-(Z,E)]-9, 11
      hydroperoxyoctadecadienoic acid.

PMID- 10956057
TI  - Promutagenic etheno-DNA adducts in multistage mouse skin carcinogenesis:
      correlation with lipoxygenase-catalyzed arachidonic acid metabolism.
AB  - Formation of the lipoxygenase-catalyzed metabolites of arachidonic acid, 8
      hydroxyeicosatetraenoic acid (8-HETE) and 12-hydroxyeicosatetraenoic acid (12
      HETE), and of the exocyclic DNA adducts 1,N(6)-ethenodeoxyadenosine (epsilondA)
      and 3, N(4)-ethenodeoxycytidine (epsilondC) was investigated in NMRI mouse skin
      carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by
      12-O-tetradecanoylphorbol-13-acetate (TPA). In reversible papillomas obtained
      after 20 weeks of TPA treatment, 15- and 68-fold higher contents of 8-HETE and 12
      HETE, respectively, were observed, which were paralleled by 12- and 9-fold
      increased amounts of epsilondA and epsilondC, respectively. When compared to the
      level in vehicle-treated control skin, these elevations were statistically
      significant. In irreversible papillomas harvested 20 weeks after the last TPA
      treatment, the levels of HETEs and etheno-DNA adducts were found to be slightly
      reduced, as compared to those in reversible papillomas, but were still increased
      over control levels in age-matched mice. Comparison of mean group values by
      simple regression analysis showed a close positive correlation between HETE and
      etheno-DNA adduct levels. Consistent with the miscoding properties of epsilondA
      causing mainly A --> T transversions, its increased formation in papillomas could
      thus contribute to this type of mutation in codon 61 of cHa-ras, shown to be a
      hallmark of DMBA-initiated and TPA-promoted mouse skin carcinogenesis. Although
      direct evidence that etheno adducts are derived from lipoxygenase-catalyzed
      metabolites of arachidonic acid is missing, our results implicate DNA damage by
      oxidative stress and lipid peroxidation as a cause of genetic instability
      observed at late stages of tumor promotion in mouse skin carcinogenesis.

PMID- 10956058
TI  - Formation of quinonoid-derived protein adducts in the liver and brain of Sprague
      Dawley rats treated with 2,2',5, 5'-tetrachlorobiphenyl.
AB  - A possible role for metabolic activation of 2,2',5, 5'-tetrachlorobiphenyl (TCB)
      to quinonoid metabolites was investigated in vitro in rat liver microsomes and in
      vivo in male Sprague-Dawley rats. Incubation of TCB with phenobarbital-induced
      rat liver microsomes resulted in metabolism of TCB to 3-hydroxy-TCB (3-OH-TCB)
      and 3,4-dihydroxy-TCB (3,4-diOH-TCB), which were further oxidized to form a
      reactive intermediate that bound to liver proteins. The predominant species
      observed in the Raney nickel assay for cysteinyl adducts was identified as 3,4
      diOH-TCB, consistent with an adduct having the structure 5-cysteinyl-3,6-dichloro
      4-(2', 5'-dichlorophenyl)-1,2-benzoquinone. This adduct may arise via the Michael
      addition of the sulfhydryl group of cysteine to 3, 6-dichloro-4-(2',5'
      dichlorophenyl)-1,2-benzoquinone (Cl(4)PhBQ). Metabolism of 3-OH-TCB by
      phenobarbital-induced microsomes in the presence of either NADPH or cumene
      hydroperoxide as a cofactor resulted in the formation of adducts. Dose-dependent
      formation of cysteinyl adducts was observed in liver cytosolic protein from rats
      treated with a single dose of TCB (0-200 mg/kg) by gavage. By regression
      analysis, the TCB adducts decayed with a half-life of 2. 03 +/- 0.131 days (mean
      +/- SE), which is approximately 2.5-fold shorter than the endogenous half-life
      for liver cytosolic protein in rat liver, suggesting adduct instability.
      Saturable formation of TCB adducts was observed in liver cytosolic protein of
      rats receiving multiple doses of TCB over 5 days. The levels of Cl(4)PhBQ-derived
      adducts were 2.1-fold greater than the estimated steady-state levels predicted by
      the single-dose treatment [97.7 +/- 13.2 vs 45.7 +/- 3. 73 (pmol/g)/(mg/kg of
      body weight)], suggesting induction of metabolism. A single cysteinyl adduct,
      inferred to be 5-cysteinyl-3, 6-dichloro-4-(2',5'-dichlorophenyl)-1,2
      benzoquinone, was detected in brain cytosolic protein of rats treated with
      multiple doses of TCB with levels of 15.2 (pmol/g)/(mg/kg of body weight).
      Implied involvement of a reactive quinone in the liver and brain of TCB-treated
      rats supports the idea that quinonoid metabolites may be important contributors
      to PCB-derived oxidative damage to genomic DNA.

PMID- 10956059
TI  - In vitro adduct formation of phosgene with albumin and hemoglobin in human blood.
AB  - The development of procedures for retrospective detection and quantitation of
      exposure to phosgene, based on adducts to hemoglobin and albumin, is described.
      Upon incubation of human blood with [(14)C]phosgene (0-750 microM), a significant
      part of radioactivity (0-13%) became associated with globin and albumin. Upon
      Pronase digestion of globin, one of the adducts was identified as the
      pentapeptide O=C-(V-L)-S-P-A, representing amino acid residues 1-5 of alpha
      globin, with a hydantoin function between N-terminal valine and leucine. Micro
      LC/tandem MS analyses of tryptic as well as V8 protease digests identified one of
      the adducts to albumin as a urea resulting from intramolecular bridging of lysine
      residues 195 and 199. The adducted tryptic fragment could be sensitively analyzed
      by means of micro-LC/tandem MS with multiple-reaction monitoring (MRM), enabling
      the detection in human blood of an in vitro exposure level of >/=1 microM
      phosgene.

PMID- 10956061
TI  - Reactivity of peroxynitrite versus simultaneous generation of (*)NO and O(2)(*)(
      ) toward NADH.
AB  - The oxidation of NADH by peroxynitrite takes place indirectly via the radical
      intermediates formed during the self-decomposition of peroxynitrite, i.e., (*)OH
      and (*)NO(2), and the oxidation yield exceeds 29% at relatively high NADH
      concentrations. The efficiency of oxidation of NADH by peroxynitrite is hardly
      affected by the presence of bicarbonate at physiological pH, and is remarkably
      increased when authentic peroxynitrite is replaced by low and equal fluxes of
      (*)NO and O(2)(*)(-). We determined the rate constants for the reactions of NADH
      with (*)OH, CO(3)(*)(-), and (*)NO(2) to be (2. 0 +/- 0.2) x 10(10), (1.4 +/-
      0.3) x 10(9), and (4.0 +/- 2.0) x 10(3) M(-)(1) s(-)(1), respectively. We show
      that the reaction of NADH with (*)OH in aerated solution does not form O(2)(*)(
      ), whereas the other one-electron oxidants oxidize NADH to NAD(*), which in turn
      very efficiently reduces oxygen to O(2)(*)(-). These results suggest that at
      physiological pH the oxidation of NADH by peroxynitrite in the absence or
      presence of bicarbonate occurs mainly through the reactions of NADH with (*)OH or
      CO(3)(*)(-), which are formed in about equal yields. The oxidation of NADH by
      continuous generation of (*)NO and O(2)(*)(-) proceeds via a chain mechanism, and
      therefore, the oxidation yield increases upon decreasing the flux of the
      radicals, and is higher than that obtained with authentic peroxynitrite.

PMID- 10956060
TI  - Sex dependence of the components and structure of urinary calculi induced by
      biphenyl administration in rats.
AB  - To obtain definitive information about the mechanisms of urinary calculus
      formation and the structural characteristics of the calculi induced by biphenyl
      administration in rats, with a focus on the sex dependency, the constituents of
      the urinary calculi were analyzed by HPLC, inductively coupled plasma
      spectroscopy (ICP), micro Fourier transform infrared spectroscopy (mFT-IR), and
      ion chromatography (IC), and structural analyses were carried out by microscopy,
      mFT-IR, and the electron probe microanalyzer (EPMA) method. We attempted to
      account for the appreciably higher incidence of calculi in males than in females.
      mFT-IR analysis revealed that the biphenyl-induced urinary calculi in male rats
      are composed mainly of potassium 4-hydroxybiphenyl-o-sulfate (4-HBPOSK), whereas
      the calculi in female rats are composed mainly of 4-hydroxybiphenyl (4-HBP) and
      KHSO(4) produced by the hydrolysis of 4-HBPOSK. Observations of photomicrographs
      and the results of mFT-IR analysis indicated that the calculi in males have a
      multilayer structure consisting of alternating layers of 4-HBPOSK and calcium
      phosphate, whereas the calculi in females have no multilayer structure, but open
      holes in which needle-shaped crystals are present in some places. In view of the
      results of these analyses, including the EPMA analysis, it appears that calculus
      formation in males may involve a series of successive and irreversible reactions,
      whereas calculus formation in females may result from a series of reversible
      reactions, including the hydrolysis of 4-HBPOSK. It was inferred that the series
      of irreversible reactions involved in calculus formation in males is relatively
      more stable than that in the case of females, and thus, a sex difference in the
      reaction features may be responsible for the observed difference in the incidence
      of calculus formation.

PMID- 10956062
TI  - Permeability, cytotoxicity, and genotoxicity of Cr(III) complexes and some Cr(V)
      analogues in V79 Chinese hamster lung cells.
AB  - The permeabilities and genotoxicities of the Cr(III) complexes [Cr(en)(3)](3+),
      mer-[Cr(glygly)(2)](-), cis-[Cr(phen)(2)(OH(2))(2)](3+), and trans
      [Cr(salen)(OH(2))(2)](+) and the Cr(V) analogues of cis
      [Cr(phen)(2)(OH(2))(2)](3+) and trans-[Cr(salen)(OH(2))(2)](+) [en being 1,2
      ethanediamine, glygly being glycylglycine, phen being 1,10-phenanthroline, and
      salen being N,N'-ethylenebis(salicylideneiminato)] have been studied in V79
      Chinese hamster lung cells. Following exposure of approximately 10(6) cells to
      0.4 mM Cr(III) for 4 h, the Cr uptake by single cells was less than 10(-)(14)
      g/cell (as determined by GFAAS analysis and as confirmed by PIXE analysis where
      the Cr concentration was below the limit of detection). Importantly, the Cr(V)
      analogue of cis-[Cr(phen)(2)(OH(2))(2)] was significantly more permeable than the
      Cr(III) complex. The cytotoxicity of the Cr(III) complexes increased in the
      following order: mer-[Cr(glygly)(2)](-) < [Cr(en)(3)](3+) approximately cis
      [Cr(phen)(2)(OH(2))(2)](3+) < trans-[Cr(salen)(OH(2))(2)](+). No genotoxic
      effects were observed following exposure to mer-[Cr(glygly)(2)](-) or
      [Cr(en)(3)](3+) at concentrations up to 6 mM. The Cr(III) imine complexes trans
      [Cr(salen)(OH(2))(2)](+) and cis-[Cr(phen)(2)(OH(2))(2)](3+), which could be
      oxidized to Cr(V) complexes, induced MN in vitro at rates of 13.6 and 3.3 MN/1000
      BN cells/micromol of Cr, respectively. The comparative permeabilities and
      genotoxicities of trans-[Cr(salen)(OH(2))(2)](+) and [CrO(salen)](+) were similar
      due to the instability of the Cr(V) complex at physiological pH values (7.4).
      There was a substantial increase in the permeability of [Cr(O)(2)(phen)(2)](+),
      compared to that of the Cr(III) analogue, which was accompanied by a highly
      genotoxic response. Consequently, any Cr(III) complex that is absorbed by cells
      and can be oxidized to Cr(V) must be considered as a potential carcinogen. This
      has potential implications for the increased use of Cr(III) complexes as dietary
      supplements and highlights the need to consider the genotoxicities of a variety
      of Cr(III) complexes when determining the carcinogenic potential of Cr(III)
      particularly when "high" deliberately administered doses are concerned.

PMID- 10956063
TI  - Oxidative metabolites of 5-S-cysteinylnorepinephrine are irreversible inhibitors
      of mitochondrial complex I and the alpha-ketoglutarate dehydrogenase and pyruvate
      dehydrogenase complexes: possible implications for neurodegenerative brain
      disorders.
AB  - The major initial product of the oxidation of norepinephrine (NE) in the presence
      of L-cysteine is 5-S-cysteinylnorepinephrine which is then further easily
      oxidized to the dihydrobenzothiazine (DHBT) 7-(1-hydroxy-2-aminoethyl)-3,4
      dihydro-5-hydroxy-2H-1, 4-benzothiazine-3-carboxylic acid (DHBT-NE-1). When
      incubated with intact rat brain mitochondria, DHBT-NE-1 evokes rapid inhibition
      of complex I respiration without affecting complex II respiration. DHBT-NE-1 also
      evokes time- and concentration-dependent irreversible inhibition of NADH-coenzyme
      Q(1) (CoQ(1)) reductase, the pyruvate dehydrogenase complex (PDHC), and alpha
      ketoglutarate dehydrogenase (alpha-KGDH) when incubated with frozen and thawed
      rat brain mitochondria (mitochondrial membranes). The time dependence of the
      inhibition of NADH-CoQ(1) reductase, PDHC, and alpha-KGDH by DHBT-NE-1 appears to
      be related to its oxidation, catalyzed by an unknown component of the inner
      mitochondrial membrane, to electrophilic intermediates which bind covalently to
      active site cysteinyl residues of these enzyme complexes. The latter conclusion
      is based on the ability of glutathione to block inhibition of NADH-CoQ(1)
      reductase, PDHC, and alpha-KGDH by scavenging electrophilic intermediates,
      generated by the mitochondrial membrane-catalyzed oxidation of DHBT-NE-1, forming
      glutathionyl conjugates, several of which have been isolated and
      spectroscopically identified. The possible implications of these results to the
      degeneration of neuromelanin-pigmented noradrenergic neurons in the locus
      ceruleus in Parkinson's disease are discussed.

PMID- 10956064
TI  - Identification of tamoxifen-DNA adducts induced by alpha-acetoxy-N
      desmethyltamoxifen.
AB  - Treatment with tamoxifen increased the risk of endometrial cancers in breast
      cancer patients and women participating in the chemoprevention study. In our
      laboratory, tamoxifen-DNA adducts, including alpha-(N(2)
      deoxyguanosinyl)tamoxifen (dG-N(2)-TAM), were detected in the endometrium of
      women taking tamoxifen [Shibutani, S., et al. (1999) Chem. Res. Toxicol. 12, 646
      653]. On the basis of recent animal studies, deoxyguanosinyl-N-desmethyltamoxifen
      (dG-N-desmethylTAM) adducts are also suspected to be formed in the liver. In the
      study presented here, we synthesized alpha-acetoxy-N-desmethyltamoxifen as a
      model activated metabolite of N-desmethyltamoxifen. The overall yield of alpha
      acetoxy-N-desmethyltamoxifen from alpha-hydroxytamoxifen was approximately 42%.
      alpha-Acetoxy-N-desmethyltamoxifen was highly reactive to 2'-deoxyguanosine, as
      was similarly observed for tamoxifen alpha-sulfate. The two reaction products
      were identified as a mixture of epimers of the trans form or cis form of alpha
      (N(2)-deoxyguanosinyl)-N-desmethyltamoxifen (dG-N(2)-N-desmethylTAM) by mass and
      proton magnetic resonance spectroscopy. In addition, the trans and cis forms of
      dG 3'-monophosphate-N(2)-N-desmethylTAM were prepared as standard markers for
      (32)P-postlabeling/HPLC analysis. Using this technique, dG-N(2)-N-desmethylTAM
      adducts were detected in calf thymus DNA reacted with alpha-acetoxy-N
      desmethyltamoxifen.

PMID- 10956065
TI  - Structure determination of carboxyhomoyessotoxin, a new yessotoxin analogue
      isolated from adriatic mussels.
AB  - The contamination of shellfish with marine biotoxins derived from microalgae
      represents a serious problem for shellfish industries and public health. This
      study investigated the composition of diarrhetic shellfish toxins in the
      digestive glands of mussels from the Northern Adriatic Sea. Along with known
      yessotoxins, identified by comparison of their chromatographic and spectral
      properties with those reported in the literature, we isolated a new analogue of
      yessotoxin, carboxyhomoyessotoxin, whose structure was determined by mass
      spectrometry and (1)H NMR spectroscopy.

PMID- 10956066
TI  - Characterization of novel glutathione adducts of a non-nucleoside reverse
      transcriptase inhibitor, (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)
      3, 4-dihydro-2(1H)-quinazolinone (DPC 961), in rats. Possible formation of an
      oxirene metabolic intermediate from a disubstituted alkyne.
AB  - The postulated formation of oxirene-derived metabolites from rats treated with a
      disubstituted alkyne, (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-3,
      4-dihydro-2(1H)-quinazolinone (DPC 961), is described. The reactivity of this
      postulated oxirene intermediate led to the formation of novel glutathione adducts
      whose structures were confirmed by LC/MS and by two-dimensional NMR experiments.
      These metabolites were either excreted in rat bile or degraded to mercapturic
      acid conjugates and eliminated in urine. To demonstrate the oxidation of the
      triple bond, an analogue of DPC 961 was synthesized, whereby the two carbons of
      the alkyne moiety were replaced with (13)C stable isotope labels. Rats were
      orally administered [(13)C]DPC 961 and glutathione adducts isolated from bile.
      The presence of an oxygen atom on one of the (13)C labels of the alkyne was
      demonstrated unequivocally by NMR experiments. Administration of (14)C-labeled
      DPC 961 showed that biliary elimination was the major route of excretion with the
      8-OH glucuronide conjugate (M1) accounting for greater than 90% of the eliminated
      radioactivity. On the basis of radiochemical profiling, the glutathione-derived
      metabolites were minor in comparison to the glucuronide conjugate. Studies with
      cDNA-expressed rat enzymes, polyclonal antibodies, and chemical inhibitors
      pointed to the involvement of P450 3A1 and P450 1A2 in the formation of the
      postulated oxirene intermediate. The proposed mechanism shown in Scheme 1 begins
      with P450-catalyzed formation of an oxirene, rearrangement to a reactive
      cyclobutenyl ketone, and a 1,4-Michael addition with endogenous glutathione to
      produce two isomeric adducts, GS-1 and GS-2. The glutathione adducts were
      subsequently catabolized via the mercapturic acid pathway to cysteinylglycine,
      cysteine, and N-acetylcysteine adducts. The transient existence of the alpha,beta
      unsaturated cyclobutenyl ketone was demonstrated by incubating the glutathione
      adduct in the presence of N-acetylcysteine and monitoring the formation of N
      acetylcysteine adducts by LC/MS. Epimerization of GS-1 to GS-2 was also observed
      when N-acetylcysteine was omitted from the incubation.

PMID- 10956067
TI  - N-Acetylbenzidine-DNA adduct formation by phorbol 12-myristate-stimulated human
      polymorphonuclear neutrophils.
AB  - N'-(3'-Monophosphodeoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is the major
      adduct in exfoliated urothelial cells and in peripheral white blood cells of
      workers exposed to benzidine. This study was designed to assess the metabolic
      pathways leading to dGp-ABZ formation in human peripheral white blood cells.
      [(3)H]-N-Acetylbenzidine (ABZ) transformation was assessed using myeloperoxidase
      (MPO), hypochlorous acid (HOCl), and human peripheral white blood cells in the
      absence and presence of DNA or dGp. MPO metabolism required H(2)O(2), but not
      NaCl. While transformation by HOCl was completely inhibited by 10 mM taurine, the
      level of metabolism of ABZ by MPO was only reduced 56%. Transformation by either
      MPO or HOCl was inhibited by 100 mM DMPO, 1 mM glutathione, and 1 mM ascorbic
      acid. Glutathione formed a new product with MPO, but not with HOCl. Previously
      identified oxidation products of ABZ, N'-hydroxy-N-acetylbenzidine or 4'-nitro-4
      acetylaminobiphenyl, were not detected. With DNA or dGp present, a new product
      was observed that corresponded to synthetic dGp-ABZ in its HPLC elution profile,
      in nuclease P(1) hydrolysis to dG-ABZ, and in (32)P-postlabeling analysis. The
      HOCl-derived adduct was identified by electrospray ionization mass spectrometry,
      with collision-activated dissociation, as dGp-ABZ. Metabolism of [(3)H]ABZ by
      peripheral blood cells was stimulated about 3-fold with 30 ng/mL beta-phorbol 12
      myristate 13-acetate (PMA). Using (32)P-postlabeling, dGp-ABZ was detected only
      in the presence of PMA and its level was increased more than 300-fold if either
      0.7 mg/mL DNA or dGp was present. Indomethacin (0.1 mM) did not alter adduct
      formation. With dGp, dGp-ABZ formation could be detected with as little as 0.12 x
      10(6) neutrophils. Using specific chromatographic and enzymatic techniques,
      neutrophil-derived dGp-ABZ was identical to the synthetic standard. Thus, these
      results are consistent with human polymorphonuclear neutrophils forming dGp-ABZ
      by a peroxidatic mechanism involving MPO.

PMID- 10956068
TI  - Reductions of nitro and 9-Oxo groups of environmental nitrofluorenes by the rat
      mammary gland in vitro.
AB  - Nitrofluorenes and C-9-oxidized nitrofluorenes are widespread environmental
      genotoxins which may be relevant for breast cancer on the basis of their
      carcinogenicities, particularly of 2, 7-dinitrofluorene (2,7-diNF), for the rat
      mammary gland. Since their metabolism to active carcinogens may involve
      nitroreduction, this study examined the reduction of 2-nitrofluorene (2-NF) and
      2,7-diNF and their 9-oxo- and 9-hydroxy (OH) derivatives by the rat mammary
      gland. Cytosolic fractions catalyze NADH- and NADPH-dependent reductions of the 2
      nitro and 9-oxo to the respective 2-amino and 9-OH compounds at rates 4- and
      >/=10-fold greater than those with microsomes. Rates of amine formation catalyzed
      by cytosol from 2, 7-diNF are greater than the rate from 2-NF and increase for C
      9-oxidized derivatives: 9-oxo-2-NF > 9-OH-2-NF > 2-NF and 9-OH-2, 7-diNF >> 9-oxo
      2,7-diNF > 2,7-diNF. Nitroreduction is inhibited by O(2) or allopurinol (20
      microM), dicoumarol (100 microM), and rutin (50 microM). 9-Oxoreduction is
      inhibited by rutin, dicoumarol, and indomethacin (100 microM), but not by O(2) or
      allopurinol. Pyrazole or menadione does not inhibit nitro or 9-oxoreduction.
      Xanthine, hypoxanthine, 2-hydroxypyrimidine, and N'-methylnicotinamide support
      cytosol-catalyzed nitro, but not 9-oxo, reduction. The data suggest that the
      nitroreduction is catalyzed largely by a xanthine oxidase and partially by a
      diaphorase and 9-oxoreduction by a carbonyl reductase. The extents of the nitro
      and carbonyl reductions of the nitrofluorenes may determine their reactivities
      with DNA, and thus genotoxicities for the mammary gland.

PMID- 10956069
TI  - Purification of ethoxyquin and its two oxidation products.
AB  - 2,6-Dihydro-2,2,4-trimethyl-6-quinolone (QI) and 1,8'-bis(1, 2-dihydro-6-ethoxy
      2,2,4-trimethylquinoline) (DM) are two oxidation products of 1,2-dihydro-6-ethoxy
      2,2,4-trimethylquinoline (ethoxyquin, EQ). This paper describes several methods
      for the purification of technical grade EQ and for the production of pure QI and
      DM as standards with the purity required (>99%) for calibration of quantitative
      determination methods. EQ of high purity was obtained through vacuum distillation
      followed by a quick column chromatographic purification on silica gel.
      Preparative scale purity DM could be obtained through recrystallization from
      methanol, but QI could be purified only by a high-pressure liquid chromatographic
      method.

PMID- 10956070
TI  - Oxidative stability of conjugated linoleic acid isomers.
AB  - Conjugated linoleic acids (CLAs) have been shown to be a strong anticarcinogen in
      a number of animal models. Our previous study demonstrated that CLA as a whole
      was extremely unstable in air. The present study was undertaken further to
      examine the oxidative stability of individual CLA isomers using the combination
      of gas-liquid chromatography (GLC) and silver ion high-performance liquid
      chromatography (Ag-HPLC). It was found that CLA as a whole oxidized rapidly and
      more than 80% was degraded within 110 h in air at 50 degrees C. Four c,c-CLA
      isomers were most unstable followed by four c,t-CLA isomers. In contrast, four
      t,t-CLA isomers were relatively stable under the same experimental conditions.
      Both the oxygen consumption and the GLC analysis revealed that 200 ppm jasmine
      green tea catechins (GTCs) exhibited protection to CLA and were even stronger
      than 200 ppm butylated hydroxytoluene (BHT) when added to either CLA or canola
      oil containing 10% CLA. The present study emphasized that oxidative unstability
      of CLA should not be overlooked although CLA has many biological effects.

PMID- 10956071
TI  - Ability of surfactant hydrophobic tail group size to alter lipid oxidation in oil
      in-water emulsions.
AB  - Oxidation of oil-in-water emulsion droplets is influenced by the properties of
      the interfacial membrane surrounding the lipid core. Previous work has shown that
      an important factor in the oxidation of oil-in-water emulsions is surfactant
      properties that impact interactions between water-soluble prooxidants and lipids
      in the emulsion droplet. The purpose of this research was to study the impact of
      surfactant hydrophobic tail group size on lipid oxidation in oil-in-water
      emulsions stabilized by polyoxyethylene 10 lauryl ether (Brij-lauryl) or
      polyoxyethylene 10 stearyl ether (Brij-stearyl). The ability of iron to decompose
      cumene peroxide was similar in hexadecane emulsions stabilized by Brij-stearyl
      and Brij-lauryl. Oxidation of methyl linoleate in hexadecane emulsions containing
      cumene peroxide was greater in droplets stabilized by Brij-lauryl than in those
      stabilized by Brij-stearyl at pH 3 with no differences observed at pH 7.0.
      Oxidation of salmon oil was greater in emulsions stabilized by Brij-lauryl than
      in those stabilized by Brij-stearyl as determined by both lipid peroxides and
      headspace propanal. These results suggest that surfactant hydrophobic tail group
      size may play a minor role in lipid oxidation in oil-in-water emulsions.

PMID- 10956072
TI  - Amino acid profiles after sprouting, autoclaving, and lactic acid fermentation of
      finger millet (Eleusine coracan) and kidney beans (Phaseolus vulgaris L.).
AB  - Seeds of finger millet (Eleucine coracan (L.) Gaertner) and kidney beans
      (Phaseolus vulgaris L.) were sprouted, autoclaved, and fermented during the
      processing of a weaning (complementary) food for children. Relative changes in
      individual amino acids with processing were evaluated. Finger millet and kidney
      beans both showed a good percentage of essential to total amino acids, with 44. 2
      44.9% in finger millet and 44.2-45.1% in kidney beans, when compared to 33.9% for
      the FAO/WHO reference protein for 2-5 year old children. Sprouting resulted in a
      significant decrease in lysine in kidney beans. Autoclaving caused significant
      decreases in histidine, while fermentation significantly decreased phenylalanine
      and increased tryptophan in finger millet. The leucine-to-lysine ratio, which is
      an indicator of the pellagragenic character of a protein, was significantly
      improved in finger millet by both sprouting and fermentation.

PMID- 10956073
TI  - Steady-state kinetics and thermodynamics of the hydrolysis of beta-lactoglobulin
      by trypsin.
AB  - Hydrolysis of beta-lactoglobulin (in an equimolar mixture of the A and B variant)
      by trypsin in neutral aqueous solution [pH 7.7 at 25 degrees C, ionic strength
      0.08 (NaCl)] was followed by capillary electrophoresis and thermodynamic
      parameters derived from a Michaelis-Menten analysis of rate data obtained at 10,
      20, 30, and 40 degrees C for disappearance of beta-lactoglobulin. Enthalpy of
      substrate binding to the enzyme and the energy of activation for the catalytic
      process were found to have the values, DeltaH(bind) = -28 +/- 4 kJ mol(-)(1) and
      E(a) = 51 +/- 18 kJ mol(-)(1), respectively. Thus, beta-lactoglobulin shows an
      enthalpy of activation for free substrate reacting with free enzyme of about 21
      kJ mol(-)(1), corresponding to a transition state stabilization of 60 kJ mol(
      )(1) when compared to acid-catalyzed hydrolysis. The catalytic efficiency of
      trypsin in hydrolysis of beta-lactoglobulin is increased significantly by
      temperature; however, this effect is partly counteracted by a weaker substrate
      binding resulting in an increase by only 25%/10 degrees C in overall catalytic
      efficiency.

PMID- 10956075
TI  - Decay of methidathion on Greek soultanina grapes during storage and on the vines.
AB  - Decomposition of the pesticide methidathion on and in soultanina (Thomson
      seedless) grapes was studied. Vines, uncovered and covered were sprayed with the
      pesticide. Samples were collected and analyzed in regular time intervals. Two
      lots were collected, the first of them, 2 h after spraying and the second 20 days
      later, and were stored in a commercial refrigerated room. Degradation of the
      pesticide was studied for about 50 days for the grapes on the vines and 130 days
      for the grapes stored in the refrigerated room. The half-life of the pesticide
      methidathion was found to be 5 days for the uncovered vines, 7 days for the
      covered vines and 64 days for the grapes stored in the refrigerator.

PMID- 10956074
TI  - Light-induced oxidative changes in a model dairy spread. Wavelength dependence of
      quantum yields.
AB  - Light-induced formation of lipid peroxides in a water-in-oil emulsion based on
      purified rape-seed oil (80%) was found to increase with decreasing wavelength and
      to have the (apparent) quantum yields (1.1 +/- 0.1) x 10(-)(3) for 436 nm, (2.6
      +/- 0.1) x 10(-)(3) for 405 nm, and (4.5 +/- 0.4) x 10(-)(3) for 366 nm
      irradiation, as determined after 12 h of exposure to monochromatic light of an
      approximate intensity of 10(18) quanta.min(-)(1).mL(-)(1) and related to total
      light absorption. Riboflavin (0.8 ppm) had no effect on lipid peroxidation, but
      photodegraded with a quantum yield ((1.5 +/- 0.3) x 10(-)(5) for 436 nm, (1.7 +/-
      0.2) x 10(-)(5) for 405 nm and (1.39 +/- 0.09) x 10(-)(5) for 366 nm irradiation)
      independent of irradiation wavelength. beta-Carotene was only photodegraded to a
      minor extent, but protected riboflavin against photodegradation and the lipids
      against peroxidation for 436 and 405 nm irradiation (reduction in quantum yield
      three times for 4.5 ppm beta-carotene for lipid oxidation and more for riboflavin
      degradation), but not for 366 nm irradiation, where beta-carotene has an
      absorption minimum.

PMID- 10956076
TI  - Saccharomyces cerevisiae mannoproteins that protect wine from protein haze: their
      release during fermentation and lees contact and a proposal for their mechanism
      of action.
AB  - A fraction containing the mannoproteins released during fermentation from the
      winemaking strain of Saccharomyces cerevisiae, Maurivin PDM, was able to reduce
      the visible protein haze in white wine. This fraction of haze protective
      mannoprotein material (HPM) could be recovered by either ultrafiltration or
      ethanol precipitation. The kinetics of the release of both mannose- and glucose
      containing polymers during the growth cycle of PDM were determined as a guide to
      the release of HPM. Active HPM was first detected in the culture supernatant when
      the cells were exponentially growing. HPM was also released into the medium under
      an environment simulating winemaking conditions by PDM cells during fermentation
      as well as during storage on yeast lees. Since the amounts of HPM released during
      fermentation are greater than those subsequently extracted from the cell wall,
      fermentation would be a more viable procedure than extraction from yeast cells
      for the commercial production of HPM. Yeast invertase, a mannoprotein with haze
      protective activity, was used as a model substrate to investigate the mechanism
      of haze protection. Invertase was found to reduce visible turbidity but not
      prevent protein precipitation. Invertase itself did not precipitate but remained
      soluble in the wine. On the basis of these observations, we propose that the
      mechanism of haze protection may be one of competition between HPM and wine
      proteins for unknown wine component(s), the latter being required for the
      formation of large insoluble aggregates of denatured protein. As the available
      concentration of these components decreases, due to the presence of HPM, the
      particle size of the haze decreases and thus visible turbidity declines.

PMID- 10956077
TI  - Potential antioxidants in beer assessed by ESR spin trapping.
AB  - A number of potential antioxidants have been evaluated for their effect on
      formation of radicals in beer using the electron spin resonance (ESR) lag phase
      method. Sulfite was found to be the only compound that was able to delay the
      formation of radicals, whereas phenolic compounds such as phenolic acids,
      catechin, epicatechin, and proanthocyanidin dimers had no effect on the formation
      of radicals. Ascorbate, cystein, and cysteamin were on the other hand found to be
      prooxidants. It is suggested that antioxidants must be able to either scavenge
      peroxides or trap metal ions in order to be effective in beer. The effectiveness
      of sulfite is suggested to be a consequence of its two-electron nonradical
      producing reaction with peroxides.

PMID- 10956078
TI  - Rheological and physical properties of derivitized whey protein isolate powders.
AB  - Pregelatinized starch is employed in many food applications due to the
      instantaneous nature of thickening and stability imparted by modification.
      Proteins, however, have been excluded as a viscosifying agent due to requisite
      thermal treatments required to create structure. Whey protein isolate gels were
      produced while manipulating heating time, pH, and mineral type/content, producing
      a variety of gel types/networks. Gels were frozen, freeze-dried, and ground into
      a powder. Once reconstituted in deionized water, gel powders were evaluated based
      on solubility studies, rotational viscometry, and electrophoresis. The protein
      powder exhibiting the largest apparent viscosity, highest degree of hydrolysis,
      and greatest solubility was selected for pH and temperature stability analyses
      and small amplitude oscillatory rheology. This processing technique manipulates
      WPI into a product capable of forming cold-set weak gel structures suitable for
      thickening over a wide range of temperature and pH food systems.

PMID- 10956079
TI  - Simple method of isolation and purification of alpha-galactosides from legumes.
AB  - A simple method for the isolation and purification of alpha-galactosides,
      raffinose family oligosaccharides (RFOs), from legumes has been developed. The
      method includes (i) imbibition of seeds, (ii) extraction with 50% ethanol, (iii)
      precipitation of RFOs, (iv) purification of RFOs on diatomaceous earth and
      charcoal, and (v) cation-exchange chromatography. The described method allows one
      to obtain high purity RFO preparations (90% for lentil and 80% for pea seeds,
      determined by HPLC-RI analysis) in the form of white, fine powder. Yields of
      alpha-galactosides isolated from 100 g of seeds of lentil and pea were 5.6 and
      4.3 g, respectively.

PMID- 10956080
TI  - Release of allergenic proteins from rice grains induced by high hydrostatic
      pressure.
AB  - Protein release from rice grains during high-pressure treatment was investigated.
      When polished rice grains were immersed in distilled water and pressurized at 100
      400 MPa, a considerable amount of proteins (0.2-0.5 mg per gram of grains) was
      released. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      immunoblot analyses, the major proteins released were identified as 16 kDa
      albumin, alpha-globulin, and 33 kDa globulin, which were known as major rice
      allergens. By scanning electron microscopic observation of rice grains
      pressurized at 300 MPa, partial morphological changes in endosperm cells but no
      apparent structural changes in protein bodies were detected. The content of these
      allergenic proteins decreased by pressurization and almost completely disappeared
      from rice grains by the pressurization in the presence of proteolytic enzyme.
      These results suggest that partial destruction of endosperm cells caused by
      pressurization enhances permeability of a surrounding solution into rice grains
      and that a part of the proteins are solubilized and subsequently released into a
      surrounding solution.

PMID- 10956082
TI  - Effect of pH on lipid oxidation using trout hemolysate as a catalyst: a possible
      role for deoxyhemoglobin.
AB  - Hemoglobin-mediated lipid oxidation was studied by adding hemolysate to washed
      cod muscle. Three pH values were examined (pH 7.6, 7.2, and 6.0). The lag time
      prior to rancidity and thiobarbituric acid reactive substance development
      decreased greatly as the pH was reduced (p < 0.01). Formation of methemoglobin
      due to autoxidation of the heme pigment was found to occur more rapidly at
      reduced pH. Also, the level of deoxyhemoglobin was found to sharply increase with
      pH reduction in the range of pH 7.6-6.0. This suggested a potential role for
      deoxyhemoglobin as a catalyst. ATP lowered hemoglobin oxygenation at pH 7.2.
      Peroxidation of linoleic acid by oxy/deoxyhemoglobin and methemoglobin was
      investigated at two levels of preformed lipid hydroperoxides. At a reduced level
      of preformed lipid hydroperoxides, oxy/deoxyhemoglobin stimulated peroxidation of
      linoleic acid, whereas methemoglobin did not. At the higher level of preformed
      lipid hydroperoxides, both oxy/deoxyhemoglobin and methemoglobin were active.
      This investigation suggests that reduced hemoglobins played an important role in
      lipid oxidation processes.

PMID- 10956081
TI  - Isolation and identification of novel tocotrienols from rice bran with
      hypocholesterolemic, antioxidant, and antitumor properties.
AB  - Two novel tocotrienols were isolated from stabilized and heated rice bran, apart
      from the known alpha-, beta-, gamma-, and delta-tocopherols and tocotrienols.
      These new tocotrienols were separated by HPLC, using a normal phase silica
      column. Their structures were determined by ultraviolet, infrared, nuclear
      magnetic resonance, circular dichroism, and high-resolution mass spectroscopies
      and established as desmethyl tocotrienol [3, 4-dihydro-2-methyl-2-(4,8,12
      trimethyltrideca-3'(E),7'(E), 11'-trienyl)-2H-1-benzopyran-6-ol] and didesmethy
      tocotrienol [3, 4-dihydro-2-(4,8,12-trimethyltrideca-3'(E),7'(E), 11'-trienyl)-2H
      1-benzopyran-6-ol]. These tocotrienols significantly lowered serum total and LDL
      cholesterol levels and inhibited HMG-CoA reductase activity in chickens. They had
      much greater in vitro antioxidant activities and greater suppression of B16
      melanoma cell proliferation than alpha-tocopherol and known tocotrienols. Results
      indicated that the number and position of methyl substituents in tocotrienols
      affect their hypocholesterolemic, antioxidant, and antitumor properties.

PMID- 10956083
TI  - Fractionation and characterization of mushroom dietary fiber (nonstarch
      polysaccharides) as potential nutraceuticals from sclerotia of Pleurotus tuber
      regium (Fries) singer.
AB  - The nonstarch polysaccharides (NSPs) in the total dietary fiber (TDF) from the
      sclerotia of Pleurotus tuber-regium (tiger milk mushroom) were fractionated by
      the sequential use of chemical solvents. About half of the TDF was solubilized
      and two major alkali-soluble fractions (1 and 4 N sodium hydroxide) that
      contained 126 and 293 g/kg TDF were obtained. Sugar analysis and infrared
      spectroscopy indicated that the NSPs in these alkali-soluble fractions were
      mainly beta-glucans and chitin. These alkali-soluble NSPs were further purified
      by anion-exchange chromatography followed by gel permeation chromatographic
      separation. Methylation analysis revealed that these purified glucans were highly
      branched and contained a mixture of sugar linkages of beta-1,3, beta-1,6, and
      beta-1,4. The potential use of these sclerotial beta-glucans as nutraceuticals
      was discussed.

PMID- 10956084
TI  - Contribution of pyrrole formation and polymerization to the nonenzymatic browning
      produced by amino-carbonyl reactions.
AB  - Recent studies have hypothesized that pyrrole formation and polymerization may be
      contribute to the nonenzymatic browning produced in both oxidized lipid/protein
      reactions and the Maillard reaction. To develop a methodology that would allow
      investigation of the contribution of this browning mechanism, the kinetics of
      formation of color, fluorescence, and pyrrolization in 4, 5(E)-epoxy-2(E)
      heptenal/lysine and linolenic acid/lysine model systems were studied. In both
      cases similar kinetics for the three measurements were observed at the two
      temperatures assayed (37 and 60 degrees C), and there was a high correlation
      among color, fluorescence, and pyrrolization measurements obtained as a function
      of incubation time. Because the color and fluorescence production in the 4,5(E)
      epoxy-2(E)-heptenal/lysine system is a consequence of pyrrole formation and
      polymerization, the high correlations observed with the unsaturated fatty acid
      also suggest a contribution of the pyrrole formation and polymerization to the
      development of color and fluorescence observed in the fatty acid/lysine system.
      Although the contribution of other mechanisms cannot be discarded, all of these
      results suggest that when the pyrrole formation and polymerization mechanism
      contributes to the nonenzymatic browning of foods, a high correlation among
      color, fluorescence, and pyrrolization measurements should be expected.

PMID- 10956085
TI  - Relation between solubility and surface hydrophobicity as an indicator of
      modifications during preparation processes of commercial and laboratory-prepared
      soy protein isolates.
AB  - Because water solubility is the main hydration property of proteins, solubility
      values of commercial and laboratory soy protein isolates, prepared under
      different conditions, were comparatively analyzed. In contrast, the surface
      hydrophobicity manifested by proteins is a physicochemical property that
      determines, to a great extent, the tendency of protein molecules to aggregate and
      so to lose solubility. On these grounds, the solubility of isolates was analyzed
      as a function of the surface hydrophobicity of their proteins, and, as a result,
      three well-defined groups of laboratory isolates were identified: (A) native, (B)
      partially or totally denatured with high solubility and surface hydrophobicity,
      and (C) totally denatured with low solubility and surface hydrophobicity.
      Commercial isolates could not be included in any of these groups; they were
      grouped as (A') partially native and (C') totally denatured. Solubility values in
      these two groups were similar to those of group C, but the surface hydrophobicity
      levels were much lower. The different processes leading to the groups mentioned
      above are discussed, along with the way the soy proteins are influenced by the
      specific preparation conditions, namely, protein concentration, chemical or
      thermal treatments, presence of salts, drying, and phospholipid addition, among
      others.

PMID- 10956086
TI  - Identification of 4-O-5'-coupled diferulic acid from insoluble cereal fiber.
AB  - The extracts of saponified cereal fibers of whole grains of corn (Zea mays cv.
      microsperma KOERN.), wheat (Triticum aestivum L.), spelt (Triticum spelta L.),
      and rice (Oryza sativa L.) were investigated for dehydrodimers of ferulic acid
      using gas-liquid chromatography (GLC) with mass spectrometric detection (GLC-MS)
      and flame ionization detection (GLC-FID). In addition to the 8,5'-, 8, 8'-, 5,5'
      , and 8-O-4'-coupled diferulic acids previously identified from other plant
      materials the 4-O-5'-coupled diferulic acid (E)-3-[4-[(E)-2-carboxyvinyl]-2
      methoxyphenoxy]-4-hydroxy-5-methoxyci nnamic acid (4-O-5'-DFA) was identified in
      all fibers investigated. This new diferulate was authenticated by comparison of
      its mass spectrum and its relative GLC retention time with those of the
      synthesized compound. Semiquantitative determination of 4-O-5'-DFA showed that it
      is present at 8-30 microg/g, approximately 70-100 times lower concentrations than
      the sum of 8,5'-coupled diferulic acids, the major diferulic acids in the
      investigated fibers.

PMID- 10956087
TI  - Evaluation of antioxidant and prooxidant activities of bamboo Phyllostachys nigra
      var. Henonis leaf extract in vitro.
AB  - Solvent-extracted bamboo leaf extract (BLE) containing chlorogenic acid, caffeic
      acid, and luteolin 7-glucoside was evaluated in vitro for free radical scavenging
      and antioxidant activities using a battery of test methods. BLE exhibited a
      concentration-dependent scavenging activity of DPPH radical. BLE prolonged the
      lag phase and suppressed the rate of propagation of liposome peroxidation
      initiated by peroxyl radical induced by 2,2'-azobis(2-amidinopropane
      dihydrochloride (AAPH) at 37 degrees C. BLE also prevented human low-density
      lipoprotein oxidation, mediated by Cu(2+), which was monitored by the lower
      formation of conjugated diene and fluorescence and a reduced negative charge of
      apo-B protein. Finally, BLE protected supercoiled DNA strand against scission
      induced by AAPH-mediated peroxyl radical. Prooxidant activity of BLE was seen in
      a Cu(2+)-induced peroxidation of structured phosphatidylcholine liposome,
      indicating catalytic peroxidation due to a relatively high reducing power of BLE.
      It was concluded that the BLE has both antioxidant activity and prooxidant
      activity; the antioxidant activity was attributed to free radical scavenging
      activity, and the prooxidant activity, albeit minor, resulted from the reducing
      power of plant phenolics in the presence of transitional metal ions.

PMID- 10956088
TI  - Differentiation-inducing effects of small fruit juices on HL-60 leukemic cells.
AB  - Epidemiological studies indicate that high intakes of fruits and vegetables are
      associated with a reduced risk of cancer, and several plant-derived drugs have
      been developed in medical oncology. Since only a small part of the flora has been
      tested for any kind of bioactivity, we chose small fruits as sources of
      differentiation-inducing activity against HL-60 leukemic cells. We have prepared
      juices from various small fruits that grow mainly in the northern part of Japan.
      Screening of 43 samples indicated that juices of Actinidia polygama Maxim., Rosa
      rugosa Thunb., Vaccinium smallii A. Gray, and Sorbus sambucifolia Roem. strongly
      induced differentiation of HL-60 cells to monocyte/macrophage characteristics in
      a concentration-dependent manner as indicated by histochemical and biochemical
      examinations.

PMID- 10956090
TI  - Relationship between the activity of soybean lipoxygenase 1 and the
      physicochemical characteristics of model food emulsion systems.
AB  - The paper describes the relationship between the physicochemical characteristics
      of model oi-in-water emulsion systems containing oil droplets and soluble
      fragments (monomers and micelles) and the activity of pure soybean lipoxygenase
      1. The method of emulsification, as well as the chemistry and concentration of
      surfactant and substrate molecules, was manipulated to modify the overall
      physicochemical properties of ternary emulsions. The effect of these experimental
      factors on the size and relative concentration of oil droplets and soluble
      fragments was examined with static light scattering and turbidity measurements.
      Lipoxygenase 1 activity was assayed polarographically. Experimental factors that
      increase the critical micelle concentration of the monomers and facilitate their
      transport out of micelles, as well as across the oil-water interfaces and into
      the aqueous phase, were shown to improve the activity of the enzyme and vice
      versa.

PMID- 10956089
TI  - Hypotriglyceridemic effect of Anka (a fermented rice product of monascus sp.) in
      rats.
AB  - Experimental rats with hypertriglyceridemia were prepared by feeding a high
      fructose diet. Dried Anka powder (2%), a rice product fermented with Monascus
      sp., was mixed with basic high-fructose (30%) or basal-diet feed. Serum and liver
      lipids were measured after 6 months. The concentrations of serum triglycerides,
      total cholesterol, VLDL-C, and LDL-C had significantly decreased, whereas that of
      HDL-C had slightly increased in 30% fructose-Anka-fed rats as compared with the
      30% fructose-fed rats, but hepatic lipase activity had increased in the Anka-fed
      groups. The ratio of lipoprotein lipase/hepatic lipase was not significantly
      different between 30% fructose-Anka-fed rats and 30% fructose-fed rats. The
      dietary intake and weight of these two groups were approximately the same.
      Similar results were obtained in noninduced hypertriglyceridemic rats. The
      concentrations of triglycerides and cholesterol did not significantly differ in
      the liver. Interestingly, Anka can suppress serum triglycerides in rats with
      induced hypertriglyceridemia. The antioxidant enzyme SOD activity was also
      measured in serum, and no significant change was observed. On the basis of these
      findings, we suggest that Anka may be used to suppress hypertriglyceridemia and
      hyperlipidemia in rats and possibly in man.

PMID- 10956091
TI  - Radical scavenging activity of a purple pigment, hordeumin, from uncooked barley
      bran-fermented broth.
AB  - A novel purple pigment called hordeumin, a type of anthocyanin-tannin pigment,
      was produced from barley bran-fermented broth. The radical scavenging activity of
      hordeumin was analyzed by using an electron-spin resonance (ESR) spectrometer.
      The hordeumin scavenged superoxide radical in a concentration-dependent manner.
      Superoxide dismutase-like activity values were 118 and 195 units/mg for crude and
      partially purified hordeumin, respectively. The two types of hordeumins also
      scavenged the DPPH radical. Furthermore, barley bran-fermented filtrate before
      pigment formation and extract of barley bran also scavenged the DPPH radical.
      However, the DPPH radical scavenging activity of a filtrate, fermented over a
      long period, was stronger than that fermented over a short period. Thus, it was
      considered that radical scavenging activity of hordeumin resulted from barley
      bran polyphenol such as proanthocyanidins.

PMID- 10956092
TI  - Mechanical and structural properties of milk protein edible films cross-linked by
      heating and gamma-irradiation.
AB  - The mechanical properties of cross-linked edible films based on calcium caseinate
      and two type of whey proteins (commercial and isolate) were investigated. Cross
      linking of the proteins was carried out using thermal and radiative treatments.
      Size-exclusion chromatography performed on the cross-linked proteins showed that
      gamma-irradiation increased the molecular weight of calcium caseinate, while it
      changed little for the whey proteins. However, heating of the whey protein
      solution induced cross-linking. For both cross-linked proteins, the molecular
      weight distribution was >/=2 x 10(3) kDa. Combined thermal and radiative
      treatments were applied to protein formulations with various ratios of calcium
      caseinate and whey proteins. Whey protein isolate could replace up to 50% of
      calcium caseinate without decreasing the puncture strength of the films. Films
      based on commercial whey protein and calcium caseinate were weaker than those
      containing whey protein isolate. Electron microscopy showed that the mechanical
      characteristics of these films are closely related to their microstructures.

PMID- 10956093
TI  - Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1.
AB  - A mutant of Bacillus subtilis IMR-NK1, which is used for the production of
      domestic "natto" in Taiwan, produced high fibrinolytic enzyme activity by solid
      state fermentation using wheat bran as medium. In addition, a strong fibrinolytic
      enzyme was purified from the cultivation media. The purified enzyme was almost
      homogeneous, as examined by SDS-PAGE and capillary electrophoresis. The enzyme
      had an optimal pH of 7.8, an optimal temperature of 55 degrees C, and a K(m) of
      0.15% for fibrin hydrolysis. The molecular mass estimated by gel filtration was
      31.5 kDa, and the isoelectric point estimated by isoelectric focusing
      electrophoresis was 8.3. The enzyme also showed activity for hydrolysis of
      fibrinogen, casein, and several synthetic substrates. Among the synthetic
      substrates, the most sensitive substrate was N-succinyl-Ala-Ala-Pro-Phe-pNA. PMSF
      and NBS almost completely inhibited the activity of the enzyme. These results
      indicate that the enzyme is a subtilisin-like serine protease, similar to
      nattokinase from Bacillus natto.

PMID- 10956094
TI  - Identification and antioxidant activity of flavonoid metabolites in plasma and
      urine of eriocitrin-treated rats.
AB  - Eriocitrin, a flavonoid glycoside present in lemon fruit, is metabolized in vivo
      to a series of eriodictyol, methylated eriodictyol, 3,4-dihydroxyhydrocinnamic
      acid, and their conjugates. Plasma antioxidant activity increased following oral
      administration of aqueous eriocitrin solutions to rats. Eriocitrin metabolites
      were found in plasma and renal excreted urine through HPLC and LC-MS analyses.
      Eriocitrin was not detected in plasma and urine, but eriodictyol,
      homoeriodictyol, and hesperetin in their conjugated forms were detected in plasma
      of 4.0 h following administration of eriocitrin. In urine for 24 h, both
      nonconjugates and conjugates of these metabolites were detected. 3,4
      Dihydroxyhydrocinnamic acid, which is metabolized from eriodictyol by intestinal
      bacteria, was detected in slight amounts with each form in 4.0-h plasma and 24-h
      urine. Eriocitrin was suggested to be metabolized by intestinal bacteria, and
      then eriodictyol and 3,4-dihydroxyhydrocinnamic of its metabolite were absorbed.
      Following administration of eriocitrin, plasma exhibited an elevated resistance
      effect to lipid peroxidation. Eriocitrin metabolites functioning as antioxidant
      agents are discussed.

PMID- 10956095
TI  - Detection and quantification of lysozyme in champagne wines.
AB  - We describe here techniques to detect and quantify lysozyme in Pinot noir and
      Chardonnay Champagne wines. Using a dot-blot technique, lysozyme antibodies were
      able to recognize their antigens even when the concentration of lysozyme in wine
      was 75 mg/L. SDS-PAGE was the second technique used. After Coomassie Brilliant
      Blue (CBB) staining or antibody immunostaining was performed, the wine
      originating from the lysozyme-treated must gave only one band corresponding to
      the lysozyme. It is then possible to precisely determine the concentration of
      lysozyme in a must or a wine by densitometric measurement of this band. The
      control wine gave no band with the CBB staining, such as with the immunostaining.
      The quantification of lysozyme with HPLC is another useable technique because the
      lysozyme elution time is largely superior to that of all of the wine compounds.
      In wines, losses of lysozyme were higher when the enzyme was added at one time to
      the must (-34% for the Pinot noir and -37% for the Chardonnay) than when lysozyme
      is added in 2-fold both in the must and in the wine (around -26% for the two
      wines). The lowest diminution is observed when lysozyme was added to the wine
      only (-18%) in comparison to the addition to the must at 300 mg/L (-43%).

PMID- 10956096
TI  - Semiempirical molecular modeling into quercetin reactive site: structural,
      conformational, and electronic features.
AB  - The conformational behavior, molecular geometry and electronic structure of
      quercetin were investigated using the semiempirical AM1 and PM3 methods. Results
      reveal that quercetin has a nonplanar molecular structure, with cross-conjugation
      occurring at the C ring. Calculations were also performed for quercetin radical
      species at the OH groups, showing the presence of three radicals in a narrow
      range of energy. An interpretation of the antioxidative process mechanism,
      exerted by quercetin as a free radical scavenger, relies on two isoenergetic
      radicals with extended electronic delocalization between adjacent rings, also
      having cross-conjugated systems and being affected by the experimental
      environment influencing their relative order.

PMID- 10956097
TI  - Role of cations in the catalysis of thermostable pectinmethylesterase extracted
      from Marsh grapefruit pulp.
AB  - The de-esterification of high methoxyl pectin by thermostable
      pectinmethylesterase (TS-PME) from Marsh grapefruit was studied at pH 7.5, in a
      temperature range between 25 degrees and 50 degrees C and in the presence of
      various cations. Arrhenius plots were constructed for CaCl(2) (5 to 20 mM),
      SrCl(2) (5 to 20 mM), and spermidine (2.5 to 10 mM) added reactions. Enthalpy
      (DeltaH()) and entropy (DeltaS()) of activation changed with cation type and
      concentration. The presence of cations modified the free energy of the resulting
      enzyme/substrate complex. The entropy of activation was positive at all
      concentrations of CaCl(2) studied, and negative in the same concentration range
      with SrCl(2). Reactions with spermidine showed negative entropy of activation at
      concentrations <5 mM and positive values of entropy at higher concentrations.

PMID- 10956098
TI  - Sugar-casein interaction in deuterated solutions of bovine and caprine casein as
      determined by oxygen-17 and carbon-13 nuclear magnetic resonance: a case of
      preferential interactions.
AB  - 17O NMR spectroscopy and (13)C NMR spectroscopy have been used to study the
      mechanism of interaction of sugars with bovine and caprine caseins in D(2)O. The
      (17)O NMR relaxation results showed in all cases an increase in water of
      hydration, as a result of added sugar; this was predominantly associated with
      "trapped" water in the caseins. Analysis of the vir al coefficients, obtained
      from the (17)O relaxation data, suggested that preferential interactions occur in
      the sugar-protein solutions. This could be the result of either sugar binding or
      a solute-solute thermodynamic effect, preferential hydration. The addition of
      sugars to deuterated solutions of bovine casein and caprine casein high in
      alpha(s1)-casein had little or no effect on either line width or chemical shifts
      of the (13)C NMR spectra of these milk proteins. (13)C NMR studies of sucrose, at
      various concentrations (100-300 mM) in the presence of caprine casein high in
      alpha(s1)-casein, showed no changes in either chemical shifts or T(1) values.
      This indicates that the sugar molecules tumble isotropically and therefore
      neither bind to the protein nor affect viscosity in the protein-sugar studies.
      All of these data suggest that the preferential exclusion of the sugar from the
      domain of the caseins results in preferential hydration of the caseins.

PMID- 10956099
TI  - Antimutagens in gaiyou (Artemisia argyi levl. et vant.).
AB  - Antimutagens from gaiyou (Artemisia argyi Levl. et Vant., Compositae) were
      examined. The methanol extract prepared from aerial parts of this plant strongly
      reduced the mutagenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2),
      when Salmonella typhimurium TA98 was used in the presence of the rat liver
      microsomal fraction. The antimutagens were purified chromatographically while
      monitoring the antimutagenic activity against Trp-P-2 with a modified Ames test
      employing a plate method. This purification resulted in the isolation of four
      strong antimutagens, 5,7-dihydroxy-6,3',4'-trimethoxyflavone (eupatilin), 5, 7,4'
      trihydroxy-6,3'-dimethoxyflavone (jaceosidin), 5,7, 4'-trihydroxyflavone
      (apigenin) and 5,7, 4'-trihydroxy-3'-methoxyflavone (chrysoeriol) from the
      methanol extract. These antimutagenic flavones exhibited strong antimutagenic
      activity against not only Trp-P-2 but also against other heterocyclic amines,
      such as 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-1), 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
      (MeIQ), 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3
      methyl-9H-pyrido[2,3-b]indole (MeA(alpha)C) in S. typhimurium TA98. In contrast,
      they did not exhibit antimutagenic activity against benzo[a]pyrene (B[a]P), 4
      nitroquinoline-1-oxide (4-NQO), 2-aminofluorene (2-AF), 2-nitrofluorene (2-NF) or
      furylfuramide (AF-2) in S. typhimurium TA98, or B[a]P, 4-NQO, 2-NF, AF-2, N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) or sodium azide (SA) in Salmonella
      typhimurium TA100, whereas they decreased the mutagenicity caused by aflatoxin
      B(1) (AFB(1)) and 2-aminoanthracene (2-AA) in both of these tester strains.
      Regarding the structure-activity relationship, the tested flavones had distinct
      differences in the intensities of their antimutagenic activities according to the
      differences of their substitution patterns. Namely, the intensity of
      antimutagenic activities against Trp-P-2 decreased in the order of: 5,7,3',4'
      tetrasubstituted flavones (IC(50): <0.1 mmol/plate), 5,7,4'-trisubstituted
      flavones (IC(50): 0.120-0.260 mmol/plate), 5,6,7,3',4'-pentasubstituted flavones
      (IC(50): 0.440-0. 772 mmol/plate). The four isolated flavones were also studied
      regarding their antimutagenic mechanisms with preincubation methods of the
      modified Ames test and emission spectroscopic analysis. The results suggested
      that all isolated flavones were desmutagens which directly inactivated Trp-P-2 or
      inhibited its metabolic activation.

PMID- 10956100
TI  - A DSC study on the gel-sol transition of a starch and hsian-tsao leaf gum mixed
      system.
AB  - Differential scanning calorimetric analysis was performed on the admixture of 4%
      hsian-tsao leaf gum and 8% wheat starch as a function of salt types and
      concentrations. The salt concentrations (C(s)) studied were 5-100 mM for sodium
      and potassium chloride, and 3.4-34 mM for calcium and magnesium chloride. It was
      found that hsian-tsao leaf gum or starch alone did not present a readily
      recognizable exothermic peak or endothermic peak during cooling or heating in
      DSC. However, mixing these two polymers promoted the intermolecular binding and
      subsequent gelation of the mixtures as evidenced by the DSC exothermic and
      endothermic peaks during cooling and heating, respectively. The setting and
      melting temperatures of such a mixed system shifted progressively to higher
      temperatures with increasing concentrations of added salts. It was considered
      that the aggregated mixed polymers formed thermally stable junction zones with
      higher binding energies. The thermal behavior change was more remarkable by the
      addition of K(+) than by Na(+), and by Ca(2+) than by Mg(2+). For monovalent
      cations, the DSC heating and cooling curves showed a single endothermic and
      exothermic peak. For divalent cations at low concentration, the DSC curves showed
      a single peak. However, with sufficient divalent cations, the DSC curves
      eventually developed a bimodal character. A mixed system with sufficient Ca(2+)
      could form firm gel that was difficult to remelt completely upon heating to 130
      degrees C, indicating the possibility of the formation of ionic bonds through
      cross-links with the carboxyl groups in hsian-tsao leaf gum.

PMID- 10956101
TI  - Isolation and characterization of a peanut maturity-associated protein.
AB  - Using reversed-phase high-performance liquid chromatography (RP-HPLC), the peanut
      protein profile was shown to be related to the maturity, drying time, and drying
      procedure of the peanut. Differences were seen between (a) immature and mature
      seeds for untreated and windrow-dried peanuts, (b) untreated and windrow-dried
      peanuts for immature and mature seeds, and (c) windrow- and stackpole-dried
      peanuts. The most pronounced HPLC peak that increased in size as the peanut
      matured and decreased in size with longer drying times was isolated and
      identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      electrospray ionization mass spectrometry to have a molecular weight of 62 500.
      Since maturity is related to the sensory quality of peanuts, this protein may be
      a marker for peanuts that will produce a higher quality flavor when roasted.

PMID- 10956102
TI  - Free polyunsaturated fatty acids cause taste deterioration of salmon during
      frozen storage.
AB  - Increased intensity of train oil taste, bitterness, and metal taste are the most
      pronounced sensory changes during frozen storage of salmon (Refsgaard, H. H. F.;
      Brockhoff, P. B.; Jensen, B. Sensory and Chemical Changes in Farmed Atlantic
      Salmon (Salmo salar) during Frozen Storage. J. Agric. Food Chem. 1998a, 46, 3473
      3479). Addition of each of the unsaturated fatty acids: palmitoleic acid (16:1, n
      - 7), linoleic acid (C18:2, n - 6), eicosapentaenoic acid (EPA; C20:5, n - 3) and
      docosahexaenoic acid (DHA; C22:6, n - 3) to fresh minced salmon changed the
      sensory perception and increased the intensity of train oil taste, bitterness,
      and metal taste. The added level of each fatty acid ( approximately 1 mg/g salmon
      meat) was equivalent to the concentration of the fatty acids determined in salmon
      stored as fillet at -10 degrees C for 6 months. The effect of addition of the
      fatty acids on the intensity of train oil taste, bitterness and metal taste was
      in the order: DHA > palmitoleic acid > linoleic acid > EPA. Formation of free
      fatty acids was inhibited by cooking the salmon meat before storage. Furthermore,
      no changes in phospholipid level were observed during frozen storage. The results
      suggest that enzymatic hydrolysis of neutral lipids plays a major role in the
      sensory deterioration of salmon during frozen storage.

PMID- 10956103
TI  - Effect of transglutaminase treatment on the glass transition of soy protein.
AB  - The effect of microbial transglutaminase (MTG) treatment on the glass transition
      temperature (T(g)) of two fractions which were isolated from a soy protein sample
      was studied. The T(g) of each fraction measured by differential scanning
      calorimetry was lowered by the MTG treatment, which generated cross-links in the
      samples, and this result agreed with the result of dynamic mechanical analysis.
      From the (1)H NMR measurement, the line width of the (1)H signal of the MTG
      treated sample was observed to be greater than that of the MTG-nontreated sample
      at similar water content, which implied that there was relatively more
      immobilized water in the MTG-treated sample. The MTG treatment seemed to cause
      the increment in immobilized water, which might affect the T(g) of the soy
      protein sample.

PMID- 10956104
TI  - Relationship between the glass transition of soy protein and molecular structure.
AB  - The change in molecular structure of the soy protein samples as a result of the
      microbial transglutaminase treatment was studied using solid-state (13)C NMR
      spectroscopy and circular dichroism (CD), and the relation to the glass
      transition temperature (T(g)) was examined. From NMR measurements, the structure
      of the local region of the C(alpha) methine was observed to change, and the
      region had relatively high mobility. From CD measurements, the structural change
      seemed to be caused by the change in the secondary structure (disintegration of
      the beta-structure). By comparison with the T(g) of another protein, the state of
      the secondary structure of a protein was suggested to be a key in determining its
      T(g).

PMID- 10956105
TI  - Biosynthesis, molecular structure, and domain architecture of potato suberin: a
      (13)C NMR study using isotopically labeled precursors.
AB  - Although suberin in potato wound periderm is known to be a polyester containing
      long-chain fatty acids and phenolics embedded within the cell wall, many aspects
      of its molecular structure and polymer-polymer connectivities remain elusive. The
      present work combines biosynthetic incorporation of site-specifically (13)C
      enriched acetates and phenylalanines with one- and two-dimensional solid-state
      (13)C NMR spectroscopic methods to monitor the developing suberin polymer.
      Exogenous acetate is found to be incorporated preferentially at the carboxyl end
      of the aliphatic carbon chains, suggesting addition during the later elongation
      steps of fatty acid synthesis. Carboxyl-labeled phenylalanine precursors provide
      evidence for the concurrent development of phenolic esters and of monolignols
      typical of lignin. Experiments with ring-labeled phenylalanine precursors
      demonstrate a predominance of sinapyl and guaiacyl structures among suberin's
      phenolic moieties. Finally, the analysis of spin-exchange (solid-state NOESY) NMR
      experiments in ring-labeled suberin indicates distances of no more than 0.5 nm
      between pairs of phenolic and oxymethine carbons, which are attributed to the
      aromatic-aliphatic polyester and the cell wall polysaccharide matrix,
      respectively. These results offer direct and detailed molecular information
      regarding the insoluble intermediates of suberin biosynthesis, indicate probable
      covalent linkages between moieties of its polyester and polysaccharide domains,
      and yield a clearer overall picture of this agriculturally important protective
      material.

PMID- 10956107
TI  - Optimized procedures for analyzing primary alkylamines in wines by
      pentafluorobenzaldehyde derivatization and GC-MS.
AB  - Biogenic primary alkylamines in wines are toxicologically significant and affect
      sensory properties. An optimized method for analysis in wines involving
      derivatization with pentafluorobenzaldehyde (PFB) to corresponding
      pentafluorobenzylimines, liquid-liquid extraction, and gas chromatography with
      mass selective detection is presented. Reaction parameters including pH,
      temperature, time, and derivatizing agent and amine concentration were varied in
      simulated wine solution (15% ethanol) to determine effect on reaction efficiency.
      Optimal reaction efficiency was characterized (pH 12, 24 degrees C, 30 min, and
      10 mg/mL PFB), and parameters were used for the analysis of 10 biogenic
      alkylamines in 12 California wines. Alkylamine concentration in wines ranged from
      0.048 to 91 mg/L. Amine recoveries from wines at five fortification levels (0.1
      85 mg/L) were generally 81-100%.

PMID- 10956106
TI  - MALDI-MS and HPLC quantification of oligosaccharides of lichenase-hydrolyzed
      water-soluble beta-glucan from ten barley varieties.
AB  - This study is the first to apply matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) to both qualitative and quantitative analyses of
      oligosaccharides of lichenase-hydrolyzed water-soluble beta-glucan from barley.
      Compared to high-performance liquid chromatography (HPLC) with an evaporative
      light-scattering detector, MALDI-MS is a rapid technique with high accuracy and
      sensitivity and could be used to assess primary structural features of water
      soluble beta-glucan from different barley varieties.

PMID- 10956108
TI  - Simultaneous determination of beauvericin, enniatins, and fusaproliferin by high
      performance liquid chromatography.
AB  - A rapid, sensitive and inexpensive HPLC method for routine screening of
      beauvericin, fusaproliferin, and enniatin B(1), A(1), and B has been optimized.
      Detection limits were determined, ranging between 0. 5 and 3.6 ng according to
      the compound obtained after spiking samples with each mycotoxin at 10-56
      microg/mL concentration range; recoveries averaging from 56 to 74% were obtained.
      LC-MS conditions for enniatin analyses by API electrospray technique were set up,
      this allowing a unique identification of three different enniatins.

PMID- 10956109
TI  - A rapid method for the quantitative determination of short-chain free volatile
      fatty acids from cheese.
AB  - The determination of free volatile fatty acids (FVFA) is of interest in the
      analysis of cheeses. As these compounds are components of taste and flavor, they
      give indications on metabolic reactions taking place during cheese ripening and
      can provide an evaluation of cheese defects and their causes. One of the most
      widely used methods for the determination of FVFA in cheese involves preliminary
      recovery from the matrix by steam distillation, followed by gas chromatography
      separation. Relatively high distillate volumes must be collected to achieve a
      quantitative yield of all the compounds of interest, so that, as a result, the
      solution is too diluted to achieve good instrumental sensitivity. In this paper,
      an alternative method for the determination of C2-C6 free carboxylic acids in
      cheeses involving the use of a Nukol capillary column and crotonic acid as
      internal standard is described. This method is quick and cheap, as the sample
      preparation is a simple extraction with water. The underivatized FVFA are then
      directly separated by gas chromatography. Using this method, all FVFA in cheeses
      can be quantified with good repeatability and excellent recovery.

PMID- 10956110
TI  - Rapid analysis of essential and branched-chain amino acids in nutraceutical
      products by micellar electrokinetic capillary chromatography.
AB  - A rapid method for the analysis of dansylated essential and branched-chain amino
      acids (BCAAs) by micellar electrokinetic capillary chromatography (MECC) is
      reported. Optimization of analytical conditions has been carried out, evaluating
      the influence on the performance of several parameters such as sodium dodecyl
      sulfate (SDS) concentration in the running electrolyte, temperature, and voltage.
      The effect of the addition of small amounts of isobutanol to the electrolyte has
      also been investigated. The best separation in the shortest time with a 37 cm
      capillary was obtained employing a 20 mM Borax buffer (pH 9.1) + 70 mM SDS at 25
      degrees C and 20 kV. Under these conditions a mixture of nine essential amino
      acids was analyzed in 7 min, while separation of BCAAs occurred in less than 4
      min. Using a shorter capillary (20 cm to the detector), the BCAA separation was
      performed in only 2.5 min. The method was applied to the quantitative analysis of
      amino acids in three commercial nutraceutical preparations. Assessment of
      analytical performance in terms of precision, linearity, and limit of detection
      has also been reported.

PMID- 10956111
TI  - Comparison between HPLC and MALDI-TOF MS analysis of anthocyanins in highbush
      blueberries.
AB  - High-performance liquid chromatography (HPLC) has been widely used as a reliable
      technique to quantify anthocyanins in food samples. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a new
      technique that is having a great impact on food analysis. This study is the first
      to compare HPLC and MALDI-TOF MS quantifications of anthocyanins. The analyses
      were carried out for highbush blueberries at different stages of anthocyanin
      formation. In general, both techniques provided comparable quantitative
      anthocyanin profiles for the samples. HPLC could distinguish anthocyanin isomers,
      whereas MALDI-TOF MS proved to be more rapid in the accurate identification and
      quantification of anthocyanins with different masses. A single MALDI-TOF MS run
      took just 4 min. MALDI-TOF MS analysis can serve as a rapid alternative to HPLC
      for the analysis of anthocyanins in fruits.

PMID- 10956112
TI  - Identification of the clam species Ruditapes decussatus (Grooved carpet shell),
      Venerupis pullastra (Pullet carpet shell), and Ruditapes philippinarum (Japanese
      carpet shell)by PCR-RFLP.
AB  - PCR-RFLP analysis has been applied to the identification of three clam species:
      Ruditapes decussatus (grooved carpet shell), Venerupis pullastra (pullet carpet
      shell), and Ruditapes philippinarum (Japanese carpet shell). PCR amplification
      was carried out using a set of primers designed from the DNA nucleotide sequences
      reported for alpha-actins from humans and various animals. Restriction
      endonuclease analysis based on sequence data of the PCR products of each clam
      species revealed the presence of species-specific polymorphic sites for MaeIII
      and RsaI endonucleases. Electrophoretic analysis of the amplicons digested with
      MaeIII and RsaI produced species-specific profiles that allowed the genetic
      identification of the three clam species.

PMID- 10956113
TI  - In vitro determination of the indigestible fraction in foods: an alternative to
      dietary fiber analysis.
AB  - Dietary fiber (DF) intakes in Western countries only accounts for about one-third
      of the substrates required for colonic bacterial cell turnover. There is a
      general trend among nutritionists to extend the DF concept to include all food
      constituents reaching the colon. In this line, a method to quantify the major
      nondigestible components in plant foods, namely, the indigestible fraction (IF),
      is presented. Analytical conditions for IF determination are close to
      physiological. Samples, analyzed as eaten, were successively incubated with
      pepsin and alpha-amylase; after centrifugation and dialysis, insoluble and
      soluble IFs were obtained. IF values include DF, resistant starch, resistant
      protein, and other associated compounds. IF contents determined in common foods
      (cereals, legumes, vegetables, and fruits) were higher than DF contents.
      Calculated IF intakes were close to the estimated amount of substrates reaching
      the colon. IF data could be more useful than DF data from a nutritional point of
      view; therefore, IF is proposed as an alternative to DF for food labeling and
      food composition tables.

PMID- 10956114
TI  - Rapid detection of meso-diaminopimelic acid in lactic acid bacteria by microwave
      cell wall hydrolysis.
AB  - Two innovative microwave hydrolysis procedures for rapidly detecting meso
      diaminopimelic acid in lactic acid bacteria have been developed. Whole-cell
      hydrolysis was performed both in liquid phase and vapor phase with 6 N HCl in
      sealed vessels using a microwave oven equipped with pressure and temperature
      probes. The presence or absence of meso-diaminopimelic acid determined by TLC,
      after the application of liquid- and vapor-phase microwave hydrolysis procedures,
      gave the same qualitative results as those obtained by traditional hydrolysis.
      These standardized microwave hydrolysis procedures permit a drastic reduction in
      hydrolysis time, from 16-20 h to less than 10 min and, consequently, in the total
      time of meso-diaminopimelic acid analysis (less than 90 min). Microwave
      hydrolysis in vapor phase is particularly convenient because, besides reducing
      hydrolysis time, it also eliminates the successive troublesome step of HCl
      removal.

PMID- 10956116
TI  - Comparison of HPLC and GLC techniques for the determination of the triglyceride
      profile of cocoa butter.
AB  - Current methods for the authentication of cocoa butter (CB) are mainly based on a
      knowledge of its triglyceride (TG) composition. The performances of capillary GLC
      and nonaqueous HPLC with an evaporative light-scattering detector (ELSD) for the
      quantification of TG of CB of different geographical origins were compared. Use
      of capillary columns coated with a polarizable stationary phase or two reversed
      phase HPLC columns coupled in series efficiently separated the major TG species
      contained in CB. The velocity of the GLC carrier gas influenced the FID response
      factors of TG standard compounds, which were linearly related to the retention
      times of the analytes studied. Within a certain mass range the ELSD response of
      standard TG solutions did not deviate from unity to a greater extent, independent
      of the molecular structure of the TG species. The quantities of individual TG as
      obtained by both methods were in close agreement, and the precisions of the
      methods were also of comparable magnitude, so that either method can be applied
      to assess the purity of CB. Capillary GLC has the advantage of higher sample
      throughput due to a shorter run time and because the consumption of chemicals is
      negligible.

PMID- 10956117
TI  - Optimization of extraction conditions for active components in Hypericum
      perforatum using response surface methodology.
AB  - Optimal conditions for extraction of Hypericum perforatum were determined using
      response surface methodology. A 3 x 4 x 4 full factorial design representing
      three extraction temperatures, four extraction times, and four solvent
      concentrations was executed. The overall extraction efficiency was defined by
      comparing either the total extractable material weight or the individual
      component peak area to the peak area of luteolin as internal standard. Of the
      tested variables, the extraction temperature most significantly affected
      extraction efficiency. Higher temperatures gave better extraction efficiencies,
      but high temperature also caused decomposition of hypericin. Within the test
      range, responses for most variables had local maxima. Optimum ranges of time and
      concentration for individual variables were overlaid. Considering all variables,
      optimum ranges for extraction time and extraction solvent concentration (percent
      ethanol in acetone) were 5.0-6.7 h and 44-74% at 23 degrees C, 5.4-6.9 h and 45
      72% at 40 degrees C, and 5.3-5.9 h and 44-69% ethanol in acetone at 55 degrees C,
      respectively.

PMID- 10956115
TI  - Analytical method for the determination of cyromazine and melamine residues in
      soil using LC-UV and GC-MSD.
AB  - A method is reported for the determination of cyromazine and melamine residues in
      soil. Soil samples are extracted twice via mechanical shaking, each time with 70%
      acetonitrile/30% 0.050 M ammomium carbonate for 30 min. An aliquot portion of the
      pooled extracts is subjected to strong cation exchange (SCX) purification on AG
      50W-X4 resin. Final analysis is accomplished using liquid chromatography
      ultraviolet (LC-UV) detection at a wavelength of 214 nm. Confirmatory analyses
      can be performed using gas chromatography-mass selective detection (GC-MSD) in
      the selected ion monitoring (SIM) mode. The limit of detection (LOD) is 2.5 ng
      injected and the limit of quantification (LOQ) is 10 ppb when using LC-UV for the
      analysis of N-cyclopropyl-1,3,5-triazine-2,4, 6-triamine (cyromazine) and 1,3,5
      triazine-2,4,6-triamine (melamine). The LOD is 0.050 ng injected and the LOQ is
      10 ppb when using GC-MSD for confirmatory analyses. The mean procedural
      recoveries were 97 and 95% and the standard deviations were 16 and 11% for
      cyromazine and melamine, respectively (n = 24), when using LC-UV. The mean
      procedural recoveries were 107 and 92% and the standard deviations were 9.9 and
      16% for cyromazine and melamine, respectively (n = 29), when using GC-MSD. The
      method validation study was conducted under U.S. EPA FIFRA Good Laboratory
      Practice Guidelines 40 CFR 160. The method also passed an Independent Laboratory
      Validation (ILV) as per U.S. EPA FIFRA Subdivision N.

PMID- 10956118
TI  - A group-specific microbiological test for the detection of tetracycline residues
      in raw milk.
AB  - The potentiality of using a luminescent Escherichia coli strain for the specific
      detection of tetracycline residues in raw bovine milk was investigated. The
      sensor cells contain a reporter plasmid carrying the bacterial luciferase operon
      of Photorhabdus luminescens under the control of the tetracycline responsive
      control region from transposon Tn10. Incubation of the cells with the sample
      containing tetracyclines increases the light emission of the sensor cells. The
      most sensitive tetracycline detection was achieved in 120 min and by using CDTA
      as a chelating agent in the assay. Heat-treatment of milk before the assay
      decreased the variations in background luminescence signals and in tetracycline
      induced luminescence between different milk samples. The detection limits for
      tetracycline, oxytetracycline, chlortetracycline, doxycycline, methacycline,
      demeclocycline, and minocycline were between 2 and 35 ng/mL. Nontetracycline
      antibiotics did not significantly interfere with the detection of tetracyclines.

PMID- 10956119
TI  - Development of an enzyme-linked immunosorbent assay for the insecticide
      imidacloprid.
AB  - Enzyme-linked immunosorbent assays (ELISAs) were developed for imidacloprid, a
      neonicotinoid insecticide. Haptens were designed in such ways that spacer arms
      were introduced on either the pyridinyl or the imidazolidinyl ring of
      imidacloprid. Two sets of polyclonal antibodies were raised from rabbits
      immunized with two different immunogens and were characterized with an indirect
      ELISA format. Cross-reactivities and effects of organic solvents on the assays
      were evaluated. One set of antibodies shows approximately equal cross
      reactivities to imidacloprid and its major metabolites with half-maximum
      inhibition concentrations (I(50)) of 73-88 ppb. Another is specific to
      imidacloprid with an I(50) of 35 ppb. The assay was initially applied to the
      analysis of imidacloprid in fortified water, coffee cherry, and bean extracts.

PMID- 10956120
TI  - Analysis of neurotoxin 3-N-oxalyl-L-2,3-diaminopropionic acid and its alpha
      isomer in Lathyrus sativus by high-performance liquid chromatography with 6
      aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization.
AB  - A method was developed for the quantitative determination of the neurotoxic
      nonprotein amino acid, 3-N-oxalyl-L-2,3-diaminopropionic acid (beta-ODAP), and
      its nontoxic alpha-isomer, 2-N-oxalyl-L-2, 3-diaminopropionic acid (alpha-ODAP),
      in the plant samples of Lathyrus sativus after derivatization with 6
      aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) by reversed-phase high
      performance liquid chromatography (HPLC). Hippuric acid was used as an internal
      standard. A linear response was recorded in the concentration rang 0.32-32 nmol
      with r > 0.999. The RP HPLC detection limit for both isomers is 1.8 ng. According
      to different experimental needs, a ternary gradient system can be used to
      determine toxin and other nonprotein amino acids. The RP HPLC method and a
      colorimetric method were compared for measuring ODAP.

PMID- 10956121
TI  - Measuring the aromatic potential of Vitis vinifera L. Cv. Sauvignon blanc grapes
      by assaying S-cysteine conjugates, precursors of the volatile thiols responsible
      for their varietal aroma.
AB  - The method presented for measuring the aromatic potential of Sauvignon blanc must
      is based on an assay of the S-cysteine conjugate precursors of three volatile
      thiols involved in the characteristic aroma of wines made from this grape
      variety: 4-mercapto-4-methylpentan-2-one, 4-mercapto-4-methylpentan-2-ol, and 3
      mercaptohexan-1-ol. These compounds were released enzymatically from their
      precursors by percolating the must through an immobilized tryptophanase column
      (EC 4.1.99.1), catalyzing an alpha, beta-elimination reaction on the S-cysteine
      conjugate. The volatile thiols were analyzed by GC-MS, as were the deuterated
      analogues that had been released from synthesized deuterated precursors and were
      added as internal standards. The quantities of volatile thiols released under
      these conditions were proportional to the S-cysteine conjugate content of the
      must.

PMID- 10956122
TI  - Simultaneous determination of nicotinic acid and nicotinamide in cooked sausages.
AB  - A simple and sensitive method for determining simultaneously nicotinic acid and
      nicotinamide content in cooked sausages by ion-pair reversed-phase liquid
      chromatography is described. Samples are extracted with ultrapure water,
      centrifuged, deproteinized with zinc hydroxide, filtered, and chromatographed
      with UV detection at 261 nm on a 25 cm x 4 mm i.d. Spherisorb ODS-2 cartridge
      using as mobile phase a mixture consisting of 5 mM heptanesulfonic acid adjusted
      to pH 3.3 with phosphoric acid and acetonitrile (75:25, v/v). Both vitamins are
      measured on a reversed-phase column with a single ion-pair reagent. Precision of
      the method was 0.5 and 1.0% (within a day) and 2.3 and 4.5% (between days) for
      nicotinic acid and nicotinamide, respectively. The detection limit was 0.300
      mg/100 g. The recovery was >92% of nicotinic acid and nicotinamide added to
      samples of meats. Twenty samples of six different products have been analyzed in
      duplicate. The mean value for nicotinic acid ranged between 0.908 and 1.267
      mg/100 g of fresh weight and for nicotinamide between 1.968 and 2.880 mg/100 g of
      fresh weight.

PMID- 10956123
TI  - Antioxidant activity of dietary polyphenols as determined by a modified ferric
      reducing/antioxidant power assay.
AB  - Most nonenzymatic antioxidant activity (scavenging of free radicals, inhibition
      of lipid peroxidation, etc.) is mediated by redox reactions. The antioxidant (AO)
      activity of polyphenols (PPs), as ferric-reducing power, was determined for the
      first time using a modified FRAP (ferric reducing/antioxidant power) assay.
      Reaction was followed for 30 min, and both Fe(II) standards and samples were
      dissolved in the same solvent to allow comparison. Selected representative PPs
      included flavonoids (quercetin, rutin, and catechin), resveratrol, tannic acid,
      and phenolic acids (gallic, caffeic, and ferulic). Carotenoids (beta-carotene and
      zeaxanthine), ascorbic acid, Trolox, and BHA were included for comparison.
      Equivalent concentration 1 (EC(1)), as the concentration of AO with a reducing
      effect equivalent to 1 mmol/L Fe(II), was used to compare AO efficiency. PPs had
      lower EC(1) values, and therefore higher reducing power, than ascorbic acid and
      Trolox. Tannic acid and quercetin had the highest AO capacity followed by gallic
      and caffeic acids. Resveratrol showed the lowest reducing effect. Carotenoids had
      no ferric reducing ability. Polyphenol's AO efficiency seemed to depend on the
      extent of hydroxylation and conjugation.

PMID- 10956124
TI  - Rapid assay of choline in foods using microwave hydrolysis and a choline
      biosensor.
AB  - A fast procedure for the determination of choline in food was developed by
      coupling a microwave hydrolysis procedure with an O(2)/choline oxidase-based
      electrochemical biosensor. Time and temperature were varied to select the best
      conditions for the microwave hydrolysis. Results have been compared with those
      found by the traditional method, constituted by hydrolysis at 70 degrees C
      followed by enzymatic-colorimetric assay. Data obtained by the biosensor method
      correlated well with the enzymatic-colorimetric assay (R(2) = 0.998). Microwave
      versus traditional hydrolysis gave a good correlation both with the colorimetric
      and with biosensor procedures with a relative error below 6%. The method is
      sensitive and selective enough to be used for a wide variety of food items
      reducing remarkably the analysis time.

PMID- 10956125
TI  - Extraction of natural complex phenols and tannins from grape seeds by using
      supercritical mixtures of carbon dioxide and alcohol.
AB  - Proanthocyanidins are supposed to have some therapeutical properties as
      antioxidants and antineoplasics. Most of the proanthocyanidins, however, are not
      commercialized since their separation from natural sources is either very
      expensive or not well-known. In this work, the feasibility of application of
      mixtures of carbon dioxide and alcohol under supercritical conditions for
      selective extraction of some phenolic compounds from grape seeds has been
      studied, among them some low polymerized proanthocyanidins, their main monomer
      units, (+)-catechin and (-)-epicatechin, and some low molecular weight phenolic
      compounds, like gallic acid. An analytical-scale supercritical fluid extractor,
      whose operation was previously optimized, was used to carry out the experiments.
      A commercial concentrate of complex phenols and tannins from grape seeds was
      subjected to supercritical extraction in order to find the best operation
      conditions before directly extracting defatted milled grape seeds. The solvent
      capacity was found to increase with pressure and with the amount of alcohol used
      as cosolvent as expected. Such variation in solvent capacity could be used for
      design of a selective separation process where individual phenolic compounds or
      groups of them could be obtained. HPLC coupled with two types of detectors, diode
      array and mass spectrometry, was used for tentative identification and
      quantification of complex phenols and tannins in the extracts and in the raw
      materials used for extraction.

PMID- 10956126
TI  - Role of carbonyl compounds in SO(2) binding phenomena in musts and wines from
      botrytized grapes.
AB  - Carbonyl compounds play an important role in musts from botrytized grapes. Some
      of them, such as glyoxal and methylglyoxal, may explain a considerable part of
      bindable SO(2). Others, such as 2- and 5-oxogluconic acids, produced by gluconic
      acid oxidation in proportions respectively from 2.5 per 1 play an interesting
      role as SO(2) binding indicator. Finally, the levels of some compounds such as
      dihydroxyacetone, 5-oxofructose, and delta-gluconolactone in balance with
      gluconic acid are well correlated with SO(2) binding powers and also explain a
      large part of the bindable SO(2) in musts. During alcoholic fermentation, only
      dihydroxyacetone among these three compounds is metabolized by yeast. Thus, two
      compounds present in grapes, delta-gluconolactone and 5-oxofructose, with three
      yeast SO(2)-binding byproducts, ethanal, pyruvic, and 2-oxoglutaric acids,
      explain much of the SO(2) binding power in wines from botrytized grapes.

PMID- 10956127
TI  - Discriminate analysis of roasted coffee varieties for trigonelline, nicotinic
      acid, and caffeine content.
AB  - Arabica and robusta roasted coffees from several geographical origins, in a total
      of 29 samples, were characterized for their contents in caffeine, trigonelline,
      and nicotinic acid by a recently developed HPLC/diode-array detector method. All
      samples were subjected to the same roasting procedure in order to eliminate the
      variations due to this process. Characterization was achieved by applying
      multivariate and nonparametric analysis to the chromatographic results. The two
      coffee varieties were clearly separated by their trigonelline and caffeine
      contents. Nicotinic acid could not be used as a variety discriminate factor.
      There was no association with the geographical origin of the samples.

PMID- 10956128
TI  - Preparative separation of polyphenols from tea by high-speed countercurrent
      chromatography.
AB  - High-speed countercurrent chromatography (HSCCC) was applied to the separation of
      polyphenols from tea leaves (Camellia sinensis L.). The capability of HSCCC to
      isolate pure tea polyphenols from complex mixtures on a preparative scale was
      demonstrated for catechins, flavonol glycosides, proanthocyanidins, and
      strictinin from green and black tea. The purity and identity of isolated
      compounds was confirmed by (1)H NMR and HPLC-ESI-MS/MS. Gram quantities of
      polyphenols from tea can be isolated with the procedure described.

PMID- 10956129
TI  - Reactive oxygen species scavenging activity of Du-zhong (Eucommia ulmoides oliv.)
      and its active compounds.
AB  - The biologically active compounds and free radical-/ or reactive oxygen species
      (ROS)-/ scavenging effect of water extract from Du-zhong (WEDZ) were
      investigated. The WEDZ used included leaves, raw cortex, and roasted cortex. The
      hot water extract of Du-zhong leaves showed marked activity as a ROS scavenger,
      and the scavenging effect was concentration dependent. The extract of roasted
      cortex exhibited a modest scavenging effect on ROS, while the extract of raw
      cortex had the weakest scavenging effect. The scavenging activity of WEDZ on ROS
      was correlated to its protocatechuic acid (PCA) content. The content of PCA in Du
      zhong determined by HPLC followed the order of leaves (17.17 mg/g) > roasted
      cortex (2.99 mg/g) > raw cortex (1.16 mg/g). The inhibitory activity of leaf
      extract of Du-zhong was stronger than that of PCA on the peroxidation of linoleic
      acid at the same concentration of 0.1 mg/mL. The results presented herein
      indicated that extract of Du-zhong could possibly act as a prophylactic agent to
      prevent free radical-related diseases.

PMID- 10956130
TI  - Identification of three triterpenoids in almond hulls.
AB  - Three triterpenoids, betulinic acid, oleanolic acid, and ursolic acid, were
      isolated as their methyl esters (treatment with diazomethane) from diethyl ether
      extracts of almond hulls (Nonpareil variety) using flash chromatography and
      preparative high-performance liquid chromatography. The triterpenoids, which
      comprised approximately 1% of the hulls, were characterized using chromatographic
      and spectroscopic methods. These studies demonstrate that almond hulls are a rich
      source of these triterpenoids, which have reported anti-inflammatory, anti-HIV,
      and anti-cancer activities.

PMID- 10956131
TI  - Polyphenols, condensed tannins, and other natural products in Onobrychis
      viciifolia (Sainfoin).
AB  - An acetone/water extract of the fodder legume Onobrychis viciifolia afforded
      arbutin, kaempferol, quercetin, rutin, afzelin, the branched quercetin-3-(2(G)
      rhamnosylrutinoside), the amino acid L-tryptophan, the inositol (+)-pinitol, and
      relatively high concentrations of sucrose (ca. 35% of extractable material). Acid
      catalyzed cleavage of the condensed tannins with phloroglucinol afforded
      catechin, epicatechin and gallocatechin as the terminal and extender units, but
      epigallocatechin was only present in extender units. The condensed tannins in O.
      viciifolia presumably consist of hetero- and homopolymers containing both
      procyanidin and prodelphinidin units. Comparison of data from the present study
      and the literature suggests that sainfoin tannins have a highly variable
      composition with cis:trans ratios ranging from 47:53 to 90:10 and
      delphinidin:cyanidin ratios from 36:64 to 93:7. The composition of terminal and
      extender units in sainfoin tannins seems to be cultivar specific.

PMID- 10956132
TI  - Monosaccharide composition of sweetpotato fiber and cell wall polysaccharides
      from sweetpotato, cassava, and potato analyzed by the high-performance anion
      exchange chromatography with pulsed amperometric detection method.
AB  - The cell wall materials (CWMs) from sweetpotato (Ipomoea batatas cv. Kokei 14),
      cassava (Manihot esculenta), and potato (Solanum tuberosum cv. Danshaku) and
      commercial sweetpotato fiber as well as their polysaccharide fractions were
      analyzed for sugar composition by the high-performance anion exchange
      chromatography with pulsed amperometric detection (HPAEC-PAD) method. The
      separation of arabinose and rhamnose, and xylose and mannose, by this method has
      been improved using a CarboPac PA 10 column. Pretreatment of the CWMs and
      cellulose fractions with 12 M H(2)SO(4) was required for complete hydrolysis to
      occur. Commercial sweetpotato fiber was found to be mainly composed of glucose
      (88.4%), but small amounts of other sugars were also detected. Among the root
      crops, sweetpotato CWM had the highest amount of pectin and galacturonic acid.
      Fucose was detected only in cassava CWM and its hemicellulose fraction, while
      galactose was present in the highest amount in potato CWM. Among the
      polysaccharide fractions, it was only in the hemicellulose fraction where
      significant differences in the sugar composition, especially in the galactose
      content, were observed among the root crops.

PMID- 10956133
TI  - Cytotoxic saponins from bulbs of Allium porrum L.
AB  - An extensive phytochemical analysis of the saponin content has been undertaken on
      leek, Allium porrum L., sown and collected at different seasons. As a result of
      this investigation, eight saponins (1-8) have been isolated, four of them (5-8)
      being novel compounds. Compounds 5 and 6, possessing the same tetrasaccharide
      moiety of compounds 1 and 3, display very unusual spirostane aglycones, 12
      ketoporrigenin and 2,12-diketoporrigenin (named porrigenin C), respectively,
      recently isolated for the first time as free sapogenin in the same plant.
      Compounds 7 and 8 are rare cholestane bidesmosides possessing a di- and
      trisaccharide residues linked to a polyhydroxycholesterol aglycone, respectively.
      The structures of the isolated compounds have been determined by nondegradative
      spectroscopic analysis, mainly based on NMR. All the eight saponins isolated from
      leek were tested for their cytotoxic activity against two different cell lines in
      vitro, and compounds 1, 2, and 6 resulted particularly active.

PMID- 10956135
TI  - Shelf-life prediction of processed milk by solid-phase microextraction, mass
      spectrometry, and multivariate analysis.
AB  - A technique based on solid-phase microextraction, mass spectrometry, and
      multivariate analysis (SPME-MS-MVA) was used to predict the shelf life of
      pasteurized and homogenized reduced-fat milk and whole-fat chocolate milk sampled
      over a 7 month period. Using SPME-MS-MVA, which is essentially a mass
      spectrometry-based electronic-nose instrument, volatile bacterial metabolites
      were extracted from milk with SPME (Carboxen-PDMS) and injected into a GC
      capillary column at elevated temperature. Mass fragmentation profiles from the
      unresolved milk volatile components were normalized to the intensity of a
      chlorobenzene internal standard mass peak (m/z 112) and subjected to MVA.
      Prediction models based on partial least-squares regression of mass intensity
      lists were able to predict the shelf life of samples to approximately +/-1 day,
      with correlation coefficients greater than 0.98 for the two types of milk
      samples. Using principal component analysis techniques, the procedure was also
      useful for classifying samples that were rendered unpalatable by nonmicrobial
      sources (contamination by copper and sanitizer) as well as by bacteria.

PMID- 10956134
TI  - Volatile chemicals identified in extracts from leaves of Japanese mugwort
      (Artemisia princeps pamp.).
AB  - Extracts from leaves of Japanese mugwort (Artemisia princeps Pamp.) were obtained
      using two methods: steam distillation under reduced pressure followed by
      dichloromethane extraction (DRP) and simultaneous purging and extraction (SPSE).
      A total of 192 volatile chemicals were identified in the extracts obtained by
      both methods using gas chromatography (GC) and gas chromatography-mass
      spectrometry (GC-MS). They included 47 monoterpenoids (oxygenated monoterpenes),
      26 aromatic compounds, 19 aliphatic esters, 18 aliphatic alcohols, 17
      monoterpenes (hydrocarbon monoterpenes), 17 sesquiterpenes (hydrocarbon
      sesquiterpenes), 13 sesquiterpenoids (oxygenated sesquiterpenes), 12 aliphatic
      aldehydes, 8 aliphatic hydrocarbons, 7 aliphatic ketones, and 9 miscellaneous
      compounds. The major volatile constituents of the extract by DRP were borneol
      (10.27 ppm), alpha-thujone (3.49 ppm), artemisia alcohol (2.17 ppm), verbenone
      (1.85 ppm), yomogi alcohol (1.50 ppm), and germacren-4-ol (1.43 ppm). The major
      volatile constituents of the extract by SPSE were 1,8-cineole (8.12 ppm),
      artemisia acetate (4.22 ppm), alpha-thujone (3.20 ppm), beta-caryophyllene (2.39
      ppm), bornyl acetate (2.05 ppm), borneol (1.80 ppm), and trans-beta-farnesene (1.
      78 ppm).

PMID- 10956136
TI  - Effect of some fat replacers on the release of volatile aroma compounds from low
      fat meat products.
AB  - The effect of fat content and carbohydrate fat-replacers on the release of
      volatile odor compounds from beefburger, salami, and frankfurter has been
      investigated. The reduction in fat content in any of the three meat products
      studied resulted in a tendency toward an increase in the quantities of volatiles
      released in the headspace. Tapioca starch and maltodextrin appear to delay the
      release of certain classes of compounds selectively; for instance, tapioca starch
      appears to slow the release of some Maillard products while maltodextrin has a
      similar effect on terpenes. In contrast, oat fiber decreases the release of most
      of the compounds analyzed. Thus, the addition of carbohydrate fat-replacers to
      low-fat meat products could assist the flavor qualities of low-fat meat products
      by slowing down the release of odor compounds.

PMID- 10956137
TI  - Volatiles from roasted byproducts of the poultry-processing industry.
AB  - Volatiles of roasted chicken breast muscle and byproducts, such as backbones,
      breastbones, spent bones, and skin, were investigated. Total volatile
      concentrations ranged from 2030 ppb in the roasted backbones to 4049 ppb in the
      roasted skin. The major classes of volatile compounds detected in roasted samples
      were aldehydes (648-1532 ppb) and alcohols (336-1006 ppb). Nitrogen- and/or
      sulfur-containing compounds were also detected in appreciable quantities (161-706
      ppb) in all samples. For all samples, hexanal and 2-methyl-2-buten-1-ol were
      dominant among the aldehydes and alcohols, respectively. Among the nitrogen- and
      sulfur-containing compounds, Maillard reaction products, such as
      tetrahydropyridazines, piperidines, and thiazoles, were the major contributors to
      the total volatile content in all samples. The composition of volatiles observed
      in roasted byproducts was markedly different from that of the roasted breast
      muscle. Therefore, the blending of the byproducts in appropriate proportions or
      blending of volatile flavor extracts from different byproducts may be necessary
      to obtain an aroma that mimics roasted chicken aroma.

PMID- 10956138
TI  - Formation of volatile branched chain esters in bananas (Musa sapientum L.).
AB  - Substrates controlling the formation of branched chain volatile esters in
      ripening bananas were investigated by the application of alcohol and amino acid
      precursors to whole fruit and tissue samples. The resulting changes in the
      profile of the volatile esters were determined using SPME and GC. These changes
      revealed the selectivity characteristics of the esterification enzyme AAT, the
      availability of acyl CoA's for ester formation, and the role of substrate supply
      on volatile production. The results obtained suggest that substrate supply is a
      major determinant of the quantitative and qualitative composition of the
      resulting aroma profile.

PMID- 10956139
TI  - Sensory and instrumental analyses of volatiles generated during the extrusion
      cooking of oat flours.
AB  - Three batches of oats were extruded under four combinations of process
      temperature (150 or 180 degrees C) and process moisture (14. 5 and 18%). Two of
      the extrudates were evaluated by a sensory panel, and three were analyzed by GC
      MS. Maillard reaction products, such as pyrazines, pyrroles, furans, and sulfur
      containing compounds, were found in the most severely processed extrudates (high
      temperature, low-moisture). These extrudates were also described by the assessors
      as having toasted cereal attributes. Lipid degradation products, such as
      alkanals, 2-alkenals, and 2, 4-alkadienals, were found at much higher levels in
      the extrudates of the oat flour that had been debranned. It contained lower
      protein and fiber levels than the others and showed increased lipase activity.
      Extrudates from these samples also had significantly lower levels of Maillard
      reaction products that correlated, in the sensory analysis, with terms such as
      stale oil and oatmeal. Linoleic acid was added to a fourth oat flour to simulate
      the result of increased lipase activity, and GC-MS analysis showed both an
      increase in lipid degradation products and a decrease in Maillard reaction
      products.

PMID- 10956140
TI  - Apparatus used for small-scale volatile extraction from ethanol-supplemented low
      salt miso and GC-MS characterization of the extracted flavors.
AB  - An extraction apparatus was equipped with a nitrogen-flushing vessel to purge
      volatiles from a 10-g miso prepared solution at 40 degrees C, a reflux condenser
      to recover water, a coiled cold-trap to separate ethanol in advance, and a glass
      lined stainless (GLS) trap filled with Tenax TA for flavor adsorption. Volatiles
      in the GLS tube were released with a thermal desorption device and condensed with
      a Micro-cryo trap prior to connection with GC and GC-MS for characterization.
      After analysis, a broad volatile profile comprising 9 categories of functional
      group and 97 identified compounds was achieved. As affected by ethanol
      supplementation for miso fermentation, most volatiles except alcohols and acetals
      in the low-salt products fermented with 5% NaCl and 7.5% ethanol were higher than
      those in the control products fermented with 9% NaCl and 0% ethanol and the high
      ethanol supplemented products fermented with 5% NaCl and 15% ethanol. It reveals
      that supplementation of ethanol in miso at an appropriate level not only enabled
      a low-salt miso fermentation but also enhanced flavor formation.

PMID- 10956141
TI  - Effect of urea on volatile generation from Maillard reaction of cysteine and
      ribose.
AB  - Urea occurs naturally in many food products, and its presence affects food
      quality. However, little is known about its impact on flavor generation in food
      production. In this study, the urea contents in beef, pork, and chicken were
      determined. The effects of urea and pH on thermal flavor generation were
      investigated using the model system of cysteine with ribose, which was heated to
      the roasting temperature of 180 degrees C for 2 h at pH 5 and pH 8.5. The results
      revealed relatively large amounts of urea in these meats and demonstrated that pH
      affects aroma generation. Volatiles identified from the reaction system of ribose
      and cysteine showed that sulfur-containing compounds such as thiophenes,
      thiazoles, and thiophenethiols were the most abundant compounds. The addition of
      urea into the reaction mixture caused the disappearance or reduction in content
      of some sulfur-containing compounds but resulted in the generation of several
      important nitrogen-containing volatiles, like pyrazine, methylpyrazine, 2,5- (and
      2,6-)dimethylpyrazine and other alkylpyrazines, which are known to elicit roasty,
      nutty flavor notes. A plausible explanation for this phenomenon is that ammonia
      can be released from urea upon heating and the formed ammonia competes with
      hydrogen sulfide to react with Maillard reaction precursors to produce nitrogen
      containing compounds such as alkylpyrazines.

PMID- 10956142
TI  - Quantitative structure-odor relationships of aliphatic esters using topological
      indices.
AB  - Quantitative structure-activity relationships (QSAR) were used in this study to
      relate the structural parameters (electronic, topological, etc.) to the odor of
      27 aliphatic esters previously evaluated by Rossiter. Rossiter used the Hansch
      approach, principal component analysis and comparative molecular field analysis
      (CoMFA) to predict the odor of these esters. Different structural parameters were
      selected, such as topological, physicochemical, and quantum-chemical indices, to
      find an equation to predict the molecular factors that determine the fruit odor
      of these compounds and to compare such results with those obtained by Rossiter.
      Two significant correlation equations were obtained with the following molecular
      descriptors: one with the electrotopological-state index related to the carbon
      atom of the carbonyl group (S(C)(=)(O)), the Kappa index ((2)Kappa), and the
      topological-state index related to the oxygen on the alcoholic side of the
      molecule (T(-)(O)(-)), and the other with (2)Kappa, S(C)(=)(O), and the energy of
      the highest occupied molecular orbital (E(HOMO)). The model found had a good
      predictive ability as established by cross-validation r(2)(cv) values and thus
      can be used to help in the prediction of odor of similar compounds. This method
      is simplier than the methods used by Rossiter and represents a reliable QSAR
      alternative in predicting the fruit odor of such aliphatic esters.

PMID- 10956143
TI  - Development of rancidity in wheat germ analyzed by headspace gas chromatography
      and sensory analysis.
AB  - Wheat germ is susceptible to oxidation due to its high content of unsaturated
      oil. Volatile compounds in stored wheat germ were evaluated using dynamic
      headspace gas chromatography (HS-GC) and sensory analysis. Preliminary
      comparisons were also made between freshly prepared wheat germ and wheat germ
      subjected to microwave heating at 45 and 55 degrees C prior to storage at room
      temperature. The progress of oxidation was followed in untreated wheat germ for 4
      weeks and in heat-treated wheat germ for 7 weeks by HS-GC and sensory evaluation.
      Significant (p < 0.05) changes in rancid odor and flavor were observed in the
      untreated wheat germ after 3 weeks, whereas no corresponding difference was
      observed in the microwave-heated wheat germ after 7 weeks of storage.
      Identification of a total of 36 volatile compounds was performed according to
      their mass spectra and Kovats indices. The major volatiles were hexanal, alpha
      pinene, 1-hexanol, and 3-carene. In addition to analysis of a short period of
      storage, 30 volatile compounds were identified from the headspace of wheat germ
      stored for >1 year.

PMID- 10956144
TI  - Identification of proline-based diketopiperazines in roasted coffee.
AB  - Five proline-based diketopiperazines were identified in water extracts of roasted
      coffee proteins and roasted coffee itself. These are cyclo(pro-ile), cyclo(pro
      leu), cyclo(pro-phe), cyclo(pro-pro), and cyclo(pro-val). The isolation included
      gel chromatography and solvent (CHCl(3)) extraction; in the case of roasted
      coffee brews, polyamide column chromatography was also used. The identification
      was achieved by LC-ESI-MS and -MS/MS by comparison of the retention time and the
      fragmentation pattern with reference compounds. As a second method GC-EI-MS was
      used. By both methods the presence of diketopiperazines in roasted coffee was
      unambiguously verified.

PMID- 10956145
TI  - Influence of the acetification process on phenolic compounds.
AB  - Little is known about the change of phenolic compounds and total phenolic content
      by the acetification process. The aim of this study was to assess the contents of
      selected phenolic compounds of cider and red and white wines in comparison to
      phenolic profiles in corresponding vinegars by using a new HPLC method for the
      simultaneous separation and quantification of polar phenolic acids and less polar
      flavonoids. Identifications were made by retention times and by means of mass
      spectra. Additionally, total phenolic contents of wines and vinegars were
      determined photometrically. The decrease in total phenol content by the
      acetification process was highest for cider vinegars (40%) and lower for red and
      white wine vinegars (13 and 8%, respectively). A decrease in the contents of
      individual phenolic compounds of vinegars from white white and ciders was not
      observed. In contrast, the contents of individual phenolic compounds in red wine
      vinegar decreased approximately 50%.

PMID- 10956146
TI  - Evolution of chlorpyrifos, fenarimol, metalaxyl, penconazole, and vinclozolin in
      red wines elaborated by carbonic maceration of Monastrell grapes.
AB  - The influence of the different steps involved in the wine-making process on the
      disappearance of chlorpyrifos, fenarimol, metalaxyl, penconazole, and vinclozolin
      in red wines elaborated by carbonic maceration of Monastrell grapes was studied.
      The initial levels of the residues in grapes ranged from 0.28 mg/kg (penconazole)
      to 1 mg/kg (chlorpyrifos). Ten days after the beginning of maceration, the
      compound that had decreased least was chlorpyrifos (83% of initial value
      remaining), whereas metalaxyl, the least persistent of the residues, had
      decreased to 49% of its initial value. In the free-run juice, on the other hand,
      the highest percentage remaining corresponded to metalaxyl (10%) and the lowest
      to chlorpyrifos (0. 1%). After pressing, the percentages of initial values
      eliminated in pomace varied from 82.7% for chlorpyrifos to 17.7% for metalaxyl,
      whereas in the press juice the opposite was the case (37% metalaxyl and 2%
      chlorpyrifos remaining). In finished wine, there were residues of all the
      pesticides, with the exception of chlorpyrifos, metalaxyl (21%) being the most
      persistent. The percentages eliminated in the lees varied from 1.5 to 2.5% of the
      initial value.

PMID- 10956147
TI  - Effect of high-pressure treatment on the carotenoid composition and the radical
      scavenging activity of persimmon fruit purees.
AB  - The carotenoid composition of persimmon fruit purees of two cultivars, cvs. Rojo
      Brillante and Sharon, grown in Spain was determined by HPLC to assess the effects
      of high-pressure processing on some sensory (carotenoids), nutritional
      (provitamin A value), and health-related (radical-scavenging capacity)
      parameters. Total carotenoid content was higher in untreated Rojo Brillante puree
      (22. 11 microg g(-)(1)) than in untreated Sharon puree (15.22 microg g(-)(1)).
      Purees of both untreated cultivars showed similar carotenoid patterns after
      saponification with beta-cryptoxanthin, beta-carotene, and zeaxanthin as the main
      pigments. A high content of lycopene was quantified in Rojo Brillante (5.34
      microg g(-)(1)), whereas only traces were detected in Sharon. The provitamin A
      value, reported as retinol equivalents (RE), was in untreated Rojo Brillante
      puree (77 RE/100 g) similar to that of Sharon (75 RE/100 g). Scavenging free
      radical capacity, measured as antiradical efficiency (AE), showed in untreated
      Rojo Brillante puree a value (12.14 x 10(-)(3)) 8.5 times higher than that in
      untreated Sharon (1. 42 x 10(-)(3)). Nonuniform behavior of high-pressure
      treatment was detected. Pressure treatments at 50 and 300 MPa/15 min/25 degrees C
      for Rojo Brillante and at 50 and 400 MPa/15 min/25 degrees C for Sharon increased
      the amount of extractable carotenoids (9-27%), which are related with the
      increase of vitamin A value (75-87 RE/100 g). No correlation with the increase of
      AE (from 1.42 x 10(-)(3) to 16.73 x 10(-)(3) and 19.58 x 10(-)(3)) after some
      pressure treatments (150 and 300 MPa/15 min/25 degrees C) was found.

PMID- 10956148
TI  - Influence of pyrolytic and aqueous-phase reactions on the mechanism of formation
      of Maillard products.
AB  - The influence of the reaction phase on the mechanism of formation of Maillard
      products was studied by comparison of (13)C-label incorporation patterns of the
      common products formed in model systems consisting of labeled glycine and D
      glucoses subjected to both pyrolysis and heating in aqueous solutions. Pyrolysis
      experiments were performed at 250 degrees C for 20 s, and aqueous model systems
      were heated in sealed vials for 3 h at 120 degrees C followed by GC/MS analysis.
      Label incorporation patterns of the following compounds were analyzed: cyclotene,
      furanmethanol, acetylpyrrole, 5-methyl-pyrrole, trimethylpyrazine, acetic acid, 3
      hydroxy-2-butanone, 2,3-butanedione, and 2-methyl-4, 5-dihydro-3(2H)-furanone.
      Although pyrolysis reaction produced higher number of products, however, the
      major pathways of formation of variety of important Maillard products followed
      the same mechanism under both pyrolytic and aqueous systems. Furthermore,
      contrary to literature speculations, 2-methyl-4, 5-dihydro-3(2H)-furanone was
      shown to be formed by ring contraction of 2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)
      pyran-4-one, through benzilic acid rearrangement, followed by decarboxylation.

PMID- 10956149
TI  - Progress of the Maillard reaction and antioxidant action of Maillard reaction
      products in preheated model systems during storage.
AB  - The progress of the Maillard reaction and the effect of Maillard reaction
      products (MRPs) on lipid oxidation in preheated model systems containing
      pregelatinized starch, glucose, lysine, and soybean oil have been studied during
      storage. The samples, either containing all components or excluding one or more
      of them, were heated at 100 degrees C for 90 min and then stored for up to 180
      days at 25 degrees C. Browning indices and lipid oxidation were measured, and the
      results showed that, in samples containing oil, the Maillard reaction had a
      significant rate also at room temperature and confirmed the ability of MRPs to
      retard peroxide formation. Under the conditions adopted the rate of the Maillard
      reaction was increased by the presence of the oil and its oxidation products. The
      antioxidant action of the MRPs was also evaluated using a peroxide scavenging
      test based on crocin bleaching. The results demonstrated that antioxidant
      activity developed with increased browning of the samples.

PMID- 10956150
TI  - Reactions of allyl isothiocyanate with alanine, glycine, and several peptides in
      model systems.
AB  - The nucleophilic addition reactions of allyl isothiocyanate (AITC) with alanine,
      glycine, and five alanine and/or glycine containing di- and tripeptides were
      investigated in model aqueous solutions of pH 6, 8, and 10 at 25 degrees C for 2
      4 weeks. The formation of primary adducts, i.e., N-allylthiocarbamoyl amino acids
      (ATC-amino acids) or ATC-peptides, their transformation products, i.e., 3-allyl-2
      thiohydantoins originating by cyclization of ATC-amino acids or by cleavage of
      ATC-peptides, and several other minor components were observed. The results
      revealed that both addition and cleavage rates rise proportionally to pH, whereas
      the formation of 2-thiohydantoins from ATC-amino acids is controlled by H(3)O(+)
      concentration. Depending on pH, differences in reaction rates of the additions
      are determined by either pK(a)(NH(2)) of amino compounds or electrical effects
      and steric hindrance of the molecules. The latter factors are crucial also for
      differences in cleavage rates of ATC-peptides. With regard to the pK(a) values
      and simultaneous AITC decomposition by aqueous nucleophiles, the reactions with
      amino acids and oligopeptides are predominant reaction pathways of AITC in
      solutions of pH 10 and 8, respectively. Reaction mechanism of the cleavage of 2
      thiohydantoins from ATC-peptides in alkaline and mild acidic solutions is
      different from the conventional Edman scheme used for anhydrous acid medium.

PMID- 10956151
TI  - Effect of extrusion on isoflavone content and antiproliferative bioactivity of
      soy/corn mixtures.
AB  - The present studies were conducted to determine changes in the quantities of
      select isoflavones and in the bioactivity (ability to inhibit proliferation of
      human breast cancer cell lines) of extracts from blends of soy protein and
      cornmeal during extrusion processing. The extrusion of samples resulted in an
      average 24% decrease in the concentration of total isoflavones for all samples.
      Although the amounts of specific genistein-derived and daidzein-derived forms
      changed following extrusion, the content of the aglycones genistein and daidzein
      per g sample generally did not change. The extrusion of samples generally
      resulted in decreased antiproliferative action toward breast cancer cells,
      although antiproliferative activity was not eliminated. Therefore, extrusion of
      soy protein/cornmeal-containing foods are likely to retain a considerable portion
      of their isoflavone content and some of the health benefits associated with soy.

PMID- 10956152
TI  - In vitro antiproliferative activity of isothiocyanates and nitriles generated by
      myrosinase-mediated hydrolysis of glucosinolates from seeds of cruciferous
      vegetables.
AB  - A comparison of the effect of isothiocyanates and nitriles derived from some
      glucosinolates, namely, epi-progoitrin, sinalbin, glucotropaeolin,
      glucocheirolin, and glucoraphenin, on human erythroleukemic in vitro cultured
      cells was studied. Many studies have in fact evidenced that a consumption of
      vegetable containing glucosinolates could reduce the development of colorectal
      cancer. In the experimental conditions used, the production of isothiocyanates
      and nitriles from glucosinolates is almost quantitative as confirmed by HPLC or
      GC-MS analysis. The obtained results demonstrated that in general nitriles are
      considerably less potent than the corresponding isothiocyanates in inhibiting
      cancer cell growth. Particularly, the isothiocyanates inhibitory activity on K562
      cells growth is higher in the case of products derived from epi-progoitrin,
      glucotropaeolin, glucoraphenin, and glucocheirolin; while for nitriles the higher
      activity in inhibiting K562 cells growth is showed by sinalbin-derived product.
      Considering the antiproliferative activity found for isothiocyanates and
      nitriles, further studies will be aimed to the possible application of
      glucosinolate-derived products as chemopreventive cancer agents for the reduction
      of colorectal cancer.

PMID- 10956153
TI  - Genetic selection for enhanced bioavailable levels of iron in bean (Phaseolus
      vulgaris L.) seeds.
AB  - The bioavailability of Fe from 24 select genotypes of bean (Phaseolus vulgaris
      L.) seeds containing a range of concentrations of Fe, myo-inositol pentaphosphate
      plus phytic acid (IP5+IP6), and tannins was studied using a rat model. Bean
      accessions, selected from field trials for their variations in Fe, phytate, and
      tannin seed concentrations, were grown in a greenhouse in nutrient solutions
      radiolabeled with (59)Fe. Mature seeds were autoclaved and lyophilized. Test
      meals (containing 1 g of dried bean, 0.5 g of sucrose, and 1 g of basal Fe
      deficient diet) were fed to marginally Fe-depleted weanling rats over a 3-h
      period; rats were radioassayed in a gamma-spectrometer immediately after feeding
      and daily thereafter for the next 10 d. Radioiron retention data were used to
      calculate percent Fe absorption (i.e., Fe bioavailability) from the meals. Seed
      Fe concentrations ranged from 52 to 157 microg g(-)(1) dry weight. There was a
      tendency to also select for higher Zn concentrations in the beans when selecting
      for high Fe concentrations. The Fe bioavailability to rats from test meals
      depended on the genotype and varied from 53% to 76% of the total Fe. Bean
      genotypes with higher seed Fe concentrations resulted in increased amounts of
      bioavailable Fe to rats. There was no significant correlation between the Fe
      concentration in different bean genotypes and Fe bioavailability to rats
      attributable to variations in IP5+IP6 or tannins, even though these antinutrients
      varied widely (i.e., from 19.6 to 29.2 micromol of IP5+IP6 g(-)(1) and from 0.35
      to 2.65 mg of tannins g(-)(1)) in the test meals. Other unknown seed factors
      (i.e., antinutrients or promoter substances) may be contributing factors
      affecting Fe bioavailability from bean seeds.

PMID- 10956154
TI  - Tannins in tropical browses: effects on in vitro microbial fermentation and
      microbial protein synthesis in media containing different amounts of nitrogen.
AB  - Four species of browses (Acacia angustissima, Acacia salicina, Calliandra
      calothyrsus, andDichrostachys cinerea) were used to study the effect of tannins
      on microbial fermentation and microbial protein synthesis in incubation media
      containing high nitrogen (HN) and low nitrogen (LN) in the presence and absence
      of polyethylene glycol (PEG, MW 6000). The additional nitrogen in HN medium was
      supplied through ammonium bicarbonate. The use of HN medium significantly (P <
      0.05) increased the in vitro gas and short-chain fatty acid (SCFA) production and
      microbial protein synthesis compared to the LN medium. Incubation of tannin
      containing browses alone produced significantly (P < 0.05) lower gas and SCFA
      compared to in the presence of PEG in both HN and LN media. Inclusion of PEG in
      tannin-containing browses significantly (P < 0.05) reduced the molar proportion
      of propionate compared to in its absence. Higher N in the media resulted in 10.4
      and 9.9% increases in in vitro gas and SCFA production, respectively, whereas
      inclusion of PEG to tannin-containing feed to remove the effect of tannins
      increased the in vitro gas and SCFA production by 186 and 195%, respectively,
      indicating that the low fermentation of tannin-containing browses could be due to
      the depressive effects of tannins on microbial activity and only partially
      accounted for by unavailability of N for rumen microbes. Incubation of browses
      with straw significantly (P < 0.05) decreased ammonia nitrogen concentration but
      increased the in vitro gas and SCFA production and microbial protein synthesis
      compared to straw alone.

PMID- 10956155
TI  - Zinc transport in Caco-2 cells and zinc balance in rats: influence of the heat
      treatment of a casein-glucose-fructose mixture.
AB  - The effects of the heat treatment of casein in the presence of glucose-fructose
      on Zn bioavailability were studied. Changes in Zn speciation were compared after
      in vitro digestion of heated (HC) and unheated mixture (C) alone and as part of
      the diet. The uptake and transport of digested soluble Zn was investigated in
      Caco-2 cells grown in bicameral chambers; balance studies were done in rats fed
      diets containing the different samples. After in vitro digestion, the
      precipitated Zn was significantly higher in HC than in C. In assays with Caco-2
      cells, the amount of Zn transferred from the apical to the basolateral chamber
      was significantly greater when the culture medium contained raw or heated casein.
      However, because a larger proportion of Zn was precipitated by in vitro
      digestion, Zn utilization was less efficient in the presence of casein. In
      biological experiments, food efficiency of the heated casein-glucose-fructose
      diet was lower, and feeding this diet increased the urinary Zn excretion and
      lowered Zn absorption and retention. The effects of browning products generated
      during food processing should be taken into account, especially in diets
      containing marginally adequate levels of Zn, to prevent possible deficiency.

PMID- 10956156
TI  - Assessing antioxidant and prooxidant activities of phenolic compounds.
AB  - Methods for determining primary antioxidant activity were evaluated. A beta
      carotene bleaching method and a free radical method using 2, 2-diphenyl-1
      picrylhydrazyl (DPPH(*)) were modified to rapidly test samples for potential
      antioxidant activity. Malonaldehyde production in a linoleic acid emulsion system
      assayed by an HPLC method was also used to determine antioxidant and prooxidant
      activities initiated by a metal catalyst (Cu(2+)). All methods were used to
      assess activity of selected phenolic compounds including several
      anthocyanidins/anthocyanins and selected berry extracts. Most phenolic compounds
      had prooxidant activity at low concentrations, unlike synthetic antioxidants (BHA
      and BHT). Compounds with similar structures exhibited comparable trends in
      antioxidant activity. Antioxidant activity usually increased with an increase in
      the number of hydroxyl groups and a decrease in glycosylation. The antioxidant
      activity of many phenolic compounds and extracts was comparable to those of
      synthetic antioxidants using the beta-carotene bleaching and HPLC methods.

PMID- 10956157
TI  - Genotoxicity study of reaction products of sorbic acid.
AB  - Sorbic acid (E200) and its salts (potassium and calcium sorbate: E202 and E203)
      are allowed for use as preservatives in numerous processed foods. Sorbic acid has
      a conjugated system of double bonds which makes it susceptible to nucleophilic
      attack, sometimes giving mutagenic products. Under conditions typical of food
      processing (50-80 degrees C), we analyzed the cyclic derivatives resulting from a
      double addition reaction between sorbic acid and various amines. Mutagenesis
      studies, involving the Ames test and genotoxicity studies with HeLa cells and
      plasmid DNA, showed that none of the products studied presented either mutagenic
      or genotoxic activities.

PMID- 10956158
TI  - Influence of lipids with and without other cottonseed reserve materials on
      aflatoxin B(1) production by Aspergillus flavus.
AB  - Cottonseed storage lipids (primarily triglycerides), in either crude or refined
      form, were found to support growth and aflatoxin B(1) production by Aspergillus
      flavus. When lipids were removed from ground whole cottonseed by petroleum ether
      extraction, aflatoxin production dropped by more than 800-fold. Reconstitution of
      the lipid-extracted ground whole seed with a crude preparation of cottonseed
      lipids restored aflatoxin production to the previous levels. Fungal utilization
      of the three major cottonseed reserve materials, raffinose, triglycerides
      (refined cottonseed oil), and cottonseed storage protein, was monitored in vitro
      over a 7 day fermentation period. The fermentation medium contained the reserve
      compounds in proportions approximating those found in mature cottonseed. A.
      flavus rapidly converted raffinose to fructose and melibiose, presumably by
      action of invertase, and then hydrolyzed the melibiose. These simple sugars
      apparently supported initial growth and aflatoxin B(1) production. Raffinose and
      the resulting melibiose were nearly exhausted by day 2. Fungal hydrolysis of
      triglycerides began as exhaustion of carbohydrate approached. After day 2, rapid
      catabolism of the released fatty acids began and coincided with glucose
      regeneration through gluconeogenesis, which peaked on day 6. The fungus did not
      preferentially utilize specific fatty acids. A. flavus also produced a number of
      storage metabolites, including arabitol, erythritol, mannitol, and trehalose.
      Mannitol was produced in much higher concentrations than the other storage
      metabolites. Selective use of simple carbohydrates by A. flavus to drive
      aflatoxin production may suggest strategies for reducing vulnerability of
      cottonseed to aflatoxin contamination.

PMID- 10956159
TI  - Screening on the occurrence of ochratoxin A in green coffee beans of different
      origins and types.
AB  - Since to our knowledge no data are available in the literature regarding the
      influence of green coffee type and origin on ochratoxin A (OTA) content,
      determinations were carried out in order to assess the level of OTA contamination
      in green coffee samples of different provenience. A total of 162 samples of green
      coffee beans from various countries (84 from Africa, 60 from America, and 18 from
      Asia) were analyzed for OTA. Both the amount and the variability of OTA levels
      were tested as a function of green coffee provenience. The results showed that
      106 of the overall samples were positive for OTA, with concentration ranging from
      0 to 48 microg/kg (ppb). In particular, it was possible to verify that African
      samples were more contaminated with respect to samples of other origin in terms
      of frequency and level of OTA; the highest concentrations observed were 18 and 48
      microg/kg in two samples from The Congo.

PMID- 10956160
TI  - Two-year toxicity and carcinogenicity study of methyleugenol in F344/N rats and
      B6C3F(1) mice.
AB  - Methyleugenol (MEG) was tested for toxicity/carcinogenicity in a 2-yr
      carcinogenesis bioassay because of its widespread use in a variety of foods,
      beverages, and cosmetics as well as its structural resemblance to the known
      carcinogen safrole. F344/N rats and B6C3F(1) mice (50 animals/sex/dose group)
      were given MEG suspended in 0.5% methylcellulose by gavage at doses of 37, 75, or
      150 mg/kg/day for 2 yr. Control groups (60 rats/sex and 50 mice/sex) received
      only the vehicle. A stop-exposure group of 60 rats/sex received 300 mg/kg/day by
      gavage for 53 weeks followed by the vehicle only for the remaining 52 weeks of
      the study. A special study group (10 animals/sex/species/dose group) were used
      for toxicokinetic studies. All male rats given 150 and 300 mg/kg/day died before
      the end of the study; survival of female rats given 150 mg/kg/day and all treated
      female mice was decreased. Mean body weights of treated male and female rats and
      mice were decreased when compared to control. Area under the curve results
      indicated that greater than dose proportional increases in plasma MEG occurred
      for male 150 and 300 mg/kg/day group rats (6 and 12 month) and male 150 mg/kg/day
      mice (12 month). Target organs included the liver, glandular stomach, forestomach
      (female rats) and kidney, mammary gland, and subcutaneous tissue (male rats).
      Liver neoplasms occurred in all dose groups of rats and mice and included
      hepatoadenoma, hepatocarcinoma, hepatocholangioma (rats only),
      hepatocholangiocarcinoma, and hepatoblastoma (mice only). Nonneoplastic liver
      lesions included eosinophilic and mixed cell foci (rats only), hypertrophy, oval
      cell hyperplasia, cystic degeneration (rats only), and bile duct hyperplasia.
      Mice also exhibited necrosis, hematopoietic cell proliferation, and hemosiderin
      pigmentation. Glandular stomach lesions in rats and mice included benign and
      malignant neuroendocrine tumors, neuroendocrine cell hyperplasia, and atrophy and
      in mice included glandular ectasia/chronic active inflammation. In female rats,
      the forestomach showed a positive trend in the incidences of squamous cell
      papilloma or carcinoma (combined). Male rats also exhibited kidney (renal tubule
      hyperplasia, nephropathy, and adenomacarcinoma), mammary gland (fibroadenoma),
      and subcutaneous tissue (fibroma, fibrosarcoma) lesions. Male rats also exhibited
      malignant mesotheliomas and splenic fibrosis. These data demonstrate that MEG is
      a multisite, multispecies carcinogen.

PMID- 10956161
TI  - Influence of the hapten conjugation site on the characteristics of antibodies
      generated against metabolites of clostebol acetate.
AB  - 4-chloro-androst-4-ene-3,17-dione (CLAD) and 4-chlorotestosterone (clostebol,
      beta-CLT or CLT) were made immunogenic by coupling to protein carriers via the 3
      and 17 positions, respectively. These immunogens were used to elicit polyclonal
      and monoclonal antibodies to CLAD and to clostebol. The antibodies were
      characterized in an enzyme immunoassay for sensitivity and specificity.
      Polyclonal antisera generated through position 17 reacted preferentially with 4
      chlorotestosterone-17-acetate (clostebol acetate, CLTA), 4-chloro-epitestosterone
      (epi-clostebol, 17alpha-clostebol, 17alpha-CLT), and clostebol, whereas
      polyclonal antisera generated through the 3 position almost did not react with
      these derivatives. Interestingly, the monoclonal antibody generated through the 3
      position recognized (35%) epi-clostebol. These results suggest that polyclonal
      antisera generated through the 17 position have a broad specificity profile and
      can be used to analyze by immunoassay methods urinary metabolites of clostebol
      acetate and thereby detect the illegal use of clostebol acetate in livestock
      farming.

PMID- 10956162
TI  - Insecticidal sesquiterpene from Alpinia oxyphylla against Drosophila
      melanogaster.
AB  - In the course of screening for novel naturally occurring insecticides from
      Chinese crude drugs, an MeOH extract of Alpinia oxyphylla was found to possess
      insecticidal activity against larvae of Drosophila melanogaster Meigen. From the
      extract, an insecticidal compound was isolated by bioassay-guided fractionation
      and identified as nootkatone (1) by GC, GC-MS, and (1)H and (13)C NMR
      spectroscopy. In bioassays for insecticidal activity, 1 showed an LC(50) value of
      11.5 micromol/mL of diet against larvae of D. melanogaster and an LD(50) value of
      96 microg/adult against adults. Epinootkatol (1A), however, showed slight
      insecticidal activity in both assays, indicating that the carbonyl group at the 2
      position in 1 was the important function for enhanced activity of 1.

PMID- 10956163
TI  - Avocadofurans and their tetrahydrofuran analogues: comparison of growth
      inhibitory and insecticidal activity.
AB  - The importance of the double bonds in the furan ring of avocadofurans with
      relation to their insecticidal activity was examined. The insecticidal activity
      of two naturally occurring avocadofurans, 2-(pentadecyl)furan and 2
      (heptadecyl)furan, was compared to the toxicity of five tetrahydrofurans with
      alkyl chains at position 2 and varying side chains from 14 to 18 carbons. We
      found that eliminating the sites of unsaturation in the furan ring of
      avocadofurans significantly reduced the detrimental effects on the mortality and
      growth of the generalist insect herbivore Spodoptera exigua. In 7-day bioassays,
      S. exigua larvae were significantly more affected when fed a diet containing
      avocadofurans as compared to a larvae fed diet treated with the analogous
      tetrahydrofurans. Although larvae fed with the tetrahydrofurans showed reduced
      growth as compared to controls, larval mortality was not significantly increased.
      We conclude that the double bonds in the furan ring of avocadofurans play an
      important role in their insecticidal effects.

PMID- 10956164
TI  - Fate of (14)C-labeled carbonyl sulfide on grains and grain fractions.
AB  - 14C-Labeled carbonyl sulfide (COS) was used to measure the amount of sorbed
      fumigant and alteration products on grains. Wheat, paddy rice, polished rice,
      mungbean, and safflower were exposed to a 60 mg L(-)(1) of (14)COS for 7 days and
      then aired for 5 days. Carbonyl sulfide and/or alteration products in sugars,
      protein, starch, amino acids, protopectines, and hemicelluloses were
      undetectable. The total uptakes of radioactivity determined after fractionation
      and also by extraction were in the range of 36-53 ng g(-)(1) COS equiv. The total
      radioactivity determined by autoradiography was below the detection limit of 70
      ng g(-)(1) COS equiv. Radioactivity in the commodities was less than 0.003% of
      all the radioactivity applied. The amount of retained radiolabel was measured in
      three ways. First, biochemical fractions such as lipids and amino acids were
      separated by chromatography, and the activity was determined in each component.
      Second, commodities were crushed and extracted in aqueous acetone until the
      maximum amount of radiolabel was extracted. Third, autoradiography was carried
      out on commodity kernels.

PMID- 10956165
TI  - Controlled release of a herbicide from matrix granules based on solvent
      fractionated organosolv lignins.
AB  - An organosolv (Alcell) lignin was fractionated with both sequential solvent
      extraction and solvent-mixture precipitation using various organic solvent
      systems. The resulting fractionated lignins were used to prepare matrix granules
      with bromacil as a model compound using a melt process. The release rates of
      bromacil in vitro from the granular matrix system were influenced by both the
      lignin used as carrier and the solution fractionation. The variations in release
      rates were related to the high proportion of low-molecular-weight fraction and
      its associated water-soluble lignin in the fractionated lignins. Fickian
      diffusion was a predominant factor in controlling the release of bromacil from
      the matrix granules based on the low-molecular-weight fraction (L(fr1)). For the
      matrix granules based on the other fractionated lignins, the release of bromacil
      was of super-case II transport. The fine structure of the matrix granules before
      and after release was also studied. An unique release pattern of bromacil was
      observed for the matrix granules based on the low-molecular-weight fraction
      (L(fr1)), showing a fast release followed by zero-order release, which was a
      result of remarkable changes in the structure of the matrix granules during the
      course of release.

PMID- 10956166
TI  - Effect of spores of saprophytic fungi on phytoalexin accumulation in seeds of
      frog-eye leaf spot and stem canker-resistant and -susceptible soybean (Glycine
      max L.) cultivars.
AB  - Two saprophytic fungi (Mucor ramosissimus and Rhizopus sp.) were tested for their
      ability to induce phytoalexin production by seeds of frog-eye leaf spot and stem
      canker-resistant and -susceptible soybean (Glycine max L.) cultivars. Only M.
      ramosissimus was shown to elicit a response and qualitative differences in
      phytoalexin accumulation were found between the susceptible and resistant
      cultivars. Glyceollins I, II, and III and glycinol were isolated from the
      susceptible cultivar, whereas Glyceollins I, II, and III, glycinol, glyceocarpin,
      genistein, isoformononetin, and N-acetyltyramine accumulated in the resistant
      cultivar in response to the same fungal elicitor. Genistein was found to be an
      inducibly formed isoflavonoid instead of a constitutive metabolite in the
      resistant cultivar, whereas N-acetyltyramine is described for the first time as a
      soybean phytoalexin. All the compounds, except genistein, showed fungitoxic
      activity against Cladosporium sphaerospermum. Spectral data of the pterocarpan
      phytoalexins, genistein, and N-acetyltyramine are also given in this work.

PMID- 10956167
TI  - Effect of emulsion size and shelf life of azadirachtin A on the bioefficacy of
      neem (Azadirachta indica A. Juss) emulsifiable concentrates.
AB  - In a study of 33 recipes of neem oil based emulsifiable concentrates, the
      specific surface area of the emulsions and cream plus oil layer separation in
      emulsions at 24 h revealed a correlation of -0.6874 between them and correlations
      of -0.8940 and 0.6972, respectively, with bioefficacy (LC(50)) against the 3-day
      old second-instar larvae of the Bihar hairy caterpillar, Spilosoma obliqua
      Walker. Nearly 96-99% of azadirachtin A in emulsifiable concentrates (aza-A
      content = 617.93-1149.65 ppm) degraded during the heat stability test at 54 +/- 1
      degrees C for 14 days with half-lives ranging between 1.84 and 4.53 days. The
      LC(50) values against S. obliqua were, however, statistically at par in both the
      pre- and the post-heat-treated samples, suggesting a similar effect of
      azadirachtin A and its degradation products on the bioactivity. The half-life of
      azadirachtin A could be enhanced by storing the concentrates at lower
      temperatures. A low pH of the formulation solvent did not check the degradation
      of azadirachtin A, as reported with aqueous solutions in the literature.

PMID- 10956168
TI  - Role of ground trash volatiles in the selection of hibernation sites by boll
      weevils.
AB  - Volatiles play a large role in governing the behavior of boll weevils (Anthonomus
      grandis Boheman). They are attracted to cotton plants, and the female is sexually
      attracted to the male. The attracting compounds in both instances are terpenoids.
      Primarily in the fall of the year, boll weevils seek hibernation sites in leaf
      trash, where they remain until the following spring or summer. In the present
      study, essential oils were prepared by steam distillation from several leaf
      samples known to be prevalent at hibernation sites, and the oils were analyzed by
      GLC-MS. On the basis of the resulting presumptive identifications by comparison
      with those of standards, a number of mixtures were formulated and were field
      tested, as were the essential oils. The field tests failed to support
      unambiguously the premise that boll weevils select hibernation sites on the basis
      of leaf odor alone. However, in the presence of the sex pheromone, beta
      caryophyllene (P > T = 0.08), or a mixture of three sesquiterpene hydrocarbons (P
      > T = 0.10), or a mixture of alkyl alcohols (P > T = 0.15) increased captures.
      The response to formulations of the sex pheromone with beta-caryophyllene may be
      primarily sexual, based on its presence in female boll weevils.

PMID- 10956169
TI  - Structure- and species-dependent insecticidal effects of neo-clerodane
      diterpenes.
AB  - Several natural neo-clerodane diterpenoids isolated from Linaria saxatilis and
      some semisynthetic derivatives were tested against several insect species with
      different feeding adaptations. The antifeedant tests showed that the oliphagous
      Leptinotarsa decemlineata was the most sensitive insect, followed by the aphid
      Myzus persicae. The polyphagous Spodoptera littoralis was not deterred by these
      diterpenoids; however, following oral administration, some of these compounds did
      have postingestive antifeedant effects on this insect. In general terms, the
      antifeedant effects of these compounds were species-dependent and more selective
      than their toxic/postingestive effects. The study of their structure-activity
      relationships showed that both the decalin moiety and the chain at C-9 determined
      their bioactivity. Furthermore, the presence of a 4,18-epoxy/diol moiety was an
      important feature for both the antifeedant and the toxic/postingestive effects.

PMID- 10956170
TI  - Synthesis and biological evaluation of new analogues of the active fungal
      metabolites N-(2-methyl-3-oxodecanoyl)-2-pyrroline and N-(2-methyl-3-oxodec-8
      enoyl)-2-pyrroline (II).
AB  - New analogues of the bioactive enamides isolated from P. brevicompactum (2 and 3)
      have been synthesized to improve the biological activities. Two different
      structural modifications have been introduced: substitution of the aliphatic side
      chain present in the natural products (1-4) by other groups frequently found in
      other active compounds and use of other nitrogen-containing five-membered rings
      with different degrees of oxidation. In this way, the insecticidal and fungicidal
      activities have been improved. Thus, compound 9, which possess a 3-pyrroline
      ring, exhibited important insecticidal activity against third-instar nymphs of
      Oncopeltus fasciatus Dallas (100% mortality at 7.5 microg/cm(2)). Remarkable
      fungicidal activity was also found, and preliminary structure-activity
      relationships could be established.

PMID- 10956171
TI  - Amino- and urea-substituted thiazoles inhibit photosynthetic electron transfer.
AB  - Amino- and urea-substituted thiazoles exhibited in vivo herbicidal activity on
      duckweed (Lemna paucicostata Hegelm. strain 6746) cultures and appeared to act
      via inhibition of photosynthetic electron transport system. A small number of the
      thiazole derivatives tested were active but only at relatively high
      concentrations. The most active structures were the amino-substituted thiazoles
      with isopropyl and n-butyl side chains and the urea-substituted thiazole with p
      chlorophenyl side chain. Decreasing the length of the side chain had a negative
      effect on the PSII inhibitory activity. The urea-substituted series was as a
      group less active than the amino series, and the free acid series had no
      biological activity. The most active compounds competed for the same binding site
      as atrazine on PSII. Computer modeling highlighted the structural similarities
      between some of the thiazoles and the commercial herbicides diuron and atrazine.

PMID- 10956172
TI  - Amelioration of odorous components in spent mushroom compost.
AB  - Volatile sulfur compounds, as well as other volatiles found in the headspace
      above spent mushroom compost (SMC), were analyzed by gas chromatography and mass
      spectrometry. Data from these techniques as well as organoleptic evaluation of
      both the SMC and the chromatographic eluant indicated that the volatile sulfur
      compounds and cresol were important odorous components in SMC; cresol was
      reported as a musty, cattle-feces aroma. Samples consisted of headspaces from
      untreated SMC as well as SMC stirred with 1% (by weight) powered activated carbon
      (PAC). SMC stirred with and without PAC reduced headspace volatile
      concentrations, but the stirred with added PAC further decreased concentrations
      of important malodorants such as volatile sulfur compounds and cresol.

PMID- 10956173
TI  - Beta-glucosidase from Chalara paradoxa CH32: purification and properties.
AB  - The hyphomycete Chalara paradoxa CH32 produced an extracellular beta-glucosidase
      during the trophophase. The enzyme was purified to homogeneity by ion-exchange
      and size-exclusion chromatography. The purified enzyme had an estimated molecular
      mass of 170 kDa by size-exclusion chromatography and 167 kDa by SDS-PAGE. The
      enzyme had maximum activity at pH 4.0-5.0 and 45 degrees C. The enzyme was
      inactivated at 60 degrees C. At room temperature, it was unstable at acidic pH,
      but it was stable to alkaline pH. The purified enzyme was inhibited markedly by
      Hg(2+) and Ag(2+) and also to some extent by the detergents SDS, Tween 80, and
      Triton X-100 at 0.1%. Enzyme activity increased by 3-fold in the presence of 20%
      ethanol and to a lesser extent by other organic solvents. Purified beta
      glucosidase was active against cellobiose and p-nitrophenyl-beta-D
      glucopyranoside but did not hydrolyze lactose, maltose, sucrose, cellulosic
      substrates, or galactopyranoside, mannopyranoside, or xyloside derivatives of p
      nitrophenol. The V(max) of the enzyme for p-NPG (K(m) = 0.52 mM) and cellobiose
      (K(m) = 0.58 mM) were 294 and 288.7 units/mg, respectively. Hydrolysis of pNPG
      was inhibited competitively by glucose (K(i) = 11.02 mM). Release of reducing
      sugars from carboxymethylcellulose by a purified endoglucanase produced by the
      same organism increased markedly in the presence of beta-glucosidase.

PMID- 10956174
TI  - Oxidative degradation of triazine derivatives in aqueous medium: a radiation and
      photochemical study.
AB  - Pulse and steady state radiolysis techniques have been used to determine the
      bimolecular rate constants and to investigate the spectral nature of the
      intermediates and the degradation induced by hydroxyl radicals ((*)OH) with 1,3,5
      triazine (T), 2,4, 6-trimethoxy-1,3,5-triazine (TMT), and 2,4-dioxohexahydro-1,3,
      5-triazine (DHT) in aqueous medium. A competitive kinetic method with KSCN as the
      (*)OH scavenger was used to determine the rate constants for the reaction of
      (*)OH with T, TMT, and DHT. The bimolecular rate constants are 3.4 x 10(9), 2.06
      x 10(8), and 1.61 x 10(9) dm(3) mol(-)(1) s(-)(1) respectively, for T, TMT, and
      DHT at pH approximately 6. The transient absorption spectra obtained from the
      reaction of (*)OH with T, TMT, and DHT have single absorption maxima at 320, 300,
      and 300 nm, respectively, and were found to undergo a second-order decay. The
      formation of TOH(*) [C(6)OH-N(5)-yl radical], TMTOH(*) [N(5)OH-C(6)-yl radical],
      and DHT(*) [C(6)-yl radical] is proposed from the initial attack of (*)OH with T,
      TMT, and DHT, respectively. A complete degradation of TMT (10(-3) mol dm(-3)) was
      obtained after absorbed doses of 5 kGy in N(2)O-saturated solutions and 16 kGy in
      aerated solutions. A similar degradation pattern was obtained with DHT in N(2)O
      saturated solutions. Complete degradation was observed with an absorbed dose of 7
      kGy. On the basis of the results from both pulse and steady state radiolysis, a
      possible reaction mechanism involving (*)OH-mediated oxidative degradation is
      proposed. A complete photodecomposition of DHT was also observed in the presence
      of ferric perchlorate using ultraviolet light at low pH. Photoinduced electron
      transfer between Fe(III) and DHT in the Fe(III)-DHT complex and subsequent
      formation of DHT(*) are proposed to be the major processes that lead to the
      complete degradation of DHT at pH 3.

PMID- 10956175
TI  - Photolytic degradation of florasulam on soil and in water.
AB  - The rate and pathway of degradation in the presence of light for the
      triazolopyrimidine herbicide florasulam was determined on soil and in aqueous
      systems. Florasulam was exposed to natural sunlight for up to 32 days; solar
      irradiance was measured with either chemical actinometers or by radiometry. The
      quantum yield for direct photodegradation in a sterile, buffered aqueous solution
      was determined to be 0.096; an analogous quantum yield for the sum of direct and
      indirect photodegradation on soil was 0.245. The quantum yields were used to
      estimate half-lives due to photodegradation as a function of season and
      temperature. Estimated half-lives due to photodegradation in summer at 40 degrees
      N latitude were 14 days on soil and 36 days in sterile, buffered water.
      Photodegradation was much faster in a natural water system, with a measured half
      life of 3.3 days in summer at 51.5 degrees N latitude, indicating that indirect
      photolytic processes will be important contributors to photodegradation of
      florasulam in aqueous environments.

PMID- 10956176
TI  - Linuron sorption-desorption in field-moist soils.
AB  - Pesticide sorption or binding to soil is traditionally characterized using batch
      slurry techniques. The objective of this study was to determine linuron sorption
      in field-moist or unsaturated soils. Experiments were performed using low-density
      (i.e., 0.25 g mL(-)(1)) supercritical carbon dioxide to remove linuron from the
      soil water phase, thus allowing calculation of sorption coefficients (K(d)) at
      low water contents. Both soil water content and temperature influenced sorption.
      K(d) values increased with increased water content, if less than saturated. K(d)
      values decreased with increased temperature. K(d) values for linuron sorption on
      silty clay and sandy loam soils at 12% water content and 40 degrees C were 3.9
      and 7.0 mL g(-)(1), respectively. Isosteric heats of sorption (DeltaH(i)) were 
      41 and -35 kJ mol(-)(1) for the silty clay and sandy loam soils, respectively.
      The sorption coefficient obtained using the batch method was comparable (K(f) for
      sandy loam soil = 7. 9 microg(1)(-)(1/)(n)() mL(1/)(n)() g(-)(1)) to that
      obtained using the SFE technique. On the basis of these results, pesticide
      sorption as a function of water content must be known to more accurately predict
      pesticide transport through soils.

PMID- 10956177
TI  - Influence of molecular structure on sorption of phenoxyalkanoic herbicides on
      soil and its particle size fractions.
AB  - The sorption and desorption behaviors of four phenoxyalkanoic acid herbicides and
      their metabolites on four agricultural soils and soil particle size fractions
      were examined. Generally, there was a trend of increasing adsorption and
      decreasing desorption in the order mecoprop < MCPA < dichlorprop < 2,4-D. The
      significant increase in adsorption of the phenolic metabolites can be explained
      by their lower polarity and enhanced partition in the organic soil matrix.
      Estimation of sorption distribution coefficients from particle size fraction
      adsorption data was possible for a sandy soil and a silty Cambisol soil only. It
      is suggested that increasing steric demand, for example, molecular volume, and
      slight changes in the polarity of the compounds affect their adsorption
      properties. Comparison of adsorption and desorption data of structurally similar
      compounds obtained from a variety of soils allows investigation of structure
      induced differences in sorption strength.

PMID- 10956178
TI  - Influence of insecticides on microbial transformation of nitrogen and phosphorus
      in Typic Orchragualf soil.
AB  - Four insecticides, viz., BHC, phorate, carbofuran, and fenvalerate, were applied
      at the rate of 7.5, 1.5, 1.0, and 0.35 kg a.i. ha(-)(1), respectively, to
      investigate their effects on the growth and activities of N(2)-fixing and
      phosphate-solubilizing microorganisms in relation to the availability of N and P
      in laterite (Typic Orchragualf) soil. Insecticides in general, and BHC and
      phorate in particular, stimulated the proliferation of aerobic nonsymbiotic N(2)
      fixing bacteria and phosphate-solubilizing microorganisms and also their
      biochemical activities, such as nonsymbiotic N(2)-fixing and phosphate
      solubilizing capacities, which resulted in greater release of available N
      (NH(4)(+) and NO(3)(-)) and P in soil. All the insecticides were persistent in
      soil for a short period of time, and the rate of dissipation was highest for
      fenvalerate followed by phorate, carbofuran, and BHC, depicting the half-lives
      (T(1/2)) 8.8, 9.7, 16.9, and 20.6 days, respectively. The insecticides followed
      first-order reaction kinetics during their dissipation in soil.

PMID- 10956179
TI  - Triflusulfuron-methyl dissipation in water and soil.
AB  - This paper reports laboratory studies of the behavior and fate of triflusulfuron
      methyl in aqueous buffer and soils. Aqueous hydrolysis was pH-dependent and fast
      in acidic buffer solutions. In basic buffers, the hydrolysis rate variation was
      low between pH 7 and pH 10. The degradation pathway in the range of pH 4-10 was
      via cleavage of the sulfonylurea bridge to form two transformation products: 2
      amino-4-(dimethylamino)-6-(2,2,2-trifluoroethoxy)-1,3, 5-triazine (2) and 6
      methyl-2-methylcarboxylate benzene sulfonamide (3). Comparison of transformation
      rates in sterile and nonsterile soils indicates that chemical and microbial
      processes are important in soil degradation. The former is more important in
      acidic soils, and the latter is more important in basic soils. A biphasic model
      fits well with dissipation of triflusulfuron-methyl in soil. The triazine formed
      during the first step of transformation was degraded more rapidly in basic soils
      than in acidic soils.

PMID- 10956180
TI  - Selectivity of Candida antarctica B lipase toward fatty acid and (Iso)propanol
      substrates in esterification reactions in organic media.
AB  - Fatty acid (FA) selectivity of immobilized Candida antarctica B lipase was
      assessed as influenced by various cosubstrate systems for ester synthesis.
      Reaction mixtures contained a homologous series of even-chain n-acyl donor (C(4)(
      )(16)) substrates (FA or their methyl esters, FAME) and a single alcohol
      cosubstrate (propanol, 2-propanol, or their acetate derivatives) in hexane.
      Multiple FA optima were often observed, with preferences for C(6) (or C(4))
      followed by C(14) and sometimes C(10). The degree of selectivity among acyl
      donors was modest (up to 1.28-2.60, based on ratios of selectivity constants) and
      was dependent on the choice of cosubstrate system. Acyl group selectivity ranged
      up to 1.31-1.36 for [FA + alcohol], 1. 48-2.60 for [FAME + alcohol], 1.30-1.72
      for [FA + alcohol acetate], and 1.28-1.88 [FAME + alcohol acetate] reaction
      systems. General shifts in selectivity were observed between short-chain (C(4)(
      )(8)) and long-chain (C(10)(-)(16)) FA as groups with propanol cosubstrate,
      whereas shifts in reaction selectivity were observed toward specific FA(s) for 2
      propanol cosubstrate. Selectivity among a series of alcohol cosubstrates ranged
      up to 13-fold in esterification reactions with C(6) FA.

PMID- 10956181
TI  - DNA identification of commercial ginseng samples.
AB  - An investigation was performed with the objective of developing a DNA-based
      protocol for the identification of commercial samples of the herbal compound
      ginseng. There are currently two major herbal products referred to as ginseng.
      They are Korean or Chinese ginseng (Panax ginseng) and American ginseng (Panax
      quinquefolius). The market for ginseng in the United States is estimated to be
      approximately $300 million annually. Current tests for ginseng species
      identification rely on expert botanical identification of fresh plant/root
      specimens or on biochemical characterization of active and marker compounds
      (e.g., ginsenosides). For the determination of the feasibility of ginseng
      identification by DNA analysis, a strategy based on the direct DNA sequence
      analysis of the nuclear ribosomal internal transcribed spacer region was
      developed. Other genetic tests included sequence analysis of the chloroplast
      ribulose 1,5-bisphosphate carboxylase large subunit gene and DNA fingerprinting
      by the rapid amplification of polymorphic DNA technique. To confirm the results,
      each ginseng sample was identified using high-performance liquid chromatography.
      All methods were successful in distinguishing American from Korean ginseng. In
      addition, the protocol was improved for the isolation of genomic and plastid DNA
      from commercial ginseng preparations by incorporating an impact homogenization
      step into the standard column chromatography purification procedure.

PMID- 10956182
TI  - Cysteine sulfoxides and alliinase activity of some Allium species.
AB  - The flavor precursors of 17 species belonging to the Alliaceae family were
      analyzed by HPLC, and results were evaluated with respect to the classification
      of species into their genus, subgenus, and section. Identification and
      quantification of these precursors were carried out by synthetic and natural
      reference materials. In addition, nine of these species were investigated in
      terms of their alliinase activity. Alliinase (EC 4.4.1.4) catalyzes the
      conversion of odorless (+)-S-alk(en)yl-L-cysteine sulfoxides into volatile
      thiosulfinates. Cysteine sulfoxides as well as alliinase activity were found in
      all investigated samples, and (+)-S-methyl-L-cysteine sulfoxide was most
      abundant. (+)-S-Propyl-L-cysteine sulfoxide was detected in only a few, not
      closely related, species. Analysis of the crude protein extract of nine species
      gave evidence that alliinase activities of samples were similar in terms of pH
      and temperature optimum, K(M) value, and substrate specificity. For all
      investigated protein extracts, the highest specific alliinase activity was found
      for (+)-S-(2-propenyl)-L-cysteine sulfoxide (alliin). The substrate specificity
      of these enzymes was not related to relative abundance of the cysteine
      sulfoxides. However, SDS-PAGE yielded some significant differences among species
      in terms of their total protein compositions. Species belonging to different
      subgenera exhibited a specific protein pattern with molecular masses between 13
      and 35 kDa.

PMID- 10956183
TI  - De novo design of a novel oxazolidinone analogue as a potent and selective
      alpha1A adrenergic receptor antagonist with high oral bioavailability.

PMID- 10956184
TI  - 3,5-Disubstituted-4-hydroxyphenyls linked to 3-hydroxy-2-methyl-4(1H)-pyridinone:
      potent inhibitors of lipid peroxidation and cell toxicity.

PMID- 10956185
TI  - A molecular model for DNA cross-linking by the antitumor agent azinomycin B.
AB  - A computational model for the covalent interstrand DNA cross-linking of the
      antitumor agent azinomycin B is reported and is based on Monte Carlo simulations
      of the four possible monoalkylation species and an examination of the low energy
      conformations of the cross-linked agent. The model was developed using a suitably
      modified version of the AMBER* force field with the experimentally determined
      triplet DNA target sequence 5'-d(GCT)-3' in both the native B-form and containing
      a preformed intercalation site.

PMID- 10956186
TI  - A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of
      drug interactions.
AB  - A ligand-based model is reported that predicts the Ki values for cytochrome P450
      2C9 (CYP2C9) inhibitors. This CoMFA model was used to predict the affinity of 14
      structurally diverse compounds not in the training set and appears to be robust.
      The mean error of the predictions is 6 microM. The experimentally measured Ki
      values of the 14 compounds range from 0.1 to 48 microM. Leave-one-out cross
      validated partial least-squares gives a q2 value of between 0.6 and 0.8 for the
      various models which indicates internal consistency. Random assignment of
      biological data to structure leads to negative q2 values. These models are useful
      in that they establish a pharmacophore for binding to CYP2C9 that can be tested
      with site-directed mutagenesis. These models can also be used to screen for
      potential drug interactions and to design compounds that will not bind to this
      enzyme with high affinity.

PMID- 10956187
TI  - Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors
      with distinct molecular interactions and tumor cell growth inhibition profiles.
AB  - Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1
      and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6
      Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2
      with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and
      formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2
      NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced
      by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values:
      CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells,
      NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7
      microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct
      from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data
      indicate that the distinct mode of binding of NU2058 and NU6027 has direct
      consequences for enzyme and cell growth inhibition.

PMID- 10956188
TI  - Further studies on nociceptin-related peptides: discovery of a new chemical
      template with antagonist activity on the nociceptin receptor.
AB  - Three series of nociceptin (NC)-related peptides were synthesized and their
      abilities (i) to bind to the NC sites expressed in mouse forebrain membranes,
      (ii) to inhibit the electrically evoked contraction of the mouse vas deferens,
      and (iii) to inhibit forskolin-stimulated cAMP accumulation in Chinese hamster
      ovary cells expressing the human recombinant NC receptor (CHONCR) were
      investigated. The compounds of the first series (a series) have an ordinary Xaa1
      Gly2 bond, those of the second series (b series) have a Xaa1psi(CH2-NH)Gly2
      pseudopeptide bond, and those of the third series (c series) have a peptoid
      (Nxaa1-Gly2) structure. The affinity values measured in the binding assay and in
      the two functional assays with the compounds of the three series showed high
      levels of correlation. Thus, (I) the compounds of the a series in which Phe1 was
      substituted with Tyr, Cha, or Leu acted as potent NC receptor agonists; (II) the
      b series compounds behaved as NC receptor antagonists in the mouse vas deferens
      and as full agonists in CHO(NCR) cells with different potencies depending on the
      first amino acid residue, [Phe1psi(CH2-NH)Gly2]NC(1-17)NH2 and [Phe1psi(CH2
      NH)Gly2]NC(1-13)NH2 being the most potent compounds; (III) the compounds of the
      third series were all inactive both as agonists and as antagonists with the
      exception of [Nphe1]NC(1-17)NH2 and [Nphe1]NC(1-13)NH2, which behaved as NC
      receptor antagonists both in the isolated tissue and in CHO(NCR) cells (pKB 6.1
      6.4). In conclusion, this study demonstrates that chemical requirements for NC
      receptor agonists are different from those of antagonists. Moreover,
      modifications of the steric orientation of the aromatic residue Phe1 in the NC
      sequence as obtained with the pseudopeptide bond between Phe1 and Gly2 or with
      the displacement of the benzyl side chain by one atom, as in Nphe1, lead
      respectively to reduction or elimination of efficacy. Indeed, in contrast to
      [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 which has been reported to exhibit agonist
      activity in several assays involving either central or recombinant NC receptors,
      [Nphe1]NC(1-13)NH2 antagonizes the effect of NC at human recombinant NC receptors
      and in the mouse tail withdrawal assay.

PMID- 10956189
TI  - A novel class of highly potent and selective A1 adenosine antagonists: structure
      affinity profile of a series of 1,8-naphthyridine derivatives.
AB  - A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in
      position 2 and various substituents in positions 4 and 7, were synthesized in an
      attempt to obtain potent, selective antagonists for the A1 adenosine receptor
      subtype. The compounds were tested to evaluate their affinity for A1 compared
      with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain
      cortical membranes, most of the compounds showed an affinity for A1 receptors in
      the low nanomolar range and two in the subnanomolar range with an interesting
      degree of A1 versus A2A and A3 selectivity. Comparison of the 4-substituted
      derivatives indicated that 4-OH substitution, with a 4-quinoid structure, causes
      an increase in the A1 and A2A affinity and generally also in A1 selectivity. The
      kind of substitution in position 7 can greatly modulate the affinity: the most
      interesting substituents in this position seemed to be electron-withdrawing
      groups; in particular the 7-chloronaphthyridine 25d showed a remarkable
      selectivity (A2A/A1 ratio of 670, A3/A1 ratio of 14,000) associated with a higher
      A1 affinity (Ki = 0.15 nM). NMR studies on these compounds 12-36 indicated that
      the 4-OH-substituted ones prefer the tautomer in which the oxygen in position 4
      is in the quinoid form and the nitrogen in position 1 is protonated. Theoretical
      calculations are in agreement with the NMR data.

PMID- 10956190
TI  - Structure-activity studies of reduced-size gonadotropin-releasing hormone
      agonists derived from the sequence of an endothelin antagonist.
AB  - We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an
      endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary
      gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a
      GnRH agonistic activity, mediated directly by the GnRH receptor. We now report
      structure-activity studies of peptide I in respect to its interactions with the
      GnRH receptor. Our studies suggest that the bioactive conformation of peptide I,
      recognized by the GnRH receptor, is of a cyclic nature. Thus cyclic analogues of
      peptide I exhibit higher affinity to the GnRH receptor and increased agonistic
      potencies as compared to peptide I itself. A linear peptide, Ile-Ile-Trp-D-Trp
      Leu-Asp, which presumably forms a similar cyclic conformation, was also shown to
      be a GnRH agonist. Intraperitoneal administration of Ac-Ile-Ile-Trp-D-Trp-Leu-Cys
      OH (Ki = 0.32 microM), one of the cyclic hexapeptides that we have synthesized,
      to rats induces secretion of luteinizing hormone (LH) with a potency which is
      only 1 order of magnitude less than that of GnRH itself. Moreover, plasma levels
      of LH remained elevated for a longer period of time following the administration
      of the cyclic hexapeptide. This novel class of GnRH agonists may prove useful in
      the development of new therapeutics.

PMID- 10956191
TI  - Design and synthesis of potent hexapeptide and heptapeptide gonadotropin
      releasing hormone antagonists by truncation of a decapeptide analogue sequence.
AB  - A novel strategy for designing reduced-size analogues of the decapeptide
      gonadotropin-releasing hormone (GnRH) was developed. As opposed to previous
      attempts to delete residues from either of the peptide's termini, our approach is
      based upon the known importance of both C- and N-terminals of GnRH analogues for
      receptor recognition, whereas the central part of the molecule is replaced by a
      short spacer. The present truncation strategy was successful for generation of
      reduced-size hexapeptide and heptapeptide antagonists possessing potent
      antagonistic capacity. The same methodology was not suitable for the generation
      of reduced-size agonists, suggesting different conformational characteristics for
      GnRH agonists and antagonists. A heptapeptide antagonist designed by this method
      was shown to inhibit serum levels of luteinizing hormone in castrated rats in
      vivo. Structure-activity studies suggested that the structural preferences for
      GnRH receptor recognition are similar to those reported for decapeptide
      antagonists. Our studies resulted in a heptapeptide GnRH antagonist (Ac-D-Nal2-D
      Cpa-D-Pal-Gly-Arg-Pro-D-Ala-NH2) with high receptor binding affinity (IC50 = 7
      nM), as compared to that of GnRH itself (IC50 = 2 nM). The highest affinity of a
      hexapeptide antagonist that we have synthesized was somewhat lower (IC50 = 45
      nM).

PMID- 10956192
TI  - Synthesis of novel 5-substituted 3-amino-3,4-dihydro-2H-1-benzopyran derivatives
      and their interactions with the 5-HT1A receptor.
AB  - A series of new enantiomerically pure 3-amino-3,4-dihydro-2H-1-benzopyrans (3
      aminochromans) has been synthesized from (R)- and (S)-5-methoxy-3-amino-3,4
      dihydro-2H-1-benzopyran. The absolute configuration of the respective (R)- and
      (S)-enantiomers was deduced from X-ray crystallography of (R)-3-(N
      isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran, (R)-9a. Various 5
      substituents were introduced via palladium-catalyzed carbonylation of N
      substituted 3-amino-5-trifluoromethanesulfonyloxy-3,4-dihydro-2H-1-benzopyran.
      The effect of N- and 5-substitution on affinity for the 5-HT1A receptor was
      evaluated in competition experiments using rat hippocampal membranes and [3H]8-OH
      DPAT as radioligand. Selected compounds were also tested for their affinity to
      the D1 (rat striatum), D2 (rat striatum), D2A (human cloned), and 5-HT2A (rat
      cortex) receptors. The intrinsic activity of the compounds was evaluated by
      measuring their effect on VIP-stimulated cAMP production in GH4ZD10 cells stably
      transfected with the 5-HT1A receptor. High-affinity compounds with high
      selectivity for the 5-HT1A receptor were found among structures substituted with
      carboxylate esters, amides, and ketones in the 5-position. Primary and secondary
      amines bound with lower affinity than tertiary amines. Larger substituents were
      well-tolerated by the receptor, but the smaller N-ethyl-N-isopropyl bound with
      lower affinity. Generally, the (R)-enantiomers displayed higher affinity for the
      5-HT1A receptor than the corresponding (S)-enantiomers. In the present series of
      compounds, both full and partial agonists were found.

PMID- 10956193
TI  - Synthesis and anticonvulsant activity of novel and potent 6,7
      methylenedioxyphthalazin-1(2H)-ones.
AB  - In this paper, we describe the synthesis of a series of novel substituted 4-aryl
      6,7-methylenedioxyphthalazin-1(2H)-ones. The anticonvulsant activity of these
      compounds against audiogenic seizures was evaluated in DBA/2 mice after
      intraperitoneal (ip) injection. Most of these derivatives are more active than 1
      (4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (1, GYKI
      52466), a well-known noncompetitive AMPA receptor antagonist. As deduced by the
      rotarod test, all the compounds exhibit a toxicity lower than that of 1. Within
      the series of derivatives submitted to investigation, 4-(4-aminophenyl)-2
      butylcarbamoyl-6,7-methylenedioxyphthalazin -1(2H)-one (21) proved to be the most
      active compound and is 11-fold more potent than 1 (i.e., ED50 3.25 micromol/kg
      for 21 versus ED50 35.8 micromol/kg for 1). When compared to 1, compound 21 as
      well as its analogue 4-(4-aminophenyl)-6,7-methylenedioxyphthalazin-1(2H)-one
      (16) show a longer lasting anticonvulsant activity. Compound 21 also effectively
      suppresses seizures induced in Swiss mice by maximal electroshock (MES) and
      pentylenetetrazole (PTZ). Furthermore, it antagonizes in vivo seizures induced by
      2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), 2-amino-3-(3
      hydroxy-5-tert-butyl-isoxazol-4-yl)propionic acid (ATPA), and kainate (KA), and
      its anticonvulsant activity is reversed by pretreatment with aniracetam. Using
      the patch-clamp technique, the capability of derivatives 16 and 21 to antagonize
      KA-evoked currents in primary cultures of granule neurons was tested. They
      behaved as antagonists, but they proved to be less effective than 1 and 1-(4
      aminophenyl)-3,4-dihydro-4-methyl-3-N-methylcarbamoyl-7,8-met hylenedioxy-5H-2,3
      benzodiazepine (2, GYKI 53655) to reduce the KA-evoked currents.

PMID- 10956194
TI  - Ester and amide derivatives of the nonsteroidal antiinflammatory drug,
      indomethacin, as selective cyclooxygenase-2 inhibitors.
AB  - Recent studies from our laboratory have shown that derivatization of the
      carboxylate moiety in substrate analogue inhibitors, such as 5,8,11,14
      eicosatetraynoic acid, and in nonsteroidal antiinflammatory drugs (NSAIDs), such
      as indomethacin and meclofenamic acid, results in the generation of potent and
      selective cyclooxygenase-2 (COX-2) inhibitors (Kalgutkar et al. Proc. Natl. Acad.
      Sci. U.S.A. 2000, 97, 925-930). This paper summarizes details of the structure
      activity studies involved in the transformation of the arylacetic acid NSAID,
      indomethacin, into a COX-2-selective inhibitor. Many of the structurally diverse
      indomethacin esters and amides inhibited purified human COX-2 with ICo5 values in
      the low-nanomolar range but did not inhibit ovine COX-1 activity at
      concentrations as high as 66 microM. Primary and secondary amide analogues of
      indomethacin were more potent as COX-2 inhibitors than the corresponding tertiary
      amides. Replacement of the 4-chlorobenzoyl group in indomethacin esters or amides
      with the 4-bromobenzyl functionality or hydrogen afforded inactive compounds.
      Likewise, exchanging the 2-methyl group on the indole ring in the ester and amide
      series with a hydrogen also generated inactive compounds. Inhibition kinetics
      revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX
      2 and that selectivity is a function of the time-dependent step. Conversion of
      indomethacin into ester and amide derivatives provides a facile strategy for
      generating highly selective COX-2 inhibitors and eliminating the gastrointestinal
      side effects of the parent compound.

PMID- 10956196
TI  - Adenosine kinase inhibitors. 1. Synthesis, enzyme inhibition, and antiseizure
      activity of 5-iodotubercidin analogues.
AB  - Adenosine receptor agonists produce a wide variety of therapeutically useful
      pharmacologies. However, to date they have failed to undergo successful clinical
      development due to dose-limiting side effects. Adenosine kinase inhibitors (AKIs)
      represent an alternative strategy, since AKIs may raise local adenosine levels in
      a more site- and event-specific manner and thereby elicit the desired
      pharmacology with a greater therapeutic window. Starting with 5-iodotubercidin
      (IC50 = 0.026 microM) and 5'-amino-5'-deoxyadenosine (IC50 = 0.17 microM) as lead
      inhibitors of the isolated human AK, a variety of pyrrolo[2,3-d]pyrimidine
      nucleoside analogues were designed and prepared by coupling 5-substituted-4
      chloropyrrolo[2,3-d]pyrimidine bases with ribose analogues using the sodium salt
      mediated glycosylation procedure. 5'-Amino-5'-deoxy analogues of 5-bromo- and 5
      iodotubercidins were found to be the most potent AKIs reported to date (IC50S <
      0.001 microM). Several potent AKIs were shown to exhibit anticonvulsant activity
      in the rat maximal electric shock (MES) induced seizure assay.

PMID- 10956195
TI  - Synthesis and pharmacological evaluation of thiopyran analogues of the dopamine
      D3 receptor-selective agonist (4aR,10bR)-(+)-trans-3,4,4a,10b-tetrahydro-4-n
      propyl-2H,5H [1]b enzopyrano[4,3-b]-1,4-oxazin-9-ol (PD 128907).
AB  - Benzopyranoxazine (+)-7 (PD 128907) is the most dopamine (DA) D3 receptor
      selective agonist presently known. The only structural feature which
      distinguishes 7 from the analogous nonselective naphthoxazines is an oxygen atom
      in the 6-position. To extend this series of tricyclic DA agonists we used a
      classic bioisoster approach and synthesized thiopyran analogues of 7, which have
      a sulfur atom in the 6-position. We prepared trans-4-n-propyl-3,4,4a,10b
      tetrahydro-2H,5H-[1]benzothiopyrano[4, 3-b]-1,4-oxazin-9-ol (9, trans-9-OH
      PTBTO), its enantiomers ((+)-9 and (-)-9), the racemic cis-analogue (10), and the
      racemic trans-sulfoxide (11) and studied the potency and selectivity for DA
      receptors of these compounds. As with other rigid DA agonists, the highest
      affinity for DA receptors resided in one of the enantiomers, in this case the (-)
      enantiomer of 9. On the basis of a single-crystal X-ray analysis of a key
      intermediate, the absolute configuration of (-)-9 was found to be 4aS,10bR, which
      is homochiral with (+)-(4aR,10bR)-7. In contrast to (+)-7 however, (-)-9
      displayed no selectivity for any of the DA receptors. In addition, it has
      affinity for 5HT1A receptors. (+/-)-cis-4-n-Propyl-3,4,4a,10b-tetrahydro-2H,5H
      [1]benzothiopyrano++ +[4,3-b]-1,4-oxazin-9-ol (10), which was expected to be
      inactive, displayed affinity and selectivity for the DA D3 receptor, whereas the
      sulfoxide 11 displayed some DA D3 selectivity, but with a lower affinity. Further
      pharmacological evaluation revealed that (-)-9 is a very potent full agonist at
      DA D2 receptors and a partial agonist at DA D3 receptors. The cis-analogue (+/-)
      10 displayed the same profile, but with lower potency. These findings were
      confirmed in vivo: in reserpinized rats (-)-9 displayed short-acting activation
      of locomotor activity (DA D2 agonism) and also lower lip retraction and flat body
      posture, (5HT1A agonism). Compound (+/-)-10 had no effect on locomotor activity.
      In unilaterally 6-OH-DA lesioned rats, (-)-9 gave short-acting locomotor
      activation. Furthermore, in microdialysis studies in rat striatum, (-)-9 potently
      decreased DA release, confirming its activation of presynaptic DA D2 receptors.

PMID- 10956197
TI  - Adenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure
      activity of diaryltubercidin analogues.
AB  - In the preceding article (Ugarkar et al. J. Med. Chem. 2000, 43) we reported that
      analogues of tubercidin are potent adenosine kinase (AK) inhibitors with
      antiseizure activity in the rat maximum electroshock (MES) model. Despite the
      discovery of several highly potent AK inhibitors (AKIs), e.g., 5'-amino-5'-deoxy-
      5-iodotubercidin (1c) (IC50 = 0.0006 microM), no compounds were identified that
      exhibited a safety, efficacy, and side effect profile suitable for further
      development. In this article, we demonstrate that substitution of the tubercidin
      molecule with aromatic rings at the N4- and the C5-positions not only retains AKI
      potency but also improves in vivo activity. Synthesis of such compounds entailed
      transformation of 4-arylamino-5-iodotubercidin analogues to their corresponding 5
      aryl derivatives via the Suzuki reaction. Alternatively, 4-N-arylamino-5
      arylpyrrolo[2,3-d]pyrimidine bases were constructed and then glycosylated with
      appropriately protected alpha-ribofuranosyl chlorides using a phase-transfer
      catalyst. Several compounds exhibited potent activity in the rat MES seizure
      assay with ED50s < or = 2.0 mg/kg, ip, and showed relatively mild side effects.

PMID- 10956198
TI  - Permanently charged chiral 1,4-dihydropyridines: molecular probes of L-type
      calcium channels. Synthesis and pharmacological characterization of methyl(omega
      trimethylalkylammonium) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5
      pyridinedicarboxylate iodide, calcium channel antagonists.
AB  - We report the synthesis of the single enantiomers of permanently charged
      dihydropyridine derivatives (DHPs with alkyl linker lengths of two and eight
      carbon atoms) and their activities on cardiac and neuronal L-type calcium
      channels. Permanently charged chiral 1,4-dihydropyridines and methyl (omega)
      trimethylalkylammonium) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5
      pyridinedicarboxylate iodides were synthesized in high optical purities from (R)
      (-) and (S)-(+)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-+
      ++pyridinecarboxylic acid, obtained by resolution of racemic 1,4-dihydro-2,6
      dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-pyridi necarboxylic acid.
      Competition binding experiments with radioligand [3H]-(+)-PN200-110 and the block
      of whole cell barium currents through L-type calcium channels in GH4C1 cells show
      that the compounds with the eight-carbon alkyl linker optimally block the L-type
      Ca2+ channels, and that the S-enantiomer is more potent than the R-enantiomer.

PMID- 10956199
TI  - Synthesis and biological evaluation of certain alpha,beta-unsaturated ketones and
      their corresponding fused pyridines as antiviral and cytotoxic agents.
AB  - A new series of 3,5-bis(arylidene)-4-piperidones, as chalcone analogues carrying
      variety of aryl and heteroaryl groups, pyrazolo[4,3-c]pyridines, pyridolo[4,3
      c]pyrimidines, and pyrido[4,3-c]-pyridines, carrying an arylidene moiety, and a
      series of pyrano[3,2-c]pyridines, as flavone and coumarin isosteres, were
      synthesized and screened for their in vitro antiviral and antitumor activities at
      the National Cancer Institute (NCI). Compounds 9 and 18 proved to be active
      against herpes simplex virus-1 (HSV-1), while compound 13 showed moderate
      activity against human immunodeficiency virus-1 (HIV-1). Compounds 14, 26, 28,
      33, and 35 exhibited a broad spectrum antitumor activity. In addition, compounds
      26, 33, and 35 proved to be of moderate selectivity toward leukemia cell lines.
      The pyrano[3,2-c]pyridines heterocyclic system proved to be the most active
      antitumors among the investigated heterocycles.

PMID- 10956200
TI  - ElogPoct: a tool for lipophilicity determination in drug discovery.
AB  - We present an RP-HPLC method, for the determination of logPoct values for neutral
      drugs, which combines ease of operation with high accuracy and which has been
      shown to work for a set of 36 molecules comprised largely of drugs. The general
      features of the method are as follows: (i) compound sparing (< or = 1 mL of a 30
      50 microg/mL solution needed), (ii) rapid determinations (20 min on average),
      (iii) low sensitivity to impurities, (iv) wide lipophilicity range (6 logPoct
      units), (v) good accuracy, (vi) excellent reproducibility. A linear free energy
      relationship (LFER) analysis, based on solvation parameters, shows that the
      method encodes the same information obtained from a shake-flask logPoct
      determination. To the best of our knowledge a similar performance, on a set of
      noncongeneric drugs, has not been previously reported. We refer to the value
      generated via this method as ElogPoct.

PMID- 10956201
TI  - Discovery of novel and potent retinoic acid receptor alpha agonists: syntheses
      and evaluation of benzofuranyl-pyrrole and benzothiophenyl-pyrrole derivatives.
AB  - In the course of our studies on retinoic acid receptor (RAR) agonists, we have
      designed and synthesized a series of benzofuran and benzothiophene derivatives.
      Some of these compounds (1a,b,e,f,j) markedly inhibited LPS-induced B-lymphocyte
      proliferation and exerted RARalpha selectivity. One of them, 4-[5-(4,7
      dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid (1b), when orally administered
      significantly inhibited mouse antibody production and delayed type
      hypersensitivity (DTH) responses from a dose of 0.1 mg/kg.

PMID- 10956202
TI  - Synthesis and evaluation of peptidomimetics as selective inhibitors and active
      site probes of nitric oxide synthases.
AB  - Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L
      citrulline and nitric oxide (NO). Selective inhibition of the isoforms of NOS
      could have great therapeutic potential in the treatment of certain disease states
      arising from pathologically elevated synthesis of NO. Recently, we reported
      dipeptide amides containing a basic amine side chain as potent and selective
      inhibitors of neuronal NOS (Huang, H.; Martasek, P.; Roman, L. J.; Masters, B. S.
      S.; Silverman, R. B. J. Med. Chem. 1999, 42, 3147). The most potent nNOS
      inhibitor among these compounds is L-ArgNO2-L-Dbu-NH2 (1) (Ki = 130 nM), which
      also exhibits the highest selectivity over eNOS (>1,500-fold) with excellent
      selectivity over iNOS (190-fold). Here we describe the design and synthesis of a
      series of peptidomimetic analogues of this dipeptide as potential selective
      inhibitors of nNOS. The biochemical evaluation of these compounds also revealed
      the binding requirements of the dipeptide inhibitors with NOS. Incorporation of
      protecting groups at the N-terminus of the dipeptide amide 1 (compounds 4 and 5)
      resulted in dramatic decreases in the inhibitory potency of nNOS. Masking the NH
      group of the peptide bond (peptoids 6-8 and N-methylated compounds 9-11) also
      gave much poorer nNOS inhibitors than 1. Both of the results demonstrate the
      importance of the alpha-amine of the dipeptide and the NH moiety of the peptide
      bond for binding at the active site. Modifications at the C-terminus of the
      peptide included converting the amide to the methyl ester (12), tert-butyl ester
      (13), and carboxylic acid (14) and also descarboxamide analogues (15-17), which
      revealed less restricted binding requirements for the C-terminus of the
      dipeptide. Further optimization should be possible when we learn more about the
      binding requirements at the active sites of NOSs.

PMID- 10956203
TI  - Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3
      diols and 2-aminoethanols.
AB  - A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated
      for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin
      allograft. A phenyl ring was introduced into the alkyl chain of the lead compound
      3, which is an immunosuppressive agent structurally simplified from myriocin (1,
      ISP-I) via compound 2. The potency of the various compounds was dependent upon
      the position of the phenyl ring within the alkyl side chain. The most suitable
      length between the quaternary carbon atom and the phenyl ring was two carbon
      atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated
      for their T-cell-decreasing effect and immunosuppressive effect using a popliteal
      lymph node gain assay in rats. The absolute configuration at the quaternary
      carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6
      was essential for potent immunosuppressive activity. Favorable substituents for
      the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and
      hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4
      octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess
      considerable activity and is expected to be useful as an immunosuppressive drug
      for organ transplantation.

PMID- 10956204
TI  - Novel mutual prodrug of retinoic and butyric acids with enhanced anticancer
      activity.
AB  - Acyloxylalkyl esters of retinoic acid and small carboxylic acids (C3-5) were
      evaluated for anticancer activity. The derivative of butyric acid (BA) and all
      trans-retinoic acid (ATRA)-retinoyloxymethyl butyrate (RN1)-acting as a mutual
      prodrug was a more potent inducer of cancer cell differentiation and inhibitor of
      proliferation than the parent acids. ED50 of RN1 for differentiation induction in
      HL-60 was over 40-fold lower than that of ATRA. The differentiating activity of
      ATRA compared to that of the acyloxylalkyl esters derived from butyric (RN1),
      propionic (RN2), isobutyric (RN3), and pivalic (RN4) acids was found to be: RN1 >
      RN2 > RN3 > ATRA approximately RN4. This observation implies that the activity of
      the prodrugs depends on the specific acyl fragment attached to the retinoyl
      moiety, and the butyroyl fragment conferred the highest potency. The IC50 values
      for inhibition of Lewis lung (3LLD122) and pancreatic (PaCa2) carcinoma cell line
      colony formation elicited by RN1 were significantly higher than those of ATRA. In
      addition to its superiority over ATRA or BA as growth inhibitors of the above
      cell lines, RN1 was also able to overcome the resistance to ATRA in 3LLD122
      cells.

PMID- 10956205
TI  - Identification of a chemical tool for the orphan nuclear receptor FXR.

PMID- 10956207
TI  - 2-Carbomethoxy-3-aryl-8-bicyclo[3.2.1]octanes: potent non-nitrogen inhibitors of
      monoamine transporters.
AB  - Cocaine is a potent central nervous system stimulant with severe addiction
      liability. Its reinforcing and stimulant properties derive from inhibition of
      monoamine transport systems, in particular the dopamine transporter (DAT). This
      inhibition results in an increase in synaptic dopamine with subsequent
      stimulation of postsynaptic dopamine receptors. A wide variety of ligands
      manifest potent inhibition of the DAT, and these ligands include 3-aryltropane as
      well as 8-oxa-3-aryltropane analogues of cocaine. There has been considerable
      effort to determine structure-activity relationships of cocaine and congeners,
      and it is becoming clear that these inhibitors do not all interact with the DAT
      in the same manner. The functional role of the 8-heteroatom is the focus of this
      study. We describe the preparation and biology of a series of 2-carbomethoxy-3
      arylbicyclo[3.2.1]octane analogues. Results show that methylene substitution of
      the amine or ether function of the 8-hetero-2-carbomethoxy-3
      arylbicyclo[3.2.1]octanes yields potent inhibitors of monoamine transport.
      Therefore neither nitrogen nor oxygen are prerequisites for binding of tropane
      like ligands to monoamine transporters.

PMID- 10956208
TI  - Nonpeptide analogues of dynorphin A(1-8): design, synthesis, and pharmacological
      evaluation of kappa-selective agonists.
AB  - Two novel series of kappa opioid receptor agonist analogues of MPCB-GRRI and MPCB
      RRI, hybrid ligands of MPCB ((-)-cis-N-(2-phenyl-2-carbomethoxy)cyclopropylmethyl
      N-normetazocine ) and of the C-terminal fragments of dynorphin A(1-8), have been
      synthesized. The critical functional groups of the peptide fragments of hybrid
      compounds were maintained, and the binding affinities and selectivities for
      compounds 1-40 to mu, delta, and kappa opioid receptors were analyzed. Compounds
      15 and 16, MPCB-Gly-Leu-NH-(CH(2))(n)()-NH-C(=NH)-C(4)H(9) (n = 5, 6), displayed
      high affinity and selectivity for kappa opioid receptors (K(i)(kappa) = 6.7 and
      5.3 nM, K(i)(mu)/K(i)(kappa) = 375 and 408, and K(i)(delta)/K(i)(kappa) = 408 and
      424, respectively). Since kappa agonists may also cause psychotomimetic effects
      by interaction with sigma sites, binding assays to sigma(1) sites were performed
      where compounds 15 and 16 showed negligible affinity (K(i) > 10 000). Compounds
      15 and 16 were further characterized in vivo and showed potent antinociceptive
      activity in mouse abdominal constriction tests (ED(50) = 0.88 and 1.1 mg/kg,
      respectively), fully prevented by nor-BNI. Thus, these novel analogues open an
      exciting avenue for the design of peptidomimetics of dynorphin A(1-8).

PMID- 10956206
TI  - 3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor
      regulator.
AB  - A series of bis(trifluoromethyl)pyrazoles (BTPs) has been found to be a novel
      inhibitor of cytokine production. Identified initially as inhibitors of IL-2
      synthesis, the BTPs have been optimized in this regard and even inhibit IL-2
      production with a 10-fold enhancement over cyclosporine in an ex vivo assay.
      Additionally, the BTPs show inhibition of IL-4, IL-5, IL-8, and eotaxin
      production. Unlike the IL-2 inhibitors, cyclosporine and FK506, the BTPs do not
      directly inhibit the dephosphorylation of NFAT by calcineurin.

PMID- 10956210
TI  - DoMCoSAR: a novel approach for establishing the docking mode that is consistent
      with the structure-activity relationship. Application to HIV-1 protease
      inhibitors and VEGF receptor tyrosine kinase inhibitors.
AB  - DoMCoSAR is a novel approach for statistically determining the docking mode that
      is consistent with a structure-activity relationship. The approach establishes
      the binding mode for the compounds in a chemical series with the assumption that
      all molecules exhibit the same binding mode. It involves three stages. In the
      first stage all molecules that belong to a given chemical series are docked to
      the active site of the protein target. The only bias used in the docking at this
      stage involves the location of the protein binding site. Coordinates of the
      common substructure (CS) that results from the unbiased docking are then
      clustered to establish the major substructure docking modes. In the second stage
      all molecules are docked to the major docking modes (MDMs) with constraints based
      on the common substructure. The third stage generates, for the major docking
      modes, interaction-based descriptors that include electrostatic, VDW, strain, and
      solvation contributions. The problem of docking mode evaluation is now reduced to
      the question of which descriptor set is more predictive. To establish a
      quantitative comparison of the descriptor sets associated with the major docking
      modes, we use 50 instances of random 4-fold cross-validation. For each 4-fold
      cross-validation the predictive squared correlation coefficient (R(2)) is
      computed. t-Tests are applied to establish significance of the differences in
      mean R(2) for one docking mode versus another. We test the methodology on two
      test cases: HIV-1 protease inhibitors (Holloway et al. J. Med. Chem. 1995, 38,
      305-317) and vascular endothelial growth factor (VEGF) receptor tyrosine kinase
      oxoindoles (Sun et al. J. Med. Chem. 1998, 41, 2588-2603). For both test cases
      there is statistically significant preference for the binding mode consistent
      with the X-ray structure. The appeal of this methodology is that researchers gain
      the objectivity of statistical justification for the selected docking mode. The
      methodology is relatively insensitive to subtle variations of the protein
      structure that include, but are not limited to, side chain and small backbone
      rearrangement during binding. In addition, predictive models that result from the
      approach can be used to further optimize chemical series.

PMID- 10956209
TI  - CoMFA-based prediction of agonist affinities at recombinant wild type versus
      serine to alanine point mutated D2 dopamine receptors.
AB  - Agonist affinity changes dramatically as a result of serine to alanine mutations
      (S193A, S194A, and S197A) within the fifth transmembrane region of D2 dopamine
      receptors and other receptors for monoamine neurotransmitters. However, agonist
      2D-structure does not predict which drugs will be sensitive to which point
      mutations. Modeling drug-receptor interactions at the 3D level offers
      considerably more promise in this regard. In particular, a comparison of the same
      test set of agonists across receptors differing minimally (point mutations)
      offers promise to enhance the understanding of the structural bases for drug
      receptor interactions. We have previously shown that comparative molecular field
      analysis (CoMFA) can be applied to comparisons of affinity at recombinant D1 and
      D2 dopamine receptors for the same set of agonists, a differential QSAR. Here, we
      predicted agonist K(L) for the same set of agonists at wild type D2 vs S193A,
      S194A, and S197A receptors using CoMFA. Each model used bromocriptine as the
      template. ln(1/K(L)) values for the low-affinity agonist binding conformation at
      recombinant wild type and mutant D2 dopamine receptors stably expressed in C6
      glioma cells were used as the target property for the CoMFA of the 16 aligned
      agonist structures. The resulting CoMFA models yielded cross-validated R(2)
      (q(2)) values ranging from 0.835 to 0.864 and simple R(2) values ranging from
      0.999 to 1.000. Predictions of test compound affinities at WT and each mutant
      receptor were close to measured affinity values. This finding confirmed the
      predictive ability of the models and their differences from one another. The
      results strongly support the idea that CoMFA models of the same training set of
      compounds applied to WT vs mutant receptors can accurately predict differences in
      drug affinity at each. Furthermore, in a "proof of principle", two different
      templates were used to derive the CoMFA model for the WT and S193A mutant
      receptors. Pergolide was chosen as an alternate template because it showed a
      significant increase in affinity as a result of the S193A mutation. In this
      instance both the bromocriptine- and pergolide-based CoMFA models were similar to
      one another but different from those for the WT receptor using bromocriptine- or
      pergolide- as templates. The pergolide-based S193A model was more strikingly
      different from that of the WT receptor than was the bromocriptine-based S193A
      model. This suggests that a "dual-template" approach to differential CoMFA may
      have special value in elucidating key differences across related receptor types
      and in determining important elements of the drug-receptor interaction.

PMID- 10956211
TI  - GRID/CPCA: a new computational tool to design selective ligands.
AB  - We present a computational procedure aimed at understanding enzyme selectivity
      and guiding the design of drugs with respect to selectivity. It starts from a set
      of 3D structures of the target proteins characterized by the program GRID. In the
      multivariate description proposed, the variables are organized and scaled in a
      different way than previously published methodologies. Then, consensus principal
      component analysis (CPCA) is used to analyze the GRID descriptors, allowing the
      straightforward identification of possible modifications in the ligand to improve
      its selectivity toward a chosen target. As an important new feature the
      computational method is able to work with more than two target proteins and with
      several 3D structures for each protein. Additionally, the use of a 'cutout tool'
      allows to focus on the important regions around the active site. The method is
      validated for a total number of nine structures of the three homologous serine
      proteases thrombin, trypsin, and factor Xa. The regions identified by the method
      as being important for selectivity are in excellent agreement with available
      experimental data and inhibitor structure-activity relationships.

PMID- 10956212
TI  - 3-(Hydroxymethyl)-bearing phosphatidylinositol ether lipid analogues and
      carbonate surrogates block PI3-K, Akt, and cancer cell growth.
AB  - Phosphatidylinositol 3-kinase (PI3-K) phosphorylates the 3-position of
      phosphatidylinositol to give rise to three signaling phospholipids. Binding of
      the pleckstrin homology (PH) domain of Akt to membrane PI(3)P's causes the
      translocation of Akt to the plasma membrane bringing it into contact with
      membrane-bound Akt kinase (PDK1 and 2), which phosphorylates and activates Akt.
      Akt inhibits apoptosis by phosphorylating Bad, thus promoting its binding to and
      blockade of the activity of the cell survival factor Bcl-x. Herein we present the
      synthesis and biological activity of several novel phosphatidylinositol analogues
      and demonstrate the ability of the carbonate group to function as a surrogate for
      the phosphate moiety. Due to a combination of their PI3-K and Akt inhibitory
      activities, the PI analogues 2, 3, and 5 proved to be good inhibitors of the
      growth of various cancer cell lines with IC(50) values in the 1-10 microM range.
      The enhanced Akt inhibitory activity of the axial hydroxymethyl-bearing analogue
      5 compared to its equatorial counterpart 6 is rationalized based upon postulated
      differences in the H-bonding patterns of these compounds in complex with a
      homology modeling generated structure of the PH domain of Akt. This work
      represents the first attempt to examine the effects of 3-modified PI analogues on
      these two crucial cell signaling proteins, PI3-K and Akt, in an effort to better
      understand their cell growth inhibitory properties.

PMID- 10956213
TI  - Molecular design, synthesis, and hypoglycemic activity of a series of
      thiazolidine-2,4-diones.
AB  - A series of imidazopyridine thiazolidine-2,4-diones were designed and synthesized
      from their corresponding pyridines. These compounds represent conformationally
      restricted analogues of the novel hypoglycemic compound rosiglitazone (5). The
      series was evaluated for its effect on insulin-induced 3T3-L1 adipocyte
      differentiation in vitro and its hypoglycemic activity in the genetically
      diabetic KK mouse in vivo. The structure-activity relationships are discussed. On
      the basis of the in vivo potency, 5-[4-(5-methoxy-3-methyl-3H-imidazo[4, 5
      b]pyridin-2-ylmethoxy)benzyl]thiazolidine-2,4-dione (19a) was selected as the
      candidate for further studies in a clinical setting.

PMID- 10956214
TI  - Analogues of amonafide and azonafide with novel ring systems.
AB  - Three new types of amonafide and azonafide analogues were synthesized and
      screened in a panel of human solid tumor cells and murine L1210 leukemia cells.
      The structural types included tetrahydroazonafides, which have the naphthalene
      chromophore of amonafide within the anthracene nucleus of azonafide; phenanthrene
      analogues, in which the linear anthracene nucleus is replaced by the bent
      phenanthrene nucleus; and azaphenanthrenes. The tetrahydroazonafides were
      generally intermediate in potencies between amonafide and azonafide against the
      tumor cells, but some of them had high potencies against the L1210 cells and were
      more potent against the MDR strain than the sensitive strain. The phenanthrene
      and azaphenanthrene analogues showed no improvement on the potencies of the
      anthracenes.

PMID- 10956215
TI  - 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists.
AB  - Phenylalkylamines such as 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB;
      1a) and its corresponding iodo derivative DOI (2) are commonly used 5-HT(2)
      serotonin agonists. Previous studies have established that the 2,5-dimethoxy
      substitution pattern found in these compounds is optimal for high affinity at 5
      HT(2A) receptors and that substituents at the 4-position can modulate affinity
      over a wide range. We have previously shown, however, that when the 4-position is
      substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with
      an affinity comparable to that of 1a but that it possesses 5-HT(2A) antagonist
      character. The present study examined the structure-affinity relationships of 3,
      and the results were very much unexpected. That is, the 2,5-dimethoxy
      substitution pattern of 3 is not required for high affinity. Either of the two
      methoxy groups can be removed without untoward effect on affinity, and relocation
      of the methoxy substituents actually enhances affinity by as much as an order of
      magnitude. None of the compounds displayed more than 20-fold selectivity for 5
      HT(2A) over 5-HT(2C) receptors. In addition, several were demonstrated to act as
      5-HT(2A) partial agonists. As such, the results of this study suggest that the
      structure-affinity relationships of phenylalkylamines as 5-HT(2A) ligands now be
      reinvestigated in greater detail.

PMID- 10956216
TI  - Structure-function studies of polymyxin B nonapeptide: implications to
      sensitization of gram-negative bacteria.
AB  - Polymyxin B nonapeptide (PMBN), a cationic cyclic peptide derived by enzymatic
      processing from the naturally occurring peptide polymyxin B, is able to increase
      the permeability of the outer membrane of Gram-negative bacteria toward
      hydrophobic antibiotics probably by binding to the bacterial lipopolysaccharide
      (LPS). We have synthesized 11 cyclic analogues of PMBN and evaluated their
      activities compared to that of PMBN. The synthetic peptides were much less potent
      than PMBN in their capacity to sensitize Escherichia coli and Klebsiella
      pneumoniae toward novobiocin and to displace dansyl-PMBN from Escherichia coli
      LPS. Moreover, unlike PMBN, none of the analogues were able to inhibit the growth
      of Pseudomonas aeruginosa. The structural-functional features of PMBN were
      characterized and identified with regard to the ring size, the distance between
      positive charges and peptide backbone, the chirality of the DPhe-Leu domain, and
      the nature of the charged groups. Apparently, the structure of PMBN is highly
      specific for efficient perturbation of the outer membrane of Gram-negative
      bacteria as well as for LPS binding. The present study further increases our
      understanding of the complex PMBN-LPS and may, potentially, enable the design of
      compounds having enhanced permeabilization potency of the Gram-negative outer
      membrane.

PMID- 10956217
TI  - Synthesis and biological evaluation of 2'-carbamate-linked and 2'-carbonate
      linked prodrugs of paclitaxel: selective activation by the tumor-associated
      protease plasmin.
AB  - The nontoxic paclitaxel-2'-carbamate prodrugs 2-5 and paclitaxel-2'-carbonate
      prodrug 6 were synthesized and tested for activation by the tumor-associated
      enzyme plasmin. A generally applicable method for the synthesis of paclitaxel-2'
      carbamates was developed. In buffer solution, prodrug 2, which contained an
      unsubstituted ethylenediamine spacer, was not stable, whereas prodrugs 3-6 were
      highly stable. Prodrugs 3-6 showed on average a decrease in cytotoxicity of more
      than 8000-fold in comparison with the parent drug in seven human tumor cell
      lines. Prodrugs 5 and 6 are the most nontoxic prodrugs of paclitaxel that yield
      the free parent drug upon selective activation currently reported. Enzyme
      hydrolysis and spacer elimination rates were determined by incubation of prodrugs
      5 and 6 in the presence of human plasmin. From these results, prodrug 6 was
      selected as the promising prodrug for further in vivo studies.

PMID- 10956218
TI  - Novel radiotracers for imaging the serotonin transporter by positron emission
      tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of
      (11)C-labeled 2-(phenylthio)araalkylamines.
AB  - A series of four 2-(phenylthio)araalkylamines have been radiolabeled with (11)C
      and evaluated as potential radiotracers for imaging the serotonin transporter
      (SERT) by positron emission tomography (PET). All four candidates display high
      affinity for SERT and low affinity for the dopamine or norepinephrine
      transporters using in vitro binding assays. Biodistribution studies in rats
      demonstrated that tail-vein injection of the (11)C-labeled radiotracers resulted
      in high brain uptake of radioactivity with a preferential distribution in brain
      regions known to be rich in SERT such as hypothalamus and thalamus. The most
      promising candidate, 16, had hypothalamus-to-cerebellum ratios of 9:1, 1 h
      postinjection, an indication of high specific to nonspecific binding. Ex vivo
      pharmacological studies demonstrated that uptake in SERT-rich brain regions was
      both saturable and selective for SERT. Two of the tested radiotracers, 15 and 16,
      have highly favorable properties for imaging SERT and will be used in pilot human
      PET imaging studies.

PMID- 10956219
TI  - Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl
      biphenylsulfonamides as a new class of potent, highly selective ET(A)
      antagonists.
AB  - The synthesis and structure-activity relationship (SAR) studies of a series of 4'
      oxazolyl-N-(3,4-dimethyl-5-isoxazolyl)[1, 1'-biphenyl]-2-sulfonamide derivatives
      as endothelin-A (ET(A)) receptor antagonists are described. The data reveal a
      remarkable improvement in potency and metabolic stability when the 4'-position of
      the biphenylsulfonamide is substituted with an oxazole ring. Additional 2'
      substitution of an acylaminomethyl group further increased the binding activity
      and provided one of the first subnanomolar ET(A)-selective antagonists in the
      biphenylsulfonamide series (17, ET(A) K(i) = 0.2 nM). Among the compounds
      described, 3 (N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1, 1'-biphenyl]-2
      sulfonamide; BMS-193884) had the optimum pharmacological profile and was
      therefore selected as a clinical candidate for studies in congestive heart
      failure.

PMID- 10956220
TI  - Synthesis and structure-activity relationships of a new set of 2-arylpyrazolo[3,4
      c]quinoline derivatives as adenosine receptor antagonists.
AB  - In a recent paper (Colotta et al. J. Med. Chem. 2000, 43, 1158-1164) we reported
      the synthesis and adenosine receptor binding activity of two sets of 2-aryl-1,2,4
      triazolo[4,3-a]quinoxalines (A and B) some of which were potent and selective
      A(1) or A(3) antagonists. In this paper the synthesis of a set of 2
      arylpyrazolo[3,4-c]quinolin-4-ones 1-10, 4-amines 11-18, and 4-amino-substituted
      derivatives 19-35 are reported. The binding activity at bovine A(1) and A(2A) and
      human cloned A(3) adenosine receptors showed that (i) the substituent on the
      appended 2-phenyl ring could be used to modulate A(1) and A(3) affinity, (ii) the
      4-amino group was necessary for A(1) and A(2A) binding activity, and (iii) a
      nuclear or extranuclear C=O proton acceptor at position 4 yielded potent and
      selective A(3) antagonists. These results are in agreement with those of the
      previously reported series A and B suggesting a similar adenosine receptor
      binding mode. In particular, the A(3) nanomolar affinity of 1-8, 31-33, and 35
      confirms the hypothesis of the presence in the N-6 region of the adenosine A(3)
      subtype of a proton donor able to bind to a C=O proton acceptor at position 4.

PMID- 10956221
TI  - Effect of C9-methyl substitution and C8-C9 conformational restriction on
      antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3
      d]pyrimidines.
AB  - N-[4-[1-methyl-2-(2,4-diaminofuro[2, 3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic
      acid (5) and its C8-C9 conformationally restricted E- and Z-isomers (6 and 7)
      were designed and synthesized in order to investigate the effect of incorporating
      a methyl group at the C9 position and of conformational restriction at the C8-C9
      bridge of N-[4-[2-(2,4-diaminofuro[2, 3-d]pyrimidin-5-yl)ethyl]benzoyl]-L
      glutamic acid (1) with respect to dihydrofolate reductase (DHFR) inhibitory
      activity as well as antitumor activity. The compounds were synthesized by a
      Wittig reaction of 2,4-diamino-5-(chloromethyl)furo[2,3-d]pyrimidine with ethyl 4
      acetylbenzoate followed by catalytic reduction, hydrolysis, and standard peptide
      coupling with diethyl L-glutamate. The biological results indicated that the
      addition of a 9-methyl group to the C8-C9 bridge, as in 5, increased recombinant
      human (rh) DHFR inhibitory potency (IC(50) = 0.42 microM) as well as the potency
      against the growth inhibition of tumor cells in culture (CCRF-CEM EC(50) = 29 nM,
      A253 EC(50) = 28.5 nM, and FaDu EC(50) = 17.5 nM) compared with the 9-desmethyl
      analogue 1. However, the conformationally restricted 4:1 Z/E mixture of 7 and 6
      was less potent than 5 in both assays, and the pure E-isomer 6 was essentially
      inactive. These three classical analogues were also evaluated as inhibitors of
      Lactobacillus casei, Escherichia coli, and rat and rh thymidylate synthase (TS)
      and were found to be weak inhibitors. All three analogues 5-7 were good
      substrates for human folylpolyglutamate synthetase (FPGS). These data suggested
      that FPGS is relatively tolerant to different conformations in the bridge region.
      Further evaluation of the cytotoxicity of 5 and 7 in methotrexate (MTX)-resistant
      CCRF-CEM cell sublines suggested that polyglutamylation was crucial for their
      mechanism of action. Metabolite protection studies of 5 implicated DHFR as the
      primary intracellular target. Compound 5 showed GI(50) values in 10(-9)-10(-7) M
      range against more than 30 tumor cell lines in culture.

PMID- 10956222
TI  - Synthesis and structure-activity relationships of 7-substituted 3-(2, 6
      dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as selective inhibitors of pp60(c
      src).
AB  - 7-substituted 3-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-ones are potent
      inhibitors of protein tyrosine kinases, with some selectivity for c-Src. The
      compounds were prepared by condensing 4, 6-diaminonicotinaldehyde with 2,6
      dichlorophenylacetonitrile and selectively converting the 2- and 7-amino groups
      of the product to hydroxy and fluoro groups, respectively, by prolonged
      diazotization in 50% aqueous fluoboric acid. N-Methylation, followed by treatment
      with aliphatic diamines, aromatic amines, or their derived lithium anions, gave
      the desired compounds. Selected isomeric 1, 8-naphthyridin-2(1H)-ones were also
      prepared in order to evaluate the relative contributions of both ring A aza atoms
      of the related pyrido[2,3-d]pyrimidin-7(8H)-ones to the inhibitory activity. The
      compounds were evaluated for their ability to prevent phosphorylation of a model
      substrate by c-Src, FGF-1 receptor, and PDGF-beta receptor enzymes. Overall,
      there was a high degree of correlation of the activities against the different
      kinases, with c-Src being generally the most sensitive to structural changes. 1,
      6-Naphthyridin-2(1H)-one analogues bearing basic aliphatic side chains [7
      NH(CH(2))(n)()NRR, 7-NHPhO(CH(2))(n)()NRR, or 7-NHPhN(CH(2))(4)NMe] were the most
      potent against c-Src (IC(50)s of 10-80 nM), showing good selectivity with respect
      to PDGFR (10-300-fold) but less with respect to FGFR. The 1, 6-naphthyridin-2(1H)
      ones showed broadly similar activity to the analogous pyrido[2,3-d]pyrimidin
      7(8H)-ones, whereas the 1, 8-naphthyridin-2(1H)-ones were at least 10(3)-fold
      less potent. These results, indicating that the 3-aza atom in the pyrido[2, 3
      d]pyrimidin-7(8H)-ones is mandatory, whereas the 1-aza atom is not, support the
      published binding model for these compounds to c-Src (J. Med. Chem. 1998, 41,
      1752), where the 3-aza and 2-NH atoms form a bidentate H-bond donor-acceptor
      motif that interacts with Met341 and the 1-aza atom is not involved in specific
      binding interactions.

PMID- 10956223
TI  - Use of an additional hydrophobic binding site, the Z site, in the rational drug
      design of a new class of stronger trypanothione reductase inhibitor, quaternary
      alkylammonium phenothiazines.
AB  - Improved rationally designed lead drug structures against African
      trypanosomiasis, Chagas disease, and leishmaniasis were obtained against
      trypanothione reductase from Trypanosoma cruzi. Substituted-benzyl [3-(2-chloro
      4a, 10a-dihydrophenothiazin-10-yl)propyl]dimethylammonium salts, synthesized by
      Menschutkin quaternization of the tertiary alkylamine omega-nitrogen atom of
      chlorpromazine, were linear, competitive inhibitors of recombinant trypanothione
      reductase from T. cruzi, with either trypanothione disulfide or N
      benzyloxycarbonyl-L-cysteinylglycyl 3-dimethylaminopropylamide disulfide as
      substrate. The permanent positive charge on the distal nitrogen atom of the
      tricyclic side chain contribution to binding was estimated as >/=5.6 kcal.mol(-1)
      by comparison with the analogue with the cationic nitrogen atom of the quaternary
      replaced by an ether oxygen atom. A further major contribution to improving K(i)
      values and inhibition strength was the hydrophobic natures and structures of the
      N-benzyl substituents. The strongest inhibitor, the [3-(2-chloro-4a,10a
      dihydrophenothiazin-10-yl)propyl](3, 4-dichlorobenzyl)dimethylammonium derivative
      (K(i) 0.12 microM), was approximately 2 orders of magnitude more inhibitory than
      the parent chlorpromazine. Several of these quaternary phenothiazines completely
      inhibited T. brucei parasite growth in vitro at <1 microM. Antiparasite activity
      was not solely determined by inhibition strength against trypanothione reductase,
      there being a strong contribution from hydrophobicity (for example, benzhydryl
      quaternized chlorpromazime had ED(50) < 1 microM). Although active against
      Leishmania donovani, none of the analogues showed major improvement in this
      activity relative to chlorpromazine or other nonquaternized phenothiazines. The p
      tert-butylbenzyl-quaternized analogue very strongly inhibited (ED(50) < 1 microM)
      growth of the amastigote stage of T. cruzi.

PMID- 10956224
TI  - Development of novel quinone phosphorodiamidate prodrugs targeted to DT
      diaphorase.
AB  - A series of naphthoquinone and benzimidazolequinone phosphorodiamidates has been
      synthesized and studied as potential cytotoxic prodrugs activated by DT
      diaphorase. Reduction of the quinone moiety in the target compounds was expected
      to provide a pathway for expulsion of the phosphoramide mustard alkylating agent.
      All of the compounds synthesized were excellent substrates for purified human DT
      diaphorase (k(cat)/K(m) = 3 x 10(7) - 3 x 10(8) M(-1) s(-1)). The naphthoquinones
      were toxic to both HT-29 and BE human colon cancer cell lines in a clonogenic
      assay; however, cytotoxicity did not correlate with DT-diaphorase activity in
      these cell lines. The benzimidazolequinone analogues were 1-2 orders of magnitude
      less cytotoxic than the naphthoquinone analogues. Chemical reduction of the
      naphthoquinone led to rapid expulsion of the phosphorodiamidate anion; in
      contrast, the benzimidazole reduction product was stable. Michael addition of
      glutathione and other sulfur nucleophiles provides an alternate mechanism for
      activation of the naphthoquinone phosphorodiamidates, and this mechanism may
      contribute to the cytotoxicity of these compounds.

PMID- 10956225
TI  - Selective cyclooxygenase-2 inhibitors: heteroaryl modified 1,2-diarylimidazoles
      are potent, orally active antiinflammatory agents.
AB  - A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and
      found to be potent and highly selective (1000-9000-fold) inhibitors of the human
      COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent
      activity in acute (carrageenan induced paw edema, ED(50) = 5.4 mg/kg) and chronic
      (adjuvant induced arthritis, ED(50) = 0.25 mg/kg) models of inflammation. The
      relatively long half-life of 25 in rat and dog prompted investigation of the
      pyridyl and other heteroaromatic systems containing potential metabolic
      functionalities. A number of substituted pyridyl and thiazole containing
      compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in
      every efficacy model evaluated. Several orally active diarylimidazoles exhibited
      desirable pharmacokinetics profiles and showed no GI toxicity in the rat up to
      100 mg/kg in both acute and chronic models. The paper describes facile and
      practical syntheses of the targeted diarylimidazoles. The structure-activity
      relationships and antiinflammatory properties of a series of diarylimidazoles are
      discussed.

PMID- 10956226
TI  - Highly stable C(60)/poly(vinylpyrrolidone) charge-transfer complexes afford new
      predictions for biological applications of underivatized fullerenes.
AB  - The equilibrium constants for complexation of C(60) with poly(vinylpyrrolidone)
      (PVP) in water have been determined by UV-visible spectroscopy. The magnitude of
      the equilibrium constants was found to describe the formation of a charge
      transfer (CT) saturated 1:1 complex for [PVP] = 2.62-5.25 x 10(-2) M (K = 1331.3
      M(-1)), and a contact-pairs complex for [PVP] = 7.0-12.25 x 10(-2) M (K = 20.64 x
      10(-2) M(-1)). These results indicate that the binding affinity of C(60) for drug
      receptors, base pairs in double-stranded DNA, or AT-rich segments of its minor
      groove to form CT complexes is limited by the strong coordination in the
      C(60)/PVP-saturated CT complex or envelopment by the polymer ligand in the
      contact CT complex.

PMID- 10956227
TI  - Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum
      complexes: comparison of effects of geometry and polyfunctionality on biological
      activity.
AB  - The synthesis of two new isomeric trifunctional dinuclear platinum complexes of
      formula [?PtCl(NH(3))(2)?micro-NH(2)(CH(2))(6)NH(2)-?PtCl(2)(N H(3))?](+) (1,
      2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor
      cell lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH(3))(2)Cl(2)])
      is described and compared with the profile for their bifunctional analogues,
      [?cis/trans-PtCl(NH(3))(2)?(2)micro-NH(2)(CH(2))(6)NH(2)](2+ ). The trifunctional
      dinuclear platinum complexes showed a unique profile of cytotoxicity against
      human cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell
      lines. The resistance factor is dependent on the geometry of the Pt coordination
      spheres - suggesting that these may be associated with DNA-binding modes.
      Retention of activity against CDDP-resistant cell lines and a different spectrum
      of activity compared to CDDP and also within different classes of polynuclear
      platinum complexes suggest that not only are they mechanistically different from
      mononuclear platinum complexes but also each individual class of polynuclear
      platinum structure may have its own unique character.

PMID- 10956228
TI  - Probes for narcotic receptor-mediated phenomena. 27. Synthesis and
      pharmacological evaluation of selective delta-opioid receptor agonists from 4
      [(alphaR)-alpha-(2S,5R)-4-substituted-2, 5-dimethyl-1-piperazinyl-3
      methoxybenzyl]-N,N-diethylbenzamides and their enantiomers.
AB  - Potent, selective, and efficacious delta-opioid receptor agonists such as (+)-4
      [(alphaR)-alpha-(2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl-3-methoxybenzyl]-N,N
      diethylbenzamide [SNC80, (+)-2] have been found to be useful tools for exploring
      the structural requirements which are necessary for ligands which interact with
      the delta-receptor. To determine the necessity for the 4-allyl moiety in (+)-2,
      this substituent was replaced with a variety of 4-alkyl, 4-arylalkyl, and 4
      alkenyl substituents. The corresponding enantiomers of these compounds were also
      synthesized. The binding affinities for the mu-, delta-, and kappa-opioid
      receptors and efficacies in the functional GTPgammaS binding assay were
      determined for the (+)-2 related compounds and their enantiomers. The 4-crotyl
      analogue was found to have similar delta-receptor affinity and efficacy as (+)-2,
      but the 4-cyclopropylmethyl analogue, in the functional assay, appeared to be a
      partial agonist with little antagonist activity.

PMID- 10956229
TI  - New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF
      receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis

PMID- 10956230
TI  - Pavlov and integrative physiology.
AB  - Ivan Petrovich Pavlov was the first physiologist to win the Nobel Prize. The
      Prize was given in 1904 for his research on the neural control of salivary,
      gastric, and pancreatic secretion. A major reason for the success and novelty of
      his research was the use of unanesthetized dogs surgically prepared with chronic
      fistulas or gastric pouches that permitted repeated experiments in the same
      animal for months. Pavlov invented this chronic method because of the limitations
      he perceived in the use of acute anesthetized animals for investigating
      physiological systems. By introducing the chronic method and by showing its
      experimental advantages, Pavlov founded modern integrative physiology. This paper
      reviews Pavlov's journey from his birthplace in a provincial village in Russia to
      Stockholm to receive the Prize. It begins with childhood influences, describes
      his training and mentors, summarizes the major points of his research by
      reviewing his book Lectures on the Work of the Digestive Glands, and discusses
      his views on the relationship between physiology and medicine.

PMID- 10956231
TI  - Water ingestion provides an early signal inhibiting osmotically stimulated
      vasopressin secretion in rats.
AB  - Dehydrated dogs are known to inhibit secretion of vasopressin (VP) within minutes
      after drinking water, before plasma osmolality (P(osmol)) diminishes. The present
      studies determined whether water ingestion causes a similar rapid inhibition of
      neurohypophyseal hormone secretion in rats. Adult rats were infused with 1 M NaCl
      (2 ml/h iv) for 240 min to stimulate VP and oxytocin (OT) secretion. After 220
      min of infusion, rats were given water to drink for 5 min, and blood samples were
      taken 5 and 15 min later for RIA. Plasma VP (pVP) was much lower when rats
      ingested water than when they drank nothing even though P(osmol) was not
      significantly altered. Plasma OT (pOT) was affected similarly. In contrast, no
      effects on pVP or pOT occurred when rats drank isotonic NaCl solution for 5 min
      in amounts comparable to the water intakes (approximately 5.5 ml). These results
      suggest that neurohypophyseal secretion of VP and OT in rats is inhibited rapidly
      by water drinking, and that this inhibition is mediated by a visceral signal of
      osmotic dilution rather than by the act of drinking per se.

PMID- 10956232
TI  - Nonlinear response of the immune system to power-frequency magnetic fields.
AB  - Studies of the effects of power-frequency electromagnetic fields (EMFs) on the
      immune and other body systems produced positive and negative results, and this
      pattern was usually interpreted to indicate the absence of real effects. However,
      if the biological effects of EMFs were governed by nonlinear laws, deterministic
      responses to fields could occur that were both real and inconsistent, thereby
      leading to both types of results. The hypothesis of real inconsistent effects due
      to EMFs was tested by exposing mice to 1 G, 60 Hz for 1-105 days and observing
      the effect on 20 immune parameters, using flow cytometry and functional assays.
      The data were evaluated by means of a novel statistical procedure that avoided
      averaging away oppositely directed changes in different animals, which we
      perceived to be the problem in some of the earlier EMF studies. The reliability
      of the procedure was shown using appropriate controls. In three independent
      experiments involving exposure for 21 or more days, the field altered lymphoid
      phenotype even though the changes in individual immune parameters were
      inconsistent. When the data were evaluated using traditional linear statistical
      methods, no significant difference in any immune parameter was found. We were
      able to mimic the results by sampling from known chaotic systems, suggesting that
      deterministic chaos could explain the effect of fields on the immune system. We
      conclude that exposure to power-frequency fields produced changes in the immune
      system that were both real and inconsistent.

PMID- 10956233
TI  - alpha(2)-adrenergic receptor-mediated increase in NO production buffers renal
      medullary vasoconstriction.
AB  - The present study was designed to investigate the role of nitric oxide (NO) in
      modulating the adrenergic vasoconstrictor response of the renal medullary
      circulation. In anesthetized rats, intravenous infusion of norepinephrine (NE) at
      a subpressor dose of 0.1 microgram. kg(-1). min(-1) did not alter renal cortical
      (CBF) and medullary (MBF) blood flows measured by laser-Doppler flowmetry nor
      medullary tissue PO(2) (P(m)O(2)) as measured by a polarographic microelectrode.
      In the presence of the NO synthase inhibitor nitro-L-arginine methyl ester (L
      NAME) in the renal medulla, intravenous infusion of NE significantly reduced MBF
      by 30% and P(m)O(2) by 37%. With the use of an in vivo microdialysis
      oxyhemoglobin NO-trapping technique, we found that intravenous infusion of NE
      increased interstitial NO concentrations by 43% in the renal medulla. NE
      stimulated elevations of tissue NO were completely blocked either by renal
      medullary interstitial infusion of L-NAME or the alpha(2)-antagonist rauwolscine
      (30 microgram. kg(-1). min(-1)). Concurrently, intavenous infusion of NE resulted
      in a significant reduction of MBF in the presence of rauwolscine. The alpha(1)
      antagonist prazosin (10 microgram. kg(-1). min(-1) renal medullary interstitial
      infusion) did not reduce the NE-induced increase in NO production, and NE
      increased MBF in the presence of prazosin. Microdissection and RT-PCR analyses
      demonstrated that the vasa recta expressed the mRNA of alpha(2B)-adrenergic
      receptors and that medullary thick ascending limb and collecting duct expressed
      the mRNA of both alpha(2A)- and alpha(2B)-adrenergic receptors. These subtypes of
      alpha(2)-adrenergic receptors may mediate NE-induced NO production in the renal
      medulla. We conclude that the increase in medullary NO production associated with
      the activation of alpha(2)-adrenergic receptors counteracts the vasoconstrictor
      effects of NE in the renal medulla and may play an important role in maintaining
      a constancy of MBF and medullary oxygenation.

PMID- 10956234
TI  - Water stimulation of the posterior oral cavity induces inhibition of gastric
      motility.
AB  - The response of gastric motility to the administration of water and saline in the
      larynx and epiglottis was investigated in urethan-chloralose anesthetized rats.
      Administration of water inhibited motility of the distal stomach, but 0.15 M NaCl
      did not induce the inhibitory response. Bilateral sectioning of the superior
      laryngeal nerve (SLN) abolished the inhibitory response induced by water.
      Bilateral cervical vagotomies abolished the inhibitory responses, although spinal
      transection did not affect the inhibitory response. These inhibitory responses
      have been observed in immobilized animals. The degree of inhibition by water and
      hypotonic saline was negatively correlated with the sodium concentration. In
      contrast, the degree of inhibition to hypertonic saline was positively correlated
      with the sodium concentration. The proximal stomach also showed a reduction in
      intragastric pressure in response to the administration of water. These findings
      suggest that water-responsive afferent neurons in the SLN suppress gastric
      motility via the vagal efferent nerve.

PMID- 10956235
TI  - Interleukin-13 and transforming growth factor-beta1 inhibit spontaneous sleep in
      rabbits.
AB  - Proinflammatory cytokines, including interleukin-1beta and tumor necrosis factor
      alpha are involved in physiological sleep regulation. Interleukin (IL)-13 and
      transforming growth factor (TGF)-beta1 are anti-inflammatory cytokines that
      inhibit proinflammatory cytokines by several mechanisms. Therefore, we
      hypothesized that IL-13 and TGF-beta1 could attenuate sleep in rabbits. Three
      doses of IL-13 (8, 40, and 200 ng) and TGF-beta1 (40, 100, and 200 ng) were
      injected intracerebroventricularly 3 h after the beginning of the light period.
      In addition, one dose of IL-13 (200 ng) and one dose of TGF-beta1 (200 ng) were
      injected at dark onset. The two higher doses of IL-13 and the highest dose of TGF
      beta1 significantly inhibited spontanenous non-rapid eye movement sleep (NREMS)
      when they were given in the light period. IL-13 also inhibited NREMS after dark
      onset administration; however, the inhibitory effect was less potent than that
      observed after light period administration. The 40-ng dose of IL-13 inhibited
      REMS duration during the dark period. TGF-beta1 administered at dark onset had no
      effect on sleep. These data provide additional evidence for the hypothesis that a
      brain cytokine network is involved in regulation of physiological sleep.

PMID- 10956236
TI  - IL-1 is a mediator of increases in slow-wave sleep induced by CRH receptor
      blockade.
AB  - We hypothesize that corticotropin-releasing hormone (CRH), a regulator of the
      hypothalamic-pituitary-adrenal (HPA) axis, is involved in sleep-wake regulation
      on the basis of observations that the CRH receptor antagonist astressin, after a
      delay of several hours, reduces waking and increases slow-wave sleep (SWS) in
      rats. This delay suggests a cascade of events that begins with the HPA axis and
      culminates with actions on sleep regulatory systems in the central nervous
      system. One candidate mediator in the brain for these actions is interleukin (IL)
      1. IL-1 promotes sleep, and glucocorticoids inhibit IL-1 synthesis. In this
      study, central administration of 12.5 microgram astressin into rats before dark
      onset reduced corticosterone 4 h after injection and increased mRNA expression
      for IL-1alpha and IL-1beta but not for IL-6 or tumor necrosis factor-alpha in the
      brain 6 h after injection. To determine directly whether IL-1 is involved in
      astressin-induced alterations in sleep-wake behavior, we then pretreated rats
      with 20 microgram anti-IL-1beta antibodies before injecting astressin. The
      increase in SWS and the reduction in waking that occur after astressin are
      abolished when animals are pretreated with anti-IL-1beta. These data indicate
      that IL-1 is a mediator of astressin-induced alterations in sleep-wake behavior.

PMID- 10956237
TI  - UTP binding and phosphoinositidase C activation in ampulla from frog semicircular
      canal.
AB  - Pyrimidine nucleotide-sensitive phosphoinositidase C activity (PLC), previously
      identified in frog semicircular canal ampulla, was pharmacologically
      characterized. Binding of [(3)H]UTP and abilities of unlabeled nucleotide analogs
      to inhibit binding and to stimulate PLC in myo-[(3)H]inositol-loaded ampullas
      were determined. Specific [(3)H]UTP binding was competitively inhibited by UTP
      [apparent dissociation binding constant = 0.8 microM; Hill coefficient = 0.7].
      Scatchard analysis revealed a minor class of high-affinity binding sites [45 fmol
      UTP bound/microgram protein; dissociation constant (K(D1)) = 0.4 microM] and a
      major class of moderate-affinity binding sites (365 fmol UTP bound/microgram
      protein; K(D2) = 10 microM). The stereospecificity pattern for UTP analog
      recognition was UMP > UDP >/= ADP = UTP = dTTP > adenosine 5'-O-(3
      thiotriphosphate) = ATP = CTP = 2'-and 3'-O-4-(benzoylbenzoyl)-ATP (Bz-ATP) >/=
      AMP >/= 2-methylthio-ATP = alpha,beta-methylene-ATP > uridine = diadenosine
      tetraphosphate (Ap(4)A); cAMP and adenosine were inactive. Antagonist recognition
      pattern was DIDS = pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS)
      = reactive blue 2 > suramin. The rank order of potencies for agonist-induced PLC
      activation was UDP >/= UTP >/= Ap(4)A >/= UMP = Bz-ATP; uridine was inactive. UTP
      stimulated PLC activity was inhibited by DIDS = reactive blue 2 = PPADS >
      suramin. These results suggest that the population of [(3)H]UTP-labeled binding
      sites is heterogeneous, with a low number of high-affinity UTP receptors whose
      function(s) need to be determined and a large number of moderate-affinity
      receptors triggering PLC activation.

PMID- 10956238
TI  - Behavioral feedback regulation of circadian rhythm phase angle in light-dark
      entrained mice.
AB  - Induced and spontaneous wheel running can alter the phase and period (tau) of
      circadian rhythms in rodents. The relationship between spontaneous running and
      the phase angle (psi) of entrainment to 24-h light-dark (LD) cycles was evaluated
      in C57BL/6j mice. With a wheel freely available, psi was significantly correlated
      with the absolute (r = 0.32) and relative (r = 0.44) amount of activity during
      the first 2 h of the activity period. When wheels were locked during the first
      half of the night in LD and then unlocked in constant dark (DD), mice exhibited a
      delayed psi and lengthened tau compared with mice that had wheels locked during
      the second half of the night. In DD, tau correlated negatively with total daily
      activity. To evaluate if wheel running modulates the phase-resetting actions of
      LD, phase shifts to light pulses were measured at two time points in DD, when
      daily activity levels differed by 40%. Phase delays to light were 56% greater
      when activity levels were lower. However, in a counterbalanced follow-up
      experiment, phase advances and delays to light pulses were not affected by the
      availability of wheels, although an effect of time in DD was replicated.
      Spontaneous activity can regulate psi and tau without altering the response of
      the pacemaker to light.

PMID- 10956239
TI  - Low LBNP tolerance in men is associated with attenuated activation of the renin
      angiotensin system.
AB  - Plasma vasoactive hormone concentrations [epinephrine (p(Epi)), norepinephrine
      (p(NE)), ANG II (p(ANG II)), vasopressin (p(VP)), endothelin-1 (p(ET-1))] and
      plasma renin activity (p(RA)) were measured periodically and compared during
      lower body negative pressure (LBNP) to test the hypothesis that responsiveness of
      the renin-angiotensin system, the latter being one of the most powerful
      vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy
      men on a controlled diet (2,822 cal/day, 2 mmol. kg(-1). day(-1) Na(+)) were
      exposed to 30 min of LBNP from -15 to -50 mmHg. LBNP was uneventful for seven men
      [25 +/- 2 yr, high-tolerance (HiTol) group], but eight men (26 +/- 3 yr) reached
      presyncope after 11 +/- 1 min [P < 0.001, low-tolerance (LoTol) group]. Mean
      arterial pressure (MAP) did not change measurably, but central venous pressure
      and left atrial diameter decreased similarly in both groups (5-6 mmHg, by
      approximately 30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were
      similar between groups, however, p(RA) differed between them (LoTol 0.6 +/- 0.1,
      HiTol 1.2 +/- 0.1 ng ANG I. ml(-1). h(-1), P < 0.05). LBNP increased (P < 0. 05)
      p(RA) and p(ANG II), respectively, more in the HiTol group (9.9 +/- 2.2 ng ANG I.
      ml(-1). h(-1) and 58 +/- 12 pg/ml) than in LoTol subjects (4.3 +/- 0.9 ng ANG I.
      ml(-1). h(-1) and 28 +/- 6 pg/ml). In contrast, the increase in p(VP) was higher
      (P < 0.05) in the LoTol than in the HiTol group. The increases (P < 0.05) for
      p(NE) were nonsignificant between groups, and p(ET-1) remained unchanged. Thus
      there may be a causal relationship between attenuated activation of p(RA) and
      p(ANG II) and presyncope, with p(VP) being a possible cofactor. Measurement of
      resting p(RA) may be of predictive value for those with lower hypotensive
      tolerance.

PMID- 10956240
TI  - Antenatal glucocorticoids alter premature newborn lamb neuroendocrine and
      endocrine responses to hypoxia.
AB  - Glucocorticoids are administered for preterm labor to improve postnatal
      adaptation. We assessed the effect of antenatal betamethasone (Beta) treatment on
      preterm newborn lamb neuroendocrine [catecholamine, arginine vasopressin (AVP)]
      and endocrine [triiodothyronine (T(3)), ANG II, and atrial natriuretic factor
      (ANF)] adaptive responses following delivery and a hypoxic challenge. Beta
      treatment included direct fetal injection at 0.2 (F(0.2); n = 8) or 0.5 (F(0.5);
      n = 7) mg/kg estimated fetal body weight or maternal injection with 0.2 (n = 8)
      or 0.5 mg/kg (M(0.5); n = 8). Control animals received fetal and maternal
      intramuscular injections of saline (n = 8). After 24 h, lambs were delivered by
      cesarean section, surfactant treated, and ventilated for 4 h. Relative to the
      control lambs, 3 h after delivery, there was a marked suppression of plasma
      cortisol, epinephrine, norepinephrine, and ANG II levels and elevated plasma T(3)
      and ANF levels, systolic blood pressure, and left ventricular contractility
      (dP/dt; F(0.5) and M(0.5)) values in F(0.5) and both maternal Beta-treated
      groups. However, Beta treatment augmented the cardiac output, cortisol,
      norepinephrine, AVP, and ANF responses to 20 min of hypoxia (PO(2) = 25-30 mmHg).
      We concluded that short-term (24 h) antenatal glucocorticoid exposure 1) alters
      preterm newborn postnatal blood pressure regulation in the face of marked
      depression of plasma cortisol, catecholamine, and ANG II levels and 2) augments
      the postnatal neuroendocrine and endocrine responses to a hypoxic challenge.

PMID- 10956242
TI  - Regulation of uterine and umbilical amino acid uptakes by maternal amino acid
      concentrations.
AB  - We tested the hypothesis that decreased fetal amino acid (AA) supply, produced by
      maternal hypoaminoacidemia (low AA) during hyperglycemia (HG), is reversible with
      maternal AA infusion and regulates fetal insulin concentration ([I]). We measured
      net uterine and umbilical AA uptakes during maternal HG/low AA concentration
      ([AA]) and after maternal intravenous infusion of a mixed AA solution. After 5
      days HG, all maternal [AA] except glycine were decreased >50%, particularly
      essential [AA] (P < 0.00005). Most fetal [AA] also were decreased, especially
      branched-chain AA (P < 0.001). Maternal AA infusion increased net uterine uptakes
      of Val, Leu, Ile, Met, and Ser and net umbilical uptakes of Val, Leu, Ile, Met,
      Phe, and Arg but did not change net uteroplacental uptake of any AA. Fetal [I]
      increased 55 +/- 14%, P < 0.001, with correction of fetal [AA], despite the lack
      of change in fetal glucose concentration. Thus generalized maternal
      hypoaminoacidemia decreases uterine and umbilical uptakes of primarily the
      essential AA and decreases fetal branched-chain [AA]. These changes are reversed
      with correction of maternal [AA], which also increases fetal [I].

PMID- 10956241
TI  - Influence of hormone replacement therapy and aspirin on temperature regulation in
      postmenopausal women.
AB  - Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body
      temperature (T(b)) at a lower level than women not receiving hormone replacement
      therapy (untreated) and women using estrogen plus progesterone therapy (E + P),
      but it is not clear if reproductive hormones alter T(b) by directly acting on
      central thermoregulatory centers or indirectly via a secondary mediator(s). The
      purpose of the present investigation was to examine the possible involvement of
      pyrogenic cytokines and cyclooxygenase (COX) products (e.g., prostaglandins) in
      the regulation of T(b) in three groups of postmenopausal women (8 ERT, 7 E + P,
      and 8 untreated). We measured ex vivo secretion of cytokine agonists [tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta and -6] and modifiers (IL
      2 soluble receptor, IL-1 receptor antagonist, soluble TNF receptor type I,
      soluble TNF receptor type II, soluble IL-6 receptor, and soluble glycoprotein
      130) from peripheral blood mononuclear cells and thermoregulatory responses at
      rest and during 1 h of passive whole body heating in the postmenopausal women
      before and after 3 days of placebo or aspirin (50 mg. day(-1). kg(-1)). With and
      without aspirin, the ERT group had a lower baseline rectal temperature (T(re);
      0.44 degrees C, P < 0.004) and a reduced T(b) threshold for cutaneous
      vasodilation (0.29 degrees C and 0.38 degrees C, P < 0.01) compared with the
      untreated and E + P groups, respectively. In the placebo condition, waking
      morning oral temperature (T(or)) correlated with ex vivo secretion of the
      proteins associated with IL-6 bioactivity. Aspirin caused significant reductions
      in waking T(or) in the E + P group and in baseline T(re) in the untreated group.
      However, the difference in thermoregulation brought about by steroid hormone
      treatment could not be explained by these relatively modest apparent influences
      by cytokines and COX products. Therefore, the altered thermoregulation induced by
      reproductive steroid therapy appears to occur via a mechanism distinct from a
      classic infection-induced fever.

PMID- 10956243
TI  - Cerebral artery sarcoplasmic reticulum Ca(2+) stores and contractility: changes
      with development.
AB  - To test the hypothesis that sarcoplasmic reticulum (SR) Ca(2+) stores play a key
      role in norepinephrine (NE)-induced contraction of fetal and adult cerebral
      arteries and that Ca(2+) stores change with development, we performed the
      following study. In main branch middle cerebral arteries (MCA) from near-term
      fetal ( approximately 140 days) and nonpregnant adult sheep, we measured NE
      induced contraction and intracellular Ca(2+) concentration ([Ca(2+)](i)) in the
      absence and presence of different blockers. In adult MCA, after thapsigargin (10(
      6) M), the NE-induced responses of tension and [Ca(2+)](i) were 37 +/- 5 and 47
      +/- 7%, respectively, of control values (P < 0.01 for each). In the fetal artery,
      in contrast, this treatment resulted in no significant changes from control. When
      this was repeated in the absence of extracellular Ca(2+), adult MCA increases in
      tension and [Ca(2+)](i) were 32 +/- 5 and 13 +/- 3%, respectively, of control.
      Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN,
      3 x 10(-6) to 10(-5) M) resulted in increases in tension and [Ca(2+)](i) in both
      fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA,
      the increased tension and [Ca(2+)](i) responses to RYN were essentially
      eliminated in the presence of zero extracellular Ca(2+). These findings provide
      evidence that in fetal MCA, in contrast to those in the adult, SR Ca(2+) stores
      are of less importance in NE-induced contraction, with such contraction being
      almost wholly dependent on Ca(2+) flux via plasma membrane L-type Ca(2+)
      channels. In addition, they suggest that in both adult and fetal MCA, the RYN
      receptor is coupled to the plasma membrane Ca(2+)-activated K(+) channel and/or L
      type Ca(2+) channel.

PMID- 10956244
TI  - Adaptation of the 24-h growth hormone profile to a state of sleep debt.
AB  - In normal men, the majority of GH secretion occurs in a single large postsleep
      onset pulse that is suppressed during total sleep deprivation. We examined the
      impact of semichronic partial sleep loss, a highly prevalent condition, on the 24
      h growth hormone profile. Eleven young men were studied after six nights of
      restricted bedtimes (0100-0500) and after 7 nights of extended bedtimes (2100
      0900). Slow-wave sleep (SWS) was estimated as the duration of stages III and IV.
      Slow-wave activity (SWA) was calculated as electroencephalogram power density in
      the 0.5- to 3-Hz frequency range. During the state of sleep debt, the GH
      secretory pattern was biphasic, with both a presleep onset "circadian" pulse and
      a postsleep onset pulse. Postsleep onset GH secretion was negatively related to
      presleep onset secretion and tended to be positively correlated with the amount
      of concomitant SWA. When sleep was restricted, both SWS and SWA were increased
      during early sleep. Unexpectedly, the increase in SWA affected the second, rather
      than the first, SWA cycle, suggesting that presleep onset GH secretion may have
      limited SWA in the first cycle, possibly via an inhibition of central GH
      releasing hormone activity. Thus neither the GH profile nor the distribution of
      SWA conformed with predictions from acute sleep deprivation studies, indicating
      that adaptation mechanisms are operative during chronic partial sleep loss.

PMID- 10956245
TI  - Afferent pathways in cardiovascular adjustments induced by volume expansion in
      anesthetized rats.
AB  - The role of baroreceptors, cardiopulmonary receptors, and renal nerves in the
      cardiovascular adjustments to volume expansion (VE) with 4% Ficoll (Pharmacia; 1%
      body wt, 0.4 ml/min) were studied in urethan-anesthetized rats. In control
      animals, VE produced a transitory increase in mean arterial pressure (MAP), which
      peaked at 10 min (17 +/- 4 mmHg) and increases in renal (128 +/- 6 and 169 +/-
      19% of baseline at 10 and 40 min, respectively) and hindlimb vascular conductance
      (143 +/- 6 and 150 +/- 10%). These cardiovascular adjustments to VE were
      unaffected by bilateral vagotomy. After sinoaortic denervation, the increase in
      MAP induced by VE was greater than in control rats (30 +/- 4 mmHg). However,
      renal vasodilation in response to VE was blocked, whereas hindlimb vasodilation
      was similar to that observed in control rats. After unilateral renal denervation
      (ipsilateral to flow recording), the initial renal vasodilation was blocked.
      However, 40 min after VE, a significant renal vasodilation (125 +/- 4%) appeared.
      The hindlimb vasodilation and MAP responses were unaffected by renal denervation.
      These results demonstrate that the baroreceptor afferents are an essential
      component of cardiovascular adjustments to VE, especially in the control of renal
      vascular conductance. They also suggest that renal vasodilation induced by VE is
      mediated by neural and hormonal mechanisms.

PMID- 10956246
TI  - Leptin responses to physical inactivity induced by simulated weightlessness.
AB  - Physical inactivity induced by head-down bed rest (HDBR) affects body composition
      (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We
      investigated whether leptin and counterregulatory hormone levels are affected by
      a 7-day HDBR. Fasting blood was sampled daily (0700) in males (n = 8) and on
      alternating days in females (n = 8) for measurements of leptin, insulin,
      norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol,
      nonesterified fatty acid (NEFA), and glucose. BC was measured by H(2)(18)O
      dilution. Energy intake (men 10.5 +/- 0.2 MJ/day, women 7.9 +/- 0.3 MJ/day) and
      BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women
      20%, P = 0. 050), insulin (men 34%, P = 0.018; women 25%, P = 0.022), and the
      insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted.
      GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but
      glucose decreased only in women. In conclusion, HDBR increased leptin levels
      independently of stress response, changes in fat mass, energy intake, or gender.
      These changes were correlated to the insulin-resistance development in men.
      Further analyses are required, but the results have to be considered for longer
      HDBR periods with 1) the well-described drop in energy intake and 2) the BC
      changes.

PMID- 10956247
TI  - Muscle oxygen kinetics at onset of intense dynamic exercise in humans.
AB  - The present study examined the onset and the rate of rise of muscle oxidation
      during intense exercise in humans and whether oxygen availability limits muscle
      oxygen uptake in the initial phase of intense exercise. Six subjects performed 3
      min of intense one-legged knee-extensor exercise [65.3 +/- 3.7 (means +/- SE) W].
      The femoral arteriovenous blood mean transit time (MTT) and time from femoral
      artery to muscle microcirculation was determined to allow for an examination of
      the oxygen uptake at capillary level. MTT was 15.3 +/- 1.8 s immediately before
      exercise, 10.4 +/- 0.7 s after 6 s of exercise, and 4.7 +/- 0.5 s at the end of
      exercise. Arterial venous O(2) difference (a-v(diff) O(2)) of 18 +/- 5 ml/l
      before the exercise was unchanged after 2 s, but it increased (P < 0.05) after 6
      s of exercise to 43 +/- 10 ml/l and reached 146 +/- 4 ml/l at the end of
      exercise. Thigh oxygen uptake increased (P < 0.05) from 32 +/- 8 to 102 +/- 28
      ml/min after 6 s of exercise and to 789 +/- 88 ml/min at the end of exercise. The
      time to reach half-peak a-v(diff) O(2) and thigh oxygen uptake was 13 +/- 2 and
      25 +/- 3 s, respectively. The difference between thigh oxygen delivery (blood
      flow x arterial oxygen content) and thigh oxygen uptake increased (P < 0.05)
      after 6 s and returned to preexercise level after 14 s. The present data suggest
      that, at the onset of exercise, oxygen uptake of the exercising muscles increases
      after a delay of only a few seconds, and oxygen extraction peaks after
      approximately 50 s of exercise. The limited oxygen utilization in the initial
      phase of intense exercise is not caused by insufficient oxygen availability.

PMID- 10956248
TI  - Differential neural control of intrarenal blood flow.
AB  - To test whether renal sympathetic nerve activity (RSNA) can differentially
      regulate blood flow in the renal medulla (MBF) and cortex (CBF) of pentobarbital
      sodium-anesthetized rabbits, we electrically stimulated the renal nerves while
      recording total renal blood flow (RBF), CBF, and MBF. Three stimulation sequences
      were applied 1) varying amplitude (0.5-8 V), 2) varying frequency (0.5-8 Hz), and
      3) a modulated sinusoidal pattern of varying frequency (0. 04-0.72 Hz).
      Increasing amplitude or frequency of stimulation progressively decreased all flow
      variables. RBF and CBF responded similarly, but MBF responded less. For example,
      0.5-V stimulation decreased CBF by 20 +/- 9%, but MBF fell by only 4 +/- 6%. The
      amplitude of oscillations in all flow variables was progressively reduced as the
      frequency of sinusoidal stimulation was increased. An increased amplitude of
      oscillation was observed at 0.12 and 0.32 Hz in MBF and to a lesser extent RBF,
      but not CBF. MBF therefore appears to be less sensitive than CBF to the magnitude
      of RSNA, but it is more able to respond to these higher frequencies of neural
      stimulation.

PMID- 10956249
TI  - Excitation-induced Ca(2+) influx in rat soleus and EDL muscle: mechanisms and
      effects on cellular integrity.
AB  - In rat skeletal muscle, electrical stimulation increases Ca(2+) influx leading to
      progressive accumulation of calcium. Excitation-induced Ca(2+) influx in extensor
      digitorum longus (EDL; fast-twitch fibers) and soleus muscle (slow-twitch fibers)
      is compared. In EDL and soleus, stimulation at 40 Hz increased (45)Ca uptake 34-
      and 21-fold and (22)Na uptake 17- and 7-fold, respectively. These differences may
      be related to the measured 70% higher concentration of Na(+) channels in EDL.
      Repeated stimulation at 40 Hz elicited a delayed release of lactic acid
      dehydrogenase (LDH) from EDL (11-fold increase) and soleus (5-fold increase).
      Continuous stimulation at 1 Hz increased LDH release only from EDL (18-fold).
      This was associated with increased Ca(2+) content and was augmented at high
      extracellular Ca(2+) concentration ([Ca(2+)](o)) and suppressed at low
      [Ca(2+)](o). The data support the hypothesis that excitation-induced Ca(2+)
      influx is mediated in part by Na(+) channels and that the ensuing increase in
      intracellular Ca(2+) induces cellular damage. This is most pronounced in EDL,
      which may account for the repeated observation that prolonged exercise leads to
      preferential damage to fast-twitch fibers.

PMID- 10956250
TI  - Membrane mechanisms for electrogenic Na(+)-independent L-alanine transport in the
      lizard duodenal mucosa.
AB  - The active Na(+)-independent transport of L-alanine across the duodenal mucosa of
      the lizard Gallotia galloti was studied in Ussing-type chambers using a computer
      controlled voltage clamp. Addition of L-alanine to the Na(+)-free bathing
      solutions resulted in a significant L-alanine absorption (J(net)) that was
      paralleled by an increase in transepithelial short-circuit current (I(sc)) and
      potential difference (PD) without apparent changes in the tissue conductance. The
      concentration dependence of J(net), PD, and I(sc) displayed Michaelis-Menten
      kinetics. L-alanine-induced electrical changes were completely inhibited by
      external alkaline pH or by the H(+)-ionophore carbonyl cyanide m-chlorophenyl
      hydrazone in the bathing solution. The alanine-induced electrogenicity was
      dependent on the presence of extracellular K(+) and could be blocked by serosal
      Ba(2+) or mucosal orthovanadate. These results suggest the existence of an H(+)
      coupled L-alanine cotransport at the apical membrane of enterocytes. The
      favorable H(+) driving force is likely to be maintained by an apical vanadate
      sensitive H(+)-K(+)-ATPase, allowing the extrusion of H(+) in an exchange with
      K(+). Potassium exit through a basolateral barium-sensitive conductance provides
      the key step for the electrogenicity of L-alanine absorption.

PMID- 10956251
TI  - Subcutaneous lipectomy causes a metabolic syndrome in hamsters.
AB  - The insulin resistance syndrome X is related to excess intra-abdominal adipose
      tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in
      nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet
      and measurements of oral glucose tolerance, oral [(14)C]oleic acid disposal,
      serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue
      cellularity, and body composition, we studied the role of SQAT. Sham-operated (S)
      animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo
      there was no visible regrowth of SQAT but HF diet led to similar levels of body
      weight and body fat in lipectomized and sham-operated animals. Lipectomized (L)
      animals had more intra-abdominal fat as a percentage of total body fat, higher
      insulinemic index, a strong trend toward increased liver fat content, and
      markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR
      adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs.
      S-LF, and were inversely correlated with liver fat content and insulin sums
      during the oral glucose tolerance test. In summary, lipectomy of SQAT led to
      compensatory fat accumulation implying regulation of total body fat mass. In
      conjunction with HF diet these lipectomized hamsters developed a metabolic
      syndrome with significant hypertriglyceridemia, relative increase in intra
      abdominal fat, and insulin resistance. We propose that SQAT, via disposal and
      storage of excess ingested energy, acts as a metabolic sink and protects against
      the metabolic syndrome of obesity.

PMID- 10956252
TI  - Racial differences in lipid metabolism in women with abdominal obesity.
AB  - We evaluated palmitate rate of appearance (R(a)) in plasma during basal
      conditions and during a four-stage epinephrine infusion plus pancreatic hormonal
      clamp in nine white and nine black women with abdominal obesity, who were matched
      on fat-free mass, total and percent body fat, and waist-to-hip circumference
      ratio. On the basis of single-slice magnetic resonance imaging analysis, black
      women had the same amount of subcutaneous abdominal fat but less intra-abdominal
      fat than white women (68 +/- 9 vs. 170 +/- 14 cm(2), P < 0.05). Basal palmitate
      R(a) was lower in black than in white women (1.95 +/- 0.26 vs. 2.88 +/- 0.23
      micromol. kg fat-free mass(-1). min(-1), P < 0.005), even though plasma insulin
      and catecholamine concentrations were the same in both groups. Palmitate R(a)
      across a physiological range of plasma epinephrine concentrations remained lower
      in black women, because the increase in palmitate R(a) during epinephrine
      infusion was the same in both groups. We conclude that basal and epinephrine
      stimulated palmitate R(a) is lower in black than in white women with abdominal
      obesity. The differences in basal palmitate kinetics are not caused by
      alterations in plasma insulin or catecholamine concentrations or lipolytic
      sensitivity to epinephrine. The lower rate of whole body fatty acid flux and
      smaller intra-abdominal fat mass may have clinical benefits because of the
      relationship between excessive fatty acid availability and metabolic diseases.

PMID- 10956253
TI  - Intense exercise causes decrease in expression of both endothelial NO synthase
      and tissue NOx level in hearts.
AB  - Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense
      exercise on the expression of NO synthase (NOS) and the tissue level of nitrite
      (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in
      the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise,
      the heart was quickly removed. Control rats remained at rest during the same 45
      min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly
      lower in the exercised rats than in the control rats. Western blot analysis
      confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx
      level in the heart was significantly lower in the exercised rats than in the
      control rats. The present study revealed for the first time that production of NO
      in the heart is decreased by intense exercise. Because NO attenuates positive
      inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the
      heart, the decrease in cardiac production of NO by intense exercise may
      contribute to the acceleration of increase in myocardial contractility and heart
      rate during intense exercise.

PMID- 10956254
TI  - Vagal CCK and 5-HT(3) receptors are unlikely to mediate LPS or IL-1beta-induced
      fever.
AB  - Previous studies suggested that peripheral immune mediators may involve
      intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have
      therefore investigated a possible role for vagal CCK-A and 5-HT(3) receptors in
      the febrile response after intraperitoneal human recombinant interleukin-1beta
      (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats
      instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate
      (100 or 150 microgram/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In
      other experiments, rats were treated with either antagonists to the 5-HT(3)
      receptor (ondansetron HCl; 100 microgram/kg) or the CCK-A receptor (L-364,718,
      100 or 200 microgram/kg) in combination with LPS or IL-1beta. CCK administration
      caused a short-lived hypothermia, but interference with the action of endogenous
      CCK at CCK-A receptors was without effect on IL-1beta- or LPS-induced fever.
      Neither activation of 5-HT(3) receptors nor blockade of 5-HT(3) receptors
      affected body temperature or LPS fever. Taken together, our data support the idea
      that vagal afferents responsive to pyrogenic cytokines may be different from
      those responsive to CCK or 5-HT.

PMID- 10956255
TI  - Effects of time of day, gender, and menstrual cycle phase on the human response
      to a water load.
AB  - Estrogen and progesterone interference with renal actions of arginine vasopressin
      (AVP) has been shown. Thus we hypothesized that women will have a higher water
      turnover than men and that the greatest difference will be during the luteal
      phase of the menstrual cycle. Seven men (32 +/- 3 yr) and six women (33 +/- 2 yr)
      drank 12 ml water/kg lean body mass on different days at 0800 and at 2000
      following 10 h of fast and a standardized meal at 0600 and 1800. Women
      participated on days 4-11 and 19-25 of the menstrual cycle. Initial urine and
      plasma osmolalities and urine flow rates were similar in all experiments. The
      cumulative urine voided over 3 h following the morning drink was less in men (73
      +/- 12% of the water load) compared with women in either the follicular (100 +/-
      3%) or luteal phases (102 +/- 10%) of the menstrual cycle. Nighttime values (30
      43% of the water load) were lower in all experiments and were not different
      between sexes or menstrual cycle phases. Plasma AVP was higher at night and may
      contribute to this diurnal response. The data are generally consistent with the
      stated hypothesis; however, possibly owing to the greatly reduced urine flow in
      both sexes at night, a difference between sexes was not observed at that time.

PMID- 10956256
TI  - Activation of cardiorenal and pulmonary tissue endothelin-1 in experimental heart
      failure.
AB  - Endothelin-1 (ET-1) is a peptide that has been implicated in congestive heart
      failure (CHF). Although increased concentrations of circulating ET-1 have been
      repeatedly demonstrated, the activation of local ET-1 in target tissues of CHF
      remains poorly defined. Our objective was to characterize ET-1 tissue
      concentrations and gene expression of prepro ET-1 in myocardial, renal, and
      pulmonary tissue in rapid ventricular pacing-induced canine CHF. Progressive
      rapid ventricular pacing (38 days) resulted in impaired cardiovascular
      hemodynamics, increased atrial and left ventricular mass, decreased renal sodium
      excretion, and increased ET-1 plasma concentrations (all P < 0.05). Tissue
      analysis revealed significant increases in local ET-1 during CHF in left
      ventricular, renal, and pulmonary tissue, whereas a moderate increase in left
      atrial ET-1 did not reach statistical significance. In contrast, prepro-ET-1 gene
      expression was increased more than threefold in pulmonary tissue and more than
      twofold in left atrial myocardium with no increase in left ventricular or renal
      gene expression. The present studies demonstrate a differential pattern of ET-1
      activation in cardiorenal and pulmonary tissue with a strong accumulation of ET-1
      in kidney and lung during CHF. Although the observed increase in left ventricular
      and renal ET-1 in association with unaltered gene expression is consistent with
      increased uptake, pulmonary and atrial tissue may contribute to increased
      circulating and local ET-1 in CHF.

PMID- 10956257
TI  - Leukocyte-endothelial cell interactions in diabetic retina after transient
      retinal ischemia.
AB  - Diabetes is associated with increased neural damage after transient cerebral
      ischemia. Recently, leukocytes, which are thought to play a central role in
      ischemia-reperfusion injury, have been suggested to be involved in exacerbated
      damage after transient ischemia in diabetic animals. The present study was
      designed to clarify whether the anticipated worse outcome after transient
      cerebral ischemia in diabetic animals was due to augmented leukocyte-mediated
      neural injury. Using rats with streptozotocin-induced diabetes of 4-wk duration,
      we investigated leukocyte-endothelial cell interactions during reperfusion after
      a transient 60-min period of retinal ischemia. Unexpectedly, postischemic
      diabetic retina showed no active leukocyte-endothelial cell interactions during
      reperfusion. The maximal numbers of rolling and accumulating leukocytes in
      diabetic retina were reduced by 73.6 and 41.2%, respectively, compared with those
      in nondiabetic rats. In addition, neither preischemic insulin treatment of
      diabetic rats nor preischemic glucose infusion of nondiabetic rats significantly
      influenced leukocyte-endothelial cell interactions during reperfusion. The
      present study demonstrated that high blood glucose concentration before induction
      of ischemia did not exacerbate leukocyte involvement in the postischemic retinal
      injury. Furthermore, diabetic retina showed suppressed leukocyte-endothelial
      cells interactions after transient ischemia, perhaps due to an adaptive mechanism
      that developed during the period of induced diabetes.

PMID- 10956258
TI  - Norepinephrine mediates glucoprivic-induced increase in GABA in the ventromedial
      hypothalamus of rats.
AB  - Noradrenergic mechanisms in the hypothalamus may be involved in counterregulatory
      responses to glucoprivic episodes. After 2-deoxy-D-glucose (2-DG; 1.2 mmol/kg
      iv), extracellular norepinephrine (NE) concentration in the ventromedial
      hypothalamus (VMN) increased in a bimodal fashion to 251 +/- 39% (P < 0.001) and
      150 +/- 17% (P < 0.001) of baseline during the first 30 min. In the lateral
      hypothalamus (LHA), NE decreased by 30 min (61 +/- 4%, P < 0.001) and no
      consistent changes were measured in the paraventricular nucleus (PVN). Because
      the NE response in the VMN after 2-DG followed the same pattern as GABA, the
      interaction between NE and GABA was evaluated. In the VMN, GABA had little effect
      on extracellular NE concentrations but NE increased GABA concentrations 166 +/-
      13%, (P < 0.01). In the presence of yohimbine (alpha(2)-adrenoceptor antagonist)
      the first GABA peak after 2-DG was absent, and the second GABA peak was absent in
      the presence of timolol (beta-adrenoceptor antagonist). These results support an
      interaction among noradrenergic and GABAergic systems in the VMN during
      glucoprivation and that increased NE mediates the increase in extracellular GABA
      after 2-DG.

PMID- 10956259
TI  - Differential effects of selective vagotomy and tropisetron in aminoprivic
      feeding.
AB  - Both total subdiaphragmatic vagotomy (TVAGX) and serotonin(3) receptor blockade
      with tropisetron or ondansetron attenuate amino acid-imbalanced diet (Imb)
      anorexia. Total vagotomy is less effective than tropisetron in reducing Imb
      induced anorexia and also blunts the tropisetron effect. With the use of
      electrocautery at the subdiaphragmatic level of the vagus, we severed the ventral
      and dorsal trunks as well as the hepatic, ventral gastric, dorsal gastric,
      celiac, and accessory celiac branches separately or in combination to determine
      which vagal branches or associated structures may be involved in these responses.
      Rats were prefed a low-protein diet. On the first experimental day, tropisetron
      or saline was given intraperitoneally 1 h before presentation of Imb. Cuts
      including the ventral branch, i.e., TVAGX, ventral vagotomy (above the hepatic
      branch), and hepatic + gastric vagotomies (but not hepatic branch cuts alone)
      caused the highest (P < 0.05) Imb intake on day 1 with or without tropisetron.
      The responses to tropisetron were not affected significantly. On days 2-8, groups
      having vagotomies that included the hepatic branch recovered faster than sham
      treated animals. Because the hepatic and gastric branches together account for
      most of the vagal innervation to the proximal duodenum, this area may be
      important in the initial responses, whereas structures served by the hepatic
      branch alone apparently act in the later adaptation to Imb.

PMID- 10956260
TI  - Effect of severe normocapnic hypoxia on renal function in growth-restricted
      newborn piglets.
AB  - To examine the effects of intrauterine growth restriction and acute severe oxygen
      deprivation on renal blood flow (RBF), renovascular resistance (RVR), and renal
      excretory functions in newborns, studies were conducted on 1-day-old anesthetized
      piglets divided into groups of normal weight (NW, n = 14) and intrauterine growth
      restricted (IUGR, n = 14) animals. Physiological parameters, RBF, RVR, and
      urinary flow, were similar in NW and IUGR piglets, but glomerular filtration rate
      (GFR) and filtration fraction were significantly less in IUGR animals (P < 0.05).
      An induced 1-h severe hypoxia (arterial PO(2) = 19 +/- 4 mmHg) resulted in, for
      both groups, a pronounced metabolic acidosis, strongly reduced RBF, and increased
      fractional sodium excretion (FSE; P < 0.05) with a less-pronounced increase of
      RVR and arterial catecolamines in IUGR piglets. Of significance was a smaller
      decrease in RBF for IUGR piglets (P < 0.05). Early recovery showed a transient
      period of diuresis with increased osmotic clearance and elevated FSE in both
      groups (P < 0.05). However, GFR and renal O(2) delivery remained reduced in NW
      piglets (P < 0.05). We conclude that, in newborn IUGR piglets, RBF is maintained,
      although GFR is compromised. Severe hypoxemia induces similar alterations of
      renal excretion in newborn piglets. However, the less-pronounced RBF reduction
      during hypoxemia indicates an improved adaptation of newborn IUGR piglets on
      periods of severely disturbed oxygenation. Furthermore, newborn piglets
      reestablish the ability for urine concentration and adequate sodium reabsorption
      early after reoxygenation so that a sustained acute renal failure was prevented.

PMID- 10956261
TI  - Role of the renin-angiotensin system in regulation and autoregulation of renal
      blood flow.
AB  - The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The
      present study was designed to test the effect of clamping plasma ANG II
      concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting
      enzyme inhibitor captopril and ANG II on RBF autoregulation in halothane
      anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response
      to acute changes in renal perfusion pressure (RPP). Regulation was defined as
      changes in RBF during long-lasting changes in RPP. The results showed that a
      prolonged reduction of RPP reset the lower limit of autoregulation from 85 +/- 1
      to 73 +/- 2 mmHg (P < 0.05) and regulated RBF to a lower level. Reduction of RPP
      to just above the lower limit of autoregulation (88 mmHg) induced regulation of
      RBF to a lower level within 10 min. Clamping [ANG II] per se reset the lower
      limit of autoregulation to 62 +/- 5 mmHg. In this case, reduction in RPP to 50
      mmHg did not induce a downregulation of RBF. We conclude that ANG II plays an
      important role in the resetting of the autoregulation limits. The ability to
      regulate RBF to a new level as a response to changes in RPP also depends on
      changes in [ANG II].

PMID- 10956262
TI  - Regulation of food intake by neuropeptide Y in goldfish.
AB  - In mammals, neuropeptide Y (NPY) is a potent orexigenic factor. In the present
      study, third brain ventricle (intracerebroventricular) injection of goldfish NPY
      (gNPY) caused a dose-dependent increase in food intake in goldfish, and
      intracerebroventricular administration of NPY Y1-receptor antagonist BIBP-3226
      decreased food intake; the actions of gNPY were blocked by simultaneous injection
      of BIBP-3226. Goldfish maintained on a daily scheduled feeding regimen display an
      increase in NPY mRNA levels in the telencephalon-preoptic area and hypothalamus
      shortly before feeding; however, a decrease occured in optic tectum-thalamus. In
      both fed and unfed fish, brain NPY mRNA levels decreased after scheduled feeding.
      Restriction in daily food ration intake for 1 wk or food deprivation for 72 h
      resulted in increased brain NPY mRNA levels. Results from these studies
      demonstrate that NPY is a physiological brain signal involved in feeding behavior
      in goldfish, mediating its effects, at least in part, through Y1-like receptors
      in the brain.

PMID- 10956263
TI  - Systolic pressure predicts plasma vasopressin responses to hemorrhage and vena
      caval constriction in dogs.
AB  - We have proposed that the reflex increase in arginine vasopressin (AVP) secretion
      in response to hypovolemia is due to arterial baroreceptor unloading. If arterial
      pressure is the key to the mechanism, the slope relating plasma AVP to arterial
      pressure should be the same in response to hemorrhage, a model of true
      hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC),
      a model of central hypovolemia. We tested this hypothesis in conscious,
      chronically instrumented dogs (n = 8). The mean coefficient of determination
      (r(2)) values obtained from the individual regressions of log AVP onto systolic
      pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were
      0.953 +/- 0.009 and 0.845 +/- 0.047, respectively. Paired comparisons indicated a
      significant difference between the means (P < 0.05), hence, SP was used in
      subsequent analyses. The mean slopes relating the log of plasma AVP to SP in
      response to hemorrhage and IVCC were -0.034 +/- 0.003 and -0.032 +/- 0.002,
      respectively, and the means were not significantly different (P = 0.7). The
      slopes were not altered when the experiments were repeated during acute blockade
      of cardiac receptors by intrapericardial procaine. Finally, sinoaortic
      denervation (n = 4) markedly reduced the slope in both the hemorrhage and IVCC
      treatments. We conclude that baroreceptors monitoring arterial pressure provide
      the principal reflex control of AVP secretion in response to hypovolemia.

PMID- 10956264
TI  - Macrophage migration inhibitory factor antagonizes hydrocortisone-induced
      increases in cytosolic IkappaBalpha.
AB  - Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine secreted
      by several cell types, including mononuclear and pituitary cells. It has also
      been shown to counteract cortisol-induced inhibition of inflammatory cytokine
      secretion. The purpose of this study was to determine whether MIF antagonized the
      effect of hydrocortisone on the NF-kappaB/IkappaB signal transduction pathway in
      lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells.
      Physiological doses of hydrocortisone (50-200 ng/ml) diminished both the LPS
      stimulated decrease in cytosolic IkappaBalpha levels and the subsequent increase
      in nuclear NF-kappaB DNA binding. In the presence of both LPS and hydrocortisone,
      1 ng/ml of MIF antagonized the effects of hydrocortisone, resulting in decreased
      cytosolic IkappaBalpha levels (P < 0.05) and increased nuclear NF-kappaB DNA
      binding (P < 0.05). In the absence of hydrocortisone, MIF had no effect on LPS
      induced decreases in IkappaBalpha. In the absence of LPS, MIF inhibited
      hydrocortisone-induced increases in IkappaBalpha (P = 0.03). Thus the mechanism
      by which MIF antagonizes the effect of hydrocortisone on the NF-kB/IkappaB signal
      transduction pathway is through inhibiting the ability of hydrocortisone to
      increase cytosolic IkappaBalpha.

PMID- 10956265
TI  - IGF-I treatment attenuates renal abnormalities induced by neonatal ACE
      inhibition.
AB  - An intact renin-angiotensin system (RAS) during nephrogenesis is essential for
      normal renal development. We have shown previously that neonatal inhibition of
      the RAS, either with ANG II type 1-receptor blockade or angiotensin-converting
      enzyme (ACE) inhibition, induces irreversible renal abnormalities. The aim of the
      present study was to investigate whether an interrupted RAS can be compensated
      for by exogenous administration of another important renal growth-promoting
      factor, the insulin-like growth factor-I (IGF-I). Rats were treated daily with
      either the ACE inhibitor enalapril (10 mg/kg), recombinant human IGF-I (3 mg/kg),
      or the combination enalapril + IGF-I from perinatal day 3 to 13. Urinary
      concentrating ability, renal function, and renal morphology were assessed at
      adult age. The gene expression and localization of IGF-I, its receptor, and the
      growth hormone receptor (GHR) were investigated during ongoing ACE inhibition.
      The present study demonstrates normalized renal function and histology in
      enalapril + IGF-I-treated animals. Ongoing ACE inhibition suppressed the
      medullary IGF-I mRNA expression and altered the local distribution of both IGF-I
      and GHR. Thus the present study provides evidence for an interaction between the
      RAS and GH/IGF-I axis in renal development.

PMID- 10956266
TI  - Oxytocin modulates the onset of murine parturition by competing ovarian and
      uterine effects.
AB  - Recent analysis of mice deficient in both oxytocin (OT) and cyclooxygenase-1 has
      shown that OT exerts significant effects on both the ovarian corpus luteum and
      the uterine myometrium during pregnancy. To better define the roles of OT during
      pregnancy, we evaluated OT action and OT receptor regulation in wild-type and OT
      deficient knockout (KO) mice. Continuous infusion of OT revealed that OT can
      either delay labor at low doses or initiate preterm labor at high doses. The
      infusion rates of OT necessary for these effects were reduced in OT KO mice. The
      dose of OT that delayed labor also delayed the normal decrease in plasma
      progesterone late in gestation, implicating a primary effect on the corpus
      luteum. Consistent with this hypothesis, luteal OT receptor expression exceeded
      that of the myometrium until luteolysis occurred. We propose that the
      downregulation of OT receptors in the corpus luteum and induction of OT receptors
      in the myometrium serve to shift the predominant consequence of OT action during
      murine pregnancy from labor inhibition to labor promotion.

PMID- 10956267
TI  - Validity of VO(2 max) in predicting blood volume: implications for the effect of
      fitness on aging.
AB  - A multiple regression model was constructed to investigate the premise that blood
      volume (BV) could be predicted using several anthropometric variables, age, and
      maximal oxygen uptake (VO(2 max)). To test this hypothesis, age, calculated body
      surface area (height/weight composite), percent body fat (hydrostatic weight),
      and VO(2 max) were regressed on to BV using data obtained from 66 normal healthy
      men. Results from the evaluation of the full model indicated that the most
      parsimonious result was obtained when age and VO(2 max) were regressed on BV
      expressed per kilogram body weight. The full model accounted for 52% of the total
      variance in BV per kilogram body weight. Both age and VO(2 max) were related to
      BV in the positive direction. Percent body fat contributed <1% to the explained
      variance in BV when expressed in absolute BV (ml) or as BV per kilogram body
      weight. When the model was cross validated on 41 new subjects and BV per kilogram
      body weight was reexpressed as raw BV, the results indicated that the statistical
      model would be stable under cross validation (e.g., predictive applications) with
      an accuracy of +/- 1,200 ml at 95% confidence. Our results support the hypothesis
      that BV is an increasing function of aerobic fitness and to a lesser extent the
      age of the subject. The results may have implication as to a mechanism by which
      aerobic fitness and activity may be protective against reduced BV associated with
      aging.

PMID- 10956268
TI  - Skeletal muscle myosin heavy chain isoforms and energy metabolism after
      clenbuterol treatment in the rat.
AB  - Prolonged treatment with the beta(2)-adrenoceptor agonist clenbuterol (1-2 mg. kg
      body mass(-1). day (-1)) is known to induce the hypertrophy of fast-contracting
      fibers and the conversion of slow- to fast-contracting fibers. We investigated
      the effects of administering a lower dose of clenbuterol (250 microgram. kg body
      mass(-1). day (-1)) on skeletal muscle myosin heavy chain (MyHC) protein isoform
      content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar
      rats were administered clenbuterol (n = 8) or saline (n = 6) subcutaneously for 8
      wk, after which the extensor digitorum longus (EDL) and soleus muscles were
      removed. We demonstrated an increase of type IIa MyHC protein content in the
      soleus from approximately 0.5% in controls to approximately 18% after clenbuterol
      treatment (P < 0.05), which was accompanied by an increase in the total adenine
      nucleotide pool (TAN; approximately 19%, P < 0.05) and energy charge [E-C = (ATP
      + 0.5 ADP)/(ATP + ADP + AMP); approximately 4%; P < 0.05]. In the EDL, a
      reduction in the content of the less prevalent type I MyHC protein from
      approximately 3% in controls to 0% after clenbuterol treatment (P < 0.05)
      occurred without any alterations in TAN and E-C. These findings demonstrate that
      the phenotypic changes previously observed in slow muscle after clenbuterol
      administration at 1-2 mg. kg body mass(-1). day(-1) are also observed at a
      substantially lower dose and are paralleled by concomitant changes in cellular
      energy metabolism.

PMID- 10956269
TI  - Prostaglandin dehydrogenase mRNA in baboon intrauterine tissues in late gestation
      and spontaneous labor.
AB  - The present study was designed to characterize prostaglandin dehydrogenase (PGDH)
      mRNA expression in critical intrauterine tissues of pregnant baboons in late
      gestation and at spontaneous labor. In addition, we determined regulatory effects
      of betamethasone in vivo on chorionic and placental PGDH mRNA expression. PGDH
      mRNA was present in chorion, decidua, lower uterine segment, fundal myometrium,
      and cervix in late gestation but undetectable in amnion. PGDH mRNA significantly
      decreased in decidua and cervix during late gestation and in chorion and fundus
      during spontaneous labor. PGDH mRNA in lower uterine segment, decidua, cervix,
      and placenta was unchanged during spontaneous labor from late gestation levels.
      Betamethasone had no effect on chorionic and placental PGDH mRNA expression. In
      summary, our data suggest that PGDH mRNA expression is tightly controlled in
      gestation- and tissue-specific manners. Decreased chorionic and fundal PGDH
      abundance during labor and decreased decidua and cervical PGDH mRNA in late
      gestation allow local uterine prostaglandin accumulation and assist prostaglandin
      transfer to myometrium. Local differences in PGDH function may regulate tissue-
      and region-specific requirements for prostaglandins to promote and complete
      labor.

PMID- 10956270
TI  - Ontogeny of cholinergic and adrenergic cardiovascular regulation in the domestic
      chicken (Gallus gallus).
AB  - Adrenergic and cholinergic tone on the cardiovascular system of embryonic
      chickens was determined during days 12, 15, 19, 20, and 21 of development.
      Administration of the muscarinic antagonist atropine (1 mg/kg) resulted in no
      significant change in heart rate or arterial pressure at any developmental age.
      In addition, the general cardiovascular depressive effects of hypoxia were
      unaltered by pretreatment with atropine. In addition, the ganglionic blocking
      agent hexamethonium (25 mg/kg) did not induce changes in heart rate. The beta
      adrenergic antagonist propranolol (3 mg/kg) induced a bradycardia of similar
      magnitude on all days studied, with a transient hypertensive action on days 19
      20, indicating the existence of an important cardiac and vascular beta-adrenergic
      tone. Injections of the alpha-adrenergic antagonists prazosin or phentolamine (1
      mg/kg) reduced arterial pressure significantly on all days of incubation studied.
      Collectively, the data indicate that embryonic chickens rely primarily on
      adrenergic control of cardiovascular function, with no contribution from the
      parasympathetic nervous system.

PMID- 10956271
TI  - Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat
      kidney.
AB  - Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from
      normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To
      investigate whether renal sodium retention precedes the development of
      posttransplantation hypertension in recipients of an SHR kidney on a standard
      sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1
      hybrids, measured daily sodium balances during the first 12 days after removal of
      both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk.
      Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a
      WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/-
      6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY
      kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of
      recipients of an SHR kidney (n = 10) did not prevent posttransplantation
      hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion
      rates were similar in recipients of an SHR and a WKY kidney. Transient excess
      sodium retention after renal transplantation may contribute to
      posttransplantation hypertension in recipients of an SHR kidney.

PMID- 10956272
TI  - Role of the renin-angiotensin system in drinking of seawater-adapted eels
      Anguilla japonica: a reevaluation.
AB  - The role of ANG II, a potent dipsogenic hormone, in copious drinking of seawater
      eels was examined. SQ-14225 (SQ), an angiotensin-converting enzyme inhibitor,
      infused intra-arterially at 0.01-1 microgram. kg(-1). min(-1), depressed drinking
      and arterial blood pressure in a dose-dependent manner. The inhibition was
      accompanied by a small decrease in plasma ANG II concentration, which became
      significant at 1 microgram. kg(-1). min(-1). After the infusate was changed back
      to the vehicle, the depression of drinking and arterial pressure continued for >2
      h, although plasma ANG II concentration rebounded above the level before SQ
      infusion. By contrast, infusion of anti-ANG II serum (0.01-1 microgram. kg(-1).
      min(-1)) did not suppress drinking and arterial pressure, although plasma ANG II
      concentration decreased to undetectable levels. Plasma atrial natriuretic peptide
      and plasma osmolality, which influence drinking rate in eels, did not change
      during SQ or antiserum infusions. These results suggest that the renin
      angiotensin system plays only a minor role in the vigorous drinking observed in
      seawater eels. The results also suggest that the antidipsogenic and vasodepressor
      effects of SQ in seawater eels are not due solely to the inhibition of ANG II
      formation in plasma.

PMID- 10956273
TI  - Functional characteristics of urinary tract smooth muscles in mice lacking cGMP
      protein kinase type I.
AB  - Nitric oxide (NO)-mediated smooth muscle relaxation is mediated by cGMP through
      activation of cGMP-dependent protein kinase I (cGKI). We studied the importance
      of cGKI for lower urinary tract function in mice lacking the gene for cGKI (cGKI
      /-) and in litter-matched wild-type mice (cGKI+/+) in vitro and in vivo. cGKI
      deficiency did not result in any changes in bladder gross morphology or weight.
      Urethral strips from cGKI-/- mice showed an impaired relaxant response to nerve
      derived NO. The cGMP analog 8-bromo-cGMP (8-BrcGMP) and the NO-donor SIN-1
      relaxed the wild-type urethra (50-60%) but had only marginal effects in the cGKI
      deficient urethra. Bladder strips from cGKI-/- mice responded normally to
      electrical field stimulation and to carbachol but not to 8-BrcGMP. In vivo, the
      cGKI-deficient mice showed bladder hyperactivity characterized by decreased
      intercontraction intervals and nonvoiding bladder contractions. Loss of cGKI
      abolishes NO-cGMP-dependent relaxations of urethral smooth muscle and results in
      hyperactive voiding. These data suggest that certain voiding disturbances may be
      associated with impaired NO-cGKI signaling.

PMID- 10956274
TI  - Rapid induction of sodium appetite modifies taste-evoked activity in the rat
      nucleus of the solitary tract.
AB  - Sodium-deprived rats develop a salt appetite and show changes in gustatory
      responses to NaCl in the periphery and brain stem; salt-sensitive neurons respond
      less to hypertonic NaCl than do corresponding cells in replete controls. By
      administering DOCA and renin, we generated a need-free sodium appetite quickly
      enough to permit us to monitor the activity of individual neurons in the nucleus
      of the solitary tract before and after its creation, permitting a more powerful
      within-subjects design. Subjects received DOCA pretreatment followed by an
      intracerebroventricular infusion of renin. In animals that were tested
      behaviorally, this resulted in elevated intake of 0.5 M NaCl. In neural
      recordings, renin caused decreased responding to hypertonic NaCl across all
      neurons and in the salt-sensitive neurons that were most responsive to NaCl
      before infusion. Most sugar-sensitive cells, in contrast, gave increased phasic
      responses to NaCl. These results confirm that sodium appetite is accompanied by
      decreased responding to NaCl in salt-sensitive neurons, complemented by increased
      activity in sugar-sensitive cells, even when created rapidly and independently of
      need.

PMID- 10956275
TI  - Short photoperiods reduce vascular endothelial growth factor in the testes of
      Peromyscus leucopus.
AB  - Testicular regression in rodents occurs after short-day exposure. Vascular
      support is withdrawn during regression, and, presumably, new angiogenesis is
      inhibited. Blood vessel growth and maintenance are regulated by paracrine
      factors, including vascular endothelial growth factor (VEGF). Reduced
      angiogenesis may contribute to the onset of photoperiod-induced regression; i.e.,
      reduction of VEGF protein would be detected early during gonadal atrophy.
      Alternatively, loss of blood vessel maintenance may reflect reduced testicular
      volume. If true, VEGF would not be expected to decline until significant
      regression occurred. To discriminate between these hypotheses, white-footed mice
      (Peromyscus leucopus) were maintained in either long (LD 16:8) or short (LD 8:16)
      photoperiod. Immunohistochemical and Western analyses revealed high VEGF
      expression in Leydig and Sertoli cells in long-day housed males and reduced VEGF
      expression in short-day housed males. Reductions in VEGF preceded decreases in
      both seminiferous tubule diameter and spermatogenic activity by 6 wk and reduced
      testis mass by 8 wk, suggesting that changes in VEGF are not a consequence of
      gonadal regression and that VEGF may play a critical role in photoperiodic
      regulation of testicular function.

PMID- 10956276
TI  - Single exposure to stressors causes long-lasting, stress-dependent reduction of
      food intake in rats.
AB  - A single exposure to severe stressors has been shown to cause anorexia in the
      next 24 h, but the duration of such alterations is not known. Male Sprague-Dawley
      rats were subjected to different stressors, and food intake was measured for
      several days after stress. In experiment 1, 2 h of immobilization (Imo) and
      lipopolysaccharide (LPS) administration (1,000 microgram/kg) caused a marked
      anorexia in the 24 h after stress, which persisted on poststress day 3. In
      experiment 2, changes in food intake after LPS and Imo were followed until total
      recovery. As in experiment 1, LPS caused initially a greater degree of anorexia
      than Imo, but normal food intake recovered much faster (poststress day 3 vs.
      poststress day 9). Changing the period of exposure to Imo between 20 min and 6 h
      (experiment 3) only slightly modified the pattern of response to the stressor.
      When different doses of LPS (50, 250, and 1,000 microgram/kg) were tested in
      experiment 4, a dose-dependent effect on food intake was observed, the greatest
      doses causing the most marked and lasting effect. The present results showed
      stressor-specific lasting changes in food intake caused by a single exposure to
      some stressors, the effect of a severe psychological stressor such as Imo being
      more lasting than that of LPS, despite a lower initial anorexia. A severe
      psychological stressor and a physical stressor such as LPS appear to change food
      intake in different ways.

PMID- 10956277
TI  - Weight cycling-induced alteration in fatty acid metabolism.
AB  - Epidemiological studies have suggested that repeated weight cycling over time may
      increase the risk of coronary heart disease. The mechanism involved remains
      poorly understood, but the change in lipid metabolism during weight cycling has
      been offered as a possible explanation. The present study investigated the effect
      of weight cycling on the size and fatty acid composition of rat fat pads as well
      as serum cholesterol, triglyceride, glucose, insulin, and glucagon in rats. Two
      consecutive weight cycles were induced by 40% energy restriction followed by ad
      libitum refeeding of either a moderate-fat (MF; 22% energy) or a high-fat (HF;
      45% energy) diet. The lipogenic enzymes, including fatty acid synthase, acetyl
      CoA carboxylase, malic enzyme, pyruvate kinase, and lipoprotein lipase in the
      weight-cycled (WC) rats fed only the HF diet, yielded an overshoot of activities
      at the end of two weight cycles. These changes were accompanied by an 80%
      increase in the size of the adipocyte and a 40-50% increase in the size of
      perirenal and epididymal fat tissues in HF-WC rats. Regardless of whether the
      rats were fed the HF or MF diet, all WC rats showed a gradual reduction in
      linoleic and alpha-linolenic acid and an increase in palmitic, palmitoleic, and
      stearic acid in total body lipid. It is concluded that weight cycling in rats may
      promote body fatness if an HF diet is consumed and can significantly alter whole
      body fatty acid balance irrespective of whether they consumed an MF or HF diet.
      Most importantly, the weight cycling led to an overshoot or fluctuation of serum
      cholesterol, triglyceride, glucose, insulin, and glucagon. If weight cycling is
      associated with an increased risk of cardiovascular disease, then, part of the
      mechanism may involve the changes in these risk factors.

PMID- 10956278
TI  - Does smoking cessation reduce the risk of restenosis following coronary
      angioplasty?

PMID- 10956280
TI  - The pause that refreshes, or does it? Mechanisms in torsades de pointes.

PMID- 10956282
TI  - Images in cardiology: double orifice mitral valve.

PMID- 10956281
TI  - Coronary heart disease incidence in northern and southern European populations: a
      reanalysis of the seven countries study for a European coronary risk chart.
AB  - OBJECTIVE: A systematic reanalysis of 10 year coronary heart disease incidence
      data from the northern and the southern European cohorts of the seven countries
      study, to contribute indirectly to the production of a European coronary risk
      chart. DESIGN AND SETTING: Men aged 40-59 years at entry were studied in three
      northern European cohorts based in Finland and Netherlands (n = 2213); and in 10
      southern European cohorts based in Italy, former Yugoslavia, and Greece (n =
      5897). Multiple logistic models for the prediction of coronary deaths, coronary
      incidence (hard criteria), and coronary incidence (any criterion) were solved for
      the two geographical groups and their pool. Risk factors fed into the models were
      age, systolic blood pressure, serum total cholesterol, and cigarette smoking.
      RESULTS: 10 year coronary heart disease mortality and incidence were higher in
      northern than in southern Europe, with ratios around 2.65. Ratios among the three
      coronary heart disease manifestations were identical in the two cultural
      groupings. Coefficients of the multiple logistic models were similar and not
      significantly different between the two groupings. When applying the coefficients
      back to the same or the opposite population, the relative risk was large and
      similar in the different cultures. Relative risk was larger for more severe
      coronary heart disease manifestations. The absolute risk was overestimated when
      applying the northern European model to southern European populations and vice
      versa, with ratios of about 1.5 and 0.5, respectively. Coronary risk charts
      created to reproduce the shape of those incorporated in recent European
      guidelines confirmed the excess of absolute risk in the northern compared with
      the southern European cohorts, all else being equal. CONCLUSIONS: In theory, a
      more appropriate European coronary risk chart could be produced by adopting
      coefficients to correct for different background incidence rates in different
      cultures. Other coefficients could appropriately be used to transform mortality
      risk into incidence risk.

PMID- 10956283
TI  - Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy
      in the differential diagnosis.
AB  - OBJECTIVE: To test the hypothesis, using endomyocardial biopsies, that
      unexplained cases of apparent acute myocardial infarction were caused by
      myocarditis. MATERIAL: Between 1992 and 1998, 12 patients were admitted to the
      coronary care unit with severe chest pain, ST segment elevation, increased serum
      creatine kinase and MB isoenzyme, and with wall motion abnormalities on
      echocardiogram highly suggestive of acute myocardial infarction. These patients
      were further investigated by endomyocardial biopsy, as their coronary angiograms
      were normal. A diagnosis of myocarditis was made according to the Dallas
      criteria. A panel of antibodies was used for immunohistochemical characterisation
      of inflammatory cell infiltrate. Polymerase chain reaction (PCR) was used to
      detect viral genomes in seven cases. RESULTS: Haematoxylin and eosin staining of
      the endomyocardial biopsy showed active myocarditis in six patients and
      borderline myocarditis in one. Immunohistochemistry was positive for inflammatory
      cell infiltrates in 11 patients, including all the seven who were positive on
      haematoxylin and eosin staining according to the Dallas criteria. Only one
      patient had no evidence of inflammation. PCR was positive in two patients, both
      for Epstein-Barr virus. Follow up showed complete resolution of echocardiographic
      abnormalities in all patients except one. CONCLUSIONS: Myocarditis can mimic
      acute myocardial infarction in patients with angiographically normal coronary
      arteries, leading to errors of treatment. In patients with apparent myocardial
      infarction and a normal coronary angiogram, endomyocardial biopsy may help in the
      diagnosis of myocarditis. The sensitivity of endomyocardial biopsy was enhanced
      by using immunohistochemical and molecular biological techniques.

PMID- 10956286
TI  - Improving door to needle times with nurse initiated thrombolysis.
AB  - OBJECTIVE: To evaluate the effect of nurse initiated thrombolysis on door to
      needle time (the interval between arriving at the hospital and starting
      thrombolytic treatment) in patients with acute myocardial infarction. DESIGN:
      Comparison of door to needle times before and after the employment of nurses
      trained and approved to initiate thrombolysis without prescription by a doctor
      but with a protocol for rapid triage of patients with chest pain. SETTING: A
      district general hospital. SUBJECTS: All patients admitted with suspected
      myocardial infarction between April 1995 and March 1999. MAIN OUTCOME MEASURES:
      Speed (door to needle time) and appropriateness of administration of thrombolytic
      drugs to patients with acute myocardial infarction who gave a characteristic
      history and had appropriate criteria on the admission ECG. RESULTS: During seven
      periods (each of four months) before the introduction of nurse initiated
      thrombolysis and a new chest pain triage protocol, the median door to needle time
      varied from 50-58 minutes. In four periods (each of 4-6 months) following the
      introduction of the changes, the median door to needle time was 25-30 minutes.
      The improvement was significant (p < 0.001). Nurses trained to initiate
      thrombolysis currently provide cover for 66% of the time. Median door to needle
      time for nurses was 15 minutes. Median door to needle time for junior doctors
      improved to 35 minutes. The median door to needle times when nurses initiated
      thrombolysis was significantly shorter than when doctors did so (p < 0.001).
      There have been no inappropriate management decisions by nurses approved to
      initiate thrombolysis. CONCLUSIONS: The use of nurse initiated thrombolysis has
      resulted in a clinically important reduction in the time taken for thrombolysis
      to be started in patients with acute myocardial infarction.

PMID- 10956285
TI  - Prognostic implications of ventricular fibrillation in acute myocardial
      infarction: new strategies required for further mortality reduction.
AB  - OBJECTIVE: To determine the changing risk of ventricular fibrillation, the
      prognostic implications, and the potential long term prognostic benefit of
      earlier hospital admission, after acute myocardial infarction. DESIGN:
      Prospective observational study. SETTING: A district general hospital in east
      London. PATIENTS: 1225 consecutive patients admitted to a coronary care unit with
      acute myocardial infarction. MAIN OUTCOME MEASURES: Time of onset of pain and
      ventricular fibrillation, and long term survival of patients admitted with acute
      myocardial infarction. RESULTS: The rate of ventricular fibrillation in these
      hospital inpatients was high in the first hour from onset of pain (118
      events/1000 persons/h; 95% confidence interval (CI) 50.7 to 231) and fell rapidly
      to an almost constant low level by six hours; 27.4% of patients with early
      ventricular fibrillation died in hospital, compared with 11.6% of those without
      (p < 0.0001), but mortality in patients who survived to hospital discharge was
      not altered by early ventricular fibrillation (five year survival: 75.0% (95% CI
      60.0% to 84.8%) with ventricular fibrillation v 73.3% (95% CI 69.6% to 76.6%)
      without ventricular fibrillation). CONCLUSIONS: Patients successfully
      resuscitated from early ventricular fibrillation have the same prognosis as those
      without ventricular fibrillation after acute myocardial infarction. Faster access
      to facilities for resuscitation must be achieved if major improvements in the
      persistently high case fatality of patients after acute myocardial infarction are
      to be made.

PMID- 10956284
TI  - Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial
      fibrillation: a comparative, placebo controlled study.
AB  - OBJECTIVE: To assess and compare the safety and efficacy of amiodarone and
      sotalol in the treatment of patients with recurrent symptomatic atrial
      fibrillation. DESIGN: Prospective, randomised, single blind, placebo controlled
      study. SETTING: Tertiary cardiac referral centre. PATIENTS: 186 consecutive
      patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent,
      symptomatic atrial fibrillation. INTERVENTIONS: 65 patients were randomised to
      amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were
      maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose
      was 160-480 mg daily, as tolerated. MAIN OUTCOME MEASURES: Recurrence of atrial
      fibrillation or side effects. RESULTS: In the amiodarone group, 31 of the 65
      patients developed atrial fibrillation after an average of six months, while 15
      (11 in sinus rhythm and four in atrial fibrillation) experienced significant side
      effects after an average of 16 months. In the sotalol group, relapse to atrial
      fibrillation occurred in 47 of the 61 patients after an average of eight months;
      three experienced side effects during the titration phase. In the placebo group,
      53 of the 60 patients developed atrial fibrillation after an average of four
      months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone
      v sotalol). CONCLUSIONS: Both amiodarone and sotalol can be used for the
      maintenance of normal sinus rhythm in patients with symptomatic atrial
      fibrillation. Amiodarone is more effective but causes more side effects.

PMID- 10956287
TI  - Significant association of cagA positive Helicobacter pylori strains with risk of
      premature myocardial infarction.
AB  - OBJECTIVE: To investigate whether genetic diversity of Helicobacter pylori
      influences its association with coronary heart disease, and specifically whether
      the risk is confined to infection with the more virulent strains bearing the
      cytotoxin associated gene-A (cagA) antigen. DESIGN AND SETTING: Case-control
      study in hospital admitting unselected patients with myocardial infarction.
      METHODS AND SUBJECTS: Serological status for cagA and H pylori were determined in
      342 cases of acute myocardial infarction and 214 population based control
      subjects free of clinical coronary heart disease. RESULTS: 38.0% of cases and
      30.8% of controls were cagA seropositive (odds ratio 1.38, 95% confidence
      interval (CI) 0.94 to 2.01, p = 0.08). In subjects < 65 years old (153 cases, 153
      controls), cagA seropositivity was associated with a 1.80-fold increase (95% CI
      1.07 to 3.03, p = 0.02) in myocardial infarction risk, which increased further to
      2.25-fold (95% CI 1.12 to 4.53, p = 0.01) in subjects < 55 years. There was no
      significant association of cagA status with classical coronary heart disease risk
      factors. H pylori seropositivity was present in 60.2% of cases and 53.7% of
      controls (odds ratio 1.12, 95% CI 0.83 to 1.51, p = 0.43). H pylori
      seropositivity was not increased in young cases and did not show any interaction
      with age. CONCLUSIONS: The association of chronic H pylori infection with risk of
      myocardial infarction appears to be restricted to cagA bearing strains. The
      association is age dependent and stronger in younger subjects. Genetic
      heterogeneity of H pylori may explain some of the discordant findings with regard
      to the association of H pylori with coronary heart disease.

PMID- 10956288
TI  - Images in cardiology: mycotic aneurysm formation with dehiscence of a valved
      aortic conduit resulting in dynamic aortic obstruction.

PMID- 10956289
TI  - Different effects of abnormal activation and myocardial disease on left
      ventricular ejection and filling times.
AB  - BACKGROUND: Ventricular activation is often abnormal in patients with dilated
      cardiomyopathy, but its specific effects on timing remain undetermined.
      OBJECTIVE: To investigate the use of the ratio of the sum of left ventricular
      ejection and filling times to the total RR interval (Z ratio) to dissociate the
      effects of abnormal activation from those of cavity dilatation. METHODS: Subjects
      were 20 normal individuals, 11 patients with isolated left bundle branch block
      (LBBB, QRS duration > 120 ms), 17 with dilated cardiomyopathy and normal
      activation, and 23 with dilated cardiomyopathy and LBBB. An additional 30
      patients (nine with normal ventricular systolic function and 21 with dilated
      cardiomyopathy) were studied before and after right ventricular pacing. Left
      ventricular ejection and filling times were measured by pulsed wave Doppler and
      cavity size by M mode echocardiography. RESULTS: Z ratio was independent of RR
      interval in all groups. Mean (SD) Z ratio was 82 (10)% for normal subjects, 66
      (10)% for isolated LBBB (p < 0.01 v normal), 77 (7)% for dilated cardiomyopathy
      without LBBB (NS v normal), and 61 (7)% for dilated cardiomyopathy with LBBB (p <
      0.01 v normal). In the nine patients with normal left ventricular size and QRS
      duration, Z ratio fell from 88 (6)% in sinus rhythm to 77 (10)% with right
      ventricular pacing (p = 0.26). In the 21 patients with dilated cardiomyopathy and
      LBBB, Z ratio rose from 59 (10)% in sinus rhythm to 74 (9)% with right
      ventricular DDD pacing (p < 0.001). CONCLUSIONS: Z ratio dissociates the effects
      of abnormal ventricular activation and systolic disease. It also clearly
      differentiates right ventricular pacing from LBBB. It may thus be useful in
      comparing the haemodynamic effects of different pacing modes in patients with or
      without left ventricular disease.

PMID- 10956292
TI  - Images in cardiology: coronary sinus ostial atresia with persistent left superior
      vena cava connected with atrial septal defect.

PMID- 10956291
TI  - Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood
      flow alters lung mechanics.
AB  - BACKGROUND: Postoperative pulmonary hypertension in children after congenital
      heart surgery is a risk factor for death and is associated with severe acute
      changes in both pulmonary vascular resistance and lung mechanics. OBJECTIVE: To
      examine the impact of changes in pulmonary blood flow on lung mechanics in
      preoperative children with congenital heart disease, in order to assess the cause
      effect relation of pulmonary vascular-bronchial interactions. DESIGN:
      Prospective, cross sectional study. SETTING: Cardiac catheterisation laboratory,
      general anaesthesia with mechanical ventilation. INTERVENTIONS: Variation of
      pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect
      before interventional closure, or by complete occlusion of the pulmonary artery
      during balloon pulmonary valvuloplasty for pulmonary valve stenosis. MAIN OUTCOME
      MEASURES: Ventilatory tidal volume (Vt), dynamic respiratory system compliance
      (Cdyn), respiratory system resistance (Rrs). RESULTS: 28 occlusions were examined
      in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight
      patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp
      during balloon occlusion of atrial septal defect caused no significant change in
      airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61
      (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm
      H(2)O*kg; p < 0.01). These changes were more pronounced when there was complete
      cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall
      in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64
      (0.26) ml/cm H(2)O*kg; p < 0.001), and there was also an increase in Rrs (25.1
      (1. 7) to 28.8 (1.6) cm H(2)O/litre*s; p < 0.01). All these changes exceeded the
      variability of the baseline measurements more than threefold. CONCLUSIONS: Acute
      changes in pulmonary blood flow are associated with simultaneous changes in lung
      mechanics. While these changes are small they may represent a valid model to
      explain the pathophysiological impact of spontaneous changes in pulmonary blood
      flow in clinically more critical situations in children with congenital heart
      disease.

PMID- 10956290
TI  - Clinical and patho-anatomical factors affecting expansion of thoracic aortic
      aneurysms.
AB  - OBJECTIVE: To examine the expansion of aneurysmal aortic segments (> or = 35 mm)
      and to assess the impact of clinical and patho-anatomical factors on aneurysm
      expansion. DESIGN: 87 consecutive patients (mean age 63.6 years, range 22-84
      years) were studied using serial (six month intervals) computed tomographic or
      magnetic resonance imaging to monitor progression of thoracic aortic aneurysms.
      Aortic diameter was measured at seven predetermined segments and at the site of
      maximum aortic dilatation (MAX). RESULTS: 780 segment intervals were identified.
      The median overall aneurysm expansion rate was 1.43 mm/year. This increased
      exponentially with incremental aortic diameter (p < 0.01) and varied by
      anatomical segment (p < 0.05). The presence of intraluminal thrombus (p < 0.01)
      but not dissection or calcification was associated with accelerated growth.
      Univariate analysis identified thrombus (p < 0.001), previous stroke (p < 0.002),
      smoking (p < 0. 01), and peripheral vascular disease (p < 0.05) as factors
      associated with accelerated growth in MAX. Dissection, wall calcification, and
      history of hypertension did not affect expansion. beta Blocker treatment was not
      associated with protection. Multivariate analysis confirmed the positive effect
      of intraluminal thrombus and previous cerebral ischaemia, and the negative effect
      of previous aortic surgery on aneurysm growth. These findings translated into a
      mathematical equation describing exponential aneurysm expansion. CONCLUSIONS:
      Aneurysmal thoracic aortic segments expand exponentially according to their
      initial size and their anatomical position within the aorta. The presence of
      intraluminal thrombus, atherosclerosis, and smoking history is associated with
      accelerated growth and may identify a high risk patient group for close
      surveillance.

PMID- 10956293
TI  - Mechanical properties of the common carotid artery in Williams syndrome.
AB  - OBJECTIVE: To determine whether arterial wall hypertrophy in elastic arteries was
      associated with alteration in their mechanical properties in young patients with
      Williams syndrome. METHODS: Arterial pressure and intima-media thickness, cross
      sectional compliance, distensibility, circumferential wall stress, and
      incremental elastic modulus of the common carotid artery were measured non
      invasively in 21 Williams patients (mean (SD) age 8.5 (4) years) and 21 children
      of similar age. RESULTS: Systolic and diastolic blood pressures were higher in
      Williams patients (125/66 v 113/60 mm Hg, p < 0.05). The mean (SD) intima-media
      thickness was increased in Williams patients, at 0.6 (0.07) v 0.5 (0.03) mm (p <
      0. 001). Normotensive Williams patients had a lower circumferential wall stress
      (2.1 (0.5) v 3.0 (0.7) mm Hg, p < 0.01), a higher distensibility (1.1 (0.3) v 0.8
      (0.3) mm Hg(-1).10(-2), p < 0.01), similar cross sectional compliance (0.14
      (0.04) v 0.15 (0.05) mm(2). mm Hg(-1), p > 0.05), and lower incremental elastic
      modulus (7.4 (2. 0) v 14.0 (5.0) mm Hg.10(2); p < 0.001). CONCLUSIONS: The
      compliance of the large elastic arteries is not modified in Williams syndrome,
      even though increased intima-media thickness and lower arterial stiffness are
      consistent features. Therefore systemic hypertension cannot be attributed to
      impaired compliance of the arterial tree in this condition.

PMID- 10956294
TI  - Prenatal diagnosis of congenital heart disease in the northern region of England:
      benefits of a training programme for obstetric ultrasonographers.
AB  - OBJECTIVE: To examine the results of fetal cardiac scanning and audit the changes
      in performance resulting from the introduction of a training programme for
      obstetric ultrasonographers. METHODS: Using the database of the Northern Regional
      Congenital Abnormality Survey (NORCAS), fetuses with complex or significant
      congenital heart disease (CCHD) diagnosed prenatally in 1994 were identified. A
      simple programme of centralised and local training was instituted in 1995 by the
      department of paediatric cardiology to teach obstetric ultrasonographers in
      district general hospital maternity departments to identify congenital heart
      malformations. The results of the training programme were assessed by comparing
      the 1994 identification rate of CCHD with the rates for 1996 and 1997. RESULTS:
      Birth rate fell during the study from 35,026 in 1994 to 32,874 in 1997.
      Registration of CCHD also fell, from 115 in 1994 to 87 in 1997. Prenatal
      recognition of CCHD rose from 17% in 1994 to 30% in 1995 and 36% in 1996. In 1997
      it fell slightly to 26.9%. The total number of scans did not change much year on
      year, but the number of parents choosing termination increased significantly
      (from 22.7% to 57%). CONCLUSIONS: A simple training programme for obstetric
      ultrasonographers increased their ability to detect serious congenital heart
      disease at a routine 18-20 week anomaly scan. With a termination rate of more
      than 50%, the incidence of CCHD in the population fell from 3.3/1000 to 2.6/1000
      live births. This audit, conducted within a stable population using ascertainment
      by a well established fetal malformation registry, suggests that prenatal
      diagnosis may have a significant effect on the incidence of complex or serious
      congenital cardiac malformations.

PMID- 10956295
TI  - Images in cardiology: treatment of tachyarrhythmia induced syncopes by
      angioplasty of the right coronary artery.

PMID- 10956296
TI  - Influence of a history of smoking on short term (six month) clinical and
      angiographic outcome after successful coronary angioplasty.
AB  - OBJECTIVES: To assess the influence of smoking on restenosis after coronary
      angioplasty. DESIGN AND PATIENTS: The incidence of smoking on restenosis was
      investigated in 2948 patients. They were prospectively enrolled in four major
      restenosis trials in which quantitative angiography was used before and
      immediately after successful angioplasty and again at six months. RESULTS: Within
      the study population there were 530 current smokers, 1690 ex-smokers, and 728 non
      smokers. Smokers were more likely to be men (85.9% v 87. 5% v 65.3%, current v ex
      v non-, p < 0.001), to be younger (54.0 (9. 0) v 57.0 (9.1) v 59.9 (9.4) years,
      p < 0.001), to have peripheral vascular disease (7.2% v 5.5% v 2.3%, p < 0.001),
      and have sustained a previous myocardial infarction (42.9% v 43.9% v 37.9%, p =
      0.022), but were less likely to be diabetic (9.1% v 9.5% v 12.6%, p = 0.043) or
      hypertensive (24.9% v 29.3% v 37.2, p < 0.001). There was no significant
      difference in the categorical restenosis rate (> 50% diameter stenosis) at six
      months (35.28% v 35.33% v 37.09%, current v ex- v non-), or the absolute loss
      (0.29 (0.54) v 0.33 (0.52) v 0. 35 (0.55) mm, respectively; p = 0.172).
      CONCLUSIONS: Although smokers have a lower incidence of known predisposing risk
      factors for atherosclerosis, they require coronary intervention almost six years
      earlier than non-smokers and three years earlier than ex-smokers. Once they
      undergo successful coronary angioplasty, there appears to be no evidence that
      smoking influences their short term (six month) outcome, but because of the known
      long term effects of smoking, patients should still be encouraged to discontinue
      the habit.

PMID- 10956297
TI  - Clinical and angiographic outcome in patients with in-stent restenosis and repeat
      target lesion revascularisation in small coronary arteries.
AB  - OBJECTIVE: To evaluate the clinical and angiographic outcome in patients with in
      stent restenosis in small coronary arteries and repeat target lesion
      revascularisation. DESIGN: Patients with in-stent restenosis in coronary arteries
      < or = 2.85 mm were eligible for the study and underwent target lesion
      revascularisation. Clinical and angiographic variables were assessed during a six
      month follow up period. RESULTS: 73 patients with 79 lesions were treated by
      percutaneous transluminal coronary angioplasty (47%), excimer laser angioplasty
      (25%), or restenting (28%). The mean (SD) reference diameter before target lesion
      revascularisation was 2.12 (0.5) mm. Procedural success was achieved in all
      cases, but 57% of the patients had restenosis after six months. The rate of
      further restenosis was higher with laser angioplasty (78%) than with restenting
      (47%) or balloon angioplasty alone (49%, p < 0.05). CONCLUSIONS: Treatment for in
      stent restenosis in small coronary arteries is feasible and safe, with a second
      restenosis rate comparable to large coronary artery series. The strategy of
      target lesion revascularisation influences further in-stent restenosis, with an
      increased rate with laser angioplasty compared with restenting and repeat
      dilatation alone.

PMID- 10956299
TI  - Transcatheter closure of atrial septal defects using the Cardio-Seal implant.
AB  - OBJECTIVE: To review the outcomes of transcatheter closure of atrial septal
      defects using the Cardio-Seal implant. DESIGN: A prospective interventional
      study. SETTING: Tertiary referral centre. PATIENTS: The first 50 patients (median
      age 9.7 years) who underwent attempted percutaneous occlusion. INTERVENTIONS:
      Procedures were done under general anaesthesia and transoesophageal guidance
      between December 1996 and July 1998. MAIN OUTCOME MEASURES: Success of
      deployment, complications, and assessment of right ventricular end diastolic
      diameter, septal wall motion, and occlusion status by echocardiography. RESULTS:
      The median balloon stretched diameter was 14 mm. Multiple atrial septal defects
      were present in 11 patients (22%) and a deficient atrial rim (< 4 mm) in 19
      (38%). In four patients (8%), a second device was implanted after removal of an
      initially malpositioned first implant. There were no significant immediate
      complications. All patients except one were discharged within 24 hours. At the
      latest follow up (mean 9.9 months) a small shunt was present in 23 patients
      (46%), although right ventricular end diastolic dimensions (mean (SD)) corrected
      for age decreased from 137 (29)% to 105 (17)% of normal, and septal motion
      abnormalities normalised in all but one patient. No predictors for a residual
      shunt were identified. Supporting arm fractures were detected in seven patients
      (14%) and protrusion of one arm through the defect in 16 (32%), the latter being
      more common in those with smaller anterosuperior rims. No untoward effects
      resulted from arm fractures or protrusion. There were no complications during
      follow up, although five patients (10%) experienced transient headaches.
      CONCLUSIONS: The implantation of the Cardio-Seal device corrects the haemodynamic
      disturbances secondary to the right ventricular volume overload, with good early
      outcome.

PMID- 10956298
TI  - Coronary artery compliance and adaptive vessel remodelling in patients with
      stable and unstable coronary artery disease.
AB  - OBJECTIVE: To test the hypothesis that patients with unstable coronary syndromes
      show accentuated compensatory vessel enlargement compared with patients with
      stable angina, and that this may in part be related to increased coronary artery
      distensibility. DESIGN AND PATIENTS: In 23 patients with unstable coronary
      syndromes (10 with non-Q wave myocardial infarction and 13 with unstable angina),
      the culprit lesion was investigated by intravascular ultrasound before
      intervention. The vessel cross sectional area (VA), lumen area (LA), and plaque
      area (VA minus LA) were measured at end diastole and end systole at the lesion
      site and at the proximal and distal reference segments. Similar measurements were
      made in 23 patients with stable angina admitted during the same period and
      matched for age, sex, and target vessel. Calculations were made of remodelling
      index (VA at lesion site / VA at reference site), distensibility index ([(delta
      A/A)/delta P] x 10(3), where delta A is the luminal area change in systole and
      diastole and delta P the difference in systolic and diastolic blood pressure
      measured at the tip of the guiding catheter during a cardiac cycle), and
      stiffness index beta ([ln(P(sys)/P(dias))]/(delta D/D), where P(sys) is systolic
      pressure, P(dias) is diastolic pressure, and delta D is the difference between
      systolic and diastolic lumen diameters). Positive remodelling was defined as when
      the VA at the lesion was > 1.05 times larger than at the proximal reference site,
      and negative remodelling when the VA at the lesion was < 0.95 of the reference
      site. RESULTS: Mean (SD) LA at the lesion site was similar in both groups (4.03
      (1.8) v 4.01 (1. 93) mm(2)), while plaque area was larger in the unstable group
      (13. 29 (4.04) v 8.34 (3.6) mm(2), p < 0.001). Remodelling index was greater in
      the unstable group (1.14 (0.18) v 0.83 (0.15), p < 0.001). Positive remodelling
      was observed in 15 patients in the unstable group (65%) but in only two (9%) in
      the stable group (p < 0.001). Negative remodelling occurred only in two patients
      with unstable symptoms (9%) but in 17 (74%) with stable symptoms. At the proximal
      reference segment, the difference in LA between systole and diastole was 0.99
      (0.66) mm(2) in the unstable group and 0.39 (0.3) mm(2) in the stable group (p <
      0.001), and the calculated coronary artery distensibility was 3.09 (2.69) and
      0.94 (0.83) per mm Hg in unstable and stable patients, respectively (p < 0.001).
      The stiffness index beta was lower in patients with unstable angina (1.95 (0.94)
      v 3.1 (0.96), p < 0.001). CONCLUSIONS: Compensatory vessel enlargement occurs to
      a greater degree in patients with unstable than with stable coronary syndromes,
      and is associated with increased coronary artery distensibility.

PMID- 10956300
TI  - Morphology of perforated atrial septal aneurysm suitable for closure by
      transcatheter device placement.
AB  - OBJECTIVE: To define the morphological criteria of perforated atrial septal
      aneurysms suitable for closure by a transcatheter device. METHODS: A
      retrospective analysis of all consecutive patients with atrial septal aneurysm
      and one or more perforations presenting between May 1997 and June 1999. The
      aneurysms were classified as: aneurysm with persistent foramen ovale (type A);
      aneurysm with single atrial septal defect (type B); aneurysm with two
      perforations requiring more than one device for closure (type C); and aneurysm
      with multiple perforations (type D). PATIENTS: Data from 50 patients aged 5-78
      years (mean 43 years) were analysed; 32 had systemic thromboembolism or transient
      ischaemic attacks, eight presented with dyspnoea on exercise, and 10 were
      discovered incidentally but had significant left to right shunt and right
      ventricular volume overload. RESULTS: In all 18 patients with aneurysm and
      persistent foramen ovale (type A), transcatheter closure was possible. In nine
      with aneurysm and atrial septal defect (type B), five defects were closed and
      four required surgery. Device closure was achieved in all 10 patients with
      aneurysms and two perforations (type C), but four had a residual shunt. Thirteen
      patients with multiple perforated aneurysms (type D) underwent surgery.
      CONCLUSIONS: This classification of morphology of perforations of aneurysm is
      clinically useful for selecting patients for treatment by transcatheter devices.

PMID- 10956302
TI  - Images in cardiology: biventricular diverticula in a patient with restrictive
      cardiomyopathy.

PMID- 10956301
TI  - Regional myocardial wall thickening assessed at rest by ECG gated (18)F-FDG
      positron emission tomography and by magnetic resonance imaging.

PMID- 10956303
TI  - The diagnosis of heart failure.

PMID- 10956304
TI  - Antiarrhythmic drugs: from mechanisms to clinical practice.

PMID- 10956305
TI  - Interface between valve disease and ischaemic heart disease.

PMID- 10956306
TI  - Pressure damping, a "billowing" septum, and an eerie silence: perioperative,
      intermittent obstruction of a mitral valve prosthesis.
AB  - This case, involving a 74 year old man who underwent mitral valve and aortic
      valve replacements, provides detailed insight into the perioperative
      echocardiographic and haemodynamic changes occurring when a mitral valve
      prosthesis intermittently obstructs. It illustrates the early sequence of
      electromechanical dissociation which would lead to cardiac arrest should a
      tilting disc prosthesis be immobilised in the closed position.

PMID- 10956307
TI  - Coexistence of giant aneurysm of sinus of Valsalva and coronary artery aneurysm
      associated with idiopathic hypereosinophilic syndrome.
AB  - Aneurysms of the coronary sinuses of Valsalva and coronary artery aneurysms are
      uncommon cardiac anomalies, and cases in which these two uncommon lesions occur
      at the same time are extremely rare. A case of a woman with unstable angina who
      had a giant aneurysm of the left coronary sinus and multiple coronary artery
      aneurysms associated with an idiopathic hypereosinophilic syndrome is presented.
      Her sustained eosinophilia, elevated eosinophilic cationic protein concentration,
      and pathological findings of eosinophil infiltration of the aortic wall suggested
      the association of eosinophilia induced vascular injury as the cause of these
      aneurysms. This is the first such case to survive following surgical treatment.

PMID- 10956308
TI  - Renin-angiotensin system modulating treatments in the management of
      cardiovascular disease.

PMID- 10956309
TI  - STOP-Hypertension-2 and best practice for the future.

PMID- 10956310
TI  - Secondary prevention: improving outcomes following myocardial infarction.

PMID- 10956311
TI  - Improving patient outcomes in heart failure: evidence and barriers.

PMID- 10956312
TI  - Angiotensin converting enzyme inhibition: from viper to patient.

PMID- 10956313
TI  - Left ventricular dysfunction: causes, natural history, and hopes for reversal.

PMID- 10956314
TI  - Renin-angiotensin system mediated mechanisms: cardioreparation and
      cardioprotection.

PMID- 10956315
TI  - Endothelial dysfunction: the role and impact of the renin-angiotensin system.

PMID- 10956317
TI  - Diabetic nephropathy: evidence for renoprotection and practice.

PMID- 10956316
TI  - Managing cardiovascular risk in patients with diabetes.

PMID- 10956318
TI  - Modulation of the renin-angiotensin system and retinopathy.

PMID- 10956319
TI  - RAS blockade: new possibilities in the treatment of complications of diabetes.

PMID- 10956320
TI  - Modern management of hypertension and heart failure: evidence and practice.

PMID- 10956321
TI  - ACE inhibition and AT(1) receptor blockers: efficacy and duration in
      hypertension.

PMID- 10956322
TI  - AT(1) receptor antagonists-beyond blood pressure control: possible place in heart
      failure treatment.

PMID- 10956323
TI  - Lipid lowering: statins and the future.

PMID- 10956324
TI  - The future: cardiovascular medicine in 10 years.

PMID- 10956326
TI  - The "impact factor": what it means to the impact of applied physiology

PMID- 10956327
TI  - The new kid on the airway smooth muscle block: plasticity theory and series-to
      parallel filament transition.

PMID- 10956328
TI  - Series-to-parallel transition in the filament lattice of airway smooth muscle.
AB  - Force-velocity curves measured at different times during tetani of sheep
      trachealis muscle were analyzed to assess whether velocity slowing could be
      explained by thick-filament lengthening. Such lengthening increases force by
      placing more cross bridges in parallel on longer filaments and decreases velocity
      by reducing the number of filaments spanning muscle length. From 2 s after the
      onset of stimulation, when force had achieved 42% of it final value, to 28 s,
      when force had been at its tetanic plateau for approximately 15 s, velocity
      decreases were exactly matched by force increases when force was adjusted for
      changes in activation, as assessed from the maximum power value in the force
      velocity curves. A twofold change in velocity could be quantitatively explained
      by a series-to-parallel change in the filament lattice without any need to
      postulate a change in cross-bridge cycling rate.

PMID- 10956329
TI  - Postprandial increases in serum antioxidant capacity in older women.
AB  - Eight women were recruited for studying the effects of a meal on overall
      antioxidant status. Subjects resided in a metabolic research unit for two 36-h
      periods. During period A, subjects fasted overnight (12 h) and were then given a
      breakfast, a lunch, a snack, and a dinner. During period B, subjects fasted for
      23 h and were then given a dinner. These meals were designed to contain
      negligible antioxidants. Blood samples were collected for analyzing total
      antioxidant capacity (TAC) and individual antioxidants. The results showed that
      serum TAC significantly increased by up to 23% after the consumption of the lunch
      and dinner during period A. Serum TAC did not increase until after the
      consumption of the dinner during period B. Among the antioxidants (vitamin C,
      alpha-tocopherol, bilirubin, and uric acid) examined, serum uric acid was the
      only one that showed a significant postprandial increase, which was also parallel
      to the postprandial response in serum TAC. These results indicate that food
      intake, even if low in antioxidants, can increase the serum total antioxidant
      activity.

PMID- 10956330
TI  - Effect of budesonide and salbutamol on surfactant properties.
AB  - The objective of this study was to evaluate the in vitro effect of budesonide and
      salbutamol on the surfactant biophysical properties. The surface-tension
      properties of two bovine lipid extracts [bovine lipid extract surfactant (BLES)
      and Survanta] and a rat lung lavage natural surfactant were evaluated in vitro by
      the captive bubble surfactometer. Measurements were obtained before and after the
      addition of a low and high concentration of budesonide and salbutamol. Whereas
      salbutamol had no significant effect, budesonide markedly reduced the surface
      tension-lowering properties of all surfactant preparations. Surfactant adsorption
      (decrease in surface tension vs. time) was significantly reduced (P < 0.01) at a
      high budesonide concentration with BLES, both concentrations with Survanta, and a
      low concentration with natural surfactant. At both concentrations, budesonide
      reduced (P < 0.01) Survanta film stability (minimal surface vs. time at minimum
      bubble volume), whereas no changes were seen with BLES. The minimal surface
      tension obtained for all surfactant preparations was significantly higher (P <
      0.01), and the percentage of film area compression required to reach minimum
      surface tension was significantly lower after the addition of budesonide. In
      conclusion, budesonide, at concentrations used therapeutically, adversely affects
      the surface-tension-lowering properties of surfactant. We speculate that it may
      have the same adverse effect on the human surfactant.

PMID- 10956331
TI  - Effects of fatigue on sarcoplasmic reticulum and myofibrillar properties of rat
      single muscle fibers.
AB  - Force decline during fatigue in skeletal muscle is attributed mainly to
      progressive alterations of the intracellular milieu. Metabolite changes and the
      decline in free myoplasmic calcium influence the activation and contractile
      processes. This study was aimed at evaluating whether fatigue also causes
      persistent modifications of key myofibrillar and sarcoplasmic reticulum (SR)
      proteins that contribute to tension reduction. The presence of such modifications
      was investigated in chemically skinned fibers, a procedure that replaces the
      fatigued cytoplasm from the muscle fiber with a normal medium. Myofibrillar
      Ca(2+) sensitivity was reduced in slow-twitch muscle (for example, the pCa value
      corresponding to 50% of maximum tension was 6.23 +/- 0.03 vs. 5.99 + 0.05, P <
      0.01, in rested and fatigued fibers) and not modified in fast-twitch muscle.
      Phosphorylation of the regulatory myosin light chain isoform increased in fast
      twitch muscle. The rate of SR Ca(2+) uptake was increased in slow-twitch muscle
      fibers (14.2 +/- 1.0 vs. 19.6 +/- 2. 5 nmol. min(-1). mg fiber protein(-1), P <
      0.05) and not altered in fast-twitch fibers. No persistent modifications of SR
      Ca(2+) release properties were found. These results indicate that persistent
      modifications of myofibrillar and SR properties contribute to fatigue-induced
      muscle force decline only in slow fibers. These alterations may be either
      enhanced or counteracted, in vivo, by the metabolic changes that normally occur
      during fatigue development.

PMID- 10956332
TI  - Oxygen uptake kinetics in treadmill running and cycle ergometry: a comparison.
AB  - The purpose of the present study was to comprehensively examine oxygen
      consumption (VO(2)) kinetics during running and cycling through mathematical
      modeling of the breath-by-breath gas exchange responses to moderate and heavy
      exercise. After determination of the lactate threshold (LT) and maximal oxygen
      consumption (VO(2 max)) in both cycling and running exercise, seven subjects (age
      26.6 +/- 5.1 yr) completed a series of "square-wave" rest-to-exercise transitions
      at running speeds and cycling power outputs that corresponded to 80% LT and 25,
      50, and 75%Delta (Delta being the difference between LT and VO(2 max)). VO(2)
      responses were fit with either a two- (<LT) or three-phase ( >LT) exponential
      model. The parameters of the VO(2) kinetic response were similar between exercise
      modes, except for the VO(2) slow component, which was significantly (P < 0.05)
      greater for cycling than for running at 50 and 75%Delta (334 +/- 183 and 430 +/-
      159 ml/min vs. 205 +/- 84 and 302 +/- 154 ml/min, respectively). We speculate
      that the differences between the modes are related to the higher intramuscular
      tension development in heavy cycle exercise and the higher eccentric exercise
      component in running. This may cause a relatively greater recruitment of the less
      efficient type II muscle fibers in cycling.

PMID- 10956333
TI  - Comparative respiratory system mechanics in rodents.
AB  - Because of the wide utilization of rodents as animal models in respiratory
      research and the limited data on measurements of respiratory input impedance
      (Zrs) in small animals, we measured Zrs between 0.25 and 9.125 Hz at different
      levels (0-7 hPa) of positive end-expiratory pressure (PEEP) in mice, rats, guinea
      pigs, and rabbits using a computer-controlled small-animal ventilator (Schuessler
      TF and Bates JHT, IEEE Trans Biomed Eng 42: 860-866, 1995). Zrs was fitted with a
      model, including a Newtonian resistance (R) and inertance in series with a
      constant-phase tissue compartment characterized by tissue damping (Gti) and
      elastance (Hti) parameters. Inertance was negligible in all cases. R, Gti, and
      Hti were normalized to body weight, yielding normalized R, Gti, and Hti (NHti),
      respectively. Normalized R tended to decrease slightly with PEEP and increased
      with animal size. Normalized Gti had a minimal dependence on PEEP. NHti decreased
      with increasing PEEP, reaching a minimum at approximately 5 hPa in all species
      except mice. NHti was also higher in mice and rabbits compared with guinea pigs
      and rats at low PEEPs, which we conclude is probably due to a relatively smaller
      air space volume in mice and rabbits. Our data also suggest that smaller rodents
      have proportionately wider airways than do larger animals. We conclude that a
      detailed, comparative study of respiratory system mechanics shows some evidence
      of structural differences among the lungs of various species but that, in
      general, rodent lungs obey scaling laws similar to those described in other
      species.

PMID- 10956334
TI  - Respiratory neuronal activity during apnea and poststimulatory effects of
      laryngeal origin in the cat.
AB  - We investigated the behavior of medullary respiratory neurons in cats under
      pentobarbitone anesthesia, vagotomized, paralysed, and artificially ventilated to
      elucidate neural mechanisms underlying apnea and poststimulatory respiratory
      depression induced by superior laryngeal nerve (SLN) stimulation. Inspiratory
      neurons were completely inhibited during SLN stimulation and poststimulatory
      apnea. During recovery of inspiratory activity, augmenting inspiratory neurons
      were depressed, decrementing inspiratory neurons were excited, and late
      inspiratory neurons displayed unchanged bursts closely locked to the end of the
      inspiratory phase. Augmenting expiratory neurons were either silenced or
      displayed different levels of tonic activity during SLN stimulation; some of them
      were clearly activated. These expiratory neurons displayed activity during
      poststimulatory apnea, before the onset of the first recovery phrenic burst.
      Postinspiratory or decrementing expiratory neurons were activated during SLN
      stimulation; their discharge continued with a decreasing trend during
      poststimulatory apnea. The results support the three-phase theory of rhythm
      generation and the view that SLN stimulation provokes a postinspiratory apnea
      that could represent the inhibitory component of respiratory reflexes of
      laryngeal origin, such as swallowing. In addition, because a subpopulation of
      augmenting expiratory neurons displays activation during SLN stimulation, the
      hypothesis can be advanced that not only postinspiratory, or decrementing
      expiratory neurons, but also augmenting expiratory neurons may be involved in the
      genesis of apnea and poststimulatory phenomena. Finally, the increase in the
      activity of decrementing inspiratory neurons after the end of SLN stimulation may
      contribute to the generation of poststimulatory respiratory depression by
      providing an inhibitory input to bulbospinal augmenting inspiratory neurons.

PMID- 10956335
TI  - Activation of human quadriceps femoris muscle during dynamic contractions:
      effects of load on fatigue.
AB  - Muscle fatigue is both multifactorial and task dependent. Electrical stimulation
      may assist individuals with paralysis to perform functional activities
      [functional electrical stimulation (FES), e.g., standing or walking], but muscle
      fatigue is a limiting factor. One method of optimizing force is to use
      stimulation patterns that exploit the catchlike property of skeletal muscle
      [catchlike-inducing trains (CITs)]. Although nonisometric (dynamic) contractions
      are important parts of both normal physiological activation of skeletal muscles
      and FES, no previous studies have attempted to identify the effect that the load
      being lifted by a muscle has on the fatigue produced. This study examined the
      effects of load on fatigue during dynamic contractions and the augmentation
      produced by CITs as a function of load. Knee extension in healthy subjects was
      electrically elicited against three different loads. The highest load produced
      the least excursion, work, and average power, but it produced the greatest
      fatigue. CIT augmentation was greatest at the highest load and increased with
      fatigue. Because CITs were effective during shortening contractions for a variety
      of loads, they may be of benefit during FES applications.

PMID- 10956336
TI  - Catecholamine release, growth hormone secretion, and energy expenditure during
      exercise vs. recovery in men.
AB  - We examined the relationship between energy expenditure (in kcal) and epinephrine
      (Epi), norepinephrine (NE), and growth hormone (GH) release. Ten men [age, 26 yr;
      height, 178 cm; weight, 81 kg; O(2) uptake at lactate threshold (LT), 36.3 ml.
      kg(-1). min(-1); peak O(2) uptake, 49.5 ml. kg(-1). min(-1)] were tested on six
      randomly ordered occasions [control, 5 exercise: at 25 and 75% of the difference
      between LT and rest (0.25LT, 0.75LT), at LT, and at 25 and 75% of the difference
      between LT and peak (1.25LT, 1.75LT) (0900-0930)]. From 0700 to 1300, blood was
      sampled and assayed for GH, Epi, and NE. Carbohydrate (CHO) expenditure during
      exercise and fat expenditure during recovery rose proportionately to increasing
      exercise intensity (P = 0.002). Fat expenditure during exercise and CHO
      expenditure during recovery were not affected by exercise intensity. The
      relationship between exercise intensity and CHO expenditure during exercise could
      not be explained by either Epi (P = 1.00) or NE (P = 0.922), whereas fat
      expenditure during recovery increased with Epi and GH independently of exercise
      intensity (P = 0. 028). When Epi and GH were regressed against fat expenditure
      during recovery, only GH remained statistically significant (P < 0.05). We
      conclude that a positive relationship exists between exercise intensity and both
      CHO expenditure during exercise and fat expenditure during recovery and that the
      increase in fat expenditure during recovery with higher exercise intensities is
      related to GH release.

PMID- 10956337
TI  - Blood pressure and heart rate during periodic breathing while asleep at high
      altitude.
AB  - The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia
      during wakefulness progressively increased in normal subjects staying 4 wk at
      5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno
      V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724-1730, 1996). In the same
      subjects (n = 5, age 28-34 yr) and expedition, nocturnal polysomnography with ABP
      and heart rate (HR) recordings were obtained during the 1st and 4th week to study
      the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs.
      tonic (i. e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR
      fluctuated during non-rapid eye movement sleep periodic breathing. None of the
      subjects exhibited an ABP increase during the ventilatory phases that correlated
      with the lowest arterial oxygen saturation of the preceding pauses. Despite
      attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were
      similar to those in the 1st wk. Because ABP during periodic breathing in the
      ventilatory phase increased similarly to the ABP response to progressive hypoxia
      during wakefulness, ABP variations during ventilatory phases may reflect ABP
      responsiveness to peripheral chemoreflex sensitivity rather than the absolute
      value of hypoxemia, suggesting a major tonic effect of hypoxia on
      cardiorespiratory control at high altitude.

PMID- 10956338
TI  - Airway closure with high PEEP in vivo.
AB  - When airway smooth muscle is contracted in vitro, the airway lumen continues to
      narrow with increasing concentrations of agonist until complete airway closure
      occurs. Although there remains some controversy regarding whether airways can
      close in vivo, recent work has clearly demonstrated that, if the airway is
      sufficiently stimulated with contractile agonists, complete closure of even large
      cartilaginous conducting airways can readily occur with the lung at functional
      residual capacity (Brown RH and Mitzner W. J Appl Physiol 85: 2012-2017, 1998).
      This result suggests that the tethering of airways in situ by parenchymal
      attachments is small at functional residual capacity. However, at lung volumes
      above functional residual capacity, the outward tethering of airways should
      increase, because both the parenchymal shear modulus and tethering forces
      increase in proportion to the transpulmonary pressure. In the present study, we
      tested whether we could prevent airway closure in vivo by increasing lung volume
      with positive end-expiratory pressure (PEEP). Airway smooth muscle was stimulated
      with increasing methacholine doses delivered directly to airway smooth muscle at
      three levels of PEEP (0, 6, and 10 cmH(2)O). Our results show that increased lung
      volume shifted the airway methacholine dose-response curve to the right, but, in
      many airways in most animals, airway closure still occurred even at the highest
      levels of PEEP.

PMID- 10956339
TI  - Analysis of ultrasonically extracted interstitial fluid as a predictor of blood
      glucose levels.
AB  - Transdermal extraction of clinically relevant analytes offers a potentially
      noninvasive method of diagnostics. However, development of such a method is
      limited by the low permeability of skin. In this paper, we present a potential
      method for noninvasive diagnostics based on ultrasonic skin permeabilization and
      subsequent extraction of interstitial fluid (ISF) across the skin using vacuum.
      ISF extracted by this method was collected and analyzed for glucose and other
      analytes. Glucose concentration in the extracted fluid correlates well with blood
      glucose concentration over a range of 50-250 mg/dl. A mathematical model
      describing vacuum-induced transport of ISF through ultrasonically permeabilized
      skin is presented as well. The model accounts for convective, as well as
      diffusive, transport processes across blood capillaries, epidermis, and the
      stratum corneum. The overall predictions of the model compare favorably with the
      experimental observations.

PMID- 10956340
TI  - Changes in intra-abdominal pressure during postural and respiratory activation of
      the human diaphragm.
AB  - In humans, when the stability of the trunk is challenged in a controlled manner
      by repetitive movement of a limb, activity of the diaphragm becomes tonic but is
      also modulated at the frequency of limb movement. In addition, the tonic activity
      is modulated by respiration. This study investigated the mechanical output of
      these components of diaphragm activity. Recordings were made of costal diaphragm,
      abdominal, and erector spinae muscle electromyographic activity; intra-abdominal,
      intrathoracic, and transdiaphragmatic pressures; and motion of the rib cage,
      abdomen, and arm. During limb movement the diaphragm and transversus abdominis
      were tonically active with added phasic modulation at the frequencies of both
      respiration and limb movement. Activity of the other trunk muscles was not
      modulated by respiration. Intra-abdominal pressure was increased during the
      period of limb movement in proportion to the reactive forces from the movement.
      These results show that coactivation of the diaphragm and abdominal muscles
      causes a sustained increase in intra-abdominal pressure, whereas inspiration and
      expiration are controlled by opposing activity of the diaphragm and abdominal
      muscles to vary the shape of the pressurized abdominal cavity.

PMID- 10956341
TI  - Resistance training increases total energy expenditure and free-living physical
      activity in older adults.
AB  - The purpose of this study was to determine what effects 26 wk of resistance
      training have on resting energy expenditure (REE), total free-living energy
      expenditure (TEE), activity-related energy expenditure (AEE), engagement in free
      living physical activity as measured by the activity-related time equivalent
      (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men (n =
      8) and women (n = 7). Before and after training, body composition (four
      compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE - REE +
      thermic response to meals), and ARTE (AEE adjusted for energy cost of standard
      activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly
      increased, but body weight did not change. REE increased 6.8%, whereas resting
      RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased
      significantly, and AEE (30%) approached significance (P = 0.06). The TEE increase
      remained significant even after adjustment for the energy expenditure of the
      resistance training. In response to resistance training, TEE increased and RER
      decreased. The increase in TEE occurred as a result of increases in both REE and
      physical activity. These results suggest that resistance training may have value
      in increasing energy expenditure and lipid oxidation rates in older adults,
      thereby improving their metabolic profiles.

PMID- 10956342
TI  - On-line monitoring of intrinsic PEEP in ventilator-dependent patients.
AB  - Measurement of the intrinsic positive end-expiratory pressure (PEEP(i)) is
      important in planning the management of ventilated patients. Here, a new
      recursive least squares method for on-line monitoring of PEEP(i) is proposed for
      mechanically ventilated patients. The procedure is based on the first-order model
      of respiratory mechanics applied to experimental measurements obtained from eight
      ventilator-dependent patients ventilated with four different ventilatory modes.
      The model PEEP(i) (PEEP(i,mod)) was recursively constructed on an inspiration-by
      inspiration basis. The results were compared with two well-established techniques
      to assess PEEP(i): end-expiratory occlusion to measure static PEEP(i) (PEEP(i,
      st)) and change in airway pressure preceding the onset of inspiratory airflow to
      measure dynamic PEEP(i) (PEEP(i,dyn)). PEEP(i, mod) was significantly correlated
      with both PEEP(i,dyn) (r = 0.77) and PEEP(i,st) (r = 0.90). PEEP(i,mod) (5.6 +/-
      3.4 cmH(2)O) was systematically >PEEP(i,dyn) and PEEP(i,st) (2.7 +/- 1.9 and 8.1
      +/- 5.5 cmH(2)O, respectively), in all the models without external PEEP. Focusing
      on the five patients with chronic obstructive pulmonary disease, PEEP(i,mod) was
      significantly correlated with PEEP(i,st) (r = 0.71), whereas PEEP(i,dyn) (r =
      0.22) was not. When PEEP was set 5 cmH(2)O above PEEP(i,st), all the methods
      correctly estimated total PEEP, i.e., 11.8 +/- 5.3, 12.5 +/- 5.0, and 12.0 +/-
      4.7 cmH(2)O for PEEP(i,mod), PEEP(i,st), and PEEP(i,dyn), respectively, and were
      highly correlated (0.97-0.99). We interpreted PEEP(i,mod) as the lower bound of
      PEEP(i,st) and concluded that our method is suitable for on-line monitoring of
      PEEP(i) in mechanically ventilated patients.

PMID- 10956344
TI  - Dual effects of nitric oxide on cat carotid body chemoreception.
AB  - We studied the effects of nitric oxide (NO) released by NO donors on cat carotid
      body (CB) chemosensory activity during normoxia and hypoxia. CBs excised from
      pentobarbital sodium-anaesthetized cats were perfused with Tyrode at 38 degrees C
      and pH 7.40. The frequency of chemosensory discharges (f(x)) was recorded from
      the carotid sinus nerve, and changes of NO concentration were measured by a
      chronoamperometric technique, with NO-selective carbon-fiber microelectrodes
      inserted in the CB. During steady chemosensory excitation induced by hypoxia,
      bolus injections of NO (DeltaNO = 0. 5-12 microM), released by S-nitroso-N
      acetylpenicillamine (SNAP) and 6-(2-hydroxy-1-methyl-nitrosohydrazino)-N-methyl-1
      hexanamine++ + (NOC-9), transiently reduced f(x) in a dose-dependent manner.
      However, during normoxia, the same concentration of NO (DeltaNO = 0. 5-13 microM)
      released by the NO donors increased f(x) in a dose-dependent manner. The present
      results show a dual effect of NO on CB chemoreception that is dependent on the
      PO(2) levels. During hypoxia, NO is predominantly an inhibitor of chemoreception,
      whereas, in normoxia, NO increased f(x). The mechanisms by which NO produces
      chemosensory excitation during normoxia remain to be determined.

PMID- 10956343
TI  - Modulation of respiratory motor output by cerebellar deep nuclei in the rat.
AB  - The present study was undertaken to determine what roles the various cerebellar
      deep nuclei (CDN) play in modulation of respiration, especially during chemical
      challenges. Experiments were carried out in 12 anesthetized, tracheotomized,
      paralyzed, and ventilated rats. The integrated phrenic nerve activity
      (integralPN) was recorded as an index of respiratory motor output. A stimulating
      electrode was sequentially placed into the fastigial nucleus (FN), the interposed
      nucleus, and the lateral nucleus. Only stimulation of the FN significantly
      altered respiration, primarily via increasing respiratory frequency associated
      with a pressor response. The evoked respiratory responses persisted after
      blocking the pressor response via pretreatment with phenoxybenzamine or use of
      transient stimulation (<2 s) but were abolished by microinjection of kainic acid
      into the FN. To test the involvement of FN neurons in respiratory chemoreflexes,
      ventilation with hypercapnic gases mixture and intravenous injection of sodium
      cyanide were applied before and after CDN lesions induced by kainic acid. CDN
      lesions did not significantly alter eupneic breathing, but FN lesions attenuated
      the respiratory response to hypercapnia and sodium cyanide. We conclude that,
      with respect to the CDN in the rat, FN neurons uniquely modulate respiration
      independent of cardiovascular effects and facilitate respiratory responses
      mediated by activation of CO(2) and O(2) receptors.

PMID- 10956345
TI  - Acoustic rhinometry: validation by three-dimensionally reconstructed computer
      tomographic scans.
AB  - The aim of the present study was a validation of acoustic rhinometry (AR) by
      computed tomography (CT). Six healthy subjects were examined by CT and AR. The CT
      data were processed in a computer program (AutoCAD), and a virtual three
      dimensional model of each nasal cavity was constructed. This model permitted an
      individual prediction of the center line of the sound wave propagation through
      the air volume of the nasal cavity with the cross-sectional areas oriented
      perpendicularly to this line. The area-distance curves derived from AR and CT
      were compared. Linear regression analysis revealed a reasonable agreement of AR
      and CT in the anterior nose below a mean of 6 cm distance from the nostrils [r =
      0.839, P < 0.01, m = 1.123, b = -0.113 (AR = m x CT + b)]. The measuring accuracy
      using CT as gold standard revealed a mean error at the nasal valve of <0.01 cm(2)
      (4.52%) and at the nasal isthmus of 0.02 cm(2) (1. 87%). Beyond 6 cm, the
      correlation decreased (r = 0.419), and overestimation of the true area occurred
      (>100%). In conclusion, the measurements were reasonably accurate for diagnostic
      use up to the turbinate head region. Certain factors induce an overestimation of
      the true areas beyond this region. However, these factors are constant and
      reproducible in a single subject, and intraindividual comparative measurements
      are possible beyond the turbinate head region.

PMID- 10956346
TI  - Constraints on cardiac hypertrophy imposed by myocardial viscosity.
AB  - Laplace's law constrains how thin the ventricular wall may be without
      experiencing excessive stress. The present study investigated constraints,
      imposed by myocardial viscosity (resistance to internal rearrangement), on how
      thick the wall may be. The ventricle was modeled as a contracting, spherical
      shell. The analysis demonstrated that viscosity generates stress and energy
      dissipation with inverse fourth- and eighth-power dependence, respectively, on
      distance from the cavity center. This result derives from the combination of
      squared dependence of viscous forces on shearing velocity gradients and the
      greater shear rearrangement required for inner layers of a contracting sphere.
      These predictions are based solely on geometry and fundamentals of viscosity and
      are independent of material properties, cytoskeletal structure, and internal
      structural forces. Calculated values of energy and force required to overcome
      viscosity were clearly large enough to affect the extent of thickening of the
      left ventricle. It is concluded that load-independent viscous resistance to
      contraction is an important factor in cardiac mechanics, especially of the
      thickened ventricles of concentric hypertrophy.

PMID- 10956347
TI  - Endurance training does not alter the level of neuronal nitric oxide synthase in
      human skeletal muscle.
AB  - The effect of endurance training on neuronal nitric oxide synthase (nNOS) content
      and distribution in muscle was investigated. Seven male subjects performed 6 wk
      of one-legged knee-extensor endurance training (protocol A). Muscle biopsies,
      obtained from vastus lateralis muscle in the untrained and the trained leg, were
      analyzed for nNOS protein and activity as well as immunohistochemical
      distribution of nNOS and endothelial nitric oxide synthase (eNOS). Muscle
      biopsies were also obtained from another seven male subjects before and after 6
      wk of training by endurance running (protocol B) and analyzed for nNOS protein.
      No difference was found in the amount of nNOS protein in the untrained and the
      trained muscle either with protocol A or protocol B (P > 0.05). In protocol A,
      the activity of nNOS was 4.76 +/- 0.56 pmol. mg protein(-1). min(-1) in the
      control leg, and the level was not different in the trained leg (P > 0.05). nNOS
      was present in the sarcolemma and cytosol of type I and type II muscle fibers,
      and the qualitative distribution was similar in untrained and trained muscle. The
      number of eNOS immunoreactive structures and the number of capillaries per muscle
      fiber were higher (P < 0.05) after training than before. The present findings
      demonstrate that, in contrast to findings on animals, nNOS levels remain
      unaltered with endurance training in humans. Evidence is also provided that
      endurance training may increase the amount of eNOS, in parallel with an increase
      in capillaries in human muscle.

PMID- 10956348
TI  - Nine months in space: effects on human autonomic cardiovascular regulation.
AB  - We studied three Russian cosmonauts to better understand how long-term exposure
      to microgravity affects autonomic cardiovascular control. We recorded the
      electrocardiogram, finger photoplethysmographic pressure, and respiratory flow
      before, during, and after two 9-mo missions to the Russian space station Mir.
      Measurements were made during four modes of breathing: 1) uncontrolled
      spontaneous breathing; 2) stepwise breathing at six different frequencies; 3)
      fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R
      R) interval standard deviations decreased in all and respiratory frequency R-R
      interval spectral power decreased in two cosmonauts in space. Two weeks after the
      cosmonauts returned to Earth, R-R interval spectral power was decreased, and
      systolic pressure spectral power was increased in all. The transfer function
      between systolic pressures and R-R intervals was reduced in-flight, was reduced
      further the day after landing, and had not returned to preflight levels by 14
      days after landing. Our results suggest that long-duration spaceflight reduces
      vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these
      changes may persist as long as 2 wk after return to Earth.

PMID- 10956349
TI  - Alterations in skeletal perfusion with simulated microgravity: a possible
      mechanism for bone remodeling.
AB  - Bone loss occurs as a consequence of exposure to microgravity. Using the hindlimb
      unloaded rat to model spaceflight, this study had as its purpose to determine
      whether skeletal unloading and cephalic fluid shifts alter bone blood flow. We
      hypothesized that perfusion would be diminished in the hindlimb bones and
      increased in skeletal structures of the forelimbs and head. Using radiolabeled
      microspheres, we measured skeletal perfusion during control standing and after 10
      min, 7 days, and 28 days of hindlimb unloading (HU). Femoral and tibial perfusion
      were reduced with 10 min of HU, and blood flow to the femoral shaft and marrow
      were further diminished with 28 days of HU. Correspondingly, the mass of femora (
      11%, P < 0. 05) and tibiae (-6%, P < 0.1) was lowered with 28 days of HU. In
      contrast, blood flow to the skull, mandible, clavicle, and humerus was increased
      with 10 min HU but returned to control levels with 7 days HU. Mandibular (+10%, P
      < 0.05), clavicular (+18%, P < 0.05), and humeral (+8%, P < 0.1) mass was
      increased with chronic HU. The data demonstrate that simulated microgravity
      alters bone perfusion and that such alterations correspond to unloading-induced
      changes in bone mass. These results support the hypothesis that alterations in
      bone blood flow provide a stimulus for bone remodeling during periods of
      microgravity.

PMID- 10956350
TI  - HSP72 gene expression progressively increases in human skeletal muscle during
      prolonged, exhaustive exercise.
AB  - To examine the effect of exercise on heat shock protein (HSP) 72 mRNA expression
      in skeletal muscle, five healthy humans (20 +/- 1 yr; 64 +/- 3 kg; peak O(2)
      uptake of 2.55 +/- 0.2 l/min) cycled until exhaustion at a workload corresponding
      to 63% peak O(2) uptake. Muscle was sampled from the vastus lateralis, and muscle
      temperature was measured at rest (R), 10 min of exercise (Min10), approximately
      40 min before fatigue (F-40 = 144 +/- 7 min), and fatigue (F = 186 +/- 15 min).
      Muscle samples were analyzed for HSP72 mRNA expression, as well as glycogen and
      lactate concentration. Muscle temperature increased (P < 0.05) during the first
      10 min of exercise but then remained constant for the duration of the exercise.
      Similarly, lactate concentration increased (P < 0.05) when Min10 was compared
      with R but decreased (P < 0.05) thereafter, such that concentrations at F-40 and
      F were not different from those at R. In contrast, muscle glycogen concentration
      fell progressively throughout exercise (486 +/- 74 vs. 25 +/- 7 mmol/kg dry
      weight for R and F, respectively; P < 0.05). HSP72 mRNA was detected at R but did
      not increase by Min10. However, HSP72 mRNA increased (P < 0.05) 2.2 +/- 0.5- and
      2.6 +/- 0.9-fold, respectively, when F-40 and F were compared with R. These data
      demonstrate that HSP72 mRNA increases progressively during acute cycling,
      suggesting that processes that take place throughout concentric exercise are
      capable of initiating a stress response.

PMID- 10956351
TI  - Gender- and height-related limits of muscle strength in world weightlifting
      champions.
AB  - To assess factors that limit human muscle strength and growth, we examined the
      relationship between performance and body dimensions in the world weightlifting
      champions of 1993-1997. Weight lifted varied almost exactly with height squared
      (Ht(2.16)), suggesting that muscle mass scaled almost exactly with height cubed
      (Ht(3.16)) and that muscle cross-sectional area was closely correlated with body
      height, possibly because height and the numbers of muscle fibers in cross section
      are determined by a common factor during maturation. Further height limitations
      of muscle strength were shown by only one male champion >/=183 cm and no female
      champions >/=175 cm. The ratio of weight lifted to mean body cross-sectional area
      was approximately constant for body-weight classes </=83 kg for men and </=64 kg
      for women and decreased abruptly for higher weight classes. These findings
      suggest a nearly constant fraction of body mass devoted to muscle in lighter
      lifters and a lesser fraction in heavier lifters. Analysis also suggests that
      contractile tissue comprises approximately 30% less body mass in female
      champions.

PMID- 10956352
TI  - Adaptation of laser-Doppler flowmetry to measure cerebral blood flow in the fetal
      sheep.
AB  - The purpose of this study was to devise a means to use laser-Doppler flowmetry to
      measure cerebral perfusion before birth. The method has not been used previously,
      largely because of intrauterine movement artifacts. To minimize movement
      artifacts, a probe holder was molded from epoxy putty to the contour of the fetal
      skull. A curved 18-gauge needle was embedded in the holder. At surgery, the
      holder, probe, and skull were fixed together with tissue glue. Residual signals
      were recorded after fetal death and after maternal death 1 h later. These
      averaged <5% of baseline flow signals, indicating minimal movement artifact. To
      test the usefulness of the method, cerebral flow responses were measured during
      moderate fetal hypoxia induced by giving the ewes approximately 10% oxygen in
      nitrogen to breathe. As fetal arterial PO(2) decreased from 21.1 +/- 0.5 to 10.7
      +/- 0.4 Torr during a 30-min period, cerebral perfusion increased progressively
      to 56 +/- 8% above baseline. Perfusion then returned to baseline levels during a
      30-min recovery period. These responses are quantitatively similar to those spot
      observations that have been recorded earlier using labeled microspheres. We
      conclude that cerebral perfusion can be successfully measured by using laser
      Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an
      experimental model. With this method, relative changes of perfusion from a small
      volume of the ovine fetal brain can be measured on a continuous basis, and
      movement artifacts can be reduced to 5% of measured flow values.

PMID- 10956353
TI  - Skeletal muscle oxidative capacity in young and older women and men.
AB  - It has been suggested that a decline in skeletal muscle oxidative capacity is a
      general consequence of aging in humans. However, previous studies have not always
      controlled for the effects of varying levels of physical activity on muscle
      oxidative capacity. To test the hypothesis that, when matched for comparable
      habitual physical activity levels, there would be no age-related decline in the
      oxidative capacity of a locomotor muscle, the postexercise recovery time of
      phosphocreatine was compared in the tibialis anterior muscle of young [n = 19;
      33.8 +/- 4.8 (SD) yr] and older [n = 18; 75.5 +/- 4.5 yr] healthy women and men
      of similar, relatively low, activity levels. The intramuscular metabolic
      measurements were accomplished by using phosphorus magnetic resonance
      spectroscopy. The results indicate that there was no age effect on the
      postexercise recovery time of phosphocreatine recovery, thus supporting the
      stated hypothesis. These data suggest that there is no requisite decline in
      skeletal muscle oxidative capacity with aging in humans, at least through the
      seventh decade.

PMID- 10956354
TI  - Gastrointestinal function during exercise: comparison of water, sports drink, and
      sports drink with caffeine.
AB  - Caffeine is suspected to affect gastrointestinal function. We therefore
      investigated whether supplementation of a carbohydrate-electrolyte solution (CES)
      sports drink with 150 mg/l caffeine leads to alterations in gastrointestinal
      variables compared with a normal CES and water using a standardized rest-exercise
      rest protocol. Ten well-trained subjects underwent a rest-cycling-rest protocol
      three times. Esophageal motility, gastroesophageal reflux, and intragastric pH
      were measured by use of a transnasal catheter. Orocecal transit time was measured
      using breath-H(2) measurements. A sugar absorption test was applied to determine
      intestinal permeability and glucose absorption. Gastric emptying was measured via
      the (13)C-acetate breath test. In the postexercise episode, midesophageal
      pressure was significantly lower in the CES + caffeine trial compared with the
      water trial (P = 0.017). There were no significant differences between the three
      drinks for gastric pH and reflux during the preexercise, the cycling, and the
      postexercise episode, respectively. Gastric emptying, orocecal transit time, and
      intestinal permeability showed no significant differences between the three
      trials. However, glucose absorption was significantly increased in the CES +
      caffeine trial compared with the CES trial (P = 0.017). No significant
      differences in gastroesophageal reflux, gastric pH, or gastrointestinal transit
      could be observed between the CES, the CES + caffeine, and the water trials.
      However, intestinal glucose uptake was increased in the CES + caffeine trial.

PMID- 10956355
TI  - beta-adrenergic blockade augments glucose utilization in horses during graded
      exercise.
AB  - To examine the role of beta-adrenergic mechanisms in the regulation of endogenous
      glucose (Glu) production [rate of appearance (R(a))] and utilization [rate of
      disappearance (R(d))] and carbohydrate (CHO) metabolism, six horses completed
      consecutive 30-min bouts of exercise at approximately 30% (Lo) and approximately
      60% (Hi) of estimated maximum O(2) uptake with (P) and without (C) prior
      administration of the beta-blocker propranolol (0.22 mg/kg iv). All horses
      completed exercise in C; exercise duration in P was 49.9 +/- 1.2 (SE) min. Plasma
      Glu was unchanged in C during Lo but increased progressively in Hi. In P, plasma
      Glu rose steadily during Lo and Hi and was higher (P < 0.05) than in C throughout
      exercise. Plasma insulin declined during exercise in P but not in C; beta
      blockade attenuated (P < 0.05) the rise in plasma glucagon and free fatty acids
      and exaggerated the increases in epinephrine and norepinephrine. Glu R(a) was 8.1
      +/- 0.8 and 8.4 +/- 1.0 micromol. kg(-1). min(-1) at rest and 30.5 +/- 3.6 and
      42.8 +/- 4.1 micromol. kg(-1). min(-1) at the end of Lo in C and P, respectively.
      During Hi, Glu R(a) increased to 54.4 +/- 4.4 and 73.8 +/- 4.7 micromol. kg(-1).
      min(-1) in C and P, respectively. Similarly, Glu R(d) was approximately 40%
      higher in P than in C during Lo (27.3 +/- 2.0 and 39.5 +/- 3.3 micromol. kg(-1).
      min(-1) in C and P, respectively) and Hi (37.4 +/- 2.6 and 61.5 +/- 5.3 micromol.
      kg(-1). min(-1) in C and P, respectively). beta-Blockade augmented CHO oxidation
      (CHO(ox)) with a concomitant reduction in fat oxidation. Inasmuch as estimated
      muscle glycogen utilization was similar between trials, the increase in CHO(ox)
      in P was due to increased use of plasma Glu. We conclude that beta-blockade
      increases Glu R(a) and R(d) and CHO(ox) in horses during exercise. The increase
      in Glu R(d) under beta-blockade suggests that beta-adrenergic mechanisms restrain
      Glu R(d) during exercise.

PMID- 10956357
TI  - Denervation alters myosin heavy chain expression and contractility of developing
      rat diaphragm muscle.
AB  - We hypothesized that unilateral denervation (DNV) of the rat diaphragm muscle
      (Dia(m)) in neonates at postnatal day 7 (D-7) alters normal transitions of myosin
      heavy chain (MHC) isoform expression and thereby affects postnatal changes in
      maximum specific force (P(o)) and maximum unloaded shortening velocity (V(o)).
      The relative expression of different MHC isoforms was analyzed
      electrophoretically. With DNV at D-7, expression of MHC(neo) in the Dia(m)
      persisted, and emergence of MHC(2X) and MHC(2B) was delayed. By D-21 and D-28,
      relative expression of MHC(2A) and MHC(2B) was reduced in DNV compared with
      control (CTL) animals. Expression of MHC(neo) also reappeared in adult Dia(m) by
      2-3 wk after DNV, and relative expression of MHC(2B) was reduced. At each age,
      P(o) was reduced and V(o) was slowed by DNV, compared with CTL. In CTL Dia(m),
      postnatal changes in P(o) and V(o) were associated with an increase in fast MHC
      isoform expression. In DNV Dia(m), no such association existed. We conclude that,
      in the Dia(m), DNV induces alterations in both MHC isoform expression and
      contractile properties, which are not necessarily causally linked.

PMID- 10956356
TI  - Sprint training restores normal contractility in postinfarction rat myocytes.
AB  - The significance of 6-8 wk of high-intensity sprint training (HIST) on
      contractile abnormalities of myocytes isolated from rat hearts with prior
      myocardial infarction (MI) was investigated. Compared with the sedentary (Sed)
      condition, HIST attenuated myocyte hypertrophy observed post-MI primarily by
      reducing cell lengths but not cell widths. At high extracellular Ca(2+)
      concentration (5 mM) and low pacing frequency (0.1 Hz), conditions that
      preferentially favored Ca(2+) influx over efflux, MI-Sed myocytes shortened less
      than Sham-Sed myocytes did. HIST significantly improved contraction amplitudes in
      MI myocytes. Under conditions that favored Ca(2+) efflux, i.e., low extracellular
      Ca(2+) concentration (0.6 mM) and high pacing frequency (2 Hz), MI-Sed myocytes
      contracted more than Sham-Sed myocytes. HIST did not appreciably affect
      contraction amplitudes of MI myocytes under these conditions. Compared with MI
      Sed myocytes, HIST myocytes showed significant improvement in time required to
      reach one-half maximal contraction amplitude shortening, maximal myocyte
      shortening and relengthening velocities, and half time of relaxation. Our results
      indicate that HIST instituted shortly after MI improved cellular contraction in
      surviving myocytes. Because our previous studies demonstrated that, in post-MI
      myocytes, HIST improved intracellular Ca(2+) dynamics, enhanced sarcoplasmic
      reticulum Ca(2+) uptake and Ca(2+) content, and restored Na(+)/Ca(2+) exchange
      current toward normal, we hypothesized that improvement in MI myocyte contractile
      function by HIST was likely mediated by normalization of cellular Ca(2+)
      homeostatic mechanisms.

PMID- 10956358
TI  - Nasal resistance and flow resistive work of nasal breathing during exercise:
      effects of a nasal dilator strip.
AB  - Using posterior rhinomanometry, we measured nasal airflow resistance (Rn) and
      flow-resistive work of nasal breathing (WONB), with an external nasal dilator
      strip (ENDS) and without (control), in 15 healthy adults (6 men, 9 women) during
      exclusive nasal breathing and graded (50-230 W) exercise on a cycle ergometer.
      ENDS decreased resting inspiratory and/or expiratory Rn (at 0.4 l/s) by >0.5
      cmH(2)O. l(-1). s in 11 subjects ("responders"). Inspired ventilation (VI)
      increased with external work rate, but tended to be greater with ENDS.
      Inspiratory and expiratory Rn (at 0.4 l/s) decreased as VI increased but, in
      responders, tended to remain lower with ENDS. Inspiratory (but not expiratory) Rn
      at peak nasal airflow (Vn) increased as VI increased but, again, was lower with
      ENDS. At a VI of approximately 35 l/min, ENDS decreased flow limitation and
      hysteresis of the inspiratory transnasal pressure-flow curve. In responders, ENDS
      reduced inspiratory WONB per breath and inspiratory nasal power values during
      exercise. We conclude that ENDS stiffens the lateral nasal vestibule walls and,
      in responders, may reduce the energy required for nasal ventilation during
      exercise.

PMID- 10956359
TI  - Impact of muscle injury and accompanying inflammatory response on
      thermoregulation during exercise in the heat.
AB  - This study examined whether muscle injury and the accompanying inflammatory
      responses alter thermoregulation during subsequent exercise-heat stress. Sixteen
      subjects performed 50 min of treadmill exercise (45-50% maximal O(2) consumption)
      in a hot room (40 degrees C, 20% relative humidity) before and at select times
      after eccentric upper body (UBE) and/or eccentric lower body (LBE) exercise. In
      experiment 1, eight subjects performed treadmill exercise before and 6, 25, and
      30 h after UBE and then 6, 25, and 30 h after LBE. In experiment 2, eight
      subjects performed treadmill exercise before and 2, 7, and 26 h after LBE only.
      UBE and LBE produced marked soreness and significantly elevated creatine kinase
      levels (P < 0.05), but only LBE increased (P < 0.05) interleukin-6 levels. In
      experiment 1, core temperatures before and during exercise-heat stress were
      similar for control and after UBE, but some evidence for higher core temperatures
      was found after LBE. In experiment 2, core temperatures during exercise-heat
      stress were 0.2-0.3 degrees C (P < 0.05) above control values at 2 and 7 h after
      LBE. The added thermal strain after LBE (P < 0.05) was associated with higher
      metabolic rate (r = 0.70 and 0.68 at 2 and 6-7 h, respectively) but was not
      related (P > 0.05) to muscle soreness (r = 0.47 at 6-7 h), plasma interleukin-6
      (r = 0.35 at 6-7 h), or peak creatine kinase levels (r = 0.22). Local sweating
      responses (threshold core temperature and slope) were not altered by UBE or LBE.
      The results suggest that profuse muscle injury can increase body core temperature
      during exercise-heat stress and that the added heat storage cannot be attributed
      solely to increased heat production.

PMID- 10956360
TI  - Role of neuronal nitric oxide synthase in hypoxia-induced anapyrexia in rats.
AB  - Anapyrexia (a regulated decrease in body temperature) is a response to hypoxia
      that occurs in organisms ranging from protozoans to mammals, but very little is
      known about the mechanisms involved. Recently, it has been shown that the NO
      pathway plays a major role in hypoxia-induced anapyrexia. However, very little is
      known about which of the three different nitric oxide synthase isoforms
      (neuronal, endothelial, or inducible) is involved. The present study was designed
      to test the hypothesis that neuronal nitric oxide synthase (nNOS) plays a role in
      hypoxia-induced anapyrexia. Body core temperature (T(c)) of awake, unrestrained
      rats was measured continuously using biotelemetry. Rats were submitted to
      hypoxia, 7-nitroindazole (7-NI; a selective nNOS inhibitor) injection, or both
      treatments together. Control animals received vehicle injections of the same
      volume. We observed a significant (P < 0.05) reduction in T(c) of approximately
      2.8 degrees C after hypoxia (7% inspired O(2)), whereas intraperitoneal injection
      of 7-NI at 25 mg/kg caused no significant change in T(c). 7-NI at 30 mg/kg
      elicited a reduction in T(c) and was abandoned in further experiments. When the
      two treatments were combined (25 mg/kg of 7-NI and 7% inspired O(2)), we observed
      a significant attenuation of hypoxia-induced anapyrexia. The data indicate that
      nNOS plays a role in hypoxia-induced anapyrexia.

PMID- 10956361
TI  - Muscle afferent activity modulates bioassayable growth hormone in human plasma.
AB  - Immunoassayable and bioassayable growth hormone responses to vibration-induced
      activation of muscle spindle afferents of the soleus (Sol) or tibialis anterior
      (TA) muscles were studied in 10 men. Subjects were supine while a 10-min
      vibration stimulus (100 Hz; 1.5-mm amplitude) was applied to the muscle, with
      each of the muscles tested on separate days. Blood samples were collected before,
      during, immediately after, and after 5 and 10 min of vibration. Plasma growth
      hormone concentrations were determined by radioimmunoassay (IGH) for all sampling
      periods and by bioassay (BGH; measurement of tibial epiphysial cartilage growth
      in hypophysectomized rats) for samples obtained before and immediately after
      vibration. Plasma IGH concentrations were similar at all time points during the
      Sol or TA experiments. After 10 min of muscle vibration, mean plasma BGH was
      elevated 94% [1,216 +/- 148 (SD) to 2, 362 +/- 487 microg/l; P = 0.0001] for TA
      and decreased 22% (1,358 +/- 155 to 1,058 +/- 311 microg/l; P = 0.09) for Sol.
      These data demonstrate that activation of TA muscle spindle afferents increases
      circulating BGH but not IGH. The absence of a similar vibration-induced BGH
      response for the Sol indicates a differential regulation of BGH release by these
      two predominantly slow muscles, perhaps related to their respective flexor and
      extensor functions. These data indicate that a muscle afferent-pituitary axis
      modulates the release of BGH, but not IGH, from the pituitary in humans and that
      this axis is muscle specific, similar to that observed in rats.

PMID- 10956362
TI  - Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine
      D(2) receptors.
AB  - We used genetically engineered D(2) receptor-deficient [D(2)-(-/-)] and wild-type
      [D(2)-(+/+)] mice to test the hypothesis that dopamine D(2) receptors modulate
      the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)]
      and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent
      changes in ventilation during chronic hypoxia. HVR was independent of gender in
      D(2)-(+/+) mice and significantly greater in D(2)-(-/-) than in D(2)-(+/+) female
      mice. HCVR was significantly greater in female D(2)-(+/+) mice than in male D(2)
      (+/+) and was greater in D(2)-(-/-) male mice than in D(2)-(+/+) male mice.
      Exposure to hypoxia for 2-8 days was studied in male mice only. D(2)-(+/+) mice
      showed time-dependent increases in "baseline" ventilation (inspired PO(2) = 214
      Torr) and hypoxic stimulated ventilation (inspired PO(2) = 70 Torr) after 8 days
      of acclimatization to hypoxia, but D(2)-(-/-) mice did not. Hence, dopamine D(2)
      receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and
      contribute to time-dependent changes in ventilation and the acute HVR during
      acclimatization to hypoxia.

PMID- 10956363
TI  - Glucose uptake is increased in trained vs. untrained muscle during heavy
      exercise.
AB  - Endurance training increases muscle content of glucose transporter proteins (GLUT
      4) but decreases glucose utilization during exercise at a given absolute
      submaximal intensity. We hypothesized that glucose uptake might be higher in
      trained vs. untrained muscle during heavy exercise in the glycogen-depleted
      state. Eight untrained subjects endurance trained one thigh for 3 wk using a knee
      extensor ergometer. The subjects then performed two-legged glycogen-depleting
      exercise and consumed a carbohydrate-free meal thereafter to keep muscle glycogen
      concentration low. The next morning, subjects performed dynamic knee extensions
      with both thighs simultaneously at 60, 80, and until exhaustion at 100% of each
      thigh's peak workload. Glucose uptake was similar in both thighs during exercise
      at 60% of thigh peak workload. At the end of 80 and at 100% of peak workload,
      glucose uptake was on average 33 and 22% higher, respectively, in trained
      compared with untrained muscle (P < 0.05). Training increased the muscle content
      of GLUT-4 by 66% (P < 0. 05). At exhaustion, glucose extraction correlated
      significantly (r = 0.61) with total muscle GLUT-4 protein. Thus, when working at
      a high load with low glycogen concentrations, muscle glucose uptake is
      significantly higher in trained than in untrained muscle. This may be due to the
      higher GLUT-4 protein concentration in trained muscle.

PMID- 10956364
TI  - Effects of anodal vs. cathodal pacing on the mechanical performance of the
      isolated rabbit heart.
AB  - Previous studies have suggested that anodal pacing enhances electrical conduction
      in the heart near the pacing site. It was hypothesized that enhanced conduction
      by anodal pacing would also enhance ventricular pressure in the heart. Left
      ventricular pressure measurements were made in isolated, Langendorff-perfused
      rabbit hearts by means of a Millar pressure transducer with the use of a balloon
      catheter fixed in the left ventricle. The pressure wave was analyzed for maximum
      pressure (Pmax) generated in the left ventricle and the work done by the left
      ventricle (Parea). Eight hearts were paced with monophasic square-wave pulses of
      varying amplitudes (2, 4, 6, and 8 V) with 100 pulses of each waveform delivered
      to the epicardium. Anodal stimulation pulses showed statistically significant
      improvement in mechanical response at 2, 4, and 8 V. Relative to unipolar
      cathodal pacing, unipolar anodal pacing improved Pmax by 4.4 +/- 2.3 (SD), 5.3 +/
      3.1, 3.5 +/- 4.9, and 4.8 +/- 1.9% at 2, 4, 6, and 8 V, respectively. Unipolar
      anodal stimulation also improved Parea by 9.0 +/- 3.0, 12.0 +/- 6.0, 10.1 +/-
      7.7, and 11.9 +/- 6.0% at 2, 4, 6, and 8 V, respectively. Improvements in Pmax
      and Parea indicate that an anodally paced heart has a stronger mechanical
      response than does a cathodally paced heart. Anodal pacing might be useful as a
      novel therapeutic technology to treat mechanically impaired or failed hearts.

PMID- 10956365
TI  - Protein- and carbohydrate-induced augmentation of whole body creatine retention
      in humans.
AB  - This study investigated the effect of creatine supplementation in conjunction
      with protein and/or carbohydrate (CHO) ingestion on plasma creatine and serum
      insulin concentrations and whole body creatine retention. Twelve men consumed 4 x
      5 g of creatine on four occasions in combination with 1) 5 g of CHO, 2) 50 g of
      protein and 47 g of CHO, 3) 96 g of CHO, or 4) 50 g of CHO. The increase in serum
      insulin was no different when the protein-CHO and high-CHO treatments were
      compared, but both were greater than the response recorded for the low-CHO
      treatment (both P < 0.05). As a consequence, body creatine retention was
      augmented by approximately 25% for protein-CHO and high-CHO treatments compared
      with placebo treatment. The areas under creatine- and insulin-time curves were
      related during the first oral challenge (r = -0.920, P < 0.05) but not after the
      fourth (r = -0.342). It is concluded, first, that the ingestion of creatine in
      conjunction with approximately 50 g of protein and CHO is as effective at
      potentiating insulin release and creatine retention as ingesting creatine in
      combination with almost 100 g of CHO. Second, the stimulatory effect of insulin
      on creatine disposal was diminished within the initial 24 h of supplementation.

PMID- 10956366
TI  - Bronchial hyperreactivity is associated with enhanced grain dust-induced airflow
      obstruction.
AB  - Bronchial hyperreactivity (BHR) is associated with the presence of airway
      inflammation in asthma and is seen in individuals occupationally exposed to grain
      dust. To better understand the relationship between BHR and pulmonary
      inflammation after grain dust exposure, we carried out an inhalation challenge to
      corn dust extract (CDE) on seven subjects with BHR [a 20% or greater decrease in
      forced expiratory volume in 1 s (FEV(1)) compared with diluent FEV(1) with a
      cumulative dose of histamine </=47.3 breath units] and compared their
      physiological and inflammatory responses with those of seven matched control
      subjects. BHR subjects were exposed to nebulized CDE (target dose of 0.16
      microg/kg endotoxin) as tolerated; matched controls received equal amounts of
      CDE. Subjects with BHR complained of chest tightness and dyspnea within the 2 h
      after inhalation of CDE significantly more frequently than controls. Similarly,
      subjects with BHR developed significantly greater percent declines in FEV(1) at
      time points up to 4 h after exposure to CDE. Significant increases in total
      cells, neutrophils, tumor necrosis factor-alpha, interleukin-6, and interleukin-8
      were detected in bronchoalveolar lavage fluid 4 h after inhalation of CDE in all
      subjects, but no differences were detected between the control and BHR groups.
      These results suggest that, although subjects with BHR develop a more precipitous
      decline in FEV(1) after exposure to CDE, the inflammatory response to CDE is
      similar in subjects with and without BHR.

PMID- 10956367
TI  - Reduced strength after passive stretch of the human plantarflexors.
AB  - The purpose of this study was to assess strength performance after an acute bout
      of maximally tolerable passive stretch (PS(max)) in human subjects. Ten young
      adults (6 men and 4 women) underwent 30 min of cyclical PS(max) (13 stretches of
      135 s each over 33 min) and a similar control period (Con) of no stretch of the
      ankle plantarflexors. Measures of isometric strength (maximal voluntary
      contraction), with twitch interpolation and electromyography, and twitch
      characteristics were assessed before (Pre), immediately after (Post), and at 5,
      15, 30, 45, and 60 min after PS(max) or Con. Compared with Pre, maximal voluntary
      contraction was decreased at Post (28%) and at 5 (21%), 15 (13%), 30 (12%), 45
      (10%), and 60 (9%) min after PS(max) (P < 0.05). Motor unit activation and
      electromyogram were significantly depressed after PS(max) but had recovered by 15
      min. An additional testing trial confirmed that the torque-joint angle relation
      may have been temporarily altered, but at Post only. These data indicate that
      prolonged stretching of a single muscle decreases voluntary strength for up to 1
      h after the stretch as a result of impaired activation and contractile force in
      the early phase of deficit and by impaired contractile force throughout the
      entire period of deficit.

PMID- 10956368
TI  - Increases in submaximal cycling efficiency mediated by altitude acclimatization.
AB  - To investigate the hypothesis that respiratory gas exchange and, in particular,
      the O(2) consumption (VO(2)) response to exercise is altered after a 21-day
      expedition to 6,194 m, five male climbers (age 28.2 +/- 2 yr; weight 76.9 +/- 4.3
      kg; means +/- SE) performed a progressive and prolonged two-step cycle test both
      before and 3-4 days after return to sea level. During both exercise tests, a
      depression (P < 0.05) in VO(2) (l/min) and an increase (P < 0.05) in minute
      ventilation (VE BTPS; l/min) and respiratory exchange ratio were observed after
      the expedition. These changes occurred in the absence of changes in CO(2)
      production (l/min). During steady-state submaximal exercise, net efficiency,
      calculated from the rates of the mechanical power output to the energy expended
      (VO(2)) above that measured at rest, increased (P < 0.05) from 25.9 +/- 1.6 to
      31. 3 +/- 1.3% at the lighter power output and from 24.4 +/- 1.3 to 29.5 +/- 1.5%
      at the heavy power output. These changes were accompanied by a 4.5% reduction (P
      < 0.05) in peak VO(2) (3.99 +/- 0.17 vs. 3.81 +/- 0.18 l/min). After the
      expedition, an increase (P < 0.05) in hemoglobin concentration (15.0 +/- 0.49 vs.
      15.8 +/- 0.41 g/100 ml) was found. It is concluded that, because resting VO(2)
      was unchanged, net efficiency is enhanced during submaximal exercise after a
      mountaineering expedition when the exercise is performed soon after return to sea
      level conditions.

PMID- 10956369
TI  - Acellular hemoglobin solution enters compressed lung capillaries more readily
      than red blood cells.
AB  - High lung inflation pressures compress alveolar septal capillaries, impede red
      cell transit, and interfere with oxygenation. However, recently introduced
      acellular hemoglobin solutions may enter compressed lung capillaries more easily
      than red blood cells. To test this hypothesis, we perfused isolated rat lungs
      with fluorescently labeled diaspirin cross-linked hemoglobin (DCLHb; 10%) and/ or
      autologous red cells (hematocrit, 20). Septal capillaries were compressed by
      setting lung inflation pressure above vascular pressures (zone 1). Examination by
      confocal microscopy showed that DCLHb was distributed throughout alveolar septa.
      Furthermore, this distribution was not affected by adding red blood cells to the
      perfusate. We estimated the maximum acellular hemoglobin mass within septa to be
      equivalent to that of 15 red blood cells. By comparison, we found an average of
      2.7 +/- 4.6 red cells per septum in zone 1. These values increased to 30.4 +/-
      25.8 and 50.4 +/- 22.1 cells per septum in zones 2 and 3, respectively. We
      conclude that perfusion in zone 1 with a 10% acellular hemoglobin solution may
      increase the hemoglobin concentration per septum up to fivefold compared with red
      cell perfusion.

PMID- 10956370
TI  - Role of endogenous nitric oxide in hyperoxia-induced airway hyperreactivity in
      maturing rats.
AB  - We sought to define the effects of maturation and hyperoxic stress on nitric
      oxide (NO)-induced modulation of bronchopulmonary responses to stimulation of
      vagal preganglionic nerve fibers. Experiments were performed on decerebrate,
      paralyzed, and ventilated rat pups at 6-7 days (n = 21) and 13-15 days of age (n
      = 23) breathing room air and on rat pups 13-15 days of age (n = 19) after
      exposure to hyperoxia (>/=95% inspired O(2) fraction for 4-6 days). Total lung
      resistance (RL) and lung elastance (EL) were measured by body plethysmograph.
      Vagal stimulation and release of acetylcholine caused a frequency-dependent
      increase in RL and EL in all animals. The RL response was significantly
      potentiated in normoxic animals by prior blockade of nitric oxide synthase (NOS)
      (P < 0.05). Hyperoxic exposure increased responses of RL to vagal stimulation (P
      < 0.05); however, after hyperoxic exposure, the potentiation of contractile
      responses by NOS blockade was abolished. The response of EL was potentiated by
      NOS blockade in the 13- to 15-day-old animals after both normoxic and hyperoxic
      exposure (P < 0.01). Morphometry revealed no effect of hyperoxic exposure on
      airway smooth muscle thickness. We conclude that NO released by stimulation of
      vagal preganglionic fibers modulates bronchopulmonary contractile responses to
      endogenously released acetylcholine in rat pups. Loss of this modulatory effect
      of NO could contribute to airway hyperreactivity after prolonged hyperoxic
      exposure, as may occur in bronchopulmonary dysplasia.

PMID- 10956371
TI  - Effects of transdermal nicotine treatment on structure and function of coronary
      artery bypass grafts.
AB  - Smoking is a major risk factor for failure of coronary artery bypass grafts
      (CABG). Experiments were designed to determine effects of transdermal nicotine,
      independent of smoking, on structure and function of CABG. Saphenous veins were
      placed as CABG in untreated dogs (control) or in dogs treated with transdermal
      nicotine (one 11-mg or two 22-mg patches/day) for 5 wk. Serum nicotine and plasma
      nitric oxide were measured. Grafts were removed and prepared for organ chamber
      studies and histology. Serum nicotine averaged 12.1 and 118.7 ng/ml in the 11
      mg/day and 44 mg/day groups, respectively. Plasma nitric oxide was higher in dogs
      treated with 11 mg/day doses compared with controls. In organ chamber studies,
      endothelium-dependent relaxations to thrombin and A-23187 and endothelium
      independent relaxations to nitric oxide were greatest in grafts from dogs treated
      with 11 mg/day doses. Intimal thickness of the grafts were similar among groups.
      However, staining for bone sialoprotein was increased in the media of grafts from
      the 11 mg/day treatment group. These data suggest that transdermal nicotine in
      doses comparable and double to those used for conventional smoking cessation
      treatment in humans does not adversely affect early patency of canine CABG up to
      4 wk postoperatively. Transdermal nicotine, however, may increase production of
      and response to nitric oxide in bypass grafts.

PMID- 10956372
TI  - Invited review: gravitational biology of the neuromotor systems: a perspective to
      the next era.
AB  - Earth's gravity has had a significant impact on the designs of the neuromotor
      systems that have evolved. Early indications are that gravity also plays a key
      role in the ontogenesis of some of these design features. The purpose of the
      present review is not to assess and interpret a body of knowledge in the usual
      sense of a review but to look ahead, given some of the general concepts that have
      evolved and observations made to date, which can guide our future approach to
      gravitational biology. We are now approaching an era in gravitational biology
      during which well-controlled experiments can be conducted for sustained periods
      in a microgravity environment. Thus it is now possible to study in greater detail
      the role of gravity in phylogenesis and ontogenesis. Experiments can range from
      those conducted on the simplest levels of organization of the components that
      comprise the neuromotor system to those conducted on the whole organism.
      Generally, the impact of Earth's gravitational environment on living systems
      becomes more complex as the level of integration of the biological phenomenon of
      interest increases. Studies of the effects of gravitational vectors on neuromotor
      systems have and should continue to provide unique insight into these mechanisms
      that control and maintain neural control systems designed to function in Earth's
      gravitational environment. A number of examples are given of how a gravitational
      biology perspective can lead to a clearer understanding of neuromotor disorders.
      Furthermore, the technologies developed for spaceflight studies have contributed
      and should continue to contribute to studies of motor dysfunctions, such as
      spinal cord injury and stroke. Disorders associated with energy support and
      delivery systems and how these functions are altered by sedentary life styles at
      1 G and by space travel in a microgravity environment are also discussed.

PMID- 10956373
TI  - Commentary

PMID- 10956374
TI  - Selected contribution: measuring the response time of pulmonary capillary
      recruitment to sudden flow changes.
AB  - To determine how rapidly pulmonary capillaries recruit after sudden changes in
      blood flow, we used an isolated canine lung lobe perfused by two pumps running in
      parallel. When one pump was turned off, flow was rapidly halved; when it was
      turned on again, flow immediately doubled. We recorded pulmonary capillary
      recruitment in subpleural alveoli using videomicroscopy to measure how rapidly
      the capillaries reached a new steady state after these step changes in blood
      flow. When flow was doubled, capillary recruitment reached steady state in <4 s.
      When flow was halved, steady state was reached in approximately 8 s. We conclude
      that the pulmonary microcirculation responds rapidly to step changes in flow,
      even in the capillaries that are most distant from the hilum.

PMID- 10956375
TI  - Selected contribution: redistribution of pulmonary perfusion during
      weightlessness and increased gravity.
AB  - To compare the relative contributions of gravity and vascular structure to the
      distribution of pulmonary blood flow, we flew with pigs on the National
      Aeronautics and Space Administration KC-135 aircraft. A series of parabolas
      created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres
      of varying colors were injected into the pulmonary circulation to mark regional
      blood flow during different postural and gravitational conditions. The lungs were
      subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces.
      Flow to each piece was determined for the different conditions. Perfusion
      heterogeneity did not change significantly during weightlessness compared with
      normal and increased gravitational forces. Regional blood flow to each lung piece
      changed little despite alterations in posture and gravitational forces. With the
      use of multiple stepwise linear regression, the contributions of gravity and
      vascular structure to regional perfusion were separated. We conclude that both
      gravity and the geometry of the pulmonary vascular tree influence regional
      pulmonary blood flow. However, the structure of the vascular tree is the primary
      determinant of regional perfusion in these animals.

PMID- 10956376
TI  - "You can't get there from here," Zeno says.

PMID- 10956377
TI  - Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine,
      and L-carnitine.
AB  - The role of antioxidants in preventing apoptosis and viral activation in HIV is
      well documented. N-acetylcysteine, glutathione, and alpha-lipoic acid have been
      shown to interrupt the process of viral activation and CD4 cell death. L
      glutamine has been shown to improve glutathione levels and significantly increase
      lean body mass in HIV infection. The literature on the use of L-carnitine and
      acetyl-L-carnitine in treating mitochondrial toxicity, both in muscle and nerve
      pathologies is relevant in nutritional treatment of HIV, given the mitochondrial
      toxicity of nucleoside analog reverse transcriptase inhibitor therapy. The
      current use of highly active antiviral therapies, their toxicity, and significant
      failure rates have created the need for a more conservative reassessment of HIV
      treatment. The adjunctive use of nutrient therapy in the treatment of HIV is
      reviewed here.

PMID- 10956378
TI  - Peripheral metabolism of thyroid hormones: a review.
AB  - Peripheral metabolism of thyroid hormones is a critical component of the impact
      these hormones have on intracellular function. Thyroid hormones can be
      metabolized in peripheral tissue by deiodination, conjugation, deamination, and
      decarboxylation enzyme reactions. Therefore, alterations in these metabolic
      pathways might significantly impact the quantity of specific thyroid hormone
      metabolites influencing function at the cellular level. Available evidence also
      suggests that, under some circumstances, the activity of hepatic antioxidant
      enzyme systems and lipid peroxidation might influence the peripheral metabolism
      of thyroid hormones. Several syndromes, such as "euthyroid sick syndrome" and
      "low T3 syndrome," have been classified within the medical literature. The common
      feature of these disorders is a low level of circulating T3, with generally
      normal to slightly elevated blood T4 levels and either normal or slightly
      suppressed TSH levels. This pattern of altered thyroid hormone levels is
      generally agreed to be a result of impairment in extra-thyroidal peripheral
      metabolism. Hepatic and renal pathology, as well as catabolic states such as
      those induced subsequent to severe injury, illness, or trauma result in
      consistent shifts in the thyroid hormone profile, secondary to their impact on
      peripheral enzyme pathways. Lifestyle factors, such as stress, caloric
      restriction, and exercise, influence peripheral metabolism of thyroid hormones.
      Exposure to toxic metals, chemical poisons, and several drugs can also influence
      the peripheral fate of thyroid hormones. While the role of vitamins, minerals,
      and botanical extracts in thyroid hormone metabolism requires further
      elucidation, current evidence supports a role for selenium in the hepatic 5'
      deiodination enzyme.

PMID- 10956379
TI  - Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a
      review.
AB  - OBJECTIVE: The objective of this paper is to review the literature regarding
      Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine.
      Specifically, the literature was reviewed for articles pertaining to chemical
      properties, therapeutic benefits, and toxicity. DESIGN: This review is in a
      narrative format and consists of all publications relevant to ashwagandha that
      were identified by the authors through a systematic search of major computerized
      medical databases; no statistical pooling of results or evaluation of the quality
      of the studies was performed due to the widely different methods employed by each
      study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory,
      antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and
      rejuvenating properties. It also appears to exert a positive influence on the
      endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action
      for these properties are not fully understood. Toxicity studies reveal that
      ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have
      found various constituents of ashwagandha exhibit a variety of therapeutic
      effects with little or no associated toxicity. These results are very encouraging
      and indicate this herb should be studied more extensively to confirm these
      results and reveal other potential therapeutic effects. Clinical trials using
      ashwagandha for a variety of conditions should also be conducted.

PMID- 10956380
TI  - Peripheral intravenous nutrition therapy: outpatient, office-based
      administration.
AB  - BACKGROUND: The use of peripheral intravenous nutrition (PIN) has been growing in
      recent years due to the increase in awareness of the pathophysiological
      mechanisms of peripheral vein thrombophlebitis, as well as the availability of
      techniques to prevent or retard its onset. With the increase in public and
      medical practitioner awareness of the importance of nutritional interventions in
      health and disease, more outpatient-based PIN therapy is being performed.
      Outpatient, office-based PIN has unique features including high osmolality, high
      infusion rates, and short infusion duration. METHODS: Previous intravenous
      nutrition studies were used to estimate safety parameters for outpatient, office
      based PIN. CONCLUSIONS: Osmolalities of the infusion can approach 1000 mOsm/L if
      the duration of the infusion is only several hours. The infusion should be
      diluted to reduce the osmolality, even if an increase in infusion rate is
      necessary. Duration of infusion should be less than three hours to reduce the
      time the irritating mixture contacts the vein wall. This requires high (150 - 330
      mL/hour) infusion rates. The largest vein, and smallest and shortest catheter
      possible to achieve the infusion rate desired should be used, with in-line
      filtration of at least 0.45mm. The cannula should be removed at the first sign of
      pain or redness. Standard procedures to reduce infection risks should be
      followed.

PMID- 10956381
TI  - Hepatitis C; a retrospective study, literature review, and naturopathic protocol.
AB  - The standard medical treatment of hepatitis C infection is only associated with
      sustained efficacy in a minority of patients. Therefore, the search for other
      treatments is of utmost importance. Several natural products and their
      derivatives have demonstrated benefit in the treatment of hepatitis C and other
      chronic liver conditions. Other herbal and nutritional supplements have
      mechanisms of action that make them likely to be of benefit. This article
      presents comprehensive protocol, including diet, lifestyle, and therapeutic
      interventions. The authors performed a retrospective review of 41 consecutive
      hepatitis C patients. Of the 14 patients with baseline and follow-up data who had
      not undergone interferon therapy, seven had a greater than 25-percent reduction
      in serum alanine aminotransferase (ALT) levels after at least one month on the
      protocol. For all patients reviewed, the average reduction in ALT was 35 U/L
      (p=0.026). These data appear to suggest that a conservative approach using diet
      and lifestyle modification, along with safe and indicated interventions, can be
      effective in the treatment of hepatitis C. Controlled trials with serial liver
      biopsy and viral load data are necessary to confirm these preliminary findings.

PMID- 10956382
TI  - Green tea.
AB  - Tea is one of the most widely consumed beverages in the world today, second only
      to water, and its medicinal properties have been widely explored. The tea plant,
      Camellia sinensis, is a member of the Theaceae family, and black, oolong, and
      green tea are produced from its leaves. It is an evergreen shrub or tree and can
      grow to heights of 30 feet, but is usually pruned to 2-5 feet for cultivation.
      The leaves are dark green, alternate and oval, with serrated edges, and the
      blossoms are white, fragrant, and appear in clusters or singly. Unlike black and
      oolong tea, green tea production does not involve oxidation of young tea leaves.
      Green tea is produced from steaming fresh leaves at high temperatures, thereby
      inactivating the oxidizing enzymes and leaving the polyphenol content intact. The
      polyphenols found in tea are more commonly known as flavonols or catechins and
      comprise 30-40 percent of the extractable solids of dried green tea leaves. The
      main catechins in green tea are epicatechin, epicatechin-3-gallate,
      epigallocatechin, and epigallocatechin-3-gallate (EGCG), with the latter being
      the highest in concentration. Green tea polyphenols have demonstrated significant
      antioxidant, anticarcinogenic, anti-inflammatory, thermogenic, probiotic, and
      antimicrobial properties in numerous human, animal, and in vitro studies.

PMID- 10956383
TI  - Expression of heregulins and associations with the ErbB family of tyrosine kinase
      receptors in papillary thyroid carcinomas.
AB  - Heregulin (Hrg) growth factors are natural ligands for ErbB3 and ErbB4. Because
      these receptors are involved in papillary thyroid carcinomas, we studied
      expression of Hrgs in fresh-frozen thyroid tissue and analyzed for possible
      coexpressions among the 4 members of the ErbB family of growth factor receptors
      and Hrgs in papillary carcinomas. Immunohistochemistry for the Hrg precursor
      isoform (134 biopsies from 101 patients) showed nuclear immunostaining in 83% of
      papillary carcinomas but not in normal thyroid tissue. Cytoplasmic
      immunopositivity for the Hrg precursor isoform was moderate or strong in 78% of
      papillary carcinoma specimens and weak in 13% of normal thyroid tissue samples.
      Western blot for the Hrg precursor isoform showed the expected protein band of
      approximately 70 kDa in papillary carcinomas, but not in non-neoplastic thyroid
      biopsies. Whereas weak cytoplasmic immunostaining for the mature Hrg alpha,
      beta1, and beta3, was present in 48, 38, and 51% of papillary carcinomas,
      respectively, normal thyroid tissue samples were negative. Hrg mRNA was present
      in both tumor and nontumor tissue, with evidence of increased mRNA expression in
      5 of 12 papillary carcinomas. RT-PCR of hrg mRNA, with subsequent DNA sequencing,
      confirmed the presence of hrg alpha, beta1, beta2, and beta3 mRNA in papillary
      carcinomas. In 55 papillary carcinomas, increased cytoplasmic immunostaining of
      the ErbB2 and ErbB3 receptors was significantly associated with each other and
      with cytoplasmic epidermal growth factor receptor (EGFR) immunoreactivity,
      indicating a common regulatory mechanism. Cytoplasmic staining for Hrg beta3 was
      significantly associated with ErbB3 immunostaining, indicating this receptor as
      the cognate one. The overexpression and nuclear localization of the Hrg precursor
      isoform were not associated with the expression of ErbB-receptors. This may
      reflect an unknown mechanism of action, possibly independent of the ErbB receptor
      system.

PMID- 10956384
TI  - Folate depletion increases sensitivity of solid tumor cell lines to 5
      fluorouracil and antifolates.
AB  - Cancer cell lines in standard cell culture medium or in animal models are
      surrounded by an environment with relatively high folate (HF) levels, compared
      with folate levels in human plasma. In the present study we adapted 4 colon
      cancer (C26-A, C26-10, C26-G and WiDr) and 3 squamous cell carcinoma of the head
      and neck (HNSCC) cell lines (11B, 14C and 22B) to culture medium with low folate
      (LF) levels (2.5, 1.0 and 0.5 nM, respectively) and investigated whether folate
      depletion had an effect on sensitivity to antifolates and which mechanisms were
      involved. All LF cell lines showed a higher sensitivity to 5-fluorouracil (5-FU)
      alone or in combination with leucovorin (LV) (2-5-fold), to the thymidylate
      synthase (TS) inhibitors, AG337 (2-7-fold), ZD1694 (3-49-fold), ZD9331 (3-40
      fold), LY231514 (2-21-fold) or GW1843U89 (4-29-fold) or to the dihydrofolate
      reductase (DHFR) inhibitor PT523 (2-50-fold) compared with their HF variants
      cultured in standard medium containing up to 8 microM folic acid. LV could only
      increase sensitivity to 5-FU in HNSCC cell lines 14C and 14C/F. The differences
      in sensitivity could partially be explained by a 2-7-fold increased transport
      activity of the reduced folate carrier (RFC) in LF cell lines, whereas no
      significant change in folylpolyglutamate synthetase (FPGS) activity was observed.
      Furthermore, the protein expression and catalytic activity of the target enzyme
      TS were up to 7-fold higher in HF colon cancer cells compared with the LF
      variants (p < 0.05). Although the TS protein expression in LF HNSCC cells was
      also lower than in HF variants, the TS catalytic activity and FdUMP binding sites
      were up to 3-fold higher (p < 0.05). Thus, changes in TS levels were associated
      with differences in sensitivity. These results indicate that folate depletion was
      associated with changes in TS and RFC levels which resulted in an increase in
      sensitivity to 5-FU and antifolates. The folate levels in LF medium used in this
      study are more representative for folate levels in human plasma and therefore
      these data could be more predictive for the activity of 5-FU and antifolates in a
      clinical setting than results obtained from cell lines cultured in HF medium or
      in animal models.

PMID- 10956385
TI  - Up-regulation of cdc2 protein during paclitaxel-induced apoptosis.
AB  - Microtubule damages induced by paclitaxel inhibit proteasome-dependent
      degradation of cyclin B, resulting in a sustained activation of cyclin B/cdc2
      kinase and a cell cycle arrest in mitosis. It has been previously shown that this
      kinase activity is also required for paclitaxel-induced apoptosis. We found here
      that paclitaxel increased cdc2 mRNA and protein levels and led to an accumulation
      of cdc2 in the active dephosphorylated form in NIH-OVCAR-3 cells. The addition of
      cycloheximide inhibited the paclitaxel-induced increase in cdc2 protein level,
      further indicating that paclitaxel stimulates cdc2 synthesis. This increase in
      cdc2 synthesis is a consequence of paclitaxel-induced arrest in mitosis. Indeed,
      dual analysis of DNA and cdc2 protein contents indicated that cdc2 up-regulation
      occurred in cells arrested with a G2/M DNA content. Furthermore, no up-regulation
      of cdc2 protein was observed when paclitaxel-treated cells were prevented from
      entering mitosis by treatment with purvalanol A, a cyclin-dependent kinase (CDK)
      inhibitor, or stimulated to exit mitosis with 2-AP, a non-specific kinase
      inhibitor. In addition, when paclitaxel-induced apoptosis was inhibited by Bcl-2
      over-expression, cdc2 up-regulation did not occur, leading to a lower level of
      activation of the cyclin B/cdc2 complex. Taken together, these results indicated
      that paclitaxel-induced cdc2 protein synthesis participates in a positive
      feedback loop designed to increase the activity of cyclin B/cdc2 kinase and thus
      may play a role in paclitaxel-induced apoptosis.

PMID- 10956386
TI  - Cell cycle activation by c-myc in a burkitt lymphoma model cell line.
AB  - The product of the proto-oncogene c-myc (myc) is a potent activator of cell
      proliferation. In Burkitt lymphoma (BL), a human B-cell tumor, myc is
      consistently found to be transcriptionally activated by chromosomal
      translocation. The mechanisms by which myc promotes cell cycle progression in B
      cells is not known. As a model for myc activation in BL cells, we have
      established a human EBV-EBNA1 positive B-cell line, P493-6, in which myc is
      expressed under the control of a tetracycline regulated promoter. If the
      expression of myc is switched off, P493-6 cells arrest in G0/G1 in the presence
      of serum. Re-expression of myc activates the cell cycle without inducing
      apoptosis. myc triggers the expression of cyclin D2, cyclin E and Cdk4, followed
      by the activation of cyclin E-associated kinase and hyper-phosphorylation of Rb.
      The transcription factor E2F-1 is expressed in proliferating and arrested cells
      at constant levels. The Cdk inhibitors p16, p21, p27 and p57 are expressed at low
      or not detectable levels in proliferating cells and are not induced after
      repression of myc. Ectopic expression of p16 inhibits cell cycle progression.
      These data suggest that myc triggers proliferation of P493-6 cells by promoting
      the expression of a set of cell cycle activators but not by inactivating cell
      cycle inhibitors.

PMID- 10956387
TI  - Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for
      this candidate tumor suppressor gene.
AB  - The human homolog of the Drosophila seven in absentia gene (SIAH1) may play an
      important role in apoptosis and tumor suppression. Transcription of SIAH1 is up
      regulated in non-tumorigenic clonal populations of cells derived from 2 different
      tumorigenic parental cell lines. Intracellular SIAH1 mRNA concentration increases
      in intestinal cells as they migrate from the bottom of the crypt to the lumen,
      where they undergo apoptosis. Finally, SIAH1 is located on chromosome 16q12-q13,
      a region that is frequently deleted in a large variety of human tumors. These
      observations suggest SIAH1 as a candidate tumor suppressor gene that may be
      inactivated during tumorigenesis. To test this hypothesis, a search for mutation
      in the coding sequence of this gene was initiated in tumors exhibiting loss of
      heterozygosity (LOH) at 16q12-q13. No difference was found in 12 hepatocellular
      carcinomas, 19 breast carcinomas, 9 prostate carcinomas, 7 colon carcinomas and 5
      human cell lines derived from colon cancer. One silent sequence variant (C to T
      transition at amino acid 270) was observed in the FET colon carcinoma cell line.
      It was subsequently found once in a group of 100 unrelated individuals from the
      CEPH families. A rapid real-time quantitative RT-PCR fluorescent method shows
      that SIAH1 remained transcriptionally active in the 6 colon cancer-derived cell
      lines, and the expression is comparable to the normal colon tissue. Taken
      together, these observations suggest that although many tumors may have lost one
      SIAH1 allele, the second allele would not be the site of frequent somatic
      mutations and may even remain functional.

PMID- 10956388
TI  - Refinement of an ovarian cancer tumour suppressor gene locus on chromosome arm
      22q and mutation analysis of CYP2D6, SREBP2 and NAGA.
AB  - Loss of heterozygosity on chromosome 22q was detected in 53% of 123 ovarian
      carcinomas, suggesting the presence of at least one tumour suppressor gene. We
      have refined the location of one possible tumour suppressor gene to the region
      between the microsatellite markers D22S299 and CYP2D. Located within this region
      are the genes SREBP2 (sterol regulatory element binding protein 2) and NAGA (N
      acetyl-alpha-D-galactosaminidase). Investigation of the coding exons of these
      genes by single stranded conformational polymorphism/heteroduplex analysis failed
      to identify any somatic genetic alterations in 57 ovarian tumours which exhibited
      LOH on 22q13. The CYP2D gene locus straddles the distal boundary of the candidate
      region. Germline variants of the active CYP2D6 gene with differing abilities to
      metabolise specific substrates have been implicated in the development of various
      cancers. Comparison of the frequency of the two common germline mutations among
      258 ovarian tumours and 231 non-cancer controls did not reveal any significant
      differences between the two groups. This suggests that the known polymorphic
      variants of CYP2D6 are not involved in ovarian cancer predisposition. We also
      conclude that neither NAGA nor SREBP2 are likely to be mutated in ovarian
      carcinomas.

PMID- 10956389
TI  - Interferon regulatory factor-2 point mutations in human pancreatic tumors.
AB  - Interferon regulatory factor (IRF)-2, a member of the IRF family, is a
      transcription factor involved in the regulation of various interferon and virus
      stimulated genes and other genes. For example, IRF-2 is an activator of the
      interferon (IFN)-gamma-inducible MHC class II transactivator (CIITA) type IV
      promoter. It cooperates with IRF-1 in the activation of the CIITA type IV
      promoter and can co-occupy the IRF-E of the promoter with IRF-1. In a previous
      study, we identified an inactivating point mutation in the DNA binding domain of
      IRF-2 expressed in a human pancreatic tumor cell line that does not express CIITA
      or MHC class II in response to IFN-gamma. To further assess the potential impact
      of IRF-2 mutations in tumorigenesis, we screened fresh pancreatic tumor explants
      and identified 2 IRF-2 point mutations in the 2 alleles of IRF-2 from a single
      tumor specimen. Both mutations occurred in the DNA binding domain of IRF-2. DNA
      binding assays demonstrated that the IRF-2 point mutations impaired IRF-2 DNA
      binding. The transactivation function of the mutant IRF-2s was similarly
      impaired. This is the first report of IRF-2 mutations in human tumor explants.

PMID- 10956390
TI  - Risk of developing pancreatic cancer in families with familial atypical multiple
      mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden).
AB  - Familial atypical multiple mole melanoma (FAMMM) is an autosomal dominant disease
      characterized by the familial occurrence of malignant melanoma of the skin and
      multiple atypical precursor lesions. Germline mutations in the p16 (CDKN2A) gene
      have been reported in at least a quarter of such families. An association has
      been reported between p16 mutations and pancreatic cancer. The aim of this study
      was to assess the risk of developing pancreatic and other cancers in Dutch FAMMM
      families with a 19 bp deletion in exon 2 of the p16 gene (p16-Leiden). Mutation
      analysis was performed in 27 families suspected of FAMMM. Clinical and
      pathological data were collected from all relatives affected with cancer. A p16
      Leiden mutation was identified in 19 families. These families included 86
      patients with melanoma. The second most frequent cancer was pancreatic cancer,
      which was observed in 15 patients from 7 families. The mean age at diagnosis of
      pancreatic cancer was 58 years (range 38-77 years). The estimated cumulative risk
      of developing pancreatic cancer in putative mutation carriers by age 75 years was
      17%. In 8 p16-Leiden-negative families, no cases of pancreatic cancer occurred.
      p16 mutation carriers have a considerable risk of developing pancreatic cancer.
      Further studies should evaluate the value of surveillance of the pancreas in
      these high-risk families.

PMID- 10956392
TI  - Human papillomavirus type 16-immortalized endocervical cells selected for
      resistance to cisplatin are malignantly transformed and have a multidrug
      resistance phenotype.
AB  - Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is a highly effective
      chemotherapeutic agent against cervical cancer, but drug resistance is a major
      obstacle in its clinical application. The mechanism of drug resistance in human
      cervical cancer is not well understood. Here, we established an in vitro
      endocervical, cisplatin-resistant cell system that mimics the development of
      cisplatin resistance in the human cervix. Human papillomavirus (HPV) type 16
      immortalized human endocervical cells (HEN-16-2) were treated with cisplatin, and
      the cisplatin-selected cells (HEN-16-2/CDDP) were resistant to cisplatin,
      paclitaxel, actinomycin D, doxorubicin, etoposide, and 5-fluorouracil, thus
      demonstrating a multidrug resistance (MDR) phenotype. Furthermore, compared with
      a similar passage of drug-sensitive HEN-16-2 cells, HEN-16-2/CDDP cells exhibited
      the general growth characteristics of cancer cell lines: faster growth in medium
      containing serum and high calcium levels, higher saturation density, anchorage
      independent growth, and formation of tumors in nude mice. These results provided
      the first in vitro evidence that cisplatin selection can transform HPV
      immortalized endocervical cells and cause a phenotype of MDR.

PMID- 10956391
TI  - Germline alterations in the cyclooxygenase-2 gene are not associated with the
      development of extracolonic manifestations in a large swiss familial adenomatous
      polyposis kindred.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant condition leading
      to the development of multiple colorectal polyps and other features.
      Intrafamilial variation in phenotype is known to occur in FAP; despite carrying
      the same causing mutation in the APC gene, disease expression may considerably
      differ in affected individuals, likely due to the existence of modifier genes.
      Several lines of evidence suggest the cyclooxygenase-2 (COX-2) gene to be a
      candidate modifier in FAP. Since COX-2 appears to be expressed in tissues prone
      to be affected in FAP, it might influence the occurrence of extracolonic
      manifestations in this disorder. Herein, we investigated whether alterations in
      the COX-2 gene are involved in the development of extracolonic polyps and
      extragastrointestinal features. Mutational analysis using single-strand
      conformation polymorphism (SSCP) in 130 members of a FAP family displaying strong
      phenotype variation revealed 3 polymorphic sites within the coding region of the
      COX-2 gene. None of these allelic variants, however, segregated with a particular
      disease phenotype. In addition, expression analysis was performed in 31 family
      members with representative phenotypes. Neither of the two polymorphisms detected
      within the COX-2 promoter was associated with a given phenotype nor was there a
      significant difference in quality or quantity of COX-2 mRNA in lymphocytes as
      measured by reverse transcription- and real time quantitative reverse
      transcription PCR (RT-PCR and TaqMan). In conclusion, germline alterations in the
      COX-2 gene are unlikely to account for the development of extracolonic disease in
      FAP patients.

PMID- 10956393
TI  - IgA antibodies to the 27-kDa heat-shock protein in the genital tracts of women
      with gynecologic cancers.
AB  - Heat-shock proteins promote cell survival under adverse environmental conditions.
      Synthesis of the 27-kDa (HSP27), 70-kDa (HSP70), and 90-kDa (HSP90) heat-shock
      proteins is increased in malignantly transformed cells and has been associated
      with tumor proliferation, metastasis, and resistance to chemotherapeutic agents.
      The increased expression of heat-shock proteins and their association with tumor
      specific antigens may result in local immunity to the heat-shock proteins. We
      examined the occurrence of IgA antibodies to HSP27, HSP70, and HSP90 in the lower
      genital tracts of women with possible gynecologic cancers. Cervical samples were
      obtained from 119 consecutive women being evaluated for a gynecologic malignancy
      or returning for a follow-up examination following cancer treatment. Aliquots
      were tested for IgA anti-heat-shock protein antibodies by ELISA. Aliquots were
      also tested for IgG antibodies to HSP27 as well as for human papillomavirus. Anti
      HSP27 IgA was detected in 85.7% of 21 women with endometrial cancer tested prior
      to diagnosis and in 41.1% of 17 women tested after treatment. In women with
      ovarian cancer, 77.8% of 9 women tested prior to diagnosis and 75.0% of 24 women
      evaluated after treatment were anti-HSP27 IgA-positive. Of 6 women with cervical
      cancer tested prior to diagnosis, 5 were positive for this antibody. None of 25
      women with benign diagnoses or 46 healthy women were cervical IgA anti-HSP27
      positive (P < 0.0001). In contrast, anti-HSP27 IgG was not associated with a
      gynecologic malignancy. HSP27 cervical antibodies were not associated with the
      presence of human papillomavirus. Cervical IgA antibodies to HSP90 were
      associated with ovarian cancer; antibodies to HSP70 were not cancer-associated.
      We conclude that cervical IgA antibodies to HSP27 may be indicators of a
      gynecologic malignancy.

PMID- 10956394
TI  - Low-dose tumor necrosis factor-alpha augments antitumor activity of stealth
      liposomal doxorubicin (DOXIL) in soft tissue sarcoma-bearing rats.
AB  - It has previously been demonstrated in the setting of an isolated limb perfusion
      that application of high-dose TNF-alpha in combination with chemotherapy
      (melphalan, doxorubicin) results in strong synergistic antitumor effects in both
      the clinical and preclinical settings. In this study, we demonstrate that
      systemic administration of low-dose TNF-alpha augments the antitumor activity of
      a liposomal formulation of doxorubicin (DOXIL(R)). Addition of TNF-alpha to a
      DOXIL(R) regimen, which by itself induced some tumor growth delay, resulted in
      massive necrosis and regression of tumors. Furthermore, we could demonstrate a
      significant increase of liposomal drug in the tumor tissue when TNF-alpha had
      been co-administered. Administration of TNF-alpha augmented DOXIL(R) accumulation
      only after repeated injections, whereas accumulation of free doxorubicin was not
      affected by TNF-alpha. Drug levels in the tumor interstitium appeared crucial as
      intracellular levels of free or liposome-associated doxorubicin were not
      increased by TNF-alpha. Therefore, we hypothesize that low-dose TNF-alpha
      augments leakage of liposomal drug into the tumor interstitium, explaining the
      observed improved antitumor effects. Regarding the effects of systemic
      administration of low doses of TNF-alpha, these findings may be important for
      enhanced tumor targeting of various liposomal drug formulations.

PMID- 10956395
TI  - Combretastatin A-4 prodrug: a potent inhibitor of malignant hemangioendothelioma
      cell proliferation.
AB  - Anti-vascular treatment by targeting proliferating endothelial cells has become a
      promising option in anti-neoplastic therapy. Combretastatin A-4 prodrug (CA-4PD)
      has been identified as a selective inhibitor of endothelial cell proliferation,
      acting by the interruption of microtubule assembly. In this study, the effect of
      CA-4PD on proliferating endothelial cells derived from a primary tumor of the
      vascular endothelium was investigated in vitro and in vivo. In vitro, CA-4PD was
      an effective inhibitor of endothelial cell proliferation in a time- and dose
      dependent manner, displaying a certain selectivity toward endothelial cells in
      comparison to proliferating fibroblasts. Analysis of DNA profiles by FACS
      revealed an increasing proportion of cells arrested in the G(2) cell-cycle phase
      with correlation to the duration of drug exposure. A decrease in cell viability
      correlated with duration of drug exposure, whereas FACS analysis, DNA
      fragmentation assay, and DNA gel electrophoresis failed to demonstrate that DNA
      fragmentation was indicative of apoptosis up to 48 hr of continued drug exposure.
      In vivo, CA-4PD induced excessive regressive alterations in experimentally
      allotransplanted hemangioendotheliomas within 24 hr after singular i. p.
      injection of 100 mg CA-4PD/kg body weight. This represented less than one-tenth
      of the maximum tolerated dose. In conclusion, our findings characterize CA-4PD as
      a potent inhibitor of malignant endothelial cell proliferation in vitro,
      effecting arrest of proliferating cells in the G(2) cell-cycle phase with
      subsequent cell death on a pathway different from apoptosis. in vivo, CA-4PD
      induces extensive intratumoral cell loss within 24 hr following systemic
      administration, suggesting a synergistic effect of direct cell killing and the
      induction of vascular shutdown.

PMID- 10956397
TI  - Photochemical internalisation increases the cytotoxic effect of the immunotoxin
      MOC31-gelonin.
AB  - Photochemical internalisation (PCI) was recently demonstrated as a unique
      procedure for site-specific delivery of several types of membrane impermeable
      macromolecules from endocytotic vesicles to the cytosol (Berg et al., 1999). The
      technology is based on the cytosolic release of endocytosed macromolecules from
      endosomes and lysosomes upon exposure of cells to photosensitising compounds,
      which became localised to these vesicles, and light. In our study the possibility
      to increase the cytotoxic effect of the immunotoxin MOC31-gelonin by PCI was
      examined. The type I ribosome-inactivating protein gelonin was covalently linked
      to the monoclonal IgG1 antibody MOC31, directed against epithelial glycoprotein-2
      (EGP-2), an antigen expressed on most carcinoma cells. Five different cell lines,
      of which 4 expressed EGP-2, were treated with MOC31-gelonin and endosomal and
      lysosomal localising photosensitisers, followed by exposure to light.
      Insignificant cytotoxicity of the MOC31-gelonin was observed when the cells were
      incubated with the immunotoxin alone. However, in combination with endosomal and
      lysosomal localising photosensitizers, we demonstrate synergistic toxic effect of
      the MOC31-gelonin conjugate in a light-dependent manner. Our results indicate
      that PCI is a promising tool for increasing the cytotoxicity of immunotoxins,
      which is important for further improvement of the PCI concept towards possible
      use in cancer therapy.

PMID- 10956396
TI  - What are the immunologically active components of bacille Calmette-Guerin in
      therapy of superficial bladder cancer?
AB  - The subcomponents of bacille Calmette-Guerin (BCG) involved in the mechanism of
      action of intravesical BCG immunotherapy used for prophylaxis of superficial
      bladder cancer recurrences have been poorly investigated. We purified various BCG
      subcomponents and analyzed in vitro their ability to enhance a Th1 polarized
      immune response as well as to increase lymphocyte-mediated cytotoxicity against
      bladder tumors. Human peripheral blood mononuclear cells (PBMCs) from healthy
      purified protein derivative-positive subjects were incubated for 7 days with
      whole BCG and various fractions (BCG cell wall, plasma membrane, cytosol,
      purified polysaccharides as glucan or arabinomannan, purified native proteins
      from BCG culture filtrate, recombinant 22 kDa protein, phosphate transporter PstS
      2 and -3 proteins). IFN-gamma, IL-12, IL-2, and IL-6 production by stimulated
      PBMCs was compared to unstimulated controls and the phenotype of expanded cells
      analyzed by flow cytometry (FACS analysis). A (51)Cr-release assay monitored the
      cytotoxicity of amplified effector cells against T24 bladder tumor cells. Live
      BCG and most of its subcomponents (with the exception of cytosol, PstS-2 and -3)
      significantly enhanced IFN-gamma and IL-12 secretion, expanded CD3(-)CD56(+)
      cells and the non-MHC-restricted cytotoxicity against bladder tumor cells
      compared to unstimulated controls (all P < 0.001, t-test). IL-2 receptor blockage
      resulted in a clear reduction in the cytotoxic activity of stimulated PBMCs.
      Numerous BCG subcomponents thus provide positive stimuli for Th1 cell
      differentiation and enhance in vitro, non-MHC-restricted cytotoxicity against
      bladder tumor cells. Our findings provide the basis for the therapeutic use of
      several of these subfractions in experimental animal models bearing bladder
      tumors.

PMID- 10956398
TI  - Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and
      thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: a retrospective
      multicenter study.
AB  - Among the methodological approaches of tumor proliferation, thymidine kinase (TK)
      and thymidylate synthase (TS) assays take into account the specific pathways of
      pyrimidine synthesis. Studies pointing to a prognostic value of TK and TS in
      breast cancer involved small numbers of patients. We investigated the prognostic
      value of these enzymes and their combination in a large retrospective multicenter
      study. Nine hundred eight T1T2, N0N1, M0 primary breast cancer samples (median
      follow-up 68 months) were tested. TK and TS were measured in cytosols by using
      standardized radioenzymatic methods. Although a positive correlation was obtained
      between TK and TS (p<10(-5)), major discrepancies were observed in some tumors.
      High levels of both enzymes were associated with large tumor size, histological
      grade III and steroid receptor-negative tumors. Univariate analysis showed that
      TK, TS and their combination were predictive of poor metastasis-free (MFS) (p <
      10(-4); p=0.004; p < 10(-4)) and disease-free survival (DFS) (p < 10(-4);
      p=0.007; p=0.0001). TK was selected as an independent factor for MFS in Cox
      analysis. It was the only variable selected in node-negative patients. Subgroups
      with specific outcomes, with possible therapeutic implications, were identified:
      a) in node-negative patients not receiving adjuvant treatment, TK values in the
      4th quartile were associated with poor MFS (p=0.0002) and DFS (p=0.0005) as
      compared to the other quartiles; b) in node-positive patients receiving adjuvant
      chemotherapy, low levels of both TK and TS were associated with the highest
      survival rates (MFS: p=0.04; DFS: p=0. 03).

PMID- 10956399
TI  - Call and recall for cervical cancer screening in a developing country: a
      randomised field trial.
AB  - A randomised field trial was used to assess Mexican women's response to a mailed
      invitation for a Papanicolaou test. A sample of 4,802 women, 20 to 64 years old,
      chosen at random from the Mexican Social Security Institute Register were
      randomly assigned to an intervention and to a control group. A letter of
      invitation and a reminder were sent to the intervention group. A letter was also
      sent to the control group at the end of the follow-up period (8.5 weeks) in order
      to compare the response among women who received a letter in both groups.
      Cumulative incidence and incidence rates were used to determine the response and
      the speed of response, respectively. The response among women who had received
      the letter was 33.5% (efficacy) in the intervention group, while 5.9% (p<0.001)
      in the control group attended a Papanicolaou test. For the total of women
      invited, the response was 20.1% (effectiveness) and 3.3% (p<0.001), respectively.
      The response was greater in rural areas (rural vs. urban/suburban; p = 0.002) and
      eldest women (50-64 vs. 20-49; p = 0. 02). The response rate was 7 times grater
      in the intervention than in the control group (RR = 7.1; 95% CI 5.4-9.4; p <
      0.001). A mailed invitation to have a Papanicolaou test substantially increases
      attendance by women who receive it. A mailed reminder improves results. This
      strategy could be implemented in addition to the ones already in use, mainly
      among rural and elderly women.

PMID- 10956400
TI  - Rectal cancer and occupational risk factors: a hypothesis-generating, exposure
      based case-control study.
AB  - In 1979, a hypothesis-generating, population-based case-control study was
      undertaken in Montreal, Canada, to explore the association between occupational
      exposure to 294 substances, 130 occupations and industries, and various cancers.
      Interviews were carried out with 3, 630 histologically confirmed cancer cases, of
      whom 257 had rectal cancer, and with 533 population controls, to obtain detailed
      job history and data on potential confounders. The job history of each subject
      was evaluated by a team of chemists and hygienists and translated into
      occupational exposures. Logistic regression analyses adjusted for age, education,
      cigarette smoking, beer consumption, body mass index, and respondent status were
      performed using population controls and cancer controls, e.g., 1,295 subjects
      with cancers at sites other than the rectum, lung, colon, rectosigmoid junction,
      small intestine, and peritoneum. We present here the results based on cancer
      controls. The following substances showed some association with rectal cancer:
      rubber dust, rubber pyrolysis products, cotton dust, wool fibers, rayon fibers, a
      group of solvents (carbon tetrachloride, methylene chloride, trichloroethylene,
      acetone, aliphatic ketones, aliphatic esters, toluene, styrene), polychloroprene,
      glass fibers, formaldehyde, extenders, and ionizing radiation. The independent
      effect of many of these substances could not be disentangled as many were highly
      correlated with each other.

PMID- 10956403
TI  - Response to sunlight and non-Hodgkin's lymphoma, zheng and hansen owens

PMID- 10956401
TI  - Pathology and proliferative activity of renal-cell carcinomas (RCCS) and renal
      oncocytomas in patients with different radiation exposure after the Chernobyl
      accident in Ukraine.
AB  - During the 13-year period subsequent to the Chernobyl accident, the morbidity of
      malignant renal tumors in Ukraine has increased from 4. 7 to 7.5 per 100,000 of
      total population. Cesium 137 ((137)Cs) accounts for 90% of the incorporated
      radioactivity in the Ukrainian population, which has been exposed to long-term,
      low dose ionizing radiation and 90% of the more labile pool of ((137)Cs) is
      excreted via kidneys. The present study was performed to evaluate the
      histopathological features and the immunohistochemical status of proliferating
      cell nuclear antigen (PCNA) and K-ras in renal cell carcinomas (RCCs) of 236
      Ukrainian patients (groups I to V), which represents a varying degrees of
      internal exposure to radiation and were operated in 2 different periods of time
      after the Chernobyl accident. The control group VI of 112 analog patients with
      RCCs was selected in Spain. The strong significant differences between the
      Ukrainian and Spanish groups were found in tumoral nuclear grade, in the
      percentage of sarcomatoid changes, the level of the peritumoral inflammatory
      response as well as in the peritumoral lesions. The dramatic increase of
      aggressivity and proliferative activity supported by strong PCNA and K-ras
      expression of RCCs from Ukrainian groups, associated with chronic radiation
      nephropathy of peritumoral kidney tissue, showed good correlation with the
      duration of radiation exposure and confirmed the influence of chronic but regular
      and sustained low dose of ionizing radiation on renal carcinogenesis of the
      Ukrainian population.

PMID- 10956402
TI  - Sunlight and non-Hodgkin's lymphoma.

PMID- 10956404
TI  - Oncogenic aberrations in the p53 pathway are associated with a high S phase
      fraction and poor patient survival in B-cell Non-Hodgkin's lymphoma.
AB  - The implications of aberrations in the p53 pathway for induction of apoptosis and
      regulation of S phase entry, and for patient survival, were investigated in 83 B
      cell Non-Hodgkin's lymphomas. Eight cases had missense mutations in exons 5, 7, 8
      and 9 as revealed by constant denaturant gel electrophoresis and sequencing.
      Fifteen cases had lost 1 TP53 allele as revealed by fluorescent in situ
      hybridization and comparative genomic hybridization. Ten cases expressed high
      levels of p53 as assessed by immunoblotting and immunohistochemistry. S phase
      fractions were higher, apoptotic fractions were the same and survival times were
      shorter in all aberration groups compared with the cases with no TP53/p53
      aberrations. Since many tumors had more than one TP53/p53 aberration, the tumors
      were divided into groups with the following characteristics: no TP53/p53
      aberrations; loss of one TP53 allele only (9 cases), TP53 point mutation (8
      cases), high-level p53 expression and no TP53 mutation (3 cases). Tumors from the
      3 latter groups had higher median S phase fractions (5%, 7.6%, and 5%,
      respectively, p<0.02) than the cases without any aberrations (1.1%), and survival
      time for these patients was much shorter (relative risks of 5.9, 8.9, and 6.6,
      respectively, p<0.003). Apoptotic fractions were similar in all these groups
      (p=0.09). Multivariate analysis showed that the presence of TP53/p53 aberrations
      is a strong and independent prognostic parameter in B-cell Non-Hodgkin's
      lymphoma.

PMID- 10956405
TI  - Breast cancer risk associated with polymorphism in CYP19 in Japanese women.
AB  - Screening of the entire coding and major promoter regions of the CYP19 gene
      identified two novel polymorphisms at codon 39 (Trp to Arg) and codon 408
      (silent) in addition to those reported previously at codon 264 (Arg to Cys) and
      intron 4 [tetranucleotide (TTTA) simple tandem repeat]. A case-control study was
      conducted in order to see whether or not these polymorphisms were associated with
      breast cancer risk in Japanese women. Homozygous and heterozygous carriers of the
      variant allele Arg at codon 39 showed a significantly decreased risk of breast
      cancer (OR=0.39, 95%C.I.=0. 17-0.89). On the other hand, homozygous carriers of
      the allele with 10 or more TTTA repeats at intron 4 showed a trend toward an
      increase (OR=1.80, 95%C.I.=0.97-3.36) in breast cancer risk. Other polymorphisms
      were found not to be associated with breast cancer risk. These results suggest
      that the CYP19 polymorphisms at exon 39 and intron 4 would be useful for
      selecting Japanese women at a high risk of breast cancer.

PMID- 10956406
TI  - Combined measurement of the c-erbB-2 protein in breast carcinoma tissues and sera
      is useful as a sensitive tumor marker for monitoring tumor relapse.
AB  - c-erbB-2 protein levels in tissue extracts and sera were determined in a
      retrospective analysis of 158 patients who underwent surgical resection of breast
      carcinoma by means of a sandwich enzyme immunometric assay (EIA) using monoclonal
      antibodies (MAbs) directed to the extracellular domain of the c-erbB-2 oncogene
      protein (ErbB-2). In the analysis of tissue extracts, 48 samples (30.3%) showed
      ErbB-2 levels exceeding 18.0 ng/mg protein (group A), while in 110 samples these
      levels were below 18.0 ng/mg protein (group B). Immunohistochemical examination
      of resected tissues using anti-c-erbB-2 antibody revealed positive staining in
      93.8% (45/48) in group A and 13.6% (15/110) in group B (p < 0.00001). The
      proportion of patients who preoperatively showed a serum ErbB-2 value above 5.4
      ng/ml was 52.1% (25/48) in group A and 10.0% (11/110) in group B (p < 0.00001).
      Thus, the level of ErbB-2 in tissue extracts was significantly associated with
      immunohistochemistry and ErbB-2 levels in preoperative sera. During follow-up, 48
      patients (30.3%) developed recurrent disease: 17 in group A (35.4%) and 31 in
      group B (28.2%). From an ROC analysis based on the postoperative serum ErbB-2
      levels in patients either with or without relapse, the cutoff value of serum ErbB
      2 for tumor relapse was determined to be 6.5 ng/ml. The sensitivity of serum ErbB
      2 in patients with relapsed breast cancer was 58.3% (21/36) overall, 84.6%
      (11/13) in group A and 43.5% (10/23) in group B. In the analysis of serum samples
      taken before relapse, 90.9% (10/11) of the subjects in group A and 26.7% (4/15)
      of those in group B were shown to be positive for serum ErbB-2. Serum ErbB-2 in
      group A was a more sensitive marker than other tumor markers such as CEA, CA15-3,
      and NCC-ST-439. Thus, the determination of ErbB-2 in tissue extracts of breast
      carcinoma may be useful for assessing c-erbB-2 protein expression in the primary
      tissue and indicates that serum ErbB-2 may be a sensitive marker for monitoring
      tumor relapse.

PMID- 10956407
TI  - Detection of tumor cells in blood using CD45 magnetic cell separation followed by
      nested mutant allele-specific amplification of p53 and K-ras genes in patients
      with colorectal cancer.
AB  - A new method for detecting circulating tumor cells that is based on magnetic
      activated cell separation (MACS) and nested mutant allele-specific amplification
      (nested MASA) was evaluated in patients with colorectal cancer using the p53 and
      K-ras genes as genetic markers. By negative selection with anti-CD45 monoclonal
      antibody-conjugated supermagnetic microbeads, the proportion of tumor cells was
      enriched 9-fold. By the combination of MACS and nested MASA, 10 tumor cells in
      10(7) normal peripheral blood mononuclear cells could be detected without false
      positives. Using this method, we examined blood taken from the tumor drainage
      veins of 23 patients with colorectal cancer. Eighty-seven percent (20/23) of
      primary tumor tissues showed p53 and/or K-ras gene mutations. Forty-five percent
      (9/20) of patients with p53 and/or K-ras mutations in the primary tumor showed
      the same mutated genes in the blood samples. There was a significant association
      between the presence of p53 and K-ras gene mutation in the blood and tumor size,
      depth of invasion, and venous invasion. Blood gene mutation was detected in 80%
      (4/5) of samples from patients with synchronous liver metastases. Sixty percent
      (3/5) of patients with mutant genes in the blood developed asynchronous liver
      metastases after surgery. The overall survival of patients with p53 and/or K-ras
      gene mutation-positive findings in blood was significantly shorter than that of
      patients testing negative on Kaplan-Meier analysis. Our results suggest that the
      method may be useful for reliable detection of tumor cells circulating in the
      blood and may help to identify patients at high risk for relapse.

PMID- 10956408
TI  - Prognostic significance of the Ca(2+) binding protein S100A2 in laryngeal
      squamous-cell carcinoma.
AB  - We investigated by immunocytochemistry the expression of the Ca(2+) binding
      protein S100A2 in 62 cases of laryngeal squamous-cell carcinoma (SCC). S100A2 was
      detected in 18/19 (95%) low-grade tumors and in 22/43 (51%) high-grade tumors,
      which were partially keratinizing. The remaining 21/43 (49%) high-grade tumors
      were non-keratinizing, anaplastic tumors and clearly S100A2-negative. In normal
      laryngeal squamous epithelium and in laryngeal SCC, S100A2 expression was
      strictly associated with that of cytokeratins 14 (P = 0.0002) and 17 (P =
      0.0021), suggesting an association of S100A2 expression and cell commitment to
      squamous differentiation. A correlation was found between S100A2 tumor positivity
      and longer relapse-free (P = 0.0005) and overall (P = 0.0095) survival.

PMID- 10956409
TI  - Decreased expression of p27 protein is associated with advanced tumor stage in
      hepatocellular carcinoma.
AB  - Reduced expression of the cyclin-dependent kinase inhibitor p27 has previously
      been correlated with fatal clinical outcome in some tumors, including gastric,
      breast, and prostate cancers. For hepatocellular carcinoma, the findings are
      equivocal. In situ hybridization and immunohistochemistry were performed on a
      series of 203 curatively (R0) resected hepatocellular carcinomas and in
      corresponding non-cancerous liver tissue to detect p27. Patients receiving liver
      transplantation were excluded. The results were correlated with histopathological
      stage according to the UICC system, Edmondson grade, several other
      histopathological factors of possible prognostic significance, and finally
      patient survival. Whereas p27 mRNA was expressed homogeneously in all carcinomas
      examined, the p27 protein was found in various amounts. The labeling index of p27
      protein was significantly lower in advanced stages of the disease (P < 0.001,
      chi(2) = 28.1). We observed decreased p27 protein in higher pT categories (P <
      0.001, chi(2) = 24.7) and in multiple tumor nodules (P < 0.001, chi(2) = 9.3).
      Multivariate Cox survival analysis identified age, co-existing cirrhosis, and
      Edmondson grade as independent prognostic factors. We conclude that evaluation of
      p27 in hepatocellular carcinoma is useful to predict stage of disease and may
      have clinical significance, e.g., in predicting optimal therapeutic regimes.

PMID- 10956410
TI  - Distinct clinical features associated with microsatellite instability in
      colorectal cancers of young patients.
AB  - The Hong Kong Chinese population has an unusually high incidence of colorectal
      cancer in the young, suggestive of hereditary susceptibility. To search for a
      genetic basis for this predisposition, we studied the incidence of microsatellite
      instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50
      years old) Chinese colorectal cancer patients referred to the Hong Kong
      Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. By medical record
      review and personal interview, we searched for distinct clinical features
      associated with the manifestation of MSI in this group of patients. For patients
      with MSI tumours, blood was taken for detection of germline mutation in 2
      mismatch repair (MMR) genes. MSI was present in 33 tumours from 23 males and 10
      females (26.6%). Ongoing mutation analysis has so far identified MMR gene
      mutations in 8 patients with MSI tumours. The incidence of MSI increased
      significantly with decreasing age at cancer diagnosis. For patients aged 30 to
      49, MSI tumours were located mainly at the proximal colon. However, for
      exceptionally young patients (<30 years), MSI tumours tended to be at the distal
      large bowel. This observation suggested a differential activity of the MMR
      pathway in colorectal carcinogenesis in different age groups. On multivariate
      analysis, young age at cancer diagnosis, proximal tumour location, a strong
      family history of colorectal cancer, and a personal history of metachronous
      cancer were independent predictors for MSI status. This knowledge may have an
      impact on the management of young colorectal cancer patients and their families.

PMID- 10956411
TI  - Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates
      with prostate carcinoma progression.
AB  - Galectin-3, a member of the beta-galactoside-binding lectin family, is involved
      in a variety of biological events including interactions with galactose
      containing glycoconjugates, cell proliferation, differentiation and apoptosis.
      Galectin-3 appears to intervene during tumor progression and altered expression
      patterns have been reported in a variety of malignancies. In our study, we have
      examined the expression of galectin-3 in a population of 145 prostate carcinoma
      samples using immunohistochemistry. We found that most of the non-tumoral
      prostatic glands exhibited moderate immunostaining for galectin-3 localized in
      both nucleus and cytoplasm. In prostatic cancer cells, galectin-3 was usually not
      expressed or decreased compared with the normal glands. Interestingly, when
      galectin-3 was detected in the cancer cells, it was consistently excluded from
      the nucleus and only present in the cytoplasmic compartment. The latter
      observation was also made for prostatic intraepithelial neoplasia (PIN) cells.
      Furthermore, we found that the levels of galectin-3 expression in the cancer
      cells were significantly associated with prostate-specific antigen (PSA) relapse
      in univariate analysis (p = 0.044). Cytoplasmic expression of galectin-3 in the
      carcinoma cells was an independent predictor of disease progression in
      multivariate analysis, after the pathological stage and the Gleason score. Our
      data demonstrate that galectin-3 is generally down-regulated in human prostate
      carcinoma cells, and consistently excluded from the nucleus. Interestingly,
      specific cytoplasmic expression of galectin-3 in a subset of lesions is
      associated with disease progression. These results suggest that galectin-3 might
      play anti-tumor activities when present in the nucleus, whereas it could favor
      tumor progression when expressed in the cytoplasm. Further studies should
      determine the exact role and mechanisms by which galectin-3 differentially
      affects cell behavior in the different locations where it is expressed.

PMID- 10956412
TI  - Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but
      reside in the cytosol of squamous carcinoma cells.
AB  - An elevation in the circulating level of the squamous-cell carcinoma antigen
      (SCCA) can be a poor prognostic indicator in certain types of squamous-cell
      cancers. Total SCCA in the circulation comprises 2 nearly identical,
      approximately 45 kDa proteins, SCCA1 and SCCA2. Both proteins are members of the
      high-molecular weight serine proteinase inhibitor (serpin) family with SCCA1
      paradoxically inhibiting lysosomal cysteine proteinases and SCCA2 inhibiting
      chymotrypsin-like serine proteinases. Although SCCA1 and SCCA2 are detected in
      the cytoplasm of normal squamous epithelial cells, neither serpin is detected
      normally in the serum. Thus, their presence in the circulation at relatively high
      concentrations suggests that malignant epithelial cells are re-directing serpin
      activity to the fluid phase via an active secretory process. Because serpins
      typically inhibit their targets by binding at 1:1 stoichiometry, a change in the
      distribution pattern of SCCA1 and SCCA2 (i.e., intracellular to extracellular)
      could indicate the need of tumor cells to neutralize harmful extracellular
      proteinases. The purpose of our study was to determine experimentally the fate of
      SCCA1 and SCCA2 in squamous carcinoma cells. Using subcellular fractionation,
      SCCA-green fluorescent fusion protein expression and confocal microscopy, SCCA1
      and SCCA2 were found exclusively in the cytosol and were not associated with
      nuclei, mitochondria, lysosomes, microtubules, actin or the Golgi. In contrast to
      previous reports, metabolic labeling and pulse-chase experiments showed that
      neither non-stimulated nor TNFalpha/PMA-stimulated squamous carcinoma cells
      appreciably secreted these ov-serpins into the medium. Collectively, these data
      suggest that the major site of SCCA1 and SCCA2 inhibitory activity remains within
      the cytosol and that their presence in the sera of patients with advanced
      squamous-cell carcinomas may be due to their passive release into the
      circulation.

PMID- 10956413
TI  - Prognostic implications of microsatellite genotypes in gastric carcinoma.
AB  - Microsatellite alterations such as loss of heterozygosity (LOH) and
      microsatellite instability (MSI) are observed in most (70% to 80%) gastric
      carcinomas. To determine whether the microsatellite genotypes are correlated with
      clinicopathological features, 118 patients with gastric carcinomas were examined
      by using polymorphic microsatellite markers for LOH on 5 gastric cancer
      associated chromosome arms and non-polymorphic BAT markers for MSI.
      Microsatellite genotypes were categorized as high-frequency MSI (MSI-H), high
      level LOH (LOH-H), low-level LOH (LOH-L) and LOH non-detectable (LOH-N). A
      significant fraction of the MSI-H, LOH-H and LOH-L types was observed in
      intestinal-type gastric carcinomas, whereas the LOH-N type was highly associated
      with diffuse-type tumors (p = 0.00162). There was a close relationship between
      microsatellite genotype and TNM (tumor-node-metastasis) stage (p = 0. 001).
      Univariate analysis showed that patients of LOH-H or LOH-N types and those of MSI
      H or LOH-L types correlated with poor and favorable survival, respectively, not
      only in all tumor stages (p = 0.0001) but also in stages II and III (p = 0.0271).
      It is likely that the major genotypes of gastric carcinomas can be placed into at
      least 4 microsatellite categories, thus allowing the construction of a
      comprehensive genetic classification useful for the prediction of diverse
      clinical courses.

PMID- 10956414
TI  - Potential prognostic value of mitogen-activated protein kinase activity for
      disease-free survival of primary breast cancer patients.
AB  - Signaling through pathways involving mitogen-activated protein kinases (MAP
      kinases) has been implicated in the pathogenesis of cancer. Thus, the activity of
      MAP kinase is essential in the malignant potential of human breast tumors.
      p42/44(MAPK) was significantly higher expressed in tumor samples than in matching
      normal tissues adjacent to the tumor. p42/44(MAPK) protein expression correlated
      with enhanced MAP kinase activity only in a subset of tumors, indicating that
      over-expression of MAP kinases does not reflect the activation status of these
      enzymes. MAP kinase activity was significantly elevated in 131 tissue samples
      from primary breast tumors when compared to 18 normal tissues adjacent to tumors.
      A trend for higher MAP kinase activity in primary tumors of node-positive
      patients was observed when compared with tumors from node-negative patients.
      Similarly, higher MAP kinase activities were observed in specimens from patients
      who had a relapse within the follow-up time of 40 months when compared with
      patients with no relapse. A survival analysis demonstrated that the MAP kinase
      activity in primary breast tumors is potentially prognostic for relapse-free
      survival of patients.

PMID- 10956416
TI  - NG2-expressing cells in the central nervous system: are they oligodendroglial
      progenitors?
AB  - Antibodies against the chondroitin sulphate proteoglycan, NG2, are increasingly
      being used to identify the widespread population of oligodendrocyte progenitor
      cells in the adult mammalian CNS. However, the specificity of this marker and the
      role of NG2-expressing cells in CNS function are still open to question. In this
      review we consider the evidence that NG2(+) cells in the CNS are part of the
      oligodendrocyte lineage and whether they can give rise to new oligodendrocytes
      following demyelination. In both the developing and mature rodent CNS, NG2(+)
      cells express the established oligodendrocyte lineage marker PDGF-alphaR and from
      P7, the late progenitor antigen O4, which persists in immature oligodendrocytes.
      They do not express markers of other CNS populations, such as OX42 or GFAP, at
      any developmental age. NG2(+) cells represent the major cycling cell population
      in the normal adult rat CNS, suggesting they have stem cell-like properties. NG2
      immunoreactivity is upregulated as a result of physical, viral, excitotoxic and
      inflammatory insults to the CNS. Following demyelination NG2(+) cell number
      increases in the immediate vicinity of the lesion and rapid remyelination ensues.
      NG2 expression has also been investigated in human tissue. Multi-process bearing
      cells, which morphologically resemble those identified with antibodies against
      O4, persist in chronically demyelinated multiple sclerosis lesions.

PMID- 10956415
TI  - Plasma metalloproteinase activity is enhanced in the euglobulin fraction of
      breast and lung cancer patients.
AB  - Matrix metalloproteinases (MMP) have been implicated in tumor invasion and
      metastasis. We verified, by gelatin zymography, MMP activity in the euglobulin
      plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149
      patients with breast, lung, colon or brain cancer. The euglobulin fractions
      assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md)
      value for 92 kDa-MMP activity was significantly increased in breast (Md 1.34
      arbitrary units [AU]/ml plasma, range 0.0-7.2) and lung cancer patients (Md 1.43
      AU/ml, range 0.0-3.6) compared with the controls (Md 0.48 AU/ml, range 0.0-1.8).
      Patients with colon cancer or gliomas presented values of MMP-9 similar to those
      of the healthy population. Multivariate analysis indicated that plasma MMP-9
      activity was not predicted by the known clinicopathological parameters such as
      age, stage, tumor size, number of positive lymph nodes, histologic grade,
      histologic type, nuclear grade or mitotic index. Lung cancer patients also
      presented high values of MMP-9 (Md 1.43, range 0.0-3.6 [n = 26]), without
      association with tumor stage or histologic type. The levels of 92 kDa-MMP
      activity in the plasma euglobulin fraction could be a potentially useful tumor
      marker in breast and lung cancer.

PMID- 10956417
TI  - Polysialic acid regulates chain formation by migrating olfactory interneuron
      precursors.
AB  - Olfactory interneuron precursors in the rostral migration stream migrate in
      chains and through long distances to the olfactory bulb. The migration is
      inhibited when polysialic acid moiety of NCAM is removed. How polysialic acid
      regulates chain migration has remained unknown. Previous studies in other systems
      have indicated the polysialic acid as a negative regulator of cell-cell
      interactions. Thus, polysialic acid may prevent cells in chains from interacting
      too tightly. To test this hypothesis and examine how polysialic acid regulates
      chain migration, the effect of polysialic acid depletion was evaluated in vitro
      and in vivo. Surprisingly, removal of polysialic acid often resulted in the
      dispersion of chains into single cells in both subventricular zone cultures and
      in adult mice where chain migration was observed. These results indicate that
      polysialic acid plays an important role in the formation of chains by olfactory
      interneuron precursors.

PMID- 10956418
TI  - Conservation of localization patterns of IP(3) receptor type 1 in cerebellar
      Purkinje cells across vertebrate species.
AB  - The distribution of inositol 1,4,5-trisphosphate (IP(3)) receptor type 1
      (IP(3)R1) protein was studied in the adult cerebella of six different vertebrate
      species, zebrafish, skate, claw frog, rat, hamster, and mouse. The receptor was
      found at high expression levels in Purkinje cells in all species examined using a
      subtype-specific polyclonal antiserum against IP(3)R1 and fluorescence
      immunocytochemistry. The immunoreactivity for IP(3)R1 was found intracellularly
      at high concentrations in dendrites and somata and at lower levels in axons of
      these cells. Despite the morphological and functional differences of the
      cerebella the staining patterns of IP(3)R1 labeling in Purkinje cells was
      preserved. This is notable because the cerebella were taken from organisms
      representing a large segment of vertebrate phylogenetic development. The high
      expression levels of IP(3)R1 in Purkinje cells were found independent of the
      degree of the formation of fissures and folia and of the degree of branching of
      Purkinje cell dendrites. The conservation of cerebellar structures not only at
      the cellular level but more importantly at the molecular level suggests that
      identical intracellular calcium signaling mechanisms are used in a number of
      species that represent different areas of phylogenetic development and
      specialization.

PMID- 10956419
TI  - SCO-spondin and RF-GlyI: two designations for the same glycoprotein secreted by
      the subcommissural organ.
AB  - SCO-spondin and RF-GlyI are two designations for cDNAs strongly expressed in the
      bovine subcommissural organ (SCO), characterized, respectively, in 1996 and 1998
      by two different research groups. Because both cDNAs were partial sequences and
      exhibited close similarities in their nucleotide and deduced amino acid
      sequences, it was thought that they might be part of the same encoding sequence.
      To find out, we performed 3'RACE using a SCO-spondin-specific upstream primer.
      From the RT-PCR product generated and by nested PCR techniques, we amplified both
      SCO-spondin and RF-GlyI specific products with the expected length. Also, probes
      generated from both PCR products hybridized to the same major 14 kb transcript in
      Northern blot analyses, clearly showing that SCO-spondin and RF-GlyI cDNAs do
      belong to the same encoding sequence. In addition, we amplified, cloned, and
      sequenced a PCR product of 3 kb spanning both the known SCO-spondin and RF-GlyI
      sequences. The deduced amino acid sequence contains nine thrombospondin type 1
      repeats that alternate with sequences sharing similarities with the D-domain of
      von Willebrand factor. Taken together, these findings show that SCO-spondin and
      RF-GlyI are two designations of the same gene encoding proteins secreted by the
      bovine SCO and forming Reissner's fiber. In addition, compared to the sequence
      provided by Nualart et al. (1998), we extended the reading frame and identified
      new conserved domains in the 3' end of SCO-spondin. The putative function of SCO
      spondin on axonal pathfinding is discussed regarding the presence of a great
      number of thrombospondin type 1 repeats.

PMID- 10956420
TI  - Protein synthesis-dependent but Bcl-2-independent cytochrome C release in zinc
      depletion-induced neuronal apoptosis.
AB  - Previously, we reported that chelation of intracellular zinc with N, N,N',N'
      tetrakis(2-pyridylmethyl)ethylenediamine (TPEN)-induced macromolecule synthesis
      dependent apoptosis of cultured cortical neurons. According to the current theory
      of apoptosis, release of mitochondrial cytochrome C into the cytosol is required
      for caspase activation. In the present study, we examined whether cytochrome C
      release is dependent on macromolecule synthesis. Exposure of cortical cultures to
      2 microM TPEN for 24 hr induced apoptosis as previously described. Fluorescence
      immunocytochemical staining as well as immunoblots of cell extracts revealed the
      release of cytochrome C into the cytosol 18-20 hr after the exposure onset. The
      cytochrome C release was completely blocked by the addition of cycloheximide or
      actinomycin D. Addition of the caspase inhibitor zVAD-fmk did not attenuate the
      cytochrome C release, whereas it blocked TPEN-induced apoptosis. Because Bcl-2
      has been shown to block cytochrome C release potently, we exposed human
      neuroblastoma cells (SH-SY5Y) to TPEN. Whereas Bcl-2 overexpression completely
      blocked both cytochrome C release and apoptosis induced by staurosporine, it
      attenuated neither induced by TPEN. The present results suggest that, in neurons,
      macromolecule synthesis inhibitors act upstream of cytochrome C release to block
      apoptosis and that, in addition to the classical Bcl-2 sensitive pathway, there
      may exist a Bcl-2-insensitive pathway for cytochrome C release.

PMID- 10956421
TI  - Transient oxidative stress in SH-SY5Y human neuroblastoma cells results in
      caspase dependent and independent cell death and tau proteolysis.
AB  - The effects of an oxidative insult on cell survival and tau metabolism were
      investigated in human neuroblastoma SH-SY5Y cells. In this treatment paradigm
      cells were exposed to the membrane permeant oxidant tert-butylhydroperoxide
      (tBHP) for 40 min, returned to fresh media and cell survival/death was monitored
      during the post-treatment period. Cell viability decreased significantly by 6 hr
      after tBHP exposure, and by 24 hr lactate dehydrogenase (LDH) release was 40.1 +/
      8.8% in tBHP treated cells compared to 8.1 +/- 4.7% in control cells. This
      oxidative stress paradigm also resulted in significant activation of caspase-3 by
      2 hr post-treatment and nuclear apoptotic morphology. Furthermore, tBHP treatment
      also resulted in delayed tau proteolysis that was first evident 2 hr post
      treatment. Treatment of the cells with the general caspase inhibitor Boc-Asp(OMe)
      Fluoromethylketone (BAF) completely inhibited caspase-3 activation in response to
      tBHP, and delayed, but did not prevent cell death. BAF treatment also decreased
      tau proteolysis. In vitro, recombinant tau was readily proteolyzed by active
      recombinant caspase-3 into a stable breakdown product. Further tau in the cell
      lysates was cleaved by active recombinant caspase-3 at a rate, and to an extent
      similar to that observed for the well-established caspase-3 substrate poly(ADP
      ribose)polymerase (PARP). These results suggest that oxidative stress-induced
      cell death occurs through both caspase-dependent and-independent pathways, and
      that tau is likely an in situ substrate of caspase-3.

PMID- 10956422
TI  - Long-term culture and characterization of human neurofibroma-derived Schwann
      cells.
AB  - Neurofibromas are benign tumors arising from the peripheral nerve sheath and are
      a typical finding in neurofibromatosis type 1 (NF1). Schwann cells are the
      predominant cell type in neurofibromas and thus are supposed to play a major role
      in the pathogenesis of these tumors. It is not known, however, if NF1 mutations
      in Schwann cells result in an altered phenotype that subsequently leads to tumor
      formation. To characterize the biological properties of neurofibroma-derived
      Schwann cells we developed cell culture techniques that enabled us to isolate
      Schwann cells from neurofibromas and grow them in vitro for several weeks without
      significant fibroblast contamination. Neurofibroma-derived Schwann cells were
      characterized by altered morphology, heterogeneous growth behavior, and increased
      expression of the P0 antigen while several other features of normal human Schwann
      cells were retained. We conclude that neurofibroma-derived Schwann cells exhibit
      a distinct phenotype in vitro but that the observed abnormalities by themselves
      are insufficient to explain neurofibroma formation. Application of our improved
      culture conditions makes neurofibroma-derived Schwann cells readily available for
      further studies to define their role in tumorigenesis in neurofibromatosis type
      1.

PMID- 10956423
TI  - Study of the bidirectional transport of choline by blocking choline carriers from
      outside or inside brain nerve terminals.
AB  - Membrane carriers can operate bidirectionally. We studied, in rat neocortex
      synaptosomes, the choline carrier by comparing the ability of the transport
      inhibitor hemicholinium-3, present outside or inside the nerve terminals, to
      prevent uptake and release of [(3)H]choline. Because hemicholinium-3 is membrane
      impermeable, it was previously entrapped into synaptosomes during homogenization
      of brain tissue. External and internalized hemicholinium-3 produced similar
      maximal inhibition (80-90%) of [(3)H]choline uptake. Also comparable
      (approximately 30 nM) are the potency of externally applied hemicholinium-3 and
      the estimated potency of the entrapped inhibitor. Exposure to ouabain elicited
      release of both [(3)H]acetylcholine and [(3)H]choline from synaptosomes
      prelabeled with [(3)H]choline. The ouabain (300 microM)-evoked release of
      [(3)H]choline only was blocked by externally added (IC(50) approximately 10 nM)
      or internalized (estimated IC(50) approximately 5 nM) hemicholinium-3. Release of
      previously taken up [(3)H]choline elicited by 100 microM external choline
      (homoexchange) was prevented by external (IC(50) approximately 30 microM) or
      entrapped (estimated IC(50) approximately 20 microM) hemicholinium-3. The results
      suggest that the choline carriers fit into the alternating-access model proposed
      for classical transmitter transport. Entrapping nonpermeant ligands into
      synaptosomes could allow investigation of the inward-facing conformation of
      native transporters and how cytoplasmic ligands affect the bidirectional
      transport of neurotransmitters.

PMID- 10956424
TI  - BmK AS: new scorpion neurotoxin binds to distinct receptor sites of mammal and
      insect voltage-gated sodium channels.
AB  - This study was undertaken to assess the binding properties of BmK AS on both
      mammal and insect excitable cell membranes. It was found that BmK AS bound
      specifically to a single class of non-interacting binding sites on both rat brain
      and cockroach nerve cord synaptosomes with high affinity (K(d) = 1.49 +/- 0.14
      and 0.79 +/- 0.29 nM) and low capacity (B(max) = 1.39 +/- 0.09 and 6.60 +/- 1.25
      pmol/mg protein), respectively. Binding kinetics showed that BmK AS could bind
      and reach equilibrium quickly, and dissociate partially from its binding sites on
      both kinds of synaptosomes. The binding of BmK AS was independent of membrane
      potential. Veratridine could not modify the binding of BmK AS. The competitive
      binding assay showed that specific binding of (125)I-BmK AS could be
      significantly inhibited by native BmK AS, BmK AS-1, BmK IT2 and BmK IT on both
      synaptosomes. Unexpectedly, only about 20-30% binding of BmK AS on mammal
      synaptosomes was inhibited by BmK I at 10(-5)-10(-9) M, but not on insect
      synaptosomes. It thus suggests that BmK AS type neurotoxins might bind to a
      distinct receptor site of sodium channels on mammal and insect excitable cell
      membranes with a manner similar to beta-scorpion toxins.

PMID- 10956425
TI  - Is there a relationship between 3-hydroxy-3-methylglutaryl coenzyme a reductase
      activity and forebrain pathology in the PKU mouse?
AB  - Previous reports have suggested that elevated levels of phenylalanine inhibit
      cholesterol synthesis. The goals of this study were to investigate if
      perturbations in cholesterol synthesis exist in the PAH(enu2) genetic mouse model
      for phenylketonuria (PKU), and if so, initiate studies determining if they might
      underlie the white matter pathology that exists in PKU forebrain. Gross sections
      and electron microscopy showed that select tracts were hypomyelinated in adult
      PKU mouse forebrain but not hindbrain. The activity of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMGR), the rate controlling enzyme in the cholesterol
      biosynthetic pathway, was examined in isolated microsomes from forebrain,
      hindbrain, and liver to assess if perturbations in cholesterol biosynthesis were
      occurring. HMGR activity was normal in unaffected PKU hindbrain and was increased
      2-4-fold in PKU liver compared to control. HMGR activity in the forebrain,
      however, was decreased by 30%. Because normal numbers of MBP-expressing glia
      (oligodendrocytes) were present, but the number of glia expressing HMGR was
      reduced by 40% in the hypomyelinated tracts, the decreased HMGR activity seemed
      to result from a down-regulation of HMGR expression in affected oligodendrocytes.
      Exposure of an oligodendrocyte-like glioma cell line to physiologically relevant
      elevated levels of Phe resulted in a 30% decrease in cholesterol synthesis, a 28%
      decrease in microsomal HMGR activity, and a 28% decrease in HMGR protein levels.
      Measurement of HMGR activity after addition of exogenous Phe to control brain
      microsomes revealed that Phe is a noncompetitive inhibitor of HMGR;
      physiologically relevant elevated levels of exogenous Phe inhibited HMGR activity
      by 30%. Taken together, these data suggest that HMGR is moderately inhibited in
      the PKU mouse. Unlike other cell types in the body, a subset of oligodendrocytes
      in the forebrain seems to be unable to overcome this inhibition. We speculate
      that this may be the cause of the observed pathology in PKU brain.

PMID- 10956426
TI  - Huperzine A and tacrine attenuate beta-amyloid peptide-induced oxidative injury.
AB  - Increased oxidative stress resulting from free radical damage to cellular
      function is associated with a number of neurodegenerative diseases, in particular
      with Alzheimer's disease (AD). The deposition of amyloid beta-peptide (Abeta),
      the major pathological hallmark for AD, has been suggested as the central disease
      causing and disease-promoting event for the disease, and the pathological role of
      Abeta was partially mediated by oxidative stress. Here we compared the effects of
      huperzine A (HupA) and tacrine, two acetylcholinesterase (AChE) inhibitors
      available for AD, on Abeta-induced cell lesion, level of lipid peroxidation, and
      antioxidant enzyme activities in rat PC12 and primary cultured cortical neurons.
      Following exposure of both cells to different concentrations of an active
      fragment of Abeta, a marked reduction in cell survival and activities of
      glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased
      production of malondialdehyde (MDA) and superoxide dismutase (SOD), were
      observed. Pretreatment of the cells with HupA or tacrine (0.1-10 microM) prior to
      Abeta exposure significantly elevated the cell survival and GSH-Px and CAT
      activities and decreased the level of MDA. Both drugs have similar protection
      against Abeta insult. Our results indicate that HupA and tacrine exert
      neuroprotective effects against Abeta toxicity, which might be of importance and
      might contribute to their clinical efficacy for the treatment of AD.

PMID- 10956427
TI  - Endogenous generation of cyanide in neuronal tissue: involvement of a peroxidase
      system.
AB  - In a study of the mechanism by which cyanide is produced in neural tissue, it was
      hypothesized that nerve cells generate cyanide in a manner similar to that in
      leukocytes. As in white blood cells, glycine addition enhanced cyanide production
      in rat pheochromocytoma cells. Because myeloperoxidase catalyses cyanide
      production in leukocytes, a selective myeloperoxidase inhibitor (aminobenzoic
      acid hydrazide) was tested and found to inhibit opiate agonist-induced cyanide
      production in pheochromocytoma cells and also in rat brain. In addition, hydrogen
      peroxide enhanced cyanide release in pheochromocytoma cells, further suggesting
      that the process is oxidative in nature. Sonicated rat pheochromocytoma cells did
      not generate cyanide in response to an agonist acting on surface receptors even
      though disrupted cells responded to glycine. The mitochondrial fraction from rat
      brain produced more cyanide in response to glycine than any other fraction. Thus
      glycine seems to act at an intracellular site to enhance cyanide production and
      the process seems to involve a peroxidase mechanism similar to that reported for
      white blood cells.

PMID- 10956428
TI  - Bone cancers in Mayak workers.
AB  - Bone cancer mortality risks were evaluated in 11,000 workers who started working
      at the "Mayak" Production Association in 1948-1958 and who were exposed to both
      internally deposited plutonium and external gamma radiation. Comparisons with
      Russian and U.S. general population rates indicate excess mortality, especially
      among females, plutonium plant workers, and workers with external doses exceeding
      1 Sv. Comparisons within the Mayak worker cohort, which evaluate the role of
      plutonium body burden with adjustment for cumulative external dose, indicate
      excess mortality among workers with burdens estimated to exceed 7.4 kBq (relative
      risk = 7.9; 95% CI = 1.6-32) and among workers in the plutonium plant who did not
      have routine plutonium monitoring data based on urine measurements (relative risk
      = 4.1; 95% CI = 1.2-14). In addition, analyses treating the estimated plutonium
      body burden as a continuous variable indicate increasing risk with increasing
      burden (P < 0.001). Because of limitations in current plutonium dosimetry, no
      attempt was made to quantify bone cancer risks from plutonium in terms of organ
      dose, and risk from external dose could not be reliably evaluated.

PMID- 10956429
TI  - Liver cancers in Mayak workers.
AB  - Liver cancer mortality risks were evaluated in 11,000 workers who started working
      at the "Mayak" Production Association in 1948-1958 and who were exposed to both
      internally deposited plutonium and external gamma radiation. Comparisons with
      Russian liver cancer incidence rates indicate excess risk, especially among those
      with detectable plutonium body burdens and among female workers in the plutonium
      plant. Comparisons within the Mayak worker cohort which evaluate the role of
      plutonium body burden with adjustment for cumulative external dose indicate
      excess risk among workers with burdens estimated to exceed 7.4 kBq (relative risk
      = 17; 95% CI = 8. 0-36) and among workers in the plutonium plant who did not have
      routine plutonium monitoring data based on urine measurements (relative risk =
      2.8; 95% CI = 1.3-6.2). In addition, analyses treating the estimated plutonium
      body burden as a continuous variable indicate increasing risk with increasing
      burden (P < 0.001). Relative risks tended to be higher for females than for
      males, probably because of the lower baseline risk and the higher levels of
      plutonium measured in females. Because of limitations in current plutonium
      dosimetry, no attempt was made to quantify liver cancer risks from plutonium in
      terms of organ dose, and risk from external dose could not be reliably evaluated.

PMID- 10956430
TI  - Pathogenetic process of lung tumors induced by inhalation exposures of rats to
      plutonium dioxide aerosols.
AB  - Sequential examinations were done on the pulmonary cytokinetics and pulmonary
      lesions in rats after inhalation exposure to (239)PuO(2) aerosols to investigate
      the pathogenesis of lung tumors. Total cell yields of lavaged bronchoalveolar
      cells as well as the estimated numbers of pulmonary alveolar macrophages were
      significantly reduced from 1 to 3 months after exposure but recovered thereafter
      to the control levels. The proportions of multinucleated or micronucleated
      pulmonary alveolar macrophages increased significantly in lavaged cells from 1
      month, and the increase was sustained up to 18 months after exposure. Both tumor
      necrosis factor and nitric oxide were shown to be differentially released from
      stimulated cultures of pulmonary alveolar macrophages during the period from 6 to
      18 months after exposure. The labeling indices of alveolar and bronchiolar
      epithelial cells treated with 5-bromo-2'-deoxyuridine increased significantly in
      lungs from 3 months and were sustained up to 18 months after exposure.
      Histopathological examinations revealed that after the early inflammation,
      hyperplasia and metaplasia of the lining of the bronchioloalveolar epithelium
      were predominant from 3 to 6 months, while adenomatous or adenocarcinomatous
      lesions appeared and developed from 12 months after exposure. The appearance of
      primary lung tumors, almost all of which were adenomas and adenocarcinomas, was
      found in the dose range of 1 to 2 Gy from 12 months after exposures. These
      results indicate that the pathogenetic process initiated by early cellular damage
      and alterations associated with inflammation is followed by the proliferative and
      metaplastic lesions of pulmonary epithelium, leading to the appearance and
      development of pulmonary neoplasms from 1 year after the inhalation exposures in
      rats that received a minimum lung dose of more than 1 Gy.

PMID- 10956431
TI  - Dietary sugar beet fiber ameliorates diarrhea as an acute gamma-radiation injury
      in rats.
AB  - Gamma radiation induces diarrhea as an acute injury. We have studied whether
      ingestion of sugar beet fiber influences radiation-induced diarrhea. Abdominal
      irradiation with gamma rays induced diarrhea in male Wistar/ST rats from 2 to 7
      days after a single sublethal dose. The body weight of the irradiated rats was
      decreased temporarily at 4 days after irradiation regardless of the ingestion of
      sugar beet fiber. At day 8, it returned to almost the same level as that of
      unirradiated rats. A change in daily food intake resulted in a pattern similar to
      that for body weight. Dietary sugar beet fiber had little significant effect on
      the changes in body weight and daily food intake, and its ingestion significantly
      decreased gamma-ray-induced diarrhea. Changes in biochemical and histological
      parameters in intestinal mucosa (small intestine, cecum and colon) were not
      greatly influenced by the ingestion of sugar beet fiber through the periods of
      diarrhea. It was concluded that dietary sugar beet fiber ameliorated the diarrhea
      induced by abdominal irradiation. We suggest that the inhibitory effect of the
      ingestion of sugar beet fiber is due to its effects on the luminal environment,
      such as support for bacterial function in the luminal contents in the colon of
      animals that ingest sugar beet fiber.

PMID- 10956432
TI  - Radiation-induced apoptosis in the neonatal and adult rat spinal cord.
AB  - This study was designed to characterize radiation-induced apoptosis in the spinal
      cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10
      week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was
      assessed histologically according to its specific morphological features or by
      using the TUNEL assay. Cell proliferation was assessed immunohistochemically
      using BrdU. Identities of cell types undergoing apoptosis were assessed using
      immunohistochemistry or in situ hybridization using markers for neurons, glial
      progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of
      radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to
      that in the young adult rat spinal cord. A peak response was observed at about 8
      h after irradiation, and the apoptosis index returned to the levels in
      nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated
      increased apoptosis compared to the adult. Values for total yield of apoptosis
      over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly
      greater than that in the adult. Immunohistochemistry studies using Leu7,
      galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein
      indicated that most apoptotic cells were cells of the oligodendroglial lineage
      regardless of the age of the animal. No evidence of Gfap or factor VIII-related
      antigen-positive apoptotic cells was observed, and there was a small number of
      apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat
      spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the
      apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin.
      Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord
      were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in
      the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the
      apoptotic cells were BrdU-positive in 10-week-old rat spinal cord, whereas 62.4
      and 44.1% of the apoptotic cells showed BrdU incorporation in 1- and 2-week-old
      rat spinal cord, respectively. Regardless of the age of the animal, the apoptosis
      indices in BrdU-positive cells were greater than those in BrdU-negative cells. We
      conclude that the neonatal spinal cord demonstrates a greater level of apoptosis
      after exposure to ionizing radiation than the young adult spinal cord. This
      increase in apoptosis may be associated in part with the greater percentage of
      proliferating cells in the neonatal spinal cord, which demonstrate a greater
      level of radiation-induced apoptosis than nonproliferating cells.

PMID- 10956433
TI  - Adaptive response in embryogenesis. III. Relationship to radiation-induced
      apoptosis and Trp53 gene status.
AB  - We reported previously that a radiation-induced adaptive response existed in the
      late period of embryogenesis, and that radiation-induced apoptosis in the
      predigital regions was responsible for digital defects in embryonic ICR mice. To
      investigate the possible involvement of the Trp53 gene and radiation-induced
      apoptosis in radiation-induced adaptive responses in embryogenesis, the present
      study was conducted using Trp53 wild-type (Trp53(+/+)) and Trp53 heterozygous
      (Trp53(+/-)) embryonic mice of the C57BL/6 strain. The existence of a
      radioadaptive response in the Trp53(+/+) embryonic mice was demonstrated by
      irradiating the embryos with 5 or 30 cGy on embryonic day 11 prior to a
      challenging irradiation at 3 Gy on embryonic day 12. The two conditioning doses
      at 5 and 30 cGy significantly suppressed the induction of apoptosis by the
      challenging dose in the predigital regions of limb buds in the Trp53(+/+)
      embryonic mice, while no such effect was found in the Trp53(+/-) embryonic mice.
      These findings indicate that induction of a radioadaptive response in
      embryogenesis is related to Trp53 gene status and the occurrence of radiation
      induced apoptosis.

PMID- 10956434
TI  - Radiation-induced translocations in mice: persistence, chromosome specificity,
      and influence of genetic background.
AB  - The translocation frequency response in the chromosomes of peripheral blood
      lymphocytes is widely used for radiation biomonitoring and dose estimation.
      However, this assay is based upon several assumptions that have not been
      rigorously tested. It is typically assumed that the translocation frequency in
      blood lymphocytes reflects the level of genomic damage in other hemopoietic
      tissues and is independent of the chromosome probe and genetic background. We
      conducted studies to evaluate these assumptions using mice with different genetic
      backgrounds. Six different whole-chromosome fluorescence in situ hybridization
      (FISH) probes were used to detect translocations in peripheral blood lymphocytes
      at multiple times after whole-body irradiation. Translocation frequencies were
      chromosome-independent at 6 and 16 weeks after exposure but were chromosome
      dependent at 1. 5 years after exposure. Similar translocation frequencies were
      observed in blood, bone marrow and spleen at 1.5 years, supporting previous
      suggestions that genetically aberrant peripheral blood lymphocytes may derive
      from precursor populations in hemopoietic tissues. Translocations measured 66 h
      after irradiation differed among some strains. We conclude that the translocation
      frequency response is a complex phenotype that is influenced not only by exposure
      dose but also by genetic background, the choice of chromosome analyzed, and time
      after exposure. These results raise important considerations for the use of the
      FISH-based translocation frequency response for radiation dosimetry and
      biomonitoring.

PMID- 10956435
TI  - Radiation-associated loss of heterozygosity at the Znfn1a1 (Ikaros) locus on
      chromosome 11 in murine thymic lymphomas.
AB  - Although information on the molecular pathways in radiation carcinogenesis is
      accumulating, the data are still relatively scanty. To find the tumor suppressor
      locus associated with radiation carcinogenesis, we determined the frequency and
      distribution of loss of heterozygosity (LOH) of X-ray-induced thymic lymphomas of
      B6C3F(1) mice using 58 microsatellite markers and compared the results with those
      for spontaneous lymphomas and N-ethylnitrosourea (ENU)-induced lymphomas. Based
      on the results, we describe a unique locus with frequent LOH in the centromeric
      region of chromosome 11 of X-ray-induced lymphomas. This locus has never been
      observed to be altered similarly in either ENU-induced or spontaneous lymphomas,
      suggesting radiation-specific molecular alteration. The LOH patterns of
      individual thymic lymphomas indicated that the common region of LOH was located
      within 1.6 cM between D11Mit62 and D11Mit204, a region syntenic to human
      chromosome 7p13. Linkage analysis revealed that the markers of the common LOH
      region were genetically linked to Ikaros (now known as Znfn1a1), a master gene of
      lymphopoiesis. Although the presence of radiation-associated LOH in other loci
      cannot be ruled out, these results suggest a novel molecular pathway in induction
      of thymic lymphomas by ionizing radiation.

PMID- 10956436
TI  - Ex vivo determination of the effect of whole-body exposure to fast neutrons on
      murine spleen cell viability and apoptosis.
AB  - The effects of high-linear energy transfer (LET) radiations on lymphoid tissues
      and lymphocytes are not well understood. As a first approach to delineate these
      effects, the present work was conducted to assess the effects of high-LET
      radiations on murine spleen cells ex vivo and in vitro. BALB/c mice were
      irradiated whole-body with 65 MeV neutrons or 15 MV X rays at doses ranging from
      0.2 to 3 Gy. Spleens were removed 1 day postirradiation and weighed, and single
      cell suspensions were prepared and cultured for several days. Apoptosis occurring
      in vitro was determined at different times by flow cytometry analysis of cells
      labeled with propidium iodide. It was found that irradiation with fast neutrons
      reduced spleen weight and cellularity to a greater extent than photons.
      Considering the spleen cellularity as end point, the relative biological
      effectiveness (RBE) of fast neutrons was 2. However, for both modes of
      irradiation, apoptosis of recovered spleen cells in vitro increased as a function
      of dose and the duration of culture. The level of apoptosis occurring at various
      times postirradiation was found to be identical for high- and low-LET radiations.
      Taken together, these results suggest that external as well as cellular factors
      might differentially modulate the sensitivity of lymphocytes to fast neutrons and
      photons.

PMID- 10956437
TI  - The effectiveness of monoenergetic neutrons at 565 keV in producing dicentric
      chromosomes in human lymphocytes at low doses.
AB  - The induction of dicentric chromosomes in human lymphocytes from one individual
      irradiated in vitro with monoenergetic neutrons at 565 keV was examined to
      provide additional data for an improved evaluation of neutrons with respect to
      radiation risk in radioprotection. The resulting linear dose-response
      relationship obtained (0.813 +/- 0.052 dicentrics per cell per gray) over the
      dose range of 0.0213-0.167 Gy is consistent with published results obtained for
      irradiation with neutrons from different sources and with different spectra at
      energies lower than 1000 keV. Comparing this value to previously published
      "average" dose-response curves obtained by different laboratories for (60)Co
      gamma rays and orthovoltage X rays resulted in maximum RBEs (RBE(m)) of about 37
      +/- 8 and 16 +/- 4, respectively. However, when our neutron data were matched to
      low-LET dose responses that were constructed several years earlier for
      lymphocytes from the same individual, higher values of RBE(m) resulted: 76.0 +/-
      29.5 for (60)Co gamma rays and 54.2 +/- 18.4 for (137)Cs gamma rays;
      differentially filtered 220 kV X rays produced values of RBE(m) between 20.3 +/-
      2.0 or 37.0 +/- 7. 1. The results highlight the dependence of RBE(m) on the
      choice of low-LET reference radiation and raise the possibility that differential
      individual response to low-LET radiations may need to be examined more fully in
      this context.

PMID- 10956438
TI  - Molecular structural analysis of HPRT mutations induced by thermal and epithermal
      neutrons in Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells were exposed to thermal and epithermal
      neutrons, and the occurrence of mutations at the HPRT locus was investigated. The
      Kyoto University Research Reactor (KUR), which has been improved for use in
      neutron capture therapy, was the neutron source. Neutron energy spectra ranging
      from nearly pure thermal to epithermal can be chosen using the spectrum shifters
      and thermal neutron filters. To determine mutant frequency and cell survival,
      cells were irradiated with thermal and epithermal neutrons under three
      conditions: thermal neutron mode, mixed mode with thermal and epithermal
      neutrons, and epithermal neutron mode. The mutagenicity was different among the
      three irradiation modes, with the epithermal neutrons showing a mutation
      frequency about 5-fold that of the thermal neutrons and about 1.5-fold that of
      the mixed mode. In the thermal neutron and mixed mode, boron did not
      significantly increase the frequency of the mutants at the same dose. Therefore,
      the effect of boron as used in boron neutron capture therapy (BNCT) is
      quantitatively minimal in terms of mutation induction. Over 300 independent
      neutron-induced mutant clones were isolated from 12 experiments. The molecular
      structure of HPRT mutations was determined by analysis of all nine exons by
      multiplex polymerase chain reaction. In the thermal neutron and mixed modes,
      total and partial deletions were dominant and the fraction of total deletions was
      increased in the presence of boron. In the epithermal neutron mode, more than
      half of the mutations observed were total deletions. Our results suggest that
      there are clear differences between thermal and epithermal neutron beams in their
      mutagenicity and in the structural pattern of the mutants that they induce.
      Mapping of deletion breakpoints of 173 partial-deletion mutants showed that
      regions of introns 3-4, 7/8-9 and 9-0 are sensitive to the induction of mutants
      by neutron irradiation.

PMID- 10956439
TI  - Reductively activated cleavage of DNA mediated by o, o'-diphenylenehalonium
      compounds.
AB  - o,o'-Diphenylenehalonium (DPH) cations represent a novel class of DNA-affinic
      compounds characterized by binding constants within the range of 10(5)-10(6) M(
      1). The maximum binding capacity of 2-2.5 base pairs per DPH cation and about 30%
      hypochromic reduction in the optical absorption of DPH cations upon binding to
      DNA suggest intercalation as a likely binding mode. In a DNA-bound form, DPH
      cations induce strand breaks upon reduction by radiation-produced electrons in
      aqueous solutions. In keeping with this mechanism, the cleavage is strongly
      inhibited by oxygen and is not affected by OH radical scavengers in the bulk. The
      yields of DPH-mediated base release significantly exceed the yield of base
      release caused by hydroxyl radical (in the absence of scavenger) in anoxic
      solutions. The yields are weakly dependent on DNA loading within the range from 5
      to 50 base pairs per intercalator, which indicates the ability of excess
      electrons in DNA to react with a scavenger separated by tens of base pairs from
      the electron attachment site. The question regarding the mechanism by which the
      distant reactants reach each other in DNA remains unanswered, although it most
      likely involves electron hopping rather than a single-step long-distance
      tunneling. The latter conclusion is based on our finding that the electron
      affinity of DPH cations does not affect their properties as electron scavengers
      in DNA as would be expected if the direct long-distance tunneling is involved.

PMID- 10956440
TI  - Toxicity of DNA-incorporated iodine-125: quantifying the direct and indirect
      effects.
AB  - To understand the biophysical mechanism(s) underlying the induction of cell death
      by the decay of the Auger electron emitter iodine-125 in DNA, Chinese hamster V79
      lung fibroblasts were labeled with 5-[(125)I]iodo-2'-deoxyuridine ((125)IdU) for
      two doubling times and frozen and stored at -135 degrees C in the presence of
      0.26-3.0 M dimethyl sulfoxide (DMSO), which acts simultaneously as a
      cryoprotector and a hydroxyl radical scavenger. After the accumulation of (125)I
      decays, the cells were defrosted and their survival was determined. Within the
      range of the number of decays examined (up to 470 disintegrations per cell), the
      survival curves are exponential. The dependence of the D(37) on DMSO
      concentration is triphasic and seems to reach a plateau at approximately 1.3 M.
      By extrapolating to infinite DMSO concentration, we estimate the D(37) for
      maximal hydroxyl radical scavenging to be 411 +/- 36 disintegrations per cell. To
      determine the D(37) in the absence of DMSO, we extrapolate the D(37) curve to
      zero concentration, and a D(37) of 54 +/- 5 disintegrations per cell is obtained.
      The maximal dose modification factor, calculated as the ratio of the D(37) at
      infinite DMSO concentration (i.e. direct effects only) to the D(37) at zero DMSO
      concentration (i.e. direct and indirect effects), is 7.6 +/- 1.0. By inference,
      approximately 90% of the radiotoxic effects of DNA-incorporated (125)I are due to
      indirect mechanisms.

PMID- 10956442
TI  - Maternal disease and neonatal outcome

PMID- 10956441
TI  - Gap junctional intercellular communication is not a major mediator in the
      bystander effect in photodynamic treatment of MDCK II cells.
AB  - Photodynamic treatment (PDT) of confluent MDCK II cells resulted in a noticeable
      clustering of dead cells, consistent with a significant bystander effect.
      Likewise, PDT of cells in microcolonies resulted in an overabundance of
      microcolonies that had responded to the treatment as a single unit, that is, in
      which either all or no cells were dead. Confluent MDCK II cells appeared to
      communicate via gap junction channels, while cells in microcolonies did not.
      Monte Carlo simulation models were fitted to the distributions of dead cells in
      confluent monolayers and in microcolonies. The simulations showed that the degree
      of the bystander effect was higher in microcolonies than in confluent cells,
      suggesting that gap junction communication may be involved in the bystander
      effect. However, when the gap junction hypothesis was tested by treatment of
      microcolonies with 30 microM dieldrin, an inhibitor of gap junctional
      intercellular communication, there was no reduction of the bystander effect,
      indicating that this effect was not mediated by gap junctional intercellular
      communication. PDT influenced phosphorylation of tyrosine residues in several
      proteins in the cells. Protein phosphorylation is important in cellular signaling
      pathways and may be involved in the bystander effect, for example by influencing
      the mode of cell death.

PMID- 10956444
TI  - Current issues in maternal and perinatal tuberculosis: impact of the HIV-1
      epidemic.
AB  - Human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) are among the
      leading causes of disability and death in the developing world, the largest
      burden borne by sub-Saharan Africa and Asia. Both diseases are significant among
      women of childbearing age, and TB, although uncommon in pregnancy, is on the
      increase. While earlier reports were contradictory regarding the effect of TB on
      the course of pregnancy and vice versa, the negative impacts of each on the other
      have been documented, some in relation to HIV-1 co-infection. This review focuses
      on emerging data on maternal and perinatal TB within the context of HIV-1
      infection.

PMID- 10956443
TI  - HIV in pregnancy: strategies for management.
AB  - HIV/AIDS is now the leading cause of mortality in Africa. Measures for preventing
      HIV infection in women are central to any strategy to manage this disease in
      pregnancy. The use of anti-retrovirals (ARVs) has reduced vertical transmission
      in industrialized countries by about two-thirds. Recent ARV trials in developing
      countries reveal relative efficacies at 6 months of about 40% in breast feeding
      and 50% in non-breast feeding populations. New data on breast feeding adds to the
      information on the pathogenesis of postnatal transmission and can influence
      feeding recommendations. Strategies suitable and inappropriate for developing
      countries, and operational difficulties, are discussed.

PMID- 10956445
TI  - Maternal and neonatal outcome in early- and late-onset pre-eclampsia.
AB  - Early-onset pre-eclampsia and late-onset pre-eclampsia, by virtue of their
      unpredictable nature and prediliction for multi-organ involvement, are associated
      with substantial maternal and fetal morbidity and mortality. Recent years have
      seen the introduction of the concepts of care in specialized units, expectant
      management of pre-eclampsia, conservative management of the HELLP syndrome
      (haemolysis, elevated liver enzymes, low platelets), usage of magnesium sulphate
      and improved feto-maternal surveillance. It is important to note that these
      factors also influence maternal and neonatal outcome.

PMID- 10956446
TI  - Maternal nutrition and fetal growth: practical issues in international health.
AB  - The relationship between maternal nutrition and fetal growth is more complex than
      might be at first assumed. Low birthweight (LBW) increases the risk of early
      mortality and later morbidity, and attempts to improve fetal outcome in
      developing countries need to address the problem of compromised fetal growth.
      This paper examines the links between birthweight and women's nutritional status
      in both biomedical and programmatic contexts.

PMID- 10956447
TI  - Maternal diabetes and neonatal outcome.
AB  - The new definitions and classification of diabetes is discussed. An electronic
      literature search was done especially for randomized trials in management of
      maternal diabetes. However, because of the paucity of such trials the modern
      management we propose is still based on evaluative and retrospective evidence.
      Problems of type 2 diabetes specifically in the developing world are highlighted.
      Although the goals of the St Vincent declaration are attainable; in a practical
      setting (even in excellent centres) we fall far short of achieving perinatal
      mortality and fetal anomaly rates equivalent to the non-diabetic pregnant
      population. This is mainly due to lack of excellent pre-conceptional care for the
      future diabetic mother.

PMID- 10956448
TI  - Perinatal complications associated with maternal tobacco use.
AB  - The use of tobacco products by pregnant women is associated with placenta previa,
      abruptio placentae, premature rupture of the membranes, preterm birth,
      intrauterine growth restriction and sudden infant death syndrome. Approximately
      15-20% of women smoke during pregnancy. It has been suggested that smoking is
      responsible for 15% of all preterm births, 20-30% of all infants of low
      birthweight, and a 150% increase in overall perinatal mortality. Cigarette
      smoking is one of the most important and modifiable risk factors associated with
      adverse perinatal outcomes.

PMID- 10956449
TI  - Alcohol in pregnancy and neonatal outcome.
AB  - Fetal alcohol syndrome (FAS) and other fetal alcohol effects in children are
      characterized by life-long compromises in growth, health, behaviour and cognitive
      ability. Most of the structural signs and many behavioural signs of FAS are
      evident at birth. This review describes the expression of fetal alcohol effects
      in neonates, including diagnostic criteria, alcohol withdrawal, pregnancy
      outcome, growth retardation, facial dysmorphology and behavioural outcomes.

PMID- 10956450
TI  - Sexually transmitted infections, adverse pregnancy outcome and neonatal
      infection.
AB  - Prevention and treatment of sexually transmitted infections (STIs) in the
      sexually active population are the main steps to prevent perinatal infection.
      However, the spread of STIs continues at an astronomical pace despite various
      attempts at controlling the epidemic. An important reason for this lack of STI
      control is that a large percentage of infected people go untreated because they
      have asymptomatic or unrecognized infections. The microbial differential
      diagnosis of STIs implicated in adverse pregnancy outcome is broad and includes
      viral, bacterial and protozoal infections. Infertility, ectopic pregnancy, pelvic
      inflammatory disease, chorioamnionitis, premature rupture of membranes, preterm
      birth and puerperal sepsis are some of complications seen in women as a result of
      infection with sexually transmitted pathogens. In addition, STIs may facilitate
      the acquisition and transmission of HIV. In the fetus or neonate, complications
      include abnormalities of the major organ systems. Infections in the form of
      pneumonia or conjunctivitis may also occur. Due to the lack of simple,
      inexpensive and sensitive point-of-care tests, screening for STIs in pregnancy is
      not performed routinely.

PMID- 10956451
TI  - Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth
      factor receptor: 4-(Phenylamino)quinazoline- and 4-(Phenylamino)pyrido

PMID- 10956452
TI  - Zirconium tetrachloride-formaldehyde sigma-complexes: A computational and
      spectroscopic investigation
AB  - We have carried out a combined theoretical-experimental study of the structures
      and energies of ZrCl(4)-aldehyde complexes using (13)C NMR spectroscopy and a DFT
      (B3LYP) computational approach. The computational investigation has demonstrated
      the existence of different types of complexes: a 1:1 complex (H(2)CO-ZrCl(4)),
      various 2:1 complexes ((H(2)CO)(2)-ZrCl(4)), and several dimeric species. The
      analysis of the energies involved in the formation of the various complexes has
      indicated that the dimeric species should correspond to the only adduct observed
      in the (13)C NMR spectra (carbonyl resonance at 226.96 ppm) when a 1:1
      ZrCl(4)/aldehyde molar ratio is used, while the 2:1 complex should be responsible
      for the signal at 224.30 ppm that is recorded when this molar ratio is 1:2.

PMID- 10956453
TI  - Preparation of 4-substituted benzyl sulfoxylates and related chemistry
AB  - Preparation of dibenzyl sulfoxylate 7a and 4-substituted benzyl sulfoxylates (7b,
      4-NO(2); 7c, 4-Cl; 7d, 4-CH(3)O, 7e: 4-CH(3)) are reported. The unexpected
      stability of 7b has permitted the first X-ray determination at room temperature
      of a sulfoxylate. The thermal isomerization of sulfoxylates 7b-c to sulfinates 8b
      c was studied in different solvents (toluene-d(8), CDCl(3), and CD(3)CN) and
      interpreted as a concerted unimolecular process following first-order kinetics.

PMID- 10956454
TI  - Synthesis of fischer-type (Alkoxy)carbene complexes using diphenylsulfonium salts
      with functionalized alkyl groups
AB  - A new and general method for preparing Fischer-type alkoxycarbene complexes 1 is
      reported. This method involves the alkylation of acylate complexes 7 with
      alkyldiphenylsulfonium salts 10 with a variety of functionalized alkyl groups.
      The alkylation of tetramethylammonium pentacarbonyl(1-oxyalkylidene)chromate(0)
      7a-c, tetramethylammonium pentacarbonyl(1-oxymethylidene)molybdate(0) 7d, and
      pentacarbonyl(1-oxymethylidene)tungstate(0) 7e with alkyldiphenylsulfonium salts
      10 proceeded smoothly under mild conditions to give the corresponding
      alkoxycarbene complexes 12-39 in good to high yields. Competitive alkylation of
      7a with methyl-11 and isopropyldiphenylsulfonium tetrafluoroborate 40 shows a
      higher reactivity of the isopropyl group, suggesting the participation of an S-O
      sulfurane intermediate 41.

PMID- 10956455
TI  - Novel tert-butyl migration in copper-mediated phenol ortho-oxygenation implicates
      a mechanism involving conversion of a 6-hydroperoxy-2,4-cyclohexadienone directly
      to an o-quinone
AB  - Copper mediated ortho-oxygenation of phenolates may proceed through the
      generation of a 6-peroxy-2,4-cyclohexadienone intermediate. To test this theory,
      we studied the fate of sodium 4-carbethoxy-2, 6-di-tert-butylphenolate, where the
      ortho-oxygenation sites are blocked by tert-butyl groups. Using the Cu(I) complex
      of N, N-bis(2-(N-methylbenzimidazol-2-yl)ethyl)benzylamine, isolation of the
      major oxygenated product and characterization by single-crystal X-ray
      crystallography and NMR spectroscopy revealed it to be 4-carbethoxy-3,6-di-tert
      butyl-1,2-benzoquinone, resulting from a 1, 2-migration of a tert-butyl group.
      The independently prepared 6-hydroperoxide is transformed by the Cu(I)- (or
      Cu(II)-) ligand complex to the same o-quinone. The observed 1,2-migration of the
      tert-butyl group appears to reflect an electron demand created by rearrangement
      of the postulated peroxy intermediate. A mechanism proceeding alternatively
      through a catechol and subsequent oxidation to the o-quinone seems ruled out by a
      control study demonstrating that the requisite intermediate to catechol formation
      would instead eliminate the 2-tert-butyl group.

PMID- 10956456
TI  - New chiral phosphine-phosphite ligands in the enantioselective palladium
      catalyzed allylic alkylation
AB  - A series of chiral phosphine-phosphite ligands 1-6 have been synthesized and used
      in the enantioselective palladium-catalyzed reaction of rac-1,3-diphenyl-2
      propenyl acetate with dimethyl malonate as nucleophile. Ligands 1a, 2, 3, 5a, 6a,
      and 6b have been synthesized starting from racemic tert
      butylphenylphosphinoborane. The use of dynamically resolved Li phosphide (-)
      sparteine provided the optically pure ligands. Crystals of the allylpalladium
      (6a) complex were obtained, suitable for X-ray crystal structure determination.
      The X-ray crystal structure of the allylpalladium (6a) complex revealed a longer
      palladium-carbon bond distance trans to the phosphine moiety indicating that the
      attack of the nucleophile takes place at the carbon trans to the phosphine
      moiety. This was confirmed by the fact that the phosphine moiety did not affect
      the enantioselectivity directly. Under mild reaction conditions,
      enantioselectivities up to 83% were obtained (25 degrees C) with ligand 1e.
      Systematic variation of the ligand bridge and the phosphite moiety showed that
      the configuration of the product is controlled by the atropisomerism of the
      biphenyl substituent at the phosphite moiety. The conformation of the biphenyl
      group, in turn, is controlled by the substituent at the chiral carbon in the
      bridge. Ligands with large bite angles yielded higher enantioselectivities.

PMID- 10956457
TI  - Concept of improved rigidity: how to make enantioselective hydrophosphonylation
      of cyclic imines catalyzed by chiral heterobimetallic lanthanoid complexes almost
      perfect
AB  - The catalytic and enantioselective hydrophosphonylation of cyclic imines using
      cyclic phosphites is described for the first time. In contrast to the application
      of acyclic phosphites, significant improvements are presented arising from the
      concept of improved rigidity by utilization of cyclic phosphites in the
      lanthanoid BINOL complex catalyzed hydrophosphonylation of 3-thiazolines. Cyclic
      phosphites are shown to provide certain improvements within the catalytic cycle.
      Influence of parameters such as concentration of the catalyst and the phosphite
      on the catalysis is examined as well as the effects of the substituents on the
      starting material. The pharmacologically interesting thiazolidinyl phosphonates
      are synthesized in excellent optical purities of up to 99% ee and high chemical
      yields of up to 99%. The required amount of catalyst is reduced to 2.5 mol %. The
      highest efficiency of the reaction involving cyclic phosphites is achieved using
      the catalytic system "2.5 mol % (S)-YbPB/2.5 equiv phosphite/50 degrees C/48
      h/THF-toluene (1:7)". On the basis of the results a refinement of the proposed
      catalytic cycle has been provided. For comparison cyclic phosphites were used in
      hydrophosphonylation with a chiral titanium catalyst.

PMID- 10956458
TI  - Iodocyclization of O-(3-Cyclohexenyl)thiocarbamidates. An unexpected approach to
      vicinal cis-aminocyclohexenols
AB  - An unprecedented and unexpected iodocyclization of O-(3
      cyclohexenyl)thiocarbamidates 2a-c to diiodides 7a-c, followed by alkaline
      hydrolysis and iodide elimination, has uncovered an alternative approach to
      vicinal cis-aminocyclohexenols 10a-c and 11a-c. This represents a new approach to
      these interesting building blocks.

PMID- 10956459
TI  - Fluorination of thiocarbonyl compounds with Bis(2-methoxyethyl)aminosulfur
      trifluoride (Deoxo-fluor reagent): A facile synthesis of gem-difluorides
AB  - A variety of thiocarbonyl derivatives (thioketone, thioester, thioamide,
      dithioester, and dithiocarbamate) were converted to the corresponding gem
      difluorides in excellent yields on reaction with the fluorinating agent, bis(2
      methoxyethyl)aminosulfur trifluoride, in the presence of SbCl(3).

PMID- 10956461
TI  - Polymeric reagents with propane-1,3-dithiol functions and their precursors for
      supported organic syntheses
AB  - Reliable completely odorless syntheses of soluble copolymeric reagents of styrene
      type containing propane-1,3-dithiol functions able to convert carbonyl compounds
      into 1,3-dithiane derivatives and to support other useful transformations are
      reported together with their progenitor copolymers containing benzenesulfonate or
      thioacetate groups perfectly stable in open air and suitable for unlimited
      storage. The effectiveness of the prepared reagents as tools for polymer
      supported syntheses to produce ketones by aldehyde umpolung and alkylation is
      tested in the conversion of benzaldehyde to phenyl n-hexyl ketone starting from
      copolymers with different contents of active units and molecular weights. To
      facilitate the adaptation of the prepared soluble copolymeric reagents to other
      possible applications, a table of solvents and nonsolvents is presented.

PMID- 10956460
TI  - Total synthesis of the siderophore danoxamine.
AB  - The total synthesis of the linear trihydroxamate siderophore, Danoxamine, is
      described. Danoxamine is a siderophore component of the naturally occurring
      siderophore-drug conjugates Salmycin A-D. The synthesis of Danoxamine features a
      series of coupling reactions involving N-(5-benzyloxypentyl)-O
      benzylhydroxylamine being linked by a succinoyl linker to N-(benzyloxy)-1,5
      pentanediamine. Two more succinoyl linkers and another N-(benzyloxy)-1,5
      pentanediamine were used in coupling reactions to afford the fully protected
      siderophore. The linear tetrabenzyl-protected trihydroxamate was deprotected to
      afford the natural product Danoxamine.

PMID- 10956462
TI  - Mangicols: structures and biosynthesis of A new class of sesterterpene polyols
      from a marine fungus of the genus Fusarium.
AB  - A marine fungal isolate, tentatively identified as Fusarium heterosporum, has
      been found to produce a series of structurally novel sesterterpene polyols, the
      mangicols A-G (4-10). The structures of the new compounds, including the
      stereochemistry of mangicol A, were assigned by interpretation of spectral data
      derived from both natural products and synthetic derivatives. The mangicols,
      which possess unprecedented spirotricyclic skeletal components, show only weak to
      modest cytotoxicities toward a variety of cancer cell lines in in vitro testing.
      Mangicols A and B, however, showed significant antiinflammatory activity in the
      PMA (phorbol myristate acetate)-induced mouse ear edema model. A biosynthetic
      pathway for the neomangicol and mangicol carbon skeletons is proposed on the
      basis of the incorporation of appropriate radiolabeled precursors.

PMID- 10956463
TI  - Acid-promoted reactions of ethyl linoleate with nitrite ions: formation and
      structural characterization of isomeric nitroalkene, nitrohydroxy, and novel 3
      nitro-1,5-hexadiene and 1,5-dinitro-1, 3-pentadiene products.
AB  - The reaction of ethyl linoleate (1) with NO(2)(-) in different air-equilibrated
      acidic media resulted in the formation of complex patterns of products, some of
      which could be isolated by repeated TLC fractionation and were formulated as the
      nitroalkenes 2-5, the novel (1E, 5Z)-3-nitro-1,5-hexadienes 6/7, the novel (E,E)
      1, 5-dinitro-1,3-pentadiene derivatives 8 and 9, and the nitro alcohols 10/11 and
      12/13 by extensive GC-MS and 2D NMR analysis, as aided by 1D Hartmann-Hahn proton
      mapping experiments. Similar reaction of methyl oleate gave mainly nitroalkene
      (14/15) and allylic nitro derivatives (16/17). Formation of 2-13 may be envisaged
      in terms of HNO(2)-mediated nitration pathways in which regioisomeric beta
      nitroalkyl radical intermediates derived from attack of NO(2) to the 1,4
      pentadiene moiety of 1 evolve through competitive H-atom abstraction and free
      radical combination routes.

PMID- 10956464
TI  - Diels-alder adducts of 5-alkynylcyclopentadienols with tetracyanoethylene and
      dimethyl acetylenedicarboxylate: An X-ray crystallographic study of unexpected
      rearrangement products
AB  - The Diels-Alder reaction of tetracyanoethylene (TCNE) with 1, 4-diethyl-5
      (trimethylsilyl)ethynyl-2,3-diphenylcyclopentadien-5-ol (3a) occurs on the
      hydroxyl-bearing face of the diene and yields ultimately an imino lactone (5a),
      whereby the hydroxyl functionality has added across an exo nitrile linkage. TCNE
      and 5-(trimethylsilyl)ethynyl-1,2,3,4-tetraphenylcyclopentadien-5-ol (3b) behave
      analogously. In contrast, the [4 + 2] adduct of 3b with dimethyl
      acetylenedicarboxylate (DMAD) undergoes a dramatic skeletal rearrangement to
      generate the 1,4-cyclohexadiene (9) in which an alkynyl ketone moiety has
      migrated onto an ester-bearing carbon. The molecules 5a and 9 have been
      characterized by X-ray crystallography, and a mechanism for the skeletal
      rearrangement is proposed.

PMID- 10956465
TI  - Construction of the Tricyclo
AB  - Histrionicotoxin derivatives have long been attractive targets for synthetic
      chemists as a result of their useful neurophysical properties, low natural
      abundance, and the unique structural features of the azaspiro[5.5]undecane ring
      system. Utilizing our tandem pinacol rearrangement-ene strategy and regiospecific
      Baeyer-Villiger oxidation as key steps, we have successfully synthesized an
      advanced synthetic intermediate, spiro[5.4]decane 4, which has previously been
      converted to (+/-)-perhydrohistrionicotoxin (5b). Pinacol rearrangement of simple
      Diels-Alder derived bicyclo[2.2.2]octene system 2a, followed by an ene reaction,
      led to the efficient formation of the highly fuctionalized
      tricyclo[5.3.1.0(1,5)]undecane system 1a. This tricyclic system 1a was
      selectively transformed into spiro[5. 4]decane system 4 via a regiospecific
      Baeyer-Villiger oxidation reaction. We also report the results of systematic
      studies of Baeyer-Villiger oxidation reactions of tricyclo[5.3.1.0(1,
      5)]undecanone systems to elucidate the origin of the regioselectivity of this
      process.

PMID- 10956466
TI  - All eight stereoisomeric D-glyconic-delta-lactams: synthesis, conformational
      analysis, and evaluation as glycosidase inhibitors.
AB  - An efficient and general synthetic route to all eight stereoisomeric D-glycono
      delta-lactams has been developed. The strategy involves, as a key step, a
      stereodivergent delta-lactam formation with configurational retention or
      inversion at C-4 of a starting gamma-lactone to lead to two epimers of delta
      lactam from one parent gamma-lactone. Conformations of eight glycono-delta
      lactams were examined by X-ray crystallographic analysis and molecular modeling.
      Analyses of conformation and glycosidase-inhibition provide useful information
      for the design of new glycosidase inhibitors.

PMID- 10956467
TI  - Attractive through-space S-O interaction in the DNA-cleaving antitumor antibiotic
      leinamycin.
AB  - We describe here a study on the intramolecular nonbonded 1, 5-sulfur-oxygen (S-O)
      interaction in the antitumor antibiotic leinamycin 1. The results from density
      functional theoretical and semiempirical calculations on leinamycin 1 and model
      systems 2-5 provide evidence for the 1,5-S-O nonbonded interaction. Our results
      are used to explain previous experimental data on the X-ray structure of
      leinamycin 1 (Hirayama, N.; Matsuzawa, E. S. Chem. Lett. 1993, 1957). The amide
      oxygen (O5) alters the thiosulfinate ester conformation and stabilizes the 1,2
      dithiolan-3-one 1-oxide heterocycle. The attractive interaction induces S1 of
      leinamycin to adopt a distorted trigonal bipyramidal geometry. The magnitude of
      this stabilizing interaction is approximately 6 kcal/mol.

PMID- 10956468
TI  - Stereoselective synthesis of CF(2)-substituted phosphothreonine mimetics and
      their incorporation into peptides using newly developed deprotection procedures.
AB  - Stereoselective syntheses of all four stereoisomers of CF(2)-substituted
      nonhydrolyzable phosphothreonine derivatives (33, 39, and their enantiomers) and
      their incorporation into peptides are described herein. Key to the synthesis of
      these amino acids was construction of secondary phosphate-mimicking
      difluoromethylphosphonate units along with generation of two stereocenters. The
      former was achieved using a Cu(I)-mediated cross-coupling reaction of
      BrZnCF(2)P(O)(OEt)(2) (8) and beta-iodo-alpha,beta-unsaturated ester 12, with
      stereochemistry of both alpha- and beta-stereocenters being established using
      bornane-10,2-sultam as a chiral auxiliary. Diastereoselective hydrogenation of a
      chiral alpha,beta-unsaturated acylsultam (for the beta-center) (e.g., 16a) and
      subsequent stereoselective bromination (for the alpha-center of the threo
      derivative) or amination (for the alpha-center of erythro (allo) derivative) were
      utilized. Transesterification of the bromide to the benzyl ester followed by
      azide displacement of the halogen, then reduction of the resulting azide,
      followed by Boc-protection and finally removal of the benzyl group, afforded
      protected both L- and D-phosphothreonine mimetics (39 and its enantiomer). On the
      other hand, protected both L- and D-allo-phosphothreonine mimetics (33 and its
      enantiomer) were synthesized via transesterification of the above-mentioned
      amination product, followed by hydrogenolytic removal of the benzyl group. Key to
      utilization of these amino acid analogues in peptide synthesis was removal of
      ethyl protection from the difluoromethylphosphonate moiety. A two-step
      deprotection methodology, consisting of a combination of a first-step reagent
      [0.3 M BSTFA-TBAI in CH(2)Cl(2), BF(3).Et(2)O] followed by a second-step reagent
      [1 M TMSOTf-thioanisole in TFA, m-cresol, EDT] was developed for use in solid
      phase protocols. A 12-residue Cdc (cell division cycle) 2-peptide 41, possessing
      two nonhydrolyzable phosphoamino acid mimetics (F(2)Pmab 6 and F(2)Pmp 4), was
      subjected to this deprotection procedure and was obtained in 25% yield based on
      the protected resin. The present synthetic method affords nonhydrolyzable
      phosphoamino acid mimetics-containing peptides in high yield without accompanying
      side reactions.

PMID- 10956469
TI  - Efficient conjugation of peptides to oligonucleotides by "native ligation".
AB  - A new strategy has been developed for conjugation of peptides to
      oligonucleotides. The method is based on the "native ligation" of an N-terminal
      thioester-functionalized peptide to a 5'-cysteinyl oligonucleotide. Two new
      reagents were synthesized for use in solid-phase peptide and oligonucleotide
      synthesis, respectively. Pentafluorophenyl S-benzylthiosuccinate was used in the
      final coupling step in standard Fmoc-based solid-phase peptide assembly.
      Deprotection with trifluoracetic acid generated in solution peptides substituted
      with an N-terminal S-benzylthiosuccinyl moiety. O-trans-4-(N-alpha-Fmoc-S-tert
      butylsulfenyl-L-cysteinyl)aminoc yclohe xyl O-2-cyanoethyl-N,N
      diisopropylphosphoramidite was used in the final coupling step in standard
      phosphoramidite solid-phase oligonucleotide assembly. Deprotection with aqueous
      ammonia solution generated in solution 5'-S-tert-butylsulfenyl-L-cysteinyl
      functionalized oligonucleotides. Functionalized peptides and oligonucleotides
      were used without purification in native ligation conjugation reactions in
      aqueous/organic solution using tris-(2-carboxyethyl)phosphine to remove the tert
      butylsulfenyl group in situ and thiophenol as a conjugation enhancer. A range of
      peptide-oligonucleotide conjugates were prepared by this route and purified by
      reversed-phase HPLC.

PMID- 10956470
TI  - Stereospecific thermal isomerization of 2, 2-dimethylbenzocyclobutenols to 2
      isopropenylphenyl alcohols
AB  - Thermolysis of the 1-alkyl-2,2-dimethylbenzocyclobutenol 3 at 160 degrees C gave
      the 2-isopropenylphenyl alcohol 8 through an (E)-dienol intermediate by a 1,5
      sigmatropic hydrogen shift from the isopropylidene methyl group to the carbon
      bearing hydroxy group. In the thermolysis of each of the diastereomeric 2, 2
      dimethylbenzocyclobutenols 6 and 7 which have a hydroxy group on the beta-carbon
      of the quaternary C(1)-alkyl substituent, the isomerization to the 2
      isopropenylphenyl alcohols 10 and 11 took place stereospecifically through a
      twisted (E)-dienol intermediate. The configuration of the newly formed chiral
      center in 10 and 11 was the same as that of the ring carbon bearing hydroxy group
      in the starting 6 and 7.

PMID- 10956471
TI  - Ru(II)- and Pt(II)-catalyzed cycloisomerization of omega-aryl-1-alkynes.
      Generation Of carbocationic species from alkynes and transition metal halides and
      its interception by an aromatic ring
AB  - The treatment of aryl-1-alkynes, such as 4-aryl-1-butyne, 5-aryl-1-pentyne, and 6
      aryl-1-hexyne, with catalytic amounts of transition metal chlorides, such as
      PtCl(2) and [RuCl(2)(CO)(3)](2), at 80 degrees C in toluene results in
      cycloisomerization to give dihydronaphthalenes or dihydrobenzocycloheptenes, in
      which the cyclization mode is dependent on the length of the tethers. The
      reaction is limited to substrates containing terminal alkynes. A key step of the
      reaction is the intramolecular interception by an aromatic ring of the vinylmetal
      complex 2, which contains a cation center at the beta-position, generated from
      the electrophilic addition of transition metal halides toward an alkyne. The more
      electron-rich aryl systems are more reactive.

PMID- 10956472
TI  - Synthesis of optically active alpha-methylene beta-lactams through lipase
      catalyzed kinetic resolution.
AB  - A convenient method for the preparation of the hitherto unknown chiral alpha
      methylene beta-lactam derivatives 5a,b is reported. The optically active alpha
      methylene beta-lactams 5a-c, and their corresponding amino acids 6a-c have been
      readily made available through lipase-catalyzed kinetic resolution in high
      enantiomeric purity (up to 99% ee). The N-substituted beta-lactam derivatives 4a,
      b and 10 are not accepted by the lipases and were prepared in optically active
      form by chemical transformation.

PMID- 10956473
TI  - Synthesis of racemic brevioxime and related model compounds.
AB  - The synthesis, in racemic form, of the insect juvenile hormone inhibitor
      brevioxime (1) is described, as well as exploratory studies that led to the
      related model compounds 14 and 15a. The route to 1 involves Ag(+)-mediated
      coupling of the amine derived from 20 with the beta-keto thioester 32. Acid
      treatment of the coupled product 33 led by acetal hydrolysis, cyclization, and
      desilylation to 34a,b, from which 1 was reached by oxidation and conversion into
      the oxime. In the synthesis of the amino component 20, a known, but unusual,
      reduction was used for converting a nitrile into an amine hydrochloride.

PMID- 10956474
TI  - Tandem radical decarboxylation-oxidation of amino acids: A mild and efficient
      method for the generation of N-acyliminium ions and their nucleophilic trapping
AB  - A convenient methodology for the synthesis of 2-substituted pyrrolidines from
      alpha-amino acids is described. A number of cyclic and acyclic alpha-amino acid
      derivatives have been prepared in order to test the scope and
      diastereoselectivity of this method. These substrates were treated with
      iodosylbenzene or (diacetoxyiodo)benzene (DIB) and iodine in order to generate
      the corresponding carboxyl radical, which evolves by loss of carbon dioxide to
      produce a carbon radical which in turn undergoes oxidation to an N-acyliminium
      ion. This postulated intermediate could be trapped inter- or intramolecularly by
      oxygen, nitrogen and carbon nucleophiles. In the case of carbon nucleophiles, a
      Lewis acid is required for the concomitant carbon-carbon bond formation. High
      yields and modest diastereoselectivities were obtained. The present methodology
      was applied to the synthesis of omega-amino aldehydes or hemiaminals 8-14, 2
      aminopyrrolidine derivative 15, aminolactone derivative 16, and azasugar
      analogues 17 and 18. When carbon nucleophiles were used, alkaloid precursors such
      as 2-allyl- or 2-alkylpyrrolidines 19-23 and 25 were obtained.

PMID- 10956475
TI  - 3-Aza-cope rearrangement of quaternary N-allyl enammonium salts. Stereospecific
      1,3 allyl migration from nitrogen to carbon on a tricyclic template
AB  - N-Allyl enamines can undergo a [3,3] sigmatropic rearrangement known as a 3-aza
      Cope (or amino-Claisen) reaction. We explored a 3-aza-Cope reaction involving 1,3
      allylic migration from nitrogen to carbon in N-allyl enammonium quaternary salts,
      exemplified by benzo[a]quinolizine 8 and pyrrolo[2,1-a]isoquinoline 13, with an
      interest in stereochemistry and mechanism. Salts 8 and 13 were accessed,
      respectively, through stereospecific allylation of hydroxy amines 4 and 11a/11b
      to give 7 and 12a/12b, which were dehydrated with trifluoroacetic acid. Allylic
      migration in these tricyclic tetrahydroisoquinolines occurred with high
      stereospecificity, with the major products 9 (from 8) and 15a (from 13)
      apparently deriving from a concerted suprafacial [3,3] rearrangement. The
      rearrangement of 8 to 9 was facile at 23 degrees C (t(1/2) = ca. 5 h) and was
      >98% stereospecific, whereas the rearrangement of 13 to 15a/15b required heating
      between 50 and 100 degrees C, with ca. 90-95% stereospecificity (t(1/2) = ca. 0.3
      h at 100 degrees C). A deuterium-labeling experiment with 21 ((2)H-13) confirmed
      that allylic inversion accompanies the 1,3 migration en route to major isomer 22a
      ((2)H-15a), supporting the predominance of a concerted [3, 3] sigmatropic
      mechanism. However, the 5-10% loss of stereospecificity in the rearrangements of
      the pyrroloisoquinolines 13 and 21, reflected by formation of minor isomers 15b
      and 22b, respectively, indicates a minor nonconcerted reaction pathway.

PMID- 10956476
TI  - Preparation and molecular structures of 9,10-dihydrophenanthrenes: substituent
      effects on the long bond length
AB  - 9,10-Dihydrophenanthrene derivatives 1-3 with electron-donating and/or -accepting
      groups at their 9,10-positions were prepared, and their precise molecular
      structures were determined by X-ray analyses at 203 K. The long C(9)-C(10) bond
      [1.646(4) A] in the hexaarylethane-type compound 1 with four electron-donating
      groups is mainly caused by steric interaction. Push-pull type substitution does
      not induce the elongation of the central bond in the present system; the
      corresponding distance in 9, 9-bis(4-dimethylaminophenyl)-10,10-dicyano
      derivative 2 [1.599(4) A] is intermediate between those of 1 and the tetracyano
      compound 3 [1. 587(2) A].

PMID- 10956477
TI  - Facile and efficient synthesis of 4-azidotetrafluoroaniline: a new photoaffinity
      reagent.
AB  - p-Azidotetrafluoroaniline (1) was synthesized in 65-73% yield by two different
      methods employing a stable carbamate intermediate. The first method trapped the
      intermediate isocyanate generated via a modified Curtius rearrangement with 2
      methyl-2-propanol or 2-(trimethylsilyl)ethanol to form the stable carbamates 2d
      and 2e, respectively. Benzoic acid 2c was first converted to its acid chloride
      with PCl(5). Displacement of the chloride by NaN(3) in acetone/water formed the
      acyl azide. Thermal rearrangement followed by the addition of the appropriate
      alcohols provided the carbamates. The acid labile carbamate 2d was deprotected
      with HCl/AcOH to provide 1, while trifluoroacetic acid was required to deprotect
      2e and afford 1. In the second path, 1 was synthesized in five steps from
      pentafluoronitrobenzene (3a) in 65% overall yield. Compound 3a was converted into
      4-azidotetrafluoronitrobenzene (3b) with NaN(3) in 93% yield and was used without
      further purification to form 1, 4-diaminotetrafluorobenzene (3c) by Sn/HCl
      reduction in 85% yield. The mono-9-fluorenylmethoxycarbonyl (FMOC) derivative 3d
      was formed from 3c with FMOC-Cl and pyridine in EtOAc in 92% yield. Diazotization
      of 3d under anhydrous conditions with TFA/NaNO(2) and NaN(3) gave 3e in 87%
      yield. The aryl azide was formed with concurrent nitration of the 2-position of
      the fluorenyl system. The protecting group was removed with piperidine to afford
      1 in 93% yield. Irradiation of 1 with 254 nm light in cyclohexane gave
      cyclohexylamine 11, diamine 3c, and azobenzene 12 as the primary products. The
      formation of C-H insertion product 11 indicates that 1 forms a singlet nitrene
      upon photolysis. Two heterobifunctional photoaffinity reagents iodoacetamide 9
      and dansyl derivative 10 were prepared.

PMID- 10956478
TI  - Probing furanose ring conformation by gas-phase computational methods: energy
      profile and structural parameters in methyl beta-D-arabinofuranoside as a
      function of ring conformation
AB  - The potential energy surface of methyl beta-D-arabinofuranoside (3) has been
      studied by ab initio molecular orbital (HF/6-31G) and density functional theory
      (B3LYP/6-31G) calculations via minimization of the 10 possible envelope
      conformers. The partial potential energy surface identified that the global
      minimum and lowest energy northern conformer was E(2). In the HF calculations,
      (2)E was the most stable southern conformer, while the density functional theory
      methods identified (4)E as the local minimum in this hemisphere. Additional
      calculations at higher levels of theory showed that the B3LYP-derived energies of
      many of the envelope conformers of 3 are dependent upon the basis set used. It
      has also been demonstrated that B3LYP/6-31+G//B3LYP/6-31G single point energies
      are essentially the same as those obtained from full geometry optimizations at
      the B3LYP/6-31+G level. The northern and southern minima of the B3LYP/6-31+G
      surface are, respectively, the E(2) and (2)E conformers. The B3LYP/6-31G
      geometries were used to study the relationship between ring conformation and
      various structural parameters including bond angles, dihedral angles, bond
      lengths, and interatomic distances.

PMID- 10956479
TI  - Structural factors for the formation of propellane-type products in the
      solvolysis of bicyclic bridgehead compounds
AB  - Methanolyses of 2-oxobicyclo[3.3.1]non-1-yl triflate, 3, 3-dimethyl-2
      oxobicyclo[3.3.1]non-1-yl triflate, and 2-oxobicyclo[4. 3.1]dec-1-yl mesylate
      gave the corresponding propellanone in 12%, 20%, or 3.2% yield, respectively,
      beside substitution or rearranged products under typical conditions. No
      propellane-type product was obtained in the solvolyses of 1
      bromobicyclo[3.3.1]nonane, 2-methylidenebicyclo[3.3.1]non-1-yl
      heptafluorobutyrate, and 3, 3-dimethyl-2-thioxobicyclo[3.3.1]non-1-yl tosylate.
      The factors that permit the formation of the propellane-type product from the
      intermediate bridgehead cations are examined with the aid of theoretical
      calculations at PM3 and B3LYP/6-31G.

PMID- 10956481
TI  - Neighboring group participation of the indole nucleus: An unusual DAST-mediated
      rearrangement reaction
AB  - A rearrangement reaction involving the indole nucleus was investigated using
      stereochemical markers and low-temperature NMR experiments. Treatment of (3S, 4S)
      3-hydroxy-4-(2-phenyl-1H-indol-3-yl)-piperidine-1-carboxylic acid benzyl ester
      (>90% ee) with diethylaminosulfur trifluoride gave stereospecifically (3S, 4S)-4
      fluoro-3-(2-phenyl-1H-indol-3-yl)-piperidine-1-carboxylic acid benzyl ester (>90%
      ee) with complete regioselectivity. The initial formation of a reactive
      spirocyclopropyl-3H-indole intermediate is believed to be responsible for the
      stereo- and regiochemical outcome of the reaction.

PMID- 10956480
TI  - The synthesis and evaluation of a solution phase indexed combinatorial library of
      non-natural polyenes for reversal of P-glycoprotein mediated multidrug
      resistance.
AB  - A combinatorial library of polyenes, based on (-)-stipiamide, has been
      constructed and evaluated for the discovery of new multidrug resistance reversal
      agents. A palladium coupling was used to react each individual vinyl iodide with
      a mixture of the seven acetylenes at near 1:1 stoichiometry. The coupling was
      also used to react each individual acetylene with the mixture of six vinyl
      iodides to create 13 pools indexed in two dimensions for a total of 42 compounds.
      Individual compounds were detected at equimolar concentration. The vinyl iodides,
      made initially using a crotylborane addition to generate the anti1,2
      hydroxylmethyl products, were now made using a more efficient norephedrine
      propionate boron enolate aldol reaction. The indexed approach, ideally suited for
      cellular assays that involve membrane-bound targets, allowed for the rapid
      identification of reversal agents using assays with drug-resistant human breast
      cancer MCF7-adrR cells. Intersections of potent pools identified new compounds
      with promising activity. Aryl dimension pools showed R = ph and naphthyl as the
      most potent. The acetylene dimension had R' = phenylalaninol and alaninol as the
      most potent. Isolated individual compounds, both active and nonpotent, were
      assayed to confirm the library results. The most potent new compound was 4ek (R =
      naphthyl, R' = phenylaninol) at 1.45 microM. Other nonnatural individual naphthyl
      amide compounds showed potent MDR reversal including the morpholino-amide 4ej
      (1.69 microM). Synergistic activities attributed to the two ends of the molecule
      were also identified. Direct interaction with Pgp was established by ATPase and
      photoaffinity displacement assays. The results indicate that both ends of the
      polyene reversal agent are involved in Pgp interaction and can be further
      modified for increased potency.

PMID- 10956482
TI  - Electrochemical studies of seven regioisomers of Tris
AB  - Seven of the possible 46 constitutional isomers of
      tris[di(ethoxycarbonyl)methano[60]fullerene have been isolated and their
      electrochemical properties studied in CH(2)Cl(2). A two-electron controlled
      potential electrolysis of each of these isomers results in competing retro-Bingel
      and isomerization reactions with preferential loss of one or two of the addends.
      PM3 and AM1 computational studies indicate that while the reactivity of neutral
      precursors is kinetically controlled, charging of the neutral species with two
      electrons results in an umpolung of reactivity and introduction of thermodynamic
      control. Lowering the electrolysis temperature increases the proportion of
      isomerization, and a new tris-isomer never obtained before via synthetic methods
      has been isolated.

PMID- 10956483
TI  - Epoxidation of trans-cyclooctene by Methyltrioxorhenium/H(2)O(2): reaction of
      trans-epoxide with the monoperoxo complex
AB  - The epoxidation of trans-cyclooctene (trans-1) with the MTO/H(2)O(2), MTO/UHP,
      and NaY/MTO/H(2)O(2) oxidants leads to a mixture of trans/cis-olefins 1,
      trans/cis-epoxides 2, and the cis-diol 3. While the oxygen transfer proceeds
      stereoselectively, the monoperoxo rhenium complex A, which is generated in situ
      during the catalytic cycle, is responsible for the facile deoxygenation,
      isomerization, and hydrolysis of the trans-epoxide. In the case of the
      homogeneous MTO/H(2)O(2) system, rapid decomposition of the catalytically active
      rhenium species into HReO(4) circumvents the formation of such side products. In
      contrast, for the heterogeneous oxidants MTO/UHP and NaY/MTO/H(2)O(2), the
      catalytically active rhenium species are sufficiently stabilized and survive long
      enough to promote the observed side reactions.

PMID- 10956484
TI  - Asymmetric cyclopropanation of allylic alcohols employing Sulfonamide/Schiff base
      ligands

PMID- 10956485
TI  - Synthesis of 2-CF(3)-tetrahydroquinoline and quinoline derivatives from CF(3)-N
      aryl-aldimine.

PMID- 10956486
TI  - Absence of detectable freely diffusing radicals during the formation of an
      aromatic grignard reagent

PMID- 10956487
TI  - Development of an efficient intermediate, alpha-[2-(trimethylsilyl)ethoxy]-2-N-
      [2-(trimethylsilyl)ethoxycarbonyl]folic acid, for the synthesis of folate (gamma)
      conjugates, and its application to the synthesis of folate-nucleoside conjugates.

PMID- 10956488
TI  - Imidoylation of acidic hydrocarbons with selenium and isocyanides: A new
      synthetic method for preparation of selenoimidates

PMID- 10956489
TI  - Complexation of a peptidocalix[4]arene, a vancomycin mimic, with alanine
      containing guests by NMR diffusion measurements.

PMID- 10956490
TI  - Solution structure of a chiral dialkylboron enolate by NMR spectroscopy and
      simulated annealing: unusual stabilization of this intermediate by a boron
      nitrogen interaction

PMID- 10956491
TI  - Facile approach to 4-substituted 2(5H)-furanones

PMID- 10956492
TI  - Efficient procedure for the reduction of alpha-amino acids to enantiomerically
      pure alpha-methylamines.

PMID- 10956493
TI  - Free-radical reaction of imine derivatives in water

PMID- 10956495
TI  - Chlorofluoroethenes. Thermochemical stability and cis-effect

PMID- 10956494
TI  - A versatile polymer-supported 4-(4-Methylphenyl(chloro)methyl)phenoxy linker for
      solid-phase synthesis of pseudopeptides

PMID- 10956496
TI  - Convenient synthesis of the water-soluble ligand hexasodium Tris(4
      phosphonatophenyl)phosphine

PMID- 10956497
TI  - Synthesis of 7,10-Bis(2-halophenyl)tribenzo

PMID- 10956498
TI  - TiCl(4)-n-Bu(4)NI as a reducing reagent: pinacol coupling and enolate formation
      from alpha-haloketones

PMID- 10956499
TI  - A new case of chiral recognition between isotopomers. Preparation and study of
      (R) and (S) perdeuterio 2,2, 2-trifluoro-1-(1-pyrenyl)ethanol

PMID- 10956500
TI  - Enantioselective synthesis of (+)-juvabione.

PMID- 10956501
TI  - Competition between hetero-diels-alder and chelotropic addition of sulfur
      dioxide. Theoretical and experimental substituent effects on the relative
      stability of 3,6-dihydro-1,2-oxathiin-2-oxides (Sultines) and 2,5
      dihydrothiophene-1,1-dioxides (Sulfolenes). Anomeric effects in sultine and 6
      substituted derivatives

PMID- 10956502
TI  - Synthesis of optically active 5-substituted-2-pyrrolidinone derivatives having
      atropisomeric structure and 3,5-cis-selective reaction of their enolates with
      electrophiles

PMID- 10956503
TI  - A versatile polymer-supported 4-(4-Methylphenyl(chloro)methyl)phenoxy linker for
      solid-phase synthesis of pseudopeptides

PMID- 10956504
TI  - Nonracemic 2-diazo-1-oxiranyl-ethanone, a versatile chiral epoxide educt in
      diazocarbonyl reactions
AB  - (S)-(-)-2-Diazo-1-oxiranyl-ethanone, prepared in two steps from (R)-(+)-glycidol,
      has been employed as an intermediate in several characteristic diazocarbonyl
      reactions to yield novel, nonracemic products including an epoxy quinoxaline and
      epoxy thiazoles and oxazoles.

PMID- 10956505
TI  - Titanium(IV) chloride and the amine-promoted baylis-hillman reaction
AB  - In the Baylis-Hillman reaction, we found that, when the reactions of
      arylaldehydes with methyl vinyl ketone were carried out at <-20 degrees C using a
      catalytic amount of amine as a Lewis base in the presence of titanium(IV)
      chloride, the chlorinated compounds 1 could be obtained as the major product in
      very high yields for various arylaldehydes. In addition, acrylonitrile could
      undergo the same reaction to give the corresponding chlorinated product in
      moderate yield.

PMID- 10956506
TI  - Novel natural products from soil DNA libraries in a streptomycete host.
AB  - As a route to accessing the potential chemical diversity of uncultivable microbes
      from the soil, combinatorial biosynthetic libraries were constructed by cloning
      large fragments of DNA isolated from soil into a Streptomyces lividans host. Four
      novel compounds, terragines A (1), B (2), C (3), and D (4), were isolated from
      recombinant 436-s4-5b1, and another novel compound, terragine E (5), was isolated
      from 446-s3-102g1. The structures were determined by a combination of
      spectroscopic techniques, primarily 2D NMR.

PMID- 10956507
TI  - Asymmetric synthesis of (-)-tetrahydrolipstatin: an anti-aldol-based strategy.
AB  - A stereoselective synthesis of (-)-tetrahydrolipstatin is described. The
      synthesis involves an asymmetric ester derived titanium enolate anti-aldol
      reaction, a nitro-aldol reaction to append the C-2' C(11) side chain, and a
      diastereoselective reduction of a beta-hydroxy ketone to an anti-1,3-diol
      functionality followed by its elaboration to (-)-tetrahydrolipstatin.

PMID- 10956508
TI  - Deprotonation of benzylic ethers using a hindered phosphazene base. A synthesis
      of benzofurans from ortho-substituted benzaldehydes.
AB  - The hindered nonionic phosphazene base P(4)-t-Bu efficiently deprotonates o
      arylmethoxy benzaldehydes, leading to a direct synthesis of benzofurans. Strong
      ionic bases such as LDA, LiTMP, and KH failed.

PMID- 10956509
TI  - Dynamic hemicarcerands and hemicarceplexes.
AB  - The reversible nature of the imine bond formation in CDCl(3) solution has been
      exploited to exchange substituted for unsubstituted m-phenylenediamine (MPD)
      units in hemicarcerand octaimines. Moreover, acid-catalyzed imine exchange has
      been shown to provide a novel mechanism whereby ferrocene (Fc) can be released as
      an entrapped guest from the hemicarceplex C(2)B(4)&crcldt;Fc dissolved in CDCl(3)
      to give the hemicarcerand C(2)B(4) when excess of both MPD and trifluoroacetic
      acid are present.

PMID- 10956510
TI  - Asymmetric synthesis of a (2Z,7E)-cyclononadiene by an intramolecular
      cycloalkylation and insight to its conformational properties
AB  - Here, we report a novel synthesis of a monosubstituted, enantio- and
      diastereomerically enriched trans-cyclononadienol. The reaction consists of an
      enantioselective (-)-sparteine-mediated allylic lithiation of an achiral 7
      chlorononadienyl carbamate and a subsequent stereospecific intramolecular
      allyllithium-allyl chloride coupling. The stereochemical course of the
      cyclization has been determined, and the high configurative stability of the
      chiral nine-membered carbocycle has been investigated by kinetic measurements and
      rationalized by computational calculations.

PMID- 10956511
TI  - A straightforward modular approach to NLO-active beta-amino vinyl nitrothiophenes
AB  - Secondary amines add very efficiently to 2-ethynyl-5-nitrothiophene to give beta
      amino vinyl nitrothiophenes, a novel class of push-pull chromophores. According
      to first HRS measurements these highly solvochromic compounds with relatively
      short dipole axes display remarkably high static first hyperpolarizabilities = 29
      31 x 10(-)(30) esu.

PMID- 10956512
TI  - Syntheses of optically active trifluoronorcoronamic acids.
AB  - Syntheses of optically active trifluoronorcoronamic acid 6 and its diastereomer 9
      are described. Highly stereospecific and diastereoselective S(N)2 cyclization of
      gamma-cyanohydrins 3a and 3b gave cyclopropyl nitriles 4a and 4b. Hydrolysis of
      the cyano group and deprotection of the amino group of 4a provide
      trifluoronorcoronamic acid 6. Hofmann rearrangement of the amide which was
      generated by hydrolysis of the cyano group and oxidative cleavage of the aryl
      ring of 4b to provide trifluoro-allo-norcoronamic acid 9.

PMID- 10956513
TI  - Palladium(II)-catalyzed cyclization of urethanes and total synthesis of 1
      deoxymannojirimycin.
AB  - The palladium(II)-catalyzed cyclization of the urethane 8, which was derived from
      D-mannitol, gave the cyclic compound 9 with excellent diastereoselectivity.
      During these transformations, the Pd(II) species are not reduced and thus the
      catalyst can recycle without its reoxidation. The cycloadduct 9 was converted to
      1-deoxymannojirimycin.

PMID- 10956514
TI  - Determination of absolute configurations of amines and amino acids using
      nonchiral derivatizing agents (NCDA) and deuterium NMR.
AB  - Enantiomeric analysis and empirical determination of the absolute configuration
      of amines and amino acids can be easily performed using acetyl-d(3) chloride as a
      nonchiral derivatizing agent (deuterium probe) and deuterium NMR in a chiral
      solvent (Courtieu's method). In the case of amino acids, derivatization to amido
      esters, performed with methanol-d(4) and acetyl-d(3) chloride, gives a double
      opportunity for enantiomeric analysis.

PMID- 10956515
TI  - Self-assembly of oligomeric porphyrin rings.
AB  - A cobalt porphyrin equipped with two different but geometrically complementary
      pyridine ligands self-assembles to form an unusually stable complex with
      approximately 12 porphyrin monomers arranged in a macrocyclic array.

PMID- 10956516
TI  - Facile, fmoc-compatible solid-phase synthesis of peptide C-terminal thioesters.
AB  - A short route to peptide C-terminal thioesters was developed that does not
      require the use of special linkers or resins and is compatible with standard Fmoc
      chemistry. Following conventional solid-phase peptide synthesis, an excess of
      Me(2)AlCl and EtSH in dichloromethane cleaves peptides from Wang or Pam resins to
      give the corresponding thioesters directly in good yield and purity.

PMID- 10956517
TI  - HMPA promotes retro-aldol reaction, resulting in syn-selective addition of
      lithiated 1-naphthylacetonitrile to aromatic aldehydes
AB  - In HMPA-THF solution, lithiated 1-naphthylacetonitrile undergoes highly syn
      selective addition to aromatic aldehydes, providing the first access to such syn
      aldols. Syn-selectivity is also observed with two other arylacetonitriles.
      Aldolate equilibration and crossover experiments demonstrate that HMPA promotes
      retro-aldol reaction and that aldol diastereoselectivity under these conditions
      is thermodynamically controlled.

PMID- 10956518
TI  - Asymmetric cyclopentannelation. Chiral auxiliary on the allene.
AB  - An enantioselective variant of the synthesis of cross-conjugated cyclopentenones,
      based on D-glucose-derived chiral auxiliaries, is described. Minor modification
      of the method makes it applicable to the preparation of both enantiomeric series
      of products. Both enantiomers of the key intermediate in our roseophilin
      synthesis have been prepared.

PMID- 10956519
TI  - Singlet-triplet energy gaps in highly stabilized nitrenium ions: experimental and
      theoretical study of 1,3-dimethylbenzotriazolium Ion
AB  - The first experimental determination of a singlet-triplet energy gap (DeltaE(st))
      for an organic nitrenium ion was made for 1, 3-dimethylbenzotriazolium ion 1.
      Laser flash photolysis was used to determine DeltaE(st) for this persistent
      nitrenium ion and a value of -66 +/- 3 kcal mol(-)(1) was obtained. DFT
      calculations show excellent agreement with the experiment.

PMID- 10956520
TI  - Photooxidation of arylmethyl bromides with mesoporous silica FSM-16
AB  - A mesoporous silica FSM-16 was found to be a recyclable oxidizing promoter of
      arylmethyl bromides for the preparation the corresponding carboxylic acids,
      aldehydes, or ketones under photoirradiation conditions.

PMID- 10956521
TI  - Asymmetric synthesis of actinoidic acid derivatives.
AB  - Synthesis of fully protected actinoidic acid derivative 3 and selectively
      protected biaryl bisamino acid 4, intermediates for vancomycin total synthesis,
      are reported.

PMID- 10956522
TI  - Concise synthesis of (S,S)-(+)-dehydrohomoancepsenolide.
AB  - A concise total synthesis of the bis-butenolide 3 in optically active form is
      reported. Key steps are a zinc-mediated "three-component coupling" with formation
      of dienyne 9 which undergoes ring closing metathesis (RCM) on treatment with
      (PCy(3))(2)Cl(2)Ru=CHPh. Dimerization of the resulting butenolide 11 is then
      achieved via alkyne metathesis using (tBuO)(3)W&tbd1;CCMe(3) as the catalyst. A
      Lindlar reduction completes this synthesis which delivers product 3 in only five
      steps with an overall yield of 25%.

PMID- 10956523
TI  - Total synthesis of cristatic acid.
AB  - The first total synthesis of cristatic acid 1, an antibiotic endowed with
      considerable activity against Gram-positive bacteria, hemolytic properties, and
      significant cytotoxicity, is described. Key to success are the formation of its
      2,4-disubstituted furan moiety via a palladium-catalyzed alkylation of
      vinylepoxide 10 derived from sulfonium salt 8 and the use of SEM ethers as the
      protecting groups for the phenolic OH functions.

PMID- 10956524
TI  - The first electrochemically active cuppedophanes:
      bis(tetrathiafulvalene)cuppedophanes
AB  - The synthesis of the first tetrathiafulvalene-containing cuppedophanes is
      reported, together with conformational study of the structures by (1)H NMR
      spectroscopy. The bis(TTF)cuppedophane 6 represents a novel type of cuppedophane.

PMID- 10956525
TI  - Stereoselective approach to hydroxyindolizidines: protection/deprotection of the
      nitrone functionality via cycloaddition/retrocycloaddition.
AB  - The enantiomerically pure indolizidine (-)-21 has been synthesized starting from
      L-malic acid. The key intermediate 20 has been assembled through an
      intramolecular 1,3-dipolar cycloaddition of a nitrone generated in situ by
      retrocycloaddition from isoxazolidine 17 or 18. The configuration of the new
      three stereocenters was set up with complete control in the cycloaddition step.
      The presented synthetic route provides a general and highly selective methodology
      toward indolizidines having the [1,8a]-cis configuration.

PMID- 10956526
TI  - The formal total synthesis of (+/-)-strychnine via a cobalt-mediated [2 + 2 +
      2]cycloaddition.
AB  - A short, highly convergent total synthesis of racemic isostrychnine, and thus
      strychnine, has been completed. The route involves 14 steps in the longest linear
      sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an
      alkynylindole nucleus to acetylene.

PMID- 10956527
TI  - A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide and approaches
      to the syntheses of (+/-)-6-epi-, (+/-)-15-epi-, and (+/-)-6,15
      bisepidysidiolide.
AB  - A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide (1), a
      structurally novel sponge metabolite that inhibits the cdc25A protein
      phosphatase, and approaches to the syntheses of (+/-)-15-epi- (34), (+/-)-6-epi-
      (36), and (+/-)-6, 15-bisepidysidiolide (39) are described.

PMID- 10956529
TI  - Convergence of mechanistic pathways in the Palladium(0)-catalyzed cross-coupling
      of alkenylsilacyclobutanes and alkenylsilanols
AB  - Alkenylsilacyclobutanes and alkenylsilanols react in palladium-catalyzed cross
      coupling reactions via the same intermediate, produced in situ upon treatment of
      either starting material with tetrabutylammonium fluoride.

PMID- 10956528
TI  - Practical ruthenium/lipase-catalyzed asymmetric transformations of ketones and
      enol acetates to chiral acetates.
AB  - Ketones were asymmetrically transformed to chiral acetates by one-pot processes
      using a lipase and an achiral ruthenium complex under 1 atm of hydrogen gas in
      ethyl acetate. Molecular hydrogen was also effective for the transformation of
      enol acetates to chiral acetates without additional acyl donors with the same
      catalyst system.

PMID- 10956530
TI  - Reverse of regioselectivity in intramolecular nucleophilic substitution of pi
      allyl palladium species. Highly selective formation of vinylic cyclopropanes via
      the Pd(0)-catalyzed coupling-cyclization reaction of organic iodides with 2-(2',
      3'-Dienyl)malonates
AB  - Vinylic cyclopropanes were formed highly selectively via the Pd(PPh(3))(4)
      catalyzed insertion-intramolecular nucleophilic substitution reaction of aryl or
      1-alkenyl iodides with 2-(2', 3'-dienyl)malonates. The regioselectivity observed
      here is different from what was reported by Cazes et al.

PMID- 10956531
TI  - 1,3-dipolar cycloadditions as a tool for the preparation of multivalent
      structures.
AB  - The construction of multivalent structures such as sugar heterodimers,
      glycoclusters, calix sugars, multicalixarenes, and glycocyclodextrins is designed
      by using 1,3-dipolar cycloaddition as a versatile and efficient tool which allows
      the creation of heterocyclic bridges between the different units that are
      coupled.

PMID- 10956532
TI  - A simple and stereospecfic route to 2,6-disubstituted 4-hydroxypiperidines.
      Synthesis of dendrobate alkaloid (+)-241D and formal synthesis of (-)
      indolizidine 167B.
AB  - The condensation of enantiopure beta-amino esters with beta-ketoesters followed
      by cyclization and decarboxylation afforded 2,3-dihydro-4-pyridones 3, which were
      selectively hydrogenated to provide 2,6-disubstituted 4-hydroxypiperdines.

PMID- 10956534
TI  - Kinetic investigations of product inhibition in the amino alcohol-catalyzed
      asymmetric alkylation of benzaldehyde with diethylzinc
AB  - In situ reaction rate measurements help to define the role of product inhibition
      in the asymmetric alkylation of benzaldehyde with diethylzinc using (-)-MIB as a
      chiral reagent. Reaction calorimetry and kinetic modeling demonstrated that the
      rate behavior over consecutive reactions may only be rationalized when reversible
      binding of the product alkoxide is taken into consideration. These results may
      have implications for the conversion dependence of product enantioselctivity in
      reactions using enantioimpure catalysts.

PMID- 10956533
TI  - Studies toward the tricyclic core of phomactin A. Synthesis of the reduced
      furanochroman subunit.
AB  - An approach to the tricyclic core of phomactin A is described via the synthesis
      of a reduced furanochroman model. Key elements of this study include the use of a
      highly functionalized 1-oxadecalone derivative as a template for the
      stereoselective introduction of functionality and a tandem retro aldol-epoxide
      opening-cyclization sequence for elaboration of the dihydrofuran ring.

PMID- 10956535
TI  - Synthesis of enantiopure alpha,alpha-disubstituted amino acids from the
      asymmetric Strecker reaction products of aldehydes.
AB  - Treatment of the enolates of 4 generated from the asymmetric Strecker reaction
      products with alkyl halides or aldehydes provided the corresponding
      functionalized products with high diastereoselectivity. Deprotection of these
      products afforded the corresponding enantiopure alpha,alpha-dialkyl amino acids.

PMID- 10956536
TI  - An alpha,alpha'-dioxothione and its
AB  - In the reaction of Ninhydrin (1a)/1,2,3-indantrione (1b) with potassium
      thiotosylate, 1,4-oxathiin 6 is formed in up to 63% yield as the trapping product
      of the intermediary alpha,alpha'-dioxothione 1c with trans-cyclooctene (3a).
      Additionally, up to 18% of the available sulfur is transferred to olefin 3a to
      thiirane 3b through the intermediary oxathiirane.

PMID- 10956537
TI  - On the regioselectivity of the Ru-catalyzed intramolecular [5 + 2] cycloaddition.
AB  - The influence of substituents on which cyclopropyl bond cleaves in the
      cycloisomerization of cyclopropylenynes catalyzed by
      CpRu(N&tbd1;CCH(3))(3)(+)PF(6)(-) is compared to the corresponding Rh-catalyzed
      reaction. With the trans cyclopropyl substrates, the bond energy of the cleaving
      bond appears to be an important factor. With cis cyclopropyl substrates, steric
      effects appear to dominate.

PMID- 10956538
TI  - Stereoselective diels-alder reactions of chiral anthracenes
AB  - Various chiral (9-anthryl)carbinol templates undergo Diels-Alder cycloadditions
      with a variety of symmetric and nonsymmetric dienophiles with excellent pi-facial
      selectivity and regioselectivity, under both thermal and Lewis acid catalyzed
      conditions.

PMID- 10956539
TI  - Atom transfer reactions of TMM diyls directed toward the synthesis of rudmollin.
AB  - Intramolecular hydrogen atom transfer to a trimethylenemethane (TMM) diradical
      has been explored as a route to the antileukemial agent, rudmollin (1).

PMID- 10956540
TI  - Aryl radical cyclizations: one-Pot syntheses of protoberberine and pavine
      alkaloids.
AB  - Treatment of 2-(2'-bromo-beta-phenethyl)isocarbostyrils 7 with AIBN-Bu(3)SnH in
      boiling benzene gave 8-oxoberbines 3 in good yields. A similar treatment of 2-(2'
      bromo-beta-phenethyl)isoquinolinium bromides 6 and their nor- and homoanalogues
      (10,11) induced 6-, 5-, and 7-exo radical closures in a one-pot manner to give
      protoberberines 2, dibenzo[b,g]indolizidine 14a and, dibenzo[a, h]-1
      azabicyclo[5.4.0]undecane 15a, respectively. A one-pot radical cyclization of 1
      (2'-bromobenzyl)isoquinoline methiodide 18a gave a pavine alkaloid, (+/-)
      algemonine (19a).

PMID- 10956541
TI  - A novel and effective procedure for the preparation of glucuronides.
AB  - 6-Phenylthio-6-deoxy-D-glucopyranosides were easily prepared from 6-hydroxy-D
      glucopyranosides and employed as effective glycosyl donors or acceptors. And the
      resulting coupling products were then readily converted into the corresponding D
      glucuronide-containing compounds.

PMID- 10956542
TI  - A short catalytic enantioselective synthesis of the proinflammatory eicosanoid
      12(R)-hydroxy- 5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid (12(R)-HETE).
AB  - A new and effective pathway is described for the synthesis of 12(R)-HETE and the
      12(S)-enantiomer from the common intermediates 4 and 8.

PMID- 10956544
TI  - Rhodium-catalyzed reformatsky-type reaction
AB  - A novel Reformatsky-type reaction was developed using RhCl(PPh(3))(3) and
      diethylzinc. Inter- and intramolecular Reformatsky-type reactions were achieved
      efficiently under mild reaction conditions to give beta-hydroxy esters.

PMID- 10956543
TI  - Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B.
AB  - An efficient new process is described for the synthesis of ecteinascidin ET-743
      (1) and phthalascidin (2), starting from readily available cyanosafracin B (3).

PMID- 10956546
TI  - Linear free energy relationships implicate three modes of binding for
      fluoroaromatic inhibitors to a mutant of carbonic anhydrase II

PMID- 10956547
TI  - Stereoselectivity of macrocyclic ring-closing olefin metathesis

PMID- 10956548
TI  - NF-IL6 and CRE elements principally account for both basal and interleukin-1 beta
      induced transcriptional activity of the proximal 528bp of the PGHS-2 promoter in
      amnion-derived AV3 cells: evidence for involvement of C/EBP beta.
AB  - Prostaglandin H synthase (PGHS)-2 promoter fragments (-528 to +9 bp and 5'
      unidirectional deletions thereof) were cloned upstream of the chloramphenicol
      acetyl-transferase (CAT) reporter gene. These were transfected into amnion
      derived AV3 cells. The region, -528 to -203, which includes NF-kappa B sites, had
      little influence on CAT expression. The region, -203 and -52, however, was
      responsible for most of the basal promoter activity and also conferred
      responsiveness to interleukin (IL)-1 beta (>3-times basal). Point mutations of NF
      IL6 and cAMP response element (CRE) in this region reduced both basal and IL-1
      beta-stimulated production of CAT; dual mutation eliminated IL-1 beta
      responsiveness. Factors in nuclear extracts from control or IL-1 beta-stimulated
      AV3 cells specifically complexed the NF-IL6 and CRE sequences. However, the NF
      IL6 and CRE oligonucleotides cross-competed, suggesting a common factor. C/EBP
      beta was identified by supershift assay as interacting with both sequences. To a
      lesser extent C/EBP alpha and delta also interacted with the NF-IL6 site.
      However, CRE binding protein (CREB), was absent from the complex with the CRE. In
      conclusion, NF-IL6 and CRE elements principally account in AV3 amnion cells for
      basal and IL-1 beta-inducible transcriptional activity of the proximal 528 bp of
      the PGHS-2 promoter, while NF-kappa B elements play no substantial role. C/EBPs,
      particularly C/EBPbeta, are implicated in control of PGHS-2 transcription through
      the NF-IL6 and CRE sites.

PMID- 10956549
TI  - Developmental expression of Y-box protein 1 mRNA and alternatively spliced Y-box
      protein 3 mRNAs in spermatogenic cells in mice.
AB  - Y-box proteins bind DNA and RNA and are characterized by a cold shock domain and
      a carboxyl-terminus containing clusters of aromatic and basic residues that
      alternate with clusters of acidic residues. Y-box proteins 1 and 3 in mouse
      testis were cloned here by 3' rapid amplification of cDNA ends (RACE) using a
      degenerate primer. Northern blots and reverse transcription-polymerase chain
      reaction (RT-PCR) established that the levels of Y-box protein 1 and 3 mRNAs are
      regulated individually: (i) Y-box protein 1 mRNA is strongly expressed in kidney,
      whereas Y-box protein 3 mRNA is strongly expressed in heart and muscle; (ii) Y
      box protein 1 and 3 mRNAs are weakly expressed in early prepubertal testis and
      strongly expressed in pachytene spermatocytes, round spermatids, and elongated
      spermatids; and (iii) prepubertal testes and meiotic and haploid spermatogenic
      cells express two alternatively spliced Y-box protein 3 mRNAs encoding isoforms
      with different carboxyl termini, whereas somatic tissues primarily express one
      form. Sucrose gradients reveal that approximately 27% of both Y-box protein 3
      mRNAs are translationally active in adult testis. In conclusion, spermatogenic
      cells in mice express five isoforms of Y-box proteins including Y-box protein 1,
      and two isoforms each of Y-box proteins 2 and 3. This multiplicity is intriguing
      because Y-box proteins are thought to activate transcription and repress
      translation in spermatogenic cells.

PMID- 10956545
TI  - Enhancing the enantioselectivity of lipase in transesterification by substrate
      matching: an enzyme memory based approach.
AB  - The substrate matching strategy is described as a new approach for effectively
      enhancing the lipase enantioselectivity in organic solvent. In the lipase
      catalyzed transesterifications of 3a-c, higher enantioselectivities have been
      achieved using 1a-c, respectively, as the structurally matched acyl donors.

PMID- 10956550
TI  - The human Y chromosome genes BPY2, CDY1 and DAZ are not essential for sustained
      fertility.
AB  - Deletions of the AZFc interval of the human Y chromosome are found in >5% of male
      patients with idiopathic infertility and are associated with a severely reduced
      sperm count. The most common deletion type is large (>1 Mb) and removes members
      of the Y-borne testis-specific gene families of BPY2, CDY1, DAZ, PRY, RBMY2 and
      TTY2, which are candidate AZF genes. Four exceptional individuals who have
      transmitted a large AZFc deletion naturally to their infertile sons have,
      however, been described. In three cases, transmission was to an only son, but in
      the fourth case a Y chromosome, shown to be deleted for all copies of DAZ, was
      transmitted from a father to his four infertile sons. Here we present a second
      family of this latter type and demonstrate that an AZFc-deleted Y chromosome
      lacking not only DAZ, but also BPY2 and CDY1, has been transmitted from a father
      to his three infertile sons. Polymerase chain reaction (PCR) and Southern blot
      analyses revealed no difference in the size of the AZFc deletion in the father
      and his sons. We propose that the father carries rare alleles of autosomal or X
      linked loci which suppress the infertility that is frequently associated with the
      absence of AZFc.

PMID- 10956551
TI  - AZFa deletions in Sertoli cell-only syndrome: a retrospective study.
AB  - Lack of data on the genotype-phenotype relationship in cases of AZF
      microdeletions is due to the limited number of histological investigations in
      human male infertility cases. We investigated the possibility of retrospective
      detection of Yq11 microdeletions by using DNA extracted from diagnostic
      testicular biopsies. We used histological criteria to select two series of
      material: 22 biopsies with Sertoli cell-only syndrome and 14 biopsies with
      maturation arrest at the spermatocyte I stage. Two markers, DFFRY and DAZ, were
      tested by nested polymerase chain reaction (PCR) in the two series. In the
      Sertoli cell-only syndrome series, we found four deletions affecting the DFFRY
      gene (18.2%). In the second series, no deletions were detected. Two conclusions
      may be considered, although the number of specimens analysed is limited: (i) the
      frequency of deletions observed in Sertoli cell-only syndrome allows us to
      suggest that deletion in the AZFa region may be involved in this pathology; and
      (ii) retrospective studies may yield some additional elements in our search for
      eventual genotype-phenotype relationships.

PMID- 10956552
TI  - Detection of human novel developmental genes in cDNA derived from replicate
      individual preimplantation embryos.
AB  - We have constructed amplified cDNA preparations from replicate samples of human
      oocytes and individual preimplantation embryos. Differential display of the cDNA
      preparations shows disparate patterns of gene expression in the individual
      embryos at all stages of preimplantation development. The variation in patterns
      of genes expressed is in part due to the low starting cell number undergoing the
      reverse transcription-polymerase chain reaction (RT-PCR) step in the preparation
      of the amplified cDNAs. Despite this variability, the use of replicate embryo
      samples makes it possible to identify and isolate human genes specifically
      expressed at the different stages of human preimplantation development from the
      unfertilized oocyte to the blastocyst stage.

PMID- 10956553
TI  - Adrenomedullin is an autocrine regulator of endothelial growth in human
      endometrium.
AB  - Human endometrium is a mucosa served by a microvascular blood supply that
      involves benign angiogenesis under the control of ovarian steroids throughout
      reproductive life. Adrenomedullin is a multifunctional 52-amino acid peptide
      involved in numerous physiological and pathological processes, including
      angiogenesis, growth regulation, differentiation, vasodilation and smooth muscle
      relaxation. We have previously shown that adrenomedullin is present in the human
      uterus. To investigate further the role of adrenomedullin in human endometrial
      angiogenesis, a method for the isolation and culture of non-pregnant endometrial
      endothelium was developed. Enzymatic dispersion and 'Percoll' gradient
      centrifugation, followed by positive selection using Ulex europaeus agglutinin
      coated immunomagnetic beads, yielded pure isolates of endothelium. The cells
      formed a typical 'cobblestone' monolayer within 5-7 days and expressed the
      classic endothelial markers, CD31 and von Willebrand factor. The presence of
      adrenomedullin immunoreactivity in endometrial endothelial cells was shown by
      immunohistochemistry both in vitro and in vivo. Adrenomedullin promotes growth of
      endothelial cells as measured by [methyl-(3)H] thymidine uptake. Adrenomedullin
      also induced cyclic AMP in endometrial endothelial cells. These results
      demonstrate, for the first time, that adrenomedullin is an autocrine growth
      factor for human endometrial endothelial cells and is thus involved in
      endometrial angiogenesis.

PMID- 10956554
TI  - Genetic abnormalities detected by comparative genomic hybridization in a human
      endometriosis-derived cell line.
AB  - Comparative genomic hybridization (CGH) was used in parallel with fluorescence in
      situ hybridization (FISH) and conventional karyotyping to perform a genome-wide
      survey of DNA gains and losses in the endometriosis-derived permanent cell line,
      FbEM-1. The cytogenetic analysis showed a complex karyotype with numerical
      changes and multiple chromosome aberrations, including the der(1) complement
      marker exhibiting a large homogenous staining region (HSR). The chromosomal
      rearrangement interpreted as der(5) t(5;6)(q34;p11) was found in the majority of
      the metaphases indicating a clonal abnormality. Repeated CGH experiments
      demonstrated over-representation of chromosomes 1, 2, 3, 5, 6p, 7, 16, 17q, 20,
      21q and 22q, while chromosomes 6q, 9, 11p, 12, 13q, 18 and X were under
      represented. Using DNA from the original endometriotic tissues, including a
      peritoneal implant and ovarian endometrioma, CGH analysis revealed loss of DNA
      copy number on 1p, 22q and chromosome X, while gain was found on chromosomal arms
      6p and 17q. FISH analysis confirmed that the gain at 17q includes amplification
      of the proto-oncogene HER-2/neu in 16% of the FbEM-1 nuclei and in 12% of cells
      from the primary ovarian endometrioma tissue. These findings demonstrate that
      FbEM-1 cells share certain molecular cytogenetic features with the original
      tissue and suggest that chromosomal instability is important in the development
      of endometriosis.

PMID- 10956555
TI  - Increased concentrations of secretory leukocyte protease inhibitor in peritoneal
      fluid of women with endometriosis.
AB  - Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human
      leukocyte elastase. We investigated whether SLPI was present in the peritoneal
      fluid of women with endometriosis and to clarify the role of SLPI in the
      pathogenesis of endometriosis. Western blot analyses revealed that SLPI protein
      was detected as a 12 kDa band in peritoneal fluid. The peritoneal fluid
      concentrations of SLPI, elastase and interleukin-6 were assayed by enzyme-linked
      immunosorbent assays (ELISA). SLPI concentrations and the SLPI/elastase ratio in
      the peritoneal fluid of women with endometriosis were higher than in samples from
      women without endometriosis. There was no significant correlation between
      concentrations of SLPI and interleukin-6 in the peritoneal fluid.
      Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive
      staining in peritoneal macrophages, but not lymphocytes. The present findings
      suggest that SLPI found in the peritoneal fluid of patients with endometriosis
      may contribute to the pathogenesis of endometriosis.

PMID- 10956556
TI  - Changes in beta(2)-adrenoceptor expression and in adenylyl cyclase and
      phosphodiesterase activity in human uterine leiomyomas.
AB  - Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in
      adult women. In the present study we have investigated the expression level of
      alpha(2)- and beta(2)-adrenoceptors, and the adenylyl cyclase and
      phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium.
      Our results show that the alpha(2)/beta(2)-adrenoceptor ratio is increased in
      leiomyoma, due to a significant decrease in beta(2)-adrenoceptor expression.
      These changes were not due to an increased innervation, as the tumour tissue was
      completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of
      leiomyoma membranes was found to be approximately 50% lower, whereas the
      phosphodiesterase activity was significantly increased (by approximately 100%).
      We found that stimulating an increase in intracellular cyclic AMP, by adenylyl
      cyclase activity through beta(2)-adrenoceptors (isoprenaline), by direct enzyme
      activation (forskolin), or by inhibition of phosphodiesterase activity
      (papaverine), potently blocked both protein and DNA synthesis in cultured
      leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be
      involved in, or a consequence of, leiomyoma growth. The results also suggest a
      new interesting approach for leiomyoma pharmacotherapy.

PMID- 10956557
TI  - Detection of the immunoregulator p43-placental isoferritin in the human embryo
      and fetus.
AB  - Human placental isoferritin (PLF) is known to exert an immunosuppressive activity
      in vitro and is involved in the down-regulation of the maternal immune system
      during pregnancy. We have investigated the presence of PLF in the human embryo
      and early fetus and its secretion into amniotic fluid (AF) and fetal blood.
      Immunohistochemistry was performed on 25 normal embryos and fetuses, at 7-22
      weeks gestation, using the CM-H9 monoclonal antibody (mAb), generated
      specifically against the human p43-PLF protein. The amount of p43 was measured in
      AF of 81 fetuses at 11-22 weeks and in the blood of 19 fetuses at 15-22 weeks by
      means of an enzyme-linked immunosorbent assay with the same mAb. Positive p43-PLF
      immunostaining was found from 7 weeks gestation in proximal tubules of the
      primitive nephron and macrophages of the liver sinusoids, blood vessels and
      mesenchymal tissue. In the AF samples, p43-PLF was first detected at week 15
      gestation and thereafter steadily increased with advancing gestation whereas in
      fetal blood, p43-PLF was below or just above the lower limit of the assay. The
      gap between the first appearance of 43-PLF in embryonic tissue and its secretion
      into the amniotic fluid is probably linked to maturation of the renal function.
      The detection of the p43-PLF immunomodulator protein in macrophages at a very
      early stage of embryonic development and its very low concentration in fetal
      blood suggests that its immunoregulatory role is limited to the feto-maternal
      interface.

PMID- 10956558
TI  - Improvements of preimplantation diagnosis of aneuploidy by using microwave
      hybridization, cell recycling and monocolour labelling of probes.
AB  - Recent studies indicate that preimplantation genetic diagnosis of aneuploidy
      significantly reduces spontaneous abortions and increases pregnancy rates in
      women of advanced maternal age undergoing in-vitro fertilization. A new protocol
      was developed involving cell recycling (sequential hybridizations) and microwave
      hybridization of repetitive probes in order to obtain in a few hours enumeration
      results for chromosomes X, Y, 1, 13, 15, 16, 18, 21 and 22 in single blastomeres.
      The error rate using this protocol was significantly lower than in previous
      protocols and the analysis of nine chromosomes can be achieved in a shorter time
      than before.

PMID- 10956559
TI  - Detection of aneuploidy in chromosomes X, Y, 13, 18 and 21 by QF-PCR in 662
      selected pregnancies at risk.
AB  - A quantitative fluorescent-polymerase chain reaction (QF-PCR) test system with
      different short tandem repeat (STR) markers of the X chromosome (SBMA, DXS8377
      and DXS1283E) together with the amelogenin locus (AMXY) was developed for the
      rapid detection of sex chromosome aneuploidies on uncultured amniotic fluids. The
      samples (n = 662) were also tested with STRs specific for chromosomes 13, 18 or
      21, with two STRs used for each chromosome. In uninformative cases, an additional
      STR marker was applied. The QF-PCR data were compared with the results of
      conventional cytogenetics. One dark red stained specimen showed an artificial PCR
      pattern, probably due to maternal contamination. Six sex chromosome aberrations
      (four 45,X, one 47,XXY, one mosaic 47,XXY/46,XX) were identified as aneuploid by
      STRs specific for chromosome X and AMXY. One pregnancy with a mosaic 45, X/46,XX
      karyotype was not detected by the assay. In all, 12 cases with a numerical
      aberration involving either chromosome 18 or 21 or with a triploidy were
      correctly diagnosed by QF-PCR. No information was obtained in one fetal sample
      with a trisomy 18 due to an uncertain result for two of the three applied STRs
      specific for chromosome 18 and an uninformative third STR marker. Two samples
      with an unbalanced Robertsonian translocation could be identified by QF-PCR as
      trisomic for chromosomes 13 and 21 respectively. The results show an excellent
      agreement between QF-PCR and cytogenetics with regard to sex chromosome and
      autosomal aneuploidy detection in prenatal diagnosis.

PMID- 10956560
TI  - CAG trinucleotide repeats in the androgen receptor gene of infertile men exhibit
      stable inheritance in female offspring conceived after ICSI.
AB  - The androgen receptor (AR) gene is located on the X chromosome and contains a
      polymorphic CAG tract. CAG repeat expansions in the AR have been associated with
      male infertility and the neuromuscular disease, spinal bulbar muscular atrophy
      (SBMA). Based on Mendelian inheritance patterns, moderate CAG expansions in
      infertile men treated by intracytoplasmic sperm injection (ICSI) would be
      vertically transmitted to female offspring. Should further elongation of the
      repeat region occur in the male germline, it is conceivable that longer
      expansions could also be transmitted by ICSI and may lead to an increased
      incidence of male infertility and SBMA in succeeding generations. To determine
      the degree of stability of the paternal AR CAG tract following ICSI, we compared
      the CAG repeat number in the AR alleles of 92 men presenting for ICSI and their
      99 ICSI-conceived daughters. CAG repeat lengths in the AR alleles were determined
      by fluorescent polymerase chain reaction and Genescan analysis of amplification
      products separated on DNA sequencing gels. In the vast majority of cases (95 out
      of 99), we found that the AR CAG tracts ranging in size from 15-28 repeats
      exhibited stable inheritance in female offspring. However, in the remaining
      father-daughter pairs, there was a discordance in the expected inheritance
      pattern with evidence for both CAG expansion (20-->24; 22-->23) and contraction
      (26-->18 or 22) of the paternal AR allele. The detection of a low frequency of
      CAG mutation in paternal AR alleles following ICSI would be consistent with
      gonadal mosaicism originating from meiotic DNA replication errors. These findings
      in a typical group of infertile men undergoing ICSI for a variety of indications
      tend to alleviate concerns that ICSI may promote the transmission of AR alleles
      with expanded CAG tracts and suggest that the risk of SBMA in second generation
      sons would be extremely low.

PMID- 10956562
TI  - Calendar

PMID- 10956561
TI  - An end to Kraepelinian nosology?

PMID- 10956563
TI  - Binswanger's disease: an ongoing controversy.

PMID- 10956565
TI  - Can traumatic brain injury cause psychiatric disorders?
AB  - Traumatic brain injury (TBI) may cause psychiatric illness. This article reviews
      the evidence on the basis of an established set of causation criteria. The
      evidence is convincing for a strong association between TBI and mood and anxiety
      disorders. Substance abuse and schizophrenia are not strongly associated with
      TBI, and there is little research into the rates of personality disorders after
      TBI. Evidence for a biologic gradient is lacking, but such a gradient may not be
      relevant to TBI. Evidence for the correct temporal sequence is present.
      Preliminary evidence suggests a biologic rationale for TBI causing psychiatric
      illness. Further and methodologically improved research is supported and
      required.

PMID- 10956564
TI  - Vascular dementia and Alzheimer's disease: is there a difference? A comparison of
      symptoms by disease duration.
AB  - This study examined differences between vascular dementia (VaD) by the
      NINDS/AIRENS criteria and Alzheimer's disease (AD) on clinical grounds. A
      consecutive series of 517 patients with probable and possible VaD or AD were
      evaluated for cognitive, functional, and behavioral symptoms and separated into
      three subgroups by duration of dementia. These AD and VaD subgroups were then
      compared on a series of standardized clinical measures. The only consistent
      trends were for VaD patients to be more depressed, more functionally impaired,
      and less cognitively impaired within each disease duration subgroup. The authors
      conclude that there are few differences between clinically diagnosed VaD and AD.
      Subclassification of VaD into subgroups will improve the clinical utility of this
      nosologic entity.

PMID- 10956566
TI  - Sensitization phenomena in psychiatric illness: lessons from the kindling model.
AB  - Sensitization or "kindling-like" phenomena have been implicated in the
      pathophysiology of a number of psychiatric illnesses. A basic understanding of
      the prototypical sensitization phenomenon, the kindling model of epilepsy, is
      thus of increasing significance for the psychiatrist. This article presents a
      summary of the kindling model, with particular emphasis on glutamatergic
      mechanisms in general and plasticity of the N-methyl-D-aspartate (NMDA) receptor
      in specific. Findings from the kindling model are then discussed in light of
      their potential relevance to psychiatric illness. Finally, a speculative model is
      proposed in which opposing molecular processes lead to NMDA receptor
      hyperfunction in kindling and hypofunction in schizophrenia.

PMID- 10956567
TI  - Enlarged cavum septi pellucidi in patients with schizophrenia: clinical and
      cognitive correlates.
AB  - Enlarged cavum septi pellucidi (CSP) is a neurodevelopmental anomaly that has
      been associated with schizophrenia. This study was designed to evaluate, in
      patients with schizophrenia, the relationship between the severity of this
      anomaly and measures of symptom and cognitive skills. Three groups were used:
      patients with large CSP (n=14), patients without large CSP (n=14), and healthy
      control subjects (n=14). In patients with large CSP, a significant, inverse
      relationship was found between size of CSP and measures of cognitive deficit.
      Thus, the greater the size of the anomaly, the greater the cognitive deficit. No
      relationship was found between severity of CSP and symptom measures.

PMID- 10956568
TI  - Age disorientation in schizophrenia: an indicator of progressive and severe
      psychopathology, not institutional isolation.
AB  - The authors investigated age disorientation in chronic schizophrenia to determine
      whether specific symptomatic, neurologic, and cognitive disturbances were linked
      to its presentation. Disorientation to their age was detected in 30% (16/54) of
      the schizophrenic patients in a chronic care facility. In matched comparisons,
      age-disoriented patients showed lower educational achievement, poorer mental
      state performance, and a greater severity of symptoms, as well as more severe
      motor and sensory impairments. Levels of social withdrawal did not differentiate
      the two groups. A two-hit model consistent with neurodevelopmental and
      neurodegenerative processes is proposed to explain the data.

PMID- 10956569
TI  - Comparison of clinical and pathological phenotypes in two ethnically and
      geographically unrelated pedigrees segregating an equivalent presenilin 1
      mutation.
AB  - At least 30 different missense mutations have been identified within the
      presenilin 1 (PS1) gene in pedigrees transmitting familial Alzheimer's disease.
      The authors investigated the clinical and pathological features of affected
      members of two pedigrees segregating a PS1 Met146Leu mutation. Genetic
      relationships between these pedigrees can be effectively excluded on the basis of
      genealogical data and the fact that although the amino acid substitution is
      identical, the nucleotide mutations are different. The clinical picture shows
      remarkable similarities in the neurological and the neuropathological findings
      between the two pedigrees. This general clinical and pathological concordance
      argues that much of the disease phenotype arises directly from the effects of the
      amino acid substitution within the PS1 protein itself. Clinical differences could
      arise from a direct effect of the difference in base sequence or, alternatively,
      from the effect of genetic or environmental modifiers.

PMID- 10956570
TI  - Clozapine and risperidone treatment of psychosis in Parkinson's disease.
AB  - The authors compared efficacy and safety of risperidone and clozapine for the
      treatment of psychosis in a double-blind trial with 10 subjects with Parkinson's
      disease (PD) and psychosis. Mean improvement in the Brief Psychiatric Rating
      Scale psychosis score was similar in the clozapine and the risperidone groups
      (P=0.23). Although the mean motor Unified Parkinson's Disease Rating Scale score
      worsened in the risperidone group and improved in the clozapine group, this
      difference did not reach statistical significance. One subject on clozapine
      developed neutropenia. In subjects with PD, risperidone may be considered as an
      alternative to clozapine because it is as effective for the treatment of
      psychoses without the hematologic, antimuscarinic, and seizure side effects.
      However, risperidone may worsen extrapyramidal symptoms more than clozapine and
      therefore must be used with caution.

PMID- 10956571
TI  - SPECT findings in mentally retarded autistic individuals.
AB  - The authors examined specific deficits of cerebral blood perfusion in autistic
      patients as measured with [(99m)Tc]HMPAO single-photon emission computed
      tomography (SPECT). The study, conducted in an outpatient clinic setting,
      included a consecutive series of 30 patients with autism and 14 patients with
      mental retardation but no autism comparable in chronological age, mental age,
      height, weight, and head circumference. All participants were examined with a
      comprehensive psychiatric and neuropsychological battery and received a
      [(99m)Tc]HMPAO SPECT scan. Autistic patients had significantly lower perfusion
      than the control group in the following brain regions: right temporal lobe (basal
      and inferior areas), occipital lobes, thalami, and left basal ganglia. The study
      demonstrated significant perfusion deficits in specific brain areas of moderately
      to severely mentally retarded autistic patients.

PMID- 10956573
TI  - The role of pre-injury IQ in the determination of intellectual impairment from
      traumatic head injury.
AB  - The subjects were 17 head trauma patients whose pre-injury IQ and post-injury IQ
      scores on the Chinese Revised Version of the Wechsler Adult Intelligence Scale
      (WAIS-RC) were collected and analyzed. All patients had a neuroradiological
      imaging study. Changes in IQ scores were compared with neuroradiological findings
      and clinical determinations on the presence or absence of intellectual impairment
      from head trauma that were made by neuropsychiatrists without knowledge of pre
      injury IQ scores. Thirteen patients were clinically determined not to have
      suffered intellectual impairment, primarily because their post-injury IQs on the
      WAIS-RC were higher than 70. However, 3 of the 13 had significantly higher pre
      injury IQ scores, and they also showed brain damage on CT or MRI. Consideration
      of pre-injury IQ can improve the determination of intellectual impairment from
      head injury.

PMID- 10956572
TI  - How coil-cortex distance relates to age, motor threshold, and antidepressant
      response to repetitive transcranial magnetic stimulation.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a tool with antidepressant
      potential that uses a coil placed on the scalp to produce a powerful magnetic
      field that directly stimulates only the outermost cortex. MRI scans were obtained
      in 29 depressed adults involved in an rTMS antidepressant clinical treatment.
      These scans were analyzed to investigate the effect of distance from coil to
      cortex on clinical parameters. Longer motor cortex distance, but not prefrontal
      distance, strongly correlated with increased motor threshold (P<0.01). Clinical
      antidepressant response did not correlate with either distance. The rTMS
      antidepressant responders, however, were significantly younger (t=-2.430,
      P<0.05), and there appears to be a maximum threshold of age and distance to
      prefrontal cortex for response.

PMID- 10956574
TI  - Dementia associated with vitamin B(12) deficiency: presentation of two cases and
      review of the literature.
AB  - Vitamin B(12) deficiency has long been associated with a wide variety of
      hematological, neurological, and psychiatric disorders. The role of vitamin B(12)
      deficiency as one of the few treatable causes of dementia, however, is still
      controversial. The authors report on 2 elderly patients suffering from cognitive
      impairment and psychotic symptomatology probably related to cobalamin deficiency,
      who showed improvement after parenteral vitamin B(12) substitution. The
      literature concerning the pathophysiology and the diagnostic and therapeutic
      aspects of cobalamin deficiency is reviewed.

PMID- 10956575
TI  - Agitated symptom response to divalproex following acute brain injury.
AB  - This is the largest case series (N=29) to date describing divalproex for
      agitation symptoms. Chart information was abstracted retrospectively for all
      patients who received divalproex for agitation symptoms during a 22-month period
      in one inpatient brain injury rehabilitation unit. For 26 patients (90%),
      divalproex appeared effective within 7 days after a typical 1,250 mg/day dose.
      Most patients (93%) were discharged to their home or community sites. Divalproex
      appears to be an efficacious alternative to neuroleptics and benzodiazepines for
      alert, labile, impulsive, and disinhibited brain injury patients.

PMID- 10956576
TI  - The Kraepelinian dichotomy: evidence from developmental and neuroimaging studies.

PMID- 10956577
TI  - Neuropsychiatric consequences of traumatic brain injury: observations from Adolf
      Meyer.

PMID- 10956578
TI  - The anatomical facts and clinical varieties of traumatic insanity, 1904.

PMID- 10956580
TI  - In reply

PMID- 10956579
TI  - Rapidly progressive dementia and myoclonus.

PMID- 10956581
TI  - Hemi-inattention presenting as homonymous hemianopia in early dementia.

PMID- 10956582
TI  - Phenobarbital, propranolol, and aggression.

PMID- 10956583
TI  - Dietary intake of lead, cadmium, copper and zinc by children from the German
      North Sea island Amrum.
AB  - The dietary intake of metals was studied in seven male and seven female children
      at the age of 1.5 to 5.3 years living in a remote area of Germany, the North Sea
      island Amrum. The dietary intake of lead and cadmium was measured by a seven-day
      duplicate study using atomic absorption spectrometry. The dietary intake of
      copper and zinc were calculated from food diaries. The median lead and cadmium
      intakes were 2.1 micrograms/(kgbw x week) [range: 0.63-5.1 micrograms/(kgbw x
      week)] and 2.7 micrograms/(kgbw x week) [range: 1.7-4.4 micrograms/(kgbw x
      week)]. The median daily intake of copper and zinc were 1.1 mg/d (range: 0.54-2.5
      mg/d) and 5.7 mg/d (range: 2.7-14 mg/d). Compared to the provisional tolerable
      weekly intake (PTWI) of 25 micrograms/(kgbw x week) proposed by the WHO the
      dietary intake of lead was low. The median amounted to 8.5% and the maximum to
      20% of the PTWI. The cadmium intake was comparatively high. The median amounted
      to 39% and the maximum to 63% of the PTWI [7 micrograms/(kgbw x week)]. The
      median intake of copper was in the range of the values recommended by the German
      Society of Nutrition (0.7-1.0 mg/d and 1.0-1.5 mg/d for children at the age of 1
      < 4 years and 4-< 7 years). Twenty-three percent of the calculated intakes were
      below these values. The median intake of zinc however did not reach the
      recommended dietary intake of 7 and 10 mg/d for children at the age of 1-< 4
      years and 4-< 7 years.

PMID- 10956584
TI  - Helicobacter pylori prevalence in Leipzig's 1998 school entries: methodology and
      first results.
AB  - The non-invasive, stable-isotope-aided Helicobacter pylori (H. pylori) tests-
      breath and equivalent urine tests--were offered on a voluntary basis as part of
      the mandatory school entry medical examination to the 1998 school entry cohort of
      the City of Leipzig (480,000 residents). Parents of participating subjects were
      asked to fill out a detailed epidemiologic questionnaire. The response rate was
      94% (n = 2228 of 2369 school starters born in 1991/92). Parent-completed
      questionnaires were returned by 1890 (80%) children. The overall H. pylori
      positive prevalence was 7.2%. The prevalence among children with a test and a
      parent-completed questionnaire was 6.5%. Prevalences among subsequently tested
      family members of the positive tested children was 65, 60 and 39% for mothers,
      fathers and siblings respectively. Though studies have shown that the direct
      transmission of the bacterium (oral-oral and fecal-oral) is a dominant pathway of
      infection, the questionnaire analyses indicate associations between H. pylori
      colonisation and living as well as environmental conditions.

PMID- 10956585
TI  - Associations between duration of breast-feeding, sensitization to hens' eggs and
      eczema infantum in one and two year old children at high risk of atopy.
AB  - Through a cohort study, factors for the development of atopic disorders among
      children at high-risk of atopy were investigated by means of anamnesis, lifestyle
      factors and laboratory parameters. 475 high-risk children were selected out of
      the whole population of infants born within one year in the City and District of
      Leipzig. These 475 had an increased cord blood IgE (> 0.9 kU7l), double positive
      atopic family history (parents/siblings) or low birthweight (1500-2500 g).
      Questionnaires are answered regularly by the parents and the children are
      clinically examined annually. RESULTS: In the first and second year of life there
      has been a statistically significant correlation (p < 0.0001) between increased
      cord blood IgE and increased total IgE. At the age of one year we found eczema
      infantum in 51 out of 323 high-risk children. There was a significant association
      (p = 0.0001) between sensitization against hens' eggs and eczema. Infants who had
      been exclusively breast-fed > or = 5 months were more frequently sensitized to
      hens' egg and an eczema infantum was to diagnose more frequently. Significant
      differences in this respect were found within the risk groups, depending on
      family history of atopy and cord blood IgE. The duration of breast-feeding showed
      no correlation with sensitization to hens' eggs or atopy in two-year-olds.

PMID- 10956586
TI  - Effects of indoor painting and smoking on airway symptoms in atopy risk children
      in the first year of life results of the LARS-study. Leipzig Allergy High-Risk
      Children Study.
AB  - INTRODUCTION: The Leipzig Allergy High-Risk Children Study (LARS) is a
      prospective nested cohort control study about the influence of chemical indoor
      exposure in dwellings on the health outcome of atopy-risk children during the
      first years of life. DESIGN AND METHODS: 475 premature children and children with
      allergic risk factors have been selected out of the 1995/1996 birth cohort in the
      city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in
      the infant's bedrooms using passive sampling systems for 4 weeks after birth. The
      babies underwent a medical examination at the age of six weeks and 1 year. The
      parents answered a questionnaire. RESULTS: Correlations between VOC exposures and
      infections were calculated by multiple logistic regression. Selected VOC show a
      direct association to actually painted dwellings (OR = 2.4; 95% Cl 1.1-5.3). An
      increase of risk of pulmonary infections was observed in infants aged 6 weeks if
      restoration (painting OR 5.6; 95% Cl 1.3-24.0) or flooring connected with
      painting had occurred during the pregnancy period. Higher concentration of
      styrene (> 2.0 micrograms/m3, indicator for flooring) elevated the risk of
      pulmonary infections in six-week-old infants (OR = 2.1; 95% Cl 1.1-4.2).
      Environmental benzene > 5.6 micrograms/m3 increased the risk of airway infections
      in six-week-old babies (OR = 2.4; 95% Cl 1.28-4.48). Smoking in the dwelling (OR
      = 2.0; 95% Cl 1.1-3.5) as well as restoration (OR = 1.9; 95% Cl 1.1-3.5) are also
      risk factors of the development of wheezing in the one-year-old child.
      CONCLUSIONS: The data give indications in order to prevent allergies and chronic
      lung diseases in atopy risk children exposure to chemicals from indoor air should
      be minimised from birth on.

PMID- 10956587
TI  - Gas cooking, respiratory health and white blood cell counts in children.
AB  - The use of gas stoves has been associated with respiratory symptoms of chronic
      airway inflammation and higher rates of respiratory infections. We used data from
      a 1992/93 survey of 2,198 East German school children (aged 5 to 14) to assess
      whether gas cooking increases respiratory symptoms and is associated with a
      chronic inflammatory process reflected by an increase in white blood cell (WBC)
      count in children who do not exhibit signs of an acute respiratory infection. We
      found increases for the respiratory symptoms 'cough without cold' [odds ratio
      (OR) = 1.68; 95% confidence interval (CI), 1.18-2.39], 'cough in the morning' (OR
      = 1.58; CI, 1.23-2.04) and 'cough during the day or at night' (OR = 1.42; CI,
      1.13-1.78) in children living in homes with gas ranges, but lifetime prevalence
      of asthma, bronchitis, wheeze, and the prevalence of acute infections were not
      affected. Furthermore, we examined WBC levels in a subgroup of 1,134 children for
      whom blood samples were available and who did not suffer from an acute infection.
      We observed small increases in the risk of having WBC counts above the 75th or
      90th percentile (8300 or 9800 cell counts per microliter) when children were
      exposed to gas cooking after adjustment for age, gender, and passive smoking (OR
      = 1.30; CI, 0.98-1.73, and OR = 1.38; CI, 0.91-2.10). The strongest effect
      estimates for chronic inflammation were found for those children likely to have
      been exposed at higher levels, that is when stoves had no fans, in smaller homes,
      and for children spending more time indoors.

PMID- 10956588
TI  - Pathways and quantification of insoluble particles in the lung compartments of
      the rat.
AB  - The aim of this investigation was focused on mechanisms involved in
      toxicokinetics of particles and fibers within the rat lung. Biologically inert
      polystyrene particles or an asbestos--particle comixture were followed in their
      pathways of deposition and retention in the lung, particularly in the alveolar
      space and their accumulation in the lymph node tissue of exposed rats. One group
      of Wistar rats was intratracheally instilled with 0.4 ml phosphate buffered
      saline containing 2.4 x 10(8) inert polystyrene microspheres, a second group of
      animals was instilled with comixture containing 1.25 mg/ml of crocidolit asbestos
      fibers and previously prepared microspheres. Bronchoalveolar lavage of each lung
      was performed on post-instillation days 1, 7, 30, 80 and 150. Particles
      associated with alveolar phagocytes were counted using light microscopy. The lung
      and lymph node tissues were chemically dissolved and tissue aliquots passed
      through Nucleopor membrane filters. The number of particles in the tissue aliquot
      samples was determined using fluorescence microscopy. The results show that the
      fate of particulates in the respiratory system is highly dependent on the
      physical properties of the instilled material. Clearance patterns for particles
      and fibers are markedly different. Long-term consequences are the translocation
      and retention of fibrous material in the interstitum, involving the major route
      of clearance through the lymphatics.

PMID- 10956589
TI  - The influence of stressors on biochemical reactions--a review of present
      scientific findings with noise.
AB  - For every faculty of perception there is, according to the degree of irritation,
      a biochemical or psychobiological activation. This is also true for the
      perception of sound or noise. Initially, these processes allow for the adjustment
      of the organism to a changed situation (eustress). Prolonged effects of stressors
      may ultimately lead to regulatory disturbances and induce pathological processes
      (distress). The pathogenetic concept that psychobiological stresses (e.g. noise)
      may be connected with the well-known risk factors of cardiovascular diseases,
      through excitation of the central nervous system, is based on the known stress
      models. The central connective factors are the activation hormones of the adrenal
      gland, also referred to as stress hormones. From blood and urine parameters
      recorded in epidemiological and experimental studies under the influence of acute
      or chronic noise, a simplified model of the pathogenetic mechanism has been
      developed. Fundamental conditions for future assessing the "stress hormones" have
      been derived, by means of which premorbid conditions can be determined on a
      population or group basis.

PMID- 10956590
TI  - Value of acoustic rhinometry in environmental medicine.
AB  - It is a weak point of environmental medicine that health disturbances, e.g.
      functional affections of the upper respiratory tract, cannot be objectively
      judged by physicians resp. researchers. In this study, the validity of acoustic
      rhinometry, a method giving information on cross-sectional areas of the upper
      airways by means of ultrasound probing, was tested in 40 volunteers seven times
      during one year. Furthermore, using a simplified model of the nose the accuracy
      of this method to measure the minimal cross-sectional area (MCA) in the nose was
      tested. The measurements were extremely confounded by the mode of connection to
      the nose (e.g. selected adapter, direction of application) and by the MCA in the
      nasal cavity. Statistical analyses showed a good reproducibility of measurements
      repeated within minutes, but suggested an intrapersonal variability over the
      analyzed examination phases due to apparatus independent factors. However, this
      variability could not be explained by influencing and confounding factors
      obtained by questionnaire, medical history, and physical examination. The test
      model showed little to great errors (1.5 to 568.5%) between the actual and the
      measured MCA, depending on the diameter. It is concluded that the method of
      acoustic rhinometry has to be standardized before it's value for environmental
      medicine can finally be judged. Further studies are necessary that should focus
      among others on factors influencing the variability of MCA and the effect of MCA
      on the measurement of the area behind the MCA. So far, the use of acoustic
      rhinometry for the evaluation of nasal function cannot be recommended.

PMID- 10956591
TI  - August Gartner and building, housing and communal hygiene 100 years of housing
      hygiene in Jena.
AB  - August Gartner who had been called to the first Chair of Hygiene in Jena in 1886
      has provided impulses decisive for the development of hygiene in the fields of
      construction, housing and communities. He has formulated important requirements
      for indoor climate, e.g. for heating, ventilation, indoor air temperature, indoor
      air humidity, avoidance of temperature asymmetry and thermal insulation of
      houses. His requirements to ensure adequate insulation, e.g. a ratio between
      window area and floor area of 1:8-1:10, have remained valid until today. Missing
      attention to his findings with regard to sewage disposal gained on the occasions
      of two typhoid outbreaks in Jena as early as in 1901 and 1915 resulted in the
      last water-borne typhoid outbreak in Germany in 1980, in the same place.

PMID- 10956592
TI  - Further studies on thermal resistance of bovine parvovirus against moist and dry
      heat.
AB  - To supplement the results of thermal resistance of bovine parvovirus (Haden
      strain, BPV) published previously, we carried out assays at 60 degrees C (moist
      heat) to compare the thermal resistance of BPV with that of hepatitis B-virus
      (HBV). What we know about the resistance of HBV at a temperature of 60 degrees C
      is mainly based on data collected within the context of blood product
      pasteurization. The results suggest that at a temperature of 60 degrees C, BPV
      shows thermal resistance comparable to HBV. Thus, BPV--which is easier to handle-
      can be considered a good test virus to verify the efficacy of thermal
      disinfection techniques against HBV. BPV is very resistant against dry heat of
      100 degrees C, the inactivation largely depending upon the residual moisture of
      the lyophilisate. Reducing the residual moisture from 2% to less than 1%, the
      exposure time has to be prolonged by ca. 2.5 times to achieve the same virucidal
      effect.

PMID- 10956593
TI  - Rapid identification of Enterobacteriaceae using a novel 23S rRNA-targeted
      oligonucleotide probe.
AB  - The aim of this study was to rapidly identify bacteria of the family of
      Enterobacteriaceae using fluorescent in situ hybridization (FISH). A comparative
      sequence analysis was carried out and a 23S rRNA signature sequence for
      Enterobacteriaceae was identified. A 23S rRNA-targeted oligonucleotide probe
      (EBAC1790) was constructed and subsequently tested against 40 reference strains.
      Nearly all of the Enterobacteriaceae used in this study yielded positive results
      with EBAC1790, except for Edwardsiella tarda (ATCC 15947). None of the non
      Enterobacteriaceae reference strains gave positive signals with the probe. The
      possibility of a rapid detection of Enterobacteriaceae in groundwater was
      demonstrated using colony hybridization.

PMID- 10956594
TI  - Intestinal cell adhesion and maximum growth temperature of psychrotrophic
      aeromonads from surface water.
AB  - Investigation of 650 Aeromonas strains taken from surface water--used as a source
      of drinking water--and from the associated drinking water treatment plants has
      demonstrated that only a small proportion of the strains are endowed with
      intestinal cell adhesion and growth at 39 degrees C; these characteristics are
      concurrently encountered in Aeromonas strains from clinical material. The
      investigations permit the conclusion that even the Aeromonas species, of which
      certain strains are pathogenic to human, cannot generally be viewed as being
      potentially pathogenic.

PMID- 10956595
TI  - Impact of silver and copper on the survival of amoebae and ciliated protozoa in
      vitro.
AB  - The efficacy of 1:10 silver/copper combinations for inactivation of Hartmannella
      vermiformis amoebas and the ciliated protozoan Tetrahymena pyriformis in vitro
      was studied. Tetrahymena and Hartmannella/isolate 19 were inactivated for 2 log
      steps by 100 + 1000 micrograms/l Ag + Cu. Hartmannella/isolate 21 was more
      resistant. 500 + 5000 micrograms/l produced only a 0.6 log reduction. The
      investigations clearly showed that levels within the limit of the German drinking
      water regulation (10 + 100 micrograms/l Ag + Cu) could not inactivate these
      protozoas in vitro.

PMID- 10956596
TI  - ?

PMID- 10956598
TI  - [ [In Process Citation]

PMID- 10956597
TI  - [PRIMARY STENT IMPLANTATION IN AORTIC COARCTATION. MID-TERM FOLLOW-UP]
AB  - The use of balloon-expandable stents provides an effective alternative therapy in
      patients with stenotic lesions in congenital heart disease. Stents implantation
      has served to improve the results and to reduce complications of balloon
      angioplasty for coarctation and recoarctation of the aorta. AIM: We report our
      results after primary stents implantation for coarctation and recoarctation of
      the aorta. PATIENTS AND METHODS: Balloon-expandable stents were implanted in 14
      patients (mean age 20 +/- 12 years) with coarctation of the aorta (11 native and
      3 postoperative); 2 patients had associated malformations. The morphology varied:
      10 resembled a located-diaphragm (one of them with moderate arch hypoplasia); 2
      had distorted coarctation and 2 had a complete aortal obstruction. Five patients
      were hypertensive and 1 had cardiogenic shock and severe arrhythmias which did
      not respond to intensive medical therapy. In all cases 14 Palmaz stents (7 P308
      and 7 P4014) were implanted with the primary technique through a Mullin's sheath.
      The balloon-to-descending aorta diameter ratio, measured at the level of the
      diaphragm, was 1. A special technique was carried out in the 2 cases with
      complete aortal obstruction. RESULTS: The procedure was effective in all 14
      cases. The coarctation diameter increased from 4 +/- 2 to 15 +/- 2 mm (p <
      0.0001) and transcoarctation systolic pressure gradient decreased from 43 +/- 19
      to 2 +/- 2 mmHg (p < 0.0001). The ratio of the coarctation to descending aorta
      diameter measured at the level of the diaphragma increased from 0.3 +/- 0.1 to
      0.95 +/- 0.05 (p < 0.001). At 19 +/- 8 months follow up, all patients showed
      sustained clinical improvement. The patient with complete aortal obstruction
      experienced a dramatic improvement, but she died from a sudden cardiac event 22
      months after the procedure. At angiographic follow up in 7 patients, 1 year after
      implantation, no recoarctation was observed with secondary vessels patent, and
      absence of restenosis. CONCLUSIONS: a) Percutaneous endovascular stents
      implantation in coarctation and recoarctation of the aorta may become an
      effective treatment modality in the older child, adolescent and adults; b) stents
      are particulary attractive in those patients with a more complex anatomy and
      higher surgical risk; c) primary stenting is expected to have a lower rate of
      complications, and d) we describe a special technique with a right femoral-left
      humeral arterial circuit that is successfully applied to patients with complete
      aortal obstruction.

PMID- 10956599
TI  - [Early results with partial left ventriculectomy (the Batista operation)].
AB  - INTRODUCTION AND OBJECTIVES: The shortage of donors as well as the morbidity and
      mortality associated with transplantation have led to development of other
      surgical options for end-stage dilated cardiomyopathy. Partial left
      ventriculectomy reducing ventricular diameter and mass has been proposed. We here
      in report the initial experience (not only limited to the alternative of
      transplantation) and immediate results obtained with this technique in our
      institution. METHODS: Six patients with dilated cardiomyopathy underwent surgery:
      4 of idiopathic origin with exclusion criteria for heart transplantation and 2 of
      valvular or mixed etiology. Resection of a slice of the left ventricle was
      performed between the two papillary muscles, from the apex of the heart to the
      mitral annulus, and closure was carried out with a single suture with mitral
      annuloplasty in 5 cases (tricuspid repair in one and aortic valve replacement in
      two). RESULTS: An intraaortic balloon pump was required in two patients; one died
      from cardiogenic shock and the other died after several ventricular arrhythmias
      fifteen days after surgery. Intraoperative echocardiographic studies showed a
      significant reduction in both diastolic diameter (8.7 to 6.8 cm; p = 0.02) and
      mitral insufficiency and an increase in the ejection fraction (17 to 27%; p =
      0.09) which were maintained on echography 10 days after surgery. CONCLUSIONS:
      This technique is a feasible, suitable therapeutic option for refractory
      congestive heart failure. Appropriate patient selection, the perioperative
      management and long-term support remain to be defined.

PMID- 10956600
TI  - [Obstructive myocardiopathic hypertrophy and sequential atrioventricular
      stimulation. Immediate results and long term follow-up. Seven years experience].
AB  - BACKGROUND: Sequential pacing as a primary treatment for patients with severe
      hypertrophic obstructive cardiomyopathy is still under controversy. In this study
      we sought to evaluate the effects of pacing on left ventricular systolic and
      diastolic function, its repercussion on pathophysiology and the possible changes
      in clinical evolution and functional class in patients who didn't respond to
      medical therapy. PATIENTS AND METHODS: Thirty-four patients with severe
      hypertrophic obstructive cardiomyopathy in functional class III-IV underwent
      evaluation. The mean age was 64 +/- 11 years. Sixty-two per cent were over 65.
      The study protocol included Holter monitoring, baseline echo-Doppler, during
      pacing, at 6 months and at the end of follow-up, and a complete catheterization
      and coronary angiography. Mean follow-up time was 36 +/- 20 month (range 6-74).
      In four patients sequential pacing was ineffective and the protocol had to be
      discontinued. Thirty patients received a permanent dual-chamber pacemaker and
      systolic and diastolic function were evaluated by hemodynamic, angiographic and
      eco-Doppler studies. RESULTS: Long-term stimulation reduced the subaortic
      gradient from 95 +/- 38 to 39 +/- 28 mmHg (p < 0.001), left ventricular systolic
      pressure from 207 +/- 38 to 164 +/- 30 mmHg (p < 0.001) and left ventricular end
      diastolic pressure from 23 +/- 7 to 14 +/- 5 mmHg (p < 0.001), pulmonary
      capillary wedge pressure from 19 +/- 7 to 14 +/- 5 mmHg (p < 0.001), ejection
      fraction from 79 +/- 6 to 71 +/- 6% (p < 0.001) and mitral insufficiency.
      Diastolic function improved with an increase in early filling from 39 +/- 11 to
      52 +/- 10% (p < 0.001) and E/A relation from 0.93 +/- 0.4 to 1.6 +/- 0.8 (p <
      0.001), and a reduction in late filling from the left ventricle from 36 +/- 10%
      to 24 +/- 10% (p < 0.001). The speed of the E wave increased from 0.83 +/- 0.3 to
      0.92 +/- 0.3 (p < 0.001) and we observed a reduction of the A wave from 93 +/-
      0.3 to 0.66 +/- 0.2 (p < 0.001), pressure-half time from 95 +/- 34 to 66 +/- 19
      ms (p < 0.001) and we observed deceleration time from 320 +/- 90 to 221 +/- 57 (p
      < 0.01). All patients have improved their functional class, allowing a reduction
      in pharmacological therapy. Two exitus of cardiological origin occurred.
      CONCLUSIONS: Sequential AV pacing in selected patients with severe hypertrophic
      obstructive cardiomyopathy can reduce subaortic gradient, pulmonary capillary
      wedge, left ventricular filling pressures and the severity of mitral
      regurgitation, and improve the markedly altered diastolic function. The
      significant symptomatic improvement allows a reduction in medical treatment.
      Thus, it represents a viable alternative to open-heart surgery, particularly in
      elderly patients, with lower morbidity and mortality rates.

PMID- 10956601
TI  - [Intracoronary stents in small vessels: short- and long-term clinical results].
AB  - OBJECTIVE: To assess the clinical outcome of coronary stenting in small vessels
      (< 3 mm), using high pressure balloon inflation and antithrombotic therapy.
      PATIENTS AND METHODS: Vessel size was evaluated as < or >= 3 mm at the time of
      procedure and measured at a level of maximum diameter. We studied 234 consecutive
      patients with placement of 300 stents in 279 lesions, comprising 84 stents
      implanted in 79 lesions located at small vessels (< 3 mm). The standard technique
      included high pressure balloon inflation (15.8 +/- 2.2 atm) and post-stenting
      therapy with ticlopidine and aspirin for one month. Mean clinical follow-up was
      17.6 +/- 10 months. RESULTS: Procedural success without in-hospital major events
      was similar between small and large vessels (93.7 in vessels of < 3 mm vs 93.5%
      in vessels of >= 3 mm; p = NS). Three small vessels presented subacute stent
      thrombosis, whereas no thrombotic occlusion occurred in large vessels (3.8 vs 0%;
      p = 0.006). At two years, small vessels had a lower target lesion
      revascularization free survival (73.6 vs 90.3%; p < 0.001). After adjustment for
      variables previously described as predictors of stent restenosis, in multivariate
      analysis, a small vessel of < 3 mm was an independent predictor of target lesion
      revascularization (p = 0.001). Although patients with stenting in small vessels
      did not differ significantly in terms of any cause death (4.6 vs 3.8%; p = 0.7)
      nor acute myocardial infarction (2.9 vs 1.1%; p = 0.3), event-free survival was
      significantly lower after two years (69.1 vs 86.6%; p < 0.001). CONCLUSIONS: As
      compared to large vessels, coronary stenting in small vessels was performed with
      similar rates of initial success, however they had a significantly worse clinical
      long-term outcome in terms of subacute stent thrombosis and target lesion
      revascularization at follow-up.

PMID- 10956602
TI  - [Lipoprotein (a) as a predictor of severity of coronary artery stenosis
      documented by angiography in male coronary patients under 50 years old].
AB  - OBJECTIVE: To determine the relationship between lipoprotein (a) seric levels
      with the age of coronary artery disease debut and the severity of coronary
      lesions in a group of male patients less than 50 years old. PATIENTS AND METHODS:
      We studied a group of 230 male patients, younger than 50 who were consecutively
      admitted to the hospital because of an ischemic coronary event. During
      hospitalization, the lipoprotein (a) in plasma was measured in all patients. They
      were distributed in two groups according to age at time of coronary disease
      clinical presentation with a cut off age of 40. A group of 142 patients underwent
      a cardiac catheterism and coronariography due to clinical or electrical
      unstability. RESULTS: The lipoprotein (a) levels were related with the number of
      diseased vessels. In this way lipoprotein (a) levels were 12 mg/dl (1.5-75) in
      those patients showing a normal coronariography; 27 mg/dl (2. 5-96) in those with
      one vessel disease; 34 mg/dl (7-90) in those with two vessels affected and 63
      mg/dl (2-116) in the case of three-vessel disease, with statistical significance
      of p = 0.003. No significant differences in lipoprotein (a) levels were found
      when the age of coronary artery disease presentation was taken into account. In
      this way lipoprotein (a) levels were 31 mg/dl (2-97) in patients younger than 40
      years of age, in comparison to 33 mg/dl (2-94) in those older than 40.
      CONCLUSIONS: In our community male patients with a diagnosis of coronary artery
      disease and less than 50 years old showed a relationship between lipoprotein (a)
      levels and the severity and number of coronary vessel diseases. However, an
      association between lipoprotein (a) levels with the age of coronary disease
      presentation was not evident.

PMID- 10956603
TI  - [The capacity of the rest-dobutamine gated SPECT protocol to predict contractile
      recovery after revascularization of myocardial dysinergic areas].
AB  - INTRODUCTION AND AIM: Gated-SPECT is a promising method to analyze myocardial
      viability. We have assessed the accuracy of a new protocol of rest/Dobutamine
      gated-SPECT, based on the evaluation of contractile reserve induced by 10
      microg/kg/min of Dobutamine, to predict contractile recovery after
      revascularization of dysinergic myocardial territories. PATIENTS AND METHODS: In
      a group of 36 patients submitted to percutaneous revascularization, we selected
      40 vascular territories (21 left descending artery, 19 right coronary-circumflex)
      with severely depressed contractility (contrast ventriculography, center line
      method). Follow up evaluation at 6 months showed the absence of angiographic
      restenosis and control contrast ventriculography assessed the contractile changes
      of the selected territories, considering those with contractile restoration as
      viable. Before revascularization, rest/Dobutamine gated-SPECT study was applied
      and viability was defined as the presence of contractile reserve (positive or
      improvement [n = 21] and negative or impairment [n = 7]) with non viability being
      the absence of contractile reserve (n = 12). We analyzed the evolution of the
      ejection fraction in a group of 27 patients with impaired ventricular function
      and complete revascularization. RESULTS: Gated-SPECT showed a sensitivity of 0.96
      (95% CI 0.78-0.99) and a specificity of 0.78 (95% CI 0.48-0.94) in the diagnosis
      of viability. The ejection fraction (median [interquartile range]) increased
      after revascularization: 0.42 (0.15) vs 0.55 (0.22), Z = -3.9; p < 0. 001. The
      diagnosis of viability by gated-SPECT (p < 0.001) and the extent of severely
      depressed myocardium (p = 0.04) independently predicted the increase of the
      ejection fraction after revascularization. CONCLUSIONS: The analysis of
      contractile reserve by rest/Dobutamine gated-SPECT is adequate to diagnose
      viability in territories with severely depressed contractility and independently
      predicts the increase of ejection fraction after revascularization.

PMID- 10956606
TI  - [ [In Process Citation]

PMID- 10956604
TI  - [Guidelines of the Spanish Society of Cardiology for clinical practice in
      exercise testing].
AB  - Most exercise testing is performed in adults with known or suspected ischemic
      heart disease. In the last few years cardiac imaging techniques have been applied
      in this field, improving the information obtained with the procedure. However,
      the exceptions to this rule are emerging rapidly not only in healthy people
      (asymptomatic individuals, athletes, handicapped people) but also in cardiac
      patients (advanced congestive heart failure, hypertension, rhythm disorders,
      congenital heart disease, etc.). All the-se issues justify the need for a
      multidisciplinary consensus document in Spain. This paper reviews and updates the
      methodological aspects of the stress test, including those related to oxygen
      consumption measurements. The main aim of this review was to determine the role
      of exercise testing in the evaluation of ischemic heart disease as well as the
      applications of imaging stress testing. The usefulness of this test in other non
      ischemic cardiac disorders and in selected subsets of healthy people is also
      reviewed.

PMID- 10956605
TI  - [Guidelines of the Spanish Society of Cardiology for cardiovascular disease
      prevention and cardiac rehabilitation].
AB  - The priorities for the prevention of cardiovascular diseases should be focused on
      patients with established disease and high risk subjects, with individual global
      risk always being taken into account. The current evidence on the influence of
      the main risk factors are unanimous (dyslipemia, tobacco, hypertension and
      diabetes mellitus), being somewhat less so in cases of sedentarism, obesity and
      the metabolic syndrome. The evidence concerning other risk factors still remains
      controversial. Guidelines for the control of the different risk factors should be
      based on the evidence derived from both epidemiological or clinical trials. The
      recommendations published by several scientific societies should also be
      followed. There are, at present, important evidence on the efficacy of smoking
      cessation, the treatment of arterial hypertension and particularly on the
      successful control of lipid levels with lipid-lowering drugs, especially with
      statins. There is also evidence on the need for rigorous control of diabetic
      patients not only in relation to the glucose levels but also to dyslipemia. The
      most efficient measures for a reduction in morbidity and mortality are cessation
      of smoking, appropriate hypertensive therapy, a comprehensive program of cardiac
      rehabilitation and overall the successful control of lipid levels with statins.

PMID- 10956607
TI  - [Hemodynamic benefits of left ventricular pacing in two pacemakers syndromes with
      refractory heart failure].
AB  - We describe two cases in which right ventricular pacing produced severe
      hemodynamic deterioration and in which changing the pacing from the right to the
      left ventricle sharply corrected these alterations, while simultaneous
      biventricular pacing did not. Chronic left ventricular pacing can solve
      hemodynamic alterations in severe pacemaker syndromes, thereby avoiding the need
      for mitral prosthesis implantation in some cases. The use of this procedure today
      should be individualized, including acute hemodynamic and echocardiographic
      studies, because the width of the QRS complex during pacing is not a significant
      predictor of hemodynamic efficiency.

PMID- 10956608
TI  - [Atrial septal aneurysms. Presentation of three cases].
AB  - Atrial septal aneurysm is a saccular formed dilation of the tissue, generally
      located at the level of the fossa ovalis, which protrudes to the right or the
      left atrium or both. With the use of transesophageal echocardiography it has
      become more easily and more frequently identified in patients. The prevalence of
      atrial septal aneurysm, with transesophageal echocardiography, is between 2% and
      10% in adults. In the pediatric patient population, the prevalence is 0.9% to
      1.7% in children and 4.9% in infants. Atrial septal aneurysm has been associated
      with congenital heart diseases, with acquired heart diseases, and more recently
      with cerebrovascular events of embolic origin, including transient ischemic
      attacks and acute cerebrovascular accidents.

PMID- 10956609
TI  - [Intermittent pre-excitation after adenosine administration].
AB  - We describe a case of 2:1 intermittent preexcitation after adenosine
      administration in a patient with an accessory pathway that did not show
      preexcitation on the basal ECG. We review the mechanisms involved that explain
      this event and the possible utility of adenosine to show accessory pathways that
      do not show preexcitation on the ECG.

PMID- 10956611
TI  - [A 49 year old patient with single left ventricular morphology who underwent
      surgical repair and good outcome ].
AB  - We report a 51-year-old patient, diagnosed with single left ventricle and
      anterior rudimentary chamber which was corrected by a Fontan procedure in 1997.
      The echocardiogram, Holter and pulmonary perfusion scintigraphy, isotopic
      ventriculography, magnetic resonance and blood tests performed during follow-up
      showed an uncomplicated postoperative course. The patient remains asymptomatic.
      We believe that this is the oldest case suffering from this anomaly who underwent
      surgical repair.

PMID- 10956612
TI  - [Acromegaly associated with mitral and tricuspid prolapse. Report of a case].
AB  - A 65 year-old male with severe systolic mitral and tricuspid valve prolapse,
      associated with long-standing acromegaly is reported. The non published
      association could be caused by the effect of growth hormone on the valve
      connective tissue.

PMID- 10956610
TI  - [Complications of transesophageal echocardiography with dobutamine].
AB  - The transesophageal echocardiographic approach improves the diagnostic power of
      transthoracic stress echocardiography. However, it is a seminvasive test and its
      safety is not well established. Our objective was to compare the incidence of
      complications of transesophageal and transthoracic dobutamine echocardiography.
      We collected data from 63 patients with inadequate transthoracic window, who
      underwent transesophageal dobutamine echocardiography and were compared with 100
      patients in whom the transthoracic approach was diagnostic. Baseline blood
      pressure and heart rate were higher in the first group. There were no differences
      in those parameters at the end of the test. Neither were atropine administration
      and side effects more frequent in any of the groups. There were no cases of
      ventricular fibrillation, ventricular tachycardia, acute myocardial infarction,
      intractable angina or intolerance to the probe. Side effects were equally present
      in both groups. Transesophageal dobutamine stress echocardiography is a safe test
      that can be used in patients with coronary artery disease and poor transthoracic
      window.

PMID- 10956613
TI  - Lung redox homeostasis: emerging concepts.
AB  - This symposium was organized to present some aspects of current research
      pertaining to lung redox function. Focuses of the symposium were on roles of
      pulmonary endothelial NADPH oxidase, xanthine oxidase (XO)/xanthine dehydrogenase
      (XDH), heme oxygenase (HO), transplasma membrane electron transport (TPMET), and
      the zinc binding protein metallothionein (MT) in the propagation and/or
      protection of the lung or other organs from oxidative injury. The presentations
      were chosen to reflect the roles of both intracellular (metallothionein, XO/XDH,
      and HO) and plasma membrane (NADPH oxidase, XO/XDH, and unidentified TPMET) redox
      proteins in these processes. Although the lung endothelium was the predominant
      cell type under consideration, at least some of the proposed mechanisms operate
      in or affect other cell types and organs as well.

PMID- 10956614
TI  - Mechanisms regulating endothelial cell barrier function.
AB  - Endothelium forms a physical barrier that separates blood from tissue.
      Communication between blood and tissue occurs through the delivery of molecules
      and circulating substances across the endothelial barrier by directed transport
      either through or between cells. Inflammation promotes macromolecular transport
      by decreasing cell-cell and cell-matrix adhesion and increasing centripetally
      directed tension, resulting in the formation of intercellular gaps. Inflammation
      may also increase the selected transport of macromolecules through cells.
      Significant progress has been made in understanding the molecular and cellular
      mechanisms that account for constitutive endothelial cell barrier function and
      also the mechanisms activated during inflammation that reduce barrier function.
      Current concepts of mechanisms regulating endothelial cell barrier function were
      presented in a symposium at the 2000 Experimental Biology Conference and are
      reviewed here.

PMID- 10956615
TI  - Apoptosis in lung pathophysiology.
AB  - As recently as 1993, fewer than 10 manuscripts had been published on the topic of
      apoptosis specifically in the lung. Although that number is increasing, far fewer
      papers appear each year on apoptosis in the lung than in the other major organs.
      Therefore, our knowledge of this important aspect of lung cell physiology is
      relatively rudimentary. Recent literature is beginning to define important roles
      for apoptosis in normal lung cell turnover, lung development, and the
      pathogenesis of diseases such as interstitial pulmonary fibrosis, acute
      respiratory distress syndrome, and chronic obstructive pulmonary disease.
      Although the involvement of lung cell apoptosis in each of these examples seems
      clear, the many factors comprising the normal and abnormal regulation of cell
      death remain to be elucidated and are likely to be different in each situation.
      The definition of those factors will be an exciting and challenging field of
      research for many years to come. In that context, the goal of this symposium was
      to discuss, from a physiological perspective, some of the most recent and
      exciting advances in the definition of signaling mechanisms involved in the
      regulation of apoptosis specifically in lung cell populations.

PMID- 10956616
TI  - Protein kinase C isozymes and the regulation of diverse cell responses.
AB  - Individual protein kinase C (PKC) isozymes have been implicated in many cellular
      responses important in lung health and disease, including permeability,
      contraction, migration, hypertrophy, proliferation, apoptosis, and secretion. New
      ideas on mechanisms that regulate PKC activity, including the identification of a
      novel PKC kinase, 3-phosphoinositide-dependent kinase-1 (PDK-1), that regulates
      phosphorylation of PKC, have been advanced. The importance of targeted
      translocation of PKC and isozyme-specific binding proteins (like receptors for
      activated C-kinase and caveolins) is well established. Phosphorylation state and
      localization are now thought to be key determinants of isozyme activity and
      specificity. New concepts on the role of individual PKC isozymes in proliferation
      and apoptosis are emerging. Opposing roles for selected isozymes in the same cell
      system have been defined. Coupling to the Wnt signaling pathway has been
      described. Phenotypes for PKC knockout mice have recently been reported. More
      specific approaches for studying PKC isozymes and their role in cell responses
      have been developed. Strengths and weaknesses of different experimental
      strategies are reviewed. Future directions for investigation are identified.

PMID- 10956617
TI  - The conundrum of oxidant-induced barrier dysfunction.

PMID- 10956618
TI  - Involvement of c-Src in diperoxovanadate-induced endothelial cell barrier
      dysfunction.
AB  - Reactive oxygen species (ROS) generated by activated leukocytes play an important
      role in the disruption of endothelial cell (EC) integrity, leading to barrier
      dysfunction and pulmonary edema. Although ROS modulate cell signaling,
      information remains limited regarding the mechanism(s) of ROS-induced EC barrier
      dysfunction. We utilized diperoxovanadate (DPV) as a model agent to explore the
      role of tyrosine phosphorylation in the regulation of EC barrier function. DPV
      disrupted EC barrier function in a dose-dependent manner. Tyrosine kinase
      inhibitors, genistein, and PP-2, a specific inhibitor of Src, reduced the DPV
      mediated barrier dysfunction. Consistent with these results, DPV-induced Src
      activation was attenuated by PP-2. Furthermore, DPV increased the association of
      Src with cortactin and myosin light chain kinase, indicating their potential role
      as cytoskeletal targets for Src. Transient overexpression of either wild-type Src
      or a constitutively active Src mutant potentiated the DPV-mediated decline in
      barrier dysfunction, whereas a dominant negative Src mutant attenuated the
      response. These studies provide the first direct evidence for Src involvement in
      DPV-induced EC barrier dysfunction.

PMID- 10956619
TI  - Regulation and function of CCSP during pulmonary Pseudomonas aeruginosa infection
      in vivo.
AB  - Clara cell secretory protein (CCSP) is a 16-kDa homodimeric polypeptide secreted
      by respiratory epithelial cells in the conducting airways of the lung. To assess
      the role of CCSP in bacterial inflammation and to discern whether CCSP expression
      is influenced by bacterial infection, CCSP-deficient [(-/-)] gene-targeted mice
      and wild-type mice were given Pseudomonas aeruginosa intratracheally.
      Infiltration by polymorphonuclear cells was significantly increased in the lungs
      of CCSP(-/-) mice 6 and 24 h after the administration of the bacteria. The number
      of viable bacteria isolated from the lungs in CCSP(-/-) mice was decreased
      compared with that in wild-type mice. Concentrations of the proinflammatory
      cytokines interleukin-1beta and tumor necrosis factor-alpha were modestly
      increased after 6 and 24 h, respectively, in CCSP(-/-) mice. The concentration of
      CCSP protein in lung homogenates decreased for 1-5 days after infection and
      recovered by 14 days after infection. Likewise, CCSP mRNA and immunostaining for
      CCSP markedly decreased in respiratory epithelial cells after infection. CCSP
      deficiency was associated with enhanced pulmonary inflammation and improved
      killing of bacteria after acute pulmonary infection with P. aeruginosa. The
      finding that Pseudomonas infection inhibited CCSP expression provides further
      support for the concept that CCSP plays a role in the modulation of pulmonary
      inflammation during infection and recovery.

PMID- 10956620
TI  - VEGF, fetal liver kinase-1, and permeability increase during unilateral lung
      ischemia.
AB  - Vascular endothelial growth factor (VEGF) is a potent mediator of increased
      vascular permeability and an endothelial cell mitogen. Because VEGF is
      upregulated during ventilated ischemia of isolated lungs and may lead to both
      increased vascular permeability and neovascularization, we hypothesized that VEGF
      and kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/flk-1)
      expression would increase acutely after unilateral pulmonary arterial (PA)
      ischemia in vivo in association with evidence of endothelial cell barrier
      dysfunction. To test this hypothesis, VEGF and KDR/flk-1 mRNA and protein
      expression were measured after 4, 8, and 24 h of left PA ligation in mice.
      Permeability was assessed at the same time points by measurement of
      bronchoalveolar lavage protein concentration and lung wet-to-dry weight ratios.
      Results were compared with those from uninstrumented and sham-operated mice. VEGF
      and KDR/flk-1 protein in the left lung both increased by 4 h and then returned to
      baseline, whereas increased VEGF and KDR/flk-1 mRNA expression was sustained
      throughout 24 h of unilateral ischemia. Bronchoalveolar lavage protein
      concentration increased transiently during ischemia, whereas wet-to-dry weight
      ratio of the left lung increased more slowly and remained elevated after 24 h of
      left PA ligation. These results suggest that increased expression of VEGF and
      KDR/flk-1 during unilateral PA occlusion in mice may contribute to the
      development of acute lung injury in this model.

PMID- 10956621
TI  - Surfactant metabolism in SP-D gene-targeted mice.
AB  - Mice with surfactant protein (SP)-D deficiency have three to four times more
      surfactant lipids in air spaces and lung tissue than control mice. We measured
      multiple aspects of surfactant metabolism and function to identify abnormalities
      resulting from SP-D deficiency. Relative to saturated phosphatidylcholine (Sat
      PC), SP-A and SP-C were decreased in the alveolar surfactant and the large
      aggregate surfactant fraction. Although large-aggregate surfactant from SP-D gene
      targeted [(-/-)] mice converted to small-aggregate surfactant more rapidly,
      surface tension values were comparable to values for surfactant from SP-D wild
      type [(+/+)] mice. (125)I-SP-D was cleared with a half-life of 7 h from SP-D(-/-)
      mice vs. 13 h in SP-D(+/+) mice. Although initial incorporation and secretion
      rates for [(3)H]palmitic acid and [(14)C]choline into Sat PC were similar, the
      labeled Sat PC was lost from the lungs of SP-D(+/+) mice more rapidly than from
      SP-D(-/-) mice. Clearance rates of intratracheal
      [(3)H]dipalmitoylphosphatidylcholine were used to estimate net clearances of Sat
      PC, which were approximately threefold higher for alveolar and total lung Sat PC
      in SP-D(-/-) mice than in SP-D(+/+) mice. SP-D deficiency results in multiple
      abnormalities in surfactant forms and metabolism that cannot be attributed to a
      single mechanism.

PMID- 10956622
TI  - Substance P-induced airway hyperreactivity is mediated by neuronal M(2) receptor
      dysfunction.
AB  - Neuronal muscarinic (M(2)) receptors inhibit release of acetylcholine from the
      vagus nerves. Hyperreactivity in antigen-challenged guinea pigs is due to
      blockade of these M(2) autoreceptors by eosinophil major basic protein (MBP)
      increasing the release of acetylcholine. In vivo, substance P-induced
      hyperactivity is vagally mediated. Because substance P induces eosinophil
      degranulation, we tested whether substance P-induced hyperreactivity is mediated
      by release of MBP and neuronal M(2) receptor dysfunction. Pathogen-free guinea
      pigs were anesthetized and ventilated. Thirty minutes after intravenous
      administration of [Sar(9),Met(O(2))(11)]- substance P, guinea pigs were
      hyperreactive to vagal stimulation and M(2) receptors were dysfunctional. The
      depletion of inflammatory cells with cyclophosphamide or the administration of an
      MBP antibody or a neurokinin-1 (NK(1)) receptor antagonist (SR-140333) all
      prevented substance P-induced M(2) dysfunction and hyperreactivity. Intravenous
      heparin acutely reversed M(2) receptor dysfunction and hyperreactivity. Thus
      substance P releases MBP from eosinophils resident in the lungs by stimulating
      NK(1) receptors. Substance P-induced hyperreactivity is mediated by blockade of
      inhibitory neuronal M(2) receptors by MBP, resulting in increased release of
      acetylcholine.

PMID- 10956624
TI  - The PDE inhibitor zaprinast enhances NO-mediated protection against vascular
      leakage in reperfused lungs.
AB  - Disruption of endothelial barrier properties with development of noncardiogenic
      pulmonary edema is a major threat in lung ischemia-reperfusion (I/R) injury that
      occurs under conditions of lung transplantation. Inhaled nitric oxide (NO)
      reduced vascular leakage in lung I/R models, but the efficacy of this agent may
      be limited. We coadministered NO and zaprinast, a cGMP-specific phosphodiesterase
      inhibitor, to further augment the NO-cGMP axis. Isolated, buffer-perfused rabbit
      lungs were exposed to 4.5 h of warm ischemia. Reperfusion provoked a transient
      elevation in pulmonary arterial pressure and a negligible rise in microvascular
      pressure followed by a massive increase in the capillary filtration coefficient
      and severe lung edema formation. Inhalation of 10 parts/million of NO or
      intravascular application of 100 microM zaprinast on reperfusion both reduced
      pressor response and moderately attenuated vascular leakage. Combined
      administration of both agents induced no additional vasodilation at constant
      microvascular pressures, but additively protected against capillary leakage
      paralleled by a severalfold increase in perfusate cGMP levels. In conclusion,
      combining low-dose NO inhalation and phosphodiesterase inhibition may be suitable
      for the maintenance of graft function in lung transplantation by amplifying the
      beneficial effect of the NO-cGMP axis and avoiding toxic effects of high NO
      doses.

PMID- 10956623
TI  - Role of diminished epithelial GM-CSF in the pathogenesis of bleomycin-induced
      pulmonary fibrosis.
AB  - Evidence derived from human and animal studies strongly supports the notion that
      dysfunctional alveolar epithelial cells (AECs) play a central role in determining
      the progression of inflammatory injury to pulmonary fibrosis. We formed the
      hypothesis that impaired production of the regulatory cytokine granulocyte
      macrophage colony-stimulating factor (GM-CSF) by injured AECs plays a role in the
      development of pulmonary fibrosis. To test this hypothesis, we used the well
      characterized model of bleomycin-induced pulmonary fibrosis in rats. GM-CSF mRNA
      is expressed at a constant high level in the lungs of untreated or saline
      challenged animals. In contrast, there is a consistent reduction in expression of
      GM-CSF mRNA in the lung during the first week after bleomycin injury. Bleomycin
      treated rats given neutralizing rabbit anti-rat GM-CSF IgG develop increased
      fibrosis. Type II AECs isolated from rats after bleomycin injury demonstrate
      diminished expression of GM-CSF mRNA immediately after isolation and in response
      to stimulation in vitro with endotoxin compared with that in normal type II
      cells. These data demonstrate a defect in the ability of type II epithelial cells
      from bleomycin-treated rats to express GM-CSF mRNA and a protective role for GM
      CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis.

PMID- 10956625
TI  - Thrombin stimulates the expression of PDGF in lung epithelial cells.
AB  - Several growth factors, including platelet-derived growth factor (PDGF), have
      been implicated in the mechanism of lung and airway remodeling. In the present
      study, we evaluated whether thrombin may promote lung and airway remodeling by
      increasing PDGF production from lung and airway epithelial cells. Conditioned
      medium (CM) was prepared by treating epithelial cells with increasing
      concentrations of thrombin; before use in the assays, CM was treated with hirudin
      until complete inhibition of thrombin activity. CM from epithelial cells
      stimulated the proliferation of lung fibroblasts and bronchial smooth muscle
      cells. Anti-PDGF antibody significantly inhibited this CM proliferative activity,
      implicating PDGF in this effect. Enzyme immunoassay and RT-PCR demonstrated that
      thrombin induced the secretion and expression of PDGF from bronchial and alveolar
      epithelial cells. RT-PCR showed that epithelial cells express the thrombin
      receptors protease-activated receptor (PAR)-1, PAR-3, and PAR-4. The PAR-1
      agonist peptide was also found to induce PDGF secretion from epithelial cells,
      suggesting that the cellular effect of thrombin occurs via a PAR-1-mediated
      mechanism. Overall, this study showed for the first time that thrombin may play
      an important role in the process of lung and airway remodeling by stimulating the
      expression of PDGF via its cellular receptor, PAR-1.

PMID- 10956626
TI  - Hypoxia reduces atrial natriuretic peptide clearance receptor gene expression in
      ANP knockout mice.
AB  - We tested the hypotheses that hypoxic exposure is associated with exacerbated
      pulmonary hypertension and right ventricular (RV) enlargement, reduced atrial
      natriuretic peptide (ANP) clearance receptor (NPR-C) expression, and enhanced B
      type natriuretic peptide (BNP) expression in the absence of ANP. Male wild-type
      [ANP(+/+)], heterozygous [ANP(+/-)], and homozygous [ANP(-/-)] mice were studied
      after a 5-wk hypoxic exposure (10% O(2)). Hypoxia increased RV ANP mRNA and
      plasma ANP levels only in ANP(+/+) and ANP(+/-) mice. Hypoxia-induced increases
      in RV pressure were significantly greater in ANP(-/-) than in ANP(+/+) or ANP(+/
      ) mice (104 +/- 17 vs. 45 +/- 10 and 63 +/- 7%, respectively) as were increases
      in RV mass (38 +/- 4 vs. 26 +/- 5 and 29 +/- 4%, respectively). NPR-C mRNA levels
      were greatly reduced in the kidney, lung, and brain by hypoxia in all three
      genotypes. RV BNP mRNA and lung and kidney cGMP levels were increased in hypoxic
      mice. These findings indicate that disrupted ANP expression worsens hypoxic
      pulmonary hypertension and RV enlargement but does not alter hypoxia-induced
      decreases in NPR-C and suggest that compensatory increases in BNP expression
      occur in the absence of ANP.

PMID- 10956627
TI  - Regulation of diaphragmatic nitric oxide synthase expression during hypobaric
      hypoxia.
AB  - Nitric oxide (NO) is normally synthesized inside skeletal muscle fibers by both
      endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases. In this study, we
      evaluated the influence of hypobaric hypoxia on the expression of NOS isoforms,
      argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and manganese
      superoxide dismutase (Mn SOD) in the ventilatory muscles. Rats were exposed to
      hypobaric hypoxia ( approximately 95 mmHg) from birth for 60 days or 9-11 mo. Age
      matched control groups of rats also were examined. Sixty days of hypoxia elicited
      approximately two- and ninefold increases in diaphragmatic eNOS and nNOS protein
      expression (evaluated by immunoblotting), respectively, and about a 50% rise in
      diaphragmatic NOS activity. In contrast, NOS activity and the expression of these
      proteins declined significantly in response to 9 mo of hypoxia. Hypoxia elicited
      no significant alterations in AS, AL and Mn SOD protein expression. Moreover, the
      inducible NOS (iNOS) was not detected in normoxic and hypoxic diaphragmatic
      samples. We conclude that diaphragmatic NOS expression and activity undergo
      significant adaptations to hypobaric hypoxia and that iNOS does not participate
      in this response.

PMID- 10956628
TI  - Attenuation of lung reperfusion injury after transplantation using an inhibitor
      of nuclear factor-kappaB.
AB  - A central role for nuclear factor-kappaB (NF-kappaB) in the induction of lung
      inflammatory injury is emerging. We hypothesized that NF-kappaB is a critical
      early regulator of the inflammatory response in lung ischemia-reperfusion injury,
      and inhibition of NF-kappaB activation reduces this injury and improves pulmonary
      graft function. With use of a porcine transplantation model, left lungs were
      harvested and stored in cold Euro-Collins preservation solution for 6 h before
      transplantation. Activation of NF-kappaB occurred 30 min and 1 h after transplant
      and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate
      (PDTC), a potent inhibitor of NF-kappaB, given to the lung graft during organ
      preservation (40 mmol/l) effectively inhibited NF-kappaB activation and
      significantly improved lung function. Compared with control lungs 4 h after
      transplant, PDTC-treated lungs displayed significantly higher oxygenation, lower
      PCO(2), reduced mean pulmonary arterial pressure, and reduced edema and cellular
      infiltration. These results demonstrate that NF-kappaB is rapidly activated and
      is associated with poor pulmonary graft function in transplant reperfusion
      injury, and targeting of NF-kappaB may be a promising therapy to reduce this
      injury and improve lung function.

PMID- 10956629
TI  - Myeloperoxidase and protein oxidation in cystic fibrosis.
AB  - Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and
      progressive lung dysfunction, possibly associated with the formation of
      neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens
      from adult CF patients were analyzed for MPO characteristic protein modifications
      and found to contain large amounts of active MPO as well as high levels of
      protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result
      from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum
      levels of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), indicating local production
      of nitric oxide (NO. ), were not elevated but in fact were slightly reduced in
      CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in
      CF sputum compared with controls, reflecting the formation of reactive nitrogen
      intermediates, possibly through MPO-catalyzed oxidation of NO(2)(-). CF sputum
      MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured
      tracheobronchial epithelial cells; however, peroxidase-dependent protein
      oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO
      derived oxidants by CF mucus and perhaps formation of secondary cytotoxic
      products within CF sputum. Our findings demonstrate the formation of MPO-derived
      oxidizing and possibly nitrating species within the respiratory tract of subjects
      with CF, which collectively may contribute to bronchial injury and respiratory
      failure in CF.

PMID- 10956631
TI  - Matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in fetal
      rabbit lung.
AB  - Cell-extracellular matrix interaction and extracellular matrix remodeling are
      known to be important in fetal lung development. We investigated the localization
      of matrix metalloproteinases (MMPs) in fetal rabbit lungs. Immunohistochemistry
      for type IV collagen, MMP-1, MMP-2, MMP-9, membrane type (MT) 1 MMP, and tissue
      inhibitor of metalloproteinase (TIMP)-2 and in situ hybridization for MMP-9 mRNA
      were performed. Gelatin zymography and Western blotting for MT1-MMP in lung
      tissue homogenates were also studied. MMP-1 and MT1-MMP were detected in
      epithelial cells, and MMP-2 and TIMP-2 were detected in epithelial cells and some
      mesenchymal cells in each stage. MMP-9 was found in epithelial cells mainly in
      the late stage. Gelatin zymography revealed that the ratio of active MMP-2 to
      latent MMP-2 increased dramatically during the course of development. MT1-MMP was
      detected in tissue homogenates, especially predominant in the late stage. These
      findings suggest that MMPs and their inhibitors may contribute to the formation
      of airways and alveoli in fetal lung development and that activated MMP-2 of
      alveolar epithelial cells may function to provide an extremely wide alveolar
      surface.

PMID- 10956630
TI  - Endothelin receptor blockade decreases lung water in young rats exposed to viral
      infection and hypoxia.
AB  - Viral respiratory infections may increase the susceptibility of young animals to
      hypoxia-induced pulmonary edema. Because hypoxia stimulates endothelin
      production, we hypothesized that an increase in lung endothelin contributes to
      these alterations in lung water. Weanling rats were infected with Sendai virus,
      causing a mild respiratory infection. At day 7 after infection, animals were
      exposed to hypoxia (inspired O(2) fraction = 0.1) for 24 h. Exposure to virus
      plus hypoxia led to increases in lung water compared with control groups (P <
      0.001). Lung endothelin levels were significantly higher in the virus plus
      hypoxia group than in control groups (P < 0.001). A second group of infected
      animals received bosentan, a nonselective endothelin receptor antagonist, during
      exposure to hypoxia. Bosentan-treated animals showed less lung water
      accumulation, less lung lavage fluid protein, and less perivascular fluid cuffing
      than untreated animals (P < 0.01). We conclude that the combination of a recent
      viral respiratory infection and exposure to moderate hypoxia led to increases in
      endothelin in the lungs of young rats and that endothelin receptor blockade
      ameliorates the hypoxia-induced increases in lung water found in these animals.

PMID- 10956633
TI  - Genetic susceptibility to irritant-induced acute lung injury in mice.
AB  - Recent studies suggest that genetic variability can influence irritant-induced
      lung injury and inflammation. To begin identifying genes controlling
      susceptibility to inhaled irritants, seven inbred mouse strains were continuously
      exposed to nickel sulfate (NiSO(4)), polytetrafluoroethylene, or ozone (O(3)),
      and survival time was recorded. The A/J (A) mouse strain was sensitive, the
      C3H/He (C3) strain was intermediate, and the C57BL/6 (B6) strain was resistant to
      NiSO(4)-induced acute lung injury. The B6AF(1) offspring were also resistant. The
      strain sensitivity pattern for NiSO(4) exposure was similar to that of
      polytetrafluoroethylene or ozone (O(3)). Pulmonary pathology was comparable for A
      and B6 mice. In the A strain, 15 microg/m(3) of NiSO(4) produced 20% mortality.
      The strain sensitivity patterns for lavage fluid proteins (B6 > C3 > A) and
      neutrophils (A >/= B6 > C3) differed from those for acute lung injury. This
      phenotype discordance suggests that these traits are not causally linked (i.e.,
      controlled by independent arrays of genes). As in acute lung injury, B6C3F(1)
      offspring exhibited phenotypes (lavage fluid proteins and neutrophils) resembling
      those of the resistant parental strain. Agreement of acute lung injury strain
      sensitivity patterns among irritants suggested a common mechanism, possibly
      oxidative stress, and offspring resistance suggested that sensitivity is
      inherited as a recessive trait.

PMID- 10956632
TI  - TIMP-1, -2, -3, and -4 in idiopathic pulmonary fibrosis. A prevailing
      nondegradative lung microenvironment?
AB  - Fibroblast proliferation and extracellular matrix accumulation characterize
      idiopathic pulmonary fibrosis (IPF). We evaluated the presence of tissue
      inhibitor of metalloproteinase (TIMP)-1, -2, -3, and -4; collagenase-1, -2, and 
      3; gelatinases A and B; and membrane type 1 matrix metalloproteinase (MMP) in 12
      IPF and 6 control lungs. TIMP-1 was found in interstitial macrophages and TIMP-2
      in fibroblast foci. TIMP-3 revealed an intense staining mainly decorating the
      elastic lamina in vessels. TIMP-4 was expressed in IPF lungs by epithelial and
      plasma cells. TIMP-2 colocalized with Ki67 in fibroblasts, whereas TIMP-3
      colocalized with p27 in inflammatory and epithelial cells. Collagenase-1 was
      localized in macrophages and alveolar epithelial cells, collagenase-2 was
      localized in a few neutrophils, and collagenase-3 was not detected. MMP-9 was
      found in neutrophils and subepithelial myofibroblasts. Myofibroblast expression
      of MMP-9 was corroborated in vitro by RT-PCR. MMP-2 was noticed in
      myofibroblasts, some of them close to areas of basement membrane disruption, and
      membrane type 1 MMP was noticed in interstitial macrophages. These findings
      suggest that in IPF there is higher expression of TIMPs compared with
      collagenases, supporting the hypothesis that a nondegrading fibrillar collagen
      microenvironment is prevailing.

PMID- 10956634
TI  - Adherence of adoptively transferred alloreactive Th1 cells in lung: partial
      dependence on LFA-1 and ICAM-1.
AB  - T helper type 1 (Th1) cells are important effectors in a number of immune
      mediated lung diseases. We recently described a murine model of lung injury
      induced by adoptive transfer of cloned alloreactive Th1 cells. To investigate
      mechanisms that result in injury to the lung, we studied the in vivo distribution
      of (51)Cr-labeled Th1 cells. One hour after intravenous administration, >85% of
      injected radioactivity was left in the lung, and at 24 h, 40% of radioactivity
      was left in the lung. Adherence of Th1 cells in the lung was significantly
      inhibited by neutralizing antibody to lymphocyte function-associated antigen-1.
      Th1 cell adherence also was decreased in lungs of mice deficient in intercellular
      adhesion molecule-1 (ICAM-1). Th1 cell transfer further induced expression of
      ICAM-1 and vascular cell adhesion molecule-1 in the lung. Vascular cell adhesion
      molecule-1-immunoreactive protein was markedly induced in lung endothelium by
      alloreactive Th1 cells. These findings indicate that Th1 cells localize in normal
      lung by a mechanism involving lymphocyte function-associated antigen-1 and ICAM
      1. Alloreactive cells further induce endothelial adhesion molecules that may
      facilitate recruitment of inflammatory cells to the lung and amplify Th1 cell
      induced lung injury.

PMID- 10956635
TI  - Chemokine expression in Th1 cell-induced lung injury: prominence of IFN-gamma
      inducible chemokines.
AB  - Proinflammatory responses generated by T helper type 1 (Th1) cells may contribute
      significantly to immune-mediated lung injury. We describe a murine model of Th1
      cell-induced lung injury in which adoptive transfer of alloreactive Th1 cells
      produces pulmonary inflammation characterized by mononuclear cell vasculitis,
      alveolitis, and interstitial pneumonitis. To investigate the link between
      activation of Th1 cells in the lung and inflammatory cell recruitment, we
      characterized cytokine and chemokine mRNA expression in Th1 cells activated in
      vitro and in lung tissue after adoptive transfer of Th1 cells. Activated Th1
      cells per se express mRNA for interferon (IFN)-gamma and several members of the
      tumor necrosis factor family as well as the C-C chemokine receptor-5 ligands
      regulated on activation normal T cells expressed and secreted and macrophage
      inflammatory protein-1alpha and -1beta. Additional chemokine genes were induced
      in the lung after Th1 cell administration, most notably IFN-gamma-inducible
      protein (IP-10) and monokine induced by IFN-gamma (MIG). Remarkable increases in
      IP-10- and MIG-immunoreactive proteins were present in inflammatory foci lung and
      identified in macrophages, endothelium, bronchial epithelium, and alveolar
      structures. The findings suggest that IFN-gamma-inducible chemokines are an
      important mechanism for amplifying inflammation initiated by Th1 cells in the
      lung.

PMID- 10956636
TI  - Inhibition of angiogenesis decreases alveolarization in the developing rat lung.
AB  - To determine whether angiogenesis is necessary for normal alveolarization, we
      studied the effects of two antiangiogenic agents, thalidomide and fumagillin, on
      alveolarization during a critical period of lung growth in infant rats. Newborn
      rats were treated with daily injections of fumagillin, thalidomide, or vehicle
      during the first 2 wk of life. Compared with control treatment, fumagillin and
      thalidomide treatment reduced lung weight-to-body weight ratio and pulmonary
      arterial density by 20 and 36%, respectively, and reduced alveolarization by 22%.
      Because these drugs potentially have nonspecific effects on lung growth, we also
      studied the effects of Su-5416, an inhibitor of the vascular endothelial growth
      factor receptor known as kinase insert domain-containing receptor/fetal liver
      kinase (KDR/flk)-1. As observed with the other antiangiogenic agents, Su-5416
      treatment decreased alveolarization and arterial density. We conclude that
      treatment with three different antiangiogenic agents attenuated lung vascular
      growth and reduced alveolarization in the infant rat. We speculate that
      angiogenesis is necessary for alveolarization during normal lung development and
      that injury to the developing pulmonary circulation during a critical period of
      lung growth can contribute to lung hypoplasia.

PMID- 10956637
TI  - TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF
      kappaB-dependent mechanism.
AB  - Tumor necrosis factor (TNF)-alpha is released from alveolar macrophages after
      phagocytosis of mineral fibers. To determine whether TNF-alpha affects the
      binding of fibers to epithelial cells, we exposed rat tracheal explants to TNF
      alpha or to culture medium alone, followed by a suspension of amosite asbestos or
      fiberglass (MMVF10). Loosely adherent fibers were removed from the surface with a
      standardized washing technique, and the number of bound fibers was determined by
      scanning electron microscopy. Increasing doses of TNF-alpha produced increases in
      fiber binding. This effect was abolished by an anti-TNF-alpha antibody, the
      proteasome inhibitor MG-132, and the nuclear factor (NF)-kappaB inhibitor
      pyrrolidine dithiocarbamate. Gel shift and Western blot analyses confirmed that
      TNF-alpha activated NF-kappaB and depleted IkappaB in this system and that these
      effects were prevented by MG-132 and pyrrolidine dithiocarbamate. These
      observations indicate that TNF-alpha increases epithelial fiber binding by a NF
      kappaB-dependent mechanism. They also suggest that mineral particles may cause
      pathological lesions via an autocrine-like process in which the response evoked
      by particles, for example, macrophage TNF-alpha production, acts to enhance
      subsequent interactions of particles with tissue.

PMID- 10956638
TI  - Hetero-concatemeric KIR6.X4/SUR14 channels display distinct conductivities but
      uniform ATP inhibition.
AB  - K(IR)6.1 and K(IR)6.2 are the pore-forming subunits of K(NDP)(,) the nucleotide
      diphosphate-activated K(ATP) channels, and classical K(ATP) channels,
      respectively. "Hybrid" channels, in which the structure is predetermined by
      concatemerizing K(IR)6.1 and K(IR)6.2, exhibit distinct conductivities specified
      by subunit number and position. Inclusion of one K(IR)6.2 is sufficient to open
      K(IR)6. X-X-X-X/SUR1(4) in the absence of nucleotide stimulation through
      sulfonylurea receptor-1 (SUR1). ATP inhibited the spontaneous bursting of hybrid
      channels with an IC(50(ATP)) approximately 10(-)(5) m, similar to that of
      K(IR)6.2(4)-containing channels. These findings and a transient increase in
      K(NDP) channel activity following rapid wash-out of MgATP suggested that K(IR)6.1
      is not ATP-insensitive as previously believed. We propose that SUR-dependent,
      inhibitory ATP-enhanced interactions of the cytoplasmic domains of both K(IR)6.1
      and K(IR)6.2 stabilize a closed form of the M2 bundle in the gating apparatus.

PMID- 10956639
TI  - Histidine phosphorylation of annexin I in airway epithelia.
AB  - Although [Cl(-)](i) regulates many cellular functions including cell secretion,
      the mechanisms governing these actions are not known. We have previously shown
      that the apical membrane of airway epithelium contains a 37-kDa phosphoprotein
      (p37) whose phosphorylation is regulated by chloride concentration. Using metal
      affinity (chelating Fe(3+)-Sepharose) and anion exchange (POROS HQ 20)
      chromatography, we have purified p37 from ovine tracheal epithelia to
      electrophoretic homogeneity. Sequence analysis and immunoprecipitation using
      monoclonal and specific polyclonal antibodies identified p37 as annexin I, a
      member of a family of Ca(2+)-dependent phospholipid-binding proteins. Phosphate
      on [(32)P]annexin I, phosphorylated using both [gamma-(32)P]ATP and [gamma
      (32)P]GTP, was labile under acidic but not alkaline conditions. Phosphoamino acid
      analysis showed the presence of phosphohistidine. The site of phosphorylation was
      localized to a carboxyl-terminal fragment of annexin I. Our data suggest that
      cAMP and AMP (but not cGMP) may regulate annexin I histidine phosphorylation. We
      propose a role for annexin I in an intracellular signaling system involving
      histidine phosphorylation.

PMID- 10956640
TI  - Interaction of luminal calcium and cytosolic ATP in the control of type 1
      inositol (1,4,5)-trisphosphate receptor channels.
AB  - Ca(2+) within intracellular stores (luminal Ca(2+)) is believed to play a role in
      regulating Ca(2+) release into the cytosol via the inositol (1,4,5)-trisphosphate
      (Ins(1,4,5)P(3))-gated Ca(2+) channel (or Ins(1,4,5)P(3) receptor). To
      investigate this, we incorporated purified Type 1 Ins(1,4,5)P(3) receptor from
      rat cerebellum into planar lipid bilayers and monitored effects at altered
      luminal [Ca(2+)] using K(+) as the current carrier. At a high luminal [Ca(2+)]
      and in the presence of optimal [Ins(1,4,5)P(3)] and cytosolic [Ca(2+)], a short
      burst of Ins(1,4,5)P(3) receptor channel activity was followed by complete
      inactivation. Lowering the luminal [Ca(2+)] caused the channel to reactivate
      indefinitely. At luminal [Ca(2+)], reflecting a partially empty store, channel
      activity did not inactivate. The addition of cytosolic ATP to a channel
      inactivated by high luminal [Ca(2+)] caused reactivation. We provide evidence
      that luminal Ca(2+) is exerting its effects via a direct interaction with the
      luminal face of the receptor. Activation of the receptor by ATP may act as a
      device by which cytosolic Ca(2+) overload is prevented when the energy state of
      the cell is compromised.

PMID- 10956641
TI  - Thyroid hormone regulates carnitine palmitoyltransferase Ialpha gene expression
      through elements in the promoter and first intron.
AB  - Carnitine palmitoyltransferase I (CPT-I) catalyzes the transfer of long chain
      fatty acyl groups from CoA to carnitine for translocation across the
      mitochondrial inner membrane. CPT-Ialpha is a key regulatory enzyme in the
      oxidation of fatty acids in the liver. CPT-Ialpha is expressed in all tissues
      except skeletal muscle and adipose tissue, which express CPT-Ibeta. Expression of
      CPT-Ialpha mRNA and enzyme activity are elevated in the liver in hyperthyroidism,
      fasting, and diabetes. CPT-Ialpha mRNA abundance is increased 40-fold in the
      liver of hyperthyroid compared with hypothyroid rats. Here, we examine the
      mechanisms by which thyroid hormone (T3) stimulates CPT-Ialpha gene expression.
      Four potential T3 response elements (TRE), which contain direct repeats separated
      by four nucleotides, are located 3000-4000 base pairs 5' to the start site of
      transcription in the CPT-Ialpha gene. However, only one of these elements
      functions as a TRE. This TRE binds the T3 receptor as well as other nuclear
      proteins. Surprisingly, the first intron of the CPT-Ialpha gene is required for
      the T3 induction of CPT-Ialpha expression, but this region of the gene does not
      contain a TRE. In addition, we show that CPT-Ialpha is induced by T3 in cell
      lines of hepatic origin but not in nonhepatic cell lines.

PMID- 10956643
TI  - Molecular characterization of CRMP5, a novel member of the collapsin response
      mediator protein family.
AB  - The CRMP (collapsin response mediator protein) family is thought to play key
      roles in growth cone guidance during neural development. The four members (CRMP1
      4) identified to date have been demonstrated to form hetero-multimeric structures
      through mutual associations. In this study, we cloned a novel member of this
      family, which we call CRMP5, by the yeast two-hybrid method. This protein shares
      relatively low amino acid identity with the other CRMP members (49-50%) and also
      with dihydropyrimidinase (51%), whereas CRMP1-4 exhibit higher identity with each
      other (68-75%), suggesting that CRMP5 might be categorized into a third
      subfamily. The mouse CRMP5 gene was located at chromosome 5 B1. Northern blot and
      in situ hybridization analyses indicated that CRMP5 is expressed throughout the
      nervous system similarly to the other members (especially CRMP1 and CRMP4) with
      the expression peak in the first postnatal week. Association experiments using
      the yeast two-hybrid method and co-immunoprecipitation showed that CRMP5
      interacts with dihydropyrimidinase and all the CRMPs including itself, except for
      CRMP1, although the expression profile almost overlaps with that of CRMP1 during
      development. These results suggest that CRMP complexes in the developing nervous
      system are classifiable into two populations that contain either CRMP1 or CRMP5.
      This indicates that different complexes may have distinct functions in shaping
      the neural networks.

PMID- 10956642
TI  - A pollen-specific novel calmodulin-binding protein with tetratricopeptide
      repeats.
AB  - Calcium is essential for pollen germination and pollen tube growth. A large body
      of information has established a link between elevation of cytosolic Ca(2+) at
      the pollen tube tip and its growth. Since the action of Ca(2+) is primarily
      mediated by Ca(2+)-binding proteins such as calmodulin (CaM), identification of
      CaM-binding proteins in pollen should provide insights into the mechanisms by
      which Ca(2+) regulates pollen germination and tube growth. In this study, a CaM
      binding protein from maize pollen (maize pollen calmodulin-binding protein,
      MPCBP) was isolated in a protein-protein interaction-based screening using (35)S
      labeled CaM as a probe. MPCBP has a molecular mass of about 72 kDa and contains
      three tetratricopeptide repeats (TPR) suggesting that it is a member of the TPR
      family of proteins. MPCBP protein shares a high sequence identity with two
      hypothetical TPR-containing proteins from Arabidopsis. Using gel overlay assays
      and CaM-Sepharose binding, we show that the bacterially expressed MPCBP binds to
      bovine CaM and three CaM isoforms from Arabidopsis in a Ca(2+)-dependent manner.
      To map the CaM-binding domain several truncated versions of the MPCBP were
      expressed in bacteria and tested for their ability to bind CaM. Based on these
      studies, the CaM-binding domain was mapped to an 18-amino acid stretch between
      the first and second TPR regions. Gel and fluorescence shift assays performed
      with CaM and a CaM-binding synthetic peptide further confirmed MPCBP binding to
      CaM. Western, Northern, and reverse transcriptase-polymerase chain reaction
      analysis have shown that MPCBP expression is specific to pollen. MPCBP was
      detected in both soluble and microsomal proteins. Immunoblots showed the presence
      of MPCBP in mature and germinating pollen. Pollen-specific expression of MPCBP,
      its CaM-binding properties, and the presence of TPR motifs suggest a role for
      this protein in Ca(2+)-regulated events during pollen germination and growth.

PMID- 10956644
TI  - Stimulation of cellular sphingomyelin import by the chemokine connective tissue
      activating peptide III.
AB  - The selective import of phospholipids into cells could be mediated by proteins
      secreted from the cells into the extracellular compartment. We observed that the
      supernatants obtained from suspensions of thrombin-activated platelets stimulated
      the exchange of pyrene (py)-labeled sphingomyelin between lipid vesicles in
      vitro. The proteins with sphingomyelin transfer activity were purified and
      identified as the chemokine connective tissue-activating peptide III (CTAP-III)
      and platelet basic protein. Isolated CTAP-III stimulated the exchange of py
      sphingomyelin between lipid vesicles but did not affect the translocations of py
      labeled phosphatidylcholine and phosphatidylethanolamine. CTAP-III rapidly
      increased the transfer of py-sphingomyelin from low density lipoproteins into
      peripheral blood lymphocytes, other immune cells, and fibroblasts. In the
      presence of heparin, CTAP-III was unable to insert sphingomyelin into the
      peripheral blood lymphocytes. The activation energy of the py-sphingomyelin
      transfer suggested that the translocation proceeded entirely in a hydrophobic
      environment. [(3)H]Sphingomyelin transferred to the cells by CTAP-III was
      hydrolyzed to [(3)H]ceramide and [(3)H]sphingosine after activation with tumor
      necrosis factor alpha. The generation of the [(3)H]sphingolipid messengers was
      catalyzed by acid sphingomyelinase. Our results identify CTAP-III as the first
      mediator of the selective (endocytosis-independent) cellular import of
      sphingomyelin allowing the paracrine modulation of the sphingolipid signaling.

PMID- 10956645
TI  - The integrins alpha3beta1 and alpha6beta1 physically and functionally associate
      with CD36 in human melanoma cells. Requirement for the extracellular domain OF
      CD36.
AB  - Lateral association between different transmembrane glycoproteins can serve to
      modulate integrin function. Here we characterize a physical association between
      the integrins alpha(3)beta(1) and alpha(6)beta(1) and CD36 on the surface of
      melanoma cells and show that ectopic expression of CD36 by CD36-negative MV3
      melanoma cells increases their haptotactic migration on extracellular matrix
      components. The association was demonstrated by co-immunoprecipitation,
      reimmunoprecipitation, and immunoblotting of surface-labeled cells lysed in Brij
      96 detergent. Confocal microscopy illustrated the co-association of alpha(3) and
      CD36 in cell membrane projections and ruffles. A requirement for the
      extracellular domain of CD36 in this association was shown by co
      immunoprecipitation experiments using surface-labeled MV3 melanoma or COS-7 cells
      that had been transiently transfected with chimeric constructs between CD36 and
      intercellular adhesion molecule 1 (ICAM-1) or with a truncation mutant of CD36.
      CD36 is known to engage in signal transduction and to localize to membrane
      microdomains or rafts in several cell types. Toward a mechanistic explanation for
      the functional effects of CD36 expression, we demonstrate that in fractionated
      Triton X-100 lysates of the MV3 cells stably transfected with CD36, CD36 was
      greatly enriched with the detergent-insoluble fractions that represent plasma
      membrane rafts. Significantly, when these fractionated lysates were reprobed for
      endogenous beta(1) integrin, it was found that a 4-fold increase in the
      proportion of the mature protein was contained within the detergent-insoluble
      fractions when extracted from the CD36-transfected cells compared with MV3 cells
      transfected with vector only. These results suggest that in melanoma cells CD36
      expression may induce the sequestration of certain integrins into membrane
      microdomains and promote cell migration.

PMID- 10956646
TI  - Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity
      receptor for TNF family members APRIL and BLyS.
AB  - An expression cloning approach was employed to identify the receptor for B
      lymphocyte stimulator (BLyS) and identified the tumor necrosis factor receptor
      superfamily member TACI as a BLyS-binding protein. Expression of TACI in HEK293T
      cells confers on the cells the ability to bind BLyS with subnanomolar affinity.
      Furthermore, a TACI-Fc fusion protein recognizes both the cleaved, soluble form
      of BLyS as well as the membrane BLyS present on the cell surface of a recombinant
      cell line. TACI mRNA is found predominantly in B-cells and correlates with BLyS
      binding in a panel of B-cell lines. We also demonstrate that TACI interacts with
      nanomolar affinity with the BLyS-related tumor necrosis factor homologue APRIL
      for which no clear in vivo role has been described. BLyS and APRIL are capable of
      signaling through TACI to mediate NF-kappaB responses in HEK293 cells. We
      conclude that TACI is a receptor for BLyS and APRIL and discuss the implications
      for B-cell biology.

PMID- 10956648
TI  - Structural determination of lipid-bound ApoA-I using fluorescence resonance
      energy transfer.
AB  - Based on the x-ray crystal structure of lipid-free Delta43 apoA-I, two monomers
      of apoA-I were suggested to bind to a phospholipid bilayer in an antiparallel
      paired dimer, or "belt orientation." This hypothesis challenges the currently
      held model in which each of the two apoA-I monomers fold as antiparallel alpha
      helices or "picket fence orientation." When apoA-I is bound to a phospholipid
      disc, the first model predicts that the glutamine at position 132 on one apoA-I
      molecule lies within 16 A of glutamine 132 in the second monomer, whereas, the
      second model predicts glutamines at position 132 to be 104 A apart. To
      distinguish between these models, glutamine at position 132 was mutated to
      cysteine in wild-type apoA-I to produce Q132C apoA-I, which were labeled with
      thiol-reactive fluorescent probes. Q132C apoA-I was labeled with either
      fluorescein (donor probe) or tetramethylrhodamine (acceptor probe) and then used
      to make recombinant phospholipid discs (recombinant high density lipoprotein
      (rHDL)). The rHDL containing donor- and acceptor-labeled Q132C apoA-I were of
      similar size, composition, and lecithin:cholesterol acyltransferase reactivity
      when compared to rHDL-containing human plasma apoA-I. Analysis of donor probe
      fluorescence showed highly efficient quenching in rHDL containing one donor- and
      one acceptor-labeled Q132C apoA-I. rHDL containing only acceptor probe-labeled
      Q132C apoA-I showed rhodamine self-quenching. Both of these observations
      demonstrate that position 132 in two lipid-bound apoA-I monomers were in close
      proximity, supporting the "belt conformation" hypothesis for apoA-I on rHDL.

PMID- 10956649
TI  - A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's
      beta -secretase.
AB  - The novel transmembrane aspartic protease BACE (for Beta-site APP Cleaving
      Enzyme) is the beta-secretase that cleaves amyloid precursor protein to initiate
      beta-amyloid formation. As such, BACE is a prime therapeutic target for the
      treatment of Alzheimer's disease. BACE, like other aspartic proteases, has a
      propeptide domain that is removed to form the mature enzyme. BACE propeptide
      cleavage occurs at the sequence RLPR downward arrowE, a potential furin
      recognition motif. Here, we explore the role of furin in BACE propeptide domain
      processing. BACE propeptide cleavage in cells does not appear to be
      autocatalytic, since an inactive D93A mutant of BACE is still cleaved
      appropriately. BACE and furin co-localize within the Golgi apparatus, and
      propeptide cleavage is inhibited by brefeldin A and monensin, drugs that disrupt
      trafficking through the Golgi. Treatment of cells with the calcium ionophore,
      leading to inhibition of calcium-dependent proteases including furin, or
      transfection with the alpha(1)-antitrypsin variant alpha(1)-PDX, a potent furin
      inhibitor, dramatically reduces cleavage of the BACE propeptide. Moreover, the
      BACE propeptide is not processed in the furin-deficient LoVo cell line; however,
      processing is restored upon furin transfection. Finally, in vitro digestion of
      recombinant soluble BACE with recombinant furin results in complete cleavage only
      at the established E46 site. Taken together, our results strongly suggest that
      furin, or a furin-like proprotein convertase, is responsible for cleaving the
      BACE propeptide domain to form the mature enzyme.

PMID- 10956650
TI  - The roles of annexins and types II and X collagen in matrix vesicle-mediated
      mineralization of growth plate cartilage.
AB  - Annexins II, V, and VI are major components of matrix vesicles (MV), i.e.
      particles that have the critical role of initiating the mineralization process in
      skeletal tissues. Furthermore, types II and X collagen are associated with MV,
      and these interactions mediated by annexin V stimulate Ca(2+) uptake and
      mineralization of MV. However, the exact roles of annexin II, V, and VI and the
      interaction between annexin V and types II and X collagen in MV function and
      initiation of mineralization are not well understood. In this study, we
      demonstrate that annexin II, V, or VI mediate Ca(2+) influx into
      phosphatidylserine (PS)-enriched liposomes, liposomes containing lipids extracted
      from authentic MV, and intact authentic MV. The annexin Ca(2+) channel blocker, K
      201, not only inhibited Ca(2+) influx into fura-2-loaded PS-enriched liposomes
      mediated by annexin II, V, or VI, but also inhibited Ca(2+) uptake by authentic
      MV. Types II and X collagen only bound to liposomes in the presence of annexin V
      but not in the presence of annexin II or VI. Binding of these collagens to
      annexin V stimulated its Ca(2+) channel activities, leading to an increased
      Ca(2+) influx into the liposomes. These findings indicate that the formation of
      annexin II, V, and VI Ca(2+) channels in MV together with stimulation of annexin
      V channel activity by collagen (types II and X) binding can explain how MV are
      able to rapidly take up Ca(2+) and initiate the formation of the first crystal
      phase.

PMID- 10956651
TI  - Cold adaptation of microtubule assembly and dynamics. Structural interpretation
      of primary sequence changes present in the alpha- and beta-tubulins of Antarctic
      fishes.
AB  - The microtubules of Antarctic fishes, unlike those of homeotherms, assemble at
      very low temperatures (-1.8 degrees C). The adaptations that enhance assembly of
      these microtubules are intrinsic to the tubulin dimer and reduce its critical
      concentration for polymerization at 0 degrees C to approximately 0.9 mg/ml
      (Williams, R. C., Jr., Correia, J. J., and DeVries, A. L. (1985) Biochemistry 24,
      2790-2798). Here we demonstrate that microtubules formed by pure brain tubulins
      of Antarctic fishes exhibit slow dynamics at both low (5 degrees C) and high (25
      degrees C) temperatures; the rates of polymer growth and shortening and the
      frequencies of interconversion between these states are small relative to those
      observed for mammalian microtubules (37 degrees C). To investigate the
      contribution of tubulin primary sequence variation to the functional properties
      of the microtubules of Antarctic fishes, we have sequenced brain cDNAs that
      encode 9 alpha-tubulins and 4 beta-tubulins from the yellowbelly rockcod
      Notothenia coriiceps and 4 alpha-tubulins and 2 beta-tubulins from the ocellated
      icefish Chionodraco rastrospinosus. The tubulins of these fishes were found to
      contain small sets of unique or rare residue substitutions that mapped to the
      lateral, interprotofilament surfaces or to the interiors of the alpha- and beta
      polypeptides; longitudinal interaction surfaces are not altered in the fish
      tubulins. Four changes (A278T and S287T in alpha; S280G and A285S in beta) were
      present in the S7-H9 interprotofilament "M" loops of some monomers and would be
      expected to increase the flexibility of these regions. A fifth lateral
      substitution specific to the alpha-chain (M302L or M302F) may increase the
      hydrophobicity of the interprotofilament interaction. Two hydrophobic
      substitutions (alpha:S187A in helix H5 and beta:Y202F in sheet S6) may act to
      stabilize the monomers in conformations favorable to polymerization. We propose
      that cold adaptation of microtubule assembly in Antarctic fishes has occurred in
      part by evolutionary restructuring of the lateral surfaces and the cores of the
      tubulin monomers.

PMID- 10956652
TI  - The relaxin receptor-binding site geometry suggests a novel gripping mode of
      interaction.
AB  - Relaxin has a unique, clearly identifiable, mixed function receptor-binding
      region comprising amino acid residues that evolve sequentially from the central
      portion of the B chain alpha-helix. Two arginine residues in positions B13 and
      B17 that project like forefinger and middle finger from the helix provide the
      electrostatic element opposed by the hydrophobic (thumb) element isoleucine
      (B20), offset from the arginines by about 40 degrees. The binding intensity of
      relaxin to its receptor decreases by 3 orders of magnitude if alanine is
      substituted for the newly discovered binding component isoleucine in position
      B20. The arginine residues cannot be replaced by other positive charges, nor can
      the guanidinium group be presented on a longer or shorter hydrocarbon chain. In
      contrast, the hydrophobic interaction is incremental in nature, and the
      contribution to the total binding energy is roughly proportional to the number of
      hydrocarbon units in the side chain. It appears that a hydrophobic surface exists
      on the receptor that offers optimal van der Waals' interaction with beta-branched
      hydrophobic amino acids. The binding energy increases roughly 10-fold with each
      methylene group whereby beta-branching is more effective per surface unit than
      chain elongation. Aromatic side chains appear to demarcate the extent of the
      binding region in so far as residues larger than phenylalanine decrease receptor
      binding. The exceptional clarity of binding site geometry in relaxin makes for an
      excellent opportunity to design peptido-mimetics.

PMID- 10956653
TI  - Studies with substrate and cofactor analogues provide evidence for a radical
      mechanism in the chorismate synthase reaction.
AB  - Chorismate synthase catalyzes the conversion of 5-enolpyruvylshikimate 3
      phosphate (EPSP) to chorismate. The strict requirement for a reduced FMN cofactor
      and a trans-1,4-elimination are unusual. (6R)-6-Fluoro-EPSP was shown to be
      converted to chorismate stoichiometrically with enzyme-active sites in the
      presence of dithionite. This conversion was associated with the oxidation of FMN
      to give a stable flavin semiquinone. The IC(50) of the fluorinated substrate
      analogue was 0.5 and 250 microm with the Escherichia coli enzyme, depending on
      whether it was preincubated with the enzyme or not. The lack of dissociation of
      the flavin semiquinone and chorismate from the enzyme appears to be the basis of
      the essentially irreversible inhibition by this analogue. A dithionite-dependent
      transient formation of flavin semiquinone during turnover of (6S)-6-fluoro-EPSP
      has been observed. These reactions are best rationalized by radical chemistry
      that is strongly supportive of a radical mechanism occurring during normal
      turnover. The lack of activity with 5-deaza-FMN provides additional evidence for
      the role of flavin in catalysis by the E. coli enzyme.

PMID- 10956654
TI  - An A245T mutation conveys on cytochrome P450eryF the ability to oxidize
      alternative substrates.
AB  - Cytochrome P450(eryF) (CYP107A1), which hydroxylates deoxyerythronolide B in
      erythromycin biosynthesis, lacks the otherwise highly conserved threonine that is
      thought to promote O-O bond scission. The role of this threonine is satisfied in
      P450(eryF) by a substrate hydroxyl group, making deoxyerythronolide B the only
      acceptable substrate. As shown here, replacement of Ala(245) by a threonine
      enables the oxidation of alternative substrates using either H(2)O(2) or
      O(2)/spinach ferredoxin/ferredoxin reductase as the source of oxidizing
      equivalents. Testosterone is oxidized to 1-, 11alpha-, 12-, and 16alpha
      hydroxytestosterone. A kinetic solvent isotope effect of 2.2 indicates that the
      A245T mutation facilitates dioxygen bond cleavage. This gain-of-function evidence
      confirms the role of the conserved threonine in P450 catalysis. Furthermore, a
      Hill coefficient of 1.3 and dependence of the product distribution on the
      testosterone concentration suggest that two testosterone molecules bind in the
      active site, in accord with a published structure of the P450(eryF)
      androstenedione complex. P450(eryF) is thus a structurally defined model for the
      catalytic turnover of multiply bound substrates proposed to occur with CYP3A4. In
      view of its large active site and defined structure, catalytically active
      P450(eryF) mutants are also attractive templates for the engineering of novel
      P450 activities.

PMID- 10956655
TI  - Detergent-resistant microdomains offer no refuge for proteins phosphorylated by
      the IgE receptor.
AB  - When the high affinity receptor for IgE and related receptors become aggregated,
      they emigrate to specialized microdomains of the plasma membrane that are
      enriched in certain lipids and lipid-anchored proteins. Among the latter are the
      kinases that initiate signaling cascade(s) by phosphorylating the receptors. In
      studying the IgE receptor, we explored whether, in addition to their potential
      role in enhancing the initiation of signaling by the kinase(s), the microdomains
      might augment the stimulation by excluding phosphatases. In vitro assessment of
      phosphatase activity, using either a relevant or irrelevant substrate, suggested
      that the microdomains were deficient in phosphatase activity, but, in vivo,
      proteins confined to the microdomains were found to be no less vulnerable to
      dephosphorylation than those outside such domains. In the course of our
      experiments, we observed that the procedures routinely used to isolate the
      detergent-resistant domains dissociated the receptor for IgE, thereby
      artificially accentuating the observed preferential distribution of
      phosphorylated subunits in the microdomains.

PMID- 10956656
TI  - Occurrence of heparin in the invertebrate styela plicata (Tunicata) is restricted
      to cell layers facing the outside environment. An ancient role in defense?
AB  - Heparin is an intracellular product of vertebrate mast cell currently used as
      exogenous anticoagulant. Despite of the potent biological activities of exogenous
      heparin, its physiological function has not been clearly established yet. Here, a
      heparin with similar structure and anticoagulant properties to the mammalian
      counterpart was shown to occur as the intracellular product of test cells, a cell
      monolayer that surrounds egg of the invertebrate Styela plicata (Chordata
      Tunicata). As in the case of mammalian mast cells, heparin from the ascidian test
      cells is removed from the intracellular granules after incubation with compound
      48/80. Following fertilization, the test cells surrounding the developing larva
      still retain heparin as metachromatic granulation. In the adult invertebrate,
      heparin occurs as intracellular granules at the apical tip of epithelial cells
      surrounding the lumen of both intestine and pharynx, in close contact with the
      external environment. This is the first description of the presence of heparin in
      cytoplasmic granules of epithelial-like cells around the lumen of sites exposed
      to external agents. This arrangement may reflect the participation of heparin in
      defense mechanisms in this invertebrate.

PMID- 10956657
TI  - Characterization of hydra type IV collagen. Type IV collagen is essential for
      head regeneration and its expression is up-regulated upon exposure to glucose.
AB  - Hydra vulgaris mesoglea is a primitive basement membrane that also exhibits some
      features of an interstitial matrix. We have characterized cDNAs that encode the
      full-length hydra alpha1(IV) chain. The 5169-base pair transcript encodes a
      protein of 1723 amino acids, including an interrupted 1455-residue collagenous
      domain and a 228-residue C-terminal noncollagenous domain. N-terminal sequence
      analyses of collagen IV peptides suggest the molecule is homotrimeric. Denatured
      hydra type IV collagen protein occurs as dimers and higher order aggregates held
      together by nonreducible cross-links. Hydra collagen IV exhibits no functional
      evidence for the presence of a 7 S domain. Type IV collagen is expressed by the
      ectoderm along the entire longitudinal axis of the animal but is most intense at
      the base of the tentacles at the site of battery cell transdifferentiation.
      Antisense studies show that inhibition of collagen IV translation causes a
      blockage in head regeneration, indicating its importance in normal hydra
      development. Exposure of adult hydra to 15 mm glucose resulted in up-regulation
      of type IV collagen mRNA levels within 48 h and significant thickening of the
      mesoglea within 14 days, suggesting that basement membrane thickening seen in
      diabetes may be, in evolutionary terms, an ancient glucose-mediated response.

PMID- 10956658
TI  - Induction of positive cooperativity by amino acid replacements within the C
      terminal domain of Penicillium chrysogenum ATP sulfurylase.
AB  - ATP sulfurylase from Penicillium chrysogenum is an allosteric enzyme in which Cys
      509 is critical for maintaining the R state. Cys-509 is located in a C-terminal
      domain that is 42% identical to the conserved core of adenosine 5'-phosphosulfate
      (adenylylsulfate) (APS) kinase. This domain is believed to provide the binding
      site for the allosteric effector, 3'-phosphoadenosine 5'-phosphosulfate (PAPS).
      Replacement of Cys-509 with either Tyr or Ser destabilizes the R state, resulting
      in an enzyme that is intrinsically cooperative at pH 8 in the absence of PAPS.
      The kinetics of C509Y resemble those of the wild type enzyme in which Cys-509 has
      been covalently modified. The kinetics of C509S resemble those of the wild type
      enzyme in the presence of PAPS. It is likely that the negative charge on the Cys
      509 side chain helps to stabilize the R state. Treatment of the enzyme with a low
      level of trypsin results in cleavage at Lys-527, a residue that lies in a region
      analogous to a PAPS motif-containing mobile loop of true APS kinase. Both mutant
      enzymes were cleaved more rapidly than the wild type enzyme, suggesting that
      movement of the mobile loop occurs during the R to T transition.

PMID- 10956659
TI  - Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal
      structure of its enzyme-substrate analog complex.
AB  - The serine protease thrombin proteolytically activates blood coagulation factor
      XIII by cleavage at residue Arg(37); factor XIII in turn cross-links fibrin
      molecules and gives mechanical stability to the blood clot. The 2.0-A resolution
      x-ray crystal structure of human alpha-thrombin bound to the factor XIII-(28-37)
      decapeptide has been determined. This structure reveals the detailed atomic level
      interactions between the factor XIII activation peptide and thrombin and provides
      the first high resolution view of this functionally important part of the factor
      XIII molecule. A comparison of this structure with the crystal structure of
      fibrinopeptide A complexed with thrombin highlights several important
      determinants of thrombin substrate interaction. First, the P1 and P2 residues
      must be compatible with the geometry and chemistry of the S1 and S2 specificity
      sites in thrombin. Second, a glycine in the P5 position is necessary for the
      conserved substrate conformation seen in both factor XIII-(28-37) and
      fibrinopeptide A. Finally, the hydrophobic residues, which occupy the aryl
      binding site of thrombin determine the substrate conformation further away from
      the catalytic residues. In the case of factor XIII-(28-37), the aryl binding site
      is shared by hydrophobic residues P4 (Val(34)) and P9 (Val(29)). A bulkier
      residue in either of these sites may alter the substrate peptide conformation.

PMID- 10956660
TI  - Identification of repair enzymes for 5-formyluracil in DNA. Nth, Nei, and MutM
      proteins of Escherichia coli.
AB  - 5-Formyluracil (5-foU) is a potentially mutagenic lesion of thymine produced in
      DNA by ionizing radiation and various chemical oxidants. Although 5-foU has been
      reported to be removed from DNA by Escherichia coli AlkA protein in vitro, its
      repair mechanisms are not fully understood. In this study, we used the
      borohydride trapping assay to detect and characterize repair activities for 5-foU
      in E. coli extracts with site-specifically designed oligonucleotides containing a
      5-foU at defined sites. The trapping assay revealed that there are three kinds of
      proteins that form covalent complexes with the 5-foU-containing oligonucleotides.
      Extracts from strains defective in the nth, nei, or mutM gene lacked one of the
      proteins. All of the trapped complexes were completely lost in extracts from the
      nth nei mutM triple mutant. The introduction of a plasmid carrying the nth, nei,
      or mutM gene into the E. coli triple mutant restored the formation of the
      corresponding protein-DNA complex. Purified Nth, Nei, and MutM proteins were
      trapped by the 5-foU-containing oligonucleotide to form the complex in the
      presence of NaBH(4). Furthermore, the purified Nth, Nei, and MutM proteins
      efficiently cleaved the oligonucleotide at the 5-foU site. In addition, 5-foU was
      site-specifically incorporated into plasmid pSVK3, and the resulting plasmid was
      replicated in E. coli. The mutation frequency of the plasmid was significantly
      increased in the E. coli nth nei mutM alkA mutant, compared with the wild-type
      and alkA strains. From these results it is concluded that the Nth, Nei, and MutM
      proteins are involved in the repair pathways for 5-foU that serve to avoid
      mutations in E. coli.

PMID- 10956661
TI  - Sulfation of N-acetylglucosamine by chondroitin 6-sulfotransferase 2 (GST-5).
AB  - Based on sequence homology with a previously cloned human GlcNAc 6-O
      sulfotransferase, we have identified an open reading frame (ORF) encoding a novel
      member of the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family termed GST-5 on
      the human X chromosome (band Xp11). GST-5 has recently been characterized as a
      novel GalNAc 6-O-sulfotransferase termed chondroitin 6-sulfotransferase-2
      (Kitagawa, H., Fujita, M., Itio, N., and Sugahara K. (2000) J. Biol. Chem. 275,
      21075-21080). We have coexpressed a human GST-5 cDNA with a GlyCAM-1/IgG fusion
      protein in COS-7 cells and observed four-fold enhanced [(35)S]sulfate
      incorporation into this mucin acceptor. All mucin-associated [(35)S]sulfate was
      incorporated as GlcNAc-6-sulfate or Galbeta1-->4GlcNAc-6-sulfate. GST-5 was also
      expressed in soluble epitope-tagged form and found to catalyze 6-O-sulfation of
      GlcNAc residues in synthetic acceptor structures. In particular, GST-5 was found
      to catalyze 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl
      GalNAc. In the mouse genome we have found a homologous ORF that predicts a novel
      murine GlcNAc 6-O-sulfotransferase with 88% identity to the human enzyme. This
      gene was mapped to mouse chromosome X at band XA3.1-3.2. GST-5 is the newest
      member of an emerging family of carbohydrate 6-O-sulfotransferases that includes
      chondroitin 6-sulfotransferase (GST-0), keratan-sulfate galactose 6-O
      sulfotransferase (GST-1), the ubiquitously expressed GlcNAc 6-O-sulfotransferase
      (GST-2), high endothelial cell GlcNAc 6-O-sulfotransferase (GST-3), and
      intestinal GlcNAc 6-O-sulfotransferase (GST-4).

PMID- 10956662
TI  - Residues and mechanisms for slow activation and Ba2+ block of the cardiac
      muscarinic K+ channel, Kir3.1/Kir3.4.
AB  - Mechanisms and residues responsible for slow activation and Ba(2+) block of the
      cardiac muscarinic K(+) channel, Kir3.1/Kir3.4, were investigated using site
      directed mutagenesis. Mutagenesis of negatively charged residues located
      throughout the pore of the channel (in H5, M2, and proximal C terminus) reduced
      or abolished slow activation. The strongest effects resulted from mutagenesis of
      residues in H5 close to the selectivity filter; mutagenesis of residues in M2 and
      proximal C terminus equivalent to those identified as important determinants of
      the activation kinetics of Kir2.1 was less effective. In giant patches, slow
      activation was present in cell-attached patches, lost on excision of the patch,
      and restored on perfusion with polyamine. Mutagenesis of residues in H5 and M2
      close to the selectivity filter also decreased Ba(2+) block of the channel. A
      critical residue for Ba(2+) block was identified in Kir3.4. Mutagenesis of the
      equivalent residue in Kir3.1 failed to have as pronounced an effect on Ba(2+)
      block, suggesting an asymmetry of the channel pore. It is concluded that slow
      activation is principally the result of unbinding of polyamines from negatively
      charged residues close to the selectivity filter of the channel and not an
      intrinsic gating mechanism. Ba(2+) block involves an interaction with the same
      residues.

PMID- 10956663
TI  - Spatial regulation and activity modulation of plasmin by high affinity binding to
      the G domain of the alpha 3 subunit of laminin-5.
AB  - Cells in complex tissues contact extracellular matrix that interacts with
      integrin receptors to influence gene expression, proliferation, apoptosis,
      adhesion, and motility. During development, tissue remodeling, and tumorigenesis,
      matrix components are modified by enzymatic digestion with subsequent effects on
      integrin binding and signaling. We are interested in understanding the mechanisms
      by which broad spectrum proteinases such as plasmin are targeted to their
      extracellular matrix protein substrates. We have utilized plasmin-mediated
      cleavage of the epithelial basement membrane glycoprotein laminin-5 as a model to
      evaluate molecular events that direct plasmin activity to specific structural
      domains. We report that plasminogen and tissue plasminogen activator (tPA)
      exhibit high affinity, specific binding to the G(1) subdomain of the N terminus
      of the laminin-5 alpha(3) subunit, with equilibrium dissociation constants of 50
      nm for plasminogen and 80 nm for tPA. No high affinity binding to the G(2), G(3),
      and G(4) subdomains was observed. As a result of binding to the G(1) subdomain,
      the catalytic efficiency of tPA-catalyzed plasminogen activation is enhanced 32
      fold, leading to increased matrix-associated plasmin that is positioned favorably
      for cleavage within the G(4) subdomain as we have reported previously
      (Goldfinger, L. E., Stack, M. S., and Jones, J. C. R. (1998) J. Cell Biol. 141,
      255-265). Thus, physical constraints dictated by interaction of proteinase and
      matrix macromolecule control not only enzymatic activity but may regulate
      substrate targeting of proteinases.

PMID- 10956664
TI  - The second naphthol reductase of fungal melanin biosynthesis in Magnaporthe
      grisea: tetrahydroxynaphthalene reductase.
AB  - Mutants of Magnaporthe grisea harboring a defective gene for 1,3, 8
      trihydroxynaphthalene reductase retain the capability to produce scytalone, thus
      suggesting the existence of a second naphthol reductase that can catalyze the
      reduction of 1,3,6, 8-tetrahydroxynaphthalene to scytalone within the fungal
      melanin biosynthetic pathway. The second naphthol reductase gene was cloned from
      M. grisea by identification of cDNA fragments with weak homology to the cDNA of
      trihydroxynaphthalene reductase. The amino acid sequence for the second naphthol
      reductase is 46% identical to that of trihydroxynaphthalene reductase. The second
      naphthol reductase was produced in Esherichia coli and purified to homogeneity.
      Substrate competition experiments indicate that the second reductase prefers
      tetrahydroxynaphthalene over trihydroxynaphthalene by a factor of 310;
      trihydroxynaphthalene reductase prefers trihydroxynaphthalene over
      tetrahydroxynaphthalene by a factor of 4.2. On the basis of the 1300-fold
      difference in substrate specificities between the two reductases, the second
      reductase is designated tetrahydroxynaphthalene reductase.
      Tetrahydroxynaphthalene reductase has a 200-fold larger K(i) for the fungicide
      tricyclazole than that of trihydroxynaphthalene reductase, and this accounts for
      the latter enzyme being the primary physiological target of the fungicide. M.
      grisea mutants lacking activities for both trihydroxynaphthalene and
      tetrahydroxynaphthalene reductases do not produce scytalone, indicating that
      there are no other metabolic routes to scytalone.

PMID- 10956665
TI  - Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph
      missing the catalytic domain share exons with junctin.
AB  - The mouse aspartyl beta-hydroxylase gene (Asph, BAH) has been cloned and
      characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and
      contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629
      and 4,419 base pairs) encode full-length protein and differ only in the use of
      alternative polyadenylation signals. The smallest BAH-related transcript (2,789
      base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking
      a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH
      (humbug) is demonstrated in mouse, man, and Drosophila. Monoclonal antibody
      reagents were generated, epitope-mapped, and used to definitively correlate RNA
      bands on Northern blots with protein species on Western blots. The gene for mouse
      junctin, a calsequestrin-binding protein, was cloned and characterized and shown
      to be encoded from the same locus. When expressed in heart tissue, BAH/humbug
      preferably use the first exon and often the fourth exon of junctin while
      preserving the reading frame. Thus, three individual genes share common exons and
      open reading frames and use separate promoters to achieve differential
      expression, splicing, and function in a variety of tissues. This unusual form of
      exon sharing suggests that the functions of junctin, BAH, and humbug may be
      linked.

PMID- 10956667
TI  - Functional and biochemical evidence for G-protein-gated inwardly rectifying K+
      (GIRK) channels composed of GIRK2 and GIRK3.
AB  - G-protein-gated inwardly rectifying K(+) (GIRK) channels are widely expressed in
      the brain and are activated by at least eight different neurotransmitters. As
      K(+) channels, they drive the transmembrane potential toward E(K) when open and
      thus dampen neuronal excitability. There are four mammalian GIRK subunits (GIRK1
      4 or Kir 3.1-4), with GIRK1 being the most unique of the four by possessing a
      long carboxyl-terminal tail. Early studies suggested that GIRK1 was an integral
      component of native GIRK channels. However, more recent data indicate that native
      channels can be either homo- or heterotetrameric complexes composed of several
      GIRK subunit combinations. The functional implications of subunit composition are
      poorly understood at present. The purpose of this study was to examine the
      functional and biochemical properties of GIRK channels formed by the co-assembly
      of GIRK2 and GIRK3, the most abundant GIRK subunits found in the mammalian brain.
      To examine the properties of a channel composed of these two subunits, we co
      transfected GIRK2 and GIRK3 in CHO-K1 cells and assayed the cells for channel
      activity by patch clamp. The most significant difference between the putative
      GIRK2/GIRK3 heteromultimeric channel and GIRK1/GIRKx channels at the single
      channel level was an approximately 5-fold lower sensitivity to activation by
      Gbetagamma. Complexes containing only GIRK2 and GIRK3 could be immunoprecipitated
      from transfected cells and could be purified from native brain tissue. These data
      indicate that functional GIRK channels composed of GIRK2 and GIRK3 subunits exist
      in brain.

PMID- 10956666
TI  - Rad22 protein, a rad52 homologue in Schizosaccharomyces pombe, binds to DNA
      double-strand breaks.
AB  - DNA double-strand breaks can be introduced by exogenous agents or during normal
      cellular processes. Genes belonging to the RAD52 epistasis group are known to
      repair these breaks in budding yeast. Among these genes, RAD52 plays a central
      role in homologous recombination and DNA double-strand break repair. Despite its
      importance, its mechanism of action is not yet clear. It is known, however, that
      the human homologue of Rad52 is capable of binding to DNA ends in vitro. Herein,
      we show that Rad22 protein, a Rad52 homologue in the fission yeast
      Schizosaccharomyces pombe, can similarly bind to DNA ends at double-strand
      breaks. This end-binding ability was demonstrated in vitro by electron microscopy
      and by protection from exonuclease attack. We also showed that Rad22 specifically
      binds near double-strand break associated with mating type switching in vivo by
      chromatin immunoprecipitation analysis. This is the first evidence that a
      recombinational protein directly binds to DNA double-strand breaks in vivo.

PMID- 10956668
TI  - Thrombospondin-4 binds specifically to both collagenous and non-collagenous
      extracellular matrix proteins via its C-terminal domains.
AB  - Full-length and truncated forms of rat thrombospondin-4 (TSP-4) were expressed
      recombinantly in a mammalian cell line and purified to homogeneity. Biochemical
      analysis revealed a limited proteolytic processing, which detaches the N-terminal
      heparin-binding domain from the rest of the molecule and confirmed the importance
      of the heptad-repeat domain for pentamerization. In electron microscopy the
      uncleaved TSP-4 was seen as a large central particle to which five smaller
      globules are attached by elongated linker regions. Binding of TSP-4 to collagens
      and to non-collagenous proteins could be detected in enzyme-linked immunosorbent
      assay-style ligand binding assays, by surface plasmon resonance spectroscopy, and
      in rotary shadowing electron microscopy. Although the binding of TSP-4 to solid
      phase collagens was enhanced by Zn(2+), that to non-collagenous proteins was not.
      The interactions of TSP-4 with both classes of proteins are mediated by C
      terminal domains of the TSP-4 subunits but do not require an oligomeric
      structure. Major binding sites for TSP-4 are located in or close to the N- and C
      terminal telopeptides in collagen I, but additional sites are detected in more
      central regions of the molecule.

PMID- 10956669
TI  - The sequential mechanism of HIV reverse transcriptase RNase H.
AB  - Synthesis of the minus strand of viral DNA by human immunodeficiency virus, type
      1 (HIV-1) reverse transcriptase is accompanied by RNase H degradation of the
      viral RNA genome. RNA fragments remain after synthesis and are degraded by the
      polymerase-independent mode of RNase H cleavage. Recently, we showed that this
      mode of cleavage occurs by a specific ordered mechanism in which primary cuts are
      first, secondary and 5-nucleotide cuts are next, and second primary cuts occur
      last (Wisniewski, M., Balakrishnan, M., Palaniappan, C., Fay, P., J., and
      Bambara, R., A. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 11978-11983). Ultimately
      the RNAs are cleaved into small fragments that can dissociate from the DNA
      template. Because the cleavage mechanism is an ordered series of events, we
      determined in this study whether any earlier cut is required for a later cut. By
      precisely inhibiting cleavage at each site, we examined the dependence of later
      cuts on cleavage at that site. We found that each cut is independent of the other
      cuts, demonstrating that the order of this stepwise mechanism is based on the
      rates of each cut. A mechanism for unlinked ordered cleavage consistent with
      these results is presented.

PMID- 10957007
TI  - Internet-based decision-support server for acute abdominal pain.
AB  - The paper describes conception and prototypical design of a decision-support
      server for acute abdominal pain. Existing formal methods to develop and exchange
      scores, guidelines and algorithms are used for integration. For scoring systems a
      work-up to separate terminological information from structure is described. The
      terminology is separately stored in a data dictionary and the structure in a
      knowledge base. This procedure enables a reuse of terminology for documentation
      and decision-support. The whole system covers a decision-support server written
      in C++ with underlying data dictionary and knowledge base, a documentation module
      written in Java and a CORBA middleware that establishes a connection via
      Internet.

PMID- 10957577
TI  - Susceptibility of 1100 Streptococcus pneumoniae strains isolated in 1997 from
      seven Latin American and Caribbean countries. Laser Study Group.
AB  - The antimicrobial susceptibility to beta-lactam and non-beta-lactam agents of
      1100 isolates of Streptococcus pneumoniae recovered in 1997 from 16 centres in
      Argentina, Brazil, Chile, Mexico, Panama, Venezuela and West Indies was studied
      using E-test and disk diffusion methods. A total of 23.6% of isolates had raised
      penicillin MICs (16.7% intermediate and 6.9% resistant). The susceptibility of
      the other agents tested, from most active to least active, were,
      amoxycillin/clavulanate (99.5% susceptible); chloramphenicol (93.2%); cefotaxime
      (91.7%); erythromycin (87.1%); tetracycline (74.6%);
      trimethoprim/sulphamethoxazole (TMP-SMZ) (55.4%); and cefaclor (52.8%). The
      highest proportion of strains resistant to penicillin, chloramphenicol,
      erythromycin, tetracycline and TMP-SMZ was found in strains from Mexico while
      resistance to these agents was lowest in strains from the West Indies. Prevalence
      of penicillin resistance (including intermediate and resistant isolates) in each
      of the countries, from highest to lowest was, Mexico (40.8%); Chile (31.3%);
      Panama (23.0%); Venezuela (21.9%); Argentina (19.1%); Brazil (12.9%); and West
      Indies (7.1%). Based on current levels of antimicrobial resistance of S.
      pneumoniae in Latin American and Caribbean countries, continued surveillance
      efforts are necessary in order to guide clinical empiric treatment and provide
      for judicious use of antimicrobial agents.

PMID- 10956670
TI  - Cell surface expression of calnexin, a molecular chaperone in the endoplasmic
      reticulum.
AB  - The folding and assembly of nascent proteins in the endoplasmic reticulum are
      assisted by the molecular chaperone calnexin, which is itself retained within the
      endoplasmic reticulum. It was up to now assumed that calnexin was selectively
      expressed on the surface of immature thymocytes because of a particular
      characteristic of the protein sorting machinery in these cells. We now report
      that a small fraction of calnexin is normally expressed on the surface of various
      cells such as mastocytoma cells, murine splenocytes, fibroblast cells, and human
      HeLa cells. Surface biotinylation followed by chase culture of living cells
      revealed that calnexin is continuously delivered to the cell surface and then
      internalized for lysosomal degradation. These results suggest that there is
      continuous exocytosis and endocytosis of calnexin, and the amount of calnexin on
      the plasma membrane results from the balance of the rates of these two events. To
      study the structural requirement of calnexin for surface expression, we created
      deletion mutants of calnexin and found that the luminal domain, particularly the
      glycoprotein binding domain, is necessary. These findings suggest that the
      surface expression of calnexin depends on the association with glycoproteins and
      that calnexin may play a certain role as a chaperone on the plasma membrane as
      well.

PMID- 10957579
TI  - Spectrum and transferability of beta-lactam resistance in hospital strains of
      Enterobacter isolated in Bratislava and Innsbruck.
AB  - The transferability and expression of beta-lactam resistance were compared in
      multiresistant clinical isolates of Enterobacter spp. collected from different
      hospitals in Bratislava, Slovakia (n = 15) and Innsbruck, Austria (n = 19) during
      1996-1997. The strains from Bratislava were resistant to ampicillin, cefoxitin,
      cefotaxime, ceftazidime and ceftriaxone. All strains from Innsbruck were
      resistant to ampicillin and cefoxitin; 17 were also resistant to ceftazidime and
      aztreonam but the majority remained susceptible to cefotaxime and ceftriaxone.
      All strains were susceptible to cefepime and imipenem. The majority of the tested
      strains transferred resistance determinants to E. coli recipient by conjugation.
      Production of beta-lactamase including ESBL was the major mechanism of beta
      lactam resistance. Large plasmids of 77-88 and 91 kb were confirmed in clinical
      isolates from Bratislava and Innsbruck.

PMID- 10957627
TI  - Structure of human transthyretin complexed with bromophenols: a new mode of
      binding.
AB  - The binding of two organohalogen substances, pentabromophenol (PBP) and 2,4,6
      tribromophenol (TBP), to human transthyretin (TTR), a thyroid hormone transport
      protein, has been studied by in vitro competitive binding assays and by X-ray
      crystallography. Both compounds bind to TTR with high affinity, in competition
      with the natural ligand thyroxine (T(4)). The crystal structures of the TTR-PBP
      and TTR-TBP complexes show some unusual binding patterns for the ligands. They
      bind exclusively in the 'reversed' mode, with their hydroxyl group pointing
      towards the mouth of the binding channel and in planes approximately
      perpendicular to that adopted by the T(4) phenolic ring in a TTR-T(4) complex, a
      feature not observed before. The hydroxyl group in the ligands, which was
      previously thought to be a key ingredient for a strong binding to TTR, does not
      seem to play an important role in the binding of these compounds to TTR. In the
      TTR-PBP complex, it is primarily the halogens which interact with the TTR
      molecule and therefore must account for the strong affinity of binding. The
      interactions with the halogens are smaller in number in TTR-TBP and there is a
      decrease in affinity, even though the interaction with the hydroxyl group is
      stronger than that in the TTR-PBP complex.

PMID- 10957629
TI  - Structures of feline immunodeficiency virus dUTP pyrophosphatase and its
      nucleotide complexes in three crystal forms.
AB  - dUTP pyrophosphatase (dUTPase) cleaves the alpha-beta phosphodiester of dUTP to
      form pyrophosphate and dUMP, preventing incorporation of uracil into DNA and
      providing the substrate for thymine synthesis. Seven crystal structures of feline
      immunodeficiency virus (FIV) dUTPase in three crystal forms have been determined,
      including complexes with substrate (dUTP), product (dUMP) or inhibitor (dUDP)
      bound. The native enzyme has been refined at 1.40 A resolution in a hexagonal
      crystal form and at 2.3 A resolution in an orthorhombic crystal form. In the dUDP
      complex in a cubic crystal form refined at 2.5 A resolution, the C-terminal
      conserved P-loop motif is fully ordered. The analysis defines the roles of five
      sequence motifs in interaction with uracil, deoxyribose and the alpha-, beta- and
      gamma-phosphates. The enzyme utilizes adaptive recognition to bind the alpha- and
      beta-phosphates. In particular, the alpha-beta phosphodiester adopts an
      unfavorable eclipsed conformation in the presence of the P-loop. This
      conformation may be relevant to the mechanism of alpha-beta phosphodiester bond
      cleavage.

PMID- 10957628
TI  - Structure of jack bean chitinase.
AB  - The structure of jack bean chitinase was solved at 1.8 A resolution by molecular
      replacement. It is an alpha-helical protein with three disulfide bridges. The
      active site is related in structure to animal and viral lysozymes. However,
      unlike in lysozyme, the architecture of the active site suggests a single-step
      cleavage. According to this mechanism, Glu68 is the proton donor and Glu90
      assists in the reaction by moving towards the substrate and recruiting a water
      molecule that acts as the nucleophile. In this model, a water molecule was found
      in contact with Glu90 O(epsilon1) and Thr119 O(gamma) at a distance of 3.0 and
      2.8 A, respectively. The model is in accordance with the observed inversion
      mechanism.

PMID- 10957630
TI  - Hydration, mobility and accessibility of lysozyme: structures of a pH 6.5
      orthorhombic form and its low-humidity variant and a comparative study involving
      20 crystallographically independent molecules.
AB  - The structure analyses of orthorhombic lysozyme grown at pH 6.5 and its low
      humidity variant are reported. The structures of the same form grown at pH 9.5
      and 4.5 and that of the low-humidity variant of the pH 9.5 form are available. A
      comparison between them shows that the changes in molecular geometry and
      hydration caused by changes in the amount of solvent surrounding protein
      molecules are more pronounced than those caused by variation in pH. In
      particular, the conformation and the mutual orientation of the catalytic residues
      Glu35 and Asp52 remain unaffected by change in pH. A comparative study involving
      20 crystallographically independent lysozyme molecules, including five in the
      orthorhombic form, leads to the delineation of the relatively rigid, moderately
      flexible and highly flexible regions of the molecule. Half the binding cleft
      (subsites D, E and F) belong to the rigid region but the other half (subsites A,
      B and C) belong to a flexible region. There is no marked correlation between
      relative rigidity and conservation of side-chain conformation except at the
      binding site. The study permits the identification of seven invariant water
      molecules associated with the protein. Most of them are involved in important
      tertiary interactions, while one occurs in the active-site cleft. The study
      demonstrates a weak correlation between non-accessibility and rigidity. On
      average, the level of hydration of polar atoms increases rapidly with accessible
      atomic surface area, but levels off at about 15 A(2) at a little over one ordered
      water molecule per polar protein atom. Only 15 N and O atoms are hydrated in all
      20 molecules. 13 of these are hydrated by the seven invariant water molecules. Of
      the seven, only one water molecule is totally buried within the protein.

PMID- 10957631
TI  - Use of an N-terminal fragment from moloney murine leukemia virus reverse
      transcriptase to facilitate crystallization and analysis of a pseudo-16-mer DNA
      molecule containing G-A mispairs.
AB  - Complexation with the N-terminal fragment of Moloney murine leukemia virus
      reverse transcriptase offers a novel method of obtaining crystal structures of
      nucleic acid duplexes, which can be phased by molecular replacement. This method
      is somewhat similar to the method of using a monoclonal antibody Fab fragment
      complexed to the molecule of interest in order to obtain crystals suitable for X
      ray crystallographic analysis. Here a novel DNA structure including two G-A
      mispairs in a pseudo-hexadecamer determined at 2.3 A resolution in a complex with
      the N-terminal fragment is reported. This structure has an asymmetric unit
      consisting of the protein molecule bound to the blunt end of a DNA 6/10-mer,
      which is composed of a six-base strand (5'-CTCGTG-3') and a ten-base strand (3'
      GAGCACGGCA-5'). The 6/10-mer is thus composed of a six-base-pair duplex with a
      four-base single-stranded overhang. In the crystal structure, the bases of the
      overhang are reciprocally paired (symmetry element -x - 1, -y, z), yielding a
      doubly nicked pseudo-hexadecamer primarily B-form DNA molecule, which has some
      interesting A-like structural features. The pairing between the single strands
      results in two standard (G-C) Watson-Crick pairs and two G-A mispairs. The
      structural DNA model can accommodate either a standard syn or a standard anti
      conformation for the 5'-terminal adenine of the ten-base strand of the DNA based
      on analysis of simulated-annealing omit maps. Although the DNA model here
      includes nicks in the phosphodiester backbone, modeling of an intact
      phosphodiester backbone results in a very similar DNA model and indicates that
      the structure is biologically relevant.

PMID- 10957632
TI  - A flexible and efficient procedure for the solution and phase refinement of
      protein structures.
AB  - An ab initio method is described for solving protein structures for which atomic
      resolution (better than 1.2 A) data are available. The problem is divided into
      two stages. Firstly, a substructure composed of a small percentage (
      approximately 5%) of the scattering matter of the unit cell is positioned. This
      is used to generate a starting set of phases that are slightly better than
      random. Secondly, the full structure is developed from this phase set. The
      substructure can be a constellation of atoms that scatter anomalously, such as
      metal or S atoms. Alternatively, a structural fragment such as an idealized alpha
      helix or a motif from some distantly related protein can be orientated and
      sometimes positioned by an extensive molecular-replacement search, checking the
      correlation coefficient between observed and calculated structure factors for the
      highest normalized structure-factor amplitudes |E|. The top solutions are further
      ranked on the correlation coefficient for all E values. The phases generated from
      such fragments are improved using Patterson superposition maps and Sayre-equation
      refinement carried out with fast Fourier transforms. Phase refinement is
      completed using a novel density-modification process referred to as dynamic
      density modification (DDM). The method is illustrated by the solution of a number
      of known proteins. It has proved fast and very effective, able in these tests to
      solve proteins of up to 5000 atoms. The resulting electron-density maps show the
      major part of the structures at atomic resolution and can readily be interpreted
      by automated procedures.

PMID- 10957634
TI  - Logos for amino-acid preferences in different backbone packing density regions of
      protein structural classes.
AB  - A protein sequence can be classified into one of four structural classes, namely
      alpha, beta, alpha + beta and alpha/beta, based on its amino-acid composition.
      The present study aims at understanding why a particular sequence with a given
      amino-acid composition should fold into a specific structural class. In order to
      answer this question, each amino acid in the protein sequence was classified to a
      particular neighbor density based on the number of spatial residues surrounding
      it within a distance of 6.5 A. Each of the four structural classes showed a
      unique preference of amino acids in each of the neighbor densities. Residues
      which show a high compositional bias in a structural class are also found to
      occur in high neighbor densities. This high compositional bias towards specific
      residues in the four different structural classes of proteins appears to be
      caused by structural and functional requirements. The distribution of amino acids
      in different neighbor densities is graphically presented in a novel logo form
      which incorporates several features such as composition, the frequency of
      occurrence and color code for amino acids. The spatial neighbors of the residues
      in different neighbor densities and their secondary structural location are also
      represented in the form of logos. This representation helped in the
      identification of specific details of the whole data which may otherwise have
      gone unnoticed. It is suggested that the data presented in this study may be
      useful in knowledge-based structure modelling and de novo protein design.

PMID- 10957633
TI  - Globbic approximation in low-resolution direct-methods phasing.
AB  - Probabilistic direct-methods phasing theory, originally based on a uniform atomic
      distribution hypothesis, is shown to be adaptable to a non-uniform bulk-solvent
      compensated globbic approximation for protein crystals at low resolution. The
      effective number n(g) of non-H protein atoms per polyatomic glob increases with
      decreasing resolution; low-resolution phases depend on the positions of only N(g)
      = N(a)/n(g) globs rather than N(a) atoms. Test calculations were performed with
      measured structure-factor data and the refined structural parameters from a
      protein crystal with approximately 10 000 non-H protein atoms per molecule and
      approximately 60% solvent volume. Low-resolution data sets with d(min) ranging
      from 15 to 5 A gave n(g) = ad(min) + b, with a = 1.0 A(-1) and b = -1.9 for the
      test case. Results of tangent-formula phase-estimation trials emphasize that
      completeness of the low-resolution data is critically important for probabilistic
      phasing.

PMID- 10957635
TI  - Crystallization, preliminary X-ray analysis of a native and selenomethionine D
      hydantoinase from Thermus sp.
AB  - A D-hydantoinase from Thermus sp. was expressed in Escherichia coli, purified to
      homogeneity and crystallized both as native and Se-Met labelled protein. The
      crystals belong to the orthorhombic space group C222(1), with unit-cell
      parameters a = 125.9, b = 215.8, c = 207.5 A. A three-wavelength MAD data set was
      collected to 2.5 A resolution and a native data set was collected to 1.7 A
      resolution. Crystal packing and self-rotation calculations led to the assumption
      of six protomers per asymmetric unit, corresponding to a V(M) value of 2.28 A(3)
      Da(-1) and a solvent content of 46%. As each protomer contains nine Se-Met
      residues, 54 selenium sites per asymmetric unit were present and could be
      unambigously located in the course of the MAD experiment. This selenium
      substructure is one of the largest selenium substructures that have been solved
      to date. The resulting phases obtained at a high-resolution limit of 3.0 A could
      be extended to 1.7 A and refined by application of density-modification
      techniques, especially non-crystallographic symmetry.

PMID- 10957636
TI  - Crystallization of the dI component of transhydrogenase, a proton-translocating
      membrane protein.
AB  - Nicotinamide nucleotide transhydrogenase couples the exchange of a hydride-ion
      equivalent between NAD(H) and NADP(H) to the translocation of protons across an
      energy-transducing membrane. Peripheral components of 380 and 200 residues bind
      NAD(H) (dI) and NADP(H) (dIII), respectively, while a third component forms a
      membrane-spanning region (dII). The NAD(H)-binding component dI of Rhodospirillum
      rubrum transhydrogenase has been crystallized in a form which diffracts to beyond
      3.0 A resolution and is in space group P2 or P2(1), with unit-cell parameters a =
      69.3, b = 117.8, c = 106.6 A, beta = 107.2 degrees and two dimers in the
      asymmetric unit. The sequence of the dI component is similar to that of alanine
      dehydrogenase. A full structure determination will lead to important information
      on the mode of action of this proton pump and will permit the comparison of the
      structure-function relationships of dI with those of alanine dehydrogenase.

PMID- 10957637
TI  - Crystallization and preliminary X-ray diffraction analysis of a cytochrome P450
      (CYP119) from Sulfolobus solfataricus.
AB  - CYP119 is a cytochrome P450 with a molecular weight of 43 kDa which has been
      isolated from the thermophilic archaeon Sulfolobus solfataricus. This enzyme is
      extremely stable to high temperature and high pressure. The first crystallization
      and preliminary crystallographic study of CYP119 is reported here. Crystals of
      CYP119 were obtained by the sitting-drop vapour-diffusion method using a
      precipitant solution containing 20%(w/v) PEG 4000 and 0.2 M sodium thiocyanate at
      pH 6.4. Using synchrotron radiation, the CYP119 crystal diffracted to 1.84 A
      resolution. It belongs to the tetragonal space group P4(3)2(1)2, with unit-cell
      parameters a = b = 86.17 (0.07), c = 221.11 (0.04) A, in which the numbers in
      parentheses describe the standard deviations. Assuming two molecules of the
      CYP119 per asymmetric unit, the calculated molar volume (V(m)) is 2.38 A(3) Da(
      1). Bijvoet and dispersive anomalous difference Patterson maps show a clear peak
      corresponding to the haem irons. The complete crystallographically defined
      structure is currently in progress using MIR (multiple isomorphous replacement)
      and MAD (multiwavelength anomalous diffraction) techniques.

PMID- 10957638
TI  - Cloning, crystallization and preliminary characterization of a beta-carbonic
      anhydrase from Escherichia coli.
AB  - Carbonic anhydrases are zinc metalloenzymes that fall into three distinct
      evolutionary and structural classes, alpha, beta and gamma. Although alpha-class
      enzymes, particularly mammalian carbonic anhydrase II, have been the subject of
      extensive structural studies, for the beta class, consisting of a wide variety of
      prokaryotic and plant chloroplast carbonic anhydrases, the structural data is
      quite limited. A member of the beta class from E. coli (CynT2) has been
      crystallized in native and selenomethionine-labelled forms and multiwavelength
      anomalous dispersion techniques have been applied in order to determine the
      positions of anomalous scatterers. The resulting phase information is sufficient
      to produce an interpretable electron-density map. A crystal structure for CynT2
      would contribute significantly to the emerging structural knowledge of a
      biologically important class of enzymes that perform critical functions in carbon
      fixation and prokaryotic metabolism.

PMID- 10957640
TI  - Crystallization and preliminary crystallographic studies of bar-headed goose
      fluoromethaemoglobin with inositol hexaphosphate.
AB  - Bar-headed goose fluoromethaemoglobin (fluoromet-Hb) complexed with inositol
      hexaphosphate (IHP) has been crystallized using PEG 6000 as precipitant. The
      crystal belongs to space group P2(1), with unit-cell parameters a = 59.8, b =
      72.0, c = 79.8 A, beta = 102.1 degrees, and diffracts to 2.5 A resolution. To
      prove the presence of IHP, the structure was determined by the molecular
      replacement method. IHP was observed at the entrance to the central cavity
      between the N and C termini of two beta subunits.

PMID- 10957639
TI  - Crystallization and preliminary X-ray diffraction analysis of a rat biliverdin
      reductase.
AB  - Biliverdin reductase (BVR) catalyzes the final step of haem degradation and
      converts biliverdin to bilirubin using NAD(P)H as an electron donor. This paper
      deals with the first crystallization and preliminary crystallographic study of
      recombinant rat BVR expressed in Escherichia coli. Crystals of BVR were obtained
      by the sitting-drop vapour-diffusion method. Using synchrotron radiation at
      station BL44B2 of SPring-8, Japan, BVR diffraction data were collected to 1.6 A
      resolution. Crystals belong to the orthorhombic space group P2(1)2(1)2(1), with
      unit-cell parameters a = 58.89, b = 70.41, c = 87.76 A. The complete
      determination of the crystallographic structure is currently in progress using
      MAD (multiwavelength anomalous diffraction) data from an Ir-derivative crystal.

PMID- 10957641
TI  - Crystallographic study of intein homing endonuclease II encoded in the archaeal
      DNA polymerase gene.
AB  - Intein homing endonucleases are proteins spliced out from a precursor protein and
      site-specific enzymes that make double-strand breaks in inteinless alleles.
      Crystals of intein homing endonuclease II from the hyperthermophilic archaeon
      Pyrococcus kodakaraensis strain KOD1 (PI-PkoII) have been grown at room
      temperature using ammonium sulfate as a precipitant. The diffraction pattern of
      the crystal extends to 3.0 A resolution at room temperature upon exposure to
      synchrotron X-rays at KEK-PF, Japan. The crystals have symmetry consistent with
      space group C222(1), with unit-cell parameters a = 107.6, b = 150.5, c = 146.8 A.
      A full set of X-ray diffraction data were collected to 3.0 A Bragg spacing from a
      native crystal with an overall R(merge) of 4.8% and a completeness of 96.6%.

PMID- 10957642
TI  - Purification, crystallization and initial X-ray analysis of the head-tail
      connector of bacteriophage phi29.
AB  - The head-tail connector of bacteriophage phi29, an oligomer of gene product 10
      (gp10), was crystallized into various forms. The most useful of these were an
      orthorhombic P22(1)2(1) form (unit-cell parameters a = 143.0, b = 157.0, c =
      245.2 A), a monoclinic C2 form (a = 160.7, b = 143.6, c = 221.0 A, beta = 97.8
      degrees ) and another monoclinic C2 form (a = 177.0, b = 169.1, c = 185.2 A, beta
      = 114.1 degrees ). Frozen crystals diffracted to about 3.2 A resolution. There is
      one connector per crystallographic asymmetric unit in each case. Rotation
      functions show the connector to be a dodecamer. Translation functions readily
      determined the position of the 12-fold axis in each unit cell. The structure is
      being determined by 12-fold electron-density averaging within each crystal and by
      averaging between the various crystal forms.

PMID- 10957643
TI  - Purification, crystallization and preliminary crystallographic data for rat
      cytosolic selenocysteine 498 to cysteine mutant thioredoxin reductase.
AB  - Mammalian cytosolic thioredoxin reductase is a homodimer of 55 kDa subunit
      containing an essential penultimate selenocysteine residue. An active analogue of
      the rat enzyme in which cysteine replaces selenocysteine has been expressed in
      Escherichia coli cells at high levels and purified to homogeneity. The pure
      enzyme contains one FAD per subunit and shows spectral properties identical to
      that of the wild-type thioredoxin reductase. The isolated enzyme in its oxidized
      and reduced forms or the enzyme complexed with NADP(+) was crystallized by the
      hanging-drop vapour-diffusion method. The diffraction pattern extends to 3 A
      resolution. The crystals are monoclinic, space group P2(1), with unit-cell
      parameters a = 78.9, b = 140.5, c = 170.8 A, alpha = 94.6 degrees. There are
      three dimeric molecules in the asymmetric unit.

PMID- 10957644
TI  - Crystallization and preliminary X-ray diffraction studies of the peptide
      methionine sulfoxide reductase from Escherichia coli.
AB  - Peptide methionine sulfoxide reductase mediates the reduction of protein
      sulfoxide methionyl residues back to methionines and could thus be implicated in
      the antioxidant defence of organisms. Hexagonal crystals of the Escherichia coli
      enzyme (MsrA) were obtained by the hanging-drop vapour-diffusion technique. They
      belong to space group P6(5)22, with unit-cell parameters a = b = 102.5, c = 292.3
      A, gamma = 120 degrees. A native data set was collected at 1.9 A resolution.
      Crystals of selenomethionine-substituted MsrA were also grown under the same
      crystallization conditions. A three-wavelength MAD experiment has led to the
      elucidation of the positions of the Se atoms and should result in a full
      structure determination.

PMID- 10957645
TI  - Crystallization and preliminary X-ray crystallographic analysis of water channel
      AQP1.
AB  - Aquaporin-1 (AQP1), a water channel from bovine red blood cells has been
      deglycosylated, purified to homogeneity and crystallized in a form suitable for X
      ray crystallographic study. Crystals are grown using polyethylene glycol as
      precipitant and belong to the tetragonal space group I422, with unit-cell
      parameters a = b = 93.4, c = 180.4 A. The crystals diffract beyond 2.2 A
      resolution.

PMID- 10957646
TI  - Identification of a potential metal cation-pi binding site in the structure of a
      thermophilic Bacillus stearothermophilus triosephosphate isomerase mutant.
AB  - A potential metal cation-pi interaction between a sodium cation (Na(+)) and the
      indole ring of a tryptophan residue was detected in the crystallographic
      structure (2 A) of the thermophilic Bacillus stearothermophilus triosephosphate
      isomerase H12N/K13G mutant (bTIMmut). The cation-pi binding site is located near
      the surface of the protein, the alkali metal ion facing the benzo ring of Trp9.
      The presence of Phe21 and Glu17 close to Trp9 could indicate an additional role
      for those residues in the stability of the sodium-indole interaction. The sodium
      cation lies in a position that is occupied by CE and NZ of Lys13 in the wild-type
      structure.

PMID- 10957647
TI  - Carotid-subclavian bypass grafting with polytetrafluoroethylene grafts for
      symptomatic subclavian artery stenosis or occlusion: a 20-year experience.
AB  - BACKGROUND AND PURPOSE: Since the advent of subclavian artery percutaneous
      transluminal angioplasty/stenting, several authorities advocate it as the
      treatment of choice for patients with subclavian artery disease, claiming results
      equal to or better than those of reconstructive vascular surgery. However, most
      of their quoted surgical series included patients who may have other
      brachiocephalic disease who were treated nonuniformly by means of various bypass
      grafts with different grafts in the same series (eg, Dacron,
      polytetrafluoroethylene [PTFE], or vein). In this study, we analyze the long-term
      results of a large series of carotid-subclavian bypass grafts for subclavian
      artery disease in which PTFE was uniformly used; the study can be used as a
      future reference to compare the results of subclavian artery percutaneous
      transluminal angioplasty/stenting. PATIENT POPULATION AND METHODS: Fifty-one
      patients with symptomatic subclavian artery disease (40 occlusions and 11
      stenoses) who were treated with carotid-subclavian bypass grafts (PTFE [Goretex])
      during a 20-year period were analyzed. Graft patency was determined clinically
      and confirmed with Doppler scanning pressures and duplex ultrasound scanning. The
      cumulative patency, overall survival, and symptom-free survival rates were
      calculated with the life table method. RESULTS: Indications for surgery were arm
      ischemia in 34 patients (67%), vertebrobasilar insufficiency (VBI) in 27 (53%),
      and symptomatic subclavian steal in 7 (14%). A combination of arm ischemia and
      VBI occurred in 17 (33%) of these patients. The mean follow-up was 7.7 years with
      a median of 7.0 years (range, 1-19 years). The 30-day morbidity rate was 6%, with
      no perioperative stroke or mortality. Immediate relief of symptoms was achieved
      in 100% of patients; however, four patients (8%) had late recurrent symptoms
      (three with VBI). The primary patency and secondary patency rates at 1, 3, 5, and
      10 years were 100%, 98%, 96%, and 92% and 100%, 98%, 98%, and 95%, respectively.
      The symptom-free survival rates at 1, 3, 5, and 10 years were 100%, 96%, 82%, and
      47%, respectively. The overall survival rates at 1, 3, 5, and 10 years were 100%,
      98%, 86%, and 57%. The mean hospital stay was 3.5 days in the late 70s and 80s
      and 2.1 days in the 90s (P <. 001). CONCLUSIONS: Carotid-subclavian bypass grafts
      with PTFE grafts for subclavian artery disease are safe, effective, and durable
      and should remain the procedure of choice, particularly in good-risk patients.

PMID- 10957648
TI  - Intraoperative use of stents for the management of unacceptable distal internal
      carotid artery end points during carotid endarterectomy: short-term and midterm
      results.
AB  - PURPOSE: The management of unacceptable distal internal carotid artery (ICA) end
      points during carotid endarterectomy presents multiple dilemmas. The problem may
      be expeditiously solved by placement of an intraluminal stent, but reported
      clinical experience with this technique is limited. We retrospectively reviewed
      our experience with intraoperative stenting of the ICA for the correction of
      unacceptable distal ICA end points during carotid endarterectomy. We report our
      techniques and document the 30-day stroke morbidity-death rate and midterm
      outcomes of patients treated in this manner. METHOD: The records of 316
      consecutive carotid endarterectomies performed by the authors from January 1997
      through June 1999 were reviewed to identify those cases in which adjunctive
      intraoperative stenting of the distal ICA was used. For those patients treated
      with adjunctive ICA stents, we assessed technique, 30-day outcomes, and midterm
      outcomes. RESULTS: The 30-day combined stroke and death rate for the entire group
      of 316 carotid endarterectomies was 1.9%. Adjunctive distal ICA stents were used
      in 13 cases-4.1% of the total carotid endarterectomy group-for the correction of
      unacceptable distal ICA end points. All patients were male; the average age was
      70 years. Stents were used in 11 patients because in each of these cases the
      surgeon recognized an unacceptable end point and desired to limit further distal
      anatomic exposures and/or ischemia times. Stents were used in two patients to
      correct unexpected defects identified on intraoperative completion ultrasound
      scan. No 30-day periprocedural deaths, strokes, or transient ischemic attacks
      were observed. Average postoperative length of stay was 1.8 days (range, 1-5
      days). All patients have been followed up with serial carotid duplex scans, and
      one patient has been studied by means of angiography. No patients have died, and
      all remain in active clinical follow-up. Mean length of follow-up has been 15
      months. No significant asymptomatic recurrences have been observed, but one
      patient experienced an isolated episode of amaurosis fugax without demonstrable
      restenosis at 8 months postoperatively. CONCLUSION: Our experience suggests that
      the adjunctive use of stents for the correction of unacceptable distal ICA end
      points during carotid endarterectomy is safe and provides acceptable short-term
      and midterm outcomes. Continued follow-up will be required before this technique
      can be considered a primary choice rather than an expeditious secondary
      alternative in this infrequent clinical circumstance.

PMID- 10957649
TI  - Magnetic resonance angiography is an accurate imaging adjunct to duplex
      ultrasound scan in patient selection for carotid endarterectomy.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy of magnetic
      resonance angiography (MRA) for categorizing the severity of carotid disease
      relative to duplex ultrasound scan and cerebral contrast arteriography (CA) to
      determine if MRA imaging could replace the need for cerebral angiography in cases
      of indeterminate or inadequate duplex scan imaging. METHODS: Seventy-four carotid
      bifurcations in 40 patients undergoing 45 carotid endarterectomies from 1996 to
      1998 were imaged with duplex ultrasound scan; MRA (two-dimensional neck and three
      dimensional intracranial, time-of-flight technique); and biplanar, digital
      subtraction cerebral arteriography. Studies were blindly reviewed by one reader
      who used established threshold velocity criteria for the duplex scan and the
      North American Symptomatic Carotid Endarterectomy Trial method for MRA and CA to
      determine the percentage of diameter reduction of the internal carotid artery
      (ICA). Disease severity was grouped into four categories (< 50%, 50%-74%, 75%-99%
      stenosis and occlusion), and the results of MRA and duplex ultrasound scan were
      compared with CA. RESULTS: Sensitivity, specificity, positive predictive value,
      and negative predictive value for detection of > 50% ICA stenosis were 100%, 96%,
      98%, and 100% for MRA and 100%, 72%, 88%, and 100% for duplex ultrasound scan,
      respectively; similarly, for detection of > 75% ICA stenosis values were 100%,
      77%, 76%, and 100% for MRA and 90%, 74%, 72%, and 91% for duplex ultrasound scan,
      respectively. Both MRA and duplex ultrasound scan accurately differentiated all
      cases of > 95% stenosis (n = 7) from occlusion (n = 4). Short length ICA flow
      gaps were present on MRA in all cases of 75% to 99% stenosis and one half of
      cases of CA-defined 50% to 74% stenosis. In patients with 50% to 74% stenosis,
      the mean angiographic stenosis was significantly greater when a flow gap was
      present on MRA (64% +/- 6%) versus no flow gap (57% +/- 7%) (P =.04). There was
      overall agreement among duplex ultrasound scan, MRA, and CA in 73% of carotids
      imaged. Of the 24% discordant results between MRA and duplex ultrasound scan, MRA
      correctly predicted disease severity in all cases, and inaccurate duplex
      ultrasound scan results were due to overestimation in 83% of cases. The operative
      plan was altered by CA findings in only one patient (2%) after duplex ultrasound
      scan and MRA. CONCLUSIONS: MRA can accurately categorize the severity of carotid
      occlusive disease. Duplex ultrasound scan facilitates patient selection for
      carotid endarterectomy in most cases, but adjunct use of MRA improves diagnostic
      accuracy for > 75% stenoses and may obviate the need for cerebral arteriography
      when duplex scan results are inconclusive or demonstrate borderline disease
      severity.

PMID- 10957650
TI  - Watchful waiting in cases of small abdominal aortic aneurysms- appropriate for
      all patients?
AB  - OBJECTIVE: The purpose of this study was to determine the effect of patient
      compliance on a program of watchful waiting in cases of small abdominal aortic
      aneurysms and to document the proportion of patients who become prohibitive
      operative risks during follow-up. STUDY DESIGN: A retrospective review was
      conducted at a regional military veterans medical center. The subjects were 101
      male military veterans with abdominal aortic aneurysms measuring less than 5 cm
      who did not have medical contraindications to operative repair. The main outcome
      measures were (1) the proportion of patients who missed three scheduled
      radiologic tests in a row despite written notifications mailed to their homes and
      (2) the proportion of compliant patients who had medical illnesses and became
      prohibitive operative risks during follow-up. RESULTS: During a follow-up (mean
      +/- SEM) of 34 +/- 2 months, 69 patients (69%) were fully compliant with the
      watchful waiting program and underwent a mean of 4.5 +/- 0.3 radiologic tests.
      There were no abdominal aortic aneurysm ruptures in this subgroup. Twenty-five
      patients (36%) had indications for abdominal aortic aneurysm repair, and 28 (41%)
      have not met the criteria for repair. Sixteen (23%) of the 69 compliant patients
      developed prohibitive medical risks during follow-up; eight (50%) of these 16
      patients died, all of the causes unrelated to their abdominal aortic aneurysms.
      Thirty-two (32%) of the 101 study subjects were noncompliant with the watchful
      waiting program. Twenty-seven (84%) of the noncompliant patients did not keep any
      scheduled appointments, and five (16%) were lost after one or two examinations.
      Three of the noncompliant patients experienced documented abdominal aortic
      aneurysm rupture, and it is suspected in a fourth. Direct contact was made with
      28 (88%) of these patients or their families; all acknowledged having received
      written notifications regarding their watchful waiting program tests and had
      decided not to continue with surveillance for a variety of socioeconomic reasons.
      Between the 69 compliant patients and the 32 noncompliant patients, there were no
      differences with respect to mean age (70 +/- 1 years vs 73 +/- 2 years), distance
      from home of record to the hospital (62 +/- 14 miles vs 73 +/- 23 miles), or
      abdominal aortic aneurysm size at initial detection (3.75 +/- 0.5 cm vs 3.8 +/-
      0.5 cm). CONCLUSIONS: Watchful waiting programs are imperfect and highly reliant
      on the motivation levels and means of the individual patients. Watchful waiting
      is reasonable among compliant patients with abdominal aortic aneurysms, inasmuch
      as fewer than half will meet the criteria for intervention within a mean of 3
      years. Approximately one fourth of these patients will have medical
      contraindications to abdominal aortic aneurysm repair during follow-up, and many
      of these will die of causes other than abdominal aortic aneurysm rupture. In our
      experience, one third of candidates for watchful waiting programs are unable to
      participate and are at risk of rupture. These patients need special attention so
      that the reasons for their noncompliance can be determined, and they may be
      candidates for earlier intervention.

PMID- 10957651
TI  - Long-term outcome after treatment of aortic graft infection with staged extra
      anatomic bypass grafting and aortic graft removal.
AB  - OBJECTIVE: The purpose of this study was to determine long-term outcome in
      patients with infected prosthetic aortic grafts who were treated with extra
      anatomic bypass grafting and aortic graft removal. METHODS: Between January 1989
      and July 1999, 36 patients were treated for aortic graft infection with extra
      anatomic bypass grafting and aortic graft removal. Extra-anatomic bypass graft
      types were axillofemoral femoral (5), axillofemoral (26; bilateral in 20),
      axillopopliteal (3; bilateral in 1) and axillofemoral/axillopopliteal (2). The
      mean follow-up was 32.3 +/- 4. 8 months. RESULTS: Four patients (11%) died in the
      postoperative period, and two patients died during follow-up as a direct
      consequence of extra-anatomic bypass grafting and aortic graft removal (one died
      7 months after extra-anatomic bypass graft failure, one died 36 months after
      aortic stump disruption). One additional patient died 72 months after failure of
      a subsequent aortic reconstruction, so that the overall treatment-related
      mortality was 19%, whereas overall survival by means of life table analysis was
      56% at 5 years. No amputations were required in the postoperative period, but
      four patients (11%) required amputation during follow-up. Twelve patients (35%)
      had extra-anatomic bypass graft failure during follow-up, and six patients
      underwent secondary aortic reconstruction (thoracobifemoral [2], iliofemoral [2],
      femorofemoral [2]). However, with the exclusion of patients undergoing
      axillopopliteal grafts (primary patency 0% at 7 months), only seven patients
      (25%) had extra-anatomic bypass graft failure, and only two patients required
      amputation (one after extra-anatomic bypass graft removal for infection, one
      after failure of a secondary aortic reconstruction). Furthermore, primary and
      secondary patency rates by means of life table analysis were 75% and 100% at 41
      months for axillofemoral femoral grafts and 64% and 100% at 60 months for
      axillofemoral grafts. Only one patient required extra-anatomic bypass graft
      removal for recurrent infection, and only one late aortic stump disruption
      occurred. CONCLUSIONS: Staged extra-anatomic bypass grafting (with axillofemoral
      bypass graft) and aortic graft removal for treatment of aortic graft infection
      are associated with acceptable early and long-term outcomes and should remain a
      primary approach in selected patients with this grave problem.

PMID- 10957652
TI  - Renal duplex sonography: main renal artery versus hilar analysis.
AB  - OBJECTIVE: The purpose of this study was to compare the accuracy of main renal
      artery Doppler scanning interrogation and hilar analysis to diagnose
      hemodynamically significant renal artery disease. METHODS: From January 1998 to
      August 1999, 41 patients had renal duplex sonography with both main renal artery
      interrogation and hilar analysis followed by angiography. They form the basis of
      this review. The sample consisted of 24 men and 17 women, with a mean age of 68.9
      +/- 10.2 years, who provided 80 kidneys for comparative analysis. Significant
      renal artery disease revealed through angiography was defined as >/= 60% diameter
      reducing stenosis or occlusion. Peak systolic velocity (PSV) (in meters per
      second) and the presence of poststenotic turbulence (PST) were determined from
      main renal artery interrogation. Acceleration time (AT) (in milliseconds) was
      measured by means of hilar analysis. Significant renal artery stenosis was
      defined by a PSV of 2.0 m/s or more and a PST or an AT more than 100 ms.
      Sensitivity analyses of both PSV and AT were examined, and 95% CIs were computed.
      Receiver operating characteristic curves were used to estimate optimal values for
      PSV and AT. RESULTS: Angiography revealed hemodynamically significant
      fibromuscular dysplasia in 5 kidneys (4 patients), atherosclerotic stenosis >/=
      60% in 48 kidneys (30 patients), and renal artery occlusion in 4 kidneys (4
      patients). Kidneys with significant renal artery stenosis had a higher PSV (2.54
      +/- 0.11 vs 1.28 +/- 0.08, P <.001) and AT (82.43 +/- 7.2 vs 30.0 +/- 2.8, P
      <.001) compared with those without stenosis. Compared with angiography, a PSV of
      2.0 m/s or more and PST demonstrated a sensitivity of 91%, specificity of 96%,
      and overall accuracy of 92% for detection of significant renal artery stenosis.
      Two of five studies with false-negative results reflected diseased polar vessels.
      By contrast, AT of more than 100 ms had a sensitivity of 32%, specificity of
      100%, and overall accuracy of 54%. Receiver operating characteristic curve
      analysis revealed a PSV of more than 1.8 m/s and an AT of 58 ms or greater as
      optimal values. With an AT of 58 ms or more, the sensitivity was 58%, and
      specificity was 96%, with an overall accuracy of 70%. There were no apparent
      associations between PSV or AT and type or location of renal artery lesion, serum
      creatinine level, or end-diastolic ratio. CONCLUSION: Main renal artery
      interrogation is an accurate screening test to detect significant stenosis or
      occlusion of the main renal artery. Hilar analysis alone does not provide
      sufficient sensitivity to be used as a sole screening study. Neither method
      detects the presence of renovascular disease associated with polar vessels.

PMID- 10957653
TI  - Management of ischemic nephropathy: dialysis-free survival after surgical repair.
AB  - PURPOSE: This retrospective review describes the surgical management of
      consecutive patients with severe hypertension and ischemic nephropathy due to
      atherosclerotic renovascular disease. METHODS: From January 1987 through December
      1998, a total of 590 patients underwent operative renal artery repair at our
      center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66
      +/- 8 years) with atherosclerotic renovascular disease and preoperative serum
      creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in
      renal function was determined from glomerular filtration rates estimated from
      preoperative and postoperative serum creatinine. The influence of selected
      preoperative parameters and renal function response on time to dialysis and
      dialysis-free survival was determined by a proportional hazards regression model.
      RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149
      patients underwent bilateral repair, including repair to a solitary kidney in 17
      cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies
      were performed in these patients. After surgery, there were 17 deaths (7.3%) in
      the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard
      ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard
      ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations
      with perioperative mortality. With a change of 20% or more in EGFR being
      considered significant, 58% of patients had improved renal function, including 27
      patients removed from dialysis dependence; function was unchanged in 35% and
      worsened in 7%. Follow-up death from all causes or progression to dialysis
      dependence demonstrated a significant and independent association with early
      renal function response. Both patients whose function was unchanged (P =.005;
      hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P
      =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or
      dialysis dependence. For patients with unchanged renal function after operation,
      risk of death or dialysis demonstrated a significant interaction with
      preoperative renal function. In addition to severe preoperative renal
      dysfunction, diabetes mellitus demonstrated a significant and independent
      association with follow-up death or dialysis. CONCLUSION: Surgical correction of
      atherosclerotic renovascular disease can retrieve excretory renal function in
      selected hypertensive patients with ischemic nephropathy. Patients with improved
      renal function had a significant and independent increase in dialysis-free
      survival in comparison with patients whose function was unchanged and patients
      whose function was worsened after operation. These results add further evidence
      in support of a prospective, randomized trial designed to define the value of
      renal artery intervention in patients with ischemic nephropathy.

PMID- 10957654
TI  - Continued experience with physical examination alone for evaluation and
      management of penetrating zone 2 neck injuries: results of 145 cases.
AB  - PURPOSE: Our preliminary experience with physical examination alone in the
      evaluation of penetrating zone 2 neck injuries for vascular trauma was previously
      reported in 28 patients over a 2-year period (1991-1993). The purpose of the
      current study was to examine the results of this approach in a much larger group
      of patients over an 8-year period. METHODS: The medical records for all patients
      admitted to our level I trauma center (all of them entered into our prospective
      protocol) between December 1991 and April 1999 with penetrating zone 2 neck
      trauma were reviewed for their initial presentation and any documented vascular
      injury. RESULTS: A total of 145 patients made up the study group; in 30 of these
      patients, the penetrating trajectory also traversed zone 1 or 3. Thirty-one
      patients (21%) had hard signs of vascular injury (active bleeding, expanding
      hematoma, bruit/thrill, pulse deficit, central neurologic deficit) and were taken
      immediately to the operating room; 28 (90%) of these 30 patients had either major
      arterial or venous injuries requiring operative repair (the false-positive rate
      for physical examination thus being 10%). Of the 114 patients with no hard signs,
      23 underwent arteriography because of proximity of the injury to the vertebral
      arteries or because the trajectory included another zone. Of these 23
      arteriograms, three showed abnormalities, but only one required operative repair.
      This case had no complications relating to the initial delay. The remaining 91
      patients with no hard signs were observed without imaging or surgery for a
      minimum of 23 hours, and none had any evidence of vascular injury during
      hospitalization or during the initial 2-week follow-up period (1/114; false
      negative rate for physical examination, 0.9%). CONCLUSIONS: This series confirms
      the earlier report indicating that patients with zone 2 penetrating neck wounds
      can be safely and accurately evaluated by physical examination alone to confirm
      or exclude vascular injury. The missed-injury rate is 0.7% (1/145) with this
      approach, which is comparable to arteriography in accuracy but less costly and
      noninvasive. Long-term follow-up is needed to confirm this management option.

PMID- 10957655
TI  - Prophylactic vena caval filters in trauma: the rest of the story.
AB  - OBJECTIVE: The purpose of this study was to describe outcomes for patients with
      trauma who had vena caval filters placed in the absence of venous thromboembolic
      disease (group P) and compare them with outcomes for patients with trauma who had
      filters placed after either deep venous thrombosis or pulmonary embolism (group
      T). DESIGN: The study is a case series of consecutive patients who received vena
      caval filters after traumatic injury. Data were collected prospectively at the
      time of filter placement from reports of diagnostic studies obtained for clinical
      indications and during the annual follow-up examinations. Event rate findings are
      based on objective tests. Data were obtained from the Michigan Vena Cava Filter
      Registry. RESULTS: Filters were placed in 385 patients with trauma; 249 of these
      filters were prophylactic (group P). Event rates were similar in the two groups.
      New pulmonary embolism was diagnosed in 1.5% of the patients in group P and 2% of
      the patients in group T. Caval occlusion rates were 3.5% for group P and 2.3% for
      group T. In all, 15.6% of the patients in group P had deep venous thrombosis or
      pulmonary embolism after placement. The frequencies of lower extremity swelling
      and use of support hose were higher in group T than in group P (43% vs 25% and
      25% vs 3.5%, respectively; P <.005). Outcomes were comparable in the two groups
      with respect to mechanical stability of the filter. CONCLUSIONS: The prophylactic
      indication for vena caval filter placement in patients with trauma is associated
      with a low incidence of adverse outcomes while providing protection from fatal
      pulmonary embolism. The current challenge is to limit the number of unnecessary
      placements through improved methods of risk stratification.

PMID- 10957656
TI  - The consequences of a failed femoropopliteal bypass grafting: comparison of
      saphenous vein and PTFE grafts.
AB  - OBJECTIVES: Although there are numerous reports comparing saphenous vein (SV) and
      polytetrafluoroethylene (PTFE) with respect to the patency rates for
      femoropopliteal bypass grafts, the clinical consequences of failed grafts are not
      as well described. This study compares the outcomes of failed SV and PTFE grafts
      with a specific emphasis on the degree of acute limb ischemia caused by graft
      occlusion. METHODS: Over a 6-year period, 718 infrainguinal revascularization
      procedures were performed, of which 189 were femoropopliteal bypass grafts (SV,
      108; PTFE, 81). Society for Vascular Surgery/International Society for
      Cardiovascular Surgery (SVS/ISCVS) standardized runoff scores were calculated
      from preoperative arteriograms. Clinical categories of acute limb ischemia
      resulting from graft occlusion were graded according to SVS/ISCVS standards (I,
      viable; II, threatened; III, irreversible). Primary graft patency and limb
      salvage rates at 48 months were calculated according to the Kaplan-Meier method.
      RESULTS: Patients were well matched for age, sex, and comorbidities. Chronic
      critical ischemia was the operative indication in most cases (SV, 82%; PTFE, 80%;
      P =.85). Runoff scores and preoperative ankle-brachial index measurements were
      similar for the two groups (SV, 6.0 +/- 2.5 [SD] and 0.51 +/- 0.29; PTFE, 5.3 +/-
      2.8 and 0.45 +/- 0.20; P =.06 and P =.12). The distal anastomosis was made below
      the knee in 60% of SV grafts and 16% of PTFE grafts (P <.001). Grade II ischemia
      was more likely to occur after occlusion of PTFE grafts (78%) than after
      occlusion of SV grafts (21%; P =.001). Emergency revascularization after graft
      occlusion was required for 28% of PTFE failures but only 3% of SV graft failures
      (P <.001). Primary graft patency at 48 months was 58% for SV grafts and 32% for
      PTFE grafts (P =.008). Limb salvage was achieved in 81% of SV grafts but only 56%
      of PTFE grafts (P =.019). CONCLUSIONS: Patients undergoing femoropopliteal bypass
      grafting with PTFE are at greater risk of ischemic complications from graft
      occlusion and more frequently require emergency limb revascularization as a
      result of graft occlusion than patients receiving SV grafts. Graft patency and
      limb salvage are superior with SV in comparison with PTFE in patients undergoing
      femoropopliteal bypass grafting.

PMID- 10957657
TI  - Influence of hormone replacement therapy on graft patency after femoropopliteal
      bypass grafting.
AB  - OBJECTIVE: Thromboembolic events are more frequent in women with established
      cardiovascular disease who are receiving hormone replacement therapy (HRT). The
      effect of HRT on the outcome of women undergoing infrainguinal bypass grafting is
      unknown. The purpose of this study was to estimate the influence of risk factors,
      in particular HRT, on the outcome of women undergoing femoropopliteal bypass
      grafting. METHODS: During a 5-year period (between 1993 and 1998), 131
      femoropopliteal bypass graft procedures were performed in 106 women. The criteria
      prepared by the Ad Hoc Committee on Reporting Standards (Society for Vascular
      Surgery/North American Chapter of the International Society for Cardiovascular
      Surgery) were followed. Both univariate (Kaplan-Meier method) and multivariate
      analyses (Cox proportional hazards model) were used to determine the association
      among preoperative variables, graft patency, limb salvage, and survival. RESULTS:
      The average age of the patients was 66.4 years; 26% of the patients were
      receiving HRT. Indications for femoropopliteal bypass grafting were limb salvage
      (80%) and disabling claudication (20%). Autogenous vein was used in 48% of
      procedures, polytetrafluoroethylene (PTFE) in 49%, and PTFE-vein composite grafts
      in 3%. Distal popliteal anastomosis was above the knee in 52% and below the knee
      in 48%. Overall primary patency rate was 81% at 1 year, 65% at 3 years, and 56%
      at 5 years. Primary patency rates at 1, 3, and 5 years were 75%, 45%, and 23%,
      respectively, for HRT users and 84%, 72%, and 65%, respectively, for nonusers of
      HRT. Overall, cumulative 1- and 5-year limb salvage results were 96% and 92%,
      respectively, and long-term survival at 1, 3, and 5 years was 96%, 86% and 74%,
      respectively. With univariate and Cox regression analyses, HRT was identified as
      the only independent predictor of reduced primary graft patency (Kaplan-Meier
      method, log-rank test, P =.004; relative risk, 2.5; 95% CI, 1.3-4.8). Women
      receiving HRT who underwent a procedure with PTFE had the lowest primary graft
      patency rates (relative risk, 3.4; 95% CI, 1. 5-7.8; P =.006). CONCLUSIONS: Women
      undergoing femoropopliteal bypass graft procedures who are receiving HRT have
      significantly reduced primary graft patency rates. The risk of graft failure
      increases when prosthetic materials are used.

PMID- 10957658
TI  - Endovascular repair of abdominal aortic aneurysms: eligibility rate and impact on
      the rate of open repair.
AB  - OBJECTIVE: The purpose of this study was to determine the rate of eligibility
      among patients with abdominal aortic aneurysms (AAAs) considered for endovascular
      repair and to examine the effect of an endovascular program on the institutional
      pattern of AAA repair. METHODS: All patients evaluated for endovascular AAA
      repair since the inception of an endovascular program were reviewed for
      determination of eligibility rates and eventual treatment. Open AAA repairs were
      categorized as simple (uncomplicated infrarenal), complex (juxtarenal,
      suprarenal, thoracoabdominal, infected), or ruptured, and their rates before and
      after initiation of an endovascular program were compared. RESULTS: Over 3 years,
      324 patients were considered for endovascular AAA repair; 176 (54%) were
      candidates, 138 (43%) were not candidates, and 10 (3%) did not complete the
      evaluation. The rate of eligibility increased significantly from 45% (66/148
      patients) during the first half of this period to 63% (110/176 patients) during
      the second half (P <. 001). Candidates were significantly younger (74.4 +/- 7.6
      years) than noncandidates (78.3 +/- 6.7 years) (P <.01), and their aneurysm
      diameter tended to be smaller (57.6 +/- 9.2 mm compared with 60.8 +/- 12.3 mm; P
      =.06). The most common reason for ineligibility was an inadequate proximal aortic
      neck. Of 176 candidates, 78% underwent endovascular repair, and 6% underwent open
      repair. Of 138 noncandidates, 56% underwent surgical repair. Over a period of 6
      years, 542 patients with AAAs (429 simple, 86 complex, 27 ruptured) underwent
      open repair. The total number and ratio of simple to complex open repairs for
      nonruptured aneurysms during the 3 years before the initiation of the
      endovascular program (213 simple, 44 complex) were not significantly different
      from the repairs over the subsequent 3-year period (216 simple, 42 complex).
      Similarly, no difference in the total number and the ratio of simple to complex
      open repairs was found between the first and the second 18-month periods since
      the initiation of the endovascular program. CONCLUSIONS: The rate of eligibility
      of patients with AAA for endovascular repair appears to be higher than previously
      reported. The presence of an active endovascular program has not decreased the
      number or shifted the distribution of open AAA repair.

PMID- 10957659
TI  - Enabling sutureless vascular bypass grafting with the exovascular sleeve
      anastomosis.
AB  - PURPOSE: We describe a technique for end-to-end sleeve anastomosis that may
      enable minimally invasive bypass grafting and characterize the tensile strength,
      stenosis rate, durability, and healing of the anastomosis. METHOD: An anastomotic
      device assembly consisting of a cable tie-type band with mobile teeth elements is
      mounted on the outer surface of a polytetrafluoroethylene graft. The graft is
      drawn over the artery resulting in a sleeve of vessel within the graft. As the
      band is tightened over an intraluminal obturator, the independently mobile
      anchoring teeth are driven through the graft into the artery. The tensile
      strength of the anastomosis was compared with sutured anastomosis during in vitro
      studies using cadaveric human femoral arteries. For in vivo studies on pigs and
      goats, we used a proximal exovascular sleeve anastomosis along with a distal
      sutured aortic anastomosis. Survival animals were studied by angiogram
      postoperatively and at the time of explantation. RESULTS: In vitro studies showed
      no difference in maximal tensile strength between sutured and exovascular
      anastomoses (10.5 +/- 2.7 lb vs 10.2 +/- 3.0 lb, P =.83). However, loss of
      continuous graft to artery interface occurred at lower loads in the sutured
      anastomoses (6.5 +/- 0.6 lb, P <.05). In total, all 24 pigs tested in nonsurvival
      or survival settings sustained a successful and leakproof anastomosis. Of the 13
      nonsurvival cases, maximal epinephrine-induced hypertension sustained over 15
      minutes (peak systolic blood pressure > 210-250 mm Hg) was tolerated without
      leakage in a subgroup of five animals (100%). All 11 survival pigs had no
      pseudoaneurysms or stenosis relative to sutured control anastomoses at 6 week
      explantation (8.2 +/- 1.25 mm vs 8.5 +/- 1.6 mm, P =.21). The three long-term
      survival goats had no pseudoaneurysm or stenosis after 40 weeks. Histologic
      examination confirmed healing of the aorta to graft with minimal neointimal
      hyperplasia. CONCLUSION: Exovascular sutureless anastomosis appears comparable to
      sutured anastomosis in stenosis rate, healing, and durability, with some
      advantages in tensile strength and rapidity of application.

PMID- 10957660
TI  - High prevalence of mild hyperhomocysteinemia in patients with abdominal aortic
      aneurysm.
AB  - PURPOSE: In vitro studies have recently demonstrated that homocysteine interacts
      with the aortic wall by inducing both elastolysis and endothelial perturbation.
      The aim of this study was to evaluate homocysteine plasma levels and their
      relationships with aortic diameter and endothelial damage in patients with
      abdominal aortic aneurysm. SUBJECTS AND METHODS: Fifty-eight consecutive male
      patients (mean age, 69.5 +/- 6.6 years; age range, 49-78 years) who underwent
      abdominal aortic aneurysm surgery were enrolled in the study. Twenty-two of 58
      patients had no clinical or instrumental evidence of atherosclerosis. Sixty
      control subjects were age matched and sex matched with the patients. In all of
      the subjects, we evaluated total homocysteine and thrombomodulin plasma levels
      and the distribution of the C677T methylenetetrahydrofolate reductase gene
      mutation. RESULTS: Hyperhomocysteinemia was found in 26 (48%) of the 58 patients
      with abdominal aortic aneurysm, and homocysteine plasma levels were significantly
      higher in patients than in control subjects (15.7 +/- 6.5 micromol/L vs 9.6 +/-
      3.9 micromol/L; P <. 0001). In addition, the subgroup of patients with abdominal
      aortic aneurysm who did not show evidence of atherosclerosis showed homocysteine
      plasma levels significantly higher than those in the controls (14.8 +/- 6.1
      micromol/L vs 9.6 +/- 3.9 micromol/L; P <. 001). A larger aneurysmal size was
      detected in hyperhomocysteinemic patients than in those with normal homocysteine
      plasma levels (5.09 +/- 0.84 cm vs 5.79 +/- 1.5 cm; P <.05). The genotype
      distribution of the C677T methylenetetrahydrofolate reductase mutation was as
      follows: TT 21%, TC 55%, and CC 24% in the patients; TT 10%, TC 58%, and CC 32%
      in the controls. Moreover, in patients a significant correlation (P <.005)
      between homocysteine plasma level and 677TT methylenetetrahydrofolate reductase
      genotype was found. Thrombomodulin plasma levels were significantly higher (P
      <.00005) in patients (median, 30 ng/mL; range, 10-164 ng/mL) than in controls
      (median, 19 ng/mL; range, 13-44 ng/mL), and thrombomodulin levels were
      significantly higher (P <.005) in hyperhomocysteinemic patients (median, 39.5
      ng/mL; range, 15-164 ng/mL) than in normohomocysteinemic patients (median, 27.5
      ng/mL; range, 10-85 ng/mL). In addition, in patients with abdominal aortic
      aneurysm, a direct significant correlation (P <.005) was found between
      homocysteine and thrombomodulin. CONCLUSIONS: These data indicate an association
      between the presence of AAA in patients selected for surgical treatment of AAA
      and elevated homocysteine plasma levels and suggest that homocysteine may induce
      endothelial perturbation and stimulation in these patients.

PMID- 10957661
TI  - External pneumatic compression and fibrinolysis in abdominal surgery.
AB  - INTRODUCTION: External pneumatic compression (EPC) devices prevent lower
      extremity deep venous thrombosis by increasing venous flow and thereby reducing
      stasis. Early studies suggested that they also enhance systemic fibrinolytic
      activity and thus prevent thrombus formation; more recent studies have been
      conflicting. The hypothesis of this study was that EPC devices enhance systemic
      fibrinolysis or reduce postoperative fibrinolytic impairment in patients
      undergoing abdominal surgical procedures. METHODS: Each of 48 patients (98% male;
      mean age, 67 years) undergoing major intra-abdominal surgical procedures (36
      bowel procedures, 12 aortic reconstructions) was prospectively randomized to one
      of three treatments for deep venous thrombosis prophylaxis: subcutaneous heparin
      injections (HEP group), use of a thigh-length sequential EPC device (EPC group),
      or both (HEP + EPC group). Antecubital venous samples were collected for
      measurement of systemic fibrinolytic activity on the day before surgery, after
      induction of anesthesia but before prophylaxis was initiated, and on
      postoperative days 1, 3, and 5. Fibrinolysis was assessed through measurement of
      the activities of the rate limiting fibrinolytic activator, tissue plasminogen
      activator, and its inhibitor plasminogen activator inhibitor-1 with amidolytic
      methods. RESULTS: On the day before surgery, plasminogen activator inhibitor-1
      activity was elevated in all groups in comparison with that in age-matched and
      sex-matched controls (20.3 +/- 0.6 AU/mL). In the HEP group, plasminogen
      activator inhibitor-1 activity was further elevated above the value for the day
      before surgery on postoperative day 1 (28.5 +/- 4.3 AU/mL; P =.04) and
      postoperative day 3 (25.1 +/- 1.9 AU/mL; P =.07). No significant decrease in
      plasminogen activator inhibitor-1 activity occurred in either group treated with
      EPC devices in comparison with the HEP group at any time. There were no changes
      in tissue plasminogen activator activity postoperatively in the HEP group and no
      significant increases in either EPC group at any point. CONCLUSIONS: Reduced
      systemic fibrinolytic activity ("fibrinolytic shutdown") occurred in these
      patients after abdominal surgery; it was manifested as increased plasminogen
      activator inhibitor-1 activity. EPC devices did not enhance systemic fibrinolysis
      or prevent postoperative shutdown either by decreasing plasminogen activator
      inhibitor-1 activity or by increasing tissue plasminogen activator activity.
      These data suggest that EPC devices do not prevent deep venous thrombosis by
      fibrinolytic enhancement; effective prophylaxis is achieved only when the devices
      are used in a manner that reduces lower extremity venous stasis.

PMID- 10957662
TI  - High endogenous estradiol is associated with increased venous distensibility and
      clinical evidence of varicose veins in menopausal women.
AB  - OBJECTIVE: The purpose of this study was to determine if there is an association
      between elevated sex hormones (ie, serum estradiol, sex hormone binding globulin
      [SHBG], testosterone) and increased venous distension and clinical evidence of
      varicose veins in menopausal women. METHODS: Participants were 104 healthy
      volunteer menopausal women, aged 48 to 65 years, who were not undergoing hormonal
      treatment. Of these 104, 14 were excluded from analyses because their estradiol
      levels were compatible with a premenopausal condition (4), because they had
      missing values for insulin concentration (5), and because they did not show up at
      venous vessel examination (5). Patients underwent a physical examination to
      determine the presence of varicose veins; a venous strain-gauge plethysmographic
      examination to compute instrumental measures of venous distensibility; and
      laboratory analyses of blood so serum testosterone, estradiol, SHBG, glucose, and
      insulin could be measured. There were also prevalence ratios and odds ratios used
      to test the presence of an association between biochemical and instrumental
      variables. RESULTS: Serum levels of estradiol in the upper tertile of the
      frequency distribution were significantly associated with clinical evidence of
      varicose veins (prevalence odds ratios 3.6; 95% CI 1.1-11.6) and with increased
      lower limb venous distensibility (prevalence odds ratios 4.4; 95% CI 1.2-15.5).
      No association was found for SHBG and testosterone. CONCLUSIONS: Our finding that
      high serum levels of estradiol are associated with clinical evidence of varicose
      veins and instrumental measurements indicating increased venous distensibility in
      menopausal women suggests that endogenous estrogens may play a role in the
      development of this very common venous vessel abnormalities.

PMID- 10957663
TI  - Factors predicting prolonged length of stay after carotid endarterectomy.
AB  - BACKGROUND: Over the last several years, implementation of critical pathways in
      patients undergoing carotid endarterectomy has decreased postoperative length of
      stay significantly. Discharge the day after surgery has become commonplace in
      many centers, including our own. Unfortunately, managed care may interpret this
      refinement as a standard of care and limit reimbursement or even disallow
      admissions extending beyond 1 day. We therefore examined our carotid registry to
      identify risk factors associated with postoperative length of stay exceeding 1
      day. METHODS: We retrospectively reviewed all patients undergoing carotid
      endarterectomy at our academic center from May 1996 through April 1999. Combined
      procedures and patients undergoing subsequent noncarotid-related procedures on
      those admissions were excluded. The charts were inspected for atherosclerosis
      risk factors, including sex and age, specific attending surgeon, side of the
      surgery, use of intravenous vasoactive drugs, actual preoperative blood pressure,
      and presence of neurologic symptoms or postoperative complications. Multiple
      regression analysis was performed on all collected variables. Statistical
      significance was inferred for P less than.05. RESULTS: A total of 188 patients
      met the study criteria and had complete, retrievable medical records. A mean
      postoperative length of stay of 1.65 +/- 0.08 days and a mean total length of
      stay of 2.17 +/- 0.14 days were observed. Fifty-seven percent of patients went
      home the day after surgery. There was a 1.6% stroke-mortality rate. Significant
      predictors of a prolonged stay, listed in order of decreasing importance on the
      basis of their calculated contribution to prolonging the postoperative length of
      stay, are as follows (P value; beta coefficient): postoperative complications
      (<.0001; 1.03), age > 79 years (.008; 0.547), diabetes mellitus (.011; 0.407),
      female sex (.007; 0.398), and intravenous vasodilator requirement (. 035; 0.382).
      Other atherosclerosis risk factors, prior neurologic symptoms, the postoperative
      use of vasopressors, and reoperative surgery did not contribute to extended
      length of stay. CONCLUSIONS: Discharge on the first postoperative day is feasible
      in many, but not all, patients undergoing carotid endarterectomy. Our data help
      define subsets of patients at risk for prolonged postoperative stay. Targeting
      these subsets for preoperative medical and social interventions may allow safe
      early discharge more frequently.

PMID- 10957664
TI  - Apolipoprotein (a) fragments in relation to human carotid plaque instability.
AB  - PURPOSE: An elevated plasma level of lipoprotein (a) is an independent risk
      factor for atherothrombotic cardiovascular disease by yet undefined mechanisms.
      We have previously reported that matrix metalloproteinases cleave apolipoprotein
      (a) into 2 main fragments, F1 and F2, the latter (the C-terminal domain)
      exhibiting in vitro a high-affinity binding to extracellular matrix components,
      including fibrin(ogen). We therefore tested the hypothesis that the lipoprotein
      (a) matrix metalloproteinase-derived F2 is localized in potentially or
      morphologically unstable human carotid plaque at regions of increased matrix
      metalloproteinase activity. METHODS: Carotid plaques removed after endarterectomy
      (n = 18) were evaluated for structural features indicative of instability (thin
      fibrous cap, inflammation, and proximity of the necrotic core to the lumen); each
      plaque was classified as unstable (n = 10) or stable (n = 8). Western blot
      analysis was performed to quantitate apolipoprotein (a) and its fragments F1 and
      F2 in plaque extracts. Immunohistochemical staining was used to localize
      apolipoprotein (a) and its fragments within the atherosclerotic plaque. In situ
      zymography was used to determine regions of gelatinase (matrix metalloproteinase
      2 and matrix metalloproteinase 9) activity. RESULTS: Western blot analyses
      demonstrated a 2.5-fold higher density of F2 in unstable plaques than in stable
      plaques (3.07 +/- 1.9 vs 1.18 +/- 0.8; P <.05). In morphologically unstable
      plaques, there was preferential distribution of F2 within regions of fibrous cap
      inflammation and/or foam cell accumulation and within abluminal necrotic cores.
      In morphologically stable plaques, however, localization was predominantly found
      in the medial smooth muscle cells. Regions of enhanced matrix metalloproteinase 2
      and matrix metalloproteinase 9 activity co-localized with the transmural
      distribution of F2 within the plaque. CONCLUSIONS: These findings suggest that F2
      in regions of increased matrix metalloproteinase activity is a potential
      mechanism for superimposed thrombotic events in morphologically unstable human
      carotid plaques. The relationship between plasma lipoprotein (a) levels and
      accumulation of F2 and the potential correlation of F2 to human plaque disruption
      and thrombosis warrant further study.

PMID- 10957665
TI  - Predicting outcome of angioplasty and selective stenting of multisegment iliac
      artery occlusive disease.
AB  - BACKGROUND: Patients who require angioplasty and stenting of multiple iliac
      arterial segments often require reintervention to maintain long-term patency.
      Morphologic predictors and causes of failure are unknown. The purpose of the
      current study was to define arteriographic predictors of angioplasty and
      selective stent failure in the treatment of multisegment iliac occlusive disease.
      METHODS: All iliac segments (two common and two external) of 75 patients who
      underwent angioplasty and selective stent placement for multisegment iliac
      occlusive disease (>/= two segments) were scored through use of a modification of
      the Society of Cardiovascular and Interventional Radiology classification for
      iliac angioplasty (0 = no lesion; 4 = most severe). Total iliac score was
      calculated by summing scores from each segment. A separate external iliac score
      was calculated by adding only the external iliac scores. Arteriograms were
      reviewed initially and at the time of lesion recurrence and stratified by lesion
      location and previous intervention. RESULTS: The area of previous endovascular
      intervention was the site of recurrence in 75% of patients. New lesions,
      presumably a result of progressive atherosclerosis, occurred in 15% of patients,
      and lesions occurred in both new and previously treated iliac segments in 10% of
      patients. Only the external iliac score was an independent predictor of failed
      endovascular therapy despite reintervention. For patients with an external iliac
      score of 2 or less, the endovascular primary-assisted patency rates at 6, 12, and
      24 months were 96%, 92%, and 89%, respectively. This was improved in comparison
      with the 90%, 63%, and 45% patency rates observed in patients with an external
      iliac score of 3 or more (P =.001). Patients with an external iliac score of 3 or
      more had a significantly lower incidence of hemodynamic and clinical improvement
      after intervention and a threefold higher need for surgical inflow procedures
      than patients with an external iliac score of 2 or less. CONCLUSIONS: Lesion
      formation after treatment of multisegment iliac occlusive disease typically
      occurs in areas of prior intervention. The extent of external iliac disease can
      be used to stratify patients with multisegment iliac occlusive disease who will
      likely respond to endovascular treatment with a durable result. Patients with
      extensive external iliac disease (score >/= 3) have poor results after
      angioplasty and selective stenting as applied in this study, even with
      endovascular reintervention. They are ideal subjects for prospective comparative
      studies of competing initial therapies, including stenting, endografting, and
      aortobifemoral bypass grafting.

PMID- 10957666
TI  - Pregnancy-induced changes in lower extremity superficial veins: an ultrasound
      scan study.
AB  - OBJECTIVE: The purpose of this study was to follow changes in superficial veins
      of the lower extremities during pregnancy and the postpartum period in women with
      varicose veins. METHODS: This was a prospective study with the use of duplex
      scanning during the first and third trimesters of pregnancy and postpartum
      period. Competent veins were defined as veins with an absence of reflux, and
      incompetent veins were defined as veins with reflux. The diameter of the
      competent or incompetent greater saphenous vein (GSV) and lesser saphenous vein
      (LSV) was measured. The diameter of the largest varicose dilatations was measured
      in all three networks: GSV and its tributaries, LSV and its tributaries, and
      nonsaphenous varicose veins. RESULTS: Sixty-six women were studied prospectively
      (mean age, 32.2 +/- 4 years; 85 affected extremities). The diameter of competent
      and incompetent GSVs and competent LSVs increased between the first and third
      trimester (P <.001) and decreased between the third trimester and the postpartum
      period (P <.001). The diameter of the largest varicose dilatations of the GSV and
      its tributaries and nonsaphenous networks increased between the first and third
      trimester (P <.001) and decreased between the third trimester and the postpartum
      period (P <.001). No statistically significant variation of the diameter was
      demonstrated for any of these veins between the first trimester and the
      postpartum period. CONCLUSION: The diameters of competent and incompetent
      superficial veins increased during pregnancy and decreased during the postpartum
      period to return to their baseline values.

PMID- 10957667
TI  - Increased matrix metalloproteinase 2 expression in vascular smooth muscle cells
      cultured from abdominal aortic aneurysms.
AB  - OBJECTIVES: Recent evidence has implicated matrix metalloproteinase 2 (MMP-2) in
      the pathogenesis of aneurysms. The aim of this study was to examine MMP-2
      production and expression by aortic smooth muscle cells (SMCs) and dermal
      fibroblasts derived from patients with abdominal aortic aneurysms (AAAs).
      METHODS: Aortic SMCs and dermal fibroblasts were cultured from patients with AAAs
      or from age-matched controls with atherosclerosis. The production of MMP and
      tissue inhibitor of metalloproteinase into culture media was analyzed with the
      use of gelatin zymography, Western blotting, and enzyme-linked immunosorbent
      assay. Gene expression was analyzed with Northern blotting. RESULTS: All cells
      studied constitutively produced MMP-2. Aortic SMCs cultured from aneurysmal
      tissue expressed MMP-2 protein and messenger RNA at a significantly higher level
      than SMCs from controls (P =.008). Dermal fibroblasts from patients with AAAs
      expressed MMP-2 at a similar level to controls. In both cell types, tissue
      inhibitor of metalloproteinase 2 and membrane type 1-MMP were expressed at
      similar levels. CONCLUSIONS: These data suggested that the regulation of MMP-2
      gene expression was altered in the aortic SMCs of patients with aneurysms, but
      this finding was not repeated in other mesenchymal tissue.

PMID- 10957668
TI  - Regional differences in phorbol 12-myristate 13-acetate stimulation of PDGF
      production in the normal canine aorta.
AB  - OBJECTIVE: Platelet-derived growth factor (PDGF) is a potent smooth muscle cell
      mitogen implicated in the development of intimal hyperplasia and atherosclerosis.
      A regional variation in canine aortic production of PDGF (greater in the distal
      than in the proximal aorta) was demonstrated previously in organ culture. The
      response of aortic segments in organ culture, as well as of aortic endothelial
      cells and smooth muscle cells, to stimulators of PDGF secretion-phorbol 12
      myristate 13-acetate (PMA) and thrombin-was assessed to elucidate whether these
      regional variations were due to intrinsic differences in the abilities of cells
      to produce PDGF. METHODS: Proximal and distal aortic segments were removed from
      10 dogs and placed in organ culture, then treated with PMA or thrombin for 72
      hours. PDGF in the conditioned media was measured by radioreceptor assay.
      RESULTS: PDGF production in the distal, unstimulated aorta was 2.5-fold higher
      than that in the proximal aorta (P <.05). Treatment of the proximal aorta with 10
      nmol/L and 100 nmol/L PMA increased PDGF production twofold and threefold,
      respectively, whereas no increase with PMA treatment was seen in the distal
      aorta. After thrombin treatment, no increase in PDGF production was noted in the
      proximal aorta and only a minimal increase was noted in the distal aorta.
      Endothelial cells and smooth muscle cells (n = 6) were cultured from four aortic
      segments (ascending thoracic, descending thoracic, abdominal, and infrarenal) and
      treated with PMA. PDGF production by unstimulated endothelial cells from the
      infrarenal aorta was 2.5-fold higher (P <.01) than that from the ascending
      thoracic aorta. With PMA treatment, PDGF secretion increased in endothelial cells
      from all segments, the greatest percentage increase being observed in the
      proximal segments. Thrombin also increased PDGF release from endothelial cells,
      but with no regional variation. Unstimulated smooth muscle cells did not exhibit
      regional variation in PDGF production and did not increase PDGF secretion after
      treatment with PMA or thrombin. CONCLUSIONS: These findings suggest that
      endothelial cells in the aorta may have a differential capacity to produce PDGF
      in response to stimulants, reflecting intrinsic differences in endothelial cells
      from the proximal aorta versus the distal aorta, and this may account in part for
      the propensity of the distal aorta to develop atherosclerosis.

PMID- 10957669
TI  - Intracellular calcium response of endothelial cells exposed to flow in the
      presence of thrombin or histamine.
AB  - Endothelial cells line the vasculature and are exposed to mechanical shear stress
      because of blood motion. Previous studies have shown that endothelial cells
      respond to shear stress by altering their metabolism and genetic expression, but
      the mechanism for shear stress signal transduction remains unclear. In the
      current study, we investigated the role of intracellular Ca(2+) increases as a
      part of the shear stress signal transduction cascade. Primary human umbilical
      vein endothelial cells were loaded with the calcium-sensitive dye fura-2 and
      exposed to fluid flow in a parallel plate flow chamber in the presence of the
      inflammatory mediator histamine or the proteolytic enzyme thrombin. The
      initiation of shear stress (in the range of 0.2-20 dyne/cm(2)) in the absence of
      either agonist caused no increase in intracellular Ca(2+) levels. Cells exposed
      to either histamine (10(-9) to 10(-7) mol/l) or thrombin (0.02-0.2 u/ml) showed
      an intracellular calcium increase (20-150 nmol/L) that was dependent on the
      magnitude of the shear stress and on the concentration of agonist. In cells
      exposed to histamine and shear stress, the magnitude of the intracellular calcium
      increase was not altered, except at 10(-7) mol/L histamine. The time course of
      the response was significantly faster for arterial than for venous levels of
      shear stress at histamine concentrations from 10(-9) to 10(-7) mol/L. The
      magnitude of the [Ca(2+)](i) response was dependent on both the magnitude of the
      shear stress and the concentration of thrombin. At a thrombin concentration of
      0.2 U/mL, the increase in intracellular Ca(2+) was significantly greater at
      arterial levels of shear stress (6-20 dyne/cm(2)) than at venous levels of shear
      stress (0.2-1 dyne/cm(2)). Because we solved the governing mass balance equation
      to precisely determine the effect of flow on local agonist concentration, the
      alterations in the [Ca(2+)](i) response were not due to differences in mass
      transfer characteristics. These results demonstrate that even in a system in
      which the initiation of shear stress without agonist causes no detectable change
      in intracellular Ca(2+), the calcium response to agonists is changed, which
      suggests that the signal transduction pathway for shear stress acts
      synergistically with the thrombin and histamine signal transduction pathways.

PMID- 10957670
TI  - Dacron carotid patch infection: a report of eight cases.
AB  - From 1995 through 1998, we encountered eight patients with infected Dacron
      patches after previous carotid endarterectomy. Two of the original operations had
      been done elsewhere, but the six patients who were collected from our own series
      represented 0.5% of the 1258 carotid endarterectomies we performed and 1.8% of
      the 340 synthetic carotid patches we applied without any comparable infections
      among another 918 patients who received either vein patch angioplasty (n = 843)
      or primary arteriotomy closure (n = 74) during the same 4-year study period. With
      a single exception ("no growth"), bacterial cultures that were obtained at the
      time of the eight reoperations revealed Staphylococcus (n = 4) or Streptococcus
      (n = 3) species. All of the infected Dacron patches were removed and were
      replaced with saphenous vein patches (n = 5) or interposition grafts (n = 3),
      after which appropriate oral (n = 2) or intravenous (n = 6) antibiotics were
      administered for 2 to 6 weeks. No postoperative deaths occurred, but there were 2
      temporary cranial nerve injuries, 1 myocardial infarction, and 1 stroke that was
      related to preoperative angiography. A recurrent carotid infection has not
      developed in any of the eight patients during a mean follow-up interval of 16
      months (range, 3-36 months).

PMID- 10957671
TI  - Subclavian artery disruption resulting from endovascular intervention: treatment
      options.
AB  - Endovascular intervention is a commonly accepted form of treatment in patients
      with subclavian artery stenosis. Complications will undoubtedly occur as the
      utility of catheter-based intervention continues to rise. We report two cases of
      subclavian artery disruption as a result of endovascular intervention. One
      patient had contrast extravasation after the deployment of a balloon-expandable
      stent in a stenotic subclavian artery, and the arterial injury was successfully
      treated with balloon tamponade. A second patient had a large subclavian
      pseudoaneurysm 4 months after a balloon-expandable stent placement. Successful
      repair was achieved in this patient by means of arterial reconstruction with a
      prosthetic bypass graft. These cases illustrate different therapeutic methods of
      treating subclavian artery rupture due to endovascular intervention.

PMID- 10957672
TI  - Aneurysmal degeneration and late rupture of an aortorenal vein graft: case
      report, review of the literature, and implications for conduit selection.
AB  - The saphenous vein is among the most commonly used conduits for renal artery
      revascularization in adults. Vein grafts are more durable in the renal artery bed
      than in coronary and peripheral beds, and mechanisms of potential graft failure
      vary. Coronary vein grafts often fail because of atherosclerotic degeneration,
      whereas lower extremity grafts fail because of intimal hyperplasia or progression
      of underlying disease. In contrast, renal vein grafts may dilate over time but
      seldom fail. This may relate to the distinct hemodynamic environment of the renal
      bed with low-resistance, high-velocity blood flow. However, frank aneurysmal
      degeneration of renal vein grafts is rare with only a single report of rupture in
      the literature. We report an additional case of rupture of a late graft aneurysm
      and review the literature and our own experience with renal revascularization to
      underscore the rarity of this serious complication. The saphenous vein for
      aortorenal bypass grafting continues to be a favorable conduit for renal
      revascularization. Long-term duplex ultrasound scanning follow-up is recommended
      to survey the reconstructed artery and perhaps more important, to evaluate
      progression of subclinical disease in the contralateral renal artery.

PMID- 10957673
TI  - Percutaneous balloon fenestration in a case of traumatic abdominal aortic
      dissection with lower extremity ischemia.
AB  - A 38-year-old man was involved in a traffic accident and experienced a heavy blow
      to the abdomen. He had traumatic abdominal aortic dissection with right lower
      extremity ischemia. He underwent percutaneous balloon fenestration, which is safe
      and minimally invasive, for relief of right lower extremity ischemia. He has been
      working for 2 years without any signs of vascular compromise. Percutaneous
      balloon fenestration is one of the few treatments for traumatic abdominal aortic
      dissection.

PMID- 10957674
TI  - The case for an independent American Board of Vascular Surgery.

PMID- 10957675
TI  - Regarding "chronic venous insufficiency is associated with increased platelet and
      monocyte activation and aggregation".

PMID- 10957676
TI  - A Clinician's primer in human genetics: what nurses need to know.
AB  - This article provides nurses with general information about the structure and
      function of genes, metabolic and chromosomal disorders, and the inheritance of
      genetic conditions in families. It serves as a foundation for the remainder of
      this issue, which addresses the clinical application of genetic principles,
      genetic counseling and evaluation, and emerging genetic technologies. Nurses are
      present in all health care settings and care for individuals and families
      throughout their patient's life span. Nurses must therefore have adequate
      knowledge of human genetics so that they can identify individuals who may have a
      genetic condition or predisposition, and ensure that those individuals have
      access to the most current genetic diagnostics, treatment, and management
      therapeutics. With this knowledge, nurses can collect appropriate family
      histories, provide current genetic information, and support patients, families,
      and communities as they integrate this new information and technology into their
      daily lives.

PMID- 10957677
TI  - Genetic counseling and testing: implications for clinical practice.
AB  - As the genetic basis of many human illnesses becomes known, the provision of
      genetic counseling to individuals and family has gained importance. Patients
      concerned about genetic conditions within their family require comprehensive
      services that address the medical and emotional aspects of disease. The use of
      these types of genetic services and testing can raise ethical and social
      concerns. Key components of the genetic counseling process and the complex issues
      that surround genetic information are discussed.

PMID- 10957678
TI  - Prenatal and neonatal testing and screening: a double-edged sword.
AB  - This article describes some of the more commonly requested prenatal and neonatal
      screenings and diagnostic tests. Additionally, it outlines the incidence and
      etiology of specific conditions followed by treatment and counseling options.
      Finally, issues regarding the ethics involved in testing are discussed. Practical
      recommendations and responsibilities for the nurse are interwoven throughout the
      article.

PMID- 10957680
TI  - Genetics and cardiovascular disease.
AB  - The traditional risk factors associated with the development of cardiovascular
      disease (CVD) account for approximately 50% of the variability in the risk for
      developing heart disease. Research in the genetic basis of CVD has helped
      scientists begin to quantify the nature of the additional unexplained variance.
      CVD may result from a variety of genetic causes, including single-gene mutations,
      the combined effect of more than one mutation, and the interaction of multiple
      genes and environmental factors. This article describes genetic influences on
      risk factors for CVD, discusses three genetic CVD disorders, and highlights
      recent developments in genetic therapy for the treatment of CVD.

PMID- 10957681
TI  - Breast cancer: genetics, risks, and strategies.
AB  - Breast cancer is the most common cause of cancer among women, with 175,000 new
      cases diagnosed in 1999. The recent discovery of inherited mutations on the BRCA1
      and BRCA2 genes and related research has increased our understanding of key risk
      factors. After identifying those who are at risk, health care providers must
      counsel women regarding appropriate prevention and early detection strategies.
      This article reviews the influence of genetics on breast cancer, identifies risk
      factors, discusses risk factor analysis, and suggests strategies for prevention
      and early detection of breast cancer.

PMID- 10957682
TI  - Hereditary colorectal cancer.
AB  - This article summarizes the genetics of colorectal cancer (CRC), a disease in
      which 15% to 20% of cases are inherited. Familial adenomatous polyposis and
      hereditary nonpolyposis CRC represent the two most common forms of inherited CRC.
      One particular mutation, APC11307K, is associated with CRC in certain Jewish
      populations. Inherited cancers can be prevented with careful attention to regular
      and frequent sigmoidoscopy or colonoscopy screening intervals and the prompt
      removal of premalignant polyps. The role of the nurse should include the prompt
      identification and referral of high-risk individuals. Ongoing patient and family
      counseling and education, multidisciplinary collaboration, support for primary
      prevention, and intensive screening are essential.

PMID- 10957683
TI  - The genetics of Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common cause of dementia in late life. AD has
      been described as early onset, occurring at or younger than age 50, or late
      onset, occurring at or older than age 70. Although AD is a genetically
      heterogeneous disorder, it is classified as familial or sporadic. Cases in which
      a clear pattern of inheritance within a family is established are termed familial
      Alzheimer disease (FAD). Sporadic, however, is problematic when studying a late
      onset disease such as AD. It is likely that people who may carry a mutation die
      of another cause before reaching the age of risk. This article describes the
      known genetic mutations resulting in an autosomal dominant pattern of inheritance
      in early onset AD and a polymorphism associated with the more common late onset
      disorder.

PMID- 10957679
TI  - Genetic testing and screening in pediatric populations.
AB  - It is conceivable that in the near future a family could present themselves to
      their health care provider and request to be tested for diseases X, Y, and Z,
      equipped only with a web page listing of disease-causing genes. The testing of
      children suggests subtle and controversial inherent conflicts, however. Decisions
      about whether to provide genetic testing become increasingly murky for a health
      care professional as the requests advance from testing a child for carrier status
      for an autosomal recessive disorder, to testing a girl for a sex-linked mutation,
      to testing an asymptomatic child for a susceptibility to a particular disorder.
      Although no single case can exemplify every variable and circumstance confronting
      health care professionals today, this case-based discussion of x-linked severe
      combined immune deficiency can serve as a framework to examine some of the
      potential dilemmas surrounding the testing of children for genetic disorders.

PMID- 10957684
TI  - Genetics of asthma and allergies.
AB  - This article is a literature review focusing on the underlying concepts of human
      genetics related to asthma and allergies. Asthma is classified as a complex
      genetic disorder with genetic susceptibility and an appropriate environmental
      stimulus necessary for the expression of disease. Intermediate phenotypes of
      asthma, which are used to study the disease, include the total IgE levels, the
      specific immune response, and end organ response. Because gene products cause the
      inflammation in asthma and allergies, the molecular cell biology of these events
      is reviewed. Although no one gene is implicated in causing asthma, candidate
      genes involved in the multiple phenotypic expressions of asthma are described.

PMID- 10957685
TI  - Hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is an autosomal recessive iron overload disorder
      that affects more than one million Americans. This underdiagnosed disorder is
      associated with high morbidity and mortality, which can be prevented with early
      identification and treatment. A DNA test that can identify asymptomatic at-risk
      individuals before biochemical indicators are positive is available commercially.
      Nurses need current knowledge about HH for two main reasons: (1) to ensure that
      at-risk individuals receive comprehensive information before genetic testing, and
      (2) to play a significant role in preventing chronic morbidity and premature
      death caused by HH.

PMID- 10957686
TI  - Legal issues associated with genetics.
AB  - With the evolution of genetic research, legal issues have emerged related to the
      health care delivery industry and the protection of patient information. The use
      of genetics or genetic enhancement expands the role of the nurse and also brings
      a new perspective to the nurse-patient relationship. Nurses now must discern
      their role in relation to patient privacy and confidentiality. In addition to
      reviewing the ethical and legal dilemmas of registered nurses in clinical
      practice, the nursing profession must review the level of responsibility
      appropriate when using genetic and or experimental treatments, especially when
      the nurse is not the primary care provider or the leader of the research team.
      Nurses will have to delve into privacy and confidentiality issues associated with
      genetic research. Although little case law exists on the relationship of nursing
      to genetic research and treatments, the implications of experimental research and
      policy associated with genetics must be analyzed to better understand their
      impact on the scope of nursing practice.

PMID- 10957688
TI  - Gene therapy.
AB  - Gene therapy represents a fundamentally new way to treat disease. Originally
      conceived as an approach to hereditary disease, it is now being applied to a
      broad range of acquired conditions such as infections, cancers, and degenerative
      disorders. A current overview of gene therapy is presented in this article,
      including descriptions of two clinical protocols and perspectives for new
      directions.

PMID- 10957687
TI  - Genetic discrimination in health insurance: an overview and analysis of the
      issues.
AB  - The problem of genetic discrimination in health insurance will increase as
      genetic knowledge expands and the number of genetic tests proliferates. Unless
      appropriate legislative protections are developed and enforced, a consequence of
      the genetic revolution may be that more people are put at risk for losing their
      health insurance. The current situation requires people to make difficult choices
      about taking tests that could save or prolong their lives. Unless these people
      believe that they and their families will be adequately protected from
      discrimination and from the possibility of losing or being denied health
      insurance, many will choose not to be tested for genetic conditions or
      predisposition to disease. Solutions to this problem require continuing research
      and debate and the creation of new policies and laws that protect the people
      while maintaining the economic viability of insurance companies. This article
      explores the problem of genetic discrimination as it relates to health insurance
      in the United States. The goal of this article is to assist nurses and other
      health care professionals to better understand the important and complex issues
      and concepts related to genetics, genetic testing, and genetic discrimination in
      health insurance.

PMID- 10957689
TI  - Comprehensive hypertension care in young urban black men: an example of a program
      of nursing research that integrates genetic science, clinical interventions, and
      patient outcomes.
AB  - Black Americans have the highest rate of hypertension in the world. The well
      known consequences of this condition include stroke, heart failure, and renal
      disease. The causes, care, and control of hypertension, especially among the
      underserved and understudied group of young urban black men, require more
      comprehensive models of health care delivery and an understanding of the gene
      gene and gene-environment interactions influencing blood pressure.

PMID- 10957690
TI  - Genetics in nursing education.
AB  - The discoveries stimulated by the human genome project have changed the way
      health and disease are thought about. In practice, health care professionals are
      responsible for the application of this knowledge. Guiding principles regarding
      genetics and health care lead to the knowledge nurses need, roles for nurses in
      relation to genetics, what knowledge is needed in nursing curricula, how to
      include the relevant information, and suggested approaches for inclusion despite
      barriers.

PMID- 10957692
TI  - Editorial

PMID- 10957691
TI  - Genetic resources: an annotated bibliography of internet and other resources.
AB  - The Internet has caused a major boom in the field of genetics. Internet use among
      the public and health care professionals continues to rise, but caution must be
      exercised when searching for information. This article presents some guidelines
      for determining good web sites, then follows with a compilation of Internet and
      other relevant genetics resources.

PMID- 10957693
TI  - Time to re-evaluate golden standards?

PMID- 10957694
TI  - Substance P.
AB  - Substance P is considered to be an important neuropeptide in nociceptive
      processes. Although substance P was described more than 60 years ago, there is
      still controversy about its exact role in nociception. This article reviews the
      current knowledge about the function of substance P in pain. Special emphasis is
      put on how to use this knowledge in the development of new ways to treat pain.

PMID- 10957695
TI  - The symptom check-list, SCL-90-R: its use and characteristics in chronic pain
      patients.
AB  - The SCL-90-R is a widely-used questionnaire for self-report of psychological
      distress and multiple aspects of psychopathology, as part of the evaluation of
      chronic pain patients and other non-psychiatric populations. The aim of this
      study is the presentation of clinical results of this multidimensional
      questionnaire in a convenience sample of 3540 chronic pain patients treated in a
      multidisciplinary pain centre. Confirmatory Factor Analysis (CFA), Exploratory
      Factor Analysis (EFA), single scale factor analyses and Cronbach's alphas are
      used to assess the internal structure and correlation to other instruments (CES
      D, STAI, MPSS) to assess construct validity. It is shown that the 9 dimensions
      postulated by Derogatis et al. (1977 a) cannot at all be distinguished in chronic
      pain patients. The use of single subscores of the SCL-90-R, often employed as a
      screening instrument for specific diagnoses, such as depression, is at least
      questionable in chronic pain patients.

PMID- 10957696
TI  - Psychological predictors of the effectiveness of radiofrequency lesioning of the
      cervical spinal dorsal ganglion (RF-DRG).
AB  - In this study, 54 patients suffering from chronic cervicobrachialgia (mean pain
      duration 7 years) were treated with radiofrequency lesioning of the cervical
      spinal dorsal root ganglion (RF-DRG). The aim of the study was to investigate
      whether psychological variables would be predictive for the changes in pain
      intensity after medical treatment. The following psychological aspects were
      measured: pain cognitions, negative self-efficacy and catastrophizing, physical
      and psychosocial dysfunction, and overall distress. The level of catastrophizing
      before treatment appeared to predict 10% of the changes in pain intensity after
      treatment. Changes in pain intensity after RF-DRG were positively correlated with
      changes in psychosocial dysfunction and negative self-efficacy.

PMID- 10957698
TI  - Pain and quality of life in patients with critical limb ischaemia: results of a
      randomized controlled multicentre study on the effect of spinal cord stimulation.
      ESES study group.
AB  - We carried out an assessment of pain and quality of life of patients with
      critical limb ischaemia during the follow-up of a multicentre randomized trial in
      more detail than previously reported. In a multicentre clinical trial 120
      patients were randomized between medical treatment and medical treatment plus
      spinal cord stimulation. Patients were selected on the basis of clinical symptoms
      and macrocirculatory data as described in the European consensus document on
      critical limb ischaemia. Data were collected at intake and then 1, 3, 6, 12 and
      18 months later. Primary outcome measures were limb salvage, pain relief and
      quality of life. Patient and limb survival was estimated with the Kaplan-Meier
      method. Pain was evaluated using the visual analogue scale (VAS), the McGill pain
      questionnaire, the pain score of the Nottingham Health Profile (NHP) and the use
      of analgesics. Quality of life was evaluated using the NHP, the EuroQol and
      mobility subscore of the Sickness Impact Profile. The 2-year limb survival was
      52% for SCS treatment and 46% for standard treatment (p =0.47). Pain relief was
      considerable in both treatment strategies (p<0.005) with no significant
      differences between the strategies. The improvement occurred within the first few
      months and remained stable during further follow-up. Patients with SCS used fewer
      non-narcotic and narcotic drugs (p<0.001 at t=1 and t=3, p<0.002 at t=6). The
      overall scores of quality of life improved significantly (p<0.05), with no
      difference in score between treatments. The subscores of mobility and energy of
      the NHP in non-amputated patients was significantly better in the SCS group
      (p<0.005). Amputation had a negative effect on mobility, resulting in a difficult
      rehabilitation but relieved pain substantially (p<0. 05). In contrast to the
      existing literature, the randomized trial revealed no major difference in overall
      pain and quality of life assessment between treatment groups. The effect on
      energy and mobility was significantly better in patients treated with SCS, who
      also used substantially fewer analgesics.

PMID- 10957697
TI  - Gender differences in regional brain response to visceral pressure in IBS
      patients.
AB  - In two experiments including a total of 30 irritable bowel syndrome patients,
      symptom-mimicking rectal pressure stimuli elicited changes in regional neural
      activation as measured by positron electron tomography (PET) cerebral blood flow
      images. Although most stimuli were not rated as painful, rectal pressure
      increased regional cerebral blood flow (rCBF) in areas commonly associated with
      somatic pain, including the anterior cingulate, insula, prefrontal cortex,
      thalamus, and cerebellum. Despite similar stimulus ratings in male and female
      patients, regional activations were much stronger for males. In both experiments,
      rectal pressure activated the insula bilaterally in males but not in females.
      Insula activation was associated most strongly with objective visceral pressure,
      whereas anterior cingulate activation was associated more with correlated ratings
      of subjective discomfort. The insula is discussed as a visceral sensory cortex.
      Several possible reasons for the insula gender effect are proposed.

PMID- 10957699
TI  - Low frequency TENS is less effective than high frequency TENS at reducing
      inflammation-induced hyperalgesia in morphine-tolerant rats.
AB  - Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly
      used for relief of pain. Extensive research has been done on the effectiveness of
      each of these two methods for pain relief when given independently. However, very
      little literature exists examining the effectiveness of their combined use.
      Systemically administered morphine activates mu opioid receptors and when
      administered for prolonged periods results in analgesic tolerance. Low (4 Hz) and
      high (100 Hz) frequency TENS activate mu- and delta-opioid receptors,
      respectively, It is thus possible that TENS would be less effective in morphine
      tolerant subjects. The current study investigated the effectiveness of high- and
      low-frequency TENS in the reversal of hyperalgesia in inflamed rats that were
      morphine-tolerant. Morphine tolerance was induced by subcutaneous implantation of
      morphine pellets over 10 days. Knee joint inflammation was induced by injection
      of kaolin and carrageenan into the knee joint cavity. Secondary heat hyperalgesia
      was tested by measuring the paw withdrawal latency to radiant heat (1) before
      pellet implantation (either morphine or placebo), (2) after pellet implantation
      and before inflammation, (3) after inflammation and (4) after TENS. Both high
      (100 Hz) and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary
      hyperalgesia in animals receiving placebo pellets. In contrast, the hyperalgesia
      in morphine-tolerant animals with knee joint inflammation was unaffected by low
      frequency TENS but fully reversed by high frequency TENS. These results suggest
      that patients who are tolerant to morphine may respond better to high frequency
      TENS than to low frequency TENS.

PMID- 10957701
TI  - No effect of preoperative paracetamol and codeine suppositories for pain after
      termination of pregnancies in general anaesthesia.
AB  - Outpatient surgery demands rapid recovery and satisfied patients. The purpose of
      the study was to investigate whether rectal premedication with paracetamol and
      codeine would reduce the need of rescue analgesics, reduce the postoperative pain
      experience and result in faster eligibility for discharge. Ninety pregnant
      patients scheduled for day-case surgery with evacuation of the uterine cavity
      were randomly assigned into two groups. The paracetamol and codeine group was
      given a suppository with 60 mg of codeine and 800 mg of paracetamol together with
      standard premedication of intramuscular midazolam 0.08 mg/kg. The placebo group
      was given a placebo suppository and midazolam. All patients underwent the
      surgical procedure under general anaesthesia with alfentanil 15 microg/kg and
      propofol 1.5-2 mg/kg. There were no statistically significant differences between
      the groups in the postoperative pain experience as judged by Visual Analogue
      Scale (VAS-scale), verbal scale or the need for rescue analgesic medication with
      ketobemidone. Most of the patients experienced little postoperative pain with
      more than 70% scoring less than 20 mm on a VAS-scale from 0-100 mm at any time
      during the postoperative period. The paracetamol and codeine patients were
      significantly more sleepy at 30 min postoperatively. There were no differences
      between the groups in postoperative nausea or vomiting and no difference in
      discharge eligibility. The use of pre-operative suppository with paracetamol 800
      mg and codeine 60 mg is unnecessary in this group of patients.

PMID- 10957700
TI  - Plasma levels after peroral and topical ibuprofen and effects upon low pH-induced
      cutaneous and muscle pain.
AB  - Cutaneous applications are gaining popularity in the treatment of cutaneous pain
      and of painful disorders in joints and muscle. The low pH-pain model in human
      skin has previously been able to demonstrate the effects of NSAIDs in dose
      dependent manner and to establish time-effect relationships. We examined the
      analgesic action of ibuprofen after cutaneous application and compared the
      effects with oral administration. The two studies (with n = 12 subjects each)
      were performed in a double-blind, randomized fashion with a 1-week cross-over
      interval. In study 1 volunteers received intradermal infusions with phosphate
      buffered saline solution of pH 5.2 and received either 800 mg ibuprofen per os
      and topical placebo, or 4 g of a 5% commercial ibuprofen gel topically applied
      and oral placebo capsules, respectively. In study 2 the same protocol was applied
      with painful intramuscular infusion of stronger, isotonic phosphate buffer (pH
      5.2). The flow rate of the pH-infusion was individually adjusted to induce pain
      with a magnitude of 20% on a visual analogue scale (ranging from 'no' (0%) to
      'unbearable pain' (100%)). Ibuprofen (S-, R-) plasma levels after oral
      administrations were measured with HPLC, and after topical applications, by gas
      chromatography combined with mass spectroscopy to determine plasma levels in the
      range of ng/ml. In the cutaneous model pain ratings decreased to zero after
      topical verum gel within 45 min of the observation period of 55 min. Pain
      reduction after peroral ibuprofen was of the same magnitude, but was achieved
      within only 30 min. In the muscle model, the commercial ibuprofen gel did not
      reduce the pain in the acidic muscle. The peroral ibuprofen was less effective in
      the muscle compared to the skin pain model, although there was a significant
      progressive pain reduction within 55 min. Reasons for the differential
      susceptibility of cutaneous vs muscular acidosis pain to ibuprofen remain to be
      established.

PMID- 10957702
TI  - Five easy pieces on evidence-based medicine.

PMID- 10957704
TI  - Bulletin board

PMID- 10957703
TI  - Re: Headley, PM "NMDA antagonists: unequal to the task or unequal to each other-
      or both?".

PMID- 10957705
TI  - Rabies control in Japan.
AB  - In 1957 Japan succeeded in eradicating rabies, which had been endemic since the
      18th century, due to the registration and confinement of family dogs, the
      elimination of stray dogs, and the compulsory vaccination of dogs. At present,
      however, vaccination coverage of family dogs is far lower than the required level
      of 70%. The facilities that are presently able to investigate rabies are limited
      in number. In addition, few medical institutions keep rabies vaccine in stock or
      offer postexposure vaccination to travelers bitten by animals in rabies endemic
      areas. Moreover, rabies immunoglobulin (RIG) cannot be given to such individuals
      because RIG is not produced at present in Japan, nor is it authorized to be
      imported. To keep Japan free from any rabies deaths, an improvement in
      vaccination coverage among dogs and in the supply of postexposure prophylaxis is
      required, and the establishment of a rabies surveillance system is also
      considered to be essential.

PMID- 10957706
TI  - A proposal for safety standards for human use of cholera toxin (or Escherichia
      coli heat-labile enterotoxin) derivatives as an adjuvant of nasal inactivated
      influenza vaccine.
AB  - Cholera toxin (CT) and Escherichia coli heat-labile toxin (LT) are not only the
      causative agents of diarrhea but are also strong mucosal adjuvants which enhance
      immune responses to mucosally coadministered bystander antigens. One of the most
      promising applications of these toxins would be as mucosal adjuvant of nasal
      influenza vaccine. In comparison to current inactivated vaccines, the nasal
      vaccine provides superior cross-protection by inducing production of cross
      reacting anti-viral IgA antibodies in the respiratory tract even when the vaccine
      strain is different from the epidemic strain. On the use of the toxins as mucosal
      adjuvants in humans, toxicity and allergenicity of the toxins are problems which
      impinge on safety. To resolve these problems, various approaches have been
      attempted to produce less toxic and less allergenic CT (or LT) derivatives. We
      now propose the following standards for human use of safer CT (or LT) derivatives
      as an adjuvant of a nasal influenza vaccine. Thus, CT (or LT) derivatives can be
      administered intranasally together with a current inactivated influenza vaccine,
      provided they meet the following criteria. 1) A single dose of the derivatives,
      administered intranasally by spraying, should be around 100 Eg/adult in a volume
      of less than 0.5 ml. 2) CT (or LT) derivatives should retain the properties of
      the native CT (or LT), i. e., the ability to augment secretory IgA and serum IgG
      Ab responses to viral surface glycoproteins, when administered intranasally
      together with an inactivated influenza vaccine. 3) CT (or LT) derivatives should
      not induce IgE Ab responses to the vaccine, as well as to the CT (or LT) itself.
      4) The CT (or LT) should be nontoxic; the toxicity of the derivatives, as
      determined by the Y-1 adrenal cell assay, should not exceed 1/100 EC(50) of the
      native CT (or 1/1000 ECi of the native CT). 5) CT (or LT) derivatives should not
      cause serious disease in guinea pigs when administered intranasally or
      intraperitoneally at the dose used in humans (around 100 Eg).

PMID- 10957707
TI  - The impact of housing structures on filarial infection.
AB  - A study was undertaken to correlate the impact of housing and patterns of house
      construction on the vector density and transmission of filaria among the
      inhabitants of these houses. Three different types of houses in ecologically
      similar hamlets of Hariharpur village in Varanasi were selected for determining
      the density of Culex quinquefasciatus, the vector of Wuchereria bancrofti and its
      infectivity. The maximum per man hour density of the vector was recorded during
      March (31.66, 40.33 and 41.33) while minimum was recorded during June (1.3, 2.6
      and 0.33) in all the three types of houses. Infection rate in the vectors
      collected from poorly constructed houses was observed during April, May, October
      and January of the following year, whereas in moderately constructed houses,
      infection was observed only in September and in the well constructed houses
      dissection results did not reveal any infection during the months of the study.
      Infectivity rate was observed to be 10.0% in moderately constructed houses (group
      B) during the month of September and 14.2% in poorly constructed houses (group C)
      during the month of October. Parasitological observations of the population
      showed a 12.2% microfilaria (mf) rate and 6.7% disease rate among the residents
      of poorly constructed houses, 5.8% mf rate and 2.9% disease rate among residents
      of moderately constructed houses. Among residents of well built houses (Group A),
      none were found to be positive with mf, but disease rate was observed to be 2.7%.
      Throughout the year the relative humidity was observed to be higher in the poorly
      constructed houses and ambient temperatures were found to be lower during the
      summer but higher during the winter than to those of the better constructed
      houses. The study made evident that the construction of houses plays an important
      role in the vector's resting preference, leading to a higher density in poorly
      constructed houses, thereby increasing the possibility of infection within them,
      and thus maintaining a higher potential for filarial transmission among its
      inhabitants.

PMID- 10957708
TI  - Inhibition of Aeromonas caviae and A. sobria by sodium choloride, citric acid,
      ascorbic acid, potassium sorbate and extracts of Thymus vulgaris.
AB  - The respective and combined effects of sodium chloride, ascorbic acid, citric
      acid, potassium sorbate, and Thymus vulgaris extract on the growth of Aeromonas
      caviae and Aeromonas sobria were investigated. Sodium chloride (3%) significantly
      reduced the growth and 4% NaCl inhibited growth of the tested strains. Ascorbic
      acid (0. 1%), potassium sorbate (0.05%), and citric acid (0.03%) slightly
      inhibited growth. T. vulgaris extract (0.3%) greatly reduced the growth. Various
      combinations of these compounds prevented growth of the tested strains. A
      combination of NaCl (3%) and ascorbic acid (0. 1%), citric acid (0.03%) and
      potassium sorbate (0.05%), or citric acid (0.03%) and ascorbic acid (0.1%)
      inhibited growth of A. caviae and A. sobria. In fish homogenates, the addition of
      ascorbic acid (0. 1%) and citric acid (0.03%) was the most effective combination
      tested.

PMID- 10957710
TI  - Workflow from clean to dirty, HACCP and inclusiveness principles in effective
      implementation of hospital infection control.

PMID- 10957709
TI  - Nationwide nucleic acid amplification testing of hepatitis B virus, hepatitis C
      virus and human immunodeficiency virus type 1 for blood transfusion and follow-up
      study of nucleic acid amplification positive donors.
AB  - This study described a program for and the results of a nationwide nucleic acid
      amplification testing (NAT) screening for hepatitis B virus (HBV), hepatitis C
      virus (HCV), and human immunodeficiency virus type 1 (HIV-1) by multiplex reagent
      with a pooled system. After routine serological screening, this test was used in
      order to be in time for blood transfusions. The Japanese Red Cross currently
      supplies donated blood all over Japan for blood transfusion. As of January 2000,
      2,140,207 units (5,093 pools) were tested by a pool size of 500 and 19 HBV DNA
      positive cases and 8 HCV RNA-positive cases were found. Since February 2000, the
      pool size was switched to 50 and among 420,770 units (8,564 pools), 7 HBV DNA
      positive cases and 1 HCV RNA-positive case were found. HIV RNA was not detected
      in any of the tested pools. Among the 26 HBV DNA positives, 22 were wild type; of
      these, 6 (23%) had hepatitis B surface antigen (HBsAg) that was undetectable by
      overnight enzyme immunoassay (EIA). Except for one case, in which coexisting
      antibody inhibited the immune reaction, all 17 cases that were followed later
      showed seroconversion. In 10 of these cases, HBV DNA disappeared below the level
      of detection and seroconversion of IgM anti-HBc and anti-HBc antibody occurred
      during the observation period. The remaining 4 cases were precore mutants and all
      had an undetectable level of HBsAg by EIA. Three cases did not show IgM anti-HBc
      seroconversion, which should be observed during the early stage of HBV infection.
      As for the HCV RNA, the following types were identified: 2 genotype II (1b), 3
      genotype III (2a), and 4 genotype IV (2b). A weak anti-HCV positive reaction was
      observed in two cases and strong seroconversion in one case among 4 of the cases
      that were followed. Although it is not 100%, NAT narrows the window period in
      early-stage infection, resulting in an exponential reduction of the virus load
      that escapes serological screening tests for blood destined for blood
      transfusions. In the case of HBV, NAT screening detects HBV DNA in persistently
      infected individuals with extremely low levels of HBV antigen and antibody often
      observed in the case of HBV mutants.

PMID- 10957711
TI  - Annual incidence of tsutsugamushi disease caused by different serotypes of
      Orientia tsutsugamushi in Miyazaki Prefecture in 1991-1999.

PMID- 10957712
TI  - Acute hepatitis outbreak in Tokyo caused by hepatitis A virus of common origin
      transmitted through oral and sexual routes.

PMID- 10957713
TI  - Epidemiological analysis of a methicillin-resistant Staphylococcus aureus
      outbreak in a neonatal intensive care unit after cleaning of environmental
      surfaces in the unit by genomic DNA fingerprinting using pulsed-field gel
      electrophoresis.

PMID- 10957714
TI  - Duration of echovirus 30 excretion in stools from patients with aseptic
      meningitis.

PMID- 10957715
TI  - Possible enhancement of GB virus C infection in cultured cells by addition of
      anti-E1 antibodies.

PMID- 10957716
TI  - A case of poliomyelitis associated with infection of wild poliovirus in Qinghai
      Province, China, in October 1999.

PMID- 10957717
TI  - Directions for biomedical research in alcohol and HIV: where are we now and where
      can we go?

PMID- 10957718
TI  - Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical
      significance and implications for resistance to protease inhibitors.
AB  - Amino acid substitutions at HIV-1 Gag p7/p1 and p1/p6 cleavage sites may be
      selected under antiretroviral pressure or represent natural polymorphisms.
      Whether changes are associated with specific protease (PR) mutation patterns and
      different clinical evolution has not been investigated. p7/p1 and p1/p6 cleavage
      site sequences from sera from 110 patients infected with HIV-1 were compared by
      regression analysis, using clinical, laboratory, and sequence variables, and the
      evolution of CD4(+) cell counts and viral load over time. Sixteen of 35 (46%)
      individuals naive to PR inhibitors (PIs), and 49 of 75 (65%) receiving PI
      containing regimens had a p7/p1 and/or p1/p6 cleavage site polymorphism (p =
      0.06). A431V and/or L449F were present exclusively among individuals failing PI
      treatment (17 of 75 [23%] and 3 of 75 [3%], respectively). There was a
      significant association between A431V and PR M46I,L (OR 13.7; 95% CI 4.2-44.3)
      and V82A,F,T (OR 8.8; 95% CI 2.7-27.8). Natural polymorphism P453L was strongly
      associated with the selection of PR I84V (OR 49.5; 95% CI 12-212) and selected
      against V82 mutation (OR 0.15; 95% CI 0.02-1. 2). After a median followup of 15
      months, no polymorphism was associated with parameters of disease progression
      among individuals failing treatment. Only a limited set of amino acid
      substitutions can be tolerated at p7/p1 and p1/p6 cleavage sites. A431V is
      selected in association with specific PR inhibitor mutations. Natural
      polymorphism P453L might direct the PR resistance pathway through I84V instead of
      V82 mutation. No short-term clinical impact of cleavage site substitutions was
      documented.

PMID- 10957719
TI  - Parallel decrease in neurotoxin quinolinic acid and soluble tumor necrosis factor
      receptor p75 in serum during highly active antiretroviral therapy of HIV type 1
      disease.
AB  - The chronic immune activation state in HIV disease leads to increased activity of
      the rate-limiting tryptophan-kynurenine pathway enzyme indoleamine 2,3
      dioxygenase (2,3-IDO), thereby increasing the formation of neurotoxic tryptophan
      metabolites such as kynurenine and quinolinic acid. We investigated whether
      highly active antiretroviral therapy (HAART) (median duration, 100 days; range,
      50-188 days) lowers serum levels of these metabolites in HIV-infected individuals
      and if so, whether this was paralleled by changes in a surrogate marker for
      immune activation, i.e., soluble tumor necrosis factor receptor p75 (sTNFR p75)
      concentrations. Baseline quinolinic acid (848 nM, 95% CI 567-1130 vs. 303 nM, 95%
      CI 267.1-339.5) and kynurenine (4.1 microM, 95% CI 3.3-4.9 vs. 2.7 microM, 95% CI
      2.4-2.9) concentrations as well as the mean kynurenine-to-tryptophan ratio
      (108.2, 95% CI 76.1-140.4 vs. 51.4, 95% CI 47.6-55.3) in 17 HIV-1-infected
      outpatients (7 with AIDS) were significantly higher than those in 55 healthy age
      matched controls (p < 0.01), respectively. Serum quinolinic acid concentrations
      in 14 of 17 patients decreased (mean, -44.4%) during HAART in comparison with
      baseline (471.2 nM, 95% CI 288-654.3; p = 0. 022). Thirteen of these 14 patients
      also had decreases in sTNFR p75 concentrations. Overall, the mean sTNFR p75
      concentration decreased by 36.3% (13.5 ng/ml, 95% CI 9.3-17.8 vs. 8.6 ng/ml, 95%
      CI 5.9-11. 4; p = 0.01, n = 17). Reduction in viral load through HAART and
      subsequent mitigation of the pathological immune activation state in HIV disease
      may have reduced 2,3-IDO over activation. This eventually led to a decrease in
      quinolinic acid formation. The parallel reduction of the immune activation marker
      sTNFR p75 supports this hypothesis.

PMID- 10957720
TI  - Genetic analysis of viral variants selected in transmission of human
      immunodeficiency viruses to newborns.
AB  - Our previous studies have indicated that HIV transmission from infected mothers
      to infants occurs with viruses showing rapid kinetics of replication, and either
      resistance to maternal neutralizing antibodies or sensitivity to enhancing
      antibodies. The genotypic patterns that result in these and other phenotypic
      viral characteristics may provide clues to the selection pressures exerted during
      this mode of transmission. For this reason, DNA sequences of the envelope gene
      (env) were determined for viral isolates obtained from seropositive women who
      were mothers of either infected or uninfected infants. Sequences of viruses
      isolated early in life from the infected newborns were also determined, such that
      diversity both within isolates and between maternal and infant isolates could be
      assessed. Among isolates obtained from mothers of uninfected infants, the V3
      region of env demonstrated a higher degree of heterogeneity than those from
      mothers of infected infants. Similar to the viruses obtained from the mothers of
      infected infants, the infant-derived viral sequences were relatively homogeneous.
      Finally, the reactivity of maternal plasma with infant-derived HIV isolates,
      whether via neutralizing or enhancing antibodies, appeared to predict the
      distribution of viral sequences in the infant isolates. These data suggest that
      selective pressure on HIV-1 during transmission or growth in the infected infant
      may be mediated by biologic and/or immunologic processes.

PMID- 10957721
TI  - Natural variation in the amino acid sequence around the HIV type 1 glycoprotein
      160 cleavage site and its effect on cleavability, subunit association, and
      membrane fusion.
AB  - To assess the natural variation of the structure of the cleavage site as well as
      the N-terminal region of gp41 for the cytopathogenicity of HIV-1, syncytium
      inducing (SI) and non-syncytium-inducing (NSI) virus isolates were obtained from
      HIV-1-infected patients. In addition, the coreceptor usage of the isolates was
      determined by infection of primary macrophages and PM-1 cells. DNA sequences
      encoding the C-terminal 41 amino acid residues of gp120 and the 64 amino acid N
      terminal residues of gp41 were amplified by the polymerase chain reaction and
      inserted into the Env expression vector pNLA1. When transfected into HeLa-T4(+)
      cells, all the recombinant plasmids, including those with inserts from NSI
      isolates, led to the formation of processed glycoprotein and to syncytium
      formation. One construct displayed significant lowered fusion capacity and had an
      amino acid exchange in the first position of the gp41 N terminus (gp41, 512A-->S)
      leading to a decreased association of the SU and TM subunits. Four constructs
      derived from two isolates of the same patient showed an unusual gp41 N terminus
      (gp41, 514G-->P) and a slightly diminished fusion capacity due to a decreased
      cleavability. This indicates that the major determinants for the SI and NSI
      phenotypes are not located around the gp160 cleavage site and that the N terminus
      of gp41 plays a minor role in the processing and fusion capacity of wild-type HIV
      1 isolates.

PMID- 10957722
TI  - Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain
      reaction to quantify SIV RNA load: comparison of one- versus two-enzyme systems.
AB  - Plasma viral RNA load is a key parameter in disease progression of lentiviral
      infections. To measure simian immunodeficiency virus (SIV) RNA loads, we have
      established a quantitative one-tube assay based on TaqMan chemistry. This real
      time reverse transcriptase-polymerase chain reaction (RT-PCR) has advantages
      compared with previous methods, such as higher sensitivity, shorter time
      consumption, and low risk of cross-contamination. The sensitivity of the assay
      was optimized by comparing different enzyme systems. The one-enzyme protocol
      using rTth DNA polymerase was superior to two assays employing two enzymes. It
      detects 100% of the samples containing four copies of RNA transcript and allows
      quantification of viral RNA loads over an 8-log unit dynamic range. As few as 50
      copies per milliliter of plasma can be detected within RNA extracted from 140
      microl of plasma. This is especially relevant in studies employing neonatal
      macaques, from which only small volumes of blood can be sampled, and in studies
      in which low viral RNA loads are expected. Because of the use of rTth DNA
      polymerase, DNA contamination can be avoided by carryover prevention with uracil
      N-glycosylase (UNG). We demonstrate that for optimization of real-time PCR
      sensitivity, not only concentrations of different reagents but also different
      enzyme systems must be evaluated. Our assay facilitates and enhances the
      quantification of plasma RNA loads, a critical parameter for many studies,
      including evaluations of vaccine candidates or antiviral regimens.

PMID- 10957723
TI  - Generation of monoclonal antibodies specifically directed against the proximal
      zinc finger of HIV type 1 NCp7.
AB  - The HIV-1 NCp7 contains two spatially close zinc fingers, required for the
      production of infectious particles. To investigate in more detail the function of
      the zinc finger domain, monoclonal antibodies were generated with a cyclic analog
      of the NCp7 proximal zinc finger. This analog was shown to bind zinc ions and to
      preserve the highly folded structure of the native peptide (Dong C-Z et al.: J Am
      Chem Soc 1995;117:2726-2731). We report here two monoclonal antibodies (2B10 and
      4D3), which are the first monoclonal antibodies directed against CCHC NCp7 zinc
      fingers. Dot-blot experiments revealed that a few nanograms of synthetic NCp7 can
      be detected on a nitrocellulose membrane. Whereas 2B10 appears specific for an
      epitope located in sequence 19-27 of NCp7, 4D3 appears to be structurally
      specific. Immunocomplex affinities were evaluated, using BIAcore technology, to
      be up to 1 and 10 nM, respectively, for 2B10 and 4D3 in 100 mM NaCl. These
      antibodies were able to recognize NCp7 in the Gag polyprotein precursor and were
      shown to immunoprecipitate NCp7 from a cell supernatant. Moreover, NCp7-Vpr
      interaction mediated by the zinc fingers is inhibited by 2B10, emphasizing the
      role of these domains in the protein-protein complex. These results indicate that
      2B10 and 4D3 behave as useful tools for studying both NC protein functions during
      the course of virion morphogenesis and the role played by its zinc finger domain
      at various steps in the retroviral life cycle.

PMID- 10957724
TI  - Immunogenic properties of reverse transcriptase of HIV type 1 assessed by DNA and
      protein immunization of rabbits.
AB  - Genetic immunization may be one way to prime individuals for a subsequent broad
      anti-HIV-1 immune response. Reverse transcriptase of HIV-1 (RT) presents a
      selective target for attempts to arrest replication of HIV-1. Rabbits immunized
      with a plasmid carrying the gene for reverse transcriptase HIV-1 (RT DNA)
      developed potent antibody and cellular responses to the gene product. The
      immunogenic properties of RT DNA and recombinant reverse transcriptase were
      compared in rabbits. The specific immune responses were similar to those reported
      previously for HIV-1 infected humans. The array of B and T cell epitopes
      recognized in RT DNA-immunized rabbits was broader than in rabbits immunized with
      the recombinant RT. We localized seven novel B and T cell epitopes and
      concordance between B cell and helper T cell epitopes was observed. B cell
      epitopes of RT induced proliferation of peripheral blood mononuclear cells and
      were active as helper T cell epitopes. T cell-proliferative responses to the
      epitopes of RT preceded or paralleled the production of antibodies of the same
      specificity. Subdomains of reverse transcriptase involved in the enzymatic
      activity of RT were highly immunogenic. Anti-RT IgG partially inhibited reverse
      transcription in vitro.

PMID- 10957725
TI  - Monoclonal antibodies to native HIV type 1 reverse transcriptase and their
      interaction with enzymes from different subtypes.
AB  - Recombinant reverse transcriptase (RT) from HIV-1 subtype B was used to produce
      mouse anti-RT monoclonal antibodies (MAbs). Immunization was done by mixing RT
      with the ISCOM matrix-forming adjuvant saponin (Quil A). Two different assays,
      both based on the interaction of native RT and antibodies, were used to monitor
      the immune response in mice and for screening, selection, and characterization of
      the MAbs. The first assay measures the capacity of antibodies to inhibit the
      polymerase activity of the RT and the second assay measures the ability of
      antibodies to capture enzymatically active RT. Twelve clones with the capacity to
      inhibit at least 50% of the RT activity and 34 clones with high RT-capturing
      capacity were found. The MAb panel was utilized to evaluate the immunological
      properties of 18 different RTs representing 9 different HIV1 subtypes. The RT
      inhibitory MAbs could be divided into two groups based on their pattern of cross
      reactivity toward the different HIV-1 RTs. The degree of diversity recorded among
      MAbs with RT-capturing capacity was larger. At least seven groups of MAbs with
      distinct cross-reactivity patterns were identified. Thus, the degree of isoenzyme
      specificity varied greatly, from MAbs that were quite specific for subtype B RT
      to one MAb that was able to capture the RTs from all HIV-1 isolates tested except
      one of the two group O isolates. In conclusion, our study revealed that there
      exist surprisingly large immunological differences between RTs from different HIV
      1 subtypes as well as from the same subtype.

PMID- 10957726
TI  - Simian-human immunodeficiency virus-associated nephropathy in macaques.
AB  - A number of chimeric simian-human immunodeficiency virus (SHIV) viruses
      containing tat, rev, vpu, and env from HIV-1 (strain HXBc2) in a genetic
      background of simian immunodeficiency virus (SIV(mac)239) have been derived from
      the parental nonpathogenic SHIV-4 virus. In this article we examine the renal
      pathology associated with the derivation of these pathogenic SHIV strains. The
      first of the pathogenic SHIVs, SHIV(KU-1), is associated with rapid CD4(+) T cell
      loss and opportunistic infections associated with AIDS, but only one of four
      infected pigtail macaques examined has developed significant renal pathology. The
      renal pathology in this macaque consists of a diffuse increase in matrix in the
      core of each lobule with collapsed glomerular capillries, which is similar to the
      renal changes reported in HIVAN. Passage of this virus into rhesus macaques
      yielded SHIV(KU-2), which results in renal pathology in three of four inoculated
      rhesus macaques in which <10% of the glomeruli are involved. A molecular clone of
      SHIV(KU-2) was derived (SHIV(KU-2MC4)) that causes neurologic and renal pathology
      with more than 60% of the glomeruli involved and results in uremic level BUN
      concentrations. These results indicate that SHIV(KU-2MC4) causes severe
      significant glomerular pathology and should permit a detailed analysis of the
      molecular determinants associated with the development of SHIV-associated
      glomerulosclerosis in rhesus macaques.

PMID- 10957727
TI  - Genetic variability of human immunodeficiency virus type 2 C2V3 region within and
      between individuals from Bissau, Guinea-Bissau, West Africa.
AB  - The V3 loop of both HIV-1 and HIV-2 is characterized by a high degree of genetic
      variation. To investigate the spectrum of HIV-2 variability in nature we have
      focused on the C2V3 region of Env and analyzed 108 viral sequences obtained from
      uncultured peripheral blood mononuclear cells obtained from 16 HIV-2-seropositive
      individuals from Bissau (Guinea-Bissau). The estimated values of genetic
      divergence between individuals were higher than those calculated from sequence
      information collected in a single individual. We have also found that the
      sequences surrounding the V3 loop contribute significantly to the overall genetic
      diversity of the C2V3 region of HIV-2 gp105, while the V3 loop itself seems to be
      rather conserved. Phylogenetic analysis demonstrated that all the individuals
      enrolled in this study were infected with HIV-2 subtype A viruses.

PMID- 10957731
TI  - The Australian health system.

PMID- 10957728
TI  - Evidence of the existence of a new circulating recombinant form of HIV type 1
      subtype A/J in Cameroon. The European Network on the Study of In Utero
      Transmission of HIV-1.
AB  - Several genetic subtypes and circulating recombinant forms (CRFs) of HIV-1 have
      been identified. The greatest degree of genetic diversity is displayed by
      variants from Central and West Africa. HIV-1 env C2-V5 and protease sequences
      were obtained from 15 HIV-1-infected pregnant women, who were selected from a
      larger cohort study in Yaounde, Cameroon. Fourteen of 15 virus variants were
      shown to be recombinant, whereas a single variant appeared to be nonrecombinant
      subtype A. Five viruses were subtype A/J recombinants, with env genes derived
      from subtype A and protease genes derived from subtype J. Seven viruses clustered
      with reference sequences for CRF02 AG(IbNG) in both the env and protease gene
      fragments, and were thus subtype A/G recombinants. Two variants displayed even
      more complex recombination patterns. Phylogenetic analyses indicated that the
      five subtype A/J recombinants might be the first representatives of a previously
      unrecognized CRF.

PMID- 10957729
TI  - Presence of diverse human immunodeficiency virus type 1 viral variants in
      Cameroon.
AB  - Phylogenetic analysis of the gp41 region of 123 HIV-1-seropositive specimens from
      Cameroon showed that 89 were subtype A (71% of these sequences were IbNg-like),
      12 (10%) were subtype D, 11 (9%) were subtype G, 5 (4%; closely related to
      subtype F2) were subtype F, 1 was subtype H, 2 (1.6%) remained unclassifiable,
      while 3 were group O. Further analysis of the two unclassifiable specimens in
      gag(p24), pol(prot), and env (C2V3 or gp41) showed that one (98CM19) was a
      complex mosaic between subtype A in p24 and subtype J prot, and unclassifiable in
      env (C2V3 or gp41). The second, 98CM63, clustered distinctly from all known
      subtypes in p24, prot, C2V3, or gp41. 98CM63 clustered with a specimen from
      Cyprus and these two geographically and epidemiologically unlinked specimens,
      with their distinct clustering pattern, may represent a new subcluster of subtype
      A. In conclusion, these findings confirm the high HIV-1 genetic variability and
      further suggest the continuous appearance of new viral strains in this
      population.

PMID- 10957730
TI  - Intelligent health systems and third millennium medicine in Australia.

PMID- 10957732
TI  - Teleradiology at the tertiary-level Women's and Children's Hospital in South
      Australia.
AB  - This article relates to a teleradiology trial undertaken in 1998-1999 at the
      Women's and Children's Hospital (WCH) in Adelaide, the capital of South
      Australia. The trial involved linking the hospital to a range of rural and remote
      sites in South Australia and the Northern Territory. The main aim of the project
      was to evaluate the advantages, limitations, benefits, and costs of a
      teleradiology service provided by WCH. The major finding from the study is that
      for a tertiary hospital providing second opinions in complex medical cases, a new
      form of business justification is required for teleradiology. The justification
      would include an emphasis on the range of high-level services that a
      subspecialist hospital such as the WCH can provide. The justification would also
      include the range of benefits to different parties, particularly the patient, and
      the intangible nature of many of the benefits.

PMID- 10957733
TI  - Evaluation of a telemedicine link between Darwin and Adelaide to facilitate
      cancer management.
AB  - The videoconferencing link between the Royal Adelaide Hospital Cancer Centre in
      South Australia and the Royal Darwin Hospital in the Northern Territory was
      established to allow Darwin clinicians to discuss cases in multidisciplinary
      oncology meetings at the tertiary referral center. This was evaluated by
      questionnaires distributed to the 20 health professionals involved and a group of
      8 patients with breast cancer whose case histories had been discussed via
      videoconferencing. All clinicians found the telemedicine link to be either useful
      or very useful in at least one aspect of their practice. The major benefit was
      cited as enabling remote area clinicians to participate in multidisciplinary
      cancer meetings. Three of the 5 remote clinicians who practiced solely in the
      Northern Territory found that the telemedicine consultation increased their
      workload, while only 2 of 13 clinicians who practiced solely in South Australia
      reported an increase over their normal activities, the others reporting no
      difference. Benefits identified included better support of isolated clinicians,
      decreased travel, and enhanced education and peer review. Perceived difficulties
      were technical problems, the impersonal nature of the interaction, inability to
      examine the remote patient and lack of reimbursement for the consultation. Seven
      of the eight patients surveyed were satisfied or very satisfied with the
      telemedicine consultation. Four patients wished to have access to videotape of
      the multidisciplinary meeting. Of those requiring travel for treatment, all
      believed that the telemedicine consultation influenced their care and shortened
      their time away from home.

PMID- 10957734
TI  - Telemedicine screening of diabetic retinopathy using a hand-held fundus camera.
AB  - The objective was to evaluate digital images of the retina from a handheld fundus
      camera (Nidek NM-100) for suitability in telemedicine screening of diabetic
      retinopathy. A handheld fundus camera (Nidek) and a standard fundus camera
      (Zeiss) were used to photograph 49 eyes from 25 consecutive patients attending
      our diabetic clinic. One patient had cataracts, making it impossible to get a
      quality image of one of the eyes (retina). The Nidek images were digitized,
      compressed, and stored in a Fujix DF-10M digitizer supplied with the camera. The
      digital images and the photographs were presented separately in a random order to
      three ophthalmologists. The quality of the images was ranked as good, acceptable
      or unacceptable for diabetic retinopathy diagnosis. The images were also
      evaluated for the presence of microaneurysms, blot hemorrhages, exudates, fibrous
      tissue, previous photocoagulation, and new vessel formation. kappa Values were
      computed for agreement between the photographs and digital images. Overall
      agreement between the photographs and digital images was poor (kappa < 0.30). On
      average, only 24% of the digital images were graded as being good quality and 56%
      as having an acceptable quality. However, 93% of the photographs were graded as
      good-quality images for diagnosis. The results indicate that the digital images
      from the handheld fundus camera may not be suitable for diagnosis of diabetic
      retinopathy. The images shown on the liquid crystal display (LCD) screen of the
      camera were of good quality. However, the images produced by the digitizer (Fujix
      DF-10M) attached to the camera were not as good as the images shown on the LCD
      screen. A better digitizing system may produce better quality images from the
      Nidek camera.

PMID- 10957735
TI  - Supporting communication in rehabilitation engineering teams.
AB  - The objectives of this project were to examine how members of a colocated
      rehabilitation engineering team communicate during their work and hence deduce
      the implications of these communications for the design of video-based
      technologies to support communication among members of a virtual rehabilitation
      engineering team. Twenty-four assessment clinic sessions conducted by
      rehabilitation engineering team were recorded on videotape over a period of 3
      years. These tapes were analyzed in considerable detail using a schema to
      identify and classify the talk and actions of the team members. Combining talk
      and actions with artifacts is a mechanism used by designers to develop ideas and
      communicate them to others. Speakers rely on actions to support and make their
      talk lucid. Cooperation based on sharing artifacts is a strength of face-to-face
      interaction. Participants can experience artifacts and observe others using the
      artifacts. Tools such as videoconferencing to support virtual rehabilitation
      teams will have to provide the participants with the ability to see often quite
      subtle gestures and actions if they are to grasp the meaning of the talk.
      Increased understanding how a team communicates visually complex data may (1) aid
      development of next generation videoconferencing equipment to better support
      distributed designers and rehabilitation engineers and (2) guide development of
      techniques to enhance the quality of visual data presentation in current
      videoconferencing systems.

PMID- 10957736
TI  - Clinical value of real-time tertiary fetal ultrasound consultation by
      telemedicine: preliminary evaluation.
AB  - Congenital fetal abnormalities are major causes of perinatal mortality and
      morbidity. The performance of ultrasound in the diagnosis and assessment of fetal
      anomalies varies enormously between tertiary referral centers and general units.
      Telemedicine offers a chance for tertiary realtime ultrasound consultations using
      standard telephone lines for remote sites. Preliminary investigations by our
      group have shown that real-time transmission of fetal ultrasound images over long
      distances via telephone (integrated systems digital network [ISDN]) lines is
      technically feasible. A live link of up to 2 Mb/s was established between Mater
      Mothers Hospital in Brisbane and Kirwan Hospital for Women in Townsville, which
      are 1,500 km apart. The objective of the current study was to evaluate the
      clinical value of a tertiary teleultrasound consultation service. Patients
      requiring tertiary ultrasound consultations were recruited from North Queensland.
      Clinicians from the referral site established an initial diagnosis and management
      plan. Using standard ISDN lines, the real-time ultrasound images were transmitted
      to the maternal fetal medicine subspecialists in Brisbane. The ultrasound
      examination was completed under the direction of the subspecialist. The
      subspecialist explained the findings to the patient at the end of the session,
      and discussed the diagnosis and management plans with the clinicians involved.
      Any diagnosis and management variations were classified into minor and major upon
      agreement by the two teams of clinicians involved. The clinicians and patients in
      Townsville rated the value of the consultation, and the subspecialists rated the
      confidence of their diagnoses on five-point scales. Pregnancy outcomes were
      obtained and the data analyzed. Over a 3-month period, 24 teleultrasound
      consultations were carried out. The indications for referral were: assessment of
      growth restriction/fetal wellbeing in the third trimester (6); detailed
      assessment for high-risk patients (5); evaluation of markers for anomalies (5);
      isolated fetal anomalies (1); and complex fetal problems such as twin/twin
      transfusion, multiple anomalies, etc. (7). Overall, the consultations resulted in
      some modifications to the clinical diagnosis in 45.8% of the cases, and
      modifications to the management plan in 33.3% of the cases (about half of which
      were minor variations). The clinicians rated the teleconsultations highly (mean
      rating 4.7, SD 0.44). The patients also rated the consultations highly, and were
      comfortable that their privacy and confidentiality were maintained during the
      consultation. The subspecialists were confident in making their diagnoses by
      telemedicine (mean score for confidence 4.2, SD 0.43). All the pregnancies have
      now been completed, with all antenatal diagnoses confirmed to be correct
      postnatally. Tertiary real-time ultrasound consultation by telemedicine is not
      only technically feasible, it is welcomed by the clinicians and patients
      involved. It also contributes to diagnostic and management differences. Larger
      scale clinical trials are needed to evaluate the true benefits and costs
      involved. The social benefits in bridging the healthcare gap between the country
      and the city, and in enabling patients in remote areas to stay close to their
      family under times of stress is well recognized by all involved.

PMID- 10957737
TI  - Case-based support in a cooperative medical diagnosis environment.
AB  - Many medical services are often not available to people living in remote areas
      because of the lack of medical specialists. This problem would be alleviated if a
      suitable environment was designed to allow physicians to collaborate and exchange
      ideas with centrally located medical specialists. This article describes an
      ongoing research project to design and implement a collaborative multimedia
      environment to allow medical specialists to cooperate in diagnosis. The
      environment will support remote database access for medical images, the retrieval
      of relevant medical cases to support diagnosis, and communication among
      participants through telepointers and image annotation by free-hand drawing.

PMID- 10957738
TI  - Three novel lossless image compression schemes for medical image archiving and
      telemedicine.
AB  - In this article, three novel lossless image compression schemes, hybrid
      predictive/vector quantization lossless image coding (HPVQ), shape-adaptive
      differential pulse code modulation (DPCM) (SADPCM), and shape-VQ-based hybrid
      ADPCM/DCT (ADPCMDCT) are introduced. All are based on the lossy coder, VQ.
      However, VQ is used in these new schemes as a tool to improve the decorrelation
      efficiency of those traditional lossless predictive coders such as DPCM, adaptive
      DPCM (ADPCM), and multiplicative autoregressive coding (MAR). A new kind of VQ,
      shape-VQ, is also introduced in this article. It provides predictive coders
      useful information regarding the shape characters of image block. These enhance
      the performance of predictive coders in the context of lossless coding.
      Simulation results of the proposed coders applied in lossless medical image
      compression are presented. Some leading lossless techniques such as DPCM,
      hierarchical interfold (HINT), CALIC, and the standard lossless JPEG are included
      in the tests. Promising results show that all these three methods are good
      candidates for lossless medical image compression.

PMID- 10957739
TI  - Delivery and interactive processing of visual data for a cooperative telemedicine
      environment.
AB  - Cooperative telemedicine environments are required for many situations such as
      consultations between residents and senior doctors, case correlations, and for
      teaching and research purposes. The mode of collaboration may vary with different
      situations, in terms of the synchronisation of tasks, the sharing of data and the
      extent of collaboration among participants. It is essential for participants to
      be able to remotely view and manipulate visual data (images, two-dimensional and
      three-dimensional graphics, animation, and video) as well as interactively run
      application programs that involve visual data in real-time. However, this is not
      possible with current network bandwidth limitations when large amount of visual
      data are involved. In this article, we first provide an analysis of functional
      requirements by participants in cooperative diagnosis in different types of
      situations, before discussing technical requirements, which form the basis for
      our system architecture design. A new approach is also presented for efficient
      handling of programs, which involve visual data in real time. This is achieved
      via the construction and transmission of small messages that encapsulate the
      operations in a pipelined or hierarchical fashion.

PMID- 10957740
TI  - Multipoint videoconferencing in health: a review of three years' experience in
      Queensland, Australia.
AB  - The objective was to review multipoint videoconferencing in Queensland Health
      from July 1996 to June 1999. Most videoconferencing has been conducted using
      desktop systems connected by integrated systems digital network (ISDN) at 128
      kbps. Data on utilization and problems were extracted from monthly reports and a
      survey was conducted. Multipoint videoconferencing increased steadily over the 3
      years from just and handful of conferences per month to 101 conferences and 703
      hours of bridge use per month. Primary uses were education and administration.
      Relatively few technical failures and operator errors were recorded. But by 1999,
      late connection and low attendance were major problems. Survey responses
      indicated that multipoint videoconferencing met expectations at the great
      majority of sites. Most respondents were satisfied with the level of
      administrative and technical support provided. In this large and decentralized
      state, multipoint videoconferencing has proven a useful and effective means of
      bringing healthcare workers together for a common purpose, supplementing face-to
      face events and other encounters mediated by communications technology such as
      satellite broadcasts and audioconferences.

PMID- 10957741
TI  - Building the Hospital Without Walls--a CSIRO home telecare initiative.
AB  - Aging populations and rising health costs have created the need to care for more
      patients in their own homes. Australia's Commonwealth Scientific and Industrial
      Research Organization (CSIRO) is developing a project, Hospital Without Walls,
      which aims to provide continuous monitoring of patients in certain diagnostic
      categories. The key technology is a miniature, wearable, low-power radio that can
      transmit vital sign and activity information to a home computer, from which data
      may be sent by telephone line and the Internet to appropriate medical
      professionals. The initial clinical scenario for this work is monitoring of
      elderly patients who have presented to hospitals following repeated falls.
      Accelerometers built into the radio sets will monitor activity and detect and
      characterise falls. Simultaneous measurement of heart rate will provide
      information about abnormalities of cardiovascular physiology at the time of a
      fall. The system has been tested in laboratory conditions and is being adapted
      for initial clinical trials.

PMID- 10957743
TI  - Additional Abstract from the American Telemedicine Association's Fifth Annual
      Meeting May 21-24, 2000, Phoenix, Arizona.

PMID- 10957742
TI  - A methodology for the development of software agent based interoperable
      telemedicine systems: a tele-electrocardiography perspective.
AB  - Telemedicine involves the integration of information, human-machine, and
      healthcare technologies. Because different modalities of patient care require
      applications running on heterogeneous computing environment, software
      interoperability is a major issue in telemedicine. Software agent technology
      provides a range of promising techniques to solve this problem. This article
      discusses the development of a methodology for the design of interoperable
      telemedicine systems (illustrated with a tele-electrocardiography application).
      Software interoperability between different applications can be modeled at
      different levels of abstraction such as physical interoperability, data-type
      interoperability, specification-level interoperability, and semantic
      interoperability. Software agents address the issue of software interoperability
      at semantic level. A popular object-oriented software development methodology -
      unified modeling language (UML) - has been used for this development. This
      research has demonstrated the feasibility of the development of agent-based
      interoperable telemedicine systems. More research is needed before widespread
      deployment of such systems can take place.

PMID- 10957744
TI  - Gender differences in addiction and recovery.

PMID- 10957745
TI  - Bulletin board

PMID- 10957746
TI  - HIV/STD risk reduction interventions in prison settings.

PMID- 10957747
TI  - Toward optimal health: the experts discuss lupus.

PMID- 10957748
TI  - Alendronate in the treatment of osteoporosis: a review of the clinical trials.
AB  - Osteoporosis is a highly prevalent disease. More than half of postmenopausal
      women will experience fractures. Women at high risk (osteoporosis as measured by
      bone density, low trauma fractures of any type, or certain other risk factors)
      often require pharmacological therapy. However, surveys show that most women who
      have recently had fractures are currently not being treated. Recent results from
      the first megatrial of osteoporosis with >6400 participants, the Fracture
      Intervention Trial (FIT), have provided important advances in our understanding
      of osteoporosis and the efficacy of alendronate. The FIT study and other large
      clinical trials show that alendronate effectively increases bone density, reduces
      the risk of hip and vertebral fractures by approximately half within the first 12
      18 months, and, most importantly, reduces the health consequences of fractures.
      Alendronate is also effective for preventing bone loss in early postmenopausal
      women. Thus, alendronate represents an important option for preventing and
      treating this common and debilitating disease. This article summarizes the wealth
      of data from FIT and other studies of alendronate in the context of the burden of
      illness associated with osteoporosis.

PMID- 10957749
TI  - Moderate alcohol consumption and changes in postprandial lipoproteins of
      premenopausal and postmenopausal women: a diet-controlled, randomized
      intervention study.
AB  - Moderate alcohol consumption is associated with a reduced risk of coronary heart
      disease. Earlier studies in men have shown that moderate alcohol consumption
      affects lipoprotein metabolism and hemostasis. In this diet-controlled,
      randomized, crossover trial, we investigated the effect on lipoprotein metabolism
      of moderate consumption of red wine or red grape juice with evening dinner for 3
      weeks in premenopausal women using oral contraceptives and in postmenopausal
      women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19
      hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride
      concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked
      3 hours after dinner with wine in both premenopausal and postmenopausal women.
      After wine consumption, the overall high-density lipoprotein (HDL) cholesterol
      level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p
      = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was
      reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as
      compared with grape juice consumption. The findings suggest that postprandial
      lipoprotein metabolism after moderate alcohol consumption differs between oral
      contraceptive-using premenopausal women and postmenopausal women. The response of
      postmenopausal women to alcohol resembled the response found in earlier studies
      in men.

PMID- 10957750
TI  - Examining the influence of gender on medical students' decision making.
AB  - Gender bias, described among practicing physicians, has rarely been examined in
      medical students. The current study examined the influence of gender bias on
      medical students' clinical decision making. We experimentally manipulated patient
      gender in 27 written clinical vignettes embedded in the United States Medical
      Licensing Examination (USMLE) Step 2 examination (a multiple-choice test of
      clinical decision making). Female and male patient versions of selected test
      cases were created within three categories: (1) diseases with previously
      established evidence of gender bias in the diagnosis or management of the
      disease, (2) diseases with a higher prevalence in a specific gender, and (3)
      diseases with similar prevalence in both genders and without evidence of gender
      bias in the literature. Among the 3059 students who wrote the USMLE Step 2
      examination in August 1998, there were small but significant differences in
      performance on the 12 gender bias cases. Students performed worse for the female
      patient version of the cases compared with the male patient version of the cases
      (mean of 55.8% correct for female cases compared with 57.7% correct for male
      cases) (p < 0. 01). Our data suggest that students were variably influenced by
      gender bias in their investigation and management of patients in a written test
      of clinical decision making.

PMID- 10957751
TI  - A conceptual model for the recruitment of diverse women into research studies.
AB  - Researchers' understanding of recruitment and retention of study subjects is in
      its infancy. To address the dearth of information on the underrepresentation of
      diverse populations of women in research studies relating to health issues, the
      University of California, San Francisco (UCSF) National Center of Excellence in
      Women's Health completed a comprehensive examination of issues related to
      recruitment. By synthesizing data from literature reviews, focus groups, surveys,
      one-on-one interviews, and direct experience recruiting diverse populations of
      women for research, a conceptual model was developed. This model outlines the
      interplay of three factors found to be relevant to the recruitment of diverse
      populations of women into research studies: awareness, acceptance, and access.
      Practical examples of cost-effective recruitment strategies to be considered for
      implementation to increase the presence of awareness, acceptability, and access
      are included in this report.

PMID- 10957752
TI  - Postmenopausal hormone use following a 3-year randomized clinical trial.
AB  - Postmenopausal women often discontinue estrogen therapy within the first year. No
      studies have examined reasons why women continue or discontinue hormone
      replacement therapy (HRT) after several years of use, when hormone side effects
      have subsided. We wanted to identify determinants of estrogen use after
      participation in a 3-year randomized placebo-controlled trial. The Postmenopausal
      Estrogen/Progestin Intervention (PEPI) study compared the effects of estrogen
      alone or in combination with one of three progestogens with placebo. Post-PEPI
      use of hormone therapy was ascertained 1-4 years after the trial in 775 (90%) of
      the originally enrolled women. Potential correlates of treatment decisions were
      identified from sociodemographic characteristics, medical histories, and clinical
      measures ascertained at baseline and during and after the trial. Among women who
      had been assigned to placebo during PEPI, post-PEPI hormone use was significantly
      less common in women who were adherent to placebo during PEPI, older, or of non
      Caucasian ethnicity. Hormone use was positively associated with hysterectomy.
      Among women assigned to an active regimen during PEPI, post-PEPI hormone use was
      significantly more common in women who used hormones before PEPI and in women who
      were adherent to hormones during PEPI. Older age, less education, and being non
      Caucasian predicted less hormone use. Post-PEPI hormone use was highest in San
      Diego and lowest in Iowa City. Women on placebo who lost more bone mineral
      density (BMD) were more likely to begin hormones than women with less bone loss.
      Lipids, blood pressure, and other cardiovascular risk factors had relatively
      little influence on hormone use. The main predictors of post-PEPI hormone use
      were those associated with use in the general population (education, ethnicity,
      geographical region, hysterectomy, and prior use/adherence).

PMID- 10957754
TI  - Gender and patient satisfaction with primary care: tuning in to women in quality
      measurement.
AB  - This study analyzes the relationship between patient gender and satisfaction with
      primary care visits, using 1999 survey data on 1691 women and 760 men making
      primary care visits at multiple sites affiliated with a large academic health
      system designated as a National Center of Excellence in Women's Health (COE). The
      main findings are that in multivariate analyses controlling for patient and visit
      characteristics, different aspects of the content of primary care visits are
      important to women and men. Women's overall satisfaction with visits is more
      dependent than men's on informational content, continuity of care, and
      multidisciplinarity. Men's overall satisfaction is more dependent on the personal
      interest shown in them by providers. No differences in satisfaction are found
      between those seen in sites affiliated with the COE and other primary care sites
      within the health system that are not core sites of the COE. We conclude that
      quality improvement and research in women's primary care could benefit from
      gender analysis of patient satisfaction data and from more gender-sensitive
      patient satisfaction measures.

PMID- 10957753
TI  - Sexual behaviors and other risk factors for Candida vulvovaginitis.
AB  - Sexual behaviors are associated with many genital infections, but the role of
      sexual variables as risk factors for Candida vulvovaginitis has not been clearly
      determined. To assess the association between sexual behaviors and other risk
      factors with the presence of Candida vulvovaginitis, we performed a case-control
      study comparing these potential risk factors in women with and without culture
      documented Candida vulvovaginitis in two Midwestern community-based medical
      offices. Participants included 156 women with Candida vulvovaginitis and 92
      controls, ages 18-60. Risk factors for Candida vulvovaginitis, including sexual
      and partnership behaviors, demographic data, past genital infections, exposures,
      and diet, were investigated using logistic regression. The presence of Candida
      vulvovaginitis was positively associated with recent cunnilingus (odds ratio [OR]
      = 2.22 for five times a month compared with no times, 95% confidence interval
      [CI] 1.36, 3.84), but was less likely in women who masturbated with saliva in the
      previous month (OR = 0.30 if masturbated five times vs. no times, 95% CI 0.09,
      0.99). Other independent risk factors included knowing the sexual partner a
      shorter period of time (OR = 1.56 for 1 year vs. 5 years, 95% CI 1.16, 2.13) and
      lower milk ingestion (OR = 3.57 for no servings vs. two servings per day, 95% CI
      2.00, 6.67). Increased number of sexual partners, early age at first intercourse,
      and increased frequency of intercourse are not related to risk.

PMID- 10957755
TI  - Meeting the needs of rural breast cancer survivors: what still needs to be done?
AB  - As screening and treatment for breast cancer improve, learning about survivors'
      post-treatment needs becomes increasingly important. Focus groups (n = 23) were
      conducted with breast cancer survivors (n = 128) in rural Washington communities
      during a 5-month period in 1996 to explore ways to improve the lives of rural
      breast cancer survivors and to expand existing knowledge of breast cancer
      survivorship. Survivors reported positive and negative outcomes of their cancer
      experience. Results indicate that the needs of many women with breast cancer,
      particularly women diagnosed with late-stage disease, are not being met.
      Participants diagnosed with late-stage cancer were more likely than participants
      diagnosed with early-stage cancer to comment about being treated poorly by the
      medical system and to voice a need for increased support and educational services
      for breast cancer patients. Rural survivors, regardless of stage at diagnosis,
      reported needing more education about breast cancer and more emotional support
      after diagnosis. Further efforts to facilitate support and education within the
      context of medical care and to improve patient-clinician relationships are
      needed.

PMID- 10957756
TI  - A study on maternal mortality in Mexico through a qualitative approach.
AB  - This report presents the main qualitative results of a verbal autopsy study
      carried out in three states of Mexico, which aimed at identifying the factors
      associated with maternal mortality that could be subject to modifications through
      concrete interventions. By reviewing death certificates issued in 1995, it was
      possible to identify 164 households where a maternal death had occurred. One
      hundred forty-five of these households were visited, and a precoded questionnaire
      was completed to explore socioeconomic and living conditions, as well as causes
      of death. An open-ended question to prompt the relatives to narrate all the facts
      that led to the maternal deaths was included in the questionnaire. This study
      presents an analysis of that question, focusing on the delays in the care-seeking
      process and organized according to the model of the three delays: in deciding to
      seek care, in reaching a care facility, and in actually receiving care after
      arrival. Additionally, problems related to quality of care are examined. For
      analysis of the accounts, structural, interactional/community, and subjective
      variables were identified that allowed refining of our understanding of the
      problem of maternal deaths. Finally, based on the findings of the study, this
      article presents a series of recommendations, highlighting that interventions
      should address the early stages of a complication and focus on decreasing the
      various forms of inequality (gender and socioeconomic) associated with the
      occurrence of maternal deaths.

PMID- 10957757
TI  - Women's health LiteratureWatch

PMID- 10957758
TI  - Corrigendum

PMID- 10957759
TI  - IL-12 in lung diseases.

PMID- 10957760
TI  - New treatments of ANCA-associated vasculitis.
AB  - The ANCA-associated systemic vasculides are, in many cases, life-threatening
      conditions. Combined treatment with corticosteroids and cyclophosphamide has
      improved their prognosis considerably. Five year survival does, however, still
      not exceed 75%, due to the occurrence of treatment resistant cases and the severe
      adverse effects of this treatment regimen. In this review new treatment
      modalities are discussed. In cases resistant to conventional therapy high dose
      intravenous immunoglobulin and T-cell directed biologicals, that is anti
      thymocyte globulin (ATG) and humanised monoclonal antibodies to CD4 and CDw52,
      may be effective. Also, TNF-directed treatment is being used. Less severe cases
      may benefit from methotrexate treatment instead of cyclophosphamide. For
      maintenance of remission azathioprine has been proven to be as effective as
      cyclophosphamide so preventing the toxicity of long-term cyclophosphamide
      treatment. Relapses may also be prevented by treatment based on changes in ANCA
      titers or by elimination of Staphylococcus aureus carriage which is associated
      with relapsing disease in Wegener's Granulomatosis. Several of those new
      treatment modalities are now being tested in controlled studies by the European
      Vasculitis Study Group (EUVAS).

PMID- 10957761
TI  - Mechanisms of defence in the lung: lessons from Pneumocystis carinii pneumonia.
AB  - Pneumocystis carinii continues to represent an important complication of
      individuals with compromised immunity. P. carinii interacts with immune and non
      immune cells in the lung and mediates lung injury through a variety of
      mechanisms. CD4+ T lymphocytes are the cornerstone in defence against P. carinii.
      Recent studies indicate that alveolar macrophages provide essential functions
      that significantly enhance clearance of P. carinii infection. P. carinii also
      attaches to alveolar epithelial cells, causing inhibition of epithelial growth
      and replication. In addition to cellular interactions, P. carinii organisms bind
      to a variety of host adhesive proteins present in the lower respiratory tract.
      Binding of these proteins to P. carinii modulates host cell recognition and
      immune responses to the parasite. During the course of P. carinii pneumonia,
      several inflammatory mediators are produced in the lung. Although necessary for
      control of infection, exuberant inflammatory responses also predispose the host
      to the development of acute lung injury. Thus, host defences against P. carinii
      depend on complex interactions between immune and non-immune cells as well as
      several mediators that facilitate host recognition and eventual elimination of
      infection. Understanding these complex processes may enable development of novel
      therapeutic approaches for management of this important infection.

PMID- 10957762
TI  - Calcium oxalate and iron accumulation in sarcoidosis.
AB  - BACKGROUND: In many patients with sarcoidosis, the granulomas contain inclusion
      bodies within giant cells. Many giant cells contain crystalline oxalate that
      chemically coordinates iron on the surface of the crystal. If this iron is
      incompletely coordinated and capable of redox cycling, then oxalate might
      contribute to granuloma formation in the lung. METHODS: Using human tissues,
      isolated alveolar macrophages and respiratory epithelial cells, we measured the
      ability of calcium oxalate to sequester iron, stimulate cytokine release and
      cause granuloma formation. We then studied the effects of in vivo oxalate
      instillation on pulmonary granuloma formation over 3 to 6 months in rats.
      RESULTS: Calcium oxalate present in human sarcoid granulomas sequesters
      significant amounts of iron and ferritin. In alveolar macrophage cultures,
      oxalate accumulates iron and stimulates ferritin production and giant cell
      formation. In cultured respiratory epithelial cells, calcium oxalate increases
      the release of two interleukins (IL), IL-8 and IL-6, involved in granuloma
      formation by 8 to 10 fold within 24 hours. Intratracheal instillation of calcium
      oxalate crystals into the lungs of rats is associated with pulmonary iron and
      ferritin accumulation and organic carbonyl formation consistent with sustained
      oxidative stress. These exposures were accompanied by influx of alveolar
      macrophages, giant cell formation, and a granulomatous response in the lung.
      CONCLUSIONS: These results support an association between calcium oxalate
      deposition in the lung, iron mediated oxidative stress and formation of some of
      the granulomas of sarcoidosis.

PMID- 10957763
TI  - Enhanced mRNA expression of Th1 cytokines and IL-12 in active pulmonary
      sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: Active sarcoidosis is considered to be a Th1
      dominant condition. We examined whether Th1 cytokines are highly expressed at
      inflammed lesions of Japanese patients with sarcoidosis. METHODS: To investigate
      the mRNA expression of Th1 cytokines and IL-12 in sarcoid BAL cells, we used
      semiquantitative reverse transcription--polymerase chain reaction method.
      RESULTS: The mRNA expressions of Th1 cytokines (IFN-gamma and IL-2) in active
      sarcoid BAL cells were significantly elevated as compared with those in healthy
      volunteers. The proportion of positive IL-4 mRNA expression in sarcoid BAL cells
      was not significantly higher than that in healthy volunteers. Further, there was
      no significant difference in IFN-gamma mRNA levels between the groups positive
      and negative for IL-4 mRNA expression. Although the proportion of positive
      expression of IL-12 mRNA in active sarcoid BAL cells was not significantly higher
      than that in healthy volunteers, the group positive for IL-12 mRNA expression had
      significantly elevated levels of IFN-gamma mRNA than did the negative group.
      CONCLUSIONS: These results may indicate that IL-12 induces IFN-gamma expression
      and subsequent Th1 dominant condition in Japanese patients with sarcoidosis.

PMID- 10957764
TI  - The prognosis of pulmonary sarcoidosis in Finland and Hokkaido, Japan. A
      comparative five-year study of biopsy-proven cases.
AB  - BACKGROUND AND AIM OF THE STUDY: The frequency and clinical picture of
      sarcoidosis are different in Finland and Hokkaido, Japan. The aim of this study
      was to compare the normalisation rate of chest radiographic changes in patients
      with biopsy-proven sarcoidosis. METHOD: The chest radiographs of 437 Finnish and
      457 Japanese patients were used and, for the purpose of this study, double
      checked in order to make sure that the interpretations were identical. On a
      yearly basis the radiographs were classified as normalised, improved, unchanged
      or deteriorated. RESULTS: Normalisation of chest radiographs occurred in 73% of
      the Japanese and 40% of the Finnish patients. The difference between the two
      series was significant (p < 0.001). Gender, young age, presence or absence of
      symptoms or extrapulmonary lesions at diagnosis or treatment with corticosteroids
      did not influence the difference between the two series. Of the 191 Finnish and
      309 Japanese patients with initial stage I disease a normal chest radiograph was
      obtained in 47% of the Finnish and 76% of the Japanese patients (p < 0.001),
      despite the fact that the Finnish series included patients with erythema nodosum,
      who had a 59% normalisation rate. Of the 186 Finnish and 125 Japanese patients
      with initial stage II disease, normalisation of the chest radiographs was seen in
      36% of the Finnish and in 73% of the Japanese patients (p < 0.001). No difference
      in normalisation rate was seen between stage III patients. CONCLUSION: The
      prognosis of pulmonary sarcoidosis in Japanese patients in Hokkaido is
      significantly better than that in Finland defined as normalisation rate of the
      chest radiographs.

PMID- 10957765
TI  - Sarcoidosis: a long-term follow up study.
AB  - BACKGROUND AND AIM OF WORK: The study investigated the occurrence, time and mode
      of presentation, clinical features, course of pulmonary disease and prognosis of
      all patients with sarcoidosis looked after by one physician in a district general
      hospital during the period 1965-1996. The hospital covered a catchment population
      of 150,000. METHODS: A detailed review of 212 patient notes was carried out with
      the aid of a purposely designed structured data collection form. Postal
      questionnaires were sent to those patients not currently attending to determine
      survival/state of health. Death certificates were analysed to determine the cause
      of death. RESULTS: A diagnosis of sarcoidosis was based on clinical grounds in 63
      of the 212 cases, with histological proof confirming sarcoidosis in 149 cases.
      There was a slightly higher incidence in females than males, with four familial
      instances documented. There was pulmonary involvement in 192 cases classified in
      the usual way at presentation and the course of these patients was studied.
      Patients with Stage 1 and 2 disease had resolution rates in excess of 80%, and
      Stage 3 50%. For the remainder, two patterns emerged: one group with persistent
      infiltration or fibrosis but little disability or disease progression, and
      another with advancing disease refractory to steroid therapy with a bad
      prognosis. CONCLUSIONS: The good prognosis of patients with Stage 1 disease was
      confirmed. There were fewer patients presenting with Stage 2 and 3 disease and
      their prognosis was better than in other published studies. Overall, the numbers
      of patients progressing from one stage to another was small. Although there was a
      small group of patients with steroid-refractory, progressive, fibrosis with a bad
      prognosis, the mortality rate from sarcoidosis in this study was small.

PMID- 10957766
TI  - Bronchoalveolar lavage macrophage-lymphocyte clusters in granulomatous disease
      are linked to lymphocytosis.
AB  - BACKGROUND AND AIM OF THE WORK: Clusters of macrophages associated with
      lymphocytes (ML clusters) have been observed among the bronchoalveolar lavage
      (BAL) cells of patients with pulmonary disease. We tested the hypothesis that ML
      clusters might be found among the BAL cells from patients with granulomatous
      disease. METHODS: We measured the number of ML clusters among the BAL cells from
      normal controls (n = 13), sarcoidosis patients (n = 18), beryllium-sensitized
      (BeS) patients (n = 21) and chronic beryllium disease (CBD) patients (n = 15).
      RESULTS: ML clusters were observed in the BAL cells of all groups, but at
      different frequencies: normal 8.5% (median, range 2-15%); BeS 7% (range 2-31%);
      sarcoidosis 14% (range 4-50%); and CBD 17% (range 6-73%). This data suggested
      that ML clusters were increased in granulomatous lung disease. However, the
      percentage of ML clusters strongly correlated with the BAL lymphocyte percentage
      (rho = 0.79). Cohort analysis showed that increases in macrophages having 2, 3 or
      > 3 associated lymphocytes correlated with an increase in lymphocyte percentage.
      CONCLUSIONS: An increase in ML clusters in BAL cells is not specific for
      granulomatous disease and is associated with the increase in BAL lymphocytes.

PMID- 10957767
TI  - Sarcoidosis and dermatomyositis in a patient with hemoglobin SC. A case report
      and literature review.
AB  - Although sarcoidosis has occasionally been associated with hemoglobinopathies,
      its association with dermatomyositis is extremely rare. A 24 y/o African American
      male with hemoglobin SC disease developed proximal weakness. He had heliotrope
      rash, muscle weakness, elevated serum CK, myositis by EMG, and no malignancy. A
      muscle biopsy confirmed dermatomyositis. Two years later, he was hospitalized
      with constitutional and respiratory symptoms and parotid enlargement. Chest X-ray
      and CT scan showed diffuse micronodular infiltration in both lungs and
      mediastinal lymphadenopathy. A transbronchial lung biopsy revealed non-caseating
      granulomata consistent with sarcoidosis. AFB and fungal stains and cultures were
      negative. Thus, in this case, sarcoidosis developed after or in association with
      dermatomyositis. A review of world's literature showed five other non-identical
      cases of dermatomyositis associated with sarcoidosis.

PMID- 10957768
TI  - Neurosarcoidosis presenting as syncope.

PMID- 10957769
TI  - [10 years PSA--chemoprevention].

PMID- 10957770
TI  - [Chemoprevention of prostatic carcinoma].
AB  - Chemoprevention of prostate cancer is the administration of agents to prevent,
      inhibit, or delay progression of prostate cancer. Asian men have a much lower
      incidence of prostate cancer than men in Europe or the USA. Asian food includes
      low-fat, high-fiber diets, which provide a rich supply of weak dietary estrogens.
      These estrogens have been proposed as chemopreventive agents. In addition to
      their estrogenic activity, many of these plant compounds can interfere with
      steroid metabolism and bioavailability and can also inhibit enzymes, such as
      tyrosine kinase or topoisomerase, which are important for cellular proliferation.
      In addition, nutritional factors such as reduced fat intake, vitamin E, vitamin
      D, and selenium may have a protective effect against prostate cancer. The fact
      was proven in large epidemiological studies as well as experimental observations.
      In the animal model, the progression of established tumors can be inhibited by
      these agents. A number of studies to investigate the effect of possible
      chemopreventive agents for men at high risk of prostate cancer are established.
      End points for evaluation are mainly based on changes in PSA, changes of
      histological precursors, or time of onset of clinical disease. The concept of
      chemoprevention in prostate cancer might have a significant impact on the
      incidence and mortality of this disease.

PMID- 10957771
TI  - [From antigen to tumor marker. Results of research regarding PSA and its clinical
      applications].
AB  - The determination of prostate-specific antigen is credited with dramatic advances
      in the early detection of men with prostatic carcinoma. This report summarizes
      the history of biochemical research and current status of prostate-specific
      antigen in tumor diagnostics.

PMID- 10957772
TI  - [Molecular forms of prostate-specific antigen and human kallikrein 2 as possible
      indicators in prostatic carcinoma diagnosis].
AB  - Prostate-specific antigen (PSA) is the most useful marker in the early detection
      of prostate cancer and in the monitoring of patients with this diagnosis.
      Molecular forms of PSA and human kallikrein 2 (hK2) have been used to
      discriminate between benign prostatic hyperplasia and prostate cancer, as well as
      for the detection of prostate cancer within the gray zone of PSA. In this
      respect, a literature survey on the diagnostic validity of free PSA (fPSA)
      related to total PSA (tPSA), PSA bound to alpha 1-antichymotrypsin (ACT-PSA), and
      complexed PSA (cPSA) is given together with our own results. The ratio of
      fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate
      cancer diagnosis based on tPSA measurements. The number of biopsies can be
      reduced in the total PSA range of 4-10 micrograms/l. Furthermore, carcinomas can
      be detected in patients with PSA values less than 4 micrograms/l. ACT-PSA or cPSA
      alone and the calculated derivatives are not superior in their discriminatory
      power compared with tPSA and the fPSA% value. The other molecular PSA forms and
      hK2 are still objects of research and their diagnostic significance needs to be
      evaluated in more extensive clinical trials.

PMID- 10957773
TI  - [Additional aids in detection of prostate carcinomas? PSA-prostatic volume
      quotient, PSA-doubling time, age-dependent PSA reference values and PSA in
      urine].
AB  - Different concepts to improve the clinical utility of prostatic-specific antigen
      (PSA) for prostate cancer detection have been developed. PSA density and
      transition zone PSA density are not useful screening tools due to a high
      variability of prostate volume measurement. PSA velocity monitors the change in
      PSA in a 2-year period, therefore it is not suitable for treatment decisions in
      men with serum PSA levels between 4 and 10 ng/ml. Measurement of urinary PSA is
      not helpful for prostate cancer detection. Age-specific PSA reference ranges
      provide greater sensitivity for cancer detection in younger men at the expense of
      a greater negative biopsy rate. In older men unnecessary biopsies could be
      spared. However, this might lead to a lower sensitivity in these patients,
      missing possibly clinically insignificant tumors.

PMID- 10957775
TI  - [Mass screening for detection of prostatic carcinoma].
AB  - Active screening has been advocated around the world with reference to the
      favorable results of breast cancer screening. The risk of overdiagnosis and
      subsequent overtreatment by aggressive therapies fuels the arguments against
      screening. The value of early detection of prostate cancer in asymptomatic stages
      remains to be determined. There is a lack of pretreatment prognostic factors in
      order to distinguish those cancers which are life threatening from those which
      will have a relatively benign or even asymptomatic course. The benefit of
      prostate cancer screening, in terms of reducing disease-specific mortality and
      improvement of quality of life, can probably only be proven by a randomized
      study. Such studies are ongoing in the USA, Canada, and Europe.

PMID- 10957774
TI  - [Early detection of prostatic carcinoma in urologic practice with digital rectal
      examination and prostate-specific antigen. Early Detection Project Group].
AB  - For the early detection of prostate cancer, a patient should undergo digital
      rectal examination (DRE) and PSA investigation. Follow-up of increased PSA levels
      detects nearly 80% of cancers. Positive predictive value of suspicious DRE and
      PSA is about 50%. Whereas in the first evaluation of this case-finding trial
      about 70% of the patients had organ-confined cancers, nearly all of the detected
      cancers in the follow-up investigation were organ confined. The increased number
      of organ-confined cancers detected in early periodical examinations can lead to a
      reduction of mortality and morbidity from prostate cancer.

PMID- 10957776
TI  - [Improvement of transrectal ultrasound. Artificial neural network analysis (ANNA)
      in detection and staging of prostatic carcinoma].
AB  - As a result of the enhanced clinical application of prostate specific antigen
      (PSA), an increasing number of men are becoming candidates for prostate cancer
      work-up. A high PSA value over 20 ng/ml is a good indicator of the presence of
      prostate cancer, but within the range of 4-10 ng/ml, it is rather unreliable.
      Even more alarming is the fact that prostate cancer has been found in 12-37% of
      patients with a "normal" PSA value of under 4 ng/ml (Hybritech). While PSA is
      capable of indicating a statistical risk of prostate cancer in a defined patient
      population, it is not able to localize cancer within the prostate gland or guide
      a biopsy needle to a suspicious area. This necessitates an additional effective
      diagnostic technique that is able to localize or rule out a malignant growth
      within the prostate. The methods available for the detection of these prostate
      cancers are digital rectal examination (DRE) and Transrectal ultrasound (TRUS).
      DRE is not suitable for early detection, as about 70% of the palpable
      malignancies have already spread beyond the prostate. The classic problem of
      visual interpretation of TRUS images is that hypoechoic areas suspicious for
      cancer may be either normal or cancerous histologically. Moreover, about 25% of
      all cancers have been found to be isoechoic and therefore not distinguishable
      from normal-appearing areas. None of the current biopsy or imaging techniques are
      able to cope with this dilemma. Artificial neural networks (ANN) are complex
      nonlinear computational models, designed much like the neuronal organization of a
      brain. These networks are able to model complicated biologic relationships
      without making assumptions based on conventional statistical distributions.
      Applications in Medicine and Urology have been promising. One example of such an
      application will be discussed in detail: A new method of Artificial Neural
      Network Analysis (ANNA) was employed in an attempt to obtain existing subvisual
      information, other than the gray scale, from conventional TRUS and to improve the
      accuracy of prostate cancer identification.

PMID- 10957777
TI  - [Ileal conduit bleeding in portal hypertension. A rare complication].
AB  - The ileal conduit is a simple and safe supravesical urinary diversion with few
      postoperative complications. In patients with liver disease with portal
      hypertension, however, the risk of recurrent, peracute conduit bleeding is
      increased. While the diagnosis is simple, several therapeutic options are
      available. In most cases the bleeding comes from stomal varices, that can be
      controlled with local sclerotherapy with 3% Ethoxyscerol or ligation of the
      bleeding vessel. The resection of the part of the conduit carrying the varices is
      an option if bleeding is life threatening or the source cannot be localised. If
      bleeding recurs excision of the conduit should be considered. Malignant disease
      must be excluded as a bleeding source.

PMID- 10957778
TI  - [Reninoma: a rare cause of hypertension. Case report, review of the literature
      and possibility for organ preserving operation].
AB  - A 20-year-old man with no past medical history and no clinical symptoms was
      referred for examination because of severe hypertension. The blood chemistry
      studies showed elevated levels of peripheral renin with evidence of secondary
      aldosteronism. Sonography and computed tomography demonstrated a mass of the left
      kidney. After excluding all other possible causes for severe hypertension,
      excision of the tumor was performed. Histological studies confirmed the diagnosis
      of a juxtaglomerular cell tumor. Reninoma represents a rare but surgically
      curable cause of hypertension. The clinical suspicion of this tumor is very
      important because of the young age of the patients. If the diagnosis is confirmed
      a renal sparing surgery should be the treatment of choice.

PMID- 10957779
TI  - [Treatment of metastatic renal cell carcinoma. Value of immunotherapy compared
      with surgery of metastases].
AB  - The prognosis for patients in whom metastatic renal cell carcinoma (RCC) is not
      treated is unfavorable, with a reported 5-year survival of 0-18%. Before the era
      of immunotherapy and in the absence of effective nonsurgical therapy, resection
      of metastases was the accepted way to prolong survival, giving a 5-year survival
      of 7-69%. Retrospective studies have shown that several clinical factors are
      associated with a relatively good prognosis. Some patients will benefit from
      resection of metastases, but most patients with metastatic RCC are not candidates
      for such aggressive surgery. The use of interleukin-2 has demonstrated that
      immunotherapy can produce durable remissions. Without randomized trials, it is
      difficult to know whether survival is longer than that in untreated patients, but
      there is clear evidence that immunotherapy improves survival and yields long
      lasting remissions in selected patients. Many questions remain concerning quality
      of life and the benefit-to-risk ratio of immunotherapy, but it is the most
      effective treatment for metastatic RCC.

PMID- 10957780
TI  - [Surgery of metastases in renal cell carcinoma].
AB  - Renal cell carcinomas (RCC) are endowed with impressive metastatic potential.
      Patients with RCC who present with apparently solitary metastatic lesions
      represent a small cohort. Due to the different long-term results achieved with
      surgical resection of metastatic RCC lesions, a generally accepted judgement
      about this treatment modality is not possible. Several studies suggest that
      aggressive surgical management can provide an effective treatment, especially in
      patients with solitary pulmonary metastases. Most noteworthy is the fact that
      because of the organ distribution of RCC metastases, surgical therapy is
      dominated by general and thoracic surgeons, neurosurgeons, and orthopaedic
      surgeons. Therefore, an interdisciplinary approach is one of the most important
      key points for a successful outcome in these patients.

PMID- 10957781
TI  - [Diagnosis and therapy of prostatitis syndrome].

PMID- 10957783
TI  - [Lipomatous hypertrophy of the interatrial septum].
AB  - The echocardiographic examination of a female, overweight patient, 71 years of
      age, with left-sided breast cancer, performed in another hospital, revealed a
      tumor of the interatrial septum of 3.2 x 4.0 cm. The patient was transferred to
      our clinic and the finding was identified as a lipomatous hypertrophy of the
      interatrial septum by echocardiography, computer tomography and nuclear magnetic
      resonance imaging. It was confirmed by biopsy and histological examination. The
      lipomatous hypertrophy of the interatrial septum is a rare, benign disease, which
      usually does not cause a hemodynamic significant obstruction of the blood flow.
      An increased incidence of atrial arrhythmias is known to occur in this condition
      and seems to be the only functional restriction.

PMID- 10957782
TI  - The molecular mechanisms of inherited thrombophilia.
AB  - Venous Thromboembolism develops as the result of multiple interactions between
      non-genetic and genetic risk factors. The most important non-genetic risk factors
      are age, tissue damage, oral contraception, pregnancy, obesity and lack of
      physical activity. Inborn factors predisposing to thrombosis are present in the
      majority of patients. These comprise defects affecting the anticoagulant pathways
      of blood coagulation like antithrombin III, protein C and protein S. Together
      these defects are found in 15-20% of thrombophilia families. The relatively rare
      defects of antithrombin III, protein C and protein S stand in contrast to two
      common genetic polymorphisms of procoagulant molecules, factor V-Leiden, the most
      frequent cause for resistance to activated protein C, and the prothrombin 20210 A
      allele. Together, these anomalies are found in almost two third of the
      thrombophilia families. The identification of factor FV-Leiden and prothrombin
      20210 A has allowed to examine in detail interactions between genetic and non
      genetic risk factors of thromboembolism. The results of these studies indicate
      that many symptomatic individuals are endowed with more than one (genetic and/or
      environmental) risk factor. Thrombophilia thus represents an oligogenetic rather
      than monogenetic clinical phenotype, the expression of which is amplified by
      circumstantial risk factors. As a consequence of the "multiple hit" concept, the
      laboratory screening of thrombosis patients needs to include all of the known
      genetic risk factors even if the "clinical" situation seemingly provides
      sufficient "explanation" for a thrombotic event.

PMID- 10957784
TI  - [Hidden intracardiac conduction disturbances and their spontaneous course in
      patients with progressive muscular dystrophy].
AB  - In patients with progressive muscular dystrophy (PMD) invasive electrophysiologic
      studies can detect hidden intracardiac conduction disturbances. The aim of this
      study was a long-term follow-up of these patients. Twelve consecutive patients (9
      m, 3 f, age 28 +/- 4 yrs) without cardiac symptoms and with normal
      echocardiographic findings were included in the study. They suffered from
      different stages of PMD type Erb (n = 4), Becker-Kiener (n = 4), Duchenne (n = 2)
      and Landouzy-Dejerine (n = 2). At the beginning of the study all patients
      underwent an invasive electrophysiologic study (EPS). The follow-up of 5.5 yrs
      included regular clinical visits, ECGs, and Holter recordings (every 3 months) as
      well as an echocardiography every 6 months. In 4 patients the EPS revealed a
      hidden interatrial conduction disturbance (AHRS-ACS 120 +/- 18 ms), and in 10 pts
      an infrahisian conduction disturbance was found (HV max. 156 +/- 4 ms).
      Conduction defects were seen independently from the type of PMD and the stage of
      the disease. During the follow-up the initially hidden interatrial conduction
      disturbance became evident in the surface ECG in 2 of 4 pts. One of them
      developed paroxysmal atrial fibrillation. Five of 10 pts with an initially hidden
      infrahisian conduction disturbance developed an AV block grade I-III and in one
      case additionally a bundle branch block. Four of these pts--whose PMD showed
      progression or who developed congestive cardiomyopathy--needed pacemaker
      implantation because of a first-degree AV block + bifascicular bundle branch
      block (n = 1), a Mobitz II second-degree AV block (n = 1) or a third-degree AV
      block (n = 2). None of the pts with normal findings at the EPS showed abnormal p
      waves, an AV block, or an intraventricular conduction disturbance during the
      follow-up. We conclude that intracardiac conduction disturbances, especially
      infrahisian defects including high-degree AV blocks, are a common finding in pts
      with PMD. Therefore a regular cardiological screening including an ECG and a
      Holter recording is reasonable in these patients.

PMID- 10957785
TI  - [Late diagnosis of Curschmann-Steinert myotonic dystrophy in a female patient
      with dilated cardiomyopathy and in her son].
AB  - A 41 year old woman presented with dyspnoea at rest and swollen legs in the
      emergency room of our centre. She reported a history of slowly progressing
      dyspnoea and oedema in the legs. Physical examination showed signs of
      biventricular congestive heart failure and dysmorphia of the face. Routine
      laboratory examination revealed elevated CK levels without significant elevations
      of the CK-MB isoform. ECG showed complete left bundle branch block and first
      degree atrioventricular block. Echocardiography and angiography showed markedly
      reduced left ventricular systolic function, the ejection fraction was 25%.
      Coronary angiography excluded CAD and there was no evidence for congenital or
      valvular heart disease. The patient also reported a history of a serious
      complication during emergency general anaesthesia and cataracts of both eyes.
      Because of the clinical and chemical findings, the history of cataracts and
      complications during general anaesthesia, a systemic congenital disease of the
      muscular tissue was suspected. Molecular studies revealed a trinucleotide
      amplification at the myotonic dystrophy locus 19q 13.3, so the diagnosis myotonic
      dystrophy Curschmann-Steinert was established. The sixteen year old son of the
      patient suffered from an at this time unknown disease with retardation, muscular
      weakness and myotonia of the face. The diagnosis myotonic dystrophy was evident
      because of the clinical signs and the family history.

PMID- 10957787
TI  - Apical hypertrophic cardiomyopathy due to a de novo mutation Arg719Trp of the
      beta-myosin heavy chain gene and cardiac arrest in childhood. A case report and
      family study.
AB  - Hypertrophic cardiomyopathy (HCM) is a myocardial disease with variable phenotpye
      and genotype. To demonstrate that the mutation Arg719Trp in the cardiac beta
      myosin heavy chain (beta MHC) gene is a high risk factor for sudden death and can
      be associated with an unusual apical non-obstructive HCM, we report the case of a
      6 1/2 year old boy, who suffered cardiac arrest. The proband had a de novo
      mutation of the beta MHC gene (Arg719Trp) on the paternal beta MHC allele and a
      second maternally transmitted mutation (Met349Thr), as was shown previously
      (Jeschke et al. 1998 (11)). Here we report the clinical phenotype of the proband
      and of his relatives in detail. The proband had a marked apical and
      midventricular hypertrophy of the left and right ventricle without obstruction.
      There was an abnormal relaxation of both ventricles. Holter monitoring detected
      no arrhythmia. Ventricular fibrillation was inducible only by aggressive
      programmed stimulation. The boy died 3 1/2 years later after another cardiac
      arrest due to arrhythmia. Five carriers of the Met349Thr mutation in the family
      were asymptomatic and had no echocardiographic changes in the heart, suggesting a
      neutral inherited polymorphism or a recessive mutation. It is concluded that
      there is an association of the mutation Arg719Trp in the beta-myosin heavy chain
      with sudden cardiac death in a young child. Disease history in conjunction with
      the genetic analysis suggests that the implantation of a defibrillator converter
      would have been a beneficial and probably life saving measure.

PMID- 10957786
TI  - [Contraception in patients with congenital heart defects].
AB  - The number of women with congenital cardiac disease, who mature into adulthood is
      increasing. Unfortunately, there are no prospective data published about the
      relative risk of different forms of contraception for these patients. Most women
      with congenital cardiac disease can safely use oral contraceptives, especially
      low-estrogen combination or progestin-only preparations, with the exception of
      those, who are at particular risk because of thromboembolic complications
      (especially in cyanosis, pulmonary hypertension, Eisenmenger reaction, rhythm
      disturbances), fluid retention (especially in reduced ventricular function and
      congestive heart failure), arterial hypertension (important in coarctation),
      infectious complications (endocarditis) or hyperlipidemia. Oral contraceptives
      should be avoided in patients at increased risk for thromboembolic events.
      Intrauterine devices are very effective, have no metabolic side effects and
      merely carry a small risk of endocarditis. Newer devices containing progesterone
      only may put the patients at a still smaller risk. Contraceptive subdermal
      implants (e.g. levonorgestrel) are used with good results in the United States
      for patients with contraindications to estrogen-containing oral contraceptives
      and may well become more widely accepted in patients in Germany in the coming
      years. Barrier methods can be used, but have a higher failure rate, which may be
      unacceptable in patients at risk (e.g. Eisenmenger's). Especially in
      Eisenmenger's, permanent sterilisation should be advised.

PMID- 10957789
TI  - Familial hypertrophic cardiomyopathy associated with prolongation of the QT
      interval.
AB  - In a 61 year old female patient who suffered from atypical chest pain we
      diagnosed long QT syndrome by QTc duration of 467 ms, macroscopic T wave
      alternans and notched T waves in three leads and hypertrophic cardiomyopathy with
      asymmetric thickening of basal parts of the septum (2.0 cm) without relevant
      outflow tract obstruction by echocardiography. Coronary angiography could exclude
      coronary artery disease. In a systematic family screening two sons of the patient
      could also be diagnosed as having long QT syndrome with QTc durations of 472 and
      496 ms and asymmetric septal thickening (1.8 and 2.1 cm, respectively). One of
      these two sons suffered from pre-syncope, the other was asymptomatic despite
      maximum sports activity. In the third son, LQTS and hypertrophic cardiomyopathy
      could be excluded.

PMID- 10957788
TI  - [Single coronary artery with a long left main trunk].
AB  - Coronary anomalies are rare and usually benign. The case of a symptomatic woman
      aged 53 years is presented. Here the single coronary artery with a long left main
      trunk was treated by bypass grafting.

PMID- 10957790
TI  - [Cardiorespiratory desynchronization after acute myocardial infarct].
AB  - The prognosis of cardiac diseases can be estimated from the variability of
      regulation parameters of the cardiovascular system. Changes in the variability of
      a regulation parameter causes disturbances in the synchronisation of interacting
      control loops. Conclusions about the severity of the underlying functional
      impairment can be drawn from these disturbances. This study investigates the
      synchronisation of the control loops of the heart rate and respiration
      (cardiorespiratory synchronisation, CRS) after acute myocardial infarction. We
      investigated 43 patients after myocardial infarction and 27 healthy controls. To
      quantify the CRS the synchronisation in phase of respiration and heart rate was
      assessed. The heart rate variability (HRV) was also assessed. Patients after
      myocardial infarction have a significantly reduced HRV and CRS. There is a non
      linear relationship between HRV and CRS. Patients with left ventricular
      enlargement and reduced left ventricular ejection fraction (< or = 45%)
      significantly differed from the other infarct patients and controls in CRS but
      not in HRV. They had a marked degree of cardiorespiratory desynchronisation and
      were identified by a threshold value. CRS is a measure of the interaction of
      respiration control and heart rate control. After myocardial infarction, a
      reduction of the HRV can be observed. The desynchronisation of the control loops
      of respiration and heart rate especially appears in large infarcts. This can be
      quantitatively assessed by the method presented.

PMID- 10957791
TI  - [Genetic screening of cardiomyopathies].
AB  - Cardiomyopathies comprise a heterogeneous group of primary heart muscle disorders
      with a strong genetic component. Nearly all cases of hypertrophic cardiomyopathy
      and at least 20-30% of cases with dilated cardiomyopathy are due to autosomal
      dominant mutations. The extent of genetic factors for arrhythmogenic right
      ventricular and restrictive cardiomyopathy is less clear. Recent studies have
      demonstrated that genetic causes of all cardiomyopathies are highly heterogeneous
      with more than 25 disease gene loci. Although the ability to diagnose
      cardiomyopathies at the molecular level has advanced, our understanding of
      disease pathways and the knowledge of individual diseases causing mutations has
      had little impact on the clinical management of patients. Once current technical
      limitations for large-scale mutation analysis are overcome, broad
      genotype/phenotype correlation studies may answer important clinical issues such
      as the precise relation between distinct mutations and the risk of sudden death,
      course of the disease and treatment of patients.

PMID- 10957792
TI  - [Dementia praecox and dysnoia in clinical observation notes by S.S. Korsakov].

PMID- 10957793
TI  - [Auditory and verbal agnosia in the left-handed patient: comparison of
      neuropsychological data, magnetic resonance and positron emission tomography].
AB  - A case of the post-traumatic auditory-and-speech agnosia in a left-handed female
      patient is presented. The patient (a professional painter) showed satisfactory
      recovery in painting, speech production, reading and writing, whereas a severe
      deficit in auditory recognition of speech, melodies and rhythms persisted over
      time. She was also impaired in some aspects of visual recognition including
      prosopagnosia. To study this patient comprehensively, a neuropsychological
      assessment was combined with structural (magnetic resonance imaging-MRI) and
      metabolic (positron emission tomography--PET) data. Both PET and MRI revealed a
      large bilateral cortical damage in the medial basal cortex of the frontal,
      temporal and occipital lobes along with the anterior half of the lateral temporal
      cortex. In the left hemisphere the damaged area involved the whole temporal lobe,
      a large part of the occipital lobe and the opercular frontal and parietal
      regions. The relationship of the symptoms with the brain damage extension is
      discussed taking into account the left-handedness of the patient.

PMID- 10957794
TI  - [Acute cerebrovascular disorders during surgical operations on abdominal organs].
AB  - Acute cerebrovascular disorders were found in 4.78% of the patients operated on
      for acute abdominal diseases. Such disorders were revealed during the first 3
      days of the postoperative period in 86.9% and appeared as transitory ischemic
      attacks (21.9%), acute hypertensive encephalopathy (12.4%), ischemic stroke with
      reversible neurological deficit (27.6%), ischemic stroke with stable neurological
      deficit (20%), hemorrhagic stroke (2.9%), mixed stroke (2.9%). The pathogenesis
      of vascular disorder in examined cases included systemic and cerebral hemodynamic
      disorders, acid-alkaline imbalance, impaired blood gas composition and
      biochemical and physicochemical blood properties, altered cranial great arteries,
      cerebrovascular emboli, endogenous intoxication and age-related changes. In the
      first 24 postoperative hours, actovegin and instenon therapy accelerated
      neurological deficit regression and recovered cerebral hemodynamics in
      postoperative strokes.

PMID- 10957795
TI  - [Specific aspects of endogenous mental disorders with seasonal depressions].
AB  - The clinical features and the course of seasonal depressions in endogenous mental
      diseases were studied with psychopathological and follow-up methods. The seasonal
      depressions in 50 patients were developed in the psychopathological structure of
      manic-depressive psychosis (22 patients), schizoaffective psychosis (23) and
      schizoaffective variant of schizophrenia (5). There were found the considerable
      differences in the characteristics of seasonal depressions in the indicated
      endogenous psychoses. The was established that spring summer depressions had more
      favorable prognostic meaning in comparison with fall-winter depressions. There
      was shown that changes or disappearance of the seasonal rhythm of depression's
      development was prognostic unfavourable sign and pointed to the change to the
      worse of disease.

PMID- 10957796
TI  - ["Addictive" personality].
AB  - The paper presents an observation of 100 patients (84 men, 16 women) aged 13-50
      years (mean 25 +/- 6.7 years) with different forms of drug addiction, namely:
      heroin, opiate, pervitin-ephedrone addiction as well as polynarcomanias. The
      duration of drug addiction ranged from 1 to 24 years (mean 4.35 +/- 2.25 years).
      No matter what the type of a drug was abused, all patients had levelled off
      individual personal traits and some formed peculiar narcomanic defect. It was
      characterized by elevated excitability, gradually progressing affective disorders
      in form of dysphoric or apathoabulic depressions, affective lability, prevailing
      hysteric-excitable forms of responses, psychosocial dysfunction as gradually
      decreasing interests, different anomalies of the emotional sphere, impuls control
      disorders, including sexual ones. A moral-ethic decrease was pronounced as well
      as transient intellectual-mnestic disturbances. By and large personality
      disorders were qualified as an "addictive personality".

PMID- 10957797
TI  - [The influence of transcranial micropolarization on convulsive manifestations in
      children].
AB  - Eighteen patients with infantile cerebral paralysis and organic brain damage
      underwent to therapeutical sessions of transcranial micropolarization directed to
      decrease the incidence of convulsive fits. Transcranial micropolarization of the
      posterior temporal and parietal areas caused a marked decrease in the incidence
      of convulsive fits and made the electroencephalographic pattern normal. This
      effect was caused by the target exposure of the structures responsible for the
      formation and regulation of brain convulsive activity to constant current through
      the respective morphofunctional linkages of the cortical areas.

PMID- 10957798
TI  - [Physiopathological and chemopathological mechanisms of central motor disorders
      in amyotrophic lateral sclerosis].
AB  - A complex study of pathophysiological characteristics of corticospinal systems
      was performed in patients with amyotrophic sclerosis (ALS) by transcranial
      magnetic resonance stimulation (TMRS) and estimation of the levels of mediatory
      amino acids in the cerebrospinal fluid (CSF). There was a time course of changes
      in the excitability of cortical motor neurons (MNs) and in the functional status
      of the pyramidal tract as ALS progressed. The large cortical MNs were found to be
      afflicted just at early stages by further involving their axonal systems into the
      pathological process. As a result, mainly fine slowly conducting axons of MNs
      functioned at the later stages of the disease. Neurochemical changes correlated
      with the duration of the disease and were supposed to play an important role in
      the pathogenesis of ALS. Besides, a significant correlation revealed by TMRS
      between the pathology of the corticospinal tract and the cerebrospinal fluid
      levels of glutamate confirmed the role of glutamate as a the main
      neurotransmitter of this motor system. The results of the study also confirm the
      significance of excitotoxic mechanisms in central motor disorders in ALS.

PMID- 10957799
TI  - [The study of polymorphism of dopamine D2 receptor gene in men from different
      ethnic groups with acute alcoholic psychosis].
AB  - The polymerase chain reaction of DNA synthesis was used to analyze the
      polymorphism of TaqI A and NcoI loci of dopamine D2 receptor gene (DRD2) in 170
      Tatar and Russian males with acute alcoholic psychosis. No differences were found
      in the distribution of frequencies of genotypes and alleles of DRD2 gene between
      the populations. There were differences in the distribution of the frequencies of
      genotypes of the locus TaqI A and haplotypes of the gene DRD2 were revealed
      between patients and controls of the same nationality; moreover these differences
      were significant in the Russians. The findings suggest that alcoholics show a
      selection aimed at eliminating individuals with haplotypes who carry Al and N2
      alleles and who are homozygous by one of these alleles. This may account for a
      decrease in the frequency of locus TaqI A genotypes carrying A1 allele, primarily
      A1/A1 homozygotes and for the loss of haplotypes of TaqI A and NcoI loci of the
      gene DRD2 -A1N1N2, A1A2N2 in men with acute alcoholic psychosis as compared with
      the controls.

PMID- 10957800
TI  - [Morphopathology of cerebral arteries in combined cerebral and coronary
      atherosclerosis].
AB  - Taking into consideration the age-specific and adaptive changes of the vascular
      wall, pathomorphologic features of cerebral atherosclerosis were revealed in 236
      individuals who died of ischemic heart disease and in 17 patients undergone extra
      intracarotid microshunting on the basis of the data obtained from
      pathomorphologic analysis of the great arteries of the brain. There was a
      statistically significant prevalence of both the size of the area of
      atherosclerotic lesions and the incidence of stenosis of the great arteries of
      the brain in individuals with combined atherosclerosis of cerebral and coronary
      atherosclerosis. Type-specific peculiarities of atherosclerosis in the areas of
      reduced blood flow in stenosis of extra- and intracranial arteries were
      determined.

PMID- 10957801
TI  - [Memory and its disorders].

PMID- 10957802
TI  - [Therapy of mental disorders in Chernobyl accident victims with dyscirculatory
      encephalopathy of mixed genesis (practical considerations)].

PMID- 10957803
TI  - [Glutamine synthetase and related protein in the frontal cortex in
      schizophrenia].

PMID- 10957804
TI  - [A case of craniovertebral anomaly as a combination of ischemic heart disease and
      stenosis of the great foramen].

PMID- 10957805
TI  - [The role of serotonin and serotonin receptors in the pathogenesis of migraine
      and in the mechanisms of action of anti-migraine drugs].

PMID- 10957807
TI  - [Vertebral osteochondrosis: an anti-gravitation adaptation disease of an adult
      (postchordal)].

PMID- 10957806
TI  - [Hostility and a human health problem].

PMID- 10957808
TI  - [Gonadotropin stimulation of progesterone production of granulosa cells derived
      from in vitro fertilization procedures: comparison of the in vitro biopotency of
      recombinant follicle stimulating hormone, recombinant luteinizing hormone nad
      recombinant human chorionic gonadotropin].
AB  - The aim of this study was to investigate the effects of recombinant human
      gonadotrophins (follicle stimulating hormone [rFSH], luteinizing hormone [rLH]
      and human chorionic gonadotrophin [rhCG]) on granulosa-lutein cell progesterone
      production in long-term culture. Cultures were maintained for 9 days including a
      preincubation period for 3 days. Cells obtained from gonadotrophin-stimulated
      cycles produced increasing amounts of progesterone during the preincubation
      period reaching a maximum concentration on day 3. Granulosa cells in absence of
      serum secreted significantly lower levels of progesterone than in its presence
      and showed moderate responses to rhCG. Addition of serum (foetal calf serum, FCS)
      to the culture medium enhanced progesterone output in both control and rhCG
      stimulated cultures in a dose-dependent manner. However, in absence of rhCG,
      granulosa cell progesterone production declined towards the end of culture even
      in the presence of constantly high FCS levels. All three recombinant
      gonadotrophins stimulated progesterone accumulation. Recombinant FSH and rLH,
      applied in the dose interval of 0.001-0.01-0.1 IU/ml, caused clear dose-related
      increases in progesterone production. Progesterone accumulation was also
      significantly augmented by the presence of rhCG (range of doses 0.01-0.1-1-10
      IU/ml), but this effect was dose-dependent only between 0.1-10 IU/ml dose
      intervals with the maximum stimulation occurred at the dose of 0.1 IU/ml rhCG.
      From our results it can be concluded that granulosa cells require both serum
      supplementation and gonadotrophin stimulation for optimal progesterone synthesis.
      Recombinant FSH, completely devoid of LH activity, was equivalent to rLH and rhCG
      in terms of stimulation of progesterone production of luteinized human granulosa
      cells.

PMID- 10957809
TI  - [Interaction of immunosuppressive drugs in mice with special regard to bacterial
      translocation].
AB  - Following intraperitoneally (i.p.) applied treatment with 12.5 mg/mouse
      prednisolonum (PR) no bacterial translocation (BT) was observed in mice. The PR
      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, RP can be suitable for combined application with other
      immunosuppressive agents as it can increase immunosuppression without increase of
      side-effect such as those induced by bacterial translocation.

PMID- 10957810
TI  - [Investigation of ambiphilic creams. II. Structural stability].
AB  - Ambiphile creams containing white petrolatum, cetylstearyl-alcohol, Emulgator BTO
      and distilled water were investigated. The elements of the study of structure
      stability were as follows: evaporation of water-phase, mechanical stability of
      structure and its heatstability. A multiplicative function was found between the
      loss of mass of creams and the evaporation time. The viscosity vs. temperature
      function is a two-steps process, it can be divided to a section before melting
      and an other section after it. Decreasing viscosity under shearing time can be
      characterized by a logarithmic equation.

PMID- 10957811
TI  - [Quantitative determination of phenols by bromination surveyed from an unusual
      perspective].
AB  - The substitution reaction of phenols and bromine yields, beside brominated
      phenols, hydrogen bromide as well. In the course of the quantitative
      potentiometric analysis of the latter we may obtain quantitative and structural
      information with regard to the investigated phenol compound in one step. Such
      information may include data regarding substitution of the aromatic ring, the
      detectability of a resorcine-skeleton or phenol-carboxylic acid moiety, etc. With
      the help of the titration curve, sometimes one can detect two subsequent reaction
      steps or two simultaneously existing materials on the basis of the measured
      hydrogen bromide/brominated phenol ratio. We demonstrate here how and old
      technique can be used to solve analytical problems with new perspective, as
      exemplified by the cases of phenol, resorcine, 8-oxy-quinoline and salicylic
      acid.

PMID- 10957812
TI  - Potential civil liability of corporate health and safety professionals under
      workers' compensation systems.

PMID- 10957813
TI  - Chemical and biological terrorism preparedness--Web-based resources.

PMID- 10957814
TI  - Control of ergonomic hazards in commercial drycleaning. National Institute for
      Occupational Safety and Health.

PMID- 10957815
TI  - Electrostatic N-95 respirator filter media efficiency degradation resulting from
      intermittent sodium chloride aerosol exposure.
AB  - The effects of intermittently loading small masses of sodium chloride aerosol on
      the filtration efficiency of N-95 filtering facepiece respirators was
      investigated. The National Institute for Occupational Safety and Health (NIOSH)
      certifies that N-95 respirators must provide at least 95 percent filtration
      efficiency against a sodium chloride aerosol challenge as per the respirator
      certification (42 CFR 84) test criteria. N-95 respirators are specified for
      protection against solid and water-based particulates (i.e., non-oil aerosols).
      New N-95 respirators from three different manufacturers were loaded with 5 +/- 1
      mg of sodium chloride aerosol one day a week, over a period of weeks. Aerosol
      loading and penetration measurements were performed using the TSI 8130 Filter
      Tester. Respirators were stored uncovered on an office desktop outside the
      laboratory. To investigate environmental and temporal effects of filters being
      stored without sodium chloride exposure, control respirators were stored on the
      desk for various lengths of time before being initiated into weekly testing. For
      all manufacturers' respirators, the controls showed similar initial penetrations
      on their day of initiation (day zero) to those of the study samples on day zero.
      As the controls were tested weekly, they showed similar degradation rates to
      those of the study samples. Results show that some of the manufacturers' models
      had penetrations of greater than 5 percent when intermittently exposed to sodium
      chloride aerosol. It is concluded that intermittent, low-level sodium chloride
      aerosol loading of N-95 respirators has a degrading effect on filter efficiency.
      This reduction in filter efficiency was not accompanied by a significant increase
      in breathing resistance that would signal the user that the filter needs to be
      replaced. Furthermore, it was noted that the effect of room storage time prior to
      initial exposure was much less significant.

PMID- 10957816
TI  - Electrostatic respirator filter media: filter efficiency and most penetrating
      particle size effects.
AB  - New electrostatic filter media has been developed for use in 42 CFR 84 negative
      pressure particulate respirator filters. This respirator filter media was not
      available for evaluation prior to the change from 30 CFR 11 to 42 CFR 84. Thus,
      characterization of this filter media is warranted. In this study, the new 42 CFR
      84 electrostatic respirator filters were investigated with respect to filter
      penetration and most penetrating particle size. Three different models of N95
      filters, along with one model each of the N99, R95, and P100 class filters were
      used in this study. First, three of each filter were loaded with a sodium
      chloride (NaCl) aerosol, and three of each filter were loaded with a dioctyl
      phthalate (DOP) aerosol to obtain normal background penetration results for each
      filter. Then, two new filters of each type were dipped in isopropanol for 15
      seconds and allowed to dry. This isopropanol dip should reduce or eliminate any
      electrostatic charge on the fibers of each filter, as reported in the technical
      literature. These dipped filters, along with controls of each filter type, were
      tested on a TSI 8160 filter tester to determine the most penetrating particle
      size. These same filters were then tested against a NaCl aerosol to get final
      penetration values. Electret filters rely heavily on their electrostatic charge
      to provide adequate filter efficiencies, and correlations between penetration and
      a filter's electrostatic characteristics are found in the technical literature.
      In all six of the filter models tested, filter penetration values increased
      considerably and the most penetrating particle size noticeably shifted toward
      larger particles. These results are important in better understanding how these
      new filter materials perform under various conditions, and they indicate the need
      for additional research to define environmental conditions that may affect
      electrostatic filter efficiency.

PMID- 10957817
TI  - Size distribution of mist generated during metal machining.
AB  - Mist generated by machining processes is formed by three mechanisms: impaction,
      centrifugal force, and evaporation/condensation. This study characterized the
      size distribution of soluble and mineral oil mists that resulted from these
      formation mechanisms. Salient parameters influencing the particle size
      distributions also were identified. Variables investigated included metalworking
      fluid and machining characteristics. The size distribution of the mist generated
      on a small lathe by each mechanism was measured using an Aerosizer LD. For
      impaction, only the mineral oil viscosity influenced the mass median diameter of
      the mist. No parameter affected the geometric standard deviation. High-viscosity
      mineral oil mist had a mass median diameter of 6.1 microns and a geometric
      standard deviation of 2.0. Low-viscosity mineral oil mist had a mass median
      diameter of 21.9 microns and a geometric standard deviation of 2.2. The mass
      median diameter of the mist generated by centrifugal force depended on the type
      of metalworking fluid, fluid flow, and rotational speed of the lathe. Mass median
      diameters for low-viscosity mineral oil mist ranged from 5 to 110 microns. Mass
      median diameters for soluble oil mist varied between 40 and 80 microns. The
      average geometric standard deviation was 2.4, and was not affected by any
      parameter. The mass median diameter and geometric standard deviation of the mist
      generated by evaporation/condensation varied with the type of metalworking fluid.
      The mineral oil mist and soluble oil mist mass median diameters were 2.1 microns
      and 3.2 microns, respectively. No machining or fluid parameter was important
      because the mist size distribution depended on the rate of condensation,
      coagulation processes, and the dynamics of the apparatus. Using the size
      distribution data from all three mechanisms, the estimated inhalable, thoracic,
      and respirable fractions of the total mass generated for each metalworking fluid
      were 60 percent, 12 percent, and 8 percent, respectively. To minimize exposure to
      the inhalable mass fraction, the amount of mist generated by centrifugal force
      must be reduced or the size of the drops generated must be increased. Altering
      the machining or fluid parameters did not change the mist size distribution and
      reduce exposure to the respirable mass fraction.

PMID- 10957818
TI  - Emission of ozone and organic volatiles from a selection of laser printers and
      photocopiers.
AB  - To estimate the impact of office equipment on the quality of indoor air, the
      emission of ozone and organic volatiles was measured from one photocopier and
      four laser printers, three of which operated according to traditional corona
      discharge technology. The laser printers equipped with traditional technology
      emitted significant amounts of ozone and formaldehyde. Lesser amounts of other
      volatile aldehydes were emitted during printing. The photocopier emitted mainly
      ozone. In a well-ventilated office environment, the amounts encountered here for
      individual volatiles were within recommended maximum exposure limits for a
      reasonable density of printers. Because it is not known whether the concentration
      of irritating volatiles, such as formaldehyde, should be kept lower in an ozone
      rich environment or not, and because emissions in the immediate vicinity of the
      printers exceeded recommendations, the authors recommend that laser printers
      equipped with the traditional corona rods not be placed beside or immediately at
      the working site of office personnel. This way, ozone concentrations can be kept
      below recommended maximum exposure limits, provided that the ventilation rate is
      adequate. Further, it seems that if a reliable quantitative comparison of total
      organic volatiles prior to and during printing is to be made, the inertness of
      the sorbent toward ozone should be confirmed.

PMID- 10957819
TI  - Resolution of sick building syndrome in a high-security facility.
AB  - The main objective of this article is to serve as a case study for other
      industrial hygiene (IH) professionals' review as a "real world" effort in
      responding to a facility perceived as "sick" by its occupants. As many industrial
      hygienists do not have extensive backgrounds in evaluating microbial air
      contaminants or the mechanical function of building HVAC units, the overall
      intent is to provide "lessons learned" to IH generalists who may be asked to
      participate in indoor environmental quality (IEQ) surveys. In September 1994, a
      suspected case of "sick building syndrome" was investigated (with significant
      airborne fungal loads confirmed) at a communications center after numerous
      occupants reported upper respiratory disease and/or allergy-type symptoms. The
      setting was a two-story structure approximately 30 years old, with a normal
      occupancy load of 350 to 400 persons. In addition to continual structural
      modifications, the central HVAC air conditioning systems had poor maintenance
      histories. Inspection of HVAC components revealed visible fungal growth on air
      filters and air ducts and in cooling fan condensate drip pans. Fungal air samples
      were collected with an Anderson N6 air sampler and Sabouraund dextrose agar
      media. Over a study period of 23 months, three rounds of 26 air samples were
      collected for 5 minutes each at 28.3 liters/minute airflow. Cultures exhibited
      fungi such as Aspergillus, Penicillium, Alternaria, and Cladosporium. Certain
      strains of these fungi produce mycotoxins that may cause a variety of deleterious
      health effects such as those described by occupants. Initial 1994 airborne fungal
      concentrations ranged from 85 to 6157 colony forming units (CFUs) per cubic meter
      of sampled air (CFU/m3). Some investigators have reported fungal concentrations
      as low as 245 CFU/m3 associated with complaint sites in other buildings.
      Remediation efforts involved hiring a dedicated mechanic to implement a HVAC
      preventive maintenance program (including regular replacement of all HVAC air
      filters and cleaning of accessible components with water/bleach solution). Post
      abatement January 1996 re-sampling revealed a significant drop in airborne fungal
      colonies up to 97 percent (range = 21 to 1092 CFUs/m3)--which also coincided with
      physicians at the local hospital sensing a qualitative reduction in patient
      visits from facility workers. To address seasonal bias, a final August 1996 air
      sample round revealed a range of 14 to 500 CFUs/m3. Of the 21 workspaces sampled
      in all three rounds, nine continued to show a decline in CFUs/m3 from September
      1994 baseline counts. These results demonstrate the critical role of an ongoing
      HVAC maintenance program for reducing potential reservoirs of fungal organisms in
      indoor work environments. Building renovations (especially those involving major
      changes to building layout and usage) can adversely affect IEQ if plans do not
      include coordinated updates and regular preventive maintenance of HVAC systems.
      Eventual negative outcomes can be reduced occupant productivity and deleterious
      health effects.

PMID- 10957820
TI  - Exposure assessment for a large epidemiological study of aircraft manufacturing
      workers.
AB  - Methods were developed to assess exposure to a wide variety of chemicals for
      nearly 80,000 workers involved in manufacturing aircraft since 1928. The
      facilities, now closed, consisted of four major plants, over 200 buildings, and a
      changing workforce during 60 years of operation. To access chemical exposures by
      specific jobs and calendar years, we reviewed complete work histories, examined
      detailed job descriptions available going back to 1940, interviewed long-term
      employees, conducted walk-through visits of aircraft manufacturing plants,
      reviewed comprehensive environmental assessment reports and industrial hygiene
      surveys on the facilities, and built on experience gained in previous studies of
      the aircraft industry. Using computer-based imaging systems, we examined and
      evaluated the complete work histories found on service record cards for the
      cohort and abstracted detailed information on all jobs held among the factory
      workers who had been employed for at least one year. Jobs were classified into
      one of three exposure categories related to the use of specific chemicals:
      routine, intermittent, and none, and these classifications were subsequently used
      in the epidemiological analyses. The approach to exposure assessment began with
      the most general categorization of employees (i.e., all workers) and then became
      progressively more specific, that is, factor workers, job families (similar
      activities), job titles, and jobs with chemical usage (exposure potential).
      Because exposure surveys were limited or absent during the early years of plant
      operations, we did not assign quantitative measures of exposure to individual job
      activities. Instead, we used as our exposure metric, the length of time spent in
      jobs with potential exposure to the chemical. Important occupational exposures
      included chromate-containing compounds such as used in paint primers,
      trichloroethylene and perchloroethylene used as vapor-state degreasing solvents,
      and a broad range of other solvents.

PMID- 10957821
TI  - The role of pain anxiety, coping, and pain self-efficacy in rheumatoid arthritis
      patient functioning.
AB  - Anxiety about pain is increasingly recognized as one factor contributing to
      increased pain perception and pain behavior [McCracken, L. M., Faber S. D., &
      Janeck A. S. (1998) Pain-related anxiety predicts nonspecific physical complaints
      in persons with chronic pain. Behavior Research and Therapy, 36, 621-630;
      McCracken L., & Gross R. (1995). The pain anxiety symptoms scale (PASS) and the
      assessment of emotional responses to pain. Innovations in clinical practice: a
      source book, 14, 309-321]. To assess this emotional reaction to pain in chronic
      pain patients, McCracken, Zayfert and Gross [McCracken, L., Zayfert, C., & Gross,
      R. (1992). The Pain Anxiety Symptom Scale: development and validation of a scale
      to measure fear of pain. Pain, 50, 67-73] developed the Pain Anxiety Symptom
      Scale (PASS) composed of four subscales: Cognitive Anxiety, Fearful Appraisal,
      Escape Avoidance and Physiological Anxiety. The present study extended previous
      work by examining the relationship among pain anxiety dimensions, use of active
      and passive coping strategies and arthritis self-efficacy as predictors of
      functional status in 154 rheumatoid arthritis (RA) patients. Functional status
      was assessed using the Five-Factor Model of the Arthritis Impact Scale, 2nd ed.,
      (AIMS2): Physical Functioning, Affective Experience, Symptoms, Social Interaction
      and Role Function. Hierarchical multiple regression analysis on each of the AIMS2
      criterion variables showed that pain anxiety, pain and symptom self-efficacy,
      health status and coping strategies were able to explain between 9 and 38% of the
      variance in the five AIMS2 variables. The present results support the
      hypothesized role of pain anxiety along with previously established contributions
      of self-efficacy and coping strategies, in affecting physical, social, emotional
      and role functioning in chronic RA patients.

PMID- 10957822
TI  - Evaluation of inpatient dialectical-behavioral therapy for borderline personality
      disorder--a prospective study.
AB  - Dialectical-Behavioral Therapy for Borderline Personality Disorder (DBT)
      developed by M. Linehan is specifically designed for the outpatient treatment of
      chronically suicidal patients with borderline personality disorder. Research on
      DBT therapy, its course and its results has focused to date on treatments in an
      outpatient setting. Hypothesizing that the course of therapy could be accelerated
      and improved by an inpatient setting at the beginning of outpatient DBT, we
      developed a treatment program of inpatient therapy for this patient group
      according to the guidelines of DBT. It consists of a three-month inpatient
      treatment prior to long-term outpatient therapy. In this pilot study 24 female
      patients were compared at admission to the hospital, and at one month after
      discharge with respect to psychopathology and frequency of self-injuries.
      Significant improvements in ratings of depression, dissociation, anxiety and
      global stress were found. A highly significant decrease in the number of
      parasuicidal acts was also reported. Analysis of the average effect sizes shows a
      strong effect which prompts the development of a randomized controlled design.

PMID- 10957823
TI  - Relationships between thought-action fusion, thought suppression and obsessive
      compulsive symptoms: a structural equation modeling approach.
AB  - Research has shown that there are strong similarities in content between the
      obsessions and compulsions that characterize obsessive-compulsive disorder and
      nonclinical obsessions and compulsions. However, clinical and nonclinical
      obsessions and compulsions do differ with respect to characteristics like
      frequency, intensity, discomfort and elicited resistance. Two separate concepts
      have been invoked to explain how normal obsessions and compulsions may develop
      into clinical phenomena. First, it is suggested that thought-action fusion (TAF)
      contributes to obsessive-compulsive symptoms. Second, thought suppression may
      intensify obsessive-compulsive symptoms due to its paradoxical effect on
      intrusive thoughts. Although both phenomena have been found to contribute to
      obsessive-compulsive symptoms, possible interactions between these two have never
      been investigated. The current study explored how TAF and thought suppression
      interact in the development of obsessive-compulsive symptoms. Undergraduate
      psychology students (N = 173) completed questionnaires pertaining to TAF, thought
      suppression and obsessive-compulsive symptoms. Covariances between the scores on
      these questionnaires were analyzed by means of structural equation modeling.
      Results suggest that TAF triggers thought suppression, while thought suppression,
      in turn, promotes obsessive-compulsive symptoms.

PMID- 10957824
TI  - Attempting suppression of traumatic memories over extended periods in acute
      stress disorder.
AB  - This study investigated the influence of attempted suppression and thought
      control strategies on traumatic memories. Survivors of civilian trauma with acute
      stress disorder (ASD; n = 20) and without ASD (n = 20) monitored their trauma
      related thoughts for three 24-h periods. In period 1, participants were
      instructed to think about anything. In period 2, participants were administered
      suppression or nonsuppression instructions relating to thoughts of the trauma. In
      period 3, participants were again instructed to think about anything. The results
      revealed no evidence for an increase in trauma-related thoughts following
      suppression instructions. Punishment and worry thought control strategies
      correlated significantly with both anxiety and suppression ratings. Frequency of
      intrusions was associated with a distraction cognitive strategy. These findings
      point to the importance of traumatised individuals' cognitive strategies in
      mediating the management and occurrence of posttraumatic intrusions.

PMID- 10957825
TI  - Dishabituation processes in height fear and dental fear: an indirect test of the
      non-associative model of fear acquisition.
AB  - The fear dishabituation hypothesis described in the non-associative model of fear
      acquisition was tested in a longitudinal birth cohort study. Results were
      consistent with height fear and phobia dishabituation. That is, 're-emergence' of
      a fear of heights occurred between age 11 and 18 years among individuals who
      reported higher levels of non-specific stress at age 15. Interestingly, there was
      no evidence for dental fear dishabituation--a finding consistent with the non
      associative model of fear acquisition. Strengths and weaknesses of the study were
      considered and the results discussed in relation to laboratory-based findings on
      (dis)habituation.

PMID- 10957826
TI  - Processing of phobic stimuli and its relationship to outcome.
AB  - In the present study, we explored factors related to successful treatment outcome
      in a sample of participants with fear of spiders. We specifically examined the
      relationship of general memory, memory for the phobic stimulus, memory for
      anxious responses, and perceived self-efficacy to treatment outcome. Forty-eight
      participants who were afraid of spiders participated in two sessions of in vivo
      exposure therapy. On day 1, participants completed measures of general memory,
      memory for the phobic stimulus, recall of anxiety level during exposure tasks,
      and self-efficacy during exposure tasks. At post-treatment, better memory for
      anxious responses, but not memory for the phobic stimulus, was related to lower
      anticipatory and actual anxiety. Greater self-efficacy, on the other hand, was
      related to better behavioral performance.

PMID- 10957827
TI  - Experimental manipulation of intolerance of uncertainty: a study of a theoretical
      model of worry.
AB  - Intolerance of uncertainty has been identified as an important variable related
      to worry and Generalized Anxiety Disorder (GAD) [Dugas, M. J., Gagnon, F.,
      Ladouceur, R., & Freeston, M. H. (1998). Generalized anxiety disorder: a
      preliminary test of a conceptual model. Behaviour Research and Therapy, 36, 215
      226; Ladouceur, R., Dugas, M. J., Freeston, M. H., Rheaume, J., Blais, F.,
      Boisvert, J.-M., Gagnon, F., & Thibodeau, N. (1999). Specificity of Generalized
      Anxiety Disorder symptoms and processes. Behavior Therapy, 30, 197-207]. The goal
      of the present study was to clarify the relationship between this cognitive
      process and worry by experimentally manipulating intolerance of uncertainty. A
      gambling procedure was used to increase intolerance of uncertainty in one group
      (N = 21) and to decrease intolerance of uncertainty in another group (N = 21).
      The results indicate that participants whose level of intolerance of uncertainty
      was increased showed a higher level of worry, compared to participants whose
      level of intolerance of uncertainty was decreased. These results provide some
      initial clarifications as to the causal nature of the link between intolerance of
      uncertainty and worry. These results are coherent with our theoretical model of
      worry and GAD (Dugas et al., 1998), which stipulates that intolerance of
      uncertainty plays a key role in the acquisition and maintenance of excessive
      worry.

PMID- 10957828
TI  - Discriminant validity of the Social Phobia and Anxiety Inventory (SPAI), the
      Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS).
AB  - Three measures commonly used in assessment of social phobia, the Social Phobia
      and Anxiety Inventory (SPAI [Turner, S. M., Beidel, D. C. & Dancu, C. V. (1996).
      Social phobia and anxiety inventory: manual. Toronto, Ont.: Multi-Health Systems
      Inc.), the Social Phobia Scale (SPS [Mattick, R. P. & Clarke, J. C. (1998).
      Development and validation of measures of social phobia scrutiny fear and social
      interaction anxiety. Behaviour Research and Therapy, 36, 455-470] and the Social
      Interaction Anxiety Scale (SIAS [Mattick, R. P. & Clarke, J. C. (1998).
      Development and validation of measures of social phobia scrutiny fear and social
      interaction anxiety. Behaviour Research and Therapy, 36, 455-470], were compared
      for their ability to discriminate between social phobia and other anxiety
      disorders (panic disorder with or without agoraphobia). Participants were 117
      patients attending a specialized anxiety disorders unit for treatment. While all
      three measures were able to detect differences between social phobic patients and
      patients with panic disorder with or without agoraphobia, a logistic regression
      analysis showed that the SPAI, but not the SPS and SIAS, was a significant
      predictor of membership of the social phobia group. Receiver operating
      characteristic (ROC) analysis also showed that the SPAI was the better measure
      for discriminating between social phobia and panic disorder with and without
      agoraphobia. Analysis of the sensitivity, specificity and positive and negative
      predictive power of the measures at the optimum cutoff scores produced by the ROC
      analysis are presented.

PMID- 10957829
TI  - Reliability and validity of a self-efficacy instrument specific to sickle cell
      disease.
AB  - The psychometric properties of a new, 9-item scale measuring disease-specific
      perceptions of self-efficacy were investigated in a community-based sample of
      adults (N = 83) with sickle cell disease (SCD). The Sickle Cell Self-Efficacy
      Scale (SCSES) was comprised of nine questions relating to participants'
      perceptions of their ability to function on a day-to-day basis and to manage SCD
      symptomatology (e.g. episodes of pain). The SCSES demonstrated good internal
      consistency, discriminant validity, and convergent and predictive validity, both
      with previously validated measures of related constructs as well as with reported
      SCD symptomatology. Overall, the instrument appears to be reliable and valid for
      assessing clients' self-efficacy for engaging successfully in day-to-day
      activities despite having SCD. Future investigators may wish to examine temporal
      and causal links between alterations in self-efficacy and changes in adjustment
      to sickle cell disease; the SCSES provides a psychometrically sound tool with
      which to investigate these phenomena.

PMID- 10957830
TI  - Risk factors for low birth weight in Nepali infants.
AB  - A detailed information on a total of 448 consecutive Nepali births which occurred
      between January 1, 1985 and December 31, 1994 was collected from the birth
      registers of the Khasi-Jaintia Presbetyrian Synod Hospital of Shillong,
      Meghalaya. After the exclusion of still and twin births, and the cases of missing
      information of birth weight, 418 single live births were considered to find out
      the distribution of birth weight and the risk factors of low birth weight (LBW)
      among the Nepali babies of this state. The incidence of LBW was 21.53%. The
      results of univariate analysis revealed that sex, maternal age, parity, gestation
      period, economic condition and maternal education were significantly related to
      the incidence of LBW. Multiple logistic regression analysis revealed that all the
      above mentioned factors had independent risk for LBW except the economic
      condition and father's education. Thus, the present results suggest conducting
      further studies among other ethnic groups of North-East India to understand the
      problem of LBW at the population level which may help to formulate an effective
      maternal and child health care program in this region.

PMID- 10957831
TI  - Food security among preschool children.
AB  - A cross-sectional study of preschool children from 450 families from a
      residential colony of 'D' class hospital employees was undertaken to study food
      security & associated variables. Food security was established from (a) 24 hours
      recall method with 1 day weighment and (b) monthly food purchase inventory for
      cereals and pulses. Relationship between food secure status and variables of
      interest was studied from Chi-square value and odds ratio. Only 42.6% households
      and 54% preschool children from these households were calorically secure.
      Insecurity was the highest in 48-59 months age group. Per capital income,
      increasing birth order, family size, household size, less years of schooling of
      the mother, less than 4 meals per day and pulse insufficiency at home were
      associated with food insecurity. Per capita income ensures food availability at
      home. Family size and household size probably ensure distribution. Mother's
      education, frequent feeds more than four, ensure that it reaches the preschool
      children.

PMID- 10957832
TI  - Non-sucrose sweetener for pain relief in sick newborns.
AB  - A prospective controlled blind study was carried out in the Special Care Unit for
      Newborns to assess the effect of commercially available sweetener on pain relief
      in newborns. Response to intramuscular injection and the pain stimulus was
      studied in twenty-five sick newborns, 13 preterm and 12 term, in a blinded
      fashion. Pain score, duration of cry, heart rate and oxygen saturations were
      studied. Basal response, responses with sterile water or sweetener were recorded
      in each baby. Responses to sweetener versus no solution and sweetener versus
      sterile water were compared by applying paired t-test. The reduction in pain
      score with sweetener was significant when compared with no solution. The
      difference was not significant when compared with sterile water. Similarly,
      duration of cry and heart rate with sweetener were significantly less when
      compared to sterile water or to no solution. However, the difference in oxygen
      saturation was not significantly different. Sweetener has an analgesic effect in
      sick babies. This can minimise adverse effects associated with painful
      procedures.

PMID- 10957833
TI  - Knowledge, attitude and practices about neonatal hypothermia among medical and
      paramedical staff.
AB  - The present study was undertaken to evaluate the knowledge, attitude and
      practices about neonatal hypothermia among medical and paramedical staff dealing
      with newborn care. A total of 160 subjects were assessed (40 pediatric medicine
      residents, 40 obstetric residents, 40 private practitioners and 40 paramedical
      staff working in labor room and postnatal wards) A pre-tested structured
      questionnaire was used. Only 47.8% of the subjects defined neonatal hypothermia
      correctly. As many as 52.2% of the interviewees considered it to be an uncommon
      problem. Lethargy, refusal for feed and cold to touch were mentioned as common
      symptoms of neonatal hypothermia by 97.5%, 80% and 77.5% of the respondents
      respectively. Decreased body temperature, cyanosis, apnea and edema of feet were
      found as common signs. Only 18.6% of the interviewees had knowledge about correct
      method of recording the temperature in a newborn. The present study reveals the
      gross lacunae in the knowledge regarding various aspects of neonatal hypothermia
      among pediatric and obstetric residents and paramedical staff working in labor
      room and postnatal wards. To reduce the neonatal morbidity and mortality due to
      neonatal hypothermia, greater emphasis should be laid on this problem while
      designing curriculum for training of undergraduate and postgraduate doctors,
      paramedical staff and traditional birth attendants.

PMID- 10957835
TI  - Dengue haemorrhagic fever in Sri Lanka.
AB  - This is a retrospective study of 354 suspected cases of dengue haemorrhagic fever
      (DHF), admitted to Lady Ridgeway Hospital (LRH), Colombo during 1996. The
      objective of the study was to determine the correlation between clinical,
      laboratory, radiological and serological diagnosis of DHF. Diagnosis was based on
      the haemagglutination inhibition test. Serologically, 177 cases had dengue
      infection and, of these, 143 children had DHF. There was only a 50% correlation
      between clinical suspicion of DHF and positive serology. There was 100%
      correlation between laboratory and radiological diagnosis of DHF and positive
      serology.

PMID- 10957834
TI  - Glycogen storage disease type Ia: frequency and clinical course in Turkish
      children.
AB  - The aim of this study was to determine the relative frequency of type Ia in
      glycogen storage disease (GSD) with prominent liver involvement and to determine
      its clinical and laboratory findings and prognosis in Turkish children. From 1980
      to 1998, 45 out of 100 GSD patients (27 male) with liver involvement had been
      diagnosed for type Ia. The files were retrospectively evaluated and clinical and
      laboratory features were documented. In addition to routine laboratory
      evaluations, urine albumin, calcium excretions, and plasma biotinidase activity
      were measured. Breast-feeding was continued in all infants. After 6 months of
      age, uncooked cornstarch was administered to the patients. The relative frequency
      of type Ia in GSD with liver involvement was 45%. The diagnosis was made in 71%
      of patients before 2 years of age (median 1 year). Main complaint was abdominal
      protruding (57.8%), and main physical finding was hepatomegaly (100%). Forty
      percent of the patients had growth retardation at diagnosis. Among laboratory
      parameters, hypertriglyceridemia (97.8%) and hypertransaminasemia (95.6%) were
      the most frequent findings following plasma biotinidase activity, which was
      elevated in all patients. Microalbuminuria was determined in 52.8% of the
      patients and hypercalciuria in 23.8%. Histopathological findings of the liver
      included fibrosis (75.6%), steatosis (37.8%), mosaicism (24.4%) and nuclear
      hyperglycogenation (15.6%). During follow-up period, the ratio of patients with
      growth retardation did not change. Transaminases were decreased in 48.7% of the
      patients. Although triglyceride and cholesterol levels decreased in the majority
      of the patients, they did not normalise. The prevalence of type Ia in GSD with
      prominent liver involvement was found higher than the other reports.
      Microalbuminuria was also higher than the previous reports.

PMID- 10957836
TI  - Interventional pediatric cardiology: device closures.
AB  - Surgical treatment of various septal defects has been long established. With the
      advances in transcatheter therapy dilatation techniques for valvular stenosis and
      vascular obstruction have become established procedures. Closure of septal
      defects in the catheterization laboratory has also been introduced; some of these
      have come into regular use in current practice. In 1967, Porstmann et al reported
      the use of Ivalon plug to close patent ductus arteriosus (PDA). Since then,
      several devices have been used including Rashkind PDA ocluder (not being used
      now), Gianturco coils, detachable coils (for small PDA), CardioSEAL and other
      umbrella devices and Amplatzer PDA occluder. Closure rates vary from 95-98% in
      most series, however, some of these devices are very expensive, more so, when
      compared to the cost of surgical ligation of PDA. Catheter closure of secundum
      atrial septal defect (ASD) has also been done by various devices like clamshell
      device, Sideris Buttoned device, ASDOS device, Amplatzer device and cardioSEAL.
      So far no device has been accepted as ideal for every case, however, Amplatzer
      device has been used most extensively. Issues such as completeness of
      endothelialisation, incidence of late arrhythmias, endocarditis remain uncertain.
      However, in select population of ASD cases with a central secundum defect, device
      closure is being used increasingly. Device closure of ventricular septal defect
      remains challenging and controversial and is probably available to a small group
      of children with defects that are difficult to close surgically and involve
      higher risk.

PMID- 10957837
TI  - Fetal echocardiography.
AB  - Since the first report of fetal echocardiography in 1972 by Winsberg, several
      advances in ultrasound technology have occurred allowing detailed evaluation of
      cardiac anatomy in the second trimester fetus. Fetal echo is indicated in high
      risk pregnancies where the chances of fetus having a congenital heart disease
      (CHD) are likely to be high e.g., in fetus with extracardiac anomalies picked up
      on obstetric ultrasound, those with a history of CHD in family, maternal diabetes
      (especially insulin dependent), maternal connective tissue disorder etc. The
      reported sensitivity of fetal echo has ranged from 4-96% in various series
      depending upon the equipment, level of training, study design and examination
      technique. Although many CHD can be detected in four chamber view, an important
      group malformations that would need early intervention are likely to be missed.
      Hence a detailed echocardiographic examination including the outflow views must
      be done. Defects like atrial septal defect and patent ductus arteriosus cannot be
      diagnosed in fetal echo, as these are part of normal fetal physiology. Other CHD
      like coarctation of aorta, small ventricular septal defects, mild valvular
      stenosis, partial anomalous pulmonary venous drainage are also difficult to
      diagnose. Ultrasound assessment of fetus, however, has a clear role in the
      diagnosis, monitoring and management of fetuses with sustained arrhythmias.
      Prenatal diagnosis of CHD helps in planning the optimal management of the baby
      e.g. a fetus with a ductus dependent lesion can be planned to be delivered in a
      tertially care centre for stabilisation and early initiation of prostaglandin
      therapy to avoid acidosis and organ damage. Future of fetal medicine lies in
      fetal cardiac surgery for which echocardiography will play a very important role.

PMID- 10957838
TI  - Diagnosis and management of primary pulmonary hypertension.
AB  - Pulmonary arterial hypertension in children can occur secondary to shunt lesion
      like ventricular septal defect, patent ductus arteriosus or it may be idiopathic,
      the so-called primary pulmonary hypertension (PPH). The progression of PPH is
      usually rapid in children as compared to adults and the mean survival is 2-3
      years after the diagnosis is made. Histological changes in the form of medical
      muscular hypertrophy, intinal hyperplasia and later angiornatous, plexiform
      lesions occur in pulmonary vasculature. The pulmonary vasculature normally is a
      high flow, low resistance circuit and allows large blood flow without marked
      increase in pulmonary arterial pressure. However, with prolonged increased flow
      or any other vasoconstrictor stimulus, histological changes start occurring in
      the pulmonary bed resulting in increasing pressure in pulmonary artery. Right
      ventricular hypertension follows resulting in right ventricular hypertrophy and
      later dysfunction. Life threatening arrhythmias may result in sudden death in
      some of these patients. Clinical presentation is in the form of exertional
      dyspnoea with syncope at times. Over 50% of children with PPH are helped by
      vasodilators. They may be treated with calcium channel blockers (e.g. nifedipine,
      dose titrated to blood pressure) orally. Those not responding to oral
      vasodilators can be put on chronic inhaled nitric oxide or continuous intravenous
      prostacyclin infusion. Chronic anticoagulation therapy may also increase
      survival. In symptomatic cases, blade/balloon atrial septostomy may increase
      survival in patients of PPH with intact atrial sptum. For children not responding
      to medical therapy, lung transplantation may be the answer in near future.

PMID- 10957839
TI  - Cardiac abnormalities in birth asphyxia.
AB  - Cardiac abnormalities in birth asphyxia were first recognised in the 1970s. These
      include (i) transient tricuspid regurgitation which is the commonest cause of a
      systolic murmur in a newborn and tends to disappear without any treatment unless
      it is associated with transient myocardial ischemia or primary pulmonary
      hypertension of the newborn (ii) transient mitral regurgitation which is much
      less common and is often a part of transient myocardial ischemia, at times with
      reduced left ventricular function and, therefore, requires treatment in the form
      of inotropic and ventilatory support (iii) transient myocardial ischemia (TMI) of
      the newborn. This should be suspected in any baby with asphyxia, respiratory
      distress and poor pulses, especially if a murmur is audible. It is of five types
      (A to E) according to Rowe's classification. Type B is the most severe with
      respiratory distress, congestive heart failure and shock. Echocardiography helps
      to rule out critical left ventricular obstructive lesions like hypoplastic left
      heart syndrome or critical aortic stenosis. ECG is very important for diagnosis
      of TMI, and may show changes ranging from T wave inversion in one lead to a
      classical segmental infarction pattern with abnormal q waves. CPK-MB may rise and
      echocardiogram shows impaired left ventricular function, mitral and/or tricuspid
      regurgitation, and at times, wall motion abnormalities of left ventricle.
      Ejection fraction is often depressed and is a useful marker of severity and
      prognosis. Treatment includes fluid restriction, inotropic support, diuretics and
      ventilatory resistance if required (v) persistent pulmonary hypertension of the
      newborn (PPHN). Persistent hypoxia sometimes results in persistence of
      constricted fetal pulmonary vascular bed causing pulmonary arterial hypertension
      with consequent right to left shunt across patent ductus arteriosus and foramen
      ovale. This causes respiratory tension and right ventricular failure with
      systolic murmur of tricuspid, and at times, mitral regurgitation. Treatment
      consists of oxygen and general care for mild cases, ventilatory support, ECMO and
      nitric oxide for severe cases. Cardiac abnormalities in asphyxiated neonates are
      often underdiagnosed and require a high index of suspicion. ECG and Echo help in
      early recognition and hence better management of these cases.

PMID- 10957840
TI  - Surgical therapy for the univentricular heart.
AB  - The natural history of the univentricular physiology is determined primarily by
      the presence (severity) or absence of obstruction to pulmonary blood flow and
      secondarily by the single ventricular cardiomyopathy that develops in response to
      chronic volume overload. Important obstruction to pulmonary blood flow will
      affect survival because of severe hypoxia and may necessitate surgical treatment
      (systemic to pulmonary artery shunt or cavopulmonary shunt depending on the age
      of the patient and a host of other factors). In the absence of significant
      obstruction to pulmonary blood flow, the symptomatology is one of congestive
      heart failure with later development of irreversible pulmonary vascular disease.
      In this situation, a pulmonary artery band is indicated to limit pulmonary blood
      flow and reduce pulmonary artery pressures to acceptable levels. Even in the
      presence of significant limitation of pulmonary blood flow, the single ventricle
      is a volume-loaded ventricle as it receives both pulmonary and systemic venous
      return. Chronic volume overload and persistent hypoxia is detrimental to
      ventricular function and gradually lead to the development of atrioventricular
      valve incompetence. Complete separation of oxygenated and deoxygenated blood may
      be obtained by ventricular septation in suitable cases (beyond the scope of this
      presentation) or by systemic venous diversion to the pulmonary (the Fontan
      circulation) arteries thus achieving complete oxygenation simultaneous with
      abolition of any recirculation.

PMID- 10957841
TI  - Haemolytic anaemia secondary to vitamin E deficiency in premature infants.

PMID- 10957842
TI  - Rett syndrome.
AB  - Rett syndrome is a progressive neurodegenerative disease of unknown etiology.
      Reported here are three children who presented with all clinical features of Rett
      syndrome. The aim of this presentation is to alert physicians to the existence of
      this progressive brain disease which only affects girls and so far no specific
      treatment has been suggested.

PMID- 10957843
TI  - Type I hyperprolinemia.
AB  - Type I hyperprolinemia is an autosomal recessive disorder characterized by
      increased plasma and urine proline concentrations due to a deficiency of the
      enzyme, proline oxidase. This rare inborn error of proline metabolism is
      generally believed to be a benign condition although many associated clinical
      abnormalities have been reported. We report two siblings with Type I
      hyperprolinemia who presented with recurrent seizures. They had elevated plasma
      proline levels with massive prolinuria without an increased urinary excretion of
      delta 1-pyrolline-carboxylic acid.

PMID- 10957844
TI  - Perinephric abscess due to Aspergillus fumigatus.
AB  - Invasive aspergillosis is rare in healthy children. Severe systemic complications
      due to aspergillosis may be seen in AIDS patients with severe neutropenia and
      macrophage dysfunction.

PMID- 10957846
TI  - Analysis of physiochemical properties on the sand.

PMID- 10957845
TI  - Surveillance at US military installations for bioterrorist and emerging
      infectious disease threats.

PMID- 10957847
TI  - Domestic swine model for the assessment of chemical warfare agent-anesthetic
      interactions: some effects of sulfur mustard.
AB  - A domestic swine model was developed to examine the interaction of chemical
      warfare agents with anesthetics and other drugs used during general anesthesia.
      Animals were fully instrumented, and clinically relevant physiological parameters
      were monitored throughout the experimental procedures. Exposure of animals under
      halothane anesthesia to the chemical warfare agent sulfur mustard (HD; 1 mg/kg
      intravenous) produced mild signs of systemic intoxication during the subsequent 5
      hours. Induction doses of ketamine 1 hour after HD exposure resulted in periods
      of profound apnea, with continued respiratory distress for the next 2 hours. When
      animals were treated with HD 1 hour after the initiation of ketamine anesthesia,
      severe and persistent convulsion-like muscular activity was observed within 45
      minutes of HD administration. This nonpurposeful activity was not ameliorated by
      diazepam but was dramatically reduced or eliminated by resumption of halothane
      anesthesia. Treatment of HD-intoxicated pigs with succinylcholine produced a
      prolonged apnea resulting in death. In these apparently mildly HD-intoxicated
      animals, the introduction of ketamine or succinylcholine can rapidly induce
      potentially life-threatening situations.

PMID- 10957848
TI  - Telemedicine improved diabetic management.
AB  - Effective control of diabetes is known to delay or prevent the end-organ
      complications of this disease. Can telemedicine improve a patient's ability to
      self-manage diabetes? Twenty-eight patients entered a study comparing home
      telemedicine consultation with standard outpatient care. A nurse case manager
      contacted the telemedicine group once a week under the direction of a primary
      care physician, who contacted the telemedicine group once a month. Laboratory
      studies and total body weight were measured at the beginning and at the end of
      the 3-month study. The hemoglobin A1c (HbA1c) and total body weight improved
      significantly in the intervention (telemedicine) group, as shown by a 16%
      reduction in mean HbA1c level (from 9.5 to 8.2%) and a 4% mean weight reduction
      (from 214.3 to 206.7 pounds). Based on our experience, we present a functionally
      based telemedicine classification system to improve the application of electronic
      medicine in future studies.

PMID- 10957849
TI  - Access and late-stage diagnosis of breast cancer in the military health system.
AB  - The results reported in this paper are from a larger study examining the
      relationship between access and stage at diagnosis of breast cancer in African
      American and white women. This paper focuses on the results describing the extent
      to which potential and realized access predict stage at diagnosis within an equal
      economic access health care system. Data in this descriptive-comparative study
      were collected through secondary analysis using the tumor registry records of 62
      African-American and 573 white women diagnosed with breast cancer in the military
      health system between January 1, 1988, and December 31, 1997. Logistic regression
      analysis revealed that late-stage breast cancer was more likely to be diagnosed
      in African-American women from low socioeconomic strata with incidental breast
      self-examination-discovered cancers. The most significant predictors of late
      stage diagnosis were means of discovery and the length of time between discovery
      and diagnosis.

PMID- 10957850
TI  - Meibomian gland status comparison between active duty personnel and U.S.
      veterans.
AB  - PURPOSE: To evaluate the lid and meibomian gland status of active duty forces
      (ADF) and U.S. veterans (USV) to compare the prevalence of lid dysfunction and
      disease in each population. METHODS: One examiner observed 113 consecutive
      patients in both groups during a 2-week period at two federal service optometry
      clinics. All eyes were graded with regard to negative findings (or normal),
      meibomian gland dysfunction (MGD), and/or meibomitis from an established
      criterion. RESULTS: 90.3% of ADF had normal lid findings, 5.3% of ADF had MGD
      (all contact lens patients), and 4.4% of ADF had meibomitis; 28.9% of USV had
      normal findings, and 71.1% of USV had MGD or meibomitis (no patients wore contact
      lenses). CONCLUSION: Our findings reveal that a definite difference exists
      between ADF personnel and USV in eyelid physiology and pathophysiology. This
      difference should be noted by the clinician who evaluates such patients. This
      will affect the differential diagnosis of ocular symptomatology in the contact
      lens and non-contact lens patient.

PMID- 10957851
TI  - Air Force Dental Service commemorates golden anniversary, 1949 to 1999.
AB  - For 50 years, evolving from aviation dentistry to aerospace dentistry, the U.S.
      Air Force Dental Service has successfully met the challenge of supporting the
      mission of the Air Force as well as made significant contributions to the
      profession of dentistry. This commemorative article not only highlights its
      achievements but serves as an historical tribute to the Dental Service's past of
      honoring the mission of the Air Force.

PMID- 10957852
TI  - Put more "bite" into health promotion: a campaign to revitalize health promotion
      in the Army Dental Care System. Part I. The mouthguard, sealant, and nursing
      caries initiatives.
AB  - During the course of 1998, the Army Dental Care System launched "Put More 'Bite'
      into Health Promotion," a campaign to revitalize health promotion in the Army
      Dental Care System. In this paper, we discuss the content, rationale, and
      evidence base for three of five health promotion initiatives that are part of the
      campaign: mouthguard fabrication and counseling, sealant placement and education,
      and nursing caries education.

PMID- 10957853
TI  - Dental health promotion and preventive dentistry practices of U.S. Army dentists.
AB  - In May 1997, all Army dentists assigned full-time to clinical duties (1,100) were
      sent a mail survey that queried how often they deliver dental health promotion
      and preventive dentistry services and the type and source of their patient
      educational materials. By August, 606 dentists had responded. Simple frequencies
      were generated using SPSS. Results show that tobacco, oral hygiene, and
      periodontal counseling and oral cancer and blood pressure screening are delivered
      frequently, whereas nursing caries, mouthguard, sealant, and nutrition services
      are delivered infrequently. Army dentists relied almost exclusively on oral
      presentations to deliver health promotion messages. Few used more than one source
      for health promotion materials. These results suggest that the delivery of dental
      health promotion and preventive dentistry services in the Army is suboptimal. A
      campaign to heighten provider awareness of the importance of delivering these
      services should be launched. The campaign should also teach providers how to make
      their health promotion efforts maximally effective through the application of
      proven health marketing techniques.

PMID- 10957854
TI  - The impact of physician training on child maltreatment reporting: a multi
      specialty study.
AB  - BACKGROUND: Past studies have suggested that physicians underreport suspected
      child maltreatment (CM) cases, possibly because of a lack of knowledge of the
      subject. OBJECTIVES: To evaluate the amount, format, and content of CM training
      received in residency (graduate medical education) and continuing medical
      education (CME), and to compare its relationship to the likelihood of reporting
      CM. METHODS: A total of 482 U.S. Air Force emergency physicians, family practice
      physicians, and pediatricians were surveyed regarding the amount/type of CM
      training received as well as their CM reporting practices. RESULTS: Pediatricians
      report receiving more CM training during CME than either emergency physicians or
      family practice physicians, whereas during residency, both pediatricians and
      emergency physicians received more training than family practice physicians. Two
      thirds of the training related solely to physical and sexual abuse, with little
      attention paid to other forms of CM. Regression analysis indicated that the only
      factor associated with the likelihood of reporting maltreatment was the amount of
      CME received. CONCLUSION: CME seems to positively influence physician reporting
      practices for CM cases, suggesting a need for universal training protocols.

PMID- 10957855
TI  - Military duty: risk factor for preterm labor? A review.
AB  - The female military population represents a high-risk group for preterm labor and
      other adverse pregnancy outcomes. As the number of women entering the armed
      forces continues to increase, concerns regarding the effects of military service
      on pregnancy must persist. Although active duty females have access to prenatal
      care and maintain consistent follow-up, previous research has noted a 5-fold
      increase in preterm labor compared with civilian working women. Hospitalization
      and loss of work attributable to pregnancy complications directly affect
      productivity and mission accomplishment; therefore, it is crucial to identify
      those at risk to institute measures that will prevent such occurrences and
      decrease time away from work. This article provides a review of the existing
      literature concerning preterm labor in military women, comparisons with the
      civilian population, and recommendations for future research.

PMID- 10957856
TI  - Evaluation of an early discharge program for infants after childbirth in a
      military population.
AB  - The objective of this study was to evaluate the outcome of an early discharge
      program for infants with regard to length of stay, patient safety, maternal
      satisfaction, and hospital expense in a military population. The study consisted
      of a retrospective analysis of data from two 6-month periods--March to August
      1994 (before early discharge) and March to August 1996 (after early discharge)-
      in a military, tertiary care, teaching hospital. The criteria for early discharge
      included healthy term singleton newborns delivered by uncomplicated vaginal
      delivery with maternal support systems, transportation, and phone access. The
      interventions included maternal education regarding maternal and infant care and
      telephone follow-up at 48 hours and 5 days after discharge. The main outcome
      measures included length of hospital stay, inpatient cost, infant health services
      utilization, and maternal satisfaction (measured by survey). During the 6-month
      study periods in 1994 and 1996, a total of 1,911 deliveries were examined. The
      mean number (+/- SD) of hospital days per infant was 2.54 +/- 0.83 in 1994
      compared with 1.88 +/- 1.03 in 1996. There was not a statistically significant
      difference in the number of readmissions between 1994 (9 of 1042, 0.86%) and 1996
      (12 of 869, 1.38%) (odds ratio = 1.61, 95% confidence interval = 0.67, 3.83). A
      review of the infant health services utilization revealed a statistically
      significant increase in the total number of clinic visits (scheduled and
      unscheduled) before the 2-week well-child visit for the 1996 group. However, that
      group did not experience a change in the number of emergency room visits. Seventy
      five percent of mothers were satisfied with the program as assessed by
      questionnaire. In addition, the program was able to save 599 inpatient hospital
      days, for a total cost savings of $442,903.23 in 1996. This reduction in
      inpatient hospital days netted an average cost savings of $509.67 per infant. By
      following strict discharge criteria, increasing parent education before
      discharge, implementing a phone follow-up system, and ensuring easy access to
      care, an early discharge program in our military population was not associated
      with increased adverse newborn outcomes and reduced costs.

PMID- 10957857
TI  - Veterans have less age-related cognitive decline.
AB  - Military service involves exposure to a number of stresses, both psychological
      and physical. On the other hand, military personnel generally maintain excellent
      fitness, and veterans have increased access to education and health care. The
      overall effect on age-related cognitive decline, whether for good or ill, of
      having served in the armed forces has not been investigated previously. In this
      study, we examined a diverse population of 208 veterans and 1,216 civilians
      followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and
      1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score
      after a median of 11.5 years. Veterans were found to have significantly less
      decrease in MMSE scores at follow-up even after sex, race, and education were
      taken into account. These results suggest an overall positive effect of military
      service on the rate of age-related cognitive decline.

PMID- 10957858
TI  - Diazepam replacement.

PMID- 10957859
TI  - A procedure for the rapid detection of depleted uranium in metal shrapnel
      fragments.
AB  - Depleted uranium is now widely used in the armor of military vehicles as well as
      in kinetic-energy penetrators designed to defeat enemy armor. As a result, the
      potential that personnel will be wounded by depleted uranium fragments has
      increased. Because toxicities associated with depleted uranium fragments may
      ultimately require different treatment protocols than those used for traditional
      metal fragment injuries, a method to rapidly detect the presence of depleted
      uranium in surgically excised shrapnel fragments is required. By treating the
      shrapnel fragment with an extracting agent, such as nitric acid, for 5 minutes in
      an ultrasonic cleaner, sufficient metal is solubilized to allow for colorimetric
      detection using a pyridylazo dye. Although several metals are capable of being
      detected under these conditions, the reaction can be made specific for depleted
      uranium through the use of masking agents such as sodium citrate and
      ethylenediaminetetraacetic acid. This procedure allows for the rapid (< 15
      minutes) extraction and detection of depleted uranium in metal shrapnel
      fragments.

PMID- 10957860
TI  - Risk factors for sarcoidosis hospitalization among U.S. Navy and Marine Corps
      personnel, 1981 to 1995.
AB  - Sarcoidosis has been associated with various demographic risk factors, yet
      findings may be falsely influenced by effects such as socioeconomic status. We
      used univariate and multiple logistic regression to compare demographic data from
      military sarcoidosis hospitalizations with similar data from the general military
      population from 1981 to 1995. A total of 626 first hospitalizations for
      sarcoidosis were identified. After adjusting for pay grade, blacks had seven-fold
      increased odds of sarcoidosis hospitalization compared with whites. The oldest
      age group had five times the odds of the youngest age group. A southeastern
      United States home of record was associated with increased risk. Multivariate
      modeling permitted us to determine independent risk factors for sarcoidosis
      hospitalization, in contrast to previous studies that focused mainly on
      unadjusted rates. These findings are useful in identifying populations at high
      risk for sarcoidosis.

PMID- 10957861
TI  - Family practice career attrition, 1969 to 1993: a comparison of 336 civilian and
      military graduates of one medical school.
AB  - Instability of specialty choice and career after initial residency entry will
      affect health personnel projections. Military physicians may differ from civilian
      physicians in their specialty choice behaviors during their careers. A cohort of
      336 graduates who chose family medicine residency training was identified from
      the graduating classes of 1969 through 1993 at a large private medical school.
      Current specialty identification was determined, and attrition from family
      medicine was computed. As of 1997, 275 graduates (82%) were still in family
      medicine careers, defined by American Academy of Family Physicians membership or
      current American Board of Family Practice certification. Of graduates who entered
      military programs, 22 of 77 (28%) had left family medicine careers; 39 of 259
      (15%) of the graduates who entered civilian programs had left. This difference
      was statistically significant (p = 0.007). Family medicine career retention is
      lower for males in military programs compared with males in civilian programs or
      females in military programs.

PMID- 10957862
TI  - Stevens-Johnson syndrome after erythromycin therapy while deployed at sea.
AB  - Stevens-Johnson syndrome is a cutaneous reaction pattern that represents the
      progression of symptoms of erythema multiforme. These reactions can range from
      mild (EM minor) to severe (EM major) and even life-threatening (Stevens-Johnson
      syndrome or toxic epidermal necrolysis). The difference between Stevens-Johnson
      syndrome and toxic epidermal necrolysis is the percentage of body surface area
      involved; toxic epidermal necrolysis involves widespread skin necrosis and
      bullous formation with epidermal detachment resembling scalded skin. The three
      most common triggers for Stevens-Johnson syndrome are herpes simplex infection,
      Mycoplasma infection, and drug reactions. This is a case of Stevens-Johnson
      syndrome occurring after erythromycin treatment aboard an aircraft carrier while
      deployed at sea in the Persian Gulf.

PMID- 10957863
TI  - Lemierre syndrome: magnetic resonance imaging and computed tomographic
      appearance.
AB  - Lemierre syndrome consists of septic thrombophlebitis of the internal jugular
      vein secondary to oropharyngeal infection, usually with Fusobacterium
      necrophorum. Septic metastatic emboli and distant infection are characteristic.
      We describe the imaging appearance of Lemierre syndrome in an adolescent female
      by both magnetic resonance imaging and computed tomography. This case illustrates
      the rapid onset and characteristic progression of the rare syndrome of Lemierre.
      In addition, we used magnetic resonance imaging to effectively distinguish
      between inflammatory venous thrombosis and abscess, thus avoiding surgery in our
      patient. Early directed antibiotic therapy is mandatory to ensure good outcome.

PMID- 10957864
TI  - Births: preliminary data for 1999.
AB  - OBJECTIVES: This report presents preliminary data for 1999 on births in the
      United States. U.S. data on births are shown by age, race, and Hispanic origin of
      mother. Data on marital status, prenatal care, cesarean delivery, and low
      birthweight are also presented. METHODS: Data in this report are based on more
      than a 97-percent sample of births for 1999. The records are weighted to
      independent control counts of births received in State vital statistics offices
      in 1999. Comparisons are made with 1998 final data. RESULTS: The crude birth rate
      in 1999 was 14.5 per 1,000 population, a slight decline from 1998 (14.6),
      returning to the level observed in 1997. However, the fertility rate, which is
      limited to women aged 15-44 years, was 65.8 in 1999, a slight increase over the
      rate for 1998 (65.6). The birth rate for teenagers continued to decline for 1998
      99, dropping 3 percent to 49.6 births per 1,000 females aged 15-19 years. The
      1999 rate for teenagers is 20 percent lower than the recent high point in 1991.
      The rate for young teenagers 15-17 years fell 6 percent, and the rate for
      teenagers 18-19 years declined 2 percent. Since 1991, rates have fallen 26
      percent for teenagers 15-17 years, and 15 percent for teenagers 18-19 years.
      Birth rates for women aged 20-24 years declined slightly between 1998 and 1999
      whereas the rate for women aged 25-29 years rose 2 percent. Birth rates for women
      in their thirties and forties continued their long increase. Rates for women in
      their thirties increased 2 to 3 percent and were the highest in three decades.
      The birth rate for women aged 40-44 years was the highest level reported since
      1970. The birth rate for unmarried women in 1999 was 43.9 per 1,000, 1 percent
      lower than in 1998 and 6 percent lower than the peak level reported for 1994
      (46.9). However, the number of births to unmarried women was up about 1 percent
      due to the continued increase in the number of unmarried women of childbearing
      age. The rate of prenatal care utilization continued to improve. The total
      cesarean rate increased 4 percent between 1998 and 1999 and continued a 3-year
      rise. The low birthweight rate remained unchanged at 7.6 percent.

PMID- 10957865
TI  - [Evidence-based radiotherapy in the treatment of operable breast cancer: results
      in the 1990-ies].
AB  - The aim of this study was to give information about the evidence based radiation
      oncology in the treatment of operable breast cancer for specialists involved in
      the national public health. It was performed a review of the English language
      clinical studies published in the nineties, in which specific radiotherapy
      questions of operable breast cancer were debated. Clinical studies were
      classified according to the level of obtained evidence: randomized study (level
      I.), cohort study (level II.), retrospective study (level III.) and meta-analysis
      (mathematical synthesis of results). 1. Findings of one large randomized study
      indicate that lumpectomy plus irradiation is more beneficial than lumpectomy
      alone for women with ductal carcinoma in situ. Findings are supported by
      retrospective studies. 2. There are four complete published randomized studies
      comparing the outcome of conservative surgery alone to that of conservative
      surgery plus radiation for patients with stage I-II. breast cancer. The local
      recurrence rate is unacceptably high when random patients are treated without
      radiotherapy. Meta-analysis of these studies conferred statistically significant
      survival advantages on women receiving irradiation. In one randomized clinical
      trial the delivery of a 10 Gy boost to the tumor bed after 50 Gy to the whole
      breast significantly reduces the risk of early local recurrence. Additional
      follow-up evaluation and more evidence will be required to define the indications
      for boost irradiation. In one randomized trial with unselected patients there was
      a significant superiority in local control for whole breast irradiation compared
      to partial breast irradiation, but interim results of prospective studies with
      carefully selected women appear promising. 3. Findings of three randomized
      controlled clinical trials indicate that postmastectomy radiotherapy reduces
      mortality from breast cancer by preventing locoregional recurrences in node
      positive patients. One study examined the effect of radiation on overall survival
      by meta-analysis of earlier published randomized studies and demonstrated the
      reduction of breast cancer deaths in irradiated patients. 4. The value of
      irradiation of parasternal lymph nodes is uncertain by retrospective studies and
      is currently being studied in a large European randomized trial. After an
      adequate axillary lymphadenectomy the incidence of axillary recurrence is low and
      there is no indication for irradiation. Results of two retrospective studies
      indicate that irradiation of supraclavicular lymph nodes is beneficial in
      patients with four or more positive axillary lymph nodes. In summary, thank to
      the intensive clinical research in radiotherapy, the irradiation of patients with
      operable breast cancer is based on level I. scientific evidences in the majority
      of the cases. Results of randomized controlled clinical trials and meta-analyses
      indicate that radiotherapy is more than locoregional control: breast cancer
      deaths are reduced among irradiated patients.

PMID- 10957866
TI  - [Hepatocyte proliferation and DNA content in chronic hepatitis C].
AB  - Apart from inflammatory reaction, the death of hepatocytes is also a
      characteristic of chronic hepatitis. Necroinflammation is followed by
      compensatory proliferation, which plays a rather important role in maintaining
      the liver function. Authors studied the DNA content of hepatocytes in patients
      with chronic hepatitis C, and determined the ratio of hepatocytes in phases G1, S
      and G2 to determine the hepatocyte proliferation and regeneration capacity of the
      liver. Liver biopsy samples were taken from 23 patients with chronic hepatitis C
      and from 16 with chronic hepatitis with non viral origin, from which nuclear
      suspension counts were done based on the histological slides. A total of 16
      normal liver tissue samples served as control. The DNA index, G1, S, G2 and
      polyploid fraction were determined using the DNACE (Digital Image Analyzer for
      Nuclear Deoxyribonucleic Acid Content Estimation, KFKI/NIO, Hungary) digital
      imaging process. The DNA index was found to be significantly higher in the
      chronic hepatitis C than in the non-C group, with the verification of aneuploidy
      (DI > 1.10). The chronic non-C hepatitis cases showed lower G1 (88 +/- 6) and
      higher S (7.8 +/- 6.6) fractions. In comparison to the normal liver tissues, the
      chronic hepatitis C cases also revealed a significantly (p < 0.05) lower G1 (91
      +/- 5) and a higher S (5.4 +/- 3.6) fraction, though staying behind the values
      found for the non-viral group. The deviation can be explained by the presentation
      of the HCV proliferation inhibitory effect. The polyploid cell fraction revealed
      a significantly higher value in the chronic non-viral cases as compared to the C
      virus group, reflecting on the decreased regeneration capacity of the liver. When
      comparing the HCV groups, significant differences were found between the mild and
      moderate cases in respect to the G1 and G2 fractions. At the same time, the
      moderate and severe cases showed statistical deviation regarding the DNA index.
      Chronic hepatitis C virus infection reduces the proliferation of hepatocytes and
      the regeneration capacity of the liver. The aneuploid DNA index reflects on
      genetic instability, which could be the basis of the malignant transformation of
      the cells.

PMID- 10957867
TI  - [The role and value of urodynamics in the follow-up of children with  surgical
      bladder augmentation and substitution].
AB  - The authors investigated postoperative capacity, compliance of the urinary
      bladder and urinary continence in children who underwent bladder augmentation
      and/or bladder substitution for various forms of urinary incontinence. In 20
      children, bladder augmentation and/or bladder substitution procedures were
      performed because of urinary incontinence, upper urinary tract deterioration
      and/or failure of conservative treatment (oxybutynin, clean intermittent
      catheterization--ICC). In 2 patients, reaugmentation was necessary. Urodynamic
      studies were performed on a regular basis, preoperatively and postoperatively.
      Based on their experiences, the authors conclude that recognition of changes in
      bladder capacity and/or compliance and especially the risk of developing upper
      urinary tract changes is only possible by performing urodynamic studies
      regularly. Urodynamics is also essential in decision making processes regarding
      redo surgeries (reaugmentation, transient or permanent urinary diversion).

PMID- 10957868
TI  - [Chronic perchloroethylene poisoning].
AB  - The authors describe the clinical features of the chronic perchloroethylene
      poisoning discussing their own 7 cases (2 women and 5 men). The 2 women worked as
      dry-cleaner, the 5 men performed degreasing of metal objects. The mean age of the
      patients was 46 (36-55), the exposure time 9.1 (0.5-30) years. In 3 cases the
      level of the exposure exceeded the maximum allowable concentration verified by
      the measurement of the perchloroethylene in the air of the workplace. One patient
      suffering from a serious cranial nerve lesion was not informed on the toxic
      exposure, so worked without any protective devices. 3 patients had an isolated
      lesion of the nervous system, 4 one an isolated hepatic damage. The authors draw
      attention to importance of the prevention.

PMID- 10957869
TI  - [Remembering Tibor Nonay, on the occasion of his birthday anniversary].

PMID- 10957870
TI  - [Dr. Zoltan Magyary Gero - hospital director and chief surgeon in Keszthely,
      Hungary].

PMID- 10957871
TI  - [Antibiotics and allergy].

PMID- 10957873
TI  - [Effect of clonidine].

PMID- 10957872
TI  - [Cytokines and cell adhesion molecules in pathologic processes].

PMID- 10957874
TI  - [Heart-lung transplantation and the Marfan syndrome].

PMID- 10957875
TI  - [Dr. Frigyes Verzar and the first insulin therapy in Hungary].

PMID- 10957876
TI  - [Comorbidity of rhinosinusitis and asthma].

PMID- 10957877
TI  - [Spirometric pulmonary age and its correlation with the chronological age of
      asthma patients].
AB  - AIMS: Pulmonary age as a linear regression spirometric index, expresses pulmonary
      ventilatory function. OBJECTIVE: A pilot study was done to assess the differences
      of the values of the pulmonary age index and chronological age in patients with
      bronchial asthma and healthy volunteers. MATERIAL AND METHOD: We studies 111
      subjects, 31 healthy and 80 with asthma. RESULTS: All of them underwent
      spirometry. Healthy individuals showed a mean chronological age of 35 years, and
      a pulmonary age of 26 years. Asthmatic patients showed a mean chronological age
      of 38 years, and a pulmonary age of 59 years. CONCLUSION: Both the time course
      and the severity of the disease increased pulmonary age.

PMID- 10957878
TI  - [A diagnostic instrument for allergic rhinitis].
AB  - AIMS: Allergic rhinitis is the most common chronic disease in the upper
      respiratory tract, requiring better diagnostic methodology to counteract its
      onslaught. MATERIAL AND METHOD: This study included 116 subjects by random
      election, sex indistinct, between 1 and 68 years old with an average of 24.6.
      Data were obtained by medical history, measure levels of circulating eosinophils,
      serum IgE, mucous nasal eosinophils and coproparasitoscopic test. The subjects
      were divided in two groups, 58 patients with allergic rhinitis and 58 health
      subjects. RESULTS: From total subjects, 56.3% were female, 18.9% showed high
      levels of circulating eosinophils and sera IgE. 24.1% had positive identification
      of eosinophils in nasal mocous and 25% suffered parasitosis. In the rhinitis
      group, the average time of evolution was 5.3 years, in 80% with perennial
      presentation, 37.9% showed environmental exposure to allergens at home (p = NS),
      56.8% had family history of allergy, 60% had more than twice monthly acute
      crisis, 29.3% had risen above the upper level of circulating eosinophils (p =
      0.0049), 25.8% had high levels of IgE (p = 0.0002), in 37.93% were found nasal
      mucous eosinophils (p = 0.0009) and in 10.34% were identified intestinal
      parasitosis (p = n.s.). CONCLUSION: In accordance with this work, it is necessary
      to promote a change in attitude, utilizing the medical history as a diagnostic
      instrument and do not restrict prevention and opportunity in treatment to
      laboratory results.

PMID- 10957879
TI  - [Apoptosis in allergic disease].
AB  - Apoptosis (cell programmed death) it is a mechanism that implicate a
      physiological suicide, to keep the cellular homeostasis in big amount of tissues.
      Fas (APO-1; CD95) system is one of the most important cellular responsible via to
      induce apoptosis on different tissues. Eosinophillia on peripheral blood and
      tissues are the main characteristics on allergic like asthma. Eosinophil
      apoptosis is upper regulated in those diseases by IL-5 y GM-CSF. Corticoids,
      teophyllin and some macrolids have been used like apoptosis inductors on
      eosinophills, these could be a novel mechanism to promote a better solution on
      inflammatory allergic diseases.

PMID- 10957881
TI  - The National Nursing Home Survey: 1997 summary.
AB  - OBJECTIVES: This report presents estimates of nursing home facilities, their
      current residents and discharges in the United States. Data are presented on
      facility characteristics, demographic characteristics, utilization measures,
      health and functional status of current residents, and discharges. METHODS: Data
      used in this report are based on data collected from the 1997 National Nursing
      Home Survey. The survey collects information about providers and recipients of
      care from nursing home facilities.

PMID- 10957880
TI  - [Asthma and the environment in the Lagunera district].
AB  - AIMS: The characteristics and real dimension of the environmental problems are
      frequently unknown. These results in a poor knowledge about health impact and
      deficient planning of the measures required for their protection. Asthma is a
      prior health problem at Comarca Lagunera. OBJECTIVE: The analysis of environment
      characteristics that could affect its presentation is the objective of this
      paper. MATERIAL AND METHOD: We took information form several official bureaus and
      regional records. It identified that the coexistence of some factors, like
      regional weather characteristics, with extreme temperature and frequent dust
      storm, growing deforest, dominant flora and acute and chronic contamination by
      particulates material, mainly at urban areas, could explain the epidemiological
      profile of the disease in this urban area so an interdisciplinary participation
      is required for solving this problem. RESULTS: In the Comarca Lagunera, several
      factors coexist which precipitate symptoms in asthmatic subjects: climatological
      features which favor the inflammatory process and increase susceptibility to
      respiratory tract infections which can set off asthmatic crises. CONCLUSION: The
      epidemiological behavior os asthma in this regions may be associated with its
      climatological characteristics.

PMID- 10957882
TI  - Three-dimensional image and virtual dissection program of the brain made of
      Korean cadaver.
AB  - The three-dimensional (3D) structure of the brain needs to be understood for
      accurate diagnosis and treatment of brain diseases. The brain of a cadaver may
      not always be available for dissection when it is needed. To overcome this
      problem, we attempted to create a 3D image and virtual dissection program of the
      brain using a Korean cadaver. The brain extracted from a Korean male cadaver was
      embedded in gelatin solution. 130 MRI of the brain were taken and 130 serially
      sectioned specimens were made. All of MRI and specimens were inputted into the
      computer, and 10 brain components were manually segmented. A 3D image and virtual
      dissection program of the brain was made. Various virtual dissection functions
      were established, such as 1) sectioning the 3D image of the brain at free angles
      to represent its plane as a real image, segmented image, and MRI, 2) identifying
      the brain components represented in the sectioned plane, and 3) rotating the 3D
      image of the whole brain or the selected brain components at free angles. The
      resulting virtual dissection program of the brain is helpful in better
      understanding the 3D location and shape of the brain components and it is
      expected to be used as a CD-title or through Internet as an educational tool for
      medical students and doctors.

PMID- 10957884
TI  - Clinical breast examination for screening of asymptomatic women: the importance
      of clinical breast examination for breast cancer detection.
AB  - Of 489 asymptomatic women who were referred to our institute from other screening
      clinics, 46 were eventually proven to be breast cancer patients, and this number
      equated to 8.1% of the 565 breast cancer patients treated in our institute during
      the period of January 1997 to December 1998. Among the 46 cancer patients of the
      initial 489 asymptomatic women, twenty-five (54.35%) were detected by mammogram
      alone, six (13.04%) by clinical breast examination (CBE) alone, and the remaining
      15 (32.61%) by both mammogram and CBE. In context with age, the mammographic
      sensitivity for cancer detection was 100% for women aged over 60, 91% for 50s,
      78.9% for 40s, and 75% for 30s, and inversely correlated with the patient's age.
      Among the 25 cancers detected by mammogram alone, 18 (72%) belonged to DCIS or
      stage I. In contrast, four (66.7%) of six cancers detected by CBE alone and nine
      (60%) of 15 cancers by both CBE and mammography were included in stage IIa or
      IIb. However, the total incidence of early cancers (stages 0 and I) was
      significantly higher in the screening group than in the symptomatic group (p <
      0.01). These results suggest that the role of mammography is important in the
      detection of cancers in their earlier stage and CBE is helpful in reducing false
      negative results in breast cancer screening. In conclusion, film mammography is
      the best tool for the detection of microcalcification and is useful for the
      detection of earlier lesions, but is not perfect for the detection of breast
      cancer particularly in young women. A careful CBE is an essential part of breast
      screening in order to reduce false-negative results.

PMID- 10957883
TI  - Reconstructive surgery in primary malignant and aggressive benign bone tumor of
      the proximal humerus.
AB  - Primary malignant bone tumors of the proximal humerus have traditionally been
      treated by forequarter amputation. However, with the increased interest in limb
      salvage operations, efforts have been made to improve reconstructive surgery and
      some methods have become available for tumor control and preservation of a useful
      distal limb. This report describes three reconstructive techniques used for
      reconstruction of the humerus following primary tumor excision. We followed 11
      patients treated by reconstructive surgery following tumor excision for primary
      malignant and aggressive benign bone tumors in the proximal humerus. The average
      follow-up period was 35.6 months. The histologic diagnosis included osteosarcoma
      (9), chondrosarcoma (1) and giant cell tumor (1). The options for reconstructive
      surgery following tumor excision were six prosthetic arthroplasties with low heat
      treated autobone, four arthroplasties with Ender nail and bone cement, and one
      arthroplasty with custom-made tumor prosthesis. We performed a retrospective
      analysis regarding functional status, as well as local recurrence, distant
      metastasis and complication. The functional status at final follow-up averaged 16
      points (53.3%) overall: 17 points (56.7%) in the six prosthetic arthroplasties
      with low heat treated autobone; 15 points (50.0%) in two of four arthroplasties
      with Ender nail and bone cement (the two others died); and 16 points (53.3%) in
      the one arthroplasty with custom-made tumor prosthesis. Local recurrence was not
      observed in any of the cases. The complications noted were one nonunion between
      reimplanted, low heat treated autobone and the normal distal humerus and two
      metal failures. Each of these techniques for reconstructive surgery resulted in a
      relatively good outcome, although somewhat better results were found in the case
      of prosthetic arthroplasty with low heat treated autobone.

PMID- 10957885
TI  - Serologic and histopathologic study of Chlamydia pneumoniae infection in
      atherosclerosis: a possible pathogenetic mechanism of atherosclerosis induced by
      Chlamydia pneumoniae.
AB  - Chronic infection and inflammation have recently been implicated as important
      etiologic agents for atherosclerosis in general and, in particular, ischemic
      heart disease. Several agents have been suggested as possible candidates for the
      chronic inflammation including cytomegalovirus, Helicobacter pylori and Chlamydia
      pneumoniae. We hypothesized that a vascular infection with C. pneumoniae may
      induce a chronic inflammatory reaction in the host vascular tissue and activated
      inflammatory cells may express inflammatory mediators such as cyclooxygenase-2
      (COX-2) and matrix metalloproteinases (MMPs). At first, we evaluated the
      relationship between C. pneumoniae infection and atherosclerosis indirectly by
      serologic study, and then, to confirm our hypothesis, we performed an
      immunohistochemical study of atherosclerotic plaques. The seropositive rate of
      anti-Chlamydia pneumoniae IgG was higher in the disease group (Group I, 59.8%, n
      = 254) than in the negative control group (Group III, 47.4%, n = 97) (p = 0.041),
      but the anti-Chlamydia pneumoniae IgA was not different in seropositivity between
      the two groups (Group I, 64.6%; Group III, 57.7%). The simultaneous seropositive
      rates of both IgG and IgA were 56.7% in Group I and 43.3% in Group III (p =
      0.033). In subgroups without the conventional risk factors of atherosclerosis,
      these findings were more prominent. Furthermore, we performed immunohistochemical
      staining on the atherosclerotic aortic tissues obtained from patients that were
      seropositive to C. pneumoniae (n = 5), by using antibodies to C. pneumoniae, COX
      2, and MMP-9. The immunoreactivity for COX-2 and MMP-9 increased in the
      atherosclerotic plaques itself, predominantly in the surrounding area of
      immunoreactive C. pneumoniae. These findings support our hypothesis and C.
      pneumoniae may participate in a pathogenetic mechanism for atherogenesis or
      progression of atherosclerosis. The present study may open a promising
      perspective concerning future therapeutic trials of chronic inflammation related
      atherogenesis under pathophysiological conditions.

PMID- 10957887
TI  - A quantitative evaluation of pigmented skin lesions using the L*a*b* color
      coordinates.
AB  - The evaluation of pigmentary skin lesions by clinical doctors has been based on
      subjective and qualitative judgements. Observations have mostly relied on visual
      inspection, making the effects of treatment difficult to evaluate with any
      precision. For this reason there is a real need for an objective method to
      evaluate prognosis after treatment. Recent scientific measurements such as
      reflectance spectrophotometry and reflectance colorimetry have provided accurate
      quantitative color information about skin lesions, but these techniques are
      costly and difficult to apply in the clinical field. The purpose of this study
      was to develop a simple and cost-effective way of evaluating treatment results.
      We have developed a software program using the L*a*b* color coordinate system to
      quantify the effect of treatment and have successfully demonstrated its clinical
      usefulness. Our method compares the relative color difference between normal skin
      and skin lesions before and after treatment, instead of measuring the absolute
      color of skin lesions. The accuracy of our quantitative color analysis was
      confirmed by the simulated images of hemangioma and ota nevus. Clinical efficacy
      was also confirmed through a blind test involving 3 clinicians who were asked to
      grade the treatment effects of 13 cases of hemangioma and 7 cases of ota nevus.
      These subjective clinical grades correlated well with the treatment results
      obtained using the proposed color analysis system (Correlation coefficient =
      0.84).

PMID- 10957886
TI  - Serum immunoreactivity to S-100 in children with cerebral palsy and delayed
      development and in their healthy parents.
AB  - The passive immunization of pregnant female rats to S-100 protein often leads to
      ultra-structural abnormalities in the brain glial structures of the offspring of
      these rats and induces signs of delayed development in the fetal brain.
      Additionally passive immunization of pregnant animals with certain antigens
      induces permanent Ag-specific changes in the immune response of their offspring.
      The purpose of this study was to investigate serum immunoreactiviy (SIR) to S-100
      in cerebral-palsied and developmentally-delayed children as well as in their
      healthy parents and to evaluate its significance related to radiologic findings
      of brain MRI and single photon emission computed tomography (SPECT). The subjects
      were children with cerebral palsy and delayed development that had abnormal
      findings on brain MRI or Brain SPECT. SIR to S-100 protein was measured by ELISA
      method in the patients, their healthy parents, 20 normal adult controls and 22
      normally developed children. The SIR to S-100 protein was significantly higher in
      the cerebral-palsied and developmentally-delayed children when compared to that
      of the normal control group children. Increased SIRs were detected in healthy
      mothers but not in their fathers. There was no difference of SIR between the
      cerebral-palsied and developmentally-delayed children or any significant
      difference of SIRs according to the findings of the brain MRI or to developmental
      quotients. But, the SIRs to S-100 protein were higher in the group of more
      abnormal findings on brain SPECT.

PMID- 10957888
TI  - A comparative efficacy and safety study of clarithromycin, roxithromycin and
      erythromycin stearate in mild pneumonia.
AB  - The efficacy and safety of clarithromycin, roxithromycin and erythromycin
      stearate in mild pneumonia were compared in an open randomized trial. Eighty-six
      male patients, doing their obligatory military service, ranging between 19 and 24
      years of age (mean 20), were randomly treated: 29 with clarithromycin 500 mg 12
      hourly, 30 with roxithromycin 150 mg 12-hourly, and 27 with erythromycin stearate
      500 mg 6-hourly, each course being administered for 10 days. Seventy-eight
      patients were able to be evaluated for efficacy, 28 receiving clarithromycin, 28
      roxithromycin, and 22 erythromycin stearate. There were no significant
      differences among the groups in terms of clinical success rates (clinical cure or
      improvement: 89% for clarithromycin, 82% for roxithromycin, and 73% for
      erythromycin stearate, p = 0.32). However, we found that there were significant
      differences among the groups in terms of clinical cure rates (75% for
      clarithromycin, 64% for roxithromycin, and 41% for erythromycin stearate, p =
      0.04). Adverse events, mostly gastrointestinal, caused discontinuation of
      treatment in 3.4% of the patients in the clarithromycin group, in 6.6% of the
      patients in the roxithromycin group, and in 18.5% of the patients in the
      erythromycin stearate group. The results indicate that there were no
      statistically significant differences among the three treatment groups in terms
      of clinical success rates, but that clarithromycin and roxithromycin were better
      tolerated.

PMID- 10957889
TI  - Expression of cyclins in ductal hyperplasia, atypical ductal hyperplasia and
      ductal carcinoma in situ of the breast.
AB  - Cyclin/cdc complexes are known to function in cell-cycle regulation. Cyclin
      D1/cdk4 and -6 complexes, which functions as a G1-S checkpoint and cyclin B1/cdc2
      complexes, a G2-M checkpoint are essential for DNA synthesis and mitosis,
      respectively. Thus, dysregulated overexpression of cyclins appears to be involved
      in uncontrollable cell proliferation and early tumor development. We investigated
      the expression and proliferative index of cyclin D1 (PIcyclin D1), cyclin B1
      (PIcyclin B1) and Ki-67 (PIKi-67) using immunohistochemical staining on 15 cases
      of ductal hyperplasia (DH), 26 cases of atypical ductal hyperplasia (ADH) and 43
      cases of ductal carcinoma in situ (DCIS) of the breast in order to evaluate
      whether these cyclins are associated with abnormal cell proliferation and play a
      role in tumor development from ADH to carcinoma. Furthermore, we investigated
      whether the expression and proliferative index of the cyclins and Ki-67 are
      correlated with the histologic grade according to the Van Nuys classification and
      with the histologic subtype according to traditional classification. Finally, we
      estimated the correlation coefficient among PIcyclin D1, PIcyclin B1, PIKi-67 and
      estrogen receptor in ADH and DCIS. The expression of cyclin D1 was detected in
      39.5% of DCIS and 7.7% of ADH cases. In the DH cases, expression of cyclin D1 was
      not found. Expression of cyclin B1 was also detected in 69.7% of DCIS, 50.0% of
      ADH and 93.3% of the DH cases. The PIcyclin D1 was significantly different among
      these three groups. Moreover, the PIcyclin D1 and PIKi-67 were differed
      significantly between the low grade DCIS and ADH cases. However, PIcyclin B1 only
      appeared to be significantly different between the total DCIS and ADH. Results of
      the correlation coefficient among PIcyclin D1, PIcyclin B1 and PIKi-67 were
      positively correlated with each other. No significant correlation was found
      between the expression of ER and cyclin D1 in ADH and DCIS. In summary, our
      results support the hypothesis that a cyclin D1 and cyclin B1 protein aberration,
      along with Ki-67, may act as a relatively early event in the tumor development
      from ADH to carcinoma.

PMID- 10957890
TI  - Role of different peripheral components in the expression of neuropathic pain
      syndrome.
AB  - Peripheral nerve injury frequently leads to neuropathic pain like hyperalgesia,
      spontaneous pain, mechanical allodynia, thermal allodynia. It is uncertain where
      the neuropathic pain originates and how it is transmitted to the central nervous
      system. This study was performed in order to determine which peripheral component
      may lead to the symptoms of neuropathic pain. Under halothane anesthesia, male
      Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and
      cutting the tibial and sural nerves and leaving the common peroneal nerve intact.
      Behavioral tests for mechanical allodynia, thermal allodynia, and spontaneous
      pain were performed for 2 weeks postoperatively. Subsequently, second operation
      was performed as follows: in experiment 1, the neuroma was removed; in experiment
      2, the dorsal roots of the L4-L6 spinal segments were cut; in experiment 3, the
      dorsal roots of the L2-L6 spinal segments were cut. Behavioral tests were
      performed for 4 weeks after the second operation. Following the removal of the
      neuroma, neuropathic pain remained in experiment 1. After the cutting of the L4
      L6 or L2-L6 dorsal roots, neuropathic pain was reduced in experiments 2 and 3.
      The most remarkable relief was seen after the cutting of the L2-L6 dorsal roots
      in experiment 3. According to the fact that the sciatic nerve is composed of the
      L4-L6 spinal nerves and the femoral nerve is composed of the L2-L4 spinal nerves,
      neuropathic pain is transmitted to the central nervous system via not only the
      injured nerves but also adjacent intact nerves. These results also suggest that
      the dorsal root ganglion is very important in the development of neuropathic pain
      syndrome.

PMID- 10957891
TI  - Issues and problems of adaptation of North Korean defectors to South Korean
      society: an in-depth interview study with 32 defectors.
AB  - The number of North Koreans defecting to South Korea is increasing rapidly. They
      are important people to South Korean society not only for humanitarian reasons,
      but also for their impact on the future Korean unification and the integration of
      the two different South and North Korean peoples. However, the defectors have
      experienced many difficulties in their adaptation to South Korean society due to
      their own characteristics and due to the misunderstandings of the South Korean
      people. To obtain comprehensive qualitative data about the characteristics and
      difficulties of North Korean defectors' adaptation to South Korean society, 58
      semi-structured in-depth interviews were performed with 32 defectors who had
      entered South Korea from 1990 to 1997. Four categories of adaptation difficulties
      were encountered, which are related with the defectors' suspiciousness, different
      ways of thinking, searching for new sets of values, and with the prejudice of the
      South Korean people. Finally, three areas of suggestions for the more successful
      adaptation of the defectors to South Korean society were made; a need for more
      comprehensive perspectives on the defectors' adaptation, suggestions regarding
      educational programs and suggestions for educating the South Korean people.

PMID- 10957892
TI  - Sulfhydryl modification affects coronary artery tension by changing activity of
      delayed rectifier K+ current.
AB  - It has been reported that a change in the cellular redox state may be involved in
      the regulation of vascular tone, but the underlying mechanism is not fully
      understood. The present study was designed to investigate the cellular effect of
      sulfhydryl modifying agents in the coronary artery of rabbit using the tension
      measurement and whole cell clamping method. The application of diamide, a
      sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in
      a dose dependent manner. The fact that this diamide-induced relaxation was
      significantly attenuated by a pretreatment of 4-AP, and the coronary arteries
      precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4
      AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries.
      Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was
      significantly enhanced by the membrane permeant oxidizing agents, diamide and
      DTDP, and were reversed by subsequent exposure to the reducing agent, DTT.
      Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had
      any effect on the activity of IdK, indicating that intracellular sulfhydryl
      modification is critical for modulating IdK activity. The Diamide failed to
      significantly alter the voltage dependence of the activation and inactivation
      parameters, and did not change the inactivation process, suggesting that diamide
      increases the number of functional channels without altering their gating
      properties. Since IdK has been believed to play an important role in regulating
      membrane potential and arterial tone, our results about the effect of sulfhydryl
      modifying agents on coronary arterial tone and IdK activity should help
      understand the pathophysiology of the diseases, where oxidative damage has been
      implicated.

PMID- 10957893
TI  - Emerging antimicrobial resistance, plasmid profile and pulsed-field gel
      electrophoresis pattern of the endonuclease-digested genomic DNA of Neisseria
      gonorrhoeae.
AB  - Resistant gonococci are very prevalent in many countries, particularly in Asia.
      This study was conducted to determine the trend of resistance, the effect of
      decreasing the ciprofloxacin susceptibilities of gonococci on the prevalence of
      penicillinase-producing N. gonorrhoeae (PPNG), and to compare the epidemiology of
      strains with the previous studies. A total of 602 strains of gonococci were
      isolated from prostitutes in 1997-1999. Antimicrobial susceptibility was tested
      by NCCLS disk diffusion and agar dilution methods. For epidemiologic analysis,
      plasmid analysis and pulsed-field gel electrophoresis (PFGE) were performed. The
      proportion of PPNG remained high (79%), and the strains with decreased
      susceptibility to ciprofloxacin increased significantly from 67% in 1997 to 84%
      in 1999. Compared to our previous study, the PFGE patterns were similar, while
      the proportion of strain with the 3.2-MDa plasmid markedly decreased. In
      conclusion, a rapid increase in ciprofloxacin-nonsusceptible strains may suggest
      difficulties in the treatment of gonococcal infections in the near future with
      the drug. The recent decrease of PPNG with the 3.2-MDa plasmid may suggest that
      there is an epidemiological change in gonococcal infections, and the prevalence
      of related PFGE patterns suggests the dissemination of a few clones among the
      high risk populations.

PMID- 10957894
TI  - Serum ferritin in healthy subjects and type 2 diabetic patients.
AB  - In order to study the relationship between the serum ferritin level and the
      components of the insulin resistance syndrome in type 2 diabetic patients, we
      evaluated fifty type 2 diabetic patients who were selected according to NDDG/WHO
      criteria from those patients attending Korea University Hospital from 1997 to
      1998. Twenty-five healthy non-diabetic subjects of comparable age and sex
      distribution acted as a control group. The results showed that the value of log
      ferritin was higher in the type 2 diabetes patients than the control subjects,
      but not at a statistically significant level (p = 0.09). Log ferritin was
      correlated with fasting blood sugar level (r = 0.235, p = 0.048) and body mass
      index (BMI) (r = 0.285, p = 0.05). In the type 2 diabetic patients, log ferritin
      was correlated with fasting C-peptide (r = 0.478, p = 0.009). In the control
      subjects, log ferritin was correlated only with BMI (r = 0.477, p = 0.012). In a
      stepwise multiple regression analysis, the diabetic group showed a significant
      correlation between fasting C-peptide and log ferritin (p = 0.001). In the
      control group, the fasting sugar level was significantly correlated with log
      ferritin (p = 0.034). These results suggest that serum ferritin can be employed
      as a marker of not only glucose homeostasis but also insulin resistance both in
      type 2 diabetic and control subjects.

PMID- 10957895
TI  - The usefulness of minimal F-wave latency and sural/radial amplitude ratio in
      diabetic polyneuropathy.
AB  - The possibility of whether minimal F-wave latency and a simple ratio between the
      sural and superficial radial sensory response amplitudes may provide a useful
      electrodiagnostic test in diabetic patients was investigated in this report. To
      evaluate the diagnostic sensitivity of minimal F-wave latency, the Z-scores of
      the minimal F-wave latency, motor nerve conduction velocity (MCV), amplitude of
      compound muscle action potentials (CMAP), and distal latency (DL) of the median,
      ulnar, tibial, and peroneal nerve were compared in 37 diabetic patients. For the
      median, ulnar, and tibial nerves, the Z scores of the minimal F-wave latency were
      significantly larger than those of the MCV. In addition for all four motor
      nerves, the Z scores of the minimal F-wave latency were significantly larger than
      those for the CMAP amplitude. Furthermore, 19 subjects showing abnormal results
      in the standard sensory nerve conduction study had a significantly lower
      sural/radial amplitude ratio (SRAR), and 84% of them had an SRAR of less than
      0.5. In conclusion, minimal F-wave latency and the ratio between the amplitudes
      of the sural and superficial radial sensory nerve action potential are sensitive
      measures for the detection of nerve pathology and should be considered in
      electrophysiologic studies of diabetic polyneuropathy.

PMID- 10957896
TI  - Assignments of the tyrosinase related protein-1 and -2 genes to human chromosome
      bands 9p23 and 13q32.1 by in situ hybridization.
AB  - To determine the precise chromosomal localization of tyrosine related protein-1
      and -2 (TRP-1 and TRP-2) genes by fluorescence in situ hybridization, we used
      DNAs isolated from human bacterial artificial chromosome clones. They contain
      genomic sequences with approximately 120 kb inserts for TRP-1 and TRP-2. The TRP
      1 and TRP-2 genes were assigned to human chromosome bands 9p23 and 13q32.1,
      respectively. These results confirmed the previously mapped location for the TRP
      1 gene and more precisely located the TRP-2 gene, which had previously been
      mapped to chromosome 13q31-q32.

PMID- 10957897
TI  - Inflammatory pseudotumor of the urinary bladder in a child.
AB  - The inflammatory pseudotumor of the urinary bladder is rare, especially in
      children. It is a benign proliferative lesion of the submucosal stroma easily
      mistaken for a sarcoma clinically, so it should be differentiated from a
      malignant neoplasm. We report the case of bladder inflammatory pseudotumor in a 7
      year-old girl.

PMID- 10957898
TI  - Ocular deviation after unilateral laser in situ keratomileusis.
AB  - Laser keratomileusis and excimer laser photorefractive keratectomy in situ are
      widely used therapies for treating myopia. The corrections of refractive error by
      glasses or contact lens result in a relatively equal refractive correction on
      both eyes. However, refractive surgery on a single eye can cause a focus
      disparity between both eyes and may result in the impairment of fusion leading to
      strabismus. This article aims to report a case where diplopia and esotropia
      occurred 1 month after laser keratomileusis (LASIK) in situ for the correction of
      myopia.

PMID- 10957899
TI  - A case of membranoproliferative glomerulonephritis associated with a hydatidiform
      mole.
AB  - We treated a 54-year-old woman who was suffering from membranoproliferative
      glomerulonephritis associated with a complete type of hydatidiform mole. The
      renal manifestations were proteinuria and hematuria. A renal biopsy, performed
      before gynecologic management, disclosed focal and segmental subendothelial
      deposits with a proliferation of the mesangial cell and showed irregularly
      thickened capillary loops by light and electronmicroscoy. Genralized edema,
      proteinuria and hematuria were completely recovered by suction and curettage of
      the hydatidiform mole with prophylactic chemotherapy. The clinical manifestation
      of earlier presented 3 cases have been the nephrotic syndrome. The common feature
      of them was a complete remission of the nephropathy after the removal of the
      hydatidiform mole. The relationship between the hydatidiform mole and
      glomerulonephritis remains unresolved at present. But we concluded that the
      hydatidiform mole might be a cause of glomerulonephritis in this case.

PMID- 10957900
TI  - Epidermolysis bullosa simplex (Dowling-Meara type) associated with pyloric
      atresia and congenital urologic abnormalities.
AB  - We report a case of epidermolysis bullosa simplex, Dowling-Meara type (EBS-DM),
      which was associated with congenital pyloric atresia (PA) and various urologic
      abnormalities, a diagnosis confirmed by immunofluorescence mapping and electron
      microscopic findings. Immunofluorescent mapping showed the serum from a patient
      with bullous pemphigoid faintly binding to the floor of the blister, and
      monoclonal antibodies against type IV and VII collagens were also stained on the
      floor of the blister. Electron microscopy showed epidermolytic cleavage and
      prominent clumping of tonofilaments in the basal and suprabasal keratinocytes. An
      abdominal radiograph and barium swallow showed a complete obstruction at the
      pyloric channel level. The widespread bullae healed without any scar formation
      and the bullae formation was localized on the extremities after 3 months of age
      without any specific treatment. Multiple urologic abnormalities such as bilateral
      hydronephrosis, hydroureter and a distended bladder with trabeculation were
      observed at 12 months of age. Currently, with the patient at 4 years of age,
      bullae still appear on the hands and feet and nail shedding can be observed. The
      patient's father, a paternal uncle and a paternal aunt had had similar bullous
      eruptions in infancy, all of which had improved spontaneously by the age of one.

PMID- 10957901
TI  - Amanita virosa induced toxic hepatitis: report of three cases.
AB  - We report here three cases of Amanita virosa induced toxic hepatitis. Two of the
      three cases recovered but the other died 10 days after mushroom ingestion. Since
      the mortality of Amanita mushroom induced toxic hepatitis is very high, prompt
      diagnosis and aggressive therapeutic measures should be initiated as soon as
      possible. Our cases showed that the initial serum aminotransferase levels might
      not predict the clinical outcome of the patient, but that the prothrombin time
      (PT) seemed to be a more useful prognostic marker. Close monitoring of
      aminotransferase levels and PT as well as appropriate therapy are recommended.
      All three cases showed signs of proteinuria and we were able to characterize
      mixed tubular and glomerular type proteinuria at 3 or 4 days after ingestion in
      two cases. Among the previously reported Korean cases of suspected Amanita
      induced toxic hepatitis, most species could not be identified except for four
      cases of Amanita virosa. No cases of Amanita phalloides induced toxic hepatitis
      have been identified in Korea so far.

PMID- 10957902
TI  - A case of endobronchial aspergilloma.
AB  - Pulmonary aspergillosis may be classified under three categories, depending upon
      whether the host is atopic or immunocompromised: invasive aspergillosis, allergic
      bronchopulmonary aspergillosis (ABPA) or aspergilloma. However, it is not always
      possible to effectively categorize this disease. We experienced a case of
      endobronchial aspergilloma, which was difficult to categorize, in a healthy male
      patient. The chest X-ray and computed tomography showed an ill-defined nodule
      mimicking lung cancer. Fiberoptic bronchoscopy revealed an aspergilloma without
      cavity formation in the left lower laterobasal segmental bronchial orifice. The
      aspergilloma was removed and the patient's symptoms were relieved. We present
      this unusual case with a review of the literature.

PMID- 10957903
TI  - Islet cell hyperplasia of the pancreas presenting as hyperinsulinemic
      hypoglycemia in an adult.
AB  - A 72-year-old man who had suffered several episodes of syncope was diagnosed as
      having hyperinsulinemic hypoglycemia. Although imaging studies and percutaneous
      transhepatic portal venous sampling did not reveal the existence of any tumors in
      the pancreas, distal pancreatectomy was performed because the possibility of a
      small pancreatic endocrine tumor could not be completely rejected. External
      examination of the surgically removed pancreas did not reveal any tumors.
      Microscopically, the pancreas exhibited diffuse islet cell hyperplasia without
      nesidioblastosis. The patient remains euglycemic and has tolerated 24-hour
      fasting without any medication for a period of 10 months after the operation.

PMID- 10957904
TI  - Management of peripheral arterial disease (PAD). TransAtlantic Inter-Society
      Consensus (TASC).

PMID- 10957905
TI  - Management of peripheral arterial disease (PAD). TransAtlantic Inter-Society
      Consensus (TASC). Section B: intermittent claudication.

PMID- 10957906
TI  - Management of peripheral arterial disease (PAD). TransAtlantic Inter-Society
      Consensus (TASC). Section C: acute limb ischaemia.

PMID- 10957907
TI  - Management of peripheral arterial disease (PAD). TransAtlantic Inter-Society
      Consensus (TASC). Section D: chronic critical limb ischaemia.

PMID- 10957908
TI  - Bone marrow transplantation in the private sector.

PMID- 10957909
TI  - Reducing mother-to-child transmission of HIV.

PMID- 10957910
TI  - Amniocentesis--too dangerous and too late?

PMID- 10957911
TI  - Anaesthesia in rural hospitals.

PMID- 10957912
TI  - Serious consequences to misuse of propofol anaesthetic.

PMID- 10957913
TI  - Flood disease control--moving smartly to save lives.

PMID- 10957914
TI  - Hanging in there for a new TB drug.

PMID- 10957915
TI  - Post-exposure prophylaxis for HIV.

PMID- 10957916
TI  - Radiosurgery in South Africa.

PMID- 10957918
TI  - Saving mothers in South Africa.

PMID- 10957917
TI  - A patient requiring 1,000 units of insulin per day!

PMID- 10957919
TI  - A neonatal death associated with rotavirus infection--detection of rotavirus
      dsRNA in the cerebrospinal fluid.

PMID- 10957920
TI  - Malaria at the Chris Hani Baragwanath Hospital, Soweto.

PMID- 10957921
TI  - A review of maternal deaths in South Africa during 1998. National Committee on
      Confidential Enquiries into Maternal Deaths.
AB  - OBJECTIVE: To document the prevalence and causes of maternal mortality and to
      identify avoidable factors, missed opportunities and substandard care related to
      these deaths. METHOD: Maternal deaths are notifiable; when a maternal death
      occurs a maternal death notification form is filled in and sent to the provincial
      Maternal, Child and Women's Health (MCWH) units. Provincial assessors assess the
      death and submit a report. This report is forwarded to the National Committee on
      Confidential Enquiries into Maternal Deaths (NCCEMD), where the data are collated
      and the prevalence, pattern of disease, avoidable factors, missed opportunities
      and substandard care pertaining to maternal deaths are described. RESULTS: Data
      were collected on the maternal deaths occurring during 1998 in South Africa.
      Collection of data on maternal deaths was incomplete and a maternal mortality
      ratio could not be calculated. However, a clear pattern of disease and problems
      in patient care emerged. The 'big five' causes of death were complications of
      hypertensive conditions in pregnancy, AIDS, obstetric haemorrhage, pregnancy
      related sepsis and pre-existing medical conditions. Women aged 30 years and older
      were at greater risk of dying than younger women. Women in their first pregnancy
      or who had had 5 or more pregnancies were also at greater risk. Obstetric
      haemorrhage was the most common cause of death at level 1 hospitals, AIDS at
      level 2 hospitals and hypertensive diseases at level 3 hospitals. The vast
      majority of anaesthetic-related deaths occurred at level 1 hospitals. Non
      attendance and delayed attendance at the health institutions were the most common
      patient-orientated problems. Poor transport facilities and lack of intensive care
      facilities were the major administrative problems. Problems in the care of women
      occurred in more than half the cases of maternal death, the majority at the
      primary level of care. Poor initial assessment and diagnosis of cases, especially
      at secondary level of care, failure to follow standard protocols at primary and
      secondary levels, and poor monitoring of patients at all levels of care were the
      common health worker-related problems. CONCLUSION: Ten key recommendations based
      on this information have been made by the NCCEMD; if implemented these will
      result in a reduction of maternal deaths.

PMID- 10957922
TI  - Lipoprotein(a) determination and risk of cardiovascular disease in South African
      patients with familial hypercholesterolaemia.
AB  - OBJECTIVE: A raised plasma level of lipoprotein(a) (Lp(a)) is an established
      genetic risk factor for coronary heart disease (CHD), particularly in patients
      with concomitant elevation of low-density lipoprotein (LDL) cholesterol. The
      current study focused on the comparison of two commercially available Lp(a) assay
      kits to determine whether differences observed in measured Lp(a) levels could be
      deemed negligible in CHD risk assessment in familial hypercholesterolaemic (FH)
      patients. DESIGN: To compare results obtained on duplicate plasma samples using
      two commercially available Lp(a) measuring kits, the immunoradiometric assay
      (RIA) and the enzyme-linked immunoabsorbent assay (ELISA). SETTING: Division of
      Human Genetics, Department of Obstetrics and Gynaecology, University of
      Stellenbosch, Tygerberg, South Africa and the Institute for Medical Biology and
      Human Genetics, University of Innsbruck, Austria. SUBJECTS: Plasma samples were
      obtained from 146 family members of 65 molecularly characterised South African FH
      families for comparative analysis. RESULTS: Using the RIA method, 34 samples
      (23%) considered to be in the normal range by the ELISA technique, were placed in
      the high-risk group (> 30 mg/dl). Only one sample, considered to have a normal
      Lp(a) level with the RIA method, was categorised by the ELISA technique as high
      risk. CONCLUSION: Our data demonstrate that measurements of Lp(a) using the RIA
      method (the only assay available in South Africa at the time of this study)
      differ significantly from those obtained by the reference ELISA technique,
      suggesting that misclassification could lead to inaccurate CHD risk assessment.
      This is an important consideration in Afrikaner FH families, where plasma levels
      of Lp(a) have been shown to be elevated significantly in FH patients compared
      with non-FH individuals.

PMID- 10957923
TI  - To what extent does South African mental health and substance abuse research
      address priority issues?
AB  - OBJECTIVE: To investigate the extent to which South African mental health
      research addresses priority issues. DESIGN: Cross-sectional survey of conference
      presentations. SETTING: The most recent conferences of the following professional
      societies: the Epidemiological Society of Southern Africa, the Psychological
      Society of South Africa, the Society of Psychiatrists of South Africa, and the
      South African Association for Child and Adolescent Psychiatry and Allied
      Disciplines. MAIN OUTCOME MEASURES: Whether the presentations addressed priority
      areas as defined in the list 'Selected priority areas of research' compiled by
      the Mental Health and Substance Abuse Thrust of the Medical Research Council, and
      if so which priority areas were addressed. RESULTS: There were 627 presentations,
      with 267 (43%) on mental health or substance abuse. Seventy-eight papers (29%)
      reported original research in a priority area identified by the Medical Research
      Council. Of these, 73 (94%) were on mental health and 5 (6%) were on substance
      abuse. Of the 73 papers on mental health, 33 (45%) addressed topics in health
      problem research, 7 (10%) aetiology research, 22 (30%) intervention research, and
      11 (15%) operational and health systems research. CONCLUSION: Much South African
      mental health research does not address priority issues. There is a particular
      dearth of research addressing substance abuse research priorities. Funding
      mechanisms and research capacity development initiatives could help to rectify
      the situation.

PMID- 10957924
TI  - Drug-resistant pulmonary tuberculosis in a cohort of southern African goldminers
      with a high prevalence of HIV infection.
AB  - OBJECTIVES: To determine rates of drug resistance to Mycobacterium tuberculosis
      and associated risk factors, including HIV infection. DESIGN: Prospective cohort
      study of patients with pulmonary tuberculosis. SETTING: The study population
      comprised 28,522 men working on four goldmines in Westonaria, Gauteng. Health
      care is provided at a 240-bed mine hospital, Gold Fields West Hospital, and its
      primary health care facilities. SUBJECTS: All 425 patients with culture-positive
      pulmonary tuberculosis identified in 1995. OUTCOME MEASURES: Tuberculosis drug
      resistance on enrollment and after 6 months' treatment. RESULTS: There were 292
      cases of new tuberculosis, 77 of recurrent disease and 56 prevalent cases in
      treatment failure. Two hundred and seven patients (48.7%) were HIV infected.
      Primary resistance to one or more drugs (9%) was similar to the 11% found in a
      previous study done on goldminers in 1989. Primary multidrug resistance (0.3%)
      was also similar (0.8%). Acquired multidrug resistance was 18.1%: 6.5% for
      recurrent disease and 33.9% in treatment failure cases. Neither HIV infection nor
      the degree of immunosuppression as assessed by CD4+ lymphocyte counts was
      associated with drug resistance at the start or end of treatment. New patterns of
      drug resistance were present in 9 of 52 patients in treatment failure at 6
      months, 1 of whom was HIV-infected. CONCLUSION: Primary and acquired drug
      resistance rates are stable in this population and are not affected by the high
      prevalence of HIV infection.

PMID- 10957925
TI  - The evaluation of primary hyperaldosteronism.

PMID- 10957926
TI  - The aldosterone/renin ratio as a screening test for primary aldosteronism.
AB  - OBJECTIVE: To investigate the utility of random outpatient plasma aldosterone and
      renin measurements in screening for primary aldosteronism (PA) in hypertensive
      patients. DESIGN: Clinical records of hypertensive patients who had aldosterone
      and renin determinations over a 3-year period were analysed retrospectively. The
      patients were arbitrarily classified into five groups defined according to the
      aldosterone level and the aldosterone/renin (A/R) ratio: PA (plasma aldosterone >
      500, A/R ratio > or = 1,000; essential hypertension (EHT) (aldosterone < 1,000,
      A/R < 1000); secondary hyperaldosteronism (SHA) (aldosterone > or = 1,000, A/R <
      400); low-renin hypertension (LRHT) (aldosterone < 500, A/R > or = 1,000);
      miscellaneous hyperaldosteronism (MHA) (aldosterone > or = 1,000, A/R 400-1000).
      SETTING: A hypertension clinic in a large teaching hospital. PATIENTS AND
      RESULTS: The sample of 216 hypertensives were classified as follows: EHT 51%,
      LRHT 8%, PA 32%, SHA 7%, and MHA 3%. Mean plasma potassium values were
      significantly lower (P < 0.0001) in the PA group compared with essential
      hypertensives, but plasma K+ was of little utility in identifying individual
      patients with PA, as 71% were normokalaemic. Adrenal computed tomography scans
      were performed on 38 of 69 patients with PA, and revealed definite unilateral or
      bilateral adrenal masses in 7 and probable unilateral masses in a further 4. Five
      patients underwent unilateral adrenalectomy, confirming adrenal adenomas in 4 and
      nodular hyperplasia in 1. The minimum prevalence of PA due to adrenal adenoma or
      hyperplasia was 3.3% of all hypertensives and 10.1% of patients with biochemical
      PA defined by A/R ratio. Patients with biochemical PA had more target organ
      damage, and in general responded more favourably to regimens with spironolactone
      than to conventional therapy. CONCLUSIONS: A random outpatient aldosterone and
      renin measurement identifies a group of hypertensives with biochemical PA in
      which there is a significant prevalence of adrenal adenomas, increased prevalence
      of target organ damage and a good response to spironolactone. These results have
      major implications for the investigation and management of patients with severe
      or resistant hypertension.

PMID- 10957927
TI  - Acid suppression therapy in Barrett's esophagus: the importance of pH monitoring.

PMID- 10957928
TI  - An overview of the upper esophageal sphincter.
AB  - The anatomy and physiology of the upper esophageal sphincter (UES) are complex.
      Much progress has been made over the past few years in our understanding this
      important sphincter. The closing muscles of the UES include the inferior
      pharyngeal sphincter, the cricopharyngeus (CP), and the cervical esophagus. The
      CP is composed of two parts, which may have different functions. The CP is
      innervated by the pharyngeal plexus and the recurrent laryngeal nerve. Tone of
      the UES is probably generated by numerous reflexes rather than by specific tone
      generating circuitry. The major tone-generating muscle is the CP, which is highly
      elastic and produces more active tension the more it is stretched. The UES opens
      by relaxation of the closing muscles, traction by muscles attached to the hyoid
      bone and thyroid cartilage, and pulsion of the bolus. The various muscles of the
      UES behave differently during its many dynamic states, so that similar functions
      are accomplished by different muscles.

PMID- 10957929
TI  - Diagnosis and management of cricopharyngeal achalasia and other upper esophageal
      sphincter opening disorders.
AB  - Recent literature on disorders of the upper esophageal sphincter is reviewed,
      including discussion of advances in measurement, diagnosis, treatment, and
      management. The etiology of upper esophageal sphincter disorders is summarized,
      along with its pathophysiology, with reference to gastroesophageal reflux
      disease. Medical and surgical options for improving pharyngeal clearance and
      minimizing aspiration are also discussed, as is the use of percutaneous
      esophageal gastrostomy feeding tubes.

PMID- 10957930
TI  - Management of idiopathic achalasia: short-term and long-term outcomes.
AB  - This article reviews current trends in management of esophageal achalasia,
      highlighting short-term outcome and cost comparisons of three treatments:
      botulinum toxin injection, pneumatic dilation, and laparoscopic myotomy. The
      quality of life resulting from these palliative treatments is also discussed, as
      are long-term outcomes.

PMID- 10957931
TI  - Recent developments in chest pain of undetermined origin.
AB  - The syndrome of angina-like pain with normal epicardial coronary vessels is a
      very common and expensive clinical problem. Patients suffering from this
      condition frequently present a diagnostic challenge. Cardiac and musculoskeletal
      disorders must be excluded prior to identifying the esophagus as the source of
      pain. The term "chest pain of undetermined origin" (UCP) has been proposed to
      refer to this condition. Esophageal dysmotility was previously considered a major
      source for chest pain; however, recent studies indicate that esophageal reflux is
      the most common cause of esophageal pain. Two controlled trials of acid
      suppressive agents in patients with chest pain have shown that omeprazole
      provides effective pain relief for the majority of these individuals. Visceral
      hyperalgesia and psychologic disturbances are also commonly noted in patients
      with UCP. Much remains to be learned about the etiology of visceral hyperalgesia
      and the precise role of psychologic abnormalities in these patients. Until
      further information is available, treatment with imipramine or trazodone has been
      shown to offer effective relief of chest pain for subgroups of patients with UCP.
      Psychologic intervention is also valuable in the management of some patients.
      Studies of other therapeutic regimens continue to be conducted.

PMID- 10957932
TI  - Diagnosis and management of supra-esophageal complications of reflux disease.
AB  - Supra-esophageal reflux disease may be manifested in numerous ways, including
      reflux laryngitis, chronic cough, chronic sinusitis, and dental enamel loss. The
      mechanisms of pharyngeal and laryngeal reflux are not clearly defined, and
      standard reflux testing does not consistently demonstrate supra-esophageal
      reflux. The diagnosis is usually based on clinical suspicion when other causes of
      symptoms are not found and on the patient's response to empiric acid suppression.
      With the development of triple-probe pH monitoring, through which pharyngeal pH
      can be assessed along with esophageal pH, the physician may now be able to
      demonstrate pharyngeal reflux in relation to patient symptoms. Therapy consists
      primarily of behavioral modification and aggressive acid suppression, although
      some alternative therapies exist.

PMID- 10957933
TI  - Chronic cough, asthma, and gastroesophageal reflux.
AB  - Gastroesophageal reflux disease (GERD) causes chronic cough and triggers asthma.
      Mechanisms of reflux-associated chronic cough include micro- and macroaspiration,
      laryngeal injury, and a vagally mediated reflex. An empiric trial of a proton
      pump inhibitor in patients without other etiologies of cough found through
      diagnostic testing may be an effective diagnostic strategy for GERD-associated
      cough. In GERD-associated asthma, there is evidence of neurogenic inflammation.
      Medical or surgical therapy of GERD results in asthma symptom improvement in
      about 70% of patients. A 3-month empiric trial of omeprazole, 20 mg daily,
      followed by esophageal pH testing in drug nonresponders, is the most cost
      effective way of diagnosing asthma triggered by GERD.

PMID- 10957934
TI  - Iatrogenic esophagitis.
AB  - A variety of medications have been reported to cause esophageal injury. Nearly
      1000 cases have probably been described in the past 30 years, and this is a vast
      under-representation. Pill-induced esophageal injury is also associated with many
      underlying esophageal diseases. This review addresses the etiology, diagnosis,
      and clinical features of pill-induced esophageal injury as well as the specific
      medications that have been reported to cause it. Ways to prevent esophageal
      injury, including better instructions to patients who are prescribed such
      medications, are also discussed.

PMID- 10957935
TI  - Advances in the management of pediatric constipation.
AB  - Constipation in children is a common concern. There is no single treatment; many
      children do not respond and continue to have chronic problems. This lack of
      response is multifactorial, but it is most likely related to the fact that the
      exact pathophysiology of constipation in children is not known. Diagnostic
      criteria (Rome II classification) and algorithms proposed by the North American
      Society for Pediatric Gastroenterology and Nutrition (NASPGN) for evaluation and
      treatment of children with constipation were recently published and are
      summarized here. The effectiveness of new treatments such as dietary
      interventions, prokinetic agents, biofeedback, and polyethylene-glycol
      electrolyte (PEG) solutions is discussed in this review.

PMID- 10957937
TI  - Recent advances in the diagnosis and treatment of pediatric inflammatory bowel
      disease.
AB  - The diagnosis and management of inflammatory bowel disease (IBD) in children and
      adolescents is a challenge to patients, their families, and to the healthcare
      team. This review highlights recent advances in the epidemiology, diagnosis, and
      management of pediatric IBD. Among the most prominent advances are the new
      diagnostic serologic assays that can help screen for IBD in the absence of
      physical signs of disease and help discriminate between ulcerative and Crohn's
      colitis. Other tests have been identified as potential noninvasive markers of
      disease activity, including color Doppler abdominal ultrasound and sugar
      permeability tests. Recent advances in pharmacogenetics afford clinicians the
      ability to optimize and individualize therapy using azathioprine or 6
      mercaptopurine. Finally, bone health has come forth as a major issue in the
      complete management of pediatric IBD.

PMID- 10957936
TI  - Surgical approaches to pediatric defecatory disorders.
AB  - Defecation is one of the most basic of human activities. Problems with evacuation
      of feces have plagued people since the beginning of time. In modern society,
      defecatory disorders are the source of embarrassment, discomfort, and stress.
      Society's lack of openness on this subject forces many people to endure their
      affliction silently. Nevertheless, although these conditions consume significant
      medical resources, little research has been done on their causes and treatment.
      This review summarizes recent developments in surgical treatment of children with
      these disorders, either in the ability to pass stool or the ability to control
      defecation.

PMID- 10957938
TI  - New developments in total parenteral nutrition for children.
AB  - The field of parenteral nutrition continues to evolve along two major paths:
      prevention of complications and refining of nutritional needs. Parenteral
      nutrition-associated liver disease remains a vexing problem. No single factor is
      to blame; rather, it requires a number of "hits." In the infant, the liver
      disease primarily appears to be related to prematurity of bile flow and
      production, infection, lack of enteral feedings, and most recently appreciated,
      perhaps free radicals. We are able to meet the nutritional needs of our patients,
      but our knowledge of actual nutritional requirements remains incomplete. Future
      studies need to define better appropriate intakes and to rigorously test the
      utility of proposed nutrients such as glutamine.

PMID- 10957940
TI  - [Association of Anatomists Centenarial. 81st Congress of the Association of
      Morphologists. Paris, France, May 7, 1999. Proceedings].

PMID- 10957939
TI  - Intraluminal impedance: an ideal technique for evaluation of pediatric
      gastroesophageal reflux disease.
AB  - Gastroesophageal reflux (GER) in infants becomes gastroesophageal reflux disease
      (GERD) through association with distinct clinical symptoms. Monitoring of pH is
      considered the standard diagnostic tool through which episodes of acidity can be
      detected. Apparently, however, the major amount of GER occurs in the physiologic
      esophageal pH range, which is concealed to pHmetry. Intraluminal impedance is a
      new method for pH-independent detection of esophageal bolus movement. Long-term
      measurements and combination with other diagnostic methods, e.g., pHmetry or
      polygraphic recordings, are possible. Intraluminal impedance has proved
      especially useful in diagnosing GER and GERD in infants. It may develop into the
      ideal technique for this group of patients.

PMID- 10957941
TI  - Surgical technologists.

PMID- 10957942
TI  - Perioperative care of the elderly surgical patient.
AB  - Elderly surgical patients undergo approximately 20% or more of all surgical
      procedures in acute care hospitals across the country. Elderly people also are
      more at risk for surgical intervention because of age-related system changes and
      comorbid conditions. In recent years, greater knowledge about aging and advanced
      surgical, anesthetic, and monitoring technology has made it possible for many
      elderly people to undergo surgery without significant mortality. This article is
      intended to increase the ability of perioperative nurses to anticipate, plan, and
      provide care for their elderly surgical patients.

PMID- 10957943
TI  - Depression, delirium, and dementia in the elderly patient.
AB  - Perioperative nurses commonly care for patients with changes in mental status,
      especially elderly patients. Three common mental status disorders in the elderly
      are delirium, depression, and dementia. Each of the disorders can have similar
      clinical presentations. Despite similarities, the appropriate nursing
      interventions may vary significantly. Interventions discussed in this article
      focus on the etiology of the presenting problem and the nursing interventions
      that will promote the most positive outcome for the patient.

PMID- 10957944
TI  - Evolution of the perioperative clinical nurse specialist role.
AB  - Perioperative nursing roles continue to rapidly change as we enter the twenty
      first century. The need for strong leadership skills, expert clinical skills,
      creative management, ongoing continuing education, and research continues to grow
      in every department of surgical services. The clinical nurse specialist plays an
      important role in addressing each of these needs. Great opportunities exist
      within the field of nursing for perioperative nurses to expand their practice
      using their creativity, ideas, and skills. Using the clinical nurse specialist in
      the perioperative setting can foster creativity, stimulate development of new
      methods based on research, and maximize the delivery of high quality care by the
      entire OR staff.

PMID- 10957945
TI  - Marketing the RN first assistant role.
AB  - Nurses who are educated and certified for the RN first assistant (RNFA) role must
      look for ways to introduce the RNFA role into their health care setting while
      also marketing their services over another assistant's services. This article
      offers information on the RNFA role, including practice requirements, a job
      description, and strategies to help institute the first assistant role into a
      health care facility.

PMID- 10957946
TI  - The pioneer spirit in perioperative advanced practice--two practice examples.
AB  - Perioperative nurses have options in advanced practice instead of leaving the
      acute care setting. One of the newest advanced practice roles is the acute care
      nurse practitioner (ACNP). This role may be ideal for perioperative nurses who
      want to remain in perioperative practice and grow clinically by pursuing advanced
      practice. This article presents two collaborative practice examples for the ACNP
      in the perioperative setting. The authors describe new frontiers in advanced
      perioperative practice and analyze the emerging advanced practice role of the
      ACNP. This challenging and exciting role is well suited to perioperative practice
      in a general and trauma surgery practice. The academic preparation,
      certification, and credentialing necessary to practice as an ACNP are explained.

PMID- 10957948
TI  - Applying the health care industry representative statement to your setting.
      Association of periOperative Registered Nurses.
AB  - AORN values the role our industry partners play in the care of our patients.
      Table 3 is an example of a policy on the health care representative in the OR.
      This article is meant to assist perioperative nurses in writing policies that
      enhance the role of the health care industry representative in the OR, promote
      collegial relationships with an important player on the team, and preserve
      patient safety and privacy.

PMID- 10957949
TI  - Successful reduction of sharps injuries using a structured change process.

PMID- 10957947
TI  - A national study of perioperative nurse education in two technologies.
AB  - In this study, perioperative RNs (n = 122) from hospitals throughout the United
      States were surveyed to explore how and what they initially learned about the
      different types of technology they use in direct patient care and the
      consequences of using these technologies. The study revealed that the most
      frequently identified method participants used to learn technologies (i.e., count
      procedure, electrosurgical unit [ESU]) was via instruction from other staff
      members, and RNs were more likely to learn more facts about the count procedure
      than about the ESU. Although the count procedure was significantly more likely to
      cause stress to RNs (P = .000), an inaccurate count procedure was no more likely
      to result in patient harm than incorrect operation of an ESU.

PMID- 10957951
TI  - Kentucky RN first assistants affect medical legislation.

PMID- 10957950
TI  - A memory box for baby Chandler.

PMID- 10957952
TI  - Finding Internet resources about geriatric issues.

PMID- 10957953
TI  - Preventing surgical site infections--guiding practice with evidence.

PMID- 10957954
TI  - 49th International Congress of the European Society for Cardiovascular Surgery.
      Dresden, Germany, June 24-27, 2000. Abstracts.

PMID- 10957955
TI  - Effects of carbohydrates, ethanol and selected cell wall phenolics on in vitro
      growth of necrotrophic fungi--Heterobasidion annosum and Fusarium avenaceum.
AB  - In this study, a comparative assessment was undertaken of nutritional factors
      that are likely to influence in vivo growth of the S and P-types of necrotrophic
      root rot fungus Heterobasidion annosum and of the damping off pathogen Fusarium
      avenaceum respectively. The results indicate that glucose and fructose but not
      cellobiose or sucrose supported growth of these fungi when used as sole carbon
      source. Particularly for P-types and F. avenaceum, however, the utilization of
      cellobiose and sucrose was considerably enhanced by several fold in the presence
      of ethanol. In addition, key plant cell wall phenolics (ferulic acid, caffeic
      acid, p-coumaric acid) at 0.025% inhibited growth of the test fungi. But this
      toxicity was reversed in the presence of exogenously added cell wall sugars
      (glucose, fructose, sucrose, cellobiose) except for the P-types where sucrose
      addition was apparently slightly effective. Similarly, ethanol whether alone or
      in combination with the phenolics was poorly utilized except for F. avenaceum.
      The importance of these results in understanding factors influencing growth and
      development during pathogenesis of the necrotrophs on their conifer hosts is
      discussed.

PMID- 10957956
TI  - Synthesis, accumulation and hydrolysis of trehalose during growth of peanut
      rhizobia in hyperosmotic media.
AB  - We examined and compared the activities of synthetic and hydrolytic enzymes
      involved in trehalose metabolism, in three peanut rhizobia strains grown in
      control, hypersaline, and non-ionic hyperosmotic media. Results indicated that
      the effects of hyperosmolarity on the synthesis and the degradation of the
      disaccharide were diverse. In the salt-tolerant slow-growing strain
      Bradyrhizobium sp. ATCC 10317, we observed increased synthesis and accumulation
      of trehalose under hyperosmolarity imposed by either NaCl or PEG-8000. In the
      other two peanut rhizobia strains, the disaccharide level did not change under
      hypersalinity. In the salt-sensitive slow-growing strain Bradyrhizobium sp. USDA
      3187, intracellular trehalose diminished in late stationary phase-cells grown
      with PEG, this reduction was accompanied by both an increased activity of
      synthetic enzymes and a decreased activity of trehalase. In the salt-tolerant
      fast-growing strain Rhizobium sp. TAL 1000, we also observed a reduction of
      intracellular trehalose under PEG-mediated growth, this decrease was early and
      transiently accompanied by an enhancement of trehalase activity, afterwards, the
      activity of synthetic enzymes augmented.

PMID- 10957957
TI  - Optimization of the cultivation medium for natamycin production by Streptomyces
      natalensis.
AB  - The effects of certain nutrients on natamycin production by Streptomyces
      natalensis in submerged batch culture were studied. The production of this
      antibiotic required glucose in the cultivation medium with a concentration of 20
      g/l. On the other hand, the highest antibiotic production was obtained in a
      cultivation medium containing 0.05 g/l of potassium dihydrogen phosphate. Further
      increase in phosphate concentration resulted in a significant increase in biomass
      concomitant with lower antibiotic production. Among different N-sources tested,
      only ammonium sulphate, sodium nitrate and beef extract were the suitable
      nitrogen sources in supporting the antibiotic production. Furthermore, a mixture
      of beef extract and yeast extract (8 g/l and 2 g/l, respectively) exhibited a
      synergistic effect in enhancing the natamycin production reaching about 1.5 g/l.

PMID- 10957958
TI  - Effect of D-glucose on induction of xylose reductase and xylitol dehydrogenase in
      Candida tropicalis in the presence of NaCl.
AB  - Xylitol production is suppressed by D-glucose. We previously reported that the
      suppression was abrogated in the presence of NaCl. This was explained in part by
      high levels of xylose reductase (XR) activity. In this study, we investigated the
      effects of D-glucose on XR and xylitol dehydrogenase (XDH) induction in Candida
      tropicalis in the presence of NaCl. We examined the time courses of these
      activities under the following conditions: 50 mg/ml D-xylose, 20-80 mg/ml D
      glucose and 40 mg/ml NaCl. The level of XR increased in the presence of 40 mg/ml
      NaCl, whereas that of XDH was not affected by NaCl. The effects of NaCl upon XR
      and XDH induction suggest that the synthesis of both enzymes is not under a
      coordinate control. The expression of XR is suppressed by D-glucose. In the
      absence of NaCl, suppression continued even after D-glucose was completely
      consumed, while in the presence of 40 mg/ml NaCl, suppression stopped after the
      consumption of D-glucose.

PMID- 10957959
TI  - Abundance of polymers degrading microorganisms in a sea-based solid waste
      disposal site.
AB  - In order to assess the degradability of plastics in solid waste disposal landfill
      sites, microbial populations capable of degrading five kinds of plastic
      constituting polymers, poly epsilon-caprolactone (PCL), polylactic acid (PLA),
      polyethylene glycol (PEG), poly-beta-hydroxybutyrate (PHB) and cellulose acetate
      (CA), in a sea-based solid waste disposal site were investigated. Enumeration of
      aerobic and anaerobic polymers-degrading microorganisms (PDMs) was performed
      against to total 8 leachate samples, which were seasonally collected from the
      facultative pretreatment pond and the aerated lagoon. Both aerobic and anaerobic
      PDMs for natural polymers, PHB and CA, were found in all of the samples, while
      those for chemically-synthesized polymers, PCL, PLA and PEG, could not be always
      detected. In most cases, the ratios of the PHB- and CA-degraders to the
      heterotrophic bacterial population were more than 0.1%. On the other hand, the
      ratios of PCL-, PLA- and PEG-degraders were often much lower. These data indicate
      that the plastics degradation potential is commonly present in the studied
      disposal site, and that the degradation potential for plastics composed of
      chemically-synthesized polymers is inferior to that of natural polymers.
      Population sizes of the PDMs correlated to those of heterotrophic bacteria, and
      the counts of aerobic heterotrophic bacteria and PDMs in the aerated lagoon
      tended to be higher than those of anaerobic ones, indicating that the aeration of
      the leachate resulted in the activation of growth of whole aerobic microbial
      community including the PDMs.

PMID- 10957960
TI  - Solid state cultivation--an efficient method to use toxic agro-industrial
      residues.
AB  - Studies were carried out to screen twelve strains of Lentinus edodes for their
      efficiency to grow on toxic agro-industrial residues of coffee industry in solid
      state cultivation (SSC). Based on best mycelial growth (7.57 mm/day) and biomass
      production (48.78 mg/plate in 12 days at 24 degrees C) in coffee husk extract
      medium, a strain, L. edodes LPB 02 was selected for mushroom cultivation in SSC
      on coffee husk (treated and untreated), coffee spent ground, and a mixed
      substrate comprising coffee husk and coffee spent ground (1:1). SSC was carried
      out under different conditions of moisture and spawn rate. Spawn rate of 10% and
      moisture level of 55-60% was found suitable for all the substrates. Treatment of
      the coffee husk with hot water was found useful for its utilization by the
      fungus. Results showed that there was an increase in the protein content and
      decrease in the fibre content of the substrates after SSC. Fruiting bodies were
      obtained from the treated coffee husk, spent ground and mixed-substrate, and the
      biological efficiency achieved was 85.8, 88.6 and 78.4% for these substrates,
      respectively. However, no fruiting body was obtained with raw coffee husk was
      used as the substrate. Results showed that after SSC, there was a decrease of
      about 27, 40 and 24% in caffeine and about 18, 49 and 12% in tannin contents in
      the treated coffee husk, coffee spent ground and mixed substrate, respectively.
      No caffeine or, tannins were found in fruiting body indicating their degradation
      by the fungal strain.

PMID- 10957961
TI  - The Kluyver effect for trehalose in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae cells are able to grow using trehalose as a sole source
      of carbon and energy. However, the biomass yield obtained with trehalose was
      higher, and the specific growth rate lower, than that obtained with glucose or
      maltose. The respiratory inhibitor antimycin A prevented cell growth on
      trehalose, and no ethanol or glycerol was formed during batch growth on this
      carbon source. Thus, S. cerevisiae exhibits the KLUYVER effect for trehalose:
      this disaccharide is assimilated and respired, but, in contrast to glucose or
      maltose, it cannot be fermented. The high-affinity trehalose-H+ symporter encoded
      by the AGT1 gene is required for growth on trehalose. Analysis of the differences
      in the metabolism of maltose and trehalose (both disaccharides of glucose
      transported by active transport systems) indicated that the absence of trehalose
      fermentation is a consequence of low sugar influx into the cells during growth on
      this carbon source.

PMID- 10957963
TI  - American Society for Mass Spectrometry directory of members.

PMID- 10957962
TI  - The occurrence of yeasts in the forest soils.
AB  - One hundred and eighty one yeast strains were isolated from 180 soil samples
      collected in three types of forest. The samples were taken during one year. The
      yeast species found were similar in spite of distinct forest types. Cryptococcus
      laurentii, Cystofilobasidium capitatum, Leucosporidium scottii, Rhodotorula
      aurantiaca, and Trichosporon cutaneum were the predominant species in both
      deciduous and coniferous forests. The number of yeasts ranged from 1.5 x 10(3) to
      1.1 x 10(4) CFU/g soil. We found that yeasts occurred unevenly in soils during
      the year. The lowest number of yeasts was ascertained in December and the highest
      one in May.

PMID- 10957964
TI  - Repair of A/G and A/8-oxoG mismatches by MutY adenine DNA glycosylase.

PMID- 10957965
TI  - Assays for the repair of oxidative damage by formamidopyrimidine glycosylase
      (Fpg) and 8-oxoguanine DNA glycosylase (OGG-1).

PMID- 10957966
TI  - Detection and quantitation of uracil DNA glycosylase activity.

PMID- 10957967
TI  - Detection of DNA deoxyribophosphodiesterase activity.

PMID- 10957968
TI  - O6-alkylguanine-DNA alkyltransferase assay.

PMID- 10957969
TI  - The E. coli Vsr endonuclease. Assaying activity in vitro and in vivo.

PMID- 10957970
TI  - Coupling of DNA helicase function to DNA strand exchange activity.

PMID- 10957971
TI  - Detection and quantitation of RecBCD enzyme (Exonuclease V) activity.

PMID- 10957972
TI  - Holliday junction branch migration and resolution. RuvA, RuvB, and RuvC from the
      hyperthermophile thermotoga maritima.

PMID- 10957973
TI  - MutS-DNA interactions and DNase protection analysis with surface plasmon
      resonance.

PMID- 10957974
TI  - Flexible genetic engineering using RecA protein.

PMID- 10957975
TI  - Interspecies recombination and mismatch repair. Generation of mosaic genes and
      genomes.

PMID- 10957976
TI  - The use of immobilized mismatch binding protein in mutation/SNP detection.

PMID- 10957978
TI  - Use of uracil DNA glycosylase in scanning for unknown DNA mutations and
      polymorphisms. Glycosylase-mediated polymorphism detection (GMPD-scan).

PMID- 10957977
TI  - Use of uracil DNA glycosylase in the detection of known DNA mutations and
      polymorphisms. Glycosylase-mediated polymorphism detection (GMPD-check).

PMID- 10957979
TI  - The use of resolvases T4 endonuclease VII and T7 endonuclease I in mutation
      detection.

PMID- 10957980
TI  - Cloning neuropeptide tyrosine cDNA.

PMID- 10957981
TI  - Human Y1/Y5 receptor gene cluster. Isolation and characterization.

PMID- 10957982
TI  - Human type 2 neuropeptide Y receptor gene. Isolation and characterization.

PMID- 10957983
TI  - Y4 receptor in different species. Functional expression and binding.

PMID- 10957984
TI  - Neuropeptide Y Y5 receptor expression.

PMID- 10957985
TI  - Homology-based cloning methods. Identification of the NPY Y2, Y4, and Y6
      receptors.

PMID- 10957987
TI  - Neuropeptide Y Y1 receptor-deficient mice. Generation and characterization.

PMID- 10957986
TI  - Developing transgenic neuropeptide Y rats.

PMID- 10957988
TI  - Antisense oligonucleotide approach to study NPY-mediated feeding signal
      transduction.

PMID- 10957989
TI  - A G alpha i RNA-antisense expression strategy to investigate coupling of peptide
      YY/neuropeptide Y receptor to G alpha i.

PMID- 10957990
TI  - NPY Y5 receptor subtype. Pharmacological characterization with antisense
      oligodeoxynucleotide screening strategy.

PMID- 10957991
TI  - NPY antisense oligodeoxynucleotides to study the actions of NPY.

PMID- 10957992
TI  - Localization of Y-receptor subtype mRNAs in rat brain by digoxigenin labeled in
      situ hybridization.

PMID- 10957993
TI  - Central Y4 receptor distribution. Radioactive ribonucleotide probe in situ
      hybridization with in vitro receptor autoradiography.

PMID- 10957994
TI  - Combining non-isotopic localization of NPY mRNA with immunocytochemistry.

PMID- 10957995
TI  - Y receptors characterized by RT-PCR. Distribution in rat intestine.

PMID- 10957996
TI  - Quantification of NPY mRNA by ribonuclease protection assay.

PMID- 10957997
TI  - Radioligand binding studies. Pharmacological profiles of cloned Y-receptor
      subtypes.

PMID- 10957998
TI  - Infertility. Contemporary office-based evaluation and treatment.
AB  - Infertility is a common condition that is highly treatable. Couples can help
      themselves by recognizing that they have a problem, and practitioners can help
      patients by recognizing who requires an infertility investigation and when they
      need it. Instituting a clear and comprehensive evaluation will enable patients
      who need treatment to achieve their goals.

PMID- 10957999
TI  - Contemporary approach to the male infertility evaluation.
AB  - Evaluation of infertile couples has revealed that male factor infertility
      contributes to the problem in up to 50% of cases. Evaluation of the male
      infertility patient may include endocrine studies, sophisticated semen testing,
      and select radiographic studies. Reversible and life-threatening causes of male
      infertility should be identified before proceeding directly to assisted
      reproductive technology. For cases with irreversible causes, a proper evaluation
      can identify patients who may be treated with the breakthrough method of
      intracytoplasmic sperm injection. Many men who were previously thought to be
      infertile may now initiate their own biologic pregnancies. This article
      emphasizes the essentials of the contemporary approach to evaluating the male
      factor in an infertile couple.

PMID- 10958000
TI  - Advances in assisted reproductive technologies.
AB  - Several clinical advances in the field of assisted reproductive technology have
      improved the success rates of IVF. These advances include improvements in
      ovulation induction protocols, the introduction of recombinant gonadotropins,
      GnRH agonists, and, most recently, GnRH antagonists. ICSI has proved to be the
      most successful technique for the treatment of male infertility. The
      micromanipulation techniques developed in the embryology laboratory have
      facilitated advances in the field of preimplantation genetic diagnosis. Years of
      research in embryology laboratories have enabled the successful culture of
      embryos to the blastocyst stage. In the future, blastocyst transfer may have even
      more impact on overall success rates of IVF and multiple pregnancy rates. The
      field of assisted reproductive technologies has come a long way since the first
      successful IVF pregnancy. Future developments are expected to be equally dynamic
      as efforts continue to help couples conceive healthy pregnancies.

PMID- 10958001
TI  - The interpretation and use of statistics in assisted reproductive technologies.
AB  - This article has discussed some of the uses and limitations of currently
      available statistics for ART programs. A well-known example from statistics
      states that flipping a coin will produce "heads" 50% of the time and "tails" 50%
      of the time, provided that the coin is flipped enough times. Experience also
      shows that the result of individual flips cannot be predicted. Similarly, in ART,
      statistics can only give general probabilities and not meaningful predictions of
      the outcome of any particular cycle. Patients should be aware of the limits of
      statistical analysis as it applies to their individual treatment.

PMID- 10958002
TI  - Contemporary issues for spontaneous abortion. Does recurrent abortion exist?
AB  - Most of the time, spontaneous abortion is a random event and represents the
      natural selection process. Although a recurrent factor may be present and may
      cause one or more abortions for a given couple, such instances are rare. Well
      substantiated causes include parental chromosomal abnormalities (e.g.,
      translocation), antiphospholipid syndrome, PCOD, and maternal age greater than 40
      years. Mullerian duplication defects are most likely a cause of pregnancy loss
      for some women. A growing body of evidence refutes the role of corpus luteum
      defect as a common cause of recurrent abortion. Other causes are numerically
      infrequent in occurrence. It is likely that cigarette smoking and alcohol
      consumption contribute to pregnancy wastage. Although some therapies for the
      causes listed herein have been proven effective by randomized controlled trials,
      most have not. Given the excellent outcome demonstrated for most couples with
      unexplained recurrent abortion in the absence of treatment, it is difficult to
      recommend unproven therapies, especially if they are invasive and expensive.
      Instead of examining the environment in which pregnancy has occurred or been
      planned, clinicians have simply counted the number of spontaneous abortions among
      couples in an attempt to determine who should be evaluated. The former approach
      would seem most appropriate and proactive.

PMID- 10958003
TI  - Essential genetics for the obstetrician/gynecologist.
AB  - The science of genetics has become increasingly important in the practice of
      medicine. This article reviews the practical, clinical aspects of genetics
      relevant to obstetrics and gynecology. The basic fundamentals of molecular
      biology techniques currently used in DNA diagnostic tests are discussed.

PMID- 10958004
TI  - New treatments of hyperandrogenism and hirsutism.
AB  - Approximately 5% to 8% of the female population demonstrates some form of
      hirsutism, the presence of prominent facial and body hair caused by excessive
      androgen effect. Treatment methods are classified into three categories: (1)
      hormonal suppression consisting of medical therapy to decrease androgen
      production, (2) the administration of antiandrogens to block the androgen effect
      at the hair follicle, and (3) physical methods of hair removal. Most patients
      require a combination of medical and physical therapy.

PMID- 10958005
TI  - Insulin-lowering medications in polycystic ovary syndrome.
AB  - A growing body of evidence suggests that serum hyperinsulinemia contributes to
      the excess ovarian androgen secretion observed in women with PCOS. As a group,
      women with PCOS are hyperinsulinemic and insulin resistant when compared with
      weight-matched normal women, but not all PCOS subjects display clear metabolic
      defects. The small studies using insulin-sensitizing drugs have demonstrated
      conclusively that a reduction in serum insulin levels is associated with a
      reduction of ovarian androgen secretion in PCOS, providing further evidence that
      hyperinsulinemia contributes to hyperandrogenism by increasing ovarian androgen
      secretion and reducing SHBG. The improvement of serum androgen levels with
      multiple different drug classes with different mechanisms of actions suggests an
      effect mediated by reduction in circulating insulin levels rather than a direct
      ovarian effect of the drugs. Although the studies published to date have
      increased understanding of the pathophysiologic mechanisms of PCOS, before these
      drugs can be recommended as first-line therapy for women, longer term clinical
      trials are needed to compare their safety and efficacy with other established
      therapies, such as oral contraceptive pills and antiandrogens. Because of the
      potential direct and unique beneficial effects of these medications on
      metabolism, studies must be performed to evaluate their efficacy in combination
      with other therapies, especially oral contraceptives. It is likely that subsets
      of patients who cannot tolerate traditional medications will be better managed
      with insulin sensitizers as first-line therapy; however, to date, the optimal way
      to identify these subjects is unknown. Whether therapy should be limited to
      subjects with documented hyperinsulinemia also remains unknown.

PMID- 10958006
TI  - Advances in contraception.
AB  - Many safe and effective contraceptive methods are currently available, and a
      stream of new products is being introduced to the market. This article presents
      the histories, descriptions, and future trends for oral contraceptive pills,
      hormonal implants and injections, and intrauterine devices. Other methods
      discussed include barrier methods, spermicides, and emergency contraception, and
      permanent sterilization.

PMID- 10958007
TI  - Hormone replacement for the new millennium.
AB  - The field of hormone replacement therapy continues to evolve. Guidelines and
      dosing regimens change in response to new data and treatment options. It is
      important for the clinician to remain informed to be able to interpret new
      findings for the patient.

PMID- 10958008
TI  - Premenstrual syndrome. Advances in diagnosis and treatment.
AB  - Premenstrual syndrome and PMDD are increasingly recognized as medical entities
      that adversely affect the quality of life of a subset of women. When research
      criteria or the strict definition of PMDD are used, the prevalence of PMS is
      thought to range from 3% to 5% among reproductive-aged women. Although the
      precise pathophysiology is not known, it is increasingly believed that women with
      PMS have an altered sensitivity of central neurotransmitters, particularly
      serotoninergic, to normal circulating levels of estradiol and progesterone.
      Significant advances have been made in pharmacologic therapy for PMDD, with the
      largest clinical trials demonstrating efficacy of the SSRIs. These studies show
      relief of distressing mood symptoms and improvements in parameters of social
      function in most patients.

PMID- 10958009
TI  - Update on the medical treatment of endometriosis.
AB  - The treatment of women with endometriosis can be a challenge. Therapeutic
      strategies must be tailored to the individual symptoms, age, and desire for
      fertility. Medical therapy continues to be based on endocrine treatment, such as
      oral contraceptives, progestins, danazol, and GnRH agonists. Unfortunately,
      recurrence rates are high after discontinuation of therapy. Recent clinical
      research on GnRH analogues plus add-back therapy has produced favorable results.
      Long-term treatment of patients using this approach has successfully reduced pain
      while minimizing symptoms of hypoestrogenism and adverse metabolic effects, such
      as loss of bone mineral density. Currently, GnRH analogues given with add-back
      therapy seems to be the most effective long-term approach to the treatment of
      symptomatic endometriosis. In the future, other modalities, such as medicated
      vaginal rings, inhibitors of steroidogenic enzymes, and GnRH antagonists, will
      most likely be options.

PMID- 10958010
TI  - An update on the medical treatment of ectopic pregnancy.
AB  - Medical treatment of ectopic pregnancy with methotrexate has been shown to be
      effective and safe in appropriate patients. When considering medical management,
      the definitive diagnosis of an ectopic pregnancy and the assurance that the
      patient is a candidate are of paramount concern. An understanding of the
      mechanism of action and pharmacokinetics of methotrexate allows the clinician to
      better inform patients, recognize and treat side effects, and be cognizant when
      treatment is unsuccessful. Two common protocols, the "multi-dose" and the "single
      dose" protocols, have excellent success rates; however, neither one of these is
      completely effective. The "multi-dose" protocol appears to have a higher success
      rate than the "single-dose" protocol.

PMID- 10958011
TI  - New approaches to the management of fibroids.
AB  - New and innovative treatments are available for the control of uterine
      leiomyomata, each with advantages and disadvantages. Most of these techniques
      have few data to support their use; they are generally poorly studied, with brief
      follow-up. Not much is known regarding risks, costs, and comparative value.
      Furthermore, many of these procedures are in a state of evolution, with current
      investigative results having little applicability to the future use of such
      tools. Given the increasing number of options available to the patient with
      fibroids, further investigation is needed. A series of high-quality, randomized,
      comparative trials are needed to assess the relative merits of these new
      alternatives to treatment.

PMID- 10958012
TI  - Annual meeting of the Swiss Society of Intensive Care, the Swiss Society of
      Pneumology and the Swiss Society of Infections. Lausanne, 15-16 June 2000.
      Abstracts.

PMID- 10958013
TI  - Aboriginal health. Can leadership and innovation make a difference? Part 1.

PMID- 10958014
TI  - Music as medicine--needs functioning receptors?

PMID- 10958015
TI  - Assessment of need for information on illicit drugs in Arabic, Chinese and
      Vietnamese languages.

PMID- 10958016
TI  - The sexual revolution--what has it cost?

PMID- 10958017
TI  - Helping young children with special developmental needs.
AB  - BACKGROUND: Many parents worry about their children's abilities and whether their
      behaviour is normal. The range and complexity of behaviour and skills change
      rapidly in young children with individual patterns of development varying widely.
      Normal stages of development may be delayed or the expected sequence varied. This
      can be associated with neurological or genetic disorders or chronic illness but
      may sometimes reflect a family pattern. Recognition of vulnerability enables the
      child's special needs to be supported before a disorder becomes entrenched.
      Intervention is aimed at understanding and supporting the child, promoting
      success and approval and encouraging appropriate neurobiological development.
      OBJECTIVE: This article aims to: clarify the general practitioner role in
      coordinating appropriate support in collaborative management; describe the
      relative frequency of various developmental problems; describe the range of
      assisting services available; emphasise the importance of early recognition and
      referral; and highlight the interaction between communication disorders and
      behavioural problems. DISCUSSION: The family doctor may be able to identify
      problems early and assist parents in coordinating optimum help for their
      children. Often the GP is the one professional who has known the child from
      infancy and may know other family members with similar problems as well as
      understanding the cultural context. This gives the GP a central role in early
      recognition of developmental vulnerability and in maintaining long term review
      and modification of supports for the child and family.

PMID- 10958018
TI  - Is developmental assessment worthwhile?
AB  - BACKGROUND: There is increasing research evidence that early intervention in a
      range of children's problems can have a positive effect on both children and
      families. There are a number of widely used screening tests available for the
      early detection of children's developmental problems, including the Denver II
      test; however, the routine uptake of these tests has been disappointing. They are
      time consuming; in some instances they require special training, and the general
      practitioner needs to purchase kits containing the required testing items.
      OBJECTIVE: This article looks at how developmental and behavioural disorders can
      be detected early on in the child's development by applying a new screening
      method which is useful in a general practice setting. DISCUSSION: As the focus of
      clinical practice moves more to prevention and early intervention, GPs are likely
      to become more involved with the early detection of developmental problems.
      Recently a new test--the Parents' Evaluation of Developmental Status (PEDS) has
      been developed. It requires parents to complete a 10 item questionnaire which the
      GP can then score and interpret according to a predetermined algorithm. The PEDS
      is simple and quick, and is thus ideal for the busy GP and has similar
      psychometric properties to other developmental screening tests. It also has the
      distinct advantage of actively involving parents in the process.

PMID- 10958019
TI  - Eating and nutritional problems in children.
AB  - BACKGROUND: In Australia good food is abundant and relatively cheap but childhood
      obesity is increasing and many children are offered suboptimal nutrition.
      OBJECTIVE: The impediments to healthy food choices and strategies for promoting a
      healthy diet in childhood are discussed. DISCUSSION: Good nutrition in childhood
      is important, not only for the health, growth and development of the child but
      also for long term health. A child's energy requirement can easily be met from
      snack food, at the expense of more nutrient rich foods. There are no 'good' or
      'bad' foods: it is the overall package of intake that is important. Children need
      to be offered a variety of nutrient rich foods at regular times during the day.

PMID- 10958020
TI  - Assessment of the child with recurrent respiratory infections.
AB  - BACKGROUND: Children with atopy, daycare attendance, crowding or exposure to
      cigarette smoke are predisposed to recurrent respiratory infection. The young
      child who 'is always sick' is a common problem, creating concern for their
      parents and doctors. OBJECTIVE: To outline an approach for determining which
      children with recurrent respiratory infections are normal, which have an allergic
      disorder and which have an underlying immune or other problem. DISCUSSION: The
      majority of children with recurrent respiratory tract infections are normal,
      however, it is important to consider atopy and underlying immunodeficiency. In
      those children where there are features suggesting an underlying immunological
      disorder, specialist assessment is warranted.

PMID- 10958021
TI  - Postmenopausal osteoporosis treatment guidelines.
AB  - BACKGROUND: Several years ago, Osteoporosis Australia published Guidelines for
      the management of osteoporosis. Since then significant advances in our
      understanding of the treatment of osteoporosis have been published. The
      importance of this is heightened as early diagnosis is now possible with precise
      methods of bone density measurement. OBJECTIVE: This article presents updated
      guidelines developed on behalf of Osteoporosis Australia for the treatment of
      postmenopausal osteoporosis to help general practitioners identify those women at
      risk and to review current treatment strategies. DISCUSSION: Osteoporosis and its
      associated problems are major health concerns in Australia, especially with an
      ageing population. While important principles of management are still considered
      to be maximising peak bone mass and prevention of postmenopausal bone loss by
      oestrogen therapy, new clinical trial data about drugs such as raloxifene and the
      bisphosphonates have recently become available and the relative role of various
      agents is gradually becoming clearer.

PMID- 10958022
TI  - Exercise recommendations for osteoporosis. A position statement of the Australian
      and New Zealand Bone and Mineral Society.
AB  - BACKGROUND: Individuals diagnosed with osteoporosis have a high risk of skeletal
      injury. Regular physical activity may contribute to preventing osteoporosis, but
      the efficacy of exercise intervention once the disease is established has not
      been rigorously investigated. OBJECTIVE: To provide recommendations focusing
      specifically on exercise goals for osteoporosis, taking into account evidence for
      maximisation and maintenance of bone strength and minimisation of trauma, and to
      identify the levels of evidence that support this. DISCUSSION: The primary
      benefit of exercise for adult bones is conservation, not acquisition. In elderly
      individuals, improved fitness and muscle strength contribute to the prevention of
      falls and a lower risk of fracture. Physical activity may also reduce the rate of
      bone loss. Exercise goals for osteoporosis should include pain reduction,
      increased mobility and improvements in muscle endurance, balance and stability.
      These are worthwhile end points because not only may they prevent falls but they
      may improve the quality of life. In conjunction with advice to increase dietary
      calcium, exercise plays a significant part in a lifestyle prescription for
      reducing fractures in later life. In postmenopausal women, although less
      effective than oestrogen for maintaining bone mineral density, exercise should be
      regarded as part of an overall treatment strategy.

PMID- 10958023
TI  - Osteoporosis and men. Don't forget the blokes.
AB  - BACKGROUND: There is a clear analogy between osteoporosis and hypertension. After
      all, the fractures associated with osteoporosis can be as disastrous as a
      cardiovascular event associated with hypertension and both fractures and
      cardiovascular events, can be greatly reduced by modern treatment. However,
      osteoporosis is still relatively underdiagnosed, especially in men where it may
      not be considered an important aspect of men's health. OBJECTIVE: This case study
      may trigger readers to look for osteoporosis in men at risk and to use the
      available medications and interventions to preserve bone and avoid falls in such
      men, thus reducing fractures and associated disability and pain. DISCUSSION: The
      risk factors for osteoporosis and fracture are known and easily identified and
      measurement of bone mineral density quantifies bone loss and fracture risk. There
      are well established strategies to protect bone, to prevent fractures and to
      maintain comfort. Osteoporosis is already a major public health problem in
      Australia and will become more important as the proportion of old and the 'old
      old' increase over the next two decades. Osteoporosis is recognised as an
      important component of the health of older women and should not be forgotten in
      older men.

PMID- 10958024
TI  - Respiratory tract infections and antibiotics.

PMID- 10958025
TI  - Pathology quiz. A persistent itchy papulovesicular rash.

PMID- 10958026
TI  - Radiology quiz. How can hepatic metastases be evaluated?

PMID- 10958027
TI  - Heart and soul.

PMID- 10958029
TI  - WISDOM. Will Australian women participate?
AB  - AIM: This study investigated the likelihood of 50-69 year old women participating
      in the Women's International Study of long Duration Oestrogen after Menopause
      (WISDOM)--a 10 year randomised placebo controlled trial of hormone replacement
      therapy involving 10 years treatment plus a further 10 years follow up of major
      health outcomes. METHODS: The Health Monitor 2 (a representative population
      telephone survey) was used. Participants were 268 women aged 50-69 years from a
      total survey population of 2003 adults. Sociodemographic characteristics were
      collected. RESULTS: Of the women surveyed 20.9% indicated they were likely to
      participate and this was independent of sociodemographic characteristics and self
      reported health status. Women aged 50-54 were more likely to participate than
      older women. DISCUSSION: After allowing for exclusion criteria, it is estimated
      that approximately 10% of 50-69 year old women approached for recruitment in
      WISDOM may actually participate. There are likely to be sufficient altruistic
      women in this population to run WISDOM in Australia.

PMID- 10958028
TI  - What is WISDOM and why should Australia participate?

PMID- 10958030
TI  - Computer education. Don't forget the older GPs.
AB  - OBJECTIVE: To implement and evaluate a computer education and support program for
      GPs. METHODS: A 'hands-on' curriculum, based on small group learning in a
      clinical computing laboratory and supported via the Internet, was developed and
      implemented. Evaluation was threefold: observations during lessons; interviews;
      and participants completing a questionnaire before and six months after the
      course. A randomly selected group of GPs from the same region completed a
      modified version of the 'before' questionnaire at the same time as participating
      GPs were completing their six month questionnaire. Participants included 128 GPs
      in a computer education program in Victoria (Australia) plus 127 'control' GPs.
      Outcome measures were self reported computing skill, attitudes to and actual use
      of clinical applications. RESULTS: Six months after training, there was a
      significant increase in self reported computer skill (p < 0.01). Multivariate
      regression found that, after controlling for gender, practice characteristics,
      and previous training, the older (> 55 years) GPs reported greater change in
      their skills than their younger colleagues. The increased skill happened
      regardless of which or how many modules were completed, and included use of
      email, the Internet, computers for research and electronic prescribing. Awareness
      of relevant computer applications, confidence with computers and intention to use
      applications also increased. Participants found the dedicated clinical computing
      laboratory useful; however, there are significant issues with maintenance and
      keeping systems up-to-date. CONCLUSIONS: The computer education and support
      program was relevant to GP needs, deliverable and effective in improving skills
      and utilisation. Divisions and other GP organisations should be assisted to
      establish similar education and support programs and, perhaps, target older
      doctors.

PMID- 10958031
TI  - Handling information. Some ethical issues.
AB  - BACKGROUND: General practitioners are increasingly involved in a range of
      activities which require the use of data from patients' case notes. These
      activities include audit, evaluation and research. Any use of patient data has
      the potential to breach patient confidentiality and privacy. However, at present
      the requirements in terms of obtaining informed consent vary. Research is usually
      acknowledged as requiring consent, but this is not always the case for audit and
      evaluation activities. OBJECTIVES: The aim of this paper is to define audit,
      evaluation and research activities in general practice and to clarify the ethical
      issues involved in using patient data for these purposes. We argue that the
      ethical issues raised by accessing patient case notes are similar for all of
      these activities. DISCUSSION: The ethical obligation to obtain patient consent
      prior to accessing or using patient information is the same for many general
      practice audit, evaluation and research activities. However, the avenues for
      obtaining ethical clearance may be hard to access for GPs. In addition, the
      special relationship between patients and their GP and the requirements specified
      by health research ethics committees such as de-identification of case notes
      create problems for these activities in general practice.

PMID- 10958032
TI  - [The renin-angiotensin system--structure, function and therapeutic control].

PMID- 10958033
TI  - [Peripheral angiotensin II receptor blockers in clinical practice--
      possibilities, indications and perspectives].

PMID- 10958034
TI  - Bone grafting techniques in treating fracture nonunion.
AB  - A fracture nonunion is not uncommon and the principle of treatment has been well
      established. Traditionally, for the efficacy of treatment, a nonunion is
      classified as a hypervascular (hypertrophic) or an avascular (atrophic) type.
      Methods for treating nonunion are multiple and bone grafting techniques have been
      the most convincing and widely used. Bone grafts can be divided into allografts
      and autografts and cortical or cancellous bone grafts; each has its individual
      function. However, both types of a nonunion need to be supplemented with
      cancellous bone graft to increase the rate of success. Basically, effective
      treatment should include making fracture gaps vanish, providing sufficient
      stability, and initiating osteogenic power. Clinically, use of the closed bone
      grafting technique is preferable when possible. However, the critical size for
      using the closed technique to treat segmental bony defects has yet to be defined,
      and the open technique should be utilized whenever the effectiveness of the
      closed technique is in doubt. To simplify the surgical procedure and to reduce
      morbidity at the donor site, bone graft substitutes should be continuously
      investigated.

PMID- 10958035
TI  - Cardiac arrest induced by accidental inhalation of anoxic gases, is the cause
      always a lack of oxygen?
AB  - BACKGROUND: We experienced a case of accidental administration of 100% carbon
      dioxide (CO2) during anesthesia, which resulted in cardiac arrest. After
      successful cardio-pulmonary resuscitation the child recovered without brain
      damage. This outcome was quite different than that of the more commonly reported
      accidental administration of 100% nituous oxide (N2O), as the latter usually
      results in death from cerebral damage rather than cardiac arrest. We speculated
      that the cause of death and/or cardiac arrest may differ between these two anoxic
      gases. METHODS: Fourteen dogs were anesthetized and divided into two groups to
      receive either 100% CO2 or 100% N2O. Blood pressure (BP), heart rate (HR),
      cardiac output (CO), dp/dt, pulmonary artery pressure (PAP), central venous
      pressure (CVP) and blood gases (BG) were measured every 30 seconds until cardiac
      arrest (CA) occurred. RESULTS: The CO2 group showed a rapid decline in BP, HR,
      dp/dt, CO, pH, and PaO2 and a rise in PAP, CVP, and PaCO2, with CA occurring at
      119 +/- 41 seconds. At the time of CA, the BG values were pH 6.6 +/- 0.09, PaCO2
      375 +/- 69, and PaO2 62 +/- 15 mm Hg. The N2O group maintained BP, HR, dp/dt, pH,
      PaCO2, and experienced a rapid decline in PaO2 as in the CO2 group until 180
      seconds, at which time the PaO2 was 12.3 +/- 3 mm Hg. CA occurred at 390 +/- 52
      seconds. The values for pH, PaCO2 and PaO2 were 7.5 +/- 0.05, 25 +/- 15 and 4.8
      +/- 1 mm Hg, respectively, at the time of CA. CONCLUSION: One hundred percent CO2
      induced cardiac arrest occurred in 119 seconds and was not oxygen-dependent,
      whereas 100% N2O induced cardiac arrest occurred in 390 seconds and was clearly
      dependent on hypoxemia.

PMID- 10958036
TI  - Balance evaluation in hemiplegic stroke patients.
AB  - BACKGROUND: Decreased equilibrium in standing and walking is a common problem
      associated with hemiplegic stroke patients. Stroke patients with balance problems
      are prone to falls. In addition to spatial recognition, the appropriate pattern
      of muscle activity to preserve balance depends on sensory and motor processes.
      Previous reports have mentioned that the right posterior parietal cortex seems to
      be predominantly involved in spatial integration. We therefore wanted to conduct
      a study to quantify and compare the balance control between right hemispheric
      stroke and left hemispheric stroke patients. METHODS: Thirty hemiplegic stroke
      patients (14 right, 16 left) and 15 age-matched healthy subjects were included in
      this study. The objective measurement of the basic components of balance control
      was performed using the SMART Balance Master. The motor status of the hemiplegic
      limbs was evaluated by Brunnstrom staging. The functional outcome of the stroke
      patients was evaluated by the functional independence measure (FIM). RESULTS: The
      balance function of stroke patients was significantly worse as compared to that
      of the healthy subjects especially in dynamic stability. However, different from
      the other reports, our right hemispheric stroke patients had better balance
      function than our left hemispheric patients. The locomotion and mobility scores
      of the FIM were also better in the right hemispheric stroke patients. CONCLUSION:
      This result suggested that the motor function of the healthy limbs of stroke
      patients may play an important role in their balance function. The results of
      this study may provide a guide for prescribing a more efficient rehabilitation
      program for stroke patients.

PMID- 10958037
TI  - Age related testosterone level changes and male andropause syndrome.
AB  - BACKGROUND: Much like the menopause syndrome occurring among older women, a
      similar condition has been defined among men. Testosterone production increases
      rapidly at the onset of puberty, then dwindles quickly after age 50 to become 20
      to 50% of the peak level by age 80. Many men older than age 50 have experienced
      frailty syndrome, which includes decrease of libido, easy fatigue, mood
      disturbance, accelerated osteoporosis, and decreased muscle strength. We
      investigated serum total testosterone levels and andropause syndrome in men.
      METHODS: Serum total testosterone levels were measured in 53 symptomatic men
      older than age 50 and in 48 men younger than age 40 for a control group. We also
      analyzed andropause symptoms among the 53 men older than age 50. RESULTS: The
      mean serum total testosterone level in the symptomatic men older than age 50
      (mean: 2.68 +/- 0.51 ng/ml, range: 1.21 to 4.13 ng/ml) was significantly lower
      than that in the control group (mean: 7.01 +/- 0.82 ng/ml, range: 5.53 ng/ml to
      8.14 ng/ml). Male frailty syndrome in these men older than 50 included: decreased
      libido (91%), lack of energy (89%), erection problems (79%), falling asleep after
      dinner (77%), memory impairment (77%), loss of pubic hair (70%), sad or grumpy
      mood changes (68%), decrease in endurance (66%), loss of axillary hair (55%), and
      deterioration in work performance (51%). CONCLUSION: The serum total testosterone
      level showed a decline with aging, especially in the men older than age 50. Low
      serum testosterone levels were also associated with the symptoms of male
      andropause syndrome.

PMID- 10958038
TI  - Quantitative measurement on three-dimensional computed tomography: an
      experimental validation using phantom objects.
AB  - BACKGROUND: The use of 3-dimensional computed tomography (CT) imaging has been
      applied to the craniofacial region as well as to many other parts of the human
      body. Quantitative measurements have frequently been performed on the 3
      dimensional images. However, critical validation of the measurement has been
      insufficient in the literature. This study was designed to evaluate the errors of
      the 3-dimensional measurements. METHODS: Four phantom objects, a cube, a sphere,
      a cylinder, and a life-size adult skull model, were scanned using standard CT
      acquisition protocol. The data were transferred, reformatted, and displayed on an
      IBM-compatible personal computer running AnalyzePC 2.5 software. Linear, area,
      and volume measurements were obtained using one of the two methods. The first was
      physical measurement of the phantom objects using a caliper for linear
      measurement and mathematical calculations for area and volume measurements. The
      second was done by computer measurement on 3-dimensional images using the
      AnalyzePC 2.5 program. Each measurement was performed twice. The differences were
      compared between the repeated measurements and between the two methods. RESULTS:
      The images were displayed according to standard 3-dimensional CT protocol. The
      differences between the measurements were insignificant and ranged from 0.00 to
      2.57%. CONCLUSION: This study validated the accuracy of the quantitative
      measurements on 3-dimensional CT images.

PMID- 10958039
TI  - Correction of a migrated Tenckhoff peritoneal dialysis catheter using a
      Lunderquist guidewire: report of two cases.
AB  - Two chronic ambulatory peritoneal dialysis (CAPD) patients who experienced from
      ultrafiltration failure resulting from malposition of a Tenckhoff catheter were
      treated. Conservative management such as changing body position, saline infusion,
      and enemas had been tried, but had failed. To avoid surgical intervention, we
      attempted to correct the malposition using a 120-cm-long Lunderquist guidewire
      (Nycomed, NY) with a 15-cm-long soft and flexible tip at its distal end. Under
      fluoroscopy, we successfully repositioned these two migrated Tenckhoff catheters
      using a Lunderquist guidewire. To the best of our knowledge, this is the first
      report of using a Lunderquist guidewire to correct a malfunctioning Tenckhoff
      catheter in CAPD patients. The Lunderquist guide wire has the advantages of being
      relatively non-invasive and easily used and it provides a reduced morbidity rate.
      Moreover, using this guidewire allows the Tenckhoff catheter to produce torque
      and whiplash, buckling, sweeping and rotating maneuvers that can help to correct
      malposition of the catheter and redirect the catheter to its ideal position. We
      therefore suggest that patients who receive surgical revision for a
      malfunctioning Tenckhoff catheter have at least one attempt at correction using
      this safe and easy procedure before surgery.

PMID- 10958040
TI  - Rationale for directional atherectomy and adjunctive stenting in a patient with
      non-Q wave myocardial infarction.
AB  - The development of percutaneous transluminal balloon angioplasty (PTCA) is the
      greatest revolution in the management of stenotic coronary artery disease.
      However, PTCA is limited in its application to some specific subgroups of complex
      lesions such as bifurcational, ostial and plaque burden lesions. For this reason,
      some new strategies including directional atherectomy (DCA) have been developed
      as advanced modalities in the treatment of these complex lesions, which if
      treated by PTCA would certainly yield poor outcomes. We report a case of non-Q
      wave myocardial infarction resulting from obstruction of the ostium of left
      anterior descending artery. DCA and adjunctive stenting to the lesion were
      successfully performed and the patient was discharged uneventfully after the
      procedure. We suggest that DCA is a striking method and has much merit in the
      treatment of complex lesions with a high rate of success. In view of
      consideration of restenosis remains an importantly unresolved problem in
      percutaneous coronary intervention in specific subgroups of complex lesions. In
      the future, adequate debulking by mean of DCA in combination with adjunctive
      stenting which recently emerges as a promising treatment in the prevention of
      restenosis may provide a more consistent and attractive method for prevention of
      restenosis in these complex lesions.

PMID- 10958041
TI  - Pseudomelanosis duodeni: case report.
AB  - Pseudomelanosis duodeni is a rare benign condition. It manifests endoscopically
      as discrete, flat, small brown-black spots in the duodenal mucosa. It produces no
      symptoms and may be reversible. The cause and natural history of the pigmentation
      have not been clarified, although it is associated with a variety of systemic
      illnesses and medications. With electron microscopy and electron-probe energy
      dispersive X-ray analysis, the pigment corresponds principally to an accumulation
      of ferrous sulfide (FeS) in macrophages within the lamina propria. We report the
      case of a 56-year-old female patient with a past history of diabetes mellitus and
      hypertension. She was admitted because of nausea, vomiting, and diarrhea and
      underwent esophagogastroduodenoscopy because of stool occult blood test results
      of 3+. Endoscopy revealed diffusely scattered black spots in the bulb and second
      portion of the duodenum. Histological examination showed numerous pigment-laden
      macrophages in the lamina propria of mucosal villi. The diagnosis requires
      further confirmation by electron microscopy and electron-probe energy dispersive
      X-ray microanalysis. No special therapy is indicated for this rare lesion.

PMID- 10958042
TI  - Topical ocular anesthetic abuse: case report.
AB  - Topical ocular anesthetic abuse is uncommon in our clinical experience. The
      complications associated with topical ocular anesthetic abuse included persistent
      corneal epithelial defect, ring-shaped stromal infiltrate, and anterior segment
      inflammation. This disorder can masquerade as Acanthamoeba keratitis or other
      infectious keratitis. We report a suspicious case of infectious keratitis
      unresponsive to antibiotics. The patient had an irritable manner, low pain
      control threshold, and an analgesic drug abuse history. This information, along
      with finding a topical ocular anesthetic bottle at bedside helped alert us to
      possibility of drug abuse. After discontinuing use of the topical anesthetic and
      using lubricants, topical steroid, and a therapeutic soft contact lens, the
      condition improved.

PMID- 10958043
TI  - [Prophylactic treatment of hemicrania].

PMID- 10958044
TI  - [Thermomagnetic bandages and belts in neck and lumbar pain syndrome].

PMID- 10958045
TI  - [Methodology for the ethical assessment of a clinical case].
AB  - The ethical evaluation of a clinical case is the application of general ethical
      principles to a real situation. Epicheia and Prudence are required to realized
      this goal. The moral sources of an human action are: a) the object of the action;
      b) the agent's intentions; c) general conditions. In this way, the ethical
      evaluation requires: a) the appropriate knowledge of the medical action; b) the
      knowledge of the ethical principles; c) the evaluation of the agent's intentions;
      d) to consider the global relational reality.

PMID- 10958046
TI  - Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo
      controlled study.
AB  - OBJECTIVE: Gabapentin is an antiepileptic drug of new generation that increases
      brain GABA levels. We report the results of a three-month randomised double-blind
      placebo-controlled study on the effects of gabapentin in the prophylaxis of
      patients with migraine meeting the IHS criteria. PATIENTS AND METHODS: We treated
      63 patients suffering from migraine with or without aura. Patients treated their
      attack at home using symptomatic drugs and clinical assessment was recorded on a
      diary. After a washout of 8 week from any other prophylactic treatment, all
      patients were treated with 1200 mg/day of gabapentin; this is our therapeutic
      plan: 400 mg/day from 1st to 3rd day, 800 mg/day from 4th to 6th day and 1200
      mg/day from 7th day. RESULTS: No patients withdrew, gabapentin was well
      tolerated; adverse events (somnolence, dizziness, tremor, fatigue and ataxia)
      generally were transient and mild to moderate in severity and in 13 patients
      (27%) only occurred. At the end of treatment, in such case, we reported a
      significative reduction of frequency and intensity of migraine in 30 patients
      treated with gabapentin. DISCUSSION: Our observations indicate that gabapentin is
      well tolerated by patients and that reduces headache frequency and use of
      symptomatic drugs in both groups. Gabapentin shows to have an effective
      therapeutic action in the prophylactic treatment of migraine.

PMID- 10958047
TI  - [Use of thermomagnetic bandages and belts in cervical and lumbar pain syndromes.
      Experimental study with double blind method versus placebo].
AB  - OBJECTIVE: To assess the antalgic activity of thermomagnetic bandages and belts
      in cervical and lumbar pain syndrome (respectively CPS and LPS), compared with
      non-magnetic devices (placebo). PATIENTS AND METHODS: It was a double-blind study
      on two groups of 30 patients suffering from chronic back pain (15 cervical and 15
      lumbar in each group). Patients had to stop any previous analgesic or
      antiinflammatory drug treatment at least 8 days prior to entering the study. Each
      subject included in the study had to wear the bandage/belt for 8 hours a day for
      14 consecutive days. Before the start, every subject underwent an initial
      assessment of his/her current pain level and functional status through the use of
      two visual analogue scales (pain and functional status) and one verbal scale
      (pain). After the end of the study, a final assessment was made using the same
      tools. RESULTS: 93 and 97% (respectively in the CPS and LPS group) were the
      percentages of patients in the actively-treated arm who showed an improvement
      both in pain level and in functional status. This improvement was statistically
      significant vs. the correspondent placebo-treated groups (respectively, 20 and
      23% in the CPS and in the LPS). No adverse events associated to treatment were
      signalled. CONCLUSIONS: The use of thermomagnetic bandages and belts (which are,
      virtually in all cases, free of contraindications) allows us a more rational and
      easy management of the patient suffering from chronic back pain.

PMID- 10958048
TI  - [Priority objective of medical education].
AB  - PURPOSE: To analyze the Best Evidence Medical Education approach (BEME) in
      relation to the need of improving the quality of education in medical faculties
      through strictly controlled forms of experiments. MATERIALS AND METHOD: Starting
      from the analysis of several Medical Education Centers in different Faculties of
      Medicine, their objectives, activities and quality control systems have been
      extrapolated in order to point out how institutions identify and control
      introduced changes. More in detail, a comparison between two italian Centers for
      Medical Education has been carried out: the one of Bari, which has been the first
      one in Italy, and the most recent one, at the Campus Bio-Medico, in Rome.
      CONCLUSIONS: A tendency to apply the growing cultural acquisitions and the new
      criteria of economy and management to the medical field is developing, which asks
      for a particular attention to the quality control and to the cost-benefit
      analysis. Evidence based medicine tries therefore to validate the diagnostic and
      therapeutic decisions on the basis of experiments whose methodology belongs to
      the controlled clinical trials' model. These, despite some blind areas, are still
      a shared effort of the scientific community to objectify the analysis of a given
      problem and compare the results. Likewise, Evidence Based Medical Education is an
      attempt to maintain the need for experimenting effective educational forms
      without giving up their scientific validation. The Medical Education Centers in
      the different Faculties may have this research function which makes undergraduate
      medical education one of the three main aspects of the medical teacher's role:
      research, care and education.

PMID- 10958049
TI  - [Maternal smoking in pregnancy].
AB  - OBJECTIVE: In the last years has been a progressive increase of tabagism in the
      female sex. This study wanted to examine the influence of the pregnancy on
      voluntary practices and especially on smoking. PATIENTS AND METHODS: 140 women
      with a mean age of 33.05 years and with a mean gestational age of 28.56 weeks
      (range 5-42) were interviewed. Each one received a questionnaire about social and
      psychosocial status, a schedule about style of living (CAGE), a questionnaire
      "How much do you drink" (from SQQ) and a series of questions about smoking.
      RESULTS AND CONCLUSIONS: Our study suggests that the tabagism decreases in the
      greatest part of pregnant women, and them increases again after child birth.
      Pregnancy gets women both to finish and to decrease smoking apart from social
      status and any variant contemplated.

PMID- 10958051
TI  - [Some light at the end of the tunnel in the prevention and treatment of herpetic
      neuritis].

PMID- 10958052
TI  - [New guidelines in the treatment of congestive heart failure].

PMID- 10958050
TI  - [In vitro effects of L-carnitine on the inhibition of sperm mobility induced by
      FANS].
AB  - OBJECTIVE: We wanted to study the function of some substances present in the
      seminal fluid (PG and L. Carnitine), which, with different mechanisms, affected
      Spermatozoa motility, and to study the effect of other substances (F.A.N.S.),
      known also for their action on P.G. PATIENTS AND METHODS: Ten samples of seminal
      fluid from healthy subjects were studied according to the indications of the
      World Health Organization (1992). RESULTS: All the F.A.N.S. used (Cinnoxicam,
      Salicylic Acetyl Acid) had an inhibitory effect on motility, as did L. Carnitine
      at high doses. We thought it interesting to observe if L. Carnitine added to the
      seminal fluid before F.A.N.S. blocked their effects. CONCLUSIONS: The pre
      treatment with L. Carnitine had an "in vitro" buffering effect on F.A.N.S.

PMID- 10958053
TI  - [Gastroesophageal reflux in children].
AB  - Gastroesophageal reflux (GER) is the return of gastric content from stomach to
      esophagus. The above phenomenon takes place for sphincter insufficiency of lower
      esophagus. RGE causes are various. RGE disease must be suspected when a children
      or an infant shows symptoms such as regurgitation and/or after lunch vomit, poor
      weight growth, anorexia, pyrosis, etc. In the last years dietetic and
      pharmacologic therapy have brought an improvement and/or a remission of the GER
      disease.

PMID- 10958054
TI  - Emerging role of protectin (CD59) in humoral immunotherapy of solid malignancies.
AB  - Over the past two decades, complement (C)-activating monoclonal antibodies (mAb),
      directed to specific tumor-associated antigens (TAA), have been extensively
      utilized for passive immunotherapy of solid tumors of different histology.
      However, the clinical outcome of this therapeutic approach has been substantially
      disappointing; antigenic heterogeneity of neoplastic cells and their limited
      accessibility by therapeutic mAb, have been provided as substantial explanations
      for the poor clinical results obtained. Nevertheless, in light of the recent
      advances in the knowledge of the mechanisms regulating C-activity, it begins to
      be evident that membrane and soluble C-inhibitory proteins play a key role in the
      protection of neoplastic cells from C-attack, providing additional insights on
      biological features of transformed cells that may hamper the clinical efficacy of
      humoral immunotherapy. Among C-regulatory proteins investigated, this review will
      focus on protectin (CD59) that represents the main restriction factor of C
      susceptibility of neoplastic cells from solid malignancies. In view of the
      functional role of CD59, we will describe its tissue distribution and biological
      features in malignant neoplasms; major emphasis will be given to cutaneous
      melanoma, in which the C-regulatory role of CD59 has been extensively
      investigated, and clinical approaches of humoral immunotherapy have been
      implemented. According to the available data, the foreseeable strategies to
      improve the therapeutic efficacy of humoral immunotherapy of solid malignancies
      will be discussed.

PMID- 10958056
TI  - [Carcinoma of unknown origin++ with latero-cervical metastasis. Diagnostic
      problems. Retrospective analysis of 110 cases of latero-cervical tumefaction].
AB  - The cervical region, despite to its little extension, is very important by the
      surgical and anatomical point of view. This region, occupied by a lot of organs,
      sometimes is the site of metastasis from carcinomas located in various parts of
      the body. In some cases the origin site of cancer stays unknown. The aim of this
      paper is the retrospective analysis of 110 cases of latero cervical swellings and
      the related problems of differential diagnosis.

PMID- 10958055
TI  - [A 61-year-old woman with abdominal pain and urination disorders].
AB  - The case of a 61 yo diabetic woman presenting with dysuria and lower abdominal
      pain is described. The incomplete resolution of the clinical picture after short
      antibiotic treatment and a strong suspect of autonomic neuropathy oriented to an
      anamnestic reevaluation that evidenced the presence of pneumaturia. The last was
      the key-symptom that guided to diagnostic imaging showing emphysematous cystitis
      while a gastroscopy confirmed the presence of autonomic neuropathy manifested by
      gastroparesis. Emphisematous cystitis is a characteristic infectious complication
      of diabetic patients induced by a persistent incomplete bladder emptying and
      bacterial glucose fermentation. The complete eradication of the infectious agent
      requires a long term antibiotic course and a prompt identification of this
      pathology.

PMID- 10958057
TI  - [Discovery of radioactivity and radium].

PMID- 10958058
TI  - [Consensus interferon: a new weapon in the treatment of chronic hepatitis C].

PMID- 10958060
TI  - Drug resistant tuberculosis in north London.

PMID- 10958059
TI  - [Pseudomembranous colitis caused by Clostridium difficile].

PMID- 10958061
TI  - Age threshold lowered for influenza immunisation and target for coverage
      introduced.

PMID- 10958062
TI  - [75th anniversary of the journal "Surgery"].

PMID- 10958063
TI  - [Analysis of mental functions in patients after coronary bypass surgery].
AB  - The neuropsychological examination was carried out in 18 men (study group), mean
      age 59.7 +/- 6.6 years, before and after aorto-coronary bypass. The
      neuropsychological tests were carried out 2-3 days before operation and 14-16
      days after it. 12 non-operated men with coronary artery disease, mean age 60.0 +/
      6.7 years, were studied as a control group. In control group the
      neuropsychological tests were conducted with a 16-19 day interval. The tests
      examined short-term verbal and visual memory, semantic memory. At statistical
      analysis of the results the mean values and confidential intervals were
      calculated allowing for Student's coefficient. In control group at consecutive
      tests the negative dynamics of the results was not revealed. The comparison of
      the tests results in the study group patients before and after operation revealed
      the a decrease of neuropsychological parameters by 20-40% on the average
      irrespective of material modality. Features of cognitive changes revealed in
      early postoperative period, testifies to diencephalic type of the disorders.

PMID- 10958064
TI  - [Surgery of some diaphragm diseases].
AB  - The authors analyze 127 rare diaphragm diseases. Among them, the rate of true
      diaphragmatic hernias does not exceed 1%. The congenital through diaphragm
      defects were encountered three times more often than false hernias, equally
      frequently on the left and on the right. The majority of the patients (51.97%)
      had hernia of Larrey's fissure. The rate of true hernia (Morgagni's) was 3 times
      less than of false hernia (Larrey's). In Bochdalek's hernia (3.15%) false hernias
      were found three times more often than true hernias. Relaxation of diaphragm was
      found in 40.94% of the patients. Right-sided complete diaphragm's relaxation
      occurred 4 times less often than on the left, partial--10 times more often on the
      right than on the left. Duplication of diaphragm with inserting kapron net,
      velours or teflon between it layers remains the dominant way of surgical
      correction of total relaxation of diaphragm's cupula.

PMID- 10958065
TI  - [Diagnosis and treatment of diaphragm ruptures].
AB  - 72 cases of diaphragm's ruptures in patients with serious combined trauma
      illustrated basic methods of diagnosis in this condition including X-ray,
      ultrasonic methods, computed tomography and thoracoscopy. In 26.3% of the
      patients the diagnosis was made during laparotomy or thoracotomy for massive
      bleeding because of injury of other organs. In the absence of bleeding the
      diagnosis was based on signs of the abdominal organs dislocation into the pleural
      cavity. The differential diagnosis between right-sided coagulated hemothorax and
      diaphragm's right cupula ruptures was the most difficult.

PMID- 10958066
TI  - [Tonicity of autonomic nervous system in patients with complicated gastroduodenal
      ulcer].
AB  - Investigation of autonomic nervous system tonicity has been undertaken in 34
      healthy persons (control group I), in 30 patients with non-complicated duodenal
      ulcer (control group 2), 38 patients with complicated gastroduodenal ulcer (10-
      with perforation, 13--with bleeding, 15--with stenosis) and 32 patients in the
      long-term period. The patients age was from 17 to 75 years. 72 patients were
      males and 28--females. Results of the study showed, that among the patients with
      complicated gastroduodenal ulcer there were eutonics and sympathicotonics, among
      those with non-complicated ulcer disease sympathotonics prevailed. To predict
      occurrence of complicated ulcer, determination of the tone of vegetative nervous
      system in patients with non-complicated ulcer in period between attacks is
      recommended. Identification of phenotype characteristics of vegetative nervous
      system tone allows to predict development of possible postoperative complications
      in patients with gastroduodenal ulcer.

PMID- 10958067
TI  - [Selective proximal vagotomy in combination with drainage operations in duodenal
      ulcers].
AB  - From 1989 to May 1999 selective proximal vagotomy (SPV) was performed in 400
      patients with duodenal ulcer, 190 (47.5%) of them had pyloric stenosis. Various
      drainage operations were performed in 180 patients with stenosis, in 10 patients
      compensated pyloric stenosis was eliminated by excision of the scars around the
      ulcer. Out of 210 patients without pyloric stenosis drainage operations were
      performed in 23 (11.0%) patients with large penetrating duodenal ulcers, which at
      healing could cause stenosis. The best results were received after SPV in
      combination with drainage operations, which save the pyloric mechanism of gastric
      evacuation--transverse duodenojejunostomy (5) and duodenoplasty (15); the results
      after them do not differ from results after SPV without drainage operations.

PMID- 10958068
TI  - [Treatment of patients with foreign bodies in rectum].
AB  - The analysis of treatment results in 112 patients with foreign bodies in the
      rectum, aged from 16 to 80 years, was carried out. 99.1% of the patients were
      men. All the patients were examined and treated in proctology department of the
      Moscow municipal clinical hospital N 67 from 1969 to 1998. The examination was
      made by standard scheme, including rectal touch, rectoromanoscopy, X-ray and
      ultrasonic examinations. In 107 patients the foreign body was removed without
      surgery, 5 patients required laparotomy. When possible it was removed by fingers
      and also with use of forceps. When small foreign bodies could not be reached by
      finger, they were removed through rectoscope. Foreign bodies of big sizes,
      proximal end of which was in the sigmoid colon, were removed under anasthesia
      with the help of the assistant who fixed the foreign body through the abdominal
      wall in the left ileac region. In impossibility of the subject removal by these
      methods and presence of complications (perforation, peritonitis), laparotomy with
      subsequent transanal subject removal without colon section was performed, in case
      of perforation--with wound suturing or colostomy.

PMID- 10958069
TI  - [Use of electrostimulation for treatment of critical lower limb ischemia].
AB  - The analysis of efficiency of bone electrostimulation in the treatment of lower
      limb arteries occlusions was carried out. The method was used in a combination
      with lumbar sympathectomy and revascularising osteotrepanation in 52 patients
      with chronic critical limb ischaemia, in whom reconstructive operation was
      impossible. Short-term good results were achieved in 69.2% of the patients. The
      method allows to accelerate compensation of circulation in ischaemic limb.

PMID- 10958071
TI  - [Rectal foreign body in a child].

PMID- 10958070
TI  - [Surgical interventions in HIV-infected and patients with AIDS].
AB  - 176 patients with HIV-infection and AIDS were examined. 77 of them underwent
      various surgical interventions the most frequent of which were: opening of
      abscess and phlegmons--14 (23%), biopsy of lymphatic nodes--10 (13.1%),
      appendectomy--5 (6.2%), condyloma excision--21 (27.2%), removal of uterus adnexa-
      2 (2.5%), pleural puncture--4 (5.9%), cholecyst- and splenectomy--5 (8.2%).
      Operations for stomach cancer (creation of gastroenteroanastomosis), extrauterine
      pregnancy, brain tumor (drainage of IV ventricle of the brain), penetrating wound
      of cornea were performed less often. 43 patients underwent emergency operations
      without preoperative preparation, 34 patients underwent elective operations. The
      causes of 6 deaths were secondary diseases (Kaposi's sarcoma, purulent processes,
      metastases, pulmonary edema). There were no complications and blood changes in
      postoperative period in infected patients. These patients were discharged in the
      same terms as non-infected patients. In patients with AIDS, especially in
      combination with other infections, fever persisted long after the operation. The
      wound healed by first intention in all the patients, but the sutures were removed
      on day 10-30. Immunologically, a high ratio T-suppressors/T-helpers existed. An
      increase in fibrinolytic activity without high tissues hemorrhage was observed.

PMID- 10958072
TI  - [Cryosurgery of focal liver damages].

PMID- 10958073
TI  - [Selective distal splenorenal shunt in treatment of portal hypertension].

PMID- 10958074
TI  - [Role of scientific school of the academician B.V.Petrovskii in development of
      esophagus surgery in Russia].

PMID- 10958075
TI  - [S.I.Spasokukotskii. 130 years since birthday].

PMID- 10958076
TI  - Effects of diazepam on conditioned place preference induced by morphine or
      amphetamine in the rat.
AB  - RATIONALE: The drug-abuse literature suggests that benzodiazepines may be
      preferentially abused in conjunction with opioids rather than stimulants.
      OBJECTIVE: To investigate possible effects of diazepam on the reinforcing effects
      of morphine and amphetamine. METHODS: The effects of diazepam (0.5, 1 or 2 mg/kg)
      on the formation and expression of conditioned place preferences (CPP) induced by
      morphine sulphate (0.3, 0.8, 2 and 8 mg/kg) or D-amphetamine (0.4, 0.8, 2 or 2.5
      mg/kg) were studied in an unbiased CPP paradigm. The action of diazepam (1 mg/kg)
      on conditioned and unconditioned locomotion induced by morphine (2 mg/kg) or
      amphetamine (2 mg/kg) was assessed. RESULTS: Rats that received conditioning
      injections of morphine in one environment displayed a preference for this
      environment. Pre-testing injections of diazepam did not alter the magnitude of
      this CPP. When diazepam was given with morphine during training, rats displayed a
      CPP for the environment paired with the two drugs. Injections of amphetamine in
      one environment also induced a preference for this environment. However, pre
      testing injections of diazepam blocked the expression of amphetamine-induced CPP,
      and co-injections of diazepam blocked the formation of amphetamine CPP. Diazepam
      itself did not produce a CPP nor did it alter spontaneous place preferences.
      Diazepam equally blocked both morphine and amphetamine unconditioned and
      conditioned locomotor hyperactivity. This indicates that its effects on morphine
      and amphetamine CPP were not due to a differential effect on locomotion.
      CONCLUSIONS: Diazepam interferes with the reinforcing properties of amphetamines
      but not of morphine. The reinforcing effects of morphine and amphetamine are
      pharmacologically dissociable.

PMID- 10958077
TI  - Modulation of intravenous cocaine effects by chronic oral cocaine in humans.
AB  - RATIONALE: Agonist therapies have proven effective for the treatment of substance
      dependence disorders; limited data is available on their feasibility for treating
      cocaine dependence. OBJECTIVES: This laboratory study was designed to test the
      safety and utility of employing an agonist substitution therapy for the treatment
      of cocaine dependence in humans. METHODS: Oral cocaine served as the agonist
      treatment and was administered chronically over a range of doses to volunteers
      with cocaine abuse histories (n=8). Oral capsules were administered daily under
      blind conditions (q.i.d.) during this 5-week inpatient study using a dose-rising
      sequence (0 mg 10 days: 25 mg 3 days, 50 mg 4 days, 100 mg 10 days, 0 mg 7 days).
      During each of these oral dosing periods, an i.v. cocaine challenge (0, 25, and
      50 mg, 1 h apart) was administered at least once. Physiological, subjective and
      pharmacokinetic measures were collected before and after i.v. drug
      administration; additional measures were collected daily. RESULTS: Oral cocaine
      produced no subjective effects or signs of toxicity but produced dose-related
      physiological effects. Significant interactions between oral and i.v. cocaine
      were observed; cocaine (100 mg, p.o.) significantly decreased responses to the 25
      mg but not the 50-mg dose of i.v. cocaine for heart rate, mydriasis, and some
      subjective measures. There was no evidence of significant additive effects,
      although heart rate responses to i.v. cocaine were exaggerated during the final
      wash-out period. CONCLUSIONS: These data indicate that treatment with a cocaine
      "agonist" - in this case oral cocaine - can modestly attenuate the subjective and
      physiological responses to cocaine in humans under conditions that are safely
      tolerated.

PMID- 10958078
TI  - Effects of ethanol at four phases of the menstrual cycle.
AB  - RATIONALE: Ovarian hormones, such as estrogen (E) and progesterone (P), interact
      with neurotransmitters, such as dopamine and gamma-aminobutyric acid, which are
      thought to be important in mediating the effects of ethanol. Therefore, it is
      possible that circulating ovarian hormones influence the acute subjective,
      behavioral, and physiological effects of ethanol, thus indirectly influencing
      ethanol consumption. OBJECTIVES: To examine the relationship between hormone
      levels and consumption of ethanol, this study investigated whether the effects of
      ethanol and the consumption of ethanol vary as a function of menstrual cycle
      phase. METHODS: Sixteen healthy women with normal menstrual cycles ingested
      ethanol at four hormonally distinct phases of the menstrual cycle, namely early
      follicular, late follicular, mid-luteal, and late-luteal. During each session,
      they first sampled three small doses of ethanol (0.2 g/kg each) at half-hourly
      intervals. They completed subjective and behavioral tests before the first dose
      and after each subsequent dose. After consuming the third beverage, the women
      were allowed to choose up to three additional doses of ethanol (0.2 g/kg), one
      every 30 min. RESULTS: Ethanol produced subjective effects typical for this drug
      (such as stimulant-like effects and euphoria), and it impaired eye movements and
      psychomotor performance. However, the effects of ethanol did not vary according
      to menstrual cycle phase, and consumption of ethanol also did not vary across the
      menstrual cycle. CONCLUSIONS: These results suggest that circulating ovarian
      hormones, like E and P, have little effect on either the acute subjective and
      behavioral effects of ethanol, or on ethanol consumption.

PMID- 10958079
TI  - Effects of recent and reference antipsychotic agents at human dopamine D2 and D3
      receptor signaling in Chinese hamster ovary cells.
AB  - RATIONALE: Central dopamine D2 receptor blockade is an essential property of
      antipsychotic agents in the treatment of schizophrenia. However, for certain of
      the newer antipsychotics (e.g., sertindole), the in vitro D2 receptor binding
      affinity does not correlate with in vivo central dopamine antagonism. OBJECTIVE:
      This study aimed to investigate the effect and potency of haloperidol,
      pipamperone, clozapine, risperidone, sertindole, zotepine, olanzapine, and
      quetiapine on signaling pathways of human dopamine D2S and D3 receptors expressed
      in Chinese hamster ovary cells and to relate this to their dopamine antagonist
      potency in vivo. METHODS: Chinese hamster ovary cells, stably expressing high
      levels of hD2S and hD3 receptors were cultured: dopamine-stimulated [35S]
      GTPgammaS binding was investigated in cell membrane preparations, and forskolin
      induced cAMP formation was measured in intact cells. RESULTS: The antipsychotic
      agents inhibited dopamine-stimulated [35S]-GTPgammaS binding mediated by hD2S and
      hD3 receptors with potencies equal to their receptor binding affinities. The
      antipsychotics reversed dopamine inhibition of cAMP formation (equally well
      detectable with both hD2S and hD3 receptors) dose dependently at both receptors.
      Partial agonist effects were not observed with any of the antipsychotics.
      Antagonistic potencies of haloperidol, risperidone, and pipamperone in the cAMP
      test were equal to their receptor binding affinities. Sertindole and olanzapine
      were more than ten times less potent dopamine antagonists in the intact cell
      assay than in the assay using cell membranes; the other compounds showed less
      marked potency differences. CONCLUSIONS: Olanzapine and sertindole were less
      efficacious dopamine antagonists in intact cell assays, possibly due to avid
      uptake in cells. For sertindole, the weak hD2S receptor antagonism in intact
      cells corresponded to a weak in vivo central dopamine antagonism assessed in
      rats. However, for olanzapine, hD2S receptor binding affinity correlated better
      with its in vivo dopamine antagonist potency. Such discrepancies may be further
      explained by relative differences of the compounds in penetrating into the brain.

PMID- 10958080
TI  - Ventral pallidal extracellular fluid levels of dopamine, serotonin, gamma amino
      butyric acid, and glutamate during cocaine self-administration in rats.
AB  - RATIONALE: Dopamine innervation of the nucleus accumbens is thought to have a
      major role in the biological processes underlying cocaine self-administration.
      Recent data suggest that dopamine innervation of the ventral pallidum (VP) may
      also play an important role. OBJECTIVES: This experiment was initiated to assess
      extracellular fluid levels of dopamine (DA), serotonin (5-HT), gamma-aminobutyric
      acid (GABA), and glutamate (Glu) in the VP of rats self-administering cocaine
      using in vivo microdialysis. METHODS: Rats were implanted with intravenous
      jugular catheters and a microdialysis probe guide cannula into the VP and trained
      to self-administer (SA) three different doses of cocaine during each daily
      session. Other rats (yoked rats) were surgically prepared in identical fashion
      and received vehicle infusions during microdialysis sessions when the SA rat to
      whom they were yoked produced cocaine infusions. When stable baselines of self
      administration were obtained, microdialysates were collected during two
      consecutive daily self-administration sessions. Neurotransmitter levels were
      measured using HPLC with electrochemical (DA and 5-HT) or fluorescence detection
      (GABA and Glu). RESULTS: In SA rats, extracellular fluid levels of DA [DA]e and 5
      HT [5-HT]e were elevated throughout the session and levels of Glu [Glu]e showed
      small increases at a few isolated time points during the session. The increases
      in [DA]e and 15-HT]e were dose-dependent. Extracellular fluid levels of GABA
      [GABA]e were unchanged, as were levels of all four neurotransmitters in the yoked
      rats. CONCLUSIONS: These data support a potential role for DA and 5-HT
      innervations of the VP in intravenous cocaine self-administration.

PMID- 10958081
TI  - Component structure of the positive and negative syndrome scale (PANSS) in
      patients with recent-onset schizophrenia and spectrum disorders.
AB  - RATIONALE: Earlier studies have examined the symptom dimensions of the PANSS
      (Positive And Negative Syndrome Scale) in patients with chronic schizophrenia.
      Results have suggested that three to eight component solutions best explain
      underlying symptom dimensions. OBJECTIVES: To examine the component structure of
      the PANSS and the MADRS (Montgomery Asberg Depression Rating Scale) in young
      patients with recent-onset schizophrenia and related disorders and the
      correlations between the components of both instruments. METHODS: Symptomatology
      was measured in 138 patients with recent-onset schizophrenia, by administering
      the PANSS and the MADRS. RESULTS: Principal component analysis of the PANSS
      revealed five components: a positive, negative, depression, agitation-excitement
      and disorganisation component. The MADRS only showed one component. A high
      correlation was found between the depression component of the PANSS and the
      overall score of the MADRS (p=0.87, P<0.001). A moderate correlation was found
      between the PANSS negative component and the overall score of the MADRS (p=0.51,
      P<0.001). CONCLUSIONS: The data suggest a five component structure of the PANSS.
      The depression component of the PANSS seems to be a valid way of assessing
      depression in patients with recent-onset schizophrenia.

PMID- 10958082
TI  - Prolonged perinatal exposure to AZT affects aggressive behaviour of adult CD-1
      mice.
AB  - RATIONALE: AZT is commonly administered to seropositive women and their neonates
      to prevent mother-to-child transmission of HIV. Recently, animal studies
      performed in monkeys and rodents have revealed that pre- and/or perinatal
      exposure to AZT induces age- and sex-dependent behavioural alterations in the
      offspring, possibly resulting from an action of this drug on CNS targets. Long
      term effects of prenatal AZT treatment on social/aggressive behaviour of adult
      male mice have been previously described. Specifically, AZT has been shown to
      induce selective changes in the offensive components of agonistic interactions.
      OBJECTIVE: The aim of the present study was to extend previous findings,
      analysing the long-term effects of a more prolonged AZT exposure on intraspecific
      male mice agonistic behaviour. METHODS: AZT was given orally twice daily to
      pregnant CD- mice. The dosage selected for AZT was 160 mg/kg. Saline solution
      (0.9% NaCl) was used as vehicle. Starting on postnatal day (PND) 60 isolated
      males underwent five 15-min repeated encounters with an opponent of the same age
      and strain isolated for the same amount of time. Furthermore, a locomotor
      activity test (PND 67) and a hot-plate test (52 +/- 0.1 degrees C) (PND 74) were
      performed to assess AZT effects on, respectively, general activity and pain
      sensitivity. RESULTS: AZT perinatal exposure reduced attack behaviour of adult
      mice, while increasing the likelihood of them behaving as subordinates.
      Furthermore, long-term effects of AZT treatment on pain sensitivity were found in
      the hot-plate test, with AZT mice showing higher pain thresholds than controls.
      CONCLUSIONS: Overall, these data indicate that perinatal exposure to drugs such
      as AZT exerts selective effects on the developing CNS, resulting in long-term
      behavioural disturbances. Future studies will need to address the issue of the
      specific mechanisms underlying these effects.

PMID- 10958083
TI  - Alcohol-induced locomotor activation in C57BL/6J, A/J, and AXB/BXA recombinant
      inbred mice: strain distribution patterns and quantitative trait loci analysis.
AB  - RATIONALE: Quantitative trait loci (QTLs) for initial sensitivity to alcohol have
      been identified in a number of mouse strains (e.g. BXD); however, confirmation is
      required. OBJECTIVES: The present paper aimed to characterize the C57BL/6J, A/J,
      and AXB/BXA recombinant inbred (RI) strains of mice for basal and ethanol-induced
      locomotor activation as measured in an open field and to provide provisional
      location of QTLs for these phenotypes. METHODS: A/J and C57BL/6J mice were
      habituated to handling and then randomly assigned to receive one of four alcohol
      doses (0, 0.5, 1.0, 2.0 g/kg). Subsequently, all available strains of the AXB/BXA
      RI were tested with the 2 g/kg dose of ethanol or vehicle control. RESULTS:
      Simple regression and interval mapping were used initially to identify
      significant gene markers associated with ethanol-induced activation (calculated
      as total activity on alcohol day-total activity on saline day). Subsequently,
      composite interval mapping (CIM) was used to increase the accuracy in mapping
      individual loci. Genetic markers on chromosomes 2, 3, 8, 13, 16, 18 and 19 were
      associated with ethanol-induced activation. CONCLUSIONS: Three significant
      markers identified through CIM accounted for 86% of the genetic variance in the
      ethanol-induced activation. QTLs on chromosome 16 (45.6 cM) and 19 (24 cM)
      previously associated with alcohol consumption in the AXB/BXA RI mice were found
      to overlap with QTLs for ethanol-induced activation identified in the present
      study.

PMID- 10958084
TI  - Dopamine D2 receptor occupancy predicts catalepsy and the suppression of
      conditioned avoidance response behavior in rats.
AB  - RATIONALE: Human positron emission tomography (PET) shows that striatal dopamine
      D2 receptor occupancy predicts extrapyramidal side effects (EPS). Patients showed
      a clinical response with > or = 65% D2 occupancy, but EPS only when D2 occupancy
      >78%. Catalepsy and the selective suppression of conditioned avoidance response
      (CAR) are often used as animal models to predict EPS and antipsychotic effect,
      respectively. However, the quantitative relationship between striatal D2
      occupancy and effects in these models is not known. OBJECTIVES: The present study
      intended to investigate the relationship between animal catalepsy, suppression of
      CAR, and D2 receptor blockade using a method of evaluating D2 receptor occupancy
      similar in principle to that used in patients. METHODS: In vivo binding of [11C]
      raclopride and [3H]-raclopride was compared. Doses of cold raclopride were chosen
      to provide a D2 occupancy from 0 to 95%. The relationship between dose/time
      course of catalepsy and D2 occupancy was assessed. Effects of raclopride on
      conditioned avoidance response (CAR) behavior were tested. RESULTS: In vivo
      binding of [11C]-raclopride compared to [3H]-raclopride was virtually the same.
      Using [3H]-raclopride, cold raclopride (0.01-0.2 mg/kg) produced 16-77% D2
      receptor occupancy and no catalepsy. Raclopride (0.5-2 mg/kg) produced 83-95% D2
      occupancy and significant catalepsy. Raclopride (2 mg/kg) produced on average 95%
      and 87% D2 receptor occupancy 1 and 2 h after administration, respectively, and
      maximum catalepsy. D2 occupancy at 4, 8 and 24 h was on average 58%, 46%, and 4%,
      respectively. No catalepsy was observed. Raclopride (0.2 mg/kg), estimated at 70
      75% D2 occupancy, produced suppression of CAR. CONCLUSIONS: In vivo D2 occupancy
      measurements in rats using [3H]-raclopride is analogous to using [11C]-raclopride
      in human PET scanning. Suppression of CAR occurred at a D2 occupancy of around 70
      75%, and catalepsy at D2 occupancy >80%. Results closely resembled human studies
      where 65-70% D2 occupancy was required for antipsychotic response, while > or =
      80% D2 occupancy led to EPS. Brain mechanisms involved in mediation of catalepsy
      in rats and EPS in humans might indeed be similar. Both suppression of CAR in
      rats and antipsychotic response in humans might share an underlying construct,
      i.e. the need for around 70% D2 receptor blockade.

PMID- 10958086
TI  - Predictions and clinical decisions: a fine balance.

PMID- 10958085
TI  - Sex-related differences in the antinociceptive effects of opioids: importance of
      rat genotype, nociceptive stimulus intensity, and efficacy at the mu opioid
      receptor.
AB  - RATIONALE: Recent studies indicate that morphine is more potent as an
      antinociceptive agent in male than female rodents and monkeys. OBJECTIVES: To
      evaluate the influence of sex, nociceptive stimulus intensity and an opioid's
      relative efficacy on opioid-induced antinociception in rat strains (F344 and
      Lewis) that display differential sensitivity to morphine antinociception.
      METHODS: Antinociceptive testing was conducted using a rat warm-water (50-56
      degrees C) tail-withdrawal procedure. Dose-response and time-course
      determinations were performed with various opioids. RESULTS: Across the
      nociceptive stimulus intensities tested, the high-efficacy mu opioids morphine,
      etorphine, and levorphanol were equally effective in males and females, but on
      average 2.5-fold more potent in males. At moderate stimulus intensities, the low
      efficacy mu opioid buprenorphine was approximately 0.4-fold more potent in males,
      and at higher stimulus intensities more potent and effective (greater maximal
      effect) in males. At low stimulus intensities, the low-efficacy mu opioid
      dezocine and the mu/kappa opioid butorphanol were greater than 8.9-fold more
      potent in males, and at moderate stimulus intensities were more potent and
      effective in males. At a low stimulus intensity, the mu/kappa opioid nalbuphine
      was more potent and effective in males. At stimulus intensities in which
      buprenorphine, dezocine, butorphanol, and nalbuphine produced maximal effects in
      males but not females, these opioids antagonized the effects of morphine in
      females. Genotype-related differences were noted as opioids were generally more
      potent in F344 than Lewis males, whereas no consistent differences were observed
      between F344 and Lewis females. CONCLUSIONS: That sex differences in the potency
      and effectiveness of opioids increased with decreases in the opioid's relative
      efficacy and with increases in the nociceptive stimulus intensity suggests that
      the relative efficacy of mu opioids as antinociceptive agents is greater in male
      than female rats.

PMID- 10958087
TI  - Anesthetics and glutamate co-transporters in the central nervous system.

PMID- 10958088
TI  - Predicting difficult intubation: a multivariable analysis.
AB  - PURPOSE: To develop a clinically useful and valid model for predicting difficult
      laryngoscopic tracheal intubation in patients with seemingly normal airways by
      adhering to the principles of multivariable model development. METHODS: This was
      an observational study performed at a tertiary-care teaching hospital.
      Preoperatively, 444 randomly selected patients requiring tracheal intubation for
      elective surgery were assessed. In addition, 27 patients in whom tracheal
      intubation was difficult, but were not assessed preoperatively, were assessed
      postoperatively. One assessor, blinded to the intubation information, collected
      the predictor variables. A reliable definition for difficult intubation was used
      and all attempts were made to eliminate sources of bias. Multivariable modeling
      was performed using logistic regression and the model was validated using the
      bootstrapping technique. RESULTS: Of the 461 patients included in the analysis,
      38 were classified as difficult to intubate. Multivariable analysis identified
      three airway tests that were highly significant for predicting difficult tracheal
      intubation. These were: 1) "mouth opening", 2) "chin protrusion", and 3) "atlanto
      occipital extension". Using these tests, a validated, highly reliable and
      predictive model is produced to determine the probability of difficult intubation
      for patients. At a selected probability cut-off value, the model is 86.8%
      sensitive and 96.0% specific. CONCLUSION: A simple and accurate multivariable
      model, consisting of three airway tests, is produced for predicting difficult
      laryngoscopic tracheal intubation. Additional studies will be required to
      determine the accuracy and feasibility of this model when applied to a large
      sample of new patients by multiple anesthesiologists.

PMID- 10958089
TI  - Comparison of ropivacaine 0.1%-fentanyl and bupivacaine 0.125%-- fentanyl
      infusions for epidural labour analgesia.
AB  - PURPOSE: To compare analgesic efficacies of ropivacaine-fentanyl and bupivacaine
      fentanyl infusions for labour epidural analgesia. METHODS: In this double- blind,
      randomized study 100, term, nulliparous women were enrolled. Lumbar epidural
      analgesia (LEA) was started at cervical dilatation < 5 cm using either
      bupivacaine 0.25% followed by bupivacaine 0.125% + 2 microg x ml(-1) fentanyl
      infusion (n=50) or ropivacaine 0.2% followed by ropivacaine 0.1% + 2 microg x ml(
      1) fentanyl infusion (n=50). Every hour maternal vital signs, visual analog scale
      (VAS) pain score, sensory levels, and motor block (Bromage score) were assessed.
      Data were expressed as mean +/-1 SD and analyzed using Chi -Squared and Mann
      Whitney U tests at <0.05. RESULTS: The onset times were 10.62+/-4.9 and 11.3+/
      4.7 min for the bupivacaine and ropivacaine groups respectively (P = NS). The
      median VAS scores were not different between the groups at any of the evaluation
      periods. However, at least 80% of patients in the ropivacaine group had no
      demonstrable motor block after the first hour compared with only 55% of patients
      given bupivacaine (P =0.01). CONCLUSIONS: Both bupivacaine and ropivacaine
      produce satisfactory labour analgesia. However, ropivacaine infusion is
      associated with less motor block throughout the first stage of labour and at 10
      cm dilatation.

PMID- 10958090
TI  - Unilateral bupivacaine spinal anesthesia for outpatient knee arthroscopy. Italian
      Study Group on Unilateral Spinal Anesthesia.
AB  - PURPOSE: To compare unilateral and conventional bilateral bupivacaine spinal
      block in outpatients undergoing knee arthroscopy. METHODS: One hundred healthy,
      premedicated patients randomly received conventional bilateral (n = 50) or
      unilateral (n = 50) spinal anesthesia with 8 mg hyperbaric bupivacaine 0.5%. A
      lateral decubitus position after spinal injection was maintained in unilateral
      group for 15 min. Times from spinal injection to readiness for surgery, block
      resolution, and home discharge were recorded. RESULTS: Three patients in each
      group were excluded due to failed block. Readiness for surgery required 13 min (5
      - 25 min) with bilateral and 16 min (15 - 30) with unilateral spinal block (P =
      0.0005). Sensory and motor blocks on the operated limb were T9 (T12 - T2) with a
      Bromage score 0/1/2/3: 0/2/0/45 in the unilateral group and T7 (T12 - T1) with
      Bromage score 0/1/2/3: 4/1/6/36 with bilateral block(P = 0.026 and P = 0.016,
      respectively). Vasopressor was required only in five bilateral patients (P =
      0.02). Two segment regression of sensory level and home discharge required 81+/
      25 min and 281+/-83 min with bilateral block, and 99+/-28 min and 264+/-95 min
      with unilateral block (P = 0.002 and P = 0.90, respectively). CONCLUSION: Seeking
      unilateral distribution of spinal anesthesia provided more profound and longer
      lasting block in the operated limb, less cardiovascular effects, and similar home
      discharge compared with bilateral spinal anesthesia, with only a slight delay in
      preparation time.

PMID- 10958092
TI  - Emergency management of deeply comatose children with acute rupture of cerebral
      arteriovenous malformations.
AB  - PURPOSE: To assess the impact of emergency management on mortality and morbidity
      of acute rupture of cerebral arteriovenous malformations resulting in deep coma
      in children, and the factors predicting outcome. METHODS: Retrospective chart
      review of 20 children with a Glasgow Coma Scale < or = 8 with acute hemorrhagic
      stroke from a cerebral arteriovenous malformation rupture was conducted. Protocol
      included: early resuscitation with tracheal intubation and ventilation after
      induction of anesthesia with sufentanil, and benzodiazepine, and mannitol 20% or
      hypertonic saline 7.5% infusion for life-threatening brain herniation.
      Radiological exploration was limited to contrast-enhanced CT scan preceding
      immediate surgical decompression. Postoperatively, children were deeply sedated
      and intracranial pressure monitoring allowed titration with osmotherapy,
      vasopressors, hyperventilation or barbiturate coma to control cerebral perfusion
      pressure. Analysis used stratification of the type of hemorrhage (supra or infra
      tentorial), location (intraparenchymal and subarachnoid, intraparenchymal and
      intraventricular or intraventricular alone) and relationship between
      presentation, evolution with resuscitation, type of cerebral lesion, and outcome.
      RESULTS: Patients had a severe initial presentation (median Glasgow Coma Scale
      five), eight had unilateral and eight bilateral third nerve palsy. Compressive
      hematoma in supratentorial localisation represented 75% of the cases. Global
      mortality was 40%. Persistence of mydriasis after resuscitation increased
      mortality to 75%. Massive intraventricular flooding was associated with increased
      mortality. Good functional outcome was achieved in survivors. CONCLUSION: Acute
      rupture of an AVM can result in rapidly progressing coma. Emergency management
      with early resuscitation, minimal radiological exploration before rapid surgical
      decompression results in a mortality rate of 40%, but a good functional outcome
      can be expected in the survivors.

PMID- 10958091
TI  - Premedication with low dose oral clonidine does not enhance postoperative
      analgesia of intrathecal morphine.
AB  - PURPOSE: A number of studies have demonstrated that perioperative intravenous,
      intrathecal, and epidural clonidine enhance postoperative analgesia. The results
      of previous studies on the usefulness of oral clonidine on enhancing
      postoperative analgesia have been mixed. The effect of a single preoperative dose
      of oral clonidine on postoperative analgesia was assessed in this study. METHODS:
      Forty-three male patients undergoing radical prostectomy were randomized to
      receive either 3 microg x kg(-1) clonidine or placebo po 90 min prior to surgery.
      All patients received isobaric 15 mg bupivacaine and intrathecal 5 microg x kg
      morphine, followed by a standardized general anesthetic, consisting of
      thiopental, sufentanil, rocuronium, isoflurane, oxygen and air. Postoperatively,
      PCA morphine use and visual analogue pain scores were recorded for the first 48
      hr. The incidence and severity of side effects such as sedation, nausea, and
      pruritus were assessed, as well as patient satisfaction. Usage of PCA morphine
      was compared. RESULTS: There was no difference in total morphine requirements
      between the placebo and oral clonidine groups, nor in six hourly morphine usage
      (P = 0.96). Second, there was no difference in visual analogue pain scores, or
      the incidence of side effects. Patient satisfaction was high in both groups and
      again, no differences between groups was noted. CONCLUSIONS: Oral clonidine 3
      microg x kg(-1) as a premedication does not prolong the effect of intrathecal
      morphine: there was no difference in PCA morphine requirements (P = 0.96).
      Clonidine did not effect the incidence or severity of nausea or pruritus.

PMID- 10958093
TI  - Reduction of cerebral hyperemia with anti-hypertensive medication after
      electroconvulsive therapy.
AB  - PURPOSE: Several different anti-hypertensive regimens have been introduced for
      the prevention of systemic hyperdynamic responses after electrically induced
      seizures. In the present study, the effects of anti-hypertensive medications on
      cerebral circulation were studied. METHODS: Systemic blood pressure was
      controlled by several anti-hypertensive medications, nicardipine, prostaglandin
      EI, alprenolol and nitroglycerin, in 30 patients (150 electroconvulsive therapy
      trials). Changes in cerebral blood flow velocity were measured by transcranial
      Doppler sonography of the right middle cerebral artery from the start of
      anesthesia to 10 min after the electrical shock. RESULTS: Administration of a
      Ca2+ antagonist, nicardipine, or prostaglandin EI did not alter the augmented
      cerebral blood flow velocity after the seizure. However, a beta-adrenergic
      blocking agent, alprenolol (P<0.05) or nitroglycerin (P<0.01) partially inhibited
      the increase in cerebral blood flow velocity. Maximal blood flow velocity was
      133% larger than the pre-anesthesia value in the control group, 109% in the
      nicardipine group, 113% in the prostaglandin EI group, 72% in the alprenolol
      group, and 45% in the nitroglycerin group, respectively. The increase in cerebral
      blood flow velocity after electrically induced seizure was independent of
      systemic blood pressure. Internal jugular venous saturation (SjO2) was increased,
      and difference in arterial and venous concentrations of lactate was not altered
      in all groups. CONCLUSIONS: Cerebral hemodynamics is altered by ECT, even when
      systemic hemodynamics are stabilized by antihypertensive medication. Although the
      effects of antihypertensive medicine on cerebral hemodynamics are variable,
      systemic blood pressure control by these agents does not induce cerebral ischemia
      after ECT.

PMID- 10958094
TI  - Bronchial cuff pressure change caused by left-sided double-lumen endobronchial
      tube displacement.
AB  - PURPOSE: The bronchial cuff pressures (BCPs) of left-sided double-lumen
      endobronchial tubes (DLTs) manufactured by Rusch and Mallinckrodt were measured
      in 80 patients when the tubes were withdrawn to compare the effect of tube design
      on BCP change. METHODS: During general anesthesia with muscle relaxation, the
      cephalad surface of the endobronchial cuff was positioned either 2.5 cm distal to
      the carina (Rusch Group R-I; n = 20 and Mallinckrodt Group B-I; n = 20) or just
      below the carina (Rusch Group R- II; n = 20 and Mallinckrodt Group B- II; n = 20)
      and the cuff was inflated to 35 cm H2O. The tube was then withdrawn in 0.5-cm
      steps until the cuff was 2.0 cm proximal to the carina, the position just before
      the capnogram or pressure-volume loop of tracheal lumen changed. The BCP at each
      step was measured. The rate of decrease in BCP was defined as the decrease of BCP
      divided by the length of displacement of DLT. RESULTS: The rates of decrease from
      the +2.5 cm position to the end point in Group B-I (7.7+/-0.8 cm H2O x cm(-1) and
      those from the most proximal acceptable position to the end point in Group B-II
      (19.5+/-4.8 cm H2O x cm(-1) were greater than those in Group R-I (6.9+/-0.9 cm
      H2O x cm(-1) (P<0.01) and in Group R-II (12.4+/-3.1 cm H2O x cm(-1)) (P<0.01),
      respectively. CONCLUSION: The BCP decreased in both of the Mallinckrodt and Rusch
      DLTs, and the rates of decrease of the former were greater than those of the
      latter.

PMID- 10958096
TI  - Acute changes in bladder volume produce minimal cardio-respiratory responses in
      lightly anesthetised humans.
AB  - PURPOSE: To examine whether changes in bladder volume elicit reflex
      cardiovascular and respiratory responses in humans under general anesthesia with
      sevoflurane and nitrous oxide. METHODS: Fourteen patients free of autonomic
      disorders were anesthetized with sevoflurane 0.5% and nitrous oxide 60% in oxygen
      that were approximately equivalent to 0.9 MAC. Warmed saline (6 ml x kg(-1), 37
      degrees C) was instilled into the pre-emptied urinary bladder, and then the
      bladder was kept distended for five minutes. Following the distension, the
      instilled saline was drained to the pre-instilled volume of the bladder Arterial
      blood pressure, respiratory flow, and intra-vesicle pressure were continuously
      measured, and mean arterial pressure, pulse rate, respiratory rate, tidal volume,
      and minute ventilation were estimated offline from these signals. RESULTS:
      Bladder emptying produced small decreases in mean blood pressure (from 83.4+/-4.3
      to 80.0+/-4.4 mm Hg, mean +/- SE, P = 0.017) and pulse rate (from 72.2+/-2.9 to
      69.4+/-2.7 bpm, mean +/- SEM, P = 0.004). Only minimal respiratory reflexes were
      invoked by the bladder volume changes. CONCLUSION: In lightly anesthetized
      humans, the acute changes in bladder volume produce only mild cardiovascular and
      respiratory responses.

PMID- 10958095
TI  - Dimenhydrinate and metoclopramide alone or in combination for prophylaxis of
      PONV.
AB  - PURPOSE: Dimenhydrinate and metoclopramide are inexpensive antiemetic drugs.
      Metoclopramide, especially, has been studied extensively in the past, but there
      are no studies on the combination of both drugs for prevention of postoperative
      nausea and vomiting (PONV). METHODS: One hundred and sixty male inpatients
      undergoing endonasal surgery were randomized to receive one of four antiemetic
      regimens in a double-blind manner: placebo, 1 mg x kg(-1) dimenhydrinate, 0.3 mg
      x kg(-1) metoclopramide, or the combination of both drugs was administered after
      induction of anesthesia. Patients received a second dose of these drugs six hours
      after the first administration to mitigate their short half-life. Standardized
      general anesthesia included benzodiazepine premedication, propofol, desflurane in
      N2O/O2 vecuronium, and a continuous infusion of remifentanil. Postoperative
      analgesia and antiemetic rescue medication were standardized. Episodes of
      vomiting, retching, nausea, and the need for additional antiemetics were recorded
      for 24 hr. The incidences of PONV were analyzed with Fisher's Exact test and the
      severity of PONV (rated by a standardized scoring algorithm) with the Jonckheere
      Terpestra-test. RESULTS: The incidence of patients free from PONV was 62.5% in
      the placebo-group and increased to 72.5% in the metoclopramide-group (P = 0.54),
      75.0% in the dimenhydrinate-group (P = 0.34), and 85.0% in the combination- group
      (P = 0.025). In the latter group, the severity of PONV was reduced compared with
      placebo treatment (P = 0.017; Jonckheere-Terpestra-test). CONCLUSION:
      Dimenhydrinate and metoclopramide were ineffective in reducing the incidence and
      the severity of PONV. Their combination reduced the incidence of PONV compared
      with placebo.

PMID- 10958097
TI  - Management of prolonged QT interval during a massive transfusion: calcium,
      magnesium or both?
AB  - PURPOSE: This case report describes the intra-operative management of a prolonged
      QT interval in the setting of massive transfusion. CLINICAL FEATURES: A
      previously healthy, 45-yr-old man presented for repair of a class IV thoraco
      abdominal aneurysm. The initial stages of the operation were relatively
      uneventful, with the exception of an estimated blood loss of 5.0 L. At this point
      the patient's QT interval became markedly prolonged, and subsequently narrowed in
      response to supplemental calcium and magnesium. A blood sample taken just before
      QT prolongation revealed an ionized calcium of 0.98 mmol x L(-1) and an ionized
      magnesium of 0.37 mmol x L(-1), indicating, that low magnesium may have
      contributed to the QT interval prolongation. CONCLUSION: This case illustrates
      the importance of following both ionized calcium and magnesium in the setting of
      a massive transfusion.

PMID- 10958098
TI  - Foreign body aspiration following unconventional use of a metered dose inhaler.
AB  - PURPOSE: Aspiration of a foreign body may be life-threatening. This report
      describes laryngeal obstruction after inhalation of a piece of a Turbuhaler which
      resulted from a patient tampering with the device. CLINICAL FEATURES: A 27-yr-old
      man disassembled a Turbuhaler and inadvertently aspirated a plastic dispensing
      medication disc (22 mm diameter) while attempting to inhale the remnant
      terbutaline sulfate which accumulated on it. Although the patient was hoarse, he
      was not in acute respiratory distress. X-ray revealed the disc lodged in the
      larynx below the vocal cords. The patient was immediately transferred to an
      operating theatre, and a drying agent (glycopyrrolate), judicious sedation
      (midazolam and fentanyl) and O2 were administered. The airway was anesthetized
      with lidocaine 4% delivered using high-flow O2 through an atomizer. Direct
      laryngoscopy revealed a partially obstructed view of the disc lodged distal to
      the vocal cords which was inaccessible for retrieval. Loss of consciousness was
      subsequently induced by spontaneous mask ventilation with sevoflurane (in O2).
      The airway was visualized using a suspension laryngoscope and the foreign body
      was removed with grasping forceps. The patient was awakened, transferred to the
      ICU and given 4 mg decadron i.v. every eight hours (two doses). Laryngoscopy
      prior to discharge indicated good mobility of the vocal cords and normal glottic
      structure. CONCLUSION: Aspiration of a foreign body is a potentially life
      threatening situation requiring coordination between anesthesiologist, surgeon,
      and nursing staff. Anesthetic goals include avoidance of upper airway obstruction
      and maintenance of adequate ventilation while the foreign body is retrieved.
      Provisions must be made for tracheostomy if these goals cannot be realized.

PMID- 10958099
TI  - Midazolam and ketamine inhibit glutamate release via a cloned human brain
      glutamate transporter.
AB  - PURPOSE: In cerebral ischemia/anoxia, the glutamate transporter runs in reverse
      and releases glutamate into the extracellular space, causing irreversible
      neuronal damage. Intravenous anesthetics attenuate overall glutamate release and
      prevent neuronal injury during anoxia/ischemia, but their effect on the glutamate
      transporter is variable. METHODS: A human glial glutamate transporter (hGLT-I)
      cDNA was isolated by screening a human cerebral cortical library. Cloned cDNA was
      transfected in Chinese hamster ovary cells. The effect of the intravenous
      anesthetics midazolam (0.3 to 30 microM), ketamine (10 to 100 microM), thiopental
      (30 to 300 microM), and propofol (3 to 30 microM) on reversed uptake of L
      glutamate via hGLT-I was examined by whole-cell patch-clamp. RESULTS: Midazolam
      at a concentration 3 microM reduced outward currents arising from reversed L
      glutamate uptake via hGLT-I in a concentration-dependent manner. While, ketamine
      at 100 microM attenuated the same outward currents, to 53.3+/-11.4% of those seen
      in controls without anesthetics (P<0.05, n=5). In contrast, neither thiopental
      nor propofol showed effects on outward currents mediated by reversed operation of
      hGLT-I. CONCLUSIONS: These results suggest that midazolam and ketamine, but not
      thiopental and propofol, have a capacity to inhibit glutamate release via GLT- I
      directly.

PMID- 10958100
TI  - Heart rate variability during massive hemorrhage and progressive hemorrhagic
      shock in dogs.
AB  - PURPOSE: To investigate the sequential changes in heart rate (HR), autonomic
      nervous activity presented by the spectral analysis of heart rate variability
      (HRV), hemodynamics and metabolism during massive hemorrhage and progressive
      hemorrhagic shock in dogs. METHODS: Twelve dogs were subjected to acute massive
      hemorrhage until mean arterial pressure (MAP) reached 50 mm Hg. Then bleeding was
      stopped and they were allowed to reach a plateau phase. They were divided, post
      hoc, into bradycardic or tachycardic groups according to their HR response to the
      acute massive hemorrhage. After reaching a plateau phase, the dogs were further
      bled to keep their MAP around 50 mmHg (progressive hemorrhagic shock). Their
      heart rate power spectra were quantified into low-frequency (LF) (0.04-0.15 Hz)
      and high-frequency (HF) (0.15-0.4 Hz) components. RESULTS: In the bradycardic
      group, both LF and HF increased after massive hemorrhage, but during progressive
      hemorrhagic shock these components decreased while HR increased. In the
      tachycardic group, LF increased after massive hemorrhage, but during progressive
      hemorrhagic shock LF decreased with continuous suppression of HF CONCLUSION:
      Massive hemorrhage caused two types of HR response: bradycardia and tachycardia.
      The HRV profile showed differential autonomic characteristics, and could be a
      valuable tool in assessing various degrees of hemorrhagic shock.

PMID- 10958101
TI  - Wound closure tramadol administration has a short-lived analgesic effect.
AB  - PURPOSE: To evaluate the effects of tramadol administration at wound closure on
      postoperative pain and analgesic requirements in patients undergoing laparoscopic
      cholecystectomy. METHODS: In a prospective, randomized, double-blind study 80
      patients were allocated into two groups (n = 40 in each) to receive either 200 mg
      tramadol or placebo i.v. at the time of wound closure. Postoperatively, all
      patients received tramadol from a patient-controlled analgesia (PCA) device.
      Pain, analgesic consumption, vital signs and side effects were recorded
      postoperatively for 24 hr. RESULTS: Administration of 200 mg tramadol at the time
      of wound closure was associated with a short-lived (60 min) reduction in pain
      scores and PCA consumption compared with placebo. Although the time to first
      request for analgesia after surgery was longer in patients who received tramadol
      at wound closure, there was no difference between the two groups with respect to
      pain scores or to the requirements of postoperative analgesia over the next 23
      hr. The cumulative PCA consumption of tramadol in 24 hr was 139.4+/-108 and
      102.4+/-106 mg in the placebo and tramadol groups, respectively (P = 0.06).
      CONCLUSIONS: Wound closure administration of 200 mg tramadol had a short-lived
      (60 min) analgesic effect but did not affect the long-term pain scores or
      analgesic requirements after laparoscopic cholecystectomy.

PMID- 10958103
TI  - Dr. Stuart L. Vandewater (b. 1924).

PMID- 10958104
TI  - CD-ROM review: the evolution of the anesthesia machine.

PMID- 10958102
TI  - Effect of xenon on diaphragmatic contractility in dogs.
AB  - PURPOSE: This study was undertaken to examine the effect of xenon on
      diaphragmatic contractility in pentobarbitone- anesthetized, mechanically
      ventilated dogs. METHODS: Twenty-one dogs were randomly allocated to three groups
      (n=7 of each): Group I received oxygen 100%; Group II received xenon 30% in
      oxygen; Group III received xenon 60% in oxygen. Diaphragmatic contractility was
      assessed by measuring transdiaphragmatic pressure (Pdi) generated during
      supramaximal stimulation of phrenic nerves at the neck at low-frequency (20-Hz)
      and high-frequency (100-Hz) stimulation, after maintaining 60 min of stable
      condition. RESULTS: With inhalation of xenon at two different concentration (30%
      and 60%), no changes were observed in Pdi at either concentration. There was no
      difference in Pdi among the three groups. CONCLUSION: Increasing the
      concentration of xenon to 60% has no effect on diaphragmatic contractility in
      dogs. This suggests that xenon may be used safely as an anesthetic with respect
      to respiratory muscle function.

PMID- 10958105
TI  - Embedded computers in the operating room and in the intensive care unit.

PMID- 10958106
TI  - Arrhythmia and Charcot-Marie-Tooth disease during anesthesia.

PMID- 10958107
TI  - [Malfunction of an artificial pacemaker secondary to an accidental breaking of
      the case].

PMID- 10958108
TI  - Sedation for MRI scans in children.

PMID- 10958109
TI  - Effects of two acute stressors on the anxiolytic efficacy of chlordiazepoxide.
AB  - RATIONALE: Limited published data show that drug efficacy can be influenced by
      stressors. Thus, drug testing in stressed animals may unravel important variables
      determining drug effects. OBJECTIVES: The experiments tested the anxiolytic
      efficacy of the benzodiazepine chlordiazepoxide under conditions of acute stress.
      METHODS: Previously group-housed rats were injected with 0, 3, and 10 mg/kg
      chlordiazepoxide, thereafter being exposed to two types of stress: novelty
      (transfer to an individual cage) and social defeat. Controls were group-housed
      animals. Anxiety was assessed on the plus maze. RESULTS: Speed of locomotion was
      increased by chlordiazepoxide in both stressed groups but not in controls.
      Chlordiazepoxide exerted a marked reduction in anxiety in controls and defeated
      rats but not in novelty exposed animals. The effects of novelty exposure were
      considerably weaker when drug testing was performed 24 h later. CONCLUSIONS:
      Stress exposure had an impact on the behavioral effects of chlordiazepoxide.
      Changes in locomotor activity induced by the drug appear to depend on the
      presence of a stressor, while anxiolytic efficacy appears to depend on the type
      of the stressor. Since it has been shown that drug efficacy changes in a variety
      of behavioral situations and drug classes, it is suggested that experimental
      background is an important variable in determining behavioral effects of drugs.

PMID- 10958110
TI  - Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after
      chronic treatment with different subclasses of antidepressants in the rat.
AB  - There is a latency period of several weeks before the onset of clinical effect of
      antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive
      neuronal changes are not known. To elucidate the involvement of changes in gene
      expression of candidate transcription factors, we treated rats for 21 days with
      buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used
      to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and
      GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and
      the cerebral cortex after all drug treatments, especially after moclobemide
      treatment (77-122% increase); with the exception of buspirone. MR mRNA expression
      was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants,
      while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly
      in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the
      hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by
      moclobemide treatment. There are selective effects of antidepressant drugs on
      specific transcription factors. These may be important for adaptive neuronal and
      neuroendocrine changes after antidepressant treatment including HPA axis negative
      feedback regulation.

PMID- 10958111
TI  - Conditioned locomotor stimulant effects of cocaine in rats do not result from
      interference with habituation.
AB  - RATIONALE: Classical conditioning has been proposed to account for the
      hyperactivity observed in drug-free rats when placed in an environment previously
      paired with cocaine administration. However, an alternative explanation is that
      hyperactivity results from an inability of rats to habituate to the environment
      under the influence of cocaine. OBJECTIVES: In this study, preconditioning
      exposure to the test environment was increased from one session (standard
      procedure) to seven (modified procedure) to test the "antihabituation"
      hypothesis. METHODS: After preconditioning exposure, six conditioning sessions
      took place over a 10-day to 13-day period. Paired rats received 10 mg/kg cocaine
      i.p. prior to activity sessions and saline i.p. upon return to the colony room.
      Unpaired rats received saline prior to and cocaine after activity sessions. Time
      off rats were withheld from the activity boxes, but were subject to all other
      procedures during conditioning. On the test day, all rats received saline prior
      to activity sessions. RESULTS: In the standard procedure, paired rats exhibited
      significantly greater activity than unpaired rats on the test day, consistent
      with previous reports. In the modified procedure, mean activity (all rats)
      decreased between the first and last preconditioning sessions. Still, the paired
      group exhibited greater activity than the unpaired group on the test day,
      suggesting that a conditioned stimulant effect developed in habituated rats.
      Activity in the time-off group did not significantly differ from the unpaired
      group demonstrating the habituation had not dissipated over this time period.
      CONCLUSIONS: These results support the conclusion that hyperactivity observed on
      the test day was not a result of antihabituation effects of cocaine.

PMID- 10958112
TI  - Cognitive performance amongst recreational users of "ecstasy".
AB  - RATIONALE: Previous work has suggested that memory impairments have been
      associated with the recreational use of "ecstasy". This previous work, however,
      has not taken into consideration the additional use of cannabis amongst those
      examined. Cannabis use has also been associated with memory impairment. There is
      therefore a clear need to explore the impact of both of these illicit substances
      upon memory ability. OBJECTIVES: To determine whether recreational use of ecstasy
      impairs memory and attentional ability and to explore the impact of the
      concomitant use of cannabis upon these cognitive functions. In addition, an
      exploration of subjective accounts of cognitive ability was undertaken to
      determine whether objective impairments were perceived by users in everyday
      functioning. METHODS: Cognitive functioning was examined in three groups of young
      people: 15 regular users of ecstasy; 15 regular users of cannabis who had never
      taken ecstasy and 15 control subjects who had never taken any illicit substances.
      The Weschler Memory Scale (revised) and a computerised reaction time task were
      administered on a day when the subjects claimed to be drug free. In addition,
      subjects completed a biographical questionnaire and the Cognitive Failures
      Questionnaire (CFQ) in order to assess subjective accounts of cognitive slips.
      RESULTS: Performance was similar across all three groups for measures of visual
      reaction time, auditory reaction time, complex reaction time, visual memory and
      attention and concentration. Significant impairment was found on measures of
      verbal memory in both cannabis users and ecstasy users. A significant impairment
      in performance was found on measures of delayed memory for the ecstasy users
      compared to both the cannabis group and the control group. Despite these
      findings, no differences in subjective ratings of cognitive failures were found
      between the groups. CONCLUSIONS: The present study provides additional evidence
      for longterm neuropsychological sequelae associated with the use of ecstasy,
      particularly with regard to delayed memory ability.

PMID- 10958113
TI  - Cannabinoid receptors and reward in the rat: a conditioned place preference
      study.
AB  - RATIONALE: We wished to investigate further the hypothesis of an endogenous
      cannabinoid 'aversive counter-rewarding system, as the rewarding properties of
      cannabinoids using standard procedures remain ambiguous. OBJECTIVES: The purpose
      of this study was to confirm the behavioural effects of a highly potent synthetic
      cannabinoid agonist (HU210) and the selective cannabinoid antagonist SR 141716A
      using conditioned place preference (CPP). METHODS: HU210 (20, 60 and 100 microg
      kg(-1), SR141716A (0.25, 0.5, 2 and 3 mg kg(-1)), cocaine (15 mg kg(-1) and
      delta9-THC (1.5 mg kg(-1)) were given to male Lister hooded rats using an
      unbiased CPP design. RESULTS: SR141716A and cocaine produced place preference at
      all doses tested, whereas HU210 and delta9-THC produced aversion as expressed by
      time spent in the drug-paired compartment of the CPP apparatus. CONCLUSIONS: The
      aversive effects of cannabinoid agonists and the rewarding effect of the
      cannabinoid antagonist are suggestive of a cannabinergic tone in the rat brain.
      Further research is needed to determine the precise relationship of that tone
      with the reward pathways of the brain.

PMID- 10958115
TI  - PHNO, a selective dopamine D2 receptor agonist, does not reduce prepulse
      inhibition of the startle reflex in rats.
AB  - RATIONALE: Dopamine agonists nonselective for dopamine receptor subtypes, such as
      apomorphine, reduce prepulse inhibition of the startle reflex. It has been
      suggested that either D2 or D3 dopamine receptors mediate this action of
      apomorphine. OBJECTIVE: The present study investigated whether a selective D2
      agonist with relatively low affinity for D3 receptors can reduce prepulse
      inhibition. METHODS: Rats (n=48) were treated with vehicle or one of three doses
      ( 15, 30 or 60 microg/kg, s.c.) of the specific dopamine D2 receptor agonist (+)
      4-propyl-9-hydroxynaphthoxazine (PHNO) for 11 days. On days 1, 6 and 11 of
      treatment, the rats (n=12 in each group) were tested for their acoustic startle
      reflexes (105-dB, 40-ms white noise) and for prepulse inhibition (5-kHz tone, 5
      dB above a 65 dB background white noise). Prepulses were presented with a range
      of stimulus onset asynchronies (SOAs: 5-160 ms) or lead times between the onset
      of the prepulse and the onset of the startle stimulus. In a second experiment,
      two groups of rats (n=10 in each group) were tested in a similar manner after
      vehicle or apomorphine (0.8 mg/kg, s.c.) to verify the sensitivity of the present
      procedure to agonist-induced reductions in prepulse inhibition. RESULTS: At doses
      that increased motor activity, PHNO increased prepulse inhibition at SOAs less
      than 80 ms and had no effect on prepulse inhibition at SOAs of 80 ms or above.
      However, all doses decreased startle amplitudes on trials in which only the
      startle-eliciting stimulus was presented. Apomorphine reduced prepulse inhibition
      under the same conditions. CONCLUSIONS: These findings with PHNO are in contrast
      to the less-specific D2 agonist, quinpirole, which has been reported to decrease
      prepulse inhibition. It is concluded that activation of D2 dopamine receptors
      alone is not sufficient to attenuate prepulse inhibition of the startle reflex.

PMID- 10958114
TI  - The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable
      shock in the rat.
AB  - RATIONALE AND OBJECTIVES: The ability of progesterone (P4) and its neurosteroid
      metabolite, 3alpha-OH-5beta-pregnan-20-one (pregnanolone) in protecting against
      the anxiogenic-like effect of inescapable shock (IS) in male rats was examined,
      as these steroids exert anxiolytic, anticonvulsant, and ataxic effects similar to
      the benzodiazepines (BZ), drugs shown to prevent IS-induced anxiogenesis.
      METHODS: Adult male rats were injected with pregnanolone (8 mg/kg, SC), P4 (4
      mg/rat) or its appropriate vehicle before exposure to IS. Twenty-four hours
      later, animals were injected with the steroid or its vehicle and then tested in
      the elevated plus-maze. In a control experiment, animals were injected with
      chlordiazepoxide (CDP, 15 mg/kg, IP) or vehicle before IS, and tested in the plus
      maze 24 h later. RESULTS: Whereas CDP or pregnanolone before IS resulted in the
      loss of the anxiogenic-like response seen 24 h after IS, P4 before IS did not
      protect against the anxiogenic-like effect of IS. The acute anxiolytic-like
      effect of pregnanolone and P4 was lost in animals that were injected with vehicle
      before the IS, but was observed in animals that were injected with the steroids
      before IS. Moreover, P4 injection in non-shocked animals was associated with an
      anxiogenic-like response observed 24 h after steroid administration. CONCLUSION:
      The protection against the effect of IS afforded by a GABAergic neurosteroid is
      comparable to that observed with BZs, and thus provides further evidence of an
      allosteric relationship between the neurosteroid and BZ binding site on the
      GABA(A) receptor complex.

PMID- 10958117
TI  - Leftward shift in the acquisition of cocaine self-administration in isolation
      reared rats: relationship to extracellular levels of dopamine, serotonin and
      glutamate in the nucleus accumbens and amygdala-striatal FOS expression.
AB  - RATIONALE: Dopamine dysfunction in the nucleus accumbens is thought to underlie
      the altered propensity of isolation-reared rats to self-administer psychomotor
      stimulants. OBJECTIVE: To identify specific changes in monoamine and glutamate
      function in the nucleus accumbens and c-fos induction in the amygdala and
      striatum which may be correlated with altered cocaine self-administration in
      isolates. METHODS: In three separate studies, group-reared and isolation-reared
      rats were trained to self-administer cocaine (0.083. 0.25 or 1.5 mg/kg per IV
      infusion; FR1), intracerebral microdialysis was used to measure cocaine-induced
      changes in extracellular levels of dopamine, serotonin and glutamate in the
      nucleus accumbens and the expression of the immediate-early gene c-fos was
      quantified using quantitative immunocytochemistry of its protein product Fos in
      several amygdala and striatal brain regions following cocaine administration.
      RESULTS: Isolation-reared rats showed an enhanced sensitivity to self-administer
      the lowest dose of cocaine but showed retarded acquisition at the highest dose.
      Isolation rearing produced no effect on basal levels of dopamine, serotonin or
      glutamate in the nucleus accumbens but potentiated the increase in dopamine
      efflux, though not serotonin efflux, induced by cocaine. Cocaine increased FOS
      expression in most amygdala and striatal brain regions examined that were
      relatively greater in isolation-reared rats in core and shell regions of the
      nucleus accumbens, medial and lateral regions of the dorsal striatum as well as
      the central nucleus of the amygdala. CONCLUSION: These data are consistent with
      the hypothesis that isolation rearing produces enduring changes in the
      sensitivity of dopamine-mediated functions in amygdala-striatal circuitry that
      may be directly related to the altered reinforcing properties of cocaine and
      other psychomotor stimulants.

PMID- 10958118
TI  - Activation of peripheral mitochondrial benzodiazepine receptors in the
      hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like
      effects in the rat.
AB  - RATIONALE AND OBJECTIVES: Stimulation of the mitochondrial benzodiazepine
      receptor (MBR) in the brain activates the synthesis of neurosteroids that can act
      as positive modulators of the GABA(A) receptor complex. Allopregnanolone is a
      potent anxiolytic, anticonvulsant, sedative and hypnotic GABAergic neurosteroid.
      The anxiolytic-like effects of FGIN 1-27, an MBR agonist, were determined after
      microinjection into the dorsal hippocampus. METHODS: Behavior in the elevated
      plus-maze was assessed in adult male rats after bilateral injections of 0, 1.25,
      2.5, or 5 microg FGIN 1-27. The behavioral effects of FGIN 1-27 were also
      determined in animals receiving intrahippocampal co-administration of 20 ng
      picrotoxin, 5 microg flumazenil, or 200 ng PK 11195. The effects of FGIN 1-27 on
      behavior in the elevated plus-maze and shock-probe burying test were measured in
      animals pretreated systemically with 10 mg/kg 4-MA, a 5alpha-reductase inhibitor.
      Hippocampal and blood plasma levels of allopregnanolone were measured in separate
      groups of animals pretreated with 4-MA and receiving an intrahippocampal
      injection of FGIN 1-27. RESULTS: Intrahippocampal injections of FGIN 1-27
      produced anxiolytic-like effects in the plus-maze and in the shock-probe burying
      test. Hippocampal and blood levels of allopregnanolone were also increased by
      FGIN 1-27. The anxiolytic-like effects of FGIN 1-27 were attenuated by PK 11195
      and were blocked by picrotoxin and 4-MA pretreatment, but remained unaffected by
      flumazenil pretreatment. The neurosteroidogenic effect of FGIN 1-27 was also
      eliminated by 4-MA. CONCLUSION: Activation of the MBR in the hippocampus leads to
      the synthesis of allopregnanolone, an anxiolytic neurosteroid that potentiates
      GABA(A) receptor function.

PMID- 10958116
TI  - Modulation of opioidergic system on mecamylamine-precipitated nicotine-withdrawal
      aversion in rats.
AB  - RATIONALE: Several lines of evidence indicate that central opioid systems may be
      involved in the behavioral effects of nicotine. We previously reported that
      mecamylamine-precipitated nicotine-withdrawal aversion can be evaluated using the
      conditioned place preference paradigm. OBJECTIVES: In the present study,
      modulation of opioidergic systems in mecamylamine-precipitated nicotine
      withdrawal aversion was investigated. METHODS: Male Sprague-Dawley rats were
      chronically treated s.c. with 10 mg/kg/day (-)-nicotine tartrate using an osmotic
      minipump. After nicotine treatment for 7 days, conditioning sessions were
      performed. In the morning, the rats were treated with mecamylamine (0.3-3.0
      mg/kg, s.c.), hexamethonium (1.0-3.0 mg/kg, s.c.), naloxone (0.1-1.7 mg/kg), or
      saline (1.0 ml/kg, s.c.) in one compartment for 60 min. In the evening of the
      same day, rats were treated with the other treatments and confined to the other
      compartment for 60 min. Rats were treated with morphine (3.0 mg/kg, s.c.) or TAN
      67 (56.0 mg/kg, s.c.) 30 min prior to mecamylamine injection in the conditioning
      session. On the next day of conditioning, tests were performed. RESULTS:
      Mecamylamine, which is known to pass the blood-brain barrier, produced a dose
      dependent place aversion. However, hexamethonium, which fails to penetrate the
      blood-brain barrier, failed to produce a place aversion. Mecamylamine
      precipitated nicotine-withdrawal aversion was significantly attenuated by
      pretreatment with the mu-opioid receptor agonist morphine and the highly
      selective delta-opioid receptor agonist TAN-67, which was administered 30 min
      before mecamylamine injection in the conditioning session. Moreover, naloxone at
      doses (0.1-1.7 mg/kg) that alone failed to show a place aversion in non-treated
      rats, produced a dose-dependent place aversion in rats that had been chronically
      treated with nicotine. CONCLUSIONS: These results suggest that central opioid
      systems may be involved in nicotine-withdrawal aversion.

PMID- 10958119
TI  - A comparison of plasma alprazolam concentrations following different routes of
      chronic administration in the Sprague-Dawley rat: implications for psychotropic
      drug research.
AB  - RATIONALE: Benzodiazepines are effective in the treatment of anxiety disorders
      over a prolonged period of time. This results in relatively stable plasma
      concentrations over the course of a day. However, due to differences in drug
      clearance in rats, which generally metabolize and clear drugs much more rapidly
      than humans, it is difficult to model this steady level in rats. OBJECTIVES:
      Several methods of chronic alprazolam administration were compared to determine
      which would best result in reproducible, therapeutically relevant levels of the
      drug. METHODS: Male Sprague-Dawley rats were administered alprazolam via two
      subcutaneous routes, Alzet 2ML2 osmotic minipumps and commercially produced slow
      release pellets, for 1 week and 2 weeks, respectively. Additionally, alprazolam
      was orally administered for 2 weeks by mixing the compound into a commercially
      available liquid, fat emulsion-based diet. The use of silastic implants to
      deliver several different benzodiazepines was also evaluated in vitro. RESULTS:
      Following 7 days of alprazolam administration at 2 mg/kg per day via osmotic
      minipump, plasma concentrations in ten identically treated rats ranged from <1
      ng/ml to 97 ng/ml. Slow-release pellets produced more consistent plasma
      concentrations, but were only minimally effective at raising plasma
      concentrations. In vitro studies utilizing silastic implants containing 90 mg
      drug in 6 cm of tubing revealed stable release of only 45-55 microg/day
      alprazolam versus 625-650 microg/day diazepam. In contrast to these
      methodologies, incorporation of alprazolam into a commercially available liquid
      diet (approximately 25-150 mg/kg per day) provided consistent, dose-dependent
      increases in plasma concentrations of alprazolam and its metabolites in a range
      appropriate for mimicking clinical exposure. CONCLUSIONS: These findings indicate
      that the most effective technique to produce plasma concentrations of alprazolam
      that are reproducible, clinically pertinent, and consistent between rats is to
      incorporate the drug into a liquid diet. These findings may also be of value in
      determining dosing routes for other benzodiazepines or psychotropic drugs.

PMID- 10958120
TI  - Partial 5-HT1A receptor agonist properties of (-)pindolol in combination with
      citalopram on serotonergic dorsal raphe cell firing in vivo.
AB  - RATIONALE: Pindolol has been reported to shorten the onset of antidepressant
      action of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors
      (SSRIs) as well as to increase their efficacy. It has been postulated that
      pindolol enhances the antidepressant effect of SSRIs by blocking somatodendritic
      5-HT1A autoreceptors, thus antagonizing the SSRI-induced feedback inhibition of
      midbrain 5-HT cell firing. A recent study, however, found that pindolol
      suppresses the firing rate of central 5-HT cells, suggesting that the compound
      possesses agonistic activity at 5-HT1A autoreceptors. OBJECTIVES: The purpose of
      the present study was to investigate if acute administration of (-)pindolol
      antagonizes the decrease in firing rate of dorsal raphe 5-HT cells produced by
      acute treatment with the SSRI citalopram. METHODS: Extracellular recordings of
      single 5-HT neurons in the dorsal raphe nucleus in anaesthetized rats. RESULTS:
      Administration of 0.25 or 3.0 mg/kg (IV) (-)pindolol alone decreased the firing
      rate of a majority of the 5-HT cells studied, an effect that was reversed by the
      5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, IV). Neither 0.25 nor 3.0 mg/kg
      (-)pindolol reversed the citalopram (0.1-0.2 mg/kg. IV)-induced suppression of 5
      HT cell activity, but produced a further decrease in firing rate. In contrast,
      WAY100635 (0.1 mg/kg) completely reversed this effect of citalopram. Yet,
      pretreatment with 3.0, but not 0.25 mg/kg (-)pindolol significantly attenuated
      the acute inhibitory effect of citalopram on serotonergic cell firing.
      CONCLUSIONS: The present findings support the previous notion that (-)pindolol
      possesses prominent agonistic activity at somatodendritic 5-HT1A autoreceptors,
      but also indicate that it may possess a weak antagonistic action at these
      receptors.

PMID- 10958121
TI  - Reinstatement of extinguished drug-taking behavior in rats: effect of the kappa
      opioid receptor agonist, U69593.
AB  - RATIONALE: Results of a previous study indicated that prior administration of the
      kappa-opioid receptor agonist, U69593, blocked the ability of cocaine to
      reinstate extinguished cocaine-taking behavior. OBJECTIVES: In order to determine
      whether the effect of U69593 was specific to cocaine or was common to cocaine
      seeking produced by other dopamine uptake inhibitors, the effects of U69593 on
      cocaine seeking produced by experimenter-administered injections of cocaine, the
      dopamine uptake inhibitor, GBR 12909, or the cocaine analogs, WIN 35,428 and RTI
      55, were compared. METHODS: Reinstatement of extinguished cocaine-taking behavior
      was measured for rats that received injections of the kappa-opioid agonist,
      U69593 (0.0 or 0.32 mg/kg, SC), 15 min prior to injections of cocaine- (0.0-20.0
      mg/kg, IP), GBR 12909- (0.0-30.0 mg/kg, IP), WIN 35.428- (0.0-3.0 mg/kg, IP) or
      RTI-55 (0.0-0.50 mg/kg, IP). RESULTS: All of the drugs produced a dose-dependent
      reinstatement of extinguished cocaine-taking behavior. However, only the effects
      of cocaine and RTI-55 were attenuated by prior administration of U69593 (0.32
      mg/kg, SC). The U69593-produced attenuation of cocaine-produced cocaine seeking
      was reversed by prior administration of the kappa-opioid antagonist,
      norbinaltorphimine (30.0 microg, ICV), indicating that the effect was mediated by
      central kappa-opioid receptors. CONCLUSIONS: The failure of U69593 to attenuate
      GBR 12909- or WIN 35,428-produced cocaine seeking suggests that the effect of
      this kappa-opioid receptor agonist on cocaine seeking is not mediated by
      interactions at the dopamine transporter. The ability of U69593 to attenuate RTI
      55-produced cocaine seeking raises the possibility that kappa-opioids and cocaine
      may interact at common sites on the serotonin transporter.

PMID- 10958123
TI  - Resuscitation of severe uncontrolled hemorrhage: 7.5% sodium chloride/6% dextran
      70 vs 0.9% sodium chloride.
AB  - OBJECTIVES: Resuscitation studies of hypertonic saline using controlled and
      uncontrolled hemorrhage models yield conflicting results with regard to efficacy.
      These disparate results reflect the use of models and resuscitation regimens that
      are not comparable between studies. This study evaluated the effects of
      comparable and clinically relevant resuscitation regimens of 7.5% sodium
      chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal
      uncontrolled hemorrhage model. METHODS: Thirty-six swine (14.2 to 21.4 kg) with 4
      mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The
      animals were resuscitated with either NS or HSD administered in volumes that
      provided equivalent sodium loads at similar rates. Group II (n = 12) was
      resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12)
      received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups,
      crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a
      rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. RESULTS:
      One-hour mortality was significantly greater in group I (92%) as compared with
      group II (33%) and group III (33%) (Fisher's exact test; p = 0.004).
      Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20
      mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg)
      (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters
      between groups II and III. CONCLUSION: In this model of severe uncontrolled
      hemorrhage, resuscitation with HSD or NS, administered in volumes that provided
      equivalent sodium loads at similar rates, had similar effects on mortality,
      hemodynamic parameters, and hemorrhage from the injury site.

PMID- 10958122
TI  - Anxiolytic profile of ropinirole in the rat, mouse and common marmoset.
AB  - RATIONALE: Some features of Parkinson's disease are exacerbated by stress and
      anxiety and it is important to understand the effects of dopamine receptor
      agonists on measures of anxiety. The aim of this study was to assess the effects
      of the dopamine D2/D3 receptor agonist ropinirole in models of anxiety and
      depression in the rat, mouse and marmoset. RESULTS: In the rat elevated plus-maze
      test, ropinirole (0.01-1 mg/kg, i.p.) produced an inverted-U dose-response curve
      in the percentage time spent in the open arms. Compared with vehicle, ropinirole
      (0.1 mg/kg) had a significant anxiolytic-like effect, which was similar to that
      observed with 1.5 mg/kg diazepam. This effect was found at doses that did not
      affect motor behaviour or induce stereotypy. In the mouse black and white box
      test of anxiety, ropinirole (0.1-10 mg/kg, i.p.) increased both the rearing time
      and number of line crosses in the white section. This effect reached statistical
      significance for both measures at a dose of 0.1 mg/kg and suggests an anxiolytic
      like action of the compound. By contrast, the dopamine agonist bromocriptine (0.1
      10 mg/kg, i.p.) did not produce significant changes in these behaviours. In the
      marmoset human threat test, ropinirole (0.01-10 microg/kg, s.c.) reduced the
      number of postures at all doses tested and this reached statistical significance
      at 10 microg/kg. Ropinirole did not compromise the effect of amitriptyline in the
      Porsolt test of depression and in itself produced antidepressant-like effects.
      CONCLUSIONS: These data demonstrate that systemic administration of ropinirole
      produces anxiolytic-like effects in three separate models in the mouse, rat and
      marmoset. This may predict an action of ropinirole in man that would provide a
      superior profile of action over other presently available anti-parkinsonian
      agents.

PMID- 10958124
TI  - Patients' perceptions of route of nonsteroidal anti-inflammatory drug
      administration and its effect on analgesia.
AB  - OBJECTIVE: There is a commonly held belief among health care providers that
      patients respond better to parenteral nonsteroidal anti-inflammatory drugs
      (NSAIDs) than to oral forms by virtue of the patients' belief that getting an
      injection means they are receiving "stronger" medicine. To the authors'
      knowledge, this effect has never been adequately documented in the literature.
      The objective of this study was to compare the effects of a placebo analgesic
      injection vs placebo oral analgesia on patients with acute musculoskeletal pain.
      METHODS: A convenience sample of emergency department (ED) patients with acute
      musculoskeletal pain secondary to trauma were enrolled. Patients received 225 mL
      of orange-flavored drink containing 800 mg of ibuprofen. Patients then received
      either a physiologically inactive starch tablet resembling ibuprofen 800 mg in
      taste and appearance or a physiologically inactive saline intramuscular (IM)
      injection resembling ketorolac 60 mg. Both patients and research nurses were
      blinded to the addition of ibuprofen to the drink and the inactive nature of
      subsequent medication. Pain was evaluated at time 0 and at 30, 60, 90, and 120
      minutes on a 10-mm visual analog scale (VAS). RESULTS: Sixty-four patients
      completed the study protocol. The VAS scores between groups did not differ
      significantly at baseline or at each subsequent interval (p = 0.86). CONCLUSIONS:
      These results contradict the belief that parenteral medications confer a
      selective placebo effect stemming from patients' beliefs regarding route of
      administration and efficacy. Therefore, the routine use of IM administration of
      NSAIDs for suspected enhanced analgesia appears unwarranted.

PMID- 10958125
TI  - Impact of community intervention to reduce patient delay time on use of
      reperfusion therapy for acute myocardial infarction: rapid early action for
      coronary treatment (REACT) trial. REACT Study Group.
AB  - BACKGROUND: Reperfusion therapy for acute myocardial infarction (AMI) is a time
      dependent intervention that can reduce infarct-related morbidity and mortality.
      Out-of-hospital patient delay from symptom onset until emergency department (ED)
      presentation may reduce the expected benefit of reperfusion therapy. OBJECTIVE:
      To determine the impact of a community educational intervention to reduce patient
      delay time on the use of reperfusion therapy for AMI. METHODS: This was a
      randomized, controlled community-based trial to enhance patient recognition of
      AMI symptoms and encourage early ED presentation with resultant increased
      reperfusion therapy rates for AMI. The study took place in 44 hospitals in 20
      pair-matched communities in five U.S. geographic regions. Eligible study subjects
      were non-institutionalized patients without chest injury (aged > or =30 years)
      who were admitted to participating hospitals and who received a hospital
      discharge diagnosis of AMI (ICD 410); n = 4,885. For outcome assessment, patients
      were excluded if they were without survival data (n = 402), enrolled in
      thrombolytic trials (n = 61), receiving reperfusion therapy >12 hours after ED
      arrival (n = 628), or missing symptom onset or reperfusion times (n = 781). The
      applied intervention was an educational program targeting community organizations
      and the general public, high-risk patients, and health professionals in target
      communities. The primary outcome was a change in the proportion of AMI patients
      receiving early reperfusion therapy (i.e., within one hour of ED arrival or
      within six hours of symptom onset). Trends in reperfusion therapy rates were
      determined after adjustment for patient demographics, presenting blood pressure,
      cardiac history, and insurance status. Four-month baseline was compared with the
      18-month intervention period. RESULTS: Of 3,013 selected AMI patients, 40%
      received reperfusion therapy. Eighteen percent received therapy within one hour
      of ED arrival (46% of treated patients), and 32% within six hours of symptom
      onset (80% of treated patients). No significant difference in the trends in
      reperfusion therapy rates was attributable to the intervention, although
      increases in early reperfusion therapy rates were noted during the first six
      months of the intervention. A significant association of early reperfusion
      therapy use with ambulance use was identified. CONCLUSIONS: Community-wide
      educational efforts to enhance patient response to AMI symptoms may not translate
      into sustained changes in reperfusion practices. However, an increased odds for
      early reperfusion therapy use during the initiation of the intervention and the
      association of early therapy with ambulance use suggest that reperfusion therapy
      rates can be enhanced.

PMID- 10958126
TI  - Cocaine-associated chest pain: how common is myocardial infarction?
AB  - OBJECTIVE: Prior studies addressing the incidence of acute myocardial infarction
      (AMI) in patients with cocaine-associated chest pain have found divergent
      results. Previous prospective studies, which found approximately a 6% incidence
      of AMI, have been criticized for selection bias. This study sought to determine
      the rate of AMI in patients with cocaine-associated chest pain. METHODS: All
      patients seen in an urban university-affiliated hospital between July 1996 and
      February 1998 were identified by ICD-9 medical records search for cocaine use and
      chest pain/ acute coronary syndromes. In this system, all faculty admit all
      patients with cocaine-associated chest pain for at least 23-hour observation
      periods. Data collected included demographics, medical and cocaine use history,
      presenting characteristics, hospital course, cardiovascular complications, and
      diagnostic tests using a 119-item closed-question data instrument with high
      interrater reliability. The main outcome measure was AMI according to World
      Health Organization (WHO) criteria. RESULTS: There were 250 patients identified
      with a mean age of 33.5 +/- 8.5 years; 77% were male; 84% were African American.
      Of 196 patients tested, 185 had cocaine or cocaine metabolites in the urine
      (94%). The incidence of cardiac risk factors were: hypercholesterolemia, 8%;
      diabetes, 6%; family history, 34%; hypertension, 26%; tobacco use, 77%; prior MI,
      6%; and prior chest pain, 40%. Seventy-seven percent admitted to cocaine use in
      the preceding 24 hours: crack, 85%; IV, 2%; nasal, 6%. Twenty-five patients (10%)
      had electrocardiographic evidence of ischemia. A total of 15 patients experienced
      an AMI (6%; 95% CI = 4.1% to 8.9%) using WHO criteria. Complications were
      infrequent: bradydysrrhythmias, 0.4%; congestive heart failure, 0.4%;
      supraventricular tachycardia, 1.2%; sustained ventricular tachycardia, 0.8%.
      CONCLUSION: The incidence of AMI was 6% in patients with cocaine-associated chest
      pain. This result is identical to that found in prior prospective studies.

PMID- 10958127
TI  - Randomized, double-blind, placebo-controlled trial of diazepam, nitroglycerin, or
      both for treatment of patients with potential cocaine-associated acute coronary
      syndromes.
AB  - INTRODUCTION: To the authors' knowledge, treatment of patients with cocaine
      associated acute coronary syndromes has not been rigorously investigated in
      symptomatic patients. OBJECTIVE: To perform a randomized double-blind trial of
      diazepam, nitroglycerin, or both for treatment of patients with potential cocaine
      associated acute coronary syndromes. METHODS: Patients with potential cocaine
      associated acute coronary syndromes were randomized to treatment with either
      diazepam, nitroglycerin, or both every 5 minutes or until symptom resolution.
      Outcomes were chest pain resolution (measured by visual analog scale), and
      changes in blood pressure, pulse rate, cardiac output (L/min), cardiac index
      (L/min/m2), stroke volume (mL/beat), and stroke index (mL/beat/m2) over the 15
      minute treatment period. To adjust for seven outcomes using the Bonferroni
      correction, alpha was set at 0.007. RESULTS: Forty patients were enrolled
      (diazepam, 12; nitroglycerin, 13; both, 15). Patients had a mean age (+/-SD) of
      35.4 (+/-7.5) years; 75% were male. They presented a mean of 5 hours and 37
      minutes after cocaine use. Baseline demographics, cocaine use patterns, chest
      pain characteristics, and initial electrocardiograms were similar for all groups.
      Chest pain severity improved similarly in the three groups [-33.3 mm (+/-8.0); 
      30.7 mm (+/-7.1); -33.0 mm (+/-7.9); p = 0.6]. The stroke index decreased during
      the 15-minute treatment period for all groups (diazepam, -8.7 (+/-3.3);
      nitroglycerin, -3.1 +/- 2.8; both, -1.8 (+/-3.1) mL/beat/m2; p = 0.03). After
      adjustment for differences between baseline hemodynamic and cardiac profiles and
      multiple comparisons, there was no difference in any response to therapy over
      time for the different treatments. CONCLUSIONS: For treatment of patients with
      potential cocaine-associated acute coronary syndromes, chest pain resolutions and
      changes in cardiac performance are not different in patients treated with
      diazepam or nitroglycerin. In this study, the use of both agents did not offer
      any advantage over either agent alone.

PMID- 10958128
TI  - Clinical characteristics as predictors of recurrent alcohol-related seizures.
AB  - OBJECTIVE: To determine whether clinical data available in the emergency
      department can accurately predict a subset of patients at low risk of developing
      recurrent seizures following one or more initial alcohol-related seizures in the
      out-of-hospital arena. METHODS: This was a retrospective secondary analysis of
      data obtained from the placebo arms of two prospective, randomized trials of drug
      treatments for the prevention of recurrent alcohol-related seizures. Subjects
      with and without one or more recurrent alcohol-related seizures during the study
      period were compared according to the following characteristics: 1) age, 2)
      gender, 3) daily ethanol consumption, 4) years of ethanol abuse, 5) previous
      alcohol-related seizure, 6) previous seizure of other etiology, 7) temperature,
      8) heart rate, 9) systolic blood pressure, 10) diastolic blood pressure, 11)
      respiratory rate, and 12) ethanol level. Data were analyzed with t-tests and chi
      square where appropriate. RESULTS: One hundred five placebo-treated patients were
      analyzed and 31 (30%) developed recurrent alcohol-related seizures. None of the
      listed characteristics were statistically different between the two groups except
      for the initial ethanol level. Subjects with an ethanol level higher than 100
      mg/dL were less likely (0%) to develop recurrent seizures than patients with a
      level equal to or below 100 mg/dL (36%) (p < 0.01). CONCLUSIONS: An initial
      ethanol level higher than 100 mg/dL was significantly associated with a low risk
      for recurrent alcohol-related seizures during the observation period. No other
      low-risk clinical characteristics could be identified.

PMID- 10958129
TI  - A comparison of data sources for motor vehicle crash characteristic accuracy.
AB  - OBJECTIVE: To determine the accuracy of police reports (PRs), ambulance reports
      (ARs), and emergency department records (EDRs) in describing motor vehicle crash
      (MVC) characteristics when compared with an investigation performed by an
      experienced crash investigator trained in impact biomechanics. METHODS: This was
      a cross-sectional, observational study. Ninety-one patients transported by
      ambulance to a university emergency department (ED) directly from the scene of an
      MVC from August 1997 to April 1998 were enrolled. Potential patients were
      identified from the ED log and consent was obtained to investigate the crash
      vehicle. Data describing MVC characteristics were abstracted from the PR, AR, and
      medical record. Variables of interest included restraint use (RU), air bag
      deployment (AD), and type of impact (TI). Agreements between the variables and
      the independent crash investigation were compared using kappa. Interrater
      reliability was determined using kappa by comparing a random sample of 20
      abstracted reports for each data source with the originally abstracted data.
      RESULTS: Agreement using kappa between the crash investigation and each data
      source was 0.588 (95% CI = 0.508 to 0.667) for the PR, 0.330 (95% CI = 0.252 to
      0.407) for the AR, and 0.492 (95% CI = 0.413 to 0.572) for the EDR. Variable
      agreement was 0.239 (95% CI = 0.164 to 0.314) for RU, 0.350 (95% CI = 0.268 to
      0.432) for AD, and 0.631 (95% = 0.563 to 0.698) for TI. Interrater reliability
      was excellent (kappa > 0.8) for all data sources. CONCLUSIONS: The strength of
      the agreement between the independent crash investigation and the data sources
      that were measured by kappa was fair to moderate, indicating inaccuracies. This
      presents ramifications for researchers and necessitates consideration of the
      validity and accuracy of crash characteristics contained in these data sources.

PMID- 10958130
TI  - A descriptive analysis of 290 liver transplant patient visits to an emergency
      department.
AB  - OBJECTIVE: To provide a descriptive analysis of emergency department (ED)
      presentations and management of orthotopic liver transplant (OLT) patients.
      METHODS: A retrospective chart review was performed of OLT patients presenting to
      the University of California at Los Angeles (UCLA) ED during 1995. The sole
      inclusion criterion was receiving an OLT within three years prior to the ED
      visit. Data describing chief complaint(s), history of present illness, physical
      findings, laboratory results, imaging studies, and final diagnoses were
      collected. RESULTS: One hundred forty-three patients accounted for a total of 290
      ED visits. The patients had a mean age of 37 years (range 3 months to 74 years)
      and presented at mean post-OLT duration of 9 months (range 2 weeks to 34 months).
      There were 660 presenting complaints, of which abdominal (39%), fever (17%),
      respiratory (13%), and neurologic (11%) symptoms were the most common. There were
      478 final diagnoses, of which abdominal (27%), infectious (24%), and metabolic
      (11%) disorders were the most common. Eighty-four percent of ED visits resulted
      in extensive diagnostic testing and 69% resulted in hospitalization. CONCLUSIONS:
      Serious illnesses with nonspecific presentations were frequently encountered in
      this study population. These factors resulted in a majority of the patients'
      undergoing extensive diagnostic evaluations and being hospitalized.

PMID- 10958131
TI  - Clinical presentations and prognostic factors of a glyphosate-surfactant
      herbicide intoxication: a review of 131 cases.
AB  - OBJECTIVE: Suicide attempts with agricultural chemicals are common in southern
      Taiwan. Among them, glyphosate-surfactant herbicide (GlySH) intoxication has been
      encountered with increasing frequency. Although a number of reports have
      described the clinical course and outcomes following ingestion, predictors of
      serious complications and mortality have not been elucidated. The purpose of this
      study was to define predictors of serious complications and probable mortality.
      METHODS: This was a retrospective study of 131 GlySH-intoxicated patients treated
      at the National Cheng Kung University Hospital from 1988 to 1995. Medical charts
      were reviewed and clinical and laboratory variables were abstracted, looking for
      predictors of mortality. RESULTS: The most common symptoms included sore throat
      (79.5%), and nausea with or without vomiting (73.8%). The most common laboratory
      findings were leukocytosis (68.0%), low serum bicarbonate (48.1%), and acidosis
      (35.8%). Overall, 11 of 131 patients (8.4%) died; the mean +/- SEM time to death
      was 2.8 +/- 0.8 days after presentation. When comparing the clinical and
      laboratory characteristics among the survivor and fatality groups, significant
      differences were identified. Respiratory distress, pulmonary edema, respiratory
      distress necessitating intubation, shock (systolic blood pressure less than 90 mm
      Hg), altered consciousness, abnormal chest x-ray, renal failure necessitating
      hemodialysis, larger amount of ingestion (>200 mL), and hyperkalemia were
      predictors highly associated with poor outcomes and mortality. Using multiple
      logistic regression, three predictors were identified, which may predict
      mortality in severely intoxicated patients. CONCLUSIONS: In managing patients who
      have larger amount of GlySH ingestion, airway protection, early detection of
      pulmonary edema, and prevention of further pulmonary damage and renal damage
      appear to be of critical importance.

PMID- 10958132
TI  - Planning recommendations for international emergency medicine and out-of-hospital
      care system development.
AB  - OBJECTIVES: To present suggestions on planning for development of emergency
      medicine (EM) and out-of-hospital care in countries that are in an early phase of
      this process, and to provide basic background information for planners not
      already familiar with EM. METHODS: The techniques and programs used by the
      authors and others in assisting in EM development in other countries to date are
      described. CONCLUSIONS: Some aspects of EM system development have applicability
      to most countries, but other aspects must be decided by planners based on country
      specific factors. Because of the very recent initiation of many EM system
      development efforts in other countries, to the authors' knowledge there have not
      yet been extensive evaluative reports of the efficacy of these efforts. Further
      studies are needed on the relative effectiveness and cost-benefit of different EM
      development efforts.

PMID- 10958133
TI  - Clinical pearls: painful tongue swelling.

PMID- 10958135
TI  - The complicated meaning of placebo and placebo effect.

PMID- 10958134
TI  - Clinicopathological conference: weakness in the knees.

PMID- 10958136
TI  - Moonlighting and emergency medicine: raising the standard.

PMID- 10958137
TI  - SAEM position statement on the qualifications for unsupervised emergency
      department care. SAEM Board of Directors. Society for Academic Emergency
      Medicine.

PMID- 10958138
TI  - CORD position statement on moonlighting. CORD Board of Directors. Council of
      Emergency Medicine Residency Directors.

PMID- 10958139
TI  - Bench to bedside: tumor necrosis factor-alpha: from inflammation to
      resuscitation.
AB  - Proinflammatory mediators such as tumor necrosis factor-alpha (TNF) have been
      implicated in the pathophysiology in a number of acute disease states. Tumor
      necrosis factor-alpha can contribute to cell death, apoptosis, and organ
      dysfunction. Tumor necrosis factor-alpha can be generated with sepsis or ischemia
      reperfusion by activation of cell mitogen-activated protein kinases and nuclear
      factor kappa B, leading to TNF production. A number of strategies to modulate TNF
      have been recently explored, including factors directed toward mitogen-activated
      protein kinases, TNF transcription, anti-inflammatory ligands, heat shock
      proteins, and TNF-binding proteins. However, TNF may also play an important role
      in the adaptive response to injury and inflammation. Control of the deleterious
      effects of TNF and other proinflammatory cytokines represents a realistic goal
      for clinical emergency medicine. The purpose of this article is to provide a
      background of relevance to emergency medicine academicians on the production and
      regulation of TNF, the acute effects of TNF on pathophysiology, and the rationale
      for therapeutic interventions directed toward TNF and the clinical experience
      with these strategies.

PMID- 10958141
TI  - Bedside emergency department ultrasonography in the evaluation of ocular
      pathology.
AB  - The number of potential uses of emergency department (ED) ultrasound is growing.
      This brief report describes its use in two ED patients who presented with acute
      ocular pathology. The diagnoses were quickly made with ED ultrasound, and
      subsequently confirmed with more traditional methods of ocular evaluation.

PMID- 10958140
TI  - Mucormycosis manifesting as proptosis and unilateral blindness.
AB  - A 51-year-old woman presented to the emergency department (ED) of another
      institution with sudden onset of blindness in the left eye. The patient was found
      to have no light perception in the left eye and a marked chemosis occurring
      several days after a fall. She was transferred to the hospital for ophthalmologic
      evaluation. Upon careful history and physical examination, the diagnosis of
      rhinocerebral mucormycosis was considered and urgent ophthalmology and
      otolaryngology consults were obtained. The patient underwent extensive surgical
      debridement and pharmacologic treatment. The diagnosis was confirmed by
      pathological specimens. In this case report, the clinical presentation,
      pathogenesis, diagnostic workup, and ED management of mucormycosis are discussed,
      highlighting the possible diagnostic and therapeutic pitfalls that are most
      pertinent to the emergency physician.

PMID- 10958142
TI  - Home care and emergency medicine: a pilot project to discharge patients safely
      from the emergency department.
AB  - OBJECTIVES: To describe in detail the implementation of an acute care home care
      program (quick response program; QRP) for the emergency department (ED). METHODS:
      A prospective observational study with key process and outcome indicators,
      including number of referrals, time to initiate service, type of home care
      provided, number of return patients to the ED, and outcome for all patients,
      defined at the beginning of the project. Patients are identified for the QRP and
      services are in place within four hours of patient discharge. RESULTS: Of 177
      eligible patients, 121 were entered into the program. Sixty-eight percent were
      more than 65 years old, and 54% lived alone. All patients met the time target of
      services in place within four hours of discharge from the ED. Patient
      satisfaction was high as measured by an independent survey instrument. Fifty
      percent of the patients required no further service after the QRP, but 20% were
      admitted to hospital within 30 days. CONCLUSIONS: A QRP can be successfully
      implemented in the ED to discharge patients home, most of whom would have been
      admitted to hospital.

PMID- 10958143
TI  - Effect of exogenous melatonin on mood and sleep efficiency in emergency medicine
      residents working night shifts.
AB  - OBJECTIVE: To determine whether melatonin taken prior to attempted daytime sleep
      sessions will improve daytime sleep quality, nighttime sleepiness, and mood state
      in emergency medicine (EM) residents, changing from daytime to nighttime work
      schedules. METHODS: A prospective, randomized, double-blind crossover design was
      used in an urban emergency department. Emergency medicine residents who worked
      two strings of nights, of at least three nights' duration each, and separated by
      at least one week of days were eligible. Subjects were randomized to receive
      either melatonin 1 mg or placebo, 30 to 60 minutes prior to their daytime sleep
      session, for three consecutive days after each night shift. Crossover to the
      other agent occurred during their subsequent night shifts. Objective measures of
      quality of daytime sleep were obtained using the Actigraph 1000. This device
      measures sleep motion and correlates with sleep efficiency, total sleep time,
      time in bed, and sleep latency. The Profile of Mood States (POMS) and the
      Stanford Sleepiness Scale (SSS) were also used to quantify nighttime mood and
      sleepiness. RESULTS: Among the 19 volunteers studied, there was no difference in
      sleep efficiency (91.16% vs 90.98%, NS), sleep duration (379.6 min vs 342.7 min,
      NS), or sleep latency (7.59 min vs 6.80 min, NS), between melatonin and placebo,
      respectively. In addition, neither the POMS total mood disturbance (5.769
      baseline vs 12.212 melatonin vs 5.585 placebo, NS) nor the SSS (1.8846 baseline
      vs 2.2571 melatonin vs 2.1282 placebo, NS) demonstrated a statistical difference
      in nighttime mood and sleepiness between melatonin and placebo. CONCLUSIONS:
      There are no beneficial effects of a 1-mg melatonin dose on sleep quality,
      alertness, or mood state during night shift work among EM residents.

PMID- 10958144
TI  - EMCyberSchool: an evaluation of computer-assisted instruction on the Internet.
AB  - OBJECTIVES: To test the hypothesis that integration of the EMCyberSchool, a
      computer-assisted instruction (CAI) tool available on the Internet, into the
      curriculum of a senior medical student subinternship in emergency medicine (EM)
      would improve exam scores and course satisfaction. METHODS: Students were
      prospectively randomized, by four-week blocks, into a CAI group and a no-CAI
      group. All students were surveyed on previous computer experience and their use
      and opinion of the EMCyberSchool. RESULTS: Completed data were obtained from 100
      of 120 students. Sixty-five percent of the students said they wanted CAI as an
      adjunct to their course curricula; only 28% actually used the educational tool.
      The students who used the site rated it useful (4.2/5), easy to use (4.4/5), and
      easy to access (4.1/5). Of the students who had access, and chose not to use the
      EMCyberSchool, 77.8% reported not having enough time as the reason for not using
      the site. The mean exam scores were 72.8% for the students in the CAI group and
      68.2% for those in the no-CAI group (p = 0.058). In the CAI group, 77.5% (31/40)
      of the students rated the course as outstanding or excellent; compared with 66%
      (33/50) in the no-CAI group (p = 0.23). CONCLUSIONS: Although desired, it remains
      unclear whether CAI on the Internet is a useful adjunct for teaching EM to
      medical students.

PMID- 10958146
TI  - Roles of intracortical inhibition in the formation of spatially tuned delay
      period activity of prefrontal cortical neurons: computational study.
AB  - 1. This paper proposes a computational circuit model of the prefrontal cortex,
      with which computer simulations of the delay-period activity of the prefrontal
      cortical neurons are made. 2. The aim of this study is to address the question as
      to how the two types of local inhibition (the parallel inhibition and the anti
      parallel inhibition), which were suggested previously and are assumed in this
      model, contribute to the formation of spatially tuned delay-period activity. 3.
      The results suggest that the parallel inhibition regulates the level of the delay
      period activity, while the anti-parallel inhibition contributes to the sharpening
      of the activity profile in the delay period. 4. This study found a new prediction
      that the weakened parallel inhibition causes stronger anti-parallel inhibition of
      the inactive pyramidal cells due to the disinhibition of the active pyramidal
      cells. 5. These results suggest the important roles of the intracortical
      inhibition in the formation and maintenance of spatial working memory.

PMID- 10958145
TI  - Standardized letter of recommendation for residency application.

PMID- 10958147
TI  - Proton magnetic resonance spectroscopy of lenticular nuclei in simple
      schizophrenia.
AB  - 1. The lenticula nuclei have been suggested to be the site of structural and
      functional abnormalities in schizophrenia. 2. Recently, several studies involving
      proton magnetic resonance spectroscopy (1H MRS) showed that the ratio of N-acetyl
      aspartate (NAA) to choline-containing compounds (Cho) was significantly reduced
      in the basal ganglia region in patients with schizophrenia. 3. Simple
      schizophrenia is characterized by social withdrawal and affective flattening, but
      not by prominent catatonic, hebephrenic or paranoid features. 4. We studied,
      using 1H MRS, the lenticula nuclei of 10 patients with simple schizophrenia, and
      10 age- and sex-matched healthy controls. 5. No differences between the patients
      and the controls were found in any of the measured ratios, i.e. Cho/Cr, NAA/Cr
      and NAA/Cho. 6. Our results suggest the normal viability of neuronal cells, as
      found on quantification of NAA, Cr and Cho, in the lenticular nuclei of patients
      with simple schizophrenia. 7. The pathophysiology of simple schizophrenia may be
      different from those of other types of schizophrenia.

PMID- 10958148
TI  - Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic
      impairment.
AB  - 1. The atypical antipsychotic quetiapine ('Seroquel') provides equivalent
      efficacy to the typical antipsychotics chlorpromazine and haloperidol in the
      short-term treatment of schizophrenia. Moreover, the incidence of extrapyramidal
      symptoms associated with quetiapine treatment is equivalent to that observed with
      placebo treatment, which may lead to increased patient compliance with quetiapine
      compared with typical antipsychotics. 2. This report presents the results from
      two small studies aimed at determining the pharmacokinetics of quetiapine in
      nonpsychotic subjects with renal or hepatic impairment. Equal numbers of impaired
      subjects and healthy control subjects were administered a single, 25 mg dose of
      quetiapine, and plasma concentrations were determined up to 48 hr after dosing.
      3. No clinically significant differences were found when the pharmacokinetic
      parameters for subjects with renal or hepatic impairment were compared with those
      for healthy control subjects. The results indicate that dosage adjustment of
      quetiapine may be unnecessary in psychotic patients with decreased renal
      function. 4. In subjects with hepatic impairment related to alcoholic cirrhosis,
      the results suggest that no change is needed in the recommended quetiapine
      starting dose (25 mg). However, because of a noted inter-subject variability in
      the clearance of quetiapine in the cirrhotic group, it is recommended that dose
      escalation be performed with caution in patients with hepatic impairment. 5. The
      single dose of quetiapine 25 mg generally was well tolerated in nonpsychotic
      subjects in good health or with either renal or hepatic impairments. Quetiapine
      also had no effect on the endogenous creatinine clearance of renally impaired or
      healthy control subjects.

PMID- 10958149
TI  - Effects of tobacco smoking on topographic EEG and Stroop test in smoking deprived
      smokers.
AB  - 1. Quantitative electroencephalography (EEG) was used to measure human brain
      electrical changes produced by tobacco deprivation and smoking. Sixteen scalp
      cortical recording sites monitored regional changes in brain activity. 2. The
      quantitative EEG was subdivided into delta, theta, alpha1, alpha2, beta1 and
      beta2 bands for topographic mapping. A demanding version of the Stroop test was
      used to determine tobacco smoking effects on attention. The version used was more
      difficult than that used in previously reported studies. 3. Healthy drug and
      substance free adult male and female volunteers were divided into nonsmoker (n=7)
      and smoker (n=7) groups according to their smoking status. They were instructed
      to abstain from tobacco products for at least 12 hr overnight before the next
      morning's experiment. 4. EEG was recorded before and after smoking either a fake
      placebo cigarette for nonsmokers or the cigarette of their choice for smokers.
      Subjects were also asked to perform the Stroop test before and after smoking the
      placebo or tobacco cigarette. 5. The results showed that tobacco smoking
      significantly depressed delta and increased alpha2 and beta1 activity and
      slightly increased the Stroop effect. Although smoking one cigarette stimulated
      brain electrical activity of smoking deprived smokers, it did not improve
      performance on a difficult Stroop test.

PMID- 10958150
TI  - Animal models: trait or state measure? The test-retest reliability of the
      elevated plus-maze and behavioral despair.
AB  - 1. The use of animal models in certain types of psychobiological studies (for
      instance, the relationship between anxiety and depression) requires that the
      behavior measured is stable over time. 2. The test-retest reliability of the
      elevated plus-maze indexes of anxiety and the immobility time in the behavioral
      despair were evaluated. 3. The behavior of two groups of drug naive mice was
      measured on two occasions on the same test, 1 week apart, on the elevated plus
      maze or on the behavioral despair and then the intraclass correlation coefficient
      and kappa were calculated. 4. These behaviors showed a very low intraclass
      correlation coefficient (0.02 - 0.05) and low kappa (-0.08 - 0.21) in the test
      retest design, which suggest a poor reliability of these measures. 5. These
      results suggest that the behavioral parameters of the elevated plus-maze and the
      behavioral despair are not stable and therefore they are possibly more related to
      state than trait characteristics. Therefore they appear to be not appropriate to
      evaluate trait characteristics which are supposed to be stable over time without
      treatment.

PMID- 10958151
TI  - Influence of benzodiazepines on body weight and food intake in obese and lean
      Zucker rats.
AB  - 1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally altered
      in obese (fa/fa) Zucker rats, plays an important role in controlling energy
      balance within the central nervous system. 2. GABA receptors seem to be involved
      in the dysfunction of the hypothalamic energy homeostasis-controlling mechanisms
      in these animals due to a genetically-induced defect of the leptin-neuropeptide Y
      system. 3. To shed further light on the possible role played by the GABA system
      in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agonists
      (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were administered
      intraperitoneally in obese and lean Zucker rats. 4. Body weight gain was reduced
      by the BDZ agonists in both phenotypes, and one receptor-agonist (diazepam)
      lowered insulin concentration in obese rats. In GABA-antagonist-treated obese
      rats, the daily amount of body weight gain and food intake acquired an
      oscillatory rhythm similar to that of normal rodents. 5. By demonstrating the
      role of BDZ receptors, these findings may help clarify the pathophysiology of
      obesity and insulin resistance in fatty Zucker rats.

PMID- 10958152
TI  - Combined 5-HT2/D2 receptor blockade inhibits the firing rate of SNR neurons in
      the rat brain.
AB  - 1. The aim of the present study was to evaluate the contribution of serotonin (5
      HT) and dopamine (DA) receptor antagonism to the distinct inhibitory effects of
      the atypical antipsychotics clozapine and risperidone on SNR neurons, we have
      shown previously. 2. Utilizing extracellular recordings in the SNR in chloral
      hydrate anaesthetized rats, raclopride, a selective DA D2/D3 receptor antagonist
      and LY 53857, a 5-HT2A:2c receptor antagonist were studied separately and in
      combination for their effects on the firing rate of the SNR neurons. 3. Both
      raclopride and LY 53857 induced a slight but significant increase in the firing
      rate of the SNR neurons in a limited dose range. 4. Upon pretreatment with a
      single dose of raclopride, LY 53857 induced a dose-dependent inhibitory effect on
      the firing rate of the SNR neurons. 5. Concurrent 5-HT2 and moderate DA D2
      receptor antagonism can mimic the in vivo effects of the atypical antipsychotics
      clozapine and risperidone on the firing rate of SNR neurons.

PMID- 10958153
TI  - Cholinergic modulation of inhibitory avoidance impairment induced by paradoxical
      sleep deprivation.
AB  - 1. Male Wistar rats were submitted to paradoxical sleep deprivation for 96 hr by
      a modified multiple platform technique. 2. Training of step-through inhibitory
      avoidance was performed immediately after the last day of paradoxical sleep
      deprivation. Twenty-four hr after training the animals were submitted to the
      retention test. 3. In Experiment 1, pilocarpine (4 mg/kg, i.p.) or atropine (4
      mg/kg, i.p.) were administered daily during the paradoxical sleep deprivation
      period. Pilocarpine, but not atropine, reversed the impairment induced by PS
      deprivation. 4. In Experiment 2, pilocarpine (4, 8 and 12 mg/kg, i.p.) was
      injected 1 hr before training in order to verify if the reversal of memory
      impairment was an effect secondary to residual enhanced blood levels of
      pilocarpine during training. Acute treatment with pilocarpine, in any dose, did
      not reverse the impairment produced by paradoxical sleep deprivation 5.
      Activation of the cholinergic system during the period of deprivation is able to
      prevent memory deficits induced by paradoxical sleep deprivation.

PMID- 10958154
TI  - Regulation by chronic treatment with cabergoline of dopamine D1 and D2 receptor
      levels and their expression in the striatum of Parkinsonian-monkeys.
AB  - 1. Chronic treatment for one month with the long-acting dopamine D2-like agonist
      cabergoline (0.25 mg/kg s.c. every 48 hours), had despite partial tolerance,
      sustained antiparkinsonian activity in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) Parkinsonian monkeys (Macaca fascicularis). 2.
      Cabergoline treatment decreased by half striatal D2 receptor binding density
      measured by [3H]spiperone autoradiography versus untreated MPTP monkeys. No
      change in D2 mRNA measured by in situ hybridization and D2 receptor
      immunostaining was observed. 3. No change in either D1 receptor binding density
      or D1 receptor mRNA levels was observed in cabergoline-treated MPTP-monkeys
      compared to untreated MPTP-monkeys, suggesting receptor subfamily specificity of
      cabergoline. 4. The present results suggest that the cabergoline-induced
      behavioral partial tolerance is accompanied by a decrease in D2 receptor binding
      but not due to alterations in the steady state of D2 mRNA levels.

PMID- 10958155
TI  - Second generation effects of maternal alcohol consumption during pregnancy in
      rats.
AB  - 1. Previous studies have shown that when female rats are administered alcohol
      during pregnancy there are adverse effects on their progeny, including decreased
      birth weight and delayed neuromotor development. Evidence from several sources
      suggests alcohol exposure may contribute to cytogenetic abnormalities, suggesting
      the possibility of cross generational effects from prenatal exposure. 2. On day 1
      of gestation female rats were randomly allocated to the Alcohol group, which
      received a liquid diet containing 5% (v/v) ethanol solution until parturition,
      the Sucrose control group, which received an identical diet, except that sucrose
      had been isocalorically substituted for ethanol, or the Chow control, which
      received standard laboratory chow. 3. When the offspring of these rats reached
      adulthood they were mated with drug-free rats and the development of their
      offspring was monitored. 4. In comparison with female pups whose sires had been
      exposed to alcohol in utero, the weight of pups descended from fetally-exposed
      dams increased more slowly from day 1 to day 7. 5. At five days of age,
      significant differences favouring the two control groups were found in latency to
      right for pups descended from fetally-exposed dams. 6. These data suggest that
      the effects of prenatal exposure to alcohol are more pervasive than previously
      thought and affect female pups to a greater extent than males.

PMID- 10958156
TI  - Effects of cocaine self-administration on plasma corticosterone in rats:
      relationship to hippocampal type II glucocorticoid receptors.
AB  - 1. The effects of chronic (i.e., 30-day), high-dose (i.e., 1.0 mg/kg/infusion)
      intravenous cocaine self-administration and non-contingent infusions of cocaine
      and saline on plasma corticosterone and hippocampal Type II glucocorticoid
      receptors (GR) were investigated in adult male Wistar rats implanted with
      indwelling jugular catheters using a self-administration/yoked infusion triad
      design. 2. In self-administering rats and rats receiving yoked infusions of
      cocaine, basal corticosterone measured 24 hours after the experimental sessions
      was reduced relative to yoked-saline controls and to pre-acquisition values. 3.
      In contrast, corticosterone measured immediately following the self
      administration sessions remained unaltered throughout the course of the
      experiment. 4. In cocaine self-administering rats, the effects on basal
      corticosterone were observed earlier than they were in rats receiving yoked
      infusions of cocaine. 5. The effects of self-administered and yoked cocaine were
      associated with statistically non-significant increases in hippocampal GR density
      relative to yoked-saline controls as measured by Western blot analysis using the
      anti-GR monoclonal antibody BuGR2.

PMID- 10958157
TI  - Electrophysiological characterization of CGP68730A a N-methyl-D-aspartate
      antagonist acting at the strychnine-insensitive glycine site.
AB  - 1. Electrophysiological experiments were performed in vitro and in vivo. Voltage
      clamp recordings were done in Xenopus oocytes. Extracellular recordings were done
      in vitro in the neocortical slice and in the CA1 region of the hippocampal slice
      and in vivo in the CA1 region of the hippocampus of the anaesthetized rat. 2. In
      oocytes expressing either the human NMDAR1A/2A or 1A/2B subunit combinations,
      CGP68730A [sodium (-)-9-bromo-2,3,6,7-tetrahydro-5,6-dioxo-5H-pyrazino[1,2,3-de]
      1,4-benzo thiazine-3-acetic acid] antagonized L-glutamate / glycine induced
      currents with calculated IC50s of 20.5 and 81.6 nM, respectively. 3. In vitro,
      CGP68730A was tested on NMDA induced depolarizations in the neocortical slice
      preparation and on epileptiform activity in hippocampal slices bathed in Mg2+
      free-medium, which is known to be NMDA mediated. In both in vitro models
      CGP68730A exhibited antagonistic effects on the NMDA receptor mediated responses.
      4. In vivo CGP68730A was tested on NMDA induced excitations in the CA1 region.
      CGP68730A abolished NMDA induced excitations when applied microiontophoretically.
      However, only weak effects on NMDA induced excitation were observed after
      systemic administration at 100 mg/kg i.v.. These results indicate that CGP68730A
      has poor central nervous system bioavailability. 5. In oocytes, an increase in
      the glycine concentration from the EC80 to the EC95.99 shifted the inhibition
      curves for CGP68730A to the right. Furthermore, in neocortical slices and in
      anaesthetized rats CGP68730A inhibited NMDA mediated depolarizations, and this
      effect could be reversed by the addition of the glycine mimetic D-serine. This
      indicates that these effects of CGP68730A are mediated by an action on the
      strychnine-insensitive glycine site. 6. Selectivity tests in oocytes and in the
      neocortical slice preparation, using NMDA, kainate and AMPA showed that CGP68730A
      was selective in antagonizing NMDA receptor mediated responses. In oocytes, the
      compound was about 1000 times less potent on the rat GluR3 and the human GluR6
      receptors than on the human NMDAR1A/2A subunit combination. In the neocortical
      slice preparationCGP68730A had no effects on AMPA or kainate induced
      depolarizations at concentrations of 3 and 10 microM. At 30 microM CGP68730A
      reduced the effects of each of the three agonists tested. 7. Thus, CGP68730A
      seems to be a selective antagonist at the strychnine-insensitive glycine
      coagonist site of the NMDA receptor. However, the compound showed no obvious
      central NMDA antagonistic effects following intravenous application.

PMID- 10958158
TI  - Dynamic interactions between integrative physiology and molecular medicine: the
      key to understand the mechanism of action of aldosterone in the kidney.
AB  - Our objective is to illustrate how an approach that integrates new insights from
      molecular biology and traditional physiology can lead to the development of new
      concepts. This dynamic interaction is illustrated by examining the steps taken to
      improve our understanding of the renal actions of aldosterone. We began by
      defining the big picture of what aldosterone does in the kidney. This led to the
      conclusion that aldosterone must at times become a sodium chloride-retaining
      hormone, while at other times it must function primarily or exclusively as a
      kaliuretic hormone. The second step was to define the major molecular actions of
      this hormone. Acting on the principal cells in the cortical collecting duct
      (CCD), aldosterone leads to the insertion of active epithelial sodium ion
      channels (ENaC) in their luminal membranes. This active ENaC, however, does not
      distinguish between the two major renal actions of aldosterone. Accordingly, we
      returned to integrative physiology and examined a possible role of renal and non
      renal events. We implicated the potential importance of the delivery of
      bicarbonate ions to the CCD to determine which effect of aldosterone will become
      manifest. This, however, required that we reconsider some of the traditional
      views in interpretation of acid-base balance. At the clinical level, this global
      view can help us understand why, for example, a low dietary intake of potassium
      salts might predispose a person to an elevated blood pressure. Using a similar
      approach, it is possible to understand how the risk of the formation of kidney
      stones can be minimized.

PMID- 10958159
TI  - Aminoglycosides inhibit hormone-stimulated Mg2+ uptake in mouse distal convoluted
      tubule cells.
AB  - The clinical use of aminoglycosides often leads to renal magnesium wasting and
      hypomagnesemia. Of the nephron segments, both the thick ascending limb of Henle's
      loop and the distal tubule play significant roles in renal magnesium conservation
      but the distal convoluted tubule exerts the final control of urinary excretion.
      An immortalized mouse distal convoluted tubule (MDCT) cell line has been
      extensively used to study the cellular mechanisms of magnesium transport in this
      nephron segment. Peptide hormones, such as parathyroid hormone (PTH), glucagon,
      calcitonin, and arginine vasopressin (AVP) stimulate Mg2+ uptake in MDCT cells
      that is modulated by extracellular polyvalent cations, Ca2+ and Mg2+. The present
      studies determined the effect of aminoglycosides on parathyroid hormone (PTH)
      mediated cAMP formation and Mg2+ uptake in MDCT cells. Gentamicin, a prototypic
      aminoglycoside, elicited transient increases in intracellular Ca2+ from basal
      levels of 102 +/- 13 nM to 713 +/- 125 nM, suggesting a receptor-mediated
      response. In order to determine Mg2+ transport, MDCT cells were Mg(2+)-depleted
      by culturing in Mg(2+)-free media for 16 h and Mg2+ uptake was measured by
      microfluorescence after placing the depleted cells in 1.0 mM MgCl2. The mean rate
      of Mg2+ uptake, d([Mg2+]i)/dt, was 138 +/- 24 nM/s in control MDCT cells.
      Gentamicin (50 microM) did not affect basal Mg2+ uptake (105 +/- 29 nM/s), but
      inhibited PTH stimulated Mg2+ entry, decreasing it from 257 +/- 36 nM/s to 108 +/
      42 nM/s. This was associated with diminished PTH-stimulated cAMP formation, from
      80 +/- 2.5 to 23 +/- 1 pmol/mg protein x 5 min. Other aminoglycosides such as
      tobramycin, streptomycin, and neomycin also inhibited PTH-stimulated Mg2+ entry
      and cAMP formation. As these antibiotics are positively charged, the data suggest
      that aminoglycosides act through an extracellular polyvalent cation-sensing
      receptor present in distal convoluted tubule cells. We infer from these studies
      that aminoglycosides inhibit hormone-stimulated Mg2+ absorption in the distal
      convoluted tubule that may contribute to the renal magnesium wasting frequently
      observed with the clinical use of these antibiotics.

PMID- 10958160
TI  - Modeling the large-scale geometry of human coronary arteries.
AB  - Two principles suffice to model the large-scale geometry of normal human coronary
      arterial networks. The first principle states that artery diameters are set to
      minimize the power required to distribute blood through the network. The second
      principle states that arterial tree geometries are set to globally minimize the
      lumen volume. Given only the coordinates of an arterial tree's source and
      "leaves", the model predicts the nature of the network connecting the source to
      the leaves. Measurements were made of the actual geometries of arterial trees
      from postmortem healthy human coronary arteriograms. The tree geometries
      predicted by the model look qualitatively similar to the actual tree geometries
      and have volumes that are within a few percent of those of the actual tree
      geometries. Human coronary arteries are therefore within a few percent of perfect
      global volume optimality. A possible mechanism for this near-perfect global
      volume optimality is suggested. Also, the model performs best under the
      assumption that the flow is not entirely steady and laminar.

PMID- 10958162
TI  - Increased body fat in streptozotocin diabetic rats treated with intensive
      subcutaneous insulin therapy vs. islet transplantation.
AB  - The continued development of novel insulin treatment is predicated on the
      hypothesis that strict glycemic control is necessary to prevent the secondary
      complications of diabetes. Although dramatically successful in reducing selected
      secondary complications, intensive insulin therapy has consequences. These
      include hypoglycemia, weight gain, and body fat accumulation. In the present
      studies we compared a model of intensive insulin therapy in diabetic rats and
      contrasted weight gain and body fat accumulation with pancreatic islet
      transplantation. Female Wistar Furth rats (173 g) administered streptozotocin (55
      mg x kg(-1), iv) remained diabetic (DB) for four or nine weeks. At week three, a
      third group was transplanted (TRAN) with islets of Langerhans (3519 +/- 838 150
      microm islets); one week later group four began intensive subcutaneous insulin
      therapy (ISIT; 4 x 0.5-1.0 U regular insulin x day(-1)). Within one week ISIT
      rats had normalized plasma glucose; levels were not different from age matched
      controls (CN) or TRAN animals (ISIT 10.6 +/- 1.7, CN 7.2 +/- 0.4, TRAN 7.7 +/-
      0.8 mmol x L(-1), P > 0.05). The cumulative occurrence of one episode of
      hypoglycemia (< 2.8 mmol x L(-1)) occurred in 50% of ISIT rats. At study
      termination, body weight of ISIT and CN rats did not differ (199 +/- 4 vs. 207 +/
      3, P > 0.05). While carcass protein content was similar for TRAN, ISIT, and CN
      animals, the body fat of ISIT animals was 24% greater than in CN rats and 21%
      greater than in TRAN rats (P < 0.05). Correlation of body fat vs. plasma glucose
      illustrated hypoglycemia contributed to the body fat gain of ISIT rats (n = 8, r
      = -0.70, P = 0.0535). These studies illustrate a disproportionate gain of body
      fat from ISIT, an effect not observed with islet transplantation. Thus, the
      metabolic benefit ascribed to islet transplantation appears related to the
      absence of hypoglycemia.

PMID- 10958161
TI  - Vasodilator responses to ATP and UTP are not dependent on nitric oxide release,
      K+(ATP) channel activation, or the release of vasodilator prostaglandins in the
      hindlimb vascular bed of the cat.
AB  - The effects of the purinergic agonists, ATP, ATPgammaS, UTP, and 2-Met-Thio AP,
      were investigated in the hindlimb vascular bed of the cat. Under constant-flow
      conditions, injections of the purinergic agonists into the perfusion circuit
      elicited dose-related decreases in perfusion pressure. The order of potency was 2
      Met-Thio ATP > ATPgammaS > ATP > UTP. In contrast, injections of GTPgammaS, cAMP,
      UDP, and UMP had no effect. Vasodilator responses to ATP, ATPgammaS, UTP, and 2
      Met-Thio ATP were increased in duration by the cAMP phosphodiesterase inhibitor
      rolipram, whereas the cGMP phosphodiesterase inhibitor zaprinast had no effect.
      Responses to the purinergic agonists were not altered by nitric oxide synthase
      inhibitors, K+(ATP) channel antagonists, cyclooxygenase inhibitors, or agents
      that interfere with the actions of the adrenergic nervous system. These data
      suggest that ATP, ATPgammaS, UTP, and 2-Met-Thio ATP dilate the hindlimb vascular
      bed by a direct cAMP-dependent mechanism, and that the release of nitric oxide,
      vasodilator prostaglandins, K+(ATP) channel opening, or an inhibitory effect on
      the adrenergic nervous system play little, if any, role in mediating or
      modulating responses to the purinergic agonists in the hindlimb circulation of
      the cat.

PMID- 10958163
TI  - Canadian recommendations underestimate energy needs of women over fifty years as
      determined by doubly-labelled water.
AB  - Accurate estimations of energy requirements at the population level are crucial
      because of disease processes associated with energy imbalance. The present
      objective was to compare energy expenditure with existing Recommended Nutrient
      Intakes for Canadians (RNIC) and determine whether the RNIC provides a true index
      of energy requirement in middle-aged and elderly Canadian women. A second
      objective was to compare energy expenditure and the RNIC to Food and Agriculture
      Organization, World Health Organization, United Nations University (FAO/WHO/UNU)
      predictions. Seventy-six women were recruited for the study (67.3 +/- 11.5 y, 63
      +/- 11.7 kg, BMI 24.8 +/- 4.4 kg x m(-2)). The two-point doubly-labelled water
      (DLW) method was used over 13 days to assess energy expenditure while subjects
      carried out their routine activities. Subjects were stratified to enable age
      specific requirements for middle-aged and elderly women. At weight maintenance,
      energy needs were underestimated using the RNIC (7.1 +/- 1.6 MJ x d(-1), 1698 +/-
      391 kcal x d(-1)) compared to total energy expenditure (10.0 +/- 3.2 MJ x d(-1),
      2395 +/- 746 kcal x d(-1)) as determined by DLW as a whole and for each age
      group. The RNIC recommendations were lower than the FAO/WHO/UNU estimations even
      for light activity. Results indicate that mean energy expenditure was 29% greater
      than the RNIC recommendations created using formulas based on age and weight,
      whereas the FAO/WHO/ UNU estimations closely approximated energy expenditure
      based on heavy activity in women 49-79 y and light activity in women over 80 y
      old. These data suggest a systematic underestimation of Canadian energy
      recommendations for women.

PMID- 10958164
TI  - Interaction of vasomotor and exocrine neurons in bullfrog paravertebral
      sympathetic ganglia.
AB  - A 2 min sample of an intracellular recording of in vivo synaptic activity from a
      vasomotor C-neuron in a bullfrog sympathetic ganglion was converted to a series
      of stimulus pulses. This physiologically derived activity was used to stimulate
      preganglionic C-fibres of similar ganglia studied in vitro. Intracellular
      recordings were made from exocrine B-cells within the ganglia. Although they do
      not receive fast, nicotinic synaptic input from preganglionic C-fibres, B-cell
      excitability was profoundly increased by stimulation of C-fibres with
      physiologically derived activity. Also, subthreshold depolarizing current pulses
      that failed to generate action potentials in B-cells under control conditions
      almost always generated action potentials whilst C-fibres were activated. These
      effects were attenuated or prevented by the luteinizing hormone releasing hormone
      antagonist, [D-pyro-Glu1,D-Phe2,D-Trp3,6]-LHRH (70 microM). The physiological
      release of luteinizing hormone releasing hormone from C-fibres therefore causes
      an interaction between vasomotor and exocrine outflow within a paravertebral
      sympathetic ganglion.

PMID- 10958165
TI  - The suppression of potassium cyanide-induced mortality by the increase of
      extracellular acetylcholine level in the brain.
AB  - We examined whether potassium cyanide (KCN)-induced mortality in mice was
      regulated by acetylcholine transmission in the brain. Our novel compound, (+/-)-1
      (1,2-diphenyl)ethyl-4-[2-(3,4-dimethoxyphenyl)ethyl]piperazine dihydrochloride
      (SA3251), suppressed KCN-induced mortality in mice. In parallel, SA3251 increased
      the cortical and hippocampal extracellular acetylcholine level in conscious,
      freely-moving rats. Interestingly, the time course patterns of these two events
      induced by SA3251 correlated. These results suggest that the central cholinergic
      system plays an important role in the suppression of KCN-induced mortality.

PMID- 10958166
TI  - Effects of (+) and (-) enantiomers of calcium channel agonist, Bay K 8644, on
      mechanical and electrical responses of frog skeletal muscle.
AB  - The effects of (+) and (-) enantiomers of Bay K 8644, a Ca2+ channel agonist, on
      the mechanical and electrical properties of frog skeletal muscle fibers were
      investigated. In the concentration range of 10(-6) to 10(-5) M, both (+) and (-)
      enantiomers of Bay K 8644 significantly increased the maximum amplitudes of
      twitch responses. Both (+) and (-) enantiomers of Bay K 8644, at higher
      concentrations such as 10(-4) M, greatly depressed the amplitudes of twitches.
      Potentiating and depressing effects of (-) enantiomer of Bay K 8644 on twitch
      responses were significantly greater than those of the (+) enantiomer. At all
      concentrations used, both (+) and (-) enantiomers of Bay K 8644 significantly
      decreased the area under the tetanic force x time curve. In intracellular
      recordings, it was found that the depressing effects of both (+) and (-)-Bay K
      8644 on tetanic contractions and twitch responses were due to the inhibition of
      action potentials. The inhibitory effect of (-) enantiomer of Bay K 8644 on
      action potentials also was significantly greater than that of the (+) enantiomer.
      In conclusion, present results suggest that, in contrast with cardiac muscle
      fibers, (+) and (-) enantiomers of Bay K 8644 have similar inhibitory effects on
      the electrical and mechanical properties of frog skeletal muscle fibers.

PMID- 10958167
TI  - Myofibrillar disruption following acute concentric and eccentric resistance
      exercise in strength-trained men.
AB  - We have previously quantified the extent of myofibrillar disruption which occurs
      following an acute bout of resistance exercise in untrained men, however the
      response of well-trained subjects is not known. We therefore recruited six
      strength-trained men, who ceased training for 5 days and then performed 8 sets of
      8 uni-lateral repetitions, using a load equivalent to 80% of their concentric
      (Con) 1-repetition maximum. One arm performed only Con actions by lifting the
      weight and the other arm performed only eccentric actions (Ecc) by lowering it.
      Needle biopsy samples were obtained from biceps brachii of each arm approximately
      21 h following exercise, and at baseline (i.e., after 5 days without training),
      and subsequently analyzed using electron microscopy to quantify myofibrillar
      disruption. A greater (P < or = 0.05) proportion of disrupted fibres was found in
      the Ecc arm (45 +/- 11%) compared with baseline values (4 +/- 2%), whereas fibre
      disruption in the Con arm (27 +/- 4%) was not different (P > 0.05) from baseline
      values. The proportion of disrupted fibres and the magnitude of disruption
      (quantified by sarcomere counting) was considerably less severe than previously
      observed in untrained subjects after an identical exercise bout. Mixed muscle
      protein synthesis, assessed from approximately 21-29 h post-exercise, was not
      different between the Con- and Ecc-exercised arms. We conclude that the Ecc phase
      of resistance exercise is most disruptive to skeletal muscle and that training
      attenuates the severity of this effect. Moreover, it appears that fibre
      disruption induced by habitual weightlifting exercise is essentially repaired
      after 5 days of inactivity in trained men.

PMID- 10958168
TI  - External anions and volume-sensitive anion current in guinea-pig ventricular
      myocytes.
AB  - The objective of this study was to determine the effects of anion replacement on
      volume-sensitive anion current in guinea-pig ventricular myocytes. Myocytes in
      the conventional whole-cell voltage-clamp configuration were superfused and
      dialysed with Na(+)-, K(+)-, and Ca(2+)-free solution, and exposed to external 75
      mM Cl- solution of one-half normal osmolality. Prolonged exposures to hyposmotic
      solution promoted the development of outwardly-rectifying currents that were
      inactivated at high positive potentials and reversed in a Cl(-)-dependent manner
      (50 mV per decade pipette Cl- concentration). Replacement of external Cl- by
      iodide and aspartate affected the reversal potential (E(rev)) and slope
      conductance of the volume-sensitive current. Relative permeabilities calculated
      from changes in E(rev) were 1.49 +/- 0.09, 1.00, and 0.29 +/- 0.04 for iodide, Cl
      , and aspartate, respectively; relative slope conductances between E(rev) and
      E(rev) + 40 mV were 1.21 +/- 0.09, 1.00, and 0.43 +/- 0.07, respectively.
      Replacement of Cl- also affected the time dependence of the volume-sensitive
      current; replacement by iodide reversibly enhanced the decay of outward current
      at positive potentials, whereas replacement by aspartate reduced it. These
      results are compared with earlier findings on noncardiac time- and voltage
      dependent anion current activated by hyposmotic solution.

PMID- 10958169
TI  - Age- and myopathy-dependent changes in connexins of normal and cardiomyopathic
      Syrian hamster ventricular myocardium.
AB  - The conduction of cardiac action potentials depends on the flow of excitation
      through gap junctions, which are hexameric protein associations of connexins
      (Cxs). The major Cx reported in the heart is Cx43, although some Cx40 and Cx45
      are also present. There is some evidence for altered Cx content in heart failure.
      In heart failure, conduction is depressed and slowed conduction may contribute to
      arrhythmogenesis and (or) the maintenance of arrhythmia. Cx content and
      distribution were determined in ventricular tissues from normal and
      cardiomyopathic Syrian hamsters, an animal model of heart failure which has
      reproducible age-specific cardiomyopathy resulting in heart failure and age
      matched controls in three groups: young (3-5 weeks), adult (13-18 weeks), and old
      (>45 weeks). Frozen, unfixed sections of ventricular tissues were
      immunofluorescently stained using antibodies against Cx43, Cx40, and Cx45. Cx43
      was the predominant Cx detected in all samples. In normal hamsters, Cx43 was
      localized predominantly at the intercalated disc region, while in myopathic
      myocytes, it was scattered. In Western blots, Cx43 content of normal hamster
      hearts was highest in the adult hearts compared with young and old hamster
      hearts. In contrast, Cx43 content was significantly lower in adult
      cardiomyopathic hamster hearts compared with all other groups. The alterations of
      content and distribution of gap junction Cx43 may contribute to diminished
      conduction, pump function, and arrhythmogenesis in heart failure.

PMID- 10958170
TI  - Islet protein expression changes during diabetes development in islet syngrafts
      in BB-DP rats and during rejection of BB-DP islet allografts.
AB  - Interleukin 1beta (IL-1) is cytotoxic to rat pancreatic beta-cells in vitro, and
      increased expression of IL-1 mRNA is found in the islets of Langerhans during
      development of diabetes in BB/Wor/Mol-BB2 (BB-DP) rats and NOD mice. It has been
      proposed that IL-1 induces a race between protective and deleterious proteins in
      the beta-cells during development of diabetes, and that heat shock proteins 70
      and 90, and manganese superoxide dismutase, all inducible by IL-1 are potentially
      protective proteins. We have established a database of approximately 2000
      neonatal rat-islet proteins by two-dimensional gel (2-D gel) electrophoresis of
      [35S]-methionine labelled neonatal Wistar Furth rat islets. In these IL-1 was
      shown to up- or down-regulate the islet-expression level of 99, and to induce de
      novo synthesis of 6 proteins. The identity of most of the IL-1 induced proteins
      is unknown and under study. In this study we wished to investigate if changes in
      protein expression induced in vitro by IL-1 stimulation of islets are also seen
      in vivo during spontaneous development of diabetes in BB-DP rats, and during
      islet allograft rejection. Two-hundred neonatal BB-DP rat islets were grafted
      under the kidney capsule of either 30-day-old BB-DP rats killed at onset of
      diabetes or of 30-day-old Wistar Kyoto (WK) rats, killed 12 days after grafting.
      Proteins in excised islet-grafts and in vitro IL-1 exposed isolated neonatal BB
      DP rat islets were labelled with [35S]-methionine, and processed for 2-D gel
      electrophoresis. Fluorographs of the gels were analysed by computer. A total of
      1815 proteins were found in 3 of 3 12.5% polyacrylamide gels. Interleukin-1 was
      found to change expression level of 82 of these proteins (22 up- and 60 down
      regulated) in neonatal BB-DP rat islets in vitro. Of these 82 proteins 33 (4 up-
      and 29 down-regulated) also changed level of expression during disease occurrence
      in syngeneic islet grafts from diabetic BB-DP rats, and 29 (4 up- and 25 down
      regulated) during rejection of BB-DP islets grafted to WK rats. Changes in the
      expression level of 14 (3 up- and 11 down-regulated) of the 82 proteins altered
      by IL-1 in vitro were only found in syngeneic islet grafts in diabetic BB-DP
      rats, and changes in the expression level of 8 (2 up- and 6 down-regulated) of
      these 82 proteins expression were only found in BB-DP islet allografts in WK
      recipients. Identification of these proteins may be important in understanding
      the mechanisms of islet destruction during development of insulin-dependent
      diabetes mellitus and during islet allograft rejection.

PMID- 10958172
TI  - Relapsing arthritis induced by cell transfer from collagen-immunised mice.
AB  - Collagen-induced arthritis is a well-established model of chronic inflammatory
      arthritis. We here introduce a development of this model which combines the
      benefits of adoptive transfer and sequential relapse. DBA/1 x B10.Q F1 hybrid
      mice were immunised with bovine type II collagen, and those which developed a
      sufficiently high level of arthritis served as donors of spleen cells transferred
      into BALB/c SCID hosts. After boosting with 500 microg collagen, the development
      of host arthritis was monitored over a period of up to 256 days, during which up
      to three successive peaks were detected. In comparison with bovine collagen,
      mouse collagen used for boosting induced a lower initial peak but higher
      relapses. As expected, the transferred disease was more uniform than the freshly
      induced one. Previous information suggests that a shifting cytokine balance
      between protective and aggressive T cells may account for the relapse and
      remission. This study provides a model of relapsing polyarthritis, obtained with
      normal immunocytes boosted with a well-defined protein antigen in animals not
      themselves treated with adjuvant. As such it is relevant to the etiology of
      inflammatory arthritis in man, and, if further developed, could be of value for
      testing new therapeutic strategies.

PMID- 10958171
TI  - Time clustering of high titre insulin autoantibodies (IAA) in the cord blood of
      infants born to non-diabetic mothers.
AB  - Insulin autoantibodies (IAA) are markers for autoimmune insulitis, and are
      reported in up to 100% of diabetic children before the age of five years, but in
      fewer than 1% of their controls. Their origins are unknown. In this report a
      cluster of high titre IAA in cord blood is reported, distinct from the low titre
      'non-specific' binding previously described. The distributions of displaceable
      insulin binding measured in adults (Group A, n = 79), adolescents (Group B, n =
      19), primary school children (Group C, n = 32) and third trimester pregnant women
      (Group D, n = 60) were all unimodal, normal and not different from each other (A
      = 0.57+/-0.64%, B = 0.87+/-0.45%, C = 0.81+/-0.87% and D = 0.35+/-0.48%). The
      distribution of insulin binding in the cord sera of consecutive newborns (n =
      428) born between October and the following May, however, was bimodal. The first
      distribution, included 400 sera, was symmetrical and not different (0.79+/-0.45%)
      from groups A, B, C and D. The second distribution comprised the remaining 28
      sera (7% of the total sample) with insulin-displaceable binding values in an IDW
      validated radio assay ranging from 2.2% to 31.1%. The appearance of IAA was not
      HLA-restricted, but the frequency of IAA+ samples was seen to vary over five
      consecutive months. The timing is consistent with acute viral infection, but the
      implications for future insulin dependent diabetes will await long-term follow-up
      of the children and mothers involved.

PMID- 10958173
TI  - Serum anti-S100b, anti-GFAP and anti-NGF autoantibodies of IgG class in healthy
      persons and patients with mental and neurological disorders.
AB  - Natural autoantibodies of IgG class to proteins S100b, glial fibrillar acidic
      protein (GFAP), and nerve growth factor (NGF) are presented in serum of healthy
      adults and those levels/affinities are relatively constant and may vary among
      individuals within narrow limits. In patients with depressive disorder, epilepsy,
      multiple sclerosis, and Parkinson's disease dispersion of such autoantibodies
      serum levels were often found beyond the normal ranges. Most of the patient
      groups include cases with significantly elevated as well as abnormally decreased
      immunoreactivity parameters. This leads us to assumption that changes in some
      basic mechanisms of individual immune state represent the common features of
      different forms of pathology of the nervous system.

PMID- 10958174
TI  - Effect of anti-beta2glycoprotein I Lupus Anticoagulants on fibrin polymerization
      and fibrinolysis.
AB  - Anti-beta2-Glycoprotein I (beta2GPI) autoantibodies are the prominent laboratory
      feature of Hughes syndrome. By prolonging some coagulation tests in the presence
      of exogenous phospholipids (PL), they behave as classical Lupus Anticoagulants
      (LA). We investigated the effect of 3 affinity-purified anti-beta2GPI IgG
      preparations from patients with Hughes syndrome on fibrin polymerization and
      fibrinolysis of normal plasma, measured by comparing the optical densities of
      assay mixtures in the presence of the autoantibodies or normal IgG. The presence
      of anti-beta2GPI IgG in diluted Russell Viper Venom Time (dRVVT) assays, carried
      out using a PL dilution of 1:8 or 1:64, resulted in a delay in the onset of
      polymerization by 30-40 and 60-70s, respectively. Fibrin polymerization was
      complete after 250s for both anti-beta2GPI IgG and normal IgG. The inhibitory
      effect of the anti-beta2GPI antibodies was not observed in the presence of excess
      PL, as expected for LA. Anti-beta2GPI IgG increased the plateau level of
      polymerization when dRVVT was performed in the presence of 1.5 nM recombinant
      tissue plasminogen activator, but did not impair the fibrinolytic process, which
      was almost complete after 250 min. The autoantibodies did not delay the onset of
      fibrin polymerization in tests carried out using recombinant tissue factor. On
      the contrary, the autoantibodies enhanced polymerization in prothrombin time
      assays, and accelerated it in tissue thromboplastin inhibition tests, with no
      effect on fibrinolysis. These data provide evidence that anti-beta2GPI LA may act
      as either anticoagulants or procoagulants in different in vitro coagulation
      tests.

PMID- 10958175
TI  - T cells of mice treated with mPEG-myasthenogenic peptide conjugate are involved
      in protection against EAMG by stimulating lower pathogenic antibody responses.
AB  - Experimental autoimmune myasthenia gravis (EAMG) can be induced in C57BL/6 (B6)
      mice by immunization with Torpedo californica acetylcholine receptor (tAChR). We
      had previously shown that pretreatment with a monomethoxypolyethylene glycol
      (mPEG) conjugate of myasthenogenic tAChR alpha-chain peptide alpha125-148 (mPEG
      peptide) suppressed EAMG. In order to understand the mechanism involving T cells
      in the induction of this suppression, we have studied, in the present work, the
      in vitro responses of T cells from mPEG-peptide treated B6 mice after an initial
      tAChR injection to determine the early effect of mPEG-peptide treatment on these
      responses. Treatment with mPEG-peptide reduced the T cell responses to tAChR and
      several tAChR alpha-chain peptides. To further investigate the T cell helper
      function in vivo, we transferred T cells from B6 mice that received either mPEG
      peptide or control PBS followed by two tAChR injections to non-immune B6 mice. T
      cell transfer from mPEG-peptide pretreated mice down regulated, in recipient
      mice, Ab induction (after cell transfer) and Ab production (after two tAChR
      injections) toward alpha-chain peptides. Treatment of B6 mice with mPEG-peptide
      did not alter the ability of their APC to present peptide alpha146-162 to peptide
      specific B6 T cells. The results indicate that suppression of EAMG by treatment
      with mPEG-peptide is due to T cell involvement and not to a defect in APC
      function.

PMID- 10958176
TI  - Evidence for humoral and cellular reactivity against keratin and thyroglobulin in
      HTLV-I infected rabbits.
AB  - Human T cell leukemia virus type I (HTLV-I) infection was initially associated
      with T cell leukemia and a progressive neurologic disease but has since been
      linked to an increasing number of autoimmune disorders, including Sjogren's
      syndrome, uveitis, and polyarthritis. A survey of serum samples from a rabbit
      model of HTLV-I infection revealed that all had antibodies against keratin and
      thyroglobulin. Sera from several infected rabbits also reacted with collagen,
      while antibody reactions with other autoantigens tested, including DNA, were rare
      and sporadic. In addition to antibodies, cellular reactivity to keratin, but not
      thyroglobulin, was demonstrated by cellular proliferation in presence of IL-2 and
      keratin. Expanded cell cultures were positive for T cell activation markers and
      CD8. Association of the auto-reactivity with HTLV-I infection rather than random
      anti-cellular responses was supported by the fact that no antikeratin or
      antithyroglobulin was seen in uninfected controls, including that inoculated with
      uninfected lymphocytes. Finding autoantibodies in rabbits infected using naked
      HTLV-I DNA clones provided further assurance that infection induced the
      autoimmune reactions detected.

PMID- 10958177
TI  - Disproportion of helper T cell subsets in peripheral blood of patients with
      primary Sjogren's syndrome.
AB  - We studied the proportions of Th1 and Th2 cells in peripheral blood of 15
      patients with primary Sjogren's syndrome (p-SS), by using a procedure to
      enumerate the cells synthesizing cytokines such as INF-gamma or IL-4 in cytoplasm
      of CD4+ lymphocytes. The frequency of Th1 (INF-gamma containing) cells in p-SS
      patients was significantly reduced as compared to normal control (20.57+/-7.48%
      vs 28.78+/-11.56%, p < 0.05), while that of Th2 (IL-4 containing) cells was not
      different from normal control (3.33+/-0.98% vs 2.85+/-1.88%). The ratio of Th1 to
      Th2 cells in p-SS patients was significantly decreased as compared to normal
      control (6.60+/-3.15 vs 11.55+/-6.72, p < 0.05). There was no difference in
      frequency of Th1 or of Th2 cells between 8 patients given small amounts of
      prednisolone (PSL) and 7 patients not given PSL (21.44+/-9.39% vs 19.57+/-5.05%,
      3.12+/-0.80% vs 3.56+/-1.17%). The percentage of Th1 cells was not different
      between 7 patients with glandular symptoms (G) and 8 patients with extraglandular
      symptoms (EG) (18.61+/-9.63% vs 22.27+/-5.02%). Although the frequency of Th2
      cells was higher in EG-patients than that in G-patients (3.84+/-0.78% vs 2.74+/
      0.86%) with tendency of elevated IgG level in sera, the ratio of Th1 to Th2 cells
      was not different among them (6.26+/-2.84 vs 6.99+/-3.64). These results suggest
      that the reduced ratio of Th1 to Th2 cells is essential and is related to the
      dysfunction of cellular immunity in p-SS.

PMID- 10958178
TI  - Prevention of diabetes mellitus in the non-obese diabetic mouse strain with
      monoclonal antibodies against the CD45RB molecule.

PMID- 10958179
TI  - The measurement of diffusion and perfusion in biological systems using magnetic
      resonance imaging.
AB  - The aim of this review is to describe two recent developments in the use of
      magnetic resonance imaging (MRI) in the study of biological systems: diffusion
      and perfusion MRI. Diffusion MRI measures the molecular mobility of water in
      tissue, while perfusion MRI measures the rate at which blood is delivered to
      tissue. Therefore, both these techniques measure quantities which have direct
      physiological relevance. It is shown that diffusion in biological systems is a
      complex phenomenon, influenced directly by tissue microstructure, and that its
      measurement can provide a large amount of information about the organization of
      this structure in normal and diseased tissue. Perfusion reflects the delivery of
      essential nutrients to tissue, and so is directly related to its status. The
      concepts behind the techniques are explained, and the theoretical models that are
      used to convert MRI data to quantitative physical parameters are outlined.
      Examples of current applications of diffusion and perfusion MRI are given. In
      particular, the use of the techniques to study the pathophysiology of cerebral
      ischaemia/stroke is described. It is hoped that the biophysical insights provided
      by this approach will help to define the mechanisms of cell damage and allow
      evaluation of therapies aimed at reducing this damage.

PMID- 10958180
TI  - Thresholds for visual detection of Young's modulus contrast in simulated
      ultrasound image movies.
AB  - Elasticity imaging (EI) is being developed to allow the evaluation of the
      mechanical properties of soft tissue, but these properties are already assessed
      in routine ultrasound breast examination using a method that involves the
      subjective interpretation of tissue motion seen in real-time B-mode image movies
      during palpation. We refer to this method as relative motion assessment (RMA).
      The purpose of this study was to begin a process of learning about the usefulness
      and limitations of RMA relative to the emerging method of elasticity imaging.
      Perception experiments were performed to measure Young's modulus contrast
      thresholds for positive contrast lesions under controlled conditions that could
      subsequently be repeated to evaluate elasticity imaging for the same task.
      Observer ability to grade relative lesion contrast using RMA was also assessed.
      Simulated sequences of B-scans of tissue moving in response to an applied force
      were generated and used in a two-alternative forced-choice (2-AFC) experiment to
      measure contrast thresholds for the detection of disc-shaped elastic lesions by
      RMA in the absence of ultrasound echo contrast. Results were obtained for four
      observers at a lesion area of about 77 speckle cells and for five observers at
      lesion areas of about 42 and 139 speckle cells. Young's modulus contrast
      thresholds were found to decrease with increasing lesion size and were well
      within the range of contrast values that have been measured for breast tumours in
      vitro. It was also found that observers were quite skilled at using RMA to grade
      the relative strain contrast of lesions. The nonlinear relationship between the
      object contrast (Young's modulus contrast) and the image contrast (strain
      contrast) prevented observers from detecting very small lesions with 100%
      accuracy, no matter how high the object contrast. A preliminary comparison of the
      results for RMA with published thresholds for elastography indicated that
      elastography is likely to offer great benefit in reducing modulus contrast
      thresholds, but further study is required to confirm this.

PMID- 10958181
TI  - Two-dimensional MR elastography with linear inversion reconstruction: methodology
      and noise analysis.
AB  - A methodology for imposing approximate plane strain conditions in magnetic
      resonance elastography through physical constraint is described. Under plane
      strain conditions, data acquisition and analysis may be conducted in two
      dimensions, which reduces imaging and reconstruction time significantly compared
      with three-dimensional analysis. Simulations and experiments are performed to
      illustrate the constraint concept. A signal/noise analysis of a two-dimensional
      linear inversion technique for relative elastic modulus is undertaken, and
      modifications to the numerical method are described which can reduce the SNR
      requirements by a factor of two to four. Experimentally measured data are
      reconstructed to illustrate the performance of the method.

PMID- 10958182
TI  - The effect of respiratory motion on CSI localized MRS. Cooperative Group on MR
      Applications to Cancer.
AB  - A theoretical model to assess the effect of respiratory motion on chemical shift
      imaging (CSI) data of an extended sample is described. Data from the model are
      shown to agree with those acquired experimentally from phantoms. In CSI, Fourier
      bleed and ghost artefacts are of particular significance when the tissue of
      interest is adjacent to other tissue with much higher concentrations of
      metabolites, such as chest wall muscle adjacent to breast tumour tissue. We have
      evaluated contamination due to Fourier bleed and ghosting due to subject motion
      separately. The results demonstrate that the amount of signal contamination due
      to motion is relatively independent of the ratio of sample width to voxel width
      and of the period of motion, but has a strong dependence on the number of phase
      encoding steps and the amplitude of the motion.

PMID- 10958183
TI  - Implications of respiratory motion for the quantification of 2D MR spectroscopic
      imaging data in the abdomen.
AB  - Magnetic resonance spectroscopic imaging (MRSI) studies in the abdomen or breast
      are acquired in the presence of respiratory motion. This modifies the point
      spread function (PSF) and hence the reconstructed spectra. We evaluated the
      quantitative effects of both periodic and aperiodic motion on spectra localized
      by MRSI. Artefactual signal changes, both the modification of native to a voxel
      and spurious signals arising elsewhere, depend primarily upon the motion
      amplitude relative to the voxel dimension. A similar dependence on motion
      amplitude was observed for simple harmonic motion (SHM), quasi-periodic motion
      and random displacements. No systematic dependence upon the period or initial
      phase of SHM or on the array size was found. There was also no significant
      variation with motion direction relative to the internal and external phase
      encoding directions. In measured excursion ranges of 20 breast and abdominal
      tumours, 70% moved < or = 5 mm, while 30% moved 6-23 mm. The diaphragm and fatty
      tissues in the gut typically moved approximately 15-20 mm. While tumour/organ
      excursions less than half the voxel dimension do not substantially affect native
      signals, the bleeding in of strong lipid signals will be problematic in 1H
      studies. MRSI studies in the abdomen, even of relatively well-anchored tumours,
      are thus likely to benefit from the addition of respiratory triggering or other
      motion compensation strategies.

PMID- 10958184
TI  - Radiotherapy planning of the pelvis using distortion corrected MR images: the
      removal of system distortions.
AB  - Image distortion is an important consideration in the use of magnetic resonance
      (MR) images for radiotherapy planning. The distortion is a consequence of system
      distortion (arising from main magnetic field inhomogeneity and nonlinearities in
      the applied magnetic field gradients) and of effects arising from the
      object/patient being imaged. A two stage protocol has been developed to correct
      both system and object-induced distortion in pelvic images which incorporates
      measures to maintain the quality, accuracy and consistency of the imaging and
      correction procedures. The first stage of the correction procedure is described
      here and involves the removal of system distortion. Object- (patient-) induced
      effects will be described in a subsequent work. Images are acquired with the
      patient lying on a flat rigid bed, which reproduces treatment conditions. A frame
      of marker tubes surrounding the patient and attached to the bed provides quality
      assurance data in each image. System distortions in the three orthogonal planes
      are mapped using a separate phantom, which fits closely within the quality
      control frame. Software has been written which automates the measurement and
      checking of the many marker positions which the test objects generate and which
      ensures that patient data are acquired using a consistent imaging protocol.
      Results are presented which show that the scanner and the phantoms used in
      measuring distortion give highly reproducible results with mean changes of the
      order of 0.1 mm between repeated measurements of marker positions in the same
      imaging session. Effective correction for in plane components of system
      distortion is demonstrated.

PMID- 10958185
TI  - Constrained treatment planning using sequential beam selection.
AB  - In this paper an algorithm is described for automated treatment plan generation.
      The algorithm aims at delivery of the prescribed dose to the target volume
      without violation of constraints for target, organs at risk and the surrounding
      normal tissue. Pre-calculated dose distributions for all candidate orientations
      are used as input. Treatment beams are selected in a sequential way. A score
      function designed for beam selection is used for the simultaneous selection of
      beam orientations and weights. In order to determine the optimum choice for the
      orientation and the corresponding weight of each new beam, the score function is
      first redefined to account for the dose distribution of the previously selected
      beams. Addition of more beams to the plan is stopped when the target dose is
      reached or when no additional dose can be delivered without violating a
      constraint. In the latter case the score function is modified by importance
      factor changes to enforce better sparing of the organ with the limiting
      constraint and the algorithm is run again.

PMID- 10958186
TI  - Removing the effect of statistical uncertainty on dose-volume histograms from
      Monte Carlo dose calculations.
AB  - Dose-volume histograms (DVHs) of the dose distributions calculated by the Monte
      Carlo method contain statistical uncertainties. The Monte Carlo DVH can be
      considered as blurred from the noiseless DVH by the statistical uncertainty. The
      focus of the present work is on the removal of the statistical uncertainty effect
      on the Monte Carlo DVHs and the reconstruction of the noiseless DVHs. We first
      study the effect of statistical uncertainty. It is found that the steeper the
      DVH, the more significant the effect. For typical critical structure DVHs the
      effect is usually negligible. For the target DVHs the effect could be clinically
      significant, depending on the value of uncertainty and the slope of the DVH. We
      then propose an iterative reconstruction algorithm. Using the DVHs and
      statistical uncertainties from the Monte Carlo simulations, we are able to
      reconstruct the noiseless DVHs. A hypothetical example and a number of clinical
      cases have been used to test the proposed algorithm. For each clinical case, two
      Monte Carlo simulations (denoted A and B) were performed. Simulation A has very
      large statistical uncertainties (about 10% of dose in the target volume) while
      simulation B has very small uncertainties (about 1%). DVHs from simulation B were
      used to approximate the noiseless DVHs. Using the proposed algorithm, the effect
      of statistical uncertainty can be removed from the DVHs of simulation A. The
      reconstructed DVHs were in good agreement with the DVHs from simulation B. The
      proposed approach is expected to be useful in removing the blurring effect on a
      quickly calculated Monte Carlo DVH when performing the iterative forward
      treatment planning.

PMID- 10958187
TI  - Investigation of variance reduction techniques for Monte Carlo photon dose
      calculation using XVMC.
AB  - Several variance reduction techniques, such as photon splitting, electron history
      repetition, Russian roulette and the use of quasi-random numbers are investigated
      and shown to significantly improve the efficiency of the recently developed XVMC
      Monte Carlo code for photon beams in radiation therapy. It is demonstrated that
      it is possible to further improve the efficiency by optimizing transpon
      parameters such as electron energy cut-off, maximum electron energy step size,
      photon energy cut-off and a cut-off for kerma approximation, without loss of
      calculation accuracy. These methods increase the efficiency by a factor of up to
      10 compared with the initial XVMC ray-tracing technique or a factor of 50 to 80
      compared with EGS4/PRESTA. Therefore, a common treatment plan (6 MV photons, 10 x
      10 cm2 field size, 5 mm voxel resolution, 1% statistical uncertainty) can be
      calculated within 7 min using a single CPU 500 MHz personal computer. If the
      requirement on the statistical uncertainty is relaxed to 2%, the calculation time
      will be less than 2 min. In addition, a technique is presented which allows for
      the quantitative comparison of Monte Carlo calculated dose distributions and the
      separation of systematic and statistical errors. Employing this technique it is
      shown that XVMC calculations agree with EGSnrc on a sub-per cent level for
      simulations in the energy and material range of interest for radiation therapy.

PMID- 10958188
TI  - Intensity modulated arc therapy (IMAT) with centrally blocked rotational fields.
AB  - A new technique for intensity-modulated beam (IMB) delivery that combines the
      features of intensity modulated arc therapy (IMAT) with the use of 'classical
      blocks' is proposed. The role of the blocks is to realize the high-gradient
      modulation of the intensity profile corresponding to the region to be protected
      within the body contour, while the MLC leaves or the secondary collimator defines
      the rest of the field and delivers intensity-modulated multiple rotational
      segments. The centrally blocked radiation fields are applied sequentially, in
      several rotations. Each rotation of the gantry is responsible for delivering one
      segment of the optimal intensity profile. The new IMAT technique is applied for a
      treatment geometry represented by an annular target volume centrally located
      within a circular body contour. The annulus encompasses a circular critical
      structure, which is to be protected. The beam opening and corresponding weight of
      each segment are determined in two ways. The first method applies a linear
      optimization algorithm to precalculated centrally blocked radial dose profiles.
      These radial profiles are calculated for a set of beam openings, ranging from the
      largest field that covers the whole planning target volume (PTV) to the smallest,
      which is 1 cm larger than the width of the central block. The optimization is
      subjected to dose homogeneity constraints imposed on a linear combination of
      these profiles and finally delivers the dimensions and weights of the rotational
      beams to be used in combination. The second method decomposes into several
      subfields the fluence profile of a rotational beam known to deliver a constant
      dose level to PTV. This fluence profile is determined by using the analytical
      method proposed by Brahme for the case of the annular PTV and the concentric
      organ at risk (OAR). The proper segmentation of this intensity profile provides
      the field sizes and corresponding weights of the subfields to be used in
      combination. Both methods show that for this particular treatment geometry, three
      to seven segments are sufficient to cover the PTV with the 95% dose level and to
      keep the dose level to the central critical structure under 30% of the maximum
      dose. These results were verified by experimentally delivering the calculated
      segments to radiotherapy verification films sandwiched between two cylindrical
      pieces of a pressed-wood phantom. The total beam time for a three-field
      irradiation was 77 s. The predicted and experimental dose profiles along the
      radius of the phantom agreed to within 5%. Generalization of this technique to
      real-patient treatment geometry and advantages over other conformal radiotherapy
      techniques are also discussed.

PMID- 10958189
TI  - A quality assurance device for the accuracy of the isocentres of teletherapy and
      simulation machines.
AB  - A new quality assurance device has been designed to measure the location and
      wobble of the radiation isocentre of linacs and simulation machines as a function
      of gantry rotation. The radiation isocentre is the intersection in space of the
      central x rays of a linac or simulation machine at different gantry angles. Six
      radio-opaque markers 1 mm in size are embedded in a radio-transparent calibration
      object (specifically, a hollowed cube) in such a way that the markers are non
      coplanar and uniquely identifiable in radiographic projections. The projective
      radiographs are obtained on the films held by the film holder attached to the
      gantry during the QA procedure. The marker positions of the calibration object
      define a known 3D reference frame, and their image positions on each radiograph
      determine the projective (3D to 2D matrix) transformation for that radiograph.
      Once the transformation is found, a 3D ray from the radiation source to any
      radiograph pixel becomes known. The radiographic pixels are coordinated
      (positioned and scaled) with respect to the projected image of radio-opaque
      fiducial cross-hairs fixed to a block tray and thus to the gantry. We select the
      central ray to correspond to the radiographic pixel whose rays at different
      gantry angles intersect in the smallest spatial domain. That pixel is found by a
      spiral search in the radiograph outward from the image of the radio-opaque cross
      hair intersection. The wobble of the isocentre is defined by the set of points
      (on the central rays) at closest approach to the isocentre. The device was tested
      and compared with commercially available QA devices. It is able to locate the
      isocentre to within 0.5 mm. The offset of this derived radiation isocentre from
      the intersection of the positioning lasers can be found. To do this, the
      calibration object is initially placed so that the laser intersection point falls
      on a seventh radio-opaque marker near the centre of the hollow cube calibration
      object. The seventh marker is embedded in a thin radio-transparent rod that
      diagonally spans the hollowed space.

PMID- 10958190
TI  - Verification of absolute dose rates for intravascular brachytherapy beta sources.
AB  - The absolute dose rate around beta sources for intravascular brachytherapy was
      measured with thin thermoluminescent (TL) dosimeters and radiochromic film. The
      calibration of these dosimeters was performed at the dose maximum in a 6 MeV
      electron beam of a linear accelerator. Compared to the values given by the
      manufacturers, higher dose rates of about 20% for 90Sr/90Y source trains and 20
      to 40% for 90Y line sources were found. We also measured the dose rate for a
      planar 90Sr/90Y source, which was calibrated at NIST (National Institute of
      Standards and Technology). This source serves as a reference for the
      determination of the dose rates by the supplier of the 90Y sources. For this
      source we measured a 13% higher dose rate compared to the value given in the
      calibration report by NIST. Our observation can have important consequences for
      the interpretation and comparison of the dose-related clinical results of
      intravascular brachytherapy with these and other beta sources. Also the
      comparison of the clinical results obtained with beta sources and gamma sources,
      i.e. 192Ir, depends largely on the accuracy of the absolute dosimetry of the beta
      sources.

PMID- 10958191
TI  - Electromagnetic and heat transfer computations for non-ionizing radiation
      dosimetry.
AB  - Reliable information on the heat distribution inside biological tissues is
      essential for the planning and optimization of experiments which aim to study the
      effects of non-ionizing radiation (NIR). In electrodynamics, the finite
      difference time-domain (FDTD) technique has become the dominant technique for
      radiofrequency dosimetry. In order to obtain the electromagnetic field and heat
      distributions within the same simulation run without changing discretization, a
      heat diffusion solver has been directly integrated into an advanced
      electrodynamic FDTD kernel. The implementation enables both coupled and
      sequential simulations. It also includes the ability to work with complex bodies
      and to accelerate heat diffusion. This paper emphasizes the importance of this
      combination in the field of NIR dosimetry. Two examples from this area are given:
      the validation of dosimetry with temperature probes and the estimation of the
      highest thermal load during bioexperiments.

PMID- 10958192
TI  - Home radon levels and seasonal correction factors for the Isle of Man.
AB  - Ionizing radiation dose levels due to home radon can rise to levels that would be
      illegal for workers in the nuclear industry. It is well known that radon levels
      within homes and from home to home, and also from month to month, vary
      considerably. To define an Isle of Man radon seasonal correction factor, readings
      were taken in eight homes over a 12 month period. An average island indoor
      exposure of 48 Bq m(-3) (range 4-518 Bq m(-3)) was determined from 285 homes
      selected from a cohort of 1300 families participating in the European
      Longitudinal Study of Pregnancy and Childhood (ELSPAC) in the Isle of Man. This
      compares with a UK home average of 20 Bq m(-3) and a European Union average
      (excluding UK) of 68 Bq m(-3). Ten homes of those measured were found to have
      radon levels above the National Radiological Protection Board 200 Bq m(-3) action
      level. There are 29,377 homes on the Isle of Man, suggesting that there could be
      some 900 or more homes above the action level. No statistical difference was
      found between the NRPB and Isle of Man seasonal correction factors.

PMID- 10958193
TI  - Evaluation of differences in ultraviolet exposure during weekend and weekday
      activities.
AB  - The weekday UV exposures to anatomical sites were evaluated for outdoor workers,
      home workers, adolescents, indoor workers, school staff and students in south
      east Queensland, Australia. Additionally, the UV exposures at weekends of school
      staff, school students, indoor workers and outdoor workers were evaluated. The
      weekday exposures per day ranged from 1.0 to 11.0 SED for winter to summer
      respectively. During spring, the ratios of the personal exposures divided by the
      ambient exposures at the weekend to the personal exposures divided by the ambient
      exposures on the weekdays to the neck, hand and left arm were at least 3.4, 2.0
      and 0.67 for the indoor workers, school staff and students and outdoor workers
      respectively. The same ratios for the erythemal UV exposures over the year,
      estimated from the exposures on four days in each of the four seasons, were at
      least 2.3 for the school staff and at least 1.3 for the 13 to 19 year old school
      students. These results reinforce the importance of targeting prevention
      programmes to both weekend and weekday exposures.

PMID- 10958194
TI  - DPM, a fast, accurate Monte Carlo code optimized for photon and electron
      radiotherapy treatment planning dose calculations.
AB  - A new Monte Carlo (MC) algorithm, the 'dose planning method' (DPM), and its
      associated computer program for simulating the transport of electrons and photons
      in radiotherapy class problems employing primary electron beams, is presented.
      DPM is intended to be a high accuracy MC alternative to the current generation of
      treatment planning codes which rely on analytical algorithms based on an
      approximate solution of the photon/electron Boltzmann transport equation. For
      primary electron beams, DPM is capable of computing 3D dose distributions (in 1
      mm3 voxels) which agree to within 1% in dose maximum with widely used and
      exhaustively benchmarked general-purpose public-domain MC codes in only a
      fraction of the CPU time. A representative problem, the simulation of 1 million
      10 MeV electrons impinging upon a water phantom of 128(3) voxels of 1 mm on a
      side, can be performed by DPM in roughly 3 min on a modern desktop workstation.
      DPM achieves this performance by employing transport mechanics and electron
      multiple scattering distribution functions which have been derived to permit long
      transport steps (of the order of 5 mm) which can cross heterogeneity boundaries.
      The underlying algorithm is a 'mixed' class simulation scheme, with differential
      cross sections for hard inelastic collisions and bremsstrahlung events described
      in an approximate manner to simplify their sampling. The continuous energy loss
      approximation is employed for energy losses below some predefined thresholds, and
      photon transport (including Compton, photoelectric absorption and pair
      production) is simulated in an analogue manner. The delta-scattering method
      (Woodcock tracking) is adopted to minimize the computational costs of
      transporting photons across voxels.

PMID- 10958195
TI  - Energy- and intensity-modulated electron beams for radiotherapy.
AB  - This work investigates the feasibility of optimizing energy- and intensity
      modulated electron beams for radiation therapy. A multileaf collimator (MLC)
      specially designed for modulated electron radiotherapy (MERT) was investigated
      both experimentally and by Monte Carlo simulations. An inverse-planning system
      based on Monte Carlo dose calculations was developed to optimize electron beam
      energy and intensity to achieve dose conformity for target volumes near the
      surface. The results showed that an MLC with 5 mm leaf widths could produce
      complex field shapes for MERT. Electron intra- and inter-leaf leakage had
      negligible effects on the dose distributions delivered with the MLC, even at
      shallow depths. Focused leaf ends reduced the electron scattering contributions
      to the dose compared with straight leaf ends. As anticipated, moving the MLC
      position toward the patient surface reduced the penumbra significantly. There
      were significant differences in the beamlet distributions calculated by an
      analytic 3-D pencil beam algorithm and the Monte Carlo method. The Monte Carlo
      calculated beamlet distributions were essential to the accuracy of the MERT dose
      distribution in cases involving large air gaps, oblique incidence and
      heterogeneous treatment targets (at the tissue-bone and bone-lung interfaces). To
      demonstrate the potential of MERT for target dose coverage and normal tissue
      sparing for treatment of superficial targets, treatment plans for a hypothetical
      treatment were compared using photon beams and MERT.

PMID- 10958196
TI  - High-resolution field shaping utilizing a masked multileaf collimator.
AB  - Multileaf collimators (MLCs) have become an important tool in the modern
      radiotherapy department. However, the current limit of resolution (1 cm at
      isocentre) can be too coarse for acceptable shielding of all fields. A number of
      mini- and micro-MLCs have been developed, with thinner leaves to achieve approved
      resolution. Currently however, such devices are limited to modest field sizes and
      stereotactic applications. This paper proposes a new method of high-resolution
      beam collimation by use of a tertiary grid collimator situated below the
      conventional MLC. The width of each slit in the grid is a submultiple of the MLC
      width. A composite shaped field is thus built up from a series of subfields, with
      the main MLC defining the length of each strip within each subfield. Presented
      here are initial findings using a prototype device. The beam uniformity
      achievable with such a device was examined by measuring transmission profiles
      through the grid using a diode. Profiles thus measured were then copied and
      superposed to generate composite beams, from which the uniformity achievable
      could be assessed. With the average dose across the profile normalized to 100%,
      hot spots up to 5.0% and troughs of 3% were identified for a composite beam of 2
      x 5.0 mm grids, as measured at Dmax for a 6 MV beam. For a beam composed from 4 x
      2.5 mm grids, the maximum across the profile was 3.0% above the average, and the
      minimum 2.5% below. Actual composite profiles were also formed using the
      integrating properties of film, with the subfield indexing performed using an
      engineering positioning stage. The beam uniformity for these fields compared well
      with that achieved in theory using the diode measurements. Finally sine wave
      patterns were generated to demonstrate the potential improvements in field
      shaping and conformity using this device as opposed to the conventional MLC
      alone. The scalloping effect on the field edge commonly seen on MLC fields was
      appreciably reduced by use of 2 x 5.0 mm grids, and still further by the use of 4
      x 2.5 mm grids, as would be expected. This was also achieved with a small or
      negligible broadening of the beam penumbra as measured at Dmax.

PMID- 10958197
TI  - On isocentre adjustment and quality control in linear accelerator based
      radiosurgery with circular collimators and room lasers.
AB  - We have developed a densitometric method for measuring the isocentric accuracy
      and the accuracy of marking the isocentre position for linear accelerator based
      radiosurgery with circular collimators and room lasers. Isocentric shots are used
      to determine the accuracy of marking the isocentre position with room lasers and
      star shots are used to determine the wobble of the gantry and table rotation
      movement, the effect of gantry sag, the stereotactic collimator alignment, and
      the minimal distance between gantry and table rotation axes. Since the method is
      based on densitometric measurements, beam spot stability is implicitly tested.
      The method developed is also suitable for quality assurance and has proved to be
      useful in optimizing isocentric accuracy. The method is simple to perform and
      only requires a film box and film scanner for instrumentation. Thus, the method
      has the potential to become widely available and may therefore be useful in
      standardizing the description of linear accelerator based radiosurgical systems.

PMID- 10958198
TI  - Evaluation of EGS4/PRESTA multiple-scattering algorithms for 90Sr/90Y
      intravascular brachytherapy dosimetry.
AB  - The purpose of this work is to evaluate the EGS4/PRESTA electron multiple
      scattering (MS) algorithms for dose calculation in intravascular brachytherapy
      (IVBT) using a 90Sr/90Y source. The small source size and the small volume of
      interest in IVBT require very fine spatial resolution, which may break down the
      constraints of Moliere's MS theory as implemented in EGS4. The theory is accurate
      only when the electron step sizes are large enough to allow the number of
      collisions omega0 to be much greater than e = 2.7183. When step sizes are too
      small to allow at least 2.7183 collisions, as may be necessitated by the fine
      geometry, the algorithm may switch off MS, producing dosimetric artefacts. This
      study showed that switching off MS could produce a dose deviation of up to 6%
      when the half-thickness (d/2) of the dose scoring region is comparable with the
      Moliere minimum step size (t(min) = 2.7183). The effect of switching off MS is
      negligible if d/2 >> t(min) For the case of omega0 > e, if the electron step
      sizes are chosen to allow five to 40 collisions, with increasing step size, the
      doses surrounding the source increase and the error decreases. On the other hand,
      when larger step sizes are chosen, the dose calculation voxel size must also be
      increased in order for the calculations to converge. A good compromise between
      accuracy and applicability for IVBT simulation can be made, if the thickness of
      the scoring region is 0.1 mm and the electron step sizes are in the range
      allowing 10 to 30 collisions.

PMID- 10958200
TI  - Thermal effects of radiation from cellular telephones.
AB  - A finite element thermal model of the head has been developed to calculate
      temperature rises generated in the brain by radiation from cellular telephones
      and similar electromagnetic devices. A 1 mm resolution MRI dataset was segmented
      semiautomatically, assigning each volume element to one of ten tissue types. A
      finite element mesh was then generated using a fully automatic tetrahedral mesh
      generator developed at NRPB. There are two sources of heat in the model: firstly
      the natural metabolic heat production; and secondly the power absorbed from the
      electromagnetic field. The SAR was derived from a finite difference time domain
      model of the head, coupled to a model 'mobile phone', namely a quarter-wavelength
      antenna mounted on a metal box. The steady-state temperature distribution was
      calculated using the standard Pennes 'bioheat equation'. In the normal cerebral
      cortex the high blood perfusion rate serves to provide an efficient cooling
      mechanism. In the case of equipment generally available to the public, the
      maximum temperature rise found in the brain was about 0.1 degrees C. These
      results will help in the further development of criteria for exposure guidelines,
      and the technique developed may be used to assess temperature rises associated
      with SARs for different types of RF exposure.

PMID- 10958199
TI  - Phantom materials for boron neutron capture therapy.
AB  - The aim of this work was to establish which reference phantom material is most
      suited for dosimetry under reference conditions of neutron beams for boron
      neutron capture therapy (BNCT). For this purpose, phantoms of dimensions 15 x 15
      x 15 cm3 and 30 x 30 x 30 cm3, composed of water, tissue-equivalent (TE) liquid,
      polyethylene (PE), polymethyl methacrylate (PMMA) and water containing 10 microg
      g(-1) and 30 microg g(-1) 10B were irradiated using the Petten BNCT beam.
      Activation foils and a diode detector were used for the determination of the
      thermal neutron fluence rate. The gamma-ray dose rate and the fast neutron dose
      rate were determined using paired ionization chambers. In water, PMMA and TE
      liquid the absolute dose and fluence values agreed within 3% at a reference depth
      of 2 cm, with the exception of the gamma-ray dose rate in PMMA, which was 12%
      lower than in water. Due to a higher hydrogen concentration in PE compared with
      water, the dose and fluence values in PE differed more than 30% from those in
      water. Only minor differences were observed between the percentage depth dose
      curves for the various dose components in water, PMMA and TE liquid. The addition
      of 10 microg g(-1) and 30 microg g(-1) 10B to water resulted in a decrease in the
      absolute thermal neutron fluence at 2 cm depth of about 2% and 8%, respectively,
      and a decreased penetration of thermal neutrons at depth for the 30 microg g(-1)
      10B concentration. For reference dosimetry of an epithermal neutron beam for
      BNCT, both water and TE liquid are suitable phantom materials. For practical
      reasons, water is therefore proposed as reference phantom material. For
      measurements requiring a solid phantom, PMMA is proposed. The lower gamma-ray
      dose in PMMA compared to water, however, needs to be taken into account.

PMID- 10958201
TI  - Tissue resistivity estimation in the presence of positional and geometrical
      uncertainties.
AB  - Geometrical uncertainties (organ boundary variation and electrode position
      uncertainties) are the biggest sources of error in estimating electrical
      resistivity of tissues from body surface measurements. In this study, in order to
      decrease estimation errors, the statistically constrained minimum mean squared
      error estimation algorithm (MiMSEE) is constrained with a priori knowledge of the
      geometrical uncertainties in addition to the constraints based on geometry,
      resistivity range, linearization and instrumentation errors. The MiMSEE
      calculates an optimum inverse matrix, which maps the surface measurements to the
      unknown resistivity distribution. The required data are obtained from four
      electrode impedance measurements, similar to injected-current electrical
      impedance tomography (EIT). In this study, the surface measurements are simulated
      by using a numerical thorax model. The data are perturbed with additive
      instrumentation noise. Simulated surface measurements are then used to estimate
      the tissue resistivities by using the proposed algorithm. The results are
      compared with the results of conventional least squares error estimator (LSEE).
      Depending on the region, the MiMSEE yields an estimation error between 0.42% and
      31.3% compared with 7.12% to 2010% for the LSEE. It is shown that the MiMSEE is
      quite robust even in the case of geometrical uncertainties.

PMID- 10958202
TI  - Locating steel needles in the human body using a SQUID magnetometer.
AB  - A technique has been developed, based on magnetic field measurements, to
      localize, in three dimensions, hypodermic and sewing needles lost in the human
      body. A theoretical model for the magnetic field generated by needles has been
      elaborated and experimentally validated. Using this model, the localization
      technique gives information about needle's centre, orientation and depth. The
      clinical measurements have been made using a SQUID system, with patients being
      moved under the sensor with the aid of an X-Y bed. The magnetic field associated
      with the remanent magnetization of the needle is acquired on-line and mapped over
      a plane. In all six cases that occurred, the technique allowed surgical
      localization of the needles with ease and high precision. This procedure can
      decrease the surgery time for extraction of foreign bodies by a large factor, and
      also reduce the generally high odds of failure.

PMID- 10958203
TI  - The accuracy of image registration for the brain and the nasopharynx using
      external anatomical landmarks.
AB  - We investigated the accuracy of 3D image registration using markers that are
      repeatedly applied to external anatomical landmarks on the head. The purpose of
      this study is to establish a lower limit of the errors that would occur in, for
      instance, MRI-SPECT matching, which in some situations can only be achieved using
      external landmarks. Marker matching was compared with (single-modality) volume
      matching for 20 MRI scans. The results were compared with a published expression
      for the target registration error (TRE) which gives the 3D distribution of the
      mismatch between both scans. It was found that the main error source is
      reapplying the external markers on the anatomical landmarks. The published
      expression describes the relative distribution of the TRE in space well, but
      tends to underestimate the actual registration error. This deviation is due to
      anisotropy in the error distribution of the marker position (errors in the
      direction perpendicular to the skin surface are in general much smaller than
      errors in other directions). A simulation of marker matching with anisotropy in
      the errors confirmed this finding. With four reapplied markers, the TRE is 6 mm
      or smaller in most regions of the head.

PMID- 10958204
TI  - Enhanced 3D PET OSEM reconstruction using inter-update Metz filtering.
AB  - We present an enhancement of the OSEM (ordered set expectation maximization)
      algorithm for 3D PET reconstruction, which we call the inter-update Metz filtered
      OSEM (IMF-OSEM). The IMF-OSEM algorithm incorporates filtering action into the
      image updating process in order to improve the quality of the reconstruction.
      With this technique, the multiplicative correction image--ordinarily used to
      update image estimates in plain OSEM--is applied to a Metz-filtered version of
      the image estimate at certain intervals. In addition, we present a software
      implementation that employs several high-speed features to accelerate
      reconstruction. These features include, firstly, forward and back projection
      functions which make full use of symmetry as well as a fast incremental
      computation technique. Secondly, the software has the capability of running in
      parallel mode on several processors. The parallelization approach employed yields
      a significant speed-up, which is nearly independent of the amount of data.
      Together, these features lead to reasonable reconstruction times even when using
      large image arrays and non-axially compressed projection data. The performance of
      IMF-OSEM was tested on phantom data acquired on the GE Advance scanner. Our
      results demonstrate that an appropriate choice of Metz filter parameters can
      improve the contrast-noise balance of certain regions of interest relative to
      both plain and post-filtered OSEM, and to the GE commercial reprojection
      algorithm software.

PMID- 10958205
TI  - Dosimetric verification of a commercial 3D treatment planning system for
      conformal radiotherapy with a dynamic multileaf collimator.
AB  - The dosimetric accuracy of a 3D treatment planning system (TPS) for conformal
      radiotherapy with a computer-assisted dynamic multileaf collimator (DMLC) was
      evaluated. The DMLC and the TPS have been developed for clinical applications
      where dynamic fields not greater than 10 x 10 cm2 and multiple non-coplanar arcs
      are required. Dosimetric verifications were performed by simulating conformal
      treatments of irregularly shaped targets using several arcs of irradiation with 6
      MV x-rays and a spherical-shaped, tissue-simulating phantom. The accuracy of the
      delivered dose at the isocentre was verified using an ionization chamber placed
      in the centre of the phantom. Isodose distributions in the axial and sagittal
      planes passing through the centre of the phantom were measured using double-layer
      radiochromic films. Measured dose at the isocentre as well as isodose
      distributions were compared to those calculated by the TPS. The maximum
      percentage difference between measured and prescribed dose was less than 2.5% for
      all the simulated treatment plans. The mean (+/-SD) displacement between measured
      and calculated isodoses was, in the axial planes, 1.0 +/- 0.6 mm, 1.2 +/- 0.7 mm
      and 1.5 +/- 1.1 mm for 80%, 50% and 20% isodose curves, respectively, whereas in
      the sagittal planes it was 2.0 +/- 1.2 mm and 2.2 +/- 2 mm for 80% and 50%
      isodose curves, respectively. The results indicate that the accuracy of the 3D
      treatment planning system used with the DMLC is reasonably acceptable in clinical
      applications which require treatments with several non-coplanar arcs and small
      dynamic fields.

PMID- 10958206
TI  - Trends of discordant fetal growth in monochorionic twin pregnancies.
AB  - We derived simple analytical relations representing trends of discordant fetal
      growth in monochorionic twins developing the twin-twin transfusion syndrome from
      an approximation of previously developed model equations. In severe twin-twin
      transfusion syndrome cases, the difference between the estimated fetal weights of
      both twins increases proportional to (t - 5)5 (t denotes gestational age in
      weeks) and the sum of both weights increases proportional to t3. Hence, the ratio
      between the difference of estimated fetal weights and the average of the two
      weights (difference average ratio) increases in proportion to (t - 5)5/t3. In
      mild cases, the difference between estimated fetal weights as well as the sum of
      the two weights increases proportional to t3. Therefore, the difference average
      ratio becomes a constant. Comparison with clinical data of severe and mild cases
      showed surprisingly good agreement except after laser coagulation of placental
      anastomoses. These relations may therefore enable us to distinguish between
      severe and mild developing twin-twin transfusion syndrome cases.

PMID- 10958207
TI  - Comments on 'Converting absorbed dose to medium to absorbed dose to water for
      Monte Carlo based photon beam dose calculations'.

PMID- 10958208
TI  - On the effective point of measurement of cylindrical ionization chambers for
      proton beams and other heavy charged particle beams.

PMID- 10958209
TI  - Overview: smoke gets in your gut.

PMID- 10958210
TI  - Smoking and gastro-oesophageal reflux disease.
AB  - The role of smoking in the pathogenesis of gastrooesophageal reflux disease has
      been controversial since the early 1970s when Stanciu reported the two to be 92%
      epidemiologically associated (a study subsequently challenged by inconsistencies
      in the observational data). Mechanistically, reflux disease is caused by
      excessive oesophageal acid exposure, which is potentially attributable to
      excessive reflux events and/or prolonged acid clearance. Currently, the best
      available pH monitoring data confirm that smoking increases oesophageal acid
      exposure. Smoking reduces lower oesophageal sphincter (LOS) pressure and
      predisposes to strain-induced reflux. Consistent with this, smoking has been
      shown to cause an increased number of reflux events that are not attributable to
      increased transient LOS relaxations, but rather are associated with deep
      inspiration and coughing. Once reflux occurs, acid is cleared from the oesophagus
      by a two-step process consisting of oesophageal peristalsis followed by
      neutralization of the residual acid by swallowed saliva. Smoking prolongs acid
      clearance by decreasing salivation. The effects of smoking on LOS tone and acid
      clearance are most likely mainly due to nicotine but are incompletely understood.
      Transdermal nicotine has similar effects to smoking on LOS pressure and
      salivation. Thus, although perhaps not a dominant risk factor, smoking and
      nicotine impact on pathophysiological variables of gastro-oesophageal reflux
      disease. In itself, smoking cessation is unlikely to cure severe
      gastrooesophageal reflux disease, but, along with appropriate pharmacological
      therapy, it may be beneficial.

PMID- 10958211
TI  - Smoking and peptic ulcer in the Helicobacter pylori era.
AB  - Before the recent understanding of the central importance of Helicobacter pylori
      in the pathogenesis of peptic ulcer disease, smoking had been regarded as an
      important contributor to the cause and perpetuation of the disease. In this
      review, we find that (1) clinical observations indicate that smokers are more
      likely to develop ulcers, ulcers in smokers are more difficult to heal, and
      relapse of ulcer disease is more likely in smokers, (2) smoking adversely affects
      the gastroduodenal mucosal protective mechanisms, thus predisposing to ulcer
      disease, (3) smoking adversely affects gastroduodenal motility, allowing reflux
      of harmful duodenal contents into the stomach, (4) smokers appear to be at higher
      risk of becoming infected with H. pylori and this increased risk may be due to
      the adverse effects of smoking on antioxidants or the immune system that may
      interfere with the normal protection against H. pylori, and (5) once H. pylori is
      eradicated in smokers, they appear to be at no greater risk of peptic ulcer
      disease. We conclude that smoking in itself appears not to be an independent
      ulcerogen, but may act by augmenting the harmful effects of H. pylori, both by
      adversely affecting upper gastrointestinal mucosal protection and physiology and
      by increasing the risk of H. pylori infection. Thus, we recommend that
      appropriate advice to ulcer patients who smoke continues to be: stop smoking.

PMID- 10958212
TI  - Smoking and inflammatory bowel disease.
AB  - It is well established that smoking cigarettes is associated with Crohn's disease
      (CD) and that non-smoking is associated with ulcerative colitis (UC).
      Furthermore, there is convincing evidence that smoking cigarettes has a negative
      effect on the course of CD, and that smoking cigarettes may improve the disease
      severity or have a 'protective' effect in some patients with UC. Despite these
      well-described associations, the mechanism by which cigarette smoking affects CD
      and UC is not known. Researchers have studied the systemic effects, cellular and
      humoral immune effects, mucosal changes, and the intestinal permeability changes
      with inflammatory bowel disease (IBD) and smoking. To date, none of these studies
      adequately explains the observed clinical patterns. It has been assumed that
      nicotine is the active agent in these associations, but clinical trials of
      nicotine chewing gum and transdermal nicotine in UC have shown limited benefit,
      and have been complicated by significant side-effects. Topical delivery systems
      for nicotine therapy are currently under development and await future clinical
      trials.

PMID- 10958213
TI  - Smoking and hepato-biliary disease.
AB  - The effect of cigarette smoking has been assessed in several hepato-biliary
      diseases, although in only a few was smoking the main focus of the study. Other
      than in primary sclerosing cholangitis, the relationships found are not strong
      and it remains unclear whether any are causal in nature - particularly in the
      absence of clearly demonstrated biological mechanisms. Nevertheless, many studies
      have found a modest but definite association between smoking and gallstone
      disease. As smoking is so prevalent in many countries, the public health impact
      of even a weak causal relationship would be considerable.

PMID- 10958214
TI  - Smoking and pancreatic disorders.
AB  - Cigarette smoking is a major risk factor for pancreatic cancer and probably
      pancreatitis. It has been reported that patients with chronic pancreatitis are 16
      times more likely to develop pancreatic cancer than normal individuals. Nicotine,
      a major component of tobacco and an addicted drug of abuse in humans, appears to
      play a role in the aetiology of both pancreatic cancer and pancreatitis. This
      review discusses major published reports pertaining to the influence of nicotine
      on these diseases in humans and the probable effects of nicotine on the
      pathophysiology of the pancreas in animal models. A hypothetical pancreatic
      acinar cell model showing multiple signal transduction pathways is presented
      relating to possible mechanisms of action of nicotine on the pathophysiology of
      the pancreas.

PMID- 10958215
TI  - Long-term management of gastro-oesophageal reflux disease with omeprazole or open
      antireflux surgery: results of a prospective, randomized clinical trial. The
      Nordic GORD Study Group.
AB  - BACKGROUND AND AIM: The efficacy of antireflux surgery (ARS) and omeprazole
      treatment in the control of gastrooesophageal reflux disease (GORD) are well
      established. We have compared these two therapeutic options in a randomized,
      clinical trial. PATIENTS AND METHODS: Three hundred and ten patients with erosive
      oesophagitis were enrolled into the trial. After a run-in period when all
      patients had < or = 40 mg of omeprazole daily to heal the oesophagitis and
      relieve symptoms, 155 patients were randomized to continuous omeprazole therapy
      and 155 to open antireflux surgery, of whom 144 later had an operation. One
      hundred and thirty-nine and 129 in the omeprazole and antireflux surgery groups,
      respectively, completed the 3-year follow-up. Symptoms, 24-h pH monitoring and
      endoscopy were used to document the outcome. Quality of life was evaluated by the
      psychological general well-being (PGWB) index and the gastrointestinal symptom
      rating scale (GSRS). RESULTS: Analysis of time to treatment failure (defined as
      moderate to severe GORD symptoms for > or = 3 days during the last 7 days,
      oesophagitis or changed therapy) revealed a significant difference in favour of
      antireflux surgery (P = 0.0016). Seventeen patients originally submitted to
      antireflux surgery experienced symptom relapse alone, 14 had oesophagitis at
      endoscopy and another six had omeprazole for different reasons, leaving 97
      patients in clinical remission after 3 years. The corresponding figures in the
      omeprazole arm were 50 relapses, 18 with oesophagitis, two had surgery, leaving
      77 patients in remission. Allowing a dose adjustment in the case of relapse in
      those on omeprazole therapy to either 40 or 60 mg, the curves describing the
      failure rates were not significantly different from each other. Quality of life
      assessment showed a comparable outcome in the two study groups. CONCLUSION: In
      this randomized multicentre trial we found antireflux surgery to be very
      efficacious in controlling GORD, a level of control which could also be achieved
      by omeprazole provided that advantage was taken of the opportunity of adjusting
      the dose.

PMID- 10958217
TI  - Early changes of ileoanal pouch mucosa in patients with ulcerative colitis.
AB  - BACKGROUND/AIMS: Following closure of the protective ileostomy the mucosa of
      ileoanal pouches undergoes characteristic changes, which are thought to be caused
      by the new luminal environment Conventional histopathology and
      immunohistochemical markers were compared in serial pouch biopsies from patients
      with ulcerative colitis (UC) in the early period of function. METHODS: Biopsy
      specimens were obtained from nine patients during ileostomy closure, 24 h after
      the first bowel action, then 6 days, 6 weeks and 3 months postoperatively.
      Cryostat sections were stained with haematoxylin and eosin (H&E) for assessment
      of mucosal inflammation and morphometry, and for lymphocyte subtypes (CD3, CD4,
      CD8), macrophages (CD68), common leucocyte antigen (CD45), and HLA-DR, using a
      three-stage immunoperoxidase reaction. RESULTS: Within 5 days of pouch function
      the index for mucosal atrophy (villous height/total mucosal thickness ratio)
      decreased significantly from a median (range) of 0.66 (0.39-0.69) to 0.52 (0.37
      0.61)(P = 0.02). Intraepithelial lymphocyte counts diminished from 10.1 (5.6
      21.1) to 7.0 (2.2-8.2)(P = 0.007) per 100 epithelial cells and remained so. In
      the lamina propria, apart from a transient increase in CD3 positive cells at 5
      days (from 92.7 (58-165) to 100.5 (57-234) per unit area; P = 0.038), no
      significant changes were observed. H&E grading and HLA-DR expression remained
      unchanged. CONCLUSIONS: While there was no significant change in mucosal
      morphology and mucosal leucocyte subpopulations after 24 h of pouch function, the
      ileal pouch mucosa in UC patients had responded significantly within 5 days.
      Further studies into cell function and signalling are required.

PMID- 10958218
TI  - Crohn's disease incidence in Cardiff from 1930: an update for 1991-1995.
AB  - OBJECTIVE: To report the incidence of Crohn's disease in the city of Cardiff
      between 1991 and 1995, in relation to the data of the preceding 65 years.
      METHODS: The incidence of Crohn's disease was studied by collecting information
      from clinical records, the department of pathology database and a questionnaire
      sent to local family practitioners. RESULTS: Eighty-four new patients with
      Crohn's disease, and resident in Cardiff, were diagnosed between 1991 and 1995.
      The mean incidence for this quinquennium was 56 cases per 10(6) population per
      year (95% confidence interval, 44-68). There was a female predominance,
      particularly in young adults, with an overall male to female ratio of 0.47.
      Colorectal disease was the most common site of disease at the time of diagnosis.
      CONCLUSIONS: In relation to the findings of our previous studies, the data
      suggest that the overall incidence of Crohn's disease is now stable, but that the
      proportion with colorectal disease continues to increase and there is a marked
      female preponderance in Crohn's disease presenting in young people.

PMID- 10958216
TI  - Rabeprazole for the prevention of recurrent erosive or ulcerative gastro
      oesophageal reflux disease. Rabeprazole Study Group.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of rabeprazole 10 mg and 20
      mg versus placebo for the prevention of endoscopically demonstrable relapse in
      patients previously diagnosed with erosive or ulcerative gastro-oesophageal
      reflux disease (GORD) who had no oesophageal erosions or ulcerations at study
      entry. The study also assessed the effectiveness of rabeprazole in preventing
      GORD symptom recurrence and reductions in quality of life. DESIGN/METHODS: The
      trial used a multicentre, randomized, double-blind, parallel-group design and
      enrolled 288 male and female outpatients of > or =18 years of age. Patients were
      assigned to treatment with either rabeprazole 10 mg or 20 mg once daily in the
      morning (QAM) or placebo and followed for 52 weeks. RESULTS: Both rabeprazole
      doses were significantly more effective than placebo in preventing endoscopically
      demonstrable GORD relapse (P<0.001 versus placebo). The cumulative relapse rate
      for rabeprazole 10 mg at week 52 was 23%; for rabeprazole 20 mg, 14%; and for
      placebo, 71%. Both rabeprazole doses were also significantly superior to placebo
      in preventing relapse of heartburn frequency (P<0.001 for all comparisons between
      rabeprazole and placebo), with no significant differences between the two doses.
      Rabeprazole was also significantly more effective than placebo in preventing
      relapse of day-and night-time heartburn severity, maintaining overall patient
      well-being, and reducing antacid use. Both rabeprazole doses were well tolerated;
      most treatment-emergent adverse events were mild or moderate. There were no
      clinically significant changes in clinical laboratory values, thyroid function
      tests, vital signs, or electrocardiograms. CONCLUSION: Once-daily treatment with
      rabeprazole 10 mg or 20 mg is effective and well tolerated in preventing relapse
      of erosive or ulcerative GORD and associated symptoms and maintaining quality of
      life.

PMID- 10958219
TI  - Significance of nuclear morphometry as a diagnostic tool in fine-needle aspirates
      of the liver.
AB  - OBJECTIVE: Classification of hepatic tumours and tumour-like conditions can
      sometimes be difficult to establish by light microscopy. Our aim was to determine
      the value of computerized interactive nuclear morphometry in the preoperative
      prediction of primary or metastatic malignancy as opposed to non-malignant
      lesions, in fine-needle aspirates (FNA) of hepatic lesions. METHODS: Alcohol
      fixed, Papanicolaou-stained FNA smears of 99 histologically proven hepatocellular
      carcinomas (HCCs), metastatic neoplasms and benign lesions were measured by
      computerized image analysis with regard to nuclear major axis, minor axis,
      perimeter, area, shape factor and hyperchromasia. Data were coded, entered into a
      computerized database, and statistically analysed with SPSS programs. RESULTS:
      Tukey HSD test for multiple comparisons, assessed for all features except
      hyperchromasia, showed that the mean values of morphometric features of
      nonmalignant cells were significantly different from those of malignant cells,
      either primary or metastatic, whereas differences between morphometric
      characteristics of HCCs and metastatic neoplasms were insignificant. Kruskal
      Wallis analysis of variance revealed that hyperchromasia varied among the three
      groups of samples proportionally to the other nuclear features. The mean
      differences of all evaluated nuclear variables except minor axis were significant
      between grades II & III and grade IV HCCs. Morphometric mean values of well
      differentiated HCCs differed significantly in comparison with those of non
      malignant lesions; however, some degree of overlap was observed in the ranges of
      minor axis and hyperchromasia mean values. CONCLUSIONS: The three most important
      cytological criteria of nuclear malignancy (hyperchromasia, enlargement and
      anisonucleosis), when quantified by morphometry, may be helpful in the
      differential diagnosis between non-cancerous liver lesions and HCCs (even those
      of high differentiation), since all the morphometric data showed pronounced
      differences between malignant and benign groups. Morphometry may also be used as
      a complementary tool in the cytological grading of HCCs.

PMID- 10958220
TI  - An improved ex vivo method of primary porcine hepatocyte isolation for use in
      bioartificial liver systems.
AB  - INTRODUCTION: Primary porcine hepatocytes are commonly, used in bioartificial
      liver devices and for in vitro studies of hepatocyte function. Although in vivo
      isolation of porcine hepatocytes can give high yield and viability, such methods
      are time-consuming and expensive, requiring specialist surgical facilities. AIM:
      To develop a simple, low-cost, high viability, high yield, reproducible ex vivo
      method for obtaining functional porcine hepatocytes for use in bioartificial
      liver systems. METHODS: Weanling piglets (12 kg) were killed with pentobarbitone
      sodium, the infra-hepatic inferior vena cava was clamped and the supra-hepatic
      inferior vena cava cannulated. The whole liver was retrogradely perfused in situ
      with cold saline and excised, followed by an ex vivo open-loop and re-circulating
      perfusion method (at 37 degrees C) in five steps. The liver was disrupted,
      sequentially filtered in washing buffer, purified by centrifugation and
      resuspended in Williams E medium. Viability and cell number were assessed using
      trypan blue exclusion. The cells were subsequently cultured in serum-free
      chemically-defined medium and function was assessed. RESULTS: The time interval
      from when the animals were killed to the final cell wash was 105+/-5 min (n =
      20). Cell viability was 85+/-6% with a yield of (2.4+/-0.5) x 10(10) from 12+/-1
      kg piglets using 0.03% (w/v) collagenase (n = 20). Hepatocytes from all
      isolations were successfully plated and grown in monolayer culture. In freshly
      isolated hepatocytes (day 0) total protein content (TP) was 1.2+/-0.1 mg/10(6)
      cells (n = 5) and 1.2+/-0.3 mg/10(6) cells (n = 5) for day 2 monolayer cultures,
      corresponding to approximately 9x10(6) hepatocytes per dish. The percentage of
      total LDH released into the medium was 13+/-4% for day 0 and 8+/-4% at day 2;
      conversely, intracellular LDH activities were 87+/-4% and 92+/-4% of the total,
      respectively. The urea synthesis rate was 196+/-36 nmol/h/mg total protein at day
      0 (n = 5) and 292+/-62 nmol/h/mg protein (n = 9) at day 2. The total P450 content
      was 99+/-11 pmol/mg total protein for fresh cells (n = 5) and maintained at 89+/
      35 pmol/mg total protein in day 2 cultures. CONCLUSIONS: This ex vivo method
      provides a high viability, high yield, cost-effective and rapid technique for
      isolating functional porcine hepatocytes with high plating efficiency, which
      compares favourably with results obtained using complex in vivo techniques.

PMID- 10958221
TI  - Incidence of vertebral fractures in the first three months after orthotopic liver
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: High rates of bone loss and increased fracture
      incidence have been reported in patients undergoing liver transplantation, mainly
      within the first post-operative year. The pathogenesis of post-transplantation
      bone disease has not been clearly established, but the high doses of
      glucocorticoids used for immunosuppression may contribute. The use of lower doses
      in recent years has been associated, in some studies, with lower rates of bone
      loss and decreased fracture incidence. The aim of this prospective study was to
      establish the incidence of vertebral fractures in the first 3 months in patients
      undergoing liver transplantation for chronic liver disease and to identify risk
      factors for fracture in these patients. DESIGN AND METHODS: Thirty-seven adults
      with end-stage liver disease were studied prospectively prior to and 3 months
      after liver transplantation. Vertebral fractures were assessed semi
      quantitatively from lateral spine X-rays and bone mineral density measured using
      dual energy X-ray absorptiometry. RESULTS: Prior to transplantation, prevalent
      vertebral fractures were present in 13 patients (35%). New fractures developed
      after transplantation in 10 patients (27% of total) and were significantly more
      common in those with a prevalent vertebral fracture pre-operatively (P<0.02).
      Osteoporosis, defined as a bone mineral density T score below -2.5, was present
      in 39% of patients prior to transplantation, but bone mineral density was not
      helpful in predicting incident fracture, whether measured before or after
      transplantation. Over the 3-month study period, significant bone loss occurred in
      the femoral neck (P<0.05) but not the lumbar spine. CONCLUSIONS: Our results
      demonstrate a high incidence of vertebral fracture in the first 3 months after
      liver transplantation and indicate that prevalent vertebral fracture is an
      important risk factor for the subsequent development of fracture in these
      patients. Prevention of post-transplantation bone disease should focus both on
      optimizing bone mass prior to transplantation and preventing bone loss in the
      early post-operative period.

PMID- 10958222
TI  - Increase of serum beta2-microglobulin in patients affected by HCV correlated
      hepatocellular carcinoma.
AB  - OBJECTIVE: HLA antigens influence tumour growth and spreading, but the mechanism
      is still unclear. Increased serum levels of beta2-microglobulin (beta2MG) have
      been found in several chronic inflammatory and tumour diseases. The aim of the
      present study was to analyse the relationship between serum beta2MG levels and
      some markers of tumour progression, to verify the reliability of this parameter
      as a marker of hepatocellular carcinoma (HCC) progression. DESIGN: We studied 50
      patients with hepatitis C virus (HCV) correlated HCC, 50 patients affected by
      chronic hepatitis C and 20 healthy controls. We performed a statistical analysis
      on the data obtained from haematological withdrawals in patients and healthy
      subjects. METHODS: Serum beta2MG levels were determined by an immunoturbidimetric
      method (normal values range from 0.8 to 27 microg/ml). Diagnosis of HCC was
      performed on the basis of haematochemical parameters (alpha-fetoprotein) and
      instrumental examinations (ultrasonography and computed tomography). In order to
      perform the statistical analysis we used the Wilcoxon non-parametric rank test
      and the Spearman log-rank correlation test RESULTS: Patients with HCC showed
      higher serum beta2MG levels than did chronic hepatitis C patients (36+/-16.5
      microg/ ml versus 2.3+/-0.8 microg/ml; P<0.0001) or healthy subjects (36+/-16.5
      microg/ml versus 1.6+/-0.4 microg/ml; P<0.0001). We found a positive correlation
      between beta2MG and interleukin-6 (IL-6) (r = +0.3; P = 0.05), beta2MG and alpha
      fetoprotein (r = +0.4; P = 0.005), beta2MG and tumour size (r = +0.3; P = 0.02).
      CONCLUSIONS: An increase in the beta2MG serum level reflects the tumour size and
      seems to be a consequence of the stimulation on hepatocytes by humoral components
      of immunological response, such as IL-6. Weakening of the immune system, due to
      IL-6, may be responsible for a more severe progression of HCC and the
      hyperexpression of beta2MG.

PMID- 10958223
TI  - Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at
      presentation.
AB  - BACKGROUND AND AIMS: The aetiology of chronic liver disease leading to
      hepatocellular carcinoma (HCC) and the clinical characteristics at the time of
      presentation vary considerably among different parts of the world and over time.
      The number of patients seen at our institution has increased as compared to a
      period 20 years earlier. We investigated baseline characteristics of patients
      with hepatocellular carcinoma such as cirrhosis, hepatitis virus markers, age at
      presentation and stage of the tumour in an area with low prevalence of viral
      hepatitis. METHODS: All 245 patients seen at the Department of Gastroenterology
      and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998
      were included in this retrospective study, and 19 different clinical
      characteristics were studied. RESULTS: The median age at detection of HCC was
      63.3 years, and alcoholic liver disease (35.1%) and hepatitis C virus (HCV)
      infection (36.7%) were the most frequent underlying diseases. Both chronic
      alcoholism and HCV infection as risk factors were present in 6.9% of the
      patients. Liver cirrhosis was present in 86.5%. At the time of diagnosis, 43.5%
      had multi-nodular tumours. Of the remaining patients with a single nodule, only
      10% had HCC < or =2 cm. Most of our patients presented at a late stage of the
      disease (TNM stage 3 29.4%, TNM stage 4 69.7%; Okuda stage 2 65.7%, Okuda stage 3
      18.0%). Due to the late stage of the disease at the time of presentation, 145
      patients (59.2%) received palliative care only, 24 (9.8%) underwent liver
      resection, 38 (15.5%) liver transplantation and 38 (15.5%) chemotherapy.
      CONCLUSIONS: In this large single-centre series of HCC, the dominant contribution
      of HCV infection and chronic alcohol abuse as the underlying aetiology is
      documented. Diagnosis is usually made very late as reflected in the high
      proportion of patients in TNM stages 3 and 4 or Okuda stages 2 and 3. This
      resulted in a high percentage of patients who received palliative care only and
      very few who were eligible for treatment modalities with curative potential such
      as resection and liver transplantation.

PMID- 10958224
TI  - Validation of phone interview for follow-up in clinical trials on dyspepsia:
      evaluation of the Glasgow Dyspepsia Severity Score and a Likert-scale symptoms
      test.
AB  - OBJECTIVE: To validate two widely used dyspepsia scores performed by phone
      interview. DESIGN: Spanish translations of the Glasgow Dyspepsia Severity Score
      and a Likert-scale symptomatic test were evaluated. Responsiveness to the
      treatment, validity of the tests, and reproducibility of tests performed by phone
      interview were assessed. SETTING: Gastroenterology and endoscopy unit of a county
      hospital. PARTICIPANTS: Group I consisted of 16 ulcer patients undergoing
      Helicobacter pylori eradication; Group II consisted of 29 healthy volunteers; and
      Group III consisted of 95 patients undergoing upper endoscopy. MEASUREMENTS:
      Glasgow Severity Dyspepsia Score and Likert test. RESULTS: Both tests showed
      adequate improvement (responsiveness) after H. pylori eradication. With regard to
      validity, the Glasgow and Likert test were significantly higher in 95 patients
      undergoing endoscopy than in 29 healthy controls. Analysis of reproducibility
      showed that intraobserver variation was low on both the Glasgow and Likert
      scores. No differences were found between consecutive tests regardless of whether
      both were performed by phone (24 patients) or one by phone and the other by
      clinical interview (40 patients). Interobserver variation analysis showed that
      the Glasgow test remained highly reproducible even when performed by different
      observers using different methods (clinical interview 8.83, phone 8.44, P =
      0.12). By contrast, Likert-scale tests showed significant differences between
      observers for all symptoms except abdominal pain. CONCLUSIONS: (1) The Glasgow
      score is highly reproducible even when performed by different observers and using
      different methods. (2) By contrast, Likert tests show greater variability. To be
      reproducible in different conditions, they need to be performed by the same
      observer.

PMID- 10958225
TI  - Fatal hepatotoxicity after re-exposure to isoflurane: a case report and review of
      the literature.
AB  - A 76-year-old Caucasian woman developed fulminant hepatic necrosis 6 days after
      an uneventful operation under isoflurane anaesthesia. Laboratory findings
      included elevated bilirubin, grossly elevated transaminases and prolonged
      prothrombin time. Radiological investigation showed no evidence of extra-hepatic
      disease. Serological studies were negative for acute viral hepatitis and
      autoimmune disease. The patient may have been previously sensitized by exposure
      to isoflurane 3 years previously but antibodies to tri-fluoro acetate, present in
      70% of cases of halothane hepatitis, were not detected in pre-operative or
      postoperative samples of blood. On the seventh postoperative day the patient died
      and postmortem examination demonstrated centrilobular necrosis of the liver, with
      a histological pattern similar to changes associated with halothane hepatitis.

PMID- 10958226
TI  - Gastric perforation of a left lobe amoebic liver abscess.
AB  - Liver abscess is the most common extra-intestinal manifestation of invasive
      amoebiasis. Perforation of the abscess is a potential life-threatening
      complication. We report a case where perforation into the stomach was
      successfully managed conservatively. The initial diagnosis in this case was made
      by gastroscopy and biopsy. To our knowledge, only five cases of gastric
      perforation of an amoebic liver abscess have been reported in the English
      literature. In none of these cases was the diagnosis established by histology of
      gastric biopsy specimens.

PMID- 10958227
TI  - Bibliography. Current world literature. Interstitial lung disease.

PMID- 10958228
TI  - Interferons and interstitial lung disease.

PMID- 10958229
TI  - Small airway involvement in interstitial lung disease: radiologic evidence.
AB  - High resolution computed tomography (HRCT) has considerably improved the ability
      to diagnose and characterize interstitial lung disease (ILD). This paper assesses
      the role of HRCT in evaluating small airway disease associated with ILD
      particularly sarcoidosis, hypersensitivity pneumonitis, and interstitial
      pulmonary fibrosis.

PMID- 10958230
TI  - The role of pulmonary function testing in pulmonary fibrosis.
AB  - Interstitial lung diseases are characterized by disruption of the distal
      pulmonary parenchyma. The clinical history manifestations, cough and dyspnea, and
      physical exam manifestations, inspiratory crackles, are nonspecific. Pulmonary
      function testing aids in the evaluation and management of patients with
      interstitial lung disease although the pattern of abnormality is nonspecific.
      Pulmonary function testing can provide an estimate of histologic severity but not
      a definitive quantification of histologic fibrosis or inflammation. Pulmonary
      function tests can provide a baseline estimation of prognosis and be used to
      monitor disease progression or response to therapy. The forced vital capacity and
      diffusion capacity are the most valuable serial measurements, but further data
      are required to examine composite scoring and exercise gas exchange.

PMID- 10958231
TI  - Induced sputum: diagnostic value in interstitial lung disease.
AB  - Induced sputum by inhalation of hypertonic saline solution is a noninvasive
      technique used to collect cellular and soluble material from lung airways. During
      the past decade, this method has been widely used to assess airway inflammation
      in asthma and chronic obstructive pulmonary disease, since it produces reliable
      results and compares favorably to other invasive techniques, such as biopsy and
      bronchoalveolar lavage (BAL). Induced sputum has been recently used to study
      interstitial lung disease (ILD), more specifically pneumoconiosis, sarcoidosis,
      and nongranulomatous ILD. Moreover, results from induced sputum supplied
      information comparable to BAL findings for occupational lung disease and were
      able to distinguish sarcoidosis patients from healthy subjects and from patients
      with nongranulomatous ILD. Although induced sputum had previously provided
      promising results in assessing patients with ILD, its diagnostic role has not yet
      been well defined. Further studies of the evaluation by induced sputum of grading
      of severity, follow-up of disease, and effects of treatment are needed.
      Additionally, to date no specific studies have been undertaken to evaluate the
      safety and functional effects of sputum induction on patients with ILD. In
      conclusion, we think that induced sputum can be used as a complementary tool to
      BAL both in research and in clinical monitoring of patients with ILD.

PMID- 10958232
TI  - Smoking-related interstitial lung diseases.
AB  - Interstitial lung diseases (ILDs) encompass diverse clinicopathological disease
      entities ranging from idiopathic interstitial pneumonia (IIP) to interstitial
      pneumonia accompanied by collagen vascular diseases and diseases related to
      smoking, drug reactions, occupational environments, infections, and malignancies.
      Our focus is on the smoking-related interstitial lung diseases. Specifically, we
      focus on reports suggesting that chronic smoking is deeply involved in the
      disease pathogenesis and on reports suggesting that chronic smoking may influence
      the clinical course in terms of either disease severity or progression. Pulmonary
      Langerhans' cell granulomatosis (PLCG), desquamative interstitial pneumonia
      (DIP), respiratory bronchiolitis with interstitial lung diseases (RB-ILD),
      interstitial pneumonia associated with rheumatoid arthritis, acute respiratory
      distress syndrome (ARDS), and idiopathic pulmonary fibrosis (IPF) are covered.

PMID- 10958233
TI  - The role of viruses in the pathogenesis of hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is a worldwide lung disease caused by an immune
      response to a variety of mostly organic inhaled antigens. Only a small percentage
      (for example, 3 in 1000 dairy farmers) of subjects exposed to HP antigens develop
      the disease. It is possible that cofactors are needed to render the patient
      hypersensitive to environmental antigens; recent studies suggest that a viral
      infection could be such a trigger factor. Mice infected once with Sendai virus
      and simultaneously sensitized with HP antigens develop an enhanced response to
      the antigen that persists long after the transient viral infection has waned.
      Moreover, viral antigens were found in the lavage cells and lung tissue of
      patients with HP. Viral infections are known modulators of the immune response;
      viruses increase the antigen-presenting capacity of alveolar macrophages,
      decrease phagocytosis and antigen clearance, induce the release of pro
      inflammatory cytokines, and favor the proliferation of Th1 T-lymphocytes (cells
      putatively associated with HP).

PMID- 10958234
TI  - Interstitial lung disease in systemic lupus erythematosus.
AB  - Systemic lupus erythematosis (SLE) is a heterogenous disease of unknown etiology.
      It is not uncommon to see pleuropulmonary involvement in isolation or along with
      the involvement of other organ systems in SLE. Pulmonary manifestations of SLE
      can involve the pleura, lung parenchyma, airways, pulmonary vasculature, and the
      respiratory muscles. In this review we discuss two important pulmonary
      manifestations of SLE: acute lupus pneumonitis and diffuse interstitial lung
      disease. These two conditions have a major impact on the mortality and morbidity
      of patients with SLE and it is essential to recognize and treat them
      appropriately. High-resolution computed tomographic scans of the chest and
      pulmonary function tests help to establish a diagnosis and aid long-term follow
      up of these patients. High-dose corticosteroids are the mainstay of treatment for
      the two conditions, although other agents such as cyclophosphamide, azathioprine,
      intravenous gamma globulin, and plasmapheresis have been used with varying
      degrees of success.

PMID- 10958235
TI  - Pulmonary capillaritis.
AB  - Vasculitis, inflammation, and necrosis of blood vessels can involve any size or
      type of vessel in the pulmonary vasculature, including the capillaries, so-called
      capillaritis. Although pulmonary capillaritis is a histopathologic diagnosis that
      is not pathognomonic of a specific disorder, it usually signals the presence of
      an underlying systemic vasculitis or collagen vascular disease. Patients with
      pulmonary capillaritis usually present with bilateral infiltrates on chest
      radiographs and can be acutely ill with diffuse alveolar hemorrhage that may be
      life threatening. Therapy depends on diagnosis of the underlying disease that
      gave rise to the capillaritis. Since many of the disorders leading to
      capillaritis are treated by immunosuppression with corticosteroids and
      cyclophosphamide or azathioprine, infection must be excluded early in the course
      of therapy.

PMID- 10958236
TI  - Pulmonary leptospirosis.
AB  - Leptospirosis is a worldwide zoonosis affecting wild and domestic mammals. It is
      most commonly transmitted to humans by indirect contact with infected animals.
      Vascular injury, mainly capillary damage, and hemorrhagic diathesis are prominent
      features in the affected organs. The most severe form of the disease presents
      with high fever, intense jaundice, hemorrhagic diathesis, hepatic and renal
      dysfunction, mental status changes, and cardiovascular collapse. Focal or diffuse
      areas containing alveoli filled with erythrocytes characterize the pulmonary
      involvement. These latter conditions, although unusual, are associated with
      significant mortality.

PMID- 10958237
TI  - Hypercalcemia in granulomatous disorders: a clinical review.
AB  - Hypercalcemia occurs in most granulomatous disorders. High serum calcium levels
      are seen in about 10% of patients with sarcoidosis; hypercalciuria is about three
      times more frequent. Tuberculosis, fungal granulomas, berylliosis, and lymphomas
      are other conditions that are associated with disorders of calcium metabolism.
      These abnormalities of calcium metabolism are due to dysregulated production of
      1,25-(OH2)D3 (calcitriol) by activated macrophages trapped in pulmonary alveoli
      and granulomatous inflammation. Undetected hypercalcemia and hypercalciuria can
      cause nephrocalcinosis, renal stones, and renal failure. Corticosteroids cause
      prompt reversal of the metabolic defect. Chloroquine, hydroxychloroquine, and
      ketoconazole are the drugs that should be used if the patient fails to respond or
      develops dangerous side effects to corticosteroid therapy.

PMID- 10958238
TI  - Sarcoidosis in developing countries.
AB  - Sarcoidosis is seen in different parts of India and other developing countries
      with almost similar frequency as in the West. It was largely due to lack of
      awareness and non-availability of investigations for diagnosis that the disease
      was reported to be rare in the past. A combination of clinical, radiologic, and
      histologic criteria are used to diagnose sarcoidosis. A confident exclusion of
      other causes of granuloma formation, especially tuberculosis, is required.
      Absence of mycobacteria and of caseation in the histologic specimens and presence
      of skin anergy to tuberculin help make a diagnosis. Transbronchial lung biopsy
      obtained with the help of fiberoptic bronchoscopy is positive in about 80% of
      patients. Corticosteroids are used to treat patients with symptoms and those
      showing active organ involvement. Aggressive treatment is required for patients
      with acute and severe pulmonary, cardiac, ocular, or neurologic involvements.

PMID- 10958239
TI  - Pleural involvement in sarcoidosis.
AB  - Pleural sarcoidosis is no longer considered rare, as it occurs in about 3% of all
      cases of sarcoidosis. However, newer methods of detection may boost this level
      higher. High-resolution computed tomographic scanning has increased our detection
      of pleural nodules and pleural thickening. Other manifestations include
      pneumothorax, chylothorax, and hemothorax. Further studies of large numbers of
      patients are needed to determine the true prevalence of pleural involvement in
      sarcoidosis.

PMID- 10958240
TI  - Guidelines and recommendations for antimicrobial minimum inhibitory concentration
      (MIC) testing against veterinary mycoplasma species. International Research
      Programme on Comparative Mycoplasmology.
AB  - The absence of standardised procedures for minimum inhibitory concentration (MIC)
      testing of antimicrobial agents against veterinary mycoplasma and ureaplasma
      species (Mollicutes) has made it difficult to compare results originating from
      different laboratories. This report, prepared on behalf of the International
      Research Programme on Comparative Mycoplasmology (IRPCM), offers guidelines and
      recommendations for veterinary MIC testing of these organisms in an effort to
      rectify this problem. The subjects discussed include suitable media for broth and
      agar MIC assays, storage and preparation of antimicrobial agents, standardisation
      of mycoplasma inocula for MIC tests, validation of equipment, incubation
      conditions, and determination of MIC end points. A standard medium for all
      veterinary mycoplasma MIC tests cannot currently be recommended, owing to the
      diversity of nutritional requirements of different mycoplasma species. Instead
      mycoplasma broths or agars giving optimal growth of specific mycoplasmas or
      ureaplasmas are recommended, as suboptimal growth may lead to falsely low MIC
      results. The importance of using standardised mycoplasma inocula, for assays
      using either solid or liquid media is stressed. The growth phase may be less
      important as lag phase and logarithmic phase cultures of Mycoplasma
      gallisepticum, M. synoviae, M. bovis and M. hyopneumoniae have given very similar
      results in liquid MIC assays. The liquid method of Tanner and Wu and the agar
      method described by Hannan et al. are compared and described in detail. Methods
      for calculating MIC50s and MIC90s are described and the interpretation of results
      discussed. Methods for assessing mycoplasmacidal (MMC) activity of antimicrobial
      agents are also described. Adoption of these guidelines should lead to more
      consistent MIC results being obtained between laboratories.

PMID- 10958241
TI  - Hyperketonemia and the impairment of udder defense: a review.
AB  - The objective of this study was to review the possible relationships between
      hyperketonemia and the function of phagocytes with respect to the bovine udder
      defense mechanism. We hypothesize that an increased incidence of clinical
      mastitis in high-producing cows is caused by the impairment of the udder defense
      mechanism during hyperketonemia. First, we review the acute phase of udder
      defense mechanisms after intramammary infection. The physiological changes of
      cows in negative energy balance are subsequently discussed. Finally, possible
      relationships between udder defense and physiological changes during negative
      energy balance, especially hyperketonemia, are reviewed. The three stages of an
      acute phase of udder defense are: (1) immediately eliminating invading pathogens
      by phagocytes, (2) releasing inflammatory substances, especially
      chemoattractants, and (3) migration of polymorphonuclear leukocytes into the
      infected udder. Leukocytes from hyperketonemia subjects show a lower capacity of
      the phagocytic defense mechanism. In addition, the phagocytic and bactericidal
      capacities of neutrophils are reduced when these cells are acting in the presence
      of high concentrations of ketone bodies. Lower amounts of cytokine production
      after bacterial infection are observed in ketotic subjects. The chemotactic
      capacity of blood leukocytes is impaired in leukocytes obtained from ketotic
      cows. Lower numbers of blood leukocytes are observed in ketotic cows. In
      conclusion, the impairment of the udder defense mechanism in negative energy
      balance cows seems related to hyperketonemia.

PMID- 10958242
TI  - [Bacterial enterotoxin receptors].
AB  - Bacterial enterotoxin receptors. Enteric bacterial toxins display a great
      diversity in their structure, molecular weight and mechanism of action. The
      interaction of enterotoxins with the intestinal mucosa either leads to a direct
      effect on the cell membrane or an effect on signal transduction within eukaryotic
      cells. However, before a toxin can affect a cell, it must after its secretion by
      a microorganism, recognise and bind to a specific surface molecule, its receptor.
      Membrane receptors of bacterial enterotoxins have been identified as protein,
      glycoprotein or glycolipid in nature. The chemical nature of the molecules acting
      as receptors is crucial and during evolution they have been carefully selected.
      Some toxins, after their interaction with a receptor molecule, will transduce a
      signal across the cell membrane while remaining at the cell surface. Other
      toxins, after this initial binding step with a receptor, will be internalised.
      Others can form pores leading to leakage of cellular components and cell lysis.
      Receptors that have been identified often comprise a saccharidic chain that is
      directly involved in the recognition and binding of the toxin. Today, models
      explaining toxin-receptor interactions are more complex, including multistep
      events. This review summarises the knowledge of the interactions between
      bacterial toxins and membrane receptors present on intestinal mucosa.

PMID- 10958243
TI  - A RT-PCR assay for the rapid recognition of border disease virus.
AB  - A reverse transcription--polymerase chain reaction (RT-PCR) method was developed
      for the specific detection of border disease virus (BDV), using the primers PBD1
      and PBD2 flanking a 225 bp DNA fragment, selected from the 5'noncoding region of
      the pestivirus genome. In tests on 70 pestiviruses it was shown to be BDV
      specific. A closed, one-tube nested RT-PCR method employing general pestivirus
      outer primers (324 and 326), and the same BDV-specific inner primers (PBD1 and
      PBD2) in conjunction with a BDV-specific fluorogenic TaqMan probe also detected
      only BDV and was more sensitive. BDV-specific RT-PCR was used in combination with
      a PCR specific for bovine viral diarrhoea virus type 2 (BVDV2) to ascertain
      whether virus stocks contained mixtures of BDV and BVDV2. It was shown that the
      ovine pestivirus strains 175375 and 59386 were originally BDV, but after
      subculture had become contaminated with BVDV2. This explains a previously
      reported discrepancy in the genetic typing of 59386. Although the BDV-specific RT
      PCR can also detect BDV in clinical samples, the assay is likely to be most
      useful for the rapid typing of laboratory pestivirus strains.

PMID- 10958244
TI  - Ultrastructural glomerular changes in experimental infection with the classical
      swine fever virus.
AB  - Ultrastructural studies of glomerular changes were performed on 16 pigs
      experimentally infected with a highly virulent strain of the classical swine
      fever virus. Our observations revealed the thickening of glomerular basement
      membranes, swelling of endothelial cells and cytoplasmic vacuolization within
      podocytes containing abundant viral particles. An early viral infection of
      podocytes was suggested as the cause of selective swelling of the foot processes
      of these cells with the consequent obliteration of the glomerular urinary spaces.
      To our knowledge this is the first report of ultrastructural evidence of
      classical swine fever virions infecting glomerular podocytes.

PMID- 10958245
TI  - Chirality and its implications in transdermal drug development.
AB  - Today more than 50% of marketed drugs are chiral. It has been well recognized
      that the stereochemistry of chiral drugs has a major influence on their
      pharmacological, pharmacokinetic, and toxicological actions. Studies on
      enantiomeric differences in the percutaneous permeation of chiral compounds have
      been actively pursued in recent years. Stratum corneum, the rate-limiting barrier
      in transdermal permeation, is made up of keratin and ceramide, which could
      potentially provide chiral environment. Transdermal delivery is often facilitated
      by the presence of penetration enhancers, which act primarily by altering the
      diffusion by disrupting the highly ordered membrane structure or by affecting the
      partitioning behavior of the diffusant molecules. Enantioselective permeation was
      observed with some chiral excipients including terpene enhancers. While studies
      on crystalline structures of pure enantiomers and racemates are helpful in
      understanding the basis for differentiation of physicochemical properties,
      prediction and control of permeability of enantiomers and racemates based on the
      physicochemical characteristics would be highly beneficial. The flux
      characteristics of enantiomers and racemates appear to be dependent upon their
      thermodynamic properties. Such analyses have a predictive value and are useful in
      the transdermal drug product development of chiral molecules. While the decision
      to market either an individual enantiomer or racemate lies strictly under the
      control of the sponsors, the guidance of the Food and Drug Administration is very
      helpful. This review presents an overview of the skin structure and transport and
      a concise review of enantioselective permeation with or without chiral enhancers.
      Regulatory perspectives on chiral drug product development are also discussed.

PMID- 10958246
TI  - Polysaccharides for vascular cell targeting.
AB  - Carbohydrate structures are involved in numerous biological activities such as
      inflammation, and cell adhesion/migration/proliferation. This gives the rationale
      for the design of vascular targeted drug delivery systems bearing sugar moieties.
      For the imaging and treatment of vascular diseases, an overview is presented with
      polysaccharides targeting vascular components. After a general description of the
      vasculature and the main blood components, a special emphasis is placed on
      carbohydrate-based molecules, such as heparin/heparan sulfate, and carbohydrate
      binding proteins, such as selectins found in the vascular system. The methods
      using heparin and heparin analogs in delivery systems applied to vascular
      components are then described.

PMID- 10958247
TI  - Targeted gene delivery: a two-pronged approach.
AB  - The success of gene therapy relies on the ability of gene delivery systems to
      selectively deliver therapeutic genes to a sufficient number of target cells
      yielding expression levels that impact the diseased state. The gene delivery
      systems can be divided into two classes: viral and nonviral (or plasmid DNA
      based). The present gene delivery technology being used in clinics today can be
      considered first generation, in that they possess the ability to transfect or
      infect target cells through their inherent chemical, biochemical, and molecular
      biological properties. Relying on these sole properties, however, limits
      therapeutic applications. Expansion of therapeutic applications or increased
      effectiveness of current therapies can be achieved by increasing the number of
      cells and cell types susceptible to gene transfer. This can be achieved through
      physical targeting and molecular biological targeting. Physical targeting relies
      on the attachment to the delivery vehicle of ligands that bind to cell surface
      receptors unique to the target cells. Molecular biological targeting refers to
      selective expression of the therapeutic gene by the target cell through the use
      of selective promoters. Selective expression can be further achieved by the use
      of expression systems controlled by extrinsic induction molecules. This review
      will describe in detail the advances that have been made in each of these areas
      of gene targeting.

PMID- 10958248
TI  - Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere
      mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety
      like behavior: study 3--the effects on amygdala efferent physiology of block of
      NMDA receptors prior to injection of FG-7142 and its relationship to behavioral
      change.
AB  - The findings of this study support the hypothesis that N-methyl-D-aspartate
      (NMDA) receptors mediate the initiation of long-term potentiation (LTP) and
      behavioral changes induced by the anxiogenic beta-carboline, FG-7142. Unlike
      previous work, this study examined the effects of FG-7142 on LTP of amygdala
      efferents in both hemispheres. 7-amino-phosphono-heptanoic acid (AP7), a
      competitive NMDA receptor blocker, given prior to administration of FG-7142,
      prevented LTP in amygdala efferent transmission to the medial hypothalamus and
      periacqueductal gray (PAG). When given FG-7142 alone, cats showed lasting
      behavioral changes accompanied by LTP in all pathways studied. Duration of LTP,
      and its relationship to behavioral change, depended on the pathway and the
      hemisphere of the pathway. Correlation and covariance analyses indicate that LTP
      in the left amygdalo-ventromedial hypothalamic pathway mediates initiation, but
      not maintenance, of increased defensiveness. This finding replicates previous
      work. A new finding is that increased local excitability in the right basal
      amygdala (reduced threshold for evoked response), and LTP in the right amygdalo
      PAG pathway, may be important for maintenance of increases in defensive behavior.
      Furthermore, the effects of flumazenil, a benzodiazepine receptor antagonist, on
      behavior and physiology single out the importance of right amygdalo-PAG LTP as a
      critical mediator of increased defensiveness. Flumazenil reversed the increase in
      defensiveness produced by FG-7142 in a drug-dependent manner as described in
      Adamec (1998a). Moreover, flumazenil reversed LTP only in the right amygdalo-PAG
      pathway. The findings of the present study suggest that response to FG-7142 may
      be a useful model of the effects of traumatic stressors on limbic system function
      in anxiety, especially in view of the recent data in humans implicating right
      hemispheric function in persisting negative affective states.

PMID- 10958249
TI  - Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic
      startle response in man.
AB  - Experiments with animals have shown that D2 dopamine (DA) receptors are involved
      in prepulse inhibition of the acoustic startle reflex (suppression of the reflex
      response evoked by a loud sound by prior presentation of a low-intensity
      stimulus). The present experiment attempted to extend this observation to man.
      Twelve healthy males (18-30 years), screened for normal hearing thresholds,
      participated in four sessions in which they received oral doses of placebo,
      bromocriptine 1.25 mg (a D2 receptor agonist), haloperidol 3 mg (a D2 receptor
      antagonist) and combined treatment with bromocriptine 1.25 mg+haloperidol 3 mg,
      according to a balanced double-blind protocol. Thirty-minute electromyographic
      recordings from the orbicularis oculi muscle of the right eye were carried out
      120 min after ingestion of haloperidol and/or 90 min after ingestion of
      bromocriptine. Subjects received 36 40-msec sound pulses (115 dB), separated by
      variable intervals (mean 25 sec); in 24 of the trials the pulse was preceded by a
      40-msec prepulse (75 dB in 12 trials and 85 dB in 12 trials; prepulse-pulse
      interval, 120 msec). The amplitude of the startle response was not significantly
      altered by any of the active treatments. Under the placebo condition, both 75-
      and 85-dB prepulses inhibited the startle response. Bromocriptine significantly
      attenuated this prepulse inhibition; haloperidol also produced a small but
      statistically significant attenuation of prepulse inhibition. Haloperidol
      significantly antagonized the attenuation of prepulse inhibition produced by
      bromocriptine. Neither drug altered self-rated alertness, physiological finger
      tremor, systolic or diastolic blood pressure or salivation. Bromocriptine
      significantly suppressed and haloperidol significantly elevated serum prolactin
      levels, these changes being absent when the two drugs were given in combination.
      The results provide evidence for the involvement of D2 DA receptors in prepulse
      inhibition of the startle reflex in man.

PMID- 10958250
TI  - Mood improvement in 'normal' volunteers.
AB  - To test the hypothesis that clomipramine is effective in improving subthreshold
      non-specific symptoms in subjects without any established psychopathology, we
      conducted a double-blind, cross-over controlled trial of clomipramine (oral doses
      of 10-40 mg/day) and propanteline (active placebo) for 5 weeks in nine normal
      volunteers. Four other subjects completed the first part of the trial. These
      subjects were selected from 275 respondents to newspaper and radio requests for
      subjects who considered themselves as normal but were unhappy about their usual
      moods. They did not reach cut-off scores in the Self-Report Questionnaire and did
      not meet diagnostic criteria for any lifetime or current ICD-10 or DSM-III-R
      condition, as assessed by an open psychiatric interview and the Schedules for
      Clinical Assessment in Neuropsychiatry. Despite the small sample and the low
      level of initial symptomatology, both subjects and observers consistently
      detected significant improvements with clomipramine in a number of assessments of
      mood, notably decreased irritability and anxiety. This controlled trial suggests
      that it is possible to improve subclinical complaints through
      psychopharmacological agents, raises questions about the mechanisms of their
      action and discusses their implications.

PMID- 10958251
TI  - Repeated administration of fluoxetine, desipramine and tranylcypromine increases
      dopamine D2-like but not D1-like receptor function in the rat.
AB  - We tested the effect of repeated treatment (twice daily for 14 days) of rats with
      the antidepressant drugs fluoxetine, desipramine and tranylcypromine, on the
      behavioural response to the non-selective dopamine (DA) receptor agonist,
      apomorphine, the D1-like receptor agonists, SKF 38393 and SKF 81297 and the D2
      like receptor agonists, RU 24213 and quinpirole. Agonist-induced behaviour was
      monitored by automated activity meters and direct observation using a checklist
      scoring method. Fluoxetine, desipramine and tranylcypromine enhanced (albeit to a
      varying degree) the behavioural responses to apomorphine (0.75 mg/kg, s.c.),
      quinpirole (0.25 mg/kg, s.c.) and RU 24213 (0.75 mg/kg, s.c.). In contrast,
      fluoxetine, desipramine and tranylcypromine did not increase the behavioural
      responses to SKF 38393 (7.5 mg/kg, s.c.) and SKF 81297 (0.5 mg/kg, s.c.).
      Finally, fluoxetine, despiramine and tranylcypromine did not modify the
      behavioural responses to the concomitant administration of SKF 38393 (7.5 mg/kg,
      s.c.) and quinpirole (0.25 mg/kg, s.c.). Our data suggest that repeated
      administration of fluoxetine, desipramine and tranylcypromine increases central
      DA D2-like but not D1-like receptor function.

PMID- 10958252
TI  - Dopamine release in the nucleus accumbens and latent inhibition in the rat
      following microinjections of a 5-HT1B agonist into the dorsal subiculum:
      implications for schizophrenia.
AB  - Microinjection of a serotonergic 5-HT1B agonist (S-CM-GTNH2, 3 microg/l) into the
      dorsal subiculum (DS) induced long-lasting increases in dopamine (DA; +58%),
      dihydroxyphenylacetic acid (DOPAC; +15%) and homovanillic acid (HVA; +31%),
      without changing extracellular levels of the serotonin metabolite 5
      hydroxyindoleacetic acid (5-HIAA), measured by microdialysis in freely moving
      rats in the shell area of the nucleus accumbens (n. acc). Perfusion of a
      glutamate-N-methyl-D-aspartate (NMDA) receptor antagonist (MK 801, dizocilpine,
      10 microM) through the dialysis probe in the n. acc induced similar long-lasting
      increases in DA and DOPAC, whereas the glutamate-quisqualate/kainate receptor
      antagonist (CNQX, 50 microM) had no effect. In the presence of dizocilpine in the
      n. acc, microinjection of S-CM-GTNH2 into the DS could still increase DOPAC and
      HVA, but DA levels were not further changed, whereas in the presence of CNQX,
      microinjection of S-CM-GTNH2 into the DS still increased not only DOPAC and HVA,
      but also DA levels in a way similar to that in the absence of glutamate
      antagonist. Therefore, activation of 5-HT1B receptors located in the DS increases
      the release of DA in the n. acc, presumably via the glutamatergic projection to
      this structure and acting through NMDA receptors in it. This implies either the
      suppression of a tonic indirect inhibitory influence and/or stimulation of a
      phasic excitatory effect of glutamate. Disruption of latent inhibition (LI) has
      been suggested as a model for a cognitive deficit in schizophrenia
      (hyperattention to irrelevant stimuli) and is usually associated with an increase
      in DA release in the n. acc. However, s.c. injection of RU 24 969 (0.5 mg/kg), a
      mixed 5-HT1A-5-HT1B agonist, which was previously shown to increase DA release in
      the n. acc, left LI unchanged. Moreover, bilateral microinjections of S-CM-GTNH2
      into the rat DS tended to potentiate LI, in spite of the increase in DA in n. acc
      demonstrated here. It is concluded that not all increases in DA release in the n.
      acc are functionally equivalent. Sensitization of receptors or impulse-dependent
      increase in DA release might be necessary to disrupt LI. The possible role of
      altered serotonergic transmission, through h5-HT1B receptors (human homologue of
      the rat 5-HT1B receptors) located in the DS, in acute schizophrenia needs to be
      further investigated.

PMID- 10958253
TI  - The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in
      the rat elevated plus-maze test, but not in the social interaction test.
AB  - The effects of the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl
      ester (L-NAME) were investigated in two animal models of anxiety: the elevated
      plus-maze and the social interaction test. In the elevated plus-maze, L-NAME
      (12.5-50 mg/kg) had an anxiogenic-like profile as indicated by dose-dependent
      reductions in the time spent on the open arms, open arm entries, the percentage
      of open arm entries and head dips, but there was no significant effect on the
      number of stretch attend postures. In contrast, L-NAME (12.5-50 mg/kg) failed to
      modify time spent in social interaction but did reduce a measure of vertical
      activity. The differential effects of L-NAME in the two anxiety paradigms are
      discussed.

PMID- 10958254
TI  - A randomized, double-blind, parallel-group comparison of venlafaxine and
      clomipramine in outpatients with major depression.
AB  - A multicentre, randomized, double-blind study was conducted to compare the safety
      and antidepressant efficacy of venlafaxine and clomipramine in 102 outpatients
      with major depression. The patients received either venlafaxine or clomipramine
      at a dose titrated from 50 mg to a maximum of 150 mg/day during the first 2 weeks
      of treatment. Treatment was continued for up to 43 days. Montgomery Asberg
      Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D)
      scores decreased significantly (p < or = 0.05) from baseline in each treatment
      group but were not significantly different between groups. Response rates on the
      MADRS and HAM-D were 62% and 59%, respectively, with venlafaxine and 54% and 43%,
      respectively, with clomipramine. Treatment-emergent study events were the primary
      reason for withdrawal in only 13% of venlafaxine-treated patients and 20% of
      clomipramine-treated patients. On questionnaires, the incidence of
      anticholinergic-type events was 60% with venlafaxine and 68% with clomipramine.
      However, significantly (p = 0.043) more patients in the clomipramine group
      reported multiple anticholinergic events than in the venlafaxine group. In the
      clomipramine group, mean ventricular heart rate increased significantly (p =
      0.003) and mean systolic blood pressure decreased significantly (p = 0.028) from
      baseline, but no clinically significant electrocardiographic changes were
      observed. These results confirm the efficacy and safety of venlafaxine in the
      treatment of outpatients suffering from major depression.

PMID- 10958255
TI  - Nicotine potentiates sulpiride-induced catalepsy in mice.
AB  - The effects of nicotine on sulpiride-induced catalepsy in mice were investigated.
      Sulpiride (12.5-100 mg/kg) induced a low degree of catalepsy in mice which was
      dose dependent. Nicotine (0.0001-1 mg/kg) caused an even lower degree of
      catalepsy. When the drugs were co-administered a much higher cataleptogenic
      response was obtained. The potentiation of the effect of sulpiride by nicotine
      was elicited by 0.5 mg/kg or higher doses of the drug. The central nicotinic
      receptor antagonist mecamylamine (1-3 mg/kg) and the peripheral antagonist
      hexamethonium (5 and 10 mg/kg) decreased the response induced by the combination
      of nicotine and sulpiride. Higher doses of the cholinoceptor antagonist atropine
      (10 mg/kg) also reduced the catalepsy induced by the drug combination. It is
      concluded that nicotine potentiates sulpiride-induced catalepsy through
      activation of cholinergic mechanism(s) and that the central nicotinic mechanism
      mediates nicotine's action.

PMID- 10958256
TI  - Haematological safety of antipsychotic drugs.
AB  - Many clinicians have become concerned about the safety of new antipsychotics
      particularly in view of the association of agranulocytosis with clozapine and of
      aplastic anaemia with remoxipride. The Committee on Safety of Medicines and
      Medicines Control Agency 'yellow card' post-marketing surveillance data were
      analysed for reports of haemopoietic disorders with the 16 antipsychotics in
      common use. Corrections for relative risk were made in three separate ways: (i)
      control for degree of use, using Northern Ireland prescribing data for 1995; (ii)
      percentage of total reports from 1963 to 1996; and (iii) examination of the first
      5 years' post-marketing data only. After clozapine and remoxipride the highest
      risks of haemopoietic reactions appeared to be associated with the aliphatic
      phenothiazine derivatives thioridazine and chlorpromazine. There is therefore no
      evidence of any increased risk with high-potency drugs such as haloperidol or
      pimozide or with the newer drugs such as sulpiride or risperidone. Continued
      vigilance, however, is necessary as more new atypicals become available and begin
      to be widely prescribed.

PMID- 10958258
TI  - The SSRI discontinuation syndrome.
AB  - A characteristic selective serotonin reuptake inhibitor (SSRI) discontinuation
      syndrome appears to exist. It is usually mild, commences within 1 week of
      stopping treatment, resolves spontaneously within 3 weeks, and consists of
      diverse physical and psychological symptoms, the commonest being dizziness,
      nausea, lethargy and headache. SSRI reinstatement leads to resolution within 48
      h. A transient stage of serotonin dysregulation appears central to causation with
      pharmacokinetic and pharmacodynamic differences accounting for the variation in
      incidence between the SSRIs. Discontinuation reactions are clinically relevant
      due to the associated morbidity, the potential for misdiagnosis and inappropriate
      treatment and because they may impair future antidepressant compliance. To
      minimize incidence, SSRIs, like other antidepressants, should be withdrawn
      gradually. Provisional diagnostic criteria for the SSRI discontinuation syndrome
      are proposed. Prospective studies are required to investigate the syndrome,
      particularly its effects on patient care.

PMID- 10958257
TI  - Monoaminergic synapses and schizophrenia: 45 years of neuroleptics.
AB  - In 1952 Delay and Deniker introduced the first antipsychotic, chlorpromazine,
      into the treatment of mental patients. They subsequently defined the word
      'neuroleptic' to describe drugs as different as reserpine and chlorpromazine
      which seemed to have similar effects on the mental life of patients. In the 1960s
      the hypothesis was developed, mainly due to Carlsson, that the principal mode of
      action of neuroleptics was to interfere with synaptic transmission mediated by
      dopamine (DA) in the brain. This concept was given substantial credence with the
      discovery by Seeman and Snyder in the 1970s that many of the neuroleptics acted
      as DA receptor blockers. Subsequently two different classes of DA receptor were
      defined on the basis of their coupling to adenylate cyclase by Kebabian. In the
      1980s molecular biology led to the cloning of five different DA receptors, and at
      the end of this period vanTol and his colleagues cloned the D4 DA receptor, which
      has been of considerable interest in the 1990s as it is greatly elevated in the
      brains of schizophrenics. This historical review ends with a consideration of the
      possibility that in addition to DA receptors, serotonin and perhaps other
      transmitter receptors are involved in the aetiology of schizophrenia.

PMID- 10958259
TI  - Acute and longer-term effects of risperidone in a case of first-episode catatonic
      schizophrenia.
AB  - This case report documents the response of a young, first-episode, neuroleptic
      naive male with severe catatonic schizophrenia to the novel antipsychotic,
      risperidone. Initial assessments included the Positive and Negative Syndrome
      Scales, Global Assessment of Function and the Extrapyramidal Symptom Rating
      Scale. These were repeated at discharge from hospital and during a 3.5 year
      outpatient follow-up. Neuroimaging (computed tomography, magnetic resonance
      imaging and single photon emission tomography) along with electroencephalogram
      and laboratory examinations were completed. Response to risperidone was prompt,
      dramatic and sustained over the follow-up period. Possible neurochemical brain
      mechanisms resulting in catatonia and the role of serotonin/dopamine antagonists
      such as risperidone are discussed. No other literature on the effect of
      risperidone in the treatment of severe catatonic schizophrenia in a first-episode
      patient has been reported.

PMID- 10958260
TI  - A prospective naturalistic study of 326 panic-agoraphobic patients treated with
      antidepressants.
AB  - OBJECTIVE: How far the results of randomized controlled studies apply to everyday
      care cannot be judged without regular measurements of outcomes in daily practice.
      We report on systematic data from a 3-year naturalistic prospective study on
      panic disorder-agoraphobic (PDA) patients treated with antidepressants in a
      setting of routine clinical practice. Our aim is to describe the evolution of PDA
      in relation to the treatments employed, and to explore demographic and clinical
      characteristics that might be predictive of outcome. METHODS: 326 DSM-III-R PDA
      patients treated with antidepressants in a setting of routine clinical practice
      were included in a 3-year naturalistic prospective study. We utilized structured
      and semi-structures instruments, including the Structured Clinical Interview for
      Diagnosis and the Longitudinal Interview Follow-up Examination. The main
      antidepressants used were imipramine (39%), clomipramine (28.5%) and paroxetine
      (23.3%); only 9% of patients received other antidepressants. RESULTS: 147
      patients (45.1%) stayed on medication throughout the entire period of the follow
      up. Of those who interrupted the treatment, 38% stayed in remission. The
      probability of achieving at least one remission during the 3-year follow-up
      period was 96.5% for PD and 95.9% for Agoraphobia. Relapses after a period of at
      least 2 months of complete remission were also common, and the probability of
      presenting at least one relapse during the 3-years follow-up period was 67.1% for
      PD and 39% for Agoraphobia. The longest period of remission of PD is associated
      with low severity, medium-lasting course in patients with an onset of the illness
      in young adulthood. Less severe agoraphobia associated with moderately severe
      panic attacks appears to confer a better control of phobic behavior. All three
      major drugs were reasonably well tolerated (only 9% dropped out because of side
      effects), with sexual dysfunction and increased appetite being the most common
      side effects at the last evaluation; in the first phase of the treatment
      anticholinergic effects and jitteriness were more common with TCAs. CONCLUSION:
      Both classical antidepressants and paroxetine emerge as a useful treatment in the
      long-term management of PDA; paroxetine appears particularly useful in PDA
      patients because it was significantly less likely to induce jitteriness, thereby
      reducing barriers to compliance.

PMID- 10958261
TI  - Acute stress induced modifications of calcium signaling in learned helpless rats.
AB  - Previous reports have demonstrated reduced elevations of free intracellular
      calcium concentration in blood cells of depressed patients after various stimuli.
      Therefore, a disturbance of intracellular calcium (Ca2+) homeostasis has been
      postulated to be involved in the pathophysiology of mood disorders. It was the
      aim of the present study to investigate whether Ca2+ signaling was affected in
      spleen T-lymphocytes of rats submitted to a learned helplessness paradigm, an
      animal model of depression with a high level of construct, face and predictive
      validity. In addition, we tested for effects of acute stress on the Ca2+
      signaling in helpless rats, as compared to non-stressed rats. It was found that
      mitogen-induced Ca2+ signaling only tended to be reduced in helpless rats.
      However, when helpless rats were submitted to acute immobilization stress, Ca2+
      signaling appeared to be significantly blunted, whereas the same stressor did not
      affect Ca2+ signaling in the non-helpless control rats. These acute stress
      induced differences in Ca2+ signaling were not paralleled by a differential
      increase in plasma corticosterone. It is hypothesized that blunted Ca2+
      signaling, as assessed in spleen T-lymphocytes of helpless rats, may be a
      correlate of the increased vulnerability of helpless rats to acute stressors.

PMID- 10958262
TI  - Epidemiological evidence for a low abuse potential of zolpidem.
AB  - The abuse risk of new non-benzodiazepine hypnotics such as zolpidem has been
      discussed in a number of recent publications. We performed a Medline analysis
      which showed that, to date, 15 cases of abuse or dependence have been published.
      In 6 patients, the abuse was secondary to other forms of abuse or dependence.
      Other data from medical statistics and pharmacoepidemiological studies suggest
      the abuse potential of zolpidem to be much lower than that of other hypnotics. We
      conclude that zolpidem is a relatively safe drug compared to conventional
      hypnotics. Patients with other substance abuse histories may be considered as
      risk patients for later abuse of zolpidem.

PMID- 10958263
TI  - Recruitment of depressive patients for a controlled clinical trial in a
      psychiatric practice.
AB  - Attempts were made to recruit moderately depressed patients to a randomized
      double-blind study with a new serotonergic-noradrenergic antidepressant in a
      psychiatry specialist's practice. Although 216 patients consulting a psychiatrist
      for depression were screened, none were suitable for recruitment into the study.
      The most common causes of exclusion were severity of depression (n = 199, 92.1%),
      concomitant treatment with other psychotropic drugs (n = 124, 57.4%) and pre
      treatment with an SSRI or MAO-inhibitor (n = 97, 44.9%). On average, there were
      3.4 criteria per patient that resulted in exclusion from the study. The
      difficulties in recruiting patients demonstrate that psychopharmacological
      studies with the usual inclusion and exclusion criteria are hardly practicable in
      an office-based psychiatric practice. Furthermore, the question to what extent
      results from studies performed under restrictive inclusion and exclusion criteria
      are applicable to routine care must also be put.

PMID- 10958264
TI  - A possible case of lithium intoxication mimicking Creutzfeld-Jakob syndrome.

PMID- 10958265
TI  - Akathisia masked by hypokinesia.
AB  - Here, we will discuss the concept of subjective akathisia and present a patient
      case. Our patient was suffering from neuroleptic-induced hypokinesia and
      akathisia at the same time. The typical motor manifestations of akathisia were
      masked by hypokinesia, which made the diagnosis difficult. However, the
      subjective symptoms of akathisia were evident and distressing. Although not
      observable to bare eye, the pathognomonic pattern of motor activity detected in
      akathisia was demonstrated by actometric recording. Changing the conventional
      neuroleptic to an atypical one brought relief to the subjective symptoms of
      akathisia and hypokinesia, while the motor activity was clearly diminished in
      actometric recording. Actometric recording may be useful in diagnosing akathisia
      masked by hypokinesia, but the typical subjective symptoms of akathisia should
      not be ignored, even when actometry is not available to demonstrate the missing
      motor component of akathisia. Not only akathisia defined by DSM-IV but also
      subjective akathisia should be adequately treated to relieve the subjective
      distress, and to diminish the unfavorable effects on psychotic symptoms,
      behavior, and drug compliance.

PMID- 10958266
TI  - Suicide attempt by pure citalopram overdose causing long-lasting severe sinus
      bradycardia, hypotension and syncopes: successful therapy with a temporary
      pacemaker.
AB  - In few cases, pure citalopram overdose at doses above 600 mg showed electro
      cardiographic changes with prolonged QT intervals and sinus bradycardia gradually
      resolving within 12-24 hours after intoxication. We report on a 32-year-old
      patient with borderline personality disorder (BPD) who ingested a total of 800 mg
      citalopram to attempt suicide due to an interpersonal disappointment. She
      developed severe sinus bradycardia with a minimal pulse rate of 41/min within
      about 4 hours after intoxication lasting up to six days during intensive care
      unit (ICU) treatment. Further, hypotension and syncopes occurred. No QT interval
      prolongations were recorded. To our knowledge, this is the first case report of
      pure citalopram overdose-induced long-lasting sinus bradycardia associated with
      severe hypotension and intermittent syncopes that required therapy with a
      temporary pacemaker.

PMID- 10958267
TI  - Is clozapine useful in schizophrenic patients with concomitant chronic
      inflammatory disease?

PMID- 10958268
TI  - Risperidone-induced tardive dyskinesia.

PMID- 10958269
TI  - Permanent pacing-aid to carry out long-term lithium therapy in manic patient with
      symptomatic bradycardia.

PMID- 10958270
TI  - Heterogeneity of myocardial wall motion and thickening in the left ventricle
      evaluated with quantitative gated SPECT.
AB  - BACKGROUND: Global and regional ventricular function may be evaluated by using
      gated myocardial perfusion single photon emission computed tomography (SPECT).
      This study investigated two parameters of regional contraction of the left
      ventricle, segmental wall motion (WM) and wall thickening (WT), to determine
      their similarity and disparity in each myocardial segment in patients with normal
      myocardial perfusion. METHODS AND RESULTS: Thirty-five patients with normal
      myocardial perfusion and cardiac function (mean left ventricular ejection
      fraction, 62.6%+/-8.8%) were included in this study. A 1-day stress/rest protocol
      was used as a means of acquiring technetium 99m (Tc-99m) sestamibi gated SPECT
      protocol for each patient. A commercially available software package for
      quantitative gated SPECT (QGS) was used to generate cine loop three-dimensional
      surface display and SPECT images. The left ventricle was divided into 9 segments
      to score WM and WT (on a scale of 0 to 4, with 0 being normal and 4 being
      severely reduced) by 6 independent observers. The WM score was significantly
      higher than the WT score in the septum, whereas the WM score was lower than the
      WT score in the inferior segment. Similar WM and WT scores were observed in the
      remaining segments. CONCLUSIONS: Heterogeneous myocardial WM and WT were observed
      by using QGS software. These findings suggest that different criteria are
      required in each segment to evaluate segmental WM and WT by means of gated
      myocardial perfusion SPECT.

PMID- 10958271
TI  - Accuracy of the automated assessment of left ventricular function with gated
      perfusion SPECT in the presence of perfusion defects and left ventricular
      dysfunction: correlation with equilibrium radionuclide ventriculography and
      echocardiography.
AB  - BACKGROUND: Gated single photon emission computed tomography (SPECT) with
      automated methods allows the quantitative assessment of left ventricular function
      and perfusion; however, its accuracy must be defined for patients with large
      earlier infarctions and severe rest perfusion defects, in whom the estimation of
      endocardial and epicardial borders might be more difficult, even with automated
      edge-detection techniques. METHODS AND RESULTS: We prospectively compared the
      automated measurements of left ventricular ejection fraction (LVEF) and volumes
      from rest-injected gated Technetium 99m (Tc99m) perfusion SPECT with equilibrium
      radionuclide angiocardiography (ERNA) in 62 patients and the assessment of
      regional function with echocardiography in 22 patients. Forty-six patients had an
      earlier myocardial infarction (mean defect size, 34% of left ventricle; SD,
      12.7%; range, 8% to 56%); 27 patients had large defects (> or = 20% of left
      ventricle; LVEF range, 8% to 75%). LVEF, as determined with Cedars-Sinai software
      (quantitative gated SPECT), correlated well with ERNA (r = 0.941; y = 1.003x +
      1.15; P<.0001; SE of the estimate = 6.3%; mean difference -1.3% for LVEF) in the
      entire study population and in the subgroups of patients with an earlier
      infarction, severe defects, and large infarctions (> or = 20% of the left
      ventricle). A correlation existed between gated SPECT and ERNA volumes (r =
      0.882, y = 1.040x - 14.7, P<.0001 for end-diastolic volume; r = 0.954, y = 1.147x
      - 13.9, P<.0001 for end-systolic volumes with the count-ratio technique), but
      with wider limits of agreement. The exact segmental score agreement between gated
      SPECT and echocardiography for regional function was 79.8% (281 of 352, kappa =
      0.682). CONCLUSIONS: Automated gated SPECT provides an accurate assessment of
      ejection fraction and regional function, even in the presence of an earlier
      myocardial infarction with large perfusion defects and significant left
      ventricular dysfunction.

PMID- 10958272
TI  - Comparison of two three-dimensional gated SPECT methods with thallium in patients
      with large myocardial infarction.
AB  - BACKGROUND: Two different commercially available gated single photon emission
      computed tomography (GSPECT) methods were compared in a population of patients
      with a major myocardial infarction. METHODS: Rest thallium GSPECT was performed
      with a 90-degree dual-detector camera, 4 hours after injection of thallium-201
      (Tl-201; 185 MBq) in 43 patients (mean age, 62+/-12 years) with a large
      myocardial infarction (mean defect size, 33%+/-16%). End-diastolic volume (EDV),
      end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were
      calculated by using QGS (Cedars Sinai) and MultiDim (Sopha Medical Vision
      International, Buc, France). Images were reconstructed by using a 2.5 zoom and a
      Butterworth filter (order, 5; cut-off frequency, 0.20). LVEF was calculated in
      all patients by using equilibrium radionuclide angiocardiography (ERNA). EDV,
      ESV, and LVEF were also measured by using left ventriculography (LVG). RESULTS:
      Compared with LVG, QGS underestimated LVEF by means of an underestimation of mean
      EDV. MultiDim overestimated EDV and ESV. GSPECT EDV and ESV overestimation was
      demonstrated by means of Bland-Altman analysis to increase with left ventricular
      volume size (P<.05). The difference between LVG and GSPECT volumes was
      demonstrated by means of regression analysis to be correlated with infarction
      size. This effect was particularly important with MultiDim (P<.0001). CONCLUSION:
      In Tl-201 GSPECT, LVEF and volume measurements will vary according to the type of
      software used.

PMID- 10958274
TI  - Use of invasive and nuclear stress testing in patients with acute ischemic
      coronary syndromes in a large, urban, university-affiliated hospital.
AB  - BACKGROUND: Several recent studies have suggested a high use of invasive
      procedures after acute myocardial infarction, without a corresponding improvement
      in survival. We assessed the relative use of invasive procedures and nuclear
      cardiac testing during acute coronary syndromes. METHODS AND RESULTS: We examined
      the in-hospital utilization rates of invasive and nuclear stress tests and their
      association with in-hospital mortality in all patients hospitalized with an acute
      coronary syndrome in a single, university-affiliated hospital for 3 years. The
      study cohort consisted of 1704 consecutive patients with acute myocardial
      infarction and 2414 patients with unstable angina pectoris. The utilization rate
      of nuclear stress testing was much lower than that of coronary angiography in
      patients with either acute myocardial infarction (11.9% vs. 73.9%, P<.001) or
      unstable angina (8.5% vs. 79.3%, P<.001). Patients examined with nuclear stress
      testing, as compared with patients examined solely by means of coronary
      angiography, had lower revascularization and in-hospital mortality rates, both
      after acute myocardial infarction (29.2% vs. 70%, P<.001, and 1.5% vs. 9.6%,
      P<.001, respectively) and unstable angina (14.6% vs. 80.6%, P<.001, and 1% vs.
      5.1%, P<.001, respectively). Revascularization guided by means of nuclear stress
      testing had a lower mortality rate than that performed without the benefit of a
      nuclear test, both in patients with acute myocardial infarction (0% vs. 10.5%)
      and in patients with unstable angina (0% vs. 5.9%). CONCLUSION: Noninvasive
      stress imaging was used much less often than coronary angiography in patients
      with acute coronary syndromes. The lower mortality rate of patients examined with
      nuclear stress testing, compared with patients examined solely by means of
      coronary angiography, deserves further study, especially in patients undergoing
      revascularization.

PMID- 10958273
TI  - Postrevascularization recovery of fatty acid utilization in ischemic myocardium:
      a randomized clinical trial of potassium channel opener.
AB  - BACKGROUND: Abnormal fatty acid metabolism persists in hibernating myocardium,
      even after reperfusion. This study was designed to determine whether the K+
      channel opener, nicorandil, improves fatty acid utilization after percutaneous
      transluminal coronary angioplasty (PTCA). METHODS: Patients undergoing elective
      PTCA were randomly assigned to treatment (group N, n = 26) or control groups
      (group C, n = 22). Group N received intracoronary and intravenous nicorandil
      during PTCA. Myocardial fatty acid use and perfusion were quantitatively
      evaluated by means of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid
      single photon emission computed tomography (I-123 BMIPP SPECT) and thallium-201
      (Tl-201) imaging before PTCA, 72 hours after PTCA, and 3 months after PTCA. Left
      ventricular function was also evaluated by means of contrast ventriculography
      before and 3 to 6 months after PTCA. RESULTS: The 1-123 BMIPP defect score in
      group N significantly decreased, from 28%+/-13% to 20%+/-20% after PTCA and to
      18%+/-17% 3 months later. In contrast, the I-123 BMIPP defect score in group C
      increased from 28%+/-20% to 36%+/-15% (P<.05 versus group N) after PTCA, then
      returned to 28%+/-17% (P<.05 versus group N) 3 months after PTCA. Recovery of
      left ventricular function paralleled the recovery of I-123 BMIPP uptake.
      CONCLUSIONS: Nicorandil improves the recovery of myocardial fatty acid
      utilization and cardiac function after PTCA. K(ATP) channel activation may have a
      protective effect during coronary artery occlusion and improve subsequent
      recovery.

PMID- 10958275
TI  - Prognostic value and quality of life in patients with normal rest thallium
      201/stress technetium 99m-tetrofosmin dual-isotope myocardial SPECT.
AB  - BACKGROUND: The prognostic value of normal dual-isotope single photon emission
      computed tomography (SPECT), with technetium 99m-tetrofosmin for the stress
      images, is not well known. Furthermore, thallium-201 cross talk in the Tc-99m
      window may reduce the defect severity of the Tc-99m images. METHODS AND RESULTS:
      In a consecutive series of 610 patients, 246 patients with normal rest and stress
      SPECT images by means of visual semiquantitative analysis were included. The
      patients' pre-test likelihood of coronary artery disease was determined, based on
      age, sex, symptoms, and the results of stress electrocardiography. Quality of
      life was assessed by using a mailed self-administered general quality-of-life
      questionnaire. We compared the mean scores (8 dimensions) of our study population
      with the scores of 1063 control subjects, sampled randomly out of the inhabitant
      register of a Dutch city. The mean follow-up period was 25+/-3 months. Compared
      with the control group, patients in our study scored lower (less perceived
      health) for all dimensions of the SF-36 (P<.05), suggesting a selection of
      symptomatic or otherwise diseased patients. The primary cardiac event rate was
      0.4% per year. The cardiac events occurred in patients with an intermediate-to
      high pre-test likelihood of disease and negative or nondiagnostic exercise
      electrocardiographic results. In a subset of patients with a high pre-test
      likelihood of coronary artery disease (more than 85%), the primary cardiac event
      rate was 0.7% per year. CONCLUSIONS: Patients with normal results on dual-isotope
      myocardial perfusion scintigraphy, performed with Tc-99m-tetrofosmin for the
      stress images, have an excellent prognosis. Furthermore, our results suggest that
      Tl-201 cross talk in the Tc-99m window may be low and functionally and clinically
      unimportant.

PMID- 10958277
TI  - Myocardial sympathetic innervation in the athlete's sinus bradycardia: is there
      selective inferior myocardial wall denervation?
AB  - BACKGROUND: Sinus bradycardia in trained athletes is predominantly a
      manifestation of increased vagal tone, but it is not known whether an alteration
      in the cardiac sympathetic system can contribute to blunted chronotropic
      response. This study assessed the integrity of the sympathetic system in trained
      athletes with sinus bradycardia by means of the iodine-123
      metaiodobenzylguanidine (123I-MIBG) procedure. METHODS AND RESULTS: Fourteen
      athletes with sinus bradycardia and 8 athletes with a normal heart rate were
      explored by means of planar and single photon emission computed tomography MIBG
      studies. The heart/mediastinum ratio, regional myocardial distribution, and
      percent of regional myocardial MIBG uptake were evaluated. The heart/mediastinum
      ratio in athletes with sinus bradycardia was 1.87+/-0.10, and in athletes with a
      normal heart rate, the heart/mediastinum ratio was 1.86+/-0.16 (P = not
      significant). In athletes with sinus bradycardia, the regional distribution of
      MIBG showed an inferior and apical uptake defect in 8 athletes, an inferior,
      apical, and septal defect in 3 athletes, an inferior defect in 1 athlete, and
      normal distribution in 2 athletes (14%). In athletes with a normal heart rate,
      the regional distribution of MIBG showed an apical uptake defect in 3 athletes
      and normal distribution in 5 athletes (63%). The percent of regional MIBG uptake
      in the inferior region was significantly reduced in athletes with sinus
      bradycardia (44%+/-13% vs. 72%+/-11%, P<.01). CONCLUSION: These results show
      severely reduced myocardial MIBG distribution in the inferior region in athletes
      with sinus bradycardia, suggesting selective inferior myocardial wall sympathetic
      denervation, which may be related to increased vagal tone.

PMID- 10958276
TI  - Sustained reduction of exercise perfusion defect extent and severity with
      isosorbide mononitrate (Imdur) as demonstrated by means of technetium 99m
      sestamibi.
AB  - BACKGROUND: The impact of long-acting nitrates on the extent and severity of
      stress-induced myocardial ischemia is not well described, especially after long
      term treatment. METHODS: Forty patients with chronic stable angina and reversible
      ischemia on an exercise stress myocardial perfusion single photon emission
      computed tomography (ex-SPECT) were prospectively studied in a 6-week period. At
      baseline, rest thallium-201/exercise stress technetium 99m sestamibi SPECT was
      performed, followed by treatment with extended-release isosorbide 5-mononitrate
      (5-ISMN, Imdur). Follow-up ex-SPECT was performed 5 days and 6 weeks after the
      initiation of therapy with extended-release 5-ISMN. The exercise treadmill
      testing (ETT) protocol and exercise duration of the follow-up studies were the
      same as that of the baseline ETT. Defect extent and severity were analyzed both
      by means of an automated quantitative method, with CEqual software, and visually,
      with a 20-segment scoring system (which was also used to derive a summed stress
      score [SSS]). RESULTS: In the 6-week study period, significant reductions
      occurred in both the extent and the severity of exercise-induced ischemia by
      means of quantitative SPECT (13.8% [P<.0003] and 12.7% [P<.0003], respectively).
      There was no significant change in these variables between stages 2 (day 5) and 3
      (6 weeks), indicating no development of tolerance to the nitrate effect. Similar
      reductions were noted by means of the visual analysis (SSS reduction of 13.0%
      [P<.002]) in the entire study period. CONCLUSIONS: Patients with chronic-stable
      angina treated with a long-acting nitrate demonstrate improvement in myocardial
      perfusion defect extent and severity in an extended period by means of both
      visual and quantitative analysis of sequential exercise testing to the same rate
      pressure product end point.

PMID- 10958278
TI  - Detection of deep venous thrombosis by DMP 444, a platelet IIb/IIIa antagonist: a
      preliminary report.
AB  - BACKGROUND: We report a method for detection of deep venous thrombosis with a
      technetium 99m-labeled peptide (DMP 444). The N-methyl-arginine-glycine-aspartic
      acid sequence on DMP 444 binds the glycoprotein IIb/IIIa receptor on activated
      platelets (inhibition constant [IC50] for fibrinogen binding = 6 nmol/L).
      METHODS: DMP 444 (23 to 27 mCi) was injected into 11 patients with clinical
      suspicion of deep venous thrombosis, diagnostic confirmation by ultrasound, and a
      positive D-dimer test result. Planar images in the anterior and posterior
      projections were obtained at 10 to 40 minutes, 50 to 80 minutes, and 120 to 150
      minutes after injection. RESULTS: No clinically significant adverse effects were
      noted after DMP 444 administration. One patient (excluded from the analysis)
      withdrew consent, so image acquisition was not complete. By 10 to 40 minutes
      after injection, 8 of 10 patients demonstrated an area of increased activity that
      was clearly related to the abnormality noted on ultrasound. Most patients were
      taking warfarin (Coumadin) and heparin (n = 8) or heparin (n = 1) and warfarin (n
      = 1) alone at the time of the imaging. The average time from onset of symptoms to
      injection of DMP 444 was 5 days (range 1 to 18 days). CONCLUSION: These
      preliminary human studies indicate that DMP 444 is safe and may be of value in
      the diagnosis of deep venous thrombosis.

PMID- 10958279
TI  - Influence of calcium channel inhibitors on the myocardial uptake and retention of
      technetium 99m N-NOET, a new myocardial perfusion imaging agent: a study on
      isolated perfused rat hearts.
AB  - BACKGROUND: Technetium 99m N-NOET is a new myocardial perfusion imaging agent
      currently in phase III clinical trials in Europe. In vitro studies on newborn rat
      cardiomyocytes have shown that calcium inhibitors, such as verapamil or
      diltiazem, inhibit its cellular uptake by 40%. To determine whether such a
      specificity exists ex vivo, we studied the effect of verapamil, diltiazem, and
      nifedipine on the myocardial uptake and retention of Tc-99m N-NOET in isolated
      perfused rat hearts. METHODS AND RESULTS: After a 15-minute baseline period, rat
      hearts were perfused with 0.5 micromol/L verapamil (n = 6), 0.75 micromol/L
      diltiazem (n = 6), or 0.1 micromol/L nifedipine (n = 6) for 10 minutes before the
      injection of a bolus (40 microCi/250 microL) of the tracer. Control hearts were
      perfused with either 1.5 mmol/L calcium (same concentration as in the treated
      groups; n = 7) or 0.75 mmol/L calcium (same contractility as in the treated
      groups; n = 6). Myocardial activity of Tc-99m N-NOET was monitored for 30
      minutes. The functional parameters of the hearts were recorded throughout the
      experiments. Calcium inhibitors induced a 40% to 55% decrease in maximal first
      derivative of left ventricular pressure (dP/dt) (0.0001<P< .001 versus control,
      calcium 1.5 mmol/L). After 30 minutes, tracer retention was 51.6%+/-6.1% injected
      dose (ID)/g and 54.2%+/-10.2% ID/g for control hearts perfused with 1.5 mmol/L
      and 0.75 mmol/L calcium, respectively (P = not significant). Myocardial activity
      of Tc-99m N-NOET was not modified in hearts perfused with verapamil (50.0%+/-4.1%
      ID/g), diltiazem (47.2%+/-8.7% ID/g), or nifedipine (51.7%+/-3.4% ID/g; P = not
      significant versus control hearts perfused with 1.5 mmol/L or 0.75 mmol/L
      calcium). CONCLUSIONS: Verapamil, diltiazem, and nifedipine were not responsible
      for any variations in Tc-99m N-NOET uptake and retention in the isolated rat
      heart model. This might be explained by the binding of the tracer to endothelial
      cells, which do not present voltage-dependent calcium channels.

PMID- 10958281
TI  - F-18 fluoro deoxyglucose SPECT for assessment of myocardial viability.
AB  - Identification of myocardial viability in hypokinetic segments is important in
      patients with ischemic cardiomyopathy because systolic dysfunction improves with
      revascularization. Positron emission tomography (PET) F-18 fluoro deoxyglucose
      (FDG) uptake has been demonstrated as an accurate indicator of metabolically
      active and thus viable myocardium. F-18 FDG single photon emission computed
      tomography (SPECT) has recently been introduced and offers a technically easier
      and less costly alternative to PET imaging for determination of myocardial
      viability. A body of literature demonstrates that F-18 FDG SPECT can reliably be
      performed with SPECT hardware equipped with 511-keV collimators, which provides
      an accurate assessment of myocardial viability. F-18 FDG SPECT offers data
      similar to those offered by F-18 FDG PET and compares favorably with other
      imaging modalities, including rest-redistribution and stress-reinjection thallium
      201 myocardial perfusion imaging, gated technetium 99m SPECT, and low-dose
      dobutamine echocardiography.

PMID- 10958280
TI  - Molecular basis of thrombolytic therapy.

PMID- 10958282
TI  - Reason over reflex in acute ischemic syndromes: the case for a rational
      application of invasive procedures:.

PMID- 10958283
TI  - Monitoring medical management of coronary artery disease: patient selection,
      optimal management, and potential problems for diagnosis.

PMID- 10958284
TI  - Resolution of perfusion defects with antiischemic medical therapy.

PMID- 10958285
TI  - Intersocietal Commission for the Accreditation of Nuclear Medicine Laboratories
      (ICANL) position statement on standardization and optimization of nuclear
      cardiology reports.

PMID- 10958286
TI  - President's message: beyond perfusion imaging.

PMID- 10958287
TI  - Do you need to combine exercise with dipyridamole? Is this your routine practice?
      How do you deal with the reverse redistribution pattern? Is it a clinically
      relevant issue?

PMID- 10958288
TI  - Abdominal aortic aneurysm rupture following endoluminal graft deployment: report
      of a predictable event.
AB  - PURPOSE: To describe the predictability of an abdominal aortic aneurysm (AAA)
      rupture secondary to a type II endoleak following stent-graft exclusion. METHODS
      AND RESULTS: An 81-year-old man with an enlarging AAA underwent endovascular
      repair using an AneuRx aortic stent-graft, but a type II endoleak fed by an
      accessory renal artery was detected at postprocedural computed tomography (CT).
      Surveillance CT scans at 6 and 16 months showed an increase in the aneurysm
      diameter and endoleak volume, but the patient refused advised treatment to close
      the leak. He suffered a fatal aneurysm rupture 24 months after endografting.
      Retrospective analysis of CT data documented progressive aneurysm enlargement
      that correctly predicted the rupture. CONCLUSIONS: Type II endoleaks can lead to
      aneurysm rupture. Three-dimensional (3D) spiral CT angiography offers an
      opportunity to track endoleak volume and the effect of exposure to systemic
      pressure on the aneurysm sac.

PMID- 10958289
TI  - Abciximab in carotid stenting for postsurgical carotid restenosis: intermediate
      results.
AB  - PURPOSE: To report intermediate results of a pilot study in which the
      glycoprotein IIb/IIIa receptor antagonist abciximab was given to patients during
      percutaneous carotid stenting for recurrent internal carotid artery (ICA)
      stenosis. The objective was to prevent procedure-related cerebral embolic events
      and decrease the incidence of recurrent stenosis. METHODS: Sixteen patients (9
      women; mean age 66.5 years, range 39-78) with severe ICA recurrent stenosis
      (>80%) underwent balloon angioplasty and stenting. Before the procedure,
      abciximab was administered intravenously as a bolus (0.25 mg/kg) followed by a 12
      hour continuous infusion (10 microg/min). RESULTS: Fifteen patients received
      stents (14 Wallstent and 1 Strecker); 1 vessel was dilated with only 50%
      improvement in luminal diameter. Two stented arteries had residual stenosis
      (<30%) but satisfactory luminal diameter was achieved in the remaining 13 (81%)
      arteries. There were no neurological ischemic events during or following the
      procedure, nor were there any bleeding or peripheral vascular complications.
      Duplex surveillance studies up to 12 months revealed no significant recurrent
      stenosis in the treated vessels. CONCLUSIONS: The administration of abciximab in
      conjunction with percutaneous revascularization procedures for postsurgical
      carotid artery stenosis may reduce cerebral ischemic episodes. It may also
      attenuate restenosis in the treated artery.

PMID- 10958290
TI  - Transrenal fixation of aortic endografts: intermediate follow-up of a single
      center experience.
AB  - PURPOSE: To examine the fate of the renal ostia following transrenal fixation of
      endovascular aortic stent-grafts. METHODS: Thirty-five patients (29 men; mean age
      75 years) undergoing endovascular repair for abdominal aortic aneurysms (AAAs)
      had transrenal fixation of the uncovered proximal stent due to a short (< 1.5 cm
      long) or conical neck or a periprocedural endoleak. Eighteen (51%) patients were
      hypertensive; 7 (20%) had renal artery stenoses (RAS). Outcome measures included
      blood pressure, serum creatinine, computed tomography, and renal artery duplex
      scans. RESULTS: Two patients with > or = 60% RAS had renal stents placed during
      the endograft procedure; the other 5 RAS patients were normotensive and their
      renal lesions were not treated. Overall technical success was 82.9% (29/35). One
      (2.9%) case was converted due to graft twisting. There were 5 (14.2%) early
      endoleaks. Transient postoperative creatinine elevations were observed in 5
      (14.2%) cases. Over a median 11-month period (range 2-24), no secondary endoleaks
      or silent renal artery occlusions were seen. One normotensive patient with an
      untreated > or = 60% renal lesion developed hypertension and severe stenosis
      (99%) at 4 months; stenting through the interstices of the transrenal stent was
      performed. No disease progression was seen in the other 6 RAS patients.
      CONCLUSIONS: In the intermediate period, transrenal fixation appears to have no
      adverse effects on renal blood flow. Moreover, in patients with no evidence of
      renal disease or preoperative RAS < 60%, it does not precipitate or cause
      progression of renal stenosis. However, patients with preoperatively documented
      RAS > or = 60% are a concern and mandate further study.

PMID- 10958291
TI  - Midterm changes in aortic aneurysm morphology after endovascular repair.
AB  - PURPOSE: To study midterm changes in aortic aneurysm morphology after
      endovascular aneurysm repair. METHODS: Of 94 patients with abdominal aortic
      aneurysms (AAAs) treated with endografts between November 1993 and August 1998,
      84 were available for follow-up. Patients were evaluated preoperatively by spiral
      computed tomography (CT) and aortography; in follow-up, spiral CT scanning was
      performed at 1, 3, and 6 months and semiannually thereafter. Measurements of the
      aneurysm neck diameter, maximum aneurysm diameter, and the distance from the
      lowermost renal artery to the aortic bifurcation were made preoperatively and in
      follow-up. RESULTS: Mean follow-up was 17.5 +/- 1.1 months; 56 (67%) patients
      were followed for 1 year and 28 (33%) for > or = 2 years. There was a median 2-mm
      increase (interquartile range [IQR] 0 to 3) in neck diameter at 18 months.
      However, a > or = 3-mm increase was seen in 18 (46%) of 39 patients examined at
      18 months (median 4 mm, IQR 3 to 4, p = 0.0001). The maximum AAA diameter
      decreased by 9 mm (IQR 4 to 16, p = 0.0003) at 24 months, but after 18 months, no
      further interval decrease was seen. Aneurysms with a persistent endoleak showed
      either increasing or unchanged AAA diameters. There was no change in the renal
      artery to bifurcation distance. CONCLUSIONS: The infrarenal aortic neck appears
      to dilate after AAA endografting, but only in a subset of patients. Shrinkage of
      aneurysms after successful stent-grafting seems to stop after 18 months, implying
      that the only indication of late failure in the absence of endoleak might be
      aneurysm enlargement. Graft-related endoleaks are often associated with an
      increase in aneurysm diameter.

PMID- 10958292
TI  - Aortic stent-grafts in patients with renal transplants.
AB  - PURPOSE: To report the endovascular treatment of abdominal aortic aneurysms (AAA)
      in 2 patients with pelvic renal transplants. METHODS AND RESULTS: Two men with
      multiple comorbidities and pelvic transplant kidneys underwent endovascular AAA
      repair using an aortomonoiliac system with femorofemoral bypass grafting. The
      arterial end-to-side anastomosis in both patients was to the external iliac
      artery. Tapered aortomonoiliac grafts were fashioned from Gianturco Z-stents
      covered with Dacron graft material and implanted with the distal attachment site
      in the iliac system ipsilateral to the transplant kidney arterial anastomosis.
      The body of the stent-graft was reinforcement with a Wallstent in each case
      before the contralateral common iliac artery was occluded and the cross-femoral
      bypass constructed. Both patients recovered uneventfully from the procedure and
      are free of endoleak or other complications related to their aneurysm repair at 7
      and 34 months. CONCLUSIONS: The presence of a pelvic renal transplant in a
      patient undergoing endovascular AAA repair increases the complexity of procedural
      planning and endograft implantation, but a good outcome can be achieved.

PMID- 10958293
TI  - Safety and efficacy of high-dose adenosine-induced asystole during endovascular
      AAA repair.
AB  - PURPOSE: To assess the safety and efficacy of high-dose adenosine administration
      to increase the precision of endovascular abdominal aortic aneurysm (AAA) repair
      using a balloon deployed stent-graft. METHODS: From January 1997 to March 1999,
      98 AAA patients (79 men; mean age 71 years, range 62-91) were treated with
      balloon-expandable stent-grafts under an approved protocol. After placing a
      temporary transvenous ventricular lead or an external transthoracic pacing
      electrode, adenosine (24 mg initially) was administered in an escalating dose
      fashion to induce at least 10 seconds of asystole, during which the proximal
      stent was expanded. RESULTS: Adenosine dosages ranged from 24 to 90 mg (median 24
      mg). Nine (9.2%) self-limiting cardiac events were observed: 2 (2.0%) episodes of
      transient myocardial ischemia, 2 (2.0%) cases of atrial fibrillation requiring
      cardioversion, 1 (1.0%) transient left bundle branch block lasting <10 seconds,
      and 4 (4.1%) prolonged periods of asystole requiring temporary pacemaker
      activation. There were no cases of bronchospasm or worsening obstructive
      pulmonary disease, and no patients required inotropic support after adenosine
      induced asystole. CONCLUSIONS: Cardiac events following adenosine-induced
      asystole are infrequent, mild, and easily treated. The perioperative use of high
      dose adenosine to ensure precise stent-graft placement appears to be a safe
      method of inducing temporary asystole during endovascular aortic repair.

PMID- 10958294
TI  - Embolization of type II endoleaks fed by the inferior mesenteric artery: using
      the superior mesenteric artery approach.
AB  - PURPOSE: To evaluate the use of a superior mesenteric artery (SMA) approach to
      embolize type II endoleaks arising from the inferior mesenteric artery (IMA).
      TECHNIQUE: When reperfusion of the aneurysmal sac via the SMA occurs through the
      IMA, as shown by computed tomography (CT) and angiography, the IMA origin can be
      accessed via the marginal artery or the anastomosis of Riolan. The SMA is
      catheterized with a 5-F catheter, and a coaxial catheter is advanced to the leak
      to deliver 2- to 8-mm-diameter minicoils to embolize the IMA origin and entire
      aneurysmal sac. Embolization usually requires from 1 to 2 hours to complete. In
      our experience with this technique in 11 cases, complications have not occurred,
      and there has been only one very small residual leak that sealed the next day.
      Over a 24.5-month follow-up (range 12-39), the endoleaks have remained sealed
      according to serial color duplex scans. CONCLUSIONS: Successful percutaneous
      treatment of type II endoleak due to IMA inflow can be accomplished using an SMA
      access via the Riolan anastomosis or marginal artery. The procedure appears to be
      safe and has no adverse effects.

PMID- 10958295
TI  - Effort subclavian vein thrombosis: evolution of management.
AB  - PURPOSE: To analyze changes in the management of effort subclavian vein
      thrombosis at our institution. METHODS: Records of 23 patients with effort
      subclavian vein thrombosis treated over a 10-year period were analyzed to compare
      the results of conventional therapy (heparin/warfarin) used in the first half of
      this period to a multimodality treatment strategy (thrombolysis and other
      adjunctive treatment as indicated, e.g., first rib resection,
      angioplasty/stenting, and vein reconstruction). Diagnostic testing included
      duplex ultrasound and venography. All patients had at least 1-year follow-up.
      RESULTS: Eight patients (7 men; mean age 34 years, range 15-54) had conventional
      treatment (group A) and 15 patients (14 men; mean age 36 years, range 17-55) had
      multimodality therapy (group B). Demographics and clinical characteristics were
      comparable for both groups. Initial thrombolysis was achieved in 14 (93%) group B
      patients; 10 received adjunctive treatment to relieve external compression or
      vein stenosis. Four patients had successful first or cervical rib resection and
      scalenectomy, and first rib resection followed by angioplasty/stenting was
      successful in 2. However, angioplasty and stenting alone failed in 2 patients,
      while venous reconstruction was successful in only 1 of 2 cases. Mean follow-up
      was 72 months in group A patients and 59 months in group B. One (13%) group A
      patient and 12 (80%) group B patients demonstrated total venous recanalization
      and symptom resolution (p = 0.003). Overall, clinical resolution (total and
      partial symptom relief) was achieved in 3 (38%) group A patients and 13 (87%)
      group B patients (p = 0.026). CONCLUSIONS: Initial lytic therapy followed by
      adjunctive treatment to relieve external venous compression or venous stenosis is
      effective in treating patients with effort subclavian vein thrombosis.

PMID- 10958296
TI  - Endovascular in situ bypass decreases morbidity and hospital stay following
      infrainguinal arterial reconstruction.
AB  - PURPOSE: To report the early results of endovascular in situ saphenous vein
      bypass (EISVB) using side branch coil occlusion. METHODS: Between September 1997
      and November 1998, 25 patients (15 men; mean age 70.9 years, range 53-85) with
      lower limb ischemia were treated with endovascular femorodistal bypass. The
      saphenous vein was prepared using retrograde valvulotomy and endoscopic
      cannulation with coil occlusion of the side branches. Duplex graft surveillance
      was performed at 1, 3, 6, and 12 months. RESULTS: The 25 EISVB procedures
      consisted of 15 femorodistal popliteal, 7 femorotibial, 2 femoroperoneal, and 1
      femorodorsalis pedis in situ saphenous vein reconstructions. Mean operative time
      was 202 +/- 40 minutes, mean number of side branch coils per case was 5.1 +/-
      1.3, and mean number of incisions per case was 2.9 +/- 0.6. Mean hospital length
      of stay (LOS) was 35 +/- 13 hours (1.4 +/- 0.6 days); 19 (76%) patients were
      discharged on the first postoperative day. Short-term follow-up (mean 6.2 months,
      range 2-15) was notable for 2 graft thromboses and 1 graft stenosis; primary and
      secondary patency rates were 88% and 92%, respectively. Three asymptomatic,
      persistent arteriovenous fistulas discovered on routine duplex were ligated in
      the outpatient setting. Only 1 (4%) minor wound complication was encountered.
      CONCLUSIONS: EISVB provides early patency comparable to conventional in situ
      infrainguinal bypass. Its distinct advantages, however, are the ability to
      minimize incision length with resultant reductions in wound-related
      complications, hospital LOS, and recovery time. EISVB promises to be a useful
      adjunct in the approach to peripheral vascular insufficiency.

PMID- 10958297
TI  - Intravascular ultrasound assessment of iliac stent procedures.
AB  - PURPOSE: To determine whether intravascular ultrasound (IVUS) is more sensitive
      in identifying incomplete stent deployment or mechanical disruption compared to
      angiography. METHODS: Over a 9-month period, 44 patients (25 men; mean age 63
      years, range 36-88) treated for common or external iliac artery stenoses with
      balloon angioplasty and stenting underwent IVUS interrogation following
      completion arteriography. RESULTS: One hundred nine stents were deployed in the
      44 patients. Of these, 29 (27%) stents (in 45% of patients) were found by IVUS to
      be incompletely deployed or to have an associated mechanical disruption despite a
      normal completion arteriogram. Further treatment (repeat dilation or additional
      stenting) was performed in 28 cases; 1 hemodynamically insignificant dissection
      was not treated. Twenty-six (93%) of these interventions were successful as
      determined by IVUS; 2 underexpanded stents did not respond to redilation.
      CONCLUSIONS: Incomplete stent deployment or mechanical problems associated with
      stenting were common in this study, occurring in nearly half of the patients.
      IVUS has clinical utility in identifying incomplete deployment or mechanical
      problems in stents with an increased sensitivity compared to contrast
      angiography.

PMID- 10958298
TI  - Stent implantation for mesenteric bypass graft stenosis.
AB  - PURPOSE: To present a case of symptomatic mesenteric bypass graft stenosis
      treated with Palmaz stent implantation. METHODS AND RESULTS: A 65-year-old man
      with a history of mesenteric ischemia and superior mesenteric artery (SMA)
      occlusion presented with recurrent symptoms 3 years after Dacron graft revision
      surgery for occlusion of a venous aorto-SMA bypass graft. Graft thrombectomy
      revealed a tortuous segment of narrowed graft proximally, and a Palmaz stent was
      deployed across the defect. Adequate flow was restored through the conduit, and
      the patient has remained asymptomatic for 2 years. CONCLUSIONS: Mesenteric
      ischemia is a rare and potentially fatal condition requiring major vascular
      intervention. Revision surgery may be avoided by angioplasty and stent insertion
      across flow-limiting stenoses, even in prosthetic grafts.

PMID- 10958299
TI  - Emergency stent-graft repair of a ruptured hepatic artery secondary to local
      postoperative peritonitis.
AB  - PURPOSE: To describe the use of a stent-graft for emergent repair of life
      threatening hepatic artery hemorrhage. METHODS AND RESULTS: A 57-year-old man
      with a 17-year history of myxoid liposarcoma underwent surgery for a recurrent
      abdominal mass. Multivisceral resection including a Kausch-Whipple procedure with
      an extended right hemicolectomy was performed. Three weeks later, an episode of
      gastrointestinal bleeding prompted surgical repair of the hepatic artery, which
      had been eroded by infection due to a leaking bilioenteric anastomosis. After 3
      weeks of programmed abdominal lavage, bleeding recurred. Angiography documented
      another rupture of the proximal hepatic artery. After an unsuccessful attempt at
      coil embolization, a Hemobahn stent-graft was implanted percutaneously during
      simultaneous cardiopulmonary resuscitation. Hemostasis was secured, and the
      patient recovered. Over the 10-month follow-up, no bleeding or infection has been
      observed at the site of the repair, and flow through the hepatic artery endograft
      remains satisfactory. CONCLUSIONS: Percutaneous stent-graft placement can be
      employed for emergent treatment of visceral artery rupture in patients at high
      risk for conventional surgical repair.

PMID- 10958300
TI  - Endovascular repair of an aortoduodenal fistula.
AB  - PURPOSE: To demonstrate the utility of endovascular stent-graft repair for the
      management of an unusual aortoduodenal fistula. METHODS AND RESULTS: A 23-year
      old man with an aortoduodenal fistula secondary to tumor necrosis was treated
      with a Corvita endoluminal stent-graft after several failed surgical attempts to
      repair the defect. At 2-year follow-up, the patient was clinically and
      radiographically devoid of any evidence of occult stent-graft infection.
      CONCLUSIONS: This case illustrates the usefulness of endovascular repair for the
      treatment of a primary aortoduodenal fistula. Endovascular repair should be
      included in the armamentarium for the management of difficult aortoduodenal
      fistulas.

PMID- 10958301
TI  - Percutaneous treatment of life-threatening congenital arteriovenous malformations
      with the Wallgraft endoprosthesis.
AB  - PURPOSE: To report the percutaneous endovascular repair of massive congenital
      arteriovenous malformations (AVMs) of the right arm complicated by tissue
      ischemia, severe edema, and life-threatening recurrent hemorrhagic episodes.
      METHODS AND RESULTS: A 25-year-old man with a 3-year history of symptomatic upper
      right arm AVMs had been treated unsuccessfully with surgical ligation and coil
      embolization. The arm had become massively enlarged, disfigured, severely
      painful, and unusable, with extension of swelling to the upper chest. Under
      compassionate use as part of an investigational protocol, the AVMs were closed
      with 6 overlapping Wallgraft endoluminal prostheses deployed in the right
      brachial, axillary, and subclavian arteries, preserving the vertebral and distal
      circulations. Unfortunately, the patient suffered numerous pulmonary emboli and
      died 2 days after the procedure. CONCLUSIONS: Percutaneous treatment of massive
      AVMs appears feasible with the Wallgraft endoprosthesis, but optimal
      postprocedural management of such large anomalies should include immediate venous
      filter placement and aggressive anticoagulation therapy with intravenous heparin.

PMID- 10958302
TI  - Primary stenting for chronic total occlusion of the infrarenal aorta.
AB  - PURPOSE: To present a rare case of chronic total occlusion of the infrarenal
      aorta treated with a self-expanding endoluminal stent implanted without
      preliminary dilation. METHODS AND RESULTS: A 68-year-old woman presented with
      severe bilateral buttock and thigh claudication. Angiography revealed total
      occlusion of the infrarenal abdominal aorta and relatively normal iliac vessels.
      Via a right groin puncture and a 9-F sheath, a 14-mm x 5-cm self-expanding
      Wallstent was deployed in the abdominal aorta and expanded with an angioplasty
      balloon. Completion angiography showed successful recanalization of the aorta
      with satisfactory distal flow. Palpable distal pulses were restored, and the
      patient's symptoms were alleviated. She remained asymptomatic until her death
      from a major stroke 11 months after aortic stent implantation. CONCLUSIONS:
      Primary stenting may be considered a viable alternative to conventional surgery
      in selected patients with total infrarenal aortic occlusion.

PMID- 10958303
TI  - A new role for methimazole in autoimmune thyroid disease: inducing T cell
      apoptosis.

PMID- 10958304
TI  - Fas ligand expression in thyroid follicular cells from patients with thionamide
      treated Graves' disease.
AB  - Thionamides are used in the treatment of Graves' disease (GD) and act mainly by
      inhibiting the organification of iodide, but also lower the levels of thyroid
      autoantibodies, sometimes leading to long-term remission. Fas ligand (FasL)
      induces apoptosis of susceptible cells by cross-linking its own receptor, Fas.
      While Fas is present in a wide variety of normal tissues, FasL expression is
      limited mainly to cells of the immune system, where it acts as an effector
      molecule of cell-mediated cytotoxicity, and to the placenta, brain, eye, and
      testis where it presumably contributes to their immune-privileged status by
      eliminating infiltrating lymphocytes. We examined immunohistochemically the
      presence of FasL in thyroid tissue from 15 glands of thionamide-treated GD
      patients and in 8 normal thyroid control specimens. We also investigated the
      presence of FasL in thionamide-treated thyrocytes in vitro and their ability to
      induce Fas-mediated apoptosis in lymphocytes. We found that FasL expression was
      very weak to undetectable in normal thyroid tissue and cultured thyrocytes,
      whereas it was strong in thionamide-treated GD glands and cultured thyrocytes.
      Methimazole-treated thyrocytes induced FasL-dependent apoptosis in cocultured
      lymphocytes, whereas methimazole treatment of lymphocytes grown in the absence of
      thyrocytes had no such effect. We conclude that FasL is highly expressed in
      follicular cells of thyroid glands obtained from thionamide-treated Graves'
      patients and may contribute to the immunomodulatory effect of thionamides in this
      disease.

PMID- 10958305
TI  - The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97
      murine thyrotropic tumors.
AB  - Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth.
      Somatostatin has been implicated as a synergistic factor in the inhibition of
      thyrotrope function. We have previously shown that pharmacological doses of
      thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic
      tumors in association with upregulation of somatostatin receptor type 5 (sst5)
      mRNA and somatostatin receptor binding. In the current study, we examined the
      effect of physiological thyroid hormone replacement alone or in combination with
      the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor
      growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as
      well as somatostatin receptor binding sites. Physiological LT4 replacement
      therapy resulted in tumor shrinkage in association with increased sst5 mRNA
      levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding.
      Sandostatin LAR alone had no effect on any parameter measured. However,
      Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA
      production and reduced final tumor weights to a greater degree. In this paradigm,
      Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These
      data suggest an important interaction between the somatostatinergic system and
      thyroid hormone in the regulation of thyrotrope cell structure and function.

PMID- 10958306
TI  - Recombinant human thyroid peroxidase produced in insect cells has similar
      properties to native human thyroid peroxidase.
AB  - Purified native human thyroid peroxidase (nTPO) isolated from thyroid tissue and
      recombinant (r)TPO produced in High Five insect cells have been compared. nTPO
      and rTPO were purified to about 95% homogeneity and showed similar UV and visual
      spectra and similar 412 nm per 280 nm absorbance ratios (0.4 for nTPO and 0.4 for
      rTPO). The nTPO and rTPO guaiacol oxidation enzyme activities were about 1,000
      guaiacol units per milligram of protein. TPO autoantibody binding characteristics
      of nTPO and rTPO were analyzed in an assay based on 125I-labeled nTPO and
      precipitation with protein A. In the assay, the effect of unlabeled nTPO or rTPO
      on TPO autoantibody binding from 25 patients sera was studied. Unlabeled nTPO or
      rTPO (from 0 to 160 ng/mL) inhibited the binding of TPO autoantibodies in a dose
      dependent manner in the case of each serum studied (from 100% in the absence of
      unlabeled TPO to 5%-10% in the presence of 160 ng/mL of TPO). The inhibition
      profile for each serum was essentially identical in the case of both TPO
      preparations. The effect of TPO autoantibodies on enzyme activity of rTPO was
      analyzed after incubation of rTPO with TPO autoantibody-positive serum
      immunoglobulin G (IgG) (n = 12), TPO monoclonal antibodies reactive with two
      different epitopes on the TPO, IgG (n = 3) from glutamic acid decarboxylase
      autoantibody positive patient sera, and IgG (n = 3) from healthy blood donors.
      Effective complexing of TPO by TPO autoantibodies was tested by precipitating the
      complexes with solid phase protein A and measuring the TPO enzyme activity in the
      resulting supernatants. These studies showed that the TPO enzyme activity was not
      affected by incubation with TPO autoantibody-positive IgG or monoclonal
      antibodies despite effective complexing of the autoantibodies with TPO. Overall,
      our studies demonstrate that nTPO and rTPO produced in insect cells are very
      similar in terms of enzyme activity, UV and visible spectra, and reactivity with
      autoantibodies. Furthermore, in our study, TPO autoantibodies did not appear to
      inhibit TPO enzyme activity.

PMID- 10958307
TI  - Binding of rat thyroglobulin to heparan sulfate proteoglycans.
AB  - We previously showed that rat thyroglobulin (Tg) is a heparin-binding protein and
      that heparin inhibits Tg binding to megalin (gp330), an endocytic Tg receptor
      found on the apical surface of thyrocytes. Cooperation between cell surface
      receptors and heparin-like molecules, namely heparan sulfate proteoglycans
      (HSPGs), can facilitate cell surface binding of some heparin-binding proteins.
      Based on our previous findings indicating that heparin and megalin-binding sites
      of rat Tg are functionally related, here we investigated whether rat Tg binds to
      HSPGs, which are expressed by thyroid cells. We showed in solid phase assays that
      unlabeled rat Tg binds to a heparan sulfate (HS) preparation in a dose-dependent,
      saturable manner, with moderately high affinity (Kd approximately 19 nM, Ki
      approximately 25 nM). Binding was inhibited by heparin and by HS itself. We then
      studied the role of HSPGs in Tg binding to FRTL-5 cells, a differentiated Fisher
      rat thyroid cell line. As previously reported, after incubation of FRTL-5 cells
      with unlabeled rat Tg at 4 degrees C, heparin released virtually all the cell
      bound Tg. Co-incubation of Tg with HS or with a preparation of HSPGs resulted in
      a reduction of binding by 35%-40%. When FRTL-5 cells were preincubated with
      heparitinase or heparinase I, which released 20%-30% of cell surface HSPGs, Tg
      binding was reduced to a similar extent. An antibody against a Tg heparin-binding
      site functionally related to a major megalin-binding site virtually abolished Tg
      binding to HS and to FRTL-5 cells, supporting the hypothesis that combined
      interactions of Tg with HSPGs and with megalin are involved in Tg binding to rat
      thyroid cells.

PMID- 10958308
TI  - Death of the autoimmune thyrocyte: is it pushed or does it jump?
AB  - Programmed cell death or apoptosis is central both in physiology during
      development and in disease. The mechanism of apoptosis is under the control of
      antiapoptotic survival genes of the Bcl-2 family and proapoptotic death receptors
      of the TNF superfamily (Fas, TNFR, TRAILR). Following death signal, the death
      receptor binds to its own receptor and initiates, through binding of adaptors, a
      cascade of events mediated by the autoproteolytic activation of specific enzymes
      called caspases. This enzyme activation is ultimately responsible for the
      dissembly of basic nuclear and cytoplasmic cell structures leading to cell death.
      In certain cell systems, antiapoptotic genes of the Bcl-2 family prevent the
      proapoptotic pathway. One of their roles is to maintain mitochondrial function
      integrity. In autoimmune destructive thyroiditis high levels of apoptosis have
      been demonstrated particularly within the destructed follicles near the
      infiltrated areas in comparison to Graves' disease and non autoimmune glands. In
      Hashimoto's thyroiditis Fas expression has been found increased on thyrocytes and
      in vitro can be modulated by proinflammatory cytokines. FasL expression on
      thyrocytes remains controversial. Thyroid cells from Graves' disease and
      multinodular glands are known to kill Fas expressing target cells although
      Hashimoto's thyrocytes are not efficient effector cells. Intrathyroidal
      lymphocytes from Hashimoto's thyroids maintain functional killer activity. These
      findings would suggest that intrathyroidal lymphocytes could be responsible for
      thyrocyte death in vivo. Whether this mechanism is Fas/FasL, TRAIL/TRAILR
      dependent can not be confirmed as specific blocking reagents were not able to
      inhibit cell induced death. In Hashimoto's thyroiditis an impairment of Bcl-2 and
      Bcl-X anitapoptotic genes on thyrocytes has also been detected. Bcl-X expression
      can be down-regulated in vitro by incubation with cytokines. These findings
      suggest that thyrocyte death may not exclusively be the result of specific
      interactions between death receptor and their ligands but it may involve
      simultaneous impairment of protective genes of the Bcl-2 family. Whether the
      impairment of the Bcl-2 family is a direct consequence of environmental stimuli
      or is the result of an intrinsic thyrocyte (mitochondrial?) alteration is as yet
      not known.

PMID- 10958309
TI  - Are posttherapy radioiodine scans informative and do they influence subsequent
      therapy of patients with differentiated thyroid cancer?
AB  - Posttherapy scans (PTS) with a gamma camera are typically used after therapeutic
      doses of 131I to visualize metastases that may not be seen with lower dose
      diagnostic scans. During a 16-month period, we studied 81 patients (64 with
      papillary thyroid cancer and 17 with follicular thyroid cancer), who had both a
      diagnostic whole-body scan (131I dose 3 mCi) and a PTS. A total of 117 PTS were
      evaluated. At the time of PTS, clinical or radiologic evidence of metastatic or
      residual disease was present in 68 patients (84%). The anatomic sites of known
      disease included, neck (63), mediastinum (23), lung (35), bone (14), trachea
      (16), esophagus (5), and brain (2). PTS showed focal areas of abnormal uptake not
      seen in diagnostic scans in 15 scans (13%). Areas with abnormal new uptake
      included: neck (5), lung (5), mediastinum (4), bone (2), and adrenal (1). In 7
      patients (9%) the PTS results impacted future decisions regarding plans for
      subsequent diagnostic scanning and 131I therapy or changed the patient's risk
      group category. IN CONCLUSION: (1) 13% of 117 PTS demonstrated abnormal foci of
      131I uptake not seen on pretherapy scans and (2) PTS changed management strategy
      in 9% of the studied patients.

PMID- 10958310
TI  - The prevalence and clinical significance of blocking thyrotropin receptor
      antibodies in untreated hyperthyroid Graves' disease.
AB  - The goal of this study was to evaluate the clinical significance of the blocking
      thyrotropin receptor antibodies (TSHRAb) in Graves' disease. The amount of
      blocking and stimulating TSHRAb were measured in 200 patients with untreated
      hyperthyroid Graves' disease using several cell lines carrying different TSHR
      chimera. Stimulating TSHRAb were measured in Chinese hamster ovary (CHO) cells
      with wild-type human TSHR (CHO-hTSHR) or a TSHR chimera with residues 90-165
      (Mc2) or 8-165 (Mc1+2) substituted by equivalent residues of rat luteinizing
      hormone/chorionic gonadotrophin (LH/CG) receptor or in FRTL-5 cells. Blocking
      TSHRAb were measured in Mc2 cells. The activities of different TSHRAb were
      assessed and clinical features were compared to patients who were positive or
      negative for blocking TSHRAb antibodies. Blocking TSHRAbs were detected in 18.5%
      of patients (37/200) with hyperthyroid Graves' disease. Patients with blocking
      antibodies had significantly lower mean stimulating TSHRAb activities than those
      without blocking antibodies in wild-type CHO-hTSHR cells (301 +/- 179 vs. 446% +/
      537%, p = 0.005). Mean stimulating TSHRAb activities measured by FRTL-5, Mc1+2,
      or Mc2 cells and mean thyrotropin receptor inhibitor immunoglobulin (TBII)
      activities were not different between the two groups. The patients with blocking
      antibodies were not different from those without blocking antibodies in age,
      gender ratio, initial serum free thyroxine (T4) levels, or goiter size. However,
      the prevalence of exophthalmos was higher (35.1% vs. 17.5%, p = 0.024) in the
      patients with blocking antibodies than those without. In summary, the presence of
      blocking TSHRAb is not rare in patients with hyperthyroid Graves' disease when
      measured with chimeric receptor expressing cells. Blocking TSHRAb in Graves' sera
      do not strongly antagonize the action of stimulating TSHRAb in vivo, but could be
      a major factor responsible for underestimation of stimulating TSHRAb activities
      measured by CHO-hTSHR. The association of blocking TSHRAb with ophthalmopathy
      suggests that the TSHRAb repertoire of Graves' patients is different in those who
      do and who do not have ophthalmopathy.

PMID- 10958311
TI  - Treatment of anaplastic thyroid carcinoma with paclitaxel: phase 2 trial using
      ninety-six-hour infusion. Collaborative Anaplastic Thyroid Cancer Health
      Intervention Trials (CATCHIT) Group.
AB  - Anaplastic thyroid carcinoma is a rare, lethal disease with no effective systemic
      therapies. Preclinical studies demonstrated antineoplastic activity of
      paclitaxel. This prompted a prospective phase 2 clinical trial to determine
      activity of paclitaxel against anaplastic thyroid carcinoma in patients with
      persistent or metastatic disease despite surgery or local radiation therapy.
      Twenty patients, entered through 6 of 12 study sites, were treated with 96-hour
      continuous infusion paclitaxel every 3 weeks for 1 to 6 cycles; the first 7
      patients received 120 mg/m2 per 96 hours and the rest received 140 mg/m2 per 96
      hours. Total responses to therapy were assessed using modified criteria with
      response durability acceptable at 2 or more weeks, due to the exceedingly rapid
      growth rate of this tumor. Plasma samples were obtained for pharmacokinetic
      analyses. Off-protocol, data showed that 9 patients were later treated with 225
      mg/m2 paclitaxel as weekly 1-hour infusions. Nineteen evaluable patients
      demonstrated a 53% total response rate (95% confidence interval, 29%-76%) with
      one complete response and nine partial responses (including one off protocol).
      Results of historical review off-protocol showed 2 of 7 patients, with prior
      partial responses to the 96-hour infusion, had subsequent partial responses to
      weekly treatment and 1 of 2 prior nonresponders gained a partial response to
      weekly therapy. No toxicities greater than grade 2 were seen with 96-hour
      infusions, while peripheral neuropathy (up to grade 3) was most common with
      postprotocol weekly infusions. Paclitaxel appears to be the only agent with
      significant clinical systemic activity against anaplastic thyroid carcinoma;
      however, it is not capable of altering the lethality of this malignancy,
      suggesting the need for additional therapeutic innovations. Decreased time
      intervals between paclitaxel infusions may be more efficacious.

PMID- 10958312
TI  - Treatment with propylthiouracil is associated with appearance of antineutrophil
      cytoplasmic antibodies in some patients with Graves' disease.
AB  - The use of propylthiouracil (PTU) for the treatment of Graves' disease is
      associated with few adverse effects such as skin eruptions, liver dysfunction,
      and agranulocytosis. Furthermore, recent studies described the development of
      antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and
      vasculitis in patients treated with PTU. Here we investigated whether PTU therapy
      per se is associated with the appearance of ANCA in patients with Graves'
      disease. We analyzed 119 serum samples from 117 patients with Graves' disease
      treated with either PTU (n = 56), or methimazole (MMI) (n = 21), as well as
      untreated patients (n = 42). Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)
      ANCA were tested by enzyme-linked immunosorbent assay (ELISA) kits. MPO-ANCA was
      negative in all patients treated with MMI therapy and untreated patients.
      However, MPO-ANCA was detected in 21 (37.5%) of 56 patients treated with PTU
      therapy. Furthermore, two patients who were negative for MPO-ANCA became positive
      after PTU therapy. The proportion of patients positive for MPO-ANCA increased
      with the prolongation of PTU therapy, but did not correlate with age, gender, and
      positive antithyroperoxidase (TPO) antibody. Among 21 MPO-ANCA positive patients,
      12 had no symptoms, but 9 patients complained of myalgia, arthralgia, or common
      cold like symptoms after the appearance of MPO-ANCA. Three patients developed
      agranulocytosis or granulocytopenia, but none showed abnormal urinary findings.
      Our results suggest that PTU per se is associated with the production of MPO-ANCA
      in patients with Graves' disease.

PMID- 10958313
TI  - Graves' disease and low-output cardiac dysfunction: implications for autoimmune
      disease in endomyocardial biopsy tissue from eleven patients.
AB  - Classic high-output thyrotoxic heart disease is generally considered a direct
      effect of thyroid hormone. In contrast, the cause of the less common low-output
      heart failure is generally unknown. The aim of this study was to retrospectively
      evaluate available endomyocardial biopsy tissue from patients with coexistent
      Graves' disease and idiopathic low-output heart failure and determine whether the
      biopsy features were consistent with an autoimmune process. The study group
      consisted of 11 patients whose mean age was 47 years when they were diagnosed
      with hyperthyroidism and 52 years when diagnosed with cardiac dysfunction. Right
      ventricular endomyocardial biopsy tissue revealed severe lymphocytic myocarditis
      in a patient with severe ophthalmopathy and showed borderline myocarditis in a
      patient without ophthalmopathy. Biopsy tissues from 6 other patients showed
      appreciable myocyte hypertrophy and interstitial fibrosis, consistent with
      dilated cardiomyopathy. Two patients had nondiagnostic biopsy specimens, and 1
      patient had features suggestive of arrhythmogenic right ventricular dysplasia. In
      conclusion, for the 11 patients with Graves' disease and unexplained systolic
      dysfunction, only 2 (18%) had lymphocytic infiltrates consistent with an
      autoimmune process. Thus, among patients with Graves' disease, most cases of low
      output cardiac dysfunction appear to be due to causes other than an active
      autoimmune inflammatory process.

PMID- 10958314
TI  - Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis.
AB  - Thyroid storm is a rare and life-threatening complication of untreated
      thyrotoxicosis. A number of neurological complications have been described in
      association with thyrotoxicosis. We report the case of a 28-year-old woman with a
      thyroid storm on the basis of Graves' disease and probably triggered by a
      surgical procedure. She developed cerebral venous thrombosis (CVT) of the left
      transverse and rectus sinus with a venous infarction of the left thalamus. Except
      for an increased factor VIII clotting activity there were no thrombophilic
      abnormalities. Similar cases have been described in the literature and the
      reported incidence of the combination of CVT and thyrotoxicosis is significantly
      higher than expected by chance alone (0.1 x 10(-6) per year vs. 0.0032 x 10(
      6)/year). This case is consistent with the assumption that thyrotoxicosis,
      probably through a factor VIII-mediated hypercoagulability, may be a predisposing
      factor for the development of CVT.

PMID- 10958315
TI  - Thyrotoxicosis in a male patient associated with excess human chorionic
      gonadotropin production by germ cell tumor.
AB  - We report a case of a man with thyrotoxicosis due to excess production of human
      chorionic gonadotropin (hCG) by metastatic choriocarcinoma, followed by
      alterations of his thyroid function tests by nonthyroidal illness. All reported
      cases of thyrotoxicosis due to high hCG levels in male patients are reviewed.
      Patients with this syndrome usually have widespread choriocarcinoma and
      relatively few symptoms of thyrotoxicosis. Typically, if the patient survives the
      metastatic germ cell tumor, the thyrotoxicosis resolves as the hCG levels
      decrease after chemotherapy directed at the choriocarcinoma. Only rarely are
      specific antithyroid medications required. The hCG molecule directly stimulates
      the thyroid gland, and these patients appear to have in the serum a predominance
      of acidic variants of hCG with greater intrinsic thyroid-stimulating activity
      than the hCG secreted during a normal pregnancy. In general, these patients have
      a poor prognosis due to the usually widespread nature of the germ cell tumor at
      the time of diagnosis.

PMID- 10958316
TI  - Images in thyroidology. Embolization of a bone metastasis of follicular thyroid
      carcinoma.

PMID- 10958317
TI  - Lack of antigenicity of recombinant human thyrotropin after multiple injections
      in patients with differentiated thyroid cancer.

PMID- 10958318
TI  - FTIR spectroscopic and HPLC chromatographic studies of carbon tetrachloride
      induced acute hepatitis in rats: damage in liver phospholipid membrane.
AB  - Carbon tetrachloride (CCl4) induced rat hepatitis was studied by observing an
      FTIR spectrum of the liver microsomal or homogenate extract compared with those
      of model compounds. The microsomal extract from the liver of healthy control rats
      showed almost the same spectrum as a mixture of phosphatidylcholine and
      phosphatidylethanolamine (2:1 by weight). Intraperitoneal injection of CCl4
      decreased the absorption intensity due to th --C--H in the--C==H at 3012 cm(-1)
      in the microsomal extract, and it developed a new 1,2-diacylglycerol band at 1070
      cm(-1) in the homogenate extract. An HPLC study was added to assign the 1070 cm(
      1) band to 1,2-diacylglycerol. These findings were interpreted from the
      peroxidation of the microsomal membrane and the regenerative proliferation of the
      damaged cell.

PMID- 10958319
TI  - Raman and surface-enhanced Raman scattering spectroscopy of bis-netropsins and
      their DNA complexes.
AB  - The interactions of three bis-netropsins (bis-Nts), which are potent catalytic
      inhibitors of DNA-binding enzymes, with three double-stranded oligonucleotides
      (OLIGs), which contain sites of different specific affinities for each bis-Nt,
      were analyzed. Raman spectroscopy was performed for selective monitoring of
      modifications of the bis-Nt or the OLIG structure upon bis-Nt-DNA binding, and
      surface-enhanced Raman scattering spectroscopy (SERS) was an additional tool for
      topology studies of ligand-DNA complexes. The spectral data showed conformational
      changes of both partners (bis-Nt and OLIG) upon complexation. Structural
      variations of bis-Nts appeared to be dependent on a bis-Nt-OLIG binding constant
      and were found to be small in the specific DNA binding and highest for
      nonspecific binding of bis-Nt with the corresponding OLIG. The conformational
      changes of the OLIGs were varied with a bis-Nt-OLIG binding constant in the same
      manner. The bis-Nts seemed to induce a perturbation in the OLIG's structure, as
      well as in the positions of their direct binding. These DNA structural
      modification effects may explain the inhibition of DNA-binding enzymes in the
      variety of very distinct DNA-enzyme binding sites by bis-Nts reported previously.

PMID- 10958320
TI  - Infrared spectroscopy of human cells and tissue. VIII. Strategies for analysis of
      infrared tissue mapping data and applications to liver tissue.
AB  - Experimental and computational methods of infrared microspectroscopy (IRI-MSP)
      and infrared spectral mapping (ISM) are presented. These methods are subsequently
      applied to the analysis of cirrhotic liver tissue. The sensitivity of infrared
      spectral mapping toward spectral changes caused by disease will be demonstrated.
      In addition, the excellent agreement between ISM data and histopathological
      information will be discussed.

PMID- 10958322
TI  - Donor fluorescence decay analysis for energy transfer in double-helical DNA with
      various acceptor concentrations.
AB  - We studied fluorescence resonance energy transfer between donors and acceptors
      bound to double-helical DNA. The donor Hoechst 33258 binds to the minor groove of
      DNA and the acceptor propidium iodide (PI) is an intercalator. The time-resolved
      donor decays were measured in the frequency domain. The donor decays were
      consistent with a random 1-dimensional distribution of acceptors. The decays were
      analyzed in terms of three 1-dimensional models: a random continuous acceptor
      distribution; acceptors placed on discrete lattice sites; and a cylindrical model
      with the acceptor in the center, and the donors on a cylinder surface. The data
      were well described by all three models. Interpretation in terms of continuous
      distribution of acceptors revealed a minimum donor to acceptor distance of 13 A,
      which is 3 bp from the center of Hoechst 33252. These results suggest that PI is
      excluded from the 4 bp covered by Hoechst 33252 when it is bound to the minor
      groove of DNA.

PMID- 10958321
TI  - Heme symmetry, vibronic structure, and dynamics in heme proteins: ferrous
      nicotinate horse myoglobin and soybean leghemoglobin.
AB  - We report the visible and Soret absorption bands, down to cryogenic temperatures,
      of the ferrous nicotinate adducts of native and deuteroheme reconstituted horse
      heart myoglobin in comparison with soybean leghemoglobin-a. The band profile in
      the visible region is analyzed in terms of vibronic coupling of the heme normal
      modes to the electronic transition in the framework of the Herzberg-Teller
      approximation. This theoretical approach makes use of the crude Born-Oppenheimer
      states and therefore neglects the mixing between electronic and vibrational
      coordinates; however, it takes into account the vibronic nature of the visible
      absorption bands and allows an estimate of the vibronic side bands for both
      Condon and non-Condon vibrational modes. In this framework, an x-y splitting of
      the Q transition for native and deuteroheme reconstituted horse myoglobin is
      clearly assessed and attributed to electronic perturbations that, in turn, are
      caused by a reduction of the typical D(4h) symmetry of the system due to heme
      distortions of B(1g)-type symmetry and/or to an x-y asymmetric position of the
      nicotinate ring; in deuteroheme reconstituted horse myoglobin the asymmetric heme
      peripheral substituents add to the above effect(s). On the contrary, in
      leghemoglobin-a no spectral splitting upon nicotinate binding is observed,
      pointing to a planar heme configuration in which only distortions of A(1g)-type
      symmetry are effective and to which the nicotinate ring is bound in an x - y
      symmetric position. The local dynamic properties of the heme pocket of the three
      proteins are investigated through the temperature dependence of spectral line
      broadening. Leghemoglobin-a behaves as a softer matrix with respect to horse
      myoglobin, thus validating the hypothesis of a looser heme pocket conformation in
      the former protein, which allows a nondistorted heme configuration and a
      symmetric binding of the bulky nicotinate ligand.

PMID- 10958324
TI  - The pill and cancer.
AB  - The relation between oral contraceptives (OC) and cancer risk has been
      investigated extensively, mainly with reference to breast, female genital tract,
      liver cancer and cutaneous malignant melanoma, and will be summarized below.
      There is also some suggestion that OC use is related to other neoplasms,
      including a reduced risk of colorectal cancer among OC users, but the issue is
      still controversial and too preliminary to provide indications for informed
      contraception choice.

PMID- 10958323
TI  - Redox-linked conformational changes in bovine heart cytochrome c oxidase:
      picosecond time-resolved fluorescence studies of cyanide complex.
AB  - Picosecond time-resolved fluorescence studies are carried out on cyanide
      inhibited and heat-modified cytochrome c oxidase in aqueous lauryl maltoside
      surfactant solution, as well as in an aqueous vesicle, to understand the
      conformational changes associated with electron transfer and proton pumping
      activity of the enzyme. The tryptophan fluorescence decay profiles follow a four
      exponential model, which also matches the lifetime maxima obtained in a maximum
      entropy method analysis. The fast lifetime components are highly affected by the
      reduction and chemical modification of the enzyme. Changes in these lifetime
      components are related to the conformational changes in the vicinity of the heme
      centers of the enzyme. The cyanide-inhibited enzyme in the oxidized form shows a
      fluorescence decay profile similar to that of the native oxidized form,
      indicating that the conformational changes due to cyanide binding are very small.
      However, reduction of the cyanide-inhibited enzyme that leaves cyanide bound heme
      alpha3 oxidized causes a large increase in the fluorescence lifetimes, which
      indicates very significant conformational changes due to electron transfer to the
      dinuclear Cu(A) and heme alpha centers. A comparison of the tryptophan
      fluorescence decay of various other modified forms of the enzyme leads us to
      propose that the possible site of conformational coupling is located near heme
      alpha instead of the binuclear heme alpha3-Cu(B) center.

PMID- 10958325
TI  - Breast cancer--can risks really be lessened?
AB  - Breast cancer, although uncommon in western populations in the past, continues to
      rise in incidence, and now affects up to one woman in nine. In some countries,
      such as the US and Australia, the mortality rate is decreasing, albeit slightly.
      In developing populations, while of low occurrence, the disease is rising in
      incidence. Risk factors, which include certain reproductive practices, diet and
      physical activity, while apparent in some contexts, appear much less so in
      others; moreover, the avoiding measures do not lend themselves to primary
      prevention. For early detection, although regular mammography is advocated, it is
      a subject of controversy. Basically, avoiding measures fall within the usual
      recommendations for a 'prudent' lifestyle - avoid obesity, increase physical
      activity, stop smoking and restrict alcohol consumption.

PMID- 10958326
TI  - Energetic factors, ovarian steroids and the risk of breast cancer.
AB  - In industrial countries, women often have excess metabolic energy due to high
      food consumption and low physical activity. High lifetime energy availability
      results in high lifetime levels of ovarian steroid hormones. Oestrogens and
      progesterone are hypothesized to play a crucial role in the development and
      prognosis of breast cancer. Epidemiological studies document the importance of
      physical activity and caloric limitations in reducing breast cancer risk. The
      risk of breast cancer is much higher in industrial countries than in developing
      countries, where women are characterized by lower energy intake and higher energy
      expenditure. It is likely, that the beneficial effects of physical activity and
      of negative energy balance are mediated by the reduced levels of ovarian
      steroids. While both weight loss and physical activity may have similar efficacy
      in suppressing ovarian function and, therefore, in reducing the risk of breast
      cancer, we suggest that it may be more advantageous for premenstrual women to
      achieve lifetime reduction in steroid levels by increasing their physical
      activity, rather than by weight loss due to caloric restriction alone.

PMID- 10958327
TI  - Coffee and cancer: a review of epidemiological studies, 1990-1999.
AB  - Epidemiological studies on the relation between coffee consumption and cancer
      risk have been mainly focused on cancers of the urinary bladder, pancreas and
      colorectum. The relation between coffee and bladder cancer is controversial,
      despite a large number of studies published over the last three decades. In most
      studies, the risk tends to be higher in coffee drinkers than in those who do not
      drink coffee, but the excess risk is generally moderate and is neither dose- nor
      duration-related. Thus, a strong association between coffee drinking and bladder
      cancer can be excluded, although it is still unclear whether the weak association
      is causal or nonspecific and due to some bias or confounding. For pancreatic
      cancer, a possible association with coffee consumption has been postulated in a
      large case-control study published in 1981; since then, however, most studies
      have shown no substantial association, and overall evidence suggests that coffee
      is not materially related to pancreatic cancer risk. Overall evidence on the
      coffee-colorectal cancer relation suggests an inverse association, since most
      case-control studies found odds ratios below unity, particularly for colon
      cancer. The pattern of risk is less clear for cohort studies. A plausible
      biological explanation has been given in terms of coffee-related reduction of
      bile acids and neutral sterol secretion in the colon. For other cancer sites,
      including oral cavity, oesophagus, stomach, liver, breast, ovary, kidney and
      lymphoid neoplasms, the relation of coffee drinking with cancer risk has been
      less extensively investigated, but the evidence is largely reassuring.

PMID- 10958328
TI  - Food groups and oesophageal cancer risk in Vaud, Switzerland.
AB  - The influence of food groups on oesophageal cancer risk was analysed using data
      from a case-control study conducted between 1992 and 1999 in the Swiss Canton of
      Vaud on 101 incident, histologically confirmed cases (92 squamous cell, 9
      adenocarcinomas) and 327 controls admitted to hospital for acute, non-neoplastic
      conditions. Multivariate odds ratios (OR) were computed after allowance for age,
      sex, tobacco, alcohol and non-alcohol energy. Significant increased risks emerged
      for red meat (OR = 1.7 for an increase of one serving per day), pork and
      processed meat (OR = 1.6), and eggs (OR = 1.5), whereas inverse associations were
      observed for milk (OR = 0.7), raw and cooked vegetables (OR = 0.5), citrus and
      other fruits (OR = 0.5), as well as for a more varied diet (OR = 0.5). Most
      associations were apparently stronger in heavy alcohol drinkers, suggesting an
      interaction between poor diet and alcohol drinking in oesophageal carcinogenesis.

PMID- 10958329
TI  - Different expression of some molecular markers in sporadic cancer of the left and
      right colon.
AB  - The expression of cytoplasmic c-erbB2, epidermal growth factor receptor (EGFR),
      proliferating cell nuclear antigen (PCNA) and dipeptidylpeptidase IV (DPP IV) was
      significantly higher in sporadic cancer of the right than of the left colon. In
      addition, cytoplasmic c-erbB2 displayed the same difference in the adjacent (less
      than 2 cm) and distant (more than 5 cm from the tumour margin) mucosa. The
      findings cannot be related to Dukes staging. It is suggested that different
      ontogenic development of the right (from the midgut) and the left (from the
      hindgut) colon may be a possible explanation. Therefore, data on the expression
      of different molecular markers in colorectal cancer and surrounding mucosa should
      always be supplemented by data on tumour location.

PMID- 10958330
TI  - Probability of early repeat Pap smear in an integrated cervical screening
      programme.
AB  - The integration of routine Pap smear practice based on self-referral into an
      organized programme based on personal invitation is the recommended approach to
      cervical cancer screening. In this study, the cytology archive of the integrated
      cervical screening programme implemented in the Faenza district (northern Italy)
      was used to compare the population of women responding to invitation with that of
      self-referred women for the cumulative probability of early (< 36 months) repeat
      Pap smear after a negative result. Between 1995 and 1998, women aged 25-64 living
      in five municipalities of the district were targeted by the first round of the
      programme. Eligible for the study were 2356 women responding to invitation for
      screening and 2221 women not invited because of self-referral for Pap smear at
      any other setting. The probability of early repeat Pap smear was estimated by the
      life table method. Differences were evaluated by the Gehan test. Multivariate
      determinants were assessed by the Cox regression analysis. At 36 months' follow
      up, the cumulative probability of early repeat Pap smear was 44% among self
      referred women and 6% among women responding to invitation (relative hazard =
      4.8). For self-referred women, the probability was related to age (with a peak at
      35-44 years), previous Pap smear history and municipality of residence. Among
      women responding to invitation, only an inverse association with age was
      demonstrated. In conclusion, the observed differences in overall probability and
      determinants of early repeat Pap smear between the two screening populations
      provided important information on Pap smear usage in the total target population.

PMID- 10958331
TI  - Salivary excretion of N-nitrosodimethylamine in dogs.
AB  - Carcinogenic N-nitroso compounds (NOCs) are not only ingested from the
      environment but are also formed endogenously from precursors. It has been
      reported that nitrate, an NOC precursor, has an enterosalivary cycle and that the
      cycle increases the chance of exposure to NOCs. However, there is no information
      on the salivary excretion of NOCs. In the present study, the toxicokinetics of N
      nitrosodimethylamine (NDMA) in dogs was evaluated, focusing on the salivary
      excretion. Following intravenous injection of 2 mg/kg NDMA, the plasma
      concentration showed a monoexponential decline, and the total body clearance and
      apparent distribution volume were greatly in excess of the hepatic plasma flow
      and total body water, respectively. A high concentration of NDMA was immediately
      detected in the plasma after oral administration of the same dose, and the oral
      bioavailability was almost 100%. NDMA was rapidly excreted into the saliva after
      both treatments, and the concentration in saliva was higher than that in the
      plasma. These results suggest that NDMA also has an enterosalivary cycle: NDMA is
      partially excreted from blood into saliva, delivered into the gastrointestinal
      tract by swallowing the saliva, and then completely reabsorbed into the systemic
      circulation. This concept was also supported by kinetic analysis based on a
      compartment model. The enterosalivary cycle of NDMA cannot be ignored in the risk
      assessment of carcinogenesis.

PMID- 10958332
TI  - Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous
      extract of Momordica charantia.
AB  - The anticarcinogenic effect of aqueous extract of fruit of Momordica charantia
      (bitter gourd), which is widely used as a vegetable in India, was studied in a
      two-step skin carcinogenesis model in mice. The possible mode of action was also
      investigated. Oral administration of the fruit extract was found to have an
      adverse effect on the general health and lifespan of the animals when used at a
      high concentration. But when this dose was reduced by half, the test extract
      afforded protection from the development of skin tumour and increased life
      expectancy. Carcinogen-induced lipid peroxidation in liver and DNA damage in
      lymphocytes were found to be reduced following treatment with Momordica. The
      fruit extract was found to significantly activate the liver enzymes glutathione-S
      transferase, glutathione peroxidase and catalase (P < 0.001), which showed a
      depression following exposure to the carcinogen. The results suggest a preventive
      role of water-soluble constituents of M. charantia fruit during carcinogenesis,
      which is mediated possibly by their modulatory effect on enzymes of the
      biotransformation and detoxification system of the host.

PMID- 10958333
TI  - But I am not so think as you drunk I am.

PMID- 10958334
TI  - Glycoprotein-associated amino acid exchangers: broadening the range of transport
      specificity.
AB  - Members of the newly discovered glycoprotein-associated amino acid transporter
      family (gpaAT-family) share a similar primary structure with >40% identity, a
      predicted 12-transmembrane segment topology and the requirement for association
      with a glycoprotein (heavy chain) for functional surface expression. Five of the
      six identified gpaATs (light chains) associate with the surface antigen 4F2 heavy
      chain (4F2hc = CD98), a ubiquitous plasma membrane protein induced in cell
      proliferation, and which is also highly expressed at the basolateral surface of
      amino acid transporting epithelia. The differing tissue localizations of the
      4F2hc-associated gpaATs appear to complement each other. As yet, a single gpaAT
      (b(0,+)AT) has been shown to associate with rBAT, a 4F2hc-related glycoprotein
      mainly localized in intestine and kidney luminal brush-border membranes. The
      transport characteristics of gpaATs have been shown, by expression in
      heterologous systems, to correspond to the previously described transport systems
      L, y+L, xc- and b(o,+). These (obligatory) exchangers of broad substrate
      specificity (with the exception of xCT) are expected to equilibrate the
      concentrations of their substrate amino acids across membranes. Thus, the driving
      force provided by a transmembrane gradient of one substrate amino acid, such as
      that generated by a parallel functioning unidirectional transporter, can be used
      by a gpaAT to fuel the secondary active vectorial transport of other exchangeable
      species. Vectorial transport of specific amino acids is also promoted by the
      intrinsic asymmetry of these exchangers. The fact that genetic defects of the
      epithelial gpaATs b(0,+)AT and y+LAT1 cause non-type I cystinuria and lysinuric
      protein intolerance, respectively, demonstrates that these gpaATs perform
      vectorial secondary and/or tertiary active transport of specific amino acids in
      vivo.

PMID- 10958335
TI  - Phsyiological relevance of aquaporins: luxury or necessity?
AB  - Aquaporins are members of a large family of pore-forming intrinsic membrane
      proteins, the MIP family. Based on their permeability properties they are now
      further subdivided into aquaporins, with real water-selective pores, and
      aquaglyceroporins with slightly less selective pores. Aquaporins are expressed in
      a large variety of tissues throughout the body but in most situations it is not
      clear whether their presence is necessary for the proper physiological function
      of these tissues. This review focuses on recent insight into the physiological
      relevance of aquaporins gained from studying aquaporin knockout mouse models and
      from diseases, on new surprising findings related to gating and selectivity, and
      on the consequences of tetramerization for routing and the genetics of
      nephrogenic diabetes insipidus. The active fluid transport in proximal tubules
      and in salivary glands is seriously compromised by aquaporin deletion. This is in
      contrast to lung, airways and stomach, where active fluid transport proceeds
      unhindered in the face of greatly reduced water permeabilities due to aquaporin
      deletion. Therefore, aquaporins seem to be a necessity at extreme high rates of
      active fluid transport but appear to be more of a luxury at medium or low fluid
      transport rates.

PMID- 10958336
TI  - Nephritogenic ochratoxin A interferes with mitochondrial function and pH
      homeostasis in immortalized human kidney epithelial cells.
AB  - The ubiquitous nephritogenic and carcinogenic fungal metabolite ochratoxin A
      (OTA) has been shown to interact with renal cell function at low nanomolar
      concentrations. This is possibly brought about through changes in cellular pH
      (pHc) homeostasis and mitochondrial function. We assessed the effect of nanomolar
      concentrations of OTA on pHc homeostasis and the possible involvement of
      mitochondria using immortalized human kidney epithelial (IHKE1) cells. Within
      seconds OTA evoked a decrease of pHc with a threshold concentration of 0.1
      nmol/l, followed by a sustained alkalinization. Acidification was the same in
      bicarbonate and non-bicarbonate Ringer solution. When Ca2+ entry across the
      plasma membrane was prevented, virtually no OTA-induced pH changes could be
      observed. Inhibition of Na+/H+-exchange (NHE, Na+-free solution) and H+-ATPase
      (bafilomycin A1) did not reduce the OTA-induced acidification. By contrast,
      determination of NHE activity as a function of pHc revealed that OTA stimulates
      NHE (maximal flux increases) in a Ca2+-dependent manner. OTA exposure did not
      increase lactic acid production, indicating that anaerobic glycolysis was not
      enhanced. Inhibiting complexes I, III and IV of the mitochondrial electron
      transport chain (ETC) with rotenone, antimycin A and CN- prevented the OTA
      induced acidification almost completely. Completely inhibiting F1FO-ATPsynthase
      with oligomycin reduced the effect of OTA by approximately equal 50%. In
      addition, OTA induced a hyperpolarization of the mitochondrial membrane potential
      (psim) in a Ca2+-dependent manner. Furthermore, OTA exposure resulted in a
      mitochondria-dependent increase of the cellular ATP content. We conclude that OTA
      activates mitochondria and NHE by interfering with cellular Ca2+ homeostasis.
      Stimulation of mitochondrial metabolism leads to enhanced "proton production".
      Anaerobic glycolysis is not enhanced.

PMID- 10958337
TI  - ATP-sensitive potassium channels in freshly dissociated adult rat striatal
      neurons: activation by metabolic inhibitors and the dopaminergic receptor agonist
      quinpirole.
AB  - The characteristics of adenosine 5'-triphosphate (ATP)-sensitive K+ channels in
      acutely isolated striatal neurons from adult rats were examined. Neurons had a
      resting membrane potential of -53.9+/-1.2 mV (n=66), with evoked or spontaneous
      action potentials firing at 10+/-0.7 Hz, and large inwards and outwards whole
      cell currents. In cell-attached patches with a high [K+] in the pipette, a
      voltage-independent, ATP-insensitive 16.5+/-1.5 pS channel was observed in 375
      out of 452 cells. Bath application of Na+-azide (0.5-2 mM) to 108 neurons
      revealed another 145.7+/-3.5 pS (LKATP) channel in 65 neurons; this channel was
      blocked by tolbutamide. The LKATP channel exhibited a high open probability (Po,
      0.8+/-0.05) at 0 mV pipette potential. Varying the pipette [K+] shifted the
      reversal potential of LKATP, showing the channel's K+ selectivity. Cytoplasmic
      ATP (ATPi) reversibly inhibited LKATP, with an inhibitory constant (Ki) of 0.12
      mM. LKATP was sensitive to intracellular Ca2+ but insensitive to iberiotoxin. In
      25% of cell-attached patches, the presence of quinpirole in the pipette opened a
      third type of channel (90.6+/-1.7 pS, termed D2KATP). Sulpiride, a dopamine D2
      receptor antagonist, inhibited D2KATP. ATPi reversibly inhibited D2KATP, with a
      Ki of 0.212 mM. The Na+-azide- or quinpirole-induced current caused a tolbutamide
      sensitive membrane hyperpolarization and a marked reduction in action potential
      frequency. We propose that ATP-sensitive K+ channels play a metabolism-dependent
      role in striatal neurons.

PMID- 10958338
TI  - Effect of neuropeptide Y on the sympathetic contraction of the rabbit central ear
      artery during cooling.
AB  - In order to analyse the effect of neuropeptide Y (NPY) on the cutaneous vascular
      response to sympathetic nerve stimulation during cooling, the isometric response
      of isolated 2-mm segments of the rabbit central ear (cutaneous) artery was
      recorded at 37 degrees C and during cooling (30 degrees C). Electrical field
      stimulation (4-16 Hz) at 37 degrees C produced a frequency-dependent contraction,
      which was reduced during cooling (45% for 16 Hz) and potentiated by NPY (10(-8),
      3x10(-8) and 10(-7) M), this potentiation being greater at 30 degrees C than at
      37 degrees C. The NPY-induced potentiation of the contraction elicited by
      electrical field stimulation (8 Hz) was abolished by an antagonist of Y1 subtype
      NPY receptors, BIBP3226 (10(-6) M), at 37 degrees C and 30 degrees C, reduced by
      phentolamine (10(-6) M) at 30 degrees C but not at 37 degrees C, was not modified
      by the purinoceptor antagonist PPADS (3x10(-5) M) and was reduced by application
      of both phentolamine and PPADS at both temperatures. Both NiCl2 (10(-3) M) and
      verapamil (10(-5) M) abolished the potentiating effect of NPY at 37 degrees C and
      reduced it at 30 degrees C. Neither application of an inhibitor of nitric oxide
      synthesis, L-Nomega-nitro-arginine (L-NOARG, 10(-4) M), nor endothelium removal
      modified the potentiating effect of NPY at 37 degrees C or 30 degrees C. NPY (10(
      8), 3x10(-8) and 10(-7) M) potentiated in a concentration-dependent way the
      arterial contraction in response to exogenous noradrenaline (10(-8)-10(-4) M) at
      30 degrees C but not at 37 degrees C, and it increased the response to ATP (10(
      4)-10(-2) M) at both temperatures. Therefore, in cutaneous (ear) arteries: (1)
      NPY potentiates the sympathetic response at 37 degrees C and at 30 degrees C, (2)
      this potentiating effect of NPY was more marked at 30 degrees C than at 37
      degrees C, probably because of greater potentiation of the alpha-adrenoceptor
      response during cooling, and (3) the potentiating effect of NPY at both
      temperatures is mediated by NPY receptors of the Y1 subtype, is dependent of Ca2+
      channels and is independent of the release of endothelial nitric oxide.

PMID- 10958339
TI  - Cyclic nucleotide-gated channels: intra- and extracellular accessibility to Cd2+
      of substituted cysteine residues within the P-loop.
AB  - In cyclic nucleotide-gated (CNG) channels from the bovine rod, the pore loop "P
      loop", connecting the S5 and S6 transmembrane segments, is formed by the residues
      R345-S371 (here named R1-S27). It determines channel selectivity and contributes
      to gating. We have studied its topology, by testing the accessibility to Cd2+ of
      serially substituted cysteine residues. Channels were expressed in Xenopus
      oocytes. The accessibility of V4C, S6C, T16C, 117C, T20C, P22C and S27C from the
      cytoplasmic side of the plasma membrane was tested by applying 1-100 microM Cd2+
      to the inner face of inside-out patches, at negative membrane potentials. Under
      these conditions, the effect of Cd2+ on wild-type channels was negligible. The
      accessibility of the same residues from the external side of the membrane was
      tested by measuring CNG current inhibition persisting after wash-out of Cd2+
      applied to outside-out patches. T16C and I17C channels were strongly inhibited by
      Cd2+ from the inside, in the presence of cGMP. The Kd for T16C block was 16
      microM. Thus the T16 and I17 residues participate directly in channel function
      and are accessible from the cytoplasmic side when the channels are open. In
      contrast, V4C, T20C and P22C residues were only inhibited when 100 microM Cd2+
      was applied externally, suggesting that V4C, T20C and P22C face the outer side of
      the P-loop.

PMID- 10958340
TI  - cAMP-independent decrease of ATP-sensitive K+ channel activity by GLP-1 in rat
      pancreatic beta-cells.
AB  - Using the patch-clamp method, we studied the mechanism of depolarization of rat
      pancreatic beta-cells induced by glucagon-like peptide 1 (7-36) amide (GLP-1).
      GLP-1 caused depolarization in a concentration-dependent manner (0.2-100 nM).
      Exendin (9-39) amide, a GLP-1 receptor antagonist, prevented the GLP-1-induced
      depolarization. GLP-1 reduced tolbutamide-sensitive membrane currents evoked by
      voltage ramps from -90 to -50 mV, recorded in the perforated whole-cell
      configuration, suggesting that GLP-1 decreased the activity of the ATP-sensitive
      K+ channel (KATP). This GLP-1 effect was prevented by exendin (9-39) amide. In
      cells treated with Rp-cAMPS, an inhibitor of the cAMP-dependent protein kinase
      (PKA), GLP-1 still caused depolarization and reduced the whole-cell membrane
      current through KATP. Examined in the cell-attached configuration, 20 nM GLP-1,
      applied out of the patch, had little effect on KATP activity. In the inside-out
      configuration, the open time probability and the single-channel conductance of
      KATP in the absence of ATP inside the membrane were unaffected by the presence of
      20 nM GLP-1 in the pipette. In both conditions, application of ATP to the inside
      of the membrane reduced KATP activity. The half-maximal concentrations (ki) of
      ATP were 11.6 microM without and 5.6 microM with 20 nM GLP-1 in the pipette
      (P<0.05). The values of the Hill coefficient (h) were 1.03 without and 1.01 with
      GLP-1. We conclude that GLP-1 reduces KATP activity by elevating the sensitivity
      of KATP to ATP, resulting in depolarization of pancreatic beta-cells. This GLP-1
      action is independent of the cAMP signalling pathway.

PMID- 10958342
TI  - Comparison of the activation of the Ca2+ release-activated Ca2+ current ICRAC to
      InsP3 in Jurkat T-lymphocytes, pulmonary artery endothelia and RBL-1 cells.
AB  - In many electrically non-excitable cells, Ca2+ entry is mediated predominantly by
      the store-operated Ca2+ influx pathway. The best-characterised store-operated
      Ca2+ current is the Ca2+ release-activated Ca2+ current (ICRAC). It is generally
      believed that high concentrations of intracellular Ca2+ buffer are required to
      measure ICRAC, due to Ca2+-dependent inactivation of the channels. Recently, we
      have recorded robust ICRAC in rat basophilic leukaemia (RBL-1) cells at
      physiological levels of Ca2+ buffering when stores were depleted by inhibition of
      the sarcoplasmic/ endoplasmic reticulum Ca2+-activated adenosine triphosphatase
      (SERCA) pumps. However, the second messenger inositol 1,4,5-trisphosphate (InsP3)
      was not able to evoke the current under such conditions, despite inducing
      substantial Ca2+ release. We have therefore suggested that a threshold exists
      within the Ca2+ stores which has to be overcome for macroscopic ICRAC to
      activate. To establish whether this is a specific feature of ICRAC in RBL-1 cells
      or whether it is a more general phenomenon, we investigated whether a threshold
      is also seen in other cell-types used to study store-operated Ca2+ entry. In
      Jurkat-T lymphocytes, ICRAC is activated weakly by InsP3 in the presence of low
      concentrations of Ca2+ buffer, whereas the current is large when SERCA pumps are
      blocked simultaneously, as in RBL-1 cells. Although the electrophysiological
      properties of ICRAC in the Jurkat cell are very similar to those of RBL-1 cells,
      the Na+ conductance in the absence of external divalent cations is quite
      different. Unexpectedly, we failed consistently to record any store-operated Ca2+
      current in macrovascular pulmonary artery endothelia whereas robust ICRAC was
      seen under the same conditions in RBL-1 cells. Our results show that ICRAC has a
      similar profile of activation in the presence of physiological levels of Ca2+
      buffering for Jurkat T-lymphocytes and RBL-1 cells, indicating that the threshold
      mechanism may be a general feature of ICRAC activation. Because ICRAC in
      pulmonary artery endothelia is, at best, very small, additional Ca2+ influx
      pathways may also contribute to agonist-induced Ca2+ entry.

PMID- 10958341
TI  - Tamoxifen inhibits Ca2+ uptake by the cardiac sarcoplasmic reticulum.
AB  - Ca2+ transients in isolated cardiac ventricular myocytes and the amount of Ca2+
      that could be released from the sarcoplasmic reticulum (SR) in these cells by
      caffeine were reduced in the presence of tamoxifen. To examine the effects of
      tamoxifen on the cardiac muscle SR directly, isolated SR vesicles and fluorimetry
      methods were used to measure the uptake of Ca2+ by the SR and the ATPase activity
      of the SR Ca2+ pump. SR Ca2+ uptake was inhibited by tamoxifen at concentrations
      greater than 2.4 microM. Half-maximal inhibition was seen at approximately 5
      microM. Inhibition of uptake was not due to the development of a substantial
      tamoxifen-dependent leak of Ca2+ from the SR or to a direct inhibitory effect of
      tamoxifen on the ATPase activity of the SR Ca2+ pump. In addition to its effect
      on SR Ca2+ uptake, tamoxifen also reduced the rate at which stored Ca2+ could be
      released from the SR by the Ca2+ ionophore 4-bromo A23187. Our results are
      consistent with the hypothesis that tamoxifen inhibits an ion current that
      accompanies Ca2+ movement across the SR membrane. This possibility is also
      consistent with the known inhibitory action of tamoxifen on some types of Cl- and
      K+ channels.

PMID- 10958343
TI  - Ryanodine- and thapsigargin-insensitive Ca2+-induced Ca2+ release is primed by
      lowering external Ca2+ in rabbit autonomic neurons.
AB  - Rises in cytosolic Ca2+ induced by a high K+ concentration (30 or 60 mM) (K+
      induced Ca2+ transient) were recorded by fluorimetry of Ca2+ indicators in
      cultured rabbit otic ganglion cells. When external Ca2+ ([Ca2+]o) was reduced to
      a micromolar (10-40 microM) or nanomolar (<10 nM) level prior to high-K+
      treatment, K+-induced Ca2+ transients of considerable amplitude (50% of control)
      were generated in most cells, although those initiated at normal [Ca2+]o were
      reduced markedly or abolished by reducing [Ca2+]o during exposure to a high K+
      concentration. Lowering [Ca2+]o alone occasionally caused a transient rise in
      cytosolic Ca2+. K+-induced Ca2+ transients at micromolar [Ca2+]o were repeatedly
      generated and propagated inwardly at a speed slower than that at normal [Ca2+]o,
      while those at nanomolar [Ca2+]o occurred only once. K+-induced Ca2+ transients
      at micromolar [Ca2+]o were not blocked by ryanodine (10 microM), carbonyl cyanide
      p-(trifluoromethoxy) phenylhydrazone (FCCP, 5 microM: at 20-22 degrees C but
      blocked at 31-34 degrees C) or thapsigargin (1-2 microM), but were blocked by
      Ni2+ (1 mM) or nicardipine (10 microM). Thus, there is a ryanodine-insensitive
      Ca2+-release mechanism in FCCP- and thapsigargin-insensitive Ca2+ stores in
      rabbit otic ganglion cells, which is primed by lowering [Ca2+]o and then
      activated by depolarization-induced Ca2+ entry. This Ca2+-induced Ca2+ release
      may operate when [Ca2+]o is decreased by intense neuronal activity.

PMID- 10958344
TI  - Measurement of calcium entry and exit in quiescent rat ventricular myocytes.
AB  - The aim of this work was to obtain the first quantitative measurements of Ca2+
      influx and efflux in quiescent cardiac cells. The relationship between free and
      total Ca2+ was obtained during a caffeine application. This buffering curve was
      then used to calculate changes of total Ca2+ from measurements of free cytosolic
      [Ca2+] ([Ca2+]i) made with Indo-1. The rate of Ca2+ removal from the cytoplasm
      was calculated by differentiating total Ca2+ with respect to time. The dependence
      of d(total Ca2+)/dt on [Ca2+]i was hyperbolic. Inhibition of either Na+-Ca2+
      exchange (by addition of 10 mmol l(-1) NiCl2 or removal of external Na+) or the
      sarcolemmal Ca2+-activated adenosine triphosphatase (Ca2+-ATPase) (with
      carboxyeosin) decreased the calculated efflux. In both cases, the main effect was
      on the apparent maximum rate (Vmax) with little effect on the Michaelis-Menten
      constant (Km). These results suggest that the Na+-Ca2+ exchange and Ca2+-ATPase
      have very similar affinities for [Ca2+]i and that their fractional contributions
      do not change over the systolic range of [Ca2+]i. Ca2+ influx was quantified in
      two ways. The first method was to extrapolate the curve relating Ca2+ efflux to
      [Ca2+]i to zero [Ca2+]i. This gave a value of 4.49+/-0.54 micromol l(-1) s(-1)
      which was reduced to zero by either removal of external Ca2+ or addition of Ni2+.
      In other experiments external Ca2+ was removed and the maximum rate of fall of
      total Ca2+ calculated as 2.53+/-0.93 micromol l(-1) s(-1). This approach can be
      used to provide a quantitative analysis of the control of resting [Ca2+]i.

PMID- 10958345
TI  - Effects of medium hypertonicity on water permeability in the mammalian rectum:
      ultrastructural and molecular correlates.
AB  - Minute-by-minute net water fluxes (Jw) were measured across the isolated rectal
      epithelium in rats and rabbits. Five minutes after a serosal (but not mucosal)
      hypertonic challenge (plus 200 mosmol/l) a significant increase in the basal Jw
      was recorded in both species [deltaJw, microl min(-1) cm(-2): 0.40+/-0.06 (rats);
      0.45+/-0.10 (rabbits)]. At the same time, most epithelial cells shrank markedly
      while the intercellular spaces were wide open (electron microscopy studies). In
      freeze-fracture studies multi-strand tight-junction structures (only slightly
      modified by serosal hypertonicity in rabbits) were observed in control
      conditions. No structural changes were observed after mucosal hypertonicity (both
      in rats and rabbits). Immunohistochemical studies showed the expression of
      aquaporin 3 (AQP3) at the basolateral membrane of epithelial cells in the rat. A
      first conclusion is that the epithelium of the mammalian rectum is a highly
      polarized, aquaporin-3-containing, water permeability structure. The Jw increase
      induced by serosal hypertonicity was sensitive to mercurial agents in both
      species and no changes in unidirectional [14C]mannitol fluxes (Ps) or
      transepithelial resistance (RT) were observed during this Jw increase. These
      observations suggest a transcellular route for the osmotically induced increase
      in water fluxes. In the rabbit rectum the initial Jw response, associated with
      serosal hypertonicity, was a transient one. It was followed by a second, slow and
      HgCl2-sensitive Jw increase (a transient peak in paracellular mannitol
      permeability was also observed). A second conclusion is that serosal
      hypertonicity induces an increase in transcellular water permeability in both rat
      and rabbit rectum.

PMID- 10958346
TI  - Influence of ammonia on sodium absorption in rat proximal colon.
AB  - The influence of ammonia on sodium and chloride fluxes in rat proximal colon was
      studied in Ussing chamber experiments. Under short-circuit conditions, the
      proximal colon absorbed sodium and secreted chloride. The presence of ammonia (30
      mmol 1(-1) mucosal) diminished Na+ absorption, but had hardly any influence on Cl
      fluxes. Blocking the apical Na+/H+ exchanger isoform NHE2 by amiloride or HOE642
      diminished absorptive Na+ and Cl- fluxes. In contrast, the NHE3-specific
      antagonist S3226 was ineffective. Amiloride and HOE642 also inhibited the effect
      of ammonia on net sodium absorption. In bicarbonate-free buffer solution, ammonia
      failed to alter the absorptive fluxes of sodium and chloride, but increased the
      secretory fluxes of Na+ and Cl-. The latter effect was blocked by HOE642. These
      results suggest that basal NaCl absorption in rat proximal colon depends to a
      large extent on NHE2. Mucosal ammonium decreases Na+ absorption and this effect
      can be antagonized by blocking NHE2. This observation suggests that ammonium
      interacts with the apical Na+/H+ exchanger, thereby diminishing sodium
      absorption.

PMID- 10958347
TI  - Imaging plasma membrane proteins in large membrane patches of Xenopus oocytes.
AB  - We describe the preparation of a Xenopus oocyte plasma membrane patch attached to
      a cover-slip with its intracellular face exposed to the bath solution. The
      proteins attached to the plasma membrane were visualized by confocal microscopy
      after fluorescence labelling. Since cortical microfilament elements were detected
      in these plasma membrane preparations we termed the patches plasma membrane
      cortex patches. The way these patches are formed and the low concentration of
      proteins needed for cytochemical detection make the membrane-cortex patches
      similar to electrophysiological membrane patches and therefore allow the
      cytochemical study of ion channels to be correlated with electrophysiological
      experiments. Furthermore, the described patch is similar to manually isolated
      plasma membranes used for biochemical analysis by sodium dodecylsulphate
      polyacrylamide gel electrophoresis (SDS-PAGE). Cytochemical analysis of membrane
      cortex patches also enables the detection of the two-dimensional pattern of
      organization of membrane proteins (clustered or non-clustered forms). In
      addition, patch preparations enable cytochemical study of the relative
      localization of membrane proteins. The methodology enables integration of
      electrophysiological, biochemical and cytochemical studies of ion channels,
      giving a comprehensive perspective on ion channel function.

PMID- 10958348
TI  - The functional state of the isolated rabbit kidney perfused with autologous
      blood.
AB  - This report describes the technique and procedure for perfusing an isolated
      rabbit kidney with 25 ml heparinized autologous blood in a closed circuit
      including a pump and an oxygenator. The duration of the operative ischaemia was 5
      8 min; the perfusion lasted 2.5 hours. An additional infusion was made to
      compensate for urinary losses. Renal blood flow increased progressively from
      2.01+/-0.1 to 2.65+/-0.22* ml/g kidney weight (kw) per min (*P<0.05). Between the
      first (P1) and the last (P4) urine collection period the glomerular filtration
      rate (GFR) fell from 288+/-25 to 217+/-38* microl/g kw per min, urine flow from
      5.58+/-1.13 to 4.91+/-0.75 microl/g kw per min, Na+ excretion from 1.07+/-0.19 to
      0.63+/-0.12* micromol/g kw per min, K+ excretion from 0.46+/-0.03 to 0.28+/-0.05*
      micromol/g kw per min, P excretion from 2.5+/-0.2 to 2.0+/-0.5 microg/g kw per
      min, Ca excretion from 0.4+/-0.1 to 0.12+/-0.05* microg/g kw per min, creatinine
      excretion from 6.94+/-0.32 to 5.68+/-0.54 microg/g kw per min, glucose excretion
      from 18.2+/-3.2 to 1.6+/-0.5* microg/g kw per min, the free water clearance
      (CH2O) from -6.57+/-0.85 to -5.10+/-1.31 microl/g kw per min and urine osmolality
      from 600+/-52 to 590+/-105 mOsm/kg, urea excretion from 0.75+/-0.16 to 0.95+/
      0.13 micromol/g kw per min. Excretion of glucose, P or Ca was observed only above
      a given plasma threshold value, and no transport maximum was found for glucose or
      P. Ca reabsorption paralleled the Na reabsorption. The proximal tubule pressure,
      measured within the 1st h of perfusion, was 12.5+/-1.1 mm Hg. Histological
      examination at the end of the perfusion showed dilatation of the tubules as in
      the non-perfused kidneys, and the presence of numerous bacteria. Hypertonic urine
      (380-1110 mOsm/kg) was observed in the presence of vasopressin, in the latter's
      absence the urine was hypotonic urine (206-278 mOsm/kg). There was no correlation
      between renal plasma flow and the GFR. CH2O increased with increasing filtered
      Na+ load. In conclusion, the blood-perfused, isolated rabbit kidney has a fairly
      constant functional capacity for approximately 2 h.

PMID- 10958349
TI  - A simple method for obtaining functionally and morphologically intact primary
      cultures of the medullary thick ascending limb of Henle's loop (MTAL) from rabbit
      kidneys.
AB  - We describe a simple method for obtaining functionally and morphologically intact
      primary cultures of cells from the medullary thick ascending limb of rabbit
      kidneys. After digesting dissected fragments of the inner stripe of the outer
      medulla with collagenase, a suspension of tubule fragments is obtained, the vast
      majority of which are medullary thick ascending limb (MTAL) segments. These are
      identified individually by their morphological appearance and large amounts are
      collected with a micropipette mounted on a micromanipulator. This ensures maximal
      homogeneity of the starting material. Monolayers of cells grow out of these MTAL
      segments after seeding them onto collagen-coated, permeable filter supports.
      During the week following confluence, the cultures exhibit an apical side
      positive transepithelial potential difference. Electron microscopic examination
      shows a monolayer of polarised cells with characteristics of distal tubular
      cells. The primary cultures express Tamm-Horsfall protein at their apical
      surface. Additional evidence for their differentiation and polarisation is the
      net ammonium influx, which occurs at very high rates across the apical membrane
      and is much slower across the basolateral membrane, as judged by measurements of
      intracellular pH. Adenosine 3',5'-cyclic monophosphate (cAMP) production is
      stimulated by arginine-vasopressin, calcitonin or isoproterenol (all 1
      micromol/l). Intracellular calcium signalling is observed after stimulation with
      1 micromol/l adenosine, adenosine 5'-triphosphate (ATP) and bradykinin. In
      addition, we compared these characteristics with those of TALH-SVE cell
      monolayers, an established immortalised cell line of the same origin.

PMID- 10958350
TI  - Bypassing hybridoma technology: HLA-C reactive human single-chain antibody
      fragments (scFv) derived from a synthetic phage display library (HuCAL) and their
      potential to discriminate HLA class I specificities.
AB  - The generation of discriminative, monospecific anti-HLA antibodies used to be a
      difficult endeavor. Phage display technology, using single-chain antibody
      fragments (scFv) offers a powerful alternative obtaining target-specific,
      genetically stable reagents. Most of scFv obtained to date have been enriched by
      panning phage libraries to solid-phase coupled antigens. In the present study,
      HLA-C-specific scFv were isolated using a synthetic phage library in combination
      with a Cw*0602 overexpressing cell line. ScFv from this procedure precipitated
      HLA-Cw*0602 heavy chains from whole cell lysates. Flow cytometry analysis
      revealed that scFv stained HLA-Cw*0602-positive cells, but not cells expressing
      HLA alleles Cw*0302, Cw*0802, A*0201, B*2705, or Gm1*01011, indicating the
      specificity of scFv. Similarly they showed an ability to discriminate Cw*0602
      positive from Cw*0602-negative peripheral blood lymphocytes (PBL). The results of
      our study demonstrate the feasibility to genetically engineer single-chain HLA
      class I-specific antibodies, by phage display technology. This approach might be
      a valuable tool to develop a broad range of novel monospecific antibodies against
      HLA-class I specificities.

PMID- 10958351
TI  - Definition of peptide binding motifs amongst the HLA-A*30 allelic group.
AB  - HLA class I molecules present endogenously processed peptide ligands for
      surveillance by the T-cell receptor. This potentially immunogenic surface of HLA
      and peptide is a consequence of the polymorphism found within the HLA molecule
      and its preference for ligand binding together with peptide conformation within
      the binding groove. To investigate the relation between the polymorphic
      differences between some closely related HLA alleles and their effect on peptide
      preference, transfectants were established, each containing one of four allelic
      variants of HLA-A*30. Peptides from all four transfectants were eluted, and both
      individual ligands and peptide pools were sequenced. The data shows two distinct
      peptide motifs which distinguish A*3001 from the other three known A*30 variants.
      Differences in preferences at minor positions within the peptide sequence were
      noted between A*3002, A*3003 and A*3004, providing additional evidence of the
      implications of sequence polymorphism to HLA function.

PMID- 10958352
TI  - Identification of tumor antigen-specific cytotoxic T lymphocytes cross
      recognizing allogeneic major histocompatibility class I molecules.
AB  - Adoptive immunotherapy of cancer utilizes tumor antigen-specific cytotoxic T
      lymphocytes (CTL) as mediators of a targeted anti-tumor effect. In this study, we
      show that such CTL can be able to cross-recognize allogeneic major
      histocompatibility complex (MHC) molecules in a phenomenon of molecular mimicry.
      A self histo-leukocyte antigen (HLA) A*0201-restricted CTL specific for peptide
      MT27-35 from the human differentiation antigen Melan-A/MART-1 was shown to cross
      recognize allogeneic A*0220 molecules which differ from syngeneic A*0201 for a
      single amino acid substitution at position 66 of the antigen-binding groove.
      A*0220 molecules were recognized on a variety of human cells of different
      histological origin but not on COS-7 cells. A second self-A*0201-restricted CTL,
      specific for peptide D10/6-271 encoded by the tumor-specific DAM-gene family, was
      shown to cross-recognize allogeneic B*3701 molecules which differ from syngeneic
      A*0201 by 32 amino acids in the peptide antigen-binding cleft. B*3701 molecules
      were recognized on a variety of cell types including COS-7 cells. These data
      raise new safety issues for clinical trials of cancer immunotherapy using
      adoptive transfer of in vitro generated, allogeneic CTL with specific anti-tumor
      activity.

PMID- 10958353
TI  - Melanomas and melanoma cell lines do not express HLA-G, and the expression cannot
      be induced by gammaIFN treatment.
AB  - HLA-G is an effective ligand of natural killer (NK) inhibitory receptors, HLA-G
      transcripts have been detected in several human tumors, and cytokines like gamma
      interferon (IFN) enable HLA-G molecules to be expressed. These findings are
      particularly upsetting in case of melanomas: IFN treatment is frequently included
      in melanoma therapeutic protocols, and downregulation of classical class I
      molecules occurs in nearly half of these tumors. Therefore, a melanoma cell
      downregulating classical class I and de novo expressing HLA-G, either
      constitutively or upon IFN treatment, is probably a stealthy target for the
      immune system, having inhibited both the cytotoxic T lymphocyte (CTL) and the NK
      activity. To elucidate this point we have investigated the expression of HLA-G
      molecules in 45 melanoma cell lines before and after gammaIFN treatment. Analysis
      was performed by immunofluorescence and flow cytometry, using the anti-HLA-G
      MoAbs 87G and G233, by Western blot, using the anti-HLA-G MEM/G1 MoAb and PAG1
      antiserum, and by RT-PCR analysis. In addition, 8 melanoma tissues from patients
      free from therapy and 6 nevi were studied by immunohistochemistry using the 87G
      MoAb. No evidence was gathered of HLA-G expression, neither constitutive nor, in
      cell lines, after gammaIFN treatment. We therefore conclude that HLA-G expression
      is an uncommon event in melanomas, and that a therapy including IFNs cannot harm
      the patient by inducing the de novo expression of HLA-G molecules at least in its
      G1 isoform.

PMID- 10958354
TI  - A novel variant of the MHC-linked hsp70, hsp70-hom, is associated with rheumatoid
      arthritis.
AB  - The three major histocompatibility complex (MHC)-linked hsp70s have been screened
      for variation in their 28 kDa C-terminal regions by direct nucleotide sequencing
      of the corresponding DNA fragments. No amino acid variation was detected in the
      major heat-inducible hsp70 (encoded by hsp70-1 and hsp70-2), although previously
      unreported silent mutations were identified in all three of the MHC-linked hsp70
      genes. A novel coding polymorphism, a G to A transition, was identified at
      nucleotide 2763 of hsp70-hom (hom-2763). This dimorphism results in a glutamic
      acid to lysine alteration at position 602 in the C-terminal domain of hsp70-hom.
      The frequencies of the A-2763 and G-2763 alleles were calculated to be 27% and
      73%, respectively. The hom-2763 dimorphism was characterised in 81 HLA-homozygous
      cell lines using an ARMS-PCR assay and A-2763 was found to be in strong linkage
      disequilibrium with DRB1*04 (Pc=1.31 x 10(-7), following Bonferoni's correction).
      Analysis of 60 rheumatoid arthritis (RA) families, each with an affected sib
      pair, revealed an association between hsp70-hom A-2763 and RA using both the
      transmission disequilibrium test (TDT) and the transmission to sib-pair (Tsp)
      test (P=0.0038 and P=0.013, respectively). This association may be due to linkage
      disequilibrium with HLA-DR alleles, but could represent an additional risk factor
      for RA in the MHC class III region.

PMID- 10958355
TI  - Major histocompatibility complex (MHC)-linked microsatellite markers in a founder
      population.
AB  - The Finnish population is genetically relatively homogeneous and has a narrow
      gene pool as a result of founder effect followed by rapid population growth. We
      here demonstrate that microsatellite markers are highly informative tools for
      major histocompatibility complex (MHC) analysis in this population. First, no
      variation in 12 MHC-linked microsatellites could be observed in certain CYP21
      deficient chromosomes, which as a result of founder effect most likely derived
      from common ancestors. Second, amongst 131 Finnish chromosomes, some, but not
      all, apparently HLA-identical chromosomes also carried identical microsatellites,
      suggesting that these loci could be applied for identification of haplotypes
      which have a relatively recent shared origins. Finally, when the microsatellites
      were studied between ethnically more distant individuals (Finnish vs. non
      Finnish), who were matched for the HLA alleles, much more differences were
      observed. This showed that the similarity in microsatellites was population
      specific. The microsatellite typing can therefore be informative in fine mapping
      MHC-linked susceptibility genes and can help in matching bone marrow transplants
      in isolated populations. Linkage disequilibrium was found to be much higher in
      the MHC than in another region (5q31) of similar size, indicating that there may
      be particular mechanisms keeping the MHC haplotypes conserved.

PMID- 10958356
TI  - HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac
      sarcoidosis.
AB  - Cardiac sarcoidosis occurs in 1-5% of sarcoidosis patients. We previously
      reported a significant increase of the uncommon TNFA (tumor necrosis factor
      alpha) allele, TNFA2 with cardiac sarcoidosis in Japanese. In order to precisely
      localize the susceptible locus for cardiac sarcoidosis within the HLA region,
      genetic polymorphisms of classical HLA genes, non-classical HLA class II genes
      such as HLA-DMA and -DMB genes and several genes involved in the class I-mediated
      antigen presentation pathway (TAP1, TAP2, LMP2 and LMP7) were investigated.
      Further, association analyses using four polymorphic microsatellite markers
      located around the TAP1 and TNFA genes were also carried out. As a result, HLA
      DQB1*0601 was found to be the most significantly associated allele, being more
      significantly increased than TNFA2. No significant increase of the DR52
      associated DRB1 alleles (DRB1*03, 05, 06 and 08), which was suggested to be
      primarily associated with lung sarcoidosis, was observed in cardiac sarcoidosis.
      A primary role of DQB1*0601 in determination of the susceptibility to cardiac
      sarcoidosis was supported by association analysis using four polymorphic
      microsatellite markers, in which only the TAP1 microsatellite locus, the nearest
      marker to the DQB1 gene among the microsatellites tested, displayed a significant
      positive association with cardiac sarcoidosis. On the other hand, the HLA
      DQB1*0501-DQA1*0101-DRB1*0101-B7 haplotype showed a negative association with the
      disease, as similarly observed in lung sarcoidosis. Thus, molecular mechanism for
      controlling the development of the disease related to HLA molecules are different
      between cardiac and lung sarcoidosis, whereas those for conferring a resistant
      trait may be similar to each other.

PMID- 10958357
TI  - Allelic diversity of Mhc-DRB alleles in rhesus macaques.
AB  - The Biomedical Primate Research Centre (BPRC) rhesus macaque colony was started
      with a large number of wild-caught animals originating mainly from the Indian
      subcontinent. The contemporary self-sustaining colony comprises approximately 800
      individuals. We screened a large section of the colony for Mamu-DRB polymorphisms
      by applying the denaturing gradient gel electrophoresis (DGGE) technique. Based
      on disparate DGGE profiles, animals were selected for nucleotide sequence
      analysis. This approach allowed the detection of 25 unreported Mamu-DRB alleles,
      bringing to 126 the total number of alleles documented in the literature. This
      communication demonstrates that rhesus macaques, like humans, display extensive
      allelic polymorphism at the DRB region. Phylogenetic analyses illustrate that
      humans and rhesus macaques share several Mhc-DRB loci and lineages. Identical
      exon 2 sequences, however, which are shared between humans and rhesus macaques,
      were not observed. This indicates that most primate Mhc-DRB alleles are of post
      speciation origin.

PMID- 10958358
TI  - Genomic typing of minor histocompatibility antigen HA-1 by reference strand
      mediated conformation analysis (RSCA).
AB  - Disparities in minor histocompatibility antigen (mHAg) HA-1 are involved in the
      development of acute graft-versus-host disease (GvHD) in adult recipient after
      HLA-identical sibling donor hematopoietic stem cell transplantation. The mHAg HA
      1 is an HLA-A*0201-restricted nonapeptide, which derives from the cleavage of a
      protein encoded at chromosome 19. The sequence analysis of HA-1 cDNA identified
      two alleles, termed HA-1H and HA-1R, which differ in only two nucleotides at 3'
      end of exon A, at positions 500 and 504. DNA-based methods for HA-1 typing were
      developed in 1998, using polymerase chain reaction with sequence-specific primers
      (PCR-SSP) and restriction fragment length polymorphism (PCR-RFLP). Here, we
      report the usefulness of reference strand mediated conformation analysis (RSCA),
      which was developed for mutation detection and typing of polymorphic loci, to
      discriminate between the two HA-1 alleles. We performed genomic typing of HA-1
      locus in 203 HLA-A*0201-positive samples using RSCA and we confirmed these
      results by PCR-SSP. The results demonstrate the high reproducibility of this
      method and their strong correlation with the results obtained by PCR-SSP (99%).
      Only two samples showed disparity between the RSCA typing and the PCR-SSP. Direct
      sequencing of these samples confirmed that the correct allele assignment was that
      obtained by the RSCA typing. Furthermore, HA-1- RSCA-based typing provides
      additional information about the intronic structure of both alleles. With this
      approach, we describe the almost constant presence (99.2%) of a 5-bp deletion at
      intronic position 214-218 associated to the HA-1H allele, previously
      unidentified. We conclude that HA-1 genomic typing by RSCA is easy to perform and
      that could be used as a routine typing method.

PMID- 10958359
TI  - A MAGE-A1 peptide presented to cytolytic T lymphocytes by both HLA-B35 and HLA-A1
      molecules.
AB  - Antigens encoded by melanoma antigen (MAGE) genes are of particular interest for
      cancer immunotherapy because of their strict tumoral specificity and because they
      are shared by many tumors. Antigenic peptide EADPTGHSY encoded by MAGE-A1 and
      known to be presented by HLA-A1 is currently being used in therapeutic
      vaccination trials. We report here that a cytotoxic T-lymphocyte (CTL) clone,
      which is restricted by HLA-B35, recognizes the same peptide and, importantly,
      lyses HLA-B35 tumor cells expressing MAGE-A1. This peptide can be presented to
      CTL by both HLA-B*3501 and HLA-B*3503 molecules, which are expressed by
      approximately 19% of Caucasians. These results infer that the current clinical
      use of peptide EADPTGHSY can now be extended to HLA-B35 patients.

PMID- 10958361
TI  - Identification of two new alleles HLA-DRB1*0312, DRB1*0432 and of a DRB3-negative
      DRB1*1313-positive haplotype.
AB  - Two new HLA-DRB1 alleles were identified in the course of routine class II
      molecular typing in Dutch Caucasoid. HLA-DRB1*0312 is similar to *03011 except
      for codon 57 (GAT-->AGC). DRB1*0432 is similar to *0413 but with a mutation at
      position 215, changing codon 72 (CGG-->CAG; Arg-->Gln). This sequence has never
      before been identified at this position. A DRB3-negative DRB1*1313 haplotype was
      identified in an individual from Indonesia. Monoclonal antibodies against DR52
      were nonreactive with lymphocytes of this individual. The DRB1*1313-DRB3-negative
      haplotype probably represents a recombination of DRB1*13 and *08 haplotypes where
      the sequences telomeric of HV1 are derived from the DRB3-negative DRB1*0803
      haplotype.

PMID- 10958360
TI  - Reference strand mediated conformation analysis resolves HLA-DRB1 typing
      ambiguities when matching for unrelated bone marrow transplantation.
AB  - We show here the use of reference strand mediated conformation analysis (RSCA) to
      unambiguously resolve the HLA-DRB1 typing of two individuals which were selected
      as potential unrelated donors for bone marrow transplantation (BMT). In the first
      case, both sequence-specific primer (SSP) amplification and sequence-specific
      oligonucleotide probing (SSO), routinely used in different tissue typing
      laboratories gave, for the two unrelated donors, the same ambiguous typing of HLA
      DRB1*04011+*0403 or DRB1*0407+*0413. In this case sequence-based typing (SBT) was
      not the method of choice to resolve the situation, due to the sequence
      ambiguities of these two given combinations. RSCA of both samples, using
      homozygous typing cells (HTCs) for DRB1*04011, *0403 and *0407 as internal
      controls, gave the unambiguous result that both donors were HLA-DRB1*04011+*0403.
      In the second case, a donor was typed as DRB1*1102+1103 by SSP, while SSO
      excluded the DRB1*1102 allele. The patient was unambiguously typed as
      DRB1*1101+1103 by both techniques. RSCA, using DNA from reference cell lines as
      internal controls, gave the unambiguous typing that the donor was DRB1*1103
      homozygous.

PMID- 10958363
TI  - The nucleotide sequence of two new DP alleles, DPA1*02015 and DPB1*8401,
      identified in a Chinese subject.
AB  - The HLA-DP genes (HLA-DPA1 and -DPB1) are encoded by the major histocompatibility
      complex (MHC) on human chromosome 6. They are involved in the presentation of
      antigen to CD4+ T cells as part of the class II antigen-presentation pathway.
      During a small study of Oriental subjects (11 Chinese and 26 Japanese subjects),
      one Chinese subject was identified as having numerous heterozygous sites within
      the second exon of both DPA1 and DPB1. These were further analysed using novel
      codon-specific primers. Sequencing analysis using these primers determined the
      subject to have DPA1*0103/*02015 and DPB1*0501/*8401; these new alleles have been
      submitted to GenBank and assigned the accession numbers AF098794 and AF077015,
      respectively.

PMID- 10958362
TI  - Identification of a new DRB3*02 allelic variant (DRB3*0209) by high-resolution
      sequence-based typing.
AB  - The HLA-DRB3/B4/B5 sequence-based typing method developed in this study in
      combination with PCR-SSP, enabled us to identify a new DRB3*02 allele, that was
      named as DRB3*0209 (GenBank accession number AF148518). This name has been
      officially assigned by the WHO Nomenclature Committee in May 1999. The new allele
      differs from DRB3*0207 by one substitution in codon 51 from AGG to ACG and
      another in codon 60 from TAC to TCC, resulting in aminoacid changes from Arg-
      >Thr (codon 51) and from Tyr-->Ser (codon 60). The DRB3*0209 allele was
      discovered in two related North Italian families. The fact that it was present in
      an hemizygous situation in three members of the paternal family and in one member
      of the secondary related family enabled us to isolate and sequence the new DRB3
      allele without cloning, to identify its association with the DRB1 locus, and to
      generate an Epstein-Barr virus (EBV)-transformed cell line, now present in our
      ECBR (European Collection for Biomedical Research) Cell Line Bank.

PMID- 10958364
TI  - Going back to the roots: effective utilisation of HLA typing information for bone
      marrow registries requires full knowledge of the DNA sequences of the
      oligonucleotide reagents used in the testing.
AB  - Information obtained by DNA-based HLA typing assays is more detailed and of
      higher quality than that obtained by conventional serological techniques.
      Nevertheless, it is common for data acquired in this way to be presented in the
      more familiar serological format. In many cases this representation can lead to
      significant loss of information, which may only become apparent at a later time,
      with the discovery of novel allele sequences. DNA-based typing methods, such as
      sequence-specific oligonucleotide probing (SSOP) or sequence-specific priming
      (SSP) generate fragmentary sequence data which is information rich. An
      alternative to assigning allele names to these fragments is to simply store the
      sequence data itself without interpretation. Bone marrow donor repositories can
      then be searched directly with sequence information, which though complex is more
      complete, rather than searching by derivative allele names.

PMID- 10958365
TI  - Nomenclature for factors of the HLA system, update March 2000. WHO Nomenclature
      Committee for Factors of the HLA System.

PMID- 10958366
TI  - Maximal accumulated oxygen deficit expressed relative to the active muscle mass
      for cycling in untrained male and female subjects.
AB  - The purpose of the present study was to determine if gender differences exist in
      the maximal accumulated oxygen deficit (MAOD) or in the blood lactate (Lac-) and
      catecholamine responses to the MAOD test (120% peak oxygen uptake to exhaustion).
      The MAOD for cycling was measured in ten untrained male and ten untrained female
      subjects using the method described by Medbo et al. (Anaerobic capacity
      determined by maximal accumulated oxygen deficit. J Appl Physiol 64: 50-60,
      1988). Blood Lac- and catecholamine concentrations were measured at rest,
      exhaustion and for 30 min following the MAOD test. Dual-energy X-ray
      absorptiometry was used to measure lean body mass (LBM) and to estimate the
      active muscle mass (AMM) for cycling. Males achieved a significantly higher MAOD
      than females following correction for AMM [126.3 (5.6) versus 108.3 (6.1) ml x kg
      AMM(-1), P = 0.04]. The peak blood lactate concentration ([Lac-]) in males [13.6
      (0.9) mmol x l(-1)] was significantly higher than in females [10.0 (1.0) mmol x
      l(-1)]. Males obtained a 68% higher peak epinephrine concentration ([Epi]) than
      females, but the difference was not significant [1268 (188) pg x ml(-1) versus
      755 (179) pg x ml(-1), P = 0.066]. However, plasma [Epi] was significantly higher
      for males than females at 1 min [824 (116) versus 489 (116) pg x ml(-1), P =
      0.036] and 3 min [330 (52) versus 179 (42) pg x ml(-1), P = 0.039] into the
      recovery period. No gender-dependent differences in the norepinephrine
      concentration were observed at any time. Peak [Lac-] was significantly correlated
      with MAOD (ml x kg AMM(-1)) in females (r = 0.75), but not in males (r = 0.09).
      The peak plasma [Epi] was not significantly correlated with MAOD (ml x kg AMM(
      1)) or peak [Lac-] in either group. These findings suggest that there are gender
      dependent differences in MAOD even when expressed relative to the AMM for
      cycling. The higher blood [Lac-] in males compared to females obtained after
      supramaximal exercise was not caused by enhanced secretion of Epi. The greater
      MAOD in untrained males was not caused by a greater ability to produce Lac- or by
      enhanced secretion of Epi.

PMID- 10958367
TI  - The measurement of plasma catecholamine and lactate thresholds: a comparison of
      methods.
AB  - Plasma lactate and catecholamine thresholds were calculated using three different
      variations of linear regression, an algorithmic linear regression method, a log
      log transformation method and a semi-log method. A group of 18 male sports
      science students undertook an incremental test to exhaustion on a cycle
      ergometer. A 5-ml blood sample was drawn at rest, after 4 min of exercise and
      every 2 min thereafter until the cessation of the test. Lactate, adrenaline and
      noradrenaline concentrations were measured. Lactate threshold (Th1a), adrenaline
      threshold (ThA) and noradrenaline threshold (ThNA) were calculated using each of
      the three methods. The best fits of the methods were examined by comparing their
      standard error of estimates (SEEs). The algorithmic method demonstrated a higher
      SEE than the other two methods, but only for Th1a and ThNA. The power output for
      which each method calculated the thresholds demonstrated a main effect for
      method. Tukey post hoc tests showed that the algorithmic method produced
      significantly higher outputs than the other two methods, which did not differ
      significantly from one another. Comparison of these power outputs showed that
      Th1a and ThA differed significantly, regardless of method, there were no other
      significant differences. Plasma concentrations of lactate, adrenaline and
      noradrenaline showed that the values of Th1a and ThNA calculated by the
      algorithmic method were significantly higher than those calculated using the
      other two methods, which did not differ significantly from one another. The only
      significant difference for ThA was between the algorithmic and semi-log methods.
      Correlations between the power outputs at which each method calculated the
      thresholds varied greatly between methods, and were at best only moderate (r =
      0.63). It was concluded that the algorithmic method was less powerful than the
      other two methods, and that Th1a, ThA and ThNA are not highly correlated.

PMID- 10958368
TI  - Effects of resistance exercise training on mass, strength, and turnover of bone
      in growing rats.
AB  - To determine the effects of resistance exercise on mass, strength and local
      turnover of bone, 50 Sprague Dawley rats, 8 weeks of age, were assigned to five
      groups: a baseline control and two groups of sedentary and exercising rats. The
      trunk of the rats was kept upright during electrically stimulated jumping
      exercise for 1 h every other day. In 4 weeks, the trabecular mineralizing surface
      per bone surface (MS/BS), bone formation rate per bone surface (BFR/BS) and the
      compression load of the lumbar body increased and the number of osteoclasts
      decreased, but bone mineral density (BMD) and structure did not increase. In the
      mid femur, the cross-sectional area, the cortical bone area, the moment of
      inertia, the periosteal MS/BS, BFR/BS and the bending load increased in the
      exercise group. In 8 weeks, the increases in BMD, structure and load values were
      significant in both the lumbar and mid femur. At both 4 and 8 weeks, the MS/BS
      for the endocortical surface of mid femur were not increased and mineral
      apposition rate (MAR) remained reduced. These results show that jumping exercise
      increases the mass and strength of the lumbar vertebrae and mid femur by
      stimulating bone formation and accelerates cortical drift by both increasing
      periosteal bone formation and reducing the endocortical MAR.

PMID- 10958369
TI  - Muscle and tendon stiffness in patients with upper motor neuron lesion following
      a stroke.
AB  - The objective of this study was to investigate muscle and tendon stiffness in the
      triceps surae muscles in patients who had previously had a stroke. The
      participants were 12 men showing slight to moderate degrees of muscle tonus in
      the affected leg. All patients showed minimal or no overt clinical motor
      symptoms, and all walked without mechanical aid. Muscle strengths in isometric
      and isokinetic activities were measured, as was passive resistance during
      plantarflexion in each leg. Walking speed was also measured. Evaluations of
      physical performance and muscle tone were made. Muscle and tendon stiffness was
      calculated from measurements whilst passively stretching during electrical
      stimulation, separately for each leg. Muscle strength was significantly higher in
      the non-affected than in the affected leg. Muscle stiffness was significantly
      higher in the affected leg than in the non-affected leg. Tendon stiffness was
      significantly higher in the non-affected than in the affected leg. The higher
      muscle stiffness in the affected leg might enhance the possibility for storing
      elastic energy during preactivation. Lower tendon stiffness in the affected leg
      might reduce the development of fatigue in movements at low velocities.

PMID- 10958370
TI  - Coordination-related changes in the rhythms of breathing and walking in humans.
AB  - Coordination of the respiratory rhythm with the rhythm of limb movements has
      often been observed during rhythmical exercise (e.g. in locomotion). It is
      usually associated with changes in the respiratory time course, but not in the
      locomotor rhythm. Therefore, we hypothesised that in walking, the extent of
      coordination-related changes (CRC) in respiratory parameters would increase with
      closer coordination. With respect to the controversially discussed question of a
      possible energetic advantage due to coordination, we devoted particular interest
      to the CRC in oxygen uptake (VO2). In addition, we investigated the incidence and
      the extent of CRC in the stepping rhythm. We examined 18 volunteers walking on a
      treadmill at three different workload levels, which were adjusted by altering
      either the velocity or slope of the treadmill. Each walking test was carried out
      twice, once with spontaneous breathing and once with breathing paced by a step
      related acoustic signal to enhance the coordination between breathing and
      walking. No correlation was found between the CRC in the analysed parameters and
      the degree of coordination. However, the extent of CRC of ventilation and VO2
      decreased with increasing workload. With the transition to coordination,
      increases and decreases of VO2 occurred about equally often. From this we
      conclude that energetic economisation in walking, as reflected by a reduction in
      VO2, is rather a side-effect of coordination, and is probably due to a more
      precise regulation of the breathing pattern. The economisation was more
      pronounced at higher work loads than at lower work loads. Our results revealed
      that coordination is also associated with changes in the stepping rate, which
      occurred more frequently when the variability of breathing was restricted by
      acoustic pacing of the breathing rhythm. This finding suggests that the choice of
      walking rhythm is not completely free, but can be influenced by the breathing
      rhythm. CRC in the walking rhythm might contribute to the avoidance of excessive
      CRC in the respiratory time course, which would entail an inefficient breathing
      pattern and thus, an energetic disadvantage.

PMID- 10958371
TI  - Coactivation of the ankle musculature during maximal isokinetic dorsiflexion at
      different angular velocities.
AB  - The objectives of this study were to determine the differences in the level of
      coactivation among the ankle agonist and antagonist muscles during maximal
      isokinetic dorsiflexion and to determine whether velocity alters the activation
      levels. Raw surface electromyograms (EMG) were recorded from six muscle sites-
      two over the agonist tibialis anterior (upper and lower sites) and four over the
      antagonist (lateral and medial gastrocnemius, plus lateral and medial soleus)
      muscles--in ten healthy subjects (two males and eight females) as they performed
      maximal dorsiflexor efforts against an isokinetic dynamometer at each of three
      angular velocity settings (30, 90 and 150 degrees/s). The root-mean-square
      amplitude (RMS) was calculated over a 35 degree angular displacement for each EMG
      recording, then was normalized (RMS(Nji)) to the amplitude measured during
      maximal voluntary isometric contractions (MVIC) of the dorsifexors and
      plantarflexors (i.e. RMS(MVICj)). A two-factor repeated-measures analysis of
      variance (ANOVA) tested the muscle site by velocity interaction and the main
      effects of muscle site and velocity separately. The raw EMG signals were then
      full-wave rectified and low-pass filtered (6 Hz) and ensemble average curves of
      the sample were calculated, for each muscle site, at each velocity. The ANOVA
      revealed a statistically significant muscle-by-velocity interaction (P < 0.05).
      The RMS(Nji) values for the two tibialis anterior sites were not significantly
      different from each other for any of the three velocity settings, nor for the two
      gastrocnemius muscles at 30 degrees/s velocity. All other between-muscle
      comparisons were statistically significant (P < 0.05). The RMS(Nji) means were
      28, 23, 59, 52, 98 and 98% MVIC for the lateral and medial gastrocnemius, the
      lateral and medial sites on the soleus, and for the upper and lower sites on the
      tibialis anterior, respectively. The RMS(Nji) from the lower site on the tibialis
      anterior yielded the only statistically significant difference (P < 0.05) among
      velocities; at this site, the RMS(Nji) at 150 degrees/s was higher than at the
      other two velocities. The ensemble-average curves revealed that not all muscle
      sites are activated to a consistent level throughout the entire movement. The
      interaction between agonist and antagonist activation during isokinetic
      dorsiflexion has implications for interpreting the results of isokinetic
      dynamometry for strength assessment and for understanding the neuromuscular
      control strategies used in this exercise modality.

PMID- 10958372
TI  - Effects of marathon running on running economy and kinematics.
AB  - The present study was designed to investigate interactions between running
      economy and mechanics before, during, and after an individually run marathon.
      Seven experienced triathletes performed a 5-min submaximal running test on a
      treadmill at an individual constant marathon speed. Heart rate was monitored and
      the expired respiratory gas was analyzed. Blood samples were drawn to analyze
      serum creatine kinase activity (S-CK), skeletal troponin I (sTnI), and blood
      lactate (B-La). A video analysis was performed (200 frames x s(-1)) to
      investigate running mechanics. A kinematic arm was used to determine the external
      work of each subject. The results of the present study demonstrate that after the
      marathon, a standardized 5-min submaximal running test resulted in an increase in
      oxygen consumption, ventilation, and heart rate (P < 0.05), with a simultaneous
      decrease in the oxygen difference (%) between inspired and expired air, and
      respiratory exchange ratio (P < 0.05). B-La did not change during the marathon,
      while sTnI and S-CK values increased (P < 0.05), peaking 2 h and 2 days after the
      marathon, respectively. With regard to the running kinematics, a minor increase
      in stride frequency and a similar decrease in stride length were observed (P <
      0.01). These results demonstrate clearly that weakened running economy cannot be
      explained by changes in running mechanics. Therefore, it is suggested that the
      increased physiological loading is due to several mechanisms: increased
      utilization of fat as an energy substrate, increased demands of body temperature
      regulation, and possible muscle damage.

PMID- 10958373
TI  - Short-term recovery from prolonged constant pace running in a warm environment:
      the effectiveness of a carbohydrate-electrolyte solution.
AB  - Recovery from prolonged exercise involves both rehydration and replenishment of
      endogenous carbohydrate stores. This study examined the influence of drinking a
      carbohydrate-electrolyte solution on short-term recovery and subsequent exercise
      capacity in a warm environment. Thirteen healthy male volunteers completed two
      trials, at least 7 days apart. On each occasion subjects performed an initial
      treadmill run at 60% of maximal oxygen uptake (VO2max), for 90 min or until
      volitional fatigue (T1), in a warm environment (35 degrees C, 40% relative
      humidity, RH). Volitional ingestion of water was permitted during each of the
      exercise trials. During a subsequent 4-h recovery period (REC) subjects consumed
      either a 6.9% carbohydrate-electrolyte solution (CES) or a sweetened placebo (P),
      in a volume equivalent to 140% of body mass loss. Following REC, subjects ran to
      exhaustion at the same % VO2max in order to assess their endurance capacity (T2).
      Mean (SEM) run times during T1 did not differ between the CES [74.8 (4.6) min]
      and P [72.5 (5.2) min] trials. Body mass was reduced (P < 0.01) by 1.9 (0.2)%
      (CES) and 1.7 (0.2)% (P), and plasma volume (P < 0.01) by 6.0 (0.9)% (CES) and
      5.4 (1.0)% (P) during the T1 trials. During REC 2006 (176) ml and 1830 (165) ml
      of fluid was ingested, providing 138 (12) g and 0 g of carbohydrate in the CES
      and P trials, respectively. Prior to T2, plasma volume and net fluid balance were
      similarly restored [CES +58 (26) g; P -4 (68) g] in both trials. During T2 the
      exercise duration was longer (P < 0.01) in the CES compared to the P trial [CES
      60.9 (5.5) min; P 44.9 (3.0) min]. Thus, provided that an adequate hydration
      status is maintained, inclusion of carbohydrate within an oral rehydration
      solution will delay the onset of fatigue during a subsequent bout of prolonged
      submaximal running in a warm environment.

PMID- 10958374
TI  - A new impedance cardiograph device for the non-invasive evaluation of cardiac
      output at rest and during exercise: comparison with the "direct" Fick method.
AB  - The objectives of this study were to evaluate the reliability and accuracy of a
      new impedance cardiograph device, the Physio Flow, at rest and during a steady
      state dynamic leg exercise (work intensity ranging from 10 to 50 W) performed in
      the supine position. We compared cardiac output determined simultaneously by two
      methods, the Physio Flow (QcPF) and the direct Fick (QcFick) methods. Forty
      patients referred for right cardiac catheterisation, 14 with sleep apnoea
      syndrome and 26 with chronic obstructive pulmonary disease, took part in this
      study. The subjects' oxygen consumption values ranged from 0.14 to 1.19 l x min(
      1). The mean difference between the two methods (QcFick - QcPF) was 0.04 l x min(
      1) at rest and 0.29 l x min(-1) during exercise. The limits of agreement, defined
      as mean difference +/- 2SD, were -1.34, +1.41 l x min(-1)] at rest and -2.34,
      +2.92 l x min(-1) during exercise. The difference between the two methods
      exceeded 20% in only 2.5% of the cases at rest, and 9.3% of the cases during
      exercise. Thoracic hyperinflation did not alter QcPF. We conclude that the Physio
      Flow provides a clinically acceptable and non-invasive evaluation of cardiac
      output under these conditions. This new impedance cardiograph device deserves
      further study using other populations and situations.

PMID- 10958376
TI  - The effect of age on the power/duration relationship and the intensity-domain
      limits in sedentary men.
AB  - The time to fatigue (t) in response to high-intensity constant-load exercise
      decreases hyperbolically with increasing power (W), at least in active and
      younger individuals [i.e. (W - thetaF)t = W', where thetaF is the critical power
      asymptote and W' is the curvature constant]. Little is known, however, about the
      combined effects of age and sedentarity on these parameters. We therefore
      evaluated 17 non-trained males (9 aged 60-75 years and 8 aged below 30 years) who
      underwent ramp-incremental cycle ergometry and, on different days, 4 high
      intensity constant-load tests to t. Compared to their younger counterparts, the
      older subjects presented significantly lower maximum oxygen uptake (i.e. the
      maximum value of oxygen uptake attained at the end of a progressive exercise with
      the subject exerting a presumably maximal effort, muVO2), estimated lactate
      threshold (VO2thetaL), VO2thetaF, and W' (P < 0.05). Interestingly, however, both
      VO2thetaL and VO2thetaF, when expressed as a percentage of muVO2, were higher in
      older than in younger men [61.8 (6.2)% versus 45.4 (4.6)% and 87.8 (7.3)% versus
      79.0 (8.2)%, P < 0.05, respectively]. Therefore, age was associated with an
      increase in the relative magnitude of the "moderate", sub-thetaL exercise
      intensity domain (+30.4%), mainly at the expense of the "very-heavy", supra
      thetaF domain (-56%). Our results demonstrate that age and sedentarity are
      associated with: (1) marked reductions in both the aerobic (thetaF) and anaerobic
      (W') determinants of the W/t relationship, and (2) changes in either the absolute
      or relative magnitudes of the exercise-intensity domains. These findings are
      consistent with the notion that endurance-related parameters are less diminished
      with ageing than the maximal capacity, thereby mitigating the deleterious effects
      of senescence in the functional capacity.

PMID- 10958375
TI  - Effect of creatine feeding on maximal exercise performance in vegetarians.
AB  - The effect of creatine supplementation on exercise performance in vegetarians was
      examined. Creatine was ingested for 1 week by a group of vegetarians (VC) and
      meat-eaters (MC); a control group of meat-eaters was fed only glucose (MG).
      Exercise performance during three, 20-s maximal cycling tests (modified Wingate
      anaerobic test, WAnT) was determined before and after creatine supplementation.
      Blood samples were also drawn before and after exercise prior to and after
      supplementation. Basal plasma creatine (after an overnight fast) averaged (SE) 11
      (2) microM in VC, and 24 (2) and 23 (7) microM in MG and MC, respectively (P <
      0.05 for VC vs meat-eaters). These findings were expected, since most of the
      body's exogenous creatine source is meat. There was no significant difference in
      any other parameter between groups prior to supplementation. Creatine feedings
      significantly increased body mass (approximately 1 kg) and mean power output
      during the WAnTs (approximately 5%) to a similar extent in the VC and MC groups
      (P < 0.05-0.001). These parameters were not affected by supplementation in the MG
      group. Peak power output was also significantly increased by supplementation in
      MC (approximately 5%, P < 0.05), but not in VC. It is concluded that vegetarians
      and meat-eaters respond to creatine feedings with similar increases in mean power
      output during short-term, maximal exercise.

PMID- 10958377
TI  - The effect of nitrous oxide-induced narcosis on aerobic work performance.
AB  - Previous findings of a narcosis-induced reduction in heat production during cold
      water immersion, as reflected in oxygen uptake (VO2), have been attributed to the
      attenuation of the shivering response. The possibility of reduced oxygen
      utilization (VO2) by the muscles could not, however, be excluded. Accordingly,
      the present study tested the hypothesis that mild narcosis, induced by inhalation
      of a normoxic gas mixture containing 30% nitrous oxide (N2O), would affect VO2.
      Nine male subjects participated in both maximal and submaximal exercise trials,
      inspiring either room air (AIR) or a normoxic mixture containing 30% N2O. In the
      submaximal trials, the subjects exercised at 50% of maximal exercise intensity
      (Wmax) as determined in the maximal AIR trial. Though the subjects attained the
      same Wmax in the AIR and N2O trials, maximal VO2 was significantly higher (P <
      0.05) during the N2O condition [58.9 (SEM 3.1) ml x kg(-1) x min(-1)] compared to
      the AIR condition [55.0 (SEM 2.4) ml x kg(-1) x min(-1)]. However, the VO2
      relative exercise intensity relationship was similar during both maximal AIR and
      maximal N2O at submaximal exercise intensities. There were no significant
      differences in the responses of oesophageal temperature, sweating rate, heart
      rate and ventilation between AIR and N2O in the maximal and submaximal tests. It
      was concluded that the previously reported narcosis-induced reductions in VO2
      observed during cold water immersion can be attributed solely to a reduction in
      the shivering response rather than to decreased oxygen utilization by the
      muscles.

PMID- 10958378
TI  - Cardiorespiratory responses to fatiguing dynamic and isometric hand-grip
      exercise.
AB  - In occupational work, continuous repetitive and isometric actions performed with
      the upper extremity primarily cause local muscle strain and musculoskeletal
      disorders. They may also have some adverse effects on the cardiorespiratory
      system, particularly, through the elevation of blood pressure. The aim of the
      present study was to compare peak cardiorespiratory responses to fatiguing
      dynamic and isometric hand-grip exercise. The subjects were 21 untrained healthy
      men aged 24-45 years. The dynamic hand-grip exercise (DHGE) was performed using
      the left hand-grip muscles at the 57 (SD 4)% level of each individual's maximal
      voluntary contraction (MVC) with a frequency of 51 (SD 4) grips x min(-1). The
      isometric hand-grip exercise (IHGE) was done using the right hand at 46 (SD 3)%
      of the MVC. The endurance time, ventilatory gas exchange, heart rate (HR) and
      blood pressure were measured during both kinds of exercise. The mean endurance
      times for DHGE and IHGE were different, 170 (SD 62) and 99 (SD 27) s,
      respectively (P < 0.001). During DHGE the mean peak values of the breathing
      frequency [20 (SD 6) breaths x min(-1)] and tidal volume [0.89 (SD 0.34) l]
      differed significantly (P < 0.01) from peak values obtained during IHGE [15 (SD
      5) breaths x min(-1) and 1.14 (SD 0.32) l, respectively]. The corresponding peak
      oxygen consumptions, pulmonary ventilations, HR and systolic blood pressures did
      not differ, and were 0.51 (SD 0.06) and 0.46 (SD 0.11) l x min(-1), 17.1 (SD 3.0)
      and 16.7 (SD 4.7) l x min(-1), 103 (SD 18) and 102 (SD 17) beats x min(-1), and
      156 (SD 17) and 161 (SD 17) mmHg, respectively. The endurance times of both DHGE
      and IHGE were short (< 240 s). The results indicate that the peak responses for
      the ventilatory gas exchange, HR and blood pressure were similar during fatiguing
      DHGE and IHGE, whereas the breathing patterns differed significantly between the
      two types of exercise. The present findings emphasize the importance of following
      ergonomic design principles in occupational settings which aim to reduce the
      output of force, particularly in tasks requiring isometric and/or one-sided
      repetitive muscle actions.

PMID- 10958379
TI  - Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes
      by anti-allergic agents in vitro.
AB  - The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium
      cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using
      in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days
      after immunization with haemocyanin absorbed to aluminium hydroxide were cultured
      in the presence of 100.0 microg/ml haemocyanin and various concentrations of the
      agents. Low concentrations (<1.5 x 10(-4)M) of EP and DSCG did not influence
      spleen cell blastic activity induced by antigenic stimulation, whereas these
      agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M
      of the agents were added to cell cultures. EP and DSCG also did not affect
      blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody
      stimulation even when these cells were cultured in the presence of 2 x 10(-4) M
      of the agents. We next examined the influence of EP and DSCG on the expression of
      co-stimulatory molecules on spleen cells in response to antigenic stimulation.
      Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the
      agents and the expression of molecules were examined by flow cytometer 24h later.
      EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80,
      but not CD86, on splenic B cells which were enhanced by antigenic stimulation in
      vitro.

PMID- 10958380
TI  - The inhibitory effect of anti-allergic agent suplatast tosilate (IPD-1151T) on
      methacholine- and allergen-induced bronchoconstriction in sensitized mice.
      asakazu@med.showa-u.dc.jp.
AB  - The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (+/-)-[2
      [4-(3-ethoxy-2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p
      toluenesulfonate) on allergic bronchoconstriction induced by allergen and
      methacholine (MCh) were examined in mice. BALB/c mice were sensitized by
      intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP
      KLH) mixed with A1(OH)3 (DNP-KLH). IPD-1151T was administered orally once a day
      for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was
      measured 24h after the final drug administration. IPD-1151T inhibited both
      antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The
      inhibition induced was closely related to the dose and frequency of oral
      administration of the agent. We also examined the effect of IPD-1151T on IgE
      production in response to DNP-KLH immunization. IPD-1151T inhibited dose
      dependently both total and specific IgE concentrations in serum prepared from
      mice 15 days after immunization. These results strongly indicate that IPD-1151T
      inhibits IgE production in vivo and results in attenuating effect on
      bronchoconstriction.

PMID- 10958382
TI  - Human eosinophil-airway smooth muscle cell interactions.
AB  - Eosinophils are present throughout the airway wall of asthmatics. The nature of
      the interaction between human airway smooth muscle cells (ASMC) and eosinophils
      was investigated in this study. We demonstrated, using light microscopy, that
      freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro.
      Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by
      20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1,
      and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24h with TNF-alpha,
      10 nM, significantly increased eosinophil adhesion to 149 and 157% of control
      after 2 and 20 h. These results provide evidence that eosinophil interactions
      with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-alpha.

PMID- 10958383
TI  - Local haemorrhage induced by Bothrops jararaca venom: relationship to neurogenic
      inflammation.
AB  - We investigated morphological alterations induced by s.c. injection of 2.5 microg
      of Bothrops jararaca venom in rats. Intense disorganisation of collagen fibres
      was observed 1 min after the venom injection, particularly at regions near
      vessels and nerves. Mast cells were degranulated, and erythrocytes were seen
      leaving venules throughout the endothelial junctions. At this time, damaged
      endothelial cells were not observed. In rats envenomed as above, but immediately
      after cardiorespiratory failure induced by deep ether anaesthesia, alterations in
      the connective tissue structures, as previously described, were not observed. The
      mediation of this haemorrhage was investigated by injecting the venom into the
      foot pad of mice and compared to the mediation of oedema. Local haemorrhage was
      significantly reduced in mice pre-treated with capsaicin or guanethidine or
      submitted to a surgical section of sciatic and saphenous nerves. In these
      animals, oedema was not affected. Groups treated with methysergide or morphine
      showed both haemorrhage and oedema significantly reduced. Indomethacin or
      dexamethasone pre-treatments significantly reduced the oedema, but not the
      haemorrhage. Moreover, in animals treated with promethazine or mepyramine, oedema
      and haemorrhage were not affected. These data suggest that local haemorrhage
      induced by Bothrops jararaca venom is partially controlled by serotonin and
      neurohumoral mediators. Furthermore, results indicate that haemorrhage and oedema
      are mediated by different pharmacological systems.

PMID- 10958386
TI  - Letter from the editor: PACS vobiscum

PMID- 10958381
TI  - Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast
      proliferation, chemotactic response and matrix metalloproteinases activity.
AB  - Fibroblast migration, proliferation, extracellular matrix protein synthesis and
      degradation are the key events in various biological and pathological processes
      in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients
      with pulmonary fibrosis show increased numbers of mast cells which have
      metachromatic granules containing heparin, histamine and proteases. Little is
      known about how these products influence pulmonary fibrosis. In the present
      study, we investigated the effect of heparin and related glycosaminoglycans on
      PDGF-induced lung fibroblast proliferation and chemotactic response in vitro. In
      addition, we examined the effect of heparin on both the induction of matrix
      metalloproteinases (MMPs) and MMPs activity in lung fibroblasts in vitro.
      Heparin, de-N-sulphated heparin but not heparan sulphate inhibited PDGF-induced
      lung fibroblast proliferation. In contrast, only heparin inhibited PDGF
      stimulated human lung fibroblast chemotaxis. Negatively charged poly-L-glutamic
      acid had no effect on either fibroblast proliferation or chemotaxis. Thus the
      negative charge alone cannot account for the ant-proliferative and anti
      chemotactic effects of heparin. Furthermore, heparin and heparan sulphate also
      had no inhibitory effect on induction of MMPS, including MMP-1 (interstitial
      collagenase), MMP-2 (gelatinase A) and MMP-9 (gelatinase B). Only heparin
      inhibited both MMP-1 and MMP-2/MMP-9 activity. Additionally, tissue inhibitor of
      metalloproteinase type 1 (TIMP-1) and type 2 (TIMP-2) inhibited PDGF-stimulated
      human lung fibroblast chemotaxis. The ability of heparin to inhibit fibroblast
      chemotaxis may account for the inhibitory effect of heparin on MMP activity. The
      above results suggested that heparin and related glycosaminoglycans
      differentially regulate PDGF-induced lung fibroblast proliferation, chemotaxis
      and MMPs activity and further that these effects may have a key role in
      extracellular matrix remodeling in inflammatory lung disease.

PMID- 10958384
TI  - Effect of an inhaled glucocorticoid on reactive oxygen species production by
      bronchoalveolar lavage cells from smoking COPD patients.
AB  - Oxidative stress in the lung is important in the pathogenesis of COPD. Published
      data indicate that glucocorticoids inhibit blood cells in their capacity to
      produce reactive oxygen species (ROS). We investigated the effect of Fluticasone
      propionate (FP) on the ROS production capabilities of pulmonary cells.
      Bronchoalveolar lavage (BAL) was performed in smoking COPD patients, before and
      after a six month, placebo-controlled treatment with FP. BAL cells were
      stimulated with phorbol myristrate acetate (PMA) alone, and together with
      superoxide dismutase (SOD). From kinetic plots of ferricytochrome-c conversion we
      calculated the maximal rate of superoxide production: V(max). We also examined
      BAL cell subsets and performed correlation analyses on ROS production and
      relevant clinical determinants. Paired results were obtained from 6 FP- and 9
      placebo-treated patients. No significant change of V(max) was found in both
      patient groups. Also BAL cellularity was unchanged. Correlation analyses showed a
      significant (inverse) association of V(max) with the number of cigarettes smoked
      per day. We concluded that a potent inhaled glucocorticoid had no effect on the
      ROS production capability of BAL cells from smoking COPD patients. Apparently,
      heavy smoking impaired the ability of alveolar macrophages to produce ROS, which
      was not further decreased by FP.

PMID- 10958387
TI  - Three-dimensional morphology of cerebellar climbing fibers. A study by means of
      confocal laser scanning microscopy and scanning electron microscopy.
AB  - The intracortical pathway of cerebellar climbing fibers have been traced by means
      of scanning electron microscopy (SEM) and confocal laser scanning microscopy
      (CLSM) to study the degree of lateral collateralization of these fibers in the
      granular Purkinje cell and molecular layers. Samples of teleost fish were
      processed for conventional and freeze-fracture SEM. Samples of hamster cerebellum
      were examined by means of CLSM using FM4-64 as an intracellular stain. High
      resolution in lens SEM of primate cerebellar cortex was carried out using
      chromium coating. At scanning electron and confocal laser microscopy levels, the
      climbing fibers appeared at the white matter and granular layer as fine fibers
      with a typical arborescence or crossing-over branching pattern, whereas the mossy
      fibers exhibited a characteristic dichotomous bifurcation. At the granular layer,
      the parent climbing fibers and their tendrils collaterals appeared to be
      surrounding granule and Golgi cells. At the interface between granule and
      Purkinje cell layers, the climbing fibers were observed giving off three types of
      collateral processes: those remaining in the granular layer, others approaching
      the Purkinje cell bodies, and a third type ascending directly to the molecular
      layer. At this layer, retrograde collaterals were seen descending to the granular
      layer. By field emission high-resolution SEM of primate cerebellar cortex, the
      climbing fiber terminal collaterals were appreciated ending by means of round
      synaptic knobs upon the spines of secondary and tertiary Purkinje cell dendrites.

PMID- 10958389
TI  - Semiconductor devices "from inside"
AB  - Operation of any semiconductor device can be presented by unique configuration of
      the electrical field (potential) and charge (doping) distribution within the
      device. More specifically, the status of operation is described by the quasi
      Fermi energy (QFE) profile across the device. Visualization of the dynamic
      operation of the device and quantitative measurements of the QFE profile is
      provided by differential voltage contrast (DVC), which is a modification of the
      secondary electron imaging in a scanning electron microscope (SEM). The DVC
      consists of storing two images of a tested semiconductor device. Exposed to the
      electron beam is a cross section, for example, of a field effect transistor
      (FET). The first image, covering the entire inside of the FET from source to
      drain, is taken when the device is not biased. The second image of the same area
      is taken when the transistor is biased. The secondary electron signal is enhanced
      or retarded by actual distribution of a potential across the tested device.
      Subtraction pixel by pixel of the two carefully aligned images removes
      morphologic contrast from the screen, takes away surface features and
      contamination of the sample, and reveals the contribution of the electrical field
      to the changes of contrast. The calibration procedure allows measurement of the
      potential distribution with a precision of 0.05 V. The first derivative of a
      potential profile provides for distribution of the electrical field and the
      second derivative gives the doping profile across the tested device. A variety of
      semiconductor devices such as p-n junctions, Zener diodes, MOSFET's, MESFET's,
      solar cells and optical detectors, quantum well lasers, etc., were tested.
      Videotaping of the tested devices allows us to observe the changes in the
      electrical field and charge distribution as the device operates in a wide range
      of electrical or optical signals.

PMID- 10958385
TI  - Th1 and Th2 cytokine profile in patients with early onset periodontitis and their
      healthy siblings.
AB  - Early onset periodontitis (EOP) is a chronic inflammatory periodontal disease
      with a strong genetic link affecting individuals aged 17 to 25. In the familial
      studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the
      pathogenesis of EOP disease. The study involved 6 individuals with EOP disease
      and their 6 siblings with healthy periodontium. Actinobacillus
      actinomycetemcomitans (A. a), a bacterium typical for EOP, was detected in all
      people studied. Th1 and Th2 cytokine production was measured after in vitro
      stimulation. Peripheral blood mononuclear cells (PBMC) were isolated and
      cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of
      IL-4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro
      stimulation of PBMC, a significantly higher production of IL-4 and significantly
      lower production of IFN-gamma were found in the group of patients compared with
      their healthy siblings. The increased level of IL-4 in patients was in good
      agreement with an increased level of IgM after stimulation of lymphocytes with E.
      coli. These results support Seymour's hypothesis according to which patients with
      progressive disease primarily activate Th2 lymphocytes while non-susceptible
      individuals activate Th1 lymphocytes.

PMID- 10958388
TI  - Three-dimensional microscopy data exploration by interactive volume
      visualization.
AB  - This paper presents a new volume visualization approach for three-dimensional (3
      D) interactive microscopy data exploration. Because of their unique image
      characteristics, 3-D microscopy data are often not able to be visualized
      effectively by conventional volume visualization techniques. In our approach,
      microscopy visualization is carried out in an interactive data exploration
      environment, based on a combination of interactive volume rendering techniques
      and image-based transfer function design methods. Interactive volume rendering is
      achieved by using two-dimensional (2-D) texture mapping in a Shear-Warp volume
      rendering algorithm. Image processing techniques are employed and integrated into
      the rendering pipeline for the definition and searching of appropriate transfer
      functions that best reflect the user's visualization intentions. These techniques
      have been implemented successfully in a prototype visualization system on low-end
      and middle-range SGI desktop workstations. Since only 2-D texture mapping is
      required, the system can also be easily ported to PC platforms.

PMID- 10958390
TI  - Charge contrast imaging of material growth and defects in environmental scanning
      electron miscroscopy--linking electron emission and cathodoluminescence
AB  - An electron-based technique for the imaging of crystal defect distribution such
      as material growth histories in non- and poorly conductive materials has been
      identified in the variable pressure or environmental scanning electron
      microscope. Variations in lattice coherence at the meso-scale can be imaged in
      suitable materials. Termed charge contrast imaging (CCI), the technique provides
      images that correlate exactly with emitted light or cathodoluminescence in
      suitable materials. This correlation links cathodoluminescence and an electron
      emission. The specific operating conditions for observation of these images
      reflect a complex interaction between the electron beam, the positive ions
      generated by electron-gas interactions in the chamber, a biased detector, and the
      sample. The net result appears to be the suppression of all but very near surface
      electron emission from the sample, probably from of the order of a few
      nanometres. Consequently, CCI are also sensitive to very low levels of surface
      contaminants. Successful imaging of internal structures in a diverse range of
      materials indicate that the technique will become an important research tool.

PMID- 10958391
TI  - Thermal effects of the electron beam and implications of surface damage in the
      analysis of bone tissue.
AB  - Electron beam interactions with specimens in the scanning electron microscope
      (SEM) can lead to increased surface temperatures and damage. These changes may
      have significant consequences in the analysis of bone tissue. An investigation
      was performed to measure the surface temperature changes associated with the
      electron beam on a thermocouple with systematic variations in operating
      conditions. Probe currents, magnifications, and accelerating voltages were
      incrementally adjusted to measure the temperature changes and to make assessments
      for determining optimal operating conditions for the SEM in future analyses of
      bone tissue. Results from this study suggest that thermal effects were minimal at
      lower accelerating voltages (< 20 kV), lower probe currents (< 10 nA), and lower
      magnifications, but surface damage may still occur during the analysis of bone
      tissue.

PMID- 10958393
TI  - High-resolution scanning electron microscopy study of sputtered nanolaminated
      Ti/TiN multilayers
AB  - This work presents the morphologic and structural study of nanolaminated Ti/TiN
      multilayers using high-resolution scanning electron microscopy (HR-SEM), coupled
      to x-ray reflectometry (XRR). The multilayers have been deposited by reactive rf
      sputtering on silicon substrates. For large period thickness (lambda=40 nm, 10
      periods), in XRR, the low number of interfaces makes the interference less
      structured. An experimental pattern with broad and weakly intense Braggs peaks is
      obtained, but is difficult to simulate. On the other hand, HR-SEM observation of
      cross sections gives excellent pictures of the multilayer, so that precise
      measurements of the thickness can be achieved: a 42 nm thick period is observed,
      formed with 17 nm of Ti and with 25 nm of TiN. For small (Ti+TiN) period
      thickness (lambda=2.5 nm, 120 periods), the XRR pattern exhibits intense and
      narrow Bragg peaks: the number of interfaces is sufficient to structure the
      interference and an intense signal is obtained. The best fit of simulation is
      obtained for a 2.6 nm thin period, made of 0.9 nm of Ti and 1.7 nm of TiN. No
      laminated structure has been observed by cross-section HR-SEM observation because
      its resolution (around 2 nm at 10 kV) is larger than the layer thickness in a
      period. High-resolution SEM and XRR are thus two complementary techniques for the
      routine characterization of multilayers.

PMID- 10958392
TI  - Three-dimensional reconstruction and motion analysis of living, crawling cells.
AB  - Cell behavior is three-dimensional (3-D), even when it takes place on a flat
      surface. Migrating cells form pseudopods on and off the substratum, and the cell
      body undergoes height changes associated with a 1 min behavior cycle. Inside the
      cell, the nucleus has a 3-D migratory cycle, and vesicles move up and down in the
      z-axis as a cell locomotes. For these reasons, the two-dimensional (2-D) analysis
      of cellular and subcellular behavior is, in many cases, inadequate. We have,
      therefore, developed 3-D motion analysis systems that reconstruct the cell
      surface, nucleus, pseudopods, and vesicles of living, crawling cells in 3-D at
      time intervals as short as 1 s, and compute more than 100 parameters of motility
      and dynamics morphology at 1-s intervals. We are now in the process of developing
      a multimode reconstruction system that will allow us to reconstruct and analyze
      fluorescently tagged molecular complexes within the differential interference
      contrast-imaged subcellular architecture of a crawling cell. These evolving
      technologies should find wide application for a host of biomedical problems.

PMID- 10958394
TI  - Ultrastructure and reproduction behaviour of single CHO-K1 cells exposed to near
      infrared femtosecond laser pulses.
AB  - In the present work, the authors investigated ultrastructural changes as well as
      the reproduction behaviour of preselected single CHO-K1 cells exposed to 170
      femtosecond laser pulses at different power output levels in comparison with
      cells outside the illumination volume. The ultrashort laser pulses were provided
      by an 80 MHz Ti:sapphire laser at 780 nm. The cells were scanned ten times with a
      scan rate of 1/16 s(-1). Single CHO-K1 cells exposed to low mean power of 2 mW
      revealed no significant changes in ultrastructure after laser exposure. In some
      cases, changes of mitochondria with slight disordering of cristae were found.
      Cytoplasm was filled with vesicles that seemed to be released from Golgi stacks.
      Cells irradiated with higher powers demonstrated more dramatic changes in
      ultrastructure. A considerable number of swollen mitochondria in conjunction with
      loss of cristae was observed. The main event of mitochondrial changes was the
      formation of electron dense bodies in the mitochondrial matrix. In addition,
      lumen of endoplasmatic reticulum was enlarged. Highest applied mean laser power
      of 12.5 mW lead to complete destruction of mitochondria and their transformation
      to electron dense structures containing membrane material. Compared with cell
      targets irradiated with 2 mW mean power, the release of vesicles from Golgi
      stacks seemed to be rather moderate. Cells localised outside the laser beam
      revealed no ultrastructural changes. Low mean laser power at 2 mW was unable to
      impair the reproduction behaviour of CHO-K1 cells. At higher laser power output
      levels, CHO-K1 cells started to delay cell division. At 12.5 mW, no cell division
      occurred. The obtained results may be helpful in recommending parameters for safe
      femtosecond laser microscopy of living specimens.

PMID- 10958395
TI  - The role of partial laryngeal resection in current management of laryngeal
      cancer: a collective review.
AB  - A spectrum of treatment plans and surgical procedures is available for management
      of early and moderately advanced laryngeal cancer. While the approach of
      chemotherapy and irradiation, or irradiation alone, followed by total
      laryngectomy for failure is often employed in practice by present day clinicians,
      the options of conventional conservation surgery (CCS), transoral endoscopic
      laser surgery (TLS) and supracricoid partial laryngectomy (SCPL) provide a wide
      choice of treatments that may help attain the goal of cure with preservation of
      laryngeal function and integrity of the airway. While CCS has been supplanted for
      many early-stage lesions by TLS and for more advanced stages by SCPL, centres
      throughout the world have reported favourable results with CCS, which is often
      modified to include resection of more extensive tumours than was previously
      possible. During the past decade a number of extended CCS procedures have been
      developed for management of glottic tumours involving both vocal cords and the
      anterior commissure, the paraglottic space and with vocal cord fixation, and for
      supraglottic tumours involving the glottis or hypopharynx. TLS has proved an
      effective, minimally invasive and functionally satisfactory procedure for
      management of suitable T1 and T2 glottic cancers, and stage I-III supraglottic
      cancers. The procedure may be effectively employed in combination with neck
      dissection and postoperative radiotherapy when necessary, particularly for
      moderately advanced supraglottic carcinomas. SCPL has proven effective in
      management of glottic and supraglottic cancers of all stages, even with
      involvement of paraglottic space and thyroid cartilage, provided at least one
      arytenoid unit can be preserved with clear margins. Invasion of cricoid cartilage
      is the most significant limitation for this procedure. All three surgical
      approaches have been employed for irradiation failure, but with greatly increased
      failure and complication rates compared with the results of treatment of non
      irradiated patients. Thus a decision to treat laryngeal cancer initially with
      irradiation may preclude a satisfactory result from partial laryngectomy should
      radiation fail. The treatment of laryngeal cancer should be individualized
      according to the size and extent of the tumour, the age and physical condition of
      the patient, and the skill and experience of the surgeon with various treatment
      modalities and surgical procedures.

PMID- 10958396
TI  - Glutamate-induced production of nitric oxide in guinea pig vestibular sensory
      cells.
AB  - Glutamate-induced production of nitric oxide (NO) in the vestibular organ of the
      guinea pig was investigated using the new fluorescence indicator, DAF-2DA, for
      direct detection of NO. Utricular maculae and isolated vestibular sensory cells
      were examined to locate NO production sites. The fluorescence intensity of the
      sensory cells was augmented by stimulation with glutamate, NMDA and AMPA. This is
      the first direct evidence of NO production in the vestibular end organs. NO may
      play an important role in the glutamate-induced ototoxicity and also be involved
      in disease of the inner ear.

PMID- 10958398
TI  - Electrocochleography in the diagnosis of Meniere's disease.
AB  - This study prospectively analyses electrocochleography (ECoG) recordings obtained
      from ears demonstrating symptoms highly suggestive of Meniere's disease.
      Comparison is made with ECoG recording from ears in which the diagnosis of
      Meniere's is considered unlikely (control ears). Electrocochleograph recordings
      were made through a transtympanic recording needle, situated in the round window
      niche. Analysis was made of the 1 kHz tone burst summation potential (SP) and the
      summation potential:action potential (SP/AP) ratio response to a 90 dB click. All
      patients were prospectively awarded a Meniere's score based on a 10-point scale,
      and comparison was made between ears awarded a score of 7 or greater (Meniere's
      ears; n > 500), and ears awarded a score 3 or less (control ears; n > 900).
      Results demonstrate a significant difference in the 1 kHz SP response, and the
      SP/AP ratio, between "control" and "Meniere's" ears. Furthermore, we show that SP
      negativity is proportional to the amplitude of the AP click response, and in
      patients producing an AP click amplitude exceeding 10 V, sensitivity of the tone
      burst test approaches 85%. This study provides further evidence suggesting the
      useful role of electrocochleography in determining a diagnosis of endolymphatic
      hydrops. and demonstrates improved sensitivity of the 1 kHz SP response, compared
      with SP/AP click ratio, in the diagnosis of Meniere's disease.

PMID- 10958397
TI  - Cerebellopontine angle cisternal infusion of NGF, BDNF and NT-3: effects on
      cochlear neurons disconnected from central target, cochlear nucleus. An in vivo
      quantitative study.
AB  - Cochlear neurons need their synaptic contacts with both their peripheral (organ
      of Corti) and central (cochlear nucleus) targets for survival. We examined the in
      vivo effectiveness of the neurotrophins (NGF, BDNF and NT-3) on cochlear neuronal
      survival using our in vivo model, in which the central connection alone was
      selectively and quantitatively interrupted. The particular neurotrophins
      evaluated in the present study did not appear to have cochlear nerve rescue
      potential. However, the experimental model reported here can serve as a useful
      tool to investigate cochlear neuronal degeneration from the central side, which
      may lead to identification of effective mediators in the future.

PMID- 10958399
TI  - Alpha and beta subunits of acetylcholine receptors in the human inner ear.
AB  - The localization and distribution of nicotinic acetylcholine receptors (n-ACh-r)
      was characterized by studying alpha and beta subunits in the adult human inner
      ear by FITC fluorescence technique. In the cochlea, distinct fluorescence
      staining occurred for beta subunits in outer hair cells (OHCs), but no alpha
      subunits were identified. Beta subunits differ quantitatively between the three
      rows of OHCs, decreasing along a base-to-apex gradient in the cochlea. Both alpha
      and beta subunits were identified on spiral ganglion cells, adjacent nerve fibres
      and in vestibular hair cells (HCs). It would appear that they form an active
      complex in n-ACh-r at these locations.

PMID- 10958401
TI  - Direction of galvanically-induced vestibulo-postural responses during active and
      passive neck torsion.
AB  - The direction of a postural response induced by galvanic vestibular stimulation
      depends on the head and trunk position. The relative importance of afferent
      information (proprioception) and efferent motor command/corollary discharge is
      unknown. We studied the direction of body sway evoked by galvanic vestibular
      stimulation in 9 healthy subjects during active and passive head positioning at 0
      degrees frontal position, 35 degrees to the left, and 75 degrees to the right,
      using a custom-built collar. At 0 degrees and 75 degrees there were no
      significant differences in sway direction between active and passive head
      positioning. The galvanic stimulation invoked sway toward the anode, mainly in
      the inter-aural direction. The sway direction differed significantly between
      active and passive positioning at 35 degrees to the side (p < 0.05). When the
      head was actively kept in this position, the body sway was mainly in an inter
      aural direction. The sway shifted to a naso-occipital direction when the head was
      passively positioned at 35 degrees. Our results indicate that the afferent
      proprioceptive information has the largest influence on the direction of the
      galvanically-induced postural response, although some dependence on efferent
      motor commands and non-linear cervical proprioception cannot be ruled out
      entirely.

PMID- 10958400
TI  - Changes in ribbon synapses and rough endoplasmic reticulum of rat utricular
      macular hair cells in weightlessness.
AB  - This study combined ultrastructural and statistical methods to learn the effects
      of weightlessness on rat utricular maculae. A principle aim was to determine
      whether weightlessness chiefly affects ribbon synapses of type II cells, since
      the cells communicate predominantly with branches of primary vestibular afferent
      endings. Maculae were microdissected from flight and ground control rat inner
      ears collected on day 13 of a 14-day spaceflight (F13), landing day (R0) and day
      14 postflight (R14) and were prepared for ultrastructural study. Ribbon synapses
      were counted in hair cells examined in a Zeiss 902 transmission electron
      microscope. Significance of synaptic mean differences was determined for all hair
      cells contained within 100 section series, and for a subset of complete hair
      cells, using SuperANOVA software. The synaptic mean for all type II hair cells of
      F13 flight rats increased by 100%, and that for complete cells by 200%. Type I
      cells were less affected, with synaptic mean differences statistically
      insignificant in complete cells. Synapse deletion began within 8 h upon return to
      Earth. Additionally, hair cell laminated rough endoplasmic reticulum of flight
      rats was reversibly disorganized on R0. Results support the thesis that synapses
      in type II hair cells are uniquely affected by altered gravity. Type II hair
      cells may be chiefly sensors of gravitational and type I cells of translational
      linear accelerations.

PMID- 10958402
TI  - The effect of stress application on vestibular compensation.
AB  - It is still unknown how stress, which is known to delay recovery from vestibular
      symptoms in patients with vertigo, influences recovery from vertigo. We therefore
      investigated the effect of stress on vestibular compensation following unilateral
      labyrinthectomy (UL) as a model of recovery from vertigo. In addition, we
      examined the effect of trilostane (4alpha, 5-epoxy-17beta-hydroxy-3-oxo-5alpha
      androstane-2alpha-carbon itrile; TRIL), an inhibitor of the steroid biosynthesis
      enzyme delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD), on vestibular
      compensation under conditions of stress. After UL, Wistar rats were divided into
      five groups as follows and subjected to stress and/or drug application: UL only
      (native, n = 6); UL + stress (S, n = 6); UL + vehicle (V, n = 5); UL + stress +
      vehicle (S + V, n = 5); and UL + stress + TRIL (S + TRIL, n = 5). In the S group,
      the decrease in frequency of spontaneous nystagmus (SN) was significantly (p <
      0.05) slower than, in the native group at 3, 12, 24, 30, 36 and 48 h. The
      decreases in frequency of SN in the V and S + V groups were similar to those in
      the native and S groups, respectively, suggesting that neither handling on
      injection nor administration of vehicle affected vestibular compensation. In the
      S + TRIL group, the frequency of SN was significantly (p < 0.05) less than that m
      the S + V group at 24 h after UL. At 30 h, the frequency of SN m the S + TRIL
      group was almost the same as that in the V group. These findings suggest that
      stress attenuates vestibular compensation and that changes in steroid
      concentrations account at least in part for this attenuation.

PMID- 10958403
TI  - Balance control near the limit of stability in various sensory conditions in
      healthy subjects and patients suffering from vertigo or balance disorders: impact
      of sensory input on balance control.
AB  - The large inter-individual variability within the normal population, the limited
      reproducibility due to habituation or fatigue, and the impact of instruction and
      the subject's motivation, all constitute a major problem in posturography. These
      aspects hinder reliable evaluation of the changes in balance control in the case
      of disease and complicate objectivation of the impact of therapy and sensory
      input on balance control. In this study, we examine whether measurement of
      balance control near individualized limits of stability and under very
      challenging sensory conditions might reduce inter- and intra-individual
      variability compared to the well-known Sensory Organization Test (SOT). To do so,
      subjects balance on a platform on which instability increases automatically until
      body orientation or body sway velocity surpasses a safety limit. The maximum
      tolerated platform instability is then used as a measure for balance control
      under 10 different sensory conditions. Ninety-seven healthy subjects and 107
      patients suffering from chronic dizziness (whiplash syndrome (n = 25), Meniere's
      disease (n = 28), acute (n = 28) or gradual (n = 26) peripheral function loss)
      were tested. In both healthy subjects and patients this approach resulted in a
      low intra-individual variability (< 14.5(%). In healthy subjects and patients,
      balance control was maximally affected by closure of the eyes and by vibration of
      the Achilles' tendons. The other perturbation techniques applied (sway referenced
      vision or platform, cooling of the foot soles) were less effective. Combining
      perturbation techniques reduced balance control even more, but the effect was
      less than the linear summation of the effect induced by the techniques applied
      separately. The group averages of healthy subjects show that vision contributed
      maximum 37%, propriocepsis minimum 26%, and labyrinths maximum 44% to balance
      control in healthy subjects. However, a large inter-individual variability was
      observed. Balance control of each patient group was less than in healthy subjects
      in all sensory conditions. Similar to healthy subjects, patients also show a
      large inter-individual variability, which results in a low sensitivity of the
      test. With the exception of some minor differences between Whiplash and Meniere
      patients, balance control did not differ between the four patient groups. This
      points to a low specificity of the test. Balance control was not correlated with
      the outcome of the standard vestibular examination. This study strengthens our
      notion that the contribution of the sensory inputs to balance control differs
      considerably per individual and may simply be due to differences in the
      vestibular function related to the specific pathology, but also to differences in
      motor learning strategies in relation to daily life requirements. It is difficult
      to provide clinically relevant normative data. We conclude that, like the SOT,
      the current test is merely a functional test of balance with limited diagnostic
      value.

PMID- 10958404
TI  - Middle fossa approach in vestibular schwannoma surgery. Postoperative hearing
      preservation and EEG changes.
AB  - When the middle fossa (MF) approach was introduced in Denmark, we were concerned
      about the possible risk to the temporal lobe caused by the retraction of the lobe
      when exposing the internal acoustic meatus. EEG recordings were therefore
      obtained prospectively before (21 patients) and after MF tumor removal (all 23
      patients operated from 1989 to 1997). Only three patients had normal EEG
      recordings before and after surgery, while 86% had induction, or worsening, of
      focal and paroxystic activity, even at the last follow-up (median 3.5 years).
      Sixteen patients operated prospectively via the translabyrinthine (TL) also had
      pre- and postoperative EEG and served as a control group. Only minor EEG changes
      were found in this group. In neither group did the patients display any clinical
      neurological signs (seizures). At the latest evaluation the facial function was
      reduced in 8 patients (35%) with 6 patients going 1 step up the scale, 1 patient
      2 steps up and 1 patient 3 steps up (from HB-1 to HB-4). The integrity of the
      facial nerve was maintained in all patients. Postoperatively, 10 patients (44%)
      had useful hearing (hearing class A and B) on the operated side. Four patients
      had anacusis and an additional 4 patients were reduced to hearing class D with
      very low PTA and SDS. In total, 9 patients (39%) retained their preoperative
      hearing class, while 14 patients (61%) had impairment in their hearing class. In
      conclusion, EEG changes (low frequency activity and IEA) may be provoked or
      worsened as part of the middle cranial fossa procedure. The mechanism is not
      fully known, but may reflect peroperative pressure on the temporal lobe. EEG
      changes are fewer and lighter in translabyrinthine-operated patients. The
      practical clinical implications of the possibility of developing EEG changes,
      even without clinical signs, are potentially serious, and must be included in the
      information given to the patients before surgery.

PMID- 10958405
TI  - Effects of alcohol on the acoustic reflex threshold in the chinchilla.
AB  - The effect of ethanol on the acoustic reflex threshold was examined in a repeated
      measure design study in six chinchillas. Each subject was weighed and orally
      administered the control (water) at a dosage of 7.5 ml/kg. Commencing 1 h after
      alcohol ingestion, the acoustic middle ear reflex measures (AMRs) were taken
      every other hour, for a total of four recording sessions. Ascending and
      descending trials were alternated between each recording session. Two weeks later
      the same chinchillas were administered 35% alcohol by volume. AMRs were recorded
      under the same conditions and procedures as for the control. Alcohol produced
      AMRs that were significantly elevated over baseline values 1 h after alcohol
      ingestion and four of the five had AMRs that remained elevated 3 h after
      ingestion.

PMID- 10958406
TI  - Temporal code and speech recognition.
AB  - The hypothesis that temporal code is mainly responsible for speech recognition is
      discussed. Data from cochlear implant research demonstrate that single-channel
      speech processors, supplying only temporal code, enable understanding of spoken
      language. Physiological findings supporting the observation are presented. A
      temporal theory of tone pitch perception is discussed.

PMID- 10958407
TI  - Arachidonic acid metabolites in antrochoanal polyp and nasal polyp associated
      with chronic paranasal sinusitis.
AB  - The aim of this study was to investigate the role of arachidonic acid metabolites
      (AAMs) in the pathogenesis of antrochoanal polyp (ACP). Using high-performance
      liquid chromatography (HPLC), we assayed the tissue concentrations of 6-keto
      PGF1alpha, leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETE).
      Concentrations of AAMs in ACP were compared with the level in the control
      turbinate tissues and nasal polyps associated with chronic paranasal sinusitis
      (NPS). The concentrations of 6-keto-PGF1alpha were not significantly different in
      the control turbinate, ACP and NPS groups. In ACP, concentrations of LTC4, 15
      HETE and 12-HETE were significantly lower than in the control turbinate. The
      striking differences in the profile of AAMs between ACP and NPS included a lack
      of production of LTD4 and LTE4 in ACP, also detectable in NPS, and markedly lower
      concentrations of 15-HETE and 12-HETE in ACP. The results of this study indicate
      that decreased lipoxygenase pathway products in arachidonic acid metabolism may
      be involved in the pathogenesis of ACP. However, in the pathogenesis of NPS,
      increased production of LTD4 and LTE4 may have an important role. Taken together,
      our results demonstrate a difference in pathogenesis between ACP and NPS,
      particularly in terms of arachidonic acid metabolism.

PMID- 10958408
TI  - Uptake of BrdU in olfactory and respiratory epithelium of rabbits with
      experimental sinusitis.
AB  - Sinusitis was induced in six rabbits in order to evaluate its influence on the
      proliferation of cells in the olfactory epithelium compared with the respiratory
      epithelium during conservative antibiotic therapy. Then 1% ofloxacin was injected
      into the paranasal sinuses. Three normal rabbits were not administered any
      treatment and served as controls. The rabbits were sacrificed under intravenous
      anesthesia and the olfactory and respiratory mucosa was excised 24 hours after
      intravenous administration with the labeling reagent 5-bromo-2'-deoxyuridine
      (BrdU). The extent of cell proliferation in these tissues was estimated by
      immunohistochemical staining with BrdU-specific antibody. The uptake of BrdU was
      significantly increased (p = 0.0099) in the respiratory mucosa, but not in the
      olfactory mucosa. Furthermore, in olfactory epithelium, 79.2% and 16.7% of all
      BrdU-positive cells were olfactory and basal, respectively. Thus, turnover of
      epithelial cells due to sinusitis was not as accelerated in the olfactory mucosa
      as in the respiratory mucosa during antibiotic treatment.

PMID- 10958409
TI  - Detection of human papillomavirus in laryngeal squamous dysplasia and carcinoma.
      An in situ hybridization and signal amplification study.
AB  - We examined the presence of human papillomavirus (HPV) DNA in 65 cases of
      laryngeal squamous dysplasia and carcinomas using in situ hybridization with
      signal amplification in paraffin sections. Hybridization was performed with
      biotinylated DNA probes for HPV 6/11, 16/18, 31/33 and wide-spectrum HPV (6, 11,
      16, 30, 31, 45, 51 and 52). HPV DNA was found in 7 cases of the total sample
      (10.7%); it was also found in 4 out of 45 (8.8%) cases of invasive carcinoma and
      in 5 out of 33 (15.5%) cases of squamous dysplasia. Morphological signs
      suggestive of HPV infection were observed in 35.5% of our sample but they were
      not related to HPV DNA positivity. In conclusion, HPV probably plays little, if
      any, role in laryngeal carcinogenesis among the population studied.

PMID- 10958410
TI  - Primary non-Hodgkin's lymphoma of the nasal cavity. Clinical case report and
      discussion.
AB  - Primary non-Hodgkin's lymphoma of the nasal cavity is a disease more likely to
      affect men than women; it is characterized by a T cell immunophenotype and is
      often associated with involvement of the paranasal structures and with high
      recurrence rates. Many authors report that its extremely poor prognosis depends
      on tumour stage and extension into the paranasal sinuses. Patients with Ann Arbor
      stage IE limited to only one nasal cavity have better survival rates than those
      with the same stage but with tumour extension beyond the nasal cavity. Patients
      with stages IIE, IIIE and IV have a very poor prognosis that does not seem to be
      affected by the use of conventional chemotherapy. Optimal treatment for the
      disease is not yet known. The use of radiotherapy alone has been reported in
      initial stages of the disease; however, given that its prognosis is burdened by
      frequent local or systemic recurrence or both, combined modality therapy has been
      applied in all stages. In this case report we describe a case of primary non
      Hodgkin's lymphoma of the nasal cavity localized at the middle turbinate, in
      combination with an updated literature review.

PMID- 10958411
TI  - Histological rearrangement in the facial nerve and central nuclei following
      immediate and delayed hypoglossal-facial nerve anastomosis.
AB  - The timing of hypoglossal-facial nerve anastomosis is controversial. The present
      study was performed to clarify the influence of the timing of hypoglossal-facial
      nerve anastomosis on histological changes in the facial nerve and central nuclei
      using guinea pigs. The facial nerve was transected first at the labyrinthine
      portion, and then transected again at the stylomastoid foramen. Hypoglossal
      facial nerve anastomosis was carried out immediately or 3 months later. Nerve
      regeneration and survival of the neurons in the facial and hypoglossal nuclei
      were evaluated by toluidine blue staining and horseradish peroxidase (HRP).
      Immediate anastomosis resulted in better nerve regeneration of the facial nerve,
      but the numbers of surviving neurons in the facial and hypoglossal nuclei were
      almost the same in both the immediate and delayed anastomosis groups.

PMID- 10958412
TI  - Significance of Fas protein in squamous cell carcinoma of the larynx.
AB  - The purpose was to elucidate the clinical significance of Fas protein in
      laryngeal squamous cell carcinoma (LSSC). Medical records of 30 patients who were
      operated for LSCC between 1991 and 1997 were reviewed, and histopathological and
      immunohistochemical studies of the archival tumor tissues were performed.
      Conventional histopathology included tumor grading, mitotic counting (MC) and
      status of the cervical lymph nodes. The monoclonal antibodies to Fas (DAKO M
      3554) and nm23 (DAKO A0096 Lot 035) proteins were used for immunohistochemical
      staining. Streptavidin-Biotin, horseradish method was used. Positive staining for
      both Fas and nm23 was obtained in 27 (90%) tumor samples. There was no
      correlation between neck metastasis and Fas positivity (r = 0.126, p = 0.505 and
      chi2 = 0.062, p = 0.996, respectively). Fas positivity did not correlate to grade
      (r = 0.282, p = 0.130), tumor size or T (r = 0.0457, p = 0.810, chi2 = 0.0.018, p
      = 0.999) or laryngeal site of involvement (chi2 = 0.0937, p = 0.992). However, a
      correlation was found between Fas and MC (r = 0.482. p = 0.007). There was also a
      correlation between Fas and nm23 positivity (r = 0.614, p < 0.0001). Fas protein
      expression has no prognostic value in LSCC, because the Fas values do not
      correlate with grade, stage or nodal status of neck. However, 90% of LSCCs
      expressed Fas protein. Understanding the functional status of the Fas receptor
      proteins may lead to development of new therapeutic options for LSSC in the
      future.

PMID- 10958413
TI  - Life and death near a windy oasis.
AB  - We propose a simple experiment to study delocalization and extinction in
      inhomogeneous biological systems. The nonlinear steady state for, say, a bacteria
      colony living on and near a patch of nutrient or favorable illumination ("oasis")
      in the presence of a drift term ("wind") is computed. The bacteria, described by
      a simple generalization of the Fisher equation, diffuse, divide A --> A + A, die
      A --> 0, and annihilate A + A --> 0. At high wind velocities all bacteria are
      blown into an unfavorable region ("desert"), and the colony dies out. At low
      velocity a steady state concentration survives near the oasis. In between these
      two regimes there is a critical velocity at which bacteria first survive. If the
      "desert" supports a small nonzero population, this extinction transition is
      replaced by a delocalization transition with increasing velocity. Predictions for
      the behavior as a function of wind velocity are made for one and two dimensions.

PMID- 10958414
TI  - Uniform persistence for sigmoidal diet selection with keystone prey species.
AB  - In this paper we discuss uniform persistence (UP) criteria of two prey- one
      predator systems, where we consider that the predator's diet selection is a
      sigmoidal function of the most profitable prey type in place of a step function
      of conventional diet choice theory. We also derive UP results of the system with
      direct interspecific competition between the prey. The role of the most
      profitable prey item as a keystone species, the magnitude of its carrying
      capacity, the ability to withstand predation of both prey species, and the ratios
      of their profitability values (to predators) are important to whether or not
      adaptive foraging may promote UP. In general, foraging decision rules play no
      role in UP if the alternative prey item is the keystone species. The result is
      also not affected by the effect of direct competitive coexistence or dominance
      relationship of the prey. In some cases, dominance of one of the prey species
      provides the most advantageous situation for ensuring UP.

PMID- 10958415
TI  - Stability of the human respiratory control system. I. Analysis of a two
      dimensional delay state-space model.
AB  - A number of mathematical models of the human respiratory control system have been
      developed since 1940 to study a wide range of features of this complex system.
      Among them, periodic breathing (including Cheyne-Stokes respiration and apneustic
      breathing) is a collection of regular but involuntary breathing patterns that
      have important medical implications. The hypothesis that periodic breathing is
      the result of delay in the feedback signals to the respiratory control system has
      been studied since the work of Grodins et al. in the early 1950's [12]. The
      purpose of this paper is to study the stability characteristics of a feedback
      control system of five differential equations with delays in both the state and
      control variables presented by Khoo et al. [17] in 1991 for modeling human
      respiration. The paper is divided in two parts. Part I studies a simplified
      mathematical model of two nonlinear state equations modeling arterial partial
      pressures of O2 and CO2 and a peripheral controller. Analysis was done on this
      model to illuminate the effect of delay on the stability. It shows that delay
      dependent stability is affected by the controller gain, compartmental volumes and
      the manner in which changes in the ventilation rate is produced (i.e., by deeper
      breathing or faster breathing). In addition, numerical simulations were performed
      to validate analytical results. Part II extends the model in Part I to include
      both peripheral and central controllers. This, however, necessitates the
      introduction of a third state equation modeling CO2 levels in the brain. In
      addition to analytical studies on delay dependent stability, it shows that the
      decreased cardiac output (and hence increased delay) resulting from the
      congestive heart condition can induce instability at certain control gain levels.
      These analytical results were also confirmed by numerical simulations.

PMID- 10958416
TI  - Stability of the human respiratory control system. II. Analysis of a three
      dimensional delay state-space model.
AB  - A number of mathematical models of the human respiratory control system have been
      developed since 1940 to study a wide range of features of this complex system.
      Among them, periodic breathing (including Cheyne-Stokes respiration and apneustic
      breathing) is a collection of regular but involuntary breathing patterns that
      have important medical implications. The hypothesis that periodic breathing is
      the result of delay in the feedback signals to the respiratory control system has
      been studied since the work of Grodins et al. in the early 1950's [1]. The
      purpose of this paper is to study the stability characteristics of a feedback
      control system of five differential equations with delays in both the state and
      control variables presented by Khoo et al. [4] in 1991 for modeling human
      respiration. The paper is divided in two parts. Part I studies a simplified
      mathematical model of two nonlinear state equations modeling arterial partial
      pressures of O2 and CO2 and a peripheral controller. Analysis was done on this
      model to illuminate the effect of delay on the stability. It shows that delay
      dependent stability is affected by the controller gain, compartmental volumes and
      the manner in which changes in the ventilation rate is produced (i.e., by deeper
      breathing or faster breathing). In addition, numerical simulations were performed
      to validate analytical results. Part II extends the model in Part I to include
      both peripheral and central controllers. This, however, necessitates the
      introduction of a third state equation modeling CO2 levels in the brain. In
      addition to analytical studies on delay dependent stability, it shows that the
      decreased cardiac output (and hence increased delay) resulting from the
      congestive heart condition can induce instability at certain control gain levels.
      These analytical results were also confirmed by numerical simulations.

PMID- 10958417
TI  - The free revascularized lateral upper arm flap in maxillofacial reconstruction
      following ablative tumour surgery.
AB  - The lateral arm flap is well established in microvascular reconstructive surgery
      for covering small and moderate-sized defects both of the extremities and in the
      head and neck region. In the last 3 years 25 patients underwent a lateral upper
      arm flap for primary repair of tumour related defects of the tongue (n = 10),
      floor of the mouth (n = 7), mandible (n = 4), inner cheek (n = 2), oropharynx (n
      = 1) and lower lip (n = 1). Defects extended from the anterior floor of the mouth
      to the oral tongue in three cases and in four cases the defect reached the
      pharyngeal tongue. Two flaps had neurovascular anastomoses between the posterior
      cutaneous nerve of the arm and the lingual nerve. In all patients the donor
      defect was closed primarily. Twenty four lateral upper arm flaps healed
      uneventfully although six patients developed severe alcoholic delirium. One flap
      was lost on the fourth postoperative day due to venous insufficiency. There were
      no significant complications at the donor site. At the time of this report 16
      patients were taking a normal diet while nine patients were taking pureed food.
      Among the advantages of this flap are anatomically reliable vascular supply, its
      good aesthetic quality, and position of the donor site. Furthermore the posterior
      radial collateral artery is a nonessential vessel of the arm. The flap is also
      potentially sensate. Among the disadvantages are smaller vessels for
      microvascular anastomoses. In conclusion, we believe that for repair of moderate
      sized defects of the maxillofacial area the lateral upper arm flap can be
      recommended as the first choice.

PMID- 10958418
TI  - Comparative study on sensory recovery after oral cavity reconstruction by free
      flaps: preliminary results.
AB  - Anatomical restoration was once the only goal of reconstructive surgery, but now
      it represents only one step in the complete functional recovery process to allow
      resumption of physiological activity. Soft tissue and nerves play important roles
      in functional recovery, but the potential of these structures is not yet well
      known. Rehabilitation after oral cavity reconstruction by free flaps needs an
      interdisciplinary diagnostic and therapeutic approach, in which neurosensory
      recovery of transferred tissue is an important aspect. Previous studies have used
      clinical assessment to evaluate sensory recovery after oral reconstruction with
      free flaps, but these results have been subjective and not quantifiable. The aim
      of the present study is to evaluate the sensory recovery using objective and
      standardized electrophysiological data by recording the masseter inhibitory
      reflexes (MIR) following mental and lingual electrical stimulation. A group of 14
      patients who underwent oral cavity reconstruction by transplantation of either
      forearm (9) or jejunal (5) noninnervated free flaps were investigated. We found
      that sensory recovery of fasciocutaneous radial forearm free flaps was better
      than that of jejunal free flaps. This could represent the starting point for
      further studies about sensory recovery of reconstructed anatomical structures
      based on standardized and objective electrophysiological data.

PMID- 10958419
TI  - The quadrangular osteotomy revisited.
AB  - The results are reported on six patients who underwent a modified quadrangular
      osteotomy to avoid dysaesthesia of the infraorbital nerve. The suggested
      modification served its purpose well, while the functional and aesthetic results
      were excellent.

PMID- 10958420
TI  - The role of a posteriorly inclined condylar neck in condylar resorption after
      orthognathic surgery.
AB  - Recently, it has been reported that a posteriorly inclined condylar neck is
      associated with condylar resorption following orthognathic surgery, although its
      role in resorption remains unknown. By cephalometric screening of 240 patients
      with Angle Class II occlusion 2 years after orthognathic surgery, 11 patients
      with postoperative condylar resorption were identified. The preoperative
      posterior inclination of the condylar neck and the surgical risk factors
      mentioned in the literature, particularly surgically induced counterclockwise
      rotation of the mandibular proximal segment were evaluated. In all 11 cases, the
      condylar neck was clearly inclined posteriorly. Counterclockwise rotation of the
      proximal segment was also observed in all cases, and it amounted to 6.7 degrees
      (2.5-12 degrees) on average. The contributing role of a posteriorly inclined
      condylar neck in connection with surgical mandibular movement in postoperative
      condylar resorption is discussed.

PMID- 10958421
TI  - Experimental and finite element study of a human mandible.
AB  - Knowledge of the complex biomechanical behaviour of the human mandible is of
      great importance in various clinical situations. Various approaches can be used
      to evaluate the physical behaviour of bony specimens. In the course of this
      study, we investigated mandibular deformation under mechanical loads in an
      experimental setting and compared them with results derived from finite element
      analysis (FEA). A special apparatus was developed to apply various forces under
      defined conditions on an explanted human mandible in vitro. Strains on the
      surface of the mandible were measured with strain gauges and subsequently a voxel
      based finite element mesh was generated. Strain patterns of the mandible were
      calculated in the FE analysis and matched with the experimental data. Comparing
      the numerical with the experimental data, we found a good correlation between in
      vitro measurements and mathematical modelling (correlation coefficient = 0.992).
      Then the FE model was used to evaluate mandibular biomechanics relative to
      aspects of load transfer, stress distribution and displacements. It is concluded
      that the applied procedure of generating the FE model is a valid and accurate,
      non-invasive method to predict different parameters of the complex biomechanical
      behaviour of human mandibles.

PMID- 10958422
TI  - Functional reconstruction of the TM joint in cases of severely displaced
      fractures and fracture dislocation.
AB  - In a clinical and axiographic study the outcome of patients with severely
      displaced fractures and fracture dislocations of the mandibular condyle was
      evaluated. Two operation methods were compared one via an intraoral approach
      without joint revision and another via a preauricular approach with open
      reduction of the joint. In the group with joint revision, resorbable material was
      used for osteosynthesis. Twenty-eight patients (32 joints) treated without
      revision of the joint and 26 patients (29 joints) with open reduction of the
      joint were evaluated. The mean observation time following surgery was 3 years and
      10 months (range 1-7.5 years). Clinical examination utilized the Helkimo-index,
      while the electronic axiographical results were evaluated by using a five point
      scheme of joint-mobility. Concerning clinical evaluation, 20 out of 28 patients
      (71%) without joint revision and 23 out of 26 (89%) patients with joint revision
      had none or only slight dysfunction of the stomatognathic system. When focusing
      on arthralgia and pain in motion (part D and E of Helkimo's-index) significantly
      better results were achieved by open joint revision (Helkimo D: p< or =0.007;
      Helkimo E: p = 0.0029). No patient exhibited severe dysfunction (group D3). In
      axiographic evaluation optimal results (group A1) were achieved in seven joints
      (24%) with revision and four joints (12%) without revision. Twelve out of 29
      joints with revision (41%) and six out of 32 joints without revision (19%) were
      classified as group A2 with a slightly shortened condylar excursion. Revision of
      joints with disc reduction and reconstruction of ligaments in cases of severely
      displaced or dislocated fractures resulted in better mobility and less pain. This
      was seen clinically and in the axiographic results. Looking at the long-term
      outcome of patients better mobility of the joint without internal derangement due
      to surgical repair also protects the contralateral (nonoperated) joint. When
      managing severe TMJ-trauma we suggest that both, bony and soft tissue structures
      should be reconstructed if there are any signs of internal derangement. However,
      the limits between bony reconstruction with or without joint revision are still
      not defined. Our results appear to be promising concerning mobility and absence
      of pain of the joints after open reduction. Further research comparing the two
      operative treatment regimes in a randomized controlled clinical trial will be
      necessary.

PMID- 10958423
TI  - Oculocardiac reflex induced by zygomatic fracture; a case report.
AB  - Oculocardiac reflex has been recognized as the result of mechanical stimulation
      to the orbital tissue. The authors encountered a case of severe arrhythmia due to
      oculocardiac reflex in a patient with a zygomatic fracture. Previous health
      examinations suggested no abnormalities in the heart in his schooldays, and the
      initial diagnosis of his arrhythmia as complete A-V block due to injury (using
      ECG and cardiac ultrasonography). Because his arrhythmia did not improve
      spontaneously, he underwent cardiac pacing. After repair of the fracture, his
      arrhythmia completely disappeared. The pacemaker was removed on the first
      postoperative day. The pathogenesis of this rare case will be discussed.

PMID- 10958424
TI  - Comparisons of bone volumes and densities relating to osseointegrated implants in
      microvascularly reconstructed mandibles: a study of cadaveric radius and fibula
      bones.
AB  - The study was designed to compare the dimensions and densities of two frequently
      used bone donor sites with regard to placement of endosseous dental implants in
      microvascularly reconstructed mandibles. A total of 40 radii and of 40 fibulae
      were investigated. Fifty two percent of the fibulae had adequate bone volume for
      the positioning of four 10 mm implants, while this figure was 55% for the radii.
      After using the 'double barrel' technique the placement of four 10 mm implants
      succeeded in 87% of all the fibulae. Due to the lack of bone length required,
      this special technique was not possible in the radii investigated. Cortical
      thickness and density of bone were higher in the radii when compared with the
      fibulae. In each bone the central and distal parts presented the highest values
      of cortical thickness and density. Although the radius offers enough substantial
      bone for implant placement in some cases this cannot be used for clinical
      purpose, as only hemicortical grafts can be obtained. Otherwise the resulting
      donor site morbidity would be intolerable. In conclusion, our results support the
      clinical experience that the fibula is today's 'work horse' donor site for
      reconstruction of the mandible.

PMID- 10958425
TI  - Histological evaluation of different biodegradable and non-biodegradable
      membranes implanted subcutaneously in rats.
AB  - Different types of biodegradable membranes have become available for guided
      tissue regeneration. The purpose of this study was to evaluate histologically
      three different biodegradable membranes (Bio-Gide, Resolut and Vicryl) and one
      non-biodegradable membrane (expanded polytetrafluoroethylene/e-PTFE) implanted
      subcutaneously in rats. Five subcutaneous pouches were created in each of 24
      rats. One of the four test membranes was randomly placed in each of the four
      pouches and one pouch was left empty to serve as a control. Histological
      evaluation was performed after 4, 10 and 21 days which demonstrated that e-PTFE
      was well tolerated and encapsulated by a fibrous connective tissue capsule. There
      was capsule formation around Resolut and Vicryl and around Bio-Gide in the early
      phase there was a wide inflammatory zone already. e-PTFE and Vicryl were stable
      materials while Resolut and Bio-Gide fragmented in the early phase. In the late
      phase Vicryl was surrounded by an increasing amount of multinucleated macrophages
      and a thin capsule, whilst around Resolut and Bio-Gide a strong foreign body
      reaction was observed. Also granuloma formation was noted around the fragmented
      Resolut material in its capsule and a mild inflammatory reaction surrounding Bio
      Gide within its thin capsule.

PMID- 10958426
TI  - The long styloid process syndrome or Eagle's syndrome.
AB  - Eleven cases of Eagle's syndrome or long styloid process syndrome are presented.
      It is a rare entity, which is not commonly suspected in clinical practice.
      Symptoms were dull and persistent pharyngeal pain, dysphagia, and facial pain. In
      addition to careful clinical examination, the use of plain radiographs,
      orthopantomograms or CT scan has allowed accurate preoperative diagnosis of this
      syndrome. Surgical treatment has positively resolved the symptoms in these cases.
      The International literature is discussed regarding anatomy, symptoms and
      treatment of the long styloid process syndrome.

PMID- 10958427
TI  - Preface: assessing children's language: present, past, and future.

PMID- 10958428
TI  - All children are ready to learn: an emergent versus readiness perspective in
      early literacy assessment.
AB  - Assessment of emergent literacy is relatively new to the field of communication
      disorders. Traditional approaches to reading assessment evaluated mastery of
      reading readiness skills. By contrast, emergent literacy assessment evaluates the
      increased awareness and understanding of print that begin early in development.
      One of the most influential figures in emergent literacy assessment has been
      Marie M. Clay. She has defined critical components of emergent literacy and, in
      so doing, has played an integral role in the paradigm shift from a reading
      readiness to an emergent literacy perspective. This article is intended to
      distinguish emergent literacy from reading readiness, explicate Marie Clay's
      contribution to our current understanding of effective emergent literacy
      assessment, and provide some guidance in using her assessment techniques with
      children with significant disabilities.

PMID- 10958429
TI  - Assessing socially situated participation: a way of integrating communication and
      social assessment approaches.
AB  - We have long treated communication and social assessment as related but separate
      domains. Theorizing by George Herbert Mead on "the social self" offers an
      alternative to this conceptual separation and a means of evaluating children's
      social interaction, social participation, and communication simultaneously. This
      article describes Mead's thinking and presents a framework for assessing
      children's social reciprocity, interactive stances, and role participation as
      they participate in everyday life contexts.

PMID- 10958430
TI  - Dynamic assessment: an approach to assessing children's language-learning
      potential.
AB  - Dynamic assessment represents an alternative approach to traditional language
      assessments. In dynamic assessment, the examiner attempts to assess the child's
      potential for language change or modifiability. This article discusses the
      development of this approach from its early psychological applications to current
      models of dynamic assessment as they apply to the assessment of child language.
      Dynamic assessment is particularly useful in addressing cultural differences that
      may influence children's assessment performance. The approach involves a test
      teach-retest paradigm that includes mediated learning experiences, measures of
      test score gains, ratings of modifiability and language-learning strategies, as
      well as analyses of qualitative changes in children's responses.

PMID- 10958432
TI  - Assessing children's vocabulary skills: from word knowledge to word-learning
      potential.
AB  - Knowledge of word meanings and the ability to use words are fundamental to nearly
      every interaction of every day. Beginning long before formal schooling,
      vocabulary skills underpin many aspects of communicative, social, and academic
      well-being. Thus, evaluation of vocabulary knowledge and use is central to any
      complete assessment of language proficiency. We have advanced in our use of
      vocabulary assessment significantly since Binet and Simon first used vocabulary
      tests to measure cognitive proficiency. We have a repertoire of informative tools
      and strategies from which vocabulary assessment protocols can be fashioned.
      Current assessment approaches integrate multiple sources of information. They
      also look beyond existing word knowledge toward word-learning potential.
      Integrated and dynamic approaches can provide a rich way to ascertain young
      children's vocabulary abilities and aptitudes.

PMID- 10958431
TI  - Culturally sensitive assessment of narrative skills in children.
AB  - The clinical legacy of William Labov's narrative analysis framework is explored.
      In recent years, the importance of narration for children's developing literacy
      and discourse skills has been widely recognized. This article describes a three
      step process for assessing children's narrative discourse: elicitation, coding,
      and scoring. The influences of cultural differences on narration are also
      presented, with implications and suggestions for culturally sensitive assessment.

PMID- 10958433
TI  - "Putting things in context": literal and discourse approaches to comprehension
      assessment.
AB  - Research on receptive language development in typical children, especially as
      explicated in a classic paper by Robin Chapman, is reviewed. These findings raise
      three challenges for clinicians assessing comprehension in children with language
      disorders: (1) contrary to popular wisdom, comprehension does not always precede
      production in a simple step-by-step way; (2) comprehension is a private event;
      indicators of comprehension must be used to assess it, and these indicators can
      be misleading; and (3) children with subtle comprehension deficits may do well on
      standardized tests that are not sensitive to their difficulties with real-time
      discourse. Some strategies for addressing these challenges, as well as a
      framework for assessing comprehension, are offered.

PMID- 10958434
TI  - Assessing communicative intents: a situated pragmatics approach.
AB  - The analysis of communicative intents is described as it has developed over time,
      beginning with J.L. Austin's work published in 1975. Recommendations for best
      practice are offered in which a situated approach is advocated. Key elements of
      this approach are a focus on contextual variables and open-ended, rather than
      list-oriented, assessments of range of intents. It is argued that intents must be
      assessed relative to the environment, with documentation of environmental
      variables such as barriers to communicative opportunity. Further, caution is
      urged in using lists of intents as the sole guide to analysis, because such lists
      serve to limit awareness of individual differences and multifunctionality of
      utterances.

PMID- 10958435
TI  - Assessment of language structure: from syntax to event-based analysis.
AB  - The last 70 years have seen much research and clinical attention devoted to the
      descriptions and assessment of children's developing language structures. From
      these efforts have evolved a number of ways to describe the kinds of structures
      children evidence at different stages of development, and thus the means to make
      comparisons across children or across time periods. This article reviews major
      trends that have emerged in syntactic descriptions and approaches to language
      habilitation, culminating in contemporary approaches that view syntactic
      structure in real life events rather than in artificial tasks or with arbitrary
      checklists. These new approaches allow us to determine the communication goals
      that are not being met rather than cataloging the syntactic structures that have
      not yet been mastered and provide us with the contexts for helping the children
      develop structures that will lead to clearer expression of meanings and fewer
      breakdowns in communication.

PMID- 10958436
TI  - Transient nature of Toxoplasma gondii-induced behavioral changes in mice.
AB  - Many parasites induce specific changes in host behavior that promote the
      transmission of their infective stages between hosts. Toxoplasmosis in rodents is
      known to be accompanied by specific behavioral changes (shift in activity level,
      learning capacity, and novelty discrimination) that can theoretically increase
      the chance of infected animals being eaten by the definitive host, the cat.
      However, toxoplasmosis is also accompanied by many pathological symptoms. It is
      not known whether the behavioral changes are products of manipulation activity of
      the parasite or only nonspecific by-products of pathological symptoms of
      toxoplasmosis. Here, we compared the dynamics of development of behavioral and
      pathological changes in Toxoplasma gondii-infected mice. The results showed that
      the maximum reduction of mouse activity corresponded with the peak of
      pathological symptoms, and also that maximum increase of reaction times
      corresponded with the peak of development of tissue cysts in the brains of
      infected mice. Behavioral changes were only transient and disappeared before the
      12th wk postinoculation. The results suggest that the behavioral changes in
      infected mice reported by many authors and observed in our experiments could be
      nonspecific by-products of pathological symptoms of toxoplasmosis rather than
      specific products of manipulation activity by the parasite.

PMID- 10958438
TI  - In vitro cultivation of schizonts of Sarcocystis speeri Dubey and Lindsay, 1999.
AB  - Schizonts of Sarcocystis speeri Dubey and Lindsay, 1999 were cultured in vitro in
      bovine monocyte and equine kidney cell cultures inoculated with infected tissues
      of nude and gamma-interferon knockout mice fed sporocysts from opossums,
      Didelphis albiventris. At least 1 asexual cycle was completed in 3 days. In vitro
      grown merozoites were structurally and antigenically distinct from those of
      Sarcocystis neurona and Sarcocystis falcatula. Culture-derived merozoites of S.
      speeri were not infective to budgerigars (Melopsittacus undulatus).

PMID- 10958437
TI  - Effect of Triaenophorus crassus (Cestoda) infection on behavior and
      susceptibility to predation of the first intermediate host Cyclops strenuus
      (Copepoda).
AB  - Some parasites have been shown to manipulate host behavior so that parasite
      transmission to the next host is enhanced. Infection with Triaenophorus crassus
      Forel (Cestoda) caused alterations in the activity and microhabitat selection of
      the first intermediate host Cyclops strenuus Fischer (Copepoda) in the
      laboratory. Infected copepods made more starts to swim but spent less time
      swimming than uninfected copepods. These changes were independent of the
      intensity of infection. In a water column illuminated from above, infected
      copepods approached the surface, whereas uninfected ones remained close to the
      bottom. In the dark both infected and uninfected copepods stayed near the bottom.
      Finally, infection with T. crassus increased the probability of C. strenuus being
      eaten by the second intermediate host, whitefish (Coregonus lavaretus L. s.l.),
      in the laboratory. In experimental infections, 10-day-old procercoids had
      significantly lower infectivity for whitefish than older (12-, 14-, and 21-day
      old) procercoids. Behavioral changes were detected in infected copepods
      containing procercoids 12 days old or older but not in experiments with 10-day
      old procercoids. These results may indicate that T. crassus changes the behavior
      of the copepod host only after it has become infective to the next host, which is
      consistent with the active manipulation hypothesis.

PMID- 10958439
TI  - Mortality rate of adult ticks due to infection by entomopathogenic nematodes.
AB  - The mortality of Boophilus annulatus, Hyalomma excavatum, Rhipicephalus bursa,
      and Rhipicephalus sanguineus adult ticks was recorded after their exposure in
      petri dishes to 5 entomopathogenic nematode strains. The strains used were DT and
      Mexican of Steinernema carpocapsae, Hb HP88 of Heterorhabditis bacteriophora, and
      IS-3 and IS-5 of Heterorhabditis sp. The most rapid killing rates (LT50 and LT90)
      were observed for B. annulatus ticks (0.8-5.0 days). Most unfed males died 0.3
      2.8 days after the unfed females, whereas even more time (0.8-8.0 days) passed
      before engorged females died. In most bioassays, the IS-3 and IS-5 strains of
      Heterorhabditis sp. nematodes appear to be the most pathogenic for ticks and, in
      most cases, killed ticks several days before the other 3 nematode strains. Unfed
      adult ticks exposed to nematodes died within less time than it takes for adults
      to complete their prefeeding period after molting.

PMID- 10958440
TI  - Experimental investigation of physiological factors that may influence
      microhabitat specificity exhibited by Leptorhynchoides thecatus (Acanthocephala)
      in green sunfish (Lepomis cyanellus).
AB  - Representatives of Leptorhynchoides thecatus (Acanthocephala) inhabit ceca of
      green sunfish but cannot survive in the anterior intestine. The influence of
      elevated cecal protein concentrations, pH, and amounts of lumenal materials on
      the microhabitat specificity of L. thecatus was investigated. An attempt was made
      to alter the distribution of worms in starved fish, in fish of which cecal pH was
      reduced, and in fish of which intestinal protein concentration was elevated.
      Protein concentration and pH showed no effect on worm distribution. Starving
      hosts had no effect on worm number or distribution but resulted in retardation of
      worm growth and development, providing a mechanism by which worms may overwinter
      and by which peak egg production may coincide with abundance of the amphipod
      intermediate host. None of the factors investigated is solely responsible for the
      microhabitat specificity of L. thecatus. It is suggested that helminth site
      specificity is characterized by long histories of adaptation to specific habitats
      with many physiological adaptations being facilitated synergistically.
      Maximization of sexual congress may exert an important selective pressure
      favoring this establishment of microhabitat specificity.

PMID- 10958441
TI  - Potential interactions between the intestinal helminths of the cichlid fish
      Cichlasoma synspilum from southeastern Mexico.
AB  - This study presents and analyzes positional data on 18 helminth species forming
      the intestinal infracommunities of 59 Cichlasoma synspilum from southeastern
      Mexico. Interspecific interactions were found between 4 pairs of host
      specialists: Crassicutis cichlasomae (Digenea) with Neoechinorhynchus golvani
      (Acanthocephala), Spirocamallanus rebecae (Nematoda) with N. golvani, and
      Raillietnema kritscheri (Nematoda) with N. golvani. The interactions were
      expressed as negative correlations, positional shifts, and reductions in realized
      distribution. It is suggested that N. golvani produces unsuitable habitats for C.
      cichlasomae, S. rebecae, and R. kristscheri. All interactions were found among
      phylogenetically unrelated helminth specialists of cichlids.

PMID- 10958442
TI  - Rhopalobdella japonica n. gen., n. sp. (Hirudinea, Piscicolidae) from Dasyatis
      akajei (Chondrichthyes: Dasyatididae) in the northwestern Pacific.
AB  - A new genus and species of piscicolid leech in the Platybdellinae inhabits the
      oral cavity of Dasyatis akajei in the northwestern Pacific Ocean near Tanabe,
      Japan. The genus Rhopalobdella n. gen. is characterized externally by very small
      oral and caudal suckers and a smooth body that is widest just posterior to the
      clitellum. Eyespots and ocelli are lacking. The coelom is spacious with large
      segmental connecting sinuses between dorsal and ventral sinuses. There are 5
      pairs of testisacs, an unusually extensive epididymis, and a very large bursa.
      Conducting tissue is absent. There are 2 pairs of esophageal diverticula and very
      well developed nephridia. Rhopalobdella japonica n. gen. n. sp. is characterized
      by a urosome that tapers strongly to the caudal sucker and by a single gonopore;
      the common oviduct opens into the posterior portion of the bursa. The coelomic
      and excretory systems resemble Aestabdella, but in other respects the genera are
      quite different. This is the first marine leech reported from rays in the
      northwestern Pacific.

PMID- 10958443
TI  - Introduction of potential heartwater vectors and other exotic ticks into Florida
      on imported reptiles.
AB  - Following the discovery of establishment of the African tortoise tick Amblyomma
      marmoreum in Florida, the present study was undertaken to determine the extent of
      introduction of exotic ticks into Florida on imported reptiles. Exotic ticks were
      identified on 29 (91%) of 32 reptile premises in 18 counties of Florida. The
      ticks, found on a variety of imported tortoises, snakes, and monitor lizards,
      belonged to 4 Amblyomma species (A. marmoreum, Amblyomma nuttalli, Amblyomma
      sabanerae, and Amblyomma sparsum) and 4 Aponomma species (Aponomma exornatum,
      Aponomma flavomaculatum, Aponomma latum, and Aponomma varanensis). The most
      commonly encountered ticks were A. latum and A. marmoreum. The identifications of
      A. marmoreum on 8 premises in 7 counties, and of A. sparsum on 1 premises, are of
      great concern because both species are vectors of heartwater, a lethal disease of
      cattle, sheep, goats, and deer.

PMID- 10958444
TI  - Prevalence of sarcocystis species sporocysts in wild-caught opossums (Didelphis
      virginiana).
AB  - Sarcocystis sporocysts were found in intestinal scrapings from 24 (54.5%) of 44
      opossums (Didelphis virginiana). The number of sporocysts varied from a few (<
      10,000) to 245 million. Sporocysts from 23 of 24 opossums were fed to captive
      budgerigars (Melopsittacus undulatas), and the inocula from 21 opossums were
      infective, indicating the presence of Sarcocystis falcatula. Sporocysts from 24
      opossums were fed to gamma-interferon-knockout (KO) or nude mice; inocula from 14
      opossums were infective to mice. Sarcocystis neurona was detected in tissues of
      KO mice by specific staining with anti-S. neurona antibodies, and the parasite
      was cultured in vitro from the brains of KO mice fed sporocysts from 8 opossums.
      Sarcocystis speeri was identified by specific staining with anti-S. speeri
      antibodies in tissues of KO mice fed inocula from 8 opossums; 3 opossums had
      mixed S. neurona and S. speeri infections. Thus, the prevalences of sporocysts of
      different species of Sarcocystis in opossums were: S. falcatula 21 of 44 (47.7%),
      S. neurona 8 of 44 (18.1%), and S. speeri 8 of 44 (18.1%) opossums. Sarcocystis
      neurona alone was found in 1 opossum, and S. speeri alone was found in 1 opossum.
      Mixed Sarcocystis infections were present in 21 opossums.

PMID- 10958445
TI  - Immunofluorescent localization of intermediate filaments (IFs) in helminths using
      anti-mammalian IFs monoclonal antibody.
AB  - Intermediate filaments (IFs) make up the cytoskeleton of most eukaryotic cells.
      In vertebrates, a number of IF proteins have been identified, showing
      distributions unique to tissue or cell type. Information on helminth IFs is
      limited to some nematode species. To observe immunofluorescent localization of
      IFs in helminth tissues, we selected a murine hybridoma clone producing IgM
      antibody to multiple types of mammalian IF proteins and examined cross-reactivity
      to helminth proteins. The selected monoclonal antibody (HUSM-9) cross-reacted
      well with IFs from nematode species such as Toxocara canis, Dirofilaria immitis,
      Anisakis simplex, and Trichinella britovi; strong immunofluorescence on cryostat
      sections was detected in the hypodermis, cords, body muscle, smooth muscle of the
      uterus, and other epithelial structures. In platyhelminths, i.e., adult
      Schistosoma mansoni, larval Taenia taeniaeformis, adult Taenia crassiceps, and
      Echinococcus multilocularis protoscolex, the reactivity was weaker than in
      nematodes, and localized in the body wall muscle and subtegumental tissue.
      Western blotting of 8 M urea extracts of parasites with the antibody detected a
      pair of clear bands in nematodes but not in S. mansoni or the cestodes. These
      results might be explained by sparse distribution of IFs in platyhelminths, or
      low affinity of the used antibody to platyhelminth IF proteins, or both.

PMID- 10958447
TI  - Morphological comparisons and hypotheses on the origin of polyploids in
      parthenogenetic Fasciola sp.
AB  - It is known that Fasciola sp. from Japan and the Republic of Korea consist of
      diploids (2n = 2x = 20), triploids (2n = 3x = 30), and mixoploids with diploid
      and triploid cells. Triploids are distributed over Asia and Hawaii. Abnormal
      spermatogenesis and parthenogenetic reproduction are the main characteristics of
      Fasciola sp. Here we measured 21 different morphological parameters of diploid
      and triploid flukes of Fasciola sp. obtained from Japan and the Republic of
      Korea. Statistical analysis showed that diploid and triploid flukes were
      morphologically different. No bivalents or trivalents could be detected in
      diploid and triploid flukes, respectively. Based on our findings, we speculate
      that parthenogenetic diploids, triploids, and mixoploids (2x/3x) of Fasciola sp.
      are genetically related to each other.

PMID- 10958446
TI  - Intergenic spacer (IGS) polymorphism: a new genetic marker for differentiation of
      Toxoplasma gondii strains and Neospora caninum.
AB  - The region between the 28S and 18S rRNA genes, including the intergenic spacer
      (IGS) region and the 5S rRNA gene, from 32 strains of Toxoplasma gondii and the
      NC1 strain of Neospora caninum was amplified and used for DNA sequencing and/or
      restriction fragment length polymorphism (RFLP) analysis. The 5S rDNA sequences
      from 20 strains of T. gondii were identical. The IGS region between the 5S and
      18S rRNA genes (nontranscribed spacer 2 or NTS 2) showed 10 nucleotide
      variations. Six of the 10 variant positions correlated with the murine virulence
      of the strains. Intraspecific polymorphisms distinguished the virulent strains of
      zymodemes 5, 6, and 8 from other virulent strains (in zymodeme 1). RFLP methods
      (IGS-RFLP) were developed and used to characterize the virulent and avirulent
      patterns among 29 T. gondii strains. Sequence diversity of 19.8% was found
      between T. gondii and N. caninum when comparing a region of 919 bp at the 3' end
      of NTS 2. The sequence variation in ribosomal IGS could therefore be a useful
      marker for Toxoplasma strain identification and for distinguishing N. caninum
      from T. gondii.

PMID- 10958448
TI  - Induction of partial protection against Leishmania donovani by promastigote
      antigens in negatively charged liposomes.
AB  - Negatively charged liposomes, proposed as potential vaccine adjuvants, have been
      extensively studied in association with various antigens. In the present study,
      we investigated the adjuvanicity of negatively charged liposomes to enhance the
      protective immunity of membrane antigens of Leishmania donovani promastigotes
      (LAg). In comparison to the control mice immunized with phosphate-buffered saline
      and empty liposomes, immunization with free LAg led to significant levels of
      protection against infection with virulent promastigotes. Encapsulation of LAg in
      liposomes also induced effective protection. However, the level of protection by
      LAg-liposome was not significantly different from that induced by free LAg.
      Investigation of the immune responses showed, in contrast to free LAg, that
      immunization with LAg-liposome elicited strong antibody responses. IgG isotype
      analysis revealed the presence of all 4 isotypes. However, the titer of IgG1 was
      significantly higher than IgG2a, IgG2b, and IgG3. Following infection,
      stimulation of IgG and IgG isotypes did not differ in the different immunization
      groups. Delayed-type hypersensitivity (DTH) analysis after immunization showed
      significant induction by LAg and LAg-liposomes, in comparison to controls. With
      infection, again, the level of DTH in all the groups became almost comparable.
      Stimulation of insufficient cellular response, as reflected by DTH and
      potentiation of IgG1 over IgG2a, IgG2b, and IgG3 suggest a dominance of Th2
      response with this liposome-antigen formulation, resulting in weak protection
      against visceral leishmaniasis.

PMID- 10958449
TI  - Role of T cells and cytokines in fatal and resolving experimental babesiosis:
      protection in TNFRp55-/- mice infected with the human Babesia WA1 parasite.
AB  - We characterized the cytokine response and T-cell requirements of mice infected
      with the intraerythrocytic parasites Babesia microti and WA1. WA1 infections were
      fatal, whereas B. microti infections were resolved. We measured production of
      tumor necrosis factor (TNF)-alpha, interferon-gamma, interleukin (IL)-10, and IL
      4 by splenic CD4+, CD8+, and gammadelta+ T cells using flow cytometry. WA1
      inoculation stimulated TNF-alpha production, whereas resolving B. microti
      infections were characterized by increased IL-10 and IL-4. The role of TNF-alpha
      in WA1 infections was further investigated by inoculating TNFRp55-/- mice with a
      lethal dose of WA1. A survival rate of 90% in the TNFRp55-/- mice indicated that
      a disruption in the TNF-alpha pathway abrogated the pathologic mechanism of WA1.
      Inoculation of WA1 into CD4-/- and CD8-/- mice resulted in survival rates of 60%
      and 78%, respectively, whereas WA1 infection in gammadelta-/- and control mice
      was fatal. These results suggest that CD8+ T cells may contribute to the WA1
      associated disease. Babesia-infected CD4-/- mice experienced a longer duration of
      parasitemia, indicating that CD4+ T cells participate in parasite elimination.
      These studies demonstrate differences in immune responses during fatal or
      resolving Babesia infections, and they identify TNF-alpha as an important
      mediator of the WA1-associated pathogenesis.

PMID- 10958450
TI  - Emergence of third-stage larvae of Umingmakstrongylus pallikuukensis from three
      gastropod intermediate host species.
AB  - We investigated the emergence of third-stage larvae (L3) of Umingmakstrongylus
      pallikuukensis from the slugs Deroceras laeve, Deroceras reticulatum, and the
      snail Catinella sp. in the laboratory and from D. laeve on the tundra. Third
      stage larvae emerged from 8 of 8 D. laeve and 8 of 8 D. reticulatum housed at 20
      C in darkness and from 9 of 10 D. laeve and 5 of 5 Catinella sp. housed at 21 C
      with 10-12 hr of light/day. Larvae emerged from D. laeve and D. reticulatum over
      a wide range of infection intensities (2-179 and 20-65, respectively), and the
      patterns of emergence were independent of intensity. The majority of the L3
      emerged from most of the Deroceras spp. by 58 or 60 days postinfection (PI).
      Lower rates of emergence were observed from Catinella sp. Larvae emerged from D.
      laeve on the tundra by 10 wk PI and were recovered from the vegetation in some
      experimental enclosures the following year. Third-stage larvae survived in tap
      and distilled water at 0-4 C for 13 mo. Emergence of L3 of U. pallikuukensis from
      the intermediate host may increase the temporal and spatial availability of L3
      and enhance their survival and transmission.

PMID- 10958451
TI  - Transport of helminths to Hawaii via the brown anole, Anolis sagrei
      (Polychrotidae).
AB  - Sixty-two brown anoles, Anolis sagrei, from Oahu, Hawaii were examined for
      helminths. Anolis sagrei was introduced to Hawaii, presumably from the Caribbean.
      Two species of trematodes, Mesocoelium monas and Platynosomum fastosum, 3 species
      of nematodes, Atractis scelopori, Physaloptera squamatae, and Physocephalus sp.,
      1 acanthocephalan, Acanthocephalus bufonis, and 1 pentastome,
      Raillietiellafrenatus, were found. Atractis scelopori and P. squamatae,
      previously unknown in Hawaii, are widely distributed in the Caribbean and were
      most likely transported to Hawaii with the introduced anoles. Mesocoelium monas,
      P. fastosum, Physocephalus sp., A. bufonis, and R. frenatus have been previously
      reported from Hawaiian herptiles; A. sagrei most likely acquired infections of
      these parasites from Hawaiian populations. This study indicates that helminths
      can be transported with their introduced hosts and become established in the
      colonized areas and that introduced lizards may quickly acquire species of
      previously established helminthes.

PMID- 10958452
TI  - Prevalence and biodiversity of helminth parasites in donkeys from South Africa.
AB  - Seven donkeys (Equus asinus) from North-West and Mpumalanga Provinces in South
      Africa were examined at necropsy. Quantitative samples were collected from the
      gastrointestinal tract for recovery of helminth parasites from the stomach, small
      intestine, cecum, ventral colon, dorsal colon, descending colon, and cranial
      mesenteric artery. Fifteen genera and 29 species of helminths were identified
      comprising 27 species of nematodes in the Ascarididae, Atractidae,
      Habronematidae, Onchocercidae, Oxyuridae, and Strongylidae; 1 species of cestode
      in the Anoplocephalidae; and 1 species of trematode in the Paramphistomatidae. In
      addition, 2 species of oestrid fly larvae in the Gastrophiliidae were identified.
      The most abundant group in number of species was the cyathostomes (small
      strongyles) and, of these, Cyathostomum montgomeryi, Cylicocyclus sp. (a), and
      Cylicostephanus minutus were the most numerous. The most prevalent cyathostomes
      were C. montgomeryi and Cylicocyclus sp. n. (a). Strongylus vulgaris was the most
      abundant and prevalent large strongyle species. The occurrence of small strongyle
      species and their prevalences in this study are compared with 3 other studies on
      donkeys in Africa.

PMID- 10958454
TI  - Progenesis in Proctoeces lintoni (Fellodistomidae), a parasite of Fissurella
      crassa (Archaeogastropoda) in a latitudinal gradient in the Pacific Coast of
      South America.
AB  - The fellodistomid Proctoeces lintoni is a common parasite of the gonads of key
      hole limpets Fissurella spp. (Archaeogastropoda). It has also been found in the
      mantle of Octopus vulgaris and as an intestinal parasite of haemulid and
      gobiesocid fishes. Fissurella crassa, a host for progenetic P. lintoni, can be
      found from Huarmey, Peni (10 degrees S) to Chiloe, Chile (42 degrees S).
      Proctoeces lintoni has been found parasitizing fishes and molluscs from Callao,
      Peni (12 degrees S) to Valdivia, Chile (39 degrees S). Progenesis is thought to
      be a latitude-dependent phenomenon, and high progenesis is expected at higher
      latitude. In the present article, the association between latitude and progenesis
      was examined over a latitudinal gradient of about 3,000 km. Data suggest that
      progenesis of P. lintoni infecting F. crassa was not associated with latitude.
      Low levels of progenesis found in the Peruvian population could be a consequence
      of parasite-induced mortality rather than of low latitude, as would be predicted
      by the latitude dependence hypothesis.

PMID- 10958453
TI  - Experimental trichinellosis in reindeer.
AB  - Six female reindeer calves were inoculated intraruminally with various doses of
      Trichinella muscle larvae. Four calves were inoculated with T. nativa, receiving
      15,000 (n = 1), 5,000 (1), and 2,500 (2) larvae each. Two calves were inoculated
      with 5,000 T. spiralis larvae each. Blood samples were collected twice per week
      for total white blood cell (WBC) and differential counts and for serology using
      enzyme-linked immunosorbent assay (ELISA) based on T. spiralis excretory
      secretory antigen. On day 56, the calves were slaughtered and muscle samples were
      examined according to the standard digestion method for Trichinella larvae. Blood
      samples were also collected twice a week from 4 uninoculated, but otherwise
      similar, reindeer calves corralled separately. Both the total WBC and eosinophil
      counts of the inoculated animals were, on average, higher during the experimental
      period. All the inoculated calves seroconverted, showing an increase in the
      optical density (OD) in the ELISA starting between day 23 and day 27
      postinoculation. Very few muscle larvae (<0.08 larvae/g [lpg]) were to be found
      from the animals inoculated with T. nativa, but about 4 and 6 lpg were recovered
      from the masseter muscles of those inoculated with T. spiralis.

PMID- 10958455
TI  - Life cycle and identification of an eyefluke from Israel transmitted by
      Melanoides tuberculata (Muller, 1774).
AB  - A philophthalmid species from Israel using the freshwater snail Melanoides
      tuberculata as intermediate host was studied. The biological and morphological
      characteristics of all developmental stages of the life cycle of this
      philophthalmid were described, and compared to those of Philophthalmus lucipetus
      Rudolphi, 1819 from Israel, Philophthalmus gralli Mathis and Leger, 1910 from
      Jordan, Philophthalmus palpebrarum Looss, 1899, Philophthalmus nocturnus Looss,
      1907, Cercaria distomatosa Looss 1896 from Egypt, and Philophthalmus lucknowensis
      Baugh, 1962 from India. The possible identity with 1 of these species is
      discussed. On the basis of comparative analysis of the data for all parasite
      stages in the life cycle, geographical distribution, snail hosts, and snail host
      specificity, we propose to designate the Israeli Melanoides tuberculata
      transmitted eye fluke to Philophthalmus distomatosa n. comb. (Looss, 1896),
      (Digenea: Philophthalmidae).

PMID- 10958456
TI  - The initiation translation factor eIF-4A of Cryptosporidium parvum is encoded by
      two distinct mRNA forms and shows DNA sequence polymorphism distinguishing
      genotype 1 and 2 isolates.
AB  - The eukaryotic translation initiation factor eIF-4A is an ATP-dependent RNA
      helicase involved in ribosome attachment to the 5' end of mRNAs. Employing as a
      probe a Cryptosporidium parvum genomic amplicon encoding a partial polypeptide
      related to eIF-4A, we screened a C. parvum sporozoite cDNA library to clone the
      full length of the gene. Two complete cDNAs were characterized, Cp.F6 and Cp.F10,
      which consisted of 1,900 and 1,418 bp, respectively. The overlapping portions of
      the sequences shared 100% identity and encoded a polypeptide of 405 amino acids
      whose identity to known eIF-4A molecules ranged between 77 and 39%. The 2 cDNAs
      differed in the length of their respective 3' untranslated regions, of 577 bp in
      Cp.F6 and 72 bp in Cp.F10, in both of which a putative polyadenylation signal was
      identified. The structure of the cloned cDNAs, along with genomic Southern blot
      data indicating that eIF-4A is encoded by a single copy gene, strongly suggested
      that Cp.F6 and Cp.F10 reflect a differential 3' end processing of mRNA
      precursors, not observed so far in C. parvum. Northern blot analysis confirmed
      that the sporozoites express 2 eIF-4A mRNAs and showed that the lower molecular
      weight transcript is 10- to 20-fold more abundant. We also investigated the
      polymorphism of the eIF-4A gene and defined a novel polymerase chain reaction
      restriction fragment length polymorphism marker discriminating between C. parvum
      isolates of genotypes 1 and 2.

PMID- 10958457
TI  - Eimeria acervulina infection elevates plasma and muscle 3-methylhistidine levels
      in chickens.
AB  - To assess muscle breakdown during avian coccidiosis, the level of the
      nonmetabolizable amino acid 3-methylhistidine (3MH) was determined in muscle,
      plasma and excreta from chickens infected with Eimeria acervulina. The changes in
      3MH levels during infection were assessed at 1-29 days postinoculation (DPI) in
      animals given 5 x 10(5) oocysts per bird. The effect of levels of parasitism were
      evaluated at 8 DPI in birds receiving 5 x 10(3), 5 x 10(4), 5 x 10(5) or 1 x
      10(6) oocysts each. The 3MH levels of plasma, muscle, and excreta samples were
      determined by high-pressure liquid chromatography after derivatization with
      fluorescamine. Weight gains, breast muscle weight, eviscerated weight, plasma
      carotenoid levels, dry weight of muscle, and gross lesion scores were also
      determined. Infected birds had significantly elevated plasma and muscle 3MH at 4
      and 8 DPI following a single dose of E. acervulina. The increase in 3MH levels
      had an inverse relationship with the time course of weight gain and plasma
      carotenoid levels. Plasma and muscle 3MH levels returned to control values by 15
      DPI and remained unchanged from control values through the remainder of the
      experiment (29 DPI). Breast weight was decreased in infected birds, but the ratio
      of breast weight to eviscerated body weight was unchanged. Excretion of 3MH
      decreased relative to controls at 4 and 8 DPI and returned to control levels on
      15 DPI. The plasma and muscle levels of 3MH were related to severity of
      infection; however, levels of excreted 3MH were not. The results suggested that
      muscle breakdown, as assessed by plasma and muscle levels of 3MH, increased
      during the acute stage of E. acervulina infection. The underlying causes for this
      muscle breakdown was unclear but could involve a physiological response to
      anorexia and decreased food intake during the acute phase of infection. Levels of
      excreted 3MH did not increase during infection and this may be the result of
      decreased excreta output during infection. Plasma and muscle levels of 3MH were
      correlated with severity of E. acervulina infections but may not be as sensitive
      an indicator of infection as plasma carotenoid levels or other physiological
      parameters.

PMID- 10958458
TI  - Clonal diversity in the expression and stability of the metastatic capability of
      Leishmania guyanensis in the golden hamster.
AB  - Metastatic disease is a major concern of dermal leishmaniasis caused by
      Leishmania of the Viannia subgenus. The golden hamster provides an experimental
      model of systemic dissemination and cutaneous metastasis of Leishmania Viannia.
      We have exploited this model to examine the expression of parasite virulence in
      cloned populations derived from a strain of L. guyanensis previously shown to be
      highly metastatic in the hamster. Metastatic capacity manifested as dissemination
      throughout the lymphoid organs; cachexia and secondary cutaneous lesions were
      found to differ among clones, yielding a spectrum of virulence. The metastatic
      phenotype of clonal populations was stable over 5 sequential passages in
      hamsters. In addition, the low or high propensity to disseminate and produce
      cutaneous metastatic lesions was reproduced. Capacity to disseminate from the
      inoculation site was conserved following subcloning of metastatic clones that had
      been passaged in culture for several generations; clinical manifestations,
      cachexia, and cutaneous metastatic lesions were variably expressed. Dissemination
      of parasites and cachexia were significantly related (P = 0.004). Overall,
      cachexia was an earlier manifestation of dissemination than cutaneous metastases
      (P < 0.001). The reproducible expression of virulence phenotypes by discrete
      populations of Leishmania in the golden hamster provides an experimental model
      for clinically relevant expression of virulence in human leishmaniasis.

PMID- 10958460
TI  - Contracaecum multipapillatum (Nematoda: Anisakidae) from Egretta alba (Aves:
      Ardeidae) and comments on other species of this genus in Argentina.
AB  - During a parasitological survey of aquatic birds in Mar Chiquita coastal lagoon
      (Buenos Aires province, Argentina), specimens of Contracaecum Raillet & Henry,
      1912 sp. were found in the esophagus and stomach of the great egret Egretta alba
      (Gmelin, 1789) (Aves: Ardeidae). The nematodes were identified as Contracaecum
      multipapillatum (Drasche, 1882) on the basis of the following features: ratio of
      ventricular appendage length to esophagus length, ratio of intestinal caecum
      length to esophagus length, spicule lengths, number and arrangement of
      postcloacal papillae (3-4 pairs of adanal papillae, 1 double pair, and a
      subterminal group of 2 subventral and 3 sublateral pairs). A complete description
      of the adult specimens of C. multipapillatum is given in the present paper,
      together with a discussion regarding the validity of other species of
      Contracaecum reported from Argentina. Contracaecum philomultipapillatum Labriola
      and Suriano, 1996 is reduced to a junior synonym of C. multipapillatum, and
      Contracaecum longicaecum Schuurmans Sterkhoven, 1952 is considered a species
      inquirenda. A revision of Contracaecum spheniscus Boero and Led, 1970 based on
      appropriate material is necessary.

PMID- 10958459
TI  - Giardia lamblia rearranges F-actin and alpha-actinin in human colonic and
      duodenal monolayers and reduces transepithelial electrical resistance.
AB  - The mechanisms of epithelial injury in giardiasis remain unknown. The effects of
      live Giardia lamblia on cellular G-actin, F-actin, alpha-actinin, and electrical
      resistance of human intestinal epithelial monolayers were investigated using SCBN
      and Caco2 cell lines grown on chamber slides or Transwell filter membranes. In
      separate experiments, some monolayers were also exposed to sonicated
      trophozoites, some to supernatant from live G. lamblia cultures, and some with or
      without the Ca2+ channel blocker verapamil. After 2, 24, or 48 hr of coincubation
      with G. lamblia, monolayers were assessed for cytoskeletal arrangement under
      fluorescence and confocal laser microscopy, and transepithelial electrical
      resistance was measured. Exposure to live G. lamblia trophozoites induced
      localized condensation of F-actin and loss of perijunctional alpha-actinin while
      G-actin remained unchanged. Confocal laser microscopy indicated that F-actin
      rearrangement was not affected by verapamil and was localized within the terminal
      web area. Coincubation of monolayers with G. lamblia lysates or with spent medium
      alone similarly rearranged F-actin. Verapamil alone did not alter F-actin.
      Electrical resistance of SCBN and Caco2 monolayers exposed to G. lamblia was
      significantly decreased versus controls regardless of whether live or lysed
      trophozoite samples were used. The results indicate that G. lamblia-induced
      epithelial injury is associated with F-actin and alpha-actinin rearrangements in
      the terminal web area via mechanisms independent of extracellular Ca2+. These
      alterations are associated with reduced transepithelial electrical resistance and
      are due at least in part to trophozoite products.

PMID- 10958461
TI  - A new species of Sprostoniella Bychowsky and Nagibina, 1967 (Monogenea:
      Capsalidae) from Chaetodipterus zonatus (Osteichthyes: Ephippidae) in Chamela
      Bay, Mexico.
AB  - A new species of Sprostoniella is described from the gills of Chaetodipterus
      zonatus in Chamela Bay, on the west coast of Mexico. The new species differs from
      the 2 previously described congeners by having smaller testes each of which is
      not nearly as long as the ovary. It further differs from the type species,
      Sprostoniella multitestis, by having a poorly developed pair of accessory
      sclerites and the cecal diverticula are not confluent posteriorly. The new
      species also differs from Sprostoniella micrancyra, the other species of the
      genus, by having a shorter peduncle, the glands of Goto are smaller than the
      testes and ovary, and by having a slightly different haptoral structure, with 1
      pair of hamuli rather than 2 pairs, and 1 central haptoral loculus instead of 2
      loculi.

PMID- 10958462
TI  - Helminth parasites of the western painted turtle, Chrysemys picta belli (Gray),
      including Neopolystoma elizabethae n. sp. (Monogenea: Polystomatidae), a parasite
      of the conjunctival sac.
AB  - Neopolystoma elizabethae n. sp. is described from the conjunctival sac of the
      western painted turtle Chrysemys picta belli (Gray), from the Upper Peninsula of
      Michigan. This is the first species found in this location from chelonians in
      North America. The new species differs from all other species of Neopolystoma in
      possessing a circle of 8 genital spines that are recurved and possess a crescent
      shaped base. Eight additional species of helminths were found in the 5 turtles
      examined in this study. All are common parasites of North American freshwater
      turtles. An additional species of Monogenea (Polystomoidespauli) was found in the
      oral cavity. Four species of Digenea (Eustomos chelydrae, Allassostomoides
      chelydrae, Spirorchis kirki, and Spirorchis parvus) and 3 species of Nematoda
      (Spiroxys contorta, Serpinema trispinosus, and Amphibiocapillaria serpentina)
      were also found. The following are reported from Michigan for the first time: P.
      pauli, S. kirki, and A. serpentina.

PMID- 10958463
TI  - Two new rhabditida species (Nematoda: Rhabditidae) parasites of Cyclocephala
      signaticollis (Coleoptera: Scarabaeidae) in Argentina.
AB  - Two different Rhabditida species (Nematoda: Rhabditidae) Parasitorhabditis
      platidontus n. sp. and Cruznema campestris n. sp. are described and illustrated
      from the larvae of Cyclocephala signaticollis (Coleoptera: Scarabaeidae) from
      Buenos Aires province, Argentina. Parasitorhabditis platidontus n. sp. is
      characterized by having 4 odontoplates in the stoma and the vulva is at 80% of
      the length of the body. Cruznema campestris n. sp. can be distinguished by the
      presence of 4 odontoplates and the arrangement of the male genital papillae, 9
      pairs, of which 4 are preanal and 5 postanal.

PMID- 10958464
TI  - Sequencing a specific kinetoplast DNA fragment of Leishmania donovani for
      polymerase chain reaction amplification in diagnosis of leishmaniasis in bone
      marrow and blood samples.
AB  - A set of oligonucleotide primers I and II was developed by analyzing the
      specificity of a cloned kinetoplast DNA (kDNA) fragment of Leishmania donovani
      and sequencing the fragment. Polymerase chain reaction (PCR) was conducted with
      the primers to amplify a minicircle kDNA fragment (297 bp) to detect L. donovani
      in the bone marrow (22 samples), whole blood (16 samples), and serum (17 samples)
      of 22 patients with visceral leishmaniasis. All of 22 patients were diagnosed by
      microscopic identification. Control samples of bone marrow, whole blood, and
      serum were obtained from patients with leukemia and from healthy volunteers. In
      addition, 12 dogs were infected with L. donovani promastigotes for the PCR test.
      The total number of patients positive by PCR testing was 95.5% (21/22), with
      91.0% (20/22) from the bone marrow, 68.8% (11/16) from the blood, and 29.4%
      (5/17) from the sera. Similar results were obtained in infected dogs. No
      amplification products were seen in control samples from humans or dogs. Our
      results suggest that PCR may be useful in detecting kDNA in the bone marrow and
      blood of patients with visceral leishmaniasis.

PMID- 10958465
TI  - A quantitative competitive polymerase chain reaction assay for the oyster
      pathogen Perkinsus marinus.
AB  - A quantitative competitive polymerase chain reaction (QCPCR) assay was developed
      for the oyster parasite Perkinsus marinus. PCR primers for the rRNA gene region
      of P. marinus amplified DNA isolated from P. marinus but not from Perkinsus
      atlanticus, Crassostrea virginica, or the dinoflagellates Peridinium sp.,
      Gymnodinium sp., or Amphidinium sp. A mutagenic primer was used to create a
      competitor plasmid molecule identical to the P. marinus target DNA sequence
      except for a 13-bp deletion. Both P. marinus and competitor DNA amplified with
      equivalent efficiencies. Each of 25 oysters was processed by 5 P. marinus
      diagnostic methods--Ray's fluid thioglycollate medium (FTM) tissue assay, FTM
      hemolymph assay, whole oyster body burden assay, QCPCR of combined gill and
      mantle (gill/mantle) tissue, and QCPCR of hemolymph. The QCPCR assay enabled
      detection of 0.01 fg of P. marinus DNA in 1.0 microg of oyster tissue. QCPCR of
      gill/mantle tissue or hemolymph as well as the body burden assay detected
      infections in 24 of 25 oysters. Ray's FTM tissue assay detected only 19
      infections. The FTM hemolymph assay detected only 22 infections. Regression
      analysis of QCPCR results and FTM results indicated that the QCPCR assays were
      effective in quantitating P. marinus infections in oyster tissues.

PMID- 10958466
TI  - DNA fingerprinting of Cryptosporidium parvum isolates using amplified fragment
      length polymorphism (AFLP).
AB  - The genetic variability of 10 Cryptosporidium parvum isolates of human and animal
      origin was investigated using amplified fragment length polymorphism (AFLP).
      Analysis of fluorescent dye-labeled amplified products was carried out using an
      ABI PRISMS 377 DNA sequencer and ABI PRISMS GeneScan software. One-hundred and
      twelve primer combinations were evaluated using a single C. parvum isolate. The
      patterns generated were highly reproducible. For subsequent study, a subset of 9
      primer pairs that yielded 30-90 DNA fragments after the polymerase chain
      reaction, within the size range of 50-500 bp, was used to screen the 10 C. parvum
      isolates, including 7 bovine, 1 equine, and 2 of human origin. The animal
      isolates produced identical fingerprint patterns with every primer combination
      tested. Of the 2 human isolates tested, 1 of the isolates, passaged in calves,
      generated the same AFLP DNA banding patterns as the animal isolates, whereas the
      other isolate, obtained directly from human feces, produced unique patterns.
      Polymorphism, detected by comparison of the fingerprint patterns of the latter
      human isolate with the common pattern shared by all other isolates, ranged from
      17 to 35% for the 9 primer pairs. The results show that AFLP is a useful method
      for differentiating C. parvum isolates into 2 distinct genotypes.

PMID- 10958468
TI  - Small-scale isolation of high molecular weight DNA from Leishmania braziliensis.
AB  - In this paper, we report a method for isolation of high molecular weight DNA from
      Leishmania promastigotes. This technique is especially indicated for small-scale
      purification of DNA suitable for the construction of highly representative
      genomic libraries. In our protocol, lysis buffer is compatible with RNase
      treatment, avoiding an additional precipitation step and consequent shearing of
      DNA. In order to prove the quality of the DNA isolated by this method, a
      Leishmania braziliensis genomic library was constructed, and an L. braziliensis
      KMP-11 gene was cloned after screening the library with a heterologous probe.

PMID- 10958467
TI  - Suppression of multiple sclerosis in the rat during infection with Trichinella
      pseudospiralis.
AB  - Injection of the rat with guinea pig myelin basic protein (MBP) induces an
      inflammatory demyelination that leads to development of a condition mimicking
      human multiple sclerosis (MS), including severe depressions in mobility,
      coordination, and strength in the affected animal. This model was used to observe
      and compare the antiinflammatory effects of the intestinal and late migratory
      phases of infection with Trichinella pseudospiralis on development of MBP
      induced, MS-like debilitation in rats. Animal performance was measured in an
      activity monitor and in a series of physical tests designed to assess animal
      coordination and strength. Uninfected animals injected with MBP showed declines
      in mobility, coordination, and strength typical for this model. These changes
      were similar in rats infected so that the intestinal phase of infection coincided
      with the peak of MBP-induced debilitation. Rats infected so that the late
      migratory phase of infection occurred during the period of peak MBP-induced
      debilitation showed significantly higher performance scores in mobility,
      coordination and strength compared to the latter 2 groups. These finding
      demonstrate the potency of the anti-inflammatory effects of elevations in host
      corticosteroids seen during the migratory phase of infection with T.
      pseudospiralis.

PMID- 10958469
TI  - Archeological evidence of parasitic infection from the 19th century company town
      of Fayette, Michigan.
AB  - Archeological deposits from the 19th century company town of Fayette, Michigan
      were analyzed for evidence of endoparasitic infection in the human population
      residing in the town between 1867 and 1891. Three privies were associated with
      upper-income and middle-income neighborhoods; 2 household refuse disposal areas
      were found in a predominately lower-income immigrant working class neighborhood.
      Sediment samples from 2 privies associated with dwellings in the middle-income
      neighborhood were positive for eggs of the human whipworm Trichuris trichiura.
      The parasite was probably also present among residents of the lower income
      neighborhood, but the shallow nature of the refuse deposits in that locality
      precluded preservation of the eggs. Contemporary epidemiologic studies of
      helminth infections support the belief that T. trichiura may have been a common
      parasite of 19th century school-age children given the natural inclination of
      young children to defecate indiscriminately, play freely in the dirt, and eat
      without washing their hands.

PMID- 10958470
TI  - The origin of Lecithodesmus (Digenea: Campulidae) based on ND3 gene comparison.
AB  - Species of Lecithodesmus (Campulidae) occur almost exclusively in baleen whales
      throughout a wide geographical distribution. Other campulids occur only in
      odontocetes and, secondarily, in pinnipeds and the sea otter. Therefore, the
      ancestor of Lecithodesmus might have either cospeciated with mysticetes during
      the early divergence of mysticete and odontocete cetaceans or originated later
      via host switching. We evaluate both possibilities based on a phylogenetic
      analysis. The ND3 mitochondrial gene sequence of a species of Lecithodesmus was
      included in a previous partial molecular phylogeny of the Campulidae. Fasciola
      hepatica and Dicrocoelium dendriticum were used as outgroups. Maximum parsimony,
      neighbor-joining, and maximum likelihood methods indicated a nonbasal position of
      Lecithodesmus sp. in the tree, suggesting that the ancestor of Lecithodesmus
      colonized mysticetes from campulids of odontocetes. This result emphasizes the
      importance of host-switching processes in the development of the helminth fauna
      of marine vertebrates, as previously suggested.

PMID- 10958471
TI  - Detection of Cryptosporidium oocysts in bivalve molluscs destined for human
      consumption.
AB  - Clams (Dosinia exoleta, Ruditapes philippinarum, Venerupis pullastra, Venerupis
      rhomboideus, Venus verrucosa), mussels (Mytilus galloprovincialis), and oysters
      (Ostrea edulis) were tested for the presence of Cryptosporidium sp. oocysts using
      various stain techniques and a commercially available kit containing fluorescein
      isothiocyanate-conjugated monoclonal antibodies. All molluscs were harvested in
      northwest Spain (Galicia) except for R. philippinarum, which was from Italy, and
      1 of the 6 oyster samples, which was from England. The results showed the
      presence of Cryptosporidium sp. oocysts in all of the molluscan species destined
      for human consumption.

PMID- 10958472
TI  - Influence of host size and sex on the endohelminth infracommunities of the red
      rockfish Sebastes capensis off Northern Chile.
AB  - The relationship between host size and sex and the abundance, prevalence, species
      richness, diversity, and total number of parasites in the infracommunities of
      Sebastes capensis was analyzed. Nine helminth species were obtained from 180 red
      rockfish captured off Coquimbo Bay, Northern Chile. These included the digeneans
      Pseudopecoelus sp., Diphtherostomum sp., Derogenes sp., Podocotyloides sp., and
      Lecithochirium sp., the acanthocephalan Corynosoma sp., and the nematodes
      Ascarophis sebastodis, Hysterothylacium sp., and Anisakis sp. The abundances of
      Pseudopecoelus sp. and Anisakis sp. were significantly and positively correlated
      with the size of S. capensis, while Corynosoma sp. correlated negatively with
      host size. Only prevalence of Anisakis sp. increased with host size. The number
      of parasite individuals increased significantly with size of S. capensis.
      However, species richness and diversity of the infracommunities was not affected
      by host size. These results suggest that red rockfish > 18 cm do not undergo
      significant ontogenetic changes in their diet. Host sex did not seem to affect
      abundance and prevalence of infections. The presence of Derogenes sp. and
      Podocotyloides sp. are new records of digeneans for S. capensis.

PMID- 10958473
TI  - Detection of Toxoplasma gondii by polymerase chain reaction in sera of acutely
      infected mice.
AB  - The presence of Toxoplasma gondii DNA was detected in sera of acutely infected
      mice by polymerase chain reaction. Adult mice were inoculated intraperitoneally
      with 5 x 10(3) T. gondii RH strain tachyzoites. Five mice were killed every 3 hr
      from 3 to 21 hr post infection (PI) and every day from 1 to 7 days PI. Toxoplasma
      gondii DNA was first detected in 60% of the infected mice 18 hr PI and in 100% of
      the animals 21 hr PI and from 1 to 7 days PI. No mice survived longer than 7
      days.

PMID- 10958474
TI  - Identification and partial characterization of excretory/secretory products with
      proteolytic activity in Giardia intestinalis.
AB  - This report examines the presence of proteolytic activity detected in media
      collected from in vitro cultures of Giardia intestinalis, and the partial
      characterization by gelatin-substrate polyacrylamide gel electrophoresis and
      inhibition studies. Gelatin-substrate polyacrylamide gel electrophoresis revealed
      6 bands with proteolytic activity, with estimated molecular weights of 36, 59,
      63, 72, 103, and 175 kDa. These bands were not present in the control medium. On
      the other hand, G. intestinalis trophozoite lysates showed proteolytic bands at
      16, 20, 66, 82, 108, and 120 kDa, thus indicating that intracellular proteases
      could be different from the excretory/secretory (E/S) products. Based on
      inhibition studies, 2 bands of 59 and 63 kDa were inhibited by iodoacetic acid,
      indicating the presence of cysteine proteases. Partial inhibition of a band of 36
      kDa was found with EDTA, a metal-chelating agent, suggesting the possible
      presence of metalloproteases. The presence of aspartic and serine proteases were
      not detected under the assay conditions used. As G. intestinalis E/S may be
      involved in differentiation mechanisms of the parasite and also be responsible
      for the mucosal alterations that occur in giardiasis, the characterization of
      these proteases may facilitate their evaluation as targets in the therapy of the
      disease.

PMID- 10958476
TI  - Molecular detection and phylogenetic placement of a microsporidian from English
      sole (Pleuronectes vetulus) affected by X-cell pseudotumors.
AB  - Flatfish tissue samples exhibiting X-cell pseudotumors were tested with a number
      of ribosomal DNA (rDNA) general primers in polymerase chain reactions (PCRs).
      Microsporidian primers resulted in the amplification of an rDNA fragment and
      molecular phylogenetic analysis indicated that although the organism did not
      relate closely with any current microsporidian genera, it was most similar to
      Nucleospora salmonis and branched within the Enterocytozoonidae. Re-examination
      of the original tissues used for DNA extractions revealed the presence of
      putative microsporidian spores in PCR-positive samples. These observations
      reiterate the highly sensitive diagnostic feature of PCR, allowing detection of
      organisms overlooked by conventional methods and demonstrate the occurrence of
      rare, coinfecting organisms.

PMID- 10958475
TI  - Immunoblot analysis of trypomastigote excreted-secreted antigens as a tool for
      the characterization of Trypanosoma cruzi strains and isolates.
AB  - An analysis of antibody recognition of Trypanosoma cruzi exoantigens by
      immunoblotting revealed a unique banding pattern that seems to be characteristic
      of each strain or isolate. Trypomastigote excreted-secreted antigens (TESA)
      present in supernatants of LLC-MK2 cells infected with 5 strains and 10 isolates
      of T. cruzi produced 13 different immunoblotting patterns. The same bands were
      observed when probed with acute-phase Chagas' disease serum or with serum from a
      rabbit immunized with the repetitive domain of T. cruzi transialidase recombinant
      protein (anti-shed acute-phase antigens). Three similar patterns were observed
      with TESA from 3 human isolates that probably belong to the same T. cruzi strain.
      When clone CL Brener, clone CL-14, and CL parental strain were analyzed, the same
      bands were observed, although they presented different biological behavior. These
      results suggest that immunoblotting analysis of TESA may be a useful tool for
      characterization of T. cruzi strains and isolates.

PMID- 10958477
TI  - First record of an actinosporean (Myxozoa) in a marine polychaete annelid.
AB  - The marine polychaete Nereis (Hediste) diversicolor (Annelida) from shallow water
      in the Oresund, Denmark, was found to be infected with an actinosporean stage of
      a myxozoan parasite. The body length of the pyriform actinospore is 12-16 microm
      and its maximum width is 10-12 microm. The spore is triangular in apical view,
      with the 3 spherical polar capsules distally. The spore is without caudal
      processes. Eight spores develop in each pansporocyst. Free spores and
      pansporocysts were found in the musculature and parapodia but not in the
      intestine. The myxosporean stage in fish is unknown. This is the first record of
      an actinosporean stage in a marine polychaete, but because marine oligochaetes
      are rare, compared with polychaetes, the latter are believed to play an important
      role as invertebrate (alternate) hosts in marine myxozoan life cycles.

PMID- 10958478
TI  - Oxidase activities in macrocyclic-resistant and -susceptible Haemonchus
      contortus.
AB  - The role of oxidative metabolism in resistance to macrocyclic lactones in
      Haemonchus contortus was examined by measuring activities toward 2 model
      cytochrome P450 substrates, aldrin and ethoxycoumarin, in a susceptible and a
      resistant isolate of the parasite. Microsomal preparations from larvae and adults
      of the 2 isolates showed no differences in levels of NADPH- or cumene
      hydroperoxide-supported aldrin epoxidase or ethoxycoumarin O-deethylase
      activities. Intact adult nematodes showed an ability to catalyze the epoxidation
      of significant amounts of aldrin, although the nature of the enzyme group
      responsible was unknown. This epoxidase activity was greater in adults of the
      susceptible isolate. It is apparent that oxidase activities toward the 2
      substrates are not enhanced in the resistant isolate, suggesting that the
      observed resistance to macrocyclic lactones may not involve enhanced oxidative
      metabolism.

PMID- 10958479
TI  - Sarcocystis muris possesses both diheteroxenous and dihomoxenous characters of
      life cycle.
AB  - The cystozoites of Sarcocystis muris were infective to other mice after peroral
      inoculation. They transformed into gamonts and after fertilization underwent
      sporulation with the production of infectious oocysts/sporocysts in the lamina
      propria of the small intestine. The present study demonstrated that S. muris
      possesses both diheteroxenous and dihomoxenous life cycle and can be transmitted
      by the cannibalism among mice.

PMID- 10958480
TI  - Prevalence of Toxoplasma gondii antibodies in muskox (Ovibos moschatus) sera from
      northern Canada.
AB  - Prevalence of antibodies to Toxoplasma gondii was determined in 203 muskoxen
      (Ovibos moschatus) from 3 geographically distinct areas of northern Canada (near
      the hamlets of Kugluktuk and Cambridge Bay, Nunavut and Holman, Northwest
      Territories) by the modified agglutination test (MAT). Antibodies were found in
      13 (6.4%) of 203 animals with MAT titers of 1:25 in 2, 1:50 in 7, 1:200 in 2,
      1:400 in 1, and 1:800 in 1. The 4 muskoxen with MAT titers > or =1:200 were adult
      females and were among 10 animals examined from a mainland population near
      Kugluktuk. The seroprevalence was lower in Victoria Island muskoxen collected
      near Cambridge Bay (4.6% of 151) and Holman (4.8% of 42). This is the first
      serologic survey for T. gondii infection in muskoxen.

PMID- 10958481
TI  - Growth of the genital primordium as a marker to describe a time course for the
      heterogonic larval development in Strongyloides stercoralis.
AB  - A time course for the heterogonic development of Strongyloides stercoralis is
      described and a method for distinguishing the early larval stages of this
      nematode is proposed. The number of cells in the developing gonad were counted at
      various time intervals of incubation, along with the percentage of larvae in molt
      at each interval. The time course of growth of the gonad follows a pattern
      comparable to that reported for body length in an idealized general nematode. A
      model for the heterogonic development of S. stercoralis is proposed, which,
      although similar to other nematode developmental models, is stage specific for S.
      stercoralis, allowing the otherwise morphologically similar rhabditiform stages
      (L1, L2) to be distinguished.

PMID- 10958482
TI  - Infection of immunosuppressed C57BL/6N adult mice with a single oocyst of
      Cryptosporidium parvum.
AB  - The present study was designed to determine the minimum number of Cryptosporidium
      parvum oocysts capable of producing patent infections in immunosuppressed
      C57BL/6N adult mice. Sixty-four female mice were divided into 6 groups of 8 mice
      each, except group 1 that contained 24 mice. Mice in groups 1-3 were
      immunosuppressed with dexamethasone and inoculated with 1, 5, and 10 oocysts per
      mouse, respectively. The accuracy of the inoculum size was microscopically
      confirmed. Mice in groups 4-6 served as controls: they received either only
      oocyst inoculation (group 4), or immunosuppression (group 5), or no treatments
      (group 6). Fecal oocyst shedding was monitored daily for each mouse using an
      indirect immunofluorescent assay. Parasite colonization in the terminal ileum of
      each mouse was evaluated histologically. Four of 24 mice in group 1 developed
      patent infections, with a prepatent period of approximately 6 days. All mice in
      groups 2 and 3 developed patent infections, with prepatent periods ranging from 4
      to 7 days. Mice in groups 4-6 remained uninfected. Parasite colonization was
      observed in the terminal ilea of all mice in groups 1-3 that shed fecal oocysts.
      The present study experimentally demonstrates that a single viable oocyst can
      induce patent C. parvum infections in immunosuppressed C57BL/6N adult mice and
      indicates that this mouse model could be used for the parasite genotype or
      isolate cloning.

PMID- 10958483
TI  - Genotyping of Giardia lamblia isolates from humans in China and Korea using
      ribosomal DNA Sequences.
AB  - Genetic characterization of a total of 15 Giardia lamblia isolates, 8 from Anhui
      Province, China (all from purified cysts) and 7 from Seoul, Korea (2 from axenic
      cultures and 5 from purified cysts), was performed by polymerase chain reaction
      amplification and sequencing of a 295-bp region near the 5' end of the small
      subunit ribosomal DNA (eukaryotic 16S rDNA). Phylogenetic analyses were
      subsequently conducted using sequence data obtained in this study, as well as
      sequences published from other Giardia isolates. The maximum parsimony method
      revealed that G. lamblia isolates from humans in China and Korea are divided into
      2 major lineages, assemblages A and B. All 7 Korean isolates were grouped into
      assemblage A, whereas 4 Chinese isolates were grouped into assemblage A and 4
      into assemblage B. Two Giardia microti isolates and 2 dog-derived Giardia
      isolates also grouped into assemblage B, whereas Giardia ardeae and Giardia muris
      were unique.

PMID- 10958484
TI  - Snail size as a determinant of prepatent period duration in Helisoma anceps
      infected with Halipegus occidualis (Digenea: Hemiuridae).
AB  - Pulmonate snails (Helisoma anceps) of varying sizes were exposed to 2, 4, 8, or
      16 eggs of Halipegus occidualis and observed over several months to determine the
      duration of the prepatent period. Infection probability was positively correlated
      with number of eggs ingested. The number of eggs ingested did not, however, have
      a significant effect on the duration of the prepatent period, presumably because
      low infectivity of the eggs (15%) dictated that most patent infections arose from
      a single miracidium. There was a significant, positive correlation between snail
      length (measured at time of exposure) and duration of prepatent period,
      suggesting that density-dependent effects are, in part, responsible for the
      initiation of cercariae production in H. occidualis.

PMID- 10958485
TI  - Duration of infection of jirds (Meriones unguiculatus) with Trichostrongylus
      colubriformis.
AB  - Jirds (Meriones unguiculatus) were infected with 700 infective larvae (L3) of
      Trichostrongylus colubriformis. The fecal egg counts (epg) were followed
      regularly until 340 days postinoculation, and worm numbers were determined on
      necropsy at 315 and 350 days postinoculation. The epg increased to a peak of
      2,600 on day 24 postinoculation. Thereafter, the epg showed continuous decrease
      from day 31 until day 318 postinoculation. The rates of inoculum recovery were
      0.29-1.43% on day 315 and 0.142-0.428% on day 350 postinoculation. On day 315
      postinoculation, 12 male worms were recovered from 2 of 3 animals necropsied. On
      day 350 postinoculation, all 6 animals were infected, and 6 female and 4 male
      worms were recovered. The systemic IgM, IgG, and intestinal mucous IgA responses
      were significantly higher in infected groups compared with negative control
      groups necropsied on 315 and 350 days postinoculation (P < 0.001). These results
      confirm that the T. colubriformis-jird system is a useful model for studies on
      the various host-parasite relationships of chronic trichostrongylosis.

PMID- 10958486
TI  - Natural and experimental infection of normal cattle with Escherichia coli O157.
AB  - The objective of the study was to determine the effects of inoculating cattle
      orally with a strain of Escherichia coli O157:H7 (A84/92). However, before they
      were challenged two of the six calves were found to be infected naturally with a
      wild-type strain of E coli O157 and two more of them became infected later. The
      number of daily faeces samples from which the wild-type E coli O157 was isolated
      ranged from one to 10. After they were inoculated, A84/92 was detected in all the
      calves' faeces on one to six of the next 14 days, and later from the faeces
      samples of three calves on two, three, and 11 occasions, the last occasion being
      between 19 and 51 days after inoculation. Two calves were redosed with A84/92,
      and the organism was isolated on a further five and 15 occasions, the last being
      after 20 and 58 days. In three dry cows, A84/92 was isolated from the faeces on
      three to 11 of the 14 days after they were inoculated. Two of the cows were
      redosed and from one of them it was isolated on 15 occasions, the last being 44
      days after the initial infection; in the other cow no further isolation was made.
      In three lactating cows, it was detected on three to four of the 14 days after
      they were inoculated, and similar results were obtained after they were
      reinoculated. None of the animals showed clinical signs and no lesions were
      detected in the intestines of the calves. Three calves had a serological response
      to E coli O157 but, with the exception of one cow which had a slight increase to
      IgM levels, no serological changes were observed in the adult cattle.

PMID- 10958487
TI  - Doppler-ultrasonographic detection of retrograde pulsatile flow in the caudal
      vena cava of a puppy with cor triatriatum dexter.
AB  - A three-month-old puppy had ascites, but its heart was normal by auscultation.
      Abdominal ultrasonography revealed an enlarged liver, distended hepatic veins and
      a distended caudal vena cava. Doppler ultrasonography detected retrograde flow in
      the caudal vena cava and abnormally pulsatile flow in the hepatic veins and
      caudal vena cava. A non-selective venogram was used to detect the path of the
      blood from the caudal vena cava. A postmortem examination showed that the puppy
      had cor triatriatum dexter and a defect in the atrial septum.

PMID- 10958489
TI  - Apparent loss of enrofloxacin resistance in bovine Salmonella typhimurium strains
      isolated in Belgium, 1991 to 1998.

PMID- 10958488
TI  - Epidemiological and microbiological study of an outbreak of infectious
      keratoconjunctivitis in sheep.
AB  - After several thousand sheep had been imported from Australia and New Zealand to
      Croatia during 1995, many native sheep that had been in contact with the imported
      animals acquired a severe ocular disease closely resembling infectious
      keratoconjunctivitis. In affected flocks glucose-fermenting mycoplasma were
      isolated from 48 per cent of conjunctival swabs and Branhamella ovis from 58 per
      cent. Twelve of 42 culturally and biochemically identical isolates were
      identified as Mycoplasma conjunctivae by polymerase chain reaction. From the
      conjunctivae of two animals M conjunctivae and M arginini were isolated in mixed
      culture. For many reasons most farmers removed the imported animals from their
      flocks and only sporadic cases of the disease were recognised in 1996. At the end
      of 1997, six flocks which were clinically free of the disease but had been
      affected during 1995, and five flocks with no history of the severe ocular
      disease were examined clinically and microbiologically, and were found to be free
      of M conjunctivae infection. At the time, B ovis was cultured almost exclusively
      from sheep originating from flocks which had been affected during 1995 and/or
      1996. It was usually isolated in pure culture or as the predominant bacterial
      species, and was often accompanied by mild conjunctivitis. There were no
      microbiologically confirmed new cases of infectious keratoconjunctivitis during
      1998 and 1999.

PMID- 10958490
TI  - Intussusception as a complication of rectal prolapse replacement in a ewe.

PMID- 10958491
TI  - Vacuolations in the head of spermatozoa from an infertile ram.

PMID- 10958493
TI  - Decisions on euthanasia.

PMID- 10958492
TI  - Use of lignocaine (lidocaine) in food animals.

PMID- 10958494
TI  - Decisions on euthanasia.

PMID- 10958495
TI  - Decisions on euthanasia.

PMID- 10958496
TI  - Decisions on euthanasia.

PMID- 10958497
TI  - Hunting inquiry.

PMID- 10958498
TI  - Hunting inquiry.

PMID- 10958500
TI  - Euthanasia of large animals.

PMID- 10958499
TI  - Euthanasia of horses.

PMID- 10958501
TI  - RCVS annual retention fee.

PMID- 10958502
TI  - RCVS annual retention fee.

PMID- 10958503
TI  - RCVS annual retention fee.

PMID- 10958504
TI  - RCVS annual retention fee.

PMID- 10958505
TI  - Dew claw removal in Bernese mountain dogs.

PMID- 10958506
TI  - Lymph-node dissection in breast cancer.
AB  - BACKGROUND: Along with the ongoing modifications in treatment of primary breast
      cancer, the purpose and extent of lymph-node dissection has changed. The
      following is an overview of the current knowledge and practice of lymph-node
      dissection in breast cancer, with special regard to expected developments in the
      near future. Axillary dissection is described as a ten-step procedure, including
      dissection of level-I and -II and Rotter's nodes, without level-III nodes,
      providing at least ten lymph nodes for accurate staging information. DISCUSSION:
      Axillary dissection still offers the most efficient local control in node
      positive patients, whereas, in primarily node-negative patients, irradiation
      seems to be equally effective. In general, lymph-node dissection does not alter
      overall survival but there is no doubt that surgical therapy still contributes to
      cure in early-breast-cancer patients and seems to be curative for certain
      patients with stage-I carcinoma. The lymph node status of the axilla is crucial
      for the indication of adjuvant therapy in early invasive breast cancer, but an
      increasing number of clinical node-negative patients could be managed with
      information based on features of the primary tumor, regardless of the nodal
      status. The most promising new concept for the selection of node-positive
      patients, while avoiding unnecessary morbidity of axillary dissection in early
      breast-cancer patients, is the sentinel-node concept. The principle is based on
      the identification of the first "sentinel" lymph node reached by lymphatic flow.
      Thus, only proven node-positive patients undergo axillary dissection. Local
      failure of internal mammary lymph nodes is rarely recognized; however, internal
      mammary lymph nodes seem to have an underestimated prognostic significance in
      about 10-20% of axillary node-negative patients. This may lead to the withholding
      of systemic therapy for patients with early breast cancer. Nevertheless, there is
      no indication for a routine parasternal dissection today. The sentinel-node
      concept may also support the selection of diagnostic internal lymph-node biopsy
      and subsequent adjuvant therapy in cases with no axillary lymph-node metastases
      but with internal lymph-node metastases.

PMID- 10958507
TI  - Lymph node dissection in cutaneous melanoma: surgical and oncological
      implications.
AB  - The concept of Sentinel Lymph Node Dissection (SLND) has strongly influenced the
      surgical approach towards primary melanoma in the last decade. Initiated by the
      disappointing results of elective lymph node dissection (ELND) in this
      malignancy, the concept of analyzing the first draining lymph node (Sentinel) of
      a regional basin was developed as a diagnostic means to avoid unnecessary ELND in
      case of negative SLNs. According to recent standards detection of the SLN should
      be performed by a triple approach: injection of 90 nm Technetium and patent blue
      in the periphery of the primary melanoma, and intraoperative tracing of
      radioactivity with the aid of a hand-held gamma probe. Histopathological
      examination of alternating series sections of the whole lymph node appears to be
      the best analytic approach. Molecular biologic procedures such as tyrosinase RT
      PCR are time-consuming to perform and produce contradictory results. SLND for
      cutaneous melanoma is an interdisciplinary diagnostic approach involving surgery,
      dermatology, pathology, and nuclear medicine. In spite of a variety of published
      promising results derived from clinical trials ranging from a few dozens to
      several hundred included patients the diagnostic and prognostic value of SLND
      remains to be confirmed by ongoing controlled prospective clinical trials. At
      this stage, SLND can by no means be considered a therapeutic procedure. These
      aspects have to be kept in mind when informed consent is obtained from patients
      as well as in the individual determination of the risk-benefit ratio.

PMID- 10958508
TI  - Principles of sentinel lymph node identification: background and clinical
      implications.
AB  - The management of clinically negative regional lymph nodes in early-stage
      melanoma has been controversial for many years. While some advocate wide excision
      of the primary with elective node dissection (ELND), others recommend excision of
      the primary alone and therapeutic node dissection (TLND) for recurrences in the
      nodal basin. ELND is based on the concept that metastases occur by passage of the
      tumor from the primary to the regional nodes and distant sites, in which case
      early dissection of regional nodes will disrupt metastatic progression and
      prevent the spread of disease. Advocates of the "wait and watch" approach suggest
      that regional node metastases are markers for disease progression and that
      distant disease can occur without node metastases. Four randomized prospective
      studies comparing ELND and TLND have not demonstrated overall survival advantage
      for ELND, but suggest that patients with early regional metastases may benefit
      from ELND. As an alternative, Morton et al., from UCLA and the John Wayne Cancer
      Institute, devised intraoperative lymphatic mapping and sentinel lymphadenectomy
      (LM/SL). These minimally invasive operative procedures allow identification of
      the first and key (sentinel) lymph node (SN). The technique accurately maps the
      lymphatics by lymphoscintigraphy, and vital blue dye leads the surgeon to the SN.
      The pathologist then concentrates on seeking metastases in the nodes most likely
      to contain metastases. Patients with tumor-positive SN undergo completion lymph
      node dissection (CLND), while those without SN metastases avoid the complications
      and costs associated with this procedure. Morton et al., in a report on their
      initial experience of LM/SL, performed CLND in all cases regardless of SN tumor
      status and demonstrated the precise staging capacity of the procedure. Since this
      initial report, numerous studies have validated the accuracy and low morbidity of
      the procedure. Each center must master a learning phase. The procedure is
      dependent on the close cooperation of nuclear medicine physicians, surgeons, and
      pathologists. While LM/SL is now almost standard practice in the US, the results
      of clinical trials are awaited to determine whether LM/SL can replace ELND and
      TLND in the management of early-stage melanoma.

PMID- 10958509
TI  - Minimally invasive video-assisted surgery of the thyroid: a preliminary report.
AB  - BACKGROUND: Endoscopic thyroidectomy has not yet met the favor of most endocrine
      surgeons. We evaluated the technical feasibility of a video-assisted approach to
      thyroid surgery. PATIENTS AND METHODS: The study group comprised 22 females and 5
      males, all with a single thyroid nodule. The nodule was "hot" in 4 patients,
      microfollicular in 17 and with Hurthle cell cytology in 6. A 15-mm skin incision
      was made above the sternal notch. The midline was opened and a 12-mm trocar
      inserted into the thyro-tracheal groove. It was inflated with CO2 for 3 min. The
      trocar was then removed and the procedure performed using external retractors and
      needlescopic instruments. The upper pedicle was dissected. Identification of
      recurrent nerve and parathyroid glands was facilitated by endoscopic
      magnification. The upper gland portion was then retracted out of the operative
      cavity; inferior veins were ligated and the lobe entirely extracted and
      dissected. Frozen section was obtained for "cold" nodules. RESULTS: Video
      assisted hemithyroidectomy was accomplished in 24 patients; 1 underwent video
      assisted total thyroidectomy (positive frozen section). Cervicotomy was required
      once to achieve hemostasis and once to perform total thyroidectomy (positive
      frozen section). Mean operative time was 82 min (range 60-120 min). No
      complications were registered. The cosmetic result was excellent. CONCLUSIONS:
      Video-assisted thyroid surgery is feasible and may improve cosmetic outcome;
      total thyroidectomy can be accomplished through the same access point.

PMID- 10958510
TI  - Primary and secondary hepatic manifestation of neuroendocrine tumors.
AB  - BACKGROUND: In comparison with most other malignancies, in the treatment of
      metastatic neuroendocrine tumors one also has to consider endocrine symptoms and
      natural progression of disease. Since hepatic metastasis predominates and
      endocrine symptoms correlate with functional tumor mass, hepatic resection may
      improve prognosis or even cure patients. PATIENTS AND METHODS: We reviewed 41
      consecutive patients with metastatic neuroendocrine tumors and four patients with
      primary hepatic disease presenting between 1989 and 1999. The neuroendocrine
      tumors were classified according to their origin, pattern of metastasis,
      endocrine activity, and histology. Operative therapy including hepatic resections
      of different extent, liver transplantation, and removal of the primary tumor was
      analyzed. The median survival after initial diagnosis and after hepatic resection
      were major parameters of outcome. RESULTS: There were 26 low-grade malignant, 12
      high-grade malignant, 2 biphasically differentiated neuroendocrine carcinomas,
      and 5 pancreatic endocrine tumors. Hepatic resections were performed in 25
      patients, resections of the primary tumor in 40 patients. The median survival
      after initial diagnosis was 49 months; 50.5 months in patients with hepatic
      resection versus 47 months in those with no liver surgery. CONCLUSION: Hepatic
      resection improved the outcome of patients with liver metastasis due to
      neuroendocrine tumors tendentiously but not significantly.

PMID- 10958511
TI  - The role of carcinoembryonic antigen for the detection of recurrent disease
      following curative resection of large-bowel cancer.
AB  - BACKGROUND AND AIMS: During recent years, a discussion about cost-effectiveness
      and importance of follow-up evaluation after curative resection of large-bowel
      cancer has developed. It is not known whether the determination of carcino
      embryonic antigen (CEA) plays a crucial role in the early detection of recurrent
      disease. PATIENTS/METHODS: We conducted an analysis of the prospective follow-up
      database of 1321 patients after curative resection of colorectal cancer in our
      institution between 1990 and 1998 to evaluate the role of CEA in the early
      detection of recurrent disease. RESULTS: Of the 1321 patients included in our
      study, 306 developed recurrent disease following curative resection (23.2%).
      These patients with recurrent disease were divided into: Group I. No pre
      operative CEA determination/insufficient follow-up (n=47; 15.4%). Group II. No
      elevation of CEA with primary cancer (n=156; 51.0%): (IIa) elevation with
      recurrent disease (n=62); (IIb) no elevation at any time point (n=53); and (IIc)
      role of CEA not completely elucidated (n=41). Thirteen patients of group II
      underwent curative relapse surgery (8.3%). Group III. Elevated CEA with primary
      cancer (n=103; 33.7%): (IlIa) no increase with recurrent disease (n=21); (IIIb)
      increase with other symptoms of recurrent disease (n=45); and (IIIc) increased
      values as an early symptom of recurrent disease (n=37). Sixteen patients of group
      III underwent curative relapse surgery (15.5%). In patients after relapse
      surgery, recurrent disease developed again after a median time of 12 months (mean
      17.9+/-3.8 months). CONCLUSIONS: Our findings indicate that 2.8% of all patients
      (12.1% of patients with recurrent disease) who underwent curative resection of
      colorectal cancer profit from follow-up CEA determinations. With careful
      observation of CEA kinetics, 6.2% (n=82) of all patients or 26.8% of patients
      with recurrent disease could profit from routine follow-up CEA determinations. In
      9.5% of patients with recurrent disease, curative resection of relapse was
      achieved and these patients remained disease free for a median time of 12 months.
      Regular CEA measurements remain an important part of routine patient care after
      curative resection of colorectal cancer.

PMID- 10958512
TI  - The unreamed tibia nail. Multicenter study of the AO/ASIF.
      Osteosynthesefragen/Association for the Study of Internal Fixation.
AB  - In the last 10 years, traumatologists have become more aware of the importance of
      blood supply to fracture fragments for both the healing of fractures and
      prevention of infection. Due to our experience with fractures having severely
      disrupted periosteal blood supply, we are looking more critically at
      intramedullary reamed nailing as a treatment option. This research was a result
      of our increased knowledge of the interplay between periosteal and endosteal
      blood supply.

PMID- 10958513
TI  - Subcutaneous infusion anesthesia with diluted mixtures of prilocain and
      ropivacain.
AB  - BACKGROUND: Local anesthesia often suffices for surgery on the outside of the
      body. In recent years, it has been found that such local anesthesia can be
      adequately carried out using large amounts of highly diluted anesthetic
      solutions. METHODS: Using one or more common infusomats, we injected mixed
      anesthetic solutions slowly, painlessly, paravenously, and automatically via
      subcutaneous infusion anesthesia (SIA) into the subcutaneous layer in a large
      group of patients scheduled for surgery. The local anesthetics used were
      prilocaine and ropivacaine (Xylonest and Naropin); these were diluted with
      original Ringer's solution with epinephrine (1: 1,000,000) in 500-ml bottles. The
      concentration of the mixture varied between 0.3% and 0.08% depending on the
      requirements of surgery. The needles used ranged from 30-gauge to 20-gauge
      needles, with a length of 1.5-10 cm. The speed of injection varied between 30
      ml/h and 1500 ml/h, depending on the location, the requirements of the surgery
      and the needle size. Volumes usually ranged from 2 ml to 600 ml depending on the
      concentrations used. The maximum dose was approximately 4 mg/kg prilocaine and 2
      mg/kg ropivacaine. PATIENTS: We used this technique in preparing for 5020 major
      and minor skin operations in 3270 patients ranging in age from 0.5 years to 95
      years (mean age 54 years). Microbiological tests of the infusion system were
      carried out. Patients were asked about their pain during anesthesia, operation,
      and postoperatively. RESULTS: There were no complications from local anesthesia.
      The technique proved safe and comfortable even for children and very sensitive
      patients. The median duration of postoperative anesthesia was 5 h (maximum 23 h).
      Choosing the concentration, the needle, the needle position, the flow rate, and
      the volume requires some experience.

PMID- 10958514
TI  - Characterization and prevention of phototoxic effects in intravital fluorescence
      microscopy in the hamster dorsal skinfold model.
AB  - Intravital microscopy is widely used to study the microcirculation. However, the
      use of fluorescent dyes can induce phototoxic effects which may affect the
      measurements, particularly in tissue exposed to oxidative stress. The aim of the
      study was to determine the threshold light dose at which fluorescent microscopy
      is associated with phototoxic effects in the hamster dorsal skinfold chamber
      under normal and pathological conditions. The extent of phototoxicity in the
      microcirculation in the hamster skinfold chamber was investigated using
      intravital fluorescent microscopy during 60 min of illumination (1048 mW/cm2)
      applying two different concentrations of fluorescein isothiocyanate dextran under
      baseline conditions (groups A and B) and following 4 h of ischemia (groups C and
      D). In the second part of the study the microvasculature was analyzed regarding
      phototoxic effects during a standardized intravital microscopic examination after
      4 h of pressure induced ischemia. Groups I and II (n=7) were studied using
      epiillumination after injection of fluorescein isothiocyanate dextran plus
      rhodamine 6G or rhodamine 6G only. In group III (n=7) only transillumination was
      used. Arteriolar vasospasm, microvascular perfusion failure, thrombus formation,
      and enhanced leukocyte endothelium interaction were observed as signs of a
      phototoxic effect in normal tissue. However, the light doses needed to induce
      these effects clearly exceeded those during standard examinations. The induction
      of a 4-h ischemia and reperfusion further enhanced these effects. Despite the
      predamage by ischemia/reperfusion the comparison of epiillumination and
      transillumination microscopy using a standard protocol showed no differences
      regarding the parameters analyzed at any time. This indicates that
      epiillumination and the fluorescent dyes per se did not affect the experimental
      results. These results show that ischemia/reperfusion studies in the dorsal
      skinfold chamber of the Syrian golden hamster can be carried out safely without
      the risk of inducing phototoxic effects by fluorescent microscopy. Nevertheless
      every laboratory using epiillumination and fluorescent dyes should take
      precautions to avoid these effects by the use of sensitive cameras to lower the
      light dose.

PMID- 10958515
TI  - Photodynamic treatment of neoplastic lesions of the gastrointestinal tract.
      Recent advances in techniques and results.
AB  - Photodynamic therapy (PDT) is a form of cancer treatment based on the selective
      accumulation of a photosensitizer (by exogenous or endogenous means) in
      neoplastic tissue. Subsequent activation of the photosensitizer by a specific
      wavelength of light results in tumor cell death. Activation of a photosensitizer
      to the appropriate energy state results in the production of singlet oxygen, a
      powerful oxidizing agent. PDT can kill cells by three mechanisms: direct cell
      death by photooxidation, apoptosis, or as a consequence of vascular shutdown. The
      toxicity of PDT is site specific and dependent on the organ being irradiated and
      the selectivity of the photosensitizer for target tissue over normal tissue.
      However, there are also reactions related to the sensitizer per se that are
      independent of those related to the treatment site. Such reactions include
      cutaneous photosensitization, nausea, vomiting, hypotension, and altered liver
      'function' tests. Excitation of photosensitizer by an incident photon produces
      reemission of a fluorescent photon, which can be used to detect a tumor that is
      not ordinarily evident. The major limiting factor in using PDT is the depth of
      tumor kill. The majority of clinical experience involving PDT of the
      gastrointestinal tract involves patients who are considered to be poor operative
      risks, and reported follow-ups after treatment are not only limited but also
      variable.

PMID- 10958516
TI  - Attitude of patients toward transplantation of xenogenic organs.

PMID- 10958517
TI  - Attitude of patients toward transplantation of xenogeneic organs.

PMID- 10958518
TI  - The timing of arm-trunk coordination is deficient and vision-dependent in
      Parkinson's patients during reaching movements.
AB  - The role of the basal ganglia in the coordination of different body segments and
      utilization of motor synergies was investigated by analyzing reaching movements
      to remembered three-dimensional (3D) targets in patients with Parkinson's disease
      (PD). Arm movements were produced alone or in combination with a forward bending
      of the trunk, with or without visual feedback. Movements in PD patients were more
      temporally segmented, as evidenced by irregular changes in tangential velocity
      profiles. In addition, the relative timing in the onsets and offsets of fingertip
      and trunk motions were substantially different in PD patients than in control
      subjects. While the control subjects synchronized both onsets and offsets, the PD
      patients had large mean intervals between the onsets and offsets of the fingertip
      and trunk motions. Moreover, PD patients showed substantially larger trial-to
      trial variability in these intervals. The degree of synchronization in PD
      patients gradually increased during the movement under the influence of visual
      feedback. The mean and variability of the intersegmental intervals decreased as
      the fingertip approached the target. This improvement in timing occurred even
      though the separate variability in the timing of arm and trunk motions was not
      reduced by vision. In combined movements, even without vision, the PD patients
      were able to achieve normal accuracy, suggesting they were able to use the same
      movement synergies as normals to control the multiple degrees of freedom involved
      in the movements and to compensate for the added trunk movement. However, they
      were unable to recruit these synergies in the stereotyped manner characteristic
      of healthy subjects. These results suggest that the basal ganglia are involved in
      the temporal coordination of movement of different body segments and that related
      timing abnormalities may be partly compensated by vision. Abnormal intersegmental
      timing may be a highly sensitive indicator of a deficient ability to assemble
      complex movements in patients with basal-ganglia dysfunction. This abnormality
      may be apparent even when the overall movement goal of reaching a target is
      preserved and normal movement synergies appear to be largely intact.

PMID- 10958519
TI  - The simultaneous coding of orientation and contrast in the responses of V1
      complex cells.
AB  - The responses of 30 V1 complex cells were recorded using a complete set of
      transiently presented, oriented stimuli of different contrasts. A back
      propagation neural network was used to predict the multivariate visual stimuli
      from the neuronal responses on a trial-by-trial basis. For single neurons, the
      strength of the response was much better at predicting the orientation of a
      visual stimulus than its contrast. Using the temporal modulation of the response
      improved the ability to predict the contrast of a stimulus without affecting the
      ability to predict the orientation. Removing stimulus latency from the responses,
      by time-shifting the individual responses an amount equal to the average latency,
      significantly reduced the ability to predict stimulus contrast, demonstrating
      that the response latency is reliable enough, even for a single neuron and a
      single trial, for it to be used to help determine stimulus contrast. Pooling the
      responses from a group of 11 neurons demonstrated that small groups of neurons
      can accurately represent multivariate stimuli in a single trial.

PMID- 10958520
TI  - Relationship between motor activity-related cortical potential and voluntary
      muscle activation.
AB  - The purpose of this study was to investigate the relationship between EEG-derived
      motor activity-related cortical potential (MRCP) and voluntary muscle activation.
      Eight healthy volunteers participated in two experimental sessions. In one
      session, subjects performed isometric elbow-flexion contractions at four
      intensity levels [10%, 35%, 60%, and 85% maximal voluntary contraction (MVC)]. In
      another session, a given elbow-flexion force (35% MVC) was generated at three
      different rates (slow, intermediate, and fast). Thirty to 40 contractions were
      performed at each force level or rate. EEG signals were recorded from the scalp
      overlying the supplementary motor area (SMA) and contralateral sensorimotor
      cortex, and EMG signals were recorded from the skin surface overlying the belly
      of the biceps brachii and brachioradialis muscles during all contractions. In
      each trial, the force was used as the triggering signal for MRCP averaging. MRCP
      amplitude was measured from the beginning to the peak of the negative slope. The
      magnitude of MRCP from both EEG recording locations (sensorimotor cortex and SMA)
      was highly correlated with elbow-flexion force, rate of rising of force, and
      muscle EMG signals. These results suggest that MRCP represents cortical motor
      commands that scale the level of muscle activation.

PMID- 10958521
TI  - Neural correlates of reafference: evoked brain activity during motion perception
      and saccadic eye movements.
AB  - The ability to perceive a stable visual environment despite eye movements and the
      resulting displacement of the retinal image is a striking feature of visual
      perception. In order to study the brain mechanism related to this phenomenon, an
      EEG was recorded from 30 electrodes spaced over the occipital, temporal and
      parietal brain areas while stationary or moving visual stimuli with velocities
      between 178 degrees/s and 533 degrees/s were presented. The visual stimuli were
      presented both during saccadic eye movements and with stationary eyes. Stimulus
      related potentials were measured, and the effects of absolute and relative
      stimulus velocity were analyzed. Healthy adults participated in the experiments.
      In all 36 subjects and experimental conditions, four potential components were
      found with mean latencies of about 70, 140, 220 and 380 ms. The latency of the
      two largest components between 100 and 240 ms decreased while field strength
      increased with higher absolute stimulus velocity for both stationary and moving
      eyes, whereas relative stimulus velocity had no effect on amplitude, latency and
      topography of the visual evoked potential (VEP) components. If the visual system
      uses retinal motion information only, we would expect a dependence upon relative
      velocity. Since field strength and latency of the components were independent of
      eye movements but dependent upon absolute stimulus velocity, the visual cortex
      must use extraretinal information to extract stimulus velocity. This was
      confirmed by the fact that significant topographic changes were observed when
      brain activity evoked during saccades and with stationary eyes was compared. In
      agreement with the reafference principle, the findings indicate that the same
      absolute visual stimulus activates different neuronal elements during saccades
      than during fixation.

PMID- 10958522
TI  - Visual-vestibular interaction in early infancy.
AB  - The development of visual and vestibular control of smooth gaze adjustments was
      studied longitudinally in 3- to 18-week-old infants. Eye and head movements were
      measured with electro-oculography (EOG) and an optoelectronic system,
      respectively. The infant was placed in a chair providing full support to the
      trunk but allowing relatively free head movements. The chair was positioned at
      the center of a striped-patterned drum. The chair and the drum were oscillated
      sinusoidally, either individually or in synchrony at 0.25 Hz. When the drum
      oscillated around the infant (the optokinetic response condition, OKR), the gain
      of both smooth eye and head tracking components was low up to 6 weeks of age,
      after which the eye gain increased dramatically and the lag decreased. The most
      substantial increase in head gain was observed at 13-18 weeks of age. When only
      the chair was oscillated (visual VOR, VVOR), the compensatory eye gain was high
      at 3 weeks and the head contributed significantly to the compensation
      (vestibulocollic reflex, VCR). The head gain increased significantly at 13-18
      weeks of age as in the OKR case. When the drum and the chair were oscillated
      synchronously (inhibition of VOR, VORINHIB), the compensatory eye gain was
      significantly lower than in the VVOR, indicating suppression of VOR. This effect
      was considerable at 3 weeks. However, VCR was not suppressed but comparable to
      the VVOR condition at all ages studied. In summary, we found that the vestibular
      control of smooth gaze adjustment functions earlier than the visual control. At 2
      months, the visual control improves dramatically and at 3-4 months head
      participation increases considerably. The eye gain in the VORINHIB condition
      could be well predicted by vector addition of the eye position signals in the OKR
      and VVOR conditions.

PMID- 10958524
TI  - Effects of body orientation, load and vibration on sensing position and movement
      at the human elbow joint.
AB  - Experiments were carried out to study the ability of human subjects to match the
      position of their forearms relative to the horizontal. The normal, arms-in-front
      position with the hands aligned and little forward flexion at the shoulder was
      called the reference position. When the arms were rotated to the side, one arm
      was raised, or both arms were raised, matching ability deteriorated compared with
      the reference position, when expressed as an increase in the standard deviation
      of matching errors. It was concluded that particular significance was assigned by
      the brain to the arms-in-front position, with the hands in their normal working
      space. Increases in errors were also observed when the reference arm was made
      weightless or its weight was increased by means of an adjustable load. This
      suggested that lifting the arm against gravity provided additional positional
      information. In a second experiment, dependence of the illusion of muscle
      lengthening evoked by vibration was tested after two different forms of muscle
      conditioning, a co-contraction of elbow muscles with the arm held flexed or with
      it held extended. The speed of the illusory extension of flexor muscles during
      their vibration increased three-fold after flexion conditioning compared with
      extension conditioning. Since after flexion conditioning, muscle spindles in
      flexor muscles are expected to be more sensitive to vibration than after
      extension conditioning, this observation provides additional support for the view
      that muscle spindles make an important contribution to kinaesthesia at the elbow
      joint.

PMID- 10958523
TI  - Molecular regulation of glutamate and GABA transporter proteins by valproic acid
      in rat hippocampus during epileptogenesis.
AB  - Epileptiform discharges and behavioral seizures may be the consequences of the
      presence of either excessive excitation associated with the neurotransmitter
      glutamate or from inadequate inhibitory effects associated with gamma
      aminobutyric acid (GABA). Synaptic effects of these neurotransmitters are
      terminated by the action of transporter proteins that remove these amino acids
      from the synaptic cleft. The glial transporters glutamate-aspartate transporter
      (GLAST) and glutamate transporter-1 (GLT-1), and the neuronal transporter
      excitatory amino acids carrier-1 (EAAC-1) limit excitation initiated by synaptic
      release of glutamate. Transporter proteins GABA transporter-1 (GAT-1) and GABA
      transporter-3 (GAT-3) remove GABA from synaptic regions. To assess the molecular
      effects of the antiepileptic drug valproate, albino rats with chronic,
      spontaneous, recurrent seizures induced by amygdalar injection of FeCl3 were
      treated for 14 days with either valproic acid or with saline as an injection
      control. Regions of the hippocampus were assayed for glutamate and GABA
      transporters by western blot. While epileptogenesis is thought to correlate with
      the downregulation of GLAST and upregulation of EAAC-1, valproate caused an
      increase in the quantity of GLAST protein measured in the hippocampus. Valproate
      treatment decreased GLT-1 in both control and experimental animals in both
      hippocampi. EAAC-1 was unchanged by valproate treatment. GABA transporters GAT-1
      and GAT-3 in the hippocampus were upregulated by FeCl3 injection into the
      amygdala. However, valproate caused the downregulation of these GABA transporters
      in both control and experimental animals. Altered molecular regulation of
      glutamate appears to be critical in the development of sustained, spontaneous
      limbic seizures. Our data suggest that valproate may have unique mechanisms of
      action; specifically, it may affect the removal of glutamate by upregulating
      GLAST and decreasing GABA transport, which could result in increased tissue
      concentrations of GABA.

PMID- 10958526
TI  - Involvement of the human medial cerebellum in long-term habituation of the
      acoustic startle response.
AB  - Animal studies have shown an involvement of the cerebellar vermis in long-term
      habituation of the acoustic startle response, but not in short-term habituation.
      The aim of the present study was to investigate whether short-term and long-term
      habituation of the acoustic startle response are impaired in patients with medial
      cerebellar lesions. Five patients with midline cerebellar lesions due to surgery
      for astrocytoma and ten healthy, age- and sex-matched subjects were studied.
      Subjects received 40 acoustic startle stimuli each day on five successive days.
      Peak amplitudes of the startle response recorded at the orbicularis oculi and the
      sternomastoid muscles were obtained. Data were analyzed for response decrement
      within the training session of one day (short-term habituation) and for a
      decrease in the startle response across the five training days (long-term
      habituation). Short- and long-term habituation of the startle response recorded
      at the sternomastoid muscles could be achieved in controls and in cerebellar
      patients. However, long-term habituation of the blink component of the acoustic
      startle response recorded at the orbicularis oculi muscles was significantly
      impaired in patients with cerebellar lesions compared with control subjects,
      whereas short-term habituation was preserved in both groups. The present findings
      suggest that the medial cerebellum is involved in long-term habituation of the
      blink component of the startle response in humans.

PMID- 10958525
TI  - Regional heterogeneity of dopaminergic deficits in vervet monkey striatum and
      substantia nigra after methamphetamine exposure.
AB  - Methamphetamine (METH)-induced neurotoxicity within the striatum and substantia
      nigra of the vervet monkey was characterized by heterogeneous decreases in
      immunoreactivity (IR) for dopamine system phenotypic markers. Decreases in IR for
      tyrosine hydroxylase (TH), dopamine transporter (DAT), and the vesicular
      monoamine transporter (VMAT2) were observed 1 week after METH HCI (2x2 mg/kg; 24
      h apart). Regional changes throughout the rostrocaudal extent of the striatum
      were characterized by a gradient of neurotoxic effect (lateral greater than
      medial) and the preservation of patches of IR. The decreases in IR in the caudate
      and putamen were greater than those in the nucleus accumbens. The reduced IR in
      the METH-exposed striatum allowed for the visualization of dopamine phenotype
      cell bodies. Within the ventral midbrain, the METH-exposed substantia nigra pars
      compacta (SNc) also showed a heterogeneous loss of IR (lateral greater than
      medial). In contrast, the ventral tegmental area (VTA) showed only minor
      decreases in IR. The magnitude of the decreases in the SNc and VTA subregions
      corresponded to those observed in their respective striatal projection areas,
      suggesting that nigrostriatal neuron subpopulations were differentially reactive
      to METH. The profile of these drug-induced nigrostriatal dopamine system deficits
      resembles aspects of Parkinson's disease pathology and, as such, may provide a
      useful model with which to evaluate neuroprotective and neurorestorative
      strategies.

PMID- 10958527
TI  - Curariform peripheral block of muscular tone selectively increases precentral N30
      somatosensory evoked potentials component. A pharmacological study carried out on
      healthy subjects and parkinsonian syndromes.
AB  - In the present study we investigated whether the precentral component (N30) of
      short somatosensory evoked potentials (SEPs) to median nerve stimulation may be
      modified by peripheral neuromuscular blocking agent in patients affected by
      rigidity. We, therefore, recorded SEPs in nine Parkinson's disease (PD) patients
      and in seven psychotic patients affected by neuroleptic malignant syndrome (NMS),
      all showing severe rigidity. Each patient group was studied before and after the
      placebo, and before and after an atracurium besilate bolus of 0.05 mg/kg, in a
      single recording session. At the time of the test the PD patients had not taken
      any antiparkinsonian therapy for at least 48 h. The same recordings were also
      taken on nine neurologically normal subjects undergoing surgical procedures.
      Atracurium administration produced a remarkable amplitude increase of the major
      precentral component (N30) of SEPs. An atracurium-induced N30 amplitude increase
      was observed in both PD patients (from 2.41 to 4.07 microV) and NMS psychotic
      patients (from 2.03 to 3.97 microV), whereas there was a minor N30 amplitude
      increase in healthy subjects (from 3.53 to 4. 10 microV). The N30 latency was
      unaffected. Amplitude and latency of the major parietal SEPs component (N20) was
      unchanged in the three groups studied. Our results lead to the conclusion that a
      neuromuscular blocking agent is capable of increasing the N30 amplitude in
      patients affected by severe rigidity, exclusively reducing their muscular tone
      without interfering with the central dopaminergic system. Thus, a "peripheral
      gating" of sensory input to the supplementary motor area due to rigidity may play
      a relevant role in producing the N30 amplitude decrease described in patients
      affected by degenerative or pharmacologically induced parkinsonism. The reduction
      of rigidity could be the mechanism by which dopamine may increase the precentral
      N30 amplitude in parkinsonian syndromes.

PMID- 10958528
TI  - Selective enhancement of motoneurone short-term synchrony during an attention
      demanding task.
AB  - Recent experiments on monkeys suggest that attention-related changes in the
      synchronous activity of neurones occur in the motor cortex. In humans, the
      clinical data available suggest that the weak synchronization of the motor unit
      firing observed during voluntary contraction might reflect the activity of the
      motoneurone cortico-spinal afferents. The present study was therefore designed to
      investigate how the synchronous motor-unit activity might depend on the attention
      required in performing a motor task. Twenty-five motor unit pairs were tested in
      the right extensor carpi radialis muscles of five right-handed subjects, who were
      instructed to keep both motor units firing tonically while trying to maintain the
      extension force as constant as possible using visual feedback set either at low
      or high gain. Fifteen motor unit pairs (60%) showed a greater amount of
      synchronous activity, without any consistent changes in the motor unit firing
      rates, when the subjects were monitoring the force at high gain. In addition, the
      mean value and the steadiness of the force did not differ significantly between
      the two tasks. The amplitude of the motor units' contractile force extracted by
      spike-triggered averaging did not change consistently despite the slight increase
      in the synchronous impulse probability observed under the high-gain conditions.
      Changes in synchrony affected slowly contracting, low-threshold motor units as
      well as fast-contracting, high-threshold motor units. The most noteworthy finding
      was that these changes actually focused on a narrow component of the synchronous
      activity (within a period of less than 4 ms) in keeping with the short-term
      synchronization process. This suggests that common inputs, possibly of cortical
      origin, may have contributed more greatly to controlling the motoneurone firing
      pattern in the motor task which required the subjects to pay more attention.

PMID- 10958529
TI  - Inhibition versus facilitation of the reflex responsiveness of identified wrist
      extensor motor units by antagonist flexor afferent inputs in humans.
AB  - The question of whether Ia reciprocal inhibition might depend on the motor task
      and on the type of motor unit activated was investigated in the human extensor
      carpi radialis muscles. Ia reciprocal inhibition induced by stimulating the
      median nerve (conditioning stimulation) was estimated by measuring the changes in
      the firing probability of 37 extensor motor units in response to the radial nerve
      stimulation (100 test stimuli) delivered 1 ms after the conditioning stimulation.
      Six subjects were asked to perform a task consisting of either selectively
      contracting their wrist extensor muscles or co-activating their wrist and finger
      antagonist muscles by clenching their hand around a manipulandum. In the control
      recordings (test stimulation alone), the mean response probability of the 37
      motor units was found to be greater during hand clenching. The motor units were
      identified on the basis of their force thresholds, their macro-potentials, and
      their twitch contraction times. The data obtained in the control recordings were
      consistent with the size principle. In the recordings where the responses were
      conditioned by applying median nerve stimulation, the response probability of the
      motor units with low force thresholds, small macro-potential areas, and long
      twitch contraction times tended to decrease, in line with the presence of Ia
      reciprocal inhibition, whereas the response probability of the motor units with
      higher force thresholds, larger macro-potential areas, and shorter twitch
      contraction times tended to increase. The median nerve stimulation may therefore
      have altered the efficiency with which the extensor Ia inputs recruited the
      homonymous motoneurones in the pool. The flexor group I afferents activated while
      the median nerve was stimulated had inhibitory effects on the slow contracting
      motor units, and facilitatory effects mainly on the fast contracting motor units.
      Both of these effects were stronger during hand clenching, in which the numerous
      cutaneous receptors of the palm and fingertips are liable to be activated.
      Besides their own effects on the excitability of the various types of motor
      units, cutaneous inputs are known to potentiate the Ib interneurones. In
      addition, the effects of the conditioning stimulation were superimposed on the
      tonic activity of the Ia and Ib afferents from the flexor wrist and finger
      muscles. This may explain why both the inhibitory and facilitatory effects of the
      median nerve stimulation were enhanced during hand clenching.

PMID- 10958531
TI  - Vergence provides veridical depth perception from horizontal retinal image
      disparities.
AB  - One useful source of depth information available to the human nervous system is
      present in the horizontal disparities that exist between the two retinal images
      (stereoscopic depth). The relationship between horizontal disparity and depth
      varies with viewing distance so that an interpreting signal is required if
      disparities are to yield useful information. One potentially useful interpreting
      signal is available from ocular vergence. A number of studies have concluded,
      however, that a vergence signal does not provide veridical stereoscopic depth.
      All of these studies required observers to make a range of judgements under
      conditions of uncertainty (often using random dot stimuli) and we suggest that
      the lack of veridicality arose because of a contraction bias: a general tendency
      to bias judgements towards the centre of the range of possible responses. We re
      examined the role of ocular vergence in the maintenance of stereoscopic depth
      constancy for real three-dimensional objects. Our results question the
      conclusions reached by previous studies and suggest that vergence can provide a
      veridical interpretation of stereoscopic depth. Our results indicate that
      horizontal retinal image disparities are not interpreted by a 'higher order'
      signal (i.e. the 'perceived distance' of the fixation point). The results of the
      experiment have significant implications for models of depth processing from
      disparity.

PMID- 10958530
TI  - Areas of operation of interneurons mediating presynaptic inhibition in sacral
      spinal segments.
AB  - Sources of primary afferent depolarization (PAD) of skin afferents in the sural
      (Sur) nerve and of group-II muscle afferents in the posterior biceps and
      semitendinosus (PBST) nerve were compared at several sites, about 2 mm apart,
      within the L7-S2 segments in order to define areas of projection of sacral
      interneurons mediating PAD of these afferents. Just rostral to the pudendal
      nucleus, strong PAD of Sur afferents was evoked by stimulation of skin nerves,
      while stimulation of muscle nerves had only marginal effects. This indicates that
      sacral PAD interneurons co-excited by skin and muscle afferents operate primarily
      within the regions overlying the pudendal nucleus. Furthermore, PAD evoked by
      muscle afferents was weaker over the rostral part of the pudendal nucleus than
      over the caudal part of this nucleus, where hamstring afferents became its main
      source, both in Sur and in PBST group-II afferents. By correlating the relative
      strength of PAD at the levels of the rostral and caudal parts of the pudendal
      nucleus with the previously established input from muscle and cutaneous afferents
      to interneurons at these levels, it is therefore proposed that sacral PAD
      interneurons operate over shorter distances than indicated by previous
      experiments: over either rostral or caudal parts of the pudendal nucleus, i.e.,
      about 2 mm, rather than over the whole length of this nucleus, i.e., 4-5 mm.
      Sacral PAD interneurons may, thus, modulate synaptic transmission to even more
      spatially restricted neuronal populations than previously proposed.

PMID- 10958532
TI  - Eye-hand coordination to visual versus remembered targets.
AB  - It has been suggested that the basal ganglia preferentially contribute to
      movements made to remembered targets, whereas the cerebellum preferentially
      contributes to movements based on visual cues. Thus, it is possible that eye-hand
      coordination may differ in these two types of movement. To examine this issue we
      compared the response characteristics of combined eye and hand movements made
      towards visual versus remembered targets. In addition, the influence of the eye
      movement on the hand movement was investigated by comparing the effects of visual
      fixation in each task. Our results demonstrated that hand movement amplitude was
      greater when the hand movements were produced in isolation versus in combination
      with an eye movement. This was true regardless of whether the movement was made
      to a visual or a remembered target. This suggests that the integration of eye
      position information into the manual motor response occurs at a common neural
      site for both tasks. By contrast, the timing between saccade and hand onsets and
      offsets differed in the two conditions. This is consistent with the idea that the
      timing inherent in eye-hand coordination is the result of separate processing
      within either the basal ganglia or cerebellar systems. Taken together, the
      results from this study demonstrate that certain processes underlying eye-hand
      coordination during movements to visual versus remembered targets share a common
      neural substrate whereas others function independently.

PMID- 10958533
TI  - Clinical and laboratory findings in cases of toxic mastitis in cows in Northern
      Ireland.
AB  - This paper describes the clinical and laboratory findings from 264 cases of toxic
      mastitis in cows in Northern Ireland between October 1995 and May 1997. Nearly
      all the cases occurred during the winter housing period, with 84 per cent
      occurring between November and March inclusive, and 30 per cent in March. Sixty
      per cent of the cases occurred within one month of calving, and 29 per cent
      within four days of calving. The most common clinical signs were lethargy (92 per
      cent), discoloured milk (90 per cent), anorexia (72 per cent), tachypnoea (23 per
      cent), diarrhoea (23 per cent), recumbency (18 per cent) and staggering (15 per
      cent). Severe pyrexia (18 per cent) and clinical dehydration (44 per cent) were
      relatively common findings. Pure growths of Escherichia coli were isolated from
      50 per cent of the milk samples, but 11 per cent yielded no bacterial growth. In
      vitro sensitivity tests indicated that enrofloxacin was effective against 98 per
      cent of the bacteria isolated, and framycetin and amoxycillin/clavulanic acid
      against 91 per cent. Abnormally high blood urea levels were observed in 31 per
      cent of cases, high blood creatinine levels in 42 per cent, and severe leucopenia
      in 56 per cent. Of the cases which were followed up, 14 per cent died, 21 per
      cent were culled early and a further 22 per cent lost milk production from the
      affected quarter.

PMID- 10958534
TI  - Use of the bisphosphonate drug alendronate for palliative management of
      osteosarcoma in two dogs.
AB  - The bisphosphonate drug alendronate was used to suppress bone remodelling and
      tumour osteolysis as a palliative treatment for two dogs with osteosarcoma, one
      of the tibia and one of the maxilla. A spiral fracture associated with the tibial
      tumour healed after it was stabilised with an external skeletal fixator. Both
      dogs remained comfortable and survived for 12 and 10 months respectively after
      diagnosis, despite the fact that neither primary tumour was resected.

PMID- 10958535
TI  - Duration of cross-protection between subtypes A and B avian pneumovirus in
      turkeys.
AB  - The degree and duration of clinical and virological cross-protection between
      avian pneumovirus subtypes A and B were examined in two-week-old pneumovirus
      antibody-free turkeys. The turkeys were inoculated with either a virulent subtype
      A (Belgian isolate A/T6/96), a virulent subtype B (Belgian isolate B/T9/96), an
      attenuated subtype A or an attenuated subtype B, and challenged homologously and
      heterologously with virulent avian pneumovirus two, five and 11 weeks after
      inoculation. Birds inoculated with virulent A or B virus showed typical
      respiratory signs from three to seven days after inoculation. After challenge, no
      clinical signs were observed in any of the groups, and no virus was isolated from
      the turkeys that had been initially inoculated with a virulent strain. Virulent
      virus was recovered from the birds that had been initially inoculated with
      attenuated subtypes and challenged five and/or 11 weeks later with a heterologous
      virulent strain. Birds challenged after five weeks showed a serological booster
      reaction only when they had been inoculated initially with a virulent or
      attenuated subtype B and challenged with subtype A. Seroconversion was observed
      in all the groups challenged after 11 weeks except when they had been inoculated
      initially with attenuated subtype B and challenged with subtype B.

PMID- 10958536
TI  - Chorioptic mange in British Suffolk rams.

PMID- 10958537
TI  - Rhabdomyolysis associated with Escherichia coli gastroenteritis in a cat
      suffering from chronic renal failure.

PMID- 10958538
TI  - Persistent efficacy of topical doramectin and eprinomectin against Ostertagia
      ostertagi and Cooperia oncophora infections in cattle.

PMID- 10958539
TI  - Pet travel scheme.

PMID- 10958540
TI  - RCVS annual retention fee.

PMID- 10958541
TI  - VN training.

PMID- 10958542
TI  - PMWS and PDNS in Great Britain.

PMID- 10958543
TI  - Transmission of anthelmintic-resistant nematodes via hay?

PMID- 10958544
TI  - Congenital joint laxity and dwarfism in calves.

PMID- 10958545
TI  - Relevant factors in multiple shunt failures.

PMID- 10958546
TI  - Radiation-induced tumors of the central nervous system occurring in childhood and
      adolescence. Four unusual lesions in three patients and a review of the
      literature.
AB  - The authors report four very rare radiation-associated tumors (or radiation
      induced tumors; RITs) of the central nervous system (CNS) and review the
      literature on this topic. The purpose of this study was to determine the possible
      relationship between the harmful effects of radiation therapy, the shortest and
      the longest interval between the time of irradiation and the occurrence of the
      secondary tumor, and possible predisposing factors. The tumorigenic effects of
      therapeutic irradiation of the CNS have been mentioned in the literature, but the
      authors' literature search did not disclose either many reports of cases such as
      their own or a satisfactory and concise discussion on the different aspects of
      the late and catastrophic complications of this method of adjunct therapy to the
      CNS. Four rare cases of RIT in three patients are presented: a unique case of
      intradural meningioma of the cervical spine, which was irradiated successfully
      only for the patient to present with a new high-grade cerebral astrocytoma 4
      years later, a paraventricular cavernoma and a fronto-temporo-orbital
      chondrosarcoma. These second RITs became symptomatic in the 17th, 16th and 15th
      years of life, respectively, in these young patients. The primary lesions were
      ependymomas, two in the IV ventricle and one in the left hemisphere. The time
      intervals between radiation and secondary tumor presentation were 14 and 18
      years, 9 years and 28 months, in the order in which these patients presented. All
      the patients survived the second operation except the one with chondrosarcoma,
      who died in spite of repeated surgical interventions and adjunct therapies. It is
      concluded that the development of secondary RITs does not necessarily require a
      very long time interval; that although sarcomas are the most common RITs of the
      CNS in childhood and adolescence, benign and other rare and curable lesions may
      also occur in the field or vicinity of the field of radiation; and that in view
      of the possibility of occurrence of different types of RITs after varying time
      intervals in a single patient, whole-life followup of similar patients is
      mandatory.

PMID- 10958547
TI  - Early diffuse leptomeningeal primitive neuroectodermal tumors can escape
      detection by magnetic resonance imaging.
AB  - Primitive neuroectodermal tumors are easily detected by neuroradiologic imaging,
      as a rule. We report on two patients with early diffuse leptomeningeal primitive
      neuroectodermal tumors which escaped detection by contrast-enhanced magnetic
      resonance imaging.

PMID- 10958548
TI  - Increasing chronic subdural hematoma after endoscopic III ventriculostomy.
AB  - OBJECT: Endoscopic III ventriculostomy (ETV) is an effective and a rather safe
      treatment for noncommunicating hydrocephalus secondary to aqueductal stenosis and
      other obstructive pathologies. Though not devoid of risk, ETV is increasingly
      replacing shunt operations, and it prevents related complications, including
      overdrainage. METHODS: We report a rare case of a large chronic subdural hematoma
      (ChSDH) after ETV in a patient with aqueductal stenosis. Three weeks after he was
      shunted elsewhere, he presented to us with clinical symptoms of intracranial
      hypotension and overdrainage. ETV was performed and the shunt removed
      uneventfully. On routine postoperative MRI a few weeks later, a large ChSDH was
      noted, the patient being totally asymptomatic. Since the ChSDH grew
      significantly, causing a mass effect on the follow-up MRI, it was finally
      drained. Large and increasing ChSDHs have previously been reported secondary to
      overdrainage after shunt placement, but not after ETV. CONCLUSIONS: We conclude
      that though rare, a ChSDH may evolve even after ETV, if there is a substantial
      decrease in previously elevated intracranial pressure.

PMID- 10958549
TI  - Meningiomas of the central nervous system occurring below the age of 17: report
      of 24 cases not associated with neurofibromatosis and review of literature.
AB  - The objective of this work was to gain more insight into the controversial
      characteristics of meningiomas occurring during childhood and adolescence.
      Management of meningiomas is an important field in pediatric neurosurgery. Every
      pediatric neurosurgeon has tried to resolve the problems relating to the clinical
      characteristics, biological behavior and outcome of this interesting and almost
      benign pathology, which rarely occurs in the first two decades of life. The
      records on central nervous system (CNS) tumors held by the two major neurosurgery
      centers of Tehran Medical University and Arad General Hospital were prospectively
      collected during last 15 years. Complete medical records are available for all 24
      cases, and long-term follow-up was achieved 19 patients. All the cases were
      diagnosed and treated after the introduction of computed tomographic (CT)
      scanning. Angiography and magnetic resonance imaging (MRI) were performed as
      complementary studies in some cases. The sample consisted of 13 girls and 11
      boys. The age range at the time of diagnosis varied between 2 and 17 years, with
      a mean of 9.47 and standard deviation of 3.43. Fifteen patients were below 10
      years of age (62.5%), and 9 of them were between 10 and 17 years old (37.5%). The
      most common presenting symptoms, in declining order of frequency, were headache,
      epilepsy and focal neurological deficits. Similar cases associated with
      neurofibromatosis either at the time of presentation with meningioma or during
      the follow-up period were excluded (5 cases). The size of the presenting tumor
      was more than 5 cm in diameter in 17 cases. The locations of the lesions, taken
      as the site of the presumed widest dural base in each case were: spinal, orbital,
      ethmoidal and sphenoethmoidal in 1 case each, petroclival in 2, and tentorial or
      supratentorial in 18 patients. The only predisposing factor in this series of
      childhood meningiomas was whole-axis irradiation for previous malignancy in the
      case presenting with cervical intradural meningioma. There have been no surgical
      deaths, and gross total excision of the lesions was achieved in 21 cases. Tumor
      recurrence was observed during the follow-up period in 6 cases (25%). The follow
      up period varied between 2 and 165 months, with a median interval of 130.2
      months. This series of pediatric CNS meningiomas comprises almost 1.08% of all
      meningiomas operated on by the authors during the last 15 years and it also
      accounts for about 1.1% of all pediatric CNS tumors encountered. This series of
      patients has certain characteristics regarding sex distribution, unusual size,
      peculiar localizations, special histological features and benign clinical
      behavior distinguishing it from other series reported in the literature.

PMID- 10958550
TI  - Cerebellar gliomas in children with NF1: pathology and surgery.
AB  - Cerebellar gliomas associated with NF1 (CGNF1) are rarely reported in the
      literature, and they are considered to be malignant in a high proportion of
      cases. In an attempt to improve the definition of this disease and clarify its
      management, we reviewed our patients with CGNF1 and compared their tumors with
      sporadic cerebellar gliomas (SGC). We operated on six children with CGNF1, all
      but one of whom were asymptomatic. They represented one-tenth of all pediatric
      cerebellar gliomas, and one third of NF1-associated gliomas seen in our
      institution. CGNF1 appeared at a later age than SCG. They are seated near the
      roof of the IV ventricle and are not related to white matter hypersignal
      hamartomas. Most of these tumors showed radiological progression. They were four
      pilocytic astrocytomas, one ganglioglioma, and one malignant astrocytoma. One
      patient had tumor recurrence after 8 years, and the others are still disease
      free. The overall outcome appeared to be better for GCNF1 than for SCG. On
      account of the regular growth, uncertain pathology, and good surgical outcome, we
      advocate systematic resection of these tumors.

PMID- 10958551
TI  - Clinical feature and outcome of pediatric cerebrovascular disease: a
      neurosurgical series.
AB  - To investigate the clinical features and surgical outcome of pediatric
      cerebrovascular disease (CVD), we retrospectively reviewed 280 children (up to 15
      years of age) who underwent neurosurgical procedures for CVD between 1979 and
      1998. Open surgery (n=448), endovascular procedures (n=22), and stereotactic
      radiosurgery (n=14) were the main neurosurgical procedures adopted. Clinical
      features and surgical outcomes were described according to the etiology of the
      CVD and the number of years of management. The mean duration of follow-up was 34
      months. The mean age was 7.1 years, and the male-to-female ratio was 1.2:1. The
      most frequent CVD was moyamoya disease (62%). The surgical mortality related to
      CVD was 0.7%. Eighty-seven percent had Karnofsky Performance Scale scores of more
      than 70. We demonstrate increasing detection rates and improving outcomes in
      recent years. The clinical course in this study shows that recovery from CVD in
      children is good after neurosurgical procedures.

PMID- 10958552
TI  - Long-term external drainage for subdural collections in infants.
AB  - The treatment of subdural collections in infants remains controversial. In order
      to evaluate the treatment guidelines that we developed on the basis of our
      earlier experience, we have reviewed the results obtained in 31 consecutive
      infants with symptomatic chronic and subacute subdural collections treated with
      external drainage. Using our guidelines for removal of the drains, there was only
      a very low rate of permanent shunting (4/31), with a low complication rate and
      good clinical results. However, the long period of external drainage, and
      therefore of hospitalization, might make if general application of these
      guidelines problematic.

PMID- 10958553
TI  - Complications of subduroperitoneal shunting.
AB  - OBJECTS: Subduroperitoneal (SP) shunts have been widely used in the management of
      pediatric subdural fluid collections. METHODS: We retrospectively reviewed the
      complications of SP shunting in 73 boys and 24 girls, who ranged in age from 1 to
      180 months (median 7 months). Subdural fluid collection was bilateral in 75 and
      unilateral in 22 patients. The most common complication was shunt obstruction (13
      patients). Shunt migration was seen in 8 patients. Migration occurred only with
      unishunts without a reservoir and with peritoneal catheters. However, the shunts
      with a reservoir or flushing valve led to skin necrosis in 4 patients (P=0.003).
      Unilateral drainage though bilateral collections were present, infection, bowel
      perforation, and ileus occurred in 5, 4, 1 and 1 patients respectively.
      CONCLUSIONS: These SP shunt complications, some of which are avoidable, should be
      kept in mind.

PMID- 10958554
TI  - Frontal head posture in shunt-treated hydrocephalic patients.
AB  - OBJECTS: The aim of this study was to evaluate frontal head posture in shunt
      treated hydrocephalic patients and its relation to the sidedness of the shunt
      device. METHODS: Natural head position and frontal cephalograms of 55 shunt
      treated Finnish hydrocephalic patients and 33 healthy Finnish subjects were
      analysed using a computerised digitising program (X-METRIX). The following
      reference angles were used: ORB/HOR, indicating the head position related to the
      true horizontal; CER/VER, indicating the cervical position related to the true
      vertical; and CER/CR, indicating the craniocervical position. CONCLUSIONS: The
      results showed an increased skewness of the head in the shunt-treated subjects,
      which was not related to the shunt side.

PMID- 10958555
TI  - Outcome analysis of endoscopic III ventriculostomy.
AB  - A retrospective chart review was performed on 54 patients who had undergone
      endoscopic III ventriculostomy (E3V) in the past 6 years. Patient charts were
      reviewed to establish age at the time of operation, sex, preoperative diagnosis,
      preoperative shunt procedures, success or failure of the E3V, duration of
      success, and complications. Success of an E3V was determined by the resolution of
      preoperative symptoms and avoidance of a CSF shunt. The most recent clinic visit
      with adequate documentation of signs and symptoms of hydrocephalus was used as
      the last date of follow-up. The overall success rate was 74%. Children over the
      age of 3 years with an acquired CSF obstruction had a significantly greater
      probability of successful treatment (P=0.05). Younger children, especially those
      with hydrocephalus attributable to obstruction of the arachnoid villi, as in
      intraventricular hemorrhage (IVH), were less likely to benefit from E3V.

PMID- 10958556
TI  - Unusual clinical manifestations of disturbed CSF dynamics in hydrocephalic
      children.
AB  - OBJECTS: Clinical symptoms and signs of increased intracranial pressure (ICP) may
      be nonspecific and unreliable, or even entirely absent, in hydrocephalic infants
      and children. Even with a radiological examination, it is often difficult to
      distinguish between "arrested hydrocephalus" and slowly progressive hydrocephalus
      requiring treatment. METHODS: We present two cases with unusual and initially
      misleading clinical manifestations of increased ICP. In both cases, the disturbed
      cerebrospinal fluid (CSF) dynamics, i.e. raised ICP, were not recognised until
      demonstrated by a long-term ICP monitoring. In a 5-month-old boy with normal head
      circumference and normal psychomotor development, the sudden onset of episodes of
      torticollis and screaming were the only symptoms. No pathology underlying the
      developing hydrocephalus and the raised ICP could be established, but the boy's
      condition improved after a shunt operation. In the other case, symptoms and signs
      consisted primarily in a slowly progressive dilatation of the facial veins with
      onset at the age of 2-3 years. As the girl also presented a congenital
      subvalvular aortic stenosis, the venous congestion was initially thought to
      reflect a vena cava superior syndrome. Further radiological examinations,
      however, revealed an extensive sinus thrombosis underlying the raised ICP. The
      girl underwent shunt insertion, and the venous congestion was reduced.
      CONCLUSIONS: The cases illustrate that though clinical and radiological findings
      may be very doubtful, or unusual for increased ICP, direct diagnostic long-term
      ICP monitoring should always be contemplated. Only ICP monitoring can reveal with
      certainty whether disturbed CSF dynamics are involved, requiring a CSF diverting
      operation to treat and stabilise the condition.

PMID- 10958557
TI  - The dynamic infusion test in rats.
AB  - Although the hydrocephalic H-Tx rat is a widely used model, data on the
      cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or - as the
      pressure volume index (PVI) - not available. We used hydrocephalic and
      nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited
      hydrocephalus, for the evaluation of such data. In addition, a new, simple
      mathematical algorithm ("dynamic infusion test"), which has not formerly been
      used in animal experiments, was used as a pathophysiological model of CSF
      dynamics. Compared with classical methods for evaluation of these data, the
      dynamic infusion test gives a deeper insight into the relation between ICP and
      CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic
      rats was at least twice that in nonhydrocephalic rats. The PVI measured was
      similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than
      the values reported in the literature. This may be attributable to the fact that
      the classically used bolus test, in contrast to the "dynamic infusion test", is
      representative only for the CSF compartment which is directly exposed to the
      bolus application.

PMID- 10958558
TI  - Secondary tethered cord syndrome in spinal dysraphism.
AB  - Secondary tethered cord syndrome following initial repair for spinal dysraphism
      is an important area of interest. In this study, 32 cases with spinal dysraphism
      in the lumbosacral region were enrolled, in whom radical repair with autologous
      material had been carried out in the early stage soon after birth. During the
      follow-up period of up to 19 years 10 months, surgery was considered to be
      indicated in 2 of the 8 lipomeningocele cases and in 6 of the 24 meningocele and
      meningomyelocele cases, because of the presence of tethered cord syndrome 4-19
      years after the primary operation. In all 8 of these cases, MR imaging
      demonstrated tethered spinal cord in the form of low conus medullaris. In 6 of
      the 8 operated cases surgery was followed by improvement of the spinal
      neurological deterioration. According to our experience, early untethering for
      secondary tethered cord syndrome is essential. In addition, since the
      complications of Silastic duraplasty at untethering were all minor and the
      operative outcome was satisfactory, the use of silicone rubber sheeting as a
      dural substitute might be recommended to prevent adhesion of the spinal cord.

PMID- 10958559
TI  - Infection-resistant nonleachable materials for urologic devices.
AB  - Bacterial colonization is the primary clinical problem faced by the surgeon and
      medical device innovator. Despite the absence of effective systemic treatment,
      medical implants and devices have been deployed with increasing success over the
      past five decades. Infection-resistant materials (IRMs) are a relatively recent
      addition to the science of implant and device development. The first IRM utilized
      leachable antimicrobial agents. Nonleachable technologies are being developed,
      some of which have the potential to make organ replacement even more successful
      in the future.

PMID- 10958560
TI  - Role of percutaneous urinary diversion in malignant and benign obstructive
      uropathy.
AB  - OBJECTIVES: We evaluated the feasibility and effectiveness of percutaneous
      urinary diversion in patients with obstructive uropathy. PATIENTS AND METHODS: A
      total of 206 percutaneous nephrostomies (PCNs) (right-sided in 54, left in 56,
      and bilateral in 48) were performed in 102 male and 57 female patients 18 to 94
      years old. In 125 patients, malignancy was the underlying cause of the
      obstruction and in 30, benign disease. In four patients, the cause remained
      unknown. In most patients (N = 154), the access was guided with both ultrasound
      and fluoroscopy. RESULTS: Percutaneous nephrostomy was successful in 158 patients
      (99%). Antegrade ureteral stenting was attempted in 48 patients with a success
      rate of 81%. Fifteen days postprocedure, the mean urea and creatinine
      concentrations had declined from 160.8 mg/mL to 63 mg/mL and from 6.9 mg/dL to
      2.2 mg/dL, respectively. In 66% of the patients, renal function returned to
      normal. In 28%, it improved with no need for hemodialysis, while in 6%, there was
      no improvement. Advanced age and prostate cancer were negative predictive factors
      for the improvement of renal function, whereas the BUN and creatinine
      concentrations before the procedure and performance of unilateral v bilateral
      nephrostomies were not. We did not have severe complications. Three patients
      received transfusions, and in one patient, a urinoma was drained percutaneously.
      Patients with malignancy had a median survival of 227 days. CONCLUSION:
      Percutaneous urinary diversion under radiologic guidance is a safe and effective
      procedure for patients with obstructive uropathy.

PMID- 10958561
TI  - Metastatic renal cell cancer after laparoscopic radical nephrectomy: long-term
      follow-up.
AB  - OBJECTIVE: To assess the risk of metastatic disease in longer-term follow-up of
      patients undergoing laparoscopic radical nephrectomy with morcellation for renal
      cell carcinoma (RCC). PATIENTS AND METHODS: We present the findings at follow-up
      at 13.5 to 70 months (mean 33.4 months) of 57 previously reported patients.
      Three, all of whom initially had clinical stage N0M0 disease, were found to have
      metastases. One, who had a clinical stage T3 grade III/IV tumor, developed an
      asymptomatic recurrence in the renal fossa with associated chest metastasis 14
      months postoperatively. The second, who had a clinical stage T2 grade II/IV
      tumor, developed painful bony lesions and a chest metastasis 20 months
      postoperatively. The third patient, with a clinical stage T3 grade IV/IV tumor,
      was found to have a solitary port-side abdominal-wall recurrence with no other
      evidence of metastatic disease at 25 months. CONCLUSIONS: Longer-term follow-up
      has demonstrated a 5% (3/57) rate of metastases after laparoscopic radical
      nephrectomy. In two of these patients, the course was consistent with the natural
      history of RCC; however, the third had a port-site recurrence. Thus, it behooves
      us to be meticulous with our technique and to follow patients closely after
      laparoscopic nephrectomy. Several suggestions are made to reduce the likelihood
      of port-site recurrence.

PMID- 10958562
TI  - Pediatric retroperitoneoscopic nephrectomy.
AB  - The endoscopic retroperitoneal (retroperitoneoscopic) approach to extirpative
      intervention for benign renal disease is increasingly popular. We describe
      several modifications of this approach, including the use of prone positioning
      and 2-mm instruments, that may improve the safety and efficacy of the technique
      in children. These modifications provide unobstructed views of the kidney and
      renal hilum and facilitate dissection in a small working space.

PMID- 10958563
TI  - Minipercutaneous nephrolithotomy.
AB  - PURPOSE: To evaluate the safety and efficacy of a minipercutaneous
      nephrolithotomy procedure (mini-PCNL) through a 20F sheath. PATIENTS AND METHODS:
      Twenty-one patients underwent a mini-PCNL from October 1997 to October 1999. The
      mean number of calculi was 1.8 (range 1-9). The mean cross-sectional area of the
      stone burden was 2.8 cm2 (range 0.72-6.5 cm2). Nephrostomy tract dilation was
      performed with an 18F Cook Omega or Pursuit balloon dilation catheter (6-mm
      diameter, 10-cm length; 12 or 14 atm, respectively), and a 20F nephrostomy sheath
      was advanced over the inflated balloon. RESULTS: The mean operative time was 54
      minutes. The mean decrease in hematocrit was 3.4%, and no patient required a
      blood transfusion. The mean percutaneous tube duration was 22 hours. The mean
      hospital stay was 1.1 days. The single-procedure stone-free rate was 90%. Two
      patients underwent successful SWL of residual middle-caliceal calculi that could
      not be accessed through the existing tract. There were no major complications,
      but there was one episode of prolonged fever secondary to atelectasis. Five
      patients remain free of radiographic or symptomatic recurrence after antegrade
      endopyelotomy for ureteropelvic junction obstruction after a mean of 11 months'
      follow-up. CONCLUSIONS: By using a 20F sheath rather than the traditional 30F
      sheath, we decreased the volume of renal parenchyma that is dilated by 56%. This
      change appears to decrease perioperative bleeding and pain as well as parenchymal
      scarring.

PMID- 10958564
TI  - Cystolitholapaxy versus cystolithotomy in children.
AB  - BACKGROUND: Primary vesical stones are common in children in developing
      countries. Cystolithotomy is the traditional treatment, but a percutaneous
      approach has been advocated. PATIENTS AND METHODS: Between January 1992 and March
      1997, 52 male children with primary vesical stones were treated at our center.
      The patients were stratified retrospectively into two groups according to the
      procedure of stone removal. Group I (25 patients) were children who underwent
      open cystolithotomy, and group II (27 patients) were those who had endourologic
      treatment either by the transurethral route (11 children) or via suprapubic
      approached (16). The mean age at the time of diagnosis was 3.6 +/- 2.1 years. The
      stone size ranged from 0.7 to 2 cm (mean 1.2 +/- 0.7 cm). RESULTS: In all cases,
      the stones were removed successfully. The operative time was similar in the two
      groups. The hospital stay was significantly less after endourologic procedures
      than after open surgery (P < 0.05). In Group I, one patient had a small
      intestinal injury, and in Group II, one patient had urethral rupture and
      extravasation during transurethral cystolitholapaxy. There were no early or late
      complications in Group I. However, in Group II, 4 patients (15%) developed early
      and late complications. Early morbidity was in the form of persistent leakage of
      urine from the suprapubic site in one patient and acute abdomen from the
      peritoneal urine leakage in another two patients who had the same approach. A
      stricture of the bulbous urethra was seen in one patient 1 year after
      transurethral stone disintegration. CONCLUSION: In spite of the improvement of
      endourologic instruments, open surgical removal of primary vesical stones in boys
      is still the mainstay of therapy.

PMID- 10958565
TI  - Laparoscopic adrenalectomy for pheochromocytoma: comparison with open
      adrenalectomy and comparison of laparoscopic surgery for pheochromocytoma versus
      other adrenal tumors.
AB  - OBJECTIVE: To compare the efficacy of laparoscopic adrenalectomy for
      pheochromocytoma with that of conventional open adrenalectomy for
      pheochromocytoma and laparoscopic surgery for other adrenal tumors. PATIENTS AND
      METHODS: Fifty-four patients with adrenal tumors, including 10 cases of
      pheochromocytoma, 18 cases of Cushing's syndrome, 20 cases of primary
      aldosteronism, and 6 cases of nonfunctioning tumors, were evaluated. A historical
      group of 7 consecutive patients who underwent conventional open adrenalectomy for
      pheochromocytoma was also studied. RESULTS: Laparoscopic adrenalectomy for
      pheochromocytoma was successful in 9 of the 10 patients. There was no difference
      in tumor size, operation time, estimated blood loss, or occurrence of
      hypertensive episodes during surgery between patients treated with laparoscopic
      procedures and those treated with open surgery. However, the number of days to
      first postoperative oral feeding and first ambulation, length of hospitalization,
      and number of patients requiring parenteral analgesics were significantly smaller
      after laparoscopic surgery than after open surgery. There was no significant
      difference in operation time, estimated blood loss, incidence of intraoperative
      complications, or postoperative recovery between patients who underwent
      laparoscopic adrenalectomy for pheochromocytoma and those who underwent
      laparoscopic surgery for other adrenal lesions. CONCLUSIONS: Laparoscopic
      adrenalectomy does not increase the specific risks associated with surgery for
      pheochromocytoma. It is a minimally invasive alternative to conventional open
      adrenalectomy.

PMID- 10958566
TI  - Laparoscopic nephrectomy for nonfunctioning tuberculous kidney.
AB  - BACKGROUND AND PURPOSE: Although laparoscopic nephrectomy for benign renal
      disease has been widely accepted, use of the operation for tubercular
      pyelonephritic kidney is relatively contraindicated because of difficulties in
      dissecting the dense fibrotic adhesions and the risk of spillage of caseous
      materials with subsequent dissemination of the disease. However, with the
      accumulation of experience, laparoscopic surgery is expanding its applications.
      In this study, we tried to evaluate the efficacy and safety of the laparoscopic
      nephrectomy for renal tuberculosis. PATIENTS AND METHODS: At three centers, 13
      laparoscopic nephrectomies were performed between April 1996 and March 1999. The
      patients consisted of eight men and five women with a mean age of 44.8 years
      (range 37-51 years). All patients had known renal tuberculosis with a
      nonfunctioning kidney and underwent nephrectomy after at least 3 months of
      chemotherapy with four antituberculous drugs. Nine patients underwent the
      transperitoneal approach and four patients, the retroperitoneal approach. The
      follow-up was from 2 to 35 months with a mean of 15.8 months. RESULTS: Kidneys
      were removed laparoscopically in 12 patients (92%). The mean operative time was
      268 minutes (range 190-500 minutes), and the mean estimated blood loss was 227
      mL. Although there had been some difficulties releasing the adhesions, no
      significant intraoperative and postoperative complications were observed.
      Conversion to open surgery was needed in only one patient. The mean hospital stay
      was 4 days, and the patients returned to normal activity within 10 days. Neither
      local recurrence nor distant dissemination of the disease was observed during the
      follow-up period. CONCLUSION: Laparoscopic nephrectomy for renal tuberculosis was
      safe and effective with minor complications. Therefore, tuberculosis should not
      be a contraindication to a laparoscopic approach.

PMID- 10958567
TI  - Successful management of a large xanthine calculus by percutaneous
      nephrolithotomy after failed SWL in a 5-year-old boy.
AB  - A 5-year-old child with a xanthine calculus resistant to SWL was made stone free
      by percutaneous ultrasonic lithotripsy.

PMID- 10958568
TI  - Nephroenteric fistula treated with fulguration of the fistulous tract.
AB  - We report the management of a nephroenteric fistula with percutaneous fulguration
      in a patient with recurrent pyelonephritis and urolithiasis. A nephrostogram at 6
      weeks and retrograde pyelogram at 18 weeks after fulguration showed no evidence
      of a recurrent fistula. We believe this to be the first reported case of a
      nephroenteric fistula treated successfully with fulguration.

PMID- 10958569
TI  - Ureteral dilation using a tapered dilator: a cost-effective approach.
AB  - BACKGROUND AND PURPOSE: The 6/12 AQ hydrophilically coated tapered dilator is a
      newly developed device for ureteral dilation prior to rigid and flexible
      ureteroscopy. PATIENTS AND METHODS: To evaluate the efficacy, safety, and cost
      effectiveness of this device, it was used to gain ureteral access in 80
      consecutive patients undergoing ureteroscopy for diagnostic purposes, stone
      treatment, or stricture dilation. RESULTS: In all 80 cases, the ureteral orifice
      and intramural ureter were dilated successfully. One complication occurred: an
      embedded stone was extruded through the ureteral wall. Each dilation procedure
      using the 6/12 AQ tapered dilator costs 20% of a balloon dilation, a saving of
      approximately $764 per dilation. CONCLUSION: Ureteral dilation with the 6/12 AQ
      tapered dilator is a safe, effective, and inexpensive alternative to traditional
      dilation techniques.

PMID- 10958570
TI  - Chemolysis of artificial cystine stones (BON(N)-STONES) in vitro using a new
      dissolution device: first results.
AB  - BACKGROUND AND PURPOSE: The treatment of cystine stones is a clinical problem.
      This in vitro study was performed to establish an experimental system that
      enables standardized and reproducible investigations on chemolysis of cystine
      stones to look for an improvement of dissolution strategies. MATERIALS AND
      METHODS: Artificial spherical stones made of cystine (BON(N)-STONES) with a
      diameter of 0.9 cm were used. A new dissolution device was developed simulating
      the physiological conditions in the upper urinary tract with computer-assisted
      online measurement of data. For chemolysis of artificial cystine stones,
      different solvents (artificial urine, physiologic sodium chloride solution, 2 %
      acetylcysteine, 8.4 % sodium bicarbonate solution, THAM, and combinations) were
      used. RESULTS: Chemolysis is an effective tool in the management of cystine stone
      disease. Statistical analysis showed significant differences (p < or = 0.05) for
      all solutions compared with artificial urine alone. A combination of THAM at pH
      10 with acetylcysteine (2%) showed a 48-fold stronger ability to dissolve cystine
      calculi than did artificial urine. CONCLUSION: By performing standardized in
      vitro investigations, new basics to improve the dissolution of cystine stones
      have been developed. It is recommended to use artificial stones made of cystine
      and a dissolution device simulating physiological conditions for investigations
      on chemolysis in the future.

PMID- 10958571
TI  - Usefulness of diagnosis by the urethroscopy under anesthesia and effect of
      transurethral electrocoagulation in symptomatic female urethral diverticula.
AB  - OBJECTIVE: We report accurate diagnosis and simple treatment of female urethral
      diverticula. PATIENTS AND METHODS: When routine urologic evaluation suggested a
      urethral diverticulum, urethroscopy was performed with the patient under
      anesthesia with palpation by an intravaginal finger and transurethral
      catheterization to seek the orifice of the lesion. When a diverticulum was
      detected, transurethral electrocoagulation was performed regardless of the lesion
      size. RESULTS: Urethral diverticula were detected in 18 of 30 women examined
      (60%), with the maximum size being that of the tip of the little finger (about 10
      mm in diameter). Transurethral electrocoagulation was performed. The
      postoperative course was uneventful in all patients, who were discharged from the
      hospital a day after surgery. CONCLUSIONS: Careful urethroscopy under anesthesia
      is a useful diagnostic tool, and transurethral electrocoagulation may be one of
      the best first choices of treatment for female urethral diverticula.

PMID- 10958572
TI  - Histologic effects of holmium:YAG laser resection versus transurethral resection
      of the prostate.
AB  - BACKGROUND AND PURPOSE: Holmium laser resection (HoLRP) is an effective surgical
      alternative to transurethral resection of the prostate (TURP). We investigated
      whether an adequate histologic diagnosis could be made from HoLRP tissue
      specimens. PATIENTS AND METHODS: A series of 120 patients were randomized to TURP
      (N = 59) or HoLRP (N = 61). Each histologic specimen was reviewed by a single
      pathologist, who was blinded to the treatment. Weight of tissue, histologic
      diagnosis, and degree of thermal artifact were assessed. Thermal damage was
      graded as follows: 1 = no significant thermal injury; 2 = <25% of the tissue
      damaged (minimal); 3 = 25% to 80% of the tissue damaged (moderate); and 4 = >80%
      of the tissue damaged, with loss of prostatic architecture (extensive). RESULTS:
      The mean weight of the TURP and HoLRP specimens was 15.6 g and 9.6 g,
      respectively. The mean grade of thermal artifact for the TURP group was 1.8 and
      for the HoLRP group 2.6. Of the HoLRP specimens, 56 (92%) were grade < or = 3. Of
      the entire series of 120 specimens, 5 contained malignant tissue, all of which
      were from the TURP group. Four of these specimens were adenocarcinoma of the
      prostate, whereas the other was a transitional-cell carcinoma. Of the four
      specimens that contained prostate cancer, two were stage pTla tumors.
      CONCLUSIONS: Although identifiable prostatic architecture was maintained in the
      majority of histologic specimens from the HoLRP group, the tissue quality was
      inferior to that of TURP. There was significantly more vaporization and
      subsequent tissue loss with HoLRP, and the thermal damage to tissue was greater.

PMID- 10958573
TI  - Re: controversial cases in endourology: an 18-year-old man with 2-month hisotry
      of left flank pain (J Endourol 2000;14:233-237).

PMID- 10958574
TI  - Antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in
      Istanbul.

PMID- 10958575
TI  - The relationship between resistance in bacteria and antibiotic use in neurology
      and haematology units.

PMID- 10958576
TI  - Negative correlates of computer game play in adolescents.
AB  - There is some concern that playing computer games may be associated with social
      isolation, lowered self-esteem, and aggression among adolescents. Measures of
      these variables were included in a questionnaire completed by 204 year eight
      students at a North London comprehensive school. Principal components analysis of
      a scale to assess needs fulfilled by game play provided some support for the
      notion of 'electronic friendship' among boys, but there was no evidence that game
      play leads to social isolation. Play was not linked to self-esteem in girls, but
      a negative relationship was obtained between self-esteem and frequency of play in
      boys. However, self-esteem was not associated with total exposure to game play.
      Aggression scores were not related to the number of games with aggressive content
      named among three favourite games, but they were positively correlated with total
      exposure to game play. A multiple regression analysis revealed that sex and total
      game play exposure each accounted for a significant but small amount of the
      variance in aggression scores. The positive correlation between playing computer
      games and aggression provides some justification for further investigation of the
      causal hypothesis, and possible methodologies are discussed.

PMID- 10958577
TI  - Learning strategies, learning anxiety and knowledge acquisition.
AB  - In a study of adult technical trainees, it was found that four reported learning
      strategies were significantly associated with learning gain: Rehearsal,
      Interpersonal Help-seeking, Emotion Control and Motivation Control. However, all
      those associations were negative. A prior measure of learning anxiety (but not
      learning ability or learning motivation) was shown to account for that pattern,
      and several learning strategies and learning anxiety were found to interact in
      predicting knowledge change: associations between a strategy and learning were
      more positive for less anxious individuals. Research into learning strategies
      needs to examine additional variables (such as anxiety), and to look beyond the
      school and college settings typically investigated.

PMID- 10958578
TI  - Wanting to have vs. wanting to be: the effect of perceived instrumentality on
      goal orientation.
AB  - Two theories of motivation relevant to classroom learning result in conflicting
      recommendations for enhancing motivation and performance. The goal theory
      stresses only that stimulating an individual's natural curiosity will increase
      motivation. This theory relies on the distinction between intrinsic and extrinsic
      motivation. Future time perspective theory stresses the importance of the
      personal future for motivation and learning and the utility of what is learned
      for the future. A series of studies investigated the role of three types of
      perceived instrumentality of a present task for an individual's goal orientation.
      Eighty-one adults and 229 high school students participated in three studies.
      They had to think of three actions they were regularly involved in during their
      daily life (Studies 1 and 2), or three courses they took (Study 3), corresponding
      to the three types of instrumentality. Afterwards, they responded to a
      questionnaire that assessed goal orientation in those three actions. Results
      suggested that stressing the personal future consequences of tasks, even when
      these were extrinsic, enhanced task orientation and decreased performance
      orientation, both in daily life and in study contexts, as predicted by future
      time perspective theory.

PMID- 10958579
TI  - Quantity and quality of musical practice as predictors of performance quality.
AB  - Twenty-two pianists, classified into four levels of skill, were asked to learn
      and memorize an assigned composition by J. S. Bach (different for each level).
      All practice was recorded on cassette tape. At the end of the learning process,
      the pianists performed their composition in a recital setting. The resulting
      performances were evaluated by three experienced piano teachers. From the
      cassette tapes, values for the quantity of practice were obtained. These values
      were compared across all four levels of skill and examined to reveal whether they
      were related to quality of performance. The analyses indicate that the standard
      deviations of the amount of time spent in each practice session increased
      systematically with level of skill and that pianists at higher levels spent more
      time in each practice session. Quantity of practice, however, was not
      significantly related to quality of performance. Rather, pianists who employed
      longer practice segments by the middle stage of practice produced better musical,
      communicative and technical performances. These findings stand in defiance of the
      argument that quantity of practice is the fundamental determinant of the quality
      of performance. Instead, they suggest that the content and quality of an
      individual's practice must be examined when investigating the determinants of
      musical skill.

PMID- 10958580
TI  - The 'gender gap' in final examination results at Oxford University.
AB  - A lower proportion of women than men obtain first class degrees at British
      universities (the so-called gender gap). At Oxford University, this difference is
      not seen in all degree subjects but is found both in some Arts and in some
      Science subjects. We have used a questionnaire administered under supervision to
      undergraduates 2 to 3 months before their final examination to assess factors
      which might be expected to affect examination performance. These included
      measures of verbal and non-verbal reasoning (Alice Heim AH6 test), self-esteem,
      motivation, responses to stresses of examinations and of personal relationships,
      happiness, risk-taking and working patterns. We have also obtained a detailed
      breakdown of the marks the students were given in the examination. Women scored
      higher on negative emotions while men scored higher on self-esteem, their
      perception of their own academic efficacy and on risk-taking strategies, but none
      of these factors predicted outcome. Verbal reasoning ability did predict outcome
      but there was no gender difference. Hence, it is concluded that the gender gap is
      not due to any of these individual differences and is more likely to be related
      to the nature of the academic assessment system.

PMID- 10958581
TI  - Individual differences in road crossing ability in young children and adults.
AB  - Young children are more at risk of traffic pedestrian accidents than adults.
      Previous experiments have failed to show large differences between adults and
      children in crossing behaviour. The reasons for this are not clear, but it could
      be that some children are more at risk than others, because of individual
      differences. These differences have been difficult to investigate in the past.
      This paper examines a double video technique developed to solve the problems. Two
      groups of participants, children and adults (mean age 7 years 2 months and 20
      years 6 months respectively), were presented with the video and asked to indicate
      by pressing a button when they would choose to cross the road. Variables measured
      included the total number of crossings made and the percentage of those that were
      safe, number of missed opportunities and unsafe gaps chosen, the mean starting
      delay and gap size chosen, and the correlation between the delay and the gap
      chosen for each individual. Results showed that, although there were large and
      significant differences between adults and children on total crossings,
      percentage safe crossings, mean starting delay and gap size chosen, the structure
      of the road crossing behaviour was very similar. Children make decisions in the
      same way as adults, but are less good at it. There were large individual
      differences, suggesting that some children were more at risk than others, with
      possible factors being impulsivity and fine motor coordination. It is suggested
      that the video technique may, with some refinements, make a useful tool to screen
      children at risk and to use in remedial training.

PMID- 10958582
TI  - Closed-circuit television: how effective an identification aid?
AB  - Two experiments simulated identification of suspects from CCTV recordings: Expt 1
      simulated identification from whole body shots while Expt 2 showed close-up
      pictures of targets' faces. The results are consistent with those of Bruce el al.
      (1999) and Kemp, Towell, and Pike (1997) in showing surprisingly high rates of
      error in person identification from CCTV material. In Expt 1, participants (N =
      80) searched for a suspicious incident in a 25-minute surveillance film which was
      shown either in colour or monochrome. They then attempted to describe and
      identify the persons involved. Accuracy of identification was just 15% from
      memory with a 60% false alarm rate. When judgments were made with access to a
      still frame image of the target, accuracy rose to 30%, with a 65% false alarm
      rate. Colour did not improve identification, but did prompt more description of
      the targets' clothing. In Expt 2, participants (N = 80) observed video-clips
      which included close-up pictures, of four targets before identifying each in
      target present or absent arrays. Identification errors were lower on this
      occasion, averaging 21% when judgements were made from memory and 13% with
      continuous reference to the recording. The theoretical and practical implications
      of these findings are discussed.

PMID- 10958583
TI  - Factor structure of the everyday memory questionnaire.
AB  - Although the Everyday Memory Questionnaire (EMQ) has been used in numerous
      studies, no factor structure has vet been obtained from a reasonably large sample
      of non-clinical participants. The 28-item revised version of the EMQ was
      administered to 277 undergraduate students. Analysis showed five clear factors:
      retrieval, task monitoring, conversational monitoring, spatial memory, and memory
      for activities. In general, the factors appeared to reflect underlying memory
      processes rather than just similarities among test items, which suggested that
      using and developing tests of this kind might provide a means of studying the
      diversity of everyday memory phenomena in a unified fashion that would complement
      laboratory research. Issues about the nature of 'absent-mindedness' and the
      relationship between prospective and retrospective memory were discussed.
      Understanding the factor structure of the EMQ should also be useful in clinical
      applications of the test.

PMID- 10958584
TI  - So concepts aren't definitions, but do they have necessary or sufficient
      features?
AB  - Rips (1989) is one of the most widely cited demonstrations of the relevance of
      critical features in conceptual structure. A critical feature will impose
      constraints on how an object is classified, regardless of other factors, such as
      overall similarity. We review and clarify critical features proposals in terms of
      whether an assumption is being made about necessary features, sufficient
      features, or both (i.e. a definition). On the basis of this, we scrutinize Rips'
      investigation and present our own empirical re-evaluation of this work. The
      results reported here do not support any strong view of necessary or sufficient
      features.

PMID- 10958585
TI  - Fatal illnesses associated with a new world arenavirus--California, 1999-2000.
AB  - The California Department of Health Services (CDHS) and the University of Texas
      Medical Branch (UTMB) recently identified evidence of infection with an
      arenavirus in three patients hospitalized with similar fatal illnesses. This
      report summarizes the investigation of these cases.

PMID- 10958586
TI  - State-specific prevalence of disability among adults--11 states and the District
      of Columbia, 1998.
AB  - Disability is a large public health problem in the United States (1), affecting
      an estimated 54 million persons who report disabling conditions (2). One of the
      national health goals for 2010 is to eliminate health disparities among different
      segments of the population, including among persons with disabilities (3).
      Although the development and implementation of public health policy and services
      relating to disability would be aided by public health surveillance (4), the lack
      of a brief case definition of disability limits efforts to obtain state-level
      prevalence to define the magnitude of disability. To assess state-level
      prevalence based on uniform criteria, CDC analyzed data from the Disability
      Module of the 1998 Behavioral Risk Factor Surveillance System (BRFSS). This
      report summarizes the results of the analyses, which indicated an overall
      prevalence consistent with national surveys and demonstrated wide variation in
      disability prevalence in states.

PMID- 10958587
TI  - Update: West Nile virus activity--Northeastern United States, January-August 7,
      2000.
AB  - Surveillance programs initiated in response to the 1999 West Nile virus (WNV)
      outbreak have detected increased transmission in the northeastern United States
      (1). Seventeen states along the Atlantic and gulf coasts, New York City (NYC),
      and Washington, D.C., have conducted WNV surveillance and are reporting to CDC
      (1). Surveillance for WNV infection includes monitoring of mosquitoes, sentinel
      chicken flocks, wild birds, and potentially susceptible mammals (e.g., horses and
      humans) (2). This report summarizes findings of this surveillance system through
      August 7, 2000.

PMID- 10958588
TI  - Publication of Surgeon General's report on smoking and health.
AB  - The Surgeon General's report Reducing Tobacco Use (1) was released on August 9,
      2000. This report is the first in the series to offer a composite review of the
      various methods used to reduce and prevent tobacco use.

PMID- 10958590
TI  - Studies on the cytotoxic, biochemical and anti-carcinogenic potentials of
      ninhydrin on Ehrlich ascites carcinoma cell-bearing Swiss albino mice.
AB  - Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and
      cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice.
      The rationale behind this study has been mainly the literature reports of its
      characteristic interference with DNA synthesis and calcium homeostasis. Antitumor
      activity was evaluated from the total count and viability of EAC cells in
      addition to their nucleic acid, protein, non-protein sulfhydryls (NP-SH) and
      malondialdehyde (MDA) contents. The EAC cell-bearing animals were also observed
      for the effect on their survival and body weight variations. In addition, the
      tumors grown at the site of injection were evaluated for histopathological
      changes. Ninhydrin treatments (5, 10 and 20 mg/kg/day) abate the increase in body
      weight and advanced the duration of survival in EAC cell-bearing mice. The
      results on histopathological investigations show retardation in tumor growth,
      decreased frequency of mitotic figures and hair follicles and an increased
      necrosis in the tumor by ninhydrin treatment. Our results on cytotoxicity, which
      demonstrated compression in the number of EAC cells and their viability
      substantiate these data. The results of biochemical studies on EAC cells exhibit
      a reduction in the levels of DNA, RNA, proteins and NP-SH with a subsequent
      increase in the concentrations of MDA after ninhydrin treatment. Inhibition in
      tumor growth was dose dependently significant with the same dose regimen. The
      observed cytotoxic and antitumor activity of ninhydrin was comparable to
      cyclophosphamide. The possible mode of action of ninhydrin-induced cytotoxic and
      antitumor activity appear to be due to its interference with mitochondrial
      function resulting in inhibition of DNA synthesis, an effect that is being
      investigated further.

PMID- 10958592
TI  - Phase II study of intravenous Doxil in malignant pleural mesothelioma.
AB  - Twenty-four patients with pleural mesothelioma received 50 mg/m2 of Doxil every
      four weeks. At follow-up, the disease had stabilized in 43% percent of patients
      and had progressed in 57%. No objective responses were observed. Estimated median
      survival of all patients was 37 weeks. Major toxicities were erythrodysesthesia
      of hands and feet and myelosuppression. No cardiac toxicity was observed. We
      concluded that Doxil at this dosage and schedule is inactive against pleural
      mesothelioma.

PMID- 10958589
TI  - Development of multidrug-resistance convertors: sense or nonsense?
AB  - This review describes the clinical relevance of the two drug transporters P
      glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) and the in
      vitro phenomenon which is referred to as multidrug resistance (MDR). The attempts
      to try to block these resistance mechanisms are summarized with specific
      attention for the intentionally designed "second generation" MDR-convertors.
      Potential explanations of the limited clinical success rate are given and
      recommendations for the design of future studies provided.

PMID- 10958593
TI  - Phase II trial of pyrazoloacridine as second-line therapy for patients with
      unresectable or metastatic transitional cell carcinoma.
AB  - PURPOSE: A phase II trial of pyrazoloacridine (PZA) was conducted to assess its
      activity and toxicity in patients with advanced transitional cell carcinoma (TCC)
      refractory to or progressing after one prior cisplatin-, carboplatin- or
      paclitaxel- based regimen. PATIENTS AND METHODS: PZA at a dose of 750 mg/m2 was
      administered to 14 patients as a three-hour intravenous infusion on day 1 every
      21 days. Premedication consisted of lorazepam 0.5-1.0 mg prior to each cycle to
      alleviate central nervous system toxicity. Reduction of subsequent doses was made
      for hematologic or central nervous system toxicity. RESULTS: Among fourteen
      patients evaluable for response, no responses were observed (0% response rate;
      95% confidence interval 0% to 23%). The median duration of survival for all
      patients was 9 months with a median follow-up of 8.5 months. Toxicity to PZA
      included grade 3 or 4 neutropenia in 8/14 (57%) and grade 3 or 4 thrombocytopenia
      in 2/14 (14%). Non-hematologic toxicity was mild. CONCLUSIONS: PZA at this dose
      and schedule does not have significant single-agent activity in patients with TCC
      who have failed one prior regimen.

PMID- 10958591
TI  - The oral route for the administration of cytotoxic drugs: strategies to increase
      the efficiency and consistency of drug delivery.
AB  - There is an increasing interest to administer cytotoxic drugs to patients by the
      oral route. Quality of life issues, treatment advantages and pharmaco-economics
      are major arguments in favor of oral therapy. However, low or moderate
      bioavailability in combination with considerable interpatient variability are
      frequently observed which may reduce the feasibility of the oral route for this
      class of drugs with a generally narrow therapeutic window. Until recently,
      investigators focused on absorption enhancers which slightly damage the
      intestinal surface such as salicylates, methylxanthines and surfactants to
      improve the oral bioavailability of drugs. To date, a shift can be seen towards
      more subtle mechanisms to enhance the absorption. This review article focuses on
      two important mechanisms that determine the oral bioavailability of cytotoxic
      drugs. These include the presence of drug transporters in the intestinal
      epithelium pumping drugs into the intestinal lumen, such as MDR1 type P
      glycoproteins, and first-pass elimination by cytochrome P450 isoenzymes (e.g. 3A4
      and 3A5) or other enzymes in the intestines and/or liver. Currently preclinical
      and clinical studies are being performed to explore the feasibility of blocking
      these transporters/enzymes in order to achieve higher and less variable systemic
      drug levels after oral dosing. This review gives an update of the results of
      these studies. It is concluded however, that further research to unravel the
      processes involved in oral drug uptake is warranted to make the oral route a more
      efficient and consistent way of drug administration.

PMID- 10958594
TI  - Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas.
AB  - PURPOSE: To assess the objective response rate, toxicity experienced, progression
      free survival, and overall survival of patients with previously untreated
      advanced soft tissue sarcomas treated with a liposomal doxorubicin formulation
      (Doxil). METHODS: Patients with metastatic or recurrent soft tissue sarcoma who
      had received no prior chemotherapy for advanced disease were treated with
      liposomal doxorubicin (Doxil) according to a two stage accrual design. Doxil was
      administered at 50 mg/m2 every 4 weeks. A total of 15 patients were treated and
      are evaluable for response and toxicity. RESULTS: The male/female ratio was 7/8,
      the median age was 60 years (34-75) and the ECOG performance status was 0-1 in
      >90% of patients. Leiomyosarcoma (7/15) and malignant fibrous histiocytoma (2/15)
      were the most common histologic diagnoses. No objective responses were observed
      in the 15 evaluable patients. No lethal toxicity occurred. Grade 3-4 leukopenia
      or neutropenia were reported in 3/15 (20%) patients. Grade 3 mucositis or hand
      foot syndrome occurred in 2/15 (13%) and 1/15 (7%) patients respectively and
      seemed more severe in older patients. The median time to progression was 1.9
      months (range 0.9-6.2). Twelve patients have now died. The Kaplan-Meier estimate
      of median overall survival is 12.3 months. As called for in the study design,
      accrual was terminated because no responses were obtained in the first 15
      patients. CONCLUSION: Though well-tolerated, Doxil given according to this dose
      and schedule to patients with advanced soft tissue sarcoma had no significant
      therapeutic activity. A correlation between older age and skin/mucosal toxicity
      of Doxil is suggested in this study but needs confirmation. Future investigations
      of Doxil in soft tissue sarcomas should use a different schedule and dose.

PMID- 10958595
TI  - Phase II trial of aminocamptothecin (9-AC/DMA) in patients with advanced squamous
      cell head and neck cancer.
AB  - Fourteen patients with squamous cell carcinoma of the head and neck received 9
      AC/DMA infusions of 850 mg/M2/day over 72 hours. Eligibility criteria included
      good performance status, advanced disease incurable by conventional means, no
      prior treatment of metastatic disease, and measurable lesions for objective
      response assessment. The infusions were repeated at 21 day intervals until
      progression or prohibitive toxicity occurred. A median of 3 cycles (range 1-7)
      was given. No objective responses were observed. Median survival of the group was
      6 months. Toxicity was hematologic which was modest and promptly reversible. 9
      AC/DMA is inactive against this tumor type at the dose and schedule employed in
      this study.

PMID- 10958596
TI  - Phase II trial of pyrazoloacridine in patients with cisplatin-refractory germ
      cell tumors.
AB  - Thirteen patients with cisplatin-refractory germ cell tumors were treated on a
      Phase II trial with pyrazoloacridine. Pyrazoloacridine was given intravenously at
      600 mg/m2 every three weeks. The median nadir leucocyte count was 2.5 cells/mm3,
      hemoglobin was 10.8 g/dl, and platelet count was 126,000 cells/m3. None of the
      thirteen evaluable patients achieved a major response. Pyrazoloacridine is not
      efficacious in the treatment of cisplatin-refractory germ cell tumors.

PMID- 10958597
TI  - A phase II trial of etoposide, leucovorin, 5-FU, and interferon alpha 2b (ELFI) +
      G-CSF for patients with pancreatic adenocarcinoma: a Southwest Oncology Group
      study (SWOG 9413).
AB  - BACKGROUND: Chemotherapeutic treatments using combinations of etoposide,
      leucovorin and 5-FU (ELF) have shown activity in the treatment of
      gastrointestinal malignancies. Interferon alpha 2b is known to have
      antiproliferative effects on several cell lines and has well documented in vitro
      evidence of synergism with 5-FU. It was postulated that the combination of ELF
      and interferon alpha 2b would improve response rates and survival in patients
      with pancreas cancer. METHODS: Fifty-five eligible patients with locally-advanced
      or metastatic pancreatic adenocarcinoma received a regimen consisting of: i.v.
      leucovorin at 300 mg/m2/day on Days 1-3 (of 28-day cycle), i.v. etoposide at 80
      mg/m2/day on Days 1-3, i.v. 5-FU at 500 mg/m2/day on Days 1-3, subcutaneous
      interferon alpha 2b at 3 million units TIW, and subcutaneous G-CSF at 5
      microg/kg/day on Days 4-14 (or until WBC exceeds 10,000/microl). Patients with no
      evidence of disease progression continued on treatment for a total of 6 cycles.
      RESULTS: Complete response was demonstrated in 1 patient, partial response in 5
      patients (11% confirmed response rate). The median survival was 5 months, and the
      six-month survival rate was 40%. Ten patients completed all 6 cycles of
      treatment. Toxicity-related dose delays and reductions were necessary for most
      patients. CONCLUSIONS: Although the combination of ELF and interferon alpha 2b
      (ELFI) has modest activity in pancreatic cancer, it is a toxic and complex
      regimen that is not superior to other currently available approaches for the
      chemotherapeutic management of pancreatic cancer. ELFI cannot be recommended as a
      standard therapy.

PMID- 10958598
TI  - A North Central Cancer Treatment Group phase II trial of topotecan in relapsed
      gliomas.
AB  - Current systemic treatment options for patients with relapsed gliomas are
      limited. The topoisomerase I inhibitor topotecan has demonstrated broad antitumor
      activity in both preclinical studies as well as a number of phase I and II trials
      in humans. Studies in primates have shown good cerebrospinal fluid levels of
      topotecan following systemic administration. We therefore performed this phase II
      trial in patients who developed evidence of progressive glioma after definitive
      radiation therapy. Patients were treated with 1.5 mg/m2 intravenously daily for 5
      consecutive days repeated every three weeks. For patients who had received prior
      nitrosourea-containing chemotherapy, the starting dose was 1.25 mg/m2. Thirty
      three patients were entered on this study. All patients were eligible and
      evaluable for both response and toxicity. Seven patients experienced grade 4
      leukopenia with 2 of these patients dying of infection-related complications. Six
      of these seven patients were not taking anticonvulsants during treatment. Nine
      patients developed grade 3-4 thrombocytopenia, seven of whom were not taking
      anticonvulsants. Nonhematologic side effects were infrequent and manageable. One
      patient experienced a partial response to this treatment for an overall response
      rate of 3% (95% binomial confidence interval 0.3%-20.4%). The median time to
      progression was 14.9 weeks and median survival 19.9 weeks. Topotecan at this dose
      and schedule showed no substantial activity in relapsed gliomas.

PMID- 10958600
TI  - Correlation of automated visual field parameters and peripapillary nerve fiber
      layer thickness as measured by scanning laser polarimetry.
AB  - PURPOSE: To correlate Humphrey visual field mean sensitivity and peripapillary
      nerve fiber layer thickness as measured by scanning laser polarimetry. METHODS:
      The authors studied 54 eyes of 34 patients who visited a university-based
      glaucoma clinic and had undergone scanning laser polarimetry and Humphrey
      perimetry within 6 months. The study population included normal patients and
      those with glaucoma, ocular hypertension, and glaucoma suspect. The authors
      correlated visual field sensitivity with peripapillary nerve fiber thickness, and
      visual field mean deviation with the average deviation from the normal nerve
      fiber layer thickness. They also correlated the visual field mean deviation with
      all available GDx Nerve Fiber Analyzer parameters. RESULTS: The visual field mean
      sensitivity and deviation showed a bilinear correlation to peripapillary nerve
      fiber layer thickness. The visual field mean sensitivity changed little when the
      nerve fiber layer thickness was greater than 70 microm. The nerve fiber layer
      thickness below this level was associated with a rapid decrease in the visual
      field sensitivity. Similarly, the visual field mean deviation was close to 0 dB
      when the nerve fiber layer was within -10 microm of the normal value; below this
      thickness, the mean deviation became substantially more negative. There was a
      large individual variability around the bilinear fit. Of the scanning laser
      polarimetry parameters, a calculated index, referred to as the number, had the
      highest correlation with the Humphrey mean deviation. CONCLUSION: The bilinear
      correlation and its variability between the scanning laser polarimetry and visual
      field parameters make it difficult to predict the result of one from the other.
      In general, the correlation between the two is better when there is a significant
      visual field defect than when the visual field is close to normal.

PMID- 10958601
TI  - Response time prolongation for a motion stimulus in patients with glaucoma and
      its relationship with elevation of the motion threshold.
AB  - PURPOSE: To investigate whether response times for a motion stimulus are
      prolonged in glaucoma and to investigate the relationship between response time
      prolongation and motion threshold elevation in glaucoma. METHOD: Motion
      displacement thresholds and response times were measured in 15 patients with
      glaucoma and 18 age-matched control subjects. RESULTS: Mean test response times
      were significantly prolonged in the glaucomatous eyes than in the control eyes,
      with a mean delay of 200 milliseconds. After correcting for threshold elevation,
      response times at the motion threshold showed no significant difference between
      the groups. CONCLUSIONS: Response times for motion detection are significantly
      prolonged in glaucoma and are accounted for by the threshold elevation in
      patients with glaucoma. The implications of these results are discussed in terms
      of the use of response time analysis to determine subject reliability.

PMID- 10958602
TI  - Reduced recovery of temporal contrast sensitivity after flicker stress in
      patients with glaucoma.
AB  - PURPOSE: To compare recovery of temporal contrast sensitivity after flicker
      stress between control subjects and patients with glaucoma. METHODS: Forty-three
      patients with primary open-angle glaucoma and secondary open-angle or normal
      tension glaucoma of the Erlangen Glaucoma Registry and 30 healthy control
      subjects had their temporal contrast sensitivity measured at 37 Hz and their
      recovery time determined after monocular exposure to 30 seconds of 58% contrast
      full-field flicker. Recovery time of temporal contrast sensitivity was measured
      as the time interval from cessation of flicker until twice the threshold value
      was reached. RESULTS: Patients with glaucoma had a significant reduction in
      temporal contrast sensitivity (P < 0.001). Recovery time was also significantly
      longer in patients with glaucoma (23.8 +/- 24.1 seconds) than in control subjects
      (7.6 +/- 2.6 seconds; P < 0.001). There was a significant positive correlation
      between recovery time and mean visual field defect (0.5; P < 0.001) and a
      significant negative correlation between recovery time and neuroretinal rim area
      of the optic disc (0.32; P = 0.04). CONCLUSIONS: Recovery of temporal contrast
      sensitivity after flicker stress is impaired in some patients with glaucoma. This
      might be the result of functional impairment of the inner retina, outer retina,
      or both in glaucoma.

PMID- 10958599
TI  - A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based
      combination chemotherapy with or without amifostine in patients with solid
      tumors.
AB  - This study evaluates the degree of kidney damage during cisplatin/ifosfamide
      based combination chemotherapy and its possible prevention by amifostine. Thirty
      one patients with solid tumors stratified according to pretreatment were
      randomized to receive VIP- or TIP-chemotherapy with or without amifostine (910
      mg/m2) given as a short infusion prior to cisplatin. Chemotherapy consisted of
      cisplatin (50 mg/m2), ifosfamide (4 g/m2) and either etoposide (500 mg/m2) (=
      VIP) or paclitaxel (175 mg/m2) (= TIP) repeated at 3 weekly intervals. For all
      patients the glomerular filtration rate (GFR) measured by creatinine-clearance,
      serum creatinine, electrolytes and differential urinary protein/enzyme excretion
      were determined prior to, during and after each cycle. A total of 62 cycles of
      chemotherapy were evaluable. In the amifostine-group GFR was fully maintained
      after application of two cycles of chemotherapy, whereas in the control group a >
      30%-reduction of median GFR (108 to 80 ml/min) was observed (p < 0.001). Patients
      receiving amifostine had a lower degree of high molecular weight proteins
      excretion indicating less glomerular damage. In both groups significant increases
      of tubular marker profiles peaking at day 3 after chemotherapy were observed with
      a nearly complete reversibility of these changes prior to the next chemotherapy
      cycle. The number of patients with low magnesium serum levels during treatment
      was 17% after amifostine application versus 69% in control patients. The results
      seem to indicate that treatment with amifostine can preserve GFR after
      application of two cisplatin/ifosfamide-based chemotherapy cycles. This may be
      advantageous if repetitive cycles of chemotherapy or subsequent administration of
      high dose chemotherapy is planned.

PMID- 10958604
TI  - Management of glaucoma implants occluded by vitreous incarceration.
AB  - PURPOSE: To review the authors' experience in the management of aphakic or
      pseudophakic patients without an intact posterior capsule who had undergone
      glaucoma implant surgery complicated by vitreous incarceration in the tube,
      resulting in increased intraocular pressure or combined rhegmatogenous and
      tractional retinal detachment. METHODS: Retrospective review of the clinical
      features, treatment, and outcomes of eight patients who had vitreous
      incarceration in a glaucoma implant drainage tube. In each patient, a model 425
      (7 patients) or model 350 (1 patient) Baerveldt glaucoma implant was used.
      RESULTS: Vitreous incarceration in the tube was first diagnosed 1 day to 49 weeks
      after surgery (mean, 7.5 weeks; median, 1 week). The interval between glaucoma
      implant surgery and pars plana vitrectomy ranged from 22 to 365 days (mean, 125
      days). Before management with pars plana vitrectomy or neodymium:yttrium-aluminum
      garnet laser vitreolysis, intraocular pressure ranged from 25 to 62 mm Hg (mean,
      40 mm Hg). Four patients were initially treated with neodymium:yttrium-aluminum
      garnet laser vitreolysis, which was successful in only one patient. Six patients
      were successfully treated with pars plana vitrectomy, and one patient declined
      surgery. Follow-up after treatment of the incarceration ranged from 5 weeks to 15
      months (mean, 8.3 months). After pars plana vitrectomy, intraocular pressure
      ranged from 9 to 24 mm Hg (average, 14 mm Hg). Postoperative visual acuity
      remained within one line of the preoperative visual acuity in each of the six
      patients undergoing pars plana vitrectomy. CONCLUSIONS: Pars plana vitrectomy is
      effective in managing vitreous incarceration in glaucoma implant tubes. Previous
      anterior vitrectomy does not prevent incarceration.

PMID- 10958603
TI  - Effects of atropine on anterior chamber depth and anterior chamber inflammation
      after primary trabeculectomy.
AB  - PURPOSE: To investigate the effects of postoperative atropine on central and
      peripheral anterior chamber depth and anterior chamber inflammation in patients
      undergoing primary trabeculectomy. METHODS: Two separate groups of patients who
      were phakic without previous intraocular surgery undergoing primary
      trabeculectomy were prospectively randomized to atropine or no atropine. In the
      first group of patients, 24 eyes of 21 patients undergoing primary trabeculectomy
      were prospectively randomized to atropine or no atropine, and their anterior
      chamber depth was measured. Central and peripheral chamber depths were measured
      using the EAS-1000 anterior segment analysis system (Nidek, Tokyo, Japan) before
      surgery and on postoperative days 1, 3, 7, 14, and 30. In the second group, 34
      patients undergoing primary trabeculectomy were prospectively randomized to
      atropine or no atropine, and their anterior chamber reaction was documented. The
      amount of cells and flare was measured using the Kowa laser flare meter (FM-500)
      and cell counter (LC-500) (Kowa Electronics and Optics, Tokyo, Japan)
      preoperatively and on postoperative day 1, 7, and 30. RESULTS: Compared with
      preoperative measurements, a small (approximately 0.1 mm) but statistically
      significant deepening of the central and peripheral anterior chamber depth on
      days 1, 7, 14, and 30 was found in patients who used atropine. In the nonatropine
      group, no statistically significant change was found in central or peripheral
      anterior chamber depths at any time as compared with preoperative values. There
      was no statistically significant difference in the cell or flare counts between
      the atropine and nonatropine groups at any time. CONCLUSIONS: This study showed a
      small but statistically significant deepening of the anterior chamber with
      atropine. No statistically significant differences were observed in the cell or
      flare counts between atropine and nonatropine groups. Routine atropine use after
      trabeculectomy may not be necessary to reduce postoperative complications, such
      as shallowing of the anterior chamber or anterior chamber inflammation. In
      patients with a shallow anterior chamber, however, atropine would be expected to
      deepen the chamber.

PMID- 10958606
TI  - Effect of wind instrument playing on intraocular pressure.
AB  - PURPOSE: To evaluate the effect of wind instrument playing on intraocular
      pressure. METHODS: In a prospective, nonrandomized clinical trial, 24 eyes of 24
      wind instrument players with no history of any ocular or systemic disease were
      evaluated. The musicians were members of Bilkent Academic Symphony Orchestra of
      Bilkent University in Ankara. A complete eye examination, including best
      corrected visual acuity, slit-lamp examination, and fundus examination, was
      performed. The intraocular pressure was measured before and after a 90-minute
      rehearsal of a piece by Wagner. All intraocular pressure measurements were
      carried out by the same researcher using Goldmann applanation tonometry. The
      difference in intraocular pressure measurements before and after the 90-minute
      wind instrument-playing performance was analyzed. RESULTS: The mean intraocular
      pressure was 13.79 +/- 1.93 mm Hg before and 15.12 +/- 2.44 mm Hg after the
      performance. Wind instrument playing significantly increased the mean intraocular
      pressure by 9.6% (P = 0.0149). CONCLUSION: These results indicate that wind
      instrument playing may significantly increase intraocular pressure in healthy
      patients. The significance of this finding for patients with suspected normal
      tension or high-tension glaucoma needs further evaluation.

PMID- 10958605
TI  - Visually significant cystoid macular edema in pseudophakic and aphakic patients
      with glaucoma receiving latanoprost.
AB  - PURPOSE: To investigate the incidence of visually significant cystoid macular
      edema associated with the use of latanoprost in patients with glaucoma after
      cataract surgery. PATIENTS AND METHODS: This is a multicenter, retrospective
      study of 185 patients, of whom 173 were pseudophakic (212 eyes) and 12 were
      aphakic (13 eyes), who were treated for glaucoma with latanoprost 0.005%. The
      posterior lens capsule was intact in 125 eyes, open or absent as a result of
      surgery in 25 eyes, and status-post-yttrium-aluminum-garnet capsulotomy in 75
      eyes. Visual acuity was documented before and after initiating latanoprost
      therapy, and patients with a reduction of two or more lines on the Snellen chart
      were examined by fluorescein angiography for cystoid macular edema. RESULTS:
      Visual reduction was documented in four (2.16%) patients. Three of the four
      patients had cystoid macular edema, and the fourth was thought to have lost a
      central island of vision from glaucoma. The three patients with cystoid macular
      edema all had ruptured posterior capsules, requiring anterior vitrectomy, and one
      had a previous episode of cystoid macular edema 3 years before starting
      latanoprost therapy. CONCLUSION: These findings suggest that visually significant
      cystoid macular edema associated with latanoprost therapy in pseudophakic or
      aphakic patients is uncommon. If there is a cause-and-effect relationship between
      latanoprost therapy and clinically significant cystoid macular edema, the
      incidence appears to be low.

PMID- 10958607
TI  - Endoscopic goniotomy with the free electron laser in congenital glaucoma rabbits.
AB  - PURPOSE: Goniotomy is a surgical treatment of choice to treat primary infantile
      glaucoma. Goniotomy has been studied in vitro in animal and human cadaver eyes
      with several lasers. The objective of this study was to investigate the
      functional and morphologic effectiveness of goniotomy with the free electron
      laser in comparison with conventional needle goniotomy in early congenital
      glaucoma rabbits. MATERIALS AND METHODS: Ten rabbits with early congenital
      glaucoma underwent goniotomy over 100 to 120 degrees with a needle or the free
      electron laser. The wavelength was 6.45 microm, and the energy level ranged from
      2.2 to 3.5 mJ at 30 Hz. Because most corneas were edematous in these rabbits, an
      Olympus 0.8-mm diameter endoscope was coupled to the laser waveguide or the
      needle and inserted into the anterior chamber filled with a viscoelastic material
      to perform the goniotomy. Intraocular pressures were followed up to 3 weeks
      before an acute goniotomy was performed in the contralateral eye. All eye
      specimens were processed for light microscopic evaluation. RESULTS: Incision of
      the pectinate ligaments and underlying trabecular meshwork was visualized through
      the endoscope on a video monitor during the surgeries. The mean intraocular
      pressure decreased after free electron laser goniotomy and after needle
      goniotomy, and the edematous corneas became clear in some cases. Histologic study
      showed successful lysing of the pectinate ligaments by the free electron laser
      with no obvious collateral thermal damage. However, some areas of peripheral
      anterior synechiae occurred. Similar results were observed in needle goniotomy
      cases. CONCLUSIONS: The free electron laser is capable of performing goniotomy in
      rabbit eyes with lower intraocular pressures in treated eyes 3 weeks after
      surgery. The histologic results of free electron laser goniotomy are comparable
      to those of conventional goniotomy. The endoscope provides beneficial
      visualization to perform the goniotomy in eyes with edematous corneas. The rabbit
      with early congenital glaucoma is also a useful infantile glaucoma surgical
      model.

PMID- 10958608
TI  - Effect of calcium channel blockers alone and in combination with antiglaucoma
      medications on intraocular pressure in the primate eye.
AB  - PURPOSE: To determine the effect of representative members from six classes of
      calcium channel blockers on intraocular pressure in the primate eye. Other
      antiglaucoma medications were administered with verapamil to determine their
      combined effect on intraocular pressure. METHODS: Six healthy cynomolgus monkeys
      were anesthetized, and baseline intraocular pressure was measured. Drug
      containing solution (50 microL) was instilled in one eye and intraocular pressure
      was measured in both eyes 90 minutes later. RESULTS: All classes of calcium
      channel blockers significantly lowered intraocular pressure in the treated eye.
      The percent reduction in intraocular pressure compared with the baseline pressure
      was 10% for verapamil (P < 0.002), 18% for nifedipine (P < 0.001), 15% for
      diltiazem (P < 0.001), 17% for flunarizine (P < 0.001), 19% for prenylamine (P <
      0.001), and 6% for perhexiline (P < 0.01). In the fellow eye, a significant
      reduction in intraocular pressure was also seen with all calcium channel blockers
      except perhexiline, which suggested a crossover effect. In contrast, neither
      vehicle treated nor contralateral eyes showed a lowering of intraocular pressure
      when tested under the same conditions. In the treated eye, 0.5% timolol (P <
      0.01) and 0.05% clonidine (P < 0.02) combined with 0.25% verapamil each appeared
      to produce an additive effect, with a significantly greater pressure-lowering
      effect than either agent alone. In addition, 0.005% pilocarpine (P < 0.001) and
      0.00125% demecarium (P < 0.01) combined with 0.25% verapamil each appeared to
      produce a synergistic effect, with a significantly greater reduction in
      intraocular pressure than both agents combined. CONCLUSIONS: Topical calcium
      channel blockers and combinations of verapamil with antiglaucoma medications may
      provide a useful alternative for reducing intraocular pressure in patients with
      ocular hypertension or primary open-angle glaucoma.

PMID- 10958609
TI  - Ultrasound biomicroscope findings in carotid-cavernous fistula.

PMID- 10958610
TI  - Application of vibrational spectroscopy to the study of mineralized tissues
      (review).
AB  - The infrared and Raman spectroscopy of bone and teeth tissues are reviewed.
      Characteristic spectra are obtained for both the mineral and protein components
      of these tissues. Vibrational spectroscopy is used to study the mineralization
      process, to define the chemical structure changes accompanying bone diseases, and
      to characterize interactions between prosthetic implants and tissues.
      Microspectroscopy allows acquisition of spatially resolved spectra, with micron
      scale resolution. Recently developed imaging modalities allow tissue imaging with
      chemical composition contrast.

PMID- 10958611
TI  - Blood flow and oxygen consumption with near-infrared spectroscopy and venous
      occlusion: spatial maps and the effect of time and pressure of inflation.
AB  - We have measured the local blood flow (BF) and oxygen consumption (OC) in the
      human calf muscle using near-infrared spectroscopy during venous occlusion.
      Venous occlusion was achieved by inflating a pneumatic cuff around the thigh of
      the subject. We have investigated the influence of the inflation time and cuff
      pressure on the recovered values of BF and OC. We have found that if the cuff
      pressure is increased from a threshold pressure (approximately 30 mm Hg) to a
      critical pressure (approximately 45 mm Hg) in less than about 6 s, one measures
      the same values of BF and OC independent of the total inflation time and final
      cuff pressure. We also report nine-pixel spatial maps of BF and OC to show that
      this technique can lead to spatially resolved measurements of blood flow and
      oxygen consumption in tissues.

PMID- 10958612
TI  - Modeling photon transport in transabdominal fetal oximetry.
AB  - The possibility of optical oximetry of the blood in the fetal brain measured
      across the maternal abdomen just prior to birth is under investigation. Such
      measurements could detect fetal distress prior to birth and aid in the clinical
      decision regarding Cesarean section. This paper uses a perturbation method to
      model photon transport through an 8-cm-diam fetal brain located at a constant 2.5
      cm below a curved maternal abdominal surface with an air/tissue boundary. In the
      simulation, a near-infrared light source delivers light to the abdomen and a
      detector is positioned up to 10 cm from the source along the arc of the abdominal
      surface. The light transport [W/cm2 fluence rate per W incident power] collected
      at the 10 cm position is Tm = 2.2 x 10(-6) cm(-2) if the fetal brain has the same
      optical properties as the mother and Tf = 1.0 x 10(-6) cm(-2) for an optically
      perturbing fetal brain with typical brain optical properties. The perturbation
      P=(Tf - Tm)/Tm is -53% due to the fetal brain. The model illustrates the
      challenge and feasibility of transabdominal oximetry of the fetal brain.

PMID- 10958613
TI  - Changes in cerebral hemoglobin concentration and oxygen saturation immediately
      after birth in the human neonate using full-spectrum near infrared spectroscopy.
AB  - Using full-spectrum near infrared spectroscopy (fsNIRS), we measured changes in
      oxy- and deoxyhemoglobin (HbO2 and Hb), total hemoglobin (T-Hb) concentration,
      and hemoglobin oxygen saturation (SbO2) in the brain tissue of seven neonates
      immediately following birth. It was found that HbO2 rose rapidly within 2-3 min
      after birth. During the same time, there was a transient increase in T-Hb
      concentration, after which it decreased together with Hb. SbO2 increased rapidly
      after birth, from 18% at 1.5 min to about 55% at 5-6 min, followed by a gradual
      increase of about 10%. Oxygenation in the brain occurred much sooner in three
      subjects given oxygen for a short time immediately after birth than in those who
      did not receive oxygen. This preliminary study indicated that dynamic changes
      occur in cerebral circulation and oxygenation as part of the physiological
      changes taking place soon after birth.

PMID- 10958614
TI  - Noninvasive cerebral blood volume measurement during seizures using multichannel
      near infrared spectroscopic topography.
AB  - Near infrared spectroscopic topography (NIRS) is widely recognized as a
      noninvasive method to measure the regional cerebral blood volume (rCBV) dynamics
      coupled with neuronal activities. We analyzed the rCBV change in the early phase
      of epileptic seizures in 12 consecutive patients with medically intractable
      epilepsy. Seizure was induced by bemegride injection. We used eight-channel NIRS
      in nine cases and 24 channel in three cases. In all of the cases, rCBV increased
      rapidly after the seizure onset on the focus side. The increased rCBV was
      observed for about 30-60 s. The NIRS method can be applied to monitor the rCBV
      change continuously during seizures. Therefore, this method may be combined with
      ictal SPECT as one of the most reliable noninvasive methods of focus diagnosis.

PMID- 10958615
TI  - Theoretical foundations for noninvasive measurement of variations in the width of
      the subarachnoid space.
AB  - Numerical modeling was used for the theoretical analysis of the propagation of
      optical radiation in the tissues of the human head, generated by a single source
      placed on the surface of the scalp. Of special interest and importance is the
      propagation of radiation within the layer of cerebrospinal fluid contained in the
      subarachnoid space (SAS), which is the only low absorption/high transmittance
      medium whose width can vary rapidly. Qualitative and quantitative assessment of
      changes in propagation of radiation within the SAS could become a source of
      information on changes in the geometry of this anatomical compartment playing a
      crucial role in cranio-spinal physiology and pathology. Essential for the idea of
      the possible noninvasive assessment of changes in width of the SAS by an optical
      method is the dependence of intensity of radiation reaching a photodetector
      located at a certain distance from the source on changes in the width of this
      fluid layer, which acts like a biological optical waveguide. Monte Carlo modeling
      and numerical analysis confirmed the feasibility of assessing changes in the
      width of the subarachnoid space optically. Presented here are details of the
      Monte Carlo simulation of light propagation in the tissues of human head and the
      results of such simulation as a function of the width of the subarachnoid space,
      calculated for different distances between the source and detector and for a few
      selected values of bone thickness. Results of numerical modeling were then
      compared with those of experiments on a mechanical-optical model.

PMID- 10958616
TI  - Consequences of scattering for spectral imaging of turbid biologic tissue.
AB  - Spectral imaging permits two-dimensional mapping of the backscattering properties
      of biological systems. Such mapping requires broadband illumination of the entire
      area of interest. However, imaging of turbid biological media under these
      conditions often involves mean photon path lengths that exceed the pixel size.
      Using a numerical Monte Carlo model, we have studied the effects of photon
      scattering in a hemoglobin-bearing model system. We find that photon migration
      and the resulting wavelength-dependent optical coupling between pixels can
      complicate the analysis of imaging spectroscopy data. In fact, the wavelength
      dependence of photon trajectories also alters the distribution of photon exit
      angles at the tissue surface. We therefore find that the finite optical field of
      view of an imaging spectrometer can affect the measured spectra in the absence of
      chromatic aberrations.

PMID- 10958617
TI  - On the use of schematic eye models to estimate retinal image quality.
AB  - The optical performance of the eyes of nine vertebrate species was evaluated
      using optical system design techniques and schematic eye models. Essential
      features of eyes, including the modulation transfer function (MTF) and the MTF
      cutoff frequency are related to the numerical aperture of the eyes. Superior
      resolution for in vivo imaging of photoreceptors may be achieved by dilating the
      iris pupil of an eye, minimizing coherence, and using short wavelength
      illumination. The difference of lateral and axial resolution between a small and
      a large eye for imaging photoreceptors in vivo.

PMID- 10958618
TI  - Comparison of macular versus paramacular retinal sensitivity to femtosecond laser
      pulses.
AB  - Single 130 fs laser pulses in the near-IR (800 nm) were used to create
      ophthalmoscopically viewed minimum visible lesions (MVLs) within the macular and
      paramacular regions in rhesus monkey eyes. MVL thresholds at 1 and 24 h are
      reported as the 50% probability for damage (ED50) together with their fiducial
      limits at the 95% confidence level. These measured thresholds are compared with
      previously reported thresholds for near-IR and visible wavelengths for both
      macular and paramacular areas. Threshold doses were lower at the 24 h reading
      than at the 1 h reading for both retinal regions and the ED50s for the macula
      were slightly lower than for the paramacula. We measured the 24 h MVL ED50
      thresholds to be 0.35 and 0.55 microJ for the macular and paramacular areas,
      respectively. The combined data for both areas yielded a threshold of 0.45
      microJ.

PMID- 10958619
TI  - Analysis of the optical properties of bile.
AB  - Invasive bile determination is very useful in the diagnosis of many gastric
      pathologies. At the moment, this measurement is performed with Bilitec 2000, an
      optical fiber sensor, that is based on absorption by bilirubin. Nevertheless,
      erroneous evaluations are possible, due to the different configurations which the
      bilirubin molecule can adopt. The optical behavior of human samples of pure bile
      and bile+gastric juice has been examined using an optical fiber spectrophotometer
      and two suitably modified Bilitec 2000 units. A protocol has been established for
      the treatment of biological fluids, in order to make it possible to study the
      behavior of their optical properties as a function of pH and concentration
      without causing any alteration in the samples. The analysis of pH dependence
      evidenced the presence of different calibration curves at different pH values:
      the self-aggregation of the bilirubin molecules observed in pure bile samples was
      almost totally absent in the gastric samples. Measurements carried out on Bilitec
      2000 showed that the most appropriate wavelength for bilirubin detection in the
      stomach should be 470 nm.

PMID- 10958620
TI  - Methodology for examining polarized light interactions with tissues and
      tissuelike media in the exact backscattering direction.
AB  - The properties of polarized light emerging from turbid media in the exact
      backscattering direction are studied by modulating the incident light
      polarization state and isolating the synchronous signal with lock-in amplifier
      detection. The results are reported for polystyrene microsphere suspensions in
      distilled water, with and without glucose, and for both ex vivo and in vivo
      biological tissues. A new theoretical formulation based on Mueller calculus is
      developed to describe the observed behavior of the backscattered light in terms
      of two sample parameters: optical rotation and depolarization. This technique
      proved successful in modeling both phantom and tissue samples. Results showed the
      presence of a significant surviving polarization fraction in the backscattering
      direction even in extremely dense optical phantom media, an important finding
      that has not been observed at other detection angles. Substantial polarized light
      preservation in biological tissue samples is also demonstrated for this detection
      geometry. This illustrates the potential of using polarized light to investigate
      turbid biological materials in vivo in retroreflection geometry.

PMID- 10958621
TI  - Study of photodynamic reactions in human blood.
AB  - Comparative studies of oxygen consumption, changes of photosensitizer
      fluorescence, and photodestruction of erythrocytes, and photodestruction of
      oxygen transport protein hemoglobin were performed during photodynamic reaction
      in whole and hemolyzed blood with phthalocyanines, chlorines, porphyrins, and
      methylene blue photosensitizers in vitro and in selected cases in vivo. The
      present work deals with the investigation of blood oxygen saturation SO2 and
      photosensitizer fluorescence during and immediately after light irradiation in
      the photodynamic therapy process. It has been observed that SO2 behavior strongly
      correlates with the type of photosensitizer. The decrease of photosensitizer
      fluorescence (photobleaching) during light irradiation can be followed by the
      recovery of the photosensitizer fluorescence immediately after interruption of
      the irradiation within 6-8 min. The levels of photodestruction of erythrocytes in
      whole blood and photodestruction of hemoglobin in hemolyzed blood in combination
      with the above photosensitizers reveal the influence of photodynamic reactions
      upon the ability of blood to transport oxygen. Maximal photohemolysis activity
      has been found with chlorine p6 photosensitizers.

PMID- 10958622
TI  - Antibody-based biosensor for breast cancer with ultrasonic regeneration.
AB  - We describe a novel method and instrumental setup for regenerating antibodies
      immobilized on a fiberoptic probe of an immunosensor using ultrasonic irradiation
      with broadband imaging transducers. The instrumental setup and irradiation
      conditions for antibody regeneration using ultrasound are described. The results
      of the measurements with antibody against breast cancer antigen illustrate the
      effectiveness and potential of the regenerable immunosensor. A 65% removal of the
      antigens bound to the Mab immobilized on the fiber surface is attained after
      ultrasound regeneration.

PMID- 10958623
TI  - A chimpanzee genome project is a biomedical imperative.

PMID- 10958624
TI  - WABA success: a tool for sequence comparison between large genomes.

PMID- 10958625
TI  - Guilt by association: contextual information in genome analysis.

PMID- 10958626
TI  - Automation for genomics, part one: preparation for sequencing.
AB  - In the past four years, automation for genomics has enabled a 43-fold increase in
      the total finished human genomic sequence in the world. This two-part
      noncomprehensive review will provide an overview of different types of automation
      equipment used in genome sequencing. Part One focuses on equipment involved in
      DNA preparation, DNA sequencing reactions, and other automated procedures for
      preparing DNA for running on sequencers or subsequent analysis; it also includes
      information on the development of these machines at various genome centers. Part
      Two, to be published in the next issue, will cover sequencing machinery and array
      technology, and conclude with a look at the future technologies that will
      revolutionize molecular biology. "Alternate" sequencing technologies (including
      mass spectrometry, biochips, and single-molecule analysis) will also be examined.

PMID- 10958627
TI  - Genomic sequence analysis of the mouse Naip gene array.
AB  - A mouse locus called Lgn1 determines differences in macrophage permissiveness for
      the intracellular replication of Legionella pneumophila. The only regional
      candidate genes for this phenotype difference lie within a cluster of closely
      linked paralogs of the Neuronal Apoptosis Inhibitory Protein (Naip) gene.
      Previous genetic and physical mapping of the Lgn1 phenotype narrowed it to an
      interval containing only Naip2 and Naip5, suggesting that there is not complete
      functional overlap among the mouse Naip loci. In order to gather more information
      about polymorphisms among the Naip genes of the 129 mouse haplotype, we have
      determined the genomic sequence of a substantial portion of the 129 Naip gene
      array. We have constructed an evolutionary model for the expansion of the Naip
      gene array from a single progenitor Naip gene. This model predicts the presence
      of two distinct families of Naip paralogs: Naip1/2/3 and Naip4/5/6/7. Unlike the
      divergences among all the other Naip paralogs, the splits among Naip4, Naip5,
      Naip6, and Naip7 occurred relatively recently. The high degree of sequence
      conservation within the Naip4/5/6/7 family increases the likelihood of functional
      overlap among these genes.

PMID- 10958630
TI  - Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C.
      elegans genomic alignment.
AB  - A new algorithm, WABA, was developed for doing large-scale alignments between
      genomic DNA of different species. WABA was used to align 8 million bases of
      Caenorhabditis briggsae genomic DNA against the entire 97-million-base
      Caenorhabditis elegans genome. The alignment, including C. briggsae homologs of
      154 genetically characterized C. elegans genes and many times this number of
      largely uncharacterized ORFs, can be browsed and searched on the Web
      (http://www.cse.ucsc.edu/ approximately kent/intronerator). The alignment
      confirms that patterns of conservation can be useful in identifying regulatory
      regions and rarely expressed coding regions. Conserved regulatory elements can be
      identified inside coding exons by examining the level of divergence at the wobble
      position of codons. The alignment reveals a bimodal size distribution of syntenic
      regions. Over 250 introns are present in one species but not the other. The 3'
      and 5' intron splice sites have more similarity to each other in introns unique
      to one species than in C. elegans introns as a whole, suggesting a possible
      mechanism for intron removal.

PMID- 10958629
TI  - GT repeats are associated with recombination on human chromosome 22.
AB  - The rate of meiotic recombination is not a constant function of physical distance
      across chromosomes. This variation is manifested by recombination hot spots and
      cold spots, observed in all organisms ranging from bacteria to humans. It is
      generally believed that factors such as primary and secondary DNA sequence, as
      well as chromatin structure and associated proteins, influence the frequency of
      recombination within a specific region. Several such factors, for example
      repetitive sequences, gene promoters, or regions with the ability to adopt Z-DNA
      conformation, have been hypothesized to enhance recombination. However, apart
      from specific examples, no general trends of association between recombination
      rates and particular DNA sequence motifs have been reported. In this paper, we
      analyze the complete sequence data from human chromosome 22 and compare
      microsatellite repeat distributions with mitotic recombination patterns available
      from earlier genetic studies. We show significant correlation between long tandem
      GT repeats, which are known to form Z-DNA and interact with several components of
      the recombination machinery, and recombination hot spots on human chromosome 22.

PMID- 10958628
TI  - Gene survey of the pathogenic protozoan Trypanosoma cruzi.
AB  - We have performed a survey of the active genes in the important human pathogen
      Trypanosoma cruzi by analyzing 5013 expressed sequence tags (ESTs) generated from
      a normalized epimastigote cDNA library. Clustering of all sequences resulted in
      771 clusters, comprising 54% of the ESTs. In total, the ESTs corresponded to 3054
      transcripts that might represent one-fourth of the total gene repertoire in T.
      cruzi. About 33% of the T. cruzi transcripts showed similarity to sequences in
      the public databases, and a large number of hitherto undiscovered genes predicted
      to be involved in transcription, cell cycle control, cell division, signal
      transduction, secretion, and metabolism were identified. More than 140 full
      length gene sequences were derived from the ESTs. Comparisons with all open
      reading frames in yeast and in Caenorhabditis elegans showed that only 12% of the
      T. cruzi transcripts were shared among diverse eukaryotic organisms. Comparison
      with other kinetoplastid sequences identified 237 orthologous genes that are
      shared between these evolutionarily divergent organisms. The generated data are a
      useful resource for further studies of the biology of the parasite and for
      development of new means to combat Chagas' disease.

PMID- 10958631
TI  - Genome-wide detection of allelic imbalance using human SNPs and high-density DNA
      arrays.
AB  - Most human cancers are characterized by genomic instability, the accumulation of
      multiple genetic alterations and allelic imbalance throughout the genome. Loss of
      heterozygosity (LOH) is a common form of allelic imbalance and the detection of
      LOH has been used to identify genomic regions that harbor tumor suppressor genes
      and to characterize tumor stages and progression. Here we describe the use of
      high-density oligonucleotide arrays for genome-wide scans for LOH and allelic
      imbalance in human tumors. The arrays contain redundant sets of probes for 600
      genetic loci that are distributed across all human chromosomes. The arrays were
      used to detect allelic imbalance in two types of human tumors, and a subset of
      the results was confirmed using conventional gel-based methods. We also tested
      the ability to study heterogeneous cell populations and found that allelic
      imbalance can be detected in the presence of a substantial background of normal
      cells. The detection of LOH and other chromosomal changes using large numbers of
      single nucleotide polymorphism (SNP) markers should enable identification of
      patterns of allelic imbalance with potential prognostic and diagnostic utility.

PMID- 10958633
TI  - Alfresco--a workbench for comparative genomic sequence analysis.
AB  - Comparative analysis of genomic sequences provides a powerful tool for
      identifying regions of potential biologic function; by comparing corresponding
      regions of genomes from suitable species, protein coding or regulatory regions
      can be identified by their homology. This requires the use of several specific
      types of computational analysis tools. Many programs exist for these types of
      analysis; not many exist for overall view/control of the results, which is
      necessary for large-scale genomic sequence analysis. Using Java, we have
      developed a new visualization tool that allows effective comparative genome
      sequence analysis. The program handles a pair of sequences from putatively
      homologous regions in different species. Results from various different existing
      external analysis programs, such as database searching, gene prediction, repeat
      masking, and alignment programs, are visualized and used to find corresponding
      functional sequence domains in the two sequences. The user interacts with the
      program through a graphic display of the genome regions, in which an
      independently scrollable and zoomable symbolic representation of the sequences is
      shown. As an example, the analysis of two unannotated orthologous genomic
      sequences from human and mouse containing parts of the UTY locus is presented.

PMID- 10958632
TI  - Discovery of a novel, paternally expressed ubiquitin-specific processing protease
      gene through comparative analysis of an imprinted region of mouse chromosome 7
      and human chromosome 19q13.4.
AB  - Using mouse BAC clones spanning an imprinted interval of proximal mouse
      chromosome 7 and the genomic sequence of the related interval of human chromosome
      19q13.4, we have identified a novel mouse gene, Usp29 (ubiquitin-specific
      processing protease 29), near two known imprinted genes, Peg3 and Zim1. Gene
      Usp29 is located directly adjacent to Peg3 in a "head-to-head" orientation, and
      comprises exons distributed over a genomic distance of at least 400 kb. A similar
      human gene is also found in the homologous location in human chromosome 19q13.4.
      The mouse Usp29 gene is also imprinted and is transcribed mainly from the
      paternal allele with highest expression levels in adult brain, especially in the
      cerebral cortex and hippocampus, and in the forebrain, face, and limb buds of
      midgestation mouse embryos. Analysis of a full-length 7.6-kb cDNA clone revealed
      that Usp29 encodes an 869-amino-acid protein that displays significant homology
      with yeast and nematode ubiquitin carboxyl-terminal hydrolases. These data
      suggest that, like the candidate Angelman syndrome gene Ube3a (ubiquitin ligase),
      Usp29 may represent another imprinted gene involved in the ubiquitination
      pathway. This identification of a third imprinted gene, Usp29, from the Peg3/Zim1
      region confirms the presence of a conserved imprinted domain spanning at least
      500 kb in the proximal portion of mouse chromosome 7 (Mmu7).

PMID- 10958634
TI  - High-resolution genetic and physical map of the Lgn1 interval in C57BL/6J
      implicates Naip2 or Naip5 in Legionella pneumophila pathogenesis.
AB  - Prior genetic and physical mapping has shown that the Naip gene cluster on mouse
      chromosome 13D1-D3 contains a gene, Lgn1, that is responsible for determining the
      permissivity of ex vivo macrophages to Legionella pneumophila replication. We
      have identified differences in the structure of the Naip array among commonly
      used inbred mouse strains, although these gross structural differences do not
      correlate with differences in L. pneumophila permissiveness. A physical map of
      the region employing clones of the C57BL/6J haplotype confirms that there are
      fewer copies of Naip in this strain than are in the physical map of the 129
      haplotype. We have also refined the genetic location of Lgn1, leaving only Naip2
      and Naip5 as candidates for Lgn1. Our genetic map suggests the presence of two
      hotspots of recombination within the Naip array, indicating that the 3' portion
      of Naip may be involved in the genomic instability at this locus.

PMID- 10958635
TI  - Eukaryote-specific domains in translation initiation factors: implications for
      translation regulation and evolution of the translation system.
AB  - Computational analysis of sequences of proteins involved in translation
      initiation in eukaryotes reveals a number of specific domains that are not
      represented in bacteria or archaea. Most of these eukaryote-specific domains are
      known or predicted to possess an alpha-helical structure, which suggests that
      such domains are easier to invent in the course of evolution than are domains of
      other structural classes. A previously undetected, conserved region predicted to
      form an alpha-helical domain is delineated in the initiation factor eIF4G, in
      Nonsense-mediated mRNA decay 2 protein (NMD2/UPF2), in the nuclear cap-binding
      CBP80, and in other, poorly characterized proteins, which is named the NIC (NMD2,
      eIF4G, CBP80) domain. Biochemical and mutagenesis data on NIC-containing proteins
      indicate that this predicted domain is one of the central adapters in the
      regulation of mRNA processing, translation, and degradation. It is demonstrated
      that, in the course of eukaryotic evolution, initiation factor eIF4G, of which
      NIC is the core, conserved portion, has accreted several additional, distinct
      predicted domains such as MI (MA-3 and eIF4G ) and W2, which probably was
      accompanied by acquisition of new regulatory interactions.

PMID- 10958636
TI  - Ecologic genomics of DNA: upstream bending in prokaryotic promoters.
AB  - After our analysis of the distribution of predicted intrinsic curvature along all
      available complete prokaryotic genomes, the genomes were divided into two groups.
      Curvature distribution in all prokaryotes of the first group indicated a
      substantial fraction of promoters characterized by intrinsic DNA curvature
      located within or upstream of the promoter region. We did not find this peculiar
      DNA curvature distribution in prokaryotes in the second group. Remarkably, all
      bacteria of the first group were mesophilic, whereas many prokaryotes of the
      second group were hyperthermophilic. We hypothesize that DNA curvature plays a
      biologic role in gene regulation in mesophilic as opposed to hyperthermophilic
      prokaryotes, i.e., DNA curvature presumably has a functional adaptive
      significance determined by temperature selection.

PMID- 10958637
TI  - Genomic sequence analysis of Fugu rubripes CFTR and flanking genes in a 60 kb
      region conserving synteny with 800 kb of human chromosome 7.
AB  - To define control elements that regulate tissue-specific expression of the cystic
      fibrosis transmembrane regulator (CFTR), we have sequenced 60 kb of genomic DNA
      from the puffer fish Fugu rubripes (Fugu) that includes the CFTR gene. This
      region of the Fugu genome shows conservation of synteny with 800-kb sequence of
      the human genome encompassing the WNT2, CFTR, Z43555, and CBP90 genes.
      Additionally, the genomic structure of each gene is conserved. In a multiple
      sequence alignment of human, mouse, and Fugu, the putative WNT2 promoter sequence
      is shown to contain highly conserved elements that may be transcription factor or
      other regulatory binding sites. We have found two putative ankyrin repeat
      containing genes that flank the CFTR gene. Overall sequence analysis suggests
      conservation of intron/exon boundaries between Fugu and human CFTR and revealed
      extensive homology between functional protein domains. However, the immediate 5'
      regions of human and Fugu CFTR are highly divergent with few conserved sequences
      apart from those resembling diminished cAMP response elements (CRE) and CAAT box
      elements. Interestingly, the polymorphic polyT tract located upstream of exon 9
      is present in human and Fugu but absent in mouse. Similarly, an intron 1 and
      intron 9 element common to human and Fugu is absent in mouse. The euryhaline
      killifish CFTR coding sequence is highly homologous to the Fugu sequence,
      suggesting that upregulation of CFTR in that species in response to salinity may
      be regulated transcriptionally.

PMID- 10958639
TI  - Loss of heterozygosity assay for molecular detection of cancer using energy
      transfer primers and capillary array electrophoresis.
AB  - Microsatellite DNA loci are useful markers for the detection of loss of
      heterozygosity (LOH) and microsatellite instability (MI) associated with primary
      cancers. To carry out large-scale studies of LOH and MI in cancer progression,
      high-throughput instrumentation and assays with high accuracy and sensitivity
      need to be validated. DNA was extracted from 26 renal tumor and paired lymphocyte
      samples and amplified with two-color energy-transfer (ET) fluorescent primers
      specific for loci associated with cancer-induced chromosomal changes. PCR
      amplicons were separated on the MegaBACE-1000 96 capillary array electrophoresis
      (CAE) instrument and analyzed with MegaBACE Genetic Profiler v.1.0 software.
      Ninety-six separations were achieved in parallel in 75 minutes. Loss of
      heterozygosity was easily detected in tumor samples as was the gain/loss of
      microsatellite core repeats. Allelic ratios were determined with a precision of
      +/- 10% or better. Prior analysis of these samples with slab gel electrophoresis
      and radioisotope labeling had not detected these changes with as much sensitivity
      or precision. This study establishes the validity of this assay and the MegaBACE
      instrument for large-scale, high-throughput studies of the molecular genetic
      changes associated with cancer.

PMID- 10958638
TI  - Predicting protein function by genomic context: quantitative evaluation and
      qualitative inferences.
AB  - Various new methods have been proposed to predict functional interactions between
      proteins based on the genomic context of their genes. The types of genomic
      context that they use are Type I: the fusion of genes; Type II: the conservation
      of gene-order or co-occurrence of genes in potential operons; and Type III: the
      co-occurrence of genes across genomes (phylogenetic profiles). Here we compare
      these types for their coverage, their correlations with various types of
      functional interaction, and their overlap with homology-based function
      assignment. We apply the methods to Mycoplasma genitalium, the standard
      benchmarking genome in computational and experimental genomics. Quantitatively,
      conservation of gene order is the technique with the highest coverage, applying
      to 37% of the genes. By combining gene order conservation with gene fusion (6%),
      the co-occurrence of genes in operons in absence of gene order conservation (8%),
      and the co-occurrence of genes across genomes (11%), significant context
      information can be obtained for 50% of the genes (the categories overlap).
      Qualitatively, we observe that the functional interactions between genes are
      stronger as the requirements for physical neighborhood on the genome are more
      stringent, while the fraction of potential false positives decreases. Moreover,
      only in cases in which gene order is conserved in a substantial fraction of the
      genomes, in this case six out of twenty-five, does a single type of functional
      interaction (physical interaction) clearly dominate (>80%). In other cases,
      complementary function information from homology searches, which is available for
      most of the genes with significant genomic context, is essential to predict the
      type of interaction. Using a combination of genomic context and homology
      searches, new functional features can be predicted for 10% of M. genitalium
      genes.

PMID- 10958640
TI  - High-resolution quantification of specific mRNA levels in human brain autopsies
      and biopsies.
AB  - Quantification of mRNA levels in human cortical brain biopsies and autopsies was
      performed using a fluorogenic 5' nuclease assay. The reproducibility of the assay
      using replica plates was 97%-99%. Relative quantities of mRNA from 16 different
      genes were evaluated using a statistical approach based on ANCOVA analysis.
      Comparison of the relative mRNA levels between two groups of samples with
      different time postmortem revealed unchanged relative expression levels for most
      genes. Only CYP26A1 mRNA levels showed a significant decrease with prolonged time
      postmortem (p = 0.00004). Also, there was a general decrease in measured mRNA
      levels for all genes in autopsies compared to biopsies; however, on comparing
      mRNA levels after adjusting with reference genes, no significant differences were
      found between mRNA levels in autopsies and biopsies. This observation indicates
      that studies of postmortem material can be performed to reveal the relative in
      vivo mRNA levels of genes. Power calculations were done to determine the number
      of individuals necessary to detect differences in mRNA levels of 1.5-fold to
      tenfold using the strategy described here. This analysis showed that samples from
      at least 50 individuals per group, patients and controls, are required for high
      resolution ( approximately twofold changes) differential expression screenings in
      the human brain. Experiments done on ten individuals per group will result in a
      resolution of approximately fivefold changes in expression levels. In general,
      the sensitivity and resolution of any differential expression study will depend
      on the sample size used and the between-individual variability of the genes
      analyzed.

PMID- 10958641
TI  - Tissue gene expression analysis using arrayed normalized cDNA libraries.
AB  - We have used oligonucleotide-fingerprinting data on 60,000 cDNA clones from two
      different mouse embryonic stages to establish a normalized cDNA clone set. The
      normalized set of 5,376 clones represents different clusters and therefore, in
      almost all cases, different genes. The inserts of the cDNA clones were amplified
      by PCR and spotted on glass slides. The resulting arrays were hybridized with
      mRNA probes prepared from six different adult mouse tissues. Expression profiles
      were analyzed by hierarchical clustering techniques. We have chosen radioactive
      detection because it combines robustness with sensitivity and allows the
      comparison of multiple normalized experiments. Sensitive detection combined with
      highly effective clustering algorithms allowed the identification of tissue
      specific expression profiles and the detection of genes specifically expressed in
      the tissues investigated. The obtained results are publicly available
      (http://www.rzpd.de) and can be used by other researchers as a digital expression
      reference.

PMID- 10958642
TI  - A quantitative evaluation of SAGE.
AB  - Serial Analysis of Gene Expression (SAGE) is an innovative technique that offers
      the potential of cataloging both the identity and relative frequencies of mRNA
      transcripts in a given poly(A(+)) RNA preparation. Although it is a very
      effective approach for determining the expression of mRNA populations, there are
      significant biases in the observed results that are inherent in the experimental
      process. These are caused by sampling error, sequencing error, nonuniqueness, and
      nonrandomness of tag sequences. The quantitative information desired from SAGE
      experiments consists of estimates of the number of genes and the frequency
      distribution of transcript copy numbers. Of additional concern is the extent to
      which a given tag sequence can be assumed to be unique to its gene. The present
      study takes these mathematical biases into account and presents a basis for
      maximum likelihood estimation of gene number and transcript copy frequencies
      given a set of experimental results. These estimates of the true state of genomic
      expression are markedly different from those based directly on the observations
      from the underlying experiments. It also is shown that while in many cases it is
      probable that a given tag sequence is unique within the genome, in larger genomes
      this cannot be safely assumed.

PMID- 10958643
TI  - Determination of single-nucleotide polymorphisms by real-time pyrophosphate DNA
      sequencing.
AB  - The characterization of naturally occurring variations in the human genome has
      evoked an immense interest during recent years. Variations known as biallelic
      Single-Nucleotide Polymorphisms (SNPs) have become increasingly popular markers
      in molecular genetics because of their wide application both in evolutionary
      relationship studies and in the identification of susceptibility to common
      diseases. We have addressed the issue of SNP genotype determination by
      investigating variations within the Renin-Angiotensin-Aldosterone System (RAAS)
      using pyrosequencing, a real-time pyrophosphate detection technology. The method
      is based on indirect luminometric quantification of the pyrophosphate that is
      released as a result of nucleotide incorporation onto an amplified template. The
      technical platform employed comprises a highly automated sequencing instrument
      that allows the analysis of 96 samples within 10 to 20 minutes. In addition to
      each studied polymorphic position, 5-10 downstream bases were sequenced for
      acquisition of reference signals. Evaluation of pyrogram data was accomplished by
      comparison of peak heights, which are proportional to the number of incorporated
      nucleotides. Analysis of the pyrograms that resulted from alternate allelic
      configurations for each addressed SNP revealed a highly discriminating pattern.
      Homozygous samples produced clear-cut single base peaks in the expected position,
      whereas heterozygous counterparts were characterized by distinct half-height
      peaks representing both allelic positions. Whenever any of the allelic bases of
      an SNP formed a homopolymer with adjacent bases, the nonallelic signal was added
      to those of the SNP. This feature did not, however, influence SNP readability.
      Furthermore, the multibase reading capacity of the described system provides
      extensive flexibility in regard to the positioning of sequencing primers and
      allows the determination of several closely located SNPs in a single run.

PMID- 10958644
TI  - Expression-based genetic/physical maps of single-nucleotide polymorphisms
      identified by the cancer genome anatomy project.
AB  - SNPs (Single-Nucleotide Polymorphisms), the most common DNA variant in humans,
      represent a valuable resource for the genetic analysis of cancer and other
      illnesses. These markers may be used in a variety of ways to investigate the
      genetic underpinnings of disease. In gene-based studies, the correlations between
      allelic variants of genes of interest and particular disease states are assessed.
      An extensive collection of SNP markers may enable entire molecular pathways
      regulating cell metabolism, growth, or differentiation to be analyzed by this
      approach. In addition, high-resolution genetic maps based on SNPs will greatly
      facilitate linkage analysis and positional cloning. The National Cancer
      Institute's CGAP-GAI (Cancer Genome Anatomy Project Genetic Annotation
      Initiative) group has identified 10,243 SNPs by examining publicly available EST
      (Expressed Sequence Tag) chromatograms. More than 6800 of these polymorphisms
      have been placed on expression-based integrated genetic/physical maps. In
      addition to a set of comprehensive SNP maps, we have produced maps containing
      single nucleotide polymorphisms in genes expressed in breast, colon, kidney,
      liver, lung, or prostate tissue. The integrated maps, a SNP search engine, and a
      Java-based tool for viewing candidate SNPs in the context of EST assemblies can
      be accessed via the CGAP-GAI web site (http://cgap.nci.nih.gov/GAI/). Our SNP
      detection tools are available to the public for noncommercial use.

PMID- 10958645
TI  - Identification of TNFRSF1B as a novel modifier gene in familial combined
      hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is the most commonly inherited
      hyperlipidemia in man, with a frequency of +/-1% in the general population and
      approximately 10% in myocardial infarction survivors. A genomic scan in 18 Dutch
      FCHL families resulted in the identification of several loci with evidence for
      linkage. One of these regions, 1p36.2, contains TNFRSF1B which encodes one of the
      tumor necrosis factor receptors. An intron 4 polymorphic CA-repeat was used to
      confirm linkage to FCHL. Linear regression analysis using 79 independent sib
      pairs showed linkage with a quantitative FCHL discriminant function (P = 0.032),
      and, borderline, with apolipoprotein B levels (P = 0.064). Furthermore, in a case
      control study, association was demonstrated since the overall CA-repeat genotype
      distribution was significantly different among 40 unrelated FCHL patients and 48
      unrelated healthy spouse controls (P = 0.029). This difference was due to a
      significant increase in allele CA271 homozygotes in the FCHL patients (P =
      0.019). Mutation analysis of exon 6 in 73 FCHL family members demonstrated the
      presence of a single nucleotide polymorphism with two alleles, coding for
      methionine (196M) and arginine (196R). Complete linkage disequilibrium between
      CA267, CA271 and CA273 and this polymorphism was detected. In 85 hyperlipidemic
      FCHL subjects, an association was demonstrated between soluble TNFRSF1B plasma
      concentrations and the CA271-196M haplotype. In conclusion, TNFRSF1B was found to
      be associated with susceptibility to FCHL. Our data suggest that an as yet
      unknown disease-associated mutation, linked to alleles 196M and CA271, plays a
      role in the pathophysiology of FCHL.

PMID- 10958646
TI  - Targeted disruption of the human LIT1 locus defines a putative imprinting control
      element playing an essential role in Beckwith-Wiedemann syndrome.
AB  - Human chromosome 11p15.5 harbors an intriguing imprinted gene cluster of 1 Mb.
      This imprinted domain is implicated in a wide variety of malignancies and
      Beckwith-Wiedemann syndrome (BWS). Recently, several lines of evidence have
      suggested that the BWS-associated imprinting cluster consists of separate
      chromosomal domains. We have previously identified LIT1, a paternally expressed
      antisense RNA within the KvLQT1 locus through a positional screening approach
      using human monochromosomal hybrids. KvLQT1 encompasses the translocation
      breakpoint cluster in BWS and patients exhibit frequent loss of maternal
      methylation at the LIT1 CpG island, implying a regulatory role for the LIT1 locus
      in coordinate control of the imprinting cluster. Here we generated modified human
      chromosomes carrying a targeted deletion of the LIT1 CpG island using
      recombination-proficient chicken DT40 cells. Consistent with the prediction, this
      mutation abolished LIT1 expression on the paternal chromosome, accompanied by
      activation of the normally silent paternal alleles of multiple imprinted loci at
      the centromeric domain including KvLQT1 and p57(KIP2). The deletion had no effect
      on imprinting of H19 located at the telomeric end of the cluster. Our findings
      demonstrate that the LIT1 CpG island can act as a negative regulator in cis for
      coordinate imprinting at the centromeric domain, thereby suggesting a role for
      the LIT1 locus in a BWS pathway leading to functional inactivation of p57(KIP2).
      Thus, the targeting and precise modification of human chromosomal alleles using
      the DT40 cell shuttle system can be used to define regulatory elements that
      confer long-range control of gene activity within chromosomal domains.

PMID- 10958647
TI  - Identification of a novel protein interacting with RPGR.
AB  - A novel protein, called RPGRIP, has been identified as interacting with the RPGR
      protein, which is mutated in a severe form of human retinal degeneration, X
      linked retinitis pigmentosa (RP3 type). The bovine RPGRIP was identified
      initially by screening for RPGR-interacting proteins with a bovine retina cDNA
      library using the yeast two-hybrid system. The specificity of the interaction was
      confirmed by co-immunoprecipitation of in vitro translated protein and using RPGR
      mutants. The human RPGRIP gene was isolated and shown to be expressed in retina
      and testis. Human RPGRIP spans a genomic interval of 34 kb, and consists of 15
      exons, some of which are alternatively spliced. It was mapped using
      monochromosomal and radiation hybrid cell lines to chromosomal region 14q11. The
      function of RPGRIP is unknown; it shows no homology to proteins of known
      function, although it is predicted to form two coiled-coil domains at the N
      terminus. RPGRIP is a strong candidate gene for causing human retinal
      degeneration.

PMID- 10958648
TI  - The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport
      like proteins in the outer segments of rod photoreceptors.
AB  - Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene cause X-linked
      retinitis pigmentosa type 3 (RP3), a severe, progressive and degenerative retinal
      dystrophy eventually leading to complete blindness. RPGR is ubiquitously
      expressed, yet mutations in the RPGR gene lead to a retina-restricted phenotype.
      To date, all RP3 associated missense mutations that have been identified are
      located in the RCC1-homologous domain (RHD) of RPGR. To investigate the molecular
      pathogenesis of RP3, we screened retinal yeast two-hybrid libraries with the RHD
      of RPGR. We identified several alternatively spliced gene products, some with
      retina-restricted expression, that interact specifically with RPGR in vivo and in
      vitro. Thus, these proteins were named RPGR-interacting protein 1 (RPGRIP1)
      isoforms. They contain a C-terminal RPGR-interacting domain and stretches of
      variable coiled-coil domains homologous to proteins involved in vesicular
      trafficking. The interaction between RPGR and RPGRIP1 isoforms was impaired in
      vivo by RP3-associated mutations in RPGR. Moreover, RPGR and RPGRIP1 co-localize
      in the outer segment of rod photoreceptors, which is in full agreement with the
      retinitis pigmentosa phenotype observed in RP3 patients. The localization of
      RPGRIP1 at 14q11 makes it a strong candidate gene for RP16. These results provide
      a clue for the retina-specific pathogenesis in RP3, and hint towards the
      involvement of RPGR and RPGRIP1 in mediating vesicular transport-associated
      processes.

PMID- 10958649
TI  - Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor
      cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome
      8q21.
AB  - Achromatopsia is an autosomal recessive disorder featuring total colour
      blindness, photophobia, reduced visual acuity and nystagmus. While mutations in
      the CNGA3 gene on chromosome 2q11 are responsible for achromatopsia in a subset
      of patients, previous linkage studies have localized another achromatopsia locus,
      ACHM3, on chromosome 8q21. Using achromatopsia families in which CNGA3 mutations
      have been excluded, we refined the ACHM3 locus to a 3.7 cM region enclosed by
      markers D8S1838 and D8S273. Two yeast artificial chromosome (YAC) contigs
      covering nearly the entire ACHM3 interval were constructed. Database searches
      with YAC content sequences identified two overlapping high throughput genomic
      sequencing phase (HTGS) entries which contained sequences homologous to the
      murine cng6 gene encoding the putative beta-subunit of the cone photoreceptor
      cGMP-gated channel. Using RT-PCR and RACE, we identified and cloned the human
      cDNA homologue, designated CNGB3, which encodes an 809 amino acid polypeptide.
      Northern blot analysis revealed a major transcript of approximately 4.4 kb
      specifically expressed in the retina. The human CNGB3 gene consists of 18 exons
      distributed over approximately 200 kb of genomic sequence. Analysis of the CNGB3
      gene in achromats revealed six different mutations including a missense mutation
      (S435F), two stop codon mutations (R203X and E336X), a 1 bp and an 8 bp deletion
      (1148delC and 819-826del) and a putative splice site mutation of intron 13. The
      1148delC mutation was identified recurrently in several families, and in total
      was present on 11 of 22 disease chromosomes segregating in our families.

PMID- 10958650
TI  - An evolutionarily conserved germ cell-specific hnRNP is encoded by a
      retrotransposed gene.
AB  - The gene encoding heterogeneous ribonucleoprotein (hnRNP) G recently has been
      mapped to the X chromosome. All mammals have a Y chromosome-encoded homologue of
      HNRNP G called RBMY, which is implicated with a role in male fertility and is a
      candidate for the azoospermia factor gene. We have identified a new member of
      this gene family, HNRNP G-T, and have mapped it as a single-copy gene on
      chromosome 11. This gene contains an uninterrupted open reading frame and no
      introns, consistent with derivation from a retroposon. However, unlike many
      retroposon-derived genes, HNRNP G-T is not a pseudogene. An antiserum raised to
      the conceptual reading frame of HNRNP G-T showed that it encodes a protein that
      is highly expressed in germ cells and in particular in the nuclei of meiotic
      spermatocytes. Surprisingly, although this antiserum was raised against human
      hnRNP G-T protein, it can also detect a similar protein in the testis of several
      mammals. This suggests that the protein is highly conserved and that the
      retrotransposition event generating the HNRNP G-T gene pre-dated at least the
      common ancestor of mouse and man. The existence of an additional testis-specific
      hnRNP G family member provides evidence for the importance of these proteins in
      normal germ cell development.

PMID- 10958651
TI  - SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence
      changes may play a role in reduced penetrance.
AB  - We recently described an untranslated CTG expansion that causes a previously
      undescribed form of spinocerebellar ataxia (SCA8). The SCA8 CTG repeat is
      preceded by a polymorphic but stable CTA tract, with the configuration (CTA)(1
      21)(CTG)(n). The CTG portion of the repeat is elongated on pathogenic alleles,
      which nearly always change in size when transmitted from generation to
      generation. To better understand the reduced penetrance and maternal penetrance
      bias associated with SCA8 we analyzed the sequence configurations and instability
      patterns of the CTG repeat in affected and unaffected family members. In contrast
      to other triplet repeat diseases, expanded alleles found in affected SCA8
      individuals can have either a pure uninterrupted CTG repeat tract or an allele
      with one or more CCG, CTA, CTC, CCA or CTT interruptions. Surprisingly, we found
      six different sequence configurations of the CTG repeat on expanded alleles in a
      seven generation family. In two instances duplication of CCG interruptions
      occurred over a single generation and in other instances duplications that had
      occurred in different branches of the family could be inferred. We also evaluated
      SCA8 instability in sperm samples from individuals with expansions ranging in
      size from 80 to 800 repeats in blood. Surprisingly the SCA8 repeat tract in sperm
      underwent contractions, with nearly all of the resulting expanded alleles having
      repeat lengths of <100 CTGs, a size that is not often associated with disease.
      These en masse repeat contractions in sperm likely underlie the reduced
      penetrance associated with paternal transmission.

PMID- 10958652
TI  - Variation in residual PITX2 activity underlies the phenotypic spectrum of
      anterior segment developmental disorders.
AB  - The autosomal dominant disorders iris hypolasia (IH), iridogoniodysgenesis
      syndrome (IGDS) and Axenfeld-Rieger syndrome (ARS) are characterized by
      maldevelopment of the anterior segment of the eye associated with an increased
      risk of early-onset glaucoma. IH, IGDS and ARS are allelic disorders, as all
      three can result from mutations of the transcription factor PITX2. IH is the
      mildest of the three, whereas ARS exhibits the most severe ocular malformations.
      We hypothesize that varying amounts of residual PITX2 activity could underlie the
      severity of these phenotypes. Missense mutations of the PITX2 homeodomain
      identified in IH (Arg46Trp), IGDS (Arg31His) and ARS patients (Leu16Gln;
      Thr30Pro; Arg53Pro) were introduced into recombinant PITX2 cDNA by site-directed
      mutagenesis. PITX2 mutant proteins expressed in COS-7 cells were determined to be
      stable and localized to the nucleus; however, the Arg53Pro ARS mutant also
      displayed cytoplasmic staining. Our findings are consistent with the possibility
      of a novel nuclear localization signal (NLS) within helix 3 of the PITX2
      homeodomain, homologous to the NLS of the related transcription factor PDX-1.
      Analysis of the five mutant PITX2 proteins by DNA-binding shifts and
      transactivation studies demonstrated reduced activity of the IH and IGDS mutant
      PITX2 proteins, with the IH mutant retaining the most activity in both studies,
      whereas the ARS mutant PITX2 proteins proved to be non-functional. In addition to
      providing insight into the etiological mechanism of IH, IGDS and ARS, these
      results are consistent with the hypothesis that mutant PITX2 proteins that retain
      partial function result in milder anterior segment aberrations.

PMID- 10958653
TI  - Myotilin is mutated in limb girdle muscular dystrophy 1A.
AB  - We have identified a mutation in the myotilin gene in a large North American
      family of German descent expressing an autosomal dominant form of limb girdle
      muscular dystrophy (LGMD1A). We have previously mapped this gene to 5q31.
      Symptoms of this adult onset disease are progressive weakness of the hip and
      shoulder girdles, as well as a distinctive dysarthric pattern of speech. Muscle
      of affected individuals shows degeneration of myofibers, variations in fiber
      size, fiber splitting, centrally located myonuclei and a large number of
      autophagic vesicles. Affected muscle also exhibits disorganization and streaming
      of the Z-line similar to that seen in nemaline myopathy. We have identified a
      C450T missense mutation in the myotilin gene that is predicted to result in the
      conversion of residue 57 from threonine to isoleucine. This mutation has not been
      found in 396 control chromosomes. The mutant allele is transcribed and normal
      levels of correctly localized myotilin protein are seen in LGMD1A muscle.
      Myotilin is a sarcomeric protein that binds to alpha-actinin and is localized in
      the Z-line. The observed missense mutation does not disrupt binding to alpha
      actinin.

PMID- 10958654
TI  - Clinical, biochemical and molecular genetic correlations in adenylosuccinate
      lyase deficiency.
AB  - Adenylosuccinate lyase (ADSL) deficiency (MIM 103050) is an autosomal recessive
      inborn error of purine synthesis characterized by the accumulation in body fluids
      of succinylaminoimidazolecarboxamide (SAICA) riboside and succinyladenosine (S
      Ado), the dephosphorylated derivatives of the two substrates of the enzyme.
      Because ADSL-deficient patients display widely variable degrees of psychomotor
      retardation, we have expressed eight mutated ADSL enzymes as thioredoxin fusions
      and compared their properties with the clinical and biochemical characteristics
      of 10 patients. Three expressed mutated ADSL enzymes (M26L, R426H and T450S) were
      thermolabile, four (A2V, R141W, R303C and S395R) were thermostable and one
      (del206-218), was inactive. Thermolabile mutations decreased activities with
      SAICA ribotide (SAICAR) and adenylosuccinate (S-AMP) in parallel, or more with
      SAICAR than with S-AMP. Patients homozygous for one of these mutations, R426H,
      displayed similarly decreased ADSL activities in their fibroblasts, S-Ado:SAICA
      riboside ratios of approximately 1 in their cerebrospinal fluid and were
      profoundly retarded. With the exception of A2V, thermostable mutations decreased
      activity with S-AMP to a much more marked extent than with SAICAR. Two unrelated
      patients homozygous for one of the thermostable mutations, R303C, also displayed
      a much more marked decrease in the activity of fibroblast ADSL with S-AMP than
      with SAICAR, had S-Ado:SAICA riboside ratios between 3 and 4 in their
      cerebrospinal fluid and were mildly retarded. These results suggest that, in some
      cases, the genetic lesion of ADSL determines the ratio of its activities with S
      AMP versus SAICAR, which in turn defines the S-Ado:SAICA riboside ratio and the
      patients' mental status.

PMID- 10958655
TI  - Characterization of a monoclonal antibody panel shows that the myotonic dystrophy
      protein kinase, DMPK, is expressed almost exclusively in muscle and heart.
AB  - Myotonic dystrophy (DM) is a multisystemic disorder caused by an inherited CTG
      repeat expansion which affects three genes encoding the DM protein kinase (DMPK),
      a homeobox protein Six5 and a protein containing WD repeats. Using a panel of 16
      monoclonal antibodies against several different DMPK epitopes we detected DMPK,
      as a single protein of approximately 80 kDa, only in skeletal muscle, cardiac
      muscle and, to a lesser extent, smooth muscle. Many earlier reports of DMPK with
      different sizes and tissue distributions appear to be due to antibody cross
      reactions with more abundant proteins. One such antibody, MANDM1, was used to
      isolate two related protein kinases, MRCK alpha and beta, from a human brain cDNA
      library and the shared epitope was located at the catalytic site of DMPK using a
      phage-displayed random peptide library. The peptide library also identified an
      epitope shared between DMPK and a 55 kDa muscle-specific protein. The results
      suggest that effects of the repeat expansion on the DMPK gene may be responsible
      for muscle and heart features of DM, whereas clinical changes in other tissues
      may be due to effects on the other two genes.

PMID- 10958656
TI  - Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill
      genetic criteria for direct involvement in Huntington's disease pathogenesis.
AB  - An elongated glutamine tract in mutant huntingtin initiates Huntington's disease
      (HD) pathogenesis via a novel structural property that displays neuronal
      selectivity, glutamine progressivity and dominance over the normal protein based
      on genetic criteria. As this mechanism is likely to involve a deleterious protein
      interaction, we have assessed the major class of huntingtin interactors
      comprising three WW domain proteins. These are revealed to be related spliceosome
      proteins (HYPA/FBP-11 and HYPC) and a transcription factor (HYPB) that implicate
      huntingtin in mRNA biogenesis. In HD post-mortem brain, specific antibody
      reagents detect each partner in HD target neurons, in association with disease
      related N-terminal morphologic deposits but not with filter trapped insoluble
      aggregate. Glutathione S:-transferase partner 'pull-down' assays reveal soluble,
      aberrantly migrating, forms of full-length mutant huntingtin specific to HD
      target tissue. Importantly, these novel mutant species exhibit exaggerated WW
      domain binding that abrogates partner association with other huntingtin isoforms.
      Thus, each WW domain partner's association with huntingtin fulfills HD genetic
      criteria, supporting a direct role in pathogenesis. Our findings indicate that
      modification of mutant huntingtin in target neurons may promote an abnormal
      interaction with one, or all, of huntingtin's WW domain partners, perhaps
      altering ribonucleoprotein function with toxic consequences.

PMID- 10958657
TI  - Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1
      genes during spermatogenesis.
AB  - Parental-specific epigenetic modifications are imprinted on a subset of genes in
      the mammalian genome during germ cell maturation. However, the precise timing of
      their establishment remains to be determined. Methylation of CpG dinucleotides
      has been shown to be a part of the parental imprint. We have examined how the
      methylation pattern characteristic of the paternal allele in germ cells are
      established during human spermatogenesis. Two representative imprinted genes, H19
      and MEST/PEG1, were studied. The experiments were performed using the bisulphite
      sequencing method on microdissected individual cells at different stages of male
      germ cell differentiation. We show that both genes are unmethylated in fetal
      spermatogonia, suggesting that all pre-existing methylation imprints are already
      erased by this stage. The MEST/PEG1 gene remains unmethylated at all subsequent
      post-pubertal stages of spermatogenesis, including mature spermatozoa. The
      methylation of H19 typical of the paternal allele first appears in a subset of
      adult spermatogonia and then is maintained in spermatocytes, spermatids and
      mature spermatozoa. Our results suggest that the methylation imprint inherited
      from the parents is first erased in the male germ line at an early fetal stage.
      The paternal-specific imprint is re-established only later, during spermatogonial
      differentiation in the adult testis.

PMID- 10958658
TI  - Mariner is defective in myosin VIIA: a zebrafish model for human hereditary
      deafness.
AB  - The zebrafish (Danio rerio) possesses two mechanosensory organs believed to be
      homologous to each other: the inner ear, which is responsible for the senses of
      audition and equilibrium, and the lateral line organ, which is involved in the
      detection of water movements. Eight zebrafish circler or auditory/vestibular
      mutants appear to have defects specific to sensory hair cell function. The
      circler genes may therefore encode components of the mechanotransduction
      apparatus and/or be the orthologous counterparts of the genes underlying human
      hereditary deafness. In this report, we show that the phenotype of the circler
      mutant, mariner, is due to mutations in the gene encoding Myosin VIIA, an
      unconventional myosin which is expressed in sensory hair cells and is responsible
      for various types of hearing disorder in humans, namely Usher 1B syndrome, DFNB2
      and DFNA11. Our analysis of the fine structure of hair bundles in the mariner
      mutants suggests that a missense mutation within the C-terminal FERM domain of
      the tail of Myosin VIIA has the potential to dissociate the two different
      functions of the protein in hair bundle integrity and apical endocytosis.
      Notably, mariner sensory hair cells display morphological and functional defects
      that are similar to those present in mouse shaker-1 hair cells which are
      defective in Myosin VIIA. Thus, this study demonstrates the striking conservation
      of the function of Myosin VIIA throughout vertebrate evolution and establishes
      mariner as the first fish model for human hereditary deafness.

PMID- 10958659
TI  - CREB-binding protein sequestration by expanded polyglutamine.
AB  - Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited
      neurodegenerative diseases known to be caused by CAG repeat expansion. The
      expansion results in an expanded polyglutamine tract, which likely confers a
      novel, toxic function to the affected protein. Cell culture and transgenic mouse
      studies have implicated the nucleus as a site for pathogenesis, suggesting that a
      critical nuclear factor or process is disrupted by the polyglutamine expansion.
      In this report we present evidence that CREB-binding protein (CBP), a
      transcriptional co-activator that orchestrates nuclear response to a variety of
      cell signaling cascades, is incorporated into nuclear inclusions formed by
      polyglutamine-containing proteins in cultured cells, transgenic mice and tissue
      from patients with SBMA. We also show CBP incorporation into nuclear inclusions
      formed in a cell culture model of another polyglutamine disease, spinocerebellar
      ataxia type 3. We present evidence that soluble levels of CBP are reduced in
      cells expressing expanded polyglutamine despite increased levels of CBP mRNA.
      Finally, we demonstrate that over-expression of CBP rescues cells from
      polyglutamine-mediated toxicity in neuronal cell culture. These data support a
      CBP-sequestration model of polyglutamine expansion disease.

PMID- 10958660
TI  - Involvement of retinoblastoma protein and HBP1 in histone H1(0) gene expression.
AB  - The histone H1(0)-encoding gene is expressed in vertebrates in differentiating
      cells during the arrest of proliferation. In the H1(0) promoter, a specific
      regulatory element, which we named the H4 box, exhibits features which implicate
      a role in mediating H1(0) gene expression in response to both differentiation and
      cell cycle control signals. For instance, within the linker histone gene family,
      the H4 box is found only in the promoters of differentiation-associated subtypes,
      suggesting that it is specifically involved in differentiation-dependent
      expression of these genes. In addition, an element nearly identical to the H4 box
      is conserved in the promoters of histone H4-encoding genes and is known to be
      involved in their cell cycle-dependent expression. The transcription factors
      interacting with the H1(0) H4 box were therefore expected to link differentiation
      dependent expression of H1(0) to the cell cycle control machinery. The aim of
      this work was to identify such transcription factors and to obtain information
      concerning the regulatory pathway involved. Interestingly, our cloning strategy
      led to the isolation of a retinoblastoma protein (RB) partner known as HBP1.
      HBP1, a high-mobility group box transcription factor, interacted specifically
      with the H1(0) H4 box and moreover was expressed in a differentiation-dependent
      manner. We also showed that the HBP1-encoding gene is able to produce different
      forms of HBP1. Finally, we demonstrated that both HBP1 and RB were involved in
      the activation of H1(0) gene expression. We therefore propose that HBP1 mediates
      a link between the cell cycle control machinery and cell differentiation signals.
      Through modulating the expression of specific chromatin-associated proteins such
      as histone H1(0), HBP1 plays a vital role in chromatin remodeling events during
      the arrest of cell proliferation in differentiating cells.

PMID- 10958661
TI  - The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of
      IkappaB kinase and c-Jun N-terminal kinase.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2
      ligand [Apo2L]) is a member of the TNF superfamily and has been shown to have
      selective antitumor activity. Although it is known that TRAIL (Apo2L) induces
      apoptosis and activates NF-kappaB and Jun N-terminal kinase (JNK) through
      receptors such as TRAIL-R1 (DR4) and TRAIL-R2 (DR5), the components of its
      signaling cascade have not been well defined. In this report, we demonstrated
      that the death domain kinase RIP is essential for TRAIL-induced IkappaB kinase
      (IKK) and JNK activation. We found that ectopic expression of the dominant
      negative mutant RIP, RIP(559-671), blocks TRAIL-induced IKK and JNK activation.
      In the RIP null fibroblasts, TRAIL failed to activate IKK and only partially
      activated JNK. The endogenous RIP protein was detected by immunoprecipitation in
      the TRAIL-R1 complex after TRAIL treatment. More importantly, we found that RIP
      is not involved in TRAIL-induced apoptosis. In addition, we also demonstrated
      that the TNF receptor-associated factor 2 (TRAF2) plays little role in TRAIL
      induced IKK activation although it is required for TRAIL-mediated JNK activation.
      These results indicated that the death domain kinase RIP, a key factor in TNF
      signaling, also plays a pivotal role in TRAIL-induced IKK and JNK activation.

PMID- 10958662
TI  - Meiotic segregation, synapsis, and recombination checkpoint functions require
      physical interaction between the chromosomal proteins Red1p and Hop1p.
AB  - In yeast, HOP1 and RED1 are required during meiosis for proper chromosome
      segregation and the consequent formation of viable spores. Mutations in either
      HOP1 or RED1 create unique as well as overlapping phenotypes, indicating that the
      two proteins act alone as well as in concert with each other. To understand which
      meiotic processes specifically require Red1p-Hop1p hetero-oligomers, a novel
      genetic screen was used to identify a single-point mutation of RED1, red1-K348E,
      that separates Hop1p binding from Red1p homo-oligomerization. The Red1-K348E
      protein is stable, phosphorylated in a manner equivalent to Red1p, and undergoes
      efficient homo-oligomerization; however, its ability to interact with Hop1p both
      by two-hybrid and coimmunoprecipitation assays is greatly reduced. Overexpression
      of HOP1 specifically suppresses red1-K348E, supporting the idea that the only
      defect in the protein is a reduced affinity for Hop1p. red1-K348E mutants exhibit
      reduced levels of crossing over and spore viability and fail to undergo
      chromosome synapsis, thereby implicating a role for Red1p-Hop1p hetero-oligomers
      in these processes. Furthermore, red1-K348E suppresses the sae2/com1 defects in
      meiotic progression and sporulation, indicating a previously unknown role for
      HOP1 in the meiotic recombination checkpoint.

PMID- 10958663
TI  - trans splicing of polycistronic Caenorhabditis elegans pre-mRNAs: analysis of the
      SL2 RNA.
AB  - Genes in Caenorhabditis elegans operons are transcribed as polycistronic pre
      mRNAs in which downstream gene products are trans spliced to a specialized
      spliced leader, SL2. SL2 is donated by a 110-nucleotide RNA, SL2 RNA, present in
      the cell as an Sm-bound snRNP. SL2 RNA can be conceptually folded into a
      phylogenetically conserved three-stem-loop secondary structure. Here we report an
      in vivo mutational analysis of the SL2 RNA. Some sequences can be changed without
      consequence, while other changes result in a substantial loss of trans splicing.
      Interestingly, the spliced leader itself can be dramatically altered, such that
      the first stem-loop cannot form, with only a relatively small loss in trans
      splicing efficiency. However, the primary sequence of stem II is crucial for SL2
      trans splicing. Similarly, the conserved primary sequence of the third stem-loop
      plays a key role in trans splicing. While mutations in stem-loop III allow snRNP
      formation, a single nucleotide substitution in the loop prevents trans splicing.
      In contrast, the analogous region of SL1 RNA is not highly conserved, and its
      mutation does not abrogate function. Thus, stem-loop III appears to confer a
      specific function to SL2 RNA. Finally, an upstream sequence, previously predicted
      to be a proximal sequence element, is shown to be required for SL2 RNA
      expression.

PMID- 10958664
TI  - Preferential accessibility of the yeast his3 promoter is determined by a general
      property of the DNA sequence, not by specific elements.
AB  - Yeast promoter regions are often more accessible to nuclear proteins than are
      nonpromoter regions. As assayed by HinfI endonuclease cleavage in living yeast
      cells, HinfI sites located in the promoters of all seven genes tested were 5- to
      20-fold more accessible than sites in adjacent nonpromoter regions. HinfI
      hypersensitivity within the his3 promoter region is locally determined, since it
      was observed when this region was translocated to the middle of the ade2
      structural gene. Detailed analysis of the his3 promoter indicated that
      preferential accessibility is not determined by specific elements such as the
      Gcn4 binding site, poly(dA-dT) sequences, TATA elements, or initiator elements or
      by transcriptional activity. However, progressive deletion of the promoter region
      in either direction resulted in a progressive loss of HinfI accessibility.
      Preferential accessibility is independent of the Swi-Snf chromatin remodeling
      complex, Gcn5 histone acetylase complexes Ada and SAGA, and Rad6, which
      ubiquitinates histone H2B. These results suggest that preferential accessibility
      of the his3 (and presumably other) promoter regions is determined by a general
      property of the DNA sequence (e.g., base composition or a related feature) rather
      than by defined sequence elements. The organization of the compact yeast genome
      into inherently distinct promoter and nonpromoter regions may ensure that
      transcription factors bind preferentially to appropriate sites in promoters
      rather than to the excess of irrelevant but equally high-affinity sites in
      nonpromoter regions.

PMID- 10958665
TI  - Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant
      negative mutation of HEB.
AB  - Lymphocyte development and differentiation are regulated by the basic helix-loop
      helix (bHLH) transcription factors encoded by the E2A and HEB genes. These bHLH
      proteins bind to E-box enhancers in the form of homodimers or heterodimers and,
      consequently, activate transcription of the target genes. E2A homodimers are the
      predominant bHLH proteins present in B-lineage cells and are shown genetically to
      play critical roles in B-cell development. E2A-HEB heterodimers, the major bHLH
      dimers found in thymocyte extracts, are thought to play a similar role in T-cell
      development. However, disruption of either the E2A or HEB gene led to only
      partial blocks in T-cell development. The exact role of E2A-HEB heterodimers and
      possibly the E2A and HEB homodimers in T-cell development cannot be distinguished
      in simple disruption analysis due to a functional compensation from the residual
      bHLH homodimers. To further define the function of E2A-HEB heterodimers, we
      generated and analyzed a dominant negative allele of HEB, which produces a
      physiological amount of HEB proteins capable of forming nonfunctional
      heterodimers with E2A proteins. Mice carrying this mutation show a stronger and
      earlier block in T-cell development than HEB complete knockout mice. The
      developmental block is specific to the alpha/beta T-cell lineage at a stage
      before the completion of V(D)J recombination at the TCRbeta gene locus. This
      defect is intrinsic to the T-cell lineage and cannot be rescued by expression of
      a functional T-cell receptor transgene. These results indicate that E2A-HEB
      heterodimers play obligatory roles both before and after TCRbeta gene
      rearrangement during the alpha/beta lineage T-cell development.

PMID- 10958667
TI  - DNA excision repair and DNA damage-induced apoptosis are linked to Poly(ADP
      ribosyl)ation but have different requirements for p53.
AB  - Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that
      catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different
      chromatin constituents, forming branched ADP-ribose polymers. The enzymatic
      activity of PARP is induced upon DNA damage and the PARP protein is cleaved
      during apoptosis, which suggested a role of PARP in DNA repair and DNA damage
      induced cell death. We have generated transgenic mice that lack PARP activity in
      thymocytes owing to the targeted expression of a dominant negative form of PARP.
      In the presence of single-strand DNA breaks, the absence of PARP activity
      correlated with a strongly increased rate of apoptosis compared to cells with
      intact PARP activity. We found that blockage of PARP activity leads to a drastic
      increase of p53 expression and activity after DNA damage and correlates with an
      accelerated onset of Bax expression. DNA repair is almost completely blocked in
      PARP-deficient thymocytes regardless of p53 status. We found the same increased
      susceptibility to apoptosis in PARP null mice, a similar inhibition of DNA repair
      kinetics, and the same upregulation of p53 in response to DNA damage. Thus, based
      on two different experimental in vivo models, we identify a direct, p53
      independent, functional connection between poly(ADP-ribosyl)ation and the DNA
      excision repair machinery. Furthermore, we propose a p53-dependent link between
      PARP activity and DNA damage-induced cell death.

PMID- 10958666
TI  - A homolog of voltage-gated Ca(2+) channels stimulated by depletion of secretory
      Ca(2+) in yeast.
AB  - In animal cells, capacitative calcium entry (CCE) mechanisms become activated
      specifically in response to depletion of calcium ions (Ca(2+)) from secretory
      organelles. CCE serves to replenish those organelles and to enhance signaling
      pathways that respond to elevated free Ca(2+) concentrations in the cytoplasm.
      The mechanism of CCE regulation is not understood because few of its essential
      components have been identified. We show here for the first time that the budding
      yeast Saccharomyces cerevisiae employs a CCE-like mechanism to refill Ca(2+)
      stores within the secretory pathway. Mutants lacking Pmr1p, a conserved Ca(2+)
      pump in the secretory pathway, exhibit higher rates of Ca(2+) influx relative to
      wild-type cells due to the stimulation of a high-affinity Ca(2+) uptake system.
      Stimulation of this Ca(2+) uptake system was blocked in pmr1 mutants by
      expression of mammalian SERCA pumps. The high-affinity Ca(2+) uptake system was
      also stimulated in wild-type cells overexpressing vacuolar Ca(2+) transporters
      that competed with Pmr1p for substrate. A screen for yeast mutants specifically
      defective in the high-affinity Ca(2+) uptake system revealed two genes, CCH1 and
      MID1, previously implicated in Ca(2+) influx in response to mating pheromones.
      Cch1p and Mid1p were localized to the plasma membrane, coimmunoprecipitated from
      solubilized membranes, and shown to function together within a single pathway
      that ensures that adequate levels of Ca(2+) are supplied to Pmr1p to sustain
      secretion and growth. Expression of Cch1p and Mid1p was not affected in pmr1
      mutants. The evidence supports the hypothesis that yeast maintains a homeostatic
      mechanism related to CCE in mammalian cells. The homology between Cch1p and the
      catalytic subunit of voltage-gated Ca(2+) channels raises the possibility that in
      some circumstances CCE in animal cells may involve homologs of Cch1p and a
      conserved regulatory mechanism.

PMID- 10958668
TI  - Characterization of the role of AMP-activated protein kinase in the regulation of
      glucose-activated gene expression using constitutively active and dominant
      negative forms of the kinase.
AB  - In the liver, glucose induces the expression of a number of genes involved in
      glucose and lipid metabolism, e.g., those encoding L-type pyruvate kinase and
      fatty acid synthase. Recent evidence has indicated a role for the AMP-activated
      protein kinase (AMPK) in the inhibition of glucose-activated gene expression in
      hepatocytes. It remains unclear, however, whether AMPK is involved in the glucose
      induction of these genes. In order to study further the role of AMPK in
      regulating gene expression, we have generated two mutant forms of AMPK. One of
      these (alpha1(312)) acts as a constitutively active kinase, while the other
      (alpha1DN) acts as a dominant negative inhibitor of endogenous AMPK. We have used
      adenovirus-mediated gene transfer to express these mutants in primary rat
      hepatocytes in culture in order to determine their effect on AMPK activity and
      the transcription of glucose-activated genes. Expression of alpha1(312) increased
      AMPK activity in hepatocytes and blocked completely the induction of a number of
      glucose-activated genes in response to 25 mM glucose. This effect is similar to
      that observed following activation of AMPK by 5-amino-imidazolecarboxamide
      riboside. Expression of alpha1DN markedly inhibited both basal and stimulated
      activity of endogenous AMPK but had no effect on the transcription of glucose
      activated genes. Our results suggest that AMPK is involved in the inhibition of
      glucose-activated gene expression but not in the induction pathway. This study
      demonstrates that the two mutants we have described will provide valuable tools
      for studying the wider physiological role of AMPK.

PMID- 10958669
TI  - Yeast glycogen synthase kinase 3 is involved in protein degradation in
      cooperation with Bul1, Bul2, and Rsp5.
AB  - The yeast Saccharomyces cerevisiae has four genes, MCK1, MDS1 (RIM11), MRK1, and
      YOL128c, that encode glycogen synthase kinase 3 (GSK-3) homologs. The gsk-3 null
      mutant, in which these four genes are disrupted, shows temperature sensitivity,
      which is suppressed by the expression of mammalian GSK-3beta and by an osmotic
      stabilizer. Suppression of temperature sensitivity by an osmotic stabilizer is
      also observed in the bul1 bul2 double null mutant, and the temperature
      sensitivity of the bul1 bul2 double null mutant is suppressed by multiple copies
      of MCK1. We have screened rog mutants (revertants of gsk-3) which suppress the
      temperature sensitivity of the mck1 mds1 double null mutant and found that two of
      them, rog1 and rog2, also suppress the temperature sensitivity of the bul1 bul2
      double null mutant. Bul1 and Bul2 have been reported to bind to Rsp5, a hect (for
      homologous to E6-associated-protein carboxyl terminus)-type ubiquitin ligase, but
      involvement of Bul1 and Bul2 in protein degradation has not been demonstrated. We
      find that Rog1, but not Rog2, is stabilized in the gsk-3 null and the bul1 bul2
      double null mutants. Rog1 binds directly to Rsp5, and their interaction is
      dependent on GSK-3. Furthermore, Rog1 is stabilized in the npi1 mutant, in which
      RSP5 expression levels are reduced. These results suggest that yeast GSK-3
      regulates the stability of Rog1 in cooperation with Bul1, Bul2, and Rsp5.

PMID- 10958670
TI  - HCF-1 amino- and carboxy-terminal subunit association through two separate sets
      of interaction modules: involvement of fibronectin type 3 repeats.
AB  - When herpes simplex virus infects permissive cells, the viral regulatory protein
      VP16 forms a specific complex with HCF-1, a preexisting nuclear protein involved
      in cell proliferation. The majority of HCF-1 in the cell is a complex of
      associated amino (HCF-1(N))- and carboxy (HCF-1(C))-terminal subunits that result
      from an unusual proteolytic processing of a large precursor polypeptide. Here, we
      have characterized the structure and function of sequences required for HCF-1(N)
      and HCF-1(C) subunit association. HCF-1 contains two matched pairs of self
      association sequences called SAS1 and SAS2. One of these matched association
      sequences, SAS1, consists of a short 43-amino-acid region of the HCF-1(N)
      subunit, which associates with a carboxy-terminal region of the HCF-1(C) subunit
      that is composed of a tandem pair of fibronectin type 3 repeats, a structural
      motif known to promote protein-protein interactions. Unexpectedly, the related
      protein HCF-2, which is not proteolyzed, also contains a functional SAS1
      association element, suggesting that this element does not function solely to
      maintain HCF-1(N) and HCF-1(C) subunit association. HCF-1(N) subunits do not
      possess a nuclear localization signal. We show that, owing to a carboxy-terminal
      HCF-1 nuclear localization signal, HCF-1(C) subunits can recruit HCF-1(N)
      subunits to the nucleus.

PMID- 10958671
TI  - Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation
      and release of cytochrome c from mitochondria.
AB  - BAP31 is a 28-kDa integral membrane protein of the endoplasmic reticulum whose
      cytosolic domain contains two identical caspase recognition sites (AAVD.G) that
      are preferentially cleaved by initiator caspases, including caspase 8. Cleavage
      of BAP31 during apoptosis generates a p20 fragment that remains integrated in the
      membrane and, when expressed ectopically, is a potent inducer of cell death. To
      examine the consequences of maintaining the structural integrity of BAP31 during
      apoptosis, the caspase recognition aspartate residues were mutated to alanine
      residues, and Fas-mediated activation of caspase 8 and cell death were examined
      in human KB epithelial cells stably expressing the caspase-resistant mutant
      crBAP31. crBAP31 only modestly slowed the time course for activation of caspases,
      as assayed by the processing of procaspases 8 and 3 and the measurement of total
      DEVDase activity. As a result, cleavage of the caspase targets poly(ADP-ribosyl)
      polymerase and endogenous BAP31, as well as the redistribution of
      phosphatidylserine and fragmentation of DNA, was observed. In contrast,
      cytoplasmic membrane blebbing and fragmentation and apoptotic redistribution of
      actin were strongly inhibited, cell morphology was retained near normal, and the
      irreversible loss of cell growth potential following removal of the Fas stimulus
      was delayed. Of note, crBAP31-expressing cells also resisted Fas-mediated release
      of cytochrome c from mitochondria, and the mitochondrial electrochemical
      potential was only partly reduced. These results argue that BAP31 cleavage is
      important for manifesting cytoplasmic apoptotic events associated with membrane
      fragmentation and reveal an unexpected cross talk between mitochondria and the
      endoplasmic reticulum during Fas-mediated apoptosis in vivo.

PMID- 10958672
TI  - Uncoupling between phenotypic senescence and cell cycle arrest in aging p21
      deficient fibroblasts.
AB  - Irreversible G(1) arrest in senescent human fibroblasts is mediated by two
      inhibitors of cyclin-dependent kinases (Cdks), p21(Cip1/SDI1/WAF1) and
      p16(Ink4A). To determine the physiological and molecular events that specifically
      require p21, we studied senescence in human diploid fibroblasts expressing the
      human papillomavirus type 16 E6 oncogene, which confers low p21 levels via
      enhanced p53 degradation. We show that in late-passage E6 cells, high Cdk
      activity drives the cell cycle, but population expansion is slowed down by crisis
      like events, probably owing to defective cell cycle checkpoints. At the end of
      lifespan, terminal-passage E6 cells exhibited several aspects of the senescent
      phenotype and accumulated unphosphorylated pRb and p16. However, both replication
      and cyclin-Cdk2 kinase activity were still not blocked, demonstrating that
      phenotypic and replicative senescence are uncoupled in the absence of normal p21
      levels. At this stage, E6 cells also failed to upregulate p27 and inactivate
      cyclin-Cdk complexes in response to serum deprivation. Eventually, irreversible
      G(1) arrest occurred coincident with inactivation of cyclin E-Cdk2 owing to
      association with p21. Similarly, when p21(-/-) mouse embryo fibroblasts reached
      the end of their lifespan, they had the appearance of senescent cells yet, in
      contrast to their wild-type counterparts, they were deficient in downregulating
      bromodeoxyuridine incorporation, cyclin E- and cyclin A-Cdk2 activity, and
      inhibiting pRb hyperphosphorylation. These data support the model that the
      critical event ensuring G(1) arrest in senescence is p21-dependent Cdk
      inactivation, while other aspects of senescent phenotype appear to occur
      independently of p21.

PMID- 10958673
TI  - ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the
      cis-acting element responsible for the mammalian unfolded protein response.
AB  - Transcription of genes encoding molecular chaperones and folding enzymes in the
      endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the
      ER. This intracellular signaling, known as the unfolded protein response (UPR),
      is mediated by the cis-acting ER stress response element (ERSE) in mammals. In
      addition to ER chaperones, the mammalian transcription factor CHOP (also called
      GADD153) is induced by ER stress. We report here that the transcription factor
      XBP-1 (also called TREB5) is also induced by ER stress and that induction of CHOP
      and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N(9)-CCACG.
      As the general transcription factor NF-Y (also known as CBF) binds to CCAAT,
      CCACG is considered to provide specificity in the mammalian UPR. We recently
      found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding
      protein is synthesized as a transmembrane protein in the ER, and ER stress
      induced proteolysis produces a soluble form of ATF6 that translocates into the
      nucleus. We report here that overexpression of soluble ATF6 activates
      transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes
      constitutively, whereas overexpression of a dominant negative mutant of ATF6
      blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6
      binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound
      to NF-Y. Based on these and other findings, we concluded that specific and direct
      interactions between ATF6 and ERSE are critical for transcriptional induction not
      only of ER chaperones but also of CHOP and XBP-1.

PMID- 10958674
TI  - Myc is an essential negative regulator of platelet-derived growth factor beta
      receptor expression.
AB  - Platelet-derived growth factor BB (PDGF BB) is a potent mitogen for fibroblasts
      as well as many other cell types. Interaction of PDGF BB with the PDGF beta
      receptor (PDGF-betaR) activates numerous signaling pathways and leads to a
      decrease in receptor expression on the cell surface. PDGF-betaR downregulation is
      effected at two levels, the immediate internalization of ligand-receptor
      complexes and the reduction in pdgf-betar mRNA expression. Our studies show that
      pdgf-betar mRNA suppression is regulated by the c-myc proto-oncogene. Both
      constitutive and inducible ectopic Myc protein can suppress pdgf-betar mRNA and
      protein. Suppression of pdgf-betar mRNA in response to Myc is specific, since
      expression of the related receptor pdgf-alphar is not affected. We further show
      that Myc suppresses pdgf-betar mRNA expression by a mechanism which is
      distinguishable from Myc autosuppression. Analysis of c-Myc-null fibroblasts
      demonstrates that Myc is required for the repression of pdgf-betar mRNA
      expression in quiescent fibroblasts following mitogen stimulation. In addition,
      it is evident that the Myc-mediated repression of pdgf-betar mRNA levels plays an
      important role in the regulation of basal pdgf-betar expression in proliferating
      cells. Thus, our studies suggest an essential role for Myc in a negative-feedback
      loop regulating the expression of the PDGF-betaR.

PMID- 10958676
TI  - Role of the LXCXE binding site in Rb function.
AB  - Oncoproteins from DNA tumor viruses such as adenovirus E1a, simian virus 40 T
      antigen, and human papillomavirus E7 contain an LXCXE sequence, which they use to
      bind the retinoblastoma protein (Rb) and inhibit its function. Cellular proteins
      such as histone deacetylases 1 and 2 (HDAC1 and -2) also contain an LXCXE-like
      sequence, which they use to interact with Rb. The LXCXE binding site in Rb was
      mutated to assess its role in Rb function. These mutations inhibited binding to
      HDAC1 and -2, which each contain an LXCXE-like sequence, but had no effect on
      binding to HDAC3, which lacks an LXCXE-like sequence. Mutation of the LXCXE
      binding site inhibited active transcriptional repression by Rb and prevented it
      from effectively repressing the cyclin E and A gene promoters. In contrast,
      mutations in the LXCXE binding site did not prevent Rb from binding and
      inactivating E2F. Thus, the LXCXE mutations appear to separate Rb's ability to
      bind and inactivate E2F from its ability to efficiently recruit HDAC1 and -2 and
      actively repress transcription. In transient assays, several of the LXCXE binding
      site mutants caused an increase in the percentage of cells in G(1) by flow
      cytometry, suggesting that they can arrest cells. However, this effect was
      transient, as none of the mutants affected cell proliferation in longer-term
      assays examining bromodeoxyuridine incorporation or colony formation. Our results
      then suggest that the LXCXE binding site is important for full Rb function.
      Mutation of the LXCXE binding site does not inhibit binding of the BRG1 ATPase
      component of the SWI/SNF nucleosome remodeling complex, which has been shown
      previously to be important for Rb function. Indeed, overexpression of BRG1 and Rb
      in cells deficient for the proteins led to stable growth inhibition, suggesting a
      cooperative role for SWI/SNF and the LXCXE binding site in efficient Rb function.

PMID- 10958677
TI  - Characterization of the interaction between the nuclease and reverse
      transcriptase activity of the yeast telomerase complex.
AB  - Telomerase is a ribonucleoprotein that mediates extension of the dG-rich strand
      of telomeres in most eukaryotes. Like telomerase derived from ciliated protozoa,
      yeast telomerase is found to possess a tightly associated endonuclease activity
      that copurifies with the polymerization activity over different affinity
      chromatographic steps. As is the case for ciliate telomerase, primers containing
      sequences that are not complementary to the RNA template can be efficiently
      cleaved by the yeast enzyme. More interestingly, we found that for the yeast
      enzyme, cleavage site selection is not stringent, since blocking cleavage at one
      site by the introduction of a nonhydrolyzable linkage can lead to the utilization
      of other sites. In addition, the reverse transcriptase activity of yeast
      telomerase can extend either the 5'- or 3'-end fragment following cleavage. Two
      general models that are consistent with the biochemical properties of the enzyme
      are presented: one model postulates two distinct active sites for the nuclease
      and reverse transcriptase, and the other invokes a multimeric enzyme with each
      protomer containing a single active site capable of mediating both cleavage and
      extension.

PMID- 10958675
TI  - Both src-dependent and -independent mechanisms mediate phosphatidylinositol 3
      kinase regulation of colony-stimulating factor 1-activated mitogen-activated
      protein kinases in myeloid progenitors.
AB  - Colony-stimulating factor 1 (CSF-1) supports the proliferation, survival, and
      differentiation of bone marrow-derived cells of the monocytic lineage. In the
      myeloid progenitor 32D cell line expressing CSF-1 receptor (CSF-1R), CSF-1
      activation of the extracellular signal-regulated kinase (ERK) pathway is both Ras
      and phosphatidylinositol 3-kinase (PI3-kinase) dependent. PI3-kinase inhibition
      did not influence events leading to Ras activation. Using the activity of the PI3
      kinase effector, Akt, as readout, studies with dominant-negative and oncogenic
      Ras failed to place PI3-kinase downstream of Ras. Thus, PI3-kinase appears to act
      in parallel to Ras. PI3-kinase inhibitors enhanced CSF-1-stimulated A-Raf and c
      Raf-1 activities, and dominant-negative A-Raf but not dominant-negative c-Raf-1
      reduced CSF-1-provoked ERK activation, suggesting that A-Raf mediates a part of
      the stimulatory signal from Ras to MEK/ERK, acting in parallel to PI3-kinase.
      Unexpectedly, a CSF-1R lacking the PI3-kinase binding site (DeltaKI) remained
      capable of activating MEK/ERK in a PI3-kinase-dependent manner. To determine if
      Src family kinases (SFKs) are involved, we demonstrated that CSF-1 activated Fyn
      and Lyn in cells expressing wild-type (WT) or DeltaKI receptors. Moreover, CSF-1
      induced Akt activity in cells expressing DeltaKI is SFK dependent since Akt
      activation was prevented by pharmacological or genetic inhibition of SFK
      activity. The docking protein Gab2 may link SFK to PI3-kinase. CSF-1 induced Gab2
      tyrosyl phosphorylation and association with PI3-kinase in cells expressing WT or
      DeltaKI receptors. However, only in DeltaKI cells are these events prevented by
      PP1. Thus in myeloid progenitors, CSF-1 can activate the PI3-kinase/Akt pathway
      by at least two mechanisms, one involving direct receptor binding and one
      involving SFKs.

PMID- 10958678
TI  - Human genomic sequences that inhibit splicing.
AB  - Mammalian genes are characterized by relatively small exons surrounded by
      variable lengths of intronic sequence. Sequences similar to the splice signals
      that define the 5' and 3' boundaries of these exons are also present in abundance
      throughout the surrounding introns. What causes the real sites to be
      distinguished from the multitude of pseudosites in pre-mRNA is unclear. Much
      progress has been made in defining additional sequence elements that enhance the
      use of particular sites. Less work has been done on sequences that repress the
      use of particular splice sites. To find additional examples of sequences that
      inhibit splicing, we searched human genomic DNA libraries for sequences that
      would inhibit the inclusion of a constitutively spliced exon. Genetic selection
      experiments suggested that such sequences were common, and we subsequently tested
      randomly chosen restriction fragments of about 100 bp. When inserted into the
      central exon of a three-exon minigene, about one in three inhibited inclusion,
      revealing a high frequency of inhibitory elements in human DNA. In contrast, only
      1 in 27 Escherichia coli DNA fragments was inhibitory. Several previously
      identified silencing elements derived from alternatively spliced exons functioned
      weakly in this constitutively spliced exon. In contrast, a high-affinity site for
      U2AF65 strongly inhibited exon inclusion. Together, our results suggest that
      splicing occurs in a background of repression and, since many of our inhibitors
      contain splice like signals, we suggest that repression of some pseudosites may
      occur through an inhibitory arrangement of these sites.

PMID- 10958679
TI  - Hsp72-mediated suppression of c-Jun N-terminal kinase is implicated in
      development of tolerance to caspase-independent cell death.
AB  - Pretreatment with mild heat shock is known to protect cells from severe stress
      (acquired thermotolerance). Here we addressed the mechanism of this phenomenon by
      using primary human fibroblasts. Severe heat shock (45 degrees C, 75 min) of the
      fibroblasts caused cell death displaying morphological characteristics of
      apoptosis; however, it was caspase independent. This cell death process was
      accompanied by strong activation of Akt, extracellular signal-regulated kinase 1
      (ERK1) and ERK2, p38, and c-Jun N-terminal (JNK) kinases. Suppression of Akt or
      ERK1 and -2 kinases increased cell thermosensitivity. In contrast, suppression of
      stress kinase JNK rendered cells thermoresistant. Development of thermotolerance
      was not associated with Akt or ERK1 and -2 regulation, and inhibition of these
      kinases did not reduce acquired thermotolerance. On the other hand, acquired
      tolerance to severe heat shock was associated with downregulation of JNK. Using
      an antisense-RNA approach, we found that accumulation of the heat shock protein
      Hsp72 is necessary for JNK downregulation and is critical for thermotolerance.
      The capability of naive cells to withstand moderate heat treatment also appears
      to be dependent on the accumulation of Hsp72 induced by this stress. Indeed,
      exposure to 45 degrees C for 45 min caused only transient JNK activation and was
      nonlethal, while prevention of Hsp72 accumulation prolonged JNK activation and
      led to massive cell death. We also found that JNK activation by UV irradiation,
      interleukin-1, or tumor necrosis factor was suppressed in thermotolerant cells
      and that Hsp72 accumulation was responsible for this effect. Hsp72-mediated
      suppression of JNK is therefore critical for acquired thermotolerance and may
      play a role in tolerance to other stresses.

PMID- 10958680
TI  - G protein-coupled receptor-mediated mitogen-activated protein kinase activation
      through cooperation of Galpha(q) and Galpha(i) signals.
AB  - G protein-coupled receptors (GPCRs) have been shown to stimulate extracellular
      regulated kinases (ERKs) through a number of linear pathways that are initiated
      by G(q/11) or G(i) proteins. We studied signaling to the ERK cascade by receptors
      that simultaneously activate both G protein subfamilies. In HEK293T cells,
      bradykinin B(2) receptor (B(2)R)-induced stimulation of ERK2 and transcriptional
      activity of Elk1 are dependent on Galpha(q)-mediated protein kinase C (PKC) and
      on Galpha(i)-induced Ras activation, while they are independent of Gbetagamma
      subunits, phosphatidylinositol 3-kinase, and tyrosine kinases. Similar results
      were obtained with m(1) and m(3) muscarinic receptors in HEK293T cells and with
      the B(2)R in human and mouse fibroblasts, indicating a general mechanism in
      signaling toward the ERK cascade. Furthermore, the bradykinin-induced activation
      of ERK is strongly reduced in Galpha(q/11)-deficient fibroblasts. In addition, we
      found that constitutively active mutants of Galpha(q/11) or Galpha(i) proteins
      alone poorly stimulate ERK2, whereas a combination of both led to synergistic
      effects. We conclude that dually coupled GPCRs require a cooperation of Galpha(i)
      and G(q/11)-mediated pathways for efficient stimulation of the ERK cascade.
      Cooperative signaling by multiple G proteins thus might represent a novel concept
      implicated in the regulation of cellular responses by GPCRs.

PMID- 10958681
TI  - Cellular compartmentalization in insulin action: altered signaling by a lipid
      modified IRS-1.
AB  - While most receptor tyrosine kinases signal by recruiting SH2 proteins directly
      to phosphorylation sites on their plasma membrane receptor, the insulin receptor
      phosphorylates intermediary IRS proteins that are distributed between the
      cytoplasm and a state of loose association with intracellular membranes. To
      determine the importance of this distribution to IRS-1-mediated signaling, we
      constructed a prenylated, constitutively membrane-bound IRS-1 by adding the COOH
      terminal 9 amino acids from p21(ras), including the CAAX motif, to IRS-1 (IRS
      CAAX) and analyzed its function in 32D cells expressing the insulin receptor. IRS
      CAAX migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis than did IRS-1 and demonstrated increased levels of
      serine/threonine phosphorylation. Insulin-stimulated tyrosyl phosphorylation of
      IRS-CAAX was slightly decreased, while IRS-CAAX-mediated phosphatidylinositol 3'
      kinase (PI3'-kinase) binding and activation were decreased by approximately 75%
      compared to those for wild-type IRS-1. Similarly, expression of IRS-CAAX
      desensitized insulin-stimulated [(3)H]thymidine incorporation into DNA by about
      an order of magnitude compared to IRS-1. By contrast, IRS-CAAX-expressing cells
      demonstrated increased signaling by mitogen-activated protein kinase, Akt, and
      p70(S6) kinase in response to insulin. Hence, tight association with the membrane
      increased IRS-1 serine phosphorylation and reduced coupling between the insulin
      receptor, PI3'-kinase, and proliferative signaling while enhancing other
      signaling pathways. Thus, the correct distribution of IRS-1 between the cytoplasm
      and membrane compartments is critical to the normal balance in the network of
      insulin signaling.

PMID- 10958682
TI  - 5' phospholipid phosphatase SHIP-2 causes protein kinase B inactivation and cell
      cycle arrest in glioblastoma cells.
AB  - The tumor suppressor protein PTEN is mutated in glioblastoma multiform brain
      tumors, resulting in deregulated signaling through the phosphoinositide 3-kinase
      (PI3K)-protein kinase B (PKB) pathway, which is critical for maintaining
      proliferation and survival. We have examined the relative roles of the two major
      phospholipid products of PI3K activity, phosphatidylinositol 3,4-biphosphate
      [PtdIns(3,4)P2] and phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3], in
      the regulation of PKB activity in glioblastoma cells containing high levels of
      both of these lipids due to defective PTEN expression. Reexpression of PTEN or
      treatment with the PI3K inhibitor LY294002 abolished the levels of both PtdIns(3,
      4)P2 and PtdIns(3,4,5)P3, reduced phosphorylation of PKB on Thr308 and Ser473,
      and inhibited PKB activity. Overexpression of SHIP-2 abolished the levels of
      PtdIns(3,4,5)P3, whereas PtdIns(3,4)P2 levels remained high. However, PKB
      phosphorylation and activity were reduced to the same extent as they were with
      PTEN expression. PTEN and SHIP-2 also significantly decreased the amount of PKB
      associated with cell membranes. Reduction of SHIP-2 levels using antisense
      oligonucleotides increased PKB activity. SHIP-2 became tyrosine phosphorylated
      following stimulation by growth factors, but this did not significantly alter its
      phosphatase activity or ability to antagonize PKB activation. Finally we found
      that SHIP-2, like PTEN, caused a potent cell cycle arrest in G(1) in glioblastoma
      cells, which is associated with an increase in the stability of expression of the
      cell cycle inhibitor p27(KIP1). Our results suggest that SHIP-2 plays a negative
      role in regulating the PI3K-PKB pathway.

PMID- 10958683
TI  - FRL, a novel formin-related protein, binds to Rac and regulates cell motility and
      survival of macrophages.
AB  - We have isolated a cDNA, frl (formin-related gene in leukocytes), a novel
      mammalian member of the formin gene family. The frl cDNA encodes a 160-kDa
      protein, FRL, that possesses FH1, FH2, and FH3 domains that are well conserved
      among other Formin-related proteins. An FRL protein is mainly localized in the
      cytosol and is highly expressed in spleen, lymph node, and bone marrow cells.
      Formin-related genes and proteins have been reported to play crucial roles in
      morphogenesis, cell polarity, and cytokinesis through interaction with Rho family
      small GTPases. FRL binds to Rac at its N-terminal region including the FH3 domain
      and associates with profilin at the FH1 domain. In a macrophage cell line,
      P388D1, overexpression of a truncated form of FRL containing only the FH3 domain
      (FH3-FRL) strongly inhibited cell adhesion to fibronectin and migration upon
      stimulation with a chemokine. Moreover, expression of the truncated FH3-FRL
      protein resulted in apoptotic cell death of P388D1 cells, suggesting that the
      truncated FH3-FRL protein may interfere with signals of FRL. Overexpression in
      the P388D1 cells of full-length FRL or of the truncated protein containing the
      FH3 and FH1 domains, with simultaneous expression of the truncated FH3-FRL
      protein, blocked apoptotic cell death and inhibition of cell adhesion and
      migration. These results suggest that FRL may play a role in the control of
      reorganization of the actin cytoskeleton in association with Rac and also in the
      regulation of the signal for cell survival.

PMID- 10958684
TI  - Beta-catenin-histone deacetylase interactions regulate the transition of LEF1
      from a transcriptional repressor to an activator.
AB  - Recent evidence suggests that certain LEF/TCF family members act as repressors in
      the absence of Wnt signaling. We show here that repression by LEF1 requires
      histone deacetylase (HDAC) activity. Further, LEF1 associates in vivo with HDAC1,
      and transcription of a model LEF1-dependent target gene is modulated by the ratio
      of HDAC1 to beta-catenin, implying that repression by LEF1 is mediated by
      promoter-targeted HDAC. Consistent with this hypothesis, under repression
      conditions the promoter region of a LEF1 target gene is hypoacetylated. By
      contrast, when the reporter is activated, its promoter becomes hyperacetylated.
      Coexpression of beta-catenin with LEF1 and HDAC1 results in the formation of a
      beta-catenin/HDAC1 complex. Surprisingly, the enzymatic activity of HDAC1
      associated with beta-catenin is attenuated. Together, these findings imply that
      activation of LEF1-dependent genes by beta-catenin involves a two-step mechanism.
      First, HDAC1 is dissociated from LEF1 and its enzymatic activity is attenuated.
      This first step yields a promoter that is inactive but poised for activation.
      Second, once HDAC1-dependent repression has been overridden, beta-catenin binds
      LEF1 and the beta-catenin-LEF1 complex is competent to activate the expression of
      downstream target genes.

PMID- 10958685
TI  - Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin
      1beta-induced histone H4 acetylation on lysines 8 and 12.
AB  - We have investigated the ability of dexamethasone to regulate interleukin-1beta
      (IL-1beta)-induced gene expression, histone acetyltransferase (HAT) and histone
      deacetylase (HDAC) activity. Low concentrations of dexamethasone (10(-10) M)
      repress IL-1beta-stimulated granulocyte-macrophage colony-stimulating factor (GM
      CSF) expression and fail to stimulate secretory leukocyte proteinase inhibitor
      expression. Dexamethasone (10(-7) M) and IL-1beta (1 ng/ml) both stimulated HAT
      activity but showed a different pattern of histone H4 acetylation. Dexamethasone
      targeted lysines K5 and K16, whereas IL-1beta targeted K8 and K12. Low
      concentrations of dexamethasone (10(-10) M), which do not transactivate,
      repressed IL-1beta-stimulated K8 and K12 acetylation. Using chromatin
      immunoprecipitation assays, we show that dexamethasone inhibits IL-1beta-enhanced
      acetylated K8-associated GM-CSF promoter enrichment in a concentration-dependent
      manner. Neither IL-1beta nor dexamethasone elicited any GM-CSF promoter
      association at acetylated K5 residues. Furthermore, we show that GR acts both as
      a direct inhibitor of CREB binding protein (CBP)-associated HAT activity and also
      by recruiting HDAC2 to the p65-CBP HAT complex. This action does not involve de
      novo synthesis of HDAC protein or altered expression of CBP or p300/CBP
      associated factor. This mechanism for glucocorticoid repression is novel and
      establishes that inhibition of histone acetylation is an additional level of
      control of inflammatory gene expression. This further suggests that
      pharmacological manipulation of of specific histone acetylation status is a
      potentially useful approach for the treatment of inflammatory diseases.

PMID- 10958686
TI  - Regulation of histone deacetylase 4 by binding of 14-3-3 proteins.
AB  - Histone (de)acetylation is important for the regulation of fundamental biological
      processes such as gene expression and DNA recombination. Distinct classes of
      histone deacetylases (HDACs) have been identified, but how they are regulated in
      vivo remains largely unexplored. Here we describe results demonstrating that
      HDAC4, a member of class II human HDACs, is localized in the cytoplasm and/or the
      nucleus. Moreover, we have found that HDAC4 interacts with the 14-3-3 family of
      proteins that are known to bind specifically to conserved phosphoserine
      containing motifs. Deletion analyses suggested that S246, S467, and S632 of HDAC4
      mediate this interaction. Consistent with this, alanine substitutions of these
      serine residues abrogated 14-3-3 binding. Although these substitutions had
      minimal effects on the deacetylase activity of HDAC4, they stimulated its nuclear
      localization and thus led to enhanced transcriptional repression. These results
      indicate that 14-3-3 proteins negatively regulate HDAC4 by preventing its nuclear
      localization and thereby uncover a novel regulatory mechanism for HDACs.

PMID- 10958688
TI  - Sls1p stimulates Sec63p-mediated activation of Kar2p in a conformation-dependent
      manner in the yeast endoplasmic reticulum.
AB  - We previously characterized the SLS1 gene in the yeast Yarrowia lipolytica and
      showed that it interacts physically with YlKar2p to promote translocation across
      the endoplasmic-reticulum membrane (A. Boisrame, M. Kabani, J. M. Beckerich, E.
      Hartmann, and C. Gaillardin, J. Biol. Chem. 273:30903-30908, 1998). A Y.
      lipolytica Kar2p mutant was isolated that restored interaction with an Sls1p
      mutant, suggesting that the interaction with Sls1p could be nucleotide and/or
      conformation dependent. This result was used as a working hypothesis for more
      accurate investigations in Saccharomyces cerevisiae. We show by two-hybrid an in
      vitro assays that the S. cerevisiae homologue of Sls1p interacts with ScKar2p.
      Using dominant lethal mutants of ScKar2p, we were able to show that ScSls1p
      preferentially interacts with the ADP-bound conformation of the molecular
      chaperone. Synthetic lethality was observed between DeltaScsls1 and translocation
      deficient kar2 or sec63-1 mutants, providing in vivo evidence for a role of
      ScSls1p in protein translocation. Synthetic lethality was also observed with ER
      associated degradation and folding-deficient kar2 mutants, strongly suggesting
      that Sls1p functions are not restricted to the translocation process. We show
      that Sls1p stimulates in a dose-dependent manner the binding of ScKar2p on the
      lumenal J domain of Sec63p fused to glutathione S-transferase. Moreover, Sls1p is
      shown to promote the Sec63p-mediated activation of Kar2p's ATPase activity. Our
      data strongly suggest that Sls1p could be the first GrpE-like protein described
      in the endoplasmic reticulum.

PMID- 10958687
TI  - Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage,
      nuclear translocation, and hyperphosphorylation of Notch2.
AB  - Delta1, Jagged1, and Jagged2, commonly designated Delta/Serrate/LAG-2 (DSL)
      proteins, are known to be ligands for Notch1. However, it has been less
      understood whether they are ligands for Notch receptors other than Notch1.
      Meanwhile, ligand-induced cleavage and nuclear translocation of the Notch protein
      are considered to be fundamental for Notch signaling, yet direct observation of
      the behavior of the Notch molecule after ligand binding, including cleavage and
      nuclear translocation, has been lacking. In this report, we investigated these
      issues for Notch2. All of the three DSL proteins bound to endogenous Notch2 on
      the surface of BaF3 cells, although characteristics of Jagged2 for binding to
      Notch2 apparently differed from that of Delta1 and Jagged1. After binding, the
      three DSL proteins induced cleavage of the membrane-spanning subunit of Notch2
      (Notch2(TM)), which occurred within 15 min. In a simultaneous time course, the
      cleaved fragment of Notch2(TM) was translocated into the nucleus. Interestingly,
      the cleaved Notch2 fragment was hyperphosphorylated also in a time-dependent
      manner. Finally, binding of DSL proteins to Notch2 also activated the
      transcription of reporter genes driven by the RBP-Jkappa-responsive promoter.
      Together, these data indicate that all of these DSL proteins function as ligands
      for Notch2. Moreover, the findings of rapid cleavage, nuclear translocation, and
      phosphorylation of Notch2 after ligand binding facilitate the understanding of
      the Notch signaling.

PMID- 10958689
TI  - takeout, a novel Drosophila gene under circadian clock transcriptional
      regulation.
AB  - We report the identification and characterization of a new Drosophila clock
      regulated gene, takeout (to). to is a member of a novel gene family and is
      implicated in circadian control of feeding behavior. Its gene expression is down
      regulated in all of the clock mutants tested. In wild-type flies, to mRNA
      exhibits daily cycling expression but with a novel phase, delayed relative to
      those of the better-characterized clock mRNAs, period and timeless. The E-box
      containing sequence in the to promoter shows impressive similarities with those
      of period and timeless. However, our results suggest that the E box is not
      involved in the amplitude and phase of the transcriptional cycling of to. The
      circadian delayed transcriptional phase is therefore most likely the result of
      indirect regulation through unknown transcription factors.

PMID- 10958690
TI  - Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to
      the plasma membrane and hyperresponsiveness to CD3 stimulation.
AB  - Pleckstrin homology (PH) domain binding to D3-phosphorylated
      phosphatidylinositides (PI) provides a reversible means of recruiting proteins to
      the plasma membrane, with the resultant change in subcellular localization
      playing a key role in the activation of multiple intracellular signaling
      pathways. Previously we found that the T-cell-specific PH domain-containing
      kinase Itk is constitutively membrane associated in Jurkat T cells. This
      distribution was unexpected given that the closely related B-cell kinase, Btk, is
      almost exclusively cytosolic. In addition to constitutive membrane association of
      Itk, unstimulated JTAg T cells also exhibited constitutive phosphorylation of Akt
      on Ser-473, an indication of elevated basal levels of the phosphatidylinositol 3
      kinase (PI3K) products PI-3,4-P(2) and PI-3,4,5-P(3) in the plasma membrane. Here
      we describe a defect in expression of the D3 phosphoinositide phosphatase, PTEN,
      in Jurkat and JTAg T cells that leads to unregulated PH domain interactions with
      the plasma membrane. Inhibition of D3 phosphorylation by PI3K inhibitors, or by
      expression of PTEN, blocked constitutive phosphorylation of Akt on Ser-473 and
      caused Itk to redistribute to the cytosol. The PTEN-deficient cells were also
      hyperresponsive to T-cell receptor (TCR) stimulation, as measured by Itk kinase
      activity, tyrosine phosphorylation of phospholipase C-gamma1, and activation of
      Erk compared to those in PTEN-replete cells. These data support the idea that PH
      domain-mediated association with the plasma membrane is required for Itk
      activation, provide evidence for a negative regulatory role of PTEN in TCR
      stimulation, and suggest that signaling models based on results from Jurkat T
      cell lines may underestimate the role of PI3K in TCR signaling.

PMID- 10958691
TI  - CDK9 autophosphorylation regulates high-affinity binding of the human
      immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.
AB  - Human immunodeficiency virus type 1 (HIV-1) Tat interacts with cyclin T1 (CycT1),
      a regulatory partner of CDK9 in the positive transcription elongation factor (P
      TEFb) complex, and binds cooperatively with CycT1 to TAR RNA to recruit P-TEFb
      and promote transcription elongation. We show here that Tat also stimulates
      phosphorylation of affinity-purified core RNA polymerase II and glutathione S
      transferase-C-terminal-domain substrates by CycT1-CDK9, but not CycH-CDK7, in
      vitro. Interestingly, incubation of recombinant Tat-P-TEFb complexes with ATP
      enhanced binding to TAR RNA dramatically, and the C-terminal half of CycT1 masked
      binding of Tat to TAR RNA in the absence of ATP. ATP incubation lead to
      autophosphorylation of CDK9 at multiple C-terminal Ser and Thr residues, and full
      length CycT1 (amino acids 728) [CycT1(1-728)], but not truncated CycT1(1-303),
      was also phosphorylated by CDK9. P-TEFb complexes containing a catalytically
      inactive CDK9 mutant (D167N) bound TAR RNA weakly and independently of ATP, as
      did a C-terminal truncated CDK9 mutant that was catalytically active but unable
      to undergo autophosphorylation. Analysis of different Tat proteins revealed that
      the 101-amino-acid SF2 HIV-1 Tat was unable to bind TAR with CycT1(1-303) in the
      absence of phosphorylated CDK9, whereas unphosphorylated CDK9 strongly blocked
      binding of HIV-2 Tat to TAR RNA in a manner that was reversed upon
      autophosphorylation. Replacement of CDK9 phosphorylation sites with negatively
      charged residues restored binding of CycT1(1-303)-D167N-Tat, and rendered D167N a
      more potent inhibitor of transcription in vitro. Taken together, these results
      demonstrate that CDK9 phosphorylation is required for high-affinity binding of
      Tat-P-TEFb to TAR RNA and that the state of P-TEFb phosphorylation may regulate
      Tat transactivation in vivo.

PMID- 10958692
TI  - Conservation of heterochromatin protein 1 function.
AB  - Heterochromatin represents a cytologically visible state of heritable gene
      repression. In the yeast, Schizosaccharomyces pombe, the swi6 gene encodes a
      heterochromatin protein 1 (HP1)-like chromodomain protein that localizes to
      heterochromatin domains, including the centromeres, telomeres, and the donor
      mating-type loci, and is involved in silencing at these loci. We identify here
      the functional domains of swi6p and demonstrate that the chromodomain from a
      mammalian HP1-like protein, M31, can functionally replace that of swi6p, showing
      that chromodomain function is conserved from yeasts to humans. Site-directed
      mutagenesis, based on a modeled three-dimensional structure of the swi6p
      chromodomain, shows that the hydrophobic amino acids which lie in the core of the
      structure are critical for biological function. Gel filtration, gel overlay
      experiments, and mass spectroscopy show that HP1 proteins can self-associate, and
      we suggest that it is as oligomers that HP1 proteins are incorporated into
      heterochromatin complexes that silence gene activity.

PMID- 10958693
TI  - p50(Cdc37) can buffer the temperature-sensitive properties of a mutant of Hck.
AB  - Genetic studies have previously revealed that Cdc37p is required for the
      catalytic competence of v-Src in yeast. We have reasoned that temperature
      sensitive mutants of Src family kinases might be more sensitive to the cellular
      level of p50(Cdc37), the mammalian homolog of Cdc37p, than their wild-type
      counterpart, thus potentially providing a unique opportunity to elucidate the
      involvement of p50(Cdc37) in the folding and stabilization of Src family kinases.
      A temperature-sensitive mutant of a constitutively active form of Hck (i.e.,
      tsHck499F) was created by mutating two amino acids within the kinase domain of
      Hck499F. Significantly, overexpression of p50(Cdc37) rescues the catalytic
      activity of tsHck499F at 33 degrees C, while partially buffering it against
      inactivation at higher temperatures (e.g., 37 and 39 degrees C). Hsp90 function
      is required for tsHck499F activity and its stabilization by p50(Cdc37), but
      overexpression of Hsp90 is not sufficient to stabilize tsHck499F. Overexpression
      of p50(Cdc37) promotes the association of tsHck499F with Hsp90, suggesting that
      the cellular level of p50(Cdc37) might be the rate-limiting step in the
      association of tsHck499F with Hsp90. A truncation mutant of p50(Cdc37) that
      cannot bind Hsp90 still has a limited capacity to rescue the catalytic activity
      of tsHck499F and promote its association with Hsp90. This is a particularly
      important observation, since it argues that rather than solely acting as a
      passive adapter protein to tether tsHck499F to Hsp90, p50(Cdc37) may also act
      allosterically to enhance the association of tsHck499F with Hsp90. The findings
      presented here might also have implications for our understanding of the
      evolution of protein kinases and tumor development.

PMID- 10958694
TI  - A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of
      Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early
      stage of mitotic chromosome condensation.
AB  - Structural maintenance of chromosomes (SMC) family proteins play critical roles
      in structural changes of chromosomes. Previously, we identified two human SMC
      family proteins, hCAP-C and hCAP-E, which form a heterodimeric complex (hCAP-C
      hCAP-E) in the cell. Based on the sequence conservation and mitotic chromosome
      localization, hCAP-C-hCAP-E was determined to be the human ortholog of the
      Xenopus SMC complex, XCAP-C-XCAP-E. XCAP-C-XCAP-E is a component of the
      multiprotein complex termed condensin, required for mitotic chromosome
      condensation in vitro. However, presence of such a complex has not been
      demonstrated in mammalian cells. Coimmunoprecipitation of the endogenous hCAP-C
      hCAP-E complex from HeLa extracts identified a 155-kDa protein interacting with
      hCAP-C-hCAP-E, termed condensation-related SMC-associated protein 1 (CNAP1).
      CNAP1 associates with mitotic chromosomes and is homologous to Xenopus condensin
      component XCAP-D2, indicating the presence of a condensin complex in human cells.
      Chromosome association of human condensin is mitosis specific, and the majority
      of condensin dissociates from chromosomes and is sequestered in the cytoplasm
      throughout interphase. However, a subpopulation of the complex was found to
      remain on chromosomes as foci in the interphase nucleus. During late G(2)/early
      prophase, the larger nuclear condensin foci colocalize with phosphorylated
      histone H3 clusters on partially condensed regions of chromosomes. These results
      suggest that mitosis-specific function of human condensin may be regulated by
      cell cycle-specific subcellular localization of the complex, and the nuclear
      condensin that associates with interphase chromosomes is involved in the
      reinitiation of mitotic chromosome condensation in conjunction with
      phosphorylation of histone H3.

PMID- 10958695
TI  - The absence of nidogen 1 does not affect murine basement membrane formation.
AB  - Nidogen 1 is a highly conserved protein in mammals, Drosophila melanogaster,
      Caenorhabditis elegans, and ascidians and is found in all basement membranes. It
      has been proposed that nidogen 1 connects the laminin and collagen IV networks,
      so stabilizing the basement membrane, and integrates other proteins, including
      perlecan, into the basement membrane. To define the role of nidogen 1 in basement
      membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic
      stem cells and used these to derive mouse lines. Homozygous animals produce
      neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt
      abnormalities and are fertile, their basement membrane structures appearing
      normal. Nidogen 2 staining is increased in certain basement membranes, where it
      is normally only found in scant amounts. This occurs by either redistribution
      from other extracellular matrices or unmasking of nidogen 2 epitopes, as its
      production does not appear to be upregulated. The results show that nidogen 1 is
      not required for basement membrane formation or maintenance.

PMID- 10958696
TI  - Identifying a core RNA polymerase surface critical for interactions with a sigma
      like specificity factor.
AB  - Cyclic interactions occurring between a core RNA polymerase (RNAP) and its
      initiation factors are critical for transcription initiation, but little is known
      about subunit interaction. In this work we have identified regions of the single
      subunit yeast mitochondrial RNAP (Rpo41p) important for interaction with its
      sigma-like specificity factor (Mtf1p). Previously we found that the whole folded
      structure of both polypeptides as well as specific amino acids in at least three
      regions of Mtf1p are required for interaction. In this work we started with an
      interaction-defective point mutant in Mtf1p (V135A) and used a two-hybrid
      selection to isolate suppressing mutations in the core polymerase. We identified
      suppressors in three separate regions of the RNAP which, when modeled on the
      structure of the closely related phage T7 RNAP, appear to lie on one surface of
      the protein. Additional point mutations and biochemical assays were used to
      confirm the importance of each region for Rpo41p-Mtf1p interactions. Remarkably,
      two of the three suppressors are found in regions required by T7 RNAP for DNA
      sequence recognition and promoter melting. Although these essential regions of
      the phage RNAP are poorly conserved with the mitochondrial RNAPs, they are
      conserved among the mitochondrial enzymes. The organellar RNAPs appear to use
      this surface in an alternative way for interactions with their separate sigma
      like specificity factor, which, like its bacterial counterpart, provides promoter
      recognition and DNA melting functions to the holoenzyme.

PMID- 10958699
TI  - Molecular characterization of the murine orthologue of the human retinal
      proteoglycan IPM 150.
AB  - PURPOSE: We recently identified a family of novel human
      proteoglycans/glycoproteins that are major constituents of the human
      interphotoreceptor matrix. Two members of this family, designated IPM 150 and IPM
      200, have been extensively characterized. Although the IPM is thought to mediate
      crucial roles in retinal physiology, including retinal adhesion and photoreceptor
      cell viability, little is known about the roles of specific IPM constituents in
      these processes. In order to characterize the mouse IPM 150 orthologue, to
      initiate functional in vivo studies, and as a prerequisite towards future genetic
      manipulation, we cloned the murine orthologue of human IPM 150 and determined its
      chromosomal location. METHODS: A mouse retinal cDNA library was screened using an
      IMAGE clone with sequence similarity to human IPM 150. The genomic location of
      the mouse IPM 150 gene was determined by radiation hybrid analyses. RESULTS: We
      describe here the molecular structure of the murine orthologue of human IPM 150
      and place the location of its gene on mouse chromosome 9. Among the tissues
      examined, expression of IPM 150 appeared to be restricted to the retina.
      CONCLUSIONS: Comparison of the human and murine IPM 150 core proteins revealed
      that the molecules are generally well conserved, although several potentially
      significant differences do exist. In addition, two highly conserved domains
      within the core proteins were identified. The data presented here represent a
      first step towards the development of experimental murine models, which may
      eventually be used to elucidate the mechanisms underlying retinal adhesion and
      photoreceptor survival.

PMID- 10958700
TI  - Q&A about this issue

PMID- 10958698
TI  - The N terminus of the centromere H3-like protein Cse4p performs an essential
      function distinct from that of the histone fold domain.
AB  - Cse4p is an evolutionarily conserved histone H3-like protein that is thought to
      replace H3 in a specialized nucleosome at the yeast (Saccharomyces cerevisiae)
      centromere. All known yeast, worm, fly, and human centromere H3-like proteins
      have highly conserved C-terminal histone fold domains (HFD) but very different N
      termini. We have carried out a comprehensive and systematic mutagenesis of the
      Cse4p N terminus to analyze its function. Surprisingly, only a 33-amino-acid
      domain within the 130-amino-acid-long N terminus is required for Cse4p N-terminal
      function. The spacing of the essential N-terminal domain (END) relative to the
      HFD can be changed significantly without an apparent effect on Cse4p function.
      The END appears to be important for interactions between Cse4p and known
      kinetochore components, including the Ctf19p/Mcm21p/Okp1p complex. Genetic and
      biochemical evidence shows that Cse4p proteins interact with each other in vivo
      and that nonfunctional cse4 END and HFD mutant proteins can form functional mixed
      complexes. These results support different roles for the Cse4p N terminus and the
      HFD in centromere function and are consistent with the proposed Cse4p nucleosome
      model. The structure-function characteristics of the Cse4p N terminus are
      relevant to understanding how other H3-like proteins, such as the human homolog
      CENP-A, function in kinetochore assembly and chromosome segregation.

PMID- 10958701
TI  - Surviving the tsunami of drug therapy expenditures.

PMID- 10958697
TI  - MyoD-dependent induction during myoblast differentiation of p204, a protein also
      inducible by interferon.
AB  - p204, an interferon-inducible p200 family protein, inhibits rRNA synthesis in
      fibroblasts by blocking the binding of the upstream binding factor transcription
      factor to DNA. Here we report that among 10 adult mouse tissues tested, the level
      of p204 was highest in heart and skeletal muscles. In cultured C2C12 skeletal
      muscle myoblasts, p204 was nucleoplasmic and its level was low. During myoblast
      fusion this level strongly increased, p204 became phosphorylated, and the bulk of
      p204 appeared in the cytoplasm of the myotubes. Leptomycin B, an inhibitor of
      nuclear export that blocked myoblast fusion, inhibited the nuclear export signal
      dependent translocation of p204 to the cytoplasm. The increase in the p204 level
      during myoblast fusion was a consequence of MyoD transcription factor binding to
      several MyoD-specific sequences in the gene encoding p204, followed by
      transcription. Overexpression of p204 (in C2C12 myoblasts carrying an inducible
      p204 expression plasmid) accelerated the fusion of myoblasts to myotubes in
      differentiation medium and induced the fusion even in growth medium. The level of
      p204 in mouse heart muscle strongly increased during differentiation; it was
      barely detectable in 10. 5-day-old embryos, reached the peak level in 16.5-day
      old embryos, and remained high thereafter. p204 is the second p200 family protein
      (after p202a) found to be involved in muscle differentiation. (p202a was formerly
      designated p202. The new designation is due to the identification of a highly
      similar protein-p202b [H. Wang, G. Chatterjee, J. J. Meyer, C. J. Liu, N. A.
      Manjunath, P. Bray-Ward, and P. Lengyel, Genomics 60:281-294, 1999].) These
      results reveal that p204 and p202a function in both muscle differentiation and
      interferon action.

PMID- 10958702
TI  - A complex conspiracy against the elderly: inappropriate prescribing.

PMID- 10958703
TI  - The cost of drug treatment in Ontario.

PMID- 10958704
TI  - Use of SSRIs in the elderly: obvious benefits but unappreciated risks.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are frequently recommended as a
      first-line treatment for depression in elderly patients. The evidence for this
      recommendation appears to be weak because studies that have examined the
      comparative efficacy, safety, tolerability and effectiveness of SSRIs and
      tricyclic antidepressants (TCAs) suggest that there are few advantages for one
      over another. Furthermore, a number of potential adverse effects of SSRIs are
      unappreciated risks. These include falls, hyponatremia, weight loss, sexual
      dysfunction and drug interactions. These potential risks, however, appear to be
      equally balanced by advantages such as fewer anticholinergic effects, a benign
      cardiovascular profile, ease of use and safety in overdose. SSRIs and TCAs have
      relative risks and benefits, and clinicians must maintain expertise in
      prescribing for elderly patients given both the frequency and severity of
      depressive disorders in late life.

PMID- 10958705
TI  - New drug approval times and 'therapeutic potential' in Canada, Australia, Sweden
      and the United States during the period 1992 to 1998.
AB  - In two previous studies, the times required to approve new drugs in Canada,
      Australia, Sweden, the United Kingdom and the United States during the periods
      1992 to 1995 and 1996 to 1998 were compared. However, during each of these two
      periods, only a fraction of the drugs that were approved in any of the countries
      were approved in all of them. Because an analysis based solely on drugs approved
      in all the countries would provide additional information, data from the previous
      studies have been used to compare drugs approved in each of Canada, Australia,
      Sweden and the United States during the period 1992 to 1998. In addition,
      applications that received a 'priority' or a 'standard' review by the United
      States Food and Drug Administration were analyzed separately to determine whether
      differences between the countries diminished for drugs considered to be of
      potentially greater therapeutic value. For the 87 drugs identified as being
      approved for marketing in all four countries during the period 1992 to 1998,
      approval times in Canada and Australia were not significantly different, but both
      Canada and Australia had significantly longer times than those of the United
      States and Sweden (P<0.001). Of the 87 drugs, 37 (43%) received a priority review
      in the United States. In both the priority and standard review categories, the
      Australian and Canadian median approval times were significantly longer than
      those in Sweden and the United States. The results demonstrate that, in general,
      both priority and standard new drug applications are reviewed more expeditiously
      in Sweden and the United States than in Canada. Canadian patients continue to
      experience delayed access to potentially valuable medicines.

PMID- 10958706
TI  - Development and validation of an improving prescribing in the elderly tool.
AB  - OBJECTIVE: To apply recently published consensus panel guidelines to a series of
      hospital inpatient charts to develop and validate a brief screening tool for
      potentially inappropriate prescriptions in the elderly. SETTING: A 400-bed acute
      care hospital in London, Ontario. METHODS: Three hundred and sixty-one
      consecutive inpatient charts, 185 from a clinical teaching unit (CTU) and 176
      from a geriatric assessment unit (GAU) were examined for potentially
      inappropriate prescriptions as listed by McLeod et al. The potentially
      inappropriate prescribing practices detected were used to develop the Improving
      Prescribing in the Elderly Tool (IPET). Construct validity was examined by
      looking for a predicted difference in the rate of potentially inappropriate
      prescriptions between the CTU and the GAU. Interrater reliability was determined
      by applying the IPET to a new series of 100 charts. RESULTS: Forty-two of 361
      individuals (12.5%) had 45 potentially inappropriate prescriptions representing
      14 different potential drug/disease interactions; these were used to construct
      the IPET. A demonstrated difference in the rate of potentially inappropriate
      prescriptions between the CTU and GAU indicated construct validity. The
      interrater reliability of the IPET (kappa) when applied to a new series of 100
      charts was 1.0. INTERPRETATION: The IPET is a brief, reliable and valid tool
      based on the published literature that may be used to screen for potentially
      inappropriate prescriptions in the elderly.

PMID- 10958707
TI  - Influence of the British Columbia reference drug program on hospital formularies:
      a survey of hospital pharmacy managers.
AB  - OBJECTIVES: To assess the impact of the British Columbia Reference Drug (RD)
      Program on the management of hospital formularies in the province. MATERIALS AND
      METHODS: A survey of pharmacy managers in British Columbia hospitals with more
      than 100 beds was conducted in November, 1997. The survey instrument contained
      questions regarding hospital characteristics, drugs listed on the formulary
      before and after implementation of RD policies for four drug classes, the
      hospitals' responses to RD policies and the respondents' opinions of the RD
      Program. RESULTS: Thirty-two (86%) hospitals returned the survey by the stated
      deadline. Before the RD Program was implemented, significantly more hospitals
      listed cimetidine (P=0.03), felodipine (P<0.001), quinapril (P<0.001) and
      ramipril (P<0.001) on the hospital drug formulary. The main reasons given for
      changes to hospital drug formularies were community prescribing patterns (25% to
      38%) and the RD Program (23% to 44%) depending on the drug category. Twenty-seven
      (84%) hospitals did not automatically adopt RD policies; 22 (69%) hospitals
      reviewed the policies at Pharmacy and Therapeutics Committee meetings. Sixteen
      (50%) respondents thought that hospitals should change their drug formularies to
      match the policies. Median satisfaction with the RD Program on a 10-point rating
      scale (1 = unsatisfied, 10 = satisfied) was 7 (range 2 to 10). CONCLUSIONS:
      Respondents appeared to be neutral when asked their opinion of the RD initiative.
      The RD policies resulted in drug category-dependent changes in the hospital
      formulary listings. H2 receptor antagonists and antihypertensives were the most
      significantly influenced drug categories. RD status does not automatically confer
      formulary status of a drug; however, it does appear to be a criterion in most
      hospitals when considering a drug for inclusion in the formulary.

PMID- 10958708
TI  - An evidence-based review of ACE inhibitors in incipient diabetic nephropathy.
AB  - Diabetic nephropathy develops in approximately 35% of diabetics and is the
      leading cause of end-stage renal disease in North America. End-stage renal
      disease is associated with increased morbidity and mortality, and a large
      economic burden. Treatments that can prevent or postpone diabetic nephropathy are
      important therapeutic advances. Interventional studies in type I diabetes and
      type II diabetes have demonstrated a beneficial effect of improved glycemic
      control and good blood pressure control in delaying the progression of diabetic
      nephropathy. Angiotensin-converting enzyme (ACE) inhibitors have been found to be
      effective in delaying the progression of diabetic nephropathy in hypertensive as
      well as normotensive diabetics with early and advanced nephropathy.
      Microalbuminuria or incipient diabetic nephropathy is the earliest clinical
      expression of diabetic nephropathy and identifies patients at risk of further
      progression. Advanced or overt nephropathy is associated with a greater risk for
      coronary artery disease and mortality. It is possible that interventions aimed
      earlier in the cascade at preventing the development of overt nephropathy may
      result in greater clinical benefit. There is compelling evidence of the benefit
      of ACE inhibitors in preventing the progression of incipient diabetic nephropathy
      to overt diabetic nephropathy in normotensive diabetics.

PMID- 10958709
TI  - Long-term followup of the hematuria-dysuria syndrome.
AB  - PURPOSE: The hematuria-dysuria syndrome is the most common reported complication
      of gastrocystoplasty. We reviewed our cases of gastrocystoplasty to determine the
      long-term incidence and significance of the syndrome. MATERIALS AND METHODS: We
      performed a retrospective study of 78 patients who underwent gastrocystoplasty at
      our institution between July 1989 and October 1994. A total of 72 of the 78 cases
      were evaluated within the last year to elicit symptoms of the hematuria-dysuria
      syndrome. RESULTS: Spina bifida and bladder exstrophy were the most common
      diagnoses of patients undergoing gastrocystoplasty. There were 3 (4%) patients
      who required medications on a continuous basis to control symptoms of the
      hematuria-dysuria syndrome. However, using broad criteria 17 (24%) patients would
      be categorized as having the syndrome. Of these patients 9 did not require any
      medications and 4 occasionally took medications to control symptoms. A
      significant increase in the incidence of the hematuria-dysuria syndrome was
      detected in those cases with a sensate compared to those with an insensate
      urethra. CONCLUSIONS: The hematuria-dysuria syndrome is a clinically significant
      problem at long-term followup in a small percentage of patients treated with
      gastrocystoplasty. The lowest incidence is in those children with an insensate
      urethra who are continent. When symptoms occur they are easily treated in the
      majority of cases. We believe that gastrocystoplasty remains a viable option in
      the armamentarium of bladder augmentation.

PMID- 10958710
TI  - Augmentation ureterocystoplasty could be performed more frequently.
AB  - PURPOSE: Megaureter represents the ideal tissue for bladder augmentation but to
      date ureterocystoplasty has been used only in select cases. We demonstrate that
      ureterocystoplasty can be used more frequently by dividing the megaureter and
      using its distal part for bladder augmentation and proximal part for
      reimplantation into the bladder. This technique can be performed as a 1 or 2
      stage procedure. MATERIALS AND METHODS: From November 1995 to October 1998
      ureterocystoplasty was performed in 16 patients 3 to 12 years old (mean age 6.6).
      In 9 cases with impaired renal function loop cutaneous ureterostomy had been
      previously done to preserve and improve renal function. In the remaining 7 cases
      bladder augmentation and simultaneous ureteroneocystostomy were performed without
      cutaneous ureterostomy. Ureterocystoplasty was done extraperitoneally. This
      distal part of megaureter was used for bladder augmentation and the proximal part
      was implanted into the bladder using extravesical detrusor tunneling
      ureteroneocystostomy in a majority of cases. RESULTS: Followup ranged from 12
      months to 4 years (mean 2.8). The new increased bladder capacity ranged 296 to
      442 ml. (mean 371) in both groups. Compliance was improved in all cases with a
      decrease in the number of clean intermittent catheterizations daily, and there
      was no further worsening of renal function. Vesicoureteral reflux was noted in 3
      patients without clinical symptoms. CONCLUSIONS: Megaureter presents the ideal
      tissue for bladder augmentation. Division of the ureter and use of its distal
      part for augmentation is always possible. Augmentation ureterocystoplasty
      performed this way can be done more frequently.

PMID- 10958711
TI  - Coculture of bladder urothelial and smooth muscle cells on small intestinal
      submucosa: potential applications for tissue engineering technology.
AB  - PURPOSE: Small intestinal submucosa is a xenogenic, acellular, collagen rich
      membrane with inherent growth factors that has previously been shown to promote
      in vivo bladder regeneration. We evaluate in vitro use of small intestinal
      submucosa to support the individual and combined growth of bladder urothelial
      cells and smooth muscle cells for potential use in tissue engineering techniques,
      and in vitro study of the cellular mechanisms involved in bladder regeneration.
      MATERIALS AND METHODS: Primary cultures of human bladder urothelial cells and
      smooth muscle cells were established using standard enzymatic digestion or
      explant techniques. Cultured cells were then seeded on small intestinal submucosa
      at a density of 1 x 105 cells per cm.2, incubated and harvested at 3, 7, 14 and
      28 days. The 5 separate culture methods evaluated were urothelial cells seeded
      alone on the mucosal surface of small intestinal submucosa, smooth muscle cells
      seeded alone on the mucosal surface, layered coculture of smooth muscle cells
      seeded on the mucosal surface followed by urothelial cells 1 hour later, sandwich
      coculture of smooth muscle cells seeded on the serosal surface followed by
      seeding of urothelial cells on the mucosal surface 24 hours later, and mixed
      coculture of urothelial cells and smooth muscle cells mixed and seeded together
      on the mucosal surface. Following harvesting at the designated time points small
      intestinal submucosa cell constructs were formalin fixed and processed for
      routine histology including Masson trichrome staining. Specific cell growth
      characteristics were studied with particular attention to cell morphology, cell
      proliferation and layering, cell sorting, presence of a pseudostratified
      urothelium and matrix penetrance. To aid in the identification of smooth muscle
      cells and urothelial cells in the coculture groups, immunohistochemical analysis
      was performed with antibodies to alpha-smooth muscle actin and cytokeratins
      AE1/AE3. RESULTS: Progressive 3-dimensional growth of urothelial cells and smooth
      muscle cells occurred in vitro on small intestinal submucosa. When seeded alone
      urothelial cells and smooth muscle cells grew in several layers with minimal to
      no matrix penetration. In contrast, layered, mixed and sandwich coculture methods
      demonstrated significant enhancement of smooth muscle cell penetration of the
      membrane. The layered and sandwich coculture techniques resulted in organized
      cell sorting, formation of a well-defined pseudostratified urothelium and
      multilayered smooth muscle cells with enhanced matrix penetration. With the mixed
      coculture technique there was no evidence of cell sorting although matrix
      penetrance by the smooth muscle cells was evident. Immunohistochemical studies
      demonstrated that urothelial cells and smooth muscle cells maintain the
      expression of the phenotypic markers of differentiation alpha-smooth muscle actin
      and cytokeratins AE1/AE3. CONCLUSIONS: Small intestinal submucosa supports the 3
      dimensional growth of human bladder cells in vitro. Successful combined growth of
      bladder cells on small intestinal submucosa with different seeding techniques has
      important future clinical implications with respect to tissue engineering
      technology. The results of our study demonstrate that there are important smooth
      muscle cell-epithelial cell interactions involved in determining the type of in
      vitro cell growth that occurs on small intestinal submucosa. Small intestinal
      submucosa is a valuable tool for in vitro study of the cell-cell and cell-matrix
      interactions that are involved in regeneration and various disease processes of
      the bladder.

PMID- 10958712
TI  - Regeneration of functional bladder substitutes using large segment acellular
      matrix allografts in a porcine model.
AB  - PURPOSE: We previously reported on the short-term (4 weeks) morphometric analysis
      of a large bladder acellular matrix allograft used as a bladder bioprosthesis
      (average size 24 cm.2). We demonstrated cellular repopulation through the entire
      thickness of the graft. We now present the long-term (12 weeks) morphometric
      results of graft regenerated porcine bladders using segments measuring an average
      of 40 cm.2. MATERIALS AND METHODS: Bladders harvested from pigs were subjected to
      detergent and enzymatic extractions to render them acellular. Partial cystectomy
      was performed in 21 pigs and the defect was repaired with a bladder acellular
      matrix allograft (average size 40.52 cm.2). Of the animals 8 were sacrificed at
      1, 2 and 4 weeks and 13 were sacrificed at 8 and 12 weeks. To evaluate cellular
      repopulation and matrix reorganization the native bladder and graft were analyzed
      using standard histological and immunofluorescent techniques. To evaluate for
      calcium deposits in the grafts a radiological evaluation of the graft was
      performed after explantation. RESULTS: All animals survived the surgical
      procedure and there were no significant urinary leaks. No stones were noted in
      any of the bladders. At 1 week there was a diffuse infiltration with acute
      inflammatory cells. At 2 weeks the luminal surface of the graft was lined with a
      single layer of urothelium, and there was stromal infiltration with unorganized
      smooth muscle cells and angiogenesis. At 4 weeks the urothelium was multilayered
      with organizing groups of smooth muscle cells and angiogenesis. At 8 and 12 weeks
      there was repopulation throughout the bladder acellular matrix allograft implant
      with all native cellular components participating. CONCLUSIONS: We present
      evidence that large patch bladder acellular matrix allograft implantation is
      technically feasible and may prove to be a viable surgical alternative to bladder
      augmentation with intestinal segments. Its advantages may include the potential
      for complete and functional regeneration of a bladder substitute.

PMID- 10958713
TI  - Initial experience with the transurethral self-detachable balloon system for
      urinary incontinence in pediatric patients.
AB  - PURPOSE: A new endoscopic technique to treat urinary incontinence in children
      using a self-detachable balloon device was studied. MATERIALS AND METHODS: The
      study includes 11 patients with a mean age of 14.6 years and all of whom had
      intrinsic sphincter deficiency due to myelomeningocele in 9, spinal artery bleed
      in 1 and cloacal exstrophy in 1. All patients were on clean intermittent
      catheterization preoperatively and postoperatively. Endoscopic balloon treatment
      was performed on an outpatient basis. A mean of 5 balloons (range 2 to 8) were
      placed per patient. All patients underwent formal urodynamic study preoperatively
      and at 6 weeks and 6 months following balloon placement. RESULTS: Of the 9
      patients without prior bladder neck surgery 7 had improvement in urodynamic
      parameters, including urethral pressure profile in all 7 and functional bladder
      capacity in 6, 4 were markedly improved clinically and 2 were dry. Two patients
      with prior bladder neck surgery were clinically unchanged following balloon
      placement, although 1 had urodynamic improvement. CONCLUSIONS: Our initial
      experience with the transurethral self-detachable balloon system as a minimally
      invasive outpatient procedure to treat urinary incontinence in children has been
      encouraging. To date this procedure appears most applicable to the patient who
      has not undergone surgery and has a neurogenic etiology for urinary incontinence.

PMID- 10958714
TI  - Outcome of gastrocystoplasty in tertiary pediatric urology practice.
AB  - PURPOSE: Although the use of stomach for bladder reconstruction has become
      popular during the last decade, it is not a panacea. We review our experience
      with gastrocystoplasty. MATERIALS AND METHODS: We completed a retrospective chart
      review of 11 females and 12 males, 1.5 to 22.5 years old (mean age 10) who
      underwent gastrocystoplasty at Hopital Sainte-Justine, Montreal, Quebec and
      Children's Hospital, Winnipeg, Manitoba, Canada between December 1990 and 1998.
      Primary diagnoses included spinal dysraphism in 14 patients, posterior urethral
      valves in 3, cloacal exstrophy in 2, cloacal outlet anomaly in 2, multiple failed
      ureteral reimplantations with bladder dysfunction in 1 and neurogenic bladder of
      uncertain etiology in 1. Three patients presented with chronic renal failure.
      Concurrent reconstructive surgery included ureteral reimplantation in 10
      patients, bladder neck plasty in 4 or closure in 4, and continent urinary
      diversion in 5. RESULTS: Acute postoperative complications included urosepsis in
      2 cases, bowel obstruction in 2 and ureteral obstruction in 1. Followup ranged
      from 4 to 86 months (mean 45). Long-term complications consisted of intractable
      hematuria-dysuria syndrome in 5 cases, inability to catheterize in 3, perineal
      urinary fistula in 2, new onset hydronephrosis in 2, continent stomal stenosis in
      1 and bladder calculus in 1. Proton pump inhibitors and/or histamine 2
      antagonists were used in 16 of the 23 patients to prevent the hematuria-dysuria
      syndrome. In 5 cases the hematuria-dysuria syndrome was poorly controlled
      medically and 3 were converted to another form of urinary reconstruction. In 18
      of 20 cases voiding cystourethrography revealed no vesicoureteral reflux, and in
      18 of 21 ultrasound documented stable or improved upper tracts. Socially
      acceptable urinary continence was attained in 19 of the 21 patients. CONCLUSIONS:
      The use of stomach for bladder augmentation may be considered in patients with
      cloacal exstrophy and/or metabolic acidosis. Histamine blockers and/or proton
      pump inhibitors may be required to prevent the hematuria-dysuria syndrome.
      Symptoms of the hematuria-dysuria syndrome may be disabling and may mandate
      alternative forms of urinary tract reconstruction.

PMID- 10958715
TI  - In vitro engineering of human stratified urothelium: analysis of its morphology
      and function.
AB  - PURPOSE: Gastric or intestinal patches, commonly used for reconstructive
      cystoplasty, may induce severe metabolic complications. The use of bladder
      tissues reconstructed in vitro could avoid these complications. We compared
      cellular differentiation and permeability characteristics of human native with in
      vitro cultured stratified urothelium. MATERIALS AND METHODS: Human stratified
      urothelium was induced in vitro. Morphology was studied with light and electron
      microscopy and expression of key cellular proteins was assessed using
      immunohistochemistry. Permeability coefficients were determined by measuring
      water, urea, ammonia and proton fluxes across the urothelium. RESULTS: As in
      native urothelium the stratified urothelial construct consisted of basal membrane
      and basal, intermediate and superficial cell layers. The apical membrane of
      superficial cells formed villi and glycocalices, and tight junctions and
      desmosomes were developed. Immunohistochemistry showed similarities and
      differences in the expression of cytokeratins, integrin and cellular adhesion
      proteins. In the cultured urothelium cytokeratin 20 and integrin subunits alpha6
      and beta4 were absent, and symplekin was expressed diffusely in all layers.
      Uroplakins were clearly expressed in the superficial umbrella cells of the
      urothelial constructs, however, they were also present in intermediate and basal
      cells. Symplekin and uroplakins were expressed only in the superficial cells of
      native bladder tissue. The urothelial constructs showed excellent viability, and
      functionally their permeabilities for water, urea and ammonia were no different
      from those measured in native human urothelium. Proton permeability was even
      lower in the constructs compared to that of native urothelium. CONCLUSIONS:
      Although the in vitro cultured human stratified urothelium did not show complete
      terminal differentiation of its superficial cells, it retained the same barrier
      characteristics against the principal urine components. These results indicate
      that such in vitro cultured urothelium, after being grown on a compliant
      degradable support or in coculture with smooth muscle cells, is suitable for
      reconstructive cystoplasty.

PMID- 10958716
TI  - Erectile dysfunction in patients with spina bifida is a treatable condition.
AB  - PURPOSE: Now that individuals with spina bifida live well into adulthood erectile
      dysfunction has become a recognized associated medical disorder. To our knowledge
      no study has dealt specifically with treatment of erectile dysfunction in men
      with spina bifida. Therefore, we conducted a prospective, blinded, randomized,
      placebo controlled, dose escalation, crossover study to determine the ability to
      treat erectile dysfunction in men with spina bifida with sildenafil citrate.
      MATERIALS AND METHODS: Erectile dysfunction was diagnosed in 15 men 19 to 35
      years old with spina bifida who were assigned to take 4 sets of tablets, 5
      tablets per set, in a random order. All patients took 25 and 50 mg. sildenafil
      and 2 identical looking sets of corresponding placebos 1 hour before planned
      sexual activity. Efficacy was assessed by the effect of treatment compared to
      baseline, that is before treatment, on rating of erections (scored from 0 to 10),
      duration of erections, frequency of erections based on response to question 1
      (scored from 0 to 5) of the International Index of Erectile Function and
      confidence to obtain an erection based on response to question 15 (scored from 1
      to 5) of the International Index of Erectile Function. RESULTS: Improved erectile
      function was reported while on sildenafil by 12 (80%) men compared to baseline
      and placebos. There was a significant dose dependent improvement of erectile
      function with both 25 and 50 mg. sildenafil compared to baseline (p <0.05), as
      mean erectile score increased by 50% and 88%, mean duration of erections
      increased by 192% and 266%, mean frequency of erections increased by 61% and 96%,
      and mean level of confidence increased by 33% and 63%, respectively. Furthermore,
      50 mg. sildenafil provided greater improvement in all 4 parameters compared to 25
      mg. The placebo results were not significantly different compared to baseline for
      any of the parameters. CONCLUSIONS: Erectile dysfunction in patients with spina
      bifida is a medically treatable condition. Sildenafil is effective in this
      patient population and improves level of sexual confidence.

PMID- 10958718
TI  - Intravesical electrostimulation in pediatric patients with spinal cord defects.
AB  - PURPOSE: Creating a low pressure continent urinary storage mechanism for the
      pediatric patient with neurogenic bladder is difficult. Current therapy, which is
      enterocystoplasty with intermittent catheterization, is not an ideal solution. In
      an effort to optimize storage we used intravesical electrostimulation in patients
      with spinal cord defects. MATERIALS AND METHODS: A retrospective review of all
      pediatric patients undergoing bladder stimulation was performed. Parameters
      reviewed included indication, patient age, initial age adjusted pressure specific
      bladder volume (less than 30 cm. H2O), initial leak point pressure, number of
      treatments, number of sessions per treatment, posttreatment age adjusted pressure
      specific bladder volume, voiding and continence status. RESULTS: Records of all
      44 patients treated were reviewed. Indications for treatment included decreasing
      bladder storage pressures in 24 cases, increased continence between
      catheterization in 13 and achieving volitional voiding in 7. Patients who became
      continent had similar age at initiation of treatment, number of treatments,
      number of sessions, initial leak point pressure and final age adjusted pressure
      specific bladder volume compared to nonresponders. Nonresponders required
      surgical intervention to achieve continence with safe storage pressures. Overall,
      16% (7 of 44) of patients were continent with safe storage pressures at the
      completion of treatment and 9% (4 of 44) achieved pretreatment goals.
      CONCLUSIONS: While some high risk patients were spared surgery due to
      intravesical electrostimulation, most were not. Spontaneous voiding to completion
      at safe pressures was not achieved. We were unable to clarify before treatment
      which patients would benefit from intravesical electrostimulation.

PMID- 10958717
TI  - Urological outcome of patients with cervical and upper thoracic myelomeningocele.
AB  - PURPOSE: We determined the incidence of voiding disorders and upper tract
      deterioration in children with cervical and upper thoracic level
      myelomeningocele. MATERIALS AND METHODS: We retrospectively reviewed the
      neurosurgical and urological presentation, evaluation and treatment of 11
      patients of whom 8 had cervical and 3 had upper thoracic myelomeningocele. There
      were 7 female and 4 male patients 10 months to 39 years old (mean age 12 years).
      All patients were ambulatory and 5 of 11 (45%) had hydrocephalus. Although a
      voiding history was obtained by a neurosurgeon in all patients, only 9 had
      undergone a formal urological evaluation, including video urodynamic assessment
      in 5. RESULTS: No patient had an increased post-void residual and none had ever
      been placed on intermittent catheterization. Tethered spinal cords from caudal
      fixation (thickened filum terminale and a lipomyelomeningocele) were present in 2
      patients with urinary incontinence of whom 1 had recurrent cystitis. Imaging
      studies of the upper tracts were normal in all 9 patients and video urodynamics
      were normal in 3 of 5. No patient has required urological operative intervention.
      CONCLUSIONS: To our knowledge, this study represents the largest reported series
      of patients with cervical and upper thoracic myelomeningocele who have undergone
      urological evaluation. Our experience suggests that patients with cervical and
      upper thoracic myelomeningocele have a low risk of voiding disorders and upper
      tract deterioration unless other conditions, such as a congenital tethered cord,
      are present. Additional reports of children with cervical and upper thoracic
      myelomeningocele are necessary to confirm these findings.

PMID- 10958719
TI  - Electrically stimulated detrusor myoplasty.
AB  - PURPOSE: Many children with spina bifida and other causes of neurogenic bladder
      rely on clean intermittent catheterization to empty the hyporeflexic or areflexic
      bladder. Direct bladder and sacral nerve root stimulation have been met with
      limited success. We studied the electrical stimulation of a rectus abdominis
      muscle flap wrapped around the bladder to achieve bladder contractility and
      emptying. MATERIALS AND METHODS: The feasibility of performing rectus detrusor
      myoplasty in humans was first studied in 8 cadavers. In male and female cadavers
      it was possible to wrap the distended bladder completely with the rectus
      abdominis muscle. The rectus abdominis muscle was surgically dissected with
      preservation of its insertion on the pubis bone and rotation of its mid section
      behind the bladder to effect a complete bladder wrap. The deep inferior
      epigastric artery and veins, and 2 most caudal intercostal nerves were preserved.
      This unilateral rectus abdominis muscle flap was then electrically stimulated
      with 2 pairs of bipolar electrodes inserted into the muscle near the nerve
      entrance. Stimulation frequencies of 40, 60 and 80 Hz. were used in each of the 8
      dogs. The increase in intravesical pressure over baseline, compliance and post
      void residual were measured. Paired Student's t tests were used for statistical
      comparisons. RESULTS: The increase in intravesical pressure ranged 35 +/- 5 to 45
      +/- 7 cm. H2O at stimulation frequency 40 and 80 Hz., respectively. Post-void
      residual was 27 +/- 4%, 22 +/- 3% and 26 +/- 3% at stimulation frequencies 40, 60
      and 80 Hz., respectively. Intravesical pressure was significantly increased over
      baseline bladder pressure (p <0.05). CONCLUSIONS: Electrically stimulated
      detrusor myoplasty results in uniform increases in intravesical pressure and
      reasonable bladder emptying in an animal model. We are currently investigating
      detrusor myoplasty in a chronic study to determine whether it can be used for
      enhanced bladder emptying in children with poor detrusor contractility.

PMID- 10958720
TI  - Modification of the Koyanagi technique for the single stage repair of proximal
      hypospadias.
AB  - PURPOSE: We describe a modification of the Koyanagi technique for hypospadias.
      Use of opposing parameatal-based skin flaps that extend distally to incorporate
      the inner layer of the prepuce was modified to preserve blood supply to the flaps
      in an attempt to reduce complications and improve results. MATERIALS AND METHODS:
      During the last 7 years 20 boys underwent treatment of proximal hypospadias using
      the modified hypospadias repair. RESULTS: Cosmetic and functional, long-term
      (mean 34 months) results were excellent. Complications consisted of 4
      urethrocutaneous fistulas (20%). There were no instances of meatal stenosis,
      diverticulum or urethral stricture. CONCLUSIONS: The modified technique permits 1
      stage repair of proximal hypospadias with a low complication rate.

PMID- 10958721
TI  - Anatomy of the neurovascular bundle: is safe mobilization possible?
AB  - PURPOSE: We have previously defined the anatomy of the neurovascular bundle in
      the normal and hypospadiac penis. Historical experience suggests that
      mobilization of the neurovascular bundle is anatomically possible. We attempt to
      prove whether mobilization of the neurovascular bundle is safe and theoretically
      sound. Specific questions that will be addressed are does the neurovascular
      bundle send perforating branches into the corporal bodies; how far lateral does
      the dissection need to be before nerves are injured and exactly how deep into
      Buck's fascia must one go. MATERIALS AND METHODS: A total of 35 normal human
      fetal penile specimens, gestational age 8 to 35 weeks, and 3 hypospadiac
      specimens, 33 to 41 weeks of gestation, were serially sectioned and stained with
      Mason's trichrome and the neuronal markers PGP 9.5 or S100. Computer
      reconstruction using commercial software and National Institutes of Health
      imaging allowed 3-dimensional analysis of the nerves, corporal bodies and glans.
      RESULTS: Perforating nerves into the erectile bodies were not documented along
      the dorsal or lateral aspect of the tunica in any of the specimens studied. Only
      in the area of the crural bodies on the ventral lateral surface were nerves noted
      to pierce into erectile tissue. The neural network was extensive from the 11 and
      1 to the 5 and 7 o'clock positions corresponding to the erectile tissue and
      urethral spongiosum junction. At this junction minor nerve branches were noted to
      perforate into the urethral spongiosum. A microscopic plane exists between the
      neurovascular bundle and tunica of the corporal bodies measuring 20 to 30 micro.
      in specimens greater than 30 weeks in gestation. CONCLUSIONS: Perforating
      branches from the dorsal lateral neurovascular bundle do not exist based on
      serial step sectioning and microscopic examination of male genital specimens.
      Surgically it is possible to elevate the neurovascular bundle but the dissection
      needs to remain directly on top of the tunica albuginea to prevent neuronal
      injury. Small perforating branches into the urethral spongiosum may be injured
      with unknown significance. We continue to advocate plication in the nerve-free
      zone at the 12 o'clock position for correction of penile curvature.

PMID- 10958722
TI  - A prospective randomized trial of dressings versus no dressings for hypospadias
      repair.
AB  - PURPOSE: Dressings following hypospadias repair have the benefits of gentle
      compression for hemostasis, immobilization of the wound and formation of a
      "hermetic seal." Potential disadvantages include producing ischemia, infection
      and pain during dressing removal. We compare the success and complications of
      hypospadias repair with and without dressings in a prospective randomized manner.
      MATERIALS AND METHODS: Children with hypospadias were randomized either to
      receive or not receive a transparent film dressing for 2 days. A written informed
      consent was obtained. Hypospadias repair was performed in 100 consecutive
      patients. Study exclusion criteria were known coagulopathy and oozing at the end
      of the case. Criteria for success were a glanular meatus, single forward directed
      stream, unimpeded voiding, absence of penile chordee, good cosmesis and no need
      for any secondary procedure. All but 1 hypospadias repair preserved the integrity
      of the urethral plate. Statistical significance was considered at p <0.05.
      RESULTS: We were able to randomize between the dressed and nondressed groups
      based on fresh versus redo cases, position of the urethral meatus, severity of
      chordee, use of epinephrine, duration of surgery, type of repair and chordee
      correction (p >0.05). Of 49 patients 44 (90%) had successful results in the
      dressed and nondressed groups. Postoperative calls were more common in the
      undressed group (p = 0.02) but no particular complication was more common in
      either group (p >0.05). Mean followup was 1 year, and there was no clinical or
      statistical difference between the dressed and nondressed groups with regard to
      success of the operation (p >0.05). CONCLUSIONS: The success rate for hypospadias
      surgery that preserves the urethral plate is independent of dressing usage.
      Dressings may not be indicated for all hypospadias repairs.

PMID- 10958723
TI  - How accurate is the prenatal diagnosis of abnormal genitalia?
AB  - PURPOSE: The prenatal diagnosis of abnormal genitalia may have a major impact on
      prenatal counseling and postnatal outcome. We studied the accuracy and clinical
      implications of the prenatal diagnosis of abnormal genitalia. MATERIALS AND
      METHODS: Between 1991 and 1999 the prenatal and/or postnatal diagnosis of
      abnormal genitalia in 53 cases was made at our institution. All cases were
      prenatally assessed at our Obstetrics and Fetal Medicine Department. Outcome was
      confirmed postnatally or by a fetopathologist in the case of pregnancy
      termination. RESULTS: A genital anomaly was prenatally diagnosed in 43 cases and
      was accurate in 34, while in 9 cases anomalies were absent at birth. In 10 cases
      ambiguous genitalia were not detected prenatally. The primary anomalies suspected
      were male pseudohermaphroditism in 19 cases and female pseudohermaphroditism in
      12, including 2 cases of congenital adrenal hyperplasia. Male
      pseudohermaphroditism was detected prenatally in 17 cases and diagnosis was
      confirmed at birth. Female pseudohermaphroditism was detected prenatally in 12
      cases and only 5 were confirmed and the anomaly was discovered at birth in 6. The
      prognosis was highly altered when many malformations or aneuploidy was associated
      with ambiguous genitalia. Of the 15 patients with many malformations only 3
      survived, and pregnancy was terminated in 3 of 4 cases of aneuploidy.
      CONCLUSIONS: When pseudohermaphroditism was detected in a male fetus by an
      experienced ultrasonographer at a tertiary center the prenatal diagnosis was
      accurate in 100% of cases. The prenatal diagnosis was less accurate (46% correct)
      in a female fetus.

PMID- 10958724
TI  - Histology of the urethral plate: implications for hypospadias repair.
AB  - PURPOSE: We define the histology of the urethral plate in boys with hypospadias.
      MATERIALS AND METHODS: Subepithelial biopsies of the urethral plate were obtained
      in 17 boys, including 13 with distal and 4 with penoscrotal hypospadias. Ventral
      penile curvature was noted in 5 cases. Specimens were evaluated by 7 light
      microscopy after hematoxylin and eosin staining. RESULTS: All biopsies
      demonstrated well vascularized connective tissue comprised of smooth muscle and
      collagen. There was no evidence of fibrous bands or dysplastic tissue.
      CONCLUSIONS: The urethral plate consists of epithelium overlying connective
      tissue. We found no histological evidence of fibrous cords historically
      considered responsible for chordee.

PMID- 10958725
TI  - Glanuloplasty and in situ tubularization of the urethral plate: long-term
      followup.
AB  - PURPOSE: We update our experience with glanuloplasty and in situ tubularization
      of the urethral plate for hypospadias repair first described in 1995, and report
      its indications and long-term results. MATERIALS AND METHODS: We evaluated the
      surgical results of glanuloplasty and in situ tubularization of the urethral
      plate for hypospadias repair in 308 patients. RESULTS: Overall cosmetic results
      were excellent. The overall complication rate for both series was 9.7%, and
      complications consisted of a urethral fistula in 9.1% and a urethral diverticulum
      in 0.6%. However, in our recent series the complication rate decreased to 1.7%
      for distal repairs and 7.7% for mid shaft hypospadias repair. CONCLUSIONS:
      Glanuloplasty with in situ tubularization of the urethral plate is an excellent
      technique for the majority of boys with distal and mid shaft hypospadias,
      producing a pleasing cosmetic appearance with a low complication rate.

PMID- 10958726
TI  - Correction of penoscrotal transposition: a novel approach.
AB  - PURPOSE: Penoscrotal transposition is a rare anomaly resulting in a partial or
      complete positional exchange between the penis and the scrotum. Time-honored
      repairs of penoscrotal transposition rely on the creation of rotational flaps to
      mobilize the scrotum. We offer a radically different approach to this anomaly by
      transposing the penis and not the scrotum to its normal anatomical location.
      MATERIALS AND METHODS: Transposition of the penis was performed in 15 patients.
      The penis is degloved followed by correction of the chordee. A suprapubic
      buttonhole is created in an anatomically correct location for the penis. The
      degloved phallus is then delivered into this buttonhole. The shaft skin is
      mobilized and transposed to resurface the penile shaft. A midline scrotoplasty
      completes the first stage. The scrotum is never transposed and scrotal rotational
      flaps are unnecessary. RESULTS: All 15 patients have had an excellent cosmetic
      outcome. There have been no cases of vascular compromise to the shaft or scrotal
      skin. CONCLUSIONS: This novel approach produces superior cosmetic results and
      should be used in all cases of penoscrotal transposition.

PMID- 10958727
TI  - Further experience with the double onlay preputial flap for hypospadias repair.
AB  - PURPOSE: Severe hypospadias can be safely and reliably repaired in 1 stage using
      island flaps of preputial skin. However, problems with conventional techniques
      include penile asymmetry resulting from rotation of the vascular pedicle around 1
      side of the penile shaft and at times doubtful viability of the Byars flaps used
      for ventral skin coverage. We describe how some of these problems can be resolved
      using the double onlay preputial flap for hypospadias repair. MATERIALS AND
      METHODS: We reviewed the records of 47 children who underwent 1-stage double
      onlay preputial flap hypospadias repair at our institution between June 1994 and
      July 1998. Patient age ranged from 6 months to 9 years (mean 12.2 months). The
      urethral meatus was at the midshaft in 12 patients (25%), penoscrotal in 30 (64%)
      and perineal in 5 (11%). Chordee repair required dorsal plication in 29 patients,
      7 of whom required an additional ventral incision of the tunica albuginea and
      tunica vaginalis autograft with preservation of the urethral plate to complete
      the repair. Scrotal transposition and bifid scrotum were repaired at the time of
      hypospadias repair in 9 patients. RESULTS: Followup was 3 to 47 months (mean 15.2
      months). Complications requiring reoperation occurred in 12 patients (25%). In 8
      (17%) boys a fistula developed, of whom 6 had perineal and 2 had penoscrotal
      hypospadias. Fistula closure was required in all patients. Successful closure was
      achieved with 1 procedure in 6 patients, required an additional fistula repair in
      1 and remains to be determined in 1. Diverticula, meatal recession and persistent
      penile curvature requiring repeat dorsal plication occurred in 4 (9%), 2 (4%) and
      2 (4%) patients, respectively. Revision for a bulky ventral skin strip was
      required in 1 boy (2%). All complications occurred in patients with the more
      proximal hypospadias. CONCLUSIONS: The double onlay preputial flap technique for
      hypospadias repair offers good cosmetic and functional results. Given the high
      incidence of penoscrotal and perineal hypospadias (75%) in our series
      complication rates are comparable or better than those of other techniques.

PMID- 10958728
TI  - Defunctionalized bladders: effects before and after refunctionalization in an
      animal model.
AB  - PURPOSE: Bladder behavior after refunctionalization is usually unpredictable. We
      comparatively analyze various aspects of bladder defunctionalization and
      subsequent refunctionalization using an animal model. MATERIALS AND METHODS: A
      total of 18 rabbits were divided equally into 3 groups. Animals in group 1
      underwent 2 successive surgical procedures, including bladder division and
      reattachment. Bladder division was performed by hemisecting the bladder from dome
      to trigone into a functioning and nonfunctioning chamber. Bladder reattachment
      was achieved by reanastomosing both hemibladders. Group 2 animals underwent sham
      operations, and group 3 animals were age matched normal controls. Serial
      urodynamic studies and fluoroscopic cystograms were performed in all animals.
      Gross, histochemical (hematoxylin and eosin, Masson's trichrome and Sirius red)
      and immunocytochemical (alpha-actin, collagen I and III) analyses, collagen
      content determination and organ bath studies were performed. RESULTS: The
      defunctionalized hemibladders demonstrated lower wet weight, capacity and
      compliance compared to the functional contralateral and normal control bladders.
      Refunctionalization of the bladders resulted in a progressive recovery of
      capacity and compliance with time. The bladder contractile response and
      connective tissue-to-muscle ratio were abnormal in the defunctionalized segments
      but normalized after bladder refunctionalization. CONCLUSIONS:
      Defunctionalization results in remarkable alterations in bladder growth,
      capacity, compliance and distribution of connective tissue. However, these
      bladders demonstrate an innate capacity to recover from these alterations
      following refunctionalization.

PMID- 10958729
TI  - The role of hypercalciuria in a subgroup of dysfunctional voiding syndromes of
      childhood.
AB  - PURPOSE: Idiopathic hypercalciuria is believed to be the cause of a variety of
      urinary tract complaints in clinical pediatrics, including urinary frequency,
      urgency, and/or dysuria, often associated with gross or microscopic hematuria. In
      children noncalculous manifestations of idiopathic hypercalciuria are reportedly
      more common than urolithiasis. We determine the use of the calcium-to-creatinine
      ratio for the evaluation of different subsets of functional voiding disorders.
      MATERIALS AND METHODS: We retrospectively evaluated 288 patients with functional
      voiding disorders during the last 8 years. Patients presenting with isolated
      urinary tract infection were not included in the study. A thorough history with
      emphasis on voiding patterns was elicited and a routine urinalysis was performed
      in all patients. Patients were divided into 5 groups of 22 with total gross
      hematuria and dysfunctional voiding pattern, 102 with microhematuria and
      dysfunctional voiding pattern, 66 with isolated childhood daytime frequency, 45
      with the isolated dysuria syndrome and 53 with combined childhood frequency
      urgency-dysuria syndrome. The season at presentation was noted to determine a
      seasonal pattern. In 149 patients urine was evaluated for a spot calcium-to
      creatinine ratio. RESULTS: Mean age of the 95 (33%) males and 193 (67%) females
      was 6.1 years (range 2 to 14) and mean duration of symptoms was 10 months (1 week
      to 10 years). The incidence of idiopathic hypercalciuria was 28% in cases with
      gross hematuria and dysfunctional voiding, 30% with microscopic hematuria and
      dysfunctional voiding, 21% with pure childhood daytime frequency, 22% with pure
      dysuria, and 28% with frequency, urgency and dysuria. The patients were treated
      predominantly with behavioral therapy, correction of faulty voiding habits,
      anticholinergics and minor diet modification in some. Mean followup of 6.5 months
      (range 1 month to 10 years) was available for 153 patients (53%). Resolution of
      symptoms along with marked improvement in voiding habits was noted in 136 (89%)
      patients, moderate improvement in 10 (6.5%) and persistent symptoms with minimal
      improvement in 7 (4.5%). Treatment with thiazides was used in only 6 (2%)
      patients who had intractable symptoms and a markedly elevated urine calcium-to
      creatinine ratio of whom 5 responded favorably. CONCLUSIONS: Idiopathic
      hypercalciuria may have a significant role in cases of functional voiding
      disorders. It affects the different subsets of voiding disorders with remarkable
      consistency but the exact mechanism remains unknown. Although a significant
      number of patients with voiding dysfunction have an elevated calcium-to
      creatinine ratio, the majority respond to standard behavioral therapy and
      pharmacotherapy in the form of anticholinergics, and treatment directed toward
      hypercalciuria is not required in most cases.

PMID- 10958730
TI  - The dysfunctional voiding scoring system: quantitative standardization of
      dysfunctional voiding symptoms in children.
AB  - PURPOSE: Academic research on pediatric nonneurogenic voiding dysfunction has
      long been hampered by the lack of a standardized reporting system for voiding
      symptoms. We evaluated the performance of a newly devised, objective instrument
      to quantify or grade the severity of abnormal voiding behaviors of children.
      MATERIALS AND METHODS: There were 10 voiding dysfunction parameters that were
      assigned scores of 0 to 3 according to prevalence, and possible total scores
      ranged from 0 to 30. The Dysfunctional Voiding Symptom Score was completed by 2
      groups of patients. Group 1 consisted of patients 3 to 10 years old presenting to
      the pediatric urology clinic with a history of diurnal urinary incontinence,
      urinary tract infections or abnormal voiding habits. Group 2 consisted of an age
      matched cohort with no history of urological complaints presenting to hospital
      clinics outside of urology. Patients diagnosed with organic or anatomical
      disease, such as posterior urethral valves or meningomyelocele, were excluded
      from our analysis. RESULTS: Group 1 consisted of 104 patients (female-to-male
      ratio 4:1) with a median symptom score of 14 and group 2 consisted of 54 patients
      (female-to-male ratio 1.3:1) with a median score of 4. The dysfunctional voiding
      odds ratio was 2.93 for females compared to that of males. Using receiver
      operating characteristics the optimum cutoff score was 6.026 (sensitivity 92.77%
      and specificity 87.09%) for females and 9.02 (sensitivity of 80.95% and
      specificity of 91. 30%) for males. In addition, we found certain questions to be
      more reflective than others of dysfunctional voiding symptoms in our population.
      CONCLUSIONS: The Dysfunctional Voiding Symptom Score appears to provide accurate
      and objective, that is, numerical, grading of voiding behaviors of children.
      Comparative research studies of dysfunctional voiding diagnosis and response to
      therapy as well as objective measurements of treatment efficacy and outcomes
      analysis should be aided greatly by this system.

PMID- 10958731
TI  - Angiogenesis and neuroblastomas: interleukin-8 and interleukin-8 receptor
      expression in human neuroblastoma.
AB  - PURPOSE: Studies have demonstrated that the pro-angiogenic cytokine interleukin-8
      (IL-8) and the IL-8 receptors likely have a role in the growth and metastasis of
      various solid tumors. We hypothesized that in vivo neuroblastoma expresses IL-8
      and the IL-8 receptors A and B, and that factors known to regulate IL-8
      expression are present and active in the neuroblastoma microenvironment.
      MATERIALS AND METHODS: To confirm the presence of IL-8/IL-8 receptors in
      neuroblastoma, immunohistochemical analysis for IL-8 and its receptors was
      performed on 10 archival specimens, including benign adrenal and well to poorly
      differentiated neuroblastoma samples. Immunohistochemical analysis was also
      performed for interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha.
      Cultured neuroblastoma cells SK-N-MC and SK-N-SH were stimulated with 10 ng./ml.
      IL-1beta or tumor necrosis factor-alpha and control media (15 each). Cell culture
      supernatants were analyzed with enzyme-linked immunosorbant assay for IL-8 levels
      at 24 and 48 hours. RESULTS: Minimal expression of IL-8 was noted in benign
      adrenal tissue but expression for IL-8 was present in all neuroblastoma
      specimens. Microvessel staining was present in 30% of the specimens. All tumor
      specimens expressed IL-8 receptor B, and both receptors were expressed in the
      tumor microvasculature. Immunohistochemical analysis confirmed the presence of IL
      1beta and tumor necrosis factor in the neuroblastoma microenvironment. In vitro
      studies demonstrated that SK-N-MC and SK-N-SH cells express low levels of IL-8
      under normal conditions and that IL-1beta and tumor necrosis factor-alpha
      significantly increased expression of IL-8 at 24 and 48 hours. CONCLUSIONS: Our
      results indicate that IL-8 and its receptors are expressed in neuroblastoma tumor
      specimens. In addition, the fact that IL-1beta and tumor necrosis factor-alpha
      are expressed in the neuroblastoma microenvironment combined with our in vitro
      results suggests that these cytokines may be involved in in vivo regulation of IL
      8 in human neuroblastoma. Understanding the angiogenic factors and regulatory
      cascade promoting angiogensis in neuroblastoma may lead to the development of
      effective anti-angiogenic strategies.

PMID- 10958732
TI  - Changes in bladder contractility and compliance due to urethral obstruction: a
      longitudinal followup of guinea pigs.
AB  - PURPOSE: We established the longitudinal changes in bladder contractility and
      compliance as a result of urethral obstruction using a guinea pig model.
      MATERIALS AND METHODS: Obstruction was induced in guinea pigs by a silver ring
      around the urethra. Urodynamic studies were performed longitudinally in
      individual animals. Bladder contractility and compliance were calculated from the
      measured bladder pressure and urine flow rate. RESULTS: Bladder contractility
      developed in distinct phases. It reached a maximum 200% increase after an average
      of 3.25 weeks concomitant with an almost 2-fold increase in urethral resistance,
      remained 150% to 200% increased during weeks 4 to 7 and then decreased to
      starting levels again, while urethral resistance remained almost 2-fold
      increased. Bladder compliance decreased by 80% during the first 3 weeks and
      continued to decrease to 5% of its original value after 10 to 11 weeks.
      CONCLUSIONS: Our data indicate that as a result of obstruction bladder function
      passes through a specific sequence of stages, including first a compensatory
      increase in contractility, then a stabilization phase and finally a
      decompensation state. In contrast bladder compliance shows a continuous decrease.
      The data suggest that for assessing how far a bladder has deteriorated due to
      obstruction a combination of functional and structural data may be warranted.

PMID- 10958733
TI  - The decompensated detrusor III: impact of bladder outlet obstruction on
      sarcoplasmic endoplasmic reticulum protein and gene expression.
AB  - PURPOSE: Regulation of calcium ion homeostasis has a significant role in smooth
      muscle contractility. The sarcoplasmic endoplasmic reticulum, calcium, magnesium,
      adenosine triphosphatase (SERCA) is a regulatory ion pump that may have a role in
      the functional outcome after outlet obstruction. We investigate what correlation
      if any existed between SERCA protein and gene expression, and the contractile
      properties in the same bladder. MATERIALS AND METHODS: Standardized partial
      bladder outlet obstructions were created in adult New Zealand white rabbits,
      which were divided into control, sham operated and obstructed groups. Muscle
      strip studies subcategorized the obstructed group into compensated (force greater
      than 50% of control) and decompensated (force less than 50% of control).
      Microsomal membrane and total RNA fractions were prepared from the same bladder
      tissue. Membrane proteins were used for Western blot analysis using a SERCA
      specific monoclonal antibody, and total RNA was assessed with Northern blot
      analysis. RESULTS: The relative intensities of signals for the Western and
      Northern blots demonstrated a strong correlation between protein and gene
      expression. Furthermore there was a strong association between the loss of SERCA
      messenger RNA and protein expression and loss of bladder function. CONCLUSIONS:
      Bladder contractility after outlet obstruction is influenced in part by smooth
      muscle cell ability to maintain calcium homeostasis via SERCA. The loss of SERCA
      protein expression is mediated by down-regulation in gene expression in the same
      bladder. These data suggest that smooth muscle ion pump gene expression is in
      part mechanically (pressure work) regulated.

PMID- 10958734
TI  - Does neonatal pyeloureterostomy worsen bladder function in children with
      posterior urethral valves?
AB  - PURPOSE: We determine whether long-term bladder dysfunction is more frequent in
      children with posterior urethral valves who undergo early supravesical urinary
      diversion (pyeloureterostomy) than in those who undergo valve ablation. MATERIALS
      AND METHODS: Urodynamic studies were performed in 59 boys with severe posterior
      urethral valves who were divided into 2 groups based on initial treatment of
      valve ablation (30) and bilateral pyeloureterostomy (29). RESULTS: Of the 59 boys
      25 (42%) had a normal bladder, including 11 with an over distended bladder and 34
      (58%) had bladder dysfunction, including instability in 22, poor compliance in 9
      and myogenic failure in 3. Of the 30 boys initially treated with valve ablation
      14 (46.6%) had a normal bladder, including 7 with an over distended bladder and
      16 (53.4%) had bladder dysfunction, including instability in 10, poor compliance
      in 4 and myogenic failure in 2. Of the 29 boys initially treated with temporary
      bilateral pyeloureterostomy 11 (38%) had normal bladders, 4 with an over
      distended bladder and 18 (62%) had bladder dysfunction, including instability in
      12, poor compliance in 5 and myogenic failure in 1. There were no statistically
      significant differences in the number or type of bladder dysfunction between the
      diversion and valve ablation groups. CONCLUSIONS: Therefore, temporary
      pyeloureterostomy did not affect bladder function adversely in the long term.

PMID- 10958735
TI  - Total urogenital complex mobilization in female patients with exstrophy.
AB  - PURPOSE: Female bladder exstrophy/epispadias has traditionally been approached in
      a staged fashion. This approach results in a vagina that remains in an abnormal
      position on the anterior abdominal wall. We present a surgical correction of the
      female exstrophy/epispadias urogenital complex with total mobilization that
      returns the vagina to its proper anatomical position. MATERIALS AND METHODS:
      Since 1997, 7 female patients presenting with variants of the
      exstrophy/epispadias complex have undergone surgical repair using total
      urogenital complex mobilization. Of the patients 1 newborn and 2 school-age
      children had classic bladder exstrophy, 2 school-age children had cloacal
      exstrophy and 2 school-age children had primary epispadias. Total urogenital
      complex mobilization involved treatment of the urethra and vagina as a single
      unit. Complete disassembly of the pelvic diaphragm or floor anterior to the
      rectum was required to reposition the urethra and vagina to their proper
      anatomical positions in the perineum. The pelvic diaphragm was then reconstructed
      anterior to the urogenital complex to recapitulate the normal female pelvic floor
      anatomy. RESULTS: All patients have an anatomically correct position of the
      urogenital complex. All the vaginas reached the perineum without the need for
      skin flaps. All patients have adequate vaginal caliber without evidence of
      stenosis. CONCLUSIONS: The female with exstrophy/epispadias has unique anatomical
      defects in the urogenital complex that require special attention. Anterior
      displacement of the bladder, urethra and vagina with concomitant lack of
      development of the anterior pelvic floor musculature make a single stage, total
      urogenital complex mobilization repair ideal for this population. The results of
      this technique have been functionally and cosmetically pleasing. Whether
      repositioning the urogenital complex into the normal anatomical position will
      improve bladder dysfunction and urinary continence rates, and decrease or
      eliminate the need for future surgery will only be known after further long-term
      followup has been completed.

PMID- 10958736
TI  - The modified Cantwell-Ransley repair for exstrophy and epispadias: 10-year
      experience.
AB  - PURPOSE: We evaluate our experience with the modified Cantwell-Ransley epispadias
      repair technique to determine the complications and long-term results. MATERIALS
      AND METHODS: The modified Cantwell-Ransley epispadias repair was performed during
      the last 10 years in 93 males of whom 79 had classic bladder exstrophy and 14 had
      complete epispadias. Primary repair was performed in 65 boys with classic bladder
      exstrophy and 12 with epispadias, and secondary repair was done after prior
      failed reconstruction in 14 boys with classic exstrophy and 2 with complete
      epispadias. RESULTS: At mean followup of 68 months 87 patients had a horizontal
      or downward angled penis while standing. The incidence of urethrocutaneous
      fistulas was 23% in the immediate postoperative period and 19% at 3 months. A
      urethral stricture at the proximal anastomotic area developed in 7 patients and 5
      (4 with exstrophy and 1 with epispadias) had minor skin separations of the dorsal
      penile skin closure. Catheterization or cystoscopy in 77 cases revealed an easily
      negotiable neourethral channel. CONCLUSIONS: The modified Cantwell-Ransley
      epispadias repair produces an excellent functional and cosmetic result.

PMID- 10958737
TI  - How well do patients with exstrophy actually void?
AB  - PURPOSE: Achieving continence and preserving renal function are goals in the care
      of patients with bladder exstrophy. The Young-Dees-Leadbetter bladder neck
      reconstruction should ideally provide continence and normal voiding dynamics
      without the need for intermittent catheterization. We review our experience with
      bladder neck reconstruction in this population with emphasis on voiding dynamics
      among those patients doing well. MATERIALS AND METHODS: We retrospectively
      analyzed all patients with the exstrophy-epispadias complex seen at our
      institutions since 1985. We reviewed staged reconstruction in 53 patients,
      including 31 with classic bladder exstrophy, 4 with exstrophy variants and 18
      with incontinent epispadias. Patients with additional neurogenic dysfunction were
      excluded from study. Subjective and objective data regarding voiding function and
      complications were collected. RESULTS: Complete reconstruction for continence was
      performed in 38 cases, of which 11 that required bladder augmentation with
      bladder neck reconstruction or who had a different primary continence procedure
      were excluded from study. The remaining 27 patients treated with the Young-Dees
      Leadbetter bladder neck reconstruction had 2 or more years of followup (mean
      5.9). Dry intervals of at least 2 hours were achieved by 18 patients and all were
      considered by parents to void well. Despite near or total subjective continence
      and "good" voiding, 13 of these 18 patients (72%) have clinical problems related
      to emptying, which include recurrent urinary tract infections in 10, epididymitis
      in 2 and bladder calculi in 4. Objective urodynamic parameters confirm poor
      voiding in most patients. CONCLUSIONS: Bladder neck reconstruction in patients
      with exstrophy can achieve continence without intermittent catheterization. In
      our experience patients who achieve these goals have an alarming frequency of
      clinical and urodynamic problems related to emptying. One must question the
      normalcy of the voiding pattern and price to achieve continence among patients
      with exstrophy.

PMID- 10958738
TI  - Uroplakin and androgen receptor expression in the human fetal genital tract:
      insights into the development of the vagina.
AB  - PURPOSE: Although a dual origin of the vagina has been popularized, other
      theories support a mullerian or wolffian duct origin or various combinations of
      these structures and the urogenital sinus. Uroplakins are specialized membrane
      proteins of the urothelial plaque, constituting the asymmetrical unit membrane of
      the bladder, and represent specific molecular markers of urothelial
      differentiation. We hypothesize that the epithelium of the dorsal wall of the
      urogenital sinus is involved in the formation of the sinovaginal bulbs and will
      express uroplakins. In addition, localization of the androgen receptor and its
      temporal expression during development may in part explain the varied effects of
      androgens on the lower female genital tract in congenital adrenal hyperplasia.
      MATERIALS AND METHODS: Lower genitourinary tracts from 4 human female fetuses (9
      to 18 weeks) were serially sagittally sectioned. Representative sections were
      stained with hematoxylin and eosin, rabbit antibodies against panuroplakin and
      antibodies to the androgen receptor. RESULTS: At 9 weeks of gestation the
      urogenital sinus showed evidence of evagination and the formation of the
      sinovaginal bulbs. The urothelium of the entire urogenital sinus expressed
      uroplakins including the region of the dorsal wall involved in evagination and
      formation of the sinovaginal bulbs. The mullerian ducts were in direct contact
      with the area of urogenital sinus evagination but were not in continuity with the
      sinus. Androgen receptors were expressed in the epithelium and the stroma of the
      urogenital sinus, sinovaginal bulbs, and mullerian and wolffian ducts. By 14
      weeks androgen receptor expression was almost absent in the urothelium of the
      urogenital sinus, and the epithelium and surrounding stroma of the lower vagina
      and mullerian ducts. CONCLUSIONS: The area of evagination of the urogenital sinus
      expresses uroplakins, is involved in the formation of the sinovaginal bulbs and
      further substantiates the urogenital sinus origin of the lower vagina. Since
      testosterone inhibits formation of the lower vagina, the timing of exposure to
      systemic testosterone in congenital adrenal hyperplasia will determine the
      phenotypic appearance of the external genitalia and effect of testosterone on the
      development of the lower genital tract. If exposure to testosterone occurs after
      12 weeks only clitoromegaly occurs. Androgen receptor is absent in the urogenital
      sinus urothelium, vaginal epithelium and mullerian ducts by 14 weeks, suggesting
      that these tissues become androgen insensitive and vaginal development will
      proceed normally after that critical time.

PMID- 10958739
TI  - Consensus on the prenatal management of antenatally detected urological
      abnormalities.
AB  - PURPOSE: The incidence of an antenatally detected genitourinary abnormality is
      0.5% of all pregnancies assessed, and rarely is antenatal intervention indicated.
      A survey of pediatric urologists was undertaken to evaluate current practice
      patterns and recommendations regarding the need to intervene in the antenatal
      period. MATERIALS AND METHODS: A survey instrument was mailed to all members of
      the Society for Fetal Urology. There were 7 case scenarios that addressed
      critical decision points in patients with antenatally detected genitourinary
      abnormalities. RESULTS: A total of 112 of 188 Society for Fetal Urology members
      (60%) completed the survey. Observation with serial ultrasound was recommended
      for a 32-week fetus with ureteropelvic junction obstruction. For a 36-week fetus
      with suspected posterior urethral valves without oligohydramnios most respondents
      elected no intervention with a minority favoring early delivery. For a 23-week
      fetus with suspected posterior urethral valves and oligohydramnios with normal
      bladder electrolytes most respondents agreed with a vesicoamniotic shunt. There
      was no clear consensus for a 20-week fetus with suspected posterior urethral
      valves, oligohydramnios and a nonfunctioning right kidney. Most respondents
      recommended serial ultrasound to follow an 18-week fetus with suspected posterior
      urethral valves and normal amniotic fluid. Antenatal intervention was not
      recommended for a 20-week fetus with bilateral renal cystic disease, and most
      respondents elected no intervention for a 28-week fetus with a solitary kidney
      with suspected ureteropelvic junction obstruction and normal amniotic fluid.
      CONCLUSIONS: Situations that warrant antenatal intervention for a genitourinary
      abnormality are exceedingly low and may include cases of oligohydramnios,
      suspected favorable renal function and the absence of life threatening congenital
      abnormalities. In cases with normal amniotic fluid antenatal intervention is not
      recommended regardless of the detected abnormality. There is an emerging trend
      toward early delivery of fetuses with severe genitourinary abnormalities, normal
      amniotic fluid and confirmed lung maturity.

PMID- 10958741
TI  - Is primary obstructive megaureter repair at risk for contralateral reflux?
AB  - PURPOSE: Contralateral vesicoureteral reflux occurs after successful unilateral
      reflux repair in a significant proportion of patients without correlation to the
      surgical approach. Unilateral congenital obstructive megaureter was compared to
      primary vesicoureteral reflux with regard to the risk of onset of contralateral
      reflux after unilateral ureteral reimplantation. MATERIALS AND METHODS:
      Unilateral congenital obstructive megaureter was diagnosed in 58 consecutive
      patients 2 to 10 years old (mean age 3.2). Cross-trigonal ureteroneocystostomy
      was performed in 57 cases and longitudinal ureteral reimplantation, according to
      the Politano-Leadbetter technique was done in 1. Longitudinal tapering according
      to Hendren was performed in 44 ureters, and the Kalicinski folding was used to
      repair 11 ureters. All patients underwent serial renal ultrasound,
      diethylenetetraminepentaacetic acid nuclear scan, excretory urogram and voiding
      cystourethrogram. The control group was composed of 98 age matched children with
      unilateral vesicoureteral reflux who underwent unilateral reimplantation with or
      without tapering. Fisher's exact test and Student's t test were used for
      statistical analysis. RESULTS: Followup ranged from 1 to 5 years. All patients in
      both groups underwent a voiding cystourethrogram at 6 months, and renal
      ultrasound at 3, 6 and 12 months postoperatively. Grade 2 reflux developed in 1
      study group patient after contralateral Kalicinski ureteral folding and cross
      trigonal reimplantation (1.7%). In the control group new onset contralateral
      reflux developed in 11 cases (11.2%). The difference was statistically
      significant (p <0.005, Fisher's exact test p = 0. 033). CONCLUSIONS: Ureteral
      reimplantation for unilateral congenital obstructive megaureter is not correlated
      with the development of contralateral reflux. The occurrence of contralateral
      reflux after successful unilateral reflux repair is high (11.2%), and is not
      correlated with age, sex and technique of reimplantation or tapering. These
      results support the hypothesis that the functional anatomy of the trigone is
      preserved in congenital obstructive megaureter but is impaired on both sides in
      cases of unilateral vesicoureteral reflux. The surgical management of unilateral
      primary vesicoureteral reflux and congenital obstructive megaureter should be
      differentiated based on these results.

PMID- 10958740
TI  - The natural history of neonatal vesicoureteral reflux associated with antenatal
      hydronephrosis.
AB  - PURPOSE: In an attempt to evaluate the natural history of neonatal vesicoureteral
      reflux, patients with antenatal history of hydronephrosis and documented reflux
      in the first 30 days of life were analyzed. MATERIALS AND METHODS: Between 1993
      and 1998, 260 patients with a history of antenatal hydronephrosis were referred
      for evaluation. Of these patients 31 were diagnosed with unilateral or bilateral
      refluxing renal units (54 renal units). Patients were treated with a prospective
      plan of observational therapy and prophylactic antibiotics, and resolution rate
      was calculated in patients with adequate followup. Reflux grade was correlated
      with postnatal ultrasonographic findings, urinary tract infections and
      differential renal function. Outcome analysis of 34 high grade (III to V)
      refluxing renal units using the Kaplan-Meier survival curves was undertaken with
      the end point being complete resolution or improvement. Three patients with
      vesicostomy and 2 who underwent ureteral reimplantation were excluded from
      analysis. RESULTS: Reflux was grade I in 5% (33% males), II in 15% (62% males),
      III in 32% (71% males), IV in 18% (90% males) and V in 30% (100% males) of the
      patients. Postnatal ultrasound findings correlated poorly with the presence and
      degree of vesicoureteral reflux. Of 17 patients followed for at least 14 months
      (average followup 20) there was complete resolution in 60% with grade III, 50%
      with grade IV and 28% with grade V reflux. Using the Kaplan-Meier estimate there
      was a 50% chance of improvement (decrease in reflux grade by at least 2 grades)
      in high grade reflux by age 16 months. Urinary tract infections developed in 8
      patients (26%) while on antibiotics. Of 46 renal units in 23 patients evaluated
      with a renal scan before urinary tract infection, 12 had less than 35% function.
      CONCLUSIONS: A normal postnatal ultrasound should not be a basis for excluding
      the use of cystography. Our Kaplan-Meier estimate shows that high grade reflux
      does improve and may resolve spontaneously. In addition, renal scarring may be
      seen with high and low grade reflux in the absence of urinary tract infection but
      high grade reflux is associated with a higher incidence of infection.

PMID- 10958742
TI  - The prevalence of persistent vesicoureteral reflux after 1 negative nuclear
      medicine cystogram.
AB  - PURPOSE: Radionuclide cystography is a widely used test for the diagnosis or
      indication of resolution of vesicoureteral reflux. The recurrence or persistence
      of reflux after 1 negative radionuclide cystogram has been previously reported.
      We examined the value of a second radionuclide cystogram in patients who were
      believed to be cured on 1 previous study and tried to identify variables that
      could explain the false-negative result on the initial cystogram. MATERIALS AND
      METHODS: The study included 85 patients with primary vesicoureteral reflux,
      treated conservatively between 1991 and 1996 who had 1 negative radionuclide
      cystogram. A repeat radionuclide cystogram was done 12 to 18 months after the
      negative study. Patients were divided into those with and without reflux
      recurrence identified, and compared in regard to sex distribution, age at
      presentation and reflux resolution, time between presentation and first negative
      radionuclide cystogram, change in reflux grade between presentation and just
      before resolution, side of reflux at presentation and grade before resolution.
      The differences between both groups were statistically analyzed. RESULTS: Of the
      85 patients 25 (29%) had reflux recurrence, including 18 (72%) with grade 2 or
      greater recurrent reflux and 15 (60%) with persistent reflux 12 months after the
      second positive radionuclide cystogram. There was no observed association between
      the 2 groups in any of the variables (p >0.05). CONCLUSIONS: This study
      emphasizes the importance of a second negative radionuclide cystogram to indicate
      the absence or resolution of reflux as 1 negative cystogram alone would have
      missed persistent reflux in 25 of 85 patients at 1 year and 15 of 85 patients at
      2. Whether absence or resolution of reflux is a variable of the disease or an
      unknown factor inherent in the test is unknown as there was no statistical
      difference in the parameters studied between our 2 groups.

PMID- 10958743
TI  - A bioassay evaluation of the urinary antibacterial efficacy of low dose
      prophylactic antibiotics in children with vesicoureteral reflux.
AB  - PURPOSE: We evaluated by means of a bioassay the efficacy of 4 different
      antibiotics administered in a prophylactic dose to children with vesicoureteral
      reflux. MATERIALS AND METHODS: A total of 159 urine samples from 53 children
      taking prophylactic antibiotics with proved vesicoureteral reflux were tested.
      The children were divided into 4 groups according to the antibiotic given, which
      included nalidixic acid, cephalexin, cotrimoxazole and cefixime. Urine samples
      were collected in the morning, at noon and in the evening, and each sample was
      bioassayed for growth inhibition of a standard Escherichia coli. The urine volume
      used was specifically determined for each antibiotic, and growth inhibition by
      this specific volume was equivalent to that produced by standard diffusion disks.
      In addition, the specific gravity, which reflected urinary concentration of each
      sample, was measured. RESULTS: Mean patient age plus or minus standard deviation
      of the 4 groups was 53 +/- 41 for nalidixic acid, 23 +/- 34 for cephalexin, 55 +/
      35 for cotrimoxazole and 47 +/- 35 months for cefixime, respectively. In
      children less than 2 years old specific gravity was higher in the morning (1.021
      +/- 0.0006 versus 1.0008 +/- 0.0004 at 8 a.m. and 2 p. m., respectively, p
      <0.05). In contrast, in children older than 4 years the specific gravity was
      higher in the afternoon and evening hours (1.019 +/- 0.003 versus 1.007 +/- 0.003
      at 2 p.m. and 8 a.m., respectively, p <0.05). The percentage of patients who
      demonstrated growth inhibition in all 3 samples of the test day was 7%, 6%, 69%
      and 44% for nalidixic acid, cephalexin, cotrimoxazole and cefixime, respectively
      (p <0.001 for cotrimoxazole and cefixime versus nalidixic acid and cephalexin.
      Divided into morning, noon and evening, the percentage of samples that
      demonstrated growth inhibition was 85.7%, 21.4% and 7.1% for nalidixic acid,
      37.5%, 12. 5% and 6.3% for cephalexin, 100%, 92.3% and 76.9% for cotrimoxazole
      and 100%, 77.7% and 55.5% for cefixime, respectively. A direct correlation was
      found between specific gravity and growth inhibition (r = 0.55, p <0.001).
      CONCLUSIONS: Urine concentration during the day is dependent on age with older
      children having more concentrated urine in the latter part of the day. Growth
      inhibition is enhanced by concentrated urine. Compared to nalidixic acid and
      cephalexin, cotrimoxazole and cefixime produce a sustained bactericidal effect
      for about 60% of a 24-hour day due to the longer half-life.

PMID- 10958744
TI  - Oral cimetidine for the management of genital and perigenital warts in children.
AB  - PURPOSE: It is believed that most warts are self-limiting and generally require
      little or no treatment. When numerous or almost complete infestation of the
      perineum, genital area and groin is encountered it can be distressing and a
      difficult problem to treat in children. Multiple treatments with caustic agents
      are sometimes necessary, and treatment of perigenital warts may require use of
      anesthesia for multiple procedures. Cimetidine is a histamine receptor antagonist
      that has been used mainly to treat peptic ulcer disease. Recently it has been
      reported to be useful for the treatment of mucocutaneous candidiasis, herpes
      simplex, herpes zoster and verruca because of its immunomodulatory effects.
      Several studies have been published indicating its effectiveness in the treatment
      of warts. MATERIALS AND METHODS: We treated 4 children with extensive condylomata
      acuminata of the genital and perigenital areas with high doses of cimetidine in
      an attempt to eradicate the condyloma and avoid recurrence in 2 and as primary
      treatment in 2. All patients were treated with 30 to 40 mg./kg. cimetidine daily
      in 3 divided doses during a 3-month period. RESULTS: All patients are free of
      condyloma at 24 months following treatment. CONCLUSIONS: Our results show that
      cimetidine is useful for primary and adjunctive treatment of condyloma in young
      children. It also appears to be effective as first line therapy.

PMID- 10958745
TI  - Laparoscopic retroperitoneal nephrectomy in high risk children.
AB  - PURPOSE: Nephrectomy may be indicated in children with end stage renal disease
      before transplantation. We studied the feasibility and results of nephrectomy
      performed via a retroperitoneal laparoscopic approach in these high risk
      children. MATERIALS AND METHODS: We performed 12 nephrectomies in 9 children with
      end stage renal disease and a mean age of 7 years (range 7 months to 13 years)
      through a 3 trocar retroperitoneal laparoscopic approach. Cases were classified
      as American Society of Anesthesiologists grade III and presented with end stage
      renal disease, hypertension, thrombocytopenia and/or the nephrotic syndrome. The
      renal artery and vein were ligated separately with endocorporeal knots and clips.
      Mean size of the kidney was 8 cm. (range 5 to 12). Bilateral nephrectomy was
      performed simultaneously in 2 patients 7 and 12 months old, respectively.
      Cardiorespiratory changes related to retroperitoneal gas insufflation were
      assessed prospectively. To compare laparoscopic versus open nephrectomy we
      retrospectively analyzed the data of 12 open nephrectomies performed in 9
      children with similar nephrological indications. RESULTS: The procedure was
      feasible in all cases without conversion to open surgery, and no intraoperative
      incident occurred. Mean operative time of laparoscopic nephrectomy was 2 hours
      (range 1 hour 20 minutes to 3 hours 10 minutes). After retroperitoneal carbon
      dioxide insufflation systolic arterial pressure and end-tidal carbon dioxide were
      significantly increased without the need for specific measure to correct these
      modifications. Hemodialysis began 1 day postoperatively and feeding began 2 days
      postoperatively. Mean hospital stay was 5.2 days (range 3 to 7). The comparative
      study of the open nephrectomy group showed no significant difference in mean
      operating time (p = 0.07), and hospital stay was significantly shorter for the
      laparoscopic group (p <0.001). CONCLUSIONS: Retroperitoneal laparoscopic
      nephrectomy is safe and feasible for high risk children. The relatively long
      operating time is necessary for hemostasis in these children at risk for
      hemorrhagic complications.

PMID- 10958746
TI  - Retroperitoneal laparoscopy for renal biopsy in children.
AB  - PURPOSE: We report our experience with the retroperitoneal laparoscopic approach
      for treating pediatric patients and when the percutaneous needle approach is not
      possible due to uncontrolled hypertension, bleeding disorders, anti-clotting
      medications and anatomical abnormalities. MATERIALS AND METHODS: Retroperitoneal
      laparoscopic renal biopsy was performed in 20 patients 2 to 18 years old (mean
      age 9.7) during a 16-month period. At the same time 53 percutaneous needle
      biopsies and 1 open biopsy were performed. The child is in a flank position, and
      2 trocars are used via a direct vision approach. The first trocar is 12 mm. in
      diameter and positioned on the posterior axillary line, and the second trocar is
      5 mm. in diameter and is entered 4 cm. anteriorly. Gentle dissection is done to
      free the lower pole of the selected kidney, biopsy forceps are used to grasp the
      specimen under direct vision and the biopsy site is fulgurated using bipolar
      electrocautery. RESULTS: Biopsy was performed successfully in all cases except 1,
      which was converted to an open procedure. Mean operative time was 40 minutes,
      blood loss was minimal and mean hospital stay was 1.2 days postoperatively. No
      pain medication was required postoperatively, and all patients returned to their
      usual activities within 3 to 5 days. A minor intraoperative complication, which
      was a peritoneal tear with no postoperative sequelae, occurred in 1 case.
      CONCLUSIONS: The retroperitoneal laparoscopic technique is simple and safe, and
      does not require extensive laparoscopic experience. We believe that this approach
      is reliable, and has less morbidity and several advantages compared to open
      surgery. It should be selected as the first choice for treating pediatric
      patients when percutaneous needle renal biopsy is contraindicated.

PMID- 10958748
TI  - Robert d. jeffs

PMID- 10958747
TI  - Laparoscopic antegrade continence enema in situ appendix procedure for refractory
      constipation and overflow fecal incontinence in children with spina bifida.
AB  - PURPOSE: The antegrade continence enema procedure allows patients with neurogenic
      bowel to administer large volume enemas through a right lower quadrant stoma to
      flush the colon every other day. This procedure results in freedom from
      refractory constipation and diapers required by unexpected episodes of overflow
      fecal incontinence. We present a simplified laparoscopic technique using in situ
      appendix. MATERIALS AND METHODS: A total of 6 male and 10 female children with a
      mean age of 12 years (range 4 to 21) and neurogenic bowel secondary to
      myelomeningocele underwent the antegrade continence enema in situ appendix
      procedure. The procedure was done with laparoscopic assistance, and associated
      with other bladder and bladder outlet reconstructive surgery in 5 patients. In 3
      patients, a purely laparoscopic antegrade continence enema in situ appendix
      procedure was performed. The appendix and cecum were mobilized, and the tip of
      the appendix was anastomosed directly to the skin of the right lower quadrant
      through 1 of the 5 mm. lower quadrant port sites. The continence mechanism is
      simply a function of the appendix length and the mucosal coaptation of the
      appendiceal lumen. A 6Fr silicone Foley catheter is used to stent the
      mucocutaneous anastomosis. Concomitant procedures included ileocystoplasty,
      ileovesicostomy, sigmoidovesicostomy or ureterovesicostomy, and/or pubovaginal
      sling done through a low Pfannenstiel incision after laparoscopic mobilization of
      the appendix and cecum. RESULTS: The 3 patients treated with the laparoscopic
      antegrade continence enema procedure ate the day of surgery and were discharged
      home the next morning. Constipation and fecal incontinence resolved in all cases.
      All antegrade continence enema stomas were catheterized easily with a 6 or 8Fr
      feeding tube and were continent. Complications in the 8 laparoscopic and
      laparoscopic assisted cases included stomal stenosis requiring dilation in the
      office and obstructive volvulus associated with malrotation requiring segmental
      resection. Patient mothers in particular were gratified by this procedure at a
      mean followup of 11/2 years. CONCLUSIONS: The simplified antegrade continence
      enema in situ appendix procedure works well for refractory constipation and
      overflow fecal incontinence in children with neurogenic bowel secondary to spina
      bifida. Coaptation of the appendiceal lumen and use of small catheters allow for
      persistent continence without a formal surgically constructed valve mechanism.
      The combined antegrade continence enema and either ileovesicostomy or
      sigmoidovesicostomy continent urinary diversion procedures allow children to
      control bowel and bladder evacuation programs. A laparoscopic approach is
      reasonable particularly in cases requiring no other procedures.

PMID- 10958749
TI  - Treatment of distal ureteral stones in children: similarities to the american
      urological association guidelines in adults.
AB  - PURPOSE: The American Urological Association (AUA) published clinical guidelines
      for the treatment of ureteral calculi in adults and note that up to 98% of stones
      less than 5 mm. in diameter will pass spontaneously. Ureteroscopy and shock wave
      lithotripsy were acceptable treatment choices for stones less than 10 mm. in
      diameter in the distal ureter. We reviewed our management of distal ureteral
      stones in children to see if the AUA Guidelines for adults would apply. MATERIALS
      AND METHODS: A total of 14 males and 19 females with a mean age of 12 years
      (range 0.5 to 17) required hospitalization in the last 6 years for distal
      ureteral obstruction due to stones. Excretory urography or computerized
      tomography was performed in all cases, and mean stone size was 4 mm. (range 1 to
      15). When stones did not pass spontaneously most patients were treated with
      ureteroscopic laser lithotripsy. RESULTS: There were 12 (36%) with a mean age of
      11 years and a mean stone size of 2 mm. (range 1 to 3) who passed stones
      spontaneously with intravenous hydration and narcotics. No child passed a stone 4
      mm. or greater spontaneously in this series. Of 21 patients (64%) with a mean age
      of 12 years and a mean stone size of 5 mm. (range 1 to 15) 2 were treated with
      ureteral stents, 17 with ureteroscopic lithotripsy and 2 with shock wave
      lithotripsy. All patients were stone-free at the end of the procedures. The stone
      composition was predominantly calcium oxalate. Mean followup was 2 years.
      CONCLUSIONS: Similar to the AUA guidelines in adults, most stones less than 3 mm.
      in diameter in the distal ureter of children will pass spontaneously. Stones 4 mm
      or greater in the distal ureter are likely to require endosurgical treatment.
      Ureteroscopy and shock wave lithrotripsy have a high success rate for stones
      between 4 and 15 mm. in the distal ureter. Needle ureteroscope and laser
      lithotripsy have allowed more stones to be treated safely and effectively in
      smaller children.

PMID- 10958750
TI  - Hypercalciuria and pediatric stone recurrences with and without structural
      abnormalities.
AB  - PURPOSE: This study defines to what extent hypercalciuria represents a risk
      factor for recurrent calcium oxalate or nonstruvite stones. Long-term followup of
      children with hypercalciuria after an initial stone episode allowed us to
      determine the rate of stone recurrence. MATERIALS AND METHODS: A total of 44
      pediatric patients with stones were diagnosed with hypercalciuria, including 7
      with structural abnormalities and 37 with normal anatomy. Of these patients 27
      had adequate long-term followup. RESULTS: There were 9 stone recurrences in the
      27 patients who were evaluated long term for an overall recurrence rate of 33%.
      Recurrences developed 3 to 15 years after the initial episode (average time to
      recurrence 7.2 years), and none of the patients with structural abnormalities had
      hydronephrosis at recurrence. Of the 9 patients with stone recurrences 3 were
      female and 6 were male, and 4 had multiple stone recurrence episodes. Of these 9
      cases of recurrent stones 8 had a positive family history for stone disease in a
      first degree relative, whereas only 8 of 18 cases without stone recurrence had a
      positive family history (p = 0. 04). CONCLUSIONS: Hypercalciuria is a risk factor
      for recurrence in the pediatric patient with stones with and without structural
      abnormalities. New stones can occur several years after the initial episode and
      can extend through postpuberty.

PMID- 10958751
TI  - Long-term followup of endoscopic incision of ureteroceles: intravesical versus
      extravesical.
AB  - PURPOSE: Endoscopic incision was performed as the initial therapy for
      ureteroceles in children presenting to our institutions between 1985 and 1990. To
      assess the long-term efficacy of this treatment modality we reevaluated the
      outcome of these patients. MATERIALS AND METHODS: Parameters reviewed included
      patient age at surgery, position of the ureterocele, a duplex system,
      preoperative and postoperative reflux, and the need for additional operations.
      Statistical analysis consisted of chi-square and Wilcoxon's rank sum tests.
      RESULTS: Of the patients 22 had intravesical and 22 had extravesical
      ureteroceles. Average age at initial surgery was 1.9 +/- 3.7 years with average
      followup of 7.2 +/- 3.1 years. A second operation was required in 18 cases (41%),
      which was significantly more likely for an extravesical ureterocele (18% versus
      64%, p = 0. 002), a duplex system (p = 0.026) or preoperative reflux (p = 0.02).
      Second operations included reimplantation in 13 cases, upper pole partial
      nephrectomy in 7, total nephroureterectomy in 3, bladder neck reconstruction in 3
      and lower pole pyeloplasty in 3. The only secondary operations performed for
      intravesical ureteroceles were reimplantation in 3 cases and upper pole
      nephrectomy in 1. New onset reflux developed in 14 of 27 patients (52%)
      postoperatively, including 7 with intravesical and 7 with extravesical
      ureteroceles. None required a second open operation. CONCLUSIONS: With extended
      followup the percentage of patients requiring open surgery after endoscopic
      incision of ureteroceles increased from our original report of 27% to 41% (p =
      0.166). Only 18% of cases with an intravesical ureterocele required a subsequent
      operation compared to 64% with an extravesical ureterocele (p = 0.002). The
      reduction in size of the obstructed ureter following endoscopic decompression
      facilitated successful reimplantation. Endoscopic puncture permits definitive
      treatment in the majority of children by at most a single incision, open
      operation at the bladder level.

PMID- 10958752
TI  - The long-term followup of newborns with severe unilateral hydronephrosis
      initially treated nonoperatively.
AB  - PURPOSE: During the last decade it has become apparent that prenatally detected,
      unilateral severe hydronephrosis does not necessarily represent obstruction and
      may spontaneously improve or resolve postnatally. To define its natural history
      better we performed a long-term (mean 78 months) followup study of infants with
      hydronephrosis. MATERIALS AND METHODS: A total of 104 newborns with antenatally
      diagnosed, primary, unilateral severe hydronephrosis were followed nonoperatively
      unless evidence of renal deterioration occurred for which pyeloplasty was
      performed. RESULTS: All 23 infants (22%) who required pyeloplasty were younger
      than 18 months and had progressive hydronephrosis and/or reduction in
      differential renal function. Differential function exceeded predeterioration
      levels in all kidneys postoperatively. Of those cases followed nonoperatively
      hydronephrosis resolved in 69% and improved in 31%. Mean time to maximum
      improvement of hydronephrosis was 2.5 years. In 76% of those cases followed
      nonoperatively initial differential function was greater than 40% and final
      function averaged 49%. In the remaining 24% of cases differential function was
      less than 40% (mean 23%), and in an average of 18 months differential function
      increased to a mean of 47%. Initial half-time in nonoperative cases was greater
      than 30 minutes in 37%, 20 to 30 in 21% and less than 20 in 42%. Final half-time
      was greater than 30 minutes in 16%, 20 to 30 in 17% and less than 20 in 67%. Half
      time was greater than 30 minutes in 87% of the patients and 20 to 30 in 4%
      before, and greater than 30 in 10%, 20 to 30 in 27% and less than 20 in 63% after
      pyeloplasty. CONCLUSIONS: Unilateral newborn hydronephrosis appears to be
      relatively benign and in most instances dilatation and renal function improve
      with time. However, close followup is necessary to identify the subgroup of less
      than 25% of infants with obstruction because prompt pyeloplasty will prevent
      permanent loss of renal function. Standard tests for assessing obstruction in
      older patients appear to be invalid in infants because prolonged half-time and/or
      high grade hydronephrosis is neither an indicator of obstruction or surgery.
      Nonoperative treatment with close followup especially during the first 2 years is
      safe and recommended for these children.

PMID- 10958753
TI  - Lessons learned from laser tissue soldering and fibrin glue pyeloplasty in an in
      vivo porcine model.
AB  - PURPOSE: We compared sutured pyeloplasty to 2 newer techniques of tissue
      anastomosis, including laser soldered pyeloplasty using a diode laser with 50%
      albumin solder mixed with indocyanine green and fibrin glue. MATERIALS AND
      METHODS: We performed 53 pyeloplasties in 50 pigs using suture, laser or fibrin
      glue. In the immediate group anastomotic leak pressure was measured immediately
      postoperatively, and then animals were euthanized. At 1, 3 and 4 weeks
      postoperatively a pressure flow study at 10 cc per minute in cm. H2O was
      performed, and tissue was sent for histological and collagen content analysis.
      RESULTS: In the immediate studies laser soldering achieved a significantly higher
      mean anastomotic leak pressure (50.5 +/- 15.1 cm. H2O) than sutured (17.3 +/-
      5.4) or fibrin glued (3.5 +/- 1.5) repairs. In the 1, 2 and 4-week studies
      animals in the sutured pyeloplasty group had no complications, and all pressure
      flow studies except 1 were normal. However, in the laser soldered groups we
      observed 8 urinomas in 19 animals, and most occurred during the first part of our
      study. This complication was prevented by stopping urine flow at the anastomotic
      site at laser irradiation and by improving application of the solder. Of the 11
      animals in which pressure flow studies were performed only 2 were obstructed. Of
      the 7 chronic fibrin glue group 4 animals had urinomas and 2 had unobstructed
      pressure flow studies. Histological studies and immunohistochemical staining for
      collagen showed no differences in collagen distribution among the 3 procedures.
      CONCLUSIONS: Laser soldering and fibrin glue pyeloplasties are not superior in
      the long-term compared to sutured pyeloplasty. Fibrin glue in our animal model
      had the highest failure rate. Further improvements in the technical aspect of
      laser tissue welding need to be made to benefit from its theoretical advantages
      in minimally invasive surgery.

PMID- 10958754
TI  - Comparative assessment of pediatric testicular volume: orchidometer versus
      ultrasound.
AB  - PURPOSE: Testicular volume measurements obtained with the Prader and Rochester
      orchidometers were compared to those obtained using scrotal ultrasound. The
      ability of each orchidometer versus ultrasound in detecting volume differential
      between 2 testes and the accuracy of orchidometer measurement by a less
      experienced examiner to that of a urologist were compared. MATERIALS AND METHODS:
      A total of 65 males were examined by the attending urologist and urology nurse
      using the Prader and Rochester orchidometers, and scrotal ultrasound was
      subsequently performed by an attending radiologist. Statistical analysis of the
      results was performed to determine the correlation of orchidometer measurements
      between examiners, as well as with ultrasound, and sensitivity and specificity of
      orchidometer and ultrasound in detecting defined volume differentials between
      testes of 10%, 15%, 20% and 25%. RESULTS: There was a strong linear relationship
      between testicular volume measurements using either orchidometer and ultrasound.
      To detect a defined volume differential as determined by ultrasound orchidometer
      sensitivity was weak, whereas orchidometer specificity was better. There was a
      strong correlation between orchidometer measurements of the urology nurse and
      attending urologist. CONCLUSIONS: Although the orchidometer remains valuable in
      assessing size of the individual testis, it is too insensitive to volume
      differentials relative to ultrasound to be used routinely to determine growth
      impairment. For this reason observation of an adolescent with varicocele should
      include an annual ultrasound assessment of testicular volume.

PMID- 10958755
TI  - Testicular health awareness in pubertal males.
AB  - PURPOSE: We examined the knowledge and understanding of male teenagers of the
      necessity for genital examination, and signs and symptoms of serious testicular
      pathology. Furthermore, current national guidelines for health education were
      reviewed to understand better the curriculum used by the educational system and
      to assess its effectiveness. MATERIALS AND METHODS: In 1998, a 5-question survey
      was administered privately and confidentially to male athletes before a sports
      physical examination. The athletes were 12 to 18 years old, attended middle or
      high school, and were sampled randomly. The National Health Education Standards
      benchmark for grades 9 through 11 was examined with specific attention to male
      self-health education standards. RESULTS: A total of 318 athletes responded
      revealing that 54% did not know why the genitals were examined on a sports
      physical examination, 45% did not use appropriate testicular protection and the
      majority did not respond appropriately to symptoms of serious testicular
      pathology. Despite the fact that 46% of respondents answered that checking for a
      hernia is reason for a genital examination there was no mention of tumor,
      infection or varicocele. Review of the benchmarks revealed no standards referring
      to a minimum understanding of anatomy or physiology. Generalized guidelines for
      high risk behaviors were provided without specific mention of testicular torsion,
      cancer, varicocele or sexually transmitted diseases. CONCLUSIONS: Young males are
      at higher risk for testicular torsion, cancer and varicocele than other age
      groups, and yet our population was universally unaware of these as a reason for
      genital examination. Furthermore, the majority did not respond appropriately to
      questions regarding serious testicular pathology. Review of national guidelines
      reveals poorly defined, nonspecific provisions for male self-health care.
      Therefore, we have developed a curriculum for male self-health to address this
      problem.

PMID- 10958756
TI  - Decreased linear growth associated with intestinal bladder augmentation in
      children with bladder exstrophy.
AB  - PURPOSE: We determine if enterocystoplasty results in delayed linear growth using
      a case controlled study to observe the effects of intestinal bladder augmentation
      on growth in patients with bladder exstrophy. MATERIALS AND METHODS: A total of
      50 patients who had undergone bladder augmentation for incontinence due to
      classic bladder exstrophy were selected from our patient database and matched for
      gender, age and type of exstrophy with 50 patients who had nonaugmented bladder
      exstrophy. Patients were then contacted and asked to permit the pediatricians to
      release growth charts. Once consent was obtained the charts were requested from
      the pediatricians, and evaluable data, defined as at least 1 height before and
      after augmentation, were obtained for 17 of 50 (34%) augmented and 15 of 50 (30%)
      nonaugmented cases. RESULTS: Mean age at surgery was 7.7 years. Delayed growth as
      defined by a postoperative decrease in percentile height occurred in 14 of 17
      (82%) augmented cases (mean loss 15.6 percentile points). Delayed growth after
      age 7.7 years occurred in 5 of 15 (33%) controls but average growth for the
      entire group was 6.7 percentile points (p = 0. 014). Mean followup was 5.7 years
      (median 4.9) for the augmented group and 7.3 years (median 8.2) for the control
      group. CONCLUSIONS: Intestinal bladder augmentation is associated with a nearly
      universal decrease in percentile height. Close long-term followup of these
      patients and analysis of subtle metabolic alterations may provide information to
      help minimize or prevent growth impediment in the future.

PMID- 10958757
TI  - Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene
      in GK rats.
AB  - Genetic analysis of the diabetic GK rat has revealed several diabetes
      susceptibility loci. Congenic strains have been established for the major
      diabetes locus, Niddm1, by transfer of GK alleles onto the genome of the
      normoglycemic F344 rat. Niddm1 was dissected into two subloci, physically
      separated in the congenic strains Niddm1b and Niddm1i, each with at least one
      disease susceptibility gene. Here we have mapped Niddm1b to 1 cM by genetic and
      pathophysiological characterization of new congenic substrains for the locus. The
      gene encoding insulin-degrading enzyme (IDE:) was located to this 1 cM region,
      and the two amino acid substitutions (H18R and A890V) identified in the GK allele
      reduced insulin-degrading activity by 31% in transfected cells. However, when the
      H18R and A890V variants were studied separately, no effects were observed,
      demonstrating a synergistic effect of the two variants on insulin degradation. No
      effect on insulin degradation was observed in cell lysates, indicating that the
      effect is coupled to receptor-mediated internalization of insulin. Congenic rats
      with the IDE: GK allele displayed post-prandial hyperglycemia, reduced
      lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake
      and reduced insulin degradation in isolated muscle. Analysis of additional rat
      strains demonstrated that the dysfunctional IDE: allele was unique to GK. These
      data point to an important role for IDE: in the diabetic phenotype in GK.

PMID- 10958758
TI  - Are postoperative studies justified after extravescial ureteral reimplantation?
AB  - PURPOSE: We evaluated the usefulness of postoperative imaging studies after
      extravesical ureteroneocystostomy and identified patient subsets in which these
      studies are necessary. MATERIALS AND METHODS: Records of 438 patients who had
      undergone extravesical ureteroneocystostomy from 1991 to 1997 were reviewed
      retrospectively. Study inclusion criterion was primary reflux with at least 1
      year of postoperative followup. Grades I to III reflux were defined as low, and
      grades IV and V were defined as high. All patients were on prophylactic
      antibiotics. Evaluation included ultrasound and a voiding cystourethrogram 3
      months postoperatively, and if reflux persisted the studies were repeated at 12
      months. RESULTS: A total of 438 patients (723 renal units) underwent extravesical
      ureteral reimplantation. At 3 months the procedure was successful in 93.2% of
      ureters (91.3% patients), and at 12 months the success rate increased to 97.9% of
      ureters (95.4% patients). There were 49 renal units in 38 cases that were
      refluxing at 3 months, 11 of which were contralateral. At 12 months reflux
      resolved spontaneously in 20 of 38 ipsilateral and 8 of 11 contralateral ureters.
      Of the remaining 18 ipsilateral units reflux was high grade preoperatively in 12
      and persisted postoperatively in 4. There was a statistically significant
      difference in the success rate at 1 year between high (94%) versus low (99%)
      grade reflux (p = 0.007). Age and preoperative bladder function did not
      significantly affect the success rates but males had a lower success rate.
      Hydronephrosis was noted in 7.2% of ureters at 6 weeks and in only 0.005% at 12
      months. CONCLUSIONS: Extravesical reimplantation is successful in treating
      vesicoureteral reflux. Postoperative voiding cystourethrogram should be reserved
      for high grade reflux. Limiting these studies will help reduce patient discomfort
      and the cost of treatment.

PMID- 10958759
TI  - Defective peroxisome membrane synthesis due to mutations in human PEX3 causes
      Zellweger syndrome, complementation group G.
AB  - Zellweger cerebro-hepato-renal syndrome is a severe congenital disorder
      associated with defective peroxisomal biogenesis. At least 23 PEX genes have been
      reported to be essential for peroxisome biogenesis in various species, indicating
      the complexity of peroxisomal assembly. Cells from patients with peroxisomal
      biogenesis disorders have previously been shown to segregate into >/=12
      complementation groups. Two patients assigned to complementation group G who had
      not been linked previously to a specific gene defect were confirmed as displaying
      a cellular phenotype characterized by a lack of even residual peroxisomal
      membrane structures. Here we demonstrate that this complementation group is
      associated with mutations in the PEX3 gene, encoding an integral peroxisomal
      membrane protein. Homozygous PEX3 mutations, each leading to C-terminal
      truncation of PEX3, were identified in the two patients, who both suffered from a
      severe Zellweger syndrome phenotype. One of the mutations involved a single
      nucleotide insertion in exon 7, whereas the other was a single-nucleotide
      substitution eight nucleotides from the normal splice site in the 3' acceptor
      site of intron 10. Expression of wild-type PEX3 in the mutant cell lines restored
      peroxisomal biogenesis, whereas transfection of mutated PEX3 cDNA did not. This
      confirmed that the causative gene had been identified. The observation of
      peroxisomal formation in the absence of morphologically recognizable peroxisomal
      membranes challenges the theory that peroxisomes arise exclusively by growth and
      division from preexisting peroxisomes and establishes PEX3 as a key factor in
      early human peroxisome synthesis.

PMID- 10958760
TI  - Multipoint genetic mapping with uniparental disomy data.
AB  - Uniparental disomy (UPD) refers to the presence of two copies of a chromosome
      from one parent and none from the other parent. In genetic studies of UPDs, many
      genetic markers are usually used to identify the stage of nondisjunction that
      leads to UPD and to uncover the associated unusual patterns of recombinations.
      However, genetic information in such data has not been fully utilized because of
      the limitations of the existing statistical methods for UPD data. In the present
      article, we develop a multilocus statistical approach that has the advantages of
      being able to simultaneously consider all genetic markers for all individuals in
      the same analysis and to allow general models for the crossover process to
      incorporate crossover interference. In particular, for a general crossover
      process model that assumes only that there exists in each interval at most one
      crossover, we describe how to use the expectation-maximization algorithm to
      examine the probability distribution of the recombination events underlying
      meioses leading to UPD. We can also use this flexible approach to create genetic
      maps based on UPD data and to inspect recombination differences between meioses
      exhibiting UPD and normal meioses. The proposed method has been implemented in a
      computer program, and we illustrate the proposed approach through its application
      to a set of UPD15 data.

PMID- 10958761
TI  - Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive
      cone-rod dystrophy.
AB  - The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4;
      previously denoted "ABCR") is mutated, in most patients, with autosomal recessive
      (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few
      cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been
      found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a
      cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany
      and The Netherlands with isolated CRD. Single-strand conformation-polymorphism
      analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients.
      In six patients, mutations were identified in both ABCA4 alleles; in seven
      patients, mutations were detected in one allele. One complex ABCA4 allele
      (L541P;A1038V) was found exclusively in German patients with CRD; one patient
      carried this complex allele homozygously, and five others were compound
      heterozygous. These findings suggest that mutations in the ABCA4 gene are the
      major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD,
      together with the gene's involvement in an as-yet-unknown proportion of cases
      with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the
      most frequent cause of inherited retinal dystrophy in humans.

PMID- 10958762
TI  - Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an
      examination of C677T and A1298C mutations.
AB  - Methylenetetrahydrofolate reductase (MTHFR) mutations are commonly associated
      with hyperhomocysteinemia, and, through their defects in homocysteine metabolism,
      they have been implicated as risk factors for neural tube defects and
      unexplained, recurrent embryo losses in early pregnancy. Folate sufficiency is
      thought to play an integral role in the phenotypic expression of MTHFR mutations.
      Samples of neonatal cord blood (n=119) and fetal tissue (n=161) were analyzed for
      MTHFR C677T and A1298C mutations to determine whether certain MTHFR genotype
      combinations were associated with decreased in utero viability. Mutation analysis
      revealed that all possible MTHFR genotype combinations were represented in the
      fetal group, demonstrating that 677T and 1298C alleles could occur in both cis
      and trans configurations. Combined 677CT/1298CC and 677TT/1298CC genotypes, which
      contain three and four mutant alleles, respectively, were not observed in the
      neonatal group (P=.0402). This suggests decreased viability among fetuses
      carrying these mutations and a possible selection disadvantage among fetuses with
      increased numbers of mutant MTHFR alleles. This is the first report that
      describes the existence of human MTHFR 677CT/1298CC and 677TT/1298CC genotypes
      and demonstrates their potential role in compromised fetal viability.

PMID- 10958764
TI  - Positive influence of the Delta32CCR5 allele on response to highly active
      antiretroviral therapy (HAART) in HIV-1 infected patients.
AB  - The heterozygous 32 base pair deletion of the chemokine receptor 5 (Delta32CCR5)
      has been associated with a more benign course of HIV-1-infection. To study the
      influence of Delta32CCR5 on the response to antiviral therapy we analyzed the
      presence of Delta32CCR5 by PCR in PBMC from 107 randomly selected HIV-1-infected
      patients treated with HAART for at least three months. 24 of 107 patients were
      heterozygous for Delta32CCR5 (22.4%). Before initiation of HAART Delta32CCR5
      heterozygous patients (d/w) did not differ from homozygous CCR5 wild-type
      patients (w/w) regarding viral load and CD4 counts. After a median treatment time
      on HAART of 17.5 months (d/w, range 6-31 months, p = n.s.) or 19 months (w/w,
      range 3-33 months) all 24 patients (100%) with the Delta32CCR5 mutation, but only
      58/83 patients (69.9%) with wild-type CCR5 showed a suppression of HIV-1-viremia
      below 500 copies/ml (p = 0.0020). Furthermore, 20/24 (83.3%) of the Delta32CCR5
      heterozygous patients achieved CD4 counts above 200/microliter, but only 57/83
      (68.7%) of the patients homozygous for CCR5 wild-type (p = 0.011). Our data
      indicate that the presence of heterozygous Delta32CCR5 is associated with a
      better response to HAART suggesting that therapeutic strategies targeting CCR5
      could be of value for a sustained suppression of HIV-1 by HAART.

PMID- 10958763
TI  - A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in
      Stargardt disease and age-related macular degeneration.
AB  - Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and
      young-adult onset and is caused by alterations in the gene encoding the
      photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have
      studied 144 patients with STGD and 220 unaffected individuals ascertained from
      the German population, to complete a comprehensive, population-specific survey of
      the sequence variation in the ABCA4 gene. In addition, we have assessed the
      proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause
      of late-onset blindness, by studying 200 affected individuals with late-stage
      disease. Using a screening strategy based primarily on denaturing gradient gel
      electrophoresis, we have identified in the three study groups a total of 127
      unique alterations, of which 90 have not been previously reported, and have
      classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes
      studied, mutations were identified in 166, resulting in a detection rate of
      approximately 58%. Eight different alleles account for 61% of the identified
      disease alleles, and at least one of these, the L541P-A1038V complex allele,
      appears to be a founder mutation in the German population. When the group with
      AMD and the control group were analyzed with the same methodology, 18 patients
      with AMD and 12 controls were found to harbor possible disease-associated
      alterations. This represents no significant difference between the two groups;
      however, for detection of modest effects of rare alleles in complex diseases, the
      analysis of larger cohorts of patients may be required.

PMID- 10958765
TI  - Incidence of myocardial infarctions in HIV-infected patients between 1983 and
      1998: the Frankfurt HIV-cohort study.
AB  - OBJECTIVE: To investigate whether the use of highly active antiretroviral therapy
      (HAART) is associated with an increased incidence of myocardial infarctions (MI)
      in HIV infected patients. DESIGN: Retrospective analysis of a cohort of 4993 HIV
      infected patients treated at our hospital between January, 1 1983 and December,
      31 1998. The incidence of myocardial infarctions during 4 observation periods
      with different antiretroviral treatment strategies are compared. Possible risk
      factors for MI are evaluated by univariate analysis and using a multiple
      regression model. RESULTS: 29 patients with MI were diagnosed between 1983 and
      1998. The incidence of MI per 1000 patient-years increased from 0.86 (1983-86),
      1.14 (1987-90), 0.59 (1991-94) to 3.41 (1995-98) respectively (p = 0.002). Age
      >40, previous HAART therapy, homo-, or bisexual mode of HIV transmission and
      previous AIDS diagnosis were significantly associated with MI in univariate
      analysis. Age >40 and previous HAART therapy remained significantly associated
      with MI in a multiple regression model. CONCLUSION: The incidence of MI in HIV
      infected patients increased in our cohort after the introduction of HAART.

PMID- 10958766
TI  - Asthma severity, recommended changes of inhaled therapy and exhaled nitric oxide
      in children: a prospective, blinded trial.
AB  - Orally exhaled nitric oxide (ENO) correlates with several variables of airway
      inflammation and might be useful to direct asthma therapy. If this is true, ENO
      should correlate with disease severity and the therapeutic decisions made. - In
      74 children with allergic asthma (age 9.7 years, range 4-16) disease severity was
      determined by history, clinical symptoms, and lung function and inhaled therapy
      was adjusted according to the NIH criteria. ENO was also measured, but the
      patients, their parents and the physicians who made the therapeutic decision were
      left unaware of the results. 31 healthy children served as controls. ENO was
      higher in asthmatics than in controls, but did not differ with asthma severity.
      ENO was weakly correlated with the changes in asthma therapy recommended (r =
      0.303, P = 0.009). ENO values above normal (> 13 ppb) had a sensitivity of 0.67
      and a specificity of 0.65 to predict a step up in therapy. Due to the non-normal
      distribution of ENO there was a substantial overlap between the different groups.
      The lack of correlation with disease severity and the weak prediction of
      physician recommended inhaled therapy, suggest that ENO may be of some value to
      guide asthma therapy. Studies using ENO to direct therapy are necessary for a
      definite answer.

PMID- 10958767
TI  - Detection of K-ras and p53 mutations in bronchoscopically obtained malignant and
      non-malignant tissue from patients with non-small cell lung cancer.
AB  - Molecular screening may increase the likelihood to identify early malignant
      lesions in non-small cell lung cancer. However the presence of gene mutations in
      non-malignant bronchial tissue has remained controversial. The present study was
      carried out to investigate systematically the presence of mutations of the K-ras
      and p53 gene in bronchial biopsies taken during routine bronchoscopy of normal as
      well as tumour tissues from a series of 40 patients with histologically verified
      non-small cell lung cancer (NSCLC). K-ras mutations were analysed with specific
      detection oligonucleotides, p53 mutations were examined by SSCP analysis. In all
      biopsies the wildtype of both K-ras and p53 could be detected. The overall
      frequency of mutations was 14 (35%) with 2 K-ras mutations (5%) and 12 mutations
      of the p53 gene (30%). In 3 cases (1 ras mutation, 2 p53 mutations) the same
      mutation could be shown in the tumour biopsy and in the distant normal control.
      In another case only the normal appearing tissue had a mutation of the p53 gene.
      All other mutations could be detected in the tumour tissue only. Our data confirm
      that K-ras mutations and p53 can be detected not only in malignant but also in
      non-malignant bioptic samples from patients with NSCLC. The use of molecular
      screening for the early detection of lung cancer may be a promising new approach.

PMID- 10958768
TI  - Local and systemic concentrations of pro- and anti-inflammatory cytokines in
      human wounds.
AB  - OBJECTIVE: There is a lack of knowledge on the concentrations of cytokines and
      growth factors in wound healing. The objective was to characterize the pattern of
      local-tissue and systemic peri-and postoperative dynamics of cytokines and growth
      factors in a clinical model of a controlled and comparable operative plastic
      surgery trauma. DESIGN: Prospective clinical study. - SETTING: A University
      Department of Surgery. PATIENTS: 28 patients undergoing an elective reduction
      mammoplasty. MAIN OUTCOME MEASURES: IL-6, IL-8, sTNFR-1 and TGF-beta levels in
      plasma and wound fluid. RESULTS: Levels of cytokines increased only moderately in
      plasma. Cytokine levels in wound fluid were several fold higher. IL-6 in the
      wound fluid peaked at 7 hours after the operation (271 +/- 135.8 pg/ml); IL-8
      after 4 hours (11 +/- 9.4 ng/ml); sTNFR-1 at the second postoperative day (11.1
      +/- 3.4 ng/ml). TGF-beta decreased at the first (15.2 +/- 8.6 ng/ml) and second
      (11.7 +/- 5.0 ng/ml) postoperative day. CONCLUSION: Wound cytokine and growth
      factor levels are markedly higher than the systemic ones indicating a
      compartmentalization of the immune response. Cytokines peaked at different time
      points, probably reflecting the influx of inflammatory cells into the wound and
      the phase of wound healing. Further studies are necessary to clarify the
      mechanism of cytokine release in normal postoperative wounds before therapeutic
      use can be developed.

PMID- 10958769
TI  - Relations between the frequency of the DeltaF 508 mutation and the course of
      pulmonary disease in cystic fibrosis patients infected with Pseudomonas
      aeruginosa.
AB  - The course of pulmonary disease in cystic fibrosis is variable. There are
      controversial data on the impact of the type of mutation on the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene on the course of pulmonary
      disease in CF. Since selected mutations of the CFTR gene appear to be associated
      with relatively mild disease, this study addressed the question whether the
      course of pulmonary disease in CF patients colonized with P. aeruginosa is
      influenced by the frequency of the DeltaF 508 mutation. For this study, we
      assessed FVC and FEV1 in 127 CF patients who attended regularly the Munich CF
      Center over a mean period of 43 +/- 16 (SD) months. Of these 127 patients, 69
      (54.3%) were homozygous for the DeltaF 508 mutation, 42 (33.1%) were compound
      heterozygous for the DeltaF 508 mutation, and 16 (12.6%) did not carry the DeltaF
      508 mutation on either chromosome. In homozygotes 59 (85.5%) out of 69 CF
      patients were colonized with P. aeruginosa as compared with 27 (64.3%) out of 42
      in heterozygotes (p <0.05). The mean age of onset of P. aeruginosa colonization
      was 11.0 years, and there was no difference between the three groups. The mean
      FVC and FEV1 values did not differ significantly between the three genotype
      groups when P. aeruginosa infection was disregarded. However, when only P.
      aeruginosa colonized patients were compared FVC and FEV1 values were lower in
      heterozygotes than in the other two groups both at the beginning and at the end
      of the study. These findings indicate that the course of pulmonary disease in CF
      patients is at least partially influenced by the frequency of the DeltaF 508
      mutation.

PMID- 10958770
TI  - Onconet: a secure infrastructure to improve cancer patients' care.
AB  - The shared care paradigm is the current response to the crisis of industrial
      countries' health systems. The underlying information systems have to meet the
      shared care paradigm of communication and co-operation between all the partners
      involved in. This communication and co-operation must be provided in a secure
      way. The paper presents the required security infrastructure which has been
      analysed, specified, and developed within the TrustHealth projects funded by the
      European Commission. Meeting the challenges of the TrustHealth-2 project for
      large scale implementations of secure real applications, the ONCONET has been
      established in the German federal state of Saxony-Anhalt facilitating the shared
      care of cancer patients. Both security infrastructure and application
      functionalities are demonstrated in some detail.

PMID- 10958772
TI  - Hydrological impact of heinrich events in the subtropical northeast atlantic
AB  - Reconstructing the impact of Heinrich events outside the main belt of ice rafting
      is crucial to understanding the underlying causes of these abrupt climatic
      events. A high-resolution study of a marine sediment core from the Iberian margin
      demonstrates that this midlatitude area was strongly affected both by cooling and
      advection of low-salinity arctic water masses during the last three Heinrich
      events. These paleoclimatic time series reveal the internal complexity of each of
      the last three Heinrich events and illustrate the value of parallel studies of
      the organic and inorganic fractions of the sediments.

PMID- 10958773
TI  - Discrete atom imaging of one-dimensional crystals formed within single-walled
      carbon nanotubes
AB  - The complete crystallography of a one-dimensional crystal of potassium iodide
      encapsulated within a 1.6-nanometer-diameter single-walled carbon nanotube has
      been determined with high-resolution transmission electron microscopy. Individual
      atoms of potassium and iodine within the crystal were identified from a phase
      image that was reconstructed with a modified focal series restoration approach.
      The lattice spacings within the crystal are substantially different from those in
      bulk potassium iodide. This is attributed to the reduced coordination of the
      surface atoms of the crystal and the close proximity of the van der Waals surface
      of the confining nanotube.

PMID- 10958771
TI  - Nucleated conformational conversion and the replication of conformational
      information by a prion determinant.
AB  - Prion proteins can serve as genetic elements by adopting distinct physical and
      functional states that are self-perpetuating and heritable. The critical region
      of one prion protein, Sup35, is initially unstructured in solution and then forms
      self-seeded amyloid fibers. We examined in vitro the mechanism by which this
      state is attained and replicated. Structurally fluid oligomeric complexes appear
      to be crucial intermediates in de novo amyloid nucleus formation. Rapid assembly
      ensues when these complexes conformationally convert upon association with
      nuclei. This model for replicating protein-based genetic information, nucleated
      conformational conversion, may be applicable to other protein assembly processes.

PMID- 10958774
TI  - Unmasking electronic energy transfer of conjugated polymers by suppression of
      O(2) quenching
AB  - The photochemistry of poly[2-methoxy, 5-(2'-ethyl-hexyloxy)-p-phenylene-vinylene]
      (MEH-PPV) has been found to be highly dependent on the presence of O(2), which
      increases singlet exciton quenching dramatically. Spectroscopy on isolated single
      molecules of MEH-PPV in polycarbonate films that exclude O(2) reveals two
      distinct polymer conformations with fluorescence maxima near 555 and 580
      nanometers wavelength, respectively. Time-resolved single-molecule data
      demonstrate that the 580-nanometer conformation exhibits a "landscape" for
      intramolecular electronic energy relaxation with a "funnel" that contains a 580
      nanometer singlet exciton trap at the bottom. The exciton traps can be converted
      to exciton quenchers by reaction with O(2). Conformationally induced, directed
      energy transfer is arguably a critical dynamical process that is responsible for
      many of the distinctive photophysical properties of conjugated polymers.

PMID- 10958775
TI  - Calcium-aluminum-rich inclusions from enstatite chondrites: indigenous or
      foreign?
AB  - The primary mineral assemblages and initial (26)Al/(27)Al ratios of rare calcium
      aluminum-rich inclusions (CAIs) from enstatite (E) chondrites are similar to
      those of CAIs from other chondrite classes. CAIs from all chondrite classes
      formed under oxidizing conditions that are much different from the reducing
      conditions under which the E chondrites formed. Either CAIs formed at an earlier,
      more oxidizing epoch in the region where E chondrites ultimately formed, or they
      formed at a different place in the solar nebula and were transported into the E
      chondrite formation region.

PMID- 10958776
TI  - Incorporation of short-lived (10)Be in a calcium-aluminum-rich inclusion from the
      allende meteorite
AB  - Enrichments in boron-10/boron-11 in a calcium-aluminum-rich inclusion from the
      Allende carbonaceous chondrite are correlated with beryllium/boron in a manner
      indicative of the in situ decay of short-lived beryllium-10. Because this
      radionuclide is produced only by nuclear spallation reactions, its existence in
      early solar system materials attests to intense irradiation processes in the
      solar nebula. The particle fluence inferred from the initial beryllium
      10/beryllium-9 is sufficient to produce other short-lived nuclides, calcium-41
      and manganese-53, found in meteorites, but the high canonical abundance of
      aluminum-26 may still require seeding of the solar system by radioactive stellar
      debris.

PMID- 10958777
TI  - Primordial carbonylated iron-sulfur compounds and the synthesis of pyruvate.
AB  - Experiments exploring the potential catalytic role of iron sulfide at 250 degrees
      C and elevated pressures (50, 100, and 200 megapascals) revealed a facile,
      pressure-enhanced synthesis of organometallic phases formed through the reaction
      of alkyl thiols and carbon monoxide with iron sulfide. A suite of organometallic
      compounds were characterized with ultraviolet-visible and Raman spectroscopy. The
      natural synthesis of such compounds is anticipated in present-day and ancient
      environments wherever reduced hydrothermal fluids pass through iron sulfide
      containing crust. Here, pyruvic acid was synthesized in the presence of such
      organometallic phases. These compounds could have provided the prebiotic Earth
      with critical biochemical functionality.

PMID- 10958778
TI  - Galileo magnetometer measurements: a stronger case for a subsurface ocean at
      Europa.
AB  - On 3 January 2000, the Galileo spacecraft passed close to Europa when it was
      located far south of Jupiter's magnetic equator in a region where the radial
      component of the magnetospheric magnetic field points inward toward Jupiter. This
      pass with a previously unexamined orientation of the external forcing field
      distinguished between an induced and a permanent magnetic dipole moment model of
      Europa's internal field. The Galileo magnetometer measured changes in the
      magnetic field predicted if a current-carrying outer shell, such as a planet
      scale liquid ocean, is present beneath the icy surface. The evidence that
      Europa's field varies temporally strengthens the argument that a liquid ocean
      exists beneath the present-day surface.

PMID- 10958779
TI  - Molecular analysis of plant migration and refugia in the Arctic.
AB  - The arctic flora is thought to have originated during the late Tertiary,
      approximately 3 million years ago. Plant migration routes during colonization of
      the Arctic are currently unknown, and uncertainty remains over where arctic
      plants survived Pleistocene glaciations. A phylogenetic analysis of chloroplast
      DNA variation in the purple saxifrage (Saxifraga oppositifolia) indicates that
      this plant first occurred in the Arctic in western Beringia before it migrated
      east and west to achieve a circumpolar distribution. The geographical
      distribution of chloroplast DNA variation in the species supports the hypothesis
      that, during Pleistocene glaciations, some plant refugia were located in the
      Arctic as well as at more southern latitudes.

PMID- 10958780
TI  - Structure of yeast poly(A) polymerase alone and in complex with 3'-dATP.
AB  - Polyadenylate [poly(A)] polymerase (PAP) catalyzes the addition of a
      polyadenosine tail to almost all eukaryotic messenger RNAs (mRNAs). The crystal
      structure of the PAP from Saccharomyces cerevisiae (Pap1) has been solved to 2.6
      angstroms, both alone and in complex with 3'-deoxyadenosine triphosphate (3'
      dATP). Like other nucleic acid polymerases, Pap1 is composed of three domains
      that encircle the active site. The arrangement of these domains, however, is
      quite different from that seen in polymerases that use a template to select and
      position their incoming nucleotides. The first two domains are functionally
      analogous to polymerase palm and fingers domains. The third domain is attached to
      the fingers domain and is known to interact with the single-stranded RNA primer.
      In the nucleotide complex, two molecules of 3'-dATP are bound to Pap1. One
      occupies the position of the incoming base, prior to its addition to the mRNA
      chain. The other is believed to occupy the position of the 3' end of the mRNA
      primer.

PMID- 10958781
TI  - Differential clustering of CD4 and CD3zeta during T cell recognition.
AB  - Whereas T helper cells recognize peptide-major histocompatibility complex (MHC)
      class II complexes through their T cell receptors (TCRs), CD4 binds to an antigen
      independent region of the MHC. Using green fluorescent protein-tagged chimeras
      and three-dimensional video microscopy, we show that CD4 and TCR-associated
      CD3zeta cluster in the interface coincident with increases in intracellular
      calcium. Signaling-, costimulation-, and cytoskeleton-dependent processes then
      stabilize CD3zeta in a single cluster at the center of the interface, while CD4
      moves to the periphery. Thus, the CD4 coreceptor may serve primarily to "boost"
      recognition of ligand by the TCR and may not be required once activation has been
      initiated.

PMID- 10958782
TI  - Treatment of murine colitis by Lactococcus lactis secreting interleukin-10.
AB  - The cytokine interleukin-10 (IL-10) has shown promise in clinical trials for
      treatment of inflammatory bowel disease (IBD). Using two mouse models, we show
      that the therapeutic dose of IL-10 can be reduced by localized delivery of a
      bacterium genetically engineered to secrete the cytokine. Intragastric
      administration of IL-10-secreting Lactococcus lactis caused a 50% reduction in
      colitis in mice treated with dextran sulfate sodium and prevented the onset of
      colitis in IL-10(-/-) mice. This approach may lead to better methods for cost
      effective and long-term management of IBD in humans.

PMID- 10958783
TI  - Whistle matching in wild bottlenose dolphins (Tursiops truncatus)
AB  - Dolphin communication is suspected to be complex, on the basis of their call
      repertoires, cognitive abilities, and ability to modify signals through vocal
      learning. Because of the difficulties involved in observing and recording
      individual cetaceans, very little is known about how they use their calls. This
      report shows that wild, unrestrained bottlenose dolphins use their learned
      whistles in matching interactions, in which an individual responds to a whistle
      of a conspecific by emitting the same whistle type. Vocal matching occurred over
      distances of up to 580 meters and is indicative of animals addressing each other
      individually.

PMID- 10958784
TI  - PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected].
AB  - Chromosomal translocations that encode fusion oncoproteins have been observed
      consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most
      common human cancers. Here, we report that t(2;3)(q13;p25), a translocation
      identified in a subset of human thyroid follicular carcinomas, results in fusion
      of the DNA binding domains of the thyroid transcription factor PAX8 to domains A
      to F of the peroxisome proliferator-activated receptor (PPAR) gamma1. PAX8
      PPARgamma1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas
      but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular
      hyperplasias. PAX8-PPARgamma1 inhibited thiazolidinedione-induced transactivation
      by PPARgamma1 in a dominant negative manner. The experiments demonstrate an
      oncogenic role for PPARgamma and suggest that PAX8-PPARgamma1 may be useful in
      the diagnosis and treatment of thyroid carcinoma.

PMID- 10958785
TI  - Regulated cleavage of a contact-mediated axon repellent.
AB  - Contact-mediated axon repulsion by ephrins raises an unresolved question: these
      cell surface ligands form a high-affinity multivalent complex with their
      receptors present on axons, yet rather than being bound, axons can be rapidly
      repelled. We show here that ephrin-A2 forms a stable complex with the
      metalloprotease Kuzbanian, involving interactions outside the cleavage region and
      the protease domain. Eph receptor binding triggered ephrin-A2 cleavage in a
      localized reaction specific to the cognate ligand. A cleavage-inhibiting mutation
      in ephrin-A2 delayed axon withdrawal. These studies reveal mechanisms for
      protease recognition and control of cell surface proteins, and, for ephrin-A2,
      they may provide a means for efficient axon detachment and termination of
      signaling.

PMID- 10958786
TI  - Function of an axonal chemoattractant modulated by metalloprotease activity.
AB  - The axonal chemoattractant netrin-1 guides spinal commissural axons by activating
      its receptor DCC (Deleted in Colorectal Cancer). We have found that chemical
      inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in
      vitro. We have also found that DCC is a substrate for metalloprotease-dependent
      ectodomain shedding, and that the inhibitors block proteolytic processing of DCC
      and cause an increase in DCC protein levels on axons within spinal cord explants.
      Thus, potentiation of netrin activity by inhibitors may result from stabilization
      of DCC on the axons, and proteolytic activity may regulate axon migration by
      controlling the number of functional extracellular axon guidance receptors.

PMID- 10958787
TI  - Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad
      proteins.
AB  - Cyclin-dependent kinase 7 (Cdk7) forms a trimeric complex with cyclin H and Mat1
      to form the mammalian Cdk-activating kinase, CAK, as well as a part of the basal
      transcription factor TFIIH, where Cdk7 phosphorylates the C-terminal domain (CTD)
      of the large subunit of RNA polymerase II. Here, we report a novel interaction
      between Cdk7 and a histidine triad (HIT) family protein, Hint/PKCI-1. This
      interaction was initially observed in a yeast two-hybrid study and subsequently
      verified by co-immunoprecipitation and subcellular localization studies, where
      overexpression of Cdk7 leads to partial relocalization of Hint to the nucleus.
      The physical association is independent of cyclin H binding or Cdk7 kinase
      activity and is conserved between the related Sacharomyces cerevisiae CTD kinase
      Kin28 and the HIT protein Hnt1. Furthermore, combination of a disruption of HNT1
      and a KIN28 temperature-sensitive allele in S. cerevisiae led to highly elongated
      cell morphology and reduced colony formation, indicating a genetic interaction
      between KIN28 and HNT1. The physical and genetic interactions of Hint and Hnt1
      with Cdk7 and Kin28 suggest a role for this class of histidine triad proteins in
      the regulation of Cdk7 and Kin28 functions.

PMID- 10958788
TI  - Cross-linking of wild-type and mutant alpha 2-antiplasmins to fibrin by activated
      factor XIII and by a tissue transglutaminase.
AB  - Human alpha(2)-antiplasmin (alpha(2)AP), the main inhibitor of plasmin-mediated
      fibrinolysis, is a substrate for plasma transglutaminase, also termed activated
      factor XIII (FXIIIa). Of 452 amino acids in alpha(2)AP, only Gln(2) is believed
      to be a fibrin-cross-linking (or FXIIIa-reactive) site. Kinetic efficiencies
      (k(cat)/K(m)((app))) of FXIIIa and the guinea pig liver tissue transglutaminase
      (tTG) and reactivities of Gln substrate sites were compared for recombinant wild
      type alpha(2)AP (WT-alpha(2)AP) and Q2A mutant alpha(2)AP (Q2A-alpha(2)AP).
      [(14)C]Methylamine incorporation showed the k(cat)/K(m)((app)) of FXIIIa to be 3
      fold greater than that of tTG for WT-alpha(2)AP. With FXIIIa or tTG catalysis,
      [(14)C]methylamine was incorporated into Q2A-alpha(2)AP, indicating that WT
      alpha(2)AP has more than one Gln cross-linking site. To identify transglutaminase
      reactive sites in WT-alpha(2)AP or Q2A-alpha(2)AP, each was labeled with 5
      (biotinamido)pentylamine by FXIIIa or tTG catalysis. After each labeled
      alpha(2)AP was digested by trypsin, sequence and mass analyses of each labeled
      peptide showed that 4 of 35 Gln residues were labeled with the following
      reactivities: Gln(2) > Gln(21) > Gln(419) > Gln(447). Q(2)A-alpha(2)AP was also
      labeled at Gln(21) > Gln(419) > Gln(447), but became cross-linked to fibrin by
      FXIIIa or tTG at approximately one-tenth the rate for WT-alpha(2)AP. These
      results show that alpha(2)AP is a better substrate for FXIIIa than for this
      particular tTG, but that either enzyme involves the same Gln substrate sites in
      alpha(2)AP and yields the same order of reactivities.

PMID- 10958789
TI  - Polyarginines are potent furin inhibitors.
AB  - The ubiquitous serine endoprotease furin has been implicated in the activation of
      bacterial toxins and viral glycoproteins as well as in the metastatic progression
      of certain tumors. Although high molecular mass bioengineered serpin inhibitors
      have been well characterized, no small nontoxic nanomolar inhibitors have been
      reported to date. Here we describe the identification of such inhibitors using
      positional scanning amidated and acetylated synthetic l- and d-hexapeptide
      combinatorial libraries. The results indicated that l-Arg or l-Lys in all
      positions generated the most potent inhibitors. However, further investigation
      revealed that the peptide terminating groups hindered inhibition. Consequently, a
      series of non-amidated and acetylated polyarginines was synthesized. The most
      potent inhibitor identified, nona-l-arginine, had a K(i) for furin of 40 nm. The
      K(i) values for the related convertases PACE4 and prohormone convertase-1 (PC1)
      were 110 nm and 2.5 microm, respectively. Although nona-l-arginine was cleaved by
      furin, the major products after a 6-h incubation at 37 degrees C were hexa- and
      hepta-l-arginines, both of which retained the great majority of their potency and
      specificity against furin. Hexa-d-arginine was as potent and specific a furin
      inhibitor as hexa-l-arginine (K(i) values of hexa-d-arginine: 106 nm, 580 nm, and
      13.2 microm for furin, PACE4, and PC1, respectively). PC2 was not inhibited by
      any polyarginine tested; indeed, PC2 showed an increase in activity of up to 140%
      of the control in the presence of l-polyarginines. Data are also presented that
      show extended subsite recognition by furin and PC2. Whereas N-terminal
      acetylation was found to reduce the inhibitory potency of the l-hexapeptide
      LLRVKR against furin 8-fold, C-terminal amidation reduced the potency < 2-fold.
      Conversely, N-terminal acetylation increased the potency against PC2 nearly 3
      fold, whereas C-terminal amidation of the same peptide increased the potency by a
      factor of 1.6. Our data indicate that non-acetylated, poly-d-arginine-derived
      molecules may represent excellent lead compounds for the development of
      therapeutically useful furin inhibitors.

PMID- 10958790
TI  - Functional heterogeneity in the zinc fingers of metalloregulatory protein metal
      response element-binding transcription factor-1.
AB  - Metal response element-binding transcription factor-1 (MTF-1) is a unique, zinc
      inducible transcription factor that binds to metal response elements in the
      metallothionein promoter and activates transcription in response to metals and
      oxidative stress. MTF-1 contains six zinc fingers of the Cys(2)-His(2) type. It
      was previously shown that MTF-1 is reversibly activated to bind DNA in response
      to changes in zinc status, unlike other zinc finger transcription factors, which
      do not appear to be reversibly activated by zinc in the cellular environment.
      Here we show that zinc fingers 2-4 constitute the core DNA-binding domain,
      whereas fingers 5 and 6 appear to be unnecessary for DNA binding in vitro.
      Deletion of finger 1 resulted in a protein that bound DNA constitutively in
      vitro. Furthermore, transfer of MTF-1 finger 1 to a position immediately
      preceding the three zinc fingers of Sp1 resulted in a chimeric protein that
      required exogenous zinc to activate DNA binding in vitro, unlike native Sp1,
      which binds DNA constitutively. Transient transfection experiments demonstrated
      that intact MTF-1 activated a reporter 2.5-4-fold above basal levels after metal
      treatment in mouse MTF-1 knockout cells, Drosophila SL2 cells, and yeast.
      However, the metal response was lost in all three systems when finger 1 was
      deleted, but was unaffected by deletion of fingers 5 and 6. These data suggest
      that finger 1 of MTF-1 constitutes a unique metal-sensing domain that, in
      cooperation with the transactivation domains, produces a zinc-sensing
      metalloregulatory transcription factor.

PMID- 10958791
TI  - Mammalian GFRalpha -4, a divergent member of the GFRalpha family of coreceptors
      for glial cell line-derived neurotrophic factor family ligands, is a receptor for
      the neurotrophic factor persephin.
AB  - Four members of the glial cell line-derived neurotrophic factor family have been
      identified (GDNF, neurturin, persephin, and enovin/artemin). They bind to a
      specific membrane-anchored GDNF family receptor as follows: GFRalpha-1 for GDNF,
      GFRalpha-2 for neurturin, GFRalpha-3 for enovin/artemin, and (chicken) GFRalpha-4
      for persephin. Subsequent signaling occurs through activation of a common
      transmembrane tyrosine kinase, cRET. GFRalpha-4, the coreceptor for persephin,
      was previously identified in chicken only. We describe the cloning and
      characterization of a mammalian persephin receptor GFRalpha-4. The novel GFRalpha
      receptor is substantially different in sequence from all known GFRalphas,
      including chicken GFRalpha-4, and lacks the first cysteine-rich domain present in
      all previously characterized GFRalphas. At least two different GFRalpha-4 splice
      variants exist in rat tissues, differing at their respective COOH termini.
      GFRalpha-4 mRNA is expressed at low levels in different brain areas in the adult
      as well as in some peripheral tissues including testis and heart. Recombinant rat
      GFRalpha-4 variants were expressed in mammalian cells and shown to be at least
      partially secreted from the cells. Persephin binds specifically and with high
      affinity (K(D) = 6 nm) to the rat GFRalpha-4 receptor, but no cRET activation
      could be demonstrated. Although the newly characterized mammalian GFRalpha-4
      receptor is structurally divergent from previously characterized GFRalpha family
      members, we suggest that it is a mammalian orthologue of the chicken persephin
      receptor. This discovery will allow a more detailed investigation of the
      biological targets of persephin action and its potential involvement in diseases
      of the nervous system.

PMID- 10958792
TI  - Effect of extracellular signal-regulated kinase on p53 accumulation in response
      to cisplatin.
AB  - The p53 tumor suppressor protein is a transcription factor that plays a major
      role in the DNA damage response. After DNA damage, p53 levels increase due
      primarily to stabilization of the protein. The molecular mechanisms leading to
      stabilization of p53 after DNA damage have not been completely elucidated.
      Recently we reported that cisplatin treatment activated extracellular signal
      regulated kinase 1 and 2 (ERK1/2) and that inhibition of ERK1/2 resulted in
      enhanced sensitivity to cisplatin. In the present study, we examined the
      potential role of ERK1/2 activation in regulation of the p53 response to
      cisplatin. In the ovarian carcinoma cell line A2780, inhibition of ERK1/2
      activation with the mitogen-activated protein kinase/ERK kinase 1 (MEK1)
      inhibitor PD98059 resulted in decreased p53 protein half-life and diminished
      accumulation of p53 protein during exposure to cisplatin. We also demonstrated
      that p53 protein co-immunoprecipitated with ERK1/2 protein and was phosphorylated
      by activated recombinant murine ERK2 in vitro. Furthermore, PD98059 decreased the
      phosphorylation of p53 at serine 15 during cisplatin exposure, suggesting that
      ERK1/2 mediates in part phosphorylation of p53 during the cisplatin DNA response.
      These results strongly suggest that cisplatin-induced ERK activation is an up
      stream regulator of the p53 response to DNA damage caused by cisplatin.

PMID- 10958793
TI  - Heterogeneous ribonucleoprotein A1 is part of an exon-specific splice-silencing
      complex controlled by oncogenic signaling pathways.
AB  - Regulation of alternative pre-mRNA splicing, recognized as increasingly important
      in causing human disease, was studied using the CD44 gene, whose splice variants
      have been implicated in tumor progression. We identified heterogeneous
      ribonucleoprotein (hnRNP) A1 as a protein interacting in vitro and in vivo with
      regulatory splice elements in CD44 variant exon v5. Transient overexpression of
      hnRNP A1 prevented v5 exon inclusion, dependent on the exonic elements. HnRNP A1
      dependent repression was exon-specific and could be relieved by coexpression of
      oncogenic forms of Ras and Cdc42. The results define hnRNP A1 as a decisive part
      of an oncogene-regulated splice-silencing complex, which can select between
      multiple alternatively spliced exons.

PMID- 10958794
TI  - The role of histidines in the acetate kinase from Methanosarcina thermophila.
AB  - The role of histidine in the catalytic mechanism of acetate kinase from
      Methanosarcina thermophila was investigated by diethylpyrocarbonate inactivation
      and site-directed mutagenesis. Inactivation was accompanied by an increase in
      absorbance at 240 nm with no change in absorbance at 280 nm, and treatment of the
      inactivated enzyme with hydroxylamine restored 95% activity, results that
      indicated diethylpyrocarbonate inactivates the enzyme by the specific
      modification of histidine. The substrates ATP, ADP, acetate, and acetyl phosphate
      protected against inactivation suggesting at least one active site where
      histidine is modified. Correlation of residual activity with the number of
      histidines modified, as determined by absorbance at 240 nm, indicated that a
      maximum of three histidines are modified per subunit, two of which are essential
      for full inactivation. Comparison of the M. thermophila acetate kinase sequence
      with 56 putative acetate kinase sequences revealed eight highly conserved
      histidines, three of which (His-123, His-180, and His-208) are perfectly
      conserved. Diethylpyrocarbonate inactivation of the eight histidine --> alanine
      variants indicated that His-180 and His-123 are in the active site and that the
      modification of both is necessary for full inactivation. Kinetic analyses of the
      eight variants showed that no other histidines are important for activity.
      Analysis of additional His-180 variants indicated that phosphorylation of His-180
      is not essential for catalysis. Possible functions of His-180 are discussed.

PMID- 10958795
TI  - Mullerian inhibiting substance inhibits ovarian cell growth through an Rb
      independent mechanism.
AB  - Mullerian inhibiting substance (MIS), a transforming growth factor-beta family
      member, causes regression of the Mullerian duct in male embryos. MIS
      overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth
      of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in
      postnatal development of the ovary. This report describes a mechanism for MIS
      mediated growth inhibition in both a human epithelial ovarian cancer cell line
      and a cell line derived from normal ovarian surface epithelium, which is the
      origin of human epithelial ovarian cancers. MIS-treated cells accumulated in the
      G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up
      regulated the cyclin-dependent kinase inhibitor p16 through an MIS type II
      receptor-mediated mechanism and inhibited growth in the absence of detectable or
      inactive Rb protein. Prolonged treatment with MIS down-regulated the Rb-related
      protein p130 and increased the Rb family-regulated transcription factor E2F1,
      overexpression of which inhibited growth. These findings demonstrate that p16 is
      required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor
      cells and suggest that up-regulation of E2F1 also plays a role in this process.

PMID- 10958796
TI  - The uncoupling protein-3 gene is transcribed from tissue-specific promoters in
      humans but not in rodents.
AB  - Uncoupling protein-3 (UCP3), a mitochondrial membrane transporter, is a candidate
      effector of thermogenesis. Even though mice with targeted disruption of the UCP3
      gene are not obese, indirect evidence suggests that this protein contributes to
      the control of energy expenditure in humans. We therefore characterized the human
      UCP3 gene and compared it with its rodent homologues with respect to tissue
      specific expression and regulatory regions. Like rodent UCP3, human UCP3 was
      expressed in skeletal muscle and brown adipose tissue (BAT). The short mRNA
      isoform, UCP3(S), which is absent in rodents, was relatively more abundant in
      human skeletal muscle in comparison to human BAT. Two tissue-specific
      transcription start sites for each skeletal muscle and BAT were delineated for
      human UCP3. Tissue-specific transcript initiation was maintained in both tissues
      and cultured cells over a wide range of expression levels. In contrast, rodent
      transcripts were initiated at the same site in BAT and muscle tissue. Comparison
      of human and rodent promoters indicated a rapid phylogenetic evolution suggesting
      functional diversification. The transcription from tissue-specific promoters in
      humans is a novel finding that may provide the basis for therapeutic
      interventions aimed at regulating energy expenditure in a tissue-specific
      fashion.

PMID- 10958797
TI  - Intracellular sodium modulates mitochondrial calcium signaling in vascular
      endothelial cells.
AB  - We have investigated the role of extramitochondrial Na(+) for the regulation of
      mitochondrial Ca(2+) concentration ([Ca(2+)](m)) in permeabilized single vascular
      endothelial cells. [Ca(2+)](m) was measured by loading the cells with the
      membrane-permeant Ca(2+) indicator fluo-3/AM and subsequent removal of
      cytoplasmic fluo-3 by surface membrane permeabilization with digitonin. An
      elevation of extramitochondrial Ca(2+) resulted in a dose-dependent increase in
      the rate of Ca(2+) accumulation into mitochondria (k(0.5) = 3 microm) via the
      mitochondrial Ca(2+) uniporter. In the presence of 10 mm extramitochondrial Na(+)
      ([Na(+)](em)), repetitive application of brief pulses of high Ca(2+) (2-10
      microm) to simulate cytoplasmic [Ca(2+)] oscillations caused transient increases
      of [Ca(2+)](m) characterized by a fast rising phase that was followed by a slow
      decay. Removal of extramitochondrial Na(+) or inhibition of mitochondrial
      Na(+)/Ca(2+) exchange with clonazepam blocked mitochondrial Ca(2+) efflux and
      resulted in a net accumulation of Ca(2+) by the mitochondria. Half-maximal
      activation of mitochondrial Na(+)/Ca(2+) exchange occurred at [Na(+)](em) = 4.4
      mm, which is well within the physiological range of cytoplasmic [Na(+)]. This
      study provides evidence that Ca(2+) efflux from the mitochondria in vascular
      endothelial cells occurs solely via Na(+)/Ca(2+) exchange and emphasizes the
      important role of intracellular Na(+) for mitochondrial Ca(2+) regulation.

PMID- 10958799
TI  - The G protein-coupled receptor CL1 interacts directly with proteins of the Shank
      family.
AB  - PDZ domains play a pivotal role in the synaptic localization of ion channels,
      receptors, signaling enzymes, and cell adhesion molecules. These domains mediate
      protein-protein interactions via the recognition of a conserved sequence motif at
      the extreme C terminus of their target proteins. By means of a yeast two-hybrid
      screen using the C terminus of the G protein-coupled alpha-latrotoxin receptor
      CL1 as bait, three PDZ domain proteins of the Shank family were identified. These
      proteins belong to a single protein family characterized by a common domain
      organization. The PDZ domain is highly conserved among the family members,
      significantly different from other known PDZ domains, and specifically binds to
      the C terminus of CL1. Shank1 and CL1 are expressed primarily in brain, and both
      proteins co-enrich in the postsynaptic density. Furthermore, Shank1 induces a
      clustering of CL1 in transfected cells, strongly supporting an interaction of
      both proteins in vivo.

PMID- 10958798
TI  - Integrin activation and focal complex formation in cardiac hypertrophy.
AB  - Cardiac hypertrophy is characterized by both remodeling of the extracellular
      matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased
      expression and cytoskeletal association of the ECM proteins fibronectin and
      vitronectin in pressure-overloaded feline myocardium. These changes are
      accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase
      (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter
      proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated
      kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of
      fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes
      cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under
      both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded
      cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD
      stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c
      Src association occurred without Tyr-416 phosphorylation and p130(Cas)
      association. Therefore, c-Src activation is not required for its cytoskeletal
      binding but may be important for additional phosphorylation of FAK. Overall, our
      study suggests that multiple signaling pathways originate in pressure-overloaded
      heart following integrin engagement with ECM proteins, including focal complex
      formation and ERK1/2 activation, and many of these pathways can be activated in
      cardiomyocytes via RGD-stimulated integrin activation.

PMID- 10958800
TI  - The role of active site arginines of sorghum NADP-malate dehydrogenase in
      thioredoxin-dependent activation and activity.
AB  - The activation of sorghum NADP-malate dehydrogenase is initiated by
      thiol/disulfide interchanges with reduced thioredoxin followed by the release of
      the C-terminal autoinhibitory extension and a structural modification shaping the
      active site into a high efficiency and high affinity for oxaloacetate
      conformation. In the present study, the role of the active site arginines in the
      activation and catalysis was investigated by site-directed mutagenesis and
      arginyl-specific chemical derivatization using butanedione. Sequence and mass
      spectrometry analysis were used to identify the chemically modified groups. Taken
      together, our data reveal the involvement of Arg-134 and Arg-204 in oxaloacetate
      coordination, suggest an indirect role for Arg-140 in substrate binding and
      catalysis, and clearly confirm that Arg-87 is implicated in cofactor binding. In
      contrast with NAD-malate dehydrogenase, no lactate dehydrogenase activity could
      be promoted by the R134Q mutation. The decreased susceptibility of the activation
      of the R204K mutant to NADP and its increased sensitivity to the histidine
      specific reagent diethylpyrocarbonate indicated that Arg-204 is involved in the
      locking of the active site. These results are discussed in relation with the
      recently published NADP-MDH three-dimensional structures and the previously
      established three-dimensional structures of NAD-malate dehydrogenase and lactate
      dehydrogenase.

PMID- 10958801
TI  - Movement of the helical domain of the epsilon subunit is required for the
      activation of thermophilic F1-ATPase.
AB  - The inhibitory effect of epsilon subunit in F(1)-ATPase from thermophilic
      Bacillus PS3 was examined focusing on the structure-function relationship. For
      this purpose, we designed a mutant for epsilon subunit similar to the one
      constructed by Schulenberg and Capaldi (Schulenberg, B., and Capaldi, R. A.
      (1999) J. Biol. Chem. 274, 28351-28355). We introduced two cysteine residues at
      the interface of N-terminal beta-sandwich domain (S48C) and C-terminal alpha
      helical domain (N125C) of epsilon subunit. The alpha(3)beta(3)gammaepsilon
      complex containing the reduced form of this mutant epsilon subunit showed
      suppressed ATPase activity and gradual activation during the measurement. This
      activation pattern was similar to the complex with the wild type epsilon subunit.
      The conformation of the mutant epsilon subunit must be fixed and similar to the
      reported three-dimensional structure of the isolated epsilon subunit, when the
      intramolecular disulfide bridge was formed on this subunit by oxidation. This
      oxidized mutant epsilon subunit could form the alpha(3)beta(3)gammaepsilon
      complex but did not show any inhibitory effect. The complex was converted to the
      activated state, and the cross-link in the mutant epsilon subunit in the complex
      was efficiently formed in the presence of ATP-Mg, whereas no cross-link was
      observed without ATP-Mg, suggesting the conformation of the oxidized mutant
      epsilon subunit must be similar to that in the activated state complex. A non
      hydrolyzable analog of ATP, 5'-adenylyl-beta,gamma-imidodiphosphate, could
      stimulate the formation of the cross-link on the epsilon subunit. Furthermore,
      the cross-link formation was stimulated by nucleotides even when this mutant
      epsilon subunit was assembled with a mutant alpha(3)beta(3)gamma complex lacking
      non-catalytic sites. These results indicate that binding of ATP to the catalytic
      sites induces a conformational change in the epsilon subunit and triggers
      transition of the complex from the suppressed state to the activated state.

PMID- 10958802
TI  - Phytosterols as anticancer dietary components: evidence and mechanism of action.
AB  - Phytosterols (PS) or plant sterols are structurally similar to cholesterol. The
      most common PS are beta-sitosterol, campesterol and stigmasterol. Epidemiologic
      and experimental studies suggest that dietary PS may offer protection from the
      most common cancers in Western societies, such as colon, breast and prostate
      cancer. This review summarizes the findings of these studies and the possible
      mechanisms by which PS offer this protection. These include the effect of PS on
      membrane structure and function of tumor and host tissue, signal transduction
      pathways that regulate tumor growth and apoptosis, immune function of the host
      and cholesterol metabolism by the host. In addition, suggestions for future
      studies to fill the gaps in our knowledge have been given.

PMID- 10958803
TI  - Starvation impairs antioxidant defense in fatty livers of rats fed a choline
      deficient diet.
AB  - Although fatty liver (FL) is considered an innocuous condition, the frequent
      incidence of graft failure when FL are transplanted has renewed interest in the
      intracellular disorders causative of or consequent to fatty degeneration.
      Oxidative stress and nutritional status modulate the tolerance to reperfusion
      injury in control livers (CL), but very little is known in the case of FL. This
      study was designed to compare the oxidative balance in CL and FL from fed and
      food-deprived rats. Serum and liver samples were collected from fed and starved
      (18 h) rats with CL or FL induced by a choline-deficient diet. Hepatic injury was
      assessed by transaminase activities and histology. The hepatic concentrations of
      glutathione (GSH), vitamin C, alpha-tocopherol, thiobarbituric acid-reactive
      substances (TBARS) and protein carbonyls (PC) were measured. Fed rats with FL had
      significantly greater TBARS and lower alpha-tocopherol and vitamin C levels than
      those with CL, whereas GSH and PC concentrations were not affected. Starvation
      impaired the oxidative balance in both groups. However, compared with the other
      groups, FL from food-deprived rats generally had the lowest hepatic
      concentrations of alpha-tocopherol, vitamin C and GSH. Unlike in CL, protein
      oxidation occurred in FL. These data indicate that fatty liver induced by
      consumption of a choline-deficient diet is associated with a lower level of
      antioxidants, which results in lipid peroxidation. Starvation further affects
      these alterations and extends the damage to proteins. In conclusion, steatosis
      and starvation may act synergistically on the depletion of antioxidants,
      predisposing fatty livers to a reduced tolerance to oxidative injury.

PMID- 10958804
TI  - Dietary psyllium increases expression of ileal apical sodium-dependent bile acid
      transporter mRNA coordinately with dose-responsive changes in bile acid
      metabolism in rats.
AB  - Psyllium (PSY), a type of dietary fiber containing mainly soluble components, has
      been shown to decrease serum cholesterol concentrations in several species;
      however, mechanisms involved are not clearly defined. Four groups of 10 rats were
      fed semipurified diets containing 10% dietary fiber from cellulose and/or PSY for
      21 d. Increasing levels of PSY were fed (0,3.33, 6.67 and 10% PSY) with the
      remaining 10% made up with cellulose. Liver cholesterol, cholesterol 7alpha
      hydroxylase (CYP7A) activity and mRNA, 3-hydroxy-3-methylglutaryl CoA reductase
      (HMGR) mRNA, ileal apical sodium-dependent bile acid transporter (ASBT) mRNA,
      fecal bile acids and total steroids, and intestinal bile acid content were
      measured. All variables responded in a dose-dependent manner to PSY in the diet.
      Total liver cholesterol content was significantly reduced in all groups fed PSY
      compared to cellulose-fed controls [138(a), 105(b), 105(b) and 93(c) micromol
      (SEM = 4.2) for 0, 3.33, 6.67 and 10% PSY, respectively]. Activity of CYP7A was
      significantly greater in all groups fed PSY compared to the cellulose-fed
      controls [6.36(c), 16.92(b), 15.28(b) and 20.37(a) pmol x min(-1) x mg protein(
      1) (SEM = 3.19) for 0, 3.33, 6.67 and 10% PSY, respectively]. These differences
      in CYP7A activity were similar to differences in CYP7A, HMGR and ASBT mRNA
      levels. Fecal bile acid and total steroid excretion as well as total intestinal
      bile acids were significantly greater in rats fed PSY-containing diets compared
      to 0% PSY-fed rats. These results suggest that the reduction in liver cholesterol
      involves modulating the size and composition of the bile acid pool via regulation
      of ileal ASBT, CYP7A and HMGR mRNA levels.

PMID- 10958805
TI  - Mitochondrial transcription factor A is increased but expression of ATP synthase
      beta subunit and medium-chain acyl-CoA dehydrogenase genes are decreased in
      hearts of copper-deficient rats.
AB  - The mechanism(s) by which impaired mitochondrial respiratory function and the
      accumulation of lipid droplets and mitochondria in hearts of copper-deficient
      rats occur remains unclear. It is not known whether specific components of the
      regulatory pathway involved in mitochondrial biogenesis, such as mitochondrial
      transcription factor A (mtTFA) and nuclear respiratory factors 1 and 2 (NRF-1 and
      NRF-2), are activated in copper deficiency. Little is known about gene expression
      of enzymes involved in fatty acid oxidation (FAO) in hearts of copper-deficient
      rats. Male weanling rats were fed copper-adequate (CuA), copper-deficient (CuD)
      or pair-fed (CuP) diets for 5 wk. Mitochondria and lipid droplet volume densities
      from electron micrographs were greater and there was an elevation in the mtTFA
      protein level in hearts of copper-deficient rats. DNA binding activities of NRF-1
      and NRF-2 did not differ among the groups. Northern blot analysis of cardiac
      tissue revealed that transcripts of F(1)F(0)-ATP synthase subunit c were greater,
      but mRNA levels of ATP synthase beta subunit and the FAO enzyme, medium-chain
      acyl-CoA dehydrogenase (MCAD), were lower in hearts of copper-deficient rats.
      Long-chain acyl-CoA dehydrogenase (LCAD) mRNA levels did not differ among
      treatment groups. These results suggest that certain components of the
      mitochondrial biogenesis program are activated in hearts of copper-deficient
      rats. F(1)F(0)-ATP synthase beta subunit and MCAD transcript levels remain low,
      which may contribute to impaired mitochondrial respiratory function, decreased
      fatty acid utilization and lipid droplet accumulation in hearts of copper
      deficient rats.

PMID- 10958806
TI  - Hepatic LDL receptor mRNA in rats is increased by dietary mushroom (Agaricus
      bisporus) fiber and sugar beet fiber.
AB  - Plasma cholesterol concentration is reduced by feeding some dietary fibers and
      mushroom fruit body, but the mechanism is not fully understood. We examined the
      effects of mushroom (Agaricus bisporus) fiber and sugar beet fiber on serum
      cholesterol and hepatic LDL receptor mRNA in rats. Rats were fed a cholesterol
      free diet with 50 g/kg cellulose powder (CP), 50 g/kg mushroom (Agaricus
      bisporus) fiber (MSF) or 50 g/kg sugar beet fiber (BF) for 4 wk. There were no
      significant differences in the body weight, food intake and cecum weight among
      the groups. The relative liver weight in the CP group was significantly greater
      than that in the MSF and BF groups. The cecal pH in the CP and MSF groups was
      significantly higher than that in the BF group. Cecal acetic acid, butyric acid
      and total short-chain fatty acid (SCFA) concentrations in the BF group were
      significantly higher than those in the other groups. The serum total cholesterol,
      VLDL + intermediate density lipoprotein (IDL) + LDL cholesterol concentrations in
      the CP group were significantly greater than those in the MSF and BF groups. The
      HDL cholesterol concentration in the MSF group was significantly lower than that
      in the CP group. The hepatic LDL receptor mRNA level in the MSF and BF groups was
      significantly higher than that in the CP group. The results of this study
      demonstrate that mushroom fiber and sugar beet fiber lowered the serum total
      cholesterol level by enhancement of the hepatic LDL receptor mRNA.

PMID- 10958807
TI  - Dietary carbohydrate source and energy intake influence the expression of
      pancreatic alpha-amylase in lambs.
AB  - In ruminants, pancreatic alpha-amylase is the primary enzyme responsible for the
      initial hydrolysis of alpha-linked glucose in the small intestinal lumen. The
      objective of this experiment was to examine the effects of altered dietary starch
      and energy supply on the expression of pancreatic alpha-amylase mRNA, protein and
      activity in lambs. Wether lambs (n = 24; 28 +/- 0.5 kg body weight) were fed low
      or high starch diets at 1.2 or 1.8 x net energy of maintenance for at least 28 d
      before tissue collection. Lambs fed the high energy/high starch diet tended to
      have more pancreatic alpha-amylase protein (54.5 kDa; P: = 0.08) and had greater
      activity (P: = 0.03), but alpha-amylase mRNA (1.6 kb) tended to be lower (P: =
      0.17). Additionally, rumen fluid total short-chain fatty acid concentration was
      greater (P: = 0.04) and plasma glucose concentration tended to be greater (P: =
      0.07) in lambs fed the high energy/high starch diet. However, pancreatic
      trypsinogen protein (25. 5 kDa) and jejunal maltase activity were not influenced
      by dietary treatment, suggesting that different regulatory systems are involved
      in regulating the tissue protein or activity levels of these two enzymes compared
      with alpha-amylase. These data suggest that dietary regulation of pancreatic
      alpha-amylase expression in ruminants is complex and probably regulated by
      transcriptional and post-transcriptional events.

PMID- 10958809
TI  - Partial sequence and expression of the gene for and activity of the sodium
      glucose transporter in the small intestine of fed, starved and refed chickens.
AB  - A 970 bp cDNA Na(+)/glucose cotransporter (SGLT1) was isolated and sequenced from
      chicken jejunum by reverse transcriptase polymerase chain reaction (RT-PCR) using
      primers based on conserved regions. Using the 970 bp PCR product as a specific
      probe, Northern Blot hybridization indicated a transcript of ca. 4 kb. The
      isolated chicken intestinal SGLT1 cDNA was used to quantitate mRNA expression.
      Glucose uptake activity and kinetics were determined in brush border membrane
      vesicles (BBMV) from jejunum tissue of chickens which were either fed, food
      deprived or refed following food deprivation. Net glucose uptake to BBMV was
      higher (P: < 0.02) in the control and refed chicks (149 +/- 11.9, 139.6 +/- 7.43
      pmol x mg protein(-1) x s(-1)) than in food-deprived chicks (107 +/- 4.23 pmol x
      mg protein(-1) x s(-1)). The k(m) (150 micromol/L) and V:max (1111.1 pmol x mg
      protein(-1) x s(-1)) were higher in the food-deprived chicks compared to control
      and refed birds (25, 24 micromol/L and 227,142 pmol x mg protein(-1) x s(-1),
      respectively). Expression of SGLT1 mRNA was significantly enhanced in the food
      deprived and refed birds. In food-deprived chicks the lower affinity and higher
      activity of the SGLT1 transporter for glucose were accompanied by higher
      expression of mRNA which might indicate that the transporter was upregulated by
      low substrate concentration. Quantification of expression of intestinal mRNA of
      SGLT1 provides important information concerning control of nutrient uptake.

PMID- 10958808
TI  - Regulation of intestinal apolipoprotein B mRNA editing levels by a zinc-deficient
      diet and cDNA cloning of editing protein in hamsters.
AB  - This study was conducted to investigate the influence of dietary zinc on
      intestinal apoB mRNA editing in hamsters. Apolipoprotein B-48 (apoB-48) is
      synthesized from the same gene as apoB-100 by a post-transcriptional, site
      specific cytidine deamination, a process known as apoB mRNA editing. A cDNA
      encoding the hamster apoB mRNA editing enzyme was obtained by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and the deduced amino acid
      sequence was found to possess high amino acid sequence identity to apoB mRNA
      editing enzymes from several other species. Editing activity was detected in the
      small intestine and colon but, like humans, none was detected in the liver.
      Analysis by RT-PCR indicated that the small intestine possessed the highest
      expression of editing enzyme mRNA abundance, whereas both liver and small
      intestine expressed relatively high levels of apoB mRNA. The influence of dietary
      zinc on intestinal apoB mRNA editing levels was examined in Golden Syrian
      hamsters (7 wk old) assigned to one of the following three dietary treatments: Zn
      adequate (ZA, 30 mg Zn/kg diet), Zn-deficient (ZD, <0. 5 mg Zn/kg diet), or Zn
      replenished (ZDA, ZD hamsters receiving ZA diet for last 2 d) for 7 wk. Hamsters
      consuming the ZD diet had modestly but significantly lower intestinal editing
      activity than ZA hamsters. Intestinal editing activity in the ZDA group was not
      different from that of ZA hamsters. Data derived from these studies contribute to
      the understanding of lipoprotein metabolism in hamsters, a suitable model for the
      study of atherosclerosis.

PMID- 10958810
TI  - Metallothionein mRNA in monocytes and peripheral blood mononuclear cells and in
      cells from dried blood spots increases after zinc supplementation of men.
AB  - A specific, sensitive and reliable index for assessment of human zinc status has
      not been developed, and continues to present a considerable challenge for
      nutritionists in the trace element field. We have focused on metallothionein (MT)
      expression as a potential index. A protocol involving 16 men and a 10-d
      supplementation period plus a 4-d postsupplementation period was used to examine
      the relative response of MT expression in erythrocytes, monocytes, peripheral
      blood mononuclear cells (PBMC) and cells from a dried blood spot (DBS). Zinc was
      supplemented at the current adult male recommended dietary allowance (RDA) of 15
      mg. Erythrocyte MT protein, as measured by ELISA, increased gradually to about
      twofold over the placebo group during zinc supplementation and remained elevated
      for 4 d postsupplementation. Competitive reverse transcriptase-polymerase chain
      reaction showed that MT mRNA levels in both monocytes and PBMC increased (up to
      4.7- and 2.7-fold, respectively) after 2 d of supplementation, with greater
      expression in monocytes compared with PBMC. Total RNA extracted from dried blood
      spots, representing cells from 50 microL of blood, showed a comparable change in
      MT mRNA upon zinc supplementation. In each leukocyte population isolated, when
      zinc supplementation was withdrawn, MT mRNA levels decreased. Collectively, these
      experiments show that, in men, MT gene expression increases during
      supplementation at the RDA, and that the DBS sampling method will be of value in
      measuring MT expression in a variety of clinical and survey situations.

PMID- 10958811
TI  - Body composition in human infants at birth and postnatally.
AB  - The predictive values of anthropometric measurements, race, gender, gestational
      and postnatal ages, and season at birth and at study for the total body dual
      energy X-ray absorptiometry (DXA)-derived lean mass (LM), fat mass (FM) and fat
      mass as a percentage of body weight (%FM) were determined in 214 singleton
      appropriate birth weight for gestational age infants [101 Caucasian (60 boys, 41
      girls) and 113 African American (55 boys, 58 girls)]. Gestational ages were 27-42
      wk and the infants were studied between birth and 391 d, weighing between 851 and
      13446 g. In addition, predictive value of body weight, LM and FM for DXA bone
      measurements was also determined. Scan acquisition used Hologic QDR 1000/W
      densitometer and infant platform and scans without significant movement artifacts
      were analyzed using software 5.64p. Body weight, length, gender and postnatal age
      were significant predictors of LM (adjusted R:(2) >0. 94) and FM (adjusted R:(2)
      >0.85). Physiologic variables had little predictive value for %FM except in the
      newborns (adjusted R:(2) 0. 69). Body weight was the dominant predictor of LM and
      FM, although length had similar predictive value for LM with increasing postnatal
      age. Female infants had less LM and more FM throughout infancy (P: < 0.01). LM or
      FM offered no advantage over body weight in the prediction of bone mass
      measurements. DXA is a useful means with which to determine body composition, and
      our data are important in the design and assessment of nutritional intervention
      studies.

PMID- 10958812
TI  - Iron bioavailability in humans from breakfasts enriched with iron bis-glycine
      chelate, phytates and polyphenols.
AB  - This study was conducted to determine the bioavailability of iron amino acid
      chelate (ferrochel) added to fortify breads prepared from either precooked corn
      flour or white wheat flour + cheese and margarine compared with the same basal
      breakfast enriched with either ferrous sulfate or iron-EDTA. The inhibitory
      effect of phytate and polyphenols on iron absorption from ferrochel was also
      tested. A total of 74 subjects were studied in five experiments. Iron absorption
      from ferrochel was about twice the absorption from ferrous sulfate (P: < 0.05).
      When ferrous sulfate and ferrochel were administered together or in different
      meals, absorption from ferrochel was about twice the absorption from ferrous
      sulfate (P: < 0.05). Polyphenols present in coffee and tea inhibited iron
      absorption in a dose-dependent manner. American-type coffee did not modify iron
      absorption significantly, whereas both espresso-type coffee and tea reduced iron
      absorption from ferrochel by 50% (P: < 0. 05). Ferrochel partially prevented the
      inhibitory effect of phytates. Because of its high solubility in aqueous
      solutions even at pH 6, its low interactions with food and high absorption,
      ferrochel is a suitable compound for food fortification.

PMID- 10958813
TI  - Moderate intervention with carotenoid-rich vegetable products reduces lipid
      peroxidation in men.
AB  - Because of their antioxidant properties, carotenoids may have beneficial effects
      in preventing cancer and cardiovascular disease. However, in humans consuming
      carotenoid-rich vegetables, data concerning the antioxidant effects of
      carotenoids are rather scarce. A human intervention trial was conducted,
      therefore, to determine whether a moderately increased consumption of carotenoid
      rich vegetables would influence the antioxidant status in 23 healthy men. This
      short-term feeding study lasted 8 wk during which the men consumed a low
      carotenoid diet. A 2-wk low carotenoid period was followed by daily consumption
      of 330 mL tomato juice, then by 330 mL carrot juice and then by 10 g of spinach
      powder, each for 2 wk. Antioxidant status [water-soluble antioxidants in serum,
      ferric reducing ability of plasma (FRAP) and antioxidant enzyme activities] and
      lipid peroxidation (plasma malondialdehyde and ex vivo oxidation of LDL) were
      determined. In a subgroup of 10 men, lipoprotein carotenoids were measured. The
      consumption of carotenoid-rich vegetables significantly increased selected
      carotenoids in lipoproteins but had only minor effects on their relative
      distribution pattern. Tomato juice consumption reduced plasma thiobarbituric acid
      reactive substances (TBARS) by 12% (P: < 0.05) and lipoprotein oxidizability in
      terms of an increased lag time (18%, P: < 0.05). Carrot juice and spinach powder
      had no effect on lipid peroxidation. Water-soluble antioxidants, FRAP,
      glutathione peroxidase and reductase activities did not change during any study
      period. In evaluating the low carotenoid diet, we conclude that the additional
      consumption of carotenoid-rich vegetable products enhanced lipoprotein carotenoid
      concentrations, but only tomato juice reduced LDL oxidation in healthy men.

PMID- 10958814
TI  - An examination of the possibility of lowering the glycemic index of oat and
      barley flakes by minimal processing.
AB  - Differences in glycemic responses to various starchy foods are related to
      differences in the rate of starch digestion and absorption. In this study, the
      importance of the degree of gelatinization and the product thickness for
      postprandial glycemic and insulinemic responses to rolled oats and barley were
      studied in healthy subjects (5 men and 5 women). Thick (1.0 mm) rolled oats were
      made from raw or preheated (roasted or steamed) kernels. In addition, thin (0.5
      mm) rolled oats were made from roasted or roasted and steamed (processed under
      conditions simulating commercial production) oat kernels. Finally, steamed rolled
      barley kernels (0.5 or 1.0 mm) were prepared. All thin flakes elicited high
      glucose and insulin responses [glycemic index (GI), 88-118; insulinemic index
      (II), 84-102], not significantly different from white wheat bread (P: > 0.05). In
      contrast, all varieties of thick oat flakes gave significantly lower metabolic
      responses (GI, 70-78; II, 58-77) than the reference bread (P: < 0.05). Thick
      barley flakes, however, gave high glucose and insulin responses (GI, 94; II, 84),
      probably because the botanical structure underwent more destruction than the
      corresponding oat flakes. We conclude that minimal processing of oat and barley
      flakes had a relatively minor effect on GI features compared with the more
      extensive commercial processing. One exception was thick oat flakes, which in
      contrast to the corresponding barley flakes, had a low GI.

PMID- 10958815
TI  - Rye bread improves bowel function and decreases the concentrations of some
      compounds that are putative colon cancer risk markers in middle-aged women and
      men.
AB  - Cereal fiber may reduce the risk of colorectal cancer by diluting colonic
      contents due to increased fecal output, by accelerating intestinal transit, by
      increasing fecal frequency and by altering bacterial metabolism. The effects of
      whole-meal rye bread on some putative colon cancer risk markers were investigated
      in 17 healthy Finnish subjects using a randomized crossover trial with two 4-wk
      bread consumption periods and a 4-wk washout period between the bread periods.
      White wheat bread was used as a control. Test breads covered a minimum of 20% of
      the daily energy intake (range, 4330-14, 033 kJ/d). Intestinal transit time,
      stool weight, fecal bacterial enzyme activities and short-chain fatty acid,
      ammonia, diacylglycerol (DAG) and bile acid concentrations in feces (expressed
      per gram wet feces) were measured. Whole-meal rye bread significantly increased
      fecal output and fecal frequency and shortened mean intestinal transit time
      compared with wheat bread in both women and men. Activities of beta-glucuronidase
      and beta-glucosidase (expressed per gram wet feces) were significantly lower in
      men and urease activity significantly higher in women during the rye bread period
      (RBP). Fecal butyrate concentration was higher during the RBP in men. Fecal
      ammonia and DAG concentrations did not differ between bread periods. Fecal total
      and secondary bile acid concentrations were significantly lower during RBP in
      both women and men. This study shows that whole-meal rye bread significantly
      improves bowel function in healthy adults and may decrease the concentration of
      some compounds that are putative colon cancer risk markers.

PMID- 10958816
TI  - The relationship between plasma taurine and other amino acid levels in human
      sepsis.
AB  - Although reports of decreased plasma taurine in trauma, sepsis and critical
      illness are available, very little is known about the relationships among changes
      in plasma taurine, other amino acid levels and metabolic variables. We analyzed a
      large series of plasma amino acid profiles obtained in trauma patients with
      sepsis who were undergoing total parenteral nutrition. The correlations between
      plasma taurine, other amino acid levels, parenteral substrate doses and metabolic
      and cardiorespiratory variables were assessed by regression analysis. Post
      traumatic hypotaurinemia was followed by partial recovery toward less abnormal
      values when sepsis developed. Levels of taurine were directly and significantly
      related to levels of glutamate, aspartate, beta-alanine and phosphoethanolamine
      (and unrelated to other amino acids). Levels of these amino acids increased
      simultaneously with increasing doses of leucine, isoleucine and valine in total
      parenteral nutrition. Decreasing taurine was associated with increasing lactate,
      arteriovenous O(2) concentration difference and respiratory index, and with
      decreasing cholesterol and cardiac index. These results characterize the
      relationships between plasma taurine and other amino acid levels in sepsis,
      provide evidence of amino acid interactions that may support taurine availability
      and show more severe decreases in plasma taurine with the worsening of metabolic
      and cardiorespiratory patterns.

PMID- 10958817
TI  - Lowering dietary saturated fat and total fat reduces the oxidative susceptibility
      of LDL in healthy men and women.
AB  - The present study examined the effects of reducing dietary total fat and
      saturated fat (SFA) on LDL oxidative susceptibility in 27 healthy men and women
      (age 24-65 y). Each subject consumed each of three diets for 8 wk: an average
      American diet (AAD, 34% energy from fat, 15% from SFA), a Step-1 diet (29% fat,
      9% SFA) and a very low SFA diet (Low-Sat, 25% fat, 6% SFA). In vitro LDL
      oxidation was assessed by copper-mediated oxidation, as measured by the kinetics
      of conjugated diene formation and lipid peroxide formation. Compared with the
      AAD, plasma LDL-cholesterol (LDL-C) and HDL cholesterol levels were 8% lower (P:
      = 0.16 and P: = 0.11, respectively), in subjects when they consumed the Step-1
      diet and 11% (P: < 0.03) and 14% (P: < 0.057) lower, respectively, when they
      consumed the Low-Sat diet. Conjugated diene production and oxidation rate were 7%
      (P: < 0. 05) and 9% (P: < 0.05) lower, respectively. The reduction of lipid
      peroxide formation was 9% (P: < 0.05) in subjects when they consumed the Low-Sat
      diet vs. the AAD. In addition, lipid peroxide and conjugated diene formation were
      positively correlated with plasma total and LDL-C and apolipoprotein B (apo B)
      levels (r = 0.5-0.6, P: < 0.001), suggesting that quantity of LDL is an important
      determinant of oxidative modification. Furthermore, at the same level of apo B or
      LDL-C, LDL from subjects when they consumed either Step-1 or Low-Sat diets was
      less susceptible (P: < 0.05) to oxidation than those when they consumed the AAD,
      suggesting that qualitative changes also affect LDL oxidative susceptibility.
      Therefore, the benefits of lowering dietary SFA may extend beyond decreasing LDL
      C levels and include favorable qualitative changes in LDL that further decrease
      risk of coronary heart disease.

PMID- 10958818
TI  - Conversion of 5-formyltetrahydrofolic acid to 5-methyltetrahydrofolic acid is
      unimpaired in folate-adequate persons homozygous for the C677T mutation in the
      methylenetetrahydrofolate reductase gene.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5
      methyltetrahydrofolic acid (5-CH(3)-H(4) folic acid), the methyl donor for the
      formation of methionine from homocysteine. A common C677T transition in the MTHFR
      gene results in a variant with a lower specific activity and a greater
      sensitivity to heat than the normal enzyme, as measured in vitro. This study was
      undertaken to determine the capacity of homozygotes for the MTHFR C677T
      transition to convert 5-formyltetrahydrofolic acid (5-HCO-H(4) folic acid) to 5
      CH(3)-H(4) folic acid, a process that requires the action of MTHFR. Six subjects
      homozygous for the C677T transition (T/T) and 6 subjects with wild-type MTHFR
      (C/C) were given a 5-mg oral dose of (6R:,S:)-5-HCO-H(4) folic acid. Plasma and
      urine were analyzed for 5-CH(3)-H(4) folic acid concentrations using
      affinity/HPLC coupled with fluorescence or UV detection. The mean areas under the
      curves created by the rise and fall of plasma 5-CH(3)-H(4) folic acid after the
      oral dose did not differ between the two genotypes, 424.5 +/- 140.3 (T/T) vs.
      424.1+/- 202.4 h.nmol/L (C/C). There also was no significant difference in the
      mean cumulative 7-h urinary excretion of 5-CH(3)-H(4) folic acid between the T/T
      (2.5 +/- 1.4 micromol) and C/C (1.9 +/- 1.0 micromol) genotypes. Under the
      conditions employed, the conversion of oral 5-HCO-H(4) folic acid to 5-CH(3)-H(4)
      folic acid is not impaired in persons with the T/T MTHFR genotype. Possible
      reasons for these findings are discussed.

PMID- 10958819
TI  - Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the
      inverse correlation between quercetin intake and plasma LDL cholesterol
      concentration.
AB  - The intake of flavonols, flavones and isoflavones by Japanese women was
      calculated from our food-phytochemical composition table. The relationship
      between intake of these phytochemicals and various anthropometric and blood
      chemistry data was analyzed in a cross-sectional study. The subjects were 115
      women volunteers, aged 29-78 y, living in the northern part of Japan. Each
      subject completed a 3-d dietary record and received a health check up, including
      urine and blood sampling for biochemical analysis. Total mean intakes of
      flavonoids (sum of flavonols and flavones) and isoflavones were 16.7 and 47.2
      mg/d, respectively. The major source of flavonoids was onions (45.9%) and that of
      isoflavones was tofu (37.0%). Total intake of isoflavones exceeded that of other
      dietary antioxidants, such as flavonoids, carotenoids (3.5 mg/d) and vitamin E
      (8.2 mg/d), and was approximately one half of the vitamin C intake (109 mg/d).
      The total intake of flavonoids was inversely correlated with the plasma total
      cholesterol concentration (TC) (r = -0.236, P: < 0.05) and plasma LDL cholesterol
      concentration (LDL-C) (r = -0.220, P: < 0.05), after the adjustment for age, body
      mass index and total energy intake. As a single component, quercetin was
      inversely correlated with both TC (r = -0.261, P: < 0.01) and LDL-C (r = -0. 263,
      P: < 0.01). Among Japanese, flavonoid and isoflavone intake is the main component
      among nonnutrient phytochemicals with antioxidant potential in the diet. These
      results suggest that a high consumption of both flavonoids and isoflavones by
      Japanese women may contribute to their low incidence of coronary heart disease
      compared with women in other countries.

PMID- 10958820
TI  - Prenatal iron supplements impair zinc absorption in pregnant Peruvian women.
AB  - Prenatal iron supplements may adversely influence zinc absorption during
      pregnancy. To examine the impact of prenatal iron supplements on supplemental
      zinc absorption, fractional zinc absorption was measured in 47 pregnant Peruvian
      women during the third trimester of pregnancy (33 +/- 1 wk gestation). Of these
      47 women, 30 received daily prenatal supplements from wk 10-24 of pregnancy until
      delivery. Supplements contained 60 mg of Fe and 250 microg of folate without
      [iron group (Fe), n = 16] or with [iron and zinc supplemented group (Fe + Zn), n
      = 14] 15 mg of Zn. The remaining 17 women [unsupplemented control group (C)]
      received no prenatal supplementation. Zinc concentrations were measured in
      plasma, urine and cord blood and percentage zinc absorption was determined
      following dosing with oral ((67)Zn) and intravenous ((70)Zn) stable zinc
      isotopes. Percentage zinc absorption was significantly lower than controls in
      fasting women receiving iron- containing prenatal supplements (20.5 +/- 6.4 vs.
      20.2 +/- 4.6 vs. 47.0 +/- 12.6%, Fe, Fe + Zn and C groups, respectively, P: <
      0.0001, n = 40). Plasma zinc concentrations were also significantly lower in the
      Fe group compared to the C group (8.2 +/- 2.2 vs. 9.2 +/- 2.2 vs. 10.9 +/- 1. 8
      micromol/L, Fe, Fe + Zn and C groups, respectively, P: = 0.002), and cord zinc
      concentrations were significantly related to maternal plasma Zn levels (y = 6.383
      + 0.555x, r = 0.486, P: = 0.002). The inclusion of zinc in prenatal supplements
      may reduce the potential for iron supplements to adversely influence zinc status
      in populations at risk for deficiency of both these nutrients.

PMID- 10958821
TI  - Living arrangements affect dietary quality for U.S. adults aged 50 years and
      older: NHANES III 1988-1994.
AB  - The number and proportion of older U.S. adults who live alone have increased
      dramatically in the past three decades, and there is concern that these
      individuals may have particularly poor dietary quality. We examined the
      association of four living arrangements (living with a spouse only, with a spouse
      plus someone else, with someone other than a spouse or living alone) with dietary
      quality (the number of low nutrients out of a possible 15, with low defined as
      <67% of the recommended dietary allowance) among 6525 U.S. adults aged 50-64 y
      and those >/=65 y in the third National Health and Nutrition Examination Survey
      (NHANES III 1988-1994). Among non-Hispanic Caucasian adults, those who lived with
      a spouse only had better dietary quality, with significant differences ranging
      from 0.8 to 1.5 fewer low nutrients compared with those with other living
      arrangements. Effects of living arrangements on dietary quality were also seen
      among non-Hispanic African-Americans, Mexican-Americans, and those of "other"
      races, but differences were significant only for African-American men aged >65 y
      living with a spouse plus others (1.6 additional low nutrients compared with
      those living with a spouse only). Energy intake was strongly associated with
      dietary quality, but did not account for the associations between living
      arrangements and dietary quality. Although middle-aged and older adults with
      living arrangements other than living with a spouse only (including those living
      alone) tended to have poorer dietary quality, the effects varied substantially
      across age, gender and ethnic categories.

PMID- 10958822
TI  - Regulation of energy intake may be impaired in nutritionally stunted children
      from the shantytowns of Sao Paulo, Brazil.
AB  - We tested the hypothesis that nutritionally stunted children have impaired
      regulation of energy intake (EI), a factor that could help explain the increased
      risk of obesity associated with stunting in developing countries. A 3-d residency
      study was conducted in 56 prepubertal boys and girls aged 8-11 y from the
      shantytowns of Sao Paulo, Brazil. Twenty-seven of the subjects were stunted and
      29 were not stunted; weight-for-height Z-scores were not significantly different
      between the groups. Parents of the two groups had equivalent heights and body
      mass indices. Measurements were made of voluntary EI from a self-selection menu,
      resting energy expenditure (REE) and body composition. In addition, a 753-kJ
      yogurt supplement was administered at breakfast on one study day (with an equal
      number of children receiving the supplement on each of the 3 study days) and its
      effect on daily EI assessed. There was no change in EI over time in either group
      (P: = 0.957), and no significant difference in EI between stunted and nonstunted
      children, even though the stunted children weighed 10% less. Energy intake per
      kilogram body weight was significantly higher in the stunted children (278 +/- 89
      (SD), vs. 333 +/- 67 kJ/kg, P: < 0.05) and EI/REE was also significantly higher
      (1.91 +/- 0.34 vs. 1.68 +/- 0.38, P: < 0.05). However, the relationship between
      EI and body weight was not significantly influenced by stunting (P: = 0.12).
      There was no significant effect of the breakfast supplement on daily EI in either
      group although the absolute difference in EI between supplement and control days
      was greater in stunted than in nonstunted children (DeltaEI: +460 +/- 1574 vs. 
      103 +/- 1916 kJ/d, P: = 0.25). These data provide preliminary evidence consistent
      with the suggestion that stunted children tend to overeat opportunistically, but
      further studies are required to confirm these results in a larger study.

PMID- 10958823
TI  - Co-occurrence of nutrition problems in Honduran children.
AB  - We used data from the 1996 Honduras National Micronutrient Survey to investigate
      the co-occurrence of vitamin A deficiency (VAD), anemia and stunting in a
      representative sample of Honduran children 1-5 y old. Observed frequencies of co
      occurrence were compared with frequencies expected by chance in children 12-35.9
      mo old (n = 633) and 36-59.9 mo old (n = 610) for the three possible two-way
      combinations of the problems and the three-way combination. Observed frequencies
      were greater than expected frequencies for all eight comparisons, and all
      comparisons except for that of stunting and anemia in younger children were
      significant. The observed frequency of the three-way co-occurrence was 8.4%
      compared with an expected co-occurrence of 8.1% in younger children (P: < 0.05)
      and 4.8% compared with 4.2%, respectively, in older children (P: < 0.001).
      Although there was statistical evidence for co-occurrence, differences between
      expected and observed prevalences were small for most comparisons. Our findings
      suggest that having one or two problems does not appreciably increase the
      probability of having another. The efficiency of nutrition interventions aimed at
      these conditions would not be improved by targeting children with any one of the
      conditions; rather, the three conditions should be treated as virtually
      independent when designing programs. Replication of this study in other settings
      is warranted.

PMID- 10958825
TI  - Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by
      Delta(9)-desaturase.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring anticarcinogen found in
      milk fat and body fat of ruminants. Although CLA is an intermediate in ruminal
      biohydrogenation of linoleic acid, we hypothesized that its primary source was
      from endogenous synthesis. This would involve Delta(9)-desaturase and synthesis
      from trans-11 18:1, another intermediate in ruminal biohydrogenation. Our first
      experiment supplied lactating cows (n = 3) with trans-11 18:1 by abomasal
      infusion and examined the potential for endogenous synthesis by measuring changes
      in milk fat CLA. By d 3, infusion of trans-11 18:1 resulted in a 31% increase in
      concentration of cis-9, trans-11 CLA in milk fat, demonstrating that an active
      pathway for endogenous synthesis of CLA exists. Our second experiment examined
      the quantitative importance of endogenous synthesis of CLA in lactating cows (n =
      3) by abomasally infusing a putative stimulator (retinol palmitate) or an
      inhibitor (sterculic oil) of Delta(9)-desaturase. Infusion of retinol palmitate
      had no influence on milk fatty acid desaturation, and yield of CLA in milk fat
      was not altered. However, sterculic oil infusion decreased the concentration of
      CLA in milk fat by 45%. Consistent with Delta(9)-desaturase inhibition, the
      sterculic oil treatment also altered the milk fat concentration of other Delta(9)
      desaturase products as indicated by the two- to threefold increase in the ratios
      of 14:0 to 14:1(,) 16:0 to 16:1 and 18:0 to cis-18:1. Using changes in the ratio
      of 14:0 to 14:1 as an indication of the extent of Delta(9)-desaturase inhibition
      with the sterculic oil treatment, an estimated 64% of the CLA in milk fat was of
      endogenous origin. Overall, results demonstrate that endogenous synthesis of CLA
      from trans-11 18:1 represented the primary source of CLA in milk fat of lactating
      cows.

PMID- 10958824
TI  - Dietary ratio of (n-6)/(n-3) polyunsaturated fatty acids alters the fatty acid
      composition of bone compartments and biomarkers of bone formation in rats.
AB  - The effects of dietary polyunsaturated fatty acids (PUFA) on ex vivo bone
      prostaglandin E(2) (PGE(2)) production and bone formation rate were evaluated in
      rats. Weanling male Sprague-Dawley rats were fed AIN-93G diet containing 70 g/kg
      of added fat for 42 d. The dietary lipid treatments were formulated with
      safflower oil and menhaden oil to provide the following ratios of (n-6)/(n-3)
      fatty acids: 23.8 (SMI), 9.8 (SMII), 2.6 (SMIII), and 1.2 (SMIV). Ex vivo PGE(2)
      production in liver homogenates and bone organ cultures (right femur and tibia)
      were significantly lower in rats fed diets with a lower dietary ratio of (n-6)/(n
      3) fatty acids than in those fed diets with a higher dietary ratio. Regression
      analysis revealed a significant positive correlation between bone PGE(2) and the
      ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA), but significant
      negative correlations between bone formation rate and either the ratio of AA/EPA
      or PGE(2) in bone. Activities of serum alkaline phosphatase isoenzymes, including
      the bone-specific isoenzyme (BALP), were greater in rats fed a diet high in (n-3)
      or a low ratio of (n-6)/(n-3), further supporting the positive action of (n-3)
      fatty acids on bone formation. These results demonstrated that the dietary ratio
      of (n-6)/(n-3) modulates bone PGE(2) production and the activity of serum BALP in
      growing rats.

PMID- 10958826
TI  - Dietary conjugated linoleic acids alter adipose tissue and milk lipids of
      pregnant and lactating sows.
AB  - Conjugated linoleic acids (CLA) have been shown to affect fatty acid synthesis in
      various tissues. The objective of the study was to compare the effect of a
      commercial source of CLA with a linoleic acid-enriched oil (LA), supplied to 12
      multiparous sows during gestation and lactation, on adipose tissue and milk fatty
      acid composition. The CLA isomers detected in the CLA oil were (in order of
      magnitude) c9,t11; t10,c12; c9,c11; t9,t11/t10,t12 and c10,c12 and amounted to
      58.9 g/100 g fat. Biopsies were taken from the backfat on d 7 and 97 of gestation
      and milk samples were collected on d 2, 9, 16 and 23 after farrowing. Collection
      of colostrum and mature milk samples took place at 1100 h for sows who farrowed
      in the morning or at 1500 h for those who farrowed in the afternoon. All major
      CLA isomers in the supplement were transferred to the tissue and milk fat and,
      compared with the LA group, significantly increased saturated fatty acid and
      decreased monounsaturated fatty acid levels in the tissue and milk. These
      findings suggest a distinct involvement of CLA in the de novo fatty acid
      synthesis and desaturation process in the adipose tissue and mammary gland.
      Estimated transfer efficiency of dietary CLA isomers was 41-52% for the backfat
      and 55-69% for the mature milk. The incorporation and uptake efficiency seemed to
      be selective with the highest values found for c9,t11-CLA. Overall, dietary CLA
      supplementation of sows during gestation and lactation markedly altered backfat
      and milk fatty acid composition.

PMID- 10958828
TI  - Exchangeable magnesium pool masses reflect the magnesium status of rats.
AB  - A sensitive and valid marker to assess magnesium (Mg) status in humans is not
      available. The kinetically determined exchangeable pool masses have been used for
      other minerals, such as zinc and selenium, as markers of whole-body mineral
      status. To evaluate the validity of this relationship for Mg, we measured the
      exchangeable pools of Mg in rats over a range of magnesium dietary intakes. Rats
      weighing approximately 170 g were fed a control diet (500 mg Mg/kg), a marginally
      Mg-deficient diet (200 mg/kg) or a severely Mg-deficient diet (60 mg Mg/kg) for 2
      wk. Subsequently, rats were administered an intravenous injection of (25)Mg, and
      the plasma (25)Mg disappearance curve was followed for the next 7 d. The
      following two methods were employed to analyze the exchangeable pools of Mg: 1)
      formal compartmental modeling and 2) a simplified determination of the total mass
      of the rapidly exchangeable Mg pool (EMgP). The mass of the three exchangeable
      pools (two extracellular pools and one intracellular pool) determined by
      compartmental analysis decreased in proportion to dietary Mg intake. EMgP, the
      combined pools of Mg that exchange with the plasma Mg within 48 h, decreased
      significantly as dietary Mg was lowered. It was positively correlated with
      conventional markers of Mg status (total Mg in plasma, erythrocyte and tibia Mg
      levels). Compartmental analysis assesses Mg exchangeable pools more accurately,
      but determination of EMgP is simpler and faster. Our findings demonstrate that
      the exchangeable pools of Mg constitute a good marker of Mg status in rats.

PMID- 10958827
TI  - Urinary composition and postprandial blood changes in H-secoisolariciresinol
      diglycoside (SDG) metabolites in rats do not differ between acute and chronic SDG
      treatments.
AB  - Although chronic exposure to secoisolariciresinol diglycoside (SDG) was shown to
      alter (3)H-SDG metabolite disposition in rats, the proportion of measured
      radioactivity attributed to known or unknown SDG metabolites was not determined.
      Using HPLC and GC-MS, two experiments were conducted to determine the effect of
      acute (1 d) vs. chronic (10 d) SDG treatment on major urinary metabolites of (3)H
      SDG in female, Sprague-Dawley rats (70-72-d-old) over a 48-h period and if new
      urinary metabolites were detectable in rats fed nonradioactive flaxseed or SDG. A
      third experiment was conducted to determine changes in postprandial blood levels
      of (3)H-SDG metabolites over a 24-h period with acute or chronic SDG treatment.
      Regardless of treatment, enterodiol, enterolactone and secoisolariciresinol
      accounted for 75-80% of urine radioactivity. Four potential new lignan
      metabolites, two of which were detected in the urine of rats fed nonradioactive
      flaxseed or SDG, were found. Type of treatment had no effect on levels of
      individual urinary metabolites of (3)H-SDG. As observed for plasma lignans in
      women fed flaxseed, blood radioactivity peaked at 9 h and remained high until 24
      h in both treatment groups, suggesting that blood lignan kinetics might be
      similar with flaxseed or SDG consumption and that they were comparable between
      humans and rats. In conclusion, the main urinary lignan metabolites were
      enterodiol, enterolactone and secoisolariciresinol. Urinary composition or blood
      levels of radioactive lignans were not affected by the duration of SDG exposure.
      Thus, while chronic SDG exposure alters lignan disposition in rats, it does not
      change the metabolite profile.

PMID- 10958829
TI  - A high-protein meal exceeds anabolic and catabolic capacities in rats adapted to
      a normal protein diet.
AB  - The postprandial fixation of dietary nitrogen in splanchnic and peripheral
      tissues as well as its dynamic transfer to the nitrogen pools of the body were
      quantified in rats subjected to an acute augmentation of dietary protein. For
      this purpose, we traced the dietary protein and studied the immediate fate of
      exogenous nitrogen in many tissues and biological fluids. Rats were adapted to a
      diet providing an adequate protein level (14 g/100 g), and then fed a meal
      containing either 0.42 g (Group A) or 1.50 g (Group H) of [(15)N]-labeled milk
      protein. The amounts of exogenous nitrogen transferred to urea (0.32 +/- 0.04 vs.
      2.46 +/- 0.25 mmol, respectively), incorporated in splanchnic (0.41 +/- 0.02 vs.
      0.87 +/- 0.10 mmol) and peripheral (1.65 +/- 0.84 vs. 2.36 +/- 0.49 mmol) tissue
      protein were higher in group H than in group A. Individual plasma amino acids
      (AA) [(15)N]-enrichments showed that AA respond differentially to an acute
      augmentation of dietary intake. This work provides new descriptive and
      quantitative information on the metabolic fate of dietary nitrogen in the
      postprandial state. It highlights the higher integration of a surplus of dietary
      nitrogen in the tissues even if it is rapidly limited by saturation of the
      protein synthesis capacities. The main metabolic response remains the stimulation
      of AA degradation, leading to a large rise in urea production. However, both
      anabolic and catabolic systems are exceeded, resulting in an elevation of
      peripheral AA and negative feedback on the gastric emptying rate.

PMID- 10958830
TI  - Dietary beta-carotene absorption by blood plasma and leukocytes in domestic cats.
AB  - Three experiments were conducted to study the uptake of oral beta-carotene by
      blood plasma and leukocytes in domestic cats. In Experiment 1, mature female
      Tabby cats (12 mo old) were given once orally 0, 10, 20 or 50 mg of beta-carotene
      and blood taken at 0, 12, 24, 30, 36, 42, 48 and 72 h after dosing.
      Concentrations of plasma beta-carotene increased in a dose-dependent manner. Peak
      concentrations were observed at 12-24 h and declined gradually thereafter. The
      half-life of plasma beta-carotene was 12-30 h. In Experiment 2, cats were dosed
      daily for six consecutive days with 0, 1, 2, 5 or 10 mg beta-carotene. Blood was
      sampled once daily at 12 h after each feeding. Daily dosing of cats with beta
      carotene for 6 d resulted in a dose-dependent increase in circulating beta
      carotene. Experiment 3 was designed to study the uptake of beta-carotene by blood
      leukocytes. Cats were fed 0, 5 or 10 mg of beta-carotene daily for 14 d. Blood
      leukocytes were obtained on d 7 and 14 to determine beta-carotene content in
      whole lymphocytes and in subcellular fractions. Blood lymphocytes took up large
      amounts of beta-carotene by d 7 of feeding. Furthermore, beta-carotene
      accumulated mainly in the mitochondria (40-52%), with lower amounts accumulating
      in the microsomes (20-35%), cytosol (15-34%), and nuclei (1.5-6%). Therefore,
      domestic cats readily absorb beta-carotene across the intestinal mucosa and
      transfer the beta-carotene into peripheral blood leukocytes and their subcellular
      organelles. beta-Carotene uptake kinetics show that some aspects of beta-carotene
      absorption and metabolism in cats are similar to those of humans.

PMID- 10958831
TI  - Bones, muscles and visceral organs of protein-malnourished rats (Rattus
      norvegicus) grow more slowly but for longer durations to reach normal final size.
AB  - Starting at weaning (22 d), Sprague-Dawley rats were fed either a control diet
      high in protein (CT, 24% protein) or an isocaloric low protein diet (LPT, 4%
      protein) to determine how protein malnutrition alters the rate and timing of limb
      bone growth. Length and width measurements were taken from longitudinal
      radiographs to provide complete growth trajectories of both treatments. Data
      collection continued until rats reached adult size, which varied among diet-sex
      groups. The rats were then killed and five muscles and eight organs were weighed.
      A nonlinear Gompertz model was then fit to each trajectory for 13 skeletal
      measurements, producing parameters that described the rate and timing of growth
      for each rat, the unit of analysis. Parameter differences due to diet, sex and
      litter were tested by using a mixed-model, three-way ANOVA. For most
      measurements, the LPT rats were not significantly smaller than the CT rats, for
      the model's prediction of final size. Bone length was significantly less affected
      than width. The instantaneous initial growth rate, maximum rate of growth and
      rate of growth decay were significantly higher in the control rats for all
      measurements. The rats fed the low protein diet grew for significantly longer
      periods of time. For all muscles and most organs relative to body size, there was
      no difference between rats fed the two diets. The exceptions, eyes and brains,
      were proportionally larger in the LPT rats, suggesting that these organs receive
      nutritional priority during growth. For the systems in this study, structures
      that grow or have the potential for extended growth are less affected by the
      nutritional insult.

PMID- 10958832
TI  - A cooperative interaction between soy protein and its isoflavone-enriched
      fraction lowers hepatic lipids in male obese Zucker rats and reduces blood
      platelet sensitivity in male Sprague-Dawley rats.
AB  - Soy protein diets lower plasma cholesterol in hyperlipoproteinemic human
      subjects, as well as in animal models. We fed 7-wk-old male obese (fa/fa) and
      lean Zucker rats a modified AIN-76 diet (20 g protein/kg diet) containing casein
      (C), low isoflavone soy protein (38 mg isoflavones/kg diet; LI), or high
      isoflavone soy protein (578 mg isoflavones/kg diet; HI) for 70 d. In obese rats,
      plasma total cholesterol was 21 and 29% lower in the LI and HI groups,
      respectively, than in the C group (P: </= 0.004). Liver weight and liver
      triglyceride and cholesteryl ester concentrations were 27, 33 and 46% lower,
      respectively, in the LI group than in the C group (P: < 0.003). These liver
      measurements were 23, 24 and 57% lower, respectively, in the HI group than in the
      LI group (P: < 0.05). In a complementary study, 5-wk-old male Sprague-Dawley rats
      were fed the same C, LI and HI diets for 42 d. Thrombin-mediated platelet
      serotonin release in vitro was 13% lower in the HI group than in the C group (P:
      = 0.003). In a third study, 7-wk-old male Sprague-Dawley rats were fed either a
      modified AIN-76 control diet or a high fat casein-based atherogenic diet (140 g
      fat, 12 g cholesterol, and 2 g cholic acid/kg diet) with or without a soy
      isoflavones extract (983 mg isoflavones/kg diet) for 63 d. Addition of the
      isoflavones extract to the atherogenic diet lowered the liver triglyceride
      concentration by 33% relative to the atherogenic diet without isoflavones (P: =
      0.0001). Our studies suggest that the hypocholesterolemic mechanism of dietary
      soy protein involves a cooperative interaction between the protein and isoflavone
      enriched fraction that lowers hepatic lipid concentrations. We speculate that
      modulation of liver and plasma lipid homeostasis can also lower blood platelet
      sensitivity.

PMID- 10958834
TI  - Long-term consumption of a methionine-supplemented diet increases iron and lipid
      peroxide levels in rat liver.
AB  - Methionine is a protective factor against various types of liver damage, but
      excessive dietary methionine is hepatotoxic. Because the mechanisms of L
      methionine-related hepatotoxicity are poorly understood, the effect of long-term
      excessive L-methionine intake on the metabolism of iron and antioxidants was
      studied in rat liver to determine whether oxidative stress is involved. Wistar
      male rats were fed either an L-methionine-supplemented (16.0 g/kg) diet or a
      control diet for 1, 3, 6 and 9 mo. The growth rate of L-methionine-supplemented
      rats was significantly slower than that of controls. Iron, ferritin and
      thiobarbituric acid-reactive substances (TBARS) levels in the liver were greater
      in supplemented rats than in controls. Serum iron and transferrin levels were
      significantly lower in L-methionine-treated rats compared with controls. Serum
      ferritin did not differ between the two groups. Hepatic glutathione peroxidase
      activity, catalase activity and total glutathione concentrations were higher in
      rats fed the L-methionine-supplemented diet at 1 and 3 mo, but not at 6 and 9 mo.
      These results indicate that long-term consumption of excess L-methionine by rats
      may affect primarily iron metabolism rather than the antioxidant defense system
      and, consequently, induce an accumulation of iron.

PMID- 10958833
TI  - Dietary coenzyme Q10 and vitamin E alter the status of these compounds in rat
      tissues and mitochondria.
AB  - Vitamin E (VE) and coenzyme Q (CQ) are essential for maintaining functions and
      integrity of mitochondria, and high concentrations of these compounds are found
      in their inner membranes. This study was conducted to examine the interaction
      between exogenously administered CQ10 and VE in rats. Male Sprague-Dawley rats
      (12 mo old) were fed a basal diet (10 IU VE or 6.7 mg RRR-alpha-tocopherol
      equivalent) supplemented with either 0 or 500 mg CQ10, and 0, 100 or 1310 IU
      VE/kg diet for 14 or 28 d. Liver, spleen, heart, kidney, skeletal muscle, brain
      and serum were analyzed for the levels of CQ10, CQ9 and VE. CQ10 supplementation
      significantly (P: < 0.05) increased CQ10 concentration in the liver and spleen
      (total and mitochondria) and serum, but not in other organs. Interestingly, rats
      supplemented with CQ10 plus 100 IU VE/kg diet had significantly higher CQ10
      levels in the liver and spleen, whereas those supplemented with CQ10 plus 1310 IU
      VE/kg diet had lower levels, compared with those supplemented with CQ10 alone. As
      expected, dietary VE increased VE content in all of the organs analyzed in a dose
      dependent manner. However, rats fed the basal diet supplemented with CQ10 had
      significantly higher VE levels in liver (total and mitochondria) than those not
      receiving CQ10 supplementation. CQ9 levels were higher in the liver and spleen,
      lower in skeletal muscle and unaltered in brain, serum, heart and kidney of rats
      supplemented with CQ10 compared with the controls. These data provide direct
      evidence for an interactive effect between exogenously administered VE and CQ10
      in terms of tissue uptake and retention, and for a sparing effect of CQ10 on VE.
      Data also suggest that dietary VE plays a key role in determining tissue
      retention of exogenous CQ10.

PMID- 10958835
TI  - High dietary fat intake increases renal cyst disease progression in Han:SPRD-cy
      rats.
AB  - The effect of a high level of dietary fat on renal cyst disease was examined in
      the Han:SPRD-cy rat model of polycystic kidney disease. Control and diseased rats
      at 4 wk of age were fed either a low fat or high fat diet (5 or 20 g/100 g diet)
      for 6 wk. In rats with kidney disease fed the high fat rather than the low fat
      diet, kidneys were 17% larger, renal fluid content was 19% higher and cyst scores
      were 30% higher, indicating greater disease progression. In diseased rats fed the
      high fat diet, serum urea was 25% higher, indicating worsened renal function.
      Serum creatinine was 49% higher only in males. To examine whether high dietary
      fat worsened renal cyst disease by altering sex hormone concentrations, serum
      testosterone and estrogen concentrations were determined. In normal compared with
      diseased male rats, serum testosterone concentrations were one to three times
      higher. Serum testosterone concentrations were higher in normal male rats fed the
      high compared with the low fat diet, but were not affected by diet in diseased
      rats. Serum estrogen concentrations were unaffected by dietary fat levels or by
      disease state. Although it remains to be elucidated how dietary fat influences
      sex hormone concentrations in this disease, the current study demonstrates that a
      high dietary fat intake increases kidney disease progression in Han:SPRD-cy rats.

PMID- 10958836
TI  - Dietary fat alters HIV protease inhibitor-induced metabolic changes in mice.
AB  - Human immunodeficiency virus (HIV) protease inhibitors (PI) may alter lipid
      metabolism in patients with acquired immunodeficiency syndrome (AIDS). However,
      the influence of dietary fat on the metabolic effects of PI therapy remains
      unknown. AKR/J mice were fed high or low fat diets and treated with the PI
      indinavir (IDV), nelfinavir (NFV), saquinavir (SQV) or amprenavir (APV) by
      subcutaneous delivery for 2 wk. Serum concentrations of glucose, insulin,
      triglyceride, free fatty acid, glycerol, pancreatic lipase, bilirubin, alkaline
      phosphatase, blood urea nitrogen and PI, and interscapular and epididymal fat
      weights were determined. Some metabolic effects of PI were dependent on diet. IDV
      and NFV-treated mice had greater serum glucose concentration and body weight;
      IDV-treated mice had lower serum insulin; NFV-treated mice had greater
      interscapular fat mass; and SQV treated mice had lower serum triglyceride
      concentration than control mice fed the low but not the high fat diet. In
      contrast, NFV- and IDV-treated mice had greater triglyceride concentration and
      blood urea nitrogen, and SQV treated mice had greater serum cholesterol than
      control mice fed the high but not the low fat diet. The serum concentration of
      SQV was lower in mice fed the high fat compared with the low fat diet. Other
      effects were not dependent on diet. IDV- and NFV-treated mice had greater fatty
      acids, and IDV-treated mice had greater pancreatic lipase, bilirubin and alkaline
      phosphatase than control mice fed either diet. APV treatment had little effect on
      these serum measurements. Thus, changes in dietary fat can influence some but not
      all of the effects of PI on metabolism. Furthermore, each PI produces different
      effects in vivo, indicating that various PI affect distinct metabolic pathways.

PMID- 10958838
TI  - The interrelationship between body topology and body composition varies with age
      among women.
AB  - The purpose of this analysis was to evaluate the relationship between age and the
      size and distribution of the fat and lean tissue compartments in a population
      based sample of women. The study population consisted of the 875 women aged 18-94
      y in the Iowa Bone Health Study who reported never smoking. Fat mass and lean
      mass were measured using dual X-ray absorptiometry. Hip and waist circumference
      and height were measured using standardized protocols. Regression was used to
      model the associations among age, composition and topology measures. When fat
      mass was modeled as a function of hip and waist circumference as well as age,
      age(2) and height, the age x height and age x waist circumference interaction
      terms remained in the fitted model and collectively accounted for 91% of the
      variance. In contrast, the quadratic model of age alone accounted for 8% of the
      observed variance in fat mass. Lean mass was modeled in two segments, with age
      dichotomized at 58 y. Age alone did not predict lean mass in women <58 y but did
      predict lean mass in women >/=58 y, with the modeled relationship including
      interactions with waist circumference and height. These models accounted for 70%
      of observed variance in lean mass. Age is associated with body composition but
      explains <10% of variation. When measures of height and circumferences are
      available, amounts of lean and fat mass are highly predictable. This is
      particularly important for lean mass because no other surrogate measures exist
      for lean mass, whereas there are surrogates for fat mass, including body mass
      index.

PMID- 10958837
TI  - Olive oil phenols inhibit human hepatic microsomal activity.
AB  - We have examined the inhibition of human hepatic microsomal androstenedione 6beta
      hydroxylation and both reductive and oxidative 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) activity by complex phenols found in olive oil.
      Structurally similar compounds were also examined for comparison. Androstenedione
      6beta-hydroxylase activity was inhibited by oleuropein glycoside, hydroxytyrosol
      and gallic acid. Oleuropein glycoside, hydroxytyrosol, gallic acid and
      dihydroxybenzoic acid also inhibited reductive 17beta-HSD activity. Oxidative
      17beta-HSD activity was not inhibited by any of the compounds tested; however
      gallic acid stimulated activity by approximately 30%. Androstenedione 6beta
      hydroxylase activity showed atypical kinetics. For oleuropein glycoside,
      hydroxytyrosol and gallic acid the apparent K(i) values were determined to be 80,
      77 and 70 micromol/L, respectively. Analysis of structural features of inhibitory
      compounds established that a 3,4-dihydroxyphenyl ethanol structure was required
      for inhibition of androstenedione 6beta-hydroxylase for this group of compounds.

PMID- 10958839
TI  - Iron status and stores decline with age in Lewis rats.
AB  - In the context of a larger study examining the interaction of vitamin A (VA)
      status and age on immune function, we examined age-related changes in hematologic
      and iron status variables in male Lewis rats. Animals were fed a nutritionally
      adequate purified diet containing either 0.35 (marginal), 4.0 (control) or 50
      (supplemented) mg retinol equivalents (as retinyl palmitate) per kg of diet from
      the time of weaning until killing at 8-10 (middle-aged) or 20-22 (old) mo of age.
      Neither VA nor VA and age interaction effects were significant for most iron
      variables examined. After controlling for body weight, old rats had significantly
      lower hemoglobin, hematocrit and plasma iron than middle-aged rats. This decrease
      in hematologic and transport iron variables was not accompanied by a shift of
      iron into other storage compartments. Old rats also had significantly lower total
      iron content and iron concentration in liver, spleen and bone marrow. Hemosiderin
      iron in marrow smears correlated significantly (r = 0.43-0.76, P: < 0.05) with
      chemical estimates of iron in storage, transport and functional pools. Old rats
      also tended to have less stained iron in femur marrow smears. Thus, body iron in
      functional, transport and storage compartments, namely the liver, spleen and bone
      marrow, were significantly lower in old than in middle-aged rats. Although iron
      stores and status are usually considered to increase with advancing age, our data
      show a consistent pattern of lower hematologic and storage iron variables in old
      than in middle-aged Lewis rats. Future research is indicated to understand the
      biology and functional consequences of the observed age-associated decline in
      body iron.

PMID- 10958840
TI  - Selenium from high selenium broccoli protects rats from colon cancer.
AB  - Colon cancer is the third most common newly diagnosed cancer in the United States
      and the third most common cause of cancer-related deaths. Previous
      supplementation studies have demonstrated the efficacy of selenium (Se) for
      prevention of colon cancer in humans. The metabolism of Se depends on its
      chemical form, and studies have shown that the chemical form of Se in broccoli
      does not accumulate in the body as fast as other forms of Se and may be
      especially beneficial for prevention of cancer. In the first experiment of the
      present study, Fisher F-344 rats (n = 45) were allotted randomly to torula yeast
      based diets supplemented with the following: 1) no Se; 2) 0.1 microg Se/g diet as
      selenate; 3) 1.0 microg Se/g diet as selenate; 4) 0.1 microg Se/g diet as
      selenized broccoli (Se concentration of approximately 500 microg/g); or 5) 1.0
      microg Se/g diet as selenized broccoli. In Experiment 2, rats (n = 80) were
      allotted randomly to the same basal diet supplemented with the following: 1) no
      added Se; 2) 2.0 microg Se/g diet as selenite; 3) 2. 0 microg Se/g diet as
      selenite + low Se broccoli; and 4) 2.0 microg Se/g diet as selenized broccoli.
      Rats were fed the diets for 2 wk and injected with a chemical carcinogen (3,2
      dimethyl 4-amino biphenyl or dimethyl-hydrazine in Experiment 1 or dimethyl
      hydrazine in Experiment 2; 2 rats/treatment were used as vehicle controls).
      Supranutritional amounts of Se supplied as high Se broccoli significantly
      decreased (P: < 0.05) the incidence of aberrant crypts (AC) and aberrant crypt
      foci (ACF; preneoplastic lesions indicative of colon cancer) compared with other
      dietary treatments. Diets were controlled for the presence or absence of broccoli
      and for the total amount of Se. The reduction in AC and ACF was a function of Se
      in high Se broccoli and not a result of broccoli alone or Se alone. Adequate
      dietary Se supplied as high Se broccoli did not accumulate in tissues or increase
      glutathione peroxidase activity as well as other forms and amounts of Se. Thus,
      Se from high Se broccoli may be metabolized in a manner that diverts much of the
      Se into a pool that provides protection against colon cancer.

PMID- 10958841
TI  - Comments on the review by Nguyen et al. (1999). "The cholesterol-lowering action
      of plant stanol esters".

PMID- 10958842
TI  - Dietary intake in an older urban population.

PMID- 10958843
TI  - Walnuts lower serum cholesterol in Japanese men and women.

PMID- 10958844
TI  - Microsatellite variability differs between dinucleotide repeat motifs-evidence
      from Drosophila melanogaster.
AB  - Recently, the use of microsatellites as genetic markers has become very popular.
      While their evolutionary dynamics are not yet fully understood, the emerging
      picture is that several factors are influencing microsatellite mutation rates.
      Recent experiments demonstrated a significant effect of repeat motif length on
      microsatellite mutation rates. Here, we studied the influence of the base
      composition of the microsatellite. Forty-two microsatellite loci on the second
      chromosome with the three most abundant dinucleotide repeat motifs (TC/AG, AT/TA,
      GT/CA) were characterized for six different Drosophila melanogaster populations.
      Applying ANOVA to the variance in repeat number, we found a significant influence
      of repeat motif on microsatellite variability. Calculating relative mutation
      rates, GT/CA appears to have the highest mutation rate, and AT/TA appears to have
      the lowest. Similar differences in mutation rates were obtained by an alternative
      method which estimates microsatellite mutation rates from their genomic length
      distribution.

PMID- 10958845
TI  - Evolutionary diversification of multigene families: allelic selection of toxins
      in predatory cone snails.
AB  - In order to investigate the evolution of conotoxin multigene families among two
      closely related vermivorous CONUS: species, we sequenced 104 four-loop conotoxin
      mRNAs from two individuals of CONUS: ebraeus and compared these with sequences
      already obtained from CONUS: abbreviatus. In contrast to the diversity of
      conotoxin sequences obtained from C. abbreviatus, only two common sequence
      variants were recovered from C. ebraeus. Segregation patterns of the variants in
      these two individuals and restriction digests of four-loop conotoxin
      amplification products from nine additional individuals suggest that the common
      variants are alleles from a single locus. These two putative alleles differ at
      nine positions that occur nonrandomly in the toxin-coding region of the
      sequences. Moreover, all substitutions are at nonsynonymous sites and are
      responsible for seven amino acid differences among the predicted amino acid
      sequences of the alleles. These results imply that conotoxin diversity is driven
      by strong diversifying selection and some form of frequency-dependent or
      overdominant selection at conotoxin loci, and they suggest that diverse conotoxin
      multigene families can originate from duplications at polymorphic loci.
      Furthermore, none of the sequences recovered from C. ebraeus appeared to be
      orthologs of loci from C. abbreviatus, and attempts to amplify orthologous
      sequences with locus-specific primers were unsuccessful among these species.
      These patterns suggest that venoms of closely related CONUS: species may differ
      due to the differential expression of conotoxin loci.

PMID- 10958846
TI  - The origin of the Jingwei gene and the complex modular structure of its parental
      gene, yellow emperor, in Drosophila melanogaster.
AB  - Jingwei (jgw) is the first gene found to be of sufficiently recent origin in
      Drosophila to offer insights into the origin of a gene. While its chimerical gene
      structure was partially resolved as including a retrosequence of alcohol
      dehydrogenase (ADH:), the structure of its non-ADH: parental gene, the donor of
      the N-terminal domain of jgw, is unclear. We characterized this non-ADH: parental
      locus, yellow emperor (ymp), by cloning it, mapping it onto the polytene
      chromosomes, sequencing the entire locus, and examining its expression patterns
      in Drosophila melanogaster. We show that ymp is located in the 96-E region; the N
      terminal domain of ymp has donated the non-ADH: portion of jgw via a duplication.
      The similar 5' portions of the gene and its regulatory sequences give rise to
      similar testis-specific expression patterns in ymp and jgw in Drosophila
      teissieri. Furthermore, between-species comparison of ymp revealed purifying
      selection in the protein sequence, suggesting a functional constraint in ymp.
      While the structure of ymp provides clear information for the molecular origin of
      the new gene jgw, it unexpectedly casts a new light on the concept of genes. We
      found, for the first time, that the single locus of the ymp gene encompasses
      three major molecular mechanisms determining structure of eukaryotic genes: (1)
      the 5' exons of ymp are involved in an exon-shuffling event that has created the
      portion recruited by jgw; (2) using alternative cleavage sites and alternative
      splicing sites, the 3' exon groups of ymp produce two proteins with nonhomologous
      C-terminal domains, both exclusively in the testis; and (3) in the opposite
      strand of the third intron of ymp is an essential gene, musashi (msi), which
      encodes an RNA-binding protein. The composite gene structure of ymp manifests the
      complexity of the gene concept, which should be considered in genomic research,
      e.g., gene finding.

PMID- 10958847
TI  - Chloroplast DNA inversion polymorphism in populations of Abies and Tsuga.
AB  - Polymorphism for a 42-kb chloroplast DNA inversion was detected in five species
      of Abies and two species of Tsuga based on a sample of 1,281 individuals and both
      Southern hybridization and polymerase chain reaction (PCR) analyses. Two
      haplotypes were observed in all populations and species. The 42-kb inversion is
      associated with a short inverted repeat that includes trnS, psaM, and trnG. The
      frequencies of the two haplotypes within species were very similar among the five
      species of Abies This polymorphism has been maintained within populations and
      species in both Abies and Tsuga, probably because the mutation rate of the
      inversion is high. Haplotype frequencies had no geographical tendencies for any
      species except Abies mariesii, in which haplotype frequencies varied clinally,
      possibly as a result of rapid dissemination after the most recent glacial period
      and random genetic drift.

PMID- 10958848
TI  - Molecular and evolutionary analysis of two divergent subfamilies of a novel
      miniature inverted repeat transposable element in the yellow fever mosquito,
      Aedes aegypti.
AB  - A novel family of miniature inverted repeat transposable elements (MITEs) named
      Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the
      characteristics of MITEs, including terminal inverted repeats, no coding
      potential, A+T richness, small size, and the potential to form stable secondary
      structures. Past mobility of PONY: was indicated by the identification of two
      Pony insertions which resulted in the duplication of the TA dinucleotide targets.
      Two highly divergent subfamilies, A and B, were identified in A. aegypti based on
      sequence comparison and phylogenetic analysis of 38 elements. These subfamilies
      showed less than 62% sequence similarity. However, within each subfamily, most
      elements were highly conserved, and multiple subgroups could be identified,
      indicating recent amplifications from different source genes. Different scenarios
      are presented to explain the evolutionary history of these subfamilies. Both
      subfamilies share conserved terminal inverted repeats similar to those of the Tc2
      DNA transposons in Caenorhabditis elegans, indicating that Pony may have been
      borrowing the transposition machinery from a Tc2-like transposon in mosquitoes.
      In addition to the terminal inverted repeats, full-length and partial subterminal
      repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the
      conservation between the two subfamilies, indicating that they may be important
      structural and/or functional components of the Pony elements. In contrast to
      known autonomous DNA transposons, both subfamilies of PONY: are highly reiterated
      in the A. aegypti genome (8,400 and 9, 900 copies, respectively). Together, they
      constitute approximately 1. 1% of the entire genome. Pony elements were
      frequently found near other transposable elements or in the noncoding regions of
      genes. The relative abundance of MITEs varies in eukaryotic genomes, which may
      have in part contributed to the different organizations of the genomes and
      reflect different types of interactions between the hosts and these widespread
      transposable elements.

PMID- 10958849
TI  - Rapid and parallel chromosomal number reductions in muntjac deer inferred from
      mitochondrial DNA phylogeny.
AB  - Muntjac deer (Muntiacinae, Cervidae) are of great interest in evolutionary
      studies because of their dramatic chromosome variations and recent discoveries of
      several new species. In this paper, we analyze the evolution of karyotypes of
      muntjac deer in the context of a phylogeny which is based on 1,844-bp
      mitochondrial DNA sequences of seven generally recognized species in the muntjac
      subfamily. The phylogenetic results support the hypothesis that karyotypic
      evolution in muntjac deer has proceeded via reduction in diploid number. However,
      the reduction in number is not always linear, i.e., not strictly following the
      order: 46-->14/13-->8/9-->6/7. For example, Muntiacus muntjak (2n = 6/7) shares a
      common ancestor with Muntiacus feae (2n = 13/14), which indicates that its
      karyotype was derived in parallel with M. feae's from an ancestral karyotype of
      2n >/= 13/14. The newly discovered giant muntjac (Muntiacus vuquangensis) may
      represent another parallel reduction lineage from the ancestral 2n = 46
      karyotype. Our phylogenetic results indicate that the giant muntjac is relatively
      closer to Muntiacus reevesi than to other muntjacs and may be placed in the genus
      Muntiacus Analyses of sequence divergence reveal that the rate of change in
      chromosome number in muntjac deer is one of the fastest in vertebrates. Within
      the muntjac subfamily, the fastest evolutionary rate is found in the Fea's
      lineage, in which two species with different karyotypes diverged in around 0.5
      Myr.

PMID- 10958850
TI  - The complete mitochondrial genome of Tupaia belangeri and the phylogenetic
      affiliation of scandentia to other eutherian orders.
AB  - The complete mitochondrial genome of Tupaia belangeri, a representative of the
      eutherian order Scandentia, was determined and compared with full-length
      mitochondrial sequences of other eutherian orders described to date. The complete
      mitochondrial genome is 16, 754 nt in length, with no obvious deviation from the
      general organization of the mammalian mitochondrial genome. Thus, features such
      as start codon usage, incomplete stop codons, and overlapping coding regions, as
      well as the presence of tandem repeats in the control region, are within the
      range of mammalian mitochondrial (mt) DNA variation. To address the question of a
      possible close phylogenetic relationship between primates and Tupaia, the
      evolutionary affinities among primates, Tupaia and bats as representatives of the
      Archonta superorder, ferungulates, guinea pigs, armadillos, rats, mice, and
      hedgehogs were examined on the basis of the complete mitochondrial DNA sequences.
      The opossum sequence was used as an outgroup. The trees, estimated from 12
      concatenated genes encoded on the mitochondrial H-strand, add further molecular
      evidence against an Archonta monophyly. With the new data described in this
      paper, most of both the mitochondrial and the nuclear data point away from
      Scandentia as the closest extant relatives to primates. Instead, the complete
      mitochondrial data support a clustering of Scandentia with Lagomorpha connecting
      to the branch leading to ferungulates. This closer phylogenetic relationship of
      Tupaia to rabbits than to primates first received support from several analyses
      of nuclear and partial mitochondrial DNA data sets. Given that short sequences
      are of limited use in determining deep mammalian relationships, the partial
      mitochondrial data available to date support this hypothesis only tentatively.
      Our complete mitochondrial genome data therefore add considerably more evidence
      in support of this hypothesis.

PMID- 10958851
TI  - Duplication, dicistronic transcription, and subsequent evolution of the Alcohol
      dehydrogenase and Alcohol dehydrogenase-related genes in Drosophila.
AB  - It has recently been discovered that the Alcohol dehydrogenase and Alcohol
      dehydrogenase-related genes of Drosophila melanogaster and closely related
      species constitute a single transcription unit and that the Alcohol dehydrogenase
      related gene is exclusively expressed from a dicistronic mRNA. Here, we show that
      in Drosophila lebanonensis, subgenus Scaptodrosophila, Adhr: is also transcribed
      as a dicistronic transcript with Adh Using degenerate primers designed on the
      sequence of the known Adhr proteins, we have been able to amplify and sequence a
      partial sequence of Adhr: in species representative of the whole subgenus
      Drosophila. This has allowed the study of the organization and expression of
      Adhr: in Drosophila buzzatii. We find that in D. buzzatii Adhr is transcribed as
      a monocistronic transcript. Adh and Adhr are believed to originate by
      duplication, and our data suggest that the cotranscription of these two genes was
      the primitive state, and that their independent transcription in the subgenus
      Drosophila is derived. We can rationalize the D. buzzatii condition as being
      correlated with the two genes evolving independent transcriptional control.
      However, why these two genes with clear divergence in the functions of their
      proteins should remain cotranscribed in groups as divergent as the subgenus
      Sophophora and the subgenus Scaptodrosophila remains a mystery.

PMID- 10958852
TI  - Actin gene family evolution and the phylogeny of coleoid cephalopods (Mollusca:
      Cephalopoda).
AB  - Phylogenetic analysis conducted on a 784-bp fragment of 82 actin gene sequences
      of 44 coleoid cephalopod taxa, along with results obtained from genomic Southern
      blot analysis, confirmed the presence of at least three distinct actin loci in
      coleoids. Actin isoforms were characteri zed through phylogenetic analysis of
      representative cephalopod sequences from each of the three isoforms, along with
      translated actin cDNA sequences from a diverse array of metazoan taxa downloaded
      from GenBank. One of the three isoforms found in cephalopods was closely related
      to actin sequences expressed in the muscular tissues of other molluscs. A second
      isoform was most similar to cytoplasmic-specific actin amino acid sequences. The
      muscle type actins of molluscs were found to be distinct from those of
      arthropods, suggesting at least two independent derivations of muscle actins in
      the protostome lineage, although statistical support for this conclusion was
      lacking. Parsimony and maximum-likelihood analyses of two of the isoforms from
      which >30 orthologous coleoid sequences had been obtained (one of the cytoplasmic
      actins and the muscle actin) supported the monophyly of several higher-level
      coleoid taxa. These included the superorders Octopodiformes and Decapodiformes,
      the order Octopoda, the octopod suborder Incirrata, and the teuthoid suborder
      Myopsida. The monophyly of several taxonomic groups within the Decapodiformes was
      not supported, including the orders Teuthoidea and Sepioidea and the teuthoid
      suborder Oegopsida. Parametric bootstrap analysis conducted on the simulated
      cytoplasmic actin data set provided statistical support to reject the monophyly
      of the Sepioidea. Although parametric bootstrap analysis of the muscle actin
      isoform did not reject sepioid monophyly at the 5% level, the results (rejection
      at P: = 0.068) were certainly suggestive of sepioid nonmonophyly.

PMID- 10958853
TI  - Cytosine deamination plays a primary role in the evolution of mammalian
      isochores.
AB  - DNA melting is rate-limiting for cytosine deamination, from which we infer that
      the rate of cytosine deamination should decline twofold for each 10% increase in
      GC content. Analysis of human DNA sequence data confirms that this is the case
      for 5-methylcytosine. Several lines of evidence further confirm that it is also
      the case for unmethylated cytosine and that cytosine deamination causes the
      majority of all C-->T and G-->A transitions in mammals. Thus, cytosine
      deamination and DNA base composition each affect the other, forming a positive
      feedback loop that facilitates divergent genetic drift to high or low GC content.
      Because a 10 degrees C increase in temperature in vitro increases the rate of
      cytosine deamination 5. 7-fold, cytosine deamination must be highly dependent on
      body temperature, which is consistent with the dramatic differences between the
      isochores of warm-blooded versus cold-blooded vertebrates. Because this process
      involves both DNA melting and positive feedback, it would be expected to spread
      progressively (in evolutionary time) down the length of the chromosome, which is
      consistent with the large size of isochores in modern mammals.

PMID- 10958854
TI  - A 39-kb sequence around a blackbird Mhc class II gene: ghost of selection past
      and songbird genome architecture.
AB  - To gain an understanding of the evolution and genomic context of avian major
      histocompatibility complex (Mhc) genes, we sequenced a 38.8-kb Mhc-bearing cosmid
      insert from a red-winged blackbird (Agelaius phoeniceus). The DNA sequence, the
      longest yet retrieved from a bird other than a chicken, provides a detailed view
      of the process of gene duplication, divergence, and degeneration ("birth and
      death") in the avian Mhc, as well as a glimpse into major noncoding features of a
      songbird genome. The peptide-binding region (PBR) of the single Mhc class II B
      gene in this region, Agph-DAB2, is almost devoid of polymorphism, and a still
      segregating single-base-pair deletion and other features suggest that it is
      nonfunctional. Agph-DAB2 is estimated to have diverged about 40 MYA from a
      previously characterized and highly polymorphic blackbird Mhc gene, Aph-DAB1, and
      is therefore younger than most mammalian Mhc paralogs and arose relatively late
      in avian evolution. Despite its nonfunctionality, Agph-DAB2 shows very high
      levels of nonsynonymous divergence from Agph-DAB1 and from reconstructed
      ancestral sequences in antigen-binding PBR codons-a strong indication of a period
      of adaptive divergence preceding loss of function. We also found that the region
      sequenced contains very few other unambiguous genes, a partial Mhc- class II gene
      fragment, and a paucity of simple-sequence and other repeats. Thus, this sequence
      exhibits some of the genomic streamlining expected for avian as compared with
      mammalian genomes, but is not as densely packed with functional genes as is the
      chicken Mhc.

PMID- 10958855
TI  - Genetic structure of a 2,500-year-old human population in China and its
      spatiotemporal changes.
AB  - To examine temporal changes in population genetic structure, we compared the
      mitochondrial DNA (mtDNA) sequences of three populations that lived in the same
      location, Linzi, China, in different periods: 2,500 years ago (the Spring-Autumn
      era), 2,000 years ago (the Han era), and the present day. Two indices were used
      to compare the genetic differences: the frequency distributions of the radiating
      haplotype groups and the genetic distances among the populations. The results
      indicate that the genetic backgrounds of the three populations are distinct from
      each other. Inconsistent with the geographical distribution, the 2,500-year-old
      Linzi population showed greater genetic similarity to present-day European
      populations than to present-day east Asian populations. The 2, 000-year-old Linzi
      population had features that were intermediate between the present-day
      European/2,500-year-old Linzi populations and the present-day east Asian
      populations. These relationships suggest the occurrence of drastic spatiotemporal
      changes in the genetic structure of Chinese people during the past 2,500 years.

PMID- 10958856
TI  - NJML: a hybrid algorithm for the neighbor-joining and maximum-likelihood methods.
AB  - In the reconstruction of a large phylogenetic tree, the most difficult part is
      usually the problem of how to explore the topology space to find the optimal
      topology. We have developed a "divide-and-conquer" heuristic algorithm in which
      an initial neighbor-joining (NJ) tree is divided into subtrees at internal
      branches having bootstrap values higher than a threshold. The topology search is
      then conducted by using the maximum-likelihood method to reevaluate all branches
      with a bootstrap value lower than the threshold while keeping the other branches
      intact. Extensive simulation showed that our simple method, the neighbor-joining
      maximum-likelihood (NJML) method, is highly efficient in improving NJ trees.
      Furthermore, the performance of the NJML method is nearly equal to or better than
      existing time-consuming heuristic maximum-likelihood methods. Our method is
      suitable for reconstructing relatively large molecular phylogenetic trees (number
      of taxa >/= 16).

PMID- 10958857
TI  - Positive selection in the evolution of mammalian interleukin-2 genes.

PMID- 10958859
TI  - Stability of prothrombin time and activated partial thromboplastin time tests
      under different storage conditions.
AB  - Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are common
      laboratory tests that are useful in the diagnosis of coagulation disorders and
      monitoring anticoagulant therapy. Recent expansions in the outreach laboratory
      services at our institution prompted us to investigate the shipping limitations
      for some tests, including PT and aPTT. Although we followed NCCLS guidelines for
      the collection of blood specimens, we observed falsely elevated PT and aPTT
      values due to the different storage conditions. The objective of this study is to
      determine the effect of conditions and duration of storage on PT and aPTT tests
      using plasma and whole blood samples, respectively. For this study, 36 plasma
      samples with normal and prolonged PT and aPTT were exposed to different storage
      conditions. Blood was centrifuged immediately and plasma was stored at room
      temperature (RT), refrigerated at 4 degrees C, or frozen at -20 degrees C. The
      samples were analyzed at 0 h and repeated at 6, 12 and 24 h under various
      conditions. Although statistically significant differences were observed for
      plasma samples for normal PT tests after 12 h at refrigerated and frozen storage
      conditions, the differences would not change the clinical interpretation of the
      results. On the other hand, samples stored refrigerated or at RT showed
      significant differences for aPTT at 24 h. These differences would change clinical
      interpretation, especially for samples with normal or near normal aPTT times.
      Interestingly, aPTT was significantly higher for samples stored frozen when
      compared to refrigerated and RT conditions at 6 h. Similar patterns were also
      observed on ten whole blood samples with normal PT and aPTT values. In
      conclusion, either plasma or whole blood samples can be accepted for PT testing
      up to 24 h and for aPTT testing up to 12 h only, when transported either at RT or
      at 4 degrees C.

PMID- 10958858
TI  - Inability of propranolol to prevent alcohol-induced reductions in cardiac protein
      synthesis in vivo.
AB  - Rats were acutely injected with alcohol (75 mmol/kg body weight) and at the end
      of 2.5 h changes in cardiac synthesis rates were assessed with a 'flooding dose'
      of L-[4-(3)H]phenylalanine. The results showed that acute alcohol dosage reduced
      the fractional rates of cardiac protein synthesis (k(S), %/day). This effect was
      also seen when data were expressed relative to either RNA (i.e. k(RNA), mg
      protein/day/mg RNA) or DNA (i.e. k(DNA), mg protein/day/mg DNA). Both left and
      right ventricles responded similarly to ethanol. However, propranolol pre
      treatment (at doses of 17 and 170 micromol/kg body weight; i.p.) did not prevent
      these effect of ethanol in either the left or right ventricle. Indeed, there was
      evidence that propranolol per se perturbed cardiac protein synthesis in vivo in
      control (i.e. without ethanol) rats particularly in the right ventricle. In
      conclusion, the results suggest that alcohol is cardiotoxic to the myocardium,
      which may cause its effects on protein synthesis independently of beta-receptors
      and/or xanthine oxidase inhibition.

PMID- 10958860
TI  - In vitro effects of mycophenolic acid on cell cycle and activation of human
      lymphocytes.
AB  - The immunosuppressant mycophenolic acid (MPA) selectively inhibits proliferation
      of T- and B-lymphocytes by blocking inosine 5'-monophosphate-dehydrogenase
      (IMPDH), the key enzyme for de-novo-synthesis of guanine nucleotides. In an in
      vitro study the effects of MPA on human peripheral blood lymphocyte activation
      markers and on cell cycle characteristics were investigated. Mononuclear cells
      from healthy volunteers were incubated with phytohaemagglutinin (PHA) and
      increasing doses of MPA. After 72 h incubation an aliquot of the cells was
      stained with propidium iodide and measured by FACS analyses to assess the DNA
      shape. In addition, the expression of the activation markers HLA-DR and CD25 on T
      and B-lymphocytes was determined by flow cytometry analysis.PHA stimulation led
      to a significant increase of the S-phase of cell cycle. PHA stimulation clearly
      increased mean fluorescence intensity (MFI) of HLA-DR expression on B
      lymphocytes. PHA stimulation also elevated the number of CD25 positive B
      lymphocytes. Expression of HLA-DR on T-lymphocytes was not influenced by PHA,
      whereas CD25 expression and MFI significantly increased. All the observed PHA
      induced effects were reduced by co-incubation with increasing doses of MPA. The
      data presented show that in vitro the immunosuppressive effect of MPA can be
      demonstrated using FACS technology on a cellular level. MPA leads to an
      inhibition of cell cycle proliferation in peripheral blood lymphocytes.

PMID- 10958861
TI  - Immunochemical detection of imidazolone in uremia and rheumatoid arthritis.
AB  - The advanced glycation end-product imidazolone is formed by reaction of arginine
      with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction,
      whose formation is non-oxidative. Using an antibody specific to this 3-DG-derived
      AGE, we demonstrated the presence of imidazolone-modified proteins in vivo in the
      urine and dialysate of patients with chronic renal failure, in the synovial fluid
      of patients with rheumatoid arthritis, as well as in vitro in human serum and
      human serum albumin incubated with glucose. Furthermore, we could show that in
      uremic patients the dimeric form of beta(2)-microglobulin is more susceptible to
      imidazolone modification than the monomeric one. Thus, the immunochemical
      detection of imidazolone may be a good marker for 3-DG-derived AGE modification
      in vivo and in vitro permitting a differentiation between the oxidative and the
      non-oxidative pathway of AGE generation.

PMID- 10958862
TI  - Diagnostic usefulness of tumour marker levels in pleural effusions of malignant
      and benign origin.
AB  - Pleural effusion is a common diagnostic problem. The analysis of serum and body
      fluids for tumor markers has been intensively applied to clinical diagnosis. The
      aim of the present study was to determine the usefulness of simultaneous
      quantification of carbohydrate antigen 19.9, carbohydrate antigen 125, neuron
      specific enolase, mucinous-carcinoma-associated antigen, and ferritin in samples
      of pleural fluids in the malign pleural effusion and its differentiation from
      benign effusions. A total of 61 pleural effusions were collected from the
      patients, who were subjected either to simple needle aspiration or to tube
      drainage for the diagnosis of pleural effusion. Tumor markers were determined in
      benign patient groups with nonspecific pleurisy, tuberculous pleurisy, empyema,
      congestive heart failure and in malignancy groups consisting of adenocarcinoma,
      small cell lung carcinoma, mesothelioma, epidermoid lung cancer. The tumor
      markers CA-19.9, CA-125, NSE, and ferritin levels were quantified by the sandwich
      assay using the streptavidin technology of ELISA in an ES-300 Boehringer-Mannheim
      analyser. MCA was measured by employing a two-side solid phase EIA method. MCA
      measurements were done by the Cobas-Core. For all patients, the effusions
      correctly or incorrectly identified by the different procedures as being
      malignant or nonmalignant are defined as true positive, false positive, true
      negative, and false negative, the term 'positive' referring to histologically
      proven malignant pleural effusion while nonmalignant effusions are referred to as
      'negative'. Therefore, sensitivity, specificity, positive predictive value, and
      negative predictive value were defined as diagnostic parameters. The cut-off
      values calculated were 352 U/ml for CA-125, 54 U/ml for CA-19.9, 555 for
      ferritin, 11.1 for MCA and 8.7 for NSE. In our study, the highest sensitivity is
      found to be MCA with 100%; specificity, CA-19.9 with 97%; PPV, CA-19.9 and MCA
      with 95% and NPV, MCA with 100%. Our data imply that the co-measurement of MCA+CA
      19.9+CA-125 levels may further improve their diagnostic value in malignant
      pleural effusion compared with that of each tumour marker alone and may be useful
      in distinguishing malignant from benign pleural effusions.

PMID- 10958863
TI  - CK-MB isoforms for early risk stratification of emergency department patients.
AB  - The potential clinical utility of single sample CK-MB isoforms measurement for
      early risk stratification of Emergency Department (ED) patients with possible
      myocardial ischemia was evaluated among 405 patients presenting to two urban EDs.
      Clinical and serologic data were prospectively collected and the occurrence of
      adverse events (AEs) and myocardial infarction (MI) during the 14-day outcome
      period was recorded and utilized to calculate and compare relative risks (RR) and
      predictive values of isoforms and CK-MB alone. Among the 405 patients, 67 accrued
      105 AEs. Both isoforms and CK-MB alone were predictive of AEs with RR of 3.32
      (2.09, 5.27) and 6.28 (4.64, 8.52), respectively. Isoforms had higher sensitivity
      for AEs compared to CK-MB (65.7% [54.3, 77.0] vs. 14.9% [6.4, 23.5]; p<0. 01) but
      lower specificity (69.2% [64.3, 74.2] vs. 99.7% [99.1,100. 0]; p<0.01). Isoforms'
      superior sensitivity allowed identification of many high risk patients missed by
      CK-MB alone. Further, for the prediction of MI, isoforms had superior diagnostic
      sensitivity and equivalent specificity. This investigation supports the emergency
      department use of early, single sample CK-MB isoform testing.

PMID- 10958864
TI  - Age group-associated variations in the pattern of Hp type distribution in
      Jordanians.
AB  - The relationship between haptoglobin (Hp) type and life expectancy was
      investigated by determining the pattern of Hp type distribution in 790 unrelated
      Jordanians divided into four age groups: A (1-19 years), B (20-39 years), C (40
      59 years) and D (60-85 years). While the frequency of Hp 2-2 gradually decreased
      from 0.576 in A to 0.393 in D, the frequency of Hp 2-1 gradually increased from
      0.348 in A to 0.526 in D. Hp2 allele decreased from 0.750 in A to 0.656 in D
      while that of Hpl allele increased from 0.250 in A to 0.344 in D. Hp type
      distribution in A, B and D age groups was in agreement with the Hardy-Weinberg
      equilibrium (HWE). These findings demonstrate that the pattern of Hp polymorphism
      varies in different age groups, indicating that life expectancy might be Hp
      phenotype-associated. Additionally, the results suggest that Hp 2-2 phenotype
      might be an age-associated risk factor.

PMID- 10958865
TI  - Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in
      asthmatic patients.
AB  - The effect of asthma pathogenesis on serum cystatin C, a potent inhibitor of
      cysteine proteinases and a newly proposed marker of the renal function, has not
      been yet determined. The objectives were to determine the 24-h pattern of
      cystatin C and creatinine concentrations in sera of asthmatic patients in order
      to test whether their concentrations might reflect circadian rhythms, the disease
      severity and the effect of therapy. Serum concentrations of cystatin C and
      creatinine were determined in steroid-independent and steroid-dependent
      asthmatics before and after 1 week of treatment with methylprednisolone and
      cyclosporin A, respectively. Samples were collected every 4 h during a 24-h
      period. Little or no significant effects of time on cystatin C and creatinine
      concentrations over a 24-h period were observed in healthy and asthmatic sera.
      However, significantly higher cystatin C concentrations were found in asthmatic
      patients compared to controls which suggests its role in the pathogenesis of
      asthma. Methylprednisolone increased and cyclosporin A decreased serum cystatin C
      concentrations after 1 week of therapy. Additionally these results support the
      need for the evaluation of cystatin C as a marker of glomerular filtration rate
      determination in asthma.

PMID- 10958866
TI  - Seminal quality correlates with mitochondrial functionality.
AB  - Oligozoospermia is an important manifestation of male subfertility and very
      little attention has been paid to study a possible relationship between the total
      number of ejaculated spermatozoa and mitochondrial functionality. In this work we
      report a direct correlation between spectrophotometrically measured mitochondrial
      enzyme activities (citrate synthase and respiratory complex I, II, I+III, II+III
      and IV) and seminogram parameters (sperm motility, vitality and cell
      concentration). In addition, total ejaculated spermatozoa correlate much better
      with the nuclear-encoded citrate synthase and complex II than with the
      mitochondrial-encoded complex I, III and IV activities. Furthermore, total number
      of spermatozoa has a significant but negative correlation with the ratios of
      complex I, complex III and complex IV to complex II (and citrate synthase). These
      ratios are significantly higher in aged subjects emphasizing the physiological
      relevance of this observation. These results suggest that the simultaneous
      increase of the number of ejaculated spermatozoa and the mitochondrial enrichment
      of citrate synthase and complex II are both parallel responses to the same
      regulatory events.

PMID- 10958867
TI  - Free radical activity and antioxidant defense mechanisms in patients with
      hyperthyroidism due to Graves' disease during therapy.
AB  - Free radical-mediated oxidative stress has been implicated in the
      etiopathogenesis of several autoimmune disorders. We investigated the prooxidant
      antioxidant status in order to evaluate the possible deleterious role of
      oxidative phenomena in patients with Graves' disease. Thirty patients with
      hyperthyroidism due to Graves' disease were investigated. Thirty age-matched
      healthy subjects were studied as a control group. Free radical activity indices,
      antioxidant defense systems, and thyroid and pituitary hormone levels were
      measured in fasting blood samples. Blood samples were taken before initiation of
      therapy and after attainment of euthyroid state. A significant increase in lipid
      peroxidation activity indices, i.e., conjugated dienes and thiobarbituric acid
      reacting substances, was found in blood serum of the patients with untreated
      Graves' disease. These changes were accompanied by a decrease in plasma thiol and
      erythrocyte lysate thiol groups concentrations. Hyperthyroidism resulted in a
      marked increase in intracellular antioxidant enzymes, i.e., superoxide dismutase,
      catalase and glutathione peroxidase activities as compared to the controls.
      Extracellular anti-free radical scavenging systems potential, measured by
      glutathione reductase activity and total antioxidant status level, was found to
      be significantly decreased in untreated Graves' patients. Treatment with
      thiamazole resulted in normalization of the free radical and antioxidant activity
      indices. The obtained results indicate an enhanced generation of reactive oxygen
      species and impairment of cellular and extracellular antioxidant systems
      potential in patients with Graves' disease. The attainment of euthyroid state led
      to an improvement in oxidative stress indices and antioxidant potential
      parameters.

PMID- 10958868
TI  - Evidences that zidovudine (AZT) could not be directly responsible for iron
      overload in AZT-treated patients: an in vitro study.
AB  - Zidovudine (3'-azido-3'-deoxythymidine or azidothymidine, AZT) has been the first
      antiretroviral agent approved for clinical use, and it is still currently used in
      combination therapy of human immunodeficency virus (HIV) infection. On the basis
      of increasing clinical reports and in vitro studies, a strict correlation between
      AZT treatment of HIV positive patients and both the development of anemia and
      iron overload have been in evidence over the last few years. In this report, we
      have examined some features of zidovudine to better assess a likely implication
      of this drug in iron overload. For this purpose, we first determinated the iron
      chelating ability of both AZT and some of its phosphorylated derivatives in
      solution. The iron chelating ability of AZT toward the intracellular 'chelatable'
      iron pool was also evaluated. Finally, we investigated the effect of AZT on both
      iron and transferrin uptake. Our findings indicate that AZT per se cannot be
      directly responsible for the development of the iron overload found in human or
      animal models, for which other possible mechanisms are claimed to be involved.

PMID- 10958869
TI  - Enzymatic dopamine peroxidation in substantia nigra of human brain.
AB  - The main metabolic pathway affected in Parkinson's disease is that of dopamine
      oxidation and melanin formation in substantia nigra which involves both oxidative
      and reductive enzymes. The cyclic nature of the biosynthetic pathway from
      dopamine to melanin implies that a derangement at any of the steps may result in
      the disappearance of melanin. Possible pathogenetic events such as oxidative
      stress have therefore no clearcut interpretation since they may be both cause or
      consequence of the disease. This paper documents the existence of a peroxidase
      converting dopamine to dopaminochrome in the presence of hydrogen peroxide in the
      substantia nigra of autopsied human brain. The activatory effect of
      dopaminochrome on a purified peroxidase is shown, together with the inhibitory
      effect of dopaminochrome-derived melanin and the activatory effect of melanin/Fe.
      The toxic effect of dopaminochrome on murine neuroblastoma cells cultured in
      vitro is demonstrated together with the inhibition of dopaminochrome melanization
      induced by acetylcholine in vitro.

PMID- 10958870
TI  - Seven DNA polymorphisms at the candidate genes of atherosclerosis in Brazilian
      women with angiographically documented coronary artery disease.
AB  - The possible association of genetic markers at the apolipoprotein E (HhaI
      polymorphism), apolipoprotein B (XbaI, EcoRI and Ins/Del polymorphisms), and low
      density lipoprotein receptor (LDLR) (AvaII, HincII and PvuII polymorphisms) with
      coronary artery disease (CAD) was evaluated in 50 Brazilian women with CAD
      diagnosed by angiography and in 100 healthy women (controls). The frequency of
      E3/E4 genotype for HhaI polymorphism at the Apo E gene was significantly higher
      in CAD patients than in controls (40% vs. 14%, respectively, P<0.001). Similarly,
      the X-X- genotype for XbaI polymorphism was more frequent in CAD individuals than
      controls (42% vs. 12%, P<0.0001). The A+A+ and P1P1 genotypes for AvaII and PvuII
      polymorphisms at the LDLR locus were also higher in CAD subjects than controls
      (44% vs. 16%, P<0.001 and 64% vs. 39%, P<0.05, respectively). The estimated
      relative risks for CAD in women carrying the E3/E4, X-X-, A+A+ and P1P1 genotypes
      were 4.1 [95% confidence interval (CI), 3.0-5.6], 5.3 (95% CI, 3.8-7.5), 4.1 (95%
      CI, 3.0-5.5), and 2.8 (95% CI, 2.2-3.6), respectively. This study demonstrates
      that Apo E, Apo B and LDLR gene polymorphisms are associated with CAD in
      Brazilian Caucasian women.

PMID- 10958871
TI  - Falsely elevated serum digitoxin concentrations due to cross-reactivity of water
      extractable digitoxin-like immunoreactivity of Chinese medicine Chan SU:
      elimination of interference by use of a chemiluminescent assay.
AB  - Chinese medicines are available without prescription in health food stores. One
      such Chinese preparation, Chan SU, is used as a cardiotonic agent. Digoxin-like
      immunoreactivity of Chan SU has been reported in the past. In this report we
      demonstrated significant digitoxin-like immunoreactivity of Chan SU. For example,
      when a 20-microl aliquot of an aqueous extract of Chan SU (2 mg/ml) was added to
      drug-free serum, the observed digitoxin-like immunoreactivity was 51.40 ng/ml by
      the fluorescence polarization assay. In contrast, a new chemiluminescent assay
      for digitoxin did not show any immunoreactivity. When very small amount of
      aqueous extract of Chan SU was added into serum containing digitoxin, the
      observed digitoxin concentrations were falsely elevated when measured by the
      fluorescence polarization immunoassay (FPIA), but did not change significantly
      when measured by the chemiluminescent immunoassay (CLIA). Significant digitoxin
      like immunoreactivity was also observed (FPIA) in mice after feeding with Chan
      SU. Because bufalin, cinobufotalin and cinobufagin are major components of Chan
      SU, digitoxin-like immunoreactivity of these purified compounds was also studied.
      Bufalin was identified as the major digitoxin-like immunoreactive compound
      responsible for most of the interference in serum digitoxin measurement using the
      FPIA.

PMID- 10958872
TI  - Deletion of p16 and p15 genes In schistosomiasis-associated bladder cancer
      (SABC).
AB  - Alterations of p16 and p15 genes have been reported in cancer cell lines and in
      certain malignant neoplasm. These genes are designated as candidate tumor
      suppressor genes because they encode proteins that function as negative cell
      cycle regulators at G(1)-S checkpoint. One hundred and sixty eight tumor tissue,
      20 schistosomal tissue, and 50 normal tissue samples were examined. The status of
      p16 and p15 genes in these tissues was determined by the polymerase chain
      reaction and by sequencing the DNA fragments produced during PCR. In addition,
      the expression of p16 and p15 proteins was examined by Western blot analysis. p16
      and p15 genes were detected in all normal and schistosomal tissues. Deletion of
      both p16 and p15 genes was observed in 72 and 36 bladder tumors, respectively.
      Twenty eight of the 72 cases that exhibited p16 deletions also displayed
      deletions of p15. Only eight cases showed loss of the p15 gene while retaining
      p16 gene, and p16 deletion with apparently intact p15 gene was identified in 44
      cases. The present analysis also reveals that deletion in the two genes are
      associated with low-stage, low grade bladder cancer, schistosomiasis-associated
      bladder cancer (SABC) and squamous cell carcinoma type (SCC). No point mutations
      were identified in either gene. The expression of p16 and p15 proteins was
      undetectable in 75 and 38 bladder tumors, respectively, by Western blot analysis.
      Alteration of the p16 and p15 genes appears to be an early event in bladder
      cancer which occurs more frequently in SABC and SCC, and may play an important
      role in the development of schistosomal bladder cancer.

PMID- 10958873
TI  - Expression of prostate-specific antigen and human glandular kallikrein 2 in the
      thyroid gland.
AB  - Prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) are two
      closely related kallikreins, primarily produced by the prostate. These serine
      proteases are now used as biomarkers for the diagnosis and management of prostate
      cancer. Until recently, PSA and hK2 were thought to be strictly expressed in the
      prostate; however, numerous studies confirmed their presence in various
      biological fluids as well as in many normal and malignant tissues. Using reverse
      transcription-polymerase chain reaction (RT-PCR), we screened RNA extracted from
      26 different normal tissues and found that both genes are expressed in the
      thyroid. Subsequently, we analyzed 15 RNAs extracted from thyroid tissues (10
      benign and 5 malignant lesions) and found that both kallikreins were expressed in
      five specimens (four benign lesions and one malignant). Sequencing of the PCR
      products confirmed the specificity of our experiments. Immunohistochemistry
      localized PSA in oxyphilic cells of thyroid tissue. These data confirm expression
      of both PSA and hK2 in thyroid tissue and suggest that oxyphils are the source of
      their production. The function of these two proteases in thyroid tissue is
      unknown.

PMID- 10958874
TI  - Comparison of urinary markers for bone resorption in multiple myeloma.
AB  - Multiple myeloma causes extensive bone remodeling. Classical biochemical markers
      such as urinary calcium have poor sensitivity for detecting multiple myeloma bone
      remodeling. New biochemicals have been developed including a carboxyterminal
      telopeptide of collagen I (CTX). We used an immunoenzymatic assay to determine
      urinary CTX in 60 patients with multiple myeloma. This marker was evaluated with
      regard to total pyridinolines, urinary calcium, radiological features, pain and
      response to treatment with bisphosphonates. In patients with bone involvement,
      CTX concentrations were significantly higher (+230%) than those of
      deoxypyridinoline (DPD) (+175%) and pyridinolines (PYD) (+130%). In all patients
      we have found a close correlation between CTX and DPD but not between CTX and
      PYD. Compared to radiological features, CTX was more sensitive (97%) and specific
      (96%) than DPD. After treatment by bisphosphonates, the fall in CTX
      concentrations was paralleled to urinary calcium and more marked than
      pyridinolines. Although our results need to be confirmed, CTX appears to be a
      potential marker to explore bone involvement in multiple myeloma.

PMID- 10958875
TI  - Cystatin C, an early indicator for incipient renal disease in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic
      therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying
      antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal
      status of patients suffering from prolonged RA by means of plasma cystatin C, a
      new parameter of renal function. Fifty-six patients affected with RA for more
      than 5 years, and treated with NSAIDs for more than 50 months, were included in
      the study. Besides conventional markers of renal function (i.e. plasma
      creatinine, estimated glomerular filtration rate, creatinine clearance), we
      analysed plasma cystatin C by an automated, nephelometric immunoassay on a
      Behring nephelometer. Sixty percent of the RA patients exhibited elevated levels
      of plasma cystatin C, whereas only three out of 56 patients showed an elevated
      plasma creatinine, even though the creatinine clearance was decreased in 57% of
      these patients. Cystatin C exhibited a by far better correlation with creatinine
      clearance than plasma creatinine. In conclusion, patients with prolonged RA for
      more than 50 months, show a disturbed renal function despite normal plasma
      creatinine. Elevated cystatin C indicates such incipient renal disease, and is,
      not least because of a simple, well reproducible technique, more recommendable
      for screening purposes than tedious clearance determinations.

PMID- 10958876
TI  - Artefacts in organic acid analysis: occurrence and origin of partially
      trimethylsilylated 3-hydroxy-3-methyl carboxylic acids.
AB  - Previous reports of patients with 3-hydroxy-3-methylglutaric aciduria have
      described the occurrence of di-trimethylsilyl (TMS) and tri-TMS derivatives of 3
      hydroxy-3-methylglutaric acid on analysis using gas chromatography and mass
      spectrometry, leading to difficulty in quantification and ambiguity in diagnosis.
      We have extracted organic acids from the urine of patients with 3-hydroxy-3
      methylglutaric aciduria using a variety of procedures. Solvent extraction
      combined with hydrochloric acid/sodium chloride resulted in production of both di
      TMS and tri-TMS derivatives of 3-hydroxy-3-methylglutaric acid and also mono-TMS
      and di-TMS derivatives of 3-hydroxyisovaleric acid. The effects were not
      abolished by heating. Use of sulphate-based reagents minimised artefact formation
      and use of DEAE-Sephadex anion exchange extraction resulted in single fully
      trimethylsilylated derivatives. Artefact formation during use of chloride-based
      reagents was abolished by pyridine added prior to trimethylsilylation. Chloride
      ions form adducts with hydroxyl groups in these 3-hydroxy-3-methyl carboxylic
      acids that prevent complete trimethylsilylation. Chloride-based reagents should
      be avoided in the solvent extraction of organic acids from physiological fluids
      or, if used, pre-treatment of the dried extract with pyridine is essential to
      avoid partial trimethylsilylation of 3-hydroxy-3-methyl carboxylic acids.

PMID- 10958877
TI  - Knowledge and willingness to use emergency contraception among low-income post
      partum women.
AB  - We performed a multivariate analysis to determine factors associated with
      knowledge and willingness to use emergency contraception in a consecutive sample
      of 371 post-partum women from an inner-city public hospital. Women were queried
      about previous contraceptive use, pregnancy history including abortions and
      unplanned pregnancies, and demographic characteristics. Outcomes included
      knowledge of emergency contraception and willingness to use it. Questionnaires
      were conducted in person, in English or Spanish.Of 371 women, 3% had used
      emergency contraception, 36% had heard of it, and 7% knew the correct timing for
      use. Two-thirds of the population indicated a willingness to use emergency
      contraception in the future. Factors positively associated with knowledge
      included being a teenager or more than 30 years old, prior use of condoms, and
      history of an elective abortion. Being multiparous, monolingual Spanish-speaking,
      or Asian were negatively associated with knowledge. Willingness to use emergency
      contraception was positively associated with being multiparous and negatively
      associated with a higher income, moral or religious objections to the use of
      emergency contraception, a belief that it is unsafe or a perception that it is an
      abortificient. Knowledge about emergency contraception, especially correct
      timing, remains low. Multiparous women should receive increased education given
      their lack of knowledge but willingness to use emergency contraception. In order
      to increase the acceptability of emergency contraception, educational efforts
      must include accurate information about its mechanism of use and safety.

PMID- 10958878
TI  - Intrauterine device use and some issues related to sexually transmitted disease
      screening and occurrence.
AB  - The objective of this study was to compare sexually transmitted disease (STD)
      occurrence and STD complaints in women using intrauterine device (IUD) with women
      who are not using any modern contraceptive method in a family planning setting in
      Trabzon, Turkey. A great majority of all women in both groups were housewives and
      all indicated their husbands as the first and only lifetime sexual partner. The
      IUD user group (n = 211) did not differ significantly from the nonuser group (n =
      155) in terms of mean age, years of schooling, first age at intercourse,
      frequency of sexual intercourse or practice of vaginal douching (p >0.05). STD
      signs and symptoms were not found to be significantly different among both
      groups, with the exception of vaginal discharge. IUD users complained more of
      abnormal vaginal discharge than nonusers (RR = 2.09, CI = 1.17-3.75, p = 0.007).
      Bacterial vaginosis was diagnosed with the Gram-staining of the vaginal smear and
      current IUD users were found to be 2.78 times more likely to be diagnosed with
      bacterial vaginosis as compared to nonusers (p <0.00). The diagnosis of
      trichomoniasis, N. gonorrhea, vulvovaginal candidiasis, and Chlamydia was not
      found to be associated with IUD use.

PMID- 10958879
TI  - The incidence of actinomyces-like organisms in Papanicolaou-stained smears of
      copper- and levonorgestrel-releasing intrauterine devices.
AB  - Actinomyces-like organisms (ALOs) are a common finding in Papanicolaou-stained
      cervico-vaginal smears (PAP smears) of women using an intrauterine device (IUD).
      The incidence of ALOs positive PAP smears depends on the type of IUD. Pelvic
      actinomycosis is a severe disease that may require hysterectomy and salpingo
      oophorectomy. In a retrospective study we compared the incidence of ALOs positive
      PAP smears in users of the new levonorgestrel-releasing intrauterine device (LNG
      IUD) (n = 52) with the incidence in Multiload Copper IUD (ML375) users (n = 104).
      All IUDs had been inserted from 1996-1998. Women with a follow-up period of more
      than 9 months were included into the final analysis (LNG-IUD: n = 34; ML375: n =
      65). The incidence of ALOs in LNG-IUD users (2.9%) was significantly lower than
      in ML375 users (20%). Clinical consequences of ALOs positive PAP smears are
      discussed controversially. The low incidence in the LNG-IUD users probably leads
      to less IUD-removals, reinsertions and less pelvic-inflammatory-diseases.

PMID- 10958880
TI  - Acceptability evaluation of a natural rubber latex, a polyurethane, and a new non
      latex condom.
AB  - After more than a century of reliance on latex condoms, male condoms fabricated
      from new materials are finally becoming commercially available to consumers. This
      study was an open label acceptability study that compared three lubricated condom
      products during vaginal intercourse: a natural rubber latex condom, a
      polyurethane condom, and a new non-latex (styrene ethylene butylene styrene,
      SEBS) condom. Fifty-four couples who were using condoms for birth control were
      enrolled in this three-way crossover study. Each couple tested three condoms of
      each type in a randomized sequence. Couples reported condom performance after
      each use and rated condom acceptability after use of three condoms of each type.
      At the completion of the study, participants selected their preferred condom type
      for overall acceptability, sensitivity, ease of use, appearance, and comfort. All
      three condom types had low clinical breakage and slippage rates (</= 3.3%)
      although the polyurethane condom did not perform as well in other measures of
      performance including unrolling, discomfort, stretching, bunching, and sliding
      along the penis during intercourse. None of the condom types were statistically
      preferred overall [males: natural rubber latex 37%, polyurethane 24%, new non
      latex (SEBS) 37%, no preference 2%; females: natural rubber latex 33%,
      polyurethane 27%, new non-latex 37%, no preference 2%]. A statistically higher
      proportion of couples preferred both the natural rubber latex condom and the new
      non-latex condom above the polyurethane condom for ease of unrolling, and the
      natural rubber latex condom above the other condom types for perceived safety.
      Approximately two-thirds of both male and female participants preferred one of
      the two condoms made of synthetic materials suggesting that consumers will
      appreciate the availability of these products.

PMID- 10958881
TI  - Pregnancy rates among Chilean women who had non-surgical sterilization with
      quinacrine pellets between 1977 and 1989.
AB  - We describe cumulative pregnancy probabilities among women who underwent
      quinacrine pellet sterilization in Chile between 1977 and 1989 (N = 1492). We
      interviewed the women or relatives in 1991-93 and 1994-96, and reviewed hospital
      records. Mean follow-up was 9.6 years (median 9 years). We recorded 120
      pregnancies, including 40 that went to term or near-term. There were nine adverse
      outcomes in eight infants: one fetal death at 18 weeks gestation; three infants
      born prematurely; one stillbirth (placental infarct); and four infants with birth
      defects. There was no clustering of any particular kind of birth defect. For two
      insertions, the 10-year cumulative pregnancy probability was 8.9 (95% confidence
      interval 3. 7, 14.1). For 3 insertions, the 10-year rate was 7.0 (4.4, 9.5). For
      women who were under 35 years at insertion, the 10-year rate was 10. 7 (7.4,
      14.1). For women who were 35 or older at insertion, the 10-year rate was 3.1
      (0.6, 5.7). The pregnancy rate varied little for 2 vs. three insertions, but the
      rate did vary significantly by age, with women who received quinacrine at 35
      years or older 0.3 (0. 2, 0.5) times as likely to become pregnant as younger
      women. The 10-year cumulative ectopic pregnancy probabilities for women with two
      and three insertions of quinacrine were 0.9 (<0.1, 2.6) and 0.5 (<0.1, 1.2),
      respectively. Pregnancy rates after quinacrine insertion are higher than after
      surgical sterilization, but ectopic pregnancy rates appear similar.

PMID- 10958883
TI  - Impact of subdermal norgestrel on hepatic acyl-coenzyme A:cholesterol-
      acyltransferase (ACAT) activity: possible antiatherogenic effect.
AB  - The impact of subdermally placed ethinyl estradiol, norgestrel, and the
      combination of the two on cholesterol metabolism as measured by hepatic
      acyl:cholesterol-acyltransferase (ACAT) activity was examined in the rat model. A
      total of 48 rats were assigned to one of 6 groups, receiving either 0.1 mg or 1.0
      mg of ethinyl estradiol daily, 1.0 or 10 mg of norgestrel daily, and combinations
      of either 0.1 mg ethinyl estradiol/1.0 mg norgestrel or 1.0 mg ethinyl
      estradiol/10 mg norgestrel daily. All drugs were administered through subdermally
      placed time release capsules. The administration of norgestrel only in either 1.0
      mg or 10 mg resulted in significantly lower rates of ACAT activity (0.77 +/-
      0.566 and 0.91 +/- 0.239 pmol/mg/min, respectively). The combination of 1.0
      ethinyl estradiol and 10 mg norgestrel resulted in a significant increase in ACAT
      activity to 2.17 +/- 0.873. This combination also resulted in significantly
      greater weight loss at the conclusion of treatment [247.83 +/- 6.2 g (pre) vs.
      205.50 +/- 10.6 (post)]. There were no other differences in ACAT activity between
      groups and no other differences in weight, both between groups and pre- and post
      treatment within groups. In summary, subdermally placed norgestrel resulted in a
      significant lowering of ACAT activity not seen with either administration of
      ethinyl estradiol alone or the combination of ethinyl estradiol and norgestrel in
      doses ranging from 0.1 to 1.0 mg of ethinyl estradiol and 1.0 to 10.0 mg of
      norgestrel. Significantly increased ACAT activity for the combination of 1.0
      ethinyl estradiol and 10 mg norgestrel over either ethinyl estradiol or
      norgestrel alone or a lower dose combination suggests a dose-related threshold
      and drug-drug interaction for this effect. These results suggest that subdermally
      placed norgestrel may result in significantly lower ACAT activity and may have a
      potential role as an antiatherogenic treatment.

PMID- 10958882
TI  - Depressive symptoms in users and non-users of depot medroxyprogesterone acetate.
AB  - To evaluate the possible effects of depot medroxyprogesterone acetate (DMPA)
      injectable contraception on depressive symptoms, we conducted a population-based
      prospective study with women aged 18-39 years old enrolled at a health
      maintenance organization. At baseline, 183 women used DMPA and 274 were non
      users. Data on depressive symptoms and on factors potentially related to DMPA use
      and depression were collected by questionnaire at 6-month intervals for up to 3
      years. In multivariate longitudinal analysis, we found an increased likelihood of
      reporting depressive symptoms among continuous DMPA users (OR = 1.44; 95% CI =
      1.00-2.07) and discontinuers (OR = 1.60; 95% CI = 1.03-2.48) when compared to non
      users. Women who discontinued DMPA use had elevated depressive symptoms prior to
      discontinuation (OR = 2.30; 95% CI = 1.42-3.70) and immediately following
      discontinuation (OR = 2.46; 95% CI = 1. 46-4.14), and depressive symptoms
      subsided at subsequent visits relative to non-users. Our prospective analyses
      found an association between DMPA use and depressive symptoms but further
      research is needed to determine whether the relationship is causal.

PMID- 10958884
TI  - Copper corrosion-simulated uterine solutions.
AB  - We studied the copper corrosion and product layers originating in a simulated
      uterine solution at pH values 6.3 and 8.0 for 15, 65, 180, and 360 days at 37
      degrees C. Absorbance measurements were performed. Corrosion product layers on
      the copper surface were characterized by scanning electron microscopy, energy
      dispersive x-ray, and x-ray photo-electron spectroscopy techniques. Copper
      release for pH 6.3 and 8.0 was 3.4-4.5 microg/day for 15 days and 0.1-0.3
      microg/day for 360 days. Of the order of 30%-40% of dissolved cupric ions were
      trapped in the product layers. The main compounds identified were cuprite
      (Cu(2)O), calcite (CaCO(3)), and phosphates.

PMID- 10958885
TI  - Effect of local epididymal levonorgestrel on the fertilizing ability of male rat,
      a model for post-testicular contraception.
AB  - A thin levonorgestrel-silicone layer was applied on the capsule of the cauda
      epididymis of male rats to study a model for post-testicular male contraception.
      The effect of different levonorgestrel doses on the fertility of males was tested
      with fertile females. The time-dependent influence of a standard dose of
      levonorgestrel on serum LH and on testicular histology was estimated. Among the
      males tested, there was a group of animals where successful contraception with
      local application of levonorgestrel-silicone membrane was obtained. Sexual
      behavior was normal and the spermatogenesis was functioning, but the sperm were
      infertile. Although further research is needed to estimate adequate dose and
      strength of levonorgestrel in silicone matrix, this study shows that post
      testicular contraception is possible to achieve.

PMID- 10958886
TI  - Glycinergic potentiation by some 5-HT(3) receptor antagonists: insight into
      selectivity.
AB  - The ability of various 5-HT(3) receptor antagonists to potentiate spinal glycine
      responses was investigated. Whereas (3-alpha-tropanyl)-1H-indole-3-carboxylate
      (ICS 205930), (3-alpha-tropanyl)-3,5-dichlorobenzoate (MDL 72222) and 1-methyl-N
      (3-alpha-tropanyl)-1H-indazole-3-carboxamide (LY 278584) exhibited this property,
      even in identified motoneurones, several other chemically similar 5-HT(3)
      receptor antagonists did not. Introducing a methyl group on the nitrogen of the
      azabicyclo moiety of ICS 205930 greatly reduced the ability to potentiate glycine
      responses. Neither endo-1-methyl-N-(9-methyl-9-azabicyclo[3.3. 1]non-3-yl)
      indazole-3-carboxamide (granisetron), differing from LY 278584 by an additional
      carbon in this cycle, nor 2beta-carbomethoxy-3beta-benzoyloxytropane (cocaine),
      1,2,3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)-methyl]-4H-carba zol
      4-one (ondansetron) and (S)-4-amino-N-(1-azabicyclo[2.2. 2]oct-3-yl)-5-chloro-2
      methoxy-benzamide ((S)-zacopride) could potentiate glycine responses. A
      pharmacophore model of the glycinergic potentiators was generated by molecular
      modelling using MDL 72222 as a template. According to this model, an aromatic
      ring, a carbonyl group and a tropane nitrogen atom are required for glycinergic
      potentiation, as previously described for 5-HT(3) receptor antagonism. However,
      the steric allowance at the glycine receptor site and the tridimensional
      arrangement of the pharmacophoric elements appear to be more restricted.

PMID- 10958887
TI  - 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-induced egr-1 mRNA in rat
      brain: pharmacological manipulation.
AB  - Using in situ hybridization and immunohistochemical techniques, we examined the
      expression pattern of egr-1 mRNA and Egr-1 protein in several brain regions
      following administration of 3, 4-methylenedioxymethamphetamine (MDMA).
      Furthermore, we also studied the role of N-methyl-D-aspartate (NMDA) receptor,
      dopamine D(1) receptor, 5-hydroxytryptamine (5-HT) transporter or 5-HT(2A)
      receptor in the induction of egr-1 mRNA by MDMA. Basal constitutive levels of egr
      1 mRNA were detected in control rat brains. A single administration of MDMA (10
      mg/kg) caused marked induction of egr-1 mRNA in the prefrontal cortex, striatum
      and hippocampal dentate gyrus. However, no changes in the egr-1 mRNA levels were
      detected in the CA1 region of hippocampus and occipital cortex after
      administration of MDMA (10 mg/kg). Furthermore, the expression of egr-1 mRNA in
      the prefrontal cortex, striatum and hippocampal dentate gyrus after
      administration of MDMA (10 mg/kg) was blocked significantly by pretreatment with
      NMDA receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]
      cyclohepten-5, 10-imine ((+)-MK801; 1 mg/kg), dopamine D(1) receptor antagonist
      SCH 23390 (1 mg/kg) or 5-HT uptake inhibitor paroxetine (5 mg/kg), but not by 5
      HT(2A) receptor antagonist SR46349B (5 mg/kg). However, high basal levels of Egr
      1 immunoreactivity in the rat brain were not altered by administration of MDMA
      (10 mg/kg). These results suggest that MDMA alters the expression of egr-1 mRNA
      in several regions of rat brain, and that the expression of egr-1 mRNA by MDMA in
      the prefrontal cortex, striatum and hippocampal dentate gyrus appears to be
      mediated, at least in part, by NMDA receptor, dopamine D(1) receptor and 5-HT
      transporter.

PMID- 10958888
TI  - Characterization of nicotinic acetylcholine receptor-mediated noradrenaline
      release from the isolated rat stomach.
AB  - We characterized nicotinic acetylcholine receptor-mediated noradrenaline release
      from the isolated, vascularly perfused rat stomach. The stomach was perfused via
      the coeliac artery with Krebs-Ringer solution at a constant flow rate of 4 ml per
      minute. Endogenous noradrenaline released into the perfusate was
      electrochemically measured using high-performance liquid chromatography.
      Nicotinic receptor agonists were applied once into the perfusion medium for 2 min
      and nicotinic receptor antagonists were administered throughout the experiments.
      The (-)-nicotine (3x10(-5) M)-induced noradrenaline release was abolished by
      tetrodotoxin and hexamethonium and partially blocked by dihydro-beta-erythroidine
      (up to 10(-5) M) (a relatively selective antagonist of alpha4beta2 nicotinic
      receptors) and abolished by mecamylamine (10(-5) M) (a relatively selective
      antagonist of alpha3beta4 nicotinic receptors), but not influenced by alpha
      bungarotoxin (3x10(-7) M) or alpha-conotoxin ImI (10(-6) M) (antagonists of
      alpha7 nicotinic receptors). (+/-)-Epibatidine (3x10(-7) M) (a very potent, but
      non-selective agonist) and (-)-cytisine (3x10(-4) M) (an agonist of beta4
      nicotinic receptors) effectively evoked the release of noradrenaline, while (E)-N
      methyl-4-(3-pyridinyl)-3-butene-1-amine (RJR-2403) (up to 10(-4) M) (an agonist
      of alpha4beta2 nicotinic receptors) had no effect. The potency of these agonists
      was as followed; (+/-)-epibatidine>>(-)-nicotine>(-)-cytisine>>>RJR -2403. These
      results are compatible with the published view that alpha3beta4 nicotinic
      receptors are predominant in other parts of the autonomic nervous system. These
      receptors (probably located on the gastric sympathetic ganglia) are involved in
      the release of noradrenaline from the rat stomach.

PMID- 10958889
TI  - Differential effects of response-contingent and response-independent nicotine in
      rats.
AB  - Passive administration of nicotine activates the hypothalamic-pituitary
      adrenocortical axis and sympathetic nervous system. However, little is known
      about the effects of self-administered nicotine. Drug-naive rats were trained to
      respond for food reinforcement and then tested in one, 1-h session in which they
      received response-contingent i.v. nicotine or response-independent i.v. nicotine
      or saline. Blood draws were taken immediately prior to the session, 15 min after
      the first infusion and immediately after the session. Both response-contingent
      and response-independent nicotine (RI/N) increased corticosterone within 15 min,
      however, corticosterone levels returned to baseline in animals receiving response
      contingent nicotine (RC/N) by the end of the session while remaining elevated in
      those receiving RI/N. Furthermore, only RI/N increased plasma epinephrine and
      norepinephrine levels; RC/N produced no effect. These differences indicate that
      nicotine's acute effects are powerfully modified by the presence of a contingency
      relationship between drug administration and the animal's behavior and that this
      relationship develops very rapidly.

PMID- 10958890
TI  - Muscarinic receptor agonists decrease cocaine self-administration rates in drug
      naive mice.
AB  - (5R,6R)-6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[ 3.2.1]octane (PTAC)
      is a selective muscarinic receptor ligand. The compound exhibits high affinity
      for central muscarinic receptors with partial agonist mode of action at
      muscarinic M(2) and M(4) and antagonist mode of action at muscarinic M(1), M(3)
      and M(5) receptor subtypes. The compound was earlier reported to exhibit
      functional dopamine receptor antagonism in rodents despite its lack of affinity
      for dopamine receptors. In the present study, we report that PTAC, as well as the
      muscarinic receptor agonists pilocarpine and oxotremorine, dose-dependently
      decreased rates of intravenous self-administration (fixed ratio 1) of the
      indirect dopamine receptor agonist cocaine in drug naive mice. Similar decreases
      in cocaine self-administration rates were obtained with the dopamine receptor
      antagonists olanzapine, clozapine, risperidone, fluphenazine and haloperidol.
      These findings suggest that compounds with partial muscarinic receptor agonist
      mode of action may be used in the medical treatment of cocaine abuse.

PMID- 10958891
TI  - A nitric oxide synthase inhibitor reduces hyperphagia induced in rats by the 5
      HT(1A) receptor agonist, 8-OH-DPAT, independently of hypothalamic serotonin
      metabolism.
AB  - In rats, a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl
      ester (L-NAME) inhibited the hyperphagia induced by the 5-hydroxytryptamine (5
      HT)(1A) autoreceptor agonist, 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT).
      8-OH-DPAT reduced 5-HT metabolism in the hypothalamus, and this was not blocked
      by pretreatment with L-NAME. L-NAME also did not affect basal hypothalamic 5-HT
      metabolism or reverse the decreases in 5-HT synthesis in hypothalamus. These
      results suggest that the hypophagic effects of L-NAME, which inhibits NO
      formation, are independent of 5-HT metabolism in the hypothalamus.

PMID- 10958892
TI  - Effects of sigma(1) receptor ligand, MS-377 on apomorphine- or phencyclidine
      induced disruption of prepulse inhibition of acoustic startle in rats.
AB  - To evaluate the antipsychotic property of a sigma(1) receptor ligand, (R)-(+)-1
      (4-chlorophenyl)-3-?4-(2-methoxyethyl)piperazin-1-yl? methyl-2-pyrrolidinone-L
      tartrate (MS-377), an antagonistic effect of MS-377 on the disruption of prepulse
      inhibition (PPI) of the acoustic startle by apomorphine or phencyclidine (PCP)
      was investigated in rats. MS-377 antagonized the PCP-induced disruption of PPI.
      The ED(50) value of MS-377 for this effect was 0.66 mg/kg. In contrast,
      apomorphine-induced disruption of PPI was not attenuated by MS-377. These data
      indicate that the PCP-induced disruption of PPI in rats would be, at least
      partially, mediated by sigma receptors and MS-377 could be a novel anti-psychotic
      agent with clinical efficacy for the sensorimotor-gating deficit in
      schizophrenia.

PMID- 10958893
TI  - Amrinone reduces ischaemia-reperfusion injury in rat heart.
AB  - We investigated the effects of amrinone on ischaemia-induced changes in
      myocardial function in isolated rat hearts. Isolated hearts from male Sprague
      Dawley rats (150-275 g) were perfused with physiological salt solution at a
      constant flow rate. The effects of amrinone (30 microM) on left ventricular end
      diastolic pressure, positive and negative dP/dt, heart rate and coronary
      perfusion pressure were observed following global ischaemia and reperfusion. In
      normal hearts, amrinone had no effect on myocardial contractility, heart rate,
      coronary perfusion pressure or left ventricular end diastolic pressure. Ischaemia
      reperfusion caused an increase in coronary perfusion pressure, left ventricular
      end diastolic pressure and creatine kinase outflow and amrinone (present from
      before ischaemia) decreased the rise in all of these parameters. However, when
      amrinone was added only after the ischaemia, it had no effect on coronary
      perfusion pressure or left ventricular end diastolic pressure. Thus, the effect
      on coronary perfusion pressure must be due to actions during the ischaemia phase.
      We suggest that amrinone has pharmacological properties which may be useful in
      reducing ischaemia-reperfusion injury. We speculate that this involves altering
      ischaemia-induced changes in intracellular Ca(2+) in the myocytes.

PMID- 10958894
TI  - Anti-arrhythmic effects of levcromakalim in the ischaemic rat heart: a dual
      mechanism of action?
AB  - The action of pharmacological openers of K(ATP) channels depends on the
      availability and levels of various intracellular nucleotides. Since these are
      subject to change during myocardial ischaemia, K(ATP) channel openers may affect
      ischaemic and non-ischaemic tissue differentially. Using a recently developed
      dual coronary perfusion method, we investigated the effects on arrhythmias of the
      prototypical K(ATP) channel opener levcromakalim when applied selectively to
      ischaemic and/or non-ischaemic tissue. A novel perfusion cannula was used to
      independently perfuse the left and right coronary beds of hearts isolated from
      rats. Selective infusion of levcromakalim (3, 10 or 30 microM) into the left
      coronary bed in the absence of ischaemia did not induce ventricular arrhythmias.
      Regional zero-flow ischaemia was induced by cessation of flow to the left
      coronary bed and hearts received levcromakalim selectively into either the left,
      right, or both coronary beds. When applied selectively to the ischaemic left
      coronary bed, levcromakalim (3, 10 or 30 microM; n=10/group) delayed the onset of
      ventricular tachycardia in a dose-dependent manner (by 21*, 43* and 112%* at 3,
      10 and 30 microM; *P<0.05 vs. control). When applied only to the non-ischaemic
      right coronary bed, levcromakalim reduced the incidence of ventricular
      tachycardia during later phases of ischaemia (from 100% in controls to 30%*).
      When present in both coronary beds, levcromakalim had a striking anti-arrhythmic
      effect--the overall incidence of ventricular tachycardia being reduced from 100%
      in controls to 20%*. We conclude that levcromakalim may have an anti-arrhythmic
      effect when applied either to ischaemic or non-ischaemic tissue but that the
      mechanisms may differ depending on the metabolic state of the heart.

PMID- 10958895
TI  - Effects of the second-generation leukotriene B(4) receptor antagonist,
      LY293111Na, on leukocyte infiltration and collagen-induced arthritis in mice.
AB  - The effects of the second-generation leukotriene B(4) receptor (LTB(4) receptor)
      antagonist, 2-[2-propyl-3-?3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxy-phenoxy]-propo
      xy?phenoxy]benzoic acid sodium salt (LY293111Na), on leukotriene B(4)-induced
      leukocyte infiltration and interleukin-1-accelerated collagen-induced arthritis
      in mice were studied. Neutrophil infiltration induced into an air pouch by
      leukotriene B(4) was dose-dependently inhibited by LY293111Na and strongly so by
      another LTB(4) receptor antagonist, 4-[5-?4-(aminoiminomethyl)phenoxy?pentoxy]-3
      methoxy-N, N-bis(1-methylethyl) (Z)-2butenedioate (1:1) (CGS25019C). Both
      compounds significantly inhibited the increase of the arthritis index and the
      ankle bone destruction in interleukin-1-accelerated collagen-induced arthritis.
      Phenidone, a 5-lipoxygenase inhibitor, also inhibited interleukin-1-accelerated
      collagen-induced arthritis, while indomethacin and tenidap, cyclooxygenase
      inhibitors, had slight inhibitory effects. Injection of interleukin-1 elicited a
      marked increase of the leukotriene B(4) level in arthritic paws, while the
      prostaglandin E(2) level was slightly increased. These findings indicate clearly
      that leukotriene B(4) is an important mediator of interleukin-1-accelerated
      collagen-induced arthritis in mice. If this can be extrapolated to man, LTB(4)
      receptor antagonists might be useful for treatment of the acute progressive phase
      of human arthritis.

PMID- 10958896
TI  - Effect of TEI-9874, an inhibitor of immunoglobulin E production, on allergen
      induced asthmatic model in rats.
AB  - As TEI-9874, 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)ben zoic acid
      reduces allergen-specific immunoglobulin E (IgE) production by human peripheral
      blood mononuclear cells in vitro, we evaluated its potency on an allergen-induced
      asthmatic model in Brown-Norway rats. Inhaled ovalbumin induced the immediate
      phase asthmatic response, the late-phase asthmatic response, the infiltration of
      leukocytes into bronchoalveolar lavage fluid, and an increase of serum anti
      ovalbumin IgE. These parameters were suppressed by the treatment with TEI-9874
      (3, 10, and 30 mg/kg p.o.). The ovalbumin-induced airway hyperresponsiveness was
      prevented by TEI-9874 (30 mg/kg p.o.). Furthermore, the suppression of the
      immediate-phase asthmatic response and the late-phase asthmatic response by TEI
      9874 was almost completely extinguished by the exogenous administration of rat
      anti-ovalbumin antiserum. These results indicate that the efficacy of TEI-9874 on
      the asthmatic response is mainly mediated by the suppression of allergen-specific
      IgE production and TEI-9874 appears to be a good candidate as therapy for IgE
      mediated allergic asthma.

PMID- 10958897
TI  - The lack of compound 48/80-induced contraction in isolated trachea of mast cell
      deficient Ws/Ws rats in vitro: the role of connective tissue mast cells.
AB  - In the rat trachea, two types of mast cells have been identified, connective
      tissue mast cells and mucosal mast cells. Their different characteristics may
      account for their different biological functions. The role of connective tissue
      mast cells in tracheal contraction as one feature of the immediate reaction of
      asthma was studied in vitro in isolated trachea, using tissue derived from mast
      cell-deficient (Ws/Ws) rats, heterozygous (Ws/+) rats and control (+/+) rats, and
      compound 48/80 as a potent inducer of mast cell degranulation. The contractile
      response of tracheas from the three types of rats was also studied upon exposure
      to the following spasmogens: histamine, 5-hydroxytryptamine (5-HT), and
      carbachol. Histamine content in tissues reflected the differing mast cell numbers
      in strips from the three rat types. It was found that carbachol and 5-HT elicited
      tracheal contraction in a similar manner in strips from the three types of rats.
      Histamine had no contractile effect. Compound 48/80, at a dose of 25 microg/ml,
      elicited contraction in tracheas from both control (+/+) and heterozygous (Ws/+),
      but not in trachea from Ws/Ws rats. Compound 48/80-induced contractions in
      tracheas from +/+ rats were inhibited by 0.1 microM ketanserin and 0.1 microM
      nedocromil, but not by 0.1 microM mepyramine. Enzyme histochemistry confirmed
      that the degranulation occurred in connective tissue mast cells, but not in
      mucosal mast cells. We concluded that connective tissue mast cells play an
      important role in rat tracheal contraction via 5-HT release induced by compound
      48/80. In addition, the specific mast cell-deficient (Ws/Ws) rats provide a good
      tool for studying the roles of mast cells in airway system.

PMID- 10958898
TI  - Estimating digestion rate and the problem of individual variability, exemplified
      by a scyphozoan jellyfish.
AB  - Short-term (h) and long-term (days) individual variability and the effects of
      momentary change in feeding intensity on digestion time were studied in the
      scyphomedusa Aurelia aurita as a basis for developing a method to experimentally
      measure the digestion rate with a high precision. Ten individual medusae showed
      only small, non-significant differences in average digestion time (range, 2.1-2.5
      h at 10 degrees C) over a 9-day experiment, whereas variability within and
      between days and between individuals at a given occasion was high. When medusae
      were manually kept at a constant feeding intensity, stomach fullness showed high
      variability both between individuals and within an individual over time. With a
      feeding intensity of, respectively, 1, 2, 4 and 8 prey h(-1) over a 5-h
      experimental period, stomach fullness of most individuals corresponded to a
      theoretical digestion time of 1-3 h, whereas single meals of the same size
      usually gave somewhat higher digestion time. Medusae subject to a switching from
      a low to a high feeding intensity tended to increase the variability, but most
      individuals showed a digestion time of 1-3 h. An opposite switching tended to
      increase the digestion time and its variability. It is concluded that the
      digestion time of A. aurita is randomly variable over time within given limits
      for a given food and environmental condition. This variability is non
      synchronised in the population, causing high variability between individuals, and
      changes in the feeding intensity cause additional variability. However, the
      average digestion time of A. aurita in a physically and nutritionally stable
      environment is robust, and changes in the feeding intensity give predictable
      effects. The use of field collected data on stomach contents and laboratory
      determined digestion times is therefore an attractive method to calculate
      predation rate, but the inherent high variability in digestion time must be taken
      into consideration when designing the digestion experiments. Based on these
      findings a simple experimental method to determine the digestion time of aquatic
      animals is outlined and evaluated. The digestion time is simply given as the
      ratio between number of prey in stomach and total number of prey eaten, times the
      incubation time, assuming that the feeding intensity is constant.

PMID- 10958899
TI  - Predator-prey relations between age-1+ summer flounder (Paralichthys dentatus,
      Linnaeus) and age-0 winter flounder (Pseudopleuronectes americanus, Walbaum):
      predator diets, prey selection, and effects of sediments and macrophytes.
AB  - Laboratory experiments and weekly trammel net surveys in the Navesink River, New
      Jersey (USA) were used to examine the predator-prey interaction between age-1+
      summer flounder (Paralichthys dentatus) and age-0 winter flounder
      (Pseudopleuronectes americanus). Winter flounder (24-67 mm TL) were the dominant
      piscine prey of summer flounder (n=95, 252-648 mm TL) collected in trammel nets.
      We observed a temporal shift in summer flounder diets from sand shrimp (Crangon
      septemspinosa) and winter flounder, dominant during June and early July, to blue
      crabs (Callinectes sapidus) and other fishes (primarily Atlantic silversides,
      Menidia menidia and Atlantic menhaden, Brevortia tyrannus) later in the summer.
      Variations in prey selection appeared to be related to changes in the spatial
      distribution of predators and spatio-temporal variation in prey availability. In
      laboratory experiments, summer flounder (271-345 mm total length, TL) preferred
      demersal winter flounder to a pelagic fish (Atlantic silversides) and a benthic
      invertebrate (sand shrimp) prey, and the vulnerability of winter flounder
      increased with increasing prey body size from 20 to 90 mm TL. Experiments testing
      habitat effects showed that mortality of winter flounder in three different size
      classes (20-29, 40-49, 60-69 mm TL) was not influenced by sediment grain sizes
      permitting differential burial of the prey. However, vegetation enhanced
      survival, with fish suffering lower mortality in eelgrass (Zostera marina, 15+/
      0.04%) than in sea lettuce (Ulva lactuca, 38+/-0.04%) or bare sand (70+/-0.07%)
      when the macrophytes were planted to produce similar leaf surface areas (5000
      cm(2) m(-2)). Prey vulnerability appeared to be related to the role of vision in
      the predator's attack strategy and prey activity levels.

PMID- 10958900
TI  - Fragmentation in the branching coral Acropora palmata (Lamarck): growth,
      survivorship, and reproduction of colonies and fragments.
AB  - Acropora palmata, a branching coral abundant on shallow reef environments
      throughout the Caribbean, is susceptible to physical disturbance caused by
      storms. Accordingly, the survivorship and propagation of this species are tied to
      its capability to recover after fragmentation. Fragments of A. palmata comprised
      40% of ramets within populations that had experienced recent storms. While the
      survivorship of A. palmata fragments was not directly related to the size of
      fragments, removal of fragments from areas where they settled was influenced by
      size. Survivorship of fragments was also affected by type of substratum; the
      greatest mortality (58% loss within the first month) was observed on sand,
      whereas fragments placed on top of live colonies of A. palmata fused to the
      underlying tissue and did not experience any losses. Fragments created by
      Hurricane Andrew on a Florida reef in August 1992 began developing new growth
      (proto-branches) 7 months after the storm. The number of proto-branches on
      fragments was dependent on size, but growth was not affected by the size of
      fragments. Growth-rates of proto-branches increased exponentially with time (1.7
      cm year(-1) for 1993-1994, 2.7 cm year(-1) for 1994-1995, 4.2 cm year(-1) for
      1995-1996, and 6.5 cm year(-1) for 1996-1997), taking over 4 years for proto
      branches to achieve rates comparable to those of adult colonies on the same reef
      (6.9 cm year(-1)). In addition to the initial mortality and reduced growth-rates,
      fragmentation resulted in a loss of reproductive potential. Neither colonies that
      experienced severe fragmentation nor fragments contained gametes until 4 years
      after the initial damage. Although A. palmata may survive periodic fragmentation,
      the long-term effects of this process will depend ultimately on the balance
      between the benefits and costs of this process.

PMID- 10958901
TI  - Analysis of behavioural rejection of micro-textured surfaces and implications for
      recruitment by the barnacle Balanus improvisus.
AB  - Experiments performed in the field and in the laboratory show that the barnacle,
      Balanus improvisus, preferentially settles on smooth surfaces. Settlement and
      recruitment of B. improvisus was evaluated on micro-textured surfaces with scales
      of surface texture ranging from 1 to 100 um in profile heights. Surface texture
      with profile heights within a topographic range of 30-45 um reduced settlement
      and recruitment by 92% as compared to smooth surfaces. The reduction in
      recruitment on micro-textured surfaces is best explained by behavioural responses
      to surface topography. Behavioural experiments show that cyprids have a higher
      propensity for smooth surfaces than for micro-textured surfaces. Cyprids spend
      more time exploring smooth surfaces and more time swimming when exposed to micro
      textured surfaces. Micro-textured surfaces are more often rejected by cyprids
      after exploration than smooth surfaces. It is suggested that some scales of
      surface texture could be exploited to improve future anti-fouling techniques in
      geographical areas where Balanus improvisus is a severe fouling problem.

PMID- 10958902
TI  - The respiratory performance and survival of the bivalve Macoma balthica (L.) at
      the southern limit of its distribution area: a translocation experiment.
AB  - The hypothesis was tested that animals near their extreme Southern limits, due to
      high temperatures, have a high respiration rate, whereby they reach an extreme
      low weight-index and ultimately disappear. At estuarine stations the respiration
      rate of Macoma balthica (L.) (Baltic clam) did not show interseasonal changes,
      indicating seasonal acclimation, but within the season the respiration increased
      with increasing temperature, indicating the absence of short-term acclimation. In
      clams translocated from the Netherlands towards the Bidasoa estuary, 200 km South
      of their Southern distribution limit, their respiration rate was higher and
      weight-index lower than in specimens living in Dutch estuaries. Irrespective of
      an effect of the temperature, clams exposed in experiments to water from Bidasoa
      showed a higher respiration than clams exposed to water from the other stations.
      Moreover, at non-estuarine stations with a low food content, the clams showed
      reversed acclimation, i.e., the respiration rates in winter were much lower than
      summer rates, most probably a strategy to conserve energy by means of a depressed
      metabolism. A weight index of 5 mg DW/cm(3) and glycogen content of 2% DW are
      suggested as the minimal values below which the metabolic energy balance of
      Baltic clams becomes more negative and the clam population disappears. It was
      concluded that factors other than temperature influenced the respiration and
      weight-index of clams, and hence their presence or absence, e.g., food
      concentration, innate seasonal cycles, and possible pollutants in the water.

PMID- 10958903
TI  - Chemical and physical defenses of Singapore gorgonians (Octocorallia:
      Gorgonacea).
AB  - Gorgonians are abundant in tropical waters and their polyps are seldom predated
      on. This study investigates how gorgonians defend themselves chemically and
      physically against fish predation. Gorgonian extracts and sclerites were
      incorporated into fish feed and tested on reef fishes. Laboratory bioassays using
      Greyhead wrasses, Halichoeres purpurescens, as well as field bioassays showed
      five gorgonian species from the family Ellisellidae and three from the family
      Plexauridae collected from Singapore reefs to be deterrent towards fishes.
      Bioassays of fractions obtained from subsequent fractionation suggested
      synergistic or additive effects between compounds present in gorgonians.
      Sclerites incorporated into fish feed in their natural concentrations were also
      tested for fish deterrence and were positive for only two gorgonian species from
      the family Ellisellidae.

PMID- 10958904
TI  - Competitive dominance by tabular corals: an experimental analysis of recruitment
      and survival of understorey assemblages.
AB  - Tabular and staghorn corals of the genus Acropora often form low-diversity stands
      on shallow coral reefs, presumably due to their rapid growth rate and ability to
      outcompete understorey assemblages. Coral cover underneath the abundant Indo
      Pacific tabular coral, Acropora hyacinthus, was four times lower than on the
      adjacent substratum on the reef crest at Lizard Island on the northern Great
      Barrier Reef. We investigated the effect of A. hyacinthus on patterns of
      recruitment and mortality by placing experimental panels and coral fragments
      underneath large colonies of A. hyacinthus. After 8 weeks, recruitment of corals,
      filamentous algae and crustose coralline algae (CCA) underneath A. hyacinthus was
      96, 85 and 50% lower, respectively, compared to panels placed in the open. In
      contrast, recruitment by bivalves and polychaetes was uniform among treatments,
      while bryozoans recruited four times more abundantly under A. hyacinthus than in
      the open. Consequently, the low rate of recruitment by corals beneath A.
      hyacinthus does not appear to be due to a reduction in the delivery of larvae
      underneath tables. Instead, the disparity between phototrophic and heterotrophic
      taxa suggests that diminished light levels under A. hyacinthus are partially
      responsible for the divergence in recruit assemblages. To test the effect of A.
      hyacinthus on early mortality and growth of established organisms, recruitment
      panels were placed on the open for 9 weeks then transplanted underneath A.
      hyacinthus for a further 8 weeks. The survivorship of juvenile corals underneath
      tables was less than half that of those on control panels on the unshaded reef
      crest. Furthermore, the abundance of algal turfs and CCA was sharply lower on
      transplanted panels. In contrast, heterotrophic organisms increased in cover,
      regardless of treatment. Experimental branch fragments of Acropora intermedia and
      Pocillopora damicornis also survived poorly following transplantation underneath
      A. hyacinthus, compared to adjacent, unshaded controls. We conclude that A.
      hyacinthus is a formidable competitor which can kill neighbouring corals by
      overgrowing them, and pre-empt future competition by reducing coral recruitment.

PMID- 10958905
TI  - A new illusion demonstrates long-range processing.
AB  - In the Fraser phase-illusion [Popple & Sagi. Vision Research, 40 (2000) 873-878]
      rows of Gabor patches appear tilted because successive elements are shifted in
      phase. We measured this bias in global orientation judgment, while varying the
      number of patches in each row, and their separation. We found that illusory tilt
      increases with the number of patches, at least up to ten patches for a separation
      of four carrier periods. This finding implies that the visual system is able to
      integrate information over large (>10 degrees ) strips of the central visual
      field. Our model shows that the tilt illusion might be the result of averaging
      the activity of oriented filters.

PMID- 10958906
TI  - Monocular lustre from flicker.
AB  - A spot that flickers at 16 Hz between two luminance levels (on a grey surround)
      has an appearance of metallic lustre, which we call 'monocular lustre'. Binocular
      and monocular lustre were measured in comparable conditions by a rating
      procedure, and both were reported only when the light and dark values of the
      flickering (or binocularly fused) spot straddled the surround luminance, so that
      the spot was alternately brighter and darker than the surround. We attribute
      lustre to competition between ON and OFF visual pathways.

PMID- 10958907
TI  - Separate simultaneous processing of egocentric and relative positions.
AB  - It is well established that all kinds of visual attributes are processed
      separately within the brain. This separation is related to differences in the
      information that is relevant for the different attributes. When attributes differ
      greatly (such as colour and motion) it is obvious that they must rely on
      different information. However, separating the processing of different attributes
      could also allow highly related attributes to evolve independently, so that they
      end up being judged on the basis of different types of information. Here, we
      examine the case of egocentric and relative localisation. For judging egocentric
      positions, the orientation of the eyes has to be taken into account. This is not
      so for judging relative positions. We demonstrate that these two attributes can
      be processed separately by showing that simultaneous judgements of relative and
      egocentric position differ in their dependency on eye orientation. Subjects
      pursued a moving dot. We flashed either single targets, or pairs of targets with
      a 67 ms interval between them, directly below the subjects' gaze. As the eyes
      were moving during the 67 ms interval, the retinal separation between pairs of
      targets was different from their actual separation. Subjects indicated the
      position at which they saw the targets with reasonable reproducibility, with a
      consistent bias in the direction of the eye movement. However, when two targets
      were flashed, the indicated separation between them usually coincided with their
      retinal separation, rather than with their actual separation. We conclude that
      egocentric and relative spatial positions can be estimated separately and
      simultaneously, on the basis of different types of information.

PMID- 10958908
TI  - Motion in depth based on inter-ocular velocity differences.
AB  - Two different binocular cues are known for detecting motion in depth. One is
      disparity change in time and the other is inter-ocular velocity difference. In
      contrast to the well known fact of the use of the disparity cues, no evidence of
      contribution of inter-ocular velocity differences for detecting motion in depth
      has been reported. We demonstrate that motion in depth can be seen based solely
      on inter-ocular velocity differences using binocularly uncorrelated random-dot
      kinematograms. This indicates that the visual system uses monocular velocity
      signals for processing motion in depth in addition to disparity change in time.

PMID- 10958909
TI  - Cone inputs to murine retinal ganglion cells.
AB  - Responses of single retinal ganglion cells in different areas of mouse retina
      were studied to determine their cone inputs, using spectral sensitivity functions
      and chromatic adaptation. Spectral sensitivity curves were based on threshold
      response criteria to full field stimulation. The retina of the mouse was viewed
      through a dilated pupil with a surgical microscope. Ganglion cells were
      classified into three groups: one receiving inputs from short wave sensitive
      cones, a second receiving inputs from only middle wavelength sensitive cones and
      a third receiving inputs from both of these types of cones. The ventral retina,
      contained a large fraction of the first group of ganglion cells. The dorsal
      retina and the border between these two areas contained relatively more of the
      latter two groups. A small fraction of cells were found which displayed
      antagonistic-like interactions between photoreceptor systems. The results
      demonstrate that single ganglion cells in mouse retina can select responses from
      only one of the two cone mechanisms present in this retina, even in areas
      containing both types of cones.

PMID- 10958910
TI  - Interactions between flicker thresholds and luminance pedestals.
AB  - We investigated the interactions between flicker thresholds and luminance
      pedestals using threshold versus contrast (TvC) and method of constant stimuli
      paradigms. High amplitude luminance pedestals were found to elevate flicker
      thresholds, but low amplitude luminance pedestals were unable to reduce flicker
      thresholds. Luminance pedestals elevated flicker thresholds more at low temporal
      frequencies. A simple model based on local light adaptation was able to capture
      the general form of the TvC functions. Our results suggest that flicker
      thresholds derived in the presence of a luminance pedestal (luminance-pedestal
      flicker) may vary from those obtained by modulating about a mean luminance (mean
      modulated flicker).

PMID- 10958911
TI  - Seven experiments on pattern vision of the honeybee, with a model.
AB  - When vertically presented patterns are fixed in relation to the point of choice
      of the bees, the locations of areas of colour or black can be discriminated in
      the vertical direction, and in the horizontal direction when the bees use some
      mark with green contrast on which to stabilize. The bees can fixate on a radial
      pattern, a spot, or a ring of spots. Resolution depends on fixation, which
      depends on green contrast, but the discrimination of locations then depends on
      the photon flux at green and blue receptors. The model proposes that, when the
      eye is stabilised, a tonic channel from all receptor types is activated in the
      region of the eye that looks at the cue. This channel generates a perceptual
      space in which location, colour and size contribute to a signature for each cue
      in each eye. In other channels of processing, the stimulus is the phasic
      modulation of green receptors by edges, and these pathways are colour blind. When
      the patterns are composed of bars, the cues are the radial and tangential edges
      and the integrated edge orientation, irrespective of shuffling of locations on
      the target. Orientation can be detected in fuzzy edges with a gradient of black
      to white over about 60 degrees subtended from the point of choice. These cues
      correspond to the response profiles of large-field, phasic, coarsely tuned
      filters. There is no evidence that cues from edges have a spatial tag. The model
      also proposes that each filter for average orientation, or radial or tangential
      edges, corresponds to an ascending succession of phasic neurones. Each processing
      channel generates a perceptual space where combinations of related cues form
      signatures, and at least one signature is passed to memory as an index item. A
      pattern may generate several signatures but patterns are discriminated only when
      their signatures differ. In the bee there is no evidence for the re-assembly of
      the pattern.

PMID- 10958912
TI  - Independent mechanisms produce visually perceived eye level (VPEL) and perceived
      visual pitch (PVP).
AB  - Two aspects of the perception of extrapersonal space undergo systematic changes
      with variations in the pitch of the visual environment: (1) the physical
      elevation perceived to correspond to eye level (VPEL); and (2) the perception of
      the pitch of the visual environment (PVP). Thus, one might assume that both
      discriminations are controlled by a common mechanism utilizing visual information
      from the pitched surface. In fact this assumption has been made frequently, and -
      in different forms - underlies three substantial but very different historical
      streams in the literature. A quantitative theoretical development shows that two
      of these streams, although derived from very different viewpoints and appearing
      very different themselves (it is assumed that the basis for both PVP and VPEL is
      information about the pitch of the visual field in one, and information about the
      location of the subject's eye level within the visual field in the other), make
      identical predictions: each requires that the weighted sum of PVP and VPEL equal
      the magnitude of physical pitch and that the weighted sum of their first
      derivatives equal a constant. The third stream, which assumes that an internal
      representation of the visual field gives rise to both PVP and VPEL, requires that
      a weighted difference of PVP and VPEL be proportional to physical pitch and that
      the weighted difference of their derivatives equal a constant. In an experiment
      designed to examine the relation between VPEL and PVP, psychophysical
      measurements of VPEL and PVP were made on 20 subjects across a range of pitches
      from -30 degrees to +20 degrees. Contrary to the predictions from all three
      interpretations, we find no significant correlation between the two perceptual
      variables when the influence of pitch itself is removed, despite the fact that
      VPEL and PVP each increased systematically with increasing visual field pitch.
      The results not only rule out the specific predictions derived from all three
      historical streams, they also rule out any theoretical viewpoint that requires
      control of both perceptual responses by a single mechanism. The statistical
      independence between VPEL and PVP implies independence between the mechanisms
      that give rise to them. The correlation observed here and elsewhere between
      individual PVP and VPEL settings when the influence of the systematic variation
      of pitch is not eliminated is a consequence of the way in which variations in the
      two perceptions are generated experimentally, and not on an identity of the
      mechanisms mediating the generation of the two perceptual variables themselves.

PMID- 10958913
TI  - The functional role of oriented spatial filters in the perception of mirror
      symmetry--psychophysics and modeling.
AB  - We investigated human sensitivity to vertical mirror symmetry in noise patterns
      filtered for narrow bands of variable orientations. Sensitivity is defined here
      as the amount of spatial phase randomization corresponding to 75% correct
      performance in a 2AFC detection task. In Experiment 1, sensitivity was found to
      be high for tests patterns of all orientations except those parallel to the axis
      of symmetry. This implies that corresponding mirror-orientations (e.g. -45 and
      +45 degrees ) are combined prior to symmetry detection. In Experiment 2,
      observers detected symmetry in tests of variable orientation in the presence of
      either non-symmetric or symmetric masks filtered for orientations either parallel
      or perpendicular to the axis. Observers were found to be primarily affected by
      masks of the same orientation as the test, thus suggesting that symmetry is
      computed separately in distinct mirror-orientation channels. In Experiment 3,
      observers detected a symmetric test of variable height and width embedded in
      random noise. Data revealed that mirror symmetry is computed over a spatial
      integration region (IR) that remains approximately constant in area but whose
      height-to-width aspect ratio changes from 20:1 to 2:1 as orientation is varied
      from parallel to perpendicular to the axis. We compare human data against that of
      an ideal observer to identify key factors that limit visual performance and
      discuss the implications for the functional architecture of symmetry perception.
      We also propose a multi-channel model of symmetry detection that combines the
      output of oriented spatial filters in a simple and physiologically plausible
      manner. Particular emphasis is placed on the notion that changes in the shape of
      the IR with orientation compensate for changes in information density and
      partially equate performance across orientations.

PMID- 10958914
TI  - First- and second-order processing in transient stereopsis.
AB  - Large-field stimuli were used to investigate the interaction of first- and second
      order pathways in transient-stereo processing. Stimuli consisted of sinewave
      modulations in either the mean luminance (first-order stimulus) or the contrast
      (second-order stimulus) of a dynamic-random-dot field. The main results of the
      present study are that: (1) Depth could be extracted with both the first-order
      and second-order stimuli; (2) Depth could be extracted from dichoptically mixed
      first- and second-order stimuli, however, the same stimuli, when presented as a
      motion sequence, did not result in a motion percept. Based upon these findings we
      conclude that the transient-stereo system processes both first- and second-order
      signals, and that these two signals are pooled prior to the extraction of
      transient depth. This finding of interaction between first- and second-order
      stereoscopic processing is different from the independence that has been found
      with the motion system.

PMID- 10958915
TI  - Degraded illusory contour formation with non-uniform inducers in Kanizsa
      configurations: the role of contrast polarity.
AB  - The neuronal and computational mechanisms involved in illusory contour formation
      are thought to be sensitive to the orientation and magnitude of contrast at
      luminance discontinuities, but insensitive to the sign of contrast at such
      discontinuities. It is shown here that boundary formation in Kanizsa-type
      illusory figures exhibits sensitivity to the spatial distribution of inducing
      elements of opposite contrast polarity. Shape discrimination was used as an
      objective measure of the saliency of illusory figures, revealing pronounced
      degradation of illusory boundaries when contrast polarity reversed at the
      intersections of orthogonally oriented edges within each inducer. These results
      suggest the previously unsuspected importance of image properties related to
      environmentally relevant constraints in perception of illusory contours and
      occlusion.

PMID- 10958916
TI  - Occlusions and their relationship with the distribution of contrasts in natural
      images.
AB  - An Information-Theory-like hypothesis recently proposed for early visual
      processing (the Minimal Local-Asperity hypothesis) accounts for the adaptive
      behavior with intensity of horizontal cells. It has been shown that for this to
      hold, the probability that a point is traversed by an occluding border must
      increase supralinearly (that is, with a positive second derivative) as a function
      of contrast. We test this condition by analyzing the distribution of contrasts
      and their relationship with occluding borders in natural images. We find that the
      distribution of contrasts in natural images falls exponentially as a function of
      contrast. Moreover, the probability that a point is traversed by an occluding
      border in natural images always rises with contrast until reaching one. This rise
      tends to be supralinear and addition of noise (at low intensities) increases the
      supralinearity, shifting the rising portion of the curve towards higher
      contrasts. These findings lend support to the Minimal Local-Asperity hypothesis,
      which proposes that one of the main roles of early retinal processing is to
      extract optimally edge, contrast, and luminance attributes from the visual world
      based on previous knowledge about natural images.

PMID- 10958917
TI  - Color-opponent receptive fields derived from independent component analysis of
      natural images.
AB  - Independent Component Analysis (ICA) of images of natural scenes has been shown
      to generate basis functions, or filters, which resemble spatial [Bell & Sejnowski
      (1997). Vision Research, 37, 3327-3338; van Hateren & van der Schaaf (1998).
      Proceedings of the Royal Society of London B, 265, 359-366] and spatiotemporal
      [van Hateren & Ruderman (1998) Proceedings of the Royal Society of London B, 265,
      2315-2320] receptive fields of simple cells of the striate cortex. ICA yields
      statistically independent components which provide for a redundancy-reduced
      representation of the data. Using one of several published algorithms [Lee
      (1998). Independent component analysis: theory and applications. Boston; Kluwer
      Academic], we applied linear ICA to color images of natural scenes. The resulting
      independent component filters (ICFs) separate into either luminance or color
      filters. The luminance filters are localized and oriented edge detectors as
      reported previously. The color filters resemble either blue-yellow or red-green
      double-opponent receptive fields with various orientations. An equal number of
      each type of filter (luminance, red-green, and blue-yellow) is obtained. Thus,
      ICA predicts that spatiochromatic information is coded in statistically
      independent luminance, blue-yellow, and red-green opponent pathways with a
      relatively equal representation and specific spatial profiles at the cortical
      level.

PMID- 10958918
TI  - Performance asymmetries in visual search demonstrate failure of independent
      processing models.
AB  - We report psychophysical data from orientation-popout experiments that are
      inconsistent with a rather general decision model. Stimuli consisted of 121 line
      segments arranged on an 11x11 grid. There were two tasks: in the 1-Singleton Task
      all lines except one had the same orientation, and observers had to report which
      quadrant contained the singleton. In the 3-Singleton Task three quadrants
      contained orientation singletons and observers had to identify the quadrant
      without singleton. These tasks can be viewed as asymmetric search tasks, in which
      either a singleton-quadrant has to be found among three homogeneous quadrants, or
      a homogeneous quadrant has to be found among three singleton-quadrants. Using
      tools from signal-detection theory we show that the large performance asymmetries
      between 1-Singleton and 3-Singleton Tasks are inconsistent with any model that
      makes two (very basic and common) assumptions: (1) independent processing of the
      four quadrants and (2) an ideal-observer decision. We conclude that at least one
      of the two assumptions is inadequate. As a plausible reason for the model failure
      we suggest a global competition between salient elements that reduces popout
      strength when more than one singleton is present.

PMID- 10958919
TI  - Somatic cell mutations: can they provide a link between aging and cancer?
AB  - Cancers increase during aging in mammals, and an accumulating body of evidence
      suggests that mutational events too do likewise. Mutational events are intimately
      involved in the malignant process. One current view is that mutator phenotypes
      are required in malignant cells for a sufficient number of critical target genes
      to be affected. These mutator phenotypes are believed to result from underlying
      deficiencies in genes necessary to maintain genomic stability. This review will
      provide a framework for a discussion of cancer and aging by detailing with a pair
      of wise approach studies that address the relations between aging, cancer, and
      mutations. Results from these studies will be used to suggest that a mutator
      phenotype develops in the cells of older individuals in the absence of an
      underlying genetic deficiency. Instead, it is proposed that a mixture of
      chromosomal aberrations, DNA damage, and chronic exposure to genotoxic forces,
      including oxidative stress, provide the basis for this age-accelerated mutator
      phenotype.

PMID- 10958920
TI  - Paradigms in aging research: a critical review and assessment.
AB  - This is the first in a series of articles in which we intend to critically review
      some of the currently used models in gerontology research and evaluate their
      contribution to advancing our understanding of the phenomenon of senescence. The
      major theories of aging are considered. We discuss what makes a model useful in
      general and for aging research in particular. We suggest criteria for the
      selection of paradigms for the study of aging. The criteria we suggest for
      identifying underlying mechanisms that lead to age related changes are:
      intraspecies universality, intrinsicality, progressiveness, and interspecies
      universality. The subsequent articles of this series shall consider the merits
      and possible drawbacks of some of the most commonly used models of the biology of
      aging: (a) the yeast Saccharomyces cerevisiae; (b) the nematode, Caenorhabditis
      elegans and the fruitfly, Drosophila melanogaster; (c) mammalian cells in culture
      and telomerase model; (d) mitochondria and aging; (e) progeroid syndromes; (f) in
      vivo studies with laboratory rodent strains; and (g) plant senescence.

PMID- 10958921
TI  - Immune response to influenza vaccine in healthy elderly: lack of association with
      plasma beta-carotene, retinol, alpha-tocopherol, or zinc.
AB  - Immunity and nutritional status are compromised with age, yet the relationship
      between them is unclear. Immune responses and plasma micronutrient levels of 61
      healthy elderly (mean 81 years) and 27 young (mean 27 years) were assessed before
      and after immunization with trivalent influenza vaccine (FLU). FLU-induced
      proliferation and IFN-gamma levels of elderly were lower than young before and
      after immunization. Proliferation and IFN-gamma levels increased after
      immunization of young, but not elderly. FLU-induced IL-6 and IL-10 levels did not
      change after immunization of either group. While antibody titers to all three FLU
      components increased after vaccination of young and elderly, post-vaccination
      titers of elderly were lower than young. Although plasma retinol and zinc levels
      of young and elderly were similar before and after vaccination, elderly had
      higher plasma beta-carotene and alpha-tocopherol levels at both assessments that
      increased after vaccination. Importantly, plasma micronutrient levels were
      comparable for elderly with or without intact (titers >/=40 and fourfold rise
      post-vaccination) antibody responses after vaccination. These results suggest
      that differences in these plasma micronutrients (1) are not required to observe
      decreased FLU responses of healthy elderly compared to young and (2) are not
      associated with differences in antibody responses among healthy elderly.

PMID- 10958922
TI  - Cancer incidence in old age.
AB  - The incidence of all cancer increases with age through most of the human life
      span, but its real incidence at very old ages has not been well elucidated to
      date. Clarification of the real incidence of cancer in old age, especially among
      centenarians, may well provide pivotal information to understand the
      characteristics of humankind. In this study, autopsy records of the Annual of the
      Pathological Autopsy Cases in Japan, 1991-1996, vols. 34-39 (Japanese Society of
      Pathology, Tokyo) were used. Cases over 90 years old were studied individually
      for accurate analysis. The incidence of cancer peaked in the 6th decade and that
      of multiple cases in the 8th decade. In groups over 90 years of age, the
      incidence at 5-year intervals did not show any significant decrement. Moreover,
      the metastatic rate and rate of death due to cancer among centenarians was about
      three-fourths and two-thirds, respectively, of that of cases aged 90-94 years.
      The decrease in the metastatic ratio and less mortality due to cancer occurring
      at the oldest ages are considered due to the nature of cancer itself. The fact
      that the incidence of cancer does not increase would suggest that certain people
      among those of advanced age have a special resistance to it.

PMID- 10958923
TI  - Age-related changes of human bone marrow: a histometric estimation of
      proliferative cells, apoptotic cells, T cells, B cells and macrophages.
AB  - We performed an immunohistological study using biopsy samples of bone marrow
      obtained from patients, ranging in age from a newborn baby to 100 years old.
      Those patients suffering from hematological diseases or diseases that would be
      capable of affecting hematopoiesis were not included in the present study. The
      cellularity of the bone marrow did not change significantly with age during the
      first and the eighth decades, while the oldest group, ranging in age from 80 to
      100, revealed significantly low cellularity. Proliferative activity assessed by
      Ki-67-positive cells was high in the middle-aged group and declined slightly in
      the elderly group. It was of interest to note that the percentage of apoptosis
      was relatively low in the young and middle-aged group, but significantly
      increased in the elderly group. The percentage of T cells did not change greatly
      between the first and the fifth decades, peaked at the sixth decade and gradually
      decreased thereafter. The percentage of B cells was about 10% at the first
      decade, decreased thereafter until the third decade, then increased again showing
      a peak at the sixth decade, and decreased thereafter. The percentage of CD68
      positive cells was high in young patients, and decreased in the adult and elderly
      patients. The data in the present study suggest that hypocellularity in the bone
      marrow of elderly people could be ascribed partly to the increase of apoptosis,
      and might possibly be related to a decrease in the number of lymphocytes and
      macrophages, which would constitute part of the bone marrow microenvironment
      supporting hematopoiesis.

PMID- 10958924
TI  - Effects of ageing on proliferative ability, and the expressions of secreted
      protein, acidic and rich in cysteine (SPARC) and osteoprotegerin
      (osteoclastogenesis inhibitory factor) in cultures of human periodontal ligament
      cells.
AB  - Secreted protein, acidic and rich in cysteine (SPARC) has been suggested to play
      an important role in wound repair and mineralization.
      Osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) is a secreted
      protein that inhibits the maturation, activity and survival of osteoclasts. An
      examination of the changes in expression of these proteins as well as their
      proliferative ability according to ageing in cultured cells may elucidate
      characteristic changes in periodontal tissues induced by ageing. In the present
      study, proliferative ability and the expression of SPARC and OPG/OCIF were
      compared between cultures of human periodontal ligament (HPL) cells obtained from
      young and senior donors (in vivo cellular ageing) as well as in cultures of HPL
      cells at early and late passages (in vitro cellular ageing). Cumulative
      population doubling levels and cell population doubling time of HPL cells from
      young donors were greater and shorter, respectively, than those of HPL cells from
      senior donors. Levels of SPARC mRNA in HPL cells increased with cellular ageing
      in vivo. No change in the levels of OPG/OCIF mRNA in HPL cells with cellular
      ageing in vivo was observed. The changes in proliferative ability and the mRNA
      levels of SPARC and OPG/OCIF with cellular ageing in vitro were similar to those
      with ageing in vivo. This study demonstrated for the first time a relationship
      between in vivo and in vitro cellular ageing in the functional changes in HPL
      cells. These findings suggest that the impairment of periodontal ligament repair
      with ageing is due to the decrease in proliferative ability in HPL cells with
      ageing. Furthermore, the increase in SPARC with ageing may be related to changes
      in metabolism of periodontal ligament that occur with ageing.

PMID- 10958926
TI  - On the nature of aging.
AB  - Most of the aging theories are monistic in nature, they omit numerous key factors
      of senescence during the process of model creation. There are two main categories
      of these theories: program theories and error (mutation) ones. Program theories
      imply the existence of internal or external programs that determine the aging
      process ab ovo. The error theories involve explicit or implicit the idea that
      aging would not happen without the destructive factors that cause errors,
      mutations, regulation disorders, and in turn these processes finally lead to
      disfunctions and senescence. The aim of this paper is to indicate that aging may
      be multifactorial and the process of senescence may be determined by the
      information level of the organization. This level itself changes during
      senescence (including the information level of the genom that also alters by time
      because of, e.g. its 'fluid' character). According to this approach the aging
      process is determined by the sum effects of internal (e.g. genom) and external
      (material, energy, information) factors, although there are some elements that
      bear more importance than others. Subsequently, the maximal life-span is probably
      determined by the principle of the weakest element of the chain. Because of the
      high complexity of the human body where different information systems superpose
      each other, the cooperation of the elements (counter-effects, regulation) have
      the same determining importance as the information level of the unit parts
      (cells) have. The further aim of this paper is to show that the roots of certain
      diseases (e.g. cancer) could firmly be linked to the aging process itself. This
      interpretation offers two ways of influencing the process of senescence. It could
      be influenced by maintaining the information level of the organism via
      optimization or by changing (elevating) this level. All the factors that help to
      prevent the decrease of the information level of the organism could act against
      aging and certain diseases, and vice versa: the factors which deteriorate the
      state of the information system could contribute to the acceleration of the aging
      process.

PMID- 10958925
TI  - Different age-related effects of thymectomy in myasthenia gravis: role of
      thymoma, zinc, thymulin, IL-2 and IL-6.
AB  - Different age-related immune pathogenetic mechanisms in myasthenia gravis (MG)
      have been suggested because of restoration after thymectomy (Tx) of altered zinc,
      thymulin (TH) and T-cell subsets exclusively in early-onset patients (younger <50
      years), not in late-onset patients (older >50 years). In this context interleukin
      2 (IL-2), interleukin-6 (IL-6) and thymoma are crucial because both involved in
      MG pathogenesis and correlated with acetylcholine receptors (AchRs) Ab
      production. Moreover, IL-2 and IL-6 are zinc-dependent, are altered in aging and
      related with zinc and TH age-dependent declines. Moreover, zinc is relevant for
      immune efficiency. In order to confirm these different age-related pathogenetic
      mechanisms further, the role of thymoma, zinc, TH, IL-2 and IL-6 is studied in MG
      patients with generalized MG with and without thymoma before and 1 month and 1
      year after Tx. The high IL-2, IL-6, zinc, and AChR Ab levels observed before Tx
      are significantly correlated each other in younger MG patients (<50 years)
      independently by thymoma and in older MG patients (>50 years) with thymoma. No
      correlations exist in older MG patients without thymoma. Thymulin is not
      correlated with other parameters considered to be both in younger and older MG
      patients independently by the thymoma. Thymectomy restores zinc; immune
      parameters and AChR Ab are exclusively in the younger group, not in the older
      one. These findings suggest that IL-2 and IL-6, via zinc, rather than TH, may be
      involved in different age-related pathogenetic mechanisms mainly in early-onset
      MG. By contrast, thymoma may be involved in MG etiology in late-onset
      representing, as such, a useful discriminant tool for MG etiology between early
      and late-onset MG patients. Because autoimmune phenomena may rise in aging, a
      parallelism with altered immune functions during aging is discussed.

PMID- 10958927
TI  - Concentrations of insulin-like growth factor (IGF)-I, -II, and IGF binding
      protein-4, and -5 in human bone cell conditioned medium do not change with age.
AB  - We examined the effects of age on the secretion of insulin-like growth factor
      (IGF)-I, -II, and IGF binding protein-4, and -5 in long-term bone cell cultures
      from 71 female donors, aged 28-79 years. Our results suggest that under basal
      conditions, the intrinsic capacity of human bone cells to produce these IGF
      components is largely preserved with age.

PMID- 10958928
TI  - Biophysical and molecular properties of annexin-formed channels.
AB  - The annexins are water soluble proteins possessing a hydrophilic surface, which
      belong to a family of proteins which (a) bind ('annex') both calcium and
      phospholipids, and (b) form voltage-dependent calcium channels within planar
      lipid bilayers. Annexins types are diverse (94 annexins in 45 species) and they
      belong to an enormous multigene family that ranges throughout all eukaryotic
      kingdoms. Although the structure of these proteins is now well known their
      functional and physiological roles remain largely unknown and circumstantial.
      Various experimental approaches provided evidence that annexins function as
      Ca(2+) channels that could act as regulators of membrane fusion. The identity of
      annexins is derived from the conserved 34 kDa C-terminal domain which comprises
      four repeats - except for annexin VI, with eight repeats - of a sequence of
      approximately seventy amino acids, which holds the area known as the 'endonexin
      fold', with its identifying GXGTDE. Annexins have been placed into three
      subgroups of (1) tetrad core and short amino terminal, (2) tetrad core and long
      amino terminal, and (3) octad core and short amino terminal. The repeats are
      highly conserved, each forming a compact alpha-helical domain comprising five
      alpha-helices wound in a right-handed superhelix. Four domains are formed,
      arranged in a nearly flat and cyclical array, with domains I and IV, and II and
      III respectively forming two tightly organised modules with almost twofold
      symmetry. A hydrophilic pore lies at the centre of the molecule, forming a
      prominent ion channel coated with charged and highly conserved residues. The
      annexin molecule is slightly curved, with both a convex and a concave face. The
      cation/anion permeability ratios and the selectivity sequence of the ion channels
      formed by several annexins confirm the selectivity of the annexins for Ca(2+)
      over other divalent cations, and reveals the importance of structural sites, e.g.
      amino acid positions 17, 78, 95 and 112 for the identification of the ion
      channel's position, function and regulation. Some are sensitive to low doses of
      the phenothiazine drugs, trifluoperazine (an anti-schizophrenia drug) and
      promethazine (anti nausea drug) La(3+) and Cd(2+), (blockers of voltage-gated
      Ca(2+) channels) nifedipine (an inhibitor of non-activating Ca(2+) channels).
      There are two main competing models used to explain in vitro ion channel activity
      of annexins: one involves changes in the conductance of ion via electrostatic
      disturbance of the membrane surface; the other involves a much more extensive
      alteration in protein structure and a correspondingly deeper penetration into the
      membrane.

PMID- 10958929
TI  - Modulation and genetic identification of the M channel.
AB  - Potassium channels constitute a superfamily of the most diversified ion channels,
      acting in delicate and accurate ways to control or modify many physiological and
      pathological functions including membrane excitability, transmitter release, cell
      proliferation and cell degeneration. The M-type channel is a unique ligand
      regulated and voltage-gated K(+) channel showing distinct physiological and
      pharmacological characteristics. This review will cover some important progress
      in the study of M channel modulation, particularly focusing on membrane
      transduction mechanisms. The K(+) channel genes corresponding to the M channel
      have been identified and will be reviewed in detail. It has been a long journey
      since the discovery of M current in 1980 to our present understanding of the
      mysterious mechanisms for M channel modulation; a journey which exemplifies
      tremendous achievements in ion channel research and exciting discoveries of
      elaborate modulatory systems linked to these channels. While substantial evidence
      has accumulated, challenging questions remain to be answered.

PMID- 10958930
TI  - A decade of progress in understanding the structural basis of protein synthesis.
AB  - The key reaction of protein synthesis, peptidyl transfer, is catalysed in all
      living organisms by the ribosome - an advanced and highly efficient molecular
      machine. During the last decade extensive X-ray crystallographic and NMR studies
      of the three-dimensional structure of ribosomal proteins, ribosomal RNA
      components and their complexes with ribosomal proteins, and of several
      translation factors in different functional states have taken us to a new level
      of understanding of the mechanism of function of the protein synthesis machinery.
      Among the new remarkable features revealed by structural studies, is the mimicry
      of the tRNA molecule by elongation factor G, ribosomal recycling factor and the
      eukaryotic release factor 1. Several other translation factors, for which three
      dimensional structures are not yet known, are also expected to show some form of
      tRNA mimicry. The efforts of several crystallographic and biochemical groups have
      resulted in the determination by X-ray crystallography of the structures of the
      30S and 50S subunits at moderate resolution, and of the structure of the 70S
      subunit both by X-ray crystallography and cryo-electron microscopy (EM). In
      addition, low resolution cryo-EM models of the ribosome with different
      translation factors and tRNA have been obtained. The new ribosomal models allowed
      for the first time a clear identification of the functional centres of the
      ribosome and of the binding sites for tRNA and ribosomal proteins with known
      three-dimensional structure. The new structural data have opened a way for the
      design of new experiments aimed at deeper understanding at an atomic level of the
      dynamics of the system.

PMID- 10958931
TI  - Human skeletal muscle fibres: molecular and functional diversity.
AB  - Contractile and energetic properties of human skeletal muscle have been studied
      for many years in vivo in the body. It has been, however, difficult to identify
      the specific role of muscle fibres in modulating muscle performance. Recently it
      has become possible to dissect short segments of single human muscle fibres from
      biopsy samples and make them work in nearly physiologic conditions in vitro. At
      the same time, the development of molecular biology has provided a wealth of
      information on muscle proteins and their genes and new techniques have allowed
      analysis of the protein isoform composition of the same fibre segments used for
      functional studies. In this way the histological identification of three main
      human muscle fibre types (I, IIA and IIX, previously called IIB) has been
      followed by a precise description of molecular composition and functional and
      biochemical properties. It has become apparent that the expression of different
      protein isoforms and therefore the existence of distinct muscle fibre phenotypes
      is one of the main determinants of the muscle performance in vivo. The present
      review will first describe the mechanisms through which molecular diversity is
      generated and how fibre types can be identified on the basis of structural and
      functional characteristics. Then the molecular and functional diversity will be
      examined with regard to (1) the myofibrillar apparatus; (2) the sarcolemma and
      the sarcoplasmic reticulum; and (3) the metabolic systems devoted to producing
      ATP. The last section of the review will discuss the advantage that fibre
      diversity can offer in optimizing muscle contractile performance.

PMID- 10958932
TI  - Structure, function, and evolution of phosphoglycerate mutases: comparison with
      fructose-2,6-bisphosphatase, acid phosphatase, and alkaline phosphatase.

PMID- 10958933
TI  - Molecular cytogenetic analysis of uterine leiomyoma and leiomyosarcoma by
      comparative genomic hybridization.
AB  - Uterine leiomyomata are among the most common of human neoplasms and are
      associated with abnormal uterine bleeding, infertility, and abdominal pain.
      Uterine leiomyosarcomata are presumed to be the malignant counterpart to uterine
      leiomyomata and are very rare. Transformation of uterine leiomyoma (ULM) into
      uterine leiomyosarcoma (ULMS) is yet to be conclusively confirmed, and each type
      of tumor may represent a distinct genetic entity. We used comparative genomic
      hybridization (CGH) to evaluate DNA sequence copy-number changes in 12 specimens
      of ULM and 8 of ULMS. CGH analysis of ULM demonstrated chromosomal imbalances in
      8 of 12 (66. 7%) specimens. The most frequent ULM gains were observed at 9q34 (a
      novel finding) and on chromosome 19. Other ULM imbalances included gains and
      losses of chromosome 1p, losses on 7q, and gains on 12q. All ULMS specimens
      demonstrated chromosomal aberrations. Chromosome 1 imbalances were very
      prominent. The most frequent losses were detected on 14q and 22q. Losses on 14q
      are rarely seen in other types of leiomyo-sarcoma and may be a distinctive
      feature of ULMS. Gains on chromosomes 8, 17, and X were observed in half the
      cases and were accompanied by high-level amplification. Other chromosome arms
      overrepresented included 12q and 19p. The absence of specific anomalies common to
      all ULM and ULMS argues against their being benign-malignant counterparts.

PMID- 10958934
TI  - A comprehensive karyotypic analysis on a newly developed hepatocellular carcinoma
      cell line, HKCI-1, by spectral karyotyping and comparative genomic hybridization.
AB  - A continuously growing human hepatocellular carcinoma (HCC) cell line was
      established from a Chinese male, carrier of the hepatitis B virus (HBV). This
      cell line, designated HKCI-1, grows as an adhering monolayer of polygonal
      epithelial cells that embody one or more nuclei. HKCI-1 secretes alpha
      fetoprotein but shows no evidence of HBV carriage. Conventional banding analysis
      of the short-term cultured primary tumor and the propagated HKCI-1 revealed a
      chromosome modal number of near-triploidy. It was, however, impossible to derive
      their complete karyotype due to the complex nature of chromosomal rearrangements
      and many marker chromosomes of uncertain origin. Spectral karyotyping (SKY) is a
      newly developed molecular cytogenetic technique that allows the unprecedented
      discernment of chromosomal abnormalities. Spectral karyotyping analysis on HKCI-1
      and the primary tumor elucidated all aberrant chromosomes and revealed complex
      karyograms. Recurring aberrations detected in both primary tumor and HKCI-1
      included der(X)t(X;11)(q10;p10), der(1)t(1;10)(q10;?pq), der(4)t(4;16)(p10;q10),
      i(5p), del(5)(q13), der(7)t(7;21)(q32q10::q10), der(8)t(8;17)(q10;p10), and
      der(9)t(9;22)(q34;?pq). Comparative genomic hybridization (CGH) was employed to
      monitor the culture evolution in vitro. Genomic imbalances in HKCI-1 involved
      chromosomal losses on 4q, 5q13-qter, 8p, 9pter-q33, 10q, 11q, 13q, 16q, 17q12
      qter, and 22, and low-level gains on 6pter-q22, 7p, 8q, 9q34, 10p, 11p, 12,
      17pter-q11.2, 18, 19, 20, 21, and Y. High-level amplifications were also detected
      on 5pter-q12, 7q11.2-qter, and Xq. The corresponding CGH finding on the primary
      tumor indicated similar imbalances. TP53 mutational analysis showed that both
      HKCI-1 and the primary tumor had the aflatoxin-associated mutation in codon 249
      and an additional TP53 polymorphism in codon 72. Our present study demonstrates
      the value of combined SKY and CGH study in defining complex rearrangements and
      identifying cryptic translocations, and provides a comprehensive analysis on the
      chromosomal abnormalities in HKCI-1.

PMID- 10958935
TI  - Cytogenetic characterization of two colon cell lines by using conventional G
      banding, comparative genomic hybridization, and whole chromosome painting.
AB  - The heterogeneous nature of genetic alterations in cancer cells handicaps the
      full characterization of its occurrence and the analysis of their molecular bases
      and relation to biological processes. Although many cancer cells are highly
      aneuploid, in other cases, as in a subset of colorectal carcinomas displaying
      microsatellite instability, chromosomal aberrations are scarce. The aim of this
      study was to fully characterize both qualitatively and quantitatively, the
      karyotypes of two established colon carcinoma cell lines (LoVo and HCT 116)
      previously reported as being near diploid. An array of complementary cytogenetic
      techniques were used: G-banding, comparative genome hybridization (CGH), and
      whole-chromosome painting (WCP). Combinations of these techniques provided an
      accurate karyotype for the two cell lines: LoVo cells showed
      49,XY,t(2;12)(q13;p11.2),+5,+7,+12,i(15)(q10) and HCT 116 cells showed 45,X,
      Y,dup(10)(q24q26),der(16)t(8;16)(q13;p13), der(18)t(17;18)(q21;p11.3).
      Heterogeneity was also observed in both cell lines as shown by G-banding.
      Chromosomal unbalances determined by CGH (many of them related to structural
      reorganizations) were characterized by WCP, allowing the reliable identification
      of those chromosome markers that could not be completely identified by G-banding.
      We show that combined analysis with classical and molecular cytogenetic
      techniques provides an accurate map of chromosomal aberrations in these two cell
      lines not identified in previous investigations.

PMID- 10958936
TI  - Nonrandom rearrangements of 6p in malignant hematological disorders.
AB  - It is very uncommon to observe nontranslocation abnormalities (NTAs) involving
      the short arm of chromosome 6 (6p) in malignant hematological disorders (MHDs).
      By using conventional cytogenetics and fluorescence in situ hybridization (FISH)
      with chromosome-microdissection probes specific for 6p21 and 6p25, we observed
      five patients with myeloid malignancies and two patients with lymphoid
      malignancies to have 6p NTAs. On the basis of our data and those in the
      literature, it is possible to divide 6p NTAs into the following three groups in
      MHD: The first group presents with 6p NTAs as a sole or primary change in myeloid
      malignancies. There are only two cases reported in this group, including one case
      with del(6)(p23) and the present case with ins(6)(q23p23p25) identified by FISH
      only. The second group presents with 6p deletions as a sole or primary change in
      lymphoid malignancies. Three cases have been reported in this group, including
      one case with del(6)(p21p23), one with del(6)(p21), and the present case 2 with
      del(6)(p21). The third group has 6p deletions in addition to other known primary
      changes, present in both myeloid and lymphoid disorders, with 36 cases reported,
      including five cases from our series. Deletions involving 6p21, 6p22, or 6p23
      have been observed in both myeloid and lymphoid disorders. The present data
      provide cogent information for further molecular characterization of 6p anomalies
      in MHD.

PMID- 10958937
TI  - Comparative genomic hybridization in inherited and sporadic ovarian tumors in
      Israel.
AB  - To gain an understanding of the molecular mechanisms of ovarian cancer, we
      analyzed 16 ovarian tumors from Jewish Israeli patients by comparative genomic
      hybridization: 12 invasive epithelial tumors (including three BRCA1 and one BRCA2
      mutation carriers), 2 primary peritoneal carcinomatosis, 1 pseudomyxoma
      peritoneii tumor, and 1 sertoli cell tumor. We similarly analyzed 1 normal ovary
      from a BRCA1 mutation carrier, and 3 metastases. The most common abnormalities in
      epithelial tumors were amplification of 8q22.1-ter (8/12, 66.6%), 1q22-32.1
      (5/12, 41.6%), 3q, 10p (4/12, 33.3% for each), and deletions of 9q (5/12, 41.6%)
      and 16q21-24 (4/12, 33.3%). All 3 BRCA1 mutation carriers and 2 of 8 sporadic
      cases displayed 9q deletion, and 2 of 3 BRCA1 mutation carriers, but none of the
      sporadic cases, had deletion of chromosome 19. The range of genetic changes in
      primary peritoneal tumors and epithelial ovarian cancers was similar, though the
      mean number of alterations in the former was less (3.5/tumor versus 8/tumor). Our
      preliminary results may indicate that inherited predisposition to ovarian cancer
      possibly entails preferential somatic deletions of chromosomes 9 and 19.

PMID- 10958938
TI  - Structural and numerical aberrations of chromosome 22 in a case of follicular
      variant of papillary thyroid carcinoma revealed by conventional and molecular
      cytogenetics.
AB  - This study reports a case of papillary carcinoma with vesicular components
      showing multiclonal aberrations of chromosome 22 as revealed by RHG-banding
      cytogenetics and by fluorescence in situ hybridization (FISH; whole chromosome 22
      and BCR-ABL-specific locus probes, multi-FISH). Four clones with chromosome 22
      changes as the sole abnormality were seen. The main abnormal clone lacked the
      whole chromosome 22. A del(22)(q11) was observed in a second group of cells. The
      third clone had an idic(22). Finally, FISH revealed a fourth abnormal cell
      population with a der(17)t(?17;22). Some of these chromosome 22 alterations have
      been described in other solid tumors such as meningiomas and neurinomas,
      suggesting a common genetic pathway of tumor progression occurring in a multistep
      process. Chromosome 22 changes do not seem to be involved in pure papillary
      thyroid tumors and therefore could be related to the maintenance of a follicular
      type histological pattern.

PMID- 10958939
TI  - Detection of aberrations of 17p and p53 gene in gastrointestinal cancers by dual
      (two-color) fluorescence in situ hybridization and GeneChip p53 assay.
AB  - We performed dual (two-color) fluorescence in situ hybridization (FISH) using
      direct fluorescent labeling probes for p53 and chromosome 17 in six
      gastrointestinal (3 stomach and 3 colon) cancers. In three of these (1 stomach
      and 2 colon) the interphase cell nuclei showed an imbalance of signals for the
      p53 and chromosome 17; that is, the p53 signal count was lower than the
      chromosome 17 signal count, indicating deletion of the p53 gene. Moreover,
      metaphase FISH analysis demonstrated that those nuclei actually had a chromosome
      17 with deletion of the p53 gene. Interestingly, these three cases had an
      abnormal chromosome 17 copy number, that is, chromosome 17 aneusomy. Furthermore,
      to investigate the possibility of p53 mutation in tumors with an imbalance of
      signals for chromosome 17 and p53 per nucleus, we performed a GeneChip p53 assay
      which has recently been developed. GeneChip p53 assay demonstrated that a primary
      tumor sample from one colon cancer case had a heterozygous point mutation of CGT
      (Arg) to CAT (His) at codon 273 in exon 8. In addition, a sample of metastatic
      tumor in the liver from the same case revealed two heterozygous point mutations.
      One of them was the same mutation as that is the primary tumor; the other was GTG
      (Val) to GGG (Gly) at codon 217 in exon 6. In conclusion, we found that the
      combination of dual-color FISH and GeneChip p53 assay offered reliable results
      and important information concerning not only deletion of the p53 gene and
      chromosome 17 aneusomy but also p53 mutations. Using these techniques, we
      demonstrated that an imbalance of signals for chromosome 17 and p53 per nucleus,
      chromosome 17 aneusomy, and accumulation of p53 mutations had occurred during
      carcinogenesis and development of gastrointestinal cancers.

PMID- 10958940
TI  - Detection of integrated murine leukemia viruses in a mouse model of acute myeloid
      leukemia by fluorescence in situ hybridization combined with tyramide signal
      amplification.
AB  - This study was undertaken to develop a reliable method to enumerate and map
      somatically acquired, clonal, murine leukemia virus (MuLV) proviral insertions in
      acute myeloid leukemia (AML) cells from the BXH-2 mouse strain. This was achieved
      by using fluorescence in situ hybridization combined with tyramide signal
      amplification (FISH-TSA) and an 8.8 kilobase pair (kb) full-length ecotropic MuLV
      or 2.0 kb MuLV envelope (env) gene probe. Two-color FISH was utilized combining
      chromosome-specific probes for regions near the telomere and/or centromere and
      the MuLV probes. The technique reliably detected germline and somatically
      acquired, tumor-specific, MuLV proviruses in BXH-2 AML cell lines. It was
      possible to readily verify homozygous insertions at endogenous ecotropic MuLV
      loci, Emv1 (chromosome 5), Emv2 (chromosome 8) and a BXH-2 strain-specific locus
      (chromosome 11). This strategy also verified the presence of molecularly cloned
      proviral insertions within the mouse Nf1 gene and another locus on distal
      chromosome 11, as well as on chromosome 7 and chromosome 9 in BXH-2 AML cell line
      B117. The technique was also used to detect several new tumor-specific, proviral
      insertions in BXH-2 AML cell lines.

PMID- 10958941
TI  - A unique structural abnormality of chromosome 16 resulting in a CBF beta-MYH11
      fusion transcript in a patient with acute myeloid leukemia, FAB M4.
AB  - A 43-year-old female with a peripheral white cell count of 118.0 x 10(9)/L and
      96% blasts was diagnosed with acute myeloid leukemia (AML), FAB M4. Cytogenetics,
      performed on a bone marrow sample, revealed the following abnormal karyotype:
      46,XX,ins(16)(q22p13.1p13. 3). Fluorescence in situ hybridization (FISH)
      confirmed the inter-arm insertion using a probe for 16p. The result of this
      structural rearrangement was the fusion of CBF beta to MYH11 seen commonly in
      inv(16)(p13q22). The patient commenced high-dose intensive combination
      chemotherapy (big ICE; Idarubicin, Cytarabine, and Etopiside). Five days post
      chemotherapy, she developed febrile neutropenia. Despite broad spectrum
      intravenous antibiotics and antifungal therapy, the patient died at day nine post
      chemotherapy. This case demonstrates a previously unreported structural
      abnormality of chromosome 16 in a patient with AML M4, which represents a third
      mechanism to inv(16)(p13q22) and t(16;16)(p13q22) in producing the CBF beta-MYH11
      fusion. CBF beta-MYH11 fusions masked by cryptic translocations at the
      cytogenetic level have been detected by FISH and PCR techniques. Due to the
      improved prognosis associated with CBF beta-MYH11 fusions compared to the
      standard risk group for AML, its detection remains important.

PMID- 10958942
TI  - Characterization of the topoisomerase I locus in human colorectal cancer.
AB  - DNA topoisomerase I (topo I) is the principle target for Camptothecin and its
      analogues. The topo I gene is located on chromosome 20q11.2-q13.1 and variation
      in topo I gene copy number has been shown to have impact on the in vitro
      sensitivity to topoisomerase I inhibitor chemotherapy. Fluorescence in situ
      hybridization (FISH) was used to detect and compare the TOPO I gene copy number
      between metaphase and interphase nuclei in a panel of 7 colorectal cancer cell
      lines. TOPO I gene copy number varied from 2 to 8 between cell lines, and signal
      in interphase nuclei demonstrated a linear relationship with that detected in
      metaphase nuclei. The structure of gene amplification included isochromosome
      formation, amplicon extension, and marker chromosome generation. Comparative
      genomic hybridization (CGH) was then used to further define the region of gain on
      chromosome 20. The region of gain contained the topo I gene and involved nearly
      all of 20q in most cases. This demonstrates a high degree of intrinsic variation
      in topo I gene copy number and the involvement of a 20q amplicon in colorectal
      cancer, which may have important implications for colorectal tumorigenesis and
      the use of chemotherapy.

PMID- 10958943
TI  - Cytogenetic analysis of invasive breast cancer: a study of 27 Asian patients.
AB  - Tumor cytogenetic analysis from 27 patients with breast cancer diagnosed at the
      Singapore General Hospital revealed complex karyotypic aberrations in 12 cases.
      The study group comprised 25 women and 2 men, ranging in age from 33 to 78 years
      (median 52 years). Ethnic distribution consisted of 22 Chinese, 3 Malaysian, and
      2 Indian patients. Pathologic assessment disclosed 24 invasive ductal, 2 invasive
      mucinous, and 1 mixed invasive mucinous and ductal carcinomas. Histologic grading
      showed 3 grade 1, 10 grade 2, and 12 grade 3 tumors; 2 cancers were not graded,
      because they had been subjected to prior chemotherapy. Tumor sizes ranged from
      1.5 to 10 cm (median 3 cm). Eleven cases were axillary node negative, whereas the
      remaining 16 node-positive cancers affected as many as 3 nodes in 8 cases and 4
      or more nodes in another 8. Twenty cases demonstrated estrogen-receptor
      positivity, and 8 cases progesterone-receptor positivity. The spectrum of
      cytogenetic abnormalities involved chromosomes 1, 3, 6, 7, 8, 11, 16, and 17 and
      ranged from gains and deletions of both long and short arms, trisomy, monosomy,
      and other rearrangements. There was a trend toward the presence of karyotypic
      abnormalities in tumors of higher grade.

PMID- 10958944
TI  - Gains and losses of DNA sequences in childhood brain tumors analyzed by
      comparative genomic hybridization.
AB  - Primary central nervous system neoplasms are the most common solid tumors in
      children. Genetic changes underlying childhood brain-tumor development and
      progression are incompletely characterized. To get an overview of the genetic
      events leading to the development of brain tumors and to identify chromosomal
      regions that may contain genes important in brain-tumor progression, we employed
      a comparative genomic hybridization technique. Twenty-four pediatric primary
      brain tumors were analyzed in this study. DNA copy number changes were observed
      in most of the samples (79%), and almost all chromosomes were involved. The total
      number of genetic aberrations (copy-number gains and losses per tumor) was
      significantly higher in the cerebellar primitive neuroectodermal tumor subgroup
      than in the gliomas. The high-grade tumors had more DNA changes than did the low
      grade tumors. The most often gained chromosomes were: 6q (45%), 4q (34.5%), and
      chromosome 1 (24% of the cases). The minimal common regions involved in DNA gains
      were narrowed down to 6q14-16 and 4q26-28. Losses of a specific chromosome
      (partly or as a whole) occurred on average in 7% of the cases. Chromosomal
      regions that were most often lost included chromosome 1 (17%), chromosome 16
      (17%), and chromosome 2 (14%). These findings suggest that genes localized to
      these minimal common chromosomal regions play a role in the tumorogenesis of
      childhood brain tumors. Our results indicate: (1) a great degree of genomic
      imbalance in these tumors; (2) that a high number of aberrations correlate with
      aggressive tumor biology; (3) and that nonrandom genetic changes may be
      associated with particular tumor types.

PMID- 10958945
TI  - H-RAS, K-RAS, and N-RAS gene activation in human bladder cancers.
AB  - Bladder cancer is one of the leading causes of cancer death in most developed
      countries. In this work, 19 bladder cancer specimens, along with their
      infiltrations of the urinary bladder wall from the same patients, were examined
      for the presence of H-RAS, K-RAS, and N-RAS activation using a polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The H-RAS
      activation was found in 15 (about 84%) of the 19 bladder cancers studied. The
      same results were obtained in the infiltrating urinary bladder wall samples. N
      RAS gene mutations were observed in all cases (except 1) in which H-RAS gene
      mutations were detected. The results suggest a strong relationship between H-RAS
      and N-RAS gene activation in bladder cancer. Changes in the K-RAS gene in bladder
      cancers seem to be a rare event; this is in agreement with findings of other
      authors. We found activation of the gene in one specimen of bladder cancer and
      its infiltration of the urinary bladder wall in the same patient.

PMID- 10958946
TI  - Nonclonal chromosomal aberrations induced by anti-tumoral regimens in childhood
      cancer: relationship with cancer-related genes and fragile sites.
AB  - Cytogenetic studies were performed on 80 pediatric cancer patients to observe the
      chromosomal damage, both quantitative and qualitative, induced by chemotherapy.
      Peripheral blood lymphocytes (PBL) (n = 127) were obtained at diagnosis, during
      treatment, at remission, and at relapse, and chromosome analysis performed
      utilizing G-banding standard procedures. The results show a significant increase
      in the number of altered karyotypes (P = 0.03) in the samples during treatment,
      returning to values that were similar to those at diagnosis at 2-year remission.
      Most of the chromosomal aberrations (CA) detected during the chemotherapy
      regimens were nonclonal, unbalanced (75%), and involved chromosomes 1, 3, 5, 6,
      11, 12, 16, and 17 most frequently. There was also a marked increase of CA in
      samples at relapse with very similar features (type and distribution) to those
      detected during treatment. There was a good correlation between the chromosomal
      breakpoints in our series and fragile sites (58%), oncogene (75%), and tumor
      suppressor gene (33%) loci described in the literature. The results obtained
      suggest that cytostatic drugs induce a transient increase in chromosome fragility
      occurring at several cancer-associated breakpoints.

PMID- 10958947
TI  - Deletion 7p in gastric MALT lymphoma.
AB  - Deletion of the long arm of chromosome 7 has been related to loss of tumor
      suppressor genes which may constitute a primary step of carcinogenesis in many
      kinds of malignancies, including low-grade B-cell lymphoma. However, deletion of
      the short arm of chromosome 7, del(7p), in low-grade B-cell lymphoma has not been
      reported. Here, we report a case of gastric MALT lymphoma with the chromosome
      aberration del(7p) which progressed in spite of eradication of Helicobactor
      pylori. Deletion 7p may represent a new karyotypic change that is possibly
      related to autonomous growth of MALT lymphoma.

PMID- 10958948
TI  - Molecular characterization of der(15)t(11;15) as a secondary cytogenetic
      abnormality in acute promyelocytic leukemia with cryptic PML-RAR alpha fusion on
      17q.
AB  - A case of acute promyelocytic leukemia (APL) with cryptic PML-RAR alpha fusion on
      17q and add(15p) as a secondary abnormality was characterized using molecular
      cytogenetic techniques. Spectral karyotyping (SKY) showed that chromosome 11
      material was added to 15p, forming a der(15)t(11;15), which was refined to
      der(15)t(11;15)(q13.2;p13) with information obtained by comparative genomic
      hybridization (CGH). Interstitial insertion of chromosome 15 material into
      chromosome 17q was found by fluorescence in situ hybridization (FISH) with whole
      chromosome painting (WCP) probes. This study illustrates the necessity of a
      combination of molecular cytogenetics to decipher complex karyotypic
      abnormalities and cryptic translocations in leukemia.

PMID- 10958949
TI  - Lack of activating c-SRC mutations at codon 531 in rectal cancer.
AB  - Cellular SRC (c-SRC), which is the human homolog of the Rous sarcoma viral
      oncogene, v-src, is highly activated in colorectal cancer. Recently, a subset of
      colon cancers have shown a nonsense mutation at codon 531, which truncates c-SRC
      directly C-terminal to the c-SRC kinase regulatory domain. This specific mutation
      has been demonstrated to be activating, transforming, and tumorigenic and to
      promote metastasis. We investigated 100 rectal cancers, half of which had tumor
      spread outside the rectum, for this mutation by using direct sequencing. None of
      these tumors displayed any genetic alteration at this locus, and we thus conclude
      that the codon 531 mutation is a rare cause of c-SRC activation in rectal cancer.

PMID- 10958950
TI  - A case of near-triploidy in chronic myelogenous leukemia.
AB  - A 61-year-old woman with chronic myelogenous leukemia (CML) in accelerated phase
      had a near-triploid bone-marrow karyotype. This karyotype is an unusual finding
      in CML, as we review 12 previously published similar cases. These patients do not
      differ clinically from other patients with CML in blast crisis. The cytogenetic
      features of near-diploid and near-triploid CML are similar, except that relative
      loss of chromosomes is more common and that isochromosome 17q has not been
      reported in near-triploid CML.

PMID- 10958951
TI  - The Semaphore crab, Heloecius cordiformis: bio-indication potential for heavy
      metals in estuarine systems.
AB  - Although alterations at the organism level in decapod crustaceans on exposure to
      heavy metals have been evidenced in the laboratory, little examination of metal
      effects on morphology and population parameters have been explored in a field
      based situation. Relationships between morphological parameters, population
      demography and heavy metal sediment loadings were examined in conjunction with
      the accumulation of metals in the Semaphore crab, Heloecius cordiformis, in the
      Port Jackson and Hawkesbury River estuaries, Sydney, Australia. H. cordiformis
      exhibited sexual dimorphism, with males having larger carapace width, carapace
      length, chelae length and total mass than females. Sexes were subsequently
      treated separately to assess morphological differences among locations. Locations
      that had greater proportions of females with purple chelae and less females in
      the population tended to have higher sediment metal levels. These relationships
      were maintained over time, and could be employed as population-level biological
      indicators of heavy metal stress. Copper and zinc were regulated in the
      hepatopancreas of H. cordiformis. Lead was accumulated in the hepatopancreas of
      H. cordiformis in proportion to sediment lead levels, suggesting the species is
      both an appropriate candidate for bio-indication of lead pollution, and Pb is the
      main metal linked with population level differences. Accumulation of lead varied
      between sexes, indicating that sexes must be monitored separately. Smaller males
      accumulated more lead than larger males, suggesting size is an important
      consideration for lead accumulation.

PMID- 10958952
TI  - Seasonal variation of MXR and stress proteins in the common mussel, Mytilus
      galloprovincialis.
AB  - The accumulation of heat-shock HSP70 and MXR proteins in the digestive gland and
      gills respectively of the mussel (Mytilus galloprovincialis) has been examined in
      individuals collected monthly during 1 year from the mariculture areas located in
      the Ebro Delta (NW Spain). Both proteins were visualised and semi-quantified by
      western blot using commercially available monoclonal antibodies and subsequent
      image analysis. Two HSP-related bands of Mr 72 and 78 kDa and two MXR proteins of
      Mr 230 and 130 kDa were detected and their seasonal variations in expression
      levels recorded. A significant correlation between HSP70 and MXR expression was
      obtained, the maximum protein accumulation being detected during the summer
      period. These two parameters were also significantly correlated to water
      temperature at sample sites. These results suggest either a direct role of
      temperature in protein expression or an indirect role driven by food availability
      and growth.

PMID- 10958953
TI  - Glutathione-dependent biotransformation of 1-chloro-2,4-dinitrobenzene in
      arterial and venous blood of the striped bass (Morone saxitilis).
AB  - Glutathione (GSH) mediated metabolism of a model electrophile, 1-chloro-2,4
      dintrobenzene (CDNB), by striped bass (Morone saxitilis) whole blood and
      reconstituted erythrocytes equilibrated to 'arterial' and 'venous' blood gas
      concentrations was assessed. Reduced GSH was found to be an abundant nucleophile
      (2-2.4 mM) in striped bass erythrocytes. Incubation of whole blood and intact
      erythrocytes, reconstituted in phosphate buffer solution (PBS), with CDNB
      resulted in rapid depletion of >98% of cellular GSH levels and rapid, though not
      stoichiometric, accumulation of a glutathione S-conjugate, 2,4-dintrophenyl S
      glutathione (DNP-SG) within the 60 min exposure period. The GSH depletion half
      lives were 11.0+/-2.6 min and 10.3+/-2.0 min, respectively, for 'arterial' and
      'venous' trials using whole blood compared to 6.4+/-1.8 min and 7.1+/-0.9 min,
      respectively, for erythrocytes in PBS. The conjugate was not metabolized further
      within erythrocytes, but was slowly transported linearly from the cells to the
      plasma or PBS medium. Reconstitution of erythrocytes in PBS produced
      significantly greater rates of CDNB biotransformation compared to whole blood,
      although the total amount of DNP-SG formed per unit of GSH depleted was
      significantly lower. Differences may be attributed to altered rates of CDNB
      membrane permeation and/or efflux and changes in the rate of GSH oxidation in the
      presence of plasma versus PBS. Whole blood and erythrocytes in PBS equilibrated
      to 'arterial' and 'venous' blood gas concentrations showed no significant
      difference in rates of GSH depletion, DNP-SG formation, or conjugate efflux. GSH
      concentration decreased after exposure to CDNB and was not regenerated within the
      60 min incubation period. GSH reacted nonenzymatically with CDNB at a very slow
      and relatively insignificant rate under physiological blood gas concentrations.
      Enzymatic biotransformation of lipophilic electrophiles by erythrocytic GSH
      results in rapid depletion of the protective thiol and constitutes the first step
      in mercapturic acid formation. This investigation provides strong evidence for
      the presence of significant levels of glutathione S-transferase in striped bass
      erythrocytes.

PMID- 10958954
TI  - Observations on the interaction of zinc and cadmium uptake rates in crustaceans
      (amphipods and crabs) from coastal sites in UK and France differentially enriched
      with trace metals.
AB  - This paper presents results on the possible interaction of zinc and cadmium
      uptake rates in crustaceans. Zn and Cd uptake rates were measured in amphipods
      (Orchestia gammarellus) and crabs (Carcinus maenas and Pachygrapsus marmoratus)
      from five coastal sites in Britain and France subjected to different degrees of
      trace metal enrichment. The presence or absence of 100 ug l(-1) of one metal
      (1.53 uM l(-1) Zn, 0.89 uM l(-1) Cd) had an inconsistent effect on the rate of
      uptake of the other metal by O. gammarellus. The presence or absence of 50 ug l(
      1) of either zinc (0.76 uM l(-1)) or cadmium (0.45 uM l(-1)) had no effect on the
      rate of uptake of the other metal by C. maenas (from Millport, Scotland). Zinc
      and cadmium uptake rates were correlated in individual amphipods and crabs of
      both species from the five sites. These correlations indicate that zinc and
      cadmium might share common routes of uptake from solution by crustaceans, but the
      metals do not consistently interact competitively or synergistically at the
      exposure concentrations investigated. Regression coefficients of the relationship
      between zinc and cadmium uptake rates in amphipods and crabs showed occasional,
      but inconsistent, differences between sites and over time. All three crustaceans
      take up zinc from solution at a higher rate than cadmium for the same total
      dissolved metal molar concentration, but at a lower rate than cadmium per free
      metal ion molar concentration.

PMID- 10958955
TI  - High ammonia tolerance in fishes of the family Batrachoididae (Toadfish and
      Midshipmen).
AB  - Three fish species of the family Batrachoididae, the gulf toadfish (Opsanus
      beta), the oyster toadfish (Opsanus tau), and the plainfin midshipman (Porichthys
      notatus) demonstrated exceptionally high tolerances to elevated water ammonia
      with 96-h LC50 values of 9.75, 19.72 and 6 mM total ammonia, respectively. Using
      pH values we calculated the corresponding unionized ammonia (NH(3)) values to be
      519, 691 and 101 uM, respectively. These values are well above typical values for
      most teleost fishes, but close to those of ureotelic fish examined to date.
      Following sublethal high ammonia exposure (HAE) blood and tissue (brain, liver
      and muscle) sampling confirmed that internal ammonia levels rose substantially in
      all three species, suggesting that they were not simply avoiding toxicity by
      impermeance to ammonia. The three species of batrachoidids can be characterized
      in the following manner with respect to the inabilities to synthesize and excrete
      urea, based on these studies and prior research: O. beta (fully ureotelic)>O. tau
      (moderately ureotelic)>P. notatus (ammoniotelic). While some of the high ammonia
      tolerance for O. beta and O. tau can be explained by their ability to detoxify it
      to urea, other mechanisms must be at play for P. notatus. Further experiments
      determined that all three species possess rather high activities of glutamine
      synthetase (GSase) in brain especially (60-180 U g(-1)), that glutamine
      accumulates in many tissues, and that LC50 values are correlated positively with
      brain GSase activity. Taken together, our results suggest that
      alternative/additional mechanisms for ammonia detoxification via urea synthesis
      must be considered to explain the exceptionally high ammonia tolerance of this
      group.

PMID- 10958956
TI  - Relationships between acid-soluble thiol peptides and accumulated Pb in the green
      alga Stichococcus bacillaris.
AB  - Stichococcus bacillaris, an ubiquitous green microalga accumulated inorganic lead
      (Pb) from aqueous solutions extra- and intracellularly. In response to Pb uptake
      acid-soluble thiol peptides (glutathione - GSH and phytochelatins - PC) were
      synthesized. The proportion of the intracellular Pb uptake by algal cells was low
      and comprised only 3-6% of the total metal sorption. The intracellular uptake was
      dependent on external Pb concentration, time of metal exposure and cell
      metabolism. Pb accumulation in alga was determined by means of 210Pb radiometry.
      Reduced GSH and PC were determined in algal cells using HPLC with the post-column
      derivatization with Ellman's reagent. Within the studied concentration range 0.1
      20 uM, inorganic lead caused a significant production of induced thiol peptides:
      PC (n=2-4) and some other unidentified oligopeptides, probably (GluCys)n. The
      time of appearance and the concentration of individual oligomers of
      phytochelatins were dependent on the external Pb concentration and time of metal
      exposure. In algal cells exposed to Pb, significant changes in the GSH level
      accompanying the formation of the induced thiol peptides were also observed. The
      GSH level decreased in the cells exposed to the lower (up to 10 uM) studied Pb
      concentrations or increased in the cells treated with higher (20 uM) Pb
      concentrations. The thiol groups originated from induced peptides (mainly
      phytochelatins) followed a stoichiometric relationship 2:1 to the intracellular
      Pb amounts, however, only at the lowest studied external concentration (0.1 uM).
      At higher concentrations (up to 2.5 uM), intracellular Pb concentration was equal
      or even exceeded (at Pb>2.5 uM) two to three times the level of induced thiols.
      S. bacillaris accumulated intracellularly by 46% more Pb in light than in dark
      and the level of induced thiol peptides was significantly higher in the cells
      exposed to Pb under illumination. The rapid formation of these peptides in S.
      bacillaris in response to Pb, and their elimination (by about 90%) when algae
      were placed into the Pb-free solution reveal a tight regulation of GSH and
      phytochelatin pools in the algal cells exposed to toxic metals. The obtained
      results suggest that both PCs and GSH are the primary line of defence against the
      Pb toxicity. Additionally, the induced thiol peptides in S. bacillaris could be a
      good indicator of intracellular Pb availability and stress at the metal
      concentrations found in polluted fresh waters.

PMID- 10958957
TI  - Effects of chronic sublethal exposure to waterborne Cu, Cd or Zn in rainbow
      trout. 1: Iono-regulatory disturbance and metabolic costs.
AB  - The relationships among growth, feeding behaviour, ion regulation, swimming
      performance and oxygen consumption in rainbow trout (Oncorhynchus mykiss) were
      compared during chronic exposure (up to 100 days) to sublethal levels of
      waterborne Cd (3 ug.l(-1)), Cu (75 ug.l(-1)) or Zn (250 ug.l(-1)) in moderately
      hard water (hardness of 140 mg.l(-1), pH 8). A pattern of disturbance, recovery
      and stabilization was evident for all three metal exposures, although the degree
      of disturbance, specific response and time course of events varied. Growth was
      unaffected by any of the metals under a regime of satiation feeding but appetite
      was increased and decreased in Cu- and Cd-exposed trout respectively. Critical
      swimming speed was significantly lowered in fish chronically exposed to Cu, an
      effect associated with elevated O(2) consumption rate at higher swimming speeds.
      Branchial Na(+)/K(+) ATPase activity was elevated in Cu-exposed fish but not in
      Cd-exposed trout. Disruption of carcass Na(+) and Ca(2+) balance was evident
      within 2 days of exposure to either Cd, Cu or Zn, with subsequent recovery to
      control levels. The loss of Ca(2+) in trout exposed to waterborne Cd persisted
      longest, and recovery took approximately a month. The physiological response of
      trout to chronic Cu exposure involves mechanisms that result in an associated
      metabolic cost. In comparison, Cd is neither a loading nor a limiting stress and
      acclimation to chronic Cd-exposure does not appear to involve a long term
      metabolic cost.

PMID- 10958958
TI  - Effects of chronic sublethal exposure to waterborne Cu, Cd or Zn in rainbow trout
      2: tissue specific metal accumulation.
AB  - Tissue specific metal accumulations (gills, liver, kidney and whole body) in
      rainbow trout (Oncorhynchus mykiss) were compared during chronic exposure (up to
      100 days) to sublethal levels of waterborne Cd (3 ug.l(-1)), Cu (75 ug.l(-1)) or
      Zn (250 ug.l(-1)) in moderately hard water (hardness of 140 mg.l(-1), pH 8.0). A
      general pattern of tissue metal increase and stabilization was evident for all
      three metals, although the degree and time course of accumulation varied. The
      exception to this general pattern was a lack of Zn accumulation in the liver and
      kidney although small amounts did accumulate in the gills and whole body.
      Accumulation of Cu occurred primarily in the liver while for Cd the kidney was
      the major organ of accumulation. Exponential modeling was employed to compare and
      contrast the saturation concentration and time to half saturation of various
      tissues. Accumulation of essential metals (Cu and Zn), if it occurred, was rapid
      and increases were relatively low. For example the time to half saturation during
      Cu exposures was always less than 2 weeks and the maximum level of accumulation
      was less than four times background levels. For non-essential Cd, time to half
      saturation for the liver and kidney was always longer than 5 weeks and modeled
      saturation concentrations were up to 80-fold higher than background. The response
      to Cu and Zn suggested an active regulation of tissue burdens while that of Cd
      appears to be more passive, resulting in continuous metal accumulation over an
      extended time course. While the initial patterns of accumulation for each metal
      were generally consistent with the damage, repair and acclimation pattern from
      concurrent physiological measurements it was clear that tissue metal accumulation
      was not a good indicator of either exposure of physiological impact.

PMID- 10958959
TI  - Calcium control of zinc uptake in rainbow trout.
AB  - Water hardness is known to control the uptake and toxicity of zinc and other
      metals through either chemical competition, biological acclimation, or both
      processes. The dominant process controlling zinc uptake has not been previously
      elucidated, nor has the effect of calcium been investigated independently of
      other cations. We determined zinc uptake by rainbow trout acclimated and exposed
      to four calcium treatments: (1) low calcium (6.5 mg Ca/l; 160 uM) acclimation and
      low calcium exposure (LL); (2) low acclimation and high calcium (131 mg Ca/l;
      3300 uM) exposure (LH); (3) high acclimation and low exposure (HL); and (4) high
      acclimation and high exposure (HH). Trout were exposed to sublethal zinc (100 ug
      65Zn/l; 1.5 uM) for 24 h, and whole body and gill 65Zn levels were determined.
      Zinc uptake was approximately linear during the 24 h exposure period and uptake
      was calcium dependent. 65Zn uptake by trout was 22 ug/kg per h in the LL
      treatment and 4.5 ug/kg per h in the HH treatment. 65Zn uptake by trout in the LH
      and HL treatments was 13 and 10 ug/kg per h, respectively. 65Zn uptake in gills
      was also significantly reduced by calcium acclimation or exposure. Trout in the
      LH and HH treatments had five fold lower 65Zn concentrations than LL treatment
      fish. The results of this study demonstrate that calcium reduces zinc uptake
      through both biological acclimation and chemical processes, and that the
      protective effects of calcium are approximately additive.

PMID- 10958960
TI  - The effect of creosote on the growth of an axenic culture of Myriophyllum
      spicatum L.
AB  - Due to the importance of submersed, rooted macrophytes to the aquatic ecosystem
      and the use of creosote impregnated structures adjacent to or within water
      bodies, a study was conducted using an axenic culture of Myriophyllum spicatum to
      determine the effect of creosote on this aquatic macrophyte. Four plants were
      cloned and exposed to nominal creosote concentrations ranging from 0.16 to 200
      mg/l for 14 days. A variety of response parameters were assessed, including shoot
      and root length, number of roots and nodes, and dry weight biomass, as well as
      visual observations on plant colouring and morphology. Regression and ANOVA
      analyses were conducted to determine EC50s and significant differences. Biphasic
      responses were observed for shoot length, node production and biomass, with shoot
      length showing statistically significant stimulation (hormesis) at creosote
      concentrations below 13.3 mg/l. EC50 values of 55.1 (CI 40-60) mg/l, 33.4 (CI 26
      48) mg/l and 86 (CI 70-120) mg/l were determined for shoot length, dry weight and
      node production, respectively. Root number was significantly higher at 3.6 mg/l
      and root length was significantly reduced at 4.5 mg/l creosote, within the
      concentration range that stimulated shoot growth. Visual changes, including an
      increase in pink colouration and changes in the location of root initiation, were
      also observed in the same creosote concentration range that affected root length
      and numbers. Therefore, it appears that changes in root growth and location of
      root initiation may be the most sensitive endpoints for creosote effects on
      Myriophyllum.

PMID- 10958961
TI  - The effect of creosote on membrane ion leakage in Myriophyllum spicatum L.
AB  - Creosote is a complex chemical mixture used as a wood preservative that has the
      potential to contaminate aquatic systems via spills or leaching from treated wood
      structures. Aquatic macrophytes are important components of aquatic systems,
      which may be adversely affected by creosote contamination. Several chemicals that
      are constituents of creosote are known to affect cell membranes in various
      organisms. Therefore, the effect of creosote on the membrane permeability of the
      aquatic macrophyte Myriophyllum spicatum was investigated. Apical meristems from
      axenic Myriophyllum plants were exposed for 4 days to 8 creosote treatments
      (ranging from 0.1 to 92 mg creosote/l) plus controls. Following the exposure, the
      ion leakage from the cellular membranes was determined via conductivity
      measurements. The concentration of 15 polycyclic aromatic hydrocarbons (PAHs) in
      the growth medium and in the plant tissue was also determined. A significant
      increase in ion leakage was observed at all creosote concentrations, even those
      in which no biological effects were observed on plant growth. However, saturation
      of the growth medium with PAHs was observed, thus indicating that nominal
      creosote concentrations may over-estimate the actual exposure.

PMID- 10958962
TI  - A fast and simple turbidimetric method for the determination of sulfate in
      sulfate-reducing bacterial cultures.
AB  - A standard turbidimetric assay for the determination of sulfate in water was
      modified with the objective of achieving a quick and simple method for monitoring
      the decrease of sulfate in cultures of sulfate-reducing bacteria. The effects of
      sulfate concentration, mixing time and the ratio of sample to conditioning
      reagent were optimized using a central composite face-centered response surface
      model design. The results suggested that a mixing time of 30 s resulted in
      smaller absorbance variance, the variance in absorbance measurements tended to
      increase with concentration of sulfate and that the ratio between the amount of
      conditioning reagent and sample had no significant influence on the absorbance
      variance. The modified assay thus developed is simple and quick, and covers a
      comparatively large sulfate concentration range (0-5 mM) compared to the standard
      turbidimetric assay.

PMID- 10958963
TI  - Construction of promoter probe vectors for Synechocystis sp. PCC 6803 using the
      light-emitting reporter systems Gfp and LuxAB.
AB  - Two promoter probe vectors were constructed for the cyanobacterium Synechocystis
      sp. strain PCC 6803 using reporter genes, which can be easily detected and
      quantified in vivo by the ability of their encoded proteins to emit light. The
      vectors allow the transcriptional fusion of promoter sequences with the gfp and
      luxAB genes, respectively, and their stable integration into a neutral site of
      the Synechocystis chromosome. Functionality of these vectors was demonstrated by
      cloning the promoter of the isiAB operon into both promoter probe vectors and
      analyzing the stress-dependent emission of light by the obtained reporter
      strains. As was found before for the isiAB operon, the P(isiAB) reporter gene
      fusions were induced by iron starvation and high salt stress. Induction rates of
      mRNA of the wild type operon and the reporter gene fusions were found to be
      essentially the same, indicating that a promoter fragment containing all
      necessary regulatory elements has been cloned. However, using the gfp gene a slow
      increase of protein and fluorescence was found, while the luxAB reporter gene
      constructs led to a rapid increase in luminescence. The same was found after
      retransfer of cells back into control media, in which the Gfp protein disappeared
      slowly, while the LuxAB-based luminescence decreased rapidly. These experiments
      show that both reporter genes can be used in Synechocystis: the luxAB system
      seems to be favourable regarding reaction time, while the gfp system has the
      advantage of being independent from any substrate.

PMID- 10958965
TI  - Development of polymerase chain reaction-based assays for bacterial gene
      detection.
AB  - Polymerase chain reaction-based assays provide rapid, simple, and sensitive
      detection of bacterial genes, but are not without their drawbacks. This review
      summarizes the principal advantages and disadvantages of PCR-based bacterial gene
      detection, provides guidelines for the development and validation of new PCR
      assays, and describes potential pitfalls that may be encountered and how these
      can be avoided.

PMID- 10958964
TI  - Efficient amplification of multiple transposon-flanking sequences.
AB  - Transposon mutagenesis is a very useful tool for gene identification in bacteria.
      Once the transposon mutants of interest are isolated, it is often necessary to
      identify the sequences that flank the transposon insertions. We devised an
      efficient method for specific amplification of transposon-flanking sequences that
      requires the sequence information of only transposon-specific sequences. The
      basic steps for this method consists of (1) digestion with a restriction enzyme,
      (2) ligation with a Y-shaped linker and (3) polymerase chain reaction
      amplification using a transposon-specific primer and a primer specific to the Y
      shaped linker. The feasibility of this method was demonstrated with mini-Tn5
      mutants of Salmonella typhimurium. We also found that this method can be used for
      simultaneous amplification of multiple transposon-flanking sequences.

PMID- 10958966
TI  - Modified pyrogallol-initiated immunogold-silver enhancement technique applicable
      to prokaryotes.
AB  - A modified immunogold-silver enhancement technique that was designed to reduce
      the nonspecific granular background staining, particularly for application on
      prokaryotic organisms, is reported. Aerial oxidation of pyrogallol contained in
      the commercial silver enhancer solution was effectively controlled during storage
      and in the reaction mixture. A combination of strategies such as storing the
      reagent under argon, modifying it using 0.5% (w/v) anhydrous sodium sulfite,
      reducing the concentration of silver ions in the reaction mixture and limiting
      the length of the silver enhancement reaction considerably reduced the granular
      background staining. The modified technique was demonstrated on the bacterium
      Xanthomonas campestris pv. malvacearum (Smith) Dye. A 7-min silver enhancement
      step produced little background staining, while optimal silver intensification of
      the bacterium pre-treated with the immunogold label was achieved.

PMID- 10958967
TI  - Altered cell surface hydrophobicity of lipopolysaccharide-deficient mutant of
      Bradyrhizobium japonicum.
AB  - The authors previously isolated a lipopolysaccharide (LPS) deficient Tn5-mutant
      of Bradyrhizobium japonicum, and subsequently isolated the LPS gene region. In
      this study the LPS deficiency of B. japonicum was studied in terms of its cell
      surface characteristics. By monitoring the kinetics of the partition with
      hexadecane the LPS-mutant was found to be far more hydrophobic than the wild type
      strain; the partition coefficients were 3.19 min(-1) for the mutant, as compared
      with only 1.40 min(-1) for the wild type. When the mutant was transformed with
      the cloned LPS gene, the transformant regained the wild type phenotypes,
      including the cell surface hydrophobicity (CSH) and LPS profile. A polyacrylamide
      gel electrophoretic analysis of LPS demonstrated that the O-antigenic part of LPS
      was completely absent in the mutant. The LPS-mutant of B. japonicum was visually
      distinguishable from the wild type after a simple centrifugation of the cells.

PMID- 10958968
TI  - Electrospray ionization/mass spectrometry compatible reversed-phase separation of
      phospholipids: piperidine as a post column modifier for negative ion detection.
AB  - An electrospray ionization (ESI) compatible separation of phospholipids (PL),
      phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidylcholine
      (PC), was performed on a C18 column by reversed phase High Performance Liquid
      Chromatography (HPLC) with minimal ESI suppression. The mobile phase, used
      isocratically, consisted of methanol and water. ESI was used to efficiently
      transfer the ions present in solution to the gas phase for mass spectrometric
      (MS) detection. Formation of negative ions was reinforced by incorporating
      piperidine post column. Limits of detection (LOD) and limits of quantitation
      (LOQ) were experimentally determined to be 20 and 60 fmol/microl, respectively,
      when acquiring data in the selected ion monitoring (SIM) mode monitoring three
      ions with a single quadrupole MS. When acquiring data from m/z 110-900 in the
      scanning mode, the LOD and LOQ were experimentally determined to be 1 pmol/microl
      and 3 pmol/microl. When acquiring product ion spectra for m/z 747, the LOD and
      LOQ were experimentally determined to be 446 attomol/microl and 1.3 fmol/microl,
      respectively.

PMID- 10958970
TI  - Different methods for extracting bacteria from freshwater sediment and a simple
      method to measure bacterial production in sediment samples.
AB  - The efficiency of different treatments was tested to extract bacterial cells from
      freshwater sediment samples. The influence of sonication, density gradient
      centrifugation, fixation by formalin and centrifugation speed on bacterial
      recovery was investigated. The method developed by Smith and Azam [Mar. Microb.
      Food Webs 6 (1992) 107] to measure microbial activity on bacterioplankton (3H
      leucine incorporation), was also evaluated in sediment samples. After 1 min of
      sonication bacterial abundance was reduced by about 47% in diluted sediments with
      tetrasodium pyrophosphate. With the addition of Percoll after sonication,
      bacterial counts were not significantly different (P<0.05). Fixation by formalin
      increased bacterial counts using sonication. However, higher bacterial abundance
      was estimated in non-sonicated samples. Bacterial abundance in samples
      centrifuged at 7000xg with and without Percoll was not significantly different
      (P<0.05). Highest bacterial abundance was obtained after centrifugation at low
      speed (750xg). Bacterial abundance decreased with higher centrifugation speed
      (750, 1500 and 3000xg), the difference, however, was not significant. Bacterial
      production ranged from 0.10 microg C cm(-3) d(-1) in autoclaved sediment to 0. 27
      microg C cm(-3) d(-1) in untreated sediment. The radioactivity measured in
      controls of both untreated and autoclaved sediment was high (70 and 91%,
      respectively), indicating a high level of leucine adsorption in sediment
      particles. In contrast, radioactivity in control samples previously centrifuged
      was markedly lower (6%). Despite the high values of radioactivity in the
      controls, bacterial production in untreated sediment was significantly higher
      than in centrifuged sediment (P<0.05).

PMID- 10958969
TI  - Measuring soil microbial community diversity using polar lipid fatty acid and
      denaturing gradient gel electrophoresis data.
AB  - The possibility of calculating useful microbial community diversity indices from
      environmental polar lipid fatty acid and 16S rDNA PCR-DGGE data was investigated.
      First, the behavior of the species richness, Shannon's, and Simpson's diversity
      indices were determined on polar lipid fatty acid profiles of 115 pure cultures,
      communities constructed from those profiles with different numbers of species,
      and constructed communities with different distributions of species. Differences
      in the species richness of these artificial communities was detected by all three
      diversity indices, but they were insensitive to the evenness of the distribution
      of species. Second, data from a field experiment with substrate addition to soil
      was used to compare the methods developed for lipid- and DNA-based diversity
      indices. Very good agreement was found between indices calculated from
      environmental polar lipid fatty acid profiles and denaturing gradient gel
      electrophoresis profiles from matched samples (Pearson's correlation coefficient
      r=0.95-0.96). A method for data pre-treatment for diversity calculations is
      described.

PMID- 10958971
TI  - Use of PCR analysis for detecting low levels of bacteria and mold contamination
      in pharmaceutical samples.
AB  - PCR assays were developed and compared to standard methods for quality evaluation
      of pharmaceutical raw materials and finished products with low levels of
      microbial contamination. Samples were artificially contaminated with less than 10
      CFU of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and
      Aspergillus niger. Bacterial DNA was extracted from each enrichment broth by mild
      lysis in Tris-EDTA-Tween 20 buffer containing proteinase K while mold DNA was
      extracted by boiling samples in Tris-EDTA-SDS buffer for 1 h. A 10-microl aliquot
      of extracted DNA was added to Ready-To-Go PCR beads and specific primers for E.
      coli, S. aureus, and P. aeruginosa. However, 50-microl aliquots of extracted mold
      DNA were used for amplification of specific A. niger DNA sequences. Standard
      methods required 6-8 days while PCR detection of all microorganisms was completed
      within 27 h. Low levels of microbial contamination were detected in all raw
      materials and products using PCR assays. Rapid quality evaluation of
      pharmaceutical samples resulted in optimization of product manufacturing, quality
      control, and release of finished products.

PMID- 10958972
TI  - Application of a chromogenic medium and the PCR method for the rapid confirmation
      of L. monocytogenes in foodstuffs.
AB  - Detection of Listeria monocytogenes in foodstuffs by conventional cultivation
      methods carried out according to EN ISO guidelines is rather time-consuming.
      Therefore, two alternative methods were applied for rapid confirmation of L.
      monocytogenes in foodstuffs. Inoculum from liquid selective broth was plated on
      PALCAM and OXFORD agar and on chromogenic agar medium RAPID L. mono. Suspect
      colonies from PALCAM were confirmed according to EN ISO standards and by the
      multiplex PCR method. In total, 990 samples of foodstuffs were investigated and
      63 strains of L. monocytogenes were isolated. The chromogenic medium RAPID L.
      mono provided results comparable to PCR, it is easier to handle and provides
      considerable financial savings.

PMID- 10958973
TI  - Staurosporine-induced apoptosis in cultured chick embryonic neurons is reduced by
      polyethylenimine of low molecular weight used as a coating substrate.
AB  - The survival of neurons largely depends on adhesion to extracellular matrix
      proteins. This study investigated the influence of polycationic macromolecules of
      different molecular weights used as coating substrates on apoptosis in primary
      cultures of chick embryonic neurons. Coating of the culture flasks with
      positively charged polyethylenimine (PEI) of 12, 32 and 1616 kDa led to different
      susceptibilities of the neurons to apoptosis induced by staurosporine and serum
      deprivation. In cultures grown as usual on polylysine (PL)-coated flasks, we
      found, after 24 h of incubation in medium with serum (controls), serum-free
      medium and staurosporine (200 nM)-containing serum-free medium, 15, 35 and 63%
      apoptotic neurons, respectively as evaluated by nuclear staining with Hoechst
      33258. Using 12-kDa PEI as a coating substrate, only 11, 15 and 47% apoptotic
      neurons could be determined in controls, serum-deprived and staurosporine-treated
      cultures, respectively. No change in the percentage of apoptotic neurons was
      found after 24 h of serum deprivation or treatment with staurosporine in cultures
      grown on 32-kDa PEI compared with cultures grown on PL. However, in staurosporine
      treated cultures grown on 1616-kDa PEI, the percentage of apoptotic neurons was
      even higher than in cultures grown on PL. Immunostaining using neurofilament (NF)
      antibodies revealed that the reduction of staurosporine-induced apoptosis using
      12-kDa PEI instead of PL as a coating substrate was accompanied by a reduced
      disruption and aggregation of the neurofilaments. Thus, the usage of the newly
      synthesized 12-kDa PEI as a coating substrate enhanced neuronal resistance to
      apoptosis.

PMID- 10958974
TI  - Carbachol and acetylcholine delay the early postdenervation depolarization of
      muscle fibres through M1-cholinergic receptors.
AB  - The resting membrane potential (RMP) of denervated muscle fibres of rat diaphragm
      muscle is depolarized by approximately 8-10 mV during the first 3 h after nerve
      section and this early postdenervation depolarization is reduced substantially by
      the presence of 5x10(-8) M acetylcholine (ACh) or carbachol (CB). The muscarinic
      antagonist atropine (Atr; 5x10(-9) to 5x10(-6) M) reduced the effect of CB in a
      dose-dependent manner (K(i)=7x10(-8) M) and increased the rate of the early
      postdenervation depolarization. In lower doses (5x10(-7) M), Atr acted only in
      the presence of an allosteric stabilizator hexamethylene-bis-[dimethyl-(3
      phtalimidopropyl)ammonium] (W-84). Also pirenzepine, a specific inhibitor of the
      M1 subtype of muscarinic receptor, blocked the action of CB in a dose-dependent
      manner with an apparent inhibition constant K(i)=1x10(-7) microM. DAMP, a
      specific M3 antagonist, was without effect on the muscle hyperpolarization
      induced by CB. CB also hyperpolarized the membrane potentials of muscles which
      were denervated for 1-3 days. It is concluded that ACh and CB protect the muscle
      fibres from early depolarization through M1-cholinergic receptors on the muscle
      membrane. These particular receptors can apparently mediate the 'trophic', non
      impulse regulation of RMP in skeletal muscles when they are activated by
      acetylcholine released non-quantally.

PMID- 10958975
TI  - VAMP-2 promotes neurite elongation and SNAP-25A increases neurite sprouting in
      PC12 cells.
AB  - Recent studies suggest that the soluble N-ethylmaleimide-sensitive factor
      attached protein (SNAP) receptor (SNARE)-mediated membrane fusion system is
      involved in vesicle fusion in the plasma membrane that allows expansion for
      neurite elongation. There have been several reports analyzing the effects of
      neurite outgrowth by inhibition of SNAREs. In this study, we took the opposite
      approach by overexpressing green fluorescent protein (GFP)-fusion SNAREs,
      including VAMP-2, SNAP-25A, and syntaxin1A, in PC12 cells to investigate the role
      of SNAREs in the neurite outgrowth of PC12 cells. Neurite outgrowth analysis
      demonstrated that: (1) GFP-VAMP-2 increased the length of individual neurites,
      without changing the number of neurites per cell; (2) GFP-SNAP-25A increased the
      number of neurites per cell, with no change in the length of the individual
      neurites. In both cases, the total length of neurites per cell was increased; (3)
      GFP-syntaxin1A resulted in no significant change, either in neurite length, or in
      the number of neurites per cell. These findings suggest that when overexpressed
      in PC12 cells, VAMP-2 can promote neurite elongation, while SNAP-25A can
      stimulate neurite sprouting. On the other hand, overexpression of syntaxin1A
      neither promotes nor inhibits neurite outgrowth. Thus VAMP-2 and SNAP-25A play
      different roles in neurite elongation and sprouting.

PMID- 10958976
TI  - Contribution of TTX-resistant C-fibres and Adelta-fibres to nociceptive flexor
      reflex and non-flexor-reflex pathways in cats.
AB  - The contribution of Adelta-fibres and C-fibres activated by noxious heat
      stimulation of the central pad of the foot to nociceptive spinal flexor reflex
      pathways (FRA-type) and to nociceptive excitatory reflex pathways to foot
      extensors (non-FRA type) was investigated in high spinal cats. A-fibres were
      completely blocked by tetrodotoxin (TTX), leaving C-fibre conduction intact.
      Thus, effects persisting after TTX were attributed to nociceptive C-fibres while
      the contribution of nociceptive Adelta-fibres was defined by the difference
      between those effects and the control effects before TTX. The initial action of
      noxious stimulation on both types of reflex action was mediated predominantly by
      Adelta-fibres, while the later action was mainly mediated by C-fibres. In two
      (out of seven) experiments Adelta-fibres exerted a significant inhibitory
      influence on the C-fibre action in FRA pathways, but such an inhibitory
      interaction between the two fibre groups was absent in the non-FRA reflex
      pathways. The technique of TTX application at the peripheral nerve proved to be a
      reliable method for a long-lasting selective investigation of C-fibre effects.
      The results revealed that both Adelta- and C-fibres contributed to nociceptive
      FRA and non-FRA reflex pathways.

PMID- 10958978
TI  - B2 exon splicing of nonmuscle myosin heavy chain IIB is differently regulated in
      developing and adult rat brain.
AB  - Two isoforms of nonmuscle myosin heavy chain IIB (MHC-IIB) are generated by
      alternative splicing; MHC-IIB(B2) differs from MHC-IIB(DeltaB2) by the insertion
      of B2 exon cassette near the actin binding region. Here we examined expressions
      of the two splice variants in developing and adult rat brains by in situ
      hybridization with isoform-specific oligonucleotide probes. In adult, MHC
      IIB(DeltaB2) mRNA was highly expressed in neurons of the cerebral cortex,
      hippocampus, and cerebellum, whereas MHC-IIB(B2) mRNA was mainly distributed in
      the brainstem and cerebellum, with the highest level in Purkinje cells. During
      development, MHC-IIB(DeltaB2) mRNA was predominantly expressed in various regions
      of embryonic and neonatal brains, whereas MHC-IIB(B2) mRNA was low during
      embryonic stages. Up-regulation of MHC-IIB(B2) started in the cerebellum during
      early postnatal stages when dendritogenesis and synaptogenesis occur actively in
      Purkinje cells. We further employed immunofluorescence using two antibodies (one
      recognizing both splicing variants and another specific to MHC-IIB(B2)), and
      found similar and dense localization in cell bodies and dendrites of Purkinje
      cells. Therefore, splicing of the B2 exon cassette undergoes distinct temporal
      and spatial regulations in the brain in vivo, and the different exon usage seems
      unlikely to affect the somato-dendritic localization of MHC-IIB.

PMID- 10958977
TI  - Slow recovery of goldfish retinal ganglion cells' soma size during regeneration.
AB  - The goldfish optic nerve regenerates after sectioning. Recently both short-term
      (30 days) and long-term (4 months) recovery of various goldfish behaviors were
      observed after optic nerve section. Using intracellular injection of Lucifer
      Yellow (LY) the morphology of regenerating ganglion cells in goldfish retina
      after optic nerve section over a 4 month period have been investigated. In normal
      retinas, most cells (96-98%) were 7-10 microm in soma diameter which increased
      with increasing distance from the optic disc. Only two or three short, thin
      processes could be traced with LY. The remaining cells (2-4%) were 13-16 microm
      in soma diameter and all of the long dendritic trees could be traced with LY. The
      most conspicuous morphological change observed was cellular hypertrophy, which
      occurred for 20-90 days after axotomy. Neuronal processes were also hypertrophic
      in this period. The percentage increase in hypertrophy of the central ganglion
      cells tended to be slightly higher compared to cells from other regions. These
      morphological changes peaked at 60 days after axotomy and fully disappeared by
      120 days after axotomy. The slow recovery of ganglion cells' soma size may
      reflect the slow return to the normal number of optic axon terminals in the
      tectum during regeneration.

PMID- 10958979
TI  - 5-Hydroxytryptamine-induced outward currents mediated via 5-HT(1A) receptors in
      neurons of the rat dorsolateral septal nucleus.
AB  - Effects of 5-hydroxytryptamine (5-HT) on neurons of the rat dorsolateral septal
      nucleus (DLSN) were examined by intracellular and whole-cell patch-clamp
      recording techniques. An outward current was induced by 5-HT (1-100 microM) in a
      concentration-dependent manner. The EC(50) for 5-HT was 4.8 microM. Also, 8-OH
      DPAT (10-100 microM) produced the outward current an EC(50) of 17 microM.
      Amplitudes of the outward currents produced by 5-HT (100 microM) and 8-OH-DPAT
      (100 microM) were 117+/-4 (n=6) and 58+/-8 pA (n=6), respectively. Fluvoxamine
      (200 nM), a specific serotonin re-uptake inhibitor, enhanced the 5-HT (1 microM)
      induced outward current: the EC(50) for 5-HT was 0.5 microM in the presence of
      fluvoxamine (200 nM). L-694247 (100 microM) and CP 93129 (100 microM) also
      produced outward currents with amplitudes of 33+/-3 (n=4) and 18+/-5 pA (n=4),
      respectively in DLSN neurons. DOI (100 microM) and RS 67333 (100 microM) did not
      produce outward currents. NAN-190 shifted, in a parallel manner, the
      concentration-response relationship of 5-HT to the right. The Lineweaver-Burk
      plot of the concentration-response curve showed that NAN-190 depressed the 5-HT
      induced current in a competitive manner. The current-voltage relationship
      indicates that the 5-HT-induced current reversed polarity at a potential close to
      the equilibrium potential of K(+). Ba(2+) (100 microM-1 mM) partially depressed
      the outward current produced by 5-HT. These results suggest that 5-HT induces
      multiple K(+) currents via 5-HT(1A) receptors in DLSN neurons.

PMID- 10958980
TI  - Changes in the localization of NAP-22, a calmodulin binding membrane protein,
      during the development of neuronal polarity.
AB  - NAP-22, a neuronal tissue-enriched acidic membrane protein, is a Ca(2+)-dependent
      calmodulin binding protein and has similar biochemical characteristics to GAP-43
      (neuromodulin). Recent biochemical studies have demonstrated that NAP-22
      localizes in the membrane raft domain with a cholesterol-dependent manner. Since
      the raft domain is assumed to be important to establish and/or to maintain the
      cell polarity, we have investigated the changes in the localization of NAP-22
      during the development of the neuronal polarity in vitro and in vivo, using
      cultured hippocampal neurons and developing cerebellum neurons, respectively.
      Cultured hippocampal neurons initially extended several short processes, and at
      this stage NAP-22 was distributed more or less evenly among them. During the
      maturation of neuronal cells, NAP-22 was sorted preferentially into the axon.
      Throughout the developmental stages of hippocampal neurons, the localization
      change of NAP-22 was quite similar to that of tau, an axonal marker protein, but
      not to that of microtubule-associated protein-2 (MAP-2), a dendritic marker
      protein. Further confocal microscopic observation demonstrated the colocalization
      of NAP-22 and either tau or vesicle-associated protein-2 (VAMP-2). A comparison
      of the time course of the axonal localization of NAP-22 and GAP-43 showed that
      NAP-22 localization was much later than that of GAP-43. The correlation between
      the expression of NAP-22 and synaptogenesis in the cerebellar granular layer,
      particularly in the synaptic glomeruli, was also investigated. There existed many
      VAMP-2 positive synapses but no NAP-22 positive ones in 1-week-old cerebellum. On
      sections of 2-week-old cerebellum, accumulation of NAP-22 to the synaptic
      glomeruli was clearly observed and this accumulation became clearer during the
      maturation of the synaptic structure. The present results suggest the possibility
      that NAP-22 plays an important role in the maturation and/or the maintenance of
      synapses rather than in the process of the axonal outgrowth, by controlling
      cholesterol-dependent membrane dynamics.

PMID- 10958981
TI  - Construction of a stable and highly infectious intron-containing cDNA clone of
      plum pox potyvirus and its use to infect plants by particle bombardment.
AB  - An infectious plum pox potyvirus cDNA clone was constructed placing a copy of the
      full-length sequence of the virus genome between an enhanced cauliflower mosaic
      virus 35S promoter and a nopaline synthase termination signal. Stabilization of
      the clone and faster growth of bacteria, in addition to higher plasmid yield,
      followed a modification consisting of the insertion of an intron which
      interrupted the viral open reading frame at the P3 region. This intron-containing
      clone was infectious when inoculated into plants after undergoing in vivo
      transcription and splicing. Particle bombardment delivery of the cDNA greatly
      increased the efficiency of plant infection.

PMID- 10958982
TI  - Sequence analysis and deletion of porcine adenovirus serotype 5 E3 region.
AB  - A 3000 basepair (bp) region corresponding to the E3 region, the flanking pVIII
      and part of the fiber protein genes, of the two prototype strains (HNF-61 and HNF
      70) of porcine adenovirus serotype five (PAdV-5) was sequenced. A potential E3
      promoter and poly-A signals were identified. The size of the E3 region was 2039
      (strain HNF-61) and 2020 bp (strain HNF-70) the largest E3 so far reported among
      PAdVs. Three open reading frames (ORF2-4) were identified within the E3 region.
      Based on the predicted amino acid (aa) sequences ORF2 was similar to other
      adenovirus E3 ORFs, ORF3 showed some similarity to a bovine adenovirus (BAdV-1)
      ORF. ORF4 was unique to PAdV-5. E3 mRNA transcripts were detected early in
      infection by Northern blot analysis. Genomic clones of HNF-70 with a 1505 or 1237
      bp deletions in the E3 region were constructed to map non-essential regions.
      After transfection of the DNA into swine testicle cells, virions were recovered
      for only the shorter 1237 bp deletion. At least 60% of the E3 region was not
      essential for virus replication, bringing the theoretical vector capacity of a
      helper independent PAdV-5 to 2.9 kb.

PMID- 10958983
TI  - Differences between the coat protein amino acid sequences of English and Scottish
      serotypes of Raspberry ringspot virus exposed on the surface of virus particles.
AB  - The region of the RNA 2 coding for the putative helper/movement protein and the
      coat protein (CP) of each of six isolates of Raspberry ringspot virus was
      sequenced and these sequences were compared with the published sequence of the
      Scottish type isolate. Minimal differences were detected among the putative
      translations of the helper/movement proteins, however, multiple alignment and
      phylogenetic analysis of the putative CPs separated the English and Scottish
      serotypes into two distinct clades. Superimposing the amino acid sequences of the
      CPs of these two serotypes on the 3D model for the CP of a comovirus/nepovirus,
      showed that eight of the differences identified between the two serotypes
      occurred on the surface of the protein. Inspection of the recently reported
      structure of the capsid protein of Tobacco ringspot virus, the type member of the
      genus Nepovirus, indicated identical locations for these differences. The change
      of H (Scottish isolates) to R (English isolates) at position 219 in the amino
      acid sequences of the viruses occurred on an exposed, erect surface loop. The
      potential role of this change, and other unique differences between the amino
      acid sequences of the two serotypes, in the specificity of nematode transmission
      of the virus is discussed.

PMID- 10958984
TI  - Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of
      hand, foot and mouth disease during an epidemic in Taiwan, 1998.
AB  - A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan
      in 1998, in which more than 80 children died of shock syndrome with pulmonary
      edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In
      order to understand the virological basis responsible for mortality on this
      scale, nucleotide sequences of VP1 that is important for serotypic specificity,
      and the 5'-non-coding region (5'-NCR) that is important for replication
      efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'
      NCR of nine EV71 isolates derived from specimens of fatal patients and seven
      isolates derived from uncomplicated HFMD patients showed that all but one isolate
      fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD
      belonged to genotype C that was clustered along with one isolate from Taiwan in
      1986. Complete sequence analysis of two selected isolates, one from the spinal
      cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD,
      confirmed a high degree (97-100%) of identity in nucleotide sequence throughout
      the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide
      homology was 90-91%. The identity of the deduced amino acid sequence in the 3C
      region that encodes viral proteinase dropped further to 86%, a result of missense
      mutations at the first nucleotide position of many codons.

PMID- 10958985
TI  - Antibody-dependent enhancement of HSV-1 infection by anti-gK sera.
AB  - We previously reported that vaccination of BALB/c mice with the baculovirus
      expressed HSV-1 glycoprotein K (gK) or passive transfer of gK purified IgG to
      naive BALB/c mice causes severe exacerbation of HSV-1 induced corneal scarring
      following ocular challenge. In addition, a productive chronic infection, rather
      than a latent infection, is found in most trigeminal ganglia. These phenomena are
      accompanied by a very high T(H)1+T(H)2 response in the eye (Ghiasi, H., Cai, S.,
      Nesburn, A.B., Wechsler, S.L., 1996. Vaccination with herpes simplex virus type 1
      glycoprotein K impairs clearance of virus from the trigeminal ganglia resulting
      in chronic infection. Virology 224, 330-333; Ghiasi, H., Cai, S., Slanina, S.,
      Nesburn, A. B., Wechsler, S.L., 1997. Nonneutralizing antibody against the
      glycoprotein K of herpes simplex virus type-1 exacerbates herpes simplex virus
      type-1-induced corneal scarring in various virus-mouse strain combinations.
      Invest. Ophthalmol. Vis. Sci. 38, 1213-1221; Ghiasi, H., Hofman, F.M., Cai, S.,
      Perng, G.C., Nesburn, A.B., Wechsler, S.L., 1999. Vaccination with different HSV
      1 glycoproteins induces different patterns of ocular cytokine responses following
      HSV-1 challenge of vaccinated mice. Vaccine 17, 2576-2582). In the studies
      reported here, we investigated the hypothesis that anti-gK serum produces
      antibody-dependent enhancement (ADE) of ocular HSV-1 infection. We found that gK
      vaccinated mice had significantly higher HSV-1 titers in their eyes than gD or
      mock-vaccinated mice and that anti-gK sera enhanced HSV-1 infection in the
      macrophage cell line U937. In addition, passive transfer of anti-gK sera to naive
      mice 24 h prior to ocular HSV-1 challenge also increased viral replication. These
      results were consistent with ADE of HSV-1 by sera to gK. This suggests that the
      severely exacerbated corneal disease seen following HSV-1 ocular challenge of gK
      vaccinated mice is a result of ADE. The ability of gK sera to cause harmful ADE
      may impact HSV-1 vaccine development.

PMID- 10958986
TI  - Genetic diversity of RNA segments 5, 7 and 9 of the Palyam serogroup orbiviruses
      from Japan, Australia and Zimbabwe.
AB  - Reverse transcriptase-polymerase chain reaction (RT-PCR) methods, based on the
      sequences of RNA segments 5, 7 and 9 of Chuzan virus, were established for
      specific detection and molecular characterization of the Palyam serogroup
      orbiviruses. Nucleotide sequences obtained from the amplified cDNA fragments of
      these three genes of 24 isolates were analyzed and compared individually to
      determine the intra-serogroup phylogenetic relationship of Japanese, Australian
      and Zimbabwean isolates. It seems that Chuzan virus isolates in Japan are
      genetically stable. Interestingly, mutations have occurred almost simultaneously
      on these three genes of Chuzan virus. In all cases, isolates from the same
      geographical area were closely related to each other at the molecular level,
      irrespective of serotype. The data suggested that the Palyam serogroup viruses
      can be differentiated into geographically distinct groups and that the viruses
      evolve independently in the different gene pools. A strain KY-115 was considered
      to be produced by reassortment of genome segments between different groups.
      Restriction fragment length polymorphism (RFLP) analysis of these PCR products is
      useful for rapid discrimination of isolates and for detection of genetic
      mutations.

PMID- 10958987
TI  - Rubella virus nonstructural protein 2 is a minor immunogen.
AB  - The full-length nonstructural protein P90 of rubella virus (RV) was expressed as
      recombinant protein in Escherichia coli bacteria, as well as in Vero cells.
      Monoclonal antibodies raised against the protein specifically reacted with the
      protein in both P90-transfected and RV infected Vero cells. Ninety human sera
      obtained from reconvalescents, vaccinees and patients with acute RV infection
      were tested for reactivity against the P90 protein. A weak immune reaction was
      detected only in a small minority (8%), indicating that P90 is minor immunogen
      for RV and is not suitable for diagnostic purposes.

PMID- 10958988
TI  - Cell cycle G2 arrest induced by HIV-1 Vpr in fission yeast (Schizosaccharomyces
      pombe) is independent of cell death and early genes in the DNA damage checkpoint.
AB  - HIV-1 Vpr induces cell cycle G2 arrest, morphological changes and cell death in
      human and fission yeast cells. The cellular targets for G2 arrest were expected
      to be the inhibitory phosphorylation sites of Cdc2, as G2 arrest correlates with
      hyperphosphorylation and decreased activity of Cdc2 in both human and fission
      yeast cells. In this study, we present direct evidence of genetic suppression of
      Vpr-induced G2 arrest by cdc2 mutations. Mutations in cdc2 (cdc2-1w and cdc2-3w)
      reduce the ability of Vpr to induce G2 arrest. A strain with a mutation changing
      the Tyr15 of Cdc2 to the non-phosphorylated Phe (Y15F) eliminated Vpr-induced G2
      arrest indicating that Tyr15 of Cdc2 is the sole target for induction of G2
      arrest by Vpr. Although the G2 arrest induced by DNA damage also proceeds through
      phosphorylation of Tyr15, the rad1, rad3, rad9 and rad17 mutations, which
      eliminate the G2 checkpoint for DNA damage, did not block the G2 arrest induced
      by Vpr. Furthermore, Vpr expression did not alter sensitivity of these rad
      mutants to UV radiation. Thus, the pathways for the induction of G2 arrest by DNA
      damage and Vpr are not identical. Interestingly, Vpr still induces cell death and
      morphological changes in the Y15F Cdc2 strain indicating that G2 arrest is not
      required for morphological changes and cell death. This conclusion was further
      supported by the observation that mutations in Vpr, which have lost their ability
      to induce G2 arrest, retained the ability to kill cells.

PMID- 10958989
TI  - Bovine herpesvirus 1 glycoprotein G is required for viral growth by cell-to-cell
      infection.
AB  - The bovine herpesvirus 1 (BHV-1) US4 gene encodes glycoprotein G (gG), which is
      conserved in the majority of alphaherpesviruses. In order to identify the role of
      BHV-1 gG in the viral infection cycle, a gG minus BHV-1 mutant and its gG
      positive revertant were constructed and their growth characteristics in Madin
      Darby bovine kidney (MDBK) cells were compared. The gG minus mutant formed
      smaller plaques than the gG-positive BHV-1 in MDBK cells. When a monolayer
      culture of MDBK cells was infected with BHV-1 at a low multiplicity of infection
      and overlaid with semi-solid growth medium, under which adsorption of the mature
      virion released in the medium was inhibited, gG-positive BHV-1 multiplied, while
      the growth of the gG negative BHV-1 was severely inhibited. These data suggest
      that BHV-1 gG functions in direct cell-to-cell transmission mechanism of BHV-1 in
      tissue culture.

PMID- 10958990
TI  - Science in practice: can health care reform projects in central and eastern
      Europe be evaluated systematically?
AB  - Since the beginning of the 1990s, health care reform projects have taken place in
      many of the former Communist countries, but these projects are rarely evaluated
      systematically. Evaluation, however, is an important tool for increasing their
      rationality and continuity. The aim of this paper is to identify the difficulties
      in the efforts towards systematic evaluation and draw lessons for the future. For
      this aim, the requirements for a more rigorous, controlled evaluation are
      compared with our experiences of evaluating a health care reform project in the
      Slovak republic. From this comparison a number of discrepancies arise: it was
      difficult to set clear and realistic goals at the start of the project; the
      outcomes of the project could not always be measured, nor could 'the process'
      always be distinguished from the outcomes. Systematic evaluation was further
      hampered by an insufficient degree of structuration of the project, in advance
      and during the implementation, and by the absence of a tradition and
      infrastructure for data collection. On the basis of the experiences and relevant
      literature, recommendations for future evaluations are formulated. The main
      lesson is that, given the context, often it will not be possible to use an
      ambitious evaluation design, and concessions need to be made. At the same time,
      continuous efforts towards more systematic evaluation procedures should be made,
      but it is wise and more sustainable to do this in an incremental way.

PMID- 10958991
TI  - Creating a strategic management plan for magnetic resonance imaging (MRI)
      provision.
AB  - We were commissioned by the West Midlands NHS Regional Specialized Services Group
      (RSSG) to formulate a strategic plan for the management of Magnetic Resonance
      Imaging (MRI) within the West Midlands, UK. We needed to establish whether an
      increase in MRI provision was required, and if so to develop criteria to shape
      both the nature and location of MRI provision. We found that the UK had
      relatively low MRI provision per capita by international standards, and that the
      West Midlands region of the UK had less than the UK average level of MRI
      provision per capita. Within the region there was a 'mixed economy' of MRI
      provision involving fixed site scanners owned by the NHS and private companies,
      and private sector mobile MRI provision. There was little evidence of
      inappropriate MRI use, but considerable evidence of under-provision. Most MRI
      scanners in the region were heavily utilized, and average waiting times for MRI
      frequently exceeded guidelines (of a maximum 13-week wait for non-urgent MRI
      scans). Projections from NHS Trusts, MRI suppliers, and experts in the MRI field,
      led us to the conclusion that demand for MRI was likely to grow by between 12.5
      and 18.5% per annum. This implies that 8-14 additional MRI scanners might be
      required within the West Midlands over the next 5 years, to meet existing, and
      rising demand for MRI. We therefore developed criteria (outlined in the paper) to
      enhance the productive and allocative efficiency of the deployment of MRI
      provision, whilst improving the configuration of MRI with reference to
      geographical equality of access to MRI.

PMID- 10958993
TI  - Deductibles in health insurance: can the actuarially fair premium reduction
      exceed the deductible?
AB  - The actuarially fair premium reduction in case of a deductible relative to full
      insurance is affected by: (1) out-of-pocket payments, (2) moral hazard, (3)
      administrative costs, and, in case of a voluntary deductible, (4) adverse
      selection. Both the partial effects and the total effect of these factors are
      analyzed. Moral hazard and adverse selection appear to have a substantial effect
      on the expected health care costs above a deductible but a small effect on the
      expected out-of-pocket expenditure. A premium model indicates that for a broad
      range of deductible amounts the actuarially fair premium reduction exceeds the
      deductible.

PMID- 10958994
TI  - Determination of defensin HNP-1, HNP-2, and HNP-3 in human saliva by using LC/MS.
AB  - The mass spectral profiling of saliva by liquid chromatography mass spectrometry
      in relation to particular types of pain is being examined. The aim is to develop
      a profile that could be useful for the assessment of patients and their treatment
      programs, as well as identifying unknown compounds observed in saliva. Defensin
      human neutrophil peptide-1 (HNP-1) and defensin HNP-2 were identified and
      confirmed, whereas defensin HNP-3 was tentatively identified. Linear calibration
      range of defensin HNP-1 and HNP-2 was 0.25 to 3 microg/ml with R(2) values of >
      0.99 for both. The detection limit for defensin HNP-1 and HNP-2 was estimated at
      0.1 microg/ml. The healthy subjects surveyed in this study had readily measurable
      salivary concentrations of defensin HNP-1 (8.6 +/- SD 8.0 microg/ml) and defensin
      HNP-2 (5.6 +/- SD 5.2 microg/ml).

PMID- 10958995
TI  - Expression of functional recombinant scorpion beta-neurotoxin Css II in E. coli.
AB  - The gene for a beta-neurotoxin [Centruroides suffusus suffusus toxin II (Css II)]
      from the scorpion C. suffusus suffusus was synthesized by recursive PCR and
      cloned into the expression vector, pET15b. This recombinant vector was
      transformed into a thioredoxin mutant host bacterial cell, AD 494(DE3)pLysS, and
      expression was induced with isopropyl thiogalactoside (IPTG). Although the level
      of expression was low, the recombinant toxin was found only in the soluble
      fraction with no evidence for the formation of inclusion bodies as had been
      observed previously with other scorpion toxins. The recombinant Css II was
      purified by successive ion-exchange and hydrophobic interaction chromatography.
      Nuclear magnetic resonance (NMR) and circular dichroism (CD) spectral
      measurements indicate that the protein has a native structure with no indication
      of denatured species. The recombinant neurotoxin inhibits the uptake of
      [(3)H]GABA [gamma-aminobutyric acid (GABA)] in neuronal cells as effectively as
      natural beta-toxins.

PMID- 10958996
TI  - Solid-phase synthesis of a modified 13-residue seminalplasmin fragment on 1,6
      hexanediol diacrylate-crosslinked polystyrene support.
AB  - A novel 1,6-hexanediol diacrylate cross-linked resin was prepared that was
      subsequently functionalized by using chloromethyl methyl ether to afford a high
      capacity resin. The resin exhibited good swelling and its application in the
      successful synthesis of a 13-residue peptide corresponding to the fragment of
      seminalplasmin has been illustrated. The resin was chemically inert at peptide
      synthetic conditions.

PMID- 10958997
TI  - Responses of frog skin Na(+) and Cl(-) transport to guanylin.
AB  - A possible role for the peptide hormone guanylin was investigated in frog skin
      (Rana pipiens) epithelium. Sodium and chloride fluxes in response to this peptide
      were evaluated in Ussing-type chambers. Net and unidirectional Na(+) fluxes were
      measured by using (22)Na(+) and atomic absorption analysis of total [Na(+)],
      whereas net Cl(-) fluxes were measured by using electrometric titration for [Cl(
      )]. Mucosal application of guanylin (0.5-2.0 micromol/l) caused marked increases
      in serosal to mucosal net flux and efflux of Na(+). Serosal application of
      guanylin over the same dose range caused similar large increases in net serosal
      to mucosal (S-->M) Na(+) and Cl(-) flux as well as Na(+) efflux. Responses of
      Na(+) influx were small and inconsistent. When frog skin was bathed on the
      serosal side with Cl(-)-free Ringer's solution mucosal application of guanylin
      stimulated large efflux and S-->M net fluxes of Na(+). Serosal treatment yielded
      large Na(+) effluxes and S-->M Na(+) and Cl(-) net fluxes. When frog skin serosal
      surfaces were bathed with Na(+)- free Ringer's solution mucosal guanylin
      treatment had no effect but serosal treatment produced large S-->M Cl(-) net
      fluxes.

PMID- 10958998
TI  - Uncoupling of proopiomelanocortin (POMC) fragments is related to self-injury.
AB  - Proopiomelanocortin (POMC) contains several interesting, behaviorally active
      peptides. Release patterns of these fragments have been related to bizarre
      episodes of self-injurious behavior (SIB) among autistic individuals. Moreover,
      elevation in beta-endorphin (betaE) but not ACTH levels was associated with a
      positive response to an acutely administered, centrally acting opioid blocker
      among autistic individuals exhibiting SIB. In the present study, POMC fragments
      were measured in 12 self-injurious patients before and after long term (3 month)
      treatment with an opiate blocker naltrexone (NTX). POMC fragments were sampled
      from blood collected at the beginning of the baseline and placebo-controlled
      treatment phases of the study. Results indicated that the co-release (coupling)
      of POMC fragments were stable over time and the profile of POMC fragments in
      plasma predicted the effectiveness of a CNS acting drug in autistic subjects who
      self-injure.

PMID- 10958999
TI  - Melanocortin signaling is decreased during neurotoxin-induced transient
      hyperphagia and increased body-weight gain.
AB  - Hypothalamic neuropeptides play critical roles in the regulation of feeding
      behavior and body weight (BW). Disruption of signaling in the ventromedial
      nucleus by microinjection of the neurotoxin, colchicine (COL), produces transient
      hyperphagia with corresponding BW gain lasting for 4 days. Because the
      melanocortin system exerts an inhibitory control on food intake, we hypothesized
      that hyperphagia in COL-treated rats is due to decreased melanocortin-induced
      restraint on feeding. Melanocortin restraint is exerted through alpha
      melanocortin-stimulating hormone derived from proopiomelanocortin (POMC) and is
      antagonized by agouti-related peptide produced in neurons located in the arcuate
      nucleus (ARC). COL (4 microg/0.5 microl saline) or saline was microinjected
      bilaterally into the ventromedial nucleus of adult male rats. In conjunction with
      BW gain, blood leptin levels were elevated, whereas POMC mRNA in the ARC was
      significantly decreased in COL-injected rats. Levels of alpha-melanocortin
      stimulating hormone were also decreased in the micropunched paraventricular
      nucleus, dorsomedial nucleus, and perifornical hypothalamus, sites implicated in
      the control of food intake. That diminution in melanocortin signaling underlies
      hyperphagia was supported by the observation that intracerebroventricular
      injection of the MC3/MC4 melanocortin receptor agonist, MTII, prevented the
      hyperphagia and BW gain. Surprisingly, however, mRNA levels of the orexigenic
      peptide agouti-related peptide in the ARC were decreased perhaps due to the
      action of elevated leptin. These results show that transient hyperphagia and BW
      gain induced by disruption of signaling in the ventromedial nucleus results from
      two neurochemical rearrangements: development of leptin resistance in POMC
      neurons and diminution in melanocortin signaling as reflected by decreased POMC
      gene expression in the ARC and decreased availability of alpha-melanocortin
      stimulating hormone for release in feeding relevant sites.

PMID- 10959000
TI  - Structure-activity studies of alpha-melanotropin fragments on cAMP production in
      striatal slices.
AB  - In this work, we characterized the active site in the alpha-melanotropin hormone
      (alpha-MSH) sequence responsible for the enhancement of cAMP production in
      incubated striatal slices by using different alpha-MSH fragments. We also
      analyzed the effects of the co-incubation of the SCH23390, a dopaminergic D(1)
      antagonist, with the MSH fragments, to study the involvement of the D(1) receptor
      on this induction. A rise was observed in the levels of cAMP after addition of
      the 6 microM fragments MSH((1-10)), and 0.6 and 6 microM MSH((5-13)); however,
      the values were lower than those induced by 6 microM alpha-MSH. On the contrary,
      the addition of MSH((9-13)), MSH((7-11)), or MSH((6-9)) did not affect the cAMP
      content. The presence of 10 microM SCH23390 blocked the effect of the fragments
      on cAMP production. We conclude that the biologic activity of alpha-MSH, as
      observed through the levels of cAMP, declines when the length of its polypeptide
      chain is shortened, and that the presence of glutamic acid in the molecule, as
      well as the core sequence, are of importance for fragments' activity.

PMID- 10959001
TI  - Cathepsin B inhibitory peptides derived from beta-casein.
AB  - Two cathepsin B inhibitory peptides were isolated from a commercial pancreatic
      digest of casein. The peptides were identified as the Pro-Phe-Pro-Gly-Pro-Ile and
      the Gly-Pro-Phe-Pro-Ile corresponding to the sequence 61-66 and 203-207 of bovine
      beta-casein. These peptides showed competitive inhibition for cathepsin B with
      the K(i) values of 2.31 and 3.30 mM, respectively. Two related analogues, Tyr-Pro
      Phe-Pro-Gly-Pro-Ile and Val-Tyr-Pro-Phe-Pro-Gly-Pro-Ile, were synthesized but
      their cathepsin B inhibitory activity was not detected.

PMID- 10959002
TI  - Vasopressin deficiency provides evidence for separate circadian oscillators of
      activity and temperature.
AB  - Vasopressin-containing Long-Evans and vasopressin-deficient Brattleboro rats were
      maintained in individual cages while telemetered activity (AC) and body
      temperature (BT) data were collected. Rats were initially exposed to a 12 h/12-h
      light/dark cycle (photic zeitgeber) and were allowed ad-libitum access to food
      and water. Daily feeding, care, and handling (nonphotic zeitgebers) occurred at
      the beginning of the second hour of the dark cycle. After a 14-day habituation
      period, rats were subjected to continuous light (LL) or dark (DD) and nonphotic
      cues were presented irregularly. During the habituation period, both strains
      exhibited clear 24-h circadian rhythms of AC and BT. In LL or DD, photic cues
      were removed and nonphotic cues were presented irregularly. There was a shift in
      the rhythm for Long-Evans animals to 26 h for both AC and BT in LL and 24.6 h in
      DD. Feeding, care, and handling were seen as minor artifact. In Brattleboro rats,
      although there were robust 26-h and 24.6-h circadian rhythms of AC in the LL and
      DD, respectively, BT data were inconsistent and showed sporadic fluctuations. In
      the BT rhythm of Brattleboro animals, strong peaks were associated with feeding,
      care, and handling times and trough periods were characterized by a dramatic drop
      in temperature. This experiment demonstrates that AC and BT are controlled by
      separate oscillators. In addition, the importance of vasopressinergic fibers in
      the control of circadian rhythms of BT is evidenced by the loss of circadian
      rhythms in animals lacking these functional fibers when exposed to free-running
      paradigms where there is no entrainment of photic or nonphotic oscillators.

PMID- 10959003
TI  - PACAP38 and PACAP27 administered intracerebroventricularly have an opposite
      effect on LH secretion.
AB  - The effect of PACAP38 on the LH surge and ovulation was compared with that of
      PACAP27 and VIP in the same model. The peptides were administered
      intracerebroventricularly before the critical period of the proestrous stage.
      PACAP38 was able to inhibit ovulation and to prevent the preovulatory LH surge;
      however, PACAP27 did not inhibit the ovulation and VIP inhibited the ovulation in
      2/11 animals. In those animals of the last two groups in which ovulation
      occurred, the preovulatory LH surge was higher than in control rats. It is
      speculated that the opposite effect of PACAP38 and PACAP27 on the preovulatory LH
      surge and ovulation is possibly mediated through different receptors.

PMID- 10959004
TI  - Presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its
      relaxant activity in the rectum of a teleost, the stargazer, Uranoscopus
      japonicus.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide and
      a member of the secretin/glucagon superfamily of peptides that include vasoactive
      intestinal polypeptide. PACAP is not only present in the central nervous system
      but also in peripheral organs, such as the gastrointestinal tract, gonads and
      adrenal glands, and plays various roles in mammals. Recently, we isolated and
      characterized PACAP, which is very similar to PACAP of mammalian origin, from the
      brain of a teleost, the stargazer, Uranoscopus japonicus. In the present study,
      the expression of PACAP mRNA was detected in the stargazer rectum using the
      reverse transcriptase/polymerase chain reaction (RT-PCR) method. The distribution
      of PACAP-like immunoreactivity in the rectum was also examined
      immunohistochemically, using an antiserum raised against PACAP 27, and PACAP-like
      immunoreactive neuronal cell bodies and fibers were found in the myenteric
      plexuses and the smooth muscle layers of the rectum. The present study also
      investigated the relaxant activity of synthesized homologous PACAP on rectal
      contraction. Stargazer PACAP, like that of mammalian origin, inhibited
      contractions stimulated by acetylcholine or potassium chloride. PACAP-induced
      inhibition was not affected by preincubation with atropine, propranolol, or
      phentolamine. These results suggest that PACAP may act directly as an inhibitory
      neuropeptide in the stargazer rectum.

PMID- 10959005
TI  - New bradykinin analogs in contraction of rat uterus.
AB  - In this study, we evaluated 20 of our previously synthesized peptides on isolated
      rat uterus by Holton's procedure with minor modifications, and compared their
      activity with that assessed previously by their ability to inhibit vasodepressor
      response to exogenous bradykinin (BK) in conscious rats. We used [D-Arg(0),
      Hyp(3), Thi(5, 8), (D-Phe)(7)]BK, the B(2) antagonist of Vavrek and Stewart as a
      model when designing our analogs. We observed that, in the case of the rat uterus
      test, the activity of peptides modified by acylation of the N-terminus with
      various bulky groups depends substantially on the chemical character of the
      substituent. We also learned that, contrary to previous examples, acylation of
      the N-terminus of antagonists, which contain a sterically restricted fragment in
      the C-terminal part, may not improve their antagonistic potencies. Besides an
      improved characterization of a series BK analogs, our studies have provided new
      information on the structure-activity relationship, which in turn may be of value
      in the design of more potent and selective bradykinin antagonists. The results of
      our studies appear to support the hypothesis of others about the presence of
      different subtypes of B(2) receptors in rat uterus and blood vessels.

PMID- 10959006
TI  - Neuropeptide Y is a cotransmitter with norepinephrine in guinea pig inferior
      mesenteric vein.
AB  - Neuropeptide Y (NPY) is a cotransmitter with noradrenaline in guinea pig inferior
      mesenteric vein. Tyrosine hydroxylase-like immunoreactivity and NPY-like
      immunoreactivity were colocalized in a dense network of fibers within the
      adventitial layer of guinea-pig inferior mesenteric vein. Vasoconstrictor
      responses to electrical field stimulation (0.2-64 Hz, 0.1 ms, 12 V, for 10 s)
      appear to be mediated primarily by norepinephrine at 0.2 to 4 Hz and by NPY at 8
      to 64 Hz. NPY Y1 receptors mediate the contractile responses to both endogenous
      and exogenous NPY. Norepinephrine and NPY are involved in neuromuscular
      transmission in guinea pig mesenteric vein suggesting that the sympathetic
      nervous system requires the coordinated action of norepinephrine and NPY to serve
      capacitance.

PMID- 10959007
TI  - Anabolic-androgenic steroids affect the content of substance P and substance P(1
      7) in the rat brain.
AB  - The effects of intramuscular (i.m.) injections of nandrolone decanoate (15
      mg/kg/day), an anabolic-androgenic steroid, on the levels of substance P (SP) and
      on its N-terminal fragment SP(1-7) were examined in the male rat brain by
      radioimmunoassay. The results demonstrated that the SP immunoreactivity in
      amygdala, hypothalamus, striatum, and periaqueductal gray was significantly
      enhanced, whereas the concentration of the N-terminal fragment SP(1-7) was
      enhanced in the nucleus accumbens and in periaqueductal gray. In the striatum the
      steroid induced a decrease in the content of SP(1-7). The relevance of these
      peptides in connection with anabolic-androgenic steroid-induced aggression is
      discussed.

PMID- 10959008
TI  - A high-recovery extraction procedure for quantitative analysis of substance P and
      opioid peptides in human cerebrospinal fluid.
AB  - This study reports an improved approach for the determination of neuropeptide
      levels in human cerebrospinal fluid (CSF). The method is based on sample
      acidification followed by liquid-liquid extraction (LLE) combined with
      radioimmunoassay. It was applied to study the recovery and level of some opioid
      peptides (Met-enkephalin-Arg(6)-Phe(7) and Leu-enkephalin-Arg(6)), substance P
      and the substance P(1-7) fragment, which are all compounds known to be present in
      human CSF. The results indicated that the use of LLE highly improved the recovery
      of these peptides compared to current liquid-solid-phase extraction methods by
      using silica gel cartridges or mini-columns for ion-exchange chromatography.
      Peptides added to CSF in concentrations down to 10 fmol/ml were recovered in
      yields exceeding 80%. The mean recovery of synthetic peptides as recorded by
      radioimmunoassay in the LLE procedure was significantly improved when HCl was
      added to the sample. In contrast, when the (125)I-labeled analogues of the
      peptides were added to CSF samples, the mean recovery of the four labeled
      peptides using the LLE procedure was markedly reduced in acidified samples. We
      also found that the inclusion of HCl effectively improved the removal of proteins
      present in the samples. As an application the levels of substance P and Met
      enkephalin-Arg(6)-Phe(7) in CSF samples from patients with chronic pain
      (fibromyalgia syndrome) were measured using the new procedure. It was possible to
      confirm a significant difference in the CSF levels of both peptides when
      comparing patients and controls.

PMID- 10959009
TI  - Binding characteristics of endothelin ET(A) receptors in normal and post-mortem
      rat lung.
AB  - In control lung homogenates, optimal specific binding of [(125)I]endothelin-1 and
      minimal filter binding was achieved using 50 microg/ml bacitracin, 30 microM
      phenylmethylsulphonyl fluoride (PMSF) and 10 mM EDTA. In post-mortem tissue (8,
      16, and 32 h), no significant changes were seen in ET(A) receptor affinity (K(d))
      or number (B(max)): control and 32 h K(d) = 309 +/- 75, 225 +/- 32 pM and B(max)
      = 173 +/- 42, 185 +/- 17 fmol/mg protein, respectively. Autoradiographic binding
      sites for [(125)I]endothelin-1 were densely expressed on bronchiolar smooth
      muscle and parenchyma with moderate binding on epithelium and blood vessels.
      Histologic sections of post-mortem lung showed minimal deterioration of
      structures expressing ET(A) binding sites. Hence the ET(A) receptor is stable in
      the rat lung for up to 32 h post-mortem.

PMID- 10959010
TI  - Correlation between apolipoprotein B and endothelin-1-induced vasoconstriction in
      humans.
AB  - Low-density lipoprotein (LDL) concentrations have been linked to altered
      responses to endogenous vasodilators and vasoconstrictors. We evaluated
      retrospectively the relationship between LDL and vasoconstrictor (endothelin-1,
      phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy
      volunteers with apolipoprotein B and LDL levels in the normal range. In contrast
      to phenylephrine, changes in forearm vascular resistance induced by endothelin-1
      were correlated with apolipoprotein B, LDL, and total cholesterol concentrations
      in women but not in men. These findings might suggest that lipids may increase
      vascular tone through both impaired endothelial vasodilation and increased
      vasoconstriction to endothelin-1 at least in women.

PMID- 10959011
TI  - Effects of atrial natriuretic peptide in the gut.
AB  - The intestinal tract is a target organ for atrial natriuretic peptide (ANP),
      characterized by various biologic activities, immunoreactivity, as well as
      specific binding sites for ANP. A review of previous studies reveals that ANP is
      an important regulator of water and nutrient intake, which acts via multiple
      signaling pathways including activation of guanylyl cyclase to produce its
      biologic responses. As a regulator, the peptide locally controls hydrosaline
      balance and acute systemic effects. Therefore, ANP could also act as a local
      mediator or paracrine effector of intestinal function.

PMID- 10959012
TI  - In this issue

PMID- 10959013
TI  - The resuscitation greats. Friedrich Trendelenburg (1844-1924).

PMID- 10959014
TI  - High dose versus standard dose epinephrine in cardiac arrest - a meta-analysis.
AB  - In the management of cardiac arrest there is ongoing controversy concerning the
      optimal dose of epinephrine. To obtain the best available evidence regarding the
      current optimal dose, we performed a meta-analysis. We searched the Medline
      database online and reviewed citations in relevant articles to identify studies
      that met preset inclusion criteria (prospective, randomized, double-blind). Five
      trials were identified. The pooled odds ratio for return of spontaneous
      circulation favours the experimental dose. The pooled odds ratio for hospital
      discharge failed to demonstrate a statistically significant beneficial effect of
      high and/or escalating doses of epinephrine in comparison with standard dose of
      epinephrine. The possibility that patients who have already sustained
      irreversible neurologic injury will be resuscitated carries potential adverse
      social and economic implications.

PMID- 10959015
TI  - Long-term prognosis among survivors after in-hospital cardiac arrest.
AB  - AIM: To describe mortality and morbidity in the 2 years after discharge from
      hospital among patients surviving an in-hospital cardiac arrest. PATIENTS: All
      patients over a 2-year period who survived in-hospital cardiac arrest and could
      be discharged from hospital. SETTING: Sahlgrenska University Hospital in
      Goteborg. METHODS: The patients were followed prospectively for 2 years after
      discharge from hospital and evaluated in terms of mortality and morbidity and
      cerebral performance categories (CPC) score. CPC score was estimated by reference
      to the case notes. RESULTS: In all, 216 patients suffered in-hospital cardiac
      arrest and the resuscitation team was alerted: 79 patients (36.6%) were
      discharged alive. Among these 79 patients, 26.6% died, 7.8% developed a confirmed
      myocardial infarction and 1.3% developed a stroke during the subsequent 2 years.
      Among patients with a CPC score >1 at discharge (n=15), mortality was 66.7% as
      compared with 17.5% among patients with a CPC score of 1 (P=0.0008). Among
      patients aged >68 years (median) mortality was 39.5 versus 14.6% among patients <
      or =68 years of age (P=0.002). In all, 71% required rehospitalization for any
      reason and 51% required rehospitalization due to a cardiac cause. At hospital
      discharge 81% of all survivors had a CPC score of 1 and among survivors 2 years
      later 89% had a CPC score of 1. CONCLUSION: Among survivors of in-hospital arrest
      approximately 75% survived the subsequent 2 years. Survival was related to age
      and CPC score at discharge. Among survivors after 2 years the vast majority had a
      relatively good cerebral performance.

PMID- 10959016
TI  - Outcome following cardiopulmonary resuscitation in the neonate requiring
      ventilatory assistance.
AB  - BACKGROUND: there is limited data regarding the clinical characteristics and
      outcome of the neonate requiring ventilatory assistance who develops persistent
      bradycardia (PB) requiring cardiopulmonary resuscitation (CPR). OBJECTIVES: (1)
      to determine the percentage of newborn infants requiring respiratory assistance
      who develop PB and require CPR as part of resuscitation; (2) the associated
      clinical events; and (3) the short term outcome. METHODS: the medical charts of
      infants admitted to a neonatal intensive care unit who developed PB, defined as a
      heart rate <80 beats/min requiring CPR, were retrospectively reviewed. RESULTS:
      for 3 years, 39 (2.6%) of 1485 infants exhibited 62 episodes of PB requiring CPR;
      this represents 5.6% of 695 intubated infants. Fourteen (36%) infants rapidly
      responded to chest compressions only with restoration of heart rate within 2 min;
      termed brief CPR. None died in-hospital. Twenty-five (64%) infants required
      prolonged chest compressions, i.e. >2 min (termed prolonged CPR); 21 also
      received epinephrine. The median postnatal age at onset of CPR was 20 days (range
      1-148 days) and the duration of CPR was 10 min (range 3-73 min). The more common
      medical conditions that may have contributed to the PB included severe
      bronchospasm associated with chronic lung disease (CLD) (n=6), shock associated
      with sepsis (n=4) and necrotizing enterocolitis (NEC) (n=2), pneumothorax (n=2),
      inadequate or improper ventilation (n=3), other (n=8). Nineteen (76%) infants
      died: 13 within 24 h of the event and six from 3 to 194 days following CPR. At 18
      months follow-up, four of the six infants evaluated have a moderate to severe
      neurodevelopmental deficit. Of the nine infants requiring brief CPR who were
      evaluated, five are developing normally and four have a moderate to severe
      neurodevelopmental deficit. CONCLUSION: CPR in the neonate who requires
      ventilatory assistance is not uncommon. When brief in nature, mortality is low
      and short-term outcome is likely to be determined by the underlying medical
      condition. When CPR is prolonged, mortality is high and short-term outcome is
      poor.

PMID- 10959017
TI  - Termination of recent-onset atrial fibrillation/flutter in the emergency
      department: a sequential approach with intravenous ibutilide and external
      electrical cardioversion.
AB  - Safety and effectiveness are the goals in treating patients with arrhythmias. In
      an open prospective study, we observed the efficacy and safety of up to 2 mg
      intravenous ibutilide, a new class III antiarrhythmic agent in haemodynamically
      stable patients presenting in the emergency department (ED) with symptoms of
      recent-onset (<48 h) atrial fibrillation/flutter. Arrhythmia termination within
      90 min, haemodynamic parameters and proarrhythmic effects were assessed. Non
      responders to the ibutilide infusion underwent external electrical cardioversion.
      We included 51 patients. In 31 patients therapeutic intervention with intravenous
      ibutilide was successful within 90 min (61%). In another seven patients
      conversion to sinus rhythm occurred after 90 min without any other intervention
      (14%). Blood pressure remained stable and no relevant proarrhythmic effects were
      observed. The 13 patients who did not respond to ibutilide treatment underwent
      successful external electrical cardioversion. The overall conversion rate was
      100%. Forty-seven patients (92%) were discharged within a median of 9 h and
      managed as outpatients. In conclusion, in haemodynamically stable patients with
      recent-onset atrial fibrillation/flutter intravenous ibutilide and external
      electrical cardioversion for conversion to sinus rhythm turned out to be
      effective and safe. The short duration of admission makes this strategy
      attractive for use in the ED.

PMID- 10959018
TI  - Cardiopulmonary resuscitation training for students of odontology: skills
      acquisition after two periods of learning.
AB  - INTRODUCTION: Although life threatening emergencies in dental practice are not
      frequent, dentists have to be competent in providing basic life support (BLS).
      OBJECTIVES: The aim of this work was to study the level of skills acquisition
      among dentistry students in two different periods of one rescuer-BLS training, a
      first short practice training of 2 h followed by 8 h of practice over a period of
      2 months. METHODS: One hundred and sixteen second-year undergraduate students of
      Anesthesiology at the Dental School of the Complutense University in Madrid were
      tested at the end of the two periods of learning using a recording manikin with a
      validated scoring system (Laerdal Resusci-Anne). This manikin recorded the
      percentage of adequate chest compressions and insuflations, rate of chest
      compressions and the causes of error in each case. RESULTS: Final global results
      were, 51.66+/-3.0% adequate chest compressions; and 54.44+/-3.61% adequate
      insuflations. The kinds of errors where different in both tests were, wrong hand
      position (26.92+/-2.96 vs. 12.29+/-2.40%, P<0.001); excessive compressions
      (27.71+/-2.90 vs. 16.02+/-2.33%, P<0.05); and weak compressions (23.28+/-3.24 vs.
      16.77+/-2.57%, P<0.05). Regression analysis found a positive correlation among
      excessive compression, height and weight (P<0.001) and a negative correlation
      between weak compression, height and weight (P<0.001). CONCLUSIONS: The poor
      overall results, although similar to those shown in the literature, have made us
      question the validity of our methods of teaching BLS. We were able to establish a
      correlation between demographic and sociocultural variables with the typical
      errors, and to begin the process of improving our teaching methods.

PMID- 10959019
TI  - A comparison of manikin CPR performance by lay persons trained in three
      variations of basic life support guidelines.
AB  - This paper reports on a randomised controlled trial comparing the acquisition and
      retention of cardiopulmonary resuscitation (CPR) skills by lay persons trained in
      three variations of basic life support. Training was provided either in 1992
      European Resuscitation Council (ERC) guidelines, or in the 1997 International
      Liaison Committee on Resuscitation (ILCOR) Advisory Statement (adopted with minor
      revisions as 1998 ERC guidelines), and an American Heart Association 'call first'
      version of the 1997 ILCOR statement. Evaluation of manikin CPR using the
      established Cardiff tests (CARE and VIDRAP) showed that 51% of those trained in
      the current ILCOR guidelines performed effectively compared with 38% trained in
      the ERC 1992 guidelines and 25% trained in the 'call first' variation (P<0.01).
      Whilst the current ERC and ILCOR guidelines appeared easiest to learn, retention
      at 6 months was poor (14% effective) irrespective of method.

PMID- 10959020
TI  - The effect of prior hypothermia on the physiological response to norepinephrine.
AB  - OBJECTIVE: this study determines the effect of prior hypothermia on the
      cardiovascular responses to norepinephrine (NE) after rewarming. METHODS: the
      experiment was a 2x2 controlled design with four groups of feline animals. The
      two variables were the presence or absence of previous cooling, and the use or
      non-use of NE after rewarming. During the 'cooling' phase, animals were either
      cooled using an external arterial-venous femoral shunt to 30 degrees C or
      maintained at 37 degrees C. After 'rewarming' animals were stratified to receive
      either NE at rates to deliver 0.2, 1.0 or 5 microg/kg per h or normal saline
      infusions. Animals were instrumented to measure mean arterial pressure (MAP) and
      cardiac output (CO) and systemic vascular resistance (SVR) was calculated.
      RESULTS: there were no differences between groups at baseline and low dose NE
      (0.2 microg/kg per min). At 1.0 microg/kg per min, NE caused a significant
      increase in CO (P<0.01) and no effect of MAP or SVR in the rewarmed animals when
      compared with normothermic controls. In rewarmed animals 5.0 microg/kg per min NE
      caused a significant increase in CO (P<0.01) and no effect on MAP or SVR. In
      normothermic controls there was a significant increase in SVR (P=0.02) and MAP
      (P=0.05) and no effect on CO. CONCLUSION: this study shows that the effect of
      prior hypothermia on cardiovascular responses to moderate and high doses of NE is
      an improved CO with no affect on SVR and MAP. This could alter the clinical
      utility of NE in this situation.

PMID- 10959022
TI  - A simple strategy to improve first breath oxygen delivery by self inflating bag.
AB  - The text book of Pediatric Advanced Life Support of the American Heart
      Association recommends that a reservoir is used with a self inflating bag valve
      device. The figure in the book suggests that if such a device is connected to an
      oxygen supply, the oxygen will fill the bag first and then go on to fill the
      reservoir. However the valve structure of the self-inflating device does not
      permit active entry of oxygen into the bag, unless the bag is deflated and
      allowed to reinflate, drawing oxygen from the reservoir. We did this study to
      test the concentration of oxygen delivered in the first few breaths with the help
      of a Miniox-III oxygen monitor probe (MSA Medical Products, Pittsburgh, PA 15230)
      inserted into a self inflating bag (AMBU). Twenty-one percent oxygen is delivered
      with first breath and it rose to 42 and 58% with the second and third inflations,
      respectively. Eighty percent oxygen was achieved after eight reinflation cycles.
      We developed a formula to calculate the concentration of oxygen in the bag after
      each inflation effort, assuming that there was no passive diffusion of oxygen. We
      suggest that compressing the bag 8-12 times prior to putting the mask to the face
      of the patient will allow 80% oxygen to be delivered with first breath.

PMID- 10959021
TI  - Effects of increased oxygen breathing in a volume controlled hemorrhagic shock
      outcome model in rats.
AB  - It is believed that victims of traumatic hemorrhagic shock (HS) benefit from
      breathing 100% O(2). Supplying bottled O(2) for military and civilian first aid
      is difficult and expensive. We tested the hypothesis that increased FiO(2) both
      during severe volume-controlled HS and after resuscitation in rats would: (1)
      increase blood pressure; (2) mitigate visceral dysoxia and thereby prevent post
      shock multiple organ failure; and (3) increase survival time and rate. Thirty
      rats, under light anesthesia with halothane (0. 5% throughout), with spontaneous
      breathing of air, underwent blood withdrawal of 3 ml/100 g over 15 min. After HS
      phase I of 60 min, resuscitation phase II of 180 min with normotensive
      intravenous fluid resuscitation (shed blood plus lactated Ringer's solution), was
      followed by an observation phase III to 72 h and necropsy. Rats were randomly
      divided into three groups of ten rats each: group 1 with FiO(2) 0.21 (air)
      throughout; group 2 with FiO(2) 0.5; and group 3 with FiO(2) 1.0, from HS 15 min
      to the end of phase II. Visceral dysoxia was monitored during phases I and II in
      terms of liver and gut surface PCO(2) increase. The main outcome variables were
      survival time and rate. PaO(2) values at the end of HS averaged 88 mmHg with
      FiO(2) 0.21; 217 with FiO(2) 0.5; and 348 with FiO(2) 1. 0 (P<0.001). During HS
      phase I, FiO(2) 0.5 increased mean arterial pressure (MAP) (NS) and kept arterial
      lactate lower (P<0.05), compared with FiO(2) 0.21 or 1.0. During phase II, FiO(2)
      0.5 and 1. 0 increased MAP compared with FiO(2) 0.21 (P<0.01). Heart rate was
      transiently slower during phases I and II in oxygen groups 2 and 3, compared with
      air group 1 (P<0.05). During HS, FiO(2) 0.5 and 1.0 mitigated visceral dysoxia
      (tissue PCO(2) rise) transiently, compared with FiO(2) 0.21 (P<0.05). Survival
      time (by life table analysis) was longer after FiO(2) 0.5 than after FiO(2) 0.21
      (P<0. 05) or 1.0 (NS), without a significant difference between FiO(2) 0. 21 and
      1.0. Survival rate to 72 h was achieved by two of ten rats in FiO(2) 0.21 group
      1, by four of ten rats in FiO(2) 0.5 group 2 (NS); and by four of ten rats of
      FiO(2) 1.0 group 3 (NS). In late deaths macroscopic necroses of the small
      intestine were less frequent in FiO(2) 0.5 group 2. We conclude that in rats, in
      the absence of hypoxemia, increasing FiO(2) from 0.21 to 0.5 or 1.0 does not
      increase the chance to achieve long-term survival. Breathing FiO(2) 0.5, however,
      might increase survival time in untreated HS, as it can mitigate hypotension,
      lactacidemia and visceral dysoxia.

PMID- 10959023
TI  - Neonatal resuscitation course experience in Turkey.

PMID- 10959024
TI  - Oxygen toxicity in resuscitation.

PMID- 10959026
TI  - Life-threatening arrhythmias and therapy.

PMID- 10959027
TI  - Combination ICD and drug treatments-best options.

PMID- 10959028
TI  - Revisiting established medical options - antiarrhythmic drugs and beta-blocker
      combinations.

PMID- 10959029
TI  - Primary prevention of sudden cardiac death - the role of antiarrhythmic drug
      therapy.

PMID- 10959030
TI  - Alzheimer's disease and related dementias: the road to intervention.

PMID- 10959031
TI  - Molecular mechanisms of late life dementias.
AB  - A brief overview of the molecular pathology of dementia of the Alzheimer type
      (DAT), frontotemporal dementias (FTD), and Lewy body dementias (LBD) is preceded
      by a discussion of the evolutionary biological basis for the types of gene action
      responsible for the emergence of late life dementias. The beta amyloid cascade
      theory of the pathogenesis of DAT still predominates, but possible upstream
      events are being explored. Some familial forms of FTD have been shown to result
      from dominant mutations in the microtubular associated protein tau. A key element
      in pathogenesis is a shift in the ratios of various isoforms. Rare forms of
      Parkinson disease have been associated with dominant mutations in alpha
      synuclein, a protein of probable importance for synaptic plasticity. Aberrations
      in the metabolism of this protein (which is found in Lewy body fibrillar
      material) may therefore be of importance to the genesis of some LBD cases.

PMID- 10959032
TI  - Oxidative processes in Alzheimer's disease: the role of abeta-metal interactions.
AB  - Alzheimer's disease is characterized by signs of a major oxidative stress in the
      neocortex and the concomitant deposition of Amyloid beta (Abeta). Abeta is a
      metalloprotein that binds copper, and is electrochemically active. Abeta converts
      molecular oxygen into hydrogen peroxide by reducing copper or iron, and this may
      lead to Fenton chemistry. Hydrogen peroxide is a freely permeable prooxidant that
      may be responsible for many of the oxidative adducts that form in the Alzheimer
      affected brain. The electrochemical activity of various Abeta species correlates
      with the peptides' neurotoxicity in cell culture, and participation in the
      neuropathology of Alzheimer's disease. These reactions present a novel target for
      Alzheimer therapeutics.

PMID- 10959033
TI  - Role of presenilin in gamma-secretase cleavage of amyloid precursor protein.
AB  - Cerebral accumulation of the amyloid beta-protein (Abeta) is an early and
      invariant event in the pathogenesis of Alzheimer's disease (AD). Mutations in the
      presenilin (PS) 1 and 2 genes that increase production of the highly
      amyloidogenic Abeta(42) are the most common cause of familial AD. Deletion of PS1
      in mice reduces Abeta generation, indicating that PS1 mediates the last step in
      the generation of Abeta from beta-amyloid precursor protein (APP) by the
      unidentified gamma-secretase. Mutating either of two conserved transmembrane
      aspartates in PS1 significantly reduced Abeta production and increased the APP C
      terminal fragments that are gamma-secretase substrates. These results indicate
      that PS1 is either a unique diaspartyl cofactor for gamma-secretase or is itself
      gamma-secretase. Furthermore, studies on the gamma-secretase-like proteolytic
      processing of Notch and Ire1 suggest a common mechanism for the involvement of
      PS1 in intramembrane proteolysis of membrane proteins.

PMID- 10959034
TI  - The molecular genetics of the tauopathies.
AB  - The identification of mutations in the tau gene in frontotemporal dementia and
      Parkinsonism linked to chromosome 17 (FTDP-17) demonstrated that there is a
      direct link between tau dysfunction and neurodegeneration. At least 11 missense
      mutations and a three base pair deletion (DeltaK280) have been identified in
      exons 9-13. Additionally, five splice site mutations have been found in intron
      10. The different FTDP-17 mutations have multiple effects on the biology and
      function of tau. These varied pathogenic mechanisms likely explain the wide range
      of clinical and neuropathological features observed in different families with
      FTDP-17. In addition to the tau mutations, a common extended haplotype in the tau
      gene also appears to be a risk factor in the development of the apparently
      sporadic tauopathies progressive supranuclear palsy (PSP) and corticobasal
      degeneration (CBD). The mechanism by which this common variability in the tau
      gene influences the development of these neurodegenerative diseases is unclear;
      however, it further suggests a central role for tau in the pathogenesis of
      several neurodegenerative conditions including Alzheimer's disease (AD).

PMID- 10959035
TI  - alpha2-macroglobulin in late-onset Alzheimer's disease.
AB  - alpha2-macroglobulin (alpha(2)M) is an abundant plasma protein similar in
      structure and function to a group of proteins called alpha-macroglobulins.
      alpha(2)M is also produced in the brain where it binds multiple extracellular
      ligands and is internalized by neurons and astrocytes. In the brain of
      Alzheimer's disease (AD) patients, alpha(2)M has been localized to diffuse
      amyloid plaques. alpha(2)M also binds soluble beta-amyloid, of which it mediates
      degradation. However, an excess of alpha(2)M can also have neurotoxic effects.
      Based on genetic evidence, is now recognized as one of the two confirmed late
      onset AD genes. As for the three early onset genes (the amyloid beta-protein
      precursor and the two presenilins) and for the other late onset gene (ApoE), DNA
      polymorphisms in the A2M gene associated with AD result in significantly
      increased accumulation of amyloid plaques in AD brains. These data support an
      important role for A2M in AD etiopathology.

PMID- 10959037
TI  - Emerging neuroprotective strategies for Alzheimer's disease: dietary restriction,
      telomerase activation, and stem cell therapy.
AB  - The molecular, biochemical and cellular events that result in synaptic
      dysfunction and neuronal degeneration in the brain in Alzheimer's disease (AD)
      are becoming known. Age-related increases in cellular oxidative stress, and
      impairment of energy metabolism, result in disruption of neuronal calcium
      homeostasis and increased vulnerability of neurons to excitotoxicity and
      apoptosis. Inherited forms of AD that result from mutations in the beta-amyloid
      precursor protein (APP) and presenilins accelerate the neurodegenerative cascade
      by increasing production and deposition of neurotoxic forms of amyloid beta
      peptide and by perturbing calcium homeostasis. Dietary restriction (DR; reduced
      calorie intake with maintained nutrition) extends life span of rodents and
      (probably) humans. DR increases resistance of neurons to dysfunction and
      degeneration, and improves behavioral outcome, in experimental models of AD and
      other age-related neurodegenerative disorders by a mechanism involving a mild
      stress response. Telomerase, a specialized reverse transcriptase, has been
      proposed to possess anti-aging properties. The catalytic subunit of telomerase
      (TERT) is expressed in neurons throughout the brain during development, but is
      absent from neurons in the adult brain. TERT exhibits neuroprotective properties
      in experimental models of neurodegenerative disorders suggesting that
      manipulations that induce telomerase in neurons may protect against age-related
      neurodegeneration. Finally, the exciting and exploding field of stem cell
      research suggests methods for replacing damaged or lost brain cells in an array
      of neurological disorders.

PMID- 10959036
TI  - The pervasiveness of interleukin-1 in alzheimer pathogenesis: a role for specific
      polymorphisms in disease risk.
AB  - Interleukin-1 (IL-1) has been implicated as a key molecule in Alzheimer
      pathogenesis based on findings of an IL-1 overexpression in Alzheimer brain that
      is directly related to plaque progression and tangle formation, and on findings
      that IL-1 induces excessive synthesis, translation, and processing of neuronal
      beta-amyloid precursor protein (betaAPP) as well as synthesis of most known
      plaque-associated proteins. In addition, IL-1 activates astrocytes, with the
      important consequence of overexpression of the neuritogenic cytokine S100beta and
      overgrowth of dystrophic neurites in neuritic plaques. As further evidence of the
      importance of IL-1 in Alzheimer pathogenesis, two new genetic studies of
      inheritance of specific polymorphisms in IL-1 genes in Alzheimer and control
      patients show that homozygosity for a specific IL-1A gene polymorphism at least
      triples risk for development of Alzheimer's disease. This increase is associated
      with earlier age of onset. Homozygosity for this polymorphism plus another in the
      IL-1B gene further increases risk.

PMID- 10959038
TI  - Post-menopausal estrogen deprivation and Alzheimer's disease.
AB  - Estrogen deprivation has been implicated as a risk factor in Alzheimer's disease
      (AD) as epidemiological data suggests that estrogen replacement therapy can
      protect against the onset, and progression of the disease. Biochemical data
      suggests that estrogen exerts its affect through the processing of the amyloid
      precursor protein to beta-amyloid which is deposited in the brains of patients
      with AD. The effects of estrogens may be more widespread, however, as it has been
      implicated in the maintenance of neuronal architecture and protection from free
      radicals. This review aims to discuss the various roles of estrogen in the
      development of AD.

PMID- 10959039
TI  - Conditional gene targeting and its application in the skin.
AB  - The knockout mouse is one of the most useful experimental animal systems in which
      to clarify functions of identified genes in vivo. Numerous knockout mice have
      been produced, and studies in these models have revealed new aspects in various
      biological fields. In fair cases, however, mice died during embryogenesis due to
      complete gene disruption, making it difficult to elucidate functions of given
      genes in adulthood. To avoid this, conditional gene targeting has been performed
      and shown to be effective on numerous cases. Here, we will overview established
      strategies for conditional gene targeting and present the results of our recent
      studies using the Cre/loxP system in the skin.

PMID- 10959040
TI  - Adherence characteristics and susceptibility to antimicrobial agents of
      Staphylococcus aureus strains isolated from skin infections and atopic
      dermatitis.
AB  - We examined the adherence characteristics and susceptibility to various
      antimicrobial agents of 130 strains of Staphylococcus aureus isolated from
      infective skin lesions and 135 strains of S. aureus isolated from non-infective
      eczematous lesions of atopic dermatitis (AD) patients. The isolation rate of
      methicillin-resistant S. aureus (MRSA) was 27.7% in strains from clinical sources
      excluding AD and 31.1% in those from AD. Coagulase type II strains were most
      frequently observed in MRSA strains isolated from all sources excluding AD, and
      coagulase type III strains were most frequently observed in those isolated from
      AD. We proposed that antimicrobial treatment for AD patients should be carefully
      designed to prevent MRSA infection. Plasma coagulation ability was lowest in S.
      aureus strains isolated from abscesses, suggesting that the lower production of
      fibrin observed in abscesses may assist the infiltration of neutrophils into skin
      tissues and that a decrease in plasma coagulation ability may enable abscess
      formation. Adherence to polypropylene tubes with slime production was most
      evident in S. aureus strains isolated from felon and least evident in those
      isolated from cellulitis and lymphangitis. Tube adherence was characteristic of
      the S. aureus strains attached to superficial skin tissues, but not necessarily
      for strains that had infiltrated the deep skin tissues. Fusidic acid demonstrated
      significant antimicrobial activity against the MRSA strains, but rifampicin was
      the strongest antimicrobial agent.

PMID- 10959041
TI  - Cornified cell envelope formation is distinct from apoptosis in epidermal
      keratinocytes.
AB  - In order to maintain epidermal structural homeostasis, keratinocytes need to
      modulate their proliferation, differentiation, and cell death. Although terminal
      differentiation of keratinocytes is characterized by cornified cell envelope (CE)
      formation and one major mechanism of cell death is apoptosis, the precise
      relationship between these processes remains obscure. Using normal human cultured
      keratinocytes (NHK), we compared A23187-induced CE formation and ultraviolet B
      irradiation (UVB)-induced apoptosis. A23187 stimulated CE formation in 1 mM
      Ca(2+)-pretreated NHK cells. CE formation was detected by 1 h and the maximal
      induction was observed at 6 h. Morphological analysis using acridine orange
      staining revealed that UVB-irradiated NHK cells show distinctive round,
      homogeneous fragmented nuclear beads, a characteristic feature of apoptotic
      cells, while A23187-treated cells showed enlarged nuclei with weak chromatin
      staining, which is not typical of apoptosis. The UVB-irradiated NHK cells did not
      show CE formation. Caspase activation is a characteristic event during apoptosis.
      Although UVB irradiation increased caspase 3 activity, no increase in caspase 3
      activity was detected during A23187-induced CE formation. Multiple nucleosome
      sized fragments of DNA were observed in UVB-treated NHK cells, but not in A23187
      treated NHK cells. FACS analyses using anti-annexin V antibody and propidium
      iodide (PI) showed that UVB irradiation induced both annexin V-positive and PI
      negative early apoptotic cells and annexin V-positive and PI-positive late
      apoptotic cells. On the other hand, A23187-treated NHK cells showed only annexin
      V-negative and PI-positive non-apoptotic dying cells. Cell death assay revealed a
      significantly increased apoptotic cells in UVB-irradiated NHK cells, but not in
      A23187-treated NHK cells. UVB irradiated NHK cells showed increased cytosolic
      transglutaminase activity, while A23187-treated NHK cells showed increased
      membrane-associated transglutaminase activity. These results indicate that CE
      formation is distinct from apoptosis in epidermal keratinocytes.

PMID- 10959043
TI  - Skin barrier function in patients with completely healed atopic dermatitis.
AB  - Although it has been well established that the dry skin often seen in patients
      with atopic dermatitis shows a deranged barrier function, there is no unanimity
      of opinion as to whether the barrier in normal-appearing skin of patients with
      the disease is deranged or not. Hence, it remains unclear whether individuals
      with atopic dermatitis constitution have an intrinsic derangement of skin barrier
      function or not. To settle this problem, in the present study we examined
      transepidermal water loss and stratum corneum water content in normal appearing
      skin of the upper back of 16 patients with completely healed atopic dermatitis
      who had been free from skin symptoms for 5 years or more, 30 patients with active
      atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values
      and the stratum corneum water content values in normal-appearing skin of the
      completely healed patients were not different from the values in normal controls.
      These findings indicate that skin barrier function is not disturbed in patients
      with completely healed atopic dermatitis.

PMID- 10959042
TI  - Human malignant melanoma cells release a factor that inhibits the expression of
      smooth muscle alpha-actin.
AB  - Smooth muscle alpha-actin (SMA) is a cytoskeletal protein expressed in vascular
      smooth muscle cells, pericytes, hair follicle dermal sheaths and myofibroblasts
      which appear in the process of wound healing and tumor growth. To examine the
      effect of malignant melanoma on the expression of SMA in these non-neoplastic
      cells, we carried out immunohistochemical staining and a cell culture study.
      Conditioned medium prepared from a melanoma cell line M14 was incubated with a
      rat fibroblastic cell line 3Y1, which had been shown to express SMA. Human cells
      that had migrated from nevus tissue were also cultured either with or without M14
      conditioned medium. Immuno-histochemical staining of human melanoma tissues
      suggested that the expression of SMA was low in the vicinity of the tumor as well
      as within the tumor nodules. The conditioned medium from melanoma, but not the
      medium from control non-neoplastic cells, suppressed the expression of SMA both
      in the 3Y1 cells and human cells that migrated from the nevus. Preincubation of
      the medium with anti-platelet-derived growth factor allowed 76% recovery of SMA
      expression. These data thus imply that melanoma cells release a platelet-derived
      growth factor-like substance which has a suppressive effect on the contractile
      elements in non-neoplastic cells.

PMID- 10959045
TI  - Overview--burgeoning promise in metastasis research.

PMID- 10959044
TI  - Production of the entire extracellular domain of BP180 (type XVII collagen) by
      baculovirus expression.
AB  - Bullous pemphigoid (BP) is an acquired autoimmune skin disease, and its target
      antigens are a 230 kDa plaque protein (BP230) and a 180 kDa transmembrane protein
      with interrupted collagenous domains (BP180, type XVII collagen), which localize
      at the hemidesmosome. In this study we have attempted to express the entire
      extracellular domain of BP180 (rBP180EC) as a secreted protein by baculovirus
      expression. Seventy out of 83 BP sera (84.4%) showed positive reactivity against
      rBP180EC by immunoblot analysis, and 56 out of 83 BP sera (67.5%) were positive
      against rBP180EC by ELISA. These figures were comparable with those when a
      bacterial recombinant protein encoding the NC16a domain of BP180 (rNC16a) was
      used as an antigen source. Reactivity of BP sera against rBP180EC by ELISA was
      completely abolished or significantly reduced by immunocompetition with rNC16a in
      11 out of 14 BP sera tested, while the reactivity was not altered in the rest of
      the three sera. These findings indicate that the NC16a domain represents the
      major epitopes on the extracellular domain of BP180, although there are some
      other minor epitopes outside of NC16a which are uniquely expressed by rBP180EC.
      rBP180EC will be useful to develop a diagnostic tool for BP as well as to dissect
      a molecular role for BP180 in interactions of keratinocytes with epidermal
      basement membrane.

PMID- 10959046
TI  - Adhesion-linked kinases in cancer; emphasis on src, focal adhesion kinase and PI
      3-kinase.
AB  - Our understanding of the complex signal transduction pathways involved in
      signalling within cancer cells, between cancer cells and between cancer cells and
      their environment has increased dramatically in recent years. Here we concentrate
      on three non-receptor kinases: Src, focal adhesion kinase (FAK) and
      phosphatidylinositol 3-kinase (PI 3-kinase). These form part of a complex network
      of intracellular signals which is thought to be important in regulating cancer
      cells.

PMID- 10959047
TI  - The E-cadherin-catenin complex in tumour metastasis: structure, function and
      regulation.
AB  - E-cadherin and the associated catenin complex have been recognised as performing
      a key role in cell adhesion. Loss of cell adhesion is seen as a key step in the
      cascade leading to tumour metastasis. The ability of both extra- and
      intracellular factors to regulate E-cadherin-mediated cell adhesion in
      physiological processes has provided insight into both the interactions of the E
      cadherin-catenin complex, and possible mechanisms utilised by tumours in the
      process of metastasis. The interaction of the E-cadherin-catenin complex with
      various regulating factors, their effect on cell signalling pathways, and the
      relationship with the metastatic potential of tumours are reviewed.

PMID- 10959048
TI  - Matrix metalloproteinases: molecular aspects of their roles in tumour invasion
      and metastasis.
AB  - The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, whose
      physiological functions include tissue remodelling and embryogenesis. The
      importance of this group of proteins in the processes of tumour invasion and
      metastasis is now widely acknowledged, and has led to the search for MMP
      inhibitors for use as anticancer treatments in a clinical setting. This review
      aims to bring the reader up-to-date with current research relating to MMPs, with
      particular emphasis on emerging mechanisms of regulation of these enzymes, and
      their interaction with cell adhesion molecules. The therapeutic inhibition of
      MMPs will also be discussed.

PMID- 10959049
TI  - Individual characterisation of the metastatic capacity of human breast carcinoma.
AB  - The clinical implications of understanding the invasive and metastatic
      proclivities of an individual patient's tumour are substantial because the choice
      of systemic therapy needs to be guided by the likelihood of occult metastasis as
      well as by knowing when the metastases will become overt. Malignant potential is
      dynamic, progressing throughout the natural history of a tumour. Required of
      tumours is the development of critical phenotypic attributes: growth,
      angiogenesis, invasion and metastagenicity. Characterisation of the extent of
      tumour progression with regard to these major tumour phenotypes should allow the
      fashioning of individual therapy for each patient. To examine the clinical
      parameters and molecularly characterise the metastatic proclivity we have been
      studying a series of regionally treated breast cancer patients who received no
      systemic therapy and have long follow-up. Clinically we describe two parameters:
      metastagenicity - the metastatic proclivity of a tumour, and virulence--the rate
      at which these metastases appear. Both attributes increase with tumour size and
      nodal involvement. However, within each clinical group there is a cured
      population, even in those with extensive nodal involvement, underscoring the
      heterogeneity of breast cancers within each group and the need for further
      molecular characterisation. Using biomarkers that characterise the malignant
      phenotype we have determined that there is progression in the phenotypic changes.
      Angiogenesis and loss of nm23 are earlier events than the loss of E-cadherin, or
      abnormalities in TP53. The strongest biomarkers of poor prognosis are p53 and E
      cadherin, but even when both are abnormal 42% of node-negative patients are cured
      indicating that other determinative steps need to occur before successful
      metastases are established. Identification of these critical later events will
      further increase the efficacy of determining the malignant capacities of
      individual tumours.

PMID- 10959050
TI  - Transcriptional regulation of cell invasion: AP-1 regulation of a multigenic
      invasion programme.
AB  - The focus of this review will be on the regulation of the multigenic invasion
      programme by activator protein-1 (AP-1). Investigation of AP-1-regulated gene
      expression in transformed cells can be used to identify the genes in the
      multigenic invasion programme and to validate them as targets for diagnosis or
      therapy.

PMID- 10959051
TI  - Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic
      exploitation.
AB  - Tumour hypoxia is the result of an imbalance in oxygen supply and demand. It is
      an adverse prognostic indicator in cancer as it modulates tumour progression and
      treatment. Many genes controlling tumour biology are oxygen regulated, and new
      ones are constantly added to the growing list of hypoxia-induced genes. Of
      specific importance are hypoxia-responsive transcription factors, as they can
      modulate the expression of numerous different genes. Similarly, growth factors
      which govern the formation of new blood vessels or which control blood flow are
      vitally important for both the maintenance of the primary tumour and metastases
      at distant sites. The purpose of this review is to present an update of selected
      issues regarding hypoxia-inducible gene expression and how this affects
      prognosis, angiogenesis and metastasis. It will conclude by discussing gene
      therapy as one possible means of exploiting tumour hypoxia for the treatment of
      cancer.

PMID- 10959052
TI  - Clinical imaging of cancer metastasis.
AB  - Tumour imaging is an essential part of the practice of oncology, with a crucial
      role in screening programmes and in diagnosis and staging of established disease.
      Furthermore, the assessment of tumour size by imaging, usually with computer
      tomography (CT) scanning, is a key component in determining the tumour response
      to therapy both in clinical trials and in daily oncology practice. Techniques
      such as CT, ultrasound (US) and magnetic resonance imaging (MRI) provide high
      resolution anatomical images with detailed structural information. However, these
      imaging modalities yield limited functional information on the tumour tissues and
      often cannot distinguish residual disease from non-viable or necrotic tumour
      masses, nor can they detect minimal residual disease. In contrast,
      radiopharmaceutical imaging and, in particular, positron emission tomography
      (PET) can give some functional information about the underlying tissues. The
      possibility of refining these techniques and also the emergence of newer imaging
      modalities that can detect changes in cancers at the physiological, cellular or
      molecular levels, gives rise to the notion that these methods will have
      implications for drug development strategies and also future clinical management.
      In this review, we briefly discuss the current role of imaging in clinical
      practice, describe some of the advances in imaging modalities currently
      undergoing evaluation, and speculate on the future role of these techniques in
      developmental therapeutics programmes.

PMID- 10959053
TI  - Imaging of cancer invasion and metastasis using green fluorescent protein.
AB  - The use of green fluorescent protein to fluorescently tag tumour cells has
      allowed investigators to open the "black box" of metastasis in order to visualise
      the behaviour of tumour cells in living tissues. Analysis of cells leaving the
      primary tumour indicates that highly metastatic cells are able to polarise more
      effectively towards blood vessels while poorly metastatic cells fragment more
      often when interacting with blood. In addition, there appear to be greater
      numbers of host immune system cells interacting with metastatic tumours. After
      arresting in target organs such as the lungs or liver, most tumour cells become
      dormant or apoptose. A small fraction of the arrested cells form metastases. In
      some target organs, migration of tumour cells may enhance the ability to form
      metastases.

PMID- 10959054
TI  - Molecular detection and characterisation of circulating tumour cells and
      micrometastases in solid tumours.
AB  - The detection and molecular characterisation of circulating tumour cells (CTC)
      and micrometastases may have important prognostic and therapeutic implications.
      Because their numbers are very small, these tumour cells are not easily detected
      using conventional methods. In the last decade, numerous groups have attempted to
      detect occult tumour cells in solid malignancies using the highly sensitive
      reverse transcriptase polymerase chain reaction (RT-PCR). These assays were in
      the vast majority directed against tissue-specific markers. PCR was shown to be
      superior to conventional techniques in detecting occult tumour cells allowing the
      identification of one malignant cell mixed with 1-10 million normal cells. In
      some tumours like melanoma and prostatic carcinoma, tissue-specific transcripts
      were detected with high specificity in the blood of patients with localised and
      advanced disease. In some reports, PCR was shown to be a strong predictor of
      poorer outcome. However, due to the many limitations of PCR (e.g false
      positives), many groups are developing new approaches for the detection of occult
      tumour cells. The most attractive technique involves immunomagnetic isolation of
      CTC and micrometastases prior to downstream analysis. The tumour-rich magnetic
      fraction can be subjected to RT-PCR, immunocytochemistry and in situ
      hybridisation. This will lead to better quantification and molecular
      characterisation of these tumour cells. In conclusion, the molecular detection
      and characterisation of occult tumour cells offer a great opportunity for better
      stratifying patients with solid tumours and for developing new prognostic markers
      and targeted therapies.

PMID- 10959055
TI  - No grip, no growth: the conceptual basis of excessive proteolysis in the
      treatment of cancer.
AB  - The formation of new bloodvessels, called angiogenesis, is critical for a tumour
      to grow beyond a few mm(3) in size. A provisional matrix promotes endothelial
      cell adhesion, migration, proliferation and survival. Synthesis and degradation
      of this matrix closely resemble processes that occur during coagulation and
      fibrinolysis. Degradation of the matrix and fibrinolysis are tightly controlled
      and balanced by stimulators and inhibitors of the plasminogen activation system.
      Here we give an overview of these processes during tumour progression. We
      postulate a novel way to inhibit angiogenesis by removal of the matrix through
      specific and localised overstimulation of the plasminogen activation system.

PMID- 10959056
TI  - Therapeutic opportunities from tumour biology in metastatic colon cancer.
AB  - Tumour metastasis is the major cause of morbidity and mortality from colorectal
      cancer. While improvements in quality of life and patient survival have been made
      over the past 10 years, the majority of patients with metastatic colorectal
      cancer will die from their disease. As knowledge of the biology of colon cancer
      and its invasion/metastasis programme evolve, this presents new therapeutic
      opportunities for pharmacological and genetic intervention. This review discusses
      the current approaches to metastatic colorectal cancer therapy, details genomic
      and biological variance between primary and metastatic tumours, and highlights
      approaches for harnessing these differences to improve therapy.

PMID- 10959057
TI  - Anti-angiogenic agents: clinical trial design and therapies in development.
AB  - Development of therapies aimed at inhibiting the growth of new blood vessels is
      among the most intensively studied approaches to the treatment of cancer.
      Deciphering the many biological processes involved in tumour angiogenesis has led
      to the development of new agents targeting either metalloproteases, angiogenic
      growth factors, endothelial cells or other components of the tumour
      neovasculature. More than 35 anti-angiogenic agents have already entered clinical
      trials in cancer patients and most of them are reviewed here. It has rapidly
      emerged from the preliminary results of these studies that the steps and
      endpoints classically adopted and used worldwide in developing new anticancer
      agents could be inappropriate to assess the efficacy of agents that do not target
      cancer cells directly. One of the major challenges for scientists and clinical
      researchers is to define new surrogate endpoints adapted to anti-angiogenic
      agents in the design of clinical trials. Once this has been achieved, the place
      of clinically active anti-angiogenic agents will need to be further refined in
      order to determine where they best fit in our current armamentarium, either as
      single agents or in combination with classical anticancer therapies. Finally, the
      use of these new agents may in the future encompass every aspect of cancer
      management, not only from palliative to curative treatment but also in the
      prevention of cancer.

PMID- 10959058
TI  - Patient selection for endovascular repair of aortoiliac aneurysms.
AB  - PURPOSE: This study was conducted to establish criteria to aid in the selection
      of patients for endovascular repair of aorto-iliac aneurysms. METHODS:
      Characterization of pertinent factors used to determine whether a patient is
      eligible to undergo stent-graft repair of an aorto-iliac aneurysm. PRINCIPAL
      FINDINGS AND CONCLUSIONS: The determinant factor that dictates whether or not one
      is eligible to undergo endovascular repair of aorto-iliac aneurysm is the
      arterial anatomy of the affected area and its surrounding vessels. Some of the
      initial limitations imposed in this technology have changed such as an acceptance
      of much shorter neck than initially conceptualized, by the use of supra-renal
      stent deployment. However, unsolved issues remain regarding the differentiation
      of thrombus and atherosclerotic plaque in the infra-renal aortic region, iliac
      artery disease, and the need to have an enhanced flexibility of the delivery
      system for proper deployment in tortuous aortic necks. The question of long-term
      device durability remains the most important issue that has to be taken into
      consideration before one chooses minimally invasive endovascular approaches.

PMID- 10959059
TI  - Endovascular grafting in patients with short proximal necks: an analysis of short
      term results.
AB  - OBJECTIVES: To evaluate the safety of endovascular graft placement in patients
      with short proximal aneurysm necks, and assess factors contributing to endoleak
      formation. METHODS: 55 patients were enrolled over a two year period from five
      centers following the placement of a Talent endograft with a suprarenal stent.
      Preoperative and 30-day post-implant CT scans were retrospectively analyzed in a
      blinded fashion by two physicians. Aortic measurements were obtained, the amount
      of thrombus was subjectively graded, and any extravasation of contrast into the
      aneurysm sac defined an endoleak. The data were analyzed using a t-test. Analyses
      compared patients with proximal necks<10mm (SN), n=13) to those with longer necks
      (LN, n=42), and then contrasted patients with endoleaks (n=12), to those without
      (n=43). RESULTS: Endoleak rates were identical in the SN and LN groups (21 and
      23%). Maximal aneurysm size was larger in the SN group (63 vs 56 mm, P<0.05).
      Endoleaks were more frequently noted in larger aneurysms (P<0.05), but not
      related to SN (P=0.6). There was no correlation between endoleaks and the amount
      of thrombus, aneurysm length, proximal neck diameter or other morphologic
      characteristics. One of 12 endoleaks resulted from a problem with proximal
      fixation, nine were due to perfusing vessels, and two were undefined. The
      proximal neck diameter increased (0.9 mm) over the 30 days (P<0.005).
      CONCLUSIONS: Short-term proximal fixation can be achieved in proximal necks
      measuring less than 10mm. The narrow margin of acceptable seal mandates careful
      follow-up. Larger aneurysms were associated with an increased incidence of
      endoleaks. SNs were associated with larger aneurysms, but not with an increased
      incidence of endoleaks. Proximal neck dilation was noted, but likely relates to
      the placement of an oversized endograft during this brief period of observation.

PMID- 10959060
TI  - Coexistent coronary and cerebrovascular disease: results of simultaneous surgical
      management in specific patient groups.
AB  - OBJECTIVE: Results of synchronous combined revascularization were examined in
      specific patient groups with coexistent coronary and cerebrovascular diseases.
      METHODS: Between 1.1.1980 and 31.12.1998, 408 patients underwent a synchronous
      combined carotid endarterectomy (CEA)+myocardial revascularization (CABG). In 259
      (63.5%) patients, carotid disease was asymptomatic. Remaining patients presented
      with a previous stroke (n=35) or a transient ischemic episode (TIA) (n=114). In
      245 (60%) patients, carotid stenosis was bilateral (Group A: bilateral > or =80%
      stenosis, Group B: contralateral occlusion, Group C: contralateral subcritical
      disease). A synchronous ipsilateral CEA+CABG was performed in all patients with
      an unilateral disease (n=163) and also in all Group B (n=33) and Group C (n=142)
      patients with bilateral disease. A simultaneous bilateral CEA+CABG was performed
      in 12 high risk Group A patients. Remaining Group A patients (n=58), initially
      underwent an ipsilateral CEA for most dominant lesion+CABG, soon followed by the
      contralateral CEA. Results were examined in above specific patient Groups.
      RESULTS: Overall combined hospital mortality from stroke+myocardial infarction
      was 2.45%. No independent predictor of stroke was identified. In general, initial
      prophylactic CEA, subdued the risk of subsequent strokes for 7-8yr. Predictors of
      a late stroke were: progression of bilateral (P=0.007) and intracranial (P=0.04)
      cerebrovascular disease. Highest risk of an early stroke was recorded in Group A
      patients. A composite high risk group of patients with multiple risk factors
      (n=155) demonstrated a higher risk of both early and late strokes, as compared to
      the remaining patients (n=253) (P<0.04). Observed risk of early and late strokes,
      in specific patient groups was lower than standard predictions. CONCLUSIONS: A
      regular use of combined approach was justified in the above patient groups.

PMID- 10959061
TI  - Redo surgery for carotid artery stenosis: when and how?
AB  - PURPOSE: We analyzed operations performed at our institution retrospectively for
      recurrent carotid artery stenosis to assess the indication for surgery. We also
      assessed the techniques used for these operations. PATIENTS AND METHODS: From
      January 1992 to December 1998 1210 carotid endarterectomies were performed. Forty
      two (3.4%) of these were for recurrent stenosis. A new vein patch was implanted
      in 27 cases, PTFE patches were used in nine cases. In six cases an interposition
      with the great saphenous vein was performed. RESULTS: The mean interval between
      primary and secondary procedure was 60. 2months (3months to 23yr). Twenty five of
      our 41 patients had had ipsilateral neurologic symptoms before redo surgery, the
      remainder were free of symptoms. The grade of stenosis was over 90% in 22 cases,
      between 75 and 90% in 11 cases and below 75% in nine cases, two cases had
      aneurysmatic lesions. None of the patients died in the 30day observation period.
      One patient had a stroke with a permanent neurological deficit. In two cases
      postoperative bleeding occurred requiring reexploration. Two patients developed
      hypoglossal neurapraxia and in four patients the recurrent laryngeal nerve was
      injured. One patient had an apneic episode in the recovery room. CONCLUSION: The
      reported incidence of recurrent carotid artery stenosis surgery ranges from 3 to
      36% and our incidence is at the lower end of this range. The surgical results of
      reoperating are acceptable with a low incidence of complications.

PMID- 10959062
TI  - Pericapillary fibrin deposits and skin hypoxia precede the changes of
      lipodermatosclerosis in limbs at increased risk of developing a venous ulcer.
AB  - This study investigated the possibility that pericapillary fibrin deposition,
      found in the calf skin of patients with venous ulceration and
      lipodermatosclerosis, might already be present in the dermis of the gaiter area
      of apparently healthy limbs before any skin changes were visible. The apparently
      healthy limbs of 19 consecutive patients with a healed venous ulcer on one leg
      and no history of ulceration or clinical evidence of lipodermatosclerosis in the
      opposite calf, were studied. Bipedal ascending phlebography and foot volume
      plethysmography were performed, and systemic fibrinolytic activity and fibrinogen
      levels were calculated. Transcutaneous oxygen measurements were expressed as a
      ratio of levels from a fixed position in the gaiter skin over a control site on
      the arm. Biopsies of a standard site in the gaiter skin and the thigh were
      assessed for the presence of laminin, fibrinogen and fibronectin using
      immunofluorescent microscopy. The extent of pericapillary fluorescence was
      expressed as a ratio of the number of capillaries with deposits divided by the
      total number of capillaries staining with laminin (fibrin and fibronectin
      scores). Pericapillary fibrin deposits were observed in the dermis in 16 of the
      biopsies of the gaiter region (median score 0.20), and in eight of the biopsies
      from the thigh (median score 0.0). This difference was highly significant
      (P<0.01, Wilcoxon signed rank test). The transcutaneous oxygen ratio correlated
      negatively with the fibrin score (Spearman rank correlation coefficient -0.62,
      P<0.01), and there was a weak negative correlation between the half volume
      refilling time on foot volume plethysmography (an indicator of venous reflux) and
      the fibrin score (Speraman rank correlation coefficient -0.47, P<0.05). No such
      correlation could be shown between the fibrin score and the indicators of calf
      pump function, the euglobulin clot lysis time or the plasma fibrinogen. The
      presence of significant numbers of pericapillary fibrin deposits within the
      dermis of the gaiter skin has been demonstrated in 84% of this cohort of 'at
      risk' limbs before there is any evidence of clinical lipodermatosclerosis.

PMID- 10959063
TI  - Lower levels of PAI-2 may contribute to impaired healing in venous ulcers - a
      preliminary study.
AB  - Plasminogen activators may potentially influence the wound healing processes of
      cell migration, matrix degradation and cellular adhesion in venous ulcers by
      their regulation of protease activity. The aim of this study was to assess the
      levels of plasminogen activators in venous ulcers and to gain preliminary data
      from healing wounds. The concentrations of u-PA, t-PA, PAI-1 and PAI-2 antigen as
      well as functional u-PA were assessed in tissue homogenates from 20 chronic
      venous ulcers, six actively healing venous ulcers and five traumatic wounds. The
      concentrations of functional u-PA, u-PA antigen and PAI-1 were significantly
      greater and PAI-2 was significantly lower in the edge and base of chronic venous
      ulcers compared to adjacent intact skin (P<0.01). Healing wounds had
      significantly higher functional u-PA at the ulcer edge and higher u-PA antigen
      concentration in intact skin (P<0.05). PAI-2 levels were significantly higher in
      the ulcer edge and base in the healing wounds than in chronic venous ulcers
      (P<0.05). These findings suggest that regulation of protease activity by u-PA and
      PAI-2 may play a role in the impaired healing of chronic venous ulcers.

PMID- 10959065
TI  - Endothelium-dependent relaxation in perforating branch of human internal mammary
      artery.
AB  - The purpose of the present study was to examine the effect of acetylcholine on
      perforating branch of the human internal mammary artery (HIMA). Acetylcholine
      (10(-9)-10(-5)M) induced concentration- and endothelium-dependent relaxation
      (pEC(50)=7.54+/-0.03, maximal response was 98+/-1.3%) of the precontracted
      arterial segments. Indomethacin, 4-aminopyridine (10(-5)M) and precontraction
      with K(+)-rich Krebs-Ringer-bicarbonate solution had no effect on acethylcholine
      induced relaxation. N(G)-monomethyl-L-arginine (L-NMMA) (10(-5)M) inhibited
      relaxation evoked by acetylcholine. Indomethacin applied together with L-NMMA
      lead to further inhibition of acethylcholine-induced relaxation. Even in the
      presence of both L-NMMA and indomethacin, 4-aminopyridine had no provoked further
      inhibition of acetylcholine-induced relaxation of perforating branch of HIMA. It
      was concluded that the acethylcholine-induced relaxation of isolated perforating
      branch of HIMA is probably mediated via endothelial production of nitric oxide.
      However, when NO-synthase is inhibited, acetylcholine-induced vasorelaxation may
      be, in part, mediated through activation of cyclooxygenase pathway and consequent
      production and release of prostacyclin or some other cyclooxygenase products.

PMID- 10959064
TI  - Impact of sequential grafting of the internal thoracic or right gastroepiploic
      arteries on multiple coronary revascularization.
AB  - OBJECTIVE: The aim of the study is to clarify the efficacy of the sequential
      anastomotic technique of the arterial conduits for multiple coronary
      revascularization. BACKGROUND: The internal thoracic artery (ITA) is now widely
      accepted as a durable conduit for myocardial revascularization. The right
      gastroepiploic artery (GEA) has been developed as a third in situ arterial graft
      with an outcome similar to that of the ITA. MATERIAL AND METHOD: One hundred and
      forty five consecutive patients (116 male, 29 female, mean age 60.4yr) who
      received sequential grafting of either the ITA or GEA or both were
      retrospectively analysed. RESULTS: Sequential anastomoses were performed in 121
      in situ left ITAs, 36 in situ GEAs and 12 composite right ITAs. No in situ right
      ITA was anastomosed sequentially. Two to six vessels (mean 3.8) were
      revascularized for each patient. Of the total 543 bypassed vessels, 432 (79.6%)
      were reconstructed with the arterial grafts. In 85 patients with quadruple bypass
      or more, the arterial grafts were able to reconstruct 266 out of 360 (74.0%)
      target vessels. Seventy one patients (49.0%) were revascularized without venous
      grafts. The arterial grafts could revascularize 293 out of 310 vessels (94.5%) in
      the LAD approximately Diagonal region, 83 out of 113 (73.4%) in the distal RCA or
      Cx region. There were no cardiac events responsible for the arterial grafts in
      the follow up period. CONCLUSION: In light of our experience, multiple
      revascularization with in situ arterial sequential grafts is feasible. Aggressive
      application of this technique provides patients requiring multiple coronary
      revascularization with favorable long-term results.

PMID- 10959066
TI  - Iaterogenic injuries during retrograde delivery of cardioplegia.
AB  - During last eight years, retrograde delivery of cardioplegia was used on a
      regular basis, utilizing a DLP INC (Grand Rapids, MI) or a Research Medical INC
      (Salt Lake City UT) delivery systems, in almost an equal number of patients. This
      method resulted in a high pressure rupture, or perforation of the coronary sinus,
      its radicals or the right ventricle (RV) in 0.06% (5/7886) of patients.
      Intraoperative diagnosis of these injuries were confirmed on abnormal
      haemodynamic tracings and trans oesophageal echocardiography (TOE), and
      appearance of cardiac contusion or leakage of cardioplegia. A low incidence of
      these iaterogenic injuries may be attributed to: (1) a regular use of this method
      and (2) use of TOE guided manipulations in select high risk and reoperative
      patients. Repair of these injuries, as described, resulted in salvage of 4/5
      (80%) patients.

PMID- 10959067
TI  - Maintenance of the long-term effectiveness of tramadol in treatment of the pain
      of diabetic neuropathy.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
      tramadol in a 6-month open extension following a 6-week double-blind randomized
      trial. RESEARCH DESIGN AND METHODS: Patients with painful diabetic neuropathy who
      completed the double-blind study were eligible for enrollment in an open
      extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self
      administered pain intensity scores (scale 0-4; none to extreme pain) and pain
      relief scores (scale -1-4; worse to complete relief) were recorded the first day
      of the open extension (last day of the double-blind phase) and at 30, 90, and 180
      days. RESULTS: A total of 117 patients (56 former tramadol and 61 former placebo)
      entered the study. On the first day of the study, patients formerly treated with
      placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs.
      1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27,
      P<0.001) than former tramadol patients. By Day 90, both groups had mean pain
      intensity scores of 1.4, which were maintained throughout the study. Mean pain
      relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the
      former placebo and former tramadol groups, respectively and were maintained for
      the duration of the study. Four patients discontinued therapy due to ineffective
      pain relief; 13 patients discontinued due to adverse events. The most common
      adverse events were constipation, nausea, and headache. CONCLUSIONS: Tramadol
      provides long-term relief of the pain of diabetic neuropathy.

PMID- 10959068
TI  - Predictors of glycemic control in children with type 1 diabetes: the importance
      of race.
AB  - Diabetes is a common cause of kidney failure and blindness among young adults,
      particularly of African-American descent. Since glycemic control is a predictor
      of diabetes complications, we evaluated the impact of multiple factors including
      a special multidisciplinary management program on glycosylated hemoglobin in
      children with Type 1 diabetes. Data was collected from pediatric diabetes clinics
      in New Orleans, LA and Baltimore, MD. In New Orleans, hemoglobin A(1c) was higher
      in African-American patients 12. 5+/-3.3% (n=71) vs. 10.7+/-2.1% (n=80) in
      Caucasian children, p<0. 0001. Longer duration of diabetes was also associated
      with higher hemoglobin A(1c) in both races. The effect of race on hemoglobin
      A(1c) was independent of the influence of sex, insurance status, body mass index
      (BMI) z-score, and number of clinic visits. Covariate analysis with mean blood
      glucose levels indicated that higher hemoglobin A(1c) was attributable to higher
      mean blood glucose levels in African-American children. From the Baltimore data,
      a multidisciplinary intervention program led to improved total glycosylated
      hemoglobin for Caucasian patients but not for African-American children. Poorer
      glycemic control of African-American children is likely to predispose them to a
      higher likelihood of developing microvascular complications as they mature.
      Standard hospital-based multidisciplinary programming for diabetes management may
      have limited effectiveness in improving glycemic control of African-American
      children with diabetes. Innovative intervention programs are needed for these
      high-risk patients.

PMID- 10959069
TI  - Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in a rural
      area of Japan. The Funagata diabetes study.
AB  - PURPOSE: To determine the prevalence of type 2 diabetes and impaired sucrose
      tolerance (IGT) among people aged 40 and over in a rural area, Funagata, Japan,
      by using a 75-g oral glucose tolerance test (OGTT), and to compare the prevalence
      to that obtained from a more urban area, Hisayama, Japan. METHODS AND RESULTS:
      Total eligible subjects for the Funagata study were 3526. Among them, 140 were
      confirmed to have diabetes judged by the 1985 WHO criteria. A 75-g OGTT was
      conducted, excluding the 140 known cases of diabetes. The 1985 WHO criteria were
      used to classify the current diabetes status of participants. The overall
      participation rate was 74.4%. The prevalence of diabetes (known and newly
      diagnosed cases combined) was 9.1% for men and 10.8% for women. The prevalence of
      IGT was 12. 0% for men and 16.5% for women. Age-adjusted prevalence (using 1990
      Japanese census) of diabetes and IGT in men in Hisayama is two times higher than
      in Funagata (12.8% vs. 6.8% for diabetes, 19.5% vs. 10. 3% for IGT). Age-adjusted
      prevalence of IGT in women in Hisayama is significantly higher than in Funagata.
      CONCLUSIONS: The prevalence of type 2 diabetes among people aged 40 and over is
      approximately 10% even in a rural area of Japan. Prevalence of diabetes and IGT
      is much higher in an urban area than in a rural area in Japan.

PMID- 10959070
TI  - Prognostic indices for intra-hospital mortality in Nigerian diabetic NIDDM
      patients. Role of gender and hypertension.
AB  - Hypertension and diabetes mellitus are independently associated with a high rate
      of target organ complications, which is particularly accentuated in the Negroid
      race. The aims of this study were to evaluate the mortality associated with
      diabetes mellitus and concurrent hypertension and diabetes mellitus in indigenous
      Africans, and to identify and assess the factors that are predictive of intra
      hospital mortality in Non-Insulin Dependent Diabetes Mellitus (NIDDM) diabetic
      Nigerians. The subsequent impact of the modification of these risk factors was
      also evaluated. A prospective study of 51 hypertensive-diabetic (Non-Insulin
      Dependent Diabetics, NIDDM) Nigerians (32 males, 19 females) over a 15-month
      period, from 1996 to 1997 was undertaken. The mean admission blood pressures were
      170/102+/-35/22 mm Hg, with a body mass index (BMI) of 25.4+/-10.2 kg/m(2). A
      total of 54 normotensive (BP<130/85 mm Hg)-NIDDM diabetic Nigerians (30 men, 24
      women), who were concurrently admitted in the hospital, were compared to the
      hypertensive-NIDDM. The total mortality of all the NIDDM diabetics, as well as
      the mortality rates in normotensives and hypertensive-diabetics, were computed.
      The causes of death and associated complications were noted. Predictive indices
      of intrahospital mortality were statistically evaluated by comparison of
      proportions, chi(2) test, Fischer's exact test, logistic regression, and analysis
      of variance (ANOVA).Over-all mortality rate among all the diabetics (both
      normotensive and hypertensive) was 26.6% (28/105), which was significantly higher
      than the crude death rate on the Internal Medicine service of 17.8% (P=0.006) or
      the non-obstetric crude death rate in the hospital of 10.96% (P=0.001) Among the
      hypertensive-NIDDM patients (n=51) the mortality rate was 31.4% (16 deaths/51
      patients). This was slightly higher than the value of 22.2% (12 deaths/54
      patients) seen in normotensive -NIDDM patients. The mortality rate among the male
      diabetics (23/63 patients) 46.6% was significantly higher than female mortality
      rate of 11.6% (5/43). The 95% Confidence interval for the difference in mortality
      rates being 16.9% to 53.3% (P<0.0001, z=3.57). The impact of gender remained
      significant by the chi(2) test, chi(2)=7.17, P=0.007. 50% of the deaths in
      hypertensive-diabetics had associated stroke (8/16), while none of the 12 deaths
      among the normotensive-diabetics was stroke-related (P=0.008, Fisher's exact
      test). The case fatality rate for stroke in hypertensive-NIDDM men (7/7.9) was
      significantly greater than in hypertensive-NIDDM women (1.0/7) (P=0.04,by
      Fisher's exact test). Male gender, presence of Hyperosmolar Non-Ketotic Coma
      (HONK) (P<0. 05), associated stroke (P<0.01) and a Glasgow coma < or =10 (P<0.01)
      were found to be poor prognostic indices for mortality in hypertensive-NIDDM.
      Aggressive anti-platelet, (aspirin) anti-hypertensive, and strict glycemic
      control, instituted early and intensively, especially in male hypertensive-NIDDM
      Nigerians have resulted in reduction in the mortality rates from 26.6% in 1997 to
      12.6% in 1999 [P=0.05, 95% CI -26.9% to -1.3%]. The prognosis in 1999 of
      hospitalized African diabetics is still dismal. Hypertensive-NIDDM represents a
      higher risk group for intra-hospital mortality in black Africans. Male patients
      appear to have significantly (P<0.001) enhanced risk, especially with
      thrombotic/stroke-related deaths (P<0.01). However, intervention measures can
      reduce the mortality rate considerably, even in developing countries. The
      mechanisms of the apparent male mortality excess require elucidation.

PMID- 10959071
TI  - QTc interval and scintigraphically assessed myocardial perfusion in newly
      diagnosed and long-term type 1 diabetes mellitus.
AB  - In diabetes mellitus, heart rate corrected QT interval (QTc) has been suggested
      to be related to ischemic heart disease and increased risk of sudden cardiac
      death. The aim of the study was to analyze the length of QTc interval with regard
      to global and regional myocardial perfusion in type 1 diabetic patients.
      Myocardial perfusion was investigated in 20 newly diagnosed and 40 long-term type
      1 diabetic patients without clinical evidence for coronary artery disease by
      means of Tc-99-methoxyisobutylisonitrile (Tc-99m-MIBI)-scintigraphy (myocardial
      uptake (MU) score: 1-6). Five consecutive RR and QT intervals of resting
      electrocardiogram (ECG) tracing were measured and corrected for the previous
      cycle length. ECG-based cardiac autonomic neuropathy (CAN) was assessed with five
      cardiac reflex tests. Length of QTc interval was 423+/-29 ms in newly diagnosed
      and 433+/-26 ms in long-term type 1 diabetic patients. Nine (45%) newly diagnosed
      and 18 (45%) long-term diabetic patients demonstrated a prolonged QTc interval
      (>440 ms). Both newly diagnosed and long-term diabetic patients did not display
      significant global or regional myocardial perfusion defects (mean MU scores<3).
      In newly diagnosed diabetic patients, the length of QTc interval was related to
      global, posterior and septal Tc-99m-MIBI uptake (p<0.05, respectively). In long
      term diabetic patients, the length of QTc interval was associated with apical Tc
      99m-MIBI uptake (p<0.05). Two (10%) newly diagnosed and 19 (48%) long-term type 1
      diabetic patients demonstrated ECG-based CAN. In long-term type 1 diabetic
      patients, global myocardial Tc-99m-MIBI uptake did not differ significantly
      between patients with and without CAN. QTc interval was not significantly
      different between diabetic patients with and without ECG-based CAN (433+/-19 ms
      vs. 428+/-17 ms). Long-term diabetic patients, of whom 10 (25%) patients had
      microalbuminuria and seven (18%) patients had macroalbuminuria, demonstrated an
      association between QTc interval and albuminuria (p<0.05). The results somewhat
      suggest an association between QTc interval and vascular factors in type 1
      diabetes mellitus. Future investigations are required to analyze the role of QTc
      interval in the pathogenesis of abnormalities of myocardial perfusion.

PMID- 10959072
TI  - Diabetes enhances leukocyte accumulation in the coronary microcirculation early
      in reperfusion following ischemia.
AB  - BACKGROUND: Diabetic hearts are particularly vulnerable to ischemia-reperfusion
      injury. For leukocytes to participate in ischemia-reperfusion injury, they must
      first sequester in the microcirculation. The aim of this study was to determine,
      by direct observation, if early leukocyte deposition was increased in the
      diabetic coronary microcirculation early in reperfusion following myocardial
      ischemia. METHODS: Non-diabetic and streptozotocin (STZ)-induced diabetic rat
      hearts, subjected to 30 min of 37 degrees C, no-flow ischemia, were initially
      reperfused with blood containing labeled leukocytes. The deposition of
      fluorescent leukocytes in coronary capillaries and venules was directly
      visualized and recorded using intravital fluorescence microscopy. In addition,
      flow cytometry was used to measure CD11b adhesion molecule expression on
      polymorphonuclear (PMN) leukocytes from non-diabetic and STZ-diabetic rats.
      RESULTS: In the non-diabetic, control hearts, early in reperfusion, leukocytes
      trapped in coronary capillaries and adhered to the walls of post-capillary
      venules. In the diabetic hearts, leukocyte trapping in capillaries and adhesion
      to venules were both significantly increased (P<0.05). PMN CD11b expression was
      also significantly increased in the diabetic blood compared to the non-diabetic
      blood (P<0.05). CONCLUSIONS: Early in reperfusion following myocardial ischemia,
      leukocytes rapidly accumulate in greater numbers in the coronary microcirculation
      of the diabetic heart by both trapping in coronary capillaries and by adhering to
      venules. The enhanced retention of leukocytes in the diabetic coronary
      microcirculation increases the likelihood of inflammation-mediated reperfusion
      injury and may explain, in part, the poor recovery of diabetic hearts from an
      ischemic event.

PMID- 10959073
TI  - Cardiovascular risk in diabetes: a brief review.
AB  - Cardiovascular disease (CVD) is the major cause of the morbidity and mortality
      associated with diabetes in the US. A 2- to 3-fold incidence of CVD occurs in
      both type 1 and type 2 diabetic individuals over that in age- and gender-matched
      non-diabetic persons. Recent encouraging data demonstrating a decline in CVD
      mortality in the general US population do not reflect such a decline in the
      diabetic population, particularly in women. Increased risk for CVD is related to
      duration of diabetes and hyperglycemia, as well as hypertension, dyslipidemia,
      insulin resistance, gender, coagulation abnormalities, and other factors. Health
      care providers need to advocate for an uncompromising, multi-component attack on
      all modifiable risk factors for CVD, including glucose control, in the person
      with diabetes mellitus. This review focuses on known modifiable risk factors for
      CVD associated with diabetes, potential targets for primary and secondary
      prevention.

PMID- 10959074
TI  - Autoimmune hepatitis, autoimmune gastritis, and gastric carcinoid in a type 1
      diabetic patient: a case report.
AB  - The history of a 45-year-old male type 1 diabetic patient is presented. At the
      age of 29 years, he was diagnosed to have an autoimmune hepatitis with incipient
      liver cirrhosis. Five years later, a successful liver/pancreas transplantation
      was performed. Eighteen months later, however, pancreatic insufficiency occurred
      due to thrombosis of the pancreatic graft. Besides these conditions, iron
      deficiency, pernicious anemia, and autoimmune gastritis were also diagnosed.
      Serum parietal cell antibodies (PCA) and intrinsic factor antibodies (AIF) were
      positive. At 45, this patient was found to have a gastric carcinoid tumor. The
      clinical importance of PCA is discussed with regard to chronic atrophic gastritis
      and pernicious anemia, which both predispose toward gastric carcinoid tumors.
      Autoimmune type 1 diabetic patients who have a high prevalence of PCA should be
      screened for gastric autoimmune manifestations and tumors, as the history of this
      patient illustrates.

PMID- 10959075
TI  - Wnt/beta-catenin signaling.
AB  - The Wnt/Wingless signaling transduction pathway plays an important role in both
      embryonic development and tumorigenesis. beta-Catenin, a key component of the Wnt
      signaling pathway, interacts with the TCF/LEF family of transcription factors and
      activates transcription of Wnt target genes. Recent studies have revealed that a
      number of proteins such as, the tumor suppressor APC and Axin are involved in the
      regulation of the Wnt signaling pathway. Furthermore, mutations in APC or beta
      catenin have been found to be responsible for the genesis of human cancers.

PMID- 10959076
TI  - The platelet-derived growth factor beta receptor as a target of the bovine
      papillomavirus E5 protein.
AB  - The 44-amino acid E5 protein of bovine papillomavirus is a homo-dimeric,
      transmembrane protein that transforms cells by activating the platelet-derived
      growth factor ss receptor in a ligand-independent fashion. The E5 protein induces
      receptor activation by forming a stable complex with the receptor, thereby
      inducing receptor dimerization, trans-phosphorylation of tyrosine residues in the
      cytoplasmic domain of the receptor, and recruitment of cellular SH2 domain
      containing proteins into a signal transduction complex. Direct interactions
      between specific transmembrane and juxtamembrane amino acids in the E5 protein
      and the PDGF ss receptor appear to drive complex formation and dimerization of
      the receptor. Further analysis of this unique mechanism of viral transformation
      promises to yield new insight into the regulation of growth factor receptor
      activity and cellular signal transduction pathways.

PMID- 10959077
TI  - FGF signals for cell proliferation and migration through different pathways.
AB  - FGFs are pleiotropic growth factors that control cell proliferation, migration
      and differentiation. However, FGF transduction studies have so far focused
      primarily on the mitogenic effect of this growth factor family and it has been
      difficult to assess if the described intracellular signaling pathways are
      dedicated solely to cell proliferation, or whether they are equally important for
      the migratory activity often seen in responsive cells. We review here papers in
      which the migratory effects of this growth factor family were clearly
      discriminated from proliferative effects. In toto, these studies suggest that
      cells use different signaling pathways for migration, such as Src and p38 MAP
      kinase, from those for proliferation, which tend to upregulate the ERKs. Which
      signaling pathway a cell uses for proliferation or migration appears to depend on
      many factors, including the structure and the quantity of available FGF trapped
      in the basal lamina by heparan sulfate co-factors, the disposition of cognate
      high affinity receptors and the general environment of the cell. Thus the density
      of the cell population, the state of the cell cycle, the presence of other
      factors or receptors will modulate the migratory response of cells to FGF.

PMID- 10959078
TI  - NF-kappaB transcription factors: critical regulators of hematopoiesis and
      neuronal survival.
AB  - The Rel/NF-kappaB family of transcription factors has been implicated in the
      regulation of genes involved in immune and inflammatory responses, and of
      processes such as cell survival, apoptosis, development, differentiation, cell
      growth and neoplastic transformation. In this report we will summarize recent
      findings which highlight critical roles of NF-kappaB in different processes in
      hematopoietic and neuronal cells.

PMID- 10959079
TI  - Interferon-gamma and interleukin-12 pathway defects and human disease.
AB  - A genetic component to human mycobacterial disease susceptibility has long been
      postulated. Over the past five years, mutations in the interferon-gamma
      (IFNgamma) receptor, IL-12 receptor beta1 (IL-12Rbeta1), and IL-12 p40 genes have
      been recognized. These mutations are associated with heightened susceptibility to
      disease caused by intracellular pathogens including nontuberculous mycobacteria,
      vaccine-associated bacille Calmette Guerin (BCG), Salmonella species, and some
      viruses. We describe the genotype-phenotype correlations in IFNgamma receptor, IL
      12Rbeta1, and IL-12 p40 deficiency, and discuss how study of these diseases has
      enhanced knowledge of human host defense against mycobacteria and other
      intracellular pathogens.

PMID- 10959080
TI  - Heparin-binding EGF-like growth factor: a juxtacrine growth factor.
AB  - Heparin-binding EGF-like growth factor (HB-EGF), which belongs to the EGF-family
      growth factors, is synthesized as a membrane-anchored form (proHB-EGF).
      Proteolytic cleavage of proHB-EGF at the extracellular domain yields the soluble
      form of HB-EGF (sHB-EGF). ProHB-EGF is not only the precursor molecule for sHB
      EGF but also a biologically active molecule itself. Recent studies indicate that
      proHB-EGF has unique properties distinct from the soluble form. ProHB-EGF forms a
      complex with membrane proteins including a tetramembrane spanning protein: CD9,
      an adhesion molecule integrin: alpha3beta1, and heparan sulfate proteoglycans.
      The complex is localized at the cell-cell contact site, suggesting that proHB-EGF
      may function in cell-to-cell signaling by a juxtacrine mechanism. In an in vitro
      model system, proHB-EGF showed growth inhibitory activity, while sHB-EGF was
      growth stimulatory. Ectodomain shedding, conversion of the membrane-anchored form
      into the soluble form, is regulated by multiple signaling pathways. All these
      characteristics imply that proHB-EGF and sHB-EGF are used in different ways. In
      vivo functions of sHB-EGF and proHB-EGF have been largely undefined, but recent
      studies implicate them in a variety of physiological processes including
      blastocyst implantation and wound healing.

PMID- 10959081
TI  - Efficient production of protopectinases by Bacillus subtilis using medium based
      on soybean flour.
AB  - We have developed a culture system for efficient production of protopectinases
      (PPases) by Bacillus subtilis. PPase shows the pectin-releasing activity and is
      expected to be utilized in the enzymatic cotton scouring. B. subtilis IFO3134 was
      cultivated using defatted soybean flour as a main component of culture media.
      This strain produced three different types of PPases, namely, PPase-C, -N and -R
      performing endo-arabinase activity, pectate-lyase activity and pectin-lyase
      activity, respectively. The effects of alkaline solubilization and autoclave
      treatments to extract nutrients from soybean flour and initial soybean flour
      concentration (20-80g/l) on production of PPases in batch fermentation were
      investigated. Alkaline solubilization of soybean flour with NaOH remarkably
      reduced enzyme productivity. In addition, a higher initial concentration of
      soybean flour reduced the enzyme productivity of cells. The pectin-releasing
      activity was the largest and reached up to 2200-2400U/ml, when the culture medium
      containing an initial soybean flour concentration of 40g/l was autoclaved for 45
      60min without alkaline solubilization treatment.

PMID- 10959082
TI  - Energetics and carbon metabolism during growth of microalgal cells under
      photoautotrophic, mixotrophic and cyclic light-autotrophic/dark-heterotrophic
      conditions.
AB  - Chlorella pyrenoidosa was cultivated under photoautotrophic, mixotrophic and
      cyclic light-autotrophic/dark-heterotrophic conditions. The influence of light on
      the carbon and energy metabolism of microalgae was investigated by the use of
      metabolic flux analysis. The respiratory activity of microalgae in the light was
      assessed from the autotrophic flux distribution. Results showed that the
      glycolytic pathway, tricarboxylic acid cycle and mitochondrial oxidative
      phosphorylation maintained high activities during illumination, indicating little
      effect of light on these pathways, while the flux through the pentose phosphate
      pathway during illumination was very small due to the light-mediated regulation.
      The theoretical yields of biomass on ATP decreased in the following order:
      heterotrophic culture>mixotrophic culture>autotrophic culture, and a significant
      amount of the available ATP was required for maintenance processes in microalgal
      cells. The energy conversion efficiency between the supplied energy to culture,
      the absorbed energy by cells and the free energy conserved in ATP were analyzed
      for the different cultures. Analysis showed that the heterotrophic culture
      generated more ATP from the supplied energy than the autotrophic and mixotrophic
      cultures. The maximum thermodynamic efficiency of ATP production from the
      absorbed energy, which was calculated from the metabolic fluxes at zero growth
      rate, was the highest in the heterotrophic culture and as low as 16% in the
      autotrophic culture. By evaluating the energy economy through the energy
      utilization efficiency, it was found that the biomass yield on the supplied
      energy was the lowest in the autotrophic cultivation, and the cyclic culture gave
      the most efficient utilization of energy for biomass production.

PMID- 10959084
TI  - Multiple-impeller systems with a special emphasis on bioreactors: a critical
      review.
AB  - The multiple-impeller agitated systems are compared with single-impeller agitated
      systems with a special focus on its applications for bioreactors. Correlations
      reported in the literature for gas phase hold-up, mass transfer coefficient and
      power consumption under gassed and ungassed conditions are compared and
      recommendations have been made regarding their suitability for design and scale
      up of bioreactors. The multiple-impeller systems are found to be superior as
      compared to single-impeller systems in all the above mentioned aspects, except
      liquid mixing. For all kinds of reactors where the sole purpose is mass transfer,
      multiple-impeller systems are advantageous and there would be large savings on an
      industrial scale, especially for the bioreactors where the reaction periods are
      long and the power consumption cost could be a significant component to the
      overall production costs.

PMID- 10959083
TI  - Surfactant-lactoperoxidase complex catalytically active in organic media.
AB  - A surfactant-lactoperoxidase (LPO) complex catalytically active in organic
      solvents was developed by the emulsion coating method. The oxidation of 2,6
      dimethoxyphenol (2,6-DMP) was conducted by the surfactant-LPO complex in organic
      media. The LPO complex efficiently catalyzed the oxidation of 2,6-DMP in various
      organic solvents, although lyophilized LPO did not display the catalytic activity
      at all. To optimize the preparation and reaction conditions for the surfactant
      LPO complex, we examined the effects of pH value in the water pools of W/O
      emulsions, kinds of oxidants, and the nature of organic solvents on the oxidation
      reaction. Its optimum activity was obtained when the pH value of the aqueous
      enzyme solution was adjusted to ca. 8 at the preparation stage. The LPO complex
      exhibited the highest catalytic activity in chloroform when H(2)O(2) was employed
      as the oxidant. Furthermore, the storage stability of the surfactant-LPO complex
      was far better than that of the surfactant-horseradish peroxidase complex. This
      high storage stability of the LPO complex will be a benefit for industrial usage
      of peroxidases.

PMID- 10959085
TI  - Determination of the biosorption heats of heavy metal ions on Zoogloea ramigera
      and Rhizopus arrhizus.
AB  - The biosorption of Fe(III), Cr(VI), Pb(II), Cu(II) and Ni(II) ions on Zoogloea
      ramigera (activated sludge bacterium) and Rhizopus arrhizus (filamentous fungus)
      has been studied as a function of initial metal ion concentration and
      temperature. The applicability of the Langmuir model for each metal-microorganism
      system has been tested at different temperatures. The enthalpy change for the
      biosorption process has been evaluated by using the Langmuir constant b, related
      to the energy of adsorption. Thermodynamic parameters indicate the exothermic
      nature of Cu(II) and Ni(II) biosorption on both microorganisms. Fe(III), Cr(VI)
      and Pb(II) biosorption is determined to be an endothermic process since increased
      binding occurs as the temperature is increased in the range 15-45 degrees C.

PMID- 10959086
TI  - Biotechnological potential of coffee pulp and coffee husk for bioprocesses.
AB  - Advances in industrial biotechnology offer potential opportunities for economic
      utilization of agro-industrial residues such as coffee pulp and coffee husk.
      Coffee pulp or husk is a fibrous mucilagenous material (sub-product) obtained
      during the processing of coffee cherries by wet or dry process, respectively.
      Coffee pulp/husk contains some amount of caffeine and tannins, which makes it
      toxic in nature, resulting the disposal problem. However, it is rich in organic
      nature, which makes it an ideal substrate for microbial processes for the
      production of value-added products. Several solutions and alternative uses of the
      coffee pulp and husk have been attempted. These include as fertilizers, livestock
      feed, compost, etc. However, these applications utilize only a fraction of
      available quantity and are not technically very efficient. Attempts have been
      made to detoxify it for improved application as feed, and to produce several
      products such as enzymes, organic acids, flavour and aroma compounds, and
      mushrooms, etc. from coffee pulp/husk. Solid state fermentation has been mostly
      employed for bioconversion processes. Factorial design experiments offer useful
      information for the process optimization. This paper reviews the developments on
      processes and products developed for the value-addition of coffee pulp/husk
      through the biotechnological means.

PMID- 10959087
TI  - Mechanism and relevance of ploidy in neuroblastoma.
AB  - Neuroblastoma has a broad spectrum of clinical behavior, ranging from spontaneous
      regression to dissemination and fatality. The heterogeneity that has long puzzled
      many investigators has been shown by more recent studies to be closely correlated
      with various clinical and genetic factors. Tumor cell ploidy is one of the
      factors; diploid and near-triploid neuroblastomas show poor and excellent
      clinical outcomes, respectively. We offer a hypothesis that explains how the
      ploidy state of the tumor plays a fundamental role in this heterogeneity, and why
      various prognostic factors are correlated with each other. This hypothesis may be
      applicable to tumors other than neuroblastoma.

PMID- 10959088
TI  - Potential role for DNA topoisomerase II poisons in the generation of
      t(11;20)(p15;q11) translocations.
AB  - Chromosomal aberrations are frequently associated with therapy-related
      myelodysplastic syndromes and acute myelogenous leukemia (t-MDS/AML) and are
      thought to result from exposure to genotoxic drugs, including alkylating agents
      and DNA topoisomerase II poisons. The NUP98 gene on chromosome band 11p15 is
      involved in several different chromosomal aberrations that have been associated
      with t-MDS/AML. We have cloned the translocation breakpoints from two cases of t
      MDS harboring a t(11;20)(p15;q11). Sequence analysis of the breakpoints from both
      cases revealed almost perfectly balanced translocations between NUP98 and TOP1.
      There were no known recombinogenic sequences identified at or near the
      breakpoints. However, four bp microduplications present at the translocation
      crossover points suggested that these translocations may have been initiated by 4
      bp staggered double-stranded DNA breaks, which are known to be associated with
      the action of topoisomerase II. Given the history of patient exposure to
      topoisomerase II poisons, and the fact that these drugs stabilize staggered
      breaks with a 4 bp overhang, it seems possible that drug-induced topoisomerase II
      cleavage and subunit exchange was involved in these translocations. These results
      suggest that NUP98 is a recurrent target for therapy-related malignancies induced
      by multiagent chemotherapy, and suggest a role for DNA topoisomerase II poisons
      in the generation of these translocations. Published 2000 Wiley-Liss, Inc.

PMID- 10959089
TI  - A child with ALL and ETV6/AML1 fusion on a chromosome 12 due to an insertion of
      AML1 and loss of ETV6 from the homolog involved in a t(12;15)(p13;q15).
AB  - A 4-year-old boy was found to have acute lymphoblastic leukemia characterized by
      a t(12;15)(p13;q15). FISH investigation using a TEL(ETV6)/AML1 probe detected a
      fusion signal in 98% of the interphase cells. Sequential FISH on a G-banded slide
      showed a fusion signal on an apparently normal chromosome 12 and AML1 signals on
      chromosomes 21. The ETV6 was deleted from the chromosome 12 involved in the
      t(12;15). These results are best explained as an insertion of AML1 into TEL on
      one chromosome arm 12p and loss of ETV6 from the chromosome 12 involved in the
      t(12;15).

PMID- 10959090
TI  - Recurrent chromosome alterations in hepatocellular carcinoma detected by
      comparative genomic hybridization.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
      and has a very poor prognosis. Fifty primary HCC cases have been analyzed in the
      present study to explore the association between genomic alteration in primary
      HCC and clinical features. Several recurrent chromosomal abnormalities were
      identified in this study. The most frequently detected chromosomal gains involved
      chromosome arms 1q (33/50 cases, 66%), 8q (24/50 cases, 48%), and 20q (10/50
      cases, 20%). High-copy-number amplifications involving 1q (4 cases), 8q (3
      cases), and 20q (3 cases) were detected, and a minimum overlapping amplified
      region at 1q12-q22 was identified. The most frequently detected loss of
      chromosomal material involved 16q (35/50 cases, 70%), 17p (26/50 cases, 52%), 19p
      (21/50 cases, 42%), 4q (20/50 cases, 40%), 1p (18/50 cases, 36%), 8p (16/50
      cases, 32%), and 22q (14/50 cases, 28%). The associations between genomic
      alterations detected in the present study and clinical features including
      clinical stage, tumor size, HBV infection, chronic liver disease, and liver
      cirrhosis were explored. Our CGH results suggest that the gain of 20q and
      deletion of 8p are late genetic alterations in HCC, because the incidence of
      these alterations was obviously increased in the advanced clinical stages.
      Another finding showed that loss of 8p and gain of 8q and 20q are associated with
      tumor size. The recurrent gain and loss of chromosomal regions identified in this
      study provide candidate regions that may contain oncogenes or tumor suppressor
      genes respectively involved in HCC development and progression.

PMID- 10959091
TI  - Characterization of centromere alterations in liposarcomas.
AB  - Supernumerary ring and large marker chromosomes are a characteristic of atypical
      lipomas and well-differentiated liposarcomas (ALP-WDLPS) and are composed of
      amplified 12q14-15 sequences in association with variable segments from other
      chromosomes. Although stably transmitted, these chromosomes contain centromeric
      alterations, showing no detectable alpha-satellite sequences. We performed C
      banding, fluorescence in situ hybridization, and immunostaining with anti
      centromere antibodies in 8 cases of liposarcomas with supernumerary rings and
      large markers, including 5 ALP-WDLPS and 3 dedifferentiated-LPS and high-grade
      LPS. Our results with alpha-satellite probes and anti-CENPB antibodies confirm
      the lack of detectable alpha-satellite sequences in the five ALP-WDLPS
      supernumerary chromosomes, whereas centromeric activity was proved by the
      detection of kinetochores by using anti-CENPC antibodies. In contrast, the high
      grade and dedifferentiated liposarcomas showed a different pattern. In 2 cases,
      amplified chromosome 12 sequences, including amplification of alpha-satellite 12
      sequences in 1 case, were present on chromosomes with typical centromeres. In
      another case, the rings were similar to WDLPS-ALP rings, but a large marker
      contained a chromosome 5 centromere and amplified alpha-satellite sequences from
      chromosome 8. ALP-WDLPS is the first example of a tumor class for which the
      presence of stable analphoid chromosomes is a constant and specific abnormality.
      Formation of newly derived centromeres, so-called neocentromeres, could be an
      original and effective way to maintain a selective advantage in neoplastic cells
      by conferring stability to the supernumerary chromosomes of ALP-WDLPS. The
      activation of normally non-centromeric sequences might be obtained by an
      epigenetic mechanism due to the peculiar chromatin conformation of these highly
      complex chromosomes.

PMID- 10959092
TI  - Mutations associated with microsatellite unstable colorectal carcinomas exhibit
      widespread intratumoral heterogeneity.
AB  - Although microsatellite instability (MSI) has been shown to be present in 15% of
      sporadic colorectal carcinomas, the genetic events underlying the development of
      these tumors have not been well described. By investigating intratumoral
      heterogeneity, this study attempts to elucidate whether MSI-positive colorectal
      carcinomas develop as the result of a random accumulation of mutations or as an
      ordered, stepwise sequence of genetic alterations. Eighty-six regions from 16 MSI
      positive sporadic colorectal carcinomas were examined for mutations in repeat
      nucleotide sequences of the tumour suppressor genes transforming growth factor
      beta type II receptor (TGFBRII), insulin-like growth factor II receptor (IGFIIR),
      and BAX, and the mismatch repair genes MSH3 and MSH6. At least 2 and up to 5 of
      these genes were mutated in each tumour, and widespread intratumoral
      heterogeneity was observed for each gene. Regions of tumour with TGFBRII
      mutations were correlated with a poorly differentiated histology. Unlike the
      situation in microsatellite stable colorectal carcinomas, the findings of the
      present study did not suggest that a particular sequence of tumour suppressor and
      mismatch repair genes are mutated during colorectal tumorigenesis. It seems
      likely that a random accumulation of mutations, as a result of a defect in the
      mismatch repair pathway, drives tumour progression in this type of colorectal
      carcinoma.

PMID- 10959093
TI  - Human acid ceramidase is overexpressed but not mutated in prostate cancer.
AB  - The human acid ceramidase gene, that causes Farber disease, is located in 8p22, a
      region frequently altered in several cancers, including prostate cancer. Acid
      ceramidase catalyzes the hydrolysis of ceramide, a potent lipid second messenger
      molecule that promotes apoptosis and inhibits cellular proliferation. It is not
      known whether this gene, or its expression, is altered in prostate cancer. Here,
      we report the structural organization of the human gene, its expression in human
      tissues, and the identification of several single nucleotide polymorphisms. No
      cancer-related mutations were found in the gene in a panel of prostate tumor DNAs
      analyzed, but increased expression was observed in prostate tumor tissues when
      compared with matched normals. This increase was observed in all three prostate
      tumor cell lines tested (DU145, LnCAP, and PC3) when compared to a BPH (benign
      prostatic hyperplasia) cell line and 15/36 prostate tumors. These results suggest
      that acid ceramidase may play an important role in prostate carcinogenesis.

PMID- 10959094
TI  - Gene structure of the human receptor tyrosine kinase RON and mutation analysis in
      lung cancer samples.
AB  - The human RON gene (MST1R) maps to 3p21.3, a region frequently altered in lung
      cancer and other malignancies. It encodes a receptor tyrosine kinase (RTK)
      closely related to MET, whose mutations are associated with neoplasia. We
      investigated whether RON might be involved in the development or progression of
      lung cancer. We first determined the exon-intron structure of the gene by direct
      sequencing of RON cosmid DNA and PCR products containing intronic sequences, and
      then developed primers suitable for mutation analysis by the single-strand
      conformation polymorphism (SSCP) method. Twenty coding exons were characterized,
      all but the first one small (average size: 170 bp), a feature shared with other
      RTK genes. We performed SSCP analysis of RON in small and non-small cell lung
      cancer samples, upon detection of its expression in a sample of lung cancer cell
      lines. A mutation (T915C: L296P) was found in an adenocarcinoma specimen. Several
      single nucleotide polymorphisms were also found. The panel of intron-anchored
      primers developed in this work will be useful for mutation analysis of the RON
      gene in different types of human tumors.

PMID- 10959095
TI  - Interstitial deletion of 11q13 sequences in HeLa cells.
AB  - Previous cytogenetic and molecular genetic studies have shown that the HeLa
      (cervical carcinoma) cell line D98/AH-2 contains two apparently normal copies of
      chromosome 11 and additional 11q13-25 material translocated onto a chromosome 3
      marker. To determine the 11q13 breakpoint, we performed fluorescence in situ
      hybridization (FISH) using 18 different 11q13 specific BAC (bacterial artificial
      chromosome) and cosmid probes spanning a 5.6 Mb interval. Markers localized to
      the multiple endocrine neoplasia type 1 (MEN1) gene (menin) were also included in
      the analysis. The FISH study identified an interstitial deletion between markers
      D11S449 and GSTP1, an interval of 2.3 Mb, in the marker chromosome. This deletion
      did not include the MEN1 gene. Because point mutations and methylations can
      inactivate the MEN1 gene, single stranded conformational polymorphism (SSCP) and
      Northern and Western blot analyses were performed with MEN1 specific probes and
      antibody. SSCP did not reveal mutations of the MEN1 gene in HeLa or in seven
      other cervical cancer cell lines. Northern and Western blot studies revealed
      normal levels of expression of this gene in the cervical cancer cell lines as
      well as in HeLa cell derived tumorigenic hybrids. Because deletions of tumor
      suppressor genes often occur in cancer progression, we hypothesize that the
      inactivation of a tumor suppressor gene other than MEN1, localized to the 2.3 Mb
      interval on 11q13, might play a role in the abnormal growth behavior of HeLa
      cells in vitro or in vivo.

PMID- 10959096
TI  - Biallelic inactivating mutations and an occult germline mutation of PTEN in
      primary cervical carcinomas.
AB  - A tumor suppressor gene on chromosome sub-band 10q23.3, PTEN, is frequently
      mutated or deleted in a variety of human cancers. Germline mutations in PTEN,
      that encodes a dual-specificity phosphatase, have been implicated in two
      hamartoma-tumor syndromes that exhibit some clinical overlap, Cowden syndrome and
      Bannayan-Zonana syndrome. Although cervical cancer is not a known component of
      these two syndromes, loss of heterozygosity (LOH) of markers on chromosome arm
      10q is frequently observed in cervical cancers. To determine the potential role
      that PTEN mutation may play in cervical tumorigenesis, we screened 20 primary
      cervical cancers for LOH of polymorphic markers within and flanking the PTEN
      gene, and for intragenic mutations in the entire coding region and exon-intron
      boundaries of the PTEN gene. LOH was observed in 7 of 19 (36.8%) cases. Further,
      one sample may have homozygous deletion. Three (15%) intragenic mutations were
      found: two were somatic missense mutations in exon 5, that encodes the
      phosphatase motif, and an occult germline intronic sequence variant in intron 7,
      that we show to be associated with aberrant splicing. All three samples with the
      mutations also had LOH of the wild-type allele. These data indicate that
      disruption of PTEN by allelic loss or mutation may contribute to tumorigenesis in
      cervical cancers. In cervical cancer, unlike some other human primary carcinomas,
      e.g., those of the breast and thyroid, biallelic structural PTEN defects seem
      necessary for carcinogenesis. Further, one in 20 unselected cervical carcinomas
      was found to have a germline PTEN mutation; it is unclear whether the patient
      with this mutation had Cowden disease or a related syndrome.

PMID- 10959097
TI  - Simian virus-40 sequences are a negative prognostic cofactor in patients with
      malignant pleural mesothelioma.
AB  - Several biochemical and clinical factors have been shown to correlate with
      survival in human malignant pleural mesothelioma (MM). Nevertheless, average
      survival of 4 to 10 months from diagnosis is sometimes not sufficient for full
      expression of these factors. Several studies have reported SV40 sequences in MM,
      suggesting a possible pathogenic role. We investigated whether the presence of
      these sequences had any effect on MM patient survival. For this study, we used
      polymerase chain reaction and Southern blot analysis to search for and identify
      SV40 DNA in biopsy samples from 83 MM patients. These cases were divided
      according to histology: 62/83 (74. 7%) had epithelioid morphology (EMM) and 21/83
      (25.3%) had either biphasic or sarcomatous morphology (B/SMM). SV40 positivity
      was significantly associated with B/SMM growth pattern (chi-squared test = 5.03,
      P = 0.025). Kaplan-Meier univariate analysis confirmed the independent effect of
      histology on MM survival (log-rank test = 13.9, P < 0.001) and showed a trend for
      increased survival in SV40-negative patients (log-rank test = 2.83, P = 0.09).
      Most importantly, Cox's regression model showed that SV40-positive status
      affected the predictive value of histology on patient survival. In particular,
      when SV40 expression was added to the B/SMM histotype, Cox's regression model
      showed a significant increase in hazard ratio (HR) with respect to SV40-negative
      B/SMM (HR = 4.25, 95% CI = 2.00-9. 00, likelihood ratio test = 14.31, P < 0.001).
      We conclude that SV40 expression is significantly associated with B/SMM histology
      and represents an important prognostic cofactor when associated with the tumor
      subtype in MM patients.

PMID- 10959098
TI  - Sensitivity of FISH in detection of MLL translocations.
AB  - Fluorescence in situ hybridisation (FISH) detection of MLL translocations is now
      commonplace in cytogenetics laboratories. One of the most widely used probes is
      the Oncor MLL probe (Oncor, Gaithersburg, MD) that theoretically demonstrates the
      presence of an MLL rearrangement by a splitting of the FISH signal between the
      two derivative chromosomes generated by a translocation. Recently, another
      commercial probe has been made available from Vysis (Vysis, Downers Grove, IL)
      that uses a dual colour system. We examined material from 29 patients and 4 cell
      lines, all with recognised MLL translocations by G-banding, that were confirmed
      using Southern blot analysis of the MLL breakpoint cluster region. Both Oncor and
      Vysis MLL FISH probes were applied to these cases to compare their performance in
      detection of the MLL translocations. Thirty of the 33 cases demonstrated a clear
      splitting of Oncor MLL FISH signal in concordance with the Southern blot analysis
      and cytogenetics. Three cases failed to demonstrate a split MLL FISH signal.
      Therefore, we conclude that the Oncor MLL FISH probe has a 9.1% false negative
      rate, i.e., 90.9% sensitivity in detection of classic MLL translocations. Vysis
      MLL FISH detected the rearrangement in all 33 cases.

PMID- 10959099
TI  - CBFB/MYH11 fusion in a patient with AML-M4Eo and cytogenetically normal
      chromosomes 16.
AB  - We present a unique case of acute myeloid leukemia M4Eo (AML-M4Eo) with a
      CBFB/MYH11 fusion transcript and a trisomy 22, but in whom cytogenetic analyses
      did not disclose an inv(16). Fluorescence in situ hybridization (FISH) analysis
      with chromosome arm-specific painting probes as well as with the c40 and c36
      cosmids also revealed no evidence for an inv(16), whereas the application of
      locus-specific probes confirmed the presence of a masked inv(16). The results of
      our comprehensive FISH investigations indicate that the events leading to this
      masked inv(16) were complex and concurred with deletions on both the long and
      short arms. The most likely explanation for the formation of the relevant
      CBFB/MYH11 fusion is an insertion of parts of the MYH11 into the CBFB gene,
      although it is also possible that it was formed by a double inversion.

PMID- 10959100
TI  - Characterization of genomically amplified segments using PCR: optimizing relative
      PCR for reliable and simple gene expression and gene copy analyses.
AB  - Gene amplification is one of the mechanisms for oncogene activation in solid
      tumors. The size of the amplified regions may vary considerably among individual
      tumors, and more than one gene may be affected within the same amplicon. The main
      objective in analyzing genomic amplifications has therefore been to map the
      shortest region involved and to identify genes with increased expression as a
      result of the increased gene copy number. To facilitate such an analysis, we have
      developed simple polymerase chain reaction (PCR) procedures using the internal
      standards beta-actin (ACTB) and L1Hs for gene expression and gene copy number
      analyses, respectively. We used cDNA derived from pancreatic carcinoma cell
      lines, and genomic DNA extracted from the same cell lines, as templates in the
      gene expression and in the gene copy number analyses, respectively. To determine
      the optimal number of PCR cycles, dilution series of the templates were made.
      Furthermore, competing primers were used to adjust for differences in target
      sequence levels. We show that by these simple means it is possible to determine
      optimal conditions for expression analyses. In addition, the procedure was
      adapted for the analysis of gene copy number changes at the genomic level using
      L1Hs as the internal standard. This PCR method makes it possible to produce
      detailed gene copy number profiles of amplified genomic regions.

PMID- 10959101
TI  - Spatial heterogeneity of the Tucurui Reservoir (State of Para, Amazonia, Brazil)
      and the distribution of zooplanktonic species.
AB  - With the purpose of analyzing the horizontal distribution of the zooplankton
      community of the Tucurui Reservoir in the State of Para, Brazil, collections were
      made at 16 stations during August 1988. The stations cover the regions called
      Caraipe (C), Aracagi (B) and Ararao (A), and represent the different compartments
      of this ecosystem in regard to the morphometry and the presence or absence of
      "flooded forest". Our findings showed the existence of three compartments with
      different limnological characteristics determined as a function of the system's
      morphometry, a factor that may have influenced the horizontal circulation of the
      reservoir's water and, consequently, led to physical, chemical and biological
      differences at each of the sampled stations. All the stations presented physical
      and chemical stratification and layers of total anoxia or reduced concentrations
      of oxygen dissolved at depths corresponding to the limit of the euphotic zone.
      With regard to the zooplankton, a differentiated distribution that was mainly
      quantitative was found among the compartments (density of organisms and
      proportion among the species) in the case of Cladocera and Copepoda, and
      basically qualitative in the case of Rotifera. On the other hand, the greatest
      densities of organisms for all the groups were recorded at the Caraipe stations.
      As for the spatial distribution, some species were more restricted or more
      abundant at given stations. Among the Cladocera, there was a greater abundance of
      Moina minuta, Bosmina hagmani and Bosminopsis deitersi at the Aracagi stations,
      while C. cornuta intermedia, C. cornuta rigaudi and C. cornuta cornuta were more
      plentiful in the Caraipe and Diaphanosoma birgei in the Ararao. Among the
      Rotifera, Trochosphaera aequatoriales and Lecane proiecta, Ascomorpha ecaudis,
      besides Polyartha cf vulgaris were restricted, respectively, to the Caraipe,
      Aracagi and Ararao stations, while the others, such as Keratella americana and
      Collotheca sp., were more broadly distributed. As regards Copepoda Calanoida, the
      dominating species was found to be Notodiaptomus maracaibenses, followed by
      Notodiaptomus henseni and Argyrodiaptomus azevedoi. The most abundant Cyclopoda
      species was Thermocyclops minutus, although Thermocyclops decipiens, Mesocyclops
      longisetus, Mesocyclops meridianus e Metacyclops sp. were also found.

PMID- 10959102
TI  - [Larval competition in Chrysomya megacephala (F.) (Diptera: Calliphoridae):
      effects of different levels of larval aggregation on estimates of weight,
      fecundity and reproductive investment].
AB  - In insects that utilize patchy and ephemeral resources for feeding and egg
      laying, the outcome of larval competition for food resources depends on the
      amount of resources and the spatial distribution of immatures among patches of
      food. In the present study, the results of larval competition for food in
      Chrysomya megacephala, in traits such as female weight, fecundity and
      reproductive investment, were different in situations where the level of larval
      aggregation (proportion of competitors per amount of food) was the same, but with
      densities of competitors and amounts of food proportionally different. These
      results are indicative that the larval competition may depend both on the larval
      density and the amount of food, in different situations with the same proportion
      of larvae per gram of food.

PMID- 10959103
TI  - Electrofishing as a sampling technique for coastal stream fish populations and
      communities in the Southeast of Brazil.
AB  - Electrofishing adequacy was tested as a technique to obtain quantitative data of
      coastal stream fish populations and communities in the Southeast of Brazil. Seven
      field trips, between July/94 and July/95, were done in 5 localities of the
      Ubatiba fluvial system (Marica, RJ). Seventeen species, among the 22 collected,
      had their numbers estimated through the Zipping method, the model used to test
      the sampling methodology. At each field trip, three removals with electrofishing
      were done in each locality and, according to the number of obtained species at
      each locality/field trip, we analysed 315 cases. Nineteen cases, among 315,
      showed failure condition. Estimates were significant (p < 0.01) in 96% of the
      studied cases. Non-significant cases were obtained for rare species due to over
      and randomly efficient electrofishing in 63.3% and 36.4% of the cases,
      respectively. No correlation was found between catchability and the estimated
      number of individuals and/or environmental characteristics. High values for
      sampling efficiency (> 85%) were found for all estimates. An experimental
      analyses were done for one locality and, the comparison between the estimates for
      3 and 6 successive removals showed a mean error and a standard deviation of 5.5%
      and 2.1% respectively. Therefore, it can be concluded that electrofishing was an
      efficient method for quantitative data analysis of fish populations and
      communities in the Ubatiba fluvial system.

PMID- 10959104
TI  - Effect of the infestation by Lernaea cyprinacea Linnaeus, 1758 (Copepoda,
      Lernaeidae) on the leucocytes of Schizodon intermedius Garavello & Britski, 1990
      (Osteichthyes, Anostomidae).
AB  - Differential white blood cell counts from Schizodon intermedius infested by
      Lernaea cyprinacea were carried out and compared using the Wilcoxon matched pairs
      test. The observations were performed in fish infested by 16-77 adult Lernaea,
      fish with parasitic lesions but without attached crustaceans, and non parasitized
      fish (control group). The specimens of Schizodon intermedius were obtained from
      the University of Londrina fish farming facilities. The following leucocytes were
      observed: lymphocytes, neutrophils, monocytes, basophils, eosinophils and
      immature leucocytes. Intense lymphocytopenia and neutrophilia were observed in
      the infested hosts. Consistent increasing of monocyte percentage values occurred
      in the infested fish. The highest values for immature leucocytes counts were
      recorded from infested fish specimens.

PMID- 10959106
TI  - Uptake rates of nitrogen and phosphorus in the water by Eichhornia crassipes and
      Salvinia auriculata.
AB  - The main goal of this research was to survey information about the physiology of
      Eichhornia crassipes and Salvinia auriculata and their capacity to remove
      nitrogen and phosphorus from the environment, after quantifying the
      concentrations of the nitrogen (NO3-N, NH4-N and total-N) and phosphorus (PO4-P
      and total-P) compounds in the water. The macrophytes were incubated in the
      laboratory in plastic vials of approximately 1.5 litters containing a previously
      prepared solution of NH4NO3, NH4Cl and KH2PO4. Eichhornia crassipes exhibited the
      highest rates of nutrient reduction and the concentrations of NO3-N, NH4-N and
      PO4-P in the water influenced the uptake rates of nitrogen and phosphorus of the
      E. crassipes and S. auriculata. This information can help to reach adequate
      management strategies for aquatic macrophytes in order to reduce the
      eutrophication process in Imboassica lagoon.

PMID- 10959105
TI  - Reproductive behavior and seasonal occurrence of Psecas viridipurpureus
      (Salticidae, Araneae).
AB  - The reproductive behavior and the seasonal occurrence of Psecas viridipurpureus
      were studied at the Estacao Ecologica do Noroeste Paulista, a small conservation
      area in the northwest region of Sao Paulo State, Brazil (49 degrees 22'50"W and
      20 degrees 48'36"S). P. viridipurpureus occurred on "gravata", a bromeliaceous
      plant (Bromelia balansae, Bromeliaceae) which does not accumulate rain water.
      During the courtship display the couple occupied the median region of the
      "gravata" leaves, with the male always located in a higher position than the
      female. The males of P. viridipurpureus showed a complex courtship behavior,
      which included five motor patterns. The courtship and mating behavior occurred
      preponderantly during the rainy season and the juvenile recruitment between
      December and July. The retreat of P. viridipurpureus differs from the Salticidae
      pattern, since the egg sacs are covered with a plain silk cover and are not
      wrapped in cocoons.

PMID- 10959107
TI  - Conservation value of a native forest fragment in a region of extensive
      agriculture.
AB  - A survey of mammals and birds was carried out in a semi-deciduous forest fragment
      of 150 ha located in a zone of intensive agriculture in Ribeirao Preto, State of
      Sao Paulo, south-eastern Brazil. Line transect sampling was used to census
      mammals and birds during six days, totalling 27.8 km of trails and 27.8 hours of
      observation. Twenty mammal species were confirmed in the area (except bats and
      small mammals), including rare or endangered species, such as the mountain lion
      (Puma concolor), the maned wolf (Chrysocyon brachyurus), and the ocelot
      (Leopardus pardalis). The brown capuchin monkey (Cebus apella) and the black
      tufted-ear marmoset (Callithrix penicillata) were found frequently, suggesting
      high population density in the fragment. Regarding the avifauna, 49 bird species
      were recorded, most of them typical of open areas or forest edges. Some confirmed
      species, however, are becoming increasingly rare in the region, as for example
      the muscovy duck (Cairina moschata) and the toco toucan (Ramphastos toco). The
      results demonstrate that forest fragment of this size are refuges for native
      fauna in a region dominated almost exclusively by sugar-cane plantations. Besides
      faunal aspects, the conservation of these fragments is of great importance for
      the establishment of studies related to species preservation in the long term,
      including reintroduction and translocation projects, as well as studies related
      to genetic health of isolated populations.

PMID- 10959108
TI  - Ventilatory flow relative to intrabuccal and intraopercular volumes in the
      serrasalmid fish Piaractus mesopotamicus during normoxia and exposed to graded
      hypoxia.
AB  - Ventilation volume Vg - mlH2O.min-1 ), respiratory frequency (fR - breaths.min-1)
      and tidal volume (VT - mlH2O.breath-1 ) were measured in a group of Piaractus
      mesopotamicus (650.4 +/- 204.7 g; n = 10) during normoxia and in response to
      graded hypoxia. The fR was maintained constant, around 100 breaths.min-1, from
      normoxia until the O2 tension of the inspired water (PiO2) of 53 mmHg, below
      which it increased progressively, reaching maximum values (157.6 +/- 6.3
      breaths.min-1) at 10 mmHg. The VT rose from 1.8 +/- 0.1 to 6.0 +/- 0.5 and 5.7 +/
      0.4 mlH2O. breath-1 in the PiO2 of 16 and 10 mmHg, respectively. The Vg
      increased from 169.3 11.0 (normoxia) to 940.1 +/- 85.6 mlH2O. min-1 at the PiO2
      of 16 mmHg, below which it also tended to decrease. A second group of fish (29 to
      1510.0 g, n = 34) was used for the evaluation of allometric relationships
      concerning ventilation and dimensions of the buccal and opercular cavities. At
      maximum Vg, the VT corresponded to 93.2 +/- 2.4% of the buccal volume and 94.9
      2.3% of the opercular volume, suggesting that the Vg of P. mesopotamicus is
      limited by the volumes of buccal and opercular cavities in severe hypoxia.

PMID- 10959109
TI  - The reproductive strategy of Leporinus friderici (Characiformes, Anostomidae) in
      the Parana River basin: the effect of reservoirs.
AB  - The reproductive strategy of a species depends upon the interaction between
      intrinsic and extrinsic factors. Examining the population of Leporinus friderici
      in two reservoirs of the Upper Parana River basin in reference to first gonadal
      maturation and breeding season and sites, the present investigation tested
      whether the environment formed by damming promoted spatial and temporal changes
      in the reproductive strategy of this species. Analyses of sex ratios showed that
      females significantly predominated in Itaipu, while in Corumba the sexes were
      about equal with a slight predominance of males. Size-associated sexual
      dimorphism was observed, that is females dominated the longer length categories,
      and males the shorter. The minimum size at which L. friderici initiated
      reproduction varied from year to year, and was larger in the periods soon after
      formation of both reservoirs. In Itaipu, stabilization between the maximum and
      minimum lengths at first maturation was also noted after year 6 following closure
      and continuing until year 15. In general, the breeding season lasted from October
      through April, although cyclic changes in the duration and intensity of this
      season were evident. Young individuals predominated during the entire study
      period in Corumba. The formation of Itaipu Reservoir had a greater effect on the
      reproduction of L. friderici, where a gradual adaptation of the reproductive
      strategy of this species may possibly have been occurring. It is also possible
      that some of the characteristics of the Itaipu population will in the future be
      shown by the Corumba population. It was concluded that reproductive strategies
      constitute ecological adaptations that are temporally and spatially altered and
      are fitted to resource availability and environmental pressure.

PMID- 10959110
TI  - Ventilatory structures in Cryphocricos barozzii Signoret (Heteroptera,
      Naucoroidea).
AB  - Plastron and spiracular features strongly resemble those of Aphelocheirus
      aestivalis (Fab.), described by Messner et al. (1981). Plastronal foliose hairs,
      somewhat irregular shaped are regularly distributed in the plastron. Very
      numerous tiny openigs on sternites an tergites connect platronal air with a
      subcuticular air film limited internally apparently by a membrane. Aplicated,
      radial, structure at the proximal end of the tracheae, almost occluding the
      extremely fine spiracular openings, appear with lesser variations in both
      species, suggesting close relationships than accepted until now.

PMID- 10959111
TI  - Home range of a Geoffroy's marmoset group, Callithrix geoffroyi (Primates,
      Callitrichidae) in South-eastern Brazil.
AB  - The home range of one group of the Geoffroy's marmoset (Callithrix geoffroyi) was
      studied in a fragment of the Atlantic Forest in south-eastern Brazil, between
      February 1993 and January 1994. The total home range was 23.3 ha and the area
      used in the dry season was significantly larger than that of the wet season. The
      smallest distance travelled by group was 480 m/day in May and the longest was
      1,980 m/day in March, but with no significant differences between seasons. The
      total home range used for this species agrees with the ecological grouping of the
      genus Callithrix proposed by Rylands & Faria (1993) and may be associated with
      the habitat structure, the limit of the fragment and the inexistence of
      neighbouring groups.

PMID- 10959112
TI  - Relationship between dental morphology, sex, body length and age in Pontoporia
      blainvillei and Sotalia fluviatilis (Cetacea) in Northern Rio de Janeiro, Brazil.
AB  - The relationship between dental morphology, sex, body length and age of small
      cetaceans can be used to determine ontogeny, sexual dimorphism and geographical
      variation. The objective of this study was to determine the relationship between
      dental morphology, sex, body size and age. A total of 91 specimens of P.
      blainvillei and 80 specimens of S. fluviatilis accidentally captured in fisheries
      or stranded in northern Rio de Janeiro (21 masculine37'-22 masculine25'S), from
      September 1988 to November 1996 were analysed. The teeth root diameter in P.
      blainvillei was significantly different between the sex; the values for females
      were larger than males. In neither species aid we observed significant in
      variations dimension and number of teeth, thickness of dentine and cemental
      layers and in the maximum width of cement as a function of body size. Age was
      related to increases in tooth length, root and cingulum diameters, and maximum
      width of cement in individuals of P. blainvillei, and tooth and crown lengths and
      maximum width of cement in individuals of S. fluviatilis. The observation of a
      linear growth between maximum width of cement and age in both species indicates
      that the equations obtained can be used to estimate relative age in P.
      blainvillei and S. fluviatilis in northern of Rio de Janeiro.

PMID- 10959113
TI  - Entomological fauna from Reserva Biologica do Atol das Rocas, RN, Brazil: I.
      Morphospecies composition.
AB  - Atol das Rocas, the unique atoll in the South-western Atlantic, is located 144
      nautical miles (266 Km) northeast from the city of Natal, NE Brazil and 80
      nautical miles from Arquipelago de Fernando de Noronha, with geographic co
      ordinates 3 masculine51'S and 33 masculine49"W. It's of volcanic origin and
      coralline formation. The reef is ellipsoid, its largest axis (E-W) is
      approximately 3.7 km long, and the shortest (N-S) is 2.5 km. Inside the lagoon,
      there are two islands: the Ilha do Farol and Ilha do Cemiterio, which comprehend
      7.2 Km2 of emerged area. The Atol das Rocas lodges 143,000 birds, mainly by Sula
      dactilatra, S. leucogaster, Anous stolidus, A. minuta and Sterna fuscata. Due to
      their remote location, the islands remain largely undisturbed by the human
      activities. Aiming to a first characterization of the entomological diversity and
      the general trophic niches of atoll's entomofauna, three collects were made
      (1994, 1995 and 1996) utilizing several methods for a wide sample. One thousand
      six hundred and six insect specimens were collected belonging to eight orders: 1.
      Coleoptera - 333 individuals of Dermestidae (Dermestes cadaverinus);
      Tenebrionidae (Phaleria testacea and morphospecies) and Curculionidae (one
      morphospecies); 2. Dermaptera - 50 individuals of Carcinophoridae (Anisolabis
      maritima); 3. Diptera - 281 individuals of Ephydridae (Scatella sp. and Hecamede
      sp.) and Hippoboscidae (one morphospecies); 4. Hymenoptera - 45 individuals of
      Formicidae (Brachymyrmex sp.); 5. Lepidoptera - 111 individuals of
      Microlepidoptera (one morphospecies); 6. Mallophaga - 18 individuals in birds
      (two morphospecies); 7. Orthoptera - 237 individuals of Acrididae (Schistocerca
      cancellata), Tridactylidae (one morphospecies) and Blattidae (three
      morphospecies); 8. Thysanoptera -531 individuals (one morphospecies). Also were
      collected 112 individuals of Arachnida. The taxa of the Order Araneae were
      represented by the families: 1. Miturgidae (Cheiracanthium inclusum); 2.
      Salticidae (two morphospecies) and 3. Segestriidae (Ariadna sp.); 4. Theridiidae
      (Achaearanea sp. and Latrodectus geometricus). For the Order Scorpionida, only
      samples of Buthidae (Isometrus maculatus) were collected. Through field
      observations, it was concluded the most insects are detritophagous and/or
      necrophagous. It is suggested that which the dimension of ecological niches of
      the insects are a function of the droppings, trash and corpses of birds. A low
      diversity in the entomofauna of atoll, with its 25 morphospecies, was
      ascertained.

PMID- 10959114
TI  - Flight activity and colony strength in the stingless bee Melipona bicolor bicolor
      (Apidae, Meliponinae).
AB  - Flight activity of Melipona bicolor bicolor, coming from Cunha (23o05'S,
      44o55'W), Atlantic Forest, was studied in ten colonies, and in two periods: from
      July to September 1993 and from August to September 1995. The colonies were
      grouped in weak, medium and strong, according to the diameter of the combs, which
      can provide a good idea of the number of cells built. 855 observations were
      accomplished for 5 minutes, every half-hour, from 8 to 18 hours. The total number
      of bees that entered and left the hive and the number of bees that arrived with
      mud, pollen and resin, besides the number that went out with debris in that
      period were counted. It was also registered the temperature and the relative
      humidity of the air. The total external activity, as well as pollen collection,
      was maximum in the first hours of the morning, mainly in strong colonies. Weak
      colonies moved their maximum activity approximately to 12 hours. Pollen
      collection declined gradually, while mud and resin collection rose; removal of
      debris was greater in the beginning of the morning and in the end of the
      afternoon. Flight activity increased as relative humidity of the air rose, being
      optimum for strong colonies in the range between 80%-89%, and for the weakest
      colonies between 70%-79%. The minimum temperature observed for exit of the bees
      was 11oC, with optimum temperatures ranging between 17oC and 22oC. The results
      showed that the general state of the colony influences the different strategies
      of food collection and that these bees should be adapted to environments of high
      relative humidity as the Atlantic forest.

PMID- 10959115
TI  - Morphometrics and adaptatives aspects in africanized honeybees (Apis mellifera).
AB  - The introduction of the African bees (Apis mellifera scutelata) in Brazil and
      their expansion in the American Continent created the opportunity to study the
      process of species adaptation in a new environment. In that process, within intra
      specific variability, normalising selection can favour individuals that present a
      better adaptative morphology and they will constitute the most frequent type
      found in the population. To test that hypothesis morphometric analyses in samples
      of colonies of africanized bees and in samples of the populations were performed.
      The development of the colonies was also evaluated in terms of the amount of
      their brood, honey and pollen. Analysis of the data indicates that more developed
      colonies are formed by individuals closer to the population average with
      concerning morphological traits.

PMID- 10959116
TI  - Ontogenetic events in androgenesis of Brazilian barley genotypes.
AB  - This paper describes a simple procedure for obtention of barley (Hordeum vulgare
      L.) doubled haploid plants from Brazilian hybrid genotypes. Anatomical and
      histological examinations showed the reversion of barley pollen to an sporophytic
      mode of development. A sequence of mitosis led to the formation of multicellular
      pollen grains. Regeneration of plants occurred either by direct embryogenesis or
      callus formation followed by differentiation through direct embryogenesis or
      organogenesis. Plants were formed in the same medium used for induction
      dispensing an additional regeneration step. This procedure makes doubled haploid
      production simpler and faster. Plantlets were transferred to another medium for
      rooting and after that planted in pots with vermiculite and nutrient solution.

PMID- 10959117
TI  - The importance of glucose for the freezing tolerance/intolerance of the anuran
      amphibians Rana catesbeiana and Bufo paracnemis.
AB  - Several species of terrestrially hibernating frogs, turtles and insects have
      developed mechanisms, such as increased plasma glucose, anti-freeze proteins and
      antioxidant enzymes that resist to freezing, for survival at subzero
      temperatures. In the present study, we assessed the importance of glucose to
      cryoresistance of two anuran amphibians: the frog Rana catesbeiana and the toad
      Bufo paracnemis. Both animals were exposed to -2 degrees C for measurements of
      plasma glucose levels, liver and muscle glycogen content, haematocrit and red
      blood cell volume. Frogs survived cold exposure but toads did not. Blood glucose
      concentration increased from 40.35 +/- 7.25 to 131.87 +/- 20.72 mg/dl (P < 0.01)
      when the frogs were transferred from 20 to -2 degrees C. Glucose accumulation in
      response to cold exposition in the frogs was accompanied by a decrease (P < 0.05)
      in liver glycogen content from 3.94 +/- 0.42 to 1.33 +/- 0.36 mg/100 mg tissue,
      indicating that liver carbohydrate reserves were probably the primary carbon
      source of glucose synthesis whereas muscle carbohydrate seems unimportant. In the
      toads, the cold-induced hyperglycaemia was less (P < 0.05) pronounced (from 27.25
      +/- 1.14 to 73.72 +/- 13.50 mg/dl) and no significant change could be measured in
      liver or muscle glycogen. Cold exposition had no effect on the haematocrit of the
      frogs but significantly reduced (P < 0.01) the haematocrit of toads from 20.0 +/-
      2.1% to 5.8 +/- 1.7% due to a decreased red blood cell volume (from 1532 +/- 63
      to 728 +/- 87 mm3). When toads were injected with glucose, blood glucose
      increased to levels similar to those of frogs and haematocrit did not change, but
      this failed to make them cryoresistent. In conclusion, the lack of cold-induced
      glucose catabolism may not be the only mechanism responsible for the freeze
      intolerance of Bufo paracnemis, a freeze-intolerant species.

PMID- 10959118
TI  - Monochromatic and polychromatic visual backgrounds influence the response of area
      17 and 18 neurons after stimulation with stationary and moving light bars.
AB  - The role of colour vision in night-active cats has not been elucidated completely
      hitherto. In order to assess the colour sensitivity in cat cortical neurons we
      used large isoluminant computer-generated monochromatic and polychromatic
      background stimuli which were superimposed on moving and stationary (on/off)
      light bars. Background stimuli were moved at different speeds either inphase or
      antiphase. The modulatory effect of the visual noise on the neuronal bar was the
      primary objective of the study. The maximum amplitudes of some 40% of the neurons
      tested was influenced by both moving and stationary bars. About two thirds of
      amplitude-sensitive cells showed aldo altered direction selectivity. Latencies
      and field widths, on the other hand, turned out to be rather stable. The retino
      cortical conduction time was not influenced either. In conclusion, a large
      portion of cat cortical visual neurons is remarkably sensitive to the spectral
      composition of the visual noise process surrounding the stimulating light bar.

PMID- 10959119
TI  - The karyotype of the parasitoid Chelonus insularis Cresson (Hymenoptera,
      Braconidae, Cheloninae).
AB  - The karyotype of Chelonus insularis (Hymenoptera, Braconidae, Cheloninae) is
      described. The males show an haploid number of seven chromosomes and the females
      a diploid number of fourteen chromosomes, confirming haplo-diploid sex
      determination. Comparisons of these results with karyotypes of other species of
      the same family were done and a possible mechanism involved in the karyotype
      evolution of this species is discussed.

PMID- 10959120
TI  - Ontogenetic patterns and genetic variation in Anopheles (Anopheles) intermedius
      Chagas, 1908 and Anopheles (Anopheles) mattogrossensis Lutz & Neiva, 1911
      (Diptera: Culicidae) in the Brazilian amazon.
AB  - Changes in the expression of genes were observed during development in
      populations of Anopheles (Anopheles) intermedius and Anopheles (Anopheles)
      mattogrossensis. Esterase showed seven zones of activity: EST1 was present in all
      developmental stages of both species; EST2 was observed only in larvae of A.
      intermedius and larvae and pupae of A. mattogrossensis, with greater activity in
      pupae; EST3 and EST5 were present in all developmental stages, with greater
      intensity in larvae; EST4 and EST6 showed weak activity in larvae of A.
      mattogrossensis and was not found in A. intermedius. Leucine aminopeptidase
      showed four zones of activity, of which LAP1 and LAP2 were found in all stages of
      A. intermedius, with highest activity in larvae, and in larvae only of A.
      mattogrossensis. LAP3 was detected in all stages of A. mattogrossensis and in
      larvae only of A. intermedius. LAP4 was detected only in larvae and pupae of A.
      mattogrossensis, with greater intensity in pupae. alpha-Glycerophosphate
      dehydrogenase showed a single zone of activity, detected in older fourth-instar
      larvae and becoming more intense from the pupal stage onwards.

PMID- 10959121
TI  - Changes in lactate dehydrogenase and malate dehydrogenase activities during
      hypoxia and after temperature acclimation in the armored fish, Rhinelepis
      strigosa (Siluriformes, Loricariidae).
AB  - Lactate (LDH) and malate dehydrogenase (MDH) of white skeletal muscle of fishes
      acclimated to 20, 25 and 30 degrees C and thereafter submitted to hypoxia were
      studied in different substrate concentrations. Significant differences for LDH
      and MDH of white muscle enzyme activities are described here for the first time
      in Rhinelepis strigosa of fishes acclimated to 20 degrees C and submitted to
      hypoxia for six hours. LDH presented a significant decrease in enzyme affinity
      for pyruvate in acute hypoxia, for fishes acclimated to 20 degrees C and an
      increase for fishes acclimated to 30 degrees C.

PMID- 10959122
TI  - We are clickable.

PMID- 10959123
TI  - Changes in body fluid and energy compartments during prolonged hunger strike.
AB  - Prolonged total food deprivation in non-obese adults is rare, and few studies
      have documented body composition changes in this setting. In a group of eight
      hunger strikers who refused alimentation for 43 days, water and energy
      compartments were estimated, aiming to assess the impact of progressive
      starvation. Measurements included body mass index (BMI), triceps skinfold (TSF),
      arm muscle circumference (AMC), and bioimpedance (BIA) determinations of water,
      fat, lean body mass (LBM), and total resistance. Indirect calorimetry was also
      performed in one occasion. The age of the group was 43.3+/-6.2 years (seven
      males, one female). Only water, intermittent vitamins and electrolytes were
      ingested, and average weight loss reached 17.9%. On the last two days of the fast
      (43rd-44th day) rapid intravenous fluid, electrolyte, and vitamin replenishment
      were provided before proceeding with realimentation. Body fat decreased
      approximately 60% (BIA and TSF), whereas BMI reduced only 18%. Initial fat was
      estimated by BIA as 52.2+/-5.4% of body weight, and even on the 43rd day it was
      still measured as 19.7+/-3.8% of weight. TSF findings were much lower and
      commensurate with other anthropometric results. Water was comparatively low with
      high total resistance, and these findings rapidly reversed upon the intravenous
      rapid hydration. At the end of the starvation period, BMI (21.5+/-2.6 kg/m2) and
      most anthropometric determinations were still acceptable, suggesting efficient
      energy and muscle conservation. CONCLUSIONS: 1) All compartments diminished
      during fasting, but body fat was by far the most affected; 2) Total water was low
      and total body resistance comparatively elevated, but these findings rapidly
      reversed upon rehydration; 3) Exaggerated fat percentage estimates from BIA tests
      and simultaneous increase in lean body mass estimates suggested that this method
      was inappropriate for assessing energy compartments in the studied population; 4)
      Patients were not morphologically malnourished after 43 days of fasting; however,
      the prognostic impact of other impairments was not considered in this analysis.

PMID- 10959124
TI  - Assessment of medical courses in Brazil using student-completed questionnaires.
      Is it reliable?
AB  - INTRODUCTION: Debates about the quality of medical education have become more
      evident in the recent past, and as a result several different assessment methods
      have been refined for that purpose. The use of questionnaires filled out by
      medical students to assess the quality of lectures is one of the most common
      methods employed in our milieu. However, the reliability of this investigation
      method has not yet been systematically tested. The authors present the
      reliability of a specific form applied to the fourth grade medical students
      during the clinical psychiatry course. METHOD: Eighty-one fourth grade medical
      students were instructed to complete a form immediately after each clinical
      psychiatry lecture. Thirty-four students (42%) failed to turn in the forms after
      the final lecture. These students were given an identical form to assess the
      lectures in a retrospective fashion. The grades given by both groups of students
      for each performed lecture and the number of students who have graded an
      unperformed lecture were compared. Statistical significance for both groups was
      determined by means of the chi-square test (p< 0.05). RESULTS: Eighteen out of
      the 34 students who filled out the forms retrospectively (53%) rated the
      unperformed lecture, whereas only 5 out of the 47 students who filled out the
      forms during the course (11%) did so. This is statistically significant (p<
      0.05). There was no statistical difference for the grades given to the lectures
      that were actually performed. DISCUSSION: The authors concluded the low
      reliability rate of the retrospective evaluation warrant a continuous assessment
      method during the course.

PMID- 10959125
TI  - Predictive value of the ankle-brachial index in the evaluation of intermittent
      claudication.
AB  - The purpose of this study was to determine whether the ankle-brachial index (ABI)
      could be used to predict the prognosis for a patient with intermittent
      claudication (IC). We studied 611 patients prospectively during 28 months of
      follow-up. We analyzed the predictive power of using various levels of ABI - 0.30
      to 0.70 at 0.05 increments - in terms of the measure's specificity (association
      with a favorable outcome after exercise rehabilitation therapy) and sensitivity
      (association with a poor outcome after exercise rehabilitation therapy). We found
      that using an ABI of 0.30 as a cut-off value produced the lowest margin of error
      overall, but the predictive power was still low with respect to identifying the
      patients with a poor prognosis after non-aggressive therapeutic treatment.
      Further study is needed to perhaps identify a second factor that could increase
      the sensitivity of the test.

PMID- 10959126
TI  - Parasitic thyroid nodule in a patient with Hashimoto's chronic thyroiditis.
AB  - A case of parasitic thyroid nodule is presented. The patient was a non
      symptomatic 53-year-old white woman, on irregular course of L-thyroxine to treat
      hypothyroidism due to Hashimoto's thyroiditis. Without a history of thyroid
      trauma or surgery, she presented a 1.6 x 0.7 x 0.5cm right pre-laryngeal lymph
      node-like mass which, on ultrasonography, appeared distinct from the gland. TSH,
      thyroid peroxidase antibody and thyroglobulin antibody serum levels were elevated
      and T4-free level was normal. Thyroid and total body 99mTc isonitrile scintiscan
      showed a topic thyroid without radionuclide uptake in the nodule. Fine-needle
      aspiration of the nodule showed epithelial cells with nuclear atypia and
      oncocytic changes plus intense lymphoid infiltration and germinative center
      formation, simulating lymph node metastasis of papillary thyroid carcinoma.
      Conventional biopsy revealed a parasitic thyroid nodule with Hashimoto's chronic
      thyroiditis. Parasitic thyroid nodule must always be remembered so that
      unnecessary surgical assessment and undesirable sequels may be avoided.

PMID- 10959127
TI  - Laparoscopic treatment of retroperitoneal fibrosis: report of two cases and
      review of the literature.
AB  - OBJECTIVES: We present the results of treatment by laparoscopy of two patients
      with retroperitoneal fibrosis and review the literature since 1992, when the
      first case of this disease that was treated using laparoscopy was published. We
      also discuss the contemporary alternatives of clinical treatment with
      corticosteroids and tamoxifen. CASE REPORT: Two female patients, one with
      idiopathic retroperitoneal fibrosis, and other with retroperitoneal fibrosis
      associated with Riedel's thyroiditis, were treated using laparoscopic surgery.
      Both cases had bilateral pelvic ureteral obstruction and were treated using the
      same technique: transperitoneal laparoscopy, medial mobilization of both colons,
      liberation of both ureters from the fibrosis, and intraperitonealisation of the
      ureters. Double-J catheters were inserted before the operations and removed 3
      weeks after the procedures. The first patient underwent intraperitonealisation of
      both ureters in a single procedure. The other had 2 different surgical procedures
      because of technical difficulties during the first operation. Both patients were
      followed for more than 1 year and recovered completely from the renal
      insufficiency. One of them still has occasional vague lumbar pain. There were no
      abnormalities in the intravenous pyelography in either case. CONCLUSIONS:
      Surgical correction of retroperitoneal fibrosis, when indicated, should be
      attempted using laparoscopy. If possible, bilateral ureterolysis and
      intraperitonealisation of both ureters should be performed in the same operation.

PMID- 10959128
TI  - Research for nursing: whose job is it anyway?
AB  - Who is supposed to be generating the research evidence base for nursing? There is
      a clear demand for clinical practice to be evidence based, but there is no
      nationally acknowledged career structure which makes it clear whose job it is
      actually to do research for nursing. The roles and responsibilities of nurse
      teachers are confused, not only because of the recent exodus into universities
      and the consequent cultural changes, but also because of how they are funded.

PMID- 10959129
TI  - The globalization of nursing knowledge.
AB  - External influences placed upon nurses working in universities and in clinical
      practice require them to attract research funding, carry out research, generate
      new knowledge and publish in national and international journals. While there
      does not appear to be an agreed, unified body of nursing knowledge, critical and
      scholarly debate is essential to generate knowledge, but this is not an activity
      in which the majority of nurses can effectively participate. Nevertheless, nurses
      in the Western world are free to communicate their research, theories or ideas,
      essentially uncensored, to a vast invisible audience, and there is global
      dissemination through a vast array of literature and educational materials. This
      paper challenges nurses to examine the implications of globalization and suggests
      that the continuing debate on the nature of nursing knowledge should be updated
      to include consideration of both a change in philosophical stance and the far
      reaching effects of global dissemination of information.

PMID- 10959130
TI  - Quality assurance for nursing and midwifery education: an analysis of the
      approach in England.

PMID- 10959131
TI  - Research based nursing practice--an evaluation of an educational programme.
AB  - Although research based practice is being increasingly extolled by both the
      government and the profession, no clear educational strategy exists as to how
      practitioners should be supported in achieving this goal. Furthermore, the
      effectiveness of educational interventions in fostering a positive attitude to
      research, or a change towards a greater prevalence of research based practice,
      remains unknown. However, research has indicated that practitioners are
      dissatisfied with their research skills and the opportunities to enhance them.
      This paper describes a series of nine workshops on research utilization which
      were undertaken in a range of Trusts throughout England. The primary purpose of
      the workshops was to help nurses, health visitors and midwives to:The workshops
      were evaluated by two methods--a written semi-structured questionnaire and a
      qualitative study focused on three sites which used pre-workshop telephone
      interviews and post-workshop focus groups. Overall the workshops were effective
      in reducing fear and lack of understanding of research, alleviating the problem
      of jargon, and increasing the skills of critical appraisal. Although the
      participants' attitude to research was not changed by attending the workshops--it
      was positive before the workshop and remained so-several personal and
      professional benefits were accrued. The implications of this evaluation for
      practice, education, and research are discussed.

PMID- 10959132
TI  - The role of the Department of Health and other key institutions in the promotion
      of equal opportunities, multi-cultural and anti-racist issues in nurse education.
AB  - Equal opportunities, multi-cultural and anti-racist issues have been discussed in
      nurse education for at least two decades. This paper discusses the extent to
      which the Department of Health (DoH), United Kingdom Central Council (UKCC) and
      the English National Board (ENB) have developed, implemented and evaluated the
      above policies in nurse education. A brief overview of the wider roles of the key
      institutions are outlined. More specifically, some of the major health and social
      policies implemented during the last two decades are reviewed. This review
      concludes that the major policies have neglected or marginalized equal
      opportunities and multi-cultural issues. This is especially so for anti-racism.
      It argues that the ideologies which underpin social and health policies reinforce
      white superiority and that these ideologies are rooted in Britain's history of
      colonialism.

PMID- 10959133
TI  - On not being clear: a response to Burnard.

PMID- 10959134
TI  - Bending a habit: critical social theory as a framework for humanistic nursing
      education.
AB  - Nursing education is currently experiencing a transition away from a focus on
      behavioral outcomes and toward a focus which better reflects the humanistic,
      caring aspects of nursing. Nursing educational content and process must reflect
      this changing focus of healthcare, which itself is transgressing away from the
      inherent objectivism of acute care toward the more humanistic elements integral
      to community building. This paper studies this movement from behaviorism to
      humanism in nursing education and assumes its foundations in the tenets of
      critical social theory. The roots of critical social theory are examined,
      followed by an overview of the changes occurring within nursing education today.

PMID- 10959136
TI  - Developing an audit tool for health promotion learning opportunities in clinical
      placements.
AB  - Education audit has proved to be an effective way of reviewing current activities
      and learning opportunities available to health-care students during clinical
      placements. Despite the importance attributed to education audit in highlighting
      good practice, identifying where there is a need for change as well as providing
      information for future planning, there is no evidence in the literature to
      support its specific application to health-promotion learning opportunities. This
      paper describes a two-part study in which an education audit tool for use in
      evaluating health-promotion learning opportunities for students in clinical
      placements was successfully developed. This tool can be utilized by multiple
      stakeholders in a variety of clinical settings. Following a discussion of the
      background literature, the methodology (which involved the development of a
      series of dynamic relationships between researchers, commissioners and
      participants) is described. The aim of this article is to discuss the lessons
      learned from the process of developing the tool, including the problems that were
      encountered and how they were addressed. The authors conclude that their
      experiences in developing this tool can be usefully transferred to other
      educational and clinical settings.

PMID- 10959135
TI  - Supporting students' learning and professional development through the process of
      continuous assessment and mentorship.
AB  - This paper is based on the results of two studies carried out by the writer, over
      a period of 6 years (1991-1996), aimed to establish what happens in nursing
      practice in relation to assessing clinical competence of nursing students and the
      support they receive during their Nurse Education Programme. Study number one
      (1991-1995) was based upon the experiences and perceptions of 155 skilled
      practitioners and 300 students from three Colleges of Nursing and 45 interested
      practitioners, who volunteered to join the research at a later date because they
      were experienced assessors and mentors. Many themes and categories emerged. One
      in particular was that of the role of the practitioner who has been charged with
      the responsibility of assessing student performance on practice placement.
      Initial interviews with 155 practitioners of varying experience as assessors were
      used to design a questionnaire containing both context free and context specific
      items. Subsequent follow-up interviews were undertaken with both students and
      practitioners and non-participant observation of practitioners working with
      students were carried out. The majority of students accepted the dual role and at
      times, even the triple role of assessors, mentors and/or supervisors forced upon
      practitioners, provided that the practitioners assessing them were well prepared
      and 'trained' as assessors, were perceived to be 'fair', 'competent', 'skilful'
      and 'knowledgeable' (Neary 1997a). Study two (1992-1994) aimed to establish the
      process and outcomes of practitioner-teachers and mentorship in Wales, and was
      based on the data from a much extended period of semi-structured interviews with
      policy makers, managers, teachers and nurse practitioners (n = 360, 330 analyzed
      in detail) spanning 10 months, which gave an invaluable pictures of ongoing
      changes in the placement areas and the basis from which to construct a widely
      administered questionnaire (n = 1332) dealing with context-free and context
      specific factors underpinning the definition of the mentor role, selection and
      relationship with students. Similar logic lay behind the use of reflective semi
      structured diaries which asked 138 students and 133 practitioners to keep during
      practice placements. This study showed the practitioners readily adopted the term
      'mentor' to describe their role in their relationship with students in clinical
      practice. How they were selected for this role proved to be more complex (Davies
      et al. 1994). for the purpose of this paper the data from both studies is merged
      to give a stronger and more focused picture of how both students and
      practitioners perceived their roles in the assessment and support systems which
      were in action at the time of the studies.

PMID- 10959137
TI  - Teaching information literacy skills: an evaluation.
AB  - This paper describes an evaluation of a curriculum-integrated information
      literacy programme in an undergraduate nursing course. The aim of the programme
      was to provide students with an awareness of the discipline's literature and the
      skills to locate and retrieve the literature. A multidimensional process for
      determining nursing students' development was utilised in the evaluation of the
      programme. Pre- and post-programme questionnaires were distributed to a cohort of
      students who undertook the programme. A cohort of more senior students who had
      not undertaken the information literacy programme was utilised as a comparison
      group. Questionnaire results were analysed using a range of inferential
      statistics. This paper will focus on two main findings related to objective
      measures of information literacy skills. These include pre-programme/post
      programme change in student performance and differences in student performance
      between those who undertook the programme and those who did not. The programme
      demonstrated its effectiveness in developing information literacy skills, however
      the challenge remains for both academics and students to ensure that these skills
      are consolidated and extended for effective life-long learning.

PMID- 10959138
TI  - Nursing students' early exposure to clinical practice: an innovation in
      curriculum development.
AB  - This paper describes a pilot study addressing issues surrounding the balance and
      status given to both theory and practice in the foundation part of a pre
      registration programme. Contemporary thinking seems to suggest that there is a
      need to reverse recent trends which have placed an emphasis on theory. To
      facilitate this a framework for clinical learning was adapted to guide students'
      early exposure to clinical practice. The focus was to develop the students'
      observational and reflective skills whilst also providing the students with a
      frame of reference within which they could explore their theoretical studies. The
      information and experiences gained as a result of this study have led to the
      integration of an Orientation Framework to support students' early clinical
      experiences in a pre-registration programme.

PMID- 10959139
TI  - The perceptions of nurse teachers, student nurses and preceptors of the theory
      practice gap in nurse education.
AB  - The theory-practice gap has been the subject of much debate within nursing.
      Issues include: where the gap is, whether it is a positive or negative phenomenon
      and whether attempts should be made to bridge it. This paper describes a research
      study adopting an innovative approach to exploring the theory-practice gap by
      investigating it from the perspectives of three different groups: nurse teachers,
      student nurses and clinical preceptors. Combining the perceptions of these
      diverse groups has allowed a more complete picture of the theory-practice gap to
      emerge than is possible when examining it from one group's perspective alone.
      Twenty-three group interviews were conducted and content analysed to identify
      common themes. Mutual concerns were identified by all groups: shortness of
      clinical placements, sequencing of theory and practice, lack of collaboration
      between clinical areas and educational institutions and the lack of clarity
      regarding link teacher roles. All interviewees felt a theory-practice gap does
      exist, and whilst this could be viewed positively as a means of developing
      students' problem-solving skills, attempts should be made to minimize its impact.
      Ways to achieve this include: the development of an innovative curriculum
      allowing closer sequencing of theory and practice, evaluating the effect length
      of clinical placement has on knowledge and skill acquisition, improving
      collaboration between clinical areas and educational institutions and developing
      preceptors' lecturing roles.

PMID- 10959140
TI  - [Modern principles of standardization in detection of factor VIII activity in
      human plasma].
AB  - The authors propose a modified single-stage method for measuring the activity of
      factor VIII in human plasma, consisting in the utilization of modern philosophy
      of standardization of coagulological studies, accepted at the National Reference
      Institute of Great Britain. The authors draw attention to plotting the line of
      tested plasma titration, which is to be parallel to the calibration curve.

PMID- 10959141
TI  - [Diagnostic value of interleukin-6 level during the post-operative period].
AB  - IL-6, CRP, erythrocyte sedimentation rate, and leukocytes were evaluated in 82
      patients after planned surgery. In 60 patients the postoperative period was
      uneventful, while 22 developed purulent complications which eventuated in death
      in 6 cases. The authors show the diagnostic significance of evaluating IL-6 level
      for predicting the development of purulent complications during the postoperative
      period and their severity. Measurement of IL-6 is valuable for assessing the
      results of treatment of patients with bacterial shock.

PMID- 10959143
TI  - [Quality of laboratory analysis: search for reference points for evaluation
      (notes from the International Conference)].

PMID- 10959142
TI  - [Blood cells antigens and their antibodies (characteristics, methods of
      detection, significance in medicine) (Lecture)].

PMID- 10959144
TI  - [Laboratory medicine on the eve of the third millennium (review of the materials
      of the 17th International Congress IFCC-WORDLAB)].

PMID- 10959145
TI  - D-dimer assays in patients with carotid atherosclerosis in clinical practice.
AB  - BACKGROUND: Correlate D-dimer plasma values with the presence and degree of
      severity of atherosclerotic carotid lesions in consecutive outpatient and
      hospitalized patients without cardiovascular symptoms, checking to see if such
      correlation, if any, may be of help in daily clinical practice. METHODS: 113
      consecutive outpatient and hospitalized patients (M/F 69/44; mean age +/- SD 66
      +/- 11 years). EXCLUSION CRITERIA: acute arterial and venous thrombo-embolism,
      chronic venous insufficiency of lower limbs, active infections or inflammatory
      conditions, neoplasms, recent trauma or surgery. Ultrasonography of epiaortic
      vessels and quantitative assay of D-dimer using the ELFA method (Enzyme-Linked
      Fluorescent Assay) were carried out. RESULTS: The patients with carotid lesions
      at high thrombo-embolic risk had significantly higher D-dimer concentrations than
      those with normal IMT or with carotid presentation at low risk (1155 +/- 1099
      ng/ml vs 359 +/- 121 ng/ml and 638 +/- 468 ng/ml; ANOVA p < 0.001). Among the
      patients at high thrombo-embolic risk, 85% had values higher than cut-off (vs
      11.5% of patients with normal IMT and vs 45.5% of patients at low thromboembolic
      risk). CONCLUSIONS: D-dimer assay is a sound means for the study of angiology
      patients; normal D-dimer concentrations combined with modest lesions in the
      arterial wall are typical of patients at low thromboembolic risk. Monitoring this
      parameter may be useful between ultrasound tests. Significant increases over
      baseline values would prompt clinical intervention and justify additional
      diagnostic tests.

PMID- 10959146
TI  - Symptoms of chronic arterial insufficiency correlate with absolute ankle pressure
      better than with ankle: brachial index.
AB  - BACKGROUND: Doppler-based measurement of the ankle: brachial index (ABI) has long
      been regarded as the standard by which to objectively quantify the degree of
      lower extremity arterial occlusive disease, but this method fails to account for
      the contribution of systemic blood pressure to actual limb perfusion. We
      hypothesized that the absolute blood pressure would be a better predictor of the
      severity of symptoms of chronic occlusive disease than the ABI. EXPERIMENTAL
      DESIGN: retrospective comparative study. SETTING: university inpatient/outpatient
      vascular laboratory. PATIENTS: 1396 evaluable patients out of 2436 total
      consecutive patients referred with suspected lower extremity arterial occlusive
      disease. MEASURES: comparison of absolute ankle and digital pressures and ABI
      according to severity of symptoms of chronic lower extremity ischemia using three
      way analysis of variance (ANOVA), likelihood ratios, and receiver operator
      characteristic (ROC) curves. RESULTS: The symptoms of tissue ulcer/gangrene, rest
      pain, and gangrene were characterized by differences in absolute pressures in the
      great toe (47 +/- 42 mmHg vs 55 +/- 40 mmHg vs 62 +/- 33 mmHg [mean +/- SD], F =
      19.05, p < 0.001) and ankle (92 +/- 53 mmHg vs 98 +/- 44 mmHg vs 106 +/- 37 mmHg,
      F = 12.91, p < 0.001), but not by the ABI (0.71 +/- 0.33 vs 0.68 +/- 0.34 vs 0.71
      +/- 0.28, F = 1.24, p > 0.05). ROC curves confirmed absolute digital pressure
      (area under curve [AUC] = 0.628) and absolute ankle pressure (AUC = 0.607) to be
      superior to ABI (AUC = 0.572). CONCLUSIONS: The severity of symptoms for
      peripheral vascular disease correlate better with absolute pressure measurement
      than with ABI.

PMID- 10959147
TI  - [Thromboembolectomy with a Fogarty catheter. Our clinical experience].
AB  - BACKGROUND: The Fogarty thromboembolectomy (TE) has been considered for a long
      time the best treatment for acute peripheral arterial occlusion. However,
      recently new therapeutic options like thrombolytic agents (local or systemic)
      have been introduced. METHODS: A total of 66 patients who underwent Fogarty TE
      for acute thromboembolic limb ischemia has been retrospectively studied. Patients
      with documented atherosclerotic pathology who were treated with other
      revascularization procedures were excluded. Patients were divided into four
      groups: 1) upper limb embolism, 2) lower limb embolism, 3) thrombosis on
      atherosclerotic plaque or on a graft, 4) post-traumatic thrombosis. Twelve
      patients underwent Fogarty TE for upper limb thromboembolic ischemia and 54 for
      lower limb; 57.5% of patients had atrial fibrillation. RESULTS: Procedures were
      successful in 59 patients (89.4%). Further surgical procedures (bypass,
      arterioplasty, further embolectomy) were performed in 35.1% (19/54) of patients
      of groups 2 and 3 with acute lower limb ischemia. Results were very good in group
      1 and 4. Seven of the 54 patients treated for lower limb ischemia underwent limb
      amputation (12.9%), while hospital mortality was similar for lower and upper limb
      (31.4 and 33.3% respectively). CONCLUSIONS: The Fogarty TE is still a good option
      to revascularize acute ischemic peripheral arteries with good results in a high
      number of patients and should be particularly used where it is possible to
      perform additional techniques in case of failure.

PMID- 10959148
TI  - Thrombosis and cancer.
AB  - Although the association between malignant disease and thrombosis was first
      recognised by Trousseau in 1865, many aspects of this complex relationship are
      still obscure. Cancer patients have an increased risk of developing thrombosis.
      Similarly, patients presenting with idiopathic venous thromboembolism are
      considered to have a higher risk of developing cancer. However, no data exist
      that warrant thorough screening for cancer in these patients--apart from history
      taking, physical examination, routine investigations, and chest X-ray. Tumour
      cells activate the blood coagulation system either by directly stimulating
      thrombin formation or by inducing mononuclear cells to synthesise procoagulants.
      Both cancer cells and chemotherapeutic agents damage the endothelium by further
      enhancing the hypercoagulable state of malignancy. With few exceptions, the
      diagnosis and treatment of thrombosis in cancer patients are the same as in
      patients without cancer. Cancer patients are considered eligible for primary
      prevention of venous thromboembolism when they are receiving chemotherapy, if
      they have indwelling central venous catheters, when they are immobilised and,
      more importantly, when they undergo surgery. Secondary prevention in recurrent
      venous thrombosis may require the administration of oral anticoagulants or, in
      cases of resistance to warfarin, adjusted doses of heparin.

PMID- 10959150
TI  - Considerations on pulsoplethysmographic changes in fingers due to iontophoresis
      with methacholine in subjects with Raynaud's phenomenon.
AB  - This paper presents a study of plethysmographic changes induced by methacholine
      (a derivative of acetylcholine) administered via iontophoresis in a population of
      41 young women with apparently primary Raynaud's disease. All patients presented
      with a very clear statistically significant sphygmic increment, obviously
      connected with the vasodilatation caused by methacholine. Moreover, in nearly
      half of the 23 cases whose reaction to passive postural variations was
      successively examined by plethysmography, the district circulatory response was
      characterised by persistent neurogenous vasoconstriction due to methacholine or
      by inadequate vasomotor EDRF mediated modulation. The authors believe that their
      findings serve as further evidence of the pathogenetic mechanisms of Raynaud's
      disease. This is because they highlight the role played by "balance of vessel
      motility" which would guarantee district circulatory homeostasis. Concrete proof
      thus corroborates well known indirect evidence that a pathological vasospasm can
      be triggered and persist when two fundamental conditions are met: a) intense
      vasoconstriction initially of neurological origin and successively reinforced by
      biohumoural synergic stimuli; b) the breakdown of the capacity for EDRF mediated
      intrinsic vasomotor modulation. It is suggested that the prevalence of one or the
      other factor would lead to a variety of clinical pictures denoting vascular
      acrosyndromes of this type. The ability to single out such clinical pictures by
      adding the iontophoresis test with methacholine to routine screening procedures
      for the presence of Raynaud's disease, would allow physicians to make more
      accurate diagnosis and improve therapy.

PMID- 10959151
TI  - [How dangerous is Candida in the intestine? The great fungal business].

PMID- 10959152
TI  - [Enzymes for gonarthrosis. As effective as NSAID, or not?].

PMID- 10959149
TI  - Two incidental cases of abdominal aortic aneurysm and gallbladder cancer. Further
      data influencing the management of patients affected by aneurysm and gallbladder
      disease.
AB  - Abdominal aortic aneurysm and cholelithiasis are two common diseases in the
      elderly population. The prevalence of abdominal aortic aneurysms ranges between
      1.8 and 6.6% in autoptic series and it's estimated that 2.5% of the over sixty
      year old population is affected. Carcinoma of the gallbladder is the most common
      malignant tumor of the biliary tract and in the United States is the fifth most
      frequent digestive tract malignancy; it's incidence ranges between 2 to 10 cases
      of 100,000 persons/year. No adequate guidelines are now available to assist the
      surgeon, in the case of concomitant gallbladder disease and abdominal aortic
      aneurysm. In this paper the management of abdominal aortic aneurysm in a patient
      with gallbladder disease is discussed in order to assist the surgeon deciding
      whether to perform concomitant aneurysm resection and cholecystectomy. In 162
      aneurysmectomies (1987-1997) 18 (11.11%) patients underwent combined
      aneurysmectomy and cholecystectomy operation. The patients ranged in age from 49
      to 88 years (average 69 years). In two cases the anatomo-histological specimen
      examinations (twelve sections) demonstrated a gallbladder carcinoma. The overall
      mortality rate was 5.56% either for aneurysmectomy alone or for combined therapy.
      In case of abdominal aortic aneurysm and concomitant gallbladder disease, in
      choosing simple endoaneurysmectomy, the surgeon has to consider the risk of early
      and late complications of leaving a diseased gallbladder in place. In case of
      concomitant performance of both operations, the risks of a possible septic graft
      contamination must be considered. We believe that the patient may be best served
      by performing the vascular and nonvascular procedures in the same operation. In
      this paper a new proof, till now never considered in the international
      literature, is presented to support our opinion: the possibility of concomitant
      unknown cancer or precancerous lesions in a lithiasic gallbladder. Diagnosis of
      these lesions is, indeed, not easy to perform in the preoperative phase and is
      often a postoperative anatomo-histological detection.

PMID- 10959153
TI  - [High-tech endoscopy with color injection. Colors for the intestine].

PMID- 10959154
TI  - [When sweating impairs life style. How your patients can become "dry". Interview
      by Petra Eiden].

PMID- 10959155
TI  - [New trends in therapy of diabetes. More freedom, fewer risks, comfortable
      insulin administration].
AB  - The incidence of diabetes mellitus is increasing worldwide. Strict metabolic
      control can prevent late sequelae of this disease. For this purpose, not only
      more potent drugs with fewer side effects are needed, but also user-friendly
      techniques and devices for self-monitoring of blood glucose and the less painful
      application of insulin (jet application, inhalable insulin). More user-friendly
      insulins are the rapid- and short-acting human insulin analogues, which do away
      with the bothersome injection/meal interval, and improve the postprandial
      glycemic response. New long-acting insulins reduce the frequency of injections
      and the occurrence of nocturnal hypoglycemia. Type 2 diabetics will presumable
      benefit from the use of the rapid, short-acting glinides, for example, by
      enabling a greater measure of eating freedom during the course of the day. The
      thiazolidinediones, a group of agents that enhance the effects of insulin in
      target tissue, reduce insulin resistance and improve insulin sensitivity.

PMID- 10959156
TI  - [Diabetes therapy related to etiology. Indications, uses and side effects of new
      insulin sensitizers].
AB  - Via their central point of attack on the nuclear PPAR gamma receptors,
      thiazolidinediones improve insulin sensitivity and thus bring lower blood sugar
      and insulin levels. Depending on the group of patients investigated, they reduce
      the HbA1c by 0.7% to 1.5%. Rosiglitazone and pioglitazone will soon be available
      on the European market. In contrast to troglitazone they show no signs of any
      hepatotoxic effect in the studies performed to date. Common to the class of
      insulin sensitizers is their effect in promoting the differentiation of
      subcutaneous adipocytes, leading to subsequent weight increase and the
      development of edema.

PMID- 10959157
TI  - [Antidiabetic drug at every meal. Repaglinide is especially recommended for
      slender type 2 diabetic patients].
AB  - Repaglinide is the first stimulator of insulin secretion from the new meglitinide
      family. Via specific binding to the ATP-sensitive potassium channel of the beta
      cell membrane, it stimulates the rapid release of insulin. In preclinical
      studies, the insulin-stimulating effect of repaglinide has been found to be 10 to
      20 times more potent than that of glibenclamide. Repaglinide is rapidly absorbed
      and has a short action, which makes it particularly well suited for the
      regulation of prandial blood glucose and meal-related dose adjustment. Since
      repaglinide is eliminated almost exclusively by non-renal routes, it can be used
      without danger in patients with moderately reduced renal function. Repaglinide is
      a suitable agent for first-line monotherapy in patients whose glucose metabolism
      cannot be optimally controlled by increasing physical activity and appropriate
      dietary measures. Repaglinide is clearly superior to glibenclamide in reducing
      postprandial hyperglycemia, and has a lower hypoglycemia risk than all the
      sulphonylureas. The flexibility of repaglinide makes it possible for good oral
      meal-related treatment.

PMID- 10959158
TI  - [Small dosage--strong effect. Complementary medicine, 3: Homeopathy].

PMID- 10959159
TI  - [Progress in environmental medicine. Biocides, molds and amalgam are the most
      frequent environmental toxins].

PMID- 10959160
TI  - [PHARAO Study of the Hypertension League. Can development of hypertension be
      prevented with drugs?].

PMID- 10959161
TI  - [Ambulatory detoxification of alcoholic patients. Results of a model project].
AB  - At present, institutions in Germany that concern themselves with the
      detoxification of alcoholics on an outpatient basis are few and far between,
      despite the fact that such an approach is quite common in other countries such as
      the USA. Problems are associated both with the careful diagnostic work-up of the
      patient aimed at assessing possible risks, and with the pharmacotherapy that
      might be needed. The present article describes a model project, which was
      initiated in 1998 under the scientific and clinical supervision of the Department
      of Psychiatry of the University Hospital in Munich. The concept behind the
      project and the clinical results achieved with the first 47 detoxified patients
      are presented and discussed.

PMID- 10959162
TI  - [Natural latex allergy. Symptoms, risk groups, prevention].

PMID- 10959163
TI  - [Diagnostic quiz. Skin eruptions and memory loss. Eruptive xanthomas].

PMID- 10959164
TI  - [Controversial judgment in the Dortmund federal court. Is patient education
      superfluous when everything is written down in the package insert?].

PMID- 10959165
TI  - [More protection for the kidneys of diabetic patients. PROSIT Project shows
      initial success].

PMID- 10959166
TI  - [Statins inhibit inflammatory reaction. CRP advances as a marker of coronary
      risk].

PMID- 10959168
TI  - [A new combined vaccine. 6 at once].

PMID- 10959167
TI  - [Alcoholism. No organ remains free of damage].

PMID- 10959169
TI  - [Lispro mixed insulins in type 2 diabetes. Preventing postprandial insulin rise].

PMID- 10959170
TI  - [Pharmaceutical industry makes a declaration. Genes can be safely used for
      patients].

PMID- 10959171
TI  - The AMA to Gov. Whitman: Aetna US Healthcare causing serious concerns.

PMID- 10959172
TI  - Patrick J. Zenner.

PMID- 10959173
TI  - Legislative process thoroughly tested in HMO repayment plan.

PMID- 10959174
TI  - The diabetes and obesity epidemic among the Pima Indians.
AB  - The Pima Indians are the fattest population group in the fattest country on
      earth, and they have the highest prevalence of diabetes in the world. Despite
      unprecedented research by the National Institute of Arthritis, Diabetes and
      Digestive and Kidney Diseases (NIH) and good care by the Indian Health Service
      (IHS), the problems have grown worse since first recognized in 1963. The causes
      are multiple: environmental, genetic, cultural, and psychosocial. The real
      villian, however, is the disease, diabetes. The solution is prevention in Pima
      children.

PMID- 10959175
TI  - The New Jersey Youth Tobacco Survey: implications for policies, programs, and
      clinical practice.

PMID- 10959176
TI  - The economic impact of the pharmaceutical and medical technology industry in New
      Jersey.

PMID- 10959178
TI  - Selman A. Waksman, the Garden State, and the antibiotic revolution.

PMID- 10959177
TI  - Web-based technology: what every physician practice needs to know.

PMID- 10959179
TI  - Humanism marks Academy of Medicine's awards.

PMID- 10959180
TI  - [Hyperbaric oxygen therapy in retinal artery occlusion].
AB  - Retinal artery occlusion (RAO) is an ophthalmological emergency that causes a
      major decrease of visual parameters in most of the cases. Purpose of this pilot
      study was to evaluate the effect of adjunctive hyperbaric oxygen therapy (HBO) on
      visual acuity (VA). PATIENTS AND METHODS: Patients with acute central or branch
      artery occlusion (CRAO/BRAO) consecutively admitted to our hospital were offered
      adjunctive HBO. Standard therapy consisted of ocular massage for 3 minutes,
      paracentesis and intravenous acetazolamide. HBO (3 x 30 minutes at 240 kPa) was
      applied t.i.d. on the first day, b.i.d. on day 2 and 3 and o.d. for at least
      another 4 days. Patients who refused HBO or had contraindications served as
      controls. VA was measured according to the guidelines of ETDRS. The follow up was
      3 months. RESULTS: HBO: 8 patients with CRAO showed a mean increase in VA of 1
      line, 4 of 8 patients had an increase of 2 lines and more, in 3 of 8 patients VA
      was unchanged and one patient suffered a decrease of 6 lines. 10 patients with
      BRAO showed a mean increase in VA of 8 lines, 8 of 10 patients showed an mean
      increase of 2 and more lines, in 2 of 10 patients VA was unchanged. CONTROLS: 8
      Patients with CRAO had a mean increase of 2 lines during follow up, 3 of 8
      patients showed an increase of 2 lines and more, in 5 of 8 patients VA was
      unchanged. 6 patients with BRAO had a mean increase of VA of 4 lines, 3 of 6
      patients had an increase of 2 lines and more, one patient lost 3 lines and in 2
      patients VA was unchanged. The results are compared to the literature.
      CONCLUSIONS: HBO seems to be beneficial for VA in eyes with BRAO. Further
      investigations are necessary to prove this observation.

PMID- 10959181
TI  - [Effects of carotid artery thrombendarterectomy on pulsatile ocular blood flow].
AB  - Successful operations of clinically significant carotid artery stenosis by
      carotid endarterectomy (CEA) are leading to a better perfusion in the region of
      this artery. It still creates problems to make a statement about cerebral and
      ocular perfusion during the operation. METHODS: In 10 patients who underwent a
      CEA the pulse amplitude (PA) of the intraocular pressure (IOP) was measured
      intraoperatively by a pneumotomography (OBF-Systems, U.K.) and the so called
      pulsatile ocular blood flow (pOBF) was determined. The middle arterial blood
      pressure (MAP) was taken invasively during the operation. RESULTS: During the
      clamping phases no PA could be recorded. PA (p = 0.04) and pOBF (p = 0.028)
      increased on the side which had been operated on. No correlations of PA and pOBF
      to MAP were found. CONCLUSION: This method can prove an increased pulsatile
      ocular blood flow after successful CEA.

PMID- 10959183
TI  - [Impression and applanation tonometry in irregular corneas. Comparison with
      intraocular needle tonometry].
AB  - PURPOSE: During the past 4 years we have demonstrated in eyes with corneal
      pathology that applanation tonometry (Goldmann, Perkins) generally delivers
      falsely low measurements in comparison to intraocular needle tonometry. The aim
      of this study was to evaluate whether impression tonometry (Schioetz) is more
      precise than applanation tonometry in determining the intraocular pressure in
      eyes with corneal disorders. PATIENTS AND METHODS: In 75 eyes with suspected
      glaucoma and various corneal disorders, we performed applanation tonometry and
      impression tonometry before intraocular needle tonometry. Applanation tonometry
      was repeated after impression tonometry to unveil a possible tonography effect.
      Intraocular needle tonometry was performed thereafter. RESULTS: Applanation
      tonometry results were 4.1 +/- 5.3 mmHg below intraocular pressure as determined
      by intraocular needle tonometry. Impression tonometry results were also lower:
      4.3 +/- 6.8 mmHg (5.5 g), 4.3 +/- 6.4 mmHg (7.5 g), and 4.8 +/- 7.0 mmHg (10.0
      g). The differences between applanation tonometry and impression tonometry were
      statistically not significant. In contrast, all the differences between
      extraocular tonometry procedures and intraocular needle tonometry were
      statistically highly significant (P < 0.001). CONCLUSION: In corneal pathology
      both, applanation tonometry and impression tonometry do not deliver reliable
      results on an average. Only intraocular needle-tonometry delivers reliable
      results in these eyes.

PMID- 10959182
TI  - [Intraocular pressure reduction by endoscopically controlled erbium:YAG
      goniotomy].
AB  - BACKGROUND: Microperforations of the trabecular meshwork can be made using an
      endoscope guided Er:YAG laser. As shown in enucleated human melanoma eyes, these
      microperforations are not accompanied by thermal damage of the surrounding
      tissue. We now report our first clinical results using a commercially available
      endoscope/laser system for performing this particular kind of goniotomy. PATIENTS
      AND METHOD: A combined cataract extraction and Er:YAG goniotomy was performed in
      24 eyes of 20 patients. Seventeen eyes were reexamined after a minimum follow-up
      of 4 months (mean 6.5 months, max. 12 months). The results were compared to a
      control group having only the cataract operation (14 eyes). RESULTS: After
      combined cataract operation and Er:YAG goniotomy, mean intraocular pressure
      dropped from 21.8 to 15.5 mmHg. Intraocular pressure regulation was successful in
      88% of these cases. In contrast to this, the intraocular pressure reduction in
      eyes having only the cataract operation was much less pronounced (mean
      intraocular pressure preoperative 20.0, postoperative 17.4, success rate 35%).
      CONCLUSION: The first results with our particular endoscope/laser system are
      encouraging. Other groups using comparable devices have reported similar success
      rates. We hope that the endoscopic Er:YAG goniotomy may become a minimally
      invasive type of glaucoma surgery in the near future.

PMID- 10959185
TI  - [Haze and regression after photoreactive keratectomy (PRK)].
AB  - According to the recommendations of the German Ophthalmological Society (DOG),
      PRK in myopic patients between -1.0 dpt and -6.0 dpt is a scientific acknowledge
      treatment. The risks of the treatment, however, increase in myopia above -6.0
      dpt. MATERIAL AND METHODS: Between june 1994 and october 1997 we performed PRK on
      338 eyes from 212 myopic patients in the ALZ Eye Clinic Hamburg. Myopia ranged
      between -1.25 and -11.25 diopters. All treatments were performed with the Keracor
      116 (Fa. Chiron Technolas). The procedure was the same in all cases: mechanical
      abrasion, excimer laser treatment, antibiotic and nonsteroidal antiphlogistic
      drops for three days followed by a corticosteroid therapy for 5 months. RESULTS:
      Out of these 338 eyes, 17 eyes after 12 months had a persistent haze grade 1-2 or
      more according to Stein, Cheskes and Stein. These 17 eyes had also an average
      regression of -1.67 diopters (SD 1.8) and lost at least in minimum two lines of
      the best corrected visual acuity 12 months postoperatively. The refraction of the
      17 eyes was more than -6 dpt preoperatively. CONCLUSION: Haze after PRK is in
      most cases only transient. Haze of grade 1-2 or more after 12 months
      postoperatively is correlated with regression and a loss of best corrected visual
      acuity. PRK below -6 dpt in our hands never showed haze grade 1-2 or more 12
      months postoperatively. Therefore patients with a refraction of more than -6 dpt
      before PRK should be informed about this potential risks. In these cases LASIK
      should be taken into consideration.

PMID- 10959184
TI  - [Vitreoretinal surgery in complicated retinal detachment in children and
      adolescents].
AB  - BACKGROUND: The purpose of this study was to evaluate anatomical and functional
      results of vitreoretinal silicone oil surgery for complicated retinal detachments
      due to trauma and myopia in children and juveniles. METHODS: We retrospectively
      reviewed the records of children and juveniles up to 17 years of age who had
      undergone vitreoretinal surgery with silicone oil instillation for the above
      causes between 1990 and 1997. A total of 30 eyes of 29 patients were operated on,
      24 because of trauma and the remaining 6 because of retinal detachment in high
      myopia. There was a mean postoperative follow-up period of 1.7 years. Silicone
      oil could be removed from 18 of the 30 eyes after a mean of 4.7 months. The
      median number of vitrectomies performed per eye was two (range one to five).
      RESULTS: In 21 of 30 eyes (70%) the retina could be reattached after one or more
      surgeries. Silicone oil was removed from 16 of these 21 eyes (53%) which was
      defined as anatomical success. Visual acuity increased (14 eyes, 48.3%) or
      remained unchanged (9 eyes, 31%) in 23 of 29 eyes (79.3%). Visual acuity
      decreased in 6 of 29 eyes (20.7%) despite surgery. Two eyes (6.7%) had to be
      enucleated due to bulbar phthisis. Seventeen eyes reached a postoperative visual
      acuity of at least counting fingers. In one child functional tests could not be
      performed due to young age. CONCLUSION: Vitreoretinal surgery with silicone oil
      endotamponade has become a standard procedure in treating complicated retinal
      pathologies in children and juveniles. In very young patients it is thought that
      silicone oil instillation has advantages over gas endotamponade since it is very
      difficult for children to keep the proper face-down positioning after the
      procedure. The retinal reattachment rate is encouraging. In the majority of cases
      visual acuity greater than or equal to counting fingers and thus orienting vision
      was reached postoperatively. In few cases even reading vision was regained.

PMID- 10959186
TI  - [Perimetry findings and driving performance. "How much visual field" does a
      motorist need?].
AB  - OBJECTIVE: On 01-01-99 the new driving licence regulations came into force. Are
      the visual field criteria mentioned there sufficient for an adequate evaluation
      of driving fitness? METHODS: Typical (binocular) visual field defects were
      digitally superimposed onto photographs of traffic scenes to show the influence
      of such scotomata on visual perception. RESULTS: Exemplary cases clearly show
      that evaluation of visual field borders alone is not sufficient for evaluating
      driving fitness. They also prove that binocular scotomata affecting the (para
      )central region of the visual field are of special importance to driving
      performance. The actual guidelines given by the traffic commission of the German
      Ophthalmological Society (DOG) and the legally defined limits will be critically
      discussed. CONCLUSION: From the ophthalmological point of view the actual visual
      field criteria of the new driving licence regulations do not seem to be
      sufficient for the evaluation of driving fitness: An additional consideration of
      (para-)central scotoma is mandatory. This publication provides recommendations
      for execution and interpretation of perimetric examinations for traffic
      ophthalmological purposes.

PMID- 10959188
TI  - [Internet presence and home page design for the ophthalmologist].
AB  - An increasing number of people uses the internet for information retrieval. In
      the past three years nearly every University Eye Hospital provides its own
      information using homepages in the Internet. More and more Eye Departments and
      comprehensive ophthalmologists use the Internet to provide information on their
      own. We provide advice for the selection of a provider, use examples on how to
      deal with an HTML editor program and explain the technical realisation of the own
      Internet presence. Legal circumstances and strategies to promote the own homepage
      are discussed.

PMID- 10959187
TI  - [Hereditary motor and sensory neuropathy type I associated with a unilateral
      incomplete external oculomotor paralysis. A case report].
AB  - HMSN is a hereditary symmetric ascending neuropathy of the peripheral nerves.
      Several cases of HMSN with motility disorders of both eyes have been reported in
      the literature. We describe a patient with HMSN type 1 and an incomplete
      peripheral 3rd nerve palsy of the right eye. To the best of our knowledge, this
      is the first report of developed unilateral oculomotor disorder in a patient with
      HMSN.

PMID- 10959190
TI  - [Silicone oils in retinal surgery ].

PMID- 10959189
TI  - [Distinct papilledema in pseudotumor cerebri in vitamin A hypervitaminosis. A 35
      year-old patient with distinct papilledema and double-image perception].

PMID- 10959191
TI  - [Residues of chlordane in fish in the Gulf of Gdansk].
AB  - Concentrations, composition and spatial variations of the residues of the
      pesticide Chlordane were determined in several species of fish caught in Gulf of
      Gdansk. The residues of Chlordane (cis-i trans-chlordane, cis-i trans-nonachlor,
      oxychlordane, heptachlor, heptachlor epoxide, MC4, MC5, MC6, MC7, U82 and U83)
      were found in all fish examined, however, the concentrations noted were low, i.e.
      from 0.40 to 12 ng/g wet weight. Among the Chlordane constituents and metabolites
      determined trans-naonachlor, cis-chlordane, oxychlordan, heptachlor epoxide, cis
      nonachlor, MC5, MC6 and trans-chlordane were dominated, and MC4, MC7, U82 and U83
      were minor compounds. No heptachlor residues were found in fish examined. A small
      concentrations and specific composition of the residues of Chlordane and its
      metabolites determined in fish from the Gulf of Gdansk do indicate on a distant
      sources of pollution with that pesticide--mainly transported and deposited via
      the atmosphere.

PMID- 10959192
TI  - [Organochlorine pesticide residues in tea].
AB  - Organochlorine pesticides still exist as environmental pollutants in many
      countries. In this paper, the results of monitoring of organochlorine pesticides
      in teas taken from the Polish market in 1998 year are presented. The monitoring
      included analysis of organochlorine insecticides and their metabolites (sigma
      DDT, sigma HCH, HCB, Heptachlor, Epoxide heptachlor, and Aldrin) in samples of
      black and green tea, and fruit tea. The mean concentration of the organochlorine
      compounds in the black tea ranged from 0.0002 to 0.003 mg/kg of product, and in
      the green and fruit teas from 0.0001 to 0.003 mg/kg of product depending on the
      pesticide. In no case the violation of the Maximum Residues Limits was observed.
      The results obtained in this monitoring did not differ from the results reported
      by the other authors.

PMID- 10959194
TI  - The evaluation of total dietary fibre content in standard hospital diets during
      the winter and summer seasons.
AB  - The main aim of the study was to determine the total dietary fiber in standard
      diets for hospitalized patients in winter and summer. In the randomized trial
      performed in the winter of 1995/1996 and summer 1997, we assessed the dietary
      fiber content in 12 standard diets with AOAC method. The dietary fiber in the
      tested hospital diets was derived mainly from grains--average value 12.2 g/day in
      winter and 15.8 g/day in summer. The second group of plant products to supply
      fiber in the diet were vegetables. Food portions covered an average of 11.5 g
      dietary fiber per day in winter and 8.5 g in summer. In spite of the variety of
      cheap vegetables on sale, a significantly lower content of fiber was observed in
      summer (p < 0.05). Fruits and fruit products in hospital food contained 1.4 g/day
      of fiber in winter and 1.7 g/day in summer respectively. We also made a
      simulation, where white bread, present in every diet, was replaced by dark bread.
      This let us determine the degree to which the alternative food product influences
      the diet's composition. The results demonstrate that the replacement everyday of
      eaten food products may evoke significant changes in dietary fiber contents. The
      change induced statistically significant differences between diets containing
      white bread and dark bread (p < 0.001).

PMID- 10959193
TI  - [Spectrophotometric determination of molybdenum in vegetables, food and
      pharmaceutical compounds].
AB  - A spectrophotometric method was applied for determination of molybdemun in dried
      lucerne, grains of soya, peas and bean and vitamin-mineral compound--Multi-tabs.
      The method is based on the reaction between molybdenum (VI) and 2,3,7
      trihydroxyphenylfluorone in the presence of benzyldodecyldimethylammonium
      bromide. In all samples it was possible to determine molybdenum content directly,
      after mineralization without its preliminary separation. Accuracy of the
      determination of molybdenum were checked by the method of standard addition, or
      by comparison with producer data. To establish the precision of the method, the
      standard deviation and relative standard deviation were calculate.

PMID- 10959195
TI  - [Mass catering for school children in Poland].
AB  - The assessment of organization and quality of nutrition was done in 184 urban and
      156 rural schools in 1998 to obtain information about changes in that aspect
      during last few years. Data was collected using questionnaire method. The
      analysis of obtained results showed that the per-cent of schools organizing one
      form of nutrition in towns (95.1%) was higher than in villages (64.1%), but the
      per-cent of pupils consuming at least one meal served in school was lower in
      towns (22.2%) than in villages (31.3%). In comparison with situation in the
      beginning of the 90th nutrition was organized by significantly higher amount of
      schools but improvement of situation relevant to amount of pupils consuming
      school meals was not so significant. Urban schools the most frequently served
      full dinners, in rural schools it was often sticky bun or sandwich. Significant
      per-cent of rural schools did not serve any meal due to bad local conditions and
      financial problems. From the reason that the per-cent of pupils consuming school
      meals is too small, it is necessary to undertake actions leading to improvement
      of the situation in that aspect. These activities should be relevant to increased
      access to school meals, especially in rural area, decreased cost and quality
      improvement of these meals.

PMID- 10959196
TI  - Meal planning and its relation to the nutritional status of pre-school children
      (2-4 years old) in Egypt.
AB  - The nutritional status of children (2-4 years old) depends to great extent on the
      type of food they eat. The meal planning in the family is affected by many
      factors especially nutritional habits, social-economic status of the family and
      the availability of food. This paper presents the results of the questionnaire
      studies of nutrition of pre-school children in Egypt with the special emphasis
      given to social-economic status and education level in the families. The results
      show the relationship between education, availability, size of family and
      nutritional quality of meals planning by housewife.

PMID- 10959197
TI  - General assessment of the influence of a municipal landfill site and
      environmental factors on the occurrence of keratinolytic fungi in soil.
AB  - The study was to generally determine the influence of a municipal landfill site
      and environmental factors on the distribution of keratinolytic fungi in soil. The
      landfill site in Sosnowiec was selected for examination. Keratinolytic fungi
      occurred abundantly in soils of the landfill site examined and its surrounding
      area. Of 495 soil samples (Petri dishes) examined, 379 (76.56%) were found to be
      positive for keratinolytic fungi. Altogether, 1131 strains from 26 species were
      isolated from the samples. Among the fungi, some species with pathogenic
      properties (Microsporum racemosum, M. cookei, M. gypseum, Aphanoascus fulvescens
      and Scopulariopsis brevicaulis) were recorded. The influence of environmental
      factors on the qualitative and quantitative composition of keratinolytic fungi in
      the soils was complex. Among these factors, exchangeable acidity (pH in 1 M KCl,
      in particular), faecal bacterial contamination and the level of water deficit in
      soil were the most important. The conclusion has been drawn that municipal
      landfill sites are the sources of potentially pathogenic fungi with keratinolytic
      properties.

PMID- 10959198
TI  - [Detection and isolation of bacteria of Legionella species from the water
      environment].
AB  - The aim of this work was to find method of isolation of bacteria of genus
      Legionella from water environment. Were used reference strains such as: L.
      pneumophila ATCC 33152, strains of bacteria contaminated water samples: E. coli
      ATCC 35218, S. aureus ATCC 12600, Str. faecalis ATCC 29212 and P. aeruginosa-
      strain from own collection, isolated from water environment. Because of the slow
      growth of bacteria of genus Legionella and dangers of contamination the
      preliminary treatment of examined water samples should be done. Water samples
      inoculated with standard strains of bacteria before inoculation by plated
      membrane filtration or plated directly methods were undergone acid pretreatment
      (acid buffer pH 2.2) and heat pretreatment (temp. 50 degrees C). The contact time
      used for studies was respectively 10,20,30 min. and 30, 45 min. The best time
      used for acid treatment procedure was 10 min., for heat treatment procedure was
      30 min. Such adjust parameters of preliminary treatment of water samples should
      reduce enough growth of non-Legionella organisms and not to influence the growth
      of searched Legionella strains. The researches showed that the most successful of
      isolation is membrane filtration method, where filters are directly placed on the
      culture medium. In studies buffered charcoal yeast extract agar medium with
      cysteine, activated charcoal and selective supplements were used. The growth of
      bacteria on the cellulose, polycarbonate and polyvinylidene fluoride filters were
      compared. The best results were achieved with cellulose and polyvinylidene
      fluoride filters. Growth of colonies of bacteria on the filters should be
      examined between 3rd and 7th days of incubation period at 37 degrees C and 90%
      relative humidity. Legionella forming colonies growing on membrane filters are
      shining with smooth edge, cream or white. On the polyvinylidene fluoride filters
      around colonies clear zones are observed.

PMID- 10959199
TI  - [The effect of intensive traffic noise on well-being and self-assessed health
      status of urban population].
AB  - In the study health situation of inhabitants and their subjective reaction to
      different acoustic conditions in their place of living were analysed. Comparison
      of residents who spend most of the time in rooms at a street side with the
      residents who lived in rooms at a yard side revealed significant differences
      between the groups in mental state and self assessed health status. People, who
      live in worse acoustic conditions more often complain about difficulties and
      disturbances in different daily activities. They also more often reported
      different ailments, of which the most important are problems connected with
      cardiovascular system, feeling tiredness after night sleep, frequent nervousness
      and irritation. This group of people more often takes pain killers and
      tranquillisers. However, there was no difference between the groups in reporting
      diseases that could be associated with noise and were confirmed by physician.
      Observed differences in reporting negative symptoms and reactions mentioned above
      were not related to socio-economic and behavioral factors such as: gender, age,
      economical conditions or smoking which have similar distribution in both the
      groups.

PMID- 10959200
TI  - [What is your diagnosis? Subperiosteal cortical metastases of a non-small-cell
      bronchial carcinoma (adenocarcinoma) of the right tibia, e.g. "cookie bite
      lesion"].

PMID- 10959201
TI  - [Value of the Valsalva maneuver for evaluating systole heart function].
AB  - Many tests and examinations are used for diagnosing heart failure. Their accuracy
      tends to vary, echocardiography representing the gold standard. The Valsalva
      maneuver involves an easy-to-perform test for assessing the cardiac ejection
      fraction. The present study investigated the power of the Valsalva test in
      patients who received an echocardiography for various indications. A total of 153
      patients were examined, some recruited from private practices, some from
      different hospitals. An echocardiographically measured left-ventricular ejection
      fraction of 45% was set as the limit value. 30 patients had an ejection fraction
      of less than 45%, signaling a relevant systolic dysfunction. The sensitivity of
      the Valsalva test for detecting impaired function was 70% and its specificity
      72%. The positive predictive value was 39% and the negative predictive value 90%.
      This means that when the Valsalva test produces a normal result and the EKG is
      also normal, the likelihood that the patient has no relevant systolic dysfunction
      is very great. The Valsalva test is cost-effective, quick and easy to perform and
      useful for evaluating left-ventricular pump function.

PMID- 10959203
TI  - [Atopic neurodermatitis--therapy in high altitude climate].
AB  - Climatotherapy of atopic dermatitis in a high alpine climate is a well
      established therapy that meets the currently growing demand for a holistic
      approach in the treatment of this skin condition. The effectiveness of
      climatotherapy was evaluated in 97 patients with atopic dermatitis who were
      treated at the Zurich High Mountain Clinic in Davos during the period 1990-1994.
      The period of hospitalisation averaged 32 days. Upon discharge, 89% of patients
      were symptom-free or much improved. According to the patients' subjective
      recollection after a time interval of at least one year, 70% recalled being
      symptom-free or much improved at discharge. In the first year after
      climatotherapy, 81% of patients suffered a relapse. Nevertheless, in 56% the
      severity of the atopic dermatitis was reduced, and 74% of the patients who had
      previously been unable to work were able to resume their occupation. Before
      treatment, 73% of the patients were on corticosteroids, 14% systemically. The
      latter could be discontinued in all but one case; local steroids could be
      discontinued in 71% of cases. 62% of the patients had also tried "alternative"
      medical treatments and remedies, the majority with no measurable success. Thus,
      climatotherapy is a successful treatment for atopic dermatitis, but a mild
      relapse is to be expected. The popular, but less successful "alternative" medical
      treatment of atopic dermatitis needs to be evaluated scientifically according to
      international medical standards.

PMID- 10959202
TI  - [Pregnancy prevention from the viewpoint of women (1): Patient counseling by the
      general practitioner is rated as "very good". Women assess the pill as an
      effective and safe contraception method. A representative survey].
AB  - In this opinion poll, 1000 women from Switzerland aged 15 to 45 years were asked
      about their use of contraceptives. The most favorite contraceptive is the pill
      (31%); however, it is more popular among younger women than older ones. Safety of
      contraception is mentioned as the main advantage of the pill. In second and third
      place come the condom (17%) and the intrauterine device and sterilization (6%
      each). The reasons for choosing one or the other type of contraception and the
      sources of information are discussed. Information and counselling from the family
      doctor was rated as "very good" and from the gynecologist as "good" to "very
      good".

PMID- 10959204
TI  - [Some viewpoints on ear cleaning].
AB  - The present paper discuss the cleaning of the external auditory canal. It is
      purpose of this article to show that the insertion of foreign bodies in form of
      cotton buds, into the ear, is absolutely unnecessary and may be a dangerous
      practice. We conclude that cotton-tipped swab use may be associated with cerumen
      accumulation.

PMID- 10959205
TI  - [Case from general practice. Splenomegaly. Hairy-cell leukemia].

PMID- 10959206
TI  - [Comment on: Volz A, Monsch A.U., Zahno A., Wettstein A., Stahelin H.B., Grunig
      R.: What did Alzheimer disease cost Switzerland in 1998? A preliminary analysis].

PMID- 10959207
TI  - Caribbean Health Research Council 45th annual meeting. Trinidad, April 19-22,
      2000. Abstracts.

PMID- 10959208
TI  - The biology of aging.
AB  - Nothing has been demonstrated to slow or reverse the primary aging process in
      humans; instead, the factors that are known to affect longevity do so by their
      influence on disease development, which is part of secondary aging. Preventive
      strategies against secondary aging are aimed at maintaining health and functional
      capacity and rectangularizing, rather than extending, the survival curve.
      Interventions for preventive geriatrics and successful aging include a low-fat,
      low-energy diet with a high content of fruits and vegetables; exercise; and
      hormone replacement.

PMID- 10959209
TI  - Epidemiology of sarcopenia.
AB  - There are few epidemiological data to estimate the prevalence of sarcopenia, nor
      is there a standard of morbidity that defines the degree of disability and
      consequently the seriousness of this problem. This article reviews data on
      prevalence, examines different aspects of measurements, and discusses the policy
      ramifications of establishing a specific definition of sarcopenia.

PMID- 10959210
TI  - Age-related changes in muscle.
AB  - Sarcopenia is a debilitating condition that occurs with senescence. The present
      study places this entity in the context of life expectancy, then discusses the
      mechanism of muscle loss. The findings show deficits in muscle protein synthesis
      with advancing age and suggest that these deficits are specific to certain muscle
      protein components. Synthesis rates of myosin heavy chain and mitochondrial
      protein decline with advancing age; however, there are no specific conclusions as
      to causation of these reduced muscle protein syntheses. The utility of protein
      dynamic measurements in evaluating potential therapies is discussed.

PMID- 10959211
TI  - Techniques to measure testosterone in the elderly.
AB  - In today's clinical and research settings, there is an unfortunate lack of
      consistency for the term "measuring testosterone status." This term is often used
      to refer to a measure of biologic androgen activity rather than the specific
      measurement of the chemical concentration of the testosterone steroid molecule.
      Even the measurements of chemical concentrations show considerable methodologic
      differences. This is true for measurements in elderly men, as well as in other
      populations, including women. All of the current methods for measuring total
      testosterone have limitations, especially with regard to low concentrations. In
      addition, unresolved questions concerning the active form of the hormone preclude
      definitive determination of which form of testosterone and which other androgen
      hormones are best suited for measuring androgen activity. When measurement
      techniques are compared, the numbers correlate with each other but certainly do
      not represent the same value. There is a need for a consensus as to which forms
      of hormones should be measured to best assess androgen status, and there is a
      need to standardize the procedures used to measure these hormones.

PMID- 10959212
TI  - Androgen receptors in prostate and skeletal muscle.
AB  - Regulatory control of the androgen receptor has been studied most extensively in
      prostatic tissue. Additional information has been obtained from the study of
      androgen receptors in pituitary and hypothalamic tissues, and these results can
      be extrapolated to regulatory mechanisms in both prostate and skeletal muscle.
      The present work provides a brief summary of studies on androgen action on
      muscle, gives an overview of mechanisms of androgen action on target tissues, and
      focuses on several aspects of regulation of androgen receptor (AR) gene
      expression. These include some characteristics of AR gene transcription start
      sites; the role of the cyclic adenosine monophosphate, protein kinase C, and
      protein kinase A pathways in mediating androgen receptor function; and tissue
      variable regulatory elements inhibiting AR gene expression.

PMID- 10959213
TI  - Molecular biology of the androgen receptor.
AB  - The androgen receptor is a member of a superfamily of nuclear transcription
      factors that mediate the action of steroid hormones. When activated by ligand
      binding, these transcription factors bind to specific DNA sequences on target
      genes and regulate the transcriptional activity of those genes. Various genes
      have been identified that are regulated by androgens, including prostate-specific
      antigen (PSA). PSA contains an upstream glucocorticoid response element/androgen
      response element, so it is believed that androgens directly regulate its
      transcription rate. Despite this, posttranscriptional regulation through
      stability of the messenger RNA product is believed to be a major mechanism of
      androgens' effects.

PMID- 10959214
TI  - Prostatic steroid 5 alpha-reductase, an androgen metabolic gene.
AB  - Prostate cancer risk is highest in African Americans, lowest in Asians, and
      intermediate in Caucasians and Latinos. The data clearly suggest that
      environmental and genetic factors are involved. Investigation of the genetic
      factors suggests that allelic variation in the SRD5A2 gene is partially
      responsible for the striking racial and ethnic variations in risk.

PMID- 10959215
TI  - Treatment of endocrinologic male sexual dysfunction.
AB  - Erectile dysfunction affects 20 million to 30 million men in the United States,
      and it has been reported that a significant number of impotent men (2.1% to 23%)
      have subnormal serum testosterone levels. A decline in serum levels of
      testosterone accompanies normal aging in men; however, the pathophysiological and
      clinical consequences of this decline are unknown. Appropriate hormonal therapy
      for men with hypogonadism requires an understanding of the normal physiologic
      regulation of the testes and the pathophysiology of underlying testicular
      dysfunction. This article reviews those mechanisms.

PMID- 10959216
TI  - Primary osteoporosis in men: role of sex steroid deficiency.
AB  - This presentation explores the role of estrogen deficiency in the causation of
      age-related bone loss in both sexes. Over life, women experience 2 phases of bone
      loss--an early, rapid postmenopausal phase that classically has been attributed
      to estrogen deficiency and a subsequent slow phase that previously has been
      attributed to aging changes. Men have only the slow continuous phase of bone
      loss. The hypothesis is developed here that most of the slow late phase in aging
      women and much of the slow continuous phase in aging men both are due to estrogen
      deficiency.

PMID- 10959217
TI  - The effects of androgens on osteoblast function in vitro.
AB  - The relative contributions of androgens and estrogen to bone metabolism are still
      being defined. To directly assess androgen effects on bone cells, we have
      developed human osteoblastic cell models expressing the androgen receptor. This
      approach is distinct from studies that have used a variety of transformed cell
      lines, in that the latter studies showed variability in the results.
      Investigation into androgen effects on bone has been overshadowed by interest in
      estrogen effects.

PMID- 10959218
TI  - Testosterone and muscle protein metabolism.
AB  - This presentation discusses recent investigations into testosterone's effects on
      muscle protein metabolism. Protein synthesis is the principal end point, but
      protein breakdown and the availability of an amino acid pool are important to the
      process of net muscle protein synthesis. The effects of other hormones--including
      growth hormone, oxoandrolone (a synthetically derived testosterone), and
      androstenedione--on muscle protein synthesis also are discussed. Effects in both
      normal and elderly men are considered.

PMID- 10959219
TI  - Androgen effect on insulin action and glucose metabolism.
AB  - Our understanding of the effect of androgens on insulin action and glucose
      metabolism is incomplete. Data derive from several different models and methods,
      and the limitations of each must be considered. Results suggest that in humans,
      low-dose testosterone (replacement dosages) may increase insulin action; high
      dose testosterone (supplemental or pharmacologic dosages) decreases insulin
      action; and dehydroepiandrosterone appears to have no effect.

PMID- 10959221
TI  - The dose-dependent effects of testosterone on sexual function and on muscle mass
      and function.
AB  - Testosterone dose-response relationships are central to the issue of testosterone
      replacement therapy, within the context of both hypogonadal men and older men
      with declining testosterone levels. Dosages are also important when considering
      anabolic applications of testosterone for treating sarcopenia associated with
      chronic illness. The critical issue is whether increases in muscle mass and
      function can be achieved with dosages that will not adversely affect lipid
      profile, cardiovascular risk, and the prostate. The dose-response relationship
      and mechanisms of androgen action on the muscle for controlling it are being
      investigated.

PMID- 10959220
TI  - Androgen effect on body composition and fat metabolism.
AB  - Recognizing the adverse metabolic effects of predominantly visceral body fat
      distribution associated with low testosterone levels, researchers have
      investigated the effects of androgen treatment on body fat distribution in men.
      This presentation reviews the results of research on acute and longer-term
      effects of treatment with testosterone and dihydrotestosterone. Methods for
      investigating these results, including measurement of lipoprotein lipase activity
      and of radiolabeled fat uptake and turnover, are described and discussed.

PMID- 10959222
TI  - Experience with testosterone replacement in the elderly.
AB  - To date, most of the studies of androgen replacement have been done with healthy
      older men (age > or = 55 years), and almost no data are available for frail
      elderly individuals. Treatment effects that make a relatively small difference in
      younger, more robust individuals may have a greater effect on the elderly, whose
      improvement in functioning and level of activity may be more dramatic. However,
      the frail elderly individual is also more vulnerable to adverse effects from
      treatment, and these potential risks and benefits must be weighed.

PMID- 10959224
TI  - The pros and cons of testosterone replacement in elderly men: a panel discussion.

PMID- 10959223
TI  - Testosterone replacement and the physiologic aspects of aging in men.
AB  - Clinical and epidemiologic studies, along with basic scientific research, have
      shown a trend toward androgen deficiency in aging males. The focus of the
      clinical investigations described here is to determine whether testosterone
      deficiency is a physiologic cause of the aging process and whether testosterone
      replacement might prevent or ameliorate a decline in quality of life associated
      with age-related decline in physical and psychological functioning.

PMID- 10959225
TI  - Pathogenetic mechanisms of diabetic neuropathy: lessons from animal models.

PMID- 10959226
TI  - Dystrophin superfamily complexes are different in muscle and the nervous system.

PMID- 10959227
TI  - Electrodiagnostic studies in the Dutch multicentre Guillain-Barre study: a
      review.

PMID- 10959229
TI  - Effects of hypoxia and severity of diabetes on Na,K-ATPase activity and
      arachidonoyl-containing glycerophospholipid molecular species in nerve from
      streptozotocin diabetic rats.
AB  - The pathogenesis of experimental diabetic neuropathy is associated with the
      development of endoneurial hypoxia. Exposure of normal rats to hypoxic conditions
      has previously been shown to reduce nerve conduction velocity. To study the
      biochemical effects of hypoxia further, streptozotocin-induced diabetic and age
      matched nondiabetic rats were maintained in air containing 10% oxygen for nine
      weeks. As compared to nondiabetic rats kept in room air, sciatic nerve Na,K
      ATPase activity was decreased 38% in nondiabetic, hypoxic rats and tended to be
      lower in diabetic animals maintained in a normoxic environment. However, the
      enzyme activity was unchanged in diabetic, hypoxic rats, suggesting the existence
      of an undefined compensatory interaction between these two conditions.
      Arachidonoyl-containing molecular species (ACMS) of phosphatidylcholine and
      phosphatidylethanolamine were substantially depleted in nerves from diabetic
      rats. Hypoxia alone also caused a lesser depletion of some but not all of these
      ACMS. However, the two conditions together did not produce a further decrease,
      consistent with the concept that the same mechanism is responsible for loss of
      ACMS in hypoxia and diabetes. To examine the effects of severity of diabetes on
      these parameters, groups of rats were injected with either 50 mg/kg or 100 mg/kg
      streptozotocin. The latter group was maintained by administration of minimal
      insulin doses and the experiment was terminated after 3 weeks. Serum glucose in
      rats that received the high dose of drug averaged 12% higher than in the low dose
      group. As compared to nondiabetic rats, Na,K-ATPase activity was reduced 32-36%,
      but there was no difference in activity between the two diabetic groups. However,
      there was a greater loss of ACMS in the more severely hyperglycemic rats. In rats
      that received comparable streptozotocin doses, measurement of ACMS depletion
      after 3, 9 and 32 weeks of diabetes revealed the loss is progressive with time.
      Thus, glycerophospholipid ACMS is a sensitive index of the severity and duration
      of experimental diabetic neuropathy.

PMID- 10959228
TI  - Acute painful diabetic neuropathy: two patients with recent insulin-dependent
      diabetes mellitus.
AB  - Two young men developed an acute painful peripheral neuropathy a few weeks after
      being diagnosed to suffer from an insulin-dependent diabetes mellitus. In both
      cases, peripheral nerve biopsy exhibited a few features of acute axonal
      degeneration. Additionally, in the first case there was a lymphocytic infiltrate
      around an endoneurial capillary, and in the second case there were several mast
      cells in the endoneurium of every fascicle examined. A few months later, the
      acute pain had disappeared in both cases. Only a few cases of acute painful
      diabetic neuropathy have been reported so far. A vascular origin seems unlikely
      and metabolic disorders are probably due to a contemporary severe weight loss. An
      auto-immune mechanism is an alternative explanation.

PMID- 10959230
TI  - Acrylamide intoxication modifies in vitro responses of peripheral nerve axons to
      anoxia.
AB  - Decreased axolemmal Na+/K(+)-ATPase activity has been considered as a possible
      mechanism for peripheral nerve axon damage induced by acrylamide (ACR) or 2,5
      hexanedione (HD). Reduced activity of this enzyme is also presumed to be the
      basis of peripheral nerve resistance to ischemia or hypoxia associated with other
      neuropathies (e.g., diabetes). In the present study, we tested the hypothesis
      that peripheral nerve of ACR (50 mg/kg/d x 10 d) or HD (400 mg/kg/d x 20 d)
      exposed rats are resistant to oxygen-limiting conditions as a result of reduced
      axonal Na+/K(+)-ATPase activity. As an index of resistance, effects of in vitro
      anoxia on subaxonal concentrations of Na, K and Ca were assessed in isolated
      segments of tibial nerve from control and neurotoxicant-treated animals. Results
      show axons from HD rats were not resistant to anoxic challenge; i.e., axons
      exhibited disrupted elemental composition comparable to anoxic control changes.
      In contrast, ACR-exposed axons displayed anoxic resistance. Ouabain-exposed
      tibial axons subjected to anoxic conditions were also resistant, but the
      corresponding elemental pattern did not resemble that associated with ACR axons.
      Moreover, ACR axons were capable of maintaining elemental gradients during
      normoxic exposure which should not be possible if Na+ pump activity is depressed.
      Considered together, these data are not consistent with a role for diminished
      Na+/K(+)-ATPase activity in neurotoxicant-induced peripheral axonopathy. We also
      assessed the ability of ACR- and HD-exposed tibial nerve axons to recover from
      anoxia. Unlike control fibers which can fully restore normal elemental
      composition, neurotoxicant-exposed axons were incapable of such restoration.
      These data suggest the axonal machinery responsible for post-anoxia recovery
      (e.g., energy metabolism, ion translocation, Ca2+ and free radical buffering) is
      compromised by ACR or HD intoxication.

PMID- 10959232
TI  - Repair of the mandibular branch of the rat facial nerve through transmedian
      grafting in one or two stages. Morphological evaluation.
AB  - This study examined by electron microscopy the normal fibre composition of the
      mandibular branch (MB) of the rat facial nerve and the outcome of axon
      regeneration in the MB after transmedian grafting in one or two stages. The
      average normal MB contained 2,185 axons, 17% of which were unmyelinated. The
      myelinated axons had a unimodal diameter distribution (range 1.5-9.5 microns,
      mode 4.5 microns). After superior cervical ganglionectomy, the MB lost 1/3 of the
      C-fibres and 10% of the myelinated axons. In neonatally capsaicin-treated rats
      the occurrence of unmyelinated axons was reduced by about 50%. After repair in
      one or two stages the MB contained more myelinated and unmyelinated axons than
      normal. The myelinated axons showed a unimodal size distribution with a subnormal
      diameter range. Statistical comparisons showed that MBs from both experimental
      groups were significantly abnormal with respect to total axon number as well as
      numbers of unmyelinated and myelinated axons. In these respects the grafted MBs
      did not differ significantly from each other. However, the myelinated axons in
      MBs from one-stage cases showed larger mean and maximum diameters compared to MBs
      from two-stage cases. These data suggest that the normal MB of the rat contains
      myelinated and unmyelinated sympathetic axons and that about half the C-fibres in
      the normal MB come from capsaicin-sensitive sensory neurons. The comparison of
      the two reparative procedures used provides evidence in favor of the one-stage
      alternative.

PMID- 10959231
TI  - Effects of aging on nerve conduction block induced by bupivacaine and procaine in
      rats.
AB  - To test the hypothesis that the dose requirement for local anesthetics is changed
      in aged animals, the effects of two different local anesthetics on nerve
      conduction block were tested in young and old rats. Young (6 months) and old (27
      months) male Fisher-344 rats were anesthetized with intraperitoneal pentobarbital
      and diazepam. Stimulating electrodes were placed in the sciatic notch and in the
      ankle and recording electrodes were placed distally in the ipsilateral foot to
      record evoked electrical activity of the interosseous muscles. Motor nerve
      conduction velocity was significantly less in old (48.8 +/- 3.9, mean +/- SD
      m.sec-1) than in young rats (56.4 +/- 10.3 m.sec-1) (P < 0.05). To test the
      effects of aging on conduction block, equipotent doses of bupivacaine (0.2%), an
      amide-linked local anesthetic, or procaine (0.6%), an ester-linked local
      anesthetic, were injected next to exposed sciatic nerves and evoked electrical
      activity was monitored following repeated stimulation at the sciatic notch. At 10
      minutes after injection, bupivacaine produced significantly greater nerve block
      in old rats (100 +/- 0.0%) than young rats (29.8 +/- 41.6%) (P < 0.01); the
      difference for procaine (old 67.5 +/- 40.4% vs. young 30.4 +/- 35.3%) was not
      statistically significant. The lower dose requirement for bupivacaine, and the
      apparent differences compared to procaine, may have implications for the use of
      local anesthetics in an aging patient population.

PMID- 10959233
TI  - Anti-ganglioside antibody and neuropathy: review of our research.
AB  - Some patients developed Guillain-Barre syndrome (GBS) after the administration of
      bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni
      enteritis frequently have IgG antibody to GM1 ganglioside. Fisher's syndrome
      (FS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. We
      showed the existence of molecular mimicry between GM1 and lipopolysaccharide
      (LPS) of C. jejuni isolated from a GBS patient, and that between GQ1b and C.
      jejuni LPSs from FS patients. Several lines of evidence suggest a pathogenic role
      for anti-ganglioside antibodies. Some patients developed sensorimotor
      polyneuropathy after anti-GD2 antibody administration. Anti-GM1 antibody can
      block motor nerve conduction. The molecular mimicry between infectious agents and
      gangliosides may function in the production of anti-ganglioside antibodies and
      the development of GBS and FS. Anti-GQ1b IgG antibody is detected also in
      Bickerstaff's brainstem encephalitis and acute ophthalmoparesis, which suggests
      that these conditions are categorized as autoimmune diseases related to FS. Since
      a tryptophan-immobilized column effectively adsorb anti-GQ1b IgG antibody,
      immunoadsorption with the column should be considered as an alternative form of
      plasmapheresis for the anti-GQ1b IgG antibody syndrome.

PMID- 10959234
TI  - Antibodies to glycolipids and cholera toxin B subunit do not initiate Ca++
      signaling in rat Schwann cells.
AB  - Antibodies to glycolipids have been implicated in the pathogenesis of several
      immune-mediated PNS demyelinating diseases. This study focuses on antibodies to
      galactocerebroside (GalC) and sulfatide and on the B subunit of cholera toxin
      (CTB), which reacts with GM1 ganglioside, to examine whether these agents have
      any direct effects on Schwann cells (SC) as measured by Ca++ responses. While
      surface levels of GalC and sulfatide were markedly upregulated by 8 Br-cAMP
      treatment, as reported by others, very little expression of surface GM1
      ganglioside was detected with or without 8 Br-cAMP treatment. Schwann cells,
      under either condition, showed no changes in intracellular Ca++ levels when
      exposed to purified monoclonal antibodies reacting with GalC or sulfatide. Thus
      upregulation of surface levels of GalC or sulfatide does not lead to antibody
      induced Ca++ influx, in contrast to previous findings in mature oligodendrocytes
      (OLs) exposed to antibodies to GalC. Further, cross-linking with one of the
      antibodies (R-mAb) did not produce Ca++ responses. No Ca++ responses were
      elicited by CTB in Schwann cells either with or without 8 Br-cAMP treatment.
      Since surface binding of CTB was very low and sparsely punctate in Schwann cells
      +/- 8 Br-cAMP, we tested whether increasing levels of GM1 ganglioside on the
      surface would lead to induction of a Ca++ signaling pathway, as reported for
      fibroblasts. GM1 ganglioside on the surface of SC was markedly increased by
      exposing cells to exogenous GM1 ganglioside, but no Ca++ responses were observed
      in the treated cells. Thus undifferentiated or partially differentiated SC lack
      the glycoconjugate-mediated Ca++ signaling pathways found in mature OLs or
      fibroblasts.

PMID- 10959236
TI  - Neurotrophic influence of sciatic nerve-released factors on isolated adult
      motoneurons in vitro.
AB  - The present experiments were designed to determine whether the cells of the
      distal portion of a sectioned peripheral nerve release diffusible factors that
      exert a trophic influence on isolated adult motoneurons in vitro, whether the
      release of those factors increased with time following nerve section, and to
      characterize the neurotrophic influences. In defined medium, motoneurons started
      to extend processes only after 1 day. However, when co-cultured with a length of
      sciatic nerve, denervated one week prior to being placed in the co-cultures, the
      motoneurons began to extend processes within one day, and by four days the
      average process length was 10 times longer than that of control neurons. While
      control neurons extended 4 processes, the co-cultured neurons extended only a
      single process, and the processes were thinner and straighter than those of the
      control neurons, and they lacked lamellipodia, typical of control neurons.
      Although one-week predenervated peripheral nerve initially had a greater
      influence on motoneuron process outgrowth than a freshly isolated piece of
      sciatic nerve--after three days the processes were 33% longer--, this difference
      decreased with time, so that by seven days this difference was only 7%. Thus time
      was required for the release of the neurotrophic factor following nerve section.
      Both predenervated and freshly sectioned sciatic nerves had the same influences
      on the number and morphology of processes of the co-cultured motoneurons. The
      neurotrophic influence of medium conditioned for seven days by a piece of sciatic
      nerve was the same as that seen when the cells of the peripheral nerve were in
      the medium. Nerve growth factor did not induce process elongation from the
      motoneurons. In addition, antibodies against nerve growth factor, known to block
      its bioactivity, did not diminish the neurotrophic influence of the sciatic nerve
      conditioned medium on the motoneurons. These results indicate that factors
      released from the cells of a sectioned peripheral nerve have a potent
      neurotrophic influence on adult motoneurons, the release of these factors
      increases with time following nerve section, and that the factor does not appear
      to be nerve growth factor. These observations suggest that the cells of the
      denervated distal nerve play an important physiological role in vivo, in
      releasing diffusible factors that act on motoneurons to promote significant
      process outgrowth, regulate the number of processes extended, and modify the
      morphology of the processes, leading to reinnervation of the distal nerve stump.

PMID- 10959235
TI  - Regulation of glucose transport in cultured Schwann cells.
AB  - Glucose is the major source of metabolic energy in the peripheral nerve. Energy
      derived from glucose is mostly utilized for axonal repolarization. One route by
      which glucose may reach the axon is by crossing the Schwann cells that initially
      surround the axons. Considering the ability of neurons to control many glial cell
      functions, we postulated that Schwann cell glucose transporters might be
      transiently regulated by axonal contact. Glucose transport was studied in a
      cultured, differentiated rat Schwann cell line stably expressing SV40 T antigen
      regulated by a synthetic mouse metallothionein promoter. 3[H]-2-deoxy-D-glucose
      uptake was measured in cultured cells in basal and in various experimental
      conditions. Glucose transporter gene expression was determined after RNA
      isolation from cultured cells through Northern and RNAse protection assay. In
      vitro, Schwann cells were found to express high-affinity, insulin-insensitive,
      facilitative glucose transporters and predominantly GLUT1 mRNA. Schwann cell 2
      deoxyglucose uptake was increased by axolemmal membranes or forskolin but
      unchanged by elevated glucose levels. Regulation of Schwann cell glucose
      transporters by axolemma and their resistance to glucose-induced down-regulation
      suggest extrinsic rather than intrinsic regulation that might enhance Schwann
      cell vulnerability to glucotoxicity.

PMID- 10959237
TI  - Relation between putative afferent axons and the glia limitans in rat motor
      roots.
AB  - The law of Magendie states that ventral roots channel efferent axons from the
      spinal cord to the periphery, while dorsal roots channel afferent axons from the
      periphery into the spinal cord. As primary afferent C-fibres occur in mammalian
      ventral roots, this law has been questioned. However, other observations suggest
      that ganglionic axons do not enter the spinal cord via ventral roots. The present
      paper examined, by double labelling immunohistochemistry, the relation between
      putative peripheral afferents and the PNS/CNS transition in the trigeminal motor
      root and in selected spinal ventral roots of the rat. The afferents were labelled
      with antibodies against vasoactive intestinal polypeptide, substance P or
      calcitonin gene-related peptide. The glia limitans at the PNS/CNS transition was
      defined with antibodies against glial fibrillary acidic protein. The results
      showed that no immunoreactive axons occurred in the trigeminal motor root.
      However, in all ventral roots examined, labelled axons were frequently observed.
      While some of these ended blindly, looped or branched in the rootlets, others
      shifted to the pia mater. Immunoreactive axons crossing the glia limitans at the
      PNS/CNS transition were not observed. Thus, the results obtained support the law
      of Magendie.

PMID- 10959238
TI  - Repair of the mandibular branch of the rat facial nerve through transmedian
      grafting in one or two stages. Functional evaluation.
AB  - A previous study examined the morphological outcome of axonal regeneration in the
      mandibular branch (ramus marginalis mandibulae) of the rat facial nerve after
      transmedian nerve grafting in one or two stages. The present study supplements
      the morphological data with a functional evaluation. Recordings of the force of
      tetanic muscle contractions elicited through stimulation of the mandibular branch
      showed that upper and lower lip data obtained from animals grafted in one stage
      did not differ significantly from control data. However, animals grafted in two
      stages exhibited significantly lower muscle forces compared to one-stage data and
      to control data. Electromyographic recordings of the M-response showed multiple
      prolonged potential fluctuations with subnormal amplitudes in grafted cases. In
      both groups of grafted rats, the mean voltage amplitudes recorded from the upper
      lip were weaker than the amplitudes seen at the angle of the mouth or the lower
      lip. The two-stage cases exhibited the most obvious deficit. In conclusion, the
      present results show that, with respect to the functional restoration achieved
      three months after nerve injury, repair through transmedian grafting in one stage
      gives better results than repair in two stages. This finding, which conforms with
      previous morphological data, suggests that the one-stage procedure should be
      considered for clinical use.

PMID- 10959239
TI  - Effects of shaking on the sensitivity of neuromuscular transmission in vitro to d
      tubocurarine and neomycin in mice.
AB  - The effects of continuous shaking after birth were examined on the sensitivity of
      neuromuscular transmission to d-tubocurarine (dTc) and neomycin (NMC) in various
      nerve-muscle preparations from male mice of the ddY strain. Newborn mice were
      subjected to continuous reciprocal shaking with an amplitude of 2.5 cm at a
      frequency of 2 cycles per second until they reached 13 weeks of age. Some of them
      were returned to conventional breeding conditions for 4 weeks at 13 weeks of age.
      Nerve-muscle preparations were made from the left phrenic nerve and the diaphragm
      muscle (DPH), the sciatic nerve and the soleus muscle (SOL), and the sciatic
      nerve and the extensor digitorum lungus muscle (EDL) of 13- or 17-week-old male
      mice. The results revealed that the shaking augmented the sensitivity of SOL and
      DPH to dTc, it reduced the sensitivity of all the preparations to NMC, it reduced
      the rate of spontaneous release of transmitter in SOL and it increased the rate
      of evoked release of transmitter in DPH. Furthermore, these alterations
      disappeared upon cessation of shaking. These results suggest diversity in the
      plasticity of neuromuscular transmission and, moreover, that some changes might
      be reversible.

PMID- 10959240
TI  - Peripheral neuropathy in chronic respiratory insufficiency.
AB  - Peripheral neuropathy commonly occurs in patients with chronic obstructive lung
      disease (COPD). We report the presence of peripheral neuropathy in 19 of our 30
      COPD patients (63.3%): 7 patients had clinical signs of a symmetric motor and
      sensory polyneuropathy, 12 patients had only subclinical evidence of peripheral
      nervous system involvement. Neurophysiological studies showed low amplitude
      compound muscle action potentials (CMAP) and sensory action potentials (SAP) with
      only slight reduction of nerve conduction velocity in affected patients: these
      data confirm an axonal polyneuropathy. The severity of the peripheral nervous
      system involvement in COPD patients was correlated with hypercapnia, the degree
      of disability and thus with the severity of COPD. Hypoxia, age and duration of
      the disease were not related with the presence of polyneuropathy. Improvement of
      respiratory function produced slight but progressive improvement of neurological
      symptoms. Within one year, also neurophysiological studies revealed a progressive
      and statistically significant improvement in CMAP and SAP amplitude and motor and
      sensory conduction velocity and, in some cases, normal electromyography.

PMID- 10959241
TI  - Upregulation of growth associated protein 43 expression and neuronal co
      expression with neuropeptide Y following inferior alveolar nerve axotomy in the
      rat.
AB  - Growth associated protein 43 (GAP 43) is an acidic membrane-bound phosphoprotein
      produced at high levels in developing and regenerating neurons. It is a substrate
      for protein kinase C and suggested to be involved in calcium-regulated release of
      axonal vesicular-contained neurotransmitters. Expression of GAP 43 has been
      demonstrated in the uninjured cat dental pulp which receives its sensory nerve
      supply from the trigeminal ganglion. The aim of this study was a detailed mapping
      of the spatial and time-dependent expression of GAP 43 and co-expression of
      neuropeptide Y (NPY) in dental peripheral target tissues and trigeminal neurons
      subsequent to inferior alveolar nerve (IAN) axotomy in rats, as background for
      later low-level laser studies. Unilateral sectioning of IAN, resulting in an
      almost complete loss of sensory nerve fibers in the ipsilateral dental pulp of
      the first molar, was performed. The avidin biotin complex (ABC) method was used
      to evaluate peripheral changes in GAP 43 expression at 4, 7 and 10 days.
      Ganglionic changes in GAP 43 and co-localization of neuronal NPY expression was
      examined at 4, 10 and 21 days using either the ABC method or double
      immunofluorescence labelling techniques and confocal microscopy. Axotomy resulted
      in an early upregulation and change in the peripheral distribution of GAP 43 in
      nerve profiles already 4 days post IAN axotomy suggesting a Schwann cell origin.
      Ten days post axotomy a pronounced upregulation of GAP 43 immunoreactivity could
      be demonstrated in neurons located in the mandibular region of the trigeminal
      ganglion, compared to the contralateral uninjured side. The peripheral and
      ganglionic upregulation of GAP 43 continued to persist at 21 days. A concomitant
      time-delayed shift and co-expression of NPY was demonstrated throughout in the
      GAP 43-upregulated ganglion cells 10 days post axotomy. Furthermore, confocal
      microscopy indicated that the intraneuronal distribution of NPY and upregulated
      GAP 43 expression showed a similar conformity and distribution in both
      perinuclear regions and cell periphery.

PMID- 10959242
TI  - Stimulation and recording from regenerated peripheral nerves through polyimide
      sieve electrodes.
AB  - This paper describes the use of a new polyimide sieve electrode as a chronic
      neural interface to stimulate and record signals from regenerated peripheral
      nerves. Flexible thin polyimide electrodes were placed in silicone chambers and
      implanted between the severed ends of the sciatic nerve in rats. The sieve part
      of the interface has 281 round via holes of 40 microns diameter, with seven
      integrated recording-stimulating electrodes arranged around via holes. Axonal
      regeneration through the via holes was demonstrated by histological and
      physiological methods over a two to six month post-implantation period in all the
      rats. The regenerated nerves were organized in fascicles corresponding to the
      grid pattern of the via holes. Longitudinal sections showed myelinated fibers,
      with normal appearance and well developed myelin sheath, crossing the via holes.
      Stimulation of the regenerated nerve through the polyimide electrode evoked
      distal muscle and nerve responses similar in amplitude to those evoked by nerve
      stimulation with hook metal electrodes. The polyimide electrodes were useful for
      recording nerve action potentials in response to electrical stimulation of the
      distal regenerated nerve, and in response to functional sensory stimulation of
      several modalities.

PMID- 10959243
TI  - Presynaptic changes of neuromuscular transmission in mice induced by passive
      transfer of plasma with anti-presynaptic membrane receptor antibodies from a
      patient with myasthenia gravis.
AB  - Electrophysiological studies were conducted in three groups of mice to determine
      the possible involvement of the antibodies to presynaptic membrane receptor
      (PsmR), a beta-bungarotoxin (beta-BuTX) binding protein, in the pathogenesis of
      myasthenia gravis (MG). Mice were untreated (untreated group, n = 8) or were
      injected (i.p.) with blood plasma from a MG patient, which contained antibodies
      to PsmR, at a dose of 1 ml per day for more than 2 months (MG plasma group, n =
      12) or with plasma from healthy subjects (normal plasma group, n = 10). Prior to
      plasma injection, cyclophosphamide was given at 300 mg/kg (i.p.) to all three
      groups. About three weeks after plasma injection, most mice of the MG plasma
      group became less mobile in comparison with those of the two control groups.
      Electrophysiological recording showed three main changes in the MG plasma group:
      (1) the increase in the frequency of miniature endplate potentials (mEPPs)
      induced by Krebs solution with high K+ concentration (17.5 mM) was significantly
      lowered, which was confirmed in mice injected with IgG (50 mg per day) from this
      patient for two days; (2) the quantal content of EPP was decreased; and (3) the
      decrement in the amplitude of a train EPP (50 Hz) was quickened. Our results
      suggest that this experimental model is different from that of Lambert-Eaton
      myasthenic syndrome and that antibodies to PsmR may also be involved in the
      pathogenesis of MG.

PMID- 10959244
TI  - Effects of trifluoperazine and promethazine on the release of transmitter quanta
      at the mouse neuromuscular junction.
AB  - The present experiments examined the effects of phenothiazine derivatives, such
      as trifluoperazine and promethazine, on the release of transmitter quanta in
      preparations of the mouse diaphragm. The frequency (F, s-1) of miniature end
      plate potentials and the quantal content (m) of endplate potentials were measured
      intracellularly at the same endplate in a bathing solution that contained 0.5-0.8
      mM Ca2+ ions and 5 mM Mg2+ ions. Trifluoperazine (4 microM) significantly reduced
      both F and m. The inhibitory effect on m, but not on F, was subject to
      competition by Ca2+ ions. Promethazine at 48 microM, but not at 16 microM,
      reduced the quantal release. It was apparent that the effect of trifluoperazine
      was competitively antagonized by Ca2+ ions at motor nerve terminals.

PMID- 10959245
TI  - Expression pattern of the peripheral myelin protein 22kDa (PMP22) in neural and
      non-neural tissue types of adult wildtype and Trembler mice--a comparative study.
AB  - The Trembler mouse was the first animal model for Charcot-Marie-Tooth disease
      type 1 (CMT1), one of the most frequent inherited peripheral neuropathies in man.
      In Trembler mouse a Gly150Asp amino acid exchange in the peripheral myelin
      protein 22kDa (PMP22) gene was identified as causative reason for this
      hypertrophic neuropathy. For most of the CMT patients suffering from the subtype
      1A a duplication of the PMP22 gene is found (gene dosage effect); but several
      PMP22 point mutations, such as that determining the TremblerJ mouse, have also
      been described. Since PMP22 is expressed in neural, as well as in non-neural
      tissues, the expression pattern of PMP22 in different tissues seems to be of
      highest interest for a better understanding of the hypothesized dual function of
      this protein. We studied different wildtype (wt) and Trembler (Tr) mouse tissues
      for PMP22 expression by means of radioactive in situ hybridization (RISH) and
      immunohistochemistry. A PMP22 expression was found in some of the non-neural and
      in all neural tissue types studied. Our in situ study clearly demonstrated, that
      PMP22 mRNA expression in non-neural tissues is not due to peripheral innervation.
      In non-neural tissues no difference in the expression pattern or intensity
      between wt and Tr mice was detectable, whereas PMP22 expression in the peripheral
      nervous system (PNS) of the Tr mouse was extremely reduced. Immunohistochemical
      analysis of sciatic nerve sections revealed the same maldistribution of PMP22 in
      Tr mice as in sural nerve biopsies of CMT1 patients.

PMID- 10959246
TI  - Congenital insensitivity to pain with anhydrosis. Report of two unrelated cases.
AB  - Two unrelated female cases of congenital insensitivity to pain with anhydrosis
      are presented. The first case was born from consanguineous parents. In both
      cases, onset of manifestation was observed in infancy with automutilation and
      recurrent fever. Both were mentally retarded. They underwent a peripheral nerve
      biopsy respectively at 3 and 33 years. A dramatic loss of unmyelinated fibers was
      observed in both cases. Myelinated fibers were also moderately reduced in number,
      especially those of smallest diameter; this loss was more marked in the second
      patient who was adult when the peripheral nerve was studied. Clusters of
      regenerating myelinated fibers were seen in both cases. Such histological
      observations might suggest a slowly progressive disorder. The cases are discussed
      together with previous reports dealing with congenital insensitivity to pain.

PMID- 10959247
TI  - Chronic relapsing multifocal sensory-motor neuropathy with conduction block.
AB  - A 47 years old man had 13 episodes of relapsing and remitting sensory-motor
      neuropathy involving the upper limbs over the last 20 years. All but the last
      episode resolved spontaneously within 2 months. Neurophysiology revealed
      multifocal motor and sensory conduction block in the upper limbs with normal
      terminal latencies. CSF analysis was normal and anti-GM1 antibodies were not
      detected. There was a dramatic clinical improvement after intravenous
      immunoglobulin treatment. This case represents an unusual multifocal variant of
      chronic inflammatory demyelinating neuropathy.

PMID- 10959248
TI  - Neuronal reorganization through oscillator formation training in patients with
      CNS lesions.
AB  - A method has been developed 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 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 can be extracted from the multi-unit impulse patterns,
      and human central nervous system (CNS) functions can be analyzed under
      physiologic and pathophysiologic conditions. With the discovery of premotor
      spinal oscillators it became possible to judge upon CNS neuronal network
      functions based on the firing patterns of these spinal oscillators. Since
      oscillatory firing has also been observed in electromyographic (EMG) single motor
      unit firing patterns, it seems possible to follow up therapeutic intervention in
      patients with spinal cord lesion 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. Since
      rhythmic, dynamic, stereotyped, symmetric movements are mainly located in the
      spinal cord and only little supraspinal drive is necessary to initiate, maintain
      (especially), and terminate them, rhythm training methods were used to enforce
      reorganization of the CNS following spinal cord and CNS lesions to improve the
      self-organization and relative coordination of spinal oscillators which became
      pathologic in their firing following CNS lesion. Paraparetic, tetraparetic and
      brain-lesioned patients relearned running and other movements by an oscillator
      formation training. This development in neurorehabilitation is in accordance with
      those of theoretical and computational neurosciences which consider self
      organization of neuronal networks. In particular, jumping on a springboard 'in
      phase' and 'in antiphase' to relearn phase relations of oscillator coupling can
      be understood in the Haken-Kelso-Bunz 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. In conclusion, movement patterns relearned by oscillator
      formation training evolve from reorganization, and perhaps regeneration, of the
      lesioned CNS by cooperative and competitive interplay between intrinsic
      coordination dynamics, extrinsic training-related inputs with physiologic re
      afferent input, including intention and supervised learning, and genetic
      constraints including neurogenesis.

PMID- 10959250
TI  - Domenico Battini and his description of congenital megacolon: a detailed case
      report one century before Hirschsprung.
AB  - More than one century after the epochal paper of Harald Hirschsprung, and in
      spite of fast and remarkable advances in the pathophysiology of congenital
      megacolon, our understanding of how bowels may become functionally obstructed,
      and especially its variability, remains largely incomplete. While much more needs
      to be known about normal gastrointestinal physiology, an interaction between
      genetic and environmental factors seems to be of paramount importance in the
      pathogenesis of Hirschsprung's disease. While reviewing the relevant literature,
      we came across a virtually unknown contribution by an Italian physician, Domenico
      Battini, who happened to follow-up for about 10 years a case of severe
      constipation. This contribution, published posthumously as a book in 1800, not
      only describes very carefully the clinical evolution of that patient, but also
      provides a detailed post-mortem examination of the abdominal viscera, with
      particular reference to the alterations occurred in the intestines. We conclude
      that Battini, nearly one century before Hirschsprung, had succeeded in reporting
      a typical case of congenital megacolon, and had perceived a number of features
      (familiarity, selective involvement of "neural layers" in the gut mucosa) that
      were to become characteristic of Hirschsprung's disease a few decades after
      Hirschsprung himself had published his article.

PMID- 10959249
TI  - Behavioral disturbances and vestibular pathology following crotonitrile exposure
      in rats.
AB  - The dinitrile compound 3,3'-iminodipropionitrile causes a number of toxic effects
      in sensory systems, including degeneration of the vestibular sensory hair cells,
      as well as a neurofilamentous pathology in motor and sensory neurons. The
      chemical also causes permanent changes in behavior. These were initially
      attributed to the effect on neurofilaments, but have been recently linked to the
      vestibular toxicity. The present work studied the behavioral and pathological
      effects of the mononitrile compound crotonitrile. Adult male Long-Evans rats (n =
      8/group) were exposed to crotonitrile (0, 100, 125, 150 mg/kg/day, for 3 days,
      i.p., in 1 ml/kg corn oil) and assessed for changes in rearing activity,
      locomotor activity, and rating scores in tests of vestibular function. Surface
      preparations of the vestibular sensory epithelia were observed for hair cell loss
      by scanning electron microscopy (n = 3/group). Control (n = 2) and 3 x 150 mg/kg
      crotonitrile (n = 3) rats were assessed for neurofilament accumulation in
      vestibular and dorsal root ganglion neurons by light microscopy observation of
      semi-thin sections from plastic-embedded ganglia. Crotonitrile dose-dependently
      increased locomotor activity and rating scores for vestibular dysfunction. A dose
      dependent loss of vestibular hair cells was observed in the same animals. In
      contrast, no obvious neurofilament accumulations were observed in vestibular and
      dorsal root neurons. We conclude that vestibular toxicity is a property of the
      nitrile group, and that behavioral disturbances ensue from this toxic action.

PMID- 10959251
TI  - Differential in vitro modulation of Schwann cell proliferation by Mycobacterium
      leprae and macrophages in the murine strains, Swiss white and C57Bl/6.
AB  - The special susceptibility of Schwann cells (SCs) to parasitization by M. leprae
      and of macrophages to M. leprae-induced defects implicates them in leprous nerve
      pathogenesis. SC proliferation is an important prerequisite for peripheral nerve
      regeneration and is regulated by a number of secretory factors. Several of these
      factors are secreted by SCs themselves as well as by the macrophages which are
      recruited at the site of lesion to assist in regeneration. SC proliferation, as
      indicated by 3H-thymidine incorporation, was therefore studied in response to M.
      leprae infection and in the presence of macrophages in order to determine the
      role of SC in leprous neuropathy. Cells derived from two strains of mice, Swiss
      White (SW) and C57Bl/6 were used, as macrophages from these strains have been
      shown to differ in their response to M. leprae; such differences are similar to
      those observed in macrophages from lepromatous and tuberculoid leprosy patients,
      respectively. Infection with M. leprae for a duration of 9 days resulted in
      reduced proliferation of SCs from SW strain, while SCs from C57Bl/6 remained
      unaffected. However, in the presence of macrophages, SCs from both strains not
      only showed enhanced proliferation, but SW SCs also overcame the M. leprae
      induced suppression of their proliferation. Altered SC proliferation, therefore,
      can be implicated as a factor in leprous nerve pathogenesis. The strain variation
      observed in the response of SCs indicate different nerve damage mechanisms in
      lepromatous and tuberculoid patients.

PMID- 10959252
TI  - Correction of nerve conduction and endoneurial blood flow deficits by the aldose
      reductase inhibitor, tolrestat, in diabetic rats.
AB  - Increased activation of the first half of the polyol pathway, the conversion of
      glucose to sorbitol by aldose reductase, has been implicated in aldose reductase
      inhibitor-preventable neurochemical changes that may contribute to the aetiology
      of diabetic neuropathy. Tolrestat has been used as a standard aldose reductase
      inhibitor to dissect out polyol pathway-dependent mechanisms in many experimental
      studies; however, doubt has been cast upon its ability to prevent nerve
      conduction velocity deficits in diabetic rats. Nerve dysfunction has also been
      linked to abnormal endoneurial blood flow and oxygenation via increased vasa
      nervorum polyol pathway flux. The aim of this study was to test whether tolrestat
      could correct sciatic conduction velocity and perfusion defects in diabetic rats.
      Sciatic motor conduction velocity, 21% reduced by 1 month of streptozotocin
      induced diabetes, was corrected by 23% and 84% with 1 month of tolrestat
      treatment at doses of 7 and 35 mg/kg/day respectively. Endoneurial blood flow, 44
      52% reduced by untreated diabetes, was within the nondiabetic range with high
      dose tolrestat treatment and the flow deficit was 39% corrected by the low dose.
      Sciatic sorbitol and fructose concentrations were approximately 13-fold and
      approximately 4-fold elevated by untreated diabetes. This was 32-50% attenuated
      by low-dose tolrestat and sorbitol and fructose content was suppressed below the
      nondiabetic level by high dose treatment. A 58% nerve myo-inositol deficit was
      partially (32%) corrected by high-dose tolrestat treatment. We conclude that
      tolrestat restores defective conduction and blood flow in diabetic rats and is a
      good pharmacological tool for studies on polyol pathway effects in peripheral
      nerve.

PMID- 10959253
TI  - Errors in diagnosis of polyneuropathy: three cases of chronic lumbosacral root
      impairment.
AB  - In the last years very precise diagnostic investigations have been introduced to
      allow accurate diagnosis of pathologies affecting the major part of peripheral
      nerves; nevertheless, some avoidable misdiagnosis still occurs. For instance, the
      neurophysiological pattern observed in chronic compression of nerve roots may
      mimic an axonal polyneuropathy, especially when compression occurs in post
      ganglionic tract of dorsal root (in this case sensory nerve conduction studies
      show decreased or absent response). A clinical-neurophysiological dissociation
      may be noted in cases with pre-ganglionic impairment of dorsal root (clinical
      sensory deficit in presence of normal amplitude of sensory response). During the
      past two years we observed 3 cases with diagnosis of polyneuropathy that, after
      further studies, appeared affected by severe chronic compression of lumbo-sacral
      nerve roots. Our data suggest that in those cases with suspected polyneuropathy,
      in which the neurophysiological picture is characterized by the exclusive axonal
      (and myelinic) involvement of motor and/or sensory peripheral nerve of lower
      limbs, neuroimaging of radicular structures must be performed. These further
      investigations may avoid severe and irreversible damage to neural tissues.

PMID- 10959254
TI  - Treatment with acetyl-L-carnitine has the potential to improve the clinical
      course of painful peripheral neuropathies in HIV-positives patients.

PMID- 10959255
TI  - Extraneocortical origin of the neocortical neurons.
AB  - Recent studies have showed that although the most of the neocortical neurons are
      generated in the VZ and SVZ of the dorsal telencephalon, the ganglionic
      eminences, particularly the lateral ganglionic eminence contribute neurons to the
      neocortex. Most of these neurons migrate tangentially.

PMID- 10959256
TI  - Ependymal cells and astrocytes generate neurons.
AB  - Recent studies have showed that the ependymal cells and subventricular zone
      astrocytes are neurosphere-initiating cells and are neural stem cells. They give
      rise to neurons and glial cells in response to injury and utilization of
      endogenous stem cells in the treatment of nervous system diseases is important
      strategy in neurogenesis.

PMID- 10959257
TI  - Tangential migration of neurons during the development of the cerebral neocortex.
AB  - Two forms of neuronal migration have been described in the developing brain:
      radial migration in which young neurons climb on the shafts of radial glial
      cells, and tangential migration, in which cells move parallel to the surface of
      the ventricles and perpendicular to radial glia. The tangential migration occurs
      in multiple regions of the central nervous system. The relative prevalence of
      tangential versus radial migration has been estimated to be between 10% to 70%,
      depending perhaps on the regions of the central nervous system, the time of
      migration, and animal species studied.

PMID- 10959258
TI  - Sources and chain migration of neurons to the olfactory bulb.
AB  - Basing on literature the sources and migration of the olfactory bulb progenitors
      are described. These progenitors originate in the 1) ventricular zone, 2)
      subventricular zone, 3) lateral ganglionic eminence, 4) hippocampus, 5) ependymal
      cells, and 6) subventricular zone astrocytes. Neurons migrate tangentially in the
      rostral migratory stream. This type of migration is called the chain migration.

PMID- 10959259
TI  - The basolateral amygdaloid complex--its development, morphology and functions.
AB  - For many years the amygdaloid body has been an object of numerous investigations
      on different species, because the basolateral complex, being the main part of the
      amygdaloid body, is regarded as "sensory input" to this structure. It plays a
      very important role in so called emotional memory and learning, what is
      particularly important in early developmental stages. Impairment at this time may
      cause psychiatric problems in later life, like neurosis, phobia, unconscious fear
      or panic attacks. Complicated functions of the basolateral complex require
      precise control and modulation especially in early development. In this review
      the morphological changes during the development and maturation will be discussed
      and compared with neurotransmitter as well as with the expression of the calcium
      binding proteins at various stages of the development.

PMID- 10959260
TI  - Recent advances in neonatal pain research.
AB  - Pain accompanies most of illnesses. Pain results in from activation of a specific
      sensory system and is not direct result of an illness. Pain system may be
      activated early in the fetal development before its projections will penetrate
      the frontal cortex. Therefore, painful experience may induce some physiological
      consequences even it has been not perceived as pain and may lead to the long
      lasting and profound consequences. Noxious stimuli applied in the developmental
      period may exert dramatical effects upon growing children. Human infants and
      neonatal rats demonstrate hyperresponsivity to nociceptive input that may result
      in hyperalgesia. After birth, peripheral cutaneous innervation, neuroendocrine
      functions and mechanisms of inflammation still undergo developmental changes. The
      neurotransmitters of the inhibitory descending system (5HT, NE, DA) develop late
      or postnatally. Progress in research on the developmental aspects of nociceptive
      transmission is necessary basis for advances in pharmacology of pain and
      analgesia for fetuses in the last trimester, preterm and term neonates.

PMID- 10959261
TI  - Multipotent stem cells in the adult mammalian central nervous system.
AB  - The neural stem cells are primary precursors that can self-renew and generate
      differentiated neurons and glia. Such cells were cultured from adult nervous
      system. They were identified in the subventricular zone, hippocampus, spinal
      cord, ependyma and even were cultured from astrocytes. These cells are key
      players in the formation of the nervous system during development and they hold
      important clues for brain repair.

PMID- 10959262
TI  - Synaptogenesis and structure of the autonomic ganglia.
AB  - The present study summarises the current data dealing with processes leading to
      the establishing of the synaptic architecture and connections with both the
      preganglionic neurons and target tissues of autonomic ganglia Starting from the
      migration point of the neural crest cells, the factors and mechanisms driving the
      development of the autonomic nervous system, axonal pathfinding and establishing
      of ganglionic connections, as well as formation and plasticity of autonomic
      synapses are reviewed with regard to their functional relevance in these
      processes. Furthermore, the chemical neuroanatomy and somatotopic arrangement of
      either the preganglionic, sympathetic or parasympathetic division of the
      autonomic nervous system are discussed from the morphological ?and functional
      point of view.

PMID- 10959263
TI  - Differentiation, maturation, and function of Schwann cells (lemmocytes).
AB  - Schwann cells are a key regulators of peripheral nerve development, being
      required for the survival of neurons, the distribution of ion channels along
      nerve fibers and formation of myelin sheath as well as stimulation of development
      of the connective tissue sheath. They develop from the neural crest and
      differentiate into myelin- and non-myelin-forming cells.

PMID- 10959264
TI  - [The Israeli pharmaceutical market].
AB  - The pharmaceutical market in Israel has undergone many major changes over the
      past 2 years. We detail measures taken with regard to drug prices and
      utilization, from 1992 until 1995, when the National Health Insurance Law was
      implemented. This provides an information base for marketing and dispensing of
      drugs, economic planning in the public health system, and for physicians and
      pharmacists in clinical practice. The national expenditure on pharmaceuticals in
      1994 was 9.4% of the annual national health expenditure. From this fact, and the
      number of registered drugs and the number of clinical trials conducted, it
      appears that our pharmaceutical market is quite diversified and well developed
      compared to other markets in the western world. This size advantage enables our
      sick funds to purchase drugs at much lower prices than the private sector.

PMID- 10959265
TI  - [EBV-related lymphoproliferative disorder after liver transplantation].
AB  - We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative
      disorder was diagnosed 1 year after liver transplantation. She ran a complicated
      course with multiple organ involvement: respiratory failure which required
      mechanical ventilation, renal failure, bone marrow depression and severe protein
      losing enteropathy.

PMID- 10959266
TI  - [Severe heat stroke in an intensive care unit: course of the disease in the
      intensive care unit, and early and subsequent treatment results].
AB  - During the August 1998 heat wave in Tel Aviv we admitted many patients for acute
      heat-related illness; 6 had severe heat stroke and were admitted in critical
      condition. We describe their clinical courses during the first 5 days of
      hospitalization, including response to treatment and implications for future
      management of this disorder. The mean APACHE II score of the 6 was 30 +/- 3.5 and
      mean Glasgow Coma Scale rating 3.5 +/- 0.5; they were in hypovolemic shock and
      respiratory failure, necessitating mechanical ventilation. Despite early
      effective therapy (core temperature in all was reduced to less than 39 degrees C
      in less than 1 hour), there was 1 death (mortality 15%) and 4 required further
      intensive care for life-threatening multiple organ failure. During severe heat
      waves a significant number of referrals for acute heat-related illness must be
      anticipated, possibly overwhelming admission capacity of regional intensive-care
      units. Severe heat stroke complicated by multi-organ failure is not necessarily
      related to prior physical activity. Although important in determining prognosis,
      early treatment does not prevent severe complications. Mechanisms regulating body
      heat may remain disturbed for days following early treatment and apparent
      stabilization, mandating continued hospitalization.

PMID- 10959267
TI  - [The new family physician in the clinic].
AB  - The content of all consultations of a family physician during the first 2 months
      in a new practice and again in the same 2 months, 2 years later were analyzed.
      The workload did not change between the 2 periods, but in the first period there
      were relatively more men over the age of 60 years, and a more marked predominance
      of women in the 45-59 year age-group. There were more follow-ups of pre-existing
      conditions during the first period, but in both periods the main reason for
      visits was an acute condition; a quarter of visits required only simple
      counseling without further investigation or prescribing of medication. During the
      first period 9% of visits were for the explicit purpose of getting to know the
      new physician, usually by women. Thus the initial period in a new practice is not
      excessively burdensome, but involves seeing a number of patients who come either
      simply to get to know the new doctor, or to present non-chronic problems without
      expectation of further investigation.

PMID- 10959268
TI  - [Prevalence of medical complaints in the community-dwelling elderly receiving
      regular medication].
AB  - We assessed the prevalence of self-reported medical complaints among the
      community-dwelling elderly receiving regular medication, and determined
      associations between health and sociodemographic variables, and the prevalence of
      complaints. The study included 170 patients, 60-90 years of age, living at home.
      Participants were recruited from the 3 main primary care clinics in Rishon
      LeZion. All were receiving chronic medication and were followed-up utilizing a
      long-term medication card. Data were gathered in interviews held in patients'
      homes using a structured questionnaire which included sociodemographics, diseases
      and medication, mental state assessment by Katzman's score, and a list of 15
      medical complaints common among the aged. Relations to age, gender, education,
      living arrangements, number of diseases and number of medications per patient
      were determined. Mean age of participants was 73.2 +/- 6.0 years and they
      suffered an average of 4.07 +/- 2.16 diseases and took 5.10 +/- 2.83 types of
      drugs. The most prevalent complaints were: weakness and fatigue (65.0%),
      agitation and restlessness (56.4%), dry mouth (45.6%), constipation (43.6%) and
      dizziness (43.2%). The number of diseases, gender, education and age had the
      strongest associations with the prevalence of specific complaints, as well as
      their total number. The association between number of medications and mean number
      of complaints was of borderline significance.

PMID- 10959269
TI  - [Is there justification for limited percutaneous surgical drainage in severe
      neonatal necrotizing enterocolitis in low birth weight premature infants?].
AB  - The usual treatment of complicated neonatal necrotizing enterocolitis (NEC) is
      resection of the necrotic bowel, lavage of the peritoneal cavity and diversion
      enterostomy. Low-birth-weight premature neonates with this condition are in
      special danger if general anesthesia and full exploratory surgery is
      contemplated. A relatively simple alternate procedure is percutaneous insertion
      under local anesthesia of a soft abdominal drain, most often in the right lower
      quadrant. The procedure is done in the neonatal intensive care unit without
      moving the whole set-up to the operating room. 4 such cases have been treated
      within the past year. 3 were discharged home as they did not require additional
      surgical treatment, not having developed intestinal stenosis or obstruction. 1
      recovered from the acute episode, but succumbed to a severe intraventricular
      hemorrhage and respiratory failure 7 days after the procedure. Our limited but
      most gratifying experience, in addition to similar experience of others,
      encourages us to recommend this simple surgical approach in the very sick low
      birth-weight premature with fulminant NEC.

PMID- 10959270
TI  - [Neuropsychiatric side effects of malarial prophylaxis with mefloquine (Lariam)].
AB  - There has been an increased incidence of malaria among Europeans returning from
      Africa and Asia. The relatively new antimalarial mefloquine (Lariam) has become
      extremely popular due to its efficacy in treating the wide-spread chloroquine
      resistant Plasmodium falciparum. Mefloquine is used both for prophylaxis and
      treatment of malaria and is relatively well tolerated. However, since introduced
      in 1985, there have been over 100 reports of severe neurologic and psychiatric
      adverse effects associated with its use, including acute psychosis, affective
      disorders, acute confusional states and seizures. We describe a 39-year-old woman
      who developed acute psychosis after being given mefloquine prophylaxis. Adverse
      effects occur more often after therapeutic rather than prophylactic use, and
      those with a history of seizures or psychiatric illness are at increased risk of
      developing these reactions. Physicians should be aware of these possible side
      effects and prescribe mefloquine only when indicated.

PMID- 10959272
TI  - [Sonographic demonstration of a levonorgestrel-releasing IUD (Mirena)].
AB  - Mirena, a new intra-uterine device (IUD) introduced in Israel during the past
      year, releases 20 mcg/day of levonorgestrel for 5 years. It has the advantages of
      reduced pregnancy rates and diminished menstrual blood loss, together with a low
      risk of pelvic inflammatory disease compared with current IUD's. It has a typical
      sonographic appearance, differing from that of regular IUD's, which was
      demonstrated in all 15 women examined in this study. Its sonographic appearance
      includes both proximal and distal ends of the vertical arm of the device, which
      extend into the internal cervical os and fundal region, respectively. Acoustic
      shadowing between both ends defines the location of the device, which should help
      avoid consultations due to "lost IUD's."

PMID- 10959271
TI  - [Mesalamine-induced hypersensitivity pneumonitis].
AB  - A 23-year-old woman was admitted with a history of 2 weeks of cough, fever and
      bilateral lung infiltrates. She had been diagnosed 2 months before as having
      ulcerative proctitis and was treated with mesalamine, which induced a full
      remission, but 3 antibiotic regimens failed to improve her lung disease. Since
      computerized tomography revealed bilateral peripheral lung infiltrates and her
      eosinophile count was elevated, the diagnosis of drug-induced eosinophilic
      pneumonia was suggested. Mesalamine and antibiotics were stopped and oral
      corticosteroids begun. She became almost asymptomatic a week after mesalamine
      withdrawal, and the x-ray became normal.

PMID- 10959273
TI  - [Long life and quality of life].

PMID- 10959274
TI  - [Abetalipoproteinemia].

PMID- 10959275
TI  - [Is it possible to predict and prevent primary biliary cirrhosis?].

PMID- 10959276
TI  - [The relationship between violence and psychopathology].

PMID- 10959277
TI  - [Lowering intraocular pressure in glaucoma--by how much?].

PMID- 10959278
TI  - [Food and drug interactions].

PMID- 10959279
TI  - [Once a cesarean--always a cesarean?].

PMID- 10959280
TI  - [Clinical use of laboratory tests: methods for the selection of tests and for
      better perception of laboratory results].

PMID- 10959281
TI  - [Coping with psychiatric morbidity in primary care].

PMID- 10959282
TI  - [Lithotomy position during the second stage of delivery--is it worthwhile?].

PMID- 10959283
TI  - [Psychological aspects of ultrasound screening during pregnancy].

PMID- 10959284
TI  - [Basel cell carcinoma of the vulva].

PMID- 10959285
TI  - [Care of the geriatric and the demented patient--ethical and Halachic view].

PMID- 10959286
TI  - [Injuries due to falls in urban buses: 100 consecutive cases].
AB  - We reviewed the charts of 100 consecutive emergency department (ED) cases of
      injuries in public buses (not due to actual traffic accidents) seen during 7
      months in 1995. There were 29 males and 71 females with a mean age of 55.6 +/-
      21.4 years, median 60, and range 13-91. 92 were discharged home directly from the
      ED. 3 were admitted to general surgical wards, and 1 each to the orthopedic,
      medical and neurosurgical wards, while 2 soldiers were sent for observation to a
      military clinic. There were 28 spinal column, 27 head and 25 chest injuries; 1
      patient died. There were no significant differences in admissions during the
      months of the year. 58% of injuries occurred during normal working hours, with a
      peak incidence at about 1000 hrs. The most common cause was falling while
      standing, due to sudden acceleration/deceleration or sharp turns. There are 1900
      buses in Tel Aviv which carry 1.1 million passengers daily and most of which are
      capable of significant acceleration. A high proportion of passengers travel
      standing, and elderly passengers are more liable to fall when the bus
      accelerates, decelerates or turns. We calculate a potential national yearly bus
      injury toll from falls of more than 1000, which often result in significant
      morbidity and even mortality. A national survey is now being planned.

PMID- 10959287
TI  - [Professor Ludwig Guttman (1899-1980)].

PMID- 10959288
TI  - [Kurt Huldschinsky (1883-1940)].

PMID- 10959289
TI  - [Youth delegations to the concentration camps in Poland: local hospitals].

PMID- 10959291
TI  - [Measuring residual urine by portable ultrasound scanner].
AB  - Urethral catheterization, the standard method of measuring residual urine, is
      uncomfortable and associated with risk of infection and trauma to the urethra. It
      has also been reported as inaccurate to a certain extent. We compared
      catheterization with ultrasound scanning in a prospective study of 52 men and 3
      women. 100 measurements of postvoiding residual urine by portable ultrasound
      scanner, were each followed immediately by urethral catheterization (both
      procedures performed by an experienced nurse in our outpatient clinic). A
      difference of > 25 ml between measurements by scanner and by catheter was
      considered significant. The range of residual urine measured by scanner was 1-425
      ml, and by catheter 1-410 ml. There was good matching between the 2 methods in 85
      of 100 measurements (scanning accuracy 85%). In 30/85 matching was excellent
      while in 55 cases the mean difference was 8.5 +/- 6.2 ml, range 1-24 ml. The
      accuracy of scanning was 85%; there was perfect matching between the 2 methods in
      30 cases. In the remaining 15 cases the mean difference was 41.8 +/- 13.6 ml
      (range 25-56). Each catheterization took 4-5 minutes and scanning 30 seconds.
      There were no complications after catheterization, but all reported discomfort
      and dysuria for 1-2 hours thereafter. Scanning was absolutely uneventful in all.
      The cost per catheterization, including medication, disposable materials and
      personnel time was approximately 80 NIS. Our 80-90 measurements of residual urine
      a month require annually about 80 hours and a budget of about NIS 80,000.
      Scanning requires only 8 hours, while the cost of the portable scanner is
      significantly less than NIS 80,000 and it can be used for more than a year. We
      conclude that measuring urine residual with the noninvasive scanner instead of by
      catheterization is easier, more accurate, and more cost-effective.

PMID- 10959290
TI  - [Multicenter community-based trial of amlodipine in hypertension in Israel].
AB  - The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was
      evaluated in a "real life" setting. This open non-comparative trial included 123
      men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood
      pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline
      measurements, 2 weeks apart. Eligible patients were given AML 5 mg daily as add
      on or monotherapy and were evaluated 4 weeks later. If DBP was then > 90 mmHg,
      the daily dose was raised to 10 mg; those with < 90 mmHg remained on 5 mg. AML
      was continued for 8 weeks. Other BP-lowering drugs were unchanged. Of the
      original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others
      were protocol violators, lost to follow-up or withdrew, leaving 211 available for
      efficacy analysis. In this major group BP was reduced from 165 +/- 15/101 +/- 4
      to 139 +/- 11/83 +/- 5 after 12 weeks of AML (p < 0.05). The reduction was
      greater in those under 70 years, from 173 +/- 12/100 +/- 5 to 142 +/- 12/80 +/- 4
      (p < 0.05). In those with BMI > 30 kg/m2, BP decreased from 165 +/- 15/101 +/- 5
      to 140 +/- 12/83 +/- 5 (p < 0.05). Mean change in heart rate was -1.5 bpm (p <
      0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE
      requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in
      3.7% it persisted during therapy. Other AE occurring in > 1% were dizziness in
      1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%. We conclude that AML is an
      effective and well-tolerated antihypertensive suitable for most hypertensive
      patients.

PMID- 10959292
TI  - [Violence in the emergency department].
AB  - There is an international epidemic of violence in the emergency department (ED)
      which threatens medical staff daily. The problem is underestimated in Israel and
      there are as yet no regulations of the Ministry of Health and the Bureau of
      Security and Safety that deal with the problem. At the beginning of 1997 we
      conducted a retrospective survey to estimate the extent of this problem and to
      define its causes and the various options for management. An anonymous
      questionnaire was given to all permanent workers of our ED: physicians, nurses
      and reception clerks, as well as physicians who worked in the ED during evening
      and night shifts at least twice a week. 74% of (questionnaire) responders
      experienced violent events, most of them 5 or more times during the previous 2
      years. Violence was experienced by 90% of nurses, 70% of physicians and 64% of
      clerks. The main reason for violence was prolonged waiting in the ED. Other
      causes were dissatisfaction with treatment, refusal to leave the ED, and language
      that displeased the patient. Most violent patients were middle-aged men, of whom
      alcohol and drug users were only a small proportion. Most victims of physical
      violence called hospital security personnel, but only a third of the victims of
      verbal violence pressed charges. Half of the staff who were physically attacked
      called the police and most pressed charges. Only 2 attackers were convicted;
      charges were dropped against 3 because of "lack of public concern." We were
      unable to ascertain the results of the other charges. Most victims of violence
      didn't press charges because of fear resulting from threats of the patient and/or
      family. The violent patient was usually characterized by responders as a middle
      aged man, sober, of low socioeconomic level, impatient, with a bad previous
      hospital experience, dissatisfied with treatment and who insisted on being
      admitted to hospital. Suggestions for violence management by questionnaire
      responders included 24-hour police protection and a training program in violence
      management for hospital security and medical staff.

PMID- 10959293
TI  - [Familial hemiplegic migraine of childhood].
AB  - Familial hemiplegic migraine is a rare autosomal, dominant, migraine subtype. It
      is characterized by acute episodes of hemiplegia and hemisensory deficits, and
      other neurological abnormalities occurring either before or together with severe
      headache, nausea and vomiting; episodes last several hours and then spontaneously
      subside. Intervals between episodes are relatively prolonged. Unless there is a
      relevant family history suggesting this syndrome, the diagnosis is usually
      delayed. Recently the gene for the syndrome was identified on chromosome 19. We
      report 3 boys and 1 girl, 11-15 years old with hemiplegic migraine.

PMID- 10959294
TI  - [Biofeedback treatment of irritable bowel syndrome].
AB  - Irritable bowel syndrome is a group of heterogenic complaints of functional bowel
      disorder in the absence of organic pathology. The pathophysiology is unclear. In
      most cases treatment includes symptomatic remedies, antidepressants,
      psychotherapy and hypnotherapy. Biofeedback has recently been introduced as a
      therapeutic modality. Treatment also includes relaxation techniques and guided
      imagery, together with computer-assisted monitoring of sympathetic arousal.
      Biofeedback requires active participation of patients in their healing progress
      and leads to symptom reduction in 2/3.

PMID- 10959295
TI  - [Severe hypercalcemia due to renal transitional cell carcinoma].
AB  - Hypercalcemia is a common metabolic disorder, especially in the elderly. The most
      common etiologies are hyperparathyroidism or malignancy, most often of the lung,
      breast, kidney or hematological system. Because hypercalcemia is an uncommon
      manifestation in urinary tract epithelial tumors, especially those of the renal
      pelvis, we present a man aged 62 years with hypercalcemia due to renal
      transitional cell carcinoma.

PMID- 10959296
TI  - [Multi-locational cystic mass of the kidney: a diagnostic challenge].
AB  - Multilocular cystic masses of the kidney present a diagnostic challenge because
      they may be malignant. Renal cell carcinoma with multilocular cysts has been
      reported. We present 4 cases in which the preoperative differential diagnosis was
      between a benign and a malignant multilocular cystic kidney mass. Our results,
      combined with those of 33 previously reported cases, reveal that only 32% of
      cases were diagnosed correctly preoperatively. In 21% of these patients the
      preoperative clinical evaluation did not correctly diagnose malignancy: 24% of
      them yielded false negative and 21% false positive results. Angiography was more
      accurate than CT, US or aspiration of cysts. Frozen section was inaccurate in 55%
      of cases. There is no reliable diagnostic test to distinguish between a malignant
      and a benign multilocular cystic mass. Invasive angiography is more accurate than
      other modalities. A therapeutic decision has to be made between nephron-sparing
      and radical surgery in each case. When nephron-sparing surgery is considered, the
      possible need to perform radical nephrectomy in second-look surgery must be taken
      into account.

PMID- 10959298
TI  - [Euthanasia: confronting death].

PMID- 10959297
TI  - [Severe transient neutropenia due to parvovirus B19].
AB  - A 10-year-old girl was admitted with a 3-day history of fever, cough, abdominal
      pain and vomiting. Severe neutropenia (total neutrophil count 186/mm3), a mild
      increase in ALT and AST, and a positive titer of IgM antibodies against
      parvovirus B19 were found. The neutropenia resolved and liver enzymes became
      normal as she recovered. We conclude that parvovirus B19 infection should be
      considered in the evaluation of an acute illness accompanied by severe
      neutropenia.

PMID- 10959299
TI  - [Euthanasia in historical context: autonomy and regulation].

PMID- 10959301
TI  - [The risk of venous thromboembolism in women during hormone replacement therapy].

PMID- 10959300
TI  - [Anti-cytokine therapy in inflammatory joint diseases].

PMID- 10959302
TI  - [Gliadel--a preparation for the supplementary treatment of brain cancer].

PMID- 10959303
TI  - [Use of lithium in hyperthyroidism].

PMID- 10959304
TI  - [Microvessel density--a prognostic factor in gynecological malignancies].

PMID- 10959305
TI  - [Neonatal diabetes].

PMID- 10959306
TI  - [Skeletal bone metastasis--current concepts of diagnosis and treatment].

PMID- 10959307
TI  - [Rehabilitation of demented patients after fractures and orthopedic surgery as a
      multi-professional and social problem].

PMID- 10959308
TI  - [Interactions between grapefruit juice and medications].

PMID- 10959310
TI  - [Relapsing polychondritis].

PMID- 10959309
TI  - [Possible association between serum C-reactive protein concentrations and
      ischemic heart disease].

PMID- 10959311
TI  - [The temples of Asclepius].

PMID- 10959312
TI  - [Selma Meyer (1881-1958)--the first woman professor of pediatrics in Germany].

PMID- 10959313
TI  - [Burns in children in Israel--epidemiology, prevention and treatment].
AB  - 45% of all hospitalized burn casualties in Israel are children younger than 16
      years old. In various hospitals they make up 30-60% of all burn casualties,
      depending on the proportion of children in the area of hospital intake, social
      and economic factors and the type of hospital. Length of hospitalization of
      children is shorter than that of the general population (7.3 vs 9.0 days).
      Scalding is the main cause of thermal injuries among babies and infants (70%),
      while fire burns are the most common causes among adolescents (56.5%); 90% of
      babies are injured at home; only 40% of adolescents are burned in home accidents.
      In Israel, burned children are treated in 25 different hospitals and in
      departments of pediatric surgery, plastic surgery, general surgery, pediatrics or
      burn departments. There is no pediatric burn unit in Israel.

PMID- 10959314
TI  - [Tension-free vaginal tape--a new surgical treatment of female urinary stress
      incontinence].
AB  - Female urinary stress incontinence diminishes the quality of life of about 5% of
      women. It is usually dealt with by surgery to correct the relaxed pelvic floor,
      the cause of the incontinence. Tension-free vaginal tape is used in a newly
      described procedure. It consists of the vaginal introduction of a prolene needle
      guided mid-urethral sling. The procedure is easy to perform under local
      anesthesia, recovery is rapid, and results are similar to those of other
      effective operations. We report 44 patients who underwent this type of surgery.
      There were no significant complications. The early results were good and although
      the follow-up has been short, we believe that experience with this operation will
      play an important role in the treatment of urinary stress incontinence.

PMID- 10959315
TI  - [Infective endocarditis presenting as polyarticular septic arthritis].
AB  - We report acute polyarthritis in an 86-year-old man which was initially
      considered to be an exacerbation of osteoarthritis. After a delay of a few days a
      diagnosis of septic polyarthritis as an initial symptom of infective endocarditis
      was made. Although rheumatic manifestations in infective endocarditis are common,
      septic polyarthritis is rarely seen. In our patient the course of the disease was
      rapidly fatal.

PMID- 10959316
TI  - [Clozapine in the treatment of schizophrenia].
AB  - Schizophrenia is associated with brain abnormalities and is typically evidenced
      by disorganized speech and behavior, delusions, and hallucinations; it usually
      requires extended hospitalization. Its incidence in the western world is
      estimated at 4-7 cases/10,000/year. A method of shortening hospitalization and
      improving level of functioning is the use of unique medication, including
      clozapine, which has been in use in Israel for the past 6 years. We report 327
      patients who participated in a community rehabilitation program and were treated
      with clozapine. They were compared with 417 patients who corresponded to the
      guidelines of the Director of Mental Health Services for treatment with
      clozapine, but were not treated with it for reasons not defined in the
      guidelines. The study included those 25-44 and 45-64 years of age and according
      to the division of the population of patients hospitalized in both government and
      private hospitals. The project demonstrates the savings from use of clozapine as
      opposed to the alternative of hospitalizing these patients. It also shows the
      complexity and difficulty in assimilating new technologies, in relation to the
      influence of social considerations and supplier/insurer accounting on the
      patterns of technological assimilation.

PMID- 10959317
TI  - [Severe pneumonia caused by Bordetella bronchiseptica].
AB  - Bordetella bronchiseptica rarely causes disease in man, and is an unusual
      pathogen in animals. It causes a pertussis-like syndrome, but pneumonia and
      sepsis have been described in the immunocompromised as well as in the
      immunocompetent. A 53-year-old man with adult-onset diabetes and healed pulmonary
      tuberculosis presented with lobar pneumonia and rapidly developed septic shock
      with adult respiratory distress syndrome. He responded well to the combination of
      piperacillin-tazobactam.

PMID- 10959318
TI  - [Plication of diaphragm for postoperative phrenic nerve injury in infants and
      young children].
AB  - Paralysis of the diaphragm may cause life-threatening respiratory distress in
      infants and young children because of paradoxical motion of the affected
      diaphragm and contralateral shift of the mediastinum during expiration. Phrenic
      nerve injury (PNI) may follow chest operations. 10 children with diaphragmatic
      paralysis and severe respiratory distress underwent plication of the diaphragm.
      Ages ranged from 14 days to 5 years. 9 had PNI after operations for congenital
      heart disease and 1 after resection of an intraspinal cervical lipoma. The right
      side was affected in 7, the left in 3. Indication for surgery was inability to
      wean from mechanical ventilation, which had ranged from 11 to 152 days (median
      35). 8 underwent plication via a thoracic approach and 2 via an abdominal
      approach. There were no complications directly related to the operation. The
      interval from plication to weaning from mechanical ventilation ranged from 2 to
      140 days (median 4). 1 patient died 2 hours after plication due to severe heart
      failure and 2 after prolonged hospitalization due to sepsis and multi-organ
      failure. 6 were extubated 2-8 days (median 4) after plication and 1 only after 40
      days. Early diaphragmatic plication is simple and avoids more serious surgery.
      While effective in ventilator-dependent infants and young children, it should not
      be used in those with multi-organ failure. Early plication may prevent the
      complications of prolonged mechanical ventilation.

PMID- 10959319
TI  - [When are menopausal symptoms psychiatric?].
AB  - Nervousness, sleep disorders, mood instability and sexual dysfunction are
      frequent symptoms during menopause. It is commonly believed that they are due to
      the characteristic menopausal hormonal changes. However, they also commonly occur
      in psychiatric disorders unrelated to the menopause. The literature deals with
      the characteristic psychological aspects and studies have examined the ways in
      which menopausal phenomena are related to the hormonal background and its effect
      on the brain. The clinical menopausal picture may be complicated by secondary
      psychiatric disease. Also, menopausal symptoms and symptoms of previous
      psychiatric disease may coexist. In addition, menopause may precipitate
      psychiatric disorders in women predisposed to them. Accumulated personal myths
      and expectations related to the menopause are likely to affect the way in which a
      woman copes with it. Important factors in this connection include education,
      culture and certain life events. In all such cases precise evaluation of the
      etiology, with its intermingled gynecological and psychiatric factors is
      required. Such women should be treated by both a gynecologist and a psychiatrist.
      We present 5 cases, 4 of which were sent to the menopause clinic and were then
      referred for psychiatric evaluation and treatment. The other case presented at a
      psychiatric clinic due to a first acute psychotic state. Laboratory tests showed
      typical changes of menopause.

PMID- 10959320
TI  - [Malignant eccrine poroma--a rare occurrence].
AB  - Malignant eccrine poroma (MEP) is rare and both clinical and histologic diagnosis
      is often difficult. Therefore, diagnosis is sometimes delayed or even incorrect.
      We report a case in a 70-year old man with MEP of the leg. He demonstrated
      typical MEP behavior and the problems of differential diagnosis.

PMID- 10959321
TI  - [Ferritin levels in adult Still's disease].
AB  - Adult-onset Still's disease (AOSD) is characterized by a spiking fever and
      diverse clinical findings; the diagnosis is often delayed for months or even
      years. The only positive laboratory finding is neutrophilic leukocytosis. Since
      1987, the diagnostic importance of elevated serum ferritin levels has been
      discussed in numerous papers, but is not yet among the diagnostic criteria for
      AOSD. We describe a case in which the finding of extreme hyperferritinemia
      enabled prompt diagnosis and treatment.

PMID- 10959322
TI  - [Equine Rhodococcus equi pneumonia: first report in Israel and its significance
      for man].
AB  - Rhodococcus equi is an important pathogen in young horses. In recent years it has
      been increasingly recognized as an opportunistic infectious agent in patients
      with immune deficiency. The increase in recognized cases may be related to the
      increased prevalence of AIDS. However, more cases may have been recognized lately
      due to increased awareness of the pathogenicity of this bacterium. Based on
      medical reports, there appears to be an association between Rhodococcus equi
      infections and exposure to animals, horses in particular. During the past year, 2
      cases of rhodococcus pneumonia were diagnosed in foals in Israel. This
      information deserves the attention of the local medical community because of the
      zoonotic potential of Rhodococcus equi and the danger of its becoming more
      common. The climate in Israel is conducive to its growth and viability and since
      it flourishes in an environment with horses, the significant growth in our equine
      industry in recent years may contribute to an increase in Rhodococcus infections.

PMID- 10959323
TI  - [Antibiotics in upper respiratory tract infections in children].

PMID- 10959324
TI  - [Oxidants and antioxidants and the clinical importance of ischemia reperfusion
      injury].

PMID- 10959325
TI  - ["Gulf War syndrome"--a typical postwar reaction?].

PMID- 10959326
TI  - [Assessment of fetal well-being by measuring cerebral artery blood flow].

PMID- 10959327
TI  - [Low molecular weight heparin in acute coronary syndromes].

PMID- 10959328
TI  - [Cardiac rehabilitation for women: need and availability].

PMID- 10959329
TI  - ["Phantom breast"].

PMID- 10959330
TI  - [Clinical significance of antibiotic treatment in women with preterm premature
      rupture of membranes].

PMID- 10959331
TI  - [Physical exercise and juvenile arthritis--update].

PMID- 10959332
TI  - [Gadolinium during pregnancy].

PMID- 10959334
TI  - [Risk factors and the prevention of alcohol-related problems among adult women-
      the young, the adult and the elderly].

PMID- 10959333
TI  - [Septic encephalopathy].

PMID- 10959335
TI  - [On Moliere, Alterman and Dr. Shaul Tchernichowski].

PMID- 10959336
TI  - [PVT--tension-free vaginal tape--a new minimally invasive surgical technique for
      female stress incontinence: preliminary results].
AB  - We evaluated the safety and efficacy of the tension-free vaginal tape procedure
      (TVT) in 20 consecutive women with urodynamically proven genuine stress
      incontinence. Mean operating time under spinal analgesia was 37.2 +/- 13 minutes
      and 80% were discharged within 24 hours. There were 5 uncomplicated,
      intraoperative bladder perforations, but no defects in healing nor tape
      rejection. The objective cure rate was 95%, while the subjective rate was 100%.
      Although follow-up was short (9-16 months), the TVT method seems to be safe and
      effective for stress urinary incontinence.

PMID- 10959337
TI  - [Listeria monocytogenes infections--ten years' experience].
AB  - 7 cases of listeriosis were diagnosed here between 1988-1997 (6 in last 3 years),
      or 2.94/100,000 admissions. 2 elderly patients suffered from meningitis and 2
      pregnant women presented with premature contractions, 1 of whom delivered a
      premature, infected baby. 2 other patients had fever and gastroenteritis.
      Listeria monocytogenes was isolated from blood in 4, CSF in 2 and the placenta in
      1. It was isolated from those with bacterial meningitis. All patients recovered.
      Both increased awareness for prevention and better diagnosis are essential to
      reduce morbidity from this unusual pathogen.

PMID- 10959338
TI  - [Photodynamic therapy for dysphagia due to esophageal carcinoma].
AB  - Surgery is the mainstay in the treatment of esophageal carcinoma and is effective
      for palliation of dysphagia. Patients unfit for surgery are difficult therapeutic
      problems. We evaluated photodynamic therapy for palliation of dysphagia in this
      condition. Patients were given 5-aminolevulinic acid, 60 mg/kg, orally and 24
      hour later gastroscopy was performed during which red light illumination (100
      j/cm2 for 600 seconds) was administered. This was repeated 48 hours later. The
      degree of dysphagia was recorded before and 14 days after treatment. 8 patients
      with an advanced non-resectable tumor, or who were unfit for surgery, were thus
      treated. 4 had squamous cell carcinoma of the mid-esophagus and 4 had
      adenocarcinoma of the lower esophagus. There was mild, self-limited
      photosensitivity in all. Liver and renal function tests and blood count were not
      affected by the treatment. Dysphagia was improved in all except 1 patient. A
      patient with early stage disease continued to eat a normal diet. We believe that
      photodynamic therapy with systemic aminolevulinic acid as a photosensitizer and a
      non-laser light source is feasible and safe in advanced esophageal cancer. It is
      an effective modality for relief of dysphagia in that condition.

PMID- 10959339
TI  - [Apomorphine for treatment of "off-periods" in Parkinson's disease].
AB  - After 3-5 years of continuous use of 1-dopa preparations for Parkinson's disease,
      25%-50% of patients develop side-effects such as the "on-off" phenomenon and
      involuntary movements that markedly impair function. One cause of these
      manifestations is evidently a disturbance in the absorption of 1-dopa. We
      attempted to avoid this problem by using subcutaneous injections. Apomorphine is
      a rapid-acting dopamine agonist which causes a return from "off" to "on" within
      minutes. We present the results of a trial of subcutaneous injections of
      apomorphine in 22 Parkinsonian patients (12 males, 10 females) with severe motor
      fluctuations. During 5 days prior to the apomorphine all received Motilium
      (domperidone, 60 mg/d) to prevent nausea and vomiting. All were hospitalized
      initially to determine optimal dosage and to teach them the technique of self
      injection. 2 to 4 mg of apomorphine were injected 1 to 3 times daily for 2 to 12
      months. In 17 patients (80%) "off" periods were reduced without significant side
      effects. Apomorphine seems to be effective, tolerable treatment for shortening 1
      dopa induced "off" periods.

PMID- 10959341
TI  - [Follicular splenic lymphoid hyperplasia associated with EBV infection].
AB  - Massive splenomegaly is defined as a spleen weighing about 10 times normal
      weight. We describe a 36-year-old man who had huge splenomegaly and secondary
      pancytopenia simulating malignant lymphoma for about 3 months. Splenectomy was
      necessary because of the suspicion of hematologic malignancy, especially isolated
      lymphoma of the spleen, and pain and mechanical abdominal disturbances. On
      operation, the spleen was 25 cm long and weighted 250 g. There was florid,
      reactive follicular lymphoid hyperplasia. Immunohistochemical staining with CD
      20(L26), CD-45Ro(UCHL), bcl-2 oncoprotein (Dakopatts), EBV (anti-EBV mol weight
      60 KD, Dakopatts) was consistent with reaction to EBV infection and not with
      follicular lymphoma. Lack of PCR amplification using DNA extracted from paraffin
      embedded splenic tissue indicated absence of a monoclonal B cell population
      carrying rearranged immunoglobulin genes. The lymphocytic population was proven
      polyclonal by the negative results of PCR for the bcl-2 gene rearrangement. EBV
      seroconversion from high titer antibodies of anti-EBV-VCA-IgM to negative, and
      from negative EBNA to positive was consistent with an apparent primary EBV
      infection. We have not found on computerized search a previous report of reactive
      follicular splenic hyperplasia to EBV infection causing huge splenomegaly, with
      or without EBV-induced infectious mononucleosis.

PMID- 10959340
TI  - [Can police car flashing lights induce a risk of encephalographic epileptic
      discharges and seizures?].
AB  - The new police car flashing-light device (930 Heliobe Lightbar) has recently been
      implicated as potentially epileptogenic. We exposed 30 epileptic patients, 30
      nonepileptic patients who suffered from headache and 15 normal volunteers to this
      light source. All had routine EEGs with standard intermittent photic stimulation,
      followed by 3-minute stimulation with the Lightbar. In none were either seizures
      or EEG changes induced. In 1 epileptic spike-and-wave activity induced by
      standard photic stimulation was enhanced with the Lightbar. We could not confirm
      that the Lightbar is epileptogenic.

PMID- 10959343
TI  - [Control of brucellosis in Taibe: multi-central collaboration].
AB  - Brucellosis is contracted from domestic animals. Poor hygiene, primitive animal
      breeding methods and traditional food preparation are the main contributory
      factors. We describe an intersectoral program for controlling brucellosis in
      Taibe, an Arab town in Israel, which had a particularly high incidence of the
      disease in 1992 and 1993. At the beginning of 1994 the Israel Ministry of Health
      and the Community Pediatric Center of Taibe established a community-based program
      for controlling brucellosis in Taibe. It included an intensive public health
      education campaign and periodic examination and vaccination of animals.
      Physicians, veterinarians, nurses, school officials and health inspectors were
      recruited for this purpose. Residents' awareness of brucellosis was determined
      before and after the study. After intervention, the incidence of the disease
      sharply declined from 176.6 and 175.0/100,000 in 1992 and 1993 respectively, to
      5.7, 10.4 and 2.5/100,000 in 1994, 1995 and 1996, respectively, (odds-ratio
      24.44; p < 00000). Residents' awareness of brucellosis and preventive measures
      were significantly increased by the end of the study. We conclude that
      intersectoral collaboration is an important tool for controlling brucellosis.

PMID- 10959342
TI  - [Alpha-amino adipic aciduria: a rare psychomotor syndrome].
AB  - A 3.5-year-old boy with developmental motor retardation, hypotonicity, and severe
      speech disturbance had alpha-amino adipic acid in his blood and very high levels
      in his urine. In only 20 cases has this catabolite of lysine and hydroxylysine
      been found in high concentrations in urine, due to enzymatic block. The clinical
      features associated with alpha-amino adipic aciduria may include mental
      retardation, developmental and motor delay, learning difficulties, convulsions,
      speech problems and ataxia. 3 siblings had milder symptoms of psychomotor delay
      and intermediate degrees of alpha amino-adipic aciduria, suggesting that the
      described developmental deficits could be related to this metabolite or its
      derivatives.

PMID- 10959344
TI  - [Congenital syphilis: need for adequate antenatal care].
AB  - Congenital syphilis is well-known and treatable with penicillin. Diagnosis in the
      neonate and young child may be difficult and consequently morbidity and mortality
      can be high. Prevention in children is of utmost importance and can be achieved
      by proper antenatal care and adequate follow-up of pregnant women. This includes
      identification of pregnant women at risk for contracting syphilis. The case
      presented demonstrates this need.

PMID- 10959345
TI  - [Choreoathetosis after cardiac surgery in children].

PMID- 10959346
TI  - [Surfactant replacement therapy in neonatal respiratory distress syndrome:
      prophylactic therapy versus treating of established disease].

PMID- 10959347
TI  - [Treatment of constitutional tall stature in boys and girls].

PMID- 10959348
TI  - [Spinal dural arteriovenous fistula].

PMID- 10959349
TI  - [To close or not to close the peritoneum in abdominal gynecologic and obstetric
      operations].

PMID- 10959350
TI  - [Hypokalemia induced by amphotericin B].

PMID- 10959351
TI  - [Glucocorticoid treatment in preterm birth].

PMID- 10959352
TI  - [Carbohydrate deficient glycoprotein syndromes].

PMID- 10959353
TI  - [Obesity in the elderly].

PMID- 10959354
TI  - [Trends in complementary medicine towards the third millennium].

PMID- 10959355
TI  - [Ethical obligations of physicians concerning alternative medicine].

PMID- 10959356
TI  - [Guardianship nomination: rethinking the decision making process].

PMID- 10959358
TI  - [Eduard Heinrich Henoch (1820-1920)].

PMID- 10959357
TI  - [William Carlos Williams: physician, poet, writer and playwright].

PMID- 10959359
TI  - [Aberrant teeth].

PMID- 10959360
TI  - [Thoracoscopic splanchnicectomy for intractable pancreatic pain].
AB  - Intractable pain is the most distressing symptom in nonresectable pancreatic
      carcinoma and in chronic pancreatitis. Recently, thoracoscopic splanchnicectomy
      has been advocated as a minimally invasive method of pain control in these
      patients. Between May 1995 and April 1998, 24 patients with nonresectable
      pancreatic cancer and 4 with chronic pancreatitis, underwent 43 thoracoscopic
      splanchnicectomies. All suffered from intractable pain, were opiate-dependent and
      unable to perform normal daily activities. Unilateral left splanchnicectomy was
      done in 13 and bilateral in 15. All procedures were completed thoracoscopically.
      Operative time ranged from 25 to 60 min and mean hospital stay was 3 days. Median
      pain intensity was reduced by 50% in 24 and no further narcotics or analgesics
      were required. We found thoracoscopic splanchnicectomy a safe and effective
      procedure for intractable pancreatic pain.

PMID- 10959361
TI  - [Thromboembolism in orthopedic trauma].
AB  - Trauma increases risk of thromboembolic complications. Thus, in pelvic fractures
      and spinal injuries the incidence of deep vein thrombosis (DVT) is about 35-60%.
      Half occur in the pelvic veins and are the most likely to result in pulmonary
      embolism. While symptomatic pulmonary embolism occurs in 2-10% of patients, more
      have silent pulmonary embolism. 0.5-2% of pulmonary embolisms are fatal. In lower
      extremity trauma the incidence of DVT is about 58%, with 18% of them in the
      proximal veins. Thromboembolic complications are the prime cause of morbidity and
      mortality among trauma patients, yet they can be prevented efficiently and cost
      effectively. The arsenal of prophylactic agents includes heparin, low molecular
      weight heparin, and mechanical devices including inferior vena cava filters.

PMID- 10959362
TI  - [Physiological aspects of women in combat].
AB  - Since military service is physically demanding, soldiers must maintain high
      levels of physical fitness for optimal performance of their duties. Women are at
      a physiological disadvantage when competing against men: they have a smaller
      muscle mass, more body fat, lower red blood cell counts, lower hemoglobin levels
      and smaller cardiac outputs. Women are slower and weaker than men and more prone
      to exercise-induced skeletal injuries. Fewer women than men meet the standards of
      physically demanding jobs. Therefore integrating women into physically demanding
      military-oriented jobs requires redesigning or modifying the tasks (different
      pace, mechanical aids, teamwork). While physical training can increase the
      physical capacity of women, training cannot completely eliminate gender
      differences. Thus the data presented do not imply that women cannot be integrated
      into combat units, but highlight gender-related differences which might have an
      effect on the ability of women to compete equally with men at the same task.

PMID- 10959363
TI  - [Laser treatment of airway obstruction in infants and children].
AB  - Airway obstruction during infancy and childhood requiring surgical ablation is
      rare, and surgical intervention poses a significant challenge. During recent
      decades, appropriate endoscopic instrumentation, together with advanced laser
      beam technology have provided new operative modalities for such patients. From
      1993 to 1995 we treated 40 infants and children, 26 males and 14 females, 13 days
      to 11 years old (mean 3.3 years) with Nd-YAG or CO2 laser. Obstructing lesions
      included granulation tissue or polyps (16 cases), septa or webs (27), or benign
      tumors (4). 7 had more than a single lesion. All were treated endoscopically
      under general anesthesia without any operative or postoperative deaths. Surgical
      intervention removed the obstruction and related symptoms in 34. In 6, laser
      treatment failed, necessitating additional surgical procedures. 3 had
      circumferential subglottic web. Operative complications included bleeding during
      removal of a hemangioma in 1 and recrudescence in another. Postoperative
      complications were transient respiratory failure and pneumonia in 6, all of which
      resolved with appropriate treatment. This series proves that laser technology is
      feasible in the treatment of airway obstruction during infancy and childhood, and
      is safe and effective.

PMID- 10959365
TI  - [Use of unlicensed and off-label drugs in hospitalized children].
AB  - Many drugs used in children are based on pharmacological data obtained in adults.
      Therefore, many drugs are either unlicensed for use in children or are prescribed
      outside the terms of the product license (off-label). This pilot study assessed
      use of unlicensed or off-label drugs in hospitalized children. Drug orders of
      patients admitted to a general pediatric ward were reviewed retrospectively in a
      random sample. Assessment was based on the data of the Physicians' Desk Reference
      and the Israel Drug Compendium. 80 different drugs and 278 drug orders were
      written for 92 patients (0.5 months-11 years old, mean 26.9 months) in 97
      admissions. Of these 52.9% were either off-label or unlicensed. Patients received
      1 or more unlicensed or off-label drugs in 64.9% of admissions. They were more
      often off-label than unlicensed. The main reasons for use of off-label drugs were
      unusual doses and inappropriate age. The main reason for unlicensed drugs was
      modification of a particular formulation of a licensed drug. This pilot study
      indicates that use of drugs in an off-label or unlicensed manner in children is
      probably quite frequent in Israel. Our data emphasize the need for licensing a
      large number of drugs for use in children, based on the same scientific
      principles as in adults. Further collaborative studies in different pediatric
      centers in Israel, involving different types of pediatric settings (ambulatory
      and in-hospital), is required to evaluate comprehensively the magnitude of this
      preliminary finding.

PMID- 10959364
TI  - [Extraperitoneal laparoscopic adrenalectomy].
AB  - Laparoscopic adrenalectomy has recently been shown to be safe and effective for a
      variety of benign adrenal tumors, such as aldosterone adenoma, pheochromocytoma,
      nonfunctioning adenoma, Cushing's adenoma and Cushing's syndrome. Recently,
      laparoscopic surgeons adopted an extraperitoneal approach in which a space is
      created by the introduction of a trocar with an inflatable balloon tip. This
      technique with a minimal access procedure provides direct access to the adrenal
      glands without interfering with intraperitoneal organs. Laparoscopic
      adrenalectomy using the extraperitoneal approach was completed in 18/20
      consecutive patients. Mean operative time was 95 min (range 80-120) and median
      hospital stay 3 days. Blood transfusion was not required, and there were no
      postoperative complications.

PMID- 10959366
TI  - [Sport-related maxillofacial fractures].
AB  - The records of 537 patients with 750 maxillofacial fractures were reviewed and
      analyzed. 55 (10.2%) had sport-related injuries and the rest were due to other
      causes. The sport-related group was predominantly male (ratio 9:1) with a mean
      age of 24.5 years. The mandible was most commonly injured (52.5%), followed by
      the zygomatic complex (32.8%). The incidence of complicated mid-facial fractures
      was only 2.8%, and of comminuted fractures 9%. This distribution of injuries is
      most likely due to the relatively low-energy of trauma associated with many sport
      activities. The relatively low mean age of the patients, most of whom had full
      dentition, allowed for conservative treatment of most of the mandibular
      fractures, using closed reduction. Injuries were caused by 11 different sports.
      The highest incidence was soccer (45%), followed by skating (15%), basketball
      (9%) and horse-riding (9%). Contact sports were the cause of injuries in 72.2%,
      with the highest incidence of trauma due to impact with another player (60%).
      Better protection of the oral and maxillofacial region is needed, especially
      during high-contact sport.

PMID- 10959367
TI  - [Cervical ectopic pregnancy].
AB  - Cervical pregnancy is a rare but serious complication. The most frequent
      presenting symptom is vaginal bleeding, and is thus common in inevitable
      abortion. Examination reveals a dilated cervix containing products of conception
      derived from the emptied uterine cavity. The pathologic criteria are cervical
      glands opposite the placental site, attachment to and actual invasion of the
      cervix by the placenta, a portion of the placenta below the posterior reflection,
      and no fetal parts in the corpus uteri. Treatment ranges from hysterectomy to
      treatment with chemical agents, mostly methotrexate. We present a case of
      ectopic, cervical pregnancy with exaggerated placental site in the cervix.

PMID- 10959368
TI  - [Caffeine intake and osteoporosis].

PMID- 10959369
TI  - [Time is running out--are we Y2K compliant (for the year 2000)?].

PMID- 10959370
TI  - [Memory circuits--holographic aspects].

PMID- 10959371
TI  - [Cell and tissue banking towards the new millennium].

PMID- 10959372
TI  - [Mass screening for osteoporosis].

PMID- 10959373
TI  - [Retinal thickness analyzer--the machine and its application].

PMID- 10959374
TI  - [Role of CT in small bowel obstruction].

PMID- 10959375
TI  - [Anesthesia for gas casualties].

PMID- 10959376
TI  - [Limb-threatening ischemia--arterial reconstruction in primary amputation?].

PMID- 10959377
TI  - [Diagnostic value of throat cultures in tonsillitis].

PMID- 10959378
TI  - [Smoking--what more can we do that we have not yet done?].

PMID- 10959379
TI  - [At another frequency].

PMID- 10959380
TI  - [Max Kassowitz (1842-1913)].

PMID- 10959381
TI  - [Evaluation of laparoscopy and laparoscopic ultrasound in diagnosis and treatment
      of pancreatic lesions].
AB  - Pancreatic lesions present a diagnostic challenge. Even modern imaging techniques
      are not sensitive enough in determining resectability of pancreatic tumors. A
      substantial proportion of patients therefore undergo unnecessary surgical
      exploration. We determined the impact of laparoscopy and laparoscopic ultrasound
      (LAPUS) examinations on surgical decision-making in 60 patients with pancreatic
      lesions. Of 48 with solid pancreatic lesions, 22 were defined by LAPUS as having
      nonresectable tumors, while conventional imaging studies defined only 9 of them
      as such. 3 of these 9 underwent successful resections of the pancreatic mass.
      Surgical intervention was ruled out by LAPUS in 16 patients (33.3%) but 26 had
      resectable lesions of whom 25 underwent surgery. 3 of this group were found to
      have nonresectable tumors at surgery, a false-positive rate of 6.2%. Overall
      sensitivity of LAPUS in our series was 88%. In 12 patients with cystic pancreatic
      lesions LAPUS contributed significantly to the preoperative decision due to clear
      imaging of the cystic lesion. Additional information was obtained from ultrasound
      guided-biopsy of the cyst wall, as well as determination of tumor-marker levels
      in the cystic fluid aspirate. LAPUS contributed significantly to operative
      management in 58%.

PMID- 10959382
TI  - [Israeli experiences of treatment of hypertension with losartan (Ocsaar)--summary
      of the treatment of 421 patients in community health centers].
AB  - The efficacy, safety and side-effects of treatment with losartan (Ocsaar) was
      studied for the first time in Israel in a large group of patients with mild to
      moderate hypertension in several community clinics. The 421 patients (51% men)
      aged 30-86 years (mean 58.6) received 50 mg of losartan daily, increased when
      necessary to 100 mg, and/or a second antihypertensive drug was given. After 4
      weeks blood pressure was normalized in 344 and after 12 weeks in 363. Side
      effects were minimal and treatment was effective in all age groups.

PMID- 10959383
TI  - [Referrals to an emergency department--are there differences between self
      referrals and referrals from general practitioners?].
AB  - The Israeli health system has been undergoing major changes in recent years.
      Considerations of cost containment have led sick funds to open new out-of-hours
      services in the community to reduce visits to hospital emergency departments.
      Referred and self-referred visits to our emergency department during a 1-month
      period were studied. Patients after trauma or whose visits resulted in
      hospitalization were excluded. Of the 505 encounters 56.3% were of women; the
      average age was 52.5 +/- 19.3 years (range 18-96). 57.4% visits were during
      working hours of primary care clinics ("working hours"), while the others were
      "out-of-hours" visits. Only 52.7% had a referral letter, 75% of them from the
      family physician. The quality of the handwriting in 46% was good, in 44% fair and
      the remaining 10% were illegible. A specific clinical question was asked in only
      16% of the letters. A third of "working-hours" visits were self-referrals, rising
      to 64% in "out-of-hours" visits (p < 0.001). The most common diagnoses in
      discharge letters were: chest or abdominal pain, asthma, back pain, headache,
      nephrolithiasis and upper respiratory tract infection. The rate of self-referrals
      was relatively high throughout the day. Cost-containment efforts did not seem to
      eliminate self-referrals with "primary care" problems. The quality of referral
      letters should be improved both with regard to format and content.

PMID- 10959384
TI  - [Nutrition for women's health].
AB  - Biological, environmental and social factors predispose women to cardiovascular
      diseases, malignancy, osteoporosis, diabetes, obesity and eating disorders. Their
      prevention requires that health services recognize women as a risk group and
      provide appropriate financial and professional resources. To develop and apply
      intervention programs for women, funding must be allocated for data collection,
      development and assessment of intervention programs and involving women in
      decision processes. We address the diseases and conditions in which nutrition may
      contribute to primary or secondary prevention of the specified diseases.

PMID- 10959385
TI  - [Hemophagocytic syndrome].
AB  - Hemophagocytic syndrome is a rare, fulminant disease characterized by generalized
      histiocytic proliferation associated with phagocytosis of erythrocytes,
      platelets, and to a lesser extent, of white blood cells. We report a 2-year-old
      boy admitted with high fever and irritability, with a rash, marked hepatomegaly
      and generalized lymphadenopathy. Liver function tests were abnormal and there was
      thrombocytopenia and hyperlipidemia. Bone marrow aspiration revealed
      hemophagocytosis. Despite intensive treatment with steroids, intravenous
      immunoglobulin and cytotoxic drugs, he died within 10 weeks.

PMID- 10959386
TI  - [Atypical mycobacterial cervical lymphadenitis in children].
AB  - Scrofula (mycobacterial cervical lymphadenitis) has been well-known for thousands
      of years. Atypical mycobacteria were first categorized by Timpe and Runyon in
      1954. Treatment has varied over the centuries, from exclusion therapy in ancient
      Greece, through digitalis, iodide, chemotherapy, and surgical excision. The
      varied differential diagnosis and consequent diagnostic and therapeutic
      challenges make reassessment of this almost forgotten disease necessary. 21
      patients with typical mycobacterial cervical lymphadenitis seen in over the past
      5 years were reviewed. Age distribution ranged from 1-14 years, with peak
      incidence at 4 years; 9 were boys and 12 girls. Most presented with nontender,
      palpable neck masses and minimal constitutional complaints. Adenopathy was
      unilateral in all cases but 2. Mycobacterium avium-intracellulare and M.
      fortuitum were the main causative organisms. All underwent excision of the
      affected nodes. Long-term follow-up has been uneventful, except for 1 case of
      local recurrence requiring re-excision. This study emphasizes the marked
      variability in the clinical presentation of scrofula in children, stressing the
      importance of the differential diagnosis between tuberculous and atypical
      mycobacterial cervical lymphadenitis. The treatment of choice for the latter is
      complete excision of the affected nodes. Other treatment is followed by
      recurrence and unnecessary complications and should be avoided.

PMID- 10959387
TI  - [Spinal and extra-spinal tumors mimicking discal herniation].
AB  - Low back pain radiating to a limb is usually caused by lumbar disc herniation.
      Tumors of the spinal cord or near the sciatic or femoral plexus can cause neural
      compression and clinical signs similar to those of disc herniation. Such tumors
      are usually misdiagnosed as discal herniation and appropriate treatment is
      delayed. We present 4 men who had tumors causing low back pain radiating to the
      leg: a 70-year-old with metastatic squamous cell carcinoma of the lung, a 20-year
      old with aneurysmal bone cyst of the vertebral column, a 52-year-old with
      retroperitoneal sarcoma and a 32-year-old who also had retroperitoneal sarcoma.
      Diagnosis and treatment were delayed because the clinical symptoms were ascribed
      to lumbar disc herniation. The latter 2 patients had CT-scans showing lumbar disc
      herniation, but similar findings are common among asymptomatic individuals. The
      differential diagnosis of low back pain radiating to the leg should include tumor
      when there is a history of cancer, pain not relieved by conservative treatment
      nor by lying down, pain is increased at night, pain accompanied by weight loss,
      and when physical examination demonstrates injury to more than 1 nerve root. In
      these circumstances work-up should include EMG, radioisotope scan and CT of the
      pelvis.

PMID- 10959388
TI  - [Malaria in travelers returning to Israel from endemic areas: diagnosis of two
      patients in a family practice].
AB  - 2 cases of malaria in family practice are described in a 26- and a 50-year-old
      woman. Both probably could have been prevented had common chemoprophylactic drugs
      been taken. The risk of malaria is greater than the risk of possible side-effects
      of the drugs commonly used by travelers for prevention. Family physicians must be
      aware of the possibility of malaria in young people with fever, especially those
      who have travelled to equatorial areas and special attention should be given to
      encourage chemoprophylaxis.

PMID- 10959389
TI  - [Nobel prize winner in medicine and physiology in 1999].

PMID- 10959390
TI  - [Probiotics--myth or benefit?].

PMID- 10959391
TI  - [Skin-sparing mastectomy--the controversy and an update].

PMID- 10959392
TI  - [Tacrolimus treatment during pregnancy in organ-transplanted women].

PMID- 10959393
TI  - [Penetrating cardiac trauma--diagnostic approach].

PMID- 10959394
TI  - [Influence of estrogen replacement therapy on cognitive function and dementia in
      postmenopausal women].

PMID- 10959395
TI  - [What do women think of pelvic examination and what are our lessons?].

PMID- 10959396
TI  - [VX--a somewhat different kid of nerve agent?].

PMID- 10959398
TI  - [Uremic pruritus: clinical characteristics, pathophysiology and treatment].

PMID- 10959397
TI  - [The serotonergic genetic component in suicidal behavior].

PMID- 10959399
TI  - [Congenital vertical talus].

PMID- 10959400
TI  - [Return to work after inguinal hernia repair--what is the optimal time and are
      there reasons for restricting a fast return to work?].

PMID- 10959401
TI  - [The other side of the coin].

PMID- 10959402
TI  - [Blunt trauma to the thoracic aorta].

PMID- 10959403
TI  - [Leopold Langstein (1876-1933)].

PMID- 10959404
TI  - Fibroblast growth factor signalling and cyclin D1 function are necessary for
      normal mammary gland development during pregnancy. A transgenic mouse approach.
AB  - A number of growth factors, growth factor receptors and cell cycle regulatory
      proteins have been implicated in the genesis of mammary carcinomas both in animal
      models as well as in human breast tumour samples. Studies on the development of
      the mammary gland has revealed that several of the proto-oncogenes, or their
      closely related gene-family members, have a function in the normal growth and
      differentiation of the gland. In this review the role of fibroblast growth factor
      signalling and the critical requirement for the cell cycle regulator, cyclin D1
      is discussed with respect to their normal function in mammary gland development
      and abnormal role in mammary carcinogenesis.

PMID- 10959405
TI  - Hepatocyte growth factor and neuregulin in mammary gland cell morphogenesis.
AB  - Organ culture and transplantation experiments in the early 1960s and 1970s have
      demonstrated that growth and morphogenesis of the epithelium of the mammary gland
      are controlled by mesenchymal-epithelial interactions. The identification of
      molecules that provide the essential signals exchanged in mesenchymal-epithelial
      interactions is an area of active research. Recent evidence suggests that
      morphogenic programs of epithelia can be triggered by mesenchymal factors that
      signal via tyrosine kinase receptors. This review concentrates on the effects of
      two mesenchymal factors, Hepatocyte Growth Factor/Scatter Factor and neuregulin,
      on morphogenesis and differentiation of mammary epithelial cells in vitro and
      signalling pathways involved during morphogenesis of mammary epithelial cells.

PMID- 10959406
TI  - Expression and localization of growth factors during mammary gland development.
AB  - Growth and differentiation of the mammary gland during development and lactation
      are controlled by complex hormonal mechanisms. Additionally growth factors are
      supposed to act as local mediators of the hormonally controlled developmental
      processes. Mammary tissue for this study was obtained from non pregnant control
      heifers, primigravid heifers (second part of pregnancy), around parturition,
      during lactation (early and late) and from dry cows. Using RT-PCR and
      ribonuclease protections assay (RPA) the expression of the following growth
      factors was studied in the different phases bovine mammary gland development:
      Insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II),
      fibroblast growth factor 1 (FGF-I), fibroblast growth factor 2 (FGF-2),
      transforming growth factor alpha (TGF-alpha). Additionally the expression of
      fibroblast growth factor receptor (FGFR) and growth hormone receptor (GHR) was
      investigated. The cellular distribution pattern of several of these growth
      factors and GHR was obtained using Immunocytochemical techniques. The detailed
      expression and localization pattern of these growth factors are presented and
      their role in the local regulation of the bovine mammary gland is briefly
      discussed.

PMID- 10959407
TI  - Involvement of growth factors in the regulation of pubertal mammary growth in
      cattle.
AB  - Pubertal mammary growth in heifers is dependent on interactions of many hormones
      and growth factors of which some are stimulatory while others are inhibitory.
      Although estrogen and growth hormone (GH) are of primary importance, more recent
      studies have suggested a role for both systemic and mammary tissue-specific
      growth factors. Growth factors may act as mediators of estrogen and GH or through
      specific effects of their own. These growth factors include insulin (INS), IGFs
      (IGF-I and IGF-II), epidermal growth factor (EGF), FGFs (FGF-1 and FGF-2), TGFs
      (TGF-alpha and TGF-beta's, amphiregulin (AR), platelets derived growth factor
      (PDGF), and mammary derived growth factor-1 (MDGF-1). Using mammary epithelial
      cells derived from prepubertal heifers and cultured in three-dimensional collagen
      gels as an in vitro model, we have investigated the mitogenic effects of a number
      of different growth factors (IGF-I, des(1-3) IGF-I, IGF-II, INS, EGF, TGF-alpha,
      AR, FGF-1, FGF-2, and TGF-beta 1). As expected, IGF-I, des(1-3)IGF-I, IGF-II and
      INS all stimulated proliferation of mammary cells with des(1-3)IGF-I being the
      most potent and INS the least potent. The mitogenic effect of IGF-I could be
      inhibited by both IGFBP-2 and IGFBP-3 showing that these binding proteins
      modulate the bioactivity of IGF-I in the mammary gland at the cellular level.
      Regulation of IGF availability by IGFBPs in the extracellular environment
      therefore is critical for IGF action in the mammary gland. Proliferation of
      mammary epithelial cells was also stimulated by growth factors of the EGF family,
      i.e. EGF, TGF-alpha and AR, however, not as much as growth factors from the IGF
      family. Members of the fibroblast growth factor family showed various mitogenic
      activities. FGF-1 stimulated DNA synthesis while FGF-2 in concentrations above 10
      ng/ml inhibited DNA synthesis. TGF-beta 1 at very low concentrations stimulated
      proliferation slightly whereas higher concentrations strongly inhibited
      proliferation of mammary epithelial cells and inhibited mitogenesis induced by
      growth factors of both the EGF- and IGF family. This shows that TGF-beta 1 is a
      very potent regulator of pubertal mammary growth.

PMID- 10959408
TI  - Insulin-like growth factor binding protein-5 (IGFBP-5) potentially regulates
      programmed cell death and plasminogen activation in the mammary gland.
AB  - This study aims to investigate the mechanism by which prolactin and GH interact
      to maintain mammary epithelial cell function in the rat. IGF-I is an important
      survival factor for the mammary gland and we have demonstrated that the effects
      of GH and prolactin involve IGF-I. GH acts by increasing IGF-I whilst prolactin
      acts by inhibiting the expression of IGFBP-5 from the mammary epithelium. During
      mammary involution, when serum prolactin levels decline, IGFBP-5 expression is
      dramatically upregulated and it binds with high affinity to IGF-I preventing IGF
      I interaction with the IGF-receptor and thus leading to epithelial cell
      apoptosis. We have identified a specific interaction of IGFBP-5 with alpha s2
      casein. This milk protein has also been shown to bind plasminogen and its
      activator tissue-type plasminogen activator (tPA) leading to enhanced conversion
      of plasminogen to plasmin. Plasmin is an important initiator of re-modelling of
      the extracellular matrix during mammary involution. A potential interaction
      between the cell death and extracellular matrix remodelling is evident from the
      observation that IGFBP-5 binds to plasminogen activator inhibitor-I (PAI-1). We
      thus hypothesized that IGFBP-5 could activate cell death by sequestration of IGF
      I and activate plasminogen cleavage by sequestering PAI-1. In support of this
      hypothesis we have shown that both prolactin and GH inhibit tPA activity and
      plasminogen activation in the involuting mammary gland. Our results suggest that
      GH and prolactin inhibit cell death and ECM remodelling via the IGF-axis and also
      indicate a novel role for the milk protein alpha s2-casein in this process. We
      have now established lines of transgenic mice expressing IGFBP-5 on the beta
      lactoglobulin promoter to explore its function in greater detail.

PMID- 10959409
TI  - Somatostatin and opioid receptors in mammary tissue. Role in cancer cell growth.
AB  - Somatostatin and opioid systems, are the two main inhibitory systems in mammals.
      Both classes of substances have been identified in normal and malignant mammary
      gland, as well as their cognitive receptors. They have been implied in the
      inhibition of cell growth of cancer cells and cell lines, in a dose-dependent and
      reversible manner. Somatostatin acts through homologous receptors (SSTRs),
      belonging to five distinct classes (SSTR1-5). We, and others have identified
      SSTR2 and 3 as been the only SSTRs present in the breast. Furthermore, opioids
      act through the three classes of opioid receptors (mu, delta,kappa). In the
      breast, kappa opioid receptor subtypes (kappa 1-kappa 3) are the most widely
      expressed. We further have shown that opioids, in addition to their binding to
      opioid receptors, compete for binding to SSTRs. This functional interaction,
      together with other identified modes of opioid action in the breast (modulation
      of steroid receptors, proteases' secretion, interaction with cytoskeletal
      elements), will be discussed, taking into consideration also the possible local
      production of casomorphins (casein-derived opioids), which are very potent
      antiproliferative agents.

PMID- 10959410
TI  - Heparan sulphate. Regulation of growth factors in the mammary gland.
AB  - Heparan sulphate (HS) is a linear glycosaminoglycan found ubiquitously on the
      surface and in the pericellular matrix of metazoan cells that is covalently
      attached to core proteins to form HS proteoglycans. HS interacts specifically
      with a large number (> 100) of extracellular regulatory proteins, many of which
      are key players in mammary development and function. HS thus acts a receptor, in
      which capacity it regulates the bioavailability, localisation and activity of
      these regulatory proteins.

PMID- 10959411
TI  - Progestin-induced mammary growth hormone (GH) production.
AB  - Toxicity studies using beagle dogs revealed in the 1980s that synthetic
      progestins may induce a syndrome of growth hormone (GH) excess, known as
      acromegaly, and the development of predominantly benign mammary hyperplasia. In
      the early 1990s is was discovered that progestin-induced GH excess in the dog
      originates within the mammary gland. This mammary-derived GH may have endocrine,
      para/autocrine as well as exocrine effects. The expression of GH mRNA is also
      found in cats and humans indicating that mammary GH expression is not unique for
      the dog. The mammary gene is identical to the pituitary-expressed gene and uses
      the same promoter. Nevertheless a striking difference exists in the mammary
      gland. Pit-1, which is a prerequisite factor for pituitary GH mRNA expression, is
      likely not involved in the mammary gene expression. These studies shed new light
      on the mechanism of progesterone-induced mammary hyperplasia and urges for
      further research on potential adverse effects of synthetic progestins.

PMID- 10959412
TI  - Translocation and action of polypeptide hormones within the nucleus. Relevance to
      lactogenic transduction.
AB  - The action of polypeptide hormones at the cell surface as mediated by
      transmembrane receptors is well recognised. However, a growing body of evidence
      also indicates that such hormones are also translocated and act directly within
      the cell nucleus. This chapter will overview what is known of the action of one
      such example, namely prolactin (PRL), from its classic action at the cell
      surface, to its novel function within the nucleus.

PMID- 10959413
TI  - Mammary gland development and the prolactin receptor.
AB  - Prolactin (PRL), synthesized by the anterior pituitary and to a lesser extent by
      numerous extrapituitary tissues, affects more physiological processes than all
      other pituitary hormones combined. This hormone is involved in > 300 separate
      effects in various vertebrate species where its role has been well documented.
      The initial step in its action is the binding to a specific membrane receptor
      which belongs to the superfamily of class 1 cytokine receptors. The function of
      this receptor is mediated, at least in part, by two families of signaling
      molecules: Janus kinases and signal transducers and activators of transcription.
      PRL-binding sites have been identified in a number of cells and tissues of adult
      animals. Disruption of the gene for the PRL receptor has provided a new animal
      model with which to better understand the actions of PRL on mammary morphogenesis
      and mammary gland gene expression. The recent availability of genetic mouse
      models provides new insights into mammary developmental biology and how the
      action of a hormone at specific stages of development can have effects later in
      life on processes such as mammary development and breast cancer initiation and
      progression.

PMID- 10959414
TI  - Paracrine mechanisms of mouse mammary ductal growth.
AB  - Ductal growth during puberty is stimulated by estrogens, which elicit their
      effects via specific estrogen receptors, ER alpha and ER beta. Analysis of mice
      with targeted disruption of ER alpha or ER beta has emphasized the importance of
      ER alpha in mammary gland development. In the mouse mammary gland, ER alpha are
      expressed in both epithelial and stromal cells (Kurita and Cunha, unpublished),
      which raises the possibility that the growth and morphogenetic effects of
      estrogen could be mediated via either epithelial or stromal ER. The aim of this
      paper is to review the role of epithelial versus stromal ER in mammary ductal
      alveolar growth to assess the importance of paracrine mechanisms.

PMID- 10959415
TI  - Targeting of PKA in mammary epithelial cells. Mechanisms and functional
      consequences.
AB  - Targeting of protein kinases, promoting association with specific partner
      molecules and localisation to particular sites within the cell, has come to be
      recognised as a key mechanism for attributing specificity to these enzymes. In
      mammary epithelial cells, the repertoire of acute regulatory roles played by
      cyclic AMP-dependent protein kinase (PKA) differs from that in other lipogenic
      cell-types. Furthermore, PKA is implicated in the regulation of mammary-specific
      function, mediating a tonic stimulation of the flux of newly-synthesised casein
      through its basal secretory pathway. Both these observations imply mammary
      specific properties of either PKA targeting systems or of PKA itself. Evidence
      for the latter is currently lacking. Pulse-chase labelling experiments in the
      presence and absence of selective effectors of PKA have enabled the site(s) of
      action of this protein kinase on casein secretion to be localised to the early
      stages of the secretory pathway. Possible mechanisms are considered for the
      physical targeting of PKA to the membrane-enclosed components of the secretory
      pathway and evidence for their occurrence in mammary epithelial cells is
      presented.

PMID- 10959416
TI  - The PEA3 group of ETS-related transcription factors. Role in breast cancer
      metastasis.
AB  - The ets genes encode eukaryotic transcription factors that are involved in
      tumorigenesis and developmental processes. The signature of the Ets family is the
      ETS-domain, which binds to sites containing a central 5'-GGAA/T-3' motif. They
      can be sub-classified primarily because of the high amino acid conservation in
      their ETS-domains and, in addition, in the conservation of other domains
      generally characterized as transactivating. This is the case for the PEA3 group,
      which is currently made up of three members, PEA3/E1AF, ER81/ETV1 and ERM, which
      are more than 95% identical in the ETS-domain and more than 85% in the
      transactivation acidic domain. The members of the PEA3 group are activated
      through both the Ras-dependent and other kinase pathways, a function which
      emphasizes their involvement in several oncogenic mechanisms. The expression
      pattern of the three PEA3 group genes during mouse embryogenesis suggests that
      they are differentially regulated, probably to serve important functions such as
      tissue interaction. Although the target genes of these transcription factors are
      multiple, their most frequently studied role concerns their involvement in the
      metastatic process. In fact, PEA3 group members are over-expressed in metastatic
      human breast cancer cells and mouse mammary tumors, a feature which suggests a
      function of these transcription factors in mammary oncogenesis. Moreover, when
      they are ectopically over-expressed in non-metastatic breast cancer cells, these
      latter become metastatic with the activation of transcription of matrix
      metalloproteinases or adhesion molecules, such as ICAM-1.

PMID- 10959417
TI  - Transcription factor NF 1 expression in involuting mammary gland.
AB  - Transcripts of each of the four NF1 genes (NF1 A, B, C (CTF/NF1) and X) are
      expressed in both lactating and involuting mouse mammary gland but there is an
      indication that increased expression of an NF1 C (CTF/NF1) transcript accompanies
      early involution. The involution-associated 74 kD NF1 and the 114 kD lactation
      associated NF1 are recognised by an anti-NF1 C-specific antibody that does not
      cross-react with other NF1 proteins. It is most likely that this
      lactation/involution switch in NF1 factors represents a change in expression of
      NF1 C (CTF/NF1) proteins.

PMID- 10959418
TI  - The Elf group of Ets-related transcription factors. ELF3 and ELF5.

PMID- 10959419
TI  - The role of Stat3 in apoptosis and mammary gland involution. Conditional deletion
      of Stat3.
AB  - STATs (signal transducer and activator of transcription) are a family of latent
      transcription factors which are activated in response to a variety of cytokines
      and growth factors. This family of signalling molecules have been implicated in
      growth, differentiation, survival and apoptosis. In this article, we will review
      work which highlights the role of individual STAT factors in mammary gland and
      demonstrate the value of genetically modified mice in defining the function of
      STAT3. Involution of the mouse mammary gland is characterised by extensive
      apoptosis of the epithelial cells and the activation of STAT3. STATs 3 and 5 have
      reciprocal patterns of activation throughout a mammary developmental cycle
      suggesting that STAT5 may be a survival factor and STAT3 a death factor for
      differentiated mammary epithelium. To clarify the role of STAT3 in mammary
      epithelial apoptosis, we have generated a conditional knockout using the lox/Cre
      recombination system. Mammary glands from crosses of transgenic mice expressing
      Cre recombinase under the control of the beta-lactoglobulin milk protein gene
      promoter with mice harbouring one floxed STAT3 allele and one null STAT3 allele,
      showed a decrease in epithelial apoptosis and a dramatic delay of the involution
      process upon forced weaning. This was accompanied by precocious activation of
      STAT1 and increases in p53 and p21 levels--these may act as a compensatory
      mechanism for initiating the eventual involution which occurs in STAT3 null
      mammary glands. This demonstrates for the first time the importance of STAT
      factors in signalling the initiation of physiological apoptosis in vivo and
      highlights the utility of the lox/Cre system for addressing the function of
      genes, which have an embryonic lethal phenotype, specifically in mammary gland.

PMID- 10959420
TI  - Synergistic and antagonistic interactions of transcription factors in the
      regulation of milk protein gene expression. Mechanisms of cross-talk between
      signalling pathways.
AB  - The stage and tissue specific expression of milk protein genes in the mammary
      gland is controlled by modular response regions with multiple binding sites for
      distinct classes of transcription factors, which either co-operate or are
      antagonistic. In addition, the activity of some of these factors is individually
      control-led by diverse extracellular signals. A well studied paradigm for a
      synergistic co-operation is the activation of beta-casein gene transcription by
      prolactin and glucocorticoids mediated by the signal transducer and activator of
      transcription STAT5 and the glucocorticoid receptor (GR). As an example for an
      antagonistic interaction we can demonstrate inhibition of prolactin signalling by
      TNF-alpha, which is mediated by NF-kappa B. In both cases, the interactions occur
      at several levels: For GR and STAT5, the synergy is discussed to be promoted by
      protein-protein interactions. Furthermore, we can demonstrate a co-operation
      between GR and STAT5 in DNA binding by a mechanism, which is dependent on the
      integrity of the DNA binding domain of the GR and on the existence of half
      palindromic GR binding sites in the hormone response region. Indirect effects of
      glucocorticoids by modulation of the expression of secondary genes are also
      important. They might account for the observed enhancement of prolactin induced
      tyrosine phosphorylation of STAT5 by glucocorticoids. For NF-kappa B and STAT5,
      one component of the antagonism is the inhibition of STAT5 tyrosine
      phosphorylation by activation of NF-kappa B. Another potential mechanism is the
      inhibition of DNA binding of STAT5 due to overlapping binding sites for STAT5 and
      NF-kappa B in the beta-casein gene promoter. Thus, synergistic and antagonistic
      interactions between GR, NF-kappa B, and STAT5 involve (a) cross-talk mechanisms
      influencing the activation of STAT5 and (b) promoter-dependent interactions
      modulating the DNA binding activity of the transcription factors.

PMID- 10959421
TI  - Nucleosome organisation of the beta-lactoglobulin gene. Transcription complex
      formation.
AB  - In most mammals, the major whey protein beta-lactoglobulin (beta lg) represents a
      marker for tissue-specific, temporally regulated gene expression in the mammary
      gland. Prolactin, the major lactogenic stimulus which activates beta lg
      expression acts through a cytoplasmic signalling cascade ending in the activation
      of the transcription factor STAT5. Although much is known about the complexities
      of this signalling cascade, little is known about how this transcription factor
      functions within the context of chromatin. Using DNaseI as a probe of chromatin
      structure we have identified temporally regulated elements within the ovine beta
      lg gene domain. The appearance of these hypersensitive sites accompanies changes
      in expression state of the beta lg gene. Changes in DNaseI hypersensitivity at
      the proximal promoter region, while reflecting STAT5 activation, is not dependent
      upon STAT5 interaction at this site. We have mapped the nucleosome positions over
      the entire beta lg gene, both in vitro using the monomer extension assay and in
      vivo using cuprous phenanthroline to probe for nucleosome-linker positions. The
      specific positioning pattern detected, which reflects strong sequence-directed
      positioning over the proximal promoter, complement the STAT5 consensus sites
      within this region. The comparison of both the functional and chromatin data
      enables a model for beta lg gene transcription to be developed.

PMID- 10959422
TI  - Chromatin remodeling in hormone-dependent and -independent breast cancer cell
      lines.
AB  - Chromatin restricts the accessibility of DNA to regulatory factors; its
      remodelling over the regulatory regions contributes to the control of gene
      expression. An increasing number of evidence links defects in chromatin
      remodelling machinery and cancer. Our aim is to elucidate the role of chromatin
      structure in the control of the expression of hormone-induced genes in breast
      cell lines oestrogen-dependent or -independent for growth. Mammary tumour growth
      is controlled by steroid hormones via their nuclear receptor and by growth
      factors via tyrosine kinase receptors. 50% of these tumours elude to hormonal
      control. This limits the anti-oestrogen therapy. As a model, we have analysed in
      several cell lines the chromatin organisation of the regulatory regions of two
      genes, pS2 that is associated with a good prognostic, and cathepsin D (catD) that
      is a bad prognostic marker. The expression of the two genes is oestrogen
      regulated in oestrogen-dependent cell line MCF7. In contrast in the hormone
      independent cell line MDA MB 231, pS2 is not expressed and catD is constitutively
      expressed. Within the regulatory regions of pS2 gene, we have localised two
      regions that undergo a hormone-dependent change in chromatin structure in MCF7
      cells but not in MDA MB 231 and that can be correlated with gene expression. In
      contrast catD regulatory regions did not display hormone-dependent changes in
      chromatin structure, suggesting that hormone regulation takes place within
      regions with a constitutively open chromatin structure.

PMID- 10959423
TI  - The use of transplanted mammary gland to study cancer signalling pathways.
AB  - Mammary epithelium can be genetically manipulated by reconstituting a mammary
      gland, in an animal, from epithelium and a mammary fat pad from which the
      endogenous epithelium has been removed at 3 weeks of age. Genes can be introduced
      into the epithelium before transplantation using retrovirus vectors. To remove
      genes from the epithelium at present requires epithelium to be transplanted from
      knockout donor mice, but this is a valuable extension of knockout technology, as
      (a) it creates knockout epithelium in a normal stromal and systemic environment,
      or vice versa, and (b) where the knockout mouse does not survive into adulthood,
      epithelium can be rescued from embryos after about 12 days of gestation, and
      grown to form mature mammary epithelium in a normal recipient mammary fat pad.

PMID- 10959424
TI  - Development of mammary gland requires normal beta 1-integrin function.
AB  - To study the role of beta 1-integrins in mammary gland development we have
      generated transgenic mice expressing a dominant negative mutant of the beta 1
      integrin chain in the mammary epithelium. The transgenic glands presented a
      delayed development in pregnancy and lactation due to decreased epithelial cell
      proliferation and increased apoptosis, whereas at the beginning of lactation,
      expression of milk proteins, WAP and beta-casein was diminished. In correlation
      with transgene expression, the basement membrane component, laminin, and the beta
      4 integrin were accumulated at the lateral surface of luminal epithelial cells,
      revealing defects in polarization. Our data show that beta 1-integrins are
      involved in vivo in the control of proliferation, apoptosis, differentiation, and
      maintenance of baso-apical polarity of mammary epithelium.

PMID- 10959425
TI  - Repression of the putative tumor suppressor gene Bard1 or expression of
      Notch4(int-3) oncogene subvert the morphogenetic properties of mammary epithelial
      cells.
AB  - We have investigated whether repression of the putative tumor suppressor gene
      BARD1 or expression of the Notch4(int-3) oncogene in non-tumorigenic mammary
      epithelial cells affects their in vitro morphogenetic properties. Bard1 (Brca1
      associated ring domain) is a protein interacting with Brca1 and thought to be
      involved in Brca1-mediated tumor suppression. To investigate the potential role
      of Bard1 in mammary gland development, we repressed its expression in TAC-2
      cells, a murine mammary epithelial cell line which, when grown in three
      dimensional collagen gels, forms branching ducts in response to hepatocyte growth
      factor (HGF) and alveolar-like cysts in response to hydrocortisone. Whereas Bard1
      repression did not markedly modify the tubulogenic response of TAC-2 cells to
      HGF, it dramatically altered cyst development, resulting in the formation of
      compact cell aggregates devoid of central lumen. In addition, when grown to post
      confluence in two-dimensional cultures, Bard1-suppressed TAC-2 cells overcame
      contact-inhibition of cell proliferation and formed multiple cell layers. The
      Notch4(int-3) oncogene, which codes for a constitutively activated form of the
      Notch4 receptor, has been reported to induce undifferentiated carcinomas when
      expressed in the mammary gland. The potential effect of activated Notch4 on
      mammary gland morphogenesis was investigated by retroviral expression of the
      oncogene in TAC-2 cells. Notch4(int-3) expression was found to significantly
      reduce HGF-induced tubulogenesis and to markedly inhibit hydrocortisone-induced
      cyst formation. In addition, Notch4(int-3) expressing TAC-2 cells formed
      multilayers in post-confluent cultures and exhibited an invasive behavior when
      grown on the surface of collagen gels. Taken together, these results indicate
      that both repression of Bard1 and expression of Notch4(int-3) disrupt cyst
      morphogenesis and induce an invasive phenotype in TAC-2 mammary epithelial cells.

PMID- 10959426
TI  - Oncogene mediated signal transduction in transgenic mouse models of human breast
      cancer.

PMID- 10959427
TI  - Caspases: decoders of apoptotic signals during mammary involution. Caspase
      activation during involution.
AB  - At weaning most of the alveolar epithelial cells in the mammary gland die by
      apoptosis and are removed by phagocytosis. Caspases are a family of aspartate
      specific cysteine proteases. Activation of caspases is generally thought to
      represent a major and irreversible event in the apoptotic process. We analyzed
      caspase expression and activation during mammary gland involution. A quantitative
      RT-PCR based approach revealed that levels of mRNA expression of several caspases
      are induced during involution. Using an antibody that specifically recognizes
      activated caspases we measured a transient induction of caspase activity in situ
      and found a maximal activation at days two and three of involution. These data
      were corroborated by monitoring caspase-3 like activity in mammary extracts with
      a synthetic DEVD-afc peptide as caspase-3 substrate. Using Fas-deficient mice we
      present evidence that the Fas signaling pathway is not essential for caspase
      activation and apoptosis during mammary gland involution. In summary, signaling
      pathways during involution seem to involve activation of caspases as
      intraepithelial triggers of mammary epithelial cell apoptosis.

PMID- 10959428
TI  - The role of plasminogen activator in the bovine mammary gland.

PMID- 10959429
TI  - Regulation and nutritional manipulation of milk fat. Low-fat milk syndrome.

PMID- 10959431
TI  - Genetic polymorphisms in milk protein genes and their impact on milk composition.
AB  - About 40 different genetic variants are present at bovine milk protein loci and
      considerable differences in allele frequencies were observed among breeds.
      Advanced electrophoretic methods and recently, the DNA technology have been
      applied for identification and characterisation of milk protein genetic variants.
      Mutations with impact on gene expression have been identified. The influence of
      lactoprotein genetic variants on milk composition and cheese making ability has
      been studied extensively. The most prominent effects have been found for beta-LG
      A/B and kappa-CN A/B in cattle and alpha s1-CN E in goat.

PMID- 10959430
TI  - Effect of feeding pattern and behaviour on hormonal changes and milk composition.
AB  - There is no doubt that feeding and nutrient availability modify the metabolism
      through hormonal changes. It is otherwise interesting to better define the
      influence of the imposed or freely chosen meal distribution during the day; in
      fact the daily feed intake in a relatively short time, namely during the
      daylight, seems to induce a clear anabolic phase in afternoon-night (high insulin
      and low urea) and a catabolic one in the morning (low insulin and high urea);
      among the possible consequences, the lower fat content in the morning milking and
      the higher one in the afternoon, are of great importance. The factors that can
      influence these daily changes are many, namely the meal size, the day or night,
      the stage of lactation and perhaps a genetic effect. These results can be useful
      for a better interpretation of blood parameters and of the relationships between
      feeding and milk composition.

PMID- 10959432
TI  - Mammary gland immunology around parturition. Influence of stress, nutrition and
      genetics.
AB  - Adequate immune functions are essential for the defence against udder infections.
      Detailed knowledge about the immune response and important defence factors is
      essential in order to find new ways for the prevention and treatment of udder
      infections leading to mastitis. Work should be concentrated on ways of minimising
      the negative influence on immune functions and/or ways of stimulating these
      functions, especially during periods of immune suppression. A depression of
      important immune functions has been reported around parturition and there is a
      higher prevalence of clinical mastitis and other diseases during this period.
      Immunosuppression is often associated with high levels of glucocorticoids in
      blood, a common finding around parturition and during stressful conditions. A
      number of stressors are present around calving, e.g. parturition, onset of
      lactation and changes in feeding and management regimes. Adequate management
      including feeding strategies and routines are important for the immune functions.
      Metabolic stress as well as deficiencies in vitamins and minerals around
      parturition and during the first month of lactation can have a negative influence
      on the immune functions and thereby increase the risks for udder infections and
      mastitis. There seem to be a genetic variability in certain immune functions
      among periparturient cows. This might indicate a possibility to find markers for
      genetic selection of individuals with a well-developed immune system without
      negative effects on milk productivity.

PMID- 10959433
TI  - Cells and cytokines in inflammatory secretions of bovine mammary gland.
AB  - In response to invading bacteria, the mammary gland is protected by a variety of
      defence mechanisms, which can be separated into two distinct categories: innate
      immunity and specific immunity. Milk somatic cells consist of several cell types,
      including neutrophils, macrophages, lymphocytes and a smaller percentage of
      epithelial cells. In the healthy lactating mammary gland, macrophages are the
      predominant cell type whereas neutrophils are the major cell population during
      early inflammation. Following a bacteria invasion, neutrophil recruitment is
      elicited by inflammatory mediators that are produced in the infected gland by
      cells, possibly macrophages, activated by bacteria phagocytosis or responding to
      bacterial toxins or metabolites. Several cytokines, including interleukin- (IL-)
      1 beta, IL-6, IL-8, tumour necrosis factor- (TNF-) alpha and interferon- (IFN-)
      gamma are known to be important to elicit the acute phase response and allow the
      accumulation of leukocytes at the site of infection. In addition to their role in
      early non-specific defences, macrophages also play a key role in the specific
      immune system, as antigen processing and presenting cells for the T cells. Few
      lymphocytes are found in milk of healthy glands where the predominant phenotype
      is CD8+ T cells. During the inflammatory reaction, T cells are recruited in milk
      and CD4+ cells become the predominant phenotype. The understanding of the
      specific and nonspecific immune mechanisms involved in the mammary gland defence
      against invading bacteria may lead to the development of new vaccines and to the
      use of cytokines to design immunomodulatory strategies for the control of bovine
      mastitis.

PMID- 10959434
TI  - Immune surveillance of mammary tissue by phagocytic cells.
AB  - The leukocytes in milk consist of lymphocytes, neutrophil polymorphonuclear
      leukocytes (PMN) and macrophages. Lymphocytes together with antigen-presenting
      cells function in the generation of an effective immune response. Lymphocytes can
      be divided into two distinct subsets, T- and B-lymphocytes, that differ in
      function and protein products. The professional phagocytic cells of the bovine
      mammary gland are PMN and macrophages. In the normal mammary gland macrophages
      are the predominate cells which act as sentinels to invading mastitis causing
      pathogens. Once the invaders are detected, macrophages release chemical
      messengers called chemoattractants that cause the directed migration of PMN into
      the infection. Migration of neutrophils into mammary tissue provides the first
      immunological line of defense against bacteria that penetrate the physical
      barrier of the teat canal. However, their presence is like a double-edged sword.
      While the PMN are phagocytosing and destroying the invading pathogens, they
      inadvertently release chemicals which induces swelling of secretory epithelium
      cytoplasm, sloughing of secretory cells, and decreased secretory activity.
      Permanent scarring will result in a loss of milk production. Resident and newly
      migrated macrophages help reduce the damage to the epithelium by phagocytosing
      PMN that undergo programmed cell death through a process called apoptosis.
      Specific ligands on the neutrophil surface are required for directed migration
      and phagocytosis. In response to infection, freshly migrated leukocytes express
      greater numbers of cell surface receptors for immunoglobulins and complement and
      are more phagocytic than their counterparts in blood. However, phagocytic
      activity rapidly decreases with continued exposure to inhibitory factors such as
      milk fat globules and casein in mammary secretions. Compensatory hypertrophy in
      non-mastitic quarters partially compensates for lost milk production in diseased
      quarters. Advances in molecular biology are making available the tools,
      techniques, and products to study and modulate host-parasite interactions. For
      example the cloning and expression of proteins that bind endotoxin may provide
      ways of reducing damaging effects of endotoxin during acute coliform mastitis.
      The successful formation of bifunctional monoclonal antibodies for the targeted
      lysis of mastitis causing bacteria represents a new line of therapeutics for the
      control of mastitis in dairy cows.

PMID- 10959435
TI  - Mammary gland immunology and neonate protection in pigs. Homing of lymphocytes
      into the MG.
AB  - Since placenta of pregnant sows are impermeable to immunoglobulin passage, the
      neonates are born agammaglobulinemic; although immunocompetent, they are unable
      to develop rapidly an immune response which will protect their systemic and
      mucosal compartments; thus their survival depend upon the passive acquisition of
      maternal immunity including at least 3 components: i) a systemic humoral
      immunity, transmitted through colostrum conveying mainly by IgG; these IgG are
      transferred from maternal serum via Fc gamma receptors on the epithelial cells of
      mammary gland (MG). ii) a local humoral immunity, especially secretory IgA
      (IgAs), transmitted mainly by milk (lactogenic immunity) until weaning. IgAs are
      secreted by MG recruited plasma cells and are excreted in milk via secretory
      component of epithelial cells: these IgA exhibit a specificity for the antigens
      present in the maternal digestive tract, the so-called "entero-mammary link";
      this link is due to the migration of lymphocytes from the gut to the mammary
      gland; they are recruited from the blood via the interaction of their homing
      receptor (alpha 4 beta 7) with the developmentally regulated mucosal vascular
      addresin MadCAM-1. In the MG, MadCAM-1 increased in pregnancy (probably under
      oestrogenic stimulation) but regressed in lactation; its density is closely
      related to the T cell numbers in MG; in contrast the increase in plasma cell
      numbers is not related to MadCAM-1 density. Thus IgA precursor cells (alpha 4
      beta 7 B cells) seem to be recruited by a milk B cell chemoattractant. On the
      other hand, presence of T and B lymphocytes in MG (some of them originating from
      the systemic compartment), sustains the attempts of MG immunization and the
      results sustain the view of a true local immune response. iii) possibly but not
      formally proved, a cellular immunity transmitted via maternal immunocompetent
      cells present in mammary secretions; the exported lymphocytes may represent a
      selected population of lymphocytes after their passage through the MG epithelium.

PMID- 10959436
TI  - Relationship between teat tissue immune defences and intramammary infections.
AB  - The teat is the main entrance for pathogens into the mammary gland. It also acts
      as a sensory, motor and primary defence organ. This latter function is important
      in preventing intramammary infections while efficiency in preventing new
      infections is determined by teat tissue integrity. Machine milking may evoke
      mechanical and circulatory impairment in teat tissues. These local metabolic
      disorders may decrease the efficiency of the local immune defence mechanisms.
      Teat tissue changes can be estimated by measuring teat thickness before and after
      milking. Experimental and field studies showed a high correlation between changes
      in thickness and infection risk. Teats with > 5% change in thickness have
      significantly increased teat duct colonisation rates and intramammary infection
      rates. The link between changes in teat thickness and infections should be found
      in changes in local immune defences and measurable changes in cytological and
      biochemical immune factors are expected. Indeed, the application of experimental
      milking conditions (i.e. no pulsation milking and positive pressure milking)
      showed to have a significant influence on some non specific immune factors in
      teat secretion. Positive pressure milking increases PMNs content and decreases
      macrophages content of teat secretion. Some enzymes such as NAGase and lysozyme
      were decreased by positive pressure milking, the concentration of the same
      enzymes were higher after no pulsation milking. A better knowledge on the
      interaction between the teat apex immune defense mechanisms and the machine
      milking process is necessary to reduce the new infection rate of the bovine
      mammary gland.

PMID- 10959437
TI  - Immunological aspects of pregnancy-associated glycoproteins.
AB  - The incidence of severe cases of acute E. coli mastitis in dairy cows is highest
      during early lactation. This phenomenon has been associated with a decreased
      function and decreased numbers of circulating polymorphonuclear neutrophil
      leukocytes (PMN). The cause of this impaired function and decreased number is
      poorly understood. Stress, hormonal and metabolic alterations around parturition
      and the onset of lactation may play a role in this phenomenon. Several molecules,
      such as cortisol and beta-hydroxybutyrate have been found to alter the oxidative
      burst activity of circulating PMN around parturition. Pregnancy-Associated
      Glycoprotein (bPAG) could also be involved. The theory of immunosuppression by
      bPAG was investigated because analogous glycoproteins produced by the placenta of
      other species exert local immunosuppression in order to maintain the
      histoincompatible feto-maternal unit. The production and subsequent release into
      the maternal circulation of bPAG is ensured by the binucleate cells from the
      trophoblast and starts already at implantation. However, peak levels are only
      reached 1 week before parturition. Due to the long half-life time of this
      molecule, high levels are found in plasma until 2 weeks after calving. The co
      occurrence of the impairment of PMN oxidative burst activity in the early
      postpartum period and a peak in plasma bPAG concentrations might support the
      hypothesis of an immunosuppressive effect of PAG. Moreover, an inhibitory effect
      of bPAG on the proliferation of bovine bone marrow progenitor cells has been
      found recently in our laboratory. bPAG occurs in colostrum, but its effect on
      milk cells has not been clarified. It is concluded that interaction between the
      physiology of reproduction and lactation on the one side and immune function on
      the other side in dairy cattle requires further research.

PMID- 10959438
TI  - Vaccines against bovine mastitis due to Streptococcus uberis current status and
      future prospects.
AB  - The prevalence of bovine mastitis in the UK has been reduced over the past twenty
      five years due to the implementation of a five-point control plan aimed at
      reducing exposure, duration and transmission of intramammary infections by
      bacteria. This has markedly reduced the incidence of bovine mastitis caused by
      bacteria which show a contagious route of transmission but has had little effect
      on the incidence of mastitis due to bacteria which infect the gland from an
      environmental reservoir. Streptococcus uberis is one such bacterium which is
      responsible for a significant proportion of clinical mastitis worldwide. The
      inadequacies of the current methods of mastitis control have led to the search
      for additional measures to prevent intramammary infection by this bacterium. A
      live vaccine in combination with an intramammary administration of a soluble cell
      surface extract was shown to induce protection of the mammary gland from
      experimental challenge with S. uberis. Protection was strain specific, but was
      achieved in the absence of opsonic activity and without a large influx of
      neutrophils. One hypothesis is that protection was achieved by reducing the rate
      of bacterial growth in vivo. This view has led to the identification and
      exploitation of a novel plasminogen activator as a vaccine antigen. Vaccines
      containing this antigen conferred cross strain protection.

PMID- 10959439
TI  - Inborn errors of cholesterol biosynthesis.
AB  - Disorders of cholesterol biosynthesis have recently emerged as important errors
      of metabolism that collectively have taught us many new genetic and biochemical
      lessons. Whereas most metabolic diseases are characterized by exclusively or
      largely postnatal biochemical toxicities or deficiencies, disorders of
      cholesterol biosynthesis are notable for their severe effects on prenatal
      development. The remarkable embryonic consequences of abnormal cholesterol
      biosynthesis are exemplified by Smith-Lemli-Opitz syndrome (SLOS), a well-known
      multiple congenital anomaly syndrome only recently discovered to be caused by a
      deficiency in the last step in cholesterol biosynthesis. Equally surprising has
      been the discovery that primary defects of cholesterol biosynthesis cause several
      different forms of congenital skeletal dysplasia, most notably X-linked dominant
      chondrodysplasia punctata, or Conradi-Hunermann syndrome. Yet another sterol
      disorder, desmosterolosis, caused by defective activity of desmosterol reductase,
      combines a severe osteosclerotic skeletal dysplasia with multiple embryonic
      malformations similar to those of SLOS. The discovery of the biochemical basis of
      these diverse genetic disorders has provided not only accurate biochemical
      methods for their diagnosis and prenatal diagnosis, but also new insights into
      the biochemistry of vertebrate embryonic development. Among the lessons we have
      learned from the study of inborn errors of cholesterol biosynthesis, one of the
      most important is that the abnormal cholesterol metabolism of SLOS impairs the
      function of "Sonic hedgehog" and other related embryonic "signaling proteins"
      that help determine the vertebrate body plan during the earliest weeks of
      embryonic development. Most significant clinically has been the realization that
      many of the postnatal clinical problems of patients with SLOS are direct
      consequences of the inability to synthesize the large amounts of cholesterol
      needed for growth and for the synthesis of compounds derived from cholesterol,
      such as steroid hormones. In addition to the important finding that supplementary
      cholesterol eliminates or ameliorates many of the feeding and growth problems of
      SLOS, the discovery that the autistic behaviors of children with SLOS can be
      reduced or even eliminated by treatment with supplementary dietary cholesterol
      has been one of the most startling. Moreover, clinical and basic research on
      prenatal cholesterol nutrition in SLOS and various animal model systems has
      delineated a previously unrecognized system for the delivery of low-density
      lipoprotein cholesterol from the mother to the developing embryo. The many
      discoveries engendered by these experiments of nature argue that there are
      heretofore unrecognized beneficial effects of cholesterol, especially in
      children, and that we should consider very carefully possible adverse effects
      that the popular war against cholesterol may have on the prenatal and postnatal
      development of children.

PMID- 10959440
TI  - Atherogenesis in children: implications for the prevention of atherosclerosis.
AB  - Although it is frequently stated that "atherosclerosis begins in childhood," it
      is not so frequently stated that only the first stage of atherosclerosis--the
      innocuous, highly reversible fatty streak--occurs in childhood. The more harmful
      second stage of atherosclerosis, the atheromatous plaque, does not appear until
      after puberty in boys and much later in girls. The purpose of this review is to
      emphasize the natural history of atherosclerosis, particularly as it pertains to
      children, and to consider its implications for the prevention of atherosclerosis.
      Present evidence supports the view that intervening in childhood (2-15 years)
      with low-fat, low-cholesterol diets or even worse, lipid-lowering drugs, to
      prevent plaque formation in adulthood is wasted effort. Furthermore, the data
      show that children respond more poorly to lipid-lowering diets than do adults,
      and that the emphasis on low-fat diets for children leads some parents to overdo
      the guidelines and unwittingly push their children into malnutrition. The program
      adopted by Health Canada on the advice of pediatricians in that country to taper
      fat intake from 40% of energy at 2 years of age to 30% of energy at the
      conclusion of linear growth (late adolescence) is a step forward.

PMID- 10959441
TI  - Improving the health of patients with cystic fibrosis through newborn screening.
      Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

PMID- 10959442
TI  - Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.
AB  - Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our
      increasing knowledge since its classic description by Gee in 1882. Its hallmark
      feature of recurrent, explosive bouts of vomiting punctuating periods of normal
      health causes substantial medical morbidity (50% of patients require intravenous
      therapy), as well as significant time lost from school (20 school absences per
      year) and work. Limited epidemiologic data indicate that CVS may occur more
      commonly than previously thought, affecting as many as 1.9% of school-aged
      children. Besides the relentless vomiting, the child usually has pallor (87%),
      lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is
      evidence of clinical and physiologic overlap among CVS, abdominal migraine, and
      migraine headaches. We propose revised criteria for abdominal migraine that
      include pain as the predominant and consistent symptom, lack of abnormal
      screening tests, and in retrospect, either subsequent development of migraines or
      positive response to antimigraine medication. Besides migraines, other etiologic
      possibilities include mitochondrial DNA mutations, ion channelopathies, excessive
      hypothalamic-pituitary-adrenal axis activation, and heightened autonomic
      reactivity. The differential diagnosis includes idiopathic CVS (88%);
      gastrointestinal disorders (7%), including serious surgical disorders (e.g.,
      malrotation); and extraintestinal disorders (5%), including serious surgical
      (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation
      disorder). Within the idiopathic group, there may be migraine, Sato's
      neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance
      of triggers, prophylactic medication, supportive care, abortive medication, and
      family support. In the future, investigation into mitochondrial DNA mutations,
      ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin
      receptor physiology and pharmacology may help discover the etiology and
      pathogenesis of this disorder.

PMID- 10959443
TI  - Childhood migraine.
AB  - Migraines are a common and often undiagnosed and undertreated problem in children
      of all ages. Migraine symptoms can vary dramatically in terms of character and
      severity, from brief self-limited headaches to prolonged events with complex
      neurologic and systemic symptoms. Identification of migraines requires an index
      of suspicion in any child with acute recurrent headaches or neurologic symptoms.
      Diagnosis remains predominately based on the patient's history of symptoms and
      supported by a positive family history. Neurodiagnostic tests are often
      unnecessary and of value predominately to exclude nonmigraine disorders that may
      present with similar symptoms. A number of recent advances in our understanding
      of the pathophysiology and genetics of migraines have occurred, and continued
      progress in these exciting areas of investigation is anticipated. Identification
      of genetic markers in individuals with FHM is potentially the first step in
      discovery of genetic markers that may be useful in other migraine syndromes and
      may lead to the development of new therapeutic interventions. The movement from a
      vascular to integrated neurovascular pathogenesis for migraine headaches is
      already being translated into the study of new pharmacologic treatments, such as
      nitric oxide inhibitors and continued development of 5-HT1 agonist (triptans)
      medications. Although not currently approved for use in children, triptans are
      being widely evaluated in clinical trials. As additional triptans and new dosage
      formulations are developed and approved, it is anticipated that the treatment of
      migraine headaches in children may change significantly in the next several
      years.

PMID- 10959444
TI  - Leave no "stone" unturned: understanding the genetic bases of calcium-containing
      urinary stones in children.
AB  - Urinary stones in children are being recognized with increasing frequency.
      Formerly thought to be the result of dehydration, urinary obstruction, or
      infection, most urinary calculi in children now are recognized to have an
      underlying metabolic abnormality. A number of challenges face pediatricians in
      evaluating and treating children with urinary stone disease. Often the clinical
      symptomatology is nonspecific and lacks the excruciating renal colic seen in
      adults. Furthermore, diagnostic clinical laboratory values vary with age and must
      be differentiated from normal values reported for adult patients. Both
      environmental and genetic factors are responsible for urinary stones. Many stones
      have a hereditary basis. Exciting new information is developing about the genetic
      propensity for urinary stones. Current medical therapies attempt either to reduce
      the production of a lithogenic solute or to increase urinary solubility. New
      therapies for prevention and treatment of urinary stone disease are likely to
      evolve as our understanding of the pathogenesis of these conditions grows.

PMID- 10959445
TI  - Bartter and Gitelman syndromes.
AB  - Since the initial description in the 1960s of patients with seemingly inherited
      disorders characterized by hypokalemia and metabolic alkalosis, the
      pathophysiologic processes underlying Bartter and Gitelman syndromes have
      generated tremendous study and speculation. Recently described mutations in genes
      encoding transport proteins important in sodium and chloride reabsorption in the
      thick ascending limb of Henle and distal convoluted tubule have confirmed these
      processes as the proximate defects in Bartter and Gitelman syndromes,
      respectively. Basic understanding of the role of these proteins in normal sodium
      and chloride homeostasis, and review of the secondary mediators stimulated by
      loss of their function provide insight into the clinical manifestations and
      response to treatment observed in these disorders.

PMID- 10959446
TI  - Major changes in sickle cell disease.
AB  - Clinical, molecular, and genetic advances have revealed new pathophysiologic
      insights and treatments for the growing number of recognized hematologic and
      nonhematologic abnormalities in sickle cell disease. Treatment targets of
      cellular dehydration, sickle hemoglobin concentrations, endothelial dysfunction,
      and abnormal coagulation regulation have been validated as potential therapy. New
      uses for transfusion therapy hold the promise of decreased major symptoms of
      acute chest syndrome, stroke, and severe pain crises, but at the expense of
      increased risk for transfusion reactions, infections, and iron overload.
      Accumulated experience with autologous, chimeric, and stem cell bone marrow
      transplantation holds promise for a small percentage of patients with disease.
      Patient selection, suitable donors, and early mortality are still limiting
      factors. Genetic manipulation, which offers hope for ameliorating the disease in
      a larger percentage of patients, is progressing slowly. Combination and staged
      therapies will be developed and matched to the severity and progression of the
      patient's disease. Strategies for prevention of major organ damage to the brain,
      heart, lungs, and kidneys will be prospectively evaluated and refined.

PMID- 10959447
TI  - Asthma: the new advances.
AB  - There has been significant interest in halting and even reversing the trend of
      increasing asthma mortality and morbidity. One strategy is to recognize
      persistent asthma within the first few years of onset and to intervene early with
      anti-inflammatory therapy. This review summarizes the new information available
      on asthma pathogenesis that has helped to shape a change in direction of viewing
      asthma as an episodic disease to one that is chronic in nature. At the root of
      this change is the recognition that asthma is a chronic inflammatory disease of
      the airways. Inhaled steroids are recognized as the most potent anti-inflammatory
      medication available, and they are now profiled as the cornerstone in the
      management of chronic persistent asthma. This dramatic change in direction has
      significant implications for the primary care physician, especially the
      pediatrician, who is most likely to see asthma in its early stages. Recent
      interest has been directed toward defining a "window of opportunity" for
      intervention that could significantly affect the course of the disease. Although
      this may be an exciting opportunity to control the development of asthma, one has
      to be cognizant of potential risk of early and long-term therapeutic
      intervention. This review provides a perspective on our present knowledge and the
      rationale for early intervention, as well as speculates about how this new
      information will continue to play a role in advancing asthma care and moving
      toward a "cure" of this disease.

PMID- 10959449
TI  - Antivirals other than for HIV therapy.
AB  - This review concentrates on drugs directed at viruses other than HIV and does not
      include anti-HIV drugs. Many antivirals are nucleoside analogues, although new
      classes of enzyme inhibitors are being developed for treatment of HIV (proteases)
      and enteroviruses. Antisense drugs and receptor blockers have recently been
      approved. Regardless of mechanism, antivirals are predominantly virustatic, not
      virucidal, and usually require help from the host immune system to either
      completely eliminate pathogens (e.g., influenza) or to provide sufficient immune
      surveillance to prevent a latent pathogen from reactivating (e.g., the
      herpesviruses). Viruses by nature are intracellular pathogens, using the host
      cell to produce progeny. Often the viral pathogen uses the host cell machinery or
      enzyme system to facilitate replication. At times the virus usurps nearly the
      entire intracellular system for replication and may shut down all functional host
      cell output for host-determined products. Because of the intracellular nature of
      viruses and because viruses use many "normal" host cell factors, functions, and
      systems for replication, antivirals can have notable toxicities to host cells. As
      antivirals inhibit viral activity in the viral-infected host cells (these
      encompass a minority of the total host cell numbers), they may also negatively
      affect functions in the virus-uninfected host cells. These alterations may be
      biochemical, detected only if sought specifically, or clinically obvious
      toxicities. Either may limit the use of some antivirals to severe or life
      threatening situations.

PMID- 10959448
TI  - Emergency contraception.
AB  - High rates of adolescent pregnancy remain a challenge for health care providers.
      For most sexually active adolescents, pregnancy is unintended. Emergency
      contraception, also called the "morning-after-pill" or postcoital contraception,
      is a way to prevent pregnancy after unprotected intercourse. In the United
      States, three forms of emergency contraception currently are available: high-dose
      combination estrogen and progestin pills, high-dose progestin-only pills, and
      postcoital insertion of a copper intrauterine device. The postcoital intrauterine
      device is used infrequently. When emergency contraceptive pills (ECPs) are taken
      within 72 hours of unprotected intercourse, they reduce the risk of pregnancy by
      at least 75%. However, they are most effective if taken within 24 hours of
      coitus. Eleven brands of pills currently are marketed in the United States that
      conform to the regimens approved by the Food and Drug Administration (FDA) for
      this indication. Recently, two prepackaged ECPs were approved by the FDA. The
      only medical contraindication to prescribing ECPs is pregnancy. The most common
      side effects are nausea and vomiting, followed by menstrual disturbances, breast
      tenderness, abdominal cramping, dizziness, headache, and mood changes. Because
      vomiting can compromise the efficacy of ECPs, routine pretreatment with an
      antiemetic is recommended. Primary care providers can reduce unintended
      adolescent pregnancy by routinely counseling adolescents at all office visits
      about the existence of emergency contraception and by prescribing it in advance
      and over the telephone.

PMID- 10959450
TI  - Anaerobic infections in children.
AB  - Anaerobic bacteria commonly cause infection in children. Anaerobes are the most
      predominant components of the normal human skin and mucous membrane bacterial
      flora, and are therefore a common cause of bacterial infections of endogenous
      origin. Because of their fastidious nature, they are difficult to isolate from
      infectious sites and are often overlooked. Anaerobic infections can occur in all
      body sites, including the central nervous system, oral cavity, head and neck,
      chest, abdomen, pelvis, skin, and soft tissues. Anaerobic bacteria colonize the
      newborn after delivery and have been recovered from several types of neonatal
      infections. These include cellulitis of the site of fetal monitoring, neonatal
      aspiration pneumonia, bacteremia, conjunctivitis, omphalitis, and infant
      botulism. The lack of directing adequate therapy against these organisms may lead
      to clinical failures. Their isolation requires appropriate methods of collection,
      transportation, and cultivation of specimens. Treatment of anaerobic infection is
      complicated by the slow growth of these organisms, by their polymicrobial nature,
      and by the growing resistance of anaerobic bacteria to antimicrobials.
      Antimicrobial therapy is often the only form of therapy required, whereas in
      other cases it is an important adjunct to a surgical approach. Because anaerobic
      bacteria generally are recovered mixed with aerobic organisms, the choice of
      appropriate antimicrobial agents should provide for adequate coverage of both
      types of pathogens.

PMID- 10959451
TI  - [Platelets and heart disease: how much more can basic science influence clinical
      practice?].

PMID- 10959452
TI  - [Ventricular function curves with and without pericardium: analysis of
      pericardial pressures].
AB  - Simultaneous right and left ventricular function curves (VFC, R, L) were obtained
      in a canine model, (open chest preparation), with and without pericardium.
      Preload and afterload conditions for the right and left ventricles were
      controlled. VFC were constructed from zero to 25 mmHg of ventricular end
      diastolic pressures and by increasing the cardiac output from 50 to 250 mL/kg
      1min-1. Both, right and left VFC showed an initial steep rise at low filling
      pressures and then flattened off to a plateau at high filling pressures. The best
      mathematical model that fitted with the VFC, with and without the pericardium was
      the parabola (r2 = 0.71, 0.72 respectively). After pericardiectomy R and L VFC
      were displaced to the left of the VFC with pericardium and a decrease in filling
      pressures were noted at the same points of cardiac output, findings that suggest
      a restraining effect of the pericardium. By subtracting the filling pressures
      obtained with pericardium from those without pericardium at the same levels of
      cardiac output, pericardial pressures were derived. In all the range of the VFC
      the pericardial pressures were positive, and this pressure increase as cardiac
      output increase. Thus the transmural pressure was never cero, for both right and
      left ventricles. The observed relation for the R and L filling pressures, derived
      from a polynomial equation of second order suggest a small although not
      unimportant effect of the pericardium at normal filling pressures, and a very
      substantial influence at high levels of cardiac output. The demarcation between
      small and major effects appears in the upper range of normal filling pressures in
      this dynamic approach of the pericardial pressures.

PMID- 10959453
TI  - [Myocardial perfusion evaluated with a 2-isotope technique. Experience with the
      first 1600 cases in Mexico].
AB  - SPECT has a high sensitivity for the diagnosis of coronary artery disease. Dual
      isotope protocol using rest thallium and stress MIBI was introduced in Mexico 4
      years ago. This protocol reunite the advantages of both radiotracers for the
      study of myocardial perfusion. We present our experience of the first three
      years. One thousand six hundred patients were studied with suspected myocardial
      ischemia; 288 were excluded because of an absence of a proper follow up. In 895
      of the 1312 patients a coronariography was performed. Images were evaluated by
      dividing the heart in 20 segments using a 5 points scale (0 = normal to 4 =
      absence of perfusion). It was considered a perfusion defect when a segment had a
      score greater or equal to 2 and the SPECT study was considered abnormal if two or
      more segments had a MIBI stress score equal or greater than 2. The global
      sensitivity for diagnosis of ischemia was 96.28%. Dual isotope method is
      appropriate for the diagnosis of ischemic heart disease. It has a high
      sensitivity and specificity for the recognition of global coronary disease and
      for specific coronary territories. This work constitutes the greatest series in
      Latin America that uses this diagnosis method.

PMID- 10959454
TI  - [Usefulness of transesophageal echocardiography in the diagnosis of aortic
      intramural hematoma].
AB  - Aortic intramural hematoma or atypical aortic dissection is an aortic dissection
      without intimal tear nor flow communication and it may be the first step of a
      typical dissection. We describe five cases, in which transesophageal
      echocardiography detected intramural hematoma of the aorta. Transesophageal
      echocardiography is a safe, accurate and specific method that allows bedside
      diagnosis as well as follow-up of patients with hematoma of the aorta.

PMID- 10959455
TI  - [Electrocardiography and echocardiography aspects of hypertrophic myocardiopathy
      in pediatrics].
AB  - Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease, characterized by
      asymmetric hypertrophy of the left and/or right ventricle with disarray of
      myocardial fibers. In order to know its clinical and electrocardiographic
      manifestation in the pediatric age group, we made a retrospective study of 24
      cases from 1986 to 1995. There were: 15 girls and 9 boys, with a mean age of 6
      years (age range: 1 month to 17 years). Clinical manifestations were dyspnea
      (71%), syncope (42%) and palpitations (42%). Physical examination disclosed an
      aortic systolic murmur in all patients, a mitral regurgitation in 42% and
      physical signs of congestive heart failure in 54% of patients. Chest X rays
      showed cardiac enlargement in 71% and pulmonary capillary hypertension in 42%.
      The most frequent ECG abnormalities were: a prolonged time in the intrinsecoid
      deflection onset on leads corresponding to the affected region, more or less deep
      and clean Q waves on leads aVF, aVL, V5 and V6, as well as supraventricular and
      ventricular rhythm disturbances in 11 patients (46%) with and without congestive
      heart failure. Bidimensional echocardiography confirmed antero-septal hypertrophy
      in all patients. The mortality rate was 17%. HCM is rare disease in the pediatric
      age group. Mortality increases when congestive heart failure and arrhythmias are
      present. Treatment must be individualized in all cases.

PMID- 10959456
TI  - [Maximal cardiac rate during treadmill exertion test in 1853 healthy subjects.
      Its relation with age and under the atmospheric conditions of Mexico City].
AB  - INTRODUCTION: The relation between heart rate and age during the exercise test is
      dependent on the altitude over the sea level in which the test is made.
      OBJECTIVE: To observe the behavior of the heart rate during a maximal exercise
      test and its relation to age and to the altitude of Mexico City. METHOD:
      Observational, non randomized study of 1,853 healthy subjects who underwent
      maximal exercise test done with Bruce's protocol, in the Department of Cardiology
      of the Spanish Hospital of Mexico City. RESULTS: The distribution by age groups
      showed a normal curve. They were divided by gender (67% males and 33% females)
      with a mean age of 47.6 +/- vs 49.6 +/- 13.7 years respectively (p = 0.003).
      Maximal heart rate according to gender (167.9 +/- 17.4 vs 160 +/- 18.2 bpm, p =
      0.001). Trained vs sedentary (85.7% vs 14.3%). Maximal heart rate by grade of
      training (169.1 +/- 16.4 vs 167.6 +/- 17.8 bpm, p > 0.05) and the lineal
      correlation of maximal heart rate dependent on age of the subject (r-0.61, Y =
      204.37 + (-0.810*X), p = 0.001). CONCLUSIONS: The maximal heart rate during
      maximal exercise test at the altitude of Mexico City is lower than those reported
      in the literature. This is statistically significant and depends on age and it
      does not bear any relationship to the degree of training, at least in our
      subgroup of subjects studied. The same is true for females and the dependence on
      age remains the same too.

PMID- 10959457
TI  - [Cardiopulmonary dynamics during a maximal exertion test in Mexican endurance
      athletes].
AB  - AIM: To search for cardiopulmonary (CP) kinetic and dynamic differences between
      Mexican resistance athletes (RES = 10) and non athletes (NON = 19). METHOD: From
      the expired volume (Ve), measured by an open circuit spirometry, we calculated
      both VO2 and VCO2 during stress test while the volunteer pedalled seated on an
      electronic cycloergometer that started at 50 W.2 min-1 followed by increments of
      25 W.2 min-1 each, until VO2max was reached. The exercise transient time course
      (min) response (VO2, VCO2, Ve and heart rate, HR; and also O2 pulse, PulO2) was
      transformed to seconds and modelled by computer using linear regression technique
      by the interactive minimum squares method, and the mean response time (MRT) was
      used as an overall kinetic CP parameter. RESULTS: The transient MRTs for VO2,
      VCO2 and Ve were slow in RES compared to NON. While the transient CP dynamics in
      NON lasted MRT_VO2 < (MRT_PulO2, MRT_FC) < MRT_VCO2 < MRT_Ve; the RES: both
      MRT_PulO2 and MRT_HR shifted to the right ((MRT_VO2, MRT_VCO2) < (MRT_PulO2,
      MRT_FC) < MRT_Ve). The relationships between the best sport profit mean velocity
      and both the MRT_VO2, MRT_VCO2 and MRT_PulO2 (GEK = gas exchange kinetics) showed
      fast_RES and slow_GEK, and slow_RES and fast_GEK. CONCLUSION: The transient CP
      kinetics was slow in RES compared NON. It is possible to distinguish
      cardiopulmonary kinetic differences among resistance athletes holding different
      sport profiles.

PMID- 10959458
TI  - [Percutaneous treatment of multiple heart defects].
AB  - We describe our experience in 6 cases with multiple congenital heart defects
      treated by percutaneous intervention. Their age ranged from 2.3 to 10 years (mean
      6.1), with follow-up from 1 to 84 months (mean 28.8). Two cases had coarctation
      of the aorta (AC) and persistent ductus arteriosus (PDA). Two patients had
      pulmonary valve stenosis (PVS) and PDA, one case with aortic stenosis (AE) and
      PDA and one case with AC, mitral stenosis and subaortic stenosis (Shone's
      Syndrome). Ductus arteriosus was occluded in all patients with Gianturco coils or
      Rashkind occluder. The valvular gradient post balloon decreased in cases with AC
      from 46 to 9 mmHg, with PVS from 110 to 10 mmHg and with AE from 40 to 14 mmHg.
      In a 8 year old boy with Shone's syndrome, we performed angioplasty of aortic
      coarctation, mitral valvuloplasty with Inoue catheter. He was referred to surgery
      for subaortic repair stenosis. All are asymptomatic at follow-up. In conclusion;
      percutaneous intervention is possible in patients with multiple congenital heart
      defects.

PMID- 10959459
TI  - [Dilated cardiomyopathy induced by ectopic atrial tachycardia].
AB  - The deleterious effect of chronic or incessant supraventricular tachycardia on
      ventricular function is well-known and it has been demonstrated than can
      ultimately lead to dilated cardiomyopathy if unrecognized. Any variety of
      supraventricular tachycardia with chronic evolution may lead to left ventricular
      dysfunction, ectopic atrial tachycardia because of its persistent nature, often
      incessant and poorly responsive to antiarrhythmic drugs is a frequent cause of
      reversible congestive heart failure in patients without other demonstrable
      organic heart disease. Five patients (aged 14 to 52 years) were referred with
      symptoms of heart failure, NYHA functional class II (one patient), class III (one
      patient) and class IV (3 patients) associated with an incessant ectopic atrial
      tachycardia. Four patients underwent radiofrequency catheter ablation of the
      ectopic focus and one patient was treated with amiodarone. All patients were
      successfully treated and the echocardiographic assessment of left ventricular
      function indicated regression of the cardiomyopathy picture with recovery of
      systolic function, (mean left ventricular ejection fraction 39.2 +/- 6.1% before
      vs mean 62.4 +/- 4.8% after (p < 0.01). The clinical and echocardiographic
      picture of cardiomyopathy induced by incessant ectopic atrial tachycardia is
      reversible after successful treatment. This stresses the necessity of recognizing
      such arrhythmia as cause of primary heart failure.

PMID- 10959460
TI  - [ST segment elevation, right bundle branch block and sudden death: Brugada's
      syndrome].
AB  - Brugada's syndrome is one of the main causes of sudden death in young adults
      without a structural heart disease. This is an electrical cardiac illness
      secondary to a mutation of SCN5A gene of chromosome 3 that has a dominant
      autosomic transmission pattern. This mutation implies the dysfunction of the
      sodium channel that increases the Ito, loosing the dome of the epicardiac action
      potential phase two. An "all or none" repolarization pattern ensues and gives
      rise to a phase two reentry. This kind of reentry is responsible for the
      initiation and perpetuation of malignant ventricular arrhythmias among these
      patients. The clinical characteristics of the syndrome are the right bundle
      branch block, ST segment elevation from V1 to V3 leads and sudden death or
      syncope. In some patients, a pharmacological test must be done with ajmaline or
      procainamide to unmask the electrocardiographic changes. At present, the only
      effective treatment is the implantable cardioverter defibrillator (ICD). This
      device has the capability to reduce mortality from 40% annually to 0% at ten
      years. Pharmacological treatment is not useful.

PMID- 10959461
TI  - [Low concentrations of high-density lipoproteins (HDL) in plasma and coronary
      artery disease].

PMID- 10959462
TI  - Ocular factitious disorder presenting as endophthalmitis.

PMID- 10959463
TI  - Guidelines for screening examinations for retinopathy of prematurity. Canadian
      Association of Pediatric Ophthalmologists Ad Hoc Committee on Standards of
      Screening Examination for Retinopathy of Prematurity.

PMID- 10959464
TI  - Determining the information needs for prevention of vision loss strategies in
      Canada. Public Health Task Force for Vision and Ophthalmology.

PMID- 10959465
TI  - Evaluation of the iScreen digital screening system for amblyogenic factors.
AB  - BACKGROUND: A digital photoscreener, the iScreen screening system, is now
      available to detect amblyogenic factors. We carried out a prospective study to
      evaluate the accuracy of the device in detecting anisometropia, significant
      refractive error, strabismus and opacities of the ocular media. METHODS: A total
      of 449 consecutive patients (median age 7 years) from a private pediatric
      ophthalmology practice underwent screening with the iScreen photoscreener
      operated by a minimally trained technician. The results were compared to the
      masked clinical examination of a pediatric ophthalmologist. RESULTS: The iScreen
      device had a sensitivity of 92.4%, specificity of 89.1%, positive predictive
      value of 94.1% and false-negative rate of 13.8%. Of the 21 patients with a false
      negative result, 12 had myopia of less than -1.50 dioptres. High hyperopia was
      missed in two patients, high astigmatism in one, unequal cylindrical error in one
      and strabismus in five. INTERPRETATION: The iScreen digital photoscreener
      produced accurate and timely screening for potentially amblyogenic defects in the
      study population.

PMID- 10959466
TI  - Ultrasound detection of posterior scleral bowing in young patients with choroidal
      melanoma.
AB  - BACKGROUND: In evaluating young patients with choroidal melanomas, which are
      uncommon in people less than 30 years old, we noted that some had the ultrasound
      appearance of posterior scleral bowing. The purpose of this study was to
      determine the incidence of posterior scleral bowing in young patients with
      choroidal melanoma. METHODS: We reviewed the ultrasonograms of 24 patients less
      than 30 years of age (mean age 25 years [standard deviation (SD) 4.7 years]) who
      presented to an ocular oncology service in Toronto between May 1984 and May 1997.
      In all cases the diagnosis was choroidal melanoma. Histologic specimens were
      available in six cases. RESULTS: Scleral indentation posterior to the normal
      curvature of the globe was identified in 14 patients (58%). These patients had a
      mean tumour height of 4.4 mm (SD 2.0 mm) and mean tumour diameter of 9.5 mm (SD
      2.9 mm). In the 10 patients with no scleral bowing the mean tumour height was 5.7
      mm (SD 3.1 mm) and mean tumour diameter 11.5 mm (SD 3.8 mm). Pathological study
      (results available in nine cases in the scleral bowing group and four cases in
      the group without bowing) showed that all the tumours in the former group and
      three of those in the latter group were of the more indolent cell types, either
      mixed with predominantly spindle cells, or spindle cell. The six patients with
      histologic specimens were all in the scleral bowing group. The histologic
      features supported the ultrasound finding of posterior scleral bowing. No
      transscleral invasion occurred over the tumour region. INTERPRETATION: Posterior
      bowing of the sclera at the tumour site was observed in over half of young
      patients with choroidal melanoma. This phenomenon can be detected by
      ultrasonography and has a different appearance from that of choroidal excavation.

PMID- 10959467
TI  - Converting visual acuity to utilities.
AB  - BACKGROUND: Utility theory can be used to quantify dysfunction associated with
      various diseases and thus can represent a "hard" measure of quality of life. By
      determining utility values, one can compare the quality of life of patients with
      ocular disease to that of patients with non-ophthalmic problems. We performed a
      study to determine whether utility values from patients with ocular disease are
      associated with clinical variables, including visual acuity in the better-seeing
      eye, and to develop a mathematical method for converting visual acuity to utility
      value, if there is an association between the two. METHODS: Cross-sectional
      study. A total of 239 patients from a tertiary care retinal practice with various
      ocular conditions, including macular degeneration, cataract, glaucoma and
      diabetic retinopathy, were interviewed under standardized conditions to determine
      their utility values by the time trade-off technique. Visual acuity, duration of
      visual loss and number of concomitant conditions were also determined. Multiple
      linear regression was performed to determine which variables were associated with
      utility values. RESULTS: The mean acuity in the better-seeing eye was 0.479 (near
      20/40 vision). The mean utility value was 0.72. Accordingly, the average patient
      in our series was willing to trade 2.8 of every 10 remaining years of life to
      obtain perfect vision in both eyes. Utility value was significantly associated
      with visual acuity in the better-seeing eye (F = 69.1, p < 0.001). Other
      variables were not significantly associated with utility value. The association
      with duration of visual loss approached statistical significance (p = 0.075).
      Utility values (U) for patients with ocular disease can be derived from the
      following formula: U = (0.374)(visual acuity in better-seeing eye) + 0.514.
      INTERPRETATION: Utility values from patients with ocular disease were strongly
      associated with visual acuity and could be estimated mathematically.

PMID- 10959469
TI  - Ways of knowing.

PMID- 10959468
TI  - Inadvertent intracorneal and intraocular corticosteroid injection.

PMID- 10959470
TI  - New NMHA Web site features depression screening tool.

PMID- 10959471
TI  - Measuring sexual arousal.
AB  - The impact of sexual offenses and abuse is incalculable, both on the victims
      themselves and the society responsible for protecting them. Identifying people
      who sexually offend against adults and children and preventing them from engaging
      in abusive behavior in the future requires valid and reliable methods that
      accurately identify the perpetrators' characteristics and measure treatment
      effectiveness. This article reviews the literature on penile plethysmography
      (PPG), a mechanism by which erectile response to deviant sexual stimuli can be
      measured.

PMID- 10959473
TI  - Sexual predators in nursing homes.

PMID- 10959472
TI  - The antidepressant nefazodone. A review of its pharmacology, clinical efficacy,
      adverse effects, dosage, and administration.
AB  - Nefazodone is an antidepressant medication which received approval from the Food
      and Drug Administration for treatment of major depressive disorder in 1994. This
      article summarizes the pharmacodynamics, pharmacokinetics, adverse effects, and
      drug interactions of nefazodone as well as its administration and dosing
      schedule. The potential efficacy of nefazodone in treating anxiety, premenstrual
      syndrome, chronic pain conditions, and sleep disturbances also is summarized.
      Nefazodone has a favorable side effects profile which makes it an attractive
      alternative option for patients who withdraw from treatment when they develop
      adverse effects to other available antidepressants.

PMID- 10959474
TI  - A new model for the mental health nursing change of shift report.
AB  - Nursing shift reports are intended to enhance the continuity and quality of
      nursing care delivered by providing results of nursing assessments, summarizing
      medical information, and drawing attention to specific nursing interventions and
      goals anticipated during the upcoming shift. In this article, contemporary
      literature on shift reports is reviewed with specific attention to the unique
      characteristics and problems that commonly occur in change of shift reports in a
      mental health setting. The framework proposed is Gordon's functional health
      patterns because it provides a holistic structure for organizing patient data in
      a clear, objective manner. Additional methods for enhancing shift reports are
      recommended, including the use of specific behavioral descriptions, the inclusion
      of data from targeted nursing assessments, and the discussion of alternative care
      approaches that support the development of consistent, collaborative nursing
      interventions across shifts. A case example is used for demonstration.

PMID- 10959475
TI  - Improved efficiency of gene transfer to the transplanted lung by retrograde
      vascular gene delivery.
AB  - Experiments were designed to evaluate the efficiency of antegrade compared to
      retrograde vascular gene transfection of donor lungs used for transplantation.
      Rat donor lungs (n = 5/group) were transduced with an adenoviral vector encoding
      for beta-galactosidase (AdbetaGal), either antegrade in the pulmonary artery
      (Group A, 3 x 10(8) pfu, Group B, 3 x 10(9) pfu) or retrograde into the pulmonary
      vein (Group C, 3 x 10(8) pfu), immediately after pneumoplegia. After storage at 4
      degrees C for 1 h, the transduced lungs were transplanted orthotopically in
      syngeneic animals. The lungs were assessed for transgene expression by ELISA and
      X-Gal-staining at day 7 after operation. Inflammation was graded based on the
      extent of inflammatory cell infiltration. Transgene expression was similar
      between Groups A (1.7 +/- 0.7 ng/mg protein) and B (2.1 +/- 1.0 ng/mg protein).
      With retrograde delivery, there was a four-fold (8.3 +/- 2.6 ng/ mg protein)
      increase (P < 0.05) in transgene expression compared to either group A or B. In
      all groups, pneumocytes were transduced most frequently. The degree of
      inflammation correlated positively with the extent of transgene expression (r =
      0.75, P < 0.01). The efficiency of vascular gene delivery to transplanted lungs
      can be improved by retrograde delivery of the vector via the pulmonary vein.
      Transgene expression predominates in pneumocytes following both antegrade and
      retrograde delivery. The severity of inflammation in the transplanted lung
      appears to correlate with the extent of transgene expression.

PMID- 10959476
TI  - Sequential analysis of adhesion molecules and their ligands in rat renal
      allografts during the development of chronic rejection.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) are important in endothelial cell-leukocyte interactions. In this
      sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and
      VLA-4 as well as major histocompatibility complex class II antigens (MHC class
      II), and interleukin-2-receptor (IL-2R) were investigated during the development
      of chronic renal allograft rejection in a rat model. The time-related expression
      of adhesion molecules and their ligands in the graft was correlated to the
      chronic allograft damage index (CADI). In association with an initial short
      immune activation, there was a significant ICAM-1 and VCAM-1 induction in the
      vascular endothelium and the tubular epithelium. In the interstitium, there was
      infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-1, as well
      as activation markers MHC class II and IL-2R. Thereafter, the expression declined
      together with the increase of CADI-values. In end-stage chronic rejection, there
      was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there
      were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and
      their ligands are involved in the induction phase of the process but no longer in
      the later stages of chronic rejection.

PMID- 10959477
TI  - Differences in binding of glucocorticoid receptor to DNA in chronic renal graft
      rejection.
AB  - Although chronic rejection is the most common reason for late allograft loss, its
      pathophysiology and etiology are unclear. Attempts to prevent chronic rejection
      are now focused on the modulation of transcriptional regulation. We evaluated the
      ability of glucocorticoid receptors (GR) to bind to the DNA binding site in
      peripheral blood mononuclear cells (PBMC) of five patients with chronic rejection
      and seven without it. Using an electrophoretic mobility shift assay, we measured
      the amount of nuclear glucocorticoid receptor capable of binding to its specific
      DNA recognition sequences, termed glucocorticoid response elements (GRE). GR
      binding was significantly greater in control patients than in those with chronic
      rejection (P < 0.01). The retarded band was almost undetectable in two patients
      with chronic rejection even though they were taking more prednisolone than the
      seven control patients, all of whom had clearly identifiable retarded bands.
      These results suggest a decreased ability of GR to bind to GRE in chronic
      rejection, resulting in a reduced ability to block key proinflammatory promoter
      sites. This reduced binding may be one molecular basis of chronic rejection.

PMID- 10959478
TI  - Increased urinary nitrate excretion associated with hepatic allograft rejection
      in experimental rat models and clinical cases.
AB  - In this study, we investigated the relationship between excretion of urinary
      nitrate as a stable end-product of nitric oxide (NO) metabolism and hepatic
      allograft rejection. In experimental rat models, hepatic allograft rejection was
      associated with increased nitrate excretion with a peak on postoperative day 5.
      The severity of the hepatic allograft rejection was dependent on the increased
      urinary nitrate excretion. No significant increase in urinary nitrate excretion
      was observed in cases in which effective immunosuppression was achieved.
      Inducible nitric oxide synthase mRNA expression was upregulated parallel to
      interferon-gamma gene expression in the graft-infiltrating mononuclear cells and
      spleen cells from the recipients. In clinical cases, urinary nitrate excretion
      increased parallel to increased serum cytosolic enzymes that accompanied
      rejection. These results suggest that urinary nitrate excretion is a useful
      indicator for the surveillance of graft rejection and the monitoring of
      therapeutic effects of antirejection treatments.

PMID- 10959479
TI  - Comparative report on transplantation and relevant ethical problems in five
      European countries, and some reflections on Japan.
AB  - Comparison of transplantation medicine in Sweden, Denmark, Germany, Spain and
      Portugal reveals many and important differences with respect to frequency of
      transplantations, frequency of life donations, legal regulations and influence of
      the family on organ donation. The differences observed are at least partly
      related to cultural and value differences between the various countries, but many
      questions need to be studied systematically and in more detail before useful
      conclusions can be drawn. One study would have to address the problem of how
      differences in the family influence on organ donation can be explained. Another
      question needing further clarification concerns the exact meaning of "medical
      decision" and "medical criteria" because these terms, on which access to- and
      selection from the waiting list largely depends, are equivocally defined and seem
      to differ according to different traditions. Open questions also arise with
      respect to the influence of "closeness or distance" on medical decision making.
      The findings indicate that it would be premature to propose common guidelines to
      be observed within Europe as long as the above mentioned and some further
      questions have not been systematically studied and thoroughly analyzed.

PMID- 10959480
TI  - Constitutive and acquired resistance to calcineurin inhibitors in renal
      transplantation: role of P-glycoprotein-170.
AB  - The present study examines whether resistance to Cyclosporin A (CyA) and
      Tacrolimus (FK506) develops in T cells from individual patients and the role of P
      glycoprotein 170 (P-gp) in mediating drug resistance. IC50s were established for
      CyA and FK506 in cell cultures from 46 renal allograft recipients. P-gp
      expression and functional activity were determined by flow cytometry. Mean ID50
      for CyA was 29 microg/li (range 2.5-100) and for FK506 1.2 microg/li (range 0.085
      5.5). The sensitivities to the two drugs were correlated (P = 0.0001). There was
      variation in the ratio of the ID50s depending on the drug used for treatment (P =
      0.02). There was no difference in P-gp expression and functional activity in
      patients with sensitive or resistant cells. The data indicate an association
      between the sensitivities to CyA and FK506 and evidence of selective resistance
      to whichever drug was used. P-gp drug transport does not explain this variation.

PMID- 10959481
TI  - Cystatin C--an accurate marker of glomerular filtration rate after renal
      transplantation?
AB  - The performance of serum cystatin C as a screening marker of reduced creatinine
      clearance in renal transplantation was evaluated and compared to serum
      creatinine. In addition we studied whether cystatin C accurately reflects
      creatinine clearance over the entire range of transplant function. Serum cystatin
      C, serum creatinine, and creatinine clearance were measured in 110 adult renal
      transplant recipients. Cystatin C detected reduced creatinine clearance with the
      high sensitivity of 95%. Serum cystatin C and serum creatinine did not differ
      regarding 90 and 95% sensitivity, derived from the receiver-operating
      characteristics plot. We demonstrated a strong correlation and linear association
      between 1/cystatin C and creatinine clearance over the entire range of transplant
      function, equivalent to that of 1/creatinine. In summary, serum cystatin C
      accurately reflects creatinine clearance over the entire range of transplant
      function and is as efficacious as serum creatinine to detect reduced creatinine
      clearance in renal transplant recipients.

PMID- 10959482
TI  - Lamivudine as first- and second-line treatment of hepatitis B infection after
      liver transplantation.
AB  - Lamivudine and famciclovir have expanded therapeutical options for HBV infection
      after liver transplantation. First studies confirm good antiviral effects of
      both, but at present the major problem seems to be a rapid resistance formation
      in immunosuppressed patients. Thirty-four adult patients with HBV recurrence
      despite passive immunoprophylaxis and seven with de novo infection after
      orthotopic liver transplantation (OLT) were treated with 100-150 mg lamivudine
      daily. Patients were either treated directly after infection (n = 14) or after
      breakthrough of viral replication during an initial famciclovir therapy (n = 27).
      All patients except two responded to treatment with a reduction of serum HBV-DNA
      of over 50%. Thirty-one patients (76%) turned HBV-DNA-negative during lamivudine
      therapy. Viral breakthrough was observed in 14 of these patients after 4-13
      months of treatment. A total of 17 patients (40%) remained HBV-DNA-negative for
      more than 12 months. Only nine patients eliminated HBsAg, of which four had and
      an HDV coinfection. None of the HBeAg-positive patients converted to anti-HBe.
      Most patients showed a prompt and significant reduction of aspartate
      aminotransferase (ALAT) levels. No severe complications occurred. Therefore, a
      safe and effective therapy of HBV infection after transplantation is possible
      with lamivudine. Viral replication is suppressed even in patients who revealed
      breakthrough during famciclovir therapy. Resistance formation as a major drawback
      occurred in one third of the patients within the first year of treatment.

PMID- 10959483
TI  - During ischemia-reperfusion in rat kidneys, heat shock response is not regulated
      by expressional changes of heat shock factor 1.
AB  - Ischemia-reperfusion injury is known to induce the inducible form of the 70 kDa
      heat shock protein HSP70i (or HSP72) mainly via rapid activation of heat shock
      transcription factor 1 (HSF1). However, little is known about the regulation of
      the HSF1 gene. We therefore studied the time course of HSF1 mRNA transcription
      and its relation to the expression pattern of the HSP70i mRNA in the renal
      cortex, this being the most vulnerable and functionally most important part of
      the kidney, after different periods of unilateral renal ischemia (10-180 min) and
      reperfusion (up to 60 min) in male Wistar rats (10 weeks old). Immediately after
      ischemia there was a significant induction of HSP70i genes. While HSP70i
      expression constantly increased (up to 4-fold) during reperfusion, even to a
      higher extent with prolongation of ischemia, HSF1 mRNA remained constitutively
      expressed under all conditions. Thus, we conclude that during ischemia
      reperfusion in rat kidneys, the heat shock response is regulated by other means
      than expressional changes of HSF1.

PMID- 10959484
TI  - Normothermic recirculation reduces primary graft dysfunction of kidneys obtained
      from non-heart-beating donors.
AB  - Our aim was to analyze the short- and long-term function of kidneys procured from
      non- heartbeating donors (NHBD) by means of three techniques: in situ perfusion
      (ISP), total body cooling (TBC) and normothermic recirculation (NR). Fifty-seven
      potential NHBD were included. Mean warm ischemia time was 68.9 +/- 35.6 min.
      Forty-four kidneys were obtained from donors perfused with ISP, 8 with TBC, and 8
      with NR. Eighteen kidneys (32%) started functioning immediately, 29 (52%) showed
      delayed graft function (DGF) and 9 (16%) showed primary non function (PNF). The
      actuarial graft survival rate was 76.4% at 1 year and 56% at 5 years. The patient
      survival rate was 89.3% at 5 years. Incidence of DGF and PNF was significantly
      lower in kidneys perfused with NR than those with ISP or TBC (P < 0.01). Duration
      of DGF was shorter in kidneys obtained through TBC than in kidneys obtained with
      ISP (P < 0.05). In conclusion, NR reduces the incidence of DGF and may be
      considered the method of choice for kidney procurement from NHBD.

PMID- 10959485
TI  - Inhibition of microglial nitric oxide production by hydrocortisone and
      glucocorticoid precursors.
AB  - Viral and bacterial infection in the central nervous system can induce nitric
      oxide production, which serves as a major host defense against invading
      microorganisms. Glucocorticoids secretion is enhanced and immune responses are
      diminished in stressed animals or in patients suffering depression. Using N9
      microglial cells, this study tested the hypothesis that glucocorticoids and their
      precursors caused an impaired immune defense in animals because these compounds
      could inhibit microglial nitric oxide production. Results indicated that both
      hydrocortisone and the synthetic glucocorticoid, dexamethasone, were potent
      inhibitors of the microglial nitric oxide production. While glucocorticoid
      precursors were not as potent as hydrocortisone, the potency of these precursors
      increased linearly as they advanced on the biosynthesis pathway. Northern and
      Western blot analyses indicated that hydrocortisone and dexamethasone might
      interfere with the inducible nitric oxide synthase at either the transcription or
      at the post-translational level, depending on the concentrations used. These
      results suggest that glucocorticoids have the ability to block nitric oxide
      production by microgila, which could partially explain the impaired immune
      protection against infection in the central nervous system in stressed animals.

PMID- 10959486
TI  - Potentiation of carbachol-induced Ca2+ release by peroxynitrite in human
      neuroblastoma SH-SY5Y cells.
AB  - We have investigated the effect of 3-morpholinosydnonimine (SIN-1), a
      peroxynitrite donor, on carbachol-induced increase in intracellular Ca2+
      concentration ([Ca2+]i) in human neuroblastoma SH-SY5Y cells by means of single
      cell imaging of [Ca2+]i. SIN-1 potentiated carbachol-induced [Ca2+]i rise
      regardless of external Ca2+, and the potentiation was completely inhibited by
      superoxide dismutase, indicating that peroxynitrite may enhance Ca2+ release from
      intracellular stores. On the other hand, SIN-1 reduced carbachol-induced inositol
      1,4,5-trisphosphate (IP3) formation. Genistein, a tyrosine kinase inhibitor,
      potentiated carbachol-induced rise of [Ca2+]i regardless of external Ca2+. These
      results suggest that peroxynitrite may potentiate the release of Ca2+ from
      intracellular stores through the perturbation of regulation in tyrosine
      phosphorylation-dephosphorylation system.

PMID- 10959488
TI  - The expression of Cdk5, p35, p39, and Cdk5 kinase activity in developing, adult,
      and aged rat brains.
AB  - The expression of cyclin-dependent kinase 5 (Cdk5) and its regulatory subunits,
      p35 and p39, was investigated in rat brain from embryonic day 12 (E12) to
      postnatal 18 months (18M). The Cdk5 protein levels increased from E12 to
      postnatal day 7 (P7) and remained at this level until 18M. The Cdk5 kinase
      activity and the levels of both p35 mRNA and protein were low at E12, became
      prominent at E18-P14 but then decreased in the adult and aged rat brains of 3M to
      18M. In comparison, the expression pattern of p39 appeared to have an inverse
      relationship to that of Cdk5 and p35. In regional distribution studies, p35
      protein levels and Cdk5 kinase activity were significantly higher in the cerebral
      cortex and hippocampus, but lower in the cerebellum and striatum. These results
      suggested that Cdk5, p35 and p39 might have region-specific and developmental
      stage-specific functions in rat brain.

PMID- 10959487
TI  - Effect of chronic variate stress on thiobarbituric-acid reactive species and on
      total radical-trapping potential in distinct regions of rat brain.
AB  - It has been suggested that oxidative stress is involved in aging and
      neuropathologic disorders. In addition, chronic stress and high corticosterone
      levels are suggested to induce neuronal death. The aim of this study is to verify
      the effect of chronic variate stress on lipoperoxidation and on the total radical
      trapping potential (TRAP) in hippocampus, hypothalamus and cerebral cortex. Adult
      male Wistar rats were submitted to different stressors during 40 days. Lipid
      peroxide levels were assessed by the thiobarbituric acid reactive species (TBARS)
      reaction, and TRAP was measured by the decrease in luminescence using the 2-2'
      azo-bis(2-amidinopropane)-luminol system. The results showed that in cerebral
      cortex homogenates chronic stress induces an increase in oxidative stress. In
      hypothalamus a decreased lipoperoxidation was observed, however TRAP showed no
      difference. In hippocampus no difference was observed. We concluded that
      prolonged stress induces oxidative stress which varies selectively with the brain
      region.

PMID- 10959489
TI  - Endogenous GM1 ganglioside of the plasma membrane promotes neuritogenesis by two
      mechanisms.
AB  - The influence of GM1 on the neuritogenic phase of neuronal differentiation has
      been highlighted in recent reports showing upregulation of this ganglioside in
      the plasma and nuclear membranes concomitant with axonogenesis. These changes are
      accompanied by alterations in Ca2+ flux which constitute an essential component
      of the signaling mechanism for axon outgrowth. This study examines 2 distinct
      mechanisms of induced neurite outgrowth involving plasma membrane GM1, as
      expressed in 3 neuroblastoma cell lines. Growth of Neuro-2a and NG108-15 cells in
      the presence of neuraminidase (N'ase), an enzyme that increases the cell surface
      content of GM1, caused prolific outgrowth of neurites which, in the case of Neuro
      2a, could be blocked by the B subunit of cholera toxin (Ctx B) which binds
      specifically to GM1; however, the latter agent applied to NG108-15 cells proved
      neuritogenic and potentiated the effect of N'ase. With N18 cells, the combination
      was also neuritogenic as was Ctx B alone, whereas N'ase by itself had no effect.
      Neurite outgrowth correlated with influx of extracellular Ca2+, determined with
      fura-2. Treatment of NG108-15 and N18 cells with Ctx B alone caused modest but
      persistent elevation of intracellular Ca2+ while a more pronounced increase
      occurred with the combination Ctx B + N'ase. Treatment with N'ase alone also
      caused modest but prolonged elevation of intracellular Ca2+ in NG108-15 and Neuro
      2a but not N18; in the case of Neuro-2a this effect was blocked by Ctx B. Neuro
      2a and N18 thus possess 2 distinctly different mechanisms for neuritogenesis
      based on Ca2+ modulation by plasma membrane GM1, while NG108-15 cells show both
      capabilities. The neurites stimulated by N'ase + Ctx B treatment of N18 cells
      were shown to have axonal character, as previously demonstrated for NG108-15
      cells stimulated in this manner and for Neuro-2a cells stimulated by N'ase alone.

PMID- 10959490
TI  - Prevention of monensin-induced hyperpolarization in NG108-15 cells.
AB  - The NG 108-15 (neuroblastoma X glioma hybrid) cell line was used as an in vitro
      neuronal model to evaluate potential antagonists of the Na+-selective carboxylic
      ionophore monensin. Changes in membrane electrical characteristics induced by
      monensin with and without the simultaneous administration of antagonists were
      measured using intracellular microelectrode techniques. Bath application of
      monensin (3 microM) produced a hyperpolarization of approximately = 35 mV.
      Monensin also altered the generation of action potentials in response to
      electrical stimulation in 14 of 24 (58%) exposed cells, as evident in a partial
      or complete loss of action potentials or in an alteration of action potential
      waveform. The antagonists used were Na+-K+ pump inhibitor ouabain (1-3 microM),
      the Ca2+dependent K+ channel blocker quinine (3-30 microM) or drugs known to
      influence Ca2+ signaling in cells, i.e., trifluoperazine (3-10 microM), verapamil
      (1-10 microM) or chlorpromazine (3-30 microM). On a molar basis, ouabain was the
      most and trifluoperazine the least effective of the antagonists. Quinine,
      verapamil and chlorpromazine all prevented the development of the
      hyperpolarization in an approximate concentration-dependent manner. However, none
      of these drugs was able to block the effects of monensin on action potentials.
      Indeed, high concentrations of the antagonists that were most effective in
      preventing the hyperpolarization accentuated impairments in action potential
      generation and also reduced input resistance in many cells. Thus, none of these
      antagonists appears suitable for transition to in vivo antidotal protection
      studies.

PMID- 10959491
TI  - New benzodiazepines alter acetylcholinesterase and ATPDase activities.
AB  - This study examines the effect of new 1,5 benzodiazepines on acetylcholinesterase
      (AChE) and ATPDase (apyrase) activities from cerebral cortex of adult rats.
      Simultaneously, the effects of the classical 1,4-benzodiazepine on these enzymes
      were also studied for comparative purpose. The compounds 2-trichloromethyl-4
      phenyl-3H-1,5-benzodiazepin and 2-trichloromethyl-4(p-methyl-phenyl)-3H- 1,5
      benzodiazepin significantly inhibited acetylcholinesterase activity (p < 0.01)
      when tested in the range of 0.18-0.35 mM. The inhibition caused by these two new
      benzodiazepines was noncompetitive in nature. Similarly, at concentrations
      ranging from 0.063 to 0.25 mM, the 1,5 benzodiazepines inhibited ATP and ADP
      hydrolysis by synaptosomes from cerebral cortex (p < 0.01). However, the
      inhibition of nucleotide hydrolysis was uncompetitive in nature. Our results
      suggest that, although diazepam and the new benzodiazepines have chemical
      differences, they both presented an inhibitory effect on acetylcholinesterase and
      ATPDase activities.

PMID- 10959492
TI  - Differential glial and vascular expression of endothelins and their receptors in
      rat brain after neurotrauma.
AB  - We characterized the time-course, intensity of expression and cellular origin of
      components of the endothelin (ET) system in the rat brain after a standardized
      neurotrauma (cryogenic lesion of the parietal cortex). ET mRNAs were expressed at
      sham level after neurotrauma, whereas immunoreactivity for ET-1 was enhanced in
      glia and endothelium of the lesioned hemisphere and both hippocampi. The number
      of ET-3 positive mononuclear cells in the lesion perimeter increased starting at
      24h after injury. At 48h after neurotrauma, ET-receptor immunoreactivity was
      increased in astrocytes. In basilar artery endothelium, ETB-immunoreactivity was
      reduced at 48h to 72h recovering at 7 days whereas ETA-receptor and ET-peptide
      immunoreactivities were not altered. In summary, neurotrauma leads to a
      multicellular stimulation of endothelins in the brain along with a delayed
      selective loss of vascular ETB-receptors. These changes seem to be
      posttranscriptional and cell type specific. They favor vasoconstriction
      increasing the risk of late vasospasm and ischemia.

PMID- 10959493
TI  - Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain
      ischemia.
AB  - Application of single transient forebrain ischemia (ISC) in adult Wistar rats,
      lasting 2 or 10 min, caused inhibition of Na+,K+-ATPase activity in cytoplasmic
      membrane fractions of hippocampus and cerebral cortex immediately after the
      event. In the 2-min ISC group followed by 60 min of reperfusion, the enzyme
      inhibition was maintained in the cortex, while there was an increase in
      hippocampal enzyme activity; both effects were over 1 day after the event.
      However, in the 10-min ISC group enzyme inhibition had been maintained for 7 days
      in both cerebral structures. Interestingly, ischemic preconditioning (2-min plus
      10-min ISC, with a 24-hour interval in between) prevented the inhibitory effect
      of ischemia/reperfusion on Na+,K+-ATPase activity observed either after a single
      insult of 2 min or 10 min ischemia. We suggest that the maintenance of Na+,K+
      ATPase activity afforded by preconditioning be related to cellular
      neuroprotection.

PMID- 10959494
TI  - A model of inositol compartmentation in astrocytes based upon efflux kinetics and
      slow inositol depletion after uptake inhibition.
AB  - Intracellular compartmentation of inositol was demonstrated in primary cultures
      of mouse astrocytes, incubated in isotonic medium, by determination of efflux
      kinetics after "loading" with [3H]inositol. Three kinetically different
      compartments were delineated. The largest and most slowly exchanging compartment
      had a halflife of approximately 9 hr. This slow release leads to retention of a
      sizeable amount of pre-accumulated inositol in the tissue 24 hr after the onset
      of uptake inhibition, as confirmed by the observation that the inositol uptake
      inhibitor fucose caused a larger inhibition of unidirectional inositol uptake
      than of inositol pool size, measured as accumulated [3H]inositol after 24 hr of
      combined exposure to the inhibitor and the labeled isotope. Based upon the
      present observations and literature data, it is suggested that the large, slowly
      exchanging compartment is largely membrane-associated and participating in
      signaling via the phosphatidylinositide second messenger system, whereas inositol
      functioning as an osmolyte is distributed in the cytosol and located in one or
      both of the compartments showing a faster release.

PMID- 10959495
TI  - Hyperplastic changes and receptor status in the breast tissue of bodybuilders
      under anabolic-androgenic steroid stimulation.
AB  - Anabolic androgenic steroids (AAS) are misused by athletes to improve their
      physical performance. AAS with similar groups and configuration indicate that
      testosterone is the base of this ability to stimulate anabolic activity. The
      effect of these compounds on the breast tissue of males that consume them is a
      confirmation of its metabolic pathway. To confirm its hormonal effects, the
      status of estradiol and progesterone receptors (ER, PgR) status was determined in
      cytoplasmic and nuclear fractions (HRc, HRn) of 8 premalignant breast tissues
      from 8 bodybuilders (aged 21 to 45 years) under AAS stimulation. The control
      group included 5 males with benign disorders of the breast, but not due to AAS
      administration. The concentrations of ERc and ERn were significantly higher (p <
      .05) in males under AAS stimulation than in males without these. The
      concentrations of PgRc and PgRn do not differ between these two groups (p > .05)
      The benign breast disease is remarkably similar in female and male patients,
      suggesting a common origin. In the same way, the measurement of both HRc and HRn
      is necessary to accurately report receptor concentration.

PMID- 10959496
TI  - Absence of Y chromosome microdeletions involving the DAZ (deleted in azoospermia)
      and RBM (ribonucleic acid-binding motif) genes in patients with chordee without
      hypospadias.
AB  - The presence or absence of 33 DNA loci was investigated with a focus on the long
      arm of Y chromosome (Yq) interval 6 involving the DAZ and RBM genes, by means of
      a polymerase chain reaction strategy, in 10 patients with hypospadias. All
      patients did not show any of the 33 DNA loci. It would appear that chordee
      without hypospadias does not involve interval 6 of the Y chromosome.

PMID- 10959497
TI  - Detection of chromosome 15 deletion in Prader-Willi syndrome using fluorescence
      in situ hybridization.
AB  - Deletion of chromosome 15 was investigated in 6 patients with Prader-Willi
      syndrome (PWS) using chromosome and fluorescence in situ hybridization (FISH)
      analysis. Although chromosome analysis using G-banding methods revealed the
      deletion of 15q11-q13 in only 3 cases, staining by FISH using D15S11 and/or small
      nuclear ribonucleoprotein polypeptide N (SNRPN) probes detected chromosome 15
      deletion in all cases. It would appear that FISH analysis is an effective
      diagnostic test for the detection of chromosome 15 deletion in patients with PWS.

PMID- 10959498
TI  - Giant hydronephrosis of a duplex system associated with ureteral ectopia: a cause
      of retrograde ejaculation.
AB  - Retrograde ejaculation is an extremely rare complication of the ectopic ureter or
      ectopic ureterocele. In the literature, only two cases have been reported
      worldwide. In this article the authors describe a patient who has a completely
      duplicated collecting system with massive dilatation of the upper pole system,
      which has manifested as a huge abdominal and retroperitoneal mass, complicated by
      retrograde ejaculation.

PMID- 10959499
TI  - Successful treatment of azoospermia secondary to ejaculatory duct cyst.
AB  - Ejaculatory duct obstruction is considered a rare cause of infertility. Two cases
      are reported of an ejaculatory duct cyst with azoospermia preoperatively
      diagnosed by transrectal ultrasonography. The diagnosis of ejaculatory duct
      obstruction in one patient was confirmed by vasography with a combined iodinated
      contrast medium and methylene blue solution for radiological and direct
      visualization. Transrectal puncture and contrast filling of the cyst under the
      transrectal ultrasonographic guidance diagnosed the other patient. On the basis
      of these findings transurethral unroofing of the cyst was performed successfully.
      Transrectal ultrasonography facilitates evaluation and treatment of azoospermia
      caused by ejaculatory duct obstruction and may minimize the need for more
      invasive studies in such cases.

PMID- 10959500
TI  - Effect of sodium nitroprusside on mouse sperm migration in vitro.
AB  - In the present study the effect of sodium nitroprusside, a nitric oxide releaser,
      on mouse sperm motion behavior was examined. The number of sperm migrating in
      experimental plate to medium containing sodium nitroprusside in concentration 50
      nM was significantly higher than the number migrating to control. This effect was
      observed after 3 and 5 h of incubation, and it was not time dependent. The
      presence of sodium nitroprusside in higher concentrations did not cause any
      visible changes or decrease the migration of sperm. These effects were
      interpreted as chemokinesis but not chemotaxis of sperm induced by influence of
      sodium nitroprusside on sperm metabolism and motility.

PMID- 10959501
TI  - Secretion of glycosidases in human epididymal cell cultures.
AB  - The dynamics of glycosidase secretion was evaluated in human epididymal cell
      culture. Epithelial cells from caput, corpus, and cauda epididymis were isolated
      from tissue obtained from patients undergoing therapeutic orchidectomy due to
      prostatic carcinoma. The activities of alpha-glucosidase, N
      acetylglucosaminidase, beta-glucuronidase, and alpha-mannosidase were analyzed in
      conditioned culture media. Glycosidase activity was significantly higher in
      corpus and/or cauda than in caput epididymis. There was a time-dependent increase
      in enzyme activities that was maximal between 10 and 14 days of culture in all
      epididymal regions. Epididymal glycosidases are secreted by cultured epithelial
      cell from human epididymis with an increase toward the distal regions of this
      organ, which may be related to the dynamics of sperm maturation. Cultures from
      different epididymal regions may represent a valuable tool to study of human
      epididymal function.

PMID- 10959502
TI  - Conjugation of maturation-related wheat-germ-lectin-binding proteins to caput
      epididymal sperm in co-cultures with corpus epididymal epithelial cells of BALB/c
      mouse.
AB  - In BALB/c mice, two maturation-related wheat-germ-binding glycoproteins (GP-49
      and GP-83) are synthesized and secreted by corpus and cauda epididymis. A co
      culture technique was used to investigate these glycoproteins in principal cells
      of corpus epididymis and the conjugation of these molecules on caput sperm. The
      principal cells were recovered from corpus epididymides of 4-week-old mice and
      cultured in RPMI 1640 medium supplemented with 10% fetal calf serum. After
      culturing for 3-4 days, most cells revealed epithelial cell-specific keratins in
      immunofluorescent localization with monoclonal antibody. By electron microscopy,
      a prominent nucleolus with well-extended euchromatin was revealed in the nucleus
      and the cytoplasm contained multivesicular bodies, and a well-developed Golgi
      apparatus with endoplasmic reticulum. By SDS-PAGE, GP-83 and GP-49 were revealed
      in the cell extracts and cell culture supernatants after incubation with 35S
      methionine. Radiolabeled binding sites were also found on the surface of caput
      sperm co-cultured with the principal cells for 4 h in the presence of 35S
      methionine. WGA-binding glycoproteins may be synthesized and secreted by the
      principal cells of corpus epididymis and conjugated to caput sperm during the
      epididymal transit.

PMID- 10959503
TI  - Identification of maturation-related wheat-germ lectin-binding proteins in the
      culture of human corpus epididymal epithelial cells.
AB  - This study is designed to investigate the synthesis of maturation-related wheat
      germ agglutinin (WGA) binding glycoproteins in the human corpus epididymal
      epithelial cells by in vitro culture. Epithelial cells were isolated from the
      corpus of human epididymides and cultured with RPMI 1640 medium supplemented with
      10% fetal calf serum in type IV collagen-coated dishes at 37 degrees C. The
      epithelial nature, presence of fibroblasts, WGA-binding sites, and existence of
      GP-83 were determined by an indirect immunocytochemical and histochemical
      staining technique. Proteins in the cultured cells were analyzed by SDS-PAGE and
      autoradiography. After culturing for 10 days, the cells were shown to be positive
      with epithelial cell-specific keratins but devoid of fibroblasts. WGA-binding
      granules and positive binding sites of GP-83 were also detected in the cytoplasm.
      Immunoblots of cell extracts probed with the anti-GP-83 antibody from seminal
      fluid revealed the sperm maturation-related glycoprotein GP-83. The results
      indicate that WGA-binding proteins may be synthesized by the corpus epididymal
      epithelial cells of human and GP-83 may play an important role in sperm
      maturation. This culture model may be suitable for the investigation on the
      biosynthesis and physiology of human epididymal principal cells in vitro.

PMID- 10959504
TI  - Participation of DNA structure on sperm chromatin organization.
AB  - The in vitro interaction between purified bovine liver and sperm DNA with somatic
      histones, to form nucleosomes, and with bovine and salmon protamines were
      studied. DNAse or microccocal nuclease digestion of liver DNA-histone
      reassociated chromatin produced the expected polynucleosome type of fragments.
      Electrophoretic patterns of digested sperm-DNA nucleosomes were different.
      Micrococcal nuclease digestion produced mainly fragments smaller than 100 bp and
      some nucleosome-type particles. Under DNAse activity most of the products were
      smaller than 100 bp, indicating an increased susceptibility of the sperm DNA
      histone complexes to the hydrolytic activity of both nucleases, particularly
      toward DNAse I. This differential susceptibility was confirmed by sucrose
      gradient spectrophotometric analysis. Acridine orange (AO) staining of histone
      DNA reassociated nucleosomes showed significant differences in fluorescence
      intensity, sperm DNA-histone complexes being almost twice as fluorescent as liver
      DNA-histone complexes. On the contrary, liver DNA/protamine complexes stained
      with AO were consistently more fluorescent than sperm DNA-protamine complexes.
      Finally, no differences in either fluorescence intensity or spectra were observed
      when liver and sperm DNA were stained with AO after interaction with salmon
      protamines. The data suggest that sperm DNA has important structural
      characteristics that differentiates it from somatic DNA. These differences seem
      to be species specific and must surely play an important role on the
      determination of the dramatic sequence of that participates sperm chromatin
      organization.

PMID- 10959505
TI  - A randomized study comparing the effect of standard versus short incubation of
      sperm and oocyte on subsequent pregnancy and implantation rates following in
      vitro fertilization embryo transfer.
AB  - Some data suggest that some sperm are associated with a toxic product that lowers
      embryo implantation rates when these sperm come in contact with the zona
      pellucida. The possibility exists that shortening the incubation time could
      improve pregnancy rates. A randomized prospective study was initiated to evaluate
      pregnancy and implantation rates with transfer of embryos formed by conventional
      overnight vs short (2-h) co-incubation of sperm and oocytes. The clinical and
      viable pregnancy rates were 41 and 29% for conventional co-incubation versus 30
      and 30% for short co-incubation. Implantation rates were also similar (17.9 vs
      17.8%). Short incubation does not seem to impact any advantage over conventional
      co-incubation techniques in couples undergoing in vitro fertilization where the
      male factor is normal.

PMID- 10959506
TI  - Nomograms used to define the short-term treatment with PGE(1) in patients with
      intermittent claudication and critical ischemia. The ORACL.E (Occlusion
      Revascularization in the Atherosclerotic Critical Limb) Study Group. The European
      Study.
AB  - Infusional, cyclic PGE1 treatment is effective in patients with intermittent
      claudication and critical limb ischemia (CLI). One of the problems related to
      chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate
      the variations of clinical conditions due to treatment in order to establish the
      number of cycles per year or per period (in severe vascular disease reevaluation
      of patients should be more frequent) needed to achieve clinical improvement. In a
      preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with
      intermittent claudication (walking range from 0 to 500 m) and a group of 100
      patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years)
      the number of PGE1 cycles according to the short-term protocol (STP) needed to
      produce significant clinical improvement was preliminarily evaluated. Considering
      these preliminary observations, the investigators established a research plan
      useful to produce nomograms indicating the number of cycles of PGE1-STP per year
      needed to improve the clinical condition (both in intermittent claudication and
      CLI). A significant clinical improvement was arbitrarily defined as the increase
      of at least 35% in walking distance (on treadmill) and/or the disappearance of
      signs and symptoms of critical ischemia in 6 months of treatment in at least 75%
      of the treated patients. With consideration of the results obtained with the
      preliminary nomograms a larger validation of the nomograms is now advisable. A
      cost-effectiveness analysis is also useful to define the efficacy of treatment on
      the basis of its costs. The publication of this report in two angiological
      journals (Angeiologie and Angiology) will open the research on nomograms to all
      centers willing to collaborate to the study. The data are being collected in the
      ORACL.E database and will be analyzed within 12 months after the publication of
      this report.

PMID- 10959507
TI  - PGE(1) treatment of severe intermittent claudication (short-term versus long
      term, associated with exercise)--efficacy and costs in a 20-week, randomized
      trial.
AB  - The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of
      severe intermittent claudication was studied comparing a long-term treatment
      protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week
      study. The study included 980 patients (883 completed the study) with an average
      total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run
      in phase (no treatment) for both protocols. In LTP, phase 2 was the main
      treatment phase. In the LTP, treatment was performed with 2-hour infusions (60
      microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period)
      PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting
      3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was
      performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon
      40 microg; second day morning and afternoon 60 microg). The reduced dosage was
      used only at the first cycle (week 0) to evaluate tolerability or side effects.
      Full dosage (60 microg bid) was used for all other cycles. The same cycle was
      repeated at the beginning of weeks 4, 8, and 12. The observation period was
      between weeks 12 and 20. A treadmill test was performed at inclusion, at the
      beginning of each phase, and at the end of 20th week. A similar progressive
      physical training plan (based on walking) and a reduction in risk factors levels
      plan was used in both groups. Intention-to-treat analysis indicated an increase
      in walking distance, which improved at 4 weeks and at 20 weeks in the STP more
      than in the LTP group. At 4 weeks the variation (increase) in pain-free walking
      (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP
      group (p<0.05). At 4 weeks the variation (increase) in total walking distance
      (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group
      (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the
      LTP group vs 643% in the STP group (147% difference; p<0.02). The increase in TWD
      was 368% in the LTP group and 529% in the STP group (161% difference; p<0.02). In
      both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks,
      but results obtained with STP are better considering both walking distances. No
      serious drug-related side effects were observed. Local, mild adverse reactions
      were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average
      cost of LTP was 6,664 Euro; for STP the average costs was approximately 1,820 E.
      The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the
      LTP and 8.5 E with the STP (18% of the LTP cost; p<0.02). For an average 100%
      increase in walking distance the LTP cost was 1,989 E vs. 421 E with STP
      (p<0.02). Between-group analysis favors STP considering walking distance and
      costs. Results indicate good efficacy and tolerability of PGE, treatment. With
      STP less time is spent in infusion and more in the exercise program. STP reduces
      costs, speeds rehabilitation, and may be easily used in a larger number of
      nonspecialized units.

PMID- 10959508
TI  - Expanded polytetrafluoroethylene in external valvuloplasty for superficial or
      deep vein incompetence.
AB  - The authors evaluated the long-term safety of expanded polytetrafluoroethylene
      (ePTFE) implants used in external valvuloplasty for treatment of incompetence of
      the long saphenous and common and superficial femoral veins. During a 15-year
      period patients with superficial and/or deep venous disease and hypertension due
      to pure superficial or deep vein incompetence underwent an external valvuloplasty
      with ePTFE sutures, or an ePTFE cardiovascular patch placed as a sleeve around
      the incompetent vein segment, or an ePTFE tubular graft placed around the venous
      segment. Postoperative follow-up evaluations consisted of clinical examinations,
      high-resolution ultrasonography, and color duplex scanning, and a complete blood
      count performed at 1, 3 and 6 months, and repeated for at least 4 years, every 2
      years after the procedure. A total of 101 patients (38 men and 63 women; mean [+/
      sd] age, 44+/-12 years) underwent external valvuloplasty between January 1983
      and December 1998; 82 of them completed the 4-year follow-up. Forty of the 82
      patients had been operated on for superficial vein incompetence, 42 for deep vein
      incompetence. Overall, the mean follow-up time was 7.8+/-3.6 years (range, 4 to
      13). There were no infections, thromboses,foreign-body reactions to the ePTFE
      implants, or other prosthesis-related complications requiring explantation. One
      granuloma (noninfected) developed in association with a tubular ePTFE implant
      around a long saphenous vein, but it did not necessitate implant removal. Seven
      patients required (at least after 4 years) a second procedure for recurrent or
      new venous incompetence. Therefore, in this observational study, ePTFE implants
      used to treat or correct venous incompetence were well tolerated on a long-term
      basis.

PMID- 10959509
TI  - Tissue response to an expanded polytetrafluoroethylene external valve support
      device: a histologic study in dogs.
AB  - Expanded polytetrafluoroethylene (ePTFE) external valve support devices (EVS)
      have been used successfully in patients to restore valve function in leg veins
      with incompetent valves when incompetence is due to dilatation of the vein walls
      or elongation of the valve leaflet edges. To assess tissue response to these
      devices, the authors implanted 12 of them in dogs, wrapping the devices around
      veins in the head and neck. The dogs recovered from the implantation procedure
      uneventfully, and the veins remained patent on color flow Doppler scanning. Gross
      and histologic evaluations of vein segments and attached EVS devices after
      sacrifice of the dogs 30 days postoperatively showed that the ePTFE devices did
      not affect vein patency or the cellular composition or architecture of vein
      walls. There were no adverse tissue reactions to the EVS and no thrombus
      formation in the veins to which the EVS had been applied. Tissue attachment to
      the EVS was apparent in all specimens. These histologic results support clinical
      experiences indicating that the ePTFE EVS device is safe to use in external
      valvuloplasty for the treatment of venous incompetence.

PMID- 10959510
TI  - Superficial vein valve repair with a new external valve support (EVS). The IMES
      (International Multicenter EVS Study).
AB  - The aim of this international multicenter trial was to evaluate the effects of a
      new surgical device (Gore External Valve Support-EVS) and technique for external
      valvuloplasty of the long saphenous vein (LSV). Patients with superficial venous
      disease and venous hypertension due to pure superficial venous incompetence were
      randomized into two treatment groups, the first treated with "conventional
      treatment" (ligation or stripping) and the second with external valvuloplasty
      with the EVS. Patients with uncomplicated varicose veins within the age range of
      35-65 years were included. Incompetence with presence of functional cusps at the
      saphenofemoral junction (SFJ), with vein dilatation were the main inclusion
      criteria. The EVS comprised of a GORE-TEX patch material (including a nitinol
      frame) that is placed around the vein, producing a reduction in the caliber of
      the vein. Also the vein section becomes elliptical. These combined actions are
      aimed to reduce incompetence, allowing a better closure of the cusps. The EVS was
      placed at the SFJ after limited dissection of the vein and ligation of
      collaterals. The procedure was randomized as an alternative to simple ligation or
      stripping (according with the procedure commonly used in the center). The
      associated ligation of distal incompetent veins was allowed. The main outcome
      measures of the study were evaluated by color-duplex (morphologic findings and
      evaluation of reflux) and with ambulatory venous pressure (AVP) or air
      plethysmography (APG). Main endpoints of the first year of the study and main
      subject of this report (mainly concerning safety within the first year of follow
      up) were considered presence/absence of reflux; patency of the veins;
      mobility/function of vein cusps; occurrence of thrombosis; tolerability of the
      device; and increased complexity and operating time needed for the EVS. At 1 year
      30 patients had been randomized (14 EVS implanted, 16 controls). Reflux was
      absent in all EVS patients, all treated veins were patent, and all cusps were
      mobile. No thrombosis had been observed and the tolerability of the device was
      very good. The increased complexity required by placing the EVS was limited (5-12
      minutes more). In conclusion results of the first year show efficacy and
      tolerability of the EVS. In selected patients (superficial LSV incompetence,
      reflux-dilatation, functional SFJ cusps, incompetence mainly due to enlargement
      of the vein), the EVS could be an effective alternative to "destructive" ligation
      and/or stripping of the vein. Prolonged follow-up will indicate the clinical
      potentials of the EVS.

PMID- 10959511
TI  - Pressure and microcirculatory effects of treatment with lercanidipine in
      hypertensive patients and in vascular patients with hypertension.
AB  - The aim of this study was to evaluate the macrocirculatory and microcirculatory
      effects of treatment with lercanidipine, a new antihypertensive agent acting both
      on blood pressure and microcirculation in patients with moderate essential
      hypertension and without vascular disease and in patient with hypertension and
      vascular disease. In hypertensive subjects target-organ damage associated with
      high blood pressure may now be objectively documented by noninvasive tests. These
      alterations constitute a model to evaluate not only the pressure effects of
      antihypertensive treatment but also the normalization of the peripheral
      microcirculatory network. With color duplex scanning, flow velocity in the
      central retinal artery and retinal flow velocity can be measured and with use of
      laser-Doppler-flowmetry, it is also possible to evaluate microcirculation
      alterations in hypertensive subjects. These evaluation methods are completely
      noninvasive and may be used to assess the microcirculatory effects of
      antihypertensive drugs.

PMID- 10959512
TI  - San Valentino epidemiologic vascular project.

PMID- 10959513
TI  - Effects of shock waves on the microcirculation in critical limb ischemia (CLI) (8
      week study).
AB  - Shock waves (SWs) are used to control and decrease pain in several clinical
      conditions (e.g., painful elbow and shoulder, etc). This clinical effect may be
      due to cellular stunning of the tissues (particularly nervous components) in the
      area treated with SW. It may also be the consequence of unknown metabolic actions
      on tissues, which may include changes in cellular permeability and the liberation
      of proteins and mediators locally acting on pain and nerve endings. The aim of
      this study was to evaluate the reduction in pain and the microcirculation
      improvement induced by SWs treatment in an 8-week study in patients with chronic
      limb ischemia (CLI). Patients with CLI (15 with rest pain only and 15 with rest
      pain and limited distal necrosis) were included. The treatment was based on a 30
      minute SWs session, three times weekly for 2 weeks. Clinical and microcirculatory
      evaluation were performed with laser Doppler Po2 and Pco2 measurements. Pain was
      measured with an analogue scale line. A Minilith SL1 (Storz Medical, Switzerland)
      litotriptor was used. The parabolic reflector is coupled to the skin with a
      silicon water cushion. Focal pressure was adjusted between 6 and 70 Mpa in eight
      steps. The energy flux density was variable from 0.03 to 0.5 mJ/mm2. Focal
      diameter and distance were defined (depth of target within the patient's foot of
      about 70 mm). The coded intensity used in this study was between 6 and 8 and the
      application time was 20 min (at four impulses per second). Twenty-eight of the 30
      patients with CLI (15 with rest pain only and 13 with necrosis) completed the
      study. The treatment was well tolerated. Blood pressure was unchanged after 8
      weeks while the increase in laser Doppler flux was significant (p<0.05) (at all
      measurements after treatment). The ORACLE score at 1 and 8 weeks was decreased
      (p<0.05). The same trend was observed with the analogue scale line for pain
      (p<0.05). PO2 increased (p<0.05) and Pco2 decreased (p<0.05). Tibial pressure did
      not change. All patients observed an increase in their subjective pain-free
      walking distance. The improvement was still present after 8 weeks. In a separate
      subset of 37 patients (mean age 60+/-9 years; males) with CLI, a SWs dose-finding
      evaluation was performed. Flux changes were measured at the dorsum of the foot.
      Three treatment plans were used: (a) 20-minute SW treatment only once; (b) 20
      minute SWs treatment every 2 days for 1 week; (c) 20 minutes every day for 1
      week. Treatments were well tolerated. A different increase in flux was observed
      on the basis of different treatments. Flux variations generally indicated that
      increased SWs dosage was associated with proportional flux increase. Flux
      improvement was still present after 4 weeks. SWs treatment in CLI produced
      changes both in the microcirculation and on pain. These preliminary results are
      comforting and open new research options to be explored in the near future.

PMID- 10959514
TI  - Reversing heart disease in the new millennium--the Fleming unified theory.
AB  - Nineteen people without prior history of documented heart disease were studied
      for 8 months to determine the effect of treatment based on an immunologic unified
      theory of vascular disease. Subjects underwent myocardial perfusion imaging to
      quantify the extent and severity of coronary artery disease, along with
      assessment of wall motion abnormalities and ejection fraction by both nuclear and
      echocardiographic methods. These tests were repeated at the end of the study.
      Treatment consisted of dietary changes, treatment of cholesterol, triglycerides,
      homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection.
      Patients who followed the dietary recommendations demonstrated statistically
      reduced disease in all three major coronary arteries, whereas those individuals
      who followed high-protein diets demonstrated statistically greater levels of
      disease.

PMID- 10959515
TI  - Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: a
      review. DUMQOL (DUtch Mononitrate Quality of Life) Study Group.
AB  - Since the first publication of isosorbide mononitrate 30% immediate-release 70%
      sustained-release (IR-SR) formulation in 1985, a considerable body of literature
      concerning its clinical efficacy and safety has become available. Theoretically,
      the formulation has the advantage over conventional isosorbide mononitrate or
      dinitrate (ISMN/ISDN) that it has a simpler and more predictable pharmacokinetic
      profile. The objectives of this paper are to review published data so far and to
      see whether the theoretical advantages translate into better clinical
      effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a
      rapid onset of action (30 minutes), and effects are evident for up to 17 hours.
      2. The antianginal effects of once-daily isosorbide mononitrate IR-SR increased
      with increasing dosages, were generally larger than those of either placebo or
      equipotent doses of conventional ISMN/ISDN, and were somewhat larger than those
      of the beta blocker bupranolol. The effects were generally similar to those of
      sustained release nifedipine. 3. Patients showed significantly greater
      improvement in some quality-of-life indices with once-daily isosorbide
      mononitrate IR-SR than with twice or three times daily regimens of conventional
      ISMN/ISDN. This was particularly so with mobility, psychological distress, and
      life satisfaction indices. 4. Tolerance did not develop after 13 months of once
      daily isosorbide dinitrate IR-SR. No rebound increase in incidence of ischemic
      episodes was observed after discontinuation of treatment. 5. Long-term efficacy
      data both of isosorbide mononitrate IR-SR and of conventional ISMN/ISDN are
      limited so far. Large studies in patients with angina pectoris and patients with
      heart failure addressing long-term effects are ongoing, and some of the data will
      be completed within the next months. Isosorbide mononitrate IR-SR has a rapid
      onset of action and has been shown to be clinically efficient and, in addition,
      to be more so than conventional ISMN / ISDN. Nitrate tolerance with continued use
      of the formulation has not yet been reported. Long-term effects on morbidity and
      mortality are currently being assessed.

PMID- 10959516
TI  - Association between mitral annulus calcification and peripheral arterial
      atherosclerotic disease.
AB  - The authors previously demonstrated a significant association between the
      presence of mitral annulus calcification (MAC) and aortic atheroma, carotid
      atherosclerotic disease, and coronary artery disease. The present study was
      designed to determine whether an association exists between MAC and peripheral
      arterial atherosclerotic disease. Of the 805 patients in whom the diagnosis of
      MAC was made by transthoracic echocardiography between 1995 and 1997, 77 patients
      (40 men and 37 women; mean age, 73.1 +/- 11.4 years; range, 44-90 years)
      underwent peripheral arterial testing for various indications, and comprised the
      study group. They were compared with 58 age-matched and sex-matched patients
      without MAC (30 men and 28 women; mean age, 73.2 +/- 11.8 years; range, 31-93
      years) who underwent peripheral arterial testing during the same period for the
      same indications (control group). MAC was defined as a dense, localized, highly
      reflective area at the base of the posterior mitral leaflet detected by
      transthoracic echocardiography. An ankle/brachial systolic pressure index (ABI)
      was calculated by dividing the higher dorsalis pedis or posterior tibial Doppler
      derived pressures by the higher of the 2 upper extremity systolic pressures. ABI
      was graded as follows: normal > or = 1, abnormal < 1, mild 0.71 to 0.99, moderate
      0.41 to 0.7, and severe < or = 0.4. No differences were found between the groups
      in indications for referral for peripheral arterial testing and in risk factors
      for atherosclerosis except for hypertension, which was found to be significantly
      more prevalent in the study group (66% vs 41%, p = 0.004). The study group
      included 151 limbs, and the control group included 113 limbs. The mean ABI was
      significantly lower for all limbs in the MAC group (0.56 +/- 0.27 vs 0.87 +/-
      0.24, p = 0.0001), abnormal ABI < 1 (94% vs 68%, p = 0.001), moderate peripheral
      arterial disease (44% vs 25%, p = 0.001), and a severe disease (27% vs 1%, p =
      0.001). Of the 77 patients with MAC, 73 (95%) had a disease (right and/or left
      limbs) compared with 40 of 58 (69%) in the control group (p = 0.001). Bilateral
      disease (Doppler index < 1 for both right and left limbs), and severe bilateral
      disease (Doppler index < or = 0.4 for both right and left limb) were also found
      to be significantly more prevalent in the MAC group (87% vs 60%, p = 0.001; and
      12% vs 0%, p = 0.007, respectively). There is a significant association between
      the presence of MAC and peripheral arterial disease. This information strengthens
      our hypothesis that MAC may be an important marker for generalized vascular
      atherosclerotic disease.

PMID- 10959517
TI  - Immediate and long-term results comparing coronary versus biliary tubular-slotted
      stents to treat old obstructed saphenous vein grafts.
AB  - Stenting of old obstructed saphenous vein grafts improves immediate angiographic
      results and long-term clinical outcome compared to standard balloon angioplasty.
      Comparison of results and long-term clinical outcome between different types of
      stents in the treatment of vein graft disease is scarce. The authors studied two
      matched groups of 33 patients each, receiving either coronary or biliary tubular
      slotted stents in old vein graft lesions to compare immediate results and long
      term clinical outcome. Patients in the two groups were matched for age and left
      ventricular function. Baseline angiographic characteristics, the minimal luminal
      diameter (MLD) (0.68 +/- 0.56 mm vs 0.61 +/- 0.51 mm, p = 0.9), and diameter
      stenosis (DS) (81 +/- 14% vs 82 +/- 15%) were similar between the groups. After
      stenting, the MLD (3.15 +/- 0.65 mm vs 3.37 +/- 0.63 mm, p = 0.9) and residual
      stenosis (-7 +/- 19% vs -11 +/- 21%) were also similar. The in-hospital major
      complications (myocardial infarction and death) (one vs eight, p = 0.01) and the
      combination of major and minor (bleeding and vascular) complications (eight vs
      17, p = 0.02) were higher in the biliary stent group. At long-term follow-up,
      both groups of patients had high but comparable rates of major cardiovascular
      events (39% vs 45%, p = 0.62). Kaplan-Meier event-free survival analysis did not
      show any statistically significant difference in event-free survival (log-rank
      statistic 0.98). The authors conclude that patients receiving biliary stents had
      higher rates of immediate minor and major complications, but at long-term follow
      up, major cardiovascular event rates were comparable between the two groups of
      patients.

PMID- 10959518
TI  - Changing features of stent-supported primary angioplasty for acute myocardial
      infarction: impact of new flexible stents.
AB  - Although primary coronary stenting for acute myocardial infarction (AMI) has been
      reported to be superior to primary percutaneous transluminal coronary angioplasty
      (PTCA), cautious entry criteria resulted in low-risk populations in these
      studies. This study was undertaken to delineate factors that have not been
      clarified by randomized multicenter studies and is based on the results of stent
      supported primary PTCA for AMI using second-generation new stents. In 1994-1998,
      355 AMI patients were studied < 12 hours after onset. The patients were divided
      into two groups: group 1 (n = 175) was treated in 1994-1996 and group 2 (n = 180)
      in 1997-1998. In group 1, bailout stenting was performed in 17% of the patients
      for acute coronary dissection or occlusion with use of Palmaz-Schatz stents. In
      group 2, stenting was performed in 62% of the patients for suboptimal coronary
      dilatation and dissection or occlusion, using second-generation flexible stents
      with excellent radial force in 65% of them (Multilink, GFX, and NIR). In-hospital
      death and reinfarction occurred in 7.4% of group 1 and 5.0% of group 2 patients,
      and follow-up death and reinfarction in 4.0% of group 1 and 0.6% of group 2
      patients (p < 0.05). In-hospital target vessel revascularization was performed in
      8.6% of group 1 and 3.3% of group 2 patients (p < 0.05), and follow-up target
      vessel revascularization in 21.1% of group 1 and 11.7% of group 2 patients
      (p<0.02). Thus, the total adverse clinical event rates were 36.0% in group 1 and
      18.3% in group 2 (p < 0.01). In conclusion, outcomes of stent-supported coronary
      intervention in nonselected AMI patients have improved along with the
      availability of second-generation flexible stents, approaching the outcomes of
      primary stent studies in highly selected patients.

PMID- 10959519
TI  - Renal vascular resistance in essential hypertension: duplex-Doppler
      ultrasonographic evaluation.
AB  - Duplex Doppler ultrasonography has been validated as a noninvasive method to
      evaluate hemodynamic features of renal blood flow in renal and intrarenal
      arteries in patients with various renal diseases. The significance of duplex
      Doppler sonography in the evaluation of renal vascular resistance in essential
      hypertension has not yet been clearly determined. The aim of the present study
      was to evaluate the renal vascular resistance in patients with essential
      hypertension by measuring intrarenal arterial resistance (RI) and to correlate RI
      with renal functional tests and other clinical and laboratory data. Duplex
      Doppler ultrasonography was used to measure RIs in intrarenal arteries in 128
      patients with essential hypertension and 61 age-matched normotensive control
      examinees. The renal vascular resistance index (RI) was determined by use of
      Doppler ultrasound. Hypertension was classified according to the 1997 Joint
      National Committee Guidelines (JNC-VI). Mean RI in hypertensive patients was 0.66
      +/- 0.05 (+/- sd) and in healthy controls 0.60 +/- 0.03 (+/- sd) (p = 0.0001). RI
      correlated significantly with patient's age (r = 0.577, p = 0.001), duration of
      hypertension (r = 0.335, p= 0.001), stage of hypertension according to the JNC-VI
      classification (r = 0.315, p = 0.006), creatinine clearance (r = -0.383, p =
      0.001), systolic blood pressure (SBP, r = 0.41, p = 0.001) and mean blood
      pressure (MBP, r = 0.30, p = 0.002). RI values did not correlate significantly
      with plasma renin concentration (r = -0.198 NS), diastolic blood pressure (DBP, r
      = 0.17, p = 0.06), and cardiac pulse (r = -0.10, p = 0.16). Multiple regression
      analysis showed that independent variables for RI were the patient's age
      (multiple R = 0.53, signif. F = 0.001) and systolic blood pressure (multiple R =
      0.57, signif. F = 0.03). The renal Doppler resistance index (RI) is increased in
      essential hypertension and it correlates with renal functional tests as well as
      with patient's age, duration of hypertension, with a stage of hypertension
      according to the JNC-VI classification, and with systolic and mean blood
      pressure. The increased renal vascular resistance (RI) in hypertensive patients
      could be a sign of developing hypertensive nephrosclerosis and consequently renal
      failure. The utilization of the renal vascular resistance index (RI), provides a
      new noninvasive parameter in the followup of patients with essential
      hypertension.

PMID- 10959520
TI  - T wave alternans can decrease after coronary revascularization.
AB  - Clinical observations and animal experiments indicate that T wave alternans (TWA)
      is associated with an increased propensity for ventricular fibrillation, and thus
      it may be considered as a noninvasive marker of life-threatening ventricular
      arrhythmias. There is substantial evidence indicating that TWA is an intrinsic
      property of ischemic myocardium. This study was performed to determine the role
      of percutaneous transluminal coronary angioplasty (PTCA)-induced myocardial
      ischemia in the development of TWA and the effects of revascularization. The
      authors recorded bipolar X, Y, and Z leads of 111 consecutive patients (mean age:
      56 years) undergoing PTCA before, during, and 24 hours after the procedure. T
      wave alternans signal was calculated in 97 patients (43 left anterior descending,
      26 right coronary artery, and 28 circumflex or major obtuse margin branch) by
      fast Fourier transformation technique after signal processing. Twenty-four hours
      after the procedure, the mean and peak X, Y, and Z values for TWA had all been
      significantly reduced from baseline and during balloon inflation (p<0.01). The
      findings point out that induced ischemia could be a trigger for T wave alternans,
      and successful revascularization can reduce alternans.

PMID- 10959522
TI  - A case with severe rhabdomyolysis and renal failure associated with cerivastatin
      gemfibrozil combination therapy--a case report.
AB  - Gemfibrozil-statin combination therapy is a well-known risk factor for myopathy
      and rhabdomyolysis. Cerivastatin is a currently available statin with dual
      elimination; it is therefore expected to cause less drug-drug interaction. This
      case is the second reported case with severe rhabdomyolysis caused by
      cerivastatin-gemfibrozil combination. Moreover, in this case, the rhabdomyolysis
      was more severe and caused severe renal failure and death. The authors discuss
      how these drugs cause rhabdomyolysis and how rhabdomyolysis can cause renal
      failure.

PMID- 10959521
TI  - Myocardial infarction with acute insulin poisoning--a case report.
AB  - A 36-year-old woman without overt coronary risk factors was admitted to hospital
      with coma about 9 hours after mass self-injection of insulin (1,500 units).
      Laboratory investigation revealed severe hypoglycemia and hyperinsulinemia.
      During the treatment of her hypoglycemia, circulatory collapse occurred. The ECG,
      echocardiogram, and elevation in troponin T suggested a diagnosis of myocardial
      infarction. Although the patient became apallic and developed systemic spasticity
      due to hypoglycemic brain damage, her hemodynamics improved with supportive care
      alone. Coronary angiography and myocardial scintigraphy performed later
      demonstrated a broad area of myocardial damage despite intact coronary artery
      circulation. The authors hypothesize that temporary coronary arterial narrowing
      or coronary arterial vasospasm induced by severe hyperinsulinemia contributed to
      the pathogenesis of the myocardial infarction. The possibility of myocardial
      infarction should be considered in patients with acute insulin poisoning.

PMID- 10959523
TI  - Transoral carotid ultrasonographic findings in internal carotid artery dissection
      -a case report.
AB  - Transoral carotid ultrasonography (TOCU) is a new method to evaluate the far
      distal segment of the extracranial internal carotid artery (ICA) and may be
      superior to conventional carotid ultrasonography in evaluating ICA dissection.
      The authors report on the use of TOCU in detecting early stage ICA dissection.

PMID- 10959524
TI  - Haloperidol reinstates latent inhibition impaired by hippocampal lesions: data
      and theory.
AB  - The effect of haloperidol administration on the impairment of latent inhibition
      produced by aspirative lesions of the hippocampus was examined in the rat
      eyeblink response preparation. During the preexposure phase, rats with
      hippocampal or control lesions were either exposed to a tone or allowed to sit in
      the training apparatus. During the conditioning phase, the tone was paired with
      an airpuff to the eye after the rats were injected with either saline or
      haloperidol. Although saline-injected rats with hippocampal lesions did not show
      latent inhibition, the phenomenon was reinstated in rats that received
      haloperidol injections. A possible locus of the interaction between hippocampal
      lesions and haloperidol is the nucleus accumbens. The reported data are well
      described by a neural network model of classical conditioning. This study
      contributes to the understanding of the neurophysiology of latent inhibition as
      well as the neuropsychological bases of schizophrenia.

PMID- 10959525
TI  - Fear conditioning and brain activity: a positron emission tomography study in
      humans.
AB  - Regional cerebral blood flow (rCBF) was measured with H2 (15)O positron emission
      tomography in 8 healthy women before and after fear conditioning (i.e., paired
      shocks) and unpaired shocks to videotape cues. Conditioning was supported by
      enhanced peripheral nervous system recordings and subjective ratings. Fear
      conditioning increased rCBF in the central gray of the midbrain; bilaterally in
      the hypothalamus, the thalamus, and the left striatum; and in the right and left
      anterior cingulate and right prefrontal cortices. Regional CBF was attenuated
      bilaterally in the right and left prefrontal, temporal (including the amygdala),
      parietal, and occipital cortices, and in the left orbitofrontal cortex. When
      compared with unpaired shock presentations, fear conditioning resulted in
      elevated rCBF in the left cerebellum. Hence, in the present paradigm, only neural
      activity in the left cerebellum solely reflected processes associated with true
      Pavlovian conditioning.

PMID- 10959526
TI  - Associative fear conditioning of enkephalin mRNA levels in central amygdalar
      neurons.
AB  - The central nucleus of the amygdala (CEA) is required for the expression of
      learned fear responses. This study used in situ hybridization to show that mRNA
      levels of the neuropeptide enkephalin are increased in CEA neurons after rats are
      placed in an environment that they associate with an unpleasant experience. In
      contrast, mRNA levels of another neuropeptide, corticotropin releasing hormone,
      do not change under the same conditions in the CEA of the same rats. Conditioned
      neuropeptide levels in amygdalar circuits may act as a reversible "gain control"
      for long-term modulation of subsequent fear responses.

PMID- 10959527
TI  - Dissociation of place and cue learning by telencephalic ablation in goldfish.
AB  - This study examined the spatial strategies used by goldfish (Carassius auratus)
      to find a goal in a 4-arm maze and the involvement of the telencephalon in this
      spatial learning. Intact and telencephalon-ablated goldfish were trained to find
      food in an arm placed in a constant room location and signaled by a local visual
      cue (mixed place-cue procedure). Both groups learned the task, but they used
      different learning strategies. Telencephalon-ablated goldfish learned the task
      more quickly and made fewer errors to criterion than controls. Probe trials
      revealed that intact goldfish could use either a place or a cue strategy, whereas
      telencephalon-ablated goldfish learned only a cue strategy. The results offer
      additional evidence that place and cue learning in fish are subserved by
      different neural substrates and that the telencephalon of the teleost fish, or
      some unspecified structure within it, is important for spatial learning and
      memory in a manner similar to the hippocampus of mammals and birds.

PMID- 10959528
TI  - Spatial working memory is independent of hippocampal CA1 long-term potentiation
      in rats.
AB  - This study investigated the relationship between spatial working memory and
      hippocampal long-term potentiation (LTP) using the allocentric place
      discrimination task (APDT) in rats, in which the selection accuracy is a good
      index for spatial working memory. Either the selective M1 muscarinic receptor
      antagonist pirenzepine (50 microg) or the choline uptake inhibitor hemicholinium
      3 (5 microg) impaired APDT selection accuracy, but neither affected the induction
      of LTP in the hippocampal CA1 region in anesthetized rats. In contrast, the
      selective N-methyl-D-aspartate receptor antagonist D-amino-5-phosphonopentanoate
      (200 nmol) did not impair APDT selection accuracy but completely blocked
      hippocampal CA1 LTP. These results suggest that spatial working memory is
      independent of hippocampal CA1 LTP and that the central cholinergic system is
      involved in spatial working memory, but not through the modulation of hippocampal
      CAI LTP.

PMID- 10959529
TI  - Glutamatergic influences on the nucleus paragigantocellularis: contribution to
      performance in avoidance and spatial memory tasks.
AB  - Stimulation of the locus coeruleus (LC) and the subsequent release of
      norepinephrine contribute to memory consolidation processes. Excitatory input to
      the LC is derived primarily from neurons in the nucleus paragigantocellularis
      (PGi). The authors examined the effects of activating the pathway between PGi and
      the LC on memory. Rats received vehicle or the excitatory amino acid glutamate
      (25, 50, or 100 nmol/0.5 microl) into PGi after training in an inhibitory
      avoidance (IA) or delayed matching-to-sample (DMS) task. Rats given the 100-nmol
      dose had significantly longer retention latencies on a 48-hr IA retention test.
      Rats treated with the 50- or 100-nmol dose made significantly more correct
      responses than controls on an 18-hr DMS retention test. Results suggest that
      encoding and storage of memory for emotional and spatial events may be enhanced
      by activation of neuronal circuits afferent to the LC.

PMID- 10959530
TI  - Modification of a weak learning experience by memory retrieval in the day-old
      chick.
AB  - Activation of memory retrieval after weak learning (WL), during either the short-
      or intermediate-term stages of memory in day-old chickens, resulted in the
      strengthening of the memory to levels normally associated with strong learning.
      Administration of the calcium channel antagonist lanthanum chloride, the
      glutamate receptor agonist monosodium glutamate, or the N-methyl-D-aspartate
      glutamatergic receptor antagonist AP5 prevented strengthening of a WL memory by
      reminder-activated memory retrieval. The results of this study are discussed in
      light of our recent findings suggesting two phases of memory retrieval in the day
      old chick. The results are consistent with the proposition that a memory
      undergoing the processes of formation may be modified to include information
      gleaned at the time of memory retrieval and that a second phase of memory
      retrieval may be responsible for such modification.

PMID- 10959531
TI  - Potentiation of conditioned freezing following dorsomedial prefrontal cortex
      lesions does not interfere with fear reduction in mice.
AB  - In Experiment 1, an auditory conditioned stimulus (CS) was paired with footshock,
      except when it was preceded by another stimulus (a visual conditioned inhibitor
      [CI]). After conditioning, all mice displayed less CS-evoked freezing when the CI
      CS compound was presented than when the CS was presented alone. However, lesions
      of the dorsomedial prefrontal cortex (dmPFC) potentiated CS-evoked freezing on
      each of the 2 sessions (i.e., CI CS and CS alone). In Experiment 2, mice were
      submitted to fear extinction (CS-alone presentation for 3 days). Lesioned mice
      exhibited a higher level of freezing behavior than controls on each of the 3
      sessions. However, lesioned mice and controls displayed the same rate of
      reduction of freezing over the 3 days of extinction. These data in mice support
      previous studies in rats, which suggests that the dmPFC is not critical for
      either conditioned inhibition or extinction of acquired freezing behavior.

PMID- 10959532
TI  - Prenatal cocaine exposure impairs selective attention: evidence from serial
      reversal and extradimensional shift tasks.
AB  - This study assessed the effects of prenatal cocaine exposure on cognitive
      functioning, using an intravenous (IV) rodent model that closely mimics the
      pharmacokinetics seen in humans after smoking or IV injection and that avoids
      maternal stress and undernutrition. Cocaine-exposed males were significantly
      impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning
      task. Both male and female cocaine-exposed rats were significantly impaired on
      extradimensional shift tasks that required shifting from olfactory to spatial
      cues; however, they showed no impairment when required to shift from spatial to
      olfactory cues. In-depth analyses of discrete learning phases implicated
      deficient selective attention as the basis of impairment in both tasks. These
      data provide clear evidence that prenatal cocaine exposure produces long-lasting
      cognitive dysfunction, but they also underscore the specificity of the
      impairment.

PMID- 10959533
TI  - A comparative MRI study of the relationship between neuroanatomical asymmetry and
      interhemispheric connectivity in primates: implication for the evolution of
      functional asymmetries.
AB  - The authors tested the theory that hemispheric specialization evolved as a
      consequence of reduced interhemispheric connectivity by examining whether
      neuroanatomical asymmetries were associated with variation in the ratio of corpus
      callosum size to brain volume (CC:VOL) and to neocortical surface area (CC:NEO)
      in human and nonhuman primates. Magnetic resonance images were collected in a
      sample of 45 primates including 8 New World monkeys, 10 Old World monkeys, 4
      lesser apes, 17 great apes, and 6 humans. CC:VOL and CC:NEO were determined and
      correlated with measures of brain asymmetry. The results indicate that brain
      asymmetry significantly predicted CC:VOL and CC:NEO. Subsequent analyses revealed
      that species variation in functional asymmetries in the form of handedness are
      also inversely related to CC:NEO. Taken together, these results support the
      hypothesis that leftward brain asymmetries may have evolved as a consequence of
      reduced interhemispheric connectivity.

PMID- 10959534
TI  - Posttraining lesions of the amygdala interfere with fear-potentiated startle to
      both visual and auditory conditioned stimuli in C57BL/6J mice.
AB  - The fear-potentiated startle paradigm has been used with great success to examine
      conditioned fear in both rats and humans. The purpose of the present experiment
      was to extend the authors' previous findings and further validate the fear
      potentiated startle paradigm in mice. In Experiments 1 and 2, C57BL/6J mice were
      given Pavlovian fear conditioning with either an auditory or a visual conditioned
      stimulus. Similar to data collected with rats, fear-potentiated startle was
      observed for both stimulus modalities. In Experiment 3, posttraining lesions of
      the amygdala disrupted fear-potentiated startle in both conditioned stimulus
      modalities. These data are consistent with amygdala lesion studies in rats and
      suggest that fear-potentiated startle in mice requires an intact amygdala.
      Together, these results extend the authors' previous results and provide the
      basis for using this well-understood behavioral paradigm for examining the
      molecular mechanisms of conditioned fear in transgenic and knockout mice.

PMID- 10959535
TI  - Forebrain lesions differentially affect drinking elicited by dipsogenic
      challenges and injections of muscimol into the median raphe nucleus.
AB  - Injections of muscimol into the median raphe nucleus (MR) elicit intense drinking
      in normally hydrated rats. To determine whether this response is dependent on
      forebrain systems mediating other aspects of water intake, the authors examined
      the effects of lesions of the subfornical organ (SFO), median preoptic nucleus
      (MnPO), lateral preoptic area (LPO), or lateral hypothalamus (LH) on the
      drinking. Lesions of the SFO or LH attenuated muscimol-elicited drinking, whereas
      lesions of the MnPO or LPO increased water intake after the treatment. All of the
      lesion groups showed a deficit in drinking to injections of polyethylene glycol
      and at least one of the doses of hypertonic saline. Only the SFO- and LH-lesioned
      groups showed a suppression of drinking to systemic injections of angiotensin II,
      suggesting that the drinking elicited by intra-MR injections of muscimol may
      involve changes in the central circuits mediating angiotensin-induced drinking.

PMID- 10959536
TI  - Dopamine release in the medial preoptic area of female rats in response to
      hormonal manipulation and sexual activity.
AB  - Dopamine (DA) is responsive to hormonal manipulations and has been implicated in
      the regulation of female rat sexual behavior. In the present studies,
      extracellular DA levels were assessed in the medial preoptic area (MPOA) of
      ovariectomized female rats in response to exogenous ovarian hormones and during
      sexual activity. In female rats primed with a low dose of estradiol benzoate (2
      microg), but not with a higher dose (20 microg), a 500-microg progesterone
      injection increased extracellular DA and facilitated copulatory behavior.
      Extracellular DA levels in the MPOA were further augmented during sexual
      interactions with a male rat in a nonpacing copulatory chamber by either perineal
      or vaginal stimulation. However, in a pacing chamber, DA efflux did not increase,
      although the metabolites rose significantly during copulation. Together, these
      findings suggest that extracellular DA in the MPOA responds to the hormonal state
      of the female rat and may contribute to her expression of sexual behavior.

PMID- 10959537
TI  - Milk delivery schedules and stomach preloading alter patterns of suckling
      behavior by newborn rats on a surrogate nipple.
AB  - Newborn rat pups tested before suckling experience attached to and ingested milk
      from the surrogate nipple. Time attached to the nipple and amount of milk
      ingested depended on the schedule of milk infusion through the nipple. More
      frequent milk infusions resulted in more frequent disengagements from the nipple
      during the test, less time attached to the nipple, and less body weight gain. The
      initial patterns of attachment behavior--continuous or intermittent--were
      reproduced later when rats were tested on the surrogate nipple. Preloading of the
      stomach with milk effectively altered both attachment and ingestion from the
      nipple, whereas preloading with the same amount of water had no effect on
      suckling behavior. The data suggest that newborn rats flexibly adjust their
      attachment behavior to peculiarities of milk delivery through the surrogate
      nipple and reproduce the initial attachment pattern when reexposed to the
      surrogate nipple.

PMID- 10959538
TI  - Endogenous opioid facilitation of maternal memory in rats.
AB  - In rats, contact with pups at parturition establishes a form of maternal memory
      that enables female rats to respond rapidly to pups in the future. Treatment of
      pregnant female rats with the long-lasting micro opioid receptor antagonist, beta
      funaltrexamine (beta-FNA), prior to parturition interfered with the establishment
      of maternal memory. Similar treatment 3 hr postpartum resulted in disrupted
      retention of maternal memory that appeared nonspecific, with both drug- and
      vehicle-treated rats displaying a deficit. However, infusion of the opioid
      antagonist 24 hr postpartum had no effect on the retention of maternal memory
      tested 7 days later. These findings indicate that the establishment of maternal
      memory is mediated by endogenous opioid activity around the time of parturition.

PMID- 10959539
TI  - Ultrasonic vocalizations by rat pups after adrenergic manipulations of brown fat
      metabolism.
AB  - Rat pups emit ultrasonic vocalizations (USVs) during cold challenge. R. F. Kirby
      and M. S. Blumberg (1998) suggested that when brown adipose tissue (BAT)
      thermogenesis fails to compensate for body heat loss and heart rate declines,
      infant pups maintain venous return to the heart with a mechanical maneuver that
      is accompanied by ultrasonic emissions. Thus, manipulations that attenuate or
      enhance BAT thermogenesis should have inverse effects on cold-induced USVs. The
      authors found that hexamethonium (10 mg/kg) and propranolol (1 and 20 mg/kg)
      attenuated BAT metabolism while enhancing USV production, and norepinephrine (NE,
      800 microg/kg) enhanced BAT metabolism while ultrasonic emissions decreased. The
      findings are consistent with the hypothesis that BAT metabolism influences USVs
      during cold challenge by affecting cardiac rate and inducing compensatory,
      homeostatic responses.

PMID- 10959540
TI  - Does intranasal application of zinc sulfate produce anosmia in the rat?
AB  - Transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from
      olfactory sensory neurons to the olfactory bulb as well as odor detection and
      discrimination were examined in rats in which each nasal epithelium had been
      irrigated with 0.1-0.5 ml 5% zinc sulfate. After treatment, rats showed few or no
      deficits in discriminating among odors and in detecting high (1%-0.01%)
      concentrations of ethyl acetate, but some had deficits in detecting lower
      concentrations of the odor. In most cases, HRP reaction product filled more than
      30% of olfactory bulb glomeruli 2-4 days after treatment with ZnSO4. The
      behavioral outcomes are in agreement with recent reports of considerable savings
      in olfaction even after severe reduction of afferent projections to the olfactory
      bulb. We conclude that, in the rat, intranasal application of ZnSO4, as generally
      practiced, does not produce anosmia.

PMID- 10959541
TI  - Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in
      humans.
AB  - Little is known about the acute effects of psychoactive drugs on impulsivity and
      decision making in humans. This study examined the effects of d-amphetamine (AMP;
      10 and 20 mg; N = 20) and ethanol (EtOH; 0.2, 0.4, and 0.8 g/kg; N = 17) on the
      stop task, a putative measure of behavioral inhibition and impulsivity in healthy
      human volunteers. The stop task provides a measure of the reaction time (RT)
      needed to inhibit a response (Stop RT [SRT]), relative to the time taken to
      execute a simple response (Go RT [GRT]). Healthy volunteers performed the stop
      task before and after receiving one of the drugs. AMP decreased SRT-that is,
      improved inhibition-only in participants with slow baseline SRTs. EtOH increased
      SRTs-that is, impaired inhibition-at doses that did not affect GRTs. These
      results suggest that AMP and EtOH have specific and distinctive effects on the
      ability to inhibit responses. Impairment in the ability to inhibit responses is
      thought to reflect a certain form of impulsivity.

PMID- 10959542
TI  - Effects of d-amphetamine and alcohol on a measure of behavioral inhibition in
      rats.
AB  - This study was designed to develop a version of the stop task, a putative measure
      of behavioral inhibition, for use in rats and to assess the effects of d
      amphetamine (AMP) and alcohol (ALC). The stop task provides a quantitative index
      of the ability to inhibit a response that has been initiated. Rats (N = 11) were
      tested after intraperitoneal injections of AMP (0.125, 0.25, 0.5, 1.0 mg/kg) and
      ALC (250, 500, 750 mg/kg). AMP improved the ability to inhibit responses only in
      rats with relatively poor inhibitory performance at baseline. ALC impaired
      inhibition at doses that did not affect simple reaction time. The results support
      the sensitivity, reliability, and validity of the procedure as a measure of
      behavioral inhibition in rats and are highly concordant with a parallel study
      conducted with humans.

PMID- 10959543
TI  - Effect of excitatory amino acid, dopamine, and oxytocin receptor antagonists on
      noncontact penile erections and paraventricular nitric oxide production in male
      rats.
AB  - In male rats, noncontact erections occur concomitantly with an increase in NO2-
      and NO3- in the paraventricular nucleus of the hypothalamus (PVN). In the present
      study, both responses were reduced by the blockade of PVN excitatory amino acid
      receptors by dizocilpine, (+)-MK-801(1 and 5 microg), but not by 6-cyano-7-nitro
      quinoxaline-2,3-dione (5 microg) or (+)-2-amino-4-phosphono-butanoic acid (5
      microg). Also ineffective when injected into the PVN were the dopamine
      antagonists SCH 23390 (5 microg), S(+)-raclopride (10 microg), and cis
      flupenthixol (10 microg), and the oxytocin antagonist d(CH2)5Tyr(Me)2-Om8
      vasotocin (1 microg). However, when the last was given into the lateral
      ventricles, it reduced noncontact erections without modifying NO2- and NO3-
      increases. These results suggest that excitatory amino acid transmission
      increases in the PVN during noncontact erections. This may contribute to
      increased NO production in the PVN, and it may activate oxytocin neurons
      mediating this sexual response.

PMID- 10959544
TI  - Nasal tumors in rats following long-term inhalation exposure to 1,4
      dichlorobutene-2 (DCB).
AB  - This study was conducted to elucidate the time- and dose-response relationships
      of long-term, low-level 1,4-dichlorobutene-2 (DCB) inhalation exposure to nasal
      tumor induction in rats. Male Crl:CD BR rats were exposed 6 hours per day, 5 days
      week to 0, 0.1, 0.3, or 1.0 ppm DCB for up to 19 months; some rats were
      sacrificed at various time intervals during the study. After 19 months of
      exposure, surviving rats were held without treatment for an additional 5 months.
      Tissues from the respiratory tract, lymph nodes, and brain were evaluated
      microscopically. Compound-related non-neoplastic lesions were observed in the
      nasal cavities of rats in the 1.0 ppm group after three months of exposure and in
      the other two groups after twelve months of exposure. The lesions were
      progressive in severity and frequency. A statistically significant increase in
      benign nasal tumors (adenomas) occurred in rats from all three DCB-exposed
      groups. The adenomas occurred in the respiratory region of the nasal cavity and
      were first observed in the 1.0 ppm group at study month 10. Malignant nasal
      tumors occurred in the olfactory region of the nasal cavity and were
      statistically increased at 1.0 ppm.

PMID- 10959545
TI  - Impact of antenatal exposure of mice to fenfluramine on cardiac development and
      long-term growth of the offspring.
AB  - The objective of this investigation was to determine, in a placebo-controlled
      manner, whether antenatal exposure to formulations of fenfluramine and
      dexfenfluramine impacted cardiac development and long-term growth of exposed mice
      offspring. One hundred forty-four CD-1 mice were randomized to six treatment
      groups (n=23 or 25) to obtain, per group, 5 gravids for killing on gestational
      day (GD) 15 and < or =10 deliveries for assessing growth of the offspring. Either
      fenfluramine preparation was administered in feed bars in two doses: 1 and 3.2
      times the equivalent human daily dosage according to body surface area. The drugs
      were given from 2 weeks before mating until GD 15. The mice ingested each drug at
      target values, averaging 10.5+/-0.3 and 31.8+/-1.9 mg/kg/d for fenfluramine and
      5.0+/-0.2 and 16.2+/-0.4 mg/kg/d for dexfenfluramine. The drug concentration was
      about 36% in the fetal brain compared with the adult brain. The maternal and the
      offspring hearts, including mitral and aortic valves, of fenfluramine-exposed
      mice were indistinguishable from the placebo-exposed mice. The duration of
      gestation and the litter size were the same between the treatment groups. The
      mean body weights, body lengths, and head circumferences and early functional
      testing did not differ significantly between the fenfluramine or dexfenfluramine
      exposed offspring and the placebo-exposed offspring. There were no significant
      treatment differences in growth measured as body weights to PND 120. Neither
      fenfluramine formulation, given before conception and during gestation, impacted
      cardiac development and long-term growth of the mice offspring.

PMID- 10959546
TI  - Glycidol modulation of the immune responses in female B6C3F1 mice.
AB  - The immunotoxic potential of glycidol was evaluated in female B6C3F1 mice using a
      battery of functional assays and three host resistance models. Glycidol was
      administered to the animals by oral gavage as a solution in sterile distilled
      water daily for 14 days at doses of 25, 125 and 250 mg/kg. In tier I, we observed
      that glycidol exposure produced a dose-related decrease in splenocyte IgM
      antibody-forming cell response to sheep red blood cells (sRBC); the spleen
      natural killer (NK) cell activity was also decreased. A decrease in B cell
      proliferative responses to anti-IgM F(ab')2 and/or interleukin-4 (IL-4) was
      observed while the splenocyte proliferative responses to T cell mitogen ConA and
      B cell mitogen LPS were not affected. The splenocyte proliferative response to
      allogeneic cells as evaluated in the mixed leukocyte reaction (MLR) to DBA/2
      spleen cells was not affected. In tier II, we found that exposure to glycidol
      decreased the number and percentage of B cells and the absolute number of CD4+ T
      cells in the spleen while the number of total T cells, CD8+ T cells and CD4+CD8+
      T cells was not affected. The cytotoxic T lymphocyte (CTL) response to mitomycin
      C-treated P815 mastocytoma was not affected; the cytotoxic activity of peritoneal
      macrophages was not suppressed. Moreover, the host resistance to Listeria
      monocytogenes was not affected although a slight increase in host resistance to
      Streptococcus pneumoniae was observed. However, exposure to glycidol decreased
      host resistance to the B16F10 melanoma tumor model with the maximal tumor
      formation in lung observed in the high dose group. Overall, these dada support
      the finding that glycidol is an immunosuppressive agent in female B6C3F1 mice.

PMID- 10959547
TI  - Effect of intra-tracheal instillation and inhalation of silicon dioxide on some
      biochemical variables in broncho-alveolar lavage fluid and lung histopathology in
      rats.
AB  - In the present study, the bronchial alveolar lavage fluid (BALF) biochemical and
      lung histopathological changes occurring in response to single large intra
      tracheal exposure to silica have been compared to the changes seen after
      continued chronic exposure via inhalation. Male albino rats (200-250gms) were
      exposed to silicon dioxide via intratracheal instillation (8mg/0.05ml saline) and
      whole body inhalation (200mg/m3, 6 hours/day for 2 and 4 weeks) in separate
      groups . The respective control animals were instilled with normal saline
      (0.05ml) or exposed to fresh air in simulation chamber for the same duration.
      BALF was analyzed for total protein, elastase, malondialdehyde (MDA) levels and
      catalase activity and histopathology of right lung was carried out after 4 weeks
      post-exposure in intra-tracheal model and after 2 and 4 weeks of exposure in the
      inhalation model. The levels of total protein, elastase and malondialdehyde (MDA)
      were significantly elevated, while catalase activity was significantly decreased
      in the BALF of exposed animals as compared to controls. The histopathological
      studies of lungs, showed exudates of inflammatory cells, chiefly of macrophages
      in the alveolar spaces and interstitial septa with multifocal nodular
      granulomatous lesions. The biochemical findings in BALF of both the models
      indicate inflammatory changes, lipid peroxidation and fibrosis. However,
      comparatively lower catalase activity and higher elastase levels in the 4 week
      inhalationally exposed group than the 4 week post intratracheally exposed group,
      suggests that these parameters may be affected by acute and chronic exposure and
      require further confirmation.

PMID- 10959548
TI  - In vitro inhibition of carcinogen-induced mutagenicity by Cassia occidentalis and
      Emblica officinalis.
AB  - Aqueous extracts of Cassia occidentalis Linn. (Leguminoceae) and Emblica
      officinalis Gaertn. (Euphorbiaceae) were screened for effectiveness in inhibiting
      mutagenicity of aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P) in the Ames test.
      Antimutagenicity was evaluated using Salmonella typhimurium strains TA 98 and TA
      100. In the assay, metabolic activation of AFB1 (0.5 microg/plate) and B[a]P (1
      microg/plate) was mediated by rat liver S9 preparation. Although both plants
      inhibited mutagenicity, E. officinalis had more inhibitory effect than C.
      occidentalis. Their action is possibly mediated through interactions with
      microsomal activating enzymes. Their inhibitory action on chromosomal aberrations
      together with present results suggest that these plants have potent antimutagenic
      and anticarcinogenic activities against mutagens requiring metabolic activation.

PMID- 10959549
TI  - Peripheral neuropathy in B6C3F1 mice and SD rats induced by chronic intermittent
      insulin hypoglycemia.
AB  - The effects of sustained insulin-induced hypoglycemia on peripheral nerves were
      examined in 9-10-week old female B6C3F1 mice and 9-10-week old female SD rats.
      Insulin was administered via osmotic minipumps at a dose of 81 IU/kg/day for 2
      consecutive weeks. Mice and rats treated with this high insulin dose showed
      marked hypoglycemia, resulting in half the normal blood glucose level,
      hypothermia, impaired motor nerve conduction velocity, and an increased incidence
      of peripheral nerve lesions, consisting of nerve fiber degeneration characterized
      by irregular myelin sheaths and axonal atrophy.

PMID- 10959550
TI  - Acid and alkaline phosphatase activities in a novel phosphorothionate (RPR-11)
      treated male and female rats. Evidence of dose and time-dependent response.
AB  - The effect of a novel phosphorothionate, the methyl ester of 2-butenoic acid-3
      diethoxy phosphinothioyl (RPR-II) was studied on membrane bound target enzymes
      Acid (AcP) and Alkaline (AkP) Phosphatases in different tissues of male and
      female albino Wistar rats. Three sub-chronic doses 0.014 (low), 0.028 (medium)
      and 0.042 (high)mg/kg-1 were administered to the rats daily for a period of 90
      days. The long term and repeated administration of RPR-II caused significant
      increase of AcP and AkP in serum and kidney (AcP), whereas these enzymes
      simultaneously decreased significantly in liver, kidney (female rat AkP) and lung
      tissues in both male and female rats after 45 and 90 days of treatment. However,
      the kidney AcP increased significantly in both the sexes which is suggestive of
      an increase in synthesis of this enzyme which may be an adaptive mechanism to the
      toxicant stress. The changes in serum, liver, kidney and lung of both male and
      female rats by this compound were statistically significant when compared with
      two way Anova showing that they are dose and time dependent. The alterations in
      male rats were statistically insignificant when compared with female rats showing
      no sexual dimorphism by this compound. Recovery was observed after 28 days of
      post treatment (withdrawal study) indicating reversal of the toxic symptoms once
      the toxicant is removed. High degree negative correlation was observed for serum
      versus liver and lung and in other cases substantial correlation was observed.
      The changes observed in these enzymes showed that liver was most susceptible
      followed by lung and kidney. There are marker enzymes and their increase in
      different tissues might be due to the increased permeability of plasma membrane
      or cellular necrosis, showing the stress condition of the treated rats. This
      investigation elucidates the effect of these biomarker enzymes which increased in
      blood, might be due to the necrosis of liver, kidney and lung tissues by this
      compound.

PMID- 10959551
TI  - An investigation into the effect and mechanisms of action of nicotine in
      inflammatory bowel disease.
AB  - OBJECTIVE AND DESIGN: To determine the effect of nicotine on colonic inflammation
      in the trinitrobenzenesulphonic acid (TNBS) model of inflammatory bowel disease
      in comparison with sulphasalazine. MATERIALS: Male Wistar rats were used for the
      in-vivo and ex-vivo studies. In-vitro studies were performed using human leukemia
      peripheral blood monocyte cells (THP-1 cells) grown in continuous culture.
      TREATMENT: Rats were given access to either nicotine (5 or 100 microg/mL) or
      sulphasalazine (375 microg/mL) in their drinking water for 10 or 2 days
      respectively before and 3 days after TNBS administration. THP-1 cells were
      treated with nicotine (10(-14) to 10(-11) M) for 2 h before and after stimulation
      with 3 microg/mL lipopolysaccharide (LPS). METHODS: Inflammation in the TNBS
      model was assessed by measuring the tissue myeloperoxidase activity, leukotriene
      B4 concentration, inducible nitric oxide protein expression, the ex-vivo
      production of tumour necrosis factor alpha (TNFalpha), macroscopic damage score,
      plasma corticosterone levels and by a qualitative histological evolution. The
      effect of nicotine on TNFalpha production in LPS stimulated THP-1 monocyte cells
      in-vitro was also determined. Statistical comparisons were made using the Mann
      Whitney U-test for the macroscopic damage score and an ANOVA for all other
      parameters. RESULTS: TNBS treated rats given access to 100 microg/mL nicotine in
      their drinking water had a marked reduction in several of the markers of
      inflammation compared to control TNBS treated rats, but a greater reduction was
      found at 5 microg/mL nicotine or 375 microg/mL sulphasalazine, the latter
      producing comparable reductions in inflammation to the low dose nicotine.
      Nicotine also caused a significant reduction in TNFalpha release from THP-1
      cells. CONCLUSIONS: Nicotine reduced inflammation in the TNBS model of colonic
      damage confirming the use of nicotine in IBD although the choice of dose requires
      further investigation. The mechanism of action of nicotine does not involve
      increased corticosterone levels, but may be a consequence of a reduction in
      TNFalpha or leukotriene B4 production.

PMID- 10959552
TI  - Expression of hepatocyte growth factor and c-met in ulcerative colitis.
AB  - OBJECTIVE AND DESIGN: This study was designed to determine if the hepatocyte
      growth factor (HGF)-Met system is involved in the repair process of inflamed
      mucosa of ulcerative colitis (UC) and in the development of UC-associated
      colorectal cancer. MATERIALS AND METHODS: HGF and c-met gene expressions were
      quantified in colonic mucosal specimens from healthy control subjects, patients
      with UC and patients with UC-associated colorectal cancer, using the competitive
      reverse transcription-polymerase chain reaction. Expression of HGF protein was
      determined by immunoblot analysis. Expression of c-Met protein was analyzed
      immunohistochemically. RESULTS: HGF and c-met gene expressions were increased in
      inflamed mucosa of UC, compared with control subjects. Gene expression of HGF was
      also increased in the surrounding inflamed mucosa of UC-associated cancers. In
      cases in which the HGF gene expression was increased, an apparent increase in
      protein levels of HGF in inflamed mucosa of UC were observed by immunoblot
      analysis. The c-met gene was overexpressed in UC-associated cancers and a high
      level of immunoreactivity of the c-Met protein was immunohistochemically detected
      within the cancer cells. CONCLUSION: We showed that HGF and c-met expression is
      increased in the inflamed mucosa of UC and that c-met is overexpressed in UC
      associated colorectal cancers. These observations suggest HGF-Met system is
      involved in the repair process of the inflamed mucosa of UC and provide further
      support for the view that the inappropriate expressions of both HGF and c-met
      genes predispose to the development of colorectal cancer in patients with UC.

PMID- 10959553
TI  - Spontaneous leukocyte rolling in rat and mouse microvessels is independent of
      mast cell activity.
AB  - OBJECTIVE AND DESIGN: The role of mast cells in spontaneous leukocyte rolling in
      venules of the mouse cremaster muscle and rat mesentery was investigated.
      MATERIALS: The experiments were carried out using mast cell-deficient rats
      (Ws/Ws), WBB6F1 mice (W/Wv), and their congenic littermates (wild type).
      TREATMENT: Administration of compound 48/80 intraperitoneally (50 microg) in rats
      and intrascrotally (5 microg) in mice, 4 h prior to the experiments. METHODS:
      Intravital microscopy of the terminal vascular beds in mouse cremaster muscle and
      rat mesentery. RESULTS: The level of spontaneous leukocyte rolling and the
      rolling velocity in venules of mast cell-deficient animals exactly matched that
      seen in wild-type animals. Challenge with compound 48/80 markedly increased
      leukocyte adhesion and emigration in venules of wild-type animals. In contrast,
      the number of adherent and extravascular leukocytes was very low in compound
      48/80-challenged animals lacking mast cells and did not differ from that seen in
      control animals treated with phosphate-buffered saline. CONCLUSIONS: The presence
      or activation of mast cells has no bearing on spontaneous leukocyte rolling, at
      least not in rat and mouse microvessels.

PMID- 10959554
TI  - Synergistic antiinflammatory effect of NF-kappaB inhibitors and steroidal or non
      steroidal antiinflammatory drugs in the pleural inflammation induced by
      carrageenan in mice.
AB  - OBJECTIVES: Experiments were designed to determine whether or not inhibitors of
      NF-Kappa B (NF-kappaB) exhibit antiinflammatory effects when assessed in
      carrageenan-induced pleural inflammation in the mouse. MATERIAL AND METHODS:
      Adult mice of both sexes received pyrrolidine dithiocarbamate (PDTC) or
      sulfasalazine administered intraperitoneal by at several time points before
      intrapleural injection of carrageenan (1%) and the exudation and the total and
      differential cells were analysed. RESULTS: PDTC or sulfasalazine largely and
      almost completely inhibited the leukocyte infiltration and the exudation induced
      by intrapleural administration of carrageenan, when assessed 4 h (but not 48 h)
      after carrageenan injection. The combination of subliminal doses of PDTC or
      sulfasalazine with steroidal (dexamethasone) or non-steroidal (indomethacin,
      meloxicam, nabumetone, diacerein) antiinflammatory drugs, which alone had no
      antinflammatory action, greatly inhibited both the pleural cell infiltration and
      exudation induced by carrageenan. The highest inhibition of leukocyte
      infiltration was observed with the combination of PDTC or sulfasalazine with
      dexamethesone (84 and 75%, respectively). CONCLUSIONS: These results indicate
      that nuclear factor-kappaB might play an important role in the modulation of the
      early phase of the pleural inflammatory response induced by carrageenan in the
      mouse. Furthermore, our results demonstrate for the first time a marked
      synergistic interaction among dexamethasone--and to a lesser extent among
      nonsteroidal antiinflammatory drugs--and the NF-kappaB inhibitors, suggesting
      that this association may be of potential interest for the management of certain
      inflammatory processes, including asthma therapy.

PMID- 10959555
TI  - Regulation of LFA-3 (CD58) by dexamethasone and retinoic acids in vitro.
AB  - INTRODUCTION: The oral form of lichen planus (OLP) is a chronic inflammatory
      disease characterized by the accumulation of T cells below the basal layer of the
      buccal mucosa. We have previously shown that the adhesion molecule lymphocyte
      function-associated antigen-3 (LFA-3; CD58) is up-regulated in lesional tissue
      and may play an important part in the molecular pathology of this disease. OLP is
      often treated with glucocorticoids, and glucocorticoid-resistant cases with
      retinoid drugs. However, it is not yet known whether the pharmacological action
      of these drugs is mediated directly or indirectly via LFA-3. METHODS: In the
      present experiments we have used the technique of flow cytometry (FCM) to
      accurately measure the effects of the glucocorticoid dexamethasone (DEX), all
      trans retinoic acid (ATRA) and 13-cis retinoic acid (13RA) on LFA-3 expression by
      three main cell types found in OLP lesions--an oral epithelial cell line (KB
      cells), a T lymphocyte cell line (Jurkat cells) and an antigen presenting
      myelomonocytic cell line (U937 cells). The relative levels of the specific
      receptors for the drugs were also determined in these cell lines using FCM.
      RESULTS: ATRA and 13RA were found to have a more pronounced inhibitory effect on
      LFA-3 expression than did DEX, the U937 cells being the most sensitive and the KB
      cells the least affected. The KB cells also expressed the lowest relative levels
      of drug receptors. DISCUSSION: The results showed that the three drugs
      differentially down-regulated LFA-3 expression by each of the cell lines.
      Moreover, the relative inhibitory effects of the drugs appeared to be related to
      the relative expression of the specific drug receptors by each of the cells. Our
      findings suggest that the down-regulation of LFA-3 in vitro might explain at
      least partly the efficacy of glucocorticoids and retinoids in the treatment of
      inflammatory diseases in vivo.

PMID- 10959556
TI  - Upregulation of cyclooxygenase-1 and the PGE2 receptor EP2 in rat and human
      mesangioproliferative glomerulonephritis.
AB  - OBJECTIVE AND DESIGN: Glomerular expression and localization of the two
      cyclooxygenase isoforms, Cox-1 and Cox-2, and the prostaglandin E2 receptor EP2
      were investigated in a rat model of transient mesangioproliferative
      glomerulonephritis. Cox expression was also studied in biopsies from patients
      with IgA nephropathy. MATERIALS AND TREATMENT: After induction of
      glomerulonephritis by i.v. injection of a monoclonal anti-Thy1.1 antibody, rats
      were sacrificed at day 2, 6, 12 and 56. Changes in protein expression were
      detected by immunohistochemistry. Glomerular mRNA levels were analyzed by real
      time polymerase chain reaction (PCR). RESULTS: In normal rat kidney,
      immunoreactivity of Cox-1 was detected predominantly in collecting duct cells and
      that of Cox-2 in the macula densa. Cox-1 staining showed a massive transient
      increase in diseased glomeruli at day 6, localized mainly to mesangial cells
      coinciding with cell proliferation, which also peaked at day 6. Upregulation of
      Cox-1 was also evident at the mRNA level (4 fold). Cox-2 expression in the macula
      densa region transiently increased at day 6, but no significant upregulation of
      Cox-2 was observed in glomerular cells at any time point. Prostaglandin E2
      receptor EP2 mRNA and protein were detected in rat glomeruli. EP2
      immunoreactivity was prominent on podocytes in normal rats while at day 6 of the
      disease also mesangial cells stained positive. In biopsies of patients with IgA
      nephritis, predominant expression of Cox-1, but not Cox-2, was found in
      glomeruli, whereas Cox-2 was strongly expressed in infiltrating interstitial
      cells. CONCLUSIONS: The upregulation of glomerular Cox-1 but not Cox-2 and the
      parallel induction of the EP-2 receptor, which was shown to mediate cAMP
      accumulation in mesangial cells, suggest that induction of prostaglandin
      formation may contribute to the resolution rather than to the progression of anti
      Thy1.1 nephritis. The expression pattern of Cox-1 and Cox-2 in human IgA
      nephritis points to a role for both Cox isoforms in human glomerular
      inflammation.

PMID- 10959557
TI  - In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from
      dispersed canine skin mast cells and the human mast cell line HMC-1.
AB  - OBJECTIVE AND DESIGN: To examine the inhibitory potential of rupatadine, a new H1
      antihistamine and anti-PAF agent, on histamine and TNF-alpha release. Comparison
      with an H1-antihistamine (loratadine) and a PAF-antagonist (SR-27417A). MATERIAL:
      Dispersed canine skin mast cells were used to assess the effect of the drugs
      tested on FcepsilonRI-dependent and -independent histamine release; the human HMC
      1 cell line was used to study TNF-alpha release. TREATMENT AND METHODS: Before
      stimulation mast cell populations were treated with increasing concentrations of
      rupatadine, loratadine and SR-27417A. Histamine and TNF-alpha release were
      measured following 15-30 min and 3 h activation, respectively. RESULTS: The IC50
      for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release
      was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas
      for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM.
      SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A
      inhibited TNF-alpha release with IC50 2.0+/-0.9 microM, 2.1+/-1.1 M and 4.3+/-0.6
      microM, respectively. CONCLUSIONS: Rupatadine and loratadine showed similar
      inhibitory effect on histamine and TNF-alpha release, whereas SR-27417A only
      exhibited inhibitory effect against TNF-alpha.

PMID- 10959558
TI  - Effects of meloxicam on oxygen radical generation in rat gastric mucosa.
AB  - AIM AND DESIGN: In addition to a deficiency of endogenous prostaglandins due to
      inhibition of cyclo-oxygenase and a host of prostaglandin-mediated effects on
      mucosal protection, it has recently been proposed that neutrophil- and oxygen
      radical - dependent microvascular injuries may be important prime events that
      lead to mucosal injury induced by non-steroidal anti-inflammatory drugs.
      Therefore, we evaluated the role of oxygen free radicals in the pathogenesis of
      acute gastric ulceration induced by meloxicam, a preferential COX-2 inhibitor.
      MATERIAL: Studies were performed in Wistar rats. TREATMENT: Meloxicam was given
      by oral administration (3.75-30 mg/kg body weight). METHODS: Determinations were
      made of gastric mucosal injury, xanthine-oxidase, myeloperoxidase and superoxide
      dismutase activities, as well as the effect of meloxicam on gastric prostaglandin
      synthesis (PGE2 levels) and glutathione homeostasis. RESULTS: Oral administration
      of meloxicam dose-dependently (3.75-30 mg/kg) caused acute gastric haemorrhage
      erosions. The total area of gastric lesions increased with time until 24 hours
      after dosing. Xanthine-oxidase activity increased significantly after
      administration of the drug. Myeloperoxidase activity, as an index of neutrophil
      infiltration, as well as glutathione peroxidase, an important enzyme that
      scavenges lipid peroxides, were unaffected by meloxicam administration. In
      addition, superoxide dismutase activity, PGE2 and glutathione levels were
      significantly reduced. CONCLUSION: These results support the hypothesis that in
      addition to suppression of prostaglandin synthesis, oxygen free radicals,
      probably derived via the action of xanthine oxidase, the decrease in superoxide
      dismutase activity, and the depletion of mucosal glutathione contribute to the
      pathogenesis of meloxicam-induced ulceration.

PMID- 10959559
TI  - Halotolerance of the yeast Arxula adeninivorans LS3.
AB  - The non-pathogenic, dimorphic, ascomycetous yeast Arxula adeninivorans LS3 is
      halotolerant. It can grow in a minimal medium containing up to 20% NaCl. The
      growth parameters are only weakly influenced by 10% NaCl. However, NaCl in a
      concentration higher than 10% causes a decrease in the specific growth rate, a
      longer adaptation phase and a lower cell count in the stationary growth phase.
      Concentrations of glycerol and trehalose, which differed 100-fold in magnitude in
      a salt free medium, are also influenced differently by salt. NaCl induces
      accumulation of intracellular glycerol in exponentially growing cells but a
      reduced concentration of intracellular trehalose in stationary cells. Transcripts
      of the genes ARFC3, encoding a component of the replication factor C, and GAA,
      encoding a secretory glucoamylase, can be detected only in cells cultured in
      media with NaCl concentrations below 10%. Furthermore, NaCl in high concentration
      reduces the level of secreted proteins including glucoamylase end invertase.

PMID- 10959560
TI  - Phylogenetic position and physiology of Cerinosterus cyanescens.
AB  - Partial 25S rRNA sequencing of Cerinosterus cyanescens showed it to be a close
      relative of Microstroma juglandis, a member of the basidiomycetous order
      Microstromatales. It is unrelated to the generic type species, C. luteoalba,
      which is a member of the order Dacrymycetales. The clinical occurrence of C.
      cyanescens is possibly explained by its thermotolerance and lipolytic activity.
      The species' nutritional profile is established. Growth on n-hexadecane is rapid;
      it grows well on typical plant constituents like gallic, tannic, vanillic, quinic
      and p-coumaric acids, but not on 3-hydroxybenzoic acid, phenol and hydroquinone.
      The failure to assimilate D-galactose, L-sorbose and ethylamine, the presence of
      urease and sensitivity to cycloheximide are diagnostic for the species.

PMID- 10959561
TI  - Thiosulfate reduction and alanine production in glucose fermentation by members
      of the genus Coprothermobacter.
AB  - Coprothermobacter platensis is an anaerobic, proteolytic, thermophilic bacterium,
      which is phylogenetically related to the genera Fervidobacterium and Thermotoga.
      The organism was found to reduce thiosulfate to sulfide during growth on
      carbohydrates and proteinaceous substrates. Growth on glucose was inhibited by
      hydrogen, but this inhibition was overcome by thiosulfate reduction, stirring,
      increasing the headspace volume and coculturing with a hydrogen-consuming
      methanogen. Alanine was detected during glucose fermentation, its formation was
      influenced by the hydrogen concentration in the gas phase suggesting an electron
      sink mechanism, as was previously reported for the phylogenetically related
      Thermotogales and the archaeal hyperthermophile Pyrococcus furiosus.

PMID- 10959562
TI  - Changes of cell size distribution during the batch culture of Arthrobacter strain
      PI/1-95.
AB  - The size distributions of an arthrobacter, approximately 1 microm in diameter,
      were analysed using a Coulter Multisizer II instrument thereby making it possible
      to distinguish between the different stages in the morphological cycle. The
      results indicated that at the beginning of exponential phase a shift occurred
      from large to smaller cells, the cell size distributions in both categories were
      asymmetric, skewed towards higher values than the means. During the course of the
      batch culture the cells in the larger class decreased in size and the two classes
      coalesced. The size distribution of the smaller class exhibited an additional
      shift towards smaller cells. After which neither the number of classes nor the
      size distribution changed. It was concluded that the Coulter Multisizer II
      instrument provides a feasible method to extract information not only about mean
      cell size but also about cell size distributions.

PMID- 10959563
TI  - Biosystematic studies on novel streptomycetes from soil.
AB  - Members of three putatively novel Streptomyces species, designated Streptomyces
      groups A, B and C, were repeatedly isolated from environmental samples taken from
      four hay meadow plots at Cockle Park Experimental Farm, Northumberland (UK).
      Representative isolates were found to have properties consistent with their
      classification in the genus Streptomyces and were recovered in three taxa using
      different phenotypic criteria, namely morphological and pigmentation properties,
      rapid enzyme tests, and whole-organism fatty acid, protein electrophoretic and
      pyrolysis mass-spectrometric data. The isolates were rapidly characterised as
      three taxonomic groups using pyrolysis mass spectrometry. The three taxa were
      also distinguished from one another and from validly described species of
      Streptomyces using rapid enzyme tests based on the fluorophores 7-amino
      methylcoumarin and 4-methylumbelliferone, and computer-assisted identification
      procedures. The results indicate that selective isolation and rapid
      characterisation of streptomycetes using pyrolysis mass spectrometry provide a
      practical way of determining the phenotypic species diversity of streptomycetes
      in natural habitats. The experimental data also indicate that representative
      sampling of cultivable streptomycetes from soil can best be achieved using a
      multi-step extraction procedure coupled with the use of selective isolation
      procedures.

PMID- 10959564
TI  - The basidiomycetous yeast Rhodotorula yarrowii comb. nov.
AB  - Sequence analysis of the D1/D2 domains of the large subunit rDNA of Cryptococcus
      yarrowii (CBS 7417) indicates that this species does not belong to the
      hymenomycetous fungi, but instead is of urediniomycetous affinity. Therefore, the
      name change Rhodotorula yarrowii comb. nov. is proposed. The cell wall of the
      species contains xylose, a character considered by most authors to indicate fungi
      of hymenomycetous affinity. However, our results show that xylose may occur in
      minor amounts in the cell walls of urediniomycetous fungi. A high mannose content
      of the cell walls may be a more reliable character for urediniomycetous yeasts.

PMID- 10959565
TI  - Rapid characterisation of deep-sea actinomycetes for biotechnology screening
      programmes.
AB  - A continual need in natural product discovery is dereplication, that is the
      ability to exclude previously tested microorganisms from screening programmes.
      Whole-cell fingerprinting techniques offer an ideal solution to this problem
      because of their rapidity and reproducibility, dependence on small samples, and
      automation. One such technique, Curie-point pyrolysis mass spectrometry (PyMS),
      has been deployed for the characterisation of a unique collection of
      actinomycetes recovered from Pacific Ocean sediments approximately 2000 to 6500 m
      below sea level. This paper addresses the question: to what extent are
      pyrogroups, defined on the basis of PyMS fingerprinting, related to
      classifications derived from more conventional microbial systematics? A
      collection of 44 randomly chosen deep-sea rhodococci were coded and subjected to
      a double-blind PyMS and numerical taxonomic (NT) analysis; the latter sorted the
      strains into clusters (taxospecies) using large sets of equally weighted
      phenotypic data. At the end of the experiment the codes were disclosed and the NT
      classification shown to generate 6 homogeneous clusters corresponding to
      different deep-sea sites. The matching of these clusters with the resulting
      pyrogroups was very high with an overall congruence of nearly 98%. Thus, PyMS
      characterisation is directly ascribable to the phenotypic variation being sought
      for biotechnology screens. Moreover, the exquisite discriminatory power of PyMS
      readily revealed infraspecific diversity in these industrially important
      bacteria.

PMID- 10959566
TI  - Taxonomic and phylogenetic analysis of Saprolegniaceae (Oomycetes) inferred from
      LSU rDNA and ITS sequence comparisons.
AB  - The aim of this study was to improve our knowledge about the taxonomy and
      phylogeny of the family Saprolegniaceae, a group of water molds including several
      pathogens of plants, fish and crustacea. ITS and LSU rDNA were sequenced for
      representatives of forty species corresponding to ten genera (Achlya,
      Aphanomyces, Brevilegnia, Dictyuchus, Leptolegenia, Plectospira, Pythiopsis,
      Saprolegnia, Thraustotheca). Phenetic and cladistic analyses were then carried
      out. The species Brevilegnia bispora does not appear to belong to the family
      Saprolegniaceae. Plectospira myrianda clusters with Aphanomyces spp. and they
      constitute an ancestral group. (Thraustotheca clavata is closely related to the
      eccentric species of the genus Achlya. The genus Achlya appears polyphyletic,
      corroborating more or less the three known subgroups, defined by their sexual
      spore type (eccentric, centric and subcentric). The achlyoid type of spore
      dehiscence, shared by Aphanomyces and Achlya genera, is shown to be an ancestral
      character. The saprolegnioid, dictyoid and thraustothecoid types of spore
      dehiscence are derived characters but their relative evolutionary positions are
      not resolved.

PMID- 10959567
TI  - The relationship between transport kinetics and glucose uptake by Saccharomyces
      cerevisiae in aerobic chemostat cultures.
AB  - The steady-state residual glucose concentrations in aerobic chemostat cultures of
      Saccharomyces cerevisiae ATCC 4126, grown in a complex medium, increased sharply
      in the respiro-fermentative region, suggesting a large increase in the apparent
      kS value. By contrast, strain CBS 8066 exhibited much lower steady-state residual
      glucose concentrations in this region. Glucose transport assays were conducted
      with these strains to determine the relationship between transport kinetics and
      sugar assimilation. With strain CBS 8066, a high-affinity glucose uptake system
      was evident up to a dilution rate of 0.41 h(-1), with a low-affinity uptake
      system and high residual glucose levels only evident at the higher dilution
      rates. With strain ATCC 4126, the high-affinity uptake system was present up to a
      dilution rate of about 0.38 h(-1), but a low-affinity uptake system was discerned
      already from a dilution rate of 0.27 h(-1), which coincided with the sharp
      increase in the residual glucose concentration. Neither of the above yeast
      strains had an absolute vitamin requirement for aerobic growth. Nevertheless, in
      the same medium supplemented with vitamins, no low-affinity uptake system was
      evident in cells of strain ATCC 4126 even at high dilution rates and the steady
      state residual glucose concentration was much lower. The shift in the relative
      proportions of the high and low-affinity uptake systems of strain ATCC 4126,
      which might have been mediated by an inositol deficiency through its effect on
      the cell membrane, may offer an explanation for the unusually high steady-state
      residual glucose concentrations observed at dilution rates above 52% of the wash
      out dilution rate.

PMID- 10959568
TI  - Ascospore aggregation and oxylipin distribution in the yeast Dipodascopsis
      tothii.
AB  - Upon cultivation of the yeast Dipodascopsis tothii in its sexual stage, small
      ascospores are released individually from the ascus tip, which then assemble in
      sheathed cluster balls. In contrast to Dipodascopsis uninucleata, this yeast
      produced smooth bean shaped ascospores with sheath-like appendages that assemble
      in a disordered sheathed ball of ascospores outside the ascus. Strikingly, upon
      release, the ascus tip contained 3-hydroxy oxylipins, while the released
      ascospore clusters contained little or no 3-hydroxy oxylipins as indicated by
      immunofluorescence microscopy. In D. uninucleata, these oxylipins are
      concentrated on the spore surface and interspore matrix, but not on the ascus
      tip.

PMID- 10959569
TI  - Prevalence and expression of enterotoxins in Bacillus cereus and other Bacillus
      spp., a literature review.
AB  - Members of the Bacillus genus are ubiquitous soil microorganisms and are
      generally considered harmless contaminants. However, a few species are known
      toxin producers, including the foodborne pathogen, B. cereus. This species
      produces two distinct types of foodborne illness, the emetic (vomit-inducing)
      syndrome, associated with consumption of toxin in cooked rice dishes, and the
      diarrheal illness seen occasionally following consumption of contaminated meats,
      sauces, and certain dairy products. In the latter case, illness results from the
      production of enterotoxins by vegetative cells in the small intestine of the
      host. In dairy products, the occurrence of Bacillus spp. is inevitable, and the
      spore-forming ability of this organism allows it to easily survive
      pasteurization. Many strains have been shown to grow and produce enterotoxin in
      dairy products at refrigeration temperatures. Evaluation of toxin gene presence
      and toxin expression in Bacillus spp. other than B. cereus has not been
      thoroughly investigated. However, the presence of natural isolates of Bacillus
      spp. harboring one or more enterotoxin gene(s) and subsequent demonstration of
      conditions which may support toxin expression holds crucial importance in the
      food safety arena.

PMID- 10959570
TI  - A novel oxylipin-associated 'ghosting' phenomenon in yeast flocculation.
AB  - Research on the distribution of oxylipins (3-hydroxy fatty acids) in flocculant
      strains of the yeast Saccharomyces cerevisiae led to the uncovering of a novel
      'ghosting' phenomenon observed during assumed lectin-mediated aggregation. We
      found that intracellular oxylipin-containing osmiophilic layers migrate through
      yeast cell walls in a 'ghostlike' fashion without visually affecting the cell
      wall structure or the layers. This migration resulted in the binding of these
      layers to cell walls of adjacent cells. Consequently, 'ghosting' seems a
      prerequisite for flocculation to occur. However, 'ghosting' alone may not be
      sufficient to ensure flocculation.

PMID- 10959571
TI  - Molecular mobility of the paracetamol amorphous form.
AB  - The purpose of this paper is to study the molecular mobility of paracetamol
      molecules in their amorphous state below the glass transition temperature (Tg) in
      order to evaluate the thermodynamic driving force which allows the amorphous form
      to recrystallize under different polymorphic modifications. Samples were aged at
      temperatures of -15, 0, 6, and 12 degrees C for periods of time from 1 h to a
      maximum of 360 h. The extent of physical aging was measured by a DSC study of
      enthalpy recovery in the glass transition region. The onset temperature of glass
      transition was also determined (Tg). Enthalpy recovery (deltaH) and change in
      heat capacity (deltaCp) were used to calculate the mean molecular relaxation time
      constant (tau) using the empirical Kohlausch-Williams-Watts (KWW) equation.
      Enthalpy recovery and onset glass transition temperature increased gradually with
      aging and aging temperatures. Structural equilibrium was reached experimentally
      only at an aging temperature of 12 degrees C (Tg-10 degrees C), according to the
      deltaH(infinity) results. The experimental model used is appropriate only at
      lower aging temperatures, while at higher ones the complexity of the system
      increases and molecular polymorphic arrangement could be involved. When
      structural equilibrium is experimentally reached, molecules can be arranged in
      their lowest energy state, and the polymorphic form I formation is the one
      preferred.

PMID- 10959572
TI  - Four mono-tetrahydrofuran ring acetogenins, montanacins B-E, from Annona montana.
AB  - Four novel mono-tetrahydrofuran (THF) acetogenins, montanacins B-E (1-4), were
      isolated from the ethanolic extract of the leaves of Annona montana. The
      structures of 1-4 were established by spectroscopic methods and their absolute
      stereochemistries were determined by the advanced Mosher ester method. Montancins
      D (3) and E (4) bear a non-adjacent tetrahydropyran (THP) ring along with a THF
      ring and are the most unusual type of acetogenins discovered so far.

PMID- 10959574
TI  - Synthesis of 1-azabicyclo[3.3.0]octane derivatives and their effects as piracetam
      like nootropics.
AB  - A useful pharmaceutical intermediate, 5-nitromethyl-1-azabicyclo[3.3.0]octane
      (1), was prepared in one step from 1,7-dichloro-4-heptanone (4) under mild
      conditions. Catalytic hydrogenation of 1 over Raney Ni in the presence of sodium
      hydroxide afforded 5-aminomethyl-1-azabicyclo[3.3.0]octane (2) in high yield.
      Piracetam analogues 20-23, which were pyrrolidine derivatives involving a 1
      azabicyclo[3.3.0]octane ring, were synthesized. Pharmacological tests showed that
      N-[(1-azabicyclo[3.3.0]octan-5-yl)methyl]-2-oxo-1-pyrrolidineacetamid e (20)
      improves cerebral function.

PMID- 10959573
TI  - Quadranosides VI-XI, six new triterpene glucosides from the seeds of Combretum
      quadrangulare.
AB  - Six new triterpene glucosides, quadranosides VI-XI (1-6), belonging to three
      different [ursane- (1-4), oleanane- (5) and lupane-type (6)] triterpene classes,
      have been isolated from a MeOH extract of the seeds of Combretum quadrangulare
      KURZ (Combretaceae), together with nine known compounds, rosamutin (7), 28-O-beta
      D-glucopyranosyl-6beta,23-dihydroxytormentic acid (8), arjunetin (9),
      arjunglucoside II (10), combreglucoside (11), chebuloside II (12), vitexin (13),
      (+)-catechin (14) and (-)-epigallocatechin (15). The structures of these
      compounds were elucidated by spectroscopic analysis.

PMID- 10959575
TI  - Hydrolysis behavior of prednisolone 21-hemisuccinate/beta-cyclodextrin amide
      conjugate: involvement of intramolecular catalysis of amide group in drug
      release.
AB  - Prednisolone 21-hemisuccinate/beta-cyclodextrin (beta-CyD) amide conjugate was
      prepared by binding prednisolone 21-hemisuccinate covalently to the amino group
      of mono(6-deoxy-6-amino)-beta-CyD through amide linkage. Prednisolone 21
      hemisuccinate was intramolecularly transformed to prednisolone 17-hemisuccinate,
      and the parent drug, prednisolone, was slowly released from the 21-hemisuccinate
      with a half life of 69 h in pH 7.0 at 37 degrees C; the drug release at 25
      degrees C was less than 10% for 48 h. In sharp contrast, the hydrolysis of
      prednisolone 21-hemisuccinate/beta-CyD amide conjugate was significantly faster
      (half life of 6.50 min at 25 degrees C) and gave prednisolone and mono(6-deoxy-6
      succimino)-beta-CyD as products. The hydrolysis of the beta-CyD amide conjugate
      was subject to a specific-base catalysis in the alkaline region. The rapid
      hydrolysis of the conjugate can be ascribed to the involvement of an
      intramolecular nucleophilic catalysis of the amide group in the reaction. The
      succinic acid, bound to a drug through ester linkage at one carboxylic group and
      bound to a pro-moiety through amide linkage at another carboxylic group, may be
      useful as a spacer for construction of the immediate release type prodrugs of
      CyDs.

PMID- 10959576
TI  - Studies on antihypertensive agents with antithrombotic activity. 2. Syntheses and
      pharmacological evaluation of pyrrolo[2,3-c]azepine derivatives.
AB  - As an extension of our previous investigation, a series of 7
      aminoalkylpyrrolo[2,3-c]azepine derivatives was synthesized and evaluated as
      alpha1-adrenergic- and serotonin 2 (5-HT2)-receptor antagonists, with the aim of
      finding a novel potent antihypertensive agent with both activities. Among the
      compounds obtained in this study, (E)-1-ethyl-7-[3-[4-(4-fluorophenyl)piperazin-1
      yl]propyl]-4-hy droxyimino-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-on e (16d)
      displayed potent alpha1-adrenoceptor blocking activity (pA2=7.83+/-0.20) and 5
      HT2-receptor blocking activity (pA2=9.47+/-0.17) in isolated guinea pig arteries.
      At 3 mg/kg oral administration, compound 16d exhibited antihypertensive activity
      more potent than that of doxazosin in deoxycorticosterone acetate (DOCA)-salt
      hypertensive dogs. Furthermore, this compound reduced the rate of mouse acute
      pulmonary thromboembolytic death induced by collagen and serotonin at oral doses
      of 0.3 mg/kg or more, and its effect lasted for at least 6 h at 3 mg/kg.

PMID- 10959577
TI  - The effect of phenyl substituents on the release rates of esterase-sensitive
      coumarin-based prodrugs.
AB  - A coumarin-based prodrug system has been recently developed in our laboratory for
      the preparation of esterase-sensitive prodrugs of amines, peptides, and
      peptidomimetics. The drug release rates from this prodrug system were found to be
      dependent on the structural features of the drug moiety. In certain cases, the
      release can be undesirably slow for drugs that are secondary amines with
      relatively high pKa's. Aimed at finding ways to manipulate the release rates to
      suit the need of different drugs, we have examined the effect of the phenyl ring
      substitutions on the release kinetics of such prodrugs and found that
      appropriately positioned alkyl substituents on the phenyl ring could help to
      facilitate the release by as much as 16-fold. Therefore, introduction of alkyl
      substituents on the phenyl ring should allow us to manipulate the release rates
      and, therefore, time profiles for different drugs.

PMID- 10959578
TI  - Synthesis and systemic fungicidal activity of silicon-containing azole
      derivatives.
AB  - A new series of azole derivatives containing silicon were synthesized and
      evaluated for fungicidal activity against rice sheath blight by submerged
      application. Among them, 2-(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3
      trimethylsilylpr opan-2-ol (9a) exhibited satisfactory efficacy at 12.5 grams per
      10 ares.

PMID- 10959579
TI  - On-line monitoring of granule growth in high shear granulation by an image
      processing system.
AB  - A novel system has been developed to continuously monitor granule growth in a
      high shear granulation. The system consists of an image processing system and a
      particle image probe comprising a CCD camera, lighting unit and air purge system.
      Segregation during powder mixing was investigated experimentally and the optimal
      positioning of the probe was determined. High shear granulation was conducted
      using pharmaceutical powders, and granule size and product's yield of various
      size ranges were continuously measured by the developed system. Sieve analysis of
      the granulated products sampled out during the granulation was simultaneously
      conducted, and the obtained data was compared with that by the on-line image
      processing system. An extremely close relationship could be found between both
      data, proving that the developed system could monitor the granule growth
      accurately and continuously throughout the granulation. An on-off control system
      was developed to control the granulation process, and the performance of the
      system was confirmed.

PMID- 10959580
TI  - Synthetic studies on glycosphingolipids from protostomia phyla: synthesis of a
      glycosphingolipid analogue from the parasite Spirometra erinacei.
AB  - Novel neutral glycosphingolipids isolated from the plerocercoids of a tapeworm,
      Spirometra erinacei, may be expected to be involved in host-parasite
      interactions. We have synthesized this glycosphingolipid analogue containing 2
      branched fatty alkyl residue in place of ceramide. Glycosylation of nonreducing
      end trisaccharide derivative 15 with the reducing-end disaccharide derivative 17
      in the presence of trimethylsilyl triflate (TMSOTf) gave the desired
      oligosaccharide derivative in good yield. The fully per-O-acylated 2
      (trimethylsilyl)ethyl glycoside 19 was converted to glycosylimidate 20, which was
      condensed with 2-(tetradecyl)hexadecanol and subsequently deacylated to give the
      target glycosphingolipid analogue 22.

PMID- 10959581
TI  - Structure-activity relationships of neuromedin U. IV. Absolute requirement of the
      arginine residue at position 7 of dog neuromedin U-8 for contractile activity.
AB  - To examine the role of both Arg residues at positions 5 and 7 of dog neuromedin U
      8 (d-NMU-8; pGlu1-Phe-Leu-Phe-Arg5-Pro-Arg7-Asn8-NH2) for smooth muscle
      contractile activity on isolated chicken crop, d-NMU-8 analogs were synthesized
      where either Arg residue was systematically replaced by various amino acids [X:
      Ala, Thr, Glu, Gln, Lys, Orn, His, citrulline (Cit) or homoarginine (Har)]. All
      [X5]-d-NMU-8, except for [Glu5]- and [Des-Arg5]-d-NMU-8, were full agonists,
      although their affinities to NMU receptors were decreased. No [X7]-d-NMU-8 showed
      contractile activity even at concentrations of 10(-5) mol/l, except for [Har7]-d
      NMU-8, which retained weak biological activity. These analogs had no antagonistic
      activity against porcine neuromedin U-8 (p-NMU-8). The results revealed that Arg7
      of d-NMU-8 is indispensable for receptor binding and activation to induce smooth
      muscle contraction, and the guanidino group of the side chain at position 7, but
      not at position 5, is strictly recognized by NMU receptors in the chicken crop.

PMID- 10959582
TI  - Aldol condensation versus conjugate addition: intramolecular cyclization using a
      combination of Lewis acid and 1,2-diol.
AB  - The reactivity of 3-substituted 4-methyl-4-(3-oxobutyl)-2-cyclohexen-1-ones (1)
      in the presence of a combination of a Lewis acid and a 1,2-diol was studied. The
      results suggest several factors that influence 6-membered ring formation,
      including two types of intramolecular aldol reaction and intramolecular 1,4
      addition, due to the C3-substituent, Lewis acid, and the presence of diol. In
      this study, novel methodology to prepare two types of decalin skeleton could be
      developed.

PMID- 10959583
TI  - Synthesis of decalin type chiral synthons based on enzymatic function.
AB  - Enzymatic monobenzoylation of (+/-)-2-hydroxy-decahydro-5,5,8a-trimethyl-1
      naphthalenemethano l derivatives (1-4) using vinyl benzoate in organic solvent
      gave the optically active diols (1-4) and monobenzoates (16-19). The enantiomeric
      excess (ee) of the enzymatic reaction products were found to be in the range of
      11% to 49%. On the other hand, enzymatic hydrolysis of the acetoxybenzylidene
      acetal (+/-)-25d, e was found to give more than 90% ee of (10aS)-25d, e in
      moderate yield. Finally, the 90% ee of (10aS)-25e was converted to the 90% ee of
      the desired (8aS)-1.

PMID- 10959584
TI  - 6S,8R-Stereochemistry of the C27- and C29-alkane-6,8-diols isolated from three
      compositae flowers.
AB  - The Deltadelta (deltaS-deltaR) values for the C-1 methyl 1H signals in the 1H-NMR
      spectroscopy of the bis-MTPA esters of four synthetic stereoisomers of alkane-6,8
      diols, viz., bis-MTPA esters of (6S,8R)-C27- (1a) and C29- (3a) (Deltadelta = 
      0.05 ppm), (6R,8S)-C27- (2a) and C29- (4a) (Deltadelta = +0.05 ppm), (6S,8S)-C27-
      (5a) (Deltadelta = -0.01 ppm), and (6R,8R)-C27- (6a) (Deltadelta = +0.01 ppm)
      alkane-6,8-diols, made it possible to differentiate unequivocally among the four
      stereoisomers. This allowed the determination of the (6S,8R)-stereochemistry
      (Deltadelta = -0.05 ppm for the bis-MTPA esters) for the natural C27- and C29
      alkane-6,8-diols isolated from the flowers of three Compositae plants, Carthamus
      tinctorius, Cynara cardanclus, and Taraxacum platycarpum.

PMID- 10959585
TI  - Ichthyotoxic phloroglucinol derivatives from Dryopteris fragrans and their anti
      tumor promoting activity.
AB  - Two new ichthyotoxic compounds, aspidin PB (8) and dryofragin (9), along with
      three known phloroglucinol derivatives (1-3) and five terpenoids, were isolated
      from the whole herbs of Dryopteris fragrans by toxicity-directed fractionation
      using Oryzias latipes (Japanese name; medaka). The structures of the new
      compounds were determined by spectroscopic methods including 2D NMR techniques.
      Amongst the isolates, aspidin PB (8), dryofragin (9), and 1-5 exhibited potent
      ichthyotoxic activity against medaka with a median tolerance limit (TLm after 24
      h) of 1.2-4.3 microg/ml. These compounds which are toxic to fish also had a
      potent inhibitory effect on the activation of Epstein-Barr virus early-antigen
      (EBV-EA) induced by tetradecanoyl phorbol 13-acetate, which is an in vitro short
      term assay for anti-tumor promoting agents. Aspidin BB (2) and albicanol (4),
      which exhibited strong inhibitory effects on the EBV-EA activation, significantly
      suppressed an in vivo two-stage carcinogenesis on mouse skin.

PMID- 10959586
TI  - Reactions of grignard reagents with bis- or mono-phosphonium ions in situ
      generated from Bu3P and dicarboxylic acid dichlorides or omega-ethoxycarbonyl
      alkanoyl chlorides as a novel method to obtain diketones and ketoesters.
AB  - Reactions of Grignard reagents with bis-phosphonium or mono-phosphonium ions in
      situ generated from BusP and ClCO(CH2)nCOCl (5) or ClCO(CH2)nCO2Et (13) as a tool
      for preparation of symmetrical diketones or ketoesters were examined. Addition of
      Bu3P (2.0 eq) to a THF solution of 5 (n=2) at -40 degrees C followed by addition
      of n-BuMgCl (2.0 eq) gave the corresponding diketone in good yield. When a
      mixture of BusP and the Grignard reagent (2.0 eq each) was added to the
      dichloride solution at the same temperature, a better result was obtained. The
      latter method not with PhMgBr but with n-BuMgCl or MeMgBr was shown to be useful
      for preparation of symmetrical alkanediones and keto alkanoates from various 5
      (n=2-6) and 13 (n=2 or 3), respectively. For synthesis of alpha-diketones or
      alpha-ketoesters, only PhMgBr entered the reaction, although the yields were not
      satisfactory. Addition of a mixture of Bu3P (2.0 eq), MeMgBr (1.0 eq) and BuMgCl
      (1.0 eq) to a THF solution of 5 (n=4) at -40 degrees C afforded a mixture of 2,7
      undecanedione and the corresponding two symmetrical diketones, with the yield of
      the unsymmetrical diketone being 36%.

PMID- 10959587
TI  - Five secoiridoid glucosides esterified with a cyclopentanoid monoterpene unit
      from Jasminum nudiflorum.
AB  - Phytochemical study of the stems of Jasminum nudiflorum has led to the isolation
      of five new secoiridoid glucosides, jasnudiflosides D (1) and E (2) and
      nudiflosides A-C (3-5). The structures of these compounds were elucidated on the
      basis of chemical and spectroscopic evidence.

PMID- 10959588
TI  - Evidence for the degradation of maleate moiety in chlorpheniramine maleate
      solution using a stability-indicating HPLC method.
AB  - The degradation phenomenon of maleate moiety of chlorpheniramine maleate in
      solution has been demonstrated by means of a peculiar ion-pair HPLC method
      developed by the authors, which permits the simultaneous determination of
      chlorpheniramine and maleate. A commercial cough drug containing chlorpheniramine
      maleate was dissolved in water with m-hydroxybenzoic acid as an internal
      standard, and then kept for several days at room temperature. It was recognized
      that the maleate content in the drug solution had gradually decreased, whereas
      chlorpheniramine content had not decreased. A simple solution of maleic acid was
      also kept for several days at room temperature, and it was also recognized that
      the maleate content in the solution preserved at the same concentration as the
      solution of the commercial cough drug had gradually decreased, and the percent of
      remaining maleate reached zero. The degraded peaks on HPLC chromatogram were not
      detected at all by UV detector, and the disappearance of maleate was ascertained
      by GC-MS. No detectable example of maleate of chlorpheniramine maleate in a
      commercial cough syrup has suggested that maleate moiety of chlorpheniramine
      maleate decomposed to carbon dioxide.

PMID- 10959589
TI  - Influence of the conformation of methoxy-(2-naphthyl)acetates (2NMA esters) on
      their chemical reactions.
AB  - An SN2 reaction (NaI) of 1,7-di(methanesulfoxyl)heptadien-4-yl methoxy-(2
      naphthyl)acetate and a tributyltin hydride reduction of 1,7-diiodo-4-yl methoxy
      (2-naphthyl)acetate (2NMA) is crucial for determination of the absolute
      configuration of secondary alcohols.

PMID- 10959590
TI  - Six new compounds from the heartwood of Diospyros maritima.
AB  - Six new compounds, diospyrolide (1), diospyrolidone (2), diethyl (2R)-malate (3),
      3-(E)-coumaroylbetulin-28-yl ethyl nonanedioate (4), 3-(E)-coumaroylbetulin-28-yl
      ethyl succinate (5), and 3-(E)-coumaroylbetulin-28-yl ethyl (2R)-2
      hydroxysuccinate (6), have been isolated from the heartwood of Diospyros
      maritima. Compounds 1 and 2 are novel trinorlupanes, and 4, 5 and 6 are lupane
      derivatives. Their structures were determined using spectral and chemical
      methods.

PMID- 10959591
TI  - Formation of 17beta-alkoxy-16-keto steroids by reaction of 16alpha-hydroxy-17
      keto and 17beta-hydroxy-16-keto steroids with trimethylsilyl iodide in the
      presence of alkyl alcohols.
AB  - 16Alpha-hydroxy-17-keto steroids, 1, 3, and 8, and their 17beta-hydroxy-16-keto
      isomers, 4, 5, and 9, were transformed into the corresponding 17beta-alkoxy-16
      keto derivatives on treatment with trimethylsilyl iodide (TMSI) in the presence
      of alkyl alcohol in CHCl3 in poor to high yields.

PMID- 10959592
TI  - Studies on the constituents of Anaxagorea luzonensis A. GRAY.
AB  - Five new xanthones, 1,3,6-trihydroxy-5-methoxy-4-prenylxanthone (1), 1,3,5
      trihydroxy-6-methoxy-2-prenylxanthone (2), 1,3,5-trihydroxy-4-(3-hydroxy-3
      methylbutyl) xanthone (3), 1,3,6-trihydroxy-4-prenylxanthone (4), 3,6-dihydroxy
      1,5-dimethoxyxanthone (5) and one new flavonoid, 3,5,7,4'-tetrahydroxy-2'
      methoxyflavone (6) along with seven known xanthones and seven known flavonoids
      were isolated from the bark of Anaxagorea luzonensis A. GRAY and their chemical
      structures were determined by means of chemical and spectral studies. Almost all
      flavonoids and one xanthone (13) showed antioxidant activity.

PMID- 10959593
TI  - Three oligosaccharide esters, telephioses A-C, from Polygala telephioides.
AB  - Three new oligosaccharide esters named telephioses A-C, were isolated from
      Polygala telephioides WILLD. and their structures were characterized by
      spectroscopic data.

PMID- 10959594
TI  - Major metabolites of ginseng sapogenins formed by rat liver microsomes.
AB  - Incubation of ginseng sapogenins with microsomes from rat liver resulted in
      formation of their 20,24-epoxides as major metabolites. Identification of the
      metabolites was performed by HPLC, FAB-MS and EI-MS.

PMID- 10959595
TI  - Novel biphenyl ether lignans from the rhizomes of Curcuma chuanyujin.
AB  - Three new biphenyl ether lignans, 1, 2 and 3, were isolated from the rhizomes of
      Curcuma chuanyujin along with curcuminoid compounds 4, 5 and 6 and their chemical
      structures were determined to be 1-feruloyloxy-2-methoxycinnamic acid, 1
      feruloyloxy cinnamic acid and (1-p-hydroxycinnamoyl) cinnamic acid by means of
      spectral evidence. The latter three known substances showed antioxidant activity.

PMID- 10959596
TI  - A new practical strategy for the synthesis of long-chain phosphopeptide.
AB  - A new practical strategy has been developed for the synthesis of long-chain
      phosphopeptide. Both the 2-chlorobenzyloxycarbonyl (CIZ) group for Lys and methyl
      (Me) for phosphoamino acids remained intact, while other commonly used side-chain
      protecting groups were cleaved quantitatively, during the reaction using a highly
      acidic trifluoromethanesulfonic acid (TFMSA)-based reagent system (High TFMSA:
      TFMSA-TFA-m-cresol=1:9:1, v/v). Selective deprotection of the CIZ and Me group
      containing protected phosphopeptide resin with the High TFMSA gave a partially
      protected phosphopeptide fragment suitable for thioester-mediated fragment
      condensation. A deprotection protocol of the 9-fluorenylmethyloxycarbonyl (Fmoc)
      group, which evades significant side reaction toward the protected phosphoamino
      acid, was also developed. These two new findings enabled us to synthesize long
      chain phosphopeptide via thioester-mediated fragment condensation.

PMID- 10959597
TI  - Labdane diterpenoids from Marrubium globosum ssp. globosum.
AB  - A new labdane type diterpenoid, marrubiglobosin, was isolated from the aerial
      parts of Marrubium globosum ssp. globosum together with the known diterpenoids,
      marrubiin and marrubinone B. The structure of this new compound was elucidated by
      spectral methods.

PMID- 10959598
TI  - Chemiluminescence derivatization of methylglyoxal using 2-aminonicotinic acid.
AB  - To develop a sensitive and selective chemiluminometric method for the
      determination of methylglyoxal, we used 2-aminonicotinic acid as the
      chemiluminescence derivatization reagent. 2-Aminonicotinic acid reacts with
      methylglyoxal in an acidic solution at 37 degrees C for 4 h and gave a
      chemiluminescence in N,N'-dimethylformamide containing sodium tert-butoxide. The
      detection limit (blank intensity plus three-times its standard deviation of
      methylglyoxal) for methylglyoxal is 233 fmol in the reaction mixture.

PMID- 10959599
TI  - Biotransformation of a C-glycosylflavone, abrusin 2''-O-beta-D-apioside, by human
      intestinal bacteria.
AB  - After anaerobic incubation of abrusin 2''-O-beta-D-apioside (1) with a human
      fecal suspension, five metabolites were isolated and identified as abrusin (2), 1
      (2',6'-dihydroxy-3',4'-dimethoxyphenyl)-3-(4''-hydroxyphenyl)propan-1- one (5),
      5,6-dimethoxybenzene-1,3-diol (6), 3-(4'-hydroxyphenyl)propionic acid (7) and 3
      phenylpropionic acid (8). However, methyl ether derivatives of abrusin (4'-O
      methylabrusin and 4'-O-, 5-O-dimethylabrusin) resisted degradation under the same
      conditions.

PMID- 10959600
TI  - Two new acylated flavonol glycosides from Vicia amurensis.
AB  - Two new acylated flavonol glycosides, named amurenosides A and B, together with
      quercetin 3-(2,6-di-O-alpha-rhamnopyranosyl-beta-galactopyranoside), have been
      isolated from the whole plant of Vicia amurensis. Their structures were
      elucidated as quercetin 3-O-alpha-L-(3-feruloylrhamnopyranosyl)(1-->6)-[alpha-L
      rhamnopyra nosyl(1-->2)]-beta-D-galactopyranoside and quercetin 3-O-alpha-L-(2
      feruloylrhamnopyranosyl)(1-->6)-[alpha-L-rhamnopyra nosyl(1-->2)]-beta-D
      galactopyranoside on the basis of various NMR techniques, FAB mass spectrometry
      and chemical reactions.

PMID- 10959601
TI  - Three novel cyclospirobifuranocoumarins, cyclorivulobirins A-C, from
      Pleurospermum rivulorum.
AB  - Three novel cyclospirobifuranocoumarins, cyclorivulobirins A-C (1-3), were
      isolated from the underground part of Pleurospermum rivulorum. They are
      characterized as three stereoisomers having a different configuration at the C-2
      and C-2' position resulting from the condensation of two heraclenol units,
      respectively, on the basis of chemical and spectral methods.

PMID- 10959602
TI  - Public health--the vision and the challenge. An attempt to analyse the issues and
      possible solutions.

PMID- 10959603
TI  - Association of lifestyle with serum lipid levels: a study of middle-aged Japanese
      men.
AB  - Cross-sectional associations between lifestyle and serum lipid levels were
      examined in 1591 Japanese male office workers aged 35 to 59 years in Osaka,
      Japan. From multiple linear regression analyses, significant correlates with low
      density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)
      cholesterol, and Log triglyceride levels and the ratio of LDL cholesterol to HDL
      cholesterol were, in the order of relative importance: BMI, alcohol intake
      (negative) and age for LDL cholesterol level; BMI (negative), cigarette smoking
      (negative), alcohol intake, consideration for nutritional balance, hours of brisk
      walking, hours of walking at an ordinary pace and physical exercise for HDL
      cholesterol level; BMI, cigarette smoking, consideration for nutritional balance
      (negative), hours of work (negative), alcohol intake and coffee drinking
      (negative) for Log triglyceride level; and BMI, alcohol intake (negative),
      cigarette smoking, consideration for nutritional balance (negative), age, hours
      of brisk walking (negative) and the frequency of snack intake between meals for
      the ratio of LDL cholesterol to HDL cholesterol. Our data suggest that obesity,
      cigarette smoking and snack intake between meals are atherogenic whereas alcohol
      consumption, consideration for nutritional balance and walking long hours,
      especially at a brisk pace, are anti-atherogenic in middle-aged Japanese men.

PMID- 10959604
TI  - Leisure-time physical activity and related lifestyle characteristics among middle
      aged Japanese. Japan Lifestyle Monitoring Study Group.
AB  - The present study describes leisure-time physical activity status and related
      lifestyle factors in middle-aged Japanese. Data were obtained from 1,893 (905
      men, 988 women) participants aged 40-69 years who had either been selected from a
      public registry or who had visited a healthcare facility. Subjects responded to a
      self-administered questionnaire and were interviewed using an assessment method
      for leisure-time and on-the-job physical activity within the last 12 months by
      trained interviewers. According to the leisure-time physical activity score, men
      and urban residents tended to engage in more leisure-time physical activity than
      did women and rural residents, respectively. Leisure-time physical activity
      tended to be inversely associated with on-the-job physical activity in all cases
      aside from women in urban regions, and also to be associated with higher levels
      of education in rural regions. Subjects engaging in more leisure-time physical
      activity had higher odds ratios of certain lifestyle factors, indicating a
      healthy lifestyle that included a variety of foods in their diet and a subjective
      sense of wellness in both men and women, in addition to non-smoking and drinking
      milk in men. These results suggested that leisure-time physical activity is
      influenced by socio-environmental factors, and that it is accompanied by other
      healthy behavior.

PMID- 10959605
TI  - Effectiveness of interferon therapy for reducing the incidence of hepatocellular
      carcinoma among patients with type C chronic hepatitis.
AB  - STUDY PURPOSE: To evaluate the effect of interferon treatment for reducing the
      incidence of hepatocellular carcinoma among patients with type C chronic
      hepatitis. METHODS: Retrospective cohort study was conducted on 923 patients with
      type C chronic hepatitis, who were identified through databases of Osaka Medical
      Center for Cancer and Cardiovascular Diseases. Two hundred and twenty-four of
      those had undergone interferon treatment, while the other 699 patients had not.
      Kaplan-Meier method and the proportional hazards model were used for statistical
      analysis. RESULTS: Five-years' cumulative incidence of hepatocellular carcinoma
      was 2.2% among the interferon treated patients, while 9.5% among the interferon
      untreated. Difference between the 2 curves of the cumulative incidence was
      statistically significant (p=0.0015). After adjustment for possible confounders,
      hazard rate ratio of hepatocellular carcinoma was 0.31 in the interferon treated
      group, significantly lower than that in the untreated (p=0.015). Hazard rate
      ratio for death from causes other than hepatocellular carcinoma and liver
      diseases was also lower among the interferon treated group than that among the
      untreated, although not significant. CONCLUSIONS: Interferon treatment is
      suggested to reduce the risk of hepatocellular carcinoma among patients with type
      C chronic hepatitis, and not to increase the risk for death from causes other
      than hepatocellular carcinoma and liver diseases.

PMID- 10959606
TI  - The characteristics of fatigue symptoms and their association with the life style
      and the health status in school children.
AB  - In order to evaluate the characteristics of fatigue symptoms and their
      association with the life style and the health status, we examined using data
      accumulated by the longitudinal surveys from 1992 to 1998, in 118 six-year
      primary school children and 129 second-year junior high school children. The
      complaints of "drowsiness and dullness", such as "become drowsy" (71%), "give a
      yawn" (59%) and "want to lie down" (51%), respectively, were most frequently
      observed. The proportion of these complaints was high before the first morning
      class, but decreased when the children leave school. Notably, the complaints of
      "difficulty in concentration" annually have increased. Children with undesirable
      eating habits, particularly those who often eat salty foods, or poor life style,
      such as staying up late at night tended to have more complaints of fatigue
      symptoms. By correlation analysis, these complaints were significantly related to
      the obesity degree, blood pressure, HDL cholesterol and atherogenic index. These
      results support the hypothesis that fatigue symptoms increase or are associated
      with life style and health status. Consequently, it is necessary to improve the
      life style such as dietary habits and rhythm of life for the reduction of fatigue
      symptom.

PMID- 10959607
TI  - Functional transitions in instrumental activities of daily living among older
      Japanese.
AB  - We observed functional transitions in instrumental activities of daily living
      (IADL) over one year among older Japanese and examined factors influencing the
      deterioration of each IADL. The sources of the study were the first and second
      panel studies of the Saku Longitudinal Study on Aging, which were done in 1988
      and 1989. The study subjects were those participants aged 70 or older. Five IADL
      items--using public transportation, shopping for daily necessities, preparing
      meals, paying bills, and managing deposits--were measured in each survey.
      Deterioration of each IADL item was examined in relation to demographic
      characteristics such as age, sex, occupational status, living arrangements, and
      educational status. Of the effective baseline cohort (n = 5,559), 4,892 responded
      in the second survey (response rate 88%). Over 80% of the respondents who were
      initially independent in each IADL item remained independent in the second
      survey. Multiple logistic regression analyses revealed that greater age, having
      no occupation, and living with children at the baseline were associated with
      deterioration in each item of IADL. Lower educational status was associated with
      deterioration in each item of IADL except preparing meals. This study indicates
      that being engaged in work, living separately from children, and having higher
      educational status are strongly correlated with remaining independent in IADL for
      older people aged 70 or older.

PMID- 10959608
TI  - Tracking of cardiovascular risk factors and a cohort study on hyperlipidemia in
      rural schoolchildren in Japan.
AB  - A cohort study was conducted to explore the tracking stability of cardiovascular
      risk factors and relative risk (RR) of factors relating hyperlipidemia in
      children. The percentages of children remaining persistently at high risk over a
      four-year tracking were as follows: body mass index (BMI) 65.0%, total
      cholesterol (T-c) 60.6%, atherogenic index (AI) 56.4%, high density lipoprotein
      cholesterol (HDL-c) 50.7%, systolic blood pressure (SBP) 44.2% and diastolic
      blood pressure (DPB) 39.6%. The order of correlation coefficients over four years
      was BMI > AI > HDL-c > T-c > SBP > DBP and these coefficients in boys were
      slightly higher than those in girls. The relative risk (RR) of BMI for AI > or =
      3 was elevated (RR=4.36, 95% CI: 1.3-14.1). The incidence and RR for AI > or = 3
      increased along with the addition of the selected risk factor number. The RR in
      children with three selected risk factors rose to 8.39 ( 95% CI: 1.2-38.7 ). The
      stability of tracking was better for BMI, T-c, AI and HDL-c. As the number of
      multiple factors increased, so did the RR of higher AI in childhood. These
      results suggest that preventive activities for hyperlipidemia should be focused
      on children with multiple cardiovascular risk factors.

PMID- 10959609
TI  - Health effects of chronic exposure to polychlorinated dibenzo-P-dioxins (PCDD),
      dibenzofurans (PCDF) and coplanar PCB (Co-PCB) of municipal waste incinerator
      workers.
AB  - A national survey of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans
      (PCDF) in emission gases from the municipal waste incinerators in 1997 revealed
      that the Nose Bika Center was heavily contaminated by PCDF. Ninety-four workers
      underwent a physical examination, and blood biochemistry, lymphocyte marker, and
      NK activity studies were carried out, along with blood dioxin measurements.
      Information on working history, life-style, and dietary habits was obtained by
      questionnaire and interview. The blood dioxin levels were as follows. The median
      TEQ of dioxins was 39.7 pg I-TEQ/g lipid, and the range was 13.3 to 805.8. The
      median 2,3,7,8-TCDD concentration was 3.9 pg TEQ/g lipid, and the range was <1 pg
      TEQ/g lipid (one case) to 13.4 pg TEQ/g lipid. The median TEQ of coplanar PCB was
      10.8 pg I-TEQ/g lipid, and the range was 3.1 to 54.2 pg TEQ/g lipid. The congener
      specific distribution was quite similar to that in soil around incinerator and
      waste in the factory. The relationship between dioxin concentrations and work
      history in the factory showed that the fluidized incinerator and fly ash
      treatment areas were high-risk work areas. Correlation analyses between body
      burden, PCDD/PCDF TEQ, Co-PCB TEQ and various laboratory data showed significant
      positive correlations between dioxin levels and GGT, total protein, uric acid and
      calcium, and a negative correlation with Fe. However, these correlations
      disappeared as a result of multivariate analysis adjusted for age, smoking
      status, and alcohol drinking. Increased NK activity and lower response to PHA
      stimulation remained significant even after adjusting for age. History of
      hyperlipidemia and allergy had significantly increased odds ratios. A study on
      the risk to other workers in the same type of incinerators is under way. Health
      effects of chronic exposure mainly to PCDF will be clarified by follow-up.

PMID- 10959610
TI  - The psychological characteristics of tobacco dependence in a rural area of Japan.
AB  - To investigate the psychological characteristics of smoking and tobacco
      dependence, a questionnaire survey was conducted of 2,051 consenting adults aged
      21 to 65 years from the total population of a town in Akita Prefecture. Valid
      responses were received from 673 men and 818 women, for a total of 1,491 (72.7%).
      The questionnaires used were a tobacco dependence questionnaire, a personality
      questionnaire (the NEO Five-Factor Inventory: NEO-FFI), the WHO Subjective Well
      being Inventory (SUBI), and the 12-Item General Health Questionnaire (GHQ-12).
      Subjects who responded that they had smoked daily for more than one month before
      the day of the survey were considered smokers. There were 400 male (59.8%) and 39
      female (4.8%) smokers. Both male and female smokers were more extroverted than
      nonsmokers. Among smokers, there were 166 (41.5%) men and 19 (49%) women
      diagnosed as having a tobacco dependence of ICD-10. Among men, dependent smokers
      had a significantly higher score for Openness of the NEO-FFI and a lower score
      for Perceived III Health on the SUBI than nondependent smokers. Among smokers,
      128 (32.0%) men and 13 (33%) women met the ICD-10 criteria for tobacco
      withdrawal. Among male smokers, those with tobacco withdrawal had a significantly
      higher score for Neuroticism and Openness on the NEO-FFI and a lower score for
      Negative Affect on the SUBI than those with no withdrawal. These results suggest
      that there is a relationship between tobacco dependence and personality or
      negative emotions.

PMID- 10959611
TI  - The human behavioral and socioeconomic determinants of malaria in Bacan Island,
      North Maluku, Indonesia.
AB  - In eastern Indonesia, malaria control activities mainly depend on residual
      spraying but the situation is almost unchanged since the past decade.
      Understanding the socioeconomic and human behavior determinants is needed to
      implement an effective malaria control in accordance with the local condition and
      development. Hence we conducted an unmatched case control study. Two hundred
      samples were recruited from all, 11 villages surrounding the centre in Bacan
      Island, Maluku. For children aged 0 to 15 years old, the association of
      socioeconomic determinants: crowding and poor type of houses with malaria
      remained significant in the multivariate analysis. Meanwhile for persons above 15
      years old, younger persons and regular going outside at night remained
      significant in the multivariate analysis. And for persons above 15 years old, a
      higher proportion of controls (14%) than cases (4%) slept under mosquito net
      regularly. The Indonesia Family Program should be promoted. There was a better
      quality of life in small family. For persons above 15 years old, going outside at
      night should be discouraged because exposed to mosquito bites. The malaria
      control strategy use of effective personal, regular use of mosquito net could be
      used as a completion for the present activities. Considering the low malaria
      knowledge among samples, inhabitants should be enhanced the malaria knowledge on
      causation, transmission, prevention and to provide proper knowledge on residual
      spraying.

PMID- 10959612
TI  - Biomedical research productivity in Asian countries.

PMID- 10959613
TI  - Regular joint loading in youth assists in the establishment and strengthening of
      the collagen network of articular cartilage and contributes to the prevention of
      osteoarthrosis later in life: a hypothesis.

PMID- 10959614
TI  - The effects of nandrolone decanoate on bone mass and metabolism in ovariectomized
      rats with osteopenia.
AB  - The effects of nandrolone decanoate (ND) treatment on bone mass and metabolism
      were studied in ovariectomized (OVX) rats with osteopenia. The 6-month-old rats
      were divided into Sham (n = 12) and OVX (n = 24). The OVX rats were allowed to
      lose bone for 6 weeks. At 6 weeks post ovariectomy, the OVX rats were divided
      into two groups: (1) OVX + Vehicle and (2) OVX + ND. The effects of ND on bone
      mineral density (BMD), bone mineral content (BMC), and bone metabolism were
      studied by dual-energy X-ray absorptiometry (DXA) and biochemical markers
      including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum
      osteocalcin. After 24 weeks of treatment, histomorphometry of the right tibiae
      and the wet weight of the gastrocnemius and soleus skeletal muscles were also
      examined. Ovariectomy resulted in a significant increase in biochemical markers
      and a significant decrease in spine BMD (0.221+/-0.016g/cm2 in OVX group vs
      0.239+/-0.008g/cm2 in Sham group) and BMC (0.550+/-0.055g in OVX group vs 0.605+/
      0.042g in Sham group) at 6 weeks post ovariectomy. Spine BMD (0.227+/
      0.017g/cm2), femoral BMD (0.263+/-0.012g/ cm2), and bone density of femur
      (1.035+/-0.036g/cm3) in the OVX + ND group were significantly greater than those
      in the OVX + Vehicle group (0.204+/-0.013g/cm2 for spine BMD, 0.243+/-0.009g/cm2
      for femoral BMD, 0.938+/-0.06g/cm3 for bone density of femur) after 24 weeks of
      treatment. ND treatment decreased urinary Pyr and Dpyr significantly in OVX rats.
      Histomorphometric findings indicated that ND-treated rats had greater cancellous
      bone volume, greater trabecular number, greater trabecular thickness, and less
      trabecular separation than vehicle-treated OVX rats. OVX rats had greater wet
      weight of the gastrocnemius and soleus muscles than rats treated with ND. The
      data suggest that the effect of ND on bone mass is not influenced by the
      condition of the muscles in OVX rats. Our findings indicate that ND blocks
      further bone loss by inhibition of bone resorption in OVX rats with osteopenia.

PMID- 10959615
TI  - Alternation in bone components with increasing age of newborn rats: role of zinc
      in bone growth.
AB  - The effect of zinc on bone growth in newborn rats supplied with lactation by
      maternal rats was investigated. Newborn rats were killed between 1 and 35 days
      after birth. Increasing age caused a significant increase in zinc content,
      calcium content, and alkaline phosphatase activity in the femoral-diaphyseal and
      metaphyseal tissues, while the bone deoxyribonucleic acid (DNA) content was
      significantly decreased because of elevation of mineral content. Oral
      administration of zinc sulfate (2.0mg/100g body weight; four times at 24-h
      intervals) to maternal rats from 1 day after birth induced a significant increase
      in zinc, alkaline phosphatase activity, DNA, and calcium content in the femoral
      diaphyseal and metaphyseal tissues of newborn rats compared with those 7 or 14
      days old. The results indicate that the increase in bone components results from
      lactation with zinc-containing milk of maternal rats. The femoral-metaphyseal
      tissues of newborn rats obtained at 7 days after birth were cultured for 24h in a
      medium containing either vehicle or zinc sulfate (10(-6) to 10(-4) M) in vitro.
      Bone alkaline phosphatase activity and calcium and DNA content were significantly
      increased by zinc addition. These increases were completely prevented by the
      presence of dipicolinate (10(-3) M), a chelator of zinc ion, or cycloheximide
      (10(-6) M), an inhibitor of protein synthesis. The present study suggests that
      zinc plays a role in the development of bone growth in newborn rats.

PMID- 10959616
TI  - Quantitative analysis using the star volume method applied to skeleton patterns
      extracted with a morphological filter.
AB  - In this study, a morphological filter was combined with star volume analysis and
      applied to digital images to determine its potential usefulness in assessing
      trabecular structure. Three digital "geometric" test patterns (square, rectangle,
      circle) were created on a CRT (cathode ray tube). Each shape was arranged into
      five groups by size to yield 15 final "skeletal" patterns that were subsequently
      assessed with star volume analysis. Also, three digital X-ray images (background,
      soft tissue, bone block) were processed with a morphological filter to create
      three sets of 11 skeletal patterns each. These patterns were also assessed with
      star volume analysis and the ratio of extracted skeletal elements (in pixel
      numbers) to total pixel numbers was expressed as the pixel percentage. Star
      volume analysis was then applied to these digital skeletal images to yield the
      volume of extracted "skeletal" trabecular elements (Vsk) and the volume of
      nonskeletal (marrow space) elements (Vsp). The Vsk and Vsp were compared for all
      the different skeletal patterns. The pixel percentages were then compared to the
      star volume results for the X-ray test patterns. The Vsk decreased and Vsp
      increased as the number of operations (n) increased for both digital X-ray images
      and the geometric test patterns when the X-ray images were depicted by pixel
      percentages. Also, all true bone test patterns were clearly different both
      visually and quantitatively when compared to the noise skeletons extracted from
      background and soft tissue. Therefore, as Vsk was increased, so was connectivity.
      It can be concluded that the application of morphological filters and star volume
      analysis may be a useful tool in quantitatively determining the characteristics
      and continuity of trabecular skeletal structures. Further studies involving a
      larger number of bone samples and using models to compare measurements of
      calculated versus actual volume should reveal the true potential of this method
      for evaluating bone structure and its relationship to bone strength and also
      increase the tools available for evaluating bone diseases such as osteoporosis.

PMID- 10959617
TI  - Does bone design intend to minimize fatigue failures? A case for the affirmative.
AB  - Threshold strain ranges help to control the ability of modeling to increase bone
      strength and "mass" and the ability of remodeling to conserve or decrease them.
      Whether expressed as strains or stresses, the probable remodeling threshold of
      bone (MESr) lies below its modeling threshold (MESm), which lies below its
      operational microdamage threshold (MESp), which lies well below its ultimate
      strength (Fx). Given normal modeling and remodeling potentials, that arrangement
      should tend to cause whole-bone strength and stiffness to keep typical peak bone
      strains ("E") from voluntary activities from exceeding bone's modeling threshold
      and therefore from reaching its microdamage threshold. Satisfying that laddered
      "MESr < "E" < MESm << MESp <<< Fx" arrangement should minimize fatigue failures
      of bones, which might be at least one purpose of normal bone design. That
      arrangement would have practical implications that include, in part, the
      following. (A) It could make healthy young adult bones about six times stronger
      than needed for the largest voluntary loads they usually carry. (B) It suggests a
      biomechanical pathogenesis for different kinds of osteoporosis. (C) It suggests
      design criteria that load-bearing bone implants and endoprostheses should satisfy
      to endure their voluntary mechanical usage. (D) It also suggests features that
      future models of mechanical loading effects on bone strength, architecture, and
      "mass" might incorporate.

PMID- 10959618
TI  - Heated oyster shell with algal ingredient (AAACa) decreases urinary oxalate
      excretion.
AB  - In nine normal subjects, four men and five women between 23 and 49 years of age,
      800mg calcium was orally administered as active absorbable algal calcium (AAA Ca)
      (A) and calcium carbonate (CaCO3) (B), to compare with non-calcium-containing
      placebo (C) in a crossover design. Calcium, oxalate, osmolality, creatinine, and
      pH were measured in the first three morning urine samples and Ca/osmolality,
      Ca/osmolality/body weight, Ca/creatinine, and oxalate/ osmolality were calculated
      to correct for urine dilution. Ca x oxalate product was also calculated, and Ca
      oxalate crystal in the sediment was microscopically examined, semiquantitatively
      estimated as -, +, ++, or , and numerically expressed as 0, 1, 2, or 3,
      respectively. Urinary Ca excretion was similar in groups A and B, but
      significantly larger than in group C, regardless of the method of correction for
      dilution. Urinary oxalate excretion with correction for osmolality, however, was
      significantly lower in A than in B and C, which gave similar values. Urine pH was
      similar among all three groups. Ca x oxalate product was significantly higher in
      C than in A, but A and B were not significantly different. AAA Ca appeared to
      decrease urinary oxalate excretion and Ca x oxalate product more efficiently than
      CaCO3, suggesting the possibility of inhibiting the formation of Ca x oxalate
      kidney stones.

PMID- 10959619
TI  - Characteristics of regional bone mineral density and soft tissue composition in
      patients with atraumatic vertebral fractures.
AB  - To clarify the characteristics of total body and regional bone mineral density
      (BMD) and soft tissue composition in patients with atraumatic vertebral fractures
      (AVF), we measured total body and regional BMD, lean mass, and fat mass using
      dual-energy X-ray absorptiometry. Sixty-four women, aged 55-75 years, were
      divided into two groups: women with AVF (fracture group, n = 30) and women
      without AVF (nonfracture group, n = 34). Mean BMD of the second to fourth lumbar
      vertebrae (L2-4BMD), regional BMD, and soft tissue mass were measured. Regional
      BMD was measured in the head, arms, legs, ribs, thoracic vertebrae, lumbar
      vertebrae, and pelvis. Lean mass and fat mass of head, arms, legs, and trunk were
      measured. L2-4BMD, total body BMD, and BMD of the lumbar spine, thoracic spine,
      and pelvis of the fracture group were significantly lower than those of the
      nonfracture group (P < 0.001). Total lean and fat mass of the fracture group
      tended to be lower than that of the nonfracture group. The results suggest that
      BMD of weight-bearing bones, except for that of the bones of the legs of the
      fracture group, is significantly lower than that of the nonfracture group, and
      that total body lean and fat mass may be a predictor for AVF.

PMID- 10959620
TI  - A fourier transform infrared spectroscopic and solid-state NMR study of bone
      mineral in osteogenesis imperfecta.
AB  - Fourier transform infrared spectroscopy and 31P solid-state nuclear magnetic
      resonance spectroscopy were used to determine if any structural or compositional
      differences in osteogenesis imperfecta (OI) bone mineral could be detected that
      might help to explain the bone fragility observed in this disease. A previous
      study by Cassella et al. used an electron probe X-ray microanalytical technique
      to compare the calcium to phosphorus (Ca/P) molar ratios in normal bone and bone
      from patients with OI. It was demonstrated that bone from OI patients had a lower
      Ca/P molar ratio. This study demonstrated that OI bone mineral had a general
      hydroxyapatite structure and that isomorphous substitutions in the carbanoapatite
      lattice could account for the low Ca/P molar ratio.

PMID- 10959621
TI  - Meeting the evolving therapeutic needs of postmenopausal women.

PMID- 10959622
TI  - Effect of myenteric denervation on intestinal epithelium proliferation and
      migration of suckling and weanling rats.
AB  - The effects of myenteric denervation on the cell kinetics of the intestinal
      epithelium of suckling and weanling rats were investigated. The myenteric plexus
      of an ileal segment was partially ablated by serosal application of benzalkonium
      chloride (BAC) in three groups of rats: those that underwent surgery at 13 days
      and were killed 15 (13/28-day-old) or 23 (13/36-day-old) days after treatment,
      and those that were operated at 21 days (21/36-day-old) and were killed 15 days
      after treatment. The extent of denervation was assessed in whole-mount
      preparations. The cell bodies of myenteric neurones were stained by NADH
      diaphorase histochemical technique. Cell proliferation was estimated by the
      mitotic index (MI) and morphometric analysis of villus and crypt lengths using an
      image analysis system. Thickness of the muscle layers was also assessed by
      morphometry. Cell migration on the villi was estimated by the position of the
      leading labelled cell 24 h after tritiated thymidine injection. The number of
      neurones was reduced by around 80% in rats operated at 13 days, and reduced by
      98% in those operated at 21 days. The thickness of the muscle layers was
      increased in all groups of treated animals. MI was significantly higher 15 days
      after BAC-treatment in the 13/28 group. Morphological changes in the intestinal
      mucosa were observed 15 days after BAC-treatment, when there was an increase in
      villus height (13/28 group) and crypt depth (13/28 and 21/36 groups). Cell
      migration rate was accelerated in the 21/36 group. No differences where found in
      the 13/36 group. These results show the strong effect of myenteric ablation on
      cell proliferation and migration in the ileal epithelium in the first 15 days of
      treatment in suckling and in weanling rats, and the subsequent recovery of
      intestinal mucosa homeostasis later on.

PMID- 10959623
TI  - Sodium butyrate modulates cell cycle-related proteins in HT29 human colonic
      adenocarcinoma cells.
AB  - Sodium butyrate (NaB), a product of colonic fermentation of dietary fibre, has
      been shown to inhibit cell proliferation by blocking cells in the G0/G1 phase of
      the cell cycle through a mechanism of action still not completely understood. We
      investigated the effect of NaB on the level of some G1 phase-related proteins in
      a colon carcinoma cell line (HT29). In particular, we addressed our attention to
      cyclin D1 (the key regulator of G1S progression), p21waf1/cip1 (the main
      inactivator of the cyclin D/cdk complex), and p53 (the most important regulator
      of p21waf1/cip1 gene transcription). At inhibitory concentrations (higher than 1
      mM) NaB reduced cyclin D1 and p53 level in a dose-dependent manner and sustained
      the synthesis of p21waf1/cip1, probably in a p53-independent way, accounting for
      the G0/G1 block observed by flow cytometry. Present results provide further
      evidence on the molecular mechanism at the basis of the physiological role of NaB
      and support the hypothesis that an unbalanced diet, poor in carbohydrates and
      therefore in NaB, could result in functional alterations with clinical and
      carcinogenic implications.

PMID- 10959624
TI  - Heat shock-induced arrests in different cell cycle phases of rat C6-glioma cells
      are attenuated in heat shock-primed thermotolerant cells.
AB  - The response kinetics of rat C6 glioma cells to heat shock was investigated by
      means of flow cytometric DNA measurements and western blot analysis of HSP
      levels. The results showed that the effects on cell cycle progression are
      dependent on the cell cycle phase at which heat shock is applied, leading to
      either G1 or G2/M arrest in randomly proliferating cells. When synchronous
      cultures were stressed during G0 they were arrested with G1 DNA content and
      showed prolongation of S and G2 phases after release from the block. In
      proliferating cells, HSC70 and HSP68 were induced during the recovery and reached
      maximum levels just before cells were released from the cell cycle blocks.
      Hyperthermic pretreatment induced thermotolerance both in asynchronous and
      synchronous cultures as evidenced by the reduced arrest of cell cycle progression
      after the second heat shock. Thermotolerance development was independent of the
      cell cycle phase. Pre-treated cells already had high HSP levels and did not
      further increase the amount of HSP after the second treatment. However, as in
      unprimed cells, HSP reduction coincided with the release from the cell cycle
      blocks. These results imply that the cell cycle machinery can be rendered
      thermotolerant by heat shock pretreatment and supports the assumption that HSP70
      family members might be involved in thermotolerance development.

PMID- 10959625
TI  - Molecular cloning and sequence analysis of the promoter region of mouse cyclin D1
      gene: implication in phorbol ester-induced tumour promotion.
AB  - Cyclin D1 is a cell cycle regulatory protein, which acts as a growth factor
      sensor to integrate extracellular signals with the cell cycle machinery,
      particularly during G1 phase of the cell cycle. Previous study using promotion
      sensitive JB6 mouse epidermal cells, an in vitro model of the promotion stage of
      multistage carcinogenesis, showed that the expression of cyclin D1 is stimulated
      in the presence (but not in the absence) of 12-O-tetradecanoylphorbol-13-acetate
      (TPA) in these cells maintained under anchorage-independent culture conditions.
      In the present study, to explore the molecular basis of this observation, the
      promoter region of mouse cyclin D1 gene was cloned and sequenced (GenBank
      accession number AF212040). Dot matrix comparison of mouse, human and rat
      promoter sequences indicated that the mouse promoter is homologous to the human
      and more so to the rat promoters. The mouse promoter, like human and rat
      promoters, lacks canonical TATA-box or TATA-like sequence, but it has one or
      possibly two initiator (Inr) or Inr-like sequences. Energy dot plot analysis
      predicted that the mouse promoter consists of three domains: (1) the 3' domain
      contains NF-kappaB response element, cAMP-response element (CRE), Inr or Inr-like
      elements, Sp1 binding site and Oct 1 (2) the middle domain contains another Sp1
      binding site, E-box and E2F binding site and (3) the 5' domain contains TPA
      response element (TRE) and a tandem silencer element. The cyclin D1 promoter
      sequence of either promotion-sensitive or resistant JB6 mouse epidermal cells
      was, except for a few minor differences, essentially identical to the sequence
      determined for a mouse genomic clone. Since TPA is capable of stimulating the
      expression of cyclin D1 not only through TRE but also through CRE and NF-kappaB
      response element in the promoter, we tentatively propose a sequence of events
      that possibly leads to TPA-induced, anchorage-independent synthesis of cyclins D1
      and A in the promotion-sensitive JB6 mouse epidermal cells.

PMID- 10959626
TI  - Rapid fold and structure determination of the archaeal translation elongation
      factor 1beta from Methanobacterium thermoautotrophicum.
AB  - The tertiary fold of the elongation factor, aEF-1beta, from Methanobacterium
      thermoautotrophicum was determined in a high-throughput fashion using a minimal
      set of NMR experiments. NMR secondary structure prediction, deuterium exchange
      experiments and the analysis of chemical shift perturbations were combined to
      identify the protein fold as an alpha-beta sandwich typical of many RNA binding
      proteins including EF-G. Following resolution of the tertiary fold, a high
      resolution structure of aEF-1beta was determined using heteronuclear and
      homonuclear NMR experiments and a semi-automated NOESY assignment strategy.
      Analysis of the aEF-1beta structure revealed close similarity to its human
      analogue, eEF-1beta. In agreement with studies on EF-Ts and human EF-1beta, a
      functional mechanism for nucleotide exchange is proposed wherein Phe46 on an
      exposed loop acts as a lever to eject GDP from the associated elongation factor G
      protein, aEF-1alpha. aEF-1beta was also found to bind calcium in the groove
      between helix alpha2 and strand beta4. This novel feature was not observed
      previously and may serve a structural function related to protein stability or
      may play a functional role in archaeal protein translation.

PMID- 10959627
TI  - [15N,1H]/[13C,1H]-TROSY for simultaneous detection of backbone 15N-1H, aromatic
      13C-1H and side-chain 15N-1H2 correlations in large proteins.
AB  - This paper describes a [15N,1H]/[13C,1H]-TROSY experiment for the simultaneous
      acquisition of the heteronuclear chemical shift correlations of backbone amide
      15N-1H groups, side chain 15N-1H2 groups and aromatic 13C-1H groups in otherwise
      highly deuterated proteins. The 15N-1H and 13C-1H correlations are extracted from
      two subspectra of the same data set, thus preventing possible spectral overlap of
      aromatic and amide protons in the 1H dimension. The side-chain 15N-1H2 groups,
      which are suppressed in conventional [15N,1H)-TROSY, are observed with high
      sensitivity in the 15N-1H subspectrum. [15N,1H]/[13C,1H]-TROSY was used as the
      heteronuclear correlation block in a 3D [1H,1H]-NOESY-[15N,1H]/[13C,1H]-TROSY
      experiment with the membrane protein OmpA reconstituted in detergent micelles of
      molecular weight 80000 Da, which enabled the detection of numerous NOEs between
      backbone amide protons and both aromatic protons and side chain 15N-1H2 groups.

PMID- 10959628
TI  - The relative orientation of the fibronectin 6F1(1)F2 module pair: a 15N NMR
      relaxation study.
AB  - The structure of a pair of modules (6F1(1)F2), that forms part of the collagen
      binding region of fibronectin, is refined using heteronuclear relaxation data. A
      structure of the pair was previously derived from 1H-1H NOE and 3J(HalphaHN) data
      [Bocquier et al. (1999) Structure, 7, 1451-1460] and a weak module-module
      interface, comprising Leu19 and Leu28, in 6F1, and Tyr68 in 2F1, was identified.
      In this study, the definition of the average relative orientation of the two
      modules is improved using the dependence of 15N relaxation on rotational
      diffusion anisotropy. This structure refinement is based on the selection of a
      subset of structures from sets calculated with NOE and 3J(HalphaHN) data alone,
      using the quality of the fits to the relaxation data as the selection criterion.
      This simple approach is compared to a refinement strategy where 15N relaxation
      data are included in the force field as additional restraints [Tjandra et al.
      (1997) Nat. Struct. Biol., 4, 443-449].

PMID- 10959629
TI  - Backbone dynamics and solution structure refinement of the 15N-labeled human
      oncogenic protein p13MTCP1: comparison with X-ray data.
AB  - Two related oncogenes, TCL1 and MTCP1, are overexpressed in certain T-cell
      prolymphocytic leukemias as a result of chromosomal rearrangements that involve
      the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28,
      respectively. The human oncoprotein p13MTCP1 is coded by the MTCP1 gene and its
      primary sequence is highly and only homologous to that of p14TCL1, the product of
      TCL1. These two proteins likely represent the first members of a new family of
      oncogenic proteins. A previous model of the three-dimensional solution structure
      of p13MTCP1 was determined recently using exclusively homonuclear proton two
      dimensional NMR methods and, almost simultaneously, high-resolution crystal
      structures of p13MTCP1 and p14TCL1 appeared in the literature. In order to gain
      more insight into the details of the solution structure, we uniformly labeled
      p13MTCP1 with nitrogen-15. The refined structure benefits from 520 additional
      NOEs, extracted from either 15N-edited 3D experiments or homonuclear 2D NOESY
      recorded at 800 MHz, and from a nearly complete set of phi angular restraints.
      Measurements of 15N spin relaxation times and heteronuclear 15N[1H]NOEs at two
      magnetic field strengths provided additional insights into the dynamics of the
      protein backbone. On the basis of these new results, a putative binding surface
      for this particular class of oncogenes is discussed.

PMID- 10959630
TI  - Off-resonance effects in 15N T2 CPMG measurements.
AB  - The systematic difference between T2 values obtained from CPMG and T1p
      experiments was observed for backbone 15N nuclei of bacterial ribonuclease
      barnase. Theoretical consideration suggests that the observed difference is
      caused by off-resonance effects of 180 degree pulses of the CPMG pulse train.
      Namely, at off-resonance conditions T1-dependent secondary echo coherence
      pathways considerably contribute to the signal decay in the CPMG experiment and
      result in systematic (up to 10%) offset-dependent overestimation of 15N T2
      measured by the CPMG technique. Under certain circumstances off-resonance effects
      result in dependence of 15N T2 on CPMG frequency, which might be erroneously
      interpreted as conformational exchange on the millisecond time-scale. A procedure
      for numerical correction of 15N T2 (CPMG) data is proposed.

PMID- 10959631
TI  - Backbone dynamics of a bacterially expressed peptide from the receptor binding
      domain of Pseudomonas aeruginosa pilin strain PAK from heteronuclear 1H-15N NMR
      spectroscopy.
AB  - The backbone dynamics of a 15N-labeled recombinant PAK pilin peptide spanning
      residues 128-144 in the C-terminal receptor binding domain of Pseudomonas
      aeruginosa pilin protein strain PAK (Lys128-Cys-Thr-Ser-Asp-Gln-Asp-Glu-Gln-Phe
      Ile-Pro-Lys-Gly-Cys-Se r-Lys144) were probed by measurements of 15N NMR
      relaxation. This PAK(128-144) sequence is a target for the design of a synthetic
      peptide vaccine effective against multiple strains of P. aeruginosa infection.
      The 15N longitudinal (T1) and transverse (T2) relaxation rates and the steady
      state heteronuclear [1H]-15N NOE were measured at three fields (7.04, 11.74 and
      14.1 Tesla), five temperatures (5, 10, 15, 20, and 25 degrees C) and at pH 4.5
      and 7.2. Relaxation data was analyzed using both the 'model-free' formalism
      [Lipari, G. and Szabo, A. (1982) J. Am. Chem. Soc., 104, 4546-4559 and 4559-4570]
      and the reduced spectral density mapping approach [Farrow, N.A., Szabo, A.,
      Torchia, D.A. and Kay, L.E. (1995) J. Biomol. NMR, 6, 153-162]. The relaxation
      data, spectral densities and order parameters suggest that the type I and type II
      beta-turns spanning residues Asp134-Glu-Gln-Phe137 and Pro139-Lys-Gly-Cys142,
      respectively, are the most ordered and structured regions of the peptide. The
      biological implications of these results will be discussed in relation to the
      role that backbone motions play in PAK pilin peptide immunogenicity, and within
      the framework of developing a pilin peptide vaccine capable of conferring broad
      immunity across P. aeruginosa strains.

PMID- 10959632
TI  - Pressure effect on the dynamics of an isolated alpha-helix studied by 15N-1H NMR
      relaxation.
AB  - Dynamics and structure of (1-36)bacteriorhodopsin solubilized in
      chloroform/methanol mixture (1:1) were investigated by 1H-15N NMR spectroscopy
      under a hydrostatic pressure of 2000 bar. It was shown that the peptide retains
      its spatial structure at high pressure. 15N transverse and longitudinal
      relaxation times, 15N[1H] nuclear Overhauser effects, chemical shifts and the
      translation diffusion rate of the peptide at 2000 bar were compared with the
      respective data at ambient pressure [Orekhov et al. (1999) J. Biomol. NMR, 14,
      345-356]. The model free analysis of the relaxation data for the helical 9-31
      fragment revealed that the high pressure decreases the overall rotation and
      translation diffusion, as well as apparent order parameters of fast picosecond
      internal motions (S2) but has no effect on internal nanosecond motions (S2 and
      taus) of the peptide. The decrease of translation and overall rotation diffusion
      was attributed to the increase in solvent viscosity and the decrease of apparent
      order parameters S2f to a compression of hydrogen bonds. It is suggested that
      this compression causes an elongation of H-N bonds and a decrease of absolute
      values of chemical shift anisotropy (CSA). In particular, the observed decrease
      of S2f at 2000 bar can be explained by 0.001 nm increase of N-H bond lengths and
      10 ppm decrease of 15N CSA values.

PMID- 10959633
TI  - Measurement of the protein backbone dihedral angle phi based on quantification of
      remote CSA/DD interference in inter-residue 13C'(i - 1)-13Calpha(i) multiple
      quantum coherences.
AB  - A novel triple-resonance NMR method is presented for the measurement of the
      protein backbone dihedral angle phi based on differential multiple-quantum
      relaxation induced by relaxation interference between 1Halpha(i)-13Calpha(i)
      dipolar and 13C'(i - 1) (carbonyl) chemical shift anisotropy mechanisms. The
      method employs a simultaneous transfer of 15N magnetization to the inter- and
      intra-residue 13Calpha carbons as well as the directly attached carbonyl carbon
      13C'. Results obtained on 13C,15N-labeled ubiquitin demonstrate the potential of
      the method.

PMID- 10959634
TI  - Letter to the editor: 1H, 15N, 13C, and 13CO assignments and secondary structure
      determination of collagenase-3 (MMP-13) complexed with a hydroxamic acid
      inhibitor.

PMID- 10959635
TI  - Letter to the editor: sequence-specific 1H, 13C and 15N chemical shift backbone
      NMR assignment and secondary structure of the Arabidopsis thaliana PIN1At
      protein.

PMID- 10959636
TI  - Letter to the editor: assignment and secondary structure identification of the
      ribosomal protein L18 from Thermus thermophilus.

PMID- 10959637
TI  - Letter to the editor: 1H, 15N, 13C, and 13CO assignments and secondary structure
      determination of ZipA.

PMID- 10959638
TI  - Letter to the editor: 1H, 13C and 15N resonance assignments of Aquifex aeolicus
      shikimate kinase in complex with the substrate shikimate.

PMID- 10959639
TI  - Letter to the editor: 1H, 13C and 15N chemical shift assignments of the acidic
      fibroblast growth factor from Notopthalmus viridescens.

PMID- 10959640
TI  - Letter to the editor: 1H, 15N, and 13C NMR backbone assignments and secondary
      structure of the C-terminal recombinant fragment of auxilin including the J
      domain.

PMID- 10959641
TI  - Infective endocarditis: a diagnostic and therapeutic challenge for the new
      millennium.
AB  - This review on infective endocarditis (IE) is based on clinical studies carried
      out in Goteborg since 1984, data obtained from a Swedish national registry of IE
      since 1995 and existing literature. IE is still a great challenge in medicine,
      although improved bacteriological and echocardiographical techniques have
      facilitated diagnosis. In Sweden the incidence of IE is about 6 per 100,000
      inhabitants a year. During recent decades IE has changed character. Patients are
      older, fever is often the only major symptom and a new murmur is less frequent.
      Streptococci, including viridans species and staphylococci, are still the most
      common bacteria found. Antibiotic treatment for 4-6 weeks may reduce mortality of
      IE to 30-50%. For further reduction, heart surgery is necessary in 20-25% of
      patients in order to remove infected tissues and restore valve function. Rapid
      diagnosis, careful antibiotic treatment and optimal surgery may reduce mortality
      associated with treatment to 10%. Antibiotic treatment is still mainly empiric.
      Penicillin and aminoglycoside for 2 weeks only seem to be effective in
      uncomplicated IE caused by alpha-streptococci. Otherwise, 4 weeks of treatment is
      needed, but aminoglycoside treatment may be reduced to 1 week in general and 2
      weeks for enterococcal infections.

PMID- 10959642
TI  - Prevalence of HIV type 1 infection, associated clinical features and mortality
      among hospitalized children in Dar es Salaam, Tanzania.
AB  - The aim of this study was to determine the prevalence of HIV-1 infection, the
      clinical spectrum of HIV-1-associated conditions and HIV-1-associated mortality
      among children hospitalized in the medical paediatric wards at Muhimbili Medical
      Centre (MMC), Dar es Salaam, Tanzania. All children admitted to the medical
      paediatric wards of MMC between August 1995 and January 1996 were eligible for
      the study. Testing for HIV antibodies was done using 2 consecutive enzyme linked
      immunosorbent assays (ELISAs). ELISA-reactive samples from children aged 18
      months and below were further tested by a recently developed heat-denatured p24
      antigen assay. The prevalence of HIV-1 infection among the 2015 children studied
      was 19.2%. When present for 14 days or more, fever, cough, diarrhoea, ear
      discharge, oral ulcers and skin rash were all significantly more common in HIV-1
      infected than in HIV-uninfected children (p < 0.001). In the multivariate
      analysis cough, ear discharge, oropharyngeal ulcers and skin rash were found to
      be the most important symptoms. Clinical signs found to be significantly
      associated with HIV-1 infection in the univariate analysis were wasting,
      stunting, hair changes, oral thrush, oropharyngeal ulcers, lymphadenopathy, lung
      consolidation and lung crepitations (p < 0.001). In the multivariate analysis,
      oral thrush, lung crepitations, cervical lymphadenopathy, wasting and inguinal
      lymphadenopathy were found to be the most important signs. The 3 most common
      diagnoses in HIV-1-infected children were acute respiratory infection (ARI)
      (39.4%), malnutrition (38.1%) and tuberculosis (19.3%), while in HIV-uninfected
      children they were malaria (47.0%), ARI (25.0%) and malnutrition (16.1%). The
      mortality rate was 21.4% in HIV-1-infected children and 8.4% in HIV-uninfected
      children (p < 0.001). In conclusion, the prevalence of HIV-1 infection among
      hospitalized children at the main hospital in Dar es Salaam was high and
      associated with high mortality. Many symptoms and signs are indicative of HIV-1
      infection, but appropriate laboratory testing is required for diagnosis.

PMID- 10959643
TI  - Cerebrospinal fluid and plasma viral load in HIV-1-infected patients with various
      anti-retroviral treatment regimens.
AB  - Highly active anti-retroviral therapy (HAART) effectively decreases HIV-1 RNA in
      cerebrospinal fluid (CSF) and plasma in controlled clinical trials. To study the
      virological effect in CSF and plasma achieved in routine practice, HIV-1 RNA
      levels were analysed retrospectively in 27 patients on mono-nucleoside reversed
      transcriptase inhibitor (NRTI) treatment, 27 on dual-NRTI-treatment and 45 on
      HAART using a Roche Amplicor HIV-1 monitor quantitative PCR. A significant
      difference was found in the proportion of patients with a CSF viral load below 20
      copies/ml between patients treated with 1 (0%) and 2 NRTIs (41%) as well as
      between those treated with 2 NRTIs and HAART (69%). The proportion of patients
      with plasma viral load below 20 copies/ml differed significantly between patients
      on HAART (47%) and those on 2 NRTIs (0%), but not between those with 1 (0%) or 2
      NRTIs. In multivariate regression analysis, treatment regimen and prior anti
      retroviral experience (but not treatment time) were independently associated with
      the CSF viral load. Plasma viral load was independently associated with treatment
      regimen and treatment time, but not with anti-retroviral experience. Dual-NRTI
      treatment affects the CSF viral load substantially, while HAART is required to
      achieve an essential decline in plasma viral load.

PMID- 10959644
TI  - Prognostic value of single measurements of beta-2-microglobulin, immunoglobulin A
      in HIV disease after controlling for CD4 lymphocyte counts and plasma HIV RNA
      levels.
AB  - The interrelationships between the CD4 lymphocyte count, plasma viral load [human
      immunodeficiency virus (HIV) RNA], beta-2-microglobulin (beta2-M) and
      immunoglobulin A (IgA) and the mortality risk was explored in 234 HIV-infected
      individuals (median CD4 count 230 cells/mm3, range 1-1,247). Product-moment
      correlation analysis was used to study the association between beta2-M, IgA and
      HIV RNA. A proportional hazards Cox model was used to estimate the relative
      hazard (RH) of death. Both beta2-M (r = 0.49, p < 0.0001) and IgA (r = 0.42, p <
      0.0001) were positively correlated with HIV RNA. High beta2-M levels were
      associated with an increased risk of death in both univariate Cox analysis and
      after adjustment for HIV RNA, CD4 lymphocyte count and age [RH = 1.16 per 100
      nmol/l higher beta2-M, 95% confidence interval (CI) 1.05-1.27]. Raised IgA levels
      were associated with shorter survival in individuals with a CD4 count above 50
      cells/mm3 in univariate analysis as well as after adjusting for age and CD4
      lymphocyte count (RH = 1.19 per 10 micromol/l higher IgA, 95% CI 1.01-1.39).
      However, this association was no longer significant after further adjusting for
      HIV RNA. In conclusion, beta2-M levels provided additional prognostic information
      for survival to the information obtained by CD4 count and HIV RNA levels, whereas
      serum IgA only was a weak prognostic marker in this fairly progressed cohort.

PMID- 10959645
TI  - Beta-haemolytic streptococci isolated from acute sore-throat patients: cause or
      coincidence? A case-control study in general practice.
AB  - As beta-haemolytic streptococci can be cultured in people with and in those
      without a sore throat, a case-control study was set up in 43 family practices in
      The Netherlands. The association was tested between the number of colony counts,
      specific T/M types and exotoxin genes and an acute sore throat. Duplicate throat
      swabs were taken from 663 sore-throat patients, selected by clinical criteria,
      and from 694 healthy controls. They were cultured for beta-haemolytic
      streptococci by combining several updated laboratory methods. Approximately 40%
      of the controls and 80% of the patients had beta-haemolytic streptococci-positive
      cultures. When focusing on cultures with high colony counts, not only group A
      (46%), but also non-group A streptococci (20%), predominated significantly in
      adult patients compared with controls. No T/M or exotoxin gene type was
      significantly more prevalent in patients than in controls. Thus, semiquantitative
      analysis, but not T/M and exotoxin gene typing, showed an association between
      beta-haemolytic streptococci and active disease. Groups A, C and G streptococci
      were found to be potentially pathogenic in adult sore-throat patients, and should
      be included in the discussion on the use of rapid antigen detection tests and
      penicillin treatment in primary care.

PMID- 10959646
TI  - Escherichia coli 'O' group serology of a haemolytic uraemic syndrome (HUS)
      epidemic.
AB  - This is the first comprehensive serological analysis of a haemolytic uraemic
      syndrome (HUS) outbreak. A wide range of 'O' group Escherichia coli antibody
      responses in patients and controls was examined. The study provides a unique
      insight into the epidemiology of such epidemics, points a way to the most
      appropriate investigation of these and indicates possible answers to a number of
      issues related to severity of disease. In order to be able to test for a wide
      variety of E. coli 'O' antigens, a microagglutination assay was used to examine
      E. coli 'O' group serological responses of 22 children admitted to hospital with
      HUS and 14 contemporaneous age-matched controls. A total of 51 'O' serogroup
      strains were used. These included 'O' groups reported to be associated with cases
      of HUS, with 6 isolates from patients associated with the Adelaide outbreak (O26,
      O111, O123 and O157), environmental Verocytotoxigenic/Shiga-toxin producing
      Escherichia coli (VTEC/STEC) strains and common human commensal strains. Sixteen
      clinically confirmed HUS cases (72.7%) of 22 seroconverted to 1 or more
      serogroups of which 11 (50%) seroconverted to O111 (the serogroup isolated from
      16 patients). In addition, 11 (50%) and 10 (45.5%) developed antibody to O137 and
      O145, respectively, although no stool isolates of these serogroups were made.
      Seventeen (77.3%) of 22 HUS patients had antibody to serogroup O157, with 11
      (50%) seroconversions, however, O157:H- was isolated from only 2 of these.
      Overall, titres ranged from 100 to 6400, some of the highest in 3 patients were
      against O157, whose faeces yielded only Enterohaemorrhagic E. coli (EHEC) O111,
      and only 1 developed O111 antibody. Mixed infection was demonstrated
      serologically by microagglutination (confirmed by Western blot) and was
      consistent with the findings of multiple serogroups of VTEC found in the
      mettwurst incriminated as the source, and suggests further strains (not found in
      the source or in patients' faeces) were probably also involved. In HUS associated
      with EHEC infection, multiple strain infection may be the rule rather than the
      exception. A relationship with clinical severity deserves further investigation.
      Non-O157 EHEC (in addition to O157) should be sought in all future outbreaks of
      EHEC disease.

PMID- 10959647
TI  - Chemical cleavage of mismatches in heteroduplexes of the rpoB gene for detection
      of mutations associated with resistance of Mycobacterium tuberculosis to
      rifampin.
AB  - In order to detect mutations in the core region of the RNA polymerase B (rpoB)
      subunit gene of Mycobacterium tuberculosis that are known to be associated with
      resistance to rifampin, we applied rapid chemical cleavage of mismatches (CCM) to
      heteroduplexes formed between the DNA of M. tuberculosis H37Rv and strains
      resistant to rifampin. DNA fragments amplified from normal and mutant rpoB genes
      by polymerase chain reaction were mixed, denatured and re-annealed to create
      heteroduplexes containing mispaired bases reactive to modification by
      hydroxylamine (cytosine mismatches) or osmium tetroxide (thymine mismatches) and
      cleavage of DNA by piperidine at the position of modified base. The cleaved
      products and the heteroduplexes were separated by polyacrylamide-urea gel
      electrophoresis and detected by autoradiography. The position of mutations was
      confirmed by DNA sequencing of the amplified DNA fragments. The results suggest
      further applicability of the CCM method as a means to screen M. tuberculosis
      isolates for mutations associated with drug resistance.

PMID- 10959648
TI  - Serum C-reactive protein cannot differentiate bacterial and viral aetiology of
      community-acquired pneumonia in children in primary healthcare settings.
AB  - Whether serum C-reactive protein (CRP) can be used to distinguish bacterial from
      viral pneumonia was studied in 193 paediatric patients who were identified in a
      prospective, population-based study. The proportion of patients < 5 y of age was
      51%, 53% of these and 12% of the older patients were treated in hospital.
      Pneumococcal aetiology of infection was studied in paired sera by antibody and
      immune-complex assays, and chlamydial, mycoplasmal and viral aetiologies by
      routine antibody assays. CRP concentration was measured by immunoturbidometry.
      Pneumococcal infection (mixed infections with other agents included) was present
      in 57 cases, mycoplasmal and/or chlamydial infection (pneumococcal infections
      excluded) in 43, and viral infection (pneumococcal, mycoplasmal and chlamydial
      infections excluded) in 29 cases. The mean CRP concentrations (95% confidence
      interval) in these groups were 26.8 mg/l (20.1-33.5 mg/l), 31.8 mg/l (20.5-33.1
      mg/l) and 26.1 mg/l (19.1-33.1 mg/l), respectively, and 24.9 mg/l (18.8-31.0
      mg/l) in patients with no aetiological findings. When CRP values were compared
      between the 2 diagnostic groups of pneumococcal infections (antibody and immune
      complex positive) no difference was found. In infants < 12 months of age the mean
      CRP concentration was 14.6 mg/l, and in 11 (65%) of them it was unmeasurable (<
      10 mg/l). No significant differences were seen between hospitalized patients and
      outpatients. In conclusion, CRP concentration had no significant association with
      the microbial aetiology of pneumonia.

PMID- 10959649
TI  - Comparison of the effects of hospitalization and antibiotic usage on the aerobic
      intestinal flora.
AB  - Antimicrobial resistance among bacteria has arisen ever since antimicrobial
      agents were introduced in the clinic. Unfortunately, it seems that resistance is
      now emerging at a more rapid rate than ever before, as a consequence of the
      widespread use of antimicrobial agents. The spread of these multiresistant
      microorganisms is an increasing threat in many countries. The human intestinal
      flora is a huge potential reservoir of resistant microorganisms. Antimicrobial
      resistance in clinical isolates may cause serious infections and treatment
      failure, and lead to the use of higher doses or more toxic alternative drugs.
      This study was planned so as to compare the effects of hospitalization and
      antibiotic usage on the aerobic intestinal flora and included 43 hospitalized
      adult patients without any previous history of hospitalization and antibiotic
      usage during the last 30 d. Patients were divided according to their
      antimicrobial therapy, into treated and untreated groups. The individual use of
      antimicrobials was recorded. Antibiotic usage was found to be more effective on
      the aerobic intestinal flora compared with hospitalization without such
      medication.

PMID- 10959650
TI  - Risk and case fatality rate of meningitis in patients with liver cirrhosis.
AB  - Bacterial infections are major causes of morbidity and death in patients with
      liver cirrhosis. The risk of bacterial meningitis in these patients is unknown,
      however. In this study on a nation-wide cohort of 22,743 patients with liver
      cirrhosis in Denmark an incidence rate of bacterial meningitis of 54.4 per
      100,000 was found [95% confidence interval (CI) 40.3-71.9]. The highest incidence
      rate was found in patients with alcoholic cirrhosis, 65.3 per 100,000 person
      years (95% CI 46.2-89.6), compared with 34.6 per 100,000 person-years (95% CI
      17.3-61.9) in patients with non-alcoholic cirrhosis. The 30-d case fatality rate
      was 53.1% (95% CI 38.3-67.5), and high age and alcoholic cirrhosis were
      associated with the highest case fatality rates. The main bacterial pathogens
      were pneumococci and unspecified bacteria. These findings suggest that patients
      with liver cirrhosis are at increased risk of bacterial meningitis with a poor
      prognosis.

PMID- 10959651
TI  - Epidemiology of vascular catheter-related bloodstream infections in a large
      university hospital in Israel.
AB  - Intravascular catheter-related infection and associated bacteraemia constitute a
      serious and increasing problem among nosocomial infections. As a part of an
      ongoing survey of positive blood cultures, all catheter-related bloodstream
      infections (CR-BSI) were reviewed in the authors' Medical Center in 1996, in
      order to evaluate the magnitude and seriousness of this problem. The largest
      group (28%) of hospital-acquired bacteraemia by 1 source of infection during 1996
      was CR-BSI, identified in 110 patients with 126 episodes. The vascular line was
      central in 83 (66%), peripheral in 24 (19%), tunnelled in 18 (14%) and arterial
      in 1 (1%). Among the 83 central CR-BSI no sign of local inflammation was detected
      in 65%. Gram-positive and gram-negative bacteria shared equal parts among the 145
      blood isolates; Staphylococcus aureus was the most common species (43/145, 30%)
      followed by Klebsiella pneumoniae (15/145, 10%); 11 (8%) isolates were Candida
      species. Fungal isolates were more common among tunnelled catheter infections
      than among others (6/18, 33% vs. 5/108, 5%, p < 0.001). Crude mortality was 35%
      (38/110), while attributable mortality was 14% (15/110), mostly associated with
      central line infection. Catheter-associated bacteraemias cause significant
      morbidity and mortality, and have become the most common source of hospital
      acquired bacteraemia. There is a need to implement more effective infection
      control measures and more advanced technologies in an effort to reduce this
      unacceptably high incidence.

PMID- 10959652
TI  - Hospital-treated infectious diseases in Western Pomeranian region in a 5-year
      surveillance: importance for travellers.
AB  - Retrospective analysis of the incidence of infectious diseases in the five-year
      period 1994-1998 as recorded by the Department of Infectious Diseases of the
      Pomeranian Medical School, has been presented. In this period contagious diseases
      were diagnosed in 3,863 adults with mean age of 42.8 +/- 33.5 y. Most patients
      still had viral liver diseases, but we observe some major changes in the
      epidemiology of infectious diseases in our region. There is an increased number
      of hospitalisations due to chronic hepatitis and liver cirrhosis as well as due
      to symptomatic HIV infections, whereas some acute diseases namely acute hepatitis
      B and infectious intoxication show decreasing tendency.

PMID- 10959653
TI  - Pronounced monocytosis in a case of nephropathia epidemica.
AB  - Nephropathia epidemica is a mild form of haemorrhagic fever with renal syndrome.
      Thrombocytopenia is common and characteristic. We report here a case of a young
      man with nephropathia epidemica and marked transient monocytosis.

PMID- 10959654
TI  - Acute phlegmonous jejunitis and viridans streptococcal peritonitis associated
      with bronchial carcinoma.
AB  - A 61-y-old man developed acute non-specific phlegmonous jejunitis associated with
      relatively mild diffuse peritonitis. Bacteriological cultures of the abundant
      peritoneal fluid resulted in only growth of viridans streptococci (Streptococcus
      mitis and S. salivarius). Antibiotic treatment had a favourable effect, but a
      hitherto unknown bronchial cancer led to his death 5 months later. It is assumed
      that this peculiar case was the result of the immunosuppressive effect related to
      the malignant neoplasm (opportunistic infection).

PMID- 10959655
TI  - Community-acquired methicillin-resistant Staphylococcus aureus brain abscess in
      an immunocompetent individual.
AB  - A 52-y-old woman with a community-acquired methicillin-resistant Staphylococcus
      aureus brain abscess who was successfully treated with surgical drainage and
      antibiotics is described. The increase in community-acquired methicillin
      resistant S. aureus and the impact this will have on empirical treatment of such
      infections are discussed.

PMID- 10959656
TI  - Difficulties in diagnosing Brucella spondylitis.
AB  - We describe a case of culture-proven Brucella spondylitis in a 28-y-old Turkish
      male asylum seeker who had arrived to Norway 6 months earlier. Several diagnostic
      difficulties, including rapid in vitro growth and misidentification of the
      causative microorganism in biochemical gallery strip tests, resulted in late
      diagnosis.

PMID- 10959657
TI  - Endocarditis caused by Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia is frequently isolated from hospital environments.
      In recent years, it has been reported that this bacterium is causing hospital
      infections at increasing rates and is gaining importance because of its multiple
      resistance. Although it has been related to several infections, endocarditis
      caused by S. maltophilia is rarely encountered. In this case study, endocarditis
      in a 40-y-old man with a history of aortic valve replacement is presented. Blood
      cultures revealed S. maltophilia to be the aetiological agent, which showed
      multiresistance to various antibiotics. Ticarcillin-clavulanate and trimethoprim
      sulfamethoxazole were used in the treatment.

PMID- 10959658
TI  - Primary costochondritis due to Escherichia coli.
AB  - We present a case of primary costochondritis by Escherichia coli, in a diabetic
      woman. The patient suffered a urinary infection by E. coli which may have been
      the source of haematogenous spread. She received medical and surgical therapy and
      5 months later, she was asymptomatic.

PMID- 10959659
TI  - Salmonella virchow meningitis in an adult.
AB  - We report here a case of meningitis caused by Salmonella virchow in a woman
      without signs or history of immunosuppression. Salmonella meningitis is a rare
      complication of human salmonellosis. The patient was successfully treated with
      ciprofloxacin. To our knowledge, this is the first reported case of confirmed
      meningitis in an adult caused by this serotype.

PMID- 10959660
TI  - Cutaneous tuberculosis.
AB  - Tuberculosis continues to be a significant health problem in developing
      countries. Although cutaneous tuberculosis is uncommon, disseminating skin
      involvement may still be seen, especially patients from rural areas. A case is
      reported of disseminated tuberculosis presenting with different clinical forms of
      cutaneous lesions, pulmonary and liver involvement in an immunocompetent patient.

PMID- 10959661
TI  - Drug-resistant tuberculous mastoiditis in 2 children.
AB  - Tuberculosis of the middle ear and mastoid is uncommon nowadays. Two cases of
      drug-resistant tuberculous mastoiditis in immunocompetent Greek native children
      are reported and the diagnostic and therapeutic difficulties of this rare
      condition are discussed.

PMID- 10959662
TI  - Pneumonia due to Scedosporium apiospermum in a patient with HIV infection.
AB  - A 29-y-old woman from Congo Democratic Republic was admitted to hospital with
      dyspnoea of 5-months duration. Chest X-ray showed left white lung and infiltrates
      of the right superior lobe. The patient underwent left pneumonectomy.
      Histopathological examination showed pulmonary cavitary lesions and bronchectasis
      full of branching septated fungi. Cultures yielded Scedosperium apiospermum.

PMID- 10959663
TI  - Coccidioidomycosis as imported atypical pneumonia in Sweden.
AB  - Coccidioidomycosis, an endemic fungal infection of the western hemisphere causes
      serious disease in immunocompromised individuals. In immunocompetent patients, a
      moderate flu-like disease may develop. We report here an imported Scandinavian
      case of a culture-proven coccidioidomycosis, initially presenting as an atypical
      pneumonia. Pleuritic symptoms, positive epidemiology and eosinophilia led to
      suspicion of the diagnosis, which was further supported by serology.

PMID- 10959664
TI  - Acremonium strictum fungaemia in a paediatric patient with acute leukaemia.
AB  - A 7-y-old boy with relapsed acute lymphatic leukaemia developed fungaemia due to
      Acremonium strictum, a fungus belonging to the group of the hyaline hyphomycetes.
      Initially, the fungus was misdiagnosed as Candida sp. due to the presence of
      abundant adventitious forms. At the time of diagnosis the patient was neutropenic
      and had a central venous catheter (CVC) in situ. The formation of an occlusive
      thrombotic mass in the v. subclavia dextra complicated the infection. Treatment
      consisted of amphotericin B, fluconazole, granulocyte colony-stimulating factor
      (G-CSF) and removal of the CVC. However the patient responded clinically only
      after the intravascular thrombus had been removed surgically. Amphotericin B,
      voriconazole and terbinafine showed high activity in vitro against the Acremonium
      isolate. A literature review revealed 5 other immunocompromised paediatric
      patients with a systemic or localized infection due to Acremonium spp.

PMID- 10959665
TI  - Changing profile of HIV-1 serotypes in Iceland during 1989-96.
AB  - A total of 63 HIV-1 strains collected in Iceland during the years 1989-96 were
      typed into serotypes A-E using a peptide-based enzyme immunoassay. The majority
      of the strains were of serotype B (66.6%). 22.2% were untypeable by this method.
      Until 1993 only serotype B was found, but in 1993 and after that date other
      serotypes, especially E (7.9%) were detected, indicating the spread of serotypes
      previously confined to developing countries. This may reflect the increase in the
      number of Icelanders travelling to distant countries and the increased
      immigration into Iceland from developing countries.

PMID- 10959666
TI  - Role of TTV in acute non-A-E hepatitis in Turkey.

PMID- 10959667
TI  - The epidemiology of nephropathia epidemica in Finland: clinical diagnosis vs.
      serological diagnosis.

PMID- 10959668
TI  - Influenza immunization and indinavir pharmacokinetics.

PMID- 10959669
TI  - Mycobacterium shimoidei, an easily misdiagnosed non-tuberculous pulmonary
      mycobacterium.

PMID- 10959670
TI  - A comment on recent teaching of human anatomy in the United States.

PMID- 10959671
TI  - Tendinous arch of the pelvic fascia: application to the technique of paravaginal
      colposuspension.
AB  - The authors give a description of the anatomy and topography of the tendinous
      arch of the pelvic fascia (TAPF), in order to facilitate its location during
      surgery. 35 TAPF in 25 female cadavers were dissected. The reproducibility of the
      landmarks was then verified at laparotomy. The TAPF can be easily identified and
      its resistance remains constant, even when the pelvic floor is hypotrophic. Its
      anterior extremity (d2) is at about 46 mm on a line perpendicular to the anterior
      edge of the pectineal ligament (35-55 mm), next to the pubovesical ligament. Its
      median part (dl) is perpendicular to the obturator foramen at a site located at
      an average of 30 mm below the obturator foramen (25-50 mm). Its posterior end is
      located at the ischial spine. These anterior landmarks, the only ones useful
      during surgery, allow its very easy location with the palmar surface of the
      finger. Testard and Delancey demonstrated the major role of the TAPF in
      stabilising the urethra submitted to strain. Richardson described a technique of
      paravaginal suspension for curing paravaginal fascial defect. The TAPF has never
      been well described, but his work allows its easy location during surgery. The
      suture of the vagina to the TAPF allows a more physiologic and stronger
      suspension of the bladder neck than other classical techniques.

PMID- 10959672
TI  - Radiologic anatomy of the spinal dorsal horn at the cervical level (anatomic-MRI
      correlations).
AB  - The spinal dorsal horn is known for its important functional role in the field of
      transmission and modulation of sensory afferents. Because of this, the dorsal
      horn represents a target for numerous analgesic and antispastic procedures. Thus,
      it would be interesting to develop imaging dedicated to this spinal structure.
      The purpose of this study was to investigate the radiologic anatomy of the
      cervical dorsal horn by magnetic resonance imaging (MRI) (1.5T). The first step
      consisted in the validation of the anatomic information provided by MRI on 5
      human cadavers. A spin-echo sequence (T2, 2000/45) enabled the demonstration of
      good correlations between histologic sections and axial MRI slices performed at
      the corresponding cervical levels. The second step was the <<in vivo>>
      exploration of 20 subjects, aiming at the development of a gradient echo sequence
      (T2*) with a conventional MRI unit, compatible with a routine clinical
      examination. The dorsal horn was clearly identified in 77% of the axial slices
      performed (n = 300). The angle between the dorsal horn axis and the sagittal
      plane was measured as from 25.5 degrees at C2 to 40 degrees at C8 segments. The
      results of this anatomico-radiologic study of the cervical dorsal horn suggest
      that preoperative MRI could be useful to design the surgical approach to this
      structure, as performed during cervical microsurgical drezotomy (DREZ = dorsal
      root entry zone) for the treatment of selected cases of chronic pain or disabling
      spasticity in the upper limbs.

PMID- 10959673
TI  - An investigation of the conus medullaris and filum terminale variations in human
      fetuses.
AB  - The morphologic structure of the conus medullaris and filum terminale was
      investigated by dissection in 123 human fetuses, obtained from Selcuk University,
      Faculty of Medicine and Maternity hospital of Konya between 1992-1995. In 78
      fetuses, the conus medullaris and filum terminale had a normal morphologic
      aspect, whereas there was a slight depression or groove formation in the closure
      region of the caudal neuropore in 45 fetuses. In 15 fetuses, important
      malformations of the cranium and vertebral column were observed. The morphologic
      aspects of the conus medullaris in 30 fetuses were abnormal in shape and
      position, among them 24 fetuses had an abnormal filum terminale (grooved,
      depressed, thickened or duplicated) whereas it was normal in 6. Deficiency of
      closure of the caudal neuropore was considered to have a negative effect on the
      fetal development of the filum terminale.

PMID- 10959674
TI  - Arterial vascularisation of the atrioventricular node.
AB  - The aim of this study was to define the anatomic characteristics of the principal
      arterial source of the atrioventricular node, known as the artery of the
      atrioventricular node. Forty hearts were studied by various anatomic and
      radiologic methods: dissection, injection-dissection, injection-corrosion and
      injection-radiography, but only 23 results were interpretable. The right coronary
      artery represented the commonest arterial source of the atrioventricular node
      (21/23 hearts) but numerous variations in the origin and topography of the nodal
      artery were found.

PMID- 10959675
TI  - Formation and location of the sural nerve in the newborn.
AB  - In this study, the location and formation of the sural nerve were examined in 40
      legs of new-born cadavers. The sural nerve was formed by the peroneal
      communicating branch from the common peroneal nerve joining the medial sural
      cutaneous nerve in 27 of 40 legs (67.5%). It was formed by the peroneal
      communicating branch from the lateral sural cutaneous nerve joining the medial
      sural cutaneous nerve in 4 (10%). It was formed by the peroneal communicating
      branch from the common peroneal nerve and fibers from the posterior femoral
      cutaneous nerve joining the medial sural cutaneous nerve in 2 (5%). In 5 of 40
      legs (12.5%), the medial sural cutaneous nerve was in the place of the sural
      nerve without joining any other nerve. In one case (5%), the sural nerve was not
      formed bilaterally.

PMID- 10959676
TI  - Can the human intervertebral disc be compared to a diarthrodial joint?
AB  - The joint between human vertebral bodies is traditionally classified as a
      symphysis, a major cartilaginous synarthrosis. However, it has been suggested by
      some authors to compare the intervertebral disc (IVD) to a diarthrodial joint.
      The bases of this comparison are reviewed and discussed. In his description of
      1895, Luschka saw the IVD as a diarthrodial joint containing articular cartilages
      and synovium in the annulus fibrosus. Subsequently, histologic and
      ultrastructural investigations into the cells and extracellular matrix of the
      nucleus pulposus (NP) supported the same hypothesis. More recently, the
      appearances of the IVD in magnetic resonance imaging (MRI) and discography, as
      well as clinical considerations were interpreted in the same way to simplify
      understanding of IVD pathology. However, a number of objections involving
      general, morphological, embryological, biochemical, histologic, radiological and
      clinical considerations demonstrate the limitations of this hypothesis. The
      general structural and mechanical principles of joint classification are
      mentioned to highlight the basic differences between the IVD and a synovial
      joint. An overview of the development of these joints, and a review of the
      literature dealing with ultrastructural aspects of the NP, with histopathological
      studies of the IVD, and with the normal appearance of the IVD on MRI and its age
      related changes has led us to refute the hypothesis of this analogy. The IVD
      cannot be compared to a synovial joint, explaining why most of its pathologic
      features are quite different from those of a joint of the appendicular skeleton.

PMID- 10959677
TI  - Review and evaluation of anatomy sites on the Internet (updated 1999).
AB  - In a preceding study, we had reviewed and evaluated the anatomy sites available
      on the Internet. The evolution of the available sites, the disappearance of
      certain sites and the appearance of new sites led us to update this list. In
      addition, the German-speaking sites were included in the study, which previously
      included only the Anglophone and French-speaking sites. Forty-eight sites were
      indexed and their addresses are available on the site of the Laboratory of
      Anatomy of the Faculty of Medicine Lyon-Nord (http://rockefeller.univ
      lyon1.fr/Anatomie-Lyon- Nord). Compared to the scores allotted in 1998, we noted
      in 1999 a significant increase (p = 0.03) in the total score (12.13 +/- 2.98 vs.
      11.23 +/- 2.28/20), which shows that the quality of the anatomic sites available
      on the Internet has improved.

PMID- 10959678
TI  - The subclavius posticus muscle: a factor in arterial, venous or brachial plexus
      compression?
AB  - During dissection practice in 1993 and 1995 to 1999, we found an aberrant muscle
      which connected the first costal cartilage and the superior margin of the scapula
      in 12 sides (4.8%) of 11 cadavers (8.9%) among 248 sides of 124 cadavers. The
      muscle originated from the cranial surface of the sternal end of the first rib,
      ran laterodorsally, and inserted into the superior margin of the scapula.
      According to the origin and insertion, the aberrant muscle was considered to be
      the subclavius posticus (Rosenmuller, 1800). We also examined the supraclavicular
      region of a living subject by MR imaging to estimate the course of such an
      aberrant muscle. It is thought that the aberrant muscle runs on the anterior
      surface of the subclavian vein and crosses over the brachial plexus. Such a
      muscle could be considered as a possible factor causing the Paget-von Schrotter
      syndrome which is recognized as spontaneous or effort-related thrombosis of the
      axillo-subclavian vein. It is recommended to take into account the possible
      existence of such an aberrant muscle during the examination of patients with
      thoracic outlet syndrome, especially in those with symptoms of venous
      compression.

PMID- 10959679
TI  - Unusual origin of the right renal artery: a case report.
AB  - An anomalous origin of the right renal artery was observed in a 50-year-old male
      cadaver. The importance of this variation of the right renal artery and superior
      mesenteric artery arising from a common trunk is emphasised.

PMID- 10959680
TI  - Bilateral anomaly of anterior bellies of digastric muscles.
AB  - During dissection of the submental region, the anterior bellies of the right and
      left digastric muscles were found to have two separate portions, inserting into
      different locations in the submental region. The lateral portions of the anterior
      bellies of the digastric muscles originated from the digastric fossa and inserted
      into the hyoid bone. The medial parts of the anterior bellies of the right and
      left digastric muscles ran medially and inserted into the mylohyoid raphe on both
      sides, forming accessory digastric muscles. This anatomic abnormality of the
      muscle could be significant in surgical procedures involving the submental
      region.

PMID- 10959681
TI  - Total anomalous arterial supply to the liver and gallbladder from the
      gastroduodenal artery: a case report.
AB  - Anomalous arteries to the liver are not uncommon and usually arise from the
      superior mesenteric artery, the left gastric artery or directly from the aorta.
      We report a case of total replacement of the arteries to the right and left liver
      by separate right and left hepatic arteries arising from the gastroduodenal
      artery. The proper hepatic artery was absent. The gallbladder was supplied from
      the anomalous right hepatic artery.

PMID- 10959682
TI  - Developing basic and clinical research on von Willebrand factor and von
      Willebrand disease.

PMID- 10959683
TI  - Identification of eight novel single-nucleotide polymorphisms at human tissue
      type plasminogen activator (t-PA) locus: association with vascular t-PA release
      in vivo.
AB  - Recently, we reported that an Alu insertion polymorphism of the tissue-type
      plasminogen activator (t-PA) gene is associated with vascular t-PA release rates
      in man. In the current study we searched the t-PA gene for putative functional
      genetic variants in linkage disequilibrium (LD) with this polymorphism. Healthy
      individuals with different Alu genotypes and contrasting t-PA release rates were
      studied. Regulatory and coding regions of the t-PA gene were sequenced. Eight
      single-nucleotide polymorphisms (SNPs) were identified. Three of these were in
      significant LD with the Alu polymorphism and consequently associated with t-PA
      release rates; one in the far upstream enhancer, one in exon 6, and one in intron
      10. The enhancer SNP resides within a GC box. Electrophoretic mobility shift
      assay (EMSA) revealed a reduced binding affinity of Sp1 to the T allele, which is
      the allele associated with a low t-PA release rate. Variations in exon 6 and
      intron 10 were silent and without apparent effect on splicing, respectively.

PMID- 10959684
TI  - Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and
      subsegmental pulmonary embolism. A comparison with pulmonary angiography.
AB  - STUDY OBJECTIVE: To assess the accuracy of a rapid ELISA D-dimer assay for the
      exclusion of pulmonary embolism (PE) in patients suspected of PE, using pulmonary
      angiography alone as reference method rather than a diagnostic strategy including
      lung scintigraphy and leg vein ultrasonography. METHODS: In 342 patients who were
      examined by pulmonary angiography to diagnose or exclude PE, the accuracy of the
      quantitative rapid VIDAS D-dimer test for the exclusion of PE was evaluated
      retrospectively. D-dimer levels were assayed in frozen samples collected during
      the diagnostic work-up at the time of pulmonary angiography while on treatment
      with unfractionated heparin for 1-2 days. RESULTS: Mean plasma D-dimer
      concentrations were increased in patients with angiographic evidence of PE (P
      <0.0001). The sensitivity of D-dimer for segmental PE was 98%, its accuracy in
      excluding segmental PE was 99%, higher than the respective figures for
      subsegmental PE (76% and 94%; P <0.01, both). For both forms of PE combined the
      sensitivity was 90% and the negative predictive value 94%. DISCUSSION: The
      sensitivity and negative predictive values reported here, are low compared with
      previous studies using the same rapid ELISA D-dimer assay. This probably reflects
      an overlooking of mild cases of subsegmental PE in previous studies, although a
      reduction of D-dimer levels by the heparin pretreatment may have contributed to
      part of the discrepancy. Prospective studies are needed to clarify this issue.

PMID- 10959685
TI  - Impact, diagnosis and treatment of von Willebrand disease.

PMID- 10959686
TI  - Acquired von Willebrand syndrome: from pathophysiology to management.

PMID- 10959687
TI  - Persistently elevated levels of von Willebrand factor antigen in HIV infection.
      Downregulation during highly active antiretroviral therapy.
AB  - Levels of circulating von Willebrand factor (vWf) antigen are thought to reflect
      endothelial involvement in various disorders. In the present study we found
      markedly elevated plasma levels of vWf in HIV-infected patients demonstrated on
      both cross-sectional and longitudinal testing. Notably, we found that a
      persistent rise in vWf antigen was associated with progression of HIV-related
      disease. This elevation of vWf antigen represented functionally normal vWf as
      evaluated by plasma FVIII, ristocetin cofactor assay and vWf multimer analyses.
      While HIV-infected patients showed enhanced platelet activation, platelets did
      not contribute substantially to the increased vWf levels. The high vWf levels
      were significantly correlated with high viral load, and during HAART, the
      pronounced decline in HIV RNA levels was accompanied by a corresponding decrease
      in vWf. The persistent elevation of functionally normal vWf during HIV infection,
      most probably reflecting a persistent endothelial cell activation, may have an
      important role in the pathogenesis of HIV infection.

PMID- 10959688
TI  - Type 2M vWD resulting from a lysine deletion within a four lysine residue repeat
      in the A1 loop of von Willebrand factor.
AB  - Type 1 von Willebrand disease is characterized by a decreased plasma
      concentration of functionally normal von Willebrand factor (vWF) whereas type 2M
      is characterised by an abnormal vWF displaying decreased affinity for platelets.
      In these two types of patients, the multimeric structure of vWF is normal. We
      report here the identification, in two unrelated families from the UK and
      Algeria, of an in-frame 3 bp deletion, at the heterozygous state, resulting in
      the deletion of a lysine residue within a four lysine repeat at position 642-645
      of the mature vWF subunit (del K 1405-1408 in pre-pro vWF). The patients who have
      a discrepancy between vWF antigen level and vWF ristocetin cofactor activity
      exhibited decreased ristocetin-induced binding but only a slight decrease in the
      percentage of high molecular weight (HMW) multimers in plasma. Recombinant vWF
      harbouring this deletion did not bind to platelet GPIb in the presence of
      ristocetin or botrocetin although the protein is multimerized. Consequently, this
      lysine deletion was considered as a type 2M vWD mutation.

PMID- 10959689
TI  - Local and systemic effects of intra-arterial desmopressin in healthy volunteers
      and patients with type 3 von Willebrand disease. Role of interleukin-6.
AB  - Intra-arterial desmopressin caused dose and time dependent increases (p <0.001
      for all) in forearm blood flow (all doses) and plasma tissue plasminogen
      activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma
      t-PA concentrations rose in both forearms, there was a modest local release of t
      PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin
      doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C
      concentrations rose in both forearms (p <0.001) and correlated with the rise in
      interleukin-6 concentrations (r = 0.92, p <0.001: r = 0.85, p = 0.002
      respectively). Neither desmopressin nor substance P caused t-PA, vWf or Factor
      VIII:C release in the patients, although desmopressin increased plasma
      interleukin-6 concentrations as in healthy volunteers. We conclude that
      desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic
      mechanisms, possibly mediated by cytokine release. Patients with type 3 vWD
      appear to have a generalised failure to release t-PA acutely despite a normal
      interleukin-6 response to desmopressin infusion.

PMID- 10959690
TI  - Plasma concentration of von Willebrand factor in acute myocardial infarction.
AB  - Recent investigations have revealed the crucial role of von Willebrand factor
      (vWF) in platelet thrombus formation under flow conditions. The plasma
      concentrations of vWF were measured together with various hemodynamic and
      hemostatic parameters in 51 cases of acute myocardial infarction. In 10 randomly
      selected cases, the plasma concentrations and distribution of multimers vWF were
      serially determined after reperfusion therapy by percutaneous transluminal
      coronary angioplasty (PTCA). The vWF concentration at the onset of the acute
      myocardial infarction was significantly higher than in an age-matched control
      group (vWF AG: 18.7 +/- 1.2 microg/ml vs. 10.3 +/- 0.5 microg/ml, p = 8.43 x 10
      (12), mean +/- SE). Simultaneous determination of hemodynamic and hemostatic
      parameters revealed that the only two parameters that were significantly
      correlated with the patients' plasma vWF concentrations were their pulmonary
      capillary wedge pressure (PCWP) and heart rate, suggesting a relationship between
      hemodynamic changes induced by the onset of myocardial infarction and the vWF
      plasma concentrations. Serial determinations revealed that the vWF concentrations
      had not changed 1 h after reperfusion therapy, but that they significantly
      increased by 24 to 72 h. The distribution of the larger multimers of vWF also
      increased in the acute and subacute phase. The vWF concentration and multimer
      distribution normalized 14 days after the onset of the myocardial infarction. Our
      findings suggest that the vWF concentration increased in acute myocardial
      infarction patients, possibly in association with the hemodynamic deterioration
      that occurs in acute myocardial infarction.

PMID- 10959691
TI  - Acute exacerbations of chronic obstructive pulmonary disease are accompanied by
      elevations of plasma fibrinogen and serum IL-6 levels.
AB  - BACKGROUND: Respiratory tract infections may acutely increase risk from coronary
      heart disease (CHD), though the mechanisms have not been defined. Patients with
      chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations
      that are often associated with respiratory infections. These patients also have
      increased cardiovascular morbidity and mortality. We hypothesized that transient
      acute increases in plasma fibrinogen, an independent risk factor for CHD, could
      occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a
      mechanism linking respiratory infection to risk of coronary heart disease.
      METHODS: 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed
      regularly over one year, with daily diary card monitoring of respiratory symptoms
      and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC
      2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was
      measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6)
      levels. RESULT: At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9
      (0.67) g/l in the 67 patients with exacerbations during the study and the median
      (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74)
      g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95)
      pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at
      exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed
      significantly greater rises in fibrinogen when exacerbations were associated with
      purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p =
      0.019) and symptomatic colds (b = 0.228; p = 0.024). CONCLUSIONS: Plasma
      fibrinogen levels were elevated in stable patients with COPD and may contribute
      to the increased cardiovascular morbidity and mortality in these patients. COPD
      exacerbations increased serum IL-6 levels, leading to a rise in plasma
      fibrinogen. Thus acute rather than chronic infection may have a role in
      predisposing to coronary heart disease or stroke.

PMID- 10959692
TI  - The Factor VIII acute phase response requires the participation of NFkappaB and
      C/EBP.
AB  - Coagulation Factor VIII is an acute phase protein in humans that has recently
      been shown to be transcriptionally responsive to interleukin-6. In this study, we
      have demonstrated that the human Factor VIII promoter is activated in cultured
      hepatocytes exposed to bacterial lipopolysaccharide (LPS). Deletion analysis has
      narrowed the LPS-responsive element of the Factor VIII promoter to a small region
      which contains two C/EBP binding sites and an adjacent NFkappaB binding site.
      Mutation of the downstream C/EBP site reduces LPS-responsiveness by approximately
      50%, while mutation of the NFkappaB binding site completely eliminates LPS
      responsiveness. While binding of C/EBPbeta and NFkappaB is still observed in gel
      retardation studies using acute phase nuclear extracts and a probe containing
      mutations to the downstream C/EBP site, neither NFkappaB nor C/EBP appear to bind
      to a probe in which the NFkappaB site has been mutated. Conservation of this
      region of the Factor VIII promoter in species which exhibit an increase in Factor
      VIII levels in response to inflammatory stimuli suggests that these transcription
      factor binding sites are important for normal regulation of the Factor VIII gene
      under conditions of stress.

PMID- 10959693
TI  - Normalisation of tissue factor pathway inhibitor activity after glycaemic control
      optimisation in type 1 diabetic patients.
AB  - Increased plasma concentrations of various markers of endothelial damage have
      been observed in type I diabetic patients, particularly in those with
      microangiopathy. OBJECTIVE: To evaluate the effect of near-normalisation of
      glycaemic control on different markers of endothelial injury involved in
      haemostasis in poorly-controlled type 1 diabetic patients. MATERIAL AND METHODS:
      TFPI, thrombomodulin (TM), plasminogen activator inhibitor, tissue-type
      plasminogen activator and von Willebrand factor were measured in 14 poorly
      controlled type 1 diabetic patients free of diabetes-related complications (8
      men, 6 women; mean age 29.8 +/- 9.9 years) before (baseline) and after 3 months
      of intensive therapy and in 14 sex-, age- and BMI-matched control subjects.
      RESULTS: After a mean follow-up of 107 +/- 49 days (56-210), HbA1c decreased from
      11.2 +/- 2.3 to 6.7 +/- 0.7% (p <0.0001). TFPI activity at baseline was higher
      than in the control group (126.9 +/- 34 vs 92.0 +/- 13%, p <0.005) and decreased
      after good glycaemic control was achieved (p <0.005), becoming similar to that in
      the control group (91.0 +/- 16.5%). The TFPI descent correlated with the
      variations observed in HbA1c (p <0.05; r = 0.54). TM levels at baseline were
      significantly higher than in the control group (42.3 +/- 9.1 vs 29.00 +/- 10.9; p
      <0.005) and did not change. The remaining parameters studied were similar between
      patients and controls and did not change after glycaemic optimisation.
      CONCLUSIONS: Optimisation of glycaemic control normalises the increased activity
      of TFPI but not the higher TM levels observed in poorly-controlled type I
      diabetic patients without chronic complications.

PMID- 10959694
TI  - Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune
      women with unexplained recurrent primary early foetal loss. The Nimes
      Obstetricians and Haematologists Study--NOHA.
AB  - Various antiphospholipid and/or antiprotein antibodies have been suspected to be
      associated with recurrent early foetal loss in absence of any habitual aetiology.
      We conducted a hospital-based case control study on women with no antecedent of
      thromboembolic or autoimmune disease. We studied 3 groups of 518 women: patients
      with unexplained primary recurrent early foetal loss, patients with explained
      episodes and mothers with no previous obstetrical accident. Matching the 3 groups
      was carried out on the basis of age, number or pregnancies and time elapsed since
      the end of the last pregnancy. Significant biological markers were then
      prospectively tested. The various antibodies were shown to be dependent on parity
      and on the presence of previous foetal loss: cut-off values were thus calculated
      using data obtained from the group of explained accidents, and adjusted for
      parity. Only anti-phosphatidylethanolamine IgM [odds ratio: 6.0, 95% confidence
      interval (2.3-15.7), p = 0.0003], anti-beta2-glycoprotein I IgG [4.4, (1.6-11.7),
      p = 0.0035] anti-annexin V IgG antibodies [3.2 (1.2-8.1), p = 0.015] and lupus
      anticoagulant [3.0, (1.3-6.8), p = 0.009], were found to be independent
      retrospective risk factors for unexplained early foetal loss. These four markers
      were subsequently found to be, during the following pregnancy, associated with a
      significant risk of foetal loss despite a low-dose aspirin treatment. In non
      thrombotic, non-auto-immune women with unexplained primary recurrent early foetal
      loss, subgroups of patients with positive anti-phosphatidylethanolamine IgM
      antibodies, or positive anti-beta2-glycoprotein-I IgG antibodies, or positive
      anti-annexin V IgG antibodies or lupus anticoagulant must be particularised. This
      should allow therapeutic trials to be carried in well-defined patients.

PMID- 10959695
TI  - Heparin-protamine complexes and C-reactive protein induce activation of the
      classical complement pathway: studies in patients undergoing cardiac surgery and
      in vitro.
AB  - The administration of protamine to patients undergoing cardiopulmonary bypass
      (CPB) to neutralize heparin and to reduce the risk of bleeding, induces
      activation of the classical complement pathway mainly by heparin-protamine
      complexes. We investigated whether C-reactive protein (CRP) contributes to
      protamine-induced complement activation. In 24 patients during myocardial
      revascularization, we measured complement, CRP, and complement-CRP complexes,
      reflecting CRP-mediated complement activation in vivo. We also incubated plasma
      from healthy volunteers and patients with heparin and protamine in vitro to study
      CRP-mediated complement activation. During CPB, CRP levels remained unchanged
      while C3 activation products increased. C4 activation occurred after protamine
      administration. CRP-complement complexes increased at the end of CPB and upon
      protamine administration. Incubation of plasma with heparin and protamine in
      vitro generated complement-CRP complexes, which was blocked by phosphorylcholine
      and stimulated by exogenous CRP. C4d-CRP complex formation after protamine
      administration correlated clinically with the incidence of postoperative
      arrhythmia. Protamine administration during cardiac surgery induces complement
      activation which in part is CRP-dependent, and correlates with postoperative
      arrhythmia.

PMID- 10959696
TI  - A new T-287C polymorphism in the 5' regulatory region of the tissue factor
      pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms
      with coronary artery disease and plasma TFPI levels.
AB  - Tissue factor pathway inhibitor (TFPI) is an important regulator of the extrinsic
      blood coagulation pathway. We screened the untranslated 5' region of the TFPI
      gene for polymorphisms and investigated their possible involvement in arterial
      thrombosis. The allele frequencies of a new polymorphism, located 287 base pairs
      upstream of the transcription start site (T-287C), and that of the previously
      described C-399T polymorphism, were similar in cases and controls. In controls,
      the -287C allele was associated with significantly higher levels of total TFPI
      antigen, arguing for an effect of this polymorphism on TFPI gene expression. In
      controls, the C-399T polymorphism did not alter TFPI levels. In the cases,
      however, decreased total and post-heparin free TFPI levels and increased F1+2
      levels were significantly associated with the -399T allele. These findings
      suggest that the T-287C and C-399T polymorphisms are not associated with an
      increased risk of coronary heart disease, a result which should be confirmed by a
      larger study. However, their influence on outcome, or a link with subtypes of
      acute coronary syndromes, cannot be excluded.

PMID- 10959697
TI  - Molecular characterisation and three-dimensional structural analysis of mutations
      in 21 unrelated families with inherited factor VII deficiency.
AB  - Factor VII (FVII) is a four-domain glycoprotein that plays a critical role in the
      initiation of blood coagulation. Hereditary deficiencies of this plasma protein
      results in a bleeding diathesis that varies in severity amongst affected
      patients. We have analysed the FVII gene in 27 patients with FVII deficiency from
      21 unrelated families predominantly of Middle-Eastern extraction. A total of 19
      different mutations were identified, of which 12 were novel and 7 had been
      previously reported. Nine of the 12 novel mutations were missense mutations
      located in the Gla domain (Ser23Pro), the second epidermal growth factor domain
      (Cys135Arg) and the catalytic serine protease domain (Arg247Cys, Arg277Cys,
      Ser282Arg, Pro303Thr, Ser363Ile, Trp364Cys, Trp364Phe), of which five are
      homozygous. Three novel splice mutations were identified in intron 1a (IVS1a+5),
      intron 2 (IVS2+1) and intron 6 (IVS6+1). Of the seven previously reported
      mutations, five were missense mutations of which three are homozygous (Gln100Arg,
      Arg152Gln, Arg304Gln, Cys310Phe and Thr359Met), one was a 17 bp deletion
      (10585del117bp) and one was a splice site mutation within intron 7 (IVS7+7). This
      study has significantly extended the current database of FVII mutations,
      including the number of known homozygous mutations. Conformational analyses of
      crystal structures for FVIIa and the FVIIa-tissue factor complex provided likely
      explanations for the effect of the missense mutations on FVIIa secretion or
      function. In particular, since 23 missense mutations were located to the serine
      protease domain, mostly to the region between the catalytic triad and the contact
      surface with tissue factor, this showed that the orientation of the serine
      protease domain relative to bound tissue factor in the complex is crucial for
      functional activity.

PMID- 10959698
TI  - A collaborative study to establish the 2nd International Standard for Fibrinogen,
      Plasma.
AB  - An International Collaborative Study involving 12 laboratories in 7 different
      countries was undertaken in order to replace the 1st International Standard (IS)
      for Fibrinogen, Plasma (89/644). The candidate replacement standard was the
      ampouled and freeze-dried residue of solvent/detergent treated plasma and was
      calibrated as coded duplicates (A and B) versus the 1st IS Fibrinogen, Plasma by
      automated Clauss assay and by a recommended clot collection (gravimetric) assay.
      This latter method had been used to calibrate the 1st IS Fibrinogen, Plasma.
      Comparing the ratios of the potency estimates of sample A to sample B (the coded
      duplicates), all of the laboratories obtained a ratio within 5% of the expected
      value of 1.0 by automated Clauss assay, which suggests that the laboratories were
      able to perform this assay well. Scrutiny of the data obtained from the
      gravimetric assays revealed that in almost all cases the results were invalid.
      The results of these assays are included in this report but clearly should be
      treated with caution and indeed produced significantly lower mean estimates of
      potency than the other assay methods. The overall geometric mean of all estimates
      of potency of the proposed 2nd IS Fibrinogen, Plasma (98/612) is 2.19 mg/ampoule
      by the automated Clauss assay. These data have been presented to the Fibrinogen
      Sub-Committee of the Standardisation and Scientific Committee (SSC) of the
      International Society on Thrombosis and Haemostasis (ISTH) (Washington, DC,
      August 1999), which recommended the establishment of 98/612 as the 2nd IS
      Fibrinogen, Plasma. This report has been presented to the Expert Committee on
      Biological Standardisation of the World Health Organisation (ECBS-WHO) at their
      1999 session and 98/612 was established as the 2nd IS Fibrinogen, Plasma with a
      potency of 2.2 mg/ampoule.

PMID- 10959699
TI  - Fibrinogen Caracas V, an abnormal fibrinogen with an Aalpha 532 Ser-->Cys
      substitution associated with thrombosis.
AB  - A new dysfibrinogenemia associated with thrombophilia has been identified in a
      Venezuelan kindred. Thrombin and Reptilase times were prolonged and the
      accelerating capacity of the patient's fibrin on the t-PA-induced plasminogen
      activation was decreased. In addition the affinity of fibrinogen for plasminogen
      was diminished. Permeability and electron microscopy studies revealed that the
      abnormal clot was made up of thin and densely packed fibres giving rise to a
      reduced fibrin gel porosity. This was confirmed by turbidity studies showing a
      decreased fibre mass/length ratio. Affected members were heterozygous for an
      Aalpha 532 Ser-->Cys mutation as demonstrated by genetic analyses. This abnormal
      fibrinogen has been designated as Fibrinogen Caracas V. The family study showed a
      convincing association between the mutation and thrombotic manifestations. The
      thrombotic tendency may be ascribed to lack of accelerating capacity of fibrin to
      induce fibrinolysis caused by an abnormal clot structure with thin fibres and
      reduced porosity.

PMID- 10959700
TI  - The second laminin G-type domain of protein S is indispensable for expression of
      full cofactor activity in activated protein C-catalysed inactivation of factor Va
      and factor VIIIa.
AB  - Vitamin K-dependent protein S is a cofactor to the anticoagulant serine protease
      activated protein C (APC) in the proteolytic inactivation of the procoagulant,
      activated factor V (FVa) and factor VIII (FVIIIa). In the FVa degradation,
      protein S selectively accelerates the cleavage at Arg306, having no effect on the
      Arg506 cleavage. In the FVIIIa inactivation, the APC-cofactor activity of protein
      S is synergistically potentiated by FV, which thus has the capacity to function
      both as a pro- and an anticoagulant protein. The SHBG-like region of protein S,
      containing two laminin G-type domains, is required for the combined action of
      protein S and FV. To elucidate whether both G domains in protein S are needed for
      expression of APC-cofactor activities, chimeras of human protein S were created
      in which the individual G domains were replaced by the corresponding domain of
      the homologous Gas6, which in itself has no anticoagulant activity. In a plasma
      based assay, chimera I (G1 from Gas6) was as efficient as wild-type recombinant
      protein S, whereas chimera II (G2 from Gas6) was less effective. The synergistic
      cofactor activity with FV in the inactivation of FVIIIa was lost by the
      replacement of the G2 domain in protein S (chimera II). However, chimera I did
      not exert full APC-cofactor activity in the FVIIa degradation, indicating
      involvement of both G domains or the entire SHBG-like region in this reaction.
      Chimera I was fully active in the degradation of FVa in contrast to chimera II,
      which exhibited reduced cofactor activity compared to protein S. In conclusion,
      by using protein S-Gas6 chimeric proteins, we have identified the G2 domain of
      protein S to be indispensable for an efficient inactivation of both FVIIa and
      FVa, whereas the G1 domain was found not to be of direct importance in the FVa
      inactivation experiments.

PMID- 10959701
TI  - Anticoagulant activity and pharmacokinetic properties of a sub-cutaneously
      administered mixed micellar formulation of argatroban in experimental animals.
AB  - We have studied the anticoagulant properties of a novel mixed micellar
      formulation containing 14 mg/ml argatroban administered by the sub-cutaneous
      (s.c.) route to rats, rabbits, dogs and primates. Blood samples were taken at
      various times post-treatment for the determination of the thrombin time (TT),
      Ecarin clotting time (ECT) and the activated partial thromboplastin time (aPTT).
      Plasma levels of argatroban were determined in the dog and primate. Mixed
      micelles alone (0.15 M sodium glycocholate and 0.15 M egg lecithin) were without
      effect on the clotting parameters. The mixed micellar formulation of argatroban
      dose-dependently increased all three clotting parameters in the rat (1-4 mg/kg),
      the rabbit (1 and 2 mg/kg), the dog (1 and 2 mg/kg) and the primate (0.25 and 0.5
      mg/kg). In each case the TT was the most sensitive parameter, followed by the ECT
      and the aPTT. The duration of action of argatroban in each species was dose
      dependent and varied from 3 h in the rat to 6 h in the dog. In the latter, the
      mixed micelle formulation had a significantly increased plasma half-life and mean
      residence time without affecting the overall area under the curve. The increases
      in the clotting time were strongly correlated with the plasma levels of
      argatroban and were linear across the range of concentrations obtained in the dog
      and the primate, although the aPTT plasma concentration response curve was very
      flat. Species differences were noted between the increase in clotting time for a
      given plasma concentration, with the primate being more sensitive than the dog
      (e.g. 4.7 times more so in terms of the ECT). Thus, a mixed micellar formulation
      of argatroban, which markedly enhances its solubility, could be useful as a
      potential anticoagulant for sub-cutaneous administration.

PMID- 10959702
TI  - Activity of a sub-cutaneously administered novel mixed micellar formulation of
      argatroban in rat and rabbit models of venous thrombosis.
AB  - We studied the antithrombotic activity of a mixed micellar formulation containing
      14 mg/ml argatroban administered by the subcutaneous (s.c.) route in rat and
      rabbit models of venous thrombosis. The effects on bleeding time in the rat tail
      transection bleeding time test were also studied. In a tissue factor-dependent
      arterio-venous shunt model, argatroban treatment led to dose-dependent reduction
      in thrombus weight with an estimated ID50 of 1.8 mg/kg s.c. In the same model,
      heparin had an estimated ID50 of 179 IU/kg. The antithrombotic activity of
      argatroban was accompanied by increases in the thrombin and ecarin clotting times
      but not the aPTT, whereas heparin increased the thrombin time and aPTT but not
      the ecarin clotting times. Argatroban also inhibited thrombus formation in a
      rabbit model of thromboplastin + stasis induced thrombosis in the rabbit jugular
      vein with an estimated ID50 of 1 mg/kg s.c. When tested in the rat tail
      transection bleeding time test, the mixed micellar formulation of argatroban
      caused significant increases in the bleeding time as from 8 mg/kg s.c., while
      heparin significantly increased the bleeding time at 800 U/kg. Mixed micellar
      argatroban appears to have a superior safety margin to heparin in terms of
      antithrombotic efficacy and bleeding risk. Thus, a mixed micellar formulation of
      argatroban, which markedly enhances its solubility, could be useful as a
      potential antithrombotic agent for subcutaneous administration.

PMID- 10959703
TI  - Fluid shear stress increases the intra-cellular storage pool of tissue-type
      plasminogen activator in intact human conduit vessels.
AB  - We investigated the effect of shear stress on the expression of tissue-type
      plasminogen activator (t-PA) in intact human conduit vessels. Human umbilical
      veins were exposed to high or low shear stress (25 vs < 4 dyn/cm2) at identical
      intraluminal pressure (20 mmHg) for 1.5, 3, and 6 h in a new computerized
      biomechanical perfusion system. High shear perfusion induced a marked, time
      dependent increase in t-PA immunostaining in both the endothelium and the media.
      t-PA relative to GAPDH gene expression increased by 54 +/- 14% in high- compared
      to low-sheared vessels (p = 0.002). By contrast, t-PA release into the perfusion
      medium was similar in vessels perfused under high or low shear stress conditions.
      The results show that shear stress independently of pressure is a potent fluid
      mechanical stimulus for up-regulation of the intracellular storage pool of t-PA
      in the vascular wall of fresh human conduit vessels. The shear effect is
      associated with an increased t-PA gene expression.

PMID- 10959704
TI  - Assay of functional plasminogen in rat plasma applicable to experimental studies
      of thrombolysis.
AB  - An improved sensitive, specific, precise and accurate assay of plasminogen in rat
      plasma was developed. It is performed in 96-well microtiter plates and can be
      completed within one hour. The assay is based on activation of plasminogen by
      human urokinase-type plasminogen activator (uPA) and simultaneous measurement of
      generated plasmin with the specific plasmin substrate H-D-Val-Phe-Lys-4
      nitroanilide (S-2390), using purified native rat plasminogen for calibration. The
      concentration of S-2390 in the final reaction mixture during the whole reaction
      period is much greater than the Km value (approximately 20 microM) for rat
      plasmin-cleavage of S-2390 ensuring that hydrolysis of substrate follows zero
      order kinetics and that the substrate produces a 20-35 fold decrease in rate of
      inhibition of plasmin by its target inhibitors in plasma. Analogous to the human
      system the target plasma inhibitors of rat plasmin are shown to be plasmin
      inhibitor and alpha-macroglobulins. Tranexamic acid (0.8 mM) is incorporated in
      the reaction mixture resulting in a 19-fold increase in the rate of plasminogen
      activation and presumably an about 50-fold decrease in the rate of inhibition of
      generated plasmin by plasmin inhibitor. The assay is suitable for accurate
      measurement of plasminogen in samples obtained from animals containing
      pharmacological concentrations of uPA or tissue-type plasminogen activator (tPA)
      in their plasma when in vitro plasminogen activation is blocked at pH 5 by
      collecting blood in acidic anticoagulant. Judged from in vitro experiments
      formation of catalytic active plasmin-alpha-macroglobulin complexes during
      massive activation of plasminogen in vivo does not interfere with the assay.

PMID- 10959705
TI  - A novel point mutation of the splicing donor site in the intron 2 of the plasmin
      inhibitor gene.
AB  - Plasmin inhibitor (PI) is a major physiological inhibitor of plasmin-mediated
      fibrinolysis; hence, its deficiency results in a severe haemorrhagic diathesis.
      We analyzed the PI gene of a French boy apparently homozygous for PI deficiency
      and his heterozygous parents. Both alleles of the homozygous patient had a novel
      G to A transition at the consensus splicing donor site in the intron 2 of the PI
      gene. In an expression assay using the heterologous cells transfected with the
      mutant PI expression vector, 3 types of aberrant transcripts using a cryptic
      splicing donor site within the intron 2 were detected. All of these mRNAs had a
      stop codon upstream of the cryptic splicing site and encode only 25 amino acids,
      comprising the first 21 amino acids of the signal peptide (27 amino acids) plus 4
      new amino acids. This mutant was designated as PI-Paris-Trousseau.

PMID- 10959706
TI  - Ultrastructural analysis of megakaryocytes in GPV knockout mice.
AB  - Lesions in the genes for GPIb alpha, GPIb beta or GPIX result in a bleeding
      diathesis, the Bernard-Soulier syndrome (BSS), which associates a platelet
      adhesion defect with thrombocytopenia, giant platelets and abnormal
      megakaryocytes (MK). The role of GPV, also absent in BSS, was recently addressed
      by gene targeting in mice. While a negative modulator function for GPV on
      thrombin-induced platelet responses was found in one model, the absence of GP V
      had no effect on GPIb-IX expression or platelet adhesion. Our study extends
      previous results and reports that electron microscopy of bone marrow from the GPV
      knockout mice revealed a normal MK ultrastructure and development of the
      demarcation membrane system (DMS). There was a usual presence of MK fragments in
      the bone marrow vascular sinus. Immunogold labelling of MK from the knockout mice
      showed a normal distribution of GPIb-IX in the DMS and on the cell surface. The
      distribution of fibrinogen, vWF and P-selectin was unchanged with, interestingly,
      P-selectin also localised within the DMS in both situations. Thus GPV is not
      crucial to MK development and platelet production, consistent with the fact that
      no mutation in the GPV gene has as yet been described in BSS.

PMID- 10959707
TI  - Procoagulant activity of endothelial cells after infection with respiratory
      viruses.
AB  - Influenza virus epidemics are associated with excess mortality due to
      cardiovascular diseases. There are several case reports of excessive coagulation
      during generalised influenza virus infection. In this study, we demonstrate the
      ability of respiratory viruses (influenza A, influenza B, parainfluenza-1,
      respiratory syncytial virus, adenovirus, cytomegalovirus) to infect lung
      fibroblasts and human umbilical vein endothelial cells in culture. All viral
      pathogens induced procoagulant activity in infected endothelial cells, as
      determined in a one-stage clotting assay, by causing an average 55% reduction in
      the clotting time. When factor VII deficient plasma was used clotting time was
      not reduced. The induction of procoagulant activity was associated with a 4- to 5
      fold increase in the expression of tissue factor, as measured by the generation
      of factor Xa. Both experiments indicate that the procoagulant activity of
      endothelial cells in response to infection with respiratory viruses is caused by
      upregulation of the extrinsic pathway. Although both enveloped viruses and a non
      enveloped virus (adenovirus) induced procoagulant activity in endothelial cells
      by stimulating tissue factor expression, the role of the viral envelope in the
      assembly of the prothrombinase complex remains uncertain. We conclude that both
      enveloped and non-enveloped respiratory viruses are capable of infecting cultured
      human endothelial cells and causing a shift from anticoagulant to procoagulant
      activity associated with the induction of tissue factor expression.

PMID- 10959708
TI  - Endothelial cell seeding on crosslinked collagen: effects of crosslinking on
      endothelial cell proliferation and functional parameters.
AB  - Endothelial cell seeding, a promising method to improve the performance of small
      diameter vascular grafts, requires a suitable substrate, such as crosslinked
      collagen. Commonly used crosslinking agents such as glutaraldehyde and
      formaldehyde cause, however, cytotoxic reactions and thereby hamper
      endothelialization of currently available collagen-coated vascular graft
      materials. The aim of this study was to investigate the effects of an alternative
      method for crosslinking of collagen, using N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS), on
      various cellular functions of human umbilical vein endothelial cells (HUVECs) in
      vitro. Compared to non-crosslinked type I collagen, proliferation of seeded
      endothelial cells was significantly increased on EDC/NHS-crosslinked collagen.
      Furthermore, higher cell numbers were found with increasing crosslink densities.
      Neither the morphology of the cells nor the secretion of prostacyclin (PGI2), von
      Willebrand factor (vWF), tissue plasminogen activator (t-PA) and plasminogen
      activator inhibitor (PAI-1) was affected by the crosslink density of the collagen
      substrate. Therefore, EDC/NHS-crosslinked collagen is candidate substrate for in
      vivo application such as endothelial cell seeding of collagen-coated vascular
      grafts.

PMID- 10959709
TI  - Modulation of vascular human endothelial and rat smooth muscle cell growth by a
      fucosylated chondroitin sulfate from echinoderm.
AB  - Fucosylated chondroitin sulfate is a glycosaminoglycan extracted from the sea
      cucumber Ludwigothurea grisea. This polysaccharide has the same structure as a
      mammalian chondroitin sulfate but some of the glucuronic acid residues display
      sulfated fucose branches. Anticoagulant and antithrombotic properties of
      fucosylated chondroitin sulfate have already been described. In order to further
      investigate its potential therapeutic use as an antithrombotic agent, we studied
      its effect on vascular smooth muscle cell (SMC) proliferation and endothelial
      cell proliferation, migration and Tissue Factor Pathway Inhibitor (TFPI) release.
      The experiments were performed on SMC from rat thoracic aorta and on human
      umbilical vein endothelial cell (HUVEC) in culture with or without added
      fibroblast growth factors (FGF-1 and FGF-2). Our results showed that: (i)
      fucosylated chondroitin sulfate had a strong inhibitory effect on SMC
      proliferation (IC50 =10 +/- 5 microg/ml) and (ii) no effect on HUVEC
      proliferation and migration assays, in the absence of exogenous FGF, while
      heparin had inhibitory effects; (iii) fucosylated chondroitin sulfate (10
      microg/ml) enhanced FGF-1 and FGF-2 induced HUVEC proliferation by 45% (145.4 +/-
      7.2%) and 27% (126.9 +/- 4.2%), respectively; (iv) on FGF-induced HUVEC
      migration, fucosylated chondroitin sulfate (10 microg/ml) had a strong enhancing
      effect with FGF-1, +122% (222.2 +/- 15.8%), three times higher than that of
      heparin, and a lower enhancing effect with FGF-2, +43% (142.7 +/- 4.6%), whereas
      heparin had no effect; (v) fucosylated chondroitin sulfate stimulated TFPI
      release, mainly on the free form. +98% (198.2 +/- 25%). In addition, the
      structural features of the polysaccharide associated with its biological activity
      were resolved using chemically modified fucosylated chondroitin sulfates.
      Sulfated fucose branches groups are essential to the potentiating effect of the
      polysaccharide on HUVEC proliferation and migration. Surprisingly, removal of
      fucose branches from the fucosylated chondroitin sulfate did not abolish TFPI
      release. Finally, partial reduction of the glucuronic acid carboxyl groups
      limited the potentiating effect on HUVEC proliferation and migration but did not
      affect TFPI release. In conclusion, this fucosylated chondroitin sulfate from
      invertebrate origin reveals useful properties for an antithrombotic agent:
      inhibition of SMC proliferation, enhancement of endothelium wound repair and TFPI
      release. These properties on vascular cells, associated with a low bleeding
      tendency and an antithrombotic activity, strongly suggest its potential use as a
      new therapeutic agent in arterial thrombosis and restenosis, with a more
      favorable effect than heparin.

PMID- 10959710
TI  - Human carotid artery smooth muscle cells rarely express alpha(v)beta3 integrin at
      sites of recent plaque rupture.
AB  - Fibrin(ogen) is the major matrix ligand for beta3 integrins. If alpha(v)beta3 is
      the major receptor for fibrin(ogen) on intimal smooth muscle cells, we might
      expect to see this integrin associated with fibrin(ogen). Eighty-four specimens
      obtained from endarterectomies of 14 patients were studied. Fibrin was frequently
      observed in carotid intima even at the non-atherosclerotic areas. As for beta1
      and beta3 integrins, beta1 was predominant in intima. The alpha(v)beta3 integrin
      expression was less frequent than alpha5beta1, another receptor for fibrin(ogen),
      in diffuse intimal thickening, fibrous cap and advanced plaques. Furthermore,
      alpha(v)beta3 was generally negative on smooth muscle cells in recent plaque
      ruptures. In conclusion, we suggest more attention should be paid on abundant
      fibrin matrix in intima. Histologically, the alpha5beta1 integrin rather than the
      alpha(v)beta3 is the major receptor for fibrin in intimal smooth muscle cells.

PMID- 10959711
TI  - Acquired von Willebrand syndrome: data from an international registry.
AB  - The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with
      laboratory findings similar to those of congenital von Willebrand disease (vWD).
      Despite the numerous cases reported in the literature until 1999 (n = 266), large
      studies on AvWS are not available. Moreover, diagnosis of AvWS has been difficult
      and treatment empirical. These considerations prompted us to organize an
      international registry. A questionnaire, devised to collect specific information
      on AvWS, was sent to all the members of the International Society on Thrombosis
      and Haemostasis (ISTH), who were invited to respond if they had diagnosed cases
      with the AvWS cases. 156 members answered the questionnaire and 54 of them sent
      information on 211 AvWS cases from 50 centers. Data were compared with those
      already published in the literature and 25 cases already described or not
      correctly diagnosed were excluded. The 186 AvWS cases that qualified for the
      registry were associated with lymphoproliferative (48%) and myeloproliferative
      disorders (15%), neoplasia (5%), immunological (2%), cardiovascular (21%) and
      miscellaneous disorders (9%). Ristocetin cofactor activity (vWF:RCo) or collagen
      binding activity (vWF:CBA) were usually low in AvWS (median values 20 U/dL, range
      3-150), while factor VIII coagulant activity was sometimes normal (median 25
      U/dL, range 3-191). FVIII/vWF inhibiting activities were present in only a
      minority of cases (16%). Bleeding episodes in AvWS were mostly of mucocutaneous
      type (68%) and were managed by DDAVP (32%), FVIII/vWF concentrates (37%),
      intravenous immunoglobulins (33%), plasmapheresis (19%), corticosteroids (19%)
      and immunosuppressive or chemotherapic agents (35%). Based upon the data of this
      international registry, it appears that AvWS is especially frequent in lympho- or
      myeloproliferative and cardiovascular diseases. Therefore, AvWS should be
      suspected and searched with the appropriate laboratory tests especially when
      excessive bleeding occurs in patients with these disorders. On the basis of the
      information provided by this registry guidelines for diagnosis and management of
      the AvWS are given.

PMID- 10959712
TI  - An additional unique candidate mutation (G2470A; M740I) in the original families
      with von Willebrand disease type 2 M Vicenza and the G3864A (R1205H) mutation.

PMID- 10959713
TI  - Pregnancy in women with type 1 von Willebrand disease caused by heterozygosity
      for von Willebrand factor mutation C1130F.

PMID- 10959714
TI  - Absence of circulating factor IX antigen in hemophilia B dogs of the UNC-Chapel
      Hill colony.

PMID- 10959715
TI  - What clinical significance has the presence of the homozygous G20210A prothrombin
      gene mutation in a healthy woman?

PMID- 10959716
TI  - The factor V Leiden and prothrombin G20210A mutations in Kirghiz population.

PMID- 10959717
TI  - Heterogeneity of activated protein C resistance phenotype in subjects with
      compound heterozygosity for HR2 haplotype and FV Leiden mutation (R506Q) in
      factor V gene.

PMID- 10959718
TI  - Mesenteric-portal vein thrombosis in a patient with hyperhomocysteinemia and
      heterozygous for 20210A prothrombin allele.

PMID- 10959719
TI  - Oral ethinyl estradiol, but not transdermal 17beta-estradiol, increases plasma C
      reactive protein levels in men.

PMID- 10959720
TI  - The human platelet alloantigen 5 polymorphism as a risk for the development of
      acute idiopathic thrombocytopenia purpura.

PMID- 10959721
TI  - Zentralblatt fur Bakteriologie--100 years ago: evidence for a haemolysin produced
      by Pseudomonas aeruginosa.

PMID- 10959722
TI  - Host factors that influence the behaviour of bacterial pathogens in vivo.
AB  - Interest is increasing in how bacteria behave and produce virulence determinants
      within the infected host. There are three aspects of this process; observations
      on the bacteria themselves, recognition of host factors that affect them and
      investigation of metabolic interactions between the two. The first aspect is
      relatively easy to investigate and attracts much interest. The second and third
      are difficult to work on and hence understudied. The review aims to stimulate
      interest in them by indicating methods of investigation and describing some
      successful studies. After discussing host factors that determine growth in vivo
      consideration is given to factors that influence the production of the
      determinants of mucosal colonization, penetration, interference with host defence
      and damage to the host. The final section deals with the influence of host
      derived cytidine 5'-monophospho-N-acetyl neuraminic acid and lactate on the
      pathogenicity of gonococci, meningococci and Haemophilus influenzae.

PMID- 10959723
TI  - Fimbriae-assisted bacterial surface display of heterologous peptides.
AB  - The display of peptide segments on the surface of bacteria offers many new and
      exciting applications in biotechnology and medical research. Fimbria-assisted
      display of heterologous sequences is a paradigm for chimeric organelle display on
      bacteria. Fimbriae are particularly attractive candidates for epitope display for
      several reasons: (1) they are present in extremely high numbers at the cell
      surface, (2) they are strong immunogens, (3) they possess inherent adhesive
      properties, and (4) they can be easily purified. The majority of work dealing
      with fimbria-assisted peptide display has been focused on the development of
      recombinant vaccines. A number of different fimbrial types have been used to
      display immune-relevant sectors of various foreign proteins. Chimeric fimbrial
      vaccines can be used in the context of purified proteins, however the potential
      also exists to exploit this technology for the development of live recombinant
      vaccines. Work has also been performed demonstrating the amenability of fimbriae
      towards the powerful technology of random peptide display. This review summarises
      the current state of research in this field.

PMID- 10959724
TI  - Peptide display on bacterial flagella: principles and applications.
AB  - Expression of foreign peptides as fusions to bacterial cell surface proteins has
      gained increasing attention in basic, as well as applied research during the last
      decade. A wide range of heterologous peptides have been expressed, and the
      spectrum of available carrier proteins is also wide. The choice of carrier
      protein is frequently ruled by the application of the fusion protein constructed.
      This review is focused on flagella display, which is based on genetic fusion of
      foreign peptides into a surface-exposed, dispensable region of flagellin, the
      flagellar major subunit present in thousands of copies per filament. Expression
      of these constructs in flagellin-deficient host strains results in hybrid
      flagella carrying the heterologous peptides in thousands of intimately-associated
      copies. The first and still most frequent application of flagella display is the
      construction of novel recombinant vaccines. Flagella display has also been used
      in peptide display as an alternative to the phage-display technique. One
      application involves fusion into a disulfide loop of Escherichia coli thioredoxin
      that has been inserted into flagellin, this system facilitates expression of
      random peptides in a conformationally constrained manner readily accessible on
      the flagellar surface. The random peptide library has been applied in antibody
      epitope mapping and is suitable for biopanning procedures in the study of ligand
      receptor interactions. Many bacterial adhesins are of complex nature and thereby
      difficult to analyse by conventional methods. Direct flagella display has proven
      to be applicable also in bacterial adhesion technology since large fragments, up
      to 302 amino acid residues in length, of bacterial adhesins can be functionally
      expressed as fusions to flagellin. Hybrid flagella are easily purified and can
      easily be analysed for binding to various targets, such as immobilized proteins,
      tissue sections, as well as cell cultures.

PMID- 10959725
TI  - Molecular responses to changes in the environmental pH are conserved between the
      fungal pathogens Candida dubliniensis and Candida albicans.
AB  - In this work we cloned CdPHR1 and CdPHR2 from the human fungal pathogen Candida
      dubliniensis. The two genes are homologues to the pH-regulated genes PHR1 and
      PHR2 from Candida albicans. The pH-dependent pattern of expression of CdPHR1 and
      CdPHR2 was conserved in C. dubliniensis. CdPHR1 could be shown to be functionally
      equivalent to PHR1. The pH-regulated mode of expression was maintained when
      CdPHR1 was integrated in C. albicans. This indicates a fundamentally similar mode
      of expressional regulation in the two species. CdPHR1 was furthermore capable of
      reversing the aberrant phenotype of a Saccharomyces cerevisiae GAS1 deletion
      mutant. In this species, however, expression of CdPHR1 was no longer under
      control of the external pH. Expression of CdPHR1 was not detected when it was
      introduced into Aspergillus nidulans. In conclusion, C. dubliniensis and C.
      albicans respond to changes in the environmental pH with a change in cell shape
      and differential gene expression.

PMID- 10959726
TI  - Characterization of the Legionella pneumophila gene ligA.
AB  - Legionella pneumophila is a bacterial pathogen that resides and multiplies in
      macrophages as well as in its natural aquatic hosts, the protozoa. Different
      bacterial factors contribute to pathogenicity and accompanying eukaryotic
      intracellular events. Sequencing of mip flanking regions revealed a gene of 2610
      bp, ligA, that has no significant similarity to any of the genes identified
      previously. Epidemiological studies indicate that this gene is present in
      Legionella pneumophila, the species most often associated with cases of the
      Legionnaires' disease, but not in Legionella species other than L. pneumophila.
      The isogenic ligA deletion mutant was resistant to NaCl, and showed decreased
      cytotoxicity to human monocytes and decreased hemolytic activity to red blood
      cells. However, the most prominent effect of the L. pneumophila ligA mutant
      strain LEPF1 was the nearly completely reduced replication within the natural
      host Acanthamoeba castellanii. Since this gene is L. pneumophila specific and
      regulates numerous bacterial properties we designated this gene ligA for
      Legionella pneumophila infectivity gene A.

PMID- 10959727
TI  - Molecular mechanics of the mycobacterial cell wall: from horizontal layers to
      vertical scaffolds.
AB  - Current models depicting the structural organization of the mycobacterial cell
      wall assume peptidoglycan and galactan strands to run in parallel to the
      cytoplasmic membrane forming several horizontal layers beneath perpendicularly
      oriented mycolic acids. Following a thorough re-evaluation of the currently
      available chemical, biochemical and electron microscopical data, we propose a
      fundamentally distinct principle of the physical organization and biosynthesis of
      the mycobacterial cell wall skeleton. According to this new concept, the solid
      and elastic matrix that makes the mycobacterial cell wall a formidably
      impermeable barrier is the direct consequence of cross-linked glycan strands
      which all run in a direction perpendicular to the cytoplasmic membrane.

PMID- 10959728
TI  - Interaction of alveolar macrophages with Staphylococcus aureus and induction of
      microbial L-forms during infection in rats.
AB  - In vivo cell interactions between Staphylococcus aureus and rat alveolar
      macrophages were investigated after intranasal inoculation during a 30-days
      period of examination. Some dynamic characteristics of microorganisms in the
      macrophages were examined by electron microscopy and acid phosphatase
      cytochemistry. It was found that at earlier infection intervals (days 3 and 7)
      the ingested cocci were sequestered in phagosomes and phagolysosomes and later
      many of the microbial cells were digested. An interesting finding was the
      intracellular appearance of cell wall-defective forms (L-forms) of S. aureus at
      later intervals (days 14 and 30 after challenge). Infection kinetics were
      evaluated by isolation and enumeration of colony-forming units of S. aureus from
      bronchoalveolar fluid and by assessment of blood and bronchoalveolar total and
      differential leukocyte counts. The results indicate that induction and survival
      of S. aureus L-forms may occur spontaneously in vivo. This phenomenon could
      explain some of the mechanisms, provoking the latent and relapsing lung
      infections.

PMID- 10959729
TI  - Clonal diversity of Shiga toxin-producing Escherichia coli O157:H7/H- in Germany-
      a ten-year study.
AB  - Two hundred and ten E. coli O157:H7/H- strains isolated from single cases and
      outbreaks of diarrhoea and haemolytic uraemic syndrome (HUS) in Germany between
      1988 and 1998 were characterised by a range of molecular subtyping methods and
      phage typing in order to analyse their clonal nature. A high clonal
      heterogeneity, together with a considerable clonal stability, has been identified
      among the bacterial isolates and no single clonal type appeared to be
      geographically dominant. It is recommended to apply pulsed-field gel
      electrophoresis (PFGE) together with P gene profile determination (number and
      genomic positions of lambdoid bacteriophages) as laboratory tools for an extended
      epidemiological surveillance of E. coli OOFF phage typing will remain helpful as
      a first line of analysis, particularly in outbreak situations.

PMID- 10959730
TI  - Early diagnosis of bubonic plague using F1 antigen capture ELISA assay and rapid
      immunogold dipstick.
AB  - Plague is still prevalent in more than 20 countries. Two F1 antigen diagnostic
      assays (an immunocapture ELISA and an immunogold chromatography dipstick) were
      evaluated using bubo aspirates, serum and urine specimens from patients suspected
      with plague. The specificity of the two F1 assays was found 100%. Using
      bacteriology as a gold reference diagnostic assay, 52 patients were Yersinia
      pestis culture positive and 141 negative. The sensitivity of the F1 ELISA test
      was 100% in bubo, 52% in serum and 58% in urine specimens. In culture negative
      patients, the F1 antigen could be found in 10% bubo aspirates, 5% serum and 7%
      urine specimens of culture negative patients for whom a seroconversion for anti
      F1 antibodies was also observed. The sensitivity of the dipstick assay was 98% on
      bubo aspirates specimens. Compared to the ELISA test, the agreement rate was
      97.5% and the correlation coefficient tau = 0.90 (p < 10(-3)). In conclusion, the
      diagnosis of bubonic plague has to be performed on bubo fluid rather than on
      serum or urine specimens. Both the F1 ELISA and the dipstick assays are valuable
      tools for an early diagnosis and for the surveillance of plague.

PMID- 10959731
TI  - Catalase-negative Actinomyces neuii subsp. neuii isolated from an infected
      mammary prosthesis.
AB  - In this case report a catalase-negative strain of Actinomyces neuii subsp. neuii
      is described as the possible causative agent of an infected mammary prosthesis.
      DNA hybridization studies and 16S rRNA analysis confirmed that the strain belongs
      to the species Actinomyces neuii subsp. neuii. Since this strain is the first A.
      neuii subsp. neuii strain reported to be catalase negative, the catalase reaction
      should no longer be considered a key reaction for the diagnosis of this species
      but must be interpreted in conjunction with other characteristics.

PMID- 10959732
TI  - Decontamination of a Mycoplasma-infected Chlamydia pneumoniae strain by pulmonary
      passage in SCID mice.
AB  - We describe a procedure to eliminate contaminating Mycoplasma from Chlamydia
      pneumoniae (C. pneumoniae) cultures by pulmonary passage in severe combined
      immunodeficiency mice (SCID). Four weeks after experimental infection only C.
      pneumoniae could be cultured from the lungs of the infected animals while
      Mycoplasma could not be detected any longer, as shown by PCR, culture and
      transmission electron microscopy (TEM).

PMID- 10959733
TI  - Procalcitonin as a marker of bacterial infection.

PMID- 10959734
TI  - Overdiagnosis and consequent mismanagement of head louse infestations in North
      America.
AB  - BACKGROUND: Lay personnel and many health care workers in the United States
      believe that head louse infestations caused by Pediculus capitis are exceedingly
      transmissible and that infested children readily infest others. Schoolchildren
      therefore frequently become ostracized and remain so until no signs of their
      presumed infestations are evident. Repeated applications of pediculicidal product
      and chronic school absenteeism frequently result. METHODS: To determine how
      frequently louse-related exclusions from schools and applications of
      pediculicidal therapeutic regimens might be inappropriate, we invited health care
      providers as well as nonspecialized personnel to submit specimens to us that were
      associated with a diagnosis of pediculiasis. Each submission was then
      characterized microscopically. RESULTS: Health care professionals as well as
      nonspecialists frequently overdiagnose pediculiasis capitis and generally fail to
      distinguish active from extinct infestations. Noninfested children thereby become
      quarantined at least as often as infested children. Traditional anti-louse
      formulations are overapplied as frequently as are "alternative" formulations.
      Pediculicidal treatments are more frequently applied to non-infested children
      than to children who bear active infestations. CONCLUSIONS: Pediculicidal
      treatments should be applied solely after living nymphal or adult lice or
      apparently viable eggs have been observed. Because health care providers as well
      as lay personnel generally misdiagnose pediculiasis, and because few symptoms and
      no direct infectious processes are known to result, we suggest that the practice
      of excluding presumably infested children from school may be more burdensome than
      the infestations themselves.

PMID- 10959735
TI  - Transmission of multidrug-resistant tuberculosis.
AB  - AIM: To compare the Mycobacterium tuberculosis isolates of adult index cases with
      multidrug-resistant (MDR) tuberculosis to the isolates obtained from their child
      contacts. PATIENTS AND METHODS: A 4-year prospective study in the Western Cape
      Province of South Africa. We evaluated 149 child contacts of 80 adult MDR
      pulmonary tuberculosis cases. This report includes those cases where a culture
      for M. tuberculosis was obtained from both the adult source case and the child
      contact. Isolates were compared by drug susceptibility pattern and restriction
      fragment length polymorphism analysis. RESULTS: Six adult-child pairs with
      cultures for M. tuberculosis were identified. Two children had contact with more
      than one adult tuberculosis case. One child received previous isoniazid
      prophylaxis. Drug susceptibility pattern and restriction fragment length
      polymorphism analysis were identical for five adult-child pairs. One child, with
      no other known source case, had a strain different from that of the identified
      source case, but the MDR M. tuberculosis strain with which he was infected was
      prevalent in the community in which he resided. All children responded well to
      treatment. CONCLUSION: This study confirms that most of the childhood contacts of
      adults with MDR tuberculosis are likely to be infected by these MDR source cases
      despite their exposure to other drug-susceptible adults with tuberculosis in some
      instances. Child contacts of adults with MDR tuberculosis should be treated
      according to the drug susceptibility patterns of the likely source cases' M.
      tuberculosis strains unless their own strain's susceptibility testing indicates
      otherwise. Contact tracing remains of fundamental importance in identifying
      children at risk.

PMID- 10959736
TI  - Tuberculosis in human immunodeficiency virus-infected and human immunodeficiency
      virus-exposed children in New York City. The New York City Pediatric Spectrum of
      HIV Disease Consortium.
AB  - BACKGROUND: Tuberculosis disease incidence increased sharply in New York City
      (NYC) in the late 1980s in children and adults. The relationship of tuberculosis
      disease in adults with the coincident epidemic of immunosuppression caused by HIV
      disease has been well-documented. This paper examines the relationship of
      tuberculosis and HIV in children in NYC. METHODS: Information on tuberculosis was
      collected by retrospective chart abstraction in a cohort of HIV-exposed and
      infected children enrolled in a longitudinal study of HIV. Tuberculosis cases
      were ascertained by chart review or by matching HIV-infected and -exposed
      children to NYC Tuberculosis Registry cases. NYC Tuberculosis Registry data on
      children reported from 1989 to 1995, and not reported as HIV-infected, were used
      for comparison. RESULTS: Tuberculosis disease was found in 45 (3%) of 1426 HIV
      infected children (0.61 per 100 child years of observation) and in 5 (0.5%) of
      1085 HIV-exposed uninfected children (0.2 per 100 child years). 30% of children
      were evaluated for HIV only after presenting with tuberculosis. Children with
      tuberculosis and HIV were more likely than other age-matched HIV-infected
      children to have decreased CD4+ T lymphocyte counts (66% vs. 37%, P = 0.02) and
      more likely than other NYC children with tuberculosis to have culture-confirmed
      and extrapulmonary tuberculosis. In this series 8 of 21 deaths in HIV-infected
      children with tuberculosis appeared to be related to tuberculosis. CONCLUSIONS:
      During a period of high tuberculosis incidence in NYC, 3% of HIV-infected
      children in our cohort had tuberculosis, higher than the rate in uninfected
      children born to HIV-positive mothers in the same cohort. Because of this
      association, HIV-infected children with pulmonary illness should be tested for
      tuberculosis; and all children with tuberculosis should be tested for HIV.

PMID- 10959737
TI  - Reduced lung diffusion capacity after Mycoplasma pneumoniae pneumonia.
AB  - BACKGROUND: Mycoplasma pneumoniae is a frequent but underdiagnosed cause of
      community-acquired pneumonia (CAP) in children, and appropriate macrolide
      treatment is often given late. The aim of this work was to estimate the frequency
      of pulmonary involvement in children 6 months after a clinical episode of
      Mycoplasma CAP. METHODS: We measured carbon monoxide diffusion capacity (TLCO)
      and conducted spirometric tests in 35 children without asthma or chronic lung
      disease (ages 4.5 to 15 years), 6 months and 1 year after acute CAP caused by M.
      pneumoniae (23 children), pneumococci (5 children) or viruses (7 children). Only
      11 of 23 patients with M. pneumoniae CAP required hospitalization, whereas all
      the patients with pneumococcal or viral pneumonia were admitted to hospital.
      RESULTS: Lung volumes and spirometric tests were normal for all children. TLCO
      was normal 6 months after pneumococcal or viral pneumonia (87 to 112% of expected
      values for height and sex). After acute M. pneumoniae CAP, 11 of 23 patients
      (48%) had TLCO values <80% of the expected value. The extent of change in lung
      diffusion capacity was correlated with the delay to diagnosis and treatment: TLCO
      was low in 8 of 11 patients given macrolide treatment 10 days or more after the
      onset of acute symptoms vs. only 3 of 10 patients given appropriate treatment in
      the first 10 days. TLCO was low in 7 of 7 who received macrolide therapy for <2
      weeks. TLCO had increased slightly after 1 year in the 5 patients retested after
      a new course of macrolide treatment. TLCO reached the lower normal range in 2
      patients controlled after 3 years. CONCLUSIONS: The abnormal TLCO values suggest
      that some children with Mycoplasma pneumonia have reduced pulmonary gas diffusion
      after recovery from the illness. The reduction is related to delay and short
      macrolide therapy.

PMID- 10959738
TI  - Absence of a significant interaction between a Haemophilus influenzae conjugate
      vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis
      vaccine in the same syringe and inactivated polio vaccine.
AB  - BACKGROUND: We compared the antibody response to Haemophilus influenzae type b
      capsular polysaccharide (PRP) after three doses of a diphtheria toxoid, tetanus
      toxoid and acellular pertussis vaccine (DTaP) combined with a PRP-tetanus
      conjugate (PRP-T) in infants randomized to receive oral polio vaccine (OPV) or
      inactivated polio vaccine (IPV). The polio vaccine was given separately at the
      same visit. METHODS: Three hundred fifty-six infants from pediatric practices in
      suburban Chicago and New Orleans were randomized into two groups. Group A
      received OPV at 2 and 4 months of age; Group B received IPV at 2 and 4 months of
      age. Both groups received DTaP/PRP-T at 2, 4 and 6 months of age and hepatitis B
      vaccine at 2 and 4 months of age. A serum sample was obtained before immunization
      (age 2 months) and 1 month after 3 doses of DTaP/PRP-T (age 7 months). Sera were
      assayed for antibody responses to all relevant vaccine antigens. RESULTS: No
      significant vaccine antigen interference was found when polio immunization was
      provided by IPV or OPV for anti-PRP, diphtheria, tetanus or pertussis antibodies.
      OPV recipients had a significantly higher mean antibody response to serotype 1 (P
      = 0.03) and 2 (P = 0.0001) poliovirus. CONCLUSION: Whether polio immunization was
      accomplished with IPV or OPV did not significantly influence the antibody
      responses in sera obtained at 7 months of age for anti-PRP, anti-diphtheria and
      anti-tetanus toxoid antibodies and antibodies to pertussis antigens, when
      DTaP/PRP-T was given in the primary series.

PMID- 10959739
TI  - Fluconazole for the prevention and treatment of tinea gladiatorum.
AB  - BACKGROUND: Tinea gladiatorum is a common problem in competitive wrestling. It
      impacts on a wrestler's ability to compete. Several methods have been advocated
      to prevent these infections; however, no well-designed study of pharmacologic
      prophylaxis has been conducted. METHODS: In a double blind placebo-controlled
      trial during the 1998 to 1999 regular wrestling season, wrestlers were randomized
      to receive 100 mg of fluconazole once weekly or placebo once weekly. Those not
      involved in the study were treated as a second control group. The effects of
      prophylaxis were also examined by assessing treatment of clinical infections with
      fluconazole 200 mg weekly for 4 weeks. RESULTS: There was a significantly smaller
      incidence of infection in those given fluconazole (6%) than in those receiving
      placebo (22%) and those not involved in the prophylaxis phase (18%) (P<0.05).
      There was also a significant reduction in the total number of infections in the
      fluconazole group (P<0.05). Prophylaxis with fluconazole did not impact on the
      severity of disease, if contracted, when compared with the placebo prophylaxis
      participants who contracted tinea corporis. Of 21 wrestlers with tinea infections
      and positive cultures, 14 were able to have their isolates identified as
      Trichophyton tonsurans. CONCLUSIONS: Fluconazole is effective and safe for
      primary prevention of tinea gladiatorum. We must now define when and in what
      population prophylaxis would be warranted.

PMID- 10959740
TI  - Concordance of human papillomavirus in the cervix and urine among inner city
      adolescents.
AB  - OBJECTIVES: To evaluate concordance for human papillomaviruses (HPVs) between
      cervix and urine in sexually active adolescents. METHODS: Cervical swabs and
      urine were collected from 80 adolescents in Baltimore, MD. Specimens were tested
      for 34 HPVs by PCR and for cancer-associated HPVs by Hybrid Capture (HC II) Probe
      B. Cervical vs. urine prevalence was evaluated by logistic regression with
      general estimating equations. Risk factors for prevalence and viral burden were
      evaluated by Fisher's exact and Kruskal-Wallis tests, respectively. RESULTS: HPV
      prevalence by PCR, for any HPV, was very high in the cervix (90.0%) and somewhat
      lower in urine (75.0%) (odds ratio, 1.07; 95% confidence interval 1.07 to 1.34).
      Only one adolescent was HPV-positive in urine alone. Among HPV-PCR positives at
      either or both sites, concordance was 82% for presence of any HPV and 40% for
      specific HPV types. Multiple infections were common at both sites. On an average,
      HC II viral burden (relative light unit ratio) was 9-fold higher in cervix than
      in urine (median, 47.3 vs. 4.9; P = 0.005) but correlated poorly between the two
      sites of the same individual (r = 0.14). Compared with normal adolescents, those
      with squamous intraepithelial lesions had a much higher prevalence of HPV by HC
      II in cervix (100% vs. 28.6, P<0.0001) as well as in urine (86.7% vs. 35.4%, P =
      0.002) and a significantly higher viral burden in the cervix (median, 141.8 vs.
      7.3, P = 0.0045) but not in urine (median, 22.7 vs. 4.38; P = 0.13). CONCLUSION:
      There was a very high prevalence of HPV in cervix and urine of sexually active
      adolescents. Testing urine for HPV may be useful in epidemiologic investigations
      and in monitoring of infected women.

PMID- 10959741
TI  - Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical
      manifestations and risk factors.
AB  - BACKGROUND: Little is known about the epidemiology and clinical features of
      esophageal candidiasis (EC) in pediatric AIDS. We therefore investigated the
      clinical presentation and risk factors of EC in a large prospectively monitored
      population of HIV-infected children at the National Cancer Institute. PATIENTS
      AND METHODS: We reviewed the records of all HIV-infected children (N = 448)
      followed between 1987 and 1995 for a history of esophageal candidiasis to
      characterize the epidemiology, clinical features, therapeutic interventions and
      outcome of esophageal candidiasis. To understand further the risk factors for EC
      in pediatric AIDS, we then performed a matched case-control analysis of 25
      patients for whom control cases were available. RESULTS: There were 51 episodes
      of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17
      years; median CD4, count 11/microl), representing a frequency of EC of 8.0%.
      Concurrent oropharyngeal candidiasis (OPC) was the most common clinical
      presentation of EC (94%); other signs and symptoms included odynophagia (80%),
      retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%),
      dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The
      causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic
      biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received
      treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%)
      or itraconazole (1%). A clinical response was documented in all 45 evaluable
      episodes. In 6 other cases, EC was a final event without contributing to the
      cause of death. By a conditional logistic regression model for matched data, the
      best predictor of EC was the presence of prior OPC (P<0.0001), followed by CD4
      count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P =
      0.0013). The risks associated with low CD4 count were independent of that of
      prior OPC. CONCLUSION: EC in pediatric AIDS is a debilitating infection, which
      develops in the setting of prior OPC, low CD4 counts and previous antibiotics.

PMID- 10959742
TI  - Intracranial empyema.

PMID- 10959743
TI  - Infections in burn injury.

PMID- 10959744
TI  - Research priorities and postpartum care strategies for the prevention and optimal
      management of neonatal infections in less developed countries.

PMID- 10959745
TI  - Gemella morbillorum endocarditis in a child.

PMID- 10959746
TI  - C-reactive protein in childhood non-typhi Salmonella gastroenteritis with and
      without bacteremia.

PMID- 10959747
TI  - Enterovirus 71 infections at a Canadian center.

PMID- 10959748
TI  - Immunogenicity of acellular pertussis vaccines using two vaccines for primary
      immunization.

PMID- 10959749
TI  - Hemoptysis and Epstein-Barr virus infection.

PMID- 10959750
TI  - Abiotrophia spp. brain abscess in a child with Down's syndrome.

PMID- 10959751
TI  - Cerebral tuberculosis without neurologic signs and with normal cerebrospinal
      fluid.

PMID- 10959752
TI  - Disseminated infection with varicella-zoster virus vaccine strain presenting as
      hepatitis in a child with adenosine deaminase deficiency.

PMID- 10959753
TI  - Activation of peripheral blood CD8+ T cells in adenovirus infection.

PMID- 10959754
TI  - Is acute hemorrhagic edema of infancy a complement deficiency state?

PMID- 10959755
TI  - Limitations of single point pharmacodynamic analysis.

PMID- 10959756
TI  - Is Kawasaki disease frequent in the children of parents engaged in medical work?

PMID- 10959757
TI  - From chimpanzee coryza to palivizumab: changing times for respiratory syncytial
      virus.

PMID- 10959758
TI  - Immunology of respiratory syncytial virus infection: eosinophils, cytokines,
      chemokines and asthma.

PMID- 10959759
TI  - Therapy of respiratory syncytial virus infection.

PMID- 10959760
TI  - Immunoprophylaxis of respiratory syncytial virus disease.

PMID- 10959761
TI  - Respiratory syncytial virus vaccines: recent developments.

PMID- 10959762
TI  - Next generation therapeutics. Web alert.

PMID- 10959763
TI  - The aging process: where are the drug opportunities?
AB  - New data support a role for growth hormone secretagogue receptor agonists as
      rejuvenating agents. Two enzymes critical for the formation of beta-amyloid
      plaques in Alzheimer's disease have been identified. Estrogen receptor beta
      continues to emerge as a potential drug target. The orphan nuclear receptor Nurr1
      appears to be a target for treatment of Parkinson's disease, and propargylamines
      are emerging as inhibitors of oxidative damage in neurons.

PMID- 10959764
TI  - Therapeutic approaches to Alzheimer's disease.
AB  - Several recent advances have provided new insights and possibilities in defining
      therapeutic targets for Alzheimer's disease. Of particular importance is the
      identification of the beta-secretase enzyme and the demonstration that
      immunization of a transgenic mouse model of Alzheimer's disease with Abeta(1-42)
      peptide can prevent or alleviate neuropathological features of the disease.

PMID- 10959765
TI  - New approaches to the treatment of osteoporosis.
AB  - Under physiological conditions, maintenance of skeletal mass is the result of a
      tightly coupled process of bone formation and bone resorption. Disease states,
      osteoporosis included, arise when this delicate balance is disrupted such as in
      menopause, when estrogen levels decrease dramatically corresponding with the
      cessation of ovarian function. Current therapies for the treatment of
      osteoporosis, including estrogen replacement therapy, selective estrogen receptor
      modulators and bisphosphonates, are primarily based on blunting the resorption
      component of bone homeostasis. Although selective estrogen receptor modulators
      offer bone protection without the side effects of estrogen replacement therapy,
      there are some areas of improvement for the current generation of selective
      estrogen receptor modulators; particularly in reducing their antagonistic
      properties in the central nervous system that lead to vasomotor symptoms. There
      are few therapies that are focused on increasing bone formation, but they offer
      promising avenues in which to expand the repertoire of drugs to restore bone
      mass. Selective androgen receptor modulators, parathyroid hormone analogs,
      oxytocin analogs and statins, all with improved pharmacological properties in
      bone, are among the potential approaches to eliciting anabolic effects in the
      skeleton.

PMID- 10959766
TI  - New advances in the discovery of thrombin and factor Xa inhibitors.
AB  - The search for the ideal anticoagulant has spanned decades and has resulted in
      several strategies including the clinical use of heparin, low molecular weight
      heparins, and the vitamin K antagonist warfarin. Over the past five years, many
      groups have reported preclinical results with direct-acting thrombin inhibitors
      and several of these are now moving into clinical trials. In addition, many
      groups have disclosed the discovery of potent, orally bioavailable factor Xa
      inhibitors. Several of these compounds are now in early clinical trials and the
      results are forthcoming.

PMID- 10959767
TI  - Bradykinin antagonists: new opportunities.
AB  - The pro-inflammatory, pain producing, and cardiovascular effects of bradykinin B2
      receptor activation are well characterized. Bradykinin B1 receptors also produce
      inflammation and pain. Therefore, antagonists are expected to be anti
      inflammatory/analgesic drugs. Other exploitable clinical opportunities may exist.
      The newly discovered non-peptide B2 receptor antagonists and the equivalent B1
      receptor pharmacological agents, which are in the pipeline, are suitable
      preclinical tools to properly evaluate potential utilities.

PMID- 10959768
TI  - Asthma: where beyond steroids?
AB  - The prevalence of asthma is increasing dramatically despite major changes in
      monitoring and treatment of this disease. Currently available bronchodilators and
      anti-inflammatory drugs are effective in most patients, although these can have
      side effects and are mainly symptomatic. Many drugs are now in development for
      the treatment of asthma. Most of these new therapies are aimed at inhibition of
      the inflammatory components, with better safety profiles than steroids.

PMID- 10959769
TI  - Chronic obstructive pulmonary disease: emerging therapies.
AB  - Despite the high prevalence of and mortality from chronic obstructive pulmonary
      disease, extensive research on the underlying pathophysiology and specific
      therapeutics for this disease is, relatively, in its infancy. Several novel
      molecular targets are being investigated as potential treatments for the disease.
      The most exciting new class of compounds is the phosphodiesterase 4 inhibitors;
      Ariflo (SB 207499)-a member of this class, and the most advanced in development
      (Phase III)-was reported recently to have significant clinical efficacy in
      patients with chronic obstructive pulmonary disease. Phosphodiesterase 4
      inhibitors, such as Ariflo, possibly represent the most important advance in
      pulmonary medicine in recent years.

PMID- 10959770
TI  - The chemokine/chemokine-receptor family: potential and progress for therapeutic
      intervention.
AB  - The chemokines are a large superfamily of chemotactic cytokines that are utilized
      to direct the trafficking and migration of leukocytes within the immune system.
      The chemokines mediate their activity through a large family of G-protein-coupled
      receptors, and thus are highly tractable as therapeutic targets. Exciting
      advances have been made in the field within the past year, not the least of which
      is the disclosure of potent antagonists of several chemokine receptors. Several
      CCR5 antagonists have demonstrated potent antiviral activity and may represent
      novel therapeutic agents for the treatment of AIDS. In addition, new biological
      insights have been gained from the demonstration that the targeting of cells to
      inflammatory sites is tissue specific, such that different chemokine/chemokine
      receptor pairs are utilized in recruitment of T-lymphocytes to the skin and to
      the intestine. Also, utilization of neutralizing antibodies to the CXCR3 ligand
      Mig in murine allograft transplantation models has demonstrated the importance of
      CXCR3 in orchestrating T-cell-mediated tissue rejection.

PMID- 10959771
TI  - Gastrointestinal functional bowel disorders: new therapies.
AB  - Present therapies for functional gastrointestinal disorders are symptomatic and
      mainly treat altered bowel habits. New therapies are focused on nerve-gut
      communication dysfunction: 5-HT3 antagonists and 5-HT4 agonists have demonstrated
      activity in clinical trials. Promising targets for upper gut dysmotility drugs
      are motilin and cholecystokinin A receptors. Tachykinins, calcitonin gene-related
      peptide or glutamate antagonists are the most relevant candidates for visceral
      pain.

PMID- 10959772
TI  - New approaches in the treatment of bacterial infections.
AB  - Recently, several new drugs for the treatment of bacterial infections have been
      developed. Quinupristin/dalfopristin, moxifloxacin and gatifloxacin have been
      approved throughout the world for clinical use. Levofloxacin has been approved
      for the treatment of community-acquired pneumonia caused by penicillin-resistant
      Streptococcus pnuemoniae. The Food and Drug Administration has approved linezolid
      for clinical use, and new drug applications for gemifloxacin and telithromycin
      were filed. Other new targets have surfaced in the quest for novel antibacterial
      agents.

PMID- 10959773
TI  - New advances in pharmacogenomics.
AB  - In the years to come, pharmacogenomics will make an impact on the development of
      new drugs. Numerous publications have shown that gene polymorphism can influence
      drug toxicity and/or efficacy. In order to improve current applications of
      pharmacogenomics, some technical limitations regarding marker generation,
      genotyping and biostatistical analysis are being overcome.

PMID- 10959774
TI  - High-throughput screening: new technology for the 21st century.
AB  - New technologies in high-throughput screening have significantly increased
      throughput and reduced assay volumes. Key advances over the past few years
      include new fluorescence methods, detection platforms and liquid-handling
      technologies. Screening 100,000 samples per day in miniaturized assay volumes
      will soon become routine. Furthermore, new technologies are now being applied to
      information-rich cell-based assays, and this is beginning to remove one of the
      key bottlenecks downstream from primary screening.

PMID- 10959775
TI  - Obesity: an epidemic in need of therapeutics.
AB  - Recent developments in the quest for control of human obesity include the
      discovery of hormones, neuropeptides, receptors and transcription factors
      involved in feeding behavior, metabolic rate and adipocyte development. As a
      result, obesity research is quickly developing a level of sophistication that is
      expected to yield new treatment approaches. Even though newly approved clinical
      interventions are being tested in the market place, the obesity epidemic
      continues to face numerous unmet clinical needs and awaits the development and
      implementation of safe and highly effective pharmacotherapy.

PMID- 10959776
TI  - New approaches in the treatment of type 2 diabetes.
AB  - Type 2 diabetes is a chronic metabolic derangement that results from defects in
      both insulin action and secretion. New thiazolidinedione insulin sensitizers have
      been recently launched. New approaches with mechanisms different from current
      therapies are being explored, including novel ligands of peroxisome proliferator
      activated receptor, glucagon receptor antagonists, dipeptidyl peptidase IV
      inhibitors, and insulin receptor activators.

PMID- 10959777
TI  - Transdermal iontophoresis revisited.
AB  - Iontophoresis evolved as a transdermal enhancement technique in the 20th century,
      primarily for the delivery of large and charged molecules. Significant
      achievements have been made in the understanding of underlying mechanisms of
      iontophoresis and these have contributed to the rational development of
      iontophoretic delivery systems. The major challenges in this area are the
      development of portable, cost effective devices and suitable semi-solid
      formulations that are compatible with the device and the skin. Some of the
      obstacles in transdermal iontophoresis can be overcome by combining iontophoresis
      with other physical and chemical enhancement techniques for the delivery of
      macromolecules. Iontophoresis also offers an avenue for extracting information
      from the body through the use of reverse iontophoresis, which has potential
      application in diagnosis and monitoring. The current research is focussed towards
      resolving the skin toxicity issues and other problems in order to make this
      technology a commercial reality.

PMID- 10959778
TI  - Plasma lipid and blood glucose levels in patients with destructive periodontal
      disease.
AB  - Hyperlipidaemia and hyperglycaemia are major risk factors for cardiovascular
      disease. In recent years, some evidence has been presented that periodontal
      disease is associated with an increased risk of cardiovascular disease. To
      further elucidate this association, we have studied standard blood chemistry
      variables known as risk markers for cardiovascular disease in periodontally
      diseased and healthy subjects. We have measured levels of plasma lipids and
      fasting blood glucose in 39 subjects with moderate periodontal disease (age 50-60
      years) and compared the results with those obtained in 40 age- and sex-matched
      controls. Both groups were systemically healthy according to their medical
      history. Total cholesterol, low density lipoprotein cholesterol and triglycerides
      were significantly higher in periodontally diseased subjects by about 8%
      (p<0.03), 13% (p<0.003) and 39% (p<0.001), respectively, when compared to
      controls. Although subjects with diabetes were excluded from the study, we found
      significantly higher blood glucose levels in the patient than in the control
      group (85 +/- 25 versus 73 +/- 17 mg/dl; p<0.02). There was also a significantly
      higher frequency of pathological plasma lipid profiles in the patient than in the
      control group. The results indicate that hyperlipaemia and pre-diabetes may be
      associated with periodontal disease in systemically healthy subjects. These data
      do not allow us to decide, whether periodontal disease causes an increase in
      hyperlipaemia and in a prediabetic state or whether periodontal disease and
      cardiovascular disease share hyperlipidaemia and the prediabetic state as common
      risk factors.

PMID- 10959779
TI  - Testing the efficacy of plaque removal of a prototype brush head for a powered
      toothbrush.
AB  - BACKGROUND/AIMS: The principal aim of the study was to compare the efficacy of a
      powered toothbrush (PTB) prototype (B) brush head in removing dental plaque to
      the relative efficacy of a marketed model (A). METHOD: A 12-week, 2-group, 2
      treatment, double-blind trial of 2, two-brush heads (with the same power unit)
      recruited 62 volunteers (18-25 years) who were non-clinical university students.
      After a screening visit, 31 subjects were allocated to each of groups A and B at
      baseline with stratification according to gender and plaque index. After 48 h of
      plaque growth, subjects underwent a timed and supervised brushing episode with
      the allocated PTB (visit 1). Subjects then used the PTBs at home for 12 days
      before being recalled (visit 2) and asked again to abstain from all oral hygiene
      measures for 48 h. Supervised brushing was repeated (visit 3) before the subjects
      were dismissed for a further 10-week, unsupervised period of home use of the
      PTBs. The sequence of visits (2 and 3) was then repeated at visits 4 and 5.
      RESULTS: The sole outcome variable was plaque which was scored at all visits
      using the modified Quigley & Hein Index (PI) at full mouth (FM), interproximal
      (IP) and smooth surfaces (S). At visits 1, 3 and 5, the PI was recorded both
      before and after supervised brushing. There were no significant differences in PI
      between the brushing groups at baseline, visit 1, visit 2 or visit 5 (2 sided t
      test). At visit 3, the prototype achieved significantly lower PIs than the
      marketed PTB brush head for IP (and FM) surfaces, this difference was most
      apparent on posterior tooth surfaces. For within-group changes, PIs at visit 2
      were significantly lower than those at baseline (paired t-test), an observation
      which may be attributable to the improved cleaning and 'novelty effect' of a PTB.
      The PIs at visit 5 were significantly higher than the baseline values (paired t
      test) and this may be accountable to an element of Hawthorne effect and/or, a
      fall off in compliance over the entire 12 weeks. CONCLUSION: We conclude that
      this in vivo model is appropriate for testing the efficacy of PTB prototypes but
      only over a 2-week period, as the inter-group differences were not maintained
      over the full 12 weeks of the trial.

PMID- 10959780
TI  - Prevalence of Actinobacillus actinomycetemcomitans and clinical conditions in
      children and adolescents from rural and urban areas of central Italy.
AB  - BACKGROUND: The aim of this study was to report on the prevalence of
      Actinobacillus actinomycetemcomitans (Aa) and the periodontal clinical conditions
      in children and adolescents from a rural area of central Italy compared with the
      ones from an urban area of the same region. METHOD: The study population
      consisted of 780 systemically healthy children, aged 6-14 years inhabiting the
      county of Chieti. 505 children attended 3 primary and 2 secondary schools from a
      rural area whereas 275 individuals attended 1 primary and 1 secondary school from
      the city of Chieti. The 2 provincial areas present a great difference in
      socioeconomic level and cultural background. Clinical examination consisted of
      recording the % of gingival sites positive for the presence of plaque (P1+),
      bleeding on probing (BOP+), mean probing depth (PD) from each primary or
      permanent tooth fully erupted in the oral cavity. Loss of periodontal attachment
      (AL+) was evaluated only in interproximal sites. AL+ subjects were distinguished
      in juvenile periodontitis (JP) prepubertal periodontis and early periodontitis
      (EP) patients. 8 gingival sites were microbiologically sampled in each subject
      and cultured, after pooling, for the presence of Aa. RESULTS: 30.3% of rural
      subjects, were positive for the presence of Aa, the difference from urban
      children (16%) being statistically significant (p=0.01) irrespective of gender
      and age. Aa showed a significantly (p=0.006) higher mean proportion in
      subgingival plaque samples from rural children (0.13% versus 0.02%). Loss of
      periodontal attachment in at least one site was found in 18 rural children
      (3.56%) (3 JP; 15 EP) and 2 urban girls (0.72%)(1 JP; 1 EP). No significant
      differences for AL were observed within the rural group according to the gender
      and age differentiation. In the urban group, both AL+ subjects were Aa+, while
      among children from rural areas all 3 JP and 13 EP subjects were Aa+. Rural
      subjects evidenced significantly worse clinical parameters with respect to urban
      children (% PI+ sites: p=0.000; % BOP+ sites: p=0.010; mean PD: p=0.000.) The
      relative risk for AL+ sites was significantly greater (2.42) in rural subjects
      harboring Aa in subgingival plaque. Similarly, the presence of Aa in subgingival
      plaque was related to a greater risk of more than 50% of BOP+ gingival sites in
      both rural and urban subjects (1.45 and 8.40, respectively). CONCLUSIONS: Results
      of this study suggest that Aa colonization in children and adolescents from
      central Italy is affected by socioeconomic and cultural factors; these factors
      also affect the periodontal condition of the subjects.

PMID- 10959782
TI  - Alveolar bone loss in type 1 diabetic subjects.
AB  - AIM, BACKGROUND: The aim of this study was to assess the degree of marginal
      alveolar bone loss in a group of young subjects with type 1 diabetes mellitus
      (DM) (n=35, age range 24-36 years) and age-matched non-diabetic control subjects
      (n=10). METHOD: The diabetic group was divided into 3 subgroups (D1, D2, D3)
      according to the severity of the diabetic state. The level of alveolar bone was
      measured on panoramic radiographs of maxillary and mandibular molars as the % of
      the distance between the cemento-enamel junction (CEJ) and the bone crest along
      the total length of the root. All mesial and distal sites with a distance of >
      15% (BL>15%) were picked, and calculations were performed using the individual %s
      of sites with BL> 15%. RESULTS: Based on the present findings, we conclude that
      type 1 DM has a modifying effect on marginal loss of alveolar bone. A clear trend
      towards increased marginal bone loss was seen in the subjects with complicated DM
      (D3). The subjects with good metabolic control and no complications of DM (D1)
      are no more susceptible to marginal bone loss than non-diabetic controls of the
      same age. CONCLUSIONS: The present findings confirm our previous results on
      increased loss of periodontal support in subjects with complicated DM already at
      an early age.

PMID- 10959781
TI  - Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult
      periodontitis.
AB  - The reported therapeutic benefits of nonsteroidal anti-inflammatory drugs
      (NSAIDs) in slowing periodontal disease progression appear intimately linked to
      the effective inhibition of local prostaglandin synthesis. This randomized,
      partially double-blind, controlled trial was conducted to evaluate the
      pharmacodynamic effects of the NSAID, ketoprofen (KTP), on gingival crevicular
      fluid (GCF) prostanoids. 42 subjects, ages 35-57 years, with moderate to advanced
      adult periodontitis were recruited and monitored for 22 days. On day 1, subjects
      were randomized for 1 of 5 treatments: i) 0.5% KTP gel; ii) 1.0% KTP gel; iii)
      1.0% KTP alternate gel; iv) 2.0% KTP gel; v) 25 mg KTP capsule (positive
      control). Subjects applied 1 ml of gel topically to their gingiva or administered
      one capsule p.o., b.i.d. for 14.5 days. GCF samples were collected from
      posterior, interproximal sites on days 1 (pre-dosing; 1, 2, 3, 6 h), 8 (pre
      dosing; 2 h), 15 (pre-dosing; 2 h) and 22 (post-treatment). GCF levels of
      prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were determined using RIA, and
      expressed in ng/ml and % reduction from baseline (%Effect). Neither a significant
      difference among groups nor a dose response in % effect for either prostanoid was
      evident, both overall and among cohorts with elevated baseline mediator levels
      ([PGE2]>34 ng/ml; [LTB4]>300 ng/ml). When data were combined from all groups,
      significant (p<0.01) % reductions in GCF PGE2 were noted at 1 and 2 h post-dosing
      (29% and 24% respectively). In comparing topical versus systemic formulations,
      all topical formulations were as equipotent as systemic dosing in altering local
      prostaglandin levels despite lower KTP exposures with gel treatments. These data
      indicate that both topical and systemic KTP therapies pharmacodynamically reduce
      GCF PGE2 levels in adult periodontitis subjects, allowing for potential
      inhibition of disease progression.

PMID- 10959783
TI  - Expression of intracellular elastase activity in peripheral neutrophils from
      patients with adult periodontitis.
AB  - This study aimed to investigate whether circulating neutrophils from patients
      with periodontitis contain more catalytically active elastase than neutrophils
      from healthy controls. The amount of IL-1beta in these cells was also analyzed
      and the correlation with elastase activity was tested. The periodontitis group
      consisted of 15 subjects with marked periodontal destruction. The healthy control
      group consisted of 15 subjects with no clinical signs of periodontal destruction.
      The elastase activity and the IL-1beta content in the cells were measured with
      flow cytometry using a specific substrate and antibodies, respectively. The
      plasma concentration of IL-1beta and the total content of antigenic elastase in
      the crushed cells were measured with an ELISA. The elastase activity per
      neutrophil was significantly higher in the patients than in the controls, while
      the total antigenic elastase content did not differ. The % of cells positively
      stained for IL- 1beta was somewhat higher in the patient group. Significantly
      higher amounts of IL-1beta per sample, estimated by multiplying the % of stained
      cell with the amount of staining per cell, were found in the patient group. A
      significant correlation between IL-Ibeta and elastase activity was noted in the
      patient group (R=0.6, p=0.001), but not in the control group. In conclusion,
      peripheral neutrophils from patients with adult periodontitis express more active
      elastase and total amounts of IL-1. The similar amounts of antigenic elastase
      suggests that this higher activity is possibly due to some kind of
      priming/activation already in the circulation.

PMID- 10959784
TI  - The role of chlorhexidine in the one-stage full-mouth disinfection treatment of
      patients with advanced adult periodontitis. Long-term clinical and
      microbiological observations.
AB  - BACKGROUND/AIMS: Recent studies reported significant additional clinical and
      microbiological improvements when severe adult periodontitis was treated by means
      of a "one-stage full-mouth" disinfection instead of a standard treatment strategy
      with consecutive root planings quadrant per quadrant. The one stage full-mouth
      disinfection procedure involves scaling and root planing of all pockets within 24
      h in combination with an extensive application of chlorhexidine to all intra-oral
      niches such as periodontal pockets, tongue dorsum, tonsils (chairside, and at
      home for 2 months). This study aims to examine the relative importance of the use
      of chlorhexidine in the one stage full-mouth disinfection protocol. METHODS:
      Therefore, 3 groups of 12 patients each with advanced periodontitis were
      followed, both from a clinical and microbiological point of view, over a period
      of 8 months. The patients from the control group were scaled and root planed,
      quadrant per quadrant. at two-week intervals. The 2 other groups underwent a one
      stage full-mouth scaling and root planing (all pockets within 24 h) with (Fdis)
      or without (FRp=full-mouth root planing) the adjunctive use of chlorhexidine. At
      baseline and after 1, 2, 4 and 8 months, the following clinical parameters were
      recorded: plaque and gingivitis indices, probing depth, bleeding on probing and
      clinical attachment level. Microbiological samples were taken from different
      intra-oral niches (tongue, mucosa, saliva and pooled samples from single- and
      multi-rooted teeth). The samples were cultured on selective and non-selective
      media in order to evaluate the number of CFU/ml for the key-periodontopathogens.
      At baseline, an anonymous questionnaire was given to the patients to record the
      perception of each treatment (post operative pain, fever, swelling etc.).
      RESULTS: All 3 treatment strategies resulted in significant improvements for all
      clinical parameters, but the Fdis and FRp patients reacted always significantly
      more favourably than the control group, with an additional probing depth
      reduction of +/- 1.5 mm and an additional gain in attachment of +/- 2 mm (for
      pockets > or = 7 mm). Also from a microbiological point of view both the FRp and
      Fdis patients showed additional improvements when compared to the control group,
      as well in the reduction of spirochetes and motile organisms as in the number of
      CFU/ml of the key-pathogens, especially when the subgingival plaque samples were
      considered. The differences between FRp and Fdis patients were negligible.
      CONCLUSIONS: These findings suggest that the benefits of a "one-stage full-mouth
      disinfection" in the treatment of patients suffering from severe adult
      periodontitis probably results from the full-mouth scaling and root planing
      within 24 h rather than the beneficial effect of chlorhexidine. The raise in body
      temperature the second day after the full-mouth scaling and root planing seems to
      indicate a Shwartzman reaction.

PMID- 10959785
TI  - Effect of subgingival scaling during supportive therapy.
AB  - BACKGROUND, AIMS: This prospective study was designed to investigate the role of
      root debridement at 3 month intervals for patients with periodontitis whose
      disease had persisted following the completion of conventional periodontal
      treatment. METHODS: 39 maintenance patients with at least 4 pockets at least 4 mm
      deep were assigned to coronal scaling (CS) and subgingival scaling (SS) groups.
      Probing depths (PD), bleeding on probing (BOP) and relative attachment levels
      (RAL) were recorded at all eligible sites at baseline and 3, 6, 9 and 12 months
      later. Plaque index scores were recorded at the 12-month visit. At every visit,
      following data collection, both groups received a coronal scaling and the SS
      group, in addition, received a thorough subgingival debridement. In the CS group,
      subgingival debridement was performed only for 'loser' sites which inhibited loss
      of attachment > or = 2 mm relative to baseline values. Due to low compliance,
      only 31 patients completed the study. Thus, data analyses were carried out for
      130 sites in 17 CS group patients and 146 sites in 14 SS group patients. RESULTS:
      During the course of the study, 21 loser sites were identified in each group, but
      the difference in proportion of loser sites between groups was not significant.
      Furthermore, although there was a trend toward PD reduction in both groups
      throughout the study, mean PD, RAL and BOP values were not significantly
      different from baseline values at any time point, and there were no significant
      differences between groups with respect to these variables. Mean plaque scores
      measured at the 12-month visit revealed no significant differences between
      groups. CONCLUSION: These findings call into question the value of performing
      repeated subgingival scaling at 3-month intervals for patients with persistent
      disease.

PMID- 10959786
TI  - Prevalence of Bacteroides forsythus, Porphyromonas gingivalis and Actinobacillus
      actinomycetemcomitans in subgingival microflora of Japanese patients with adult
      and rapidly progressive periodontitis.
AB  - BACKGROUND, AIMS: This study investigated the prevalence of Bacteroides
      forsythus, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans
      among various periodontitis patients and healthy individuals in Japan, and
      correlated it with clinical parameters. METHOD: Subgingival plaque samples were
      collected from 21 patients with adult periodontitis (AP), 8 with rapidly
      progressive periodontitis (RPP) and 15 healthy individuals. RESULTS: The
      frequency detected in culture was as follows: B. forsythus was found in 47.6% of
      AP sites and in 37.5% of RPP sites. P. gingivalis was identified in 64.3% of AP
      and 59.4% of RPP sites. A. actinomycetemcomitans was detected in 4.8% of AP and
      3.1% of RPP sites. The 3 species were detected in only 2 of the healthy
      individuals. The proportion of B. forsythus in the total microflora in culture
      was 0.07% in the healthy group, 4.1% in AP and 2.4% in RPP. The proportions of P.
      gingivalis were 0% in the healthy group, 18.8% in AP and 16.2% in RPP. The
      proportion of A. actinomycetemcomitans was very low in all 3 groups. A DNA probe
      detected B. forsythus in 78.6% of AP and 65.6% of RPP sites, as well as
      P.gingivalis in 58.3% of AP and 59.4% of RPP sites. A. actinomycetemcomitans was
      detected in only 1.2% of AP sites. The 3 species were undetectable in the healthy
      group. CONCLUSIONS: The prevalence and the proportion of B. forsythus and P.
      gingivalis were significantly correlated with clinical parameters, suggesting
      that B. forsythus and P. gingivalis are closely related to AP and RPP in the
      Japanese population.

PMID- 10959788
TI  - The role of time in reducing gingival overgrowth in heart-transplanted patients
      following cyclosporin therapy.
AB  - BACKGROUND, AIMS: In a previous cross-sectional study, the relevant role of time
      in reducing gingival overgrowth (GO) in heart-transplanted patients undergoing
      Cyclosporin A (CsA) therapy was hypothesized to explain the inverse relationship
      between GO and months since the graft. METHODS: In the present study, the
      relationship between GO and time was investigated prospectively in a group of 21
      heart transplanted patients who have been regularly followed up to 48 months.
      RESULTS: 6 months after beginning CsA therapy (1st appointment), 7 out of 21
      patients (33%) had clinical GO as confirmed by a hyperplastic index (HI) >30.
      There was no significant difference between these values with respect to those
      detected during the 2nd appointment at 9 months. At this time, all patients
      underwent a regular oral hygiene program. Gingival and plaque indices
      significantly decreased at the 3rd appointment (12 months) both in the group of
      responders and in the group of non-responders and remained significantly
      unchanged with time; HI significantly decreased with time only in the group of
      responders, the decrease becoming significant 36 months after heart
      transplantation. As a consequence, the number of responders decreased from 7 at
      the 1st appointment to 5 after 12 months, 4 after 24 months, 2 after 36 months
      following heart transplantation. CONCLUSION: The results suggest that GO
      necessarily develops in responders within 6 months from heart transplantation and
      in most subjects may be a time-related side-effect probably due to a progressive
      reduction in the sensitivity of the periodontum to CsA.

PMID- 10959787
TI  - Comparison of treatments of infrabony defects with enamel matrix derivative,
      guided tissue regeneration with a nonresorbable membrane and Widman modified
      flap. A pilot study.
AB  - BACKGROUND, AIMS: The purpose of the present study was to compare the efficacy of
      3 different surgical procedures in the treatment of infrabony defects: guided
      tissue regeneration (GTR) with non-resorbable membranes, Widman modified flap
      (WMF) and enamel matrix derivative (EMD). METHOD: 30 patients with an infrabony
      component > or = 4 mm were selected. 10 were treated with expanded
      polytetrafluorethylene (ePTFE (Gore - Tex W. L. Gore and Associates, Flagstaff,
      AZ, USA)) membranes, 10 with WMF and 10 with enamel matrix derivatives (Emdogain
      (U Biora AB Malm, Sweden)). The efficacy of each treatment modality was
      investigated through regression analysis. Probing attachment level (PAL) gain,
      probing depth (PD) reduction and gingival recession (REC) variation were
      analyzed. RESULTS: Both Emdogain (enamel matrix derivative) and ePTFE treatment
      show significant better results as compared to the WMF procedure in which there
      were no significant changes in PAL gain and PD reduction at baseline and 1 year
      after surgery. CONCLUSIONS: Results from our analysis suggest that there is no
      statistically significant difference in PAL gain between GTR and EMD. The
      clinical outcomes of this pilot study may be of little significance, considering
      the small number of patients, but it has provided an important base for a
      controlled clinical trial (with a larger number of patients) which is currently
      in progress.

PMID- 10959789
TI  - Rehabilitation of a periodontal patient with rapidly progressing marginal
      alveolar bone loss: 1-year follow-up.
AB  - BACKGROUND: The present case report describes a 1-year follow-up of functional
      rehabilitation of a young periodontal patient with severely advanced, rapidly
      progressing marginal bone loss treated by using a new splinting material, i.e.,
      glass fiber-reinforced composite (FRC). Apart from one single tooth, the young
      man had retained all his natural teeth. TREATMENT: Periodontal treatment was
      based on cleaning and root planing enabled by partial-thickness-flap operations.
      This method was selected to avoid further damage to the remaining alveolar bone.
      After healing for 6 months, a cavity retained internal FRC splint was constructed
      and 1 missing lower molar was replaced by an inlay-retained FRC resin-bonded
      fixed partial denture (FPD). A 12 months follow-up period revealed a healthy
      periodontium and good functional and esthetic results. CONCLUSIONS: The new
      material allows the use of periodontal treatment methods instead of prosthetic
      alternatives, which until now have been a more generally used approach in the
      treatment of severely advanced periodontal cases. Internal fiber-reinforced
      composite splinting being affordable for the patient, easy for the clinician to
      construct and giving good esthetic and functional results, suggests that the
      method may be a valuable aid in periodontal treatment.

PMID- 10959790
TI  - Species differences in acrylonitrile metabolism and toxicity between experimental
      animals and humans based on observations in human accidental poisonings.
AB  - The high acute toxicity of acrylonitrile may be a result of its intrinsic
      biological reactivity or of its metabolite cyanide. Intravenous N-acetylcysteine
      has been recommended for treatment of accidental intoxications in acrylonitrile
      workers, but such recommendations vary internationally. Acrylonitrile is
      metabolized in humans and experimental animals via two competing pathways; the
      glutathione-dependent pathway is considered to represent an avenue of
      detoxication whilst the oxidative pathway leads to a genotoxic epoxide,
      cyanoethylene oxide, and to elimination of cyanide. Cases of acute acrylonitrile
      overexposure or intoxication have occurred within persons having industrial
      contact with acrylonitrile; the route of exposure was by inhalation and/or by
      skin contact. The combined observations lead to the conclusion of a much higher
      impact of the oxidative metabolism of acrylonitrile in humans than in rodents.
      This is confirmed by differences in the clinical picture of acute life
      threatening intoxications in both species, as well as by differential efficacies
      of antidotes. A combination of N-acetylcysteine with sodium thiosulfate seems an
      appropriate measure for antidote therapy of acute acrylonitrile intoxications.
      Clinical observations also highlight the practical importance of human individual
      susceptibility differences. Furthermore, differential adduct monitoring,
      assessing protein adducts with different rates of decay, enables the development
      of more elaborated biological monitoring strategies for the surveillance of
      workers with potential acrylonitrile contact.

PMID- 10959792
TI  - Effects of protein-deficient nutrition during rat pregnancy and development on
      developmental hindlimb crossing due to methylmercury intoxication.
AB  - Pregnant rats were fed either a control (20% protein) or low (3.5%) protein diet
      during gestation and lactation. The pups were separated from their mothers on
      postnatal day 21, and were given the same diet as their corresponding mothers.
      The groups of pups from each diet group were treated on either postnatal day 21
      or postnatal day 60 with 7.5 mg methylmercury chloride (MeHgCl) per kg b.w. once
      daily by gavage for 10 consecutive days, and the development of ataxia (hind-limb
      crossing) was monitored. The offspring from mothers on the protein-deficient diet
      were found to be more sensitive to MeHg-induced ataxia than those on the protein
      sufficient diet. The former accumulated more mercury in different brain regions
      than the latter. The rates of protein synthesis in different brain regions of the
      offspring fed the protein-deficient diet were significantly reduced compared with
      the rates in those fed the protein-sufficient diet. However, MeHg treatment did
      not significantly modify the rates of such protein synthesis further in protein
      deficient rats. Thus, a significantly much higher inhibition of the intrinsic
      rates of protein synthesis in different brain regions due to severe protein
      deficiency, as observed in this study, may be partly responsible for the
      increased susceptibility of developing rats fed a protein-deficient diet to MeHg
      induced ataxia, or hindlimb crossing, although other factor(s) might also be
      involved.

PMID- 10959791
TI  - Competition between copper and silver in Fischer rats with a normal copper
      metabolism and in Long-Evans Cinnamon rats with an abnormal copper metabolism.
AB  - Long-Evans Cinnamon (LEC) rats inherently lacking in serum ceruloplasmin (CP)
      activity and biliary Cu excretion were established from a closed colony of Long
      Evans rats. These deficiencies, linked to a dysfunction of P-type ATPase,
      stimulate deposition of Cu and then of Cu metallothionein (MT) in the liver. Male
      LEC and Fischer rats were injected subcutaneously with Ag (AgNO3), which is an
      antagonist to Cu. They were operated on 24 h after the injection while under
      anesthesia. Total uptake of Ag into the liver was not stimulated, but its uptake
      into the MT fraction increased significantly in the LEC rats. Ag injection
      notably decreased the activity of serum CP in the Fischer rats, but not in the
      LEC rats. The decrease was accompanied by a reduction of serum Cu. In Fischer rat
      serum treated with Ag, Ag was detected mainly in the albumin region and partly in
      the CP fraction. In LEC rat serum, however, the Ag concentration was about 1/20
      of that in the Fischer rats, and Ag was not detected in the CP fraction. Ag
      injection decreased the biliary excretion of Cu in the Fischer rats (0.183-0.052
      microg Cu/20 min sampling), but not in the LEC rats (0.014-0.014 microg Cu/20 min
      sampling). On the other hand, biliary excretion of Ag was much greater in the
      Fischer rats (1.25 microg Ag/20 min) than in the LEC rats (0.04 microg Ag/20
      min). Our results suggest that uptake of Ag into the liver is not dependent on
      the hepatic Cu content and status, but that biliary excretion of Ag from the
      liver is affected by these. Hepatic MT is not a transporter of hepatobiliary
      excretion of Cu and Ag. It seems likely that, unlike Cu excretion, Ag is excreted
      by not only the CP route but also by another route into the serum. Ag may compete
      with Cu in the uptake into CP (conversion of apo-CP to holo-CP).

PMID- 10959793
TI  - Effect of diet on haemoglobin adducts from 4-aminobiphenyl in rats.
AB  - High levels of haemoglobin (Hb) adducts from 4-aminobiphenyl (4-ABP), a proven
      human carcinogen, have been reported in untreated animals from different
      laboratories fed various commercial standard diets. Therefore, the impact of
      dietary modifications on 4-ABP Hb adducts was investigated. Female Sprague-Dawley
      rats were fed a regular standard diet or three different test diets for 4 weeks.
      4-ABP Hb adducts were significantly lower in rats on vegetable-based test diets
      #2 (596+/-183 pg/g Hb, P = 0.028) and #3 (537+/-48 pg/g Hb, P = 0.009) compared
      with controls (974+/-154 pg/g Hb). Cereal-based test diet #1 (1080+/-388 pg/g Hb)
      had no influence on the basal Hb adduct levels determined before the start of the
      experiment (1054+/-163 pg/g Hb). In conclusion, the body burden of rats with 4
      ABP could be significantly reduced by dietary modifications.

PMID- 10959794
TI  - Biomonitoring of exposure to lewisite based on adducts to haemoglobin.
AB  - The development of a procedure for retrospective detection and quantitation of
      exposure to the arsenical dichloro(2-chlorovinyl)arsine (lewisite; L1) has been
      initiated. Upon incubation of human blood with [14C]L1 (20 nM-0.2 mM) in vitro,
      more than 90% of the total radioactivity was found in the erythrocytes and 25-50%
      of the radioactivity becomes associated with globin. Evidence was obtained for
      the presence of several binding sites. One type of binding was identified as L1
      induced crosslinking of cysteine residues 93 and 112 of the beta-globin chain. A
      method was developed for extraction of bound and unbound 2-chlorovinylarsonous
      acid (CVAA), a major metabolite of L1, from whole blood after treatment with 2,3
      dimercapto-1-propanol (BAL). Subsequent to derivatization with heptafluorobutyryl
      imidazole, the CVAA-BAL derivative could be analysed at a 40-fmol level by means
      of gas chromatography-mass spectroscopy (GC-MS) under electron impact conditions.
      With this procedure, in vitro exposure of human blood to 1 nM L1 could be
      determined. The same procedure was applied to the analysis of human urine samples
      spiked with CVAA. In vivo exposure of guinea pigs could be established at least
      240 h after subcutaneous administration of the agent (0.25 mg/kg) by the
      determination of bound and unbound CVAA in the blood. In the urine of these
      animals, CVAA could be detected for 12 h after exposure.

PMID- 10959795
TI  - Quantification of individual glutathione S-transferase isozymes in hepatic and
      pulmonary tissues of naphthalene-tolerant mice.
AB  - Acute exposure to naphthalene produces severe bronchiolar epithelial cell
      necrosis in mice, whereas subchronic exposure to naphthalene (200 mg/kg/7 days)
      fails to produce epithelial necrosis and renders the animals tolerant to
      subsequent challenge doses of naphthalene. Mechanisms responsible for the
      development of tolerance have not been delineated. The few studies exploring
      naphthalene tolerance focus on expression of microsomal enzymes and have yet to
      delve into expression of the hepatic detoxification enzymes such as glutathione S
      transferases (GSTs; EC 2.5.1.18). Glutathione conjugation catalyzed by GSTs
      accounts for one of the two primary routes of naphthalene detoxification. In this
      study, we rigorously quantify levels of individual GST isozymes expressed within
      the livers and lungs of mice with acquired tolerance to naphthalene. Subchronic
      exposure to naphthalene increases the abundance of some hepatic GSTs to levels as
      much as 68% greater than controls. Naphthalene-tolerant mice displayed increases
      in mGSTM1 (51%), mGSTM2 (58%), and mGSTP1 (66%), whereas no significant
      difference in mGSTA3 was observed between exposed and control mice. Extracts of
      pulmonary tissues from naphthalene-tolerant mice showed minor increases in levels
      of mGSTP1 (7%) and Peak 8 isozyme (27%) and decreases in levels of mGSTM1 (31%),
      mGSTM2 (17%), and mGSTA3 (8%). The total enzymatic activity for the conjugation
      of 1-chloro-2,4-dinitrobenzene (CDNB) was 22% lower in lung extracts from
      naphthalene-tolerant animals than in controls. These results indicate that
      induction of hepatic GSTs is substantial and may be an important factor in the
      development of tolerance to naphthalene.

PMID- 10959796
TI  - Phenol sulphotransferase SULT1A1 polymorphism in prostate cancer: lack of
      association.
AB  - Preliminary evidence suggests that genetic polymorphisms in certain enzymes
      involved in xenobiotic metabolism and chemical defense could modify a
      susceptibility to prostate cancer. In the present study, two recently described
      phenol sulphotransferase SULT1A1 alleles (SULT1A1*1, SULT1A1*2) were investigated
      using a polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) approach. Genotyping was performed on DNA isolated from white blood cells
      from 134 patients with prostate cancer and 184 healthy control subjects. Both the
      prostate cancer patients and the controls demonstrated similar frequencies of the
      variant allele SULT1A1*2 (35.1% vs 39.1%). Homozygosity for the variant allele
      was slightly less frequent in cancer patients than controls (12.7% vs 17.4%). Our
      study does not support the hypothesis that the phenol sulphotransferase variant
      allele SULT1A1*2 with a G/A transition at nucleotide 638 is a risk modifier for
      prostate cancer in the Caucasian population.

PMID- 10959797
TI  - Fluoride induces apoptosis by caspase-3 activation in human leukemia HL-60 cells.
AB  - Even though fluoride toxicity is increasingly being considered to be important,
      very little information is available on the mechanism of action of fluoride. In
      the present study, the toxicity of fluoride on human leukemia (HL-60) cells was
      investigated and the involvement of caspase-3 was also studied. Fluoride induced
      apoptosis in HL-60 cells in a dose- and time-dependent manner. Annexin staining
      and DNA ladder formation on agarose gel electrophoresis further revealed that HL
      60 cells underwent apoptosis on exposure to 2-5 mM fluoride. Western blotting
      using polyclonal anti-caspase-3 antibody and mouse anti-human poly(ADP-ribose)
      polymerase (PARP) monoclonal antibody was performed to investigate caspase-3 and
      PARP activity. Fluoride led to the activation of caspase-3 which was evident by
      the loss of the 32 kDa precursor and appearance of the 17 kDa subunit.
      Furthermore, intact 116 kDa PARP was cleaved by fluoride treatment as shown by
      the appearance of a cleaved 89 kDa fragment. The results clearly suggest that
      fluoride causes cell death in HL-60 cells by causing the activation of caspase-3
      which in turn cleaves PARP leading to DNA damage and ultimately cell death.

PMID- 10959798
TI  - Influence of Adriamycin and paraquat on antioxidant enzyme expression in primary
      rat hepatocytes.
AB  - The cytostatic Adriamycin and the herbicide paraquat form reactive oxygen species
      during enzymatic activation. Adriamycin, but not paraquat, is also able to
      intercalate into DNA and to interfere with DNA synthesis and transcription. We
      investigated the influence of both substances on antioxidant enzyme expression in
      primary rat hepatocytes. Treatment of hepatocytes with Adriamycin led to an
      increase in catalase and a decrease in MnSOD mRNA expression. In contrast,
      exposure of hepatocytes to paraquat resulted in an increase in both catalase and
      MnSOD message levels. CuZnSOD mRNA was not responsive to either treatment.
      Adriamycin almost completely inhibited RNA synthesis, but paraquat did not change
      either RNA or protein synthesis. Both substances induced lipid peroxidation as
      measured by the accumulation of malondialdehyde in the medium. These findings
      indicate that catalase and MnSOD are not regulated coordinately in hepatocytes
      and that ROS-producing agents can differentially influence expression of
      antioxidant enzymes depending on their capacity to inhibit transcription.

PMID- 10959799
TI  - Fumonisin hepatotoxicity is reduced in mice carrying the human tumour necrosis
      factor alpha transgene.
AB  - Our previous studies have indicated that tumour necrosis factor alpha (TNFalpha)
      is involved in fumonisin B1 (FB1)-induced toxic responses. To investigate the
      role of TNFalpha in FB1 toxicity further we employed male transgenic mice
      expressing human TNFalpha gene (TG) and their wild-type equivalent C57BL/6 (WT).
      It was hypothesized that TG animals would have enhanced response to FB1. Repeated
      subcutaneous treatment of animals with 2.25 mg/kg per day of FB1 for 5 days
      caused minimal changes in body weight, organ weights, blood cell counts, and
      TNFalpha levels in plasma 1 day after the last injection. The mRNA for TNFalpha
      in liver increased in both TG and WT after FB1 treatment, providing evidence that
      FB1 induces hepatic TNFalpha expression. Liver and kidney lesions were found in
      TG after FB1 treatment; however, liver lesions seen in FB1-treated TG were
      considerably less than those observed in WT. The decreased hepatotoxicity in TG
      after FB1 treatment correlated with plasma concentrations of alanine
      aminotransferase and aspartate aminotransferase. Free sphinganine levels
      increased significantly in both the liver and kidney of WT and TG mice treated
      with FB1. The increase of free sphinganine in the liver from TG mice was 40% less
      than in WT mice and paralleled the changes in serum liver enzymes. Regional brain
      neurotransmitters and their metabolites were increased to a similar extent by FB1
      in both WT and TG mice. Since the data did not support the original hypothesis,
      we investigated the levels of NFkappaB in liver. The cytosolic NFkappaB was
      significantly higher in TG compared with WT. Induction of NFkappaB, caused by
      increased endogenous production of TNFalpha, is a possible explanation of
      decreased FB1 hepatotoxicity in TG. The results suggest a protective role for
      NFkappaB in FB1-induced liver damage.

PMID- 10959800
TI  - Comparison of the effects of tamoxifen and toremifene on rat
      hepatocarcinogenesis.
AB  - The hepatoproliferative and cytochrome P450 enzyme inducing effects of two
      antiestrogens, tamoxifen and toremifene, were compared in female Sprague-Dawley
      rats using immunohistochemical staining methods. Equimolar doses of the
      antiestrogens (tamoxifen 45 mg/kg and toremifene 48 mg/kg) were given by oral
      administration to 6-week-old rats for 12 months including a 3-month recovery
      period. Controls received the vehicle carboxymethylcellulose. Altogether 90 rats
      were used in the study. Five rats per dose group were killed after 14 days, 5
      weeks, 3, 6 and 12 months of treatment as well as after the 3-month recovery
      period. Hepatocellular carcinoma was found in four out of five rats after 12
      months of tamoxifen treatment. After the 3-month recovery period all tamoxifen
      treated rats had large liver tumors (diameter up to 3 cm). No tumors were
      observed in toremifene-treated rats. Liver cell proliferation was measured by the
      index of proliferating cell nuclear antigen (PCNA) expression.
      Immunohistochemical staining with the placental form of glutathione S-transferase
      (GST-P) was used as a marker for preneoplastic foci. Cytochrome P450 induction
      was measured using specific antibodies to isoenzymes. Tamoxifen increased the
      incidence of GST-P-positive foci significantly by 3 months of treatment but
      toremifene did not as compared with the controls. Liver cell proliferation
      increased significantly only in the liver tumors of tamoxifen-treated rats after
      12 months of treatment and during the recovery period. Both antiestrogens induced
      the isoenzymes CYP2B1/2 and CYP3A1 within 14 days although tamoxifen was a more
      powerful inducer. Immunohistochemistry of rat liver sections showed a
      centrilobular localization of these induced enzyme proteins. The expression of
      CYP2B1/2 and 3A1 could also be observed in foci after 3 and 6 months of
      administration and in liver adenomas and in some carcinomas after 12 months of
      administration with tamoxifen. The results show that tamoxifen, but not
      toremifene, has the potential to induce and promote the development of rat
      hepatocarcinogenesis in this experimental model.

PMID- 10959801
TI  - Acute inhalation toxicity of polymeric diphenyl-methane 4,4'-diisocyanate in
      rats: time course of changes in bronchoalveolar lavage.
AB  - The early acute pulmonary response of Wistar rats exposed nose-only to respirable
      polymeric diphenylmethane 4,4'-diisocyanate (MDI) aerosol was examined. This
      study investigated the time course of the relationship between acute pulmonary
      irritation and ensuing disturbances of the air/blood barrier in rats exposed to
      concentrations of 0.7, 2.4, 8, or 20 mg MDI/m3. The duration of exposure was 6 h.
      The time-response relationship of MDI-induced acute lung injury was examined 0 h
      (directly after cessation of exposure), 3 h, 1 day, 3 days, and 7 days after
      exposure. Bronchoalveolar lavage (BAL) fluid was analyzed for markers indicative
      of injury of the bronchoalveolar region, i.e., angiotensin-converting enzyme,
      protein, alkaline phosphatase, lactate dehydrogenase, gamma
      glutamyltranspeptidase, and sialic acid. Phosphatidylcholine and acid phosphatase
      were determined in BAL fluid and cells. Glutathione was determined in BAL fluid
      and lung tissue. This analysis revealed no latent period of effects except a
      transiently delayed influx of cells and increased lung weights on postexposure
      days 1 and 3. Markedly loaded BAL cells with phosphatidylcholine were observed on
      day 1 only. In most instances, changes returned to the level of the air exposed
      control on day 7, except increased glutathione in lung tissue. The findings
      suggest that the most sensitive markers of dysfunction of the air/blood barrier
      are angiotensin-converting enzyme and protein, including alkaline phosphatase.
      The statistically significant increase in intracellular phosphatidylcholine and
      decreased intracellular acid phosphatase on the exposure day suggest that
      increased amounts of phospholipids are phagocytized by alveolar macrophages,
      associated with protracted lysosomal catabolism. Partially glutathione-depleted
      rats exposed to 20 mg/m3 experienced a more pronounced increase in BAL protein
      than normal rats. In summary, this study suggests that respirable polymeric MDI
      aerosol interacts directly with the air/blood barrier causing increased
      extravasation of plasma constituents as a result of increased permeability of
      capillary endothelial cells. Overall, a transient dysfunction of the pulmonary
      epithelial barrier occurred at level as low as 0.7 mg/m3 and appears to be
      related a dysfunction of pulmonary surfactant. Nonprotein sulfhydryl constituents
      appear to play a role as portal-of-entry specific modifying factors.

PMID- 10959802
TI  - Possible estrogenic and/or antiandrogenic effects of methoxychlor on prolactin
      release in male rats.
AB  - Methoxychlor (MTX) is a pesticide currently used as a substitute for dichloro
      diphenyl-trichloroethane (DDT). This organochloride insecticide has some
      estrogenic properties, and may modify the feedback mechanisms of steroids on the
      hypothalamus and pituitary. This work was undertaken to explore the possible
      effects of MTX on the episodic prolactin release and to analyze whether these
      effects are mediated by dopamine (DA), luteinizing hormone (LH), and/or
      testosterone. Adult male Sprague-Dawley rats were administered 25 mg/kg/day of
      MTX in sesame oil for 30 days. Control animals received vehicle only. The
      episodic prolactin release and plasma testosterone levels were measured as well
      as the dopamine (DA) content in the median eminence (ME) and in the anterior
      (AH), mediobasal (MBH), and posterior (PH) hypothalamus. The mean serum prolactin
      levels and absolute pulse amplitude of the hormone increased after the xenobiotic
      administration, whereas its relative pulse amplitude diminished. The frequency
      and duration of prolactin peaks and its half-life were not modified by the
      treatment with the pesticide. On the other hand, methoxychlor decreased the DA
      content in ME, increased it in AH, and did not change it in MBH or PH. MTX
      decreased plasma levels of LH and testosterone compared with controls. These data
      suggest estrogenic and antiandrogenic effects of MTX on the episodic prolactin
      secretion; the changes observed in prolactin release could be explained, at least
      in part, by some of the changes of DA at the hypothalamus and of LH at the
      pituitary, but not by changes of testosterone at the testicular level.

PMID- 10959803
TI  - Increased immunoreactivity of glutathione-S-transferase in the retina of Swiss
      Webster mice following inhalation of JP8 + 100 aerosol.
AB  - The current study was designed to determine whether exposure of mice to
      aerosolized jet fuel (JP8 + 100) resulted in changes in the cellular distribution
      or immunoreactivity of the enzyme glutathione S-transferase (GST), a biomarker of
      toxicant exposure. Male mice were exposed to JP8 + 100 at 1000 mg/m3 or 2500
      mg/m3 in aerosol for 1 h per day for 7 days and then sacrificed. The retinas were
      studied by immunohistochemical methods. The JP8 + 100 exposure caused a marked
      increase in the immunoreactivity of anti-GSTM antibodies with the radial glial
      cells of the retina, the Muller cells. These results are consistent with the
      hypothesis that JP8 + 100 acts as a toxicant to mouse retina by permitting the
      flux of materials across the blood-retina barrier. The findings are relevant to
      humans because recent studies indicate that Air Force personnel assigned to clean
      and maintain fuel pods may be exposed to concentrations of JP8 + 100 exceeding
      1000 mg/m3.

PMID- 10959804
TI  - 2-Phenoxyethanol: a neurotoxicant?

PMID- 10959805
TI  - A prospective study of interferon therapy modified by pre-treatment viral load in
      cirrhotic patients. Tokyo-Chiba Hepatitis Research Group.
AB  - BACKGROUND/AIMS: The relative role of hepatitis C virus (HCV) load and subtype as
      predictors of the efficacy of interferon therapy has been clarified in patients
      with chronic hepatitis C, but the effectiveness of interferon therapy in
      cirrhotic patients is still unclear. METHODS: To resolve this issue, we undertook
      a multicenter, randomized, and prospective study of 114 cirrhotic patients with
      hepatitis C virus infection. The patients were selected to undergo two different
      periods (6 or 12 months) of IFN therapy according to viral load. Patients with
      "low" viral load (< or = 10(5.8) copies/ml serum) were randomly divided into
      three groups, receiving 6 or 9 million units (MU) interferon three times a week
      for 6 months (total dose: 468 or 702 MU), or of a modified regimen using 6MU of
      IFN over 6 months (total dose 564 MU), while patients with "high" viral load (<
      or = 10(6.3) copies/ml serum) were also randomly divided into two groups of 6 or
      9 MU of IFN three times a week for 12 months (total dose: 936 or 1,404 MU).
      RESULTS: HCV-RNA negativity rate at the completion of treatment with 6 or 9 MU
      IFN was 65% in patients with "low" viral load, in contrast to 14% in patients
      with "high" viral load. Sustained virological response was found in 40% of
      patients with "low" viral load irrespective of the three different regimens, in
      contrast to only 1 out of 35 patients (3%) with "high" viral load. Viral
      eradication was found in approximately 50% of patients having a low virus load (<
      or = 10(4.3) copies/ml) and with HCV subtype 2a. Univariate and multivariate
      analysis revealed that pretreatment viral load was a significant factor
      contributing to efficacy of IFN therapy. CONCLUSIONS: Sustained response was
      scarcely achieved in cirrhotic patients with high viral loads even after a 12
      month course of intensive IFN therapy. This result indicates that there is a
      certain cut-off level of HCV RNA load which can not be eradicated.

PMID- 10959806
TI  - Clinical, virological and histopathological features: long-term follow-up in
      patients with chronic hepatitis C co-infected with S. mansoni.
AB  - BACKGROUND/AIMS: Infection with Schistosoma mansoni is endemic in Egypt leading
      to hepatic schistosomiasis and eventually portal hypertension. The prevalence of
      antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the
      present study was to investigate the influence of schistosomiasis on chronic
      hepatitis C with respect to the natural course of the disease, immunology,
      virology and histology. PATIENTS AND METHODS: One hundred and twenty-six Egyptian
      patients classified into three groups: group A: chronic hepatitis C (n=33); group
      B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic
      schistosomiasis (n=63) were enrolled and prospectively followed for 62.7 +/- 22
      months. Patients infected with other hepatic viruses and/or parasites were
      excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts
      in blood, hematological and blood chemical values, abdominal ultrasonography,
      upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity
      index in the liver biopsy were determined. RESULTS: Thirty patients (48%) with
      HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%)
      in HCV patients and none in the schistosomal group. HCV RNA levels ranged between
      0.07 and 13 x 10(5) copies/ml in group A, and between 1 and 25 x 10(5) copies/ml
      in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%)
      and 21 patients with HCV alone (64%). Patients with coinfection showed higher
      grading and staging scores in their liver biopsies. Hepatocellular carcinoma was
      detected only in patients with coinfection. During follow-up, the mortality rate
      was 12%, 3% and 48% in group A, B and C, respectively. CONCLUSIONS: Patients with
      concomitant HCV and schistosomiasis infection were characterized by more advanced
      liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher
      histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma
      as well as a much higher mortality rate.

PMID- 10959807
TI  - Long-term responders without eradication of hepatitis C virus after interferon
      therapy: characterization of clinical profiles and incidence of hepatocellular
      carcinoma.
AB  - AIMS/BACKGROUND: The aim of this study was to determine the characteristics of
      patients with chronic hepatitis C showing long-term normalization of alanine
      aminotransferase (ALT) without eradication of HCV RNA, as well as to investigate
      the incidence of hepatocellular carcinoma (HCC) in such patients. METHODS: Four
      hundred and nineteen patients with histologically-proven chronic hepatitis C who
      had received interferon (IFN) therapy were studied. Complete response (CR) was
      defined as persistent normalization of ALT levels with eradication of serum HCV
      RNA (n= 126). Long-term biochemical response with positive HCV RNA (HCV-positive
      BR) was defined as a normal ALT level at 6 months after IFN therapy with further
      persistent normalization of ALT levels for 2 or more years without eradication of
      serum HCV RNA (n=49). All other patterns were classified as non-response (NR,
      n=244). RESULTS: Mean follow-up periods of CR, HCV-positive BR and NR groups were
      4.9, 5.2 and 4.9 years, respectively. The HCV-positive BR group had significantly
      higher serum HCV RNA levels and a higher rate of HCV serological group 1
      classification than the CR group. The other characteristics of the HCV-positive
      BR group were lower histologic activity, lower ALT levels, and a higher rate of
      females when compared with both the CR and NR groups. Histologic staging in the
      HCV-positive BR group was significantly lower than that in the NR group.
      Cumulative incidences of HCC estimated by the Kaplan-Meier method in both the CR
      and HCV-positive BR groups were significantly lower than those in the NR group
      (log-rank test, CR vs NR p<0.001, HCV-positive BR vs NR p=0.026). CONCLUSION: The
      patients with HCV-positive BR were virologically different from those with CR,
      and had lower ALT levels and histologic activity when compared to those with CR
      and NR.

PMID- 10959809
TI  - Role of serum soluble Fas/soluble Fas ligand and TNF-alpha on response to
      interferon-alpha therapy in chronic hepatitis C.
AB  - AIMS/BACKGROUND: To determine the relationship between host factors and host
      response to interferon (IFN) therapy, serum soluble Fas (sFas), soluble Fas
      ligand (sFas ligand), and tumor necrosis factor-alpha (TNF-alpha) were analyzed
      in 41 patients with chronic hepatitis C (CH-C) treated with IFN-alpha. METHODS:
      Serum levels of sFas, sFas ligand, and TNF-alpha were measured at 0, 4, and 24
      weeks of IFN therapy. RESULTS: Eighteen patients were complete responders (CR)
      and 23 patients were non-responders (NR). Serum levels of sFas and TNF-alpha in
      patients with CHC were significantly higher than those in healthy controls
      (p<0.01 and p<0.01, respectively). Serum sFas ligand levels were significantly
      lower in CH-C patients than in healthy controls (p<0.01). Before IFN therapy,
      serum levels of sFas in NR were significantly higher than those in CR (p<0.05).
      At 4 weeks of IFN therapy, serum levels of sFas of CR were significantly elevated
      compared with levels before IFN therapy (p<0.05). Serum levels of sFas correlated
      with the histological activity of the liver (p<0.05) and alanine aminotransferase
      (p<0.05). None of the three parameters, serum sFas, sFas ligand, or TNF-alpha
      levels, correlated with each other, with HCV-RNA genotype or with serum HCV-RNA
      load. Multiple logistic regression analysis showed that serum sFas levels before
      IFN therapy were a contributive factor to predict efficacy of IFN therapy.
      CONCLUSIONS: Serum sFas/sFas ligand and TNF-alpha play a possible role in
      pathogenesis of CH-C and also in IFN therapy. Serum sFas levels before IFN
      therapy may be one of the host-related factors used for evaluating the response
      of CH-C patients to IFN therapy.

PMID- 10959808
TI  - Connective tissue growth factor in human liver cirrhosis.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) belongs to a family of factors
      that regulate fibrogenesis and wound healing. While the significance of
      transforming growth factor beta (TGF-beta) in liver fibrosis is well established,
      the role of CTGF in fibrosing hepatopathy is still unknown. METHODS: CTGF was
      analyzed in 10 normal and in 16 cirrhotic liver tissue samples. Northern blot
      analysis was used to examine the concomitant expression of CTGF and TGF-beta1
      mRNAs, and the cellular localization of CTGF mRNA was studied by in situ
      hybridization. For identification of myofibroblasts and activated hepatic
      stellate cells, alpha-smooth muscle actin (alpha-SMA) immunohistochemistry was
      used. RESULTS: Northern blot analysis showed 6.5-fold enhanced expression of CTGF
      mRNA and 7.8-fold enhanced expression of TGF-beta1 mRNA in liver cirrhosis in
      comparison with normal controls (p<0.01). By in situ hybridization, CTGF mRNA was
      detectable in only a few spindle cells in the portal tracts in normal liver
      samples. In contrast, there was strong expression of CTGF mRNA in fibroblasts and
      myofibroblast-like cells present in fibrous septa surrounding the cirrhotic
      nodules, in stellate cells, in endothelial cells and in mesenchymal cells around
      ductular proliferations, and in ductular epithelial cells. There was a strong
      correlation between CTGF mRNA and TGF-beta1 mRNA as well as the degree of
      fibrosis (p<0.01). CONCLUSIONS: Overexpression of CTGF in liver cirrhosis,
      especially in fibroblasts/myofibroblasts and stellate cells, suggests that this
      novel factor may play an important role in hepatic fibrosis.

PMID- 10959810
TI  - Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a
      low-endemic area.
AB  - AIMS/BACKGROUND: This study was undertaken in order to assess the main features
      of hepatocellular carcinoma in Germany, a country with low incidences of this
      tumor. METHODS: Two hundred and eighty consecutive patients with hepatocellular
      carcinomas admitted to the Medical School Hannover between 1993-1997 were
      retrospectively studied. RESULTS: Reliable data for the assessment of the
      etiology and the tumor stage of HCC were available for 268 patients. The
      female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with
      hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9%) with HCV and
      10% coinfection with HBV/HCV This result emphasizes the major impact of HBV and
      HCV infection in liver cancer in Germany. Of all patients with HCC 74.6%) had
      liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the
      liver: in only 5.9% could regional lymph node metastases as well as 8.5%)
      metastases in other organs be clinically diagnosed by chest X-ray, computed
      tomography scan or sonography. Data to asses the Okuda tumor stage were available
      for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as
      stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the
      AFP value was elevated, but only in 30% did the AFP level reach the value of 500
      microg/l, which is considered to be significant for HCC diagnosis in patients
      with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%)
      versus HBV (80.6%) associated HCC, which was the only significant (p<0.05)
      difference in the characteristics of HCC according to the etiology. CONCLUSION:
      Our study shows that liver cirrhosis is the prime risk factor for
      hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis
      virus related HCC, in particular the high proportion of HBV infections,
      contradicts the common view that alcohol is by far the most important etiological
      factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as
      Germany.

PMID- 10959811
TI  - Inhibition of lipopolysaccharide-induced I-kappaB degradation and tumor necrosis
      factor-alpha expression by dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene
      dioxybiphenyl-2,2'-dicarboxylate (DDB): minor role in hepatic detoxifying enzyme
      expression.
AB  - AIMS/BACKGROUND: Dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'
      dicarboxylate (DDB) is active against a variety of hepatotoxins and has been used
      as a curative agent for patients with acute and chronic viral hepatitis. Effects
      of DDB on the expression of xenobiotic-metabolizing enzymes and on nuclear factor
      kappaB (NF-kappaB) activation and tumor necrosis factor-alpha (TNF-alpha)
      production by lipopolysaccharide (LPS), an endotoxin involved in inflammatory
      responses, were examined in rats and in RAW264.7 cells to investigate mechanistic
      aspects. METHODS: Expression of hepatic cytochrome P450s, microsomal epoxide
      hydrolase and glutathione S-transferases was determined by immunoblot and
      Northern blot analyses. Activation of hepatic NF-kappaB and I-kappaBalpha
      degradation was assessed by gel mobility shift and immunoblot analyses,
      respectively. LPS-induced TNF-alpha expression was monitored in rats and in
      RAW264.7 cells by enzyme-linked immunosorbent assay and/or reverse transcription
      polymerase chain reaction analysis. RESULTS: DDB failed to alter the expression
      of hepatic cytochrome P450 1A and 2C11, microsomal epoxide hydrolase and
      glutathione S-transferases in rats with slight inhibition of P450 2E1 expression,
      but induced P450 2B1/2. Pretreatment of rats with DDB prevented LPS-induced
      hepatic I-kappaBalpha degradation and the resultant NF-kappaB activation, and
      inhibited the LPS-induced plasma TNF-alpha protein and hepatic TNF-alpha mRNA
      expression in a dose-dependent manner. LPS-induced I-kappaBalpha degradation and
      TNF-alpha production were also inhibited by DDB in RAW264.7 cells, which was
      consistent with the results in rats. CONCLUSIONS: The present study demonstrated
      that DDB may inhibit inflammatory responses in association with reduction of NF
      kappaB activation through prevention of I-kappaBalpha degradation and subsequent
      TNF-alpha production, but not with modulation of the detoxifying enzyme
      expression.

PMID- 10959812
TI  - Plasma elimination of cholyl-lysyl-fluorescein (CLF): a pilot study in patients
      with liver cirrhosis.
AB  - BACKGROUND: Cholyl-lysyl-fluorescein (CLF) is a fluorescein-labelled bile acid
      whose biological behaviour closely resembles that of naturally occurring cholyl
      glycine. AIM: The aim of this study was to analyze the CLF plasma elimination in
      patients with liver cirrhosis. METHODS: A dose of CLF at 0.02 mg/kg b.w. was
      administered i.v. in 26 patients with liver cirrhosis and 9 healthy volunteers.
      Blood samples were collected before injection and then at 10 min intervals over
      60 min. Plasma fluorescence was measured by a luminescence spectrometer and
      residual fluorescence over the time of the study was compared in each group.
      Routine liver function tests (rLFTs) were performed before each injection.
      RESULTS: Plasma elimination of CLF was significantly impaired in patients with
      cirrhosis compared to healthy subjects with p values <0.0001 at each analyzed
      time point. CLF test showed 100% sensitivity for liver cirrhosis when residual
      fluorescence was measured 30, 40, 50 and 60 min after injection. Routine LFTs
      showed 85% sensitivity for bilirubin, 84% for total bile acids, 69% for aspartate
      aminotransferase 62% for albumin and 50% for alkaline phosphatase. CLF
      elimination measured 60 min after injection correlated with Child-Pugh score
      (r=0.3945; p<0.05) and albumin (rs=0.6451; p<0.001). No adverse reaction or side
      effects of CLF were observed. CONCLUSIONS: CLF test clearly distinguished between
      the two analyzed groups and was more sensitive than routine liver function tests.
      The test appears safe, simple to perform and analyze and after validation in
      larger cohorts of patients may have the potential to become a useful dynamic test
      of liver function.

PMID- 10959813
TI  - Improved response to ribavirin interferon combination compared with interferon
      alone in patients with type 4 chronic hepatitis C without cirrhosis.
AB  - Response to treatment with alpha interferon with or without concomitant ribavirin
      varies according to the viral genotype in patients with chronic hepatitis C. AIM:
      This study was undertaken in order to determine the response of genotype 4
      chronic hepatitis C to interferon and ribavirin combination compared to
      interferon alone in patients without cirrhosis. METHODS: Fifty-two patients were
      given interferon alone at a dose of 5 million units, 3 times a week and another
      60 patients were administered with interferon combined with ribavarin (1,000
      1,200 mg/ day) for 24 weeks. Sustained biochemical response was defined as normal
      ALT, 6 months after end of therapy. Sustained virologic response was defined as
      negative HCV RNA, 6 months after the end of therapy. RESULTS: Only 10/52 (19%)
      patients showed sustained biochemical response after interferon alone, while
      31/60 (52%) showed sustained biochemical response after interferon combined with
      ribavirin (p<0.01). Only 4/52 (8%) patients showed sustained virologic response
      after interferon alone, while 25/60 (42%) showed sustained virologic response
      after interferon combined with ribavirin (p<0.001). CONCLUSION: These results
      show that patients with chronic hepatitis due to hepatitis C virus type 4 show a
      poor response to interferon alone but a better response to interferon combined
      with ribavirin.

PMID- 10959814
TI  - Sequential occurrence of primary sclerosing cholangitis and autoimmune hepatitis
      type III in a patient with ulcerative colitis: a follow up study over 14 years.
AB  - In 1983, a female patient born in 1963 presented with symptoms of ulcerative
      colitis and typical clinical and histological signs of primary sclerosing
      cholangitis (PSC). At this time only pANCA were positive while other marker
      antibodies for autoimmune liver disorders could not be detected. In summer 1987
      the clinical picture changed and was replaced by laboratory and histological
      signs typical of autoimmune hepatitis (AIH). Thus, IgG levels increased
      considerably and cholestatic enzymes became normal. For the first time, anti
      liver-pancreas antibodies (LP), a diagnostic marker for AIH type III could be
      detected. In the following years several relapses occurred also induced by
      repeated discontinuation of immunosuppressive therapy. Symptoms of colitis
      persisted but signs of cholestasis remained absent for the following ten years.
      In 1997, colitis exacerbated again and colectomy had to be performed together
      with liver transplantation. Surprisingly, histology of the explanted liver now
      showed the typical features of PSC stage III/IV while the significant criteria
      for AIH were now lacking. Thus, progression to cirrhosis was, probably, mainly
      induced by the biliary destructive and fibrotic process although biochemical and
      serological data were clearly indicative of an autoimmune, i.e. AIH-related
      manifestation.

PMID- 10959815
TI  - Mitochondrial diseases represent a risk factor for valproate-induced fulminant
      liver failure.
AB  - We report on 3 siblings (2 females and 1 male) with chronic progressive external
      ophthalmoplegia (CPEO), compatible with inherited mitochondrial cytopathy. The
      younger of the two sisters died at the age of 37 due to progressive respiratory
      failure. The older one presented with a status epilepticus at the age of 39 and
      was treated with valproate. Five months after the start of treatment, she
      developed fulminant liver failure and died. The brother has suffered from CPEO
      since early childhood but has had so far no other symptoms of a mitochondrial
      disease. A muscle biopsy from the younger sister revealed ragged-red fibers and
      decreased activities of complex I and IV of the respiratory chain but no
      pathogenic mutations in the mitochondrial tRNA genes or in several locations in
      the coding region of the mitochondrial genome. In the older sister's liver
      (obtained post-mortem), mitochondrial DNA was fragmented and could not be
      investigated. The clinical presentation and the biochemical findings suggest that
      all 3 siblings suffered from a mitochondrial cytopathy. Since mitochondrial
      cytopathies and valproate-induced fulminant liver failure are both rare events,
      an association between them is likely. Mitochondrial diseases should therefore be
      considered as a risk factor for valproate-induced liver failure and be excluded
      before treatment with valproate.

PMID- 10959816
TI  - The molecular basis of glucocorticoid-induced apoptosis of lymphoblastic leukemia
      cells.
AB  - Glucocorticoids (GCs) induce programmed cell death with the morphologic
      characteristics of apoptosis in cells of the lymphoid lineage at certain stages
      of differentiation. Although the physiological significance of this phenomenon is
      not well understood, it has been exploited to a great extent in the therapy of
      malignant lymphoproliferative disorders. In spite of its clinical importance, the
      molecular mechanisms underlying GC-induced apoptosis and -clinically even more
      important resistance to this phenomenon are not known. This review summarizes
      efforts from our and other laboratories addressing these issues in human
      lymphoblastic leukemia, with particular emphasis on the CCRF-CEM childhood T-cell
      leukemia model. These studies have shed some light on the downstream execution
      phase of GC-induced apoptosis but the critical upstream gene regulatory events
      have remained a mystery. Very recent DNA chip-based expression profile analyses
      in our laboratory along with data from the literature have, however, suggested
      that GC receptor auto-upregulation in sensitive target cells might be the
      critical event leading to persistent downregulation of central metabolic pathways
      which is incompatible with cell survival. The validity of this hypothesis and its
      possible clinical implications are currently being investigated in our
      laboratory.

PMID- 10959817
TI  - Immunolocalization of calcineurin and FKBP12, the FK506-binding protein, in
      Hassall's corpuscles of human thymus and epidermis.
AB  - Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, plays an important
      role in various physiological functions including T cell activation. This enzyme
      is a target molecule for the immunosuppressants, cyclosporin A and FK506. In the
      present study, we investigated immunohistochemical localization of calcineurin
      and FKBP12, an FK506-binding protein, in human thymus and epidermis. The
      catalytic subunit (calcineurin A) of calcineurin was abundantly expressed in
      Hassall's corpuscles which were localized in the thymic medulla and represented
      the terminal stages of thymic medullary epithelium. The regulatory subunit
      (calcineurin B) of calcineurin was also expressed in high amounts in Hassall's
      corpuscles. In the epidermis, which shows similarities to Hassall's corpuscles,
      both subunits were also abundantly expressed, and their expression increased with
      the differentiation of keratinocytes. FKBP12 was observed to be expressed
      abundantly, both in Hassall's corpuscles and the entire epidermis. These findings
      suggest that the differentiated forms of the two cell types, which are the thymic
      medullary epithelial cell and the keratinocyte, are the target for
      pharmacological actions of FK506.

PMID- 10959818
TI  - Localization of porcine trappin-2 (SKALP/elafin) in trachea and large intestine
      by in situ hybridization and immunohistochemistry.
AB  - Trappin-2 (SKALP/elafin), an elastase inhibitor, belongs to a unique family of
      proteinase inhibitors that are covalently anchored at the site of action through
      their transglutaminase substrate domain and are collectively called trappins. The
      transglutaminase substrate domain is therefore called "cementoin moiety".
      Currently, human, porcine, and bovine trappin-2 (SKALP/elafin) have been
      characterized. Previously, we showed that porcine trappin-2 (SKALP/elafin) occurs
      mainly in the trachea and large intestine. To determine the localization of
      trappin-2 (SKALP/elafin) at the cellular level, we carried out in situ
      hybridization and immunohistochemistry using the porcine trachea and large
      intestine and found that trappin-2 (SKALP/elafin) is produced in the goblet cells
      of the tracheal epithelium and of the large intestinal crypts. These locations
      suggest that trappin-2 (SKALP/elafin) is secreted onto the luminal surface of the
      trachea and crypts of Lieberkuhn and plays a protective role against destructive
      bacterial proteinases.

PMID- 10959819
TI  - Immunohistochemical detection of cathepsin D, K, and L in the process of
      endochondral ossification in the human.
AB  - Cathepsins D, K, and L were immunolocalized in tissue undergoing endochondral
      ossification in the human. Cathepsins D, K, and L were localized in osteoclasts
      and chondroclasts attached to bone matrix and cartilage matrix, respectively.
      Cathepsins D and L were immunostained in chondrocytes. Immunolocalization of
      cathepsin D was limited to hypertrophic chondrocytes adjacent to the
      osteochondral junction. In contrast, cathepsin L was immunolocalized in both
      proliferating and hypertrophic chondrocytes. In the bone marrow space, cathepsins
      D, K, and L were localized in multinucleated cells. Cathepsin D was diffusely
      detected in mononuclear bone marrow cells which were negative for cathepsins K
      and L. The present findings indicated that cathepsins K, D, and L were associated
      with the process of endochondral ossification in the human, and suggested that
      these cathepsins share roles in bone and cartilage turnover in the human.

PMID- 10959820
TI  - NADPH oxidase subunits and superoxide production in porcine pulmonary artery
      endothelial cells.
AB  - An NADPH oxidase complex composed of a membrane-bound flavocytochrome b558
      consisting of two subunits (p22phox and gp91phox) and cytosolic activating
      factors (p47phox and p67phox) generates superoxide anions from oxygen in the
      respiratory burst of phagocytic cells. Inconsistent results have been previously
      obtained concerning its additional occurrence in pulmonary artery endothelial
      cells (PAEC), and this issue was addressed in the present study. PAEC isolated
      from porcine pulmonary trunk contained mRNA for p22phox and gp91phox as
      demonstrated by reverse transcription-polymerase chain reaction.
      Immunohistochemistry demonstrated cytochrome subunits, p22phox, gp91phox,
      p47phox, and p67phox, both in vitro in isolated PAEC and in situ in endothelial
      cells in tissue sections of the pulmonary trunk. Isolated PAEC generated reactive
      oxygen species (ROS; measured by lucigenin-induced chemiluminescence and
      conversion of dihydrorhodamine 123 into rhodamine 123) in response to stimulation
      with phorbol 12-myristate 13-acetate. This stimulated ROS production was
      sensitive to the flavoprotein inhibitor diphenylene-iodonium, and reduced when
      the superoxide scavenger superoxide dismutase was added. Chemiluminescence
      measurements of superoxide generation by stimulated PAEC accounted for
      approximately 1% of that generated by stimulated peritoneal macrophages. The data
      demonstrate a low-output NADPH oxidase system in porcine PAEC sharing several
      components with that identified in phagocytic cells.

PMID- 10959821
TI  - Differences in the distribution of synemin, paranemin, and plectin in skeletal
      muscles of wild-type and desmin knock-out mice.
AB  - Mice lacking the gene encoding for the intermediate filament protein desmin have
      a surprisingly normal myofibrillar organization in skeletal muscle fibers,
      although myopathy develops in highly used muscles. In the present study we
      examined how synemin, paranemin, and plectin, three key cytoskeletal proteins
      related to desmin, are organized in normal and desmin knock-out (K/O) mice. We
      show that in wild-type mice, synemin, paranemin, and plectin were colocalized
      with desmin in Z-disc-associated striations and at the sarcolemma. All three
      proteins were also present at the myotendinous junctions and in the postsynaptic
      area of motor endplates. In the desmin K/O mice the distribution of plectin was
      unaffected, whereas synemin and paranemin were partly affected. The Z-disc
      associated striations were in general no longer present in between the
      myofibrils. In contrast, at the myotendinous and neuromuscular junctions synemin
      and paranemin were still present. Our study shows that plectin differs from
      synemin and paranemin in its binding properties to the myofibrillar Z-discs and
      that the cytoskeleton in junctional areas is particularly complex in its
      organization.

PMID- 10959823
TI  - Simultaneous enzyme overlay membrane (EOM)-based in situ zymography and
      immunofluorescence technique reveals cathepsin B-like activity in a subset of
      tumour vessels.
AB  - The analysis of the invasion front of oral squamous cell carcinoma (OSCC) has
      revealed a fundamental invasion-associated remodelling of the extracellular
      matrix as the result of a complex regulated interplay of matrix synthesis and
      matrix degradation. Cysteine proteinases, in particular cathepsin B, are
      implicated in tumour invasion in vivo and in vitro and are thought to be
      important mediators of metastasis. An in situ zymographic assay based on enzyme
      overlay membranes (EOMs) was established to define the tissue localisation of
      cathepsin B activity in OSCC. Using confocal laser scanning microscopy we present
      a double-labelling method for the rapid and reproducible simultaneous detection
      of cathepsin B-like activity and cellular or extracellular antigens based on an
      EOM and immunofluorescence technique on frozen sections. Applying this method,
      cathepsin B-like activity was mainly found in vascular structures within the
      invasive front of OSCC. Therefore, the results suggest a particular pathogenic
      role of cathepsin B in tumour angioneogenesis. The method can simply be
      transferred to other enzymes and can be recommended for more extensive studies of
      proteolytic activity in human malignancies.

PMID- 10959822
TI  - Alveolar epithelial type II cell apoptosis in vivo during resolution of
      keratinocyte growth factor-induced hyperplasia in the rat.
AB  - Keratinocyte growth factor (KGF) induces rapid and transient hyperplasia of
      alveolar epithelial type II cells. We sought to determine components of the
      apoptotic process involved in the resolution of this hyperplasia and the fate of
      the apoptotic cells. Rats received intrabronchial instillation of 5 mg KGF/kg
      body weight or diluent. Lungs were fixed 1, 2, 3, 5, and 7 days later. Apoptosis
      was identified by TdT-mediated dUTP nick-end labeling (TUNEL), double-labeling
      for TUNEL and the type II cell marker MNF116, and electron microscopy. Fas, FasL,
      Bax, Bcl-2, and pro- and active caspase-3 were studied by immunohistochemistry.
      Changes were quantified by stereology. Cell type specificity was investigated by
      immunofluorescence double staining. Type II cells exhibited Fas, FasL, Bcl-2, and
      procaspase-3 irrespective of treatment and time. Immunoelectron microscopy
      revealed Fas at the apical type II cell membrane. Bax staining was prominent in
      controls (45-95% of type II cell surface fraction), markedly decreased during
      hyperplasia at days 2 (20-40%) and 3 (0-10%), and reappeared at day 7 (25-45%)
      when apoptosis was prominent. Remnants of apoptotic type II cells were
      incorporated in membrane-bound vacuoles of type II cell neighbors as well as
      alveolar macrophages. The results indicate that type II cells can enter the
      Fas/FasL/caspase-3 pathway regulated by Bax and Bcl-2. High Bcl-2:Bax levels
      favor type II cell survival and a low rate of apoptosis during hyperplasia. Low
      Bcl-2:Bax levels favor type II cell apoptosis during resolution. Because of time
      dependent changes that occur within a short time, the KGF-treated rat lung
      provides a useful in vivo model to investigate apoptosis in the context of tissue
      remodeling and repair.

PMID- 10959824
TI  - Cellular localization of the cystic fibrosis transmembrane conductance regulator
      in mouse intestinal tract.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP and cGMP
      regulated chloride channel critical to the regulation of intestinal fluid,
      chloride, and bicarbonate secretion. In cystic fibrosis (CF), mutations in CFTR
      result in downregulation of CFTR function and small intestinal obstruction.
      Unlike the human CF intestine, severe gastrointestinal disease and lethal
      obstruction is common in transgenic mice deficient in CFTR. The relevance of the
      physiology of CFTR and pathophysiology of CF in genetically altered mice to that
      of human CF disease remains incompletely understood. We hypothesized that the
      expression and distribution of CFTR in mouse intestine may differ from that of
      human and may contribute to the variation in disease expression between the two
      species. Using immunocytochemical and immunoblot techniques and well
      characterized anti-rodent anti-CFTR antibodies, we examined the cellular
      distribution of CFTR in the mouse intestinal tract. We identified significant
      differences in villus distribution for CFTR in the mouse proximal small intestine
      compared to those previously reported for human and rat. These observations are
      important to the understanding of CFTR pathophysiology in transgenic CF mouse
      model systems and bear relevance to the different phenotypic expression of
      disease in mice compared to human.

PMID- 10959825
TI  - Information theory in the brain.

PMID- 10959826
TI  - Cytokinesis: Sid signals septation.

PMID- 10959827
TI  - Perceiving emotion: There's more than meets the eye.

PMID- 10959828
TI  - Plant development: Keeping your distance.

PMID- 10959829
TI  - Virus structures: Those magnificent molecular machines.

PMID- 10959830
TI  - Wnt signaling: Moving in a new direction.

PMID- 10959832
TI  - Brain development: Lightning is always seen, thunder always heard.

PMID- 10959831
TI  - Neuronal patterning: Making stripes in the spinal cord.

PMID- 10959833
TI  - Suppressor T cells: Rebirth, function and homeostasis.

PMID- 10959834
TI  - Weighting to go with the flow?

PMID- 10959835
TI  - Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain
      development.
AB  - BACKGROUND: The extracellular protein Reln controls neuronal migrations in parts
      of the cortex, hippocampus and cerebellum. In vivo, absence of Reln correlates
      with up-regulation of the docking protein Dab1 and decreased Dab1 tyrosine
      phosphorylation. Loss of the Reln receptor proteins, apolipoprotein receptor 2
      and very low density lipoprotein receptor, results in a Reln-like phenotype
      accompanied by increased Dab1 protein expression. Complete loss of Dab1, however,
      recapitulates the Reln phenotype. RESULTS: To determine whether Dab1 tyrosine
      phosphorylation affects Dab1 protein expression and positioning of embryonic
      neurons, we have identified Dab1 tyrosine phosphorylation sites. We then
      generated mice in which the Dab1 protein had all the potential tyrosine
      phosphorylation sites mutated. This mutant protein is not tyrosine phosphorylated
      during brain development and is not upregulated to the extent observed in the
      Reln or the apoER2 and VLDLR receptor mutants. Animals expressing the non
      phosphorylated Dab1 protein have a phenotype similar to the dab1-null mutant.
      CONCLUSIONS: Dab1 is downregulated by the Reln signal in neurons in the absence
      of tyrosine phosphorylation. Dab1 tyrosine phosphorylation sites and not
      downregulation of Dab1 protein are required for Reln signaling.

PMID- 10959836
TI  - A critical role for histone H2AX in recruitment of repair factors to nuclear foci
      after DNA damage.
AB  - BACKGROUND: The response of eukaryotic cells to double-strand breaks in genomic
      DNA includes the sequestration of many factors into nuclear foci. Recently it has
      been reported that a member of the histone H2A family, H2AX, becomes extensively
      phosphorylated within 1-3 minutes of DNA damage and forms foci at break sites.
      RESULTS: In this work, we examine the role of H2AX phosphorylation in focus
      formation by several repair-related complexes, and investigate what factors may
      be involved in initiating this response. Using two different methods to create
      DNA double-strand breaks in human cells, we found that the repair factors Rad50
      and Rad51 each colocalized with phosphorylated H2AX (gamma-H2AX) foci after DNA
      damage. The product of the tumor suppressor gene BRCA1 also colocalized with
      gamma-H2AX and was recruited to these sites before Rad50 or Rad51. Exposure of
      cells to the fungal inhibitor wortmannin eliminated focus formation by all repair
      factors examined, suggesting a role for the phosphoinositide (PI)-3 family of
      protein kinases in mediating this response. Wortmannin treatment was effective
      only when it was added early enough to prevent gamma-H2AX formation, indicating
      that gamma-H2AX is necessary for the recruitment of other factors to the sites of
      DNA damage. DNA repair-deficient cells exhibit a substantially reduced ability to
      increase the phosphorylation of H2AX in response to ionizing radiation,
      consistent with a role for gamma-H2AX in DNA repair. CONCLUSIONS: The pattern of
      gamma-H2AX foci that is established within a few minutes of DNA damage accounts
      for the patterns of Rad50, Rad51, and Brca1 foci seen much later during recovery
      from damage. The evidence presented strongly supports a role for the gamma-H2AX
      and the PI-3 protein kinase family in focus formation at sites of double-strand
      breaks and suggests the possibility of a change in chromatin structure
      accompanying double-strand break repair.

PMID- 10959837
TI  - Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to
      control transcription required for M-phase.
AB  - BACKGROUND: The 'CLB2 cluster' in Saccharomyces cerevisiae consists of
      approximately 33 genes whose transcription peaks in late G2/early M phase of the
      cell cycle. Many of these genes are required for execution of the mitotic program
      and then for cytokinesis. The transcription factor SFF (SWI5 factor) is thought
      to regulate a program of mitotic transcription in conjunction with the general
      transcription factor Mcm1p. The identity of SFF has yet to be determined; hence
      further understanding of the mechanisms that regulate entry to M phase at the
      transcriptional level requires characterization of SFF at the molecular level.
      RESULTS: We have purified the biochemical activity corresponding to SFF and
      identified it as the forkhead transcription factor Fkh2p. Fkh2p assembles into
      ternary complexes with Mcm1p on both the SWI5 and CLB2 cell-cycle-regulated
      upstream activating sequence (UAS) elements in vitro, and in an Mcm1 p-dependent
      manner in vivo. Another closely related forkhead protein, Fkh1p, is also
      recruited to the CLB2 promoter in vivo. We show that both FKH1 and FKH2 play
      essential roles in the activation of the CLB2 cluster genes during G2-M and in
      establishing their transcriptional periodicity. Hence, Fkh1p and Fkhp2 show the
      properties expected of SFF, both in vitro and in vivo. CONCLUSIONS: Forkhead
      transcription factors have redundant roles in the control of CLB2 cluster genes
      during the G2-M period of the cell cycle, in collaboration with Mcm1p.

PMID- 10959838
TI  - Crystal structure of the worm NitFhit Rosetta Stone protein reveals a Nit
      tetramer binding two Fhit dimers.
AB  - BACKGROUND: The nucleotide-binding protein Fhit, among the earliest and most
      frequently inactivated proteins in lung cancer, suppresses tumor formation by
      inducing apoptosis. In invertebrates, Fhit is encoded as a fusion protein with
      Nit, a member of the nitrilase superfamily. In mice, the Nit1 and Fhit genes have
      nearly identical expression profiles. According to the Rosetta Stone hypothesis,
      if the separate Nit and Fhit genes could be shown to occur in the same subset of
      genomes (that is, to share a phylogenetic profile), then the existence of a
      fusion protein in invertebrates and the coordinated expression of separate mRNAs
      in mouse suggest that Nit and Fhit function in the same pathway and that the
      structure of invertebrate NitFhit may reflect the nature of Nit-Fhit
      interactions. RESULTS: To satisfy the phylogenetic profile criterion for
      functional significance of protein fusion events, we cloned additional Nit
      homologs from organisms with Fhit homologs. We used fluorescent nucleotide
      analogs of ApppA to follow the purification and to characterize the nucleotide
      specificity of NitFhit from Caenorhabditis elegans, crystallized the 200 kDa
      tetrameric complex, and solved the structure of NitFhit from a single mercury
      derivative phased by two-wavelength anomalous diffraction. CONCLUSIONS: Nit
      monomers possess a new alpha-beta-beta-alpha sandwich fold with a presumptive Cys
      Glu-Lys catalytic triad. Nit assembles into a tetrameric, 52-stranded beta box
      that binds Fhit dimers at opposite poles and displays Nit active sites around the
      middle of the complex. The most carboxy-terminal beta strand of each Nit monomer
      exits the core of the Nit tetramer and interacts with Fhit. Residence in the
      NitFhit complex does not alter the nucleotide specificity of Fhit dimers, which
      are oriented with ApppA-binding surfaces away from Nit.

PMID- 10959839
TI  - Interaction between PCNA and DNA ligase I is critical for joining of Okazaki
      fragments and long-patch base-excision repair.
AB  - DNA ligase I belongs to a family of proteins that bind to proliferating cell
      nuclear antigen (PCNA) via a conserved 8-amino-acid motif [1]. Here we examine
      the biological significance of this interaction. Inactivation of the PCNA-binding
      site of DNA ligase I had no effect on its catalytic activity or its interaction
      with DNA polymerase beta. In contrast, the loss of PCNA binding severely
      compromised the ability of DNA ligase I to join Okazaki fragments. Thus, the
      interaction between PCNA and DNA ligase I is not only critical for the subnuclear
      targeting of the ligase, but also for coordination of the molecular transactions
      that occur during lagging-strand synthesis. A functional PCNA-binding site was
      also required for the ligase to complement hypersensitivity of the DNA ligase I
      mutant cell line 46BR.1G1 to monofunctional alkylating agents, indicating that a
      cytotoxic lesion is repaired by a PCNA-dependent DNA repair pathway. Extracts
      from 46BR.1G1 cells were defective in long-patch, but not short-patch, base
      excision repair (BER). Our results show that the interaction between PCNA and DNA
      ligase I has a key role in long-patch BER and provide the first evidence for the
      biological significance of this repair mechanism.

PMID- 10959840
TI  - DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in
      chromatin condensation during apoptotic execution.
AB  - Apoptotic execution is characterized by dramatic changes in nuclear structure
      accompanied by cleavage of nuclear proteins by caspases (reviewed in [1]). Cell
      free extracts have proved useful for the identification and functional
      characterization of activities involved in apoptotic execution [2-4] and for the
      identification of proteins cleaved by caspases [5]. More recent studies have
      suggested that nuclear disassembly is driven largely by factors activated
      downstream of caspases [6]. One such factor, the caspase-activated DNase,
      CAD/CPAN/DFF40 [4,7,8] (CAD) can induce apoptotic chromatin condensation in
      isolated HeLa cell nuclei in the absence of other cytosolic factors [6,8]. As
      chromatin condensation occurs even when CAD activity is inhibited, however, CAD
      cannot be the sole morphogenetic factor triggered by caspases [6]. Here we show
      that DNA topoisomerase IIalpha (Topo IIalpha), which is essential for both
      condensation and segregation of daughter chromosomes in mitosis [9], also
      functions during apoptotic execution. Simultaneous inhibition of Topo IIalpha and
      caspases completely abolishes apoptotic chromatin condensation. In addition, we
      show that CAD binds to Topo IIalpha, and that their association enhances the
      decatenation activity of Topo IIalpha in vitro.

PMID- 10959841
TI  - Interactions of the chemotaxis signal protein CheY with bacterial flagellar
      motors visualized by evanescent wave microscopy.
AB  - The chemotaxis signal protein CheY of enteric bacteria shuttles between
      transmembrane methyl-accepting chemotaxis protein (MCP) receptor complexes and
      flagellar basal bodies [1]. The basal body C-rings, composed of the FliM, FliG
      and FliN proteins, form the rotor of the flagellar motor [2]. Phosphorylated CheY
      binds to isolated FliM [3] and may also interact with FliG [4], but its binding
      to basal bodies has not been measured. Using the chemorepellent acetate to
      phosphorylate and acetylate CheY [5], we have measured the covalent-modification
      dependent binding of a green fluorescent protein-CheY fusion (GFP-CheY) to motor
      assemblies in bacteria lacking MCP complexes by evanescent wave microscopy [6].
      At acetate concentrations that cause solely clockwise rotation, GFP-CheY
      molecules bound to native basal bodies or to overproduced rotor complexes with a
      stoichiometry comparable to the number of C-ring subunits. GFP-CheY did not bind
      to rotors lacking FIiM/FliN, showing that these subunits are essential for the
      association. This assay provides a new means of monitoring protein-protein
      interactions in signal transduction pathways in living cells.

PMID- 10959842
TI  - The scabrous protein can act as an extracellular antagonist of notch signaling in
      the Drosophila wing.
AB  - Notch (N) is a receptor for signals that inhibit neural precursor specification
      [1-6]. As N and its ligand Delta (DI) are expressed homogeneously, other
      molecules may be differentially expressed or active to permit neural precursor
      cells to arise intermingled with nonneural cells [7,8]. During Drosophila wing
      development, the glycosyltransferase encoded by the gene fringe (fng) promotes N
      signaling in response to DI, but inhibits N signaling in response to Serrate
      (Ser), which encodes a ligand that is structurally similar to DI. Dorsal
      expression of Fng protein localizes N signaling to the dorsoventral (DV) wing
      margin [9-11]. The secreted protein Scabrous (Sca) is a candidate for modulation
      of N in neural cells. Mutations at the scabrous (sca) locus alter the locations
      where precursor cells form in the peripheral nervous system [12,13]. Unlike
      fringe, sca mutations act cell non-autonomously [12]. Here, we report that
      targeted misexpression of Sca during wing development inhibited N signaling,
      blocking expression of all N target genes. Sca reduced N activation in response
      to DI more than in response to Ser. Ligand-independent signaling by
      overexpression of N protein, or by expression of activated truncated N molecules,
      was not inhibited by Sca. Our results indicate that Sca can act on N to reduce
      its availability for paracrine and autocrine interactions with DI and Ser, and
      can act as an antagonist of N signaling.

PMID- 10959843
TI  - The binding of visual patterns in bumblebees.
AB  - Bees navigating between their nests and foraging sites rely on their ability to
      learn and to recall many complex visual patterns [1-4]. How are the elements that
      make up one of these patterns bound together so that the whole pattern can be
      recalled when it is required? Consider the sentence: 'Dons nod off.' The words in
      it can be distinguished by the pattern of elements or letters that they contain.
      Words may contain the same elements arranged in different orders (don, nod), or
      contain elements of different types, or vary in both these respects (nod, off).
      We show here that bumblebees (Bombus terrestris) can learn to group the elements
      of a pattern together, such that different identifiable patterns contain the same
      elements in different combinations--analogous to the grouping of letters found in
      words. Our results suggest that pattern binding in bees is achieved in part by
      linking pattern elements directly together and in part by associating the
      elements with cues that are related to the context in which the pattern is seen.

PMID- 10959844
TI  - Functional InsP3 receptors that may modulate excitation-contraction coupling in
      the heart.
AB  - The roles of the Ca2+-mobilising messenger inositol 1,4,5-trisphosphate (InsP3)
      in heart are unclear, although many hormones activate InsP3 production in
      cardiomyocytes and some of their inotropic, chronotropic and arrhythmogenic
      effects may be due to Ca2+ release mediated by InsP3 receptors (InsP3Rs) [1-3].
      In the present study, we examined the expression and subcellular localisation of
      InsP3R isoforms, and investigated their potential role in modulating excitation
      contraction coupling (EC coupling). Western, PCR and InsP3-binding analysis
      indicated that both atrial and ventricular myocytes expressed mainly type II
      InsP3Rs, with approximately sixfold higher levels of InsP3Rs in atrial cells. Co
      immunostaining of atrial myocytes with antibodies against type II ryanodine
      receptors (RyRs) and type II InsP3Rs revealed that the latter were arranged in
      the subsarcolemmal space where they largely co-localised with the junctional
      RyRs. Stimulation of quiescent or electrically paced atrial myocytes with a
      membrane-permeant InsP3 ester, which enters cells and directly activates InsP3Rs,
      caused the appearance of spontaneous Ca2+-release events. In addition, in paced
      cells, the InsP3 ester evoked an increase in the amplitudes of action potential
      evoked Ca2+ transients. These data indicate that atrial cardiomyocytes express
      functional InsP3Rs, and that these channels could modulate EC coupling.

PMID- 10959845
TI  - split ends, a new component of the Drosophila EGF receptor pathway, regulates
      development of midline glial cells.
AB  - Signaling by DER, the Drosophila epidermal growth factor receptor tyrosine kinase
      (RTK), is essential for proper migration and survival of midline glial cells
      (MGCs) in the embryonic central nervous system (CNS) [1-4]. We recently isolated
      a gene called split ends (spen) in a screen designed to identify new components
      of the RTK/Ras pathway [5]. Drosophila Spen and its orthologs are characterized
      by a distinct set of RNA recognition motifs (RRMs) and a SPOC domain, a highly
      conserved carboxy-terminal domain of unknown function [5-7]. To investigate spen
      function in the context of RTK signaling, we examined the consequences of spen
      loss-of-function mutations on embryonic CNS development. We found that spen was
      required for normal migration and survival of MGCs and that embryos lacking spen
      had CNS defects strikingly reminiscent of those seen in mutants of several known
      components of the DER signaling pathway. In addition, spen interacted
      synergistically with the RTK effector pointed. Using MGC-targeted expression, we
      found that increased Ras signaling rescued the lethality associated with
      expression of a dominant-negative spen transgene. Therefore, spen encodes a
      positively acting component of the DER/Ras signaling pathway.

PMID- 10959847
TI  - Synthesis of new two-photon absorbing fluorene derivatives via Cu-mediated
      Ullmann condensations
AB  - The Ullmann amination reaction was utilized to provide access to a number of
      fluorene analogues from common intermediates, via facile functionalization at
      positions 2, 7, and 9 of the fluorene ring. Through variation of amine or
      iodofluorene derivative, analogues bearing substitutents with varying electron
      donating and electron-withdrawing ability, e.g., diphenylamino, bis-(4
      methoxyphenyl)amine, nitro, and benzothiazole, were synthesized in good yield.
      The novel fluorene derivatives were fully characterized, including absorption and
      emission spectra. Didecylation at the 9-position afforded remarkably soluble
      derivatives. Target compounds 4, 5, and 9 are potentially useful as fluorophores
      in two-photon fluorescence microscopy. Their UV-vis spectra display desirable
      absorption in the range of interest suitable for two-photon excitation by near-IR
      femtosecond lasers. Preliminary measurements of two-photon absorption indicate
      the derivatives exhibit high two-photon absorptivity, affirming their potential
      as two-photon fluorophores. For example, using a 1,210 nm femtosecond pump beam,
      diphenylaminobenzothiazolylfluorene 4 exhibited nondegenerate two-photon
      absorption, with two-photon absorptivity (delta) of ca. 820 x 10(-50) cm(4) s
      photon(-1) molecule(-1) at the femtosecond white light continuum probe wavelength
      of 615 nm.

PMID- 10959846
TI  - Cyk3, a novel SH3-domain protein, affects cytokinesis in yeast.
AB  - Cytokinesis requires the wholesale reorganization of the cytoskeleton and
      secretion to complete the division of one cell into two. In the budding yeast
      Saccharomyces cerevisiae, the IQGAP-related protein Iqg1 (Cyk1) promotes
      cytokinetic actin ring formation and is required for cytokinesis and viability [1
      3]. As the actin ring is not essential for cytokinesis or viability, Iqg1 must
      act by another mechanism [4]. To uncover this mechanism, a screen for high-copy
      suppressors of the iqg1 lethal phenotype was performed. CYK3 suppressed the
      requirement for IQG1 in viability and cytokinesis without restoration of the
      actin ring, demonstrating that CYK3 promotes cytokinesis through an actomyosin
      ring-independent pathway. CYK3 encodes a novel SH3-domain protein that was found
      in association with the actin ring and the mother-bud neck. cyk3 null cells had
      misshapen mother-bud necks and were deficient in cytokinesis. In the cyk3 null
      strain, actin rearrangements associated with cytokinesis appeared normal,
      suggesting that the phenotype reflects a defect in secretory targeting or septal
      synthesis. Deletion of either cyk3 or hof1 alone results in a mild cytokinetic
      phenotype [5-7], but deletion of both genes resulted in lethality and a complete
      cytokinetic block, suggesting overlapping function. Thus, Cyk3 appears to be
      important for cytokinesis and acts potentially downstream of Iqg1.

PMID- 10959848
TI  - Illudalane sesquiterpenoids from the soft coral Alcyonium paessleri: the first
      natural nitrate esters.
AB  - Fifteen illudalane sesquiterpenoids, alcyopterosins A-O (1-15) have been isolated
      from the subAntarctic soft coral Alcyonium paessleri which was collected at a
      depth of 200 m near the South Georgia Islands, and their structures were
      elucidated by spectroscopic techniques. Eight of these compounds (2, 3, 5-8, 10,
      and 13) are the first natural nitrate esters, while the other four (1, 4, 11, and
      12) are chlorinated. These compounds are as well the first illudalane
      sesquiterpenoids to be isolated from the marine environment. Compounds 1, 3, 5,
      and 8 showed mild cytotoxicity toward human tumor cell lines.

PMID- 10959849
TI  - A novel catalytic and highly enantioselective approach for the synthesis of
      optically active carbohydrate derivatives.
AB  - A catalytic enantioselective inverse-electron demand hetero-Diels-Alder reaction
      of alpha,beta-unsaturated carbonyl compounds with electron-rich alkenes catalyzed
      by chiral bisoxazolines in combination with Cu(OTf)2 as the Lewis acid is
      presented. The reaction of gamma-substituted beta,gamma-unsaturated alpha-keto
      esters with vinyl ethers and various types of cis-disubstituted alkenes proceeds
      in good yield, high diastereoselectivity, and excellent enantioselectivity. The
      potential of the reaction is demonstrated by the synthesis of optically active
      carbohydrates such as spiro-carbohydrates, an ethyl beta-D-mannoside
      tetraacetate, and acetal-protected C-2-branched carbohydrates. On the basis of X
      ray crystallographic data and the absolute configuration of the products, it is
      proposed that the alkene approaches the si-face of the reacting alpha,beta
      unsaturated carbonyl functionality when coordinated to the catalyst.

PMID- 10959850
TI  - alpha-fluorinated phosphonates as substrate mimics for glucose 6-phosphate
      dehydrogenase: the CHF stereochemistry matters.
AB  - Reported is a systematic study of the "fitness" (in terms of kcat/Km) of a series
      of phosphonate mimics of glucose 6-phosphate (G6P) as unnatural substrates for
      G6P dehydrogenase from Leuconostoc mesenteroides. The four G6P analogues (9, 10,
      15a, and 15b) differ only in the degree of fluorination at the "bridging"
      phosphonate carbon. All have been synthesized from benzyl 6-O
      trifluoromethanesulfonyl-2,3,4-tri-O-benzyl beta-D-glucopyranoside (6). The
      phosphonates with bridging CH2 (9) and CF2 (10) groups are cleanly obtained by
      direct displacements with the appropriate LiX2CP(O)(OEt)2 reagents (X = H, F) in
      15 min at -78 degrees C. For the (alpha-monofluoro)alkylphosphonates (15a/b),
      homologation of 6 is achieved via lithiodithiane-mediated triflate displacement,
      followed by aldehyde unmasking [CaCO3, Hg(ClO4)2, H2O]. Addition of diethyl
      phosphite anion produces diastereomeric, (alpha-hydroxy)phosphonates 13a/b (1.4:1
      ratio) which may be readily separated by chromatography. The stereochemistry of
      the minor diastereomer was established as 7(S) via X-ray crystallographic
      structure determination of its p-bromobenzoate derivative, 16b. Treatment of the
      major 7(R) diastereomer with DAST produces alpha-fluorinated phosphonate 14a, in
      modest yield, with inversion of configuration, as established, again, by X-ray
      crystallography. To our knowledge, this is first example of DAST-mediated
      fluorination of a (nonbenzylic, nonpropargylic) secondary (alpha
      hydroxy)phosphonate and thus establishes the stereochemical course of this
      transformation. alpha-Deprotonation/kinetic quenching of 14a provides access to
      the 7(R)-epimer (14b). For all four protected phosphonates (7, 8, 14a, and 14b),
      diethyl phosphonate ester deprotection was carried out with TMSBr, followed by
      global hydrogenolytic debenzylation to produce the free phosphonates, as
      alpha/beta anomeric mixtures. Titrations of G6P itself and the free phosphonic
      acids provides second pKa values of 6.5 (1, bridging-O), 5.4 (10, bridging-CF2),
      6.2 (14a, bridging-CHF), and 7.6 (9, bridging-CH2). Leuconostoc mesenteroides
      G6PDH-mediated oxidation and Lineweaver-Burk analysis yields normalized kcat/Km
      values of 0.043 (14b, bridging-7(R)-CHF), 0.11 (10, bridging-CF2), 0.23 (14b,
      bridging-CH2), and 0.46 (14a, bridging-7(S)-CHF) relative to G6P itself, largely
      reflecting differences in Km. The fact that kcat/Km increases by more than an
      order of magnitude in going from the 7(R)-alpha-monofluoroalkyl phosphonate
      (worst substrate) to the 7(S)-diastereomer (best substrate) is especially notable
      and is discussed in the context of the known phosphate binding pocket of this
      enzyme as revealed by X-ray crystallography (Adams, M. J. et al. Structure 1994,
      2, 1073-1087).

PMID- 10959852
TI  - Enolate ions as beta-activators of ortho-metalation: direct synthesis of 3
      aminoindenones
AB  - beta-Ketonitriles derived from a Claisen condensation of benzoate esters with
      alkyl- or phenylacetonitriles lead to 3-aminoindenones in the presence of excess
      LDA. This new reaction is also applicable to pyridine carboxylic esters. All of
      the 3-aminoindenones and their aza analogues can be hydrolyzed by acid to give
      the corresponding 1,3-indandiones. The mechanism of the reaction falls into the
      directed-ortho-metalation class in which the initial enolate ion of the keto
      nitrile directs self-metalation at an ortho position. The new anion then cyclizes
      onto the nitrile group to generate an aminoindenone. Surprisingly the simplest
      member of the series, benzoylacetonitrile, does not undergo cyclization.
      Mechanistic isotope studies revealed that this substance preferentially and
      directly forms a dianion on the side chain, which is not further deprotonated at
      the ortho position of the aromatic ring.

PMID- 10959851
TI  - A novel class of zinc-binding inhibitors for the phosphatidylcholine-preferring
      phospholipase C from Bacillus cereus.
AB  - The phospholipase C (PLC) isozymes catalyze the hydrolysis of phospholipids to
      provide diacylglycerol (DAG) and a phosphorylated headgroup. Because DAG has been
      implicated in cellular signal transduction cascades in mammalian systems, there
      has been considerable interest in the development of inhibitors of these enzymes.
      Toward this end, we have discovered that the cyclic N,N'-dihydroxyureas 6-10
      inhibit the phosphatidylcholine preferring PLC from Bacillus cereus (PLCBc). This
      class of inhibitors is believed to function by the bidentate chelation of the
      N,N'-dihydroxyurea array to one or more of the zinc ions at the active site of
      the enzyme. Because the affinities of these compounds correlate with the pKaS of
      the N-OH hydroxyl groups, it is apparent that one or both of the hydroxyl groups
      must be ionized for effective coordination to the zinc ions. It is also apparent
      that there may be rather strict steric requirements for these inhibitors.

PMID- 10959853
TI  - Stereoselective synthesis of cyclic ethers using vinylogous sulfonates as radical
      acceptors: effect of E/Z geometry and temperature on diastereoselectivity.
AB  - Treatment of the E-vinylogous sulfonates 1a-g with tris(trimethylsilyl)silane and
      triethylborane, in the presence of air, furnished the cyclic ethers 2/3a-g with
      good to excellent diastereoselectivity favoring the cis-isomer 2. This study
      demonstrated the level of stereocontrol in a 6-exo radical cyclization and may be
      attributed to the type of radical intermediate. Hence, the modest selectivity
      obtained for the cyclization of 1e may be a function of the acyl radical geometry
      (sp2) and high inversion barrier (29 kcal/mol) as compared to the alkyl (1
      kcal/mol) and vinyl (2.9 kcal/mol) radicals. This is consistent with the acyl
      radical cyclization having an earlier transition state than the corresponding
      alkyl and vinyl radicals. The modest diastereoselectivity can be improved
      dramatically using the Z-vinylogous sulfonate (> or =34:1; R = Ph) to promote
      kinetic trapping of the s-trans rotamer I and III, respectively (Figure 1). The 5
      exo alkyl radical cyclization reaction under nonreductive Keck-allylation
      conditions was also examined, in which 8 was formed in 91% overall yield. This
      transformation provides a convenient method for in situ homologation and should
      be applicable to target directed synthesis.

PMID- 10959854
TI  - Chemoenzymatic synthesis of the microbial elicitor (-)-syringolide via a fructose
      1,6-diphosphate aldolase-catalyzed condensation reaction.
AB  - Syringolide 2, an elicitor of the bacterial plant pathogen Pseudomonas syringae
      pv. tomato which triggers a hypersensitive defense response in resistant soybean
      plants, has been synthesized in five steps via a fructose 1,6-diphosphate
      aldolase reaction.

PMID- 10959855
TI  - Effect of protic cosolvents on the photooxygenation of diethyl sulfide
AB  - The sluggish (kr < 10kq) photooxygenation of diethyl sulfide in both benzene and
      other aprotic solvents such as acetone and acetonitrile is made efficient by
      addition of small amounts of alcohols and, with a much more conspicuous increase,
      of phenols and carboxylic acids (<<0.1% additive is sufficient in this case). A
      kinetic analysis shows that the effect is accounted for by interaction of the
      protic additives with the first formed intermediate, the persulfoxide, in
      competition with cleavage to the components. The thus obtained rate constants kH
      linearly correlate with the acid strength of the additives, and the effect is
      rationalized as a general acid catalysis. Hydrogen bonding of the persulfoxide
      under this condition accounts in an economic way for the observed data, including
      co-oxygenation of Ph2SO in mixed solvents.

PMID- 10959856
TI  - Highly selective palladium-catalyzed synthesis of protected alpha,beta
      unsaturated methyl ketones and 2-alkoxy-1,3-butadienes. High-speed chemistry by
      microwave flash heating
AB  - A selective and mild procedure is described for the direct synthesis of 2-alkene
      2-methyl-1,3-dioxolanes via regiocontrolled Heck vinylation of commercially
      available 2-hydroxyethyl vinyl ether. The procedure permits chemoselective
      transformation of a vinylic triflate or bromide into a blocked alpha,beta
      unsaturated methyl ketone. Furthermore, a significantly improved and highly
      regioselective synthesis of 2-alkoxy-1,3-butadienes has been developed. Flash
      heating by microwave irradiation promotes the palladium-catalyzed reactions, and
      the starting materials are fully converted after reaction times of 5-7 min.

PMID- 10959857
TI  - A convenient new route to piperidines, pyrrolizidines, indolizidines, and
      quinolizidines by cyclization of acetylenic sulfones with beta and gamma
      chloroamines. Enantioselective total synthesis of indolizidines (-)-167B, (-)
      209D, (-)-209B, and (-)-207A.
AB  - The methyl esters of (L)-phenylalanine and (L)-methionine underwent conjugate
      additions via their free amino groups to 1-(p-toluenesulfonyl)hexyne, followed by
      intramolecular acylation of the corresponding enamide anions and tautomerization
      to afford 2-benzyl-5-n-butyl-3-hydroxy-4-(p-toluenesulfonyl)pyrrole and 5-n-butyl
      3-hydroxy-2-(2-methylthioethyl)-4-(p-toluenesulfonyl)pyr role, respectively. The
      conjugate additions of a series of acyclic and cyclic secondary beta- and gamma
      chloroamines to acetylenic sulfones proceeded similarly under mild conditions.
      The resulting adducts were deprotonated with LDA in THF at -78 degrees C, and the
      resulting sulfone-stabilized carbanions underwent intramolecular alkylation to
      afford cyclic enamine sulfones. Thus, acyclic gamma-chloroalkyl-benzylamines
      afforded the corresponding 2- or 2,6-disubstituted piperidines, while 2
      (chloromethyl)pyrrolidines, 2-(2-chloroethyl)pyrrolidines, 2
      (chloromethyl)piperidines, and 2-(2-chloroethyl)piperidines produced the
      corresponding 3-substituted pyrrolizidines, 5- or 3-substituted indolizidines,
      and 4-substituted quinolizidines, respectively. 8-Methyl-5-substituted
      indolizidines were also prepared from the appropriate methyl-substituted
      chloroamine precursor. Enantioselective syntheses were achieved by employing
      chiral chloroamines derived from amino acids or other enantiopure precursors.
      Further transformations of several of the products provided concise syntheses of
      four dendrobatid alkaloids. Thus, reduction of (8aS)-5-n-propyl-6-(p
      toluenesulfonyl)-delta5,6-indolizidine with sodium cyanoborohydride in
      trifluoroacetic acid, followed by reductive desulfonylation, afforded (-)
      indolizidine 167B. The corresponding 5-n-hexyl derivative similarly produced (-)
      indolizidine 209D, while (-)-(8R, 8aS)-8-methyl-5-n-pentyl-6-(p-toluenesulfonyl)
      delta5,6-indo lizidine furnished (-)-indolizidine 209B. Finally, the similar
      reduction and debenzylation of (-)-(8R,8aS)-5-(2-benzyloxyethyl)-8-methyl-6-(p
      toluenesulfo nyl)-delta5,6-indolizidine produced the corresponding 5-hydroxyethyl
      indolizidine. This was subjected to chlorination of the alcohol group with
      thionyl chloride and substitution with a higher order allyl cuprate reagent to
      afford (-)-indolizidine 207A.

PMID- 10959858
TI  - A novel route to the vinyl sulfide nine-membered macrocycle moiety of
      Griseoviridin.
AB  - The synthetic potentialities of cerium(III) chloride are demonstrated by the
      synthesis of a nine-membered ring heterocycle component of Griseoviridin (3) in
      optically active form. The key step involves the stereospecific formation of the
      alpha-carbalkoxy alkenyl sulfide moiety using a combination system of cerium(III)
      chloride heptahydrate and sodium iodide.

PMID- 10959859
TI  - P(MeNCH2CH2)3N: a highly selective reagent for synthesizing trans-epoxides from
      aryl aldehydes
AB  - In contrast to its acyclic analogue P(NMe2)3 (1), which in benzene at room
      temperature reacts with two aryl aldehyde molecules bearing electron-withdrawing
      groups to give the corresponding diaryl epoxide as an isomeric mixture (trans/cis
      ratios: 72/28-51/49), P(MeNCH2CH2)3N (2a) under the same reaction conditions is
      found to be a highly selective reagent that provides epoxides with trans/cis
      ratios as high as 99/1. These reactions are faster with 2a, because its
      phosphorus atom is apparently more nucleophilic than that in 1. Thus, it is found
      that 2a more easily forms 1:1 and 1:2 adducts with one or two molecules of
      aldehyde, respectively. These adducts apparently are intermediates in the
      formation of the product epoxide and the corresponding phosphine oxides of 1 and
      2a.

PMID- 10959860
TI  - Total syntheses of (-)-methyl atis-16-en-19-oate, (-)-methyl kaur-16-en-19-oate,
      and (-)-methyl trachyloban-19-oate by a combination of palladium-catalyzed
      cycloalkenylation and homoallyl-homoallyl radical rearrangement.
AB  - Asymmetric total syntheses of (-)-methyl atis-16-en-19-oate (1c), (-)-methyl kaur
      16-en-19-oate (2c), and (-)-methyl trachyloban-19-oate (3c) have been achieved by
      employing a hybrid strategy of palladium-catalyzed cycloalkenylation and
      homoallyl-homoallyl radical rearrangement. The common synthetic intermediate 5
      was prepared from 2-allylcyclohexanone (4) with 98% ee using d'Angelo's
      asymmetric Michael addition. A series of functional group modifications in 5 via
      palladium-catalyzed cycloalkenylation led to (+)-14, which had already been
      prepared by us as racemate. (-)-Methyl atis-16-ene-19-oate (1c) was generated via
      homoallyl-homoallyl radical rearrangement. On the other hand, Wolff-Kishner
      reduction of 18 followed by esterification yielded (-)-methyl kaur-16-en-19-oate
      (2c) together with (-)-methyl trachyloban-19-oate (3c).

PMID- 10959861
TI  - An efficient preparation of vinamidinium hexafluorophosphate salts.
AB  - Substituted acetic acids or acetyl chlorides react with phosphorus oxychloride in
      DMF to yield the vinamidinium salts 3a-j in moderate to excellent recrystallized
      yields (28-90%). The cations are conveniently isolated as their
      hexafluorophosphate salts, which are easily handled nonhygroscopic solids. The
      nitro compound 3l is prepared in 91% yield by nitration of the parent
      vinamidinium 3k. The X-ray crystal structure is reported for the 2-phenyl isomer
      3e and displays minimal overlap of the two pi-systems.

PMID- 10959862
TI  - Nickel-catalyzed electrochemical couplings of vinyl halides: synthetic and
      stereochemical aspects
AB  - Homo- and cross-coupling involving alkenyl halides have been performed
      efficiently using an electroassisted nickel-complex catalysis. Valuable product
      such as conjugated dienes, beta,gamma- or gamma,delta-unsaturated esters,
      ketones, or nitriles, as well as alkenylated aryl compounds are thus prepared
      with high yields and high stereoselectivity. Partial isomerization is only
      observed in a few cases, when the alkenyl halide is involved in a late step of
      the catalytic cycle. This is the case in the preparation of (Z,Z)-1,3-diene.

PMID- 10959863
TI  - Long-range sigma-pi interactions in tetrahydro-4H-thiopyran end-capped
      oligo(cyclohexylidenes). Photo-electron spectroscopy, ab initio SCF MO
      calculations, and natural bond orbital analyses
AB  - Long-range sigma-pi interactions in tetrahydro4H-thiopyran end-capped
      oligo(cyclohexylidenes) were identified by He(I) photoelectron spectroscopy (PES)
      and ab initio RHF/6-31G* calculations. The vertical ionization energies Ivj of
      the highest occupied molecular orbitals (MO's) were assigned using Koopmans'
      theorem (Iv,j = -epsilonj) and by correlation with the ionizations of related
      reference compounds. The experimental (PES) and theoretical (RHF/6-31G*) results
      are in good agreement. For tercyclohexylidene derivatives which contain two
      nonconjugated pi-bonds splittings deltaIv,j of the pi-bands in the range from
      approximately 0.5 to 0.7 eV (delta-epsilonj approximately 0.6 to 0.9 eV). For the
      bi- and tercyclohexylidene compounds containing two sulfur atoms at their alpha-
      and omega-end positions the pi-type sulfur lone pair bands [Lppi(S)] split
      significantly by deltaIvj approximately 0.3 to 0.4 eV (delta-epsilonj
      approximately 0.3 to 0.4 eV), i.e. sigma-pi interactions over distances of ca. 8
      and 12 A, respectively, occur. The magnitude of the interactions and the observed
      splittings are independent of the anti and syn conformations of the
      oligo(cyclohexylidene) hydrocarbon skeletons. RHF/6-31G* Natural Bond Orbital
      analyses reveal that the Hax-C-C-Hax precanonical MO's (PCMO's) centered on the
      cyclohexyl-type rings are paramount for the relay of the through-bond sigma-pi
      interactions; no through-space sigma-pi interactions were identified.

PMID- 10959864
TI  - Enantioselective Michael reactions of chiral secondary enaminoesters with 2
      substituted nitroethylenes. Syntheses of trans, trans-2,4-disubstituted
      pyrrolidine-3-carboxylates
AB  - The Michael reaction of chiral 3-substituted secondary enaminoesters with 2
      substituted nitroethylenes leads to (Z)-adducts, with good to excellent
      diastereoselectivity. The nitro group of these adducts was catalytically reduced
      to give, after cyclization and chiral amine elimination, pyrrolines or
      pyrrolidines after further reduction. In particular, the syntheses of ethyl
      (2R,3S,4S)-2,4-dimethylpyrrolidine-3-carboxylate and ethyl (2R,3R,4S)-2-(4
      methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-carboxylate are
      described.

PMID- 10959865
TI  - 20-O-acylcamptothecin derivatives: evidence for lactone stabilization.
AB  - Convincing UV and NMR spectrophotometric evidence is presented which demonstrates
      that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are
      substantially more stable in the lactone form than the 20-OH parent.
      Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O
      ether derivative of CPT underwent endocyclic ring opening at pH > or =8.5, while
      the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other
      smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which
      arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl
      PEG (or alkyl) carboxylate forms.

PMID- 10959866
TI  - Synthesis of thio-linked disaccharides by 1-->2 intramolecular thioglycosyl
      migration: oxacarbenium versus episulfonium ion intermediates.
AB  - The conversion of 1,1'-thio-linked glucopyranosyl alpha-D-mannopyranosides to 1,2
      thio-linked methyl sophorosides or methyl kojibiosides is described. The method
      involves the 1-->2-migration of the thioglucopyranosyl portion of the nonreducing
      disaccharide with inversion of configuration at C-2 of the mannopyranose ring and
      concomitant formation of the methyl glucopyranoside. The thioglucosyl migration
      does not occur when electron-withdrawing benzoate protecting groups are present.
      The rearrangement occurs with retention of configuration in the migrating
      thioglucoside but the methyl glycoside is formed as a mixture of alpha- and beta
      isomers. This is attributed to a mechanism involving an oxacarbenium-ion
      intermediate rather than an episulfonium-ion intermediate. The relevance of this
      work to recent theoretical predictions concerning the relative stability of such
      intermediates is discussed.

PMID- 10959867
TI  - Preparation of new polyfunctional magnesiated heterocycles using a chlorine-,
      bromine-, or iodine-magnesium exchange
AB  - The reaction of heteroaryl iodides with i-PrMgBr (ca. 1.0 equiv) in THF provides
      the corresponding magnesiated heterocycles. Functional groups such as an ester,
      cyano, or chloride functions are tolerated in these new Grignard reagents if the
      exchange can be performed below -20 degrees C. This is the case for all
      heterocycles bearing electron-withdrawing groups or chelating functions
      facilitating the iodine-magnesium exchange. In many cases, the exchange can be
      extended to heteroaryl bromides, and a case of a chlorine-magnesium exchange is
      described with tetrachlorothiophene. This new preparation of functionalized
      heteroarylmagnesium compounds provides after reaction with various electrophiles
      a new entry to a broad range of polyfunctional pyridines, imidazoles, furanes,
      thiophenes, pyrroles, antipyrines, and uracil derivatives. The application of the
      halogen-magnesium exchange in the solid phase allows the performance of solid
      phase synthesis, with potential applications for combinatorial chemistry.

PMID- 10959868
TI  - Gas-phase basicity of polyfunctional amidinazines: experimental evidence of
      preferred site(s) of protonation
AB  - Gas-phase basicities of four polyfunctional N1,N1-dimethyl-N2-azinylformamidines
      (1-4) are obtained from proton-transfer equilibrium constant determinations,
      using Fourier transform ion-cyclotron resonance mass spectrometry. Comparison
      with model amidines and azines (GB revised according to the recent compilation of
      Hunter and Lias) indicates the aza group as the favored site of protonation. The
      strong basicity of ortho derivatives is explained in term of intramolecular
      stabilization (the so-called "internal solvation").

PMID- 10959869
TI  - Stereoelectronic effect on one-electron reductive release of 5-fluorouracil from
      5-fluoro-1-(2-oxocycloalkyl)uracils as a new class of radiation-activated
      antitumor prodrugs.
AB  - A series of 5-fluoro-1-(2'-oxocycloalkyl)uracils (3-11) that are potentially
      novel radiation-activated prodrugs for the radiotherapy of hypoxic tumor cells
      have been synthesized to evaluate a relationship between the molecular structure
      and the reactivity of one-electron reductive release of antitumor 5-fluorouracil
      (1) in anoxic aqueous solution. All the compounds 3-11 bearing the 2'-oxo group
      were one-electron reduced by hydrated electrons (eaq-) and thereby underwent
      C(1')-N(1) bond dissociation to release 5-fluorouracil 1 in 47-96% yields upon
      radiolysis of anoxic aqueous solution, while control compounds (12, 13) without
      the 2'-oxo substituent had no reactivity toward such a reductive C(1')-N(1) bond
      dissociation. The decomposition of 2-oxo compounds in the radiolytic one-electron
      reduction was more enhanced, as the one-electron reduction potential measured by
      cyclic voltammetry in N,N-dimethylformamide became more positive. The efficiency
      of 5-fluorouracil release was strongly dependent on the structural flexibility of
      2-oxo compounds. X-ray crystallographic studies of representative compounds
      revealed that the C(1')-N(1) bond possesses normal geometry and bond length in
      the ground state. MO calculations by the AM1 method demonstrated that the LUMO is
      primarily localized at the pi* orbital of C(5)-C(6) double bond of the 5
      fluorouracil moiety, and that the LUMO + 1 is delocalized between the pi* orbital
      of 2'-oxo substituent and the sigma* orbital of adjacent C(1')-N(1) bond. The one
      electron reductive release of 5-fluorouracil 1 in anoxic aqueous solution was
      presumed to occur from the LUMO + 1 of radical anion intermediates possessing a
      partial mixing of the antibonding C(2')=O pi* and C(1')-N(1) sigma* MO's, that
      may be facilitated by a dynamic conformational change to achieve higher degree of
      (pi* + sigma*) MO mixing.

PMID- 10959871
TI  - Molecular addition compounds. 16. New, highly reactive borane adducts with N,N
      dialkyl-tert-alkylamines for hydroboration
AB  - Several N,N-diethyl-tert-alkylamines, such as N,N-diethyl-2-methyl-2-butylamine
      (1, t-PentNEt2), N,N-diethyl-2,3-dimethyl-2-butylamine (2, t-HexNEt2), N,N
      diethyl-2,3,3-trimethyl-2-butylamine (3, t-HeptNEt2), and N,N-diethyl-1,1,3,3
      tetramethylbutylamine (4, t-OctNEt2) with varying steric bulk around nitrogen (by
      changing the tert-alkyl group) have been prepared and examined as borane
      carriers. The complexing ability of these N,N-diethyl-tert-alkylamines with
      borane decreases in the order: t-BuNEt2 > t-PentNEt2 > t-HeptNEt2 > t-HexNEt2 >
      or = t-OctNEt2. From these preliminary studies, the more promising tert
      octyldialkylamines were selected for detailed studies. The optimum steric bulk
      around the nitrogen atom was established by comparing various tert
      octyldialkylamines containing variable steric requirements for both the alkyl
      groups. The complexing ability of these amines with borane decreases in the order
      shown: t-OctNMe2 (5) > t-OctNEtMe (6) > t-OctN-(CH2CH2)2O (7) > t-OctNEt2 (4) > t
      OctNBuiMe (8) > t-OctNPr(n)2 (9). The reactivity of the corresponding borane
      adducts toward 1-octene increases in the reverse order. Among the various tert
      octyldialkylamine-boranes prepared and examined, only t-OctNEt2 (4) forms a
      highly reactive liquid borane adduct, which hydroborates 1-octene in
      tetrahydrofuran rapidly at room temperature. Accordingly, detailed hydroboration
      studies with this new, highly reactive amine-borane adduct, t-OctEt2N:BH3 (10)
      and representative mono-, di-, tri-, and tetra-substituted olefins were carried
      out at room temperature (22 +/- 3 degrees C) in selected solvents,
      tetrahydrofuran, dioxane, tert-butyl methyl ether, n-pentane and dichloromethane.
      Simple unhindered olefins were hydroborated to the trialkylborane stage, whereas
      hindered olefins were partially hydroborated to the mono or dialkylborane stage.
      The hydroborations can be carried out conveniently in a variety of solvents. The
      amine-borane adduct showed enhanced reactivity in dioxane but low reactivity in
      dichloromethane. The alkylboranes obtained after hydroboration were oxidized with
      hydrogen peroxide/sodium hydroxide and the product alcohols were obtained in
      quantitative yields, as established by GC analysis. The carrier amine was
      recovered by simple acid-base manipulations in good yield and can be readily
      recycled back to the borane adduct.

PMID- 10959870
TI  - Independent generation and reactivity of 2-deoxy-5-methyleneuridin-5-yl, a
      significant reactive intermediate produced from thymidine as a result of
      oxidative stress.
AB  - 2'-Deoxy-5-methyleneuridin-5-yl (1) is produced in a variety of DNA damage
      processes and is believed to result in the formation of lesions that are
      mutagenic and refractory to enzymatic repair. 2'-Deoxy-5-methyleneuridin-5-yl (1)
      was independently generated under anaerobic conditions via Norrish Type I
      photocleavage during Pyrex filtered photolysis of the benzyl ketone 7. The
      radical (1) exhibits behavior consistent with that of a resonance-stabilized
      radical. The KIE for hydrogen atom transfer from t-BuSH was found to be 7.3 +/-
      1.7. Competition studies between radical recombination and hydrogen atom donors
      (2,5-dimethyltetrahydrofuran, kTrap = 46.1 +/- 15.4 M(-1) s(-1); propan-2-ol,
      kTrap = 13.6 +/- 3.5 M(-1) s(-1)) chosen to mimic the carbohydrate components of
      2'-deoxyribonucleotides suggest that 2'-deoxy-5-methyleneuridin-5-yl (1) may be
      able to transfer damage from the nucleobase to the deoxyribose of an adjacent
      nucleotide in DNA under hypoxic conditions.

PMID- 10959872
TI  - Keto<==>enol, imine<==>enamine, and nitro<==>aci-nitro tautomerism and their
      interrelationship in substituted nitroethylenes. Keto, imine, nitro, and vinyl
      substituent effects and the importance of H-bonding
AB  - Tautomeric isomers and conformers of 2-nitrovinyl alcohol (1), 2-nitrovinylamine
      (2), and 1-nitro-propene (3) are reported at the MP2 and B3LYP levels of theory,
      using the 6-31G* basis set, with energy evaluation at B3LYP/6-311+G** and G2MP2.
      The nitroalkenes are the global minima on their respective potential energy
      surfaces. The barriers for the concerted 1,5-H transfer to the corresponding
      nitronic acids amount to only 5.0 kcal/mol for 1, 13.2 kcal/mol for 2, and a
      sizable 37.8 kcal/mol for 3. Whereas the aci-nitro tautomer of 2-nitrovinyl
      alcohol is easily accessible, beta-iminonitronic acid has little kinetic
      stability. H-bonding is a strong stabilizing factor in these nitroalkenes,
      estimated at 7.0 and 3.7 kcal/mol for the OH and NH2 derivatives, respectively,
      while its stabilization in their nitronic acids amounts to as much as 13
      kcal/mol. The H-bonds are evident from the very short O...H and N...H distances
      and are characterized by bond critical points. The NO2 substituent effect of
      about 11.4 kcal/mol at G2MP2 on both the classical keto <==> enol and imine <==>
      enamine tautomeric processes stabilizes the nitroethylene derivatives. The keto,
      imine, and vinyl substituent effects at G2MP2 on the nitro <==> aci-nitro
      tautomeric process are also determined as are their pi-resonance components. The
      substituents have a large influence on the ionization energies of the
      nitroethylene derivatives.

PMID- 10959873
TI  - The [4+2]] addition of singlet oxygen to thebaine: new access to highly
      functionalized morphine derivatives via opioid endoperoxides.
AB  - The photooxidation of thebaine (3) with a sun lamp affords two main products:
      hydrodibenzofuran 10 (major) and benzofuran 11 (minor). The latter compound
      becomes predominant if a Hg lamp is used instead of a sun lamp. The formation of
      10 proceeds via an endoperoxide intermediate that undergoes oxidation at the
      nitrogen atom. Protection of the nitrogen either by protonation or quaternization
      prevents its oxidation and thus the photooxidation of 3 in acid media constitutes
      a one-pot procedure for the preparation of 14-hydroxycodeinone 35. Photooxidation
      of the thebaine ammonium salt 31 allows the isolation in good yields of the
      corresponding to thebaine endoperoxide 32. The selective protection and reduction
      of the keto, aldehyde, and olefinic groups of hydrodibenzofuran 10 allowed the
      preparation of several diol and keto alcohol derivatives. This is the first
      report on the use of photooxidation to functionalize thebaine at C(6) and C(14)
      and also the first on the isolation of opioid endoperoxides.

PMID- 10959874
TI  - Iodophosphoryloxylation of carbon-carbon multibonds and its application to
      glycals
AB  - Iodophosphoryloxylation of carbon-carbon multibonds was attempted. Alkynes and
      cyclohexene were converted to the corresponding 1,2-iodophosphoryloxylated
      compounds in moderate to good yields with a trivalent iodine compound/iodine
      system, while glucal gave mainly the corresponding iodohydrin compound in this
      system. However, 2-deoxy-2-iodoglycosyl diphenylphosphinates were obtained from
      the corresponding glycals with a diphenylphosphinic acid/iodine/potassium
      carbonate system in good yields. Moreover, triethylborane smoothly reduced 2
      deoxy-2-iodoglycosyl diphenylphosphinates to 2-deoxyglycosyl diphenylphosphinates
      in a 1,4-cyclohexadiene solvent.

PMID- 10959876
TI  - Selective deprotection of acetals with Me3SiCH2MgCl. Peterson-type olefination of
      acetals
AB  - By employing the chelation strategy, treatment of an acetal of a contiguous diol
      with Me3SiCH2MgCl liberates the corresponding diol regioselectively. In addition,
      acetals of different structural variety are transformed upon treatment with
      Me3SiCH2MgCl and ZnI2 into the corresponding olefination products in good yield.

PMID- 10959875
TI  - A biomimetic total synthesis of (-)-spirotryprostatin B and related studies.
AB  - The prenylated natural products spirotryprostatin A and B derived from the Trp
      Pro diketopiperazine also feature an oxidative rearrangement of the indole to
      form a spirooxindole. Synthetically, formation of the oxindole ring was
      stereoselectively accomplished by reaction of the appropriate indole precursor
      with N-bromosuccinimide. For optimum results, the oxidation should be carried out
      prior to diketopiperazine cyclization. In this manner, we have synthesized the
      tetrahydro- and dihydro- analogues of spirotryprostatin B in four steps from L
      tryptophan methyl ester. The dihydro derivative was then converted to
      spirotryprostatin B by unsaturation of the pyrrolidine ring to a pyrroline, thus
      unambiguously confirming the structure of the natural product.

PMID- 10959877
TI  - 1,3-dimethoxy-5-methylene-1,3-cyclohexadiene compounds with leaving groups at C6:
      generation, solvolytic reactivity, and their importance in the photochemistry of
      3,5-dimethoxybenzyl derivatives
AB  - The photochemistry of 3,5-dimethoxybenzyl compounds with the leaving groups
      acetate (1a), chloride (1b), bromide (1c), iodide (1d), diethyl phosphate (1e),
      and trimethylamine (1f), as the chloride, was examined by both product studies
      and flash photolysis. The isomeric triene, 5-methylene-1,3-cyclohexadiene
      derivative was observed for the acetate (2a), diethyl phosphate (2e) and
      trimethylammonium chloride (2f). The solvolysis of these derivatives, 2, was
      examined in alcohol solvents and the rate correlation with YOTS values gave m =
      0.47 (2a) and 0.63 (2e), suggesting SN1 reactivity but with an early transition
      state. Quantum yields for formation of 2a and 2e indicated that these trienes
      play only a minor role (approximately 16%) in the overall photochemistry of the
      corresponding arylmethyl substrates.

PMID- 10959878
TI  - Kinetics and mechanism of the pyridinolysis of phenacyl bromides in acetonitrile
AB  - Kinetic studies of the reactions of substituted phenacyl bromides (YC6H4COCH2Br)
      with pyridines (XC5H4N) are carried out in acetonitrile at 45.0 degrees C. A
      biphasic Bronsted plot is obtained with a change in slope from a large (betaX
      approximately equals 0.65-0.80) to a small (betaX approximately 0.36-0.40) value
      at pKa = 3.2-3.6, which can be attributed to a change in the rate-determining
      step from breakdown to formation of a tetrahedral intermediate in the reaction
      path as the basicity of the pyridine nucleophile increases. This mechanism is
      supported by the faster rates with pyridines than with anilines and the change of
      cross-interaction constant rhoXY from a large positive (rhoXY = +1.4) to a small
      positive (rhoXY approximately +0.1) value. The large magnitude of Hammett rhoX (=
      -5.5 to -6.9) values for the pyridines with electron-withdrawing substituents and
      positive deviations of the pi-acceptors, p-CH3CO and p-CN, are quite similar to
      those for the pyridinium ion formation equilibria. The activation parameters are
      also in line with the proposed mechanism.

PMID- 10959879
TI  - Synthetic utility and mechanistic implications of the Fries rearrangement of
      hydroquinone diesters in boron trifluoride complexes
AB  - Reactions of boron trifluoride methyl and ethyl etherate complexes with
      hydroquinone diesters yield monomethyl and monoethyl derivatives of
      acetylhydroquinones. The use of sterically hindered boron trifluoride etherate
      complexes results in acetylhydroquinone derivatives. This procedure represents a
      one-step synthesis of acetylhydroquinone derivatives, important building blocks
      for a variety of synthetic applications.

PMID- 10959880
TI  - Quenching of a photosensitized dye through single-electron transfer from
      trivalent phosphorus compounds
AB  - Various types of trivalent phosphorus compounds 1 undergo single-electron
      transfer (SET) to the photoexcited state of rhodamine 6G (Rho+*) in aqueous
      acetonitrile to quench the fluorescence from Rho+*. The rate constants kp for the
      overall SET process were determined by the Stern-Volmer method. The rate is
      nearly constant at a diffusion-controlled limit in the region of E1/2(1) < 1.3 V
      (vs Ag/Ag+), whereas log kp depends linearly on E1/2(1) in the region of E1/2(1)
      > 1.3 V, the slope of the correlation line being -alphaF/RT with alpha = 0.2. The
      potential at which the change in dependence of log kp on E1/2(1) occurs (1.3 V)
      is in accordance with the value of E1/2(Rho+*) (1.22 V) that has been obtained
      experimentally. Thus, the SET step is exothermic when E1/2(1) < 1.3 V and
      endothermic when E1/2(1) > 1.3 V. The alpha-value (0.2) obtained in the
      endothermic region shows that the SET step from 1 to Rho+* is irreversible in
      this region. Trivalent phosphorus radical cation 1*+ generated in the SET step
      undergoes an ionic reaction with water in the solvent rapidly enough to make the
      SET step irreversible. In contrast, the SET from amines 2 and alkoxybenzenes 3 to
      Rho+* is reversible when the SET step is endothermic, meaning that the radical
      cations 2*+ and 3*+ generated in the SET step undergo rapid "back SET" in the
      ground state to regenerate 2 and 3.

PMID- 10959881
TI  - The synthesis of P-chiral amino acid-derived phosphonamidic anhydrides.
AB  - The synthesis of an array of P-chiral amino acid-derived phosphonamidic
      anhydrides is described. These anhydrides are prepared by condensation of
      allylated amino acids 19-22 with methyl- or vinylphosphonic dichlorides 23 or 24
      to produce three diastereomeric anhydrides 4-11a-c in good to excellent yields.
      The mechanistic issues concerning anhydride formation are discussed and supported
      by experimental results. Vinylphosphonamidic anhydrides 8-11 are further
      derivatized via the ring-closing metathesis (RCM) reaction to yield amino acid
      derived bicyclic phosphonamidic anhydrides.

PMID- 10959882
TI  - A single step conversion of tetrahydropyranyl ethers to acetates.

PMID- 10959883
TI  - Ytterbium(III) trifluoromethanesulfonate catalyzed electrophilic aromatic
      substitution with glyoxalate and lipase-mediated product resolution: a convenient
      route to optically active aromatic alpha-hydroxy esters.

PMID- 10959884
TI  - Chiral azole derivatives. 4. Enantiomers of bifonazole and related antifungal
      agents: synthesis, configuration assignment, and biological evaluation.

PMID- 10959885
TI  - Regioselective monobenzoylation of unsymmetrical piperazines.

PMID- 10959886
TI  - The nitration of 1,3,5-triazine with dinitrogen pentoxide.
      ChafinAP@navair.navy.mil

PMID- 10959887
TI  - Z-selective Horner-Wadsworth-Emmons reaction of ethyl (diarylphosphono)acetates
      using sodium iodide and DBU

PMID- 10959888
TI  - Formation of 2,6-bis(4-chlorophenyl)-5,6-dihydro-2H-1,3,4-oxadiazine-4-oxide by
      an intramolecular amino/nitro dehydration

PMID- 10959889
TI  - Stereoselective synthesis of (1R,2S,3R)-camphordiamine.

PMID- 10959891
TI  - The reaction of 1,2-amino alcohols with carbon dioxide in the presence of 2
      pyrrolidone electrogenerated base. New synthesis of chiral oxazolidin-2-ones

PMID- 10959890
TI  - Highly diastereoselective Diels-Alder reactions using a fructose diacetonide
      chiral scaffold.

PMID- 10959892
TI  - Total synthesis of [(2S)-Hiv2]didemnin M.

PMID- 10959894
TI  - Preparation of a resin-bound cobalt phosphine complex and assessment of its use
      in catalytic oxidation and acid anhydride synthesis

PMID- 10959893
TI  - (R,R,R)-2,5-diaminocylohexanecarboxylic acid, a building block for water-soluble,
      helix-forming beta-peptides.

PMID- 10959896
TI  - A new synthetic route to P-chiral phosphine-boranes of high enantiopurity via
      stereocontrolled Pd(0)-Cu(I) cocatalyzed aromatic phosphorylation

PMID- 10959895
TI  - Enantioselective synthesis of unnatural (S)-(+)-cocaine.

PMID- 10959897
TI  - Enzymatic acylation and ring-closing olefin metathesis: a convenient strategy for
      the lactone moiety of compactin and mevinolin.

PMID- 10959898
TI  - Distinguished Career Award of the American Society of Pediatric
      Hematology/Oncology for 2000.

PMID- 10959899
TI  - Therapy-related leukemia: is the risk life-long and can we identify patients at
      greatest risk.

PMID- 10959900
TI  - MGI 114: augmentation of antitumor activity when combined with topotecan.
AB  - PURPOSE: 6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic
      analogue of the mushroom toxin illudin S that has been shown to be a potent
      cytotoxic agent with an improved therapeutic index compared with its parent
      compound. The studies were conducted to evaluate the antitumor activity of MGI
      114 as a single agent and in combination with topotecan against pediatric solid
      tumor cell lines and xenograft models. MATERIALS AND METHODS: In vitro studies
      were designed to determine the cytotoxic potential of MGI 114 using the MTT assay
      and 13 pediatric tumor cell lines. In addition, combination in vitro studies were
      performed with MGI 114 and topotecan to generate isoeffect plots. Single agent
      and combination in vivo studies were also performed using MGI 114 against
      rhabdomyosarcoma and neuroblastoma xenograft models. RESULTS: After a 1-hour
      exposure to MGI 114, the mean IC50 (+/-standard error of mean) for
      medulloblastoma, neuroblastoma, Ewing sarcoma/primitive neuroectodermal tumor,
      and rhabdomyosarcoma cell lines were 1.58+/-0.51, 1.60+/-0.82, 1.18+/-0.08, and
      3.99+/-1.69 microg/mL, respectively. When tumor cells were exposed concurrently
      to MGI 114 and topotecan, evidence of synergy was observed in 10 of 12 (83%) cell
      lines. Single agent and combination in vivo studies with MGI 114 showed that this
      agent had substantial, and at times curative, antitumor activity against
      rhabdomyosarcoma and neuroblastoma xenograft tumors. CONCLUSIONS: These data
      suggest that MGI 114 has significant efficacy as a single agent in preclinical
      studies against pediatric tumors. In addition, based on previous reports and the
      results presented here, combining MGI 114 with topotecan appears to be an
      attractive approach to the treatment of pediatric malignancies. After completion
      of the pediatric phase I studies of MGI 114, consideration should be given to
      phase II single agent and phase I combination studies with a topoisomerase I
      inhibitor such as topotecan or irinotecan.

PMID- 10959901
TI  - Antineuronal antibodies in patients with neuroblastoma and paraneoplastic
      opsoclonus-myoclonus.
AB  - PURPOSE: To identify serologic markers in children with paraneoplastic opsoclonus
      myoclonus (POM). MATERIALS AND METHODS: We examined the sera of 64 children with
      neuroblastoma (16 with POM and 48 age-matched and stage-matched controls) by
      immunohistochemistry of rat brain and human cerebellum, and by Western blot
      analysis of protein extracts from human Purkinje cells, cortical neurons,
      neuroblastoma cell lines, and HuD. RESULTS: Using immunohistochemistry, IgG
      reactivity against neurons was identified in 13 of 16 POM sera (81%), and 12 of
      48 non-POM sera (25%; P<0.001). IgM antineural antibodies were present in 3 of 16
      POM sera (19%) and 11 of 48 (23%) non-POM sera. Except for anti-Hu antibodies
      detected in 10 sera (4 with POM), no other specific reactivities were identified
      by Western blot analysis of neuronal or of neuroblastoma protein extracts.
      CONCLUSIONS: We conclude that: 1) patients with neuroblastoma and POM are more
      likely to harbor antineuronal antibodies than patients without POM; 2) no
      specific serologic marker of POM was identified, but the frequent presence of
      antineuronal antibodies suggests that POM is immune-mediated; and 3) anti-Hu
      antibodies are present in some sera from patients with neuroblastoma,
      irrespective of the presence of POM.

PMID- 10959902
TI  - Hematologic abnormalities and acute myeloid leukemia in children and adolescents
      administered intensified chemotherapy for the Ewing sarcoma family of tumors.
AB  - PURPOSE: Current treatment of the Ewing sarcoma family of tumors (ESFT) includes
      intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating
      agents, and granulocyte colony-stimulating factor (G-CSF). This treatment
      approach has been associated with myelodysplasia and acute myeloid leukemia.
      Because macrocytosis and thrombocytopenia are distinctive features of
      myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to
      determine the degree and duration of macrocytosis and thrombocytopenia and their
      relation with the development of therapy-related hematologic malignancies.
      PATIENTS AND METHODS: The study group consisted of 73 patients with ESFT treated
      on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens
      incorporated the same agents but differed in cumulative drug dose, dose per
      course, and the use of G-CSF. Platelet counts and the mean corpuscular volume
      (MCV) of erythrocytes were determined at diagnosis and during follow-up visits
      after completion of treatment. RESULTS: Patients in the EW92 group had
      significantly greater MCVs after treatment than did the less intensively treated
      EW87 group. These changes persisted throughout the 40-month observation period.
      Patients in the EW92 group also had lesser mean platelet counts after treatment
      than those in the EW87 group. MCV differences (from baseline) were inversely
      related to platelet counts. The cumulative incidence of treatment-related acute
      myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the
      EW87 group. CONCLUSION: Patients treated for ESFT with intensive chemotherapy
      that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF
      characteristically have persistently elevated MCVs and decreased platelet counts
      after completion of therapy. These hematologic abnormalities may represent stem
      cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia,
      but further study is needed to establish this relation.

PMID- 10959903
TI  - Use of hydroxyurea in children ages 2 to 5 years with sickle cell disease.
AB  - The efficacy and side effects of hydroxyurea in young children with sickle cell
      disease are unknown. The authors followed-up eight young children (mean age 3.7
      years) during therapy with hydroxyurea for an average of 137 weeks. Total and
      fetal hemoglobin levels rose with hydroxyurea therapy. Hospital admission rates
      and total hospital days decreased during hydroxyurea therapy. No unexpected
      toxicity occurred, and growth and development were unaffected. This pilot study
      suggests that hydroxyurea is safe and effective in young children with sickle
      cell disease.

PMID- 10959904
TI  - Multicenter comparison of magnetic resonance imaging and transcranial Doppler
      ultrasonography in the evaluation of the central nervous system in children with
      sickle cell disease.
AB  - PURPOSE: To compare the results of standardized magnetic resonance imaging (MRI)
      of the brain and transcranial Doppler (TCD) ultrasonography of cerebral arteries
      in school-aged children with sickle cell disease to determine the correlation
      between these two different neurodiagnostic tests. PATIENTS AND METHODS: Data
      were analyzed from 78 children with sickle cell disease (mean age 11 yrs) who
      participated in both the Cooperative Study of Sickle Cell Disease (CSSCD) and the
      Stroke Prevention Trial in Sickle Cell Anemia (STOP). Patients who had
      experienced an overt stroke were excluded. MRI findings were classified as normal
      or "silent infarct." Results of TCD were classified as normal, conditional, or
      abnormal, based on the time-averaged maximum mean flow velocity in the proximal
      middle cerebral and distal internal carotid arteries. RESULTS: Of 61 patients who
      had a normal MRI examination, 11 (18%) had either conditional (5 patients) or
      abnormal (6 patients) TCD results. Among 17 patients in whom silent infarction
      was seen on MRI, only 5 (29%) had a conditional (1 patient) or abnormal (4
      patients) TCD velocity. Thus, discordant results were seen in 23 patients: 12 in
      which the TCD result was normal and the MRI abnormal; 11 in which the TCD
      velocity was elevated and the MRI normal. CONCLUSIONS: Abnormal TCD and MRI
      examinations reveal different aspects of the pathophysiology of central nervous
      system (CNS) injury in sickle cell disease and are often discordant. Although TCD
      abnormality is predictive of overt stroke, the lack of concordance between TCD
      and MRI findings suggests a need to develop more sensitive and specific
      indicators of early CNS pathology, such as neuropsychometric testing and positron
      emission tomography (PET) scans, and to obtain more information about
      microvascular pathologic processes that may affect CNS function.

PMID- 10959905
TI  - Trimethoprim-sulfamethoxazole salvage for refractory listeriosis during
      maintenance chemotherapy for acute lymphoblastic leukemia.
AB  - A 5-year-old boy with acute lymphoblastic leukemia (ALL) and intolerance to oral
      trimethoprim-sulfamethoxazole (TMP/SMX) had Listeria monocytogenes bacteremia and
      meningitis develop during maintenance chemotherapy. Despite prompt administration
      of IV amoxicillin/gentamicin and microbiologic clearance of the bloodstream, the
      patient had no response to therapy after a course of 7 days. Intravenous TMP/SMX
      (10 mg/kg per day of TMP) was added to the antibiotic regimen after
      desensitization. Fever and meningeal signs rapidly resolved, and the patient was
      ultimately cured. Amoxicillin and gentamicin, although highly active and
      synergistic in vitro against L. monocytogenes, have limited intracellular
      penetration and activity. In contrast, TMP/SMX has bactericidal extracellular and
      intracellular activity against Listeria and excellent central nervous system
      penetration, and thus may be effective for the treatment of refractory
      listeriosis.

PMID- 10959906
TI  - Continuous octreotide infusion for the treatment of secretory diarrhea caused by
      acute intestinal graft-versus-host disease in a child.
AB  - This report describes the use of octreotide, a synthetic somatostatin analogue,
      for severe diarrhea caused by acute intestinal graft-versus-host disease (GVHD)
      after bone marrow transplantation. A 22-month-old boy suffered grade 4 intestinal
      GVHD, with profuse diarrhea, intestinal inflammation, and grossly bloody stools
      after matched, unrelated donor transplant for biphenotypic leukemia. He required
      intensive blood product support. In addition to aggressive anti-GVHD therapy,
      octreotide acetate was initiated at 30 microg (2 microg/kg) intravenously 3 times
      per day and escalated to continuous infusion at 15 microg/hr (1 microg/kg per
      hour). The diarrhea did not improve with anti-GVHD treatment. However, moderate
      dose octreotide therapy resulted in prompt control of the bloody diarrhea, which
      rebounded on cessation of octreotide therapy. Rebound diarrhea responded promptly
      when the dose of octreotide was escalated. Octreotide was associated with an
      exacerbation of preexisting hypertension, but it appeared to be effective for
      control of severe, bloody diarrhea caused by acute GVHD in a child, with
      manageable side effects. Further studies of this application in infants and
      children are warranted.

PMID- 10959907
TI  - Neonatal lupus erythematosus with microvascular hemolysis.
AB  - A female, term newborn born to a mother with a history of idiopathic
      thrombocytopenic purpura and antinuclear antibodies, single-stranded A antibody,
      and IgM anticardiolipin antibodies presented with immune thrombocytopenia,
      disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia,
      and a characteristic lupus rash in the periorbital areas. She responded to
      combined treatment with dexamethasone and intravenous immunoglobulin (IVIG). At
      age 9 months, she was readmitted with severe thrombocytopenia, DIC, and
      microangiopathic hemolytic anemia. She again responded to IVIG. This suggests
      that microangiopathic hemolysis can be a presenting symptom in neonatal lupus
      erythematosus and that reoccurrence of the microangiopathic hemolysis may occur
      even after the disappearance of lupus antibodies.

PMID- 10959908
TI  - Langerhans cell histiocytosis after therapy for a malignant germ cell tumor of
      the central nervous system.
AB  - Langerhans cell histiocytosis (LCH) is a clonal neoplastic disorder that results
      in a spectrum of clinical manifestations. Known to be associated with a variety
      of malignant diseases, LCH may precede, coincide with, or develop after the
      diagnosis of cancer. A child with a malignant germ cell tumor of the brain who
      subsequently experienced LCH is reported. The 8-year-old boy was treated for an
      immature teratoma of the posterior fossa with gross total resection and
      craniospinal irradiation preceding bleomycin, etoposide, and vinblastine
      chemotherapy for four cycles. Seven months after completion of therapy, he
      experienced multifocal bone disease with LCH.

PMID- 10959909
TI  - Spontaneous humerus fracture and osteoporosis: an unusual initial presentation of
      acute lymphoblastic leukemia.

PMID- 10959910
TI  - Acute stroke-like encephalopathy associated with high-dose methotrexate
      impurities.

PMID- 10959911
TI  - Pyoderma gangrenosum in a child with myelodysplastic syndrome.

PMID- 10959912
TI  - Statistical analysis of the long-term effects of recombinant human
      deoxyribonuclease on pulmonary function in cystic fibrosis patients.
AB  - The problem of evaluating the long-term effects of recombinant human
      deoxyribonuclease (rhDNase) on forced expiratory volume in one second (FEV1) in
      cystic fibrosis (CF) patients was considered. A two-stage mixed effects model,
      incorporating relevant predictive variables, captured the diverse patterns of
      decline of FEV1 for patients with different demographic characteristics. Based on
      the results of modeling the dropout process, it is clear that the probability of
      early dropout was closely related to patient's responsiveness to rhDNase
      treatment. Failure to consider the existence of informative censoring severely
      biased the estimates of the rate of decline and affected the interpretation of
      the results.

PMID- 10959913
TI  - Robustness of the quartiles of survival time and survival probability.
AB  - A simulation study was undertaken to investigate the robustness of the quartiles
      of survival times, survival probability (when survival time was equal to the
      quartile), and regression coefficients in the presence of covariates [by
      comparing the estimated values under the correct model (Weibull) with those
      obtained under the assumed models, such as Weibull, exponential, loglogistic, Cox
      proportional hazards, and product-limit estimator] when the assumptions related
      to the underlying model were violated. Two simulation experiments were conducted:
      the first for when the underlying model was Weibull with no covariate, and the
      second for when the underlying model was Weibull with one continuous covariate.
      An evaluation of the objectives of this study was done utilizing a real data set
      from the Lung Cancer Study Group 771. The results for both simulation experiments
      were quite comparable and consistent. In general, the exponential model performed
      poorly in estimating the quartiles (except the median) and the survival
      probabilities. The loglogistic model and product-limit estimator performed
      reasonably well for lower quartile and median. For the upper quartile when the
      shape parameter was less than 1.5 the performance was poor. For the regression
      coefficients, the estimates for beta1 and beta2 were biased under exponential
      model and the estimate for mu was quite biased under the loglogistic model. The
      performance of the Cox model was quite reasonable and only when the shape
      parameter was 0.7, the amount of bias for beta2 was slightly more than 10%. The
      results for the real data and the simulated data were comparable, which
      demonstrates the real application of this study.

PMID- 10959914
TI  - A two-stage dose selection strategy in phase I trials with wide dose ranges.
AB  - At early stages of drug development, the maximum tolerated dose (MTD) must be
      determined in order to have a range of doses that can be safely administered in
      humans. This is necessary before the compound can be tested in phase II clinical
      trials to find the optimal dose in terms of clinical outcome. Although heavily
      criticized, traditional dose escalation methods are still widely used to estimate
      the MTD. The recently developed Continual Reassessment Method (CRM) and Logistic
      Dose Ranging Strategy (LDRS) offer advantages compared to the traditional
      approach, including improved estimation of the MTD. However, the CRM utilizes a
      prior distribution that must be specified before having any data from the current
      trial. The LDRS requires the use of hypothesized data through a seed data set
      established before the start of the trial. When a wide dose range needs to be
      tested, the assumed information (prior distribution or seed data set) can have a
      great impact on dosages used during the trial and on the final estimates of the
      MTD. This paper combines the LDRS and the traditional dose escalation procedure
      to suggest a practical two-stage method that provides reliable estimates through
      relatively easy computation, and yet requires almost no prior information.

PMID- 10959915
TI  - Simultaneous testing strategy for comparing two treatments in a stratified
      binomial trial.
AB  - The Mantel-Haenszel (M-H) procedure is commonly used to compare two treatments in
      a stratified binomial trial. However, this procedure is asymptotically optimal
      only if the odds ratio is constant across strata. We propose an alternative
      analytic strategy based on the simultaneous use of two statistics, ZS and ZI,
      each involving a weighted averaging of within-stratum differences between
      proportions. The two treatments are declared significantly different at overall
      level alpha if either min(ZS, ZI) > Zalpha/2 or max(ZS, ZI) > Zalpha*/2, where
      alpha* is data dependent. Our strategy is shown to be more powerful than the M-H
      and other related procedures. Numerical examples are provided for illustration.

PMID- 10959916
TI  - Optimal designs for the individual and joint exposure general logistic regression
      models.
AB  - Interest in administering compounds in combination lies both in enhancing
      efficacious effects and in limiting adverse effects. Although much statistical
      work has focused on developing mathematical functions to model the joint dose
      response curves, relatively little work exists in regard to designing experiments
      for assessing joint action. A variety of parametric dose-response models based on
      either the normal or logistic probability distribution have been proposed in the
      literature. These models are typically nonlinear in the parameters, and as such,
      a nonlinear weighted least squares approach can be employed for the purpose of
      designing experiments. The approach is applicable across a wide variety of
      settings commonly associated with joint action data, including continuous and
      discrete responses, alternative error structures, and nonzero background
      response. Further, designs can be expressed in terms of proportionate responses
      associated with the individual compounds rather than dose levels, thereby
      providing for results that are applicable across compounds. As a precursor to
      this effort, optimal and minimal experimental designs for the case in which a
      single compound is administered have also been developed. Although the proposed
      methodology for deriving experimental designs can be applied to any nonlinear
      regression model, primary focus is given to the additive and nonadditive
      independent joint action (IJA) models for individual and combined exposures
      proposed by Barton, Braunberg, and Friedman (1).

PMID- 10959917
TI  - Modeling pharmacokinetic data using heavy-tailed multivariate distributions.
AB  - Pharmacokinetic studies of drug and metabolite concentrations in the blood are
      usually conducted as crossover trials, especially in Phases I and II. A
      longitudinal series of measurements is collected on each subject within each
      period. Dependence among such observations, within and between periods, will
      generally be fairly complex, requiring two levels of variance components, for the
      subjects and for the periods within subjects, and an autocorrelation within
      periods as well as a time-varying variance. Until now, the standard way in which
      this has been modeled is using a multivariate normal distribution. Here, we
      introduce procedures for simultaneously handling these various types of
      dependence in a wider class of distributions called the multivariate power
      exponential and Student t families. They can have the heavy tails required for
      handling the extreme observations that may occur in such contexts. We also
      consider various forms of serial dependence among the observations and find that
      they provide more improvement to our models than do the variance components. An
      integrated Ornstein-Uhlenbeck (IOU) stochastic process fits much better to our
      data set than the conventional continuous first-order autoregression, CAR(1). We
      apply these models to a Phase I study of the drug, flosequinan, and its
      metabolite.

PMID- 10959918
TI  - Linear mixed-effect multivariate adaptive regression splines applied to nonlinear
      pharmacokinetics data.
AB  - In a frequently performed pharmacokinetics study, different subjects are given
      different doses of a drug. After each dose is given, drug concentrations are
      observed according to the same sampling design. The goal of the experiment is to
      obtain a representation for the pharmacokinetics of the drug, and to determine if
      drug concentrations observed at different times after a dose are linear in
      respect to dose. The goal of this paper is to obtain a representation for
      concentration as a function of time and dose, which (a) makes no assumptions on
      the underlying pharmacokinetics of the drug; (b) takes into account the repeated
      measure structure of the data; and (c) detects nonlinearities in respect to dose.
      To address (a) we use a multivariate adaptive regression splines representation
      (MARS), which we recast into a linear mixed-effects model, addressing (b). To
      detect nonlinearity we describe a general algorithm that obtains nested (mixed
      effect) MARS representations. In the pharmacokinetics application, the algorithm
      obtains representations containing time, and time and dose, respectively, with
      the property that the bases functions of the first representation are a subset of
      the second. Standard statistical model selection criteria are used to select
      representations linear or nonlinear in respect to dose. The method can be applied
      to a variety of pharmacokinetics (and pharmacodynamic) preclinical and phase I
      III trials. Examples of applications of the methodology to real and simulated
      data are reported.

PMID- 10959919
TI  - On the timing of a futility analysis in clinical trials.
AB  - In recent years, many researchers have been interested in performing futility
      analyses at interim points during clinical trials in order to terminate futile
      trials. To implement such an analysis, the researcher must decide what percentage
      of the total number of patients must have completed the trial before the interim
      analysis is done. This percentage is usually between 20% and 80%. We examined the
      relationship between the percentage chosen and the probability of stopping the
      trial, given a parameter value associated with the treatment effect. The results
      of this examination will help the researcher plan when to do a futility analysis.

PMID- 10959920
TI  - Assessment of selection bias in estimates of relative bioavailability and
      intrasubject variability from bioequivalence evaluations.
AB  - The outcome selection of bioequivalence evaluations for abbreviated new drug
      applications results in bias towards unity of test-reference ratio estimates, and
      underestimation of intrasubject variability for the test drug product. In this
      study, the selection bias in the estimates of testreference ratio and
      intrasubject variability as function of the true testreference ratio,
      intrasubject variability, and sample sizes was derived, and the relationship of
      the selection bias with the true test-reference ratio, intrasubject variability,
      and sample sizes was evaluated using the derived functions for the selection
      bias. It was shown in this study that the selection bias decreases with the true
      test-reference ratio approaching unity, with decreasing intrasubject variability,
      or with increasing sample sizes of bioequivalence trials. As demonstrated in this
      study, the selection bias can reach such high levels that it can result in
      misleading optimism about interchangeability between the bioinequivalent generic
      versions of a reference drug product, especially for highly variable drug
      products. As demonstrated in this study, trial repeating raises the chances for
      test products of low test-reference ratio to meet the bioequivalence
      requirements, and as such inflates value of the expected selec tion bias. The a
      priori knowledge of intrasubject variability for the reference drug product may
      be used to infer the intensity of outcome selection, and as such to predict
      selection bias in test-reference ratio estimates for the test drug product.

PMID- 10959921
TI  - Adjusting dissolution specifications for the variability induced by storage
      conditions.
AB  - The United States Pharmacopeia requires that drug products meet established
      dissolution specifications throughout their shelf life. Whereas chemical
      stability for six months at accelerated storage conditions is generally regarded
      as providing a two-year expiry period, stress conditions are not considered
      predictive of dissolution stability at controlled room temperature. This paper
      presents an application of response surface methodology intended to incorporate
      the variability induced by storage temperature and relative humidity into robust
      product dissolution specifications. Contour plots, depicting one-sided tolerance
      limits of percent released, are presented as a function of crushing strength and
      dissolution time.

PMID- 10959922
TI  - Equivalence in test assay method comparisons for the repeated-measure, matched
      pair design in medical device studies: statistical considerations.
AB  - In medical device clinical studies, including therapeutic device and in vitro
      test assay method studies, the investigator is frequently interested in
      demonstrating the equivalence of clinical response, generally in continuous
      measurements, between a standard assay method and a new assay method over various
      occasions or times. The new assay method may be less invasive or more convenient
      or cheaper to use than the standard assay method. In this paper, several
      statistical approaches are discussed, including various repeated-measure
      regression models, the simultaneous 95% confidence interval for paired mean
      differences derived from Hotelling's multivariate T2 analysis for repeated
      measure, paired data, repeatability and reproducibility studies, and concordance
      correlation coefficient.

PMID- 10959923
TI  - Controversy or hard evidence?

PMID- 10959924
TI  - An alternative slump reduction technique of anterior shoulder dislocations: a 3
      year prospective study.
AB  - OBJECTIVE: To describe an alternative method of dislocated shoulder reduction and
      to investigate its success rate when used at a ski resort setting. DESIGN: A
      prospective observational study. SETTING: Medical center at Australia's largest
      ski resort during the ski seasons of 1994, 1995, and 1996 (June through early
      October). The center is a primary care private practice. PATIENTS: There were 199
      patients with anterior dislocated shoulders who presented to the center. One
      patient was excluded from the study because of spontaneous reduction during
      clothing removal. INTERVENTIONS: Patients had upper body clothing removed, were
      seated in a chair, and supported in a slumped position by an assistant. The
      medical officer then performed the reduction once relaxation was achieved.
      Patients were always offered Entenox (nitrous oxide). MAIN OUTCOME MEASURES:
      Successful reduction of the anterior dislocated shoulder with or without
      analgesia. Any complications such as fractures and nerve damage were recorded.
      RESULTS: The data were recorded by the treating medical officer. 93.2% of the
      subjects were successfully treated using the "slump" reduction method. The
      success rate on first attempt using the slump method was 85.6%. Of the remainder,
      four subjects were reduced by an alternative method and five were sent to
      hospital for reduction under general anesthesia. Four of these subjects had
      fractures. CONCLUSION: The slump method of reduction for anterior dislocated
      shoulders compares favorably with previously documented methods. It would seem to
      be a particularly useful method when parenteral analgesia is either not available
      or relatively contraindicated. There were no complications resulting from the use
      of this method, and it is a method that is easy to learn. The slump method is a
      safe and effective addition to the primary care physician's options in reducing
      an anteriorly dislocated shoulder.

PMID- 10959925
TI  - The association of the menstrual cycle with the laxity of the anterior cruciate
      ligament in adolescent female athletes.
AB  - OBJECTIVE: To identify a significant change in the laxity of the anterior
      cruciate ligament (ACL) in the competitive adolescent female athlete throughout
      the different phases of the menstrual cycle. DESIGN: Prospective, single-blinded
      8-week study set during a winter sports season. SETTING: Suburban Ohio Division I
      high school. PARTICIPANTS: 26 members of gymnastics, soccer, track, tennis, and
      basketball teams. All participants were screened for normal menstrual cycles (26
      30 days, menses 4-7 days long). MAIN OUTCOME MEASURES: KT-1000 arthrometer was
      used to measure laxity by performing repeated measures throughout an 8-week
      period. Measurements were taken before the athletes' workouts. The athlete
      charted the menstrual periods on a monthly calendar. The measurements were then
      grouped into the three phases of the menstrual cycle (follicular, ovulatory, and
      luteal) and averaged. RESULTS: Right knee laxity measured 4.98 mm follicular
      phase, 5.24 mm ovulatory, and 5.09 mm luteal. Left knee laxity measured 4.51 mm
      follicular, 4.43 mm ovulatory, and 4.62 mm luteal. There was no statistical
      difference among the three phases in the left (p = 0.9) and right (p = 0.7977).
      Additionally, left ACL laxity was significantly less in all three phases. We
      found no statistically significant variability in laxity among the five sports
      sampled (p > 0.63 to 0.10) and different ages (p = 0.404). CONCLUSIONS: We found
      an insignificant change in ACL laxity from follicular to luteal phases of the
      menstrual cycle. This indicates that no single phase of the menstrual cycle
      clinically affects the ACL more than the next. Although the presence of sex
      hormones-particularly estrogen-may indeed predispose females to higher ACL injury
      rates, we did not find any evidence that hormonal level changes equate with
      significant ACL laxity changes. We conclude that the menstrual cycle does not
      significantly affect ACL laxity in the competitive adolescent female athlete.

PMID- 10959926
TI  - Hip abductor weakness in distance runners with iliotibial band syndrome.
AB  - OBJECTIVE: To examine hip abductor strength in long-distance runners with
      iliotibial band syndrome (ITBS), comparing their injured-limb strength to their
      nonaffected limb and to the limbs of a control group of healthy long-distance
      runners; and to determine whether correction of strength deficits in the hip
      abductors of the affected runners through a rehabilitation program correlates
      with a successful return to running. DESIGN: Case series. SETTING: Stanford
      University Sports Medicine Clinics. PARTICIPANTS: 24 distance runners with ITBS
      (14 female, 10 male) were randomly selected from patients presenting to our
      Runners' Injury Clinic with history and physical examination findings typical for
      ITBS. The control group of 30 distance runners (14 females, 16 males) were
      randomly selected from the Stanford University Cross-Country and Track teams.
      MAIN OUTCOME MEASURES: Group differences in hip abductor strength, as measured by
      torque generated, were analyzed using separate two-tailed t-tests between the
      injured limb, non-injured limb, and the noninjured limbs of the control group.
      Prerehabilitation hip abductor torque for the injured runners was then compared
      with postrehabilitation torque after a 6-week rehabilitation program. RESULTS:
      Hip abductor torque was measured with the Nicholas Manual Muscle Tester (kg), and
      normalized for differences in height and weight among subjects to units of
      percent body weight times height (%BWh). Average prerehabilitation hip abductor
      torque of the injured females was 7.82%BWh versus 9.82%BWh for their noninjured
      limb and 10.19%BWh for the control group of female runners. Average
      prerehabilitation hip abductor torque of the injured males was 6.86%BWh versus
      8.62%BWh for their noninjured limb and 9.73%BWh for the control group of male
      runners. All prerehabilitation group differences were statistically significant
      at the p < 0.05 level. The injured runners were then enrolled in a 6-week
      standardized rehabilitation protocol with special attention directed to
      strengthening the gluteus medius. After rehabilitation, the females demonstrated
      an average increase in hip abductor torque of 34.9% in the injured limb, and the
      males an average increase of 51.4%. After 6 weeks of rehabilitation, 22 of 24
      athletes were pain free with all exercises and able to return to running, and at
      6-months follow-up there were no reports of recurrence. CONCLUSIONS: Long
      distance runners with ITBS have weaker hip abduction strength in the affected leg
      compared with their unaffected leg and unaffected long-distance runners.
      Additionally, symptom improvement with a successful return to the preinjury
      training program parallels improvement in hip abductor strength.

PMID- 10959927
TI  - Evaluation of outcomes in patients following surgical treatment of chronic
      exertional compartment syndrome in the leg.
AB  - OBJECTIVE: To evaluate outcomes in patients who had a fasciotomy performed on
      their leg(s) for chronic exertional compartment syndrome (CECS). DESIGN: A
      retrospective descriptive cohort study. SETTING: Tertiary care sport medicine
      referral practice. PATIENTS: A consecutive series of 62 patients surgically
      treated for CECS from January 1991 to December 1997. MAIN OUTCOME MEASURES: A
      questionnaire was designed and developed to assess pain (using a 100 mm visual
      analogue scale), level of improvement, level of maximum activity, satisfaction
      level, and the occurrence of reoperations. RESULTS: Fifty patients had
      anterior/lateral compartment involvement, 8 patients had deep posterior
      compartment involvement, and 4 patients had anterior/lateral/deep posterior
      compartment involvement. The demographics of the 39 respondents and 23
      nonrespondents were similar. The mean percent pain relief of respondents was 68%
      (95% CI [confidence interval] = 54% to 82%). There was no relationship between
      percent pain relief and the documented immediate post exercise compartment
      pressures. A clinically significant improvement was reported by 26 of 32 (81%)
      anterior/lateral compartment patients and 3 of 6 (50%) patients with deep
      posterior compartment involvement. Patient level of activity after fasciotomy was
      classified as equal to or higher than before the operation with a lesser degree
      of pain by 28 of 36 (78%) patients, while 8 of 36 (22%) patients reported lower
      activity levels than before the operation. Of the patients reporting lower
      activity, seven were due to exercise related pain in the post operative leg(s)
      and one was due to lifestyle changes. Thirty of 38 patients (79%) were satisfied
      with the outcome of the operation. Four of 62 patients (6%) failed the initial
      surgical procedure and required revision surgery for exercise-induced pain. In
      addition, one of these individuals also had a sympathectomy and another had a
      neurolysis performed at the time of revision surgery. Three of the 62 (5%)
      patients had subsequent operations for exercise-induced pain on different
      compartments than the initial surgical procedure. One individual had an
      unsuccessful operative repair of a posttraumatic neuroma. Postoperative
      complications were reported by 5 of 39 (13%) patients in the additional comments
      section of the questionnaire. CONCLUSIONS: The majority of patients surgically
      treated for CECS experience a high level of pain relief and are satisfied with
      the results of their operation. The level of pain relief experienced by patients
      is not related to the magnitude of the immediate post exercise compartment
      pressures. Despite the possibility that some patients have less favorable
      outcomes, experience complications, or need subsequent operations, fasciotomy is
      recommended for patients with CECS as there is no other treatment for this
      condition.

PMID- 10959928
TI  - Team sports participation and risk-taking behaviors among a biracial middle
      school population.
AB  - OBJECTIVE: There have been no large studies of middle school students to assess
      the association between team sports participation and risk-taking behaviors,
      despite evidence in high school and collegiate athletes. Our study evaluated
      whether team sports participation is associated with specific risk-taking
      behaviors among a biracial middle school population. DESIGN: A cross-sectional
      survey using the Youth Risk Behavior Survey: Middle School Questionnaire.
      SETTING: Twenty-two public middle schools in three rural counties in eastern
      North Carolina. PARTICIPANTS: 4,346 middle school students in grades 6-8
      completed the survey. All students participated if present in school the day the
      survey was administered. 648 students fulfilled specific exclusion criteria. MAIN
      OUTCOME MEASURE: Multiple logistic regression examined team sports participation
      as a predictor of 17 risk-taking behaviors while controlling for gender, race,
      and grade. RESULTS: Of the 3,698 students, 49% were male, 49.5% Caucasian, and
      52.5% were involved in team sports. Sports participants, as compared with non
      sports participants, reported significantly higher frequencies for carrying a gun
      (p < 0.001), carrying a weapon (p < 0.001), being in a physical fight (p <
      0.001), current use of alcohol (p = 0.001), and experimentation with cigarettes
      and chewing tobacco (p < 0.001). In the multiple logistic regression analysis
      team sports participation was associated with the following behaviors: carrying a
      weapon (odds ratio 1.25, 95% confidence intervals 1.0731-1.4540), physical fight
      (1.15, 1.0017-1.3253), current alcohol use (1.24, 1.0560-1.4611), and
      experimentation with cigarettes (1.26, 1.0991-1.4502), cocaine (1.37, 1.0300
      1.8139) and inhalants (1.20, 1.0141-1.4130). CONCLUSIONS: Among a biracial middle
      school population, sports participants were more likely to demonstrate certain
      risk-taking behaviors when compared with non-sports participants. Further
      research is necessary to understand the relationships between risk-taking
      behaviors and team sports participation.

PMID- 10959929
TI  - Creatine supplementation patterns and perceived effects in select division I
      collegiate athletes.
AB  - OBJECTIVE: To describe patterns of creatine use in select Division I collegiate
      athletes based on recommended dosages according to body weight. Further, to
      report the perceived effects noted with creatine supplementation. DESIGN:
      Anonymous open-ended self-report descriptive questionnaire. SETTING: National
      Collegiate Athletic Association Division I institution. PARTICIPANTS: Two-hundred
      and nineteen male and female collegiate athletes representing eight varsity
      sports. MAIN OUTCOME MEASURE(S): An open-ended questionnaire was administered to
      determine patterns of creatine use during the loading and maintenance phases of
      this nutritional supplement. In addition, perceived positive, negative, and no
      effects associated with creatine usage patterns were determined from athlete
      responses on this self-report measure. RESULTS: Considering this select group of
      collegiate athletes, highly variable patterns of creatine supplementation were
      noted for loading/maintenance phases based on recommended dosages/days and body
      weight. Of the 219 athletes surveyed, 90 (41%) reported using creatine, while
      creatine supplementation was more prevalent among men than women. Creatine users
      (80 athletes, 89%) reporting perceived positive effects were primarily at or
      below recommended dosages for the loading phase but above recommended dosages in
      the maintenance phase. Creatine users (34 athletes, 38%) reporting perceived
      negative effects were primarily at or below recommended dosages in the loading
      phase but noticeably above recommended dosages in the maintenance phase.
      Ironically, all creatine users who reported negative side effects also reported
      positive effects. Creatine users (10 athletes, 11%) reporting no effects were
      below recommended loading dosages but above recommended maintenance dosages.
      CONCLUSIONS: The perceived positive effects noted support current research
      (strength/weight gains), while the perceived negative effects
      (cramping/gastrointestinal distress) were consistent with anecdotal reports
      surrounding creatine supplementation. Apparently, collegiate athletes in this
      study are in need of education regarding the proper use of creatine
      supplementation. Additional studies are needed to ascertain creatine
      supplementation patterns of collegiate athletes in various settings.

PMID- 10959930
TI  - The effects of magnesium supplementation on exercise performance.
AB  - OBJECTIVES: Magnesium (Mg) status, although difficult to assess, is suspected to
      be marginal in many individuals, especially athletes, and this has led to the
      common use of Mg supplements. The purpose of this article is to critique research
      that has addressed Mg supplementation in athletes. DATA SOURCES: The primary
      database was Medline, which was searched for English articles from 1966 to June
      1999 using the words "magnesium" and "supplementation." STUDY SELECTION: Only
      experimental studies dealing with human subjects, Mg supplementation, and
      exercise performance were critiqued (n = 12). DATA EXTRACTION: Quality of
      critiqued articles was based on 1) use of cross-over designs, 2) how and if Mg
      status was assessed, 3) whether treatment was solely Mg supplementation, 4)
      duration of supplementation, 5) subject number, and 6) degree of experimental
      control. Articles were classified into "no effect" and "positive effect," and
      also were examined in regard to the type of performance outcome (strength,
      anaerobic-lactacid, and aerobic). DATA SYNTHESIS: Mg is a cofactor to over 325
      enzymatic reactions, and a deficiency of the mineral therefore has many
      physiological and exercise performance implications. Low dietary intakes, as
      found in many female athletes, coupled with increased urinary losses with
      exercise, may eventually lead to an Mg deficiency. Strength of evidence favors
      those studies finding no effect of Mg supplementation, regardless of whether the
      performance outcome was strength, anaerobic-lactacid, or aerobic. Analysis was
      confounded due to: 1) variable exercise modes, intensities, and durations, 2)
      variable training states and ages of subjects, 3) subject selection favoring
      males and gender differences has not been probed, 4) Mg dosage has ranged from 1
      day to 3 months and from 116 mg/day to 500 mg/day, 5) multivitamins/minerals have
      been ingested with the Mg, 6) with one exception, Mg status was either not
      reported or reliant on total Mg (TMg), 7) lack of a cross-over design, 8) only
      one study made note of controlling exercise prior to exercise testing and blood
      assay, and 9) typical Mg intake measured was only measured in three of the
      studies. CONCLUSIONS: Most evidence indicates no effect of Mg supplementation on
      performance (strength, anaerobic-lactacid, and aerobic). When only peak treadmill
      speed during a VO2 max test is examined, the strength of evidence is equivocal.
      Trained subjects appear to benefit less than untrained subjects, but this
      observation requires further study. Little research has focused on physically
      active females who may be at the highest risk for Mg deficiency. Research has
      been confounded by numerous factors.

PMID- 10959931
TI  - Coarctation of the abdominal aorta as a presentation of the fatigued athlete.

PMID- 10959932
TI  - Baseball: spectator or contact sport?

PMID- 10959933
TI  - Salivary immunoglobulin monitoring in an elite kayaker.

PMID- 10959934
TI  - Guidelines for assessment and management of sport-related concussion. Canadian
      Academy of Sport Medicine Concussion Committee.

PMID- 10959935
TI  - Use of facial protection in ice hockey. Canadian Academy of Sport Medicine Sport
      Safety Committee.

PMID- 10959936
TI  - Does stretching before exercise prevent lower-limb injury?

PMID- 10959937
TI  - Comparison between the GHQ-28 and SF-36 (MH 1-5) for the assessment of the mental
      health in patients with ischaemic heart disease.
AB  - OBJECTIVE: To assess the mental health of patients admitted to hospital with
      suspected ischaemic heart disease, by means of two instruments, the General
      Health Questionnaire (GHQ-28) and the MH (1-5) dimension of the SF-36 Health
      Survey Questionnaire, and to compare the psychometric properties of both
      questionnaires in this population. METHODS: A study was conducted of 185 patients
      consecutively admitted to hospital with suspected ischaemic heart disease,
      classified into four groups: Acute Myocardial Infarctus (AMI), unstable angina,
      non-ischaemic cardiologies, and non-cardiological conditions. Their mental health
      was assessed by means of the GHQ-28 and the MH 1-5 sub-scales of the SF-36; the
      validity of the results were analysed by the association of each instrument with
      socio-demographic (age, sex, social class, and educational level) and clinical
      (co-morbidity, risk factors, diagnostic groups and background to the illness)
      variables. The correlation of each instrument with other sub-scales of the SF-36
      was studied. The internal consistency was measured by Cronbach's alpha, together
      with the item-internal consistency and item-discriminant validity. RESULTS: Of
      the population studied, 71.9% were males and the mean age was 60.2 years (SD:
      10.4). The diagnosis for 33.5% was AMI and for 37.8% unstable angina. For all the
      variables studied, the scores in the two instruments were ordered in the same
      way, and were significantly worse for females and for the most disadvantaged
      social class. None of the scales discriminated in respect of the diagnostic group
      or the presence of comorbidity. However, a linear relationship was observed with
      risk factors. Cronbach's alpha was 0.95 for the GHQ-28 and 0.80 for the MH 1-5.
      Correlations with the other dimensions showed ranges of -0.35 to -0.61 for the
      GHQ-28 and of 0.26 to 0.61 for the MH 1-5. These were highest for the Vitality
      and Social Functioning sub-scales in both instruments. CONCLUSIONS: The
      subjective perception of mental health is measured in a similar way by both the
      MH 1-5 scale of the SF-36 and the GHQ-28. However, since the MH 1-5 questionnaire
      is shorter, it should be administratively easier to introduce into routine
      cardiological practice.

PMID- 10959938
TI  - The North-East-South gradient of coronary heart disease mortality and case
      fatality rates in France is consistent with a similar gradient in risk factor
      clusters.
AB  - In France, the mortality and case fatality rates of coronary heart disease follow
      a decreasing North-East-South gradient. The aim of the study was to evaluate the
      contribution of major cardiovascular risk factors to this gradient. To this end,
      the results of the third population survey of the WHO-MONICA Project conducted in
      three French geographically contrasted regions (the Urban Community of Lille in
      the North, the district of Bas-Rhin in the East and the district of Haute-Garonne
      in the South) are presented. One thousand seven hundred seventy-eight men and
      1730 women aged 35-64 years were randomly selected from the electoral rolls.
      Major coronary heart disease risk factors (hypertension, hypercholesterolemia,
      low high-density lipoprotein (HDL)-cholesterol, obesity, smoking, physical
      inactivity, diabetes) were studied. The results show that the distribution of
      major coronary heart disease risk factors is heterogeneous among geographical
      areas in France. However, the proportion of subjects with more than three risk
      factors is higher in the North than in the other regions and the number of
      subjects with no risk factor is higher in the South than in the other areas. This
      distribution of risk factors among regions supports the hypothesis that
      accumulation of coronary heart disease risk factors contributes to the decreasing
      North-East-South gradient of cardiovascular mortality rates in France.

PMID- 10959939
TI  - A population-based case-control teratologic study of oral chloramphenicol
      treatment during pregnancy.
AB  - The objective of the study was to check the human teratogenic potential of oral
      chloramphenicol treatments during pregnancy. Pair analysis of cases with
      congenital abnormalities and matched population controls was performed in the
      large population-based dataset of the Hungarian Case Control Surveillance of
      Congenital Abnormalities, 1980-1996. Of 38,151 pregnant women who had babies
      without any defects (control group), 51 (0.13%), while of 22,865 pregnant women
      who had newborn infants or fetuses with congenital abnormalities, 52 (0.23%)
      pregnant women were treated with oral chloramphenicol. The case-control pair
      analysis did not show any human teratogenic potential of chloramphenicol during
      the second-third months of pregnancy in the different groups of congenital
      abnormalities. The occurrence of chloramphenicol treatment in the total control
      group as referent was compared with the occurrence of chloramphenicol treatment
      in the different congenital abnormality groups during the second-third months of
      gestation (i.e., in the critical period for major congenital abnormalities) and a
      higher adjusted OR for this drug was found only in the group with undescended
      testis based on only two cases. At the evaluation of medically documented
      chloramphenicol treatment a higher OR was not found in any congenital
      abnormalities. Thus, chloramphenicol treatment during early pregnancy presents
      little, if any, teratogenic risk to the fetus in humans.

PMID- 10959940
TI  - Additional information from parental questionnaires and pharmacy records for
      registration of birth defects. EuroMAP-group.
AB  - EUROCAT Northern Netherlands registers children born with a birth defect in the
      Northern Netherlands. Data used to be collected via a notification form, which is
      filled out by the notifier and, if necessary, completed by the general
      practitioner. To increase the amount of information, EUROCAT started using new
      methodology in July 1997. The new procedure consists of three additional steps.
      Firstly, a parental questionnaire with 43 questions concerning pregnancy and
      medical history is sent to the parents. Also, the pharmacist is approached to
      provide information on the drugs that were dispensed to the mother in the period
      from three months before until the end of the pregnancy. The last step is a
      telephone interview with the mother. In this study the old and new method are
      compared with respect to response, quality and quantity of the data. Of the 198
      parental questionnaires included in this study, 179 (90.4%) were returned. The
      pharmacists returned 173 out of 179 requests for information (96.6%). The
      parental information is more complete for ethnicity and serum screening. The
      quality of the drug exposure data is much better using the new methodology. The
      general practitioner's input is still necessary for specification and
      verification of the diagnosis.

PMID- 10959941
TI  - Path analysis on the risk of mortality in very low birth weight infants.
AB  - OBJECTIVE: The purpose of this work is to clarify by path analysis which of the
      predictor factors of mortality in a cohort of 423 singletons VLBW infants born at
      Beilinson Medical Center during the years 1980-1990 (pre-surfactant era) exert
      direct or indirect effect on mortality. A direct risk factor was defined as a
      factor having an immediate effect on the outcome without working through an
      intermediate variable. By contrast, an indirect risk factor was defined as a
      factor that does not have a direct effect on the risk of mortality but instead
      works through an intermediate variable. Evaluation of mortality was done at three
      points over time (pre-delivery, at birth and post-delivery). RESULTS: In the pre
      delivery model, gestational age, appropriateness for gestational age, mother's
      age and fetal distress work directly on mortality in VLBW infants. At birth,
      mother's age, birth weight and Apgar score at the fifth minute work directly on
      the risk of mortality. When the assessment of the risk of death was done post
      delivery, mother's age, birth weight, Apgar score at the fifth minute and
      seizures influence directly on mortality risk, and fetal distress, gestational
      age and pre-natal induced hypertension (PIH) operate indirectly on the risk of
      mortality. CONCLUSION: The methodology we have used can be adopted in other
      investigations to distinguish and measure the effect of prognostic factors on the
      risk of an outcome.

PMID- 10959942
TI  - Spina bifida and parental occupation: results from three malformation monitoring
      programs in Europe.
AB  - As the evidence for an association between spina bifida and parental agricultural
      occupations is inconclusive, we evaluated this association and the potential
      associations between spina bifida and other parental occupations. Three register
      based case-referent studies were conducted in Sweden, Spain, and Hungary. From
      the registries of congenital malformations in each country, 482, 478, and 1119
      cases with spina bifida were identified, respectively. Identified as referents
      were 964, 434, and 1489 children without abnormalities. Information on parental
      occupation was available in the registries from questionnaires or interviews
      conducted among the parents. Occupations with a potential for physical or
      chemical exposure were compared to non-exposed occupations. Increased odds ratios
      (ORs) were observed for women in agricultural occupations in Sweden (OR: 1.8, 95%
      CI: 0.8-4.2) and in Spain (OR: 2.2, 95% CI: 0.8-5.9), but not in Hungary (OR:
      1.1, 95% CI: 0.7-1.7). Several other parental occupations were analysed, but the
      associations with spina bifida were inconsistent. Concluding, the results are not
      totally consistent but point to an increased risk of spina bifida among women in
      agricultural occupations.

PMID- 10959943
TI  - Creutzfeldt-Jakob disease in health professionals in Slovakia.
AB  - Creutzfeldt-Jakob disease (CJD) is the most important human transmissible
      spongiform encephalopathy (prion disease), recognised in sporadic, genetic but
      also iatrogenic forms. The identification of 8 health care workers in a group of
      114 definitive CJD patients in Slovakia suggested the possibility of
      professionally acquired CJD and induced the investigation of potential endo- and
      exogenous risk factors. In CJD-affected health professionals special attention
      was paid to a detailed occupational history, including a possible professional
      contact with CJD patient and to the findings characteristic for iatrogenic CJD:
      early cerebellar symptomatology, long duration of the disease, absence of typical
      EEG finding and homozygosity of PRNP gene at codon 129. Analysis of
      epidemiological, clinical and molecular biological data in investigated group of
      CJD-affected health professionals gave no evidence of an occupational risk for
      CJD.

PMID- 10959944
TI  - Intake of flavonoids and risk of dementia.
AB  - It has been postulated that oxidative stress may play a key role in dementia.
      This is substantiated by the recent discovery of the protective effect of wine.
      In wine, the flavonoids--powerful antioxidant substances also contained in tea,
      fruits and vegetables--have been thought to offer such protection. We
      investigated whether flavonoid intake could be associated with a lower incidence
      of dementia in a cohort of 1367 subjects above 65 years of age (Paquid). A
      questionnaire was used to evaluate their intake of flavonoids and subjects were
      followed-up for 5 years between 1991 and 1996: 66 incident cases of dementia were
      observed. We estimated the relative risk (RR) of dementia according to tertiles
      of flavonoid intake using a Cox model. The age-adjusted RR of dementia was 0.55
      for the two highest tertiles compared to the lowest (95% CI: 0.34-0.90; p =
      0.02). After additional adjustment for gender, education, weight and vitamin C
      intake, the RR was 0.49 (95% CI: 0.26-0.92; p = 0.04). We conclude that the
      intake of antioxidant flavonoids is inversely related to the risk of incident
      dementia.

PMID- 10959945
TI  - Migration bias in ecologic studies.
AB  - Differential migration may provoke bias in an epidemiological assessment of the
      public health risks from exposure to environmental agents, particularly in
      ecologic studies of health outcomes with a long latency or induction period. The
      potential impact of migration bias on epidemiological research is complex, and it
      depends not only on the direction of the factor-related migration, but also on
      its extent. This study shows that even a small amount of differential migration
      can bias the assessment of the exposure outcome relationship. Migration bias may
      result from a number of circumstances that are related to the way in which
      'populations' are defined and ascertained. It is important to understand and
      minimise this type of bias in epidemiological research.

PMID- 10959946
TI  - Effects of perceived job stress on mental health. A longitudinal survey in a
      Japanese electronics company.
AB  - We conducted a cohort study for 2 years to examine the causal relationship
      between perceived job stress and mental health. Questionnaire surveys, including
      a 30-item General Health Questionnaire (GHQ) and a questionnaire on perceived job
      stress were carried out every 6 months for 2 years. To clarify the causal
      relationship between job stress and mental health, we followed a group of workers
      who initially had a GHQ score < or = 7. Out of 462 workers who were thought to be
      in a healthy mental state, 282 were successfully followed for 2 years. We
      considered subjects who developed unhealthy mental health states (GHQ score > or
      = 8) as hazardous cases. To control potential confounding factors, proportional
      hazard analysis was done. The overall proportion hazardous cases detected in the
      development of an unhealthy mental health state over two years was 55.7%. Using
      Cox's proportional hazard model, workers who complained of perceived job stress
      had a greater hazard than those without job stress. In particular, the item 'poor
      relationship with superior' showed the largest adjusted hazard ratio [95%
      confidence interval (CI)] of 1.51 (1.06-2.15). The item 'too much trouble at
      work' also had a significant hazardous effect on mental health with an adjusted
      hazard ratio (95% CI) of 1.43 (1.00-2.04). Some specific items of perceived job
      stress could cause mental ill health in workers.

PMID- 10959947
TI  - Results of the three-year surveillance by the Italian SALM-NET System: human
      isolates of Salmonella serotypes.
AB  - Within the wide framework of the European Community Human Salmonella Surveillance
      Project (SALM-NET), the data on the most commonly isolated serotypes in Italy
      from January 1994 to December 1996 are reported. The total data included in the
      Italian SALM-NET data base account for 34,412 Salmonella isolates. In the list of
      the most frequent isolates, S. enteritidis ranked always first in the years 1994,
      1995 and 1996 with 5435 (43.4%), 4589 (37.1%) and 4044 (42.4%), respectively,
      over the total number of Salmonella isolates. This serotype is followed by S.
      typhimurium in the list of the top ten isolates, with 2236 (17.9%), 2831 (22.9%)
      and 2239 (23.5%). The other serotypes included in this list accounted for a much
      lower number and percentages ranging from 505 isolates of S. derby (4.0%) to 99
      isolates of S. brandenburg (0.8%).

PMID- 10959948
TI  - Serological evidence of Cryptosporidium infections in southern Europe.
AB  - Although cryptosporidiosis outbreaks have been frequently reported in the United
      States, Canada and the United Kingdom, few outbreaks have been reported on the
      European continent. The reasons for this are unclear. To ascertain whether a
      European population has been previously exposed to Cryptosporidium, we conducted
      a survey of 100 resident blood donors in a northern Italian city for IgG
      serological response to two oocyst antigen groups. A serological response to the
      15/17-kDa antigen group was detected in 83% of blood donors and response to the
      27-kDa antigen group in 62%. Donors who traveled outside of Italy during the
      prior 12 months were less likely to have had a response to the 15/17-kDa antigen
      group (p < 0.04) and to have a less intense response (p < 0.05). Older age was
      predictive of a more intense response to each antigen group (p < 0.01). The
      fraction of Italian blood donors with a serological response to either antigen
      group was higher than in four United States blood donor populations, with
      differences more pronounced for response to the 15/17-kDa antigen group (p <
      0.01). A lower fraction of Italian donors had a serological response to either
      antigen group than persons tested at the time of a cryptosporidiosis outbreak in
      the United States or blood donors tested six months after that outbreak (p <
      0.05). Since the presence of serological responses to these antigen groups
      predicts a reduced risk of cryptosporidiosis, the high prevalence of serological
      responses in these Italian blood donors may explain the infrequent occurrences of
      clinically detectable cryptosporidiosis in this city.

PMID- 10959949
TI  - Reproductive male-mediated risk: spontaneous abortion among wives of pesticide
      applicators.
AB  - This study was conducted among 32 pesticide applicators occupationally exposed to
      pesticides to determine whether paternal exposure is associated with an increased
      risk of spontaneous abortion. The ratio of abortion was compared between
      applicators and a group of 51 food retailers (control population). The ratio of
      abortions/pregnancies for applicators was 0.27 and for retailers 0.07. OR for
      spontaneous abortion adjusted for age of wife and smoking of parents is 3.8 times
      greater than for the control population in the multiple logistic regression model
      and 7.6 times with interaction effects model.

PMID- 10959951
TI  - Atomic force microscope: a tool for studying ionophores
AB  - The aim of the investigations was to show the analytical use of an atomic force
      microscopy (AFM) tip coated with an ion-selective membrane and to show that the
      ion-selective boundary potential is detectable as a force induced by ion
      selective electrostatic interactions, which are more pronounced than double-layer
      forces. This new technique allows the area-specific ion exchange over boundaries
      to be displayed with a destruction-free technique by AFM in an aqueous buffer.
      From experiments with ISEs (ion-selective electrodes), a boundary potential for
      valinomycin was assumed to be established in close vicinity to a K+-releasing
      surface. To trace this boundary potential, an AFM tip was coated with a potassium
      selective polymer film containing valinomycin as used in preparing ISEs. The K+
      releasing substrate was prepared by incorporating a lipophilic potassium salt
      into a plasticized PVC layer. In contact with an electrolyte such as sodium
      chloride solution, an ion exchange takes place. Analogue experiments were
      performed using a sodium-selective ionophore, DD16C5, incorporated into the
      coating of the AFM tip, with a Na+-releasing substrate. The boundary potential
      was traced and investigated with the help of force vs distance curves. The
      resulting adhesion forces for a valinomycin-coated tip in a 150 mM NaCl solution
      were 9.8+/-3.275 nN using a blank PVC substrate and 330.15+/-113.0 nN using a
      substrate containing 10 wt % potassium tetrakis(4-chlorophenyl) borate. The
      selectivity of the ion-selective AFM tips was measured on sodium relative to
      potassium-releasing substrates and studied in different salt solutions with
      concentrations between 10 mmol L(-1) and 1 mol L(-1). For valinomycin, a force
      selectivity coefficient log Kf(K,Na) of -2.5+/-0.5 for K+ against Na+ and a
      selectivity coefficient log Kf(Na,K) of -4 +/- -0.5 for DD16C5 were measured. In
      addition, the surface of the polymer substrate was imaged by AFM in contact mode
      with and without lipophilic potassium salt. The modulation of the force-distance
      curves induced by the ion exchange was compared to the experimental change in
      elasticity of the blank and ion-exchanging substrate. The Young's moduli measured
      with strain force analysis on a potassium-containing substrate were 5 times
      smaller than the ones registered with nanoindentation and did not explain the
      modulation of the force vs distance curves.

PMID- 10959950
TI  - Accurate mass liquid chromatography/mass spectrometry on orthogonal acceleration
      time-of-flight mass analyzers using switching between separate sample and
      reference sprays. 1. Proof of concept.
AB  - This paper describes the use of two separate electrosprays for introducing sample
      and reference for accurate mass liquid chromatography/mass spectrometry (LC/MS)
      on an orthogonal acceleration time-of-flight mass analyzer. This is carried out
      using an adaptation of the multiplexed electrospray ion source in which only two
      of the sprays are utilized. Results are shown for the positive ion detection of
      trace-level components in complex matrixes and good mass accuracies are obtained,
      even for very low level components. An example of accurate mass measurements
      obtained using negative ion LC/MS is also shown. To obtain additional structural
      information, an example of cone voltage fragmentation is included and shows that
      good mass accuracy can be obtained for both precursor and fragment ions.

PMID- 10959952
TI  - Conferring selectivity to chemical sensors via polymer side-chain selection:
      thermodynamics of vapor sorption by a set of polysiloxanes on thickness-shear
      mode resonators
AB  - Entropy of mixing is shown to be the driving interaction for the endothermic
      physisorption process of organic vapor partitioning into seven systematically
      side-chain-modified (polar, acidic, basic, polarizable side groups and groups
      interacting via H-bridges) polysiloxanes on thickness-shear mode resonators. Each
      sensor was exposed to seven analytes, selected for their diversity of functional
      groups. This systematic investigation of sorption yields benchmarking data on
      physisorption selectivity: response data and modeling reveal a direct correlation
      of partition coefficients with interactions between specific polymer side chains
      and analyte functional groups. Partition coefficients were determined for every
      polymer/analyte pairing over the 273-343 K range at 10 K intervals; from
      partition coefficient temperature dependence, overall absorption enthalpies and
      entropies were calculated. By subtracting the enthalpy and entropy of
      condensation for a given pure analyte, its mixing entropy (primarily
      combinatorial) and mixing enthalpy (associated with intermolecular interactions)
      with each polymer matrix were determined. These two crucial thermodynamic
      parameters determine the chemical selectivity patterns of the polymers for the
      analytes. Simple molecular modeling based on the polymer contact surface share of
      the modified side group or the introduced functional group reveals a direct
      correlation between the partition coefficients and the side-group variation.

PMID- 10959953
TI  - Monoclonal antibody--gold biosensor chips for detection of depurinating
      carcinogen--DNA adducts by fluorescence line-narrowing spectroscopy.
AB  - A new direct readout methodology for detection and quantitation of fluorescent
      carcinogen-DNA adducts is described. It combines the binding specificity of an
      immobilized monoclonal antibody (MAb) with high-resolution, low-temperature
      fluorescence spectroscopy. The MAb, which is covalently bound to a gold surface
      via a chemisorbed disulfide coupling agent, binds the adduct of interest in an
      aqueous sample. Laser-induced fluorescence under nonline narrowing (FNLN) and
      line-narrowing (FLN) conditions was used to detect (benzo[a]pyren-6-yl)guanine
      (BP-6-N7Gua) bound to immobilized MAb. At room temperature, the BP-6-N7Gua
      fluorescence was not detected, most likely because of quenching by the gold
      surface and/or efficient dynamical quenching. However, fluorescence was observed
      at room temperature when the surface was covered with a thin layer of glycerol,
      and possible reasons for the fluorescence enhancement are considered. Lowering of
      the temperature to 77 K led to nearly an order of magnitude increase in
      fluorescence intensity. Highly structured FLN spectra obtained at 4.2 K allowed
      for definitive adduct identification. The potential of this methodology for risk
      assessments of individuals exposed to polycyclic aromatic hydrocarbons is
      discussed.

PMID- 10959954
TI  - Probes for detection of specific DNA sequences at the single-molecule level.
AB  - A method has been developed for highly sensitive detection of specific DNA
      sequences in a homogeneous assay using labeled oligonucleotide molecules in
      combination with single-molecule photon burst counting and identification. The
      fluorescently labeled oligonucleotides are called smart probes because they
      report the presence of complementary target sequences by a strong increase in
      fluorescence intensity. The smart probes consist of a fluorescent dye attached at
      the terminus of a hairpin oligonucleotide. The presented technique takes
      advantage of the fact that the used oxazine dye JA242 is efficiently quenched by
      complementary guanosine residues. Upon specific hybridization to the target DNA,
      the smart probe undergoes a conformational change that forces the fluorescent dye
      and the guanosine residues apart, thereby increasing the fluorescence intensity
      about six fold in ensemble measurements. To increase the detection sensitivity
      below the nanomolar range, a confocal fluorescence microscope was used to observe
      the fluorescence bursts from individual smart probes in the presence and absence
      of target DNA as they passed through the focused laser beam. Smart probes were
      excited by a pulsed diode laser emitting at 635 nm with a repetition rate of 64
      MHz. Each fluorescence burst was identified by three independent parameters: (a)
      the burst size, (b) the burst duration, and (c) the fluorescence lifetime.
      Through the use of this multiparameter analysis, higher discrimination accuracies
      between smart probes and hybridized probe-target duplexes were achieved. The
      presented multiparameter detection technique permits the identification of
      picomolar target DNA concentrations in a homogeneous assay, i.e., the detection
      of specific DNA sequences in a 200-fold excess of labeled probe molecules.

PMID- 10959955
TI  - Lateral diffusion of 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine
      perchlorate at the interfaces of C18 and chromatographic solvents
AB  - The influence of mobile phase on the lateral diffusion of an amphiphilic dye was
      studied for four chromatographic interfaces using fluorescence correlation
      spectroscopy. The fluorescent dye was DiI (1,1'-dioctadecyl-3,3,3'3'
      tetramethylindocarbocyanine perchlorate); the stationary phase was a covalently
      bonded monolayer of dimethyloctadecylsiloxane on fused silica; and the four
      mobile phases were acetonitrile, methanol, tetrahydrofuran, and water. Time
      resolved measurements at varying focal positions of the microscope confirmed
      negligible fluorescence from solution. Single-molecule spectroscopy showed that
      exchange between mobile and immobile adsorbates was negligible. The lateral
      diffusion of DiI was the fastest for tetrahydrofuran, D = 5.3 x 10(-5) cm2/s, and
      slowest for water, D = 2.5 x 10(-6) cm2/s. Methanol and acetonitrile gave
      intermediate rates of diffusion, D = 3.4 x 10(-6) and 4.8 x 10(-6), respectively.
      There was no correlation of the lateral diffusion coefficient with solvent
      viscosity, a weak correlation with interfacial tension, and a strong correlation
      with 13C NMR line shapes for the terminal methyl group of the hydrocarbon chain.
      The increased wetting of the C18 interphase in the order water < methanol <
      acetonitrile < tetrahydrofuran agreed with data for the miscibility of these
      solvents with n-hexadecane. It is concluded that the wetting of the hydrocarbon
      interphase by the mobile phase enhances the lateral diffusion of the amphiphile.

PMID- 10959956
TI  - Accurate quantification of H, Li, Be, B, F, Ba, REE, Y, Th, and U in complex
      matrixes: a combined approach based on SIMS and single-crystal structure
      refinement
AB  - A procedure was developed for accurate quantification of REE, actinides, and
      light elements in complex matrixes of interest in earth and material sciences
      (hellandite and britholite, the REE analogue of apatite). These minerals show a
      peculiar chemical composition due to the coexistence of high amounts of LREE, U,
      Th with variable quantities of H, Li, Be, B, and F. Molecular interferences were
      resolved, and problems arising from unpredictable matrix effects and lack of
      reference materials were overcome. X-ray single-crystal structure refinement
      (SREF), which is not affected by matrix effects and does not require analytical
      standardization, was used to precisely estimate (by means of both site-scattering
      value and site geometry) in a wholly independent way the amounts and the
      distribution of the various groups of elements. The combined SIMS-SREF approach
      allowed us to obtain results of impact for mineralogy and also allowed the
      accuracy of SIMS investigation to be fixed. The capabilities of SIMS in the
      quantification of light (Z <6) and heavy (Z >57) elements as both minor and major
      constituents (sigmaREE(ox) up to approximately 70 wt % in britholite) are shown.
      This approach may open new perspectives for the in situ analysis of chemically
      complex materials.

PMID- 10959957
TI  - Testing the significance of microorganism identification by mass spectrometry and
      proteome database search.
AB  - We derive and validate a simple statistical model that predicts the distribution
      of false matches between peaks in matrix-assisted laser desorption/ionization
      mass spectrometry data and proteins in proteome databases. The model allows us to
      calculate the significance of previously reported microorganism identification
      results. In particular, for deltam = +/-1.5 Da, we find that the computed
      significance levels are sufficient to demonstrate the ability to identify
      microorganisms, provided the number of candidate microorganisms is limited to
      roughly three Escherichia coli-like or roughly 10 Bacillus subtilis-like
      microorganisms (in the sense of having roughly the same number of proteins per
      unit-mass interval). We conclude that, given the cluttered and incomplete nature
      of the data, it is likely that neither simple ranking nor simple hypothesis
      testing will be sufficient for truly robust microorganism identification over a
      large number of candidate microorganisms.

PMID- 10959958
TI  - Generation of natural pH gradients in microfluidic channels for use in
      isoelectric focusing
AB  - As a part of an ongoing investigation of the use of isoelectric focusing (IEF) in
      microfluidic devices, pH gradients were electrochemically formed and optically
      quantified in microfluidic channels using acid-base indicators. The microchannels
      consisted of two parallel 40-mm-long electrodes with an interelectrode gap of
      2.54 mm; top and bottom transparent windows were separated by 0.2 mm. Gradients
      in pH were formed as a result of the electrochemical decomposition of water at an
      applied potential not higher than 2.5 V to avoid generation of gas bubbles.
      Solutions contained low concentrations of a single buffer. The stability of the
      pH gradients and their sensitivity to changes in initial conditions were
      investigated under static (nonflow) conditions. Isoelectric focusing of sample
      biological analytes, bovine hemoglobin and bovine serum albumin, was performed to
      illustrate the potential of "microfluidic transverse IEF" for use in continuous
      concentration and separation systems.

PMID- 10959959
TI  - Stripping analysis of nucleic acids at a heated carbon paste electrode.
AB  - A new electrically heated carbon paste electrode has been developed for
      performing adsorptive stripping measurements of trace nucleic acids. Such
      coupling of electrochemistry at electrically heated electrodes with adsorptive
      constant-current stripping chronopotentiometry offers distinct advantages for
      trace measurements of nucleic acids. The application of increased temperatures
      during the deposition step results in dramatic (4-34-fold, depending on
      temperature applied) enhancement of the stripping signal. Such improvement is
      attributed to the accumulation step at the heated electrode. Forced thermal
      convection near the electrode surface facilitates the use of quiescent solutions
      and hence of ultrasmall volumes. Using an electrode temperature of 32 degrees C
      and a quiescent solution during the 1-min accumulation, the response is linear
      over the 1-8 mg/L range tested, with a detection limit of 0.5 mg/L. Such
      electrode heating technology offers great promise for various applications
      involving thermal manipulations of nucleic acids.

PMID- 10959961
TI  - Modification of indium tin oxide electrodes with nucleic acids: detection of
      attomole quantities of immobilized DNA by electrocatalysis
AB  - Indium tin oxide electrodes were modified with DNA, and the guanines in the
      immobilized nucleic acid were used as a substrate for electrocatalytic oxidation
      by Ru(bpy)3(3+) (bpy = 2,2'-bipyridine). Nucleic acids were deposited onto 12.6
      mm2 electrodes from 9:1 DMF/water mixtures buffered with sodium acetate. The DNA
      appeared to denature in the presence of DMF, leading to adsorption of single
      stranded DNA. The nucleic acid was not removed by vigorous washing or heating the
      electrodes in water, although incubation in phosphate buffer overnight liberated
      the adsorbed biomolecule. Acquisition of cyclic voltammograms or
      chronoamperomograms of Ru(bpy)3(2+) at the modified electrodes produced catalytic
      signals indicative of oxidation of the immobilized guanine by Ru(III). The
      electrocatalytic current was a linear function of the extent of modification with
      a slope of 0.5 microA/pmol of adsorbed guanine; integration of the current-time
      traces gave 2.2+/-0.4 electrons/guanine molecule. Use of long DNA strands
      therefore gave steep responses in terms of the quantity of adsorbed DNA strand.
      For example, electrodes modified with a 1497-bp PCR product from the HER-2 gene
      produced detectable catalytic currents when as little as 550 amol of strand was
      adsorbed, giving a sensitivity of 44 amol/mm2.

PMID- 10959960
TI  - In situ assembled mass-transport controlling micromembranes and their application
      in implanted amperometric glucose sensors.
AB  - Micromembranes were assembled by sequentially chemisorbing polyanions and
      polycations on miniature (5 x 10(-4) cm2) enzyme electrodes. The sequential
      chemisorption process allowed the simultaneous tailoring of their sensitivity,
      dynamic range, drift, and selectivity. When assembled on tips of 250-microm
      diameter gold wires coated with redox polymer-"wired" glucose oxidase, they
      allowed tailoring of the glucose electrodes for > 2 nA/mM sensitivity; 0-30 mM
      dynamic range; drift of < or =5% per 24 h at 37 degrees C at 15 mM glucose
      concentration; and < or =5% current increment by the combination of 0.1 mM
      ascorbate, 0.2 mM acetaminophen, and 0.5 mM urate. The membranes also retained
      transition metal ions that bound to and damaged the redox polymer "wiring" the
      enzyme. The electrodes were tested in the jugular veins and in the intrascapular
      subcutaneous region of anaesthetized and heparinized nondiabetic Sprague-Dawley
      rats, in which rapid changes of glycemia were forced by intravenous injections of
      glucose and insulin. After one-point in vivo calibration of the electrodes, all
      of the 152 data points were clinically accurate when it was assumed that after
      insulin injection the glycemia in the subcutaneous fluid lags by 9 min behind
      that of blood withdrawn from the insulin-injected vein.

PMID- 10959962
TI  - In vivo determination of the molecular composition of artery wall by
      intravascular Raman spectroscopy.
AB  - Atherosclerotic plaque vulnerability is suggested to be determined by its
      chemical composition. However, at present there are no in vivo techniques
      available that can adequately type atherosclerotic plaques in terms of chemical
      composition. Previous in vitro experiments have shown that Raman spectroscopy can
      provide such information in great detail. Here we present the results of in vitro
      and in vivo intravascular Raman spectroscopic experiments, in which dedicated,
      miniaturized fiber-optic probes were used to illuminate the blood vessel wall and
      to collect Raman scattered light. The results make clear that an important hurdle
      to clinical application of Raman spectroscopy in atherosclerosis has been
      overcome, namely, the ability to obtain in vivo intravascular Raman spectra of
      high quality. Of equal importance is the finding that the in vivo intravascular
      Raman signal obtained from a blood vessel is a simple summation of signal
      contributions of the blood vessel wall and of blood. It means that detailed
      information about the chemical composition of a blood vessel wall can be obtained
      by adapting a multiple least-squares fitting method, which was developed
      previously for the analysis of in vitro spectra, to account for signal
      contributions of blood.

PMID- 10959963
TI  - Total internal reflection fluorescence and electrocapillary investigations of
      adsorption at a H2O-dichloroethane electrochemical interface. 1. Low-frequency
      behavior
AB  - Total internal reflection fluorescence and electrocapillary measurements are
      employed to provide complementary potential-dependent information about the
      mechanical and photophysical properties of the interface between two immiscible
      electrolyte solutions, 1,2-dichloroethane-H2O. Adsorption of the zwitterionic
      amphiphile, di-N-butylaminonaphthylethenylpyridiniumpropylsulfonate (I) produces
      an interface with mechanical (interfacial tension) and charge transport
      properties qualitatively like the unmodified interface. Addition of
      dilauroylphosphatidylcholine (DLPC) to the organic phase produces an interface
      dominated by DLPC adsorption and drastically alters the potential dependence of
      the interfacial tension, gamma, the interfacial excess populations, GammaI, the
      charge transport, and the fluorescence response from I. This result is explained
      in terms of a potential-dependent protonation of the DLPC at the interface, which
      causes it to desorb, and a competition for interfacial sites between DLPC and
      protonated and unprotonated dye I. Protonation of DLPC results in a rise in
      gamma, which is correlated with an increase in transport of the organic-phase
      anion tetraphenylborate, TPB-, and an increase in interfacially excited
      fluorescence from I. Both results are explained by a model in which the
      mechanical properties of the interface, as determined by the interfacial DLPC
      population, direct the ability of other species to transfer across TPB- or adsorb
      to I the interface.

PMID- 10959964
TI  - Biosensors based on membrane-bound enzymes immobilized in a 5-(octyldithio)-2
      nitrobenzoic acid layer on gold electrodes.
AB  - Gold electrodes were modified through chemisorption of 5-(octyldithio)-2
      nitrobenzoic acid (ODTNB). ODTNB includes a long chain in a short-length thio
      acid, providing a heterogeneous-like alkanethiol layer after adsorption on gold
      electrodes. Membrane-bound enzymes, in particular D-fructose dehydrogenase (FDH),
      D-gluconate dehydrogenase (GADH), and L-lactic dehydrogenase (cytochrome b2)
      (Cyb2), were immobilized onto ODTNB-modified gold electrodes simply by
      adsorption. The short-length thio acid may provide electrostatic interactions
      with enzyme surface charges, while the alkanethiolate enables hydrophobic
      interaction with the largely lipophilic, membrane-bound enzymes. The
      immobilization of FDH, GADH, and Cyb2 onto ODTNB-modified gold surfaces has been
      studied with the quartz crystal microbalance (QCM). Spectrophotometric and
      electrochemical assays indicate that the immobilized enzyme retains its enzymatic
      activity after immobilization onto the ODTNB-modified gold surface. The amount of
      immobilized (and active) enzyme was estimated from QCM to be of the order of 2.5
      x 10(-12)-5.3 x 10(-12) mol x cm(-2). A fructose biosensor was developed, making
      use of a gold surface modified with ODTNB and fructose dehydrogenase, employing
      hydroxymethylferrocene as a mediator in solution. Calibration curves exhibited a
      linear relation between the biosensor response and the substrate concentration up
      to 0.7 mM. Statistical analysis gave an excellent linear correlation (r = 0.9993)
      and a sensitivity of 6.1 mM(-1) fructose. The biosensor shows a significant
      stable catalytic current for at least 25 days.

PMID- 10959965
TI  - Standard electrochemical behavior of high-quality, boron-doped polycrystalline
      diamond thin-film electrodes
AB  - Standard electrochemical data for high-quality, boron-doped diamond thin-film
      electrodes are presented. Films from two different sources were compared (NRL and
      USU) and both were highly conductive, hydrogen-terminated, and polycrystalline.
      The films are acid washed and hydrogen plasma treated prior to use to remove
      nondiamond carbon impurity phases and to hydrogen terminate the surface. The
      boron-doping level of the NRL film was estimated to be in the mid 1019 B/cm3
      range, and the boron-doping level of the USU films was approximately 5 x 10(20)
      B/cm(-3) based on boron nuclear reaction analysis. The electrochemical response
      was evaluated using Fe-(CN)6(3-/4-), Ru(NH3)6(3+/2+), IrCl6(2-/3-), methyl
      viologen, dopamine, ascorbic acid, Fe(3+/2+), and chlorpromazine. Comparisons are
      made between the apparent heterogeneous electron-transfer rate constants,
      k0(app), observed at these high-quality diamond films and the rate constants
      reported in the literature for freshly activated glassy carbon. Ru(NH3)6(3+/2+),
      IrCl6(2-/3-), methyl viologen, and chlorpromazine all involve electron transfer
      that is insensitive to the diamond surface microstructure and chemistry with
      k0(app) in the 10(-2)-10(-1) cm/s range. The rate constants are mainly influenced
      by the electronic properites of the films. Fe(CN)6(3-/4-) undergoes electron
      transfer that is extremely sensitive to the surface chemistry with k0(app) in the
      range of 10(-2)-10(-1) cm/s at the hydrogen-terminated surface. An oxygen surface
      termination severely inhibits the rate of electron transfer. Fe(3+/2+) undergoes
      slow electron transfer at the hydrogen-terminated surface with k0(app) near 10(
      5) cm/s. The rate of electron transfer at sp2 carbon electrodes is known to be
      mediated by surface carbonyl functionalities; however, this inner-sphere,
      catalytic pathway is absent on diamond due to the hydrogen termination. Dopamine,
      like other catechol and catecholamines, undergoes sluggish electron transfer with
      k0(app) between 10(-4) and 10(-5) cm/s. Converting the surface to an oxygen
      termination has little effect on k0(app). The slow kinetics may be related to
      weak adsorption of these analytes on the diamond surface. Ascorbic acid oxidation
      is very sensitive to the surface termination with the most negative Ep(ox)
      observed at the hydrogen-terminated surface. An oxygen surface termination shifts
      Ep(ox) positive by some 250 mV or more. An interfacial energy diagram is proposed
      to explain the electron transfer whereby the midgap density of states results
      primarily from the boron doping level and the lattice hydrogen. The films were
      additionally characterized by scanning electron microscopy and micro-Raman
      imaging spectroscopy. The cyclic voltammetric and kinetic data presented can
      serve as a benchmark for research groups evaluating the electrochemical
      properties of semimetallic (i.e., conductive), hydrogen-terminated,
      polycrystalline diamond.

PMID- 10959966
TI  - Oriented immobilization of antibodies onto the gold surfaces via their native
      thiol groups.
AB  - The general approach for site-oriented immobilization of antibodies onto gold
      supports is reported. The immobilization is carried out using the native sulfide
      groups of immunoglobulin (IgG). To liberate the thiol groups, the intact IgG was
      split into two half-IgG fragments without destruction of the binding site of the
      antibody. The immobilization of half-IgG fragments on the gold surface was
      carried out by simple adsorption. The antigen binding capacity of the half-IgG
      modified gold supports is similar to that of the gold surfaces with the
      traditionally linked antibodies and is much higher than for nonspecifically
      adsorbed intact IgGs. The immobilized antibodies, according to the proposed
      approach, maintain high antigen binding constants. The immobilization procedure
      provides orientation of IgG fragments in terms of the similar distance between
      the binding site of the antibody and the surface of the gold support, which does
      not cause the distribution of the apparent affinity constants. The high
      operational stability of half-IgG modified gold electrodes makes them applicable
      for analytical applications.

PMID- 10959967
TI  - Gas sampling glow discharge: a versatile ionization source for gas chromatography
      time-of-flight mass spectrometry
AB  - A gas chromatograph has been coupled to a direct-current gas sampling glow
      discharge (GSGD) ionization source for the mass spectrometric analysis of
      halogenated hydrocarbons. The continuous discharge is contained within the first
      vacuum stage of the differentially pumped spectrometer interface. The discharge
      can be operated statically or rapidly switched between atomic and molecular
      ionization modes; both atomic and molecular spectra could be generated in the
      helium-supported plasma. In the switched configuration, the duty cycle is 50% for
      each mode. The ionization mode is selected by application of either a positive
      (molecular) or negative (atomic) potential to the sample introduction electrode,
      and the two kinds of spectra can be sequentially collected by changing the
      voltage and current between two preset values. Similar ion-optical voltage
      settings could be employed for both modes of operation, with the exception of the
      steering-plate potential, which had to be modulated between two different values
      (at the plasma switching frequency) to obtain the greatest atomic and molecular
      signal levels. The source is capable of generating mass spectra resembling those
      from an electron-impact source while operated in the molecular ionization mode
      (both static and dynamic). The best atomic detection limits (1-25 fg of analyte/
      second) were obtained when the plasma was operated in the static mode with single
      channel gated ion counting. Atomic detection limits obtained with boxcar averager
      data collection were comparable for static and switched operation of the source
      (1-30 pg/s). Likewise, the molecular detection limits were similar for the static
      and switched modes and span the range of 7-140 pg/s (boxcar averagers). Precision
      was better than 7% RSD under all conditions. The atomic and molecular
      chromatographic peak heights were nearly unchanged over a range of modulation
      rates from 5 to 100 Hz. The elemental ratio (35Cl+/12C+) for chloroform was also
      measured over a range of plasma modulation rates (5-90 Hz) and found to be
      randomly distributed about the sample mean. Several chlorinated hydrocarbons were
      introduced into the discharge and could be successfully differentiated (or
      speciated) on the basis of their 35Cl+/12C+ ratios.

PMID- 10959969
TI  - Determination of glyphosate and aminomethylphosphonic acid residues in water by
      gas chromatography with tandem mass spectrometry after exchange ion resin
      purification and derivatization. Application on vegetable matrixes
AB  - An analytical method for the determination of glyphosate and its principal
      metabolite, aminomethylphosphonic acid (AMPA), in water of different hardnesses
      (5, 20, and 30 degrees DH, french hardness) has been developed. Samples were
      fortified at different levels (0.05, 0.1, 1, and 5 microg/L) and were purified by
      column chromatography on ion-exchange resins. After derivatization with TFAA/HFB
      mixture, the derivatives were quantified by using capillary gas chromatography
      with an ion-trap tandem mass spectrometric detector. Analytical conditions for
      MS/MS detection were optimized, and the quantification was carried out on the sum
      of areas of the three most representative ions: m/z 283, 223, and 181 for AMPA
      and m/z 440, 321, and 261 for glyphosate. The limit of quantification was
      demonstrated to be at 0.05 microg/L for each compound. The mean recovery value
      and the relative standard deviation (n = 65) were 93 and 12% for AMPA and 95 and
      13% for glyphosate.

PMID- 10959968
TI  - Effects of molecular oxygen on multiphoton-excited photochemical analysis of
      hydroxyindoles.
AB  - We have examined the effects of dissolved molecular oxygen on multiphoton-excited
      (MPE) photochemical derivatization of serotonin (5HT) and related cellular
      metabolites in various buffer systems and find that oxygen has a profound effect
      on the formation efficiency of visible-emitting photoproducts. Previously, end
      column MPE photoderivatization provided low mass detection limits for capillary
      electrophoretic analysis of hydroxyindoles, but relied on the use of Good's
      buffers to generate high-sensitivity visible signal. In the present studies,
      visible emission from 5HT photoderivatized in different buffers varied by 20-fold
      under ambient oxygen levels but less than 2-fold in the absence of oxygen; oxygen
      did not significantly alter the photoproduct excited-state lifetime
      (approximately 0.8 ns). These results support a model in which oxygen interferes
      with formation of visible-emitting photoproducts by quenching a reaction
      intermediate, an effect that can be suppressed by buffer molecules. Deoxygenation
      of capillary electrophoresis separation buffers improves mass detection limits
      for 5-hydroxyindoles fractionated in 600-nm channels by approximately 2-fold to <
      or =30000 molecules and provides new flexibility in identifying separation
      conditions for resolving 5HT from molecules with similar electrophoretic
      mobilities, such as the catecholamine neurotransmitters.

PMID- 10959970
TI  - Glow discharge ionization source for liquid chromatography/particle beam mass
      spectrometry
AB  - A detailed evaluation of the analytical characteristics of a liquid
      chromatography/particle beam-glow discharge mass spectrometry (LC/PB-GDMS) system
      is described for applications in the area of inorganic (free metals in solution)
      and organic compound analysis. A highly efficient particle beam interface is used
      to introduce analyte species into a glow discharge source for subsequent
      vaporization and ionization. The GD operating current and gas pressure were
      optimized, with the general responses found to be similar to those obtained
      previously for particulate matter analysis by this PB-GDMS system. The mass
      spectra obtained for inorganic species are comprised exclusively of the
      respective elements' isotopic patterns, with no evidence of appreciable oxide
      species formation. Organic species introduced into the discharge through the
      particle beam interface yield mass spectra that are virtually identical to those
      from standard electron impact (70 eV) ionization. An analytical response curve
      for caffeine, using 200-microL (H2O/MeOH) injection volumes, showed less than 5%
      RSD for replicate injections over a concentration range of 10-500 ppm, with a
      detection limit of 13 ppb (2.7 ng) obtained for the caffeine molecular ion.
      Similarly, detection limits for Fe, Ag, and Cs ranged from 5.8 to 6.1 ppb
      (approximately 1 ng, each) in the injected volume. As an example of the
      feasibility of the PB-GDMS system as a detector for liquid chromatography, the
      separation and identification of the organic constituents in diet soda was
      performed.

PMID- 10959971
TI  - An efficient liquid chromatography--mass spectrometry interface for the
      generation of electron ionization spectra
AB  - The use of a new LC-MS interface (cap-EI), part of a Waters Integrity system,
      capable of generating EI spectra at micro flow rates is presented. The cap-EI
      interface relies on the production of a fine aerosol by means of a nebulizer and
      supported by a nitrogen jet. Sensitivity, response linearity, reproducibility,
      and LC compatibility of the interface were thoroughly examined using
      testosterone, caffeine, a mixture of antiinflammatory drugs, and 3,4
      dihydroxybenzoic acid as test compounds. The interface is fully compatible with
      LC requirements such as high-water- and/or -buffer-content mobile phases.
      Reproducibility, high sensitivity in scan mode, as well, to produce library
      searchable EI spectra, 2 orders of magnitude linearity, together with an
      intrinsic simplicity of the entire system are the key features of cap-EI
      interface.

PMID- 10959972
TI  - Structural analysis of polymer end groups by electrospray ionization high-energy
      collision-induced dissociation tandem mass spectrometry
AB  - Chemical structures of polymer end groups play an important role in determining
      the functional properties of a polymeric system. We present a mass spectrometric
      method for determining end group structures. Polymeric ions are produced by
      electrospray ionization (ESI), and they are subject to source fragmentation in
      the ESI interface region to produce low-mass fragment ions. A series of source
      fragment ions containing various numbers of monomer units are selected for high
      energy collision-induced dissociation (CID) in a sector/time-of-flight tandem
      mass spectrometer. It is shown that high-energy CID spectra of source-induced
      fragment ions are very informative for end group structure characterization. By
      comparing the CID spectra of fragment ions with those of known chemicals, it is
      possible to unambiguously identify the end group structures. The utility of this
      technique is illustrated for the analysis of two poly(ethylene glycol)-based slow
      releasing drugs where detailed structural characterization is of significance for
      drug formulation, quality control, and regulatory approval. Practical issues
      related to the application of this method are discussed.

PMID- 10959973
TI  - Evaluation of cyclooxygenase-2 inhibitors using pulsed ultrafiltration mass
      spectrometry.
AB  - Since selective inhibition of the inducible form of cyclooxygenase (COX-2) might
      retain all the benefits of classical nonsteroidal antiinflammatory agents while
      avoiding the major side effects associated with inhibition of the constitutive
      isoform COX-1, COX-2 has become an important target for the discovery and
      development of new antiinflammatory drugs. To aid in the discovery and
      characterization of such selective inhibitors, we have applied a mass
      spectrometry-based screening technique, pulsed ultrafiltration mass spectrometry,
      using COX-2 as the target. In a blind study, 18 samples enriched with one or more
      inhibitors of COX-2 were evaluated. The matrixes for the test samples consisted
      of DMSO, r DMSO solutions of a plant extract, or a bacterial fermentation broth
      extract. The composition of the samples was unknown during the assays, as were
      the concentrations of the COX-2 inhibitors. A soluble recombinant form of human
      COX-2 was incubated with each sample, and then an aliquot of each mixture was
      injected into the stirred ultrafiltration chamber fitted with a 30000 MW cutoff
      ultrafiltration membrane. After the unbound and weakly bound compounds were
      washed away, the ligand-receptor complexes were disrupted using an acidified 10%
      methanol solution. The released ligands were trapped on a C18 cartridge and then
      identified using liquid chromatography-negative ion electrospray mass
      spectrometry with the trapping cartridge as the HPLC column. Neither the plant
      matrix nor the fermentation broth extract were found to interfere with the assay.
      Two or three ligands for COX-2 were identified in each sample, which included
      polar and nonpolar compounds and inhibitors with IC50 values ranging from 100
      microM to 10 nM.

PMID- 10959974
TI  - Improvement of resolution, mass accuracy, and reproducibility in reflected mode
      DE-MALDI-TOF analysis of DNA using fast evaporation--overlayer sample
      preparations.
AB  - DNA analysis by matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry is hindered by two processes: alkali metal adduction and
      fragmentation of the intact ionized molecule. The adverse effects of both
      processes can be reduced by adding ammonium ion salts or compounds such as
      fructose to the sample preparations. Matrix additives improve sensitivity and
      resolution of DNA analysis by MALDI. In addition, spot-to-spot reproducibility,
      resolution, and mass accuracy for DNA oligonucleotides (< or = 12 mer) can be
      improved by the use of overlayer sample preparations with matrixes that have low
      aqueous solubilities, such as alpha-cyano-4-hydroxycinnamic acid, ferulic acid,
      and 2,4,6-trihydroxyacetophenone. For example, resolution for 5-12-mer
      oligonucleotides is greater than 7000 using overlayer matrix preparations and
      mass accuracy values are well below 20 ppm. In addition to these methods, a new
      method for analyzing DNA in positive ion mode is reported using acidified 3
      hydroxypicolinic acid. This method does not lose sensitivity for higher mass
      oligonucleotides as quickly as overlayer methods, and spectra retain > 6000
      resolution and mass accuracies of approximately 20 ppm between different
      overlayer depositions.

PMID- 10959976
TI  - Determination of main and minor components of silicon based materials by a
      combustion with elemental fluorine. Separation of gaseous fluorination products
      by carrier gas distillation and gas mass spectrometry
AB  - For the determination of main and minor components in silicon-based ceramic
      powders, a decomposition by a combustion with elemental fluorine and separation
      of the volatile fluorination products by a carrier-gas distillation with a
      subsequent detection by quadrupole mass spectrometry is described. The necessity
      and success of the separation step is demonstrated for the determination of boron
      as a minor constituent in SiC, where the spectral interferences of silicon on the
      boron signals are decreased considerably. The method developed is shown to be
      directly applicable to determination of silicon in Si3N4, SiC, and SiO2. The
      determination of nitrogen in Si3N4 requires additional effort, to separate
      nitrogen from the excess of fluorine. For the determination of boron, a complete
      mobilization of BF3 is assured by the presence of an adequate amount of GeF4.
      Analysis results obtained with different types of calibration show a precision of
      30 microg for boron at the milligram-per-gram level and a precision between 0.5
      and 2% (m/m) for the main components, silicon and nitrogen. Within these standard
      deviations, the results agree well with the values expected from the
      stoichiometry, with the results for silicon and boron obtained by wet chemical
      decomposition and slurry techniques in combination with ICP-OES and with the
      results for nitrogen obtained by carrier gas heat extraction.

PMID- 10959975
TI  - Peptide profiling of cells with multiple gene products: combining immunochemistry
      and MALDI mass spectrometry with on-plate microextraction.
AB  - Due to the intracellular chemical complexity and a wide range of transmitter
      concentrations, the detection of the complete set of peptide transmitters in a
      single cell is problematic. In the current study, a multidisciplinary approach
      combining single-cell MALDI-MS peptide profiling, northern analysis, in situ
      hybridization, and immunocytochemistry allows characterization of a more complete
      set of neurotransmitters than individual approaches in the Aplysia californica B1
      and B2 motor neurons. Because different results were obtained using both in situ
      and immunohistochemical techniques compared to previous reports, MALDI-MS assays
      have been used to examine CP1-related gene products in these cells. However,
      MALDI with standard sample preparation does not detect the presence of the CP1
      gene products. A novel on-plate microextraction approach using concentrated MALDI
      matrix 2,5-dihydroxybenzoic acid with a mixture of acetone and water as the
      solvent has been developed to allow the detection of trace-level gene expression
      products. Both neuropeptide precursors in the B1 and B2 neurons-the SCP and CP1
      prohormones-end with large peptides that have multiple cysteine residues. For
      SCP, MALDI-MS verifies the presence of a novel 9325 Da SCP-related peptide. In
      the case of CP1, a disulfide-bonded homodimer is detected and the disulfide
      bonding pattern elucidated using MALDI-MS coupled with on-plate enzymatic
      digestion.

PMID- 10959977
TI  - Free flow electrophoresis device for continuous on-line separation in analytical
      systems. An application in biochemical detection.
AB  - A free flow electrophoresis (FFE) device was developed for continuous
      electrophoretic separation of charged compounds and implemented in a continuous
      flow biochemical detection (BCD) system. These continuous separation
      characteristics make FFE well suitable for online implementation in a
      chromatographic or flow injection analysis system, in which an additional
      separation step of charged compounds is desired. In a heterogeneous biochemical
      flow assay for the determination of biotin, an analyte zone reacts with an excess
      of an affinity protein. Subsequently, the free binding sites of the affinity
      protein react with an excess of fluorescein-labeled ligand. Free and affinity
      protein-bound label are separated on the FFE device prior to fluorescence
      detection of the separated fractions. Biotin and streptavidin were chosen as,
      respectively, model ligand and affinity protein. Since all the compounds that are
      involved possess different electrophoretic properties, quantitative analysis is
      performed after completely separating the fluorescent affinity complex and
      labeled biotin in the FFE device within 2 min. Since the device is optically
      transparent, the separated zones can be detected in the separation compartment,
      using laser-induced fluorescence. The applicability of the BCD-FFE system in
      combination with a HPLC separation is demonstrated in the bioanalysis of biotin
      in human urine at the micromole per liter level.

PMID- 10959978
TI  - GR 24 enantiomers: synthesis, NMR spectroscopy, X-ray crystallography, and
      separation by chiral electrokinetic capillary chromatography.
AB  - Chiral discrimination of enantiomers of 2-methyl-4-(2-oxo-2,3,3a,8b-tetrahydro-4H
      indeno[1,2b]furan-3-yl-iden emethoxy)but-2-en-4-olide (commonly referred to as GR
      24) by three polymeric chiral surfactants (PCS) is studied by use of chiral
      polymeric surfactant capillary electrophoresis (CPSCE). The CPSCE results
      indicate that the optical configurations of valine residues on the PCS backbone
      affect chiral resolution and elution order of GR24 stereoisomers. The L- and D
      forms of poly(sodium N-undecanoyl valinate) provide baseline separation of all
      four enantiomers while the DL-form separates diastereomers of GR 24 (1). A model
      is presented rationalizing the migration behavior and chiral resolution of 1 in
      CPSCE. The actual configuration of the stereogenic centers of GR 24 and 3-[(2,5
      dihydro-3-methyl-2-oxo-5-furanyl)oxo]-methylene-3,3a,6,6a-tetrah ydro-2H
      cyclopenta[b]furan-2-one (GR 7) is established by a concerted application of high
      resolution nuclear magnetic resonance spectroscopy and X-ray crystallography.

PMID- 10959979
TI  - The influence of temperature on the characterization of water-soluble polymers
      using asymmetric flow field-flow-fractionation coupled to multiangle laser light
      scattering
AB  - Asymmetrical flow field-flow fractionation coupled to multiangle laser light
      scattering has been shown to be an effective method to determine the molar mass
      distribution of polysaccharides. Two polymer standards, dextran and pullulan,
      were analyzed in the temperature range 30-60 degrees at intervals of 10 degrees
      C. The weight average molar mass and molar mass distribution obtained at each
      temperature agreed well with quoted values. The diffusion coefficient,
      hydrodynamic radius, radius of gyration, and activation energy of diffusion were
      calculated and all agreed well with literature data obtained by dynamic and
      static light scattering. The asymmetry factor Rg/Rh suggests a flexible random
      coil conformation for both polymers, which was supported by the molar mass
      dependence of both the radius of gyration and the hydrodynamic radius. The
      results show the potential of asymmetric flow field fractionation coupled to
      multiangle laser light scattering in undertaking measurements of molar mass
      distribution as a function of temperature.

PMID- 10959980
TI  - Determination of sugar compounds in olive plant extracts by anion-exchange
      chromatography with pulsed amperometric detection.
AB  - We describe a chromatographic method that uses isocratic elution and pulsed
      amperometric detection to determine soluble carbohydrates in plant tissues. Such
      a method provides a rapid and convenient means to obtain a complete profile of
      the sugar components of leaves and roots from olive (Olea europaea L. cv.
      Coratina) plants. A simple purification of plant extracts using pure water was
      developed, which is far less time-consuming and retains a high level of accuracy.
      Excellent separation of myo-inositol, galactinol, mannitol, galactose, glucose,
      fructose, sucrose, raffinose, and stachyose was achieved with an anion-exchange
      column and 12 mM NaOH spiked with 1 mM barium acetate as an eluent. At a flow
      rate of 1.0 mL/min, the time of analysis was less than 25 min, and repeatability
      of the method on the order of 2.2% as RSD or better for retention times and lower
      than 5.2% for peak areas. Recoveries approximated 100% (range 97.2-104.5%), and
      the method provided good precision with a coefficient of variation which ranged
      between 0.9 and 3.3%. Among identified carbohydrates extracted from leaves and
      roots of olive plants, glucose and mannitol were major compounds. Their molar
      ratio was estimated to be 1.2+/-0.1 and 2.2+/-0.3 for olive leaves and roots,
      respectively. The occurrence of soluble galactinol in plant tissues was also
      validated.

PMID- 10959981
TI  - Retention mechanism of beta-blockers on an immobilized cellulase. Relative
      importance of the hydrophobic and ionic contributions to their enantioselective
      and nonselective interactions.
AB  - The adsorption isotherms of the enantiomers of three beta-blockers, metoprolol,
      alprenolol, and propranolol, were measured on cellobiohydrolase I (CBH I)
      immobilized on silicagel, in the concentration range between 0.25 microM and 1.7
      mM, at pH = 5.0, 5.5, and 6.0. In agreement with previous results, these data are
      accounted for by a two-sites physical model and fit closely to a Bilangmuir
      equation. The saturation capacities and the binding constants were determined for
      each enantiomer on the chiral and the nonchiral sites. The chiral sites are shown
      to be strongly ionic, in contrast to the nonchiral ones, which are mainly
      hydrophobic. However, the chiral binding of (S)-propranolol is endothermic, with
      a high adsorption entropy, in contrast to the chiral interactions of (R)
      propranolol and to the nonchiral interactions, which are all exothermic. This
      indicates that hydrophobic interactions also play a role in the chiral binding.
      The dependence of the adsorption parameters on the hydrophobicity of the solute
      is discussed and interpreted in terms of the retention mechanism. The results are
      compared with the structure of the protein, recently elucidated by X-ray
      crystallography.

PMID- 10959982
TI  - Supercritical fluid extraction and accelerated solvent extraction of dioxins from
      high- and low-carbon fly ash
AB  - This study investigates the replacement of Soxhlet extraction by supercritical
      fluid extraction (SFE) or accelerated solvent extraction (ASE) for the removal of
      dioxins from municipal waste incinerator fly ash. SFE is very matrix dependent;
      higher percent recoveries versus Soxhlet extraction can be obtained for low
      carbon-level fly ash, but only a few percent of dioxins can be extracted from
      high-carbon-level fly ash. The addition of large quantities of toluene in the
      extraction cell prior to extraction of high-carbon fly ash improves the recovery
      of the lowest chlorinated dioxins (approximately 90%), but a maximum of 20% of
      the octachlorodibenzo-p-dioxins can be extracted. Since large quantities of
      toluene are needed to improve the recoveries, ASE with toluene was tested.
      Recoveries similar to Soxhlet extraction can be obtained in 2 h at 80 degrees C.
      Increasing the temperature to 150 degrees C increases the extraction rate and
      yields recoveries of approximately 110-160% compared to 48-h Soxhlet extraction
      for all congeners for both low- and high-carbon fly ashes. These results question
      the choice of Soxhlet extraction as a reference method for dioxin determination.

PMID- 10959983
TI  - Reversed-phase high-performance liquid chromatography combined with on-line UV
      diode array, FT infrared, and 1H nuclear magnetic resonance spectroscopy and time
      of-flight mass spectrometry: application to a mixture of nonsteroidal
      antiinflammatory drugs.
AB  - A prototype multiply hyphenated system has been applied to the analysis of a
      mixture of nonsteroidal antiinflammatory drugs separated by reversed-phase HPLC.
      Characterization of the model NSAIDs was achieved via a combination of diode
      array UV, 1H NMR, FT-IR spectroscopy, and time-of-flight mass spectrometry. This
      combination of spectrometers allowed the collection of UV, 1H NMR, IR, and mass
      spectra together with atomic composition data enabling almost complete structural
      characterization to be performed.

PMID- 10959984
TI  - Model for nonequilibrium binding and affinity chromatography: characterization of
      8-hydroxyquinoline immobilized on controlled pore glass using a flow injection
      system with a packed microcolumn
AB  - This paper discusses the use of pulse techniques for analysis of zonal elution
      data for the determination of mass-transfer and axial dispersion constants for
      porous support materials with adsorption to the surface or to a surface-bonded
      phase. As an example, this paper considers the case of controlled pore glass
      (CPG) with a bonded phase that is used with microcolumns and a flow injection
      analysis system. For the CPG, axial dispersion in the form of eddy mixing can be
      described by l = 0.203, and the overall mass-transfer term, K(OL) = 3.9 x 10(-6)
      cm/s. Additionally, an affinity chromatography model was adapted to effectively
      describe systems employing CPG as the support material through modification of
      equations describing typical affinity chromatography systems and by inclusion of
      an axial dispersion term in the calculation of N. This model was used to predict
      breakthrough curves for cadmium adsorption by 8-hydroxyquinolinol immobilized on
      CPG packed in microcolumns. In general, the information from the model can be
      used to extract equilibrium-based constants (binding strengths and site
      capacities) from a nonequilibrium flow system. The data and model can also be
      employed in determining the performance for scaled-up extraction systems. The
      modified model is available in EXCEL spreadsheet format as Supporting
      Information.

PMID- 10959985
TI  - Selective trace enrichment of chlorotriazine pesticides from natural waters and
      sediment samples using terbuthylazine molecularly imprinted polymers
AB  - Two molecularly imprinted polymers were synthesized using either dichloromethane
      or toluene as the porogen and terbuthylazine as the template and were used as
      solid-phase extraction cartridges for the enrichment of six chlorotriazines
      (deisopropylatrazine, deethylatrazine, simazine, atrazine, propazine, and
      terbuthylazine) in natural water and sediment samples. The extracted samples were
      analyzed by liquid chromatography/diode array detection (LC/DAD). Several washing
      solvents, as well as different volumes, were tested for their ability to remove
      the matrix components nonspecifically adsorbed on the sorbents. This cleanup step
      was shown to be of prime importance to the successful extraction of the
      pesticides from the aqueous samples. The optimal analytical conditions were
      obtained when the MIP imprinted using dichloromethane was the sorbent, 2 mL of
      dichloromethane was used in the washing step, and the preconcentrated analytes
      were eluted with 8 mL of methanol. The recoveries were higher than 80% for all
      the chlorotriazines except for propazine (53%) when 50- or 100-mL groundwater
      samples, spiked at 1 microg/L level, were analyzed. The limits of detection
      varied from 0.05 to 0.2 microg/L when preconcentrating a 100-mL groundwater
      sample. Natural sediment samples from the Ebre Delta area (Tarragona, Spain)
      containing atrazine and deethylatrazine were Soxhlet extracted and analyzed by
      the methodology developed in this work. No significant interferences from the
      sample matrix were noticed, thus indicating good selectivity of the MIP sorbents
      used.

PMID- 10959986
TI  - Development of a multichannel fluorescence affinity sensor system
AB  - A multichannel fluorometer is proposed for analysis of biochemical reactions. The
      sensor is based on the luminescence generation in the evanescent field of a
      totally reflected laser beam. For transduction, multiple reflection elements are
      used. Multichannel operation is realized, including the possibility of applying
      different solutions to each channel at the same time. First experimental results,
      obtained with fluorescein or Cy5 as labels in a model hybridization assay,
      demonstrate the applicability and allow the detection of 3-10 fmol injected
      fluorescently labeled oligonucleotide.

PMID- 10959987
TI  - Airflow rate in the quantitation of volatiles in air streams by solid-phase
      microextraction
AB  - A previously reported method for nonequilibrium quantitation of air-borne
      volatiles from air streams by solid-phase microextraction (SPME) was improved by
      broadening its scope. The original method was defined for the 100-microm
      poly(dimethylsiloxane) fiber type for a wide range of analytes, sampling
      temperatures, and sampling times, but only for four specific airflow
      configurations. The present study extends the choice of volumetric airflow rates
      to a continuous range between 2 and 220 mL/min. Kinetics of absorption was
      characterized for 21 different airflow rates within this range using n-alkanes of
      11-18 carbons. Nonlinear regression analysis was used to develop a relationship
      between airflow rate and absorption kinetics and then to integrate these results
      into the previous model. The overall model (with 8 fitted degrees of freedom and
      based on 2240 measurements) had an r2 value of 0.9972 and residual variability
      (RSD) of 9.75%, which compared favorably with the sampling precision of SPME
      (approximately 5%). The method allows absolute quantitation by SPME for a broad
      range of analytes and sampling parameters without prior calibration of the
      individual fiber and regardless of whether equilibration is complete. Simulations
      are presented that demonstrate how the choice of airflow rate can affect
      quantitation.

PMID- 10959988
TI  - Use of a microplate scintillation counter as a radioactivity detector for
      miniaturized separation techniques in drug metabolism.
AB  - In miniaturized separation techniques, such as capillary electrophoresis (CE) or
      capillary liquid chromatography (LC), conventional on-line radioactivity
      detection of labeled compounds is restricted, because of insufficient
      sensitivity. It will be shown that a microplate scintillation counter for 96-well
      plates (TopCount) can be used as a sensitive and easy-to-handle radioactivity
      detector for capillary LC and CE. The attractive combination of capillary LC,
      eluent fractionation, and subsequent off-line counting is described. The new
      method is applied for rapid and sensitive separation and detection of 3H-labeled
      parent drug and its metabolites at levels between 25 and 700 cpm in rat urine.
      The advantages of capillary LC coupled to the TopCount, and combined with LC-MS
      data, can be of benefit in many analytical areas, including the characterization
      of metabolites at low concentration within complex biological fluids. With the
      same setup, the fractionation with subsequent off-line counting is equally
      applicable to CE. This is demonstrated with electrophoretically separated 14C
      labeled impurities, nicely resolved from a negatively charged main compound, at
      low levels.

PMID- 10959989
TI  - Solid-phase extraction of technetium--amine complexes onto C18 silica and its
      application to the isolation of 99Tc
AB  - The extraction of Tc-tripentylamine complexes onto C18 silica solid-phase
      extraction columns is evaluated for the selective removal of 99Tc from other
      isotopes. The Tc-amine complex is quantitatively extracted from sulfuric acid and
      can be recovered from the column by elution with dilute alkali. A clean
      separation of Tc from all likely contaminants, including Ru, is achieved showing
      that C18 silica solid-phase extraction columns are a viable and attractive
      alternative to the solvent extraction of 99Tc.

PMID- 10959990
TI  - The cruciate ligaments in total knee arthroplasty: a kinematic analysis of 2
      total knee arthroplasties.
AB  - In vivo weight-bearing fluoroscopic kinematic analysis using an interactive model
      fitting technique with 3-dimensional computer-aided design solid models was done
      using 16 anterior and posterior (bicruciate)-sparing and 6 posterior cruciate
      sparing total knee arthroplasties (TKAs). All patients had a satisfactory
      clinical result with a minimum of 12 months' follow-up. The femorotibial contact
      position of TKAs started posterior to the midline in extension. Bicruciate TKAs
      revealed gradual posterior femoral rollback and limited anterior-posterior
      translation but remained posterior to the sagittal plane midline in all
      positions. Posterior cruciate-sparing TKAs began significantly posterior in
      extension, demonstrated progressive anterior translation with flexion, and had
      exaggerated medial condyle translation on deep knee bend. The posterior cruciate
      retaining TKAs of this study had the most abnormal kinematic performance.

PMID- 10959992
TI  - Windswept deformity in bilateral total knee arthroplasty.
AB  - Windswept deformity, when an individual has 1 knee in extreme varus alignment and
      the other in severe valgus alignment, is an unusual occurrence in patients
      presenting for bilateral total knee arthroplasty. This condition was evaluated in
      22 patients to examine possible differences between knees in the same individual.
      Differences between the varus and valgus knees included alignment (P = .0001), as
      expected, and the position of the lateral joint line (P = .0161) preoperatively.
      No significant differences were observed between these 2 knee categories in any
      other comparison preoperatively or postoperatively. Total knee arthroplasty in
      patients with windswept deformity can be expected to be successful in both knees
      when attention is given to proper alignment and soft tissue balancing
      intraoperatively.

PMID- 10959991
TI  - Cemented first-time revisions of the femoral component: prospective 7 to 13
      years' follow-up using second-generation and third-generation technique.
AB  - In a prospective, consecutive study of first-time cemented femoral revisions, 109
      hips were evaluated for a minimum of 7 years. There were 87 Charnley (18
      standard, 69 long), 21 Spectron (3 standard, 18 long), and 1 Brunswick long-stem
      arthroplasties. There was an increased risk for rerevision in younger patients (P
      = .0001) and with use of standard stems (P = .002). Factors of importance for
      development of mechanical failure were younger age (P = .0001), presence of more
      pronounced bone defects (P < .005), use of standard stems (P < .0005), and
      presence of radiolucencies on the postoperative radiographs (Gruen zones 4 and 6)
      (P < .01). Our results confirm that cemented femoral revisions are a durable
      option in elderly patients, when improved cementing techniques and long-stem
      prostheses are used.

PMID- 10959993
TI  - Drainage is of no use in primary uncomplicated cemented hip and knee arthroplasty
      for osteoarthritis: a prospective randomized study.
AB  - In a prospective, randomized study, 58 patients with primary cemented hip
      arthroplasty and 39 patients with primary cemented knee arthroplasty were divided
      into groups with postoperative closed-suction drainage and without drainage.
      There was no difference in healing of the wounds, postoperative blood
      transfusions, complications, or range of motion. Although there was more soaked
      dressing requiring reinforcements in the groups without drainage, as a result of
      this study, we no longer use drains in uncomplicated cemented primary hip and
      knee arthroplasties for osteoarthritis.

PMID- 10959994
TI  - Osteolysis in cemented titanium alloy hip prosthesis.
AB  - We evaluated 132 consecutively implanted cemented titanium alloy stems (Ti6-Al7
      Nb, SLS-88) after a mean follow-up of 6.6 years (range 5-7 years). Almost 30% of
      the stems showed significant osteolysis, mainly in the proximal stem area. The
      amount of osteolysis correlated significantly to a typical pain pattern: dull,
      circular, and occurring at rest. Six stems had already been revised, and another
      7 stems were loose clinically and radiologically, which resulted in a Kaplan
      Meier survivorship of 95% for stem revisions and 88% for stem failures (revisions
      plus loose stems). We found that smaller stem sizes tend to increase the
      development of osteolysis and loosening. Two factors seem to play a role in early
      loosening of cemented titanium alloy stems: i) increased elasticity of titanium,
      which leads in small stem sizes to micromotion between the stem and cement and to
      cement breakage, and ii) corrosion of the cemented titanium alloy stem and
      subsequent osteolysis in the adjacent bone. The combination of both factors (high
      elasticity plus corrosion) accelerates the degradation of the bone anchorage of
      the stem and initiates early loosening. We advise against the further use of
      cemented SLS-88 titanium alloy stems.

PMID- 10959995
TI  - Posterior stabilization in total knee arthroplasty with use of an ultracongruent
      polyethylene insert.
AB  - Fifty-three primary and 47 revision posterior cruciate ligament (PCL)
      substituting total knee arthroplasties (TKAs) using a highly conforming
      (ultracongruent) polyethylene insert were retrospectively reviewed over a 48- to
      106-month (mean, 60+/-11 months) follow-up period. These 100 knees were age and
      sex matched with another 100 TKAs performed using a PCL-sparing design. The
      ultracongruent design has an anterior buildup of 12.5 mm and a more conforming
      articular surface to match better the radius of the femoral component. In primary
      and revision TKAs, the average Hospital for Special Surgery knee score (P = .3)
      and range of motion (P = .43) were similar between the PCL-sparing and
      ultracongruent groups. In primary and revision TKAs, there were no revisions
      resulting from instability for patients receiving an ultracongruent insert versus
      5 knees in the PCL-sparing control group secondary to subsequent postoperative
      anteroposterior instability and PCL insufficiency.

PMID- 10959996
TI  - A stem design change to reduce peak cement strains at the tip of cemented total
      hip arthroplasty.
AB  - A series of 3-dimensional finite element models was created to assess different
      designs of the tip of the stems of cemented femoral components of total hip
      arthroplasty that would decrease the peak axial tensile cement strains developed
      near the tip. Features of stem design that would facilitate positioning the
      femoral component in a neutral position centered in uniform cement mantle of
      adequate thickness also were evaluated. These studies showed that a stem that had
      a narrow tip profile that would accept an externally applied polymethyl
      methacrylate centralizer shaped similar to a napkin ring and had a gradual
      transition zone to join the body of the implant achieved these objectives. Such a
      combination resulted in the reduction of the peak axial strains to less than half
      the magnitude of the peak strains around a conventional tip (830 vs 1,868
      microstrain). The reduction in peak axial strains was to one third the magnitude
      of the strains developed adjacent to a stem with a hole drilled into the tip to
      accept the commonly used fin-type polymethyl methacrylate centralizer (830 vs
      2,466 microstrain). These goals were achieved because a stem that is designed to
      accept a napkin ring-style centralizer i) has a lower bending stiffness at the
      tip of the implant, ii) allows room for a thicker cement mantle, and iii) avoids
      creating a stress riser adjacent to the edge of the drill hole. The peak cement
      strains adjacent to a stem of this design are well below the endurance limit of
      cement as long as the transition zone where the narrow tip meets the body of the
      implant is gradual.

PMID- 10959997
TI  - Patients' perception of pain after total hip arthroplasty.
AB  - A study was undertaken to determine the frequency with which patients had pain
      that they attributed to their hip after total hip arthroplasty. Pain drawings
      were used to allow patients to localize the area of their symptoms, and the
      degree of pain was quantified with visual analog scales. Complete clinical and
      radiographic data were collected on all patients so that the occurrence of pain
      could be correlated with a number of parameters previously reported to affect the
      incidence of pain, including age, sex, activity level, length of follow-up, stem
      size, bone type (Dorr index), and type of stem fixation (proximally coated, fully
      coated, or cemented). Results indicated that type of stem fixation was the only
      parameter statistically correlated with a higher incidence of thigh pain.
      Patients with proximally coated stems were more than twice as likely to complain
      of pain than patients with fully coated or cemented hips (P < .01). Although the
      incidence of thigh pain was significantly higher with proximally coated stems,
      the severity was not, averaging 3.0 to 3.5 out of 10 on visual analog scale in
      all 3 groups. The results indicate that patients perceived pain as originating in
      the hip in a high percentage of cases, particularly when proximally coated stems
      were used.

PMID- 10959998
TI  - Total knee arthroplasty after high tibial osteotomy: a medium-term review.
AB  - A total of 50 consecutive knee arthroplasties in 42 patients who had undergone
      previous high tibial osteotomies have been reviewed with a minimum follow-up of 5
      years and compared with 50 age-matched and sex-matched primary total knee
      arthroplasties. There were no significant preoperative differences between the 2
      groups. Surgery in the osteotomy group took on average 23 minutes longer (P <
      .02), and there was a decrease of 80 flexion postoperatively but without an
      associated difference in knee scores. Patellar subluxation was also seen more
      frequently (P < .05). There was no difference in the revision rate at an average
      follow-up of > 6.2 years. Although there are significant technical difficulties
      and subtle clinical differences, the overall outcome remains good to excellent in
      most cases.

PMID- 10959999
TI  - Noncompliance in the inpatient administration of enoxaparin in conjunction with
      epidural or spinal anesthesia.
AB  - Deep venous thrombosis is 1 of the most common postoperative complications
      resulting in significant mortality and morbidity in patients undergoing total hip
      and total knee arthroplasty. Research has shown that the effectiveness and safety
      of low-molecular-weight heparins depend on the timeliness of their
      administration, particularly when used in conjunction with spinal or epidural
      anesthesia, both of which are effective and safe treatment modalities for knee
      and hip arthroplasty. The focus of this study was to examine the compliance with
      current protocols in the administration of enoxaparin (Lovenox) to patients who
      had undergone total joint arthroplasty. We reviewed the perioperative management
      of patients who had a total hip or total knee arthroplasty in which there was the
      combined use of epidural or spinal anesthesia and enoxaparin. Our results show a
      52% (26 of 50) noncompliance rate in the administration of enoxaparin as compared
      with the published protocol for using this treatment modality safely and
      effectively.

PMID- 10960000
TI  - The introduction period of unicompartmental knee arthroplasty is critical: a
      clinical, clinical multicentered, and radiostereometric study of 251 Duracon
      unicompartmental knee arthroplasties.
AB  - One hundred twenty-eight consecutive knees were operated on with the Duracon
      unicompartmental knee arthroplasty. Of 111 knees, followed 3 years (range, 1-6
      years), 109 knees were satisfactory. Two knees were revised because of
      progression of osteoarthritis and inexplicable pain. Radiostereometric analysis
      in 49 knees showed a migration of 0.6 mm after 2 years. The magnitude of
      migration was lower in comparison with published series. In a multicenter study
      comprising 4 other hospitals, there were 8 revisions in 123 operated knees. The
      reasons were loosening, subsidence, or fracture. These revisions were within 1
      year and mostly related to operative technique. Unicompartmental knee
      arthroplasty is a demanding procedure that needs special experience and includes
      a risk of early failures during the introduction of a system.

PMID- 10960001
TI  - A new technique of subtrochanteric shortening in total hip arthroplasty: surgical
      technique and results of 9 cases.
AB  - Total hip arthroplasty for severe chronic proximal femoral migration, most
      commonly seen in congenital dislocation of the hip, has been associated with high
      rates of complications. A new technique of femoral subtrochanteric shortening
      osteotomy with the prosthesis in situ is described. This technique minimizes the
      potential complications, allows for correction of severe femoral neck
      anteversion, and gives excellent rotational stability, while preserving the
      proximal femur for better press-fit cementless fixation. In this series, there
      were 9 cases: 6 women and 2 men with a mean age of 53 years (range, 26-77 years).
      The average follow-up period was 56 months (range, 6-86 months). The mean
      preoperative Harris Hip Score was 31 (range, 20-35), and the mean postoperative
      score was 81 (range, 60-98). At follow-up, all patients reported significant pain
      relief and functional improvement. All osteotomies appeared to be healed on
      radiographs by 12 weeks. There were 3 complications. The first complication was a
      recurrent dislocation resulting from muscle incompetence, which was revised using
      a constrained liner and a 32-mm head with no further dislocations. The second
      complication was a breach of the femoral shaft, which was treated operatively
      using a longer stem. The third complication was a proximal femoral shaft split,
      which was treated by leaving the cerclage wire in situ. This technique should be
      considered in cases of congenital dislocation of the hip and when femoral
      shortening is needed.

PMID- 10960002
TI  - Analysis of the results of the C-Fit uncemented total hip arthroplasty in young
      patients with hydroxyapatite or porous coating of components.
AB  - Young patients at 2 separate centers received a C-Fit uncemented arthroplasty,
      with randomization to porous or hydroxyapatite coating. No difference in survival
      could be found between components that were porous or hydroxyapatite coated, with
      27.5% being revised within 8 years, mainly for aseptic loosening. Acetabular
      augmentation screws or offset acetabular liners similarly did not affect outcome.
      Two of the offset liners had spun within the metal acetabular liners, with early
      failure. Some of the survivors showed poor clinical scores, but there was no
      correlation between clinical score and radiographic evidence of loosening. These
      results are comparable to the poorest reported survival figures in the literature
      for uncemented prostheses. Prosthesis coating could not be shown to affect
      component survival for this prosthesis.

PMID- 10960003
TI  - Histologic and mechanical evaluation of impacted morcellized cancellous
      allografts in rabbits: comparison with hydroxyapatite granules.
AB  - The bioactivity and mechanical properties of morcellized allografts and
      hydroxyapatite (HA) granules were evaluated in a rabbit model. Allografts were
      replaced by viable trabecular structures within 8 weeks. The yield strength and
      stiffness of allografts were within normal cancellous bone levels by 3 weeks and
      were maintained afterward. The amount of newly formed bone around HA granules was
      comparable to that around allografts. The yield strength and stiffness of HA
      granules were significantly higher than those of allografts at 3 and 12 weeks.
      Allografts offer the advantage of being replaced by host-bone without significant
      deterioration in mechanical properties over the course of remodeling. HA granules
      can also be used for a bone substitute given their bioactivity in bone conduction
      and superiority in mechanical properties to allografts.

PMID- 10960004
TI  - CT-generated 3-dimensional models for complex acetabular reconstruction.
AB  - Before undergoing complex acetabular reconstruction, 10 patients who met
      prospectively established criteria for severe acetabular bone deficiency received
      plain radiographs, computed tomography (CT) scans, and CT-generated 3-dimensional
      pelvic models. The radiographs, CT scans, and models each were graded according
      to the American Academy of Orthopaedic Surgery (AAOS) classification for
      acetabular deficiency. The classifications for the radiographs, CT scans, and
      models were then compared with findings at surgery. The models predicted
      acetabular deformity and AAOS classification significantly better than the other
      imaging modalities. The models agreed with the surgical findings in 9 of 10
      cases, compared with 2 of 10 for the CT scans (P = .016) and 4 of 10 for the
      plain radiographs (P = .063). The models closely predicted the available space
      for the hemispheric acetabular shells, based on the size of the last reamer used,
      for the 6 hips reconstructed with standard components. Four patients required
      custom acetabular components; in 2 of those 4, the need for custom components was
      not anticipated by plain radiographs or CT scans. Three-dimensional CT-generated
      acetabular models were found to be useful in preoperative planning of complex
      acetabular reconstructions.

PMID- 10960005
TI  - The effect of particle phagocytosis and metallic wear particles on osteoclast
      formation and bone resorption in vitro.
AB  - Osteoclasts are multinucleated bone-resorbing cells that are formed from
      precursors that circulate in the monocyte fraction. This study has determined the
      effect of phagocytosis of metal particles on osteoclast formation and bone
      resorption in vitro. Human peripheral blood monocytes were cocultured for 21 days
      with osteoblast-like UMR 106 cells, in the presence of 1,25-dihydroxyvitamin D3,
      dexamethasone, and human macophage colony-stimulating factor. Cobalt-chrome alloy
      (CoCr), stainless steel (316L-SS), titanium alloy (TiAlV), and commercially pure
      titanium (cpTi) particles (size range, 0.5-3.0 microm) and 1.0-microm latex
      particles were added to the cocultures as a single dose at the beginning of each
      experiment. All 5 types of particles were readily phagocytosed by the monocytes.
      After 4 days' exposure to high concentrations of all the metal particles, some
      cell death was found in the cocultures. After 14 days, a reduction in the number
      of CD14+ cells was seen in cocultures exposed to high concentrations of metal
      particles, particularly CoCr and 316L-SS particles. Phagocytosis of latex
      particles by osteoclast precursors did not affect the ability of these cells to
      undergo osteoclast differentiation. In contrast, exposure to metal wear particle
      preparations caused a dose-dependent reduction in the number of vitronectin
      receptor-positive osteoclastic cells formed and a dose-dependent reduction in the
      bone resorption produced by these cells. This decrease in resorption was greater
      after exposure to CoCr and 316L-SS particles compared with TiAlV and cpTi
      particles. This in vitro cell culture system may provide a useful model to
      compare the effect of different prosthetic materials on human osteoclast
      formation and bone resorption.

PMID- 10960006
TI  - Effect of mixing technique on the properties of acrylic bone-cement: a comparison
      of syringe and bowl mixing systems.
AB  - Syringe mixing systems have been introduced, but few data exist regarding the
      mechanical performance of cement they produce. We compared the properties of
      polymethyl methacrylate cement produced by these systems with that produced by a
      multiaxial bowl. Mixtures of cement were prepared using the Optivac, Cemvac, and
      Summit syringes and the Summit bowl. The mixtures were cured in molds to create
      casts that were radiographed and analyzed for void content, then cut into strips,
      weighed, measured, and tested to failure in 4-point bending. Syringe-mixed cement
      was of greater density, bending modulus, and bending strength than bowl-mixed
      cement (Mann-Whitney, P < .01) and contained fewer microvoids and macrovoids
      (Mann-Whitney, P < .01). No significant differences between the syringes were
      found for these variables (Kruskall-Wallis, P > .05).

PMID- 10960007
TI  - Warfarin-associated intracapsular hemorrhage causing an acutely painful total hip
      arthroplasty: a rare complication of prolonged anticoagulant therapy.
AB  - Hemorrhage is the most prevalent adverse effect of oral anticoagulant therapy.
      The incidence of bleeding complications is related to the duration and range of
      therapy. A patient on long-term warfarin anticoagulation developed a spontaneous
      intracapsular bleed into a total hip arthroplasty that had been implanted 11
      years before. Joint aspiration allowed early recognition with immediate
      resolution of symptoms. Diagnosis and treatment of this rare complication are
      discussed with a review of the literature.

PMID- 10960008
TI  - False aneurysm of the profunda femoris artery after total hip arthroplasty.
AB  - A false aneurysm of the profunda femoris artery occurred after metal-on-metal
      total hip arthroplasty in 70-year-old woman. At 39 days after the operation, the
      wound suddenly opened, and a large hematoma was discharged. Eleven tornade coils
      were inserted into the base of the false aneurysm, and the bleeding was arrested.
      The prevention and management of this complication are discussed.

PMID- 10960009
TI  - Acute metastatic infection of a revision total hip arthroplasty with oral
      bacteria after noninvasive dental treatment.
AB  - The risk of hematogenous bacterial infection of a total joint prosthesis is
      currently considered to be greatest in the 2 years after arthroplasty or when the
      patient is chronically ill or immunocompromised, for dental treatments that are
      considered invasive, with a higher incidence of bacteremia. We report the case of
      a healthy man who had undergone revision hip arthroplasty 11 months previously
      and who developed acute signs of infection of the hip prosthesis with an oral
      organism 30 hours after supragingival dental cleaning, performed with the
      specific intention to be noninvasive, without antibiotic prophylaxis.

PMID- 10960010
TI  - Calcium and the risk for periodontal disease.
AB  - BACKGROUND: Dietary calcium has long been a candidate to modulate periodontal
      disease. Animal as well as human studies of calcium intake, bone mineral density,
      and tooth loss provide a rationale for hypothesizing that low dietary intake of
      calcium is a risk factor for periodontal disease. METHODS: We evaluated the role
      of dietary calcium intake as a contributing risk factor for periodontal disease
      utilizing the Third National Health and Nutrition Examination Survey (NHANES
      III), which is representative of the U.S. civilian non-institutionalized
      population. Dietary calcium intake was determined from a 24-hour dietary recall.
      The U.S. Department of Agriculture Nutrient Database was used as a source of
      nutrient composition data. Periodontal disease was measured by attachment loss.
      In addition, serum calcium was assessed using venous blood samples. Logistic
      regression analysis was used to examine the association between periodontal
      disease and dietary calcium intake or serum calcium levels after adjusting for
      covariants including age, gender, tobacco consumption, and gingival bleeding.
      RESULTS: The association of lower dietary calcium intake with periodontal disease
      was found for young males and females (20 to 39 years of age), and for older
      males (40 to 59 years of age). The relationship between low dietary calcium
      intake and increased levels of periodontal disease showed an estimated odds ratio
      (OR) of 1.84 (95% CI: 1.36 to 2.48) for young males, 1.99 (95% CI: 1.34 to 2.97)
      for young females, and 1.90 (95% CI: 1.41 to 2.55) for the older group of males.
      These odds ratios were adjusted for gingival bleeding and tobacco consumption.
      The dose response was also seen in females, where there was 54% greater risk of
      periodontal disease for the lowest level of dietary calcium intake (2 to 499 mg)
      and 27% greater risk in females who took moderate levels of dietary calcium (500
      to 799 mg) as compared to those who took 800 mg or more dietary calcium per day.
      A statistically significant association between low total serum calcium and
      periodontal disease was found in younger females aged 20 to 39 with OR = 6.11
      (95% CI: 2.36 to 15.84) but not for males or older females, after adjusting for
      tobacco use, gingival bleeding, and dietary calcium intake. CONCLUSIONS: These
      results suggest that low dietary intake of calcium results in more severe
      periodontal disease. Further studies will be needed to better define the role of
      calcium in periodontal disease and to determine the extent to which calcium
      supplementation will modulate periodontal disease and tooth loss.

PMID- 10960011
TI  - 2-year observation of attachment loss in a rural Chinese population.
AB  - BACKGROUND: Risk indicators for periodontitis seem to vary with study population.
      The purpose of this study was to determine whether risk indicators of additional
      attachment loss differ between generations of Chinese villagers in a rural area
      of China over a 2-year period. METHODS: The study population consisted of 310
      subjects aged 15 to 44. In each subject, 2 quadrants from either the upper or
      lower jaw were randomly selected and 6 sites on each tooth were examined.
      Clinical parameters included plaque scoring system (PSS), calculus index (CI),
      probing depth (PD), attachment level (AL), and sulcus bleeding index (SBI). The
      second examination was done 2 years after the first. RESULTS: In the 15- to 24
      year-old age group, mean PSS, CI, and SBI were significantly higher in subjects
      with additional attachment loss > or =3 mm (AL+) than in those without attachment
      loss (AL-). In the 25- to 34-year-old age group, mean PD was significantly higher
      in AL+ than in AL-, and mean PD and AL were significantly higher in AL+ than in
      AL- in the 35- to 44-year-old age group. Although the number of subjects with AL+
      increased with age, the mean number of sites with AL+ per subject did not differ
      by generation. In addition, smokers tended to exhibit attachment loss more often
      than non-smokers. CONCLUSIONS: The present results suggest that the clinical
      parameters associated with attachment loss differ between generations and that
      gingival inflammation is likely associated with the onset of periodontitis more
      strongly than progression of periodontitis, whereas PD and/or AL are associated
      with the progression of periodontitis.

PMID- 10960012
TI  - Bone mineral density of alveolar bone in rats during pregnancy and lactation.
AB  - BACKGROUND: The present study was designed to investigate the effect of pregnancy
      and lactation on the bone mineral density (BMD) of alveolar bone in rats fed
      diets containing different amounts of calcium (Ca). The effects of different
      levels of Ca intake by the mothers on the BMD of alveolar bone in their pups were
      also examined. METHODS: Ten-week-old female Wistar rats were housed with male
      rats for breeding and were divided into 3 groups fed diets containing 0.9, 0.3,
      and 0.02% Ca, respectively. They were further divided into 2 groups according to
      pregnancy or non-pregnancy. Animals in the pregnant group were raised with their
      own pups for lactation. After the experiment, all animals were sacrificed, their
      mandibles were dissected, and soft x-ray microradiographs were taken to determine
      BMD in the interdental area with an image analyzer. RESULTS: In both groups, BMD
      in alveolar bone decreased based on the amount of Ca in the diet, but the
      magnitude of this decrease was much greater in the pregnant group than in the non
      pregnant group. There was no significant difference in BMD between 2 groups fed a
      0.9% Ca diet. The BMD of alveolar bone in the pups also decreased depending on
      the amount of Ca in the diet. CONCLUSIONS: The above results suggest that
      pregnancy and subsequent lactation could be risk factors for alveolar bone loss,
      especially under conditions of Ca insufficiency or deficiency and that Ca
      insufficiency or deficiency in the mother caused decreases in the BMD of alveolar
      bone in the pups.

PMID- 10960013
TI  - Collagen fibers and inflammatory cells in healthy and diseased human gingival
      tissues: a comparative and quantitative study by immunohistochemistry and
      automated image analysis.
AB  - BACKGROUND: Periodontal disease is histologically characterized by the
      degradation of extracellular matrix components associated with a gingival
      infiltration of inflammatory cell populations. The purpose of this in situ study
      was to quantify inflammatory cell subsets and the area fraction (AA%) occupied by
      collagen fibers in healthy and diseased upper gingival connective tissue in order
      to investigate the association, if any, between collagen loss and inflammatory
      cell infiltrate. METHODS: Paraffin gingival tissue sections from 10 healthy
      controls (C), 9 patients with gingivitis (G), and 10 patients with severe chronic
      periodontitis (P) were immunohistochemically stained by antibodies against CD45,
      CD3, CD8, CD20, CD68, TIA-1, and GrB molecules, and the collagen fibers were
      stained using sirius red F3Ba. The quantitative evaluations of inflammatory cell
      numbers and the AA% occupied by collagen fibers were performed by morphometric
      and automated image analysis. RESULTS: In group P, CD45+, CD20+, CD68+, TIA-1+,
      and GrB+ cell numbers were significantly increased (P<0.05) when compared to both
      C and G groups. The present study revealed significant differences (P <0.01)
      between means of AA% observed in group C (63%), group G (46%), and group P (26%),
      and AA% of group G and group P was inversely correlated with the numbers of TIA
      1+ cells (P<0.01) and GrB+ cells (P<0.01 and P<0.05, respectively). CONCLUSIONS:
      This study showed great differences in the number of the distinct inflammatory
      cell subsets according to the severity of the periodontal disease and suggested
      that activated cytotoxic cells could play a pivotal role in the loss of collagen
      fibers observed during these pathological states. During periodontitis, collagen
      loss was significantly correlated with all inflammatory cell subset numbers.
      Finally, the quantitative evaluation of the area fraction occupied by gingival
      collagen fibers may reflect the clinical severity of the periodontal disease.

PMID- 10960014
TI  - Evaluation of the regenerative effect of a 25% doxycycline-loaded biodegradable
      membrane for guided tissue regeneration.
AB  - BACKGROUND: Biodegradable materials have been successfully utilized for guided
      tissue regeneration (GTR) and local delivery systems (LDS) because they are
      biocompatible, less cytotoxic, and do not require removal. Several studies have
      demonstrated that tetracyclines (TCs), when applied topically, stimulated
      osteogenesis in experimental bone defects. The purpose of this study was to
      evaluate the regenerative effect of a 25% doxycycline-loaded biodegradable GTR
      membrane (Doxy-M) in dogs. METHODS: Doxy-M was made by coating the inner surface
      of a biodegradable membrane (BD-M) with 25% doxycycline. Five male mongrel dogs
      with 20 created osseous defects were enrolled. The plain BD-M was used as the
      control membrane. Either Doxy-M or BD-M was applied in 20 randomly selected
      defects (10 Doxy-M, 10 BD-M) for 12 weeks with the GTR technique. The histometric
      analysis was evaluated with the following parameters: defect height (DH), apical
      extension of junctional epithelium (AEJP), new cementum height (NCH), new bone
      height (NBH), and new bone area (NBA). RESULTS: The Doxy-M-treated defects showed
      more pronounced new bone formation and less crestal bone resorption than the BD-M
      treated defects. There were no statistically significant differences between the
      two groups in DH, AEJP, and NCH. Statistically significantly larger NBH (P <0.05)
      and NBA (P<0.005) were seen in the Doxy-M-treated defects. CONCLUSIONS: The
      results strongly suggest that Doxy-M may have a beneficial effect on osteogenesis
      to favor periodontal regeneration.

PMID- 10960015
TI  - A study of attached and oriented human periodontal ligament cells to
      periodontally diseased cementum and dentin after demineralizing with neutral and
      low pH etching solution.
AB  - BACKGROUND: This study aimed to evaluate quantitatively the migrated, attached,
      and oriented human periodontal ligament cells (HPLC) to periodontally diseased
      cementum and dentin after demineralization with low and neutral pH etching
      solution. METHODS: Human teeth, extracted due to periodontal diseases, were
      scaled and root planed so that cementum remained on one longitudinal half of the
      root and dentin was exposed on the other half. Forty root slices of 200 microm
      thickness, obtained from the mid-third of these roots, were divided into four
      groups: group 1, demineralized with a saturated solution of citric acid (pH
      1.20); group 2, with 24% EDTA (pH 7.04); group 3, with tetracycline HCl 100 mg/ml
      (pH 2.00); and group 4, only scaled and root planed (control). Root slices were
      placed over the confluent HPLC in 35 mm culture dishes and incubated. Phase
      contrast microscopic photographs of attached and oriented refractile HPLC to root
      surfaces were taken at days 1, 3, and 7. Quantitative analysis of attached and
      oriented HPLC from these photographs was done using special software. RESULTS:
      The results showed no significant difference in the attachment and orientation
      index of HPLC to cementum compared to dentin in any method of demineralization at
      each time point (P >0.05), although there was a significantly higher cell
      attachment and orientation index to demineralized dentin with EDTA and citric
      acid than to non-etched dentin and to all 3 demineralized cementum surfaces
      compared to non-etched cementum (P<0.05). CONCLUSIONS: EDTA and citric acid
      demineralization may enhance HPLC attachment and orientation to the root surface,
      and it is not always necessary to remove excessive cementum when the
      demineralizing procedure is used.

PMID- 10960016
TI  - Biological effects of cementum and bone extracts on human periodontal
      fibroblasts.
AB  - BACKGROUND: Non-collagenous proteins of mineralized tissues play important roles
      in bone induction during mineralization and in regulating the activity of many
      types of mesenchymal cells. This study was conducted to determine the effects of
      acetic acid extracts of bone and cementum on alkaline phosphatase (ALPase)
      activity and in vitro mineralization of cultured human periodontal fibroblasts
      (hPF). METHODS: Alveolar bone and cementum obtained from clinically healthy
      subjects were extracted by a solution containing 0.5 M acetic acid and enzyme
      inhibitors. Osteoblastic phenotypes of hPF were assayed by ALPase activity, gene
      expression of bone marker proteins, and the ability to produce in vitro
      mineralization in culture media containing 50 microg/ml ascorbic acid, 10 mM
      sodium beta-glycerophosphate, and 10(-7) M dexamethasone. The effects of cementum
      and bone extracts on the expression of osteoblastic phenotypes in hPF were also
      determined. RESULTS: Many protein components, varying in molecular weight from 10
      to 14 to 120 kDa, were detectable in 10% SDS-PAGE of both cementum and alveolar
      bone extracts. The hPF cells were found to exhibit a moderate ALPase activity
      when compared with rat osteosarcoma (ROS) 17/2.8 cells under the same
      experimental conditions. Gene expression for ALPase, osteocalcin bone
      sialoprotein, osteopontin, and BMP-7 at mRNA message was detected by RT-PCR in
      hPF and ROS 17/2.8 cells. The confluent hPF and ROS 17/2.8 cells showed evidence
      of calcium deposition in the extracellular milieu at 30 and 15 to 30 days'
      cultures, respectively, under a mineralization medium. The hPF appeared to form
      mineralized foci with morphological characteristics different from the
      mineralized nodules produced by ROS 17/2.8 cells. The addition of low
      concentrations (5 microg/ml) of either cementum or bone extract produced an
      increase in the size and number of mineralization spots, as well as greater
      ALPase activity in both hPF and ROS 17/2.8 cultures during the observation
      periods. CONCLUSIONS: These results suggest that hPF possess certain mineralizing
      phenotypes, and that acetic acid extracts of bone and cementum contain components
      capable of stimulating osteogenic differentiation of hPF.

PMID- 10960017
TI  - A comparison between enamel matrix proteins used alone or in combination with
      bovine porous bone mineral in the treatment of intrabony periodontal defects in
      humans.
AB  - BACKGROUND: It has been shown that clinical improvement of intrabony periodontal
      defects can be achieved with the use of enamel matrix proteins (EMPs) or by
      grafting with bovine porous bone mineral (BPBM). There is no report on the
      potential synergistic effect of EMPs and BPBM in periodontal regenerative
      therapy. The purpose of this study was to compare the clinical effectiveness of
      EMPs used alone or in combination with BPBM in the treatment of periodontal
      intrabony defects in humans. METHODS: Twenty-one paired intrabony defects were
      surgically treated using a split-mouth design. Intrabony defects were treated
      either with enamel matrix proteins (EMP group) or with enamel matrix proteins
      combined with bovine porous bone mineral (EMP/BPBM group). Re-entry surgeries
      were performed at 6 months. RESULTS: Preoperative probing depths, attachment
      levels, and transoperative bone measurements were similar for the EMP and
      EMP/BPBM groups. Postsurgical measurements taken at 6 months revealed a
      significantly greater reduction in probing depth in the EMP/BPBM group (3.43 +/-
      1.32 mm on buccal sites and 3.36 +/- 1.35 mm on lingual sites) when compared to
      the EMP group (1.91 +/- 1.42 mm on buccal sites and 1.85 +/- 1.38 mm on lingual
      sites). The EMP/BPBM group also presented with significantly more attachment gain
      (3.13 +/- 1.41 mm on buccal sites and 3.11 +/- 1.39 mm on lingual sites) than the
      EMP group (1.72 +/- 1.33 mm on buccal sites and 1.75 +/- 1.37 mm on lingual
      sites). Surgical re-entry of the treated defects revealed a significantly greater
      amount of defect fill in favor of the EMP/BPBM group (3.82 +/- 1.43 mm on buccal
      sites and 3.74 +/- 1.38 mm on lingual sites) as compared to the EMP group (1.33
      +/1.17 mm on buccal sites and 1.41 +/- 1.19 mm on lingual sites). CONCLUSIONS:
      The results of this study indicate that BPBM has the ability to augment the
      effects of EMPs in reducing probing depth, improving clinical attachment levels,
      and promoting defect fill when compared to presurgical levels.

PMID- 10960018
TI  - Mast cells are not involved in the development of cyclosporin A-induced gingival
      hyperplasia: a study with mast cell-deficient mice.
AB  - BACKGROUND: A previous study suggested that mast cells (MC) are involved in the
      development of cyclosporin A-induced gingival hyperplasia, since an increased
      number of MC were observed in the tissue sections of enlarged gingiva. To
      determine the role of MC in gingival hyperplasia, an MC-deficient mouse model was
      used in the current study. METHODS: MC-deficient mice (WBB6F1xW/Wv) and their
      littermates (+/+) were fed sucrose-containing diets supplemented with or without
      varying concentrations (300, 400, 500, 600 mg) of cyclosporin A/kg of diet. After
      30 days, the mice were sacrificed and the degree of gingival hyperplasia was
      evaluated by the appearance of the gingiva. Tissue MC were stained with toluidine
      blue to confirm the presence or absence of MC in the enlarged gingiva. RESULTS:
      Both W/Wv and +/+ mice, when fed with 600 mg cyclosporin A/kg diet for 30 days,
      exhibited a similar degree of gingival hyperplasia, while other test mice or
      control mice did not. Toluidine blue staining of the tissue sections confirmed
      the presence of MC in the enlarged gingiva of the +/+ mice, but not the W/Wv
      mice. CONCLUSIONS: These results indicate that mast cells are not necessary in
      the development of cyclosporin A-induced gingival hyperplasia, and that the
      increased number of MC observed in the enlarged gingiva may be a secondary effect
      of gingival hyperplasia. We also conclude that a study of mice lacking certain
      molecules or cells would be quite useful in determining the molecules or cell
      types responsible for the pathogenesis of drug-induced gingival hyperplasia.

PMID- 10960019
TI  - Neutrophils die in the gingival crevice, periodontal pocket, and oral cavity by
      necrosis and not apoptosis.
AB  - BACKGROUND: Neutrophils play important roles in the homeostasis of periodontal
      tissues. However, remarkably little is known about how these cells live and die
      in the gingival crevice and periodontal pocket. We have examined whether
      subgingival neutrophils die by necrosis or apoptosis and have begun to study the
      mechanisms controlling the functional lifespan of these cells. METHODS:
      Neutrophils collected from clinically healthy gingival crevices, periodontal
      pockets, and the oral cavity (saliva) were examined with Hoechst dye 33342,
      propidium iodide/eithidium bromide, and FITC-annexin V to identify live, dead,
      and apoptotic cells. Blood neutrophils were cultured for 17 to 20 hours in the
      presence or absence of gingival crevice washings (GC-w) to study the effect of GC
      w on neutrophil apoptosis. In addition, endotoxin was removed from GC-w by
      affinity resin to investigate the contribution of LPS to the inhibitory effect of
      GC-w on blood neutrophils. RESULTS: The percentage of dead neutrophils in all
      subgingival sites and in all oral samples far exceeded the percentage of
      apoptotic neutrophils. In all 3 locations, approximately 30% of neutrophils were
      dead, whereas less than 1% of neutrophils were apoptotic. We conclude that the
      majority of neutrophils which lose their viability within gingival crevices,
      periodontal pockets and the oral cavity die by necrosis and not by apoptosis.
      Washings obtained from clinically healthy gingival crevices (GC-w) variably, but
      significantly, delayed apoptosis of peripheral blood neutrophils (mean
      suppression 45.7% +/- SD 22.3). Removal of endotoxin from GC-w significantly
      reduced this inhibitory effect. CONCLUSIONS: Our findings provide insights into
      the mechanisms of neutrophil death and the control of the functional lifespan of
      neutrophils in gingival crevices and periodontal pockets and therefore into the
      pathogenesis of periodontal diseases.

PMID- 10960020
TI  - The influence of genetic variation on the splenic T cell cytokine and specific
      serum antibody responses to Porphyromonas gingivalis in mice.
AB  - BACKGROUND: T cell cytokine profiles in the spleens and anti-Porphyromonas
      gingivalis antibodies in the sera of P. gingivalis-immunized BALB/c (H-2d),
      CBA/CaH (H-2k), C57BL6 (H-2b), and DBA/2J (H-2d, C5 deficient) mice were
      examined. METHODS: Mice were immunized either by intraperitoneal injections of P.
      gingivalis outer membrane antigens and Freund's incomplete adjuvant weekly for 3
      weeks or sham-immunized with PBS and adjuvant, followed by subcutaneous challenge
      with live organisms 1 week after the final immunization. Spleens were excised and
      blood samples collected by heart puncture at 0 and 7 days after challenge.
      Splenic CD4 and CD8 cells were stained for intracytoplasmic interleukin (IL)-4,
      interferon (IF)-gamma, and IL-10 and levels of anti-P. gingivalis antibodies in
      the serum samples determined by ELISA. RESULTS: Lesion sizes in immunized BALB/c
      mice remained stable for the 7-day experimental period. Immunized CBA/CaH and
      C57BL6 mice exhibited large lesions at day 1 reducing by day 7 particularly in
      the latter strain. Lesions in immunized DBA/2J mice were still larger than the
      other strains at day 7. With the exception of DBA/2J mice, sham-immunized mice
      demonstrated lesions which did not show signs of healing by day 7. T cell
      cytokine responses in sham-immunized mice at day 0 were low, increasing to a
      variable degree by day 7 after challenge in the 4 strains. Immunized BALB/c mice
      demonstrated intermediate T cell responses while generally exhibiting a stronger
      IFN-gamma response than IL-4 or IL-10. Immunized CBA/CaH and C57BL6 mice showed
      weak T cell cytokine responses while immunized DBA/2J displayed the strongest T
      cell responses particularly in regard to IL-4 positive cells. Sham-immunized mice
      had low levels of serum anti-P. gingivalis antibody levels at day 0 with levels
      increasing significantly by day 7 after challenge. Antibody levels in immunized
      mice seemed to correlate with lesion sizes. Immunized C57BL6 mice had the highest
      antibody levels followed by CBA/CaH, BALB/c with DBA/2J exhibiting low levels.
      The T cell and B cell antibody responses in each strain appeared to exhibit an
      inverse relationship. CONCLUSIONS: This study has shown that genetic differences
      at the level of H-2 haplotype induce variations in the local and T and B cell
      responses to P. gingivalis antigens. The responses of DBA/2J mice which have the
      same haplotype as BALB/c mice suggest that factors other than H-2 haplotype such
      as the C5 deficiency may influence this immune response. The significance of the
      specific antibody and T cell responses and of their inverse relationship to
      susceptibility to periodontal disease remains to be determined.

PMID- 10960021
TI  - An in vitro screening model to evaluate root conditioning protocols for
      periodontal regenerative procedures.
AB  - BACKGROUND: Preclinical studies have shown that the condition of the root surface
      may play a decisive role for outcome of wound healing between a mucogingival flap
      and a denuded root surface. Root surface demineralization has been shown to
      promote the establishment of a new connective tissue attachment. Conversely, root
      conditioning with extracellular matrix proteins or fluorides has produced
      outcomes characterized by a long junctional epithelium. Collectively, present
      evidence suggests that early events in the healing sequel; i.e., the adsorption
      and adhesion of blood elements to the root surface are critical for outcomes of
      wound healing between a mucogingival flap and a denuded root surface. Ultimately
      understanding and control of these events are vital for successful design and
      execution of periodontal regenerative protocols, particularly those involving
      root conditioning. Consequently, the objective of this study was to develop a
      screening model for immediate evaluation of the influence of root conditioning
      protocols on the adsorption and adhesion of blood to dentin surfaces. METHODS:
      Planed and citric acid-treated human dentin surfaces were exposed to fresh blood
      allowed to clot and were then rinsed before scanning electron microscopy
      evaluation. RESULTS: Citric acid treated planed dentin surfaces presented a thick
      network of fibrin directly attaching to the dentin surface entrapping cellular
      elements, mainly erythrocytes. In contrast, untreated, planed dentin exhibited an
      amorphous appearance with sparse strands of adsorbed fibrous proteins and few
      adherent erythrocytes. CONCLUSIONS: This in vitro screening model may effectively
      distinguish dentin surfaces with potential for enhanced adsorption and adhesion
      of blood elements. Periodontal regenerative protocols involving root conditioning
      unsuccessful in maintaining the experimentally imposed fibrin clot in this model
      may have lesser clinical significance than those that do.

PMID- 10960023
TI  - Aspartate aminotransferase activity in crevicular fluid from dental implants.
AB  - BACKGROUND: Aspartate aminotransferase (AST) is an enzyme normally confined to
      the cytoplasm of cells, but released to the extracellular environment upon cell
      death. Its levels are associated with the severity of experimental gingivitis and
      the loss of periodontal attachment. The aim of the present study was to
      investigate the presence and activity levels of AST in peri-implant crevicular
      fluid (PCF) from healthy and diseased endosseous implants in order to assess if
      AST in PCF can be further studied as a possible objective diagnostic aid in oral
      implantology. METHODS: Eighty-one fixtures from 81 systemically healthy subjects
      were divided into 3 groups, 27 healthy implants (HI), 27 implants with mucositis
      (MI) and 27 implants affected by peri-implantitis (PI) according to well-defined
      clinical and radiographic criteria. PCF was collected by the insertion of a #40
      standardized endodontic paper point to the base of the crevice or pocket for 30
      seconds. AST activity was determined spectrophotometrically at 25 degrees C. The
      results were expressed as AST Units/ml in PCF. RESULTS: An AST activity was
      detected in each sample from HI, MI and PI. The mean AST activity in HI was 0.26
      +/- 0.16 U/ml; in MI, 0.38 +/- 0.27 U/ml; in PI, 0.62 +/- 0.29 U/ml. ANOVA showed
      that the difference among HI, MI, and PI was statistically significant at P <0.01
      level. Post-hoc tests demonstrated that a significant difference in AST activity
      existed between HI/PI (t = 5.14; P<0.01) and MI/PI (t = 3.09; P<0.01). No
      statistically significant difference was found between HI/MI (t = 1.07; P >0.1)
      AST activity was significantly (P <0.01) associated with probing depth (r =
      0.55), the amount of bone loss (r = 0.60) and bleeding on probing (r = 0.67).
      When the threshold for a positive AST test was set > or =0.4 U/ml, a sensitivity
      = 0.81 and a specificity = 0.74 were found in the detection of peri-implantitis;
      the positive predictive value was 61% and the negative predictive value was 88%.
      CONCLUSIONS: Within the limits of this study, our results may suggest that PCF
      analysis could be further investigated in longitudinal studies as a suitable
      diagnostic strategy in the evaluation of dental implants.

PMID- 10960022
TI  - Fusobacterium nucleatum involvement in adult periodontitis and possible
      modification of strain classification.
AB  - BACKGROUND: This investigation was designed to evaluate the involvement of
      Fusobacterium nucleatum clinical strains in adult periodontitis by subspecies and
      expression of hemagglutination activity. METHODS: Forty-nine Fusobacterium
      strains were isolated from 40 sites in 40 subjects presenting with adult
      periodontitis. F. nucleatum subspecies identification was based on the
      electrophoretic migration of glutamate dehydrogenase and 2-oxoglutarate
      reductase. Hemagglutination activity and inhibition by galactose were tested on
      sheep erythrocytes. RESULTS: The 49 isolates belonged to the F. nucleatum species
      with a predominance of the nucleatum (34.7%) followed by the vincentii (26.5%)
      subspecies. In parallel, 71% of the strains belonging to the nucleatum subspecies
      were preferentially associated with Porphyromonas gingivalis. Prevotella
      intermedia/nigrescens detection was essentially correlated with identification of
      Fusobacterium nucleatum subspecies vincentii. No correlation was established
      between any particular subspecies and the pathogenicity factors tested
      (hemagglutination and production of short-chain fatty acids). On the other hand,
      significant predominance (65%, P= 0.017) of strongly hemagglutinating strains
      (titre > or =8 U) was observed in the sites where Porphyromonas gingivalis,
      Prevotella intermedia/nigrescens and/or Campylobacter rectus were not detected.
      These strains also showed higher butyric acid production. CONCLUSION: The
      importance of the adherence factors for Fusobacterium nucleatum strains and their
      multimodal aspect may indicate a higher pathogenicity or a higher involvement of
      certain strains and could lead to a classification of these strains, which is
      more closely related to their implication in the development of periodontal
      disease.

PMID- 10960024
TI  - Effects of bisphosphonate on matrix metalloproteinase enzymes in human
      periodontal ligament cells.
AB  - BACKGROUND: The host response is a critical component in the pathogenesis of
      periodontitis. In fact, the clinical benefits associated with regulating the host
      response have been demonstrated in studies using several different classes of
      drugs. Biophosphates are one host-modulating class of drugs that has demonstrated
      this ability. These drugs are clinically effective at reducing bone resorption
      and have shown the ability to inhibit host degradative enzymes, specifically the
      matrix metalloproteinases (MMPs). Therefore, the purpose of this study was to
      investigate the regulatory effects of a bisphosphonate, tiludronate, on MMP
      levels and activity in human periodontal cells. METHODS: MMP-1 and MMP-3 were
      assessed in cultured human periodontal ligament cells treated with a
      bisphosphonate, tiludronate. Reverse transcription-polymerase chain reaction was
      used to identify mRNA levels for both enzymes, and also for tissue inhibitors
      (TIMP-1). Enzyme immunoassay (EIA) and immunocytochemistry were used to assess
      MMP proteins in these cell cultures. Enzyme activity was assessed using FITC
      conjugated substrates and quantitated using spectrophotofluorometry. RESULTS:
      Tiludronate significantly inhibited both MMP-1 and MMP-3 activity in a
      concentration-dependent manner. A maximal reduction in activity of 35% was
      achieved for each of the enzymes at a 10(-4) M concentration. Tiludronate did not
      have a significant effect on the mRNA levels for MMP-1, MMP-3, or TIMP-1.
      Similarly, there were no effects noted for either MMP-1 or MMP-3 on the protein
      level. CONCLUSIONS: This study demonstrates an inhibitory effect of tiludronate
      on the activity of both MMP-1 and MMP-3. These effects appear to occur without
      altering either mRNA or protein levels for these enzymes, supporting a possible
      mechanism of action that involves the ability of bisphosphonates to chelate
      cations from the MMPs. Furthermore, these results support the continued
      investigation of these drugs as potential therapeutic agents in periodontal
      disease.

PMID- 10960026
TI  - Peripheral ameloblastoma: a report of 2 cases.
AB  - Peripheral ameloblastoma (PA) is a rare odontogenic tumor most common in elderly
      patients. They are usually solitary; red or pink granular, nodular, or papillary
      lesions; up to 1.5 cm in diameter; and either not resorb bone or produce a
      shallow erosion. Peripheral ameloblastoma should be included in the differential
      diagnosis of soft tissue lumps on the gingiva or edentulous alveolus.

PMID- 10960025
TI  - Induction of experimental periodontitis in mice with Porphyromonas gingivalis
      adhered ligatures.
AB  - BACKGROUND: Little information is available on the colonization of
      periodontopathic bacteria and alveolar bone loss in a mouse system, because of
      the difficulty in establishing bacteria in the oral cavity. The aim of this study
      was to establish experimental periodontitis in mice by applying a Porphyromonas
      gingivalis-adhered ligature onto the molars. METHODS: Specific pathogen-free
      C3H/HeN mice were divided into 3 groups: 80 infected, 80 sham-infected, and 48
      non-treated control mice. Sterile silk ligatures were preincubated with and
      without P. gingivalis 381 in vitro and then physically tied on the right
      maxillary first molar of infected and sham-infected mice, respectively. Ten mice
      from the infected and sham-infected groups and 6 from the control group were
      sacrificed at 2-week intervals for up to 15 weeks after infection. RESULTS:
      Plaque samples were collected at the time of sacrifice and alveolar bone loss was
      examined. The results indicated that P. gingivalis was recovered from the plaque
      samples in 95% of the infected mice after 1 week and then gradually dropped to
      58% after 15 weeks of infection, whereas P. gingivalis was not isolated in either
      sham-infected or control mice throughout the experimental period. The infected
      mice showed significant P. gingivalis-induced bone loss at the sites where the
      ligature was tied weeks 13 to 15. A linear regression analysis revealed a
      significant positive correlation between the number of P. gingivalis recovered
      and alveolar bone loss at 15 weeks after infection (P <0.01). CONCLUSIONS: The
      use of a P. gingivalis-adhered ligature supported a long-lasting infection of P.
      gingivalis in mice, resulting in P. gingivalis-induced alveolar bone breakdown.

PMID- 10960027
TI  - Peripheral clear cell calcifying epithelial odontogenic tumor. Report of a case.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is an uncommon, locally aggressive
      odontogenic tumor representing less than 1% of all odontogenic tumors. Clear
      cells have been described in CEOT, ameloblastomas, calcifying odontogenic cysts,
      lateral periodontal, and gingival cysts. It is not yet clear if the clear cell
      variants of the odontogenic tumors have a different biologic behavior, even if it
      seems that these tumors are more aggressive with an higher recurrence rate. The
      authors present a case of a peripheral clear cell CEOT (CCCEOT). It is a rare
      lesion with only 9 cases reported in the literature. The lesion was removed by
      excision and no recurrence was found after a 4-year follow-up.

PMID- 10960028
TI  - Severe gingival recession in trisomy 18 primary dentition. A clinicopathologic
      case report of self-inflicted injury associated with mental retardation.
AB  - This clinicopathologic case report documents severe gingival recession in the
      primary dentition of a trisomy 18 patient. Primary molar and canine teeth
      exhibited recession extending beyond the midpoint of the buccal aspect of the
      root, occasionally reaching the root apex. Radiographic examination revealed
      taurodontism in both primary and permanent teeth. Clinical and histopathologic
      findings, along with case history, eliminated the possibility of prepubertal
      periodontitis and suggested a diagnosis of self-inflicted injury associated with
      mental retardation. Histologic examination of the primary teeth revealed normal
      cementum and dentin structure. Taurodontism, histologic structure of the
      dentition, and severe attachment loss in the primary dentition have not been
      described previously in trisomy 18.

PMID- 10960029
TI  - The use of hydroxyapatite bone cement for sinus floor augmentation with
      simultaneous implant placement in the atrophic maxilla. A report of 10 cases.
AB  - BACKGROUND: Dental implant placement associated with sinus floor augmentation in
      a severely atrophic maxilla can be performed in a 1- or 2-stage surgical
      procedure, depending on the height of the residual alveolar bone. A minimum of 4
      to 5 mm is recommended for a 1-stage procedure. METHODS: This clinical study
      describes the use of hydroxyapatite (HA) bone cement to stabilize HA-coated
      cylindrical implants placed simultaneously during sinus augmentation in 100
      patients where insufficient bone volume did not allow primary implant stability.
      A total of 26 HA-coated dental implants were inserted in 100 grafted sinuses of
      10 patients. RESULTS: None of the cases presented any difficulty in achieving
      initial stabilization and parallelism. No clinical complications of the sinuses
      were evident. Prior to exposure, radiographic evaluation revealed the implants
      embedded in a densely homogeneous radiopaque mass. At second-stage surgery, there
      was no clinical evidence of crestal bone loss around the implants. All implants
      were clinically osseointegrated. All patients received fixed implant-supported
      prostheses. Mean follow-up was 18 months (range 12 to 24 months). CONCLUSIONS:
      According to this preliminary study, the hydroxyapatite bone cement appears to
      hold great promise as a grafting alloplastic material for sinus floor
      augmentations. Its main advantage is its ability to provide initial stability
      required for osseointegration and proper implant location and parallelism.
      Further clinical and histological studies are required before it can be
      recommended for routine use in sinus lift procedures.

PMID- 10960030
TI  - Pyrazole related nucleosides 5. Synthesis and biological activity of 2'-deoxy
      2',3'-dideoxy- and acyclo-analogues of 4-iodo-1-beta-D-ribofuranosyl-3
      carboxymethyl pyrazole (IPCAR).
AB  - Continuing our studies on the structure-activity relationships (SAR) of 4-iodo-1
      beta-D-ribofuranosyl-3-carboxymethyl pyrazole (IPCAR), the ribofuranosyl moiety
      has been substituted with acyclic chains, namely 1-[(2-hydroxyethoxy)methyl]- and
      1-[(1,3-dihydroxy-2-propoxy)methyl]-pyrazole derivatives (4, 5 and 8, 9
      respectively), with the 2'-deoxy-beta-D-ribofuranosyl group (12 and 13) and
      finally with the 2',3'-dideoxy-D-glycero-pentofuranosyl-moiety (16 and 17). None
      of the new compounds display any interesting biological activity.

PMID- 10960031
TI  - Nucleic acid components and their analogues: new synthesis of bicyclic
      thiopyrimidine nucleosides.
AB  - A novel synthesis of condensed bicyclic thiopyrimidine glycosides utilising 1H
      cyclopentapyrimidine-2(3H)-thiones and alpha-bromoglucose or alpha-bromogalactose
      tetraacetate as starting components is described.

PMID- 10960032
TI  - Synthesis of 3'-O2-(azaheterocycle)-thymidines.
AB  - The synthesis of 3'-O2-(azaheterocycle)-thymidines is presented from 1-thia-3-aza
      1,3-butadiene precursors (N-thioacylamidines). A variety of heterocycles is
      accessible using the dienic, the electrophilic or the nucleophilic reactivity of
      these thia-azabutadiene systems. 3'-O2-(azaheterocycle)-thymidine analogues are
      regarded as potential substrates to interfere with the DNA-polymerization
      process.

PMID- 10960033
TI  - Replacement of the phosphodiester bond between U4 and G5 in the U-turn of a
      chemically modified hammerhead ribozyme by an amide bond.
AB  - The phosphodiester bond between U4 and G5 in the U-turn of a chemically modified
      hammerhead ribozyme was substituted by an amide backbone without compromising the
      ribozyme's cleavage activity. Furthermore, the modified ribozyme proved to be
      completely stable against endonucleolytic digestion at this position.

PMID- 10960034
TI  - Synthesis of 3'-trifluoromethyl nucleosides as potential antiviral agents.
AB  - 1,2-Di-O-acetyl-3-deoxy-3-trifluoromethyl-5-O-benzoyl-beta-D-ribofuranos e was
      synthesized from the precursor keto sugar by the use of Ruppert's reagent
      (CF3SiMe3) as the source of a nucleophilic trifluoromethyl group. Coupling of
      this trifluoromethyl sugar with nucleobases and elaboration gave novel deoxy and
      dideoxynucleosides. A single crystal X-ray analysis confirmed the structure and
      stereochemistry. The deoxynucleosides were converted through an elimination
      reaction to their dideoxydidehydro derivatives.

PMID- 10960035
TI  - Highly stereoselective synthesis and biological properties of nucleoside
      analogues bearing a spiro inserted oxirane ring.
AB  - Starting from 2',5'-di-O-TBDMS-3'-ketouridine 1 or its thymine analogue 2, both
      xylo (3-10) and ribo (20) epimers of a series of 3"-substituted 3'
      spironucleosides have been obtained in good yields and with a total
      stereoselectivity. Most new compounds were moderately cytotoxic with in some
      cases slightly selective antiproliferative activities. None of these compounds
      was active against HIV, but some other antiviral activities against HSV-2, CMV,
      EBV, or VZV, in the micromolar range, were noted in specific cases.

PMID- 10960036
TI  - Metabolism of O6-propyl and N6-propyl-carbovir in CEM cells.
AB  - The metabolism of O6-propyl-carbovir and N6-propyl-carbovir, two selective
      inhibitors of HIV replication, has been evaluated in CEM cells. Both compounds
      were phosphorylated in intact cells to carbovir-5'-triphosphate. The metabolism
      of these two agents was inhibited by deoxycoformycin and mycophenolic acid, but
      not erythro-9-(2-hydroxy-3-nonyl)adenine. No evidence of the 5'-triphosphate of
      either compound was detected in CEM cells.

PMID- 10960038
TI  - New purine derivatives for efficient preparation of nucleoside analogs via
      alkylation.
AB  - New diazabicycloundecenium and phosphazenium derivatives of purines are
      introduced for mild and efficient preparation of nucleoside analogs via in situ
      alkylation. Diazabicycloundecenium salts of purines were obtained directly as a
      result of an unusual reaction between two corresponding amino compounds.

PMID- 10960037
TI  - The synthesis of cyclonucleotides with fixed glycosidic bond linkages as putative
      agonists for P2-purinergic receptors.
AB  - Cyclonucleotides with fixed glycosidic bond linkages were investigated as
      possible ligands for purinoceptors in PC12 cells. P2Y2-purinoceptors were not
      activated by the ATP analogue, 8,2'-thioanhydroadenosine-5'-triphosphate (4) and
      only weakly by the UTP analogue, 2,2' -anhydrouridine-5'-triphosphate (6).
      However, both analogues were agonists for P2X2-purinoceptors although the
      potencies were approximately 30-fold less than that of the parent nucleotides.

PMID- 10960039
TI  - Preparation, hydrolysis and intramolecular transesterification of 3'-deoxy-3'
      thioinosine 3'-S-dimethylphosphorothiolate.
AB  - The hydrolytic reactions of the dimethyl ester of 3'-deoxy-3'-thioinosine 3'-S
      phosphorothiolate have been followed over a wide aciditiy range by HPLC. At pH >
      3, only hydroxide ion catalyzed isomerization to the 2'-dimethylphosphate takes
      place, whereas under more acidic conditions hydrolysis to the 2'
      monomethylphosphate and 3'-S-monomethylphosphorothiolate competes. The latter is
      the only product accumulating in very acidic solutions (1 M hydrochloric acid).
      Mechanisms of the reactions are discussed.

PMID- 10960040
TI  - Synthesis of 9-(2-deoxy-beta-D-ribofuranosyl)purine-2-thione.
AB  - A synthesis of 9-(2-deoxy-beta-D-ribofuranosyl)purine-2-thione was performed by
      desulfurization of 2'-deoxy-6-thioguanine to give 2-amino-9-(2-deoxy-beta-D
      ribofuranosyl)purine, diazotization with chloride replacement to give 2-chloro-9
      (2-deoxy-beta-D-ribofuranosyl)purine, and the replacement of chloride with sulfur
      using thiolacetic acid and deacetylation.

PMID- 10960041
TI  - Nuclear gene LCAT supports rodent monophyly.

PMID- 10960042
TI  - Disorder of movement preparation in dystonia.

PMID- 10960043
TI  - The pedunculopontine nucleus and Parkinson's disease.
AB  - Akinesia and gait disturbances are particularly incapacitating for patients with
      Parkinson's disease. The anatomical and physiological substrates for these
      disturbances are poorly understood. The pedunculopontine nucleus (PPN) is thought
      to be involved in the initiation and modulation of gait and other stereotyped
      movements, because electrical stimulation and the application of neuroactive
      substances in the PPN can elicit locomotor activity in experimental animals.
      Glutamatergic neurones of the PPNd (pars dissipatus) are thought to be important
      regulators of the basal ganglia and spinal cord. The other component of the PPN,
      the cholinergic pars compacta (PPNc), is a principal component in a feedback loop
      from the spinal cord and limbic system back into the basal ganglia and thalamus.
      Electrophysiological studies suggest that 'bursting' glutamatergic PPNd neurones
      are related to the initiation of programmed movements while non-bursting
      cholinergic PPNc neurones are related to the maintenance of steady-state
      locomotion. Furthermore, since patients with Parkinson's disease have significant
      loss of PPN neurones and experimental lesions in the PPN of normal monkeys result
      in akinesia, the degeneration of PPN neurones or their dysfunction may be
      important in the pathophysiology of locomotor and postural disturbances of
      parkinsonism. The goal of this review is (i) to highlight the anatomical
      connections and physiological attributes of the PPN, (ii) to discuss how the
      function of these connections may be altered in the parkinsonian state, and (iii)
      to speculate how present and potential future therapy directed to the PPN might
      improve akinesia and gait difficulties in parkinsonian patients.

PMID- 10960044
TI  - Genetics and ischaemic stroke.
AB  - Ischaemic stroke can be caused by a number of monogenic disorders, and in such
      cases stroke is frequently part of a multisystem disorder. Cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leucoencephalopathy
      (CADASIL), due to mutations in the NOTCH: 3 gene, is increasingly appreciated as
      a cause of familial subcortical stroke. The genetics and phenotypes of monogenic
      stroke are covered in this review. However, the majority of cases of ischaemic
      stroke are multifactorial in aetiology. Strong evidence from epidemiological and
      animal studies has implicated genetic influences in the pathogenesis of
      multifactorial ischaemic stroke, but the identification of individual causative
      mutations remains problematic; this is in part limited by the number of
      approaches currently available. In addition, genetic influences are likely to be
      polygenic, and ischaemic stroke itself consists of a number of different
      phenotypes which may each have different genetic profiles. Almost all human
      studies to date have employed a candidate gene approach. Associations with
      polymorphisms in a variety of candidate genes have been investigated, including
      haemostatic genes, genes controlling homocysteine metabolism, the angiotensin
      converting enzyme gene, and the endothelial nitric oxide synthase gene. The
      results of these studies, and the advantages and limitations of the candidate
      gene approach, are presented. The recent biological revolution, spurred by the
      human genome project, promises the advent of novel technologies supported by
      bioinformatics resources that will transform the study of polygenic disorders
      such as stroke. Their potential application to polygenic ischaemic stroke is
      discussed.

PMID- 10960045
TI  - Abnormal premovement gating of somatosensory input in writer's cramp.
AB  - One characteristic of focal dystonia is the sensory trick, by which sensory input
      to a certain area of the body can reduce abnormal contractions in muscles nearby.
      This suggests that adjusting the link between sensory input and movement allows
      motor commands to be issued more effectively from the brain. To explore this
      sensorimotor link, we studied the attenuation (gating) of somatosensory evoked
      potentials (SEPs) before and during hand movements in patients with writer's
      cramp. For premovement gating, 10 patients and 11 age-matched normal subjects
      were given a warning sound followed 1s later by an electric stimulus to the right
      median nerve at the wrist. The latter served both as a reaction signal to start a
      finger extension task and as the input to evoke SEPs over the scalp. Because
      reaction times always exceeded 70 ms, short-latency SEPs thus obtained were
      unaffected by the afferents activated by the movement. The amplitudes of frontal
      N30 components were significantly decreased over the frontal leads compared with
      SEPs elicited at rest (P: < 0.002) in the normal group, whereas significant
      gating was found not for N30 but for frontal P22 (P: = 0. 002) in the patient
      group. For midmovement gating studies, SEPs to the right median nerve stimulation
      were recorded in 16 patients and 12 age-matched normal subjects at rest, and
      during active and passive finger extension-flexion movements. In contrast to the
      premovement SEPs, the frontal N30 was equally gated during active and passive
      movements both in the patient (P: < or = 0.002) and the normal group (P: < or =
      0.003). These findings indicate that in writer's cramp the sensitivity of sensory
      input channels from the hand is wrongly set by the central command to move.
      Perhaps the sensory trick, by supplying additional input not usually present
      during unobstructed movement, is a manoeuvre to correct this imbalance. Dystonia
      may result not only from abnormalities in the central motor command but also from
      disturbed central processing of sensory input.

PMID- 10960046
TI  - Nitric oxide-induced headache in patients with chronic tension-type headache.
AB  - An experimental model of headache offers unique possibilities to study the
      mechanisms responsible for head pain. Using the glyceryl trinitrate [GTN; nitric
      oxide (NO) donor] model of experimental headache, we studied the intensity,
      quality and time profile of headache after infusion of GTN in 16 patients with
      chronic tension-type headache and in 16 healthy controls. Subjects were
      randomized to receive intravenous infusion of GTN (0.5 microg/kg per minute for
      20 min) or placebo on two headache-free days separated by at least 1 week.
      Headache intensity was measured on a 10-point verbal rating scale during 2 h of
      observation and for the next 10 h after discharge from hospital. The primary
      endpoints were the difference between the area under the curve (AUC-intensities x
      duration) for headache recorded on the day of GTN treatment and on the day of
      placebo treatment in patients, and in patients and controls on the days of GTN
      treatment. In patients, the AUC on a GTN day [2221 (1572-3704); median with
      quartiles in parentheses], was significantly greater than on a placebo day [730
      (60-1678), P: = 0. 008]. On the GTN day, the AUC in patients [2221 (1572-3704)]
      was significantly higher than in controls [43 (0-972), P: = 0.0001]. In patients,
      peak pain intensity occurred 8 h after infusion of GTN, whereas in controls it
      occurred 20 min after the start of infusion. The present study demonstrates that
      an NO-induced biphasic response with an immediate and a delayed headache is
      common to chronic tension-type headache and migraine. Furthermore, the NO-induced
      delayed headache has the characteristics of the primary headache disorder. This
      suggests that NO contributes to the mechanisms of several types of primary
      headaches and that NO-related central sensitization may be an important common
      denominator in the pain mechanisms of primary headaches.

PMID- 10960047
TI  - Abnormal regional cerebral blood flow in childhood autism.
AB  - Neuroimaging studies of autism have shown abnormalities in the limbic system and
      cerebellar circuits and additional sites. These findings are not, however,
      specific or consistent enough to build up a coherent theory of the origin and
      nature of the brain abnormality in autistic patients. Twenty-three children with
      infantile autism and 26 non-autistic controls matched for IQ and age were
      examined using brain-perfusion single photon emission computed tomography with
      technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the
      relationship between regional cerebral blood flow (rCBF) and symptom profiles.
      Images were anatomically normalized, and voxel-by-voxel analyses were performed.
      Decreases in rCBF in autistic patients compared with the control group were
      identified in the bilateral insula, superior temporal gyri and left prefrontal
      cortices. Analysis of the correlations between syndrome scores and rCBF revealed
      that each syndrome was associated with a specific pattern of perfusion in the
      limbic system and the medial prefrontal cortex. The results confirmed the
      associations of (i) impairments in communication and social interaction that are
      thought to be related to deficits in the theory of mind (ToM) with altered
      perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii)
      the obsessive desire for sameness with altered perfusion in the right medial
      temporal lobe. The perfusion abnormalities seem to be related to the cognitive
      dysfunction observed in autism, such as deficits in ToM, abnormal responses to
      sensory stimuli, and the obsessive desire for sameness. The perfusion patterns
      suggest possible locations of abnormalities of brain function underlying abnormal
      behaviour patterns in autistic individuals.

PMID- 10960048
TI  - Regional axonal loss in the corpus callosum correlates with cerebral white matter
      lesion volume and distribution in multiple sclerosis.
AB  - Previous imaging studies have suggested that there is substantial axonal loss in
      the normal-appearing white matter (NAWM) of brains from multiple sclerosis
      patients and that this axonal loss may be an important determinant of disability.
      Recently, substantial axonal loss in the NAWM has been confirmed directly in post
      mortem tissue. Whether the NAWM changes occur as a consequence of damage to axons
      traversing lesions or to a more diffuse injury process is uncertain. Using
      formalin-fixed brains of eight multiple sclerosis patients and eight age-matched
      controls, we examined the relationship between demyelinating lesion load in three
      volumes of the cerebral white matter and the loss of axons in NAWM of the
      corresponding three projection regions (anterior, middle, posterior) in the
      corpus callosum (CC). There was a significant loss of calculated total number of
      axons crossing the CC in each of the three regions relative to the non-multiple
      sclerosis controls. Strong correlations were found between the regional lesion
      load and both the axonal density (r = -0.673, P: = 0.001) and the total estimated
      number of axons crossing the corresponding projection area in the CC (r = -0.
      656, P: = 0.001) for the patients. This suggests that Wallerian degeneration of
      axons transected in the demyelinating lesions makes a major contribution to the
      substantial, diffuse loss of axons in the NAWM in multiple sclerosis. These
      findings emphasize the need to consider the consequences of multiple sclerosis
      lesions in terms of both local and distant effects in functionally connected
      regions of the brain.

PMID- 10960049
TI  - Striatocapsular haemorrhage.
AB  - Haemorrhages in the striatocapsular area, or striatocapsular haemorrhages (SCHs),
      have been regarded as a single entity, although the area is composed of several
      functionally discrete structures that receive blood supply from different
      arteries. We analysed the morphological and clinical presentations of 215 cases
      of SCHs according to a new classification method we have designed on the basis of
      arterial territories. SCHs were divided into six types: (i) anterior type
      (Heubner's artery); (ii) middle type (medial lenticulostriate artery); (iii)
      posteromedial type (anterior choroidal artery); (iv) posterolateral type
      (posteromedial branches of lateral lenticulostriate artery); (v) lateral type
      (most lateral branches of lateral lenticulostriate artery); and (vi) massive
      type. The anterior type (11%) formed small caudate haematomas, always ruptured
      into the lateral ventricle, causing severe headache, and mild contralateral
      hemiparesis developed occasionally. The outcome was excellent. The middle type
      (7%) involved the globus pallidus and medial putamen, frequently causing
      contralateral hemiparesis and transient conjugate eye deviation to the lesion
      side. About 50% of the patients recovered to normal. The posteromedial type (4%)
      formed very small haematomas in the posterior limb of the internal capsule and
      presented with mild dysarthria, contralateral hemiparesis and sensory deficit,
      with excellent outcome in general. The posterolateral type (33%) affected the
      posterior half of the putamen and posterior limb of the internal capsule and
      presented with impaired consciousness and contralateral hemiparesis with either
      language dysfunction or contralateral neglect. The outcome was fair to poor but
      there were no deaths. The lateral type (21%) formed large elliptical haematomas
      between the putamen and insular cortex. Contralateral hemiparesis with language
      dysfunction or contralateral neglect developed frequently but resolved over
      several weeks. The clinical outcome was relatively excellent except when the
      haematoma size was very large. The massive type (24%) formed huge haematomas
      affecting the entire striatocapsular area. Marked sensorimotor deficits and
      impaired consciousness, ocular movement dysfunctions including the 'wrong-way'
      eyes were observed quite frequently. The outcome was very poor with a case
      fatality rate of 81%. The clinico-radiological presentations suggested its origin
      was the same as the posterolateral type.

PMID- 10960050
TI  - Abnormal patterns of breathing during swallowing in neurological disorders.
AB  - Swallowing momentarily inhibits breathing, and normally the great majority of
      apnoeas which accompany a swallow are followed by expiration (xE swallows). This
      swallowing-breathing interaction is regarded as one of several mechanisms by
      which the airway is protected from aspiration during swallowing. The purpose of
      this study was to investigate the interaction of breathing and swallowing in two
      groups of neurological patients. Twenty-two patients with defined neurological
      disorders involving various structures or pathways (brain, spinal cord and
      peripheral nerves) were studied to determine whether particular lesions resulted
      in breakdown of the normal breathing pattern (22 normal subjects were also
      assessed and their breathing-swallowing pattern was compared with that of
      neurological patients). Subsequently, 32 patients with motor neurone disease
      (MND) were studied to identify factors associated with an abnormal pattern (i.e.
      swallow apnoeas followed by inspiration) and to clarify whether an abnormal
      pattern is related to chest infections, episodes of coughing and choking during
      meals, and prognosis. The swallow apnoea in patients with brain, spinal cord and
      peripheral neurological diseases was followed by inspiration more frequently than
      expected [20/22 (91%) patients compared with 2/22 (9%) of normal subjects, P: <
      0.001], but this was not associated with a specific site of lesion(s). However,
      patients with corticobulbar involvement tended to have post-apnoea inspiration
      more often than those without. MND patients commonly displayed an abnormal
      pattern during swallowing [14/32 (44%) patients] characterized by inspiration
      after swallow, prolonged swallow apnoea and multiple swallows per bolus. Over the
      period of follow-up (12-18 months) this pattern did not predict chest infections,
      coughing and choking episodes during meals or survival. It seems likely that post
      swallowing apnoea inspiration is a non-specific concomitant of disordered
      swallowing and/or breathing rather than being an important mechanism of
      aspiration per se or of symptom production.

PMID- 10960051
TI  - Aberrant T cell migration toward RANTES and MIP-1 alpha in patients with multiple
      sclerosis. Overexpression of chemokine receptor CCR5.
AB  - Trafficking of inflammatory T cells into the central nervous system (CNS) plays
      an important role in the pathogenesis of multiple sclerosis. The directional
      migratory ability of peripheral T cells is associated with interactions of
      chemokines with their receptors expressed on T cells. In this study,
      transmigration of peripheral T cells toward a panel of chemokines was examined in
      patients with multiple sclerosis and healthy individuals using Boyden chemotactic
      transwells. A significantly increased migratory rate preferentially toward RANTES
      and MIP-1alpha, but not other chemokines, was found in T cells obtained from
      multiple sclerosis patients as opposed to healthy individuals (P: < 0.001). The
      migratory T-cell populations represented predominantly Th1/Th0 cells while non
      migratory T cells were enriched for Th2-like cells. The study demonstrated
      further that aberrant migration of multiple sclerosis-derived T cells toward
      RANTES and MIP-1 alpha resulted from overexpression of their receptors (CCR5) and
      could be blocked by anti-CCR5 antibodies. These findings have important
      implications for our understanding of the mechanism underlying aberrant T cell
      trafficking in multiple sclerosis.

PMID- 10960052
TI  - Investigation of the functional correlates of reorganization within the human
      somatosensory cortex.
AB  - Much work in animals and humans has demonstrated the existence of changes in
      topographic organization within the somatosensory cortex (SSC) after amputation
      or nerve injury. Afferent inputs from one area of skin are able to activate novel
      areas of cortex after amputation of an adjacent body part. We have investigated
      the functional consequences of this reorganization in a group of patients with
      nerve injury. Using the microneurographic technique of intraneural
      microstimulation (INMS) we stimulated groups of nerve fibres, within individual
      fascicles proximal to the nerve transection, with small electrical pulses. This
      enabled us to activate the deafferented cortex that had presumably undergone
      remodelling and study the conscious percepts described by the subjects. In 39
      fascicles from 10 subjects, we found that the sensations evoked on INMS were no
      different from those reported previously by subjects with intact nerves. This
      finding suggests that such reorganization within the SSC has little effect on the
      function of deafferented cortical neurones or subcortical relay stations. In a
      separate set of experiments, INMS was performed in 16 nerve fascicles from an
      adjacent non-injured nerve or uninjured fascicle within a partially injured
      nerve. The sensations evoked by INMS in these experiments were also comparable to
      those obtained in normal subjects. This indicates that the expanded cortical
      representation of adjacent non-anaesthetic skin does not influence the cortical
      processing of afferent information. Taken together, these findings lead us to
      question the notion that reorganization of connections within the somatosensory
      cortex equates to a change in function. Whilst it may be advantageous that the
      human brain is not 'hard-wired', neurophysiological proof of functional
      plasticity in the adult somatosensory system as a result of deafferentation is
      elusive.

PMID- 10960053
TI  - 'Secondary' 4216/ND1 and 13708/ND5 Leber's hereditary optic neuropathy
      mitochondrial DNA mutations do not further impair in vivo mitochondrial oxidative
      metabolism when associated with the 11778/ND4 mitochondrial DNA mutation.
AB  - The pathogenic role of 'secondary' mitochondrial DNA (mtDNA) point mutations,
      when occurring in patients with Leber's hereditary optic neuropathy (LHON) in
      association with 'primary' mutations, is still controversial. We used phosphorus
      magnetic resonance spectroscopy to establish whether two of these 'secondary'
      LHON mtDNA mutations, 4216/ND1 and 13708/ND5 (haplogroup J), further affect in
      vivo mitochondrial oxidative metabolism in subjects with the 'primary' 11778/ND4
      mtDNA mutation. Brain and skeletal muscle energy metabolism was assessed in 10
      subjects homoplasmic for the 11778/ND4 mtDNA mutation and 10 subjects homoplasmic
      for the same mutation occurring on the haplogroup J mtDNA background. Brain
      phosphocreatine concentration and phosphorylation potential were significantly
      reduced and brain inorganic phosphate concentration was significantly increased
      compared with controls in both groups of 11778/ND4-positive subjects. The degree
      of reduction in the phosphocreatine concentration and phosphorylation potential
      and of increase in the inorganic phosphate concentration was, however, similar in
      the two groups with the 11778/ND4 mtDNA mutation with or without the haplogroup
      J. Similarly, the rate of muscle phosphocreatine resynthesis after exercise, a
      sensitive index of the rate of mitochondrial ATP production, was reduced by the
      same extent in both groups of LHON subjects. This in vivo study does not support
      synergism of the 4216/ND1 and 13708/ND5 'secondary' mutations with the 11778/ND4
      'primary' mutation in determining the deficit of energy metabolism in LHON.

PMID- 10960054
TI  - Functional delineation of the human occipito-temporal areas related to face and
      scene processing. A PET study.
AB  - By measuring regional cerebral blood flow using PET, we delineated the roles of
      the occipito-temporal regions activated by faces and scenes. We asked right
      handed normal subjects to perform three tasks using facial images as visual
      stimuli: in the face familiar/unfamiliar discrimination (FF) task, they
      discriminated the faces of their friends and associates from unfamiliar ones; in
      the face direction discrimination (FD) task, they discriminated the direction of
      each unfamiliar face; in the dot location discrimination (DL) task, they
      discriminated the location of a red dot on a scrambled face. The activity in each
      task was compared with that in the control fixation (CF) task, in which they
      fixated on the centre of a display without visual stimuli. The DL task activated
      the occipital cortices and posterior fusiform gyri bilaterally. During the FD
      task, the activation extended anteriorly in the right fusiform gyrus and
      laterally to the right inferior temporal cortex. The FF task further activated
      the right temporal pole. To examine whether the activation due to faces was face
      specific, we used a scene familiar/unfamiliar discrimination (SF) task, in which
      the subjects discriminated familiar scenes from unfamiliar ones. Our results
      suggest that (i) the occipital cortices and posterior fusiform gyri non
      selectively respond to faces, scrambled faces and scenes, and are involved mainly
      in the extraction of physical features of complex visual images; (ii) the right
      inferior temporal/fusiform gyrus responds selectively to faces but not to non
      face stimuli and is involved in the visual processing related to face perception,
      whereas the bilateral parahippocampal gyri and parieto-occipital junctions
      respond selectively to scenes and are involved in processing related to scene
      perception; and (iii) the right temporal pole is activated during the
      discrimination of familiar faces and scenes from unfamiliar ones, and is probably
      involved in the recognition of familiar objects.

PMID- 10960055
TI  - The role of conceptual knowledge in object use evidence from semantic dementia.
AB  - It has been reported that patients with semantic dementia function well in
      everyday life and sometimes show striking preservation of the ability to use
      objects, even those specific objects for which the patient has degraded
      conceptual information. To explore this phenomenon in nine cases of semantic
      dementia, we designed a set of semantic tests regarding 20 everyday objects and
      compared performance on these with the patients' ability to demonstrate the
      correct use of the same items. We also administered a test of mechanical problem
      solving utilizing novel tools, on which the patients had completely normal
      ability. All but the mildest affected patient showed significant deficits of
      naming and on the visually based semantic matching tasks. Object use was markedly
      impaired and, most importantly, correlated strongly with naming and semantic
      knowledge. In a small number of instances, there was appropriate use of an object
      for which the patient's knowledge on the semantic matching tasks was no better
      than chance; but this typically applied to objects with a rather obvious
      relationship between appearance and use, or was achieved by trial and error. The
      results suggest that object use is heavily dependent upon object-specific
      conceptual knowledge, supplemented to some degree by a combination of visual
      affordances and mechanical problem solving.

PMID- 10960056
TI  - Patterns of music agnosia associated with middle cerebral artery infarcts.
AB  - The objective of the study is to evaluate if the rupture of an aneurysm located
      on the middle cerebral artery (MCA) results in disorders of music recognition. To
      this aim, 20 patients having undergone brain surgery for the clipping of a
      unilateral left (LBS), right (RBS) or bilateral (BBS) aneurysm(s) of the MCA and
      20 neurologically intact control subjects (NC) were evaluated with a series of
      tests assessing most of the abilities involved in music recognition. In general,
      the study shows that a ruptured aneurysm on the MCA that is repaired by brain
      surgery is very likely to produce deficits in the auditory processing of music.
      The incidence of such a deficit was not only very high but also selective. The
      results show that the LBS group was more impaired than the NC group in all three
      tasks involving musical long-term memory. The study also uncovered two new cases
      of apperceptive agnosia for music. These two patients (N.R. and R.C.) were
      diagnosed as such because both exhibit a clear deficit in each of the three music
      memory tasks and both are impaired in all discrimination tests involving musical
      perception. Interestingly, the lesions overlap in the right superior temporal
      lobe and in the right insula, making the two new cases very similar to an earlier
      case report. Altogether, the results are also consistent with the view that
      apperceptive agnosia results from damage to right hemispheric structures while
      associative agnosia results from damage to the left hemisphere.

PMID- 10960057
TI  - Time-dependent activation of parieto-frontal networks for directing attention to
      tactile space. A study with paired transcranial magnetic stimulation pulses in
      right-brain-damaged patients with extinction.
AB  - Tactile extinction has been interpreted as an attentional disorder, closely
      related to hemineglect, due to hyperactivation of the unaffected hemisphere,
      resulting in an ipsilesional attentional bias. Paired transcranial magnetic
      stimulation (TMS) techniques, with a subthreshold conditioning stimulus (CS)
      followed at various interstimulus intervals (ISIs) by a suprathreshold test
      stimulus (TS), are useful for investigating intracortical inhibition and
      facilitation in the human motor cortex. In the present work, we investigated the
      effects of paired TMS over the posterior parietal and frontal cortex of the
      unaffected hemisphere in a group of eight right-brain-damaged patients with
      tactile extinction who were carrying out a bimanual tactile discrimination task.
      The aim of the study was to verify if paired TMS could induce selective
      inhibition or facilitation of the unaffected hemisphere depending on the ISI,
      resulting, respectively, in an improvement and a worsening of contralesional
      extinction. In addition, we wanted to investigate if the effects of parietal and
      frontal TMS on contralesional extinction appeared at different intervals,
      suggesting time-dependent activation in the cortical network for the processing
      of tactile spatial information. Paired TMS stimuli with a CS and a TS, separated
      by two ISIs of 1 and 10 ms, were applied over the left parietal and frontal
      cortex after various intervals from the presentation of bimanual cutaneous
      stimuli. Single-test parietal TMS stimuli improved the patients' performance,
      whereas paired TMS had distinct effects depending on the ISI: at ISI = 1 ms the
      improvement in extinction was greater than that induced by single-pulse TMS; at
      ISI = 10 ms we observed worsening of extinction, with complete reversal of the
      effects of single-pulse TMS. Compared with TMS delivered over the frontal cortex,
      parietal TMS improved the extinction rate in a time window that began earlier.
      These findings shed further light on the mechanism of tactile extinction,
      suggesting relative hyperexcitability of the parieto-frontal network in the
      unaffected hemisphere, which is amenable to study and modulation by paired TMS
      pulses. In addition, the results show time-dependent processing of tactile
      spatial information in the parietal and frontal cortices, with a bimodal
      distribution of activity, at least in the attentional network of the unaffected
      hemisphere.

PMID- 10960058
TI  - Word repetition in amnesia. Electrophysiological measures of impaired and spared
      memory.
AB  - Amnesic patients often show improved performance when stimuli are repeated, even
      in the absence of conscious memory for those stimuli. Although these performance
      changes are typically attributed to perceptual or motor systems, in some cases
      they may be related to basic language processing. We examined two
      neurophysiological measures that vary with word repetition in 12 amnesic patients
      and 12 control subjects: (i) a late positive component of the event-related
      potential (ERP) linked to conscious memory and (ii) the N400 component that
      varies with language comprehension. In each trial, the subject heard a category
      name, then viewed a word, and then decided whether the word was semantically
      congruous or incongruous (e.g. 'yes' for 'baby animal: cub'; 'no' for 'water
      sport: kitchen'). Recall and recognition testing at the end of the experiment
      showed that control subjects had better memory for congruous than for incongruous
      words, as did the amnesic patients, who performed less well overall. In contrast,
      amnesic patients were unimpaired on the category decisions required in each trial
      and, like the control subjects, showed a large N400 for incongruous relative to
      congruous words. Similarly, when incongruous trials were repeated after 0-13
      intervening trials, N400s were reduced in both groups. When congruous trials were
      repeated, a late positive repetition effect was observed, but only in the control
      group. Furthermore, the amplitude of the late positive repetition effect was
      highly correlated with later word recall in both patients and controls. In the
      patients, the correlation was also observed with memory scores from standardized
      neuropsychological tests. These data are consistent with a proposed link between
      the late positive repetition effect and conscious memory. On the other hand, the
      N400 repetition effect was not correlated with episodic memory abilities, but
      instead indexed an aspect of memory that was intact in the amnesic patients. The
      preserved N400 repetition effect is an example of preserved memory in amnesia
      that does not easily fit into the categories of low-level perceptual processing
      or of motor learning. Instead, the sensitivity of the N400 to both semantic
      context and repetition may reflect a short-term memory process that serves
      language comprehension in realtime.

PMID- 10960059
TI  - Reproducibility of peer review in clinical neuroscience. Is agreement between
      reviewers any greater than would be expected by chance alone?
AB  - We aimed to determine the reproducibility of assessments made by independent
      reviewers of papers submitted for publication to clinical neuroscience journals
      and abstracts submitted for presentation at clinical neuroscience conferences. We
      studied two journals in which manuscripts were routinely assessed by two
      reviewers, and two conferences in which abstracts were routinely scored by
      multiple reviewers. Agreement between the reviewers as to whether manuscripts
      should be accepted, revised or rejected was not significantly greater than that
      expected by chance [kappa = 0.08, 95% confidence interval (CI) -0.04 to -0.20]
      for 179 consecutive papers submitted to Journal A, and was poor (kappa = 0.28,
      0.12 to 0. 40) for 116 papers submitted to Journal B. However, editors were very
      much more likely to publish papers when both reviewers recommended acceptance
      than when they disagreed or recommended rejection (Journal A, odds ratio = 73,
      95% CI = 27 to 200; Journal B, 51, 17 to 155). There was little or no agreement
      between the reviewers as to the priority (low, medium, or high) for publication
      (Journal A, kappa = -0.12, 95% CI -0.30 to -0.11; Journal B, kappa = 0.27, 0.01
      to 0.53). Abstracts submitted for presentation at the conferences were given a
      score of 1 (poor) to 6 (excellent) by multiple independent reviewers. For each
      conference, analysis of variance of the scores given to abstracts revealed that
      differences between individual abstracts accounted for only 10-20% of the total
      variance of the scores. Thus, although recommendations made by reviewers have
      considerable influence on the fate of both papers submitted to journals and
      abstracts submitted to conferences, agreement between reviewers in clinical
      neuroscience was little greater than would be expected by chance alone.

PMID- 10960060
TI  - Prevention by dexrazoxane of down-regulation of ryanodine receptor gene
      expression in anthracycline cardiomyopathy in the rat.
AB  - Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by
      changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum
      (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine
      receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF-187),
      an iron chelator which prevents anthracycline cardiotoxicity, on RyR2 gene
      expression in rats treated chronically with daunorubicin. Daunorubicin (2.5 mg
      kg(-1) i.v. weekly for 6 weeks) produced cardiotoxicity as demonstrated by
      histopathologic changes. The ryanodine receptor/glyceraldehyde phosphate
      dehydrogenase (GAPDH) mRNA ratio was decreased by 38+/-3% (P<0.02) compared to
      values in control rats. Dexrazoxane pre-treatment (50 mg kg(-1); 1 h prior to
      each daunorubicin injection) prevented the decrease in RyR2/GAPDH mRNA ratio and
      histopathologic lesions in daunorubicin-treated rats. This is the first report
      that a protective agent such as dexrazoxane can ameliorate the decreased
      expression of a specific gene involved in anthracycline-induced cardiotoxicity.

PMID- 10960062
TI  - Human urotensin-II is a potent spasmogen of primate airway smooth muscle.
AB  - The contractile profile of human urotensin-II (hU-II) was examined in primate
      airway and pulmonary vascular tissues. hU-II contracted tissues from different
      airway regions with similar potencies (pD(2)s from 8.6 to 9.2). However, there
      were regional differences in the efficacy of hU-II, with a progressive increase
      in the maximum contraction from trachea to smaller airway regions (from 9 to 41%
      of the contraction to 10 microM carbachol). hU-II potently contracted pulmonary
      artery tissues from different regions with similar potencies and efficacies:
      pD(2)s=8.7 to 9.3 and maximal contractions=79 to 86% of 60 mM KCl. hU-II potently
      contracted pulmonary vein preparations taken proximal to the atria, but had no
      effect in tissues from distal to the atria. This is the first report describing
      the contractile activity of hU-II in airways and suggests that the potential
      pathophysiological role of this peptide in lung diseases warrants investigation.

PMID- 10960061
TI  - Inhibition of sustained hypoxic vasoconstriction by Y-27632 in isolated
      intrapulmonary arteries and perfused lung of the rat.
AB  - We have examined the effects of Y-27632, a specific inhibitor of Rho-activated
      kinases (ROCK I and ROCK II) upon sustained hypoxic pulmonary vasoconstriction
      (HPV) in both rat isolated small intrapulmonary arteries (IPA) and perfused rat
      lungs in situ. Y-27632 (100 nM - 3 microM) was found to cause a concentration
      dependent inhibition of acute sustained HPV in rat IPA. Application of Y-27632
      (10-600 nM) in perfused rat lungs caused no change in basal perfusion pressure,
      but was found to inhibit HPV in a concentration-dependent manner, resulting in
      complete ablation of the pressor response to hypoxia at a concentration of 600
      nM. Furthermore, addition of Y-27632 at any point during hypoxia caused a
      reversal of HPV in perfused rat lungs. These results suggest that activation of
      Rho-associated kinase may be a pivotal step in the generation of sustained HPV.

PMID- 10960063
TI  - Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal
      transduction has anti-inflammatory effects and interacts with glucocorticoid
      receptor in vivo.
AB  - Histamine, vascular endothelial growth factor, acetylcholine, oestrogen as well
      as fluid shear stress activates a mechanism that recruits heat shock protein 90
      to the endothelial nitric oxide synthase. The interaction between Hsp90 and eNOS
      enhances the activation of the enzyme in cells and in intact blood vessels
      leading to NO production. Intraplantar administration of carrageenan (50 microl
      paw(-1)) to mice causes an oedema lasting 72 h. Geldanamycin (0.1, 0.3, 1 mg kg(
      1)), a specific inhibitor of Hsp-90, that inhibits endothelium-dependent
      relaxations of the rat aorta, mesentery and middle artery inhibits carrageenan
      induced mouse paw oedema in a dose dependent manner. Co-administration to mice of
      dexamethasone (1 mg kg(-1)) with geldanamycin (0.3 mg kg(-1)) at anti
      inflammatory dose causes a loss of the total anti-inflammatory effect of each
      agent alone. RU 486 (10 mg kg(-1)), a well known glucocorticoid receptorial
      antagonist, does not inhibit oedema formation but prevents the anti-inflammatory
      action of dexamethasone (1 mg kg(-1)). Similarly, RU 486 prevents the anti
      inflammatory action of geldanamycin (0.3 mg kg(-1)). In conclusion we have
      described for the first time that geldanamycin, an inhibitor of Hsp90 dependent
      signal transduction, is anti-inflammatory in vivo implying that Hsp90 is critical
      for pathways involved in carrageenan-induced paw oedema. In addition the ability
      of GA to block NO release and reduce oedema formation suggests a therapeutic
      rationale for specific inhibitors of Hsp90 as potential anti-inflammatory drugs.

PMID- 10960065
TI  - Inducible nitric oxide synthase-derived superoxide contributes to hypereactivity
      in small mesenteric arteries from a rat model of chronic heart failure.
AB  - The aims of this study were to (a) determine whether inducible nitric oxide
      synthase (iNOS) is expressed in small mesenteric arteries from rats with chronic
      heart failure (CHF), (b) investigate the functional significance of this
      potential source of nitric oxide (NO) on vascular responsiveness and (c)
      investigate the role that superoxide plays in modulating vascular function in
      these arteries. CHF was induced in male Wistar rats by coronary artery ligation
      (CAL). In sham-operated rats the ligature was not tied but pulled under the
      artery. Six weeks after surgery CAL rats had left ventricular (LV) infarctions
      and elevated LV end-diastolic pressures. Immunoreactive iNOS was found in
      endothelial cells, vascular smooth muscle cells and in the adventitia of small
      mesenteric arteries from CAL rats but not those from sham-operated rats. Third
      order mesenteric arteries (300-350 microm) were mounted in a small vessel
      pressure myograph. Endothelium-intact arteries from CAL rats were more responsive
      to phenylephrine (PE) than arteries from sham-operated rats (pD(2) value, CAL,
      6.2+/-0.1; sham-operated, 5.9+/-0.1, P<0.05). Both the selective iNOS inhibitor,
      N-(3-(Aminomethyl) benzyl) acetamidine dihydrochloride (1400W; 10(-6) M) and the
      superoxide dismutase mimetic, Mn [III] tetrakis [1-methyl-4-pyridyl] porphyrin,
      (MnTMPyP; 10(-4) M) reversed the hyperesponsiveness (pD(2) values, 1400W, 5.9+/
      0.1; MnTMPyP, 5.81+/-0.1, P<0.05). The NOS substrate, L-arginine (10(-3) M),
      reduced responsiveness of endothelium-denuded small mesenteric arteries from CAL
      rats (P<0.01). None of these drugs altered responses to PE in arteries from sham
      operated rats. In summary, this study demonstrates that iNOS is expressed in
      mesenteric arteries from rats with CHF. However, instead of generating large
      quantities of NO, iNOS appears to be generating superoxide, perhaps because of a
      deficiency in its substrate, L-arginine. Increased superoxide generation from
      iNOS contributes to the hyperesponsive nature of endothelium-intact small
      mesenteric arteries from rats with CHF.

PMID- 10960064
TI  - The importance of ERK activity in the regulation of cyclin D1 levels and DNA
      synthesis in human cultured airway smooth muscle.
AB  - The relationship between persistent ERK (extracellular signal-regulated kinase)
      activity, cyclin D1 protein and mRNA levels and cell cycle progression in human
      cultured airway smooth muscle was examined in response to stimulation by ET-1
      (endothelin-1), thrombin and bFGF (basic fibroblast growth factor). Thrombin (0.3
      and 3 u ml(-1)) and bFGF (0.3 and 3 nM) increased ERK activity for more than 2 h
      and increased cell number, whereas ET-1 (100 nM) transiently stimulated ERK
      activity and was non-mitogenic. The MEK1 (mitogen-activated ERK kinase)
      inhibitor, PD 98059 (30 microM), inhibited both ERK phosphorylation and activity,
      and either prevented (thrombin 0.3 and 3 u ml(-1), bFGF 300 pM) or attenuated
      (bFGF 3 nM) DNA synthesis. Thrombin and bFGF increased both cyclin D1 mRNA and
      protein levels. PD 98059 decreased cyclin D1 protein levels stimulated by the
      lower but not higher thrombin concentrations. Moreover, increases in cyclin D1
      mRNA levels were unaffected by PD 98059 pretreatment, irrespective of the mitogen
      or its concentration, suggesting that inhibition of cyclin D1 protein levels
      occurred by a post-transcriptional mechanism. These findings indicate that the
      control of cyclin D1 protein levels may occur independently of the MEK1/ERK
      signalling pathways. The inhibition of S phase entry by PD 98059 at higher
      thrombin concentrations appears to result from effects on pathways downstream or
      parallel to those regulating cyclin D1 protein levels. These findings suggest
      heterogeneity in the signalling of DNA synthesis in human cultured airway smooth
      muscle.

PMID- 10960066
TI  - Characterization of changes in mechanical responses to histamine in omental
      resistance arteries in pre-eclampsia.
AB  - Changes in the effect of histamine on the smooth muscle of resistance arteries in
      pre-eclampsia were investigated by measuring isometric contractions in
      endothelium-denuded strips of omental resistance arteries from pre-eclamptic and
      normotensive pregnant women (pregnancy-term matched). Histamine (0.03 -1 microM)
      caused concentration-dependent relaxation of the contraction induced by 9, 11
      epithio-11,12-methano-thromboxane A(2) (STA(2)) in strips from both groups.
      Sensitivity (for pre-eclampsia: pD(2)=6.66+/-0.04, n=5 and for normotensive
      pregnant women: pD(2)=7.07+/-0.03, n=10, P<0.001) was lower and the maximum
      response (90.6+/-0.6% vs 95.5+/-1.1%, P<0.05) was smaller in strips from pre
      eclamptic women. Although 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Sp
      isomer: Sp-8-Br-cAMPS, 0.1 - 0.3 mM), a phosphodiesterase (PDE)-resistant
      activator of adenosine-3',5'-cyclic monophosphate (cyclic AMP)-dependent protein
      kinase, concentration-dependently attenuated the contraction induced by STA(2) in
      strips from both groups, the sensitivity (for pre-eclampsia: pD(2)=3.68+/-0.04,
      n=5 and for normotensive pregnant women: 3.94+/-0.09, n=7, P:=0.02) was lower and
      the maximum response (64.2+/-2.4% vs 74.9+/-4.4%, P:<0.05) was smaller in pre
      eclampsia. In beta-escin-skinned strips, the pD(2) value for the contraction
      inducing effect of Ca(2+) did not differ significantly between the two groups
      (for pre-eclampsia, n=6; for normotensive pregnant women, n=6). Thus, omental
      resistance arteries from human subjects with pre-eclampsia showed (i) a weaker
      H(2)-receptor-mediated relaxation to histamine and (ii) a weaker cyclic AMP
      analogue-induced relaxation, suggesting that the reduced action of histamine may
      be partly due to a decreased effect of cyclic AMP.

PMID- 10960067
TI  - Study of A(2A) adenosine receptor gene deficient mice reveals that adenosine
      analogue CGS 21680 possesses no A(2A) receptor-unrelated lymphotoxicity.
AB  - Cell surface A(2A) adenosine receptor (A(2A)R) mediated signalling affects a
      variety of important processes and adenosine analogues possess promising
      pharmacological properties. Demonstrating the receptor specificity of potentially
      lymphotoxic adenosine-based drugs facilitates their development for clinical
      applications. To distinguish between the receptor-dependent and -independent
      lymphotoxicity and apoptotic activity of adenosine and its analogues we used
      lymphocytes from A(2A)R-deficient mice. Comparison of A(2A)R-expressing (+/+) and
      A(2A)R-deficient (-/-) cells in cyclic AMP accumulation assays confirmed that the
      A(2A)R agonist CGS 21680 is indeed selective for A(2A) receptors in T
      lymphocytes. Incubation of A(2A)R-expressing thymocytes with extracellular
      adenosine or CGS 21680 in vitro results in the death of about 7-15% of
      thymocytes. In contrast, no death was induced in parallel assays in cells from
      A(2A)R-deficient mice, providing genetic evidence that CGS 21680 does not display
      adenosine receptor-independent intracellular cytotoxicity. The A(2A) receptor
      specific lymphotoxicity of CGS 21680 is also demonstrated in a long-term (6-day)
      in vitro model of thymocyte positive selection where addition of A(2A)R
      antagonist ZM 241,385 did block the effects of CGS 21680, allowing the survival
      of T cells. The use of cells from adenosine receptor-deficient animals is
      proposed as a part of the screening process for potential adenosine-based drugs
      for their receptor-independent cytotoxicity and lymphotoxicity.

PMID- 10960068
TI  - The stable pyrimidines UDPbetaS and UTPgammaS discriminate between the P2
      receptors that mediate vascular contraction and relaxation of the rat mesenteric
      artery.
AB  - The contractile and relaxant effects of the different P2 receptors were
      characterized in the rat isolated mesenteric artery by use of extracellular
      nucleotides, including the stable pyrimidines uridine 5'-O-thiodiphosphate
      (UDPbetaS) and uridine 5'-O-3-thiotriphosphate (UTPgammaS). The selective P2X
      receptor agonist, alphabeta-methylene-adenosine triphosphate (alphabeta-MeATP)
      stimulated a potent (pEC(50)=6.0) but relatively weak contraction (E:(max)=57% of
      60 mM K(+)). The contractile concentration-response curve of adenosine
      triphosphate (ATP) was biphasic when added in single concentrations. The first
      part of the response could be desensitized by alphabeta-MeATP, indicating
      involvement of P2X receptors, while the second part might be mediated by P2Y
      receptors. The contractile P2Y receptors were further characterized after P2X
      receptor desensitization with 10 microM alphabeta-MeATP. Uridine diphosphate
      (UDP), uridine triphosphate (UTP) and ATP stimulated contraction only in high
      concentrations (1 - 10 mM). The selective P2Y(6) agonist, UDPbetaS, and the
      P2Y(2)/P2Y(4)-receptor agonists UTPgammaS and adenosine 5'-O-3-thiotriphosphate
      (ATPgammaS) were considerably more potent and efficacious (E:(max) approximately
      250% of 60 mM K(+)). Adenosine 5'-O-thiodiphosphate (ADPbetaS) was inactive,
      excluding contractile P2Y(1) receptors. After precontraction with 1 microM
      noradrenaline, UTP, ADP and ATP induced relaxations with similar potencies
      (pEC(50) approximately 5.0). UTPgammaS, ADPbetaS and ATPgammaS were approximately
      one log unit more potent indicating the presence of endothelial P2Y(1) and
      P2Y(2)/P2Y(4) receptors. The P2Y(6) receptor agonist, UDPbetaS, had no effect.
      UDPbetaS and UTPgammaS are useful tools when studying P2 receptors in tissue
      preparations with ectonucleotidase activity. Contractile responses can be
      elicited by stimulation of P2Y(6) and, slightly less potently, P2Y(2)/P2Y(4)
      receptors. The P2X response was relatively weak, and there was no P2Y(1)
      response. Stimulation of P2Y(1) and P2Y(2)/P2Y(4) receptors elicited relaxation,
      while P2Y(6) did not contribute.

PMID- 10960069
TI  - Probenecid interferes with renal oxidative metabolism: a potential pitfall in its
      use as an inhibitor of drug transport.
AB  - The anionic drug probenecid has been traditionally used as an inhibitor of renal
      organic anion transport. More recently the drug was found to inhibit organic
      cation transport as well, and it is used to retain intracellularly loaded
      fluorophores. In these investigations it is implicitly assumed that probenecid
      performs its activity through competition for transport. Here we studied the
      possibility that probenecid provokes its effect through inhibition of cellular
      oxidative metabolism. Oxygen consumption was measured in isolated rat kidney
      cortex mitochondria. At concentrations of 1 mM or higher, probenecid increased
      the resting state (state 4) and decreased the ADP-stimulated respiration (state
      3). A complete loss in respiratory control was observed at 10 mM probenecid.
      After incubating isolated rat kidney proximal tubular cells (PTC) for 30 min with
      probenecid a concentration-dependent reduction in ATP content was observed, which
      was significant at concentrations of 1 mM and higher. Using digital image
      fluorescence microscopy the membrane potential in PTC was measured with
      bisoxonol. The mitochondrial effects of probenecid were paralleled by a
      depolarization of the plasma membrane, immediately after drug addition. All
      events are likely to be a result of membrane disordering due to the lipophilic
      character of probenecid, and may explain, at least in part, the various
      inhibitory effects found for the drug. We recommend to be cautious with applying
      probenecid in cellular research.

PMID- 10960070
TI  - YM-53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and
      triglyceride levels in several animal species.
AB  - The aim of this study was to evaluate the potency of YM-53601 ((E)-2-[2-fluoro-2
      (quinuclidin-3-ylidene) ethoxy]-9H-carbazole monohydrochloride), a new inhibitor
      of squalene synthase, in reducing both plasma cholesterol and triglyceride
      levels, compared with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor and fibrates, respectively. YM-53601 equally inhibited squalene
      synthase activities in hepatic microsomes prepared from several animal species
      and also suppressed cholesterol biosynthesis in rats (ED(50), 32 mg kg(-1)). In
      guinea-pigs, YM-53601 and pravastatin reduced plasma nonHDL-C (=total cholesterol
      - high density lipoprotein cholesterol) by 47% (P<0.001) and 33% (P<0.001),
      respectively (100 mg kg(-1), daily for 14 days). In rhesus monkeys, YM-53601
      decreased plasma nonHDL-C by 37% (50 mg kg(-1), twice daily for 21 days, P<0.01),
      whereas the HMG-CoA reductase inhibitor, pravastatin, failed to do (25 mg kg(-1),
      twice daily for 28 days). YM-53601 caused plasma triglyceride reduction in
      hamsters fed a normal diet (81% decrease at 50 mg kg(-1), daily for 5 days,
      P<0.001). In hamsters fed a high-fat diet, the ability of YM-53601 to lower
      triglyceride (by 73%, P<0.001) was superior to that of fenofibrate (by 53%,
      P<0.001), the most potent fibrate (dosage of each drug: 100 mg kg(-1), daily for
      7 days). This is the first report that a squalene synthase inhibitor is superior
      to an HMG-CoA reductase inhibitor in lowering plasma nonHDL-C level in rhesus
      monkeys and is superior to a fibrate in significantly lowering plasma
      triglyceride level. YM-53601 may therefore prove useful in treating
      hypercholesterolemia and hypertriglyceridemia in humans.

PMID- 10960071
TI  - The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor
      antagonists across the apical membrane of renal LLC-PK(1) cell monolayers.
AB  - Previous studies have shown that beta-adrenoceptor antagonists may be substrates
      of organic cation transporters in kidney and lung. In this study we examined the
      transport of the beta-adrenoreceptor antagonists propranolol and metoprolol, in
      renal LLC-PK(1) cell monolayers. Experiments with BCECF (2', 7'
      bis(2carboxyethyl)-5(6)-carboxyfluorescein) loaded LLC-PK(1) cell monolayers
      demonstrated that metoprolol and propranolol flux across the basolateral membrane
      was consistent with non-ionic diffusion. Flux across the apical membrane
      consisted of both non-ionic diffusion and the uptake of the cationic form of the
      beta-adrenoceptor antagonists. Uptake of the cationic form of metoprolol across
      the apical membrane was Na(+)-independent, electrogenic and sensitive to external
      pH. Furthermore, uptake was sensitive to inhibition by Decynium-22 and the
      organic cations TEA (tetraethylammonium) and MPP(+) (1-methyl 4
      phenylpyridinium). These results, allied with the apical location of the uptake
      mechanism suggest that beta-adrenoceptor antagonists may be substrates for the
      organic cation transporter, OCT2. To confirm beta-adrenoceptor antagonists as
      substrates for OCT2, we demonstrate, in cells transiently transfected with an
      epitope tagged version of hOCT2 (hOCT2-V5):(1) Decynium-22 sensitive [(14)C]
      propranolol uptake, (2) cis-inhibition of OCT2 by a range of beta-adrenoceptor
      antagonists and (3) metoprolol induced intracellular acidification.

PMID- 10960072
TI  - Inhibitory effect of amiodarone on Na(+)/Ca(2+) exchange current in guinea-pig
      cardiac myocytes.
AB  - The effect of amiodarone on Na(+)/Ca(2+) exchange current (I(NCX)) was examined
      in single guinea-pig ventricular myocytes using the whole-cell voltage clamp
      technique. I(NCX) was recorded by ramp pulses from the holding potential of -60
      mV in the presence of 140 mM Na(+) and 2 mM Ca(2+) in the external solution, and
      20 mM Na(+) and 398 nM free Ca(2+) (19 mM Ca(2+) and 30 mM BAPTA) in the internal
      solution. External application of amiodarone suppressed I(NCX) in a concentration
      dependent manner. The IC(50) value was 3.3 microM with a Hill coefficient of 1.
      Intracellular application of trypsin via the micropipette attenuated the blocking
      effect of amiodarone, suggesting that amiodarone affects the cytoplasmic side of
      the molecule. This inhibitory effect of amiodarone on the Na(+)/Ca(2+) exchanger
      may contribute to the cardioprotective action of the drug.

PMID- 10960073
TI  - Influence of cannabinoids on the delayed rectifier in freshly dissociated smooth
      muscle cells of the rat aorta.
AB  - The influence of the cannabinoids anandamide, methanandamide and WIN 55212-2 on
      the delayed rectifier K(+) current (I(K(V))) in rat arterial myocytes was
      investigated. Anandamide caused a concentration-dependent reduction of total peak
      and late K(+) current (I(K)). The maximal effect (about 50% inhibition of I(K))
      was reached with 3 microM, and half-maximal current block was observed at 0.6
      microM. Blockade was voltage-independent. Inhibition of I(K) by the cannabinoid
      was associated with a characteristic increase in the rate of current relaxation.
      Methanandamide (10 microM), a metabolically more stable analogue of anandamide,
      decreased I(K) with a similar time course. Current traces in the presence of the
      drug also showed an acceleration of inactivation. The presence of TEA did not
      impair the inhibition by anandamide or methanandamide, but inhibition was
      prevented by pre-exposure to 4-AP, showing that both cannabinoids inhibited
      I(K(V)) while having no influence on Ca(2+)-dependent K(+) current (I(K(Ca))).
      The CB(1) receptor antagonist SR141716A (10 microM) did not influence the action
      of anandamide or methanandamide. Arachidonic acid (1 microM) increased I(K)
      considerably. However, in the presence of TEA it caused a decrease of I(K(V))
      with a characteristic increase in the rate of current relaxation. WIN 55212-2 (20
      microM) caused similar inhibition of I(K). Internally applied anandamide (10
      microM) or methanandamide (10 microM) was ineffective at influencing I(K). In the
      dialyzed cells, the additional external application of a cannabinoid promptly
      initiated inhibition. The results show that anandamide, methanandamide and WIN
      55212-2 affect I(K(V)) in a cannabinoid receptor-independent way similar to that
      of arachidonic acid, which, unlike the cannabinoids, additionally increases a
      Ca(2+)-activated K(+) current. It is suggested that cannabinoids might bind to an
      external site on or near the K(v) channel of the vascular smooth muscle cells.

PMID- 10960074
TI  - Modulation of acetylcholine release in the guinea-pig trachea by the nitric oxide
      donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP).
AB  - The effects of the nitric oxide (NO) donor S-nitroso-N-acetyl-DL-penicillamine
      (SNAP) and the NO synthase inhibitor L-N(G)-nitroarginine (L-NOARG) on the
      electrically evoked [(3)H]-acetylcholine release were studied in an epithelium
      free preparation of guinea-pig trachea that had been preincubated with [(3)H]
      choline. SNAP (100 and 300 microM) caused small but significant increases of the
      electrically evoked [(3)H]-acetylcholine release (121+/-4% and 124+/-10% of
      control). Resting outflow of [(3)H]-ACh was not affected by SNAP. The increase by
      SNAP was abolished by the specific inhibitor of soluble guanylyl cyclase, 1H
      [1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 1 microM). The facilitatory
      effect of SNAP (100 and 300 microM) was reversed into inhibition of release (to
      74+/-4% and to 78+/-2%) after pretreatment of the trachea with capsaicin (3
      microM). ODQ prevented the inhibition. Capsaicin pretreatment alone did not
      significantly alter the release of [(3)H]-acetylcholine. A significant inhibition
      by SNAP (100 microM) of [(3)H]-acetylcholine release (78+/-3%) was also seen in
      the presence of the NK(2) receptor antagonist SR 48968 (30 nM). L-NOARG (10 and
      100 microM) significantly enhanced the electrically-evoked smooth muscle
      contractions, but caused no significant increases of the evoked release from
      capsaicin pretreated trachea strips. This might indicate that the inhibitory
      effect of endogenous NO on acetylcholine release is too small to be detected by
      overflow studies. It is concluded that NO has dual effects on the evoked
      acetylcholine release. NO enhances release in the absence of modifying drugs, but
      NO inhibits acetylcholine release after blockade of the NK(2) receptor or after
      sensory nerve depletion with capsaicin. This suggests that NO and endogenous
      tachykinins act in series to produce an increase in acetylcholine release.

PMID- 10960075
TI  - The p38 MAP kinase inhibitor SB203580 enhances nuclear factor-kappa B
      transcriptional activity by a non-specific effect upon the ERK pathway.
AB  - In the present study we investigated a possible role for the p38 mitogen
      activated protein (MAP) kinase pathway in mediating nuclear factor-kappa B (NF
      kappaB) transcriptional activity in the erythroleukaemic cell line TF-1. TF-1
      cells stimulated with the phosphatase inhibitor okadaic acid (OA) demonstrated
      enhanced NF-kappaB and GAL4p65-regulated transcriptional activity which was
      associated with elevated p38 phosphorylation. However, pretreatment with the p38
      MAPK specific inhibitor SB203580 (1 microM) or overexpression of kinase-deficient
      mutants of MKK3 or MKK6 did not affect OA-enhanced NF-kappaB transcriptional
      potency, as determined in transient transfection assays. In fact, 5 and 10 microM
      SB203580 enhanced rather than inhibited NF-kappaB-mediated promoter activity by 2
      fold, which was independent of phosphorylation of the p65 subunit. The SB203580
      mediated increase in NF-kappaB transcriptional activity was associated with
      enhanced phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c
      Jun N-terminal kinase (JNK), but not p38 kinase. Overexpression of kinase
      deficient mutants belonging to the ERK1/2, JNK, and p38 pathways showed that only
      dominant-negative Raf-1 abrogated SB203580-enhanced NF-kappaB activity. This
      would implicate the involvement of the ERK1/2 pathway in the enhancing effects of
      SB203580 on NF-kappaB-mediated gene transcription. This study demonstrates that
      the p38 MAP kinase pathway is not involved in the OA-induced activation of NF
      kappaB. SB203580 at higher concentrations activates the ERK pathway, which
      subsequently enhances NF-kappaB transcriptional activity.

PMID- 10960077
TI  - Mechanisms of the thapsigargin-induced Ca(2+) entry in in situ endothelial cells
      of the porcine aortic valve and the endothelium-dependent relaxation in the
      porcine coronary artery.
AB  - The mechanisms of the thapsigargin (TG)-induced capacitative Ca(2+) entry in in
      situ endothelial cells and its role in the regulation of arterial tone were
      investigated using front-surface fluorimetry and fura-2-loaded strips of porcine
      aortic valve and coronary artery. In the presence of extracellular Ca(2+), TG
      induced an initial rapid and a subsequent sustained elevation of cytosolic Ca(2+)
      concentration ([Ca(2+)](i)) in valvular strips. In the absence of extracellular
      Ca(2+), TG induced only a transient increase in [Ca(2+)](i). The TG-induced
      sustained elevation of [Ca(2+)](i) in endothelial cells was inhibited completely
      by 1 mM Ni(2+) and partly by 10 microM econazole and 30 microM ML-9, but not by
      900 ng ml(-1) pertussis toxin or 100 microM wortmannin. Therefore, cytochrome
      P450 and protein phosphorylation are suggested to be involved in the TG-induced
      Ca(2+) influx in in situ endothelial cells. TG induced an endothelium-dependent
      large relaxation consisting of an initial and a late sustained relaxation in
      coronary arterial strip precontracted with U46619 (a thromboxane A2 analogue).
      Indomethacin alone had no effect, while indomethacin plus N(omega)-nitro-L
      arginine (L-NOARG) markedly inhibited the sustained phase and slightly inhibited
      the initial phase of the TG-induced relaxation. TG induced a smaller but
      sustained relaxation during the 40 mM K(+)-induced precontraction than that seen
      during the U46619-induced precontraction. This relaxation was completely
      abolished by the pretreatment with indomethacin plus L-NOARG. In conclusion, both
      nitric oxide (NO) and endothelium-derived hyperpolarizing factor were suggested
      to mediate the TG-induced relaxation, while NO plays a major role in the
      sustained relaxation. The TG-induced sustained [Ca(2+)](i) elevation in
      endothelial cells was thus suggested to be mainly linked to the sustained
      production of NO.

PMID- 10960076
TI  - ADP is not an agonist at P2X(1) receptors: evidence for separate receptors
      stimulated by ATP and ADP on human platelets.
AB  - ADP, an important agonist in thrombosis and haemostasis, has been reported to
      activate platelets via three receptors, P2X(1), P2Y(1) and P2T(AC). Given the low
      potency of ADP at P2X(1) receptors and recognized contamination of commercial
      samples of adenosine nucleotides, we have re-examined the activation of P2X(1)
      receptors by ADP following HPLC and enzymatic purification. Native P2X(1)
      receptor currents in megakaryocytes were activated by alpha, beta-meATP (10
      microM) and commercial samples of ADP (10 microM), but not by purified ADP (10 -
      100 microM). Purified ADP (up to 1 mM) was also inactive at recombinant human
      P2X(1) receptors expressed in Xenopus oocytes. Purification did not modify the
      ability of ADP to activate P2Y receptors coupled to Ca(2+) mobilization in rat
      megakaryocytes. In human platelets, P2X(1) and P2Y receptor-mediated [Ca(2+)](i)
      responses were distinguished by their different kinetics at 13 degrees C. In 1 mM
      Ca(2+) saline, alpha,beta-meATP (10 microM) and commercial ADP (40 microM)
      activated a rapid [Ca(2+)](i) increase (lag time < or =0.5 s) through the
      activation of P2X(1) receptors. Hexokinase treatment of ADP shifted the lag time
      by approximately 2 s, indicating loss of the P2X(1) receptor-mediated response. A
      revised scheme is proposed for physiological activation of P2 receptors in human
      platelets. ATP stimulates P2X(1) receptors, whereas ADP is a selective agonist at
      metabotropic (P2Y(1) and P2T(AC)) receptors.

PMID- 10960078
TI  - Non-competitive antagonism of beta(2)-agonist-mediated cyclic AMP accumulation by
      ICI 118551 in BC3H1 cells endogenously expressing constitutively active beta(2)
      adrenoceptors.
AB  - Constitutive activity of the beta(2)-adrenoceptor, which is sensitive to
      inhibition by an inverse agonist such as ICI 118551, has been readily
      demonstrated in recombinant systems expressing constitutively-active mutant
      receptors or over-expressing the wild-type beta(2)-adrenoceptor. Here we
      demonstrate the presence of constitutive beta(2)-adrenoceptor activity in BC3H1
      cells which endogenously express this receptor. In BC3H1 cells, only ICI 118551
      behaved as an inverse agonist at beta(2)-adrenoceptors, while propranolol, ICI
      118551, atenolol and, to a lesser extent, alprenolol exhibited inverse agonism in
      CHO-beta(2)4 cells transfected with cDNA for the human beta(2)-adrenoceptor (310
      fmol. mg protein(-1)). The level of expression of beta2-adrenoceptors in BC3H1
      cells was not high (78 fmol.mg protein-1) and the efficiency of receptor -
      effector coupling in this cell line was much lower than in the recombinant CHO
      beta(2)4 cells (as judged by the partial agonist nature of both salbutamol and
      clenbuterol). ICI 118551 (log K(D)-9.73+/-0.07) and propranolol (log K(D)-9.25+/
      0.12) both behaved as conventional competitive antagonists of isoprenaline
      stimulated cyclic AMP accumulation in high expressing CHO-beta(2)4 cells. In
      contrast, ICI 118551 appeared to act as a non-competitive antagonist in BC3H1
      cells and in low expressing CHO-beta(2)6 cells (50 fmol.mg protein(-1)). This non
      competitive effect of ICI 118551 in BC3H1 cells was also observed when either
      salbutamol was used as agonist, or the incubation period with isoprenaline was
      extended to 30 min. The possibility that these effects of ICI 118551 are due to
      an interaction with different affinity states (R, R* and R') of the receptor is
      discussed.

PMID- 10960079
TI  - Endogenously produced nitric oxide inhibits endothelial cell growth as
      demonstrated using novel antisense cell lines.
AB  - Proliferation of endothelial cells is a vital component of vascular repair and
      angiogenesis. The endothelial cell mediator, nitric oxide (NO) has been reported
      both to inhibit and to promote endothelial cell proliferation. In this study we
      have generated cell lines which constitutively express antisense RNA to a region
      of inducible nitric oxide synthase (iNOS) from a murine endothelial cell line,
      sEnd-1. In response to stimulation with lipopolysaccharide (LPS) and interferon
      gamma (IFN-gamma) these antisense cells had no detectable RNA for endogenous
      iNOS, barely detectable iNOS protein and produced 82% less NO than did the
      control transfected line. Stimulation of the control transfected line caused
      significant NO production and inhibition of cell growth whereas for the antisense
      line, producing little NO in response to stimulation, proliferation remained the
      same as for unstimulated cells. No differences in cell death were observed
      between unstimulated and LPS/IFN-gamma stimulated cells. The data presented in
      this study directly demonstrate that NO derived endogenously from iNOS inhibits
      proliferation of endothelial cells. This approach overcomes problems in other
      studies where NO donors or non-isoform specific inhibitors of NO synthase have
      been used.

PMID- 10960081
TI  - Formation of 8-iso-PGF(2alpha) and thromboxane A(2) by stimulation with several
      activators of phospholipase A(2) in the isolated human umbilical vein.
AB  - We investigated the effects of the phospholipase A(2) (PLA(2)) activators calcium
      ionophore A 23187, hydrogen peroxide (H(2)O(2)), bradykinin (BK), histamine and
      noradrenaline (NA) on the 8-iso-prostaglandin (PG)F(2alpha) formation in the
      isolated human umbilical vein and the isolated rabbit ear. For comparison, the
      influence of these substances on the thromboxane A(2) (TXA(2)) release was also
      investigated. The release of total (esterified as well as free) 8-iso
      PGF(2alpha), free 8-iso-PGF(2alpha) and TXB(2), the stable metabolite of TXA(2),
      was determined by specific enzyme immunoassays. The results show that bolus
      injections of 5.4 mmol H(2)O(2), 30 nmol A 23187, 10 nmol BK, 50 nmol histamine
      and 20 nmol NA caused an increased release of total 8-iso-PGF(2alpha) in the
      umbilical vein and the rabbit ear. A perfusion with H(2)O(2) at a final
      concentration of 0.3 mM also increased the release of this isoprostane. Increased
      formation of free 8-iso-PGF(2alpha) was induced by A 23187 injection and by both
      modes of H(2)O(2) administration, but not by the other treatments. Bolus
      injections of A 23187, BK and histamine induced an increased release of TXB(2) in
      both organs. Both modes of H(2)O(2) administration and NA showed no releasing
      effects. In conclusion, our results show that the substances used are able to
      stimulate the formation of 8-iso-PGF(2alpha) concurrently with the release of
      PGs. This effect might be of pathophysiological relevance in inflammatory and
      cardiovascular diseases in which an enhanced release of free radicals, BK,
      histamine or NA play an important role.

PMID- 10960083
TI  - Corrigendum

PMID- 10960080
TI  - Enhanced reduction of myocardial infarct size by combined ACE inhibition and
      AT(1)-receptor antagonism.
AB  - The effects of the angiotensin-converting-enzyme inhibitor (ACEI) ramiprilat, the
      angiotensin II type 1 receptor antagonist (AT(1)A) candesartan, and the
      combination of both drugs on infarct size (IS) resulting from regional myocardial
      ischaemia were studied in pigs. Both ACEI and AT(1)A reduce myocardial IS by a
      bradykinin-mediated process. It is unclear, however, whether the combination of
      ACEI and AT(1)A produces a more pronounced IS reduction than each of these drugs
      alone. Forty-six enflurane-anaesthetized pigs underwent 90 min low-flow ischaemia
      and 120 min reperfusion. Systemic haemodynamics (micromanometer), subendocardial
      blood flow (ENDO, microspheres) and IS (TTC-staining) were determined. The
      decreases in left ventricular peak pressure by ACEI (by 9+/-2 (s.e. mean) mmHg),
      AT(1)A (by 11+/-2 mmHg) or their combination (by 18+/-3 mmHg, P<0.05 vs ACEI and
      AT(1)A, respectively) were readjusted by aortic constriction prior to ischaemia.
      With placebo (n=10), IS averaged 20.0+/-3.3% of the area at risk. IS was reduced
      to 9.8+/-2.6% with ramiprilat (n=10) and 10.6+/-3.1% with candesartan (n=10).
      Combined ramiprilat and candesartan (n=10) reduced IS to 6.7+/-2.1%. Blockade of
      the bradykinin-B(2)-receptor with icatibant prior to ACEI and AT(1)A completely
      abolished the reduction of IS (n=6, 22.8+/-6.1%). The relationship between IS and
      ischaemic ENDO with placebo was shifted downwards by each ACEI and AT(1)A and
      further shifted downwards with their combination (P<0.05 vs all groups);
      icatibant again abolished such downward shift. The combination of ACEI and AT(1)A
      enhances the reduction of IS following ischaemia/reperfusion compared to a
      monotherapy by either drug alone; this effect is mediated by bradykinin.

PMID- 10960082
TI  - Induction of COX-2 and PGE(2) biosynthesis by IL-1beta is mediated by PKC and
      mitogen-activated protein kinases in murine astrocytes.
AB  - Interleukin-1 (IL-1) is an important mediator of immunoinflammatory responses in
      the brain. In the present study, we examined whether prostaglandin E(2) (PGE(2))
      production after IL-1beta stimulation is dependent upon activation of protein
      kinases in astroglial cells. Astrocyte cultures stimulated with IL-1beta or the
      phorbol ester, PMA significantly increased PGE(2) secretion. The stimulatory
      action of IL-1beta on PGE(2) production was totally abolished by NS-398, a
      specific inhibitor of cyclo-oxygenase-2 activity, as well as by the protein
      synthesis inhibitor cycloheximide, and the glucocorticoid dexamethasone.
      Furthermore, IL-1beta induced the expression of COX-2 mRNA. This occurred early
      at 2 h, with a maximum at 4 h and declined at 12 h. IL-1 beta treatment also
      induced the expression of COX-2 protein as determined by immunoblot analysis. In
      that case the expression of the protein remained high at least up to 12 h.
      Treatment of cells with protein kinase C inhibitors (H-7, bisindolylmaleimide and
      calphostin C) inhibited IL-1beta stimulation of PGE(2). In addition, PKC-depleted
      astrocyte cultures by overnight treatment with PMA no longer responded to PMA or
      IL-1. The ablation of the effects of PMA and IL-1beta on PGE(2) production,
      likely results from down-regulation of phorbol ester sensitive-PKC isoenzymes.
      Immunoblot analysis demonstrated the translocation of the conventional isoform
      cPKC-alpha from cytosol to membrane following treatment with IL-1beta. In
      addition, IL-1beta treatment led to activation of extracellular signal-regulated
      kinase (ERK1/2) and p38 subgroups of MAP kinases in astroglial cells.
      Interestingly, the inhibition of ERK kinase with PD 98059, as well as the
      inhibition of p38 MAPK with SB 203580, prevented IL-1beta-induced PGE(2) release.
      ERK1/2 activation by IL-1beta was sensitive to inhibition by the PKC inhibitor
      bisindolylmaleimide suggesting that ERK phosphorylation is a downstream signal of
      PKC activation. These results suggest key roles for PKC as well as for ERK1/2 and
      p38 MAP kinase cascades in the biosynthesis of PGE(2), likely by regulating the
      induction of cyclo-oxygenase-2, in IL-1beta-stimulated astroglial cells.

PMID- 10960084
TI  - Vectorial metabolism and the evolution of transport systems.

PMID- 10960085
TI  - Characterization of the operon encoding the alternative sigma(B) factor from
      Bacillus anthracis and its role in virulence.
AB  - The operon encoding the general stress transcription factor sigma(B) and two
      proteins of its regulatory network, RsbV and RsbW, was cloned from the gram
      positive bacterium Bacillus anthracis by PCR amplification of chromosomal DNA
      with degenerate primers, by inverse PCR, and by direct cloning. The gene cluster
      was very similar to the Bacillus subtilis sigB operon both in the primary
      sequences of the gene products and in the order of its three genes. However, the
      deduced products of sequences upstream and downstream from this operon showed no
      similarity to other proteins encoded by the B. subtilis sigB operon. Therefore,
      the B. anthracis sigB operon contains three genes rather than eight as in B.
      subtilis. The B. anthracis operon is preceded by a sigma(B)-like promoter
      sequence, the expression of which depends on an intact sigma(B) transcription
      factor in B. subtilis. It is followed by another open reading frame that is also
      preceded by a promoter sequence similarly dependent on B. subtilis sigma(B). We
      found that in B. anthracis, both these promoters were induced during the
      stationary phase and induction required an intact sigB gene. The sigB operon was
      induced by heat shock. Mutants from which sigB was deleted were constructed in a
      toxinogenic and a plasmidless strain. These mutants differed from the parental
      strains in terms of morphology. The toxinogenic sigB mutant strain was also less
      virulent than the parental strain in the mouse model. B. anthracis sigma(B) may
      therefore be a minor virulence factor.

PMID- 10960087
TI  - Regulation of transcription of the mph(A) gene for macrolide 2'
      phosphotransferase I in Escherichia coli: characterization of the regulatory gene
      mphR(A).
AB  - The synthesis of macrolide 2'-phosphotransferase I [Mph(A)], which inactivates
      erythromycin, is inducible by erythromycin. The expression of high-level
      resistance to erythromycin requires the mph(A) and mrx genes, which encode Mph(A)
      and an unidentified protein, respectively. We have studied the mphR(A) gene,
      which regulates the inducible expression of mph(A). An analysis of the synthesis
      of Mph(A) in minicells and results of a complementation test indicated that
      mphR(A) is located downstream from mrx and that its product, MphR(A), represses
      the production of Mph(A). DNA sequencing indicated that the mph(A), mrx, and
      mphR(A) genes exist as a cluster that begins with mph(A) and that the deduced
      amino acid sequence of MphR(A) can adopt an alpha-helix-turn-alpha-helix
      structure. To study the regulation of gene expression by MphR(A), we performed
      Northern blotting and primer extension. A transcript of 2. 9 kb that corresponded
      to the transcript of mph(A) through mphR(A) was detected, and its level was
      elevated upon exposure of cells to erythromycin. Gel mobility shift assays and
      DNase I footprinting indicated that MphR(A) binds specifically to the promoter
      region of mph(A), and the amount of DNA shifted as a results of the binding of
      MphR(A) decreased as the concentration of erythromycin was increased. These
      results indicate that transcription of the mph(A)-mrx-mphR(A) operon is
      negatively regulated by the binding of a repressor protein, MphR(A), to the
      promoter of the mph(A) gene and is activated upon inhibition of binding of
      MphR(A) to the promoter in the presence of erythromycin.

PMID- 10960086
TI  - A hydrogen peroxide-forming NADH oxidase that functions as an alkyl hydroperoxide
      reductase in Amphibacillus xylanus.
AB  - The Amphibacillus xylanus NADH oxidase, which catalyzes the reduction of oxygen
      to hydrogen peroxide with beta-NADH, can also reduce hydrogen peroxide to water
      in the presence of free flavin adenine dinucleotide (FAD) or the small disulfide
      containing Salmonella enterica AhpC protein. The enzyme has two disulfide bonds,
      Cys128-Cys131 and Cys337-Cys340, which can act as redox centers in addition to
      the enzyme-bound FAD (K. Ohnishi, Y. Niimura, M. Hidaka, H. Masaki, H. Suzuki, T.
      Uozumi, and T. Nishino, J. Biol. Chem. 270:5812-5817, 1995). The NADH-FAD
      reductase activity was directly dependent on the FAD concentration, with a second
      order rate constant of approximately 2.0 x 10(6) M(-1) s(-1). Rapid-reaction
      studies showed that the reduction of free flavin occurred through enzyme-bound
      FAD, which was reduced by NADH. The peroxidase activity of NADH oxidase in the
      presence of FAD resulted from reduction of peroxide by free FADH(2) reduced via
      enzyme-bound FAD. This peroxidase activity was markedly decreased in the presence
      of oxygen, since the free FADH(2) is easily oxidized by oxygen, indicating that
      this enzyme system is unlikely to be functional in aerobic growing cells. The A.
      xylanus ahpC gene was cloned and overexpressed in Escherichia coli. When the NADH
      oxidase was coupled with A. xylanus AhpC, the peroxidase activity was not
      inhibited by oxygen. The V(max) values for hydrogen peroxide and cumene
      hydroperoxide reduction were both approximately 150 s(-1). The K(m) values for
      hydrogen peroxide and cumene hydroperoxide were too low to allow accurate
      determination of their values. Both AhpC and NADH oxidase were induced under
      aerobic conditions, a clear indication that these proteins are involved in the
      removal of peroxides under aerobic growing conditions.

PMID- 10960089
TI  - Recovery of hydrogen peroxide-sensitive culturable cells of Vibrio vulnificus
      gives the appearance of resuscitation from a viable but nonculturable state.
AB  - The viabilities of five strains of Vibrio vulnificus were evaluated during the
      storage of the organisms in sterile seawater at 5 degrees C. The number of CFU
      was measured by plate count methods on rich media. The total cell numbers were
      determined by direct microscopic count methods. The titer of CFU declined
      logarithmically to undetectable levels over a period of 2 to 3 weeks, while the
      total cell numbers were unchanged. Midway through each study, higher culturable
      cell counts began to be observed on plates containing catalase or sodium
      pyruvate; during the latter stages of the study, the plate counts on such media
      were up to 1,000-fold higher than those on unsupplemented plates. Because
      autoclaving is known to generate hydrogen peroxide in rich media, and because
      catalase and sodium pyruvate are known to eliminate hydrogen peroxide, it appears
      that the conditions of the experiments led to the selection of a hydrogen
      peroxide-sensitive culturable cell subpopulation. At the time of the final stage
      of the decline in viability of each culture, hydrogen peroxide-sensitive cells
      were the only culturable cells present. Warming samples of the cultures to room
      temperature led to the growth of these residual culturable cells, utilizing
      nutrients provided by the nonculturable cells. The cells that grew recovered
      hydrogen peroxide resistance. When mixtures of culturable and nonculturable cells
      were diluted to the point where only nonculturable cells were present, or when
      the hydrogen peroxide-sensitive culturable cells had declined to undetectable
      levels, warming had no effect; no culturable cells were recovered. Warming has
      been reported to "resuscitate" nonculturable cells. Recognition of the existence
      of hydrogen peroxide-sensitive culturable cell populations, as well as their
      ability to grow to high levels in the warmed seawater microcosms, leads instead
      to the conclusion that while warming permits culturable cells to grow, it has no
      effect on nonculturable cells.

PMID- 10960088
TI  - The redox-sensitive transcriptional activator OxyR regulates the peroxide
      response regulon in the obligate anaerobe Bacteroides fragilis.
AB  - The peroxide response-inducible genes ahpCF, dps, and katB in the obligate
      anaerobe Bacteroides fragilis are controlled by the redox-sensitive
      transcriptional activator OxyR. This is the first functional oxidative stress
      regulator identified and characterized in anaerobic bacteria. oxyR and dps were
      found to be divergently transcribed, with an overlap in their respective promoter
      regulatory regions. B. fragilis OxyR and Dps proteins showed high identity to
      homologues from a closely related anaerobe, Porphyromonas gingivalis. Northern
      blot analysis revealed that oxyR was expressed as a monocistronic 1-kb mRNA and
      that dps mRNA was approximately 500 bases in length. dps mRNA was induced over
      500-fold by oxidative stress in the parent strain and was constitutively induced
      in the peroxide-resistant mutant IB263. The constitutive peroxide response in
      strain IB263 was shown to have resulted from a missense mutation at codon 202
      (GAT to GGT) of the oxyR gene [oxyR(Con)] with a predicted D202G substitution in
      the OxyR protein. Transcriptional fusion analysis revealed that deletion of oxyR
      abolished the induction of ahpC and katB following treatment with hydrogen
      peroxide or oxygen exposure. However, dps expression was induced approximately
      fourfold by oxygen exposure in DeltaoxyR strains but not by hydrogen peroxide.
      This indicates that dps expression is also under the control of an oxygen
      dependent OxyR-independent mechanism. Complementation of DeltaoxyR mutant strains
      with wild-type oxyR and oxyR(Con) restored the inducible peroxide response and
      the constitutive response of the ahpCF, katB, and dps genes, respectively.
      However, overexpression of OxyR abolished the catalase activity but not katB
      expression, suggesting that higher levels of intracellular OxyR may be involved
      in other physiological processes. Analysis of oxyR expression in the parents and
      in DeltaoxyR and overexpressing oxyR strains by Northern blotting and oxyR'::xylB
      fusions revealed that B. fragilis OxyR does not control its own expression.

PMID- 10960090
TI  - Recognition of overlapping nucleotides by AraC and the sigma subunit of RNA
      polymerase.
AB  - The Escherichia coli promoter p(BAD), under the control of the AraC protein,
      drives the expression of mRNA encoding the AraB, AraA, and AraD gene products of
      the arabinose operon. The binding site of AraC at p(BAD) overlaps the RNA
      polymerase -35 recognition region by 4 bases, leaving 2 bases of the region not
      contacted by AraC. This overlap raises the question of whether AraC substitutes
      for the sigma subunit of RNA polymerase in recognition of the -35 region or
      whether both AraC and sigma make important contacts with the DNA in the -35
      region. If sigma does not contact DNA near the -35 region, p(BAD) activity should
      be independent of the identity of the bases in the hexamer region that are not
      contacted by AraC. We have examined this issue in the p(BAD) promoter and in a
      second promoter where the AraC binding site overlaps the -35 region by only 2
      bases. In both cases promoter activity is sensitive to changes in bases not
      contacted by AraC, showing that despite the overlap, sigma does read DNA in the 
      35 region. Since sigma and AraC are thus closely positioned at p(BAD), it is
      possible that AraC and sigma contact one another during transcription initiation.
      DNA migration retardation assays, however, showed that there exists only a slight
      degree of DNA binding cooperativity between AraC and sigma, thus suggesting
      either that the normal interactions between AraC and sigma are weak or that the
      presence of the entire RNA polymerase is necessary for significant interaction.

PMID- 10960092
TI  - Metronidazole activation is mutagenic and causes DNA fragmentation in
      Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+)
      (Nitroreductase) gene.
AB  - Much of the normal high sensitivity of wild-type Helicobacter pylori to
      metronidazole (Mtz) depends on rdxA (HP0954), a gene encoding a novel
      nitroreductase that catalyzes the conversion of Mtz from a harmless prodrug to a
      bactericidal agent. Here we report that levels of Mtz that partially inhibit
      growth stimulate forward mutation to rifampin resistance in rdxA(+) (Mtz(s)) and
      also in rdxA (Mtz(r)) H. pylori strains, and that expression of rdxA in
      Escherichia coli results in equivalent Mtz-induced mutation. A reversion test
      using defined lac tester strains of E. coli carrying rdxA(+) indicated that CG-to
      GC transversions and AT-to-GC transitions are induced more frequently than other
      base substitutions. Alkaline gel electrophoretic tests showed that Mtz
      concentrations near or higher than the MIC for growth also caused DNA breakage in
      H. pylori and in E. coli carrying rdxA(+), suggesting that this damage may
      account for most of the bactericidal action of Mtz. Coculture of Mtz(s) H. pylori
      with E. coli (highly resistant to Mtz) in the presence of Mtz did not stimulate
      forward mutation in E. coli, indicating that the mutagenic and bactericidal
      products of Mtz metabolism do not diffuse significantly to neighboring
      (bystander) cells. Our results suggest that the widespread use of Mtz against
      other pathogens in people chronically infected with H. pylori may stimulate
      mutation and recombination in H. pylori, thereby speeding host-specific
      adaptation, the evolution of virulence, and the emergence of resistance against
      Mtz and other clinically useful antimicrobials.

PMID- 10960091
TI  - Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes
      causes moderate and high-level metronidazole resistance in Helicobacter pylori.
AB  - Helicobacter pylori is a human-pathogenic bacterial species that is subdivided
      geographically, with different genotypes predominating in different parts of the
      world. Here we test and extend an earlier conclusion that metronidazole (Mtz)
      resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase
      that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA
      genes PCR amplified from 50 representative Mtz(r) strains from previously
      unstudied populations in Asia, South Africa, Europe, and the Americas could, in
      each case, transform Mtz(s) H. pylori to Mtz(r); (ii) Mtz(r) mutant derivatives
      of a cultured Mtz(s) strain resulted from mutation in rdxA; and (iii)
      transformation of Mtz(s) strains with rdxA-null alleles usually resulted in
      moderate level Mtz resistance (16 microg/ml). However, resistance to higher Mtz
      levels was common among clinical isolates, a result that implicates at least one
      additional gene. Expression in Escherichia coli of frxA (HP0642; flavin
      oxidoreductase), an rdxA paralog, made this normally resistant species Mtz(s),
      and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had
      little effect on the Mtz susceptibility of rdxA(+) cells. Strains carrying frxA
      null and rdxA-null alleles could mutate to even higher resistance, a result
      implicating one or more additional genes in residual Mtz susceptibility and
      hyperresistance. We conclude that most Mtz resistance in H. pylori depends on
      rdxA inactivation, that mutations in frxA can enhance resistance, and that genes
      that confer Mtz resistance without rdxA inactivation are rare or nonexistent in
      H. pylori populations.

PMID- 10960093
TI  - Characterization of vibrio cholerae O1 antigen as the bacteriophage K139 receptor
      and identification of IS1004 insertions aborting O1 antigen biosynthesis.
AB  - Bacteriophage K139 was recently characterized as a temperate phage of O1 Vibrio
      cholerae. In this study we have determined the phage adsorption site on the
      bacterial cell surface. Phage-binding studies with purified lipopolysaccharide
      (LPS) of different O1 serotypes and biotypes revealed that the O1 antigen serves
      as the phage receptor. In addition, phage-resistant O1 El Tor strains were
      screened by using a virulent isolate of phage K139. Analysis of the LPS of such
      spontaneous phage-resistant mutants revealed that most of them synthesize
      incomplete LPS molecules, composed of either defective O1 antigen or core
      oligosaccharide. By applying phage-binding studies, it was possible to
      distinguish between receptor mutants and mutations which probably caused abortion
      of later steps of phage infection. Furthermore, we investigated the genetic
      nature of O1-negative strains by Southern hybridization with probes specific for
      the O antigen biosynthesis cluster (rfb region). Two of the investigated O1
      antigen-negative mutants revealed insertions of element IS1004 into the rfb gene
      cluster. Treating one wbeW::IS1004 serum-sensitive mutant with normal human
      serum, we found that several survivors showed precise excision of IS1004,
      restoring O antigen biosynthesis and serum resistance. Investigation of clinical
      isolates by screening for phage resistance and performing LPS analysis of
      nonlysogenic strains led to the identification of a strain with decreased O1
      antigen presentation. This strain had a significant reduction in its ability to
      colonize the mouse small intestine.

PMID- 10960094
TI  - Changes in cspL, cspP, and cspC mRNA abundance as a function of cold shock and
      growth phase in Lactobacillus plantarum.
AB  - An inverse PCR strategy based on degenerate primers has been used to identify new
      genes of the cold shock protein family in Lactobacillus plantarum. In addition to
      the two previously reported cspL and cspP genes, a third gene, cspC, has been
      cloned and characterized. All three genes encode small 66-amino-acid proteins
      with between 73 and 88% identity. Comparative Northern blot analyses showed that
      the level of cspL mRNA increases up to 17-fold after a temperature downshift,
      whereas the mRNA levels of cspC and cspP remain unchanged or increase only
      slightly (about two- to threefold). Cold induction of cspL mRNA is transient and
      delayed in time as a function of the severity of the temperature downshift. The
      cold shock behavior of the three csp mRNAs contrasts with that observed for four
      unrelated non-csp genes, which all showed a sharp decrease in mRNA level,
      followed in one case (bglH) by a progressive recovery of the transcript during
      prolonged cold exposure. Abundance of the three csp mRNAs was also found to vary
      during growth at optimal temperature (28 degrees C). cspC and cspP mRNA levels
      are maximal during the lag period, whereas the abundance of the cspL transcript
      is highest during late-exponential-phase growth. The differential expression of
      the three L. plantarum csp genes can be related to sequence and structural
      differences in their untranslated regions. It also supports the view that the
      gene products fulfill separate and specific functions, under both cold shock and
      non-cold shock conditions.

PMID- 10960095
TI  - Bacteriophage phiYeO3-12, specific for Yersinia enterocolitica serotype O:3, is
      related to coliphages T3 and T7.
AB  - Bacteriophage phiYeO3-12 is a lytic phage of Yersinia enterocolitica serotype
      O:3. The phage receptor is the lipopolysaccharide O chain of this serotype that
      consists of the rare sugar 6-deoxy-L-altropyranose. A one-step growth curve of
      phiYeO3-12 revealed eclipse and latent periods of 15 and 25 min, respectively,
      with a burst size of about 120 PFU per infected cell. In electron microscopy
      phiYeO3-12 virions showed pentagonal outlines, indicating their icosahedral
      nature. The phage capsid was shown to be composed of at least 10 structural
      proteins, of which a protein of 43 kDa was predominant. N-terminal sequences of
      three structural proteins were determined, two of them showing strong homology to
      structural proteins of coliphages T3 and T7. The phage genome was found to
      consist of a double-stranded DNA molecule of 40 kb without cohesive ends. A
      physical map of the phage DNA was constructed using five restriction enzymes. The
      phage infection could be effectively neutralized using serum from a rabbit
      immunized with whole phiYeO3-12 particles. The antiserum also neutralized T3
      infection, although not as efficiently as that of phiYeO3-12. phiYeO3-12 was
      found to share, in addition to the N-terminal sequence homology, several common
      features with T3, including morphology and nonsubjectibility to F exclusion. The
      evidence conclusively indicated that phiYeO3-12 is the first close relative of
      phage T3 to be described.

PMID- 10960096
TI  - Cooperative regulation of DOG2, encoding 2-deoxyglucose-6-phosphate phosphatase,
      by Snf1 kinase and the high-osmolarity glycerol-mitogen-activated protein kinase
      cascade in stress responses of Saccharomyces cerevisiae.
AB  - We screened the genome of Saccharomyces cerevisiae for the genes responsive to
      oxidative stress by using the lacZ transposon-insertion library. As a result, we
      found that expression of the DOG2 gene coding for 2-deoxyglucose-6-phosphate
      phosphatase was induced by oxidative stress. The expression of DOG2 was also
      induced by osmotic stress. We found a putative cis element (STRE, a stress
      response element) in the DOG2 promoter adjacent to a consensus sequence to which
      the Mig1p repressor is known to bind. The basal levels of DOG2 gene expression
      were increased in a mig1Delta mutant, while the derepression of DOG2 was not
      observed in a snf1Delta mutant under glucose-deprived conditions. Induction of
      the DOG2 gene expression by osmotic stress was observed in any of the three
      disruptants pbs2Delta, hog1Delta, and snf1Delta. However, the osmotic induction
      was completely abolished in both the snf1Delta pbs2Delta mutant and the snf1Delta
      hog1Delta mutant. Additionally, these single mutants as well as double mutants
      failed to induce DOG2 expression by oxidative stress. These results suggest that
      Snf1p kinase and the high-osmolarity glycerol-mitogen-activated protein kinase
      cascade are likely to be involved in the signaling pathway of oxidative stress
      and osmotic stress in regulation of DOG2.

PMID- 10960097
TI  - Plasmid-located pathogenicity determinants of Serratia entomophila, the causal
      agent of amber disease of grass grub, show similarity to the insecticidal toxins
      of Photorhabdus luminescens.
AB  - Serratia entomophila and Serratia proteamaculans cause amber disease in the grass
      grub Costelytra zealandica (Coleoptera: Scarabaeidae), an important pasture pest
      in New Zealand. Larval disease symptoms include cessation of feeding, clearance
      of the gut, amber coloration, and eventual death. A 115-kb plasmid, pADAP,
      identified in S. entomophila is required for disease causation and, when
      introduced into Escherichia coli, enables that organism to cause amber disease. A
      23-kb fragment of pADAP that conferred disease-causing ability on E. coli and a
      pADAP-cured strain of S. entomophila was isolated. Using insertion mutagenesis,
      the pathogenicity determinants were mapped to a 17-kb region of the clone.
      Sequence analysis of the 17-kb region showed that the predicted products of three
      of the open reading frames (sepA, sepB, and sepC) showed significant sequence
      similarity to components of the insecticidal toxin produced by the bacterium
      Photorhabdus luminescens. Transposon insertions in sepA, sepB, or sepC completely
      abolished both gut clearance and cessation of feeding on the 23-kb clone; when
      recombined back into pADAP, they abolished gut clearance but not cessation of
      feeding. These results suggest that SepA, SepB, and SepC together are sufficient
      for amber disease causation by S. entomophila and that another locus also able to
      exert a cessation-of-feeding effect is encoded elsewhere on pADAP.

PMID- 10960098
TI  - Identification of Escherichia coli ubiB, a gene required for the first
      monooxygenase step in ubiquinone biosynthesis.
AB  - It was recently discovered that the aarF gene in Providencia stuartii is required
      for coenzyme Q (CoQ) biosynthesis. Here we report that yigR, the Escherichia coli
      homologue of aarF, is ubiB, a gene required for the first monooxygenase step in
      CoQ biosynthesis. Both the P. stuartii aarF and E. coli ubiB (yigR) disruption
      mutant strains lack CoQ and accumulate octaprenylphenol. Octaprenylphenol is the
      CoQ biosynthetic intermediate found to accumulate in the E. coli strain AN59,
      which contains the ubiB409 mutant allele. Analysis of the mutation in the E. coli
      strain AN59 reveals no mutations within the ubiB gene, but instead shows the
      presence of an IS1 element at position +516 of the ubiE gene. The ubiE gene
      encodes a C-methyltransferase required for the synthesis of both CoQ and
      menaquinone, and it is the 5' gene in an operon containing ubiE, yigP, and ubiB.
      The data indicate that octaprenylphenol accumulates in AN59 as a result of a
      polar effect of the ubiE::IS1 mutation on the downstream ubiB gene. AN59 is
      complemented by a DNA segment containing the contiguous ubiE, yigP, and ubiB
      genes. Although transformation of AN59 with a DNA segment containing the ubiB
      coding region fails to restore CoQ biosynthesis, transformation with the ubiE
      coding region results in a low-frequency but significant rescue attributed to
      homologous recombination. In addition, the fre gene, previously considered to
      correspond to ubiB, was found not to be involved in CoQ biosynthesis. The ubiB
      gene is a member of a predicted protein kinase family of which the Saccharomyces
      cerevisiae ABC1 gene is the prototypic member. The possible protein kinase
      function of UbiB and Abc1 and the role these polypeptides may play in CoQ
      biosynthesis are discussed.

PMID- 10960099
TI  - Essentiality, expression, and characterization of the class II 3-hydroxy-3
      methylglutaryl coenzyme A reductase of Staphylococcus aureus.
AB  - Sequence comparisons have implied the presence of genes encoding enzymes of the
      mevalonate pathway for isopentenyl diphosphate biosynthesis in the gram-positive
      pathogen Staphylococcus aureus. In this study we showed through genetic
      disruption experiments that mvaA, which encodes a putative class II 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, is essential for in vitro growth
      of S. aureus. Supplementation of media with mevalonate permitted isolation of an
      auxotrophic mvaA null mutant that was attenuated for virulence in a murine
      hematogenous pyelonephritis infection model. The mvaA gene was cloned from S.
      aureus DNA and expressed with an N-terminal His tag in Escherichia coli. The
      encoded protein was affinity purified to apparent homogeneity and was shown to be
      a class II HMG-CoA reductase, the first class II eubacterial biosynthetic enzyme
      isolated. Unlike most other HMG-CoA reductases, the S. aureus enzyme exhibits
      dual coenzyme specificity for NADP(H) and NAD(H), but NADP(H) was the preferred
      coenzyme. Kinetic parameters were determined for all substrates for all four
      catalyzed reactions using either NADP(H) or NAD(H). In all instances optimal
      activity using NAD(H) occurred at a pH one to two units more acidic than that
      using NADP(H). pH profiles suggested that His378 and Lys263, the apparent
      cognates of the active-site histidine and lysine of Pseudomonas mevalonii HMG-CoA
      reductase, function in catalysis and that the general catalytic mechanism is
      valid for the S. aureus enzyme. Fluvastatin inhibited competitively with HMG-CoA,
      with a K(i) of 320 microM, over 10(4) higher than that for a class I HMG-CoA
      reductase. Bacterial class II HMG-CoA reductases thus are potential targets for
      antibacterial agents directed against multidrug-resistant gram-positive cocci.

PMID- 10960101
TI  - A positive cis-acting DNA element is required for high-level transcription in
      Chlamydia.
AB  - The spacer A/T region is a positive cis-acting DNA element that was identified in
      the Chlamydia trachomatis rRNA promoter region. We have now demonstrated that
      similar sequences in other chlamydial promoters are important for transcription.
      Substitution of candidate spacer A/T regions in four chlamydial promoters
      decreased transcription by partially purified C. trachomatis RNA polymerase in an
      in vitro transcription assay. Addition of a spacer A/T region to the dnaK
      promoter, which does not contain an identifiable spacer A/T region, increased
      transcription 16-fold. Transcription of Escherichia coli promoters by C.
      trachomatis RNA polymerase also appeared to be dependent on the spacer A/T
      region. However, the effect of the spacer A/T region on transcription by E. coli
      RNA polymerase was small. In summary, the spacer A/T region is a novel DNA
      element that is required for high-level transcription of many promoters by
      chlamydial RNA polymerase.

PMID- 10960100
TI  - ZipA-induced bundling of FtsZ polymers mediated by an interaction between C
      terminal domains.
AB  - FtsZ and ZipA are essential components of the septal ring apparatus, which
      mediates cell division in Escherichia coli. FtsZ is a cytoplasmic tubulin-like
      GTPase that forms protofilament-like homopolymers in vitro. In the cell, the
      protein assembles into a ring structure at the prospective division site early in
      the division cycle, and this marks the first recognized event in the assembly of
      the septal ring. ZipA is an inner membrane protein which is recruited to the
      nascent septal ring at a very early stage through a direct interaction with FtsZ.
      Using affinity blotting and protein localization techniques, we have determined
      which domain on each protein is both sufficient and required for the interaction
      between the two proteins in vitro as well as in vivo. The results show that ZipA
      binds to residues confined to the 20 C-terminal amino acids of FtsZ. The FtsZ
      binding (FZB) domain of ZipA is significantly larger and encompasses the C
      terminal 143 residues of ZipA. Significantly, we find that the FZB domain of ZipA
      is also required and sufficient to induce dramatic bundling of FtsZ
      protofilaments in vitro. Consistent with the notion that the ability to bind and
      bundle FtsZ polymers is essential to the function of ZipA, we find that ZipA
      derivatives lacking an intact FZB domain fail to support cell division in cells
      depleted for the native protein. Interestingly, ZipA derivatives which do contain
      an intact FZB domain but which lack the N-terminal membrane anchor or in which
      this anchor is replaced with the heterologous anchor of the DjlA protein also
      fail to rescue ZipA(-) cells. Thus, in addition to the C-terminal FZB domain, the
      N-terminal domain of ZipA is required for ZipA function. Furthermore, the
      essential properties of the N domain may be more specific than merely acting as a
      membrane anchor.

PMID- 10960102
TI  - Cloning and characterization of the glucooligosaccharide catabolic pathway beta
      glucan glucohydrolase and cellobiose phosphorylase in the marine hyperthermophile
      Thermotoga neapolitana.
AB  - Characterization in Thermotoga neapolitana of a catabolic gene cluster encoding
      two glycosyl hydrolases, 1,4-beta-D-glucan glucohydrolase (GghA) and cellobiose
      phosphorylase (CbpA), and the apparent absence of a cellobiohydrolase (Cbh)
      suggest a nonconventional pathway for glucan utilization in Thermotogales. GghA
      purified from T. neapolitana is a 52.5-kDa family 1 glycosyl hydrolase with
      optimal activity at pH 6.5 and 95 degrees C. GghA releases glucose from soluble
      glucooligomers, with a preference for longer oligomers: k(cat)/K(m) values are
      155.2, 76.0, and 9.9 mM(-1) s(-1) for cellotetraose, cellotriose, and cellobiose,
      respectively. GghA has broad substrate specificity, with specific activities of
      236 U/mg towards cellobiose and 251 U/mg towards lactose. With p-nitrophenyl-beta
      glucoside as the substrate, GghA exhibits biphasic kinetic behavior, involving
      both substrate- and end product-directed activation. Its capacity for
      transglycosylation is a factor in this activation. Cloning of gghA revealed a
      contiguous upstream gene (cbpA) encoding a 93.5-kDa cellobiose phosphorylase.
      Recombinant CbpA has optimal activity at pH 5.0 and 85 degrees C. It has specific
      activity of 11.8 U/mg and a K(m) of 1.42 mM for cellobiose, but shows no activity
      towards other disaccharides or cellotriose. With its single substrate specificity
      and low K(m) for cellobiose (compared to GghA's K(m) of 28.6 mM), CbpA may be the
      primary enzyme for attacking cellobiose in Thermotoga spp. By phosphorolysis of
      cellobiose, CbpA releases one activated glucosyl molecule while conserving one
      ATP molecule per disaccharide. CbpA is the first hyperthermophilic cellobiose
      phosphorylase to be characterized.

PMID- 10960103
TI  - Lesions in gshA (Encoding gamma-L-glutamyl-L-cysteine synthetase) prevent aerobic
      synthesis of thiamine in Salmonella enterica serovar typhimurium LT2.
AB  - Thiamine pyrophosphate is an essential cofactor that is synthesized de novo in
      Salmonella enterica serovar Typhimurium and other bacteria. In addition to genes
      encoding enzymes in the biosynthetic pathway, mutations in other metabolic loci
      have been shown to prevent thiamine synthesis. The latter loci identify the
      integration of the thiamine biosynthetic pathway with other metabolic processes
      and can be uncovered when thiamine biosynthesis is challenged. Mutations in gshA,
      encoding gamma-L-glutamyl-L-cysteine synthetase, prevent the synthesis of
      glutathione, the major free thiol in the cell, and are shown here to result in a
      thiamine auxotrophy in some of the strains tested, including S. enterica LT2.
      Phenotypic characterization of the gshA mutants indicated they were similar
      enough to apbC and apbE mutants to warrant the definition of a class of mutants
      unified by (i) a requirement for both the hydroxymethyl pyrimidine (HMP) and
      thiazole (THZ) moiety of thiamine, (ii) the ability of L-tryosine to satisfy the
      THZ requirement, (iii) suppression of the thiamine requirement by anaerobic
      growth, and (iv) suppression by a second-site mutation at a single locus. Genetic
      data indicated that a defective ThiH generates the THZ requirement in these
      strains, and we suggest this defect is due to a reduced ability to repair a
      critical [Fe-S] cluster.

PMID- 10960104
TI  - Phosphorylation-induced signal propagation in the response regulator ntrC.
AB  - The bacterial enhancer-binding protein NtrC is a well-studied response regulator
      in a two-component regulatory system. The amino (N)-terminal receiver domain of
      NtrC modulates the function of its adjacent output domain, which activates
      transcription by the sigma(54) holoenzyme. When a specific aspartate residue in
      the receiver domain of NtrC is phosphorylated, the dimeric protein forms an
      oligomer that is capable of ATP hydrolysis and transcriptional activation. A
      chemical protein cleavage method was used to investigate signal propagation from
      the phosphorylated receiver domain of NtrC, which acts positively, to its central
      output domain. The iron chelate reagent Fe-BABE was conjugated onto unique
      cysteines introduced into the N-terminal domain of NtrC, and the conjugated
      proteins were subjected to Fe-dependent cleavage with or without prior
      phosphorylation. Phosphorylation-dependent cleavage, which requires proximity and
      an appropriate orientation of the peptide backbone to the tethered Fe-EDTA, was
      particularly prominent with conjugated NtrC(D86C), in which the unique cysteine
      lies near the top of alpha-helix 4. Cleavage occurred outside the receiver domain
      itself and on the partner subunit of the derivatized monomer in an NtrC dimer.
      The results are commensurate with the hypothesis that alpha-helix 4 of the
      phosphorylated receiver domain of NtrC interacts with the beginning of the
      central domain for signal propagation. They imply that the phosphorylation
      dependent interdomain and intermolecular interactions between the receiver domain
      of one subunit and the output domain of its partner subunit in an NtrC dimer
      precede-and may give rise to-the oligomerization needed for transcriptional
      activation.

PMID- 10960105
TI  - Cholate resistance in Lactococcus lactis is mediated by an ATP-dependent
      multispecific organic anion transporter.
AB  - The cholate-resistant Lactococcus lactis strain C41-2, derived from wild-type L.
      lactis MG1363 through selection for growth on cholate-containing medium,
      displayed a reduced accumulation of cholate due to an enhanced active efflux.
      However, L. lactis C41-2 was not cross resistant to deoxycholate or cationic
      drugs, such as ethidium and rhodamine 6G, which are typical substrates of the
      multidrug transporters LmrP and LmrA in L. lactis MG1363. The cholate efflux
      activity in L. lactis C41-2 was not affected by the presence of valinomycin plus
      nigericin, which dissipated the proton motive force. In contrast, cholate efflux
      in L. lactis C41-2 was inhibited by ortho-vanadate, an inhibitor of P-type
      ATPases and ATP-binding cassette transporters. Besides ATP-dependent drug
      extrusion by LmrA, two other ATP-dependent efflux activities have previously been
      detected in L. lactis, one for the artificial pH probe 2',7'-bis-(2-carboxyethyl)
      5(and 6)-carboxyfluorescein (BCECF) and the other for the artificial pH probe N
      (fluorescein thio-ureanyl)-glutamate (FTUG). Surprisingly, the efflux rate of
      BCECF, but not that of FTUG, was significantly enhanced in L. lactis C41-2.
      Further experiments with L. lactis C41-2 cells and inside out membrane vesicles
      revealed that cholate and BCECF inhibit the transport of each other. These data
      demonstrate the role of an ATP-dependent multispecific organic anion transporter
      in cholate resistance in L. lactis.

PMID- 10960107
TI  - The NosX and NirX proteins of Paracoccus denitrificans are functional homologues:
      their role in maturation of nitrous oxide reductase.
AB  - The nos (nitrous oxide reductase) operon of Paracoccus denitrificans contains a
      nosX gene homologous to those found in the nos operons of other denitrifiers.
      NosX is also homologous to NirX, which is so far unique to P. denitrificans.
      Single mutations of these genes did not result in any apparent phenotype, but a
      double nosX nirX mutant was unable to reduce nitrous oxide. Promoter-lacZ assays
      and immunoblotting against nitrous oxide reductase showed that the defect was not
      due to failure of expression of nosZ, the structural gene for nitrous oxide
      reductase. Electron paramagnetic resonance spectroscopy showed that nitrous oxide
      reductase in cells of the double mutant lacked the Cu(A) center. A twin-arginine
      motif in both NosX and NirX suggests that the NosX proteins are exported to the
      periplasm via the TAT translocon.

PMID- 10960106
TI  - Mutations in multidrug efflux homologs, sugar isomerases, and antimicrobial
      biosynthesis genes differentially elevate activity of the sigma(X) and sigma(W)
      factors in Bacillus subtilis.
AB  - The sigma(X) and sigma(W) extracytoplasmic function sigma factors regulate more
      than 40 genes in Bacillus subtilis. sigma(W) activates genes which function in
      detoxification and the production of antimicrobial compounds, while sigma(X)
      activates functions that modify the cell envelope. Transposon mutagenesis was
      used to identify loci which negatively regulate sigma(W) or sigma(X) as judged by
      up-regulation from the autoregulatory promoter site P(W) or P(X). Fourteen
      insertions that activate P(W) were identified. The largest class of insertions
      are likely to affect transport. These include insertions in genes encoding two
      multidrug efflux protein homologs (yqgE and yulE), a component of the
      oligopeptide uptake system (oppA), and two transmembrane proteins with weak
      similarity to transporters (yhdP and yueF). Expression from P(W) is also elevated
      as a result of inactivation of at least one member of the sigma(W) regulon
      (ysdB), an ArsR homolog (yvbA), a predicted rhamnose isomerase (yulE), and a gene
      (pksR) implicated in synthesis of difficidin, a polyketide antibiotic. In a
      parallel screen, we identified seven insertions that up-regulate P(X).
      Remarkably, these insertions were in functionally similar genes, including a
      multidrug efflux homolog (yitG), a mannose-6-phosphate isomerase gene (yjdE), and
      loci involved in antibiotic synthesis (srfAB and possibly yogA and yngK).
      Significantly, most insertions that activate P(W) have little or no effect on
      P(X), and conversely, insertions that activate P(X) have no effect on P(W). This
      suggests that these two regulons respond to distinct sets of molecular signals
      which may include toxic molecules which are exported, cell density signals, and
      antimicrobial compounds.

PMID- 10960108
TI  - The flagellar filament of Rhodobacter sphaeroides: pH-induced polymorphic
      transitions and analysis of the fliC gene.
AB  - Flagellar motility in Rhodobacter sphaeroides is notably different from that in
      other bacteria. R. sphaeroides moves in a series of runs and stops produced by
      the intermittent rotation of the flagellar motor. R. sphaeroides has a single,
      plain filament whose conformation changes according to flagellar motor activity.
      Conformations adopted during swimming include coiled, helical, and apparently
      straight forms. This range of morphological transitions is larger than that in
      other bacteria, where filaments alternate between left- and right-handed helical
      forms. The polymorphic ability of isolated R. sphaeroides filaments was tested in
      vitro by varying pH and ionic strength. The isolated filaments could form open
      coiled, straight, normal, or curly conformations. The range of transitions made
      by the R. sphaeroides filament differs from that reported for Salmonella enterica
      serovar Typhimurium. The sequence of the R. sphaeroides fliC gene, which encodes
      the flagellin protein, was determined. The gene appears to be controlled by a
      sigma(28)-dependent promoter. It encodes a predicted peptide of 493 amino acids.
      Serovar Typhimurium mutants with altered polymorphic ability usually have amino
      acid changes at the terminal portions of flagellin or a deletion in the central
      region. There are no obvious major differences in the central regions to explain
      the difference in polymorphic ability. In serovar Typhimurium filaments, the
      termini of flagellin monomers have a coiled-coil conformation. The termini of R.
      sphaeroides flagellin are predicted to have a lower probability of coiled coils
      than are those of serovar Typhimurium flagellin. This may be one reason for the
      differences in polymorphic ability between the two filaments.

PMID- 10960109
TI  - Characterization of Escherichia coli DNA lesions generated within J774
      macrophages.
AB  - Macrophages are armed with multiple oxygen-dependent and -independent
      bactericidal properties. However, the respiratory burst, generating reactive
      oxygen species, is believed to be a major cause of bacterial killing. We
      exploited the susceptibility of Escherichia coli in macrophages to characterize
      the effects of the respiratory burst on intracellular bacteria. We show that E.
      coli strains recovered from J774 macrophages exhibit high rates of mutations. We
      report that the DNA damage generated inside macrophages includes DNA strand
      breaks and the modification 8-oxo-2'-deoxyguanosine, which are typical oxidative
      lesions. Interestingly, we found that under these conditions, early in the
      infection the majority of E. coli cells are viable but gene expression is
      inhibited. Our findings demonstrate that macrophages can cause severe DNA damage
      to intracellular bacteria. Our results also suggest that protection against the
      macrophage-induced DNA damage is an important component of the bacterial defense
      mechanism within macrophages.

PMID- 10960110
TI  - Function of the sigma(E) regulon in dead-cell lysis in stationary-phase
      Escherichia coli.
AB  - Elevation of active sigma(E) levels in Escherichia coli by either repressing the
      expression of rseA encoding an anti-sigma(E) factor or cloning rpoE in a
      multicopy plasmid, led to a large decrease in the number of dead cells and the
      accumulation of cellular proteins in the medium in the stationary phase. The
      numbers of CFU, however, were nearly the same as those of the wild type or cells
      devoid of the cloned gene. In the wild-type cells, rpoE expression was increased
      in the stationary phase and a low-level release of intracellular proteins was
      observed. These results suggest that dead cell lysis in stationary-phase E. coli
      occurs in a sigma(E)-dependent fashion. We propose there is a novel physiological
      function of the sigma(E) regulon that may guarantee cell survival in prolonged
      stationary phase by providing nutrients from dead cells for the next generation.

PMID- 10960112
TI  - The amino terminus of Pseudomonas aeruginosa outer membrane protein OprF forms
      channels in lipid bilayer membranes: correlation with a three-dimensional model.
AB  - Pseudomonas aeruginosa OprF forms 0.36-nS channels and, rarely, 2- to 5-nS
      channels in lipid bilayer membranes. We show that a protein comprising only the N
      terminal 162-amino-acid domain of OprF formed the smaller, but not the larger,
      channels in lipid bilayers. Circular dichroism spectroscopy indicated that this
      protein folds into a beta-sheet-rich structure, and three-dimensional comparative
      modeling revealed that it shares significant structural similarity with the amino
      terminus of the orthologous protein Escherichia coli OmpA, which has been shown
      to form a beta-barrel. OprF and OmpA share only 15% identity in this domain, yet
      these results support the utility of modeling such widely divergent beta-barrel
      domains in three dimensions in order to reveal similarities not readily apparent
      through primary sequence comparisons. The model is used to further hypothesize
      why porin activity differs for the N-terminal domains of OprF and OmpA.

PMID- 10960111
TI  - Predicted highly expressed genes of diverse prokaryotic genomes.
AB  - Our approach in predicting gene expression levels relates to codon usage
      differences among gene classes. In prokaryotic genomes, genes that deviate
      strongly in codon usage from the average gene but are sufficiently similar in
      codon usage to ribosomal protein genes, to translation and transcription
      processing factors, and to chaperone-degradation proteins are predicted highly
      expressed (PHX). By these criteria, PHX genes in most prokaryotic genomes include
      those encoding ribosomal proteins, translation and transcription processing
      factors, and chaperone proteins and genes of principal energy metabolism. In
      particular, for the fast-growing species Escherichia coli, Vibrio cholerae,
      Bacillus subtilis, and Haemophilus influenzae, major glycolysis and tricarboxylic
      acid cycle genes are PHX. In Synechocystis, prime genes of photosynthesis are
      PHX, and in methanogens, PHX genes include those essential for methanogenesis.
      Overall, the three protein families-ribosomal proteins, protein synthesis
      factors, and chaperone complexes-are needed at many stages of the life cycle, and
      apparently bacteria have evolved codon usage to maintain appropriate growth,
      stability, and plasticity. New interpretations of the capacity of Deinococcus
      radiodurans for resistance to high doses of ionizing radiation is based on an
      excess of PHX chaperone-degradation genes and detoxification genes. Expression
      levels of selected classes of genes, including those for flagella, electron
      transport, detoxification, histidine kinases, and others, are analyzed. Flagellar
      PHX genes are conspicuous among spirochete genomes. PHX genes are positively
      correlated with strong Shine-Dalgarno signal sequences. Specific regulatory
      proteins, e.g., two-component sensor proteins, are rarely PHX. Genes involved in
      pathways for the synthesis of vitamins record low predicted expression levels.
      Several distinctive PHX genes of the available complete prokaryotic genomes are
      highlighted. Relationships of PHX genes with stoichiometry, multifunctionality,
      and operon structures are discussed. Our methodology may be used complementary to
      experimental expression analysis.

PMID- 10960113
TI  - The Escherichia coli O111 and Salmonella enterica O35 gene clusters: gene
      clusters encoding the same colitose-containing O antigen are highly conserved.
AB  - O antigen is part of the lipopolysaccharide present in the outer membrane of gram
      negative bacteria. Escherichia coli and Salmonella enterica each have many forms
      of O antigen, but only three are common to the two species. It has been found
      that, in general, O-antigen genes are of low GC content. This deviation in GC
      content from that of typical S. enterica or E. coli genes (51%) is thought to
      indicate that the O-antigen DNA originated in species other than S. enterica or
      E. coli and was captured by lateral transfer. The O-antigen structure of
      Salmonella enterica O35 is identical to that of E. coli O111, commonly found in
      enteropathogenic E. coli strains. This O antigen, which has been shown to be a
      virulence factor in E. coli, contains colitose, a 3,6-dideoxyhexose found only
      rarely in the Enterobacteriaceae. Sequencing of the O35-antigen gene cluster of
      S. enterica serovar Adelaide revealed the same gene order and flanking genes as
      in E. coli O111. The divergence between corresponding genes of these two gene
      clusters at the nucleotide level ranges from 21.8 to 11.7%, within the normal
      range of divergence between S. enterica and E. coli. We conclude that the
      ancestor of E. coli and S. enterica had an O antigen identical to the O111 and
      O35 antigens, respectively, of these species and that the gene cluster encoding
      it has survived in both species.

PMID- 10960116
TI  - Bacillus subtilis YvrK is an acid-induced oxalate decarboxylase.
AB  - Bacillus subtilis has been shown to express a cytosolic oxalate decarboxylase (EC
      4.1.1.2). The enzyme was induced in acidic growth media, particularly at pH 5.0,
      but not by oxalate. The enzyme was purified, and N-terminal sequencing identified
      the protein to be encoded by yvrK. The role of the first oxalate decarboxylase to
      be identified in a prokaryote is discussed.

PMID- 10960114
TI  - Lantibiotic biosynthesis: interactions between prelacticin 481 and its putative
      modification enzyme, LctM.
AB  - Class AII and AIII lantibiotics and mersacidin are antibacterial peptides
      containing unusual residues obtained by posttranslational modifications of
      prepeptides, presumably catalyzed by LanM. LctM, the LanM for lacticin 481, is
      essential for the production of this class AII lantibiotic. Using the yeast two
      hybrid system, we showed direct contact between the prelacticin 481 and LctM,
      supporting the proposed LctM function. Sixteen domains are conserved between the
      10 known LanM proteins, whereas three additional domains were found only in class
      AII LanM proteins and in MrsM, the LanM for mersacidin. All the truncated LctM
      proteins that we tested presented impaired LctA-binding activity.

PMID- 10960115
TI  - Evidence for multimerization of neu proteins involved in polysialic acid
      synthesis in Escherichia coli K1 using improved LexA-based vectors.
AB  - Recently, M. Dmitrova et al. (Mol. Gen. Genet. 257:205-212, 1998) described a
      LexA-based genetic system to monitor protein-protein interactions in an
      Escherichia coli background. However, the plasmids used in this system, pMS604
      and pDP804, were not readily amenable for general use. In this report, we
      describe modifications of both plasmids that allow fragments of DNA to be fused
      to either vector in any reading frame. Homodimerization and heterodimerization of
      full-length proteins involved in polysialic acid synthesis in E. coli K1, as well
      as heterodimerization between a full-length protein and a protein fragment,
      demonstrate the usefulness of the modified plasmids for investigating bacterial
      protein-protein interactions in vivo.

PMID- 10960117
TI  - Mutational analysis of genes encoding the early flagellar components of
      Helicobacter pylori: evidence for transcriptional regulation of flagellin A
      biosynthesis.
AB  - We investigated the roles of fliF, fliS, flhB, fliQ, fliG, and fliI of
      Helicobacter pylori, predicted by homology to encode structural components of the
      flagellar basal body and export apparatus. Mutation of these genes resulted in
      nonmotile, nonflagellate strains. Western blot analysis showed that all the
      mutants had considerably reduced levels of both flagellin subunits and of FlgE,
      the flagellar hook protein. RNA slot blot hybridization showed reduced levels of
      flaA mRNA, indicating that transcription of the major flagellin gene is inhibited
      in the absence of the early components of the flagellar-assembly pathway. This is
      the first demonstration of a checkpoint in H. pylori flagellar assembly.

PMID- 10960119
TI  - Discrimination between Atlantic and Pacific Subspecies of Northern Bluefin Tuna
      (Thunnus thynnus) by Magnetic-Capture Hybridization Using Bacterial Magnetic
      Particles.
AB  - The previously developed magnetic-capture hybridization technique employing
      bacterial magnetic particles was applied to discriminate between Atlantic and
      Pacific subspecies of the northern bluefin tuna (Thunnus thynnus) using specific
      DNA sequences. Nucleotide sequences of a 925-bp fragment (ATCO) flanking the
      mitochondrial ATPase and cytochrome oxidase subunit III genes in these two
      subspecies were compared. Two regions having single-nucleotide and three
      nucleotide differences between the subspecies were adopted to design DNA probes
      (NR1, 21-mer; NR2, 29-mer), and two internal primer sets were designed to amplify
      DNA fragments containing these regions. The DNA probes were immobilized on
      bacterial magnetic particles via streptavidin-biotin conjugation and subjected to
      magnetic-capture hybridization with the digoxigenin-labeled fragments amplified
      using the internal primers. The luminescence intensities of DNA on bacterial
      magnetic particles obtained by hybridization between the probes and the
      complementary fragments were higher than those obtained by hybridization with
      noncomplementary fragments. These data suggest that this system employing DNA on
      bacterial magnetic particles may be useful for discrimination of these two
      subspecies by recognizing a single-nucleotide difference.

PMID- 10960118
TI  - Genetic analysis of an incomplete mutS gene from Pseudomonas putida.
AB  - We genetically characterized the Pseudomonas putida mutS gene and found that it
      encodes a smaller MutS protein than do the genes of other bacteria. This gene is
      able to function in the mutS mutants of Escherichia coli and Bacillus subtilis. A
      P. putida mutS mutant has a mutation frequency 1,000-fold greater than that of
      the wild-type strain.

PMID- 10960120
TI  - Improved Plate Assay for Antifouling Substances Using Blue Mussel Mytilus edulis
      galloprovincialis.
AB  - An improved plate assay for screening antifoulants against blue mussels, Mytilus
      edulis galloprovincialis, was designed based on an assay contrived by Ina and
      colleagues. To obtain more reliable results, the number of test mussels for one
      sample was increased from 4 to 10. Cardboard pieces used as test plates were cut
      into rectangular shapes to separate the test sample and the blank zone, which are
      of the same area. Activity was expressed numerically. In this improved method,
      several inhibitors of byssus thread formation were isolated by using a smaller
      amount of sample per area than in the original method. Previously our laboratory
      developed a foot-stimulating bioassay for the same purpose. This method requires
      only a small amount of sample and is therefore useful for isolating antifouling
      substances from natural sources, including marine organisms. However, the
      inhibition of byssus thread formation cannot be directly evaluated in the foot
      stimulating method. The improved plate assay and the foot-stimulating method were
      examined and compared using a secosterol from the sponge Dysidea granulosa and
      CuSO(4).

PMID- 10960121
TI  - Use of Polymerase Chain Reaction for the Detection of Infectious Hypodermal and
      Hematopoietic Necrosis Virus in Penaeid Shrimp.
AB  - A rapid and reliable polymerase chain reaction (PCR) method was developed for the
      detection of infectious hypodermal and hematopoietic necrosis virus (IHHNV) in
      penaeid shrimp. The oligonucleotide primers amplify a 1681-bp fragment of IHHNV,
      which encompasses the coding sequence for one of the viral coat proteins. The PCR
      method detects IHHNV in hemolymph and homogenized tissue obtained from the
      cephalothorax or pleopods of infected shrimp. The technique was also successfully
      applied to tissue samples preserved in 70% ethanol. The correct size fragment was
      amplified using IHHNV obtained from six different geographic regions in three
      different species of penaeid shrimp. No DNA extraction method was necessary for
      this technique. The use of hemolymph or pleopods provides a nondestructive
      screening method by which to test juveniles and adult broodstock for the presence
      of IHHNV.

PMID- 10960122
TI  - Tissue-Specific Induction of Hsp90 mRNA and Plasma Cortisol Response in Chinook
      Salmon following Heat Shock, Seawater Challenge, and Handling Challenge.
AB  - In studying the whole-body response of chinook salmon (Oncorhynchus tshawytscha)
      to various stressors, we found that 5-hour exposure to elevated temperature (mean
      21.6 degrees C; + 10.6 degrees C over ambient) induced a marked increase in Hsp90
      messenger RNA accumulation in heart, brain, gill, muscle, liver, kidney, and tail
      fin tissues. The most vital tissues (heart, brain, gill, and muscle) showed the
      greatest Hsp90-mRNA response, with heart tissue increasing approximately 35-fold.
      Heat shock induced no increase in plasma cortisol. In contrast, a standard
      handling challenge induced high plasma cortisol levels, but no elevation in Hsp90
      mRNA in any tissue, clearly separating the physiological and cellular stress
      responses. We saw no increase either in tissue Hsp90 mRNA levels or in plasma
      cortisol concentrations after exposing the fish to seawater overnight.

PMID- 10960123
TI  - Microsatellite Polymorphism and the Population Structure of the Black Tiger
      Shrimp (Penaeus monodon) in Thailand.
AB  - Genetic variation and differentiation of Thai Penaeus monodon from five
      geographic locations (Chumphon, Trad, Phangnga, Satun, and Trang) were
      investigated using five microsatellite loci (CUPmo18, Di25, Di27, CSCUPmo1, and
      CSCUPmo2). The number of alleles across the five loci ranged from 19 to 30, and
      heterozygosities ranged from 0.49 to 0.95. The mean number of alleles and
      effective number of alleles per locus were 21.0 to 26.6 and 13.1 to 20.4,
      respectively. The average heterozygosity across all investigated samples was
      0.78, indicating high genetic diversity in this species. Geographic heterogeneity
      analysis of the results from two of the loci, CUPmo18 and Di25, showed
      significant differences among the Gulf of Thailand (Trad and Chumphon) but not
      the Andaman samples. Comparison between regions revealed significant
      heterogeneity of the Andaman and Trad P. monodon (P <.001), whereas those from
      Chumphon and the Andaman were genetically similar (P >.05). Significant genetic
      differentiation was consistently observed between the Andaman-Trad samples (F(ST)
      = 0.0101, P <.0001) and the Chumphon-Trad samples (F(ST) = 0.0101, P <.0001). On
      the basis of our analyses, the investigated samples from five geographic
      locations were allocated to three distinct populations composed of the Andaman
      Sea (A), Chumphon (B), and Trad (C).

PMID- 10960124
TI  - Conservative Structure of the Plaque Matrix Protein of Mussels in the Genus
      Mytilus.
AB  - The complementary DNA encoding the byssal plaque matrix protein (fp-2) of the
      mussel Mytilus coruscus was isolated. The predicted amino acid sequence (474
      amino acids) consists of four parts: the signal peptide, the amino-terminal
      nonrepetitive domain, the central repetitive domain containing 11 repeats of an
      epidermal growth factor-like motif, and the carboxy-terminal nonrepetitive
      domain. The amino acid sequence is 82.7%, similar to that of fp-2 of Mytilus
      galloprovincialis, and the basic structure including number and motif of repeats
      is highly conservative. Amino acid substitutions are less frequent in "consensus
      positions" of the central repetitive domain (13.1%), and most of them are changes
      from irregular amino acids to regular ones. Thus, the structure of fp-2 was found
      to be conservative between species. It was presumed that the basic structure of
      fp-2 is unchangeable to maintain the flexible and durable matrix structure and
      that variation is not required because fp-2 is protected by other surface
      proteins.

PMID- 10960125
TI  - Marine Surfaces and the Expression of Specific Byssal Adhesive Protein Variants
      in Mytilus.
AB  - Mytilus foot protein-3 (Mfp-3) is a highly polymorphic protein family located in
      the byssal adhesive plaques of blue mussels. Previous evidence suggested that the
      deposition of selected Mfp-3 variants might be influenced by the type of surface
      to which the mussel attaches; therefore, we undertook to rigorously investigate
      whether a correlation exists between surface type and Mfp-3 variants. Two
      hypotheses were tested in M. galloprovincialis and M. edulis. One hypothesis was
      that individual mussels deposit specific Mfp-3 variants on different surfaces.
      Laser desorption-ionization mass spectrometry was used to detect Mfp-3 variants
      on the underside of byssal adhesive plaques. The other hypothesis was that the
      transcription of specific Mfp-3s is induced by different surfaces. This was
      measured by using denaturing gradient gel electrophoresis to separate closely
      related amplified complementary DNAs among individual mussels attached to
      stainless steel, glass, or polyethylene surfaces. Band stabs of several Mfp-3
      cDNAs were sequenced. The results clearly showed that individual mussels secreted
      a similar suite of Mfp-3 variants onto glass, plastic, and steel. Likewise, the
      expression of Mfp-3 cDNA transcripts in individual mussels revealed no clear
      correlation between messenger RNA expression and the type of surface. Thus, the
      expression and secretion of specific Mfp-3 variants do not appear to be surface
      induced. These results underscore the importance of following individual mussels
      rather than populations in surface studies.

PMID- 10960126
TI  - Infectious Pancreatic Necrosis Virus RNA Cleavage In Vitro by Hammerhead
      Ribozymes and Enhancement of Ribozyme Catalysis by Oligonucleotide Facilitators.
AB  - Infectious pancreatic necrosis virus (IPNV), an aquatic birnavirus, has a
      bisegmented double-stranded RNA genome consisting of a 3.2-kb A segment and a 2.9
      kb B segment. To determine the function of IPNV's viral proteins and to study the
      effects of viral RNA cleavage by hammerhead ribozymes, we cloned and sequenced
      the IPNV E1S strain of the A segment. After sequencing, we continued to study the
      virus pathogens inhibited by ribozyme cleavage and analyzed the cleavage of the
      virus RNA in vitro. The templates (VP2, 1220 bp) for in vitro transcription of
      S569 and S969 (substrates 569 and 969 bp in length) were synthesized by
      polymerase chain reaction. The DNA templates of hammerhead ribozymes targeted
      different sites in the partial sense RNA of IPNV. These templates were chemically
      synthesized RNAs prepared by runoff transcription of amplification products or
      synthetic DNA templates containing a T7 RNA polymerase promoter, and were used to
      characterize several properties of the cleavage reaction at 25 degrees C in 12 mM
      Mg(2+). Under this condition (25 degrees C, 12 mM Mg(2+)), the hammerhead
      ribozymes formed an estimated fraction of product during the reaction of only 30%
      in cleaving long RNA substrates in vitro. Short DNA facilitators (12 or 24-mers)
      that bind adjacent to either the 3' or 5' end of the ribozyme enhanced the rate
      of cleavage of the long RNA substrates containing 569 and 969 nucleotides,
      respectively, in trans. The hammerhead ribozymes with 3'-end facilitators reacted
      more efficiently (i.e., 65%).

PMID- 10960127
TI  - Overexpression of a Zebrafish ARNT2-like Factor Represses CYP1A Transcription in
      ZLE Cells.
AB  - Aryl hydrocarbon receptor nuclear translocator (ARNT) factors belong to a novel
      basic-helix-loop-helix-PAS (bHLH-PAS) transcription factor family that controls a
      variety of physiological and developmental processes. In a previous study, we
      obtained a partial complementary DNA fragment of an ARNT2-like factor from
      zebrafish embryo, liver, and other tissues by reverse transcription-polymerase
      chain reaction. In an effort to characterize the function of this factor, we
      screened an embryonic complementary DNA library and obtained a complete cDNA of
      this ARNT2-like factor, zARNT2A. The deduced protein sequence of zARNT2A
      encompasses the basic-helix-loop-helix and PAS-A/B motifs and shares highest
      sequence similarity with the amino-terminal half of mouse ARNT2 factor. However,
      it lacks a carboxy-terminal transactivation motif following the PAS-A/B motifs.
      Transient expression of zARNT2A in cultured cells resulted in repression of TCDD
      dependent CYP1A transcription. Whole-mount in situ hybridization revealed that
      zARNT2A is expressed in brain and pronephros at prime-5 stages. In adult fish,
      zARNT2A messenger RNA is transcribed in a wide range of tissues, which indicates
      that zARNT2A and its corresponding signal transduction mechanisms have important
      roles in fish development and other physiological aspects.

PMID- 10960128
TI  - In Vitro Synthesis of Proteoglycans and Collagen in Primary Cultures of Mantle
      Cells from the Nacreous Mollusk, Haliotis tuberculata: A New Model for Study of
      Molluscan Extracellular Matrix.
AB  - In Mollusca, the mantle produces an organic matrix that mineralizes in time to
      make shell. Primary mantle cell cultures from the nacreous gastropod Haliotis
      tuberculata have been established as useful experimental model to investigate in
      vitro synthesis of both proteoglycans/glycosaminoglycans (PGs/GAGs) and collagen.
      First, we tested different enzymatic digestion procedures to find the method that
      gives the highest percentage of viable and adherent cultured cells. Enzymatic
      digestion with 0.1% pronase plus 0.1% collagenase was routinely used. Six days
      after the initiation of culture, about 80% of cells were viable, among which 20%
      were adherent as quantified by the MTT reduction assay. In addition, the protein
      synthesis estimated by [(3)H]leucine incorporation remained constant during this
      period. For the first time, we demonstrated a de novo synthesis of PGs/GAGs and
      collagen in primary cultures of mantle cells. After 48 hours of labeling, among
      the [(3)H]-d-glucosamine macromolecules synthesized, [(3)H]PGs/GAGs represented
      43%, divided into 45% heparan sulfate, 37% chondroitin/dermatan sulfate, and 6%
      hyaluronic acid. Early elution on anion-exchange chromatography of these PGs/GAGs
      indicated that most of them appeared as undersulfated GAG molecules. De novo
      synthesis of collagen represents 4.52% +/- 0.84% (SD) with respect to the total
      protein synthesis. Such a model will facilitate studies on the synthesis of
      PGs/GAGs and collagen as components of the extracellular matrix and its
      regulation in Mollusca. Both PGs/GAGs and collagen participate in molecular
      events that regulate cell adhesion, migration, and proliferation. Further studies
      with this type of in vitro model should provide knowledge about novel aspects of
      molluscan cell signaling, in relation to extracellular matrix components.

PMID- 10960129
TI  - Two Tandemly Arrayed Transfer-RNA-Derived SINEs of the Medaka (Oryzias latipes).
AB  - Two tandemly arrayed short interspersed repetitive element (SINE) sequences were
      found in medaka (Oryzias latipes). These two SINE sequences, designated SINE1 and
      SINE2, were flanked by a 180-bp AT-rich region. Both appeared to be derived from
      transfer RNA. The former exhibited 80% sequence homology to human tRNA(Ala) and
      the latter exhibited 94% sequence homology to rat tRNA(Ser). SINE1 contained the
      retroviral U5 region, whereas SINE2 did not. This is the first sequence-level
      demonstration of the existence of neighboring SINEs in medaka.

PMID- 10960130
TI  - Quantitative structure-activity relationships (QSAR) of two series of O-aryl or N
      aryl O-ethyl phosphoramidate and phosphorodiamidate fungicides incorporating
      amino acid ethyl esters.

PMID- 10960131
TI  - Potential antifungal activity and structure-activity relationships of some 2
      amino acid substituted benzo-1,3,2-dioxaphospholene, oxazaphospholine and
      diazaphospholine 2-ones.

PMID- 10960132
TI  - Dose-tissue relationships for dieldrin in nestling black-billed magpies.

PMID- 10960133
TI  - Structure-phytotoxicity relationship: comparative inhibition of selected nitrogen
      containing aromatics to root elongation of Cucumis sativus.

PMID- 10960134
TI  - Survey of selected activities relevant to exposures to soils.

PMID- 10960136
TI  - Sorption of cadmium and their effects on growth, protein contents, and
      photosynthetic pigment composition of Veronica anagallis-aquatica L. and
      Ranunculus aquatilis L.

PMID- 10960135
TI  - Detection of biological efficiency of Fe(III) complexes with heterocyclic N-donor
      ligand nicotinamide (nia) using algal assay.

PMID- 10960137
TI  - Lethal concentration of Cu in the neotropical fish Cnesterodon decemmaculatus
      (Pisces, cyprinodontiformes).

PMID- 10960138
TI  - Copper contamination and cadmium, silver, and zinc concentrations in the
      digestive glands of American lobster (Homarus americanus) from the Inner Bay of
      Fundy, Atlantic Canada.

PMID- 10960139
TI  - Assessment of the trace metal levels in two species of mussels from the Agadir
      Marine Bay, South of Morocco.

PMID- 10960140
TI  - Kinetics of Vanadium Bioaccumulation by the brackish water hydroid Cordylophora
      caspia (Pallas).

PMID- 10960141
TI  - Evaluation of environmental estrogens with a fish cell line.

PMID- 10960142
TI  - Cypermethrin-induced apoptosis in the telencephalon of Physalaemus biligonigerus
      tadpoles (Anura: Leptodactylidae).

PMID- 10960143
TI  - Relationship between summarizing chemical parameters like AOX, TOC, TN(b), and
      toxicity tests for effluents from the chemical production.

PMID- 10960145
TI  - Assessing insecticide drift during and after center-pivot chemigation to corn
      using glass plates and gauze pads.

PMID- 10960144
TI  - Physiological responses to oxidative and heavy metal stress in seedlings of rice
      paddy, Oryza sativa L.

PMID- 10960146
TI  - Mobility and persistence of metolachlor in two common Malaysian agricultural
      soils.

PMID- 10960147
TI  - Polycyclic aromatic hydrocarbon distributions in sediments from the Mar Piccolo,
      Ionian Sea, Italy.

PMID- 10960148
TI  - Nickel speciation in soil and the relationship with its concentration in fruits.

PMID- 10960149
TI  - The inner nuclear membrane.

PMID- 10960150
TI  - Extra- and intracellular proton-binding sites of volume-regulated anion channels.
AB  - We have investigated the effects of extracellular and intracellular pH on single
      channel and macroscopic (macropatches) currents through volume-regulated anion
      channels (VRAC) in endothelial cells. Protonation of extracellular binding sites
      with an apparent pK of 4.6 increased voltage independent of the single-channel
      amplitude. Cytosolic acidification had a dual effect on VRAC currents: on the one
      hand, it increased single channel conductance by approximately 20% due to
      protonation of a group with an apparent pK of 6.5 and a Hill coefficient of 2. On
      the other hand, it reduced channel activity due to protonation of a group with an
      apparent pK of 6.3 and a Hill coefficient of 2.1. This dual effect enhances the
      macroscopic current at a slightly acidic pH but inhibits it at more acidic pH.
      Cytosolic alkalization also reduced channel activity with a pK of 8.4 and a Hill
      coefficient of 1.9, but apparently did not affect single-channel conductance.
      These data show that VRAC channels are maintained in an active state in a narrow
      pH range around the normal physiological pH and shut down outside this range.
      They also show that HEPES-buffered pipette solutions do not effectively buffer pH
      in the vicinity of the VRAC channels.

PMID- 10960151
TI  - Temperature dependence of pyrethroid modification of single sodium channels in
      rat hippocampal neurons.
AB  - Pyrethroid modulation of sodium channels is unique in the sense that it is highly
      dependent on temperature, the potency being augmented by lowering the
      temperature. To elucidate the mechanisms underlying the negative temperature
      dependence of pyrethroid action, single sodium channel currents were recorded
      from cultured rat hippocampal neurons using the inside-out configuration of patch
      clamp technique, and the effects of the pyrethroid tetramethrin were compared at
      22 and 12 degrees C. Tetramethrin-modified sodium channels opened with short
      closures and/or transitions to subconductance levels at 22 and 12 degrees C. The
      time constants of the burst length histograms for tetramethrin-modified channels
      upon depolarization to -60 mV were 7. 69 and 14.46 msec at 22 and 12 degrees C,
      respectively (Q(10) = 0. 53). Tetramethrin at 10 microm modified 17 and 23% of
      channels at 22 and 12 degrees C, respectively, indicating that the sensitivity of
      the sodium channel of rat hippocampal neurons to tetramethrin was almost the same
      as that of tetrodotoxin-sensitive sodium channels of rat dorsal root ganglion
      neurons and rat cerebellar Purkinje neurons. The time constants for burst length
      in tetramethrin-modified sodium channels upon repolarization to -100 mV from -30
      mV were 8.26 and 68. 80 msec at 22 and 12 degrees C (Q(10) = 0.12), respectively.
      The prolongation of tetramethrin-modified whole-cell sodium tail currents upon
      repolarization at lower temperature was ascribed to a prolongation of opening of
      each channel. Simple state models were introduced to interpret behaviors of
      tetramethrin-modified sodium channels. The Q(10) values for transition rate
      constants upon repolarization were extremely large, indicating that temperature
      had a profound effect on tetramethrin-modified sodium channels.

PMID- 10960153
TI  - The swelling-activated anion conductance in the mouse renal inner medullary
      collecting duct cell line mIMCD-K2.
AB  - Swelling-activated Cl(-) currents (I(Cl,swell)) have been characterized in a
      mouse renal inner medullary collecting duct cell line (mIMCD-K2). Currents
      activated by exposing the cells to hypotonicity exhibited characteristic outward
      rectification and time- and voltage-dependent inactivation at positive potentials
      and showed an anion selectivity of I(-) > Br(-) > Cl(-) > Asp(-). NPPB (100
      microm) inhibited the current in a voltage independent manner, as did exposure to
      10 microm tamoxifen and 500 microm niflumic acid (NFA). In contrast, DIDS (100
      microm) blocked the current with a characteristic voltage dependency. These
      characteristics of I(Cl, swell) in mIMCD-K2 cells are essentially identical to
      those of heterologously expressed cardiac CLC-3. A defining feature of CLC-3 is
      that activation of PKC by PDBu inhibits the conductance. In mIMCD-K2 cells
      preincubation with PDBu (100 nm) prevented the activation of I(Cl,swell) by
      hypotonicity. However, PDBu inhibition of I(Cl,swell) was reversed after PDBu
      withdrawal, but this was refractory to subsequent PDBu inhibition. Activation of
      either the cystic fibrosis transmembrane conductance regulator (CFTR) or Ca(2+)
      activated Cl(-) conductance (CaCC), which are coexpressed in mIMCD-K2 cells prior
      to PDBu treatment, abolished the PDBu inhibition of I(Cl,swell). Control of
      I(Cl,swell) by PKC therefore depends on the physiological status of the cell. In
      intact mIMCD-K2 layers in Ussing chambers, forskolin stimulation of an inward
      short-circuit current (due to transepithelial Cl(-) secretion via apical CFTR)
      was inhibited by cell swelling upon hypotonic exposure at the basolateral
      surface. Activation of I(Cl,swell) is therefore capable of regulating
      transepithelial Cl(-) secretion and suggests that I(Cl,swell) is located at the
      basolateral membrane. PDBu exposure prior to or during hypotonic challenge was
      ineffective in reversing the swelling-activated inhibition of Cl(-) secretion,
      but tamoxifen (100 microm) abolished the hypotonic inhibition of forskolin
      stimulated short-circuit current (I(sc)). RT-PCR analysis confirmed expression of
      mRNA for members of the CLC family, including both CLC-2 and 3, in the mIMCD-K2
      cell line.

PMID- 10960152
TI  - Adaptation by corneal epithelial cells to chronic hypertonic stress depends on
      upregulation of Na:K:2Cl cotransporter gene and protein expression and ion
      transport activity.
AB  - We examined the ability of SV40-immortalized human and rabbit corneal epithelial
      cells (HCEC and RCEC, respectively) to adapt to chronic hypertonic stress. Under
      isotonic conditions, in the presence of 50 microm bumetanide, proliferation
      measured as (3)H-thymidine incorporation declined in RCEC and HCEC by 8 and 35%,
      respectively. After 48 hr exposure to 375 mOsm medium, RCEC proliferation fell by
      19% whereas in HCEC it declined by 45%. Light scattering behavior demonstrated
      that both cell lines mediate nearly complete regulatory volume increase (RVI)
      responses to an acute hypertonic (375 mOsm) challenge, which in part depend on
      bumetanide-sensitive Na-K-2Cl cotransporter (NKCC) activity. Following exposing
      RCEC for 48 hr to 375 mOsm medium, their RVI response to an acute hypertonic
      challenge was inhibited by 17%. However, in HCEC this response declined by 68%.
      During exposure to 375 mOsm medium for up to 24 hr, only RCEC upregulated NKCC
      gene and protein expression as well as bumetanide-sensitive (86)Rb influx. These
      increases are consistent with the smaller declines in RVI and proliferation
      capacity occurring during this period in RCEC than in HCEC. Therefore, adaptation
      by RCEC to chronic hypertonic stress is dependent on stimulation of NKCC gene and
      protein expression and functional activity. On the other hand, under isotonic
      conditions, HCEC RVI and proliferation are more dependent on NKCC activity than
      they are in RCEC.

PMID- 10960154
TI  - Glycosylation influences gating and pH sensitivity of I(sK).
AB  - The KvLQT1 and minK subunits that coassemble to form I(sK) channels, contain
      potential N-glycosylation sites. To examine the role of glycosylation in channel
      function, a Chinese hamster ovary cell line deficient in glycosylation (Lec-1)
      and its parental cell line (Pro-5) were transiently transfected with human KvLQT1
      (hKvLQT1) cDNA, alone and in combination with the rat (rminK) or human minK
      (hminK) cDNA. Functional KvLQT1 and I(sK) currents were expressed in both cell
      lines, although amplitudes were larger in Pro-5 than Lec-1 cells transfected with
      hKvLQT1 and hKvLQT1/hminK. For I(sK), but not KvLQT1, the voltage-dependence of
      activation was shifted to more positive voltages and the activation kinetics were
      slower in the Lec-1 compared to the Pro-5 cells. The effect of extracellular
      acidification on recombinant KvLQT1 and I(sK) currents was investigated in Pro-5
      and Lec-1 cells. Changing external pH (pH(o)) from 7.4 to 6.0 significantly
      decreased the amplitude and increased the half-activation voltage (V(1/2)) of
      KvLQT1 currents in Pro-5 and Lec-1 cells. In Pro-5 cells, decreasing pH(o)
      reduced I(sK) amplitude without increasing V(1/2), whether rminK or hminK was
      coexpressed with hKvLQT. In contrast, changing pH(o) from 7.4 to 6.0 did not
      significantly change I(sK) amplitude in Lec-1 cells. Thus, oligosaccharides
      attached to the minK subunit affect not only the gating properties, but also the
      pH sensitivity of I(sK).

PMID- 10960155
TI  - Lithium and protein kinase C modulators regulate swelling-activated K-Cl
      cotransport and reveal a complete phosphatidylinositol cycle in low K sheep
      erythrocytes.
AB  - K-Cl cotransport (COT), a ouabain-insensitive, Cl-dependent bidirectional K flux,
      is ubiquitously present in all cells, plays a major role in ion and volume
      homeostasis, and is activated by cell swelling and a variety of chemical
      interventions. Lithium modulates several cation transport pathways and inhibits
      phospholipid turnover in red blood cells (RBCs). Lithium also inhibits K-Cl COT
      by an unknown mechanism. To test the hypothesis whereby Li inhibits swelling
      activated K-Cl COT by altering either its osmotic response, its regulation, or by
      competing with K for binding sites, low K (LK) sheep (S) RBCs were loaded with Li
      by Na/Li exchange or the cation ionophore nystatin. K-Cl COT was measured as the
      Cl-dependent, ouabain-insensitive K efflux or Rb influx. The results show that Li
      altered the cell morphology, and increased both cell volume and diameter.
      Internal (Li(i)) but not external (Li(o)) Li inhibited swelling-activated K-Cl
      COT by 85% with an apparent K(i) of approximately 7 mm. In Cl, Li(i) decreased K
      efflux at relative cell volumes between 0.9 and 1.2, and at external pHs between
      7.2 and 7.4. Li(i) reduced the V(max) and increased the K(m) for K efflux in Cl.
      Furthermore, Li(i) increased the production of diacylglycerol in a bimodal
      fashion, without significant effects on the phosphatidylinositol concentration,
      and revealed the presence of a complete PI cycle in LK SRBCs. Finally, phorbol
      ester treatment and PD89059, an inhibitor of mitogen-activated protein kinase
      (ERK2) kinase, caused a time-dependent inhibition of K-Cl COT. Hence, Li(i)
      appears to inhibit K-Cl COT by acting at an allosteric site on the transporter or
      its putative regulators, and by modulation of the cellular phospholipid
      metabolism and a PKC-dependent regulatory pathway, causes an altered response of
      K-Cl COT to pH and volume.

PMID- 10960156
TI  - Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior.
AB  - BACKGROUND: Dysfunction of serotoninergic transmission could predispose to
      excessive alcohol consumption and dependence. The functional polymorphism of the
      serotonin transporter gene (5-HTTLPR) has been associated with different
      disorders, including alcoholism. Considering the likelihood of heterogeneity in
      the "alcohol dependence" phenotype, 5-HTTLPR may be more specifically implicated
      in subsamples of patients or in related traits of alcoholism, such as
      impulsivity. METHODS: We analyzed the role of this functional polymorphism in the
      risk for suicide attempt in a population of male alcohol-dependent subjects. One
      hundred ten male alcohol-dependent patients (DSM-III-R criteria), French for at
      least two generations, were personally interviewed with the Diagnostic Interview
      for Genetic Studies and compared with 61 unaffected blood donors. RESULTS: The
      "short" (S) allele of the 5-HTTLPR appeared to be unrelated to alcohol dependence
      and comorbid depression in our sample, but was found associated with an increased
      risk for suicide attempts. This association was predominantly observed in severe
      and repetitive suicide attempts, with a significant dose effect of the S allele
      (0, 1, or 2) on the number and the severity of suicide attempts. CONCLUSIONS:
      Mood disorders and alcohol dependence may interact with a genetic (relative)
      deficiency in serotonin reuptake, thereby increasing the risk for
      aggressive/impulsive behaviors such as suicide attempts.

PMID- 10960157
TI  - Factors predicting the onset of adolescent drinking in families at high risk for
      developing alcoholism.
AB  - BACKGROUND: With a longitudinal prospective design, the purpose of this study was
      1) to assess, with survival analysis, the age of onset of drinking in relation to
      family history of alcoholism; 2) to examine the importance of selected
      neurobiological and psychosocial risk factors in predicting the onset to drink;
      and 3) to determine if the age of onset of substance dependence problems differed
      by risk group status. METHODS: One hundred twenty-five children and adolescents
      were evaluated annually (N = 638 evaluations), providing up to seven annual waves
      of longitudinal data. Survival analyses were performed to determine the age of
      onset of regular drinking and the age of onset for substance abuse/dependence.
      The age of onset of regular drinking outcome was modeled using familial density
      of alcoholism and four factors, which included neurobiological indices of
      development (postural sway and P300), personality characteristics, academic
      achievement, self-esteem, and trait anxiety. RESULTS: High-risk
      children/adolescents showed a significantly earlier age of onset of drinking and
      an earlier age of onset for substance abuse problems. Familial density of
      alcoholism predicted an earlier onset of drinking, as did having deficits in
      reading achievement, reduced P300 (visual and auditory), and greater postural
      sway for age. Higher scores on the Extraversion scale of the Junior version of
      the Eysenck Personality Inventory also predicted an earlier onset of drinking.
      CONCLUSIONS: Familial density of alcoholism (number of alcoholic first- and
      second-degree relatives) is an important predictor of adolescent alcohol
      initiation. Evidence is presented suggesting that part of the familial/genetic
      variation in outcome may be due to neurobiological factors and temperament.

PMID- 10960158
TI  - Auditory P3a assessment of male alcoholics.
AB  - BACKGROUND: P3a amplitude differences between alcoholic and control groups have
      not been well defined. Because event-related potential (ERP) differences between
      these groups appear to be influenced by task difficulty, the present study
      employed a new auditory ERP paradigm, in which target/standard tone
      discriminability was difficult, with infrequent nontarget stimuli used to elicit
      the P3a. METHODS: A total of n = 27 male alcoholics and n = 25 male controls were
      assessed using a three-tone discrimination paradigm, in which the
      discriminability between the target and standard was difficult, with easily
      discriminable infrequent nontarget tones also presented. A P3a component with a
      centro-frontal maximum to the rare nontargets and a P3b with a parietal maximum
      amplitude to the target stimulus were obtained. Current Source Density (CSD) maps
      were derived from the potential data and employed to assay topographical
      differences between subject groups. RESULTS: Alcoholics produced smaller P3a
      amplitudes than control subjects to the rare nontargets with no peak latency
      differences observed. The most prominent current sources are apparent more
      anteriorly for the nontarget compared to the target stimulus in both groups.
      There were more sources and sinks in the alcoholics than in the control subjects
      for P3a. A bootstrap analysis method showed that P3a CSD maps evinced distinct
      topographic distributions between alcoholics and control subjects in all brain
      regions. CONCLUSIONS: The lower P3a amplitude and weaker sources in alcoholics
      coupled with less topographic specificity in their CSD maps, suggests
      disorganized inefficient brain functioning. This global electrophysiological
      pattern suggests cortical disinhibition perhaps reflecting underlying CNS
      hyperexcitability in alcoholics.

PMID- 10960159
TI  - The relationship of obsessive-compulsive disorder to possible spectrum disorders:
      results from a family study.
AB  - BACKGROUND: The familial relationship between obsessive-compulsive disorder (OCD)
      and "obsessive-compulsive spectrum" disorders is unclear. This study investigates
      the relationship of OCD to somatoform disorders (body dysmorphic disorder [BDD]
      and hypochondriasis), eating disorders (e.g., anorexia nervosa and bulimia
      nervosa), pathologic "grooming" conditions (e.g., nail biting, skin picking,
      trichotillomania), and other impulse control disorders (e.g., kleptomania,
      pathologic gambling, pyromania) using blinded family study methodology. METHODS:
      Eighty case and 73 control probands, as well as 343 case and 300 control first
      degree relatives, were examined by psychiatrists or Ph.D. psychologists using the
      Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. Two
      experienced psychiatrists independently reviewed all diagnostic information and
      made final consensus diagnoses using DSM-IV criteria. RESULTS: Body dysmorphic
      disorder, hypochondriasis, any eating disorder, and any grooming condition
      occurred more frequently in case probands. In addition, BDD, either somatoform
      disorder, and any grooming condition occurred more frequently in case relatives,
      whether or not case probands also had the same diagnosis. CONCLUSIONS: These
      findings indicate that certain somatoform and pathologic grooming conditions are
      part of the familial OCD spectrum. Though other "spectrum" conditions may
      resemble OCD, they do not appear to be important parts of the familial spectrum.

PMID- 10960160
TI  - Thalamic volume in pediatric obsessive-compulsive disorder patients before and
      after cognitive behavioral therapy.
AB  - BACKGROUND: Neurobiologic abnormalities in the thalamus have been implicated in
      the pathophysiology of obsessive-compulsive disorder. We recently reported
      increased thalamic volume in treatment-naive pediatric obsessive-compulsive
      disorder patients versus case-matched healthy comparison subjects that decreased
      to levels comparable to control subjects after effective paroxetine therapy. To
      our knowledge, no prior study has measured neuroanatomic changes in the thalamus
      of obsessive-compulsive disorder patients near illness onset before and after
      cognitive behavioral therapy. METHODS: Volumetric magnetic resonance imaging
      studies were conducted in 11 psychotropic drug-naive 8-17-year-old children with
      obsessive-compulsive disorder before and after 12 weeks of effective cognitive
      behavioral therapy monotherapy (> or =30% reduction in obsessive-compulsive
      disorder symptom severity). RESULTS: No significant change in thalamic volume was
      observed in obsessive-compulsive disorder patients before and after cognitive
      behavioral therapy. CONCLUSIONS: Our findings suggest that reduction in thalamic
      volume after paroxetine therapy may be specific to paroxetine treatment and not
      the result of a general treatment response or spontaneous improvement. These
      results are preliminary in view of the small sample studied.

PMID- 10960162
TI  - Plasma adrenocorticotropin responses to opioid blockade with naloxone: generating
      a dose-response curve in a single session.
AB  - We examined two methods of generating a dose-response curve to the opioid
      receptor antagonist naloxone. In 15 healthy male subjects (18-25 years) plasma
      adrenocorticotropin (ACTH) responses to five doses of naloxone studied over 5
      separate days were compared to plasma ACTH responses to five incremental doses of
      naloxone studied within a single session. There was a statistically significant
      positive correlation in ACTH responses (area under the curve and peak) between
      dosing methods. Furthermore, the doses of naloxone that produced half-maximal and
      maximal ACTH response were similar. The comparability of ACTH responses between
      the two naloxone dosing techniques, combined with the safety and ease associated
      with the single-session methodology, underscores the usefulness of the single
      session technique for future investigations.

PMID- 10960161
TI  - Hippocampal volume in geriatric depression.
AB  - BACKGROUND: There is a growing literature on the importance of hippocampal volume
      in geriatric depression. METHODS: We examined hippocampal volume in a group of
      elderly depressed patients and a group of elderly control subjects (N = 66
      geriatric depressed patients and 18 elderly nondepressed control subjects)
      recruited through Duke's Mental Health Clinical Research Center for the Study of
      Depression in the Elderly. The subjects received a standardized evaluation,
      including a magnetic resonance imaging scan of the brain. Patients had unipolar
      major depression and were free of comorbid major psychiatric illness and
      neurologic illness. Differences were assessed using t tests and linear regression
      modeling. RESULTS: Accounting for the effects of age, gender, and total brain
      volume, depressed patients tended to have smaller right hippocampal volume (p
      =.014) and left hippocampal volume (p =.073). Among depressed patients, age of
      onset was negatively but not significantly related to right hippocampal volume (p
      =.052) and to left hippocampal volume (p =.062). We noted that among subjects
      with either right or left hippocampal volume of 3 mL or less, the vast majority
      were patients rather than control subjects. CONCLUSIONS: These results support a
      role for hippocampal dysfunction in depression, particularly in late-age onset
      depression. Longitudinal studies examining both depressive and cognitive outcomes
      are needed to clarify the relationships between the hippocampus, depression, and
      dementia.

PMID- 10960163
TI  - CSF oxytocin and vasopressin levels after recovery from bulimia nervosa and
      anorexia nervosa, bulimic subtype.
AB  - BACKGROUND: When ill, people with eating disorders have disturbances of the
      neuropeptides vasopressin and oxytocin. METHODS: To avoid the confounding effects
      of the ill state, we studied women who were recovered (more than 1 year, normal
      weight, and regular menstrual cycles, no bingeing or purging) from bulimia
      nervosa (rBN) or binge eating/purging-type anorexia nervosa (rAN-BN), and matched
      healthy control women. RESULTS: Vasopressin was elevated in rAN-BN and showed a
      trend towards elevation in rBN. In rBN, elevated cerebrospinal fluid vasopressin
      may be related to having a lifetime history of major depression. In comparison,
      cerebrospinal fluid oxytocin was normal in recovered subjects, but elevated
      levels in some rBN might be related to birth control pill use. CONCLUSIONS: These
      data confirm and extend the possibility that elevated cerebrospinal fluid
      vasopressin may be related to the pathophysiology of eating disorders, and/or a
      lifetime history of major depression.

PMID- 10960164
TI  - Possible association between serotonin transporter gene polymorphism and violent
      suicidal behavior in mood disorders.
AB  - BACKGROUND: Genes involved in the serotonin system are major candidates in
      association studies of suicidal behavior. In this case-control study we
      investigated whether the serotonin transporter (5-HTT) gene encoding the protein
      responsible for the reuptake of serotonin from the synapse after its release from
      serotonergic neurons is a susceptibility factor for suicidal behavior. METHODS: A
      functional polymorphism of the 5-HTT gene (a 44-base pair insertion/deletion in
      the 5-HTT-linked polymorphic region [5-HTTLPR]) was studied in a population of
      237 consecutive patients with affective disorder (unipolar or bipolar) and 187
      control subjects. Ninety-nine patients had attempted suicide at least once, of
      whom 26 made a violent attempt. RESULTS: No association was found between the "s"
      allele of the 5-HTTLPR and suicide attempt; however, there was a significant
      difference in allele distributions between patients who had made violent suicide
      attempts and control subjects. CONCLUSIONS: A genetic variant of the 5-HTT gene
      may predispose individuals to violent suicidal behavior. The precise phenotype
      associated with the 5-HTT gene is unclear, and therefore further studies are
      required to replicate these findings.

PMID- 10960166
TI  - Tryptophan depletion and risk of depression relapse: a prospective study of
      tryptophan depletion as a potential predictor of depressive episodes.
AB  - BACKGROUND: This study investigated the relationship between depressive symptom
      response during tryptophan depletion and future depressive episodes. METHODS:
      Twelve subjects with prior major depressive episodes in remission and medication
      free for > or =3 months (patients), and 12 matched healthy (control) subjects
      received two tryptophan depletion tests 1 week apart. During follow-up the
      Hamilton Depression Rating Scale was administered weekly for 1 month, monthly for
      3 months, and once at 6 and 12 months. RESULTS: With results from both tests,
      tryptophan depletion has a sensitivity of 78%, specificity of 80%, positive
      predictive value of 70%, and negative predictive value of 86% to identify future
      depressive episodes. Survival analysis shows that mood response to tryptophan
      depletion reliably predicts major depressive episodes during the follow-up year
      (r =.2725, p =.014). CONCLUSIONS: Tryptophan depletion may be clinically useful
      in identifying individuals at risk for future major depressive episodes.

PMID- 10960165
TI  - Thyroid function and response to 48-hour sleep deprivation in treatment-resistant
      depressed patients.
AB  - BACKGROUND: Clinical depression is associated with abnormalities of the
      hypothalamic-pituitary-thyroid axis. Changes in thyroid function during sleep
      deprivation may be related to its antidepressant effects. METHODS: Levels of
      thyroid-stimulating hormone, tri-iodothyronine, tri-iodothyronine uptake,
      thyroxine, and free thyroxine were measured before, during, and after a 48-hour
      sleep deprivation in nine treatment-resistant depressed patients. Clinical state
      was assessed every 4 hours. A retrospective study of 26 similar patients was
      added for cross-validation. RESULTS: Significant increases in thyroid-stimulating
      hormone and tri-iodothyronine during sleep deprivation were not correlated with
      clinical improvement. Sleep deprivation responders had lower tri-iodothyronine
      uptake levels than nonresponders in both the prospective (p <.02) and the
      retrospective (p <.03) samples. CONCLUSIONS: The lower tri-iodothyronine uptake
      values in responders may identify a subgroup of depressed patients who respond to
      sleep deprivation by virtue of some abnormality of the hypothalamic-pituitary
      thyroid axis that is temporarily corrected by sleep deprivation.

PMID- 10960167
TI  - Vasopressin, major depression, and hypothalamic-pituitary-adrenocortical
      desensitization.
AB  - BACKGROUND: The hypothalamic neuropeptide arginine vasopressin is thought to play
      an important role in the pathophysiology of affective disorders and the
      hyperactivity of the hypothalamic-pituitary-adrenocortical system that frequently
      accompanies them. Postmortem studies as well as clinical investigations have
      described elevated levels of vasopressin in the brain and plasma of depressed
      patients, and this finding has been suggested to contribute to depressive
      symptomatology. METHODS: The case of a 47-year-old patient displaying chronically
      elevated plasma vasopressin levels due to paraneoplastic vasopressin secretion by
      an olfactory neuroblastoma and the first episode of major depression is
      presented. RESULTS: Depressive symptoms improved markedly after surgical
      resection of the tumor and subsequent normalization of plasma vasopressin levels.
      Unexpectedly, neither corticotropin nor cortisol secretion could be stimulated by
      an intravenous corticotropin-releasing hormone challenge under the condition of
      chronically elevated plasma vasopressin levels in this patient. CONCLUSIONS:
      Chronically elevated plasma vasopressin levels may induce depressive
      symptomatology, and-in contrast to the potent corticotropin secretagogue effects
      of acute vasopressin administration-lead to a marked desensitization of the
      hypothalamic-pituitary-adrenocortical system.

PMID- 10960169
TI  - Identification of a stress-responsive Onchocerca volvulus glutathione S
      transferase (Ov-GST-3) by RT-PCR differential display.
AB  - The effects of oxidative insult on gene transcript levels in the filarial
      nematode Onchocerca volvulus were investigated using differential display RT-PCR.
      Oxidative stress was applied with the reagents paraquat, plumbagin and xanthine
      xanthine oxidase. In all three cases, a cDNA fragment encoding a novel
      glutathione S-transferase (GST) resembling members of the theta-class was
      identified as upregulated (PQ29, PG112, XOD26). The subsequently isolated full
      length cDNA harbors a 753-bp open reading frame encoding a GST with 268 amino
      acid residues and a predicted molecular mass of 31 kDa. This stress-responsive
      GST (Ov-GST-3) possesses only 14 and 21% sequence identity with the other O.
      volvulus GSTs (Ov-GST-1 and Ov-GST-2, respectively). Interestingly, Ov-GST-3
      shares higher sequence identity with GSTs that are upregulated due to
      environmental stress. In order to confirm the specific upregulation of the Ov-GST
      3 transcripts identified by differential display and to analyze the mRNA levels
      of the other Ov-GSTs (Ov-GST-1 and Ov-GST-2) under elevated stress conditions, a
      semi-quantitative polymerase chain reaction-enzyme-linked immunosorbent assay was
      performed. The Ov-GST-3 gene transcript level increased dramatically in response
      to xanthine-xanthine oxidase and to a lesser extent with paraquat and plumbagin.
      In contrast, Ov-GST-1 and Ov-GST-2 did not show any significant alterations in
      their steady-state mRNA levels in response to oxidative stress when examining the
      same mRNA samples. The present study clearly demonstrates that Ov-GST-3 is a
      critical enzyme in the defense against oxidative stress.

PMID- 10960168
TI  - Angiogenic activity of Onchocerca volvulus recombinant proteins similar to vespid
      venom antigen 5.
AB  - Although the mechanisms underlying the host inflammatory response in ocular
      onchocerciasis have been examined, the role of particular parasite proteins in
      this process remains largely unexplored. Recently, it was found that one of the
      most abundant expressed sequence tags in Onchocerca volvulus infective larvae
      encoded a protein with similarities to a component of vespid venom. This clone
      was designated O. volvulus Activation associated Secreted Protein -1 (Ov-asp-1).
      We report the characterization of three members of a family of proteins,
      designated the Ov-ASP family, of which Ov-ASP-1 is a member. Sequence based and
      phylogenetic analyses suggest that these proteins form a filarial specific
      protein family related to both the vespid venom antigen 5 and the vertebrate
      CRISP/Tpx family of proteins. The three members of the Ov-ASP family exhibit
      distinct patterns of expression in the life cycle of O. volvulus. Genomic
      Southern blot analyses indicate that several genes encoding sequences related to
      the Ov-asp family are present in the genome of O. volvulus. Recombinant proteins
      expressed from full length cDNAs encoding two members of the Ov-asp family were
      found to induce an angiogenic response after injection into corneas of naive
      mice, and vessel formation was associated with only minor inflammatory cell
      infiltration. These data suggest that Ov-ASP proteins may directly induce an
      angiogenic response and may therefore contribute to corneal neovascularization in
      onchocercal keratitis.

PMID- 10960170
TI  - Intragenic recombination in the 3' portion of the merozoite surface protein 1
      gene of Plasmodium vivax.
AB  - To date, little has been known about the extent of sequence variation in the C
      terminal part of the Plasmodium vivax merozoite surface protein 1 (PvMSP1) which
      has been considered to be a potential vaccine candidate. Here, we examined the
      variation in the region encompassing interspecies conserved blocks (ICBs) 8 and
      10 of PvMSP1 by DNA sequencing of 14 Thai isolates and three Brazilian isolates.
      Eighteen different alleles were detected. Three new sequence types had been
      identified in polymorphic region between ICB8 and CB9: one was possibly a result
      of intragenic recombination between the Belem and Salvador I alleles and the
      others displayed unique repeats. A striking variation was observed in a stretch
      of 38 codons in polymorphic block between conserved block CB9 and ICB10,
      resulting in eight different sequence types, probably generated by interallelic
      recombination at a single or multiple sites. There is no apparent linkage between
      these two polymorphic sites. On the other hand, a single or stretches of
      nucleotide substitutions are dimorphic like in Plasmodium falciparum MSP1
      (PfMSP1) in the remaining parts, creating microheterogeneity of sequences. The C
      terminal 19 kDa-encoding region was extremely conserved with a single dimorphic
      exchange at a known position. Thus, this study provides evidence of intragenic
      recombination occurring in the 3' portion of PvMSP1 and suggests that the 3'
      portion of PvMSP1 is more diverse than that in PfMSP1.

PMID- 10960171
TI  - Two genes encoding unique proliferating-cell-nuclear-antigens are expressed in
      Toxoplasma gondii.
AB  - Complete cDNA sequences encoding two novel proliferating-cell-nuclear-antigens
      (designated TgPCNA1 and 2) were isolated from a Toxoplasma gondii tachyzoite cDNA
      library, and Southern analysis using cDNA probes confirmed the presence of two
      PCNA genes in T. gondii genomic DNA. Expressed-sequence-tags were identified in
      the T. gondii database that matched each TgPCNA cDNA and closely related PCNA
      coding regions (designated PfPCNA1 and 2) were discovered in sequence data
      obtained from chromosome 12 and 13 of Plasmodium falciparum. TgPCNA1 and PfPCNA1
      were found to share the highest amino acid identity at 49% compared to TgPCNA2
      and PfPCNA2 (37% identity) whereas intraspecies PCNAs were determined to be less
      similar (27-30% identity). Phylogenetic analysis suggests the two apicomplexan
      PCNAs are the result of a gene duplication in the common ancestor of these
      parasites. Antibodies specific for TgPCNA1 ( approximately 40 kDa) or TgPCNA2 (
      approximately 37 kDa) detected single antigen species in tachyzoite extracts that
      were expressed at similar levels in isolates representative of the T. gondii Type
      I, II and III strains. TgPCNA1-specific cDNA probes detected multiple mRNA
      species on Northern blots, which when combined, were expressed 5-7 fold higher
      than the single species of mRNA detected by the TgPCNA2 probe. The difference in
      the number of mRNA species and comparative mRNA levels suggests each TgPCNA gene
      is independently controlled, although in light of the nearly equal levels of
      protein a post-transcriptional mechanism may be responsible for equalizing
      protein expression.

PMID- 10960172
TI  - Tandemly repeated DNA is a target for the partial replacement of thymine by beta
      D-glucosyl-hydroxymethyluracil in Trypanosoma brucei.
AB  - In the DNA of African trypanosomes a small fraction of thymine is replaced by the
      modified base beta-D-glucosyl-hydroxymethyluracil (J). The function of this large
      base is unknown. The presence of J in the silent variant surface glycoprotein
      gene expression sites and the lack of J in the transcribed expression site
      indicates that DNA modification might play a role in control of gene repression.
      However, the abundance of J in the long telomeric repeat tracts and in
      subtelomeric arrays of simple repeats suggests that J may also have specific
      functions in repetitive DNA. We have now analyzed chromosome-internal repetitive
      sequences in the genome of Trypanosoma brucei and found J in the minichromosomal
      177-bp repeats, in the long arrays of 5S RNA gene repeats, and in the spliced
      leader RNA gene repeats. No J was found in the rDNA locus or in dispersed
      repetitive transposon-like elements. Remarkably, the rDNA of T. brucei is not
      organized in long arrays of tandem repeats, as in many other eukaryotes. T.
      brucei contains only approximately 15-20 rDNA repeat units that are divided over
      six to seven chromosomes. Our results show that J is present in many tandemly
      repeated sequences, either at a telomere or chromosome internal. The presence of
      J might help to stabilize the long arrays of repeats in the genome.

PMID- 10960174
TI  - Isolation and characterisation of a cAMP-dependent protein kinase catalytic
      subunit gene from Plasmodium falciparum.

PMID- 10960173
TI  - Molecular characterisation of Plasmodium reichenowi apical membrane antigen-1
      (AMA-1), comparison with P. falciparum AMA-1, and antibody-mediated inhibition of
      red cell invasion.
AB  - Apical membrane antigen 1 is a candidate vaccine component for malaria. It is
      encoded by a single copy gene and has been characterised in a number of malaria
      species as either an 83-kDa de novo product (Plasmodium falciparum; Pf AMA-1) or
      a 66-kDa product (all other species). All members of the AMA-1 family are
      expressed during merozoite formation in maturing schizonts and are initially
      routed to the rhoptries. Processed forms may subsequently be associated with the
      merozoite surface. Because of the unique occurrence of the 83-kDa form in P.
      falciparum we were interested to determine whether the phylogenetically closely
      related chimpanzee malaria Plasmodium reichenowi shared characteristics with Pf
      AMA-1. Here we show that the molecular structure, the localisation and processing
      are similar to that of Pf AMA-1 and that in vitro growth inhibitory mAbs reactive
      with Pf AMA-1 also inhibit P. reichenowi growth in an in vitro assay.
      Polymorphism in the 83-kDa AMA-1 family was analysed through comparison of Pr ama
      1 with Pf ama-1 alleles, which showed the most significant evidence for selection
      maintaining polymorphism in Domains I-III of AMA-1 in P. falciparum. The most
      substantial divergence between Pr AMA-1 and Pf AMA-1 sequences was in the N
      terminal region unique to the 83-kDa form of AMA-1. It was confirmed that the
      specific Pr ama-1-type allele was not present among P. falciparum parasites in an
      African population, and an allele coding for lysine at amino acid 187 was
      uniquely associated with field isolates in this population.

PMID- 10960175
TI  - Molecular cloning and characterization of a peroxiredoxin from the human malaria
      parasite Plasmodium falciparum.

PMID- 10960176
TI  - Characterization of the N-linked glycans of adult Trichinella spiralis.

PMID- 10960177
TI  - Expression, purification and characterization of a functional region of the
      Plasmodium vivax Duffy binding protein.

PMID- 10960178
TI  - Allelic lineages of the merozoite surface protein 3 gene in Plasmodium reichenowi
      and Plasmodium falciparum.

PMID- 10960179
TI  - Antigens cross reactive with Plasmodium falciparum merozoite surface protein 4
      are found in pre-erythrocytic and sexual stages.

PMID- 10960181
TI  - Hydrophobicity: is LogP(o/w) more than the sum of its parts?
AB  - The empirically calculated parameter LogP(o/w), the log(10) of the coefficient
      for solvent partitioning between 1-octanol and water, has been used to provide
      the key data for a unique non-covalent interaction force field called HINT
      (Hydropathic INTeractions). This experimentally-derived force field encodes
      entropic as well as enthalpic information and also includes some representation
      of solvation and desolvation energetics in biomolecular associations. The
      theoretical basis for the HINT model is discussed. This review includes: 1)
      discussion of calculational representation of the hydrophobic effect, 2) the
      rationale for describing the experimental LogP(o/w) based descriptors used in the
      HINT force field and model as free energy-like, 3) the relationship between
      hydrophobic fragment constants and partial group electrostatic charge, and 4) the
      implications of structurally-conserved water molecules on free energy of
      molecular association. Several recent applications of HINT in structure-based and
      ligand-based drug discovery are reviewed. Finally, future directions in the HINT
      model development are proposed.

PMID- 10960180
TI  - Calmodulin-binding properties of the paraflagellar rod complex from Trypanosoma
      brucei.

PMID- 10960182
TI  - Design and synthesis of substituted compounds containing the 1, 4-benzodioxin
      subunit. New potential calcium antagonists.
AB  - New compounds possessing 1,4-benzodioxin or its saturated analogous heterocyclic
      system were synthesized and tested for calcium antagonist activity. Biological
      differences were seen between the different modifications applied. These
      compounds have been shown to be representative of a novel series of calcium
      channel antagonists.

PMID- 10960183
TI  - High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3
      d]pyrimidinone derivatives for the 5-HT(1A) receptor. Synthesis and structure
      affinity relationships.
AB  - In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and
      the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1
      piperazinyl]propyl]thio]-6-ethyl -thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most
      potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4
      piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows
      a good affinity and selectivity (Ki 1. 46 nM, selectivity 84). The results of
      derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5,
      respectively), which have, respectively, an ethyl, an allyl and an acetylamino
      group instead of an N3 amino group, indicate the importance of this last group
      for the interaction with 5-HT(1A)R. Comparison of the results for the superior
      homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT(1A)
      Ki 1499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]
      6,7-dimethyl-8H-[1, 3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23
      nM, selectivity 5) shows how important the length of the chain binding the two
      heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs.

PMID- 10960184
TI  - Synthesis and antineoplastic activity of cyclolignan aldehydes.
AB  - Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a
      selective antitumour agent against the HT-29 colon carcinoma, have been prepared
      and evaluated for their cytotoxic activities on four neoplastic cell lines (P
      388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained
      their cytotoxicity at, or under, the microM level.

PMID- 10960185
TI  - Synthesis and preliminary pharmacological results on new naphthalene derivatives
      as 5-HT(4) receptor ligands.
AB  - The indole derivative GR 113808 is currently used as the reference ligand for
      labelling the 5-HT(4) serotoninergic receptors. Previous works in our
      laboratories established the bioisosteric equivalency of the indole heterocycle
      and naphthalene in a series of melatonin receptor ligands. Based on this
      knowledge we designed new analogues of GR 113808 by introducing two bioisosteric
      modifications: firstly, the indole ring was replaced by a naphthalene one and
      secondly, the ester linkage was replaced by an amide group. Compound 8 emerged
      within this novel series as it displayed high and selective affinity at 5-HT(4)
      receptors (Ki 5-HT(4) = 6 nM, Ki 5-HT(3) = 100 nM, Ki values at other 5-HT
      receptors were higher than 1000 nM). Compound 8 is currently undergoing further
      pharmacological evaluation.

PMID- 10960186
TI  - Synthetic ferrocenic mefloquine and quinine analoguesas potential antimalarial
      agents.
AB  - A few years ago we proposed a strategy for the synthesis of new ferrocene
      chloroquine analogues replacing the carbon chain of chloroquine by hydrophobic
      ferrocenyl moieties. Now, this strategy has been applied to the antimalarial
      amino-alcohols class to afford new potentially active analogues of mefloquine and
      quinine bearing a substituted ferrocenic group. The pathway used for the
      synthesis of the mefloquine analogues includes the coupling of an aminomethyl
      substituted ferrocene carboxaldehyde with a lithio quinoline compound. On the
      other hand, the synthesis of quinine analogues was ensured by the 'inverse'
      reaction of a lithio aminomethyl ferrocene with a quinoline carboxaldehyde. The
      configurations of each diastereoisomer were unambiguously determined by
      spectroscopic data. The mechanistic interpretations were fully discussed.
      Ferrocenyl analogues of mefloquine and quinine exhibited a lower antimalarial
      activity than mefloquine and quinine themselves. Comparing optical isomers, those
      isomers dissimilar to ferrocenyl derivatives presented better antimalarial
      activities than those similar to ferrocenyl.

PMID- 10960187
TI  - 5-(4'-Substituted-2'-nitroanilino)-1,2,3-triazoles as new potential potassium
      channel activators. I.
AB  - By the hypothesised correlation with the large conductance Ca(++)-activated
      potassium channel (BK(Ca)) openers NS 004 and NS 1619, bearing a benzimidazolone
      ring, a series of new 5-(4'-substituted-2'-nitroanilino)-1,2,3-triazoles were
      synthesised and tested on in vitro isolated vascular preparation. The compounds
      were prepared starting from the appropriately substituted 2-nitro-phenylazides by
      1,3-dipolar cycloaddition reaction to cyanoacetamide and following Dimroth
      isomerisation of the corresponding 1-arylsubstituted-5-amino-1,2,3-triazoles. The
      analogous 5-(4'-substituted-2'-amino-anilino)-1,2,3-triazoles were also prepared
      to assess the role of the nitro group in the pharmacophoric model. Almost all the
      nitro compounds showed a vasorelaxant activity on endothelium-denuded rat aortic
      rings with a potency comparable to that recorded for the reference compound NS
      1619. Such a vasorelaxing activity was significantly reduced by the increase of
      the level of membrane depolarisation and by the potassium channel blocker 4
      aminopyridine with a pharmacodynamic behaviour consistent with a potassium
      channel activation.

PMID- 10960188
TI  - Non-thiol farnesyltransferase inhibitors: the concept of benzophenone-based
      bisubstrate analogue farnesyltransferase inhibitors.
AB  - Replacement of the thiol in a benzophenone-based CAAX-peptidomimetic
      farnesyltransferase inhibitor by a carboxylic acid moiety resulted in a marked
      drop in inhibitory potency. Transformation of these carboxylic acid derivatives
      into bisubstrate analogues by addition of a lipophilic alkyl chain, which should
      be able to occupy considerable portions of the farnesyl binding region in the
      farnesyltransferase's active site, resulted in a regain of the inhibitory
      activity. These bisubstrate analogues represent new lead structures for non-thiol
      farnesyltransferase inhibitors.

PMID- 10960189
TI  - Synthesis and structure-activity of antisense peptides corresponding to the
      region for CaM-binding domain of the inducible nitric oxide synthase.
AB  - Nitric oxide synthase (NOS) catalyses the conversion of L-arginine to nitric
      oxide (NO) which plays an important role in the regulation of cellular functions
      and intracellular communications. Three distinct isoforms of NOS have so far been
      identified, two constitutive and one inducible. All three mammalian isoforms of
      NOS contain putative CaM-binding domains with the canonical composition. In this
      paper we report the synthesis and the inhibitory activity on rat neuronal and
      lung inducible NOS of antisense peptides corresponding to the antisense strand
      read in 3' to 5' (CALM 1) or 5' to 3' (CALM 2) direction of the region encoding
      for the CaM-binding domain of the inducible NOS isoform (residues 503-522). CALM
      1 inhibited, at all the concentrations tested (0.01-1 mM), both the inducible and
      constitutive NOS (IC(50) 98 microM and 56 microM, respectively), while CALM 2
      (0.01-1 mM) was ineffective on both isoforms. The acetylation of CALM 1 at its
      amino terminal (CALM 8) completely abolished its inhibitory activity. We also
      synthesized and analysed the activity of amino terminal truncated analogues (CALM
      3-7) of CALM 1, which selectively inhibited the inducible isoform, although less
      potently than the parent compound. The pentapeptides (CALM A-D) deriving from the
      cleavage of CALM 1 were ineffective, except the pentapeptide CALM C corresponding
      to the residues 513-517, which was as potent as the parent compound (IC(50) 65
      microM).

PMID- 10960190
TI  - New groups of antimycobacterial agents: 6-chloro-3-phenyl-4-thioxo-2H-1,3
      benzoxazine-2(3H)-ones and 6-chloro-3-phenyl-2H-1,3-benzoxazine-2,4(3H)
      dithiones.
AB  - A series of 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones 3 and a
      series of 6-chloro-3-phenyl-2H-1,3-benzoxazine-2, 4(3H)-dithiones 4 were
      synthesized by melting 6-chloro-3-phenyl-2H-1, 3-benzoxazine-2,4(3H)-dione and
      its derivatives substituted on the phenyl ring 2 with tetraphosphorus
      decasulfide. Compounds 2c-e, 3 and 4 exhibited in vitro activity against
      Mycobacterium tuberculosis, M. kansasii (two strains) and M. avium better than or
      comparable to that of isoniazid. Replacement of the oxo group by a thioxo group
      at position 4 led to improvement in activity against M. tuberculosis and M.
      kansasii. The Free-Wilson method and procedure developed by the authors were used
      to analyse the structure-activity and structure-antimycobacterial profile
      relationships, respectively.

PMID- 10960191
TI  - 6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones substituted withibuprofen:
      synthesis, characterization and evaluation of anti-inflammatory activity.
AB  - In this study, the synthesis of 3-[1-(4-(2-methylpropyl)phenyl)ethyl]-1,2,4
      triazole-5-thione (2) and its condensed derivatives 6-benzylidenethiazolo[3,2-b]
      1,2, 4-triazole-5(6H)-ones (2a-u) are described. The structures of the compounds
      were elucidated by spectral and elemental analysis. In the pharmacological
      studies, anti-inflammatory activities of these compounds have been screened.
      Among the compounds examined, the compounds 2 and 2g possessed the most prominent
      and consistent activity. In gastric ulceration studies the synthesized compounds
      were generally found to be safe at a 200 mg/kg dose level.

PMID- 10960192
TI  - Synthesis and pharmacological evaluation of 2, 3-dihydro-3-oxo-4H-thieno[3,4
      e][1,2,4]thiadiazine 1,1-dioxides as voltage-dependent calcium channel blockers.
AB  - The synthesis of a novel series of 2,3-dihydro-3-oxo-4H-thieno[3, 4
      e][1,2,4]thiadiazine 1,1-dioxides and their pharmacological evaluation as drugs
      with effects on the rat cardiovascular system are described. The compounds under
      study were synthesized via Curtius rearrangement of appropriate
      sulfamoylacylazides which, in turn, were prepared from known starting materials.
      In isolated rat portal vein, these thienothiadiazines, like verapamil and
      diazoxide, inhibited the spontaneous motility produced by KCl (20 mM). In
      addition, the new compounds, like verapamil and unlike diazoxide, also exhibited
      inhibitory effects in the same preparation when the cell membrane was depolarized
      by an increased extracellular KCl concentration (80 mM) and, consequently, the
      membrane potential approached a level close to the K(+) equilibrium potential.
      Further characterization of this inhibitory activity led to the identification of
      a selective inhibitory effect of the new compounds on KCl (80 mM)-induced
      45Ca(2+) uptake in the same vascular tissue. When tested in vivo (anaesthetized
      normotensive rats), acute administration of verapamil, diazoxide and some of the
      most in vitro potent compounds in 45Ca(2+) uptake experiments produced a gradual,
      dose-dependent and sustained decrease in diastolic arterial blood pressure,
      devoid of cardiac effects. These results suggest that, like verapamil, the
      cardiovascular effects produced by the new thienothiadiazines seem to be due, at
      least in part, to a blockade of transmembrane voltage-dependent calcium channels
      present in vascular smooth muscle cells and not to an activation of ATP-sensitive
      K(+) channels. Compounds 5b, 5e and 5i have been selected for further studies as
      antihypertensive agents.

PMID- 10960193
TI  - Synthesis, characterization and pharmacological properties of some 4
      arylhydrazono-2-pyrazoline-5-one derivatives obtained from heterocyclic amines.
AB  - The synthesis of a new series of 4-arylhydrazono-2-pyrazoline-5-ones 7-24 and 22a
      is described. Structures of the synthesized compounds were confirmed using UV,
      IR, 1H-NMR, 13C-NMR and EI-mass spectral data. These compounds were tested in
      vitro against one Gram-positive and two Gram-negative bacterial strains, two
      mycobacterial strains and a fungus, Candida albicans. Compound 22 was found to be
      more active against Staphylococcus aureus than the other compounds at a
      concentration of 15.6 microg/mL. Some related compounds were evaluated for
      anticonvulsant activity. Compound 11 showed 40% protection against
      pentylenetetrazole-induced seizures in albino Swiss mice. In vitro
      antituberculosis activity of 4-arylhydrazono-2-pyrazoline-5-ones 7-12, 14-24, 22a
      and coupling products 6a-f were tested on Mycobacterium tuberculosis H37Rv. Of
      these compounds, only 24, which exhibited > 90% inhibition in the primary screen
      at 12.5 microg/mL against this strain was re-examined for determination of its
      actual MIC. However, level II assay revealed that the MIC value was not less than
      12.5 microg/mL. The same compound was also tested against Mycobacterium avium,
      which was observed not to be susceptible to 24.

PMID- 10960194
TI  - Synthesis and alpha(1)-antagonist activity of derivatives of 4-chloro-5-[4-[2-(2
      methoxyphenoxy)-ethyl]-1-piperazinyl]-3(2H)-pyrid azinone.
AB  - The synthesis and evaluation of the biological activity of new 4-chloro-5-?4-[2
      (2-methoxyphenoxy)-ethyl]-1-piperazinyl?-3(2H)-pyrid azinone derivatives are
      reported. The blocking activity of these compounds was determined on the pre- and
      postsynaptic alpha-adrenoceptors of isolated rat vas deferens.

PMID- 10960195
TI  - Myths in anesthesiology.

PMID- 10960196
TI  - The use of propofol for its antiemetic effect: a survey of clinical practice in
      the United States.
AB  - STUDY OBJECTIVES: To investigate the use of propofol by anesthesiologists for its
      antiemetic effect and to compare our findings with published evidence. DESIGN:
      Anonymous survey of U.S. anesthesiologists. SETTING: American Society of
      Anesthesiologists' annual meeting. MEASUREMENTS AND MAIN RESULTS: One hundred
      fifty anesthesiologists were surveyed on how they use propofol to achieve an
      antiemetic effect. A large majority (84%) of the anesthesiologists surveyed
      stated they used propofol for its antiemetic effect: 63% of those used propofol
      for induction only for cases lasting <1 h to achieve an antiemetic effect. In
      addition 37% used a "sandwich" technique, using propofol at the beginning and end
      of a case for a similar purpose. There is evidence that the antiemetic effect of
      propofol is associated with a defined plasma concentration range; mean, 343 ng/mL
      (10-90% confidence intervals [CI] 200-600 ng/mL). Simulation data demonstrated
      that after propofol 2 mg/kg, its concentration will drop below 350 ng/mL at 32
      min. After 2 mg/kg and 20 mg within 10 min of the end of surgery, its
      concentration will drop below 350 ng/mL by 7 min after the 20 mg bolus dose. This
      finding suggests that the plasma concentrations of propofol, when used in these
      cases, will be below the effective range of antiemetic effect. CONCLUSIONS: Many
      anesthesiologists used propofol for its antiemetic effect. There is strong
      evidence for its antiemetic efficacy after anesthesia maintained by a propofol
      infusion and also for its use in the postanesthesia care unit (PACU). However,
      there is little evidence to support its use purely at induction of anesthesia or
      as part of a "sandwich" technique in an attempt to reduce postoperative nausea
      and vomiting. This is especially true in cases lasting longer than a few minutes.

PMID- 10960197
TI  - Measurement of coronary sinus flow using transesophageal echocardiography in
      patients undergoing coronary artery bypass grafting.
AB  - STUDY OBJECTIVE: To measure coronary sinus blood flow during coronary artery
      bypass graft (CABG) with transesophageal echocardiography (TEE). DESIGN:
      Prospective study. SETTING: Elective cardiac surgery at a university hospital.
      PATIENTS: Thirty-one ASA physical status III and IV adult patients free of
      significant coexisting disease and undergoing CABG. INTERVENTION: We measured
      coronary sinus blood flow velocity by using TEE and hemodynamic variables, before
      and after cardiopulmonary bypass (CPB) and after CPB. MEASUREMENTS AND MAIN
      RESULTS: We obtained a complete set of control measurements for 29 subjects (94%)
      and a complete set of post-CPB measurements in 28 patients (90%). In the normal
      group, peak velocity, and velocity time integral (VTI) of coronary sinus blood
      flow in the post-CPB period increased significantly compared with the pre-CPB
      period with CABG (n = 23). In the group of new regional wall motion abnormalities
      in the post-CPB period, peak velocity and VTI of coronary sinus blood flow in the
      post-CPB period did not increase significantly compared with the pre-CPB period
      by CABG (n = 5). CONCLUSIONS: We were able to measure the coronary sinus flow
      velocity by pulse-Doppler TEE during CABG. The peak velocity and VTI of coronary
      sinus blood flow in the post-CPB period increased significantly compared with in
      the pre-CPB period by CABG. The results of this preliminary study show the
      feasibility of clinical evaluation of CABG intraoperatively.

PMID- 10960198
TI  - Quantitative description of the workload associated with airway management
      procedures.
AB  - STUDY OBJECTIVES: To measure the workload associated with specific airway
      management tasks. SETTING AND INTERVENTION: Written survey instrument. PATIENTS:
      166 Stanford University and 75 University of California, San Diego, anesthesia
      providers. MEASUREMENTS AND MAIN RESULTS: Subjects were asked to use a seven
      point Likert-type scale to rate the level of perceived workload associated with
      different airway management tasks with respect to the physical effort, mental
      effort, and psychological stress they require to perform in the typical clinical
      setting. The 126 subjects completing questionnaires (overall 52% response rate)
      consisted of 43% faculty, 26% residents, 23% community practitioners, and 8%
      certified registered nurse-anesthetists (CRNAs). Faculty physicians generally
      scored lower workload measures than residents, whereas community practitioners
      had the highest workload scores. Overall, workload ratings were lowest for
      laryngeal mask airway (LMA) insertion and highest for awake fiberoptic
      intubation. Airway procedures performed on sleeping patients received lower
      workload ratings than comparable procedures performed on awake patients. Direct
      visualization procedures received lower workload ratings than fiberoptically
      guided procedures. CONCLUSIONS: These kinds of data may permit more objective
      consideration of the nonmonetary costs of technical anesthesia procedures. The
      potential clinical benefits of the use of more complex airway management
      techniques may be partially offset by the impact of increased workload on other
      clinical demands.

PMID- 10960199
TI  - Warmed humidified inspired oxygen accelerates postoperative rewarming.
AB  - STUDY OBJECTIVE: To investigate the efficacy of warmed, humidified inspired
      oxygen (O(2)) for the treatment of mildly hypothermic postoperative patients.
      DESIGN: Prospective, randomized, unblinded clinical trial. SETTING:
      Postanesthesia care unit in a tertiary care hospital. PATIENTS AND INTERVENTIONS:
      30 ASA physical status I, II, and III patients following intraabdominal surgical
      procedures were randomly assigned to receive either routine O(2) therapy (control
      group, n = 15), or warmed (42 degrees C) humidified O(2) (treatment group, n =
      15) for the initial 90 postoperative minutes. MEASUREMENTS: Core (tympanic)
      temperature, dry mouth score and shivering score. MAIN RESULTS: Tympanic
      temperature was similar in both groups on admission ( approximately 35.8 degrees
      C). Rewarming rate in the first postoperative hour was greater in the treatment
      group (0.7 +/- 0.1 degrees C. hr(-1)) compared to the control group (0.4 +/- 0.1
      degrees C. hr(-1)) (p = 0.03). Patients receiving the warmed, humidified O(2) had
      a lower incidence of dry mouth compared to the control group (p = 0.03). The
      incidence of shivering was low and similar in both groups. CONCLUSIONS: Warming
      and humidifying inspired O(2) hastens recovery from hypothermia in postoperative
      patients.

PMID- 10960200
TI  - Relationship between clinical history, coagulation tests, and perioperative
      bleeding during tonsillectomies in pediatrics.
AB  - STUDY OBJECTIVE: To determine the value of clinical history and preoperative
      coagulation tests. DESIGN: Prospective, multicenter clinical investigation.
      SETTING: Twenty-four centers over a one-year period. PATIENTS: 1,706 children
      scheduled for tonsillectomy. In 1, 479 out of 1,706 children, studied age was
      ranged from 9 months to 15 years. Indications for surgery were tonsillar
      infection 54%, sleep apnea 33%, or both 13%. Surgical dissection was performed in
      1, 284 cases (88%) and sluder technique in 172 cases (12%). MEASUREMENTS AND MAIN
      RESULTS: Clinical history of bleeding, preoperative coagulation tests, and
      perioperative bleeding were recorded. Clinical history of bleeding was positive
      in 13 patients; clinical history cannot predict abnormal coagulation tests.
      Coagulation tests were abnormal in 57 children (4%). Only 8 patients had disease
      induced bleeding; five children had a preoperative correction of the deficiency
      in factor of coagulation or received desmopressin acetate prior to surgery in the
      case of von Willebrand's disease. Bleeding that occurred during the
      intraoperative period was assessed as abnormal by the surgeon in 101 children
      (7%) and during the postoperative period in 50 children (3%). Univariate analysis
      showed a relationship between intraoperative bleeding and age (p < 0.001), sluder
      technique (p < 0. 001), and abnormal preoperative coagulation tests (p < 0.05).
      Multivariate analysis showed the probability that bleeding was linked to the
      center where the surgery took place, the technique used, i.e., sluder technique,
      and the child's age, i.e., the older children. CONCLUSIONS: Preoperative
      assessment based on the history of bleeding cannot predict abnormal laboratory
      tests. Neither the history of bleeding or laboratory tests can predict
      postoperative bleeding.

PMID- 10960201
TI  - 0.2% ropivacaine with or without fentanyl for patient-controlled epidural
      analgesia after major abdominal surgery: a double-blind study.
AB  - STUDY OBJECTIVE: To evaluate the effects of adding low concentration of fentanyl
      to 0.2% ropivacaine when providing patient-controlled epidural analgesia (PCEA)
      outside the Post-Anesthesia Care Unit. DESIGN: Prospective, randomized, double
      blind study. SETTING: Inpatients at a University Department of Anesthesia.
      PATIENTS: 32 ASA physical status I, II, and III patients, who were scheduled for
      elective major abdominal surgery, including bowel resection, hepatic resection,
      and pancreaticoduodenectomy. INTERVENTIONS: Patients received standard
      general/epidural anesthesia. After surgery patients were randomly allocated in a
      double-blind fashion to receive PCEA with either 0.2% ropivacaine (n = 16) or
      0.2% ropivacaine/2 microg/mL fentanyl (n = 16) [background infusion ranging
      between 4 and 6 mL/hr, with 1.5-mL incremental doses and a 20-min lock-out time].
      Dynamic pain during coughing, sedation, pulse oxymetry, hemodynamic variables,
      and motor block were evaluated at 1, 6, 12, 24, and 48 hours after the end of
      surgery by a blinded observer. Occurrence of untoward events, including nausea,
      vomiting, pruritus, need for supplemental oxygen (for SpO(2) < 90%), and
      respiratory complications, as well as total consumption of PCEA solution and
      incremental doses given to the patient were also recorded. MEASUREMENTS AND MAIN
      RESULTS: No differences in pain relief, motor block, degree of sedation, recovery
      of gastrointestinal motility, and other side effects were observed between the
      two groups. Patients receiving 0.2% ropivacaine alone requested far more
      incremental doses (23 doses [0-60] vs. 5 doses [0-25]) (p = 0.006) and needed far
      more analgesic solution (230 mL [140-282] vs. 204 [130-228]) (p = 0.003) than
      patients receiving the ropivacaine/fentanyl mixture. Peripheral oxygen saturation
      was lower at 12, 24, and 48 hours during ropivacaine/fentanyl infusion than in
      patients receiving ropivacaine alone (12 h: 91% +/- 2% vs. 95% +/- 2%, p < 0.006;
      24 h: 93% +/- 1% vs. 96% +/- 2%, p = 0.003; 48 h: 92% +/- 1.8% vs. 96% +/- 1%, p
      = 0.004). CONCLUSIONS: A thoracic epidural infusion of 0.2% ropivacaine, with or
      without fentanyl, provided effective pain relief in most patients with a very low
      degree of motor blockade. Adding 2 microg/ml fentanyl to 0.2% ropivacaine reduced
      total consumption of local anesthetic solution and need for incremental doses,
      but did not provide clinically relevant advantages in quality of pain relief and
      incidence of motor block, leading to a significant decrease in peripheral SpO(2),
      lasting up to 48 hours after surgery.

PMID- 10960202
TI  - Patients' perception of sound levels in the surgical suite.
AB  - STUDY OBJECTIVES: To measure sound levels that our patients are exposed to in the
      surgical suite and their perception of these sound levels. DESIGN: Sound levels
      experienced by 100 patients undergoing general anesthesia for elective surgery
      during three phases: induction and maintenance of anesthesia in the operating
      room (OR), and recovery from anesthesia in the recovery room, were measured using
      a Type 4436 Noise Dose Meter. The equivalent continuous sound levels (Leq),
      maximum sound levels (Lmax), and the sources of sounds were noted. Patients were
      interviewed 24 hours after anesthesia about their perception of the sound levels
      they had experienced in the OR and recovery rooms. MEASUREMENTS AND MAIN RESULTS:
      The Leq during the induction, maintenance, and recovery phases were 70.3 +/- 16.8
      dB(A), 66.2 +/- 4.1 dB(A) and 71.8 +/- 6.1 dB(A), respectively. These sound
      levels are much higher than international recommendations for hospital acute care
      areas and exceed the thresholds to produce noise-induced cardiovascular and
      endocrine effects. Sound levels were significantly higher during the induction
      and recovery phases compared to the maintenance phase. Thirty-two patients found
      the induction phase noisy and 33 patients found the recovery phase noisy. The
      sound levels distressed 16 patients and 52 patients would have preferred a
      quieter environment. There was no difference in the sound levels experienced by
      those who expressed dissatisfaction with the sound levels and those who did not.
      Much of the noise, particularly staff conversations, unnecessary alarms, and
      preparation of equipment, could have been prevented by simple measures.
      CONCLUSION: Noise prevention in the OR and recovery room needs more attention and
      should be a routine part of patient care.

PMID- 10960203
TI  - Maintaining sevoflurane anesthesia during low-flow anesthesia using a single
      vaporizer setting change after overpressure induction.
AB  - STUDY OBJECTIVE: A sevoflurane vaporizer dial setting of 1.9% was previously
      found to maintain the end-expired sevoflurane concentration (Et(sevo)) at 1.3%
      during maintenance of anesthesia for procedures up to one hour with an O(2) FGF
      of 1 L/min. We examined whether applying these parameters could simplify low-flow
      sevoflurane anesthesia after overpressure induction using two slightly different
      techniques. DESIGN: Prospective clinical study. SETTING: Large teaching hospital.
      PATIENTS: Sixteen patients receiving general anesthesia for a variety of
      peripheral procedures. INTERVENTIONS: Anesthesia was induced with overpressure
      with sevoflurane (8%) in an 8 L. min(-1) O(2)/N(2)O mixture (30%/70%). After a
      laryngeal mask airway (LMA) was placed, fresh gas flow (FGF) was lowered to 1 L.
      min(-1) using O(2) and N(2)O (FiO(2) 30%) with patients breathing spontaneously.
      In group I patients (n = 8), the vaporizer dial was set at 1.9% at the same time
      the FGF was lowered. In group II patients (n = 8), the vaporizer was turned off
      until Et(sevo) had decreased to 1.3%, after which the dial was set at 1.9%. The
      course of Et(sevo) in the two groups was examined. MEASUREMENTS AND MAIN RESULTS:
      In group I, Et(sevo) after 3 min was 4.88 +/- 1. 12%. Et(sevo) decreased slowly
      after reduction of FGF to 1.83 +/- 0. 19%, 1.59 +/- 0.18%, and 1.52 +/- 0.19% at
      10, 20, and 30 min, respectively. In group II, Et(sevo) after 3 min was 4.34 +/-
      0.84%, and decreased more rapidly after reduction of FGF to 1 L. min(-1) than in
      group I. Et(sevo) was 1.40 +/- 0.09%, 1.40 +/- 0.11%, and 1. 38 +/- 0.13% at 10,
      20, and 30 min, respectively. CONCLUSIONS: After high-flow overpressure induction
      with sevoflurane, a single change in vaporizer setting (to 1.9%) and FGF (to 1 L.
      min(-1)) suffices for the Et(sevo) to approach the predicted Et(sevo) (1.3%)
      within 10-15 min; thereafter the Et(sevo) remains nearly constant. As expected,
      the predicted Et(sevo) is attained slightly faster when the vaporizer is
      temporarily turned off. Clinically applying previously derived pharmacokinetic
      parameters simplifies low-flow sevoflurane anesthesia after overpressure
      induction.

PMID- 10960204
TI  - Transesophageal echocardiographic assessment of pulmonary arterial and venous
      flow during high-frequency jet ventilation.
AB  - STUDY OBJECTIVE: To evaluate high-frequency jet ventilation (HFJV) effects on
      pulmonary arterial and venous flow compared to those of intermittent positive
      pressure ventilation (IPPV) by using pulsed Doppler transesophageal
      echocardiography. DESIGN: Prospective clinical study. SETTING: University
      affiliated hospital operating room. PATIENTS: 13 ASA physical status I and II
      patients undergoing lower abdominal or lower extremity surgery. INTERVENTIONS:
      PATIENTS had total IV anesthesia with propofol and fentanyl. After anesthesia
      induction, a transesophageal echocardiography probe was inserted into the
      esophagus. IPPV (TV, 8-10 mL/kg; respiratory rate, 10-12 cycles/min; I/E ratio,
      1:2; FIO(2), 1.0) and HFJV (driving pressure, 0.5-0.6 kgf/cm(2); frequency,3 Hz;
      I/E ratio, 1:1; FIO(2), 1.0) were performed under hemodynamically stable
      conditions. MEASUREMENTS: Pulmonary-arterial-flow velocity, pulmonary-venous-flow
      velocity, left ventricular short-axis view, and airway-pressure curve were
      recorded simultaneously. Parameters measured were: hemodynamic variables,
      arterial blood gases, inspiratory airway pressure; [from pulmonary-arterial-flow
      velocity] pre-ejection period (PEP), acceleration time (AT), right ventricular
      ejection time (RVET), and their ratios (PEP/AT, AT/RVET); [from pulmonary-venous
      flow velocity] time-velocity integral of the first systolic wave (S1), second
      systolic wave (S2), and diastolic wave (D), and systolic fraction (integral S1 +
      S2/S1+ S2 + D); [from M-mode] left-ventricular-end systolic volume, left
      ventricular-end diastolic volume (LVEDV), stroke volume, cardiac output, and
      ejection fraction, using Teichholz's method. MAIN RESULTS: Peak inspiratory
      airway pressure during HFJV was significantly lower than that during IPPV. HFJV
      significantly decreased PEP/AT, correlating positively with pulmonary arterial
      pressure, and significantly increased AT and AT/RVET, correlating negatively with
      pulmonary arterial pressure. Systolic fraction, correlating negatively with left
      atrial pressure, increased significantly during HFJV, as did LVEDV, stroke
      volume, cardiac output, and ejection fraction. CONCLUSIONS: Our results suggest
      that, in comparison to IPPV, HFJV significantly decreases pulmonary arterial
      pressure and left atrial pressure, resulting in significant increases in cardiac
      output and ejection fraction in healthy anesthetized adults.

PMID- 10960206
TI  - Poor prediction of blood transfusion requirements in adult liver transplantations
      from preoperative variables.
AB  - STUDY OBJECTIVE: To assess the ability of preoperative information to predict
      intraoperative blood transfusion requirements in adult orthotopic liver
      transplantation. DESIGN: Retrospective review. SETTING: Liver transplantation
      program in a referral center. PATIENTS: 583 sequential adult patients undergoing
      orthotopic liver transplantation. MEASUREMENTS: Preoperative variables with a
      previously demonstrated relationship to intraoperative transfusion were
      identified from the literature. These variables were then collected
      retrospectively from 583 consecutive liver transplantations. Relationships
      between these and intraoperative blood transfusion requirements were examined by
      both univariate analyses and multiple linear regression analysis. RESULTS:
      Univariate analysis revealed significant associations between blood transfused
      and the following preoperative variables: age, gender, diagnosis, presence of
      grade 3 or 4 encephalopathy, pseudocholinesterase, creatinine, bilirubin, mean
      pulmonary artery pressure, activated partial thromboplastin time, and platelet
      count. Multiple linear regression analysis with correction for diagnosis
      identified age, creatinine, bilirubin, and pseudocholinesterase as independent
      predictors; for the final model r(2) = 0.22. CONCLUSION: Preoperative variables
      are poor predictors of intraoperative transfusion requirements even when
      significant associations exist, identifying a small proportion of the variability
      observed. A predictive approach based on this method would be too inaccurate to
      be of clinical use. The majority of the variability in transfusion requirements
      during liver transplantation most likely results from intraoperative and donor
      organ factors.

PMID- 10960205
TI  - Differential effects of right versus left stellate ganglion block on left
      ventricular function in humans: an echocardiographic analysis.
AB  - STUDY OBJECTIVES: To evaluate the effects of unilateral stellate ganglion
      blockade on left ventricular function. DESIGN: Prospective cohort of patients
      with chronic regional pain syndrome type I and II of the upper extremity
      requiring therapeutic stellate ganglion blockade. SETTING: University-affiliated
      hospital. PATIENTS: Fifteen adult ASA physical status I and II patients with the
      diagnosis of chronic regional pain syndrome type I and II of the arm were
      studied. Right stellate ganglion block was performed in nine subjects and a left
      in six. INTERVENTIONS: Stellate ganglion block was performed with 10 mL of 1%
      plain Xylocaine. Transthoracic echocardiograms were performed immediately prior
      and 30 min following the block. MEASUREMENTS: Heart rate and blood pressure were
      monitored at regular intervals. Global systolic function was determined by
      calculating ejection fraction. Regional systolic motion was evaluated on the
      short axis and four-chamber views using the American Society of Echocardiography
      criteria. Diastolic function was assessed with pulsed-wave Doppler of the left
      ventricular outflow tract and the mitral valve. Data collected included
      isovolumic relaxation time and early and atrial velocity patterns. MAIN RESULTS:
      A successful stellate ganglion block was achieved in all patients. Blood pressure
      and heart rate were not significantly different during data collection. Patients
      who underwent a right stellate ganglion block showed no significant differences
      in systolic or diastolic function. Following a left stellate ganglion block,
      global and regional systolic function remained unchanged. Isovolumic relaxation
      time was increased but did not reach statistical significance (80 +/- 13 ms to 88
      +/- 9 ms; p = 0.09). Left ventricular end-diastolic (LVEDV) and end-systolic
      volumes (LVESV) were significantly increased (LVEDV from 73 +/- 9 mL to 100 +/- 9
      mL, p < 0.02; LVESV from 31 +/- 4 mL to 37 +/- 4 mL, p < 0.03). CONCLUSIONS: In
      patients without cardiovascular disease, unilateral denervation of the left
      ventricle after stellate ganglion block produces no clinical deleterious effects
      on left ventricular function.

PMID- 10960207
TI  - In vitro cross-reactivity of danaparoid sodium in patients with heparin-induced
      thrombocytopenia type II undergoing cardiovascular surgery.
AB  - STUDY OBJECTIVES: To assess the cross-reactivity of danaparoid sodium in patients
      undergoing cardiovascular surgery. DESIGN: Prospective investigation. SETTING: A
      major European heart center and university hospital. PATIENTS: 81 patients who
      underwent cardiovascular surgery during the period between January 1998 and April
      1999 and were diagnosed with heparin-induced thrombocytopenia (HIT) II.
      INTERVENTIONS: Testing was performed in patients who revealed a decrease in the
      platelet count >30% or a platelet count <100,000/microL during heparin therapy.
      Testing for HIT was performed by the use of the heparin-induced platelet
      aggregation assay. Patients were evaluated as positive if an agglutination
      occurred in two of four of the 0.2 IU/mL heparin chambers. Patients were judged
      to be cross-reactive with danaparoid sodium when an agglutination occurred in two
      of four chambers that contained 0.2 IU/mL Orgaran. MEASUREMENTS AND MAIN RESULTS:
      281 patients (5.4% of the patients who underwent surgery during the period of the
      investigation) were tested for HIT II. Of these, 81 (1.5% of the total) gave a
      positive heparin-induced platelet-aggregation assay and 23 (28%) revealed a cross
      reactivity with danaparoid sodium. CONCLUSION: Cross-reactivity with heparin
      induced platelet antibodies occurred in 28% of the patients who tested positive
      for heparin-platelet antibodies. In these patients, Orgaran would not have been a
      safe option. In patients with HIT II undergoing cardiac surgery, cross-reactivity
      with danaparoid sodium must be excluded before initiation of therapy with
      Orgaran, otherwise, or in cases of cross-reactivity, other options such as r
      hirudin are preferred.

PMID- 10960208
TI  - The American Society of Anesthesiologists' Physical Status: category V revisited.
AB  - STUDY OBJECTIVE: To determine the perioperative mortality and intraoperative
      morbidity according to operative procedure and postoperative period for American
      Society of Anesthesiologists' Physical Status (ASA-PS) V category patients.
      DESIGN: Retrospective chart review. SETTING: University-affiliated medical
      center. MEASUREMENTS AND MAIN RESULTS: The perioperative records of 111,051
      consecutive anesthetized patients, from 1990 to 1997 were retrospectively
      reviewed. Data were collected and analyzed to determine ASA-PS classification,
      perioperative mortality, intraoperative morbidity, mortality according to
      operative procedure, and mortality postoperatively for ASA-PS V patients. At the
      University of Florida, 0.37% of our patients were ASA-PS V. Most had anesthesia
      for abdominal (26.2%), cardiothoracic (27.9%), cranial (12.3%), or diagnostic
      procedures (11.6%). The overall mortality rate decreased in 1993-1995 and 1995
      1997, compared to 1990-1993, from 64.16 +/- 4.53 (+/-SD) to 46.7 +/- 9.5 and 56.8
      +/- 1.1, respectively. The mortality rate decreased in the immediate
      postoperative period from 15.7 +/- 5.1 to 4.6 +/- 1.5 and 4.1 +/- 2. 8
      intraoperatively, and from 42.5 +/- 1.8% to 22.1 +/- 5.1 and 26.8 +/- 1.8 within
      24 hours postoperatively. The mortality rate increased from 0 +/- 0 to 7.4 +/-
      3.9 and 15.5 +/- 4.9 (p < 0.05 for all), during the late postoperative period (>2
      weeks, during hospitalization). Intraoperative morbidity (untoward events) was
      significantly higher for ASA-PS V patients than for ASA-PS IV patients only in
      emergency cases (11.1 +/- 4.8% vs. 5.5 +/- 1.4%). CONCLUSIONS: The ASA-PS V
      classification is determined subjectively rather than objectively, and can be
      variable within its parameters, depending on the individual interpretation of ASA
      classification, patient population, case severity, surgical and anesthesia
      factors, and the year of the study. Even though immediate perioperative mortality
      decreased in our patient population, late postoperative mortality increased
      during the same time period, possibly demonstrating a shift in mortality time
      rather than an absolute decrease in overall mortality. Although the ASA-PS V
      category was never intended to be a predictor of outcome, it correlates with
      perioperative mortality as well as or even better than other classifications of
      mortality and morbidity. The decreased mortality in the ASA-PS V patient
      population may be related to different factors, which are beyond the scope of
      this study.

PMID- 10960209
TI  - Coronary artery plaque disruption as cause of acute myocardial infarction during
      cesarean section with spinal anesthesia.
AB  - A 31-year-old parturient delivered twins at 35 weeks' gestation by cesarean
      section with spinal anesthesia. Following anesthesia induction, hypotension and
      bradycardia occurred, and were immediately treated with theodrenaline plus
      cafedrin (Akrinor) and atropine. Blood pressure and heart rate increased to
      180/100 mmHg and 140 beats per minute, respectively. Several minutes later, the
      patient developed a myocardial infarction (MI) that she survived after intensive
      care treatment without sequelae. Although the coronary angiography showed normal
      coronary vessels, an intravascular ultrasound study demonstrated an atheroma in
      the left main coronary artery with ruptured fibrous cap. Laboratory screening for
      risk factors of coronary artery disease (CAD) showed hypercholesterinemia,
      increased factor VII activity, and hyperfibrogenemia. Angiographically normal
      coronary vessels are frequently found in pregnant patients who suffered MI. In
      these patients, coronary spasms have been discussed as the major mechanism of
      disease. Our case demonstrates that a significant CAD may be present despite
      angiographically normal findings. Plaque rupture was triggered by hypertension
      and led to MI as the first symptom of disease. On the basis of these findings, we
      believe that MI during pregnancy is more often caused by plaque rupture than may
      be expected, according to the current literature.

PMID- 10960211
TI  - Thinness: drives and results.

PMID- 10960210
TI  - Liver transplantation for hepatic arteriovenous malformation with high-output
      cardiac failure in hereditary hemorrhagic telangiectasia: hemodynamic study.
AB  - We describe a case of orthotopic liver transplantation used as a therapeutic
      method to correct high output cardiac failure related to a liver arteriovenous
      fistula due to hereditary hemorrhagic telangiectasia. Detailed hemodynamic
      changes as they occurred during liver transplantation are described.

PMID- 10960212
TI  - Urinary leukotriene (LT) E(4) in adolescents with dysmenorrhea: a pilot study.
AB  - In the present study we measured levels of urinary leukotriene (LT) E(4) as an
      index of LT production during the menstrual cycle in adolescents. Mean urinary
      LTE(4) levels in girls with dysmenorrhea was approximately threefold higher than
      normal laboratory values on Day 1 of the menstrual period and approximately
      twofold higher than normal laboratory values on Day 5 of the menstrual period.
      Compared with urinary LTE(4) levels in girls with eumenorrhea, urinary LTE(4)
      levels in girls with dysmenorrhea were higher on Day 1 [361 +/- 123 pg/mg
      creatinine vs. 122 +/- 37 pg/mg creatinine, p =.1; not significant (NS)] and on
      Day 5 (202 +/- 26 pg/mg creatinine vs. 117 +/- 26 pg/mg creatinine, p <.05) of
      the menstrual period, as well as on Day 10 (159 +/- 33 pg/mg creatinine vs. 88 +/
      21 pg/mg creatinine, p =.1; NS) of the menstrual cycle. Increased urinary
      excretion of leukotrienes, inflammatory mediators known to cause potent
      vasoconstriction and uterine contractions, in girls with dysmenorrhea in this
      pilot study, suggests that these mediators may be involved in generating
      dysmenorrhea symptoms in adolescents.

PMID- 10960213
TI  - Video intervention/prevention assessment: a patient-centered methodology for
      understanding the adolescent illness experience.
AB  - OBJECTIVE: To better understand the issues and needs of adolescents with chronic
      health conditions, the Video Intervention/Prevention Assessment (VIA) integrates
      video technology with qualitative research methods to obtain a patient-centered
      perspective on illness and health care. METHODS: Young people with chronic
      disease are interviewed for condition-specific verbal reports (CSVRs) of their
      medical and psychosocial histories. Standardized health-related quality of life
      (HRQL) instruments are administered. Trained to use video camcorders,
      participants record visual narratives of their illness experiences. They document
      their daily lives, interview families and friends, and record personal monologues
      regarding their observations, behaviors, understandings, and beliefs about their
      disease. On completion of the visual narratives, HRQL is again evaluated. Verbal,
      scaled, and visual data are analyzed from three perspectives: medical,
      psychosocial, and anthropological. Data from the CSVRs, HRQLs, and visual
      narratives are triangulated to validate and enrich findings. RESULTS:
      Investigating the illness experience from the adolescent patient's perspective,
      the VIA method was pilot-tested with children and adolescents with asthma. As a
      research tool, VIA found environmental risk factors, medication adherence
      problems, and outcome-affecting illness beliefs and psychological states that
      were not identified by standard clinical tools. As an intervention, VIA showed
      that it may be an effective tool for health-related environmental surveys.
      Participants' condition-specific quality of life showed measurable improvement
      after the self-examination process of VIA. As communication, VIA made apparently
      counterproductive patient behaviors understandable by showing them in context
      with the adolescent's experience of illness and health care. VIA can enhance
      medical history-taking and management strategies, improve adolescents' self
      management skills, and educate clinicians, families, and students of the health
      care professions about the realities of the adolescent living with a chronic
      health condition.

PMID- 10960214
TI  - Family planning services at school-based health centers: findings from a national
      survey.
AB  - Although nearly 1000 school-based health centers (SBHCs) operate in the United
      States, little is known about SBHCs' sexual and reproductive health services.
      This study investigated reproductive and sexual health services delivery in
      SBHCs, specifically the types of services available in SBHCs. A 16-page, self
      administered questionnaire asked center staff to identify the reproductive health
      services provided on site as well as which services were restricted and by whom.
      The results suggest that whereas most SBHCs provided at least one reproductive
      health service, most centers were restricted from providing contraceptive
      services, usually by school district policy.

PMID- 10960215
TI  - Gallagher lecture. The family at adolescence: transition and transformation.

PMID- 10960216
TI  - Unprotected sex as a function of alcohol and marijuana use among adolescent
      detainees.
AB  - PURPOSE: To examine the relationship between the use of two substances (alcohol
      and marijuana) and the occurrence of unprotected sexual intercourse among
      adolescent detainees. METHODS: Participants were asked about their use of
      alcohol, marijuana, and condoms. In addition to comparing levels of alcohol and
      marijuana use, the study examined relationships among the following variables:
      (a) the number of days that each substance was used and the number of unprotected
      episodes of sexual intercourse in the 30 days preceding admission to a youth
      detention center; (b) the number of times that each substance was used before or
      during sexual intercourse and the number of unprotected episodes in the same time
      period; (c) the use of each substance and unprotected intercourse at the last
      sexual episode; and (d) intentions to use each substance in the context of sex
      and to have unprotected intercourse in the future. Relationships among these
      variables were assessed in four regression models, each of which included
      participants' demographic characteristics, AIDS knowledge, attitudes toward
      condoms, and future orientation as covariates. RESULTS: Results of all four
      regression models indicated that marijuana use was associated with unprotected
      sexual intercourse. Adolescents who used more marijuana in general as well as
      specifically in sexual episodes in the 30 days preceding detention reported
      higher levels of unprotected sex. In addition, marijuana use in the last episode
      was related to the occurrence of unprotected sex during that episode. Moreover,
      intentions to use marijuana in future sexual episodes was associated with
      intentions to have unprotected intercourse in the future. CONCLUSIONS: Future
      studies should use more rigorous research designs to clarify the nature of the
      relationship between marijuana use and risky sex.

PMID- 10960217
TI  - Use of reproductive health services among young men, 1995.
AB  - PURPOSE: To analyze the extent to which teenage males receive preventive
      reproductive health services and identify demographic and health factors
      associated with their receipt. METHODS: Bivariate and multivariate analyses of
      nationally representative data from the 1995 National Survey of Adolescent Males
      were conducted using logistic regression to determine which factors predicted
      whether teenagers had a physical examination and whether they discussed
      reproductive health topics with a medical professional, had a human
      immunodeficiency virus (HIV) test, or had a sexually transmitted disease (STD)
      test. RESULTS: Although 71% of males aged 15-19 years received a physical
      examination in the past year, only 39% of them received any of the three
      reproductive health services. Less than one-third of all young men discussed
      reproductive health with their doctor or nurse. Among sexually experienced males,
      one-sixth had an STD test and one-quarter an HIV test. In multivariate analysis,
      males who had a physical examination were more likely to have an STD or HIV test,
      but were no more likely to discuss reproductive health topics. Minority and low
      income youth were more likely to receive these reproductive health services, as
      were young men with multiple sex partners and those with health problems.
      CONCLUSIONS: In general, the proportion of teenage men receiving reproductive
      health services is low, although levels are higher among minority youth and
      certain groups at risk. To reduce rates of teen pregnancy and STDs, physicians
      and nurses need to incorporate reproductive health care into routine health
      services for teenage males, as well as females.

PMID- 10960218
TI  - Factors associated with assault-related firearm injuries in male adolescents.
AB  - PURPOSE: To identify factors associated with an increased prevalence of assault
      related firearm injuries in male adolescents. METHODS: This study is a
      retrospective comparison of two samples of adolescent males from the same
      geographic localities regarding their involvement in the juvenile justice system
      (court involvement) and injury status (current or prior firearm injury at the
      time of the study). The subjects included adolescent male patients admitted to an
      urban, Level I trauma center for assault-related firearm injuries (court-involved
      and noncourt- involved, n = 65); and incarcerated juvenile offenders (prior
      firearm injury and no known firearm injury, n = 267). RESULTS: Two-thirds of the
      male assault-related pediatric firearm injury victims treated over a two-year
      period were involved in the juvenile justice system (court involved). Court
      involved adolescents were almost 22 times more likely to have sustained an
      assault-related firearm injury, when compared to noncourt-involved patients with
      firearm injuries. Additional analysis documented recent substance use and/or
      involvement in criminal offenses in 82% of the victims. For most of the juvenile
      offenders (88%), court involvement preceded their injuries. Analysis of the
      injury patterns revealed an increased prevalence of truncal injuries (injuries to
      thorax or abdomen) in the court-involved victims, when compared to their noncourt
      involved peers (40% and 14% for the court-involved and noncourt-involved samples,
      respectively; p <.05). Incarceration was associated with a 17-fold increase in
      the firearm injury prevalence over the court-involved, but not incarcerated,
      sample. CONCLUSIONS: These results suggest that involvement in substance use
      and/or the criminal justice system is associated with an increased risk of
      firearm injuries in male adolescents, and that an increased level of involvement
      in the juvenile justice system is associated with a concomitant increase in
      firearm injuries.

PMID- 10960219
TI  - Psychosocial and environmental correlates of violence perpetration among African
      American urban youth.
AB  - PURPOSE: To ascertain the proportion of youths involved in acts of violence; to
      examine individual, social, and environmental factors associated with
      perpetration; and to determine the relationship among victimization, witnessing,
      and perpetration of violence. METHODS: A cross-sectional survey was completed by
      349 volunteer males and females, aged 9-15 years, 96% of whom were African
      American. The youths were recruited from recreation centers associated with 10
      public-housing communities in an eastern city. Survey instruments included the
      Child Health and Illness Profile, Survey of Children's Exposure to Community
      Violence, and other standardized questionnaires. Statistical analyses included
      Chi-square, correlation, regression, and test for linear trends. RESULTS: Half of
      the youths self-reported at least one act of violence perpetration, with similar
      distributions among males and females. One-third of the youths reported both
      personal victimization and the witnessing of violent events. Victim and witness
      status were moderately correlated. Individual risk behaviors and victimization
      made significant contributions to perpetration status. Further analysis
      demonstrated a linear relationship between acts of perpetration and number of
      victimization events. CONCLUSIONS: Participation in problem behaviors may place
      youths in circumstances in which they may be victim, witness, or aggressor. The
      chronic and high levels of community violence to which many youths are exposed
      are likely to contribute to an individual's participation in acts of violence.

PMID- 10960220
TI  - Prevalence of coronary heart disease risk factors in Costa Rican adolescents.
AB  - PURPOSE: To determine the prevalence of coronary heart disease (CHD) risk factors
      among Costa Rican adolescents. METHODS: The prevalence of high blood pressure,
      obesity, total cholesterol, high-density lipoprotein (HDL) cholesterol, low
      density lipoprotein (LDL) cholesterol, sedentarism, family history of premature
      CHD, saturated fat intake, diabetes mellitus, and cigarette smoking was
      determined in 328 adolescents, ages 12-18 years (167 males, 161 females),
      randomly selected from San Jose's urban and rural high schools. RESULTS: Over 70%
      of the adolescents studied presented one risk factor for CHD. While the
      prevalence of family history of premature CHD, sedentarism, and cigarette smoking
      was significantly higher in urban adolescents, low HDL cholesterol and high blood
      pressure were significantly higher in rural adolescents. Girls demonstrated a
      significantly higher prevalence of sedentarism and LDL cholesterol >2.9 mmol/L
      than boys. Elevated saturated fat intake (>10% total energy) was found in 37% of
      the adolescents. CONCLUSIONS: The prevalence of CHD risk factors among Costa
      Rican adolescents is high; particularly of saturated fat intake, sedentarism and
      low HDL-C levels. Primary prevention programs are urgently needed, especially
      among female adolescents and in the urban areas, to reduce the increased
      prevalence of CHD mortality among Costa Rican adults.

PMID- 10960221
TI  - Fighting among Jerusalem adolescents: personal and school-related factors.
AB  - PURPOSE: To study the prevalence of physical fighting among youth and its
      association with personal and school-related factors. METHODS: Pupils in the 8th
      and 10th grades (n = 1182, ages 13-16 years) in 11 Jerusalem secular and
      religious schools anonymously completed the World Health Organization
      questionnaire from the Health Behavior in School Children study. The unit of
      analysis was defined as the number of times the student was involved in physical
      fighting during the past year. The independent variables studied were
      sociodemographic characteristics, personal, and school-related factors including
      teachers, peers, and family. RESULTS: Fighting at least once was reported by 76%
      of boys and 26% of girls; 6% of boys who were involved in fights at least once
      and 16% more than once required medical treatment. For boys, bullying others,
      poor health and mental health score, and perception of teachers that the pupil
      was a below-average student significantly increased the odds ratio (OR) for
      fighting more than once in the past year. Among girls, poor mental health, poor
      parental support on school matters, bullying, and being bullied by others
      increased the OR for fighting. CONCLUSIONS: Fighting is a highly prevalent
      behavior among adolescents irrespective of their socioeconomic background.
      Determinants differ by gender, and intervention programs should focus on the
      gender-specific determinants.

PMID- 10960222
TI  - Re: Surgery or not for fully accommodative esotropia: solomonic solutions to the
      controversy quarterly.

PMID- 10960223
TI  - Strabismus surgery dosage and timing; outcomes: minitropias and microtropias;
      stereotests for screening.

PMID- 10960224
TI  - Esotropia surgery in children: long term outcome regarding changes in binocular
      alignment; a study of 956 cases.
AB  - PURPOSE: To study the correlation between the outcome at 1 month (when the
      postoperative eye position is at the earliest stabilized), and 4 years after
      surgery. METHOD: Retrospective review of medical records. CASES: The authors
      reviewed 956 patients under 15 years of age who underwent unilateral or bilateral
      recession of the medial rectus muscle during a 22 year period representing the
      entire practice period of the senior author since the department was founded in
      1977. The series comprised 521 cases of congenital/infantile esotropia (manifest
      before 6 months of age with no accommodative component) and 435 cases of acquired
      esotropia (manifest after 6 months of age with no accommodative component or with
      an accommodative component but excluding those with a high AC/A ratio). A
      consistent surgical plan was employed throughout this period for each condition.
      RESULTS: Both types of esotropia showed a slight tendency to become exotropic
      during the 4 years after surgery. There was no difference in general success with
      regard to the reconstructive restoration of normal appearance or improvement of
      appearance between 1 month and 4 years after surgery. Patients with normal
      retinal correspondence or simultaneous perception achieved better binocular
      alignments at the 4 year followup than those who did not have such sensory
      binocular cooperation. CONCLUSIONS: In infantile and acquired esotropia, it is
      essential that orthotropia or minimal esotropia be present at 1 month of surgery
      in order to obtain a binocular alignment within +/- 4 PD of orthotropia 4 years
      after surgery. It is strongly recommended to avoid overcorrection (consecutive
      exotropia) at 1 month after surgery for both congenital/infantile and acquired
      esotropia.

PMID- 10960225
TI  - Near stereoacuity: development in preschool children; normative values and
      screening for binocular vision abnormalities; a study of 115 children.
AB  - PURPOSE: Because of controversial results in previous reports, we wished to
      further evaluate stereoacuity development in children with normal binocular
      vision, and to investigate the reliability of stereoscopic tests for screening
      for abnormal binocular vision and amblyopia. MATERIALS AND METHODS: In a
      prospective study, 115 children, age 3 to 6 1/2 years, were first tested on the
      TNO and Titmus Stereotests, after which they received a more complete eye
      examination to determine the presence of ocular and vision abnormalities. Only
      specific quantitative stereotest results were tabulated for the development
      study. RESULTS: Binocular vision anomalies were detected by stereotesting in 3 of
      the 115 children. Testability was better on the TNO than the Titmus Stereotest.
      Using only the quantitative stereotest results, when segregated by age groups,
      there was a "statistically significant" change (improvement with age) on the TNO
      Test (p=.0001)(x2); whereas there was no such improvement found on the Titmus
      Stereotest Circles, p=.045, 0.72. CONCLUSIONS: The TNO Test is reliable for
      screening for binocular vision anomalies and amblyopia. Also, normal stereopsis
      and stereoacuity acuity improves "significantly" between age 4 and 5 1/2 years,
      and reaches adult-like level at 5 1/2 years on this test.

PMID- 10960226
TI  - BVAT distance vs. near stereopsis screening of strabismus, strabismic amblyopia
      and refractive amblyopia; a prospective study of 68 patients.
AB  - PURPOSE: Although there have been studies in the past of the difference between
      distance and near stereopsis in intermittent exotropia, no such comparisons have
      been studied and/or reported for other forms of strabismus, nor for strabismic
      functional amblyopia, or for refractive functional amblyopia. METHODS: The study
      was prospective: Sixty-eight consecutive patients, ages 6-76 years, with either
      childhood onset strabismus and no amblyopia, childhood onset strabismus and
      amblyopia, or refractive amblyopia and no strabismus, had their stereopsis
      measured. Distance stereopsis was determined on the Mentor BVAT with Random Dot E
      Test (global stereopsis) and the Circle Test (contour stereopsis). Near
      stereopsis was determined with the Circle Test of the Randot Stereotest. The data
      were tabulated and analyzed statistically. RESULTS: Of the 26 strabismus/no
      amblyopia cases, 14 (54%) appreciated distance stereopsis. Of these, 12/14 were
      intermittent, and other 2 who were constant had deviations of 8 PD or less. Only
      4 of the 14 appreciated global stereopsis at distance (mean = 90 sec. of arc),
      but all 14 appreciated contour stereopsis at distance (mean = 125 sec. of arc).
      Of all 26, 21 (81%) had near stereopsis (mean = 137 sec. of arc). For the 21
      strabismic amblyopes, only one appreciated global stereopsis at distance (120 sec
      of arc), and 2 (10%) contour stereopsis at distance (mean = 210 sec. of arc).
      These two and 4 others (total 29%) had near stereopsis (mean = 162 sec. of arc).
      For the 21 refractive amblyopes, 3 appreciated global stereopsis at distance
      (mean = 220 sec. of arc), 11 in all, (52%) contour stereopsis at distance (mean =
      121 sec. of arc) and 20 (95%) had near stereopsis (mean = 78 sec. of arc). The
      percentages of patients in all categories capable of appreciating distance
      stereopsis were "statistically significantly" (P<.05) or clinically/medically
      significantly different from (less than) the percentages having near stereopsis.
      CONCLUSIONS: distance stereopsis is more likely to be reduced or absent than near
      stereopsis in strabismus, strabismic amblyopia and refractive amblyopia and thus
      appears to be more sensitive to, and better screening for, binocular vision
      disorders and a stronger and better outcome standard for treatment of binocular
      vision disorders than near stereopsis.

PMID- 10960227
TI  - Abnormal head posture: an ophthalmological approach.
AB  - BACKGROUND: An abnormal head posture (AHP) is an important clinical sign; it may
      be due to non-ocular or ocular causes. The literature on the subject is disperse,
      however. OBJECTIVE: To present a comprehensive discussion on the subject.
      CLINICAL CONDITIONS: AHP due to an ocular cause can be observed in conditions
      both not related or related to the extraocular motility. In the latter group,
      comitant deviations, incomitant deviations, supranuclear palsies, A and V
      pattern, nystagmus, and central nervous system disorders are included. Facial
      asymmetry can be a feature of a long-standing congenital or acquired AHP.

PMID- 10960228
TI  - A case of restrictive strabismus secondary to orbital Wegener's granulomatosis.

PMID- 10960229
TI  - Steroidophobia II: an unsubstantiated paper/opinion proposing frequent
      measurement of intraocular pressure after strabismus surgery managed
      postoperatively with topical steroids. Misplaced or excessive concern about IOP
      after strabismus surgery.

PMID- 10960230
TI  - No rebleeds in 250 cases of traumatic hyphema with the Yasuna "No Touch"
      protocol.

PMID- 10960231
TI  - Traumatic hyphema management: followup: where has the rebleed morbidity gone?
      Preventing school myopia with atropine and bifocals.

PMID- 10960232
TI  - Atropine and photochromic bifocals for 800 cases of school myopia.

PMID- 10960234
TI  - The ultimate in binocular vision; lefties are disabled by Definition? die,
      Darnit!; cadillacs and cops

PMID- 10960233
TI  - Management of progressive school myopia with topical atropine eyedrops and
      photochromic bifocal spectacles.
AB  - PURPOSE: To report our results of medical management of myopia, and add these to
      the prior literature supporting this practice. METHOD: Retrospective review of
      the medical records of 35 patient-subjects offered this treatment with adequate
      followup over a five year period. Treatment consisted of prescription of
      photochromic gray extra lenses incorporating full myopic correction with a +3.00
      bifocal addition, and atropine 1% ophthalmic drops, one in each eye, each night
      at bedtime. Compliance was monitored based upon mydriasis and cycloplegia.
      RESULTS: The mean change in refractive error per year was +0.07 diopters for the
      always compliant group, that is, a decrease in the amount of myopia; -0.18
      diopters per year for the sometimes compliant group; and -0.17 diopters for the
      never compliant group, an increase in the degree of myopia. Statistical
      comparison of our always compliant group with each of the other two groups using
      the t-test, yielded a P value of P<.10 in each case, considered to be
      "medically/clinically significant". Comparison of the mean annual change in
      refractive error of our always compliant group (+0.07 D/yr) with the mean annual
      change in re-fractive error in the general population aged 8-15 years (-0.24
      D/yr) shows an absolute difference of 0.31 D/yr. This difference is
      "statistically significant" (t-test) with a P <.02. CONCLUSION: Atropine and
      bifocals are an appropriate, effective, and safe management for progressive
      school myopia; and probably also for pathological myopia.

PMID- 10960237
TI  - Special section:travel medicine.

PMID- 10960236
TI  - Tennet: Theoretical and Experimental Neuropsychology 10th annual meeting.
      Montreal, Quebec, Canada. June 17-19, 1999. Proceedings.

PMID- 10960238
TI  - [Self-measurement of arterial pressure: a critical review].

PMID- 10960239
TI  - Cytomegalovirus infection following transplantation of autologous CD34-selected
      progenitor cells.

PMID- 10960240
TI  - Cyclosporine (CSP)or CSP plus methylprednisolone for graft-versus-host disease
      prophylaxis in patients with high-risk lymphohemopoietic malignancies: long-term
      follow-up of a randomized trial.

PMID- 10960241
TI  - The limitations of site-directed mutagenesis in the localization of Rh D
      epitopes.

PMID- 10960242
TI  - A potential role for leukemia inhibitory factor in the increased clonogenicity of
      human fetal progenitor cells.

PMID- 10960243
TI  - Evidence-based corneotherapy.

PMID- 10960245
TI  - Regarding the November 1998 Dermatologic Surgery issue.

PMID- 10960244
TI  - Regarding the use of compression stockings after sclerotherapy.

PMID- 10960246
TI  - Regarding the Castroviejo razor blade breaker and holder.

PMID- 10960247
TI  - Laser resurfacing and oral and maxillofacial surgeons.

PMID- 10960249
TI  - Prospective audit following the introduction of short course preoperative
      radiotherapy for rectal cancer.

PMID- 10960248
TI  - Comments of the use of post-sclerotherapy compression.

PMID- 10960250
TI  - Prospective audit following the introduction of short course preoperative
      radiotherapy for rectal cancer.

PMID- 10960251
TI  - Internet connections.

PMID- 10960252
TI  - Animal reproduction: research and practice II. Proceedings of the 14th
      International Congress on Animal Reproduction. Stockholm, Sweden, 2-6 July 2000.

PMID- 10960253
TI  - [Health surveillance in occupational medicine today. Bergamo, Italy, 19 March
      1999].

PMID- 10960254
TI  - Effects of trichloroethylene (TCE) on an in vitro chick atrioventricular canal
      culture.

PMID- 10960255
TI  - Stroke vignette. Duplex ultrasound diagnosis of carotid/vertebral dissection
      without hemodynamically relevant stenosis.

PMID- 10960256
TI  - [Nuclear Medicine: the future].

PMID- 10960257
TI  - Social medicine at the turn of the century and beyond: a symposium to honor the
      life and work of Martin Cherkasky, MD. New York, USA, December 1, 1998.
      Proceedings.

PMID- 10960259
TI  - Appeals Court says Food and Drug Administration can regulate Cholestin.

PMID- 10960258
TI  - Proceedings of the Twenty-third Arnold O. Beckman Conference in Clinical
      Chemistry.

PMID- 10960260
TI  - Making the "bench" hospitable to minority scientists.

PMID- 10960262
TI  - Evidence-based art of the clinical examination.

PMID- 10960261
TI  - Nucleic acids for recognition and catalysis: landmarks, limitations, and looking
      to the future.
AB  - Combinatorial selection of nucleic acids has led to the discovery of novel
      ligands and catalysts that have implications for both chemistry and medicine. In
      the context of combinatorial chemistry, degenerate syntheses of nucleic acid
      libraries readily generate as many as 10(15) different molecules in which a small
      percentage exhibit interesting binding and/or catalytic properties. The primary
      advantage of nucleic acids is that library coding is an intrinsic property;
      sequential composition directly determines the activity. At low temperatures, the
      sequential composition of single stranded nucleic acids governs folding into
      irregular tertiary structures resulting in interesting activities. At higher
      temperatures, the same structures are unfolded and decoded by polymerases to
      reveal sequential information. The use of PCR (polymerase chain reaction) permits
      amplification and thus enrichment of the selected activity which is then
      regenerated chemi-enzymatically. Iterative selection and amplification result in
      one of the highest throughput screens conceivable whereby each molecule encodes
      its own activity permitting the ultimate in parallel sampling. Finally, sequence
      information, and by extension the chemical composition, is obtained by simple
      sequencing techniques obviating the need for mass spectrometric deconvolution,
      parallel tagging, and/or large volumes needed for viral and cell culture. This
      review begins with an introduction of general concepts and considerations. The
      potential for nucleic acids to generate tight-binding ligands is of interest to
      structural biologists and medicinal chemists. The therapeutic implications to
      medicine are also touched upon. Since combinatorially selected nucleic acids and
      antibodies share many conceptual similarities, their respective advantages and
      limitations are compared. Theoretical and practical limitations for catalyst
      discovery are discussed along with the use of other chemical and physical
      approaches to address some current catalytic shortcomings. Finally some future
      directions are suggested.

PMID- 10960263
TI  - Sao Paulo Medical Journal/Revista Paulista de Medicina on the Scientific
      Electronic Library Online (SciELO)

PMID- 10960264
TI  - The relationship of social phobia to avoidant personality disorder: a proposal to
      reclassify avoidant personality disorder based on clinical empirical findings.

PMID- 10960265
TI  - Monthly birth rates in residual and paranoid schizophrenic patients.

PMID- 10960266
TI  - Infectious web.

PMID- 10960267
TI  - Re: The PEP-CHF study.

PMID- 10960268
TI  - The Heart Failure Journal Club: a review of publications on heart failure in
      Heart.

PMID- 10960269
TI  - Radiology is digitally headed.

PMID- 10960271
TI  - Assessment of the health risk of dioxins: re-evaluation of the tolerable daily
      intake (TDI). Geneva, Switzerland, 25-29 May 1998.

PMID- 10960270
TI  - Quiz case: acute pituitary apoplexy.

PMID- 10960272
TI  - Image of the month. A wind sock web deformity of the proximal duodenum.

PMID- 10960273
TI  - Thalidomide for Crohn's disease.

PMID- 10960274
TI  - Mesalamine and relapse prevention in Crohn's disease.

PMID- 10960275
TI  - Late onset and high incidence of colon cancer of the mutator phenotype with
      hypermethylated hMLH1 gene in women.

PMID- 10960276
TI  - Influence of vitamin D receptor gene polymorphism on bone mineral density in
      primary biliary cirrhosis.

PMID- 10960278
TI  - No fixed nucleotide difference between Africans and Non-Africans at the pyruvate
      dehydrogenase E1 alpha-subunit locus.

PMID- 10960277
TI  - COX-2 in murine intestinal tumors.

PMID- 10960280
TI  - Is there any relationship between IEL and lymphoid follicles in the gastric
      mucosa?

PMID- 10960279
TI  - Acid secretion in H pylori associated enlarged fold gastritis.

PMID- 10960281
TI  - hMLH1 and hMSH2 immunostaining in colorectal cancer.

PMID- 10960282
TI  - Silymarin: What is in the name...? An appeal for a change of editorial policy.

PMID- 10960284
TI  - Intravascular tumour in intraoral pleomorphic adenomas.

PMID- 10960283
TI  - Antibody response to hepatitis B virus vaccination in individuals with hepatitis
      C virus infection.

PMID- 10960285
TI  - Proceedings of a symposium on the neurobiology of the basal ganglia. Glasgow,
      United Kingdom, July 1999.
AB  - The basal ganglia occupy a commanding place in neuroscience research, in clinical
      neurology and in biomedical education. The paucity of our understanding of the
      role of the basal ganglia in normal everyday life combined with our more
      extensive knowledge of their deficiencies in a variety of clinical syndromes is a
      potent spur to continuing investigation. That some of these neurodegenerative
      syndromes-such as Parkinson's disease-are already common only heightens the need
      for insight in the face of a population with increasing expectations of
      longevity. About a decade ago an explosion of information on the connectivity and
      immunocytochemistry of forebrain structures gave rise to concepts which have
      shaped the fabric of basal ganglia theory-'patch and matrix', 'disinhibition',
      'parallel circuits'. Some of these ideas seemed to facilitate an understanding of
      the basal ganglia, others to render them more complex and impenetrable. Perhaps
      unsurprisingly, the work of the last decade has tended towards consolidation and
      refinement. However, several new developments are receiving attention, many of
      them related to disorders of the basal ganglia. The realisation that some forms
      of Parkinson's disease have a genetic determinant is gaining strength. The
      molecular biology of the dopaminergic synapse on the one hand and of the
      production of insoluble proteins on the other will clearly influence future
      research into therapeutic options and neuroprotection. The importance of
      apoptosis, neural plasticity and free radical formation remains unresolved but
      these are potential areas of promise. Meanwhile, scanning techniques for brain
      imaging are allowing real time investigation of the working striatum in normal
      and disordered humans and animals.We believe that the time is opportune for a
      broad review of current thinking on the basal ganglia in health and disease. The
      following articles are based on presentations given at a Symposium on the
      Neurobiology of the Basal Ganglia held at Glasgow University in July 1999 as part
      of the Summer Meeting of the Anatomical Society of Great Britain and Ireland. The
      invited speakers were chosen to be wide ranging and contributions encompassed
      evolution, circuitry and receptors of the basal ganglia, striatal remodelling
      after dopamine loss, striatal functioning in humans with Huntington's disease and
      in primate models after midbrain fetal transplants, and the genetics of basal
      ganglia disorders. Short presentations and posters of current results
      supplemented the main presentations and some are also included amongst these
      reviews.

PMID- 10960287
TI  - Emil Theodore Kocher (1841-1917).

PMID- 10960286
TI  - "It will not happen: not soon, not ever".

PMID- 10960288
TI  - Phantom limb sensations after complete thoracic transverse myelitis.

PMID- 10960289
TI  - Vestibular evoked myogenic potentials in multiple sclerosis.

PMID- 10960290
TI  - Sensory ataxia as the initial clinical symptom in X-linked recessive bulbospinal
      neuronopathy.

PMID- 10960292
TI  - Acute psychosis and EEG normalisation after vagus nerve stimulation.

PMID- 10960291
TI  - Neuroleptic malignant syndrome without fever: a report of three cases.

PMID- 10960293
TI  - A randomised double blind trial versus placebo does not confirm the benefit of
      alpha-interferon in polyneuropathy associated with monoclonal IgM.

PMID- 10960294
TI  - Reversible posterior leukencephalopathy syndrome induced by granulocyte
      stimulating factor filgrastim.

PMID- 10960295
TI  - Acute adverse reaction to fentanyl in a 55 year old man.

PMID- 10960296
TI  - Relapsing alternating ptosis in two siblings.

PMID- 10960298
TI  - Neurology at the frontier.

PMID- 10960297
TI  - Snapshot view of emergency neurolosurgical head injury care.

PMID- 10960299
TI  - Tardive Parkinsonism, orofacial dyskinesia and akathisia following brief exposure
      to lithium carbonate.

PMID- 10960301
TI  - Universal access to health.

PMID- 10960300
TI  - Doctor's and patients' facial expressions and suicide reattempt risk assessment.

PMID- 10960302
TI  - Laparascopically assisted vaginal resection of rectovaginal endometriosis.
AB  - BACKGROUND: We wanted to establish a technique of laparoscopically assisted
      radical vaginal surgery for deep endometriosis of the rectovaginal septum with
      extensive rectal involvement. TECHNIQUE: The procedure is started by vaginally
      excising the involved area which is left on the rectum, followed by bilateral
      dissection of the pararectal and retrorectal spaces. Para- and retrosigmoido
      rectal spaces are developed laparoscopically along the coccygeosacral bone and
      medially to the pelvic splanchnic nerves toward the para- and retrorectal
      openings that were made transvaginally. Rectal transection is done with a
      laparoscopic stapling device caudal to the endometriotic lesion. Using a
      suprapubic minilaparotomy, the bowel is transected cranial to the lesion and
      reintroduced into the abdomen, and a transanal circular stapler anastomosis is
      done. EXPERIENCE: Thirty-four women had this procedure. The mean distance of the
      anastomosis was 4 cm above the anus. None required ileostomy or colostomy and no
      major complications were noted. CONCLUSION: The combination of laparoscopic and
      vaginal approaches is useful for removing extensive endometriotic infiltration of
      the rectosigmoid; bladder and rectal function and fertility can be preserved.

PMID- 10960303
TI  - Prediction of birth weight by ultrasound in the third trimester.

PMID- 10960304
TI  - [Members of the Sociedade Brasileira de Medicina Tropical].

PMID- 10960305
TI  - [Re: "Comparative experimental study of 3 systems of osteosynthesis for fractures
      of the proximal humerus." P. Gicquel, F. Bonnomet, Ph. Boutemy, B. Schlemmer, J.
      F. Kempf. Rev. Chir. Ortho. 1999, 85, 811-820].

PMID- 10960306
TI  - [Infection with hepatitis C virus. Introduction].

PMID- 10960307
TI  - Emerging diseases. New arenavirus blamed for recent deaths in California.
AB  - Researchers say a new virus that appears to cause hemorrhagic fever is endemic-
      but at very low levels--in the western United States. Last week, the California
      Department of Health Services announced that a recently discovered virus carried
      by wood rats and pack rats killed a 14-year-old girl in April; moreover, the
      department says, there's strong evidence that the virus has caused at least two
      other deaths within the last 14 months. Experts say there is no cause for alarm,
      however, as they believe it to be a rare event.

PMID- 10960308
TI  - Agricultural biotechnology. Monsanto donates its share of golden rice.
AB  - Monsanto Co. has agreed to provide royalty-free licenses to speed up work on a
      genetically modified rice that could alleviate vitamin A deficiency around the
      world. Researchers welcomed last week's announcement, but warn that a thicket of
      intellectual property claims surrounds the technology and that significant legal
      hurdles remain before the rice can become widely available to farmers in
      developing countries.

PMID- 10960309
TI  - Public health. Gates Foundation on big funding spree.
AB  - The Bill and Melinda Gates Foundation dished up $200 million in grants for
      scientists in various fields late last month, including research into malaria and
      tuberculosis. The foundation kicked off its spending spree in mid-July at the
      XIII International AIDS Conference in Durban, South Africa, by announcing several
      AIDS/HIV-related grants totaling $90 million.

PMID- 10960310
TI  - Neurobiology. Long-sought protein packages glutamate.
AB  - Glutamate, one of two neurotransmitters that send the basic "stop" and "go"
      signals that most other neurotransmitters merely modulate, is called into action
      wherever rapid-fire excitatory signals are needed--say, for vision or learning.
      For decades, researchers have been looking for the protein that packages
      glutamate for express delivery to other neurons. On page 957, researchers report
      that they've found this elusive transporter, dubbed VGLUT1.

PMID- 10960311
TI  - Emerging diseases. Hunt for mad cow in sheep reassuring.
AB  - Experts on brain-riddling spongiform diseases have grown steadily more uneasy
      over signs that so-called mad cow disease or bovine spongiform encephalopathy
      (BSE), which is linked to a lethal human illness, may be lurking in sheep. A
      study in the 10 August issue of Nature now offers evidence that BSE is not
      rampant in sheep after all, although scientists are far from ready to let their
      guard down.

PMID- 10960312
TI  - New tools. A new breed of high-tech detectives.
AB  - Forensic scientists are equipping police investigators with powerful tools for
      collecting and analyzing evidence. But as detection techniques become
      increasingly sensitive, the problem of sifting the wheat from the chaff at a
      crime scene mushrooms, guaranteeing a role for the human investigator despite all
      the gadgetry. Moreover, some developments are also raising civil liberties
      concerns.

PMID- 10960313
TI  - Body chemistry. Where dead men really do tell tales.
AB  - Here at the "Body Farm," a research plot where human corpses are studied as they
      decompose, the corpses are teaching scientists much about how to reconstruct the
      manner and circumstances of unexplained deaths. In fact, new techniques developed
      at the site, officially known as the University of Tennessee, Knoxville's,
      Anthropological Research Facility, are already beginning to land criminals behind
      bars.

PMID- 10960315
TI  - Biological control of invading species.

PMID- 10960314
TI  - Balancing biomedicine's postdoc exchange rate.

PMID- 10960316
TI  - Weighing the benefits of new Alzheimer's treatments.

PMID- 10960317
TI  - Educators have hard choices; nationally, not just in Kansas.

PMID- 10960318
TI  - Intellectual property. Coauthorship and coinventorship.
AB  - Although the accepted criteria used for inclusion as author or inventor are
      similar, the average number of authors in scientific articles is significantly
      higher than the number of inventors on the corresponding patents. This finding
      can be attributed to an artificial inflation of coauthors, to the exclusion of
      coinventors, or--more probably--to a mix of both causes. This article argues that
      the discrepancy between the numbers of coauthors and inventors can have
      significant legal consequences, as the exclusion of an inventor can render a U.S.
      patent invalid or seriously harm its value. A proposal aiming to avoid such
      consequences and taking into account legal as well as authorship credit
      considerations is described.

PMID- 10960319
TI  - Structural biology. The ribosome is a ribozyme.
AB  - Ribosomes, the cellular factories that manufacture proteins, contain both RNA and
      protein, but exactly how all of the different ribosomal components contribute to
      protein synthesis is still not clear. Now, as Thomas Cech explains in his
      Perspective, atomic resolution of the structure of the large ribosomal subunit
      reveals that, as predicted by those convinced of a prebiotic RNA world, RNA is
      the catalytic component with proteins being the structural units that support and
      stabilize it (Ban et al., Nissen et al., Muth et al.).

PMID- 10960320
TI  - Immunology. Lymphocyte survival--ignorance is BLys.
AB  - As if the TNF receptor and ligand superfamily was not big enough, two new
      receptors and their ligands have now been added to it. As Laabi and Strasser
      explain in their Perspective, the receptors BCMA and TACI and their ligands
      BAFF/BLys and APRIL, respectively, are important for B lymphocyte survival,
      proliferation, and differentiation.

PMID- 10960321
TI  - Bibliography of toxinology.

PMID- 10960323
TI  - Case 6: Renovascular hypertension.
AB  - Renovascular hypertension is a progressive disorder that can result in serious
      complications without adequate treatment. Unfortunately, identification of
      patients with the condition is often difficult, and the optimal approach to
      management continues to be debated.

PMID- 10960322
TI  - Re: Field evaluation of the clinical effectiveness of vaccines against pertusis,
      measles, rubella, and mumps.

PMID- 10960325
TI  - [Neurohypophyseal regulation of osmoregulator systems].

PMID- 10960324
TI  - Dispersion in electrocardiography has become epidemic.

PMID- 10960326
TI  - Biochemical mechanism of apoptotic execution.

PMID- 10960327
TI  - The cell and molecular biology of apoptosis in T-lymphocytes.

PMID- 10960328
TI  - [Molecular basis of hyperinsulinisms].

PMID- 10960329
TI  - [Uncoupling proteins and energy metabolism].

PMID- 10960330
TI  - The child born small: an endocrine challenge.

PMID- 10960331
TI  - Recognition of a new association: reduced fetal growth, precocious pubarche,
      hyperinsulinism and ovarian dysfunction.

PMID- 10960332
TI  - [Emergency contraception].

PMID- 10960334
TI  - Dietary products used in infants for treatment and prevention of food allergy.

PMID- 10960333
TI  - [Amiloride-sensitive sodium channel in the nephron and its activation by
      vasopressin].

PMID- 10960335
TI  - Fits, pyridoxine, and hyperprolinaemia type II.

PMID- 10960336
TI  - Gastrointestinal symptoms in asthmatic patients.

PMID- 10960337
TI  - Health care needs for travellers.

PMID- 10960338
TI  - Intraosseous access in infant resuscitation.

PMID- 10960340
TI  - Natural history of glutaric aciduria type 1.

PMID- 10960341
TI  - Palivizumab and RSV prevention.

PMID- 10960339
TI  - LHRH analogue and growth hormone did not improve the final height of a patient
      with juvenile hypothyroidism accompanied by precocious puberty.

PMID- 10960342
TI  - Palivizumab and RSV prevention.

PMID- 10960343
TI  - Intravesical haemorrhage: a rare late manifestation of vitamin K deficiency.

PMID- 10960344
TI  - Fibrogenesis. III. Posttranscriptional regulation of type I collagen.
AB  - There are several independent metabolic steps that determine the level of a
      protein in eukaryotic cells. The steady-state level of the mRNA encoding the
      specific protein is determined by rate of transcription, percentage of
      transcripts that are ultimately processed and transported to the cytoplasm, and
      half-life of the mRNA in cytoplasm. The amount of protein that accumulates from a
      particular transcript is influenced not only by the amount of mRNA present in the
      cytoplasm but also by the rate of translation of the mRNA and stability of the
      protein product. There is compelling evidence that the steady-state level of many
      proteins is regulated at multiple steps, and when there is a large change in the
      amount of either mRNA or protein it is likely that multiple steps in the
      metabolism of the mRNA and protein have been altered. In the case of type I
      collagen production in the fibrotic liver, recent work has shown that there is
      regulation of multiple steps resulting in an approximately 70-fold increase in
      collagen production by the hepatic stellate cells. In addition to the well
      documented relatively small effect on transcription, there are effects on
      processing/transport of the mRNA, translation of the mRNA, and stability of the
      mRNA. Large changes of protein levels are produced by altering the rates or
      efficiency of multiple steps. The molecular details of some of these
      posttranscriptional regulatory events are currently being elucidated. Here we
      review the various potential steps for regulation in the synthesis of a protein
      and discuss how the synthesis of type I collagen may be regulated in the fibrotic
      liver.

PMID- 10960345
TI  - Molecular physiology and pathophysiology of tight junctions. I. Biogenesis of
      tight junctions and epithelial polarity.
AB  - The tight junction (TJ) was first noticed through its ability to control
      permeation across the paracellular route, but the homologies of its molecular
      components with peptides that participate in tumor suppression, nuclear
      addressing, and cell proliferation indicate that it may be involved in many other
      fundamental functions. TJs are formed by a dozen molecular species that assemble
      through PDZ and other protein-protein clustering promoting sequences, in response
      to the activation of E-cadherin. The TJ occupies a highly specific position
      between the apical and the basolateral domains. Its first molecular components
      seem to be delivered to such a position by addressing signals in their molecule
      and, once anchored, serve as a clustering nucleus for further TJ-associated
      molecules. Although in mature epithelial cells TJs and E-cadherin do not
      colocalize, a complex chain of reactions goes from one to the other that involves
      alpha-, beta-, and gamma-catenins, two different G proteins, phospholipase C,
      protein kinase C, calmodulin, mitogen-activated protein kinase, and molecules
      pertaining to the cytoskeleton, which keep the TJ sensitive to physiological
      requirements and local conditions (notably to Ca(2+)-dependent cell-cell
      contacts) throughout the life of the epithelium.

PMID- 10960346
TI  - Endothelin-1-induced PMN infiltration and mucosal dysfunction in the rat small
      intestine.
AB  - The objectives of this study were to characterize the effects of endothelin (ET)
      1 on intestinal mucosal parameters and to assess the contribution of
      polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1),
      and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET
      1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into
      the superior mesenteric artery for 10 min, and tissue samples were obtained 30
      min after terminating the infusion. ET-1 administration significantly elevated
      tissue myeloperoxidase activity, plasma carbonyl content, and tissue
      chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and
      oxidant stress. Blood-to-lumen clearance of (51)Cr-EDTA significantly increased
      after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2
      mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated
      the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that
      ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat
      small intestine and that ET-1-induced mucosal dysfunction involves a mechanism
      that includes a role for PMNs, ICAM-1, and PAF.

PMID- 10960347
TI  - Identification of genes involved in mucosal defense and inflammation associated
      with normal enteric bacteria.
AB  - Normal luminal bacteria and their products play a role in experimental colitis
      and inflammatory bowel disease. However, what molecules from what cells are
      responsible for mounting and maintaining the mucosal defense against luminal
      flora is still uncertain. The aim of this study was to identify epithelial gene
      products involved in mucosal defense and inflammation associated with ubiquitous
      enteric bacteria. Germ-free ICR mice were given an oral bacterial suspension
      prepared from conventional components (bacterial reconstitution). Small
      intestinal and colonic epithelial cells were isolated from bacteria
      reconstituted, germ-free, and specific pathogen-free mice. Differential gene
      expression was investigated by differential display, Northern blot, and sequence
      analysis. Bacterial reconstitution resulted in acute but self-limited colitis. In
      epithelial cells, we observed the induction of small intestine-specific genes of
      the cryptdin family and colon-specific expression of serum amyloid A1 gene. This
      novel approach allows the identification of known and novel gene products
      involved in mucosal defense against luminal microorganisms and the associated
      inflammatory response.

PMID- 10960348
TI  - Characterization of mouse A33 antigen, a definitive marker for basolateral
      surfaces of intestinal epithelial cells.
AB  - The murine A33 antigen is emerging as a definitive marker of intestinal
      epithelial cells. Cloning and sequence determination of cDNAs encoding mA33
      antigen predict a novel type 1 transmembrane protein of 298 amino acids,
      comprising an extracellular domain with two immunoglobulin-like domains, a single
      span transmembrane domain, and a highly acidic cytoplasmic domain. On the basis
      of conservation of amino acid sequence and genomic structure, the mA33 antigen is
      a member of a growing subfamily within the immunoglobulin superfamily, which
      includes transmembrane proteins CTX/ChT1, CTM/CTH, and CAR. During embryonic
      development, mA33 antigen expression is first observed in the inner cell mass of
      blastocysts before implantation. Intestinal expression of mA33 antigen is
      initiated in the hindgut at E14.5 and increases steadily throughout late
      embryonic and postnatal life into adulthood. The protein is specifically
      expressed on the basolateral surfaces of intestinal epithelial cells of all
      lineages, independent of their position along the rostrocaudal and crypt-villus
      axes. Thus the mA33 antigen appears to be a novel marker for both proliferating
      and differentiating intestinal epithelial cells.

PMID- 10960349
TI  - Neural regulation of intestinal smooth muscle growth in vitro.
AB  - The loss of intrinsic neurons is an early event in inflammation of the rat
      intestine that precedes the growth of intestinal smooth muscle cells (ISMC). To
      study this relationship, we cocultured ISMC and myenteric plexus neurons from the
      rat small intestine and examined the effect of scorpion venom, a selective
      neurotoxin, on ISMC growth. By 5 days after neuronal ablation, ISMC number
      increased to 141+/-13% (n = 6) and the uptake of [(3)H]thymidine in response to
      mitogenic stimulation was nearly doubled. Atropine caused a dose-dependent
      increase in [(3)H]thymidine uptake in cocultures, suggesting the involvement of
      neural stimulation of cholinergic receptors in regulation of ISMC growth. In
      contrast, coculture of ISMC with sympathetic neurons increased [(3)H]thymidine
      uptake by 45-80%, which was sensitive to propranolol (30 microM) and was lost
      when the neurons were separated from ISMC by a permeable filter. Western blotting
      showed that coculture with myenteric neurons increased alpha-smooth muscle
      specific actin nearly threefold to a level close to ISMC in vivo. Therefore,
      factors derived from enteric neurons maintain the phenotype of ISMC through
      suppression of the growth response, whereas catecholamines released by neurons
      extrinsic to the intestine may stimulate their growth. Thus inflammation-induced
      damage to intestinal innervation may initiate or modulate ISMC hyperplasia.

PMID- 10960350
TI  - Error analysis of classic colonic transit time estimates.
AB  - Estimates of colonic transit times (CTT) through the three colonic segments,
      right colon, left colon, and rectosigmoid, are commonly based on radiopaque
      markers. For a given segment, CTT is usually calculated from just the number of
      markers visible in that segment on abdominal X-rays. This procedure is only
      strictly valid for the theoretical, but unrealistic, case of continuous marker
      ingestion (i. e., not for a single or once-daily ingestion). CTT was analyzed
      using the usual estimate of the mean CTT of one marker and also using a new, more
      realistic estimate based on the kinetic coefficients of a three-compartment
      colonic model. We directly compared our compartmental approach to classic CTT
      estimates by double-marker studies in six patients. We also retrospectively
      studied CTT in 148 healthy control subjects (83 males, 65 females) and 1,309
      subjects with functional bowel disorders (irritable bowel syndrome or
      constipation). Compared with the compartmental estimates, the classic approach
      systematically underestimates CTT in both populations, i.e., in patients and in
      healthy control subjects. The relative error could easily reach 100% independent
      of the site of colonic transit delay. The normal values of total CTT are then
      44.3+/-29.3 instead of 30.1+/-23.6 h for males and 68.2+/-54.4 instead of 47.1+/
      28.2 h for females.

PMID- 10960351
TI  - Presynaptic nicotinic acetylcholine receptors in the myenteric plexus of guinea
      pig intestine.
AB  - Presynaptic nicotinic acetylcholine receptors (nAChRs) were studied in myenteric
      plexus preparations from guinea pig ileum using intracellular
      electrophysiological methods. Microapplication of nicotine (1 mM) caused a
      biphasic depolarization in all AH neurons (n = 30) and in 36 of 49 S neurons.
      Cytisine (1 mM) caused fast depolarizations in S neurons and no response in AH
      neurons. Mecamylamine (10 microM) blocked all responses caused by nicotine and
      cytisine. TTX (0.3 microM) blocked slow excitatory synaptic potentials in S and
      AH neurons but had no effect on fast depolarizations caused by nicotine. Nicotine
      induced slow depolarizations were reduced by TTX in two of twelve AH neurons (79%
      inhibition) and four of nine S neurons (90+/-12% inhibition). Slow nicotine
      induced depolarizations in the remaining neurons were TTX resistant. TTX
      resistant slow depolarizations were inhibited after neurokinin receptor 3
      desensitization caused by senktide (0.1 microM); senktide desensitization
      inhibited the slow nicotine-induced depolarization by 81+/-5% and 63+/-15% in AH
      and S neurons, respectively. A low-calcium and high-magnesium solution blocked
      nicotine-induced slow depolarizations in AH neurons. In conclusion, presynaptic
      nAChRs mediate the release of substance P and/or neurokinin A to cause slow
      depolarizations of myenteric neurons.

PMID- 10960352
TI  - Novel nuclear corticosteroid binding in rat small intestinal epithelia.
AB  - When small intestinal epithelial cells are incubated with [(3)H]corticosterone,
      nuclear binding is displaced neither by aldosterone nor RU-28362, suggesting that
      [(3)H]corticosterone is binding to a site distinct from mineralocorticoid
      receptor and glucocorticoid receptor. Saturation and Scatchard analysis of
      nuclear [(3)H]corticosterone binding demonstrate a single saturable binding site
      with a relatively low affinity (49 nM) and high capacity (5 fmol/microg DNA).
      Competitive binding assays indicate that this site has a unique steroid binding
      specificity, which distinguishes it from other steroid receptors. Steroid
      specificity of nuclear binding mirrors inhibition of the low 11beta-dehydrogenase
      activity, suggesting that binding may be to an 11beta-hydroxysteroid
      dehydrogenase (11betaHSD) isoform, although 11betaHSD1 is not present in small
      intestinal epithelia and 11betaHSD2 does not colocalize intracellularly with the
      binding site. In summary, a nuclear [(3)H]corticosterone binding site is present
      in small intestinal epithelia that is distinct from other steroid receptors and
      shares steroid specificity characteristics with 11betaHSD2 but is distinguishable
      from the latter by its distinct intracellular localization.

PMID- 10960353
TI  - In vivo changes in the intestinal reflexes and the response to CCK in the
      inflamed small intestine of the rat.
AB  - Functional motor changes and morphological alterations have been associated with
      intestinal inflammation. The aim of our study was to evaluate functional
      alterations of intestinal reflexes and of the responses to CCK in the Trichinella
      spiralis model of intestinal inflammation. Rats were prepared with strain gauges
      and electrodes in the small intestine to evaluate spontaneous motor activity, the
      ascending contraction of the peristaltic reflex, and the motor responses to CCK-8
      infusion. Infected animals showed increased motor activity at the duodenum and
      jejunum but not at the ileum. Ascending contraction was increased in both
      duodenum and ileum. Ascending excitation after N(omega)-nitro-L-arginine was
      still increased as well as the residual response after atropine. Response to CCK
      8 during intestinal inflammation was changed in the jejunum, in which it turned
      from the inhibition shown in healthy animals to excitation. NADPH-diaphorase
      staining did not show any changes between distribution and density of positive
      neurons in either healthy or infected animals. In conclusion, intestinal
      inflammation induces functional changes in the motor activity that could explain
      the abnormal motor responses observed in inflammatory disorders.

PMID- 10960354
TI  - The metabolism of gastrin-52 and gastrin-6 in pigs.
AB  - The kinetics and metabolism in various organs of three bioactive products of
      progastrin, the small sulfated and nonsulfated gastrin-6 and the large
      nonsulfated gastrin-52, were examined during intravenous administration in
      anesthetized pigs. The kidney, hindlimb, liver, head, and gut eliminated the
      hexapeptides efficiently, with a fractional extraction ranging from 0.50 to 0.28
      (P<0.001-0.05). No metabolism was recorded in the lungs, and sulfation was
      without influence on the extraction of gastrin-6. Gastrin-52 was eliminated only
      in the kidney and the head, with a fractional extraction between 0.23 and 0.11
      (P<0.01-0.05). The half-life of sulfated and nonsulfated gastrin-6 was 1.5+/-0.4
      and 1.4+/-0.3 min, the metabolic clearance rate (MCR) was 80.8+/-7.6 and 116.0+/
      13.5 ml x kg(-1) x min(-1) (P<0.05), and the apparent volume of distribution
      (V(dss)) was 199.3+/-70.1 and 231.4+/-37.3 ml/kg, respectively. The decay of
      gastrin-52 in plasma was biexponential. The half-lives of this biexponential
      after a bolus injection were 3.9+/-0.5 (T(1/2alpha)) and 25.7+/-1.4 (T(1/2beta))
      min, and the MCR and V(dss) were 4.2+/-0.4 ml. kg(-1) x min(-1) and 116.2+/-16.2
      ml/kg(1). We conclude that there is a differential elimination of progastrin
      products in splanchnic and nonsplanchnic tissue, which depends on the chain
      length of the peptides. Sulfation of gastrin-6 had no influence on the organ
      specific extraction but reduced the MCR. Our results are in keeping with previous
      studies of nonsulfated gastrin-17, which is extracted in the kidney, head, limb,
      and gut but not in the liver.

PMID- 10960355
TI  - Regulation of glucose-dependent insulinotropic polypeptide release by protein in
      the rat.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) release has been demonstrated
      predominantly after ingestion of carbohydrate and fat. These studies were
      conducted to determine the effects of protein on GIP expression in the rat.
      Whereas no significant changes in duodenal mucosal GIP mRNA levels were detected
      in response to peptone, the duodenal GIP concentration increased from 8.4+/-1.5
      to 19.8+/-3.2 ng GIP/mg protein at 120 min (P<0.01). Plasma GIP levels also
      increased from 95+/-5.2 pg/ml to a peak of 289+/-56.1 pg/ml at 120 min (P<0.01).
      To determine whether the effects of protein on GIP were due to stimulation of
      acid secretion, rats were pretreated with 10 mg/kg omeprazole, after which
      mucosal and plasma GIP concentrations were partially attenuated. To further
      examine the effects of luminal acid, rats were administered intraduodenal 0.1 M
      HCl for 120 min, which significantly enhanced GIP expression. These studies
      indicate that nutrient protein provides a potent stimulus for GIP expression in
      the rat, an effect that occurs at the posttranslational level and may be mediated
      in part through the acid-stimulatory properties of protein. The effects of acid
      on GIP are consistent with a role for GIP as an enterogastrone in the rat.

PMID- 10960356
TI  - Role of cGMP as a mediator of nerve-induced motor functions of the opossum
      esophagus.
AB  - Stimulation of esophageal nerves produces biphasic relaxation of the lower
      esophageal sphincter (LES) and an off response of circular esophageal muscle.
      Previously, we proposed that cGMP mediates nerve-induced hyperpolarization of
      circular LES muscle but not LES relaxation. These experiments explore whether
      cGMP mediates LES relaxation or the off response. Strips of muscle from the
      opossum esophagus and LES were connected to force-displacement transducers,
      placed in tissue baths containing oxygenated Krebs solution at 37 degrees C, and
      stimulated by an electrical field. 1H-[1,2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one
      (ODQ), a selective inhibitor of guanylyl cyclase, antagonized the off response,
      shortened its latency, and blocked the first phase of LES relaxation. ODQ also
      antagonized LES relaxation by exogenous nitric oxide (NO) but not relaxations by
      vasoactive intestinal polypeptide (VIP). Part of the nerve-induced LES relaxation
      and the off response appear to be mediated by the second messenger cGMP. These
      studies indicate that VIP-induced LES relaxation is not mediated by cGMP and
      therefore do not support the hypothesis that VIP produces LES relaxation by
      causing the generation of NO.

PMID- 10960357
TI  - Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by
      acting in the brain.
AB  - The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally
      stimulated gastric acid secretion was studied using immunoneutralization with PYY
      antibody in urethan-anesthetized rats. Gastric acid secretion (59+/-7 micromol/90
      min) stimulated by intracisternal injection of the stable thyrotropin-releasing
      hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by
      52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol. kg(-1) x h(
      1) PYY, respectively. PYY or PYY(3-36) (2.4 pmol/rat) injected intracisternally
      also inhibited the acid response to intracisternal RX-77368 by 73% and 80%,
      respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which
      shows a 35% cross-reaction with PYY(3-36) by RIA, completely prevented the
      inhibitory effect of intravenously infused PYY (1 nmol x kg(-1) x h(-1)). When
      injected intracisternally, the PYY antibody (280 microg/rat) reversed
      intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol x kg(-1) x h(-1))
      induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%,
      respectively. These results provide supporting evidence that peripheral PYY
      inhibits central vagal stimulation of gastric acid secretion through an action in
      the brain.

PMID- 10960358
TI  - TNF-alpha activates solitary nucleus neurons responsive to gastric distension.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is liberated as part of the immune
      response to antigenic challenge, carcinogenesis, and radiation therapy. Previous
      studies have implicated elevated circulating levels of this cytokine in the
      gastric hypomotility associated with these disease states. Our earlier studies
      suggest that a site of action of TNF-alpha may be within the medullary dorsal
      vagal complex. In this study, we describe the role of TNF-alpha as a
      neuromodulator affecting neurons in the nucleus of the solitary tract that are
      involved in vago-vagal reflex control of gastric motility. The results presented
      herein suggest that TNF-alpha may induce a persistent gastric stasis by
      functioning as a hormone that modulates intrinsic vago-vagal reflex pathways
      during illness.

PMID- 10960360
TI  - Demonstration of a pH gradient in the gastric gland of the acid-secreting guinea
      pig mucosa.
AB  - The gastric mucosa is covered by a continuous layer of mucus. Although important
      for understanding the mechanism of this protective function, only scarce
      information exists about the pH inside the gastric gland and its outlet. pH in
      the lumen of the gastric glands, in the outlet of gastric crypts, and in the
      adjacent cells was measured in the isolated acid-secreting mucosa of the guinea
      pig. Ultrafine double-barreled pH microelectrodes were advanced at high
      acceleration rates through the gastric mucus and the tissue to ensure precise
      intracellular and gland lumen pH measurements. A pH gradient was found to exist
      along the gastric gland, where the pH is 3.0 at parietal cells, i.e., in the
      deepest regions, and increases to 4.6 at the crypt outlet. Intracellular pH
      (pH(i)) of epithelial cells bordering a crypt outlet, and of neck cells bordering
      a gland, was acidic, averaging 6.0 and 6.5, respectively. pH(i) of deep cells
      bordering a gland was nearly neutral, averaging 7.1, and the secreting parietal
      cells were characterized by a slightly alkaline pH(i) of 7.5. This gland pH
      gradient is in general agreement with a model that we recently proposed for
      proton transport in the gastric mucus, in which protons secreted by the parietal
      cells are buffered to and transported with the simultaneously secreted mucus
      toward the gastric lumen, where they are liberated from the degraded mucus.

PMID- 10960359
TI  - Rotavirus infection impairs intestinal brush-border membrane Na(+)-solute
      cotransport activities in young rabbits.
AB  - The mechanism of rotavirus diarrhea was investigated by infecting young, specific
      pathogen-free, New Zealand rabbits with a lapine rotavirus, strain La/RR510. With
      4-wk-old animals, virus shedding into the intestinal lumen peaked at 72 h
      postinfection (hpi), and a mild, watery diarrhea appeared at 124 hpi. No
      intestinal lesions were seen up to 144 hpi, indicating that diarrhea does not
      follow mucosal damage but can precede it, as if cell dysfunction were the cause,
      not the consequence, of the histological lesions. Kinetic analyses with brush
      border membrane vesicles isolated from infected rabbits revealed strong
      inhibition of both Na(+)-D-glucose (SGLT1) and Na(+)-L-leucine symport
      activities. For both symporters, only maximum velocity decreased with time. The
      density of phlorizin-binding sites and SGLT1 protein antigen in the membrane
      remained unaffected, indicating that the virus effect on this symporter is
      direct. Because SGLT1 supports water reabsorption under physiological conditions,
      the mechanism of rotavirus diarrhea may involve a generalized inhibition of Na(+)
      solute symport systems, hence, of water reabsorption. Massive water loss through
      the intestine may eventually overwhelm the capacity of the organ for water
      reabsorption, thereby helping the diarrhea to get established.

PMID- 10960361
TI  - Control of CCK gene transcription by PACAP in STC-1 cells.
AB  - The mechanisms by which neuroendocrine stimulants regulate CCK gene transcription
      are unclear. We examined promoter activation by pituitary adenylate cyclase
      activating polypeptide (PACAP), a known CCK secretagogue, in the enteroendocrine
      cell line STC-1. The promoter region from -70 to -87 bp, relative to the
      transcriptional start site, contains a composite calcium/cyclic AMP response
      element (CRE)/activator protein 1 (AP1) site that may bind CRE binding protein
      (CREB) and AP1. PACAP (with IBMX) stimulated expression of an 87-bp construct
      3.35+/-0.36-fold but had no effect on a -70 construct. The effect was blocked by
      the protein kinase A inhibitor H-89 and by a dominant-negative CREB plasmid.
      Mutation of the CRE/AP1 site to a canonical CRE site did not affect the response
      to PACAP, but mutation to a canonical AP1 site prevented it. CREB phosphorylation
      was increased after PACAP treatment. Electrophoretic mobility shift assay and
      supershift analysis revealed that CREB and not AP1 bound to the CRE/AP1 site and
      that PACAP increased the proportion of phosphorylated CREB that was bound. We
      conclude that PACAP increases CCK gene expression via a cAMP-mediated pathway
      involving CREB phosphorylation by protein kinase A and activation of a composite
      CRE/AP1 site.

PMID- 10960362
TI  - PRL-1 PTPase expression is developmentally regulated with tissue-specific
      patterns in epithelial tissues.
AB  - The mechanisms controlling tyrosine phosphorylation of cellular proteins are
      important in the regulation of many cellular processes, including development and
      differentiation. Protein tyrosine phosphatases (PTPases) may be as important as
      protein tyrosine kinases (PTKs) in these processes. PRL-1 is a distinct PTPase
      originally identified as an immediate-early gene in liver regeneration whose
      expression is associated with growth in some tissues but with differentiation in
      others. We now demonstrate that the PRL-1 protein is expressed during development
      in a number of digestive epithelial tissues. It is expressed at variable time
      points in the developing intestine, but its expression is limited to the
      developing villus enterocytes. In the gastric epithelium, PRL-1 expression in the
      adult is restricted to zymogen cells. PRL-1 is also expressed in the developing
      liver and esophagus and in the epithelia of the kidney and lung. In each of these
      contexts, the expression of PRL-1 is associated with terminal differentiation,
      suggesting that it may play a role in this important developmental process.

PMID- 10960363
TI  - Actions of histamine on muscle and ganglia of the guinea pig gallbladder.
AB  - Histamine is an inflammatory mediator present in mast cells, which are abundant
      in the wall of the gallbladder. We examined the electrical properties of
      gallbladder smooth muscle and nerve associated with histamine-induced changes in
      gallbladder tone. Recordings were made from gallbladder smooth muscle and
      neurons, and responses to histamine and receptor subtype-specific compounds were
      tested. Histamine application to intact smooth muscle produced a concentration
      dependent membrane depolarization and increased excitability. In the presence of
      the H(2) antagonist ranitidine, the response to histamine was potentiated.
      Activation of H(2) receptors caused membrane hyperpolarization and elimination of
      spontaneous action potentials. The H(2) response was attenuated by the ATP
      sensitive K(+) (K(ATP)) channel blocker glibenclamide in intact and isolated
      smooth muscle. Histamine had no effect on the resting membrane potential or
      excitability of gallbladder neurons. Furthermore, neither histamine nor the H(3)
      agonist R-alpha-methylhistamine altered the amplitude of the fast excitatory
      postsynaptic potential in gallbladder ganglia. The mast cell degranulator
      compound 48/80 caused a smooth muscle depolarization that was inhibited by the
      H(1) antagonist mepyramine, indicating that histamine released from mast cells
      can activate gallbladder smooth muscle. In conclusion, histamine released from
      mast cells can act on gallbladder smooth muscle, but not in ganglia. The
      depolarization and associated contraction of gallbladder smooth muscle represent
      the net effect of activation of both H(1) (excitatory) and H(2) (inhibitory)
      receptors, with the H(2) receptor-mediated response involving the activation of
      K(ATP) channels.

PMID- 10960364
TI  - Transplanted reporter cells help in defining onset of hepatocyte proliferation
      during the life of F344 rats.
AB  - Transplanted hepatocytes integrate in the liver parenchyma and exhibit gene
      expression patterns that are similar to adjacent host hepatocytes. To determine
      the fate of genetically marked hepatocytes in the context of hepatocellular
      proliferation throughout the rodent life span, we transplanted Fischer 344 (F344)
      rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. The
      proliferative activity in transplanted hepatocytes was studied in animals ranging
      in age from a few days to 2 yr. Transplanted hepatocytes proliferated during
      liver development between 1 and 6 wk of age, each dividing an estimated two to
      five times. DNA synthesis in occasional cells was demonstrated by localizing
      bromodeoxyuridine incorporation. There was no evidence for transplanted cell
      proliferation between 6 wk and 1 yr of age. Subsequently, transplanted cells
      proliferated again, with increased sizes of transplanted cell clusters at 18 and
      24 mo of age. The proliferative activity of transplanted cells was greater in
      rats entering senescence compared with during postnatal liver development. In old
      rats, some liver lobules were composed entirely of transplanted cells. We
      conclude that hepatocyte proliferation in the livers of very young and old F344
      rats is regulated in a temporally determined, biphasic manner. The findings will
      be relevant to mechanisms concerning liver development, senescence, and
      oncogenesis, as well as to cell and gene therapy.

PMID- 10960366
TI  - Intrathecal nalbuphine after cesarean delivery: are we ready?

PMID- 10960367
TI  - An evaluation of prosthetic aortic valves using transesophageal echocardiography:
      the double-envelope technique.
AB  - The conventional continuity equation uses nonsimultaneous measurements of blood
      flow velocities through the left ventricular outflow tract and across the aortic
      valve to calculate aortic valve area (AVA). We have noted that both velocities
      can be simultaneously obtained from continuous wave (CW) Doppler analysis (double
      envelope [DE]). We hypothesize that prosthetic AVA can be calculated by using the
      DE technique, during transesophageal echocardiography (TEE). Prosthetic AVA was
      calculated in 41 of 45 patients immediately after aortic valve replacement by
      using the DE/AVA technique. Left ventricular outflow tract diameter was obtained
      from an esophageal view, while subvalvular (V(1)) and valvular (V(2)) peak
      velocities were simultaneously obtained from transgastric views by using CW
      Doppler. Prosthetic AVA and V(1)/V(2) ratio (Doppler velocity index) were
      calculated. V(1) was also measured by using pulse wave Doppler, as is
      conventionally done. Twenty-three Carbomedic (CM) and 18 Carpentier-Edwards (CE)
      AVA were evaluated. DE/AVAs for CM and CE valves correlated and agreed with that
      reported by the manufacturer (CM r(2) = 0.91, mean bias -0.25 cm(2) [SD 0.18]; CE
      r(2) = 0.73, mean bias -0.02 cm(2) [SD 0.27]). Calculated Doppler velocity index
      values agree with available data (mean bias 0.03 [SD 0.05]). The V(1) obtained by
      using the DE method was nearly identical to the V(1) obtained by using pulse wave
      (r(2) = 0.95, mean bias 0.02 m/s [SD 0.04 m/s]). TEE assessment of prosthetic AVA
      using the DE technique agrees with data reported by the manufacturer. Obtaining
      subvalvular and valvular velocities from the same CW Doppler trace may simplify
      the continuity equation and help avoid errors caused by beat-to-beat changes in
      blood flow. Quantitative prosthetic aortic valve assessment can be performed, on
      line, with TEE by using the DE technique. IMPLICATIONS: Quantitative assessment
      of prosthetic aortic valve area can be performed on-line by using transesophageal
      echocardiography using the double envelope technique.

PMID- 10960365
TI  - Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of
      chronic colitis.
AB  - Crohn's disease is a chronic disease characterized by oxidant-induced tissue
      injury and increased intestinal permeability. A consequence of oxidative damage
      is the accumulation of DNA strand breaks and activation of poly(ADP-ribose)
      polymerase (PARP), which subsequently catalyzes ADP-ribosylation of target
      proteins. In this study, we assessed the role of PARP in the colitis seen in
      interleukin (IL)-10 gene-deficient mice. IL-10 gene-deficient mice demonstrated
      significant alterations in colonic cellular energy status in conjunction with
      increased permeability, proinflammatory cytokine release, and nitrosative stress.
      After 14 days of treatment with the PARP inhibitor 3-aminobenzamide, IL-10 gene
      deficient mice demonstrated normalized colonic permeability; reduced tumor
      necrosis factor-alpha and interferon-gamma secretion, inducible nitric oxide
      synthase expression, and nitrotyrosine levels; and significantly attenuated
      inflammation. Time course studies demonstrated that 3-aminobenzamide rapidly
      altered cellular metabolic activity and decreased cellular lactate levels. This
      was associated with normalization of colonic permeability and followed by a
      downregulation of proinflammatory cytokine release. Our data demonstrate that
      inhibition of PARP activity results in a marked improvement of colonic
      inflammatory disease and a normalization of cellular metabolic function and
      intestinal permeability.

PMID- 10960369
TI  - Continuous positive airway pressure at 10 cm H(2)O during cardiopulmonary bypass
      improves postoperative gas exchange.
AB  - Postbypass pulmonary dysfunction including atelectasis and increased shunting is
      a common problem in the intensive care unit. Negative net fluid balance and
      continuous positive airway pressure (CPAP) have been used to reduce the adverse
      effects of cardiopulmonary bypass (CPB) on the lung. To determine whether CPAP at
      10 cm H(2)O during CPB results in improved postoperative gas exchange in
      comparison with deflated lungs during CPB, we examined 14 patients scheduled for
      elective cardiac surgery. Seven patients received CPAP at 10 cm H(2)O during CPB,
      and in the other seven patients, the lungs were open to the atmosphere (control).
      Measurements were taken before and after CPB, after thoracic closure, and 4 h
      after CPB in the intensive care unit. CPAP at 10 cm H(2)O resulted in
      significantly more perfusion of lung areas with a normal ventilation/perfusion
      distribution (V(A)/Q) and significantly less shunt and low V(A)/Q perfusion 4 h
      after CPB in comparison with the control group. Consequently, arterial oxygen
      partial pressure was significantly higher and alveolar-arterial oxygen partial
      pressure difference was significantly smaller. We conclude that CPAP at 10 cm
      H(2)O during CPB is a simple maneuver that improves postoperative gas exchange.
      IMPLICATIONS: Inflation of the lungs at a pressure of 10 cm H(2)O as compared
      with leaving the lungs deflated during cardiopulmonary bypass was examined. Lung
      inflation during bypass resulted in significantly improved postoperative gas
      exchange.

PMID- 10960368
TI  - Thoracic aorta occlusion-reperfusion decreases hemostasis as assessed by
      thromboelastography in rabbits.
AB  - Perioperative hemorrhage and thrombosis are serious complications associated with
      major vascular surgery. We hypothesized that thoracic aortic occlusion
      reperfusion in rabbits would adversely affect hemostasis as assessed by
      thromboelastographic variables (reaction time, alpha angle and G [a measure of
      clot strength]). Isoflurane-anesthetized rabbits underwent either sham operation
      (n = 10) or 30 min of aortic occlusion followed by 90 min of reperfusion (n =
      10). Blood samples (350 microL) were exposed to 10 microL of either 0.9% NaCl or
      cytochalasin D (a platelet inhibitor, 10 microM final concentration) and analyzed
      for 1 h by using thromboelastography after 30 min of postpreparation
      equilibration and at 30 and 90 min of reperfusion. Aortic occlusion-reperfusion
      resulted in a significant (P: < 0.05) increase in reaction time, decrease in
      alpha angle, and decrease in G at 30 and 90 min of reperfusion compared with the
      sham-operated group. The decrease in hemostatic function after aortic occlusion
      reperfusion was observed to the same degree in samples with or without platelet
      inhibition. There were no significant differences in platelet concentration
      between the sham-operated and aortic occlusion-reperfusion groups. Aortic
      occlusion-reperfusion decreased hemostatic function in rabbits primarily by
      decreasing the coagulation factor-dependent, platelet-independent contribution to
      clotting. IMPLICATIONS: Thoracic aortic occlusion-reperfusion decreased
      hemostatic function in rabbits primarily by decreasing the coagulation factor
      dependent, platelet-independent contribution to clotting. This decrease in
      hemostatic function may contribute to hemorrhagic complications associated with
      major vascular surgery.

PMID- 10960370
TI  - Heparin induces release of phospholipase A(2) into the splanchnic circulation.
AB  - Cardiopulmonary bypass results in increased plasma activity of phospholipase A(2)
      (PLA(2)) that appears to be caused by the administration of heparin. High PLA(2)
      activity may be responsible for increased production of eicosanoids and, thus,
      may be implicated in various pathophysiologic events associated with cardiac
      surgery. To investigate the site of PLA(2) secretion, blood samples were
      simultaneously collected from the radial artery, the pulmonary artery, and the
      hepatic vein at 2, 4, 6, and 20 min after systemic heparinization (350 U/kg).
      Within 2 min of the heparin injection, plasma activity of PLA(2) increased 4- to
      9-fold and remained so for at least 20 min. Two minutes after the heparin
      injection, PLA(2) was significantly higher in the hepatic vein than in the radial
      artery (P: < 0.01). No such difference was detected between pulmonary and radial
      arteries. When heparin was added to blood samples in vitro (5-100 U/mL), plasma
      activity of PLA(2) did not increase, which suggests that the enzyme was not
      secreted by blood cells. IMPLICATIONS: Heparin, given in the dosage required for
      cardiopulmonary bypass, caused release of phospholipase A(2) into the splanchnic
      circulation.

PMID- 10960371
TI  - A quick anti-Xa-activity-based whole blood coagulation assay for monitoring
      unfractionated heparin during cardiopulmonary bypass: a pilot investigation.
AB  - We developed a quick and easy method to perform anti-Xa-activity-based whole
      blood assay and assessed its reliability for online monitoring of unfractionated
      heparins (UFHs) during cardiopulmonary bypass. Seventy-five microliters of a
      mixture of 1:3 large- and small-range Heptest reagent were transferred into blank
      cartridges of the ACT II device. The plastic flags for clot detection and
      stirring the sample and reagent were inserted and overlaid with 75 microL of
      Recalmix for recalcification. One-hundred fifty microliters of citrated whole
      blood were added and measurements performed. In vitro, the linearity of the test
      over a range of 1-8 IU/mL UFH, as well as the influence of variations in
      hematocrit (60%, 30%, and 20%), plasma coagulation factors (50%, 30%, and 20%)
      and platelets (100, 50, and 20 x 10(3)/microL) on the test results were assessed.
      In vivo measurements performed during cardiopulmonary bypass were compared with
      the chromogenic assay. The test revealed linearity to concentrations of 6 IU/mL
      of UFH and was not significantly influenced by the variations in the in vitro set
      up despite a prolongation in samples with a hematocrit of 60%. In vivo, the
      correlation to the chromogenic test was R: = 0.90. The ACT II anti-Xa-UFH assay
      performed in whole blood was reliable when used over a wide range of conditions
      that could be encountered clinically. Although the test is useful for point-of
      care monitoring, the necessity of individual calibrations and pipetting in the
      operation room requires further automation before its use in clinical practice.
      IMPLICATIONS: The ACT II anti-Xa-unfractionated heparin assay allows for reliable
      monitoring of large concentrations of UFH over a wide range of hematocrit,
      platelet, and coagulation factor levels. Further evaluation of this point-of-care
      device is indicated.

PMID- 10960372
TI  - Hematocrit, volume expander, temperature, and shear rate effects on blood
      viscosity.
AB  - Our goal was to determine and predict the effects of temperature, shear rate,
      hematocrit, and different volume expanders on blood viscosity in conditions
      mimicking deep hypothermia for cardiac operations. Blood was obtained from six
      healthy adults. Dilutions were prepared to hematocrits of 35%, 30%, 22.5%, and
      15% using plasma, 0.9% NaCl, 5% human albumin, and 6% hydroxyethyl starch.
      Viscosity was measured over a range of shear rates (4.5-450 s(-1)) and
      temperature (0 degrees -37 degrees C). A parametric expression for predicting
      blood viscosity based on the study variables was developed, and its agreement
      with measured values tested. Viscosity was higher at low shear rates and low
      temperatures, especially at temperatures less than 15 degrees C (P: < 0.016 for
      all conditions in comparison with 37 degrees C). Decreasing hematocrit,
      especially to less than 22.5%, decreased viscosity. Hemodilution with albumin or
      0.9% NaCl decreased blood viscosity more than hemodilution with plasma or 6%
      hydroxyethyl starch (P: < 0.01 for all cases). The derived mathematical model for
      viscosity as a function of temperature, hematocrit, shear rate, and diluent
      predicted viscosity values that correlated well with the measured values in
      experimental samples (r(2) > 0.92, P: < 0.001). IMPLICATIONS: A theoretical model
      for blood viscosity predicted independent effects of temperature, shear rate, and
      hemodilution on viscosity over a wide range of physiologic conditions, including
      thermal extremes of deep hypothermia in an experimental setting. Moderate
      hemodilution to a hematocrit of 22% decreased blood viscosity by 30%-50% at a
      blood temperature of 15 degrees C, suggesting the potential to improve
      microcirculatory perfusion during deep hypothermia.

PMID- 10960374
TI  - The effect of patient positioning on intraabdominal pressure and blood loss in
      spinal surgery.
AB  - Intraabdominal pressure (IAP) can influence blood loss during spinal surgery. We
      examined the relationship of IAP changes to blood loss with a rectal balloon
      pressure catheter. Forty patients were randomly assigned to narrow (Group 1) or
      wide (Group 2) pad support widths of the Wilson frame. IAP was measured when the
      patient was supine after the induction of anesthesia, prone on a gurney, prone on
      the Wilson frame before and after incision, and then, again supine after tracheal
      extubation. IAP in the prone position on the Wilson frame before incision (3.6 cm
      H(2)O) in Group 2 was significantly less than in Group 1 (8.8 cm H(2)O) (P: <
      0.05). Intraoperative blood loss per vertebra in Group 2 (190 +/- 65 mL) was
      significantly less than in Group 1 (381 +/- 236 mL) (P: < 0.05). The correlation
      between blood loss and IAP in the prone position on the Wilson frame in Group 1
      was significant (P: = 0.0022). In conclusion, IAP and intraoperative blood loss
      were significantly less in the wide, than in the narrow, pad support width of the
      Wilson frame. Blood loss tended to increase with an increase in IAP in the narrow
      pad support width of the Wilson frame. IMPLICATIONS: The relationship of
      intraabdominal pressure changes to blood loss were examined with a rectal balloon
      pressure catheter during spinal surgery. Blood loss tended to increase with an
      increase in intraabdominal pressure in the narrow pad support width of the Wilson
      frame.

PMID- 10960375
TI  - Graft failure caused by pulmonary venous obstruction diagnosed by intraoperative
      transesophageal echocardiography during lung transplantation.
AB  - IMPLICATIONS: Intraoperative transesophageal echocardiography can be useful to
      diagnose pulmonary venous anastomotic stenoses during lung transplantation.

PMID- 10960373
TI  - Inhibition by neuromuscular blocking drugs of norepinephrine transporter in
      cultured bovine adrenal medullary cells.
AB  - Pancuronium stimulates the cardiovascular system, whereas vecuronium, a
      derivative of pancuronium, has far fewer effects. The inhibition of
      norepinephrine transporter (NET) in the sympathetic nervous system may partly
      account for the stimulatory actions of pancuronium. To investigate the mechanism
      of action of pancuronium on NET, we examined the effects of pancuronium on NET
      activity by using cultured bovine adrenal medullary cells and compared
      pancuronium with other neuromuscular blocking drugs. Pancuronium (1-300 microM)
      inhibited desipramine-sensitive [(3)H]norepinephrine (NE) uptake in a
      concentration-dependent manner. Vecuronium (100-300 microM) and d-tubocurarine
      (300 microM) also decreased [(3)H]NE uptake but were less potent than pancuronium
      at clinical concentrations. Succinylcholine had little effect on [(3)H]NE uptake.
      Saturation analysis showed that pancuronium and vecuronium reduced an apparent
      maximum velocity (V(max)) of [(3)H]NE uptake without altering Michaelis-Menten
      constant, indicating noncompetitive inhibition. Pancuronium did not inhibit the
      specific binding of [(3)H]desipramine to plasma membranes isolated from bovine
      adrenal medulla. A protein kinase C inhibitor, GF109203X, did not affect the
      inhibition of [(3)H]NE uptake by pancuronium. Pancuronium enhanced the inhibition
      of NET induced by ketamine. These results suggest that pancuronium, with
      clinically relevant concentrations, inhibits NET activity by interacting with a
      site distinct from the recognition site for NE and the desipramine binding site
      on the transporter. IMPLICATIONS: In this study, pancuronium inhibited
      norepinephrine uptake and was the most potent of the neuromuscular blocking drugs
      we tested, including pancuronium, vecuronium, d-tubocurarine, and
      succinylcholine. Pancuronium may affect the sympathetic nervous system by
      inhibiting the activity of the presynaptic norepinephrine transporter at
      clinically relevant concentrations.

PMID- 10960376
TI  - Injury to the abdominal aorta during laparoscopic surgery: an unusual
      presentation.
AB  - IMPLICATIONS: Laparoscopic cholecystectomy is a very common surgical procedure,
      and vascular injuries account for one third of major complications during this
      surgery. We describe an unusual presentation of an abdominal aorta injury.

PMID- 10960377
TI  - Emergence agitation after sevoflurane versus propofol in pediatric patients.
AB  - Sevoflurane may be associated with a high incidence of emergence agitation in
      preschool children. We tested the hypothesis that maintenance of anesthesia with
      propofol after sevoflurane induction would reduce the incidence of this
      excitatory behavior compared with continuing sevoflurane for maintenance. We
      conducted a randomized, single-blinded, two-period, cross-over study in 16
      preschool age children undergoing repeated brief general anesthetics for eye
      examination. After sevoflurane induction, patients were randomly assigned to
      receive either sevoflurane or propofol anesthesia for maintenance. The
      alternative anesthetic was used for the maintenance of anesthesia on the second
      occasion. We compared the speed and quality of recovery characteristics of these
      anesthetics, as well as, overall parent satisfaction with anesthesia. Eight
      patients first received sevoflurane and the remaining eight patients first
      received propofol. Of the patients who received sevoflurane for the maintenance
      of anesthesia, 38% developed emergence agitation. In contrast, none developed
      emergence agitation when propofol was administered for maintenance of anesthesia.
      Despite emergence agitation, sevoflurane provided a shorter postanesthesia care
      unit stay than propofol. Parent satisfaction with anesthesia was greater with
      propofol than with sevoflurane. IMPLICATIONS: In this cross-over study, we
      observed the incidence of emergence agitation with sevoflurane (38%) was
      significantly greater than with propofol (0%) in premedicated, preschool-aged
      children undergoing minor noninvasive surgery.

PMID- 10960378
TI  - Evaluating hemodynamic and T wave criteria of simulated intravascular test doses
      using bupivacaine or isoproterenol in anesthetized children.
AB  - An increase in T wave amplitude > or =25% is a reliable indicator for detecting
      intravascular injection of lidocaine-epinephrine test dose in anesthetized
      children. We examined whether a simulated IV test dose containing bupivacaine
      instead of lidocaine, and isoproterenol instead of epinephrine, produces reliable
      changes in heart rate (HR) and T wave morphology. One hundred healthy infants and
      children (6-72 mo) were randomized to one of five groups (n = 20 each) during 1.0
      minimum alveolar anesthetic concentration sevoflurane and 67% nitrous oxide in
      oxygen: atropine pretreatment (0.01 mg/kg IV) followed by 0.25% bupivacaine
      containing epinephrine 0.5 microg/kg IV, atropine followed by normal saline,
      atropine followed by 1% lidocaine containing isoproterenol 0.1 microg/kg, saline
      pretreatment followed by the lidocaine-isoproterenol test dose, and saline
      followed by saline. HR was recorded every 20 s and T wave amplitude of lead II
      was continuously recorded. All patients receiving the bupivacaine-epinephrine
      test dose and none receiving saline met the HR (positive if > or =10 bpm
      increase) and T wave criteria (positive if > or =25% increase in amplitude). The
      isoproterenol-containing test dose produced positive responses based only on the
      HR criterion with or without atropine pretreatment. Our results indicate that HR
      and T wave changes are useful if a bupivacaine-epinephrine test dose is used and
      that HR is the only useful indicator if an isoproterenol-containing test dose is
      used in sevoflurane-anesthetized children. IMPLICATIONS: To determine if an
      epidurally administered local anesthetic has been unintentionally injected into a
      blood vessel, a small dose of epinephrine or isoproterenol may be added to a
      local anesthetic. We found that an increase in heart rate > or =10 bpm and an
      increase in T wave amplitude of lead II >or =25% are useful indicators for
      detecting accidental intravascular injection of an epinephrine-containing test
      dose in sevoflurane-anesthetized children, whereas only a heart rate change is a
      reliable diagnostic tool if an isoproterenol-containing test dose is used.

PMID- 10960379
TI  - The safety and efficacy of parent-/nurse-controlled analgesia in patients less
      than six years of age.
AB  - Over the past 5 yr, we have treated nonsurgical and postoperative pain in
      children <6 yr of age by using a patient-controlled analgesia pump to deliver
      small-dose continuous IV opioid infusions supplemented by parent- and nurse
      controlled opioid bolus dosing. We call this technique parent-/nurse-controlled
      analgesia (PNCA). Because the safety and efficacy of PNCA have not been
      previously evaluated, we have undertaken a prospective, 1-yr observational study
      to determine patient demographics, effectiveness of analgesia, and the incidence
      of complications (pruritus, vomiting, and respiratory depression) in patients
      receiving PNCA. Data were collected on 212 children (98 female) who were treated
      on 240 occasions with PNCA for episodes of pain. Patients averaged 2.3 +/- 1.7 yr
      of age and 11 +/- 5 kg, and received a median of 4 (range 2-54) days of PNCA
      therapy. Maximum daily pain scores were < or =3/10 (objective pain scale) or < or
      =2/5 (objective or self-report pain scale) in more than 80% of all occasions of
      PNCA use. PNCA usage was associated with an 8% incidence of pruritus and a 15%
      incidence of vomiting on the first day of treatment. Nine children studied
      received naloxone, four (1.7%) for treatment of PNCA-related apnea or
      desaturation. All had improvement in their symptoms after naloxone
      administration. IMPLICATIONS: Parent-/nurse-controlled analgesia provided
      effective pain relief in most children <6 yr of age experiencing nonsurgical or
      postoperative pain. The observed incidence of vomiting and pruritus was similar
      to that seen in older patients treated with patient-controlled analgesia.
      However, significant respiratory depression, although uncommon, did occur, thus
      reinforcing the need for close patient monitoring.

PMID- 10960380
TI  - The anesthetic and recovery profile of two doses (60 and 80 mg) of plain
      mepivacaine for ambulatory spinal anesthesia.
AB  - Reports of transient neurological symptoms with the use of subarachnoid lidocaine
      has generated interest in alternate local anesthetics of intermediate duration,
      such as mepivacaine. This prospective randomized, double-blinded, dose-response
      study examined the anesthetic and recovery profiles of 60- and 80-mg doses of
      preservative-free plain mepivacaine for ambulatory spinal anesthesia. Sixty
      patients undergoing ambulatory anterior cruciate ligament repair of the knee
      under spinal anesthesia were randomized into two groups; Group 1 (29 patients)
      received 4 mL of 1.5% (60-mg dose) and Group 2 (31 patients) received 4 mL of 2%
      (80-mg dose) of plain mepivacaine. All patients received a combined spinal
      epidural anesthetic technique. The epidural catheter was used only in the event
      the surgery outlasted the duration of surgical anesthesia with subarachnoid
      mepivacaine. Epidural supplementation was administered in three patients (12%) in
      Group 1 and one patient (3%) in Group 2 when the sensory block regressed to L-1
      with surgery expected to last longer than 15 min. The cephalad dermatome level of
      the block and degree of motor block was comparable in the two groups. Times to
      two-segment and T-10 regression were comparable in the two groups (112 +/- 26 min
      in Group 1 versus 122 +/- 28 min in Group 2). Time to L-1 regression was
      significantly longer in Group 2 (146 +/- 28 min in Group 1 versus 159 +/- 19 min
      in Group 2). All of the ambulatory milestones were significantly faster in Group
      1. Side effects, such as hypotension and emesis were negligible, severe
      bradycardia and urinary retention did not occur, and none of the patients in the
      two groups reported transient neurological symptoms over 24 h. In conclusion,
      plain mepivacaine in a 60- or 80-mg dose is a suitable local anesthetic choice
      for ambulatory spinal anesthesia with respect to anesthetic, as well as recovery
      profiles. IMPLICATIONS: We evaluated the anesthetic and recovery profiles of 60-
      and 80-mg doses of plain mepivacaine for ambulatory spinal anesthesia. Both doses
      produced comparable sensory and motor block. Sensory and motor regression and
      ambulatory milestones were 20-30 min longer with the 80-mg dose. Side effects
      were negligible and transient neurological symptoms were not reported during a 24
      h follow-up.

PMID- 10960381
TI  - Retrobulbar versus systemic application of morphine during titratable regional
      anesthesia via retrobulbar catheter in intraocular surgery.
AB  - IMPLICATIONS: We investigated the effects of morphine on postoperative pain in
      patients undergoing intraocular surgery using a new indwelling catheter. Although
      morphine produced central analgesic effects, there was no evidence for the
      involvement of peripheral opioid receptors in the modulation of ocular pain.

PMID- 10960382
TI  - Carbon dioxide absorption during extraperitoneal and transperitoneal endoscopic
      hernioplasty.
AB  - Transabdominal preperitoneal (TAPP) or total extraperitoneal (TEP) hernioplasty
      are probably associated with differing degrees of CO(2) absorption which can
      influence anesthetic management and perioperative morbidity. We studied 20
      patients with either TAPP or TEP for perioperative CO(2) absorption (calculated
      from CO(2) elimination and metabolic CO(2) production) and ventilatory changes
      required to maintain normocapnia (blood gas analyses). CO(2) absorption reached
      plateau values in the TAPP group, but increased over time in the TEP group.
      Median CO(2) absorption during insufflation was 61 mL/min (range 43-78) for TAPP
      and 114 mL/min (range 75-178) for TEP, with a maximum of 114 mL/min (range 75
      178) for TAPP and 258 mL/min (range 112-585) for TEP. Median minute ventilation
      (V(E)) required for maintaining normocapnia was 9. 5 L/min (range 7.7-11.5) for
      TAPP and 12.9 L/min (range 9.0-22.6) for TEP (P: < 0.01). Seven patients in the
      TEP group required over 18 L/min V(E), although no patient in the TAPP group
      required more than 14 L/min V(E). All patients in the TEP group had significant
      subcutaneous emphysema resulting in one case of delayed tracheal extubation. We
      conclude that CO(2) absorption is consistently less with TAPP. IMPLICATIONS: The
      greater magnitude of carbon dioxide absorption during total extraperitoneal
      hernioplasty puts an additional load on the lungs and could pose a risk for
      patients with chronic lung disease who might be unable to eliminate excess carbon
      dioxide.

PMID- 10960383
TI  - Spontaneous recovery profile of rapacuronium during desflurane, sevoflurane, or
      propofol anesthesia for outpatient laparoscopy.
AB  - We evaluated the spontaneous recovery characteristics of rapacuronium during
      desflurane-, sevoflurane-, or propofol-based anesthesia in 51 consenting women
      undergoing laparoscopic tubal ligation procedures. After the induction of the
      anesthesia with standardized doses of propofol and fentanyl, 1.5 mg/kg IV
      rapacuronium was administered to facilitate tracheal intubation. Patients were
      randomized to receive either 1 minimum alveolar anesthetic concentration of
      desflurane, 1 minimum alveolar concentration of sevoflurane, or 100 microg. kg(
      1). min(-1) propofol infusion in combination with 66% nitrous oxide in oxygen for
      maintenance of anesthesia. Neuromuscular blockade was monitored at the wrist by
      using electromyography. The degree of maximum blockade and the times for first
      twitch recovery (T(1)) to 5%, 25%, 50%, 75%, and 90%, as well as the recovery
      index, were similar in all three anesthetic groups. However, recovery times for
      the train-of-four ratio to achieve 0.7 and 0.8 were significantly longer with
      desflurane (44.4 +/- 18.9 and 53.5 +/- 22.4 min) and sevoflurane (44.8 +/- 15.1
      and 53.2 +/- 15.8 min) compared with propofol (31.8 +/- 5.3 and 36.5 +/- 6.5
      min). Eight patients (16%) required a maintenance dose of 0.5 mg/kg rapacuronium
      and reversal of rapacuronium residual block occurred in three (6%) patients. We
      conclude that spontaneous recovery after an intubating dose of 1.5 mg/kg
      rapacuronium was significantly prolonged by both desflurane and sevoflurane
      compared with propofol-based anesthesia. Routine monitoring of neuromuscular
      activity is recommended even when a single bolus dose of rapacuronium is
      administered during ambulatory anesthesia. IMPLICATIONS: When administered for
      laparoscopic surgery, the duration of action of an intubating dose of
      rapacuronium was prolonged 40%-50% by desflurane and sevoflurane, respectively,
      (versus propofol). Monitoring recovery of neuromuscular blockade produced by
      rapacuronium is particularly important when desflurane or sevoflurane is
      administered to ensure that an adequate recovery (train-of-four > or = 0.8) is
      achieved by the end of anesthesia.

PMID- 10960384
TI  - Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after
      cesarean delivery: an evaluation of postoperative analgesia and adverse effects.
AB  - We performed a prospective, randomized, double-blinded, multicenter study to
      compare the analgesic efficacy and adverse effects of intrathecal nalbuphine, at
      three different doses, and intrathecal morphine for postoperative pain relief
      after cesarean deliveries. Ninety healthy patients at full term who were
      scheduled for elective cesarean delivery with spinal anesthesia were enrolled in
      the study. They received 10 mg of hyperbaric bupivacaine 0.5% with either
      morphine 0.2 mg (Group 1), nalbuphine 0.2 mg (Group 2), nalbuphine 0. 8 mg (Group
      3), or nalbuphine 1.6 mg (Group 4). Only patients in Groups 1 and 2 reported pain
      during surgery. Postoperative analgesia lasted significantly longer in the
      morphine group, compared with the nalbuphine groups (P: < 0.0001). In the
      nalbuphine groups, postoperative analgesia lasted longest with the 0.8-mg dose.
      The additional increase to 1.6 mg did not increase efficacy. The incidence of
      pruritus was significantly higher in Group 1 (11 of 22), compared with Group 2 (0
      of 22, P: < 0.0002), Group 3 (0 of 23, P: < 0.0001), and Group 4 (3 of 20, P: <
      0.02). Postoperative nausea and vomiting were more frequent in Group 1 (5 of 22),
      compared with Group 2 (0 of 22, P: < 0.05), Group 3 (0 of 23, P: < 0.05), and
      Group 4 (3 of 23, not significant). There was no maternal or newborn respiratory
      depression. Neonatal conditions (Apgar scores and umbilical vein and artery blood
      gas values) were similar for all groups. This study suggests that intrathecal
      nalbuphine 0.8 mg provides good intraoperative and early postoperative analgesia
      without side effects. However, only morphine provides long-lasting analgesia.
      IMPLICATIONS: Small doses of intrathecal nalbuphine produce fewer adverse
      effects, such as pruritus and postoperative nausea and vomiting, compared with
      intrathecal morphine. This may allow earlier discharge of patients from the
      recovery room.

PMID- 10960385
TI  - A preliminary investigation of remifentanil as a labor analgesic.
AB  - IMPLICATIONS: In this preliminary investigation, we evaluated the safety and
      analgesic efficacy of IV remifentanil for labor pain. Four women were studied,
      and then the trial was terminated because administration of this novel synthetic
      opioid produced significant maternal side effects in the absence of effective
      pain control.

PMID- 10960386
TI  - Cortical blindness in a preeclamptic patient after a cesarean delivery
      complicated by hypotension.
AB  - IMPLICATIONS: Visual strokes can occur after prolonged hypotension or as a
      complication of preeclampsia-eclampsia. This case describes the diagnostic
      dilemma posed by a patient who developed transient blindness after a hypotensive
      episode during cesarean delivery for severe preeclampsia-eclampsia.

PMID- 10960388
TI  - Enterprise-wide patient scheduling information systems to coordinate surgical
      clinic and operating room scheduling can impair operating room efficiency.

PMID- 10960387
TI  - Arterial blood pressure and heart rate discrepancies between handwritten and
      computerized anesthesia records.
AB  - Previous publications suggest that handwritten anesthesia records are less
      accurate when compared with computer-generated records, but these studies were
      limited by small sample size, unblinded study design, and unpaired statistical
      comparisons. Eighty-one pairs of handwritten and computer-generated neurosurgical
      anesthesia records were retrospectively compared by using a matched sample
      design. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and
      heart rate (HR) data for each 5-min interval were transcribed from handwritten
      records. In computerized records, the median of up to 20 values was calculated
      for SAP, DAP, and HR for each consecutive 5-min epoch. The peak, trough, standard
      deviation, median, and absolute value of the fractional rate of change between
      adjacent 5-min epochs were calculated for each case. Pairwise comparisons were
      performed by using Wilcoxon tests. For SAP, DAP, and HR, the handwritten record
      peak, standard deviation, and fractional rate of change were less than, and the
      trough and median were larger than, those in corresponding computer records (all
      with P: < 0.05, except DAP median and HR peak). Considering together all the
      recorded measurements from all cases, extreme values were recorded more
      frequently in computerized records than in the handwritten records. IMPLICATIONS:
      The discrepancies between handwritten and computerized anesthesia records suggest
      that some of the data in handwritten records are inaccurate. The potential for
      inaccuracy should be considered when handwritten records are used as source
      material for research, quality assurance, and medicolegal purposes.

PMID- 10960389
TI  - Vasopressin improves survival after cardiac arrest in hypovolemic shock.
AB  - Survival after hypovolemic shock and cardiac arrest is dismal with current
      therapies. We evaluated the potential benefits of vasopressin versus large-dose
      epinephrine in hemorrhagic shock and cardiac arrest on vital organ perfusion, and
      the likelihood of resuscitation. In 18 pigs, 35% of the estimated blood volume
      was withdrawn over 15 min and ventricular fibrillation was induced 5 min later.
      After 4 min of cardiac arrest and 4 min of standard cardiopulmonary
      resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 7), 0.8
      unit/kg vasopressin (n = 7), or saline placebo (n = 4) was administered in a
      blinded, randomized manner. Defibrillation was attempted 2.5 min after drug
      administration, and all animals were subsequently observed for 1 h without
      further intervention. Spontaneous circulation was restored in 7 of 7 vasopressin
      animals, in 6 of 7 epinephrine pigs, and in 0 of 4 placebo swine. At 5 and 30 min
      after return of spontaneous circulation, median (minimum and maximum) renal blood
      flow after epinephrine was 2 (0-31), and 2 (0-48) mL. 100 g(-1). min(-1),
      respectively; and after vasopressin 96 (12-161), and 44 (16-105) mL. 100 g(-1).
      min(-1), respectively (P: <.01 between groups). Epinephrine animals developed a
      profound metabolic acidosis by 15 min after return of spontaneous circulation
      (mean arterial pH, 7.11 +/- 0.01), and by 60 min all epinephrine-treated animals
      had died. The vasopressin pigs had (P: = 0.015) less acidosis (pH = 7.26+/-0. 04)
      at corresponding time points, and all survived > or =55 min (P: < 0. 01). In
      conclusion, treatment of hypovolemic cardiac arrest with vasopressin, but not
      with large-dose epinephrine or saline placebo, resulted in sustained vital organ
      perfusion, less metabolic acidosis, and prolonged survival. Based on these
      findings, clinical evaluation of vasopressin during hypovolemic cardiac arrest
      may be warranted. IMPLICATIONS: The chances of surviving cardiac arrest in
      hemorrhagic shock are considered dismal without adequate fluid replacement.
      However, treatment of hypovolemic cardiac arrest with vasopressin, but not with
      large-dose epinephrine or saline placebo, resulted in sustained vital organ
      perfusion and prolonged survival in an animal model of suspended infusion
      therapy.

PMID- 10960390
TI  - The laryngeal mask for percutaneous endoscopic gastrostomy.
AB  - IMPLICATIONS: We report the successful use of the laryngeal mask airway for
      percutaneous endoscopic gastrostomy in an adult patient with a known difficult
      airway and severe cerebral palsy.

PMID- 10960391
TI  - Isoflurane increases brain oxygen reactivity in dogs.
AB  - We tested the possibility that large-dose isoflurane will produce a loss of brain
      tissue oxygen regulation in dogs. A total of 12 dogs were anesthetized with
      isoflurane, a craniotomy was performed, and a probe was inserted to measure brain
      tissue oxygen pressure (PtO(2)), carbon dioxide, and pH. Baseline measures were
      made during 1.5% end-tidal isoflurane with 30% oxygen ventilation, followed by
      95% oxygen ventilation. Six dogs (Group 1) were treated with 3% isoflurane and
      30% oxygen, followed by a second oxygen challenge with 95% O(2). Six dogs (Group
      2) received propofol to produce a similar suppression of the electroencephalogram
      as in Group 1, followed by 95% oxygen ventilation. Brain tissue oxygen reactivity
      was calculated by the increase in PtO(2) divided by the increase in arterial
      PO(2). During 1.5% isoflurane and propofol anesthesia, PtO(2) increased from 42
      to 62 mm Hg with oxygen ventilation, and brain tissue oxygen reactivity was 0.14%
      per mm Hg(-1). Brain tissue oxygen reactivity did not change during propofol
      anesthesia. With 3% isoflurane, PtO(2) increased from 52 to 113 mm Hg and brain
      tissue oxygen reactivity was 0.36% per mm Hg(-1) (P: < 0.05). These results
      suggest that the cerebrovasodilator and vasoplegic effects of large-dose
      isoflurane attenuate brain oxygen regulation. IMPLICATIONS: We evaluated the
      ability of oxygen ventilation to increase brain tissue oxygen pressure in dogs
      anesthetized with 1.5% and 3% isoflurane and propofol. Increases in tissue oxygen
      were significantly greater during 3% isoflurane compared with 1.5% isoflurane and
      propofol.

PMID- 10960392
TI  - The effects of nicardipine on dynamic cerebral autoregulation in patients
      anesthetized with propofol and fentanyl.
AB  - We investigated the effects of nicardipine on dynamic cerebral pressure
      autoregulation in 13 normal adult patients undergoing gynecologic or orthopedic
      surgery. Anesthesia was induced and maintained with propofol and fentanyl.
      Hypotension to a mean arterial pressure of 60-65 mm Hg was induced and maintained
      with a continuous infusion of nicardipine. Time-averaged mean blood flow velocity
      in the right middle cerebral artery was measured continuously by using
      transcranial Doppler ultrasonography. The cerebral autoregulatory responses were
      activated by releasing thigh cuffs. The actual blood flow velocity in the right
      middle cerebral artery response to acute change in mean arterial pressure was
      fitted to 1 of 10 computer-generated curves to determine the dynamic rate of
      cerebral autoregulation (dRoR), and the best fitting curve was used. The
      autoregulation test was repeated until two values of dRoR were obtained at
      baseline and during induced hypotension. Nicardipine significantly reduced dRoR
      values of 13.1% +/- 3.6%/s at baseline to 8.3% +/- 2.6%/s during hypotension (P:
      < 0.01). During deliberate hypotension induced by nicardipine, the cerebral
      dynamic autoregulatory response is impaired in normal adult patients.
      IMPLICATIONS: During deliberate hypotension induced by nicardipine, the cerebral
      dynamic autoregulatory response is impaired in normal adult patients.

PMID- 10960395
TI  - Aging reduces the efficacy of the simulated epidural test dose in anesthetized
      adults.
AB  - Aging is associated with reduced beta-adrenergic responsiveness. However, the age
      related effects on hemodynamic changes and effectiveness of a simulated epidural
      IV test dose have not been defined during general anesthesia. We studied 20 (140
      total) consecutive patients (ASA physical status I) assigned in each of the
      following age groups after endotracheal intubation and during stable end-tidal
      sevoflurane 2% and 67% nitrous oxide anesthesia (in yr): 10s, 20s, 30s, 40s, 50s,
      60s, and 70s. Each group first received normal saline 3 mL IV, followed 4 min
      later by 1.5% lidocaine 3 mL plus 15 microg epinephrine (1:200,000) IV for 5 s.
      Heart rate (HR) and systolic blood pressure (SBP) were continuously monitored for
      4 min after saline administration and the test dose injections. None receiving IV
      saline and all patients receiving IV test dose in age groups 10s to 50s developed
      HR increases > or = 10 bpm, whereas 17 and 13 patients met this HR criterion in
      age groups 60s and 70s (85% and 65% sensitivities), respectively. There was a
      significant inverse correlation between the maximum HR increase and the age (P: <
      0.001 by Spearman's rank correlation). However, none receiving saline and all
      patients receiving IV test dose in all age groups developed SBP increases of 15
      mm Hg, resulting in 100% efficacy based on the SBP criterion. We conclude that
      during stable sevoflurane anesthesia administration (a) the efficacy based on the
      HR criterion for detecting accidental intravascular injection of the epidural
      test dose is age-dependent, (b) the HR criterion may be clinically applicable
      only in patients <60 yr of age, and (c) the SBP criterion is effective for all
      age groups studied. IMPLICATIONS: To determine whether an epidurally administered
      local anesthetic has been unintentionally injected into a blood vessel, a small
      dose of epinephrine is often added to a local anesthetic. We found that an
      increase in systolic blood pressure > or = 15 mm Hg is a more useful indicator
      than an increase in heart rate > or = 10 bpm in the patients > or = 60 yr old
      during stable sevoflurane anesthesia administration.

PMID- 10960393
TI  - Multiple-injection axillary brachial plexus block: A comparison of two methods of
      nerve localization-nerve stimulation versus paresthesia.
AB  - We conducted this prospective study to compare the onset time and the success
      rate of a multiple-injection axillary brachial plexus block performed by using
      two methods of nerve localization: paresthesia elicitation or nerve stimulation.
      Each of the major nerves of the plexus was located by elicitation of a
      paresthesia (Group PAR; n = 50) or by nerve stimulation (Group PNS; n = 50) and
      injected with 10 mL of local anesthetic solution. Time to perform the block,
      onset time of the primary block, time to achieve readiness for surgery, and total
      anesthetic time were significantly shorter in Group PNS than in Group PAR. The
      incidence of complete block was larger in Group PNS than in Group PAR (91% vs
      76%; P: < 0. 05), and this was related to a larger success rate for anesthetizing
      the radial and the musculocutaneous nerves (P: < 0.05). The frequency of venous
      puncture was larger in Group PAR (P: < 0.05). For multiple-injection axillary
      brachial plexus block, we conclude that nerve stimulation resulted in a greater
      success rate and a faster onset than paresthesia elicitation, and it should be
      considered when the radial and musculocutaneous nerve distributions are involved
      in the surgical area. IMPLICATIONS: Two methods of nerve localization were
      compared when performing an axillary brachial plexus block by the multiple
      injection technique. Nerve stimulation provided a faster onset and a greater
      incidence of complete block, related to a better success rate for anesthetizing
      the radial and the musculocutaneous nerves, than paresthesia elicitation.

PMID- 10960396
TI  - Temperature monitoring and management during neuraxial anesthesia: an
      observational study.
AB  - Temperature monitoring and thermal management are rare during spinal or epidural
      anesthesia because clinicians apparently restrict monitoring to patients with an
      expected risk of hypothermia. This implies that anesthesiologists can predict
      patient thermal status without monitoring core temperature. We therefore, tested
      the hypotheses that during neuraxial anesthesia: 1) amount of core hypothermia
      depends on the magnitude and duration of surgery; 2) temperature monitoring and
      thermal management are used selectively in patients at high risk of hypothermia;
      and 3) anesthesiologists can estimate patient thermal status. We evaluated
      thermal status on arrival in the recovery room along with intraoperative thermal
      management and monitoring in 120 patients. Anesthesiologists were asked if their
      patients were hypothermic (<36 degrees C). There was no correlation between the
      magnitude or duration of surgery and initial postoperative core temperature in
      unwarmed patients. Temperature monitoring and thermal management were not used
      selectively in high-risk patients. Initial postoperative tympanic membrane
      temperatures were <36 degrees C in 77% of patients and <35 degrees C in 22%. Body
      temperature was monitored intraoperatively in 27% of the patients and forced-air
      warming was used in 31%. Anesthesiologists failed to accurately estimate whether
      their patients were hypothermic. Our results suggest that temperature monitoring
      and management during neuraxial anesthesia is currently inadequate. IMPLICATIONS:
      In this observational study, we evaluated core temperatures and intraoperative
      thermal management in patients undergoing spinal or epidural anesthesia.
      Hypothermia was common, however, rarely detected either by temperature monitoring
      or estimates by anesthesiologists. In addition, it was not treated with active
      warming. Consequently, temperature monitoring and management have to be done
      during neuraxial anesthesia.

PMID- 10960394
TI  - The effects of epidural bupivacaine, morphine, and their combination on thermal
      nociception with different stimulus intensity in rats.
AB  - The analgesic effect of drugs depends on the stimulus intensity as well as the
      potency of the drugs. We investigated the effects of stimulus intensity on
      antinociceptive potencies of epidural bupivacaine + morphine. Sprague-Dawley rats
      implanted with chronic lumbar epidural catheters were tested for paw withdrawal
      response to thermal stimulation after the epidural injection of bupivacaine,
      morphine, or bupivacaine + morphine. Two stimulation currents were used, 5.1 and
      4.6 A, to provide baseline response latency of approximately 5.0 s (high
      intensity) and 10.0 s (low intensity), respectively. Increasing the dose of
      epidural morphine in a dose range that had a maximum effect on low-intensity
      stimulation was not effective for high-intensity stimulation. Bupivacaine, which
      alone had no effect, potentiated the antinociceptive effect of epidural morphine
      at both high- and low-intensity stimuli similarly. We concluded that bupivacaine
      potentiated the analgesic effect of epidural morphine at both weak and strong
      nociceptive stimuli similarly, whereas increasing the dose of epidural morphine
      was not as effective for strong nociceptive stimulation. Therefore, adding
      bupivacaine might be more effective than increasing the dose of epidural morphine
      for intense nociception. IMPLICATIONS: When patients have severe pain even when
      receiving epidural morphine, adding bupivacaine might be more effective than
      increasing the dose of epidural morphine.

PMID- 10960397
TI  - An assessment of the value of intraperitoneal meperidine for analgesia
      postlaparoscopic tubal ligation.
AB  - Patients undergoing laparoscopic procedures may experience postoperative pain.
      The intraperitoneal (IP) administration of drugs is controversial but has proven
      effective in some studies for the relief of postoperative pain. However, some
      investigators have not been able to confirm the analgesic efficacy of IP local
      anesthetics. The administration of IP opioids for the relief of postoperative
      pain has received little attention. At the end of laparoscopic tubal ligation,
      100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP
      and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured
      at rest and with movement. Pain scores were significantly lower in the group
      receiving the IP meperidine both at rest (P: < 0.01) and with movement (P: <
      0.05). We conclude that the combination of intraperitoneal bupivacaine and
      intraperitoneal meperidine was better than the combination of IP bupivacaine and
      IM meperidine for postoperative analgesia in patients undergoing laparoscopic
      tubal ligation. IMPLICATIONS: The combination of bupivacaine and meperidine
      delivered to the intraperitoneal cavity proved superior to equivalent doses of
      intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in
      patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of
      analgesia proved effective in this study and merits further study and more
      widespread use.

PMID- 10960398
TI  - Tolerability of large-dose intravenous levobupivacaine in sheep.
AB  - In preclinical pharmacological studies of levobupivacaine (S-bupivacaine), we
      determined its tolerability, cardiovascular actions, and pharmacokinetics, and we
      estimated its margin of safety compared with bupivacaine in conscious sheep.
      Levobupivacaine HCl. H(2)O was infused IV for 3 min into 10 previously
      instrumented ewes (approximately 50 kg). On subsequent days, the doses were
      increased by 50 mg from 200 or 250 mg until fatality occurred. All doses produced
      convulsions, QRS widening, and cardiac arrhythmias. With incremental doses, 4 of
      4 animals survived 200 mg, 7 of 10 survived 250 mg, 3 of 7 survived 300 mg, but 0
      of 3 survived 350 mg. Death resulted from sudden onset ventricular fibrillation
      (n = 3, within 2-3 min), electromechanical dissociation-pump failure (n = 5,
      within 4-5 min), or ventricular tachycardia-induced cardiac insufficiency (n = 2,
      >10 min). The estimated fatal dose (mean +/- SD) was 277 +/- 51 mg for
      levobupivacaine (compared with 156 +/- 31 mg found previously for bupivacaine).
      Pharmacokinetic analysis indicated initial and total distribution volumes = 4.5
      (+/-1.6) and 97 (+/-22) L, total clearance = 1.7 (+/-0.4) L/min, and slow half
      life = 70 (+/-29) min; these values did not differ from those found previously
      with smaller doses. Heart and brain tissue levobupivacaine concentrations were
      approximately 3 times those in arterial blood. The doses of levobupivacaine
      survived were larger than found previously for bupivacaine, indicating its
      greater margin of safety. IMPLICATIONS: Levobupivacaine produced fatal cardiac
      toxicity at doses significantly greater than those found in previous studies with
      bupivacaine. As the two drugs have similar potency for producing clinical nerve
      blocks, the data imply that levobupivacaine should provide a safer alternative to
      bupivacaine in practice.

PMID- 10960399
TI  - Gabapentin in pain management.

PMID- 10960401
TI  - Downbeat nystagmus associated with intravenous patient-controlled administration
      of morphine.
AB  - IMPLICATIONS: This case documents a patient who developed dizziness with
      downbeating nystagmus while receiving a relatively large dose of IV patient
      controlled analgesia morphine. Although there have been case reports of epidural
      morphine with these symptoms and signs, this has not been previously documented
      with IV or patient-controlled analgesia morphine.

PMID- 10960402
TI  - Microbiological, microstructure, and material science examinations of reprocessed
      Combitubes after multiple reuse.
AB  - Reprocessing (repeated cleaning, disinfection, and sterilization) and reuse of
      single-use medical devices has been performed safely with some devices. The aim
      of our study was to analyze whether reprocessing of the Combitubes (Kendall
      Sheridan, Argyll, NY) airway device, used for emergency endotracheal intubation
      and difficult airway management, is possible and can be performed appropriately
      and safely. Microbiological, microstructure, and material science examinations
      were performed with unused, as well as multiple reused and reprocessed
      Combitubes. The reprocessing procedure consisted of a cleaning, a disinfection, a
      final inspection, and a sterilization. Microbiological examinations of multiple
      reused and reprocessed Combitubes found no test organisms in quantitative
      cultures. A microbial reduction between four and five log levels compared with
      nonreprocessed tubes was found. Microstructure analysis for the examination of
      topographical alterations and changes in the chemical composition of the surface
      demonstrated nonsignificant alterations between new and reprocessed medical
      devices. In material science examinations, cuff burst pressures were not
      different between unused and multiple reprocessed Combitubes. The results of all
      examinations proved that the decontamination process is adequately effective, and
      that no significant superficial alterations are generated by the multiple reuse
      and reprocessing of the Combitubes. To assure uniformly good results, a quality
      management system must be established and only validated methods should be used.
      IMPLICATIONS: Reprocessing of single-use medical devices offers the opportunity
      of significant savings and is already performed with some devices.
      Microbiological, microstructure, and material science examinations proved that
      reprocessing of multiple reused Combitubes (Kendall-Sheridan, Argyll, NY), mainly
      used for emergency airway management, is possible and safe.

PMID- 10960403
TI  - Thermosoftening treatment of the nasotracheal tube before intubation can reduce
      epistaxis and nasal damage.
AB  - We evaluated whether a thermosoftening treatment with warm saline of a
      nasotracheal preformed tube can improve navigability through the nasal
      passageways and reduce epistaxis and nasal damage. A total of 150 patients were
      randomly allocated to three groups: Group I (untreated tube group, n = 50), Group
      II (35 degrees C treated tube group, n = 50), and Group III (45 degrees C treated
      tube group, n = 50). In Groups II and III, the tubes were softened at 35 +/- 2
      degrees C and 45 +/- 2 degrees C with warm saline, respectively. In Group I the
      tube was prepared at room temperature (25 +/- 2 degrees C). The incidence of
      epistaxis and nasal damage in Groups II and III was significantly less than that
      of Group I (P: < 0.05). Despite the more frequent incidence of smooth passage in
      Group III, no statistical difference was found among the groups. Logistic
      regression analysis also confirmed that epistaxis was more likely to be reduced
      when the tube had been thermosoftened (odds ratio = 1.46, 95% confidence interval
      = 1.02, 2.11). We conclude that simple thermosoftening treatment of the
      nasotracheal tube with warm saline helps to reduce epistaxis and nasal damage.
      IMPLICATIONS: Thermosoftening treatment of a nasotracheal tube with warm saline
      before intubation can effectively reduce epistaxis and nasal damage. This
      technique is safe, easy, and suitable for all types of tubes and does not require
      additional implements.

PMID- 10960400
TI  - Recurring brachial plexus neuropathy in a diabetic patient after shoulder surgery
      and continuous interscalene block.
AB  - IMPLICATIONS: The performance of regional blockade on a patient with a
      preexisting neurologic condition or a history of neurologic complications after
      regional anesthesia is controversial. We present a case of recurring brachial
      plexus neuropathy in a diabetic patient after two shoulder procedures performed 4
      mo apart. In both cases, the patient underwent intensive physical therapy with
      continuous postoperative interscalene analgesia.

PMID- 10960405
TI  - The effect on intracuff pressure of various nitrous oxide concentrations used for
      inflating an endotracheal tube cuff.
AB  - We sought to determine the optimal concentration of nitrous oxide (N(2)O) for
      inflating endotracheal tube cuffs, to avoid overinflation and air leaks. Female
      patients undergoing endotracheal intubation (inner diameter 7.5 mm) during
      anesthesia with 67% N(2)O were randomly assigned to five groups of 25 subjects
      each, in which cuffs were inflated with 0% (Air), 30% (N30), 40% (N40), 50%
      (N50), or 67% (N67) N(2)O. The cuff pressure and the N(2)O concentration in the
      cuff were measured. In an additional 15 patients (N40-a group), pilot balloons
      were replaced with metal tubes, and the mouths and noses of the patients were
      wrapped with tape, to minimize N(2)O efflux into the air. Postoperative sore
      throats were evaluated in double-blinded interviews. Cuff pressures increased
      significantly in the Air and N30 groups but decreased in the N67 group. Cuff
      pressures were <22 mm Hg in the N40 and N50 groups, but the N50 group had air
      leaks. The N(2)O concentration in the cuff in the N40 group was significantly
      smaller than that in the N40-a group, suggesting N(2)O rediffusion. The incidence
      of sore throats (40% in the Air group) was reduced significantly in the N40 and
      N50 groups. Therefore, 40% N(2)O is optimal for filling the cuff during
      anesthesia with 67% N(2)O. IMPLICATIONS: Nitrous oxide (N(2)O) diffuses into the
      cuff, equilibrating at a smaller concentration than the gas mixture with which
      patients are ventilated. Our data indicate that inflation of the cuff with 40%
      N(2)O is recommended to prevent both excessive endotracheal cuff pressure and air
      leaks during anesthesia with 67% N(2)O, reducing postoperative sore throats.

PMID- 10960404
TI  - The safety of one, or repeated, vital capacity maneuvers during general
      anesthesia.
AB  - A vital capacity maneuver (VCM) (inflating the lungs to 40 cm H(2)O for 15 s) is
      effective in relieving atelectasis during general anesthesia or after
      cardiopulmonary bypass (CPB). The study was undertaken to investigate the safety
      of one or repeated VCM. Five groups of six pigs were studied. Two groups had
      general anesthesia for 6 h and one group received a VCM every hour. Three other
      groups received CPB. VCM was performed after CPB in two of these groups. VCM was
      then repeated every hour in one of the groups. Lung damage was evaluated by
      extravascular lung water (EVLW) measurement, light microscopy, and the half-time
      (T(1/2)) of disappearance from the lung of a nebulized aerosol containing (99m)Tc
      DTPA. No changes were noted in extravascular lung water. The pigs subjected to
      VCM decreased their T(1/2). In the groups exposed to repeated VCM, T(1/2)
      remained lowered (CPB pigs) or decreased over time (non-CPB pigs). No lung damage
      could be seen on the morphology study. These results suggest that one VCM is a
      safe procedure. The increase in lung clearance of (99m)Tc-DTPA not associated
      with an increase in lung water when VCM is repeated may have been caused by an
      increase in lung volume. Therefore, repeated VCM also appears to be safe.
      IMPLICATIONS: This study demonstrates in an animal model that inflating the lung
      once or repeatedly to the vital capacity is a safe procedure. This maneuver, also
      called the vital capacity maneuver, can be used to relieve lung collapse which
      occurs in all patients during general anesthesia.

PMID- 10960406
TI  - Postoperative recovery after desflurane, propofol, or isoflurane anesthesia among
      morbidly obese patients: a prospective, randomized study.
AB  - Recovery from anesthesia might be compromised in obese patients. Because of its
      pharmacological properties, desflurane might allow rapid postoperative recovery
      for these patients. We compared postoperative recovery for 36 obese patients
      randomized to receive either desflurane, propofol, or isoflurane to maintain
      anesthesia during laparoscopic gastroplasties. Anesthesia was induced with
      propofol and succinylcholine IV and was maintained with rocuronium, alfentanil,
      inhaled nitrous oxide, and the study drug. Immediate recovery (i.e., times from
      the discontinuation of anesthesia to tracheal extubation, eye opening, and the
      ability to state one's name) was measured. At the time of postanesthesia care
      unit (PACU) admission, arterial saturation and the ability of patients to move
      were recorded. In the PACU, intermediate recovery was measured by using sedation
      and psychometric evaluations, 30, 60, and 120 min postoperatively. Data were
      compared between groups by using the Kruskal-Wallis and chi(2) tests. Results
      were reported as means +/- SD. P: < 0.05, compared with desflurane, was
      considered significant. Immediate recovery occurred faster, and was more
      consistent, after desflurane than after propofol or isoflurane (times to
      extubation were 6 +/- 1 min, 13 +/- 8 min [P: < 0.05, compared with desflurane],
      and 12 +/- 6 min [P: < 0.05, compared with desflurane], respectively). At PACU
      admission, SpO(2) values were significantly higher and patient mobility was
      significantly better after desflurane than after isoflurane or propofol. Sedation
      was significantly less pronounced with desflurane at 30 and 120 min
      postoperatively. In morbidly obese patients, postoperative immediate and
      intermediate recoveries are more rapid after desflurane than after propofol or
      isoflurane anesthesia. This advantage of desflurane persists at least for 2 h
      after surgery and is associated with both an improvement in patient mobility and
      a reduced incidence of postoperative desaturation. IMPLICATIONS: In morbidly
      obese patients, postoperative immediate and intermediate recoveries are more
      rapid and consistent after desflurane than after propofol or isoflurane
      anesthesia.

PMID- 10960407
TI  - Naturally occurring variability in anesthetic potency among inbred mouse strains.
AB  - We measured the naturally occurring variability in anesthetic potency, defined by
      the minimum alveolar anesthetic concentrations (MACs) of inhaled anesthetics
      required to produce immobility in response to noxious stimuli, in seven widely
      used laboratory mouse strains. To these data, we added similar data for eight
      other mouse strains. The average MAC values for each anesthetic for the 15
      strains were normally distributed, with a coefficient of variation (ratio of SD
      to mean) of 0.1. The range of MAC values was 39% for desflurane, 44% for
      isoflurane, and 55% for halothane. MAC values were highly reliable, with
      approximately 1% of the variance in MAC measurements for the strains being
      explained by measurement error. One hundred forty-six statistically significant
      differences among the 15 strains were found for the three inhaled anesthetics
      (isoflurane, desflurane, and halothane). Our results suggest that multiple genes
      underlie the observed variability in anesthetic potency. IMPLICATIONS: Laboratory
      mouse strains differ significantly in susceptibility to anesthetics. These
      phenotypic differences may be exploited to help determine the genetic basis of
      anesthetic-induced immobility.

PMID- 10960408
TI  - The hemodynamic and metabolic effects of tourniquet application during knee
      surgery.
AB  - We evaluated the effects of tourniquet application on the cardiovascular system
      and metabolism in 10 young men undergoing knee surgery with general anesthesia.
      The duration of inflation was from 75 to 108 min. Heart rate, mean arterial
      pressure, cardiac index (CI) by pulse contour method, and systemic vascular
      resistance were measured before, during, and after tourniquet inflation. pH,
      PaO(2), PaCO(2), and lactate blood concentrations were also measured. VO(2) and
      VCO(2) were assessed every minute from tracheal intubation up to 15 min after
      tourniquet deflation and VO(2) in excess of the basal value over the 15 min after
      deflation (VO(2)exc) was calculated. Mean arterial pressure increased 26% (P: <
      0.05) during inflation and returned to basal values after deflation. CI did not
      change immediately after inflation; although, thereafter, it increased 18% (P: <
      0.05). Five minutes after deflation, CI further increased to a value 40% higher
      than the basal value. Therefore, systemic vascular resistance increased 20%
      suddenly after inflation (P: < 0.05) and decreased 18% after deflation (P: <
      0.05). VO(2) and VCO(2) remained stable during inflation and increased (P: <
      0.05) after deflation. VO(2)exc depended on duration of tourniquet inflation time
      (Tisch) (P: < 0.05). After deflation, PaCO(2) and lactate increased (P: < 0.05)
      while Tisch increased. We conclude that tourniquet application induces
      modifications of the cardiovascular system and metabolism, which depend on
      tourniquet phase and on Tisch. Whether these modifications could be relevant in
      patients with poor physical conditions is not known. IMPLICATIONS: The clinical
      effects of tourniquet application were evaluated in 10 young men undergoing knee
      surgery. Our data indicate that tourniquet application causes hemodynamic and
      metabolic changes which may become clinically relevant after a long period of
      tourniquet inflation, particularly in patients with concomitant cardiovascular
      diseases.

PMID- 10960409
TI  - The mechanism of pancuronium potentiation of mivacurium block: use of the
      isolated-arm technique.
AB  - The neuromuscular blocking effects of mivacurium are greatly enhanced when
      mivacurium is preceded by a subparalyzing dose of pancuronium. The mechanism of
      this potentiation has not been elucidated. This study investigated the effects of
      the anticholinesterase activity of a small dose of pancuronium on the
      neuromuscular blocking effects of mivacurium. Forty patients were enrolled in the
      study. The neuromuscular effects of 7.5 and 15 microg/kg pancuronium, followed by
      50 and 100 microg/kg mivacurium, were assessed in Groups PM1 and PM2 (n = 20),
      respectively. The neuromuscular effects of 65 and 130 microg/kg mivacurium were
      assessed in Groups M1 and M2 (n = 20), respectively. One arm was excluded from
      circulation with a tourniquet, which was inflated before the injection of
      pancuronium and deflated 3 min after the injection of mivacurium. The plasma
      cholinesterase activity was measured before induction for all patients and 3 min
      after the injection of pancuronium for Groups PM1 and PM2. The plasma
      cholinesterase activity was decreased by 16% and 33% after pancuronium
      administration in Groups PM1 and PM2, respectively. In the nonexcluded arm,
      pancuronium significantly potentiated the effects of mivacurium. In the excluded
      arm, no significant block was detected for Groups M1 and M2, whereas the maximal
      degree of neuromuscular block was 79% and 100% for Groups PM1 and PM2,
      respectively. Using the isolated-arm technique, we suggest that pancuronium
      potentiation of the neuromuscular blocking effects of mivacurium is more likely
      attributable to an increase in the effective plasma concentration of mivacurium
      than to occupancy of postsynaptic acetylcholine receptors. IMPLICATIONS: Using
      the isolated-arm technique, we suggest that pancuronium potentiation of the
      neuromuscular blocking effects of mivacurium is more likely attributable to an
      increase in the effective plasma concentration of mivacurium than to occupancy of
      postsynaptic acetylcholine receptors.

PMID- 10960410
TI  - Protein binding and the metabolism of thiamylal enantiomers in vitro.
AB  - Thiamylal, a chiral thiobarbiturate, is marketed as a racemic product. We studied
      the serum protein binding and microsomal metabolism of thiamylal enantiomers in
      vitro. The unbound fraction of R(+)-thiamylal was greater than that of S(-)
      thiamylal. The analysis of binding data revealed that both enantiomers bound to
      human serum albumin through only one site. In displacement studies with site
      specific probes, dansylsarcosine, but not warfarin, significantly decreased the
      binding of both enantiomers. The bindings of enantiomers were also decreased by
      octanoate and a large concentration of oleate. These findings suggest that both
      enantiomers bind to Site II of albumin with higher affinity for S(-)-enantiomer.
      R(+)-thiamylal was metabolized more rapidly than S(-)-enantiomer by human liver
      microsomes. An experiment with isoform-selective inhibitors and cytochrome P-450
      (CYP) isoforms showed that CYP2C9 had the highest activity for the metabolism of
      both enantiomers, the activity being 7 to 10 times that of CYP2E1 and CYP3A4.
      CYP2C9 showed a significantly rapid metabolism of R(+)-enantiomer, suggesting
      that CYP2C9 is mainly involved in the enantioselective metabolism of thiamylal.
      IMPLICATIONS: Because clinically marketed thiamylal is a racemic compound, a
      pharmacokinetic study of each enantiomer may be beneficial. We found that the
      enantioselectivity of thiamylal existed in protein binding and metabolism. This
      may be caused by the differences in the affinities of enantiomers for albumin and
      cytochrome P-450 isoform.

PMID- 10960411
TI  - Nonstereoselective inhibition of neuronal nicotinic acetylcholine receptors by
      ketamine isomers.
AB  - We have found that racemic ketamine strongly inhibits the current mediated
      through neuronal nicotinic acetylcholine receptors (nAchRs) in PC12 cells, a rat
      pheochromocytoma cell line. Ketamine stereoisomers have different potencies for
      the anesthetic action, with the S-enantiomer being about 3 times as potent as the
      R-enantiomer. The purpose of this study was to clarify if the inhibitory effects
      of ketamine on neuronal nAchRs contribute to their anesthetic effect. We compared
      potencies of ketamine enantiomers for neuronal nAchR inhibition with those for
      the anesthetic action. S(+) and R(-) ketamine inhibited the nicotine-induced
      whole-cell current in a dose-dependent manner at the membrane potential of -60
      mV. They accelerated the current decay, resulting in the larger effects on the
      nondesensitized current than on the peak current. There was no significant
      difference in the concentrations for 50% inhibition between the stereoisomers.
      The ketamine isomers exerted the same effects on single-channel properties
      estimated from analysis of the nicotine-induced current noise. These results
      indicate that the inhibitory action of ketamine isomers on neuronal nAchRs is not
      stereoselective. Although our findings do not deny possible involvement of these
      receptors in ketamine anesthesia, they suggest that inhibition of neuronal nAchRs
      is not primarily responsible for the anesthetic action of this anesthetic.
      IMPLICATIONS: We found that inhibition of neuronal nicotinic acetylcholine
      receptors by ketamine is not stereoselective in PC12 cells. The result suggests
      that this effect does not directly correlate with the anesthetic action of
      ketamine.

PMID- 10960412
TI  - Hyperbaric nitrogen prolongs breath-holding time in humans.
AB  - Either an increase in PaCO(2) or a decrease in PaO(2), can affect respiratory
      stimulation through respiratory centers, thus influencing breath-holding time
      (BHT). This study was designed to determine whether and how hyperbaric air could
      influence BHT in comparison with hyperbaric oxygen in humans. We studied 36
      healthy volunteers in a multiplace hyperbaric chamber. BHT, pulse oximeter, and
      transcutaneous carbon dioxide tension were measured at 1 and 2.8 atmosphere
      absolute (ATA) in two groups. Group A (n = 20) breathed air. Group O (n = 16)
      breathed oxygen with a face mask (5 L/min). BHTs were 108 +/- 28 s at 1.0 ATA and
      230 +/- 71 s at 2.8 ATA in Group A, and 137 +/- 48 s at 1.0 ATA and 180 +/- 52 s
      at 2.8 ATA in Group O. Transcutaneous carbon dioxide tension in Group A (59 +/- 2
      mm Hg) was higher than that in Group O (54 +/- 2 mm Hg) at the end of maximal
      breath-holding at 2.8 ATA. The prolongation of BHT in hyperbaric air is
      significantly greater than that in hyperbaric oxygen. IMPLICATIONS: Breath
      holding time is significantly prolonged in hyperbaric air than it is in
      hyperbaric oxygen. The mechanism involves the anesthetic effect of nitrogen
      suppressing the suffocating feeling during breath-holding.

PMID- 10960413
TI  - The utility of three-dimensional computed tomography in unanticipated difficult
      endotracheal intubation.
AB  - IMPLICATIONS: We experienced a case of unanticipated difficult intubation with
      direct laryngoscopy because of narrowing of the retropharyngeal air space and
      laryngeal vestibulum. It is suggested that three-dimensional computed tomography
      is useful for evaluating both the abnormality of an airway and its relationship
      to surrounding tissue.

PMID- 10960416
TI  - Laureates of the History of Anesthesia, 2000.

PMID- 10960414
TI  - Depression of evoked electromyographic (EEMG) responses by propofol in a patient
      with human T-cell lymphotropic virus type I-associated myelopathy (HAM).
AB  - IMPLICATIONS: We report a patient with human T-cell lymphotropic virus type I
      associated myelopathy. Although muscle strength in both of the upper extremities
      was normal in this patient, evoked electromyogram of the adductor pollicis was
      depressed by propofol at the induction of anesthesia.

PMID- 10960415
TI  - General anesthesia in a patient on long-term amphetamine therapy: is there cause
      for concern?
AB  - IMPLICATIONS: Amphetamines are powerful, sympathomimetic amines that, when used
      chronically, can profoundly effect a patient's cardiovascular stability during
      anesthesia and surgery. Amphetamines are the third most widely abused class of
      drugs in the United States. They also have legitimate medical use for attention
      deficit disorder with hyperactivity, exogenous obesity, and narcolepsy. We report
      a case of a patient with a 40-yr history of chronic amphetamine use having
      undergone two general anesthesias without complication.

PMID- 10960417
TI  - Right versus left double-lumens for left-sided thoracic surgery.

PMID- 10960418
TI  - Right-sided double-lumen endobronchial tubes for left-sided thoracic surgery.

PMID- 10960419
TI  - The prophylactic antiemetic efficacy of naloxone during patient-controlled opioid
      analgesia.

PMID- 10960420
TI  - Meningitis after spinal anaesthesia.

PMID- 10960421
TI  - Digital pulp space infiltration of local anesthetic enhances pulse oximeter
      signal

PMID- 10960422
TI  - Nitroglycerin and uterine relaxation.

PMID- 10960423
TI  - Potency, impotency, and importance!

PMID- 10960424
TI  - Heparin-mediated hypotension associated with cardiac surgery.

PMID- 10960425
TI  - Complication after artery catheterization: digital gangrene in a patient with
      myeloproliferative disease with thrombocytosis.

PMID- 10960426
TI  - On the effect of propofol on human colonic muscle.

PMID- 10960427
TI  - Introduction

PMID- 10960428
TI  - Helicobacter pylori infection: a comparative review of existing management
      guidelines.
AB  - A central feature of general practice is the use of time in the management of
      patients and their illnesses. The use of active interventions such as
      investigations or therapies within the context of this dimension has implications
      for the development of clinical guidelines for primary care. Importantly, their
      recommendations of best practice must be compatible with the complexities of the
      holistic relationship between GP and patient. Many existing guidelines adopt a
      reductionist, algorithmic approach, losing applicability and relevance to primary
      care in the process. Here we identify the key features in the primary care
      management of the patient with dyspepsia, and examine the utility of existing
      guidelines for the management of Helicobacter pylori infection. Through this
      comparative analysis, the scope and nature of primary care-centred management
      guidelines are identified.

PMID- 10960429
TI  - The management of Helicobacter pylori infection in primary care: a systematic
      review of the literature.
AB  - OBJECTIVE: The aim of the present study was to provide evidence from the
      literature to inform the production of guidelines by the European Society for
      Primary Care Gastroenterology (ESPCG) for the management of Helicobacter pylori
      infection in primary care. METHODS: A systematic review was conducted, searching
      MEDLINE, EMBASE and the Cochrane Library. The systematic review was designed to
      answer a number of question: the role of H.pylori in the aetiology of peptic
      ulcer disease (PUD), gastric cancer (GC), non-ulcer dyspepsia (NUD) and
      oesophagitis; non-invasive testing for H.pylori and post-treatment testing;
      eradication therapy; and cost issues. Selection of records concentrated on the
      highest quality studies, i.e. systematic reviews, meta-analyses and cost
      analyses. RESULTS: Helicobacter pylori infection is a causal factor in PUD and GC
      but not in NUD or oesophagitis. Serological tests and urea breath tests (UBTs)
      can be used for the detection of H.pylori, but UBT is the preferred choice for
      post-treatment testing. Proton pump inhibitor (PPI)-based triple regimens are the
      preferred eradication therapy. Eradication therapy is more cost-effective than
      long-term maintenance therapy. CONCLUSIONS: Strong evidence is available for
      answering questions on the aetiology of stomach ulcers and GU, eradication
      therapies and cost issues. Weaker evidence is available for answering the
      questions on the aetiology of NUD and non-invasive testing. No evidence is
      available for answering the question on the role of H.pylori in the aetiology of
      oesophagitis.

PMID- 10960431
TI  - The use of consensus to develop guidelines for the management of Helicobacter
      pylori infection in primary care. European Society for Primary Care
      Gastroenterology.
AB  - BACKGROUND: Guidelines are an increasingly important feature of clinical practice
      and have proliferated over the past decade. When the evidence base for effective
      practice is limited, guidelines have to derive from the opinions and experience
      of those with knowledge of the subject. The manner in which a group synthesizes
      its individual opinions, the consensus process, is central to the validity and
      applicability of the resulting recommendations. This paper considers the
      theoretical issues in consensus development and describes the consensus process
      used in developing the European Society for Primary Care Gastroenterology
      guidelines for the management of Helicobacter pylori in primary care. METHODS: A
      consensus development conference of 48 GPs from nine European countries used case
      scenarios to define clinical management strategies in dyspepsia and H.pylori
      infection. Structured data collection from this meeting allowed a quantitative
      measure of the extent of consensus to be produced. RESULTS: Specific
      recommendations were produced for 15 decision points relevant to the management
      of H.pylori infection in primary care. DISCUSSION: Consensus development is often
      utilized in the production of guidelines for clinical practice. Guideline
      appraisal instruments fail to examine in depth the methods used for this
      important part of the development process. We describe an approach to consensus
      development which contains a simple measure of the strength of consensus
      underlying each recommendation.

PMID- 10960430
TI  - Tests for Helicobacter pylori infection: a critical appraisal from primary care.
AB  - BACKGROUND: Testing of patients for Helicobacter pylori infection is common in
      primary care settings. The accuracy of such tests has been assessed and critical
      appraisal of this literature can inform the clinical management of patients
      suspected of being infected with H. pylori METHODS: Literature evaluating the
      accuracy of diagnostic tests for H.pylori infection was sought as part of a
      systematic review of literature concerning the management of patients infected
      with H.pylori Studies were appraised and estimates of sensitivity and specificity
      were extracted. Positive and negative likelihood ratios (LRs) were calculated and
      the implications for post-test probabilities are reported. RESULTS: The
      sensitivity, specificity, LR+ and LR- for H.pylori infection tests ar:
      [(13)C]urea breath test (UBT), 96.5, 96, 24 and 0.04; [(14)C]UBT, 97.5, 95.5, 21
      and 0.03; serology, 91, 89.5, 8 and 0.11; near patient tests, 77, 74, 3 and 0.
      31; and meta-analysis of serology, 85, 79, 4 and 0.19. The range of pre-test
      probabilities of H.pylori infection in which the diagnostic tests were useful,
      estimated from primary studies, wer: [(13)C]UBT, 20-90%; [(14)C]UBT, 20-99%;
      serology, 30-80%; and near patient tests, 50-60%. CONCLUSIONS: Tests for H.pylori
      infection are useful in primary care when the pre-test probability of infection
      is neither too high nor too low. This indicates that the tests may not be useful
      for screening purposes but may help with differential diagnosis. Outside moderate
      pre-test probability ranges, the chances of a result being false is high, and
      such patients should either receive eradication without prior testing (if the
      probability of infection is sufficiently high) or the test result should be
      reconfirmed. When the pre-test probability falls below approximately 20%, a
      positive test result is unreliable. If the pre-test probability is above
      approximately 80%, a negative test result is unreliable. Clinical selection of
      patients needing testing should be used to limit testing to individuals with pre
      test probabilities within these ranges. The choice of diagnostic H.pylori test
      should be influenced by the H.pylori infection rate in the population being
      tested and the test characteristics. Recommendations for the use of tests,
      especially near patient tests, should be reconsidered. This critical appraisal
      supports the recommendations of the European Society for Primary Care
      Gastroenterology guidelines, arrived at by consensus, for testing for H.pylori
      infection in primary care.

PMID- 10960432
TI  - Guidelines on the management of H.pylori in primary care: development of an
      implementation strategy.
AB  - BACKGROUND: Clinical guideline programmes as being developed in many European
      countries contribute to quality of care in general practice. The applicability of
      multicountry guidelines will depend on country-specific circumstances.
      Implementation programmes are required for optimal compliance with guidelines.
      OBJECTIVE: In order to achieve optimal follow-up of the European Society for
      Primary Care Gastroenterology (ESPCG) Helicobacter pylori guidelines in general
      practice, we analysed factors that might obstruct compliance at national level,
      and integrated this in implementation programmes. METHOD: Discussion groups in
      eight participating countries reviewed epidemiological characteristics and
      diagnostic and therapeutic resources that would hinder applicability. The groups
      also indicated potential constraints to optimal compliance and developed a
      national implementation programme. RESULTS: Helicobacter pylori infection rates
      and peptic ulcer incidence vary widely across Europe, as do the availability,
      access and reimbursement of diagnostic test facilities for H.pylori Minor
      adaptation of the ESPCG guidelines is required in some countries. Implementation
      programmes have been developed and partially carried out in all countries.
      CONCLUSION: A pan-European approach to H.pylori guideline development should
      result in a framework of best practice into which nationally specific details can
      be incorporated, thus guaranteeing optimal follow-up of the guidelines and true
      improvement of dyspepsia management in primary care.

PMID- 10960433
TI  - The interaction between research and practice: a pan-European approach to
      managing H.pylori infection in primary care.
AB  - The transposition of evidence into clinical care presents many challenges. New
      knowledge may be immediately translatable to the practice setting, with barriers
      to be overcome before implementation. The early guidelines on Helicobacter pylori
      management presented an overview but were not able to take into account local
      factors and health care traditions, such as the non-availability of tests and
      established primary-secondary care relationships. Primary care is a specific
      specialty across most of Europe, existing within different health care systems
      and clinical traditions. The creation of H. pylori management guidelines, aimed
      at European primary care but adaptable to local national circumstances, presented
      a challenge in methodology and formulation. The process exposed similarities but
      also tensions between differing health care systems, as well as variations in the
      conditions in which GPs practise. Clinical differences, such as varying ulcer
      prevalence and drug resistance rates, highlighted the importance of guidelines
      being adaptable. This paper analyses the European Society for Primary Care
      Gastroenterology process of pan-European primary care agreement towards H.pylori
      management and how diverse views, traditions and national settings were
      reconciled through an evidence-based approach.

PMID- 10960434
TI  - Melatonin prevents pigment gallstone formation induced by bile duct ligation in
      guinea pigs.
AB  - Free radical-mediated oxidative stress has been implicated in the genesis of
      gallstone in vitro. This study was designed to examine the oxidative stress
      changes during pigment gallstone formation and to investigate whether melatonin
      (MLT) could act as a chemopreventive agent for cholelithiasis in a guinea pig
      model. The common bile duct of guinea pigs was ligated with or without MLT
      pretreatment. Animals were studied on day 7, 9, 12, and 14 after surgery. Stone
      and/or sludge developed in ligated guinea pigs without MLT. Fourier transform
      infrared spectra of the sludge showed the presence of calcium bilirubinate, whose
      peak height per milligram of sludge gradually increased with time after ligation.
      Total antioxidant activity (TAA) in bile of guinea pigs at day 14 after ligation
      reduced to one third of the level in sham-operated controls (P <.001). In
      addition, the bile of ligated guinea pigs had increased pH (P <.001), bile salts
      (P <.01), and malondialdehyde (MDA) (P <.05), compared to sham controls.
      Pretreatment of guinea pigs with MLT at a dose of 1,000 microg/kg significantly
      decreased the incidence of pigment gallstone formation at day 14 after ligation,
      as compared to no pretreatment (0/7 vs. 8/10). MLT also reverted the ligation
      induced changes in biliary bile salts, pH, MDA, and TAA to control levels. These
      in vivo findings support a causative role of oxidative stress in the bile duct
      ligation-induced pigment gallstone formation. Antioxidants may prove useful in
      preventing pigment gallstone formation in humans.

PMID- 10960435
TI  - Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation
      alone for the prevention of variceal rebleeding: a prospective, randomized trial.
AB  - Both beta-blockers and endoscopic variceal ligation (EVL) have proven to be
      valuable alternatives to sclerotherapy in the prevention of variceal rebleeding.
      Sucralfate is a mucosal protector. The effects of combinations of beta-blocker,
      band ligation, and sucralfate (triple therapy) remain unknown. A total of 122
      patients with a history of esophageal variceal bleeding were randomized to
      receive EVL only (group A, 62 patients) or triple therapy (group B, 60 patients).
      The procedure for the triple therapy included ligation with the addition of
      sucralfate granules until variceal obliteration. In addition, nadolol was
      administered during the course of the study or until death. After a median follow
      up of 21 months, recurrent upper gastrointestinal bleeding developed in 29
      patients (47%) in group A and 14 patients (23%) in group B (P =.005). Recurrent
      bleeding from esophagogastric varices occurred in 18 patients in group A and 7
      patients in group B (P =.001). Twenty-one patients in group A (50%) and 12
      patients (26%) in group B experienced variceal recurrence after variceal
      obliteration (P <.05). Treatment failure occurred in 11 patients (18%) in group A
      and in 4 patients (7%) in group B (P =.05). Twenty patients from group A and 10
      patients from group B died (P =.08); 9 and 4 of these deaths, respectively, were
      attributed to variceal hemorrhage (P =.26). The combination of ligation, nadolol,
      and sucralfate (triple therapy) proved more effective than banding ligation alone
      in terms of prevention of variceal recurrence and upper gastrointestinal
      rebleeding as well as variceal rebleeding.

PMID- 10960436
TI  - Recent portal or mesenteric venous thrombosis: increased recognition and frequent
      recanalization on anticoagulant therapy.
AB  - Characteristics and outcomes of recent portal or mesenteric venous thrombosis are
      ill-known. We intended to compare these features with those of patients with
      portal cavernoma, and also to assess the incidence of recanalization of recent
      thrombosis on anticoagulation therapy. All patients seen between 1983 and 1999
      were enrolled into this retrospective study if recent portal or mesenteric venous
      thrombosis or portal cavernoma had been documented, and if cancer of the liver,
      pancreas, or bile duct, intrahepatic block including cirrhosis, and obstruction
      of the hepatic veins had been ruled out. The proportion of recent thrombosis was
      7% in patients seen before 1990 and 56% after 1994 (P <.05). Patients with recent
      thrombosis (n = 33) or cavernoma (n = 108) did not differ with regard to age, sex
      ratio, or prevalence of prothrombotic states and of previous thrombotic events.
      In patients with recent thrombosis, septic pylephlebitis was more common and the
      incidence of gastrointestinal bleeding was lower (2.4 vs. 12.7/100 patient
      years). Recanalization occurred in 25 of 27 patients given anticoagulation and 0
      of 2 patients not given anticoagulation. The probability of recanalization was
      related to the extent of thrombosis (P =.003). In conclusion, mesenteric or
      portal venous thrombosis is increasingly recognized at an early stage. The
      features differentiating recent thrombosis and cavernoma are related to silent
      onset precluding early recognition and therapy in the latter. Frequent
      association with prothrombotic states and frequent recanalization on
      anticoagulation support the recommendation of early anticoagulation therapy in
      all patients with recent portal vein thrombosis.

PMID- 10960437
TI  - Multicenter randomized controlled trial of terlipressin versus sclerotherapy in
      the treatment of acute variceal bleeding: the TEST study.
AB  - Failure to control bleeding and early rebleeding account for the high mortality
      associated with variceal hemorrhage in cirrhosis. We compared endoscopic
      sclerotherapy to terlipressin, a drug that effectively controls acute bleeding
      while reducing in-hospital mortality. This multicenter randomized controlled
      trial included 219 cirrhotic patients admitted for endoscopy-proven acute
      variceal bleeding and randomized to receive repeated injections of terlipressin
      during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined
      as obtaining control of bleeding (24-hour bleeding-free period during the first
      48 hours) and lack of early rebleeding (any further bleeding from initial control
      to 5 days later) and survival during the study. Both groups were similar at
      inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not
      significant [NS]). Early rebleeding was responsible for 43% and 44% of failures,
      respectively. This high efficacy was observed in both Child-Pugh class A + B and
      Child-Pugh class C patients. Both treatments were similar regarding transfusion
      requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side
      effects appeared in 20% of patients receiving terlipressin and in 30% of those on
      sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In
      conclusion, terlipressin and sclerotherapy are equally highly effective therapies
      achieving the initial control of variceal bleeding and preventing early
      rebleeding. Both treatments are safe, but terlipressin is better tolerated.
      Therefore, terlipressin may represent a first-line treatment in acute variceal
      bleeding until the administration of elective therapy, especially in hospitals
      where a skilled endoscopist is not available 24 hours a day.

PMID- 10960438
TI  - Practices of liver biopsy in France: results of a prospective nationwide survey.
      For the Group of Epidemiology of the French Association for the Study of the
      Liver (AFEF).
AB  - A nationwide prospective study was conducted in France in 89 university and
      primary referral hospitals' liver units to evaluate practices of liver biopsy and
      the occurrence of complications. A total of 2,084 biopsies were analyzed,
      recording the indication, hemostasis parameters, experience of operator, route of
      biopsy, use of ultrasonography (US), type of hospitalization, side effects, and
      complications. Pain, anxiety, and discomfort were evaluated by patients by visual
      analogue scale (VAS). Biopsies were performed by experienced physicians (>150
      procedures performed) in 72%, and hepato-gastroenterologists in 89% of the cases.
      Hepatitis C was the indication in 54%. Sedation or premedication (atropine) was
      given in 46%. US-guidance was used in 56% of the cases. A day-care procedure was
      used in 27%. No deaths occurred, but severe complications were observed in 0.57%
      and increased with the number of passes and decreased with experience of
      operator, use of atropine, and US-guidance. Pain was independently related to
      general anesthesia, experience of the operator, female sex, and hepatitis C.
      Anxiety was increased in women. Discomfort was increased by venous access and
      decreased with an experienced operator. Acceptance of additional biopsies was
      related to a day-care procedure and independently related to general anesthesia
      and multiples passes. This study showed that (1) liver biopsy procedures vary
      greatly in France, (2) hepatitis C is the main indication for liver biopsy at
      present, (3) US-guidance should be developed to reduce severe complications, and
      (4) day-care procedures increase acceptance of a future biopsy and should also be
      used more often.

PMID- 10960439
TI  - Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular
      carcinoma cell lines.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in
      various transformed cell lines but not in almost-normal tissues. It is regulated
      by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, and 2 decoy
      receptors, TRAIL-R3 and TRAIL-R4. We investigated the expression of TRAIL-R- and
      TRAIL-induced apoptosis in human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2,
      and -R4 were expressed in 6 HCC cell lines examined, but TRAIL-R3 was expressed
      in only 2 of the 6 cell lines. In addition, immunohistochemical results revealed
      a high and prevalent expression of TRAIL-R1 and -R2 in human HCC tissues. Despite
      the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to
      TRAIL-induced apoptosis with no relation to nuclear factor kappa B (NF-kappaB)
      levels induced by TRAIL. TRAIL-induced death signal was inhibited with both
      decreased caspase-8 and caspase-3 activity. However, TRAIL induced significant
      apoptosis in the presence of a subtoxic level of actinomycin D, indicating that
      the TRAIL-induced apoptotic pathway is in place in these cell lines. In addition,
      we found that treatment with conventional chemotherapeutic agents, doxorubicin
      and camptothecin, dramatically augmented TRAIL-induced cytotoxicity in most of
      the HCC cell lines. Actinomycin D and camptothecin almost completely suppressed
      NF-kappaB induction by TRAIL, whereas doxorubicin had little effect. These
      results indicate that TRAIL, in combination with chemotherapeutic agents, may
      have therapeutic potential in the treatment of human HCC.

PMID- 10960441
TI  - Hepatocarcinogenesis in female mice with mosaic expression of connexin32.
AB  - Mice deficient for connexin32 (Cx32), the major gap junction forming protein in
      liver, are highly susceptible to hepatocarcinogenesis. Because the Cx32 gene is
      located on the X-chromosome, heterozygous females show mosaicism with respect to
      Cx32 expression; this enables their use in studying the effect of Cx32-deficiency
      in a mixed Cx32-plus/Cx32-minus environment in vivo. Female C3H/He mice
      (Cx32(+/+)) were crossed with Cx32-deficient C57BL/129Sv males (Cx32(Y/-)) to
      yield F1 females heterozygous with respect to Cx32 (Cx32(+/-)). Patches of
      hepatocytes were observed in normal liver that either expressed Cx32 or failed to
      express the protein. The mean fraction of Cx32-negative tissue in liver was about
      60% and did not change significantly with age of mice. Neoplastic liver lesions,
      induced in weanling mice, were identified in serial liver sections by their
      deficiency in glucose-6-phosphatase staining. Parallel sections were used for
      immunohistochemical demonstration of Cx32 protein. Smaller lesions were either
      homogenously Cx32-negative or showed unchanged to slightly elevated levels of
      Cx32 protein. There were no major differences in number and size distribution
      between lesions of these 2 phenotypes. In addition, larger lesions were mostly
      Cx32-negative but often contained embedded patches of Cx32-positive cells.
      Staining for the proliferation-associated nuclear antigen Ki-67 did not reveal
      significant differences between Cx32-negative and Cx32-positive hepatocytes in
      Cx32-mosaic tumors. This suggests that expression of Cx32 within a subpopulation
      of tumor cells does not negatively regulate their growth nor does it seem to
      affect the proliferation of their directly neighboring Cx32-negative
      counterparts.

PMID- 10960440
TI  - The impact of interferon gamma receptor expression on the mechanism of escape
      from host immune surveillance in hepatocellular carcinoma.
AB  - Interferon gamma (IFN-gamma) plays an important role in host defense mechanism
      and participates in the progression of chronic liver disease. IFN-gamma exerts
      its pleiotrophic effects by transcriptional regulation of expression of numerous
      genes, such as major histocompatibility complex (MHC) class I and Fas, through
      interaction with IFN-gamma receptor (IFN-gamma-R). Although hepatocytes in normal
      liver express weak or no IFN-gamma-R, those in acute and chronic liver disease up
      regulate its expression. A study using IFN-gamma-R alpha-chain knock-out mice
      revealed the actions of IFN-gamma on tumor cells as an extrinsic tumor-suppressor
      mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC)
      blocks the signal transduction of IFN-gamma to evade host immune surveillance. We
      examined the expression of IFN-gamma-R and IFN-gamma-inducible genes in 44 cases
      with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR)
      and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-gamma-R
      expression on the cell surface was up-regulated in 27 cases. In IFN-gamma-R
      negative cases (n = 15), tumor size was larger (P =.032), serum alpha-fetoprotein
      (AFP) level was higher (P =.001), intrahepatic and extrahepatic metastasis was
      more common (P =.044 and.013, respectively), and Ki-67 labeling index (LI) was
      higher (P =.041), compared with IFN-gamma-R-positive cases. Accordingly, the
      evasion mechanism may play an important role in progression, especially
      metastasis, in HCC. The significant correlation between the status of IFN-gamma-R
      and the expression of Fas and MHC implies that the loss of IFN-gamma-R might
      contribute to the mechanism of escape from host immune rejection in HCC.

PMID- 10960443
TI  - Hyperstimulation with interleukin 6 inhibits cell cycle progression after
      hepatectomy in mice.
AB  - Interleukin 6 (IL-6) is an important mediator of hepatocyte proliferation after
      hepatectomy. However, elevated IL-6 levels are found in patients with chronic
      liver disease. Therefore, it is unclear if hyperstimulation with IL-6 may have an
      influence on liver regeneration. We investigated whether a strong activation of
      IL-6-dependent pathways may change the course of hepatocyte proliferation after
      hepatectomy. Transgenic mice overexpressing the human soluble IL-6 receptor/gp80
      (hsgp80) in hepatocytes were stimulated with or without hepatectomy with human IL
      6 (hIL-6). Nuclear extracts were prepared and activation of gp130-dependent
      pathways was studied by Western blot and gel shift experiments. Cell cycle
      progression of hepatocytes after hepatectomy was investigated by monitoring cell
      cycle-specific factors. hIL-6 strongly activates Stat3 for more than 48 hours in
      human soluble hsgp80 transgenic mice. In contrast, no major differences were
      evident in the regulation of the Ras/MAP kinase pathway compared with wild-type
      (wt) mice. Also when hsgp80 mice were stimulated with hIL-6 3 hours before
      hepatectomy Stat3 is activated for more than 72 hours, whereas in unstimulated
      mice this event is restricted to the early hours. Strong activation of Stat3
      resulted in a delay and inhibition of hepatocyte proliferation as measured by 5
      bromo-2'-deoxyuridine (BrdU) staining and Cyclin A and E expression. This
      observation directly correlates with the induction of the cell cycle inhibitor
      p21. In summary, strong IL-6-dependent activation of Stat3 before hepatectomy
      results in delay and inhibition of cell cycle progression after hepatectomy.
      Therefore our results suggest that hyperstimulation with IL-6 can inhibit liver
      regeneration.

PMID- 10960442
TI  - Unresponsiveness of intrahepatic lymphocytes to bacterial superantigen: rapid
      development of suppressive Mac-1(high) cells in the mouse liver.
AB  - We previously found that a small dose (2 microg per mouse) of staphylococcal
      enterotoxin B (SEB) induced early emerging unresponsiveness in intrahepatic
      lymphocyte populations (IHLs). The purpose of this study was to reveal the
      inducing role of accessory cells involved in IHLs in this phenomenon. IHLs
      prepared at 3 to 24 hours after SEB injection failed to proliferate in response
      not only to SEB but also to SEA, representing ligand-nonspecific
      unresponsiveness, whereas spleen cells (SPCs) and mesenteric lymph-node cells
      showed transient proliferation. Unresponsiveness in IHLs was related to a deficit
      of their accessory cell function as measured by coculture of irradiated IHLs and
      antigen-specific, type 1 T-helper (Th1) clone cells. High levels of nitrite were
      detected in the culture supernatant. Supplement of N(G)-monomethyl-L-arginine
      lowered nitrite levels and concurrently restored the proliferative response of
      Th1 cells, indicating the involvement of nitric oxide in suppression. Adherent
      cells prepared from IHLs well reproduced these results. As shown by flow
      cytometry, Mac-1(high) Ia(+) cells, which mainly included F4/80(+) cells
      (macrophages) and a minor population of CD11c(+) cells (dendritic cells),
      increased in proportion in IHLs but not in SPCs at 6 to 24 hours. Depletion of
      Mac-1(high) cells from IHLs with antibody-coated magnetic beads recovered the
      proliferative response. Depleted Mac-1(high) cells had a monocytoid appearance.
      In immunostained sections, Kupffer cells came to highly express both Mac-1 and Ia
      at 12 hours. These results indicate that Mac-1(high)Ia(+) adherent cells, largely
      Kupffer cells activated by SEB, nonspecifically suppress the proliferation of Th1
      cells via nitric oxide production before manifestation of ligand-specific
      unresponsiveness.

PMID- 10960444
TI  - Expression and antitumor effects of TRAIL in human cholangiocarcinoma.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2L has
      been recently identified as important in promoting programmed cell death in
      breast and colon adenocarcinomas. In this study, we investigated the expression
      and therapeutic potential of TRAIL in cholangiocarcinoma, one of the most
      devastating human hepatic malignancies. Expression of TRAIL receptors was
      determined in 13 patients with resectable intrahepatic cholangiocarcinoma.
      Cellular effects of TRAIL in promoting apoptosis of human cholangiocarcinoma
      cells were analyzed after exposure to recombinant protein, as well as following
      transfection with a cDNA expression construct. In vivo effects of TRAIL on tumor
      growth were investigated after subcutaneous injection of cholangiocarcinoma cells
      into nude mice. Analysis of 13 clinical and tissue samples revealed that TRAIL
      receptors containing the death domain were present in all cholangiocarcinomas as
      well as paired normal hepatic tissues derived from surgically resected margins.
      In contrast, 7 tumors did not express the TRAIL decoy receptors lacking the death
      domain; such receptors were detectable in all of the normal hepatic tissue
      counterparts. Recombinant TRAIL induced extensive programmed cell death in
      cholangiocarcinoma cell lines lacking decoy receptor expression. Transfection of
      the ectodomain of TRAIL also induced cellular apoptosis; this effect was
      abolished by introduction of the generalized lymphoproliferative disease-like
      mutation in the TRAIL protein. Finally, in vivo administration of recombinant
      TRAIL substantially inhibited subcutaneous tumor growth of human
      cholangiocarcinoma cells. Induction of apoptosis in tumor cells is possible with
      a biologically active TRAIL, and suggests that this cytokine is a promising
      antitumor agent against human cholangiocarcinoma.

PMID- 10960445
TI  - Epidermal growth factor impairs the cytochrome C/caspase-3 apoptotic pathway
      induced by transforming growth factor beta in rat fetal hepatocytes via a
      phosphoinositide 3-kinase-dependent pathway.
AB  - Transforming growth factor beta (TGF-beta)-mediated apoptosis is one of the major
      death processes in the liver. We have previously shown that epidermal growth
      factor (EGF) is an important survival signal for TGF-beta-induced apoptosis in
      fetal hepatocytes (Fabregat et al., FEBS Lett 1996;384:14-18). In this work we
      have studied the intracellular signaling implicated in the protective effect of
      EGF. We show here that EGF activates p42 and p44 mitogen-activated protein
      kinases (MAPK). However, mitogen extracellular kinase (MEK) inhibitors do not
      block the survival effect of EGF. EGF also activates phosphoinositide 3-kinase
      (PI 3-kinase) and protein kinase B (PKB/AKT) in these cells. The presence of PI 3
      kinase inhibitors blocks the protective effect of EGF on cell viability, DNA
      fragmentation, and caspase-3 activity. We have found that TGF-beta disrupts the
      mitochondrial transmembrane potential (DeltaPsi(m))( )and activates the release
      of cytochrome c, this effect being blocked by EGF, via a PI 3-kinase-dependent
      pathway. A detailed study on bcl-2 superfamily gene expression shows that TGF
      beta produces a decrease in the messenger RNA (mRNA) and protein levels of bcl
      x(L), an antiapoptotic member of this family, capable of preventing cytochrome c
      release. EGF is able to maintain bcl-x(L) levels even in the presence of TGF
      beta. PI 3-kinase inhibitors completely block the protective effect of EGF on TGF
      beta-induced bcl-x(L )down-regulation. We conclude that PI 3-kinase mediates the
      survival effect of EGF on TGF-beta-induced death by acting upstream from the
      mitochondrial changes, i.e., preventing bcl-x(L) down-regulation, cytochrome c
      release, and activation of caspase-3.

PMID- 10960446
TI  - Subclinical seizure activity and prophylactic phenytoin infusion in acute liver
      failure: a controlled clinical trial.
AB  - Subclinical seizure activity in the patient with encephalopathy and on
      ventilation with acute liver failure (ALF) is a poorly recognized entity. Its
      importance lies in the likely exacerbation of cerebral hypoxia and the
      contribution of such seizure activity to the development of cerebral edema. The
      aim of the present study was to document the frequency of subclinical seizure
      activity in a cohort of patients with ALF by using a cerebral function and
      activity monitor that allows continuous recording of electroencephalogram
      activity at the bedside and to determine whether the prophylactic administration
      of the antiepileptic agent phenytoin would reduce its occurrence. Forty-two
      patients were enrolled in a controlled clinical trial: 20 patients were given
      phenytoin and 22 acted as controls. Subclinical seizure activity was recorded in
      3 and 10 patients, respectively, of the treated and control groups. Pupillary
      abnormalities indicative of seizure activity and/or raised intracranial pressure
      (ICP) were also seen less frequently in the phenytoin-treated group compared with
      the controls (5 and 11 patients, respectively). Autopsy examinations available in
      19 patients showed signs of cerebral edema in only 2 (22%) of the phenytoin
      treated patients compared with 7 (70%) of the controls (P <.033). Based on these
      findings, we recommend that patients with ALF, on reaching the stage of grade III
      or IV encephalopathy, should be routinely monitored for subclinical seizure
      activity. In this study, prophylaxis with phenytoin reduced the frequency of such
      seizure activity and its effects, and proved to be safe with the regimen used.

PMID- 10960447
TI  - Glycine prevents apoptosis of rat sinusoidal endothelial cells caused by
      deprivation of vascular endothelial growth factor.
AB  - Apoptosis of sinusoidal endothelial cells (SECs) is one of the initial events in
      the development of ischemia-reperfusion injury of the liver. Glycine has been
      shown to diminish ischemia-reperfusion injury in the liver and improve graft
      survival in the rat liver transplantation model. Here, we investigated the effect
      of glycine on apoptosis of primary cultured rat SECs induced by vascular
      endothelial growth factor (VEGF) deprivation. Isolated rat SECs were cultured in
      EBM-2 medium supplemented with 10% fetal bovine serum (FBS) and growth factors
      including 20 ng/mL VEGF for 3 days. SECs at 3 days of culture showed spindle-like
      shapes; however, cells started shrinking and detaching from dishes by VEGF
      deprivation. Apoptosis was detected by terminal deoxynucleotidyl transferase
      (TdT)-mediated d-uridine triphosphate (dUTP)-biotin nick end labeling (TUNEL)
      staining in these conditions. Control SECs contained only a few percent of TUNEL
      positive cells; however, they started increasing 4 hours after VEGF deprivation,
      and the percentage of TUNEL-positive cells reached about 50% at 8 hours and
      almost 100% at 16 hours after VEGF deprivation. Interestingly, this increase in
      TUNEL-positive cells after VEGF deprivation was prevented significantly when
      glycine (1-10 mmol/L) was added to the medium, the levels being around 60% of
      VEGF deprivation without glycine. Furthermore, strychnine (1 micromol/L), a
      glycine receptor antagonist, inhibited this effect of glycine, suggesting the
      possible involvement of the glycine receptor/chloride channel in the mechanism.
      Moreover, Bcl-2 protein levels in SECs were decreased 8 hours after VEGF
      deprivation, which was prevented almost completely by glycine. It is concluded
      that glycine prevents apoptosis of primary cultured SECs under VEGF deprivation.

PMID- 10960448
TI  - Critical role of reactive oxygen species and mitochondrial permeability
      transition in microcystin-induced rapid apoptosis in rat hepatocytes.
AB  - Microcystin-LR (M-LR) is a specific hepatotoxin. At present, the exact toxic
      mechanism of its action remains unclear though apoptosis is believed to be
      involved. This study was designed to investigate the role of reactive oxygen
      species (ROS) and mitochondrial permeability transition (MPT) in the M-LR-induced
      apoptotic process. Morphologic changes such as cell shrinkage, externalization of
      cell membrane phosphatidylserine, DNA fragmentation, and nuclear condensation
      suggest that M-LR causes rapid apoptosis in hepatocytes. Confocal microscopy
      revealed that M-LR exposure led to the onset of MPT and mitochondrial
      depolarization, evidenced by (1) redistribution of calcein fluorescence from
      cytosol to mitochondria, and (2) loss of mitochondrial tetramethyrhodamine methyl
      ester (TMRM) fluorescence; both occurred before apoptosis. Moreover, there was a
      significant and rapid increase of ROS level before the onset of MPT and loss of
      MMP, indicating a critical role of ROS in M-LR-induced apoptosis. Deferoxamine
      (DFO), an iron chelator, prevented the increase of ROS production, delayed the
      onset of MPT, and, subsequently, cell death. In addition, a specific MPT
      inhibitor, cyclosporin A (CsA), blocked the M-LR-induced ROS formation, onset of
      MPT, and mitochondrial depolarization as well as cell death. Thus, we conclude
      that the M-LR-induced ROS formation leads to the onset of MPT and apoptosis.

PMID- 10960449
TI  - Altered gene expression in the liver of gamma-glutamyl transpeptidase-deficient
      mice.
AB  - We used mice deficient in gamma-glutamyl transpeptidase (GGT) to analyze the
      effects of GGT deficiency and altered thiol levels on gene expression in liver.
      GGT-deficient mice have markedly reduced levels of glutathione (GSH), cysteine,
      methionine, and cysteinylglycine in liver. Steady-state RNA levels of the
      catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCS), the rate
      limiting enzyme in GSH synthesis, are elevated 4-fold in these mice, while those
      for glutathione synthetase (GSH syn) are elevated 2-fold. RNA levels of
      cystathionase (cystathionine gamma-lyase), a key enzyme in the synthesis of
      cysteine from methionine, are elevated approximately 3.5-fold. In contrast,
      levels of RNA coding for multidrug resistance protein 2 (MRP2), which transports
      GSH into bile, are half wild-type values. We found no change in RNA levels of
      enzymes related to oxidative injury (CuZn and Mn superoxide dismutases [SOD],
      catalase, and glutathione peroxidase). Similarly, RNA levels of glutathione
      reductase and ribonucleotide reductase were unchanged. Furthermore, in contrast
      to previous in vitro results, methyl methanesulfonate did not induce stress
      activated signal transduction as measured by c-jun phosphorylation in livers of
      GGT-deficient mice, despite further depletion of GSH by buthionine sulfoximine.
      Our findings indicate that GGT deficiency itself and/or altered thiol levels
      regulate expression of genes involved in GSH metabolism, but have no effect on
      the expression of other antioxidant genes.

PMID- 10960450
TI  - Effect of bilirubin UDP glucuronosyltransferase 1 gene TATA box genotypes on
      serum bilirubin concentrations in chronic liver injuries.
AB  - TATA box abnormality in the promoter region of the bilirubin UDP
      glucuronosyltransferase 1 gene has been reported to cause Gilbert's syndrome in
      white subjects. It has also been reported that the majority of Japanese patients
      with Gilbert's syndrome are heterozygous for Gly71Arg in the coding region of
      this gene. On the other hand, some patients with chronic hepatitis often show
      signs of unexpected hyperbilirubinemia. The aims of this study were to determine
      which of the genetic variations, TATA box genotype or codon 71 genotype, is most
      closely related to serum bilirubin concentrations, and whether the TATA box
      genotype has an effect on serum bilirubin concentrations in patients with
      hepatitis C-associated chronic liver diseases. In a sample of 300 individuals
      selected from among the general Japanese population, mean concentrations of total
      serum bilirubin differed significantly among TATA box genotypes, but not among
      codon 71 genotypes. Concentration of total serum bilirubin was significantly
      correlated with TATA box genotypes. In 211 patients with hepatitis C-associated
      chronic liver diseases, mean concentrations of total serum bilirubin also
      differed significantly among TATA box genotypes. In patients with chronic
      hepatitis C, concentration of total serum bilirubin was significantly correlated
      with TATA box genotypes. In summary, TATA box genotypes, but not codon 71
      genotypes, are closely related to serum bilirubin concentrations. TATA box
      genotypes should therefore be considered when evaluating hepatic function by
      serum bilirubin concentrations in cases of hepatitis C-associated chronic liver
      diseases.

PMID- 10960451
TI  - Radial artery wall alterations in genetic hemochromatosis before and after iron
      depletion therapy.
AB  - Iron overload is believed to have an adverse influence on the cardiovascular
      system and animal studies have shown that iron may be involved in the events that
      lead to atherosclerosis via an enhancement of smooth muscle cell proliferation,
      lipid oxidation, and free radical production. There are no data on the effect of
      iron overload on arterial structural and mechanical properties in humans. We
      measured wall thickness and distensibility (D) by ultrasonography of the radial
      artery in 12 patients with uncomplicated genetic hemochromatosis (GH) who were
      normotensive and without atherosclerotic plaques. Twelve age- and sex-matched
      patients were taken as controls. Nine patients were evaluated also after iron
      depletion. Wall thickness was greater in patients with GH than in controls (+50%,
      P <.01) whereas D was slightly reduced in the former group compared with the
      latter group, though the difference was not statistically significant. After iron
      depletion, a significant reduction of wall thickness and a significant increase
      in D were observed (-24% and +33%, P <.05 for both). Thus, in patients with
      hemochromatosis, arterial wall thickness is increased before the onset of
      cardiovascular complications. This alteration is reverted by iron depletion,
      which also can improve the initial and modest radial artery wall stiffening
      associated with this condition. Thus, functional and structural alterations in
      midsize muscle arteries may be an early abnormality of hemochromatosis.

PMID- 10960452
TI  - JAGGED1 gene expression during human embryogenesis elucidates the wide phenotypic
      spectrum of Alagille syndrome.
AB  - Mutations of the JAGGED1 gene, encoding a NOTCH receptor ligand, cause Alagille
      syndrome (AGS), a complex malformative disorder affecting mainly the liver,
      heart, vertebrae, eye, and face. Minor and occasional features involving kidney,
      pharynx, systemic arteries, skeleton, and ear are in some cases associated with
      the syndrome. To describe the expression of JAGGED1 during human embryogenesis
      and to study its relationship with all the features of AGS, we performed in situ
      hybridization studies on human embryos and fetal tissue sections. JAGGED1 was
      mainly expressed in the cardiovascular system. In the liver, JAGGED1 transcripts
      were only detected in blood vessels. JAGGED1 was also expressed in other
      structures of mesenchymal origin (distal mesenchyme of limb buds; mesonephric and
      metanephric tubules of the kidney) and in epithelial structures including the
      ciliary margin of the retina and the posterior part of the lens, the ventral
      epithelium of the otic vesicle, the neurosensory epithelium of the ear vestibule,
      the epithelium of pharyngeal arches, and the developing central nervous system.
      The strong JAGGED1 expression during human embryo- and feto-genesis both in the
      vascular system and in other mesenchymal and epithelial tissues implicates
      abnormal angiogenesis in the pathogenesis of Alagille syndrome and particularly
      the paucity of interlobular bile ducts. However, it is probably not the only
      mechanism of the disease. Except for the central nervous system, there is a
      strong correlation between JAGGED1 expression and all the features of AGS. This
      implies that the features occasionally associated with the syndrome are not
      coincidental.

PMID- 10960453
TI  - Assessment of long-term outcomes of community-acquired hepatitis C infection in a
      cohort with sera stored from 1971 to 1975.
AB  - The aim of this study was to examine the long-term effects of hepatitis C virus
      (HCV) infection on a cohort of patients admitted with acute viral hepatitis from
      1971 through 1975. The availability of stored sera from this time enabled testing
      to identify those who were anti-HCV-positive on admission. Sixteen percent (n =
      238) of the cohort tested anti-HCV-positive. The unexposed group was selected
      from those who were anti-HCV-negative. Systematic approaches were used to locate
      the cohort and health outcomes assessed by a study-specific questionnaire and
      clinical, serological, virological, and biochemical assessment. Complete follow
      up was achieved on 98 anti-HCV-positive individuals and 201 negatives. Injecting
      drug use (IDU) was the presumed route of infection. At a mean of 25 years' follow
      up, 54% of the anti-HCV-positive group had evidence of chronic HCV infection
      (both anti-HCV- and HCV-RNA-positive); the remainder were HCV-RNA-negative. Sixty
      nine percent of those chronically infected had elevated serum alanine
      transaminase (ALT) levels, but only 8% had progressed to overt cirrhosis, and no
      cases of hepatocellular carcinoma (HCC) were identified. In summary, anti-HCV
      positive subjects were 8 times more likely to have died from suicide or drug
      overdose than from HCV-related disease. Anti-HCV-positive study subjects were at
      increased risk of liver-related pathology after 25 years' follow-up, but few had
      progressed to overt cirrhotic liver disease. Excess mortality in this group was
      not the result of liver disease. This suggests that the natural history of
      community-acquired HCV may be more benign than previously thought.

PMID- 10960454
TI  - Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal
      antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees.
AB  - Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen
      (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41
      and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg
      binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41 recognizes a
      conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5
      recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV)
      subtypes with distinct patterns. The neutralizing activity of these antibodies
      was tested in 2 different animal model systems. Administration of each mAb to HBV
      Trimera mice, a system that provides a mouse model for human hepatitis B
      infection, reduced the viral load and the percentage of HBV-DNA-positive mice in
      a dose-dependent manner. These 2 mAbs were more effective than a polyclonal
      antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both
      inhibition of HBV liver infection and reduction of viral load. A single
      administration of a mixture of these mAbs into HBV chronic carrier chimpanzees
      resulted in immediate reduction in HBsAg levels followed by recurrence to initial
      levels within few days. Thus, these mAbs may be potential candidates for
      preventive therapy or in combination with other antiviral agents against HBV.
      Further studies in humans are needed to assess these mAbs in various clinical
      indications.

PMID- 10960456
TI  - Prednisolone priming enhances Th1 response and efficacy of subsequent lamivudine
      therapy in patients with chronic hepatitis B.
AB  - Asian lamivudine trial has shown that hepatitis B e antigen (HBeAg)
      seroconversion rate during 1 year of lamivudine therapy was only 16% but was 64%
      in the subgroup of patients with a pretherapy serum alanine transaminase (ALT)
      level over 5 times the upper limit of normal (ULN). To test whether ALT rebound
      following corticosteroid priming enhances response to lamivudine therapy, a pilot
      study was conducted in 30 patients with ALT levels less than 5x ULN (43-169; N <
      36 U/L). They received 30 mg of prednisolone daily for 3 weeks, 15 mg daily for 1
      week, no treatment for 2 weeks, and then 150 mg of lamivudine daily for 9 months.
      Complete response (CR) was defined as ALT normalization with HBV-DNA
      seroclearance and HBeAg seroconversion. Peripheral blood mononuclear cell
      proliferation and cytokine secretion in response to recombinant HBV core antigen
      were serially assayed in 7 patients during priming and after withdrawal of
      prednisolone. Clinical rebound with an ALT over 5x ULN was observed in 20
      patients (67%). Of these 20, 12 (60%) showed CR as compared with 1 (10%) of the
      10 patients without significant ALT rebound (P <.002). The HBeAg seroconversion
      sustained in 70% of the patients 3 to 6 months after the end of lamivudine
      therapy. Immunological assays revealed that the responders showed Th1 dominant
      response and higher stimulation index to prednisolone priming. No serious side
      effect was encountered. These results suggest that corticosteroid priming induced
      immune/ALT rebound greatly enhances response to lamivudine therapy in chronic
      hepatitis B. Confirmation by randomized controlled trial is needed.

PMID- 10960455
TI  - Liver-derived hepatitis C virus (HCV)-specific CD4(+) T cells recognize multiple
      HCV epitopes and produce interferon gamma.
AB  - Virus-specific CD4(+) T-cell response at the site of inflammation is believed to
      play a decisive role for the course of viral disease. In hepatitis C virus (HCV)
      infection, the majority of studies focused on the peripheral blood T-cell
      response. In this study we analyzed intrahepatic virus-specific CD4(+) T-cell
      response and compared this with that in the peripheral blood. Liver and blood
      derived T-cell lines were studied in 36 patients (18 with chronic hepatitis C and
      18 with HCV-associated cirrhosis). Virus-specific interferon gamma (IFN-gamma)
      production at a single cell level to various HCV-proteins (core, nonstructural
      [NS] 3/4, NS5) were determined by enzyme-linked immunospot (ELIspot). Phenotyping
      was done by fluorescent-activated cell sorter analysis. In approximately half (16
      of 36 [44%]) of intrahepatic T-cell lines a significant number of IFN-gamma spots
      were observed, whereas this was the case in only 19% (7 of 36 T-cell lines) in
      the blood. In relative terms, core and nonstructural proteins were recognized
      with the same frequency in both compartments, but HCV-specificity was
      significantly more often detected in liver tissue compared with the blood.
      Hepatitis activity index, viral load, and alanine transaminase levels did not
      correlate with the detection of HCV-specific CD4(+) T cells. All T-cell lines
      were dominated by CD4(+) T cells. In conclusion, HCV-specific CD4(+) T cells are
      multispecific, compartmentalize to the liver, and produce IFN-gamma. We speculate
      that our data would support the concept of compartmentalization of specific T
      cells at the site of inflammation and that a low frequency of specific T cells is
      associated with failure to clear the virus and a chronic course of disease.

PMID- 10960457
TI  - Antibodies against hepatitis C virus-like particles and viral clearance in acute
      and chronic hepatitis C.
AB  - We recently described the efficient assembly of hepatitis C virus (HCV)
      structural proteins into HCV-like particles (HCV-LPs) in insect cells. These
      noninfectious HCV-LPs have similar morphologic and biophysical properties as
      putative virions isolated from HCV-infected humans and can induce a broadly
      directed immune response in animal models. The HCV envelope proteins of HCV-LPs
      are presumably presented in a native, virion-like conformation and may therefore
      interact with antienvelope antibodies directed against conformational epitopes.
      In this study, HCV-LPs were used as capture antigens in an enzyme-linked
      immunosorbent assay (ELISA) to detect and quantify antibodies against HCV
      structural proteins in patients with acute and chronic hepatitis C. High titers
      of anti-HCV-LP antibodies were detected in patients chronically infected with HCV
      genotypes 1 to 6. In contrast to individuals with chronic hepatitis C, patients
      with acute self-limited hepatitis C displayed only a transient and weak
      seroreactivity against HCV-LPs. Patients with chronic HCV infection successfully
      treated with interferon demonstrated a gradual decline of anti-HCV-LP titers
      during or subsequent to viral clearance. Sustained interferon responders were
      characterized by significantly higher pretreatment levels of anti-HCV-LP
      antibodies as compared with nonresponders (P =.0001). In conclusion, HCV
      infection is associated with limited humoral immunity against the envelope
      proteins present on the HCV-LPs. An HCV-LP-based ELISA may be a useful diagnostic
      tool to distinguish acute hepatitis C from chronic HCV infection with
      exacerbation, and to predict viral clearance in response to interferon.

PMID- 10960458
TI  - Vaccination of chimpanzees with plasmid DNA encoding the hepatitis C virus (HCV)
      envelope E2 protein modified the infection after challenge with homologous
      monoclonal HCV.
AB  - Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide.
      Development of vaccines to prevent HCV infection, or at least prevent progression
      to chronicity, is a major goal. In mice and rhesus macaques, a DNA vaccine
      encoding cell-surface HCV-envelope 2 (E2) glycoprotein stimulated stronger immune
      responses than a vaccine encoding intracellular E2. Therefore, we used DNA
      encoding surface-expressed E2 to immunize chimpanzees 2768 and 3001. Chimpanzee
      3001 developed anti-E2 after the second immunization and antibodies to
      hypervariable region 1 (HVR1) after the third immunization. Although chimpanzee
      2768 had only low levels of anti-E2 after the third immunization, an anamnestic
      response occurred after HCV challenge. CTL responses to E2 were not detected
      before challenge, but a strong response was detected after HCV challenge in
      chimpanzee 2768. An E2-specific CD4+ response was detected in chimpanzee 2768
      before challenge and in both chimpanzees postchallenge. Three weeks after the
      last immunization, animals were challenged with 100 50% chimpanzee-infectious
      doses (CID(50)) of homologous monoclonal HCV. As a control, a naive chimpanzee
      was inoculated with 3 CID(50) of the challenge virus. The vaccine did not
      generate sterilizing immunity because both vaccinated chimpanzees were infected.
      However, both vaccinated chimpanzees resolved the infection early whereas the
      control animal became chronically infected. Compared with the control animal,
      hepatitis appeared earlier in the course of the infection in both vaccinated
      chimpanzees. Therefore, DNA vaccine encoding cell surface-expressed E2 did not
      elicit sterilizing immunity in chimpanzees against challenge with a monoclonal
      homologous virus, but did appear to modify the infection and might have prevented
      progression to chronicity.

PMID- 10960459
TI  - High-throughput quantitative analysis of hepatitis B virus DNA in serum using the
      TaqMan fluorogenic detection system.
AB  - Reproducible quantitative assays to detect viral nucleic acids have proven useful
      in defining disease progression and following response to therapy in a wide
      variety of viral infections. We describe the development of a quantitative assay
      to detect hepatitis B virus (HBV) DNA using real-time fluorescent-probe
      polymerase chain reaction (PCR) (TaqMan). The assay is highly reproducible,
      highly automated, and much more sensitive than the currently used branched-chain
      DNA (bDNA) assay for HBV. The quantitative PCR assay accurately detected samples
      ranging from 10 to 10(9) copies of HBV DNA per milliliter. Of 157 serum samples
      submitted for HBV quantitation, 119 were positive by TaqMan PCR versus only 55 by
      bDNA (P <.001). All 55 bDNA-positives were positive by TaqMan. Of the 77 samples
      with detectable HBV-DNA titers below 3.75 x 10(5) copies by TaqMan, only 13 were
      detected by bDNA. We tested 119 patients negative for all HBV serologic markers,
      and all tested negative in the TaqMan assay. HBV DNA was detected by TaqMan in
      164 of 195 (84%) of hepatitis B surface antigen (HBsAg)-positive samples. Among
      hepatitis B e antigen (HBeAg)-positive samples, median titers were 4. 3 x 10(6)
      copies/mL versus 322 copies/mL in HBeAg-negative samples (P =.012). The TaqMan
      assay for HBV DNA is highly sensitive and reproducible and thus appears useful in
      accurately defining levels of viral replication among persons with HBV infection.

PMID- 10960460
TI  - Triple antiviral therapy as a new option for patients with interferon
      nonresponsive chronic hepatitis C.
AB  - The aim of the study was to evaluate the efficacy of triple antiviral therapy
      with interferon, ribavirin, and amantadine in comparison with interferon and
      ribavirin combination treatment in patients with interferon-nonresponsive chronic
      hepatitis C. We performed an open-label, prospective randomized controlled trial
      at a secondary referral center. We used a 2:1 ratio, patients received
      interferon, ribavirin, and amantadine, or interferon and ribavirin for 12 months,
      and were followed up for an additional 6 months. Ninety-four consecutive adult
      interferon nonresponders with chronic hepatitis C were screened. Sixty
      consecutive elected patients entered the study. No patients withdrew because of
      adverse effects. Forty patients received interferon alfa (5 megaunits on
      alternate days), ribavirin (800-1,000 mg daily), and amantadine (200 mg daily)
      for 12 months, and 20 patients received the same treatment without amantadine. At
      the end of follow-up, alanine transaminase (ALT) level normalization was
      maintained in 23 of 40 patients (57%) after triple therapy, but in 2 of 20
      patients (10%) after double therapy (P <.001, RR = 2.11, 95% CI, 1.43-3.12),
      whereas disappearance of serum HCV RNA persisted in 19 of 40 patients (48%) and
      in 1 of 20 patients (5%), respectively (P <.001, RR = 1.81, 95% CI, 1.32-2.47).
      The safety profile was similar in the 2 groups. In conclusion, in patients with
      interferon-nonresponsive chronic hepatitis C, triple antiviral therapy for 1 year
      results in a high rate of sustained biochemical and virologic responses.

PMID- 10960461
TI  - Acute exacerbation of chronic hepatitis B virus infection after withdrawal of
      lamivudine therapy.
AB  - Acute exacerbations of chronic hepatitis B virus (HBV) infection occur after
      withdrawal of lamivudine therapy in approximately 16% of patients and are
      considered of little clinical significance. We observed "lamivudine withdrawal
      hepatitis" accompanied by jaundice and incipient liver failure, but also followed
      by complete recovery and viral clearance. To investigate the incidence, severity,
      timing, and virologic characteristics of "lamivudine withdrawal hepatitis" we
      monitored 41 patients for at least 6 months after discontinuation of nucleoside
      analogue therapy. The incidence of hepatitis flares was estimated to be 7 of 41
      (17%); in 2 of 41 cases (5%), hepatitis flares were associated with jaundice and
      incipient liver failure. A noticeable feature of the "lamivudine withdrawal
      hepatitis" flares were the high HBV-DNA levels at the time of the alanine
      transaminase (ALT) peak. All were wild-type HBV, even the one that emerged from a
      lamivudine-resistant strain during therapy. To minimize the risk of liver failure
      and to enhance the elimination of HBV following flares, lamivudine therapy was
      reinstituted in an icteric patient. Clinical and biochemical remission ensued,
      followed by loss of HBV DNA and hepatitis B e antigen (HBeAg) seroconversion.
      Such a virologic response did not occur in 5 other patients with a nonicteric
      "lamivudine withdrawal hepatitis," who were not retreated with lamivudine.
      Hepatitis after withdrawal of lamivudine resembles acute hepatitis B with a
      predominance of anicteric flares within a time frame of 6 months. Active
      management of hepatitis flares following withdrawal of nucleoside analogue
      therapy should be investigated further.

PMID- 10960462
TI  - Pharmacokinetics and tissue distribution of a ribozyme directed against hepatitis
      C virus RNA following subcutaneous or intravenous administration in mice.
AB  - A nuclease resistant ribozyme targeting the 5' untranslated region (5' UTR) of
      hepatitis C virus (HCV) at site 195 has been identified. To investigate the
      therapeutic utility of this ribozyme, we evaluated the pharmacokinetics and
      tissue distribution with two labeled forms of this ribozyme. [(32)P]-labeled
      ribozyme was administered as a single subcutaneous (SC) or intravenous (IV) bolus
      at a dose of 10 mg/kg or 30 mg/kg in C57Bl/6 mice. Regardless of route of
      administration, peak liver concentrations achieved were greater than the
      concentration necessary to inhibit HCV-IRES-luciferase expression in cell
      culture. The ribozyme was well absorbed after SC administration (89%) and had an
      elimination half-life of 23 minutes. To show intracellular localization of the
      ribozyme in target tissue, a tetramethyl rhodamine (TMR)-labeled ribozyme was
      administered as a single SC or IV bolus at a dose of 30 mg/kg in C57Bl/6 mice.
      Mice treated SC or IV with TMR-labeled ribozyme had positive fluorescence in the
      liver from 15 minutes to 48 hours after dosing. Definite positive fluorescence
      was still present at 72 hours in the mice dosed via the IV route. At early time
      points (15 and 30 minutes postinjection), nuclear and possibly cytoplasmic
      fluorescence was present in the hepatocytes, and sinusoidal fluorescence was
      intense. At the later time points, fluorescence became more punctate. Abundant
      staining was often present in Kupffer cells. This study confirms the retention of
      ribozyme in liver cells and supports the potential of an anti-HCV ribozyme as a
      therapeutic agent for treatment of chronic hepatitis C.

PMID- 10960464
TI  - Standardization of hepatitis C virus RNA quantification.
AB  - It was recently recommended that hepatitis C virus (HCV) RNA quantification be
      used to tailor the duration of combined interferon alfa (IFN-alpha)/ribavirin
      therapy in patients infected by HCV genotypes 1, 4, and 5. This recommendation
      has been difficult to implement in the absence of standardized quantitative units
      for HCV RNA. The aim of this work was to define clinically relevant HCV RNA loads
      in standardized international units (IU), for use in routine clinical and
      research applications based on standardized quantitative assays. Two hepatitis C
      virus RNA quantitative assays were used: (1) the Superquant assay (National
      Genetics Institute, Los Angeles, CA), for which possibly relevant thresholds were
      established; and (2) the semi-automated Cobas Amplicor HCV Monitor assay version
      2.0 (Cobas v2.0, Roche Molecular Systems, Pleasanton, CA) that measures HCV RNA
      loads in IU/mL. Quantification in the Cobas v2.0 assay was linear over the entire
      range of values tested, including viral loads higher than 850,000 IU/mL after 100
      fold dilution. The accuracy and precision of the measures in IU/mL were
      satisfactory with Cobas v2.0. The results obtained with Superquant and Cobas v2.0
      correlated (r =.932; P <.0001). A value of 2,000,000 copies/mL (6.3 log(10)
      copies/mL) with Superquant was converted to nearly 800,000 IU/mL (5.9 log(10)
      IU/mL). In conclusion, all HCV RNA quantitative assays should give HCV RNA loads
      in international units and be validated with appropriate calibrated panels;
      800,000 IU/mL in any of these assays should be used as the decision threshold to
      tailor the IFN-alpha/ribavirin treatment duration in patients infected by HCV
      genotypes 1, 4, and 5.

PMID- 10960463
TI  - A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic
      hepatitis C. The Hepatitis C Intervention Therapy Group.
AB  - The objectives of this study were to assess the safety, pharmacokinetics, and
      efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients
      with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20
      68 years) with clinically compensated chronic hepatitis C virus (HCV) were
      enrolled into this open-label, randomized, active controlled study. Patients
      received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for
      24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg
      orally daily. Patients were evaluated during treatment and after a 24-week follow
      up period for safety and efficacy. Detailed pharmacokinetic assessments were
      performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related
      reductions in white cells, neutrophils and platelets. Addition of ribavirin
      reduced hemoglobin levels in a dose-related manner, did not further reduce PEG
      Intron-induced decreases in neutrophil or white cell count, and increased
      platelet counts. Neutrophil function tests (C5a and FMLP migration, killing
      curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia)
      were qualitatively similar in all dose groups. Anti-HCV activity, as measured by
      loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment
      (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends
      for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in
      patients coadministered ribavirin than in patients treated with PEG-Intron
      monotherapy. There was no evidence of pharmacokinetic interactions with either
      drug. We conclude that the safety and tolerability of combined PEG
      Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG
      Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were
      numerically superior to those obtained with PEG-Intron monotherapy.

PMID- 10960465
TI  - Prevention of variceal rebleeding: endoscopes, drugs, and more.

PMID- 10960466
TI  - Short-term corticosteroid therapy in combination with lamivudine: A case of deja
      vu?

PMID- 10960467
TI  - Medical therapy of brain edema in fulminant hepatic failure.

PMID- 10960468
TI  - Oxidative stress as a cause of biliary lithiasis: new possibilities for medical
      therapy of stones or a false alarm?

PMID- 10960469
TI  - Iron overload and atherosclerosis.

PMID- 10960470
TI  - Analysis of estrogen receptor interaction with a repressor of estrogen receptor
      activity (REA) and the regulation of estrogen receptor transcriptional activity
      by REA.
AB  - The transcriptional activity of nuclear hormone receptors is known to be
      modulated by coregulator proteins. We found that the repressor of estrogen
      receptor activity (REA), a protein recruited to the hormone-occupied estrogen
      receptor (ER), decreased the transcriptional activity of ER, both when ER was
      acting directly through DNA response elements as well as when it was tethered to
      other transcription factors. Administration of antisense REA resulted in a 2-4
      fold increase in ER transactivation, implying that endogenous REA normally
      dampens the stimulatory response to estradiol. To define the interaction regions
      between ER and REA, we used glutathione S-transferase pull-down assays. We found
      that REA bound to the ligand-binding domain (E domain) of ER, but not to other
      regions of ER, and that REA interaction with ER involved a region in the C
      terminal half of REA. REA and the coactivator SRC-1 were involved in a functional
      competition for regulation of ER transcriptional activity, which we show results
      from competition between these two coregulators for interaction with ER. REA
      contains an LXXLL motif near its N terminus, but this motif was not involved in
      its binding to ER. Rather, this sequence was required for the competitive binding
      of REA and SRC-1 to ER and thus for optimal repression of ER activity. Our
      findings show that the regions of REA required for its interaction with ER and
      for its repression of ER activity are different.

PMID- 10960472
TI  - Hepatocytes contribute to soluble CD14 production, and CD14 expression is
      differentially regulated in hepatocytes and monocytes.
AB  - CD14 presents as a glycosylphosphatidylinositol-linked membrane protein on the
      surface of monocytes/macrophages and as a soluble protein in the serum. Our
      previous studies have shown that an 80-kilobase pair (kb) genomic DNA fragment
      containing the human CD14 gene is sufficient to direct CD14 expression in a
      monocyte-specific manner in transgenic mice. In addition, we discovered that
      human CD14 is highly expressed in hepatocytes. Here, we report the generation of
      transgenic mice with either a 24- or 33-kb human CD14 genomic DNA fragment. Data
      from multiple transgenic lines show that neither the 24- nor the 33-kb transgenic
      mice express human CD14 in monocytes/macrophages. However, human CD14 is highly
      expressed in the liver of the 33-kb transgenic mice. These results demonstrate
      that human CD14 expression is regulated differently in monocytes and hepatocytes.
      Furthermore, we identified an upstream regulatory element beyond the 24-kb
      region, but within the 33-kb region of the human CD14 gene, which is critical for
      CD14 expression in hepatocytes, but not in monocytes/macrophages. Most
      importantly, the data demonstrate that the liver is one of the major organs for
      the production of soluble CD14. These transgenic mice provide an excellent system
      to further explore the functions of soluble CD14.

PMID- 10960471
TI  - Characterization of the binding site on the formyl peptide receptor using three
      receptor mutants and analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu.
AB  - The formyl peptide receptor (FPR) is a chemotactic G protein-coupled receptor
      found on the surface of phagocytes. We have previously shown that the formyl
      peptide binding site maps to the membrane-spanning region (Miettinen, H. M.,
      Mills, J. S., Gripentrog, J. M., Dratz, E. A., Granger, B. L., and Jesaitis, A.
      J. (1997) J. Immunol. 159, 4045-4054). Recent reports have indicated that non
      formylated peptides, such as MMWLL can also activate this receptor (Chen, J.,
      Bernstein, H. S., Chen, M., Wang, L., Ishi, M., Turck, C. W., and Coughlin, S. R.
      (1995) J. Biol. Chem. 270, 23398-23401.) Here we show that the selectivity for
      the binding of different NH(2)-terminal analogs of MMWLL or MLF can be markedly
      altered by mutating Asp-106 to asparagine or Arg-201 to alanine. Both D106N and
      R201A produced a similar change in ligand specificity, including an enhanced
      ability to bind the HIV-1 peptide DP178. In contrast, the mutation R205A
      exhibited altered specificity at the COOH terminus of fMLF, with R205A binding
      fMLF-O-butyl > fMLF-O-methyl > fMLF, whereas wt FPR bound fMLF > fMLF-O-methyl
      approximately fMLF-O-butyl. These data, taken together with our previous finding
      that the leucine side chain of fMLF is probably bound to FPR near FPR (93)VRK(95)
      (Mills, J. S., Miettinen, H. M., Barnidge, D., Vlases, M. J., Wimer-Mackin, S.,
      Dratz, E. A., and Jesaitis, A. J. (1998) J. Biol. Chem. 273, 10428-10435.),
      indicate that the most likely positioning of fMLF in the binding pocket of FPR is
      approximately parallel to the fifth transmembrane helix with the formamide group
      of fMLF hydrogen-bonded to both Asp-106 and Arg-201, the leucine side chain
      pointing toward the second transmembrane region, and the COOH-terminal carboxyl
      group of fMLF ion-paired with Arg-205.

PMID- 10960474
TI  - A covariant change of the two highly conserved bases in the GTPase-associated
      center of 28 S rRNA in silkworms and other moths.
AB  - The GTPase-associated center in 23/28 S rRNA is one of the most conserved
      functional domains throughout all organisms. We detected a unique sequence of
      this domain in Bombyx mori species in which the bases at positions 1094 and 1098
      (numbering from Escherichia coli 23 S rRNA) are C and G instead of the otherwise
      universally conserved bases U and A, respectively. These changes were also
      observed in four other species of moths, but not in organisms other than the
      moths. Characteristics of the B. mori rRNA domain were investigated by native
      polyacrylamide gel electrophoresis using RNA fragments containing residues 1030
      1128. Although two bands of protein-free RNA appeared on gel, they shifted to a
      single band when bound to Bombyx ribosomal proteins Bm-L12 and Bm-P complex,
      equivalent to E. coli L11 and L8, respectively. Bombyx RNA showed lower binding
      capacity than rat RNA for the ribosomal proteins and anti-28 S autoantibody,
      specific for a folded structure of the eukaryotic GTPase-associated domain. When
      the C(1094)/G(1098) bases in Bombyx RNA were replaced by the conserved U/A bases,
      the protein-free RNA migrated as a single band, and the complex formation with Bm
      L12, Bm-P complex, and anti-28 S autoantibody was comparable to that of rat RNA.
      The results suggest that the GTPase-associated domain of moth-type insects has a
      labile structural feature that is caused by an unusual covariant change of the
      U(1094)/A(1098) bases to C/G.

PMID- 10960473
TI  - Regulation of glucose-6-phosphatase gene expression by protein kinase Balpha and
      the forkhead transcription factor FKHR. Evidence for insulin response unit
      dependent and -independent effects of insulin on promoter activity.
AB  - Glucose-6-phosphatase plays an important role in the regulation of hepatic
      glucose production, and insulin suppresses glucose-6-phosphatase gene expression.
      Recent studies indicate that protein kinase B and Forkhead proteins contribute to
      insulin-regulated gene expression in the liver. Here, we examined the role of
      protein kinase B and Forkhead proteins in mediating effects of insulin on glucose
      6-phosphatase promoter activity. Transient transfection studies with reporter
      gene constructs demonstrate that insulin suppresses both basal and
      dexamethasone/cAMP-induced activity of the glucose-6-phosphatase promoter in
      H4IIE hepatoma cells. Both effects are partially mimicked by coexpression of
      protein kinase Balpha. Coexpression of the Forkhead transcription factor FKHR
      stimulates the glucose-6-phosphatase promoter activity via interaction with an
      insulin response unit (IRU), and this activation is suppressed by protein kinase
      B. Coexpression of a mutated form of FKHR that cannot be phosphorylated by
      protein kinase B abolishes the regulation of the glucose-6-phosphatase promoter
      by protein kinase B and disrupts the ability of insulin to regulate the glucose-6
      phosphatase promoter via the IRU. Mutation of the insulin response unit of the
      glucose-6-phosphatase promoter also prevents the regulation of promoter activity
      by FKHR and protein kinase B but only partially impairs the ability of insulin to
      suppress both basal and dexamethasone/cAMP-stimulated promoter function. Taken
      together, these results indicate that signaling by protein kinase B to Forkhead
      proteins can account for the ability of insulin to regulate glucose-6-phosphatase
      promoter activity via the IRU and that other mechanisms that are independent of
      the IRU, protein kinase B, and Forkhead proteins also are important in mediating
      effects of in insulin on glucose-6-phosphatase gene expression.

PMID- 10960475
TI  - Dissecting sites important for complement regulatory activity in membrane
      cofactor protein (MCP; CD46).
AB  - Membrane cofactor protein (MCP; CD46), a widely distributed regulator of
      complement activation, is a cofactor for the factor I-mediated degradation of C3b
      and C4b deposited on host cells. MCP possesses four extracellular, contiguous
      complement control protein modules (CCPs) important for this inhibitory activity.
      The goal of the present study was to delineate functional sites within these
      modules. We employed multiple approaches including mutagenesis, epitope mapping,
      and comparisons to primate MCP to make the following observations. First,
      functional sites were located to each of the four CCPs. Second, some residues
      were important for both C3b and C4b interactions while others were specific for
      one or the other. Third, while a reduction in ligand binding was invariably
      accompanied by a parallel reduction in cofactor activity (CA), other mutants lost
      or had reduced CA but retained ligand binding. Fourth, two C4b-regulatory domains
      overlapped measles virus interactive regions, indicating that the hemagglutinin
      docks to a site important for complement inhibition. Fifth, several MCP
      regulatory areas corresponded to functionally critical, homologous positions in
      other CCP-bearing C3b/C4b-binding proteins. Based on these data and the recently
      derived crystal structure of repeats one and two, computer modeling was employed
      to predict MCP structure and examine active sites.

PMID- 10960476
TI  - Loss of [13C]glycerol carbon via the pentose cycle. Implications for
      gluconeogenesis measurement by mass isotoper distribution analysis.
AB  - Whereas many reports substantiated the suitability of using [2-(13)C]glycerol and
      Mass Isotoper Distribution Analysis for gluconeogenesis, the use of
      [(13)C]glycerol had been shown to give lower estimates of gluconeogenesis (GNG).
      The reason for the underestimation has been attributed to asymmetric isotope
      incorporation during gluconeogenesis as well as zonation of gluconeogenic enzymes
      and a [(13)C]glycerol gradient across the liver. Since the cycling of glycerol
      carbons through the pentose cycle pathways can introduce asymmetry in glucose
      labeling pattern and tracer dilution, we present here a study of the role of the
      pentose cycle in gluconeogenesis in Fao cells. The metabolic regulation of
      glucose release and gluconeogenesis by insulin was also studied. Serum-starved
      cells were incubated for 24 h in Dulbecco's modified Eagle's media containing 1.5
      mm [U-(13)C]glycerol. Mass isotopomers of whole glucose from medium or glycogen
      and those of the C-1-C-4 fragment were highly asymmetrical, typical of that
      resulting from the cycling of glucose carbon through the pentose cycle.
      Substantial exchange of tracer between hexose and pentose intermediates was
      observed. Our results offer an alternative mechanism for the asymmetrical
      labeling of glucose carbon from triose phosphate. The scrambling of (13)C in
      hexose phosphate via the pentose phosphate cycle prior to glucose release into
      the medium is indistinguishable from dilution of labeled glucose by glycogen
      using MIDA and probably accounts for the underestimation of GNG using (13)C
      tracer methods.

PMID- 10960477
TI  - CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate cytidyltransferase in the
      methanogenic archaeon Methanothermobacter thermoautotrophicus.
AB  - CDP-2,3-di-O-geranylgeranyl-sn-glycerol synthase (CDP-archaeol synthase) activity
      was discovered in the membrane fraction of the methanoarchaeon
      Methanothermobacter thermoautotrophicus cells. It catalyzed the formation of CDP
      2,3-di-O-geranylgeranyl-sn-glycerol from CTP and 2,3-di-O-geranylgeranyl-sn
      glycero-1-phosphate (unsaturated archaetidic acid). The identity of the reaction
      product was confirmed by thin layer chromatography, fast atom bombardment-mass
      spectroscopy, chemical analysis, and by UV spectroscopy. One mole of the product
      was formed from approximately 1 mol of each of the reactants. The enzyme showed
      maximal activity at pH 8.5 and 55 degrees C in the presence of Mg(2+) and K(+)
      ions. By in vivo pulse labeling of phospholipids with (32)P(i), CDP-archaeol was
      found to be an intracellular intermediate. A cell-free homogenate of M.
      thermoautotrophicus, when incubated with l-serine, converted the product of CDP
      archaeol synthase reaction to a product with the same chromatographic mobility as
      archaetidylserine. It was concluded from these results that both CDP-archaeol and
      CDP-archaeol synthase were involved in cellular phospholipid biosynthesis. Among
      various synthetic substrate analogs, both enantiomers of unsaturated archaetidic
      acid possessing geranylgeranyl chains showed similar levels of activity, while
      archaetidic acid with saturated or monounsaturated isoprenoid or straight chains
      was a poor substrate, despite having the same stereostructure as the fully active
      substrate. The ester analogs with geranylgeranioyl chains showed significant
      activities. These results suggest that the enzyme dose not recognize ether or
      ester bonds between glycerophosphate and hydrocarbon chains nor the
      stereostructure of the glycerophosphate backbone but mainly targets substrates
      with geranylgeranyl chains.

PMID- 10960478
TI  - Characterization of cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally
      regulated elastase inhibitor.
AB  - We report on the molecular, biochemical, and functional characterization of
      Cucurbita maxima phloem serpin-1 (CmPS-1), a novel 42-kDa serine proteinase
      inhibitor that is developmentally regulated and has anti-elastase properties.
      CmPS-1 was purified to near homogeneity from C. maxima (pumpkin) phloem exudate
      and, based on microsequence analysis, the cDNA encoding CmPS-1 was cloned. The
      association rate constant (k(a)) of phloem-purified and recombinant His(6)-tagged
      CmPS-1 for elastase was 3.5 +/- 1.6 x 10(5) and 2.7 +/- 0.4 x 10(5) m(-)(1) s(
      )(1), respectively. The fraction of complex-forming CmPS-1, X(inh), was estimated
      at 79%. CmPS-1 displayed no detectable inhibitory properties against
      chymotrypsin, trypsin, or thrombin. The elastase cleavage sites within the
      reactive center loop of CmPS-1 were determined to be Val(347)-Gly(348) and
      Val(350)-Ser(351) with a 3:2 molar ratio. In vivo feeding assays conducted with
      the piercing-sucking aphid, Myzus persicae, established a close correlation
      between the developmentally regulated increase in CmPS-1 within the phloem sap
      and the reduced ability of these insects to survive and reproduce on C. maxima.
      However, in vitro feeding experiments, using purified phloem CmPS-1, failed to
      demonstrate a direct effect on aphid survival. Likely roles of this novel phloem
      serpin in defense against insects/pathogens are discussed.

PMID- 10960480
TI  - Catalase-less peroxisomes. Implication in the milder forms of peroxisome
      biogenesis disorder.
AB  - We established a Chinese hamster ovary cell line having a temperature-sensitive
      phenotype in peroxisome biogenesis. This mutant (65TS) was produced by
      transforming a PEX2-defective mutant, Z65, with a mutant PEX2 gene, PEX2(E55K),
      derived from a patient with infantile Refsum disease, a milder form of peroxisome
      biogenesis disorder. In 65TS, catalase was found in the cytosol at a
      nonpermissive temperature (39 degrees C), but upon the shift to a permissive
      temperature (33 degrees C), catalase gradually localized to the structures
      containing a 70-kDa peroxisomal membrane protein, PMP70. In contrast to catalase,
      other matrix proteins containing typical peroxisome targeting signals, acyl-CoA
      oxidase and peroxisomal 3-ketoacyl-CoA thiolase, were co-localized with PMP70 in
      most cells, even at 39 degrees C. We found that these structures are partially
      functional peroxisomes and named them "catalase-less peroxisomes." Catalase-less
      peroxisomes were also observed in human fibroblasts from patients with milder
      forms of peroxisome biogenesis disorder, including the one from which the mutant
      PEX2 gene was derived. We suggest that these structures are the causes of the
      milder phenotypes of the patients. Temperature-dependent restoration of the
      peroxisomes in 65TS occurred even in the presence of cycloheximide, a protein
      synthesis inhibitor. Thus, we conclude that in 65TS, catalase-less peroxisomes
      are the direct precursors of peroxisomes.

PMID- 10960481
TI  - A strategically positioned cation is crucial for efficient catalysis by
      chorismate mutase.
AB  - Combinatorial mutagenesis and in vivo selection experiments previously afforded
      functional variants of the AroH class Bacillus subtilis chorismate mutase lacking
      the otherwise highly conserved active site residue Arg(90). Here, we present a
      detailed kinetic and crystallographic study of several such variants. Removing
      the arginine side chain (R90G and R90A) reduced catalytic efficiency by more than
      5 orders of magnitude. Reintroducing a positive charge to the active site through
      lysine substitutions restored more than a factor of a thousand in k(cat).
      Remarkably, the lysine could be placed at position 90 or at the more remote
      position 88 provided a sterically suitable residue was present at the partner
      site. Crystal structures of the double mutants C88S/R90K and C88K/R90S show that
      the lysine adopts an extended conformation that would place its epsilon-ammonium
      group within hydrogen-bonding distance of the ether oxygen of bound chorismate in
      the transition state. These results provide support for the hypothesis that
      developing negative charge in the highly polarized transition state is stabilized
      electrostatically by a strategically placed cation. The implications of this
      finding for the mechanism of all natural chorismate mutases and for the design of
      artificial catalysts are discussed.

PMID- 10960479
TI  - Mitogen-activated protein kinase plays an essential role in the erythropoietin
      dependent proliferation of CTLL-2 cells.
AB  - Erythropoietin (EPO) and its receptor (EPOR) are required for development of
      erythrocytes. It has been shown that the ectopic expression of EPOR confers EPO
      dependent proliferation on an interleukin 3 (IL3)-dependent cell line, Ba/F3,
      whereas the IL2-dependent T cell line, CTLL-2 expressing the EPOR (T-ER), fails
      to proliferate in response to EPO. However, the molecular basis of the EPO
      unresponsiveness in CTLL-2 has not been clarified. We found that the expression
      level of JAK2 in T-ER cells was much lower than that in Ba/F3 cells. Therefore,
      we examined the effects of forced expression of JAK2 in T-ER cells. In T-ER
      transformants expressing JAK2 (T-JER), EPO induced tyrosine phosphorylation of
      the EPOR, JAK2, and STAT5, and consequently STAT5-responsive genes including bcl
      X and cis1 were normally induced. Furthermore, T-JER cells were resistant to
      apoptosis until at least 72 h after switching from IL2 to EPO. Although T-JER
      cells could not continuously proliferate in the presence of EPO, additional
      expression of JAK2 in T-JER (T-JJER) to a level similar to that in Ba/F3 cells
      supported long term proliferation in response to EPO. JAK2 was equally co
      immunoprecipitated with the EPOR among T-JER, T-JJER, and Ba/F3 cells expressing
      the EPOR (BF-ER). However, EPO-dependent mitogen-activated protein (MAP) kinase
      activation was observed in T-JJER and BF-ER cells but not in T-JER cells. EPO
      dependent long term proliferation of T-JER cells was conferred by expression of
      the constitutively activated form of MEK1. Our results suggest that MAP kinase
      activation is, at least in part, an important component for mitotic signal from
      the EPOR, and CTLL-2 cells probably lack signaling molecule(s) in JAK2 and the
      Ras-MAP kinase pathway.

PMID- 10960482
TI  - Lipoproteins regulate expression of the steroidogenic acute regulatory protein
      (StAR) in mouse adrenocortical cells.
AB  - The steroidogenic acute regulatory protein (StAR) is required for the movement of
      cholesterol from the outer to the inner mitochondrial membrane, the site of
      cholesterol side chain cleavage. Here we describe a novel form of regulation of
      StAR gene expression in steroidogenic cells. Treatment of Y-1 BS1 adrenocortical
      cells with either low density lipoprotein (LDL) or high density lipoprotein (HDL)
      increases expression of endogenous StAR mRNA and protein in a dose-dependent
      manner. Induction of StAR mRNA by lipoprotein requires basal cAMP-dependent
      protein kinase, since the inhibitor, R(p)-8-Br-cAMP, inhibited induction of StAR
      protein by LDL. Likewise, basal StAR expression or LDL induction of StAR protein
      was not detectable in Y-1 kin-8 cells which are deficient in cAMP-dependent
      protein kinase. Aminoglutethimide and ketoconazole were used to determine if side
      chain cleavage of lipoprotein-derived cholesterol is required for induction of
      StAR mRNA. Treatment with either drug alone induced StAR mRNA expression 1.5-3
      fold, while induction of StAR in cells treated with either drug plus LDL, was
      equal to, or greater than, induction seen with either agent alone, suggesting
      that lipoprotein does not regulate StAR via generation of an oxysterol
      intermediate. Both LDL and HDL increased expression of a mouse -966 StAR promoter
      reporter construct 1.5-2.5-fold, indicating that regulation occurs at the level
      of transcription. In contrast, neither lipoprotein was able to induce
      transcription from a -966 StAR promoter in which the steroidogenic factor-1 site
      at -135 was abolished, indicating that regulation of StAR transcription by
      lipoproteins requires steroidogenic factor-1. The regulation of StAR gene
      expression by lipoproteins may represent a positive feedback circuit which links
      cholesterol availability with steroidogenic output.

PMID- 10960488
TI  - Molecular Decoys: Novel Approaches to the Prevention of Hemolytic Uremic
      Syndrome.

PMID- 10960485
TI  - Biochemical and functional characterization of inositol 1,3,4,5, 6
      pentakisphosphate 2-kinases.
AB  - Synthesis of inositol 1,2,3,4,5,6-hexakisphosphate (IP(6)), also known as
      phytate, is integral to cellular function in all eukaryotes. Production of IP(6)
      predominately occurs through phosphorylation of inositol 1,3,4,5,6
      pentakisphosphate (IP(5)) by a 2-kinase. Recent cloning of the gene encoding this
      kinase from Saccharomyces cerevisiae, designated scIpk1, has identified a
      cellular role for IP(6) production in the regulation of mRNA export from the
      nucleus. In this report, we characterize the biochemical and functional
      parameters of recombinant scIpk1. Purified recombinant scIpk1 kinase activity is
      highly selective for IP(5) substrate and exhibits apparent K(m) values of 644 nm
      and 62.8 microm for IP(5) and ATP, respectively. The observed apparent catalytic
      efficiency (k(cat)/K(m)) of scIpk1 is 31,610 s(-)(1) m(-)(1). A sequence
      similarity search was used to identify an IP(5) 2-kinase from the fission yeast
      Schizosaccharomyces pombe. Recombinant spIpk1 has similar substrate selectivity
      and catalytic efficiency to its budding yeast counterpart, despite sharing only
      24% sequence identity. Cells lacking sc-IPK1 are deficient in IP(6) production
      and exhibit lethality in combination with a gle1 mutant allele. Both of these
      phenotypes are complemented by expression of the spIPK1 gene in the sc-ipk1
      cells. Analysis of several inactive mutants and multiple sequence alignment of
      scIpk1, spIpk1, and a putative Candida albicans Ipk1 have identified residues
      involved in catalysis. This includes two conserved motifs: E(i/l/m)KPKWL(t/y) and
      LXMTLRDV(t/g)(l/c)(f/y)I. Our data suggest that the mechanism for IP(6)
      production is conserved across species.

PMID- 10960489
TI  - Pancreatic development and adult diabetes.
AB  - Low birth weight is an important risk factor for type 2 diabetes in later life.
      Maturity-onset diabetes of the young has been linked to genetic sequence
      abnormalities in transcription factors known to be involved in endocrine
      pancreatic development. These observations suggest that both the maternal
      environment and the fetal genome can influence the number and/or function of
      pancreatic beta cells in early life, and that this has life-long implications for
      postnatal diabetes. This article reviews the evidence that suggests that beta
      cells derive from a neogenic process within the pancreatic ductal epithelium,
      controlled by specific transcription factors and locally acting peptide growth
      factors. In rodents, many of the fetal phenotypes of beta cells are destroyed
      during neonatal life in a developmental apoptosis and are replaced by a second
      wave of neogenesis. This results in islets with insulin release characteristics
      suited to postnatal life. The timing and amplitude of these ontological events
      are altered by nutritional sufficiency, and this may be mediated by changes in
      pancreatic growth factor expression, particularly of the IGF axis. Because beta
      cell plasticity after the perinatal period is limited, a dysfunctional
      programming of beta-cell ontogeny may present a long-term risk factor for glucose
      intolerance and type 2 diabetes. This critical window of pancreatic development
      is likely to occur in third trimester of human development.

PMID- 10960483
TI  - Functional synergism between the most common polymorphism in human
      alanine:glyoxylate aminotransferase and four of the most common disease-causing
      mutations.
AB  - The autosomal recessive disorder primary hyperoxaluria type 1 (PH1) is caused by
      a deficiency of the liver-specific pyridoxal-phosphate-dependent enzyme
      alanine:glyoxylate aminotransferase (AGT). Numerous mutations and polymorphisms
      in the gene encoding AGT have been identified, but in only a few cases has the
      causal relationship between genotype and phenotype actually been demonstrated. In
      this study, we have determined the effects of the most common naturally occurring
      amino acid substitutions (both normal polymorphisms and disease-causing
      mutations) on the properties, especially specific catalytic activity, of purified
      recombinant AGT. The results presented in this paper show the following: 1)
      normal human His-tagged AGT can be expressed at high levels in Escherichia coli
      and purified in a correctly folded, dimerized and catalytically active state; 2)
      presence of the common P11L polymorphism decreases the specific activity of
      purified recombinant AGT by a factor of three; 3) AGTs containing four of the
      most common PH1-specific mutations (G41R, F152I, G170R, and I244T) are all
      soluble and catalytically active in the absence of the P11L polymorphism, but in
      its presence all lead to protein destabilization and aggregation into inclusion
      bodies; 4) naturally occurring and artificial amino acid substitutions that lead
      to peroxisome-to-mitochondrion AGT mistargeting in mammalian cells also lead to
      destabilization and aggregation in E. coli; and 5) the PH1-specific G82E mutation
      abolishes AGT catalytic activity by interfering with cofactor binding, as does
      the artificial K209R mutation at the putative site of cofactor Shiff base
      formation. These results are discussed in the light of the high allelic frequency
      ( approximately 20%) of the P11L polymorphism and its importance in determining
      the phenotypic manifestations of mutations in PH1.

PMID- 10960490
TI  - Prolonged survival in hereditary surfactant protein B (SP-B) deficiency
      associated with a novel splicing mutation.
AB  - Hereditary surfactant protein B (SP-B) deficiency has been lethal in the first
      year of life without lung transplantation. We tested the hypothesis that SP-B
      gene mutations may result in milder phenotypes by investigating the mechanisms
      for lung disease in two children with less severe symptoms than have been
      previously observed in SP-B deficiency. Immunostaining patterns for pulmonary
      surfactant proteins were consistent with SP-B deficiency in both children. DNA
      sequence analysis indicated that both children were homozygous for a mutation in
      exon 5 that created an alternative splice site. Reverse transcriptase PCR and
      sequence analysis confirmed use of this splice site, which resulted in a
      frameshift and a premature termination codon in exon 7. The predominant reverse
      transcriptase PCR product, however, lacked exon 7, which restored the reading
      frame but would not allow translation of the exons that encode mature SP-B.
      Western blot analysis detected reduced amounts of mature SP-B as well as an
      aberrant SP-B proprotein that corresponded to the size expected from translation
      of the abnormal transcript. We conclude that a novel splicing mutation was the
      cause of lung disease in these children and that hereditary SP-B deficiency can
      be the cause of lung disease in older children.

PMID- 10960491
TI  - Surfactant modulates intracellular signaling of the adhesion receptor L-selectin.
AB  - Intraalveolar leukocyte accumulation is one of the hallmarks during respiratory
      distress. In the intraalveolar space, leukocyte activation is mediated by
      pathogens, cytokines, and different ligands binding to adhesion molecules.
      Leukocyte stimulation via the adhesion molecule L-selectin is specifically
      induced by ligands expressed on leukocytes, platelets, endothelial cells, or
      lipopolysaccharide. Recently, we have demonstrated that leukocyte activation by L
      selectin transmits several intracellular signaling cascades resulting in capping
      and cytoskeletal changes, the activation of kinases and neutral sphingomyelinase,
      the recruitment of adaptor proteins to the cell membrane, the activation of the
      small G-proteins Ras and Rac, and the release of oxygen. In the present study, we
      examined the effects of surfactant on L-selectin-induced signal transduction in
      leukocytes. Using fluorescence microscopy, we provide evidence that preincubation
      of leukocytes with surfactant significantly inhibits receptor capping; 28+/-7% of
      cells show capping after L-selectin stimulation versus 8+/-5% and 3+/-1% of cells
      after preincubation with Exosurf and Curosurf, respectively (p < 0.05). The
      activity of the neutral sphingomyelinase in cell lysates is also modulated by
      surfactant. In addition, we show that the activation of the tyrosine kinase
      p56lck is diminished by approximately 50% after surfactant treatment. This
      results in inhibition in tyrosine phosphorylation of certain intracellular
      proteins. The interaction of the L-selectin molecule with its antibody was not
      influenced by surfactant as shown by flow cytometry. Surfactant inhibits
      intracellular signaling events of the L-selectin receptor in leukocytes and might
      therefore contribute to the modulatory effects of surfactant on immune function.

PMID- 10960492
TI  - Endothelin-1 and O2-mediated pulmonary hypertension in neonatal rats: a role for
      products of lipid peroxidation.
AB  - We hypothesized that reactive O2 species, or their intermediary products,
      generated during exposure to elevated O2 lead to pathologic endothelin-1
      expression in the newborn lung. Endothelin-1 expression and 8-isoprostane content
      (an in vivo marker of lipid peroxidation) were examined and found to be elevated
      (p < 0.05) in the lungs of newborn rats with abnormal lung morphology and
      pulmonary hypertension, as assessed by right ventricular hypertrophy, after a 14
      d exposure to 60% O2. The antioxidant and lipid hydroperoxide scavenger, U74389G
      (10 mg/kg), given by daily i.p. injection prevented O2-dependent right
      ventricular hypertrophy (p < 0.05 compared with vehicle-treated controls), but
      had no effect on abnormal lung morphology. Additionally, we observed that 8
      isoprostane caused marked endothelin-1 mRNA up-regulation in vitro in primary rat
      fetal lung cell cultures. We conclude that reactive O2 species, or their
      bioactive intermediaries, are causative in O2-mediated pulmonary hypertension and
      endothelin-1 up-regulation. It is likely that the bioactive lipid peroxidation
      product, 8-isoprostane, plays a key role in pathologic endothelin-1 expression
      and pulmonary hypertension during oxidant stress.

PMID- 10960493
TI  - Interleukin-8 expression by fetal and neonatal pulmonary cells in hyaline
      membrane disease and amniotic infection.
AB  - IL-8, a chemokine with striking neutrophil-activating properties, is important in
      the pathogenesis of various disorders of the adult lung. Little is known about
      its production and possible role in fetal and neonatal lung disorders. We
      therefore examined IL-8 expression by immunohistochemistry in lung tissue from
      neonates with hyaline membrane disease, from fetuses with amniotic infection, and
      from a fetal control group with noninflammatory diseases. In the majority of
      cases with hyaline membrane disease, intense IL-8 immunoreaction was seen in
      fetal and neonatal neutrophils and in almost half of these cases, in epithelial
      cells of the terminal airways as well as in the connective tissue cell
      compartment. In contrast, in the amniotic infection group, strong IL-8
      immunostaining was almost exclusively seen in maternal aspirated neutrophils.
      Little or no IL-8 signal was seen in the control cases in all cell types
      examined. Also, no IL-8 production by fetal lung cells was detected in fetuses
      <18 wk of gestation. The marked presence of IL-8 in all cell types of the lung in
      hyaline membrane disease cases indicates a role for IL-8 in the pathobiology of
      hyaline membrane disease possibly similar to that in adult respiratory distress
      syndrome. It further suggests that the cytokine network of the fetal lung is
      already well developed by the second trimester of pregnancy.

PMID- 10960495
TI  - A missense mutation in the mitochondrial cytochrome b gene in a revisited case
      with histiocytoid cardiomyopathy.
AB  - We describe a pathogenic mutation in the mitochondrial cytochrome b gene in a
      patient with a multisystem disorder presenting as histiocytoid cardiomyopathy in
      whom a defect of ubiquinol cytochrome c oxidoreductase of the electron transport
      chain had been documented biochemically. The mutation, a G to A transition at
      nucleotide 15498, results in the substitution of glycine with aspartic acid at
      amino acid position 251. The mutation, which is heteroplasmic and fulfills all
      accepted criteria for pathogenicity, is likely to impair the function of the
      holoenzyme as deduced from its effects on the crystal structure of ubiquinol
      cytochrome c oxidoreductase. This is the first molecular defect associated with
      histiocytoid cardiomyopathy.

PMID- 10960494
TI  - Preventing endotoxin-stimulated alveolar macrophages from decreasing epithelium
      Na+ channel (ENaC) mRNA levels and activity.
AB  - The acute respiratory distress syndrome is characterized by impairment of the
      alveolar-capillary barrier. Our laboratory has shown that distal lung epithelial
      cell (DLEC) amiloride-sensitive Na+ transport is impaired by in vitro coculture
      with endotoxin (lipopolysaccharide)-stimulated alveolar macrophages (AM) through
      an L-arginine-dependent mechanism. To investigate the effect of this model on
      mRNA levels of the rat epithelial Na+ channel, mature fetal rat DLEC monolayers
      were incubated for 16 h with rat AM (1 x 10(7)) and lipopolysaccharide (10
      microg/mL), or the cell-free supernatant of lipopolysaccharide-stimulated rat AM.
      Such exposure resulted in a profound decrease in mRNA expression for all subunits
      (alpha, beta, and gamma) of the rat epithelial Na+ channel, without affecting 18S
      RNA levels. This effect was prevented by the antioxidant N-acetylcysteine. In
      separate experiments, confluent DLEC monolayers were exposed to
      lipopolysaccharide-stimulated AM supernatant for 16 h with or without N
      acetylcysteine and DTT and studied in Ussing chambers. As previously demonstrated
      in our laboratory, AM supernatant resulted in a significant (p < 0.05) impairment
      of DLEC Na+ transport, as reflected by a decrease in the amiloride-sensitive
      component of short-circuit current (control, 3.96 +/- 0.18 microA/cm2 versus
      supernatant, 2.34 +/- 0.56 microA/cm2; p < 0.05). This effect was significantly
      reversed by N-acetylcysteine (3.55 +/- 0.48 microA/cm2), but not by DTT (1.87 +/-
      0.21 microA/cm2). N-acetylcysteine, but not DTT, increased DLEC thiol levels.
      These studies elucidate mechanisms by which activated AM impair alveolar
      epithelial barrier function in an in vitro model of acute lung injury.

PMID- 10960496
TI  - Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of
      patients, genetically, and biochemically distinct.
AB  - Glutaryl-CoA dehydrogenase (GCDH) deficiency causes glutaric aciduria type I (GA
      I), an inborn error of metabolism that is characterized clinically by dystonia
      and dyskinesia and pathologically by neural degeneration of the caudate and
      putamen. Studies of metabolite excretion allowed us to categorize 43 GA I Spanish
      patients into two groups: group 1 (26 patients), those presenting with high
      excretion of both glutarate and 3-hydroxyglutarate, and group 2 (17 patients),
      those who might not be detected by routine urine organic acid analysis because
      glutarate might be normal and 3-hydroxyglutarate only slightly higher than
      controls. Single-strand conformation polymorphism (SSCP) screening and sequence
      analysis of the 11 exons and the corresponding intron boundaries of the GCDH gene
      allowed us to identify 13 novel and 10 previously described mutations. The most
      frequent mutations in group 1 were A293T and R402W with an allele frequency of
      30% and 28%, respectively. These two mutations were also found in group 2, but
      always in heterozygosity, in particular in combination with mutations V400M or
      R227P. Interestingly, mutations V400M and R227P were only found in group 2, and
      at least one of these mutations was found in 11 of 15 unrelated alleles,
      accounting together for 53% of the mutant alleles in group 2. Therefore, it seems
      clear that two genetically and biochemically distinct groups of patients exist.
      The severity of the clinical phenotype seems to be closely linked to the
      development of encephalopathic crises rather than to residual enzyme activity or
      genotype. Comparison of GCDH protein with other acyl-CoA dehydrogenases (whose x
      ray crystal structure has been determined) reveals that most of the mutations
      identified in GCDH protein seem to affect folding and tetramerization, as has
      been described for a number of mutations affecting mitochondrial beta-oxidation
      acyl-CoA dehydrogenases.

PMID- 10960497
TI  - Galactose breath testing distinguishes variant and severe galactose-1-phosphate
      uridyltransferase genotypes.
AB  - A galactose breath test that quantitates [1-(13)C]galactose conversion to 13CO2
      provides information on the whole body galactose oxidative capacity. As there is
      little information on the relationship between whole body oxidation and the
      genotype in patients with galactosemia, we measured the 13CO2 excretion for 2 h
      after administration of [1-(13)C]galactose in 37 patients (3-48 y old) with
      galactose-1-phosphate uridyltransferase (GALT) deficiency and 20 control subjects
      (3-37 y old). Eleven patients with the common Q188R/Q188R genotype and no
      detectable erythrocyte GALT activity eliminated <2% of a bolus of [1
      (13)C]galactose as 13CO2 compared with 8.47 to 28.23% in controls. This defines a
      severe metabolic phenotype. Seven patients with one Q188R allele and a second
      mutant allele such as L195P, E308K, V151A, M142K, or Q344K and one patient with a
      K285N/unknown genotype also released <2% as 13CO2 in 2 h. The presence of N314D
      or S135L as the second mutant allele does not impair total body galactose
      oxidation, as individuals with the GALT genotype of Q188R/N314D, K285N/N314D, and
      Q188R/S135L had normal 2-h galactose breath tests. Subjects with S135L/S135L,
      N314D/N314D, S135L/deltaT2359 as well as other rarer genotypes such as
      R258C/Y209C, E203K/IVSC-N314D, K285N/T138M, Q188R/D113N, S135L/F171S,
      R148W/N314D, and IVSC-N314D/N314D oxidized galactose comparable to controls. The
      dissociation of residual erythrocyte GALT activity and whole body galactose
      oxidative capacity is exemplified by blacks with a S135L/S135L genotype and
      absent erythrocyte GALT activity. An oral 2-h [1-(13)C]galactose breath test
      distinguishes severe and variant GALT genotypes and enables delineation of the
      extent of impaired galactose metabolism in an array of patients who possess
      diverse GALT mutations. It may prove to be useful in establishing whether a
      patient is capable of manifesting disease similar to patients with a Q188R/Q188R
      genotype.

PMID- 10960498
TI  - Glucose-6-phosphatase mutation G188R confers an atypical glycogen storage disease
      type 1b phenotype.
AB  - Glycogen storage disease type 1a (GSD 1a) is caused by a deficiency in microsomal
      glucose-6-phosphatase (G6Pase). A variant (GSD 1b) is caused by a defect in the
      transport of glucose-6-phosphate (G6P) into the microsome and is associated with
      chronic neutropenia and neutrophil dysfunction. Mutually exclusive mutations in
      the G6Pase gene and the G6P transport gene establish GSD la and GSD 1b as
      independent molecular processes and are consistent with a multicomponent
      translocase catalytic model. A modified translocase/catalytic unit model based on
      biochemical data in a G6Pase knockout mouse has also been proposed for G6Pase
      catalysis. This model suggests coupling of G6Pase activity and G6P transport. A 5
      mo-old girl with hypoglycemia, hepatomegaly, and lactic acidemia was diagnosed
      with GSD 1a. She also developed neutropenia, neutrophil dysfunction, and
      recurrent infections characteristic of GSD 1b. Homozygous G188R mutations of the
      G6Pase gene were identified, but no mutations in the G6P translocase gene were
      found. We have subsequently identified a sibling and two unrelated patients with
      similar genotypic/phenotypic characteristics. The unusual association of
      neutrophil abnormalities in patients with homozygous G188R mutations in the
      G6Pase gene supports a modified translocase/catalytic unit model.

PMID- 10960499
TI  - Identification of a new form of AQP4 mRNA that is developmentally expressed in
      mouse brain.
AB  - The water channel aquaporin 4 (AQP4) is abundantly expressed in the brain, and
      also in lung and kidney. Previous studies have suggested that there are at least
      two AQP4 mRNA. The two mRNA encode for two AQP4 proteins that differ with regard
      to the length of the N-terminal: AQP4.M1 and AQP4.M23. Here we report, by use of
      reverse transcriptase PCR and comparison of genomic and cDNA structures, the
      presence of a third form of mouse AQP4 mRNA. The upstream sequence of this form
      of mRNA originates from an additional exon, interspaced between exon 0 and exon
      1, and an alternatively spliced form of exon 1. Analysis of nucleotide sequence
      suggests that this new form of AQP4 mRNA also encodes for the AQP4.M23 protein.
      The two forms of AQP4 mRNA that presumably both encode for M23 have a tissue- and
      age-specific expression. The new AQP4 mRNA was predominantly expressed in brain.
      The expression was approximately twofold higher in the adult brain than in the
      infant brain. In contrast, the expression levels of the new mRNA were low in both
      infant and adult lung and kidney. The previously described mRNA encoding for
      AQP4.M23 was predominantly expressed in lung and kidney. In lung, the expression
      of this form was higher in infancy than in adulthood. In conclusion, we have
      identified a new form of AQP4 mRNA that is predominantly expressed in the brain
      and that is developmentally regulated.

PMID- 10960500
TI  - Real-time spectral analysis of the fetal EEG: a new approach to monitoring sleep
      states and fetal condition during labor.
AB  - Adverse perinatal events affecting cerebral functions are a major cause of
      neonatal mortality, morbidity, and long-term neurologic deficit. Intrapartum
      fetal EEG, which records fetal brain electrical activity, provides a monitoring
      modality for evaluating the fetal CNS during labor. In this study, we describe a
      new approach to such monitoring that is based on real-time spectral analysis of
      the fetal EEG during labor. Fourteen pregnant women with uncomplicated term
      pregnancies who went into labor participated in the study. Two suction-cup
      electrodes were applied to the fetal scalp at the occipitoparietal or parietal
      region after rupture of membranes. Real-time spectral analysis was used to
      determine the frequency and amplitude of the fetal EEG signal. The spectral edge
      frequency (SEF) was calculated as the frequency below which 90% of the power in
      the power spectrum resides. The average EEG amplitude and the SEF were displayed
      using the density spectral array technique. Fetal heart rate and intrauterine
      pressure were also measured. Two fundamental EEG patterns were identified: high
      voltage slow activity and low-voltage fast activity. The SEF was found to be an
      excellent index of cyclic EEG activity. Fetal heart rate demonstrated increased
      variability and an elevated baseline during low-voltage fast activity, whereas
      both parameters decreased during high-voltage slow activity. During episodes of
      variable decelerations in the fetal heart rate, a decrease in the SEF was
      observed, accompanied by an increased EEG voltage. The results obtained
      substantiate the presence of sleep cycles in the human fetus. This kind of
      cortical activity monitoring may enable rapid alertness to cerebral hypoxia and
      allow for prompt intervention, thereby decreasing the risk for birth asphyxia and
      subsequent brain damage.

PMID- 10960501
TI  - Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn
      piglet does not protect against cerebral damage.
AB  - Transient perinatal hypoxia-ischemia (HI) can lead to delayed cerebral damage
      beginning 8-24 h after resuscitation. Cerebroprotective therapies applied soon
      after HI may thus reduce the severity of brain injury. We have previously shown
      that MgSO4 administration to newborn piglets after HI fails to prevent the
      delayed global impairment in cerebral energy metabolism characteristic of severe
      brain damage. However, high extracellular concentrations of magnesium ions have
      been found to prevent specific excitotoxic neural cell death in vivo and in
      vitro. This study therefore examined the hypothesis that MgSO4 administration
      after HI reduces damage in some regions of the brain even though global energy
      metabolism is unaffected. Twelve newborn piglets were subjected to global
      cerebral HI by transient occlusion of both common carotid arteries and reduction
      of the inspired oxygen fraction to 0.12 until cerebral high-energy phosphates,
      measured by magnetic resonance spectroscopy, were significantly depleted.
      Subjects were randomly assigned to two groups of six: the first received MgSO4
      (three doses, 400 mg/kg 1 h after resuscitation and 200 mg/kg at 12 and 24 h),
      and the second received placebo infusions. At 48 h after the start of the
      experiment, the piglets were killed and their brains were perfused, fixed, and
      embedded in paraffin wax. Five-micrometer sections were stained with hematoxylin
      and eosin to allow semiquantitative analysis of the severity and extent of injury
      to the hippocampus, cerebellum, cerebral cortex, caudate nucleus, thalamus, and
      striatum and the white matter tracts. There was no difference in the severity of
      tissue damage between the MgSO4-treated group and the placebo-treated animals in
      any brain region.

PMID- 10960502
TI  - Numerical modeling of temperature distributions within the neonatal head.
AB  - Introduction of hypothermia therapy as a neuroprotection therapy after hypoxia
      ischemia in newborn infants requires appraisal of cooling methods. In this
      numerical study thermal simulations were performed to test the hypothesis that
      cooling of the surface of the cranium by the application of a cooling bonnet
      significantly reduces deep brain temperature and produces a temperature
      differential between the deep brain and the body core. A realistic three
      dimensional (3-D) computer model of infant head anatomy was used, derived from
      magnetic resonance data from a newborn infant. Temperature distributions were
      calculated using the Pennes heatsink model. The cooling bonnet was at a constant
      temperature of 10 degrees C. When modeling head cooling only, a constant body
      core temperature of 37 degrees C was imposed. The computed result showed no
      significant cooling of the deep brain regions, only the very superficial regions
      of the brain are cooled to temperatures of 33-34 degrees C. Poor efficacy of head
      cooling was still found after a considerable increase in the modeled thermal
      conductivities of the skin and skull, or after a decrease in perfusion. The
      results for the heatsink thermal model of the infant head were confirmed by
      comparison of results computed for a scaled down adult head, using both the
      heatsink description and a discrete vessel thermal model with both anatomy and
      vasculature obtained from MR data. The results indicate that significant
      reduction in brain temperature will only be achieved if the infant's core
      temperature is lowered.

PMID- 10960504
TI  - Factors affecting heart rate variability and heart rate responses to tilting in
      infants aged 1 and 3 months.
AB  - Heart rate variability (HRV) and heart rate (HR) responses following a 60 degree
      head-up tilt were measured in 60 infants at 1 and 3 mo of age to investigate the
      effects on these of age, sleep state, sleep position, and mother's smoking
      status. HRV was determined from Poincare plots of 500 sequential RR intervals to
      measure overall variability derived from the SDRR of this plot, and instantaneous
      variability derived from the SDdeltaRR. HR responses to the tilt were measured as
      changes in RR interval length from rest to immediately following the tilt and
      again once a stable pattern was reached. SDRR and SDdeltaRR increased 20 and 40%,
      respectively, with age (p < 0.0001), SDRR was higher in active sleep (AS) than
      quiet sleep (QS, +72%, p < 0.0001) but both measures of variability (SDRR and
      SDdeltaRR) were lower in the prone position compared with supine (-18%, p <
      0.0001). However, several findings were dependent on the basal RR interval, thus
      the age effect disappeared once RR interval was taken into account, sleep state
      remained an important factor and the lower variability when prone now became a
      difference of -3% (p = 0.034). The tilt generally provoked a reflex tachycardia
      followed by a bradycardia and settling to a stable HR level below, at, or above
      baseline within 30 s. The more unusual responses were no HR change, sustained
      tachycardia or sustained bradycardia (15% of total). These were more likely to
      occur in younger infants (p = 0.008) and in AS (p < 0.0001). No changes were seen
      in any of the cardiac indices related to maternal smoking status. The findings
      confirm several reports indicating that prone sleeping damps some physiologic
      responses. The data emphasize the need to consider basal heart rate, and sleep
      position as well as sleep state in autonomic function testing during infant
      sleep.

PMID- 10960503
TI  - Effect of pantothenic acid on hippurate formation in sodium benzoate-treated
      HepG2 cells.
AB  - Inborn errors of urea synthesis result in hyperammonemia. Sodium benzoate (SB)
      therapy has been beneficial in the treatment of hyperammonemia. It conjugates
      with glycine to form hippurate, which is then excreted. SB has also been used to
      treat children with nonketotic hyperglycinemia (NKH), where glycine is removed,
      on conjugation, as hippurate. In mammalian liver mitochondria, SB is activated by
      an ATP-dependent reaction to its CoA ester, before conjugation with glycine.
      Pantothenic acid (PA) is the precursor of CoA. In this investigation, increasing
      the amounts of PA increased CoA levels in HepG2 cells. It also significantly
      increased formation of hippurate in SB-treated cells. These findings suggest a
      beneficial effect of PA on the SB therapy in children with NKH as well as
      hyperammonemia.

PMID- 10960505
TI  - Effect of granulocyte and granulocyte macrophage colony stimulating factors (G
      CSF and GM-CSF) on neonatal neutrophil functions.
AB  - Although there are many studies on the effect of granulocyte and granulocyte
      macrophage colony stimulating factors (G/GM-CSF) on adult neutrophil functions,
      there is little information regarding their influence on neonatal cells. We
      studied the in vitro effect of G/GM-CSF on neutrophil chemotaxis, polarization,
      and superoxide anion generation in 47 neonates compared with 35 adults. We found
      that G-CSF and GM-CSF significantly enhanced the chemotaxis of newborn infants'
      neutrophils, normalizing their chemotactic defect [from 35 +/- 7 cells/field
      (mean +/- SE) to 49 +/- 5 cells/field with G-CSF, p < 0.05 and to 55 +/- 4
      cells/field with GM-CSF, p < 0.001]. It is notable that the maximal neutrophil
      response to the cytokines was observed particularly in the newborn infants with
      severe impairment in their chemotactic activity. Statistical analysis of the data
      showed a significant inverse correlation, which supported this observation (r = 
      0.6, p < 0.02 for G-CSF; r = -0.76, p < 0.001 for GM-CSF). The reduced
      polarization of neonatal compared with adult cells [71 +/- 5% versus 86 +/- 2%
      (mean +/- SE), p < 0.05], was corrected by CSF-priming (to 87 +/- 4% with G-CSF
      and to 92 +/- 2% with GM-CSF, p < 0.05). In addition, the neutrophil superoxide
      generation was significantly improved in both groups following the CSF-priming.
      GM-CSF and G-CSF gave comparable results in all functions studied except that GM
      CSF improved superoxide release to a greater extent. This study shows a
      significant improvement of the neonatal neutrophil functions following in vitro
      CSF-priming and contributes to a better understanding of the neonatal neutrophil
      behavior when treated with G/GM-CSF.

PMID- 10960506
TI  - Ethnicity and environment may affect the phenotype of immune thrombocytopenic
      purpura in children.
AB  - Little is known about the influence of environmental and ethnic factors on the
      epidemiology of immune thrombocytopenic purpura (ITP). Therefore we compared the
      initial presentation and condition after 6 mo in 90 Vietnamese and 89 German and
      Swiss children with newly diagnosed ITP. Data from the two cohorts were collected
      within the same time period. No differences in age and sex were observed between
      the Asian and European cohorts, but significant differences between initial
      platelet count, the occurrence of dry versus wet bleeding symptoms, and infection
      preceding the onset of ITP were found. Children who had chronic ITP also differed
      with respect to platelet count and postinfectious state, but not initial bleeding
      type. In addition, chronic ITP occurred more often than expected with a male to
      female ratio of 1.2 in Vietnam and 2 in Germany and Switzerland. The data support
      the potential influence of environmental or ethnic factors on the different
      aspects of ITP, and point to the need for further epidemiologic investigations.

PMID- 10960507
TI  - Leptin reduces body weight gain in neonatal rats.
AB  - Leptin (OB protein) elicits a neuroendocrine response to starvation and states of
      nutritional abundance to stabilize the proportion of body fat. Leptin has
      dramatic effects on food intake and energy expenditure in adult and juvenile
      rodents. However, whether the neonatal period is associated with the development
      of an effective leptin feedback system is still not known. In this study, we
      evaluated the effects of peripherally administered leptin on body weight changes
      in neonatal rats during the early suckling period (from birth to 10 d). Our
      results show that daily i.p. injections of leptin (0.3 microg/g and 1.0 microg/g)
      to neonatal rats led to a significant reduction in weight gain over 10 d compared
      with the control group (p < 0.01 and p < 0.01, respectively). Concomitant with a
      reduction in weight gain, retroperitoneal fat pad weight also significantly
      decreased in the leptin-treated group. Our data indicate that the potential for
      energy balance regulation by leptin occurs in the first day after birth. In
      addition, we also observed that 3 d after discontinuing leptin treatment, the
      body weight as well as the fat pad weight of leptin-treated pups returned to the
      control level. Our results demonstrate that leptin reduces body weight gain in
      neonatal rats.

PMID- 10960508
TI  - Pubertal adolescent male-female differences in insulin sensitivity and glucose
      effectiveness determined by the one compartment minimal model.
AB  - Most studies of insulin sensitivity in puberty have been cross-sectional and have
      not been able to longitudinally address changes that might occur. In addition,
      these studies were unable to separate out glucose's ability to stimulate its own
      disposal (glucose effectiveness, S(G)) from insulin sensitivity (S(I)) or to
      separate the hepatic and peripheral effects of insulin. To address these
      problems, we used the frequently sampled i.v. glucose tolerance test with [6,6]D2
      glucose to study S(G)* and S(I)* in 24 children (Tanner stage 1-3) at 6-mo
      intervals over an 18-mo period. Mean overnight GH and fasting GH binding protein
      (GHBP), IGF-1, and leptin levels were also measured. S(G)* did not differ between
      the sexes or Tanner stages. S(I)* did not differ between Tanner stages for either
      sex and was higher in boys than in girls. Hepatic insulin resistance did not
      differ between sexes or Tanner stages. S(G)* was not related to any of the other
      variables measured. S(I)* was negatively related to BMI, GHBP, IGF1, and leptin.
      These results demonstrate that insulin sensitivity is greater in prepubertal and
      early pubertal boys than in girls and is primarily determined by body mass
      effects.

PMID- 10960509
TI  - Ontogeny of fibroblast growth factors in the early development of the rat
      endocrine pancreas.
AB  - Pancreatic islet ontogeny involves endocrine cell neogenesis from ductal
      epithelium and islet expansion by cell replication, balanced by apoptotic
      deletion of endocrine cells which, in rat, is pronounced in the neonate.
      Fibroblast growth factors (FGF) are involved in tissue morphogenesis, and we
      examined the distribution and ontogeny of several FGF within rat pancreas from
      late fetal life until weaning. Islet cell replication (immunohistochemistry for
      proliferating cell nuclear antigen) did not change, but a transient increase in
      ductal epithelial cell replication existed between postnatal days (pnd) 10 and
      14. Immunoreactive FGF-1 was found mainly in alpha cells of islets, and FGF-2
      immunoreactivity and mRNA throughout the islets, their distribution increasing
      with age. Both FGF-1 and -2 were also located in ductal epithelium, being
      maximally distributed at pnd 10-14, coincident with increased cell replication,
      and when mRNA transcripts encoding FGF-1 (4.4 kb) and FGF-2 (7 kb) were
      relatively increased in pancreata. FGF-4 and -6 immunoreactivities were localized
      strongly within islets and ductal cells. In contrast, immunoreactive FGF-7 was
      associated with pancreatic mesenchyme and intra-and extraislet endothelial cells,
      and mRNA abundance was transiently increased between pnd 4 and 12, suggesting a
      role in the initiation of endocrine cell neogenesis. Exogenous FGF-7 was fivefold
      more potent than FGF-1 or -2 in stimulating DNA synthesis within isolated rat
      islets. Multiple FGF are expressed within defined compartments of developing
      pancreas and may contribute to endocrine cell neogenesis and islet function.

PMID- 10960510
TI  - Direct evidence for transplacental allergen transfer.
AB  - Allergies are increasing, and despite deeper insights into the immunologic basis
      of these diseases, preventive measures are not yet efficient. As the induction of
      allergic diseases is often triggered in early childhood, perinatal or prenatal
      preventive strategies would be beneficial. We investigated the transfer of
      inhalant and nutritive allergens across the human placenta. For this purpose, the
      maternal side of a placental cotyledon was perfused in vitro with an allergen
      containing medium, and a specific ELISA was used to detect the allergens on the
      fetal side. Both allergens evaluated, birch pollen major allergen Bet v1 and the
      milk allergen beta-lactoglobulin, could be shown to cross the placenta. The
      nutritive allergen beta-lactoglobulin was not only transferred across the
      placenta in all eight experiments, but was also detectable within the first
      minutes of perfusion. The peak allergen concentration on the fetal side could be
      increased by addition of human immunoglobulin. For the inhalant allergen Bet v1,
      transfer was observed in two of 10 placental experiments, and only if human
      immunoglobulin was added. A pulsatility wave with a frequency of 30-35 min
      suggested an active transfer mechanism. We conclude that allergens are actively
      and selectively transferred across the placenta. Therefore, controlled maternal
      allergen exposure might offer new ways to induce tolerance to specific allergens
      in the fetus.

PMID- 10960511
TI  - Clinical diagnosis of pneumothorax is late: use of trend data and decision
      support might allow preclinical detection.
AB  - Pneumothorax in the newborn has a significant mortality and morbidity. Early
      diagnosis would be likely to improve the outlook. Forty-two consecutive cases of
      pneumothorax that developed after admission to a tertiary referral neonatal
      medical intensive care unit over 4 y from 1993 to 1996 were reviewed. The time of
      onset of the pneumothorax was determined by retrospective evaluation of the
      computerized trend of transcutaneous carbon dioxide (tcpCO2) and oxygen tensions.
      The timing of the occurrence in the notes and x-rays determined the time of
      clinical diagnosis noted at the time. The difference was the time the condition
      was undiagnosed. The overall mortality before discharge was 45% (19 cases), four
      patients succumbing within 2 h. The median time (range) between onset of
      pneumothorax and clinical diagnosis was 127 min (45-660 min). In most cases, the
      endotracheal tube was aspirated and the transcutaneous blood gas sensor was
      repositioned, and in at least 40% of the cases, the baby was reintubated before
      the diagnosis was made. Reference centiles were constructed for level of tcpCO2
      and slope of the trended tcpCO2 over various time intervals (in minutes) from 729
      infants from 23 to 42 wk gestation who needed intensive care during the first 7 d
      of life from the same time period. The 5-min tcpCO2 trend slopes were compared in
      index and matched control infants. The presence of five consecutive and
      overlapping 5-min slopes greater than the 90th centile showed good discrimination
      for a pneumothorax (area under the receiver operating characteristic curve, 89%).
      We concluded that 1) the clinical diagnosis of pneumothorax was late, occurring
      when infants decompensate; 2) trend monitoring of tcpCO2 might allow the
      diagnosis to be made earlier if used properly; and 3) use of reference centiles
      of the trended slopes of tcpCO2 might be used for automatic decision support in
      the future.

PMID- 10960512
TI  - Back to the future in RBC preservation.

PMID- 10960513
TI  - Complications of plasma exchange in 71 consecutive patients treated for
      clinically suspected thrombotic thrombocytopenic purpura-hemolytic-uremic
      syndrome.
AB  - BACKGROUND: With the increased frequency of diagnosis and improved survival of
      thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome (TTP-HUS), the
      morbidity of plasma exchange (PE) treatment has become more important. STUDY
      DESIGN AND METHODS: Data were prospectively collected on 71 consecutive patients
      referred to the Oklahoma Blood Institute (OBI) for PE treatment for clinically
      suspected TTP-HUS from mid-1996 to mid-1999. Complications were defined as major
      or minor, and distinguished between those related to central venous catheter
      access or to the plasma. RESULTS: Twenty-one patients (30%) had 27 major
      complications, which caused two deaths. The major complications included 2
      episodes of hemorrhage after subclavian line insertion (1 death), 1 pneumothorax
      requiring a chest tube, 12 systemic infections (1 death), 7 episodes of catheter
      thrombosis requiring removal of the central venous catheter, 2 episodes of venous
      thrombosis requiring anticoagulant treatment, 2 episodes of hypoxemia and
      hypotension, and 1 episode of serum sickness. Minor complications occurred in 22
      additional patients (31%). Twenty-eight patients (39%) had no complications.
      CONCLUSIONS: The morbidity and mortality of catheter placement and PE are
      important considerations when PE treatment for clinically suspected TTP-HUS is
      anticipated.

PMID- 10960514
TI  - Acute intravascular hemolysis secondaryto out-of-group platelet transfusion.
AB  - BACKGROUND: Acute intravascular hemolysis is rarely associated with platelet
      transfusion. Out-of-group single-donor platelets may cause hemolysis if the donor
      has high-titer ABO hemagglutinins. CASE REPORT: A 44-year-old woman, blood group
      A, was recently diagnosed with acute myeloid leukemia and was receiving
      chemotherapy. After the transfusion of apheresis platelets from a group O donor,
      back pain, hemoglobinuria, and hemoglobinemia developed, and her Hb dropped by
      2.3 g per dL, despite the transfusion of 2 units of RBCs. RESULTS: Investigation
      revealed acute intravascular hemolysis with a positive DAT due to anti-A(1) on
      her RBCs. The donor's titer of anti-A(1) was greater than 16,000. CONCLUSION:
      Review of published cases raises the possibility that hemolytic reactions to out
      of-group platelets may be more frequent since the use of apheresis platelets has
      increased.

PMID- 10960515
TI  - Vaccination-associated immune hemolytic anemia in two children.
AB  - BACKGROUND: Two children in whom acute autoimmune hemolytic anemia (AIHA)
      developed after vaccination were studied. CASE REPORTS: The children were a 20
      month-old girl and a 21-month-old boy. The diagnosis of AIHA was made in
      accordance with established criteria (hemolysis, positive DAT, and lack of other
      reasons for the hemolysis). Serologic tests were performed according to standard
      technique. RESULTS: The girl experienced two attacks of hemolysis. The first
      episode occurred 2 weeks after oral polio vaccination, and the second episode was
      observed 7 months later, when she received a simultaneous vaccination against
      mumps, rubella, and measles. The DAT was strongly positive with anti-C3d. No
      autoantibodies were detectable in either episode. The boy experienced acute
      hemolysis a few days after a simultaneous revaccination against diphtheria
      pertussis-tetanus, Haemophilus influenzae, hepatitis B, and polio. The DAT using
      anti-IgG was strongly positive, and the DAT performed with anti-C3d was weakly
      positive. CONCLUSION: Vaccination-induced AIHA resembles those forms of AIHA
      related to infectious diseases, and it may occur more frequently than has been
      reported.

PMID- 10960516
TI  - Hepatitis B virions isolated with antibodies to the pre-S1 domain reveal occult
      viremia by PCR in Alaska Native HBV carriers who have seroconverted.
AB  - BACKGROUND: Occult viremia occurring before the appearance of HBsAg or after the
      disappearance of HBsAg is detectable by gene amplification technologies whose
      efficiency depends on nucleic acid preparation. STUDY DESIGN AND METHODS: To
      isolate HBV DNA from viremic plasma, immunoaffinity capture (IAC) of intact HBV
      with biotinylated pre-S1 antibodies coupled to streptavidin-coated magnetic beads
      was evaluated. IAC was compared with a silica-gel method (Qiagen [QSG]) and its
      two modifications wherein the samples were heated with lysis buffer at 60(o)C for
      10 minutes (QSG-60) or at 58 degrees C for 60 minutes with proteinase-K (QSG-PK).
      Each HBV DNA sample was tested by heminested PCR amplification of the HBV gene
      sequences. A total of 36 coded serum samples were tested, including three HBsAg
      positive controls and 33 former chronic HBV carriers who had seroconverted
      (developed antibody to HBsAg [anti-HBs]). Commercially available seroconversion
      panels (PHM 907, 911, and 922) were similarly tested for window-period viremia.
      RESULTS: In the 33 former chronic HBV carriers who had seroconverted, IAC
      revealed HBV DNA in 17 samples, whereas it was revealed in only 11 samples by QSG
      PK (p = 0.031), 10 by QSG-60 (p = 0.016), and 9 by QSG (p = 0.0078). However, HBV
      DNA was not amplified from the 17 samples at 1-in-10 dilutions; thus, they were
      considered to have low-level viremia. IAC revealed HBV DNA as early as or earlier
      than the other methods in PHM 907, 911, and 922 panels. CONCLUSION: IAC is
      apparently an optimal method of sample preparation for amplification of HBV DNA
      in patients in the pre-HBsAg window period, and for detecting low-level viremia
      persistent in several individuals who were former chronic HBV carriers who had
      seroconverted (developed anti-HBs).

PMID- 10960517
TI  - Performance of second- and third-generation RIBAs for confirmation of third
      generation HCV EIA-reactive blood donations. Retrovirus Epidemiology Donor Study.
AB  - BACKGROUND: Licensure of an enhanced HCV screening assay (HCV 3.0 EIA) without
      concurrent licensure of a complementary supplemental assay (i.e., RIBA HCV 3.0
      strip immunoblot assay [RIBA-3]) decoupled screening and supplemental testing. In
      March 1998, the FDA Center for Biologics Evaluation and Research (CBER)
      recommended the use of RIBA-3 on RIBA HCV 2.0 strip immunoblot assay (RIBA-2)
      indeterminate units screened with HCV EIA 3.0. STUDY DESIGN AND METHODS: The
      sensitivity of RIBA-2 and RIBA-3 was compared in tests on HCV 3.0 EIA-repeatably
      reactive (RR) units identified immediately after the implementation of HCV 3.0
      EIA screening. Two protocols were evaluated: parallel testing of HCV 3.0 EIA-RR
      units by RIBA-2 and RIBA-3 and reflex testing of HCV 3.0 EIA-RR and RIBA-3
      confirmed-positive units by RIBA-2. All specimens with discordant RIBA-2 and RIBA
      3 results and a representative sampling with concordant RIBA results were tested
      by PCR. RESULTS: In the parallel testing protocol, 99,777 donations were
      screened, with 245 HCV 3.0 EIA-RR specimens included in the study. Of 166 RIBA-2
      positive samples, 165 tested positive in RIBA-3 (1 sample reacted to the control
      superoxide dismutase antigen in RIBA-3). Thirty-two (74%) of 43 RIBA-2
      indeterminate specimens and 4 (11%) of 36 RIBA-2-negative specimens tested
      positive in RIBA-3. HCV RNA was identified in 5 (16%) of 32 RIBA-2
      indeterminate/RIBA-3-positive donations, as well as in 26 (70%) of 37 concordant
      RIBA-2/RIBA-3-positive donations. In the reflex testing protocol, 292,459
      donations were screened, with 709 HCV 3.0 EIA-RR specimens included in the study.
      RIBA-3 testing yielded 517 (73%) positive specimens, of which 50 (9.7%) tested
      indeterminate and 15 (2.9%) tested negative in RIBA-2. Among the RIBA-discordant
      specimens, 10 (20%) RIBA-2-indeterminate specimens and 1 (7%) RIBA-2-negative
      specimens tested positive in PCR; in comparison, 60 (77%) of 78 concordant RIBA
      2/RIBA-3-positive units tested positive in PCR. CONCLUSIONS: RIBA-3 is
      significantly more sensitive than RIBA-2 in testing of HCV 3.0 EIA-screened
      donations. During the review process of this manuscript, the FDA licensed the
      RIBA-3 test.

PMID- 10960518
TI  - Comparative performances of an HTLV-I/II EIA and other serologic and PCR assays
      on samples from persons at risk for HTLV-II infection.
AB  - BACKGROUND: HTLV-I and HTLV-II are related exogenous pathogenic human
      retroviruses. Until recently, ELISAs based on HTLV-I antigens have been used to
      screen for the presence of HTLV-I or -II antibodies. The HTLV-I-based assays have
      not been as sensitive in detecting antibodies to HTLV-II as in detecting
      antibodies to HTLV-I. The Abbott HTLV-I/HTLV-II ELISA uses a combination of HTLV
      I and HTLV-II antigens to detect antibodies to the whole HTLV group. The
      performance of this ELISA was compared to that of several HTLV-I-based serologic
      assays and an HTLV-II PCR assay in cohorts of South American Indians and New York
      City IV drug users (IVDUs) in whom HTLV-II is endemic. STUDY DESIGN AND METHODS:
      Sera from 429 South American Indians and New York City IVDUs were evaluated for
      HTLV antibodies by the use of three ELISAs (rgp21-enhanced HTLV-I/II, Cambridge
      Biotech; Vironostika HTLV-I/II, Organon Teknika; and HTLV-I/HTLV-II, Abbott), and
      a Western blot (WB) assay. Peripheral blood leukocyte DNA from each person was
      analyzed for HTLV-I and HTLV-II pol DNA via PCR. The HTLV-II PCR-positive samples
      were further subtyped via cloning and sequencing and/or oligomer restriction.
      RESULTS: Two hundred four samples (48%) were positive for HTLV-II by serologic
      and/or PCR assays. All of the positive samples from the Indians and approximately
      one-third of the positive samples from the IVDUs were of the HTLV-IIB subtype.
      Comparative analyses indicate that the sensitivity and specificity of the various
      assays were: PCR, 98 and 100 percent; Abbott HTLV-I/HTLV-II, 78 and 95 percent;
      Cambridge Biotech HTLV-I/II, 76 and 96 percent; Vironostika HTLV-I/II, 71 and 98
      percent; and WB, 73 and 100 percent, respectively. CONCLUSION: There were no
      significant differences among the sensitivities and specificities of the HTLV
      I/II ELISAs (p values, 0.056-0.438). The WB and PCR assays were much more
      specific than the other serologic assays (p</=0.03). However, the PCR assay is
      significantly (p<0.001) more sensitive than any of the serologic assays in the
      detection of HTLV-II infection. Thus, optimal detection of HTLV-II infection
      would seem to require both serologic and DNA PCR assays.

PMID- 10960519
TI  - Transfusion-related sepsis due to Serratia liquefaciens in the United States.
AB  - BACKGROUND: Severe, often fatal, transfusion reactions due to bacterial
      contamination of blood components continue to occur. Serratia liquefaciens, an
      unusual human pathogen, is a recently recognized potential cause of transfusion
      related sepsis. CASE REPORTS: Five episodes of transfusion-related sepsis and
      endotoxic shock due to S. liquefaciens were reported to the CDC from July 1992
      through January 1999. One episode has been described. The remaining four, all
      fatal, are described here: three associated with RBC transfusion and one
      associated with transfusion of platelets. In each instance, the source of
      contamination could not be found. The implicated units tended to be older (mean
      RBC age 28 days), and visual discoloration was noted in each RBC unit, although
      usually in retrospect. CONCLUSION: S. liquefaciens is an increasingly recognized
      cause of transfusion-related sepsis and is associated with a high mortality rate.
      S. liquefaciens can contaminate both RBCs and platelets, but the mechanism(s) of
      contamination remain unknown. Increased attention to pretransfusion visual
      inspection may avert the transfusion of some S. liquefaciens-contaminated RBC
      units. However, more sensitive rapid diagnostic tests are needed to further
      reduce the risk of transfusion-related sepsis and endotoxic shock.

PMID- 10960520
TI  - Differentiation of autologous ABO, RHD, RHCE, KEL, JK, and FY blood group
      genotypes by analysis of peripheral blood samples of patients who have recently
      received multiple transfusions.
AB  - BACKGROUND: After multiple transfusions, the serologic typing of autologous blood
      group phenotypes is difficult, because of mixed RBC populations. The genotyping
      of ABO, Rh, Kell, Kidd, and Duffy systems could be used to determine autologous
      blood group antigen status. STUDY DESIGN AND METHODS: Blood samples from patients
      and donors were analyzed before and after 26 multiple-transfusion events. An
      average of 6.9 non-WBC-reduced RBC units with an average age of 5.9 days were
      administered per transfusion event. The average period of blood sampling after
      transfusions was 5.3 days. All samples were serologically phenotyped for ABO, Rh,
      Kell, Kidd, and Duffy. Pretransfusion, posttransfusion, and buccal samples from
      patients were genotyped for the corresponding alleles by a uniform PCR sequence
      specific primer protocol that allowed their simultaneous determination within 3
      hours. RESULTS: All posttransfusion samples exhibited mixed-cell populations of
      various blood group systems on serologic testing. Genotyping from peripheral
      blood produced results identical to the autologous blood group phenotypes,
      regardless of the amount of blood transfused or of the length of the sampling
      period after transfusion. CONCLUSION: A fast and reliable PCR-sequence-specific
      primer DNA genotyping assay for simultaneous determination of autologous ABO, Rh,
      Kell, Kidd, and Duffy blood groups can be performed on peripheral blood samples,
      even though the patients have recently received multiple transfusions.

PMID- 10960521
TI  - Description of serologic features in autoimmune lymphoproliferative syndrome.
AB  - BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a recently
      recognized and rare disorder associated with inherited defects in the FAS: gene
      or other regulators of lymphocyte apoptosis. It is characterized by massive
      lymphadenopathy; splenomegaly; autoimmunity including episodes of immune
      hemolytic anemia, thrombocytopenia, and neutropenia.(1) The serologic basis for
      immune cytopenias associated with ALPS has not been previously characterized.
      STUDY DESIGN AND METHODS: RBC, granulocyte, and platelet serologies for ALPS
      patients and hepatitis C patients were assessed. Medical records were reviewed
      for clinical, immunologic, serologic, and transfusion history. Testing included:
      DAT; serum screening for antibodies to RBCs, granulocytes, platelets,
      cardiolipin, penicillin-coated RBCs, and human leukocyte antigens; antibody
      identification and IgG subclass; RBC phenotype. RESULTS: In a cohort of 11
      patients with apoptosis defects (eight with heterozygous FAS: gene mutations);
      many had histories of hemolytic anemia (7), thrombocytopenia (4), and/or
      leukopenia (11); nine received steroid therapy, seven underwent splenectomy; five
      had been remotely transfused. On the basis of serologic testing even when they
      were clinically stable, nine had positive DATs; two had alloantibodies; 6 had IgG
      and/or IgM antibodies to cardiolipin; seven had platelet-directed antibodies;
      three had granulocyte-directed antibodies; none had HLA antibodies. CONCLUSIONS:
      Nearly all ALPS patients have antibodies directed against one or more
      hematopoietic cell lineages. Serologic testing is critical in the evaluation of
      these individuals and when transfusion is indicated, red cells that are matched
      for clinically significant C, E, and K antigens should be considered.

PMID- 10960522
TI  - Differential expression of the duffy antigen receptor for chemokines according to
      RBC age and FY genotype.
AB  - BACKGROUND: The Duffy (Fy) blood group (also known as Duffy antigen receptor for
      chemokines, or DARC) may be involved in regulation of the level of circulating
      proinflammatory chemokines, and it is an obligatory receptor on RBCs for the
      human malaria parasite Plasmodium vivax. STUDY DESIGN AND METHODS: Because
      quantification of Fy expression by using RBCs of various ages will not detect
      acute changes associated with inflammatory states, and because P. vivax
      exclusively invades reticulocytes, a flow cytometric method was developed to
      measure the level of surface expression of Fy. Reticulocytes and mature RBCs from
      persons with different genotypes (GATA-1 T-->C promoter mutation at nt -46; FY*A
      and FY*B in the ORF) were used. RESULTS: Expression of the Fy6 epitope, which is
      required for P. vivax invasion, was 49 +/- 19 percent higher on reticulocytes
      than on mature RBCs, regardless of donor genotype (p<0.0001). Fy6 levels were
      approximately 50 percent lower in persons who were heterozygous for the GATA-1
      promoter mutation and were significantly lower on reticulocytes and mature RBCs
      of the FY*B/FY*B genotype than on those of the FY*A/FY*A or FY*A/FY*B genotype.
      CONCLUSION: Fy has greater expression on reticulocytes than on mature RBCs in
      flow cytometry. This method may be useful in further studies of this antigen,
      such as characterization of reticulocytes and RBC phenotypes across populations,
      in response to chemokine regulation, and in the context of susceptibility to P.
      vivax and other parasites.

PMID- 10960523
TI  - Infectious disease markers in young blood donors. Retrovirus Epidemiology Donor
      Study.
AB  - BACKGROUND: To evaluate whether the active recruitment of young donors of high
      school and college age could affect the safety of the blood supply, prevalence
      and incidence rates of infectious disease markers among donors aged 17 to 18 and
      19 to 22 were compared to those in donors 23 years of age and older. STUDY DESIGN
      AND METHODS: Over 15 percent of 4.97 million whole blood donations were collected
      from donors aged 17 to 18 and 19 to 22. Prevalence (per 100,000 first-time
      donors) and incidence (per 100,000 person-years) rates for confirmed infectious
      diseases were compared between age groups. RESULTS: The prevalence estimates for
      HIV, HCV, HTLV-I and -II, and serologic tests for syphilis (STS) were
      significantly lower among first-time donors aged 17 to 18 and 19 to 22 than among
      those 23 to 44 years of age. HBsAg prevalence was higher in the first-time donors
      in the younger groups than in first-time donors in the older group because of
      higher prevalences among Asians and blacks. The incidence rates of HIV, HCV, and
      HTLV were similar in the younger groups and the older group. Donors 19 to 22
      years of age had a higher incidence rate of estimated HBV than did donors aged 23
      to 44 and 45+ (p<0.001), but the incidence rate of STS was lower in donors aged
      17 to 18 and 19 to 22 than in donors 23 to 44 and 45+ years of age (p<0.001).
      CONCLUSION: Aggressive recruitment of school-age donors should not result in an
      increased risk of transmission-transmitted infections, with the possible
      exception of HBV.

PMID- 10960524
TI  - In vitro collection and posttransfusion engraftment characteristics of MNCs
      obtained by using a new separator for autologous PBPC transplantation.
AB  - BACKGROUND: A clinical study was performed to evaluate the peripheral blood
      progenitor cell (PBPC) collection, transfusion, and engraftment characteristics
      associated with use of a blood cell separator (Amicus, Baxter Healthcare). STUDY
      DESIGN AND METHODS: Oncology patients (n = 31) scheduled for an autologous PBPC
      transplant following myeloablative therapy were studied. PBPCs were mobilized by
      a variety of chemotherapeutic regimens and the use of G-CSF. As no prior studies
      evaluated whether PBPCs collected on the Amicus separator would be viable after
      transfusion, to ensure patient safety, PBPCs were first collected on another cell
      separator (CS-3000 Plus, Baxter) and stored as backup. The day after the CS-3000
      Plus collections were completed, PBPC collections intended for transfusion were
      performed using the Amicus instrument. For each transplant, >2.5 x 10(6) CD34+
      PBPCs per kg of body weight were transfused. RESULTS: Clinical data collected on
      the donors immediately before and after PBPC collection with the Amicus device
      were comparable to donor data similarly obtained for the CS-3000 Plus
      collections. While the number of CD34+ cells and the RBC volume in the collected
      products were equivalent for the two devices, the platelet content of the Amicus
      collections was significantly lower than that of the CS-3000 Plus collections
      (4.35 x 10(10) platelets/bag vs. 6.61 x 10(10) platelets/bag, p<0.05). Collection
      efficiencies for CD34+ cells were 64 +/- 23 percent for the Amicus device and 43
      +/- 14 percent for the CS-3000 Plus device (p<0.05). The mean time to engraftment
      for cells collected via the Amicus device was 8.7 +/- 0.7 days for >500 PMNs per
      microL and 9.7 +/- 1.5 days to attain a platelet count of >20,000 per microL
      equivalent to data in the literature. No CS-3000 Plus backup cells were
      transfused and no serious adverse events attributable to the Amicus device were
      encountered. CONCLUSIONS: The mean Amicus CD34+ cell collection efficiency was
      better (p<0.05) than that of the CS-3000 Plus collection. Short-term engraftment
      was durable. The PBPCs collected with the Amicus separator are safe and effective
      for use for autologous transplant patients requiring PBPC rescue from high-dose
      myeloablative chemotherapy.

PMID- 10960525
TI  - Inactivation of WBCs in RBC suspensions by photoactive phenothiazine dyes:
      comparison of dimethylmethylene blue and MB.
AB  - BACKGROUND: The transfusion of blood components containing WBCs can cause
      unwanted complications, which include virus transmission, transfusion-associated
      GVHD, alloimmunization, febrile reactions, and immunomodulation. Phototreatment
      with 4 microM of dimethylmethylene blue (DMMB) and 13 J per cm(2) of white light
      irradiation has previously been shown to be an effective way to inactivate
      different models of enveloped and nonenveloped viruses in RBC suspensions, with
      minimum damage to RBCs. The present study compares WBC photoinactivation in buffy
      coat after DMMB or MB phototreatment under virucidal conditions. STUDY DESIGN AND
      METHODS: Buffy coat diluted to 30-percent Hct was treated with the dye and white
      light. Isolated WBCs were assayed for cell proliferation and viability by an
      assay using a tetrazolium compound, limiting dilution analysis, DNA
      fragmentation, and flow cytometry assays. RESULTS: DMMB and 2.5 J per cm(2) of
      light phototreatment can inactivate T cells to the limit of detection by limiting
      dilution analysis (>4.76 log reduction). No WBC proliferation activity was
      observed after DMMB and 3.8 J per cm(2) of light. DNA degradation after DMMB
      phototreatment was light dependent. In addition, DMMB phototreatment induced
      apoptosis in WBCs. In contrast, MB phototreatment under virucidal conditions did
      not cause significant changes in the viability of WBCs. Neither DNA degradation
      nor signs of apoptosis were observed after MB phototreatment. CONCLUSION: DMMB
      phototreatment inactivates T-lymphocytes, the cells that cause GVHD.

PMID- 10960526
TI  - Thrombopoietin and the TPO receptorduring platelet storage.
AB  - BACKGROUND: For most cells, the addition of a specific growth factor has improved
      cellular viability by preventing programmed cell death (apoptosis). To determine
      whether the platelet-specific hematopoietic growth factor thrombopoietin (TPO)
      might improve platelet viability, endogenous TPO and the platelet TPO receptor
      were analyzed during storage, and the effect of recombinant TPO on platelet
      viability was assessed. STUDY DESIGN AND METHODS: During platelet storage, TPO
      stability was assessed by SDS-PAGE, TPO receptor function was measured, and the
      platelet TPO receptor was characterized by a (125)I-rHuTPO competitive-binding
      assay. A recombinant TPO, pegylated recombinant human megakaryocyte growth and
      development factor (PEG-rHuMGDF), was added to platelet concentrates during
      storage, and its effect on pH, LDH, and metabolic activity was determined.
      RESULTS: During storage, the molecular weight and concentration of endogenous TPO
      (125 +/- 19 pg/mL) and exogenous TPO (5720 +/- 140 pg/mL) were constant for 12
      days; the number (33 +/- 4), binding affinity (149 +/- 33 pM), and function of
      the platelet TPO receptors were constant for 7 days. Metabolic activity measured
      with the MTT and MTS assays closely correlated with changes in the pH and LDH.
      The addition of PEG-rHuMGDF did not alter the pH, LDH, or metabolic activity of
      platelets during storage, but it did increase by 65 percent the uptake of (35)S
      methionine into platelets. Finally, platelet concentrates obtained from donors
      treated with PEG-rHuMGDF retained normal metabolic activity for 12 days, as
      compared with 5 to 6 days for normal platelet concentrates. CONCLUSIONS: TPO and
      its platelet receptor are present in normal amounts and have normal function
      during platelet storage. The addition of recombinant TPO increased platelet
      methionine transport but did not alter platelet viability during storage. Other
      means to prevent apoptosis during platelet storage should be considered, and the
      measurement of platelet metabolic activity by MTT and MTS assays may assist this
      effort.

PMID- 10960527
TI  - Correlation of in vivo and in vitro functions of fresh and stored human
      platelets.
AB  - BACKGROUND: Long-term storage of human platelets has been hindered by the loss of
      function of the platelets stored under current protocols. Novel preservation
      methods have encouraged examination of platelet function of cells preserved by
      cooling and freezing. The function of the platelets was assessed by using both in
      vitro assays and an in vivo rabbit bleeding model. STUDY DESIGN AND METHODS:
      Human platelets were stored in the presence or absence of 2 microM: cytochalasin
      B and 80 microM: EGTA/AM at 4 degrees C for 14 days or by freezing in the
      presence or absence of 5 percent DMSO. After the storage period, the platelets
      were resuspended in normal saline and infused into rabbits. Platelet function was
      assessed in vivo in a kidney bleeding model and in vitro by platelet-induced clot
      retraction and by platelet aggregation. RESULTS: Platelets stored at either 4
      degrees C or -145 degrees C exhibited shorter survival times in the rabbit
      circulation than did fresh platelets. Platelets cooled to 4 degrees C, in both
      the presence or absence of cytochalasin B and EGTA/AM treatment, or frozen in the
      absence of DMSO were not effective in halting bleeding. However, frozen DMSO
      treated platelets were as effective as fresh platelets in stopping bleeding. In
      vitro assays showed that cooled platelets treated with cytochalasin B and egtazic
      acid/AM and frozen DMSO-treated platelets retained 30 to 40 percent platelet
      function, while the cooled and frozen control samples exhibited no platelet
      induced clot retraction. With thrombin as the agonist, only frozen DMSO-treated
      platelets exhibited a tendency to aggregate, although at only 22 percent of the
      aggregation function of fresh platelets. CONCLUSION: It is possible to freeze
      platelets and retain in vivo efficacy if the cryopreservative DMSO is included in
      the preparation. In vitro responses were greatly reduced by all of the storage
      protocols, but it may not be necessary to retain 100 percent in vitro function to
      have a platelet substitute or storage product that functions satisfactorily in
      vivo.

PMID- 10960528
TI  - A hypotonic storage solution did not prolong the viability of RBCs.
AB  - BACKGROUND: Hypotonic storage solutions and WBC filtration are both reported to
      improve RBC viability. This study tested the ability of an investigational
      hypotonic storage solution (AS-24, Medsep Corp.) to extend the viability of
      liquid-stored RBCs to 8 weeks. STUDY DESIGN AND METHODS: In a pair of crossover
      trials, 11 RBC units, WBC-reduced by filtration and stored in AS-24 for 8 weeks,
      were compared with units from the same donors that were stored for 6 weeks in AS
      3, and 13 RBC units, WBC-reduced by filtration and stored in AS-3 for 8 weeks,
      were compared with units from the same donors that were stored for 6 weeks in AS
      3. Viability was measured by the (51)Cr/(99m)Tc double-isotope method. RESULTS:
      RBC viability at 8 weeks averaged 64 +/- 3 percent in the AS-24 units and 67 +/-
      2 percent in the AS-3 units. It was equal at 77 +/- 3 percent and 77 +/- 2
      percent after 6 weeks' storage in AS-3 in both trials. CONCLUSIONS: Prestorage
      WBC reduction and storage in AS-24 did not extend RBC viability to 8 weeks. The
      improved viability previously demonstrated with storage of dilute suspensions of
      RBCs in hypotonic solutions is probably caused by factors other than the
      hypotonicity.

PMID- 10960529
TI  - The effects of phosphate, pH, and AS volume on RBCs stored in saline-adenine
      glucose-mannitol solutions.
AB  - BACKGROUND: RBC ATP concentrations are the most important correlate of RBC
      viability. Tests were performed to determine whether increased AS volume, pH, and
      phosphate content increased stored RBC ATP concentrations. STUDY DESIGN AND
      METHODS: In three studies, packed RBCs were pooled in groups of 3 or 4 units and
      realiquoted as combined units to reduce intradonor differences. Pooled units were
      stored in the licensed ASs, AS-1 or AS-5, which contain saline, adenine, glucose,
      and mannitol (SAGM), or in experimental ASs (EASs) containing SAGM and disodium
      phosphate. Ten pools were stored in AS-1 at RBC concentrations equivalent to 100,
      200, or 300 mL of AS. Six pools were stored in 100, 200, 300, or 400 mL volumes
      of EAS-61. Ten pools were stored in 100 mL of AS-5, 200 mL of EAS-61, or 300 mL
      of EAS-64. RBC ATP concentration and other measures of RBC metabolism and
      function were measured weekly. RESULTS: RBC ATP concentrations decreased sooner
      with storage in increasing volumes of AS-1. In EAS-61 and EAS-64, RBC ATP
      concentrations initially increased and stayed elevated longer with increasing AS
      volume. CONCLUSIONS: The addition of disodium phosphate to SAGM AS increases the
      RBC ATP concentrations. Reducing storage Hct appears to have a separate
      beneficial effect in reducing hemolysis.

PMID- 10960530
TI  - Successful storage of RBCs for 9 weeks in a new additive solution.
AB  - BACKGROUND: This study explored the effect of storing packed RBCs suspended in
      200 mL of an alkaline, hypotonic, experimental additive solution (EAS 61). STUDY
      DESIGN AND METHODS: Packed RBC units prepared from RBCs collected from healthy
      donors in CPD were stored for 8 (n = 10) and 9 (n = 10) weeks under blood bank
      conditions after the addition of 200 mL of EAS 61 (adenine, 2 mM:; dextrose, 110
      mM:; mannitol, 55 mM:; NaCl, 26 mM:; Na(2)HPO(4), 12 mM:). Standard methods were
      used for in vitro assays. The 24-hour in vivo autologous recoveries were measured
      with (51)Cr. RESULTS: Mean +/- SD recoveries at 8 and 9 weeks were 81 +/- 7 and
      77 +/- 7 percent. After 9 weeks, the ATP of the RBCs was 81 percent of the
      initial value, hemolysis was 0.35 percent, supernatant potassium was 46 mEq per
      L, and the morphologic index was 94.1. CONCLUSION: Packed RBCs suspended in 200
      mL of EAS 61 can be stored satisfactorily for 9 weeks. Longer RBC storage should
      reduce outdating, increase availability of transfusions in remote locations, and
      improve the efficiency of autologous donor programs.

PMID- 10960531
TI  - Successful storage of RBCs for 10 weeks in a new additive solution.
AB  - BACKGROUND: The effect of storing packed RBCs suspended in 300 mL of an alkaline,
      experimental additive solution (EAS 64) was explored. STUDY DESIGN AND METHODS:
      RBC units prepared from blood collected from healthy donors into CPD were WBC
      reduced and stored for 10 weeks under blood bank conditions after the addition of
      300 mL of EAS 64 (adenine, 2 mM:; dextrose, 50 mM:; mannitol, 20 mM:; NaCl, 75
      mM:; Na(2)HPO(4), 9 mM:). For comparison, non-WBC-reduced units from the same
      donors were stored in a different additive solution (AS-1, Baxter Healthcare) for
      6 weeks. Standard methods were used for the in vitro assays. The 24-hour in vivo
      recoveries were measured by using (51)Cr- and (99m)Tc-labeled RBCs. RESULTS: Mean
      recovery in the EAS 64 units after 10 weeks was 84 +/- 8 percent, the same as in
      the AS-1 units stored for 6 weeks. For EAS 64 and AS-1 units, respectively, the
      ATP of the RBCs was 85 percent and 64 percent of the initial value, hemolysis was
      0.43 percent and 0.63 percent, supernatant potassium was 24 mEq per L and 44 mEq
      per L, and the morphologic index was 98 and 71. CONCLUSION: RBCs suspended in 300
      mL of EAS 64 can be stored satisfactorily for 10 weeks. Longer RBC storage should
      reduce outdating, increase availability of transfusions in remote locations, and
      improve the efficiency of autologous donor programs.

PMID- 10960532
TI  - Public perception of the risk of blood transfusion.
AB  - BACKGROUND: Health policymakers are concerned about the proportion of people who
      say they are unwilling to receive a blood transfusion. This article examines how
      social, cultural, and political factors affect the perceived risk of
      transfusions. STUDY DESIGN AND METHODS: Data were collected as part of a large
      national telephone survey of 1204 people conducted in the United States in 1997
      and 1998. The survey elicited images associated with blood transfusions and
      contained questions about the perceived risk of the blood supply, sensitivity to
      stigma, world views, trust, and demographics. RESULTS: The results showed that a
      substantial proportion of people do not consider the US blood supply to be safe
      and say they would not accept blood if hospitalized. The images evoked most
      frequently by the stimulus phrase "blood transfusions" were related to AIDS or
      HIV. The people who tend to perceive the greatest personal and public risk from
      blood transfusions are female, nonwhite, and less educated, and they have not
      previously received a transfusion. Sensitivity to stigma, mistrust, one's
      perceived inability to control hazardous activities and technologies, and
      fatalistic and egalitarian world views tend to be associated with heightened
      concern about the risk of blood transfusions. CONCLUSION: Risk perceptions need
      to be monitored to anticipate and deal with problems of public acceptance. Risk
      management strategies should be tailored to the specific characteristics of
      individuals that are important determinants of the perceived risk of
      transfusions.

PMID- 10960533
TI  - The iron hypothesis:does iron play a role in atherosclerosis?

PMID- 10960534
TI  - Prevention of bacterial contamination of whole blood.

PMID- 10960535
TI  - The use of stent-grafts in thoracic aortic disease.

PMID- 10960536
TI  - Endovascular stents and stent-grafts: is heparin coating desirable?
AB  - Heparins are glycosaminoglycans that, in addition to their anticoagulant
      activity, have interactions with growth factors and other glycoproteins. These
      interactions may stimulate neointimal hyperplasia when heparin is delivered
      locally on stents and stent-grafts. Modifying the structure of heparin to retain
      anticoagulant activity while minimizing these stimulatory effects on the vascular
      endothelium is desirable and may be achieved by understanding the relationships
      between the structure and function of the various parts of the heparin molecule.

PMID- 10960537
TI  - Anesthesia practice and clinical trends in interventional radiology: a European
      survey.
AB  - PURPOSE: To determine current European practice in interventional radiology
      regarding nursing care, anesthesia, and clinical care trends. METHODS: A survey
      was sent to 977 European interventional radiologists to assess the use of
      sedoanalgesia, nursing care, monitoring equipment, pre- and postprocedural care,
      and clinical trends in interventional radiology. Patterns of sedoanalgesia were
      recorded for both vascular and visceral interventional procedures. Responders
      rated their preferred level of sedoanalgesia for each procedure as follows: (a)
      awake/alert, (b) drowsy/arousable, (c) asleep/arousable, (d) deep sedation, and
      (e) general anesthesia. Sedoanalgesic drugs and patient care trends were also
      recorded. A comparison was performed with data derived from a similar survey of
      interventional practice in the United States. RESULTS: Two hundred and forty
      three of 977 radiologists responded (25%). The total number of procedures
      analyzed was 210,194. The majority (56%) of diagnostic and therapeutic vascular
      procedures were performed at the awake/alert level of sedation, 32% were
      performed at the drowsy/arousable level, and 12% at deeper levels of sedation.
      The majority of visceral interventional procedures were performed at the
      drowsy/arousable level of sedation (41%), 29% were performed at deeper levels of
      sedation, and 30% at the awake/alert level. In general, more sedoanalgesia is
      used in the United States. Eighty-three percent of respondents reported the use
      of a full-time radiology nurse, 67% used routine blood pressure/pulse oximetry
      monitoring, and 46% reported the presence of a dedicated recovery area. Forty
      nine percent reported daily patient rounds, 30% had inpatient hospital beds, and
      51% had day case beds. CONCLUSION: This survey shows clear differences in the use
      of sedation for vascular and visceral interventional procedures. Many, often
      complex, procedures are performed at the awake/alert level of sedation in Europe,
      whereas deeper levels of sedation are used in the United States. Trends toward
      making interventional radiology a clinical specialty are evident, with 51% of
      respondents having day case beds, and 30% having inpatient beds.

PMID- 10960538
TI  - Failing hemodialysis arteriovenous fistula and percutaneous treatment: imaging
      with CT, MRI and digital subtraction angiography.
AB  - PURPOSE: To evaluate failing hemodialysis arteriovenous fistulas with helical CT
      angiography (CTA), MR angiography (MRA), and digital subtraction angiography
      (DSA), and to compare the efficacy of the three techniques in detecting the
      number, location, grade, and extent of stenoses and in assessing the technical
      results of percutaneous transluminal angioplasty (PTA) and stenting. METHODS:
      Thirteen patients with Brescia-Cimino arteriovenous fistula malfunction underwent
      MRA and CTA of the fistula and, within 1 week, DSA. A total of 11 PTAs were
      performed; in three cases an MR-compatible stent was placed. DSA served as the
      gold standard for comparison in all patients. The presence, site, and number of
      stenoses or occlusions and the technical results of percutaneous procedures were
      assessed with DSA, CTA, and MRA. RESULTS: MRA underestimated a single stenosis in
      one patient; CTA and MRA did not overestimate any stenosis. Significant artifacts
      related to stent geometry and/or underlying metal were seen in MRA sequences in
      two cases. CONCLUSIONS: CT and MRI can provide information regarding the degree
      of vascular impairment, helping to stratify patients into those who can have PTA
      (single or multiple stenoses) versus those who require an operative procedure
      (occlusion). Conventional angiography can be reserved for candidates for
      percutaneous intervention.

PMID- 10960539
TI  - Percutaneous CT-guided biopsy of the lung: comparison between aspiration and
      automated cutting needles using a coaxial technique.
AB  - PURPOSE: To compare the accuracy and complication rate of two different CT-guided
      transthoracic needle biopsy techniques: fine needle aspiration and an automated
      biopsy device. METHODS: Two consecutive series of respectively 125 (group A) and
      98 (group B) biopsies performed using 20-22 gauge coaxial fine needle aspiration
      (group A) and an automated 19.5 gauge coaxial biopsy device (group B) were
      compared in terms of their accuracy and complication rate. RESULTS: Groups A and
      B included respectively 100 (80%) and 77 (79%) malignant lesions and 25 (20%) and
      18 (21%) benign lesions. No significant difference was found between the two
      series concerning patients, lesions, and procedural variables. For a diagnosis of
      malignancy, a statistically significant difference in sensitivity was found
      (82.7% vs 97.4%) between results obtained with the automated biopsy device and
      fine needle aspiration respectively. For a diagnosis of malignancy, the false
      negative rate of the biopsy result was significantly higher (p <0.005) in group A
      (17%) than in group B (2.6%). For a specific diagnosis of benignity, no
      statistically significant difference was found between the two groups (44% vs
      26%) but the automated biopsy device provided fewer indeterminate cases. There
      was no difference between the two groups concerning the pneumothorax rate, which
      was 20% in group A and 15% in group B, or the hemoptysis rate, which was 2.4% in
      group A and 4% in group B. CONCLUSION: For a diagnosis of malignancy when a
      cytopathologist is not available on-site, automated biopsy devices provide a
      lower rate of false negative results and a similar complication rate to fine
      needle aspiration.

PMID- 10960540
TI  - Temporary vena cava filters and ultrahigh streptokinase thrombolysis therapy: a
      clinical study.
AB  - PURPOSE: To assess the efficacy of temporary vena cava filters in patients
      undergoing ultrahigh-dose streptokinase thrombolysis for iliocaval thrombosis and
      to determine therapy success and filter and therapy complications. METHODS: Forty
      five patients were studied regarding extension and characteristics of thrombosis,
      duration, success, and complications of thrombolysis therapy, filter type, access
      route, pulmonary embolisms, and filter complications. RESULTS: Complete
      recanalization was achieved in 57% of cases. Filters were inserted predominantly
      via a transbrachial route. One fatal pulmonary embolism (2%) occurred 1 day after
      starting thrombolysis. No other pulmonary embolism was noted. Other complications
      were induced by thrombolysis alone (n = 12), thrombolysis and filter (n = 9), and
      filter alone (n = 11). CONCLUSION: Fatal pulmonary embolisms as a complication of
      ultrahigh-dose treatment of pelvic or caval thrombosis can not safely be
      prevented by the temporary vena cava filters currently available. Filter design
      needs to be improved.

PMID- 10960542
TI  - Simulation model based on non-newtonian fluid mechanics applied to the evaluation
      of the embolic effect of emulsions of iodized oil and anticancer drug.
AB  - PURPOSE: To verify the difference in embolic effect between oil-in-water (O-W)
      and water-in-oil (W-O) emulsions composed of iodized oil and an anticancer drug,
      epirubicin, using a simulation model based on non-Newtonian fluid mechanics.
      METHODS: Flow curves of pure iodized oil and two types of O-W and W-O emulsions
      immediately and 1 hr after preparation were examined with a viscometer. Using the
      yield stress data obtained, we simulated the stagnation of each fluid with steady
      flow in a rigid tube. RESULTS: The W-O emulsions were observed to stagnate in the
      thin tube at a low pressure gradient. However, the embolic effect of the W-O
      emulsions decreased 1 hr after preparation. The O-W emulsions were stable and did
      not stagnate under the conditions in which the W-O emulsions stagnated.
      CONCLUSION: The simulation model showed that the embolic effect of the W-O
      emulsions was superior to that of the O-W emulsions.

PMID- 10960541
TI  - Percutaneous gastrostomy in patients who fail or are unsuitable for endoscopic
      gastrostomy.
AB  - PURPOSE: Percutaneous endoscopic gastrostomy (PEG) is not possible or fails in
      some patients. We aimed to categorize the reasons for PEG failure, to study the
      success of percutaneous radiologic gastrostomy (PRG) in these patients, and to
      highlight the associated technical difficulties and complications. METHODS: Forty
      two patients (28 men, 14 women; mean age 60 years, range 18-93 years) in whom PEG
      failed or was not possible, underwent PRG. PEG failure or unsuitability was due
      to upper gastrointestinal tract obstruction or other pathology precluding PEG in
      15 of the 42 patients, suboptimal transillumination in 22 of 42 patients, and
      advanced cardiorespiratory decompensation precluding endoscopy in five of 42
      patients. T-fastener gastropexy was used in all patients and 14-18 Fr catheters
      were inserted. RESULTS: PRG was successful in 41 of 42 patients (98%). CT
      guidance was required in four patients with altered upper gastrointestinal
      anatomy. PRG failed in one patient despite CT guidance. In the 16 patients with
      high subcostal stomachs who failed PEG because of inadequate transillumination,
      intercostal tube placement was required in three and cephalad angulation under
      the costal margin in six patients. Major complications included inadvertent
      placement of the tube in the peritoneal cavity. There was one case of hemorrhage
      at the gastrostomy site requiring transfusion and one case of superficial
      gastrostomy site infection requiring tube removal. Minor complications included
      superficial wound infection in six patients, successfully treated with routine
      wound toilette. CONCLUSION: We conclude that PRG is a safe, well-tolerated and
      successful method of gastrostomy and gastrojejunostomy insertion in the
      technically difficult group of patients who have undergone an unsuccessful PEG.
      In many such cases optimal clinical evaluation will suggest primary referral for
      PRG as the preferred option.

PMID- 10960543
TI  - Are covered stents really effective at closing esophagotracheal fistulas? Results
      of an animal study.
AB  - PURPOSE: To determine whether covered self-expanding metal stents successfully
      exclude experimentally created esophagotracheal fistulas. METHODS:
      Esophagotracheal fistulas were surgically created in the upper third of the
      esophagus in 12 minipigs and immediately sealed by implantation of a covered self
      expanding metal stent (20 mm expanded diameter) in the esophagus. Before the
      animals were killed, after 3, 7, 14, 28, 30, and 36 days, the position of the
      stent and the sealing of the fistula were monitored fluoroscopically. The
      esophagus, trachea, and both lungs were examined histologically. RESULTS:
      Creation of an esophagotracheal fistula was successful in all cases. All fistulas
      were widely patent at autopsy. The technical success rate for stent deployment
      and initial sealing of the fistula was 100%. During follow-up, five stents
      migrated distally, but none into the stomach. Therefore, the fistula was no
      longer excluded in five animals. In seven animals the stent sealed the fistula
      until the death of the animal. Tracheal narrowing necessitated additional
      tracheal stenting in three animals. Two minipigs died due to aspiration of food.
      Histologic examination showed signs of aspiration in all animals with stents in
      place for longer than 2 weeks. CONCLUSION: This experimental animal study
      revealed worse results for sealing of esophagotracheal fistulas with covered self
      expanding metal stents than have been reported for the clinical use of these
      devices.

PMID- 10960544
TI  - Cardiac perforation and tamponade during transjugular intrahepatic portosystemic
      shunt placement.
AB  - A patient developed acute severe hemodynamic compromise during a transjugular
      intrahepatic portosystemic shunt (TIPS) procedure for intractable ascites. Rapid
      clinical and radiographic evaluation of the patient disclosed pericardial blood
      and cardiac tamponade as the cause, probably due to right heart perforation from
      guidewire and catheter manipulation. The tamponade was successfully treated
      percutaneously, and the patient survived. Cardiac tamponade should be considered
      in the differential diagnosis of patients who develop hypotension during TIPS
      placement.

PMID- 10960545
TI  - Treatment of stomal variceal hemorrhage with TIPS: case report and review of the
      literature.
AB  - We report a case in which recurrent hemorrhage from stomal varices was
      successfully treated by placement of a TIPS in a patient with prior colectomy for
      inflammatory bowel disease. Although several treatment options have been reported
      for this entity we believe that TIPS offers minimally invasive and definitive
      treatment.

PMID- 10960547
TI  - Iatrogenic arteriovenous fistula in a renal allograft: the result of a TAD
      guidewire injury.
AB  - A case is presented of an iatrogenic arteriovenous fistula developing in a renal
      allograft following guidewire manipulation during transplant renal artery
      angioplasty. Hyperdynamic flow through the fistula was causing a shunt of blood
      away from the renal cortex as demonstrated on sonography and scintigraphy.
      Selective embolization was performed, correcting the maldistribution of flow to
      the peripheral renal cortex. The diagnosis and difficulty in management of
      asymptomatic renal arteriovenous fistulae is also discussed.

PMID- 10960546
TI  - Ischemic cholangitis caused by transcatheter hepatic arterial chemoembolization
      10 months after resection of the extrahepatic bile duct.
AB  - We report a case of ischemic cholangitis that occurred after transcatheter
      hepatic arterial chemoembolization (TAE). Ten months prior to TAE the patient had
      undergone central bisegmentectomy for hepatocellular carcinoma with resection of
      the extrahepatic bile duct. Eleven days after TAE, he developed suppurative
      cholangitis and multiple organ failure. Prior surgical ligation of the
      peribiliary arteries around the extrahepatic bile duct followed by TAE was
      considered to have played a crucial role in the development of ischemic
      cholangitis. This case demonstrates the importance of blood flow from the
      peribiliary arteries for the survival of the biliary epithelium.

PMID- 10960548
TI  - Stent recanalization of chronic portal vein occlusion in a child.
AB  - An 8-year-old boy with a 21/2 year history of portal hypertension and repeated
      bleedings from esophageal varices, was referred for treatment. The 3.5-cm-long
      occlusion of the portal vein was passed and the channel created was stabilized
      with a balloon-expandable stent; a portosystemic stent-shunt was also created.
      The portosystemic shunt closed spontaneously within 1 month, while the
      recanalized segment of the portal vein remained open. The pressure gradient
      between the intrahepatic and extrahepatic portal vein branches dropped from 17
      mmHg to 0 mmHg. The pressure in the portal vein dropped from 30 mmHg to 17 mmHg
      and the bleedings stopped. The next dilation of the stent was performed 12 months
      later due to an increased pressure gradient; the gastroesophageal varices
      disappeared completely. Further dilation of the stent was planned after 2, 4, and
      6 years.

PMID- 10960549
TI  - A novel method of macropathologic and arteriographic examination of carotid
      specimens obtained from autopsy.
AB  - Twenty carotid bifurcations were examined. During autopsy, carotid bifurcations
      were removed in toto. Unfixed carotids were ligated and cannulated for injection
      of an angiographic contrast medium followed by injection of a tissue-embedding
      medium at physiologic pressure and temperature. The carotid bifurcation was
      frozen and cut manually in 3-mm cross-sections. Photographs were then taken of
      every slice. Angiography, filling with tissue-embedding material, and sectioning
      were successful in all cases. In the macropathologic sections, the extent,
      configuration and location of atherosclerotic lesions could be identified.

PMID- 10960550
TI  - Palliation of pyloric stenosis caused by gastric cancer using an endoscopically
      placed covered ultraflex stent: covered stent inside an occluded uncovered stent.
AB  - A 71-year-old man developed pyloric stenosis caused by gastric cancer. Vomiting
      and nausea resolved after the insertion of an uncovered Ultraflex stent (length
      10 cm, inner diameter 18-23 mm) through a 7-cm-long stenosis, and the patient was
      able to eat a soft diet. After 6 weeks, stent occlusion occurred due to tumor
      ingrowth and accumulation of food residue. Endoscopic observation showed a very
      narrow residual lumen. A covered Ultraflex stent (length 10 cm, inner diameter 18
      23 mm) was inserted through the first stent and expanded to its maximum diameter
      over the next 2 days. The patient's vomiting and nausea improved rapidly. He died
      6 months after the second stenting procedure, from metastatic tumor spread,
      having remained free of nausea and vomiting. In this case, a covered metallic
      stent prevented tumor ingrowth and maintained gastrointestinal patency.

PMID- 10960551
TI  - Spontaneous arteriovenous fistulas of the lower extremities: angiographic
      demonstration in five patients with peripheral vascular disease.

PMID- 10960553
TI  - Announcements

PMID- 10960552
TI  - Re: Renal artery stenosis associated with peripheral emboli and infarcts:
      treatment with thrombolysis and angioplasty.

PMID- 10960555
TI  - Reference values and prediction equations for FVC and FEV(1) in the Greek
      elderly.
AB  - Spirometry prediction equations obtained from middle-age adults, when
      extrapolated for the elderly, may lead to inaccurate interpretations. The purpose
      of this study was to determine prediction equations for forced vital capacity
      (FVC) and forced expiratory volume (FEV(1)) in the Greek elderly population.
      Spirometry prediction equations for normal FVC and FEV(1) have been derived from
      tests on 71 healthy persons (38 men, 33 women) aged older than 60 years (range,
      65-85 years), nonsmokers, white race, urban population using techniques and
      equipment that meet American Thoracic Society recommendations. Regression
      analysis using age, height, and weight as independent variables was used to
      provide prediction equations and values for both sexes. The FVC age coefficient
      in this healthy group was about 47.19 mL/y for elderly men and 34.27 mL/y for
      elderly women, and the FEV(1) age coefficient was about 52.8 mL/y for elderly men
      and 46.4 mL/y for elderly women. Values from this study predicted equations were
      compared with those from some of the most commonly used sources of spirometry
      predicted equations. The FVC and FEV(1) predicted values were found to be of less
      mean square error than that of other compared studies. Higher correlation is
      between FVC and FEV(1) predicted values by the present model and FVC and FEV(1)
      observed values in both sexes. The higher correlation between FVC and FEV(1)
      predicted and observed from this study allows the use of our model for predicting
      in a rather reliable way the FVC and FEV(1) for elderly Greek individuals.

PMID- 10960554
TI  - HDL and vitamin E in plasma and the expression of SR-BI on lung cells during rat
      perinatal development.
AB  - Vitamin E is the most important lipophilic antioxidant, and beneficial effects on
      oxidant-caused injuries have been reported. Neonates are at high risk of
      oxidative injury in the lung and other organs because of a low vitamin E
      concentration, but the optimal timing of the application, a safe application
      form, and the optimal dosage of vitamin E are not known at present. We recently
      showed that alveolar type II cells take up vitamin E preferentially from high
      density lipoprotein (HDL), probably by means of the candidate HDL receptor,
      scavenger receptor class B type I (SR-BI; Kolleck et al. Free Rad Biol Med 27;
      882-890, 1999). Therefore, both the HDL-bound vitamin E in plasma and the
      expression of SR-BI on alveolar type II cells may determine the supply of the
      cells with vitamin E. We show here that the plasma level of vitamin E, total and
      HDL cholesterol, and the ratio of vitamin E to polyunsaturated fatty acids and to
      total fatty acids decrease during fetal rat development, reaching the minimum at
      the postconceptual day 21 (day -1). These parameters increase thereafter to about
      the same levels as in adult rats. SR-BI is not detectable until day -1 on fetal
      lung cells, but the expression during the postnatal phase follows the same
      pattern as the plasma lipid constituents. We conclude that the ability of
      alveolar type II cells to take up vitamin E develops perinatally in mature
      neonates. This aspect also has to be considered when the optimal timing of
      supplementation for the protection of preterm neonates with vitamin E against
      oxidative lung injury is established.

PMID- 10960556
TI  - Mediators and oxygen radicals in hyperpnea-induced airway constriction of guinea
      pigs.
AB  - Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been suggested to
      be important modulating factors for the hyperpnea-induced bronchoconstriction
      (HIB) of guinea pigs. In this study, we tested the hypothesis that LTs and oxygen
      radicals modulate HIB by triggering TK release. Eighty-five Hartley guinea pigs
      were divided into four groups: control, dimethylthiourea (DMTU), FPL 55712, and
      A63162. DMTU is the scavenger for hydroxyl radical. FPL 55712 is an antagonist of
      LT receptor, whereas A63162 is an inhibitor of lipoxygenase. Each group was
      further divided into three subgroups: baseline, hyperpnea, and recovery. Each
      animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We
      measured dynamic respiratory compliance (Crs), maximal expiratory flow at 50%
      total lung capacity (V(max(50))), and forced expiratory volume in 0.1 s
      (FEV(0.1)) during the baseline and recovery periods. Hyperpnea caused significant
      decreases in Crs, V(max(50)), and FEV(0. 1), indicating HIB in the control group.
      Pretreatment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P
      (SP) levels increased progressively during the experiment in all groups. However,
      both FPL 55712 and A63162, but not DMTU, significantly decreased SP levels.
      Similarly, lung malondialdehyde (MDA) contents increased progressively during the
      experiment in the control group. Neither FPL 55712 nor A63162 significantly
      affected the increase. On the contrary, DMTU significantly attenuated the
      increase in MDA during the recovery period. These results suggest that inhibition
      of LTs leads to suppression at SP levels and HIB, whereas DMTU attenuates HIB by
      means of other mechanisms.

PMID- 10960557
TI  - Ebselen decreases ozone-induced pulmonary inflammation in rats.
AB  - We studied the effects of ebselen on rat lung inflammatory responses against
      ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a
      single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg)
      significantly decreased pulmonary inflammation as indicated by the albumin
      concentration and the number of neutrophils in the bronchoalveolar lavage fluid
      18 h after the ozone exposure. Although treatment with ebselen did not alter the
      macrophage expression of inducible nitric oxide synthase after the ozone
      exposure, it did markedly inhibit the nitration reaction of tyrosine residues,
      suggesting that ebselen scavenges peroxynitrite during ozone-induced pulmonary
      inflammation. Treatment with ebselen also enhanced the pulmonary expression of
      both copper, zinc, and manganous superoxide dismutases at the same time point.
      These enzymes may also contribute to a decrease in the formation of peroxynitrite
      by lowering the concentration of superoxide. Thus, ebselen represents a useful
      compound for protecting against certain acute lung injuries by modulating the
      oxidant-related inflammatory process.

PMID- 10960558
TI  - Lipopolysaccharide tolerance in relation to intrabronchial influx of neutrophils
      in the rat.
AB  - Lipopolysaccharide (LPS) is a potent chemotactic component for polymorphonuclear
      leukocytes (PMN, neutrophils). Since LPS tolerance was first described, many
      studies have been reported about the hyporesponsiveness in vitro corresponding to
      attenuating production of proinflammatory cytokines. We hypothesized that in vivo
      daily exposure to LPS stimuli impairs neutrophil accumulation in the rat airway.
      Interleukin 8 (IL-8) and/or CXC-chemokine, a neutrophil chemoattractant and
      activating cytokine, have been implicated as proinflammatory mediators in gram
      negative respiratory tract infections. It is possible that the tolerance to LPS
      has occurred in relation to this chemoattractant cytokine production. To settle
      this issue, we examined whether the neutrophil count in bronchoalveolar lavage
      fluid (BALF) decreases after daily inhalation of Pseudomonas aeruginosa LPS into
      the rat airway. Repeated inhalation of LPS into the airway resulted in reduction
      in neutrophil recruitment. We measured rat CXC-chemokine (rat GRO/CINC1) levels
      in recovered BALF. There were noted reductions of rat GRO corresponding to the
      diminished neutrophil trafficking. We also confirmed that the HLA-DR positive
      lymphocyte number in BALF gradually increased after daily inhalation of LPS.
      These results suggest that continuous stimuli of LPS mitigate the accumulation of
      inflammatory cells in the airway by reducing chemokine production with a
      consequent change in the appearance of local inflammation to a chronic state.

PMID- 10960559
TI  - Angiotensin-converting enzyme activity by canine pulmonary microvascular and
      central pulmonary artery endothelial cells exposed to hypoxia.
AB  - To compare the amount of angiotensin-converting enzyme (ACE) activity in
      pulmonary artery endothelial cells from different sites and to examine the effect
      of severe hypoxia (less than 1% of O(2) in 5% CO(2) and 95% N(2)) on the ACE
      activity expressed by these cells, endothelial cells were harvested and cultured
      from canine main pulmonary artery by scraping the luminal surface of the artery
      and from canine pulmonary artery microvessels by infusing chilled buffer with
      microcarrier beads and 0.02% ethylenediamine tetraacetic acid (EDTA). ACE
      activity in cell lysates and culture medium was evaluated by fluorometric assay
      with hippuryl-L-histidyl-L-leucine as a substrate. ACE activity in cell lysates
      and postculture medium of pulmonary microvascular endothelial cells (PMVEC) was
      higher than in cell lysates and culture medium of central pulmonary artery
      endothelial cells (PAEC). However, hypoxia suppressed cellular ACE activity in
      both PAEC and PMVEC. The degree of suppression of ACE activity by hypoxia, which
      was determined as (ACE activity in normoxia - ACE activity in hypoxia)/ACE
      activity in normoxia x 100(%), was larger in PMVEC than in PAEC. The pulmonary
      microvasculature may be a greater source of ACE than central pulmonary artery,
      and the ACE activity of pulmonary microvascular endothelial cells seem to be
      sensitive to hypoxia, although the small diameter of the vessels improves
      conditions for interaction of blood-borne substance with endothelial enzymes.

PMID- 10960593
TI  - Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres
      derived from embryonic rat spinal cord.
AB  - Recent advances in the isolation and characterization of neural precursor cells
      suggest that they have properties that would make them useful transplants for the
      treatment of central nervous system disorders. We demonstrate here that spinal
      cord cells isolated from embryonic day 14 Sprague-Dawley and Fischer 344 rats
      possess characteristics of precursor cells. They proliferate as undifferentiated
      neurospheres in the presence of EGF and bFGF and can be maintained in vitro or
      frozen, expanded and induced to differentiate into both neurons and glia.
      Exposure of these cells to serum in the absence of EGF and bFGF promotes
      differentiation into astrocytes; treatment with retinoic acid promotes
      differentiation into neurons. Spinal cord cells labeled with a nuclear dye or a
      recombinant adenovirus vector carrying the lacZ gene survive grafting into the
      injured spinal cord of immunosuppressed Sprague-Dawley rats and non
      immunosuppressed Fischer 344 rats for up to 4 months following transplantation.
      In the presence of exogenously supplied BDNF, the grafted cells differentiate
      into both neurons and glia. These spinal cord cell grafts are permissive for
      growth by several populations of host axons, especially when combined with
      exogenous BDNF administration, as demonstrated by penetration into the graft of
      axons immunopositive for 5-HT and CGRP. Thus, precursor cells isolated from the
      embryonic spinal cord of rats, expanded in culture and genetically modified, are
      a promising type of transplant for repair of the injured spinal cord.

PMID- 10960594
TI  - Glutamate neurotransmission and nitric oxide interaction within the ventrolateral
      medulla during cardiovascular responses to muscle contraction.
AB  - We previously reported that nitric oxide, within the RVLM and CVLM, plays an
      opposing role in modulating cardiovascular responses during static muscle
      contraction [B.J. Freda, R.S. Gaitonde, R. Lillaney, A. Ally, Cardiovascular
      responses to muscle contraction following microdialysis of nitric oxide precursor
      into ventrolateral medulla, Brain Res. 828 (1999) 60-67]. In this study, we
      determined whether the effects of administering L-arginine, a precursor for the
      synthesis of nitric oxide, and N(G)-monomethyl-L-arginine (L-NMMA), a nitric
      oxide synthase inhibitor, into the rostral (RVLM) and caudal (CVLM) ventrolateral
      medulla on cardiovascular responses elicited during static muscle contraction
      were mediated via an alteration of localized glutamate concentrations using
      microdialysis techniques. In experiments within the RVLM (n=8), muscle
      contraction increased MAP and HR by 21+/-2 mmHg and 22+/-3 bpm, respectively.
      Glutamate increased from 1.1+/-0.4 to 4.4+/- 0.6 ng/5 microl measured from
      bilateral RVLM areas. Microdialysis of L-arginine (1.0 microM) for 30 min
      attenuated the contraction-evoked increases in MAP, HR, and glutamate levels.
      After subsequent microdialysis of L-NMMA (1.0 microM) into the RVLM, contraction
      augmented the pressor and tachycardic responses and glutamate release. In
      experiments within CVLM (n=8), muscle contraction increased MAP and HR by 22+/-3
      mmHg and 20+/-2 bpm, respectively. Glutamate increased from 0.8+/-0. 4 to 3.6+/
      0.6 ng/5 microl measured from the CVLM. L-Arginine augmented the cardiovascular
      responses and glutamate release and L-NMMA attenuated all the effects. Results
      suggest that nitric oxide within the RVLM and CVLM plays opposing roles in
      modulating cardiovascular responses during static exercise via decreasing and
      increasing, respectively, extracellular glutamate levels.

PMID- 10960596
TI  - Fluoro-Jade B: a high affinity fluorescent marker for the localization of
      neuronal degeneration.
AB  - Fluoro-Jade B, like its predecessor Fluoro-Jade, is an anionic fluorescein
      derivative useful for the histological staining of neurons undergoing
      degeneration. However, Fluoro-Jade B has an even greater specific affinity for
      degenerating neurons. This notion is supported by the conspicuous staining of
      degenerating neuronal elements with minimal background staining. This improved
      signal-to-noise ratio means that fine neuronal processes including distal
      dendrites, axons and axon terminals can be more readily detected and documented.
      Although the staining time and dye concentration are reduced, the method is as
      rapid, simple and reliable as the original Fluoro-Jade technique. Like Fluoro
      Jade, Fluoro-Jade B is compatible with a number of other labeling procedures
      including immunofluorescent and fluorescent Nissl techniques.

PMID- 10960595
TI  - Presynaptic effect of 7-OH-DPAT on evoked [3H]-acetylcholine release in rat
      striatal synaptosomes.
AB  - The objective of the present experiments was to study the presynaptic effect of 7
      hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT, a D(2)-like dopamine
      receptor agonist) on [3H]-acetylcholine ([3H]-ACh) release induced by potassium
      (15 mM, 25 mM and 60 mM), potassium channel-blockers (4-aminopyridine, 4-AP;
      tetraethylammonium, TEA and quinine) and veratridine to gain insight into the
      mechanisms involved in the activation of the D(2) dopamine-receptor subtype
      located at striatal cholinergic nerve terminals. 7-OH-DPAT (1 microM) inhibited
      the evoked [3H]-ACh release induced by K(+) 15 mM in a similar percentage than
      that obtained during basal conditions (30% and 27%, respectively). Nevertheless,
      in the presence of 25 mM and 60 mM of K(+) the inhibitory effect of 7-OH-DPAT was
      completely abolished. 4-AP (1-100 microM) and TEA (1 and 5 mM) significantly
      enhanced [3H]-ACh release, showing 69.32%+/-7.60% (P<0.001) and 52.27%+/-5.64%
      (P<0.001), respectively, at the highest concentrations tested. In these
      conditions, 7-OH-DPAT (1 microM) inhibited the release induced by potassium
      channel-blockers approximately 25-27%. Quinine (0.1-1 microM) did not alter [3H]
      ACh release either in the presence or absence of 7-OH-DPAT. Veratridine 10 microM
      evoked [3H]-ACh release in the presence of a low-calcium medium, but in such
      conditions 7-OH-DPAT (1 microM) did not modify the neurotransmitter release in
      the absence or presence of veratridine. Present data indicate that activation of
      the presynaptic D(2) dopamine receptor inhibits the [3H]-ACh release by
      increasing K(+) conductance, as high K(+) concentrations abolished the inhibitory
      control of 7-OH-DPAT on [3H]-ACh release. This effect could be mediated by
      potassium channels different from those sensitive to 4-AP, TEA and quinine. In
      addition, the presynaptic D(2) dopamine-receptor activation seems to not involve
      changes in intracellular Ca(2+).

PMID- 10960597
TI  - Deciphering the origin of Met-enkephalin and Leu-enkephalin in Lobe-finned fish:
      cloning of australian lungfish proenkephalin.
AB  - The previous detection of Met-enkephalin and Leu-enkephalin in the CNS of the
      Australian lungfish, Neoceratodus forsteri, in a molar ratio comparable to
      mammals suggested that the lungfish proenkephalin precursor should contain the
      sequences of both Met-enkephalin and Leu-enkephalin as seen for mammalian
      proenkephalin. However, the cloning of a full-length proenkephalin cDNA from the
      CNS of the Australian lungfish indicates that the organization of this precursor
      is more similar to amphibian proenkephalin than mammalian proenkephalin. The
      Australian lungfish cDNA is 1284 nucleotides in length and the open reading frame
      (267 amino acids) contains seven opioid sequences (GenBank #AF232671). There are
      five copies of the Met-enkephalin sequence flanked by sets of paired basic amino
      acid proteolytic cleavage sites and two C-terminally extended forms of Met
      enkephalin: YGGFMRSL and YGGFMGY. As seen for amphibians, no Leu-enkephalin
      sequence was detected in the Australian lungfish proenkephalin cDNA. The fact
      that Leu-enkephalin has been identified by radioimmunoassay and HPLC analysis in
      the CNS of the Australian lungfish indicates that a Leu-enkephalin-coding gene,
      distinct from proenkephalin, must be expressed in lungfish. Potential candidates
      may include a prodynorphin- or other opioid-like gene. Furthermore, the absence
      of a Leu-enkephalin sequence in lungfish and amphibian proenkephalin would
      suggest that the mutations that yielded this opioid sequence in tetrapod
      proenkephalin occurred at some point in the radiation of the amniote vertebrates.

PMID- 10960598
TI  - Neurotoxic APP C-terminal and beta-amyloid domains colocalize in the nuclei of
      substantia nigra pars reticulata neurons undergoing delayed degeneration.
AB  - Increased amyloid precursor protein (APP) expression and intracellular
      accumulation of its toxic fragments have been associated with acute neuronal
      death processes. However, the role of APP fragments in delayed neurodegeneration
      remains poorly understood. We have characterized the appearance of APP domains in
      rat substantia nigra pars reticulata (SNpR) neurons targeted for delayed
      degeneration following neurotoxic striatal lesion. From 4 to 8 days postlesion
      (dpl) SNpR neurons ipsilateral to the lesion showed marked cytosolic accumulation
      of full length APP. Moreover, the nuclei of affected neurons also showed intense
      immunoreactivity (IR) for APP C-terminal and beta-amyloid domains but not for an
      N-terminal sequence. These data suggested the presence of APP C-terminal
      fragment. The absence of nuclear IR for a beta1-40 specific antibody supports
      this conclusion. Ultrastructural analysis of nigral sections from 6 dpl rats
      using a beta-amyloid domain antibody showed pronounced accumulation of immunogold
      silver reaction product in the nuclei of affected SNpR neurons that was absent in
      control, contralateral SNpR neurons. These findings suggest that intranuclear APP
      C-terminal fragment may play a role in genomic events contributing to delayed
      neuron degeneration in the SNpR.

PMID- 10960599
TI  - Suprachiasmatic nucleus projections to the paraventricular thalamic nucleus in
      nocturnal rats (Rattus norvegicus) and diurnal nile grass rats (Arviacanthis
      niloticus).
AB  - The circadian pacemaker of the suprachiasmatic nucleus (SCN) is likely to control
      the timing of the sleep-wake cycle in mammals by modulating the daily activity
      patterns of brain regions important in sleep and wakefulness. One such brain
      region is the paraventricular nucleus of the thalamus (PVT). In both nocturnal
      rats and the diurnal rodent Arvicanthis niltoicus (Nile grass rat), expression of
      Fos (the product of the immediate-early gene c-fos) in the PVT increases at times
      of day when the animals are most active. To compare the projections of the SCN to
      the PVT in these two species, the retrograde tracer cholera toxin (beta subunit;
      CTbeta) was microinjected into the PVT and the SCN was examined to identify
      labeled neurons. Further, the PVT-projecting SCN cells containing either arginine
      vasopressin (AVP) or gastrin releasing peptide (GRP) were also compared between
      species. In both nocturnal rats and diurnal Nile grass rats, the SCN sends a
      substantial projection to the PVT. In both species, many PVT-projecting SCN
      neurons contain AVP, and few contain GRP. Other work has shown that some AVP
      containing neurons of the SCN function differently in rats and Nile grass rats.
      Projections from functionally distinct SCN neurons to the PVT may contribute to
      the difference in the temporal distribution of sleep and wakefulness seen between
      these two species.

PMID- 10960600
TI  - Glucose-regulated dopamine release from substantia nigra neurons.
AB  - Glucose modulates substantia nigra (SN) dopamine (DA) neuronal activity and GABA
      axon terminal transmitter release by actions on an ATP-sensitive potassium
      channel (K(ATP)). Here, the effect of altering SN glucose levels on striatal DA
      release was assessed by placing microdialysis probes into both the SN and
      striatum of male Sprague-Dawley rats. Reverse dialysis of 20 mM glucose through
      the SN probes transiently decreased striatal DA efflux by 32% with a return to
      baseline after 45 min despite constant glucose levels. During 50 mM glucose
      infusion, striatal DA efflux increased transiently by 50% and returned to
      baseline after 60 min. Infusion of 100 mM glucose produced a transient 25%
      decrease in striatal DA efflux followed by a sustained 50% increase above
      baseline. Efflux increased by a further 30% when the GABA(A) antagonist
      bicuculline (50 microM) was added to the 100 mM glucose infusate. At basal
      glucose levels, nigral bicuculline alone raised striatal DA efflux by 31%
      suggesting a tonic GABA inhibitory input to the DA neurons. The sulfonylurea
      glipizide (50 microM) produced a transient 25% increase in striatal DA release
      that became sustained when bicuculline was added. Thus, striatal DA release is
      affected by changing SN glucose levels. This response may well reflect the known
      effect of glucose on K(ATP) channel activity on both SN DA neurons and GABA axon
      terminals in the substantia nigra. These interactions could provide a mechanism
      whereby glucose modulates motor activity involved in food intake.

PMID- 10960602
TI  - Cholinergic differentiation triggered by blocking cell proliferation and
      treatment with all-trans-retinoic acid.
AB  - This study determined whether the effect of all-trans-retinoic acid (t-RA) on
      markers of cholinergic differentiation in a murine septal cell line, SN56.B5.G4,
      differed depending upon the cell's proliferative status. To develop a model of
      non-proliferating cells, aphidicolin, a DNA alpha-polymerase inhibitor, was used.
      Cessation of proliferation by aphidicolin increased intracellular choline and
      acetylcholine (ACh) levels in the absence of change to choline acetyltransferase
      (ChAT) activity and mRNA and vesicular ACh transporter (VAChT) mRNA. Importantly,
      the response to t-RA differed depending upon proliferative status. Consistent
      with previous reports, t-RA increased ChAT and VAChT mRNA, ChAT activity and
      intracellular ACh levels in proliferating SN56 cells with no effect on
      intracellular choline levels. When cells were treated with t-RA while undergoing
      proliferative arrest, an additive effect of combined treatment was observed on
      ACh levels; nevertheless, this was only accompanied by an increase in choline
      levels, VAChT and ChAT mRNAs, but not ChAT activity. Indeed, aphidicolin
      treatment completely suppressed the t-RA-induced increase in ChAT activity
      observed in proliferating cells. To explore the response to t-RA in post-mitotic
      cells, a sequential treatment of aphidicolin and t-RA was employed. t-RA
      treatment was ineffective in increasing ACh and choline levels, over and above
      that observed with the aphidicolin treatment alone. Comparable to the combined
      treatment, sequential treatment lead to an increase in ChAT mRNA without any
      increase in ChAT activity. In conclusion, both the magnitude and the mechanism(s)
      of action whereby t-RA enhances the cholinergic phenotype of SN56 cells is
      dependent upon the cell's proliferative status.

PMID- 10960601
TI  - Differential cellular regulation of the mitochondrial permeability transition in
      an in vitro model of 1,3-dinitrobenzene-induced encephalopathy.
AB  - Exposure to 1,3-dinitrobenzene (DNB) is associated with neuropathologic changes
      in specific brainstem nuclei, mediated by oxidative stress and mitochondrial
      dysfunction. The expression of Bcl-2-family proteins as a function of sensitivity
      to 1, 3-dinitrobenzene (DNB)-induced mitochondrial permeability transition (MPT)
      was examined in C6 glioma and SY5Y neuroblastoma cells. Neuroblastoma cells were
      10-fold more sensitive than glioma cells to DNB-induced decreases in
      mitochondrial reducing potential, measured by reduction of the tetrazolium
      compound, 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT).
      The IC(50) values for DNB-related inhibition of MTT reduction were 107+/-25
      microM in SY5Y cells and 1047+/-101 microM in C6 cells. Levels of reactive oxygen
      species (ROS) were increased in both SY5Y and C6 cells following DNB exposure by
      4.6- and 6.0-fold above control, respectively. DNB caused abrupt depolarization
      of mitochondria in both neuroblastoma and glioma cells that was inhibited by
      trifluoperazine. The first order rate constants for mitochondrial depolarization
      were: C6, k=0.31+/-0.02 min(-1); SY5Y, k=0.14+/-0.01 min(-1). Onset of MPT
      occurred at 10-fold lower concentration of DNB in SY5Y cells than in C6 cells.
      The antioxidants, deferoxamine and alpha-tocopherol, effectively prevented DNB
      induced MPT in C6 and SY5Y cells, suggesting involvement of ROS in the initiation
      of MPT. Exposure to DNB resulted in decreased cellular ATP content in SY5Y cells
      and efflux of mitochondrial calcium in both SY5Y and C6 cells, concurrent with
      onset of MPT. The expression of Bcl-2, Bcl-X(L), and Bax was evaluated in both
      cell types by Western blot analysis. C6 glioma cells strongly expressed Bcl-X(L)
      and only weakly expressed Bcl-2 and Bax, whereas SY5Y neuroblastoma cells
      expressed lower levels of Bcl-X(L) and higher levels of both Bcl-2 and Bax.
      Collectively, these results suggest that higher constitutive expression of Bcl
      X(L), rather than Bcl-2, correlates with resistance to DNB-induced MPT in SY5Y
      and C6 cells and that differential regulation of the permeability transition pore
      may underlie the cell-specific neurotoxicity of DNB.

PMID- 10960603
TI  - A biphasic regulation of receptor mRNA expressions for growth hormone,
      glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute
      stress.
AB  - Acute stress increases circulating ACTH and glucocorticoid levels. The
      hippocampus (HIP) is a target of such stress hormones as glucocorticoid and it
      also expresses receptors for growth hormone (GH), particularly in the dentate
      gyms (DG). In order to understand the interactions between glucocorticoids and
      functions of GH in HIP during acute stress, the mRNA levels for GH receptor
      (GHR), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were
      investigated in DG in rats exposed to restraint stress in the water (RSW). Using
      in situ hybridization histochemistry (ISHH), high level expressions of GHR mRNA
      were detected in DG. These were down-regulated by 14% after 0.5 h of RSW and then
      up-regulated by 38% over the initial level after 4 h of RSW. This biphasic
      enhancement of GHR mRNA expression in DG followed the elevation of plasma
      glucocorticoid levels and paralleled with biphasic expressions of mRNAs for GR
      and MR in DG. Although circulating GH levels did not show any correlation with
      the hippocampal GHR mRNA expression, adrenalectomy (ADX) decreased GHR mRNA
      expression in DG, and the dexamethasone treatment (DEX; 20 microg/100 microl,
      i.p.) of ADX rats rapidly increased the GHR mRNA expression in DG. These results
      have suggested that the GHR mRNA expression in the DG is regulated, at least in
      part, by glucocorticoids and that GH may be involved in responses of the DG to
      acute stress.

PMID- 10960604
TI  - The action of pituitary adenylate cyclase activating polypeptide (PACAP) on
      passive avoidance learning. The role of transmitters.
AB  - In the present study, the action of PACAP 38 on one-way passive avoidance
      learning was investigated. PACAP-38 was administered into the lateral brain
      ventricle and the latency of the passive avoidance response was measured 24 h
      later. In order to study the possible roles of various neurotransmitters in
      mediating the action of PACAP on the consolidation of passive avoidance learning,
      the animals were pre-treated with receptor blockers in doses that per se proved
      to be ineffective. PACAP facilitated the learning, the consolidation of learning
      and the retrieval of the passive avoidance response. The following receptor
      blockers attenuated the action of PACAP on this consolidation: haloperidol,
      phenoxybenzamine, propranolol and methysergide. An antagonist of PACAP 38, PACAP
      6-38, and also nitro-L-arginine (the latter blocks the enzyme nitric oxide
      synthase) thereby inhibiting the formation of NO from L-arginine, completely
      blocked the action of PACAP 38 on consolidation. The following receptor blockers
      were ineffective: naloxone, bicuculline and atropine. The presented data suggest
      that PACAP 38 is able to improve the learning and memory processes in a passive
      avoidance paradigm. In this action, the PACAP 38 receptor and NO are important
      mediators. Dopaminergic, alpha- and beta-adrenergic mediation and serotonin
      receptors modified the action of PACAP 38, but they are probably not of great
      importance.

PMID- 10960605
TI  - Neuroprotective effects of a novel NMDA antagonist, Gacyclidine, after
      experimental contusive spinal cord injury in adult rats.
AB  - The aim of this study was to analyze the optimal time-window for neuroprotection
      by a novel NMDA antagonist, Gacyclidine, after experimental spinal cord injury,
      in terms of its functional, histopathological and electrophysiological effects.
      This molecule has already demonstrated its capacity for reducing the extent of an
      ischemic lesion and is currently experimented in a clinical trial of spinal cord
      injury. In this study, the spinal cord of rats was damaged by a contusive method
      and the animals were treated by saline or 1 mg/kg of Gacyclidine i.v., 10, 30, 60
      and 120 min after injury. The time-course of the motor score was evaluated on
      days 1, 7 and 18 after injury, and somatosensory evoked potentials were
      determined on day 20. The animals were then killed and the cross-sectional area
      of the spinal cord (at the epicenter of the injury, above and below the injury),
      was measured. Walking recovery was better (P<0.0125) in the group treated 10 min
      after injury than in the untreated injured animals after 18 days of injury. Motor
      performances were related to the preservation of a larger undamaged area of
      spinal cord at the level of the injury (P<0.0125). Somatosensory evoked potential
      amplitudes were also higher in this group. These results confirm that Gacyclidine
      attenuates spinal cord damage after an experimental spinal cord lesion. Recovery
      was better within the group treated 10 min after injury compared with the other
      groups, which certainly confirms that the acute time-course of glutamate release
      requires rapid pharmacological intervention to achieve good results.

PMID- 10960606
TI  - Selective neuronal vulnerability during experimental scrapie infection: insights
      from an ultrastructural investigation.
AB  - The goal was to test whether all neurons are equally susceptible to degeneration
      in response to PrP(Sc) scrapie infection. We tested this by immunogold GABA
      labeling. Our ultrastructural results indicates that GABAergic neurons are less
      vulnerable than other neuronal populations. This conclusion is supported by our
      findings: (1) reversal of the normal ratio of non-GABAergic to GABAergic neurons
      in the terminal stages, which implies that non-GABAergic neurons degenerated
      earlier, and (2) that the degeneration of GABAergic neurons occurs late in the
      disease after reactive astrogliosis, a response to nerve cell death.

PMID- 10960607
TI  - Valproate modulates the expression of methylphenidate (ritalin) sensitization.
AB  - Repeated administration of amphetamine, cocaine, and methylphenidate (MPD) has
      been reported to elicit behavioral sensitization to their locomotor and
      stereotypic effects in rodents. GABAergic drugs have been shown to inhibit
      behavioral effects of stimulants. The objective of the present study was to
      determine whether single or multiple administration of sodium valproate, a GABA
      agonist, would prevent the expression of sensitization to the locomotor effect of
      MPD once it has developed. Twenty-eight male Sprague-Dawley rats were randomized
      into three treatment groups: a control group received only 2.5 mg/kg MPD during
      the 14-day cycle, a group received a single 50 mg/kg valproate injection on Day
      9, and a group received multiple 50 mg/kg valproate injection on Days 9-13. Rats
      were housed in test cages and behavioral activities were recorded for 14
      consecutive days. All injections were given between 12:00 h and 14:00 h. Multiple
      injection of MPD elicited sensitization to its locomotor and stereotypic effects.
      Single administration of valproate did not block the expression of sensitization
      in the four locomotor indices measured. However, multiple administration of
      valproate prevented MPD sensitization to horizontal activity, total distance and
      number of stereotypic movements.

PMID- 10960608
TI  - Par-4 induces cholinergic hypoactivity by suppressing ChAT protein synthesis and
      inhibiting NGF-inducibility of ChAT activity.
AB  - Profound reductions in choline acetyl-transferase (ChAT) activity are reliable
      markers for cholinergic hypoactivity associated with cognitive function deficit
      in Alzheimer's disease (AD). Par-4 (prostate apoptosis response-4) is a novel
      mediator of neuronal apoptosis associated with the pathogenesis of AD. Par-4
      contains a leucine zipper domain (Leu.zip) that presumably mediates protein
      protein interactions critical for its functions in apoptosis. Par-4 activity can
      be effectively blocked by overexpression of Leu. zip because it exerts a dominant
      negative action possibly by competitively blocking the interaction of Par-4 with
      other proteins. Whether Par-4 participates in regulation of cholinergic signaling
      has not been determined. We report that overexpression of Par-4 results in
      apoptotic and non-apoptotic reductions in ChAT activity in transfected PC12 cells
      following exposure to a toxic concentration (50 microM) of aggregated amyloid
      beta peptide 1-42 (Abeta 1-42) and a non-toxic concentration (1 microM) of
      soluble Abeta 1-42, respectively. Non-apoptotic reduction in ChAT activity
      induced by Par-4 can be completely blocked by co-overexpression of Leu.zip,
      indicating that enhanced Par-4 activity is a necessary event for cholinergic
      hypoactivity in PC12 cells. Further studies found that Par-4 induces non
      apoptotic reduction in ChAT activity by: (1) reducing ChAT protein levels
      following exposure to non-toxic concentration of Abeta, and (2) blocking the
      cellular capability to increase ChAT activity following exposure to nerve growth
      factor (NGF). The role of Par-4 in inducing cholinergic hypoactivity may have
      significant implications in the understanding and the treatment of memory
      impairment in AD.

PMID- 10960609
TI  - The role of the supplementary motor area in externally timed movement: the
      influence of predictability of movement timing.
AB  - A significant role in the planning and preparation for voluntary movement has
      been ascribed to secondary motor areas located on the medial wall of the cerebral
      hemispheres, and in particular to the supplementary motor area (SMA). Within the
      SMA, rostral and caudal subdivisions have been described, and differential roles
      have been attributed to these regions in relation to movement planning,
      preparation and execution. We have used functional magnetic resonance imaging
      (fMRI) to investigate the role of the SMA in the timing of movement execution, by
      recording the fMRI signal from mesial pre-motor areas and primary sensorimotor
      cortex (SM1) during the execution of a simple motor task externally cued at
      predictable (regular) and unpredictable (irregular) time intervals. The mean rate
      of movement was matched in both experiments. There was a greater activation of
      caudal than rostral SMA with both predictably and unpredictably cued movements,
      and a doubling of the signal when the timing of the motor response was
      unpredictable. In contrast, there was no difference in the activation of primary
      sensorimotor cortex with the two tasks. The data demonstrate that the caudal SMA
      has an important role in the execution of externally cued movements. The results
      also suggest a greater role for this region in the performance of unpredictably
      timed compared with predictably timed movements, however a model is proposed
      (based on electrophysiological data) which shows how the difference in functional
      signal in these two situations can be explained on the basis of a difference in
      the time course of neuronal activation in the SMA, rather than in the overall
      degree of activation.

PMID- 10960610
TI  - Editorial

PMID- 10960611
TI  - Update on cancer control in women.
AB  - The global cancer burden in women appears to have stabilized according to the
      most recent estimates available although the distribution of cancer types appears
      to be changing with a sharp contrast between the increase in the absolute numbers
      of breast cancers and a decline in cervix cancers. Prospects for cancer control
      in women appear to be good within our current knowledge and deserve close
      attention. Rates of lung cancer in women are increasing substantially in many
      countries and seem set to overtake breast cancer as the commonest form of cancer
      death in women in many parts of the world. These changes are due to the effects
      of cigarette smoking, a habit which women widely embraced during the second half
      of the last century. The high levels of smoking currently in young women, which
      have yet to have their full impact on death rates, constitute an important hazard
      not only for future cancer risks but for several other important causes of death.
      There is strong and consistent evidence that increased consumption levels of
      fruit and vegetables is associated with reduced risks of many common forms of
      cancer including breast cancer. Although the breast is the commonest form of
      cancer in women in most western countries, the etiology of this disease remains
      elusive and preventable causes remain to be identified. Endogenous hormones also
      appear to have a role in cancer risk in women: oral contraceptives seem to
      increase slightly the risk of breast cancer in users in the use and in the
      immediate post-use period, but 10 years after cessation the risk again returns to
      that of never users. Oral contraceptive usage also appears to be protective
      against ovarian and endometrial cancer. The use of hormonal replacement therapy
      (HRT) appears to increase the risk of endometrial cancer and a positive
      association with breast cancer risk appears to exist. Within our current
      knowledge of the epidemiology of cancer in women, the most important preventive
      strategies would appear to be the prevention of cigarette smoking and increased
      dietary intake of vegetables and fruits. Screening has also shown to be effective
      in reducing incidence and mortality of cervix cancer and mortality from breast
      cancer. Although more work is needed, it is becoming clear that there could be an
      important role of HPV testing to further enhance cervix cancer screening. There
      are important variations in survival from a variety of cancers which are due to
      factors unrelated to the tumor behavior and that there are significant variations
      in survival from cancer. Reduction of these gaps could lead to a reduction in
      cancer mortality and contribute towards increased prospects for cancer control in
      women.

PMID- 10960612
TI  - Chemical warfare among scleractinians: bioactive natural products from Tubastraea
      faulkneri Wells kill larvae of potential competitors.
AB  - Competition for space among scleractinians by overgrowth, overtopping,
      extracoelenteric digestion and the use of sweeper tentacles is well recognized,
      but another potential mode of competitive interaction, allelopathy, is largely
      uninvestigated. In this study, chemical extracts from Tubastraea faulkneri Wells
      were tested for deleterious effects on competent larvae of 11 other species of
      coral belonging to seven genera of four scleractinian families. Larvae exposed to
      extract concentrations from 10 to 500 ug ml(-1) consistently suffered higher
      mortality than larvae in solvent controls. Larvae of Platygyra daedalea (Ellis
      and Solander) and Oxypora lacera (Verrill) were the most sensitive, experiencing
      high mortality even at the lowest extract concentration. The toxic compounds from
      T. faulkneri did not kill any conspecific larvae. The estimated concentrations of
      active compounds within T. faulkneri tissues were 100-5000 times higher than the
      experimental concentrations. Pure compounds isolated from bioactive fractions of
      the extract were indole alkaloids identified as aplysinopsin, 6
      bromoaplysinopsin, 6-bromo-2'-de-N-methylaplysinopsin and its dimer. The first
      three occur in other non-zooxanthellate corals in the same family as T.
      faulkneri, whereas the dimer is novel. These compounds could act as
      allelochemicals that prevent potential competitors from recruiting in the
      vicinity of T. faulkneri colonies and help to pre-empt interactions with
      competitively dominant species.

PMID- 10960613
TI  - Breakdown of phytoplankton pigments in Baltic sediments: effects of anoxia and
      loss of deposit-feeding macrofauna.
AB  - We examined the decay of chlorophyll a and the carotenoid fucoxanthin in oxic and
      anoxic sediment microcosms, with and without the deposit-feeding benthic amphipod
      Monoporeia affinis, over 57 days at 5 degrees C. Deep frozen phytoplankton from
      the Baltic Sea proper was added to all but a few microcosms. The range of
      chlorophyll a and fucoxanthin decay rate constants observed in microcosms with
      phytoplankton addition was 0.04-0.07 day(-1). The fastest pigment decay and build
      up of chlorophyll breakdown products after phytoplankton addition were found in
      oxic treatments with amphipods. No effects of amphipods on pigment breakdown were
      found in anoxic treatments, or in treatments without phytoplankton addition.
      Greater losses of chlorophyll a in oxic (96%) than in anoxic (80%) treatments
      after 57 days indicates that preservation of sedimentary organic matter will be
      enhanced during periods of anoxia. Due to slow recruitment and recolonization in
      Baltic sediments, a single anoxic event may cause long-term (years) absence of
      significant macrobenthos. Anoxic events will thus not only reduce decay of plant
      pigments, and presumably other organic matter, while they last, but will also
      have longer-term effects, through elimination of macrofauna, which when present
      enhance organic matter decomposition.

PMID- 10960614
TI  - Relations between variable rates of growth, metabolic costs and growth
      efficiencies in individual Sydney rock oysters (Saccostrea commercialis).
AB  - Rock oysters from a mass selection trial were compared with wild-caught (control)
      oysters of the same age to determine the physiological basis for faster growth
      rates amongst the selected individuals, and to describe the associated
      flexibility in phenotypic traits of feeding, metabolism and growth. In
      confirmation of earlier studies, fast growth was associated with faster rates of
      feeding, reduced metabolic rates and lower metabolic costs of growth. Selected
      individuals deposited more protein, at a lower metabolic cost, than the controls.
      Control oysters, however, deposited more lipid than the selected oysters, though
      the unit costs of lipid deposition did not differ between categories. The results
      indicated a wide plasticity of physiological rates and efficiencies and
      demonstrated how, by selection, interactions between physiological traits can
      serve to enhance growth. If differences in lipid deposition observed here were
      indicative of different rates of gametogenesis, then the results also suggest
      that selection alters the balance between growth and reproduction. Whether these
      differences can be termed compensatory with respect to the life history of the
      species remains to be determined, but the results indicate some of the ways in
      which physiological flexibility may be expressed to effect different patterns of
      energy allocation.

PMID- 10960615
TI  - Effect of reproduction on escape responses and muscle metabolic capacities in the
      scallop Chlamys islandica Muller 1776.
AB  - In scallops, gametogenesis leads to mobilization of glycogen and proteins from
      the adductor muscle towards the gonad. This mobilization is likely to diminish
      the metabolic capacities of the adductor muscle and thereby the scallops' escape
      response. We examined the escape response in terms of number of valve claps until
      exhaustion, rate of clapping and the recovery during and after valve closure in
      adult scallops, Chlamys islandica, sampled at different stages in the
      reproductive cycle (immature, mature, before and after spawning). In parallel, we
      measured muscle glycogen, protein and phosphoarginine contents, the oxidative
      capacity of mitochondria isolated from the adductor muscle and levels of muscle
      enzymes which are active during exercise and recovery. The number of claps (24
      26), rate of clapping ( approximately 13 clapsmin(-1)) and phosphoarginine and
      arginine kinase levels were similar during the different reproductive stages. All
      immature scallops responded to restimulation immediately after opening their
      valves, while only 62% of mature, 82% of prespawned and 38% of spawned scallops
      responded. Immature animals completely recovered their initial swimming capacity
      within 4 h of opening their valves, but mature, prespawned and spawned scallops
      needed 18, 12 and 18 h, respectively. Overall phasic adductor muscle from mature,
      prespawned and spawned animals showed decreased glycogen phosphorylase,
      phosphofructokinase, pyruvate kinase (except for prespawned), octopine
      dehydrogenase and citrate synthase levels, a deterioration of the oxidative
      capacity of mitochondria and a marked decrease in glycogen content compared to
      immature scallops. Therefore, during gonadal maturation and spawning, C.
      islandica did not change its clapping capacity, but slowed its recuperation from
      exhausting burst exercise, both during and after valve closure, likely due to the
      decreased metabolic capacity of the adductor muscle.

PMID- 10960616
TI  - Ammonium and phosphate excretion in three common echinoderms from Philippine
      coral reefs.
AB  - The ammonium and phosphate excretion and oxygen consumption of three species of
      echinoderms (Tripneustes gratilla, Protoreaster nodosus and Ophiorachna
      incrassata) commonly encountered in Philippine coral reefs were investigated in
      relation to time of day (i.e. daytime between 10:00 and 12:00 h vs. nighttime
      between 22:00 and 24:00 h) and their recent feeding history (i.e. recently
      collected vs. short-term starvation for 3+/-1 days). The experiment used whole
      organism incubations and followed a nested hierarchical design. Ammonium
      excretion rates were 1447+/-310 nmolg(-1) DWh(-1) (mean+/-S.E., n=24) for T.
      gratilla, 361+/-33 for O. incrassata and 492+/-38 for P. nodosus. Ammonium
      excretion differed significantly among species, time of incubation and recent
      feeding history. Interaction between species and recent feeding history was also
      significant. The organisms excreted more ammonium during daytime except for
      starved specimens of O. incrassata. In addition, animals that were starved in the
      laboratory for a few days had a tendency to excrete more ammonium than recently
      collected specimens. Phosphate excretion rates were 25+/-13 nmolg(-1) DWh(-1) for
      T. gratilla, 10+/-2 for O. incrassata and 4+/-1 for P. nodosus. There were no
      significant differences in phosphate excretion among the three species of
      echinoderms, their recent feeding history and time of day. Oxygen consumption
      rates were 286+/-24 ug O(2)g(-1) DWh(-1) for T. gratilla, 64+/-3 for O.
      incrassata and 54+/-3 for P. nodosus. Oxygen consumption differed significantly
      among species and recent feeding history but differed only slightly with time of
      incubation. There was a significant correlation between oxygen consumption and
      ammonium excretion (r=0.48, P=0.018), and between oxygen consumption and
      phosphate excretion (r=0.41, P=0.047) for T. gratilla. The nutrient excretion by
      tropical echinoderms is another pathway by which inorganic nutrients are
      regenerated in coral reef communities. However, the quantity of nutrients
      excreted is dependent on the species of echinoderms, their nutritional status and
      time of day.

PMID- 10960617
TI  - A new method to estimate respiration rate of biological material based on the
      reduction of tetrazolium violet.
AB  - The traditional method for measuring the activity of the electron-transport
      system (ETS) gives an estimate of the potential respiration rate, since it
      measures the rate under saturated substrate conditions (V(max)). Accumulated
      literature data indicate that this does not relate closely to the actual
      respiration rate. The new method described here is based on reduction of
      tetrazolium violet in a homogenate with a natural level of substrates. The
      analytical protocol ensures that the spectrophotometric reading after 1 h
      incubation at 40 degrees C reflects the ambient amount of substrates available.
      This method is superior to the traditional ETS assay in giving a closer
      correlation with ambient respiration rate. A number of methodological tests have
      been performed and recommendations are given to optimize the measurements.
      Macrozooplankton species from the coastal waters of Sweden, representing
      different taxonomic and trophic groups, showed a range in respiration/ETS ratio
      from 1.1 to 2.9, and both inter- and intra-specific variability in this ratio
      were reduced by 50-70% compared with the traditional ETS assay. Results from
      other environments and for particulate organic matter indicate a similar general
      improvement. The new analytical assay is simple, cheap and well suited for
      fieldwork.

PMID- 10960618
TI  - Ontogeny of osmoregulation and salinity tolerance in a mangrove crab, Sesarma
      curacaoense (Decapoda: Grapsidae).
AB  - The grapsid crab Sesarma curacaoense is believed to represent the closest
      saltwater relative to the ancestor which gave rise to an adaptive radiation of
      endemic freshwater and terrestrial species on the island of Jamaica. Living in
      mangrove swamps with variable salinity conditions and showing semiterrestrial
      behaviour, S. curacaoense exhibits ecological adaptations to non-marine
      conditions. In laboratory experiments, we studied the salinity tolerance during
      development from hatching to the end of the first juvenile stage. Successful
      development through metamorphosis occurred in the full salinity range tested (15
      32 per thousand), although mortality was significantly enhanced and development
      delayed at 15 per thousand. In another series of experiments, we studied the
      ontogeny of the capability for osmoregulation, which is considered as the
      physiological basis of osmotic stress tolerance. Our results show that S.
      curacaoense is from hatching a fairly strong hyperosmoregulator in dilute media.
      This capability increased gradually from hatching throughout the larval and
      juvenile development. In seawater (32 per thousand) and at an enhanced salt
      concentration (44 per thousand), the zoeal stages remained hyperosmoconformers.
      The capability for hypoosmoregulation in concentrated media appeared first in the
      megalopa stage and increased thereafter. Adult crabs were observed to be strong
      hyper-hypo-osmoregulators in a salinity range from at least 1 per thousand to 44
      per thousand. The unusually early appearance of strong regulatory capabilities,
      particularly in dilute media, is interpreted as a physiological preadaptation
      that should have facilitated the evolutionary process of adaptive radiation in
      non-marine environments on Jamaica.

PMID- 10960619
TI  - Effects of symmetric and asymmetric fetal growth on pregnancy outcomes.
AB  - OBJECTIVE: To assess the prevalence of head circumference to abdomen
      circumference (HC/AC) asymmetry among small for gestational age (SGA) fetuses,
      and to determine the likelihood of adverse outcomes among asymmetric and
      symmetric SGA infants compared with their appropriate for gestational age (AGA)
      counterparts. METHODS: In a retrospective cohort study, we analyzed consecutive
      live-born singletons of women who had antepartum sonography within 4 weeks of
      delivery and delivered between January 1, 1989 and September 30, 1996. A
      gestational age-specific HC/AC nomogram was derived from our sonographic database
      of 33,740 nonanomalous live-born singletons. Asymmetric HC/AC was defined as
      greater than or equal to the 95th percentile for gestational age. RESULTS: Among
      1364 SGA infants, 20% had asymmetric HC/AC and 80% were symmetric. Asymmetric SGA
      infants were more likely to have major anomalies than symmetric SGA infants or
      AGA infants (14% versus 4% versus 3%, respectively; P <.001). After exclusion of
      anomalous infants, pregnancy-induced hypertension at or before 32 weeks'
      gestation and cesarean delivery for nonreassuring fetal heart rate were more
      common in the asymmetric SGA than the AGA group (7% versus 1% and 15% versus 3%,
      respectively; both P <.001). A neonatal outcome composite, including one or more
      of respiratory distress, intraventricular hemorrhage, sepsis, or neonatal death,
      was more frequent among asymmetric SGA than AGA infants (14% versus 5%, P =.001).
      Symmetric SGA infants were not at increased risk of morbidity compared with AGA
      infants. CONCLUSION: The minority of SGA fetuses with HC/AC asymmetry are at
      increased risk for intrapartum and neonatal complications.

PMID- 10960620
TI  - Transvaginal sonographic detection of embryonic-fetal abnormalities in early
      pregnancy.
AB  - OBJECTIVE: To estimate the detection rate of abnormalities by transvaginal
      ultrasound in early pregnancy. METHODS: We prospectively analyzed records of 3592
      sequential pregnant women at 10-16 weeks' (singleton) gestation (mean 13 weeks
      and 2 days). After exclusion of 114 women, there were 3478 women in the study.
      Each woman underwent a transvaginal sonographic survey for fetal anomalies as
      well as biometric measurements. Fetuses diagnosed with malformations were
      followed to delivery, and those without underwent transabdominal sonography at 18
      24 weeks' gestation. RESULTS: The anomaly detection rate by transvaginal
      ultrasound was 51.6% (33 of 64; 95% confidence interval [CI] 38.7, 64.2) in early
      pregnancy, and the detection rate by transvaginal ultrasound combined with second
      trimester transabdominal ultrasound was 84.4% (54 of 64; 95% CI 73.1, 92.2).
      Cystic hygroma and fetal hydrops were the anomalies detected most frequently by
      transvaginal ultrasound. Low detection rates for abnormalities of the face and of
      the cardiac, skeletal, and urinary systems were found even when both methods were
      used. CONCLUSION: Transvaginal sonography appears to be an effective way to
      identify many congenital fetal anomalies in early pregnancy. There is a good
      probability of diagnosing cystic hygroma and fetal hydrops, although other
      abnormalities, particularly heart defects, are associated with lower detection
      rates.

PMID- 10960621
TI  - Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes.
AB  - OBJECTIVE: To determine the perinatal effects of histologic chorioamnionitis on
      preterm neonates and the effectiveness of antenatal steroids in the presence of
      histologic chorioamnionitis. METHODS: We studied neonates at our institution who
      weighed 1750 g or less at birth from January 1990 through December 1997. The
      population was stratified primarily by presence of histologic chorioamnionitis
      and secondarily by exposure to antenatal steroids. Subgroups were compared by
      various perinatal outcomes and confounding variables. Student t test, chi(2),
      Fisher exact test, and logistic regression were used for analysis. RESULTS: Among
      1260 neonates entered, the placentas of 527 had evidence of histologic
      chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a
      lower mean gestational age, lower birth weight, and higher rate of major neonatal
      morbidities than those without it. After adjusting for confounding variables,
      histologic chorioamnionitis independently associated with lower gestational age,
      lower birth weight, and neonatal death. Among neonates exposed to antenatal
      steroids who had histologic chorioamnionitis, there was a significantly lower
      incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory
      distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular
      hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001),
      major brain lesions (7.7% compared with 18.4%, P <.001), patent ductus arteriosus
      (14.8% compared with 23.7%, P =.018), and neonatal death (8.3% compared with
      16.2%, P =.02), with no increase in rate of proven neonatal sepsis (18.3%
      compared with 14%, P =.24). CONCLUSION: Histologic chorioamnionitis increases
      major perinatal morbidity through its association with preterm birth and is
      independently associated with neonatal death. In the presence of histologic
      chorioamnionitis, antenatal steroids significantly decreased the incidence of
      RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain
      lesions, and neonatal mortality, without increasing neonatal sepsis.

PMID- 10960622
TI  - Human papillomavirus in the cervix and placenta.
AB  - OBJECTIVE: To determine the prevalence and association of human papillomavirus
      (HPV) infection in the cervices and placentas of pregnant women. METHODS:
      Cervical samples were taken from 179 of 226 women who had placental biopsies
      because of abnormal ultrasound findings or were older than 35 years, to detect
      HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was
      done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We
      found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test
      positive for HPV in their cervices. Logistic regression analyses showed decreased
      prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6
      PCR from the villus tissue was negative in the 147 cases examined. However, a
      significant contingency coefficient between low-risk HPV infection and elevated
      risk of chromosome aberration was found (&phi; = V = 0.15, P =.050). CONCLUSION:
      The infection rate of 24.6% in women without clinical symptoms of HPV infection
      was high, but there seemed to be no virus transmission to the placenta in women
      with subclinical infections. Low-risk cervical HPV infection might be associated
      with a slightly higher risk of abnormal fetal karyotype.

PMID- 10960623
TI  - Differences in umbilical venous and arterial leptin levels by mode of delivery.
AB  - OBJECTIVE: To investigate the differences in umbilical venous and arterial leptin
      levels by mode of delivery. METHODS: Subjects were 30 mothers who had elective
      cesarean deliveries and 34 mothers who had vaginal deliveries. Umbilical venous
      and arterial leptin levels were measured immediately after delivery. Maternal
      age, neonatal gender, neonatal birth weight, placental weight, and gestational
      duration were recorded. Inter- and intragroup comparisons were made in umbilical
      venous and arterial leptin levels and obstetric variables. Significant
      determinants of differences in umbilical venous and arterial leptin levels were
      investigated. RESULTS: Umbilical venous and arterial leptin levels were higher in
      the vaginal delivery group (n = 34) than in the cesarean group (n = 30) (P <.01).
      In the vaginal delivery group, umbilical venous leptin levels were significantly
      higher than arterial leptin levels (P <.001). These differences were still
      significant after adjustment for neonatal gender, neonatal birth weight, and
      placental weight. However, in the cesarean group, leptin levels did not differ
      between umbilical vein and artery. CONCLUSION: Placental leptin release is
      augumented during advanced labor.

PMID- 10960624
TI  - Change in cervical length after cerclage as a predictor of preterm delivery.
AB  - OBJECTIVE: To determine whether the degree of cervical lengthening after cerclage
      and whether serial follow-up measurements of cervical length after cerclage are
      predictive of pregnancy outcome. METHODS: Eighty women whose primary physician
      determined that a prophylactic (n = 50) or urgent cerclage (n = 30) was indicated
      had transvaginal ultrasonographic evaluation before and after cerclage.
      Thereafter, most women had three additional transvaginal ultrasound examinations
      until 32 weeks' gestation. At each examination, the mean of three measurements
      was calculated. Statistical analyses were done by t test, analysis of variance,
      and logistic regression, with significance set at P <.05. RESULTS: The mean +/-
      standard deviation precerclage cervical length was 27.2 +/- 10.3 mm and after
      cerclage was 34.1 +/- 9.9 mm (n = 80, P <.001, paired t test). No significant
      association was found (r = -0.26) between the difference in cervical length
      (postcerclage - precerclage lengths) and pregnancy outcome. Patients with a
      prophylactic cerclage had a mean cervical length that was consistently longer in
      patients delivering at term compared with those who delivered preterm at 20 to 32
      weeks' gestation. In the urgent cerclage group a significant difference in
      cervical length between those who delivered at term compared with preterm was
      evident only at 28 to 32 weeks. CONCLUSION: The increase in cervical length after
      cerclage is not predictive of term delivery. Serial cervical length measurements
      in the late second or early third trimester predict preterm birth but could
      provide earlier warning in patients with a prophylactic cerclage than in patients
      with urgent cerclage.

PMID- 10960625
TI  - A prospective population-based study of menopausal symptoms.
AB  - OBJECTIVE: To identify symptoms that change in prevalence and severity during
      midlife and evaluate their relationships to menopausal status, hormonal levels,
      and other factors. METHODS: In a longitudinal, population-based study of 438
      Australian-born women observed for 7 years with an 89% retention rate, 172
      advanced from premenopause to perimenopause or postmenopause. Annual measures
      included a 33-item symptom check list; psychosocial, lifestyle, and health
      related factors; menstrual status; hormone usage; and blood levels of follicle
      stimulating hormone and estradiol (E2). RESULTS: Increasing from early to late
      perimenopause were the number of women who reported five or more symptoms (+14%),
      hot flushes (+27%), night sweats (+17%) and vaginal dryness (+17%) (all P <.05).
      Breast soreness-tenderness decreased with the menopausal transition (-21%).
      Trouble sleeping increased by +6%. The major change in prevalence was from early
      to late perimenopause, except for insomnia, which showed a gradual increase.
      Those variables most related to onset of hot flushes were number of symptoms at
      early perimenopause (P <.05), having an unskilled or no occupation (P <.05), more
      than 10 pack-years of smoking (P <.01), and decreased E2 (P <.01). The onset of
      night sweats increased with the change in E2 (P <.05). The onset of vaginal
      dryness decreased with more years of education (P <.05). Trouble sleeping was
      predicted by prior lower well-being (P <.01), belief at baseline that women with
      many interests hardly notice menopause (P <.01), and hot flushes (P <.01).
      CONCLUSION: Although middle-aged women are highly symptomatic, the symptoms that
      appear to be specifically related to hormonal changes of menopausal transition
      are vasomotor symptoms, vaginal dryness, and breast tenderness. Insomnia
      reflected bothersome hot flushes and psychosocial factors.

PMID- 10960627
TI  - Vaginal bleeding in postmenopausal women taking low-dose norethindrone acetate
      and ethinyl estradiol combinations. The FemHRT Study Investigators.
AB  - OBJECTIVE: To determine the effect of continuous combined treatment with
      norethindrone acetate and ethinyl estradiol (E2) on vaginal bleeding, spotting,
      or bleeding and/or spotting in postmenopausal women. METHODS: Two randomized
      clinical trials were conducted in which participants recorded information on the
      daily occurrence of vaginal bleeding or spotting. In study 1, 219 postmenopausal
      women reporting at least ten hot flushes per week were randomized to placebo or
      one of four treatment groups (0.2 mg norethindrone acetate/1 microg ethinyl E2,
      0.5 mg norethindrone acetate/2.5 microg ethinyl E2, 1 mg norethindrone acetate/5
      microg ethinyl E2, or 1 mg norethindrone acetate/10 microg ethinyl E2). In study
      2, 266 postmenopausal women reporting at least 56 moderate to severe hot flushes
      were randomized to placebo or one of three treatment groups (0.5 mg norethindrone
      acetate/2.5 microg ethinyl E2, 1 mg norethindrone acetate/5 microg ethinyl E2, or
      1 mg norethindrone acetate/10 microg ethinyl E2). The total duration of treatment
      was 16 weeks in study 1 and 12 weeks in study 2. In both studies, subjects
      reported in daily diaries whether they had either bleeding or spotting. RESULTS:
      In study 1, there was a significantly greater relative risk (RR) for bleeding in
      the group receiving 1 mg norethindrone acetate/10 microg ethinyl E2 at study
      weeks 4 and 8 (RR = 1.36 and 95% confidence interval [CI] 1.01, 1.83; RR = 1.37
      and 95% CI 1.1, 1.72; respectively) compared with placebo, but not at study weeks
      12 or 16. The group receiving 1 mg norethindrone acetate/5 microg ethinyl E2 also
      had a significantly greater risk at weeks 4 and 8 (RR = 1.5 and 95% CI 1.15,
      1.96; RR = 1.33 and 95% CI 1.00, 1.77; respectively), whereas the other dose
      combinations did not differ from placebo. Results from study 2 were similar to
      those of study 1. CONCLUSION: Although there was a greater risk for bleeding
      and/or spotting at the higher doses of norethindrone acetate and ethinyl E2, this
      risk declined over time. If compliance with hormone replacement therapy regimens
      is influenced at least in part by vaginal bleeding, the combined norethindrone
      acetate/ethinyl E2 regimen investigated in these studies may provide a treatment
      option.

PMID- 10960626
TI  - Raloxifene and estrogen effects on quality of life in healthy postmenopausal
      women: a placebo-controlled randomized trial.
AB  - OBJECTIVE: To assess the effects of raloxifene, estrogen, and placebo on quality
      of life in healthy, asymptomatic, postmenopausal women. METHODS: In a
      multicenter, double-blind, 12-month study, 398 women were assigned randomly to
      one of four groups: raloxifene HCl, 60 (n = 97) or 150 mg/day (n = 100);
      conjugated equine estrogens, 0. 625 mg/day (n = 96); or placebo (n = 105). The
      Women's Health Questionnaire, a validated quality-of-life instrument for
      perimenopausal and postmenopausal women, was administered at baseline and 3-month
      intervals. RESULTS: Overall, quality of life from baseline to end point was
      preserved equally in all treatment groups. Six domains (depressed mood, somatic
      symptoms, memory/concentration, sexual behavior, sleep problems, and perceived
      attractiveness) were unchanged in all groups. Three domains (menstrual symptoms,
      vasomotor symptoms, and anxiety/fears) were statistically significantly different
      among groups. Mean scores for menstrual symptoms significantly worsened and
      vasomotor symptoms significantly improved from baseline to end point in the
      estrogen group. Mean scores for vasomotor symptoms did not worsen at any point in
      the raloxifene 60 mg/day group. Mean anxiety/fears scores improved significantly
      during raloxifene 60 mg/day administration throughout treatment (P <.05),
      irrespective of previous hormone replacement therapy, baseline estradiol (E2)
      levels, or years postmenopause. CONCLUSION: Most quality-of-life domains were not
      affected by treatment with estrogen or raloxifene. Estrogen provided relief from
      vasomotor symptoms but caused menstrual symptoms. Raloxifene 60 mg/day improved
      anxiety levels in postmenopausal women.

PMID- 10960629
TI  - Office systems intervention to improve diethylstilbestrol screening in managed
      care.
AB  - OBJECTIVE: To examine the effectiveness of a comprehensive office systems
      intervention for improving identification of diethylstilbestrol (DES) exposure, a
      low-incidence condition with potentially severe consequences. METHODS: We
      developed a comprehensive office systems intervention to facilitate screening and
      follow-up for women exposed to DES in utero, consisting of a DES toolkit and the
      clinical and administrative education necessary to use the tools effectively. The
      intervention was implemented in the internal medicine and obstetrics-gynecology
      departments at six free-standing health centers in a Boston-area staff-model
      health maintenance organization. Intervention sites were matched and paired with
      a comparison group of centers. Intervention effectiveness was assessed through
      pretest and posttest surveys of clinicians, medical record review of 3900 women,
      and review of a computerized medical records data base. RESULTS: There was
      significantly higher DES awareness and knowledge among clinical staff at
      intervention sites. Documentation of DES exposure in the medical record ranged
      from 1.14 to 2.31 times greater at intervention sites than in matched comparison
      sites, and rates of DES code use in pregnancy were 1.91 to 3.61 times greater.
      CONCLUSIONS: The office systems intervention improved documentation of DES
      exposure in a managed care environment. Because this approach was designed to
      accommodate the limited time allotted for each patient visit, it not only
      improved DES screening but could also serve as a model for integrating screening
      for other low-prevalence but potentially serious conditions into routine care.

PMID- 10960628
TI  - Norethindrone acetate and estradiol-induced endometrial hyperplasia.
AB  - OBJECTIVE: To identify the lowest effective continuous dose of norethindrone
      acetate that significantly reduces 12-month incidence of endometrial hyperplasia
      associated with unopposed 17beta-estradiol (E2), 1 mg. METHODS: In a double
      masked, randomized, multicenter study, 1176 healthy postmenopausal women 45 years
      of age or older without evidence of endometrial abnormalities were given 12
      months of treatment with unopposed E2, 1 mg, or continuous-combined regimens of
      E2, 1 mg, and norethindrone acetate, 0.1 mg, 0.25 mg, or 0.5 mg. Endometrial
      histology was evaluated at the end of the treatment period. RESULTS: Continuous
      combined E2-norethindrone acetate regimens significantly reduced 12-month
      incidence of endometrial hyperplasia compared with unopposed E2 1 mg (P <.001).
      Endometrial hyperplasia occurred in 14.6% of women treated with unopposed E2 1
      mg, whereas in all continuous-combined groups, the rate decreased to less than
      1%. Among patients who received E2-norethindrone acetate 0.1 mg, incidence was
      0.8%; among those who received 0.25 mg and 0.5 mg, it was 0.4%. CONCLUSION:
      Continuous norethindrone acetate at doses as low as 0.1 mg combined with E2 1 mg
      effectively negated risk for endometrial hyperplasia associated with unopposed E2
      1 mg, at least for the first year of therapy.

PMID- 10960630
TI  - HLA-DQB1 and HLA-DPB1 genotypes in severe preeclampsia.
AB  - OBJECTIVE: To clarify whether there are susceptible HLA-DQB1 or HLA-DPB1 alleles
      in women with preeclampsia. METHODS: The frequency of HLA-DQB1 and HLA-DPB1
      alleles was analyzed in 47 women with previous severe preeclampsia and compared
      with that in 85 normal fertile women. The types of HLA-DQB1 and HLA-DPB1 alleles
      were assessed using a polymerase chain reaction-restriction fragment length
      polymorphism method. RESULTS: The frequency of HLA-DQB1*04 allele in previously
      preeclamptic women was 21.3% (20 of 94 loci) and in the controls was 11.2% (19 of
      170 loci). Thus, the HLA-DQB1*04 allele frequency was significantly higher in
      preeclamptic women compared with controls (P <.05 by chi(2) test, OR 2.15, 95%
      confidence interval 1.08, 4.27). The frequency of other HLA-DQB1 alleles and all
      HLA-DPB1 alleles was not significantly different between groups. The incidence of
      homozygosity of HLA-DQB1 or HLA-DPB1 alleles in preeclamptic women was not
      significantly different compared with that of normal fertile women. CONCLUSION:
      These data suggest that women who have the HLA-DQB1*04 allele might be
      susceptible to preeclampsia.

PMID- 10960631
TI  - Serum levels of activin A and inhibin A and the subsequent development of
      preeclampsia.
AB  - OBJECTIVE: To determine whether serum levels of activin A and inhibin A are
      altered in patients before development of preeclampsia. METHODS: Blood samples
      were collected from patients during the second trimester of prenatal care. We
      identified patients who subsequently developed preeclampsia and matched them with
      patients who had no evidence of preeclampsia during their gestation. Matching
      criteria included gestational age at blood sampling, gestational age at delivery,
      and birth weight. Assays were then performed to assess the levels of activin A
      and inhibin A in the control and study groups. A power calculation determined
      that 12 patients who subsequently developed preeclampsia, if matched with
      controls in a 1:2 ratio, would allow the detection of differences in analyte
      levels that were 60% as large as those previously reported between patients
      already diagnosed with preeclampsia and matched controls. RESULTS: Twelve
      patients with preeclampsia were identified and matched with 24 controls. No
      differences in serum levels of activin A or inhibin A were detected between the
      two groups. Because of the significant overlap of analyte levels between the two
      groups, no cutpoint that would allow identification of patients destined to
      become preeclamptic could be determined. CONCLUSION: These data suggest that
      activin A and inhibin A cannot be used as markers for later development of
      preeclampsia in a low-risk population.

PMID- 10960632
TI  - Increased L-citrulline/L-arginine plasma ratio in severe preeclampsia.
AB  - OBJECTIVE: To evaluate nitric oxide (NO) production in patients with pregnancy
      induced hypertension or preeclampsia and in controls. METHODS: Four groups of
      pregnant women were included: 17 patients with pregnancy-induced hypertension,
      ten with mild or moderate preeclampsia, 17 with severe preeclampsia, and 44
      normotensive women matched for weeks of gestation at blood sampling with the
      cases. Plasma levels of L-citrulline and L-arginine were measured by using high
      performance liquid chromatography. RESULTS: The mean plasma levels of L
      citrulline and the ratio of L-citrulline to L-arginine, which reflects NO
      production, were higher in women with severe preeclampsia than in controls,
      patients with pregnancy-induced hypertension, and patients with mild or moderate
      preeclampsia. CONCLUSION: Nitric oxide production is enhanced in severe
      preeclampsia, possibly as a compensatory phenomenon for the increased synthesis
      and release of vasoconstrictors and platelet-aggregating agents.

PMID- 10960633
TI  - Risk for one or two very low birth weight twins: a population study.
AB  - OBJECTIVE: To calculate the frequencies of very low birth weight (VLBW) neonates
      among twins in a large population database. METHODS: The database comprised
      12,567 live-born twin pairs delivered from 1993 to 1998 in Israel. Low birth
      weight (LBW) and VLBW were defined as less than 2500 and 1500 g, respectively. We
      counted the number of pairs with VLBW neonates in three combinations: VLBW-VLBW,
      VLBW-LBW, and VLBW-over 2500 g. We compared the subsets of nulliparas and
      multiparas and the frequency of like- versus unlike-sex twins. RESULTS: The
      frequency of at least one VLBW twin was significantly higher among nulliparas
      than multiparas (odds ratio [OR] 2.3; 95% confidence interval [CI] 2.1, 2.6; P
      <.001). For pairs with VLBW-VLBW and VLBW-LBW combinations, a significantly
      higher frequency was found among nulliparas than multiparas (OR 2.0; 95% CI 1.7,
      2.8; P <.001 and OR 2.6; 95% CI 2.2, 3.1; P <.001, respectively). The risk seemed
      to be accentuated in like-sex twins. Overall, the risk of having at least one
      VLBW infant was 1:5 among nulliparas and 1:12 among multiparas. The risk of
      having two VLBW twins among nulliparas (1:11) was double that of multiparas
      (1:22). CONCLUSION: Nulliparas are at significantly increased risk of delivering
      one or two VLBW twins.

PMID- 10960634
TI  - Increased risk of cervical disease among human immunodeficiency virus-infected
      women with severe immunosuppression and high human papillomavirus load(1).
AB  - OBJECTIVE: To investigate human papillomavirus (HPV) genotypes, HPV DNA load, and
      behavioral and sociodemographic factors in a series of human immunodeficiency
      virus (HIV)-seropositive women, and to correlate HPV infection with cervical
      disease according to immune status. METHODS: Three hundred seven HIV-seropositive
      women were tested for the presence of HPV DNA by polymerase chain reaction (PCR)
      and Southern blot hybridization. Cervical disease was assessed using Papanicolaou
      smears, colposcopy, and biopsies when necessary. Various risk factors for
      cervical intraepithelial neoplasia (CIN) were tested using multiple logistic
      regression analysis. RESULTS: Cervical disease was diagnosed in 83 (27.0%) of 307
      women and HPV infection in 162 (52.8%). High HPV load (as detectable by Southern
      blot hybridization) was found in 90 (55.6%) of the 162 infected women.
      Potentially oncogenic or related genotypes were detected in 74 (82.2%) of these
      90 cases. High-load HPV infection was twice as frequent in severely
      immunosuppressed women (CD4 cell count less than 200/microL) as in women with
      higher CD4 cell counts (P =.002). High-load HPV infection was associated with a
      high risk of cervical disease (adjusted odds ratio [OR] 16.8; 95% confidence
      interval [CI] 7.0, 40.3). The risk among severely immunosuppressed women was ten
      times greater than that among women with CD4 cell counts of at least 200/microL.
      Low-load HPV infection (detected by PCR only) was a risk factor for CIN in
      severely immunosuppressed women only (adjusted OR 7.4; 95% CI 1.3, 43.0).
      CONCLUSION: Immunosuppression favors cervical high-load HPV infection with
      oncogenic genotypes and its clinical expression in HIV-seropositive women.

PMID- 10960635
TI  - Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment
      and human papillomavirus testing in women with atypia on papanicolaou smears.
AB  - OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing and risk
      assessment can predict cervical intraepithelial neoplasia (CIN) 2-3 on biopsies
      in women with atypia on Papanicolaou smears. METHODS: One hundred ninety-five
      consenting women were referred for colposcopy because of atypia on Papanicolaou
      smears between September 1997 and April 1999. Before colposcopy, women completed
      risk assessments and had cervical swabs collected for HPV testing using the
      Hybrid Capture-II assay (Digene Corporation, Silver Spring, MD). Associations of
      demographic and clinical variables were assessed by chi(2) analysis, and logistic
      regression was used to assess factors associated with CIN 2-3. The cost
      effectiveness of routine colposcopy versus reflex HPV testing by either
      conventional or liquid-based Papanicolaou smear media was compared. RESULTS:
      Cervical intraepithelial neoplasia was diagnosed in 70 of 195 women (35.9%), 55
      (28.2%) with CIN 1 and 15 (7.7%) with CIN 2-3. High-risk HPV types were detected
      in 31.3% of all subjects, 36.4% of those with CIN 1, and 93.3% of those with CIN
      2-3. By logistic regression, CIN 2-3 was associated only with detection of high
      risk HPV (odds ratio 110.08, 95% confidence interval 8.35, 999. 00). The
      sensitivity of high-risk HPV for detecting CIN 2-3 was 93. 3%, specificity 73.9%,
      positive predictive value 23.0%, and negative predictive value 99.3%. The cost of
      reflex HPV testing using conventional smear or liquid-based media was less than
      routine colposcopy ($4809 and $4308, respectively, versus $4875 per case
      detected). CONCLUSIONS: Triage based on HPV testing would result in referral of
      approximately 31% of patients to colposcopy and appears to be a sensitive and
      cost-effective alternative to colposcopy.

PMID- 10960636
TI  - Absence of estrogen receptor-beta expression in metastatic ovarian cancer.
AB  - OBJECTIVE: To evaluate the expression of estrogen receptor (ER)alpha and ERbeta
      mRNA and protein in normal ovarian tissue and primary and metastatic tumors.
      METHODS: Estrogen receptor alpha and ERbeta expression was studied in normal
      ovarian biopsies (n = 9) and primary (n = 8) and metastatic ovarian epithelial
      cancers (n = 8). Ovarian tissue was collected from surgical samples. Estrogen
      receptor alpha and ERbeta mRNA expression was compared by coamplification of the
      mRNA of the ERs. Expression was confirmed at the protein level by Western blot
      analysis using antibodies specific for each receptor. RESULTS: Among eight
      primary ovarian cancer samples, three had only ERalpha, two had only ERbeta, and
      three had both. All eight metastatic ovarian cancer tissues expressed only
      ERalpha mRNA and protein. Biopsies from normal ovaries had ERalpha and ERbeta
      mRNA and protein. Two of the ovarian epithelial cancer samples were paired and
      showed the same results. CONCLUSION: We found varying amounts of ERalpha and
      ERbeta in normal ovaries, lower levels of ERbeta expression in ovarian epithelial
      cancer primary tumors, and only ERalpha in metastatic tumors. Our findings
      indicate that a fundamental difference might exist between primary and metastatic
      cells, which could be caused by intrinsic or extrinsic factors that regulate ER
      gene expression.

PMID- 10960637
TI  - Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted
      peptide-pulsed autologous dendritic cells.
AB  - OBJECTIVE: To evaluate the potential of dendritic cells pulsed with acid-eluted
      peptides derived from autologous ovarian cancer cells for eliciting a tumor
      specific cytotoxic T cell response in women with advanced ovarian cancer.
      METHODS: CD8+ T lymphocytes derived from peripheral blood mononuclear cells
      stimulated in vitro with autologous ovarian tumor peptide-pulsed dendritic cells
      were tested for their ability to induce an HLA class I-restricted cytotoxic T
      lymphocyte response against autologous tumor cells. To correlate cytotoxic
      activity by cytotoxic T lymphocytes with T cell phenotype, we used two-color flow
      cytometric analysis of surface markers and intracellular cytokine expression
      (interferon-gamma versus interleukin-4). RESULTS: CD8+ cytotoxic T lymphocyte
      responses against autologous ovarian tumor cells were elicited in three
      consecutive women who had advanced ovarian cancer. Although cytotoxic T
      lymphocyte populations from all women expressed strong cytolytic activity against
      autologous tumor cells, they did not lyse autologous lymphoblasts or Epstein-Barr
      virus-transformed cell lines, and they showed negligible cytotoxicity against the
      natural killer-sensitive cell line K-562. Cytotoxicity against the autologous
      tumor cells was significantly inhibited by anti-HLA class I (W6/32) and anti-HLA
      A2 (BB7-2) monoclonal antibodies. CD8+ cytotoxic T lymphocytes expressed variable
      levels of CD56 and preferentially expressed interferon-gamma rather than
      interleukin-4. CONCLUSIONS: Peptide-pulsed dendritic cells induced specific CD8+
      cytotoxic T lymphocytes that killed autologous tumor cells from women with
      advanced ovarian cancer. This finding might contribute to the development of
      active or adoptive immunotherapy for residual or resistant ovarian cancer after
      standard surgery and cytotoxic treatment.

PMID- 10960638
TI  - Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and
      epithelium.
AB  - OBJECTIVE: To identify the effects of depomedroxyprogesterone acetate (DMPA) on
      vaginal microbial flora and epithelium. METHODS: Women who desired DMPA for
      contraception were evaluated before and at 3 and 6 months after initiation of 150
      mg DMPA injections every 3 months. At each visit, we assessed genital symptoms,
      vaginal signs, vaginal microflora, and histopathology by vaginal biopsies.
      RESULTS: Among 38 women observed for 6 months, there was significant reduction in
      mean serum estradiol level (99.9 +/- 9.3 pg/mL to 26.6 +/- 1.6 pg/mL, P <.001).
      The number of subjects with any Lactobacillus did not change, but the number with
      hydrogen peroxide (H(2)O(2))-positive Lactobacillus decreased from 20% before to
      12% after 6 months of DMPA (P =.005). The log concentration in colony-forming
      units per milliliter of vaginal fluid of H(2)O(2)-positive Lactobacillus
      decreased in a linear manner from 4. 0 +/- 0.6 at baseline to 2.5 +/- 0.6 after 6
      months of DMPA use (P =. 006). The mean number of cell layers in the epithelium
      was reduced slightly from 28.1 +/- 0.7 to 25.9 +/- 0.9 (P =.05), epithelial
      thickness decreased from 1.02 +/- 0.04 mm to 0.89 +/- 0.05 mm (P =. 005), and the
      glycogen-positive thickness decreased from 0.81 +/- 0. 04 mm at baseline to 0.66
      +/- 0.05 after 6 months of DMPA use (P =. 005). CONCLUSION:
      Depomedroxyprogesterone acetate produced a systemic hypoestrogenic state
      associated with decreased H(2)O(2)-positive Lactobacillus colonization and slight
      thinning of the glycogen vaginal epithelial layer. Such changes possibly
      compromise the vaginal barrier to infection.

PMID- 10960639
TI  - Obstetric risk factors for stress urinary incontinence: a population-based study.
AB  - OBJECTIVE: To evaluate obstetric and maternal risk factors for stress urinary
      incontinence. METHODS: We linked three national, Swedish, population-based
      registries with the use of unique personal identification numbers. All women born
      between 1932 and 1977 and operated on for stress urinary incontinence between
      1987 and 1996 were identified from the Hospital Discharge Registry. This
      information was linked with the Medical Birth Registry (for the years 1973-1995),
      containing information on antenatal care, delivery, and the newborn, and the
      Fertility Registry (for the years 1932-1997), containing information on the
      number of children delivered by each Swedish woman. For determination of odds
      ratios (ORs) and approximate 95% confidence intervals (CIs), we used the Mantel
      Haenszel method and a test-based method after suitable stratifications and
      exclusions. RESULTS: Diabetes mellitus, body mass index (BMI), age at first
      delivery, parity, birth weight, and epidural analgesia were positively associated
      with incontinence surgery. In contrast, cesarean delivery, forceps/vacuum
      extraction, and episiotomy were negatively associated with incontinence surgery.
      No association was found between surgery for stress incontinence and age at last
      delivery, smoking during pregnancy, level of education, multiple birth, large
      perineal tear, or breech presentation at any vaginal delivery. The OR for
      incontinence surgery was similarly decreased for nulliparous women and for
      uniparous women delivered by elective cesarean. CONCLUSION: Vaginal delivery,
      notably the first, is strongly associated with later surgery for stress
      incontinence, but the association is modified by maternal conditions and
      interventions during delivery. No association was found between surgery for
      stress incontinence and pregnancy per se.

PMID- 10960640
TI  - Risk factors for lower urinary tract symptoms in women 40 to 60 years of age.
AB  - OBJECTIVE: To determine the relationship between lower urinary tract symptoms and
      possible associated risk factors in women 40-60 years old. METHODS: In a normal
      population study, 502 women with lower urinary tract symptoms and 742 women with
      no symptoms (controls) were asked about possible associated factors. RESULTS:
      Four hundred eighty-seven women (97.0%) with symptoms and 564 controls (76.0%)
      completed the study. Stress incontinence was associated with parity (primipara
      odds ratio [OR] 2.2, 95% confidence interval [CI] 1.0, 4. 9; para 2 OR 3.9, 95%
      CI 1.9, 8.0; para 3 OR 4.5, 95% CI 2.1, 9.5), use of diuretics (OR 2.2, 95% CI
      1.2, 3.9), hysterectomy (OR 2.4, 95% CI 1.6, 3.7), and increased body mass index
      (BMI). Urge incontinence was associated with use of diuretics (OR 4.0, 95% CI 2.
      2, 7.1) and BMI. Urgency was associated with parity (primipara OR 1. 9, 95% CI
      0.9, 4.2; para 2 OR 3.0, 95% CI 1.5, 5.9; para 3 OR 3.1, 95% CI 1.5, 6.5), use of
      diuretics (OR 2.7, 95% CI 1.5, 4.7) and BMI. Associations between non
      incontinence symptoms (except urgency) and observed factors were weak and
      inconsistent. Straining at stool and constipation were inversely associated with
      lower urinary tract symptoms. Overall, lesion of sphincter ani, episiotomy, fetal
      weight, physical activity, and hormonal status had minor association with lower
      urinary tract symptoms. CONCLUSION: Lower urinary tract symptoms were associated
      positively with parity, BMI, prior hysterectomy, use of diuretics, straining at
      stool, and constipation.

PMID- 10960641
TI  - Contrast-enhanced, three-dimensional power Doppler sonography for differentiation
      of adnexal masses.
AB  - OBJECTIVE: To investigate the potential usefulness of contrast-enhanced, three
      dimensional power Doppler sonography in the differentiation of benign and
      malignant adnexal lesions. METHODS: A total of 45 patients with complex adnexal
      lesions of uncertain malignancy at transvaginal B mode and/or color Doppler
      sonography were prospectively evaluated with three-dimensional power Doppler
      sonography before and after injection of contrast agent. Presence of a
      penetrating pattern and a mixed penetrating and peripheral pattern suggested
      adnexal malignancy. All the results were compared with histopathology. RESULTS:
      There were 12 cases of ovarian malignancy and 33 benign adnexal lesions. Of the
      12 ovarian cancers, seven (58. 3%) showed vascular distribution suggestive of
      malignancy at nonenhanced three-dimensional power Doppler sonography. After
      injection of contrast agent, a penetrating vascular pattern and/or a mixed
      penetrating and peripheral pattern were detected in all cases of ovarian
      malignancy. One cystadenofibroma demonstrated penetrating vessels at initial
      scan, whereas two benign lesions (fibroma and cystadenofibroma) were misdiagnosed
      as malignant at contrast-enhanced, three-dimensional power Doppler sonography.
      The use of a contrast agent with three-dimensional power Doppler sonography
      showed diagnostic efficiency (95.6%) that was superior to that of nonenhanced
      three-dimensional power Doppler sonography (86. 7%). CONCLUSION: Contrast
      enhanced, three-dimensional power Doppler sonography provides better
      visualization of tumor vascularity in complex adnexal masses. If used together
      with three-dimensional morphologic ultrasound assessment, enhanced three
      dimensional power Doppler imaging might precisely discriminate benign from
      malignant adnexal lesions.

PMID- 10960642
TI  - After-hours telephone calls to obstetrician-gynecologists.
AB  - OBJECTIVE: To characterize the pattern, content, and management of after-hours
      telephone interactions between obstetrician-gynecologists and patients. METHODS:
      In a prospective observational study, 12 resident and nine private physicians
      practicing obstetrics and gynecology completed data cards for after-hours
      telephone interactions with patients. Chief complaints were categorized as
      related to either women's health or primary care and on whether women were
      pregnant, postpartum, or not pregnant. Triage dispositions (evaluate now, office
      follow-up, or home care) were compared between groups. Women also were asked what
      they would have done if they had been unable to contact their physicians by
      telephone. RESULTS: One hundred ninety-two of 276 calls evaluated (69. 6%) were
      from pregnant women, 20 (7.2%) were from postpartum women, and 64 (23.3%) were
      from nonpregnant women. Calls were related to primary care health issues in 24.1%
      (n = 45) of pregnant women, 40% (n = 8) of postpartum women, and 28.1% (n = 18)
      of nonpregnant women. There were no differences between residents and private
      physicians in the proportion of women triaged to immediate evaluation for
      pregnancy (35.1% [n = 40] versus 41.9% [n = 31], P =.74) or postpartum (11.1% [n
      = 1] versus 10% [n = 1],P =.96) problems. Among 139 women triaged to office
      follow-up, 41% (n = 57) would have come to the hospital for emergency evaluation
      if they had been unable to reach their physicians. CONCLUSION: Resident and
      private obstetrician-gynecologists provide primary care and women's health care
      advice during after-hours telephone calls from patients. More than one third of
      after-hours telephone calls from pregnant women are triaged to immediate
      evaluation.

PMID- 10960643
TI  - Oral misoprostol and intracervical dinoprostone for cervical ripening and labor
      induction: a randomized comparison.
AB  - OBJECTIVE: To compare efficacy, safety, and tolerance of oral misoprostol with
      intracervical dinoprostone for cervical ripening and labor induction. METHODS:
      Two hundred women were randomized to receive single doses of oral misoprostol 200
      microg or 0.5 mg of dinoprostone intracervically every 6 hours for a maximum four
      doses. RESULTS: The intervals from administration of the drug to active phase of
      labor (11.1 hours [7-24] versus 15.8 hours [7.5-29.62], P =. 01), to delivery
      (14.0 hours [8.42-27.61] versus 20.2 hours [16.7-32. 8], P =.01), and to rupture
      of membranes (10.0 hours [4.95-24.7] versus 15.6 hours [8.2-29.2], P =.003) were
      significantly shorter in the misoprostol group. All those variables were not
      distributed normally, so results are presented as median and interquartile range.
      The rates of women who needed oxytocin (68% versus 52%, P =.03) and cesarean for
      failed induction (9% versus 1%, P =.01) were higher in the dinoprostone group.
      CONCLUSION: A single dose of 200 microg oral misoprostol was more effective for
      cervical ripening and labor induction than 0.5 mg of dinoprostone intracervically
      every 6 hours, with a maximum of four doses.

PMID- 10960644
TI  - Spontaneous regression of vulvar intraepithelial neoplasia 2-3.
AB  - OBJECTIVE: To determine the background and clinical features of a group of women
      who experienced spontaneous regression of vulvar intraepithelial neoplasia (VIN)
      2-3 before treatment was undertaken. METHODS: A retrospective review was made of
      the records of 14 women who experienced spontaneous regression of VIN 2-3.
      RESULTS: The women were 15-27 years of age (median 19.5 years). Ninety-three
      percent were non-white. All women were seen initially in a sexual health clinic,
      and with one exception, all had been treated previously for genital condyloma
      acuminata. Four of the 14 cases were pregnancy-associated. Half of the women were
      asymptomatic. The transit time to regression of VIN 2-3 was 3-30 months (median
      9.5 months). The median follow-up was 3 years. All lesions were multiple and
      pigmented. CONCLUSION: Spontaneous regression of VIN 2-3 can occur in young women
      with multifocal pigmented lesions.

PMID- 10960645
TI  - Health-related consequences of physical and sexual violence: women in the
      military.
AB  - OBJECTIVES: To identify differences in health-related quality of life among women
      veterans who were raped, physically assaulted (not in the context of rape or
      domestic violence), both, or neither during military service. METHODS: We did a
      cross-sectional telephone survey of a national sample of 558 women veterans who
      served in Vietnam and subsequent eras of military service. A stratified survey
      design selected subjects according to era of service and location. The interview
      included socioeconomic information, lifetime violence history, the Women's
      Military Environment Survey to assess women's military experiences, and the
      Medical Outcomes Study Short Form-36 to assess health-related quality of life.
      RESULTS: Five hundred thirty-seven women completed the interview. Half (48%)
      experienced violence during military service, including rape (30%), physical
      assault (35%), or both (16%). Women who were raped or dually victimized were more
      likely to report chronic health problems, prescription medication use for
      emotional problems, failure to complete college, and annual incomes less than
      $25,000 (P <.05). Women who were physically assaulted or raped reported
      significantly lower health-related quality of life (P <.05). Those who had both
      traumas reported the most severe impairment, comparable to women with chronic
      illnesses. CONCLUSION: This study suggests that the sequelae of violence against
      women are an important public health concern. More than a decade after rape or
      physical assault during military service, women reported severely decreased
      health-related quality of life, with limitations of physical and emotional
      health, educational and financial attainment, and severe, recurrent problems with
      work and social activities.

PMID- 10960646
TI  - Modulation of perceived contrast by a moving surround.
AB  - The apparent contrast of a center pattern depends on the contrast of its
      surround. To examine the suprathreshold perception of moving patterns, we
      measured the perceived contrast of a moving grating while the direction and speed
      of the surround patterns varied. Subjects matched the apparent contrast of a
      center patch embedded in surround patches to that of a patch with no surround
      pattern. Temporal frequency, Michelson contrast and movement direction of both
      center and surround patterns varied systematically. We found that: (1) contrast
      reduction is most prominent when the center and surround have the same velocity
      (velocity selectivity); (2) contrast enhancement occurs when the surround moves
      at a higher speed than the center, if the difference in temporal frequencies of
      center and surround exceeds 10-20, independent of the directional relationship
      between center and surround; (3) contrast reduction is stronger for higher
      surround contrasts with lower center contrasts; and (4) contrast enhancement is
      relatively unaffected by center and surround contrasts. We conclude that the
      contrast perception of moving patterns is influenced by directionally-selective
      mechanisms except at high temporal frequencies. Our results further suggest that
      there is not only the lateral inhibition often assumed to influence contrast gain
      control, but also an excitatory connection between motion encoding units.

PMID- 10960647
TI  - Inter-attribute tilt effects and orientation analysis in the visual brain.
AB  - A test grating appears to be tilted away from an inducing grating for small
      angular separations (repulsion), but towards the inducing grating for larger
      angular separations (attraction). Previous research on luminance gratings
      suggests that repulsion is caused by local inhibition in cortical areas V1 and/or
      V2, and that the attraction involves global interactions beyond V1, in
      extrastriate areas. Experiments reported here demonstrate attribute invariant
      attraction and repulsion effects for gratings specified by luminance, motion, and
      disparity contrasts. A frame surrounding the inducing grating abolishes only the
      attraction effect, but a spatial frequency difference, or a small gap between the
      inducer and test gratings, abolishes only the repulsion effect, irrespective of
      the attributes that specify the gratings. It is proposed that detectors
      selectively sensitive to attribute invariant orientation and size exist in early
      cortical sites such as V1 and/or V2.

PMID- 10960648
TI  - Determinants of object recognition.
AB  - We demonstrate that performance on an object recognition task can be explained in
      terms of observer-specific perceptual profiles. These profiles are derived from a
      battery of tests, including the effects of stereo, texture, outline (occluding
      contour), and motion cues on amplitude judgements of curved surfaces. Using a
      task in which observers learned to recognise 'amoeboid' objects, a multivariate
      regression analysis revealed that three psychometric variables derived from the
      test battery account for 74% of the variance in learning rate. These variables
      are choice reaction time, and the relative dependence of amplitude judgements on
      motion and outline cues. The implications of these findings for the existence of
      observer-specific perceptual profiles, and their relation to the fundamental
      psychophysical competences associated with object recognition are discussed.

PMID- 10960649
TI  - Normalization: contrast-gain control in simple (Fourier) and complex (non
      Fourier) pathways of pattern vision.
AB  - Results from two types of texture-segregation experiments considered jointly
      demonstrate that the heavily-compressive intensive nonlinearity acting in static
      pattern vision is not a relatively early, local gain control like light
      adaptation in the retina or LGN. Nor can it be a late, within-channel contrast
      gain control. All the results suggest that it is inhibition among channels as in
      a normalization network. The normalization pool affects the complex-channel
      (second-order, non-Fourier) pathway in the same manner in which it affects the
      simple-channel (first-order, Fourier) pathway, but it is not yet known whether
      complex channels' outputs are part of the normalization pool.

PMID- 10960650
TI  - The role of the superior colliculus in saccade initiation: a study of express
      saccades and the gap effect.
AB  - Neural mechanisms underlying the initiation of saccadic eye movements were
      studied by recording the activity of neurons in the superior colliculus of rhesus
      monkeys that had extensive experience on the gap task using targets restricted to
      one visual field. The superposition of visual activation upon the increased
      excitability occurring on gap trials facilitates the occurrence of a motor burst
      with extremely short latency; the motor burst is tightly coupled to saccade onset
      for the full range of saccadic reactions times, both regular and express. We
      found no evidence that express saccades are a special class of saccades triggered
      directly by visual responses. The low frequency activity, necessary for the
      occurrence of express saccades, neither initiates express saccades nor serves as
      an accurate predictor of the direction or latency of saccades. Based upon these
      findings, the hypothesis that the motor burst of collicular neurons serves as a
      signal for triggering saccade onset can now be extended to express saccades.

PMID- 10960651
TI  - The control of saccadic adaptation: implications for the scanning of natural
      visual scenes.
AB  - Accurate scanning of natural scenes depends on: (1) attentional selection of the
      target; (2) spatial pooling over the attended target to compute the precise
      landing position; and (3) adaptive modification of saccades to ensure saccadic
      accuracy. The present experiments studied adaptation. Adaptive modifications were
      induced by displacing the target during saccades. Adaptation was found to be: (1)
      similar for a small target point and a large target circle, despite the
      differences in the spatial pattern of landing position errors for each; (2)
      unaffected by instructions to look part way to the target, even though such
      instructions altered landing position error relative to the target; and (3)
      insensitive to symbolic cues disclosing the direction of the intra-saccadic
      displacement. Briefly delaying the presentation of the post-saccadic target
      greatly reduced adaptation. Neither corrective saccades, nor the position errors
      that trigger corrections, were involved in adaptation because corrective saccades
      rarely occurred with a large target circle even though the circle produced as
      much adaptation as the single point. Taken together, the results do not support
      the traditional notion that post-saccadic retinal position error controls
      adaptation. We propose that adaptation relies on a comparison of the actual post
      saccadic retinal image with the post-saccadic image that would be predicted based
      on a representation of the planned saccade. Such a comparison: (1) is consistent
      with our results; (2) may be more effective than retinal position error in
      controlling adaptation in natural visual scenes containing large targets and
      backgrounds; and (3) is similar to the motion-based adaptive mechanisms
      associated with the VOR. Similarity between the adaptive control of saccades and
      adaptive control of the VOR raises the possibility that the most important role
      of saccadic adaptation may be the coordination of eye and head movements during
      shifts of gaze.

PMID- 10960652
TI  - Saccadic localization of occluded targets.
AB  - Saccadic eye movements are able to localize spatially-extended targets, including
      patterns of random dots and simple shapes, with a high degree of precision
      [McGowan, Kowler, Sharma & Chubb (1998). Vision Research, 38, 895-909; Melcher &
      Kowler (1999). Vision Research, 39, 2929-2946]. This paper investigates the
      representations of object shape that guide saccades. We studied saccadic
      localization of partially-occluded triangles (two or three vertices removed) to
      find out whether saccades have access to a representation of the full shape,
      despite the missing portions. Targets were configured so that they could be seen
      either as triangles, which were partially occluded by polygons, or as fragments
      in front of the same polygons. Subjects tried to saccade to the inferred full
      triangle and a discrimination paradigm was used to evaluate their success.
      Occlusion cues were ineffective in that saccades directed to the occluded
      triangles landed near the center of the visible fragment, even when it was
      configured as a triangle behind occluders. Removing the occluders and leaving
      only three segments of the triangle (vertices removed) helped somewhat, but
      performance never resembled that achieved with either a full triangle or a 3-dot
      configuration. We conclude that the saccadic system is insensitive to at least
      some cues that can be used to infer the shape of objects. For occluded targets,
      the representation used by saccades may be closer to the configuration of the
      retinal image.

PMID- 10960653
TI  - The characteristics of dynamic overshoots in square-wave jerks, and in congenital
      and manifest latent nystagmus.
AB  - Dynamic overshoots are seen after voluntary re-fixation saccades. They are
      microsaccadic movements which follow primary saccades and have no delay. The
      purpose of this study was to examine the prevalence and metrics of the dynamic
      overshoots seen after involuntary saccades. Using infra-red oculography we
      demonstrate that dynamic overshoots are a common occurrence in physiological
      square-wave jerks, congenital nystagmus and manifest latent nystagmus and that
      these overshoots are saccadic in nature and have the same dynamic characteristics
      as those seen following voluntary saccades. It is therefore likely that they
      share common neural commands to those dynamic overshoots seen after a volitional
      saccade. All dynamic overshoots are postulated to be the unwanted consequence of
      making a saccade and are simulated in a model of fast oculomotor behaviour which
      is consistent with known experimental results.

PMID- 10960654
TI  - Three-dimensional organization of vestibular related eye movements to rotational
      motion in pigeons.
AB  - During rotational motions, compensatory eye movement adjustments must continually
      occur in order to maintain objects of visual interest as stable images on the
      retina. In the present study, the three-dimensional organization of the vestibulo
      ocular reflex in pigeons was quantitatively examined. Rotations about different
      head axes produced horizontal, vertical, and torsional eye movements, whose
      component magnitude was dependent upon the cosine of the stimulus axis relative
      to the animal's visual axis. Thus, the three-dimensional organization of the VOR
      in pigeons appears to be compensatory for any direction of head rotation.
      Frequency responses of the horizontal, vertical, and torsional slow phase
      components exhibited high pass filter properties with dominant time constants of
      approximately 3 s.

PMID- 10960655
TI  - A hierarchical neural system with attentional top-down enhancement of the spatial
      resolution for object recognition.
AB  - We present a hierarchical neurodynamical system for object recognition based on
      attentional control of the spatial resolution with which an object is analyzed
      during an iterative hypothesis testing cycle. Psychophysical evidence strongly
      suggests that attentional processing results in the enhancement of the spatial
      resolution in the input region corresponding to the focus of attention. We adopt
      a computational neuroscience approach in order to analyze this attentional
      enhancement of the spatial resolution for object recognition. The system consists
      of a where- and a what-module which include networks with feedforward and
      feedback interconnections describing the mutual links between different areas of
      the visual cortex.

PMID- 10960656
TI  - Temporal frequency deficits in the electroretinogram of the cone system in X
      linked retinoschisis.
AB  - We investigated the extent of, and basis for, abnormalities in the flicker
      electroretinogram (ERG) of the cone system of patients with X-linked
      retinoschisis (XLRS), a form of hereditary vitreoretinal degeneration. ERGs were
      recorded from six patients with XLRS and from six visually normal subjects using
      high-contrast sinusoidal flicker that ranged in temporal frequency from 8 to 96
      Hz, and that was presented against a rod-desensitizing adapting field. Compared
      to the control subjects, the patients with XLRS showed a significant reduction in
      the amplitude of the ERG response fundamental at temporal frequencies of 32 Hz
      and higher. In addition, their response phases were at or below the lower limits
      of normal (representing a phase lag) for temporal frequencies greater than 8 Hz.
      The higher harmonics of the patients' ERG responses to a low frequency stimulus
      were attenuated over the same temporal frequency range as was the response
      fundamental. This finding indicates that a major component of the abnormal
      temporal filtering responsible for the ERG abnormalities in XLRS occurs beyond
      the level of the early retinal nonlinearity that generates the harmonic
      components of the ERG response, and therefore is most likely postreceptoral in
      origin. Consistent with this interpretation, the ERG waveforms of the XLRS
      patients showed a significant attenuation of the ON-response component, with a
      normal OFF response. The overall pattern of results suggests that the marked
      reduction of ERG response amplitudes and the phase lag at the higher temporal
      frequencies in XLRS stem, at least in part, from a predominant attenuation of the
      ON-bipolar cell contribution to the flicker ERG.

PMID- 10960658
TI  - Respiratory immunology

PMID- 10960657
TI  - Inter-ocular interference and circadian regulation of the chick
      electroretinogram.
AB  - Illumination of a chick's eye allows light to pass through to the retina of the
      contralateral eye. Electroretinographic (ERG) recording employing the scalp or
      comb as a reference results in shorter implicit time, higher amplitude and lower
      sensitivity during the day than during the night in a light:dark (LD) cycle and
      in constant darkness (DD). ERG recordings employing the contralateral eye as
      reference abolishes rhythmicity or reverses the phase angle (higher amplitudes at
      night). This is probably due to light transmission through the eyes to elicit
      visual responses in the reference. The contralateral eye is a poor choice for
      reference in birds and obscures physiological analyses of clock control of
      vision.

PMID- 10960659
TI  - Introduction to the special issue of immunopharmacology

PMID- 10960660
TI  - Nitric oxide, peroxynitrite, and lower respiratory tract inflammation.

PMID- 10960661
TI  - Lymphocyte-endothelial cell adhesive interactions in lung immunity: lessons from
      the murine response to particulate antigen.
AB  - The adhesive interaction between lymphocytes and lung endothelial cells presents
      an attractive arena for the development of novel therapeutic agents to modify
      pathologic pulmonary immune responses. The conceptual basis for choosing
      molecular targets to modulate this adhesive interaction derives, in large part,
      from results of murine experimental model systems of the pulmonary immune
      response. This article reviews one such model, the response of primed C57BL/6
      mice to the particulate antigen sheep erythrocytes. Novel data are presented on
      the effect of a blocking anti-alpha(4) integrin monoclonal antibody on lung
      leukocyte and lymphocyte subset accumulation after intratracheal (IT) antigen
      challenge. Results from this model system have indicated that lymphocytes may use
      either the endothelial selectins or alpha(4) integrin as independent pathways to
      initiate recruitment into the lungs.

PMID- 10960662
TI  - Leukocyte recruitment during pulmonary Cryptococcus neoformans infection.
AB  - Leukocyte recruitment to the site of infection by the encapsulated yeast
      Cryptococcus neoformans is critical for clearance of the infection. We review
      data from our lab that chemokines, such as the CC chemokines MCP-1 and MIP
      1alpha, are important mediators of leukocyte recruitment during C. neoformans
      infection. In addition, studies in CC chemokine receptor knockout mice have
      demonstrated that CCR2 and CCR5 are required not only for leukocyte recruitment
      but also for other aspects of immune response development and innate imunity to
      C. neoformans.

PMID- 10960663
TI  - Immune-mediated disease pathogenesis in respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is an important cause of severe respiratory
      disease in persons at both extremes of age. Wheezing is a cardinal sign of
      infection and the illness is associated with an increased incidence of childhood
      asthma. Data from both humans and animal models have linked severe disease in
      infants and the syndrome of vaccine-enhanced illness with an aberrant composition
      of CD4+ T cells, suggestive of an exaggerated Th2 response. Studies in murine
      models have shown that prior vaccination, coexisting allergic inflammation, or
      direct modulation of the cytokine milieu can profoundly influence the immune
      response to RSV and thereby affect the expression of disease. In addition, there
      are intrinsic antigenic properties of the RSV G glycoprotein that promote Th2
      responses and eosinophilia. This paper proposes an integrated working model of
      how host and virus factors interact to determine the characteristics of RSV
      induced illness. This model suggests strategies for the development of new
      vaccine and immunotherapeutic interventions, and creates a framework for asking
      additional questions about the immunopathogenesis of RSV.

PMID- 10960664
TI  - Host pathogen interactions in Legionnaires' disease: lessons learned from a
      murine animal model.

PMID- 10960665
TI  - Genetic analysis of the Bordetella infectious cycle.

PMID- 10960666
TI  - The pathology of asthma: brief review.
AB  - The presence of chronic airway inflammation in asthmatic patients has been known
      for over a century, but the relationship of this inflammatory process to the
      pathogenesis of reversible airflow obstruction and non-specific bronchial
      hyperresponsiveness remains unclear. In recent years, the increasing ability to
      sample the lower respiratory tract of living asthmatic patients, coupled with
      revolutionary advances in immunology and molecular biology, has resulted in
      extensive evaluation of inflammatory cells and mediators implicated in the
      pathogenesis of asthma. In addition, there is increasing recognition that airway
      remodeling, characterized by thickening of all compartments of the airway wall,
      may have profound consequences on the mechanics of airway narrowing in asthma and
      contribute to the chronicity and progression of the disease. In this brief
      review, I will describe the gross and microscopic pathology of asthma, the
      process of airway remodeling and its functional consequences, and speculate on
      future directions to improve our understanding of the structural changes of
      asthma and their pathogenic role.

PMID- 10960667
TI  - Murine models of asthma in understanding immune dysregulation in human asthma.

PMID- 10960669
TI  - Experimental approaches to analysis of immune dysregulation in human allergic
      disease.
AB  - Over the last 40 years, much attention has been directed towards identification
      of the immunologic, genetic and environmental factors that predispose towards
      development of allergic disease. An implicit assumption in many such studies is
      that clinical tolerance reflects from immunologic tolerance. Here we critically
      review the conceptual background and experimental data arguing for the
      alternative hypothesis that failure to develop atopic disease reflects the
      success of type 1 dominated immunity that constitutively impedes development of
      type 2 responses to environmental antigens, hence, clinical immediate
      hypersensitivity. We report that endogenous production of type 1 chemokines such
      as IP-10 by non-atopic individuals may play a substantive role in maintaining
      this putatively protective type 1 bias in non-atopic subjects. Polyclonal
      activators (superantigen TSST-1, anti-CD3, PHA) were used to activate distinct
      intracellular signaling pathways, inducing quantitatively different IFNgamma:IL-4
      ratios in primary culture of human PBMC. In parallel, physiologic stimuli such as
      grass pollen or cat antigen were used to evaluate the impact of IP-10 on CD4 T
      cell dependant, chloroquine-sensitive cytokine synthesis. IFNgamma responses by
      non-atopic subjects were markedly increased in the presence of nM concentrations
      of rhIP-10 while type 2 cytokine synthesis remained unaffected. Optimal rIP-10
      concentrations for promoting expression and maintenance of type 1 cytokine
      synthesis in vitro (0.1 to 10 ng/ml) were at or well below those generally used
      for chemotaxis (5 to 100 ng/ml). Collectively, our findings suggest a potential
      role for this T cell focused chemokine in maintaining the default type 1
      responses usually caused to environmental antigens in non-atopic subjects. These
      may play a role in determining the relative susceptibility of individuals to
      develop atopic disease. Taken together with recent reports of other roles played
      by chemokines in shaping the nature of immune responses, the data suggest that
      constitutive, endogenous type 1 chemokine synthesis may play a homeostatic role
      in inhibiting development of atopic disease.

PMID- 10960668
TI  - Immunologically mediated signaling in basophils and mast cells: finding
      therapeutic targets for allergic diseases in the human FcvarepsilonR1 signaling
      pathway.
AB  - The high affinity IgE receptor, FcvarepsilonRI, plays key roles in an array of
      acute and chronic human allergic reactions including asthma, allergic rhinitis,
      atopic dermatitis, urticaria and anaphylaxis. In humans and rodents, this
      receptor is found at high levels on basophils and mast cells where its activation
      by IgE and multivalent antigen produces mediators and cytokines responsible for
      FcvarepsilonRI-dependent acute inflammation. Mast cells can additionally
      contribute to sustained inflammatory responses by internalizing antigen bound to
      IgE-FcvarepsilonRI complexes for processing to peptides and presentation to T
      cells. In humans, the FcvarepsilonRI is also expressed, at lower density, on
      monocytes, macrophages and dendritic cells (DC) where its likely functions again
      include both signaling to mediator and cytokine production and antigen
      presentation. Our laboratories have focused on defining the earliest steps in the
      FcvarepsilonRI signaling cascade in basophils and mast cells and on developing
      new routes to control allergic inflammation based on inhibiting these events.
      Here, we describe novel strategies to limit antigen-stimulated FcvarepsilonRI
      signaling by: (1) sequestering the FcvarepsilonRI-associated protein-tyrosine
      kinase, Lyn, that initiates FcvarepsilonRI signaling; (2) eliminating; or (3)
      inactivating the protein-tyrosine kinase, Syk, that propagates FcvarepsilonRI
      signaling; and (4) establishing inhibitory crosstalk between FcvarepsilonRI and a
      co-expressed receptor, FcgammaRII, that again limits FcvarepsilonRI-mediated Syk
      activation. These strategies may form the basis for new therapies for allergic
      inflammation.

PMID- 10960670
TI  - gammadelta T-cell-deficient mice do not differ from normal controls in their
      induction or expression of type 2 dominant responses to exogenous antigen.
AB  - The roles that gammadelta T cells play in shaping initial CD4 T cell activation,
      and sensitivity to development of atopic diseases, remain controversial. Using a
      genetic knockout model of gammadelta T-cell deficiency, we investigated the role
      of these cells in initiation of exogenous antigen specific murine cytokine and
      antibody responses. Given that the most widely distributed and clinically
      prominent class of allergens are soluble protein antigens, we utilized OVA to
      examine the role played by gammadelta T cells in shaping the induction and
      expression of exogenous Ag specific immune responses. Focusing on immunization
      conditions that stimulate in vivo induction of type 2 dominant immunity, we
      report that gammadelta deficient and intact C57Bl6 mice exhibit similar OVA
      specific responses as indicated by the (i) intensity of initial T-cell activation
      (ii) the type1 vs. type 2 balance of exogenous Ag specific cytokine synthesis and
      the (iii) intensity and the relative balance of the resulting IgE vs. IgG(2a)
      responses in vivo seen in these strains. Taken together, the data are consistent
      with the hypothesis that gammadelta T cells do not play an essential role in
      shaping induction of systemic immune responses to soluble exogenous antigen in
      type 2 dominated responses.

PMID- 10960671
TI  - Stress proteins and the immune response.
AB  - The heat shock or stress response is one of the most highly conserved adaptive
      responses in nature. In single cell organisms, the stress response confers
      tolerance to a variety of stresses including hyperthermia, hyperoxia, hypoxia,
      and other perturbations, which alter protein synthesis. This tolerance phenomenon
      is also extremely important in the multicellular organism, resulting in not only
      thermal tolerance, but also resistance to stresses of the whole organism such as
      ischemia-reperfusion injury. Moreover, recent data indicates that these stress
      proteins have the ability to modulate the cellular immune response. Although the
      terms heat shock proteins (HSPs) and stress proteins are often used
      interchangeably, the term stress proteins includes the HSPs, the glucose
      regulated proteins (GRPs) and ubiquitin. The stress proteins may be grouped by
      molecular weight ranging from the large 110 kDa HSP110 to ubiquitin at 8 kDa.
      These proteins serve as cellular chaperones, participating in protein synthesis
      and transport through the various cellular compartments. Because these proteins
      have unique cellular localizations, the chaperone function of the stress proteins
      often involves a transfer of peptides between stress proteins as the peptide is
      moved between cellular compartments. For example, HSP70 is a cytosolic and
      nuclear chaperone, which is critical for the transfer of cellular peptides in the
      mitochondrion through a hand-off that involves mitochondrial HSP60 at the inner
      mitochondrial membrane. Similarly, cytosolic proteins are transferred from HSP70
      to gp96 as they move into the endoplasmic reticulum. The central role of the
      stress proteins in the transfer of peptides through the cell may be responsible
      for the recently recognized importance of the stress proteins in the modulation
      of the immune system [Feder, M.E., Hofmann, G.E., 1999. Heat-shock proteins,
      molecular chaperones, and the stress response: evolutionary and ecological
      physiology. Annu. Rev. Physiol. 61, 243-282.]. This importance in immune
      regulation is best addressed using Matzinger's model of the immune response - The
      Danger Theory of Immunity [Matzinger, P., Fuchs, E.J., 1996. Beyond self and non
      self: immunity is a conversation, not a war. J. NIH Res. 8, 35-39.]. Matzinger
      suggests that an immune system model based on the differentiation between "self
      and non-self" does not easily account for the changes that occur in the organism
      with growth and development. Why, for example does an organism not self-destruct
      when the immune system encounters the myriad of new peptides generated at
      puberty? Instead, she proposes a model of immune function based on the ability to
      detect and address dangers. This model states that the basic function of all
      cells of the organism is appropriately timed death "from natural causes". This
      type of cell death, or apoptosis, generates no stress signals. If, on the other
      hand, a cell is "murdered" by an infectious agent or dies an untimely death due
      to necrosis or ischemia, the cell undergoes a stress response with the liberation
      of stress protein-peptide complexes into the extracellular environment upon cell
      lysis. Not only do they serve as a "danger signal" to alert the immune system to
      the death of a cell under stress, but their role as protein carriers allows the
      immune effector cells to survey the peptides released by this stressed cell and
      to activate against new or unrecognized peptides carried by the stress protein.
      Matzinger bases the Danger Theory of Immunity on three "Laws of Lymphotics".
      These laws state that: (1) resting T lymphocytes require both antigen stimulation
      by an antigen-presenting cell (APC) and co-stimulation with a danger signal to
      become activated; (2) the co-stimulatory signal must be received through the APC;
      and (3) T cells receiving only antigen stimulation without the co-stimulatory
      signal undergo apoptosis. The Danger Theory gives a simple model for both
      tolerance and activation. (ABSTRACT TRUNCATED)

PMID- 10960672
TI  - Immune effects and therapeutic applications of CpG motifs in bacterial DNA.

PMID- 10960673
TI  - Immunotherapy approach to allergic disease.
AB  - The causal role of immunoglobulin E (IgE) in triggering the cascade of
      biochemical events leading to allergic disease is well established. Treatments
      that selectively inhibit IgE activity are a logical approach in managing the
      allergic response. One such strategy utilizes rhuMAb-E25, a recombinant humanized
      IgG(1) monoclonal anti-IgE antibody, which binds to IgE. This anti-IgE antibody
      binds at the same epitope site of IgE that binds to FcvarepsilonRI and is thus
      non-anaphylactogenic. By binding to IgE and removing it via immune complex
      formation, the pool of IgE available to interact with mast cells and basophils is
      thereby reduced and the allergic response is attenuated. The clinical safety and
      efficacy of rhuMAb-E25 demonstrated in phase II studies of allergic asthma will
      be outlined.

PMID- 10960674
TI  - Overview of immunotoxicology and current applications to respiratory diseases.
AB  - Immunotoxicology has been defined as the study of adverse effects on the immune
      system resulting directly from environmental, occupational, or therapeutic
      exposure to chemicals (including drugs), biological materials and, in certain
      instances, physiological factors, collectively referred to as agents. It
      encompasses immunosuppression, allergy, autoimmunity and inflammation.

PMID- 10960675
TI  - Models of respiratory immunotoxicology and host resistance.

PMID- 10960676
TI  - Air pollution and respiratory disease: extrapolating from animal models to human
      health effects.

PMID- 10960677
TI  - Diesel exhaust as a model xenobiotic in allergic inflammation.
AB  - We investigated the effects of diesel exhaust particulates on the human allergic
      response using in vivo human nasal challenges. Diesel particles and phenanthrene,
      one of their constituent polyaromatic hydrocarbons, were shown to enhance total
      allergic antibody (IgE) production, enhance allergen-specific IgE in the presence
      of allergen, and induce sensitization to a neoantigen.

PMID- 10960678
TI  - Immunologic mechanisms in granulomatous lung disease.

PMID- 10960679
TI  - Regulation of extracellular pH in the developing hippocampus.
AB  - The increased propensity of the immature brain to have seizures may be due, in
      part, to an inability to regulate the extracellular ionic environment. Here, we
      tested the regulation of extracellular pH in the developing hippocampus during
      and after intense neuronal activity induced by 20 Hz electrical stimulation in
      vivo. In CA1, stimulus trains to the CA3 region elicited an early alkaline shift
      associated with a later slow acid shift in all ages tested (2 weeks old, 3 weeks
      old and adult). In the dentate gyrus in adults, stimulation only elicited
      acidification. An initial alkalinization was only observed in the dentate gyrus
      in 2-week-old animals. The rate of recovery of the extracellular pH after
      termination of the stimulation was slower in the younger animals compared to
      adults in both CA1 and the dentate gyrus. The results indicate that the
      extracellular pH is regulated by mechanisms that undergo developmental changes
      that parallel the development of the dentate gyrus and development of the
      regulation of extracellular potassium.

PMID- 10960680
TI  - Thrombin action decreases acetylcholine receptor aggregate number and stability
      in cultured mouse myotubes.
AB  - Neurons develop and make very stable, long-term synaptic connections with other
      nerve cells and with muscle. Synaptic stability at the neuromuscular junction
      changes over development in that a proliferation of synaptic input are made to
      individual myotubes and synapses from all but one neuron are lost during
      development. In an established co-culture paradigm in which spinal motoneurons
      synaptically contact myotubes, thrombin and associated protease inhibitors have
      been shown to affect the loss of functional synaptic contacts [6]. Evidence has
      not been provided which clearly demonstrate whether protease/protease inhibitors
      affect either the pre- or postsynaptic terminal, or both. In an effort to
      determine whether these reagents directly affect postsynaptic receptors on
      myotubes, myotubes were cultured in the absence of neurons and the spontaneous
      presence and stability of aggregates of acetylcholine receptors (AChR) in control
      and thrombin-containing media were evaluated. In dishes fixed after treatment and
      in dishes in which individual aggregates were observed live, thrombin action
      appeared to increase loss of AChR aggregates over time. Hirudin, a specific
      inhibitor of the thrombin protease, diminished this loss. Neither reagent
      affected the overall incorporation or degradation of AChR; therefore, it appears
      these protease/protease inhibitors affect the state of AChR aggregation.

PMID- 10960681
TI  - Neurobehavioral damage to cholinergic systems caused by prenatal exposure to
      heroin or phenobarbital: cellular mechanisms and the reversal of deficits by
      neural grafts.
AB  - Despite the basic differences in their underlying biological targets, prenatal
      exposure to heroin or phenobarbital produces similar syndromes of neurobehavioral
      deficits, involving defects in septohippocampal cholinergic innervation-related
      behaviors. At the cellular level, these deficits are associated with cholinergic
      hyperactivity, characterized by increased concentrations of muscarinic receptors
      and enhanced second messenger activity linked to the receptors. In the present
      study, we determined whether the cellular changes are mechanistically linked to
      altered behavior, using two different approaches: neural grafting and
      correlations between behavior and biochemistry within the same individual
      animals. Mice were exposed transplacentally to phenobarbital or heroin on
      gestation days 9-18 and, as adults, received fetal cholinergic grafts or were
      sham-operated. Prenatal drug exposure resulted in deficits in behavioral
      performance tested in the eight-arm radial maze, accompanied by increases in
      hippocampal M(1)-muscarinic receptor expression and muscarinic receptor-mediated
      IP formation. Neural grafting reversed both the behavioral deficits and the
      muscarinic hyperactivity. In the drug-exposed offspring, there was a significant
      correlation between maze performance and carbachol-induced inositol phosphate
      (IP) formation. These studies indicate that deficits of cholinergic function
      underlie the neurobehavioral deficits seen in the hippocampus of animals exposed
      prenatally to heroin or phenobarbital, and consequently that the observed
      cholinergic hyperactivity is an unsuccessful attempt to compensate for the loss
      of cholinergic function. The fact that the damage can be reversed by neural
      grafting opens up novel approaches to the restoration of brain function after
      prenatal insults.

PMID- 10960683
TI  - Neonatal estrogen blockade prevents normal callosal responsiveness to estradiol
      in adulthood.
AB  - The rat corpus callosum (CC) is larger in males than females, and is responsive
      to hormone manipulations during development. We previously demonstrated that P25
      ovariectomy (Ovx) enlarged (defeminized) adult CC, while P70 ovary transfer (OvT)
      counteracted this enlarging effect, resulting in smaller (feminized) CC. Since
      OvT females were not Ovx'd until P25, they received some neonatal estrogen (E)
      exposure. Behavioral data suggest that adult responsiveness to ovarian hormones
      depends upon prior organization by neonatal E. It has not been determined whether
      a similar phenomenon occurs for the feminization of brain morphology. The current
      experiment examined whether our previous finding of adult CC responsiveness to
      ovarian hormones depended upon neonatal E exposure. We investigated this by
      assessing the effects of P70 ovarian hormone replacement (via ovary transfer or E
      pellet) in females that received either (1) normal ovarian hormone exposure until
      P25 Ovx, or (2) the E receptor blocker tamoxifen from birth to P25 Ovx. Females
      receiving normal neonatal hormone exposure responded to P70 E in the female
      typical manner: E reduced CC size. In contrast, females receiving neonatal E
      blockade responded to adult E in the opposite manner: E increased CC size. As far
      as we are aware, this is the first report suggesting that neonatal E exposure
      organizes the female brain so that it responds normally to the organizing actions
      of E when later exposure occurs. These findings further challenge the traditional
      model of female brain development, which asserts that normal female brain
      organization occurs by default, in the absence of gonadal hormone exposure.

PMID- 10960682
TI  - Detection of caspase-9 activation in the cell death of the Bcl-x-deficient mouse
      embryo nervous system by cleavage sites-directed antisera.
AB  - Caspases, which play crucial roles during apoptosis, are activated from their
      inactive proforms in a sequential cascade of cleavage by other members of the
      caspase family. Caspase-9 is autoprocessed by the Apaf-1/cytochrome c pathway and
      acts at an early point in this cascade, whereas Bcl-xL, an antiapoptotic member
      of the Bcl-2 family, prevents activation of caspases in vitro. Little is known,
      however, about the relation between caspase-9 and Bcl-xL during development of
      the mammalian nervous system. We used antisera against two cleavage sites in
      mouse caspase-9 that recognize only the activated form of mouse caspase-9, and we
      examined immunohistochemically the activation of mouse caspase-9 in the nervous
      system of Bcl-x-deficient mouse embryos. Mouse caspase-9 is processed at both
      D(353) and D(368), but it is processed preferentially at D(368) during apoptosis
      of cultured cells induced by various stimuli and in the nervous system of Bcl-x
      deficient mouse embryos. We show that Bcl-xL protects against caspase-9- and/or
      caspase-3-dependent apoptosis in the caudal portion of the ventral hindbrain,
      anterior horn cells, and dorsal root ganglia neurons of the normal mouse embryos
      and against caspase-9/caspase-3-independent apoptosis in the dorsal region of the
      nervous system including the dorsal spinal cord. Furthermore, we demonstrate that
      Bcl-xL blocks cytochrome c release from mitochondria, causing activation of
      caspase-9 in anterior horn cells and dorsal root ganglia neurons in mouse embryos
      at embryonic day 11.5.

PMID- 10960684
TI  - Sex differences in the response of postnatal rat lumbar lamina X neurons to
      exogenously applied galanin recorded in vitro.
AB  - Intracellular recording techniques were used in a horizontal slice preparation of
      postnatal rat lumbar spinal cord to compare the responses of male and female
      lamina X neurons to exogenously applied galanin. Although there was no
      significant sex difference in the resting membrane potential or input resistance
      of neurons, superfusion of galanin 1-16 (1 microM) produced a membrane
      hyperpolarization that averaged -5.3 mV in males and only -2.0 mV in females. The
      galanin-induced membrane hyperpolarization of lamina X neurons was accompanied by
      an inconsistent and varied change in input resistance. No depolarizing effect of
      galanin was detected in either sex. Galanin did not significantly alter the spike
      shape, amplitude, after hyperpolarization or locally evoked synaptic responses.
      The more than 2.5 fold significant sex difference in response to galanin occurred
      at a developmental timepoint at which lamina X expressed a comparably higher
      amount of galanin-like immunoreactivity in males compared to females. These
      results provide the first indication of a sex difference in the response of
      lamina X neurons to any neuropeptide. Given the antinociceptive role of galanin
      in the spinal cord, these results raise the possibility for the presence of
      distinct physiological and anatomical substrates for sex-dependent differences in
      nociceptive processing in lamina X of the lumbosacral spinal cord.

PMID- 10960685
TI  - The weaver gene has no effect on the generation patterns of mesencephalic
      dopaminergic neurons.
AB  - To determine if the weaver gene has action on late-generated neurons in midbrain
      areas on postnatal day (P) 8 [(3)H] thymidine autoradiography and tyrosine
      hydroxylase immunohistochemistry were combined in the same tissue section in
      homozygous weaver mice and normal controls. The experimental animals were the
      offspring of pregnant dams injected with [3H] thymidine on embryonic days (E)11
      12, E12-13, E13-14 and E14-15. Both the span of neurogenesis and the neurogenetic
      timetables of dopaminergic neurons were similar between wild-type and homozygous
      weavers in all midbrain areas analyzed. No loss of late-generated dopaminergic
      neurons was observed. The cytoarchitecture of the midbrain dopaminergic cell
      groups were also the same in both experimental groups indicating that cell
      migration, settling, and cytodifferentiation proceeds normally in spite of the
      presence of the weaver gene.

PMID- 10960687
TI  - Developmental expression of opioid-binding cell adhesion molecule (OBCAM) in rat
      brain.
AB  - Opioid-binding cell adhesion molecule (OBCAM), a neuron-specific protein,
      consists of three immunoglobulin (Ig)-like domains anchored to the membrane
      through a glycosylphosphatidylinositol (GPI)-tail. OBCAM has been presumed to
      play a role as a cell adhesion/recognition molecule, but its function has not
      been fully elucidated. We investigated the developmental expression of OBCAM in
      rat brain by using a monoclonal anti-OBCAM peptide antibody (OBC53). OBCAM was
      clearly detectable on embryonic day 16 (E16) as assessed by immunoblotting. The
      expression level increased by the second postnatal week and was maintained at a
      constant level until week 17. During the early developmental period OBCAM was
      found to be expressed on postmitotic neurons and to be strongly expressed in at
      the fiber tracts containing expanding axons, in contrast to the adult brain, in
      which OBCAM is principally expressed in the gray matter. These findings suggest
      that the function of OBCAM involves axonal outgrowth.

PMID- 10960686
TI  - The weaver gene continues to target late-generated dopaminergic neurons in
      midbrain areas at P90.
AB  - To determine if lethal action of the weaver gene is more intense in late
      generated dopaminergic neurons in midbrain areas on postnatal day (P) 90 [3H]
      thymidine autoradiography and tyrosine hydroxylase immunohistochemistry were
      combined in the same tissue section in homozygous weaver mice and normal
      controls. The experimental animals were the offspring of pregnant dams injected
      with [3H] thymidine on embryonic days (E) 11-12, E12-13, E13-14 and E14-15.
      Neurogenetic timetables of dopaminergic neurons were different between wild type
      and homozygous weavers in all midbrain areas analyzed. A substantial number of
      late-generated neurons in the substantia nigra pars compacta and in the ventral
      tegmental area are missing at P90, in these dopaminergic areas the loss is
      greater than at P20 indicating that neuronal loss is progressive. The greatest
      loss is in the substantia nigra pars compacta, confirming the report of Bayer et
      al. [Exp. Brain Res. 105 (1995) 200] at P20, while in the retrorubral field and
      the interfascicular nucleus late-generated neuron loss was less severe. These
      results furnish more evidence that dopaminergic neuron loss in homozygous weaver
      midbrain is a phenomenon linked to development.

PMID- 10960689
TI  - Hearing defects in children born of mothers suffering from rubella in the first
      trimester of pregnancy.
AB  - The investigations concerned women that had suffered from symptomatic rubella in
      the first trimester of pregnancy. The presence of immunoglobulin G and
      immunoglobulin M antibodies in mothers and their children was detected, and the
      hearing organ was examined. In early childhood (up to 3 years of age), hearing
      loss was confirmed in 50% of the children born of mothers with rubella.

PMID- 10960688
TI  - Abnormal chloride and potassium conductances in cultured embryonic tongue muscle
      from trisomy 16 mouse.
AB  - Trisomy 16 (Ts16) mouse is considered an animal model of Down syndrome (human
      trisomy 21). Whole-cell patch-clamp was used to evaluate potassium and chloride
      currents of cultured tongue muscle cells from fetal Ts16 and diploid mice. No
      difference was found in membrane capacitance between the two groups. K(+) and Cl(
      ) currents were pharmacologically isolated. K(+) conductance was reduced by 31%
      in Ts16 cells (373 pS/pF) compared with diploid cells (539 pS/pF). Cl(-)
      conductance was 51% larger in Ts16 cells (103 pS/pF) compared with diploid cells
      (68 pS/pF). However kinetics for K(+) and Cl(-) currents did not differ between
      the cell types. An increase in Cl(-) conductance and a decrease in K(+)
      conductance in Ts16 muscle cells, if present in muscle of Down syndrome subjects,
      might account for the observed hypotonia in these subjects.

PMID- 10960690
TI  - Turnover of Haemophilus influenzae isolates in otitis-prone children.
AB  - INTRODUCTION: Previous studies have suggested a direct relationship between the
      nasopharyngeal carriage of potential middle ear pathogens and the development of
      middle ear disease. It has been shown that otitis-prone (OP) children tend to be
      colonized more often than non-OP children. To study the turnover of nontypeable
      Haemophilus influenzae (NTHI) in the nasopharynx of OP children, arbitrarily
      primed PCR was applied to NTHI strains isolated nasopharyngeal swabs collected
      prospectively during a 2-year study period from 35 OP children under 4 years of
      age at fixed intervals. METHODOLOGY/MATERIALS: In 20 patients, H. influenzae
      could be isolated from different sites (left and/or right ear and/or nasopharynx)
      or at different occasions during follow-up. Forty-eight H. influenzae isolates of
      different sites (left and/or right ear and/or nasopharynx) of the same patient as
      well as from siblings were typed using arbitrarily primed PCR with primer ERIC2
      and RAPD Ready-to-Go beads (Pharmacia Biotech, Uppsala, Sweden). RESULTS: Typing
      with arbitrarily primed PCR enabled to differentiate 29 genotypes among the 48 H.
      influenzae isolates. Sixteen of these fingerprints were observed only once.
      Thirteen of these fingerprints appeared on two or more occasions. In the three
      pairs of siblings the same strain was identified at one moment. Genetically
      identical NTHI strains from unrelated individuals were never identified. In 11 of
      14 cases for which isolates were obtained simultaneously from different sites
      (throat and/or left ear and/or right ear) or from three pairs of siblings,
      identical fingerprints were observed. In nine cases whereby isolation was
      separated by a period of more than 4 weeks (maximum 28 weeks) the fingerprints of
      the isolates were different from the original isolate. CONCLUSION: Typing with
      arbitrarily primed PCR indicated substantial genetic diversity among the H.
      influenzae isolates studied, since for a total of 48 isolates of 20 different
      patients, 29 different genotypes were observed. Since simultaneous isolation for
      different sampling sites (ear or nasopharynx) as well as for both of siblings,
      resulted mostly in identical fingerprints, and since sampling of the same site of
      the same patient, separated by an interval of more than 1 month, almost always
      resulted in different genotypes, one could conclude that both cross colonization
      (between sampling sites within the same patient and between siblings) and
      turnover are high. The relation between acquisition and development of disease
      needs further attention.

PMID- 10960691
TI  - On the physics of the infant feeding bottle and middle ear sequela: ear disease
      in infants can be associated with bottle feeding.
AB  - BACKGROUND: When using conventional feeding bottles, negative pressure is
      generated in the oral cavity, as well as, in the bottle when fluid is removed by
      sucking. The negative pressure inside the bottle causes the infant to suck
      excessively and the intraoral negative pressure may subsequently be transmitted
      to the middle ear via the eustachian tube. METHODS: in seven infants,
      simultaneous pressure recordings were performed in the feeding vessel and the
      middle ear using three types of feeding bottles. RESULTS: with conventional non
      ventilated and under-ventilated bottles a negative pressure formed while the
      infant sucked and negative intratympanic pressure was frequently generated.
      CONCLUSIONS: it is suggested that this sequence of events may lead to secretory
      otitis and it's accompanying consequences. In contrast, a fully ventilated bottle
      showed positive pressure throughout the feeding procedure, which is similar to
      normal breast-feeding, and negative pressure changes were not recorded in the
      middle ear.

PMID- 10960692
TI  - Doppler echocardiography in adenotonsillar hypertrophy.
AB  - OBJECTIVE: Adenotonsillar hypertrophy causing upper airway obstruction may lead
      to the pulmonary hypertension and cor pulmonale. This study aimed to clarify the
      diagnostic methods of this complication, besides polysomnography, to find another
      objective criterion for surgical intervention and to demonstrate the curative
      effect of adenotonsillectomy on this complication using this objective criterion.
      METHODS: We studied the outcomes of 17 children with pulmonary hypertension
      secondary to the adenotonsillar hypertrophy. Pulmonary arterial pressure
      measurement was performed noninvasively by Doppler echocardiography. RESULTS:
      Mean preoperative pulmonary arterial pressure was 29.12+/-4.41 mmHg and decreased
      dramatically after relief of upper airway obstruction by adenoidectomy and/or
      tonsillectomy to the normal level of 12.06+/-3.09 mmHg. These results were
      analyzed by equal variances t-test and found very significant (P<0.01). Regarding
      the symptoms of upper respiratory obstruction, symptom scores of these children
      decreased very significantly and were analyzed by equal variances t-test (P<0.
      01) in the postoperative period. For all the symptoms individually (snoring,
      mouth-breathing during sleep and daytime, hyponasal voice, restless sleeping,
      daytime somnolence, enuresis nocturna), comparing percentages of preoperative and
      postoperative symptoms by unequal variances t-test, we obtained very significant
      decrease (P<0.01). CONCLUSIONS: This study illustrates that Doppler
      echocardiography is a safe, practical and noninvasive-method in diagnosing
      cardiovascular disturbances--one of the complications of adenotonsillar
      hypertrophy and especially for measuring the pulmonary arterial pressure. All the
      symptoms and disorders due to the adenotonsillar hypertrophy may be reversible by
      performing early adeno- and/or tonsillectomy.

PMID- 10960693
TI  - Clinical presentation as a guide to the identification of GERD in children.
AB  - OBJECTIVE: to determine if there is a correlation between common otolaryngologic
      symptoms and presence of gastroesophageal reflux disease (GERD) in children.
      METHODS: charts of 295 children presenting with suspicion of GERD were reviewed
      for presenting symptoms including: (1) airway symptoms: stertor, stridor,
      frequent cough, recurrent croup, wheezing, nasal congestion, obstructive apnea,
      blue spells, hoarseness, throat clearing; (2) feeding symptoms: wet burps, globus
      sensation, frequent emesis, dysphagia, choking/gagging, sore throat, halitosis,
      food refusal, stomach aches, arching, drooling, chest pain, irritability, and
      failure to thrive. At least one positive test of barium esophagram, gastric
      scintiscan, pH probe or esophageal biopsy resulted in inclusion in the GERD
      positive group. RESULTS: 214 children had GERD diagnosed while 81 had no positive
      tests for GERD. Between the GERD positive and GERD negative groups, the
      significantly different symptoms were stertor (P=0.040), cyanotic spells
      (P=0.043), frequent emesis (P=0.007), failure to thrive (P=0.006), and
      choking/gagging (P=0.044). Three pooled variables were created: airway flow
      (stertor, stridor, cyanotic spells), airway irritation (frequent cough, recurrent
      croup, throat clearing), and feeding (dysphagia, failure to thrive, frequent
      emesis). GERD patients who were 2 years or less were compared to those older than
      2 years and all three of these pooled variables were significantly different
      between these groups (P<0. 001). CONCLUSION: children who present with a certain
      constellation of airway or feeding symptoms are more likely to have a positive
      GERD test. Children 2 years old or less are more likely to present with airway
      symptoms or feeding difficulties while children older than 2 years are more
      likely to present with airway irritation.

PMID- 10960694
TI  - Mandibulofacial dysostosis: CT evaluation of the temporal bones for surgical risk
      assessment in patients of bilateral aural atresia.
AB  - We present the results of detailed CT investigation of nine patients with
      mandibulofacial dysostosis (MFD). We also graded the severity of microtia
      according to Marx's classification system. The results revealed a positive
      correlation between the severity of microtia and the severity of deformity of the
      external auditory canal, and attic formation. In 13 ears, the stapes was not
      adequately visualized to allow any comment on its form. The angle of the first
      genu of the facial nerve ranged from 55.0 to 123.6 degrees (mean +/-S.D.; 99.5 +/
      18.5 degrees ), indicating that this angle is more obtuse in MFD patients than in
      normal subjects. The eustachian tube and tympanic sinus were present in all the
      ears examined. None of the patients had mastoid pneumatization. In four ears, the
      lateral semicircular canal was dysplastic. Eleven ears of six patients scored
      less than 5 in the grading system developed by Jahrsdoerfer for assessment of the
      suitability for atresia surgery. These findings indicate that most patients with
      mandibulofacial dysostosis are poor surgical candidates.

PMID- 10960695
TI  - Treacher Collins syndrome with acute airway obstruction.
AB  - Treacher Collins syndrome presents with cranio-facial deformities of variable
      expressions and severity, but rarely is it associated with acute airway
      obstruction of such severity that it necessitates surgical intervention. The
      authors describe their experience with such a neonate, who presented with acute
      airway obstruction successfully managed with a tracheostomy. The relevant English
      literature is reviewed.

PMID- 10960696
TI  - An atypical presentation of Kawasaki disease resembling a retropharyngeal
      abscess.
AB  - Kawasaki disease is an acute systemic inflammatory disease, which occurs in
      children less than 10 years of age. The etiology of the disorder is unknown.
      Diagnosis is based upon clinician's recognition of a symptom pattern that
      includes high fevers, oral cavity changes, polymorphous rash, conjunctival
      injection, and cervical adenopathy. Most feared are the cardiac manifestations of
      Kawasaki syndrome, which result in an overall mortality rate of 2% in patients.
      Because of the common presenting symptoms, the otolaryngologist often plays a
      central role in early diagnosis of the disorder. The following case report
      describes a patient with Kawasaki disease whose initial presentation mimicked a
      retropharyngeal abscess. A literature review details the common and atypical
      early signs and symptoms of Kawasaki disease.

PMID- 10960697
TI  - The syndrome of frontonasal dysplasia, spastic paraplegia, mental retardation and
      blindness: a case report with CT scan findings and review of literature.
AB  - Frontonasal dysplasia is defined as hypertelorism, telecanthus and broad bridge
      of the nose with absent or bifid tip of the nose. The clinical, the CT scan and
      the operative findings of a case of frontonasal dysplasia with spastic
      paraplegia, mental retardation, blindness, and cleft lip and cleft palate are
      discussed. The contemporary literatures on this rare congenital anomaly are also
      reviewed.

PMID- 10960698
TI  - Rapid resolution of fetal goiter associated with maternal Grave's disease: a case
      report.
AB  - The incidence of abnormal fetal thyroid function with maternal Grave's disease is
      about 2-12%. The development of larger fetal goiters can complicate labor and
      precipitate life-threatening airway obstruction at delivery. A case is presented
      of a large stable goiter confirmed by sonography, which unexpectedly resolved by
      the time of parturition. A 3 x 6 cm fetal goiter was detected at 34 weeks
      gestation in a mother treated with propylthiouracil for Grave's disease. A repeat
      sonogram at 36 weeks showed no change in goiter size. Umbilical blood sampling
      showed the fetus to be markedly hyperthyroid. Planned Cesarean section took place
      11 days after the final sonogram. A multi-disciplinary operative team was present
      including the Otolaryngology service with equipment for emergency intubation,
      bronchoscopy and tracheotomy. Upon delivery, the infant had no evidence of goiter
      and no airway compromise. Fetal goiter is a rare entity, and recent advances in
      the field of maternal-fetal medicine have enabled intra-uterine diagnosis and
      treatment of such conditions. A review of published case reports demonstrates two
      trends in treated fetuses: preterm progressive resolution of the goiter, or
      delivery with gross evidence of goiter. This reported case is unique, as a
      persistent goiter resolved completely in less than 2 weeks. Otolaryngologic
      response to and management of potential congenital airway compromise is
      discussed.

PMID- 10960699
TI  - Comparison of a point mutation assay with a line probe assay for the detection of
      the major mutations in the HIV-1 reverse transcriptase gene associated with
      reduced susceptibility to nucleoside analogues.
AB  - This study compares the performance of a line probe assay (LiPA) for the
      detection of the major mutations associated with reduced sensitivity to
      nucleoside analogues with a well characterised point mutation assay (PMA). Plasma
      samples obtained from patients in a trial of four reverse transcriptase
      inhibitors (MRC Quattro Trial) were tested by both LiPA and PMA at baseline, 32nd
      and 64th weeks for the presence of drug resistance associated mutations in the
      reverse transcriptase (RT) gene. HIV-1 RNA was extracted from plasma by the Boom
      method and amplified by RT-PCR prior to being tested by LiPA or PMA. Assay
      discrepancies were further investigated by sequencing of the RT gene. Of 275
      samples available from 98 trial subjects, 246 samples were successfully amplified
      by PCR and analysed by LiPA and PMA for six mutations. Of the 1476 individual
      codons analysed, LiPA successfully assayed 1444 (97.8%) and PMA gave a result
      with 1418 (96.1%). LiPA failed to give a result for 32 codons from 22 samples and
      PMA failed with 58 codons from 38 samples. Gross differences between the two
      assays, in which one scored a codon as wild-type only and the other as mutant
      only or vice versa, occurred at 28 codons analysed (1.9%) representing 26 samples
      from 20 subjects. Sequencing of 22 of the 26 samples confirmed the LiPA result in
      nine cases, the PMA result in 11 and detected a novel variant at codon 215 in
      four cases. The PMA and LiPA approach to the detection of the major mutations
      that are genotypically associated with reduced sensitivity to nucleoside
      analogues can correctly detect mutations in 97% of the cases.

PMID- 10960700
TI  - Comparison of five different polymerase chain reaction methods for detection of
      human papillomavirus in cervical cell specimens.
AB  - The polymerase chain reaction (PCR) methods enable the detection of large number
      of human papillomavirus (HPV) genotypes that infect the anogenital tract. In this
      study, two groups of cervical scrapes with abnormal cytomorphology were analysed.
      The first group was tested with three sets of consensus primers located within
      the L1 region of HPV genome, MY09/MY11 (i.e. MY), L1C1/L1C2-1/L1C2-2 (i.e. LC)
      and pI-1/pI-2 (i.e. pI) primer sets, while the second group of samples, which
      were all negative with the MY primers, was tested further with the LC primers, as
      well as with the GP5/GP6 (i.e. GP) primers. The GP primers were used in the
      nested PCR following amplification with the MY primers (i.e. MY/GP nested PCR).
      Samples from both groups were also tested with type-specific primers for HPV
      types 6/11, 16, 18, 31 and 33. In the first study group (N=164) there were 76.2%
      positive results obtained with at least one set of consensus primers. There were
      62.2, 39, 62.2 and 59.1% positive results obtained with the MY, the pI, the LC
      and the HPV type-specific primer sets, respectively. The best results were
      obtained when both the MY and the LC primer sets were used, because in
      combination they detected 75% positive samples compared to 62.2% when used alone.
      There were 2. 4% samples negative with all consensus primers, but positive with
      one of the HPV type-specific primers, which increased the overall positivity rate
      to 78.6%. In the second study group (N=250) there were 8.4, 38.8 and 4% samples
      positive with the LC primers, the nested MY/GP and the HPV type-specific primer
      sets, respectively. Thus, the use of the MY/GP nested PCR increased significantly
      the positivity rate of HPV DNA detection and should be used for samples with a
      low copy number of HPV DNA. In conclusion, the following diagnostic protocol
      would be appropriate for detection of cancer-related HPVs: preselection of
      samples with the MY and the LC primers, additional amplification of the MY- and
      the LC-negative samples with the MY/GP nested PCR and HPV typing of consensus PCR
      positive samples with the HPV type-specific primers.

PMID- 10960701
TI  - Development of probes for typing African horsesickness virus isolates using a
      complete set of cloned VP2-genes.
AB  - A set of cloned full-length VP2-genes from the reference strain of each of the
      nine serotypes of African horsesickness virus (AHSV) was used to develop probes
      for typing AHSV isolates. The VP2-gene probes hybridised serotype-specific to
      purified viral dsRNA from its corresponding serotype. No cross-hybridisation was
      observed between the different AHSV serotypes or with RNA from equine
      encephalosis virus or bluetongue virus (BTV) which are related viruses within the
      genus Orbivirus that co-circulate with AHSV in South Africa. The probes were able
      to detect AHSV isolates from recent field cases of AHS in South Africa, despite
      being derived from historical reference strains. With regard to sensitivity and
      time considerations: radioactive 32P-labelling resulted in a marginal increase in
      sensitivity over digoxigenin-labelled probes. By infecting cell cultures at
      different multiplicities of infection (m.o.i.) and harvesting at various times
      post infection, it was established that AHSV RNA could be detected 16 h post
      infection (p.i.) at a m.o.i. of 1.00 pfu per cell and 48 h p.i. at a m.o.i. of
      0.01 pfu per cell. Typing of AHSV isolates by means of VP2-gene probe
      hybridisation can be completed in 4 days, which is less than half the time
      required for conventional isolation and serotyping. This report on the use of a
      complete set of cloned AHSV VP2-gene probes is the first demonstration of typing
      for a whole specie (serogroup) in a genus of the family Reoviridae.

PMID- 10960702
TI  - Peroral infection of nuclear polyhedrosis virus budded particles in the host,
      Bombyx mori l., enabled by an optical brightener, Tinopal UNPA-GX.
AB  - Perorally inoculated budded particles of a nuclear polyhedrosis virus was used to
      infect Bombyx mori (BmNPV) (Lepidoptera; Bombycidae), aided by an optical
      brightener, Tinopal UNPA-GX (Tinopal). BmNPV budded particles not occluded in the
      occlusion body do not infect successfully the host, B. mori, when administered
      perorally. It was found that feeding the host Tinopal enabled perorally delivered
      BmNPV budded particles to infect the host. B. mori larvae ingesting BmNPV budded
      particles (1.3 x 10(6) TCID(50) units per larva) after they consumed an
      artificial diet containing 0. 3% Tinopal died of the viral infection. Peroral
      administration of these particles to host larvae with 1% Tinopal also resulted in
      virus infection. Tinopal is a candidate for viral activity enhancing agent
      promoting viral insecticide infection in hosts. The results suggest that B. mori
      BmNPV budded particles are convenient for detecting viral infection enhancement
      activity of a chemical of interest. Since recombinant baculovirus vectors are
      constructed by replacing the polyhedrin gene with the foreign gene of interest,
      they do not produce occlusion bodies, i.e. polyhedra. Budded particles of a
      baculovirus vector not occluded in polyhedra cannot infect their hosts when
      administered perorally. The peroral inoculation of BmNPV budded particles by
      Tinopal leads to industrial pharmaceutics production using a baculovirus vector
      for a huge number of insect hosts, i.e. an 'insect factory'.

PMID- 10960703
TI  - RT-PCR using redundant primers to detect the three viruses associated with carrot
      motley dwarf disease.
AB  - A method was developed for detecting and distinguishing the viruses associated
      with carrot motley dwarf (CMD) disease, i.e. Carrot mottle umbravirus (CMoV),
      Carrot red leaf virus (CRLV) and the virus known as carrot red leaf virus
      associated RNA (CRLVaRNA). Redundant primers were made that targeted the RNA
      dependent RNA polymerase (RdRp) gene in all available sequences of umbraviruses
      and in a subset of polerovirus genomes, and specific and redundant primers were
      made to target the same gene in CRLVaRNA. By using these primers in RT-PCR
      reactions, cDNAs were amplified from total RNA isolated from Belgian parsley with
      CMD disease. The cDNAs were sequenced and an analysis of this data showed that
      the plants contained all three viruses. RT-PCR assays were optimized for the
      simultaneous detection of the three viruses in infected parsley and chervil
      plants and in individual viruliferous aphids. This is the first report of a
      natural infection of CRLVaRNA in a plant other than carrot and the first report
      of this virus outside the USA. The study also confirmed that the umbravirus in
      parsley with CMD disease is CMoV, and that this virus is distinct from carrot
      mottle mimic umbravirus (CMoMV), which is also associated with CMD, but
      apparently not in Europe.

PMID- 10960704
TI  - Detection of phages infecting Bacteroides fragilis HSP40 using a specific DNA
      probe.
AB  - Nine bacteriophage isolates of Bacteroides fragilis, obtained from urban sewage
      and pig faeces samples using four different host strains (HSP40, RYC4023, RYC2056
      and RYC3318), were compared on the basis of morphology, host range, DNA
      restriction patterns, DNA hybridisation and protein composition. All the phages
      are siphovirus and, as judged from cleavage by restriction endonucleases, their
      genome is composed of double-stranded DNA of similar size ( approximately 51-kb).
      Host range analysis differentiated two types of phages: (1) phages that clearly
      infect B. fragilis strains HSP40 (B40-2, B23-1, B23-2, B23-3 and B23-4, of which
      B40-8 is the phage type); and (2) the group of bacteriophages that were not
      infectious for HSP40 (B56-1, B56-2 and B18-1). Similarity in DNA restriction
      patterns and protein characteristics was found in the HSP40 infectious phages.
      Anti-B40-8 serum recognised only the proteins of the phages of this type.
      Although all phages showed similar major protein sizes, minor specific bands were
      detected. Bacteriophages B56-1, B56-2 and B18-1 showed heterogeneity in their DNA
      restriction profiles although some degree of DNA-DNA homology between all genomes
      was observed. Southern blot analysis with phage B40-8 DNA based probes identified
      a 1.5-kb DNA region homologous for all HSP40 phage isolates, but absent in the
      genome of the other phage isolates that did not infect this bacterial strain. The
      homologous region was used as a specific probe to specifically detect B. fragilis
      HSP40 phages.

PMID- 10960705
TI  - Rapid concentration and detection of hepatitis A virus from lettuce and
      strawberries.
AB  - Immunomagnetic beads-PCR (IM-PCR), positively-charged virosorb filters (F), or a
      combination of both methods (F-IM-PCR) were used to capture, concentrate and
      rapidly detect hepatitis A virus (HAV) in samples of lettuce and strawberries
      experimentally contaminated. Direct reverse transcriptase-polymerase chain
      reaction (RT-PCR) amplification of the collected HAV-beads complex showed a
      detection limit of 0.5 plaque forming units (PFU) of the virus present in 1-ml of
      wash solution from the produce, which was several hundred-fold more sensitive
      than that demonstrated by RT-PCR. In separate trials, virus-containing wash
      solutions from the produce were passed through the filters and the captured virus
      was eluted with 10 ml volumes of 1% beef extract. Of the 62% filter-captured HAV,
      an average of 34.8% was eluted by the 1% beef extract. PCR amplification of 2
      microl from this eluate failed to produce a clear positive band signal. As little
      as 10 PFU, present on each piece of the lettuce or strawberry, was detectable by
      the F-IM-PCR, which was almost 20 times less sensitive than the detection limit
      of 0.5 PFU by the IM-PCR. However, considering the large volumes (< or =50 ml)
      used in the F-IM-PCR, the sensitivity of detection could be much greater than
      that of the IM-PCR, which was restricted to < or =20 ml volumes. These data
      indicate that the F-IM-PCR method provides the potential for a greater
      sensitivity of detection than the IM-PCR, since low levels of virus could be
      detected from large volumes of sample than possible by the IM-PCR method.
      Although positively-charged filters captured a greater amount of virus than both
      the IM-PCR and F-IM-PCR methods, direct PCR amplification from beef extract
      eluates was not successful in detecting HAV from produce.

PMID- 10960706
TI  - A sensitive method for the detection of foot and mouth disease virus by in situ
      hybridisation using biotin-labelled oligodeoxynucleotides and tyramide signal
      amplification.
AB  - An in situ hybridisation technique, based on oligodeoxynucleotide probes and
      tyramide signal amplification, is described for the detection of foot and mouth
      disease virus RNA in infected cells. Biotinylated oligodeoxynucleotide probes,
      with and without tyramide signal amplification, were compared. The tyramide
      signal amplification detection enhances by at least 100-fold the sensitivity of
      in situ hybridisation.

PMID- 10960707
TI  - RT-PCR, nucleotide, amino acid and phylogenetic analyses of enterovirus type 71
      strains from Asia.
AB  - A specific and sensitive method based on RT-PCR was developed to detect
      enterovirus 71 (EV71) from patients with hand, foot and mouth disease,
      myocarditis, aseptic meningitis and acute flaccid paralysis. RT-PCR primers from
      conserved parts of the VP1 capsid gene were designed on the basis of good
      correlation with sequences of EV71 strains. These primers successfully amplified
      44 strains of EV71 including 34 strains isolated from Singapore in 1997 and 1998,
      eight strains from Malaysia isolated in 1997 and 1998, one Japanese strain and
      the neurovirulent strain EV71/7423/MS/87. RT-PCR of 30 strains of other
      enteroviruses including coxsackievirus A and B, and echoviruses failed to give
      any positive amplicons. Hence, RT-PCR with these primers showed 100% correlation
      with serotyping. Direct sequencing of the RT-PCR products of 20 EV71 strains
      revealed a distinct cluster with two major subgroups, thus enabling genetic
      typing of the viruses. The genetic heterogeneity of these strains culminated in
      amino acid substitutions within the VP1, VP2 and VP3 regions. The sequencing of a
      2.9 kb fragment comprising the capsid region and the major part of 5' UTR of two
      Singapore strains revealed that they belonged to a group distinct from the
      prototype EV71/BrCr strain and the EV71/7423/MS/87 strain. The dendrogram
      generated from 341 bp fragments within the VP1 region revealed that the strains
      of Singapore, Malaysia and Taiwan belong to two entirely different EV71
      genogroups, distinct from the three genogroups identified in another recent
      study.

PMID- 10960708
TI  - Detection of porcine enteroviruses by nRT-PCR: differentiation of CPE groups I
      III with specific primer sets.
AB  - Porcine enteroviruses (PEV) comprising at least 13 serotypes grouped into three
      species are described as causative agents of neurological disorders, fertility
      disorders, and dermal lesions of swine. Despite their well-documented acid
      stability, enteric infection route, and similarity of clinical symptoms, most of
      the porcine enterovirus (PEV) serotypes are set apart from the genus Enterovirus
      of the Picornaviridae. Hence, PCR procedures used commonly to detect
      enteroviruses are not applicable to epizootic relevant PEV serotypes. A nested RT
      PCR protocol is described now suited to detect all known porcine enterovirus
      serotypes using three sets of primer pairs. These primer pairs were designed to
      amplify either highly conserved sequences of the 5'-nontranslated region (5'-NTR)
      or the polymerase gene region of the relevant virus species. All 13 acknowledged
      serotypes of three PEV species and several field isolates of clinical specimens
      were detectable. The specificity of the PCR procedure is supported by the
      observation that RT-PCR-positive field isolates coincide with serological PEV
      classification. PEV PCR is more rapid and less laborious than the time-consuming
      virus isolation by tissue culture techniques over several passages and
      serotyping. Because other viruses such as classical swine fever virus,
      pseudorabies virus, porcine parvovirus, swine vesicular disease virus, and foot
      and-mouth disease virus may cause diseases with similar clinical symptoms, PCR
      detection of all PEVs closes a diagnostic gap and offers the opportunity to use
      comprehensive PCR procedures for the diagnosis of all relevant viruses causing
      such symptoms.

PMID- 10960709
TI  - A rapid plate assay for the screening of inhibitors against herpesvirus DNA
      polymerases and processivity factors.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly identified human
      pathogen with tumorigenic potential. The DNA polymerase (Pol-8) and processivity
      factor (PF-8) of KSHV were cloned recently. It was shown that PF-8 forms
      specifically a complex with Pol-8 in vitro and allows it to synthesize fully
      extended DNA. Since both Pol-8 and PF-8 are apparently essential for viral DNA
      replication and since they cannot be substituted by any other cellular or viral
      proteins, they are potentially excellent antiviral targets. The development of a
      mechanistic plate assay is now described, which is suitable for rapid high
      throughput screening of antiviral agents against Pol-8 and PF-8. The assay allows
      the measurement of not only total DNA synthesis activity (i.e. nucleotide
      incorporation) but also processivity (i.e. fully-extended DNA product). In this
      plate assay, any of the screen-compounds with an inhibitory effect against the
      total DNA synthesis activity and/or the processivity could be potential antiviral
      agents that target Pol-8 and/or PF-8. Particularly, since PF-8 is highly specific
      for Pol-8, the discovery of inhibitory agents against PF-8 may lead to specific
      antiviral therapies with minimal toxicity to host cells. This assay should be
      suitable for screening for inhibitory compounds against polymerases and
      processivity factors of other herpesviruses as well.

PMID- 10960710
TI  - Graphical approaches to support the analysis of linear-multilevel models of lamb
      pre-weaning growth in Kolda (Senegal).
AB  - Linear-multilevel models (LMM) are mixed-effects models in which several levels
      of grouping may be specified (village, herd, animal, ellipsis). This study
      highlighted the usefulness of graphical methods in their analysis through: (1)
      the choice of the fixed and random effects and their structure, (2) the
      assessment of goodness-of-fit and (3) distributional assumptions for random
      effects and residuals. An LMM was developed to study the effect of ewe deworming
      with morantel on lamb pre-weaning growth in a field experiment involving 182
      lambs in 45 herds and 10 villages in Kolda, Senegal. Growth was described as a
      quadratic polynomial of age. Other covariates were sex, litter-size and
      treatment. The choice of fixed and random effects relied on three graphs: (1) a
      trellis display of mean live-weight vs. age, to select main effects and
      interactions (fixed effects); (2) a trellis display of individual growth curves,
      to decide which growth-curve terms should be included as random effects and (3) a
      scatter plot of parameters of lamb-specific regressions (live-weight vs.
      quadratic polynomial of age) to choose the random-effects covariance
      structure.Age, litter-size, agexlitter-size, litter-sizextreatment and agexlitter
      sizextreatment were selected graphically as fixed effects and were significant
      (p<0.05) in subsequent statistical models. The selection of random-effect
      structures was guided by graphical assessment and comparison of the Akaike's
      information criterion for different models. The final random-effects selected
      included no random effect at the village level but intercept, age and squared-age
      at the herd and lamb levels. The structure of the random-effects variance
      covariance matrices were blocked-diagonal at the herd level and unstructured at
      the lamb level. An order-1 autoregressive structure was retained to account for
      serial correlations of residuals. Smaller residual variance at 90 days than at
      younger ages was modeled with a dummy variable taking a value of 1 at 90 days and
      0 elsewhere.Ewe-deworming with morantel during the rainy season lead to higher
      lamb live-weights (probably related to a better ewe-nutrition and -health
      status). A positive correlation was demonstrated between early weight and growth
      rate at the population level (with important lamb and herd-level random
      deviations). The persistence of this correlation at older ages should be checked
      to determine whether early weights are good predictors of mature weights and ewe
      reproductive lifetime performance.

PMID- 10960711
TI  - Retrospective analysis of trends and production factors associated with sow
      mortality on swine-breeding farms in USA.
AB  - Of the 825 pig farms in USA that mailed in their electronic file containing
      production records, 604 farms were used to observe breeding-female mortality risk
      and related factors (herd size, lactation length, parity and season). Multiple
      regression was used to determine factors associated with annual mortality risk.
      Analyses of variance were used for comparisons of mortality risks among parity
      and season groups. Average annual mortality risks during the 1997 period was
      5.68%. Average breeding-female inventories and average lactation length on USA
      farms were 733 and 18.3 days, respectively. Higher annual breeding-female
      mortality risk was associated with larger herd size, greater parity at farrowing
      and shorter lactation length (P<0.02). For example, as herd size increases by 500
      females, mortality risk increases by 0.44%. Older parity was associated with
      higher mortality risks. Summer season was also associated with higher mortality
      risk. Using five-years' records on 270 farms, annual mortality risk in 1997 was
      higher than those of 1993 and 1994, while average breeding-female inventory
      increased and lactation length decreased. It is recommended that producers,
      especially in large herds, pay more attention to breeding females.

PMID- 10960712
TI  - Risk factors for Brucella spp. infection In dairy cattle farms in Asmara, State
      of Eritrea.
AB  - A cross-sectional study was conducted to identify risk factors for herd infection
      by Brucella spp. in dairy cattle in the suburbs of Asmara, Eritrea. Data were
      collected from 64 herds, randomly selected from a total of 99 herds with a
      minimum herd size of 9 cows. A questionnaire was used to gather data on
      management, hygiene and herd structure. Serum samples collected from all pregnant
      heifers, cows and bulls, were screened for Brucella infection by the Rose Bengal
      test (RBT), and all RBT-positive sera re-tested with the complement-fixation test
      (CFT) for confirmation. A seropositive herd was defined as one in which at least
      one animal tested positive in the CFT. There were 23 (36%) positive herds among
      the 64 studied. Both multiple logistic and multiple betabinomial regression
      modeling were used to analyze the data. Mixed-breed herds, compared to single
      (exotic)-breed herds, were found to be independently associated with increased
      herd seroprevalence (OR=5.2, 95% confidence interval 1. 4-18.7) in the multiple
      logistic model with the herd infection status as the dependent variable. The
      importance of this variable was supported by the multiple betabinomial regression
      model (OR=3.3, 1.4-7.6) with animal-level prevalence within herd as the outcome
      variable. Both models also revealed the presence of a negative association
      between seropositivity and cattle stocking density.

PMID- 10960713
TI  - Antimicrobial-resistance trends in bacterial isolates from companion-animal
      community practice in the UK.
AB  - We conducted a longitudinal, retrospective investigation of antimicrobial
      resistance in bacterial isolates obtained from canine and feline clinical cases
      in veterinary community practice in UK (1989-1997). Individual-drug resistance
      was examined using isolates of Escherichia coli and Staphylococcus spp. as Gram
      negative and Gram-positive indicator organisms, respectively. The annual
      prevalence of resistance was calculated for each organism to each of nine (for E.
      coli) and 11 (for Staphylococcus spp.) selected antimicrobials. The annual
      prevalence of multiple-drug resistance (MDR) was calculated for E. coli, Proteus
      spp., Pseudomonas spp., staphylococci and streptococci. Using a chi-square test
      for trend, significant rising trends were identified in individual resistance of
      E. coli to clavulanate-amoxycillin and streptomycin, and in MDR of E. coli,
      Proteus spp. and Pseudomonas spp. Declining trends were identified in individual
      resistance of Staphylococcus spp. to ampicillin and penicillin. Comparison with
      previously reported results from a contemporaneous investigation of companion
      animal hospital patients indicated that selection pressures acting on the two
      populations overlapped but were not identical.

PMID- 10960714
TI  - Prevalence of intestinal pathogens in Danish finishing pig herds.
AB  - Our aim was to determine the prevalence of the intestinal bacteria: Lawsonia
      intracellularis, Brachyspira hyodysenteriae, Serpulina intermedia, Brachyspira
      innocens, Brachyspira pilosicoli, pathogenic Escherichia coli (serogroups O138,
      O139, O141 and O149) and Salmonella enterica in Danish finishing pig herds. A
      total of 79 herds was randomly selected and visited during 1998. From each herd,
      20 faecal samples were collected from individual pigs weighing 30-50kg.
      Furthermore, 10 pooled pen samples were collected and examined for S. enterica.
      In total, 1580 faecal samples and 790 pen samples were collected and examined by
      polymerase chain reaction (PCR) or culture. L. intracellularis was found in 74
      herds (93.7%), B. hyodysenteriae in two herds (2.5%), S. intermedia in 10 herds
      (12. 7%), B. innocens in 27 herds (34.2%), B. pilosicoli in 15 herds (19. 0%),
      pathogenic E. coli in 19 herds (24.1%) and S. enterica in eight herds (10.1%).
      The within-herd prevalences of L. intracellularis and B. hyodysenteriae were 25
      30%; the within-herd prevalences of the other agents were 5-10%. Three herds (4%)
      were not infected with any of the bacteria and 25 herds (32%) were only infected
      with L. intracellularis.

PMID- 10960715
TI  - Seroprevalence of porcine respiratory coronavirus in selected Korean pigs.
AB  - A total of 446 serum samples from 88 herds in Korea were examined for antibody to
      porcine respiratory coronavirus (PRCV) using blocking enzyme-linked immunosorbent
      assay (ELISA). All serum samples were collected from 24- to 26-week-old finishing
      pigs between December 1998 and June 1999. By ELISA, 237 out of 446 sera tested
      (53.1%) and 54 out of 88 sampled herds (61.3%) were positive against PRCV. Of 446
      sera from 88 herd tested, 185 (41.5%) serum samples from 22 (25%) herds were
      seronegative against PRCV and transmissible gastroenteritis virus infection. Our
      data suggested that seropositive herds for PRCV are distributed diffusely
      throughout South Korea.

PMID- 10960716
TI  - Corrigendum to "Bulk-tank milk ELISA antibodies for estimating the prevalence of
      paratuberculosis in danish dairy herds".

PMID- 10960717
TI  - Effects of 15-month aldose reductase inhibition with fidarestat on the
      experimental diabetic neuropathy in rats.
AB  - We examined the effects of long-term treatment with an aldose reductase inhibitor
      (ARI) fidarestat on functional, morphological and metabolic changes in the
      peripheral nerve of 15-month diabetic rats induced by streptozotocin (STZ).
      Slowed F-wave, motor nerve and sensory nerve conduction velocities were corrected
      dose-dependently in fidarestat-treated diabetic rats. Morphometric analysis of
      myelinated fibers demonstrated that frequencies of abnormal fibers such as
      paranodal demyelination and axonal degeneration were reduced to the extent of
      normal levels by fidarestat-treatment. Axonal atrophy, distorted axon circularity
      and reduction of myelin sheath thickness were also inhibited. These effects were
      associated with normalization of increased levels of sorbitol and fructose and
      decreased level of myo-inositol in the peripheral nerve by fidarestat. Thus, the
      results demonstrated that long-term treatment with fidarestat substantially
      inhibited the functional and structural progression of diabetic neuropathy with
      inhibition of increased polyol pathway flux in diabetic rats.

PMID- 10960718
TI  - Cost and resource utilization for prevention and treatment of foot lesions in a
      diabetic foot clinic in Belgium.
AB  - This prospective observational study was carried out to assess the annual
      preventive and curative treatment costs for diabetic foot problems. Measures of
      resource use over the 1-year study period were taken for 151 patients whose
      lesions covered the entire Wagner classification. Treatment was provided under
      the current protocols of a multidisciplinary team. The 1993 market prices for
      health services were used to convert units of health service utilization to
      expenditures by the social insurance system and the patients. The severity of the
      foot problems determined the medical cost. Preventive care (47 cases),
      represented an average cost per case of US$ 880 (1US$ 1993=BEF 30.65). Curative
      care (120 cases), including diagnostic tests, wound dressings, antibiotic
      therapy, revascularization and off loading techniques resulted in a mean cost of
      US$ 5227 per ulcer. Care for the 16 most severe wounds and amputations involved
      hospitalization and surgery at a mean cost per ulcer of US$ 31716. The most
      important cost contributers were hospitalizations (72%), drugs (11%) and
      diagnostic examinations (4%). Preventive treatment for diabetic foot problems can
      represent a significant saving for the social insurance system as well as for the
      patients.

PMID- 10960719
TI  - The influence of traditional Chinese herbal drugs on serum 1, 5-anhydroglucitol
      levels.
AB  - The serum concentration of 1,5-anhydroglucitol (1,5-AG), a polyol which
      originates mainly in the diet, is used in Japan as a new marker for glycemia. To
      evaluate the potential interference of 1, 5-AG measurements by traditional
      Chinese medicines (Kampo), we examined the 1,5-AG content in 32 types of
      concentrated dosage forms of Kampo using high performance liquid chromatography
      (HPLC). The 32 types of Kampo were the most frequently used in Japan, two of
      which, Ninjin-yoei-to (7030 microg/g dry weight) and Kami-kihi-to (6700 microg/g
      dry weight), contained large amounts of 1,5-AG. Six others contained small
      amounts of 1,5-AG. Both Ninjin-yoei-to and Kami-kihi-to contain the same
      ingredient, Polygalae radix, which is a crude form of polygalitol (1,5-AG). To
      confirm the effects of these Kampo medicines on the serum levels of 1,5-AG, we
      administered Ninjin-yoei-to (7.5 g/day) for 8 weeks to 18 patients with Type 2
      diabetes mellitus (Type 2 DM). The serum level of 1,5-AG increased from 9.8+/-8.9
      to 28.1+/-17.5 microg/ml by week 8. Hemoglobin A1c (HbA1c) had not changed by
      week 8. Thus, an abnormal serum 1,5-AG level may be present in patients taking
      Kampo which contains Polygalae radix.

PMID- 10960720
TI  - Smoking, blood glucose control, and locus of control beliefs in people with type
      1 diabetes mellitus.
AB  - The relations between blood glucose control (HbA(1c)), smoking, and health
      related diabetes locus of control beliefs were studied in a consecutive adult
      sample of 187 patients with Type 1 diabetes who were free of diabetes
      complications. Those who were smokers (n=32) had poorer HbA(1c) values than non
      smokers [7.5+/-1.4 (S.D.) vs 6. 8+/-1.2%, P=0.017]. When the patients were
      compared according to HbA(1c) quartiles, 17 of the smokers (53%) were found among
      those with worst blood glucose control. The smokers showed a lesser belief than
      the non-smokers in powerful others such as physicians and diabetes nurses in
      regards as diabetes control and the course of the disease [23.5+/-4.4 (S.D.) vs
      25.8+/-5.5 (S.D.), P=0.05]. The group as a whole exhibited strong beliefs that
      their own behaviour was important for diabetes control. This belief appears
      incongruent with smoking behaviour. The results have implications for possible
      coping and defence strategies used by the smokers. Due to their worse blood
      glucose control, weaker beliefs in health care professionals, and possible denial
      like coping strategies, smokers clearly need special attention in diabetes care,
      particularly in the view of their risk of developing long-term complications.

PMID- 10960721
TI  - Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by
      ventilatory threshold.
AB  - Prescription of aerobic exercise for Type 2 diabetes mellitus (Type 2 DM) in
      clinical practice is frequently based on exercise intensity at maximum heart rate
      (60<HR(max)<79%), heart rate reserve (50<HR(reserve)<74%), and rating of
      perceived exertion (12<RPE<13). We examined these parameters in Japanese males
      with Type 2 DM at ventilatory threshold (VT) to investigate the exercise capacity
      of Type 2 DM patients and re-evaluate the exercise prescription. Fifty-six
      Japanese Type 2 DM males without autonomic neuropathy [age, 53.5+/-7.7 years;
      body mass index (BMI), 23.7+/-3.6 kg/m(2)] were enrolled and compared with 56 age
      and BMI-matched healthy Japanese males. VT was determined breath by breath
      during exercise test using a ramp protocol and rates of oxygen consumption
      (VO(2)), work rate (WR), HR, DeltaHR, %HR(max), %HR(reserve), and RPE were
      measured at VT. Type 2 DM patients had significantly lower VO(2) (3.6+/-0.4
      metabolic equivalents (METs)) and WR (62+/-14 W) than controls (VO(2), 3.9+/-0.6
      METs; WR, 74+/-13 W). %HR(reserve), (32.6+/-7.7%) was also significantly lower
      compared with controls (37.6+/-8.3%), while %HR(max), was not different. RPE was
      also similar in diabetics (12.4+/-1.5) and controls (12.9+/-1.2), however, it was
      significantly lower in diabetic patients aged 60-69 years (11.8+/-2.0) and those
      with distal symmetric sensory neuropathy (12.2+/-1.0). Our results indicate
      reduced exercise capacity in Japanese Type 2 DM males and the exercise intensity
      of 60%HR(max), 30%HR(reserve), and RPE 12 is recommended in elderly diabetics and
      those with diabetic sensory neuropathy.

PMID- 10960722
TI  - Parallel changes of proinsulin and islet amyloid polypeptide in glucose
      intolerance.
AB  - Elevated proinsulin secretion and islet amyloid deposition are both features of
      Type 2 diabetes but their relationship to beta-cell dysfunction is unknown. To
      determine if islet amyloid polypeptide (IAPP) secretion is disproportionate with
      other beta-cell products at any stage of glucose intolerance, 116 subjects were
      studied. Non-diabetic subjects with equivalent body mass index (BMI) were
      assigned to three groups, (i) normal fasting glucose, fpg<5.5 mmol l(-1); (ii)
      intermediate fasting glucose, fpg> or =5.5<6.15 mmol l(-1); (iii) impaired
      fasting glucose (IFG), fpg> or =6.1<7.0 mmol l(-1). Diabetic subjects were
      divided according to therapy (9 diet, 19 tablet, and 11 insulin). IAPP, C-peptide
      and proinsulin were measured fasting and at the end of a 1-h glucose infusion.
      Fasting C-peptide, IAPP and proinsulin were significantly elevated in the IFG
      group compared with the other non-diabetic groups (P<0.02); fasting IAPP/C
      peptide and proinsulin/C-peptide were 1-2% in all non-diabetic groups. Fasting
      and 1-h proinsulin and proinsulin/C-peptide were higher in diabetic compared with
      non-diabetic subjects (P<0.01). IAPP and IAPP/C-peptide in diabetic groups were
      similar to that in non-diabetic subjects but reduced in the insulin-treated group
      (P<0.01). Proinsulin was disproportionately increased compared with C-peptide and
      IAPP in Type 2 diabetes particularly in severe beta-cell failure implying more
      than one concurrent beta-cell pathology.

PMID- 10960723
TI  - Increased plasma endothelin-1 and intraplatelet cyclic guanosine monophosphate in
      men with disturbed glucose metabolism.
AB  - Plasma endothelin-1, the nitric oxide (NO) mediator intraplatelet cyclic
      guanosine monophosphate (cGMP), the prostacyclin mediator cyclic adenosine
      monophosphate (cAMP) and the macrophage derived inflammatory mediator plasma
      neopterin were measured in men with Type 2 diabetes mellitus (n=91), impaired
      glucose tolerance (IGT; n=51), previously abnormal glucose tolerance (PAGT;
      n=20), and 34 healthy control men. Plasma endothelin-1was higher in men with Type
      2 diabetes mellitus than in controls [4.1 (1.0-14.3) vs. 2.1 (0.2-8. 7) ng/l;
      P<0.001). Intraplatelet cGMP was higher in men with PAGT [0. 84 (0.57-2.76)
      pmol/10(9) platelets; P<0.05], IGT [0.85 (0.48-3.53); P<0.001] and Type 2
      diabetes mellitus [0.90 (0.47-3.86); P<0.001] than in controls [0.70 (0.42-1.70].
      No differences existed between groups concerning intraplatelet cAMP or plasma
      neopterin. Plasma endothelin-1 correlated with fasting plasma glucose (r=0.33;
      P<0.001) and HbA1(c) (r=0.29; P<0.001). In conclusion, elevated plasma endothelin
      1 in Type 2 diabetes mellitus and its relationship to glucose and HbA1(c) suggest
      a putative role for endothelin-1 in diabetic endothelial cell damage. Increased
      cGMP indicating enhanced production/activity of NO suggests that factors other
      than reduced NO activity contribute to enhanced platelet aggregation in diabetes.

PMID- 10960724
TI  - Increased risk of cardiovascular disease in newly diagnosed type 2 diabetic
      patients in a primary health care center in Trinidad.
AB  - The prevalence of cardiovascular diseases (CVD) has increased sharply in the
      developing countries and because Type 2 diabetic patients are at increased risk
      for CVD, we assessed CVD risk factors in newly diagnosed Type 2 diabetic patients
      presenting in a primary health care center in Trinidad. Fasting and 2 h
      postprandial blood samples were collected from 387 (269 females, 118 males) newly
      diagnosed Type 2 diabetic patients (mean age: 53.1+/-6.6 years) for the
      determination of plasma glucose, creatinine, cholesterol (chol), triglyceride
      (TG) and % glycated hemoglobin (HbA(1c)) concentrations. Blood pressure and
      anthropometric indices were also measured. There were high prevalence rates of
      obesity (37%), overweight (35%), hypertension (21%), hypercholesterolemia (25%)
      and hypertriglyceridemia (22.3%) among the patients and these were significantly
      higher in women than men (P<0.001). Patients of Indian descent had a
      significantly higher prevalence of diastolic hypertension and
      hypertriglyceridemia compared with patients of African origin or mixed race
      (P<0.001). In comparison with males, female diabetic patients were at greater
      risk of cardiovascular morbidity and mortality. Early detection of CVD risk
      factors and treatment, particularly in women, may be beneficial management
      strategy in all local diabetic clinics in Trinidad.

PMID- 10960725
TI  - Age of onset, not type of onset, affects the positivity and evanescence of IA-2
      antibody.
AB  - Autoantibody against IA-2 (IA-2A) was found to be discordant with autoantibody
      against glutamic acid decarboxylase (GADA) with respect to both positivity and
      titer in Japanese, the same as in Caucasians. In this study, 247 type 1 diabetic
      patients were tested in order to clarify how the type of onset, age of onset, and
      duration of diabetes affect the frequency and evanescence of IA-2A. Among the
      young onset patients, the frequency of IA-2A was higher (52.2%), but evanescent
      (54.5, 66.7 and 36.7% in the insulin therapy duration < or =1, 2-5 years, and >
      or =6 years groups, respectively), whereas among adult onset patients, the
      frequency was lower (19.3%) but persistent (19.6, 13.3 and 23.5%, respectively).
      In addition, in the follow-up study, two of three IA-2A-positive young onset
      patients converted to negative in only three years, while all five adult onset
      patients remained positive for over 5 years. Among the adult onset patients, IA
      2A frequency was similar in the slowly progressive type and the abrupt onset
      type. In view of the above findings, IA-2A positivity and evanescence in type 1
      diabetic patients appear to be affected by age of onset, not type of onset.

PMID- 10960726
TI  - Reduced pulmonary function and its associations in type 2 diabetes: the Fremantle
      Diabetes Study.
AB  - To determine whether diabetes is associated with reduced lung function, we
      studied 421 Anglo-Celt/European subjects, representing 20.5% of all patients with
      type 2 diabetes identified in an urban Australian catchment area of 120097
      people. In addition to collection of detailed demographic and diabetes-specific
      data, spirometry was performed and forced vital capacity (FVC), forced expiratory
      volume in 1 s (FEV1), vital capacity (VC) and peak expiratory flow (PEF)
      measured. When expressed as a percentage of those predicted (%pred) for age, sex
      and height, the means of all spirometric measures were reduced by > or =9.5%.
      After controlling for smoking, age and gender in a linear regression model,
      HbA(1c) was not associated with any measure of lung function (P>0.13) but
      diabetes duration was significantly associated with FEV1(%pred) and PEF(%pred)
      (P< or =0.04) and had borderline associations with FVC(%pred) and VC(%pred) (P<
      or =0.064). In separate analyses controlling for smoking alone, age, body mass
      index (BMI), coronary heart disease (CHD) and retinopathy were independently and
      inversely associated with FVC(%pred), FEV1(%pred) and VC(%pred) (P<0.05). In sub
      group analyses, these three spirometric measures were associated with BMI, CHD
      and diabetes duration in males, and age and BMI in females. Pulmonary function is
      reduced in type 2 diabetes. Diabetes duration seems a more important influence
      than glycaemic control, but obesity and vascular disease may also contribute.

PMID- 10960727
TI  - The debranching enzyme complex missing in glycogen accumulating mutants of
      Chlamydomonas reinhardtii displays an isoamylase-type specificity.
AB  - To investigate the functions of debranching enzymes in starch biosynthesis, we
      have partially purified and characterized these activities from wild type and
      mutant sta7 Chlamydomonas reinhardtii. Mutants of the STA7 locus substitute
      synthesis of insoluble granular starch by that of small amounts of glycogen-like
      material. The mutants were previously shown to lack an 88 kDa debranching enzyme.
      Two distinct debranching activities were detected in wild-type strains. The 88
      kDa debranching enzyme subunit missing in glycogen-producing mutants (CIS1) is
      shown to be part of a multimeric enzyme complex. A monomeric 95 kDa debranching
      enzyme (CLD1) cleaved alpha-1,6 linkages separated by as few as three glucose
      residues while the multimeric complex was unable to do so. Both enzymes were able
      to debranch amylopectin while the alpha-1,6 linkages of glycogen were completely
      debranched by the multimeric complex only. Therefore CLD1 and the multimeric
      debranching enzyme display respectively the limit-dextrinase (pullulanase) and
      isoamylase-type specificities. Various mutations in the STA7 locus caused the
      loss of both CIS1 and of the multimeric isoamylase complex. In contrast to rice
      and maize mutants that accumulate phytoglycogen owing to mutation of an
      isoamylase-type DBE, isoamylase depletion in Chlamydomonas did not result in any
      qualitative or quantitative difference in pullulanase activity.

PMID- 10960728
TI  - A rapid and sensitive assay method for measuring amine oxidase based on hydrogen
      peroxide-titanium complex formation.
AB  - Hydrogenperoxide (H(2)O(2)) is an end product of diamine and polyamine oxidation
      by their respective oxidase enzymes. A new sensitive assay method is based on a
      H(2)O(2)-titanium (Ti) complex formation as an indicator of H(2)O(2) production
      due to polyamine oxidation. The orange-yellow coloured H(2)O(2)-Ti complex was
      measured at 410 nm in a Shimadzu spectrophotometer. The assay conditions for
      maximum diamine oxidase (DAO) and polyamine oxidase (PAO) as standardized here
      using the hypocotyl tissues of Vigna catjang Endl. cv Pusa Barsati consisted of
      pH 7.4 (40 mM potassium phosphate buffer), 3 mM substrate (putrescine or
      spermine), 37 degrees C incubation temperature and 30 min incubation time in the
      presence of catechol (10(-2) M) used as an inhibitor of both peroxidase and
      catalase activity. The method described here was significantly more sensitive
      than the starch-iodide method [T.A. Smith, Biochem. Biophys. Res. Commun. 41
      (1970) 1452-1456], which could be improved further if measured under the same
      assay conditions as described for the H(2)O(2)-Ti method. Sensitivity of the
      present method was tested by assaying DAO/PAO activity in auxin treated
      hypocotyls of Vigna and comparing it with the starch-iodide method in two other
      plant samples.

PMID- 10960729
TI  - Changes in lipid composition during somatic embryogenesis in leaves of Cichorium.
AB  - The present studies were conducted to investigate the changes in lipid and fatty
      acid composition during the earliest stages of somatic embryogenesis in leaf
      tissues of the Cichorium hybrid '474'. The presence of glycerol in the culture
      medium during the induction step allowed to separate two phases in the
      embryogenic process. Firstly, cells are induced for morphogenetic competence
      (induction phase) and secondly, they express an embryogenic competence
      (expression phase). The analysis of fatty acid composition of total lipids showed
      that the percentage of linolenic acid (18:3) decreased while that of linoleic
      acid (18:2) increased throughout the culture period. A comparison with a non
      embryogenic genotype of Cichorium indicated a higher increase of linoleate
      content in embryogenic genotype. The incorporation of [14C] glycerol into lipid
      classes was studied in leaf tissues. During the induction step, label was
      confined almost exclusively in polar lipids, particularly in phosphatidylcholine
      (PC). An important increase of labeled triacylglycerols (TAG) amounts was noted
      during the expression step. The accumulation of 18:2 was observed in PC and also
      in TAG. These results show that the early stages of somatic embryogenesis are
      associated with the increase of PC and TAG which are mainly enriched in 18:2.

PMID- 10960730
TI  - Nitric oxide induces cell death in Taxus cells.
AB  - Sodium nitroprusside (SNP), a nitric oxide donor, or centrifugation at 150 times
      unit gravity, caused a nitric oxide burst in oocyte-derived Taxus brevifolia
      haploid cultures. This burst, visualized by the specific fluorescent probe 4,5
      diaminofluorescein diacetate (DAF-2 DA), preceded a significant increase in
      nuclear DNA fragmentation and cell death. DNA fragmentation was detected in situ
      by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      (TUNEL) of DNA 3'-OH groups. Nitric oxide formation and cell death were
      significantly decreased by N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide
      synthase (NOS; EC 1.14.13.39) inhibitor. Our results show that nitric oxide leads
      to irreversible DNA fragmentation and cell death under stressful conditions, and
      that its effect can be prevented by L-NMMA.

PMID- 10960731
TI  - The octadecanoid pathway is required for pathogen-induced multi-functional acetyl
      CoA carboxylase accumulation in common bean (Phaseolus vulgaris L.).
AB  - A partial cDNA clone corresponding to the multi-functional acetyl-CoA carboxylase
      (ACCase, EC 6.4.1.2) was isolated using RNA extracted from methyl jasmonate
      (MeJA)-induced common bean cell cultures. Most of this clone corresponds to the
      3' untranslated region and it showed high identity to alfalfa and soybean ACCase
      sequences. Southern hybridization revealed one copy of this gene in the common
      bean genome. In addition to being induced by MeJA in cell cultures and leaves,
      ACCase mRNA accumulated after yeast elicitor or Pseudomonas syringae pv tabaci
      treatment. Inhibitors of the octadecanoid pathway severely reduced ACCase mRNA
      and protein accumulation induced by yeast elicitor or P. syringae pv tabaci,
      indicating that jasmonates or a precursor mediate ACCase induction after pathogen
      infection. These results provide a role for the eukaryotic ACCase during the
      defense response to pathogens in common bean.

PMID- 10960732
TI  - Seed storage protein composition of non-nodulating soybean (Glycine max (L.)
      Merr.) and its influence on protein quality.
AB  - A 53 kDa protein, which accumulates at low levels in non-nodulating Clark
      soybeans, was purified by preparative sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). Polyclonal antibodies were raised against the gel
      purified protein. N-terminal sequence analysis identified the 53 kDa protein as
      the beta-subunit of beta-conglycinin. Results from Western blot analysis, using
      antibodies raised against the purified beta-subunit of beta-conglycinin, revealed
      that accumulation of this protein was enhanced in non-nodulating soybeans when
      the plants were supplemented with nitrogen. Results from Northern blot analysis
      indicate that non-nodulating soybeans in general had lower levels of mRNA for the
      major soybean seed proteins. A one-time application of nitrogen to non-nodulating
      soybeans enhanced the accumulation of the 1.6 kb beta-conglycinin beta-subunit
      mRNA. The mRNA levels of the 2.1 kb beta-conglycinin alpha'-subunit and the 2.2
      kb G4 glycinin in the non-nodulating soybeans were several-fold lower than in
      nodulating soybeans. Nitrogen application had no effect on the abundance of these
      RNA transcripts. The amount of RNA encoding an 8.5 kDa sulfur-rich protein was
      two-fold higher in non-nodulating soybeans when compared with nodulated soybeans.
      Nitrogen application reduced the abundance of this transcript to levels
      comparable with those of nodulated soybeans. Despite lower levels of the beta
      subunit of beta-conglycinin, the methionine content of the total seed protein
      fraction was lower than that of nodulated soybeans. In contrast, non-nodulating
      soybeans contained more cysteine than nodulating soybeans.

PMID- 10960733
TI  - Transgenic expression of the TRI101 or PDR5 gene increases resistance of tobacco
      to the phytotoxic effects of the trichothecene 4,15-diacetoxyscirpenol.
AB  - Mycotoxins are fungal secondary compounds that are toxic to vertebrates. Their
      presence in food and feeds, as the result of fungal disease in crops, can present
      a danger to animal or human health. Many mycotoxins have also been shown to be
      phytotoxic and in some cases, such as with trichothecenes produced by the wheat
      head blight fungus Fusarium graminearum, mycotoxins may act as virulence factors.
      Antibiotic-producing organisms, including fungi, protect themselves from their
      own toxins by metabolic alteration of the compound, modification of the target
      site of action or by exporting the compound to the extracellular space. We have
      tested the effectiveness of adapting two of these strategies, metabolic
      alteration and extracellular transport, to protect plant cells from the
      deleterious effects of the trichothecene 4,15-diacetoxyscirpenol (DAS). Tobacco
      plants were transformed with either the Saccharomyces cerevisiae gene PDR5, which
      encodes a multi-drug transporter, or with the Fusarium sporotrichioides gene
      TRI101, which encodes a trichothecene 3-O-acetyltransferase. Both genes conferred
      significant increased tolerance to DAS as measured by a sensitive seed
      germination assay. Expression of PDR5 or TRI101 in a seed-specific manner in crop
      plants such as wheat could lower the incidence of head blight as well as reduce
      mycotoxin levels within the seed.

PMID- 10960734
TI  - Additional phosphate stabilises uninterrupted growth of a Dioscorea deltoidea
      cell culture.
AB  - Suspension cells of Dioscorea deltoidea Wall (strain D-1) were maintained in a
      semicontinuous culture (SCC) in shake flasks at a high growth rate. It was shown
      that continuous propagation growth of this culture is unstable on Murashige's and
      Skoog's (MS) medium due to P starvation. On a P-enriched MS-medium the SCC was
      stable even at mean specific growth rates >0.3 day(-1). Highest volumetric
      concentrations of furostanol glycosides were obtained, when a P-enriched SCC was
      not further subcultivated but fed with sucrose. The investigated culture is able
      to control phosphate uptake and to prevent toxicity on media with excess P. High
      concentrations of cellular P(i) did not effect the ratio of furostanol to starch.

PMID- 10960735
TI  - Unusual arrangement of catalytic domains in head-to-tail associated homodimer of
      6-hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme.
AB  - 6-Hydroxymellein synthase, a multifunctional polyketide synthetic enzyme in
      carrot, is organized as a homodimer, and the activity of the synthase was
      appreciably inhibited upon the specific alkylation of cysteine- and cysteamine
      SHs at the reaction center with iodoacetoamide and chloroacetyl-CoA,
      respectively. Dissociation and stoichiometric recombination of the unmodified and
      the SH-modified enzyme subunits yielded a combination of unmodified-unmodified,
      unmodified-modified and modified-modified hybrid dimers that together exhibit 50%
      activity. In contrast, hybrid dimers obtained by reconstruction of the two
      modified enzymes showed essentially no catalytic activity. These results suggest
      that the two subunits of 6-hydroxymellein synthase are aligned in head-to-tail
      orientation to organize two reaction centers which are comprised of a cysteine
      and a complementary cysteamine SH group, belonging to and contributed from the
      same subunit in the homodimer structure.

PMID- 10960736
TI  - A combination of vermiculite and paper pulp supporting material for the
      photoautotrophic micropropagation of sweet potato.
AB  - A mixture of vermiculite (hydrous silicates) and paper pulp (waste product of
      paper industry) was used as a supporting material for the in vitro
      photoautotrophic micropropagation of plantlets. Sweet potato was used as a model
      plant to find out the appropriate proportion of vermiculite and paper pulp for
      the optimum growth of the plantlets. The plantlets grown in the conventional
      supporting material, agar, were used as the control. The study revealed that in
      all aspects, the plantlets grown in vermiculite mixed with 30% (w/w) paper pulp
      exhibited the highest growth performance. The shoot and root fresh mass were x2.7
      greater than those in agar (control); the leaf, stem and root dry mass were also
      greater and at least two fold in this treatment compared with those in the
      control. The net photosynthetic rate per plantlet was highest in this treatment,
      and on day 20 it was 15.3 umol CO(2) h(-1) as compared with 9.8 umol CO(2) h(-1)
      in the control. The growth of both shoots and roots decreased gradually with the
      increase or decrease of percentage of paper pulp in the supporting material. In
      general, the growth was significantly poorer in the plantlets grown in 100%
      vermiculite than that in vermiculite mixed with 30% paper pulp but still greater
      than in the control. The porosity of the supporting materials increased with the
      increase in the percentage of paper pulp in the supporting material. After
      transplanting to the ex vitro condition the survival percentage did not vary
      significantly (90-100%) among the treatments, except in control where it was only
      73%. The number of unfolded leaves and the stem height were similar among the
      treatments except those in the control.

PMID- 10960737
TI  - Effects of mild night chilling on respiration of expanding cotton leaves.
AB  - Utilizing expanding leaves of cotton (Gossypium hirsutum L. cv. Coker 312), the
      hypothesis that suboptimal night temperatures above those for putative phase
      transitions of mitochondrial lipids caused greater substrate control of night
      respiration and increased the control that respiration exerted on ATP-dependent
      metabolism was tested. Night respiratory CO(2) evolution rates for 5-7-day-old
      leaves growing at 30/19 degrees (day/night) nearly equaled those of leaves
      exposed to 28 degrees C nights, while leaves exposed to 15 degrees C nights had
      rates that were 42% of those at 28 degrees C. No restriction of respiration by
      carbohydrate supply was detected for leaves grown at either cool night
      temperature or when warm-grown plants were transferred to cool night conditions.
      Pyruvate utilization was more sensitive to mild chilling than glycolysis. Growth
      at 30/19 or 30/15 degrees C resulted in higher nocturnal ATP:ADP and energy
      charge for expanding leaves than growth at 30/28 degrees C, suggesting a
      lessening of respiratory control of ATP-dependent metabolism with long-term night
      chilling. However, cool night exposure resulted in reductions in total
      phosphorylated adenylates, and the low ATP content, most notably occurring during
      15 degrees C nights, may have restricted some metabolic activity. The cause of
      these low ATP levels and their possible effects on cotton metabolism during
      chilling remain to be elucidated.

PMID- 10960738
TI  - Promoter analysis of pyk20, a gene from Arabidopsis thaliana.
AB  - The gene pyk20 which has been isolated from Arabidopsis thaliana encodes a
      protein with a glutamine-rich domain in the C-terminal region. The transcription
      of this gene was shown to be induced in feeding sites of root-parasitic nematodes
      (Heterodera schachtii), in roots infected by a fungus-like organism
      (Plasmodiophora brassicae), by plant hormone treatment, and by wounding. In order
      to identify functional promoter regions seven different 5' and 3' pyk20 promoter
      (ppyk20) deletion fragments were fused to the uidA gene (gus) and transformed
      into A. thaliana plants. Histochemical analysis of plants containing the
      different ppyk20::uidA reporter constructs was performed during plant development
      in different plant tissues. Comparison of the promoter deletion constructs showed
      that the region between -277 and -1 bp is necessary to enhance the level of the
      GUS expression in nematode feeding sites and by plant hormone treatment. The
      region between -1912 and -278 is essential to provide specificity of GUS
      expression. Conserved regulatory elements were identified in the ppyk20 by
      sequence analysis. The activation pattern of ppyk20 makes it well suited to
      engineer resistance against nematodes and other pathogens.

PMID- 10960739
TI  - Characterization of cell wall oxalate oxidase from maize roots.
AB  - Oxalate oxidase activity was detected in the cell wall fraction isolated from
      maize roots (Zea mays L.). The enzyme was active at acidic pH with optimal
      activity at pH 3.2. It was thermally extremely stable and resistant to high salt
      concentration, SDS and pepsin. The enzyme activity was inhibited by sulphydryl
      reagents 2-mercaptoethanol (2-ME), N-ethyl maleimide (NEM) and dithiotreitol
      (DTT), but was insensitive to EDTA, KCN and metal ions. Measurements of enzyme
      activity were performed using colorimetric assay of H(2)O(2), as well as
      polarographic detection of O(2) consumption. Maximal activity was obtained with 5
      mM oxalic acid for the colorimetric method, and 10 mM oxalic acid for the
      polarographic method. Both methods were applicable in oxalate oxidase
      characterization, the polarographic method being more suitable under conditions
      of H(2)O(2) interaction with some of the analyzed substances.

PMID- 10960740
TI  - 3D reconstruction based on hard tissue microtome cross-section pictures in
      dentistry.
AB  - The aim of this study was to examine the accuracy of the computerized 3D surface
      analyzing and volume measuring method in dentistry. Two different types of test
      objects were used in the first part of the measurements. Each sample of the two
      groups was cross-sectioned using a hard tissue microtome. The sections were
      photographed on both sides and were projected on a graphical tablet and analyzed
      using a computer program. The measured and calculated parameters were compared.
      In the second part, 200 microm thick horizontal sections were prepared from 11
      human incisor roots using the hard tissue microtome. This way, five sections were
      prepared from the apical 2 mm of each root. The effects of section thickness and
      number were modeled by decreasing the inclusion rate of the obtained number of
      sections from 10 to 2 and its influence on the calculated results was determined.
      This method was suitable for the approximation and analysis of 3D parameters. The
      results indicated that using 200-300 microm section thickness, the measured
      values were approximately 8-21% lower than the real parameters.

PMID- 10960741
TI  - Design and implementation of an Internet-based health information resource.
AB  - In support of its institutional mission of community service, the Medical College
      of Wisconsin created a digital library of health information. This Internet-based
      resource, named MCW HealthLink, provides health news and information geared to
      patients, their family members, and the community at large. Information is
      delivered through a World Wide Web site and an e-mail newsletter. The web and e
      mail components are integrated to maximize their utility to readers. This article
      describes the philosophy, design and implementation of the resource. Ongoing
      efforts include development of a health information resource tailored to the
      needs of individual readers.

PMID- 10960742
TI  - An add-in implementation of the RESAMPLING syntax under Microsoft EXCEL.
AB  - The RESAMPLING syntax defines a set of powerful commands, which allow the
      programming of probabilistic statistical models with few, easily memorized
      statements. This paper presents an implementation of the RESAMPLING syntax using
      Microsoft EXCEL with Microsoft WINDOWS(R) as a platform. Two examples are given
      to demonstrate typical applications of RESAMPLING in biomedicine. Details of the
      implementation with special emphasis on the programming environment are discussed
      at length. The add-in is available electronically to interested readers upon
      request. The use of the add-in facilitates numerical statistical analyses of data
      from within EXCEL in a comfortable way.

PMID- 10960743
TI  - Hippin: a semiautomatic computer program for selecting hip prosthesis femoral
      components.
AB  - This work illustrates a computer program designed to aid surgeons in selecting
      the hip prosthesis femoral component during the preoperation planning stage of
      hip replacement surgery. Starting from the processing of the patient's coxo
      femoral region X-ray image, the program, called Hippin, interacts with the user
      to outline the femoral region, including the head and the inner contour of the
      proximal femur. It automatically examines all possible couplings with the
      patient's femur outlines from a database containing the outlines of the available
      prostheses created by digitizing the templates normally used in preoperation
      planning. The resulting images enable the surgeon to visually compare all the
      alternatives. In addition, the program provides numerical values for the
      distances between the physiological rotation and prosthesis centers, helping the
      surgeon in selecting from among the possibilities. The program has been validated
      by comparing the computer results with actual surgeon selections.

PMID- 10960744
TI  - Detection of linear and nonlinear dependencies in time series using the method of
      surrogate data in S-PLUS.
AB  - A general implementation of the method of surrogate data in the S programming
      language for use with the S-PLUS statistical package is presented. We illustrate
      the application of the S functions to testing hypotheses about a human heart rate
      time series and demonstrate that there is evidence for both linear and nonlinear
      dependencies. We expect these S functions will be useful for the application of
      the method of surrogate data to the analysis of biomedical time series using the
      S-PLUS statistical software package.

PMID- 10960745
TI  - Automatic ectopic beat elimination in short-term heart rate variability
      measurement.
AB  - Our studies deal with fully automatic measurement of heart rate variability (HRV)
      in short term electrocardiograms. Presently, all existing HRV analysis programs
      require user intervention for ectopic beat identification, especially of
      supraventricular ectopic beats (SVE). This makes the HRV measurement in large,
      e.g. epidemiological studies problematic. In this paper, we present a fully
      automatic algorithm for the discrimination of the ventricular (VE) and SVE
      ectopic beats from the normal QRS complexes suited for a reliable HRV analysis.
      The QRS identification is based on the template matching method. The ectopic
      beats are identified based on several morphological and timing properties of the
      electrocardiogram (ECG) signal. The method incorporates several approaches and
      makes HRV analysis of large numbers of electrocardiograms feasible. It uses the
      template matching for the basic morphology check of the QRS complex and the P
      wave, the timing information to avoid unnecessary ectopic beat checks and to
      adjust thresholds and it also looks for a special QRS morphology, which is common
      in VEs. We used a testing set of 69 electrocardiograms selected from a large
      number of recordings. The selected ECGs contained abnormalities including ectopic
      beats, right branch bundle block, respiratory arrhythmia, blocked atrial
      extrasystole, high amplitude and wide T-waves. The evaluation of our method
      showed a specificity of 0.99, supraventricular ectopic beat sensitivity of 0.99
      and ventricular ectopic beat sensitivity of 0.98.

PMID- 10960746
TI  - Quantification and characterisation of arteries in retinal images.
AB  - A computerised system is presented for the automatic quantification of blood
      vessel topography in retinal images. This system utilises digital image
      processing techniques to provide more reliable and comprehensive information for
      the retinal vascular network. It applies strategies and algorithms for measuring
      vascular trees and includes methods for locating the centre of a bifurcation,
      detecting vessel branches, estimating vessel diameter, and calculating angular
      geometry at a bifurcation. The performance of the system is studied by comparison
      with manual measurements and by comparing measurements between red-free images
      and fluorescein images. In general an acceptable degree of accuracy and precision
      was seen for all measurements, although the system had difficulty dealing with
      very noisy images and small or especially tortuous blood vessels.

PMID- 10960747
TI  - ECG variable cine: computer program for presentation of temporal changes in ECG
      variables over different number of ECG leads.
AB  - The analysis of exercise electrocardiogram (ECG) is based on the alteration of
      the measured variables in the detection of coronary artery disease (CAD). In its
      existing form the analysis of the exercise ECG is laborious and requires much
      time. The temporal analysis of the ECG variable and the comparison between
      different phases of the exercise test is difficult and time consuming, especially
      the simultaneous examination of the variables over several leads. In this article
      we present a computer program, ECG Variable Cine, for the visualization of the
      temporal changes of values of exercise ECG variables over the selected ECG lead
      system. The program includes the stationary 3-D presentation for the variables'
      alteration simultaneously in all selected leads over the time of exercise test.
      In addition, the program determines two parameters; the average value of the
      variable over the selected leads at every sample moment, and the chronotropic
      index, a parameter that indicates heart rate response to exercise. According to
      the results the average value of ST-segment deviation at the end of the exercise
      over the leads and chronotropic index are clinically more competent than the
      maximum value of ST-segment depression in the detection of CAD.

PMID- 10960748
TI  - Decision analysis in dentistry--the last 30 years.
AB  - OBJECTIVES: To review publications in dentistry of decision analyses during the
      last 30 years. METHODS: A systematic review of the English literature from 1969
      to 1998 was performed using specified indexing terms. The number of retrieved
      articles in dentistry was compared with the number of articles in medicine. The
      quality of articles in dentistry presenting a decision tree with utilities and a
      sensitivity analysis was judged using a published peer review process. We report
      weaknesses of the analyses together with selected applications. RESULTS: Sixty
      seven articles were published on decision analysis in dentistry. Whilst the
      number of articles published in medicine has accelerated there has been a decline
      in the last four years in dental publications. Only 22 of the articles in
      dentistry presented a decision analysis with utilities and a sensitivity
      analysis. CONCLUSIONS: Current weaknesses of the decision analyses reported were:
      opaque basic assumptions in the description of the analysis, lack of data on
      patient preferences and of reliable data on the chances of the long-term effects
      and side effects of intervention together with an absence of sensitivity
      analyses. The decision analysis approach complements that of "evidence-based
      health care" by enabling the best empirical evidence to be used in clinical
      practice. Formal methods such as decision analysis will promote the rational use
      of existing knowledge. For it to do this the quality of research data will have
      to improve in dentistry. Furthermore decision analysis is important in education
      to demonstrate explicitly how decisions might be arrived at and improved.

PMID- 10960749
TI  - Clinical crown length changes from age 12-19 years: a longitudinal study.
AB  - OBJECTIVE: The objective of this study was to investigate the relationship
      between age, gender and clinical crown length using a longitudinal study design.
      METHOD: Four hundred and fifty-six sets of study models initially obtained for a
      large prospective longitudinal cohort study of orthodontic needs were examined.
      Each set of models corresponded to subjects at three different ages: 11-12, 14-15
      and 18-19years old. The clinical crown height of the maxillary right central
      incisor (11), maxillary right canine (13), maxillary left lateral incisor (22)
      and mandibular left central incisor (31) was measured from gingival crest to the
      incisal edge using digital calipers. RESULTS: Analysis revealed a significant
      (p<0.0001) age effect on crown length for all four teeth investigated. A
      significant gender effect was found in relation to the maxillary right canine,
      maxillary right central incisor and maxillary left lateral incisor. Pairwise
      comparisons of the means for each age group for the maxillary right canine,
      maxillary right central incisor and maxillary left lateral incisor revealed
      significant (p<0. 0001) increases in clinical crown length between each
      assessment period. CONCLUSION: The findings of the present study indicate that,
      the process of passive eruption, resulting in increased clinical crown length
      appears to continue throughout the teenage years. This finding is considered to
      be of importance to the clinician making treatment decisions for teenagers and
      young adults requiring treatment in the anterior segments of the mouth.

PMID- 10960750
TI  - Splints and stress transmission to teeth: an in vitro experiment.
AB  - OBJECTIVE: To determine the influence of hard and soft splints with two
      thicknesses on the stress transmission to the tooth supporting the splint and the
      opposite tooth. METHODS: Continuous vertical forces up to 500N were applied to
      two opposite first molar phantom teeth using a universal loading machine.
      Deformation was detected by strain gauges attached to the cervical area of the
      buccal and lingual aspects of the lower tooth. Strain, as a function of force,
      was collected and the slope, defined as the compliance (in microS/N) of the
      system, was calculated. RESULTS: The highest compliance was found with hard
      splints. When splints were constructed on the upper molar, the highest
      compressive compliance was registered on the buccal side (2.8 microS/N) and
      tension compliance on the lingual side (-0.35 microS/N). When constructed on the
      lower tooth, the opposite was found. Soft splints resulted in compression on both
      the buccal and lingual sides when adjusted to the upper or lower tooth. A higher
      compliance was found on the buccal side (1.26 microS/N), while on the lingual
      side, the values varied (0.48-0.78 microS/N). CONCLUSIONS: Soft splints are more
      efficient in protecting teeth against the damage of bending forces although there
      is an increase of compression forces. The tooth opposing a hard splint is exposed
      to a higher risk of bending forces.

PMID- 10960751
TI  - Penetration of radiocalcium at the margins of resin and glass ionomer dentine
      bonding agents in primary and permanent teeth.
AB  - OBJECTIVES: The purpose of this study was to compare the leakage of three resin
      dentine bonding agents (Prime and Bond, Scotchbond Multi-Purpose, Probond) and a
      glass ionomer dentine bonding agent (GC Fujibond LC), in cervical cavities
      prepared in primary and permanent molar teeth restored with a hybrid composite
      resin (Tetric). METHODS: Cervical cavities without a bevel at the cavo-surface
      margins were prepared in the buccal and lingual surfaces of extracted primary and
      permanent molar teeth. After being restored, the teeth were stored for 1 week in
      a saline solution at 37 degrees C and then thermally cycled between 5 and 55
      degrees C. Marginal leakage was determined subsequently using a radioactive
      isotope containing 45Ca and an autoradiographic technique. RESULTS: The results
      revealed that there were no statistically significant differences in microleakage
      of the bond between permanent and primary teeth dentine and Fuji Bond LC and
      Probond dentine bonding agents. The difference between permanent and primary
      teeth groups for gingival values of the Prime and Bond 2.1 group U=22.5, p=0.0355
      and the Scotchbond Multipurpose group U=24.0, p=0.0406 were statistically
      significant. There were no significant differences between the occlusal and
      gingival microleakage values in either primary or permanent teeth with Prime and
      Bond 2.1, Fuji Bond LC and Probond except the difference at Scotchbond
      Multipurpose in primary teeth. For primary teeth gingival margins, none of the
      bonding systems were significantly different from the control group. CONCLUSIONS:
      These results indicate that although no statistically significant differences
      were found between test and control group values, the use of Fuji II LC in
      cervical cavities with cementum margins in primary teeth would provide the best
      resistance to microleakage among the test materials while the use of Scotchbond
      Multi-Purpose would provide the best resistance to microleakage in cervical
      cavities with cementum margins in permanent teeth.

PMID- 10960752
TI  - The effect of interface stiffness on dentin-composite interfacial fracture
      resistance.
AB  - OBJECTIVES: The dentin-composite interface should withstand stresses that develop
      initially during composite polymerization and later during clinical function. The
      elastic behavior of the dentin-composite interface, which could be represented by
      an interfacial stiffness parameter, is not completely understood. The purpose of
      this study was to measure the relative interfacial stiffness of dentin-composite
      interfaces formed using commercially available dentin bonding agents and to
      relate these relative interfacial stiffness results to previously reported
      interfacial fracture toughness (K(ICi)) values. METHODS: The miniature short-rod
      fracture toughness specimen geometry containing a dentin-composite interface was
      used for testing. Specimens were aged in distilled water at 37 degrees C for
      180days prior to tensile loading at an extension rate of 0.5mm/min. The relative
      interfacial stiffness was determined from the initial slope of the force
      displacement curve that was obtained from each fracture toughness test. ANOVA,
      Fishers LSD, and linear regression tests were used for statistical analyses
      (p<0.05). RESULTS: The relative interfacial stiffnesses ranged from 16 to 92N/mm.
      The groups containing dentin-composite interfaces with greater depths of surface
      dentin demineralization generally exhibited higher interfacial stiffness than
      those with less dentin demineralization. Bonding to "wet" dentin produced higher
      relative interfacial stiffness results than bonding to "dry" dentin. A
      significant positive linear relationship was found among the individual
      (p=0.0001,r(2)=0.58) and the mean (p=0.0004,r(2)=0.97) relative interfacial
      stiffness and K(ICi) results. CONCLUSIONS: The significant positive relationship
      between the relative interfacial stiffness and K(ICi) results suggest a benefit
      (increased interfacial fracture resistance) of a relatively stiff dentin
      composite interface.

PMID- 10960753
TI  - Marginal adaptation of a new compomer under different conditioning methods.
AB  - OBJECTIVES: This in vitro study evaluated the marginal adaptation of compomer
      restorations placed using three different conditioning protocols. MATERIALS AND
      METHODS: Thirty extracted caries-free molars with 3mm diameter cylindrical cavity
      preparations were divided randomly into three groups based upon the conditioning
      treatment used: (I) 36% phosphoric acid; (II) non-rinse conditioner (NRC,
      Dentsply DeTrey); and (III) no conditioning. Cavities were restored with Dyract
      AP using Prime&Bond NT (Dentsply DeTrey) as an adhesive. Silicone impressions of
      the briefly etched enamel surfaces were taken after finishing the restorations.
      Each sample was then longitudinally sectioned and impressions were taken. Epoxy
      resin replicas were prepared for SEM analysis. Qualitative and quantitative
      assessment were performed separately for the enamel- and dentine-restorative
      interface. RESULTS: Enamel fractures and open margins along the enamel
      restorative margin were observed in some specimens in each group. No
      statistically significant difference was found in the percentage of gaps/cohesive
      failures between specimens prepared using different conditioning methods. For the
      dentine-restorative interface, uniform hybrid layers and long resin tags were
      often observed in Groups I and II. The hybrid layer in Group III was irregular
      and discontinuous along the interface. A significant difference (p<0.01) in the
      proportion of marginal gap was found between Group I (2%) and Group III (30%).
      CONCLUSIONS: Pre-treating the cavity with 36% phosphoric acid significantly
      improved the adaptation of the compomer and adhesive to dentine compared with no
      etching. The marginal quality at the enamel-compomer interface was not affected
      by the conditioning method used.

PMID- 10960754
TI  - Effect of hydrostatic pressure on regional bond strengths of compomers to
      dentine.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of hydrostatic
      pressure on the regional bond strengths of compomers to dentine. METHODS: Thirty
      freshly extracted molars were ground flat to expose the dentine and randomly
      divided into two groups for bonding: no hydrostatic pressure and hydrostatic
      pressure of 15cm H(2)O. Xeno CF, Dyract AP and F 2000 were applied to dentine
      surfaces pretreated by the respective bonding systems following the manufactures'
      instructions, and then restored with Clearfil AP-X. After 24h storage in water,
      the teeth were sectioned into 0.7-mm thick slabs and visually divided into three
      regional subgroups: the region communicating with the pulp through dentinal
      tubules (pulp horn); the region between the pulp horns (center); and the region
      between the pulp horn and DEJ (periphery). The specimens were trimmed to a cross
      sectional area of 1mm(2) and subjected to the micro-tensile bond test. The data
      were analyzed by one- and three-way ANOVA, and Fisher's PLSD (p<0.05). RESULTS:
      There were no significant regional differences of bond strengths for all the
      compomers tested (p>0.05). However, hydrostatic pressure significantly decreased
      the bond strength of F 2000 to all regions (p<0.05), while the bond strength of
      Dyract AP significantly decreased only at the pulp horn region (p<0.05). On the
      other hand, the bond strengths of Xeno CF seemed not to be affected by
      hydrostatic pressure (p>0.05). For Dyract AP and F 2000, the fracture modes were
      affected by hydrostatic pressure, while, for Xeno CF, there were no significant
      differences between the fracture modes with non- or positive hydrostatic
      pressure. SIGNIFICANCE: Simulated pulpal pressure of 15cm H(2)O had a greater
      influence on the bond strengths of compomers to dentine than did dentine regions.
      Therefore, when measuring the bond strengths of compomers to dentine under the
      simulated in vivo conditions, the wetness of the dentine surface, as well as the
      intrinsic properties of each material should be seriously considered.

PMID- 10960755
TI  - Flexural properties of fiber reinforced composite using a vacuum/pressure or a
      manual adaptation manufacturing process.
AB  - PURPOSE: This study investigated the influence of fiber content and water storage
      on the flexural strength of beams made of two fiber-reinforced composites (FRC),
      the Vectris and the FibreKor system. MATERIAL AND METHODS: A manual adaptation
      method (FibreKor, n=30) and a vacuum/pressure process (Vectris, n=30) were
      compared using 25x4x2mm(3) beams. One group of the Vectris (n=10) and the
      FibreKor beams (n=10) was stored in water for 24h, a further group was thermal
      cycled (TC) 6000x5 degrees C/55 degrees C, and a third group was stored in water
      for 30days at 37 degrees C. All beams were then loaded to failure using a three
      point bending test and the flexural strength was calculated. Finally, the fiber
      volume percent (vol%) was determined. RESULTS: Generally, the flexural strength
      decreased significantly with increasing storage time independent of the
      investigated fiber- and/or manufacturing system. With the parameters
      24h/TC/30days, the mean of flexural strength for the Vectris beams was
      618/579/545N/mm(2), and for FibreKor 585/534/499N/mm(2). A fiber content of
      28.1+/-0.4vol% was assessed for the Vectris beams and 12.8+/-0.6vol% for the
      FibreKor beams. After 24h storage in water, the Vectris and the FibreKor beams
      demonstrated a statistically significant higher flexural strength than after
      30days storage in water. CONCLUSIONS: A vacuum/pressure manufacturing process in
      contrast to manual adaptation, resulted in a markedly higher fiber content, but
      did not necessarily lead to significantly higher flexural strength. Not only the
      fiber content, but also matrix composition as well as the bond between fibers and
      matrix determined the properties of FRC.

PMID- 10960756
TI  - An ultrastructural study of the application of dentine adhesives to acid
      conditioned sclerotic dentine.
AB  - OBJECTIVE: This in vitro study examined the ultrastructure of resin-infiltrated
      sclerotic dentine following the application of a self-etching primer, with or
      without the adjunctive use of phosphoric acid pre-conditioning. MATERIALS AND
      METHODS: Non-carious, natural cervical sclerotic lesions were hand-cleaned with a
      slurry of pumice and chlorhexidine and bonded without further cavity preparation.
      One group was bonded using Clearfil Liner Bond 2V (Kuraray Co. Ltd, Osaka, Japan)
      alone. Specimens from the other group were pre-conditioned with K-etchant (40%
      phosphoric acid gel, Kuraray) prior to the application of the same self-etching
      primer. Artificially prepared wedge-shaped lesions were also made in sound
      bicuspids, bonded using the two methods, and used as controls for the two groups.
      For SEM examination, each specimen was cryofractured into two halves through a
      pre-formed slit made on the lingual surface, after the respective conditioning
      treatment. Different locations within the lesions were examined after rinsing of
      the phosphoric acid/self-etching primer and specimen dehydration. For TEM
      investigation, specimens were bonded with the adhesive. Both demineralised and
      undemineralised ultrathin sections were prepared from the occlusal, gingival and
      deepest part of the wedge-shaped bonded lesions following specimen fixation,
      dehydration and resin embedding. RESULTS: A hypermineralised surface layer was
      present on the surface of etched sclerotic dentine. This layer was thicker in the
      deepest part of the natural lesions, where bacterial colonisation of the lesion
      surface was also apparent. Both treatment protocols were unable to effectively
      dissolve sclerotic casts that occluded the dentinal tubules. Depending upon the
      thickness of the surface layers at different locations in the natural lesion,
      self-etching primer treatment alone resulted in reduction of the thickness of the
      authentic hybrid layer (i.e. hybridised intertubular dentine). This was also true
      of phosphoric acid pre-conditioning along the deepest part of the natural
      lesions. Within this region, intertubular dentine completely devoid of an
      authentic hybrid layer could be seen in both treatment groups. Resin tags were
      also sparsely observed in such regions. CONCLUSIONS: Adhesive strategies that
      rely mostly on micromechanical retention alone may be compromised by the sporadic
      absence of the hybrid layer and resin tags in sclerotic dentine. Based on the
      ultrastructural features presented, it is further speculated that adaptive
      strategies such as removal of the surface layers and extended etching time may
      not be completely effective in improving bonding efficacy in highly sclerotic
      dentine. Interdisciplinary research should be continued to develop alternative
      procedures for bonding resins equally well to sound and sclerotic dentine.

PMID- 10960758
TI  - Erratum to "Adaptation of dental plaque to metabolise maltitol with other
      sweeteners".

PMID- 10960757
TI  - Structural reliability of alumina-, feldspar-, leucite-, mica- and zirconia-based
      ceramics.
AB  - OBJECTIVES: The objective of this study was to test the hypothesis that
      industrially manufactured ceramic materials, such as Cerec Mark II and Zirconia
      TZP, have a smaller range of fracture strength variation and therefore greater
      structural reliability than laboratory-processed dental ceramic materials.
      METHODS: Thirty bar specimens per material were prepared and tested. The four
      point bend test was used to determine the flexure strength of all ceramic
      materials. The fracture stress values were analyzed by Weibull analysis to
      determine the Weibull modulus values (m) and the 1 and 5% probabilities of
      failure. RESULTS: The mean strength and standard deviation values for these
      ceramics are as follows: (MPa+/-SD) were: Cerec Mark II, 86.3+/-4.3; Dicor,
      70.3+/-12.2; In-Ceram Alumina, 429. 3+/-87.2; IPS Empress, 83.9+/-11.3; Vitadur
      Alpha Core, 131.0+/-9.5; Vitadur Alpha Dentin, 60.7+/-6.8; Vita VMK 68, 82.7+/
      10.0; and Zirconia-TZP, 913.0+/-50.2. There was no statistically significant
      difference among the flexure strength of Cerec Mark II, Dicor, IPS Empress,
      Vitadur Alpha Dentin, and Vita VMK 68 ceramics (p>0.05). The highest Weibull
      moduli were associated with Cerec Mark II and Zirconia-TZP ceramics (23.6 and
      18.4). Dicor glass-ceramic and In-Ceram Alumina had the lowest m values (5.5 and
      5.7), whereas intermediate values were observed for IPS-Empress, Vita VMK 68,
      Vitadur Alpha Dentin and Vitadur Alpha Core ceramics (8.6, 8.9, 10.0 and 13.0,
      respectively). CONCLUSIONS: Except for In-Ceram Alumina, Vitadur Alpha and
      Zirconia-TZP core ceramics, most of the investigated ceramic materials fabricated
      under the condition of a dental laboratory were not stronger or more structurally
      reliable than Vita VMK 68 veneering porcelain. Only Cerec Mark II and Zirconia
      TZP specimens, which were prepared from an industrially optimized ceramic
      material, exhibited m values greater than 18. Hence, we conclude that
      industrially prepared ceramics are more structurally reliable materials for
      dental applications although CAD-CAM procedures may induce surface and subsurface
      flaws that may adversely affect this property.

PMID- 10960759
TI  - Possible correlation between urinary muramidase (E.C.3.2.1.27) and oesophageal
      cancer.
AB  - The diagnostic value of determination of low-mass enzymes in urine is very
      important, especially for early detection of some diseases. There are several
      investigations about lysozyme (muramidase, E.C.3.2. 1.27) and its correlation
      with some malignancies, but until now nothing has been reported about the
      lysozyme, and oesophageal cancer. This study was undertaken for determination of
      lysozyme concentration in urine of 32 oesophageal cancer patients to evaluate if
      this enzyme activity changes in oesophageal cancer used for detection of this
      cancer especially in its early stage. We used high performance liquid
      chromatography (HPLC) for determination of urinary muramidase after Sep-pac pre
      purification of the samples. The mean results of lysozymuria in patients in
      comparison with the mean of enzyme activity in normal controls were statistically
      high (12.14+/-0.403 vs. 2.04+/-0.134, P</=0.001) Our finding also indicated that
      the severity of lysozymuria in these patients is stage dependent.

PMID- 10960760
TI  - Improvement of idarubicin induced antitumor activity and bone marrow suppression
      by theanine, a component of tea.
AB  - We have examined the effect of theanine, a specific amino acid in green tea, on
      idarubicin (IDA)-induced antitumor activity and toxicity. In combination with
      theanine, IDA (0.25 mg/kg per day x4 days, a dose that does not show antitumor
      activity) had significant antitumor activity in P388-bearing mice. The IDA
      concentration in the tumors in the theanine plus IDA group increased to twice the
      level in the IDA alone group. Furthermore, the decrease in tumor weight caused by
      IDA at 1.0 mg/kg per day x4 days (at this dose IDA exhibits antitumor activity)
      was significantly amplified by theanine. The numbers of leukocyte and bone marrow
      cells decreased significantly on IDA injection. Theanine significantly reversed
      these changes. These results suggest that theanine selectively moderates the IDA
      induced toxicities. Until recently, the antitumor activity and related toxicities
      of this chemotherapeutic agent in leukemia could not be distinguished. Theanine
      increases the IDA-induced antitumor activity and ameliorates the toxicities.

PMID- 10960761
TI  - Mitomycin C induces apoptosis in a caspases-dependent and Fas/CD95-independent
      manner in human gastric adenocarcinoma cells.
AB  - We investigated the mechanism of mitomycin C (MMC)-induced apoptosis in SNU-16
      human gastric adenocarcinoma cells. Caspase-8 and caspase-3 were activated in MMC
      treated cells whereas caspase-1 was not activated, and cytochrome c was released
      from mitochondrial membrane to cytosol suggesting that caspase-9 was activated
      during the MMC-induced apoptotic process. Protein kinase C (PKC) delta was
      cleaved to its characteristic 40 kDa fragment in a caspase-3-dependent manner; on
      the other hand PKC zeta was cleaved to approximately 40 kDa independently of
      caspase-3 in the drug-induced apoptosis of the cells. Incubation with z-DEVD-fmk
      and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk) almost
      completely abrogated MMC-induced DNA fragmentation, indicating that activation of
      these caspases was crucially involved in MMC-induced apoptosis. Activation of
      caspase-8 in response to Fas triggering by recruitment of caspase-8 to the Fas
      has also been found, however, MMC did not induce FasL and Fas expression, as
      evidenced by reverse transcriptase-polymerase chain reaction and Western
      blotting. Taken together, these findings indicate that MMC-induced apoptosis in
      SNU-16 cells was mediated by caspase-8, caspase-9, and caspase-3 activation
      independently of FasL/Fas interactions.

PMID- 10960762
TI  - Preventive effects of danazol on endometrial carcinogenesis in mice.
AB  - Short and long-term experiments were designed to determine effects of danazol on
      estrogen-related endometrial carcinogenesis in mice. The short-term assays showed
      that danazol decreased expression levels of c-fos/jun mRNA and their oncoproteins
      induced by estradiol-17beta (E2). For the long-term assay, 85 female ICR mice
      were given N-methyl-N-nitrsourea solution into their uterine corpora. The animals
      were divided into three groups as follows: Group 1, E2-diet (5 ppm) plus danazol
      (2 mg/body (s.c.), every 4 weeks); Group 2, E2-diet alone, Group 3, basal diet
      alone. At 30 weeks, incidences of atypical and complex endometrial hyperplasia
      were significantly decreased by danazol-treatment. These results suggest that
      danazol has preventive effects on estrogen-related endometrial carcinogenesis in
      mice, through the suppression of estrogen-induced c-fos/jun-expression.

PMID- 10960763
TI  - Mutation analysis of mitotic checkpoint genes (hBUB1 and hBUBR1) and
      microsatellite instability in adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a neoplasm of T-lymphocytes, and human T
      cell lymphotropic virus type-I (HTLV-I) is etiologically considered as the
      causative virus of ATLL. The karyotypes of ATLL are very complex in both number
      and structure, although no specific karyotype abnormalities have been identified.
      HTLV-I is thought to integrate its provirus into random sites in host chromosomal
      DNA and induces chromosomal instability. The BUB gene is a component of the
      mitotic checkpoint in budding yeast. Recently, human homologues of the BUB were
      identified and mutant alleles of hBUB1 and hBUBR1 were detected in two colorectal
      tumor cell lines, which showed microsatellite instability (MIN). In vitro, BUB
      proteins form a complex of monomers. These proteins interact with the human MAD1
      gene product, a target of the HTLV-1 tax oncogene. We examined the role of
      checkpoint gene in the chromosomal abnormalities of ATLL by investigating
      mutations of hBUB1 and hBUBR1, and MIN of replication errors of BAX, insulin-like
      growth factor, and transforming growth factor beta type II. We analyzed ten cases
      with ATLL and eight B-cell lymphomas (five diffuse large cell lymphomas, three
      follicular lymphomas). Complex chromosomal abnormalities were detected in ATLL,
      while B-cell lymphomas showed only simple or minimal chromosomal abnormalities.
      Significant mutations/deletion of hBUB1 or hBUBR1 were detected in four of ten
      cases with ATLL, including two heterozygous point mutations, one homozygous point
      mutation, and one with a 47 bp deletion. In contrast, only one of eight B-cell
      lymphomas showed nonsense mutation of hBUBR1. None of the ATLL and B-cell
      lymphomas showed MIN. In the multistage process of leukemogenesis of ATLL, our
      findings indicate that mutations of mitotic checkpoint genes may play an
      important role in the induction of complex chromosomal abnormalities.

PMID- 10960764
TI  - Cytotoxity of non-alkaloidal taxane diterpenes from Taxus chinensis against a
      paclitaxel-resistant cell line.
AB  - Seven taxane diterpenes were isolated from the EtOH extract of the aerial parts
      of Taxus chinensis, and evaluated for cytotoxicity against nine human cell lines,
      including a beta-tublin mutant resistant to paclitaxel. Compound 2, a non
      alkaloid-type taxane diterpene, showed significant cytotoxicity in most cell
      lines, and notably, equipotent against both parental and beta-tublin mutant tumor
      cell lines.

PMID- 10960765
TI  - Photosensitization induced reactive oxygen species and oxidative damage in human
      erythrocytes.
AB  - Generation of reactive oxygen species by photosensitization is the corner stone
      of photodynamic therapy of tumors. Cell damage may be mediated by free radical
      species and lipid peroxidation of their membranes. The effects of oxygen active
      species (.OH and O(2)(.-) radicals) photogenerated by the novel photosensitizer m
      chloroperbenzoic acid (m-CPBA) on human erythrocyte integrity and stability were
      studied. The biological toxicity of the reactive oxygen species on human red
      blood cells (RBCs) was evident by increased osmotic fragility, spherocytosis and
      haemolysis. The haemolysis was increased in concentration and time dependent
      manner. The lipid peroxidation product thiobarbituric acid reactive substances
      (TBARS) was elevated in m-CPBA photosensitized RBCs indicating increased
      oxidative stress. This was accompanied with a depletion of erythrocyte
      glutathione (GSH). These effects were blunted by hydroxyl radical scavengers,
      thiourea and mannitol, which might indicate the production of (.)OH radical by
      photosensitization with m-CPBA. The antioxidant enzyme activities such as
      superoxide dismutase (SOD), catalase (CAT), peroxidase (Px) and glutathione
      peroxidase (GSH-Px) were elevated in RBCs treated with m-CPBA in the presence and
      absence of hydroxyl radical scavengers, mannitol and thiourea. These results
      suggested that the main oxygen radical photogenerated from m-CPBA is O(2)(&z.rad;
      ) radical, which is transformed to (.)OH radical probably by hydrogen
      abstraction. This is probably the main damaging oxygen species and played an
      essential role in oxidative haemolysis mediated by peroxidation of membrane
      lipids of human erythrocytes. This study provides an investigational promising
      data for photodynamic therapy.

PMID- 10960767
TI  - Detection of mammaglobin expressing cells in blood of breast cancer patients.
AB  - Expression of human mammaglobin (hMAM) was published to be exclusively expressed
      in mammary tissue, in solid tumors, axillary lymph nodes and disseminated cancer
      cells in blood of breast cancer patients. A quantitative real-time reverse
      transcription-polymerase chain reaction (RT-PCR) test was applied to investigate
      hMAM expression in blood of breast cancer patients. Mammaglobin mRNA expression
      was found not only in breast cancer cell lines but also in cell lines of other
      cancer origin. In our patient cohort hMAM expression in 11/98 (11%) samples of
      breast cancer and 3/12 (25%) ovarian cancer patients could be detected. hMAM mRNA
      expression as a candidate marker for the detection of disseminated cancer cells
      in blood of breast cancer patients showed low sensitivity and reduced tissue
      specificity. A prognostic significance of hMAM expression could not be
      demonstrated.

PMID- 10960766
TI  - An improved rapid procedure for fluorescence in situ hybridization that is
      applicable to intraoperative cancer cytodiagnosis.
AB  - Fluorescence in situ hybridization (FISH) is among the most simple and useful
      methods for detecting numerical and structural aberration of chromosomes but it
      requires 12-24 h to complete. We devised a rapid FISH method that can be
      performed within 2 h. Here we describe the technique, which we have found to be
      extreme simple and as sensitive and specific as standard FISH, making it highly
      suitable for clinical use.

PMID- 10960768
TI  - Correlation of telomere lengths in normal and cancers tissue in the large bowel.
AB  - The hypothesis that telomeres in colorectal cancer cells exhibit age-related
      shortening, as in normal cells of the colorectal epithelium, was tested with
      samples of non-cancerous mucosa and cancer tissue from 124 patients (aged 29-97
      years). Shortening with aging could be demonstrated for both normal and cancer
      tissues; regression analysis showed rates for length reduction of 44 and 50 base
      pair/year, respectively. Straight, essentially parallel, lines were obtained for
      the two cases, normal tissue values being about 2 kilobase pairs (kbp) higher,
      with a significant correlation between data at the individual patient level.

PMID- 10960769
TI  - Hypomethylation and overexpression of c-jun and c-myc protooncogenes and
      increased DNA methyltransferase activity in dichloroacetic and trichloroacetic
      acid-promoted mouse liver tumors.
AB  - Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver
      carcinogens. Methylation of the c-jun and c-myc genes, expression of both genes
      and DNA methyltransferase (DNA MTase) activity were determined in liver tumors
      initiated by N-methyl-N-nitrosourea and promoted by DCA and TCA in female B6C3F1
      mice. Hypomethylated and over-expression of c-jun and c-myc genes were found in
      DCA- and TCA-promoted liver tumors. DNA MTase activity was increased in tumors
      while decreased in non-involved liver. Thus, DCA- and TCA-promoted carcinogenesis
      appears to include decreased methylation and increased expression of c-jun and c
      myc genes in the presence of increased DNA MTase activity.

PMID- 10960770
TI  - Enhancing effects of Thai edible plants on 2-amino-3, 8-dimethylimidazo(4,5
      f)quinoxaline-hepatocarcinogenesis in a rat medium-term bioassay.
AB  - Boesenbergia pandurata (Zingiberaceae), Languas galanga (Zingiberaceae) and
      Citrus hystrix (Rutaceae) are edible plants that are commonly used as flavors or
      condiments in various Thai food dishes. They are known to exert strong anti
      promoting activity in a test of tumor promoter-induced Epstein-Barr virus (EBV)
      activation. In the present study their effects on hepatocarcinogenesis were
      investigated in a medium-term bioassay using F344 male rats. C. hystrix
      significantly enhanced 2-amino-3,8-dimethylimidazo(4, 5-f)quinoxaline-associated
      preneoplastic liver cell focus development while B. pandurata and L. galanga had
      borderline effects. The results suggest that C. hystrix as well as B. pandurata
      and L. galanga may contain agents augmenting the hepatocarcinogenicity of 2-amino
      3,8-dimethylimidazo(4,5-f)quinoxaline.

PMID- 10960771
TI  - Transfer of p14ARF gene in drug-resistant human breast cancer MCF-7/Adr cells
      inhibits proliferation and reduces doxorubicin resistance.
AB  - The INK4a/ARF locus on human chromosome 9p21 encodes two tumor suppressors,
      p16INK4a and p14ARF, that restrain cell growth by affecting the functions of the
      retinoblastoma protein and p53, respectively. Overexpression of ARF results in
      cell cycle arrest in both G1 and G2. To elucidate the effect of p14ARF gene on
      multidrug-resistant tumor cells, we transferred a p14ARF cDNA into p53-mutated
      MCF-7/Adr human breast cancer cells. In this report we demonstrated for the first
      time that p14ARF expression was able to greatly inhibit the MCF-7/Adr cell
      proliferation. Furthermore, p14ARF expression resulted in decrease of MDR-1 mRNA
      and P-glycoprotein production, which linked to the reducing resistance of MCF
      7/Adr cells to doxorubicin. These results imply that drug resistance might be
      effectively reversed by the wild-type p14ARF expression in human breast cancer
      cells.

PMID- 10960772
TI  - Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by
      chemotherapy.
AB  - The p53 gene is associated with G1 arrest during the cell cycle and with
      apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal
      squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI)
      and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty
      patients with esophageal carcinoma who had received chemotherapy prior to surgery
      were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ
      end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining
      with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression,
      respectively. The histological response rate of chemotherapy was 20.0%. A
      significant correlation between p53-negative expression and response to
      chemotherapy was found (P<0. 01). The AIs and Ki-67LIs in p53-negative tumors
      with ineffective responses to chemotherapy were significantly higher than those
      in p53-positive tumors with ineffective responses (P<0.05). The AIs and Ki-67LIs
      were significantly lower in p53-negative tumors with effective responses to
      chemotherapy than those in p53-negative tumors with ineffective responses (P<0.05
      and P<0.01, respectively). Furthermore, significant correlations were found
      between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P<0.05). In esophageal
      carcinoma, p53-negative tumors with highly proliferative cells might be
      susceptible to apoptosis induced by chemotherapy.

PMID- 10960773
TI  - One-allele system in the Korean for MboI-RFLP in exon 1 of the human tyrosinase
      (TYR) gene.
AB  - Oculocutaneous albinism is an autosomal recessive genetic disorder. Several types
      of oculocutaneous albinism are caused by mutation in related genes.
      Oculocutaneous albinism 1 is associated with the tyrosinase gene. The human
      tyrosinase gene (TYR) encodes tyrosinase, a key enzyme in melanin biosynthesis.
      As exon 1 of the gene shows an MboI-RFLP within codon 192 in Caucasians, we
      studied allele frequencies of MboI 192 polymorphism in 200 chromosomes from 100
      unrelated normal Korean individuals. As a result, only one allele system, the
      presence of the MboI 192 site, was detected in the Korean.

PMID- 10960774
TI  - Stem cell factor and IL-6 do not promote complete maturation of human cultured
      mast cells from umbilical cord blood cells: an ultrastructural study.
AB  - Human mast cells are classified into two phenotypes based on their neutral
      protease compositions. One type is a tryptase-positive and chymase-positive MCTC
      cell that is predominant in the skin, another is a tryptase-positive and chymase
      negative MCT cell that is predominant in the lung. Cord blood-derived human mast
      cells cultured in the presence of stem cell factor and interleukin-6 are a
      mixture of MCTC and MCT at various ratios, as revealed by immunocytochemical
      staining. We performed an electron microscopic analysis of cord blood-derived
      human cultured mast cells and found that they were so immature that we could not
      distinguish MCT and MCTC from their ultrastructural morphology. The response to
      secretagogues was not the response of MCTC but rather of MCT. Although human
      cultured mast cells are the most useful cells for use in in vitro experiments,
      the present culture condition supplemented with stem cell factor and interleukin
      6 does not develop fully mature mast cells in vitro.

PMID- 10960775
TI  - Human stratified squamous epithelia differ in cellular fatty acid composition.
AB  - The phospholipid component of the cellular membrane is crucial to the structure
      and function of cells. Basal cells from three epithelial tissues, adult human
      skin epidermis, oral mucosa, and hair follicles, grow rapidly in serum- and lipid
      free medium. Analysis of phospholipid extracts from the above three types of
      stratified squamous epithelium in both in vivo and in vitro was done to relate
      fatty acid cell composition to cell function. The fatty acid composition of hair
      follicles in vivo was analyzed in plucked scalp hairs, and those of skin
      epidermis and oral mucosa in vivo were analyzed after separating the tissue into
      suprabasal and basal layers. The fatty acid composition of the in vivo cells from
      hair follicles shows a partial essential fatty acid (EFA)-deficient state. There
      was no significant difference between the skin epidermis and the oral mucosa in
      the fatty acid composition of the in vivo cells from each basal layer. However,
      in the suprabasal layers, the percent of linoleic acid (18:2) from the skin
      epidermis was higher than that from the oral mucosa. This study shows that total
      fatty acid composition in cell membranes of stratified squamous epithelium varies
      with their keratinization pattern. When cultured, the three types of rapidly
      growing keratinocytes showed the same essential fatty acid deficient pattern in
      the membrane phospholipids.

PMID- 10960776
TI  - Haptoglobin is a natural regulator of Langerhans cell function in the skin.
AB  - Langerhans cells (LC), the best-understood antigen presenting cells (APC) of the
      skin, are functionally plastic. Freshly obtained LC readily activate allogeneic T
      cells, but are incapable of activating autologous, naive T cells. When placed in
      culture in the presence of GM-CSF, LC up-regulate surface expression of class I
      and II MHC molecules along with co-stimulatory molecules, such as B7, CD40 and IL
      12. This functional transformation enables the cells to activate naive,
      autologous T cells in vitro. It is paradoxical that intracutaneous administration
      of exogenous GM-CSF fails to induce intraepidermal LC to undergo functional
      transformation in situ. It has been reported that serum contains a factor that
      prevents fresh LC from undergoing functional transformation in culture, and the
      relevant serum factor has now been identified as haptoglobin (Hp), based on the
      following experimental results: (a) SDS-PAGE, amino acid sequencing, and mass
      spectrometric analyses of the inhibitory factor purified by high performance
      liquid chromatography (HPLC) from normal human serum revealed molecules
      completely homologous to Hp alpha-1 chain; (b) pure human Hp, but not serum
      depleted of Hp, inhibited fresh LC from acquiring the capacity to activate
      autologous T cells in vitro; (c) abundant Hp was detected in cytoplasmic
      compartments of fresh, but not cultured, LC. It was concluded that Hp, an acute
      phase protein, is a systemically-derived factor that prevents epidermal LC from
      spontaneously undergoing functional maturation in the skin. This novel property
      of Hp may be important in ameliorating or preventing certain T cell-dependent
      inflammatory skin diseases.

PMID- 10960777
TI  - The effect of herpesvirus infection on the expression of cell adhesion molecules
      on cultured human dermal microvascular endothelial cells.
AB  - Cell-mediated immune response to herpes simplex virus (HSV) may be important in
      the pathogenesis of herpes keratitis, erythema multiforme or Behcet's disease. We
      examined whether herpesvirus infection regulates the expression of cell adhesion
      molecules on cultured human dermal microvascular endothelial cells (HDMEC) and
      the regulation of T-lymphocytes binding to HDMEC. The expression of intercellular
      adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), or E
      selectin on HDMEC increased significantly after treatment with HSV-1, HSV-2, or
      measles virus on HDMEC. Anti-IL-1 alpha antibody or anti-TNF alpha antibody
      partially inhibited the expression of ICAM-1, VCAM-1, or E-selectin on HDMEC. The
      binding of T-lymphocytes to HDMEC increased significantly after the treatment of
      HSV-1 or measles virus on HDMEC. The binding of T-lymphocytes to HDMEC was
      significantly inhibited after 16 h of incubation following treatment with anti
      ICAM-1 antibody, anti-IL-1 alpha antibody or anti-TNF alpha antibody to HDMEC.
      These study results suggest that HSV induces the increased expression of ICAM-1,
      or induction of VCAM-1 and E-selectin on HDMEC and that among these adhesion
      molecules, the expression of ICAM-1 on HDMEC mainly regulates the binding of T
      lymphocytes to HDMEC. The data also suggest that IL-1 alpha or TNF alpha which
      was produced by HSV infected HDMEC may be related to these events.

PMID- 10960778
TI  - Suprathreshold doses of hapten are required to induce both contact
      hypersensitivity and tolerance.
AB  - Whereas both high (conventional) and low (optimal) doses of epicutaneously
      applied hapten induce contact hypersensitivity in normal mice, only conventional
      doses retain their capacity to induce contact hypersensitivity after acute, low
      dose ultraviolet B radiation in UVB-resistant mice. Recent evidence indicates
      that conventional doses of hapten as well as acute, low dose ultraviolet B
      radiation destroy virtually all epidermal Langerhans cells, which leads to the
      conclusions that (a) dermal antigen presenting cells have a prominent role to
      play in contact hypersensitivity induction, and that (b) Langerhans cell provide
      this function only in normal skin, and only if non-toxic amounts of hapten are
      present. We have now explored the ability of suprathreshold, threshold, and sub
      threshold doses of hapten to induce tolerance when painted on or injected into
      normal skin or skin exposed to ultraviolet B radiation. Our results indicate that
      a single exposure of low dose, ultraviolet B radiation generated tolerance
      promoting signals within the epidermis when a threshold dose of hapten was
      painted on the exposed site. By contrast, suprathreshold doses of hapten painted
      on skin after four consecutive daily doses of ultraviolet B radiation led to
      tolerance that arose exclusively from cells within the dermis. In absence of
      ultraviolet B radiation, epicutaneously applied hapten failed uniformly to induce
      tolerance, whether applied at suprathreshold, threshold or sub-threshold doses.
      We conclude that normal skin lacks cells with inherent tolerance-promoting
      capacity, but that cells of this type can emerge within either epidermis or
      dermis after exposure to acute, low dose ultraviolet B radiation.

PMID- 10960779
TI  - Mast cells in the cutaneous lesions of sarcoidosis: their subtypes and the
      relationship to systemic manifestations.
AB  - Possible involvement of mast cells in pulmonary sarcoidosis has been suggested,
      however whether mast cells are involved in cutaneous sarcoidosis remains unknown.
      We undertook a morphological study of mast cells in the lesional skin from 17
      patients with cutaneous sarcoidosis using immunohistochemical methods. Mast cells
      were present in non-parenchymal fibrous areas, but not in granulomatous areas, in
      the biopsy specimens from the cutaneous lesions. However, there were no
      significant differences between the number of mast cells in the lesional skin and
      that in non-lesional skin from the patients. Mast cells containing substantial
      quantities of both tryptase and chymase (MC(TC) cells) were present in 41% of the
      patients, and cells containing tryptase but not chymase (MC(T) cells) were
      present in 59% of patients. All patients of the former group showed systemic
      manifestations of the disease concomitantly. Serum angiotensin I-converting
      enzyme levels were elevated in 71.4% of the former group, and in 30% of the
      latter group. This study for the first time demonstrated that mast cells were
      present in non-parenchymal fibrous areas of the cutaneous lesions of sarcoidosis,
      and the mast cell subtypes may be related to systemic manifestations.

PMID- 10960780
TI  - The expression of nonchordate deuterostome Brachyury genes in the ascidian Ciona
      embryo can promote the differentiation of extra notochord cells.
AB  - The notochord is a structure present in all chordates and its development
      requires the transcription of Brachyury. While previous studies have shown that
      Brachyury is essential for notochord formation in vertebrate embryos, this gene
      is also expressed during the embryogenesis of nonchordate deuterostomes,
      hemichordates and echinoderms. Here we report that nonchordate deuterostome
      Brachyury genes can trigger the differentiation of extra notochord cells when
      these genes are ectopically expressed in ascidian embryos. The 2.6 kb upstream
      region of fork head gene (Ci-fkh) of Ciona intestinalis promotes the tissue
      specific expression of a reporter gene in endoderm, notochord and nerve cord. By
      taking advantage of this promoter, we misexpressed the Brachyury gene of ascidian
      (Ci-Bra), cephalochordate amphioxus (Am(Bb)Bra2), hemichordate acorn worm
      (PfBra), and echinoderm sea urchin (SpBra), in Ciona embryos. The misexpression
      of not only the chordate Brachyury, but also the nonchordate deuterostome
      Brachyury, resulted in the transformation of presumptive endodermal cells into
      notochord cells. This was confirmed by in situ hybridization experiments using
      four different notochord-specific probes from Ciona that have different temporal
      expression patterns. RT-PCR analyses indicated that Ci-Bra was not upregulated by
      the product of Am(Bb)Bra2, PfBra or SpBra. In situ hybridization showed no
      ectopic expression of Ci-Bra in the manipulated embryos. These results suggest
      that the introduction of nonchordate deuterostome Brachyury genes into ascidian
      embryos can trigger the differentiation of notochord cells in ascidian embryos.
      Evolutionary alteration in the genetic circuitry, especially downstream of this
      transcription factor, seems critical for the evolution of notochord and chordate
      body plan.

PMID- 10960781
TI  - Zebrafish mutations in Gli-mediated hedgehog signaling lead to lens
      transdifferentiation from the adenohypophysis anlage.
AB  - It is known that the earliest lens marker delta-crystallin is expressed
      abundantly in Rathke's pouch of the chicken, suggesting a close relationship
      between the cell states of the adenohypophysis (pituitary) anlage and the early
      lens. We show here that the zebrafish midline mutants you-too (yot) and iguana
      (igu) develop lenses from the adenohypophysis anlage. The early adenohypophysis
      anlage of normal zebrafish expresses lim3 and six3 but in yot(ty119) mutants the
      anterior part of the anlage lacks lim3 expression, and instead produces a
      crystallin-expressing cell population which develops into a large lens structure
      expressing beta and gamma-crystallins, but is not associated with retina tissues.
      Among the zebrafish mutants with midline defects, midline lenses were observed in
      two mutant alleles of yot and an allele of igu, but not in other mutants (syu,
      con, smh, dtr, uml, spi and lok). Two yot mutant alleles with midline lenses
      likely encode dominant negative forms of the Gli2 protein which will interfere
      with transcriptional activation by other Gli proteins. The observation argues
      that overall inhibition of Shh-Gli signaling leads the adenohypophysis anlage to
      transdifferentiate into lens.

PMID- 10960782
TI  - Fibroblast growth factor signaling is required for the proliferation and
      patterning of progenitor cells in the developing anterior pituitary.
AB  - The proliferation and patterning of progenitor cells in the anterior pituitary
      require signals derived from the neuroepithelium of the juxtaposed infundibulum.
      The infundibulum expresses Fibroblast growth factor (Fgf) 8 and Fgf 18, and FGFs
      can mimic some of the activities of the infundibulum. The requirement for FGF
      signaling during growth and patterning of the anterior pituitary has not,
      however, been established. By blocking FGF receptor signaling in explants of the
      anterior pituitary cultured in vitro we provide evidence that FGF signaling
      derived from the infundibulum is required for the proliferation and patterning of
      progenitor cells in the anterior pituitary.

PMID- 10960783
TI  - A direct screen for secreted proteins in Xenopus embryos identifies distinct
      activities for the Wnt antagonists Crescent and Frzb-1.
AB  - To determine the spectrum of secreted proteins that are present in the
      extracellular space of early Xenopus embryos, a direct secretion screen was
      performed. Surprisingly, 24% of previously identified bona fide secretory
      proteins corresponded to four secreted Wnt antagonists of the same family: frzb
      1, sizzled, sfrp-2 and crescent. sfrp-2 and crescent are novel components of the
      growing cocktail of growth factor antagonists secreted by Spemann organizer cells
      in Xenopus. Crescent is first expressed at blastula, defining a deep endodermal
      region that may be homologous to the avian hypoblast. Unlike other members of
      this family of inhibitors, microinjection of crescent mRNA causes the development
      of cyclopic embryos, even though the amount of anterior neural tissue is normal.
      In crescent-injected embryos, studies with specific markers indicate that
      morphogenetic movements of the anterior midline are abnormal, resulting in a more
      posterior location of prechordal plate and ventral forebrain markers with respect
      to the developing eye field. The results are discussed in light of recent
      findings in zebrafish and Xenopus that suggest that Wnt signaling through non
      canonical (non-beta-catenin dependent) pathways plays a pivotal role in the
      regulation of morphogenetic movements.

PMID- 10960784
TI  - The domineering non-autonomy of frizzled and van Gogh clones in the Drosophila
      wing is a consequence of a disruption in local signaling.
AB  - The frizzled (fz) gene is required for the development of distally pointing hairs
      on the Drosophila wing. It has been suggested that fz is needed for the
      propagation of a signal along the proximal distal axis of the wing. The
      directional domineering non-autonomy of fz clones could be a consequence of a
      failure in the propagation of this signal. We have tested this hypothesis in two
      ways. In one set of experiments we used the domineering non-autonomy of fz and
      Vang Gogh (Vang) clones to assess the direction of planar polarity signaling in
      the wing. prickle (pk) mutations alter wing hair polarity in a cell autonomous
      way, so pk cannot be altering a global polarity signal. However, we found that pk
      mutations altered the direction of the domineering non-autonomy of fz and Vang
      clones, arguing that this domineering non-autonomy is not due to an alteration in
      a global signal. In a second series of experiments we ablated cells in the pupal
      wing. We found that a lack of cells that could be propagating a long-range signal
      did not alter hair polarity. We suggest that fz and Vang clones result in altered
      levels of a locally acting signal and the domineering non-autonomy results from
      wild-type cells responding to this abnormal signal.

PMID- 10960785
TI  - The mouse Pdgfc gene: dynamic expression in embryonic tissues during
      organogenesis.
AB  - The signaling activity of Platelet-derived growth factors A and B (PDGF-A and
      PDGF-B) that is mediated through the two receptor kinases, PDGFR-alpha and PDGFR
      beta has been shown to be critical for the development of the cardiovascular
      organs, the kidney, the lung and the central nervous system. During the cloning
      of genes for VEGF related proteins, we isolated a mouse cDNA that can encode for
      a protein of 345 amino acids. A comparison of the amino acid sequence reveals
      that this predicted gene product displays 95% identity to human PDGF-C. The mouse
      Pdgfc gene maps to a region of chromosome 17 that is syntenic to human chromosome
      6p21.3 In E9. 5-E15.5 mouse embryo, Pdgfc is widely expressed in the surface
      ectoderm and later in the germinal layer of the skin, the olfactory and otic
      placode and their derivatives and the lining of the oral cavity. In the gut and
      visceral organs, such as the lung and the kidney, Pdgfc mRNA is first expressed
      in the endodermal epithelium and later in mesenchymal tissues associated with the
      endodermal structures. Similar to other PDGFs, Pdgfc is widely expressed in
      mesenchymal precursors and the myoblast of the smooth and skeletal muscles.
      Contrary to PDGF-A, Pdgfc is not expressed in the central nervous system, except
      in the cerebellum, and neurogenic derivatives of the neural crest cells. Pdgfc is
      also absent from the heart and the vascular endothelium

PMID- 10960786
TI  - Pattern of expression of the transcription factor Krox-20 in mouse hair follicle.
AB  - We examined the pattern of expression in hair follicles of the transcription
      factor gene Krox-20. During embryogenesis, Krox-20 is first expressed in the
      upper portion of the hair bud, then in the hair canal, in the sebaceous glands
      and in the outer root sheath. In the mature follicles, Krox-20, like Shh and
      TGFbetaRII, is also expressed in a sub-population of matrix keratinocytes located
      in a ring-like fashion in vibrissal follicles and clustered on one side of the
      papilla in pelage follicles. This polarized pattern rotates around the papilla as
      a result of sequential gene expression by individual groups of matrix cells. This
      peculiar pattern is not linked to follicle angling.

PMID- 10960787
TI  - dtrap-1 encodes a novel member of the heat shock super family of proteins and is
      expressed in derivatives of all three germ layers during Drosophila
      embryogenesis.
AB  - Heat shock proteins (Hsps) comprise a highly conserved superfamily of proteins
      that are required for stress tolerance in living cells. At physiological
      conditions, these proteins act as chaperones during protein folding and protein
      assembly processes (Parsell and Lindquist, 1993. Annu. Rev. Genet. 27, 427-496).
      Members of the subfamily of Hsp90 proteins were shown to be additionally involved
      in the presentation and structural modification of components of diverse cellular
      signal transduction pathways including steroid hormone reception and regulatory
      kinase activities (Pratt, 1993. J. Biol. Chem. 268, 21455-21458); Cutforth et
      al., 1994. Cell 77, 1027-1036; van der Straten et al., 1997. EMBO J. 16, 1961
      1997; Hunter and Poon, 1997. Trends Cell Biol. 7, 157-161). We have identified a
      Drosophila gene, called dtrap-1, which encodes a Hsp of a novel subfamily that is
      related to the Hsp90 family of proteins. During oogenesis dtrap-1 is expressed in
      nurse cells and its transcripts accumulate in the oocyte. The maternal
      transcripts remain in the egg but rapidly degrade during early embryogenesis,
      except in the posterior pole region. Zygotic expression is initiated after the
      onset of gastrulation showing dynamic patterns of transcripts in the developing
      mid- and hindgut as well as a subset of mesoderm derivatives.

PMID- 10960788
TI  - Identification of a stromal cell type characterized by the secretion of a soluble
      integrin-binding protein, MFG-E8, in mouse early gonadogenesis.
AB  - Mfge8 (milk fat globule-EGF-factor 8) encodes a soluble integrin-binding protein
      containing two Notch-like EGF domains and two discoidin domains. It mediates cell
      to-cell interaction by binding to integrin alphavbeta3 via the RGD motif of its
      second EGF domain. Mfge8 was first expressed at 10.0 dpc in cells of the coelomic
      epithelium covering the mesonephros, and at 10.5 dpc Mfge8-expressing cells were
      found in the mesenchyme underneath the coelomic epithelium of the genital ridges.
      At 11.5-12.5 dpc, Mfge8 expressing cells were found in the stromal tissues
      subjacent to the coelomic epithelium that envelop the fetal gonad of both sexes.
      MFG-E8 protein was accumulated extracellularly in the interstitial tissues at the
      boundary of the mesonephros and the genital ridges. A comparison of the
      expression domains of Mfge8 and several gene markers showed that Mfge8 expression
      did not significantly overlap with the expression domain of Wt1 or Emx2, but
      partially with that of Lhx9 in 11.5-day XY gonads. Comparison of the expression
      pattern of Mfge8 with that of Hsd3beta1 in the 12.5-day testes revealed that the
      Mfge8-positive cells constitute a previously uncharacterized somatic cell type
      which is distinct from Sertoli cells, Leydig cells, peritubular myoid cells and
      the endothelial cells.

PMID- 10960789
TI  - A serum response factor homologue is expressed in ectodermal tissues during
      development of the crustacean Artemia franciscana.
AB  - Complementary DNA clones have been isolated from the crustacean Artemia
      franciscana coding for a serum response factor (SRF)-homologue that is more than
      96% identical to human and Drosophila melanogaster SRFs in their MADS boxes. The
      SRF homologue is expressed in ectodermal tissues, as determined by in situ
      hybridization experiments. A SRF-binding site has been identified in the promoter
      region of the Actin403 gene that is also expressed in ectodermal tissues, in
      accordance with its transcriptional regulation by the SRF homologue. The mRNA
      coding for A. franciscana SRF is present at similar levels in cryptobiotic
      encysted embryos and in developing nauplii. However, there is a significant
      increase in CArG-binding activity at the later developmental stage, indicating a
      postranscriptional regulation of SRF during A. franciscana embryonic development.

PMID- 10960790
TI  - odd-skipped is expressed in multiple tissues during Drosophila embryogenesis.
AB  - The odd-skipped (odd) gene encodes a zinc finger protein that represses other
      segmentation genes in the early Drosophila embryo. Though odd is initially
      expressed in a striped pattern that reflects its function within the segmentation
      hierarchy, it is also expressed in a variety of patterns during later stages of
      embryogenesis. To identify the cells and tissues that correspond to these latter
      patterns, we examined the distribution of the Odd protein at all embryonic
      stages. Our results indicate that Odd is a specific and persistent marker for
      subsets of cells in developing mesoderm, ectoderm, and neural tissue. We conclude
      that Odd is a useful tool for studying cell specification, cell migrations and
      morphogenetic movements during organogenesis of the heart, gut and central
      nervous system.

PMID- 10960791
TI  - Expression and genomic characterization of protein phosphatase inhibitor-1: a
      novel marker for mesothelium in the mouse.
AB  - Protein phosphatase inhibitor-1 (inhibitor-1 or I-1) is involved in signal
      transduction and is an endogenous inhibitor of protein phosphatase-1. The mouse I
      1 protein sequence has been deduced from cDNA and is strongly homologous to the
      published rat sequence. A mouse genomic library was screened, and the I-1 gene
      was characterized and localized by fluorescent in situ hybridization (FISH) to
      chromosome 15F. Protein expression in a range of embryonic and adult tissue was
      analysed using confocal microscopy. Inhibitor-1 is expressed by: the coelomic
      epithelium; the epithelial bounding layer of cells of the kidney, lung, liver,
      heart, intestine and gonad; and the surface ectoderm. The blast cells of the
      kidney do not express I-1. We conclude that I-1 is a marker for mesothelium.

PMID- 10960792
TI  - Xenopus crescent encoding a Frizzled-like domain is expressed in the Spemann
      organizer and pronephros.
AB  - The Spemann organizer can be subdivided into head- and trunk-inducing tissues
      along the anteroposterior axis (Mangold, 1933. Naturwiisenschaften 43, 761-766;
      Spemann, 1931. Wilhelm Roux Arch. Entwicklungsmech. Org. 123, 389-517). Recent
      studies have suggested that head formation is brought about by repression of both
      Wnt and BMP signalling (Glinka et al., 1998. Nature 391, 357-362; Glinka et al.,
      1997. Nature 389, 517-519). Several Wnt inhibitors secreted from the head
      organizer region have been identified in Xenopus, such as Cerberus (Bouwmeester
      et al., 1996. Nature 382, 595-601), Frzb-1 (Leyns et al., 1997. Cell 88, 747-756;
      Lin et al., 1997. Proc. Natl. Acad. Sci. USA 94, 11196-11200), and Dkk-1 (Glinka
      et al., 1998. Nature 391, 357-362), supporting this two-inhibitor model. To
      isolate genes expressed in the head organizer, we screened a prechordal plate
      cDNA library by sequencing and expression pattern, and isolated the Xenopus
      ortholog of chick crescent encoding a Frizzled-like domain that is related to Wnt
      binding regions of the Frizzled-family proteins. Expression of Xenopus crescent
      was first detected in the Spemann organizer region at the early gastrula stage
      and later in prechordal plate cells lining the boundary of mesoderm and ectoderm
      layers and in the anterior endoderm. At tailbud stages, the expression in the
      endomesoderm region was diminished, while expression in the pronephros became
      detectable. In animal cap assays, crescent gene was synergistically upregulated
      by coexpression of Xlim1, Ldb1, and Siamois, but not by Activin treatment.

PMID- 10960793
TI  - Paraxis is expressed in myoblasts during their migration and proliferation in the
      chick limb bud.
AB  - The Paraxis gene encodes a basic helix-loop-helix (bHLH) transcription factor
      expressed in paraxial mesoderm and whose mutant displays an inability to form
      epithelial somites. We analyzed the later expression pattern of Paraxis
      transcripts in the chick limb. Paraxis transcripts are located in the Pax3
      expressing myoblasts migrating from the somites and persist in proliferating
      myoblasts in the limb bud. Moreover, the QH1 antibody, which recognizes quail
      endothelial cells, reacts with a subset of the Paraxis/Pax3 expressing cells in
      the quail limb. Paraxis is then down-regulated during muscle differentiation.

PMID- 10960794
TI  - Xenopus Six1 gene is expressed in neurogenic cranial placodes and maintained in
      the differentiating lateral lines.
AB  - Six genes are homeobox-containing transcription factors, many of which are
      expressed in head structures. We isolated a full-length cDNA of a previously
      unknown Xenopus member of this family. It shares a high sequence homology with
      mouse and human Six1, which during development are expressed in mesoderm and
      muscle. In contrast, XSix1 is prominently expressed in all neurogenic cephalic
      placodes and lateral line primordia from neurula to tadpole stages. The neurons
      derived from these placodes do not express XSix1, but the lateral line
      mechanoreceptors maintain expression. XSix1 is weakly expressed in muscle later
      in development.

PMID- 10960796
TI  - Editorial

PMID- 10960795
TI  - Developmental expression of the Xenopus Nkx2-1 and Nkx2-4 genes.
AB  - The homeodomain transcription factor Nkx2-1 (TTF-1) plays an essential role in
      the development of the thyroid, lung and ventral forebrain. We report the cloning
      and developmental expression patterns of two Xenopus NK-2 genes, Nkx2-1 and Nkx2
      4, that are closely related to Nkx2-1. These genes show readily distinguishable
      expression patterns during development. Similar to its orthologues in chicken and
      mouse, the Xenopus Nkx2-1 gene is expressed in the developing thyroid, lung, and
      ventral forebrain. In contrast, expression of Nkx2-4 is specifically localized to
      the ventral diencephalon.

PMID- 10960797
TI  - The application of the principles of geriatrics to the management of the older
      person with cancer.
AB  - Is the patient going to die of cancer or with cancer? Is the patient going to
      suffer pain and disability due to cancer? Is the patient able to tolerate
      aggressive life-prolonging treatment? This paper tries to reply to the
      fundamentals of these questions by introducing the multidimensional assessment
      that evaluates areas where age-related changes are more likely. Chronologic age
      cannot be used to predict the degree of comorbidity and of functional
      deterioration of the single individual up to age 85 at least. Assessment of aging
      includes health, functional status, nutrition, cognition, socio-economic and
      emotion evaluations. This multidisciplinary assessment is referred to as
      comprehensive geriatric assessment (CGA). The risk of comorbid conditions
      increases with age and may result in underdiagnosis: in older patients, new
      symptoms may not be clearly recognized by the patient and may be dismissed by
      practitioners as manifestations of preexisting conditions. A meaningful
      assessment of comorbidity may be obtained with a comorbidity index. The Charlson
      scale and the Chronic Illness Rating Scale - Geriatric (CIRS-G), have enjoyed the
      widest acceptance. The Instrumental Activities of Daily Living (IADL) and the
      Activities of Daily Living (ADL) are the most sensitive assessment of function in
      older individuals. IADLs include shopping, managing finances, housekeeping,
      laundry, meal preparation, ability to use transportation and telephone and
      ability to take medications: in simple words, the IADLs are those skills a person
      needs to live independently. ADLs include feeding, grooming, transferring,
      toileting and are the skills necessary for basic living. Though a correlation
      exists among comorbidity, performance status, ADL and IADL, this correlation is
      not strong enough to be reflected in a single parameter. The Folstein Mini Mental
      Status (MMS), is the instrument of most frequent use to screen older individuals
      for dementia. The main problem with the MMS is lack of sensitivity to early
      stages of dementia. The Geriatric Depression Scale (GDS), a simple tool that can
      be completed by most patients at home, doubles the rate of detection of
      depression. The Mini Nutritional assessment is very sensitive to screen older
      persons for malnutrition. The risk of polypharmacy increases with age and partly
      results from the fact that older patients visit different practitioners. A CGA
      should also include evaluation of the so called Geriatric Syndromes like
      delirium, incontinence, osteoporosis, all of which represent a hallmark of
      frailty. The CGA may help the management of older individuals with cancer in at
      least three areas: detection of frailty, treatment of unsuspected conditions,
      removal of social barrier to treatment.

PMID- 10960798
TI  - Cancer in the elderly: assessing patients for fitness.
AB  - As aging is highly heterogeneous, the clinical evaluation of the older person
      with cancer is influenced by several factors including comorbid conditions,
      disabilities, tumour type and stage. Assessment of comorbidity and disability
      represent on evolving area of research. Results from geriatrics are now
      translating in clinical oncology. Instruments for measurement of comorbidity and
      disability have been evaluated in the older cancer patients with promising
      results. The use of comprehensive geriatric assessment (CGA) in the older cancer
      patient represents a major improvement in the oncological practice. CGA is based
      on standardised interviews and covers areas of physical and psychical
      dysfunction. Moreover, CGA allows the collections of homogeneous information
      among different centres and recognition of the frail elderly. A diffuse ageistic
      prejudice may prevent adequate evaluation and treatment of older individuals. A
      wide based educational effort may allow a more appropriate management of the
      older cancer patient.

PMID- 10960799
TI  - Relative survival in elderly European cancer patients: evidence for health care
      inequalities. The EUROCARE Working Group.
AB  - This paper examines the survival of elderly European cancer patients, on the
      basis of the EUROCARE II results. Using Hakulinen and Abeywickrama's method, the
      relative survival rates at 1 and 5 years from diagnosis were computed by sex and
      quinquennial age group for the elderly (65-99 years old). Age-standardised rates
      for the whole elderly group were also calculated. The analysis covered: all
      malignancies combined, stomach, colon, rectum, pancreas, lung, melanoma, bladder,
      kidney and non-Hodgkin's lymphomas for both sexes; prostate and larynx for men;
      and breast, ovary, uterine cervix and corpus for women. Data relating to 701521
      cancer patients came from 44 population-based cancer registries in 16 European
      countries. The relative risks of death (RRs) of older patients (65-99) with
      respect to middle-aged adults (55-64) were computed by sex and country, for all
      malignancies only. The most prominent finding was the decrease in survival rates
      with increasing age for almost all cancer sites. The age-curves of survival rates
      at 1 year from diagnosis usually had a steeper slope than those at 5 years,
      particularly in women. This suggests that disease stage at presentation plays an
      important role in determining survival, particularly in the elderly. Thus, all
      factors which influence timing diagnosis in the elderly and cause a delay in
      tumour detection, such as psycho-social factors, access to care, co-morbidities
      and other clinical features affecting performance status, are very important
      predictors of prognosis. Very large geographic variations in relative survival
      rates were found among European countries. The ordering of countries was similar
      for almost all cancer sites. Western and Central Europe generally had the best
      survival, followed by Northern countries and by Southern ones (the latter with
      survival around the European average: 39% in men, 47% in women). The UK had
      survival rates unexpectedly lower than rates of nearest nations, often below the
      European average. Eastern countries usually had the lowest rates. In the very
      elderly patients (over 85 years), an apparent rise in the survival rates was
      noted, particularly at 5 years from diagnosis and in men. This 'too good'
      survival is unlikely to be due to real better prognosis, but rather to a
      selection bias. Countries with this unusual rise are also those registering a
      high proportion of DCO cases (those cases retrieved by death certificate only)
      (around 10%) or DCO unavailable. Another 'natural' bias has also to be taken into
      account: in elderly patients with a very bad prognosis, who are often suffering
      from other serious co-morbid conditions, cancer diagnoses could be under-notified
      and not reach at all the data sources commonly monitored by cancer registries.

PMID- 10960800
TI  - Measurement and impact of comorbidity in older cancer patients.
AB  - As the world population ages, oncologists are increasingly confronted with the
      problem of comorbidity in cancer patients. This has stemmed an increasing
      interest into approaching comorbidity in a systematic way, in order to integrate
      it in treatment decisions. So far, data on the subject have been widely scattered
      through the medical literature. This article is aimed at reviewing the available
      data on the interaction of comorbidity and prognosis. This overview should
      provide an accessible source of references for oncological investigators
      developing research in the field. Various methods have been used to sum
      comorbidity. However, a major effort remains to be done to analyze how various
      diseases combine in influencing prognosis. The main end-point explored so far is
      mortality, with which comorbidity globally is reliably correlated. A largely open
      challenge remains to correlate comorbidity with treatment tolerance, and
      functional and quality of life outcomes, as well as to integrate it in clinical
      decision-making.

PMID- 10960801
TI  - Advances in the systemic treatment of cancers in the elderly.
AB  - Cancer is a disease of the elderly. More than 50% of all cancers and deaths occur
      in people over 65 years. Older cancer patients are less likely to be referred to
      centers or to be given adequate chemotherapy. The elderly are under-represented
      in Phase I and II trials. Some of this hesitancy to give chemotherapy is related
      to the increased presence of co-morbid conditions in the elderly. Toxicity is
      another concern. This review summarizes data from literature on the
      effectiveness, outcome, and toxicity of chemotherapy in selected tumors.
      Information is presented on age related effects. In addition, a summary of new
      agents and biologics is presented that needs to be looked at for age related
      effects. Some comments are made on the pharmacokinetic impact of physiologic
      changes in the elderly on chemotherapy drugs. As the world's population ages, we
      need to include the elderly in trials to get data on age related effects. Most of
      the information presented shows that effective chemotherapy can be given safely
      to the elderly and the outcomes and toxicity are equivalent for many of the
      common solid tumors.

PMID- 10960802
TI  - Chemotherapy of advanced non small cell lung cancer in the elderly: an update.
AB  - In the last years there has been a growing awareness in the oncological community
      about the size of the problem of cancer in the elderly. More than 30% of lung
      cancers arise in patients aged 70 years or more. Elderly patients tolerate
      chemotherapy poorly and are not considered eligible for aggressive cisplatin
      based chemotherapy in clinical practice. A few papers have been published on
      chemotherapy of elderly NSCLC patients. Cisplatin based chemotherapy seems to be
      tolerated poorly. Vinorelbine as a single agent showed active and good tolerance.
      A phase III randomized trial, named ELVIS (Elderly Lung Cancer Vinorelbine
      Italian Study), showed a survival and quality of life benefit of vinorelbine
      versus supportive care. Among the new drugs gemcitabine can be considered more
      promising. Future trials should attempt to improve the results of vinorelbine
      chemotherapy and include geriatric and quality of life evaluations.

PMID- 10960803
TI  - Health care delivery in the older person with cancer.

PMID- 10960804
TI  - [The quality of trichiasis surgery in the kingdom of Morocco].
AB  - In December 1998, a survey was carried out on the quality of trichiasis surgery,
      based on a random sample of 750 people chosen from the surgical records of 13
      health centres of the provinces of Zagora and Errachidia (Kingdom of Morocco).
      Among those, 740 people were examined (participation ratio: 98.6%). The study
      population was mainly composed of women (63.8%) and people > 40 years (83.5%).
      The average age was 51.8 (48.5 for women and 57.4 for men). The most common
      surgical technique was the bilamellar tarsal rotation procedure. In 98.7% of
      cases, the operation concerned one of the upper eyelids, and in 58.5% of cases
      the right eye. At the time of the interviewers' visit, 11.1% of the people
      examined were blind (vision < 1/20 for the best eye) and 28.9% were visually
      impaired (vision > 1/20 but < 3/10). In addition, 17.6% of the eyes whose eyelids
      had been operated on rated as blind and 29% of them as visually impaired. The
      definition of recurrence was the presence of at least one or more eyelashes in
      contact with the eyeball. The recurrence rate is estimated to be 15.8%, divided
      into 2 categories: (1) Severe or total recurrence (2.4%) - At least one eyelash
      from the median part of the lid margin is in contact with the cornea - and, (2)
      Partial recurrence "One or more eyelashes affect the corners of the eyelids but
      never rub against the cornea" (13.4%). 14. 3% of the patients operated on were
      removing their eyelashes regularly which is a clear indicator of the failure of
      the operation. The following constitute risk factors for recurrence: being aged
      over 40, having been operated on in Errachidia province, having been operated on
      by a general practitioner or by an ophthalmologist. However, "time elapsed since
      the operation" does not appear to influence the recurrence rate in each of the
      three cohorts which were subsequently formed using the date of the operation
      (retrospectively). Most recurrences seem to develop during the first twelve
      months after the operation. The post-operational complications/sequelae detected
      were rarely sight-threatening, except in four cases, i.e., three ptoses and one
      case of tegumental necrosis with permanent exposure of the cornea. The most
      common complications were excessive rotation of the lid margin (over-correction)
      (2.3%) and cutaneous necroses with no exposure of the cornea (3.6%). In this
      series, 15.7% of the eyes examined presented central corneal opacity and 2.1%
      xerosis. In 1.6% of cases the eyeball was either destroyed (phthisis bulbi) or
      absent. A majority of patients (51.8%) was affected by persistent lacrimation or
      secretions.

PMID- 10960805
TI  - [Empyema caused by Staphylococcus aureus in children: the experience of the
      Albert Royer Children's Hospital at Fann University Hospital, Dakar].
AB  - We report a retrospective study of 58 cases of empyema caused by Staphylococcus
      aureus at the Albert Royer Children's Hospital at the Fann University Hospital,
      between January 1st 1992 and December 31st 1995. Staphylococcus aureus is the
      principal bacterium responsible for pleural effusions in children (54%), way
      ahead of Streptococcus pneumoniae (19%). Most of the children affected (86%) are
      less than 30 months old. Theses infections are often serious due to the
      resistance of the bacterium to the usual antibiotics, the lack of solid research
      data and mechanical complications associated with the effusion. Treatment is
      based on the use of an appropriate bactericidal antibiotic treatment and pleural
      drainage.

PMID- 10960806
TI  - ["CLAPSEN", a global approach to the rehabilitation of severe childhood
      malnutrition in Bolivia].
AB  - The "CLAPSEN" approach was developed at the Hospital Materno Infantil German
      Urquidi in Cochabamba, to provide a global response for the study and treatment
      of childhood malnutrition. "CLAPSEN" is short for Clinical, Laboratory,
      Anthropometry, Psychology, Sociology, Nursing (Enfermera in Spanish) and
      Nutritional care. Most of the malnourished children admitted to Cochabamba
      Hospital are from poor families, more than three quarters of whom have only
      recently arrived in the city. Acute malnutrition is just one of the
      manifestations of a generally unfavorable environment. Malnutrition should not be
      considered as a simple deficiency in energy, protein or micronutrients, but
      rather as a multi-deficiency syndrome, also involving a lack of basic health and
      social care. This study demonstrates that malnourished children display a
      considerable degree of psychological retardation and of immune system depression.
      After five weeks of rehabilitation, the children were considered to have
      recuperated physically, as assessed by anthropometry, but not psychologically, as
      assessed by the adapted Dewer Score, or immunologically, as shown by the size of
      the thymus or the extent of maturation of lymphocytes. This strategy was not
      designed as a long-term approach for treating malnutrition, but rather as a
      research project to characterize the children arriving at the hospital, to
      determine the reasons for their malnutrition and to identify strategies that
      could be implemented earlier by health centers of social services, to prevent
      deterioration in the condition of these children to severe malnutrition requiring
      hospital admission. We believe that, in this Latin American context, in which the
      rate of acute malnutrition is low, the hospital should continue to be involved in
      the treatment of severely malnourished children with associated diseases. The
      child's stay in hospital should be short and once the child has recovered
      clinically, he should be sent home. In light of the observed levels of social
      deprivation, psychosocial and immune deficits, there appears to be a need for
      continued support for the family, to ensure the full recovery of the child and to
      prevent relapses.

PMID- 10960807
TI  - [Preventing the transmission of HIV-1 from mother to child in Africa in the year
      2000].
AB  - African women of childbearing age are particularly vulnerable to HIV infection,
      and this has led to an increase in the number of pediatric HIV infections
      reported due to the risk of mother-to-child transmission (MTCT) of HIV during
      pregnancy, delivery and breastfeeding. Various approaches to preventing MTCT have
      been, or are being, evaluated in developing countries, especially in Africa. New
      data from these trials are becoming available and have implications for
      population-based intervention programs that require urgent consideration. We
      performed a critical review of 18 randomized trials and other relevant studies
      from developing and industrialized countries, to assess public health
      perspectives and to identify new research issues. Most African results relate to
      trials of antiretroviral drugs (ARVs) given to mothers during the last month of
      pregnancy, and for up to one week after delivery, and to the neonate during the
      first week of life, or simpler and shorter regimens. They indicate that
      zidovudine treatment, with or without lamivudine, and nevirapine treatment given
      alone, reduce transmission during the first six months of life by 30 % to 50%.
      Preliminary results suggest that zidovudine treatment is effective in the long
      term. One randomized study showed that the replacement of breast feeding with
      breast milk substitutes was effective at reducing the overall risk of MTCT.
      Antiseptic disinfection and micronutrient supplementation have been shown to
      reduce maternal and infant mortality and morbidity, but not the MTCT of HIV.
      Voluntary, confidential HIV counseling and testing for pregnant women, a short
      course of peripartum ARVs and alternatives to breast feeding such as early
      weaning and breast milk substitutes from birth, are currently the best means of
      reducing the MTCT of HIV in Africa. Pilot programs based on these findings are
      currently being implemented in several African countries. Prevention of the MTCT
      of HIV should also be considered as part of the wider management of maternal and
      infant health during prenatal, delivery and postnatal care. Several complementary
      issues require further investigation. Some results, such as the long-term
      efficacy of a short course of ARVs once the mother has finished breast feeding,
      and the long-term safety of these treatments, require confirmation. Further
      studies are required into the prevention of postnatal transmission, particularly
      in light of the unknown consequences of different feeding options and the
      possibility of post-perinatal prophylaxis with ARVs. The reduction of MTCT of HIV
      in Africa is a true challenge in efforts to control the HIV pandemic, but recent
      progress in the identification of effective treatments provides some hope. Large
      scale implementation of these new treatments is required, and should provide
      practical information and perhaps identify more potent, and possibly cheaper,
      strategies.

PMID- 10960808
TI  - [Brazil, land of human and health contrasts].

PMID- 10960809
TI  - [Infant mortality rate and social disparity at Recife, the metropolis of the
      North-East of Brazil].
AB  - We analyzed differences in infant mortality between areas of Recife, a city in
      the North East of Brazil, analyzing the relationship between living conditions
      and the risk of death. We compared infant mortality coefficients for 1995 with
      indicators of living conditions and collected data for the 770 infant deaths and
      the 27,965 live births. Neighborhoods were ranked according to the quality of
      living conditions and were grouped into four clusters. The infant, neonatal and
      postneonatal mortality coefficients were 27.53, 18.84 and 8.69 per 1,000 live
      births respectively. Lower quality living conditions were associated with higher
      coefficients. The main causes of infant deaths were perinatal disorders, the
      coefficient of which was 14.95 per 1,000 live births, followed by congenital
      malformations, gastroenteritis and bronchopneumonia. With the exception of
      congenital malformations, the coefficients of all these causes of death increased
      as living conditions worsened. These inequalities are generally obscured by the
      presentation of means for the city as a whole.

PMID- 10960811
TI  - [Intestinal parasite infections and schistosomiasis in a poor urban area, in
      townships of the sugar cane belt and in villages of the semi-arid area of North
      East Brazil].
AB  - We determined the prevalence of intestinal parasite infections between 1993 and
      1998 in the populations of a poor quarter of Recife (Pernambuco), in two
      townships in the sugar cane belt and in three villages of the semi-arid area far
      from the coast. Intestinal schistosomiasis was present in the sugar-growing area
      but was not observed in the populations inland that use dams to provide
      irrigation and fishing. Ascaris was very common in the city and the sugar cane
      belt and large numbers of hookworms were observed, especially in the sugar
      growing area. These nematodes were very rare in the semi-arid area. This
      distribution probably results from both climatic conditions and human behavior.
      The high frequency of Amoeba cysts demonstrates that the peasants, farmers and
      fisherman living in these areas have poor hygiene practices. There are probably
      many, complex relationships between education, income, lifestyle and intestinal
      parasite infections.

PMID- 10960810
TI  - [American cutaneous leishmaniasis in the sugar cane-producing area of Pernambuco,
      North-East Brazil].
AB  - The cases of American cutaneous leishmaniasis reported here were observed between
      1995 and 1998 in outpatients at a health clinic in the sugar cane-producing
      region in the south of Pernambuco State (Brazil), in which the disease is known
      to be endemic. Two hundred thirty eight cases were reported, equivalent to about
      ten cases per thousand patients. The disease affected patients of all ages, with
      a slight male predominance. The lesions were generally single and located on the
      legs. They were successfully treated with Glucantime. Vectors of the disease,
      sandflies of the genus Lutzomyia, were captured in and around homes, particularly
      in stables. This field work demonstrates the extent of a long-standing endemic
      that can be effectively treated within motivated health structures.

PMID- 10960812
TI  - [Overview of the geography of intestinal schistosomiasis in Brazil].
AB  - The distribution of schistosomiasis in Brazil is highly contrasted, with most
      cases concentrated in a large area in the North East, where the disease is
      endemic and considered a major threat to public health, and small isolated foci
      of disease scattered throughout the country seen as being of little
      epidemiological importance. The common interpretation of the history of this
      endemic disease (that it began in the endemic zone and has spread to the isolated
      foci) has added to the stigmatization of the North East. However, this
      interpretation is challenged by many examples of the recent establishment of the
      disease in the North-East and its more long-standing nature in the isolated foci.
      Besides, overstressing the role of recent migration simply obscures both social
      issues and the biogeography of vectors. Areas are not homogeneous in terms of
      schistosomiasis and we must therefore consider these factors if we are to
      understand the spread of the disease and its current distribution. Thus, in
      Amazonia, low human population pressure and the rarity of snails (mainly due to
      the acidity of the water) together account for the low level of transmission
      despite the high proportion of infected individuals among immigrants to this
      area. The converse is true for the city of Belem. Very similar reasons can be
      given for the limited impact of schistosomiasis in the central plateau and its
      high frequency around the federal capital, Brasilia. In contrast, the rate of
      infection is not very high around Sao Paolo due to the specific characteristics
      of urbanization of this city and its highly efficient control program. However,
      the enormous size of this city results in the number of cases reported being
      similar to that for Belem or Brasilia. These three cities are linked by a
      highway, which serves as a major axis for migration, particularly for those
      heading north from southern Brazil or Sao Paolo. This migration axis has
      increased in importance because there are now far fewer opportunities to settle
      in the West (Amazonia and the central plateau). The older "endemic territory" of
      the North East is experiencing a process of concentration of its cases of
      schistosomiasis in its larger cities, Recife and Salvador in particular. Thus,
      this endemic disease is becoming more urban and a network of five major cities,
      widely dispersed geographically, with high levels of infection, is emerging.

PMID- 10960813
TI  - [Intestinal schistosomiasis and its control in North-East Brazil].
AB  - Intestinal schistosomiasis is endemic in the sugar cane belt near the coast of
      North-East Brazil. The environment and poor living conditions of the agricultural
      workers of this area combine to perpetuate the transmission of this disease.
      However, a new epidemiological pattern is emerging on the coast of Pernambuco
      State, where workers from the endemic area are building weekend homes without
      proper drainage. National control programs have led to a dramatic reduction in
      severe infections. However, they have not yet succeeded in stopping disease
      transmission altogether. The transfer of responsibility for control to local
      public health structures, which is currently underway, should improve the
      situation.

PMID- 10960814
TI  - [Who uses the public health service? An example from North-East Brazil].
AB  - We questioned the users of two public health centers in the city of Recife, North
      East Brazil, and a third center in a small neighboring town, about their level of
      education, their activities, incomes and perception of the functioning of the
      public health service. Overall, the users of the service, who were mostly women,
      gave a positive opinion of its functioning. However, the population as a whole
      perceived use of the public health service to be associated with poverty and
      social exclusion.

PMID- 10960815
TI  - [Hospital function and the urban system in Brazil].
AB  - Do hospital services, like other services and commerce, contribute to the
      structuring of geographical regions, as proposed by central place theory? This
      question raises the issue of the rating of hospital facilities in land use
      planning policies. According to the theory, a polarized region forms around a
      central place due to the minimization of transport costs by consumers seeking to
      satisfy their needs. If a center offers more central functions (rare trades,
      services for individuals and businesses), its level in the urban hierarchy is
      raised and its area of influence expands. This theory was validated using a
      model, the variant of the gravitation model proposed by Huff. Brazil is an
      excellent testing ground for these hypotheses due to the great variety of
      geographic situations, economic and social development levels and the
      availability of sufficient data. Geographic research has resulted in the
      construction of an urban center hierarchy based on central functions, and the
      Unified Health System (or SUS) systematically records authorizations for hospital
      admission (or AIH) throughout the country. Processing of the 12 million AIH for
      1996 showed that in a quarter of cases, the individual was admitted to hospital
      in a town other than their town of residence (exogenous AIH). Mapping the
      percentage of exogenous AIH makes it possible to delimit the area of influence of
      health services (observed influence) for the whole of Brazil. In Minas Gerais
      State, these areas of influence were compared with the estimates made according
      to the Huff model (calculated influence), with adjustment for distance and the
      number of hospital beds. Differences between the observed and calculated areas of
      influence are due to factors not taken into account by the model, such as the
      heterogeneity of many regions in the country. However, the accuracy of the
      estimation is satisfying, as is the simplicity of the equations. All the results
      tend towards a single conclusion: hospital services play a major role in the
      structuring of geographic space, by increasing the attraction potential of urban
      centers.

PMID- 10960816
TI  - Selective ablation of orthodontic composite by using sub-microsecond IR laser
      pulses with optical feedback.
AB  - BACKGROUND AND OBJECTIVE: Conventional methods of residual composite removal
      after debonding orthodontic brackets involve the use of abrasives that damage the
      underlying enamel. The objective of this study was to determine whether infrared
      pulsed lasers are suitable for the removal of composite through selective laser
      ablation. STUDY DESIGN/MATERIALS AND METHODS: Pulsed CO(2) and Er:YAG lasers were
      evaluated for their ability to selectively ablate orthodontic composites. Optical
      emission spectra of the luminous plasma produced during composite and enamel
      ablation were acquired to differentiate between enamel and composite ablation to
      minimize accidental removal of enamel. RESULTS: TEA CO(2) laser pulses at a
      wavelength of 10.6 microm were best suited for the selective ablation of
      composite. Spectral analysis of plume emission identified several calcium
      emission lines that can potentially be used to distinguish between enamel and
      composite ablation. CONCLUSION: TEA CO(2) lasers operating at 10.6 microm used in
      conjunction with optical feedback have the potential to selectively ablate
      residual dental composite and minimize inadvertent removal of enamel.

PMID- 10960817
TI  - Sealant bond strengths of CO(2) laser-etched versus acid-etched bovine enamel.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate sealant shear
      bond strength on bovine enamel with standard acid etching compared with CO(2)
      laser etching. STUDY DESIGN/MATERIALS AND METHODS: Bovine enamel was prepared
      either by acid or laser etching and divided into four experimental groups, either
      acid or laser-etched teeth with or without a primer. A gelatin capsule was used
      to place the sealant on the prepared enamel surface and the bond tested in shear.
      Also surface roughness was evaluated by using a surface analyzer and an atomic
      force microscope. RESULTS: Shear bond strength results were the following: acid
      etch = 8.8 +/- 3.8 MPa, acid etch with primer = 10.3 +/- 5.5 MPa, laser etch =
      4.0 +/- 1.1 MPa, and laser etch with primer = 6.2 +/- 2.3 MPa. Analysis of
      variance statistical analysis found no significant difference in bond strength
      between the acid-etched groups. However, the laser-etched groups had
      significantly lower bond strengths from the acid-etched teeth. In addition, a
      significant difference was observed between the laser-etched groups, where the
      use of the primer helped to increase the bond strength of the sealants. The
      surface roughness was significantly greater on the laser-etched teeth at the
      microm level (by using a surface analyzer) from the acid-etched and the control
      specimens. No difference in roughness (by using an atomic force microscope) was
      observed at the nanometer level between the laser and acid-etched teeth.
      CONCLUSION: For these particular settings, the laser-etched teeth resulted in
      lower bond strengths to enamel and the use of a primer increased the bond
      strength for laser-etched teeth only.

PMID- 10960818
TI  - Optical and thermal properties of nasal septal cartilage.
AB  - BACKGROUNDS AND OBJECTIVES: The aim of the study was to measure the spectral
      dependence of optical absorption and reduced scattering coefficients and thermal
      conductivity and diffusivity of porcine nasal septal cartilage. Values of optical
      and thermal properties determined in this study may aid in determining laser
      dosimetry and allow selection of an optical source wavelength for noninvasive
      diagnostics for laser-assisted reshaping of cartilage. MATERIALS AND METHODS: The
      diffuse reflectance and transmittance of ex vivo porcine nasal septal cartilage
      were measured in the 400- to 1,400-nm spectral range by using a
      spectrophotometer. The reflectance and transmittance data were analyzed by using
      an inverse adding-doubling algorithm to obtain the absorption (mu(a)) and reduced
      scattering (mu(a)') coefficients. A multichannel thermal probe controller system
      and infrared imaging radiometer methods were applied to measure the thermal
      properties of cartilage. The multichannel thermal probe controller system was
      used as an invasive technique to measure thermal conductivity and diffusivity of
      cartilage at three temperatures (27, 37, 50 degrees C). An infrared imaging
      radiometer was used as a noninvasive method to measure the thermal diffusivity of
      cartilage by using a CO(2) laser source (lambda = 10.6 microm) and an infrared
      focal plane array (IR-FPA) camera. RESULTS: The optical absorption peaks at 980
      nm and 1,180 nm in cartilage were observed and corresponded to known absorption
      bands of water. The determined reduced scattering coefficient gradually decreased
      at longer wavelengths. The thermal conductivity values of cartilage measured by
      using an invasive probe at 27, 37, and 50 degrees C were 4.78, 5.18, and 5.76
      mW/cm degrees C, respectively. The corresponding thermal diffusivity values were
      1.28, 1.31, and 1.40x 10(-3) cm(2)/sec. Because no statistically significant
      difference in thermal diffusivity values with increasing temperature is found,
      the average thermal diffusivity is 1.32 x 10(-3) cm(2)/sec. The numerical
      estimate for thermal diffusivity obtained from infrared radiometry measurements
      was 1.38 x 10(-3) cm(2)/sec. CONCLUSION: Values of the spectral dependence of the
      optical absorption and reduced scattering coefficients, and thermal conductivity
      and diffusivity of cartilage were measured. The invasive and noninvasive
      diffusivity measurements were consistent and concluded that the infrared imaging
      radiometric technique has an advantage to determine thermal properties, because
      damage to the cartilage sample may be avoided. The measured values of absorption
      and reduced scattering coefficients can be used for predicting the optical
      fluence distribution in cartilage and determining optical source wavelengths for
      the laser-assisted cartilage reshaping studies. The thermal conductivity and
      diffusivity values can play role in understanding thermal-dependent phenomenon in
      cartilage during laser irradiation and determining laser dosimetry for the laser
      assisted cartilage reshaping studies.

PMID- 10960819
TI  - Diode laser treatment of hyperplastic inferior nasal turbinates.
AB  - Background and Objective Different laser types have been used for the treatment
      of hyperplastic inferior nasal turbinates. The clinical experiences of its
      treatment by means of a diode laser are presented. Study Design/Materials and
      Methods A total of 76 patients suffering from nasal obstruction due to
      hyperplastic inferior nasal turbinates were treated with a continuous diode laser
      (wavelength of lambda = 940 nm, laser parameter 10 W/energy/turbinate 5 kJ) in
      "noncontact" mode and under local anesthesia. All patients were refractory to
      conservative medical treatment. Fifty patients (26 of 50 [52%] with allergic
      rhinitis and 24 of 50 [48%] with vasomotor rhinitis) were included into this
      clinical trial with a follow-up of 1 year. The study was conducted by a
      questionnaire, photo documentation, allergy test, mucociliary clearance test,
      rhinomanometry, acoustic rhinometry, conventional radiology of the paranasal
      sinuses, and histology. RESULTS: The mean operation time took 6 min/turbinate, no
      nasal packing was necessary and no immediate complications (e.g., major bleeding)
      were observed. During the first 2-4 weeks, nasal obstruction was correlated to
      the extent of postoperative edema and nasal crusting. Statistical analysis
      revealed significant improvement of the nasal airflow (rhinomanometry) and nasal
      cavity volume (acoustic rhinometry) 6 months and 1 year after laser surgery,
      respectively. A total of 86% of the patients described a subjective improvement
      of nasal airflow 6 months and 76% of the patients 1 year after laser treatment.
      The mucociliary function test showed no significant variation in comparison to
      the preoperative measurements 1 year after laser treatment. CONCLUSION: Diode
      laser treatment of hyperplastic inferior nasal turbinates is a useful procedure,
      which can be performed as an outpatient surgery under local anesthesia, resulting
      in a controlled coagulation and ablation of the soft tissue. The short operation
      time and the good results provide an excellent patient acceptance.

PMID- 10960820
TI  - Semi-solid albumin solder improved mechanical properties for laser tissue
      welding.
AB  - BACKGROUND AND OBJECTIVE: A semi-solid albumin solder formulated with
      hydroxypropylmethylcellulose (HPMC) was designed to improve the characteristics
      of liquid and solid solders. STUDY DESIGN/MATERIALS AND METHODS: Acute tensile
      strengths were determined on canine small bowel in vitro by using liquid 50%
      bovine serum albumin (BSA), semi-solid 48% BSA with HPMC, and solid 60% BSA
      solder. Long-term healing of liquid and semi-solid solders, compared with a
      suture control, was evaluated in a porcine skin model, with tensile strength as
      well as histologic findings obtained on postoperative day 7. RESULTS: Acutely,
      semi-solid solder demonstrated a significantly (P < 0.05) higher tensile strength
      when compared with liquid or solid solder. At 7 days, HSA semi-solid and BSA semi
      solid had significantly (P < 0.05) higher tensile strength than suture control;
      however, no differences were seen for liquid or solid solder groups. No
      differences in histology were appreciable between any of the solder groups in a
      porcine skin model. CONCLUSION: Acutely and at 7 days, semi-solid solder was
      stronger than 50% liquid albumin with better handling characteristics.

PMID- 10960821
TI  - Novel solid protein solder designs for laser-assisted tissue repair.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have shown that the application of
      chromophore-enhanced albumin protein solders to augment laser tissue repairs
      significantly improves repair strength, enhances edge co-optation, and reduces
      thermal tissue injury. These investigations are furthered with this in vitro
      study conducted to assess a new range of specially designed chromophore-enhanced
      solid protein solders manufactured and tested for application during laser
      assisted tissue repair. STUDY DESIGN/MATERIALS AND METHODS: The experimental
      study was divided into three parts. In the first part of the study, the creation
      of a chromophore concentration gradient across the thickness of the solid protein
      solder was investigated as a means to improve control of the heat source gradient
      through the solder during laser irradiation. In the second part of the study,
      predenaturation of the solid protein solder was investigated as a means for
      enhancing the stability of the solder in physiological fluids before irradiation.
      Finally, in the third part of the study, the feasibility of using synthetic
      polymers as a scaffold for traditional albumin protein solder mixes was
      investigated as a means of improving the flexibility of the solder. RESULTS:
      Uniform denaturation across the thickness of the solder was achieved by
      controlling the chromophore concentration gradient, thus ensuring stable solder
      tissue fusion when the specimen was submerged in a hydrated environment.
      Predenaturation of the solid protein solder significantly reduced the solubility
      of the solder, and consequently, improved the handling characteristics of the
      solder. The solder-doped polymer membranes were flexible enough to be wrapped
      around tissue, whereas their solid nature avoided problems associated with
      "runaway" of the less viscous liquid solders currently used by researchers. In
      addition, the solder-doped polymer membranes could be easily tailored to a wide
      range of geometries suitable to many clinical applications. CONCLUSION: The novel
      solid protein solder designs presented here add a new dimension to tissue repair
      as their flexible, moldable, and absorption controllable nature, greatly improves
      the clinical applicability of laser-assisted tissue repair.

PMID- 10960822
TI  - Laser irradiative tissue probed in situ by collagen 380-nm fluorescence imaging.
AB  - BACKGROUND AND OBJECTIVE: There is no ideal method to detect molecular changes in
      situ of laser-irradiated tissue without removing a section of tissue for
      histologic examination. A new method is reported to evaluate laser-induced
      thermal tissue damage in situ by using 380-nm native fluorescence imaging under
      340-nm excitation. STUDY DESIGN/MATERIALS AND METHODS: Native fluorescence
      imaging was performed on laser irradiated bovine tendon tissue and compared with
      light illuminated photography and histology with picrosirius red F3BA stain.
      RESULTS AND CONCLUSION: The results indicate that a decrease in collagen
      fluorescence at 380 nm was observed in laser-induced thermally damaged tissues.
      The injured region of tissue defined by its fluorescence image coincided with an
      area defined by photography and histology.

PMID- 10960823
TI  - Optimal cryogen spray cooling parameters for pulsed laser treatment of port wine
      stains.
AB  - BACKGROUND AND OBJECTIVE: In dermatologic laser therapy, cryogen spray cooling
      (CSC) is a means to protect the epidermis while leaving dermal structures
      susceptible to thermal damage. The purpose of this study was to determine optimal
      spurt duration, tau(s), and optimal delay, tau(d), between the cryogen spurt and
      laser pulse when using CSC in treatment of port wine stain birthmarks. STUDY
      DESIGN/MATERIALS AND METHODS: A finite difference method is used to compute
      temperature distributions in human skin in response to CSC. Optimal tau(s) and
      tau(d) are determined by maximizing the temperature difference between a modeled
      basal layer and an imaginary target chromophore. RESULTS: The model predicts an
      optimal tau(s) of 170-300 msec and approximately 400 msec for shallow (150
      microm) and deeper (400 microm) targets, respectively. Spraying for longer than
      the optimal tau(s) does not critically impair cooling selectivity. For a spurt
      duration of 100 msec, optimal delays are 5-10 msec and 25-70 msec for a shallow
      and deep basal layer, respectively. CONCLUSION: In the absence of knowledge about
      the lesion anatomy, using a tau(s) of 100-200 msec and no delay is a good
      compromise. A delay is justified only when basal layer and target chromophore are
      relatively deep and the optimal spurt duration cannot be applied, e.g., to avoid
      frostbite.

PMID- 10960824
TI  - Treatment of leg telangiectasia by using a long-pulse dye laser at 595 nm with
      and without dynamic cooling device.
AB  - BACKGROUND AND OBJECTIVE: The long-pulse dye laser (PDL) at 595 nm and pulse
      duration of 1.5 msec has been shown to improve clearance of larger vessels such
      as those seen in leg telangiectasia. The objectives of this study are twofold.
      First, to determine the effect of the dynamic cooling device (DCD) in clearance
      of leg telangiectasia by using a long-pulse PDL at 595 nm. Next, to determine the
      effect of the DCD in reducing transient discomfort associated with treatment and
      in reducing epidermal damage (blistering, hyper/hypopigmentation, scarring)
      caused by the laser. STUDY DESIGN/MATERIALS AND METHODS: Matched treatment sites
      were compared at energy densities of 20 and 24 J/cm(2) with and without the use
      of the cryogen spray in 18 patients. In areas treated without the DCD, the laser
      pulse was delivered through a single layer of Spenco Second Skin. Patients
      received two treatments 6 weeks apart. Discomfort ratings, clearance of leg
      telangiectasia, and complications were assessed at 6 weeks, 12 weeks, and 6
      months. RESULTS: A reduction in discomfort ratings was found in most patients
      using the DCD. Six-month follow-up data revealed at the 20 J/cm(2) treatment
      sites, with or without the DCD, 76.9% showed greater than 50% clearance. At the
      24 J/cm(2) treatment sites, with or without the DCD, 84.6% showed greater than
      50% clearance. CONCLUSION: The long-pulse dye laser at 595 nm with a 1.5-msec
      pulse duration cleared leg telangiectasia an average of 67.5% with two treatments
      at 6 months. The major effect of the DCD was on pain reduction. There was no
      difference in clearance rates when using the DCD vs. cooled Second Skin. Further
      studies with longer cooling times with the DCD are needed to optimize treatment
      parameters.

PMID- 10960825
TI  - Liquid chromatography of natural pigments.
AB  - The newest results in the application of various liquid chromatographic
      techniques for the analysis of natural pigments in pure state and in complicated
      matrices are compiled. The methods employed for the separation and quantitative
      determination of the different pigment classes (flavonoids, coumarins,
      chlorophylls, etc.) are described and critically evaluated. The future trends are
      briefly discussed.

PMID- 10960826
TI  - Determination of amobarbital and secobarbital in plasma samples using micellar
      liquid chromatography.
AB  - A new liquid chromatographic procedure for the determination of amobarbital and
      secobarbital in plasma samples is proposed. The method uses a Spherisorb
      octadecylsilane ODS-2 C(18) analytical column, a guard column of similar
      characteristics and 0.04 M CTAB solution buffered at pH 7.5 containing 3% 1
      propanol as micellar mobile phase. The UV detection was carried out at 250 nm.
      Butabarbital was used as internal standard. Plasma samples preparation only
      required adequate dilution with the mobile phase before injection into the
      chromatographic system. The limits of detection were 0.2 and 0.4 mg/L for
      amobarbital and secobarbital, respectively. The proposed method allows the
      determination of amobarbital and secobarbital in plasma at therapeutic levels.

PMID- 10960827
TI  - Quantification of methamphetamine, amphetamine and enantiomers by semi-micro
      column HPLC with fluorescence detection; applications on abusers' single hair
      analyses.
AB  - Achiral and chiral semi-micro column high-performance liquid chromatographic
      methods with fluorescence detection to determine methamphetamine and amphetamine
      in human hair are described. These compounds were extracted into 5%
      trifluoroacetic acid (TFA) in methanol, derivatized with 4-(4,5-diphenyl-1H
      imidazol-2-yl)-benzoyl chloride and separated either on a 250 x 1.5 mm i.d.
      octadecyl-silane (ODS) or a 150 x 2 mm i.d. OD-RH column. Linear calibration
      curves extending over a wide range of concentration that covers the practical
      samples were obtained for amphetamine, methamphetamine and their enantiomers (r =
      0.999). Resolution values for amphetamine and methamphetamine enantiomers were
      3.4 and 1.1, respectively. Intra- and inter-day variations of both the methods
      were not larger than 8.9% expressed as relative standard deviations (n >/= 5).
      The limits of detection at a signal-to-noise ratio of 3 obtained by both the
      methods were in the range of 1.0-4.7 fmol/5 microL injection with the achiral
      method being more sensitive. Abusers' hair samples were analyzed by the two
      methods and only the S(+)-enantiomers were found in eight Japanese abusers' hair
      samples. The achiral method was used to study the concentrations of these
      compounds in single black and white hair strands of abusers.

PMID- 10960828
TI  - Capillary electrophoretic analysis of brimonidine in aqueous humor of the eye and
      blood sera and relation of its levels with intraocular pressure.
AB  - The aim of this study was the development of a capillary electrophoretic method
      for the determination of the levels of the selective alpha(2)-adrenergic receptor
      agonist brimonidine in aqueous humor of the eye and blood sera and their relation
      to its efficacy in reducing the intraocular pressure (IOP). Analysis of
      brimonidine was performed by capillary zone electrophoresis using 20 mM borate,
      pH 9.3, as operating buffer and detection at 255 nm. Brimonidine levels were
      determined in aqueous humor and blood sera from seven patients admitted for
      cataract extraction following ocular administration of the ophthalmic
      Alphagantrade mark solution. Levels of brimonidine and IOP values were recorded
      for a 24 h period. Alphagantrade mark administration resulted in a significant
      reduction of IOP, from within 30 min up to 4-5 h, whereafter a stepwise increase
      was recorded until 24 h, where mean IOP value returned to that before
      administration. The IOP reduction was related to the levels of brimonidine in
      aqueous humor, where maximal levels (80-100%) were obtained within 1-3 h. A 50%
      amount of the solution was determined after 4-5 h, whereas it reached the minimum
      level after 12 h. Serum levels reached maximum within 3-4 h, a 50% reduction was
      recorded in 12 h and minimum level in 24 h. It is concluded that brimonidine
      administration may significantly reduce IOP in patients when its level is
      maintained >/=50% of the maximum present in aqueous humor, i.e within a 4-6 h
      period. Since at this time the level of brimonidine in blood serum has reached
      maximum value, administration of brimonidine every 6 h may be used to obtain
      adequate brimonidine levels to maintain a constantly lowered IOP.

PMID- 10960829
TI  - Quantitative determination of melatonin in human plasma and cerebrospinal fluid
      with high-performance liquid chromatography and fluorescence detection.
AB  - A validated new and precise reversed-phase high-performance liquid
      chromatographic method for the determination of melatonin in human plasma and
      cerebrospinal fluid, with 5-fluorotryptamine as internal standard, is described.
      Liquid-liquid extraction with dichloromethane was performed under alkaline
      conditions. After evaporation of the organic solvent, the extract was dissolved
      in eluent and chromatographed on a base-deactivated octadecyl column, using an
      eluent composed of 650 mL potassium dihydrogenphosphate solution (0.07 mol/L
      water), adjusted to a pH of 3.0 with a 43% phosphoric acid solution, mixed with
      350 mL methanol. Fluorescence detection at an excitation wavelength of 224 nm and
      an emission wavelength of 348 nm was used for quantitation. Melatonin and 5
      fluorotryptamine chromatographed with retention times of 5.3 and 9. 3 min,
      respectively. Mean recoveries of 96% (n = 10) and 95% (n = 5) were found for
      melatonin in plasma and cerebrospinal fluid respectively. 5-Fluorotryptamine was
      found to have a mean recovery of 90% (n = 10) and 82% (n = 5) in plasma and
      cerebrospinal fluid, respectively. The repeatability coefficients of variation
      for both melatonin and 5-fluorotryptamine in plasma were 4-5% [five different
      samples (r = 5) on two consecutive days (n = 2)], with reproducibility
      coefficients of 1.6-7% (n = 2, r = 5) and 0.9-4% (n = 2, r = 5) for melatonin and
      internal standard, respectively. In cerebrospinal fluid the repeatability
      coefficient of variation of the extraction procedure was 5% (n = 1, r = 5) for
      melatonin and 7% (n = 1, r = 5) for 5-fluorotryptamine. The correlation
      coefficients of the calibration curves were 0.9998 (n = 2) in plasma at a
      concentration range of 0.108-25.9 ng/mL and 0.9994 (n = 2) at a concentration
      range of 0.108-25.9 ng/mL in cerebrospinal fluid. The limit of detection was
      determined at 8 pg/mL which enables to measure melatonin concentrations at
      physiological concentrations reached during daytime.

PMID- 10960830
TI  - Post-column reaction detection of biotin in human plasma ultrafiltrate based on
      laser-induced fluorescence energy transfer in the far-red spectral region.
AB  - High performance liquid chromatography followed by post-column reaction detection
      in the far-red spectral region provides added sensitivity and selectivity. A
      homogeneous fluorescence energy transfer assay in the competitive mode based on
      the binding of biotin and streptavidin was developed as an on-line post-column
      reaction detection system. The labels used for energy transfer were R
      Phycoerythrin conjugated to biotin and Cyanine 5 labeled with streptavidin. The
      energy transfer peak was measured at 670 nm and excitation was achieved using the
      488 nm line of an argon ion laser. The biotin concentration in plasma
      ultrafiltrate ranged from 0.024 to 6.12 ng/mL (n = 6). The precision of the two
      controls, 0.24 and 2. 44 ng/mL, was found to be 18.70% and 9.92% relative
      standard deviation respectively. Accuracy was 10.47% and 1.95% difference from
      spiked, respectively (n = 6). The limit of detection was 21.70 pg/mL (8.90 x 10(
      11)M) calculated based on a factor of 2x the standard deviation of the blank (n =
      6). The correlation coefficient for the calibration curve was found to be 0.9995.
      Recovery from plasma ultrafiltrate at 2.44 ng/mL was 103.40% (n = 6). Detection
      selectivity was indicated by the absence of background fluorescence in six
      different plasma samples collected from six individual donors. Endogenous levels
      were detected in two of the six pools of plasma ultrafiltrates.

PMID- 10960831
TI  - Chiral liquid chromatography tandem mass spectrometry in the determination of the
      configuration of 2-hydroxyglutaric acid in urine.
AB  - D-2-Hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria are two distinct
      inherited metabolic diseases. The accurate diagnosis of the exact disorder relies
      on the determination of the configuration of the enantiomers, either D-2
      hydroxyglutaric acid or L-2-hydroxyglutaric acid excreted in excess in urine of
      patients. The enantiomeric chiral separation of 2-hydroxyglutaric acid was
      achieved using a ristocetin A glycopeptide antibiotic silica gel bonded column.
      The chiral column was interfaced with a tandem mass spectrometer for the purpose
      of specifically detecting the eluting 2-hydroxyglutaric acid. Tandem mass
      spectrometry was employed using an electrospray ion source in the negative ion
      mode. Three parent-to-daughter transitions under collision-induced dissociation
      conditions were used to detect only 2-hydroxyglutaric acid. The two forms of the
      compound were satisfactorily separated with almost baseline resolution at 4.95
      and 5.5 min. Three known patients with 2-hydroxyglutaric aciduria were identified
      to have L-2-hydroxyglutaric aciduria. The method is simple, selective, rapid, and
      free from interference.

PMID- 10960832
TI  - High-performance liquid chromatographic assay for the determination of novel
      triazole antifungal agents in tissue. Application to tissue distribution studies.
AB  - A simple and rugged reversed-phase high-performance liquid chromatographic method
      with ultraviolet absorbance detection at 263 nm was developed and validated for
      the analysis of novel triazole antifungal agents SYN-2869 and its derivatives in
      tissues. The method involved homogenization with 0.01 M phosphate buffer (pH 7.8)
      for lung, brain and spleen tissues. The liver and kidneys were homogenized with
      acetonitrile:acetone (1:1). The plasma proteins were precipitated with ice-cold
      acetonitrile and supernatent was evaporated to dryness. The reconstituted samples
      were injected onto an HPLC system. SYN-2869 was separated from the matrix
      components on a symmetry C(18) column using a aqueous mobile phase of
      acetonitrile and water with a flow rate of 1 mL/min. A step gradient of 40-80%
      acetonitrile eluted SYN-2869 and the internal standard (SYN-2506). The linear
      range was 0.5-10 microgram/g (r(2) > 0.99). The limit of quantitation was 0.5
      microgram/g. The inter-day precision and accuracy for SYN 2869 standard
      concentration were from 2.6 to 7.4% and from -1.56 to +3.29%, respectively. The
      method was applied to tissue samples collected from single intravenous
      administration to mice to evaluate the distribution of these novel antifungal
      agents to different tissues.

PMID- 10960833
TI  - Determination of morphine 3-esters in rabbit plasma by high-performance liquid
      chromatography with ultraviolet detection.
AB  - A sensitive high-performance liquid chromatographic (HPLC) method for the
      quantitation of the morphine 3-esters 1[3-(2, 2-dimethylvaleroyl)-morphine (A), 3
      (2-phenylbenzoyl)-morphine (B) and 3-(2,2-diphenylpropionyl)-morphine (C)] in
      rabbit plasma is described. Sample preparation was based on reversed-phase solid
      phase extraction. The compounds were separated on C(18) reversed-phase analytical
      columns and then determined by ultraviolet detection. The recovery from plasma
      was 78.7 +/- 7.4%, 69.1 +/- 6.9% and 75 +/- 7.2% (mean +/- SD) for A, B, and C,
      respectively. The present method enabled the detection limit of 0.2, 0.2 and 0.1
      ng and quantification limit of 20, 10 and 10 ng/ml for A, B and C, respectively.
      The developed method was used for determination of the plasmakinetics of these
      morphine 3-esters in rabbits.

PMID- 10960834
TI  - A new sensitive determination method of estradiol in plasma using peroxyoxalate
      ester chemiluminescence combined with an HPLC system.
AB  - A new sensitive determination method of estradiol in a plasma sample using
      peroxyoxalate ester chemiluminescence was developed. Estradiol, which was
      extracted by liquid-liquid extraction using ethyl acetate from plasma, was
      derivatized with dansyl-chloride (DNS-Cl) and separated by reverse-phase HPLC.
      The performance of four oxalates, bis(trichlorophenyl)oxalate (TCPO), bis(2,4
      dinitrophenyl)oxalate (DNPO), bis(pentafluorophenyl)oxalate (PFPO), and bis[4
      nitro-2-(3,6, 9-trioxadecyloxycarbonyl)phenyl] oxalate (TDPO), were evaluated
      using the static system, and DNPO was found to have the most sensitive and stable
      chemiluminescence at a H(2)O(2) concentration of 30 mM. HPLC-chemiluminescence
      system using DNPO for the determination of estradiol was established. The
      detection limit of dansylated-estradiol (DNS-E2) was 15 fmol (4 pg) in the
      standard solution and 44 fmol (12 pg) in the rat plasma sample at S/N = 3.

PMID- 10960835
TI  - A high-performance liquid chromatography method using ultraviolet and
      fluorescence detection for the quantitation of UCN-01, 7-hydroxystaurosporine,
      from human plasma and saliva.
AB  - UCN-01, 7-hydroxystaurosporine, is an antagonist of protein kinase C, as well as
      causing cell cycle arrest. We developed and validated an HPLC assay method for
      the quantitation of UCN-01. Plasma and saliva standard curves were prepared at
      concentrations ranging from 0.2 to 20.0 microgram/mL and 4.0 to 200.0 ng/mL,
      respectively. The sample preparation consisted of acetonitrile precipitation.
      Separation was accomplished on a phenyl column and a C-18 precolumn insert
      utilizing a gradient-profile consisting of ammonium acetate and acetonitrile. UV
      detection was set at 295 nm for UCN-01 and 323 nm for umbelliferone, the internal
      standard. For fluorescence detection, excitation occurred at 290 nm, while
      emission was at 400 nm. The retention times were around 4 min for umbelliferone
      and 9.1 for UCN-01. Inter- and intra-assay errors of accuracy were less than 7.
      0% and 10.7%, respectively, for the plasma standard curve and less than 7.1% and
      6.7%, respectively, for the saliva standard curve. The recoveries of UCN-01 and
      umbelliferone from saliva were 81.4 +/- 0. 9% and 106.3 +/- 10.2%, respectively.
      The recovery of UCN-01 from plasma was 97.9 +/- 7.1% and for umbelliferone was
      103.3 +/- 2.3%. This method is suitable for quantifying UCN-01 in patient samples
      and further characterizing the clinical pharmacology of this compound. Published
      in 2000 by John Wiley & Sons, Ltd.

PMID- 10960836
TI  - Interaction of carbamazepine and phenobarbital in rabbits.
AB  - The interaction of carbamazepine and phenobarbital in rabbits was investigated.
      The drugs were administered to the rabbit orally as a single dose. By
      simultaneous administration the sequence of drugs was varied, with an interval
      between doses of 15 min. The doses of carbamazepine and phenobarbital were 100
      and 25 mg, respectively. It was established that phenobarbital appears to be an
      inductor for carbamazepine independently sequence of administration of the drugs.
      Carbamazepine reveals inductive properties for phenobarbital in the case where
      phenobarbital enteres in the organism first. It was ascertained also that, by
      simultaneous administration, these drugs reduce absorption of each other in
      plasma.

PMID- 10960837
TI  - Comparison of the activation status of tumor infiltrating and peripheral
      lymphocytes of patients with adenocarcinomas and benign hyperplasia of the
      prostate.
AB  - BACKGROUND: The presence of lymphocytic infiltration in prostate carcinomas has
      been shown to have prognostic relevance. However, it is not yet clear if this
      infiltrate represents a tumor-specific activated cell population or not.
      Therefore, the aim of the present study was to characterize the activation status
      of freshly isolated tumor infiltrating lymphocytes (TIL) from prostate carcinomas
      (PCa) and benign hyperplasia (BPH) with respect to the mRNA expression of
      cytokines and apoptotic factors. METHODS: TIL were isolated from mechanically
      disaggregated tumor material by gradient centrifugation. The cells of the
      interphase were depleted from epithelial cells with anti-human epithelial antigen
      magnetic beads and then CD3(+)- lymphocytes were selected with magnetic beads
      against this determinant. In these pure lymphocyte preparations the mRNA
      expression of IL-1, IL-10, IFN-gamma, TNF-alpha, Fas and Fas ligand was
      determined by using a semiquantitative RT-PCR. Contamination with tumor cells was
      excluded by a PCR for PSA and PSMA. RESULTS: The CD3(+)-TIL from 21 patients with
      PCa and 20 patients with BPH expressed significantly higher levels of IL-10- and
      Fas ligand-mRNA compared to the autologous CD3(+)- PBL, whereas the expression of
      IL-1-, TNF-alpha- and Fas-mRNA was not different in either cell population. In
      contrast, the mRNA levels of IFN-gamma were significantly higher only in the
      CD3(+)-TIL from the carcinomas but not from the BPH compared to autologous CD3(+)
      PBL. CONCLUSIONS: Since high levels of IFN-gamma have been reported to be
      produced by specifically lytic lymphocytes, our results suggest the presence of
      specifically activated TIL in the prostate carcinomas but not in the BPH, whereas
      inflammatory activated TIL are present both in the carcinomas and the BPH.

PMID- 10960838
TI  - The novel heterodinucleoside dimer 5-FdU-NOAC is a potent cytotoxic drug and a
      p53-independent inducer of apoptosis in the androgen-independent human prostate
      cancer cell lines PC-3 and DU-145.
AB  - BACKGROUND: We analyzed the cytotoxic properties of the new heterodinucleoside
      phosphate dimer 5-FdU-NOAC, which is composed of the cytotoxic drugs 5-FdU and
      N(4)-octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC) against human prostate
      tumor cells. METHODS: 5-FdU-NOAC effects on cell proliferation, cell cycle
      distribution, thymidylate synthase activity, and apoptosis were investigated in
      vitro in the two human prostate carcinoma cell lines DU-145 and PC-3 and compared
      to cells treated with the corresponding single drugs 5-FdU and NOAC. RESULTS:
      Treatment of the cells with 5-FdU-NOAC resulted in IC(50) values of 3.9-5 microM
      and in a complete inhibition of cell proliferation at 200 microM after 96 hr
      compared to 5-FdU, where 10% of the cells remained resistant. Flow cytometric
      analysis revealed cell cycle perturbations in S-phase only in the DU-145 cells. 5
      FdU-NOAC caused 50% inhibition of thymidylate synthase after 90 min at 0.6 microM
      in both cell lines. Apoptotic cell fractions in DU-145 (66%) and in PC-3 (34%)
      cells were found after treatment with 5-FdU-NOAC for 96 hr. DNA fragmentation
      further confirmed the induction of apoptosis. CONCLUSIONS: 5-FdU-NOAC inhibits
      thymidylate synthase and cell cycle progression causing proliferation arrest and
      apoptosis in DU-145 and PC-3 cells, suggesting a potential role of 5-FdU-NOAC for
      the treatment of prostate cancer.

PMID- 10960839
TI  - Evaluation of prostatic specific antigen and digital rectal examination as
      screening tests for prostate cancer.
AB  - BACKGROUND: The 11,811 first visits and 46,751 annual follow-up visits performed
      since 1988 were analyzed in order to assess the efficacy of serum prostatic
      specific antigen (PSA) and digital rectal examination (DRE) for diagnosis of
      prostate cancer. METHODS: At first visit, screening included DRE and measurement
      of PSA using 3.0 ng/ml as upper limit of normal, demonstrated as optimal value in
      the course of the study. Transrectal echography of the prostate (TRUS) was
      performed only if PSA and/or DRE was abnormal. For elevated PSA, biopsy was
      performed only if PSA was above the value predicted from prostatic volume
      measured by TRUS. At follow-up visits, it was decided during the course of the
      study to use PSA alone. RESULTS: PSA was above 3.0 ng/ml in 16.6% and 15.6% of
      men at first and follow-up visits, respectively. Prostate cancer was found in
      2.9% of men invited for screening at first visit and in only 0.4% of men at
      follow-up visits for a 7.1-fold decrease at follow-up visits done up to 11 years.
      PSA alone allowed to find 90.5% and 90. 0% of cancers at first and follow-up
      visits, respectively, compared to 41.1% and 25.0% by DRE alone. In the presence
      of normal PSA, 344 and 1,919 DREs are needed to find one prostate cancer at first
      and follow-up visits, respectively. A significant improvement in stage of the
      disease is found at follow-up (215 cancers) compared to first visits (337
      cancers). Comparison made between men invited for screening and those who were
      not invited but screened showed no significant difference in terms of incidence
      and prevalence of prostate cancer as well as diagnosis of cancer as a function of
      age or as a function of PSA, DRE, and TRUS data. The cost for finding one case of
      prostate cancer is estimated at Can $2,420 and Can $7, 105 (first and follow-up
      visits, respectively, when PSA is used as prescreening). CONCLUSIONS: PSA used as
      prescreening and followed by DRE and TRUS when PSA is abnormal is highly
      efficient in detecting prostate cancer at a localized (potentially curable) stage
      since 99% of the cancers diagnosed were at such a localized stage, thus
      practically eliminating the diagnosis of metastatic and noncurable prostate
      cancer. The approach used is highly reliable, sensitive, efficient, and
      acceptable by the general population. The detection of clinically nonsignificant
      cancer is an exception.

PMID- 10960840
TI  - Estrogen receptor gene expression and its relation to the estrogen-inducible
      HSP27 heat shock protein in hormone refractory prostate cancer.
AB  - BACKGROUND: The recent discovery of the classical estrogen receptor alpha
      (ERalpha) in androgen-insensitive prostate cancer has shed new light on the role
      of estrogens in endocrine therapy failure. To get more information on downstream
      events of estrogen signaling in these tumors, we investigated the relation
      between ERalpha gene expression, and the estrogen-inducible heat shock protein
      HSP27 in recurrent prostatic adenocarcinomas. METHODS: Palliative transurethral
      resection specimens from 50 patients with androgen-insensitive disease were
      submitted for study. Messenger RNA in situ hybridization for the ERalpha and
      immunohistochemistry of the HSP27 protein were performed on adjacent sections of
      an equal number of prostate cancer tissue with and without ERalpha protein
      expression. RESULTS: Cancerous lesions lacking the nuclear ERalpha at the protein
      level revealed ERalpha mRNA expression in 15 of 25 cases (60%). A coordinate
      expression of ERalpha mRNA and HSP27 was observed in 33 of 40 cases (83%),
      although a significant correlation between ERalpha protein and HSP27 expression
      was not obtained. Conversely, 90% of neoplastic lesions without detectable levels
      of ERalpha mRNA and protein also lacked HSP27 immunoreactivity. CONCLUSIONS:
      ERalpha gene expression at the mRNA level significantly correlated with the
      immunoprofile of the estrogen-inducible HSP27 protein in androgen-insensitive
      prostatic adenocarcinomas. This may indicate that these tumors harbor functional
      active estrogen receptors promoting transcriptional activity of the HSP27 gene.
      Determination of the receptor status by immunohistochemistry is unable to
      identify neoplastic lesions with established ERalpha mRNA expression in a
      substantial number of cases. HSP27 may be an additional surrogate biomarker for
      estrogen-regulated growth in androgen-insensitive prostate cancer.

PMID- 10960841
TI  - Vascular endothelial growth factor content in metastasizing and nonmetastasizing
      Dunning prostatic adenocarcinoma.
AB  - BACKGROUND: Tumor angiogenesis is important in progressive tumor growth and
      metastasis. In the normal rat prostate and in androgen-sensitive prostate tumors
      androgen ablation causes an involution of the vasculature and a decrease in the
      vascular endothelial growth factor (VEGF) levels before regression of the
      prostate gland. To examine whether angiogenesis and metastasis are regulated by
      VEGF in androgen-insensitive and metastasizing prostate tumors, five Dunning rat
      prostate cancer sublines were tested; the androgen-sensitive, nonmetastasizing
      R3327 PAP, and the androgen-insensitive, low metastasizing AT-1, and the three
      androgen-insensitive, metastasizing AT-2, AT-3, and MatLyLu Dunning prostatic
      adenocarcinomas. METHODS: VEGF levels were quantified in the rat dorsolateral
      prostate and in the five Dunning sublines using competitive RT-PCR, Western blot,
      and Elisa. Vascular density was determined by factor VIII staining. RESULTS: VEGF
      mRNA was increased in all tumors compared with normal prostates. The two
      metastatic sublines AT-3 and MatLyLu and the nonmetastatic subline AT-1 showed
      the highest VEGF mRNA expression. VEGF protein levels in the prostate gland
      showed increased expression in the metastatic sublines, AT-2, AT-3, and MatLyLu,
      compared with the nonmetastatic AT-1 subline and the ventral prostate. VEGF
      proteins in serum were highest in the metastatic AT-3 subline. The vessel density
      was highest in the two highly metastatic sublines AT-3 and MatLyLu. CONCLUSIONS:
      Our results suggest that VEGF levels are associated with microvessel density and
      the previously established metastatic pattern of these rat prostate tumor
      systems.

PMID- 10960842
TI  - Macrophage migration inhibitory factor in prostatic adenocarcinoma: correlation
      with tumor grading and combination endocrine treatment-related changes.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a ubiquitary cytokine
      whose expression has been investigated in tumors, showing a correlation between
      tumor aggressiveness and production of this protein by neoplastic cells. The aim
      of our study was to correlate MIF expression with tumor grade (Gleason scoring
      system) and histopathological changes after combined endocrine treatment (CET) of
      prostate adenocarcinoma. METHODS: We analyzed MIF immunoreactivity in 124 paired
      needle biopsies and radical prostatectomy specimens from 62 prostate cancer
      patients, of which 20 had been treated with CET. RESULTS: In untreated prostates,
      MIF expression significantly correlated with tumor grading, being stronger in low
      grade than in high-grade adenocarcinoma. In treated prostates, histopathological
      changes also correlated with MIF immunoreactivity, but not in a significant
      manner. CONCLUSIONS: The results of the current study demonstrated that with
      histological dedifferentiation, prostate adenocarcinoma cells show a reduced MIF
      expression. This finding may be the consequence of a reduced MIF synthesis or the
      result of an enhanced and altered secretion by tumor cells into the surrounding
      stroma. The consequent abnormal interaction between MIF and environmental factors
      might influence tumor growth and diffusion. On the other hand, the minor but not
      significantly reduced MIF expression by tumor cells after CET seems to exclude a
      hormonal regulation of MIF secretion.

PMID- 10960843
TI  - Heat-shock proteins inhibit induction of prostate cancer cell apoptosis.
AB  - BACKGROUND: Resistance to apoptosis remains a significant problem in the
      treatment of prostate cancer. Heat-shock proteins (HSP) have been correlated with
      tumor progression. The role of HSP in prostate cancer resistance to apoptosis is
      unknown. METHODS: PC-3 and LNCaP prostate cancer cells were heat-shocked and then
      treated with or without diethyl-maleate, etoposide, cycloheximide, or 3 Gray
      irradiation. Percent apoptosis was assessed by propidium iodide DNA
      incorporation. Protein was also extracted for analysis by SDS-PAGE Western
      blotting. RESULTS: Western blotting confirmed an increase in HSP 27 and 72. These
      cells were resistant to both chemical- and radiation-induced apoptosis.
      Cycloheximide and specific oligonucleotides to HSP 72 blocked the increased
      expression of HSP 72 and the resistance to apoptosis. Mcl-1, Bcl-2, Bcl-X(L), and
      glutathione-S-transferase (GST) expression were increased in a time-dependent
      manner after heat shock. CONCLUSIONS: This study demonstrates that HSP
      expression, specifically HSP 72, inhibits apoptosis in prostate tumor cell lines,
      which may be mediated by the production of survival factors.

PMID- 10960844
TI  - Early-onset hereditary prostate cancer is not associated with specific clinical
      and biological features.
AB  - BACKGROUND: Familial prostate cancer (CaP) accounts for 15-20% of all CaP, and
      hereditary CaP for 5-10% of patients. Few data are available concerning their
      clinical and biological features. METHODS: We compared diagnostic modalities,
      age, clinical stage, PSA, and tumor grade at diagnosis in CaP patients according
      to familial CaP profile: hereditary (HR) (> or =3 CaP), familial nonhereditary
      (FNH) (= 2 CaP), and sporadic CaP. Only cases diagnosed after January 1, 1987
      (PSA-available period) were included. We considered as informative sporadic (IS)
      cases those probands with 2+ nonaffected brothers at least 50 years old. Finally,
      267 CaP (230 probands and 37 affected brothers) were studied. RESULTS: In
      multivariate analysis, the only specific parameter significantly associated with
      HR and FNH CaP was early age at diagnosis; mean ages were 65.3 years (HR), 67
      years (FNH), and 70.9 years (IS) (P < 0. 0001). No significant difference was
      observed concerning clinical stage, PSA, and tumor grade. In addition, diagnostic
      modalities were similar in the three groups. CONCLUSIONS: Our data confirm the
      occurrence of early-onset CaP in hereditary families. Although the clinical and
      biological presentation of HR CaP remains controversial, the lack of specific
      features observed in our study leads us to conclude that there is no difference
      in the aggressiveness of the disease in hereditary compared to sporadic CaP.

PMID- 10960845
TI  - Vascular endothelial growth factor expression and capillary architecture in high
      grade PIN and prostate cancer in untreated and androgen-ablated patients.
AB  - BACKGROUND: Recent studies have demonstrated that angiogenesis is a potent
      prognostic indicator for patients with prostate cancer (PCa) and have pointed out
      that the evaluation of vascular endothelial growth factor (VEGF) is useful in
      assessing the angiogenic phenotype in PCa. The aim of the study was to
      investigate immunohistochemically the expression of VEGF and its correlation with
      the pattern of capillary architecture in prostate cancer and high-grade prostatic
      intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients.
      METHODS: Forty-five patients who underwent radical prostatectomy (RP) for
      localized prostate carcinoma were recruited for this study. The study population
      included two groups: 35 patients who did not receive chemo-, hormone, or
      radiation therapy before surgery, and 10 patients who were under complete
      androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by
      immunohistochemistry, and its tissue expression was compared with the pattern of
      capillary architecture evaluated by immunostaining the endothelial antigen CD34.
      The relationship of VEGF expression to chromogranin A-positive (e.g.,
      neuroendocrine) cells was investigated. RESULTS: In normal tissue, the intensity
      of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from
      negative to low. Very few basal cells stained for VEGF. All prostate cancer
      specimens stained positively, the intensity of the immunoreaction ranging from
      low to strong and being correlated with the Gleason score. Strongly positive VEGF
      immunoreactivity was detected in vascular endothelial cells and in stromal cells
      surrounding blood vessels. Two discrete immunostaining patterns were observed in
      high-grade PIN. VEGF expression of low-to-moderate intensity was defined as
      pattern A. The other, characterized by a strong cytoplasmic immunoreaction
      similar to that of poorly differentiated tumors, was defined as pattern B. The
      capillary architecture in high-grade PIN with pattern A was similar to the
      orderly vascular network seen in normal prostates, whereas in the pattern B it
      had the characteristics of microvessels usually seen in PCa. The degree of
      vascularization in the stroma adjacent to intensely VEGF-stained cells
      (neuroendocrine phenotype) was higher than that noted in association with
      secretory cells. CAB before surgery downregulated the expression of VEGF and
      decreased the degree of vascularization, except in the cell areas with
      neuroendocrine (NE) features. CONCLUSIONS: Our immunohistochemical results
      indicate that significant levels of VEGF are present in prostate cancer and in a
      population of PIN lesions, expression being highest in association with NE cells.
      VEGF expression is downregulated by hormonal manipulation, except in the
      population of NE cells.

PMID- 10960846
TI  - In vivo activity of a PSA-activated doxorubicin prodrug against PSA-producing
      human prostate cancer xenografts.
AB  - BACKGROUND: There is currently no effective therapy for men with metastatic
      prostate cancer who relapse after androgen ablation. Prolonged administration of
      effective concentrations of standard chemotherapeutic agents is usually not
      possible because of dose-limiting systemic toxicities. A new strategy to target
      cytotoxic agents specifically to sites of metastatic prostate cancer while
      avoiding systemic toxicity would be to develop prodrugs that are inactive when
      given systemically but become activated when processed proteolytically within
      prostate cancer metastases by prostate-specific antigen (PSA). In this study, the
      in vivo activity of a prodrug consisting of doxorubicin (Dox) conjugated to a PSA
      specific peptide carrier is described. METHODS: Nude mice bearing PSA-producing
      human prostate cancer xenografts were treated either intraperitoneally (IP) or by
      continuous infusion with the Dox prodrug. Toxicity (weight loss, death) and
      antitumor efficacy (tumor volume changes) were determined. RESULTS: The PSA
      peptide Dox prodrug had no discernible systemic toxicity when given at four times
      the 100% lethal Dox equivalent dose. An IP dose of 60 mg/kg/week x 4 weeks
      resulted in a 57% decrease in tumor weight vs. control after 40 days. A 25
      mg/kg/week dose given by continuous infusion produced a similar decrease in tumor
      weight vs. control. CONCLUSIONS: The PSA-specific peptide/doxorubicin prodrug can
      be used to deliver higher intratumoral levels of Dox for longer duration while
      avoiding systemic toxicity. In addition, these results validate the specificity
      of the PSA-specific peptide as a targetable drug carrier. This PSA-specific
      peptide could also be used as a carrier to target a wide variety of cytotoxic
      agents for specific activation within sites of metastatic prostate cancer.

PMID- 10960847
TI  - Preface.

PMID- 10960848
TI  - A classification of disease mapping methods.
AB  - This paper considers the underlying principles of depicting disease incidence on
      geographical maps and uses them to attempt a comparative classification of
      methods. After a discussion of the possibilities for incorporating time, we
      consider projection methods, some of which have been used to portray information
      in a manner supposed to be independent of population density. We then distinguish
      between non-parametric and model-based methods, including models for areal data
      using Bayesian ideas. Data in point form are also discussed and it is argued that
      the relative risk function provides a fundamental model useful for assessing
      different methods as a whole, some of which are known to be flawed and many of
      which are untested as regards their statistical properties.

PMID- 10960849
TI  - Disease mapping models: an empirical evaluation. Disease Mapping Collaborative
      Group.
AB  - The analysis of small area disease incidence has now developed to a degree where
      many methods have been proposed. However, there are few studies of the relative
      merits of the methods available. While many Bayesian models have been examined
      with respect to prior sensitivity, it is clear that wider comparisons of methods
      are largely missing from the literature. In this paper we present some
      preliminary results concerning the goodness-of-fit of a variety of disease
      mapping methods to simulated data for disease incidence derived from a range of
      models. These simulated models cover simple risk gradients to more complex true
      risk structures, including spatial correlation. The main general results
      presented here show that the gamma-Poisson exchangeable model and the Besag, York
      and Mollie (BYM) model are most robust across a range of diverse models. Mixture
      models are less robust. Non-parametric smoothing methods perform badly in
      general. Linear Bayes methods display behaviour similar to that of the gamma
      Poisson methods.

PMID- 10960850
TI  - Inference on a collapsed margin in disease mapping.
AB  - This paper describes a method for estimating the risk from a disease over a set
      of contiguous geographical regions, when data on a potentially important
      covariate, such as race, are not available. Conditions under which the extra
      margin can be recovered are suggested. An application to prostate cancer
      mortality among the non-white population in the counties of the U.S.A. is
      discussed.

PMID- 10960851
TI  - Exploring spatio-temporal patterns of mortality using mixed effects models.
AB  - A linear mixed effects (LME) model previously used for a spatial analysis of
      mortality data for a single time period is extended to include time trends and
      spatio-temporal interactions. This model includes functions of age and time
      period that can account for increasing and decreasing death rates over time and
      age, and a change-point of rates at a predetermined age. A geographic hierarchy
      is included that provides both regional and small area age-specific rate
      estimates, stabilizing rates based on small numbers of deaths by sharing
      information within a region. The proposed log-linear analysis of rates allows the
      use of commercially available software for parameter estimation, and provides an
      estimator of overdispersion directly as the residual variance. Because of
      concerns about the accuracy of small area rate estimates when there are many
      instances of no observed deaths, we consider potential sources of error, focusing
      particularly on the similarity of likelihood inferences using the LME model for
      rates as compared to an exact Poisson-normal mixed effects model for counts. The
      proposed LME model is applied to breast cancer deaths which occurred among white
      women during 1979-1996. For this example, application of diagnostics for
      multiparameter likelihood comparisons suggests a restriction of age to a minimum
      of either 25 or 35, depending on whether small area rate estimates are required.
      Investigation into a convergence problem led to the discovery that the changes in
      breast cancer geographic patterns over time are related more to urbanization than
      to region, as previously thought. Published in 2000 by John Wiley & Sons, Ltd.

PMID- 10960852
TI  - Comparing hierarchical models for spatio-temporally misaligned data using the
      deviance information criterion.
AB  - Bayes and empirical Bayes methods have proven effective in smoothing crude maps
      of disease risk, eliminating the instability of estimates in low-population areas
      while maintaining overall geographic trends and patterns. Recent work extends
      these methods to the analysis of areal data which are spatially misaligned, that
      is, involving variables (typically counts or rates) which are aggregated over
      differing sets of regional boundaries. The addition of a temporal aspect
      complicates matters further, since now the misalignment can arise either within a
      given time point, or across time points (as when the regional boundaries
      themselves evolve over time). Hierarchical Bayesian methods (implemented via
      modern Markov chain Monte Carlo computing methods) enable the fitting of such
      models, but a formal comparison of their fit is hampered by their large size and
      often improper prior specifications. In this paper, we accomplish this comparison
      using the deviance information criterion (DIC), a recently proposed
      generalization of the Akaike information criterion (AIC) designed for complex
      hierarchical model settings like ours. We investigate the use of the delta method
      for obtaining an approximate variance estimate for DIC, in order to attach
      significance to apparent differences between models. We illustrate our approach
      using a spatially misaligned data set relating a measure of traffic density to
      paediatric asthma hospitalizations in San Diego County, California.

PMID- 10960853
TI  - Identifiability and convergence issues for Markov chain Monte Carlo fitting of
      spatial models.
AB  - The marked increase in popularity of Bayesian methods in statistical practice
      over the last decade owes much to the simultaneous development of Markov chain
      Monte Carlo (MCMC) methods for the evaluation of requisite posterior
      distributions. However, along with this increase in computing power has come the
      temptation to fit models larger than the data can readily support, meaning that
      often the propriety of the posterior distributions for certain parameters depends
      on the propriety of the associated prior distributions. An important example
      arises in spatial modelling, wherein separate random effects for capturing
      unstructured heterogeneity and spatial clustering are of substantive interest,
      even though only their sum is well identified by the data. Increasing the
      informative content of the associated prior distributions offers an obvious
      remedy, but one that hampers parameter interpretability and may also
      significantly slow the convergence of the MCMC algorithm. In this paper we
      investigate the relationship among identifiability, Bayesian learning and MCMC
      convergence rates for a common class of spatial models, in order to provide
      guidance for prior selection and algorithm tuning. We are able to elucidate the
      key issues with relatively simple examples, and also illustrate the varying
      impacts of covariates, outliers and algorithm starting values on the resulting
      algorithms and posterior distributions.

PMID- 10960854
TI  - Triple-goal estimates for disease mapping.
AB  - Maps of regional morbidity and mortality rates play an important role in
      assessing environmental equity. They provide effective tools for identifying
      areas with potentially elevated risk, determining spatial trend, and formulating
      and validating aetiological hypotheses about disease. Bayes and empirical Bayes
      methods produce stable small-area rate estimates that retain geographic and
      demographic resolution. The beauty of the Bayesian approach lies in its ability
      to structure complicated models, inferential goals and analyses. Three
      inferential goals are relevant to disease mapping and risk assessment: (i)
      computing accurate estimates of disease rates in small geographic areas; (ii)
      estimating the distribution of disease rates over the region; (iii) ranking the
      disease rates so that environmental investigation can be prioritized. No single
      set of estimates can simultaneously optimize these three goals, and Shen and
      Louis propose a set of estimates that perform well on all three goals. These are
      optimal for estimating the distribution of rates and for ranking, and maintain a
      high accuracy in estimating area-specific rates. However, the Shen/Louis method
      is sensitive to choice of priors. To address this issue we introduce a
      robustified version of the method based on a smoothed non-parametric estimate of
      the prior. We evaluate the performance of this method through a simulation study,
      and illustrate it using a data set of county-specific lung cancer rates in Ohio.

PMID- 10960855
TI  - A method for quantifying artefacts in mapping methods illustrated by application
      to headbanging.
AB  - Maps of disease rates (and other quantities) often must contend with variance
      associated with variable population sizes and low incidence within spatial units.
      These characteristics can lead to substantial statistical noise that can mask
      underlying spatial variation. As Gelman and Price illustrated, most conventional
      mapping methods fail to address this problem, and in fact can introduce
      statistical artefacts; mapped quantities can show spatial patterns even when
      there are no spatial patterns in the underlying parameter of interest. Kafadar
      evaluated the performance of the headbanging algorithm for spatial smoothing
      (Tukey and Tukey, Hansen) for eliminating small scale variation and preserving
      edge structure. Here we perform a simulation study to investigate the artefacts
      of maps smoothed by unweighted and weighted headbanging. We find substantial
      artefacts that depend on the spatial structure of the statistical variation (for
      example, the spatial pattern of sample sizes) and on the details of the spatial
      distribution of geographic units. The methods used here could readily be adapted
      to study other spatial smoothers; we choose headbanging because (i) it is an
      important method used in practice, and (ii) its heavily computational nature is
      naturally studied using simulation (in contrast to the analytical methods used by
      Gelman and Price).

PMID- 10960856
TI  - Modelling spatial disease rates using maximum likelihood.
AB  - This paper concerns maximum likelihood estimation for a generalized linear mixed
      model (GLMM) useful for modelling spatial disease rates. The model allows for log
      linear covariate adjustment and local smoothing of rates through estimation of
      spatially correlated random effects. The covariance structure of the random
      effects is based on a recently proposed model which parameterizes spatial
      dependence through the inverse covariance matrix. A Markov chain Monte Carlo
      algorithm for performing maximum likelihood estimation for this model is
      described. Results of a computer simulation study that compared maximum
      likelihood (ML) and penalized quasi-likelihood (PQL) estimators are presented.
      Compared with PQL, ML produced less biased estimates of the intercept but the ML
      estimates were slightly more variable. Estimates of the other regression
      coefficients were unbiased and nearly identical for the two methods. ML
      estimators of the random effects standard deviation and spatial correlation were
      more biased than the corresponding PQL estimators. The conclusion is that ML
      estimators for GLMMs cannot be expected to perform better than PQL for small
      samples.

PMID- 10960857
TI  - Space-time mixture modelling of public health data.
AB  - This paper aims to enlarge the usual scope of disease mapping by means of dynamic
      mixtures (DMDM) in case a time component is involved in the data. A special
      mixture model is suggested which looks for space-time components (clusters)
      simultaneously. The idea is illustrated using data on female lung cancer from the
      East German cancer registry for 1960-1989. The conventional mixed Poisson
      regression model is used as a third model for comparison. The models are
      discussed in terms of their benefits, difficulties and ease in interpretation, as
      well as their statistical meaning. Some ideas on evaluation of these models are
      also included.

PMID- 10960858
TI  - Probabilistic small area risk assessment using GIS-based data: a case study on
      Finnish childhood diabetes. Geographic information systems.
AB  - A Bayesian hierarchical spatial model is constructed to describe the regional
      incidence of insulin dependent diabetes mellitus (IDDM) among the under 15-year
      olds in Finland. The model exploits aggregated pixel-wise locations for both the
      cases and the population at risk. Typically such data arise from combining
      geographic information systems (GIS) with large databases. The dates of diagnosis
      and locations of the cases are observed from 1987 to 1996. The population at risk
      counts are available for every second year during the same period. A hierarchical
      model is suggested for the pixel wise case counts, including a population model
      to account for the uncertainty of the population at risk over the years. The
      model is applied in the construction of disease maps (aggregated 100 km(2)
      pixels), and spatial posterior predictive distributions are computed to study
      whether there can be found a statistically exceptional number of cases in a small
      area of interest.

PMID- 10960859
TI  - Cluster modelling of disease incidence via RJMCMC methods: a comparative
      evaluation. Reversible jump Markov chain Monte Carlo.
AB  - The spatial modelling of small area health data has, for some time, included
      spatial autocorrelation as a random effect. This effect is non-specific and
      global and does not address the location of clusters of disease (a specific
      task). This paper addresses the need for specific and non-specific random effects
      within spatial epidemiology. In addition, individual frailty is also considered
      important and a computational algorithm based on reversible jump Markov chain
      Monte Carlo (RJMCMC) methods is described.

PMID- 10960860
TI  - Posterior predictive model checks for disease mapping models.
AB  - Disease incidence or disease mortality rates for small areas are often displayed
      on maps. Maps of raw rates, disease counts divided by the total population at
      risk, have been criticized as unreliable due to non-constant variance associated
      with heterogeneity in base population size. This has led to the use of model
      based Bayes or empirical Bayes point estimates for map creation. Because the maps
      have important epidemiological and political consequences, for example, they are
      often used to identify small areas with unusually high or low unexplained risk,
      it is important that the assumptions of the underlying models be scrutinized. We
      review the use of posterior predictive model checks, which compare features of
      the observed data to the same features of replicate data generated under the
      model, for assessing model fitness. One crucial issue is whether extrema are
      potentially important epidemiological findings or merely evidence of poor model
      fit. We propose the use of the cross-validation posterior predictive
      distribution, obtained by reanalyzing the data without a suspect small area, as a
      method for assessing whether the observed count in the area is consistent with
      the model. Because it may not be feasible to actually reanalyze the data for each
      suspect small area in large data sets, two methods for approximating the cross
      validation posterior predictive distribution are described.

PMID- 10960861
TI  - Evaluation of spatial filters to create smoothed maps of health data.
AB  - Spatial filters have been used as an easy and intuitive way to create smoothed
      disease maps. Birth weight data from New York State for 1994 and 1995 are used to
      compare the traditional filter type of fixed geographical size with a filter size
      of constant or nearly constant population size. The latter are more appropriate
      for mapping disease in geographic areas with widely varying population density,
      such as New York State. Issues such as the choice of population size for the
      filter, the scale of smoothing, the ability to detect true spatial variation and
      the ability to smooth over random spatial noise are evaluated and discussed.

PMID- 10960862
TI  - An empirical evaluation of various priors in the empirical Bayes estimation of
      small area disease risks.
AB  - Empirical and fully Bayes estimation of small area disease risks places a prior
      distribution on area-specific risks. Several forms of priors have been used for
      this purpose including gamma, log-normal and non-parametric priors. Spatial
      correlation among area-specific risks can be incorporated in log-normal priors
      using Gaussian Markov random fields or other models of spatial dependence.
      However, the criterion for choosing one prior over others has been mostly logical
      reasoning. In this paper, we evaluate empirically the various priors used in the
      empirical Bayes estimation of small area disease risks. We utilize a Spanish
      mortality data set of a 12-year period to give the underlying true risks, and
      estimate the true risks using only a 3-year portion of the data set. Empirical
      Bayes estimates are shown to have substantially smaller mean squared errors than
      Poisson likelihood-based estimates. However, relative performances of various
      priors differ across a variety of mortality outcomes considered. In general, the
      non-parametric prior provides good estimates for lower-risk areas, while spatial
      priors provide good estimates for higher-risk areas. Ad hoc composite estimates
      averaging the estimates from the non-parametric prior and those from a spatial
      log-normal prior appear to perform well overall. This suggests that an empirical
      Bayes prior that strikes a balance between these two priors, if one can construct
      such a prior, may prove to be useful for the estimation of small area disease
      risks.

PMID- 10960863
TI  - Parametric bootstrap and penalized quasi-likelihood inference in conditional
      autoregressive models.
AB  - This paper discusses a variety of conditional autoregressive (CAR) models for
      mapping disease rates, beyond the usual first-order intrinsic CAR model. We
      illustrate the utility and scope of such models for handling different types of
      data structures. To encourage their routine use for map production at statistical
      and health agencies, a simple algorithm for fitting such models is presented.
      This is derived from penalized quasi-likelihood (PQL) inference which uses an
      analogue of best-linear unbiased estimation for the regional risk ratios and
      restricted maximum likelihood for the variance components. We offer the
      practitioner here the use of the parametric bootstrap for inference. It is more
      reliable than standard maximum likelihood asymptotics for inference purposes
      since relevant hypotheses for the mapping of rates lie on the boundary of the
      parameter space. We illustrate the parametric bootstrap test of the practically
      relevant and important simplifying hypothesis that there is no spatial
      autocorrelation. Although the parametric bootstrap requires computational effort,
      it is straightforward to implement and offers a wealth of information relating to
      the estimators and their properties. The proposed methodology is illustrated by
      analysing infant mortality in the province of British Columbia in Canada.

PMID- 10960864
TI  - Methodological issues in the development of the Canadian Cancer Incidence Atlas.
AB  - The Canadian Cancer Incidence Atlas is among recent national atlases using
      incidence rather than mortality data. Methods used to assess the significance and
      spatial correlation of the age-standardized rates (ASIRs) for the 290 census
      divisions are described. The expected number of cases by area was used to
      determine cancer sites with sufficient cases to be mapped. ASIR significance was
      assessed using a simulation based on a Poisson distribution. The consistency of
      the observed case distributions with the Poisson distribution was examined. The
      bootstrap confidence interval (CI) for the ASIR developed by Swift was used in
      the atlas. Spatial correlation was assessed with Moran's I/I(max) and the
      significance determined by a simulation in order to allow for area population
      variation. Data quality indicators typically used for cancer registries were
      presented, supplemented by a registry questionnaire.

PMID- 10960865
TI  - Spatial competing risk models in disease mapping.
AB  - Often it is required that the 'health status' of an area must be assessed and
      this involves the analysis of a range of different diseases within one study
      window. This often arises, for example, when disease cluster alarms are sounded
      and there is a need to provide a general overview of health in the vicinity of he
      cluster area. Our approach leads to the consideration of the joint spatial
      distribution of a 'basket' of diseases. We examine the use of weighting schemes
      within our general formulation, and extensions to count data and spatio-temporal
      modelling.

PMID- 10960866
TI  - Multivariate spatial models for event data.
AB  - This paper describes how estimates made for event rates in small areas may be
      enhanced through spatial modelling of the data - taking the geographical location
      of each area into account - and through the addition of further information from
      each area. In particular we consider the use of spatial models to predict more
      than one outcome simultaneously. This is done by writing the spatial model as a
      multi-level model and subsequently enhancing this to encompass a multivariate
      data structure; estimates are obtained using iterative generalized least squares
      in the software package MLwiN. The example given considers mortality due to two
      causes--neoplasms and circulatory disease--in 143 postcode sectors in Greater
      Glasgow Health Board, Scotland. In addition, a measure of socio-economic
      deprivation is available for each area. Correlations between causes within areas,
      between areas within causes and between areas and causes are quantified, as are
      the relative contributions of the heterogeneous and spatial parts of the model.
      The results suggest a tendency for there to be pockets with high mortality rates
      due to neoplasms, whilst mortality due to circulatory disease follows a much
      smoother pattern. After taking deprivation into account, the spatial component
      accounts for just 19 per cent of the variation in the mortality due to neoplasms
      in Greater Glasgow but 66 per cent of the mortality due to circulatory disease.

PMID- 10960867
TI  - Multiregion contact systems for modelling STD epidemics.
AB  - This paper elicits properties of some multiregional contact systems for STD
      infections that are intended to assist the understanding of disease control
      strategies. To this end, a space-time SIS model is described that maintains the
      symmetry of contact that is inherent in the formation of sexual partnerships. It
      is demonstrated how the characteristic stability conditions of this model provide
      a framework for understanding the potential for sustained transmission after the
      introduction of the agent into a given region. Then, more complex SI
      specifications are derived that are particularly relevant to the transmission of
      HIV. These extensions include the introduction of alternative modes of travel and
      behavioural adaptations made in response to the circulation of HIV and the
      incidence of AIDS. The discussion suggests some additions to the systems that
      might enhance their applicability in practice.

PMID- 10960868
TI  - Statistical issues in the analysis of disease mapping data.
AB  - In this paper we discuss a number of issues that are pertinent to the analysis of
      disease mapping data. As an illustrative example we consider the mapping of
      larynx cancer across electoral wards in the North West Thames region of the U.K.
      Bayesian hierarchical models are now frequently employed to carry out such
      mapping. In a typical situation, a three-stage hierarchical model is specified in
      which the data are modelled as a function of area-specific relative risks at
      stage one; the collection of relative risks across the study region are modelled
      at stage two; and at stage three prior distributions are assigned to parameters
      of the stage two distribution. Such models allow area-specific disease relative
      risks to be 'smoothed' towards global and/or local mean levels across the study
      region. However, these models contain many structural and functional assumptions
      at different levels of the hierarchy; we aim to discuss some of these assumptions
      and illustrate their sensitivity. When relative risks are the endpoint of
      interest, it is common practice to assume that, for each of the age-sex strata of
      a particular area, there is a common multiplier (the relative risk) acting upon
      each of the stratum-specific risks in that area; we will examine this
      proportionality assumption. We also consider the choices of models and priors at
      stages two and three of the hierarchy, the effect of outlying areas, and an
      assessment of the level of smoothing that is being carried out. For inference, we
      concentrate on the description of the spatial variability in relative risks and
      on the association between the relative risks of larynx cancer and an area-level
      measure of socio-economic status.

PMID- 10960869
TI  - Two new templates for epidemiology applications: linked micromap plots and
      conditioned choropleth maps.
AB  - This paper describes two interactive templates for representing spatially indexed
      estimates. Both templates use a matrix layout of small panels. The first
      template, called linked micromap plots, can represent multivariate estimates
      associated with each spatially indexed study unit. The second template, called
      conditioned choropleth maps, shows the connection between a dependent variable,
      as represented in a classed choropleth map, and two explanatory variables. The
      paper describes the cognitive considerations that motivate the layouts and
      representation details. The discussion also addresses topics of data quality and
      access, hypothesis generation, and interactive features such as pan and zoom and
      dynamic conditioning via sliders. The examples show epidemiological (mortality
      rates) and environmental (toxic concentrations) applications.

PMID- 10960870
TI  - Non-parametric maximum likelihood estimators for disease mapping.
AB  - A Non-Parametric Maximum Likelihood approach to the estimation of relative risks
      in the context of disease mapping is discussed and a NPML approximation to
      conditional autoregressive models is proposed. NPML estimates have been compared
      to other proposed solutions (Maximum Likelihood via Monte Carlo Scoring,
      Hierarchical Bayesian models) using real examples. Overall, the NPML
      autoregressive estimates (with weighted term) were closer to the Bayesian
      estimates. The exchangeable NPML model ranked immediately after, even if it
      implied a greater shrinkage, while the truncated auto-Poisson showed inadequate
      for disease mapping. The coefficients of the autoregressive term for the
      different mixtures have clear interpretations: in the breast cancer example, the
      larger cities in the region showed high rates and very low correlation with the
      neighbouring areas, while the less populated rural areas with low rates were
      strongly positively correlated each other. This pattern is expected since breast
      cancer is strongly correlated with parity and age at first birth, and the female
      population of the rural areas experienced a decline in fertility much later than
      those living in the larger cities. The leukemia example highlighted the failure
      of the Poisson-Gamma model and other general overdispersion tests to detect high
      risk areas under specific conditions. The NPML approach in Aitkin is very
      general, simple and flexible. However the user should be warned against the
      possibility of local maxima and the difficulty in detecting the optimal number of
      components. Special software (such as CAMAN or DismapWin) had been developed and
      should be recommended mainly to not experienced users.

PMID- 10960871
TI  - Bayesian modelling of inseparable space-time variation in disease risk.
AB  - This paper proposes a unified framework for a Bayesian analysis of incidence or
      mortality data in space and time. We introduce four different types of prior
      distributions for space x time interaction in extension of a model with only main
      effects. Each type implies a certain degree of prior dependence for the
      interaction parameters, and corresponds to the product of one of the two spatial
      with one of the two temporal main effects. The methodology is illustrated by an
      analysis of Ohio lung cancer data 1968-1988 via Markov chain Monte Carlo
      simulation. We compare the fit and the complexity of several models with
      different types of interaction by means of quantities related to the posterior
      deviance. Our results confirm an epidemiological hypothesis about the temporal
      development of the association between urbanization and risk factors for cancer.

PMID- 10960872
TI  - Assessing health impact of environmental pollution sources using space-time
      models.
AB  - We used disease mapping for health impact assessment of the national airport of
      the Netherlands. Spatio-temporal models were used to relate hospital discharge
      data for acute myocardial infarction and bronchitis in 1991, 1992 and 1993 to
      noise and distance from the airport. To compare models a discrepancy measure
      (expected predictive deviance) proposed by Carlin and Louis was used. The best
      fitting model was the most general one with inclusion of spatial and temporal
      components. Results on the effects of the covariates noise and distance from the
      airport were somewhat inconsistent between men and women and between the two
      diseases: for women no association between bronchitis and distance from the
      airport was found, whereas for men no association between acute myocardial
      infarction and noise was found.

PMID- 10960873
TI  - Modelling categorical covariates in Bayesian disease mapping by partition
      structures.
AB  - We consider the problem of mapping the risk from a disease using a series of
      regional counts of observed and expected cases, and information on potential risk
      factors. To analyse this problem from a Bayesian viewpoint, we propose a
      methodology which extends a spatial partition model by including categorical
      covariate information. Such an extension allows detection of clusters in the
      residual variation, reflecting further, possibly unobserved, covariates. The
      methodology is implemented by means of reversible jump Markov chain Monte Carlo
      sampling. An application is presented in order to illustrate and compare our
      proposed extensions with a purely spatial partition model. Here we analyse a well
      known data set on lip cancer incidence in Scotland.

PMID- 10960874
TI  - Waldenstrom's macroglobulinaemia: laboratory diagnosis and treatment.

PMID- 10960875
TI  - Effects of cyclic polylactate (CPL) on the growth of cloned leukemic cells in
      vitro.
AB  - A novel supramolecular oligomer, cyclic polylactate (CPL), was first discovered
      in the culture medium of HeLa-S tumour cells, and was reported to inhibit the
      growth of FM3A ascites tumour cells by inhibiting the activities of pyruvate
      kinase (PK) and lactic dehydrogenase (LDH). We have now synthesized CPL
      containing oligomers with polymerization numbers ranging from 9 to 19, by
      prolonged heating and rapid mixing of a carbohydrate compound of the L-lactic
      acid monomer (C(3)H(6)O(3)) under decreased pressure and have studied its effects
      on the growth of leukemic cells. Treatment with 0.02 mg/ml CPL inhibited the
      growth of HL60 and TF-1 cells, while the growth of K562 cells was inhibited by
      0.2 mg/ml CPL. A concentration of 2 mg/ml CPL was required to inhibit granulocyte
      macrophage progenitor cell (CFU-GM) and burst-forming unit erythroid (BFU-E)
      precursor colony formation among normal bone marrow cells. Furthermore, 7A6
      antigen expression and DNA ladder formation were observed in leukemic cells
      cultured with CPL, indicating that CPL induces apoptotic changes in these cells.
      These findings suggest that CPL might be a useful chemotherapeutic agent for
      leukemia.

PMID- 10960877
TI  - Recent publications in hematological oncology.

PMID- 10960876
TI  - Prognostic models for diffuse large B-cell lymphoma.
AB  - Prognosis of DLCL patients is variable and associated with well-defined risk
      factors. In the past decade several pretreatment variables have been incorporated
      into prognostic models to predict the death risk of individual patients. The
      International Prognostic Index (IPI), developed in an international consensus
      study, has been one of the most widely accepted of these models. In our study we
      applied some of the major prognostic models proposed for DLCLs in a cohort of 111
      patients uniformly treated with a CHOP-like regimen in order to compare their
      sensitivity and specificity. We also evaluated the possibility of improving the
      IPI with the inclusion, from among the variables analysed, of serum beta-2
      microglobulin level (beta-2M). The sensitivity, reflecting the ability to predict
      all failures in the cohort of patients as a whole, has improved from 45 to 73 per
      cent when the beta-2M-IPI model is compared with IPI, without a significant loss
      of specificity. Based on these results, the beta-2M-IPI may be useful for
      identifying the subset of patients with very poor prognoses. Therefore, the use
      of the serum beta-2M value in addition to the IPI may help in selection of the
      patients with DLCL at higher risk for treatment failure, and identification of
      those who may require specifically tailored therapeutic approaches.

PMID- 10960878
TI  - Current awareness
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 geriatric psychiatry. Each bibliography is divided into 9 sections: 1 Books,
      Reviews & Symposia; 2 General; 3 Assessment; 4 Epidemiology; 5 Therapy; 6 Care; 7
      Dementia; 8 Depression; 9 Psychology. 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- 10960879
TI  - Validity of the serial seven procedure.
AB  - Serial subtraction by seven (Serial Seven Test, SST) is frequently used in mental
      status evaluation for dementia as a measure of concentration. Validation research
      on the SST has been limited. The literature to date raises significant concern
      about the nature of the procedure. The purpose of the present study was to
      evaluate the nature and validity of the SST. The participants were 80 consecutive
      outpatient referrals to the neuropsychology consultation service of two large
      general medical hospitals. All subjects were administered a comprehensive
      neuropsychological assessment battery, including the Mini Mental State
      Examination version of the SST. Multiple regression analysis indicated that
      calculation skill is at least as important as concentration, in predicting SST
      performance. Measures of overall level of cognitive dysfunction, education, and
      psychopathology were unrelated to SST performance. The results suggest that SST
      performance is heavily influenced by basic arithmetic skill and that the
      procedure should be used with caution as a measure of concentration or other
      nonacademic mental abilities.

PMID- 10960880
TI  - The Caregiver Activity Survey (CAS): longitudinal validation of an instrument
      that measures time spent caregiving for individuals with Alzheimer's disease.
AB  - Family members incur substantial financial costs during the course of caring for
      an individual with Alzheimer's disease. Much of this cost is associated with time
      spent in caregiving tasks, including supervision and communication with the
      patient, and assisting with activities of daily living. We have previously
      reported on the cross sectional reliability and validity of a scale that measures
      time spent caregiving, the Caregiver Activity Survey (CAS). This study extends
      our results to a longitudinal study of the validity of the instrument. Forty-four
      outpatients with Alzheimer's disease who lived with a primary caregiver were
      followed over a period of 1 year 6 months. At six month intervals, the patients
      were administered the Mini Mental State Exam (MMSE), Alzheimer's Disease
      Assessment Scale (ADAS), and the Physical Self Maintenance Scale (PSMS).
      Caregivers completed the CAS. Over time, the CAS correlated significantly with
      the MMSE (r=-0.58, p=0.000), ADAS cognitive subscale (r=0.56, p=0. 000) and PSMS
      (r=0.49, p=0.000). As patients declined, caregivers spent less time communicating
      with and more time supervising the patient. Excluding the communication item,
      time spent caregiving increased significantly over time. This prospective study
      longitudinally validates the CAS with Alzheimer's patients.

PMID- 10960881
TI  - The effectiveness of old age psychiatry services.
AB  - The objective of this study was to review outcomes of acute service delivery in
      old age psychiatry. Sources of data included Medline, PsycINFO and Cochrane
      Collaboration databases of English language papers to 1998 on service delivery
      evaluation in 'old age psychiatry', 'psychogeriatrics' and 'geriatric
      psychiatry', supplemented by a manual search of references from relevant
      literature. All controlled trials, audits, and surveys of the outcomes of service
      delivery in old age psychiatry located in acute hospitals and community settings
      were included. Service delivery by medical, adult psychiatry and
      consultation/liaison services were included. With the exception of outreach
      services to nursing homes, long term institutional care was excluded. All data
      were extracted by the author. Data quality was assessed by applying an evidence
      hierarchy. Evaluation strategies were qualitatively reviewed. Controlled trials,
      audits and surveys were each found to provide important data in the evaluation of
      service delivery. There is better quality evidence to support the effectiveness
      of components of old age psychiatry services than other service types. The
      majority of studies indicate that old age psychiatry services have positive acute
      treatment outcomes, particularly with depression. There is insufficient evidence
      to determine which processes of care are associated with better outcomes.
      Pluralistic evaluations indicate that carers often have unmet needs and are not
      as positive about outcomes. There have been no controlled comparisons of service
      delivery provided by other services. In conclusion, controlled trials and audits
      indicate that old age psychiatry services are effective. Further pluralistic
      evaluations and comparisons with other services are required.

PMID- 10960883
TI  - Donepezil in Alzheimer's disease: eighteen month results from Southampton Memory
      Clinic.
AB  - The objective of this study was to assess the efficacy of donepezil in patients
      with mild to moderate Alzheimer's disease (AD) in clinical practice. This was an
      open-label study in which patients were referred to an elderly mental health
      clinic in Southampton, UK. Eighty patients with mild to moderate AD received 5
      mg/day donepezil for the first 4 weeks, after which, if tolerated, the dose was
      increased to 10 mg/day. Efficacy and safety assessments were carried out every 3
      months. Efficacy was assessed by the Alzheimer's Disease Assessment Scale
      cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE),
      Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-carer Distress Scale
      (NPI-D). Mean improvements from baseline were observed at the 3-month assessment
      on all four efficacy measures. At 3 months, 39% of patients showed an improvement
      of at least 4 points on the ADAS-cog, and 37% of patients had improved by 4
      points or more on the NPI. In those patients who showed improvement and were
      maintained on donepezil, improvements were sustained for 18 months on the MMSE
      and NPI, 15 months on the NPI-D, and for 6 months on the ADAS-cog. Six per cent
      of patients discontinued medication due to adverse events. In a typical clinical
      practice setting, patients with mild to moderate AD tolerated donepezil well.
      Clinically meaningful improvements in cognitive function and a reduction in
      neuropsychiatric symptoms were demonstrated in nearly 40% of patients with
      associated reduction in carer distress. Continued benefit was seen for up to 18
      months in the selected group of patients who initially responded in treatment.

PMID- 10960882
TI  - Zaleplon shortens subjective sleep latency and improves subjective sleep quality
      in elderly patients with insomnia. The Zaleplon Clinical Investigator Study
      Group.
AB  - Insomnia is a frequent complaint in the elderly population. Hypnotic agents,
      including benzodiazepines, with longer pharmacological half-lives have been
      associated with side effects, including residual sedation, memory impairment, and
      discontinuation effects. Zaleplon is a short-acting (elimination half-life of 1
      hour), non-benzodiazepine hypnotic that acts on the benzodiazepine type 1 site of
      the gamma-aminobutyric acid type A (GABA(A)) receptor complex. The pharmacology
      and pharmacokinetics of Zaleplon suggest a safety profile that is improved over
      other hypnotics. The objective of this placebo-controlled study was to evaluate
      the efficacy and safety of Zaleplon (5 and 10 mg) in elderly (> or =65 years)
      outpatients with primary insomnia. This was a multicenter, double-blind,
      randomised, placebo-controlled 2-week outpatient study. Postsleep questionnaires
      were used to record subjective sleep variables: sleep latency, sleep duration,
      number of awakenings, and sleep quality. Zaleplon significantly reduced
      subjective sleep latency during both weeks of the study with both 5- and 10-mg
      doses. Subjective sleep quality was improved for significantly more patients
      treated with zaleplon 10 mg than those treated with placebo during both weeks of
      treatment. There was a weak indication of rebound insomnia after discontinuation
      of treatment with the 10-mg dose, but no significant difference in common
      treatment-emergent adverse events across treatment groups. Zaleplon is an
      effective and safe hypnotic for the treatment of insomnia in the elderly.

PMID- 10960884
TI  - Psychiatric assessment wards for older adults: a qualitative evaluation of two
      ward models.
AB  - This study was requested to investigate the relative strengths of two different
      ward arrangements. Both wards were psychiatric assessment wards for people over
      the age of 65 and both were mixed sex wards. The major focus was to examine if
      the separation of cognitively impaired (CI) and functional clients on an elderly
      assessment ward had benefits in terms of client and staff satisfaction. The study
      involved 192 hours of observation, following four clients on each ward for 24
      hours. Results indicate that the split ward and the mixed ward differ
      qualitatively and that in terms of user and staff satisfaction the split model is
      preferable. Implications for service development and future research are also
      discussed.

PMID- 10960885
TI  - The benefits and risks of ECT for patients with primary dementia who also suffer
      from depression.
AB  - BACKGROUND: Major depression afflicts 20-25% of patients with dementia. Of these,
      about a third do not improve with antidepressant therapy and may be suitable
      candidates for electronconvulsive treatment (ECT). However, the use of ECT is
      dementia patients is concerning due to possible adverse effects on memory and
      cognition. Outcome studies of ECT in patients with primary dementia and
      depression are very rare. OBJECTIVE: To determine the effectiveness and
      complications of ECT treatment for depression in dementia. METHOD: A chart review
      was conducted of all 31 patients wit ha discharge diagnosis of 'Dementia with
      depression' treated with ECT at the Johns Hopkins Hospital, over a five-year
      period. Admission and discharge ratings were made on the Mini-Mental State
      Examination (MMSE) and the Montgomery-Asberg Depression Rating Scale (MADRS) as
      part of the clinical routine. RESULTS: All patients suffered from dementia: 55%
      had vascular dementia, 13% Alzheimer's disease, and 32% degenerative dementia of
      uncertain etiology. The admission MADRS mean score was 27.5 (SD 8.1) and the MMSE
      mean score was 18.8 (SD 5. 5). The patients received between 1 and 23 ECT
      treatments (mean 9, SD 5.7). At discharge, there was a statistically significant
      mean decline on the MADRS of 12.28 points (p<0.01). Forty percent had scores less
      than 10 (normal) on the MADRS. While 49% of patients developed delirium, by
      discharge there was also a significant mean increase (improvement) in MMSE of
      1.62 points (p<0.02). CONCLUSIONS: ECT is an effective treatment for depression
      in dementia, leading to improvements in both mood and cognition. Multiple ECT
      treatments may be necessary before a significant improvement in mode is achieved.

PMID- 10960886
TI  - Suicide in older people: mode of death, demographic factors, and medical contact
      before death.
AB  - OBJECTIVE: To determine the demographic characteristics, mode of death, and
      nature and timing of medical contacts in the year before death in a sample of
      suicides in older people. DESIGN: Descriptive study of a case series of 195
      suicides in older people. SETTING: Four counties and one large urban area in
      central England, UK. SUBJECTS: Individuals 60 years old and over at time of
      death, who had died between 1 January 1995 and 1 May 1998, and whose deaths has
      received a coroner's verdict of suicide, or an open or accidental verdict where
      the circumstances of death indicated probable suicide. MAIN OUTCOME MEASUREMENTS:
      Demographic details and information on mode of death and medical contact prior to
      death derived from coroners' inquest notes, General Practitioners' (GP) case
      notes and psychiatric records. MAIN RESULTS: 67.7% were male. A higher proportion
      of men than women were single or divorced. The commonest methods of suicide were
      hanging in men and drug overdose in women, 49.8% had seen their GP in the month
      before death, although over half these last consultations were for physical
      complaints. Only 15.4% were under psychiatric care at the time of death.
      CONCLUSIONS: Older men are at higher risk of suicide than women. Given the high
      proportion of drug overdoses in the sample, effective strategies to prevent
      suicide in older people might include improving the prescribing of analgesics and
      antidepressants. Although older people at risk of suicide often consult their GP
      shortly before death, GPs may have difficulty identifying those at risk because
      of the high proportion of physical complaints.

PMID- 10960888
TI  - Psychiatry of the elderly: the WPA/WHO consensus statements.

PMID- 10960887
TI  - Priorities in dementia services: the interaction of purchasers and providers.

PMID- 10960889
TI  - Population aspects of the dementias.
AB  - In the United Kingdom there are some key facts which have implications for
      policies and services for people with dementia. The first group are to do with
      older people and their position in the total population. Overall the population
      of this country is projected to increase, but only by 0.2%. However, within that
      the population is ageing, i.e. the proportion of older people in the population
      is projected to increase and the proportion of very old people in the older
      population is also projected to increase. Also of significance is that the
      population of working age is projected to decline. Second gender and marital
      status are important variables. Third is the need to consider where people live.
      The two important facts here are that the proportion of people living alone is
      increasing, and expected to grow further, and family patterns are changing. Both
      of these will have an effect on who is available to care. But we also need to
      look at the implications of population change in the EU which have implications
      for the UK. Some of the implications and issues of these population aspects are
      then discussed.

PMID- 10960890
TI  - What help do GPs want from specialist services in managing patients with
      dementia?
AB  - The views of GPs about psychiatric services for dementia were obtained by
      questionnaire survey. Provision of adequate long term care, together with support
      for both family carers and healthcare workers were strongly stated needs. Other
      needs were rapid access to care, clear diagnosis, special needs of young patients
      with Alzheimer's disease, joint guidelines, and an increased role for CPNs. GPs
      valued the role of voluntary organisations and help given to them by Consultant
      Psycho-geriatricians.

PMID- 10960891
TI  - An old age psychiatrist at the Department of Health.

PMID- 10960892
TI  - Dementia and the law in England and Wales.

PMID- 10960894
TI  - Use of small scale bioassays in the discovery of novel drugs from natural
      sources.

PMID- 10960893
TI  - Naturally occurring antinociceptive substances from plants.
AB  - Despite the progress that has occurred in recent years in the development of
      therapy, there is still a need for effective and potent analgesics, especially
      for the treatment of chronic pain. One of the most important analgesic drugs
      employed in clinical practice today continues to be the alkaloid morphine. In
      this review, emphasis will be given to the important contribution and the history
      of Papaver somniferum, Salix species, Capsicum species and Cannabis sativa in the
      development of new analgesics and their importance in the understanding of the
      complex pathways related to electrophysiological and molecular mechanisms
      associated with pain transmission. Recently discovered antinociceptive substances
      include alkaloids, terpenoids and flavonoid. Plant-derived substances have, and
      will certainly continue to have, a relevant place in the process of drug
      discovery, particularly in the development of new analgesic drugs.

PMID- 10960895
TI  - Evaluation of the in vitro antioxidant activity of Mangifera indica L. extract
      (Vimang).
AB  - An extract of Mangifera indica L. (Vimang) was tested in vitro for its
      antioxidant activity using commonly accepted assays. It showed a powerful
      scavenger activity of hydroxyl radicals and hypochlorous acid and acted as an
      iron chelator. The extract also showed a significant inhibitory effect on the
      peroxidation of rat-brain phospholipid and inhibited DNA damage by bleomycin or
      copper-phenanthroline systems.

PMID- 10960896
TI  - Effects of extracts from flowering tops of Crataegus meyeri A. Pojark. on
      ischaemic arrhythmias in anaesthetized rats.
AB  - Different species of Crataegus, commonly called Hawthorn, were reported to
      possess wide pharmacological effects on the cardiovascular system. In the present
      study, chloroform, ethylacetate and methanol (70%) extracts of the flowering tops
      of Crataegus meyeri A. Pojark. were studied. The extracts were tested on the
      incidence and severity of arrhythmias induced by a period of myocardial ischaemia
      in open-chest anaesthetized male Wistar rats. Infusion of a hydroalcohol extract
      (1 mg/kg/min) resulted in a significant decrease in the total number of
      ventricular ectopic beats (from 1494 +/- 362 in the control to 634 +/- 102),
      mainly by reduction of beats occurring as ventricular tachycardia. A chloroform
      extract (1 mg/kg/min) also reduced the total number of ventricular ectopic beats
      but this reduction was due to the decrease of single extrasystoles. A significant
      reduction in the time spent for ventricular fibrillation was seen by the
      hydroalcohol and ethylacetate extracts. There were no significant changes in the
      heart rate and blood pressure during the extract infusion. However, bolus
      injection of all the extracts caused a significant reduction in the blood
      pressure. Thus, the extracts of Crataegus meyeri have a hypotensive and a
      potential antiarrhythmic action on ischaemic myocardium and may possess active
      principles.

PMID- 10960897
TI  - Aspects of the male reproductive toxicity/male antifertility property of
      andrographolide in albino rats: effect on the testis and the cauda epididymidal
      spermatozoa.
AB  - Previous work has shown that Andrographis paniculata leaf, when fed to male
      albino rats, causes the arrest of spermatogenesis. The present study was
      undertaken to investigate whether andrographolide, one of the major constituents
      of this plant, is responsible for such an effect. The compound was administered
      to 3-month-old male Wistar albino rats at two dose levels, for 48 days. Fertility
      tests, analysis of the counts, motility and abnormalities of the cauda
      epididymidal spermatozoa, and histopathological-evaluation of the testis were
      carried out. The results showed that sperm counts decreased, the spermatozoa were
      not motile, and several of them possessed abnormalities. The seminiferous
      epithelium was-thoroughly disrupted and in the seminiferous tubules, fully
      differentiated spermatozoa were far too limited; cells in the divisional stages
      were prevalent; multinucleate giant cells were abundant and Leydig cells appeared
      intact. It is inferred that andrographolide could affect spermatogenesis by
      preventing cytokinesis of the dividing spermatogenic cell lines. The
      multinucleate giant cells are comparable to the symplasts generated by
      cytochalasin-D and ursolic acid due to action at stages V-VII of the
      spermatogenic cycle. Sertoli cell damage and spermatotoxic effects are also
      apparent. Thus, the study points to a male reproductive toxic effect of this
      compound when used as a therapeutic; the study also confirms the possible
      prospective use of andrographolide in male contraception.

PMID- 10960898
TI  - The presence of cholinomimetic and calcium channel antagonist constituents in
      Piper betle Linn.
AB  - The crude aqueous extract of Piper betle leaves (Pb.Cr) was studied for the
      possible presence of cholinomimetic and calcium channel antagonist constituents.
      Pb.Cr at doses of 1-10 mg/mL caused a moderate spasmogenic effect in isolated
      guinea-pig ileum and this activity was concentrated in the aqueous fraction,
      which was found to be about 5 times more potent. Pretreatment of the tissue with
      atropine (1 microM) but not hexamethonium (100 microM) completely abolished the
      contractile effect of the aqueous fraction indicating a cholinergic (muscarinic)
      mechanism. In isolated rabbit jejunum preparations Pb.Cr did not produce a
      significant increase in the spontaneous contractions, but instead produced a dose
      dependent (0.03-3.0 mg/mL) inhibition of spontaneous activity. Activity-directed
      fractionation revealed that the spasmolytic action was concentrated in the ethyl
      acetate fraction. When tested against K(+)-induced contractions, both Pb.Cr and
      its ethyl acetate fraction (Pb.EtAc) caused a dose-dependent inhibition,
      suggesting calcium channel blockade (CCB). The potent CCB effect of the crude
      extract and its ethyl acetate fraction was confirmed when pretreatment of the
      tissue with Pb.Cr or Pb.EtAc shifted the Ca(++) dose-response curves to the right
      in a dose-dependent manner. These data indicate that the plant contains
      cholinomimetic and possible calcium channel antagonist constituents, which are
      concentrated in the aqueous and ethyl acetate fractions respectively. It is
      suggested that some of the traditional uses of this plant may be explained on the
      basis of these activities.

PMID- 10960899
TI  - Role of curcumin in idiopathic inflammatory orbital pseudotumours.
AB  - The present report, describes for the first time the clinical efficacy of
      curcumin, the active constituent of rhizomes of Curcuma longa, in the treatment
      of patients suffering from idiopathic inflammatory orbital pseudotumours.
      Curcumin was administered orally at a dose of 375 mg/3 times/day orally for a
      period of 6-22 months in eight patients. They were followed up for a period of 2
      years at 3 monthly intervals. Five patients completed the study, out of which
      four recovered completely and in one patient the swelling regressed completely
      but some limitation of movement persisted. No side effect was noted in any
      patient and there was no recurrence. It is suggested that curcumin could be used
      as a safe and effective drug in the treatment of idiopathic inflammatory orbital
      pseudotumours.

PMID- 10960900
TI  - LCC, a cerebroside from Lycium chinense, protects primary cultured rat
      hepatocytes exposed to galactosamine.
AB  - Primary cultures of rat hepatocytes exposed to galactosamine (GalN) were used as
      a screening system to assess whether a new cerebroside, LCC, isolated from the
      fruits of Lycium chinense, exhibits hepatoprotective activity. Cultured rat
      hepatocytes injured with GalN routinely release glutamic pyruvic transaminase
      (GPT) and sorbitol dehydrogenase (SDH) into the culture medium. Treatment of
      these GalN-injured primary cultures with LCC markedly blocked the release of both
      GPT and SDH in a dose-dependent manner over concentrations of LCC ranging from 1
      microM to 10 microM. To investigate the mechanism of action for the
      hepatoprotective activity of LCC, the extent of [(3)H]-uridine incorporation into
      RNA was measured in GalN-injured cultures of rat hepatocytes. [(3)H]-Uridine
      incorporation was significantly decreased in injured hepatocytes. LCC, however
      significantly restored the incorporation of [(3)H]-uridine into RNA in a dose
      dependent manner over concentrations ranging from 1 microM to 10 microM. LCC also
      blocked the suppression of RNA synthesis caused by actinomycin D in a dose
      dependent manner. These data suggest that LCC may have prominent hepatoprotective
      activity and that its therapeutic value should be investigated further.

PMID- 10960901
TI  - Evaluation of massage with essential oils on childhood atopic eczema.
AB  - Childhood atopic eczema is an increasingly common condition in young children. As
      well as being irritating to the child, it causes sleepless nights for both the
      child and the family and leads to difficulties in parental relationships and can
      have severe effects on employment. A group of eight children, born to
      professional working mothers were studied to test the hypothesis that massage
      with essential oils (aromatherapy) used as a complementary therapy in conjunction
      with normal medical treatment, would help to alleviate the symptoms of childhood
      atopic eczema. The children were randomly allocated to the massage with essential
      oils group and both counselled and massaged with a mixture of essential oils by
      the therapist once a week and the mother every day over a period of 8 weeks. The
      preferred essential oils, chosen by the mothers for their child, from 36 commonly
      used aromatherapy oils, were: sweet marjoram, frankinsence, German chamomile,
      myrrh, thyme, benzoin, spike lavender and Litsea cubeba. A control group of
      children received the counselling and massage without essential oils. The
      treatments were evaluated by means of daily day-time irritation scores and night
      time disturbance scores, determined by the mother before and during the
      treatment, both over an 8 week period; finally general improvement scores were
      allocated 2 weeks after the treatment by the therapist, the general practitioner
      and the mother. The study employed a single case experimental design across
      subjects, such that there were both a within-subject control and between-subjects
      control, through the interventions being introduced at different times. The
      results showed a significant improvement in the eczema in the two groups of
      children following therapy, but there was no significant difference in
      improvement shown between the aromatherapy massage and massage only group. Thus
      there is evidence that tactile contact between mother and child benefits the
      symptoms of atopic eczema but there is no proof that adding essential oils is
      more beneficial than massage alone. Further studies on the essential oil massage
      group showed a deterioration in the eczematous condition after two further 8 week
      periods of therapy, following a period of rest after the initial period of
      contact. This may have been due to a decline in the novelty of the treatment, or,
      it strongly suggests possible allergic contact dermatitis provoked by the
      essential oils themselves. The results of this study indicate the necessity of
      prolonged studies with novel plant extracts as short-term beneficial results
      could be overturned by adverse effects after repeated usage.

PMID- 10960902
TI  - Protective effect of leaf extract of Ficus hispida Linn. against paracetamol
      induced hepatotoxicity in rats.
AB  - The methanol extract of the leaves of Ficus hispida Linn. (Moraceae) was
      evaluated for hepatoprotective activity in rats by inducing acute liver damage by
      paracetamol (750 mg/kg, p.o.). The extract at an oral dose of 400 mg/kg exhibited
      a significant protective effect by lowering the serum levels of transaminase
      (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). These biochemical
      observations were supplemented by histopathological examination of liver
      sections. The activity of extract was also comparable to that of Liv-52 a known
      hepatoprotective formulation.

PMID- 10960903
TI  - The pharmacological action of Rhoicissus tridentata on isolated rat uterus and
      ileum.
AB  - Decoctions and infusions of Rhoicissus tridentata subsp cuneifolia (Vitaceae)
      roots and lignotubers are widely used in South African traditional herbal
      remedies during pregnancy. The pharmacological action of an aqueous extract of R.
      tridentata subsp cuneifolia roots was investigated using isolated rat uterus and
      ileum. The extract directly stimulated concentration dependent contractions of
      the uterus and ileum. Pretreatment with the muscarinic antagonist atropine (40
      nM) and the cyclooxygenase inhibitor indomethacin (5 microM) both blocked the
      contractile response to the Rhoicissus extract suggesting that muscarinic
      receptors and cyclooxygenase metabolites could be involved in the contractile
      response to the extract. The serotonergic antagonist methysergide (1 microM) and
      the alpha-adrenoceptor antagonist prazosin (2 microM) had no effect on the direct
      action of the extract. This infers that the contractile response to the plant
      extract is independent of serotonin receptors and alpha-adrenoceptors.

PMID- 10960904
TI  - Antiinflammatory activity and chemical composition of extracts of Verbena
      officinalis.
AB  - In an attempt to locate the biologically active fraction(s) of the plant Verbena
      officinalis Linn. (Verbenaceae), a preliminary screening of successive petroleum
      ether, chloroform and methanol extracts of aerial parts for antiinflammatory
      activity using carrageenan paw oedema model was carried out. All three extracts
      were found to exhibit antiinflammatory activity with the chloroform extract being
      the most active. Chemical investigations of petroleum ether and chloroform
      extracts led to the isolation of beta-sitosterol, ursolic acid, oleanolic acid, 3
      epiursolic acid, 3-epioleanolic acid, and minor triterpenoids of derivatives of
      ursolic acid and oleanolic acids. Chromatographic purification of the methanol
      extract yielded two iridoid glucosides, verbenalin and hastatoside, a
      phenylpropanoid glycoside, verbascoside and beta-sitosterol-D-glucoside.

PMID- 10960905
TI  - Extract prepared from the bark of Cinnamomum cassia Blume prevents glutamate
      induced neuronal death in cultured cerebellar granule cells.
AB  - We studied the protective effect of a water extract from the bark of Cinnamomum
      cassia Blume on glutamate-induced neuronal death by MTT assay and its action on
      (45)Ca(2+) influx using cultured rat cerebellar granule cells. In a dose
      dependent manner, this extract (10(-5)-10(-4) g/mL) significantly protected
      against glutamate-induced cell death and also inhibited glutamate-induced
      (45)Ca(2+) influx. These results suggest that the bark of Cinnamomum cassia has a
      protective effect on glutamate-induced neuronal death through the inhibition of
      Ca(2+) influx.

PMID- 10960906
TI  - Antioxidant action of extract of the traditional medicinal plant Rhazya stricta
      Decne. in rats.
AB  - The effects of a leaf extract of the traditional medicinal plant Rhazya stricta
      (0.25, 1.0 and 4.0 g/kg/day for 3 days) on reduced glutathione (GSH), lipid
      peroxidation (LP) and ascorbic acid (AA) concentrations in the liver and kidneys
      were studied in rats 24 h after the last dose. The plant extract, at a dose of
      0.25 g/kg, did not significantly affect the concentrations of GSH, LP or AA in
      the liver or kidneys. At a dose of 1.0 g/kg, the plant extract significantly
      increased the GSH concentration in the liver, but did not affect the GSH
      concentration in the kidneys, or LP or AA in the liver or kidneys. The plant
      extract (4.0 g/kg) significantly increased the GSH and decreased LP peroxidation,
      but did not affect the AA concentrations in the liver and kidneys. It may be
      concluded that the R. stricta extract, at some of the doses used, has antioxidant
      actions in the rat.

PMID- 10960907
TI  - Inhibition of lipogenesis by pycnogenol.
AB  - The influence of pycnogenol on the adipose conversion of 3T3-L1 cells by insulin
      was studied. In week 3 of culture with insulin, pycnogenol was found to inhibit
      significantly the expression of glycerophosphate dehydrogenase (p < 0.01). This
      finding suggests that pycnogenol inhibits the accumulation of lipid droplets in
      adipose tissue.

PMID- 10960908
TI  - Patents alert

PMID- 10960909
TI  - Selected bibliography

PMID- 10960910
TI  - Error-systematics of determining simultaneously the (6 )Li /(7)Li and the
      (10)B/(11)B abundance ratios as Li(2)BO(2)(+): considerations for analyte
      elements of varying isotopic abundance patterns.
AB  - In the Li(2)BO(2)(+) ion beam method of isotopic analysis of elements, the (two)
      analyte isotopic abundance ratios (E( i)'s) are determined by solving a set of
      (two) simultaneous equations: f( i)(E( i)'s) = R( i) +/- delta( i), (i = 1, 2)
      where the R( i)'s are the measured isotopic molecular abundance ratios. We have
      shown recently that, in the process of solution of these equations, the
      experimental errors (delta( i)'s) are transformed into the actual errors of
      analysis, delta(E)'s, through some multiplication factors (MFs). For a given
      isotopic abundance distribution (IAD) of the Li(2)BO(2)(+) ions, the MFs are
      shown to depend on the combination of two molecular pairs (CTMPS) used as the
      monitor pairs for measurements, thereby indicating the requirement of careful
      selection of monitor pairs for avoiding large (propagated) errors in analysis. In
      this work, we study how the requirements for a correct analysis vary with the
      IADs of the elements to be analyzed. The results not only lay great emphasis on
      the need for proper selection, but also show that no CTMPS can be identified as
      the universal monitor pairs irrespective of molecular IAD. These observations
      are, moreover, independent of the actual isotopic abundances of the monitor ions
      and/or the achievable measurement accuracy (delta( i)). It is noted further that,
      depending on the IADs of the analyte elements and hence the specific IAD of the
      Li(2)BO(2)(+) ions, it may also happen that none of the different possible CTMPS
      really fits the criteria as the recommended monitor pairs, and then one has to
      ensure that the measurements are not only accurate but as perfect as possible
      (delta( i)'s --> 0) so as to achieve a reasonable accuracy in analysis. These
      findings are explained in terms of variations of MFs as a function of molecular
      IAD, and elaborated using experimental data. A comparative discussion on the
      determination of both (6)Li/(7)Li and (10)B/(11)B abundance ratios together, and
      that of either of them, as Li(2)BO(2)(+), is also presented with a view to
      highlighting different possible aspects of the involvement of computation steps
      in analysis. The important implication of the present investigation is that it
      sets guidelines for the general problem of accurately analyzing unknown samples,
      irrespective of their sources of origin. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10960911
TI  - Electrospray ionization, accurate mass measurements and multistage mass
      spectrometry experiments in the characterization of stereoisomeric isoquinoline
      alkaloids.
AB  - Mass spectrometry has been employed for the characterization of diastereoisomeric
      isoquinoline alkaloids. Electrospray ionization was used to generate MH(+) ions,
      and multistage collisionally activated spectra allowed differentiation among the
      different compounds via specific fragmentation patterns, whose mechanisms have
      also been elucidated by accurate mass measurements.

PMID- 10960912
TI  - Characterisation of membrane phospholipids and glycolipids from a halophilic
      archaebacterium by high-performance liquid chromatography/electrospray mass
      spectrometry.
AB  - Combined high-performance liquid chromatography and electrospray mass
      spectrometry (LC/ES-MS) has been used for direct characterisation of the polar
      membrane lipids in total lipid extracts from Halobacterium salinarium, a species
      of halophilic archaebacterium. The principle phospholipids found were the
      diphytanyl archaeol phosphatidylglycerol and diphytanyl archaeol
      phosphatidylglycerolphosphate methyl ester. The application of LC/ES-MS revealed
      the additional presence of diphytanyl archaeol phosphatidylglycerol sulphate The
      extracts also contained an archaeol glycolipid, initially detected in preliminary
      offline ES-MS studies, which was further characterised by LC/ES-MS and by product
      ion tandem mass spectrometry (MS/MS) as a sulphate ester of diglycosyl-2,3-di-O
      phytanyl-sn-glycerol. Whilst archaeol phospho- and glycolipids containing a
      (C(20)-C(20))-isopranyl glycerol ether core predominated, LC/ES-MS of the
      extracts from Halobacterium salinarium indicated the presence of an analogue
      containing one double bond in its isoprenyl ether core as a minor component of
      the phosphatidylglycerolphosphate methyl ester fraction, providing a further
      example of the previously recognised existence of isoprenologues of diphytanyl
      archaeols which occur as minor components of archaebacterial membrane lipids. The
      value of these techniques in compositional analysis of archaebacterial lipid
      extracts is discussed.

PMID- 10960914
TI  - A study of human coagulation factor XIII A-subunit by electrospray ionisation
      mass spectrometry.
AB  - A study of factor XIII A-subunit has been made by electrospray ionisation mass
      spectrometry. Factor XIII has been isolated and rigorously purified, and the
      intact A-subunit protein has been analysed to confirm its molecular weight
      accurately for the first time. Thrombin proteolysis of the A-subunit has been
      monitored and the resulting cleavage products, the activated A-subunit protein
      and the Activation Peptide, have been analysed by electrospray ionisation mass
      spectrometry to confirm the site of proteolysis. Facile and rapid separation of
      the Activation Peptide from the activated A-subunit protein has been achieved
      using simple on-line separation techniques. The molecular weight measurements
      have been repeated numerous times to provide an indication of the precision and
      variability of the analyses.

PMID- 10960913
TI  - Mapping the phosphorylation sites of proteins using on-line immobilized metal
      affinity chromatography/capillary electrophoresis/electrospray ionization
      multiple stage tandem mass spectrometry.
AB  - On-line immobilized metal affinity chromatography/capillary
      electrophoresis/electrospray ionization-mass spectrometry (IMAC/CE/ESI-MS) offers
      selective preconcentration of phosphorylated peptides with identification of the
      phosphorylated amino acid(s). The preconcentration provides low concentration
      limits of detection and capillary electrophoresis separates the peptides.
      Recently, we reported a fast, simple, and sensitive on-line IMAC/CE/ESI-MS/MS
      method for the determination of phosphopeptides at low-pmole levels. That work is
      expanded here by use of multiple stage tandem mass spectrometry (MS(n), n = 2,3)
      to isolate and fragment target ions to provide more reliable assignments of
      phosphorylated residues. The application of IMAC/CE/ESI-MS(n) is demonstrated by
      the analysis of tryptic digests of alpha- and beta-casein and in-gel tryptic
      digests of beta-casein.

PMID- 10960915
TI  - Determination of 2-substituted benzothiazoles of industrial use from water by
      liquid chromatography/electrospray ionization tandem mass spectrometry.
AB  - A method was developed for the analysis of 2-substituted benzothiazoles from
      wastewaters by reversed-phase liquid chromatography/electrospray ionization
      tandem mass spectrometry (LC/ESI-MS/MS). While benzothiazole (BT), 2-amino-
      (ABT), 2-methyl-, 2-thiocyanomethylthio- and 2-methylthiobenzothiazole were
      separated with a methanol gradient acidified with formic acid and detected in the
      positive mode, 2-mercapto- and 2-hydroxybenzothiazole (OHBT) as well as
      benzothiazole-2-sulfonic acid (BTSA) were separated with the addition of ammonium
      acetate and detected in the negative ion mode. Detection limits range from 10 ng
      L(-1) for ABT to 200 ng L(-1) for OHBT after direct injection of 100 uL sample
      volumes, while BT requires 2.5 ug L(-1). The method is, thus, suitable for direct
      analysis in wastewaters. Its application to tannery effluent samples revealed,
      that, besides a 90-95% elimination of total benzothiazoles, the concentration of
      OHBT and BTSA increased during the biological treatment. Copyright 2000 John
      Wiley & Sons, Ltd.

PMID- 10960916
TI  - High-throughput cytochrome P450 (CYP) inhibition screening via cassette probe
      dosing strategy. I. Development of direct injection/on-line guard cartridge
      extraction/tandem mass spectrometry for the simultaneous detection of CYP probe
      substrates and their metabolites.
AB  - A highly efficient direct injection/on-line guard cartridge extraction/tandem
      mass spectrometry (DI-GCE/MS/MS) method utilizing electrospray polarity switching
      was developed for the simultaneous detection of probe substrates and marker
      metabolites of seven human hepatic cytochrome P450 (CYP) isozymes: CYP1A2, 2A6,
      3A4, 2C9, 2C19, 2D6 and 2E1. Microsomal incubations were terminated with formic
      acid, centrifuged, and the resulting supernatants were injected for analysis by
      DI-GCE/MS/MS. This method employed an extremely short C(18) cartridge (4 mm in
      length) which allowed rapid cleanup of sample matrices while retaining the
      analytes an appropriate time (2. 0-2.2 min). From 1.5 to 2.7 min the effluent was
      directed to the mass spectrometer for detection otherwise diverted to waste. As a
      result of the efficient on-line extraction, matrix (e.g., salts and proteins)
      suppression was minimized. In addition, no visible source contamination was
      observed and system performance (chromatographic and mass spectrometric) did not
      significantly deteriorate after 500 consecutive injections. Electrospray polarity
      switching was strategically executed on a Micromass Quattro II mass spectrometer
      by establishing dummy ion transitions to protect the analytes from the
      interference of the overwhelming noise which was unavoidable for the first
      transition scanned following each polarity switch. This unique strategy led to
      the simultaneous detection of seven CYP probe substrates and seven corresponding
      marker metabolites (12 by positive mode and 2 by negative mode).

PMID- 10960917
TI  - Positive ion electrospray ionization tandem mass spectrometry coupled to ion
      pairing high-performance liquid chromatography with a phosphate buffer for the
      quantitative analysis of intracellular nucleotides.
AB  - A novel analytical procedure has been developed for the analysis of intracellular
      nucleotide triphosphates. Positive ion electrospray ionization tandem mass
      spectrometry (MS/MS) was interfaced to ion-pairing high-performance liquid
      chromatography (HPLC) utilizing a mobile phase containing 10 mM ammonium
      phosphate, pH 6.4, with 2 mM tetrabutylammonium hydroxide and 15% acetonitrile.
      The methodology was developed to support the analysis of the 5'-triphosphate
      anabolite of the antiviral agent (-)-FTC ((2R, 5S)-5-fluoro-1-[2-(hydroxymethyl
      1,3-oxathiolan-5-yl]cytosine) in human peripheral blood mononuclear cells
      (PBMCs). In this procedure, all nucleotides were extracted from PBMCs with
      aqueous methanol, isolated with high recovery using a novel ion-pairing solid
      phase extraction procedure, and then analyzed directly with LC/MS/MS with a 10
      min analysis time. A calibration curve was generated representing (-)-FTC 5'
      triphosphate ((-)-FTCTP) concentration over the range of 0.083 to 83
      picomol/10(6) cells (approximately 0.08 to 80 picomoles on-column). Linear
      regression analysis with 1/x(2) weighting yielded a coefficient of determination
      (r(2)) of greater than 0.999. The back-calculated concentrations of all
      calibration standards had relative errors within the range of +5 to -3%. A
      preliminary assessment of intra-assay precision and accuracy, analyte stability,
      and LC/MS system stability indicated a robust method capable of being validated
      with a limit of quantitation estimated conservatively at 0.08 picomol/10(6) cells
      (approximately 0.08 picomoles on-column; signal-to-noise (S/N) = 5). The general
      method developed here should be adaptable to all purine- and pyrimidine-based
      nucleotide applications. This report provides a detailed discussion on the key
      HPLC, MS, and sample preparation procedures that hold the potential for even
      greater nucleotide sensitivity.

PMID- 10960918
TI  - Quantification of plasma lipids and apolipoproteins by use of proton NMR
      spectroscopy, multivariate and neural network analysis.
AB  - New approaches for quantification of human blood plasma lipids and
      apolipoproteins are presented. One method is based on multivariate analysis of
      proton nuclear magnetic resonance spectra of human blood plasma. Although similar
      approaches have been developed previously, this is the first time principal
      component analysis (PCA) and partial least squares regression (PLS) have been
      applied to this particular task. Further, a large proportion of the subjects in
      this study were cancer patients undergoing treatment, which introduced a new
      dimension to the quantification of lipoprotein distributions. Calibration models
      for prediction of lipids and apolipoproteins were constructed by use of PLS, and
      blind samples were used to test the predictive ability. Comparison of the
      predicted vs observed data obtained by standard clinical chemical procedures gave
      good agreement; the correlation coefficient for total plasma triglyceride was
      0.99, for total plasma cholesterol 0.98, for LDL cholesterol 0. 97, and for HDL
      cholesterol 0.88. These results are comparable with those obtained with other
      methods. The quantitative analysis of 14 components (including total cholesterol
      and total triglyceride) of human blood plasma was also undertaken using various
      neural network (NN) analyses of selected portions of the spectra. Conventional
      fully connected backpropagation neural network topologies were capable of
      providing excellent predictions for the majority of the variables, confirming and
      reinforcing literature related to this approach. However HDL triglycerides were
      poorly predicted, while intermediate-quality results were obtained for the LDL
      cholesterol, plasma apoA1 and LDL apoB variables. In these instances, applying
      significantly different neural network algorithms involving either general
      regression or polynomial neural networks in combination with genetic adaptive
      components for parameter optimisation made improved predictions.

PMID- 10960919
TI  - Aminomethylphosphonate and 2-aminoethylphosphonate as (31)P-NMR pH markers for
      extracellular and cytosolic spaces in the isolated perfused rat liver.
AB  - Aminomethylphosphonate (NMePo) and 2-aminoethylphosphonate (NEthPo) were
      evaluated as alternative pH indicators in the isolated perfused rat liver using
      (31)P-nuclear magnetic resonance (NMR). NMePo did not distribute within cells and
      remained in the extracellular space. It exhibited pH titration with a low pK(a)
      value (5.35). This behaviour makes NMePo useful for extracellular volume or
      acidic pH determination. In contrast, NEthPo accumulated within cells without
      altering liver energetic steady state, evaluated from nucleosides triphosphates
      resonances, even for prolonged (100 min) experiments. Withdrawal of NEthPo from
      perfusate revealed a residual resonance corresponding to the internalized amount
      of this phosphonate. This fraction was almost stable vs time and allowed
      determination of spin-lattice relaxation time constant T(1) within the liver (2.2
      +/- 0.3 s; n = 6). Comparison of the titration curves for NEthPo and inorganic
      phosphate revealed that the accuracy of pH determination within physiologic or
      acidic range in both cases was comparable. Finally, when extracellular pH was
      decreased, the NEthPo resonance frequency was found to undergo the same chemical
      shift variations as observed for cytosolic P(i) signal, which was in good
      agreement with a cytosolic accumulation of this phosphonate. Therefore, NEthPo
      could be considered as an interesting cytosolic pH probe suitable for (31)P-NMR
      measurements, especially when experimental conditions prevent reliable
      observation of cytosolic Pi resonance.

PMID- 10960920
TI  - High-resolution proton nuclear magnetic resonance spectroscopy of ovarian cyst
      fluid.
AB  - Most ovarian tumors are cystic structures containing variable amounts of fluid.
      Several studies of ovarian cyst fluid focus on one specific metabolite using
      conventional assay systems. We examined the potential of (1)H-nuclear magnetic
      resonance spectroscopy in evaluation of the overall metabolic composition of cyst
      fluid from different ovarian tumors. Ovarian cyst fluid samples obtained from 40
      patients with a primary ovarian tumor (12 malignant and 28 benign) were examined.
      After deproteinization and pD standardization, we performed (1)H-NMR spectroscopy
      on a 600 MHz instrument. With (1)H-NMR spectroscopy we found detectable
      concentrations of 36 metabolites with high intersample variation. A number of
      unassigned resonances as well as unexpected metabolites were found. We introduce
      an overall inventory of the low-molecular-weight metabolites in ovarian cyst
      fluid with corresponding resonances. Significant differences in concentration (p
      < 0.01) were found for several metabolites (including an unknown metabolite)
      between malignant and benign ovarian cysts. Furthermore, higher concentrations in
      malignant- and lower in benign fluids were found compared to normal serum values,
      indicating local cyst wall metabolic processes in case of malignant
      transformation. We conclude that (1)H-nuclear magnetic resonance spectroscopy can
      give an overview of low-molecular-weight proton-containing metabolities present
      in ovarian cyst fluid samples. The metabolic composition of cyst fluid differs
      significantly between benign and malignant ovarian tumors. Furthermore,
      differences between benign subgroups possibly related to histopathological
      behaviour can be detected. The presence of N-acetyl aspartic acid and 5
      oxoproline exclusively in serous cystadenoma samples is remarkable. Future
      studies will concentrate on these findings and explore the possibilities of
      extrapolating information from the in vitro studies to in vivo practice, in which
      metabolic differences between malignant and benign subtypes can be of great
      importance in a pre-operative phase.

PMID- 10960922
TI  - Quantification of short echo time (1)H signals: a request.

PMID- 10960923
TI  - Current awareness
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- 10960921
TI  - Direct in vivo observation of 5-fluorouracil release from a prodrug in human
      tumors heterotransplanted in nude mice: a magnetic resonance study.
AB  - A glucuro-conjugated carbamate derivative of 5-fluorouracil (5-FU), originally
      designed as a prodrug for antibody-directed enzyme prodrug therapy (ADEPT)
      application, has been used for direct in vivo observation of in situ 5-FU
      generation in two human colon tumors heterotransplanted in nude mice. Because of
      the very fast elimination of glucuro-conjugated drugs, this observation required
      intratumoral injection. These tumors, when becoming necrotic, are rich enough in
      beta-glucuronidase to allow (19)F magnetic resonance spectroscopy monitoring, at
      the tumor level, of both prodrug elimination and 5-FU liberation without
      preliminary treatment by a specifically targeted enzyme conjugate. Convenient
      tumors have been selected by magnetic resonance imaging (MRI) on the basis of a
      correlative study between MRI and conventional histology. This contribution is
      the first report evidencing such a direct intra-tumoral conversion of a glucuro
      conjugated prodrug into the expected active drug. This method, which should allow
      overall estimation of the beta-glucuronidase content of tumors, might also be
      helpful for selecting tumors as specific targets for non-toxic glucuro-conjugated
      prodrugs without prior treatment with a fusion protein.

PMID- 10960924
TI  - Regulatory, financial and ethical aspects of routine clinical magnetic resonance
      spectroscopy.
AB  - After years of technological development, magnetic resonance spectroscopy (MRS)
      is now being used with increasing frequency as a routine diagnostic tool for
      medical evaluation of patients. The transition of MRS from the realm of pure
      research to that of routine clinical application has been accompanied by some
      confusion regarding regulatory, financial and ethical matters. This contribution
      summarizes these issues from the author's perspective and calls for increased
      discussion and learning within the MRS community regarding practical matters
      associated with routine clinical implementation of MRS.

PMID- 10960925
TI  - To tell or not to tell: patterns of disclosure among men with prostate cancer.
AB  - This paper draws on the results of a longitudinal, qualitative study of men with
      prostate cancer (treated with prostatectomy) and their spouses. Interviews were
      conducted separately and simultaneously with men and their spouses, at three
      points in time (pre-surgery, 8-10 weeks post-surgery and 11-13 months post
      surgery). The primary focus in the paper is on men's responses to questions about
      their decisions to share information (or not) with others about their diagnosis
      and ongoing medical situation. Most men with prostate cancer avoided disclosure
      about their illness where possible, and placed great importance on sustaining a
      normal life. Factors related to limiting disclosure included men's low perceived
      need for support, fear of stigmatization, the need to minimize the threat of
      illness to aid coping, practical necessities in the workplace, and the desire to
      avoid burdening others. This study contributes to an understanding of disclosure
      issues related to prostate cancer, and raises issues about how best to be helpful
      to men, given their tendency to minimize the impact of illness, and the need for
      support.

PMID- 10960926
TI  - Coping with metastatic melanoma: the last year of life.
AB  - BACKGROUND: Few longitudinal studies have concurrently investigated cognitive
      appraisal, coping and psychological adjustment in patients with terminal cancer.
      This study aimed to (i) consider patterns of change in these variables during the
      last year of life and (ii) consider covariates associated with patients'
      psychological adjustment. METHODS AND PATIENTS: Questionnaires were sent to a
      cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between
      1991 and 1996, approximately every 3 months, for up to 2 years. A sub-sample of
      110 patients completed at least one questionnaire in the last year of life.
      Repeated measures linear regression was used to model cognitive appraisal, coping
      and psychological adjustment. RESULTS: In the last year of life, patients'
      cognitive appraisal of their disease remained relatively stable, whereas their
      use of active coping strategies increased (p=0. 04). There was some deterioration
      in psychological adjustment, particularly in patients' ability to minimize the
      impact of cancer on daily life (p=0.03), but this effect did not remain
      significant when patients' level of tiredness was included in the model.
      Cognitive appraisal, coping style and quality of life indicators were all
      associated with psychological adjustment. CONCLUSION: These findings suggest that
      while patients work hard to actively cope with their disease, they experience
      increasing levels of tiredness, and deterioration in their mood and ability to
      function in their daily lives.

PMID- 10960927
TI  - Testing health care professionals' communication skills: the usefulness of highly
      emotional standardized role-playing sessions with simulators.
AB  - Although standardized role-playing sessions (SRPS) with simulators are
      increasingly used to assess health care professionals' (HCPs) communication
      skills (CS) and the effectiveness of training workshops (TWs), nothing has been
      done to date to define the optimal emotional content of SRPS. Three emotionally
      different SRPS contexts-weakly emotional (WE-), moderately emotional (ME-), and
      highly emotional (HE-SRPS)-were, therefore, tested in order to assess induced CS
      and sensitivity to TW-related changes. The study included 25 HCPs. Tape-recorded
      SRPS, scheduled before and after the TW, were retranscribed, and assessed
      according to the Cancer Research Campaign Workshop Evaluation Manual (CRCWEM),
      which provides a rating of form, function and structure for each utterance.
      Results show that induced CS are different in WE-, ME-, and HE-SRPS, regarding
      form (HE-SRPS induced more 'directing', 'leading' or 'multiple' questions; WE:
      20.7%; ME: 19.7%; HE: 33.7% (p<0.001)); function (HE-SRPS induced more
      'inappropriate' information; WE: 6. 5%; ME: 8.2%; HE: 15.6% (p<0.001)); and
      blocking (HE-SRPS induced more 'blocking' utterances; WE: 7.2%; ME: 13.8%; HE:
      30.2% (p<0. 0001)). Finally, CS changes induced by TWs are the highest in HE-SRPS
      (14.8% increase of 'open' questions for the HE- versus 1.0% for the WE-SRPS;
      11.6% decrease of 'inappropriate' information for the HE- versus 3.3% for the WE
      SRPS; and 17.5% decrease of 'blocking' for the HE- versus 2.6% for the WE-SRPS).
      In conclusion, SRPS, with a HE content, induce more inappropriate CS. Moreover,
      they are more sensitive to TW effects. SRPS with a HE content should, thus, be
      recommended for the assessment of TW effectiveness.

PMID- 10960928
TI  - A randomized controlled trial of a brief psychoeducational support group for
      partners of early stage breast cancer patients.
AB  - Partners of breast cancer patients are relied upon for support at a time when
      their own coping abilities are taxed by the challenge of cancer, yet few studies
      have investigated psychosocial interventions that include or target the patient's
      'significant other'. Of the 118 consecutive patients approached, 36 patients and
      their partners participated in a randomized controlled trial of a brief
      psychoeducational group program for partners only. Psychometric instruments
      (including the Profile of Mood States (POMS), the Index of Marital Satisfaction
      (IMS) and DUKE-UNC Functional Social Support Scale (FSSS)) were administered pre
      test, post-test and at 3 months follow-up. The Mental Adjustment to Cancer Scale
      (MAC) was also completed by patients. Three months after the intervention,
      partners had less mood disturbance than did controls. Patients whose partners
      received the intervention reported less mood disturbance, greater confidant
      support (CS) and greater marital satisfaction.

PMID- 10960929
TI  - Enhancing cancer clinical trial management: recommendations from a qualitative
      study of trial participants' experiences.
AB  - Using a qualitative approach, a total of 55 adult patients with advanced cancer
      were interviewed to examine their perceptions of participating in early phase
      anti-cancer drug trials. Patients' views and experiences were explored, primarily
      through the use of in-depth interviews, with additional information accessed
      through two widely-used quality of life questionnaires, at the beginning of,
      during and after trial participation. The picture of trial participation
      established from this work suggests that it is a dynamic process, that has a
      different meaning and impact according to the stage of trial involvement the
      patient is experiencing. The findings identify how patients perceived the offer
      of the trial, dealt with the trial treatment, and came to terms with trial
      conclusion. The insight and understanding that this work provides in terms of the
      impact of trial involvement over time as well as details of patients'
      information, decision-making and support needs has significant implications for
      cancer clinical trial management. The recommendations put forward in this paper
      focus on acknowledging the contribution trial participants make to cancer
      research, enhancing the process of preparing patients for trial participation,
      recognizing the need for continuing care, the incorporation of patients and
      potential patients' views into the clinical trials system, and educating the
      public about clinical trials.

PMID- 10960930
TI  - A prospective, longitudinal study of the relationship of psychological work to
      duration of survival in patients with metastatic cancer.
AB  - This study is a prospective, longitudinal investigation of the psychological
      factors associated with the duration of survival in patients with metastatic
      cancers of various kinds who were receiving group psychotherapy. A correlative
      approach rather than an experimental (trials) design was used in the study
      because our aim was to relate the psychological attributes of each individual to
      survival rather than to test the efficacy of the intervention. Twenty-two
      patients with medically incurable metastatic cancer of various kinds received
      weekly group psychotherapy for up to 1 year, the great majority remaining well
      enough to attend the group for at least 8 months. During this time, they provided
      extensive verbal data, through written homework, and from notes taken by the
      therapists at interviews and during group sessions. These data were subjected to
      detailed qualitative analysis, as a result of which a number of psychological
      themes were defined. A quantitative rating was assigned to the data for each
      theme in each individual patient through team discussions. The scores for the
      individual themes were summed to produce a 'total psychological score',
      representing the degree of each patient's involvement with psychological self
      help work. The values for each patient were then related to his or her survival
      duration. Cox regression analyses showed that this composite score, and five of
      six major themes, were significantly related to survival duration. These themes
      were: ability to act and change; willingness to initiate change; application to
      self-help work; relationships with others; and quality of experience. In
      contrast, there was no relationship between survival and four standard
      psychometric measures taken at the onset of therapy. However, results on a 5
      point scale measuring the subject's expectancy that psychological efforts would
      affect the disease showed a strong relationship to survival. To control for
      differences in severity of disease as a factor possibly influencing psychological
      work, the analyses were repeated, using the survival duration predicted for each
      patient by a panel of oncologists as a covariate. Closely similar results were
      obtained. Limitations on the interpretation of the results are discussed. Within
      these limits, it appears that there is a strong association between longer
      survival and psychological factors related to the involvement of cancer patients
      in psychological self-help activities. While causality cannot be inferred,
      reasons are given for believing that this is not a result of the disease
      influencing the patients' psychology, but rather the converse.

PMID- 10960932
TI  - Evidence, or snake Oil?

PMID- 10960933
TI  - The development of an instrument to measure satisfaction with physical therapy.
AB  - BACKGROUND AND PURPOSE: Patient satisfaction continues to receive attention as a
      measure of the outcome of physical therapy intervention. However, a great deal
      more attention has been paid to the topic outside of, rather than within,
      physical therapy. This article describes the development of an instrument that
      measures patient satisfaction among physical therapists' patients and clients.
      METHOD: A 26-item instrument designed to measure the domains of patient
      satisfaction among patients was developed by the authors in preparation for this
      study and field tested on patients from several sites comprising a large clinical
      operation. Descriptive statistics and estimates of reliability of measurements
      obtained with the instrument were computed. Reliability and validity were
      assessed. A total of 289 individuals completed the instrument. RESULTS: The
      coefficient for reliability (Cronbach alpha=.99) obtained for the instrument was
      clearly within a desired range. Different types of validity were established as
      well. CONCLUSION AND DISCUSSION: Instruments typically used by physical
      therapists to measure patient satisfaction have undergone little psychometric
      analysis. This instrument appears to meet the criteria required to make it a
      useful tool for measuring patient satisfaction.

PMID- 10960931
TI  - Challenges posed by non-random missing quality of life data in an advanced-stage
      colorectal cancer clinical trial.
AB  - Effects of variations in agent, dose, and route of treatment administration on
      patient reported quality of life (QOL) were examined for 279 patients enrolled on
      a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for
      advanced colorectal cancer. Patients completed QOL questionnaires at
      randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints
      considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and
      hand/foot sensitivity); physical functioning; and emotional functioning. Patient
      compliance with the QOL assessment schedule was good, supporting the feasibility
      of including QOL measures in cooperative group trials. However, death and
      deteriorating health produced substantial missing data. Cross-sectional analyses
      indicated that the seven therapeutic arms did not differ in their impact on QOL.
      Unfortunately, longitudinal analyses of the QOL data were inappropriate given non
      random missing data. Graphical presentation of non-random missing data identified
      the seriousness of this problem and its effect on potential conclusions about QOL
      during treatment. This problem appears to be particularly challenging in the
      context of advanced-stage disease. Failure to recognize the presence of non
      random missing data can lead to serious overestimates of patient QOL over time.

PMID- 10960934
TI  - Measurements used to characterize the foot and the medial longitudinal arch:
      reliability and validity.
AB  - BACKGROUND AND PURPOSE: Abnormality in the structure of the medial longitudinal
      arch of the foot is commonly thought to be a predisposing factor to injury. The
      purpose of this investigation was to compare the reliability and validity of
      several measurements used to characterize various aspects of the foot, including
      the medial longitudinal arch. SUBJECTS: One hundred two feet (both feet of 51
      subjects) were measured to establish a reference database. From this group, a
      subset of 20 feet (both feet of 10 subjects) was used to determine intertester
      and intratester reliability. Radiographs of a further subset of 10 feet (right
      feet of 10 subjects) were used to determine validity. METHODS: Five foot
      measurements were taken in 2 stance conditions: 10% of weight bearing and 90% of
      weight bearing. RESULTS: Intraclass correlation coefficients (ICCs) for
      intertester and intratester measurements were between.480 and.995. The most
      reliable method of characterizing arch type in 10% of weight bearing between
      testers was dividing navicular height by foot length in 10% of weight bearing.
      However, this measure yielded highly unreliable measurements in 90% of weight
      bearing. The most valid measurements were navicular height divided by truncated
      foot length, navicular height divided by foot length in 10% of weight bearing,
      and navicular height divided by foot length in 90% of weight bearing. Dorsum
      height at 50% of foot length divided by truncated foot length showed relatively
      high intertester reliability (ICC=.811 in 10% of weight bearing, ICC=.848 in 90%
      of weight bearing) and validity (ICC=.844 in 10% of weight bearing, ICC=.851 in
      90% of weight bearing). CONCLUSION AND DISCUSSION: These data suggest that, of
      the measures tested, the most reliable and valid method of clinically assessing
      arch height across 10% and 90% of weight bearing was dividing the dorsum height
      at 50% of foot length by truncated foot length.

PMID- 10960935
TI  - Improved scaling of the gross motor function measure for children with cerebral
      palsy: evidence of reliability and validity.
AB  - BACKGROUND AND PURPOSE: This study examined the reliability, validity, and
      responsiveness to change of measurements obtained with a 66-item version of the
      Gross Motor Function Measure (GMFM-66) developed using Rasch analysis. SUBJECTS
      AND METHODS: The validity of measurements obtained with the GMFM-66 was assessed
      by examining the hierarchy of items and the GMFM-66 scores for different groups
      of children from a stratified random community-based sample of 537 children with
      cerebral palsy (CP). A subset of 228 children who had been reassessed at 12
      months was used to test the hypothesis that children who are young (<5 years of
      age) and have "mild" CP will demonstrate greater change in GMFM-66 scores than
      children who are older ((5 years of age) and whose CP is more severe. Data from
      an additional 19 children with CP who were assessed twice, one week apart, were
      used to examine test-retest reliability. RESULTS: The overall changes in GMFM-66
      scores over 12 months and a time ( severity ( age interaction supported our
      hypotheses. Test-retest reliability was high (intraclass correlation
      coefficient=.99). CONCLUSION AND DISCUSSION: This study demonstrated that the
      GMFM-66 has good psychometric properties. By providing a hierarchical structure
      and interval scaling, the GMFM-66 can provide a better understanding of motor
      development for children with CP than the 88 item GMFM and can improve the
      scoring and interpretation of data obtained with the GMFM.

PMID- 10960936
TI  - Use of visual feedback in retraining balance following acute stroke.
AB  - BACKGROUND AND PURPOSE: Visual feedback related to weight distribution and center
      of-pressure positioning has been shown to be effective in increasing stance
      symmetry following stroke, although it is not clear whether functional balance
      ability also improves. This study compared the relative effectiveness of visual
      feedback training of center-of-gravity (CoG) positioning with conventional
      physical therapy following acute stroke. SUBJECTS: Forty-six people who had
      strokes within 80 days before the study, resulting in unilateral hemiparesis, and
      who were in need of balance retraining participated. METHODS AND MATERIALS:
      Initially, subjects were randomly assigned to visual feedback or conventional
      physical therapy groups for balance retraining until 16 subjects per group were
      recruited. The next 14 subjects were assigned to a control group. All subjects
      received physical therapy and occupational therapy (regular therapy) 2 hours a
      day, and subjects in the 2 experimental groups received additional balance
      training 30 minutes a day until discharge. The visual feedback group received
      information about their CoG position as they shifted their weight during various
      activities. The conventional therapy group received verbal and tactile cues to
      encourage symmetrical stance and weight shifting. Static (postural sway) and
      activity-based measures of balance (Berg Balance Scale, gait speed, and the Timed
      "Up & Go" Test) were contrasted across the 3 groups at baseline, at discharge,
      and at 1 month following discharge using an analysis of variance for repeated
      measures. RESULTS: All groups demonstrated marked improvement over time for all
      measures of balance ability, with the greatest improvements occurring in the
      period from baseline to discharge. No between-group differences were detected in
      any of the outcome measures. CONCLUSION AND DISCUSSION: Visual feedback or
      conventional balance training in addition to regular therapy affords no added
      benefit when offered in the early stages of rehabilitation following stroke.

PMID- 10960937
TI  - Predicting the probability for falls in community-dwelling older adults using the
      Timed Up & Go Test.
AB  - BACKGROUND AND PURPOSE: This study examined the sensitivity and specificity of
      the Timed Up & Go Test (TUG) under single-task versus dual-task conditions for
      identifying elderly individuals who are prone to falling. SUBJECTS: Fifteen older
      adults with no history of falls (mean age=78 years, SD=6, range=65-85) and 15
      older adults with a history of 2 or more falls in the previous 6 months (mean
      age=86.2 years, SD=6, range=76-95) participated. METHODS: Time taken to complete
      the TUG under 3 conditions (TUG, TUG with a subtraction task [TUGcognitive], and
      TUG while carrying a full cup of water [TUGmanual]) was measured. A multivariate
      analysis of variance and discriminant function and logistic regression analyses
      were performed. RESULTS: The TUG was found to be a sensitive (sensitivity=87%)
      and specific (specificity=87%) measure for identifying elderly individuals who
      are prone to falls. For both groups of older adults, simultaneous performance of
      an additional task increased the time taken to complete the TUG, with the
      greatest effect in the older adults with a history of falls. The TUG scores with
      or without an additional task (cognitive or manual) were equivalent with respect
      to identifying fallers and nonfallers. CONCLUSION AND DISCUSSION: The results
      suggest that the TUG is a sensitive and specific measure for identifying
      community-dwelling adults who are at risk for falls. The ability to predict falls
      is not enhanced by adding a secondary task when performing the TUG.

PMID- 10960938
TI  - Managing maneuverability and rear stability of adjustable manual wheelchairs: an
      update.

PMID- 10960939
TI  - Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising
      alternative.
AB  - Gemcitabine (Gemzar) was originally approved for use in combination with
      cisplatin (Platinol) for the treatment of advanced non-small-cell lung cancer
      (NSCLC). Research began to focus on combining gemcitabine with newer drugs, such
      as carboplatin (Paraplatin), vinorelbine (Navelbine), the taxanes, and the
      camptothecins, when it became clear that these agents had potentially increased
      efficacy and fewer side effects than the standard treatment. This article will
      briefly review the original experience with the gemcitabine/cisplatin doublet and
      then examine the experience to date with non-cisplatin-based gemcitabine doublet
      combinations in the treatment of advanced NSCLC.

PMID- 10960940
TI  - Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung
      cancer.
AB  - Because the majority of patients with stage IIIA N2 non-small-cell lung cancer
      (NSCLC) ultimately die of distant metastases, recent efforts to improve their
      intermediate- and long-term survival have focused on neoadjuvant chemotherapy
      (with or without radiotherapy) as an induction regimen followed by surgical
      resection. Over the last 15 years, more than 25 phase II trials and two small
      randomized phase III trials were terminated early because interim analyses
      confirmed the feasibility of the neoadjuvant approach and suggested a twofold
      increase in overall survival time compared to surgery alone. The gemcitabine
      (Gemzar)/cisplatin (Platinol) regimen proved effective in unresectable locally
      advanced and metastatic NSCLC. Consequently, it is logical to investigate the
      activity of this combination in locally advanced NSCLC. Preliminary results of
      five phase II trials have reported an average response rate > 60% in a mixed
      study population (IIIA and IIIB). Treatment is well tolerated. In studies using
      the 4-week schedule, the gemcitabine dose was frequently omitted on day 15,
      mainly due to thrombocytopenia. In January 2000, a randomized clinical trial
      (Chemotherapy for Early Stages Trial [ChEST]) was initiated in Italy to compare
      the efficacy of surgery alone vs surgery plus preoperative gemcitabine/cisplatin
      in early-stage disease (T2-3 N0, T1-2 N1, T3 N1) with the primary end point being
      progression-free survival.

PMID- 10960941
TI  - Combination chemoradiotherapy with gemcitabine: potential applications.
AB  - Gemcitabine (Gemzar) is a novel deoxycitidine drug that has demonstrated
      promising single-agent activity in non-small-cell lung cancer and has been proven
      to be a potent radiosensitizer. Although the exact mechanism of the
      radiosensitizing effect is unknown, several studies have focused on the drug's
      effect on deoxyadenosine triphosphate (dATP) pool depletion or cell-cycle
      manipulation. A number of trials have evaluated this feature of gemcitabine by
      combining chemotherapy and radiation in various doses and schedules, and those
      studies are described in this article. Gemcitabine appears to be a promising
      agent to be combined with radiation therapy. However, further clinical trials are
      needed to define optimal doses, toxicity, and efficacy.

PMID- 10960942
TI  - Gemcitabine/carboplatin combination regimens: importance of dose schedule.
AB  - Platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), in
      combination with a number of new chemotherapeutic agents, have demonstrated
      improved response or survival compared to cisplatin alone or older platinum-based
      regimens. Gemcitabine (Gemzar)-platinum combinations are of particular interest
      because of their interactive mechanisms of action, demonstrated preclinical
      synergism, and the single-agent activity of gemcitabine. Indeed, gemcitabine and
      cisplatin regimens have proven to be among the most efficacious in the palliative
      treatment of advanced non-small-cell lung cancer. In view of the reduced
      nonhematologic toxicities associated with the platinum analogue, carboplatin,
      several combinations of new agents and carboplatin have been developed and
      incorporated into clinical practice. This article describes recent clinical
      trials evaluating gemcitabine plus carboplatin, and the impact of the dosing
      schedule on the feasibility and tolerability of this combination.

PMID- 10960943
TI  - Gemcitabine, paclitaxel, and carboplatin for advanced non-small-cell lung cancer.
AB  - The purpose of this study was to evaluate the combination of gemcitabine
      (Gemzar), paclitaxel (Taxol), and carboplatin (Paraplatin) in patients with
      advanced non-small-cell lung cancer (NSCLC). Previously untreated patients with
      stage IIIB or IV NSCLC were included in this trial. A total of 69 patients from
      the phase II portion and 8 patients from the phase I portion were treated with
      gemcitabine 1,000 mg/m2 intravenously (i.v.) on days 1 and 8; paclitaxel 200
      mg/m2 as a 1-hour infusion on day 1; and carboplatin at an area under the curve
      (AUC) dose of 5.0 i.v. on day 1. Treatment courses were repeated every 21 days.
      The phase II component of the study was completed at 13 community-based practices
      within the Minnie Pearl Cancer Research Network. Of the 71 fully evaluable
      patients, 34 had an objective response, for an overall response rate of 48%; 2
      patients showed complete responses and 32 patients had partial responses. A total
      of 25 (35%) patients were stable and 12 (17%) patients progressed. The median
      response duration was 6 months (range 3 to 14 months), and the median survival
      was 9.9 months, with a 1-year survival of 47% and a 2-year survival of 21%. These
      results show that the combination of gemcitabine, paclitaxel, and carboplatin is
      safe and effective; however, randomized phase III studies are needed to prove
      this regimen is superior to other regimens.

PMID- 10960944
TI  - Interim analysis of a phase III trial. Triple- vs double-agent chemotherapy for
      advanced non-small-cell lung cancer. Southern Italy Cooperative Oncology Group.
AB  - In our previous phase I/II studies, both the cisplatin (Platinol), gemcitabine
      (Gemzar), and vinorelbine (Navelbine) (PGV), and cisplatin, gemcitabine, and
      paclitaxel (Taxol) (PGT) regimens produced a median survival of approximately 1
      year in patients with advanced non-small-cell lung cancer (NSCLC). The present
      phase III study compared the median survival of patients treated with these
      triple-drug regimens to that of patients receiving cisplatin plus vinorelbine
      (PV) or cisplatin plus gemcitabine (PG). Accrual for the trial began in 1997 and
      by December 1998, a total of 240 patients (stage IIIB, 98; stage IV, 142) had
      been enrolled. An interim survival analysis was performed in April 1999. Overall,
      151 patients had died. The median survival rates of patients in the PGV, PG, and
      PV arms were 51, 42, and 35 weeks, respectively. At the time of this analysis,
      the median survival of patients in the PGT arm could not be assessed; however,
      the 1-year projected survival rate was 58%. At multivariate Cox analysis, the
      estimated risk of death for patients receiving PGV compared with those receiving
      PV was 0.35 (95% CI, 0.16-0.77, P = .0058). Overall response rates were 47% in
      the PGV arm, 30% in the PG arm, 25% in the PV arm, and 58% in the PGT arm. Severe
      neutropenia and vomiting were significantly more frequent in patients who
      received PV than in those who received PGV. The PV regimen produced a
      significantly shorter survival compared with the PGV combination. Since this
      difference in survival complied with one of the early stopping rules, accrual in
      the PV arm was discontinued. Enrollment in the PGV, PG, and PGT arms is ongoing.

PMID- 10960945
TI  - Interim results of a phase III trial. Paclitaxel/carboplatin vs
      paclitaxel/gemcitabine in advanced non-small-cell lung cancer.
AB  - The Hellenic Cooperative Oncology Group conducted a randomized phase III trial to
      compare paclitaxel (Taxol) 200 mg/m2 i.v. 3-hour infusion on day 1 plus
      carboplatin (Paraplatin) at an area under the curve (AUC) of 6 (group A) with
      paclitaxel at the same dose plus gemcitabine (Gemzar) 1,000 mg/m2 on days 1 and 8
      (group B) every 3 weeks for a maximum of six cycles in patients with advanced non
      small-cell lung cancer. To date, 127 eligible patients have been randomized, 63
      to group A and 64 to group B, and median follow-up is 4.6 months. Preliminary
      results suggest that both combinations are well tolerated and can be administered
      at full doses. Grade 3-4 neutropenia was generally mild but more prominent in
      group A (10%) and thrombocytopenia was insignificant in both groups. Severe
      neurotoxicity, hepatotoxicity, or cardiac toxicity have not been recorded in the
      majority of patients in either group. There was a trend toward higher response
      rates in favor of group B (group B vs group A, 37.5% vs 21.8%, respectively),
      although time-to-disease progression did not differ significantly (group B vs
      group A, 7.25 vs 7.1 months, respectively). Further maturation of the study is
      needed before definitive conclusions can be drawn.

PMID- 10960946
TI  - Gemcitabine/Alimta in locally advanced or metastatic non-small-cell lung cancer.
AB  - The search for new combination chemotherapeutic regimens for the treatment of non
      small-cell lung cancer is motivated not only by the desire to increase the
      objective tumor response and survival rates, but also by the desire to reduce
      toxicity, decrease symptoms, and improve the psychological well-being of treated
      patients. At present, the overall phase II response rates with existing
      combination chemotherapeutic regimens are approximately 15% to 30%, and the
      median survival rates are about 8 to 9 months. The median 1-year survival rates
      are about 30% to 40%, while the 2-year survival rates are only about 10% to 15%.
      Thus, while we have made substantial progress in the treatment of this disease,
      the long-term outcome is still relatively bleak. This article reviews the results
      of a phase I trial with a new combination chemotherapeutic regimen (gemcitabine
      [Gemzar] and the novel antifolate, Alimta), and outlines the rationale for, and
      design of, an ongoing phase II trial.

PMID- 10960947
TI  - Office education: "lunch says this is an atrial septal defect".

PMID- 10960948
TI  - The New World of pediatric cardiology: issues and answers.

PMID- 10960949
TI  - The genetic basis of congenital heart disease.

PMID- 10960950
TI  - Effective use of the consultant, laboratory testing, and echocardiography for the
      pediatric patient with heart murmur.

PMID- 10960951
TI  - Congenital cardiac surgical strategies and outcomes: HEARTS.

PMID- 10960952
TI  - Screening and management of hyperlipidemia in children.

PMID- 10960953
TI  - Pediatric sudden cardiac death: what the pediatrician needs to know.

PMID- 10960954
TI  - From then to now: a resident's perspective of pediatric cardiology.

PMID- 10960955
TI  - [Editorial "Alpine medicine updated"].

PMID- 10960956
TI  - [Respiratory adaptation to altitude and risk factors due to respiratory
      illnesses].
AB  - Adaptation to altitude is a complex ability of the organism which involves
      primarily the cardiovascular and respiratory system in order to increase the
      oxygen supply for body tissues. Cardiovascular adaptations to rapid altitude
      challenge are regulated sympathetically and manifest themselves first of all as
      variations of cardiac output, systolic blood pressure and heart rate at rest.
      However, respiration plays an important role in compensating hypobaric hypoxia at
      altitude. The hypoxic ventilatory response (HVR) to alveolar hypoxia expressed as
      alveolar hyperventilation happens within a very short period of exposure to
      hypoxic conditions. This immediate adaptation response is followed by the
      acclimatization period, which encompasses longer lasting compensation processes
      such as the increase of blood hemoglobin concentration improving the arterial
      oxygen content. This final stage of adaptation is reached within days or weeks of
      persisting exposure and will vary somewhat depending on the degree of altitude.
      For healthy, acclimatized individuals the oxygen supply to the organism does not
      limit the exercise performance at moderate altitudes and higher. However, above
      5000 meters (15,000 ft) long term adaptation cannot occur because oxygen
      diffusion becomes a limiting factor to physical exercise capacity. Altitude
      related disorders are contributing significantly to the morbidity and mortality
      of non-acclimatized individuals. Subjects already suffering from symptomatic
      underlying respiratory disease and hypoxemia at rest have a higher risk and
      incidence of altitude adaptation disorders even at lower altitudes. Therefore,
      several diseases with impaired respiratory function are contraindicated for any
      stay at altitude.

PMID- 10960958
TI  - [Function and repertoire of the immune system in body's defense].
AB  - This is a minireview on the organisation and activity of the human immune system
      with special reference to sport and--more precisely--stress by mountaineering.
      The activation of the immune system under physical exercise is shown and the
      immune depression after the sport documented. Hence the conclusion of increased
      susceptibility to diseases in the post activation phase--a sort of depression
      after alpine sport.

PMID- 10960957
TI  - [Diagnosis and therapy of acute altitude sickness].
AB  - Today we distinguish cerebral (acute mountain sickness AMS, high altitude
      cerebral edema HACE) and pulmonal (high altitude pulmonary edema HAPE) altitude
      disorders. Incidence, predisposition and risk factors of all kinds of altitude
      sickness vary both individually and geographically. For practical reasons the
      leading symptoms are essential: altitude headache, ataxia and sudden loss of
      strength. Depending on the severity of symptoms the main emergency measures are:
      rest, descent or evacuation, warmth. Additional therapeutical measures can be
      helpful if a sudden evacuation to lower altitudes is delayed: oxygen, portable
      hyperbaric chamber, ibuprofen/naproxen, nifedipine, dexamethasone. Acetazolamide
      should not be used as an emergency therapy any more.

PMID- 10960959
TI  - [Altitude hypoxia: effects on selected endocrinological parameters].
AB  - During the past few years, the investigation of altitude hypoxia and its effect
      on metabolic functions in humans has increasingly attracted the attention of
      endocrinologists. Most of the studies have been performed as field studies at
      moderate or high altitude, but with conflicting results. One of the possible
      reasons certainly is the fact that standardisation of field studies is almost
      impossible. Furthermore, many factors such as wind, temperature, radiation and
      others, may affect certain endocrine parameters, but they cannot be individually
      quantified. Hence, their inclusion into statistical analyses of the obtained data
      is not useful. Nevertheless, several endocrine parameters were shown to be
      affected by altitude hypoxia. Among them, there is erythropoietin, a hormone
      which is well known to stimulate erythropoiesis. This hormone shows a rapid
      increase after ascent to moderate or high altitude. There is also evidence that
      urinary and serum noradrenalin levels increase significantly, whereas adrenalin
      seems to be less affected. Another "stress-hormone", cortisol, also shows a
      significant increase. Furthermore, the biologically active fraction of the
      thyroidal hormones thyroxine and triiodothyronine increases significantly. And
      last but not least, one of the most important proinflammatory cytokines,
      interleukin-6, shows a manyfold increase compared to the basal level. However,
      the clinical significance of most of these studies is not yet clear. Hence, from
      an endocrinological point of view, no specific recommendations may be given to
      people staying at moderate or high altitude.

PMID- 10960960
TI  - [Performance enhancement through training at medium altitude-- from the
      perspective of sports medicine].
AB  - In the last 20 years, maximal oxygen uptake (VO2max) of athletes in different
      sport disciplines has increased, and the world records in endurance sports have
      improved markedly. One of the factors that has influenced the increase in
      endurance performance has been perceived to be altitude training. In this paper
      we describe the advantages and disadvantages of a "regular" altitude training
      (live high/train high) aiming to improve sea level performance and compare it
      with a new method, the so called "live high/train low" method. This method uses
      the advantages and avoids the side effects of altitude exposure. Several papers
      have shown that altitude training is able to improve VO2max but the individual
      response may be substantially different. In most cases it is not possible to
      prove statistical significance and therefore we have no data about differences
      between both altitude training methods. However, it is suspected that the risk of
      overtraining is reduced in the high/low method. Although not statistically
      significant it is suggested that the "high/low" method can more efficiently
      improve endurance performance at sea level. A monitoring of submaximal variables
      of exercise performance is recommended to avoid overtraining and to control the
      development of performance. From the current knowledge the "live high/train low"
      method is suggested to be the more effective altitude training method for
      athletes.

PMID- 10960961
TI  - [Musculoskeletal problems in rock climbing--a review].
AB  - The popularity of rock climbing and the increasing number of high-level
      performing athletes have raised during the last years the incidence of
      musculoskeletal problems involving most frequently the upper extremities. This
      paper gives a survey on literature, diagnosis and treatment.

PMID- 10960962
TI  - [Optimized nutrition for alpine athletes].
AB  - Nutritional habits of athletes usually don't differ from those of the remaining
      population. Psychic as well as physical capability are nutritionally dependent.
      In order to achieve uttermost capability for athletic activities, an optimisation
      of the daily nutrition, and of the "nutrition at the mountain" is necessary. The
      alpine athlete must adapt his diet to the intensity of his physical burden on the
      one hand and to the changed conditions in the height on the other hand.
      Nutritional recommendations are discussed.

PMID- 10960963
TI  - [Physical exercise impairs the acute stage of adaptation to moderate altitude].
AB  - A recent study has reported the impairment of high altitude adaptation capacity
      by physical exercise in a decompression chamber. The aim of our protocol was to
      evaluate if physical exercise at moderate altitude in the Alps would show a
      similar effect. 8 alpinists were examined in a randomised cross-over trial at 171
      m and at 3000 m altitude under sedentary and under exercise condition (50%
      maximal workload on the bicycle ergometer four times 30 minutes during the first
      6 hours of an 8 hour observation period at each altitude). At the beginning and
      at the end of each observation period AMS scores and arterial oxygen saturation
      SaO2 were measured. The differences of the AMS scores and the differences of SaO2
      at both test conditions were compared at both altitudes. RESULTS: In comparison
      to sedentary condition, the differences between initial and final AMS scores at
      3000 m altitude were significantly higher (-0.38 +/- 0.52 vs. -1.25 +/- 0.46,
      diff 0.88, 95% CI 0.58 to 1.17, p < 0.01), as well as the difference between
      initial and final SaO2 (-0.25 +/- 0.71% vs. 2.25 +/- 1.04%, diff. -2.5%, 95% CI
      for the diff. -3.59 to -1.41, p < 0.01). AMS score and SaO2 did not change after
      exercise at 171 m altitude. CONCLUSION: Physical exercise impairs the acute stage
      of adaptation to moderate altitude. This is mainly due to the exercise-induced
      exaggeration of arterial hypoxaemia.

PMID- 10960964
TI  - [Surgery of malignant hepatobiliary tumors].

PMID- 10960965
TI  - [Anatomy of the liver].
AB  - Over the past decades, great progress has been made in surgery on the liver.
      Technical achievements and the strict application of anatomical knowledge to
      surgical practice have added a new dimension to the field of liver surgery. In
      some cases, new facts about the anatomy of the liver needed considerable time
      before being implemented. Surgery of liver metastases, primary tumours of the
      liver and not least liver transplantation have focussed the interest of visceral
      surgeons more and more on this organ. Segment-orientated liver anatomy, a
      knowledge and consideration of vascular structures, and the observance of
      anatomical landmarks are the prerequisites for successful surgery on the liver.

PMID- 10960966
TI  - [Pathology of liver tumors].
AB  - Neoplasms of the liver may arise from any cell type within the liver parenchyma.
      Hepatocellular carcinoma is by far the most common primary malignant tumour of
      the liver in adults. Indeed, it is one of the most common tumours in the world
      with striking geographic differences. These incidence rates can be explained by
      differences in Hepatitis-Virus carrier rates which they closely reflect. Nearly
      10% of malignant liver tumors are represented by cholangiocarcinoma which
      originates from small intrahepatic bile ducts. Hepatoblastoma accounts for
      approximately 5% of malignancies in childhood. Most hepatoblastomas fall into
      epithelial or mixed epithelial and mesenchymal categories. Fetal-type cells and
      embryonal-type cells represent the epithelial components. Rare primary malignant
      non-epithelial tumours are angiosarcomas, leiomyosarcomas or fibrosarcomas,
      arising from vascular or mesenchymal components of the liver respectively. All
      types of Hodgkin and Non-Hodgkin Lymphomas may secondarily involve the liver.
      Most primary hepatic lymphomas are of diffuse large B-cell type and are extremely
      rare.

PMID- 10960967
TI  - [Molecular aspects of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
      worldwide. The major risk factors for HCC development are now well defined and
      some of the multiple steps involved in hepatocarcinogenesis have been elucidated
      in recent years. However, no clear picture of how and in what sequence these
      factors interact at the molecular level has emerged yet. Malignant transformation
      of hepatocytes may occur as a consequence of various etiologies, such as chronic
      viral hepatitis, alcohol, and metabolic disorders, in the context of increased
      cellular turnover induced by chronic liver injury, regeneration and cirrhosis.
      Activation of cellular oncogenes, inactivation of tumor suppressor genes,
      overexpression of certain growth factors, and possibly telomerase activation and
      DNA mismatch repair defects may contribute to the development of HCC. Finally,
      aflatoxins have been shown to induce specific mutations of the p53 tumor
      suppressor gene, thus pointing to the contribution of environmental factors to
      tumor development at the molecular level.

PMID- 10960968
TI  - [Prognostic significance of proliferation markers in hepatocellular carcinoma
      (HCC)].
AB  - BACKGROUND: The prognosis of patients with curatively resectable hepatocellular
      carcinoma depends mainly on anatomic extent of the tumour and on the general
      condition of the patient. Given the growing evidence that proliferation indices
      may be of prognostic significance in hepatocellular carcinomas, identification
      and quantitation of proliferative capacity may be of prognostic importance.
      METHODS: We have compared four different methods to assess proliferation in a
      series of 193 curatively (R0-) resected hepatocellular carcinomas: Mitotic count,
      immunohistochemical assessment of the MIB-1- (Ki-67-), Antigen Proliferating Cell
      Nuclear Antigen (PCNA) and silverstained nucleolar organiser regions (AgNOR). The
      results obtained were compared with pathohistological stage (according to UICC),
      Edmondson Grade and with survival rate. RESULTS: In each carcinoma, we could
      demonstrate mitotic figures, MIB-1, PCNA and AgNOR dots in variable proportions.
      Significant statistical correlations were seen between Mitotic Index, the rate of
      nuclear positivity for MIB-1 and PCNA and the number of AgNOR dots. In univariate
      survival analysis tumour stage and Edmondson Grade, Mitotic Index, MIB-1 and PCNA
      Index and mean AgNOR-number were significant patients' survival influencing
      factors. Performing multivariate Cox survival analysis, Mitotic Index,
      concomitant cirrhosis, Edmondson Grade and patient age were the only significant
      independent prognostic factors. CONCLUSION: These results indicated that Mitotic
      Index is an additional prognostic parameter which could provide auxiliary
      information for patients' outcome.

PMID- 10960969
TI  - [Isolated tumor cells in primary malignant liver tumors].
AB  - The failure to reduce the mortality of patients with malignant liver tumors
      (hepatocellular carcinoma, cholangiocarcinoma) is probably a result of the early
      dissemination of cancer cells to secondary sites, which is usually missed by
      conventional diagnostic procedures used for tumor staging. Recent developments in
      the field of molecular biology enable us to detect tumor cells at a
      submicroscopic level. Therefore, over the past 10 years, sensitive assays have
      been developed to detect individual carcinoma cells disseminated to regional
      lymph nodes or distant organs. In contrast to colorectal and also breast cancer
      where disseminated tumor cells may be of additional prognostic value, few data
      exist for hepatocellular carcinomas. Until now, no relevant studies have been
      reported for cholangiocarcinoma. Alpha-fetoprotein and also albumin mRNA have
      been used for the detection of circulating micrometastatic tumor foci of
      hepatocellular carcinoma (HCC); however, the interpretation of the results has
      been equivocal. If hepatocyte-specific mRNAs are detected in the circulation, it
      is possible to infer the presence of circulating, presumably malignant, liver
      cells. The literature about the incidence of "micrometastases" and specificity of
      different assays for hepatocellular carcinomas varies tremendously. This clearly
      indicates the need for uniformity in protocols. For hepatocellular carcinoma,
      mRNA for alpha-fetoprotein and albumin is not a specific marker of circulating
      micrometastases, but may serve for treatment monitoring. Nevertheless, PCR-based
      techniques are a powerful tool in the therapeutical monitoring of hepatocellular
      carcinoma and will find their way into the daily practice of diagnostic
      histopathologists in the near future.

PMID- 10960971
TI  - [Value of CT and MRI in malignant hepatobiliary tumors].
AB  - Computed tomography (spiral-CT, multislice-CT, CT-angiography) and magnetic
      resonance imaging have been refined technologically within the last several
      years. The value of MRI in the diagnostic workup of malignant liver tumors has
      significantly increased. The reasons are the improvement of image quality, the
      reduction of acquisition time with the possibility of imaging during one breath
      hold period, the introduction of liverspecific contrast materials
      (superparamagnetic iron oxide particles, hepatocellular contrast media), contrast
      enhanced MR-angiography and magnetic resonance cholangiopancreaticography. MR
      imaging should be used--following ultrasound--more and more as primary imaging
      modality.

PMID- 10960970
TI  - [Indications for liver biopsy in liver tumors].
AB  - Significant progress has been made in the assessment of liver dysfunction by
      application of non-invasive physical and biochemical test procedures. However,
      liver biopsy remains an important tool for diagnosis, evaluation and prognosis of
      chronic liver diseases and hepatic neoplasms. Liver biopsy results are most
      useful when the biopsy is performed for well-defined indications following a
      complete work-up of the patient. In case of lesions highly suspicious for
      hepatocellular carcinoma, a biopsy should be performed in case surgical
      (curative) treatment is no option. Thus for the planning of a surgical
      intervention, biopsy of the tumor is not necessary. In case of concomitant liver
      cirrhosis, a biopsy taken from the non-neoplastic (cirrhotic) liver may help to
      assess the functional capacity or to clarify the etiology. Metastases of the
      liver with unknown primary tumor should be biopsied to obtain information of the
      primary tumor and the potential for cytostatic therapy. In case of hemangioma or
      focal nodular hyperplasia, diagnosed and confirmed by radiology or ultrasound,
      biopsy is usually not necessary. Concern has been expressed about seeding of the
      needle tract with malignant cells. Indeed, such instances have been recorded with
      various carcinomas, but they remain rare events and are seldom of clinical
      importance. With the use of needles with diameter < 1.3 mm to minimise also the
      risk of bleeding, the procedure is simple, safe and painless.

PMID- 10960972
TI  - [Malignant hepatobiliary tumors. Surgical requirements concerning preoperative
      diagnosis].
AB  - Depending on the results of the diagnostic work-up of a hepatobiliary tumour, the
      further therapeutic strategy may vary appreciably. The data needed to decide
      whether a malignant growth is resectable or not include information on the
      nature, size and location of the tumour, the number of lesions presenting,
      extrahepatic tumour-related manifestations, the individual hepatic anatomy and
      additional liver diseases. Despite the recent technical advances, the various
      diagnostic imaging procedures all have their limitations; used in combination,
      however, they can provide adequate information in 90-100% of the cases. The most
      important of these procedures are ultrasonography and spiral CT--including the
      use of contrast agents--and in some cases also MRT. Thanks to the topographic
      information they provide, the three-dimensional methods are gaining popularity.
      While angiography, scintigraphy and ERCP are useful supplementary methods, they
      do not suffice for the primary diagnosis. In some cases, intra-operative
      diagnosis may make necessary a change in the planned therapeutic procedure. The
      limitations and possibilities of the diagnostic strategy--which in no small part
      is also codetermined by the patient's prehistory and the experience of the
      examiner--are discussed.

PMID- 10960973
TI  - [Hepatocellular carcinoma: resection versus transplantation].
AB  - For decision of adequate surgical therapy and comparison of results
      differentiation of hepatocellular carcinomas (HCC) in cirrhotic and noncirrhotic
      livers is important. Liver resection is the treatment of choice for HCC in
      noncirrhotic liver. Between 4/94 and 8/99 we treated 54 patients with
      hepatocellular carcinoma (HCC) by subtotal hepatic resection (n = 40) and
      orthotopic liver transplantation (n = 14). Overall 1- and 3-year survival rates
      of the resection group were 45 and 25% (median follow up: 3.5 years). One-year
      survival in the transplantation group was 72% (median follow up: 2.2 years). In
      patients with HCC in cirrhosis in UICC stage I to III the optimal therapy is a
      controversial issue. In these patients the results after liver resection are poor
      due to high operative mortality and recurrence (3-year recurrence-free survival:
      30%). Regarding the literature, liver transplantation is the treatment of choice
      in small (< 3-5 cm, < or = 2 tumors) HCCs arising in cirrhosis with better
      outcome compared to resection. The data in the literature report 3-year-survival
      rates after liver transplantation of 60-80%. However, consequent patient
      selection is necessary for this treatment modality. Due to the limited donor
      resources liver transplantation is rarely justified in advanced tumors.

PMID- 10960974
TI  - [Small unilocular hepatocellular carcinoma (0 < 5 cm) in patients with liver
      cirrhosis. Early diagnosis, surgical indications, resection and prognosis].
AB  - In 151 (17.5%) of 861 patients with liver cirrhosis regularly screened by
      sonography and determination of alpha-fetoprotein a hepatocellular carcinoma
      (HCC) was detected. Diagnosis was verified by sonographically guided fine needle
      puncture and exceptionally by laparoscopy and direct puncture. In 34 patients
      (22.5%) selection criteria for operation were a tumour diameter under 5 cm, no
      central localisation in the liver and at least 5 mm distant from the main
      structures; furthermore multilocular HCC and intra- and extrahepatic metastases
      were contraindications. Additionally Child-Pugh-classification should be A + B
      and urea synthesis rate 6 g per day. 27 patients (80%) had esophagogastric
      varices seen at endoscopy and 20 (59%) had bleeding episodes from varices managed
      endoscopically or surgically. Types of surgical resections were segmentectomy
      [17], bisegmentectomy [10] and oncologically defined wedge resections [7] using
      controlled hypotension and interrupted occlusion of the hepatoduodenal ligament.
      4 patients (11.8%) died within 30 days of liver failure [3] and sepsis [1]. All
      patients could be followed up for eleven years: 18 patients died after 1.5-10
      years of liver failure, tumour recurrence or second tumour and a cause not
      associated with HCC, 12 patients are living. Kaplan-Meier survival curves show
      that survival at 5 years is 50% and at 10 years 34%. The main indicators for a
      good prognosis were clinically the HBsAG-activity, the Child-Pugh-classification
      and the application of autologous blood, pathologic-anatomically the
      classification and grading and histologically the absence of vascular invasion,
      absence of satellites and a number of mitoses under 7 in the visual field. For
      tumour recurrence dysplasia is of positive influence.--Liver resection remains
      the most widely used therapeutic option for treatment of HCC in cirrhosis. The
      early and long-term results can be improved by early diagnosis, strict selection
      of patients for operation and the use of well defined clinical, pathological and
      histological criteria.

PMID- 10960975
TI  - [Surgical treatment of cholangiocellular carcinoma and proximal bile duct
      tumors].
AB  - According to its different location, clinical features, treatment modalities and
      prognosis, intrahepatic cholangiocarcinoma should be well differentiated from
      proximal bile duct carcinoma. There is no therapeutic measure with curative
      potential apart from surgical treatment. Partial or extended hepatectomy is the
      treatment of choice in cholangiocarcinoma. Thereby, hilar resection in
      combination with hepatectomy is increasingly performed in proximal bile duct
      carcinomas. In most centers liver transplantation is not considered as a
      therapeutic option for irresectable cholangiocarcinomas.

PMID- 10960976
TI  - [International registry of liver tumors in liver transplantation. A registry
      update on hepatocellular carcinoma (HCC)].
AB  - In order to evaluate the impact of tumor characteristics on the outcome of
      survival following liver transplantation, a registry was established in 1992. The
      registry uses a mailout twice a year for initial reporting and for subsequent
      follow-up as the method of obtaining data. This report contains information from
      644 patients from 57 institutions worldwide. Of those patients, 249 were alive
      and free of tumor, 27 patients were alive with tumor, 132 patients had died free
      of tumor and 139 patients had died with tumor. Of the deaths, half (135) were
      tumor related and 130 were non-tumor related. 97 patients' outcomes were not
      currently known. Factors influencing survival of HCC is the size of the tumor,
      multifocality, bilobar distribution, vascular invasion and tumor grade. In a Cox
      multivariate analysis tumor size of more than 5 cm, positive nodes and a poorly
      differentiated tumor were independent predictors of survival. The presence of an
      incidental tumor has a better prognosis than that of a non-incidental tumor;
      however, the difference is less than 10% at 5 years. Thus, an incidental
      hepatocellular carcinoma in a liver transplant patient should be treated as
      seriously and aggressively as a patient who was transplanted for the indication
      of a hepatocellular carcinoma.

PMID- 10960977
TI  - [Multimodal therapy concepts in hepatocellular carcinoma].
AB  - HCC is the most severe complication of liver cirrhosis. For the majority of
      patients the chances of cure are still limited. The recent experience in liver
      transplantation for HCC in the authors unit and in other centers allows the
      definition of a subgroup of patients, with small tumors (up to 3.0 cm, or 5 cm if
      solitary), no more than 3 nodules, and the absence of portal vein tumor thrombus.
      In these patients, liver transplantation offers a disease-free survival that is
      better than after liver resection, and similar to the survival of liver
      transplantation for benign liver disease. Patients with contraindications to
      transplantation, patients in whom a long waiting-time before transplantation is
      anticipated, and patients in countries with limited access to transplantation can
      be treated with a palliative intent (because of de novo tumors) by liver
      resection. Depending on liver function and local expertise, percutaneous ethanol
      injection (PEI) can be equally effective for small HCC. Other forms of treatment
      currently being evaluated, such as radio-frequency, thermal destruction or cyro
      therapy, offer advantages similar to PEI without the need for multiple sessions.
      Further progress will probably come from a wider use of screening to detect a
      larger proportion of treatable lesions, and from strategies to prevent
      carcinogenesis in the cirrhotic liver, and possibly from innovative treatments
      such as gene therapy to alter the tumor biology.

PMID- 10960978
TI  - [Animal experiment study on pros and cons of laparoscopic interventions on the
      liver].
AB  - The safety of laparoscopic liver resections compared to open procedure was to be
      evaluated in an animal study. Besides it had to be examined, whether onco
      surgical principles could be kept sufficiently. Therefore 8 one-year-old pigs
      underwent laparoscopic liver resections; in 2 pigs left-lateral segmental
      resections were performed, in 5 left-sided hemi-hepatectomies and in one right
      sided hemihepatectomy. It became obvious that a control of the vessels around the
      v. cava inf., of the left branch of the portal vein and of the suprahepatic veins
      was not possible with sufficient safety. Extraction of the preparations was a
      further problem. According to these results laparoscopic hemihepatectomy cannot
      be recommended for clinical routine. Further indications for a laparoscopic
      operation like deroofing of liver cysts, wedge-resections or treatment of
      superficial liver injuries are to be accepted.

PMID- 10960979
TI  - [Indications and clinical application of thrombosis prophylaxis. I].

PMID- 10960980
TI  - Effect of plasma-sprayed hydroxyapatite coating on the osteoconductivity of
      commercially pure titanium implants.
AB  - Formation of a calcium phosphate layer was studied on the surfaces of plasma
      sprayed hydroxyapatite (PSHA) and sandblasted commercially pure (cp) titanium in
      simulated body fluid with ion concentrations similar to those of human blood
      plasma. The PSHA surface induced the formation of calcium phosphate surface
      layers, while the precipitation of calcium phosphate on sandblasted cp titanium
      was not detected. Histologic evaluation of in vivo tests demonstrated that
      implants with a PSHA coating enabled the growth of bone tissue into gaps with a
      depth of up to 1 mm without significant formation of intermediate fibrous tissue.
      In comparison to sandblasted cp titanium, implants with PSHA coating exhibited
      greater tolerance to unfavorable conditions during healing, such as gaps at the
      interface or primary instability of the implant. In the case of good primary
      stability of the implant, filling of the gap with fibrous tissue was observed for
      sandblasted cp titanium implants over the greater part of the surface of gaps
      with a depth of 0.3 mm. Direct contact of cp titanium implants with bone was
      achieved only when the press-fit implantation model was used.

PMID- 10960981
TI  - Maxillary ridge expansion with simultaneous implant placement: 5-year results of
      an ongoing clinical study.
AB  - With the technique of maxillary ridge expansion, 449 implants were placed in 150
      patients and observed over a period of up to 93 months. Thin maxillary ridges of
      adequate height and comprising 2 separate cortical plates with intervening
      cancellous bone were selected for maxillary ridge expansion and simultaneous
      implant placement. Two-stage implants were used and allowed to heal in a closed
      environment for 6 months prior to loading. Single and multiple teeth were
      replaced using this technique, and an estimated mean survival rate better than
      97% after a 5-year observation period was calculated (95% confidence interval of
      the mean survival estimation: 98% +/- 1%). Good esthetic and functional outcomes
      were observed.

PMID- 10960982
TI  - Correlation of peri-implant health and aspartate aminotransferase levels: a cross
      sectional clinical study.
AB  - At present, there are no diagnostic tools that permit early detection of peri
      implantitis. The purpose of this cross-sectional study was to evaluate the
      correlation of aspartate aminotransferase (AST) levels with traditional
      periodontal clinical parameters around dental implants, since AST has been
      associated with destruction of cardiac, hepatic, and periodontal tissues. Twenty
      healthy volunteers with 59 implants were recruited from the Harvard School of
      Dental Medicine clinics. Clinical parameters evaluated included: AST level,
      probing depth (mm), Gingival Index (0, 1, 2, or 3), and bleeding on probing (0 or
      1). Utilizing the site or implant as the unit of measure, the authors found a
      statistically significant association of increased AST activity with positive
      bleeding on probing, increased probing depth, and increased Gingival Index. No
      statistical correlations were found between clinical indices and increased AST
      levels when the results were examined on an individual patient basis. This cross
      sectional study was able to demonstrate a statistical correlation between
      diseased clinical periodontal parameters and elevated AST levels.

PMID- 10960983
TI  - Five-year results with fixed complete-arch mandibular prostheses supported by 4
      implants.
AB  - This study examined whether it is possible to restore an edentulous mandible with
      a complete-arch fixed prosthesis retained by only 4 implants without decreasing
      the survival rate. One hundred nineteen patients received complete-arch
      mandibular prostheses retained by 4 implants. Most patients were followed for 3
      years or more. All patients followed a routine protocol, including annual check
      ups and regular radiographic examinations. Twenty-one patients dropped out.
      Radiographic measurements used the threads of the implants as a basis for
      comparison. No indication was found that the number of supporting implants could
      have influenced the observed frequency of technical and surgical complications.
      Three implants were lost, 2 after 1 year and 1 after 5 years. A statistically
      significant difference in bone loss between the mesial and distal implants was
      found. The number of fractured resin teeth in mandibular prostheses was higher
      when patients had an implant-supported prosthesis in the maxilla. The present
      study revealed an implant survival rate of 98.6% after 5 years. Therefore, it was
      concluded that there may not be a need for more than 4 implants to support a
      fixed mandibular prosthesis, when implants at least 10 mm long can be used.

PMID- 10960984
TI  - Implants placed in an irradiated dog mandible: a morphometric analysis.
AB  - The objective of this research was to evaluate the influence of radiotherapy on
      the osseointegration of oral implants in a canine model. After the extraction of
      all mandibular premolars and first and second molars, 11 male beagles were
      divided into 3 groups. The control group (3 dogs) received no radiation. The
      second group (4 dogs) was irradiated 4 weeks after implantation. The third group
      (4 dogs) was irradiated 8 weeks before implantation. Eight implants were placed
      in each dog, in an alternating pattern: 4 non-submerged ITI Bonefit titanium
      plasma spray-coated and 4 submerged Steri-Oss hydroxyapatite-coated. The
      irradiated dogs received 4.3 Gy daily for 10 days. After 6 months of
      osseointegration, the dogs were sacrificed and each hemimandible was dissected to
      isolate the implants. Quantification of the extent of the direct bone-implant
      contact was carried out by scanning electron microscopy backscattered electron
      images that reproduced each implant in its entirety, using a digitizing table
      connected to a computer. The results were expressed as a percentage of direct
      bone-implant contact versus total perimeter accessible to bone. The bone contact
      percentage for the control group was 87% for Steri-Oss implants and 69% for the
      ITI Bonefit implants; for the animals irradiated after implantation, the
      percentages were 82 for Steri-Oss implants and 58 for ITI Bonefit implants; and
      for the animals irradiated before implantation, the percentages were 62 for Steri
      Oss implants and 28 for ITI Bonefit implants. A statistically significant
      difference appeared between the 2 types of implants (P < .001). A statistically
      significant difference was also seen between the 3 groups for both types of
      implants, except between the control group and the group irradiated after
      implantation (P = .14). This indicates that, overall, the timing of irradiation
      influences osseointegration. Osseointegration is possible before and after
      radiotherapy; however, the direct bone-implant contact increased when the
      implants were placed before irradiation.

PMID- 10960985
TI  - Mechanics of the implant-abutment connection: an 8-degree taper compared to a
      butt joint connection.
AB  - This paper presents aa comparison between the 8-degree Morse Taper and the butt
      joint aa connections between an implant and an abutment. Three-dimensional, non
      linear finite element models were created to compare the 2 connection principles
      under equal conditions. The loading configuration was thereby modeled according
      to a test setup actually used for the dynamic long-term testing of dental
      implants as required for regulatory purposes. The results give insight into the
      mechanics involved in each type of connection and are compared to actual findings
      with the testing machine. The comparison indicates the superior mechanics of
      conical abutment connections and helps to explain their significantly better long
      term stability in the clinical application.

PMID- 10960986
TI  - Gingival recession around implants: a 1-year longitudinal prospective study.
AB  - A longitudinal study was performed, which measured the soft tissue around
      implants following surgery, to determine if a predictable pattern of soft tissue
      changes could be identified. This study evaluated 63 implants in 11 patients.
      Baseline measurements were recorded at stage 2 surgery in 2-stage implant
      systems, and at stage 1 surgery in the 1-stage system. Subsequent measurements
      were recorded at 1 week, 1 month, 3 months, 6 months, 9 months, and 1 year after
      baseline measurements. The majority of the recession occurred within the first 3
      months, and 80% of all sites exhibited recession on the buccal. It is therefore
      recommended that one wait 3 months for the tissue to stabilize before either
      selecting a final abutment or making a final impression. As a general rule, one
      can anticipate approximately 1 mm of recession from the time of abutment
      connection surgery. A comparison of this study's results with data recorded in
      previously reported studies reveals clinically significant trends in the nature
      of soft tissue healing.

PMID- 10960987
TI  - Experimentally induced peri-implantitis: a review of different treatment methods
      described in the literature.
AB  - The aim of this article was to present the experimental peri-implantitis models
      described in the literature and to provide a review of currently used treatment
      methods. For this purpose, 29 English- and German-language studies published in
      internationally reviewed journals were examined for similarities and differences
      regarding animal models, types of implants, and methods used for inducing peri
      implantitis. In almost all studies, the implants were located in the mandible,
      which suggests that peri-implantitis of the maxilla has been researched very
      little. While in most studies, peri-implantitis was induced by means of ligature
      and plaque accumulation, only 3 studies have been published that attempted to
      induce peri-implantitis by means of mechanical overload. Of the latter, only one
      author observed peri-implant bone resorption. Eleven studies reporting on
      ligature-induced peri-implantitis presented enough data to be subjected to
      further statistical data analyses. Meta-analysis revealed that the period of
      ligature application, and thus the duration of plaque accumulation, generally had
      no influence on the resultant depth of the bone defect. However, when screw-type
      and cylindric implants were analyzed separately, a weakly significant positive
      effect of the duration of ligature application on the resultant defect depth was
      determined for cylindric implants (P = .092). This could imply that smooth screw
      type implants were less susceptible to ligature-induced peri-implant
      inflammation. Regenerative treatment methods included the membrane technique
      using non-resorbable membranes (guided bone regeneration), augmentation with
      autogenous bone, augmentation with bone substitute materials (hydroxyapatite or
      demineralized freeze-dried bone) or with recombinant human bone morphogenetic
      protein-2, and a combination of membrane and augmentation procedures. While all
      described methods resulted in acceptable bone gain, it seems to be difficult to
      achieve new osseointegration (reosseointegration) of treated implants. Of all
      tested treatment methods, the combination of guided bone regeneration and
      augmentation with demineralized freeze-dried bone resulted in the most favorable
      results regarding bone gain and reosseointegration.

PMID- 10960988
TI  - Cement failure loads of 4 provisional luting agents used for the cementation of
      implant-supported fixed partial dentures.
AB  - The major disadvantage of cement-retained implant-supported fixed partial
      dentures (FPDs) is difficulty in retrievability. The retentive strengths of the
      provisional luting agents usually employed in these cases are therefore an
      important consideration. This study evaluated the cement failure loads of 4
      provisional luting agents used for the cementation of FPDs supported by 2
      implants or 4 implants. Nogenol luting agent exhibited the lowest retentive
      values in both types of FPD. ImProv proved to be the most retentive cement of all
      tested. Temp Bond NE and Temp Bond presented significantly different values (P <
      .05) for the 2-implant FPD, but not for the 4-implant model. On the basis of the
      study results, it may be concluded that Nogenol appears to be more appropriate
      for cementation of both 2- and 4-implant-supported FPDs when removal of the
      provisionally cemented superstructure is anticipated.

PMID- 10960989
TI  - Healing of dehiscence defects at delayed-immediate implant sites primarily closed
      by a rotated palatal flap following extraction.
AB  - In 21 patients, 28 maxillary teeth were extracted because of periapical or
      periodontal infection, root fracture, or untreatable caries. A rotated palatal
      flap procedure was used to achieve primary soft tissue closure over extraction
      sites. At 5 to 7 weeks postextraction, 28 implants were placed. Buccal dehiscence
      type defects were treated with guided bone regeneration procedures using bovine
      bone mineral and resorbable collagen membranes. Mean defect area at the time of
      implant placement (23.7 mm2, SD 11.49) was significantly reduced at uncovering
      (0.7 mm2, SD 0.99). The mean percentage of defect reduction (clinical bone fill)
      was 97% (SD 4.26). Implants placed in compromised sites shortly postextraction
      according to the presented 2-stage protocol gave good short-term clinical
      results.

PMID- 10960990
TI  - The effect of a hydroxyapatite-reinforced polyethylene stress distributor in a
      dental implant on compressive stress levels in surrounding bone.
AB  - This study investigated various designs of stress breakers incorporated into the
      dental implant using 3-D finite element analysis. These designs employed
      hydroxyapatite-reinforced polyethylene (HRP), a material capable of inducing
      osseointegration. The most successful design was that of a dental implant with a
      peripheral HRP component that was in direct contact with the bone surrounding the
      neck of the implant. This design lowered the compressive stress values in bone
      around the neck of the implant. Attempts were also made to optimize this design.

PMID- 10960991
TI  - Influence of bed preparation on the incorporation of autogenous bone grafts: a
      study in dogs.
AB  - To study the influence of bed preparation on the incorporation of autogenous bone
      grafts in mandibles, 6 dogs with 3 different types of receptor bed were used:
      cortical, perforated, and decorticated. After 45 and 90 days, the animals were
      sacrificed and block sections of grafted and adjacent bone were removed. The
      specimens were prepared and stained with hematoxylin and eosin and Masson's
      trichromic. The autogenous bone grafts were integrated with the receptor bed,
      mainly in the perforated and decorticated groups. The poorest results were found
      in the cortical group.

PMID- 10960994
TI  - The attending model in nursing.

PMID- 10960992
TI  - The effect of veneering materials on stress distribution in implant-supported
      fixed prosthetic restorations.
AB  - In this study, the effect of various materials used in fabricating
      superstructures for implant-retained fixed partial dentures on stress
      distribution around implant tissues was investigated. Five different mathematical
      models consisting of 11,361 nodes and 54,598 elements were constructed to study
      porcelain, gold alloy, composite resin, reinforced composite resin, and acrylic
      resin veneering materials using the 3-dimensional finite element analysis method.
      MARC K7.2/Mentat 3.2 software was used for the analysis. Reference points were
      determined on the cortical bone, where perpendicular, oblique, and horizontal
      forces were applied. Stress values created by oblique and horizontal forces
      appeared to be higher than those created by vertical forces. Stress seemed to be
      concentrated at the cortical bone around the cervical region of the implant. Gold
      alloy and porcelain produced the highest stress values in this region. Stresses
      created by acrylic resin and reinforced composite resin were 25% and 15% less,
      respectively, than porcelain or gold alloy. Porcelain and gold alloy produced
      stress values at the lingual implant sites that reached the ultimate strength
      values of the cortical bone.

PMID- 10960993
TI  - Postoperative maxillary cyst following sinus bone graft: report of a case.
AB  - Sinus bone grafting with autogenous bone is routinely performed to allow
      placement of endosseous dental implants. Although numerous maxillary sinuses have
      been successfully grafted, some complications of this procedure have been
      reported. These include maxillary sinusitis, resorption, infection and possible
      failure of grafts, loss of implants after 1-stage surgery, and oroantral
      fistulae. Only one case of postoperative maxillary cyst developing in the graft
      has been reported in the literature. Here, the authors report a similar case that
      necessitated grafting of the cyst with autologous iliac bone.

PMID- 10960995
TI  - AIDS-dedicated nurses: what can be learned from their perceptions and
      experiences.
AB  - Throughout the history of the AIDS epidemic, the theoretical and empirical
      literature have emphasized the stressors related to the care of patients with
      AIDS and the reluctance of health professionals to provide AIDS care. Since the
      beginning, however, there have been individuals who dedicated themselves to the
      care of patients with AIDS. This descriptive, qualitative study explored the
      perceptions and experiences of nurses who have chosen to work on an AIDS
      dedicated unit in a New York City medical center, with regard to both their
      patients and their own personal and professional responses to caring for patients
      with AIDS. In addition to presenting the interview data of 12 AIDS-dedicated
      nurses, included are researcher observations, based on 4 months of participatory
      observation on an AIDS unit. These findings provide insight into the development
      of the relationship between nurses and their patients with HIV/AIDS and lessons
      in supporting and enriching those caregiving relationships.

PMID- 10960996
TI  - Prehospital delay with myocardial infarction: the interactive effect of clinical
      symptoms and race.
AB  - This study examined prehospital delays and clinical symptoms of myocardial
      infarction (MI) in blacks and whites and the relationship between longer delays
      and types of clinical symptoms. The convenience sample included 128 patients,
      admitted consecutively, with acute MI. Data on types of clinical symptoms of MI
      and treatment-seeking behavior were collected on day 2 or 3 after admission,
      using face-to-face semistructured interviews. The total mean delay time differed
      significantly between blacks and whites (16 hours vs. 8.8 hours, p < .05).
      Although the frequency of chest pain was similar in both blacks and whites (78%
      vs. 77%), more than twice as many blacks as whites presented with symptoms of
      dyspnea (56% vs. 24%, p < .01) and fatigue (32% vs. 17%, p < .05). There was an
      interactive effect of race-ethnicity and types of symptoms on delay (p < .05) was
      present. Delay times for whites with chest pain were shorter than for whites
      without chest pain. Delay times for blacks with dyspnea were significantly
      shorter than for blacks without dyspnea, although delay times did not differ
      between whites with and without dyspnea.

PMID- 10960997
TI  - Preventing pressure ulcers: an evaluation of four operating-table mattresses.
AB  - Pressure is a major factor in the development of pressure ulcers. This research
      focused on assessing the pressure-reducing effects of operating-table mattresses.
      Five mattresses were tested: a standard operating-table mattress, a foam
      mattress, a gel mattress, a visco-elastic polyether mattress, and a visco-elastic
      polyurethane mattress. Four intraoperative postures were evaluated: supine,
      lateral, fossa, and the Miles-Pauchet position. Interface pressure measurements
      were performed on 36 healthy volunteers. The foam mattress and the gel mattress
      seem to have little or no pressure-reducing effect; the polyurethane mattress and
      the polyether mattress reduce interface pressure significantly better (p < .001);
      but none of the mattresses reduce pressure sufficiently to prevent the occurrence
      of pressure ulcers.

PMID- 10960999
TI  - Conducting psychosocial research with children and adolescents: a developmental
      perspective.
AB  - In the past 10 years, childhood has become a focal point of concern. Children are
      viewed as symbolizing an investment in the future of societies around the world.
      In the past, knowledge about children's views was realized through objective
      measures or from representative accounts by adults (e.g., parents and teachers)
      who were thought to know the child best. Current research suggests that most
      adult representations and interpretations are only attempts to describe something
      that more or less represents the child's world. The literature suggests that in
      the past, children have been perceived mainly as objects rather than subjects of
      research interest. This perhaps reflects the viewpoint held by many that children
      are unable to comprehend and describe their world and life experiences because of
      developmental immaturity and/or that there are intrinsic difficulties in
      researching children. The purpose of this article is to describe how a child's
      developmental level affects the research process. Specifically discussed are
      developmental differences in responses to research including psychosocial
      research methods, assent, and consent with children.

PMID- 10960998
TI  - Coronary artery bypass graft surgery patients and their family member caregivers:
      outcomes of a family-focused staged psychoeducational intervention.
AB  - This experimental study examined the effectiveness of a psychoeducational
      intervention delivered over 12 weeks. The sample was comprised of 38 coronary
      artery bypass graft (CABG) surgery patient-family member caregiver dyads who
      completed all six data collection points. Experimental and control groups did not
      differ in emotional health, functional health status, or satisfaction.
      Differences in the number of self-reported complications/symptoms were not in the
      predicted direction. Improvement occurred in clinical, functional, and emotional
      outcomes; however, several symptoms, such as fatigue and pain, persisted. Family
      caregivers reported more depressive symptoms than patients preoperatively and at
      later stages of recovery. Implications include the need for instruction about the
      recovery trajectory and adequate preparation and support of home health nurses
      and family caregivers.

PMID- 10961000
TI  - Pain measurement: a comparison using horizontal and vertical visual analogue
      scales.
AB  - The McGill Pain Questionnaire (MPQ) is widely used in assessing a variety of pain
      problems. MPQ has been found to be sensitive enough to detect differences in pain
      relief and differences between acute and chronic pain. It requires, however, 5 to
      10 minutes to administer. Because of this time factor, the Short-Form McGill Pain
      Questionnaire (SF-MPQ) was developed. A visual analogue scale (VAS) was not
      included in the original MPQ but is part of the SF-MPQ. Studies addressing the
      best way to present a VAS suggest that a vertical line is easier for patients to
      see; however, the VAS on the SF-MPQ is a horizontal line. This study examined the
      relationship between SF-MPQ scores with both the horizontal and vertical VAS.

PMID- 10961001
TI  - WISECARE to support evidence in practice.

PMID- 10961002
TI  - The nursing shortage: from warning to watershed.

PMID- 10961003
TI  - [I owe my life to you].

PMID- 10961004
TI  - [Artificial sphincter in severe urinary incontinence: 9 years of experience].
AB  - OBJECTIVE: To present the results achieved with the artificial urinary sphincter
      in the treatment of 44 patients with severe urinary incontinence. METHODS: From
      April 1990 to December 1998, an artificial urinary sphincter was implanted in 44
      patients with severe urinary incontinence, aged 21 to 82 years (mean 56). These
      patients were categorized into the following groups: Group A comprised 24 males,
      aged 37 to 82 years (mean 66), who had undergone previous prostatic procedures.
      Four of them had undergone radical retropubic prostatectomy. The remaining 20 had
      undergone a total of 34 de-obstructive procedures (mean 1.7 procedures/patient;
      range 1-3); 28 were endoscopic procedures and 6 open prostatectomy. One of them
      had a previous ileocystoplasty due to severely low compliance. Ten were
      completely incontinent and were using a condom catheter (7), penile clamp (2) or
      permanent indwelling Foley catheter (1). The rest used a mean of 3.7 pads per
      day. Group B comprised 11 males with a complex urologic history: 9 had neurogenic
      dysfunction, 1 had bladder exstrophy and 1 had a previous cystectomy and Studer
      neobladder. Eight were using a condom catheter. The cuff was placed in the bulbar
      urethra in 8 (4-4.5 cm) and in the bladder neck in 4 (9-10 cm). Group C comprised
      9 women with type III stress incontinence after failed previous interventions
      (range 1-4, mean 2.7). All of these patients required at least 3 pads per day
      (mean 4.5). The cuff was placed in the bladder neck with diameters ranging from 5
      to 10 cm. RESULTS: The mean follow-up was 28.5 months (range 8-96). One patient
      died two years after implantation of the artificial sphincter which was never
      activated. In group A, 83% are socially continent and 17 do not require pads.
      Three of the 20 patients with the artificial sphincter have undergone a total of
      4 surgical revisions. In group B, the social continence rate was 63% with a 36%
      revision rate. Four patients required a complete change of the system. In group
      C, The continence rate with revision was 66%. One patient underwent two
      successive successful revisions and 3 required removal of the device, accounting
      for a failure rate of 33%. Definitive removal of the artificial sphincter was
      required in 3 females and 5 males. Aside from one male who refused a new implant,
      the rest were considered unsuitable for a new device. Six patients underwent at
      least one reoperation to change one or more parts of the system. Continence was
      recovered in 66% after the revision. CONCLUSIONS: The artificial urinary
      sphincter achieves a good continence rate in patients with severe incontinence,
      although careful patient follow-up is required.

PMID- 10961005
TI  - [5'CpG island methylation of the suppressor gene p16/CDKN2/MTS1 in renal
      carcinoma].
AB  - OBJECTIVE: To determine the methylation status of the tumor suppressor gene p16
      in patients with renal carcinoma by analysis of microsatellite polymorphisms.
      METHODS: 40 patients with sporadic renal cancer were studied. Tumor and normal
      tissue from each patient were tested for methylation status of the p16 gene by
      analysis of microsatellite polymorphisms. RESULTS: 20% showed methylation of p16.
      No correlation was found between this genetic alteration and tumor features.
      CONCLUSIONS: Methylation of p16 was found in 20% of the patients in this series.
      According to the analysis, 18.5% of renal cell carcinomas showed methylation, 50%
      of chromophobe cell carcinomas and 25% of carcinomas of Bellini's tubules. The
      rest of the histological types showed no methylation.

PMID- 10961006
TI  - [Dilemma in the treatment of angiomyolipoma].
AB  - OBJECTIVE: To present our experience with renal angiomyolipoma. METHODS: The
      series comprised 27 patients (26 female, 1 male) with renal angiomyolipoma.
      Twenty-three (85%) had unilateral renal involvement and of the 4 remaining
      patients (15%) with bilateral involvement, three (10%) had tuberous sclerosis.
      RESULTS: Due to the complications, three patients with bilateral and one patient
      with unilateral renal involvement required surgery. Mean patient follow-up was 38
      months. CONCLUSIONS: Surgery is warranted in patients with tumors of more than 4
      cm, symptomatic or associated with tuberous sclerosis. Regular control evaluation
      is indicated for tumors less than 4 cm.

PMID- 10961007
TI  - [Experience with kidney transplantation with children as donors].
AB  - OBJECTIVE: To analyze the results achieved with transplantation of children
      kidneys to adult recipients. METHODS: The results achieved with transplantation
      of children cadaver kidneys (< 15 years) from 1989 to 1994 over a follow-up
      period of at least 36 months were reviewed. Patients (n = 43) were stratified
      into group A (13 grafts from donors < or = 6 years), group B (30 grafts from
      donors > 6 years) and group C (control group), which comprised 73 patients who
      received grafts from donors of an ideal age during the same time period. All
      three groups were similar for variables considered to influence the results of
      transplantation, except for the higher incidence of hypotension in group B.
      RESULTS: The number of episodes of rejection was three-fold higher in group A
      than in the control group (p = 0.019). A higher incidence of surgical
      complications, principally vascular complications (arterial thrombosis, renal
      rotation), was found in group A versus the control group (p = 0.039). When the
      grafts transplanted en bloc from donors under 12 months were excluded from the
      analysis, the incidence of vascular or urological surgical complications in group
      A was not found to be higher than that of the control group. No difference was
      found for mean length of stay, renal function (creatininemia), graft or patient
      survival for the three groups. CONCLUSIONS: Grafts from donors more than 6 years
      old showed a similar behavior as those from donors of an ideal age. Furthermore,
      single kidneys from donors aged more than 12 months can be transplanted with
      excellent results. It is necessary to have a larger series to confirm and explain
      the high incidence of acute rejection in grafts from donors less than 6 years
      old.

PMID- 10961008
TI  - [Vascular assessment before kidney transplantation. Role of computerized helical
      tomography].
AB  - OBJECTIVE: To present our experience with helical CT for vascular assessment
      prior to renal transplantation. METHODS: In our hospital, all candidates to renal
      transplantation are referred to the Urology Transplant Unit for previous
      assessment. For the past 3 years, patients with multiple arterial calcifications
      (non linear) have been evaluated by helical CT with three-dimensional
      reconstruction of the calcification densities, which provides an accurate
      representation of the lesion. RESULTS/CONCLUSIONS: Pretransplant evaluation has
      been fundamental for individualized planning of the renal transplant surgery. The
      use of helical CT is extending in our field and it has also been utilized in
      graft donor assessment. In our experience, the extent and thickness of arterial
      wall calcifications are accurately depicted by helical CT. These findings could
      have an important significance when making pre and perioperative decisions in
      renal transplantation.

PMID- 10961009
TI  - [Metastasis priapism. Report of 4 new cases and review of the literature].
AB  - OBJECTIVE: Four additional cases of malignant priapism or priapism secondary to
      penile metastasis from urogenital tumors are presented and the literature is
      reviewed. METHODS: Chest and abdominal radiological evaluation, cavernosal and
      abdominal US, abdominal and pelvic CT and MRI, and cavernosal biopsy were
      performed for the localization and staging of the primary tumor. RESULTS:
      Conservative palliative management achieved a survival of only a few months in
      three of the patients with tumor dissemination to adjacent vital organs. Radical
      surgery was performed in one patient with tumor localized to the genital area.
      Currently, this patient has no clinical symptoms, although the follow-up is only
      4 months. CONCLUSIONS: Malignant priapism is rare and usually secondary to GU
      tumors. The prognosis is poor since it generally indicates the presence of
      multiorgan metastasis. However, the prognosis is better for single metastasis,
      which is an indication for radical surgery.

PMID- 10961010
TI  - [Tubular ectasia of the rete testis: ultrasonography findings in 19 patients].
AB  - OBJECTIVE: The sonographic findings and associated etiological conditions in 19
      patients with tubular ectasia of the rete testis are described. METHODS: 19
      patients with tubular ectasia of the rete testis diagnosed by ultrasound over a
      two-year period are presented. Twenty-seven testes showed ectasia. The mean age
      at the time of diagnosis was 59 years. US evaluation was performed with the 7-8
      MHz multifrequency linear probe (Acuson 128, Mountain View, CA, USA). The
      patients were evaluated in the supine position and the scrotal content was
      examined in the sagittal and transverse planes. A color and pulsed Doppler study
      were performed in all the cases. RESULTS: 8 patients showed bilateral
      involvement, 7 had left and 4 right tubular ectasia. Other frequently associated
      findings were spermatocele (8 cases), cord cyst (6 cases) and varicocele (5
      cases). Four patients had undergone scrotal surgery and one had a previous
      history of epididymitis. CONCLUSIONS: Tubular ectasia of the rete testis is an
      uncommon, benign condition that is usually associated with epididymal obstruction
      following trauma or infection in most of the cases. Diagnosis of tubular ectasia
      by US, in a correct clinical context, obviates the need to perform a biopsy and
      orchidectomy for its diagnosis in a vast majority of the cases.

PMID- 10961011
TI  - [Glandular cystitis. Endovesical steroid treatment].
AB  - OBJECTIVE: To report a case of cystitis glandularis, a proliferative disorder of
      the bladder mucosa whose incidence is estimated to be approximately 1%.
      METHODS/RESULTS: A case of diffuse cystitis glandularis in a male patient is
      presented. Intravesical steroid therapy achieved symptomatic resolution, although
      the proliferative mucosal lesions persist. CONCLUSION: There is currently no non
      ablative treatment that has been demonstrated to be effective in diffuse cystitis
      glandularis.

PMID- 10961012
TI  - [Cystic dilatation of the prostatic utricle].
AB  - OBJECTIVE: To report a case of cystic dilatation of the prostatic utricle.
      METHODS: A case of cystic dilatation of the prostatic utricle associated with
      right renal agenesis in a 26-year-old patient who consulted for recurrent
      orchiepididymitis and a history of hemospermia is presented. RESULTS: Physical
      examination showed a hypogastric tumor mimicking a vesical globus that was
      palpable on digital rectal examination. Ultrasonography and urethrocystoscopy
      were decisive in the diagnosis of this anomaly. The utricle was removed by the
      transperitoneal approach. Gross examination showed opening of both deferent ducts
      and right ureter (blind-ending) into the utricle. CONCLUSION: The pathological
      characteristics of this anomaly permitted its identification as cystic dilatation
      of the prostatic utricle, a condition that should be taken into account in the
      differential diagnosis of pelvic tumors in the male.

PMID- 10961013
TI  - [Iatrogenic bladder lithiasis in the Burch technique. An infrequent
      complication].
AB  - OBJECTIVE: To describe an uncommon case of iatrogenic bladder lithiasis in a
      female patient who underwent colposuspension according to the Burch technique.
      METHODS/RESULTS: A female patient who had undergone colposuspension for urinary
      stress incontinence presented with irritative bladder symptoms and dyspareunia
      two years later. Patient evaluation revealed stone formation on the nonresorbable
      suture. Stone removal was achieved endoscopically using local anesthesia and
      without compromising continence. CONCLUSION: Removal of the calculus that had
      formed on the suture was achieved by endoscopy without compromising continence.

PMID- 10961014
TI  - [Ureteral endometriosis].
AB  - OBJECTIVE: To report a case of ureteral endometriosis, an uncommon disease in the
      urological practice that is diagnosed late and may cause irreversible damage to
      the upper urinary tract. METHODS/RESULTS: A case of unilateral ureteral
      endometriosis is presented. After attempting hormonal therapy and endourological
      management, the patient eventually underwent aggressive surgical treatment.
      CONCLUSIONS: The diagnosis of ureteral endometriosis should be considered in
      women presenting with noncalculous renal obstruction, particularly premenopausal
      women of low parity or those who have had previous pelvic surgery. Only a high
      index of suspicion and the radiological supports may help to reduce the number of
      alarming nephrectomies associated to this condition.

PMID- 10961015
TI  - [Penile hematoma caused by deep dorsal vein rupture during intercourse].
AB  - OBJECTIVE: To describe a case of rupture of the deep dorsal vein of the penis
      during sexual intercourse. METHODS: A 21-year-old patient consulted at the
      emergency services for acute penis after vigorous sexual intercourse, with
      clinical features suggestive of rupture of the corpora cavernosa. RESULTS:
      Surgery demonstrated complete rupture of the deep dorsal vein of the penis, which
      was repaired. Examination showed no injury to the corpora cavernosa. CONCLUSIONS:
      Early surgical management is advocated in acute penis, since it will permit us to
      make the correct diagnosis and treat the underlying cause to avoid future
      sequelae. Rupture of the deep dorsal vein of the penis is another condition that
      should be considered in the differential diagnosis of acute penis. Its clinical
      features are similar to those of cavernosal rupture. Ultrasound and
      cavernosography are not diagnostic.

PMID- 10961017
TI  - [Epididymal tumor of adrenal remains].

PMID- 10961016
TI  - [Cystic nephroma. Report of 5 cases].
AB  - OBJECTIVE: To report 5 cases of cystic nephroma and review the clinical,
      diagnostic and therapeutic aspects. METHODS: From 1974 to 1988, 5 cases of cystic
      nephroma were diagnosed at our hospital. Patient evaluation included IVP and
      renal US, and occasionally ascending urography, fine needle aspiration biopsy and
      CT. The cyst was removed through a lumbar incision in 4 patients and nephrectomy
      in one patient. RESULTS: The patients were followed by yearly
      ultrasound/urography for 1 to 15 years. No evidence of local recurrence or
      metastatic disease has been found. CONCLUSIONS: Cystic nephroma is an uncommon,
      benign kidney disease whose etiology is unknown. Although new imaging techniques
      are available, surgical excision and histologic analysis of the tumor are the
      only effective methods to distinguish benign from malignant cystic lesions of the
      kidney. Because it is a benign lesion, surgery must be conservative. Complete
      excision of the cyst is advocated. We found a well-encapsulated, noninfiltrating
      lesion that permitted surgical excision without difficulty in most of our cases.
      Herniation of some cysts into the urinary tract is a characteristic radiological
      sign.

PMID- 10961018
TI  - Use of double J stent in a case of spontaneous ureteral extravasation of urine.
AB  - OBJECTIVES: Although there are numerous case reports of spontaneous rupture of
      the collecting system, especially including the calyceal fornix or the renal
      pelvis, spontaneous rupture of the ureter is a rare condition. METHODS: Herein,
      we present a case of a patient who suffered symptoms of acute abdomen due to
      rupture of the proximal ureter. Extensive assessment revealed no etiological
      factor as to the extravasation. RESULTS/CONCLUSIONS: The condition was managed
      conservatively by insertion of a double-J catheter. The double-J ureteral stent
      was removed on the first postoperative month under local anesthesia uneventfully.
      One year after the spontaneous ureteral extravasation, the patient remained
      without clinical problems. The diagnosis, pathogenesis and complications of this
      unusual condition are reviewed.

PMID- 10961019
TI  - Synthesis of purine derivatives of potential immunomodulatory activity.
AB  - Moving from the interest as immunomodulatory agent of ST789 was studied the
      synthesis of series of N9alkylated hypoxanthine and adenine. The synthesis and
      the chemical physical properties of these derivatives are here described.

PMID- 10961020
TI  - Aceclofenac-loaded poly-epsilon-caprolactone nanocapsules. Effect of coadjuvants
      on morphometrical properties and drug entrapment.
AB  - The physicochemical properties of aceclofenac nanocapsules, prepared by
      interfacial precipitation of poly-e-caprolactone at the oil/water interface, have
      been studied. A Central Composite Design was used to investigate the influence of
      polymerization adjuvants on these properties on the elaboration of aceclofenac
      loaded poly-e-caprolactone nanocapsules. In this way, the effect of polymer, oil
      and drug concentrations in organic phase on the size and encapsulation efficiency
      has been analyzed. The optimized nanocapsule formulation leads to use an initial
      concentration of drug (aceclofenac) of 0.8 mg/ml and 0.6% of oil (Miglyol 812),
      being the polymer and surfactant concentrations previously fixed.

PMID- 10961021
TI  - Preparation of mefenamic acid sustained release beads based on kappa-carrageenan.
AB  - Mefenamic acid (MA) is a nonsteroidal anti-inflammatory drug used as analgesic
      and antipyretic drug. Available conventional pharmaceutical forms are capsules
      and film-coated tablets given three times a day (t.t.d.). Natural polymers such
      as sodium alginate, pectin, chitosan and carregeenan, used as barriers to effect
      the drug release, are those of the main interest of researchers. The aim of the
      present study was to formulate sustained release MA-beads based on kappa
      carrageenan in order to reduce daily dose and to minimize gastrointestinal
      disturbances caused by the drug.

PMID- 10961022
TI  - Stability of capsules containing omeprazole in enteric coated pellets.
AB  - The aim of the present study was to comparatively evaluate the stability of
      capsules containing 20 mg of Omeprazole, in enteric coated pellets, from seven
      pharmaceutical laboratories on Argentine market. The stability test was performed
      under the conditions indicated by the ICH: 40 degrees C, 75% HR, with and without
      light, during a six month period. The remaining content of Omeprazole, total
      percentage of impurities and percentage of released active principle in vitro,
      were determined by HPLC. The organoleptic characteristics of the pellets were
      visually examined. The results obtained at six months indicate that, from the
      seven products studied, four were found to have a content of Omeprazole higher
      than 90% of the labeled amount, in both lighting conditions tested, and also
      comply with the USP23 specifications with respect to the release in vitro. We
      conclude that the progressive darkening of the pellets indicates, qualitatively,
      the level of degradation of the product and that the stability of Omeprazole
      depends on the correct formulation and the primary container.

PMID- 10961023
TI  - The influence of glycoprotein hormones selected properties of selected properties
      of glycoprotein hormones on their absorption after intranasal administration in
      foxes.
AB  - The absorption of glycoprotein hormones, i.e. folitropin and lutropin, whose
      approximate molecular weight is 30,000 D, were estimated for the intranasal
      administration. The maximal hormone concentrations were observed 30 minutes after
      their administration. The maximal concentration of folitropin was 32% higher than
      the maximal concentration of lutropin. Bioavailability level for foliotropin was
      138.58% compared to lutropin bioavailability level, which was considered the
      pattern bioavailability level (100%) in our experiments. It was established that
      the absorption of hormones from nasal mucous membrane depended not only on their
      molecular mass but also on the isoelectric point, content of carbohydrates and
      sialic acids. Hormonal substances of acid character, containing a greater content
      of carbohydrates and sialic acids (as in the case of folitropin) were absorbed
      from the nasal mucosa more rapidly.

PMID- 10961024
TI  - Evaluation of named binders in Rauwolfia vomitoria root tablets.
AB  - Some physical properties of Rauwolfia vomitoria root tablets were studied. Tablet
      characteristics studied were: weight uniformity, tensile strength, friability,
      disintegration time and content uniformity. Tablet property varied depending on
      the type and concentration of the binder. The tablets had type and concentration
      of the binder. The tablets had acceptable hardness and friability profiles.
      Although tablets containing 150 mg R. vomitoria root had lower tensile strength
      values. All the tablets passed the B.P. disintegration time test of 15 min.
      Moreover tablets containing 150 mg R. vomitoria root disintegrated under 1 min.
      at 4% w/w binder concentration.

PMID- 10961025
TI  - Characterisation of cannabis plants phenotypes from illegal cultivations in
      Crete.
AB  - In the present study samples of cannabis plants presented to us by the Drug
      Enforcement Units were characterised, based on the analysis of active substances.
      The fresh samples were dried in a dark room were they were kept until analysis.
      The samples included leaves, flowers roots and trunks. The analysis was performed
      by High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC)
      using standard solutions of cannabidiol, D-9 tetrahydrocannabinol, D-8
      tetrahydrocannabinol and cannabinol. Chemical analysis of the flowers revealed
      that 80% of the plants were classified as resinous phenotype while the remaining
      20% were found to be of the textile phenotype (low concentration of active
      cannabinoids). The concentration of D-9 tetrahydrocannabinol in the flowers and
      leaves ranged from 0.014 to 21.06 mg/g, of cannabinol from 0.0002 to 0.350 mg/g
      and of cannabidiol from 0.03 to 29.6 mg/g. Roots and trunks contained very small
      quantities of active substances and should not be used for phenotype
      identification. No delta-8 THC was detected in any sample. Leaves gave less
      resinous phenotypes than flowers. The use of either mathematical formula, A or B
      produced the same phenotype character for each separate part of the plant.

PMID- 10961026
TI  - Cancer, drug medication and noncompliance.
AB  - This issue is an attempt to expose the extent of compliance, respectively of non
      compliance among the oncological patients of the Central Oncological centre in
      Sofia. There are several factors that influence upon the degree of nonadherence.
      The authors make an attempt to elucidate them in order to increase the rate of
      compliance among this group of patients. The results of the analysis of the
      received data show that the level of the compliance is 92% among the studied
      cancerous patients. Despite the shown high level of compliance there are
      possibilities for the individualization of their treatment.

PMID- 10961027
TI  - Oxidant stress mechanisms in heart failure.
AB  - Evidences clearly indicate that HF is accompanied by excessive generation of OFRs
      and depletion of endogenous antioxidant system. The resultant oxidant stress
      depresses myocardial contractility and function by decreasing Ca++ uptake in
      sarcoplasmic reticulum and by impaired Ca(++)-ATPase in cardiac tissue. The
      various sources of OFRs production in HF include increased production of nitric
      oxide, cytokines, prostaglandins, auto-oxidation of catecholamines, activation of
      polymorph leucocytes and ischemia induced xanthine-xanthine oxidase. The
      prevention of oxidative stress by antioxidant translates into better metabolism
      and function of myocytes. It appears that antioxidant drugs may represent a novel
      adjunct to the existing therapeutic armamentarium in patients of HF irrespective
      of its etiology and severity.

PMID- 10961028
TI  - Assessment of chronic care need and use.
AB  - The needs assessment process is indeed complex in the social service context.
      Whereas most contexts can start with a presumption of "no need," the social
      service context frequently must start with an assumption of "need met-->change."
      In addition, underlying values--the individual's, the assessor's, the society's-
      all play a part in the judgment process. The assumption that the involvement of
      another in performing the task automatically implies a limitation on the part of
      the recipient is not warranted, nor is the assumption that the reliance on
      another by one in need automatically implies the need is met. For purposes of
      population needs assessments, it is possible to rely on presumptive
      categorizations as a function of simple response profiles. For individual care
      planning, however, additional information is essential.

PMID- 10961029
TI  - The therapeutic design of environments for people with dementia: a review of the
      empirical research.
AB  - Design of the physical environment is increasingly recognized as an important aid
      in caring for people with dementia. This article reviews the empirical research
      on design and dementia, including research concerning facility planning
      (relocation, respite and day care, special care units, group size), research on
      environmental attributes (noninstitutional character, sensory stimulation,
      lighting, safety), studies concerning building organization (orientation, outdoor
      space), and research on specific rooms and activity spaces (bathrooms, toilet
      rooms, dining rooms, kitchens, and resident rooms). The analysis reveals major
      themes in research and characterizes strengths and shortcomings in methodology,
      theoretical conceptualization, and applicability of findings.

PMID- 10961030
TI  - The therapeutic design of environments for people with dementia: further
      reflections and recent findings from the National Institute on Aging
      Collaborative studies of Dementia special care units.

PMID- 10961031
TI  - The effect of long-term care environments on health outcomes.
AB  - This study contrasts rates of mortality and of relocation to higher levels of
      care as well as trajectories of cognitive status, functional ability, depression,
      and subjective health of residents of an assisted living facility with those of a
      nursing home. Data were collected from medical records and face-to-face
      interviews with 158 residents at baseline and 4, 8, and 12 months later. All
      participants lived on a single long-term care campus. Logistic regression
      revealed that facility was not a significant predictor of mortality or
      relocations due to declining health. A repeated measures analysis of variance
      found that outcomes for people living in the two facilities did not change at
      different rates. These consistent findings suggest that although the assisted
      living and nursing home environments claim to have different philosophies of
      care, health outcome patterns for people living in the two environments were
      similar.

PMID- 10961032
TI  - The effects of outpatient geriatric evaluation and management on caregiver
      burden.
AB  - This study investigated the effects of outpatient geriatric evaluation and
      management (GEM) on informal caregivers' sense of burden. We randomized 568 high
      risk, community-dwelling older adults to receive either GEM or usual care for 6
      months. At baseline and one year later, we assessed the burden experienced by
      their informal caregivers (N = 88). Compared with caregivers of participants in
      the usual care group, caregivers of participants in the GEM group were less than
      half as likely to report increased burden during the one-year follow-up period
      (16.7% vs 38.5%, p = .034). The findings suggest that GEM helps protect the
      informal caregivers of high-risk older people from the increases in burden that
      often accompany advancing age.

PMID- 10961033
TI  - Two transitions in daughters' caregiving careers.
AB  - Daughters and daughters-in-law of presently unmarried elders were studied
      longitudinally, and the data were analyzed to determine how two transitions in
      caregiving status affected the women of the younger generation. One transition
      compared noncaregivers who had become caregivers 1 year later ("caregiving
      entrants," n = 33) with continuing noncaregivers (n = 56) and with veteran
      continuing caregivers (n = 78) over the same period. The second transition
      followed Time 1 new caregivers as they became "new veteran" caregivers (n = 69),
      comparing them with "old veteran" caregivers (n = 189) over the same year. The
      transition to caregiving was marked by a decrease in the care receiver's
      competence and an increase in the amount of care received, but caregiving
      entrants' quality of life did not change significantly over 1 year, as compared
      with either continuing noncaregivers or veteran caregivers. Although longitudinal
      study shows little positive evidence for the wear-and-tear model of caregiving,
      methodological improvements are needed before discarding the hypothesis that
      caregiving erodes mental health.

PMID- 10961034
TI  - Preferences for surrogate decision makers, informal communication, and advance
      directives among community-dwelling elders: results from a national study.
AB  - This study, drawing on a nationally representative sample of community-dwelling
      adults aged 70 and older from the second wave of the Asset and Health Dynamics
      Among the Oldest Old (AHEAD) survey, addresses the need for greater information
      on advance care planning among older adults. Older persons expect to draw on a
      diverse array of persons to make health care decisions for them when they are
      unable to do so, including spouses, when available, as well as younger generation
      members such as children and grandchildren. Completion of advance directives such
      as living wills and durable powers of attorney for health care was more common
      among White respondents than among African American respondents, and among high
      school- and college-educated respondents compared with those with less than a
      high school education. The results suggest the need to develop interventions
      aimed at strengthening knowledge and understanding of advance directives,
      particularly for African Americans and persons with lower levels of educational
      attainment. They further suggest the need for more research on the factors
      related to informal communication between older adults and their family members
      on issues related to advance care planning.

PMID- 10961035
TI  - The effects of interpersonal and personal agency on perceived control and
      psychological well-being in adulthood.
AB  - A theoretical model that links social support with global beliefs in primary
      control and provides a developmental perspective on how normative age-related
      changes alter control beliefs was examined with data from 482 adults aged 18 to
      93. Generalized belief in primary control was hypothesized to have a direct
      positive effect on psychological well-being and to arise from two distinct
      sources: (a) interpersonal agency (obtaining positive ends through interactions
      with others) and (b) personal agency (achieving desired outcomes on one's own
      behalf). Age was believed to affect both types of agency indirectly as a result
      of age-related changes in physical health and emotional support. Although
      physical health was presumed to have a direct positive effect on psychological
      well-being, the effect of emotional support on well-being was mediated by
      interpersonal agency and perceived primary control. Structural equation modeling
      analyses with the EQS 5.4 program revealed good model fit (goodness-of-fit index
      = .98, comparative fit index = .94, root mean square residual [RMR] = .02,
      standardized RMR = .05, root mean square error of approximation = .06) after a
      negative direct path from age to generalized beliefs in primary control was added
      to the a priori model.

PMID- 10961036
TI  - Work history and U.S. elders' transitions into poverty.
AB  - Poverty risks among elders are shaped in critical ways by their work history,
      demographic characteristics, current marital status, and residential context.
      Using 25 years of data from the Panel Study of Income Dynamics, we combined past
      occupation and work history of elders and their spouses with information on
      current marital status and residence to estimate discrete time event history
      models of first transitions into poverty after reaching age 55. Education, work
      history, and preretirement wages contributed to men's and some women's
      probability of becoming poor. Work history remained an important predictor of
      transitions into poverty, even after controlling for preretirement wages and
      human capital. Metropolitan residence was associated with a lower probability of
      making transitions into poverty. This residential difference was not appreciably
      attenuated in three of four elderly subgroups after measures of work history,
      preretirement wages, current life events, and demographic characteristics of the
      elders were included in the models.

PMID- 10961037
TI  - On their own: nutritional self-management strategies of rural widowers.
AB  - In-depth interviews conducted with 12 rural widowers participating in a
      population-based study of nutritional strategies of rural adults 70 years and
      older were analyzed to (a) identify factors that place widowers at risk for
      nutritional problems and (b) understand how rural residence is related to this
      risk. The nutritional strategies that successfully accomplished three groups of
      food-related tasks (food acquisition, food use, and maintaining food security)
      focused on one of three resource domains: self-care, informal support, and formal
      support. Resources that facilitated these nutritional strategies are identified,
      as are those conditions that led to nutritional strategies inadequate to ensure
      food acquisition, food use, and food security. These findings can be used to help
      identify rural elderly widowers who are at nutritional risk.

PMID- 10961039
TI  - The role of family practice in medical school education.

PMID- 10961038
TI  - A model intervention for elder abuse and dementia.
AB  - This article describes a 2-year collaborative project in Cleveland, OH, that
      improved the reporting and management of potential and suspected elder abuse
      situations involving persons with dementia. Educational curricula for cross
      training, screening tools, and referral protocols were developed and tested for
      staff and volunteers in adult protective services and dementia care. A handbook
      for caregivers of persons with dementia was produced that enables caregivers to
      self-identify elder abuse risk and seek appropriate interventions to prevent
      abuse. Project organization, implementation, and evaluation are discussed along
      with strategies for replication in other communities.

PMID- 10961040
TI  - A review of the United Kingdom Prospective Diabetes Study (UKPDS) and a
      discussion of the implications for patient care.

PMID- 10961041
TI  - The cell cycle.
AB  - The cell cycle and the cell cycle control system are the engines that drive life.
      They allow for the processes of cell renewal and the growth of organisms, under
      controlled conditions. The control system is essential for the monitoring of
      normal cell growth and replication of genetic material and to ensure that normal,
      functional daughter cells are produced at completion of each cell cycle. Although
      certain clinical applications exist which take advantage of the events of the
      cell cycle, our understanding of its mechanisms and how to manipulate them is
      infantile. The next decades will continue to see the effort of many researchers
      focused upon unlocking the mysteries of the cell cycle and the cell cycle control
      system.

PMID- 10961042
TI  - Dexamethasone use in adult meningococcal meningitis.
AB  - The use of dexamethasone in the management of bacterial meningitis in adults
      remains controversial. This report illustrates the case of a 27-year-old male
      with severe meningococcal meningitis and meningococcemia who completely recovered
      after receiving antibiotics and dexamethasone. In adults with suspected bacterial
      meningitis, especially in high risk cases, the adjunctive use of dexamethasone
      may be beneficial.

PMID- 10961043
TI  - [Lessons learned from the subjects treated by WAME (World Association of Medical
      Editors)].

PMID- 10961044
TI  - [Epidemiology of sexually transmitted diseases in the mine area of Las Claritas,
      Bolivar State, Venezuela].
AB  - The primordial objective of this study was to carry out an epidemiological
      analysis of sexually transmitted diseases (STD) in terms of sensed morbidity and
      real morbidity in the mining region of "Las Claritas", Bolivar State, Venezuela,
      during the third trimester of 1998. The epidemiological characteristics of time,
      people and place are interlaced, giving a relationship included within the
      Epidemiological Triad, that represents this work's conceptual framework; defining
      both, the determinant and the conditioning factors of the presence of STDs in the
      zone. The clinical interrogatory was partially steered towards the participant's
      sensed morbidity. A mostly feminine population is described (65%), with a low
      scholarly level in the general population and a high index of foreigners among
      the evaluated patients; with 48.72% of stable unions in the interviewees. From
      166 evaluated patients, 27.70% referred to have had some STD episode, being
      syphilis and blenorrhagia the most frequently reported. In the survey, there was
      a general hush concerning the presence of STDs; but, key informants such as the
      medicine retailers, revealed a higher presence of these diseases, which are
      wrongly treated by automedication. These are important results, since they let
      opened a space for the epidemiological evaluation in the zone, in the various
      health, sanitary, environmental and social aspects and mainly, by the
      individual's quality of life expectations.

PMID- 10961045
TI  - [Lupus anticoagulant in preeclampsia and non-proteinuria gestational hypertension
      in primiparous women].
AB  - The purpose of this study was to determine the relationship between the lupus
      anticoagulant and the proteinuric and non-proteinuric Gestational Hypertension in
      primigravids without subjacent pathology. Sixty- five patients with a single
      gestation of twenty or more weeks long were studied. Thirty four patients (Group
      A) were pregnant women with a normal blood pressure. Hypertensive disease
      developed during pregnancy (according to Davey and MacGillivray, classification)
      affected 31 patients (Group B). A test to determine the presence of the lupus
      anticoagulant was performed on all of them, according to the method of the
      diluted Russel viper venom. None of the patients developed any other symptomatic
      subjacent pathology. Fifty-five percent of the Group B patients developed
      proteinuric gestational hypertension (preeclampsia) and forty-five percent of
      them non-proteinuric gestational hypertension. The test to determine the lupus
      anticoagulant was negative in all the patients from both groups. The results
      suggest that the presence of a lupus anticoagulant is unlikely in the proteinuric
      and non-proteinuric gestational hypertension in primigravidas without subjacent
      pathology, therefore it remains as a controversial study issue.

PMID- 10961046
TI  - [Effect of stress electrocardiogram on platelet function, concentration of von
      Willebrand factor and fibrinogen in hypertensive patients and healthy subjects].
AB  - The aim of the present study was to investigate the effect of the treadmill
      electrocardiogram (TMECG) on thrombotic risk factors in hypertensive patients and
      normal individuals. Twenty patients, 10 males and 10 females between 40 and 55
      years of age, were studied and twenty normal persons of matching sex and age were
      chosen as controls. Blood samples were obtained before and immediately after the
      TMECG. Platelet counts and function as well as fibrinogen and von Willebrand
      factor (vWF) levels were determined in each sample. A significant increase in
      platelet number and aggregation with collagen and ristocetin was observed in all
      groups after the TMECG. Fibrinogen and von Willebrand factor levels were also
      significantly increased in all individuals. It is known that platelets play an
      important role in the formation of thrombi and the enhancement in their number
      and activity, in certain circumstances, might favor the development of a
      thrombotic episode. Elevated fibrinogen concentrations are considered an
      independent cardiovascular risk factor. The above changes in patients with other
      predisponent factors for cardiovascular events, such as arterial hypertension,
      enhances the possibility of a vasooclusive episode. It is recommended therefore,
      that before suggesting a physical activity to a hypertensive patient, other
      parameters, such as age, previous training and the existence of other
      cardiovascular risk factors should be considered.

PMID- 10961047
TI  - [Huntington disease. A review].
AB  - Huntington's disease (HD) is a hereditary autosomal dominant neurodegenerative
      disease characterized by motor, cognitive and psychiatric symptoms. It affects
      about 1 in 10,000 individuals. The onset of symptoms typically occurs in the
      third or fourth decade of life, though it may appear at any age. The molecular
      basis of the disease is the expansion of the trinucleotide CAG in the first exon
      of a gene on chromosome four (4p 16.3). This gene encodes the protein huntingtin
      of 3136 amino acids. The mutation of huntingtin produces an expanded stretch of
      glutamine (Gln) residues. This CAG/polyGln expansion has 6 to 39 units in normal
      individuals and 36 to 180 units in HD patients. The normal function of huntingtin
      and the pathogenic mechanisms caused by the expanded polyGln of mutant huntingtin
      remain incompletely characterized. Huntingtin appears to be associated with
      synaptic vesicles and/or microtubules and seems to have an important role in
      vesicular transport and/or the binding to the cytoskeleton. It is thought that
      this protein is important in embryogenesis and that its mutant form alters the
      function of the mitochondrial respiratory chain. The toxic gain of function
      caused by huntingtin could either be an overactivity of the normal function or
      the introduction of a novel function. Its interactions with other proteins could
      lead to an impairment of the cellular function or to its own polymerization to
      form insoluble aggregates. The intraneuronal aggregates could affect gene
      transcription, protein interactions, protein transport inside the nucleus and
      cytoplasm, and the vesicular transport. However, since a dissociation between the
      aggregation of huntingtin and the selective pattern of striatal neuronal loss has
      been demonstrated, it is believed that other properties of the mutant huntingtin,
      like proteolysis and the interactions with other proteins that affect vesicular
      trafficking and nuclear transport, could be responsible for the
      neurodegeneration. On gross examination, 80% of HD brains show atrophy of the
      frontal lobes. A bilateral, symmetric atrophy of the striatum is observed in 95%
      of the HD brains. The mean brain weight in HD patients is approximately 30% lower
      than in normal individuals. Striatal degeneration has an ordered and topographic
      distribution. The tail of the caudate nucleus shows more degeneration than the
      head. The caudate atrophy is associated to a gradual atrophy and neuronal loss in
      other brain regions as the disease progresses. The striatal and cerebral cortex
      projection neurons are much more susceptible to the disease than interneurons. In
      the neostriatum, the levels of GABA, dynorphin and substance P are decreased, but
      the concentrations of somatostatin and neuropeptide Y increase. An impairment of
      energy metabolism in HD and a sensitivity to oxidative stress and to the
      cytotoxic effects of glutamate seem to contribute to the neuronal death in HD. It
      is proposed that melatonin should be assayed in cell cultures and in transgenic
      animals due to its potent antioxidant and free radical scavenger properties.

PMID- 10961048
TI  - Nager syndrome. Problems and possibilities of therapy.
AB  - The congenital Nager acrofacial dysostosis syndrome is presented, and
      possibilities and problems in the treatment of these patients are described. A
      case study of a patient who has been followed from birth to adulthood illustrates
      the surgical/orthodontic course of treatment and its limits.

PMID- 10961049
TI  - Localization of lower right molars in a panoramic radiograph, lateral cephalogram
      and dental CT.
AB  - In this investigation, the radiological status of angular measurements in the
      wisdom tooth area was examined. The angles of the tooth center lines of the
      second and third lower molars (48, 47) to the occlusal plane and to one another
      in 25 orthodontically untreated patients (average age: 16.3 years) were measured
      and compared with angular values of the patients concerned measured in a dental
      CT. The assessment of these 3 radiological documents in an absolute comparison
      revealed closely corresponding angular values. However, the dental CT provided a
      considerably more accurate and, in addition, a three-dimensional topographical
      localization of lower wisdom teeth.

PMID- 10961050
TI  - Contribution to the biological assessment of orthodontic acrylic materials.
      Measurement of their residual monomer output and cytotoxicity.
AB  - The acrylic materials used in orthodontics for the fabrication of removable
      appliances are subjected in the oral cavity to processes of change which
      influence their physical, mechanical and biological properties. It is therefore
      essential that every newly developed material must be judged in terms of its
      clinical value. In the present study, 2 orthodontic cold-cure acrylics, Orthocryl
      and Forestacryl, and 4 orthodontic photocure acrylics, Triad, Wil-O-Dont,
      Odontolux and Lux-A-Tech, were investigated and compared with 2 prosthetic
      acrylic materials: the cold-cure acrylic Palapress and the hot-cure acrylic
      Paladon. The quantity of residual monomers from methyl methacrylate (MAA) or
      urethane dimethacrylate (UDMA) eluted from the sample in a given time after the
      processing was estimated by high pressure liquid chromatography (HPLC). The
      cytotoxic properties of the materials were examined by Mosmann's proliferation
      inhibition test with an established culture of fibroblasts (= MTT test). The hot
      cure acrylic Paladon produced by far the smallest amount of eluted residual
      monomer and the least growth inhibition in the MTT test. The prosthetic cold-cure
      acrylic Palapress achieved significantly better results than the orthodontic cold
      cure materials Orthocryl and Forestacryl. The photocure acrylics released less
      UDMA than did the cold-cure acrylics MMA. In the cell culture test, all the
      orthodontic materials examined were assessed as "slightly cytotoxic"; the
      prosthetic acrylics were graded under ISO-standard 10993-5 as "noncytotoxic".
      After soaking the plastic material in water for 3 days its cytotoxic properties,
      as exemplified by the cold-cure acrylic Forestacryl and the photocure acrylic
      Triad, were reduced, and during the following investigation no more inhibition of
      growth was observed. It was possible to confirm with the tests used that, for
      Triad, it is necessary to carefully remove the oxygen-inhibition layer of the
      photocure acrylic in order to improve the biological properties. The influence of
      the plastic material on fibroblast cultures was assessed, among other methods, by
      the quantity of residual monomers liberated. These were significantly reduced
      after soaking the manufactured substance in water for 3 days. Careful laboratory
      treatment of the photocure acrylics is necessary in order to improve their
      biological properties.

PMID- 10961051
TI  - Torque transmission between square wire and bracket as a function of measurement,
      form and hardness parameters.
AB  - The aim of the study was to investigate the influence of cross section, edge
      geometry and structural hardness on torque transmission between square wire and
      bracket. For this purpose, 5 different brands of stainless steel square wire in 3
      dimensions (0.016" x 0.016", 0.016" x 0.022" and 0.017" x 0.025") were inserted
      into edgewise brackets with a slot size of 0.018" and loaded with different
      torques (1 and 3 Ncm). The slot and wire geometries were analyzed by computer on
      ground specimens before and after loading. In addition, the Vickers hardness and
      micro-hardness of the unstressed and stressed metal surfaces were determined.
      While the slot size was very accurately maintained, the wire dimensions deviated
      downwards by an average of 10%. Torque transmission led to notching and bending
      up phenomena on the bracket slot flanks. A torque loading of 3 Ncm increased the
      torque play of 0.016" x 0.022" wires by 3.6 degrees, and of 0.017" x 0.025" wires
      by 3.7 degrees. In the case of 0.016" x 0.016" wires, an effective torque
      transmission was no longer possible. The average Vickers hardness of the wires
      was 533 kp/mm2, and that of the brackets 145 kp/mm2. The micro-hardness in the
      deformation area of stressed internal slot walls increased with increasing load
      transmission from 204 to 338 kp/mm2. As a result of excessively small wire
      dimensions and plastic deformation of the brackets, a relatively large torque
      play occurs. Deformation and notching in the area of the internal slot walls are
      inconsistent with demands for recycling brackets. A standardization of bracket
      wire systems stating the actual torque play would be desirable.

PMID- 10961052
TI  - Application of bone remodeling theories in the simulation of orthodontic tooth
      movements.
AB  - A numerical model that calculates bone apposition and resorption around a tooth
      root on the basis of bone remodeling theories was developed to simulate
      orthodontic tooth movements. The model was used to calculate different kinds of
      orthodontic tooth movements, that were then compared with the expected movements
      based on clinical experience. For simulation of the movements the root of a
      canine was modeled in an idealized way in the form of an elliptical paraboloid
      and was processed with a finite element program. The finite element model was
      loaded with defined force systems. Two model assumptions were used to calculate
      the bone remodeling process. The mechanical loads firstly in the periodontal
      ligament and secondly in the alveolar bone were taken to simulate the following
      tooth movements: 1. mesial tipping around the center of resistance (force system
      at the bracket: isolated torque MY = 5 Nmm), 2. rotation around the long axis of
      the tooth (MZ = 5 Nmm), 3. uncontrolled tipping around the root tip (FX = 1 N, MZ
      = 5 Nmm), 4. canine retraction (FX = 1 N, MY = -9.5 Nmm, MZ = 5 Nmm), 5. and 6.
      extrusion/intrusion (FZ = +/- 0.5 N, MX = +/- 2.5 Nmm). Comparison with clinical
      experience was performed by calculating the orthodontic tooth movements based on
      the assumption of a fixed position of the center of resistance. It could be
      demonstrated that the numerical model of orthodontic bone remodeling can be used
      to calculate orthodontic tooth movements. However, the results are strongly
      dependent on the model assumptions. The model simulating the bone remodeling on
      the basis of the loading of the periodontal ligament delivers results that are in
      very good accordance with the biomechanical assumptions of the position of the
      center of resistance. However, marked side effects occurred with the second
      model, especially in the simulations of uncontrolled tipping, translation and
      intrusion/extrusion. Clinically, these side effects cannot be observed.

PMID- 10961053
TI  - Lingual orthodontics (Part 3): Intraoral sandblasting and indirect bonding.
AB  - Bracket loss is a severe complication in the course of orthodontic treatment,
      especially when using lingual appliances. High adhesive strength between bracket
      and tooth is therefore an important requirement for the successful integration of
      lingual orthodontics into everyday practice. The present article examines the
      influence of intraoral sandblasting prior to etching on the adhesive strength of
      indirect bonding. The shear bond strength of 20 cylinders made of composite were
      measured 24 hours after these had been bonded onto the enamel of bovine teeth.
      The enamel was prepared by sandblasting (Microetcher, 50 microns Al2O3) for 3
      seconds prior to bonding, followed by 30 seconds of enamel etching with 37%
      phosphoric acid. Twenty specimens were tested without sandblasting in the control
      group. The results show that intraoral sandblasting prior to etching can
      significantly (p < 0.001) increase the adhesive strength between enamel and
      bonding material. Thus intraoral sandblasting is an integral part of the indirect
      bonding record described in the second section of this article.

PMID- 10961054
TI  - [The SIAARTI in comparison to other scientific societies in Italy and in Europe.
      A policy for continued improvement of quality].

PMID- 10961055
TI  - Immune-imbalance in sepsis.

PMID- 10961056
TI  - [Laryngeal mask vs tracheal tube in pediatric anesthesia in the presence of upper
      respiratory tract infection].
AB  - BACKGROUND: The aim of this report is to assess the incidence of postoperative
      respiratory complications in patients recently suffering from inflammation of the
      upper respiratory tract in whom a LMA or an uncuffed orotracheal tube have been
      used. METHODS: Four hundred patients were enrolled aged 6 months to 12 years
      undergoing general anaesthesia for elective body surface surgery with insertion
      of the LMA (group M) or the uncuffed tube (group T). Acute inflammation of the
      upper airways (URI) was assessed, defined by the presence of at least two of the
      following symptoms, rhinorrhea, coughing, pharyngodynia, disphony, fever,
      malaise. The appearance of post-surgical adverse respiratory events (ARE), such
      as laryngospasm, stridor, disphony, excessive coughing was detected. Patients
      were divided into four groups in relation to the management of the airway and the
      presence or otherwise of URI (M URI, M NO URI, T URI, T NO URI). RESULTS: In NO
      URI patients, the presence of ARE was 9.6% in the M and 36.9% in the T group (p <
      0.001); in URI patients, these figures were respectively 31.5% and 73.9% (p <
      0.001). CONCLUSIONS: The frequency of ARE increases significantly in URI patients
      with both LMA and the tracheal tube, but with the former is far lower than with
      the latter. Despite the appearance of only minor and transient complications, it
      is confirmed that the tracheal intubation is an additional risk factor as a
      result of the mechanical airway simulation. In recent URI, it would seem
      appropriate to avoid tracheal intubation, if possible, preferring the LMA.

PMID- 10961057
TI  - [Tetanus. Physiopathology and intensive care treatment].
AB  - BACKGROUND: Tetanus as a topic illness is underlined on the basis of the
      increased cases as well as the appearance of new populations at risk of
      infection. The tetanospasmins of mechanism action is stressed in order to
      evaluate the etiopathogenetic role of common therapies as well as the new ones.
      Ten cases of serious infection personally observed are analysed. METHODS: The
      case records of ten tetanus patients treated in our Intensive Care Unit between
      1986 and 1997 have been retrospectively analysed. The prognosis correlated to the
      seriousness of the case. The most common clinical symptoms on admission were
      trismus and dysphagia (100% of patients). In 70% of cases, the illness was
      considered serious enough to warrant the use of neuro-muscular blockers and
      controlled ventilation. Among the complications observed pulmonary problems had
      the highest incidence (90%), followed by cardio-vascular ones (80%). Respiratory
      infections were the most frequently observed (9 patients). Autonomic dysfunction
      was a constant feature in patients with severe forms of the illness. RESULTS: The
      observed mortality rate was 30%. It was higher in males at the extremes of the
      age range. CONCLUSIONS: In the light of the survival results as well as the most
      recent literature data, guidelines for the approach of serious tetanic patients
      are outline. It is underlined that therapy effectiveness is higher when from
      being a symptom therapy it becomes an etiopathogenetic therapy.

PMID- 10961058
TI  - The hemostatic balance after plasma-exchange transfusion in myasthenia Gravis.
AB  - BACKGROUND: To study the effects of plasma-exchange on removal and recovery of
      haemostatic factors and inhibitors using albumin or PPS as replacement fluid.
      METHODS:  DESIGN: Prospective, noninterventional study. SETTING: Medical
      intensive care unit of a university hospital. PATIENTS: The study included 11
      consecutive patients with Myasthenia Gravis, whose haemostatic parameters were
      normal before plasma-exchange. INTERVENTIONS: Plasma coagulative factors and
      inhibitors were studied before at the end of and 24 hours after each exchange.
      RESULTS: Immediately after exchange plasma coagulation factors and inhibitors
      evaluated were reduced, except for factor VIII; 24 hours later only fibrinogen
      was significantly decreased; D-Dimer was not found increased; the platelets,
      after exchange, were at normal levels. CONCLUSIONS: Our data show a parallel
      lowering of haemostatic factors and inhibitors after plasmapheresis using
      material devoid of coagulation factors as replacement, this explains the absence
      of hemorrhagic or thrombotic complications. So we think that careful monitoring
      of coagulation during plasma-exchange is not useful.

PMID- 10961059
TI  - [Post-intubation subglottal stenosis in children: risk factors and prevention in
      pediatric intensive care].
AB  - BACKGROUND: Endotracheal intubation (EI) may result in significant injury to the
      larynx and trachea; subglottic stenosis is the most dangerous consequence of this
      injury in the pediatric age. It is well known that there are potential risk
      factors for post-intubation subglottic stenosis, and namely the underlying
      disease requiring EI, the age and body weight at EI, the duration and number of
      EI, the absence of sedation and the occurrence of infectious, hypotensive or
      hypoxic events during the period of EI and the traumatic EI. On the basis of our
      data an attempt is made to understand which factors are more important in the
      pathogenesis of this complication and whether post-intubation subglottic stenosis
      is a preventable complication of EI in children. METHODS: The clinical records of
      32 out of 35 children with post-intubation subglottic stenosis referred to our
      institution because of this complication in the period 1990-1997 (8 years) have
      been examined. Three children were excluded from the study because of partial
      data. Our surgical division is specialized in the diagnosis and the management of
      pediatric laryngotracheal diseases. The diagnosis was confirmed by
      videolaryngotracheoscopy under general anesthesia and by computerized tomography
      or magnetic resonance imaging in 10 children whose tracheal stenosis was
      critical. The degree of the stenosis was determined according to Cotton's
      classification. RESULTS: The analysis of our data confirms that post-intubation
      subglottic stenosis is a more frequent complication in infants and particularly
      in low birth weight infants. It occurred after long lasting EI, but after short
      lasting EI too. Many of the children observed had their trachea intubated several
      times during their illness and many EI were traumatic. Sedation during EI was
      only seldom took into account by pediatric intensivists. CONCLUSIONS: Prevention
      of post-intubation subglottic stenosis is possible through a better management of
      the EI and of the child with a tracheal tube. Sedation of intubated children and
      skill in the EI technique and in the tube size selection are very important. Many
      intubations can be avoided with a better attention to the tube fixation and to
      extubation criteria. Some children at high risk for this complication can be
      identified.

PMID- 10961060
TI  - [Cardiac rupture in thoracic trauma].
AB  - Thoracic trauma frequently involve damage to the cardiac structures and in the
      worst cases, the progressive degeneration and necrosis of the damaged tissue lead
      to cardiac rupture. The high mortality resulting from cardiac tamponade requires
      the prompt execution of diagnostic tests to provide as much useful information as
      rapidly as possible in order to start immediate therapy. A case of cardiac
      rupture manifested by the onset of atrial fibrillation in a patient admitted to
      Intensive Care after a car accident is described. The scarce significance of
      objective examination, the aspecific nature of chest X-ray and ECG alterations
      prompted the execution of a more thorough diagnosis. Transthoracic and
      transesophageal ultrasonography are both minimally invasive and highly specific:
      in a short time, not only did they confirm cardiac rupture, but they also
      focalised the site of the lesion, thus allowing a more targeted and rapid
      surgical approach. The relative frequency of cardiac lesions following closed
      thoracic trauma, the lack of incontrovertible signs and symptoms of late cardiac
      rupture, and the extreme severity of its clinical consequences argue in favour of
      using specific and sensitive diagnostic tests that can not only exclude or
      ascertain the presence of these lesions, but also allow subsequent serial
      controls aimed at diagnosing late cardiac ruptures.

PMID- 10961061
TI  - [Guidelines in clinical practice. Legal considerations].
AB  - The paper analyses the role and implications of the application of these
      guidelines from a legal point of view. After an introduction based on the legal
      concepts of the causal nexus and guilt in jurisdiction, the authors highlight the
      main arcas of influence that these guidelines can have on evaluations of a
      torensic nature. In jurisdictional terms, the first step in the evaluation of
      medical conduct is to reconstruct the causal nexus between the doctor's conduct
      (active or omissive) and the injury/death in question. The identification of the
      causal nexus is based on the application of the laws of probability according to
      which it is possible to affirm, with a reasonable margin of logical and rational
      plausibility, that a given conduct is the causal condition of a particular
      harmful event. With this in mind, the guidelines assume the role of law of
      probability in the sense that their adoption, depending on an evaluation of the
      probabilistic regularity of the causal series, would have prevented the
      occurrence of the injury/death that is the object of the legal inquiry. Another
      essential step in the jurisdictional process, is the evaluation of guilt. Bearing
      in mind that the evaluation of guilt is by definition linked not to the actual
      doctor in question, but to an abstract model of a doctor and namely the knowledge
      and skills that a doctor is expected to possess, it can be seen that the adoption
      of these guidelines may facilitate this evaluation. The application of the
      guidelines would represent compliance with the ordinary conditions of knowledge
      and skill expected of a doctor to which should be logically added the need for an
      adequate motivation for any deviation from the indications expressed in the
      guidelines. In conclusion, the main influences of these guidelines for the doctor
      patient relationship are evaluated, together with the role that these guidelines
      may play in terms of patient information and the informed consent given by the
      latter.

PMID- 10961062
TI  - [Guidelines in clinical practice. Bioethical considerations].
AB  - The adoption of guidelines in clinical practice raises questions that can be
      answered against a background in which professional conduct is compared with
      deontology, law, and the specific sociocultural context and health policies of
      institutions. In the scientific community, doubts are raised regarding the
      relationships between the general recommendations laid down in the Guidelines and
      the specific nature of every clinical condition; between the "duty of adhering"
      to Guidelines and the doctor's autonomy, as well as between the adoption,
      discrepancy and non-adoption of Guidelines and the juridical evaluation of
      medical liability. The information and individual consent of patients and
      citizens is of particular importance both with regard to clinical procedures and
      choices of allocation. In the light of these comments, the authors conclude that
      Guidelines should not be reduced to a form of automated procedure lacking any
      responsibility, but should represent a correct synthesis between the objective
      nature of scientific findings, the subjective condition of the patient and the
      doctor's autonomy. The application of correctly formulated Guidelines shared by
      the community means acting in such a way that the "right to health" and "freedom
      of treatment" can be exercised in respect of shared bioethical principles based
      on beneficence, autonomy and justice.

PMID- 10961063
TI  - [Environmental detection of anesthetic gases during inhalation with COPA].

PMID- 10961064
TI  - [Infections in intensive care].

PMID- 10961065
TI  - Cochlear implants for completely deaf patients, scientifical background--results-
      perspectives.

PMID- 10961066
TI  - [Value of intraoral ultrasonography in diagnosis of tonsillar tumors].
AB  - Aim of the study was to establish clinical utility of intraoral ultrasonography
      in diagnosis of tonsillar tumours in respect to its magnitude, location,
      histological structure, presence of satellite lesions and furthermore compare
      results obtained by endoral to transcutaneous ultrasonography. 64 patients with
      tonsillar tumour entered the study. Endoral ultrasonography was performed by
      probe UST-937 Convex 5 MHz. CONCLUSION: Endoral ultrasonography is very efficient
      in exact tumour localisation and correlation between endoral ultrasonography and
      intraoperative assessment of T tumor is statistically significant.
      Ultrasonography is sensitive in recognition of satellite lesions. In the case of
      planoepithelial cancer, malignant lymphoma and inflammatory process very
      characteristic features of tumor can be described. Endoral ultrasonography is
      better then transcutaneous in tonsillar tumours diagnosis.

PMID- 10961067
TI  - [Laryngeal microsurgery in materials of Woiewodzki ENT department in Kalisz].
AB  - Basing on literature and own experience authors have presented possibilities and
      advantages this method. During 1994-1997 3239 patients were hospitalized, 249
      because of larynx diseases. 88 (35.34%) from them were operated by Kleinssaser
      tool kit with control by surgical microscope. Between these patients in
      histological examination were found in 30 patients--changes of hypertrophy, in 23
      patients--polypus vocal fold, in 17 patients cancer of larynx--early shape, in 12
      patients--vocal nodulus and 2 patients--Reincke oedema, 2--laryngeal papillomas
      and 2--cysts of larynx. Patients with cancer of larynx were treated by partial
      laryngectomy. Other patients had return full function of larynx.

PMID- 10961068
TI  - [pH of fluid collected from middle ear in the course of otitis media in
      children].
AB  - In course of the study, pH of secretions taken during operation from middle ear
      of 112 children suffering OMS was examined. Samples of serous, mucous and serous
      mucous secretions were collected. Values of pH were determined using 6.4-8.0 and
      8.2-10.0 test-papers produced by E. Merck. pH of all samples was alkaline. Mean
      value of pH of mucous and serous-mucous secretion was higher (8.55 and 8.33,
      respectively), than serous secretion (7.92). Positive correlation between the age
      of children and pH of secretions was noticed.

PMID- 10961069
TI  - [Diverticulectomy for hypopharyngeal diverticula].
AB  - In the Otolaryngology Department of Pomeranian Medical Academy in Szczecin since
      1980-1999 14 patients with pharyngo-oesophageal diverticulum were diagnosed and
      treated. Diverticulectomy was performed in 13 cases. Not dangerous complications
      during the postoperative period were observed in four cases. In one case it was
      abscess in postoperative wound, in two cases fistula to soft tissue in
      prevertebral region and in one case paresis of vocal cord. In all these cases
      complications retreated spontaneous. We had not observed any recurrence of
      pharyngo-oesophageal diverticulum. In 6 cases control radiological examination
      was performed (from 2 months to 7 years after surgical treatment). In all cases
      we hadn't observed any recurrence of diverticulum. In one case radiological
      examination revealed diverticulosis in all digestive system. But even in this
      case we hadn't found recurrence of Zenker's diverticulum. In this paper we
      discuss other methods of treatment of pharyngoesophageal diverticulum.

PMID- 10961070
TI  - [Antioxidant enzymatic activity in blood of patients with chronic hypertrophy of
      the maxillary sinuses and larynx and the carcinoma of the larynx].
AB  - The aim of the work was the examinations of antioxidant enzymatic activity in
      blood of patients with chronic hypertrophic of maxillary sinusitis (15 patients)
      and laryngitis (10 patients), and carcinoma of larynx (7 patients) in comparison
      with healthy persons (15). The enzymatic activity of superoxide dismutase in
      blood (method of Misra and Fridovich), katalase (method of Beers and Sizer) and
      malonyl dialdehyde (method of Placer) were evaluated. The obtained results
      pointed at significant reduction of antioxidant enzymatic activity against the
      oxygen species generation in blood of patients with chronic hypertrophic of
      maxillary sinusits and laryngitis and mainly with the carcinoma of larynx (in
      comparison with healthy persons). At the same patients observed the significant
      growth of peroxydation lipoid and disturbances of function of cells the human
      body.

PMID- 10961071
TI  - [Evolution of vestibular schwannoma: radiological evaluation].
AB  - Objective evaluation of natural history of vestibular schwannomas can be
      performed based on the modern radiological investigations, mainly MR. This study
      included 7 vestibular schwannomas. The average observation period was 28 months.
      Tumor growth was calculated based on the comparison of volume on the first and
      subsequent MR image using a special dedicated software. All tumors in this study
      were growing. The average growth rate was 143 mm3/month. Among 7 primarily
      observed tumors, 4 schwannomas were already removed surgically. The remaining 3
      tumors are still observed. The authors pointed out that longer were the
      radiological observations of vestibular schwannomas greater was the conviction
      about progression of majority of these tumors.

PMID- 10961073
TI  - [Factors deciding on attending hard-of-hearing or deaf children schools].
AB  - The aim of this work was to elucidate the deciding factors of selection of pupils
      to hard-of-hearing and deaf children schools. The material consisted of 138 hard
      of-hearing and 170 deaf school children, aged from 6 to 16 years. The hard-of
      hearing children revealed severe and profound hearing impairments, passed through
      on the average two and half years of hearing and speech rehabilitation before
      entering to the school and used continually all day their hearing aids. In
      contrast the deaf children speech and hearing rehabilitation have had only 30% of
      them and 60% of these children never used the hearing aids. Statistically more
      pupils in the deaf group derived from the deaf families.

PMID- 10961072
TI  - [Analysis of aromatic DNA adducts in oral cavity and pharyngeal cancer].
AB  - An exposure to tobacco smoke carcinogens is followed by an interaction of
      chemical carcinogens with DNA molecule resulted by the formation of carcinogen:
      DNA adducts. The study subjects were 40 oral and pharyngeal cancer patients with
      primary tumours diagnosed as squamous cell carcinoma. The biological samples
      purchased for analysis included tumour biopsy, the surrounding tissue
      (histopathologically recognised as non-malignant) and peripheral blood
      leucocytes. For DNA adducts analysis first DNA was isolated using phenol
      detergent extraction followed by 32P-postlabelling assay including P1 nuclease
      enhancement. Aromatic DNA adducts were found in all studied tissues. The average
      levels of DNA adducts in tumour and non-tumour tissues were found higher than in
      leucocytes. Biopsies from pharynx contained higher levels of DNA adducts than
      from oral cavities. Confounding effect of tobacco smoking and alcohol consumption
      on DNA adducts level was observed but it has not reached statistical
      significance. Formation of DNA adducts was not depended on such factors as
      patients age, sex, pulmonary tuberculosis, cancer progression (TNM),
      environmental pollution and mechanical irritation.

PMID- 10961074
TI  - [Speech understanding in patients after stapedectomy (early results)].
AB  - The authors report a comparison the parameters of the speech audiometry (SRT,
      SDS) and the hearing level before and after stapedectomy in patients to and over
      50 years of age. 87 patients (107 ears) with otosclerosis were undergoing
      stapedectomies on the local anaesthesia via a transcanal approach. Control
      examination was performed 21-30 days postoperatively on average. Average
      improvement of the hearing level for the speech frequency (PTA) was better in
      patients to 50 years of age (29.5 dB) than in group over 50 years of age (26.5
      dB). Parameters of speech audiometry (SRT and SDS) post stapedectomy were better
      in patients over 50 years of age.

PMID- 10961076
TI  - [The voice evaluation after vertical hemilaryngectomy].
AB  - The basic parameters of voice were estimated in 24 patients after vertical
      hemilaryngectomy. The results show deterioration of voice quality, but its social
      efficiency is still enough.

PMID- 10961075
TI  - [The recurrent laryngeal nerve paralysis as a complication after thyroid
      surgery].
AB  - The authors have presented results of otolaryngologic and phoniatric examination
      of 504 patients after thyroid surgery. 39 patients (7.74%) with recurrent
      laryngeal nerve paralysis were qualified for thorough phoniatric investigation.

PMID- 10961077
TI  - [Primary malignant melanoma of the larynx].
AB  - Primary malignant melanoma of the larynx is very rare. The case of larynx
      malignant melanoma in 71-years old men is presented. Hoarseness was the main
      complaint that encouraged the patient to visit a doctor. The patient was heavy
      smoker, he had been smoking 40 cigarettes for the last 50 years. He used to drink
      about 200 ml of pure alcohol per day. In the direct laryngoscopy gluish had
      cyanotic tumor, extending to the true vocal cord, ventricle, ventricle fold and
      subglottic space was seen. Enlarged cervical lymph nodes, laterally to the main
      vessels were found both in palpation and in US examination. Total laryngectomy
      and neck dissection was performed. The histological examination of surgical
      specimen revealed; Malignant melanoma. Metastases in the lymph nodes. Neoplastic
      infiltration of the nodal capsule. The patient was admitted to the complementary
      radiotherapy. At the moment the follow up in outpatient. The article contains the
      review of literature concerning the diagnosis, treatment and prognosis in cases
      of laryngeal malignant melanoma.

PMID- 10961079
TI  - [Isolated sphenoiditis treated with endoscopic surgery in a child].
AB  - Isolated sphenoiditis in childhood is a rare entity which is often very difficult
      to diagnose with conventional techniques. The authors present a case of
      sphenoiditis in nine years old boy, where chronic rhinitis and persistent
      cephalqia where the main symptoms. The diagnosis was made on the base of computed
      tomography and nasal endoscopy. Because of lack of effect after pharmacological
      treatment the child was submitted to endoscopic surgery--sphenoethmoidectomy,
      which resulted it total recovery. The diagnosis, indications to computed
      tomography of paranasal sinuses in children, options of both conservative and
      surgical treatment and possible complications of the diseases are discussed.

PMID- 10961078
TI  - [Intracranial complication of sinusitis in a 18-year old patient].
AB  - We have described a case of intracranial complications, which were caused by
      acute inflammation of maxillary sinus. In our patient we observed the development
      of multilocular intracranial abscesses located in left temporal lobe. However
      intracranial complications of sinusitis are rare, but they are still a serious
      problem that results in high mortality. The dominant features were: nighttime
      headache, fever, amnestic aphasia. The patient was treated surgically--utilizing
      traditional operation Caldwell-Luce'a. A conservative treatment was administrated
      during a long period including high-doses of i.v. antibiotics. This kind of
      patients require an interdisciplinary approach--radiological, neurosurgical and
      otolaryngological. The diagnosis was made with the aid of X-ray, CT-scan and
      cerebrospinal fluid examination. In spite of very intensive treatment the patient
      was unconscious one week. Her condition improved in the third week of her
      admission. CT-scanning carried out in first week showed brain infection.
      Repetition of Ct-scans of the head evidenced progression of disease by forming
      multiple abscesses in left temporal lobe excluding any neurosurgical treatment.
      Finally the patient's condition improved in the third week of her admission. She
      was discharged after six weeks of treatment without cranial nerve palsies.
      Amnestic aphasia lasted next six months.

PMID- 10961080
TI  - [Osteochondroma of the larynx].
AB  - Benign cartilaginous tumours of the larynx and trachea are rare. The most common
      is chondroma, and only 6 cases of osteochondroma of the larynx have been reported
      in the world literature. We present a case of 74 year's old woman with
      osteochondroma of the right arytenoid cartilage. This is followed by a review of
      the literature, diagnostic evaluation and surgical management.

PMID- 10961081
TI  - [A contribution to the etiology of objective tinnitus: the case of arteriovenous
      fistula between the superficial artery and external jugular vein].
AB  - The authors have presented a very rare case of vascular anomaly in 51-years old
      female with an arteriovenous fistula between the frontal branch and parietal
      branch of superficial temporal artery and external jugular vein with
      simultaneously haemangioma cavernosum of temporal region. The clinical
      manifestation and the diagnosis of this anomaly are discussed with particular
      stress laid on the role of carotid arteriography which demonstrated the presence
      of this abnormal arterio-venous communication. Surgical treatment and its results
      are discussed also. The results of diagnostic and therapeutic procedures were
      compared with cases described in the literature.

PMID- 10961082
TI  - [A rare case of the thyroid tissue in the right carotid triangle].
AB  - Authors have described a rare case of split of the thyroid tissue in the right
      carotid triangle in 41 years-old-man. They lay stress on difficulty with making
      right preoperative diagnosis. A growth in the right carotid triangle was
      surgically excised, and the microscopic examination of the specimen revealed
      thyroid tissue with collide goiter. Because this entity cannot be clinically
      distinguished from the others neck tumors, split of the thyroid tissue should be
      considered in the differential diagnosis.

PMID- 10961083
TI  - [Possibility of the achieving of the therapeutic gain in radiotherapy of head and
      neck cancer].
AB  - In nowadays development in radiotherapy head and neck cancers has been achieved
      step by step in 3 main fields: technological, radiobiological and general
      strategy of oncological treatment. One of the most important technical changes
      are: the introducing of three dimensional treatment planning (3 DCRT) system and
      application of new radiological imaging methods (CT, MRI) in treatment planning
      with a computer technology calculation of dose distribution. From the
      radiobiological point of view a very important fact has been to distinguishing
      two kinds of tissue (acute and late reacting tissue) which response depends on
      change in fraction dose. It has given the theoretical basis to clinical trials of
      new methods of fractionation (hyper-, accelerated hyperfractionation). The
      dynamic development of surgery and chemotherapy have established a new place for
      radiation therapy in the complex treatment of tumours (adjuvant, elective,
      concomitant treatment). It has been established that in advanced tumours, the
      first modality of treatment is surgery in conjunction with postoperative
      radiotherapy. Routine application of chemotherapy in head and neck cancer is
      still controversial with exception of radiochemotherapy of nasopharyngeal cancer,
      particularly in cases of lymph nodes metastases.

PMID- 10961084
TI  - ["Oto" -- the episode in the strange world of Vincent van Gogh].
AB  - The author described briefly life of Vincent van Gogh, particularly performed
      episode of ear's cutting.

PMID- 10961085
TI  - [Otolaryngologist and his patient].

PMID- 10961086
TI  - [Clinical use of rhinomanometry in the evaluation of nasal congestion surgery
      treatment results].

PMID- 10961087
TI  - [Balance disorders in hearing impaired children].

PMID- 10961088
TI  - [Report from the conference of the Ukranian society of otolaryngology in Lvov].

PMID- 10961089
TI  - [Report from the international congress "Advances in treatment of head and neck
      cancers: what are the challenges in the third millennium?" Brussels, December 3
      4, 1999].

PMID- 10961090
TI  - [Report from the 4th After-congress Symposium on the palatine and laryngeal
      tonsils in Plzn, Czech Republic, November 5-7, 1999].

PMID- 10961091
TI  - [Report from the International symposium "Multidisciplinary treatment in
      malignant paranasal tumors", Mediolan, October 7-8, 1999].

PMID- 10961092
TI  - [Report from scientific conference of the European Society of Otolaryngology
      (ESO) (2nd Congress of the ESO, September 23-26, 1998, Rome, Proceedings of the
      ESO, October 9-10, 1999, Graz)].

PMID- 10961093
TI  - Importance of lipoprotein metabolism parameters in the clinical and angiographic
      severity of coronary artery disease.
AB  - Coronary artery disease that is clinically and angiographically significant is
      associated to important biochemical parameters with direct interference in
      lipoprotein and apoprotein metabolism. The purpose of our study was to evaluate
      the importance of several lipoprotein metabolic parameters in the clinical and
      angiographic severity of chronic coronary artery disease. In a population with
      the diagnosis of ischemic coronary artery disease, we assessed the degree of
      angiographic (single- versus multivessel disease) and clinical (C.C.S. I-IV
      classification) severities. In each patient, we determined the value of total
      cholesterol, triglycerides, HDL and LDL cholesterol, HDL 2 and 3, apoprotein AI
      and B, lipoprotein (a), anti-phospholipid antibodies and C reactive protein. Our
      results showed that some parameters were significant in the comparison between a
      normal group and the global coronary artery disease population, such as the value
      of total cholesterol, HDL cholesterol, HDL 2, apoprotein AI and B lipoprotein (a)
      and anti-phospholipid antibodies. In the distinction of coronary artery disease
      subgroups, in relation to C.C.S. < or = 2 and > or = 3 classes, some factors
      could be discriminated, such as HDL cholesterol, HDL 2, total cholesterol/HDL,
      lipoprotein (a), anti-phospholipid antibodies and C reactive protein. In the
      distinction between classes C.C.S. < or = 2 and AMI, the levels of triglycerides,
      HDL cholesterol, HDL 2, total cholesterol/HDL, lipoprotein (a) and anti
      phospholipid antibodies were significant. In the division between single vessel
      versus multivessel coronary artery disease we found significant values of HDL
      cholesterol, HDL 2, total cholesterol/HDL, apoprotein AI, lipoprotein (a), anti
      phospholipid antibodies and C reactive protein. In conclusion, our present study
      endorses the clinical role of lipids and plasma lipoproteins in the determination
      of several cardiovascular risk factors, but introduction of new parameters such
      as lipoprotein (a) and the anti-phospholipid antibodies can be very useful for a
      better and global understanding of the pathophysiological processes and
      distinction of higher risk subgroups for extension and degree of severity of
      ischemic coronary artery disease.

PMID- 10961094
TI  - Acid phosphatase, genetic polymorphism and cardiovascular risk factors in a
      pediatric population.
AB  - BACKGROUND: Although the clinical expression of cardiovascular disease usually
      occurs in adulthood, it is unanimously accepted that atherosclerosis begins in
      the pediatric age. Because of the early onset of the disease, it is of great
      importance to screen for major risk factors since pre-school age, especially in
      risk families. Recent investigations have shown a great interest not only in
      studying the classic risk factors, but also in the evaluation of oxidative stress
      and the main antioxidant defense systems. The major cause of this interest is the
      knowledge of the deleterious effect of reactive oxygen species on lipids, the
      endothelial membrane of arteries and, finally, on the occurrence of
      cardiovascular disease. POPULATION AND METHODS: 51 children of both genders, aged
      9-12 years, randomly selected from a rural community, were observed. A possible
      association between low molecular acid phosphatase genetic polymorphism of the
      erythrocyte and the prooxidant status markers (epinephrine oxidase and low
      molecular protein phosphotyrosine phosphatase from the erythrocyte), some
      enzymatic systems of the body antioxidant defense (transmembranar reductase of
      ferricyanide and metahemoglobin reductase) and finally some intermediate
      phenotypes of cardiovascular disease (lipid profile and blood pressure) were
      studied. RESULTS: The study of prooxidant status markers and antioxidant enzymes
      shows significant differences for acid phosphatase and epinephrine oxidase
      activities in relation to low molecular acid phosphatase genetic polymorphism,
      the highest values observed being in those homozygous to the B allele (p < 0.05).
      The inter-relation study between variables showed, among other things, a
      significant inverse correlation between acid phosphatase and transmembrane
      reductase and a direct correlation between apolipoprotein B, acid phosphatase and
      metahemoglobin reductase. A positive family history for cardiovascular disease
      also showed a direct and significant correlation to total cholesterol, LDL
      cholesterol and apolipoprotein B. CONCLUSIONS: The polymorphic variants of low
      molecular acid phosphatase and protein phosphotyrosine phosphatase with greater
      activity are strongly associated, not with the classic parameters of
      cardiovascular risk factors, but with oxidative stress indicators, such as low
      molecular protein phosphotyrosine phosphatase and epinephrine oxidase. Family
      history indicators of cardiovascular risk are clearly associated, since early
      ages, to some conventional risk factors, such as lipid profile and blood
      pressure.

PMID- 10961095
TI  - Prevalence of cardiovascular risk factors in a rural population between 25 and 44
      years old.
AB  - OBJECTIVES: The objective of this study was to evaluate the prevalence of the
      following cardiovascular risk factors, in the 25 to the 44 year age group, in
      persons attending the Goes Health Center: hypertension, high blood cholesterol,
      obesity, smoking and family history of coronary disease. METHODS: 340 individuals
      were selected, for random sample stratification by sex and age groups. They were
      summoned by mail to come to the Health Center for an evaluation of the factors
      studied. Hypertension was defined if systolic blood pressure was > or = 140 mmHg
      and/or diastolic arterial pressure was > or = 90 mmHg and/or if the participant
      was currently under therapy. High blood cholesterol was defined if the
      determination made at the time with a strip-test "Accutrend Cholesterol" was > or
      = 200 mg/dl and/or under specific therapy. Obesity was defined as a body mass
      index > or = 30 kg/m2. Tobacco consumption was defined as an affirmative reply to
      the question "Do you currently smoke?". Previous family history of coronary heart
      disease was defined as an affirmative reply to the question "Do you know of
      anybody in your family who has died or suffers from coronary disease?". RESULTS:
      The global prevalence of hypertension, high blood cholesterol, obesity, smoking
      and previous family history of coronary heart disease was of 20.3%, 32.1%, 11.8%,
      21.5% and 26.8%, respectively. There was an association of risk factors in 22.3%.

PMID- 10961096
TI  - [Role of surgery in the treatment of severe congestive heart failure].
AB  - Patients with severe congestive heart failure which is not reversible by therapy
      and caused by mechanical abnormalities that are not surgically correctable,
      generally constitute desperate cases in which surgical intervention is only
      palliative. Currently, only transplantation can be considered an adequate mid
      term therapy, while cardiomyoplasty and ventricular reduction (Batista) have not
      evolved as viable alternatives. The former has not yielded satisfactory results
      and the experience with the latter is still too short, although the short term
      results also appear discouraging. The shortage of available organs for the number
      of patients on the waiting list and the rejection and infection phenomena, which
      remain the main difficulties with transplantation, may be overcome in the not too
      distant future. Finally, the artificial heart will almost certainly be an
      alternative, but it may, eventually, be overthrown by xenotransplantation.

PMID- 10961097
TI  - [Atrial fibrillation: current trends].
AB  - The author analyses the current relevance of atrial fibrillation (AF), an
      arrhythmia no longer viewed as a benign situation, being the first arrhythmic
      cause of hospitalisation. New data related to the conversion of this arrhythmia
      to sinus rhythm is reviewed, namely internal atrial defibrillation with low
      energy shocks and the efficacy of new drugs such as ibutilide. The current role
      of transesophageal echocardiography in permitting a shorter scheme of
      anticoagulation before the DC shock is also reviewed. About the importance of
      maintaining sinus rhythm, the author mentions new data from the Framingham Study
      showing that AF is an independent predictor of mortality. Attention is drawn to
      the important role of AF duration before cardioversion, since an "electrical
      remodeling" does occur, quickly reducing the probability of maintaining sinus
      rhythm. Concerning the limitations of pharmacological therapy, the author
      mentions the AFFIRM study that, in a few years, will hopefully solve the
      controversy concerning the best strategy--maintenance of sinus rhythm versus rate
      control. Also concerning pharmacological therapy, the author mentions two trials
      suggestive of the efficacy of amiodarone and dofetilide in AF patients with
      congestive heart failure. Regarding non-pharmacological options, reference is
      made to recent advances in surgery of AF and to the search for more simplified
      operative procedures to reduce intervention risks and duration. To overcome the
      difficulties in reproducing the maze operation with catheter ablation, new
      alternatives have appeared, such as energy application inside the pulmonary
      veins, known as the source of most ectopic atrial beats that trigger AF episodes.
      The author concludes that since AF is a heterogeneous entity, different therapies
      must exist, but the pharmacological approach will maintain a central role and non
      pharmacological therapies should be used as an alternative in refractory cases.

PMID- 10961098
TI  - [Isolated non-compaction of left ventricular myocardium].
AB  - Noncompaction of the ventricular myocardium, also known as "spongy myocardium",
      is a rare congenital abnormality resulting from an arrest in the normal
      endomyocardial embryogenesis. The echocardiographic findings consist of multiple,
      prominent myocardial trabeculations and deep intratrabecular recesses in
      communication with the left ventricular cavity. This entity is a not well known
      cause of dilated cardiomyopathy. Some cases were described as X-linked familial
      forms. We report the clinical case of a 13-year-old female patient with severe
      left ventricular disfunction, a very trabeculated left ventricle on
      echocardiography and two admissions in class IV heart failure.

PMID- 10961099
TI  - Acute myocardial infarction in a young patient with metastized non Hodgkin's
      lymphoma.

PMID- 10961100
TI  - Intramyocardial tumors.

PMID- 10961101
TI  - Atheromas of the thoracic aorta: clinical and therapeutic update.

PMID- 10961102
TI  - [The effect of easily assimilable carbohydrates on the degree of dental enamel
      mineralization].
AB  - Clinical and experimental studies on 64 children aged 3-4 years and 80 non-inbred
      rats showed that the degree of dental enamel mineralization depends on the level
      of consumption of easily available carbohydrates during the antenatal period and
      the intensity of dental caries involvement on the degree of teeth mineralization.

PMID- 10961103
TI  - [The physicochemical aspects of ion transport across dental enamel].
AB  - Passive transport of K+, Na+ Ca2+, Cl-, and F- ions through dental enamel was
      studied with due consideration for its porous structure. Pore size was studied by
      low-temperature nitrogen adsorption. The size of pores allows penetration of
      large molecules and ions through the enamel. The internal medium of a tooth is
      connected with the electrolyte solutions surrounding it due to porous structure
      of the medium.

PMID- 10961104
TI  - [A comparative analysis of the efficacy of different types of filling materials
      in the surgical elimination of tooth perforations (experimental morphological
      research)].
AB  - Based on the experimental morphological findings, the authors compare the
      efficiency of tooth perforation repair in experimental animals by surgical method
      using Dyract compomer, Base Line glass ionomeric cement, and Ostim-100
      osteoplastic material. The data indicate a high efficiency of this method. Base
      Line material is preferable for filling the perforation in dental wall, as it
      reliably performed the isolating function under experimental conditions.

PMID- 10961106
TI  - [A method for using Stokos, a new generation of laser surgical apparatus, for
      treating diseases of the periodontium and oral mucosa in a large-volume
      outpatient setting].
AB  - Presents the design, technical characteristics (wave length 10.6 microns, power 5
      W, continuous regimen) and methods of use of a new generation laser device ALSH-5
      Plasma-R "Stokos", used for treating oral diseases (periodontal and oral mucosa
      diseases, odontogenic inflammations, reconstructive and plastic operations,
      etc.).

PMID- 10961105
TI  - [A comprehensive study of the mechanisms of the development of chronic
      inflammation in periodontitis].
AB  - Bacteriological and cytological analysis of the saliva, dental plaques, and
      gingival fluid was carried out in 48 patients with periodontitis and 25 donors.
      The concentrations of proinflammatory cytokines IL-1 and TNF-alpha were
      increased, the levels of anti-inflammatory cytokines IL-4 and TFR beta-1 were
      decreased, and MIF production was suppressed in the patients in comparison with
      donors. Important theoretical and practical recommendations are offered.

PMID- 10961107
TI  - [The antagonistic activity of the eubiotic Maxilin towards wound infection and
      its effect on the antibiotic resistance of microorganisms].
AB  - Antagonistic activity of lactic acid bacteria of strain N 2585 of "Maxilin"
      probiotic in respect to the strains S. aureus, P. aeruginosa, E. coli, Candida
      albicans and their effect on the level of sustainability of the antibiotic
      resistant strains S. aureus, E. coli, P. aeruginosa, which are extracted from the
      patients with open fractures of the mandible under various course of wound
      process, have been studied. The studies showed that lactic acid bacteria have
      suppressed growth of strains Candida most actively, followed by P. aeruginosa, S.
      aureus and E. coli. The use of "Maxilin" probiotic allowed reducing the
      epidemiological significance of pathogenetic strains already in 3 to 4 days. The
      sensibility studies showed high activity of the lactic acid bacteria in reducing
      antibiotic resistance of the strains investigated. It was revealed that "Maxilin"
      probiotic affects Ps. aeruginosa effectively, somewhat less St. aureus and E.
      coli. The extracted strains demonstrated sensibility to all investigated
      antibiotics already in 3 to 4 days.

PMID- 10961108
TI  - [The clinical characteristics of mandibular fractures in middle-aged and elderly
      subjects].
AB  - The authors analyze case histories of 642 patients aged over 50 years with
      mandibular fractures, treated in 1988-1998 at Clinic for Maxillofacial Surgery of
      Russian State Medical University. Multiple fractures occurred in patients with
      mandibular adentia 1.5 times more often than in patients with teeth. The sites of
      fractures were different in patients with intact occlusion and in those without
      teeth. Contrary to the traditional opinion, the study showed a high incidence of
      open mandibular fractures in patients both with and without teeth. Inflammatory
      complications develop more often than in other age groups, which refers this
      category of patients to high risk group and requires improvement of methods for
      their treatment.

PMID- 10961109
TI  - [The dynamics of the immune indices with the use of immunomudulin in patients
      with a mandibular fracture].
AB  - Forty-one patients with fractures of the lower jaw and 20 health donors have been
      examined. Patients with unilateral mandibular fractures received a conventional
      treatment (group 1) patients with bilateral mandibular fractures received a
      conventional treatment and immunomodulin (group 2). Results of investigations
      showed that immunity indices in patients of group 1 at admission to the hospital
      were in the normal limits, and reduced by the discharge. Immunity findings in
      patients of group 2 were rather decreased at admission, and normal after use of
      immunomodulin. Complications in group 2 were less frequent than in group 1.

PMID- 10961110
TI  - [The treatment of patients with traumatic osteomyelitis of the mandible by using
      porous permeable titanium nickelide implants].
AB  - Use of titanium nickelide based porous permeable implants for repair of
      postosteomyelitis mandibular defects is discussed. Five patients with mandibular
      defects of different location and extent were operated on. Surgical methods are
      described. A clinical example of using a porous permeable implant is offered. The
      implant designed as a mandible was used for repair of an extensive mandibular
      defect. Good immediate and remote results of operations indicate good prospects
      of using such implants.

PMID- 10961112
TI  - [A method for eliminating mandibular defects with a complex graft based on the
      sternocleidomastoid muscle].
AB  - Studies of surgical anatomy of the sternocleidomastoid muscle with the adjacent
      skin and clavicle site helped determine the variants of entry of the major
      neurovascular bundle into the muscle in surgical repair of mandibular defects
      with complex transplants on a mobile neurovascular pedicle. The location of
      "portae" does not depend on the patient's sex and is determined by age and
      constitutional type. The location of muscular port determines the pattern of the
      transplant.

PMID- 10961111
TI  - [The results of using a compression-distraction method for eliminating mandibular
      defects and deformities].
AB  - Intraoral supraosseous compression-distraction devices (CDA) have been used for
      repair of mandibular underdevelopment and defects of different etiology at
      Central Institute of Stomatology since 1997. The distraction regenerates have
      been examined by ultrasonography, roentgenography, and echo-osteometry. These
      methods allow timely correction of the course of distraction and rule out
      formation of wrong hypotrophic distraction regenerates.

PMID- 10961113
TI  - [A rare case of an aneurysmal cyst of the mandibular condyle].
AB  - A rare case with aneurysmatic cyst located near the condylar process is
      described. The treatment consisted in curettage of the formation and filling of
      the cavity in the condylar process. The operation was performed through the
      mouth.

PMID- 10961114
TI  - [Dental crowns made from a titanium alloy prepared by a superplastic molding
      method].
AB  - The possibility of making titanium tooth crowns by superplastic molding has been
      investigated. Optimal materials and technological parameters have been selected:
      Siolit molding mass, fixing composition for facing with plastic (Targit link +
      opaquer), method for tooth preparation under such crowns (step 135, stump height
      to diameter ratio 1.5:1, smooth transfer from occlusion surface to others, and
      disposition of stamps in the press form.

PMID- 10961115
TI  - [Guywire dentures].
AB  - Analyzes possible complications and shortcomings of traditional prosthetic
      treatments. Presents a new approach to prosthetic treatment and describes the
      general design of guy dentures. Describes in brief the biomechanics, methods of
      making guy dentures, and discusses their advantages in comparison with the
      traditional dentures.

PMID- 10961116
TI  - [The correlation of the occlusal plane and the Frankfurt Horizontal parameters
      with the morphological and functional indices of the maxillofacial area in
      physiological dentition relationships].
AB  - Anthropometric, functional, and teleroentgenographic examinations were carried
      out in 26 subjects aged 20-27 years with functional occlusion. Correlation of
      occlusion plane direction (OcP) with respect to the Frankfurt horizontal line
      (FH) and the dental, gnathic, and soft tissue parameters of the head and
      maxillofacial muscular functions was studied. The angle formed by the Frankfurt
      horizontal line and occlusion plate (FH-OcP) depends on the anthropometric
      angular and linear osseous parameters of the facial skull and soft tissue
      parameters of the face and with the functional status and coordination activity
      of maxillofacial muscles antagonists and synergists. It is noteworthy that the FH
      OcP angle depends on the level of disposition and, which is still more important,
      on the direction of occlusion surface, and evaluation of individual OcP is the
      key to restoration of the morphofunctional harmony of the maxillofacial system
      during orthodontic treatment.

PMID- 10961117
TI  - [The formulation of the prediction of financial results in the activities of a
      dental enterprise].

PMID- 10961119
TI  - [A method for mandibular osteosynthesis with a Kirschner wire in combination with
      applying an incomplete bone suture].

PMID- 10961118
TI  - [The reaction of the periapical tissues to Canasone released during the treatment
      of chronic pulpitis].

PMID- 10961120
TI  - [Stages in the development and organization of dentistry in Saratov Guberniya
      from 1870 to 1998].

PMID- 10961121
TI  - [The history of the use of lasers for preparing hard dental tissues].

PMID- 10961122
TI  - [The biocompatibility of alloys used in dentistry].

PMID- 10961123
TI  - [Thermometry of cadavers].
AB  - The purpose of this study was to analyze the norm-setting documents on the order
      of thermometry, regulating the steps of physician during examination at the site
      where the cadaver was found and of medical expert during expert evaluations and
      to disclose the relationship between the depth to which the thermometer is
      inserted during measurements of rectal temperature and thermometry value. The
      following conclusions are made: 1) even at the same time of death, the data of
      rectal thermometry are in direct proportion to the depth to which the thermometer
      is inserted into the rectum; 2) some assumptions in the norm-setting documents
      regulating the order of cadaver thermometry are to be revised; and 3)
      thermometers and method of thermometry performed by medical specialists at the
      site of accident and by experts at thanatological departments of Bureaus of
      Forensic Medical Expert Evaluations are to be standardized.

PMID- 10961124
TI  - [Problems in biomechanics of life-time intracranial injuries].
AB  - Discusses the impact of kinetic energy and number of head movements during
      falling from a standing posture on one's back for various variants of falling on
      the formation of subdural hematomas, subarachnoidal hemorrhages, and brain
      concussions in the areas of the stroke, contralateral to the stroke, and
      intermediate. Discloses the correlations between the area and volume of injury
      and changes in energy parameters of stroke impact. Demonstrates the relationship
      between the severity of atherosclerotic involvement of the vessels and the volume
      and type of intracranial injury.

PMID- 10961125
TI  - [Expert evaluation of damage to health in dental injuries].
AB  - Discusses problems in forensic medical expert evaluation of the severity of
      dental injuries. Analyzes the classification of dental injuries and criteria for
      their expert evaluation. Considers some disputable and contradictory problems in
      expert interpretation of dental injuries involving complete loss of teeth and
      evaluation of injuries in subjects with maxillodental diseases. Offers approaches
      to solution of these problems.

PMID- 10961126
TI  - [Biological traces after falling on the staircase].
AB  - Presents the results of experimental studies of biological traces which adhered
      during simulation of a trauma on a staircase, making use of anthropometrically
      balanced mannequins and biomodels. Analyzes blood and dust traces on clothes and
      shows that their position on clothes depends on the presence of pre-acceleration.

PMID- 10961127
TI  - [Medical anthropological aspects of hand phalanx dermatoglyphics].
AB  - Main and middle phalanx skin patterns represent a polymorphic hereditary system
      of signs practically not studied in anthropology, but interesting for forensic
      medicine and criminology from the viewpoint of expert evaluation of relation and
      personality identification. Based on a vast scope of data (600 hand impressions
      of 300 subjects from Russian families), a classification of patterns on the main
      and middle finger phalanges has been developed and their incidence evaluated. The
      proposed classification includes 15 types and 40 subtypes. The incidence of
      individual patterns on phalanges of different site and order has been determined.
      The problem of genetic determination, i.e. inheritance of certain patterns from
      father and mother, remains open and requires a special research.

PMID- 10961129
TI  - [Some aspects in preparation and use of wide spectrum antiglobulin sera in
      forensic medical studies].
AB  - Wide spectrum (polyspecific) antiglobulin sera were obtained by rabbit
      immunization with 10% solution of zymosan-charged globulin (product of yeast
      digestion with trypsin) with complete Freund's adjuvant. The resultant sera meet
      the international standards and can be used for forensic medical identification
      of serum G1m(1) group and for detecting incomplete antierythrocytic complement
      fixing anti-Daffi, anti-Kell, and other antibodies in blood transfusion service.

PMID- 10961128
TI  - [Forensic medical significance of anti-P1 immunoreagents with incomplete
      antibodies in blood analysis].
AB  - Anti-P1 immunoreagents with incomplete antibodies are intended for detection of
      antigen of different degree of manifestation in blood traces during expert
      evaluation of material evidences by the adsorption-elution test. These reagents
      can be used for detecting weakly manifest P1 antigen in liquid blood in forensic
      medical studies.

PMID- 10961130
TI  - [Preparation, evaluation of specificity and use of anti-Le monoclonal
      antibodies].
AB  - Anti-Le(a) and anti-Le(b) monoclonal antibodies were obtained and attempts at
      evaluating their epitope specificity have been made. A method for identification
      of Lewis phenotypes in salivary specimens by dot-I enzyme immunoassay has been
      developed. Analyses of salivary samples from 72 donors detected donors with
      phenotypes Le(a-b-) and Le(a+b+), which was confirmed by hemagglutination test.

PMID- 10961131
TI  - [Detection of semen in stains on material evidences by quantitative
      immunofluorescence test].
AB  - Russian and foreign methods used in forensic medicine for detection of the semen
      in stains on material evidences are compared. The potentialities of quantitative
      immunofluorescence test for detection of the semen in stains on material
      evidences, developed at Bureau for Forensic Medical Expert Evaluations of the
      Leningrad region, are described. Unlike other methods used in Russia, this method
      detects the semen in stains in the absence of spermatozoa and in stains with very
      low amount of the semen. Our modification allows objective recording of the
      results with computer processing. The method is cheaper than its foreign analogs
      and its sensitivity is similar to them.

PMID- 10961132
TI  - [Study of cuticle patterns of head hairs by scanning electron microscopy].
AB  - Cuticle patterns of 5 subjects living in different countries have been studied
      under a scanning electron microscope. Hair cuticle pattern in different
      individuals can be complex, simple, or mixed type. The most incident is the
      complex type of hair cuticle pattern (75-80%), while the simple type is much more
      rare (15-20%) and the mixed type still more rare (2-5%). Variation statistical
      analysis helped differentiate hairs from aborigines of some countries of Asia,
      Africa, Latin America, and East Europe by the number of cuticle pattern lines.
      High efficiency of scanning electron microscopy in studies of hair cuticle
      patterns is shown.

PMID- 10961133
TI  - [Use of amelogenin test for DNA sex appurtenance in analysis of mixed biological
      traces].
AB  - Theoretical and experimental study of amelogenin tests system for identification
      of DNA sex appurtenance has been performed. In many cases amplification can fail
      to reflect the true quantitative ratio between the mixture components during
      typing sex-specific variants of amelogenin gene in DNA preparations of mixed sex
      appurtenance. In practical studies these properties of the amelogenin system can
      lead to difficulties and errors in interpretation of the results of forensic
      medical expert evaluations, and we therefore studied the use of amelogenin DNA
      test for identification of sex appurtenance of mixed biological traces and
      compared the characteristics of autosomal PDAF system and amelogenin system for
      sex identification in analysis of DNA mixtures.

PMID- 10961134
TI  - [New structural subdivision: United Narcological Toxicological Center attached to
      Saratov Regional Bureau for Forensic Medical Expert Evaluations].

PMID- 10961135
TI  - [Diagnosis of lethal benzene inhalation intoxications].

PMID- 10961136
TI  - [Sudden death from exacerbation of interstitial myocarditis combined with trauma
      and chronic alcoholism].

PMID- 10961137
TI  - [Use of borate and veronal buffers for identification of blood species
      appurtenance by counter-current immunoelectrophoresis in agar gel].

PMID- 10961138
TI  - [N.Kh. Ketcher - Moscow forensic specialist and writer].

PMID- 10961139
TI  - [Effects of sodium nitrite, a NO donor, on activity of neurons in visual and
      sensorimotor regions of cortex during learning].
AB  - Administration of sodium nitrite, NO-generating agent, in a dose of 11 mg/kg to
      conscious rabbits eliminates the increased rates of movements to pain
      reinforcement which occurs as combinations of light flashes with electric
      cutaneous irritation recur in the control. Along with this, there is a reduction
      in the intensity and duration of short latent "modally specific" components in
      the neuronal responses of visual (to light flashes) and sensomotor (to pain
      reinforcement) regions of a new cortex. There were less changes in the late
      latent activation components of neuronal responses of the sensomotor and visual
      cortex to pain reinforcement, an inhibitory pause in visual neuronal responses to
      light flashes, its uninhibitory action of pain reinforcement after sodium nitrite
      administration. The findings suggest that sodium nitrite exerts a neurotropic
      effect on its systemic administration and support the views that there are
      differences in the neuromediatory provision of transmission of "modally specific"
      and "modally nonspecific" effects to the neurons of the new cortex on radiation.

PMID- 10961140
TI  - [Activity of gastric mucosal NO synthase in duodenal ulcer].
AB  - The paper covers the results of 32 endoscopic studies. The D. E. Korzhevsky
      procedure was used to determine the activity of NADP.H diaphorase, a NO-synthase
      marker, in gastric mucosal biopsy specimens from patients with acute and scarring
      peptic ulcer. A high activity of NO synthase was found in patients with acute
      ulcer and its inhibition was ascertained in those with scarring ulcer. The
      findings lead to the conclusion that NO-dependent mechanisms are involved in the
      pathogenesis of an ulcerative process.

PMID- 10961141
TI  - [Modifying effect of nitrites on pulmonary blastogenesis and viral leukogenesis
      in mice: role of nitric oxide and dioxide].
AB  - The long-term effects of sodium nitrite (NaNO2) on carcinogenesis induced by
      urethane (total dose 1.0 mg/g body weight) in low-grade cancer F1 (C57BLxCBA) and
      high-grade A/Snell mice and on viral (Rausher leukemia virus) leukomogenesis in
      Balb/c mice. The murine intake of NaNO2 with water (50 mg/l) causes a
      statistically significant increase in the number of adenomas in the lung.
      Examining the mechanism of conversion of NO2- to NO led to the assumption that
      the free radical compounds NO and NO2 are involved in the potentiating action of
      NO2 on blastomogenesis. The use of the oxidant emoxypine (3-hydroxypyridine)
      confirmed the above. The role of NO and NO2 in the intracellular processes under
      the modifying effects of nitrites and nitrates on blastomogenesis is analyzed.

PMID- 10961142
TI  - [Clinical manifestations and diagnosis of rhabdomyosarcoma of childhood at
      different sites].
AB  - Soft tissue sarcomas occupy the fourth place in the pattern of malignant
      neoplasms in children. Rhabdomyosarcoma (RMS) is more common (about 38%) among
      various morphological variants of soft tissue sarcomas. The specific features of
      RMS sites (the head and neck, torso and extremities, viscera, small pelvis,
      chest, and abdomen, genitalia) determine a diversity of clinical manifestations,
      as well as diagnostic problems. There are a great deal of diagnostic errors that
      are as high as 85%. Diagnosing RMS in children should be comprehensive and based
      on clinical, instrumental, laboratory, X-ray, radionuclide, ultrasonic, and
      morphological findings.

PMID- 10961143
TI  - [ES-IPO-97 treatment protocol for prognostically poor Ewing's sarcoma forms in
      children: results of implementation].
AB  - The paper shows the high efficiency and moderate toxicity of inductive treatment
      in children with Young sarcoma and primitive neuroectodermal tumors by ES-Ipo-97
      protocol that includes alternate chemotherapy by the scheme: vincristine, 1.5
      mg/m2/day, on days 1, 8, 15; adriamycin, 37.5 mg/m2/day, on days 1 and 2 as 24
      hour infusion; cyclophosphanum, 2.1 g/m2/day, on days 1 and 2 (Block A);
      iphosphamide, 2.4 g/m2/day on days 1 to 5, etoposide, 100 mg/m2/day, on days 1-5
      (Block B). It provides evidence for that this therapy is promising and awaits
      further developments.

PMID- 10961145
TI  - [Genomic investigations in genetic cardiology: status and prospects].
AB  - The paper discusses relations of new disciplines in medical science, such as
      genetic cardiology and genomic medicine. It outlines today's achievements and
      prospects of genomic studies for some groups of cardiovascular diseases:
      congenital developmental defects of the heart and great vessels, cardiac
      arrhythmias and cardiomyopathies, and common diseases with complex inheritance,
      such as atherosclerosis and arterial hypertension. Accumulated knowledge on new
      candidate genes of these forms of pathology specifies their pathogenesis, makes
      it possible to outline new gene-specific therapeutical approaches, and serves as
      a basis for classifying risk groups by specific diseases. On the other hand,
      studies of the "sphere of influence" (fields of action) of genes that make up a
      molecular genetic basis of diseases are of fundamental value in defining the
      physiological role of sequenced human genomic fragments (functional genomics).

PMID- 10961144
TI  - [Analysis of DNA excreted from the body as an approach to diagnosis and
      monitoring tumor growth].
AB  - Proceeding from their early data showing that some portion of DNA originating
      from apoptotic cells can enter the blood stream and pass through the renal
      barrier by preserving its template capabilities, the authors analyzed urine DNA
      from 29 patients with colorectal cancer. PCR was used to compare DNA samples from
      the normal mucosa surrounding the tumor and from the urine collected just prior
      to surgery. Six microsatellite loci were studied with oligonucleotide primers.
      The following results were obtained: i) 3 cases showed differences in one of the
      studied loci in normal and tissue DNA; ii) some patients displayed changes in
      urine DNA microsatellite loci, namely: disappearance of some alleles (loss of
      heterozygocity) and appearance of new ones; iii) there were no differences in
      microsatellite patterns of lymphocytic DNA (taken as a control) and urine DNA in
      healthy donors. The findings are discussed in view of current concepts of tumor
      clonal heterogeneity and interpreted as a promising approach to diagnosing and
      monitoring tumor growth.

PMID- 10961146
TI  - [Construction by using retrovirus vector of recombinant with synthetic bradykinin
      "gene" for investigations of human gene expression in mammalian cells].
AB  - The synthetic gene of bradykinin was built into the retrovirus vector pPS-3-neo
      under the guidance of LTR promotor, followed by pPS-3-neo (brd) vector
      transfection of strain 293 cells. The physiological activity of the expressed
      bradykinin was tested on cultured neonatal rat cardiomyocytes. The culture medium
      of strain 293 cells transferred by pPS-3-neo (brd) produces a positive
      chronotropic effect that is directly related to the time parameters of
      preparation of recombinant bradykinin, which are comparable with the curve of
      chronotropic effect of synthetic bradykinin at concentrations of 10(-17) to 10(
      16) M. The control of bradykinin "gene" expression was due to the lack of
      chronotropic responses of cardiomyocytes to the kinin receptor blocker parmidine
      and the transfection of strain 293 cells with the retrovirus vector without
      bradykinin "gene".

PMID- 10961147
TI  - [Holmium laser in chondrology: potentials and prospects].
AB  - To study the mechanism of simulation of a cartilage, to define the optimum
      parameters and laser radiation regimens, the authors made a complex of in vitro
      experiments on the cartilages of the nasal septum in man and domestic animals and
      in vivo experiments on those of the concha in rabbits and pigs. Holmium laser
      radiation is shown to be the most suitable tool for formation of a cartilage.
      Evidence is provided for the possibility of irreversibly altering the shape of a
      cartilage during laser radiation. A procedure has been developed for non-invasive
      correction of the septum of the nose for its curvature. Restored or improved
      nasal respiration was observed in more than two thirds of the patients. Laser
      surgery is not of age-limited application, it is noninvasive, can be performed in
      the outpatient settings and requires no drug treatment in the postoperative
      treatment.

PMID- 10961148
TI  - [Applied aspects of allometry use in human ecology].
AB  - The paper shows it possible to use allometric equations to detect human and
      animal biological differences, including longevity. An actual man is shown to
      generally live 5 times longer than his allometric model constructed on the mean
      life longevity in mammals of different species from shrewmouse to elephant. The
      longer life of man is accounted for by his biosocial nature and by the influence
      of many socioeconomic factors. Therefore the mean longevity may serve as a
      universal integral index of the socioeconomic policy of some countries and
      regions. Critical considerations should be hold for the attempts to substitute
      the socioeconomic situation by the pure ecological one when outlining prospects
      of society development. Environmental protection programmes should not become an
      end in themselves, but they should be only a constituent of the general concept
      of development wherein priority is given to the socioeconomic problems of the
      population's life.

PMID- 10961149
TI  - [Problems in public health care in the programs of political parties and social
      movements of today's Russia].

PMID- 10961150
TI  - [Mitochondrial diseases].

PMID- 10961152
TI  - Author and subject indexes (1998) 211-223.

PMID- 10961151
TI  - [From the history of establishment of medical genetics in Russia].

PMID- 10961153
TI  - Licence to publish--authors in the British Journal of Nutrition now retain the
      copyright of their material.

PMID- 10961154
TI  - The effects of iron and copper status and of dietary carbohydrates on the
      activity of rat intestinal beta-carotene 15,15'-dioxygenase.

PMID- 10961155
TI  - Nutritional factors in stroke.
AB  - Observational studies support the role of modifying lifestyle-related risk
      factors such as diet, physical activity and alcohol use in stroke prevention. For
      example, increased Na intake is associated with hypertension, and reduction in
      salt consumption may significantly lower blood pressure and may reduce stroke
      mortality. Moderately elevated homocysteine levels may be associated with stroke
      and are associated with deficiency of dietary intake of folate, vitamin B6 and
      vitamin B12. Consumption of a diet rich in fruits, vegetables, folate, K, Ca, Mg,
      dietary fibre, fish and milk may protect against stroke. Regular physical
      activity may also protect against stroke through its role in controlling various
      risk factors such as hypertension, diabetes mellitus and obesity. The role of fat
      intake as a risk factor for stroke remains uncertain, whereas the association
      between stroke and cholesterol has more convincingly been demonstrated by the
      recent intervention trials using statins. There is also evidence that a low serum
      albumin may be causally linked to stroke risk and outcome and that a significant
      number of stroke patients are undernourished on admission and their nutritional
      status deteriorates further whilst in hospital. Undernutrition is associated with
      increasing morbidity and mortality and nutritional supplements may have some
      beneficial effect on some outcome measures.

PMID- 10961156
TI  - Evaluation of role of concentration and molecular weight of oat beta-glucan in
      determining effect of viscosity on plasma glucose and insulin following an oral
      glucose load.
AB  - Data from clinical studies established that there was an inverse linear
      relationship between measures of postprandial blood glucose and insulin responses
      to an oral glucose load, consumed in a drink, and the logarithm of viscosity of
      the drink. These data have been re-analysed using concentration and molecular
      weight as the dependent variables. Molecular weight (M) of the beta-glucans used
      was determined using high-performance size exclusion chromatography equipped with
      a triple detector system of right angle light scattering, viscometry and
      refractive index. A significant relationship between changes in peak blood
      glucose and a combination of logarithm of the concentration and logarithm of M
      was found.

PMID- 10961157
TI  - Changes in macrophage and lymphocyte functions in guinea-pigs after different
      amounts of vitamin E ingestion.
AB  - Vitamin E is the main biological lipid-soluble antioxidant and plays a crucial
      role in the maintenance of the immune system. In the present work, twenty-one
      guinea-pigs (3-weeks-old) were distributed into three groups, which during 5
      weeks ingested different amounts of vitamin E (/kg diet): 15 mg (low vitamin E
      diet), 150 mg (medium vitamin E diet; control) or 1500 mg (high vitamin E diet).
      The function of lymphocytes and macrophages were then studied. In macrophages
      obtained from the peritoneum several steps of the phagocytic process (chemotaxis,
      ingestion and superoxide anion production) were assayed, as well as chemotaxis
      and proliferation of peritoneal and spleen lymphocytes. The results indicate that
      with respect to the medium vitamin E diet, low ingestion of vitamin E causes a
      decrease in chemotaxis and production of superoxide anion by macrophages and an
      increase in the phagocytic capacity. With the high vitamin E diet an increase in
      macrophage and lymphocyte chemotaxis, superoxide anion production and
      lymphoproliferative capacity, as well as a decrease in phagocytosis, were
      observed. Therefore, diet supplementation with higher than usual levels of
      vitamin E appears to be beneficial for the immune system.

PMID- 10961158
TI  - Short-chain fatty acids produced in vitro from fibre residues obtained from mixed
      diets containing different breads and in human faeces during the ingestion of the
      diets.
AB  - It was studied whether the type of bread (i.e. a low-fibre wheat-rye mixed bread
      and coarse or fine wholemeal rye bread) either as part of a diet or alone, had an
      influence on the short-chain fatty acids (SCFA) produced during in vitro
      fermentation. Fermentation substrates were dietary fibre residues obtained from
      diets and breads. In addition, it was investigated whether the faecal SCFA
      pattern in the inoculum donors, who ingested the experimental diets, could be
      predicted by in vitro fermentation. Yields of SCFA in vitro were 0.51-0.62 g/g
      fermented polysaccharide. In vitro, the molar ratios of butyrate were higher for
      the two high-fibre diets containing coarse or fine wholemeal bread than for the
      low fibre diet containing wheat-rye mixed bread; the difference was significant
      for the coarse (P < 0.01), but not for the fine bread diet (P = 0.0678). The
      coarse wholemeal bread alone produced a higher molar ratio of butyrate than the
      fine wholemeal bread (P < 0.05) and the wheat-rye mixed bread (P < 0.01).
      Ingestion by the inoculum donors of the diets containing wholemeal bread led to
      higher faecal butyrate ratios (molar ratios: coarse bread diet 19.6, fine bread
      diet 17.7) compared with the wheat-rye mixed bread-containing diet (14.9), but
      the differences between the diets were not significant. For the diets
      investigated, there were no significant differences between faecal and in vitro
      SCFA patterns.

PMID- 10961159
TI  - Food viscosity as determinant for adaptive growth responses in rat intestine:
      long-term feeding of different hydroxyethyl celluloses.
AB  - Carbohydrate gelling agents can be regarded as being representative for the
      soluble and viscous fractions of dietary fibre. Their dietary concentration
      affects the consistency of the ingested food as well as the dilution of nutrients
      and energy. By feeding hydroxyethyl cellulose (HEC) differing in molecular mass,
      and thus in its viscosity properties, only the consistency of the diet was
      modified. Three HEC (of low (LV), medium (MV) and high viscosity (HV)) were
      employed in a 6-week feeding study with female rats to evaluate the effect of the
      viscosity on adaptive responses of intestinal growth variables. Each of the HEC
      was added in three increasing concentrations (8, 16, and 32%, w/w) to a fibre
      free control diet to yield nine test groups besides a fibre-free and an
      additional, fibre-rich, cereal-based control group. Except for the highest
      concentration of the high viscosity product (32% HV-HEC), the dilution of the
      energy density of the diet was almost completely compensated by an increased food
      intake. With the same exception, energy utilisation was not impaired and,
      therefore, body-weight gains in the test groups were not significantly different
      from that in the control. Most other changes, e.g. increases in small intestinal
      length, mucosal DNA content, caecal and colonic weight, not only depended on the
      dietary concentration but also on the viscosity of HEC in a manner that either
      increasing the viscosity at a given dietary concentration or increasing the
      dietary concentration at a given viscosity led to the same results. These
      findings clearly prove the important role of the viscosity of the lumen content,
      as a mere physico-chemical factor, in determining adaptative growth responses in
      the intestinal tract of rats.

PMID- 10961160
TI  - The effect of high salt and high protein intake on calcium metabolism, bone
      composition and bone resorption in the rat.
AB  - The effects of salt (NaCl) supplementation of rat diets (50 g/kg diet), with
      normal (200 g/kg) or high (500 g/kg) dietary casein content, were studied in 3
      week-old male rats over a 3-week period. Weight gain was reduced by dietary salt
      but was unaffected by dietary casein. Salt-supplemented rats exhibited a two- and
      three-fold increase in urinary Mg and Ca excretion respectively, irrespective of
      dietary casein content. Dietary casein had no effect on urinary Ca or Mg. Salt
      reduced femoral mass but not femoral mass expressed relative to body weight, but
      neither variable was affected by dietary casein. Femoral Mg and P contents and
      concentrations were unaffected by dietary salt or casein. While femoral Ca
      concentration was unaffected by dietary salt, the Ca content was reduced by salt
      supplementation, irrespective of dietary casein content. Neither the content nor
      concentration of Ca in femora was affected by dietary casein. Urinary
      pyridinoline and deoxypyridinoline levels were increased by salt supplementation,
      irrespective of dietary casein content, but were unaffected by casein. Net Ca
      absorption was unaffected by dietary salt or casein. In conclusion, these results
      show that salt supplementation over the short-term increased the rate of bone
      resorption in rats. This was as a consequence of Na-induced calciuria. On the
      other hand, a high dietary protein intake had no effect on Ca metabolism, bone
      composition or bone resorption, nor did it augment the Na-induced calciuria or
      increased rate of bone resorption.

PMID- 10961161
TI  - Acarbose raises serum butyrate in human subjects with impaired glucose tolerance.
AB  - The fermentation of starch in vitro produces a higher proportion of butyrate than
      the fermentation of most other substrates. The alpha-glucosidase inhibitor
      acarbose increases the amount of starch entering the colon, and has been shown to
      increase faecal butyrate in humans. It is generally considered that colonic
      butyrate is quantitatively removed by the colonic mucosa and liver and does not
      appear in peripheral blood. However, studies in animals suggest that a small
      proportion of colonic butyrate reaches peripheral blood. Thus, we hypothesised
      that an increase in colonic butyrate production would result in a rise in serum
      butyrate in human subjects. To test this, subjects with impaired glucose
      tolerance were randomly treated in a double-blind fashion with placebo (n 11) or
      acarbose (n 11) (100 mg three times per day). Serum short-chain fatty acid
      concentrations were measured twelve times over 12 h with subjects eating a
      standard diet before randomization and after 4 months of therapy. At baseline, 12
      h mean serum butyrate concentrations were similar in the placebo and acarbose
      groups (2.8 (SE 0.7) and 3.3 (SE 0.6) microM, respectively). After 4 months on
      placebo, mean serum butyrate (2.6 (SE 0.5) microM) was no different from
      baseline. However, after 4 months on acarbose, serum butyrate had increased to
      4.2 (SE 1.0) microM, a value which differed significantly from both the baseline
      value in the acarbose group and the treatment value in the placebo group. We
      conclude that acarbose increased serum butyrate in subjects with impaired glucose
      tolerance. These results support the hypothesis that increased colonic butyrate
      production in human subjects can be detected by an increase in serum butyrate.

PMID- 10961162
TI  - Changes to the quantity and processing of starchy foods in a western diet can
      increase polysaccharides escaping digestion and improve in vitro fermentation
      variables.
AB  - This study investigated how readily achievable changes to the quantity and
      processing of starchy foods in a typical Western diet: (1) were reflected in
      levels of resistant starch (RS) and NSP excreted from the small intestine; and
      (2) more favourable profiles of butyrate, NH3 and phenol production. Two diets, a
      low-starch diet (LSD) and a high-starch, low-fat diet (HSLFD) were compared. The
      LSD with 20% total energy (%E) from starch was based on a 'typical' Australian
      diet, while the HSLFD (40%E as starch) was the same Australian diet modified by
      an increased content of legumes, starchy foods and coarsely-ground cereals and by
      a reduced fat content. Four subjects with iliostomies consumed each diet for 2 d,
      with ileal effluent collection on the second day. On the HSLFD compared with the
      LSD, RS in ileal effluent increased from from 0.49 to 1.7 g/MJ per d (P < 0.005)
      while ileal NSP excretion increased from 2.0 to 3.3 g/MJ per d (P < 0.05). Ileal
      effluents obtained after each diet were incubated for 24 h in vitro with a human
      faecal innoculum. After fermentation, ileal effluent from the HSLFD produced more
      butyrate relative to other short-chain fatty acids (17.5 v. 15.8 molar %, P <
      0.005) and less phenol (2.3 v. 5.7 mg/l, P < 0.05) and NH3 (20.3 v. 23.1 mmol/l,
      P < 0.005) than the LSD diet. The HSLFD also generated a lower pH (6.15 v. 6.27,
      P < 0.05). On a wt/wt basis, RS was 2.3-fold higher in the HSLFD effluent while
      NSP did not increase, suggesting that the change in RS largely contributed to the
      fermentation effects. Changes in in vitro variables when the HSLFD ileal effluent
      was ground before fermentation indicated the importance of physical structure in
      determining ileal excretion of RS. We conclude that: (1) readily achievable
      modifications to the amount and processing of starchy foods in an Australian diet
      would produce potential benefits for in vitro fermentation variables; and (2) the
      physical structure of grains and cereals is important in determining access by
      colonic bacteria to a carbohydrate substrate.

PMID- 10961163
TI  - Effect of polyethylene glycol on in vitro degradability of nitrogen and microbial
      protein synthesis from tannin-rich browse and herbaceous legumes.
AB  - Determination of microbial degradability of N is important in formulating a sound
      supplementation strategy for efficient utilisation of basal as well as
      supplementary diet components. In vitro degradability of N (IVDN) from tannin
      containing browses (Acacia cyanophylla, Acacia albida, Acioa barteri and Quercus
      ilex) and two herbaceous legumes (Desmodium intortum and Desmodium uncinatum) was
      determined using the in vitro gas-production method coupled with NH3-N
      measurement in the presence and absence of a tannin-binding agent (polyethylene
      glycol (PEG), molecular mass 6000). Addition of PEG to tannin-containing feeds
      significantly (P < 0.05) increased in vitro gas and short-chain fatty acid (SCFA)
      production, and IVDN. The use of PEG as a tannin-binding agent increased IVDN
      from 28 to 59, 32 to 72, 19 to 40, 32 to 73, 40 to 80, and 26 to 77% in A.
      cyanophylla, A. albida, A. barteri, D. intortum, D. uncinatum and Q. ilex
      respectively. There was significant correlation between total phenolic compounds
      (total phenol, TP; total tannin, TT) in leguminous forages and percentage
      increase in IVDN on addition of PEG (P < 0.05; R2 0.70 and 0.82 for TP and TT
      respectively). The difference in IVDN observed in the absence and presence of PEG
      indicates the amount of protein protected from degradation in the rumen by
      tannins. When measured after 24 h incubation, tannin-containing feeds incubated
      in absence of PEG resulted in higher microbial protein synthesis than in the
      presence of PEG. Addition of PEG significantly (P < 0.05) reduced the efficiency
      of microbial protein synthesis expressed as mumol purine/mmol SCFA.

PMID- 10961164
TI  - The effect of dietary fibre on energy utilisation and partitioning of heat
      production over pregnancy in sows.
AB  - A low (L) and high-fibre (H) diet were fed to six multiparous sows during
      gestation in a 2 x 2 repeated Latin square design. A single meal per day was
      given that provided 37.2 MJ digestible energy/d. The kinetics of heat production
      (HP) and its partitioning (fasting HP, activity HP, and thermic effect of feeding
      (TEF)) were determined. The TEF was partitioned between a dynamic component
      (TEFst) and a constant component (TEFlt). Digestibility of energy and nutrients
      was lower for the diet H. In spite of the lower metabolisable energy (ME) intake
      (33.9 v. 35.4 MJ/d for diets H and L respectively), HP was higher for diet H
      (30.5 v. 28.9 MJ/d) resulting in a lower energy retention. The estimated fasting
      HP was 270 kJ/kg body weight 0.75 per d at day 0 of gestation and increased with
      advancement of pregnancy. The TEFlt was not significantly different from zero for
      diet L, but represented 4.1% of ME intake for diet H. The TEFst was not affected
      by the diet but diet H delayed the postprandial peak of HP. Total TEF was higher
      for diet H than for diet L (11.7 v. 8.2% of ME intake). The longer duration of
      eating with diet H was compensated for by less physical activity between meals,
      so that activity HP was equivalent for both diets. The activity HP represented
      20% of ME intake but was variable between sows. The ME requirements for
      maintenance averaged 440 kJ/kg body weight 0.75 per d. Feeding high-fibre diets
      increases HP, delays the postprandial peak of HP and maintains the basal HP at a
      higher level.

PMID- 10961165
TI  - A longitudinal study of maternal anthropometric changes in normal weight,
      overweight and obese women during pregnancy and postpartum.
AB  - Many women associate one or more of their pregnancies with the development of
      adult obesity. Such an association has not been fully explored. This longitudinal
      study examines the changes in maternal anthropometric indices during pregnancy
      and postpartum. Seventy-seven pregnant subjects were investigated longitudinally
      at about 13, 25 and 36 weeks gestation, of whom forty-seven continued taking part
      into the postpartum period. Maternal weight, height and skinfold thickness
      (triceps, biceps, subscapular, suprailiac and mid thigh) were measured at each
      visit. Maternal fat mass was estimated from the conversion of the first four
      skinfold thicknesses. Maternal waist and hip circumferences were also measured at
      the first visit and 6 weeks and 6 months postpartum. Weight and fat gain during
      pregnancy (13-36 weeks gestation) was 10.9 (SD 4.7) kg and 4.6 (SD 3.3) kg (P <
      0.001) respectively. A significant increase in fat mass from 13 weeks gestation
      to 6-months postpartum was observed (2.6 (SD 4.5), P < 0.001). The increased
      weight at 6-months postpartum, however, was not statistically significant (1.1
      (SD 6.0) kg, P = 0.20). Based on BMI in early pregnancy, the subjects were
      divided into groups of underweight, normal weight, overweight and obese. The last
      three groups were compared using ANOVA. The obese group showed a significant
      difference in the pattern of changes in the skinfold thickness, waist:hip ratio
      and fat mass at the postpartum period, in comparison with the other two groups.
      In conclusion, there is a tendency in the obese group to develop central obesity
      at the postpartum period.

PMID- 10961166
TI  - Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout
      12-months of lactation and provide a sustained intake to the infant during
      exclusive breastfeeding: an Italian study.
AB  - While a wealth of data on the fatty acid composition of mature human milk has
      been published, limited information is available on the quantities of individual
      fatty acids supplied to the suckling infant with maternal milk, through the whole
      first year of life. Our aim was to qualitatively and quantitatively evaluate the
      fatty acid composition of human milk from Italian mothers, throughout extended
      lactation with particular emphasis on the long-chain polyunsaturated fatty acids.
      We have thus measured the total fat content and the concentrations of major fatty
      acids by quantitative GLC in pooled breast hindmilk collected from all feedings
      over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after
      delivery of full-term infants. Total saturated fatty acids progressively increase
      and total monounsaturated progressively decrease as percentage levels, while
      among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and
      docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk
      total lipids (mg/dl) rise more than twofold up to 3 months, and then remain
      stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid
      progressively increase, following the trend of total fat, while arachidonic and
      docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing
      period. Assessment of the intakes per kg body weight shows different trends for
      the individual major long-chain polyunsaturated fatty acids supplied to the
      infant from hindmilk during exclusive breast-feeding (3 months). This information
      may be useful for the evaluation of infant intakes during extended lactation.

PMID- 10961167
TI  - Parathyroid hormone is elevated but bone markers and density are normal in young
      female subjects who consume inadequate dietary calcium.
AB  - Dietary Ca and osteocalcin (OC), parathyroid hormone (PTH), 25-hydroxyvitamin D
      (25-OH-D), insulin-like growth factor (IGF)-I and sex hormone binding globulin
      (SHBG) were assessed simultaneously to bone mineral density (BMD) in 200
      adolescent girls (aged 11-15 years) and 100 young women (aged 20-23 years),
      selected from the lowest and highest end of the Ca intake distribution of a
      larger population sample. Ca intake was evaluated by food frequency
      questionnaires, BMD was measured by dual energy x-ray absorptiometry at
      ultradistal and proximal radius of non-dominant arm, bone age was estimated from
      x-rays of left hand and wrist according to Tanner et al. (1983). Surprisingly,
      mean Ca intakes were below the dietary reference intakes in the subgroups of
      girls and women with the highest measured Ca consumption. Postmenarcheal, but not
      premenarcheal girls showed radial densities as high as the women and in no group
      was BMD associated with Ca intake. In all adolescents serum PTH was negatively
      related to dietary Ca. In girls before menarche IGF-I was positively associated
      with bone age, while in the same subjects the negative relationship between SHBG
      and BMD pointed to the crucial role of bioavailable sex steroids on bone mass
      apposition in early puberty. OC levels decreased progressively with age, while
      serum 25-OH-D significantly increased after menarche. In conclusion, although in
      adolescents low Ca intake has not been shown to induce any immediate deleterious
      effect on radial density, the compensatory hypersecretion of PTH supports the
      need for an adequate Ca intake to achieve peak bone mass.

PMID- 10961168
TI  - Intestinal beta-carotene 15,15'-dioxygenase activity is markedly enhanced in
      copper-deficient rats fed on high-iron diets and fructose.
AB  - The purpose of the present work was to examine effects of the Cu-Fe interaction
      on intestinal beta-carotene 15,15'-dioxygenase activity when a wide range of
      dietary Fe (deficiency to excess) was used in relation to Cu status of rats. The
      effect of dietary carbohydrates was also examined since they play a role in the
      Cu-Fe interaction in vivo. Weanling male Sprague-Dawley rats (n 72) were divided
      into twelve dietary groups, which were fed on either low-, normal-, or high-Fe
      levels (0.9, 9.0, and 90.0 mmol Fe/kg diet respectively) combined with Cu
      adequate or -deficient levels (0.94 and 0.09 mmol Cu/kg diet respectively) and
      with starch or fructose in the diets. The data showed that both Fe concentration
      and beta-carotene 15,15'-dioxygenase activity in small intestinal mucosa were
      enhanced with increasing dietary Fe and with Cu deficiency v. Cu adequacy.
      Dietary fructose did not aggravate the Fe-enhancement, related to Cu deficiency,
      in the small intestine; however, fructose increased the intestinal dioxygenase
      activity in rats fed on normal- or high-Fe diets when compared with starch
      controls. Thus, the highest intestinal dioxygenase activity associated with the
      lowest hepatic retinol (total) concentration was found in rats fed on the Cu
      deficient, high-Fe, fructose-based diet. Finally, a positive linear relationship
      was found between the dioxygenase activity and Fe concentration in intestinal
      mucosa. In conclusion, the data indicate that beta-carotene 15,15'-dioxygenase
      activity requires Fe as cofactor in vivo and the enzyme is modulated by the three
      dietary components: Cu, Fe, and fructose.

PMID- 10961169
TI  - Moderate maternal vitamin A deficiency affects perinatal organ growth and
      development in rats.
AB  - Vitamin A deficiency during pregnancy is associated with detrimental effects in
      the offspring. We have developed a rat model to examine specific effects of
      maternal vitamin A status on perinatal growth and development. A total of 54
      female rats were fed a vitamin A-free (VAF), -marginal (VAM) or -sufficient (VAS)
      diet from weaning until mating (at 7 weeks) and throughout pregnancy. Half of the
      rats in each group were injected with a single large dose of vitamin A on day 10
      of pregnancy. Fetal and neonatal samples were taken on day 20 of pregnancy and
      the day of birth respectively. Maternal plasma retinol concentrations on day 20
      and at birth were 50% and 30% lower in the VAF and VAM when compared to the VAS
      group. Fetal weight and survival did not differ between groups although
      placental:fetal ratio was higher in the VAF group than in the VAS group (0.195
      (SE 0.005) v. 0.175 (SE 0.004), P < 0.05). Rats fed the VAF diet gave birth at
      23.5 d, an average of 1 d later than the other groups, and had lower number of
      live neonates at birth. Fetal liver, heart and lung weights relative to total
      body weight were lower in the VAF group and had altered growth trajectories. In
      neonates, only the relative lung weight was reduced. In addition, an increased
      protein:DNA ratio indicated hypertrophy in fetal kidneys. Vitamin A injection had
      no additional effect on length of gestation and fetal or neonatal number.
      However, injection increased relative fetal organ weights in the VAF group but
      did not alter the effects of vitamin A deficiency in the neonate. These data
      suggest that chronic vitamin A deficiency during pregnancy compromises liver,
      heart and kidney and impairs lung growth and development during the last few days
      of gestation and reduces number of live neonates at birth.

PMID- 10961171
TI  - Current understanding of the pathophysiology of thrombotic thrombocytopenic
      purpura.

PMID- 10961172
TI  - Molecular techniques for clinical diagnostic virology.

PMID- 10961173
TI  - acp. Best practice no 161. Examination of lung specimens.
AB  - This article gives guidance for the handling and examination of various types of
      lung tissue specimens to provide: (1) accurate diagnosis and assessment of
      severity of disease; (2) sufficient information for the accurate staging of
      tumours; and (3) an assessment of the contribution of various occupational
      disorders to the cause of death.

PMID- 10961170
TI  - Lipoprotein (a) and stroke.
AB  - Strokes are one of the most common causes of mortality and long term severe
      disability. There is evidence that lipoprotein (a) (Lp(a)) is a predictor of many
      forms of vascular disease, including premature coronary artery disease. Several
      studies have also evaluated the association between Lp(a) and ischaemic
      (thrombotic) stroke. Several cross sectional (and a few prospective) studies
      provide contradictory findings regarding Lp(a) as a predictor of ischaemic
      stroke. Several factors might contribute to the existing confusion--for example,
      small sample sizes, different ethnic groups, the influence of oestrogens in women
      participating in the studies, plasma storage before Lp(a) determination,
      statistical errors, and selection bias. This review focuses on the Lp(a) related
      mechanisms that might contribute to the pathogenesis of ischaemic stroke. The
      association between Lp(a) and other cardiovascular risk factors is discussed.
      Therapeutic interventions that can lower the circulating concentrations of Lp(a)
      and thus possibly reduce the risk of stroke are also considered.

PMID- 10961174
TI  - Flow cytometric immunophenotyping of serous effusions and peritoneal washings:
      comparison with immunocytochemistry and morphological findings.
AB  - AIM: To evaluate immunophenotyping by means of flow cytometry as a complementary
      method for the detection of malignant cells in serous effusions and peritoneal
      washings. MATERIAL AND METHODS: Frozen samples of 49 fresh serous effusions and
      peritoneal washings were analysed by flow cytometry, using monoclonal antibodies
      against CD45, Ber-EP4, and N-cadherin. Results were compared with smear and cell
      block morphology, as well as immunocytochemistry on paraffin wax embedded cell
      blocks. RESULTS: Seventeen specimens were cytologically diagnosed as malignant,
      whereas 25 were interpreted as benign. The remaining seven specimens were
      diagnosed as indeterminate or suspicious for malignancy. Ber-EP4 positive cells
      were detected in 16 of the 17 cytologically malignant effusions, as well as in
      five of seven suspicious cases and five of 25 specimens with benign cytology. In
      the latter group, three specimens showed atypical or malignant cell groups that
      were missed in routine morphological evaluation. In two additional samples,
      obtained from patients with benign and borderline ovarian tumours, Ber-EP4
      positive cells showed benign or mildly atypical features, and were interpreted as
      exfoliated benign or borderline malignant epithelial cells of tubal origin, or as
      endosalpingiosis. All five Ber-EP4 positive indeterminate specimens showed
      atypical or malignant cells on re-evaluation, and were Ber-EP4 positive in four
      of five cases using immunohistochemistry in cell block sections. Large numbers of
      CD45 positive and relatively few N-cadherin positive cells were detected in most
      specimens with the use of flow cytometry, when compared with morphological
      evaluation. CONCLUSIONS: Flow cytometry is a rapid and highly effective method
      for the evaluation of effusions and peritoneal washings. The detection of Ber-EP4
      positive cells using flow cytometry is strongly indicative of the presence of
      carcinoma cells in effusions and peritoneal washings. Although false positives
      are relatively infrequent, all specimens should be carefully evaluated
      morphologically to prevent the diagnosis of benign epithelial clusters as
      malignant.

PMID- 10961175
TI  - Immunohistowax processing, a new fixation and embedding method for light
      microscopy, which preserves antigen immunoreactivity and morphological
      structures: visualisation of dendritic cells in peripheral organs.
AB  - AIMS: To describe a new fixation and embedding method for tissue samples,
      immunohistowax processing, which preserves both morphology and antigen
      immunoreactivity, and to use this technique to investigate the role of dendritic
      cells in the immune response in peripheral tissues. METHODS: This technique was
      used to stain a population of specialised antigen presenting cells (dendritic
      cells) that have the unique capacity to sensitise naive T cells, and therefore to
      induce primary immune responses. The numbers of dendritic cells in peripheral
      organs of mice either untreated or injected with live Escherichia coli were
      compared. RESULTS: Numbers of dendritic cells were greatly decreased in heart,
      kidney, and intestine after the inoculation of bacteria. The numbers of dendritic
      cells in the lung did not seem to be affected by the injection of E coli.
      However, staining of lung sections revealed that some monocyte like cells
      acquired morphological and phenotypic features of dendritic cells, and migrated
      into blood vessles. CONCLUSIONS: These observations suggest that the injection of
      bacteria induces the activation of dendritic cells in peripheral organs, where
      they play the role of sentinels, and/or their movement into lymphoid organs,
      where T cell priming is likely to occur.

PMID- 10961176
TI  - Capacity for epithelial differentiation in synovial sarcoma: analysis of a new
      human cell line.
AB  - AIM: To analyse the capacity for epithelial differentiation in synovial sarcoma
      using a new human cell line. METHODS: A new human cell line, KU-SS-1, was
      established from a monophasic, spindle cell type of synovial sarcoma by grafting
      those cells on to severe combined immunodeficient (SCID) mice and then
      transferring them to in vitro culture systems. The KU-SS-1 cells were
      characterised by light and electron microscopy, and by immunohistochemical, flow
      cytometric, and cytogenetic analysis. RESULTS: Primary tumour and cultured cells
      at passage 20 showed a positive reaction for vimentin, which is a mesenchymal
      marker. After 40 passages, subcultured cells were injected into SCID mice to
      induce further tumours. These advanced subcultured cells and the tumour cells
      that they induced were positive for cytokeratin, an epithelial marker, and
      exhibited epithelial ultrastructural features such as intermediate junctions.
      Furthermore, two colour immunofluorescent analysis for proliferating nuclear cell
      antigen (PCNA) and intermediate filaments showed that a large number of PCNA
      expressing cells were positive for vimentin, and that part of this fraction also
      expressed cytokeratin. The existence of cells with reactivity for these three
      markers indicated that, in this cell line, a fraction with high proliferating
      capacity had both mesenchymal and epithelial markers. In addition,
      cytogenetically, this cell line expressed the SYT-SSX chimaeric transcript as a
      result of the t(X;18) (p11;q11) translocation. CONCLUSIONS: A human synovial
      sarcoma cell line was established and stably maintained in cell culture for more
      than 70 passages. In addition, this cell line showed epithelial differentiation,
      which supports the hypothesis that synovial sarcoma is a carcinosarcoma like
      tumour with true epithelial differentiation. This cell line will be a useful tool
      for investigating the nature of this tumour and will contribute to clinical
      studies.

PMID- 10961178
TI  - Preoperative histological classification of primary lung cancer: accuracy of
      diagnosis and use of the non-small cell category.
AB  - AIMS: To compare the preoperative classification of lung carcinoma made on
      cytological and histological specimens with the postoperative classification made
      on the resected specimen. In addition, to find out how often the term "non-small
      cell lung cancer, not otherwise specified" (NSCLC) was used, and in such cases to
      note the final diagnosis. METHODS: Between 1991 and 1995, 303 patients had a lung
      resection in Aberdeen for primary carcinoma. For each patient, the departmental
      records were examined for preoperative specimens (cytological and histological).
      A note was made of whether each specimen was positive or negative for malignancy
      and, if positive, what the cell type was. Where patients had more than one sample
      submitted, the most specific result was taken. RESULTS: Fifty four per cent of
      patients had a correct specific preoperative diagnosis of malignancy, whereas 34%
      were labelled as NSCLC. Patients with squamous carcinoma were more likely to have
      a diagnosis of malignancy (88%) that was specifically correct (75%). Patients who
      had adenocarcinoma were less likely to have a preoperative diagnosis of
      malignancy (64%) that was specifically correct (35%). For those in whom a
      diagnosis of NSCLC was made, 55% turned out to have adenocarcinoma whereas 24%
      had squamous carcinoma. CONCLUSIONS: By adhering strictly to criteria, a high
      accuracy of diagnosis can be achieved for squamous carcinoma, but the diagnosis
      of adenocarcinoma seems to be more of a challenge. NSCLC is a useful and
      appropriate classification, the use of which reduces the rate of inaccurate
      specific diagnosis. There are occasions when pathologists can provide a more
      accurate diagnosis by being less precise.

PMID- 10961177
TI  - Gastric mucosal inflammation and epithelial cell turnover are associated with
      gastric cancer in patients with Helicobacter pylori infection.
AB  - BACKGROUND: Infection with a virulent Helicobacter pylori strain is associated
      with gastric mucosal damage and the increased risk of gastric cancer. AIMS: To
      examine the characteristics of host gastric mucosal responses in patients with
      gastric cancer, histological grade of gastritis, gastric epithelial apoptosis,
      and proliferation were studied. METHODS: Thirty two patients with early gastric
      cancer and 32 sex and age matched controls were studied. All subjects were
      infected with a virulent H pylori strain (vacA s1/m1, cagA positive genotype).
      Biopsy specimens were taken from the antrum and the corpus of the stomach. The
      grade of gastritis was assessed according to the updated Sydney system. Apoptotic
      cells were detected using terminal uridine deoxynucleotidyl nick end labelling,
      and epithelial cell proliferation was determined by means of the Ki-67 labelling
      index. RESULTS: In patients with gastric cancer, significantly higher grades were
      observed when glandular atrophy (p < 0.05) and intestinal metaplasia (p < 0.01)
      were present in the antrum, and when mononuclear cell infiltration was present in
      the corpus (p < 0.05). The numbers of apoptotic cells were increased in patients
      with cancer (p < 0.05) and the apoptotic index correlated significantly with the
      grade of glandular atrophy. Epithelial cell proliferation was more likely to be
      increased in mucosa where intestinal metaplasia was present. CONCLUSIONS:
      Infection with H pylori causes increased gastric epithelial apoptosis, resulting
      in more severe glandular atrophy in patients with gastric cancer. Increased
      damage of gastric epithelial DNA and the presence of more severe atrophic
      gastritis might contribute to the development of gastric cancer.

PMID- 10961179
TI  - A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive
      individuals.
AB  - AIMS: To use laboratory data and liver biopsies, prospectively obtained from
      hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe)
      positive patients, for the assessment of: (1) the relation between biopsy
      length/number of portal tracts and sampling error; (2) the relation between the
      severity of piecemeal necrosis and the new grading terminology (minimal, mild,
      moderate, and severe chronic hepatitis); and (3) liver pathology, which has not
      been studied in patients with this specific serological profile. METHODS: The
      study group (n = 174) included 104 patients with normal aminotransferase
      concentrations and no cases with clinically apparent cirrhosis. The specimen
      length and number of portal tracts were measured at light microscopy examination.
      Sampling error analysis was related to the discrepancies between aminotransferase
      concentrations versus histological grade. Detailed histological scorings were
      undertaken by the reference pathologist and compared with laboratory and
      hepatitis B virus (HBV) DNA precore sequence data. RESULTS: Sampling error seemed
      to be a constant feature, even for biopsies > or = 20 mm, but increased
      dramatically in biopsies < 5 mm long and/or containing less than four portal
      tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity
      showed features of moderate and severe piecemeal necrosis, respectively. Ten per
      cent of the patients with normal aminotransferase values had stage III-IV hepatic
      fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core
      antigen expression was a strong predictor of high hepatitis B viraemia. There was
      no association between precore stop codon mutations, grade/stage of liver
      disease, and hepatitis B core antigen (HBcAg) expression. CONCLUSIONS: The
      specimen available for light microscopical examination should be > 5 mm long and
      should contain more than four portal tracts. In addition, the new grading
      terminology might give the clinician an inappropriately mild impression of the
      severity of piecemeal necrosis. Furthermore, even in the presence of normal
      aminotransferase concentrations, considerable liver pathology can be found in 10
      20% of HBsAg and anti-HBe positive individuals; such pathology is not associated
      with the occurrence of precore stop codon mutations.

PMID- 10961180
TI  - Silicone lymphadenopathy mimicking a lymphoma in a patient with a
      metatarsophalangeal joint prosthesis.
AB  - With lymph node enlargement, the possibility of a malignant process such as
      metastatic carcinoma or lymphoma needs to be excluded. This report describes a 47
      year old woman with inguinal lymph node enlargement initially suspicious for
      lymphoma. Fine needle aspiration findings favoured reactive hyperplasia, but a
      malignant process could not be excluded. The final histological diagnosis was a
      foreign body granulomatous inflammatory response as a result of regionally
      disseminated silicone particles from an over looked metatarsophalangeal joint
      prosthesis. Because of the large number of joint prostheses world wide, it should
      be kept in mind that migration of wear particles can create granulomatous
      inflammation and node enlargement.

PMID- 10961181
TI  - Small bowel haemangioma with local lymph node involvement presenting as
      intussusception.
AB  - Gastrointestinal haemangiomas make up 0.05% of all intestinal neoplasms. They are
      sometimes multiple and usually present with pain, bleeding, and obstruction. An
      associated haemangiomatous change in regional lymph nodes has not been reported
      previously. A woman of 21 years presented with abdominal pain and vomiting.
      Abdominal ultrasound and computed tomography scan showed a lower abdominal mass.
      Laparotomy revealed a small bowel tumour causing an intussusception together with
      enlarged mesenteric lymph nodes. Pathological examination revealed a small bowel
      haemangioma with mesenteric node involvement. The pathogenesis of haemangiomatous
      involvement of lymph nodes is discussed. Hamartomatous change is the likely cause
      in this patient.

PMID- 10961182
TI  - Oesophageal rhabdomyoma.
AB  - Extracardiac rhabdomyomas are rare benign tumours showing striated muscle
      differentiation. Seventy percent of these lesions occur in the head and neck
      region. The most common sites for these lesions are the larynx, pharynx, and the
      floor of the mouth. There has been only one previous report of a rhabdomyoma of
      the oesophagus; two further cases are described.

PMID- 10961183
TI  - Massive abdominal and pelvic myxoma in Carney's syndrome.
AB  - This report describes a massive abdominal and pelvic myxoma in a patient with
      Carney's syndrome. A 38 year old woman presented with abdominal distension and a
      palpable mass, and at operation a large pelvic and abdominal tumour was
      identified and resected. The surgical specimen consisted of a lobulated mass,
      which on cut section had a uniform gelatinous consistency. The mass surrounded
      both ovaries, the appendix, and the upper part of the uterus, but macroscopically
      did not appear to involve these organs. Histological examination showed plump
      stellate and spindle shaped cells set in an abundant myxoid stroma, in keeping
      with a myxoma. Immunohistochemical staining revealed positivity of tumour cells
      for vimentin, but no reactivity to desmin, alpha-smooth muscle actin, S-100
      protein, CD34, or AE1/AE3. This is the first documented case of massive adominal
      and pelvic myxoma in a patient with Carney's syndrome. Clinicians and
      pathologists should be aware that myxomas in Carney's syndrome can rarely involve
      unusual sites other than the skin and heart.

PMID- 10961184
TI  - Simultaneous occurrence of multiple aetiologies of polycythaemia: renal cell
      carcinoma, sleep apnoea syndrome, and relative polycythaemia in a smoker with
      masked polycythaemia rubra vera.
AB  - A 58 year old male heavy smoker presented with intracranial haemorrhage and
      erythrocytosis. Four aetiologies of polycythaemia--polycythaemia rubra vera
      (PRV), renal cell carcinoma, sleep apnoea syndrome, and relative polycythaemia-
      were found to be associated with the underlying causes of erythrocytosis. He did
      not fulfill the diagnostic criteria for PRV at initial presentation, but an
      erythropoietin independent erythroid progenitor assay identified the masked PRV,
      and the low post-phlebotomy erythropoietin concentration also suggested the
      likelihood of PRV evolution. This case demonstrates that a search for all the
      possible causes of erythrocytosis is warranted in patients who already have one
      aetiology of polycythaemia.

PMID- 10961185
TI  - Comparing substrates for the detection of ANAs.

PMID- 10961186
TI  - Pathological investigation of deaths following surgery, anesthesia and medical
      procedures.

PMID- 10961187
TI  - Comparing guidelines for the management of anogenital warts.

PMID- 10961188
TI  - AIDS and globalisation.

PMID- 10961189
TI  - Immunological basis of Chlamydia induced reactive arthritis.

PMID- 10961191
TI  - Recurrence of urogenital Chlamydia trachomatis infection evaluated by mailed
      samples obtained at home: 24 weeks' prospective follow up study.
AB  - OBJECTIVES: To evaluate the rate of recurrence of genital Chlamydia trachomatis
      infection after antibiotic therapy in a population of patients drawn from general
      practice, and to evaluate whether retesting after antibiotic therapy was
      advisable and, if so, whether it could be based on a strategy involving samples
      obtained at home and mailed to the laboratory for analysis. METHODS: Prospective
      follow up study of 42 patients with genital C trachomatis infection drawn from
      general practice. Patients at or above the age of 18, with a positive urogenital
      swab sample obtained by a general practitioner were invited to participate.
      Follow up testing was based on LCR testing (LCx, Abbott diagnostics) of first
      void urinary and vaginal flush samples taken by the patients at home and mailed
      to the laboratory at weeks 2, 4, 8, 12, and 24 after antibiotic therapy. RESULTS:
      Cumulated incidence of recurrent infection was calculated to 29% (95% CI: 12%
      46%) during the 24 weeks of follow up. Previous or present sexually transmitted
      diseases other than C trachomatis were significantly associated with recurrence
      (OR 6.1, p = 0.03). 89% of patients tested negative at week 2, and all patients
      tested negative at some point during the first 4-8 weeks. 84% of the test kits
      mailed to the patients were returned to the laboratory for analysis. CONCLUSIONS:
      Recurrence of C trachomatis after antibiotic treatment is a substantial problem.
      Retesting should be carried out, but not sooner than 12-24 weeks after treatment.
      Requiring patients to take tests at home appears to be a promising method for
      retesting.

PMID- 10961190
TI  - European course on HPV associated pathology: guidelines for primary care
      physicians for the diagnosis and management of anogenital warts.
AB  - The European Course on HPV Associated Pathology (ECHPV) was founded in 1990 by a
      group of clinicians, pathologists, and virologists to teach important principles
      for the practice and management of human papillomavirus (HPV) disease to
      gynaecologists, dermatologists, and other medical disciplines. These guidelines
      are intended to assist the practice of primary care physicians for diagnosis and
      treatment of anogenital warts.

PMID- 10961192
TI  - Assessment of Chlamydia trachomatis prevalence by PCR and LCR in women presenting
      for termination of pregnancy.
AB  - OBJECTIVES: To determine the prevalence of Chlamydia trachomatis in a patient
      population presenting for legal termination of pregnancy by polymerase chain
      reaction (PCR) and ligase chain reaction (LCR), from first catch urine and self
      administered tampons, and comparing with the traditionally collected endocervical
      swab tested by both PCR and culture. METHODS: Consecutive women attending for
      legal termination of pregnancy were screened for chlamydia by patient collected
      first catch urine and tampon, and physician collected endocervical swab. RESULTS:
      Of 1175 patients with complete samples, there were 33 (2.8%) in whom chlamydia
      was detected by two or more assays from one or more sample site. Chlamydia was
      detected equally well by both PCR and LCR in first catch urine (p = 0.25), tampon
      (p = 0.5), and endocervical swab (p = 0.5). However, both PCR and LCR were
      significantly better than culture of an endocervical swab (p = 0.0005) for
      detection of C trachomatis. CONCLUSION: The prevalence of chlamydia in patients
      presenting for termination of pregnancy was 2.8%. A simple efficient way of
      performing screening for chlamydia for women presenting for termination of
      pregnancy is by first catch urine or tampon, which can be tested by the highly
      sensitive amplification assays, PCR or LCR.

PMID- 10961193
TI  - Combined cervical swab and urine specimens for PCR diagnosis of genital Chlamydia
      trachomatis infection.
AB  - OBJECTIVES: Sampling of both the cervix and urine increases the chance of
      detection of Chlamydia trachomatis compared with sampling either site alone. We
      determined the effect of combining urine and cervical swab specimens in the
      clinic setting on the sensitivity of C trachomatis polymerase chain reaction
      (PCR) testing. METHODS: For each of 100 women attending a genitourinary medicine
      clinic with high likelihood of genital C trachomatis infection, one endocervical
      swab was placed in transport medium and another in one of two aliquots of first
      void urine. Four PCR assays per patient (urine + swab, swab alone, and urine
      alone both pre- and post-freeze-thawing) were processed by automated C
      trachomatis PCR (Cobas, Amplicor). An inhibition control was included with each
      assay to identify specimens containing PCR inhibitors. RESULTS: 71% of women were
      Amplicor C trachomatis PCR positive (according to the results of at least one
      specimen). PCR test results were concordant for 95/100 patients, and of the five
      discordant result sets there was only one major discrepancy. Inhibitors of PCR
      were present in 22/400 specimens from 20 patients, and 16/22 were cervical swabs
      (p < 0.001). CONCLUSIONS: Combining a cervical swab with a urine specimen is
      acceptable for PCR testing for genital C trachomatis infection, and has the
      potential to increase further the cost effectiveness of DNA based screening for C
      trachomatis genital infection.

PMID- 10961194
TI  - First episodes of genital herpes in a Swedish STD population: a study of
      epidemiology and transmission by the use of herpes simplex virus (HSV) typing and
      specific serology.
AB  - OBJECTIVES: To determine the proportion of herpes simplex virus type 1 (HSV-1)
      and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use
      of HSV specific serology for classifying first episodes of genital herpes and for
      defining HSV serostatus in the patients' sexual partners. METHODS: 108
      consecutive patients with first episodes of genital herpes seen at three STD
      clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and
      typing were performed and serum was tested for antibodies against a type common
      HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A
      structured interview including questions about sexual behaviour and sexual
      partners was taken. "Steady" partners were offered a blood test for HSV serology
      and counselling. RESULTS: Of 108 patients, 11 had a negative HSV culture. Of the
      97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97)
      as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was
      available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1
      infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the
      first episode of genital herpes corresponded to the first clinical recurrence of
      an infection acquired earlier in life. There was a significant correlation
      between having orogenital sex and being infected with HSV-1 and also a history of
      labial herpes in the partner. Only 20% of partners of patients with an HSV-2
      infection had a history of genital herpes. CONCLUSIONS: Almost half of first
      episodes of genital herpes are caused by HSV-1. In young women with a primary
      genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we
      found specific HSV serology of value for classifying first episodes and for
      diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported
      the suggestion that the orogenital route of transmission was common in genital
      HSV-1 infections.

PMID- 10961195
TI  - The burden of infection with HSV-1 and HSV-2 in England and Wales: implications
      for the changing epidemiology of genital herpes.
AB  - OBJECTIVE: To measure the burden of infection with herpes simplex type 1 (HSV-1)
      and herpes simplex type 2 (HSV-2) in the general population of England and Wales
      and to assess temporal changes in the incidence of HSV-1 infection in childhood.
      METHODS: 4930 residual blood samples taken from people aged 0-69 years and
      submitted to 15 public health laboratories in England and Wales between January
      1994 and June 1995, and 500 samples taken from people aged 10-14 years between
      November 1986 and December 1987, were screened for IgG antibody to HSV-1 and HSV
      2 using type specific ELISA assays. RESULTS: The prevalence of antibody to HSV-1
      in 10-14 year olds declined from 34% in samples collected in 1986-7 to 24% in
      samples collected in 1994-5 (p < 0.001). HSV-1 antibody prevalence in adults
      increased with age and was higher in females than males, reaching 54% in females
      aged 25-30 years in 1994-5. In samples collected in 1994-5 from people aged 16-69
      years HSV-2 antibody was detected in sera from 3.3% of men and 5.1% of women.
      CONCLUSIONS: The incidence of HSV-1 infection in childhood is falling in England
      and Wales. The prevalence of HSV-2 infection in the general population is low,
      with the rate of infection significantly lower than that described for the
      general population in the United States and developing countries. The falling
      rate of HSV-1 infection in childhood may be one factor contributing to the
      increasing incidence of genital HSV-1 infection.

PMID- 10961196
TI  - Report of sexually transmitted diseases by HIV infected men during follow up:
      time to target the HIV infected?
AB  - OBJECTIVES: To compare the rate of self reported sexually transmitted diseases
      (STDs) among HIV infected men with men who remained HIV negative during follow up
      of a Harare male factory cohort. METHODS: Male factory workers were offered
      enrolment and behavioural data were collected at entry then every 6 months, along
      with HIV testing. Self report of STDs was used to calculate incidence per 100
      person years. Cox proportional hazards models examined independent risk factors
      for STDs, with hazard ratios (HRs). RESULTS: At entry 20% of men were HIV
      infected and 11% reported STDs in the previous year. A total of 2777 (82%) of
      3383 men enrolled were followed at least once. Compared with men who remained HIV
      negative, seroconverters had the highest incidence of STDs (16.8 per 100 person
      years; IRR = 3.3, 95% CI = 2.5-4.3); men enrolled HIV positive also reported
      higher STD incidence (14.5 per 100 person years, IRR = 2.8; 95% CI 2.3-5.5).
      Among HIV positive men, the only independent risk factor for report of urethral
      discharge was history of multiple partners (HR = 10, 95% CI 1.4-73.2).
      CONCLUSION: HIV positive men reported threefold higher incidence of STDs than HIV
      negative men, many related to high risk sexual behaviour.

PMID- 10961197
TI  - Survival by AIDS defining condition in rural Uganda.
AB  - OBJECTIVES: To report the initial AIDS defining conditions, CD4 lymphocyte counts
      around the time of AIDS diagnosis, and survival by AIDS defining condition in a
      population based cohort in rural Uganda. METHODS: Participants in an HIV natural
      history cohort in rural Uganda were reviewed every 3 months at routine visits and
      at other times when they were ill. The date and nature of the first AIDS defining
      condition in participants developing AIDS during follow up between the start of
      the cohort in 1990 and the end of 1998 were noted. The CD4 count at, or within, 3
      months of this time was recorded for those participants who developed AIDS (WHO
      stage 4) after 1993. RESULTS: The median survival from developing AIDS to death
      was 9.3 months and the median CD4 lymphocyte count around the time of developing
      AIDS was 150 cells x 10(6)/l. The most frequent AIDS defining conditions were
      wasting syndrome, oesophageal candidiasis, and mucocutaneous herpes simplex virus
      infection (HSV) for more than 1 month. The median survival with wasting syndrome,
      Kaposi's sarcoma, and oesophageal candidiasis was less than 3.5 months; however,
      survival with cryptosporidial diarrhoea, chronic HSV, and extrapulmonary
      tuberculosis was greater than 20 months. There was little relation between CD4
      count around the time of development of the AIDS defining condition and the
      median survival with that condition. CONCLUSIONS: The survival for most AIDS
      defining conditions was generally shorter and the median CD4 lymphocyte count
      higher than studies reported from developed countries. However, the conditions
      with the longest survival (cryptosporidial diarrhoea, chronic HSV, and
      extrapulmonary tuberculosis) had a similar survival to that in developed
      countries and these conditions have a high background level in this population.

PMID- 10961198
TI  - Relation between information and advice provision to male GUM clinic attendees
      and sexual orientation and ethnic group.
AB  - OBJECTIVES: To examine whether the provision of advice and information to male
      genitourinary medicine (GUM) clinic attendees was related to their reasons for
      attendance, ethnicity, or sexual orientation. METHOD: Cross sectional survey of
      men attending a large city centre GUM clinic. Data were collected using an
      anonymous subject completed questionnaire. RESULTS: Of the 302 men recruited, 72%
      described themselves as white and 85% reported only female sexual partners.
      Information and advice provision were generally found to reflect reason for
      attendance--for example, those attending with a concern about "an STD or urinary
      problem" were more likely to report advice and information on NSU/chlamydia,
      herpes, gonorrhoea, or syphilis than those attending without such concerns. For
      those attending with a concern about HIV less than half (42%) reported receiving
      advice and information about HIV. The reasons for attendance were found to vary
      with ethnicity (black men were more likely to attend for a "check up," and less
      likely to attend about HIV or with genital warts than white men) and sexual
      orientation (those with male partners were more likely to attend about HIV or
      hepatitis B than those with only female partners); there were corresponding
      variations in the provision of advice and information. CONCLUSIONS: The clinic
      was generally providing advice and information appropriate to the reasons for
      attendance and this reflected variations in such needs with ethnicity and sexual
      orientation. The provision of advice and information about HIV could be more
      comprehensive.

PMID- 10961200
TI  - Prevalence of sexual dysfunction in new heterosexual attenders at a central
      London genitourinary medicine clinic in 1998.
AB  - OBJECTIVE: To determine the prevalence of sexual dysfunction and dissatisfaction
      (SD) among new heterosexual attendees at a central London genitourinary medicine
      (GUM) clinic. METHODS: Consecutive new attendees seen by a single clinician were
      asked a probe question about SD in the previous year. A clinical interview
      followed a positive response to the probe question. Demographic information was
      obtained using standard clinic forms. RESULTS: 37% of 103 men and 20% of 100
      women participants gave positive responses, and 24% of the men and 12% of the
      women wanted treatment for their problems. CONCLUSIONS: Our results indicate a
      relatively high rate of SD in new GUM clinic attendees that is not currently
      being detected or managed. SD may lead to psychological problems, which can be
      reversed with appropriate treatment. The financial implications of such treatment
      are discussed.

PMID- 10961201
TI  - Dorsal perforation of prepuce: a common end point of severe ulcerative genital
      diseases?
AB  - Severe ulcerative genital diseases can cause destruction of the prepuce, glans,
      or sometimes of the whole penis (phagedena). We observed a characteristic pattern
      of partial destruction of the prepuce as a result of a wide variety of ulcerative
      genital diseases. Five patients, two with severe genital herpes, one with
      hidradenitis suppurativa, and two with donovanosis presented with perforation on
      the dorsal surface of the prepuce. In four of them, the glans protruded through
      the defect and in one, the defect was not large enough to allow protrusion of the
      glans. In two patients, the preputial sac was obliterated. The relatively
      decreased blood supply of the prepuce is the probable explanation for perforation
      at this selective site.

PMID- 10961199
TI  - An intervention study to reduce adverse pregnancy outcomes as a result of
      syphilis in Mozambique.
AB  - OBJECTIVES: To create and evaluate an alternative screening approach among
      pregnant women in order to reduce adverse pregnancy outcome as a result of
      syphilis in Mozambique. METHODS: Four suburban antenatal clinics, two "control"
      and two "intervention" clinics, were compared regarding syphilis screening and
      treatment. Pregnant women with positive rapid plasma reagin (RPR) test (n = 929)
      were enrolled, 453 in the intervention and 476 in the control clinics. In control
      clinics the normal routine regarding syphilis screening was followed for 383
      women remaining for follow up. In intervention clinics nurse midwives were
      trained to perform the RPR test. RPR seropositive cases were immediately treated
      on site by the nurse midwives and the partners were invited to come any afternoon
      for treatment. In the third trimester (around 30 weeks) a new RPR test was
      performed and all women with positive RPR test results were again treated and the
      partners were invited to come for treatment. RESULTS: At delivery, the drop out
      rate was 15.7% in the intervention and 20.1% in the control group. The perinatal
      mortality was significantly higher in the control group than in the intervention
      group, 3.4% v 1.3% (p = 0.030). At delivery the intervention group had
      significantly more negative RPR results--40.9% v 24.2% (p = 0.000). CONCLUSION:
      More active training of nurse midwives in antenatal care to perform on site RPR
      tests, to give syphilis treatment, and to notify partners results in improved
      perinatal outcome and more seronegative parturient women.

PMID- 10961202
TI  - HSV-2 specific seroprevalence among various populations in Rome, Italy. The
      Italian Herpes Management Forum.

PMID- 10961203
TI  - Syphilis and gonorrhoea in the Baltic countries.

PMID- 10961204
TI  - Ethnic and demographic variations in HIV/AIDS presentation at two London referral
      centres 1995-9.

PMID- 10961205
TI  - Genital Chlamydia trachomatis infections in Lithuanian women invited for
      screening via newspaper advertisement: a pilot study.

PMID- 10961206
TI  - Pyogenic granuloma of the penis--don't squeeze them.
AB  - We report the case of a pyogenic granuloma on the shaft of the penis presenting
      with active bleeding secondary to attempted expression. Previously reported cases
      have documented such lesions on the prepuce and glans.

PMID- 10961207
TI  - Carbamazepine in Reiter's syndrome.

PMID- 10961208
TI  - Condoms and warts.

PMID- 10961209
TI  - Photosensitivity reaction of efavirenz.

PMID- 10961210
TI  - HIV associated cytomegalovirus retinitis in Melbourne, Australia.

PMID- 10961211
TI  - Azithromycin v oxytetracycline for the treatment of non-specific urethritis.

PMID- 10961212
TI  - Sexually transmitted infections in elderly people.

PMID- 10961213
TI  - Tertiary syphilis.

PMID- 10961214
TI  - [Treatment of malignant and benign biliary obstructions with metal stents].
AB  - The palliative treatment of malignant biliary tract obstructions using a metal
      stent is now an established procedure in clinical practice. An endoscopic,
      transpapillary approach is the first choice for implantation of the stent. If it
      is not possible to insert the stent in this way, which is often the case with
      high obstructions, a percutaneous approach is chosen. It appears to be beneficial
      to use a metal stent with a fine-meshed net such as, for example, the Wall stent.
      Metal stents have a higher patency rate than plastic stents so that the primary
      choice of a metal stent is justified. Coated stents have not yet shown any major
      advantages. In cases of stent occlusion, the coaxial implantation of a plastic
      stent seems to be the most efficient. In cases of benign biliary tract stenoses,
      a metal stent should only be implanted after a careful evaluation of all possible
      surgical modalities and exploitation of balloon dilatation and long-term
      splinting methods.

PMID- 10961216
TI  - [Cephalometric studies on X-ray pictures to evaluate postoperative cranial growth
      of children with craniosynostoses].
AB  - OBJECTIVE: A preoperative CT scan seems indispensible for the evaluation of the
      bones and soft tissue in children with craniosynostoses. Regular postoperative
      follow-up is limited because of general anaesthesia and radiation exposure.
      Therefore, cranial growth of these children has hardly been examined so far. A
      method is needed to replace CT for this indication and to allow differentiated
      growth analysis besides clinical inspection. METHODS: 15 children (7
      trigonocephalies, 4 plagiocephalies, 4 syndromal craniosynostoses) were operated
      on using a standardized bilateral fronto-orbital advancement. Using conventional
      pre- and postoperative skull roentgenograms, a craniometric analysis according to
      the modified method of Schmid et al. [13] was carried out. RESULTS: A supernormal
      opening of the frontal angle (the forehead area) and an increase of length of the
      frontal base were found. Skull height and skull width were positively influenced;
      the growth of the dorsal skull base remained retarded in length postoperatively.
      There was metrically identifiable reorganization of areas distant from operation
      area. Results were validated by comparison with normal subjects and patient
      populations known from the published literature. CONCLUSION: The presented method
      is easy, safe and exposure-reduced, and is able to assess the growth of different
      skull areas by means of distance and angle measurements. It should be used
      regularly in routine postoperative control of craniosynostoses. CT examinations
      should be limited to special questions of the soft tissue.

PMID- 10961215
TI  - [Aerosolized gadolinium-DTPA for demonstration of pulmonary ventilation in
      magnetic resonance tomography].
AB  - PURPOSE: Magnetic resonance assessment of lung ventilation with aerosolized Gd
      DTPA. METHODS: Eleven experimental procedures were carried out in a domestic pig
      model. The intubated pigs were aerosolized for 30 minutes with an aqueous
      formulation of Gd-DTPA. The contrast agent aerosol was generated by a small
      particle aerosol generator. Imaging was performed on a 1.5 T MR imager using a T1
      weighted turbo spin echo sequence with respiratory gating (TR 141 ms, TE 8.5 ms,
      6 averages, slice thickness 10 mm). Pulmonary signal intensities before and after
      ventilation were measured in peripheral portions of both lungs. RESULTS:
      Immediately after ventilation with aerosolized Gd-DTPA, the signal intensity in
      both lungs increased significantly in all animals with values up to 237% above
      baseline (mean 139% +/- 48%), but with in some cases considerable regional intra-
      and interindividual intensity differences. Distinctive parenchymal enhancement
      was readily visualized in all eleven cases with good spatial resolution.
      CONCLUSION: The presented data indicate that Gd-DTPA in aerosolized form can be
      used to demonstrate pulmonary ventilation in large animals with lung volumes
      comparable to man. Further experimental trials are necessary to improve
      reproducibility and to define the scope of this method for depicting lung
      disease.

PMID- 10961217
TI  - [MRI of aseptic osteonecrosis in children and adolescents with acute
      lymphoblastic leukemia].
AB  - PURPOSE: To evaluate the incidence, localisation, and course of symptomatic
      aseptic osteonecrosis (AON) in children undergoing treatment for acute
      lymphoblastic leukemia (ALL). METHODS: 72 MRI examinations obtained from 26
      children with bone pain selected from a group of 121 children with ALL were
      evaluated retrospectively. The area of the AON was determined by computer
      assisted planimetry. Follow-up examinations after 2-5 years were considered.
      RESULTS: 10/121 (8.3%) of the children had symptomatic AON, the number of lesions
      varied between 1 and 24 per child. 62/66 lesions were localized within the lower
      extremities. 58% of the AON were positioned in the epiphysis and 42% in the meta-
      and diaphysis. The mean area of AON was 7.6 cm2 with a range of 0.5 to 50 cm2.
      Follow-up examinations revealed a regression in 19 AON, no change in 43 and a
      progression in 4 lesions. AON within the epiphysis with joint involvement or
      lesions greater than 9 cm2 more frequently showed a progression of AON with final
      joint destruction. An elevated risk for AON was seen in children older than 10
      years and in children with intensified chemotherapy due to high-risk ALL.
      CONCLUSION: AON is a common complication in ALL-children under chemotherapy. Most
      frequently, the course is benign but large AON with joint involvement have an
      elevated risk for progression of AON with final joint destruction.

PMID- 10961218
TI  - [Volume-artifact reduction technique by spiral CT in the anterior, middle and
      posterior cranial fossae. Comparison with conventional cranial CT].
AB  - PURPOSE: The object of this study was to determine the extent to which a new
      volume-artifact reduction (VAR) modality using helical CT was able to reduce
      artifacts in the anterior, middle and posterior fossae in comparison with
      conventional CT (sequential mode). METHODS: In a prospective, randomized trial,
      50 patients underwent helical CT (VAR) and 50 underwent sequential CT. The
      results were evaluated by three radiologists; influences on image quality where
      scaled between 1 (no artifact) and 4 (not assessable). Eight regions of the
      anterior, middle and posterior fossae were evaluated. RESULTS: On average,
      artifacts were scaled at 2.5 in helical CT (VAR) and 3.1 in conventional CT.
      Significant differences were seen at the eyeball, anterior to the petrosal bone,
      at the internal occipital crest, and at the level of the transverse sinus (p <
      0.005). CONCLUSIONS: Helical CT with the VAR modality is superior to
      conventional, sequential CT in the area of the anterior, middle and posterior
      fossae.

PMID- 10961220
TI  - [Digital subtraction angiography of the extremities using step-translation
      technique].
AB  - PURPOSE: To evaluate, how routine application of i.a. DSA with the step
      translation technique using a single contrast bolus can effectively reduce
      radiation exposure and the amount of contrast media in comparison to standard
      peripheral DSA. METHOD/MATERIALS: 100 patients with peripheral arterial occlusive
      disease were assessed with step-translation DSA, 100 with standard DSA using the
      same equipment. Imaging quality was rated two observers, judgement by consensus.
      Comparison of the technical data (radiation dose, contrast media) was based on
      pairs of patients with similar constellations of stenoses to reduce selection
      bias. RESULTS: Step-translation DSA was of high imaging quality from the iliac
      vessels to the popliteal artery. In the distal leg, imaging was often impaired by
      effects like unilaterally delayed contrast flow due to high grade stenosis or
      motion artifacts. 53% of the step translation DSA required 1 or 2, 29% more than
      two additional DSA runs. Including the additional runs, the average radiation
      exposure and the amount of contrast media (2434 cGycm2/128 ml) were comparable to
      those of standard DSA (2461 cGycm2/144 ml). CONCLUSIONS: Step-translation DSA
      provides high quality images. In routine application realization of the
      advantages over standard DSA such as reduction of examination times, radiation
      exposure and amounts of contrast media may be impaired by poorly collateralized
      stenoses or motion artifacts demanding additional series.

PMID- 10961219
TI  - [Results of stereotactic breast biopsy in mammographically suspicious lesions].
AB  - PURPOSE: The object of this study was to evaluate the diagnostic accuracy of the
      stereotactic large core breast biopsy in the histological assessment of
      mammographically suspicious lesions. MATERIAL AND METHODS: In 106 patients with a
      mammographically suspicious lesion, 67 with a mass (55 non-palpable, 12 palpable
      and 39 with microcalcification stereotactic large core biopsies were performed.
      Samples were obtained in the prone position under local anesthesia with a 14
      gauge needle and an automated high-speed gun. An average of 4.3 cores per lesion
      were acquired. In 68 patients (64%) an additional surgical biopsy was performed,
      38 (36%) had clinical and mammographic follow-up. RESULTS: In 4 of the 106
      stereotactic biopsies insufficient material for the histological examination was
      obtained. In the 68 core biopsies with surgical correlation there were no false
      positive, but 2 false-negative results with regard to the malignancy of the
      lesion (sensitivity: 93.8%; specificity: 100%). The 2 false-negative results were
      obtained in lesions that were mammographically judged as malignant while
      histology of the stereotactic biopsy showed fibrosis. The stereotactic large core
      breast biopsy was well tolerated by all patients. No clinically significant
      complications occurred. CONCLUSION: The stereotactic large core breast biopsy of
      a mammographically suspicious lesion can be performed with a high diagnostic
      accuracy. A correlation of the mammographic and histological findings and a
      follow-up program are necessary in order to recognize false-negative results
      early and to avoid a delay in the diagnosis.

PMID- 10961221
TI  - [Comparison of contrast harmonic imaging in B-mode with stimulated acoustic
      emission, conventional B-mode US and spiral CT in the detection of focal liver
      lesions].
AB  - PURPOSE: Comparison between contrast harmonic imaging (CHI) in B-mode with
      stimulated acoustic emission (SAE), conventional B-mode US, and spiral CT in the
      detection of focal liver lesions. METHODS: In this pilot study 26 patients with
      liver lesions diagnosed by B-mode US and contrast-enhanced spiral-CT were
      additionally examined with CHI in B-mode. Each examination started with a bolus
      injection of 4 g of the US contrast agent Levovist (300 mg/ml) after a delay of
      at least 5 minutes to ensure liver-specific phase. All examinations were
      documented on video tapes and analysed by two radiologists. RESULTS: 81 liver
      lesions were diagnosed with both US examinations and spiral CT. B-mode US
      detected 66 lesions, CHI with SAE 72 lesions, and spiral CT 73 lesions. Compared
      to spiral CT 8 lesions in 3 patients could be depicted additionally with both US
      methods. Metastases and HCC present in CHI with SAE as not-enhancing signal
      contrast agent areas. Delineation of haemangiomas and FNH was often worse
      compared to the native examinations. CONCLUSION: The new US method CHI with SAE
      depicted more lesions than conventional B-mode US and is in some cases superior
      to spiral CT.

PMID- 10961222
TI  - [Functional MR-pancreatography with secretin. A comparison of imaging quality and
      diagnostic value].
AB  - PURPOSE: The aim of the present study was to assess imaging improvement and
      diagnostic value of secretin stimulated MR-pancreatography (MRP) compared to
      conventional MRP. MATERIALS AND METHODS: 50 patients were studied with a 1.0 T
      system using a single-shot-TSE sequence (RARE). Imaging quality and diameter of
      the different parts of the pancreatic tract and diagnoses were monitored before
      and after secretin. RESULTS: The visualization of the normal main pancreatic duct
      (MPD) was improved significantly in head, body and tail. Side branches were not
      depicted at all. Even in chronic pancreatitis a significant improvement of
      imaging quality could be observed, but only in patients without duct dilation
      before secretin. In advanced disease with duct dilation, secretin stimulation
      provided no further diagnostic improvement. CONCLUSIONS: In conclusion, secretin
      increases the diagnostic value of MRP especially in patients with normal or non
      dilated native MPD and may help to avoid unnecessary invasive procedures such as
      ERCP.

PMID- 10961223
TI  - [CT-guided biopsies, drainage and and percutaneous gastrostomies: comparison of
      punctures with and without CT fluoroscopy].
AB  - PURPOSE: The purpose of this prospective and randomized study was to compare two
      CT guidance techniques (CT-fluoroscopy/conventional CT) on percutaneous biopsies,
      drainages and gastrostomies. MATERIAL AND METHODS: 78 CT-guided interventions (29
      biopsies, 38 drainages, 8 gastrostomies) were recorded and the Mann-Whitney U
      test was applied. In 3 cases both guidance techniques were used. Procedure times,
      yields and radiation doses were analyzed. RESULTS: All 38 drainages and all 8
      gastrostomies were successfully applied. 13 biopsies with conventional CT
      guidance (n = 15) and 13 biopsies with CT-fluoroscopy (n = 14) showed a
      representative histopathologic result. The procedure times were not significantly
      different (drainages: p = 0.658, biopsies: p = 0.431, gastrostomies: p > 0.06).
      The radiation doses (CTID1) of the biopsies and drainages showed significantly
      higher values (drainages p < 0.001, biopsies p < 0.001) with CT-fluoroscopy than
      with conventional CT. There were no significant differences in gastrostomy
      procedures (p > 0.06). CONCLUSION: Procedure times and yields were not improved
      by using CT-fluoroscopy. Radiation doses showed significantly higher values with
      CT-fluoroscopy than with conventional CT guidance. CT-fluoroscopy was
      advantageous in non-compliant patients over conventional CT guidance.

PMID- 10961224
TI  - [Mid-term follow-up after placement of the new balloon-expendable VIP-stent into
      the iliac arteries].
AB  - PURPOSE: To assess the effectiveness and mid-term patency of VIP balloon
      expandable stents in patients with iliac occlusive disease. MATERIAL AND METHODS:
      Between August and December 1997, 26 balloon-expandable VIP (Medtronic) stainless
      steel vascular stents were implanted in 19 patients with iliac occlusive disease.
      22 lesions in common iliac (n = 11), external iliac (n = 5), common iliac plus
      contralateral external iliac (n = 1), and unilateral common and external iliac (n
      = 2) arteries were stented, allowing 20 limbs for assessment. There were 18
      stenoses and 4 occlusions in 7 female and 12 male patients (mean age 65 years,
      range 45-80). RESULTS: All lesions were treated satisfactorily, yielding a
      technical success rate of 100%. Primary patency was 91% (20/22) at 6 months. In 2
      lesions restenoses (90% and 70%) were observed, requiring repeated angioplasty.
      Color Doppler analysis at 12 months revealed no further restenoses. CONCLUSION:
      The new VIP balloon-expandable stents achieve very good initial technical success
      and good mid-term patency in the treatment of iliac occlusive disease.

PMID- 10961225
TI  - [Reduction of radiation dosage by using digital luminescence radiography on a
      hand phantom].
AB  - PURPOSE: How much can the radiation dose be reduced for hand radiography by using
      digital luminescence radiography (DLR)? METHODS AND MATERIALS: A hand phantom
      (3M) with a cyst, two fractures and an "amputation" was digitally exposed in an
      anterior-posterior orientation using DLR (ADC-70, Agfa). The tube current time
      product (mAs) was reduced gradually while keeping the voltage constant. The
      surface entrance dose was measured by a Dosimax sensor (Wellhofer). Five
      investigators evaluated the images for characteristics and critical features,
      pathological findings, visual resolution and contrast. RESULTS: The surface
      entrance dose at 50 kV/5 mAs was 31 microGy. The images could be evaluated very
      well down to an average dose of 36% (11 microGy); sufficient images were obtained
      down to an average dose of 26% (8 microGy). The resolution of the line pairs was
      the same or reduced by 1 level depending on the investigator. Contrast was
      assessed as being very good to sufficient. CONCLUSION: For the sufficient
      exclusion of a fracture the dose can be reduced to at least 39%, for the
      sufficient assessment of bony union and possible inflammatory changes to at least
      42%, to position check and foreign body search to at least 23%. By DLR the
      following question-referred mAs-product at 50 kV are stated: fracture exclusion 2
      mAs, bony union, arthritis and osteomyelitis 2.2 mAs, position check and foreign
      body search 1.25 mAs.

PMID- 10961227
TI  - [Massive cerebral hemorrhage: fistula of the dura from atypically originating A.
      meningea media].

PMID- 10961226
TI  - [X-rays taken by radiologists! Influence on a continuous quality improvement
      process?].
AB  - PURPOSE: To evaluate how the training of radiology residents in taking
      radiographs influences the work of radiographers and the established quality
      standards. METHODS: A first year radiology resident was trained for 4 weeks in
      focusing and exposure techniques by radiographers. In a second period the
      resident took 582 radiograms, which were compared with those taken by technicians
      for error estimation on a daily basis. During a third period the radiographs were
      produced in a contest between the resident and a skilled radiographer. Errors
      were analyzed by two independent experts according to established guidelines of
      the German Medical Association. RESULTS: At the beginning of the second period
      the average error rate of the resident was 11.9% as compared to 8.9% in the
      technicians team, in the following month 9.2% versus 15.9%. In the third period
      no relevant difference in errors could be observed. Finally, unexpected quality
      improvements were implemented like an improved standardization of focusing and
      exposure techniques as well as dose reduction. CONCLUSIONS: Radiology residents
      easily learn focusing and exposure techniques and achieve comparable results as
      radiographers within a short period of time. The additionally achieved knowledge
      improves the technical process of taking radiographs. We recommend to include a
      two plane radiography training period in the curriculum of radiology residents.
      It reinforces the radiologist's role in continuous quality improvements of the
      diagnostic process.

PMID- 10961228
TI  - [Missing hemodynamic response in retained neuronal function: pitfall of
      functional MRT in patients with stenosing vascular processes].

PMID- 10961229
TI  - A mother's reaction to a rebellious adolescent.
AB  - Written by the mother of a teenage girl, the opening article illustrates the
      struggles and frustrations faced by troubled adolescents and their families. This
      article might benefit physicians dealing with families that have similar
      problems.

PMID- 10961230
TI  - Basic neuroscience: critical issues for understanding psychiatric disorders.
AB  - Recent scientific advances in understanding the function and plasticity of the
      central nervous system have opened fundamental insights into the pathophysiology
      of various mental disorders. This chapter reviews the basic physiology of the
      central nervous system, and further focuses on the applications of the new
      knowledge to clinical psychiatry.

PMID- 10961231
TI  - An update on adolescent psychopharmacology.
AB  - Adolescent pediatricians are being asked to assume a larger role in the
      management of psychiatric disorders. Therefore, dissemination of the knowledge
      base regarding the use of psychotropic medications to treat these disorders in
      children and adolescents is critical. This chapter is an update to the previous
      "Primer on Adolescent Psychopharmacology" by Bailey and Hendren. Many of the
      disorders that occur in adolescence are associated with significant morbidity and
      functional impairment. While the evaluation of adolescents involves a careful
      assessment of the psychosocial milieu and the implementation of an intervention
      that involves the use of multiple modalities, pharmacotherapy can diminish
      symptom severity and thereby assist in the process of recovery. Successful
      pharmacotherapy begins with the development of an active and reciprocal alliance
      with the patient and family that allows for sharing of critical information and
      provision of support. The initiation of treatment should include a clear
      definition of target symptoms, the potential risks and benefits of the proposed
      intervention, and a discussion that includes a review of the current treatment
      experiences in both adult and child psychiatry. The establishment of a method
      that allows for adequate monitoring of both response and side effects is
      critical. Clearly, this is a field in its infancy. Thus, practitioners must be
      acutely aware of both the extent and limitations of the existing knowledge base
      as well as critical need for more controlled studies of these interventions in
      adolescence.

PMID- 10961232
TI  - A private practitioner's approach to adolescent problems.
AB  - This chapter presents an approach to caring for adolescent problems in a practice
      situation and addresses many important adolescent issues. It highlights the
      importance of establishing a trusting and confidential relationship with
      adolescents, offers guidelines for conducting routine adolescent visits and
      formal psychosocial evaluations, and emphasizes the importance of collaboration
      with other practitioners and mental health professionals.

PMID- 10961233
TI  - Pediatricians' pet peeves about mental health referrals.
AB  - This chapter has described a number of problems encountered by pediatricians when
      referring their patients for mental health services; these are related to access
      to care, quality of providers and service, attitudes of patients and providers,
      and lack of adequate communication. We have discussed some of the reasons for
      these difficulties, provided information that may assist pediatricians in making
      referrals to appropriate mental health providers, and offered suggestions to
      facilitate the referral process. We have highlighted the utility of developing
      and maintaining a relationship with mental health referral sources, and noted a
      number of advantages of including mental health providers in pediatric practices.

PMID- 10961234
TI  - Societal exploitation.
AB  - Societal exploitation has produced a significant increase in stress-related
      adolescent problem behaviors. The author explores the attributes of contemporary
      society, changes in the role and function of families, and how the changing times
      may have increased the pressure on the adolescent population.

PMID- 10961235
TI  - Practical and emotional consequences of parental divorce.
AB  - This review explores divorce as a risk factor for psychological problems among
      children and adolescents and the difficult emotional and practical transitions it
      creates for them. The authors provide helpful suggestions for primary care
      pediatricians on how best to assist their adolescent patients and their families
      in dealing with the transition.

PMID- 10961236
TI  - Diet and adolescent behavior: is there a relationship?
AB  - Behavioral problems such as hyperactivity, learning disabilities, mental illness,
      aggressive and antisocial behavior, and juvenile delinquency have been
      purportedly linked to the potential influence of foods or nutrients. This article
      examines the scientific evidence of the relationship between food and behavior in
      children and adolescents. It highlights the implications for practitioners
      important to consider in the assessment of the relationship between diet and
      behavior.

PMID- 10961237
TI  - Adolescent cigarette smoking: prevalence, causes, and intervention approaches.
AB  - Cigarette smoking continues to be a major public health problem that specifically
      affects the adolescent population. This chapter discusses current prevalence
      rates, recent trends, and the etiology of adolescent smoking, as well as
      strategies for preventing or reducing it. The authors highlight the prevention
      approaches demonstrated to effectively influence smoking behavior, such as those
      that teach adolescents social resistance skills and antismoking norms alone or in
      combination with teaching overall personal and social skills.

PMID- 10961238
TI  - Cultural and medical issues of Latino adolescents.
AB  - While the cultural and medical issues of providing care to immigrants have been
      primarily addressed in the adult literature, this article discusses how these
      issues concern Latino adolescents. Recognizing the multitude and complexity of
      immigrant experiences and responses to the acculturation process, the authors
      address myths and stereotypes associated with Latino culture that interfere with
      health care delivery.

PMID- 10961239
TI  - Displaced children: meeting the health, mental health, and educational needs of
      immigrant, migrant, and homeless youth.
AB  - A growing number of children of all ages are experiencing homelessness and
      displacement. This chapter explores the needs of displaced children in the U.S.,
      focusing on children of immigrants, children from families of migrant
      farmworkers, and homeless youth. The author discusses many of the common
      challenges and needs of displaced youth, but also points out the differences
      between younger children and adolescents, followed by a set of recommendations
      for health care and service providers.

PMID- 10961240
TI  - Early identification of emotional and behavioral problems in a primary care
      setting.
AB  - Adolescence is a time when many psychiatric disorders first manifest themselves.
      The challenge to pediatricians is to recognize early signs of behavioral problems
      in their adolescent patients. This review suggests several practical approaches
      to the detection, assessment, and treatment of emotional problems in adolescents
      within the time limits of a typical pediatric exam. The approaches presented
      range from general health supervision of all adolescents to more intensive
      evaluation of at-risk adolescents.

PMID- 10961241
TI  - Depression in the adolescent patient.
AB  - Depression in adolescence is a major public health problem that is associated
      with significant morbidity and mortality. A large number of clinically depressed
      adolescents still are unrecognized and untreated. This chapter provides
      pediatricians with useful guidelines for recognizing and managing adolescent
      depression in a primary care setting.

PMID- 10961242
TI  - The adolescent with conduct disorder.
AB  - Conduct disturbances are some of the most prevalent, enduring, impairing, and
      costly problems of childhood and adolescence. Despite many advances in our
      understanding of these disorders, they still remain a problem for the
      individuals, families, and society alike. Large-scale, multifaceted efforts are
      needed within our schools and communities if we are to have an impact on the
      prevalence and progression of these very problematic disturbances.

PMID- 10961243
TI  - Attention deficit hyperactivity disorder.
AB  - A large percent of children with attention deficit hyperactivity disorder (ADHD)
      continue to have ADHD in adolescence. Additional problems typically associated
      with developmental changes that occur by adolescence complicate the clinical
      picture and the challenges for practitioners. This comprehensive review will
      undoubtedly assist practitioners in acquiring a better understanding of
      contemporary approaches to conceptualizing, diagnosing, and treating adolescents
      with ADHD.

PMID- 10961244
TI  - Firesetting.
AB  - Firesetting results in a significant loss of life and property in the U.S. Child
      and adolescent firesetting accounts for a large percent of all firesetting
      occurrences. This article reviews the etiology and prevalence of firesetting in
      adolescence, presents case studies, and discusses approaches to management,
      therapy, and prognosis of adolescent firesetters.

PMID- 10961245
TI  - Early identification of schizophrenia.
AB  - Schizophrenia is a potentially disabling mental disorder that often runs a
      chronic or recurrent course and represents a major public health problem. Most
      forms of schizophrenia first manifest themselves in late adolescence and early
      adulthood. Accurate early diagnosis and prompt intervention can help to diminish
      the negative consequences of this disorder. This comprehensive review covers all
      aspects of early diagnosis of schizophrenic disorder in adolescents.

PMID- 10961246
TI  - Psychological problems manifested by somatic symptoms.
AB  - Physicians often encounter patients with somatic symptoms that reflect a wide
      range of life difficulties and psychological problems. This review covers common
      somatic symptomatology in adolescents, diagnosis and management of somatoform
      disorders, somatic presentations of other major psychiatric disorders, and
      discusses ways of approaching and screening for difficulties in adolescent
      populations.

PMID- 10961247
TI  - Diagnosis and management of rheumatic diseases in adolescence.
AB  - The rheumatic diseases constitute a significant group of chronic illnesses
      affecting children of all ages, including adolescents. This chapter provides an
      overview of rheumatic diseases and medical treatment options. Issues of sexuality
      and self-image that may influence treatment course and outcome are explored. The
      author emphasizes the importance of cooperation and communication between patient
      and physician, which enable adolescents to participate in the design and
      maintenance of their regimens.

PMID- 10961248
TI  - Etiology and pathogenesis of rheumatic diseases of adolescence.
AB  - The pathogenesis of SLE is multifactorial. Immune complexes, autoantibodies, and
      abnormal T-lymphocyte responses all play a part. Genetic predispositions are
      present, but not as strongly expressed as in the spondylarthropathies.
      Environmental agents and the effects of sex hormones also contribute.

PMID- 10961249
TI  - The current use and interpretation of rheumatologic tests.
AB  - The growing emphasis on primary care medicine has led to an increase in the
      number of physicians ordering and interpreting tests previously used by
      specialists. In order to prevent unnecessary and inaccurate testing, it is
      important to determine the necessity and accuracy of a test before it is
      performed. This chapter reviews several types of autoantibody (ANA) tests
      sensitive to rheumatologic diseases and explains how such tests may aid
      diagnosis.

PMID- 10961250
TI  - Polymerase chain reaction as a diagnostic tool.
AB  - Although the method of polymerase chain reaction (PCR) is technical, the concept
      is simple: PCR is a sequential process that explores a sample for the presence of
      a known sequence of DNA or RNA. Chapter sections cover specific applications of
      PCR to infectious diseases with rheumatic manifestations.

PMID- 10961251
TI  - Juvenile rheumatoid arthritis and the spondyloarthropathies.
AB  - Juvenile rheumatoid arthritis (JRA) and the spondyloarthropathies affect
      approximately one in a thousand children under the age of 17 years and are more
      common than diabetes, cystic fibrosis, and many other chronic conditions. The
      author explores differential diagnoses for musculoskeletal pain, classifies types
      of JRA and the spondyloarthropathies, and describes how such conditions may be
      effectively managed with drug and physical rehabilitation therapy. The article
      also discusses behavioral, school, and vocational issues.

PMID- 10961252
TI  - Caring for the adolescent with systemic lupus erythematosus.
AB  - Nearly 15% of patients with systemic lupus erythematosus (SLE) present during
      adolescence; it is therefore highly likely that a pediatrician will care for a
      young adult with SLE in his or her practice. The author stresses the importance
      of an individualized medical treatment plan that suits the patient and disease
      stage, as well as the clinician's obligation to provide clear and accurate
      information to adolescents and their parents. Guidelines to facilitate patient
      compliance and understanding are also offered.

PMID- 10961253
TI  - Other rheumatic diseases in adolescence. Dermatomyositis, scleroderma, overlap
      syndromes, systemic vasculitis, and panniculitis.
AB  - In addition to juvenile rheumatoid arthritis (JRA) and systemic lupus
      erythematosus (SLE), dermatomyosytis, scleroderma, overlap syndromes, systemic
      vasculitis, and panniculitis also present in adolescence. The authors discuss the
      complex epidemiology, diagnosis, clinical features, diagnostic testing,
      treatment, and prognosis of these diseases.

PMID- 10961254
TI  - Dermatologic manifestations of rheumatic diseases.
AB  - Cutaneous manifestations, potential sources of major discomfort, anxiety, and
      concern often coexist with or precede symptoms of systemic features of rheumatic
      diseases in children and adolescents. This chapter identifies skin features that
      may indicate rheumatologic disorders and describes various treatments and
      management approaches for cutaneous features.

PMID- 10961255
TI  - Progress in diagnosis and understanding chronic pain syndromes in children and
      adolescents.
AB  - The frequency of chronic pain syndromes in pediatric rheumatology has increased
      over the past 25 years. Diagnosis is complex: underlying organic illness,
      somatization, and growing pains are all possibilities. The author reviews pain
      studies involving children and adolescents, offers guidelines to classify chronic
      pain syndromes, and describes different pain modalities.

PMID- 10961256
TI  - Infectious causes of arthritis in adolescents.
AB  - Although most joint pain in adolescents is secondary to injury, inflammatory
      arthritis, mechanical problems, and other causes, infectious causes of arthritis
      should always be considered. Infections may cause arthritis by direct infection,
      reactive disease, or immune-mediated mechanisms. This chapter reviews common
      infectious causes of arthritis and also recognizes the difficulties in
      distinguishing categories.

PMID- 10961257
TI  - Renal manifestations of rheumatic diseases affecting adolescents.
AB  - Because of complex immunologic, renal, infectious, fertility, and psychological
      issues, renal disease secondary to rheumatic disease represents one of the most
      challenging medical problems for subspecialist and primary care physician alike.
      However, adolescents with renal disease respond better to treatment than do
      adults. This chapter addresses the renal manifestations of rheumatic diseases,
      current treatment options, and complications associated with treatment and long
      term prognosis.

PMID- 10961258
TI  - The respiratory system in connective tissue diseases.
AB  - Adolescents with connective tissue diseases (CTDs) are at risk for community
      acquired and opportunistic respiratory tract infections; it is mandatory to
      consider an infectious etiology in the differential diagnosis. The authors
      highlight the respiratory manifestations of the more common CTDs seen in
      adolescence, and also discuss useful diagnostic tests and drug regimens.

PMID- 10961259
TI  - Medical treatment of adolescents with rheumatic disease.
AB  - Although medication has yet to cure rheumatic disease, over the past two decades
      many adolescent patients have had improved quality of life with better control of
      pain, deformity, and weakness. However, noncompliance resulting from risk-taking
      behavior and concerns about cosmetic side effects and fertility may reduce the
      effectiveness of any drug regimen. The author reviews commonly used medications
      and their indications and side effects, and includes a section about the effect
      of pregnancy on rheumatic disease.

PMID- 10961260
TI  - Psychosocial aspects of rheumatic disease in childhood and adolescence.
AB  - The increasing number of adolescents with disabilities such as systemic lupus
      erythematosus who survive into adulthood has prompted the medical community to
      study the psychological and physical functioning of adolescents after many years
      of chronic illness. The author uses a generic chronic illness model to augment
      observations from studies about young people with rheumatic disease.

PMID- 10961261
TI  - Threats to chronically ill adolescents. Challenges for physicians as we approach
      the next millennium.
AB  - The frequency of all forms of juvenile arthritis, including juvenile rheumatoid
      arthritis, other major connective tissue diseases, and other rheumatic diagnoses,
      is estimated to be approximately 160,000-190,000 U.S. children under 15 years of
      age. The author suggests that the legitimization of alternative medicine and the
      corporatization of U.S. health care are undermining the quality of care that
      chronically ill adolescents receive.

PMID- 10961262
TI  - A commentary on Newman: theory of health as expanding consciousness.

PMID- 10961263
TI  - Religion, gender, and autonomy: a comparison of two religious women's groups in
      nursing and hospitals in the late nineteenth and early twentieth centuries.
AB  - Modern historical research of women and nursing has largely neglected the role of
      religious groups, particularly in the American frontier. The image of women at
      the end of the 19th century was one of submission to male authority and
      confinement to the domestic sphere. However, in the pluralistic West, a variety
      of organized religious women built and administered hospitals, initiated
      professional nursing, and provided effective health care services. This article
      compares cases of Catholic nuns and Mormon women as exemplars in a conceptual
      context of religious devotion, gender roles, and autonomy among women's religious
      organizations at the dawn of the 20th century.

PMID- 10961264
TI  - The politics of health promotion: influences on public health promoting nursing
      practice in Ontario, Canada from Nightingale to the nineties.
AB  - The marked and significant differences in the various meanings ascribed to health
      promotion in professional literature provide evidence of the concept's evolution
      over the last half of the 20th century and testify both to the powerful
      influences of dominant ideologies and the invisibility of others. The "new public
      health" marks a return to a conceptualization of health that is consistent with a
      nursing paradigm and thus potentially useful in supporting nursing health
      promotion practice. To take full advantage of this knowledge, however, it is
      critical that nurses reclaim their legacy in health promotion, critically
      appraise outside influences that threaten to undermine their work, and educate
      the public and other disciplines about nursing's unique focus on health
      promotion.

PMID- 10961265
TI  - "Nurses as health evangelists"?: The evolution of public health nursing in
      Canada, 1918-1939.
AB  - Public health nurses provided leadership for the advancement of public health in
      Canada in the early decades of this century, although leadership by nurses is not
      celebrated in public health history. The historical period (1918-1939) selected
      for this inquiry is one in which public health nurses created a legacy of
      achievements in public health nursing education, practice, and the organization
      of community health services within the most challenging of social, economic, and
      political contexts. The practice of public health nursing in Canada during the
      interwar years included strategies that were then and still are integral to the
      discipline--those of forming connections with the community, providing leadership
      in the public health movement, and facilitating community organization. It is
      vital to understand the significance of these origins of public health nursing as
      forces in the present context of practice threaten to alter fundamentally the
      nature of public health nursing's connection with the community. The purpose of
      this article is to highlight aspects of this historical legacy so that its
      influence can be more fully understood and strengthened in current health system
      transitions.

PMID- 10961266
TI  - Venous envy: the post-World War II debate over IV nursing.
AB  - After World War II, a debate ensued over whether nurses should perform
      intravenous (IV) therapy. The debate was resolved by permitting nurses to do
      venipunctures as physicians' agents and by recirculating the familiar tautology:
      if nurses were already doing venipunctures, they must be simple enough for nurses
      to do. The vein was a portal of entry for nurses, but one with limited access.
      What was ultimately ceded to nurses was not full jurisdiction over a domain of
      nursing practice, but rather a limited settlement in a domain of medical
      practice. The debate over IV therapy demonstrated how technology, in combination
      with ideology, can both create and destroy nursing jurisdictions.

PMID- 10961267
TI  - Creating critical care: the case of the Hospital of the University of
      Pennsylvania, 1950-1965.
AB  - This article examines the development of critical care nursing from 1950 to 1965
      through the lens of a local story--the development of the critical care unit at
      the Hospital of the University of Pennsylvania (HUP) in Philadelphia,
      Pennsylvania. The methodology used is social history. The data for the analysis
      were derived from oral history interviews, archival material, and secondary
      sources. The study concludes that powerful social contextual factors, such as
      work force and economic issues, architectural changes, and an increasingly
      complex hospital population--rather than new technology--supported the
      development of critical care. The study also provides parallels to contemporary
      nurse work force issues.

PMID- 10961268
TI  - Patterns of ideas in the professional life and writings of Karin Neuman-Rahn: a
      biographical study of the ideas of psychiatric care in Finland in the early
      twentieth century.
AB  - This study aims to increase the understanding of ideas in Finnish psychiatric
      care, based primarily on texts produced by Karin Neuman-Rahn (1867 through 1962)
      and anchored in the history of ideas within the period in question. The main
      pattern encompasses the idea of vocation and service, good spirit, caring
      culture, and bodily care of the mentally ill. Her texts reflect a profound
      ethical stance, an understanding of mental life, mental suffering, the power of
      human will, and the idea of the possible. The research indicates that history
      offers much valuable wisdom that we can incorporate from history.

PMID- 10961269
TI  - Radiographic contrast media.

PMID- 10961270
TI  - Ultrasonographic contrast media in the urinary tract.

PMID- 10961271
TI  - Radionuclides in the investigation of the urinary tract.

PMID- 10961272
TI  - Ultrasonography and Doppler studies in the diagnosis of renal obstruction.

PMID- 10961273
TI  - Helical computed tomography in the diagnosis of ureteric colic.

PMID- 10961274
TI  - Magnetic resonance urography.

PMID- 10961275
TI  - Spiral computed tomography in the diagnosis of renal masses.

PMID- 10961276
TI  - Magnetic resonance in the diagnosis of renal masses.

PMID- 10961277
TI  - Imaging in acute renal infection.

PMID- 10961278
TI  - Towards an understanding of urinary tract infection in children: a model for the
      future of paediatric radiology and urology.

PMID- 10961279
TI  - Comparison of imaging methods for renal artery stenosis.

PMID- 10961280
TI  - Adrenal imaging.

PMID- 10961281
TI  - Bladder cancer staging.

PMID- 10961282
TI  - Prostate cancer staging using imaging.

PMID- 10961283
TI  - Prostate cancer: the contribution of nuclear medicine.

PMID- 10961284
TI  - Scrotal ultrasonography: an update.

PMID- 10961285
TI  - Imaging in male hypofertility and impotence.

PMID- 10961286
TI  - Interventional uroradiology: an update.

PMID- 10961287
TI  - Interventional magnetic resonance imaging.

PMID- 10961288
TI  - News from around the world. Scotland.

PMID- 10961289
TI  - Report of the Food and Drug Administration Subcommittee on Xenotransplantation:
      meeting of 13 January 2000, Center for Biologics Evaluation and Research.

PMID- 10961290
TI  - Address by the Honorary Founding President of the Xenotransplantation Society.
      The eye of an eagle: xenobiology and the quest for bioadvantage.
AB  - My purpose in these remarks is to stimulate us to consider the vast array that
      nature has provided us in the differentiation of species, and to examine the
      possibility that some of these differences might prove useful in other species,
      including man.

PMID- 10961291
TI  - Natural antibodies and the host immune responses to xenografts.
AB  - Natural antibodies are present in the serum of individuals in the absence of
      known antigenic stimulation. These antibodies are primarily IgM, polyreactive,
      and encoded by immunoglobulin V genes in germline configuration. Natural
      antibodies are produced by B-1 lymphocytes, cells that form the primary cell of
      the fetal and newborn B cell repertoire and may represent the basic foundation
      upon which the adult repertoire of B cell antibodies is based. Natural antibodies
      react with a variety of endogenous and exogenous antigens, including xenoantigens
      expressed by tissues between unrelated species. These antibodies are capable of
      causing the immediate rejection of grafts exchanged across species barriers. One
      of the central issues related to our understanding of the immunopathologic
      mechanisms responsible for rejection of xenografts is whether pre-formed natural
      antibodies and new antibodies induced following xenotransplantation are produced
      by the same pathways of B cell antibody production. We have established in
      studies conducted in rodents and humans that the initial phases of antibody
      production xenogeneic tissues involves the use of a restricted population of Ig
      germline genes to encode xenoantibody binding. As the humoral xenoantibody
      response matures, the same closely-related groups of Ig V genes are used to
      encode antibody binding and there is evidence for an isotype switch to IgG
      antibody production and the appearance of somatic mutations consistent with
      antigen-driven affinity maturation. Our findings in both rodent and human studies
      form the basis for our proposal that the xenograft response reflects the use of B
      cell natural antibody repertoires originally intended to provide protection
      against infection. The host humoral response is inadvertently recruited to mount
      antibody responses against foreign grafts because they display carbohydrate
      antigens that are shared by common environmental microbes. This model of
      xenoantibody responses is being tested in our laboratory through the analysis of
      the binding of xenoantibodies in their original non-mutated configuration, and
      the examination of the effect of specific point mutations and gene shuffling have
      on xenoantibody binding activity. Establishment of the relationships between Ig
      structural changes and subsequent changes in binding affinity should provide
      important insights into the role that, natural antibodies and the cells that
      produce them play in the evolution of the host's humoral responses to xenografts.

PMID- 10961292
TI  - Xenotransplantation from swine: making a list, checking it twice...

PMID- 10961293
TI  - Growth of porcine kidneys in their native and xenograft environment.
AB  - The increased survival of hDAF pig-to-primate renal xenografts for up to two
      months has afforded the opportunity to study physiological aspects such as organ
      growth. Experimental evidence exists of species restriction of the activity of
      growth hormone, although growth itself is also controlled by a number of other
      endocrine, paracrine and autocrine substances. This study consisted of four
      parts: (1) measurement of pig kidney size according to pig body weight; (2)
      measurement of pig kidney size according to pig age; (3) serial length
      measurement of pig-to-primate renal xenografts; (4) correlation of terminal
      weight of renal xenograft with age and histology. The xenografted pig kidneys in
      a primate recipient grow as they would in the pig for the first two weeks after
      transplantation. After this time there is a reduction in the rate of increase in
      the length of the xenograft. Over the same period, changes in weight are greatly
      increased by the presence of rejection. This observational study supports the
      notion that regulation of growth of a xenotransplanted porcine kidney occurs.

PMID- 10961294
TI  - Comparative study of theefficacy of removal of anti-ABO and anti-gal antibodies
      by double filtration plasmapheresis.
AB  - Successful clinical ABO-incompatible renal transplantation has been achieved by
      the removal of anti-A or anti-B antibodies using double filtration plasmapheresis
      (DFPP). We have compared changes in the levels of anti-donor antibodies and the
      histopathology of the renal grafts following human ABO-incompatible
      allotransplantation and pig-to-baboon xenotransplantation using pretransplant
      DFPP. DFPP was performed on days 6, -4, -2 and -1 before the ABO-incompatible
      transplants (n=25) and on days -2 and 0 (immediately before reperfusion) in the
      xenotransplants (n=4). In two baboons (XenoTx Group I) the extent of antibody
      removal was comparable to that in the ABO-incompatible patients, and an even
      greater level of removal was achieved in another two baboons (XenoTx Group II).
      Anti-A and anti-B and anti-pig IgM and IgG antibodies were measured by flow
      cytometry. All clinical ABO-incompatible renal grafts are functioning, except two
      which were lost from recurrence of the original disease or from chronic
      rejection. Three other grafts underwent humoral rejection episodes, which were
      successfully treated. DFPP reduced the mean anti-A/B IgM and IgG antibody levels
      to 8% and 13% of pretreatment levels, respectively. After kidney transplantation,
      they were maintained at 37% and 46% of pre-DFPP level. No antibody binding to the
      transplanted kidney was detected at any time (1 h to 2 yr) after ABO-incompatible
      allotransplantation. In contrast, in XenoTx Group I, the same extent of antibody
      removal (90%) prevented hyperacute rejection, but the two grafts were rejected on
      days 6 and 7, respectively, from acute vascular rejection. In XenoTx Group II,
      the additional DFPP that was required to deplete the remaining 10% of anti-pig
      antibody was poorly tolerated and the two baboons died 4 h and 2 days,
      respectively, after renal transplantation. Although anti-pig IgM antibodies were
      reduced to 2% of pre-treatment level, IgM and C3 binding were detected in the
      graft as early as 1 h posttransplantation. These data suggest that the
      concentration of xeno-antigen epitopes expressed on pig organs may need to be
      reduced by genetic engineering to the much lower level of blood group A/B
      antigens on human kidneys if discordant xenotransplantation is to be successful.

PMID- 10961295
TI  - Human and non-human primate anti-galactosyl response after injection of rat
      monoclonal antibody bearing galactosyl epitopes.
AB  - In the case of clinical use of pig-to-human xenografting, any exogenous source of
      to-galactosyl epitopes will elicit an anti-galactosyl immune response, which
      could be deleterious for the xenograft. The presence of Galalpha(1-3)Gal residues
      was thus examined by western blotting on various rat monoclonal antibodies (mAb),
      which are used in clinical trials. In parallel, the anti-galactosyl humoral
      response was assessed in the serum of kidney allograft recipients and
      experimental baboons, which received these mAbs. Galactosyl residues were
      evidenced on all rat monoclonal antibody tested. The anti-galactosyl response was
      weak in kidney allograft recipients receiving a basic immunosuppression
      (Cyclosporine, Azathioprine, Prednisolone) and iterative injections of rat mAbs.
      In contrast, untreated or immunosuppressed baboons that received rat mAbs
      developed a major anti-galactosyl humoral response. These results suggest that
      anti-galactosyl sensitization produced by therapeutic agents will have to be
      considered in the case of clinical xenotransplantation.

PMID- 10961296
TI  - Concordant xenotransplantation--non-vascularized pancreatic islets are more
      difficult to regraft than the vascularized heart.
AB  - We have previously demonstrated that it is possible to perform retransplantation
      of a xenogeneic heart (mouse-to-rat) using cyclosporine A as monotherapy,
      provided that the first heart is transplanted under a short course of
      deoxyspergualin (DSG). If DSG is omitted, the first heart is rejected within four
      days and the second heart succumbs to hyperacute rejection within minutes. A
      mouse heart as first graft does not protect a consecutive pancreatic islet graft,
      although the heart continues to function after rejection of the cellular graft.
      One explanation for this discrepancy may be the fact that cellular grafts, as
      pancreatic islets, lack an endothelial lining. We have, therefore, further
      investigated possible differences between vascularized and non-vascularized
      xenografts regarding their capacity to induce unresponsiveness. The use of
      pancreatic islets as primary graft neither accelerated nor decelerated the speed
      of rejection of the vascularized heart used as secondary graft. Furthermore,
      hemagglutinating and cytotoxic antibody titres responded in the same manner as in
      naive rats transplanted with a mouse heart. Retransplantation with pancreatic
      islets also resulted in complete rejection of both the primary and secondary
      grafts. Thus, the lack of unresponsiveness cannot simply be explained by
      differences, between the pancreatic and cardiac tissues, in antigen expression.
      In addition, intraperitoneal transplantation of mouse heart cells as primary
      graft resulted in rejection of a secondary cardiac graft after three days.
      However, it cannot be totally excluded that the time of antigen exposure had an
      impact on these results. In conclusion, our previous and present studies suggest
      that the presence of an intact vascular bed, both in the first and second graft,
      is necessary to create a state of unresponsiveness. Because the pancreatic islets
      lack an endothelial lining, they do not benefit from an unresponsiveness of the
      immune system. Neither are they able to induce such an unresponsiveness.

PMID- 10961297
TI  - The critical role of mouse CD4+ cells in the rejection of highly disparate
      xenogeneic pig thymus grafts.
AB  - Long-term survival of fetal pig thymus (FP THY) grafts and efficient repopulation
      of mouse CD4+ T cells is achieved in thymectomized (ATX) B6 mice that receive T
      and NK cell depletion by injection of a cocktail of mAbs (GK1.5, 2.43, 30-H12,
      and PK136) and fetal pig thymus/liver (FP THY/LIV) grafts. The requirement for
      each mAb in this conditioning regimen in order to avoid the rejection of FP THY
      grafts has not yet been defined. In our present studies, CD4 cell-depleted ATX B6
      mice and euthymic MHC class II-deficient (IIKO) mice were employed to investigate
      the role of mouse CD4+ cells in the rejection of FP THY grafts in vivo. After
      grafting FP THY/LIV to CD4+ cell-depleted ATX B6 mice, efficient repopulation of
      mouse CD4+ T cells was observed in the periphery. However, only two of four mice
      had remaining FP THY grafts by 17 weeks post-implantation, and these were of poor
      quality, whereas four of four T and NK cell-depleted ATX B6 mice had well
      developed FP THY grafts. Furthermore, three of four FP THY/LIV-grafted, CD4+ cell
      depleted ATX B6 mice rejected donor MHC-matched pig skin grafts. In contrast,
      three of three FP THY/LIV grafted, T and NK cell-depleted, ATX B6 mice accepted
      donor MHC-matched pig skin grafts, suggesting that optimal tolerance to
      xenogeneic pig antigens was not achieved in mice conditioned only with anti-CD4
      mAb. ATX B6 mice treated with only anti-CD8 mAb rejected FP THY completely by 6
      weeks post-grafting, a time when CD4+ cell-depleted ATX B6 mice had well
      vascularized FP THY grafts. In addition, when euthymic IIKO mice were pre-treated
      with the standard conditioning regimen that includes four different mAbs, FP THY
      grafts survived and supported the repopulation of mouse CD4+ T cells in the
      periphery, while high levels of mouse CD8+ T cells developed in host thymi. These
      studies suggest that mouse CD4+ T cells play a critical role in the acute
      rejection of xenogeneic FP THY grafts. Without help from CD4+ cells, mouse CD8+
      cells, NK, NK/T, and TCR(gamma/delta)+ T cells do not mediate acute rejection of
      FP THY grafts. Furthermore, our results suggest that other cell subsets besides
      CD4+ T cells play a role in the delayed rejection of highly disparate xenogeneic
      FP THY grafts.

PMID- 10961298
TI  - Productive infection of primary human endothelial cells by pig endogenous
      retrovirus (PERV).
AB  - The potential risk of viral transmission in the setting of xenotransplantation
      has gained major attention. Different porcine cell types have been shown to
      release retroviral particles, which are infectious for human cell lines in vitro.
      However, there are only a few data on whether PERV (pig endogenous retrovirus) is
      able to infect primary human cells. In this study we have analyzed endothelial
      cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic
      stem cells and bone marrow stromal cells for PERV transmission. We now provide
      evidence for primary human endothelial cells, vascular fibroblasts, and mesangial
      cells to be susceptible to PERV transmission. PERV infection was productive in
      endothelial cells and mesangial cells. Our data confirm and extend former reports
      concerning the PERV infection of human cells. The PERV infection of different
      primary human cells represents further significant evidence for a viral risk
      during xenotransplantation. In this context, special attention should be directed
      towards productive infection of human endothelial cells: in the setting of
      xenotransplantation this cell type will have close contact with porcine cells and
      PERV particles.

PMID- 10961299
TI  - An approach to the control of disease transmission in pig-to-human
      xenotransplantation.
AB  - Although several major immunologic hurdles need to be overcome, the pig is
      currently considered the most likely source animal of cells, tissues and organs
      for transplantation into humans. Concerns have been raised with regard to the
      potential for the transfer of infectious agents with the transplanted organ to
      the human recipient. This risk is perceived to be increased as it is likely that
      the patient will be iatrogenically immunocompromised and the organ-source pig may
      be genetically engineered in such a way to render its organs particularly
      susceptible to infection with human viruses. Furthermore, the risk may not be
      restricted to the recipient, but may have consequences for the health of others
      in the community. The identification of porcine endogenous retroviruses and of
      hitherto unknown viruses have given rise to the most concern. We document here
      the agents we believe should be excluded from the organ-source pigs. We discuss
      the likelihood of achieving this aim and outline the potential means by which it
      may best be achieved.

PMID- 10961300
TI  - Literature update 1999, part 3. Xenotransplantation.

PMID- 10961301
TI  - Design of the monolithic polymers used in capillary electrochromatography
      columns.
AB  - Monolithic columns for capillary electrochromatography (CEC) are receiving quite
      remarkable attention. Both the simplicity of the in situ preparation and the
      large number of readily available chemistries make the monolithic separation
      media a vital alternative to capillary columns packed with particulate materials.
      This review summarizes the current state-of-the-art in this rapidly growing area
      of CEC with a focus on monolithic capillary columns prepared from synthetic
      polymers. Recent achievements in column technologies for both high-performance
      liquid chromatography and capillary electrophoresis are used as the starting
      point to highlight the influence of these well established analytical methods on
      the development of monolithic capillary columns for CEC. The effects of
      individual variables on the separation properties of monolithic capillaries are
      discussed in detail. The analytical potential of these columns is demonstrated
      with separations involving various families of compounds in different
      chromatographic modes.

PMID- 10961302
TI  - Open tubular capillary electrokinetic chromatography in etched fused-silica
      tubes.
AB  - This review describes an open tubular approach to capillary electrochromatography
      (OTCEC) that first etches the inner surface of the fused-silica tube using
      ammonium hydrogen diflouride. This process can increase the inner surface area
      significantly. The new surface is then chemically modified to attach a bonded
      stationary phase using a silanization/hydrosilation reaction process. The
      surfaces are characterized spectroscopically by diffuse reflectance infrared
      Fourier transform and by electroosmotic flow measurements. Applications of OTCEC
      columns with C18, diol and chiral stationary phases are described.

PMID- 10961303
TI  - Packing columns for capillary electrochromatography.
AB  - Considering the current interest in capillary electrochromatography (CEC),
      performed in packed columns, we present the different methods used to pack
      capillary columns for use in CEC. General considerations on column packing are
      given and the column fabrication process is discussed in sufficient detail to
      allow instruction to those who are not experienced in the field. Five different
      packing methods are discussed to deliver packing material into the capillary
      column from a practical view point: slurry pressure packing, packing with
      supercritical CO2, electrokinetic packing, using centripetal forces, and packing
      by gravity. Entrapment of particulate material by sintering and sol-gel
      technology is also mentioned. Although slurry pressure packing procedures are
      most common, higher separation efficiencies are obtained using other packing
      approaches. Electrokinetic packing seems to be the simplest technique to deliver
      the packing material into the capillary columns. Nevertheless, as with the other
      packing techniques, skill and experience are required to complete all the steps
      involved in the fabrication of packed columns for CEC.

PMID- 10961304
TI  - Instrumentation for capillary electrochromatography.
AB  - One of the reasons for the immense interest in capillary electrochromatography
      (CEC) is its feature to combine chromatographic selectivity with the high
      efficiency and the miniaturization potential of capillary electrophoresis (CE).
      The capability of commercial CE instruments to run CEC has enforced the readiness
      of users and researchers to work on this separation technique. Nevertheless, to
      fully exploit the potential of CEC, a routine CE device can certainly not fulfill
      all requirements. Two different approaches have been made to overcome this
      problem. The first was to modify commercial CE instruments for various demands.
      Pressurization of the packed capillary to prevent "air" bubble formation,
      gradient elution capabilities and thermostating devices allowing a greater
      flexibility in column designs have been implemented in CE instruments of several
      manufacturers. A completely different approach is the development of modular
      laboratory-made instrumentation dedicated to special CEC requirements. In order
      to increase mobile phase velocity and thus the speed of analysis the availability
      of voltages higher than 30 kV was accomplished in some of these devices. Gradient
      elution was achieved by either coupling of gradient LC systems or an
      electroosmotic generation of the changing eluent composition. When a pressure
      gradient is applied between both column ends in addition to the voltage gradient,
      a hybrid between capillary HPLC and CEC results. This chromatographic mode is
      named pressure-assisted electrochromatography (PEC). Either CE instruments
      equipped with additional HPLC pumps or modular laboratory-made devices are
      suitable for PEC. In CEC, sensitivity for UV detection is rather poor due to the
      short optical path length for on-column detection in capillary separation
      techniques. A special cell design with enhanced light path is presented and
      further principles like, e.g., fluorescence detection and coupling to mass
      spectrometry are discussed.

PMID- 10961305
TI  - Use of on-line mass spectrometric detection in capillary electrochromatography.
AB  - Capillary electrochromatography (CEC) is a liquid phase analytical separation
      technique that is generally carried out with packed capillary columns by
      electroosmotically driven mobile phase at high electric field strength. The
      analytes are separated by virtue of the differences in their distribution between
      the mobile and stationary phases and, if charged in their electrophoretic
      mobilities as well. It is thus considered a hybrid of liquid chromatography and
      capillary electrophoresis and is expected to combine the high peak efficiency of
      capillary zone electrophoresis (CZE) with the versatility and loading capacity of
      HPLC. This review explores the potential use of on-line mass spectrometric
      detection for CEC. It discusses key design issues that focus on the physical and
      electrical arrangement of the CEC column with respect to the electrospray orifice
      inlet. The salient features of the sheathless, sheath flow and liquid junction
      interfaces that are frequently employed while coupling a CEC column to an
      electrospray ionization mass spectrometry system are also highlighted. Possible
      configurations of the CEC column outlet that would obviate the need for
      pressurizing the capillary column are also presented. While coupling CEC with MS
      both the nature of the interface and the configuration of the column outlet will
      determine the optimal arrangement. The review also discusses bandspreading that
      occurs when a connecting tube is employed to transfer mobile phase from the
      column outlet to the atmospheric region of the electrospray source with a
      concomitant loss in sensitivity. Selected examples that highlight the potential
      of this technique for a wide range of applications are also presented.

PMID- 10961306
TI  - Capillary electrochromatography-mass spectrometry for the separation and
      identification of isomeric polyaromatic hydrocarbon DNA adducts derived from in
      vitro reactions.
AB  - Capillary electrochromatography (CEC) is an emerging technique that combines
      features of both micro-capillary high-performance liquid chromatography
      (microHPLC) and capillary electrophoresis (CE). This separation technique
      possesses high speed and the efficiency of an electro-driven system, while the
      selectivity and sample loadability compare to those of a packed capillary LC
      column. Since the separation mechanism is based on that of HPLC, the concept of
      isoeluotropic strength and selectivity of solvents as well as the on-column
      focusing techniques for sample introduction used in LC can be applied in CEC.
      This article examines some of these features of CEC in the context of our own
      experiences with the technique. More specifically, emphasis is placed on
      applications of CEC to the analysis of DNA adducts of polyaromatic hydrocarbons
      by coupling CEC to mass spectrometry. It is shown that, with proper selection of
      mixed organic modifiers in the mobile phase, i.e. ternary and quaternary mobile
      phases, complex DNA adduct mixtures derived from in vitro reactions can be
      separated isocratically with improved selectivity and much greater speed than by
      HPLC. Additionally, the speed of the analysis is further enhanced by employing a
      step gradient. Furthermore, CEC may be easily coupled to mass spectrometry such
      that the characterization of each isolated component from the mixtures is
      performed on-line with the separation. By using on-column focusing, the sample
      loadability onto a CEC column is improved.

PMID- 10961307
TI  - Gradient elution techniques for capillary electrochromatography.
AB  - Capillary electrochromatography (CEC) is a rapidly maturing technique, but still
      in need of further instrumental development and in need of unique applications
      that are not possible by traditional pressure-driven LC. We review the
      development of gradient elution schemes for CEC, beginning with pH gradients
      initially developed for capillary electrophoresis. Step gradients are the most
      easily instrumentally implemented, but provide less flexibility in separation
      than continuous gradients. Pressure-assisted CEC is easily adapted to gradient
      elution schemes, but does not offer the advantages of very high column efficiency
      provided by totally electro-driven mobile phases. The development of flow
      injection interfaces allows a true solvent gradient to be generated by micro-LC
      pumps, with the mobile phase drawn into the separation capillary by pure
      electroosmotic flow. While requiring both a CEC instrument and a traditional pump
      or pumps capable of generating the gradient, this method offers advantages of
      greatly reduced column handling, prolonging column lifetimes, and allows simple
      autosampling. We also discuss voltage gradients, which provide a mobile phase
      velocity gradient.

PMID- 10961308
TI  - Highly selective separations by capillary electrochromatography: molecular
      imprint polymer sorbents.
AB  - Molecular imprint polymers (MIPs) are synthesized in the presence of a template,
      or 'imprint' molecule which results in the formation of specific recognition
      cavities complementary to the template in shape and chemical functionality. The
      resultant MIP then acts as a selective binding medium for the template molecule.
      The utility of MIPs lies in the selectivity of the rebinding process, which is
      based on molecular recognition. In many cases, the selectivity achieved with MIPs
      toward a particular molecule is comparable to that observed with antibodies. This
      has led to the application of MIPs to several areas of analytical chemistry
      including immunoassays, sensors and separations media. One of the most successful
      application areas of MIPs has been as chromatographic sorbents, where they have
      been utilized predominately in chiral separations. The use of MIP sorbents in CEC
      is attractive in that it combines the selectivity of a molecular recognition
      process with the enhanced flow dynamics of CEC, which can result in higher
      efficiency and shorter analysis times. This paper will review the use of
      molecular imprinted stationary phases in CEC. Following a brief introduction to
      molecular imprinting, various methodologies for preparation of MIP-CEC
      capillaries in addition to applications of the technique will be discussed.

PMID- 10961309
TI  - Specific applications of capillary electrochromatography to biopolymers,
      including proteins, nucleic acids, peptide mapping, antibodies, and so forth.
AB  - Separation of biopolymers is an obvious application of capillary
      electrochromatography (CEC) technology, since speed and resolution should
      increase significantly over high-performance liquid chromatography (HPLC). All
      too often, HPLC chromatograms of polymers show poorly resolved envelopes of
      overlapping peaks from oligomers. The practical limitation of column length and
      pressure drop has hindered development of high resolution separations of many
      polymers in HPLC. However, this generally applies only to packed beds of small
      particles, and not to continuous (or monolithic) beds, as introduced by Hjerten
      et al. [S. Hjerten, Ind. Eng. Chem. Res. 38 (1999) 1205; S. Hjerten, C. Ericson,
      Y.-M. Li, R. Zhang, Biomed. Chromatogr. 12 (1998) 120; C. Ericson, S. Hjerten,
      Anal. Chem. 71 (1999) 1621; J.-L. Liao, N. Chen, C. Ericson, S. Hjerten, Anal.
      Chem. 68 (1996) 3468; S. Hjerten, A. Vegvari, T. Srichaiyo, H.-X. Zhang, C.
      Ericson, D. Eaker, J. Capillary. Elec. 5 (1998) 13; C. Ericson, J.-L. Liao, K.
      Nakazato, S. Hjerten, J. Chromatogr. A 767 (1997) 33; S. Hjerten, D. Eaker, K.
      Elenbring, C. Ericson, K. Kubo, J.-L. Liao, C.-M. Zeng, P.-A. Lidstrom, C. Lindh,
      A. Palm, T. Srichiayo, L. Valtcheva, R. Zhang, Jpn. J. Electroph. 39 (1995) 1].
      Throughout this review we will refer to such packings as monolithic or continuous
      beds, but they are identical type packings, formed by the in situ polymerization
      in the capillary or column. CEC capillaries can be much longer, and contain
      smaller particles than is practical for HPLC. This improves resolution
      significantly. CEC is able to capitalize on existing mobile phase technology
      developed over 30 years to improve separations. The requirement that the mobile
      phase simultaneously promote the separation and mobile phase mobility needs to be
      considered. In RPLC, this dual role is not much of a problem. It may be much more
      important in other modes, particularly ion-exchange (IEC). As the field develops,
      it is becoming clear that CEC is not just a simple extension of HPLC.
      Instruments, column technology and operating optima are clearly different than
      HPLC. CEC will develop into its own unique field. Open tubular HPLC is almost
      precluded by the high pressures required for forcing liquids through 10 microm or
      smaller capillaries. Electroosmotic pumping (EOF) avoids the pressure constraints
      and provides better flow profiles. Compared to HPCE, the ability to interact with
      the stationary phase may enable separations that would be difficult with
      electrophoresis alone. Since the mobile phase can be less complex than micellar
      electrokinetic chromatography (MEKC), CEC also avoids the problem of high
      background signals from the micelle forming compounds. Thus CEC-MS (mass
      spectrometry) is expected to be even more powerful than HPCE-MS. The fortuitous,
      simultaneous development of matrix assisted laser desorption-time of flight MS
      (MALDI-TOF-MS) technology will enable extension of the mass range to above 100
      000 Da. Lack of familiarity is the perhaps the largest liability of CEC compared
      to other techniques. This paper critically compares the state-of-the-art of CEC
      with HPLC and HPCE, with a particular emphasis on separation of biopolymers. The
      goal is to help the reader overcome the fear of the unknown, in this case, CEC.

PMID- 10961310
TI  - Capillary electroendoosmotic chromatography of peptides.
AB  - This review focuses on the current state of peptide separation by capillary
      electroendoosmotic chromatography (CEC). When carried out under optimised
      conditions, peptide separation by CEC methods represents an orthogonal and
      complementary technique to micro-HPLC (micro-HPLC) and high-performance capillary
      zone electrophoresis (HPCZE). The origin of the selectivity differences that can
      be achieved with these three separation techniques (CEC, micro-HPLC and HPCZE),
      respectively are discussed, and the current limits of performance with CEC
      methods documented. Peptide separations by CEC methods with n-alkyl bonded
      silicas or mixed-mode phases are also illustrated. The development of different
      variants of CEC and pressurised CEC (also commonly referred to in the literature
      as electrically-assisted micro-HPLC) are examined. The potential of coupling CEC
      systems to mass spectrometers for real-time analyses of peptides or protein
      digests has been examined. Several future directions for the application of this
      technique in phenotype/proteomic and zeomic mapping of naturally occurring
      peptides and proteins are highlighted.

PMID- 10961311
TI  - Theory for migration of ions in capillary electrochromatography.
AB  - The fundamental migration theories for chromatography and electrophoresis are
      both based on a solution of the mass balance equation. The corresponding analysis
      for an electrochromatographic system has previously been published and is
      analysed in more detail in this paper. It is shown that the resulting equation,
      Eq. (8) in this paper, is in agreement with both electrophoretic and
      chromatographic theories and that when these migration modes are mixed a
      complicated migration behaviour emerge. These complications arise, if the
      comparison is done with electrophoretic theory, because the presence of the
      stationary phase creates a number of new restrictions on the system
      (electroneutrality on the stationary phase and simultaneous equilibrium for all
      components between the eluent and stationary phase). From a mathematical point of
      view, these restrictions make it difficult for the system to satisfy the
      coherence condition and this in turn may lead to an anomalous behaviour. To
      minimise the possibility for a complicated behaviour it is advisable to avoid too
      much mixing of the two migration mechanisms and/or to match the mobilities of the
      ionic components in the eluent phase with the mobility of the analyte ion.

PMID- 10961313
TI  - Separation of basic solutes by reversed-phase capillary electrochromatography.
AB  - The separation of basic solutes at low pH by capillary electrochromatography
      (CEC) has been investigated. The feasibility of separation of basic solutes by
      CEC was demonstrated. Influence of operational parameters, solvent composition,
      pH, temperature on retention and selectivity of the separation of a mixture of
      basic, neutral and acidic drug standards has been investigated. The observed
      elution behavior has been modeled to account for both chromatographic retention
      and differential electrophoretic mobility of the solutes. This model was verified
      experimentally. It is demonstrated in this work that the elution window of
      solutes in reversed-phase CEC is expanded to range from -1 to infinity.

PMID- 10961312
TI  - Modelling of the pore flow in capillary electrochromatography.
AB  - Pore flow in capillary electrochromatography (CEC) on porous silica particles has
      been investigated. To that end the migration behaviour of narrow polystyrene (PS)
      standards dissolved in di-methylformamide (DMF) with lithium chloride in 1 and 10
      mmol/l concentration has been measured. These data have been compared to
      theoretical predictions. The latter were based on a model comprising cylindrical
      pores of varying diameter as measured experimentally by porosimetry, while the
      flow in each set of pores was calculated with the expression given by Rice and
      Whitehead. A reasonable to good agreement between experimental and predicted data
      was observed, provided it was assumed that pores of differing diameter occur in
      series. It was found that the flow in pores with a nominal size of 100 A can be
      considerable compared to the interstitial flow, especially at 10 mmol/l ionic
      strength. It is concluded that pore flow within porous particles in CEC, of great
      importance for improved efficiency in both interactive and exclusion type CEC,
      can be predicted fairly reliably by means of the Rice and Whitehead expression.

PMID- 10961314
TI  - Separation of acidic compounds by strong anion-exchange capillary
      electrochromatography.
AB  - Separation of the acidic compounds in the ion-exchange capillary
      electrochromatography (IE-CEC) with strong anion-exchange packing as the
      stationary phase was studied. It was observed that the electroosmotic flow (EOF)
      in strong anion-exchange CEC moderately changed with increase of the eluent ionic
      strength and decrease of the eluent pH, but the acetonitrile concentration in the
      eluent had almost no effect on the EOF. The EOF in strong anion-exchange CEC with
      eluent of low pH value was much larger than that in RP-CEC with Spherisorb-ODS as
      the stationary phase. The retention of acidic compounds on the strong anion
      exchange packing was relatively weak due to only partial ionization of them, and
      both chromatographic and electrophoretic processes contributed to separation. It
      was observed that the retention values of acidic compounds decreased with the
      increase of phosphate buffer and acetonitrile concentration in the eluent as well
      as the decrease of the applied voltage, and even the acidic compounds could elute
      before the void time. These factors also made an important contribution to the
      separation selectivity for tested acidic compounds, which could be separated
      rapidly with high column efficiency of more than 220000 plates/m under the
      optimized separation conditions.

PMID- 10961315
TI  - Comparison of aqueous and non-aqueous capillary electrochromatography for the
      separation of basic solutes.
AB  - The analysis of basic compounds by capillary electrochromatography (CEC) on
      silica-based materials using conventional HPLC stationary phases has failed to
      address the problem of severe peak tailing and non-reproducible chromatography.
      Several new generation stationary phases were evaluated using aqueous and non
      aqueous mobile phases. The best results were obtained in the aqueous mode using
      Waters Symmetry Shield RP-8, a material in which the residual silanol groups were
      shielded by an octylcarbamate function. For comparison, experiments were carried
      out using unmodified silica.

PMID- 10961316
TI  - High temperature and temperature programming in capillary electrochromatography.
AB  - In electrochromatography, solvent electrophoretic mobility and solute
      partitioning are temperature dependent processes. If temperature variations are
      controlled, solute selectivity and analysis times can be tailored. In this study
      the feasibility of temperature programming in capillary electrochromatography
      (CEC) was demonstrated using a reversed-phase CEC mode. The outcome of programmed
      separations was compared with isothermal, isocratic and isorheic (constant flow)
      separations. The combined effects of column temperature and mobile phase flow
      rate changes during the separation run, resulted in up to a 50% reduction in the
      separation run time, without adversely affecting the quality of separation. For
      capillary electrochromatography, temperature programming may be a valuable
      alternative to solvent programming modes because of the great technical
      difficulties associated with carrying out solvent gradient elution.

PMID- 10961317
TI  - Preparation of stationary phases for open-tubular capillary electrochromatography
      using the sol-gel method.
AB  - Capillary electrochromatography requires the deposition of a stationary phase
      inside the capillary. In this paper the sol-gel method is proposed for this
      purpose. The gels were prepared externally and injected into a fused-silica
      capillary, where anchorage to the capillary wall was possible through
      condensation reactions between the silanol groups of the capillary wall and the
      residual silanol groups the gel. Contrary to a commonly used practice, alkaline
      pretreatment of the inner capillary wall prior to the introduction and anchoring
      of the gel was found to be only marginally effective in improving the mechanical
      stability of the column. The influence of various parameters, such as the pH, the
      water content, the presence of alcohol (ethanol) on the formation of
      tetraethoxysilane (TEOS)-n-octyltriethoxysilane (C8-TEOS) hybrid gels of varied
      composition is discussed. The pH and the amount of water present were found to be
      the determining factors in the preparation of a stable gel with the desired
      mechanical and chromatographic properties. By carrying out the gel formation at
      80 degrees C, capillary columns could be produced in 2.5 h. While an acidic pH
      was required during (external) gel formation, subsequent treatment of the gel
      inside the capillary with an alkaline solution ('aging') was found to improve
      separation and stationary phase capacity significantly. The capillary columns
      were subsequently used to separate a mixture of polycyclic aromatic hydrocarbons
      in less than 3 min.

PMID- 10961318
TI  - Capillary electrochromatography using continuous-bed columns of sol-gel bonded
      silica particles with mixed-mode octadecyl and propylsulfonic acid functional
      groups.
AB  - Continuous-bed columns containing sol-gel bonded 3 microm silica particles with
      mixed-mode octadecyl and propylsulfonic acid functional groups (ODS/SCX) were
      prepared by first packing the ODS/SCX particles into a fused-silica capillary,
      then filling the packed capillary with a siliceous sol-gel, curing the sol-gel,
      and finally drying the column with supercritical carbon dioxide. The performance
      of the sol-gel bonded ODS/SCX columns was evaluated for capillary
      electrochromatography using acetonitrile aqueous mobile phase containing
      phosphate buffer. The columns were mechanically strong and permeable. Both EOF
      velocity and current increased linearly with elevation of the applied electric
      field strength. The EOF velocity was high at low pH and nearly constant over a
      range of pH 2-9. Higher buffer concentration resulted in higher current and lower
      EOF velocity. The acetonitrile content had no significant effect on the EOF.
      Without thermosetting the column, no bubble formation was noticed with currents
      up to 2.5 microA. The minimum plate height of a 25/34 cm x 75 microm I.D. sol-gel
      bonded 3 microm ODS/SCX column was 5.7 microm (1.75 x 10(5) plates per meter) at
      an optimum EOF velocity of 0.92 mm s(-1). Mixtures of test aromatic compounds and
      aromatic hydrocarbon homologues gave symmetrical peaks when using a low pH mobile
      phase. The retention and elution order of aromatic compounds represented a
      typical reversed-phase separation mechanism similar to conventional ODS columns.
      The run-to-run and column-to-column retention factor reproducibility was better
      than 2.5% and 8.0% RSD, respectively.

PMID- 10961319
TI  - Characteristics of particle-loaded monolithic sol-gel columns for capillary
      electrochromatography. I. Structural, electrical and band-broadening properties.
AB  - Particle-loaded (3 microm, C18) monolithic sol-gel columns have been prepared and
      selected characteristics measured. They have a surprisingly high permeability,
      allowing their operation in the microLC mode at pressures as low as 69 kPa where
      their efficiency is about 50000 plates per meter and the CEC mode where
      efficiency is at least 106000 plates per meter. These columns can withstand over
      13.8 MPa pressure without compression or movement within the 75 microm capillary.
      Field strengths in the packed segments are approximately 50% greater than those
      in the open segments, due to the higher resistivity of the particle-laden
      regions. There is a relatively rapid loss of efficiency with increasing linear
      velocity in both the CEC and microLC modes, which may be due to a tortuosity
      effect in the inter- and intra-particulate voids. Chromatographic behavior is
      characteristic of conventional C18 particles, indicating that analytes have
      significant access to the surface within the pores of the immobilized bonded
      phase.

PMID- 10961320
TI  - Capillary electrochromatography with novel stationary phases. IV. Retention
      behavior of glycosphingolipids on porous and non-porous octadecyl sulfonated
      silica.
AB  - In this investigation, capillary electrochromatography (CEC) with a novel
      stationary phase proved useful for the separation of neutral and acidic
      glycosphingolipids (GSLs). Four different gangliosides, namely G(M1a), G(D1a),
      G(D1b) and G(T1b), served as the acidic GSLs model solutes. The following four
      GSLs: galactosylceramide (GalCer), lactosylceramide (LacCer),
      globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) served as the
      typical neutral GSLs. The stationary phase, octadecyl sulfonated silica (ODSS),
      consisted of octadecyl functions bonded to a negatively charged layer containing
      sulfonic acid groups. Porous and non-porous ODSS stationary phases were examined.
      The retention behavior of the acidic and neutral GSLs was examined over a wide
      range of elution conditions, including the nature of the electrolyte and organic
      modifier and the pH of the mobile phase. The porous ODSS stationary phase yielded
      the separation of the four different gangliosides using a hydro-organic eluent of
      moderate eluent strength whereas the non-porous ODSS stationary phase permitted
      the separation of the four neutral GSLs with a mobile phase of relatively high
      eluent strength.

PMID- 10961321
TI  - Stationary phase structures enhancing electroosmotic flow in capillary
      electrochromatography.
AB  - Several chemically bonded silicas with C18 groups were examined with respect to
      electroosmotic flow (EOF) velocities under CEC conditions. Stationary phases with
      low hydrophobic selectivity generally provided high EOFs. The stationary phases
      prepared by using octadecyltrichlorosilane showed greater EOF than those from
      octadecyldimethylchlorosilane. Restricted-access reversed-phase (RARP) packing
      materials having C18 groups inside the pores and silanols on the external
      surfaces showed higher EOF than monomeric C18 phases with similarly high
      hydrophobic selectivity. The RARP-type structure having silanols at the external
      surface seems to be effective for increasing EOF while maintaining the
      hydrophobic character of the solute binding sites.

PMID- 10961322
TI  - Comparison of different packing methods for capillary electrochromatography
      columns.
AB  - A study was carried out in which 50 microm I.D. fused-silica capillaries were
      packed with 3 microm octadecylsilane bonded silica, from the same batch, by four
      methods; liquid slurry and carbon dioxide supercritical carrier, each with and
      without the use of an ultrasonic probe. A neutral test mixture was analysed by
      capillary column in reversed-phase mode, and the reproducibility of the
      electroosmotic flow and of migration time, column efficiency and retention
      factors, was determined. Initially results suggested that there was no
      significant difference between properties of columns packed by different methods,
      and a more thorough statistical evaluation confirmed this; differences observed
      in the column performance were attributed to random variations between replicate
      columns, and not between packing methods. However, the variation was least when
      applying the ultrasonication during liquid slurry.

PMID- 10961324
TI  - Towards the column bed stabilization of columns in capillary electroendosmotic
      chromatography. Immobilization of microparticulate silica columns to a continuous
      bed.
AB  - This article discusses a novel method generating a continuous bed inside the CEC
      column. The column bed composed of microparticulate reversed-phase silica is
      completely immobilized by a hydrothermal treatment using water for the
      immobilization process. This process eliminates the manufacture of frits of both
      ends of the column and all problems associated with their preparation.
      Fundamental studies on operational parameters will be presented such as the
      dependence of the immobilization on the column temperature, the type of
      stationary phase and the column back pressure. The immobilized CEC columns show
      the same high column efficiency as packed columns with frits.

PMID- 10961323
TI  - Stationary phases for capillary electrochromatography.
AB  - This review summarizes the variety of stationary phases that have been employed
      for capillary electrochromatography (CEC) separations. Currently, about 70% of
      reported CEC research utilizes C18 stationary phases designed for liquid
      chromatography, but an increasing number of new materials (e.g., ion-exchange
      phases, sol-gel approaches, organic polymer continuous beds) are under
      development for use in CEC. Novel aspects of these different materials are
      discussed including the ability to promote electroosmotic flow, phase selectivity
      and activity for basic solutes. In addition, new column designs (polymer
      continuous beds and silica-sol-gel monoliths) are described.

PMID- 10961325
TI  - Towards the ultimate minimum particle diameter of silica packings in capillary
      electrochromatography.
AB  - Porous silica beads with an average particle diameter between 0.2 and 3 microm
      have been applied as packing material in capillary electrochromatography (CEC).
      The experiments were directed to investigate whether it is really feasible and as
      promising as expected to use such small particles. In CEC, plate heights of H
      approximately/= 1-2 d(p) can be achieved which is smaller than the plate heights
      usually attained in high-performance liquid chromatography. Using a capillary
      packed with 0.5 microm silica beads we achieved a plate height of H = 3 d(p)
      indicating the presence of dispersive effects like Joule heating. Calculations
      demonstrate that at a field strength of about 800 V cm(-1) one third of the plate
      height can be lost by Joule heating effects if the heat is not removed by a
      cooling system. Additionally, the H(u) curve is still descending at the maximum
      electroosmotic flow (EOF) velocity we generated with the modified capillary
      electrophoresis instrument. To fully exploit the potential of submicron size
      silicas higher field strengths, i.e., higher EOF velocities, must be attained. To
      study the influence of the kind of packing on the EOF porous as well as nonporous
      silicas have been applied. The experiments clearly indicate that the EOF of
      porous and nonporous silicas is the same. Since the EOF is more or less
      exclusively generated by the packing material the zeta potential of n-octyl
      bonded 0.5 microm silica has been determined. The dependence of the zeta
      potential on the pH is identical to the dependence of the EOF on the pH in a
      packed capillary. The point of zero charge of the silica is at pH 2-3.

PMID- 10961326
TI  - Aspects of column fabrication for packed capillary electrochromatography.
AB  - Various parameters have been evaluated to develop a process for optimization of
      column manufacture for packed capillary electrochromatography (CEC). Spherisorb
      ODS-1 was packed into 75 microm I.D. capillaries to establish a standard set of
      packing conditions to afford high-performance columns free of voids. Numerous
      silica-based packing materials including porous and non-porous reversed-phase and
      ion-exchange phases were employed to evaluate the applicability of the standard
      conditions. Success of column manufacture and performance demonstrate a
      relationship to the colligative properties of the packing materials under the
      applied conditions. Frequently encountered difficulties arising from inadequate
      column conditioning and void formation in the packed bed are identified and
      discussed.

PMID- 10961327
TI  - Improved column preparation and performance in capillary electrochromatography.
AB  - Problems encountered in capillary electrochromatography, i.e. non-reproducible
      column manufacture, bubble formation during usage, short column lifetimes and
      limited choice of packing particles are addressed by the development of fritless
      or single-frit, internally tapered, segmented and dead-volume free coupled
      capillary columns. The Van Deemter plots measured demonstrate the performance of
      these high-quality capillaries which are suitable for capillary
      electrochromatography as well as for capillary high-performance liquid
      chromatographic applications.

PMID- 10961328
TI  - Steroid profiles determined by capillary electrochromatography, laser-induced
      fluorescence detection and electrospray-mass spectrometry.
AB  - Macroporous, monolithic capillary electrochromatography (CEC) columns, featuring
      a hydrophobic stationary phase, have been applied to the separations of steroids
      with good column efficiency. Using isocratic and gradient elution runs, mixtures
      of neutral or conjugated steroids could be resolved. While dansylated
      ketosteroids were detectable through laser-induced fluorescence at attomole
      levels, the CEC columns coupled to electrospray-ion-trap mass spectrometry
      featured femtomole detection limits.

PMID- 10961329
TI  - Separation and identification of etodolac and its urinary phase I metabolites
      using capillary electrochromatography and on-line capillary electrochromatography
      electrospray ionisation mass spectrometry coupling.
AB  - Capillary high-performance liquid chromatography (capillary HPLC), pressure
      assisted capillary electrochromatography (pCEC) and capillary
      electrochromatography (CEC) were performed in the same capillary packed with 5
      microm octadecylsilica (C18) as stationary phase. These three separation modes
      were compared from the viewpoint of peak efficiency and separation selectivity in
      order to critically evaluate the advantages which CEC may offer compared to
      capillary HPLC for the solution of practical biomedical problems. The separation
      of the non-steroidal anti-inflammatory drug etodolac (ET, 1) and its phase I
      metabolites, 6-hydroxy etodolac (6-OH-ET, 2), 7-hydroxy etodolac (7-OH-ET, 3) and
      8-(1'-hydroxyethyl) etodolac (8-OH-ET, 4) was selected as an example. Baseline
      separation of all compounds was achieved in different modes and conditions. The
      effect of pure electrophoretic separation mechanism on the overall separation
      selectivity observed in CEC has been shown. A high electroosmotic flow (EOF) was
      observed in C18 packed capillary even at pH 2.5 in various buffers. Furthermore,
      these separations were coupled on-line with electrospray ionisation mass
      spectrometry (ESI-MS) and the parent drug and its metabolites were identified in
      urine. For the coupling of CEC with ESI-MS a laboratory-made electrophoretic
      device was used in order to overcome some technical disadvantages of commercial
      instrumentation.

PMID- 10961330
TI  - Control of dispersion in capillary electrochromatography coupled to UV and mass
      spectrometric detection.
AB  - Capillary electrochromatography (CEC), along with other miniaturised
      chromatography techniques, such as capillary LC, offers the most benefit when
      efficiently coupled to mass spectrometric (MS) detectors. In conventional one
      piece CEC columns, dispersion in the open connecting tube between the packed
      column and MS source reduces chromatographic performance to unacceptable levels.
      This paper examines the effect on dispersion of various column-tube arrangements
      and offers suggestions as to the most practical way of connecting CEC-UV-MS.
      Comparisons of theoretical and measured values for these different arrangements
      are shown.

PMID- 10961331
TI  - Chiral anion exchangers applied to capillary electrochromatography
      enantioseparation of oppositely charged chiral analytes: investigation of
      stationary and mobile phase parameters.
AB  - Weak anion-exchange (WAX) type chiral stationary phases (CSPs) based on tert.
      butyl carbamoyl quinine as chiral selector (SO) and different types of silica
      particles (porous and non-porous) as chromatographic support are evaluated in
      packed capillary electrochromatography (CEC). Their ability to resolve the
      enantiomers of negatively charged chiral analytes, e.g., N-derivatized amino
      acids, in the anion-exchange mode and their electrochromatographic
      characteristics are described in dependence of several mobile phase parameters
      (pH, buffer type and concentration, organic modifier type and concentration) and
      other experimental variables (electric field strength, capillary temperature).
      The inherent "zwitterionic" surface character of such silica-based WAX type CSPs
      (positively charged SO and negatively charged residual silanols) allows the
      reversal of the electroosmotic flow (EOF) towards the anode at pH values below
      the isoelectric point (pI) of the modified surface, whereas a cathodic EOF
      results at pH values above the pI. Since for negatively charged analytes also an
      electrophoretic transport increment has to be considered, which can be either in
      or against the EOF direction, several distinct modes of elution have been
      observed under different stationary phase and mobile phase conditions: (i) co
      electrophoretic elution of the negatively charged solutes with the anodic EOF in
      the negative polarity mode, (ii) counter-electrophoretic elution with the
      cathodic EOF in the positive polarity mode, and (iii) electrophoretically
      dominated elution in the negative polarity mode with a cathodic EOF directed to
      the injection end of the capillary. Useful enantioseparations of chiral acids
      have been obtained with all three modes. Enantioselectivity values as high as
      under pressure-driven conditions and theoretical plate numbers up to 120000 per
      meter could be achieved under electrically driven conditions. A repeatability
      study yielded RSD values below 2% for retention times and RSD values in the range
      of 5-10% for theoretical plate numbers and resolution, thus clearly establishing
      the reliability of the investigated anion-exchange type CEC enantioseparation
      methods.

PMID- 10961332
TI  - Enantioseparations in non-aqueous capillary electrochromatography using
      polysaccharide type chiral stationary phases.
AB  - Enantioseparations of chiral compounds with different structures were studied in
      non-aqueous capillary electrochromatography (NAQ CEC). Three different
      polysaccharide derivatives, cellulose tris(3,5-dimethylphenylcarbamate)
      (Chiralcel OD), amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) and
      cellulose tris(4-methylbenzoate) (Chiralcel OJ) were used as chiral stationary
      phases (CSPs). Methanolic or ethanolic ammonium acetate solutions served as a
      mobile phase. The effect of the type of the CSP, the loading of the chiral
      selector on wide-pore aminopropyl derivatized silica gel and operational
      parameters such as apparent pH, applied voltage, etc. on the EOF and
      chromatographic characteristics (alpha, N, Rs) were studied. NAQ CEC represents a
      valuable alternative and an extension to chiral separations by HPLC with common
      size columns as well as to capillary LC and CEC in aqueous buffers.

PMID- 10961333
TI  - Enantiomer separations by capillary electrochromatography using chiral stationary
      phases.
AB  - The applicability of capillary electrochromatography (CEC) using packed capillary
      column to enantiomer separations was investigated. As chiral stationary phases,
      OD type packing materials of 5 and 3 microm particle diameters, originally
      designed for conventional high-performance liquid chromatography (HPLC) were
      employed. The chiral packing materials were packed by a pressurized method into a
      100 microm I.D. fused-silica capillary. Several racemic enantiomers, such as
      acidic, neutral and basic drug components, were successfully resolved, typically
      by using acidic or basic solutions containing acetonitrile as mobile phases. The
      separation efficiencies for some enantiomers in the chiral CEC system using the 5
      microm OD type packing were superior to those obtained in HPLC using chiral
      packings. The plate heights obtained for several enantiomers were 8-13 microm or
      the reduced plate height of 1.6-2.6, which indicates the high efficiency of this
      chiral CEC system.

PMID- 10961334
TI  - Capillary electrochromatography of proteins and peptides with a cationic acrylic
      monolith.
AB  - For the separation of proteins and peptides by capillary electrochromatography
      (CEC), columns with a monolithic stationary phase were prepared from silanized
      fused-silica capillaries of 50 microm I.D. by in situ copolymerization of
      glycidyl methacrylate, methyl methacrylate and ethylene glycol dimethacrylate in
      the presence of propanol and formamide as porogens. The epoxide groups at the
      surface of the porous monolith were reacted with N-ethylbutylamine to form fixed
      tertiary amino functions with ethyl- and butyl-chains. A mixture of ribonuclease
      A, insulin, alpha-lactalbumin and myoglobin was separated isocratically by
      counterdirectional CEC with hydro-organic mobile phases containing acetonitrile
      and sodium phosphate buffer, pH 2.5. The separation of four angiotensin type
      peptides by CEC was also achieved under similar conditions. The elution order of
      proteins was similar to that obtained in reversed-phase chromatography. Plots of
      the migration factors for proteins and peptides against the acetonitrile
      concentration exhibit opposite trends. This is most likely due to the greater
      chromatographic retention and lower electrophoretic migration velocity of
      proteins than that of peptides in the counterdirectional CEC system. From this it
      is concluded that the separation is governed by a dual mechanism that involves
      the complex interplay between selective chromatographic retention and
      differential electrophoretic migration.

PMID- 10961335
TI  - Comparison of separation behavior of benzodiazepines in packed capillary
      electrochromatography and open-tubular capillary electrochromatography.
AB  - Packed column capillary electrochromatography (CEC), open-tubular CEC and
      microcolum liquid chromatography (LC) using a cholesteryl silica bonded phase
      have been studied to compare the retention behavior for benzodiazepines. It has
      been found that packed column CEC gives better resolution, faster analysis time
      than microcolumn LC for benzodiazepines maintaining similar selectivity except
      for some solutes which are charged species under the separation conditions.
      However, open-tubular CEC gave different selectivities to a larger extent for
      charged benzodiazepines from that which should be produced by the chromatographic
      properties of the cholesteryl silica phase. Charged species migration times are
      mainly influenced by electrophoretic mobility rather than the chromatographic
      interactions.

PMID- 10961336
TI  - Analysis of hydroquinone and some of its ethers by using capillary
      electrochromatography.
AB  - Capillary electrochromatography (CEC) was used for the analysis of relevant
      compounds in cosmetic preparation. Hydroquinone (HQ) and some of its ethers
      (methyl-, dimethyl-, benzyl-, phenyl-, propyl-HQ derivatives) were analyzed by
      using an octadecylsilica (ODS) stationary phase packed in fused-silica capillary
      (100 microm I.D.; 30 cm and 21.5 cm total and effective lengths, respectively).
      20 mM Ammonium acetate pH 6-acetonitrile (50-70%) were the mobile phases used for
      the experiments. The acetonitrile (ACN) content strongly influenced the
      resolution of the studied compounds as well as the efficiency and the retention
      factor. Baseline resolution for the studied analytes was achieved at both the
      lowest and the highest percentage of ACN, the last one providing the shortest
      analysis time. Mobile phase containing 70% of ACN was therefore used for the
      analysis of an extract of skin-toning cream declared to contain HQ. Good
      repeatability of both retention times, peak areas and peak areas ratio
      (Asample/Ainternational standard) was found. The calibration graphs were linear
      in the concentration range studied (5-90 microg/ml) with correlation coefficients
      between 0.9975 and 09991. The analysis of the cosmetic preparation revealed the
      presence of HQ (1.72%, w/w) and of two additional peaks (not identified).

PMID- 10961337
TI  - Screening method for determining the presence of N-nitrosodiethanolamine in
      cosmetics by open-tubular capillary electrochromatography.
AB  - The presence of the carcinogenic N-nitrosodiethanolamine (NDELA; CAS No. 1116-54
      7) in cosmetic samples was determined using an etched, C18 modified capillary in
      the open-tubular capillary electrochromatography technique. A very simple
      extraction procedure leads to a sample matrix free from interferences. The
      calibration curve was created using UV detection at 214 nm. The detector response
      was linear in the range of 5-120 ppm total amount injected. Minimum detection
      limits (1 ppm NDELA injected on capillary) are suitable for screening a large
      number of cosmetic samples. Diethanolamine and triethanolamine precursors of
      nitrosamines are not detected at the wavelength used. Cosmetic samples were
      analyzed unspiked and after addition of 60 ppm of NDELA. In spiked samples
      recoveries varied from 94% (hand and body lotion) to 55% (lipstick sample). NDELA
      was found in unspiked samples of old (5-15 years old) cosmetics at concentrations
      of 14.0 ppm and 35.0 ppm.

PMID- 10961338
TI  - Introduction: the biology of the water molecule.

PMID- 10961340
TI  - Spectroscopy of aqueous solutions: protein and DNA interactions with water.
AB  - This review emphasises the need to use spectroscopy in order to understand the
      behaviour of water, and summarises the background of the subject. The various
      forms of spectroscopy that are especially informative are described, with
      particular reference to near-infrared (NIR) spectrophotometry. The key results
      are outlined, first those obtained with small molecules and ions, and second
      those involving proteins, DNA and cell membranes. Finally, some interpretations
      are offered which include the novel but possibly controversial concept of free OH
      and free lone-pair groups.

PMID- 10961339
TI  - Nuclear magnetic resonance studies of the hydration of proteins and DNA.
AB  - The behaviour of water in the presence of proteins and DNA as elucidated by
      nuclear magnetic resonance is reviewed. The picture that emerges is that in
      dilute solution only those water molecules in the interior of the biopolymers or
      in clefts have their motions substantially affected. In concentrated systems the
      situation is more complicated because many more motions have to be considered,
      but there is no evidence of special effects due to the biopolymers being present.
      The case of nonfreezing water in protein solutions is considered, and it is
      suggested that this is not evidence for 'bound' water but simply due to the
      effects of the inhibition of protein precipitation.

PMID- 10961341
TI  - Water in enzyme reactions: biophysical aspects of hydration-dehydration
      processes.
AB  - Water has been recognized as one of the major structuring factors in biological
      macromolecules. Indeed, water clusters influence many aspects of biological
      function, and the water-protein interaction has long been recognized as a major
      determinant of chain folding, conformational stability, internal dynamics,
      binding specificity and catalysis. I discuss here several themes arising from
      recent progress in understanding structural aspects of 'direct' and 'indirect'
      ligands in terms of enzyme-substrate interactions, and the role of water bridges
      in enzyme catalysis. The review also attempts to illuminate issues relating to
      efficiency, through solvent interactions associated with enzymic specificity, and
      versatility. Over the years, carbonic anhydrase (CA; carbonate hydrolyase, EC
      4.2.1.1) has played a significant role in the continuing delineation of
      principles underlying the role of water in enzyme reactions. As a result of its
      pronounced catalytic power and robust constitution CA was transformed into a
      veritable 'laboratory' in which active site mechanisms were rigorously tested and
      explored.

PMID- 10961342
TI  - Intracellular osmotic action.
AB  - Water often acts as a critical reactant in cellular reactions. Its role can be
      detected by modulating water activity with osmotic agents. We describe the
      principles behind this 'osmotic stress' strategy, and survey the ubiquity of
      water effects on molecular structures that have aqueous, solute-excluding
      regions. These effects are seen with single-functioning molecules such as
      membrane channels and solution enzymes, as well as in the molecular assembly of
      actin, the organization of DNA and the specificity of protein/DNA interactions.

PMID- 10961343
TI  - The invasion-associated type III secretion system of Salmonella typhimurium:
      common and unique features.
AB  - Several bacterial pathogens make use of a specialized protein secretion system to
      inject effector proteins into host cells. This system, commonly referred to as
      type III secretion, is always associated with phenotypes related to intimate
      interactions between the pathogen and its respective host cells. The enteric
      pathogen Salmonella typhimurium utilizes a type III secretion system to invade
      nonphagocytic intestinal epithelial cells. Whereas the invasion-associated type
      III system of S. typhimurium has evolved to perform a specific function, many of
      the components of this system are conserved among the type III systems of other
      bacterial pathogens. This review will discuss the common and unique features of
      the S. typhimurium system in relation to the type III systems of other human
      pathogens. Topics discussed include the phenotypes associated with various type
      III systems, the genetic loci encoding these systems, the components of the type
      III secretion apparatus, the effector proteins and the mechanisms by which they
      enter host cells as well as the mechanisms used to regulate the expression of
      type III systems.

PMID- 10961344
TI  - Structure and function of the type 1 insulin-like growth factor receptor.
AB  - The type 1 insulin-like growth factor receptor (IGF-1R), a transmembrane tyrosine
      kinase, is widely expressed across many cell types in foetal and postnatal
      tissues. Activation of the receptor following binding of the secreted growth
      factor ligands IGF-1 and IGF-2 elicits a repertoire of cellular responses
      including proliferation, and the protection of cells from programmed cell death
      or apoptosis. As a result, signalling through the IGF-1R is the principal pathway
      responsible for somatic growth in foetal mammals, whereas somatic growth in
      postnatal animals is achieved through the synergistic interaction of growth
      hormone and the IGFs. Forced overexpression of the IGF-1R results in the
      malignant transformation of cultured cells: conversely, downregulation of IGF-1R
      levels can reverse the transformed phenotype of tumour cells, and may render them
      sensitive to apoptosis in vivo. Elevated levels of IGF-IR are observed in a
      variety of human tumour types, whereas epidemiological studies implicate the IGF
      1 axis as a predisposing factor in the pathogenesis of human breast and prostate
      cancer. The IGF-1R has thus emerged as a therapeutic target for the development
      of antitumour agents. Recent progress towards the elucidation of the three
      dimensional structure of the extracellular domain of the IGF-1R represents an
      opportunity for the rational assembly of small molecule antagonists of receptor
      function for clinical use.

PMID- 10961346
TI  - Expression and cellular distribution of perchloric acid-soluble protein is
      dependent on the cell-proliferating states of NRK-52E cells.
AB  - To clarify the biological role of kidney perchloric acid-soluble protein 1 (K
      PSP1), its expression and intracellular distribution were examined in normal rat
      kidney epithelial NRK-52E cells. K-PSP1 expression was low during the
      proliferating phase and high in the stationary phase, and shown to have a
      negative relationship with the protein-synthesizing activity of the cells.
      Immunocytochemical studies revealed that K-PSP1 is predominantly located in the
      cytosol, especially in endoplasmic reticulum and Golgi apparatus of proliferating
      cells. In the stationary phase, K-PSP1 was not detected immunologically even
      though protein and mRNA expression were high. This disappearance of reactivity
      with anti-serum seems to be due to a conformational change in K-PSP1 induced by
      unknown factors. These results suggest that the role of K-PSP1 is to regulate
      cell proliferation, and this may be related to a previously reported ability to
      inhibit protein synthesis.

PMID- 10961345
TI  - MDR1, cholesterol certification and cell growth: a comparative study in normal
      and multidrug-resistant KB cell lines.

PMID- 10961347
TI  - Differential stimulation of signaling pathways initiated by Edg-2 in response to
      lysophosphatidic acid or sphingosine-1-phosphate.
AB  - Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are produced during
      cell activation and have multiple effects on cells. A family of seven
      transmembrane-spanning domain G-protein-coupled receptors, named Edg, mediate
      these effects of LPA and S1P. In this study, transient overexpression of Edg-2
      sensitized MG63 human osteosarcoma cells to both LPA- and S1P-mediated
      stimulation of fibronectin matrix deposition and actin stress fiber formation.
      Both lipids were active in the 1-20 nM concentration range on cells transfected
      with Edg-2 as compared to the 10-200 nM range on mock-transfected cells. The
      signaling pathway for matrix deposition by Edg-2-transfected cells was Rho
      dependent. Overexpression of Edg-2 also caused a tenfold decrease in the
      concentration of either LPA or S1P that activated MAPKinase (Erkl/2) in MG63
      cells. LPA- or S1P-stimulated activation of Erkl/2 was Gi dependent. These
      results indicate that, in MG63 cells, Edg-2 mediates actin stress fiber
      formation, fibronectin matrix assembly, and MAPKinase activation in response to
      either LPA or S1P.

PMID- 10961348
TI  - Ceramides induce apoptosis in HeLa cells and enhance cytochrome c-induced
      apoptosis in Xenopus egg extracts.
AB  - Ceramide has been reported to induce typical apoptotic changes in nuclei
      incubated in a cell-free system, and that the addition of ceramide bypasses the
      requirement for mitochondria. Here, we explore the possible pathways by which
      ceramide induces apoptosis either in intact cells or in a cell-free system which
      we have developed. We found that in the cell-free system, C2-ceramide is not able
      to induce apoptosis in nuclei whereas cytochrome c does, but it is able to induce
      HeLa cells to undergo apoptosis. Ceramide is also not able to induce apoptosis
      when added into the cell-free system together with purified mitochondria. Further
      investigation showed that C2-ceramide at certain concentrations greatly increases
      nuclear apoptosis caused by cytochrome c in the cell-free system. From these
      results we conclude that the induction of apoptosis by ceramide may require
      intact cells in which some unknown signal transduction pathways are involved.

PMID- 10961349
TI  - Kinetics of BRCA1 regulation in response to UVC radiation.
AB  - To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to
      increasing doses of ultraviolet C. We observed an increase in BRCA1 protein
      levels above 78 J/m2. This increase was observed as early as 5 min after
      irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent
      with the previously published data. By pretreating with cycloheximide prior to
      irradiation, we observed a decrease in the protein half-life, from 3.5 h to 53
      min, suggesting that a decrease in protein half-life may cause the lower levels
      of BRCA1 after irradiation. We also observed an increase in BRCA1 mRNA within 15
      min of irradiation, followed by a decrease after 4 h. These data suggest that
      newly translated protein may contribute to increases in BRCA1 protein levels. The
      very rapid changes in BRCA1 support its role as a sensor of DNA damage, as
      opposed to being a repair gene.

PMID- 10961350
TI  - Molecular cloning of a cDNA encoding alpha-glucosidase in the digestive gland of
      the shrimp, Litopenaeus vannamei.
AB  - The complete sequence of the 3-kb cDNA and the 5' genomic structure are reported
      for the gene encoding the shrimp alpha-glucosidase. Alpha-glucosidase cDNA was
      isolated from a shrimp digestive gland cDNA library. The 2830-base pair cDNA
      contains an open reading frame that encodes 919 amino acids. The shrimp alpha
      glucosidase cDNA shows a high level of identity with that of the human sucrase
      isomaltase, human maltase-glucoamylase, and human acid lysosomal alpha
      glucosidase, indicating that the protein shares the same structural domains. The
      similarities among these proteins are found as clusters and characterize the
      glycosyl hydrolase family 31. To our knowledge, this is the first report to
      describe a satellite sequence in the 5' genomic structure before the TATA box in
      an invertebrate sequence.

PMID- 10961351
TI  - Transplantations in patients with diabetes mellitus.

PMID- 10961352
TI  - Tamoxifen for breast cancer prevention.
AB  - Tamoxifen is of proven efficacy in the treatment of breast cancer. New data
      indicate that it might be able to reduce the occurrence of receptor positive
      breast cancer when taken as a preventative. However trade-offs for this reduction
      are an increased incidence of endometrial carcinomas and thromboembolic events.
      Therefore the use of tamoxifen as preventative ought to be restricted to clinical
      studies or a well defined high risk situation. Whether raloxifen is superior to
      tamoxifen remains to be shown.

PMID- 10961353
TI  - Asymptomatic primary hyperparathyroidism--need to treat?

PMID- 10961354
TI  - Cardiac transplantation in patients with insulin-treated diabetes mellitus.
AB  - BACKGROUND AND METHODS: As documented earlier the incidence of cardiac mortality
      in diabetic patients due to coronary artery disease is high. Cardiac
      transplantation for congestive heart failure due to coronary artery disease,
      cardiomyopathy, and valvular diseases is obviously a therapeutic option in
      patients suffering from insulin-treated diabetes mellitus. To shed more light on
      this problem we performed a retrospective analysis of 40 patients with insulin
      treated diabetes mellitus (three type-1; 37 type-2: insulin-treated for at least
      three months before cardiac transplantation) referred to our transplant unit for
      cardiac transplantation between March 1989 and December 1996. RESULTS: Orthotopic
      cardiac transplantation was performed in 40 patients (4 women, 36 men) aged 32-73
      years (mean 56 years) with an insulin-treated diabetes mellitus preexisting for 3
      348 months (mean 65.1 months). Donor age ranged from 15 to 72 years (mean 35.5
      years) matched for body weight and blood group. Overall mortality in this group
      was 40.0% with an early mortality of 12.5%. CONCLUSIONS: Our results show that
      type-1/2 insulin-treated diabetes mellitus preoperative to heart transplantation
      is not a contraindication in patients suffering from end-stage heart failure.
      Adequate therapy of diabetes mellitus as well as individual immunosuppressive
      therapy are important in order to minimize additional organ damage caused by the
      drugs themselves or resulting infectious complications.

PMID- 10961355
TI  - Glucose metabolism in children with renal failure: oral or intravenous glucose
      tolerance.
AB  - There is debate about the most suitable test for investigation of glucose
      tolerance in children with chronic renal failure. We therefore studied the
      agreement between the two most commonly used glucose tolerance tests in 33
      children with chronic renal failure (mean age 10.9+/-5.3 years, median GFR was 24
      ml/min/1.73 m2). All children underwent an oral glucose tolerance test (OGTT)
      with blood sampling up to 180 minutes and after an oral load of 1.75 g/kg and a
      standard intravenous glucose tolerance test (IVGTT) using 0.5 g/kg i.v. The two
      tests were performed at an interval of 23+/-5 days, with 9 patients having the
      OGTT before and 24 after the IVGTT. In order to account for the differing glucose
      load, a subgroup of 19 patients also received a glucose infusion test (GIT) using
      a total of 1.75 g/kg i.v. On IVGTT, 27 patients had a normal and 6 had a
      pathological glucose decay constant (k-value). On OGTT, 12 patients had an
      impaired glucose tolerance (IGT) and 3 patients were diabetic according to WHO
      standard, and only 18 patients had a normal glucose tolerance. While there was
      good correlation between both glucose and insulin concentrations between IVGTT
      and OGTT, only when reapplying the WHO criteria of a glucose concentration below
      6.7 mmol/l to the concentration measured 180 minutes instead of 120 minutes after
      oral glucose load, the agreement between the two tests improved. The proportion
      of normal findings on GIT when compared to OGTT was identical. When using the
      appropriate definitions for normal and abnormal carbohydrate tolerance,
      interestingly the insulin (IRI) concentrations on OGTT were not discriminative
      between the normal and the pathological group, whereas IRI first phase secretion
      on IVGTT and IRI 0-180 AUC on GIT did discriminate. We conclude that the standard
      WHO OGTT criteria may have to be reconsidered in children with chronic renal
      failure and that OGTT should be extended to 180 minutes. The IVGTT, particularly
      when insulin early phase secretion (at 0, 1, 3 and 5 minutes) is also monitored,
      provides a reliable test for assessing glucose tolerance in children with chronic
      renal failure.

PMID- 10961356
TI  - Elevated levels of leptin and insulin but not of TNF alpha are associated with
      hypertension in type 2 diabetic males.
AB  - Leptin and TNF alpha are thought to influence blood pressure. Therefore, the aim
      of our study was to investigate leptin and TNF alpha levels and their association
      with blood pressure, sex steroids, insulin, creatinine and lipids in type 2
      diabetic patients. In 424 type 2 diabetic patients (79 hypertensive females
      [+Hf], 79 normotensive females [-Hf]; 133 hypertensive males [+Hm], 133
      normotensive males [-Hm]) matched for sex, age and BMI serum leptin levels were
      measured by RIA and TNF alpha, insulin, estradiol, progesterone by ELISA as well
      as free testosterone by RIA. Leptin levels were comparable in +Hf and -Hf (16.5
      +/- 1.0 microg/l vs 16.3 +/- 1.0 microg/l) but higher in +Hm as compared to -Hm
      (8.3 +/- 0.47 microg/l vs 6.5 +/- 0.34 microg/l; p<0.05). In addition, in
      comparison to -Hm serum levels of insulin (190 +/- 10 pmol/l vs 161 +/- 11
      pmol/l; p< 0.005) and also of creatinine (118.6 +/- 3.6 micromol/l vs 101.7 +/-
      2.3; p< 0.0001) were higher in +Hm. Pearson's Correlation coefficient revealed a
      positive correlation between levels of leptin and diastolic blood pressure
      (p<0.05) and also between leptin and insulin (p<0.001) in males, however, only
      before correction for BMI. No correlation between leptin and creatinine was found
      in males and females. Levels of TNF alpha were comparable in all subgroups. No
      correlation between levels of TNF alpha and serum leptin levels, blood pressure
      and insulin was found. In females TNF alpha was positively correlated with
      creatinine (p<0.001) and in males positively with progesterone (p<0.001). Taken
      together, higher serum leptin levels were found in hypertensive type 2 diabetic
      males as compared to normotensives, which may be related to the BMI and higher
      levels of insulin. These findings are accompanied by a trend to lower levels of
      free testosterone in hypertensive type 2 diabetic males. TNF alpha levels were
      comparable in female and male hypertensive and normotensive type 2 diabetic
      subjects.

PMID- 10961357
TI  - How asymptomatic is asymptomatic primary hyperparathyroidism?
AB  - We observed several cases of patients who believed they were free of symptoms or
      signs of primary hyperparathyroidism (pHPT) preoperatively. reported a change of
      complaints following parathyroidectomy (PTX). We, therefore, decided to examine a
      larger group of patients to discover if these findings were incidental or of more
      general significance. The role of PTX in these patients with asymptomatic pHPT
      remains controversial. In 1991 criteria were defined at a NIH-consensus
      conference, according to which patients qualify for either operative therapy or
      long term medical surveillance. Until now, it was generally believed that the
      majority of asymptomatic patients would never develop symptoms. In a
      epidemiological cohort-study, the perioperative data of 582 consecutive patients
      with pHPT, including 116 asymptomatic patients (20.9%), who underwent
      parathyroidectomy between 1987 and 1998 were evaluated by uni- and multivariate
      analysis. At a median of 72 months postoperatively, all patients underwent a
      planned follow-up which included a standardised, validated questionnaire,
      physical examination and laboratory investigations. Eighty-six patients who were
      asymptomatic preoperatively were available for follow-up. Only eight (9.3%) were
      definitely asymptomatic, 4.6% of the entire, representative cohort. Postoperative
      improvement was reported in 81.4% of the "asymptomatic" patients. Multivariate
      analysis did not reveal a single or a set of preoperative measurements, that
      would allow to predict the retrospectively definitely asymptomatic patient. PTX
      resulted in normocalcaemia in 98.8% of preoperatively asymptomatic patients, with
      an operative morbidity of 1.2% and no mortality. Many apparently asymptomatic
      patients with pHPT will only realise that they did in fact have preoperative
      symptoms in retrospect, following PTX. This study suggests that using an up-to
      date definition of asymptomatic pHPT, there are only a small number of truly
      asymptomatic patients and that these cannot be predicted preoperatively, as their
      symptoms may become apparent only after PTX. "Asymptomatic" patients with pHPT
      may share the same objective and subjective benefits from PTX as symptomatic
      patients. They should be operated as soon as the diagnosis is established.

PMID- 10961358
TI  - Inhibition of proliferation and differentiation by RU 486 in human endometrial
      stromal and epithelial cells in vitro.
AB  - The effects of progesterone and RU 486 on cellular proliferation and
      differentiation in long term cultures of mixed human endometrial cells were
      studied. The endometrial tissue was obtained from women with normal menstrual
      cycles who were undergoing hysterectomy for benign growths. Estradiol
      supplemented cultures were treated with progesterone and/or RU 486 for 27 days.
      Cell number was measured by crystal violet assay, and prolactin secretion was
      used as a marker of differentiation. Progesterone doubled the rate of
      proliferation, but the addition of RU 486 reduced it to baseline again. The
      gestagen increased prolactin secretion up to 30 times, while the addition of RU
      486 suppressed it to baseline levels. When administered to cells that were
      pretreated with progesterone for 15 days RU 486 abolished the progesterone
      effects. RU 486 alone was without any effect. Our results indicate that (1) in
      vitro progesterone is essential for the initiation and maintenance of
      proliferation and differentiation of endometrial cells and (2) RU 486 acts as a
      pure progesterone antagonist in our culture model.

PMID- 10961359
TI  - The influence of hyperthyroidism on the hypothalamic-pituitary-gonadal axis.
AB  - We have investigated the function of the hypothalamic-pituitary-gonadal (H-P-G)
      axis in patients with severe, untreated Graves' disease. We studied 7 male and 6
      female healthy volunteers, and 7 male and 7 female patients with Graves' disease.
      Hormone profiles were developed by blood sampling every 10 min for an 8 hour
      period. In women this was done in the early follicular phase of menstrual cycle.
      LH-, FSH-, and PRL levels were measured using immunoradiometric assays and
      testosterone (T), estradiol (E2), sex-hormone binding globulin (SHBG), and
      progesterone (P) were measured with standard assays. The pulsatility of LH, FSH
      and PRL was calculated using the programmes Pulsar, Cluster and Desade. The
      temporal relationship of plasma LH, FSH, and PRL pulses was also investigated
      using specific concordance analysis. Data were evaluated by means of non
      parametric statistics. LH-secretion was increased in all hyperthyroid patients,
      while FSH-secretion was increased in hyperthyroid men only. Pulsatile
      characteristics of LH- and FSH-secretion (frequency, peak shape) in patients were
      not different from controls. No change in PRL-secretion was shown. Significant
      copulsatility occurred between LH and FSH, and LH and PRL. This was more
      pronounced in hyperthyroid than in healthy study subjects. Plasma levels of
      steroid hormones and sex-hormone-binding globulin were significantly (p<0.005)
      increased in hyperthyroid men. Free Androgen Index was significantly (p<0.005)
      decreased in hyperthyroid males. No other auto immune diseases were noticed. Our
      results indicate that the function of the H-P-G axis is not impaired in
      hyperthyroid patients, but gonadotropin levels are increased. Hyperthyroid men
      show relative primary gonadal insufficiency that may be due to exaggerated SHBG
      levels. The copulsatility of LH and FSH, and of LH and PRL was confirmed both in
      patients and controls.

PMID- 10961360
TI  - Follow up of thyroid hormone parameters in chronically ill geriatric patients:
      screening for thyroid disorders at hospital admission justified.
AB  - The objective of this study was to investigate if screening of chronically ill
      geriatric patients for thyroid dysfunction is justified just upon hospital
      admission. TSH was measured in 124 patients at hospital admission and 11-86
      (Median 37) days afterwards. FT4 was measured in cases with subnormal, suppressed
      or elevated TSH (43 cases). Out of 81 patients with normal (0.5-3.6 mU/l) TSH,
      the control value was subnormal (0.1-<0.5 mU/l) in 6 and elevated (>3.6 mU/l) in
      one case, but in none of the patients became suppressed (<0.1 mU/l). In 13/30
      patients with subnormal TSH the control value was normal but in none of the
      patients suppressed or elevated. On the contrary, all cases with suppressed (N=9)
      or elevated (N=4) TSH remained in the same ranges at follow up. Low (<13 pmol/l,
      N=3) or elevated (>27 pmol/l, N=5) initial FT4 levels did not change in the
      follow up as well. Out of 35 patients with normal FT4, one became low and another
      elevated. Improvement or worsening of the clinical state in the follow up did not
      correlate to changes of TSH. The prevalence of unsuspected thyroid dysfunctions
      were 11.3% (hyperthyroidism clinical: 4, subclinical: 5, hypothyroidism clinical:
      3, subclinical: 2 cases). All cases except one with subclinical hypothyroidism
      were detected by the initial screening. Only one patient with clinical
      hyperthyroidism was initial misinterpreted as having subclinical disease.
      CONCLUSIONS: In chronically ill geriatric patients investigated at hospital
      admission, a measurable TSH practically excludes hyperthyroidism in the follow
      up. Suppressed TSH levels remain suppressed but subnormal levels should be
      controlled because their normalization frequently occur in the follow up.
      Screening upon hospital admission is sensitive enough to detect cases of thyroid
      dysfunction and justified by their high prevalence.

PMID- 10961361
TI  - Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's
      syndrome and in patients with adrenal incidentaloma.
AB  - It is known that either chronic glucocorticoid administration or endogenous
      hypercortisolism frequently induce an hypercoagulable condition. Since little is
      known about the evaluation of markers of haemostatic and fibrinolytic systems in
      other adrenal disorders, we studied plasminogen activator inhibitor (PAI-1),
      tissue-plasminogen activator (t-PA), fibrinogen and von Willebrand factor antigen
      (vWF-Ag) levels in 11 patients with Cushing's syndrome and in 12 patients with
      adrenal incidentaloma. In patients with Cushing's syndrome mean PAI-1, t-PA and
      vWF-Ag levels did not significantly differ from those found in 50 age- and sex
      matched controls, while mean fibrinogen levels were significantly higher in
      patients (337.0+/-39.1 mg/dl) than in normal subjects (278.9+/-8.4 mg/dl).
      Patients with adrenal incidentaloma showed PAI-1, t-PA and vWF-Ag mean levels
      superimposable to those in controls, while fibrinogen (319.7+/-27.9 mg/dl) was
      slightly, although not significantly, higher than in normals. Considering the
      limits of normal values (as mean+/-2 SD) obtained in the control group, high PAI
      1 levels were found in 2 patients with Cushing's syndrome and in 3 patients with
      incidentaloma. An elevation of fibrinogen levels was found in 3 patients with
      Cushing's syndrome and in 3 with incidentaloma. Increased vWF-Ag levels were
      found only in 1 patient with Cushing's syndrome. An increased t-PA level was
      occasionally observed only in the patient with adrenal carcinoma. On the whole,
      an alteration of at least one of haemostatic and fibrinolytic parameters was
      detected in 55% of the patients with Cushing's syndrome and in 42% of those with
      adrenal incidentaloma. In conclusion, early alterations of coagulation and
      fibrinolytic systems may be found in some patients with adrenal disorders, thus
      suggesting the opportunity of an accurate follow-up in order to identify possible
      risk factors for cardiovascular disease and thromboembolism.

PMID- 10961362
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters follicular steroidogenesis in time-
      and cell-specific manner.
AB  - To show the direct effect of TCDD on ovarian steroidogenesis theca (Tc) and
      granulosa (Gc) cells were cultured separately or as a co-culture (GT). Cells were
      cultured in M199 medium supplemented every day with 0.1 nM TCDD or only at the
      beginning of the culture with 10 nM of TCDD. After 48, 96 and 144 h culture media
      were collected for steroids content analysis. In Tc cultured alone TCDD caused an
      increase in E2 production after 48 and 96 h of culture, while exposure of Tc on
      TCDD for 144 h caused the decrease in both T and E2 secretion. In Gc cultured
      alone and in GT cultures the increase in E2 secretion was observed only after 48
      h, while a long term exposure to TCDD (96 and 144 h) caused a decrease of both P4
      and E2 secretion. The results of the present study suggest various, time
      dependent mechanisms of TCDD action on ovarian cells.

PMID- 10961363
TI  - Palm vitamin E is comparable to alpha-tocopherol in maintaining bone mineral
      density in ovariectomised female rats.
AB  - Vitamin E has been shown to affect bone metabolism. In this study we determined
      the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague
      Dawley female rats fed with normal rat chow were divided into 4 groups and
      supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60
      mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not
      supplemented. Half of these rats were ovariectomised before supplementation was
      given for 10 months. As expected, bone mineral density of the ovariectomised rats
      fed on normal rat chow diet was lower compared to the intact rats. However, these
      changes were not seen in the supplemented group of rats. Both intact and
      ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a
      lower bone calcium content in both femoral and vertebral bones whilst rats fed
      palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were
      able to maintain bone calcium content. Alkaline phosphatase activity was elevated
      in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and
      alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha
      tocopherol also reduced the activity of tartrate-resistant acid phosphatase post
      ovariectomy. These findings indicate that both palm vitamin E and alpha
      tocopherol maintained bone mineral density in ovariectomised rats but caused
      conflicting effects on bone calcium content. Further study is needed in order to
      determine the mechanisms involved.

PMID- 10961364
TI  - Age-related differences in the expression of receptors for TGF-beta in human
      osteoblast-like cells in vitro.
AB  - The cell surface expression of receptors for TGF-beta was studied in human
      osteoblasts derived from femoral trabecular bone of a total of 19 patients aged 2
      83 years. All cell populations investigated showed a similar profile of
      expression of TGF-beta receptors (TbetaR) I, II and III (betaglycan). There were
      no significant differences in cell differentiation or proliferative behaviour
      between the age groups. The TGF-beta receptor number per cell significantly
      increased with age, while the receptor affinity tended to decrease. IGF-I did not
      influence TbetaR expression in vitro. The results indicate an age-dependent and
      IGF-I independent increase of osteoblastic TGF-beta receptors in human osteoblast
      like cells in vitro.

PMID- 10961365
TI  - Fluvastatin combined with 17beta-estradiol: effect on the oxidation of human low
      density lipoprotein.
AB  - The in vitro effect of a statin and an estrogen on oxidation of human LDL was
      investigated for the first time, comparing the monosubstances fluvastatin and
      17beta-estradiol as well as the effect of the combination. Fluvastatin
      significantly delayed the onset of LDL oxidation (controls = 90 min) by 23 min at
      1 microM, by 110 min and by 221 min at 5 and 10 microM, respectively. 17Beta
      estradiol significantly impeded the onset by 70 min at 1 microM and by more than
      300 min at 5 and 10 microM. The combination of 1 microM 17beta-estradiol with 1,
      5 and 10 microM fluvastatin showed an additive antioxidative effect; the onset
      was delayed by 100 min, by 167 min and by more than 300 min, respectively. It can
      be concluded that treatment of postmenopausal women with fluvastatin and 17beta
      estradiol may have not only beneficial effects on lipid disorders but may also
      elicit a direct potent anti-atherosclerotic action on the vasculature.

PMID- 10961366
TI  - Retroperitoneal schwannoma presenting as an adrenal tumor.
AB  - A retroperitoneal tumor in the region of the adrenal gland was diagnosed in a 56
      year-old woman. The patient had been suffering from a dull abdominal pain for
      nearly four weeks before consulting her family physician. Ultrasound, CT and MRI
      scans revealed a giant tumor of the right adrenal gland. Endocrine activity could
      not be demonstrated. The size of the tumor was suggestive of an adrenal
      carcinoma. The patient was referred for adrenalectomy and complete exstirpation
      of the retroperitoneal mass. The histological examination revealed
      characteristical findings of a benign schwannoma.

PMID- 10961367
TI  - Obesity--the need for an interdisciplinary approach to the prevention and
      treatment of a global epidemic.

PMID- 10961368
TI  - Diabetes insipidus and malignant B-cell lymphoma.

PMID- 10961369
TI  - The calcium antagonist nifedipine inhibits the uptake of acetylated LDL into
      endothelial cells.
AB  - The uptake of LDL and modified LDL into macrophages via specific receptors is one
      of the crucial steps during atherogenesis. Recently, similar receptors for
      acetylated and oxidized LDL were characterized in endothelial cells. It is known
      that dihydropyridine calcium antagonists may attenuate the formation of
      atherosclerotic plaques presumably by an increased nitric oxide (NO) release from
      endothelial cells. Therefore, we investigated whether the uptake of acetylated
      LDL into endothelial cells may be altered by the calcium antagonist nifedipine
      with special emphasis on the NO metabolism. Treatment of porcine endothelial cell
      cultures with nifedipine induced a significant concentration-dependent inhibition
      of the uptake of acetylated LDL. This effect could be completely prevented by
      coincubation with L-nitro-N-arginine, a competitive NO synthase inhibitor.
      Treatment with the NO donor SNAP resulted in a similar significantly reduced
      uptake of acetylated LDL. To test whether this effect is due to an NO-mediated
      cGMP mechanism, we incubated cells with 8-bromo-cGMP and coincubated cells with
      nifedipine and the soluble guanylyl cyclase inhibitor ODQ. 8-bromo-cGMP partly
      mimicked the nifedipine effect and ODQ partly reversed the nifedipine effect but
      not to a significant extent. Therefore, we conclude that the calcium antagonist
      nifedipine inhibits the uptake of acetylated LDL into endothelial cells via an NO
      but presumably not by a cGMP-mediated process, which may possibly contribute to
      the antiatherogenic action of this drug.

PMID- 10961370
TI  - Does serotonin relax the rat anococcygeus muscle via 5-HT7 receptors?
AB  - The mechanisms of serotonin (5-HT)-induced contraction and relaxation were
      studied in the rat anococcygeus muscle. In the presence of prazosin (1 nM) and
      ketanserin (10 nM), concentration/response curves to 5-HT were shifted to the
      right and the maximum effects were not affected (pKB values 9.09+/-0.29 and
      8.66+/-0.06 for prazosin and ketanserin, respectively). On contrary, guanethidine
      (10 microM) antagonised the 5-HT-induced contractions non-competitively. In the
      presence of guanethidine, prazosin or ketanserin further inhibited the responses
      to 5-HT at lower concentrations. The serotonergic receptor agonists 5
      carboxamidotrypamine, metoclopramide and sumatriptan did not produce any effect
      in tissues under baseline conditions. 5-HT caused concentration-dependent
      relaxation in phenylephrine (1 microM) -precontracted preparations in the
      presence of guanethidine (10 microM). Tetrodotoxin (1 microM), N(G)-nitro-L
      arginine (100 microM) and capsaicin (1 microM) were ineffective in antagonising
      the relaxation induced by 5-HT. The serotonergic receptor antagonists: ketanserin
      (0.1 microM), ICS 205930 (10 microM), GR 113808 (10 microM), GR 55562 (10
      microM), methiothepin (10 nM), mesulergine (10 microM), ritanserin (0.1 microM)
      and spiperon (0.1 microM) did not antagonise 5-HT-induced relaxation. On the
      other hand, clozapine (0.01-0.1 microM) and metergoline (0.1-1 microM) attenuated
      the relaxation induced by 5-HT. These results demonstrate that 5-HT contracts rat
      anococcygeus muscle directly by an action on alpha1-adrenergic receptors and
      indirectly by releasing noradrenaline from adrenergic nerve endings. None of the
      5-HT receptors plays a role in the 5-HT-induced contractions. Moreover 5-HT
      induces concentration-dependent relaxation in the precontracted preparations
      which apparently are not mediated through known 5-HT receptor types.

PMID- 10961371
TI  - Autoradiographic mapping of mu-opioid receptors during opiate tolerance and
      supersensitivity in the rat central nervous system.
AB  - In this autoradiographic study we have analysed the regional changes in the
      density of mu-opioid receptors produced by the chronic administration of
      sufentanil alone and after concurrent administration with nimodipine. mu-Opioid
      receptors in the central nervous system (CNS) of rats were labelled using 5 nM
      [3H]DAMGO. Sufentanil, a high-efficacy agonist, was administered for 7 days by
      chronic infusion (2 microg/h). Another group of animals received a simultaneous
      infusion of sufentanil (2 microg/h) and nimodipine (1 microg/h) for 7 days. These
      two drug regimes have been previously shown to induce tolerance and
      supersensitivity to the analgesic effect of the opioid, respectively. Our results
      clearly demonstrate that opioid tolerance is associated with a generalised down
      regulation of mu-opioid binding sites throughout the brain and the spinal cord.
      Compared with the findings in tolerant animals, the CNS of animals supersensitive
      to sufentanil showed less down-regulation of mu-opioid receptors, to the extent
      that, particularly in brain areas related to nociception, such as the
      somatosensory cortex, central grey, raphe magnus nucleus and dorsal horn of the
      spinal cord, no down-regulation occurred. These neurochemical findings may
      contribute to the functional interaction between nimodipine and sufentanil that
      we have previously observed in analgesic studies.

PMID- 10961373
TI  - Affinity, potency and efficacy of tramadol and its metabolites at the cloned
      human mu-opioid receptor.
AB  - The present study was conducted to characterise the centrally active analgesic
      drug tramadol hydrochloride [(1RS,2RS)-2-[(dimethyl-amino)-methyl]-1-(3
      methoxyphenyl)-cyclohe xanol hydrochloride] and its metabolites M1, M2, M3, M4
      and M5 at the cloned human mu-opioid receptor. Membranes from stably transfected
      Chinese hamster ovary (CHO) cells were used to determine the four parameters of
      the ligand-receptor interaction: the affinity of (+/-)-tramadol and its
      metabolites was determined by competitive inhibition of [3H]naloxone binding
      under high and low salt conditions. The agonist-induced stimulation of
      [35S]GTPgammaS binding permits the measurement of potency (EC50), efficacy (Emax
      = maximal stimulation) and relative intrinsic efficacy (effect as a function of
      receptor occupation). The metabolite (+)-M1 showed the highest affinity (Ki=3.4
      nM) to the human mu-opioid receptor, followed by (+/-)-M5 (Ki=100 nM), (-)-M1
      (Ki=240 nM) and (+/-)-tramadol (Ki=2.4 microM). The [35S]GTPgammaS binding assay
      revealed an agonistic activity for the metabolites (+)-M1, (-)-M1 and (+/-)-M5
      with the following rank order of intrinsic efficacy: (+)-M1>(+/-)-M5>(-)-M1. The
      metabolites (+/-)-M2, (+/-)-M3 and (+/-)-M4 displayed only weak affinity (Ki> 10
      microM) and had no stimulatory effect on GTPgammaS binding. These data indicate
      that the metabolite (+)-M1 is responsible for the mu-opioid-derived analgesic
      effect.

PMID- 10961372
TI  - Expression and function of beta-glucuronidase in pancreatic cancer: potential
      role in drug targeting.
AB  - Improvement of non-surgical strategies is a pivotal task in the treatment of
      pancreatic cancer. Response to treatment with most anticancer agents has been
      very poor, probably due to insufficient drug concentration in tumor tissue.
      Increased response rates during chemotherapy might be achieved by dose
      escalation; however, this approach is often hampered by severe side effects. One
      strategy to overcome these adverse effects is application of nontoxic glucuronide
      prodrugs from which the active moiety is released by beta-glucuronidase within or
      near the tumor. The use of glucuronide prodrugs in pancreatic cancer requires
      increased expression of the enzyme in the diseased tissue, a problem that has not
      been addressed so far. We therefore investigated function and expression of beta
      glucuronidase in tissue samples from human healthy pancreas (n=7) and pancreatic
      adenocarcinoma (n=8), respectively. Comparing the ability of tissue homogenates
      to cleave the standard substrate 4-methylumbelliferyl-beta-D-glucuronide, we
      found a significantly increased specific beta-glucuronidase activity (P<0.05) in
      pancreatic cancer (median: 133; 75% percentile: 286; 25% percentile: 111 nmol/mg
      per h) as compared to healthy pancreas (median: 74; 75% percentile: 113; 25%
      percentile: 71 nmol/mg per h). Enzyme kinetic experiments with the model prodrug
      N-[4-beta-glucuronyl-3-nitrobenzyloxycarbonyl] doxorubicin (HMR 1826)
      demonstrated bioactivation of HMR 1826 by pancreatic beta-glucuronidase.
      Enzymatic activity was found to be closely related to enzyme contents (r=0.87) as
      assessed by Western blot analysis. Our data indicate that increased beta
      glucuronidase activity in pancreatic cancer seems to be due to an elevated steady
      state level of the protein. This may be the basis for new therapeutic strategies
      in treatment of pancreatic carcinoma by using glucuronide prodrugs of anticancer
      agents.

PMID- 10961374
TI  - Stimulatory effect of caffeic acid on alpha1A-adrenoceptors to increase glucose
      uptake into cultured C2C12 cells.
AB  - In an attempt to understand the antihyperglycemic action of caffeic acid, the
      myoblast C2C12 cells were employed to investigate the glucose uptake in the
      present study. Caffeic acid enhanced the uptake of radioactive glucose into C2C12
      cells in a concentration-dependent manner. Similar effect of phenylephrine on the
      uptake of radioactive glucose was also observed in C2C12 cells. Prazosin
      attenuated the action of caffeic acid in a way parallel to the blockade of
      phenylephrine. Effect of caffeic acid on alpha1-adrenoceptors was further
      supported by the displacement of [3H]prazosin binding in C2C12 cells. Moreover,
      the glucose uptake-increasing action of phenylephrine in C2C12 cells was
      inhibited by the antagonists of alpha1A-adrenoceptors, both tamsulosin and WB
      4101, but not by the antagonist of alpha1B-adrenoceptors, chlorethylclonidine
      (CEC). The presence of alpha1A-adrenoceptors in C2C12 cells can thus be
      considered. Similar inhibition of the action of caffeic acid was also obtained in
      C2C12 cells co-incubating these antagonists. An activation of alpha1A
      adrenoceptors seems responsible for the action of caffeic acid in C2C12 cells. In
      the presence of U73312, the specific inhibitor of phospholipase C, caffeic acid
      stimulated uptake of radioactive glucose into C2C12 cells was reduced in a
      concentration-dependent manner and it was not affected by U73343, the negative
      control of U73312. Moreover, chelerythrine and GF 109203X diminished the action
      of caffeic acid at concentrations sufficient to inhibit protein kinase C.
      Therefore, the obtained data suggest that an activation of alpha1A-adrenoceptors
      in C2C12 cells by caffeic acid may increase the glucose uptake via phospholipase
      C-protein kinase C pathway.

PMID- 10961375
TI  - Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on
      endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin
      release.
AB  - Endothelins are a family of potent endogenous mediators that have been implicated
      in a number of airway and other diseases. Recently, the non-peptide mixed
      ET(A)/ET(B) endothelin receptor antagonist bosentan has been successfully tested
      in the treatment of cardiovascular diseases. It was the aim of the present study
      to characterize the effects of bosentan on the pulmonary actions of endothelin-
      (ET-1), endothelin-3 (ET-3) and the ET(B)-receptor agonist IRL1620 in the
      isolated perfused and ventilated rat lung (IPL) and in precision-cut lung slices
      (PCLS). In the IPL, bosentan completely prevented the IRL1620-induced
      vasoconstriction (IC50 3 microM). The inhibition by bosentan of ET-1-elicited
      vasoconstriction showed a biphasic course, reflecting the inhibition of ET(A)-and
      ET(B)-mediated vasoconstriction (IC50 0.2 microM and 19 microM, respectively). In
      addition, bosentan prevented the ET-1- (IC50 6 microM) and IRL1620-induced (IC50
      3 microM) prostacyclin release. Bosentan also completely prevented the
      bronchoconstriction induced by IRL1620 in the IPL (IC50 20 microM) and in PCLS
      (IC50 13 microM). In PCLS, the pD2-values were ET-1 7.20+/-0.23, ET-3 7.51+/-0.27
      and IRL1620 7.33+/-0.29. Bosentan at 100 microM caused a rightward shift of the
      concentration-response curve of ET-1, ET-3 and IRL1620 by a factor of 5, 46 and
      64, respectively. In all cases the slope of the Schild regression was lower than
      unity, disregarding a simple interaction of bosentan with one receptor. With
      respect to ET-1-induced bronchoconstriction, in the IPL bosentan in
      concentrations of up to 10 microM aggravated ET-1-induced bronchoconstriction
      probably due to the blockade of bronchodilatory ET(A)-receptors (IC50 0.3 microM)
      and even at 100 microM showed only very little protection from ET- -induced
      bronchoconstriction in the IPL and in the PCLS. The similar IC50-values for ET-1
      induced vasoconstriction and bronchodilation suggest that only one type of ET(A)
      receptor is involved. The differing IC50-values between IRL1620-induced
      bronchoconstriction and prostacyclin release, the slope of the Schild regression
      and the failure of bosentan to prevent the ET-1-induced bronchoconstriction
      suggest a complex interaction between the known ET-receptors or the existence of
      unknown ET(B)-receptor subtypes.

PMID- 10961376
TI  - Pharmacological investigation into the involvement of nitric oxide in K+-induced
      cortical spreading depression.
AB  - Cortical spreading depression (CSD) is a transient, local disruption of cellular
      ionic homeostasis that propagates slowly across the cerebral cortex. As previous
      data have suggested a possible link between nitric oxide (NO) formation and CSD,
      we have examined whether CSD is suppressed by local inhibition of NO synthesis
      with 7-nitroindazole (7-NINA), a compound which may have a greater selectivity
      for the neuronal NO synthase isoform. Multifunctional microdialysis probes were
      implanted in the cortex of halothane-anaesthetised rats, and used for (1)
      elicitation of repetitive CSD by perfusion of 160 mM K+ through the probe, (2)
      recording of CSD as a negative shift of the extracellular direct current (DC)
      potential, and (3) perfusion of 7-NINA before and during CSD elicitation.
      Elicitation of CSD was moderately inhibited by 1 mM 7-NINA in the perfusion
      medium, as shown in one treated group (n=8) by a significant reduction of both
      number (from 5.1+/-0.4 to 3.6+/-0.4; P<0.05) and cumulative DC negativity (from
      16.4+/-0.7 mV x min to 13.3+/-0.9 mV x min; P<0.01). However, effective
      concentrations of 7-NINA were at least 100-fold higher than its Ki for the target
      enzyme in vitro, the moderate inhibition of CSD by 7-NINA was not reversed by the
      NO precursor, L-arginine, and the amplitude of the K+-induced sustained DC
      potential negative shift was also reduced significantly by 7-NINA (from 27.9+/
      0.9 mV to 23.9+/-1.2 mV; P<0.05). These data do not support the hypothesis that
      NO formation contributes to the elicitation of CSD by high extracellular K+. The
      finding that 7-NINA reduced the intensity of K+-induced depolarisation may be
      relevant to previous investigations that used this drug to examine the role of NO
      in the modulation of K+-induced neurotransmitter release.

PMID- 10961377
TI  - The identification of a potent imidazoline-based vascular K(ATP) channel
      antagonist.
AB  - In this study the activity of a number of novel imidazoline-based compounds (IMID
      series) was assessed by functional and binding studies to determine their actions
      at K(ATP) channels. The novel compounds, which we synthesised, were methoxy-,
      methyl-, butyl- and fluorophenyl derivatives of clonidine. In functional studies
      we determined the potency (by calculating a pK(B) value) of the IMID compounds to
      antagonise levcromakalim responses in segments of isolated pig coronary artery.
      The most potent compounds identified (laboratory codes: IMID-1M, IMID-26F and
      IMID-4F) had apparent pK(B) values of approximately 7 which is similar to that
      for the sulphonylurea, glibenclamide and the lipophilic quaternary ion,
      tetraphenylphosphonium. This inhibitory action was specific for levcromakalim
      since the imidazoline antagonist IMID-1M failed to effect vasorelaxation response
      curves to the non-KATP channel opener, sodium nitroprusside. In the spontaneously
      beating rat right atrium preparation the majority of the compounds were able to
      cause slowing of heart rate, but with low EC50 values (approximately 10-30
      microM). In binding studies, the compounds were unable to displace binding of
      [3H]P1075 to bovine aortic smooth muscle preparations nor [3H]glibenclamide
      binding to rat cerebral cortex membranes. These studies show that some
      imidazoline-based compounds are potent antagonists of levcromakalim-mediated
      vasorelaxation responses in the pig coronary artery. The compounds displayed only
      minimal bradycardic activity. The site of action of the imidazoline compounds
      does not appear to be the same as that used by K(ATP) channel openers or
      sulphonylurea-based antagonists. It is likely that these compounds interact with
      the K(ATP) channel pore itself.

PMID- 10961378
TI  - Abolition of endothelium-dependent relaxation in the rat aorta by
      tetraoctylammonium ions.
AB  - Quaternary ammonium ions are common pharmacological probes used to study the
      kinetic properties of K+ channels in smooth muscle cells. On the other hand, some
      ammonium compounds cause vasorelaxation through unknown mechanisms. The main aim
      of this study was to examine a unique role of endothelium in the vascular
      response to tetraoctylammonium ions (TOA+) in the isolated rat aorta. Changes in
      contractile force were measured by force transducers and total tissue content of
      cGMP was measured by radioimmunoassay. Endothelial cytosolic Ca2+ ([Ca2+]i) was
      assessed by laser scanning confocal microscopy.

PMID- 10961379
TI  - Comparison of the Ca2+ entry channels responsible for mechanical responses of
      guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908.
AB  - Noradrenaline (NA) produces sustained contractions in conduit arteries such as
      aorta isolated from various animal species. In guinea-pig aorta, NA-produced
      sustained contraction is largely dependent upon the influx of extracellular Ca2+,
      but is refractory to the treatment with organic Ca2+ entry blockers. In the
      present study, we attempted to characterize pharmacologically the Ca2+ entry
      channel responsible for NA-produced sustained contraction of guinea-pig aorta
      using SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H
      imi dazole) and LOE 908 ((R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2
      phenyl-N,N-di-[2- (2,3,4-trimethoxyphenyl)ethyl]-acetamide), both of which block
      voltage-independent Ca2+ channels. The effects of SK&F 96365 and LOE 908 on NA
      produced contraction were compared with those on extracellular Ca2+-dependent
      contractile and endothelium-dependent relaxant responses to thapsigargin (TSG),
      an inhibitor of Ca2+-pump Ca2+-ATPase. NA (3x10(-6) M)-produced sustained
      contraction of guinea-pig aorta without endothelium exhibited a strong dependency
      on the extracellular Ca2+. Nicardipine (10(-7) M), diltiazem (10(-5) M) and
      verapamil (10(-5) M) did not show any appreciable inhibitory effects on NA
      produced sustained contraction. SK&F 96365 concentration-dependently (10(-6)-10(
      4) M) attenuated the NA-produced sustained contraction whereas LOE 908 did not
      affect it at concentrations up to 10(-4) M. Similarly, extracellular Ca2+
      dependent contraction of guinea-pig aorta without endothelium in response to TSG
      was also diminished by SK&F 96365 but was unaffected by LOE 908. In fura-PE3
      loaded vascular preparations, SK&F 96365 decreased both cytoplasmic Ca2+ level
      ([Ca2+]i) and muscle tension elevated by NA and TSG. Both SK&F 96365 and LOE 908
      did not affect an endothelium-dependent relaxation of guinea-pig aorta in
      response to TSG. These findings suggest that in guinea-pig aortic smooth muscle
      cells, NA activates Ca2+ influx across the plasma-membrane through the Ca2+
      permeable channel which is identical with or has similar properties to the store
      operated Ca2+ channel (SOCC) stimulated by TSG, but is distinct from endothelial
      cell SOCC.

PMID- 10961380
TI  - Mediation of 5-HT-induced internal carotid vasodilatation in GR127935- and
      ritanserin-pretreated dogs by 5-HT7 receptors.
AB  - The vasoconstrictor effects of 5-hydroxytryptamine (5-HT) in the internal carotid
      bed of anaesthetised dogs with bilateral vagosympathectomy are mainly mediated by
      both 5-HT1B and 5-HT2 receptors. The blockade of this vasoconstrictor effect of 5
      HT by the combined use of the antagonists, GR127935 (5-HT1B/1D) and ritanserin (5
      HT2), unmasks a dose-dependent vasodilator effect of 5-HT, but not of
      sumatriptan. Therefore, the present study set out to analyse the pharmacological
      profile of this vasodilator 5-HT receptor in the internal carotid bed of
      vagosympathectomized dogs systematically pretreated with intravenous (i.v.)
      injections of GR127935 (30 microg/kg) and ritanserin (100 microg/kg). One-minute
      (1-min) intracarotid (i.c.) infusions of 5-HT (0.1-10 microg/min), 5
      carboxamidotryptamine (5-CT; 0.01-0.3 microg/min), 5-methoxytryptamine (5-MeO-T;
      1-100 microg/min) and acetylcholine (ACh; 0.003-0.1 microg/min) resulted in dose
      dependent increases in internal carotid blood flow (without changes in blood
      pressure or heart rate) with a rank order of agonist potency of ACh > 5-CT >> 5
      HT > or =5-MeO-T. The internal carotid vasodilator responses to 5-HT, 5-CT and 5
      MeO-T, which remained unaffected after saline (0.03 ml/kg and 0.1 ml/kg, i.v.),
      were specifically and dose-dependently blocked by i.v. administration of lisuride
      (10 microg/kg and 30 microg/kg), clozapine (1000 microg/kg), mesulergine (300
      microg/kg and 1000 microg/kg) and LY215840 (300 microg/kg and 1000 microg/kg)
      with the following apparent rank order of potency: lisuride >> mesulergine =
      LY215840 > or = clozapine. The above results suggest that the 5-HT receptor
      mediating internal carotid vasodilatation in vagosympathectomized dogs pretreated
      with GR127935 and ritanserin is operationally similar to other 5-HT7 receptors
      mediating vascular and non-vascular responses.

PMID- 10961381
TI  - The effect of SB-236057-A, a selective 5-HT1B receptor inverse agonist, on in
      vivo extracellular 5-HT levels in the freely-moving guinea-pig.
AB  - 5-HT1B autoreceptors are involved in the control of extracellular 5-HT levels
      from both the terminal and cell body regions of serotonergic neurones. In this
      study we report on the effect of a selective and potent 5-HT1B receptor inverse
      agonist, SB-236057-A (1'-ethyl-5-(2'-methyl-4'-(5-methyl- 1,3,4-oxadiazolyl-2
      yl)biphenyl-4-carbonyl)-2,3,6,7-tetrahydros piro [furo[2,3-f]indole-3,4' 
      piperidine] hydrochloride), on extracellular 5-HT levels in the cortex and
      dentate gyrus of the freely-moving guinea-pig, using the technique of in vivo
      microdialysis. SB-236057-A had ca. 23% bioavailability following oral drug
      administration. In vivo hypothermia pharmacodynamic assays demonstrated it was
      brain penetrant with a duration of action in excess of 18 h. SB-236057-A (0.75
      mg/kg p.o.) increased extracellular 5-HT levels in the dentate gyrus to a maximum
      of 167+/-7% of basal but had no effect in the frontal cortex. However, a small
      increase in cortical 5-HT levels (117+11% of basal) was evident at 2.5 mg/kg p.o.
      In addition, SB-236057-A (0.75 mg/kg and 2.5 mg/kg p.o.) antagonised the
      sumatriptan-induced inhibition of extracellular 5-HT levels in the guinea-pig
      frontal cortex. These differences were attributed to MRN-innervated regions (e.g.
      dentate gyrus) being more responsive to 5-HT1B receptor-mediated negative
      feedback than DRN-innervated regions (e.g. frontal cortex). In the dentate gyrus,
      the increase in 5-HT release induced by SB-236057-A (0.75 mg/kg p.o.) was
      comparable to that after 14 days of paroxetine (10 mg/kg p.o.) administration,
      reaching a maximum of 183+/-13% of basal. These data suggest that acute 5-HT1B
      receptor blockade, by virtue of increased 5-HT release in the dentate gyrus, may
      provide a rapidly acting antidepressant.

PMID- 10961382
TI  - Stereoselectivity at the beta2-adrenoceptor on macrophages is a major determinant
      of the anti-inflammatory effects of beta2-agonists.
AB  - Previous research has shown that beta-adrenoceptor (beta-AR) agonists have potent
      anti-inflammatory capabilities, e.g. represented by suppression of release of the
      proinflammatory cytokines. Aim of this research was to determine whether the
      effects of beta-agonists on LPS-induced TNFalpha and IL-10 release are influenced
      by their different stereochemistry. In addition, the role of the beta-AR subtypes
      was studied. The effect of two stereoisomers of the selective beta2-AR agonist
      TA2005 [(R,R)- and (S,S)-] on the LPS-induced TNFalpha and IL-10 release by U937
      macrophages was compared. The (R,R)-stereoisomer was 277 times more potent in
      inhibiting the TNFalpha release than the (S,S)-form. The (R,R)-stereoisomer also
      appeared to be more potent in increasing the IL-10 release. In radioligand
      binding studies the affinity of (R,R)-TA2005 for the beta-adrenoceptor was 755
      times higher than the (S,S)-TA2005 stereoisomer. In addition, the elevation of
      intracellular cAMP in U937 cells appeared to be stereoselective: (R,R)-TA2005 was
      more potent in elevating intracellular cAMP. The effect of both stereoisomers on
      the LPS-induced TNFalpha release could almost completely be antagonized by
      preincubation with the selective beta2-AR-antagonist ICI-118551. Further evidence
      that the effect of the beta-agonists is mediated via the beta2-adrenoceptor
      subtype exclusively was acquired by incubation of U937 cells with selective beta1
      and beta3-agonists. None of these receptor subtype agonists showed significant
      suppressive effect on TNFalpha release. This study provides additional proof that
      the anti-inflammatory effects of beta2-agonists are mediated via the beta2
      adrenoceptor and indicates that these effects are highly dependent on the
      stereoselectivity of the ligand.

PMID- 10961383
TI  - Critical role of P-selectin-dependent rolling in tumor necrosis factor-alpha
      induced leukocyte adhesion and extravascular recruitment in vivo.
AB  - Leukocyte-endothelium interactions are dependent on a coordinated expression and
      function of specific adhesion molecules. The objective of the present study was
      to examine the role of selectin function and leukocyte rolling in tumor necrosis
      factor-alpha (TNF-alpha)-induced leukocyte adhesion and extravasation in venules
      in vivo. For this purpose, we used intravital microscopy in the mouse cremaster
      muscle stimulated for 2-3 h with TNF-alpha intrascrotally. Pretreatment with
      fucoidan, which inhibits P- and L-selectin, and a P-selectin monoclonal antibody
      (RB40.34) abolished TNF-alpha-stimulated leukocyte rolling. This great reduction
      in rolling caused a marked attenuation of firm adhesion and extravascular
      accumulation of leukocytes. When fucoidan and RB40.34 were administrated after
      stimulation with TNF-alpha, it was found that leukocyte rolling was greatly
      reduced whereas the number of firmly adherent leukocytes was completely
      unchanged, suggesting that the inhibitory effect of blocking P-selectin function
      on firm leukocyte adhesion and recruitment was due to the reduction in leukocyte
      rolling along the endothelium. Moreover, pretreatment with a monoclonal antibody
      against intercellular adhesion molecule-1 (ICAM-1) and a platelet-activating
      factor (PAF)-receptor antagonist had no effect of TNF-alpha-induced leukocyte
      rolling and adhesion, indicating that molecules other than ICAM-1 and PAF mediate
      firm adhesion and recruitment of leukocytes in TNF-alpha-activated tissues. Taken
      together, our data demonstrate that P-selectin function plays an important role
      in TNF-alpha-induced inflammatory cell recruitment by mediating leukocyte rolling
      as a precondition for cytokine-provoked firm adhesion and transmigration in vivo.
      These findings, thus, suggest that inhibition of P-selectin may be a central
      target for pharmacological intervention in inflammatory diseases.

PMID- 10961384
TI  - Antinociception and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid antagonism by gabapentin in the rat spinal cord in vivo.
AB  - Gabapentin, a novel anticonvulsant and analgesic with an unknown mechanism of
      action, was tested on spinal dorsal horn neurone activity evoked by
      iontophoretically applied N-methyl-D-aspartic acid (NMDA) and (R,S)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and on nociceptive responses
      of single motor units (SMU) in anaesthetised rats. Gabapentin (10-215 mg/kg,
      i.v.) dose-dependently and selectively inhibited AMPA-evoked neuronal responses
      (ED50 106+/-24 mg/kg); no effect on NMDA-evoked activity was observed. In the
      same dose-range, gabapentin (10-215 mg/ kg, i.v.) dose-dependently reduced SMU
      responses to noxious electrical and mechanical stimulation. We conclude that
      gabapentin acts as an AMPA antagonist in the rat spinal cord, and that this
      mechanism is likely to substantially contribute to the antinociceptive effect of
      the drug.

PMID- 10961385
TI  - Immunocytochemical methods in haematology and oncology.
AB  - Immunocytochemical investigations of fixed cells are used to enhance diagnostic
      accuracy in haematology and oncology. The alkaline-phosphatase/anti(alkaline
      phosphatase) technique, immunoperoxidase and the avidin-biotin technique are the
      most important methods in immunocytochemistry. Tyramide-enhanced immunostaining
      is a new powerful technique. Peripheral blood smears and cytospins of mononuclear
      blood leucocytes have been analysed with this technique and these methods are
      also useful for analysis of bone marrow, cerebrospinal fluid, serous effusions
      and fine-needle aspirates. This review describes the results of
      immunocytochemistry in patients with B- and T-lymphoproliferative disorders,
      acute leukaemias and Hodgkin's disease. These methods are also useful for the
      detection of epithelial malignant cells. Immunocytochemistry supports the
      morphological analysis of cells in these disorders.

PMID- 10961386
TI  - The biology of multiple myeloma.
AB  - Multiple myeloma (MM) is a B-cell malignancy originating from pre-switched,
      follicle center B-lymphocytes which differentiate to plasma cells accumulating in
      the bone marrow. MM cells are characterized by a profound genetic instability
      resulting in a complex set of numerical and structural chromosomal abnormalities.
      Among these abnormalities, translocations involving 14q32, the immunoglobulin
      heavy-chain locus, are the most frequent aberrations, but translocation partners
      are remarkably heterogeneous. Chromosome 13q14 may harbor a critical tumor
      suppressor gene since MM patients with deletion of 13q14 experience short overall
      survival after conventional-dose and high-dose chemotherapy. Bone marrow stroma
      cells support growth and survival of MM cells, which in turn influence the bone
      marrow microenvironment. This is particularly evident by the markedly increased
      bone marrow vascularization observed in most patients with active MM.

PMID- 10961387
TI  - Effects of genistein and synergistic action in combination with eicosapentaenoic
      acid on the growth of breast cancer cell lines.
AB  - Genistein, a prominent isoflavone in soy products, produced dose- and time
      dependent in vitro growth inhibition at high concentrations (at least 185 microM)
      with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell
      lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line
      (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive
      MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells
      underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub
      G1 fraction in cell-cycle progression, and by a characteristic cell
      ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein,
      down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted
      in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human
      breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on
      MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary
      intake of genistein in combination with EPA may be beneficial for breast cancer
      control.

PMID- 10961388
TI  - Hydroxyurea induces a senescence-like change of K562 human erythroleukemia cell.
AB  - Hydroxyurea, a differentiation-inducing agent of human erythroleukemia K562
      cells, is commonly used to treat some types of leukemia. However, the mechanism
      for its therapeutic effect is not clearly understood yet. In this study, we have
      observed an interesting effect of hydroxyurea on tumor cells: an induction of
      senescence-like changes. Human erythroleukemia K562 cells, when treated with
      hydroxyurea for 7 days or more, underwent a change into phenotypically senescent
      cells together with a reduction of hemoglobin generation, a differentiation
      marker. The hydroxyurea-treated cells showed positive senescence associated-beta
      galactosidase staining, a senescence index, and the accumulation of cdk (cyclin
      dependent kinase) inhibitors, such as p16INK4a, p21Waf1, and p27Kip1, implicated
      in cellular senescence. Nonetheless, these changes were not accompanied by DNA
      fragmentation. Taken together, we summarize that the long-term treatment of
      cancer cells with hydroxyurea can induce cellular senescence different from
      differentiation or programmed cell death.

PMID- 10961389
TI  - Schedule dependent toxicity and efficacy of combined gemcitabine/paclitaxel
      treatment in mouse adenocarcinoma.
AB  - Increased interest in combining drugs with different targets has emerged over
      recent years. Our study aims at evaluating the effectiveness of combined
      gemcitabine/paclitaxel treatment taking into consideration doses, schedules, and
      toxicity. A spontaneous mammary carcinoma was transplanted into the right-hind
      foot of C3D2F1 mice. Paclitaxel (in doses from 20 to 80 mg/kg b.w.) and
      gemcitabine (in doses from 30 to 480 mg/kg b.w.) were administered i.p. in single
      or fractionated treatments. Toxicity and tumor growth delay (TGD) were the
      endpoints. TGDs for different gemcitabine doses in single administration (120,
      240, and 360 mg/kg) overlapped (TGD approximately = 2.5 days). Toxicity was very
      high in daily administration. Results with gemcitabine alone showed the efficacy
      of treatments every 3 days. TGDs in fractionated treatments of 60 and 120 mg/kg x
      4 were of approximately equals 16 days. Also in this case, tumor growth curves
      overlapped pointing out the uselessness of the high drug doses. For combined
      treatments, we used only fractionated protocols, administering gemcitabine every
      3 days. Paclitaxel was administered alone in one or two fractions and with
      different sequences in respect to gemcitabine administration. With 120 mg/kg of
      gemcitabine all the protocols showed an increased unacceptable toxicity. The best
      result was obtained administering paclitaxel 40 mg/kg on days 1 and 15 and
      gemcitabine 60 mg/kg on days 3, 6, 9, and 12 (TGD = 38.2 days). The light
      toxicity and the high efficacy obtained with this protocol indicate the possible
      use of gemcitabine/paclitaxel treatment in clinical practice.

PMID- 10961390
TI  - Increased angiogenin expression in gastric cancer correlated with cancer
      progression.
AB  - PURPOSE: The purpose of this study is to elucidate the expression of angiogenin
      and its previously undemonstrated clinical significance in gastric cancer (GC).
      METHODS: Angiogenin expression was examined immunohistochemically in 21 GC
      tissues and 21 corresponding normal gastric tissues. The serum concentration was
      determined by enzyme-linked immunosorbent assay (ELISA) in GC patients
      preoperatively (n = 48) and postoperatively (n = 41), in nonneoplastic patients
      preoperatively (n = 23) and postoperatively (n = 19), and in 32 healthy
      volunteers. The amount of angiogenin in the tissue of 21 GC patients was also
      determined by ELISA. RESULTS: Angiogenin expression was observed in GC cells as
      well as in some fundic glandular cells and some inflammatory cells. The mean
      serum concentration in GC patients (407.8 +/- 105.2 ng/ml) was significantly
      higher than that in the nonneoplastic patients (345.7 +/- 58.3 ng/ml; P < 0.003)
      and in the healthy volunteers (333.0 +/- 59.3 ng/ml; P < 0.0002). The mean serum
      angiogenin concentrations were progressively higher in the order T1 + T2 (P <
      0.04) < T3 + T4 (P < 0.0001) < recurrent GC (P < 0.05) subgroups, in the order
      node-negative (P < 0.05) < node-positive (P < 0.0002) subgroups, and in the order
      stage I +II (P < 0.02) < stage III and over (P < 0.0005) subgroups as compared
      with those in the healthy volunteers. These elevated serum angiogenin
      concentrations in each subgroup were significantly (P < 0.0003) reduced after
      cancer resection. The amounts of angiogenin in GC tissues correlated
      significantly with the serum angiogenin concentration (P < 0.01). CONCLUSIONS:
      These results suggest that angiogenin expression is increased in GC and that the
      increased serum concentration in GC patients correlates with cancer progression.

PMID- 10961391
TI  - Activity of extracranial metastases as a prognostic factor influencing survival
      after radiosurgery of brain metastases.
AB  - Information about prognostic factors influencing survival have been only
      occasionally reported in studies on the use of radiosurgery in the treatment of
      patients with brain metastasis. To answer the question of whether activity of
      extracranial metastases is an independent prognostic factor influencing survival
      in radiosurgery of brain metastases, a review of the literature was performed.
      Fourteen studies were identified in the English language literature that dealt
      with this topic. Only three studies showed borderline insignificance of the
      influence of activity of extracranial metastases when analysed by univariate
      methods. When multivariate analysis was used to test for the independent
      influence of this factor on survival, of nine studies that used that statistical
      approach eight showed that it is an independent prognosticator influencing
      survival, most often being the strongest one. This review of literature supports
      the view that the "activity of extracranial metastases" is an independent
      prognostic factor influencing survival of these patients as documented in
      published reports. However, prospective randomised trials are necessary to
      definitely establish the independent influence of this prognostic factor.

PMID- 10961392
TI  - Telomere shortening in gastric carcinoma with aging despite telomerase
      activation.
AB  - In the present study, we analyzed both telomere length and telomerase activity in
      surgical and autopsy samples of non-neoplastic mucosa and carcinomas of the
      stomach. Telomere length, determined by Southern blot analysis, demonstrated
      progressive shortening with age in non-neoplastic gastric mucosal specimens from
      38 human subjects aged between 0 and 99 years, with an average annual loss rate
      of 46 base pairs (bp). The mean (+/- SD) telomere length in 21 gastric carcinomas
      was 7.0 +/- 1.6 x 10(3) base pairs (1.6 kbp). In 20 (95%) of the 21 subjects, the
      values were smaller than those in the nonneoplastic gastric mucosa (mean
      shortening 1.8 kbp), although a strong correlation was observed for the paired
      data (r = 0.69, P = 0.0004). Similarly, telomere lengths in carcinomas were
      shorter than those for intestinal metaplasia (a mean difference of 1.1 kbp).
      Telomerase activity, estimated using the telomeric repeat amplification protocol
      assay, was positive in 18 (86%) of the 21 gastric carcinomas, without significant
      differences among the three histological types (well, moderately, and poorly
      differentiated adenocarcinomas) or with sex or age. The results suggest that
      telomere length and possibly shortening rates vary with the individual, and that
      examination of both non-neoplastic mucosa and tumors is necessary to improve our
      understanding of the significance of telomerase in neoplasia.

PMID- 10961393
TI  - Controlling the growth of polymer trees: concepts and perspectives for
      hyperbranched polymers.
AB  - This article summarizes basic principles and recent progress in the field of
      cascade-branched polymers. Methods for the preparation of macromolecules with
      hyperbranched structures are presented and compared concerning the extent of
      control over molecular weights and polydispersity. Step-growth and recently
      developed chain-growth strategies as well as enzyme and transition metal
      catalyzed polymerizations are discussed with respect to mechanism and future
      potential.

PMID- 10961394
TI  - Writing on the wall with a new synthetic quill
AB  - A new class of periodic mesoporous organosilicas (PMOs) with organic groups
      incorporated inside the channel walls of the material is discussed. In
      particular, the unique properties and chemistry exhibited by periodic mesoporous
      methylenesilica, an isoelectronic analogue of periodic mesoporous silica, are
      highlighted. Finally, some of the advances made in our group and others, as well
      as future directions that we envision in the field are described.

PMID- 10961395
TI  - Amination of aromatic olefins with anilines: a new domino synthesis of
      quinolines.
AB  - A new catalytic amination of aromatic olefins with anilines is presented. In a
      domino reaction, substituted quinoline derivatives are obtained in the presence
      of cationic rhodium complexes, such as [Rh(cod)2]BF4, and PPh3. Ethylbenzene is
      formed as a by-product in this new oxidative reaction. The first transition metal
      catalyzed anti-Markovnikov hydroamination of styrene with anilines occurs as a
      side reaction. Mechanistic investigations strongly support the regioselective
      oxidative amination of styrene as the key reaction step.

PMID- 10961396
TI  - Cyanide-bridge Fe-Fe and Fe-Co molecular squares: structures and electrochemistry
      of
AB  - Cyanide-bridged iron-iron and iron--cobalt molecular squares of [Fe(II/4)(mu
      CN)4(bpy)8[(PF6)4 x 4H2O (1), [Fe(II/2)Co(II/2)(mu-CN)4(bpy)8](PF6)4 x 3CHCl3 x
      2CH3CN (2), and [Fe(II/2)Co(III/2)(mu-CN)4(bpy)8](PF6)6 x 2CHCl3 x 4CH3NO2 (3)
      (bpy =2,2'-bipyridine) were prepared. X-ray structure analyses for 1-3 were
      performed and their electrochemistry was studied. In 1-3, four metal ions are
      bridged by cyanide groups to form tetranuclear macrocycles ("molecular squares").
      Each metal ion in the square is six-coordinate: four of the coordination sites
      are occupied by the nitrogen atoms of two of bpy ligands and the remaining cis
      coordination sites are occupied by cyanide-carbon or cyanide-nitrogen atoms. In
      1, Fe-C (cyanide) (1.899(4)-1.927(4)A) and Fe-N(cyanide) (1.929(4)-1.950(4)A)
      distances are typical of low-spin Fe2+ ions. In 2, Fe-C(cyanide) and Co(2+)
      N(cyanide) bond lengths are in the range 1.919(5)-1.963(5)A and 1.850(5)-2.017(5)
      A, respectively: in contrast, shorter bond lengths are observed for the metal to
      cyanide-carbon and cyanide-nitrogen (1.878(7)- 1.893(7) A) in 3. As a result, the
      molecular squares in 1. 2, and 3 have sides of 4.947(1)4.986(1) A, 5.001(1)
      5.053(1) A, and 4.910(1)-4.918(1) A, respectively. Magnetic susceptibility
      measurements revealed that the Fe2+ and Co3- ions in 1 and 3 are diamagnetic,
      while the high-spin Co2+ ions in 2 are weakly coupled through the low-spin Fe2
      ions. Cyclic voltammograms of the squares are presented, and the
      electrochemically generated mixed-valent species [Fe(II/2)Fe(III/2)(mu
      CN)4(bpy)8]6+ was discussed in terms of the intervalence transfer band.

PMID- 10961397
TI  - "NaB15": a new structural description based on X-ray and neutron diffraction,
      electron microscopy, and solid-state NMR spectroscopy
AB  - A boron-rich sodium boride, formerly known as NaB15, has been subjected to a
      comprehensive structural reinvestigation using X-ray single-crystal and powder
      diffraction, low-temperature neutron and electron diffraction, high-resolution
      transmission electron microscopy, and 23Na solid-state NMR spectroscopy. The
      results indicate that the previously published orthorhombic space group is
      incorrect. Consistent with all of the experimental results a modified structural
      description is developed in the monoclinic space group Ilml (a = 585.92(3), b=
      1039.92(6), c = 833.17(5) pin, beta = 90.373(5) from powder data). Because one of
      the interstitial boron atom positions remains unoccupied, the accurate
      compositional formula is NaB145 or Na2B29.

PMID- 10961398
TI  - Controlling the performance of silicalite-1 membranes
AB  - The structural and performance characteristics (for n- and i-butane separation)
      of self-supported silicalite-membranes, were optimised by fine-tuning their
      syntheses by screening a total of nine silica sources and many reaction
      conditions. The mass balances indicate that membrane thickness is a function of
      both the synthesis volume and the silica source used. The excellent properties of
      the final membrane are demonstrated by its high permselectivity of 31 for n
      butane combined with a n-butane flux of 10 mmol m(-2)s(-1), indicating perfect
      performance. For 50/50 mixtures (of n and i) the selectivity for nbutane was 48
      and its flux was 3.8 mmol m(-2)s(-1). For the given selectivities, in relation to
      the membrane thickness, the theoretical fluxes are the highest values ever
      reported, underlining the point that high structural integrity is essential to
      achieve superior functionality.

PMID- 10961399
TI  - Molecular batteries: ferrocenylsilylation of dendrons, dendritic cores, and
      dendrimers: new convergent and divergent routes to ferrocenyl dendrimers with
      stable redox activity
AB  - The ferrocenylsilylation of the phenol triallyl dendron 2, of the phenol
      nonaallyl dendron 4, and of the 9-, 27-, 81-, and 243-allyl dendrimers 7-10
      (monitored by the disappearance of the signals of the olefinic protons in 1H NMR
      spectra) has been achieved using ferrocenyldimethylsilane 1 and Karstedt's
      catalyst in diethyl ether at 40 degrees C, yielding the corresponding ferrocenyl
      dendrons and dendrimers. An alternative convergent synthesis of the
      nonaferrocenyl dendron 5 was carried out by reaction of the triferrocenyl dendron
      2 with a protected triododendron followed by deprotection. Reaction of the
      nonaferrocenyl dendron 5 with hexakis(bromomethyl)benzene gave the 54-ferrocenyl
      dendron 6. All the ferrocenyl dendron and dendrimers produce a chemically and
      electrochemically reversible ferrocenyl oxidation wave at seemingly the same
      potential. Stable platinum electrodes modified with the high ferrocenyl
      dendrimers were fabricated. The soluble orange-red ferrocenyl dendrimers can also
      be oxidized in CH2Cl2 by [NO][PF6] to the insoluble deep blue polyferrocenium
      dendrimers. For instance, the 243-ferrocenium dendrimer has been characterized by
      its Mossbauer spectrum, which is of the same type as that of ferrocenium itself.
      The ferrocenium dendrimers can be reduced without any decomposition back to the
      ferrocenyl dendrimer, indicating that these multielectronic redoxstable
      dendrimers behave as molecular batteries.

PMID- 10961400
TI  - Core modified meso-aryl corrole: first examples of CuII, NiII, CoII and RhI
      complexes.
AB  - A variety of metal complexes of 5,10,15-triphenyl-21-monooxa-corrole 4 have been
      investigated. This monooxa corrole, where one of the pyrrole ring is replaced by
      a furan moiety, is synthesized by the alpha-alpha coupling reaction of 16-oxa
      tripyrrane and dipyrromethane. The single crystal X-ray structure of 4 indicates
      only small deviation of the inner-core heteroatoms from planarity and this
      macrocycle arrange themselves into a columnar structure. Insertion of metals
      further flattens the corrole framework. Specifically, oxacorrole 4 binds to
      Nil(II), Cu(II), and Co(II) with the participation of all heteroatoms in the
      coordination. However, Rh(I) ion binds to only one imino and one amino nitrogen
      of the macrocycle. The bond angles at the metal center in the Ni(II) and Rh(I)
      complexes reveal square planar geometry completed by two CO molecules for Rh(I).
      The EPR spectra of the paramagnetic that Cu(II) and Col(II) complexes display
      significant decreases in the metal hyperfine couplings compared with the
      corresponding porphyrin complexes. The presence of superhyperfine coupling in the
      Cu(II) complex suggests delocalization of unpaired electron density into the
      ligand orbitals. Electrochemical studies reveal easier oxidations and harder
      reductions relative to the corresponding porphyrin derivatives while, the
      metallated derivatives did not show their characteristic metal reductions due to
      the high energy of their LUMO.

PMID- 10961401
TI  - A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4
      hydroxy-2(5H)-furanones from (S)-ketone cyanohydrins.
AB  - (S)-Ketone cyanohydrins (S)-2 are accessible by enantioselective HCN addition to
      ketones 1 by using hydroxynitrile lyase from Manihot esculenta ((S)-MeHNL) as a
      biocatalyst. Acylation of (S)-2 gave the corresponding (S)-acyloxynitriles (S)-3,
      which can be cyclized by LHMDS to give 5,5-disubstituted (S)-4-amino-2(5H)
      furanones (S)-4 and (S)-5. Different substituents (H. Me, OBn, OH) in the 3
      position of the furanones were introduced by selecting the appropriate acylating
      agent, which in the case of benzyloxyacetyl chloride led to the novel structure
      type of 4-amino-3-hydroxyfuranones (S)-5. For the synthesis of 5,5-disubstituted
      (S)-tetronic acids (S)-8, ketone cyanohydrins (S)-2 were first transformed into
      the corresponding 2-hydroxy esters (S)-6. Acylation of (S)-6 gave 2-acyloxy
      esters (S)-7, which, by treatment with LHMDS or LDA, afforded tetronic acids (S)
      8 in high yields and enantiomeric excesses. By debenzylation of benzyloxy acetoxy
      derivatives (S)-8e,f, the new vitamin C analogues (S)-9a,b were generated. All
      the described tetronic acid and aminofuranone derivatives were obtained in good
      chemical yields and without racemization with respect to the starting
      cyanohydrins (S)-2. In many cases the enantiomeric purity could be enriched by
      simple recrystallization (e.g. (S)-4a from 69% ee to > 99% ee).

PMID- 10961402
TI  - Ionization of ozone/chlorofluorocarbon mixtures in atmospheric gases: formation
      and remarkable dissociation of
AB  - The reactions occurring upon ionization of mixtures containing ozone and CHX2Y (X
      = H, Cl, F; Y = Cl, F) halocarbons diluted in atmospheric gases (O2, N2) have
      been investigated in detail by mass spectrometric and theoretical methods. In all
      systems investigated the reactivity pattern is characterized by the preliminary
      formation of [CHXY x O3+] adducts which undergo unimolecular dissociation into
      HXYO2+ and CO. This remarkable dissociation which requires extensive molecular
      reorganization is exceptional for hydrogenated halocarbons. The work represents
      the first systematic study of the ionic chemistry in systems containing both
      ozone and halocarbons diluted in atmospheric gases.

PMID- 10961403
TI  - Topological properties of the peptide bond in glycyl-L-threonine dihydrate based
      on a fast synchrotron/CCD-diffraction experiment at 100 K.
AB  - The charge density of glycyl-L-threonine dihydrate is extracted from a
      synchrotron data set of 98405 reflections collected at 100 K with a Bruker CCD
      area detector up to a resolution of d=0.38 A (sintheta/lambda = 1.32 A 1). The
      data are interpreted in terms of the "rigid pseudoatom" model. The topology of
      the experimental density is analyzed and compared with the topology obtained
      experimentally for the constituting amino acids and to that derived from Hartree
      Fock calculations for the isolated molecule. All critical points of the electron
      density at the covalent and hydrogen bonds, as well as those of the Laplacian,
      were located, thereby deriving quantitative topological data for the peptide and
      side chain bonds. Bond topological indices in the dipeptide compare well with
      those of the corresponding bonds in the building amino acids, thus suggesting
      transferability of electronic properties of atoms and functional groups when
      these are derived by Bader's partitioning. Discrepancies between theoretical and
      experimental results could be attributed to crystal field effects.

PMID- 10961404
TI  - The role of the alpha-stereogenic center in the control of stereoselection in the
      reduction of alpha-alkyl-beta-hydroxy ketones: a highly diastereoselective
      protocol for the synthesis of 1,2-syn-2-alkyl-1,3-diols
AB  - Accurate investigations on the role played by an alpha-stereogenic center in
      controlling the reduction of various classes of beta-hydroxy ketones allowed us
      to set up a general and highly diastereoselective protocol for the synthesis of 2
      alkyl-1,3-diols with 1,2-syn relationship. This methodology is based on the
      conversion of a beta-hydroxy ketone into the corresponding titanium alcoholate
      that permits us to organize the substrate in a stable and rigid structure, which
      stereofacially favors attacking hydride ions. The use of THF as solvent makes
      available a variety of hydride donors that cover a large spectrum of steric
      demand: the choice of the more appropriate one depends on the conformational
      stability of the cyclic intermediate. Excellent results are obtained also in the
      presence of an additional stereogenic center in the beta-position, even if it
      exerts a concordant or an opposite steric effect with respect to the alpha
      substituent.

PMID- 10961405
TI  - Azo-azulene derivatives as second-order nonlinear optical chromophores
AB  - The molecular and solid state nonlinear optical (NLO) properties of several
      (phenylazo)-azulenes are investigated. In particular, (4-nitrophenylazo)-azulene
      (2b) exhibits a quadratic hyperpolarizability (beta(vec)) of 80 x 10(-30) cm5esu
      recorded at 1.907 microm by the electric field-induced second-harmonic (EFISH)
      technique. This molecular material, which crystallizes in the monoclinic
      noncentrosymmetric space group Pc, exhibits an efficiency 420 times that of urea
      in second-harmonic generation. The origin of the optical nonlinearity in azo
      azulene is discussed in relation with crystal structures and semiempirical
      calculations within the INDO/SOS formalism, and compared with that of the well
      known disperse red one (DR1) organic dye.

PMID- 10961407
TI  - Violene/cyanine hybrids as electrochromics part 2: tetrakis(4
      dimethylaminophenyl)ethene and its derivatives
AB  - The general structure of violene/cyanine hybrids (see below) is exemplified by
      tetrakis(4-dimethylaminophenyl)ethene 1(RED) its vinylogue 2(RED) and its
      diazavinylogue 3(RED). As judged from their cyclic voltammograms and
      spectroelectrograms, oxidation occurs perfectly reversible by loss of two
      electrons creating closed shell systems 1-3(OX)+2 with strong bathochromic shifts
      (Michlers hydrol blue moieties). ESR spectra indicate only minor amounts of
      radical cations. At much higher potentials by another reversible loss of two
      electrons (-->1-3(OX)+4) the long wavelengths absorptions are replaced by shorter
      ones. In system 4, containing two 4-dimethylaminophenyl units only, the violene
      character is better preserved since oxidation occurs stepwise by single electron
      transfer up to 4(OX)+4. These results are backed by theoretical calculations for
      1-4, demonstrating the strong geometrical differences between the various
      oxidation levels. Besides, new types of cyclic structures for 1-4(OX)+4 are
      indicated by these calculations: For systems 1-3 cyclic structures for
      tetracations have been found to be more stable by 3-20 kcalmol(-1) than acyclic
      structures, whereas for system 4 the acyclic structure is more stable by about 22
      kcalmol(-1). The redox behavior of systems 1-4 is of general importance for
      electrochromic systems.

PMID- 10961406
TI  - Non-covalent conjugates between cationic polyamino acids and GdIII chelates: a
      route for seeking accumulation of MRI-contrast agents at tumor targeting sites.
AB  - Three novel Gd chelates containing on their external surface pendant phosphonate
      and carboxylate groups, which promote the interaction with the positively charged
      groups of polyornithine and polyarginine, have been synthesized. Their solution
      structures have been assessed on the basis of 1H- and 31P-NMR spectra of the Eu
      and Yb analogues. A thorough investigation of the relaxometric (1H and 17O)
      properties of the Gd chelates has been carried out and the observed relaxivities
      have been accounted for the sum of three contributions arising from water
      molecules in the first, second, and outer coordination layers, respectively. It
      has been found that the occurrence of a tight second coordination coating renders
      the dissociation of the water molecule directly coordinated to the Gd ion more
      difficult. The binding interactions between the negatively charged Gd chelates
      and the positively charged groups of polyornithine (ca. 140 residues) and
      polyarginine (ca. 204 residues) have been evaluated by means of the proton
      relaxation enhancement (PRE) method. Although the binding interaction decreases
      markedly in the presence of competitive anions in the solution medium, the
      affinity is strong enough that in blood serum it is possible to meet the
      conditions where most of the chelate is bound to the polyamino acid substrate. On
      this basis one may envisage a novel route for a MRI location of tumors as it is
      known that positively charged polyamino acids selectively bind to tumors having a
      greater negative charge than non-tumor cells.

PMID- 10961408
TI  - Geminal bis-ureas as gelators for organic solvents: gelation properties and
      structural studies in solution and in the gel state
AB  - Several geminal bis-urea compounds were synthesised by means of an acid-catalysed
      condensation of various benzaldehydes with different monoalkylureas. Many of
      these compounds form thermoreversible gels with a number of organic solvents at
      very low concentrations (<3mM) and which are stable to temperatures higher than
      100 degrees C. Electron microscopy revealed a three-dimensional (3D) network of
      intertwined fibres, which are several tens of micrometers long and have a width
      ranging from approximately 30 to 300 nm. The possible aggregate forms and
      aggregate symmetries were evaluated by means of molecular mechanics calculations.
      1H NMR, 2D NMR, 13C NMR and 13C-CP/MAS NMR techniques were used to obtain
      information about the aggregation and possible aggregate symmetry of geminal bis
      ureas in solution, in the gel state, and in the solid state.

PMID- 10961410
TI  - Fine-tuning of metallaborane geometries: chemistry of iridaboranes derived from
      the reaction of
AB  - From reaction of [(Cp*Ir)2HxCl(4-x)] (x=1, 0) and LiBH4, arachno
      [[Cp*IrH2]B3H7](1) is produced in moderate yield concurrently with [Cp*IrH4]. In
      contrast, reaction of [(Cp*Ir)2H2Cl2] with LiBH4 results in arachno-[[Cp*IrH]2(mu
      H)B2H5] (3) in high yield at room temperature but a mixture of 1 and
      [[Cp*IrH]2(mu-H)BH4] (2) at 0 degrees C. BH3 x THF converts 1 to arachno
      [(Cp*IrHB4H9] (4) and 2 to 3 with 1 as a minor product. Further, reaction of 3
      with excess of BH3 x THF results in formation of nido-[[Cp*Ir]2-(mu-H)B4H7] (6)
      formed by loss of H2 from the intermediate arachno-[[Cp*IrH]2B4H8] (5). Reaction
      of 1 with [Co2(CO)8] permits the isolation of two metallaboranes, arachno
      [[Cp*Ir(CO)]-B3H7] (7) and nido-[1-[Cp*Ir]-2,3-Co2-(CO)4(mu-CO)B3H7] (8).
      Treatment of 4 with [Co2(CO)8] gives only one single mixed-metal metallaborane
      nido-[1-[Cp*Ir]-2-Co(CO)3B4H7 (9) in high yield. Finally, pyrolysis of 8 results
      in loss of hydrogen and formation of pileo-[1-[Cp*Ir]-2,3-Co2(CO)5B3H5] (10) with
      a BH-capped square-pyramidal structure. With kinetic control rational synthesis
      of a variety metallaboranes has been achieved by varying the number of chlorides
      in the monocyclopentadienylmetal halide dimer, reaction temperature, types of
      monoborane, and metal fragment sources.

PMID- 10961409
TI  - Theoretical and experimental study of the acetohydroxamic acid protonation: the
      solvent effect.
AB  - The mechanism of the protonation of acetohydroxamic acid is investigated
      comparing experimental results and ab initio calculations. Experimentally, the UV
      spectral curves were recorded at different temperatures, at constant
      dioxane/water concentration, and at very high concentrations of strong mineral
      acids. The process is followed by monitoring the changes in the UV curves with
      increasing acid concentration. The molecular structures and the solvation
      energies were calculated with the RHF, B3LYP, and MP2 methods. The solvent is
      treated as a continuum of uniform dielectric constant. The isolated molecule of
      acetohydroxamic acid exhibits two protonation sites, the carbonyl oxygen and the
      nitrogen atom. In dioxane/water mixture, the RHF calculations predict the
      existence of a third cation of low stability, where the proton is bonded to the
      OH oxygen. With the MP2 ab initio calculations, the free energies of the
      formation processes in solution of the two most stable cations, CH3COH-NHOH+
      (O3H+) and CH3CO-NH2OH+ have been evaluated to be -160.2 kcalmol(-1) and -157.6
      kcal mol(-1). The carbonyl site is the most active center in solution and in the
      gas phase. The carbonyl site is also the most active center in the UV
      measurements. Experimentally, the ionization constant was found to be pK(O3H+) = 
      2.21 at 298.15 K, after the elimination of the medium effects using the Cox-Yates
      equation for hight acidity levels. Experiments and ab initio calculations
      indicate that K(O3H+) decreases with the temperature.

PMID- 10961411
TI  - White matter changes: the clinical consequences in the aging population.
AB  - Neuroimaging changes in the cerebral subcortical white matter (WMC) are
      recognized with the highest frequency in elderly subjects, particularly in those
      with vascular risk factors. WMC have been consistently reported to be associated
      with global or selective cognitive deficits, depression, motor and gait
      impairment. All these deficits are main contributors to disability in the
      elderly. Moreover, subjects with WMC have an increased risk of cardiovascular
      events and death from vascular causes. Functional status in subjects with WMC is
      variable, from normal to severely (physically or cognitively) disable. The
      association of WMC with age and with some of the clinical manifestations of aging
      suggests that WMC could be one of the age-related processes involved in the
      transition to disability in the elderly. Large cohorts of patients with WMC of
      different severity and detailed follow-up observation may help elucidating this
      issue. If WMC are shown to have an impact on disability in the aged population,
      efforts could be made to prevent WMC and WMC-related motor and cognitive
      deficits, and to identify measures aimed to halt or slow their progression.

PMID- 10961412
TI  - Longitudinal change of white matter abnormalities.
AB  - A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the
      Austrian Stroke Prevention Study provides first information on the rate, clinical
      predictors, and cognitive consequences of MRI white matter hyperintensity in
      elderly individuals without neuropsychiatric disease. Lesion progression was
      found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked
      in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) and
      early confluent or confluent white matter hyperintensities at baseline (odds
      ratio 2.62) were the only significant predictors of white matter hyperintensity
      progression. Lesion progression had no influence on the course of
      neuropsychologic test performance over the observational period.

PMID- 10961413
TI  - Genetic aspects of microangiopathy-related cerebral damage.
AB  - Microangiopathy related cerebral damage (MARCD) includes early confluent and
      confluent white matter hyperintensities (WMH) and lacunar lesions. It is expected
      to be the result of interactions between multiple genetic and environmental
      factors. The estimated proportion of genetic factors contributing to the
      interindividual variation seen in WMH volume is 73%. This estimate points to a
      significant genetic component in WMH development. In the setting of the Austrian
      Stroke Prevention Study we search for genes being associated with the presence,
      severity and progression of MARCD using the candidate gene approach. Defining
      susceptibility genes may allow to better identify individuals at high risk for
      MARCD and to target preventive measures.

PMID- 10961414
TI  - Research criteria for subcortical vascular dementia in clinical trials.
AB  - Vascular dementia (VaD) incorporate different vascular mechanisms and changes in
      the brain, and have different causes and clinical manifestations. Variation in
      defining the cognitive syndrome, in vascular etiologies, and allowable brain
      changes in current clinical definitions of VaD have resulted in variable
      estimates of prevalence, of groups of subjects, and of the types and distribution
      of putative causal brain lesions. Thus current criteria for VaD select an
      etiologically and clinically heterogeneous group. This definitional heterogeneity
      may have been a factor in "negative" clinical trials. An alternative for clinical
      drug trials is to focus on a more homogeneous group, such as those with
      subcortical (ischemic) VaD. This designation incorporates two small vessel
      clinical entities "Binswanger's disease" and "the lacunar state". It comprises
      small vessel disease as the primary vascular etiology, lacunar infarct(s) and
      ischaemic white matter lesions as the primary type of brain lesions, and
      subcortical location as the primary location of lesions. The subcortical clinical
      syndrome is the primary clinical manifestation, a definition which still requires
      additional empirical data. We expect that subcortical VaD show a more predictable
      clinical picture, natural history, outcome, and treatment responses. We propose a
      modification of the NINDS-AIREN criteria as a new research criteria for
      subcortical VaD.

PMID- 10961415
TI  - How can cerebral infarcts and hemorrhages lead to dementia?
AB  - The incidence of new onset dementias is increased after stroke. The objective of
      this review is to investigate how cerebral infarcts and hemorrhages can lead to
      dementia. Stroke subtypes, total volume of cerebral lesion and functional tissue
      loss, and location of the lesions are the major determinant of dementia in stroke
      patients. The causal relationship between stroke and dementia is clear: (1) in
      young patients who are unlikely to have associated Alzheimer pathology; (2) when
      the cognitive functioning was normal before stroke, impaired immediately after,
      and does not worsen over time; (3) when the lesions are located in strategic
      areas; and (4) when a well-defined vasculopathy known to be associated with
      dementia is proven. However, white matter changes and associated Alzheimer
      pathology may also contribute to the dementia syndrome in stroke patients.

PMID- 10961416
TI  - Vascular aspects in Alzheimer's disease.
AB  - Alzheimer's disease is a primary degenerative dementia and is not considered to
      be of vascular origin. Furthermore, severe cerebrovascular diseases are generally
      exclusionary for the clinical diagnosis. During recent years both epidemiological
      and neuropathological studies have suggested an association between Alzheimer's
      disease and several vascular risk factors, such as hypertension, inheritance of
      the apolipoprotein E epsilon4 allele, coronary heart disease, diabetes mellitus,
      ischaemic white matter lesions and generalised atherosclerosis. These findings
      may reflect an overdiagnosis of Alzheimer's disease in individuals with silent
      cerebrovascular disease or that cerebrovascular disease may affects the clinical
      expression of Alzheimer's disease. Further possibilities include that Alzheimer's
      disease may increase the risk of vascular disease or that vascular disease may
      stimulate the Alzheimer's disease process. Similar mechanisms may also be
      involved in the pathogenesis of both disorders, such as disturbances in the renin
      angiotensin system, apoptosis, and psychological stress.

PMID- 10961417
TI  - Novel imaging technologies in the assessment of cerebral ageing and vascular
      dementia.
AB  - Introduction of magnetic resonance imaging (MRI) has opened new possibilities for
      detecting age-related brain tissue changes. The majority of these abnormalities
      consists of hyperintense foci in the deep and subcortical white matter probably
      related to microvascular disturbances and of signal hyperintensities around the
      lateral ventricles. It has also been suggested that these abnormalities may
      contribute to the development of cognitive impairment. The correlation between
      age-related signal abnormalities on conventional MRI and neuropsychologic
      dysfunction is limited, however, and a threshold beyond which such a relation may
      come into existence has not yet been defined. Poor tissue characterisation by
      conventional MRI may be one explanation. Therefore, new pulse sequences are
      expected not only to provide a higher lesion contrast such as the fluid
      attenuated inversion recovery (FLAIR) technique but also to offer new insights
      concerning the composition of incidental brain lesions. In this context both
      magnetisation transfer imaging (MTI) and diffusion weighted imaging (DWI) may
      serve to gain information about the integrity of cell membranes and organelles
      and the preservation of axons and fibre tracts. We will review the technical
      background of these recently developed MR sequences and their first applications
      to age-associated brain abnormalities.

PMID- 10961418
TI  - Alzheimer disease and neuroinflammation.
AB  - It is now generally accepted that the lesions of Alzheimer disease (AD) are
      associated with a host of inflammatory molecules, including complement proteins,
      as well as with many activated microglia. Most inflammatory components are
      synthesized by brain cells. In order to estimate the intensity of the
      inflammatory reaction, we have measured the levels of the mRNAs for complement
      proteins, two complement regulators (CD59 and C1 inhibitors), an acute phase
      reactant (C-reactive protein, CRP) and two microglial markers, (HLA-DR and
      CD11b), in normal and AD brain. The mRNAs for inflammatory mediators are markedly
      upregulated in AD tissue while those of the complement inhibitors are almost
      unchanged. The upregulations for CRP and CD11b in AD hippocampus are comparable
      to those in osteoarthritic joints. This lends further support to the hypothesis
      that chronic inflammation may be causing neuronal death in AD.

PMID- 10961419
TI  - The immunological microenvironment in the CNS: implications on neuronal cell
      death and survival.
AB  - Microenvironmental factors have a profound influence on resident cell populations
      and their ability to modulate an immune response. The unique central nervous
      system (CNS) microenvironment has important effects in this regard, resulting in
      the establishment of immune privilege. The immune response in the CNS is under
      tight control of bipolar regulatory mechanisms. Neurons have a suppressive
      potential, which prevents and limits the formation of inflammatory responses. In
      contrast, activated lymphocytes, which can invade the CNS, deposit potentially
      pro-inflammatory mediators. The balance between pro- and anti-inflammatory
      factors determines localization, intensity and course of immune responses in the
      brain. Thus, an overwhelming invasion of activated lymphocytes, which may have
      emerged from a recent anti-microbial immune response, may create inflammation in
      intact parts of the CNS. In contrast, in compromised brain areas, much weaker
      proinflammatory forces are required to create the same effect. Thus, in
      degenerative brain lesions, inflammatory infiltrates may be formed easily. Immune
      cell invasion and expression of immune effector molecules in degenerative CNS
      disease could exert a variety of actions on the neurons. In the first instance,
      activation of the local immune response could be harmful to resident brain cells,
      possibly resulting in neuronal cell death. Alternatively, immune cell-derived
      mediators could protect and support the regeneration of damaged neurons.
      Recently, it has been realized that normal inflammatory cells (lymphocytes and
      macrophages) produce neurotrophic factors. In addition, pro-inflammatory
      cytokines released by invading immune cells may have a role in neuroprotection.
      Infiltration of degenerative brain areas by inflammatory cells could thus reflect
      a beneficial process encouraging neuronal survival and local cell regeneration.

PMID- 10961420
TI  - Toxic effector molecules in the pathogenesis of immune-mediated disorders of the
      central nervous system.
AB  - A growing body of evidence supports the notion that inflammatory reactions in the
      central nervous system (CNS) are not only restricted to established immune
      mediated disorders, such as multiple sclerosis, but also contribute to the
      pathogenesis of Alzheimer's disease and other types of neurodegenerative
      disorders. The biological roles of toxic mediators, such as nitric oxide,
      reactive oxygen species, as well as complement and proteases in the genesis of
      inflammatory reactions in the CNS are reviewed within the context of
      demyelination and neuronal damage.

PMID- 10961421
TI  - Cytokines in CNS disorders: neurotoxicity versus neuroprotection.
AB  - Cytokines orchestrate T cell-mediated immune responses. In experimental
      autoimmune encephalomyelitis (EAE) the proinflammatory cytokines interferon (IFN)
      gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-12 and
      IL-18 are critically involved in the initiation and amplification of the local
      immune response in the CNS which is counter-balanced by upregulation of
      antiinflammatory cytokines such as IL-10. The predicted function of individual
      cytokines during EAE has recently been challenged by transgenic animal studies
      and neutralization experiments. Cytokine induction is not restricted to
      autoimmunity in the nervous system. Cytokines are involved in nerve regeneration
      and induced in focal cerebral ischemia both at the site of infarction and in
      remote nonischemic brain regions. In cerebral ischemia TNF-alpha and IL-1beta
      probably have dual functions: In concert with upregulation of inducible NO
      synthase (iNOS) they exert neurotoxicity while in the absence of iNOS, TNF-alpha
      and IL-1beta may contribute to neuroprotection and plasticity. The interplay
      between glial cells, infiltrating leukocytes and induced cytokines leading to CNS
      pathology is complex and incompletely understood. Further assessment of the
      functional contribution of cytokines critically depends on the elucidation of
      downstream secondary signaling mechanisms.

PMID- 10961422
TI  - Do neuronal inclusions kill the cell?
AB  - Neurofibrillary tangles, Pick bodies and Lewy bodies are considered
      quantitatively in relation to neuron loss. It would seem that the inclusions are
      not themselves the cause of neuron death.

PMID- 10961423
TI  - Mechanisms of cell death in neurodegenerative disorders.
AB  - OBJECTIVE: Progressive cell loss in specific neuronal populations is the
      prominent pathological hallmark of neurodegenerative diseases, but its molecular
      basis remains unresolved. Apoptotic cell death has been implicated as a general
      mechanism in Alzheimer disease (AD) and other neurodegenerative disorders.
      However, DNA fragmention in neurons is too frequent to account for the continuous
      loss in these slowly progressive diseases. MATERIAL AND METHODS: In 9 cases of
      morphologically confirmed AD (CERAD criteria, Braak stages 5 or 6), 5 cases of
      Parkinson disease (PD) and 3 cases each of Dementia with Lewy bodies (DLB),
      Progressive Supranuclear Palsy (PSP), and Multiple System Atrophy (MSA), and 7
      age-matched controls, the TUNEL method was used to detect DNA fragmentation, and
      immunohistochemistry for an array of apoptosis-related proteins (ARP),
      protooncogenes, and activated caspase-3 were performed. RESULTS: In AD, a
      considerable number of hippocampal neurons showed DNA fragmentation with a 3 to
      5.7 fold increase related to neurofibrillary tangles and amyloid deposits, but
      only exceptional neurons displayed apoptotic morphology (1 in 1100-5000) and
      cytoplasmic immunoreactivity for ARPs and activated caspase-3 (1 in 2600 to 5650
      hippocampal neurons), whereas no neurons were labeled in age-matched controls.
      Caspase-3 immunoreactivity was seen in granules of granulovacuolar degeneration,
      only rarely colocalized with tau-immunoreactivity. In PD, DLB, and MSA, TUNEL
      positivity and expression of ARPs or activated caspase-3 was only seen in
      microglia, rare astrocytes and in oligodendroglia with cytoplasmic inclusions in
      MSA, but not in nigral or other neurons with or without Lewy bodies. In PSP, only
      single neurons but oligodendrocytes, some with tau deposits, in brainstem
      tegmentum and pontine nuclei were TUNEL-positive and expressed both ARPs and
      activated caspase-3. CONCLUSIONS: These data provide evidence for extremely rare
      apoptotic neuronal death in AD compatible with the progression of neuronal
      degeneration in this chronic disease. In other neurodegenerative disorders,
      apoptosis mainly involves microglia and oligodendroglia, while alternative
      mechanisms of neuronal death may occur. Susceptible cell populations in a
      proapoptotic environment show increased vulnerability towards metabolic and other
      pathogenic factors, with autophagy as a possible protective mechanism in early
      stages of programmed cell death. The intracellular cascade leading to cell death
      still awaits elucidation.

PMID- 10961424
TI  - Estrogens, apoptosis and cells of neural origin.
AB  - In view of the relevant complexity of estradiol actions in the nervous system, we
      have proposed to utilize a reductionist approach and gain an insight on its role
      in neural cells via the identification of the genes target for this hormone. Once
      obtained a biochemical footprint of the responses elicited by E2 in the neural
      target cells we believe that the physiological effects exerted by this hormone
      will be more easily elucidated; in addition, we might find novel targets for
      drugs aimed at mimicking or blocking E2 effects. We here summarize preliminary
      results obtained in the cell line SK-ER3 appropriately engineered by us to
      express the ERalpha. We show that nip-2, one of the genes found to be regulated
      by E2, is involved in the mechanisms leading to cell death. This finding led us
      to investigate on estrogen effects on SK-ER3 apoptosis. We found that E2 has a
      significant anti-apoptotic activity in SKER3 cells. These results are in line
      with the recent reports from other laboratories indicating that E2 may prevent
      death of neural cells exposed to toxic stimuli. We conclude that these initial
      studies seem to support the strategy of our research and underline the strength
      of inverse genetics in the study of the physiology of sex hormone activities.

PMID- 10961425
TI  - Markers of apoptosis and models of programmed cell death in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is neuropathologically marked by the presence of senile
      plaques composed of beta-amyloid peptide and by neurofibrillary tangles formed by
      abnormally phosphorylated tau protein. Many authors have also reported a neuronal
      loss in affected regions of the brain in AD patients. This neuronal degeneration
      could be linked to the triggering of intracellular pathways leading to apoptosis.
      Previous works were focused on the links between neuronal apoptosis and tau and
      amyloid precursor protein (APP) metabolisms. We have analyzed tau gene expression
      in primary neuronal cultures submitted to an apoptotic stress produced by
      excitotoxicity or serum deprivation. Glutamate induces an enhancement of tau gene
      expression in resistant neurons whereas a reduced expression is noted in
      apoptotic cells. This decrease is similar to what is observed after trophic
      support withdrawal in neuronal cultures. Neurons expressing phosphorylated tau
      are more resistant to experimental apoptosis than neurons positively labeled for
      dephosphorylated tau protein (AT8/Tau 1 epitope). In vitro apoptotic neurons are
      able to produce membrane blebbings (strongly immunopositive for APP and
      amyloidogenic fragments) that are secondary released in the extracellular space.
      Finally neurons overexpressing human mutated presenilin 1 (M146 L) are more prone
      to degenerate than neurons overexpressing human wild-type presenilin 1 after
      apoptosis induction.

PMID- 10961426
TI  - Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative
      disease.
AB  - A major risk factor for neurodegenerative diseases such as Parkinson's disease
      (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Alzheimer's
      disease (AD) and progressive supranuclear palsy (PSP) is aging. Two processes
      that have been implicated in aging are free radical-induced oxidative damage and
      mitochondrial dysfunction. A progressive impairment of mitochondrial function
      and/or increased oxidative damage has been suggested to play critical roles in
      the pathogenesis of these neurodegenerative diseases. For example, decreased
      complex I activity, increased oxidative damage and altered activities of
      antioxidant defense enzymes have been demonstrated in PD. In AD, decrements in
      complex IV activity and increased oxidative damage have been reported. Reductions
      in complex II activity, increased cortical lactate levels and oxidative damage
      have been described in HD. Some familial ALS cases are associated with mutations
      in the gene for Cu,Zn superoxide dismutase (SOD1) while increased oxidative
      damage is observed in sporadic ALS. Studies in PSP have demonstrated regionally
      specific reductions in brain and muscle mitochondrial function, hypofrontality
      and increased oxidative damage. Altogether, the age-dependent onset and
      progressive course of these neurodegenerative diseases may ultimately highlight
      an association between aging, mitochondrial impairment and oxidative stress.

PMID- 10961427
TI  - Genetics of Alzheimer's disease--routes to the pathophysiology.
AB  - Considerable advances have been made the last years in the understanding of the
      pathogenesis of Alzheimer's disease (AD): Several pathogenic mutations have been
      found in the amyloid precursor protein gene on chromosome 21. Two other
      dominantly operating genes on chromosome 14 and 1 were recently cloned, named
      presenilin 1 and 2, respectively. Mutations in these genes give rise to AD with a
      very early age of onset. Increased Abeta1-42 is most likely the pathogenic
      mechanism in all these cases. A susceptibility gene for AD has also been found.
      There is an association between the epsilon4 allele of the apolipoprotein E
      (APOE) gene and late-onset AD. The epsilon4 allele increases the risk for AD,
      although some epsilon4 homozygotes may live a long life without developing AD.
      The mechanism by which APOE epsilon4 promotes development of AD is most likely
      increased plaque formation. The new knowledge on pathogenic mechanisms of the
      disease gives opportunities for alternative strategies for therapeutic
      intervention.

PMID- 10961428
TI  - Secretion of the amyloid precursor protein is elevated isoform specifically by
      apolipoprotein E4.
AB  - Genetic studies suggest that the neuropathology and etiology of Alzheimer's
      disease (AD) are associated with several genotypes including mutations in the
      amyloid precursor protein (APP) gene and the allele E4 of apolipoprotein E
      (apoE). The present study investigated the possibility that cross talk
      interactions exist between APP and apoE and the extent to which they are affected
      by the apoE genotype. This was pursued by cell culture and immunoblot experiments
      utilizing neuroblastoma N2a cells in which the effects of distinct apoE isoforms
      on the levels of intracellular APP and of secreted APPs were determined. This
      revealed that treatment of the cells with apoE4, the AD risk factor, resulted in
      a marked increase in the levels of secreted APPs. This effect was dose dependent
      (ED50 approximately/= 2.5 microg/ml) and isoform specific in that apoE3 had
      virtually no effect on the secretion of APPs.

PMID- 10961429
TI  - Alterations in neurotrophins and neurotrophin receptors in Alzheimer's disease.
AB  - We demonstrated that nerve growth factor (NGF) levels were increased in
      hippocampus and cortical areas, as well as in cerebrospinal fluid (CSF) of
      patients with Alzheimer's disease (AD). Such increases may, at least in part, be
      due to a decreased expression of the NGF high affinity receptor trkA. Measurement
      of CSF levels of NGF may add to the repertoire of potential biochemical
      diagnostic markers in living AD patients.

PMID- 10961430
TI  - Genetically altered transgenic models of Alzheimer's disease.
AB  - Abnormal processing and aggregation of synaptic proteins might play an important
      role in the pathogenesis of neurodegenerative disorders. Among them, amyloid
      precursor protein (APP) has been clearly associated with Alzheimer's disease (AD)
      and various transgenic (tg) animal models have been developed where mutant APP is
      overexpressed under the regulatory control of neuronal promoters. These studies
      have shown that AD-like pathology (namely plaques and synapse damage) begins to
      develop at 6-8 months of age in mice expressing human APP under Thy1, platelet
      derived growth factor (B-chain) or protease-resistant prion protein promoters,
      provided that levels of APP are higher than 5-7 fold of endogenous levels. None
      of these models have shown the presence of tangles; however, tau-immunoreactive
      neurites in plaques and astroglial/microglial activation are observed after 12
      months of age. Neuronal loss and alterations of synaptic function and
      connectivity are found in the CA1 region in the PDAPP tg mice lacking the Swiss
      Webster background. Co-expression of other genes associated with AD modify this
      phenotype, for example, mutant presenilin 1 accelerates the onset of plaque
      formation, transforming growth factor beta enhances vascular amyloidosis, and
      apolipoprotein E decreases amyloid deposition. In conclusion, tg mice which are
      capable of mimicking some aspects of AD (provided that high enough levels of
      expression are achieved) can potentially be used to test novel drugs for the
      treatment of neurodegenerative disorders.

PMID- 10961431
TI  - Morphological substrates of mental dysfunction in Lewy body disease: an update.
AB  - Mental dysfunction including cognitive, behavioural changes, mood disorders, and
      psychosis are increasingly recognized in patients with Parkinson's disease (PD)
      and related disorders. Their morphological correlates are complex due to multiple
      system degeneration. CNS changes contributing to cognitive changes in PD include
      1. Dysfunction of subcorticocortical networks with neuron losses in a) the
      dopaminergic nigrostriatal loop, causing striato-(pre)frontal deafferentation and
      mesocortico-limbic system (medial substantia nigra, ventral tegmentum); b)
      noradrenergic (locus coeruleus), and serotonergic systems (dorsal raphe nuclei),
      c) cholinergic forebrain system (nucleus basalis of Meynert, etc), and d)
      specific nuclei of amygdala and limbic system (thalamic nuclei, hippocampus); 2.
      Limbic and/or cortical Lewy body and Alzheimer type pathologies with loss of
      neurons and synapses, 3. Combination of subcortical, cortical, and other
      pathologies. In general, degeneration of subcortical and striato-frontal networks
      causes cognitive, executive, behavioural, and mood disorders but less severe
      dementia than cortical changes which, when present in sufficient numbers, are
      important factors for overt dementia. In PD, cortical tau pathology with similar
      or differential patterns than in Alzheimer disease (AD) shows significant linear
      correlation with cognitive decline. In dementia with Lewy bodies (DLB), the
      second most frequent cause of dementia in the elderly, cortical Lewy bodies (LB)
      may or may not be associated with amyloid plaques and neuritic AD lesions. They
      predominantly affect the limbic system with less frequent isocortical Braak
      stages, whereas the cholinergic forebrain system is more severely affected than
      in AD. Both neuritic degeneration in limbic system in PD and DLB and the density
      of cortical synapse markers correlate with neuritic AD pathology and less with
      cortical LB counts. Apolipoprotein E epsilon4 allele frequency may represent a
      common genetic background for both AD and LB pathologies but there are different
      proportions of plaques between DLB (less Abeta1-40) and AD (more frequent Abeta1
      40). Familial parkinsonism with dementia, linked to chromosome 17 (frontotemporal
      dementia with Parkinsonism (FTDP-17), and other tauopathies pathologically
      resembling PD plus AD, are often related to mutations of the tau gene, whereas
      familial PD with alpha-synuclein and Parkin mutations usually show no cognitive
      impairment. Mood disorders, in particular depression, and psychotic complications
      in both PD and DLB are related to complex involvement of noradrenergic and
      serotonergic systems, not confirmed in AD with depression, and both the
      prefrontal and limbic dopaminergic systems. The specific contributions of
      cortical and subcortical pathologies to mental dysfunction in PD and related
      disorders, their relationship to AD, and their genetic and aetiological
      backgrounds await further elucidation.

PMID- 10961432
TI  - Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach.
AB  - Neurofibrillary degeneration is a key histopathological brain lesion of Alzheimer
      disease (AD) and related neurodegenerative disorders such as frontotemporal
      dementia and Parkinsonism linked to chromosome 17 (FTDP-17), commonly referred to
      as tauopathies. Microtubule associated protein (MAP) tau, which is a major MAP of
      a normal mature neuron is abnormally hyperphosphorylated in tauopathies and is
      the major protein subunit of paired helical filaments (PHF)/straight filaments
      (SF) which accumulate in the soma (as neurofibrillary tangles) and dystrophic
      neurites (as neuropil threads and as dystrophic neurites surrounding the beta
      amyloid core in neuritic plaques in AD) of the affected neurons. Unlike normal
      tau which stimulates assembly and stabilizes microtubules, the abnormally
      hyperphosphorylated tau inhibits assembly and disrupts microtubules. The
      abnormally hyperphosphorylated tau competes with tubulin/microtubules in
      associating with normal tau, MAP1 and MAP2. This sequestration of normal MAPs by
      the abnormal tau results in the breakdown of the microtubules. The association of
      the abnormal tau with normal tau and not with MAP1 or MAP2 results in the
      formation of tangles of tau filaments. All these toxic properties of the
      abnormally hyperphosphorylated tau are eliminated by its enzymatic
      dephosphorylation. Activities of phosphoseryl/phosphothreonyl protein
      phosphatases (PP)-2A and PP-1 which can dephosphorylate the abnormal tau to a
      normal-like state are compromised in AD brain. Dephosphorylation by PP-2A and PP
      2B and to a lesser extent by PP-1 restores the normal microtubule assembly
      promoting activity in AD P-tau in vitro. Neurofibrillary tangles of PHF isolated
      from AD brain are also dissociated on in vitro dephosphorylation with PP-2A, and
      the tau released by this treatment can stimulate microtubule assembly. Thus, it
      appears that the abnormal hyperphosphorylation of tau leads to neurodegeneration
      through breakdown of the microtubule network and that the abnormal tau on
      association with normal tau forms neurofibrillary tangles of tau filaments i.e.
      PHF/SF. Increase in tau phosphatase activity is a promising approach to inhibit
      neurofibrillary degeneration and thereby the diseases characterized by this
      lesion.

PMID- 10961433
TI  - Understanding the role of estrogen on cognition and dementia.
AB  - There is growing evidence that post menopausal use of estrogen may have a
      beneficial effect on cognition and may reduce the risk of dementia. In a vast
      majority of studies, the use of estrogen replacement in the postmenopausal period
      was associated with a reduced risk of dementia. Meta-analyses of both
      retrospective case controlled and prospective studies indicate a 30% reduction in
      the risk of dementia, with larger effect sizes (50% reduction) reported in the
      latter. Some, but not all, large epidemiological studies indicate that estrogen
      use is associated with better performance on both verbal and visual memory
      testing in later life. However, studies of the effect of estrogen on patients
      with Alzheimer's disease are less convincing with minimal effects reported in
      open trials and following brief exposure. Biological mechanisms, which could be
      responsible for some of these effects, include activation of the cholinergic
      system, anti-oxidant action, neurotrophic stimulation and anti-amyloidogenic
      properties. Beneficial effects of estrogen in primary prevention but not
      secondary prevention of heart disease indicates that the ability to observe
      beneficial effects may depend on the point at which intervention occurs. Ongoing
      double-blind randomized clinical trial to determine if estrogen is a safe and
      effective treatment for the prevention of memory loss and Alzheimer's disease
      will be described. Future work will undoubtedly include the identification of
      specific estrogenic receptors in the central nervous system that can be
      selectively activated without adverse involvement of other biologic systems.

PMID- 10961434
TI  - Present and future of Alzheimer therapy.
AB  - Three major lines of drugs have been developed or are under development for the
      treatment of Alzheimer Disease (AD): cholinergic drugs (mainly cholinesterase
      inhibitors), anti-beta-amyloid drugs, estrogens and anti-inflammatories.
      Cholinesterase inhibitors are the only drugs presently approved in USA and Europe
      for the indication of AD. Cholinesterase inhibitors tested in clinical trials in
      Europe, USA and Japan include less than ten drugs, however most of these
      compounds have advanced to clinical trials III. Based on results related to a
      population of over 8,000 patients we conclude that several of these compounds
      have shown significant clinical efficacy and safety in the treatment of Alzheimer
      disease. There are, however, differences with regard to side effects. The major
      clinical effect is stabilization of cognitive function during a six- to 12-months
      period with a parallel improvement of behavioral symptoms. Long-term effect of
      cholinesterase inhibitors extending to a two year-period has been reported.
      Future applications of these drugs are treatment of other types dementias such as
      Lewy body dementia, vascular dementia and Down Syndrome dementia. Combination of
      cholinesterase inhibitors with estrogens, anti-oxidants and anti-inflammatories
      may represent a further improvement of the therapy. From the economical point of
      view, treatment with cholinesterase inhibitors is not cost neutral.

PMID- 10961435
TI  - Trials to slow progression and prevent disease onset.
AB  - Current treatments for Alzheimer's disease (AD) are largely symptomatic and
      improve cognition. Only a single trial of selegiline and vitamin E has been
      demonstrated to delay progression of the time to clinically important endpoints
      in this disease. Effective treatments currently under development are designed to
      either slow the rate of progression or delay the time of onset. Classes of agents
      currently being investigated include: antioxidants, anti-inflammatory agents,
      growth factors, hormones, and drugs designed to prevent the deposition or enhance
      the removal of amyloid. In addition to trials designed to slow the rate of
      progression, several primary prevention trials have already been initiated.
      Finally, a series of trials designed to prevent the development of AD in patients
      with mild cognitive impairment have been initiated.

PMID- 10961436
TI  - Epidemiologic clues to the causes and routes to prevention of Alzheimer disease.
AB  - Identification of epidemiologic risk factors serves many purposes. These include
      1) identification of high risk groups as potential targets for interventions; 2)
      identification of the candidate interventions (when the risk factor is
      susceptible to modification); and 3) suggestion of previously unsuspected causal
      mechanisms (when the risk relationship is unexpected and not readily explained by
      current causal theories). Two possible risk relationships will be discussed--one
      now well known and the other novel--that may provide a means of reducing the risk
      of Alzheimer's disease (AD). I will also suggest a causal theory that encompasses
      these epidemiologic observations and other recent data.

PMID- 10961437
TI  - Post-transcription modulation of the blood-brain barrier GLUT1 glucose
      transporter by brain-derived factors.
AB  - Brain-derived peptides or factors in the brain-derived preparation Cerebrolysin
      (Cl, EBEWE, Austria) increase the expression of the blood-brain barrier (BBB)
      GLUT1 glucose transporter via mRNA stabilization. The post-transcriptional
      regulation of the BBB-GLUT1 gene is principally exerted by interaction of cis
      regulatory elements located in the 3'-untranslated region of GLUT1 mRNA with
      cellular trans-acting factors (TAF). UV-cross linking and RNase T1 protection
      studies demonstrated the presence of 2 major GLUT1 RNA-TAF complexes named p88
      (stabilizing) and the p44 (destabilizing). The p88 TAF was detected in cytosol of
      brain endothelial cultured cells (ECL) as a duplex of molecular weight of
      approximately 88 kDa, which were defined A and B (high and low MW, respectively).
      Cl markedly increased the abundance of the BBB-GLUT1 p88 TAF (complex B) in ECL
      cells, without changes in the levels of the p88 complex A. This was also
      confirmed by antisense oligomer displacement of the GLUT1 RNA-TAF complex
      formation. Cl per se, did not bind to the GLUT1 mRNA, nor induced the expression
      of the destabilizing p44 TAF. Data presented here suggest that the increased
      stabilization of the GLUT1 transcript induced by Cl is associated with augmented
      levels of the GLUT1 stabilizing p88 TAF.

PMID- 10961438
TI  - A brain derived peptide preparation reduces the translation dependent loss of a
      cytoskeletal protein in primary cultured chicken neurons.
AB  - Neuronal cytoskeletal proteins like the microtubule associated protein 2 (MAP2)
      are objected to pathological proteolysis in case of Alzheimer's disease and brain
      ischemia. The neurotrophic peptidergic drug Cerebrolysin (EBEWE Arzneimittel,
      Austria, Europe) is produced by a standardized enzymatic break-down of lipid free
      porcine brain proteins. Cerebolysin protected MAP2 in primary neuronal cultures
      after a brief histotoxic hypoxia and in a rat model of acute brain ischemia.
      Furthermore the drug was shown to inhibit the proteases mu- and m-calpain dose
      dependently in several cell free protease activity assays. The question if the
      higher MAP2 levels are due to an alleviation of proteolysis, to a higher
      synthesis rate or both is addressed in the current investigation: Monitoring the
      MAP2 content of primary neuronal cell cultures over a period of eight days
      revealed MAP2 to reach a peak level on day six in vitro followed by a degradation
      phase. In other experiments the protein synthesis of Cerebrolysin treated and
      untreated cells was blocked with cycloheximide at that moment when all cells
      exhibited the same MAP2 content. After the following MAP2 degradation phase--i.e.
      after eight days in vitro--the MAP2 contents were determined by western blotting.
      Cerebrolysin treated cells contained more MAP2 than untreated controls proving
      that the drug protects MAP2 independently from de novo synthesis, although
      further work is in progress to investigate if the drug supplementary boosts this
      effect by increasing MAP2 synthesis.

PMID- 10961439
TI  - Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity.
AB  - Excitotoxicity might play an important role in neurodegenerative disorders such
      as Alzheimer's disease. In the mouse brain, kainic acid (KA) lesioning results in
      neurodegeneration patterns similar to those found in human disease. For this
      study, two sets of experiments were performed in order to determine if
      Cerebrolysin ameliorates the alterations associated with KA administration. In
      the first set of experiments, mice received intraperitoneal KA injections
      followed by Cerebrolysin administration, while in the second, mice were
      pretreated with Cerebrolysin for 4 weeks and then challenged with KA. Behavioral
      testing in the water maze and assessment of neuronal structure by laser scanning
      confocal microscopy showed a significant protection against KA lesions in mice
      pretreated with Cerebrolysin. In contrast, mice that received Cerebrolysin after
      KA injections did not show significant improvement. This study supports the
      contention that Cerebrolysin might have a neuroprotective effect in vivo against
      excitotoxicity.

PMID- 10961440
TI  - Cerebrolysin reduces microglial activation in vivo and in vitro: a potential
      mechanism of neuroprotection.
AB  - Neurotrophins, such as NGF, BDNF and NT-3 play a regulatory role on the function
      of microglial cells in vivo and in vitro, and the identification of new compounds
      with neurotrophic properties is becoming a new strategy for the prevention and/or
      treatment of neurodegenerative disorders. In this study we describe the use of
      two different models to demonstrate the ability of Cerebrolysin to reduce
      microglial activation. The results of these in vitro and in vivo studies indicate
      that Cerebrolysin might exert a neuroimmunotrophic activity reducing the extent
      of inflammation and accelerated neuronal death under pathological conditions such
      as those observed in neurodegenerative diseases.

PMID- 10961441
TI  - Clinical experience with Cerebrolysin.
AB  - Cerebrolysin is a peptidergic drug which displays neurotrophic action in various
      animal models. It is used for the treatment of dementia and in this report we
      provide evidence for the long-term clinical efficacy of Cerebrolysin in
      Alzheimer's disease. This evidence is based on our clinical experience with
      Cerebrolysin, stemming from our participation in a double-blind, placebo
      controlled clinical trial, a compassionate use programme initiated thereafter,
      and a PET study. Our data suggests, that Cerebrolysin is a safe and effective
      treatment for Alzheimer's disease and that repeat treatments may maintain
      function in patients over the long-term.

PMID- 10961442
TI  - Approach towards an integrative drug treatment of Alzheimer's disease.
AB  - At present pharmacotherapy of Alzheimer's disease (AD) is limited to
      acetylcholinesterase inhibitors. These drugs produce small, but consistent
      improvements of memory and global function, some are also positively influencing
      activities of daily living. This therapeutic approach neglects the complexity of
      AD and the fact that most of the degenerating neurons are not cholinergic.
      Acetylcholinesterase inhibitors are symptomatic drugs, with no influence on
      disease progression. There is a need for disease modifying compounds, or
      preventive drugs. Data are indicating that vitamin E has some ability to
      influence the disease progression. The potency of non-steroidal anti-inflammatory
      drugs (NSAIDs) or estrogen as preventive agents has to be explored further in
      prospective clinical studies. The initial hope in the use of naturally occurring
      neurotrophic factors, like nerve growth factor, to rescue cholinergic neurons
      from degeneration and to restore cognitive function has been disappointed in
      first, small clinical studies. The peptidergic drug Cerebrolysin exhibiting
      neurotrophic stimulation, neuroimmunotrophic regulation and induction of BBB
      glucose transporter expression, might be able to address the pathological changes
      of AD at different levels simultaneously. In addition to an impressive
      preclinical database, results from 3 placebo-controlled, double-blind studies
      demonstrate significant improvements of cognitive performance, global function
      and activities of daily living in AD patients. In all studies persisting
      improvements, up to 6 months after drug withdrawal, indicate a powerful disease
      modifying activity.

PMID- 10961443
TI  - Oral Cerebrolysin enhances brain alpha activity and improves cognitive
      performance in elderly control subjects.
AB  - Cerebrolysin is a porcine brain derived peptide preparation with potential
      neurotrophic activity. The effects of a single oral dose of the Cerebrolysin
      solution (30 ml) on brain bioelectrical activity and on cognitive performance
      were investigated in healthy elderly people. A single oral dose of Cerebrolysin
      induced a progressive increase in relative alpha activity power from 1 to 6 hours
      after treatment in almost all the brain electrodes in elderly control subjects.
      As compared with baseline alpha power (45.8+/-9.5%), the increase in relative
      alpha activity in the left occipital electrode (O1) reached significant values at
      1 hour (57.2+/-8.5%; p < 0.05), 3 hours (59.4+/-7.6%; p < 0.05) and 6 hours
      (63.4+/-9.8%; p < 0.05) after Cerebrolysin administration. Enhancement in
      relative alpha power was accompanied by a generalized decrease in slow delta
      activity that was maximum at 6 hours after Cerebrolysin intake. A significant
      improvement in memory performance, evaluated with items of the ADAS cog, was also
      found in elderly people taken a single dose of oral Cerebrolysin (6.9+/-1.0
      errors at baseline versus 4.9+/-1.0 errors after treatment; p < 0.01). This
      memory improvement was more evident in recognition (2.8+/-0.6 errors vs. 1.5+/
      0.7 errors; p < 0.05) than in recall tasks (4.1+/-0.5 errors versus 3.4+/-0.5
      errors; ns). These data indicate that Cerebrolysin potentiates brain alpha
      activity, reduces slow EEG delta frequencies and improves memory performance in
      healthy elderly humans, suggesting that this compound activates cerebral
      mechanisms related to attention and memory processes. According to the present
      results, it seems that oral Cerebrolysin might be useful for the treatment of
      memory impairment and brain damage in eldely subjects with or without
      neurodegenerative disorders.

PMID- 10961445
TI  - Selective targeting of avidin/mannose 6-phosphate receptor chimeras to early or
      late endosomes.
AB  - In this study we have used the Semliki forest virus expression system to
      transiently express chimeric proteins that contain transmembrane and cytoplasmic
      domains of the cation-independent mannose 6-phosphate receptor (CI-MPR) fused to
      chicken avidin. Immunofluorescence and electron microscopy studies showed that
      the chimeric protein with the entire cytoplasmic domain of CI-MPR was transported
      to late endosomes, where it accumulated. We made use of the biotin-binding
      capacity of lumenal avidin, and found that, in agreement with this distribution,
      the chimeric protein could be labelled with biotinylated HRP endocytosed for a
      long, but not a brief, period of time. However, truncation of the C-terminal tail
      distal to the rapid endocytosis motif (YKYSKV), caused the truncated chimera to
      be transported to, and accumulated within, early endosomes. This truncated
      chimera did not reach recycling early endosomes labelled with internalised
      transferrin, to any significant extent, but was accessible to biotinylated HRP
      internalised for 5 min (or for longer periods at 19 degrees C). Coinfection of
      these chimeras showed that they follow the same route from the TGN to the early
      endosomes. We conclude that the sequence distal to the endocytosis motif contains
      the signals which are required for efficient transport to late endosomes. Our
      results also suggest that the YKYSKV sequence close to the CI-MPR transmembrane
      segment is sufficient for targeting to sorting early endosomes.

PMID- 10961444
TI  - Apical macropinocytosis in polarized MDCK cells: regulation by N-ethylmaleimide
      sensitive proteins.
AB  - In cells tested so far endocytosis seems to be dependent on N-ethylmaleimide
      (NEM)-sensitive proteins, and treatment with NEM results in a complete block of
      endocytosis. We here demonstrate that treatment of polarized MDCK I cells with
      NEM strongly increased endocytosis of ricin and horseradish peroxidase at the
      apical side, and electron microscopy revealed NEM-induced formation of large
      macropinosomes at the apical pole. The NEM-stimulated apical endocytosis seemed
      to involve phosphatidylinositol-3 kinase, protein kinase C and phospholipase D
      and it was dependent on ATP. Moreover, in contrast to endocytosis in nonpolarized
      cells ricin endocytosis at the basolateral side continued in the presence of NEM
      whereas endocytosis of transferrin was blocked. Furthermore, recycling of ricin
      endocytosed in the absence of NEM was not inhibited on either side upon addition
      of NEM demonstrating the existence of a NEM-resistant fusion machinery. The
      results suggest that the fusogenic property of both the apical and the
      basolateral plasma membrane of MDCK cells differs from that typically observed in
      cells unable to polarize.

PMID- 10961446
TI  - The Cdc42p GTPase is targeted to the site of cell division in the fission yeast
      Schizosaccharomyces pombe.
AB  - The Rho-family GTPase Cdc42p regulates many aspects of cell polarity and growth
      in eukaryotic cells, including the organization of the actin cytoskeleton. To
      further examine Cdc42p function in the fission yeast Schizosaccharomyces pombe, a
      functional green fluorescent protein (GFP)-Cdc42p fusion protein was generated.
      GFP-Cdc42p was observed at the medial region of the cell at the cell-division
      site early in cytokinesis and remained there through cell separation, and was
      also localized to the periphery of the cell and to internal membranes.
      Unexpectedly, treatment with the actin-depolymerizing drug latrunculin-A
      disrupted the medial region targeting pattern, and cells deficient in the actin
      binding proteins tropomyosin and profilin also did not exhibit medial GFP-Cdc42p
      staining. In addition, medial GFP-Cdc42p localization was eliminated in a number
      of cytokinesis mutants, including strains defective in assembling the medial
      actinomyosin ring, medial ring contraction, and septum assembly. GFP-Cdc42p
      targeting was less affected in mutants that formed misplaced or multiple septa.
      These results suggest that the localization of Cdc42p at the cell-division site
      was dependent upon the actin cytoskeleton and that Cdc42p may function in the
      interdependent processes of cytokinesis and septation.

PMID- 10961447
TI  - The epidermal intermediate filament proteins of tunicates are distant keratins; a
      polymerisation-competent hetero coiled coil of the Styela D protein and Xenopus
      keratin 8.
AB  - Two novel cytoplasmic intermediate filament (IF) proteins (C and D) from the
      tunicate (urochordate) Styela are characterised as putative keratin orthologs.
      The coexpression of C and D in all epidermal cells and the obligatory
      heteropolymeric IF assembly of the recombinant proteins argue for keratin
      orthologs, but the sequences do not directly reveal which protein behaves as a
      keratin I or II ortholog. This problem is solved by the finding that keratin 8, a
      type II keratin from man or Xenopus, forms chimeric IF when mixed with Styela D.
      Mutant proteins of Styela D and keratin 8 with a single cysteine in equivalent
      positions show that these chimeric IF are, like vertebrate keratin filaments,
      based on the hetero coiled coil. We propose that Styela D retains, in spite of
      its strong sequence drift, important molecular features of type I keratins. By
      inference Styela C reflects a type II ortholog. We discuss that type I to III IF
      proteins are expressed along the chordate branch of metazoa.

PMID- 10961448
TI  - A CpG-rich RNA and an RNA helicase tightly associated with the DNA demethylation
      complex are present mainly in dividing chick embryo cells.
AB  - In the developing chicken embryo, active DNA demethylation requires both RNA and
      proteins (Nucleic Acids Res. 25, 2375-2380, 1997; ibid. 25, 4545-4550, 1997, FEBS
      Lett. 449, 251-254, 1999a). In vitro assays indicate that in the 5- and 12-day
      old embryos the highest specific activity of 5-methylcytosine DNA glycosylase is
      found in the brain, the eyes and the skin. In situ hybridization with antisense
      CpG-rich RNA tightly associated to the DNA demethylation complex shows a
      restricted expression pattern only in proliferating tissues such as the
      neuroepithelia of the brain in 5-day-old embryos. The RNA is absent in
      differentiated tissues like the skeletal and heart muscle, liver and the
      crystallin-producing cells in the lens. The CpG-rich RNA is transcribed in a
      developmental stage-specific rather than in a cell-specific manner. In contrast
      transcripts of DNA methyltransferase are found in dividing and quiescent cells.
      In situ hybridization with a probe of a RNA helicase which is also associated
      with the DNA demethylation complex shows a very similar localization in
      mitotically active tissues as the CpG-rich RNA. The content of 5-methylcytosine
      in individual cells was determined with a specific monoclonal antibody and
      cytometric analysis on tissue sections. The results indicate that proliferating
      cells have on the average 15% more methylated cytosines than non-dividing cells.
      This represents roughly 3x10(6) more methylation sites per haploid genome.

PMID- 10961449
TI  - Inflated wings, tissue autolysis and early death in tissue inhibitor of
      metalloproteinases mutants of Drosophila.
AB  - In vertebrates, tissue inhibitors of metalloproteinases (TIMPs) play key roles in
      extracellular matrix (ECM) homeostasis and growth control. Deletion of the
      recently cloned Timp gene of Drosophila results in a subviable phenotype. Adult
      flies display inflated wings similar to integrin mutants, suffer from a bloated
      gut and progressive dissolution of internal tissues, and die prematurely. Our
      results demonstrate that the Timp gene product controls selective aspects of ECM
      function in Drosophila, and suggest that it is involved in cell adhesion/cell
      signaling pathways. Hence, Drosophila Timp mutants may prove useful as a model
      system for a wide variety of pathological conditions related to ECM
      dysregulation.

PMID- 10961450
TI  - Alpha v integrin antagonists induce the disassembly of focal contacts in melanoma
      cells.
AB  - In recent years, several antagonists of alpha(v)beta3 have been used to develop
      therapeutic approaches to the treatment of melanoma neoplasia. We studied the
      effects of anti-alpha(v)-integrin-blocking antibodies on attached M21 melanoma
      cells, the cellular distribution of alpha(v)-integrin and the molecular
      organization of focal structures. Anti-alpha(v)-integrin-blocking antibodies 17E6
      and LM609, and an anti-alpha(v)beta3-integrin antagonist peptide cRGD 85189
      induced detachment of M21 melanoma cells cultured for 24 hours on various
      substrates. cRGD was the most effective antagonist, reducing the number of
      adherent cells by 80%, while 17E6 reduced adhesion by only 30%. Light- and
      electron microscopy revealed attached cells with a flat shape and well-formed
      actin cytoskeleton. After treatment, cells became rounded and detached from the
      culture dish. alpha(v)-Integrins and focal-contact proteins were observed at
      adhesion sites in focal structures by immunocytochemistry. After treatment,
      however, cell rounding was accompanied by disorganization of the actin filaments
      and redistribution of alpha(v)-integrins and most of the focal proteins studied,
      except vinculin and tensin. Our results indicate that treatment of M21 melanoma
      cells with a(v)-integrin antagonists disrupts the actin cytoskeleton,
      redistributes a(v)-integrin and induces molecular disassembly of focal contacts.

PMID- 10961451
TI  - In vitro production of superoxide and nitric oxide (as nitrite and nitrate) by
      Mytilus galloprovincialis haemocytes upon incubation with PMA or laminarin or
      during yeast phagocytosis.
AB  - The phagocytic process is one of the most important elements of the self-defence
      system in mammals as well as in molluscs. In mammalian phagocytes, superoxide
      participates in the innate defence system by combining with nitric oxide to
      generate peroxynitrite, a strong oxidant that possesses highly cytotoxic
      properties against bacteria. To evidence a role of nitric oxide in the self
      defence system of the marine bivalve Mytilus galloprovincialis similar to the
      role observed in the mammalian defence system, we measured the generation of
      superoxide and nitrite/nitrate (the stable end products of nitric oxide) upon in
      vitro stimulation of M. galloprovincialis haemocytes with PMA, laminarin, LPS and
      by phagocytosis of Saccharomyces cerevisiae (yeast cells). We show that
      stimulation with PMA, laminarin and yeast cell phagocytosis promotes superoxide
      and nitrite/nitrate generation from M. galloprovincialis haemocytes. Inhibitors
      of NADPH oxidase and inhibitors of NO synthase decreased the nitrite/nitrate
      levels generated by M. galloprovincialis haemocytes showing that both NADPH
      oxidase and NO synthase pathways are involved in the self-defence system of M.
      galloprovincialis.

PMID- 10961452
TI  - Molecular biology of Streptococcus pneumoniae: an everlasting challenge.
AB  - Streptococcus pneumoniae is a model for elucidating: 1) recombination steps of
      DNA, from its discovery to polarity of integration; 2) long-patch mismatch
      repair, short-patch repair triggered by A/G and exclusion of deletions; 3)
      resistance to beta-lactam antibiotics; and 4) factors of virulence. Several of
      these topics remain a challenge for future investigations.

PMID- 10961453
TI  - Virulence factors and the pathogenesis of disease caused by Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae is a major pathogen of man causing diseases such as
      pneumonia, meningitis and otitis media. The mechanisms by which this organism
      causes these diseases are still largely unknown. The use of molecular approaches
      to identifying and studying putative virulence factors in combination with the
      application of animal models has allowed some of the mechanisms of the disease
      process to be defined.

PMID- 10961454
TI  - Phosphocholine of pneumococcal teichoic acids: role in bacterial physiology and
      pneumococcal infection.
AB  - Pneumococci have an absolute nutritional requirement for choline. Choline is
      incorporated as phosphocholine (PCho) into lipoteichoic (LTA) and teichoic acid
      (TA). The PCho residues are required for transformability, the activity of
      autolysins, the separation of daughter cells after cell division and for
      anchoring a family of surface proteins which play important roles in pneumococcal
      infection. The genes encoding the enzymes for PCho incorporation are described.
      Two strains that acquired the ability to grow in the absence of choline are
      discussed.

PMID- 10961455
TI  - Current trends in capsular polysaccharide biosynthesis of Streptococcus
      pneumoniae.
AB  - The capsular gene cluster (cap/cps) of 13 out of the 90 known pneumococcal types
      has been sequenced. The cap/cps operon, located between dexB and aliA in the
      Streptococcus pneumoniae chromosome, contains some of the genes responsible for
      the synthesis of the type-specific polysaccharide flanked by four conserved open
      reading frames. The biochemical function of only a few capsular genes has been
      established, whereas the role of the flanking regions is controversial.
      Remarkably, only one gene (tts) located outside the cap locus is required for the
      synthesis of type 37 capsule. Moreover, other genes not linked to the cap gene
      cluster are also needed for capsule synthesis in pneumococcus.

PMID- 10961456
TI  - Biological roles of two new murein hydrolases of Streptococcus pneumoniae
      representing examples of module shuffling.
AB  - We have found two murein hydrolases (LytB and LytC) tightly bound to the cell
      envelope that have completely changed the domain building plan previously
      reported for the murein hydrolases of Streptococcus pneumoniae. The active center
      of LytB and LytC is located at the C-terminal, whereas the binding domain is at
      the N-terminal. LytC has been characterized as the first lysozyme of S.
      pneumoniae and behaves as an autolysin at 30 degrees C. LytB appears as the main
      hydrolase responsible for cell separation since inactivation of lytB leads to the
      formation of long chains of more than 100 cells. These findings indicate that
      genetic adaptation of mobile domains is extremely efficient in pneumococcus.

PMID- 10961457
TI  - Regulation of competence for genetic transformation in Streptococcus pneumoniae:
      a link between quorum sensing and DNA processing genes.
AB  - Competence for genetic transformation in pneumococcus depends on the coordinated
      functioning of a dispersed regulon responsible for production of proteins active
      in DNA binding, uptake, and recombination. This regulon is characterized by a
      shared noncanonical promoter consensus, TACGAATA, and is capable of 100-fold
      expression modulations. This review discusses recent evidence that its regulation
      depends on a novel sigma factor, itself controlled by an autostimulatory quorum
      sensing system that acts through an extracellular peptide signal.

PMID- 10961458
TI  - Transformation in Streptococcus pneumoniae: mosaic genes and the regulation of
      competence.
AB  - The presence of highly divergent mosaic blocks in penicillin binding protein
      genes responsible for penicillin resistance in Streptococcus pneumoniae implies
      that transformation is an important tool for the evolution of this pathogen.
      Genetic competence depends on production of the competence signaling peptide CSP,
      the processed product of comC, which is curiously part of a mosaic gene
      arrangement itself. Expression of comC is part of a complex regulatory network
      involving at least two receptor kinase/transcriptional regulator pairs: ComD/E,
      which is responsible for induction, and CiaH/R, which inhibits expression of the
      comCDE operon.

PMID- 10961459
TI  - Is the Ami-AliA/B oligopeptide permease of Streptococcus pneumoniae involved in
      sensing environmental conditions?
AB  - Streptococcus pneumoniae is a fastidious obligate parasite requiring several
      amino acids for growth. Oligopeptide uptake mediated by the Ami ABC permease is
      therefore important for nutrition but this could not account for the highly
      pleiotropic phenotype exhibited by Ami mutants. The hypothesis that peptide
      transport plays a pivotal role in sensing environmental conditions and indirectly
      modulates the expression of several genes is discussed.

PMID- 10961460
TI  - Estimating the relative contributions of mutation and recombination to clonal
      diversification: a comparison between Neisseria meningitidis and Streptococcus
      pneumoniae.
AB  - Both Neisseria meningitidis and Streptococcus pneumoniae are naturally
      transformable species and are known to be freely recombining in the wild. Large
      multilocus sequence typing (MLST) datasets have been generated for these species.
      Here we outline an approach which exploits these data sets in order to quantify
      the extent of recombination, thus enabling meaningful comparisons between the two
      species. Two parameters are estimated; the rate at which recombination changes
      alleles, compared to point mutation, and the rate at which recombination changes
      individual nucleotide sites, compared to point mutation. Estimates for the former
      parameter are 4:1 in the meningococcus (i.e. alleles are changed four-fold more
      frequently by recombination than by mutation), and 10:1 in the pneumococcus.
      However, estimates for the latter parameter are at least 80:1 in the
      meningococcus (i.e. an individual nucleotide site is at least 80-fold more likely
      to change by recombination than by mutation) and 50:1 in the pneumococcus. These
      data imply that recombination events, compared to mutational events, may be more
      common in the pneumococcus than in the meningococcus. However, because it is a
      more diverse species, each recombinational exchange in the meningococcus results
      in more nucleotide changes on average.

PMID- 10961461
TI  - Mechanisms and spread of fluoroquinolone resistance in Streptococcus pneumoniae.
AB  - The development of fluoroquinolones (FQs) with enhanced activity against
      Streptococcus pneumoniae is a potential advance in the treatment of pneumococcal
      infections, particularly those due to beta-lactam-resistant pneumococci. However,
      FQ-resistant clinical isolates selected by the older FQs have already been
      reported, with mutation(s) in both FQ targets conferring cross-resistance to
      newer FQs. It is likely that recombinational events between topoisomerase genes
      from related species of streptococci contribute to the spread of FQ resistance in
      S. pneumoniae. A scenario resembling that of the worldwide spread of resistance
      to beta lactams should be anticipated.

PMID- 10961462
TI  - Internalizing DNA.
AB  - The steps involved in the transformation of Bacillus subtilis are reviewed. These
      include the initial binding, processing and passage of DNA across the cell wall
      and transport across the plasma membrane. Our understanding of the roles of the
      proteins known to be required for these steps is reviewed.

PMID- 10961463
TI  - Bacillus subtilis homologous recombination: genes and products.
AB  - Homologous recombination plays a critical role in maintaining gene
      diversification and genome stability. Fourteen Bacillus subtilis recombination
      gene products have been genetically characterised and classified into five
      different epistatic groups. At least seven other recombination genes could be
      predicted. Recombination gene products which define activities that help RecA to
      process DNA repair and recombination have been studied, but those that processed
      recombination intermediates into products (post-synaptic stage) await
      elucidation.

PMID- 10961464
TI  - Genetic competence in Helicobacter pylori: mechanisms and biological
      implications.
AB  - Helicobacter pylori is naturally competent for genetic transformation. The comB
      locus, consisting of the open reading frames orf2, comB1, comB2, and comB3, is
      involved in natural transformation competence. Homologies of the ComB proteins
      with components of the type IV secretion apparatus (VirB9 and VirB10) from the Ti
      plasmid of Agrobacterium tumefaciens, as well as proteins involved in conjugation
      of plasmids RP1 and RP4, suggest a similar organization of DNA import
      (transformation) in H. pylori with well-known DNA export systems.

PMID- 10961465
TI  - Sex pheromones and gene transfer in Enterococcus faecalis.
AB  - Cell-density-dependent regulatory controls have been recognized in recent years
      to play major roles with regard to many microorganisms. In gram-negative bacteria
      very often N-acyl-homoserine lactones act as 'quorum-sensing' regulators, whilst
      gram-positive bacteria mainly use peptides to monitor their cell density. The so
      called sex pheromone system of Enterococcus faecalis is just one example of the
      latter type of regulation. The system is a complex one; in this communication, I
      will discuss in particular the potential role of the peptides to also act as
      virulence factors.

PMID- 10961466
TI  - Selectivity of oxymetazoline for urethral pressure vs blood pressure in the
      anaesthetized female rabbit.
AB  - OBJECTIVE: The aim of this study was to test alpha-adrenergic reference agonists
      for tissue selectivity in the urethra and to pharmacologically characterize the
      functional alpha-adrenoceptor type of the female rabbit urethra in vivo. MATERIAL
      AND METHODS: The effect of alpha-adrenergic agonists and antagonists on the
      urethral pressure was compared with that on blood pressure and heart rate
      measured simultaneously in the anaesthetized female rabbit. RESULTS:
      Oxymetazoline, NS-49, phenylephrine and phenylpropanolamine enhanced the urethral
      pressure in a dose-dependent manner. Phenylephrine and phenylpropanolamine also
      enhanced the blood pressure with significantly lower ED50 (dose that gives half
      of the maximal enhancing effect) values than for the urethral pressure. This was
      in contrast to oxymetazoline and NS-49. The ED50 values for oxymetazoline on
      urethral pressure, and systolic and diastolic blood pressure were 0.00067, 0.0030
      and 0.0020 mg/kg, respectively. The ED50 values for NS-49 on urethral pressure,
      and systolic and diastolic blood pressure were 0.019, 0.21 and 0.18 mg/kg,
      respectively. Clonidine and UK 14,304 had no effect on urethral or blood
      pressure. The oxymetazoline-evoked increase in urethral pressure was inhibited by
      WB-4101 with an ID50 (dose that gives half of the inhibitory effect)
      significantly lower than that for rauwolscine. CONCLUSIONS: The results suggest
      that in the female rabbit in vivo activation of alpha1-adrenoceptors increased
      the urethral pressure. Phenylephrine and phenylpropanolamine, in contrast to
      oxymetazoline and NS-49, selectively enhanced blood pressure as compared with
      urethral pressure. Provided that the present results also have validity in
      humans, it would seem possible to develop urethra-selective drugs for treatment
      of stress incontinence with few or no cardiovascular side-effects.

PMID- 10961467
TI  - Percutaneous nephropexy.
AB  - OBJECTIVE: The authors present a 12-year (1986-98) study of a new procedure
      called percutaneous nephropexy (PCNP). This procedure was performed on 51 renal
      ptosis patients at two urological departments (in Pakistan and Hungary) with
      satisfactory results. The idea for PCNP was adapted from the observation that
      after drain insertion following nephrostomy a scar is quite sufficient to hold
      the kidney in place. That idea was used to fix the kidney at the required level.
      MATERIAL AND METHODS: Thirteen patients complained of a palpable mobile mass in
      the abdomen while others suffered from pain in their affected flank with
      recurrent attacks of urinary tract infection. On ultrasonic examination the
      kidney was found to be lower than the normal position. This observation was
      confirmed by a standing intravenous urography (IVU) examination that also showed
      a tortuous ureter. Nine patients also had a stone in the affected kidney. The
      operation involved puncture and dilatation of a channel through the lower calyx.
      RESULTS: Control IVU examination was performed after wound healing and was
      repeated 2 months after the operation, followed by consecutive ultrasonic
      examinations. Standing X-ray films obtained after contrast material injection
      showed the kidney to be at a higher level with a straight ureter. Forty-five
      patients (88.2%) recovered completely. CONCLUSION: In the authors' opinion PCNP
      is a good alternative to open nephropexy operations in renal ptosis cases,
      particularly when laparoscopic surgery facilities are not available. Although
      PCNP was developed in circumstances in which the availability of equipment was
      restricted, in terms of benefits it is comparable with laparoscopic nephropexy.

PMID- 10961468
TI  - Urinary phytate in calcium oxalate stone formers and healthy people--dietary
      effects on phytate excretion.
AB  - The phytate urinary levels in a group of active calcium oxalate stone formers
      were studied and compared with those found in healthy people. Urinary phytate was
      significantly lower for stone formers. If deficit of the capacity to inhibit
      crystallization of calcium salts is considered an important factor related to
      calcium stone formation, the excretion of low phytate amounts could be an
      important risk factor in the development of this type of renal calculi. The
      influence of dietary phytate on urinary excretion was also studied. Clearly
      maintenance of a phytate-free diet significantly decreased the urinary excretion
      of phytate (about 50% after 36 h). This demonstrated the importance of dietary
      phytate in maintaining adequate urinary levels to permit effective
      crystallization inhibition of calcium salts and consequently preventing renal
      stone development.

PMID- 10961469
TI  - Are preoperative parameters of unilateral pyelo-ureteric junction obstruction in
      children predictive of postoperative function improvement?
AB  - OBJECTIVES: Surgery on the pyelo-ureteric junction obstruction (PUJO) has long
      been thought to affect postoperative renal function. However, preoperative
      assessment of which kidneys will benefit from such surgery remains unreliable.
      MATERIAL AND METHODS: Pre- and postoperative data relating to renal function were
      obtained by renal scan for 69 patients who were operated upon for PUJO. These
      patients were divided into two groups: group A (improved differential renal
      function) and group B (unimproved or decreased differential renal function). The
      two groups were then compared with regard to age at operation and presence or
      absence of clinical symptoms. Ultrasound (anteroposterior diameter of the pelvis,
      parenchymal thickness) and renal scan (glomerular filtration rate, differential
      renal function of the affected kidney, obstructive pattern) parameters were also
      taken into consideration. Some variables were also made dichotomous (pelvic
      diameter < or > 15 mm, parenchymal thickness < or > 5 mm, differential renal
      function < or > 40%). Statistical correlation was sought with parametric and non
      parametric tests. RESULTS: No correlation whatsoever was found between the two
      groups for any of the parameters under consideration, so that any attempt at
      logistical regression analysis failed. CONCLUSIONS: None of the currently adopted
      diagnostic tests can be used to indicate which renal units will benefit from
      surgery through an improved renal function. The presence or absence of clinical
      symptoms does not appear to affect renal function either. There is evidence that
      parents should be provided with such information when giving their informed
      consent to pyeloplasty.

PMID- 10961470
TI  - Usefulness of urodynamic examination in female urinary incontinence--lessons from
      a population-based, randomized, controlled study of conservative treatment.
AB  - OBJECTIVE: To test the usefulness of urodynamic examination in female urinary
      incontinence. MATERIAL AND METHODS: As part of a population-based, randomized,
      controlled treatment study in general practice, the control group was offered
      urodynamic examination before and after delayed treatment starting 6 months after
      inclusion in the study, i.e. after the first outcome evaluation comparing the
      initially treated group with the control group. The intervention group was
      offered urodynamic examination only after the final outcome evaluation at 12
      months. Eighty-seven women, aged 50-74, from three Norwegian municipalities
      participated. RESULTS: There was no difference in treatment outcome whether the
      patients had urodynamic examination or not. Eleven patients (26% of 42 control
      patients) had their diagnosis revised after urodynamic examination, ten of them
      with a subsequent change in treatment. The outcome for this group was no
      different than for the other patients. As a subgroup, the 11 patients had more
      severe leakage (p = 0.048) and more previous gynecological operations (p = 0.038)
      than the other control group patients. CONCLUSIONS: Our study supports the idea
      that in general practice, or in rather unselected patients, women with urinary
      incontinence may be classified and treated without urodynamic examination. If
      there is little or no improvement during the first few months referral should be
      considered, and this should be done sooner for patients with severe incontinence
      or prior gynecological operations than for other patients.

PMID- 10961471
TI  - Transrectal ultrasound anatomy of the prostate and seminal vesicles in healthy
      men.
AB  - OBJECTIVE: This study involved transrectal ultrasound (TRUS) examination of the
      prostate and seminal vesicles in healthy males, for use as a reference. MATERIAL
      AND METHODS: A total of 125 men (aged 20-69 years) with no history or symptoms of
      urogenital disease underwent TRUS. Prostate size (both total and central gland),
      focal lesions such as calcifications, hyper- and hypoechoic areas, cysts, and
      size and lobulation of the seminal vesicles were noted and related to age.
      RESULTS: The prostate measured 19.2 +/- 4 cm3 and calcifications were found in
      23.1% of men aged 20-29 years compared with 35.5 +/- 12.5 cm3 and 83% for men
      aged 60-69 years. Overall, hyperechoic areas were found in 59.2% of those
      examined, cysts in 16.8% and hypoechoic areas in about 11%, predominantly in the
      peripheral zone. Totally normal sonograms were seen in 29% of the men under the
      age of 40 and in 5% of the men aged 40 or older. CONCLUSIONS: TRUS examinations
      of healthy males are seldom without sonographic changes. This study provides the
      frequencies with which these changes occur in healthy males of various ages, all
      without urogenital symptoms, and may be used for future comparisons with
      different pathological conditions.

PMID- 10961472
TI  - Clinical implications of free-to-total immunoreactive prostate-specific antigen
      ratios.
AB  - OBJECTIVE: A study was performed to evaluate the free-to-total prostate-specific
      antigen (PSA) ratio for discriminating benign prostatic hyperplasia (BPH) or
      prostate cancer in the intermediate PSA range (2.0-10.0 microg/l) in patients
      referred for prostate evaluation. In addition, the relationship of free-to-total
      PSA ratio and tumor grade in prostatic cancer cases, implying a higher
      concentration of complex PSA in poorly differentiated cancer, was assessed for
      its predictive value of tumor aggressiveness at the time of diagnosis. PATIENTS
      AND METHODS: Seven hundred and sixteen patients referred to the out-patient
      clinics of two urological departments were included in this prospective study.
      Blood samples were taken for total immunoreactive and free PSA (IMMULITE)
      determinations prior to any manipulation. The patients were grouped according to
      their PSA levels: 2.0-4.0 microg/l, 4.0-10.0 microg/l, 10.0-20.0 microg/l and >
      or = 20.0 microg/l. All patients were categorized, after histological
      confirmation, as having BPH (n = 423) or prostate cancer (n = 293). In patients
      with cancer the tumor grade was also assessed. RESULTS: In patients with serum
      immunoreactive PSA levels in the 2.0-4.0 microg/l range, a free-to-total PSA
      ratio lower than 22% predicted the presence of prostate cancer with a sensitivity
      of 67% and a specificity of 63%. The positive- and negative-predictive values
      were 29% and 90% respectively. Receiver-operating characteristic curve analysis
      indicated a free-to-total PSA ratio of 22% to be the optimum discriminatory level
      in this low PSA range. For patients with a serum PSA level between 4.0 and 10.0
      microg/l, the threshold ratio of 18% gave a sensitivity of 70%, a specificity of
      70%, a positive-predictive value of 46% and a negative-predictive value of 87%.
      Men with a well differentiated grade of prostate cancer had higher free-to-total
      PSA ratios than those with less differentiated tumors (p = 0.01). CONCLUSIONS:
      Our data indicate that the free-to-total PSA ratio, in patients with prostatic
      disease and with PSA levels in the 2.0-10.0 microg/l range, gives a significant
      improvement in prediction of cancer over the total immunoreactive PSA value
      alone. Because of the correlation between a higher tumor grade and a lower free
      to-total PSA ratio, this ratio may be helpful in assessing the risk of a poorly
      differentiated cancer.

PMID- 10961473
TI  - Palliative radiation with a radiolabeled diphosphonate (rhenium-186 etidronate)
      in patients with hormone-refractory disseminated prostate carcinoma.
AB  - MATERIAL AND METHODS: The present study investigates the safety and efficacy of
      2590 MBq rhenium-186 (186Re) etidronate (i.e. twice the activity normally used)
      administered intravenously in 15 patients with disseminated prostatic carcinoma
      and bone pain. RESULTS: Pain relief was observed in 11 of 14 evaluable patients
      (79%), 4 of whom became completely free from pain. Five of the responding
      patients also noted an improvement in daily activity and two found it possible to
      reduce or discontinue morphine medication. Pain relief occurred within one week
      in four patients, and within two weeks in eight of the responding patients. The
      mean duration of pain relief after the first course of 186Re-etidronate was 6
      weeks (range 4-10). The toxicity was mild (< or = grade 2), transient, and
      restricted to hematological toxicity. CONCLUSIONS: 186Re-etidronate provided
      rapid pain-relief and had mild toxicity in most patients with disseminated
      hormone-refractory prostatic carcinoma, but doubling the activity did not
      markedly improve the efficacy.

PMID- 10961474
TI  - The effect of low-dose acetylsalicylic acid on bleeding after transurethral
      prostatectomy--a prospective, randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: An increase in the loss of blood after ingestion of acetylsalicylic
      acid (ASA) has been reported after several types of surgery, but randomized
      placebo-controlled studies have exclusively been performed after coronary artery
      bypass surgery. The reported effects of ASA on bleeding after transurethral
      prostatectomy (TURP) have been conflicting. We have studied the effect of low
      doses of ASA (150 mg) on bleeding after TURP in a prospective, randomized, double
      blind, placebo-controlled trial. PATIENTS AND METHODS: Patients were randomized
      to receive either 150 mg ASA (n = 26) or placebo (n = 27) 10 days before surgery.
      The weight of resected tissue, operation time and blood loss, transfusion
      requirements and complications were recorded. RESULTS: There was no significant
      difference in the median operative blood loss between the groups (p = 0.528), but
      postoperatively the blood loss in the ASA group (median 284; quartiles 196-660
      ml) was significantly higher than in the placebo group (median 144; quartiles 75
      379 ml), (p = 0.011). No significant difference was observed between the groups
      regarding the amount of resected tissue (p = 0.209) or the operating time (p =
      0.297). In both groups the operative blood loss was significantly related to the
      amount of resected tissue (p < 0.005) and the operating time (p < 0.005). No
      significant difference in transfusion requirements (p = 0.280), time to catheter
      removal (p = 0.455) and hospital stay (p = 0.820) were observed between the
      groups. CONCLUSION: Long-term low-dose ASA therapy is associated with a
      significant increase in the postoperative blood loss after TURP, and although no
      significant difference in transfusion requirements was observed more units of
      blood were used in the ASA group. We advise that ASA therapy should be withdrawn
      10 days before TURP.

PMID- 10961476
TI  - Two different desmopressin (DDAVP) regimens in enuretic monozygotic twins with
      allergic diathesis.
AB  - Primary monosymptomatic nocturnal enuresis is a common complaint in paediatrics.
      Treatment with desmopressin nasal spray is one of the most often used
      pharmacological approaches, but concerning therapy interruption, to date no
      guidelines have yet been established. The aim of this study was to report the use
      of desmopressin in two monozygotic twin sisters to establish if tolerability and
      efficacy of treatment can be affected by different modalities of therapy
      interruption.

PMID- 10961475
TI  - Night-time polyuria and urine hypo-osmolality in enuretics identified by
      nocturnal sequential urine sampling--do they represent a subset of relative ADH
      deficient subjects?
AB  - Early morning urine osmolality was tested in two urinary specimens, one taken
      immediately upon awakening and the other approximately 30 min thereafter, in 52
      enuretic and 15 non-enuretic children. In a follow-up study, using the same study
      population, urine osmolality and volume were measured sequentially at 3-h
      intervals at 19.00, 22.00, 01.00, 04.00 and 07.00 h. Thereafter, all enuretics
      were treated by intranasal DDAVP for a 6-month period. There were no differences
      in urinary osmolality between enuretic and non-enuretic children when comparing
      the two early morning specimens. Nor were there any differences between groups in
      urine osmolalities at 19.00, 01.00 and 07.00 h. In contrast, at 04.00 h, urine
      osmolality was significantly lower in 17 of 52 enuretics [designated as ADH
      negative (ADH-)] compared to the remaining enuretics [designated as ADH-positive
      (ADH+)] and non-enuretic children (610 +/- 251 vs 995 +/- 195 and 1089 +/- 195
      mosmol/kg H2O, respectively, p < 0.05). This decreased osmolality was paralleled
      by an increase in urine production during the time period 01.00-04.00 (83 +/- 24
      vs 52 +/- 18 and 45 +/- 22 ml, respectively, p < 0.05). At the end of the 6-month
      period of DDAVP treatment, the percentage response was similar between the ADH-
      and ADH+ enuretics (79% vs 75%). However, the time taken to achieve a response
      was quicker in the ADH- subjects. These data suggest the existence of a subgroup
      of enuretics whose underlying pathophysiology is the development of nocturnal
      polyuria probably due to a relative night-time ADH deficiency. Nocturnal
      sequential monitoring of urinary osmolality, as described above, allows
      identification of this subgroup.

PMID- 10961477
TI  - Impaired renal arterial blood flow velocity in nephroptosis.
AB  - The diagnosis nephroptosis, as well as surgical treatment of the condition, has
      been profoundly questioned in recent decades. Here, we report on a case of
      nephropexy in a young woman with nephroptosis with complete resolution of
      symptoms and with correction of preoperatively abnormal 99mTc-DMSA scan and renal
      arterial Doppler examination.

PMID- 10961478
TI  - Successful management of retroperitoneal malignant fibrous histiocytoma involving
      both kidneys.
AB  - We report a rare case of a retroperitoneal inflammatory variant of malignant
      fibrous histiocytoma (MFH) involving both kidneys. The best treatment for MFHs is
      surgery with radical excision of the tumor. In this case the need to save at
      least one kidney meant tumorectomy was incomplete. The patient underwent adjuvant
      chemotherapy and 4 years later survives in a fairly good condition.

PMID- 10961480
TI  - Bladder rupture due to accidental oxygen insufflation via an indwelling urethral
      catheter--a report of two cases.
AB  - Two cases of bladder rupture caused by accidental insufflation of oxygen through
      an indwelling urethral catheter are described. Both patients were ill with
      multiple diseases. Conservative treatment, including an open indwelling urethral
      catheter, and surveillance of abdominal status seem appropriate when managing
      this complication.

PMID- 10961479
TI  - An unusual renal tumour.
AB  - Primary renal lymphoma is a rare disease. The basis for diagnosis of this entity
      has been described and its existence is widely accepted. Localized deposition of
      amyloid is also a rare phenomenon. A case of primary lymphoma with localized
      amyloid deposition is reported here.

PMID- 10961481
TI  - Subcutaneous bleeding: first sign of prostate cancer.
AB  - We present here a case of subcutaneous bleeding being the first recognized sign
      of prostate cancer.

PMID- 10961482
TI  - An unusual cause of retrograde ejaculation and hypertension.
AB  - A 39-year-old man presented with a 1-year history of retrograde ejaculation and a
      10-year history of drug-resistant hypertension. Diagnostic abdominal ultrasound
      revealed an open bladder neck during the filling phase and a retroperitoneal
      tumor. After surgical excision histology revealed an extra-adrenal
      pheochromocytoma, which should be included in the differential diagnosis of
      patients presenting with retrograde ejaculation and hypertension.

PMID- 10961483
TI  - Rare complication of an arteriovenous fistula for dialysis: glaucoma.
AB  - We present a rare complication of an arteriovenous fistula for haemodialysis.
      Incompetence of the anti-reflux mechanism associated with elevated venous
      pressure in the subclavian vein provided conditions for intense blood reflux to
      the left jugular territory and development of ipsilateral glaucoma, successfully
      treated by ligation of the left jugular veins.

PMID- 10961484
TI  - Glycemic control and cardiovascular diseases in Type 2 diabetes mellitus. Beyond
      fasting glycemia and glycosylated hemoglobin.

PMID- 10961485
TI  - Changes of bioelectrical impedance after a body weight reduction program in
      highly obese subjects.
AB  - We used bioelectrical impedance analysis (BIA) as an exploratory tool to monitor
      the changes in body composition induced by a short-term (3-wk) weight reduction
      (energy-restricted diet, moderate aerobic exercise conditioning and psychological
      counselling) in 175 highly obese subjects (body mass index, BMI=41.7+/-5.8
      kg/m2). The decrease in weight and BMI after the weight reduction program was
      3.4% (geometric mean, p<0.0001) and 3.7+/-1.3 kg/m2 (mean+/-SD, p<0.0001),
      respectively. Bioelectrical impedance (Z) increased of about the same value at
      each of the measured frequencies (from 6+/-10% at 5 kHz to 5+/-9% at 100 kHz,
      mean+/-SD, p<0.0001). A statistically significant increase in Z5:Z100 was also
      seen (p<0.0001), but its clinical significance is questionable owing to its low
      absolute value (<1%). Taken together, these data suggest that no clinically
      relevant change in body water distribution occurred in our subjects as a result
      of the weight reduction program. However, the changes in Z did not satisfactorily
      predict the changes in anthropometric dimensions despite the evidence of a
      substantial association between Z and anthropometry both before and after the
      weight reduction program. Thus, accurate predictions of body composition changes
      in obese subjects may require more than two BIA measurements so as to have a
      better description of the weight-losing process.

PMID- 10961486
TI  - Advanced glycation end-products in diabetes mellitus, with particular reference
      to angiopathy.

PMID- 10961487
TI  - A detailed examination of the clinical terms and concepts required for
      communication by electronic messages in diabetes care.
AB  - The wider electronic exchange of clinical information between heterogeneous
      information systems in the delivery of diabetes care demands a common structure
      in the form of a message standard. A European Standard electronic diabetes
      message is being developed in conjunction with CEN TC251. This paper describes
      the methodologies that the 1998 DO IT Workshop has used to identify potential
      areas of difficulty in the design and implementation of the preliminary message
      model. To facilitate implementation and to avoid ambiguity in electronic
      messaging it is particularly important that there is standardisation of the
      definitions of the clinical terms specifically used in diabetes care across
      systems. Comprehensive lists of such terms to describe all areas of diabetes care
      do not exist and there is a lack of harmonisation of definitions in many areas.
      Thus, to better understand the user requirements of diabetes messaging several
      approaches were adopted. A review of the clinical terms and concepts contained in
      pre-existing datasets was undertaken with detailed study of a number of specific
      areas of diabetes care, analysing the conceptual structure of all the clinical
      terms that they comprised. Consideration of several worst case clinical scenarios
      for messages to communicate was also made to identify deficiencies in the message
      structure. This activity confirmed the importance of creating a Standard for a
      superset or thesaurus of diabetes specific terms, with appropriate definitions,
      to harmonise data communication in different IT systems to facilitate messaging.
      A substantial number of new terms were identified in the workshop and these will
      form an important first step to accomplishing a first draft superset once fully
      analysed. It was also apparent that certain specific areas within diabetes care,
      but most particularly in nursing, dietetics and podiatry, need urgent work to
      further develop the concepts and terms. This needs to be facilitated for an
      appropriate group of such professionals. To achieve such a Standard, continued co
      operation with CEN/ISSS was recognised to be very important.

PMID- 10961488
TI  - Messages for communication of electronic health care records in diabetic care.
AB  - This paper summarises the current status of work to develop a European Standard
      message for communication information from Electronic Health Care Records. This
      is part of the current work programme of the Technical Committee of the European
      Standardization Committee concerned with Health Informatics. This Standardization
      process is aimed at providing a general solution to the requirements for
      electronic communication between a diversity of clinical information systems.
      However, the two priority areas chosen for initial validation are Primary Care
      and Diabetes Care. The second of these areas is being addressed in close liaison
      with a messaging sub-group of the Diabetes Optimization through Information
      Technology study group of the European Association for the Study of Diabetes.
      Good early progress has been made and the timetable for completion of this work
      is short. The project team hopes to complete their work by the end of 1998 and
      formal adoption as a European Standard is scheduled for mid 1999. At this stage
      suppliers of clinical information systems will be able to implement Standard
      messages to support the communication of Electronic Health Care Record
      information. Once the Standard has been widely implemented, diabetologists,
      general practitioners, other specialists and health professionals from other
      disciplines should be able to exchange clinical information in a safe and useful
      manner.

PMID- 10961489
TI  - Coming to terms with datasets for diabetes care.
AB  - The development of datasets for the recording, transfer, monitoring and
      improvement of diabetes care has to take into account the perspectives of
      different stakeholders. Success of a dataset is dependent on shared ownership,
      professional support, clear objectives and development by consensus. Different
      types of concepts are discernible that share similar features, including the
      classes of disease, qualitative observations, quantitative observations,
      procedures and record specific concepts. The identification of these types
      assists the development of a dataset by clarifying the characteristics that need
      to be defined. The specification of the component data items ideally requires
      adherence to established terminology principles where each concept is uniquely
      labelled by an unambiguous term. These identified concepts should also be
      exclusive, stable over time, defined, reusable and relevant. Attention should
      also be given to the scope of each concept and consistency in handling additional
      detail. The dataset overall should adhere to principles of time representation
      and be manageable, implementable, regulated, extendible, piloted and ethical.
      Consideration of these principles should improve the likelihood that a dataset
      will be widely adopted, integrated and be further developed in existing patterns
      care.

PMID- 10961490
TI  - Guidelines for the treatment of adults with severe head trauma (part I). Initial
      assessment; evaluation and pre-hospital treatment; current criteria for hospital
      admission; systemic and cerebral monitoring.
AB  - If pragmatic recommendations for treatment of severely head-injured patients
      could really be applied, they would probably have a considerable impact in terms
      of reduction in mortality and disability. Since 1995 a Group of Italian
      Neurointensivists and Neurosurgeons belonging to the Italian Societies of
      Neurosurgery (SINch) and Anesthesiology & Intensive Care (SIAARTI) has produced
      this first part of recommendations that are completed by Medical treatment (Part
      II) and Surgical treatment criteria (Part III). These recommendations reflect a
      multidisciplinary consent but are based on scientific evidence, when available,
      and take origin mainly from expert opinions and the current clinical and
      organizational situation. For this aspect they differ from other American and
      European guidelines, which are strictly based on criteria of proven efficacy.
      These recommendations aim at providing a practical reference for all those
      dealing with severe head injuries from first-aid to intensive care units, setting
      out the minimal goals of management to be reached throughout the country. For
      these reasons they need continual critical review and updating. Main clinical
      aims are: 1) to prevent secondary cerebral damage by continuous and meticulous
      maintenance of systemic homeostasis 2) to standardize methods of neurological
      evaluation and CT scan classification and scheduling; 3) to give simple
      indications for systemic and cerebral monitoring 4) to pragmatically discuss the
      organizational scenarios and specify the minimal safe clinical approach when
      patients are treated in non-specialized settings. Briefly, smooth tracheal
      intubation and ventilation in all comatose patients, administration of rapidly
      metabolized sedative and analgesic drugs to permit frequent neurological
      evaluation, restoration of volemia and systolic blood pressure above 110 mm Hg,
      oxygen saturation >95% and normocapnia, are all recommended from the very early
      treatment and transport. Homogeneity of language, reliable and correctly tested
      Glasgow Coma Score and pupillary reflexes, and a simple CT scan classification
      are recommended to improve communications and clinical decisions in the
      multidisciplinary setting of management. In comatose patients, cerebral perfusion
      pressure, intracranial pressure and oxygen jugular saturation must be monitored
      according to specific criteria, which are described. Therapy with
      hyperventilation and mannitol should be used only in case of clinical
      deterioration and uncal herniation. This therapy could be useful to gain time to
      reach neurosurgery. The aim of these recommendations is to achieve safer
      management of severely brain injured patients, immediate diagnosis of clinical
      deterioration and successful identification and treatment of surgical lesions.
      The impact of these guidelines requires further verification.

PMID- 10961491
TI  - Guidelines for the treatment of adults with severe head trauma (part II).
      Criteria for medical treatment.
AB  - Since 1995 a Group of Italian Neurointensivists and Neurosurgeons belonging to
      the Italian Societies of Neurosurgery (SINch) and Anesthesia & Intensive Care
      (SIAARTI) has produced some recommendations for treatment of adults with severe
      head trauma. They have been published in 3 parts: Part I (Initial assessment,
      Evaluation and pre-hospital treatment, Criteria for hospital admission, Systemic
      and cerebral monitoring), Part II (Medical treatment) and Part III (Surgical
      treatment criteria). These recommendations reflect a multidisciplinary consent
      and are mostly based on expert opinion. The main aim is to provide a practical
      reference for all those dealing with severe head injuries from first-aid to
      intensive care units, setting out the minimal goals of management to be reached
      throughout the Country. These recommendations need a continuous critical review
      and updating. Medical treatment is aimed at preventing or minimizing secondary
      brain damage following acute brain injury, provided that surgical masses have
      been promptly identified and removed. In order to assure cerebral perfusion,
      systemic hemodynamics and respiratory exchanges should be normal. Volemia is
      crucial, and mean arterial pressure should remain above 90 mmHg. Good general
      intensive care, including gastroprotection, water-electrolyte balance, infection
      control, nutrition and physiotherapy, is assumed as the basis for brain-oriented
      therapy. Intracranial hypertension requires an approach based on various steps.
      First, factors that can directly rise intracranial pressure (ICP) such as venous
      outflow obstruction, fever, pain etc. should be checked and corrected. Second,
      Mannitol, CSF withdrawal, sedation and moderate hyperventilation should be
      applied. This can be done by targeting specific problems with specific treatment
      (which is possible when the cause of ICP rise is known) or in a step-wise
      approach, by using less aggressive interventions before than more aggressive
      ones, with a higher risk of complications. Third, extreme treatment, such as
      barbiturates, should be reserved to cases with refractory intracranial
      hypertension. The main goal of ICP treatment is not simply ICP reduction, but the
      maintenance of adequate cerebral perfusion pressure.

PMID- 10961492
TI  - Guidelines for the treatment of adults with severe head trauma (part III).
      Criteria for surgical treatment.
AB  - The Guidelines of the surgical management of severe head injury in adults, as
      evolved by the Neurotraumatology Group of the Italian Neurosurgery Society and
      the Italian Society for Anaesthesia, Analgesia, Reanimation and Intensive Care
      are presented and briefly discussed. Guidelines presented here are of a pragmatic
      nature, based on consensus and expert opinion. Aspects pertaining to specific
      indications to surgery and/or to the possibility of conservative management of
      different traumatic intracranial lesions are highlighted. The importance of
      surgery in preventing secondary insults to the traumatised brain is emphasised.

PMID- 10961494
TI  - Solitary metastases to the cranial vault. Report of ten cases.
AB  - BACKGROUND: Metastatic spread of tumors to the skull is quite unusual and often
      represents a relevant diagnostic and therapeutic problem. Skull involvement can
      be observed in various neoplasms of epithelial origin (rarely in other tumors)
      and most often responsible are lung, breast, thyroid, kidney and prostate
      cancers. Less frequent than multiple involvement, single cranial vault lesions
      are often amenable to surgical resection instead of radiotherapy alone; scope of
      this paper is to highlight the key points of the management of such entities,
      including a brief review of the pathological and radiological features of these
      entities. METHODS: A retrospective study has enabled us to select from our files
      ten cases of surgically treated solitary cranial vault metastases, with a
      variable follow-up ranging from 6 months to 4 years. In all the cases the
      operation consisted in a monobloc resection and a cranioplasty for the repair of
      the defect. RESULTS: We have observed no perioperative morbidity or mortality; in
      all the cases surgery allowed histologic confirmation and immediate relief of
      neurological symptoms and cosmetic impairment (when present). CONCLUSIONS:
      Monobloc resection of solitary cranial vault metastatic lesions is an easy made
      and safe procedure, to be performed in every patient except the ones in poor
      general conditions, which are better addressed to radiotherapy alone.

PMID- 10961493
TI  - Acoustic intrameatal meningiomas.
AB  - BACKGROUND: The sporadic finding of an acoustic intrameatal meningioma stimulated
      the authors to the present study. An analysis of the cases previously reported in
      the literature aimed to outline a preliminary account about biological,
      radiological and surgical specific hallmarks of these tumours. METHODS: Eight
      previous cases of meningiomas, meeting the prerequisite of origin and situation
      within the internal acoustic canal, have been discovered in the known literature
      since 1975. A further case was recently observed in our experience. The cases in
      the series showed no sex prevalence and in most of them the age of incidence was
      comprised between the fifth and sixth decade of life. Hearing loss was the
      prevalent symptom, lasting 1 month to 7 years before presentation.
      Myelocisternography, myelo-CT or high resolution CT/MR revealed no specific
      radiological features to distinguish small intrameatal meningiomas from the more
      frequently occurring vestibular schwannomas, while CT scan with bone algorithm
      could point out valuable indirect details for differential diagnosis. Various
      surgical approaches, i.e. middle fossa, translabyrinthine and retromastoid, were
      utilized by the different authors. RESULTS: Basing on apparent individual
      surgical preference, one of three different surgical routes (translabyrinthine,
      middle fossa, retromastoid) was chosen for 10 procedures in 9 patients. In all,
      except two cases the impression at surgery was of complete tumour removal.
      CONCLUSIONS: The possibility for meningiomas to recur and invade the surrounding
      bone requires a differential diagnosis from vestibular schwannomas. In the
      absence of intrinsic distinctive signs, radiological evaluation of peritumoral
      bone alterations could help diagnosis. Although the various surgical routes have
      often proved effective, temporal bone invasion justifies more extensive approach
      even in small tumours.

PMID- 10961495
TI  - Middle meningeal artery aneurysm associated with meningioma.
AB  - The aneurysms of the middle meningeal artery are extremely rare. 30
      pseudoaneurysms of the middle meningeal artery (MMA) are reported in literature.
      These are post-traumatic lesions different from the true aneurysms that have a
      different origin. In fact they can be associated with arteriovenous
      malformations, Paget's disease and tumors; nevertheless in some cases the genesis
      remains unknown. Sometimes the berry aneurysm of MMA can cause non traumatic
      extradural hematomas. The association meningioma-aneurysm of the middle meningeal
      artery is extremely rare: only a case has been signalled till now in literature.
      In our case the patient was a 69 year-old woman admitted in our department
      following an epileptic seizure. Neuroradiological studies (post-contrast CT and
      RM) showed a meningioma of the right pterion. A preoperative angiography
      evidenciated a big blush from the afferences of meningioma by the middle
      meningeal artery and, proximally a small berry aneurysm of this artery. Selective
      embolization of the tumor and the aneurysm was performed preoperatively with
      polyvinyl particles and straight platinum coils. A craniotomy a surgical
      resection of the meningioma were performed. The role of the endovascular
      treatment in the management of these lesions is underlined to decrease the risks
      of morbidity.

PMID- 10961496
TI  - Thalamic epidermoid cyst. A case report.
AB  - A case of thalamic epidermoid cyst is reported. Its clinical presentation,
      radiological, operative findings and histological findings are discussed.
      Intraparenchymal epidermoids are uncommon and to our knowledge only one case of
      thalamic epidermoid has been reported earlier. The literature is reviewed in
      regard to incidence, location and etiology of Intracerebral epidermoid tumor
      cysts.

PMID- 10961497
TI  - Spinal seeding of anaplastic ependymoma mimicking fungal meningitis. A case
      report and review of the literature.
AB  - BACKGROUND: The spinal seeding from brain tumors sometimes mimicks fungal
      meningitis on examination of cerebrospinal fluid. METHODS AND RESULTS: A 19-year
      old woman gradually developed increased intracranial hypertension. MRI identified
      a mass in the right parieto-occipital area. It was totally removed and
      histologically diagnosed as an anaplastic ependymoma. Radiation- and chemotherapy
      were administered postoperatively. The patient reported low back pain 5 months
      after the surgical treatment. MRI disclosed neither spinal dissemination nor
      tumor recurrence at the primary site. Lumbar puncture was performed and the
      cerebrospinal fluid (CSF) was found to have an extremely low glucose level (5
      mg/dl); no tumor cells were identified. Blood samples were obtained and a
      relative increase of WBC and CRP was noted. A slight degree of inflammation and
      low-grade fever were recorded. A tentative diagnosis of fungal meningitis was
      made and anti-fungal therapy was administered transventricularly and
      transvenously. However, her neurological condition continued to deteriorate
      gradually. Sequential CSF studies showed that the glucose level remained
      extremely low, it even decreased to 0 mg/dl Eight months after the surgical
      treatment, MRI with Gd-DTPA revealed marked subarachnoid enhancement in both
      intracranial and spinal areas. An open biopsy was performed and a histological
      diagnosis of intracranial and spinal seeding of the anaplastic ependymoma was
      returned. CONCLUSIONS: We report a patient with intracranial and spinal seeding
      of an anaplastic ependymoma that mimicked fungal meningitis. We discuss the
      difficulty of obtaining a differential diagnosis in this case and describe the
      mechanism of the decreased CSF glucose level.

PMID- 10961499
TI  - Gerhard schwarz: scientist and colleague

PMID- 10961498
TI  - Spinal cord compression due to multivel thoracic disc herniation: surgical
      decompression using a "combined" approach. A case report and review of the
      literature.
AB  - A case presenting with signs of spinal cord compression due to double contiguous
      thoracic disc herniation (TDH) is reported. A 66-year-old woman presented with a
      4-month history of intermittent episodes of weakness and numbness in the lower
      extremities, and urinary dysfunction. Six weeks prior to admission complete
      paraplegia developed. The diagnosis was established by MRI. Treatment consisted
      of complete excision of the herniated discs (T8-T9 and T9-T10) and decompression
      of the spinal cord with a right transpedicular approach combined with standard
      posterior approach. The postoperative course was uneventful, and the improvement
      was dramatic. We also include a review of other 39 case reports from the
      literature. This article highlights the importance of consideration of TDH when
      one deals with a case with an anterior mass causing spinal cord compression.

PMID- 10961500
TI  - Natural selection: a phase transition?
AB  - Information has two aspects: a quantity to be called 'extent' and a quality which
      may be termed 'content' since it deals with meaning. The latter originates via
      selective self-organization, which can be described also in quantitative physical
      terms. A prerequisite is the reproducibility of the informational substrate
      forming the basis of selection. This paper focuses on selection being the
      analogue of a physical phase transition. In Section 1 the criteria for phase
      transitions are formulated. Section 2 introduces the concept of information space
      and describes information as selected points or regions in this space. In Section
      3 selection is analyzed in terms of the criteria for phase transitions, and in
      Section 4 the concept is confronted with experimental data. The conclusion is
      reached that information content is generated via selection, which can be
      described as a phase transition in information space.

PMID- 10961501
TI  - The dielectric increments of aqueous polyelectrolyte solutions: a scaling
      approach
AB  - This paper deals with dielectric dispersion curves (covering a frequency range
      from a few Hz to 100 MHz) of Na-poly(styrene-sulfonate) of 65,000 < or = Mw < or
      = 1,060,000 g mol(-1) in aqueous solutions. The values of the low frequency
      (dielectric increment1) and high frequency (dielectric increment2) dielectric
      increments, obtained from the experimental curves matched to a superposition of
      two Cole-Cole equations, have been analyzed in terms of their concentration and
      molar mass dependence. The concentrations C (g l(-1)) of the various solutions
      were mostly situated in the transition regime defined by Odijk [T. Odijk,
      Macromolecules 12 (1979) 688] between the dilute regime (C < Cg*) and the semi
      dilute one (C > C**), and wherein the characteristic concentration C* marks the
      onset of flexibility effects on the polyion behavior. It has been shown that in
      the concentration range Cg* < C < C** the increments in both frequency domains
      satisfy a scaling relation dielectric increment(j) = Bj M(nu j) (C/C*)(mu j) with
      molar mass independent exponents nu j and mu j changing around C*. Their values
      are different for dielectric increment1 and dielectric increment2, except for mu
      above C* where both increments appear to become concentration-independent. Below
      Cg*, in the dilute regime, the two dispersion domains seem to merge. The
      increment dielectric increment = relative permittivity (0) - high frequency limit
      of relative permittivity is molar mass independent if scaled to (C/Cg*). The
      molar mass dependence of the increments as a function of the macromolecular
      concentration rhoP, dielectric increment or dielectric increment(j) approximately
      Mgamma (rhoP)mu, also reveals differences between the different concentration
      regimes. Extrapolation from above Cg* to zero concentration is thus unjustified.

PMID- 10961502
TI  - Functional immobilisation of the nicotinic acetylcholine receptor in tethered
      lipid membranes
AB  - The nicotinic acetylcholine receptor from Torpedo was immobilised in tethered
      membranes. Surface plasmon resonance was used to quantify the binding of ligands
      and antibodies to the receptor. The orientation and structural integrity of the
      surface-reconstituted receptor was probed using monoclonal antibodies,
      demonstrating that approximately 65% of the receptors present their ligand
      binding site towards the lumen of the flow cell and that at least 85% of these
      receptors are structurally intact. The conformation of the receptor in tethered
      membranes was investigated with Fourier transform infrared spectroscopy and found
      to be practically identical to that of receptors reconstituted in lipid vesicles.
      The affinity of small receptor ligands was determined in a competition assay
      against a monoclonal antibody directed against the ligand-binding site which
      yielded dissociation constants in agreement with radioligand binding assays. The
      presented method for the functional immobilisation of the nicotinic acetylcholine
      receptor in tethered membranes might be generally applicable to other membrane
      proteins.

PMID- 10961503
TI  - Understanding the function of bacterial outer membrane channels by reconstitution
      into black lipid membranes
AB  - Structural and functional information is obtained by the reconstitution of
      membrane channel forming proteins into black lipid membranes. Due to this
      outstanding sensitivity only little material is needed and single molecule
      detection can be easily achieved. An overview on different types of detection
      will be given.

PMID- 10961504
TI  - Influence of the effector peptide of MARCKS-related protein on actin
      polymerization: a kinetic analysis
AB  - The members of the MARCKS protein family, MARCKS (an acronym for myristoylated
      alanine-rich C kinase substrate) and MARCKS-related protein (MRP), interact with
      membranes, protein kinase C, and calmodulin via their effector domain, a highly
      basic segment composed of 24-25 amino acid residues. This domain is also involved
      in the interaction between MARCKS/MRP and actin. In this article we show that a
      peptide corresponding to the effector domain of MRP, the effector peptide,
      strongly influences the dynamics of actin polymerization. Depending on the
      stoichiometric ratio of effector peptide to actin the peptide either accelerates
      or retards the actin polymerization process, which takes place in the presence of
      near-physiological salt concentrations. A model is developed in which this
      phenomenon is explained by two independent nucleation processes involving free
      actin monomers and peptide-bound actin monomers, respectively. As a control, a
      possible regulatory mechanism has been investigated: we show that calmodulin
      inhibits the actin polymerizing activity of the MRP effector peptide, thereby
      validating our model approach.

PMID- 10961505
TI  - The unusually stable coiled-coil domain of COMP exhibits cold and heat
      denaturation in 4-6 M guanidinium chloride
AB  - A high thermal stability is observed for the five-stranded alpha-helical coiled
      coil domain of cartilage oligomeric matrix protein COMP. It does not unfold in
      non-denaturing buffer between 0 and 100 degrees C and thermal denaturation is
      only achieved at high concentrations of guanidinium chloride (4-6 M). In these
      solutions the protein structure is lost at decreasing (cold denaturation) and
      increasing temperatures (heat denaturation). In the cold denaturation region, the
      melting profile showed deviations from the theory of Privalov et al. [P.L.
      Privalov, V. Griko Yu, S. Venyaminov, V.P. Kutyshenko, Cold denaturation of
      myoglobin, J. Mol. Biol. 190 (1986) 487-498] probably due to deviations from a
      two-state mechanism. High thermal stability as well as cold and heat denaturation
      was also observed for a mutant of the coiled-coil domain of COMP in which
      glutamine 54 was replaced by isoleucine but it still forms pentamer. The melting
      temperatures in plain buffer for the heat denaturation of COMP coiled-coil domain
      and its mutant obtained by extrapolation to zero molar guanidinium chloride
      concentration are approximately 160 and 220 degrees C, respectively, which groups
      them among the most stable proteins.

PMID- 10961506
TI  - Binding of the antibacterial peptide magainin 2 amide to small and large
      unilamellar vesicles
AB  - The thermodynamics of binding of the antibacterial peptide magainin 2 amide (M2a)
      to negatively charged small (SUVs) and large (LUVs) unilamellar vesicles has been
      studied with isothermal titration calorimetry (ITC) and CD spectroscopy at 45
      degrees C. The binding isotherms as well as the ability of the peptide to
      permeabilize membranes were found to be qualitatively and quantitatively similar
      for both model membranes. The binding isotherms could be described with a surface
      partition equilibrium where the surface concentration of the peptide immediately
      above the plane of binding was calculated with the Gouy-Chapman theory. The
      standard free energy of binding was deltaG0 approximately -22 kJ/mol and was
      almost identical for LUVs and SUVs. However, the standard enthalpy and entropy of
      binding were distinctly higher for LUVs (deltaH0 = -15.1 kJ/mol, deltaS0 = 24.7
      J/molK) than for SUVs (deltaH0 = -38.5 kJ/mol, deltaS0 = -55.3 J/molK). This
      enthalpy-entropy compensation mechanism is explained by differences in the lipid
      packing. The cohesive forces between lipid molecules are larger in well-packed
      LUVs and incorporation of M2a leads to a stronger disruption of cohesive forces
      and to a larger increase in the lipid flexibility than peptide incorporation into
      the more disordered SUVs. At 45 degrees C the peptide easily translocates from
      the outer to the inner monolayer as judged from the simulation of the ITC curves.

PMID- 10961507
TI  - The phases of small networks of chemical reactors and neurons
AB  - We present an experimental study of the phase relationships observed in small
      reactor networks consisting of two and three continuous flow stirred tank
      reactors. In the three-reactor network one chemical oscillator is coupled to two
      other reactors in parallel in analogy to a small neural net. Each reactor
      contains an identical reaction mixture of the excitable Belousov-Zhabotinsky
      reaction which is characterized by its bifurcation diagram, where the electrical
      current is the bifurcation parameter. Coupling between the reactors is electrical
      via Pt-working electrodes and it can be either repulsive (inhibitory) or
      attractive (excitatory). An external electrical stimulus is applied to all three
      reactors in the form of an asymmetric electrical current pulse which sweeps
      across the bifurcation diagram. As a consequence, all three reactors oscillate
      with characteristic oscillation patterns or remain silent in analogy to the
      firing of neurons. The observed phase behavior depends on the type of coupling in
      a complex way. This situation is analogous to the in vivo measurements on single
      neurons (local neurons and projection neurons) performed by G. Laurent and co
      workers on the olfactory system of the locust. We propose a simple neural network
      similar to the reactor network using the Hodgkin-Huxley model to simulate the
      action potentials of the coupled single neurons. Analogies between the reactor
      network and the neural network are discussed.

PMID- 10961508
TI  - A Pro --> Ala substitution in melittin affects self-association, membrane binding
      and pore-formation kinetics due to changes in structural and electrostatic
      properties
AB  - Melittin, the main component of bee venom of Apis mellifera, contains a proline
      at position 14, which is highly conserved in related peptides of various bee
      venoms. To investigate the structural and functional role of Pro14 a melittin
      analogue was studied where proline is substituted by an alanine residue (P14A).
      The investigations were focussed on: (i) the secondary structure in aqueous
      solution and membranes; (ii) the self-association in solution; (iii) the binding
      to POPC membranes; and (iv) the P14A-induced leakage and pore formation in
      membrane vesicles. Circular dichroism and gel filtration experiments showed that
      P14A exists at concentrations < 12 microM in monomeric form with an alpha
      helicity of 28 +/- 7%. A further increase in peptide concentration leads to the
      formation of large aggregates consisting of 9 +/- 1 monomers. While binding
      studies with POPC vesicles revealed for P14A a stronger binding affinity towards
      membranes than for melittin, the peptide-induced leakage of fluorescent markers
      from vesicles was less efficient for P14A than for melittin. Furthermore, an
      unexpected efflux behaviour at high values of bound P14A was observed which
      indicated that the pore formation kinetics for P14A is more complex than it was
      reported for melittin. The different features of P14A in aggregation, binding and
      efflux compared to melittin are mainly ascribable directly to structural changes
      caused by the proline --> alanine substitution. Furthermore, the results indicate
      an improved screening of the positively charged residues of P14A by counterions
      which contributes additionally to the observed differences in peptide activities.
      It is suggested that the presence of proline in melittin is not only of
      structural importance but also influences indirectly the electrostatic properties
      of the native peptide.

PMID- 10961509
TI  - Bacteriorhodopsin: the functional details of a molecular machine are being
      resolved
AB  - The photon-driven proton translocator bacteriorhodopsin is considered to be the
      best understood membrane protein so far. It is nowadays regarded as a model
      system for photosynthesis, ion pumps and seven transmembrane receptors. The
      profound knowledge came from the applicability of a variety of modern biophysical
      techniques which have often been further developed with research on
      bacteriorhodopsin and have delivered major contributions also to other areas.
      Most prominent examples are electron crystallography, solid-state NMR
      spectroscopy and time-resolved vibrational spectroscopy. The recently introduced
      method of crystallising a membrane protein in the lipidic cubic phase led to high
      resolution structures of ground state bacteriorhodopsin and some of the
      photocycle intermediates. This achievement in combination with spectroscopic
      results will strongly advance our understanding of the functional mechanism of
      bacteriorhodopsin on the atomic level. We present here the current knowledge on
      specific aspects of the structural and functional dynamics of the photoreaction
      of bacteriorhodopsin with a focus on techniques established in our institute.

PMID- 10961510
TI  - Electroporation of curved lipid membranes in ionic strength gradients
AB  - A thermodynamic theory for the membrane electroporation of curved membranes such
      as those of lipid vesicles and cylindrical membrane tubes has been developed. The
      theory covers in particular the observation that electric pore formation and
      shape deformation of vesicles and cells are dependent on the salt concentration
      of the suspending solvent. It is shown that transmembrane salt gradients can
      appreciably modify the electrostatic part of Helfrich's spontaneous curvature,
      elastic bending rigidity and Gaussian curvature modulus of charged membranes. The
      Gibbs reaction energy of membrane electroporation can be explicitely expressed in
      terms of salt gradient-dependent contributions of bending, the ionic double
      layers and electric surface potentials and dielectric polarisation of aqueous
      pores. In order to cover the various physical contribution to the chemical
      process of electroporation-resealing, we have introduced a generalised
      chemophysical potential covering all generalised forces and generalised
      displacements in terms of a transformed Gibbs energy formalism. Comparison with,
      and analysis of, the data of electrooptical relaxation kinetic studies show that
      the Gibbs reaction energy terms can be directly determined from turbidity
      dichroism (Planck's conservative dichroism). The approach also quantifies the
      electroporative cross-membrane material exchange such as electrolyte release,
      electrohaemolysis of red blood cells or uptake of drugs and dyes and finally gene
      DNA by membrane electroporation.

PMID- 10961511
TI  - Dielectric spectroscopy of biological materials and field interactions: the
      connection with Gerhard Schwarz

PMID- 10961512
TI  - Reproducibility of diurnal variation in sub-maximal swimming.
AB  - Swimming training is characterised by the use of early morning and evening
      training sessions. The purpose of the present study was to investigate if the
      physiological and kinematic responses to swimming a typical training set are
      affected by time of day. Seven male collegiate swimmers (age 22 +/- 4 years;
      height 1.8 +/- 0.1 m; mass 82.1 +/- 4.1 kg) completed a standardised 600 m warm
      up followed by a 10 x 100 m sub-maximal freestyle set twice a day (06:30-08:00 h
      and 16:30-20:00 h) on three separate days. Swimming speed was controlled
      precisely throughout (limits of agreement multiplied/divided 1.00) using a new
      pacing device (Aquapacer, Challenge and Response, Inverurie, Scotland). Oral
      temperature (To), heart rate (HR), minute ventilation (VE), oxygen uptake (VO2),
      carbon dioxide expired (VCO2), respiratory exchange ratio (RER), capillary blood
      lactate (Bla), and glucose (BGL) were measured at rest and post exercise. Stroke
      rate (SR) and HR were measured during the first nine 100 m repetitions while rate
      of perceived exertion (RPE) was measured immediately after each 100 m.
      Significant diurnal variation was found at rest in To, HR, and VO2 on all three
      days and for VE and VCO2 on two of the days (P<0.05). During the training set no
      diurnal variation was evident in HR and SR responses or repetition times although
      RPE values were higher in morning trials compared to evening trials on two of the
      three days (P < 0.05). Post-exercise significant diurnal variation was found for
      To and blood glucose for two of the three days (P < 0.05). Therefore, although
      diurnal variation is evident at rest, there is no subsequent effect on
      physiological and kinematic responses during a sub-maximal training set following
      a standardised warm-up.

PMID- 10961513
TI  - Lactate transport in rat sarcolemmal vesicles after a single bout of submaximal
      exercise.
AB  - We investigated the effects of a single bout of non-exhaustive exercise (25 m x
      min(-1), 10% grade, for 30 min) on the initial rates of lactate uptake in rat
      skeletal muscle sarcolemmal vesicles and the monocarboxylate transporter 1 (MCT1)
      content in isolated hindlimb muscles in relation to the exercise-induced
      oxidative stress. The exercise led to a decrease in red gastrocnemius and red
      vastus lateralis muscle glycogen content by 74% and 83%, respectively, and an
      increase in blood lactate concentration from 1.67 +/- 0.15 to 3.44 +/- 0.47 mM (p
      < 0.05). Initial rates of lactate uptake were measured in zero-trans conditions,
      at pH 7.4, for 1, 10, 30 and 100 mM external lactate concentrations. Lactate
      transport capacity was significantly decreased at 1 mM in the exercised group (p
      < 0.05), while a non-significant trend towards an increase was observed at 10, 30
      and 100 mM. We failed to obtain any change in soleus, red tibialis anterior and
      white gastrocnemius muscle MCT1 content (p>0.05), and no evidence of exercise
      induced oxidative stress in terms of muscle malondialdehyde content and
      glutathione peroxidase and superoxide dismutase activities was observed after the
      30 min exercise bout. These results indicate that a single bout of submaximal
      exercise, which did not induce an increase in muscle MCT1 content and apparent
      oxidative stress, decreased lactate transport capacity at low physiological
      concentration. Although the changes are small and independent of a MCT1
      facilitated lactate transport regulation, we suggest that another MCT isoform
      with different kinetic properties from MCT1 could be present in the sarcolemma
      and responsible for lactate exchange alterations.

PMID- 10961514
TI  - Effects of differing heat and humidity on the performance and recovery from
      multiple high intensity, intermittent exercise bouts.
AB  - The aim of this study was to determine the effects of different conditions of
      heat and humidity on two multiple bouts of high intensity cycling with 60 min
      recovery between each bout. Eight males (age: 25.5+/-1.8 yr, height: 179.0+/-3.7
      cm; weight: 72.3+/-4.0 kg; VO2peak: 51.5+/-2.4 ml x kg(-1) x min(-1), Peak
      Aerobic Power: 366+/-13 W) volunteered for this study. After undertaking VO2peak
      testing, all participated randomly, in three consecutive 30 s Wingate tests in
      three different environmental conditions being: Normal (22 degrees C/30% RH), Wet
      (30 degrees C/85% RH), and Hot (40 degrees C/40% RH). Subjects were then
      monitored for the 60 min post-exercise period after which time they repeated the
      Wingate tests and were again monitored for 60 min. Blood samples were taken pre,
      immediately post exercise, and at 1, 5, 10, 15, 30, 45, and 60 min into each of
      the recovery periods and analysed for lactate, pH, and hematocrit. Heart rate was
      monitored continuously throughout exercise (5 s average) and recovery (60 s
      average). Weight was measured pre exercise and at 15, 30, 45, and 60 min post
      exercise. Urine samples were collected at the same time and analysed for
      osmolality. The results of the experiment indicated that environmental conditions
      had no effect on the performance of either series 1 or 2 Wingate tests. Neither
      were there any changes in weight throughout the three conditions or across the
      condition. Post exercise pH levels were lower than pre exercise values (p <
      0.0001) and the reverse was true for blood lactate levels (p < 0.0003). We
      conclude that anaerobic exercise is not unduly affected by hot or humid
      conditions when subjects can re-hydrate according to decreases in body weight.

PMID- 10961515
TI  - The effect of supraphysiological doses of anabolic androgenic steroids on
      collagen metabolism.
AB  - We examined the effect of supraphysiological doses of anabolic androgenic
      steroids (AAS) on collagen metabolism and whether the changes reflect the
      alterations in muscle, bone, and tendon collagen metabolism, possibly in a tissue
      specific manner. Serum carboxyterminal propeptide of type I procollagen (PICP),
      carboxyterminal telopeptide of type I collagen (ICTP), aminoterminal propeptide
      of type III procollagen (PIIINP), urine hydroxylysylpyridinoline (HP), and
      lysylpyridinoline (LP) as well as urine creatinine were determined from 17 men
      abusing AAS. Measurements were made twice during the intake of AAS and twice
      during the subsequent withdrawal period. When the volunteers were on steroids,
      their serum PIIINP concentrations and urine HP/LP ratio were significantly higher
      and their serum ICTP concentrations were significantly lower than during the
      withdrawal period (p < 0.05). Serum PIIINP correlated with total cumulative doses
      of injectable intramuscular steroids, and serum ICTP correlated with the duration
      of the steroid intake period (p<0.05). The results suggest that high doses of AAS
      decrease the degradation and seem to increase the synthesis of type I collagen.
      Furthermore, high doses of AAS are suggested to enhance soft tissue collagen
      metabolism on the basis of increased type III collagen synthesis and elevated
      HP/LP ratio during the steroid administration period. Although the tissue
      specific turnover of collagen of soft connective tissues remains unknown, the
      turnover of bone collagen seems not to change following the use of high doses of
      AAS, at least within the time interval of the present study.

PMID- 10961516
TI  - Anabolic steroids impair the exercise-induced growth of the cardiac capillary
      bed.
AB  - BACKGROUND: Concomitant application of anabolic-androgenic steroids and physical
      exercise can induce cardiac hypertrophy. These experiments investigate the still
      unknown response of the cardiac myocytes and capillaries to the combined
      influence of various anabolic steroids and muscular exercise. METHODS: Female SPF
      NMRI mice were divided into the following groups: a) sedentary control, b)
      exercise (treadmill running); c) sedentary receiving Dianabol; d) exercise +
      Dianabol; e) exercise + Oral-Turinabol. After 3 and 6 weeks the left ventricular
      papillary muscles were studied morphometrically. Evaluated variables: minimal
      myocyte diameter, number of capillaries around a single myocyte, capillary
      density and intercapillary distance. RESULTS: Only the anabolic steroids +
      exercise groups showed a mild myocyte hypertrophy. In contrast, only exercise
      alone caused a significant increase of the capillary density after both
      experimental periods; e.g. capillary density after 6 weeks (capillaries/mm2, mean
      values +/- standard deviation, p < 0.05): control (4,272 +/- 287), exercise (5411
      +/- 755), dianabol (4,004 +/- 333), dianabol + exercise (4,076 +/- 403), oral
      turinabol + exercise (4,053 +/- 306). Moreover, unlike all other regimens, only
      exercise alone shortened the intercapillary distance. Finally, exercise without
      drugs induced the greatest increase in the number of capillaries around a single
      myocyte. CONCLUSIONS: Anabolic steroids combined with exercise: 1) induce mild
      hypertrophy of the cardiac myocytes, 2) impair the cardiac microvascular
      adaptation to physical conditioning. The microvascular impairment may cause a
      detrimental alteration of the myocardial oxygen supply, especially during
      muscular exercise.

PMID- 10961517
TI  - Increase characteristics of the cumulated excess-CO2 and the lactate
      concentration during exercise.
AB  - The so-called excess-CO2 in physical exertion results stoichiometrically directly
      from the quantity of protons bound in bicarbonate buffering. This situation is
      used in determining the ventilatory threshold (VT). However, the extent to which
      the degree and increase characteristics of excess-CO2 can be used as an
      equivalent to blood lactate concentrations is uncertain. To investigate this
      relationship, 21 healthy men exercised on a cycle ergometer (starting at 50 watt,
      increases of 50 watt every 3 minutes) to subjective exhaustion. To evaluate the
      characteristics of this increase, a slope constant lambda was calculated in
      relation to performance for both the blood lactate concentration (lambda lactate)
      and the cumulated excess-CO2 (lambda CO2 excess). The start of the lactate
      increase (LT) and excess-CO2 (VT) showed good intercorrelation (VT=2.27+0.98 x
      LT; r=0.914; P<0.001). Mean lambda lactate and lambda CO2 excess were of similar
      dimensions in all subjects (69.3 +/- 39.8 watt vs. 80.11 +/- 15.7 watt), but a
      minority of the subjects (n=7) showed a considerably more gradual increase for
      the excess-CO2 to the maximum. Since in addition there was no significant
      correlation between the absolute values for maximum lactate concentrations and
      the cumulative excess-CO2, an interindividual prediction of lactate
      concentrations from the excess-CO2 would be difficult. It is an open question,
      however, whether perhaps additional performance-limiting factors, such as the
      ventilation or the buffering capacity, may be included when measuring the excess
      CO2 so that this parameter could be more a measure for the formation rate of new
      lactate than the blood lactate concentration alone.

PMID- 10961518
TI  - Montelukast does not affect exercise performance at subfreezing temperature in
      highly trained non-asthmatic endurance athletes.
AB  - Anti-leukotriene therapy represents a new principle in asthma treatment. As elite
      athletes can have asthma, this double-blind, placebo-controlled, randomised cross
      over study investigated the effect of 10 mg oral montelukast, a specific and
      potent cysteinyl leukotriene receptor antagonist, on physiological responses to
      submaximal and maximal aerobic exercise at -15 degrees C in 14 non-asthmatic
      highly trained endurance male athletes (maximal oxygen uptake [VO2 max] > 70 ml x
      kg(-1) x min(-1)). Heart rate, capillary blood lactate, minute ventilation with
      tidal volume and breathing frequency, respiratory exchange ratio and oxygen
      uptake were measured during the warm-up run of 10 min at 50%, runs of 10 min at
      90% and 5 min at 80% VO2max, and a timed run to exhaustion. Spirometry was
      performed at baseline, at four hours after tablet ingestion, after warm-up and
      exercise at 80% VO2max, and in the post exercise period. Compared to placebo,
      montelukast did not increase baseline FEV1, have a beneficial effect on
      physiological performance variables, or increase the mean (SD) running time to
      exhaustion (montelukast: 332.3 [45.8] s, placebo: 340.1 [53.3] s, P = 0.22).
      These findings do not suggest the need for disallowing the use of this drug by
      asthmatic athletes.

PMID- 10961519
TI  - Evolution of electromyographic signal, running economy, and perceived exertion
      during different prolonged exercises.
AB  - The purpose of this study was to compare the electromyographic (EMG) signal of
      the vastus lateralis muscle obtained during a run section of a triathlon and at
      the end of a prolonged run performed at the same running velocity. Seven subjects
      were studied on three occasions: a 2 h 15 min triathlon (30 min swimming, 60 min
      cycling, and 45 min treadmill running at 75% of the maximal aerobic speed), a 2 h
      15 min run, where the last 45 min (Prolonged Run, PR) were run at the same speed
      as the Triathlon Run (TR) on a motorized treadmill, and a 45 min Isolated Run
      (IR) performed at the same TR and PR velocity. The three experimental trials were
      randomised. Oxygen uptake (VO2), heart rate (HR), and EMG data were recorded
      during the three run sections. The results confirm a greater VO2 and HR during PR
      compared with IR (P<0.01) and TR (P<0.05). Also the VO2 values obtained during TR
      were significantly greater compared to IR (P < 0.05). EMG signal, obtained from
      the vastus lateralis muscle during 4 sec of isometric contraction at 35 % of
      maximal voluntary contraction (MVC), showed that after PR the mean power
      frequency (MPF) shifted significantly to lower frequencies (P<0.01) compared with
      MPF recorded before the prolonged run. Moreover, the signal amplitude (RMS) was
      increased significantly after PR in comparison to pre-trial (P < 0.01). Similar
      results were obtained for the TR at P < 0.05. The integrated EMG flow, QIEMG
      (iEMG/burst duration), recorded during all run sections, was significantly
      increased near the end of PR (i.e. 2 h 10 min of running) compared with QiEMG
      recorded after 1 h 30 min of running. No significant increase in QiEMG was
      observed with TR and IR situations. The results suggest that a long exercise bout
      of running led to a greater increase in muscle fatigue compared with a triathlon
      or an isolated run performed at the same running speed. In addition it is
      suggested that the rating of perceived exertion recorded during isometric
      contractions is a good indice to approach the level of fatigue during prolonged
      exercises.

PMID- 10961520
TI  - The effects of electromyostimulation training and basketball practice on muscle
      strength and jumping ability.
AB  - The aim of this study was to investigate the influence of a 4-week
      electromyostimulation training program on the strength of the knee extensors and
      the vertical jump performance of 10 basketball players. Electromyostimulation
      sessions were carried out 3 times weekly; each session consisted of 48
      contractions. Testing was carried out before and after the electromyostimulation
      training program (week 4) and once more after 4 weeks of normal basketball
      training (week 8). At week 4, isokinetic strength increased significantly (p <
      0.05) at eccentric and high concentric velocities (between 180 and 360 x s(-1));
      this was not the case for low concentric velocities (60 and 120 degrees x s(-1)).
      Electromyostimulation training increased also isometric strength at the two
      angles adjacent to the training angle (p < 0.01). Squat jump increased
      significantly by 14% at week 4 (p < 0.01), whereas counter movement-jump showed
      no change. At week 8, gains in isokinetic, isometric strength and squat-jump
      performance were maintained and the counter movement jump performance increased
      significantly by 17% (p<0.01). Electromyostimulation as part of a short strength
      training program enhanced knee extensor strength and squat jump performance of
      basketball players.

PMID- 10961521
TI  - Influence of different amounts of carbohydrate on endurance running capacity
      following short term recovery.
AB  - This study examined the effect of ingesting different amounts of carbohydrate
      (CHO) during 4 h recovery (REC) from prolonged running, on subsequent endurance
      running capacity when subjects were fully rehydrated. Nine men ran at 70% VO2max
      on a treadmill for 90 min (T1), followed by the REC and a run to exhaustion at
      the same speed (T2) on two occasions. Thirty minutes into REC, subjects ingested
      50 g of CHO from a 6.5% CHO-electrolyte solution (CE) on both occasions.
      Thereafter, subjects ingested either the same CE or a placebo (PL) every 30 min
      for the first 3 h of REC. The total volume ingested was equal to 150% of the body
      mass lost during T1 which achieved rehydration during REC in both trials. Higher
      blood glucose and serum insulin concentrations (P<0.05) were observed during REC
      in the CE trial. Nevertheless, similar run times were achieved during T2 in both
      trials (CE: 56.9+/-8.1 min and PL: 65.4+/-7.8 min) (+/- S.E.M) (NS). Therefore,
      these results suggest that ingestion of 50 g of CHO immediately after prolonged
      exercise, and rehydration with a placebo solution, results in a similar endurance
      capacity, after a 4 h recovery, as ingesting 3 times more CHO (approximately 167
      g CHO) over the same period.

PMID- 10961522
TI  - Pre-exercise glucose ingestion at different time periods and blood glucose
      concentration during exercise.
AB  - The purpose of this study was to investigate the effects of glucose ingestion
      (GI) at different time periods prior to exercise on blood glucose (BG) levels
      during prolonged treadmill running. Eight subjects (X+/-SD), age 20+/-0.5yr,
      bodymass 70.7+/-4.1 kg, height 177+/-4 cm, VO2max 52.8+/-7.8 ml x kg(-1) x min(
      1) who underwent different experimental conditions ingested a glucose solution (1
      g/kg at 350 ml) 30 min (gl-30), 60 min (gl-60), 90 min (gl-90), and a placebo one
      60 min (pl-60) prior to exercise in a counterbalanced design. Afterwards they ran
      at 65% of VO2max for 1 hour and then at 75 % of VO2max till exhaustion. Fingertip
      blood samples (10 microl) were drawn every 15 min before and during exercise for
      the determination of BG levels. Oxygen uptake (VO2), heart rate (HR), and blood
      lactate (La) were also measured every 15 min during exercise. Peak BG values were
      reached within 30 min after GI but were different (p < 0.01) at the onset of
      exercise (gl-30: 147+/-22, gl-60: 118+/-25, gl-90: 109+/-22, pl-60: 79+/-5mg/dl).
      The two-way ANOVA repeated measures and the Tukey post-hoc test revealed a higher
      BG concentration (p < 0.05) for the gl-30 and the pl-60 as compared to the gl-60
      and gl-90 during running (e.g. 15min run: 82+/-11, 68+/-5, 64+/-3, 78+/-7, and
      60min run: 98+/-12, 85+/-12, 83+/-11, 94+/-11 mg/dl for gl-30, gl-60, gl-90, and
      pl-60, respectively). However, this did not significantly affect the duration of
      treadmill running. The La levels were higher (p < 0.05) after GI as compared to
      placebo throughout exercise (values at exhaustion: 4.6+/-0.2, 5.0+/-1.5, 4.8+/-
      1.7 mmol/l for gl-30, gl-60, gl-90, and 3.5+/-0.8 mmol/l for placebo). The gl-30
      and the placebo fluctuated closer to normoglycaemic levels. The glucose ingestion
      (60 to 90 min) prior to exercise lowered the blood glucose levels without
      affecting the duration of running performance at 75% VO2max. Thus, in order to
      maintain normoglycaemic levels, pre-exercise glucose supplementation should be
      given 30 min before the onset of exercise.

PMID- 10961523
TI  - Hospitalization for primary varicella-zoster virus infection and its
      complications in patients from Southern Israel.
AB  - BACKGROUND: We conducted this study to determine the impact of chickenpox on two
      different ethnic populations in southern Israel: Jews and Bedouins. METHODS:
      Hospital records of 113 patients discharged from the Soroka Medical Center with
      the diagnosis of varicella during a 4.5-year period were reviewed. RESULTS: Mean
      age was 9.2 years and the average hospital stay was 5.4 days. Bacterial skin or
      soft tissue infections were the most common complications (30%), followed by
      pneumonia (17%) and central nervous system complications (11.5%). There were no
      fatal cases throughout the study period. The calculated hospitalization rate for
      varicella was one in every 319 cases. Major differences between Jews and Bedouins
      included an older mean age of Bedouin patients (13.9 years versus 4.5 years);
      higher hospitalization rate (relative risk [R.R.]: 2.8, 95% confidence interval:
      1.9-4.2), and higher risk for complicated varicella (R.R.: 2.1, 95% confidence
      interval: 1.3-3.4). CONCLUSION: Hospitalization of patients with varicella in
      southern Israel is common and varicella infection in Bedouins is associated with
      greater morbidity compared with that in Jews in southern Israel.

PMID- 10961524
TI  - Ethnic and geographic variations in the prevalence of hepatitis A, B and C among
      aboriginal villages in Hualien, Taiwan.
AB  - BACKGROUND: Taiwan is endemic for viral hepatitis infections. A field survey was
      performed in the isolated aborigines in Hualien, eastern Taiwan, to investigate
      the geographic and ethnic variations in hepatitis epidemiology. MATERIALS AND
      METHODS: From 1996 to 1998, blood was drawn from 1,748 subjects from two southern
      Ami and two northern Atayal villages for serum markers of hepatitis A, B and C.
      RESULTS: Hepatitis A infection approached 100% in all groups. Hepatitis B
      infection and carrier rates were higher in the Atayal than in the Ami (92.3% vs.
      49.1% and 20.8% vs. 5.3%; p<0.01). Hepatitis C infection rates were higher in
      three villages (27.5%, 20.1% and 25.4% vs. 3.6%; p<0.01). Hepatitis C infection
      increased with age (p<0.01) while hepatitis B infection did not. CONCLUSION:
      Hepatitis A infected most aborigines before the age of 15 years. Hepatitis B
      seldom infected people after the age of 15 years, while hepatitis C continued to
      infect people who were older. Geographic factors are important for hepatitis C
      infection, whereas for hepatitis B infection, in addition ethnicity is also
      important.

PMID- 10961525
TI  - Activity of cellular thymidine kinase 1 in PBMC of HIV-1-infected patients: novel
      therapy marker.
AB  - Cellular cytoplasmatic thymidine kinase 1 (TK1) catalyzes the intracellular
      phosphorylation of anti-HIV-1 nucleoside analogs zidovudine (AZT) and stavudine
      (d4T) to the corresponding monophosphate form. In HIV-1-infected patients,
      treated with combination therapy including one of these compounds for more than 1
      year, enzymatic activity of TK1 in peripheral blood mononuclear cells (PBMC) was
      determined by radioactive assay. TK1 activity in PBMC of HIV-1-infected patients
      correlated with CD4 cell count (r = 0.4, p<0.05) and HIV-1 RNA copy number (r =
      0.4, p<0.05), being lower in patients with decreased CD4 cell count and high
      viral load. Furthermore,TK1 activity differs between HIV-1-infected individuals
      treated for more than 6 months (13.5 pmol/mg/h) compared to patients treated for
      less than 6 months (28.1 pmol/mg/h; p<0.05) with chemotherapeutic agents
      including thymidine analogs. The results demonstrate that TK1 deficiency in PBMC
      of HIV-1 infected patients may develop due to continuous treatment with thymidine
      analogs and correlates with a more progressed stage of disease expressed as
      diminished CD4 cell count and increased viral load.

PMID- 10961526
TI  - In vitro activity of LY333328, a new glycopeptide, against extracellular and
      intracellular vancomycin-resistant enterococci.
AB  - The objectives of the study were to observe the activity of LY333328, a new
      semisynthetic glycopeptide, compared to that of vancomycin against six strains of
      Enterococcus faecium and Enterococcus faecalis, including four vancomycin
      resistant strains. Bacteria ingested by polymorphonuclear leukocytes (PMN) as
      well as extracellular bacteria were studied using a colony count method. The
      activity against intracellular bacteria was tested with the drugs present in the
      extracellular medium, as well as after preincubating the PMN and removal of the
      drugs. LY333328 is active against the tested enterococci, regardless of their
      susceptibility to vancomycin, with MICs of 1-2 mg/l. It is bacteriostatic against
      extracellular enterococci at concentrations of 2 microg/ml and above regardless
      of their resistance to vancomycin. After 4 h incubation at 10 MIC, vancomycin
      resistant strains of E. faecium and E. faecalis located intracellularly were
      reduced by 55% and 90%, respectively. Even after preincubation and removal of the
      drug, LY333328 had an effect at 10 MIC with a 20-30% reduction in the inoculum.
      The results suggest that in contrast to vancomycin, LY333328 is active against
      intracellular vancomycin-resistant enterococci, particularly E. faecalis, even
      after removal of the extracellular drug.

PMID- 10961527
TI  - Tropheryma whippelii DNA in saliva of patients without Whipple's disease.
AB  - Tropheryma whippelii is the causative agent of Whipple's disease, a difficult to
      diagnose systemic illness. Amplification of part of its 16S ribosomal RNA gene(s)
      has become a standard diagnostic method because of increased sensitivity as
      compared to classical histopathological analysis. Recently, we demonstrated the
      presence of T. whippelii DNA by PCR in duodenal biopsies and/or gastric juice of
      a considerable fraction of individuals without clinical signs of Whipple's
      disease. In this follow-up study, saliva and dental plaques of the same patients
      were screened for the presence of T. whippelii DNA. Six out of the 14 previously
      PCR-positive persons but none of the 17 controls had T. whippelii DNA in their
      saliva. Our results suggest that Whipple bacteria are ubiquitous environmental or
      commensal organisms causing Whipple's disease only in a particular subset of
      individuals, possibly those with an as yet uncharacterized immunological defect.

PMID- 10961528
TI  - Liposomal amphotericin B (AmBisome) in the treatment of neonatal candidiasis in
      very low birth weight infants.
AB  - AmBisome (2.5-7 mg/kg/day as a continuous 1 h infusion) was evaluated
      prospectively from September 1994 to January 1998 in 24 very low birth weight
      infants (mean birth weight 847+/-244 g, mean gestational age 26 weeks) with
      systemic candidiasis. Mean age at onset of candidemia was 17 days. One patient
      had two episodes of candidiasis. Thirteen infants failed previous antifungal
      therapy with amphotericin B (with or without 5-flucytosine). Candida spp. were
      isolated from the blood in all 25 episodes and from skin abscesses and urine in
      four infants each, respectively. There were 13 isolates of Candida albicans, ten
      of Candida parapsilosis, two of Candida tropicalis and one of Candida glabrata.
      One infant had a mixed infection with C. albicans and C. parapsilosis. The mean
      duration of therapy was 21 days; the cumulative AmBisome dose was 94 mg/kg.
      Fungal eradication was achieved in 92% of the episodes; mean duration of AmBisome
      therapy until achieving eradication was 9 days. Twenty (83%) infants were
      considered clinically cured at the end of treatment. No major adverse effects
      were recorded; one infant developed increased bilirubin and hepatic transaminases
      levels during therapy. Four (17%) infants died; in two of them (8%) the cause of
      death was directly attributed to systemic candidiasis. CONCLUSION: AmBisome
      represents an effective, safe and convenient antifungal agent in the therapy of
      systemic fungal infections in very low birth weight infants.

PMID- 10961529
TI  - Pneumocystis carinii pneumonia as a complication of immunosuppressive therapy.
AB  - BACKGROUND: Patients receiving immunosuppressive therapy with corticosteroids and
      cytotoxic agents may develop opportunistic infections such as Pneumocystis
      carinii pneumonia (PCP). This indicates a severe T-cell defect, but so far there
      are no established criteria for identifying patients at risk. PATIENTS AND
      METHODS: CD4+ and CD8+ T-lymphocyte counts were determined by flow cytometry in
      seven HIV-negative patients who developed PCP as a complication of
      immunosuppressive treatment. RESULTS: CD4+ T-lymphocyte counts (T-helper
      phenotype) were less than 200/microl in all seven patients (mean 90.6/microl).
      The markedly reduced CD4 counts measured in these patients are similar to those
      observed in organ transplant recipients who developed PCP during
      immunosuppressive therapy for prevention of graft rejection and in HIV-positive
      patients with PCP as an AIDS-defining illness. CONCLUSION: Measuring CD4+ T
      lymphocyte counts may be helpful in determining the risk of PCP not only in HIV
      positive patients, but also in patients receiving immunosuppressive therapy. The
      risk of acquiring PCP seems to increase when CD4+ lymphocyte counts drop below
      200/microl, regardless of the underlying disease.

PMID- 10961530
TI  - Association in the seroprevalence of hepatitis A and herpes simplex-1 viruses in
      young adults in Israel.
AB  - BACKGROUND: The rise in the standard of living of the Israeli population during
      recent decades has been accompanied by a significant decline in the prevalence of
      various viral diseases including hepatitis A (HAV). This trend is not reflected
      in the seroprevalence of herpes simplex (HSV) infection, which has remained
      stable during these years. MATERIALS AND METHODS: The Public Health Branch of the
      Israel Defense Force (IDF) Medical Corps continuously draws a systematic,
      representative sample of male and female recruits on their 1st day of service,
      based on digit combinations of the military identification number. These recruits
      are asked to give a blood sample and to undergo a short interview. A quantitative
      determination of anti-HSV-1 and anti-HAV antibodies was performed. RESULTS: In
      the present study that included 124 male and 98 female 18-year-old army recruits,
      51.1% of the anti-HSV-positive subjects was also positive for anti-HAV, compared
      to 27% among anti-HSV-negative persons. Rate ratio (RR) for anti-HAV
      seropositivity between anti-HSV-1-positive and negative recruits was 1.86 (95% CI
      1.3-2.7). CONCLUSION: The present study suggests a strong association between the
      seroprevalence of both viruses.

PMID- 10961531
TI  - IL-6 in CSF during ventriculitis in preterm infants with posthemorrhagic
      hydrocephalus.
AB  - Treatment of infants with posthemorrhagic hydrocephalus by diversion of CSF is
      frequently complicated by bacterial ventriculitis. We report the CSF values
      before and during bacterial ventriculitis of four very low birth weight infants
      with progressive posthemorrhagic ventricular dilatation. Extremely high CSF IL-6
      concentrations of between 8,000 and 61,000 pg/ml were observed and compared with
      values reported in the literature. IL-6 seems to be a useful marker for bacterial
      ventriculitis in preterm infants. The role of IL-6 monitoring in the CSF of
      preterm infants with posthemorrhagic hydrocephalus for early diagnosis of
      bacterial ventriculitis prior to clinical manifestation should be clarified by
      further studies.

PMID- 10961532
TI  - Disseminated adenovirus infection in two premature infants.
AB  - We present two premature infants with disseminated neonatal adenovirus infection,
      whose epidemiology, clinical course and outcome differ to a great extent. The
      first infant, born vaginally at 35 weeks gestational age after premature rupture
      of membranes and maternal illness, developed pneumonia, hepatitis and
      coagulopathy and died of circulatory failure at the age of 17 days. The other
      infant, delivered by cesarean section at 36 weeks gestational age, did - in
      contrast to all documented cases in the literature - not show any signs of
      pneumonia and survived meningitis without sequelae. The mode of transmission of
      the viral infection may have been via the maternal birth canal in the first
      infant and transplacental in the second one. Diagnosis was obtained by direct
      immunofluorescent test and serology in the first patient and by maternal serology
      and the detection of viral antigen in tracheal aspirates (ELISA) in the second
      patient. Disseminated neonatal adenovirus infection has a high mortality and
      should be considered in the differential diagnosis of neonatal sepsis, especially
      when pneumonia, hepatitis and neurologic symptoms develop together with
      thrombocytopenia or disseminated intravascular coagulopathy.

PMID- 10961533
TI  - Mycotic aneurysm of the aortic arch.
AB  - A 61-year-old diabetic woman presented with a mycotic aneurysm of the aortic
      arch, also involving the left subclavian and vertebral arteries, caused by
      Staphylococcus aureus. Two months before, she had suffered from staphylococcal
      septic arthritis in her left knee. The patient was treated with antibiotics and
      an emergency operation was performed involving aneurysm excision and in situ
      synthetic graft replacement. She died on the fourth postoperative day from
      hemorrhagic shock.

PMID- 10961534
TI  - CSF interleukin-6 in neonatal Citrobacter ventriculitis after meningitis.
AB  - An infant with neonatal severe Citrobacter koseri (formerly Citrobacter diversus)
      meningoencephalitis developed necrosis with multicystic regression of both
      hemispheres. The ventriculitis persisted over months in spite of antibiotic
      therapy. The treatment succeeded with cefotaxime in a high dose (300 mg/kg/day)
      without surgical intervention. The infant had been previously treated with
      cefotaxime (200 mg/kg/day) over 5 weeks. High levels of CSF interleukin-6 (IL-6)
      permitted to attribute persisting CSF pleocytosis in spite of sterile CSF
      cultures to chronic infection and not to reminiscence of brain necrosis. This
      report reveals two main points. On the one hand, the importance of therapy
      monitoring with IL-6 in CSF for the consequent treatment of Citrobacter
      meningitis and on the other hand, high-dose cefotaxime (300 mg/kg/day) treatment
      of Citrobacter ventriculitis, which succeeded without surgical intervention.

PMID- 10961535
TI  - Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral
      vasculitis.
AB  - An 18-year-old woman was admitted to hospital because of subcutaneous hematoma
      and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical
      antimicrobial treatment and induction chemotherapy were started. After initial
      defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan
      of the lung was consistent with an invasive fungal infection. Treatment with
      amphotericin B was started and antimicrobial treatment was continued with
      liposomal amphotericin B because of an increase in creatinine later. The fever
      persisted and the patient suddenly developed progressive neurological symptoms.
      CT scan of the head suggested cerebral infarction and angiography of the extra-
      and intracranial arteries showed signs of vasculitis. Six days after the onset of
      neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate,
      irregularly branched hyphae in various histologic sections including brain.
      Absidia corymbifera could be isolated from lung tissue confirming the diagnosis
      of disseminated mucormycosis. In this case, angiographic findings suggested
      severe cerebral vasculitis which was in fact caused by thromboembolic
      dissemination of fungal hyphae. This case underlines the fact that cerebral
      symptoms in febrile neutropenic patients are highly indicative for fungal
      infections of the brain.

PMID- 10961536
TI  - Scarlet fever associated with hepatitis--a report of two cases.
AB  - Infection with group A beta-hemolytic streptococci (GABHS) is the most common
      bacterial cause of acute pharyngitis and tonsillitis beyond infancy. We report on
      two patients with scarlet fever associated with hepatitis. The patients (boys
      aged 6 and 7 years) both presented with a scarlatiniform rash, dark urine and
      light-colored stools. Laboratory studies revealed elevated liver transaminases
      and negative antibody tests against hepatitis viruses A, B and C, cytomegalovirus
      and Epstein-Barr virus. Both patients were treated with antibiotics and recovered
      completely within a few days. Although the association between scarlet fever and
      hepatitis has been known for many decades, the pathogenesis is still unknown.
      Physicians treating patients with group A beta-hemolytic streptococcal infections
      should be aware of possible hepatic involvement.

PMID- 10961537
TI  - Avascular necrosis of the femoral head: a side effect of highly active
      antiretroviral therapy (HAART) in HIV patients?

PMID- 10961538
TI  - Fluoroquinolone-induced tendinopathy: also occurring with levofloxacin.

PMID- 10961539
TI  - Plasminogen activator inhibitor-1 fused with erythropoietin (EPO) mimetic peptide
      (EMP) enhances the EPO activity of EMP.
AB  - Erythropoietin (EPO) mimetic peptide (EMP) encoding sequence was inserted into
      the gene of plasminogen activator inhibitor-1 (PAI-1) between Ala348 and Pro349
      (P2'-P3'), generating a novel gene, PAI-1/EMP (PMP). This was cloned into pET32a
      expression vector, fused with TrxA peptide in the vector, and a 63-kDa protein
      was expressed in inclusion bodies with an expression level >50%. The TrxA/PMP
      protein was purified by Ni-NTA-agarose metal-ligand affinity chromatography to a
      purity >90%, showing a single, silver-stained band on SDS-PAGE. Using a
      reticulocyte counting assay, the EPO activity of PMP was determined to be 5,000
      IU/mg, 2,500-fold that of EMP.

PMID- 10961540
TI  - Nsc and Fmoc Nalpha-amino protection for solid-phase peptide synthesis: a
      parallel study.
AB  - The 2-(4-nitrophenylsulfonyl)ethoxycarbonyl (Nsc) group is an alternative to Fmoc
      for Nalpha-protection in solid-phase peptide synthesis. Nsc-amino acids may be
      particularly suitable for automatic synthesizers, in which the amino acids are
      stored in solution, and the incorporation of residues prone to racemization such
      as Cys and His. Owing to the hydrophilicity of the Nsc group, these derivatives
      are useful for the preparation of protected peptides in convergent solid-phase
      peptide synthesis strategies.

PMID- 10961541
TI  - Evaluation of new base-labile 2-(4-nitrophenylsulfonyl) ethoxycarbonyl (Nsc)
      amino acids for solid-phase peptide synthesis.
AB  - The 2-(4-nitrophenylsulfonyl)ethoxycarbonyl (Nsc) group is a new base-labile
      protecting group for solid-phase peptide synthesis, completely interchangeable
      with the fluorenylmethoxycarbonyl (Fmoc) protecting group, but with certain
      advantages. In this paper, we report a methodology with Nalpha-Nsc-protected
      amino acids for the synthesis of some melanotropins important to our research,
      namely, gamma-melanocyte-stimulating hormone (gamma-MSH), its [Nle3]-analogue,
      and a cyclic alpha-MSH/beta-MSH hybrid. We developed an efficient protocol for
      the synthesis of the cyclic MSH analogue that yielded this peptide in >98%
      purity. The gamma-MSH synthesis, which gave problems with both the Boc and Fmoc
      strategies, yielded the desired peptide by Nsc-chemistry but was accompanied by
      side products. Finally, the Nle3-gamma-MSH analogue was synthesized more
      efficiently using the Fmoc strategy, suggesting that Nsc-chemistry might not be
      the best methodology for certain sequences.

PMID- 10961542
TI  - A solid-phase synthetic strategy for the preparation of peptide-based affinity
      labels: synthesis of dynorphin A analogs.
AB  - Solid-phase synthetic methodology was developed for the preparation of peptide
      based affinity labels. The initial peptides synthesized were dynorphin A (Dyn A)
      analogs [Phe(p-X)4,D-Pro10]Dyn A(1-11)NH2 containing isothiocyanate (X=-N=C=S)
      and bromoacetamide (X=-NHCOCH2Br) groups. The peptides were assembled on solid
      supports using Fmoc-protected amino acids, and the side chain amine to be
      functionalized, Phe(p-NH2), was protected by the Alloc (allyloxycarbonyl) group.
      Following removal of the Alloc group by palladium(O), the reactive isothiocyanate
      and bromoacetamide functionalities were successfully introduced while the
      peptides were still attached to the resin. Synthesis of these peptides was
      carried out on polystyrene (PS) and polyethylene glycol-polystyrene (PEG-PS)
      resins containing the PAL [peptide amide linker, 5-(4-Fmoc-aminomethyl-3,5
      dimethoxyphenoxy)valeric acid] linker. Both the rate of Alloc deprotection and
      the purity of the crude affinity-labeled peptides obtained were found to be
      dependent on the resin used for peptide assembly.

PMID- 10961543
TI  - Syntheses of four peptides from the immunodominant region of hepatitis C viral
      pathogens using PS-TTEGDA support for the investigation of HCV infection in human
      blood.
AB  - Four peptides were designed and synthesized on a highly solvating copolymer of
      tetraethyleneglycol diacrylate cross-linked polystyrene (PS-TTEGDA) support with
      very high purity and yield. The polymer was synthesized in various cross-linking
      densities (1, 2, 3, 4, 5 and 10%) using radical aqueous suspension
      polymerization. Four per cent PS-TTEGDA resin showed rigidity and mechanical
      characteristics comparable with those of divinylbenzene cross-linked polystyrene
      (PS-DVB) support. Swelling and solvation characteristics of PS-TTEGDA were much
      higher than PS-DVB support in all solvents used in solid-phase peptide synthesis.
      Forty-eight hour treatment of the support with neat trifluoroacetic acid did not
      show any change in its infrared spectra. PS-TTEGDA could be functionalized with
      chloromethyl, aminomethyl and hydroxymethyl functional groups under various
      controlled conditions. Synthetic utility of the support was demonstrated by the
      synthesis of four peptides selected from the envelope and nonstructural protein
      region of the prototype hepatitis C virus (HCV). These peptides were later used
      successfully to develop a peptide-based immunoassay (PBEIA) for the detection of
      HCV immunity. Peptides designed from the NS1 and NS4 protein regions were found
      to be very promising for the development of a new diagnostic kit to detect HCV
      infection in human blood. Peptide purity was tested by RP-FPLC and the peptide
      identity was confirmed by amino acid analysis.

PMID- 10961544
TI  - Crystal structure of the low-humidity form of aspartame sweetener.
AB  - The low-humidity IB crystal form of aspartame (L-alphaaspartyl-L-phenylalanine
      methyl ester) is prepared via humidity-induced transition from the highly
      hydrated IA crystal form and is used widely as a sweetener. The crystal structure
      of the low-humidity IB form is determined at 1.05 A resolution (0.476 A(-1) in
      maximum sintheta/lambda) from an extremely fine fibrous crystal using synchrotron
      radiation. There are three aspartame molecules and two water molecules in the
      asymmetric unit of the monoclinic space group P2(1). Each aspartame molecule
      adopts an almost identical extended conformation which is commonly observed in
      other crystal forms of aspartame. Three aspartame molecules are assembled into a
      triangular trimer, and trimer units are stacked along the b-axis via hydrogen
      bonding and electrostatic interactions in the main chains and also via
      hydrophobic contacts in the phenyl side-chains. Six trimer units are related by
      pseudo 6(1)-screw axis symmetry and form a hydrophilic channel at their center.
      The hydrophilic channel in the IB form contains only four water molecules in the
      unit cell, compared with 16 in the IA form. Although the IB form exhibits a
      trimer structure similar to that of the IA form, one aspartame molecule is
      rotated by approximately equals 20 degrees from the orientation in the IA form.
      This arrangement of the molecule implies that the humidity-induced transition is
      accompanied by a flapping motion of its methyl ester group. These structural
      differences may imply the stepwise transition from the IA to the IB forms.

PMID- 10961545
TI  - Ligand-presenting assembly: a method for C- and N-terminal antigen presentation.
AB  - Achiral dicarboxylic acids were coupled with 2 eq. of the free alpha-amino groups
      of two fully side-chain protected peptide chains while these were still attached
      to a synthesis resin. Cleavage from the resin with simultaneous side-chain
      deprotection afforded two assembled peptide chains with free C-terminals.
      Suitable functionalization of the achiral dicarboxylic acid alternatively
      permitted continued peptide synthesis in a C to N orientation leading to a final
      peptide assembly which, after cleavage from the resin, may have multiple N to C
      and C to N presentation of one or more epitopes.

PMID- 10961546
TI  - The FESSH Diploma Examination in hand surgery. Federation of the European
      Societies for Surgery of the Hand.

PMID- 10961547
TI  - The history of hand surgery in Europe.

PMID- 10961548
TI  - Brain plasticity and hand surgery: an overview.
AB  - The hand is an extension of the brain, and the hand is projected and represented
      in large areas of the motor and sensory cortex. The brain is a complicated neural
      network which continuously remodels itself as a result of changes in sensory
      input. Such synaptic reorganizational changes may be activity-dependent, based on
      alterations in hand activity and tactile experience, or a result of
      deafferentiation such as nerve injury or amputation. Inferior recovery of
      functional sensibility following nerve repair, as well as phantom experiences in
      virtual, amputated limbs are phenomena reflecting profound cortical
      reorganizational changes. Surgical procedures on the hand are always accompanied
      by synaptic reorganizational changes in the brain cortex, and the outcome from
      many hand surgical procedures is to a large extent dependent on brain plasticity.

PMID- 10961549
TI  - Proximal fractures of the fifth metacarpal: a retrospective analysis of 25
      operated cases.
AB  - The clinical and radiological outcomes of 25 surgically treated fractures of the
      proximal third of the fifth metacarpal were retrospectively analysed. Many
      different methods of osteosynthesis were used. At follow-up after a mean of 3.3
      years, 15 of 25 patients had no pain. Most patients regained a nearly full range
      of motion in the adjacent joints and more than 90% of the contralateral grip
      strength. X-ray signs of degenerative arthritis in the metacarpohamate joint were
      observed in 10 of 25 patients. Pain was found to be directly correlated with the
      presence of degenerative changes.

PMID- 10961550
TI  - Clinical results of intraarticular fractures of the base of the fifth metacarpal
      treated by closed reduction and cast immobilization.
AB  - This retrospective study evaluated the results of closed reduction and cast
      immobilization for isolated intraarticular fractures of the base of the fifth
      metacarpal. Twenty-two of 37 such fractures were available for follow-up at an
      average of 43 months, and these had all healed at an average of 5 weeks without
      any cast complications. Twenty patients reported excellent or good results, and
      two reported fair or poor results. At follow-up, 13 had no arthrosis and nine had
      mild arthrosis of the carpometacarpal joint. However, outcome was not influenced
      by fracture type, the degree of subluxation or articular step off, or the
      presence of arthrosis. We conclude that isolated fractures of the base of the
      fifth metacarpal can be reliably treated with closed reduction and cast
      immobilization.

PMID- 10961551
TI  - The bilobed flap: a new application in the reconstruction of congenital thumb
      deviation.
AB  - Congenital radial angulation deformity of the thumb in Rubinstein-Taybi syndrome
      is generally corrected by a wedge osteotomy of the delta phalanx and a
      redistribution of the overlying skin using a Z-plasty or, rarely, skin grafting.
      We describe a new application of the bilobed flap in the reconstruction of the
      thumb and discuss its advantages over traditional methods in providing tension
      free skin cover, excellent access to the delta phalanx and aesthetically
      acceptable scars.

PMID- 10961553
TI  - Recurrent compressive neuropathy of the median nerve at the wrist: treatment with
      autogenous saphenous vein wrapping.
AB  - Recurrence of symptoms occurs in a significant number of patients after surgical
      decompression for carpal tunnel syndrome, and its management is both challenging
      and difficult. Fifteen patients with recurrent carpal tunnel syndrome were
      treated with a vein wrapping technique using the autologous saphenous vein. A
      total of 48 operations had been performed on these patients before wrapping the
      median nerve with a saphenous vein graft. At a mean follow-up of 43 months all
      patients reported significant pain relief and improvement in their sensory
      disturbances. Two-point discrimination and the findings of nerve conduction
      studies also improved.

PMID- 10961552
TI  - Primary vascularized distal radius bone graft for nonunion of the scaphoid.
AB  - A vascularized bone graft from the dorsoradial aspect of the distal radius was
      used with internal fixation to treat nonunion of the scaphoid in ten patients who
      had not received any previous surgical treatment. Five cases were classified as
      Lichtman type I and five as type II. The average age was 30 years (range, 18-40
      years). Associated avascular necrosis was observed in five cases. Postoperatively
      pain was relieved and union was achieved in all cases. The mean time to union was
      6.5 weeks. Range of motion, grip strength and pinch strength were also restored
      satisfactorily. These results suggest that this vascularized bone graft should be
      used as the primary procedure in Lichtman type I and II of scaphoid nonunions,
      regardless of the presence of avascular necrosis of the proximal pole.

PMID- 10961554
TI  - Effect of the Steindler procedure on the median nerve branches to the medial
      epicondylar muscles.
AB  - Usually the median nerve gives off six branches to the muscles arising from the
      medial epicondyle, which could be tightened during Steindler's procedure. We
      studied these branches before and after Steindler's procedure in 20 fresh
      cadavers and observed a considerable variation in the origin of the branches. The
      muscular branches arising from the median nerve did not seem to limit the
      mobilization of the medial epicondyle when performing Steindler's transfer. The
      limitation of the flexion observed after Steindler's procedure was mainly related
      to the tension of the transferred forearm flexor muscles. The variability of the
      origin of the branch to the flexor digitorum superficialis muscle could explain a
      lesion of this branch when Steindler's procedure is carried out with Brunelli's
      modification. The lateral transfer and the anterior transfer on to the humeral
      shaft did not influence the limitation of elbow flexion or result in tightness in
      any nerve branch to the transferred muscles.

PMID- 10961555
TI  - Variations of the posterior interosseous nerve.
AB  - The posterior interosseous nerves of 58 cadaver forearms of black South Africans
      were dissected to study their order of branching. In 43 specimens (74%), the most
      common order of branching was: extensor carpi radialis brevis; supinator;
      extensor digitorum; extensor carpi ulnaris; extensor digiti minimi; abductor
      pollicis longus; extensor pollicis brevis; extensor pollicis longus and extensor
      indicis. In 15 specimens (26%) different variations of the nerve were observed,
      some of which are reported for the first time. The knowledge of these variations
      could be useful during operations in the vicinity of the nerve, and when
      repairing a nerve injury or forecasting the location of a compressive lesion.

PMID- 10961556
TI  - Cancer incidence in patients treated surgically for Dupuytren's contracture.
AB  - Our aim was to study risk factors for Dupuytren's contracture (DC) by assessing
      cancer morbidity in a group of Swedish patients treated surgically for
      Dupuytren's contracture. The risk of cancer was determined in 15,212 patients
      operated on for Dupuytren's contracture, identified in the nationwide Swedish
      Inpatient Register during the period 1965 to 1994 by means of record linkage to
      the Swedish Cancer Register. Standardized incidence ratios (SIRs) were computed
      using age-, sex- and period-specific incidence rates derived from the entire
      Swedish population. The overall relative risk of cancer was increased by 24%.
      There were significantly increased risks for malignancies related to smoking such
      as buccal, oesophageal, gastric, lung and pancreatic cancers. Significantly
      increased risks were present for both prostate and rectal cancer in men and an
      increase risk for breast cancer in women was noted 1 year or more after surgery
      for Dupuytren's contracture. The present study confirms smoking and alcohol abuse
      as probable risk factors for DC. There are characteristics in patients with DC
      that alter the risks for other malignancies compared with the general population.

PMID- 10961557
TI  - The use of an in situ curing hydroxyapatite cement as an alternative to bone
      graft following removal of enchondroma of the hand.
AB  - Following curettage of enchondromata of the phalanges we filled the resultant
      bone cavity with hydroxyapatite cement in eight patients to avoid cancellous bone
      grafting. This material differs significantly from the ceramic hydroxyapatite
      commonly used in clinical practice. It is produced by the combination of two
      calcium phosphates which, in the presence of water, form a paste that cures to a
      solid implant with a microporous structure. Like ceramic hydroxyapatite, this
      cement is highly biocompatible and does not provoke a foreign body giant cell
      reaction, a sustained inflammatory response or a toxic reaction. We performed a
      prospective study with X-rays and clinical assessment up to 1 year after the
      operation. There were no complications, and all patients regained full function
      of the hand.

PMID- 10961558
TI  - Theoretical stress analysis in wrist joint--neutral position and functional
      position.
AB  - A three-dimensional rigid body spring model (3D-RBSM) was used to analyse force
      distribution through the wrist joint. In the neutral position, 48% of the force
      was transmitted through the radioscaphoid fossa, 40% through the radiolunate
      fossa, and 12% through the triangular fibrocartilage complex. In the functional
      position, the wrist joint was slightly extended, resulting in significantly
      increased force through the lunate (53%). The lunate appears to bear more load
      than has been reported previously.

PMID- 10961559
TI  - Reverse posterior interosseous flap based on an exteriorized pedicle to cover
      digital skin defects.
AB  - The posterior interosseous arterial flap is limited by its short vascular pedicle
      and proximal axis of rotation to the coverage of defects on the dorsal aspect of
      the hand and the first web space. The authors present the results of three cases
      in which these limits were surpassed by extending the wrist and exteriorizing the
      vascular pedicle, thus causing it to bowstring across the angle created by the
      extended wrist. When flap inset is complete the vascular pedicle is excised under
      local anaesthesia. This technique is an amalgamation of an island flap and a
      traditional pedicle flap and, as such, it is a two-stage procedure.

PMID- 10961560
TI  - Defatting of skin flaps using arthroscopic instruments--an effective alternative.
AB  - Defatting is often required when skin flaps are transferred to the hand. We
      present three patients with skin flaps which were defatted using an arthroscopic
      shaver and a standard suction device. There were no complications and all three
      patients were satisfied with their outcomes. This method provided an effective
      treatment for our patients and did not require the purchase of specialised
      equipment.

PMID- 10961561
TI  - Continuous postoperative catheter irrigation is not necessary for the treatment
      of suppurative flexor tenosynovitis.
AB  - The records of 75 patients admitted with pyogenic flexor tenosynovitis at two
      academic centers were reviewed. The functional outcomes of patients who received
      intraoperative irrigation only (n = 20) and those that had both intraoperative
      irrigation and continuous postoperative irrigation (n = 55) were compared. There
      were no statistically significant differences between the outcomes in the two
      groups.

PMID- 10961562
TI  - Mycobacterium kansaii flexor tenosynovitis presenting as carpal tunnel syndrome.
AB  - We present a case in which Mycobacterium kansasii flexor tenosynovitis caused the
      development of carpal tunnel syndrome. The diagnosis was made from synovial
      tissue specimens taken at the time of operation.

PMID- 10961563
TI  - Cervical outlet syndrome due to an accessory part of the trapezius muscle in the
      posterior triangle of the neck.
AB  - A 48-year-old man presented with pain and sensory impairment radiating from the
      neck to the thumb and forefinger of the right hand when lifting weights and
      turning or tilting the head. The symptoms were due to an anomalous accessory part
      of the trapezius muscle crossing the upper part of the brachial plexus. Excision
      of the anomalous muscle and release of the clavicular part of the
      sternocleidomastoid muscle abolished the complaints.

PMID- 10961564
TI  - Parosteal osteosarcoma of the ring finger metacarpal in a semi-professional
      pianist.
AB  - We report treatment of a low grade parosteal osteosarcoma of the ring finger
      metacarpal in a patient who would not contemplate ray amputation because of her
      career. Surgery involved excision of the bone, extracorporeal radiation then re
      implantation.

PMID- 10961565
TI  - Statistical modelling of general practice medicine for computer assisted data
      entry in electronic medical record systems.
AB  - Electronic medical record (EMR) systems have much potential, however, there are
      still a number of issues that need to be resolved before EMRs are widely
      accepted. One of these issues is the data input task, a potentially serious
      practical barrier to on-line medical computer usage. This paper reports the
      empirical modelling of data input requirements for physicians who use a problem
      orientated medical record system. Three statistical models (Bayesian conditional
      probability, multiple linear regression and discriminant analysis) to predict
      drug treatment given problem diagnoses are derived from EMRs of 2500 general
      Practice encounters. Two metrics are used to measure the predictive power of the
      models considering both the number of drugs correctly predicted and the strength
      with which the models predict them. The models are tested on 500 unseen records
      from the same patient-physician population and the data used to build the models.
      The Bayesian model produces the best predictions on unseen data and is also the
      easiest model to compute. A prototype interface that enables new patient cases to
      be entered is constructed to demonstrate how the predictive power of the model
      can translate into benefits in the data entry task.

PMID- 10961566
TI  - A three-tier clinical information systems design model.
AB  - Modern health care institutions are often multi-site organisations that implement
      heterogeneous information management systems interacting with distributed
      databases. Advances in treatment modality/technology and rapidly changing
      information technology create increasing demand for changes/redevelopment of many
      health information applications. These features spawn the need for solutions to
      (a) guarantee data exchange across different types of applications and database
      management systems, and (b) reduce the costs of systems development and
      modification. This paper explores the concept of 'middleware services' as a
      solution to achieve these goals. It reports on the successful application of a
      component-based 3-tier system architecture to develop a computerised clinical
      pathways management system. The implementation experience confirms a number of
      significant benefits of the 3-tier structure including, reusability, flexibility,
      significant reduction in costs and efforts of systems development, and provision
      of easy, open migration pathway for future change of technology and system
      redevelopment.

PMID- 10961568
TI  - CoMed: a real-time collaborative medicine system.
AB  - CoMed is a prototype of a real-time collaborative medicine system that allows
      medical specialists to share patient records and to communicate with each other
      on the Internet. CoMed consists of a multimedia medical database containing
      relevant information about laryngeal diseases and a real-time collaboration
      system including a teleconferencing system, a whiteboard and a chatting system.
      CoMed is web-based. We adopted the object database O2 and CORBA technologies for
      the multimedia medical database. Therefore, our system can provide the
      flexibility, extensibility and location transparency of patient databases. We
      developed a SeeYou Active X control for the teleconferencing system and a Java
      applet for the whiteboard and chatting system. CoMed improves the efficiency of
      the overall system by separating the servers on a UNIX machine and a Windows NT
      machine. CoMed can be utilized for stand-alone research, for collaborative
      consultations among medical specialists and for a telemedicine in participation
      with the patients and medical specialists. Our system can be extended easily into
      other types of the collaborative systems, such as collaborative distance
      learning, collaborative science system, etc.

PMID- 10961567
TI  - Implementation of an electronic medical record system in a pediatric
      psychopharmacology program.
AB  - The design, implementation, and utilization of an electronic medical record
      system (EMRS) in a pediatric psychopharmacology clinic is described. The EMRS is
      a relational database with information entered directly by the clinician during a
      patient visit. It has been used during more than 2590 patient visits with 805
      patients. Complete clinical documentation and simultaneous data entry as well as
      computer generated prescriptions for the patient were accomplished 75% of the
      time within a 20-min medication management session. One hundred consecutive
      parents of patients were asked to fill out a five-question survey to begin to
      assess the impact of the application. Of the 87 parents who responded, all (100%)
      noted that the doctor paid attention to their concerns. Between 88 and 90% of the
      parents reported that the use of the computer is a 'good' thing, made it easier
      to work with the doctor, and that they understood why the computer was being
      used. The findings support that the development and implementation of an EMRS
      with direct clinician information entry within pediatric psychopharmacology
      clinic, is feasible.

PMID- 10961569
TI  - WWW + smart card: towards a mobile health care management system.
AB  - This paper highlights the benefits of combining the World Wide Web and smart card
      technologies to support a highly mobile health management framework. In
      particular, we describe an approach using the SmartCard-Web Gateway Interface
      (SGI) as a common interface to communicate and access the medical records
      residing in a smart card. Importantly, by employing HTTP as the baseline protocol
      to access information on the smart card, SGI promotes the use of de facto
      standard web browsers as the common client user interface. The initial
      implementation of the framework has demonstrated the feasibility of the concept
      in facilitating a truly mobile access of patient's medical records based on SGI.

PMID- 10961570
TI  - The use of a medical dictionary for regulatory activities terminology (MedDRA) in
      prescription-event monitoring in Japan (J-PEM).
AB  - The Medical Dictionary for Regulatory Activities Terminology (MedDRA) version 2.1
      (V2.1) was released in March 1999 accompanied by the MedDRA/J V2.1J specifically
      for Japanese users. In prescription-event monitoring in Japan (J-PEM), we have
      employed the MedDRA/J for data entry, signal generation and event listing. In J
      PEM, the lowest level terms (LLTs) in the MedDRA/J are used in data entry because
      the richness of LLTs is judged to be advantageous. A signal is generated normally
      at the preferred term (PT) level, but it has been found that various reporters
      describe the same event using descriptions that are potentially encoded by LLTs
      under different PTs. In addition, some PTs are considered too specific to
      generate the proper signal. In the system used in J-PEM, when an LLT is selected
      as a candidate to encode an event, another LLT under a different PT, if any, is
      displayed on the computer screen so that it may be coded instead of, or in
      addition to, the candidate LLT. The five-level structure of the MedDRA is used
      when listing events but some modification is required to generate a functional
      event list.

PMID- 10961571
TI  - Clinical and practical requirements of online software for anesthesia
      documentation an experience report.
AB  - The aim of this paper is the presentation of a new version of the anesthesia
      documentation software, NarkoData, that has been used in routine clinical work in
      our department as part of an anesthesia information management system (AIMS)
      since 1995. The performance of this software is presented along with requirements
      for future development of such a system. The originally used version, NarkoData
      3.0, is an online anesthesia documentation software established by the software
      company ProLogic GmbH. It was primarily developed as a disk-based system for the
      MacOS operating system (Apple Computer Inc.). Based on our routine experience
      with the system, a catalogue of requirements was developed that concentrated on
      improvement in the sequence of work, administration and data management. In 1996,
      the concepts developed in our department, in close co-operation with medical
      personnel and the software company, led to a considerable enlargement of the
      program functions and the subsequent release of a new version of NarkoData. Since
      1997, more than 20 000 anesthesia procedures have been recorded annually with
      this new version at 115 decentralized work stations at our university hospital.

PMID- 10961572
TI  - Unambiguous identification of hospital patients: case study at the university
      departments of the General Hospital, Vienna.
AB  - This article considers the problem of identifying patients in one or more
      heterogeneous personal databases. The unambiguous identification of patients is
      an essential prerequisite for an efficient patient care system. We discuss the
      problems involved in this task and suggest how they can be dealt with. The
      solution of automatic consolidation of patient records sequires programming,
      organisational and work psychology measures. Following a survey of conventional
      identification methods, the method developed at the Department of Medical
      Computer Sciences, which is based on the current clinical situation at the
      General Hospital in Vienna (AKH--Allgemeines KrankenHaus), is described in
      detail. The basic principle is to identify patients unambiguously by means of an
      ID (IZAHL) derived directly from the personal data. Thereby a deterministic
      technique without probability weighting is used-all compared information must
      correspond completely. The article closes with a critical survey of experience
      gathered to date.

PMID- 10961573
TI  - Methods for selection of adequate neural network structures with application to
      early assessment of chest pain patients by biochemical monitoring.
AB  - A methodology for selecting, training and estimating the performance of adequate
      artificial neural network (ANN) structures and incorporating them with algorithms
      that are optimized for clinical decision making is presented. The methodology was
      applied to the problem of early ruling-in/ruling-out of patients with suspected
      acute myocardial infarction using frequent biochemical monitoring. The selection
      of adequate ANN structures from a set of candidates was based on criteria for
      model compatibility, parameter identifiability and diagnostic performance. The
      candidate ANN structures evaluated were the single-layer perceptron (SLP), the
      fuzzified SLP, the multiple SLP, the gated multiple SLP, the multi-layer
      perceptron (MLP) and the discrete-time recursive neural network. The
      identifiability of the ANNs was assessed in terms of the conditioning of the
      Hessian of the objective function, and variability of parameter estimates and
      decision boundaries in the trials of leave-one-out cross-validation. The commonly
      used MLP was shown to be non-identifiable for the present problem and available
      amount of data, despite artificially reducing the model complexity with use of
      regularization methods. The investigation is concluded by recommending a number
      of guidelines in order to obtain an adequate ANN model.

PMID- 10961574
TI  - Plasma kallikrein/kinin system: a revised hypothesis for its activation and its
      physiologic contributions.
AB  - Recent studies indicate that assembly of high molecular weight kininogen on its
      multiprotein receptor allows for prekallikrein activation. On endothelial cells,
      factor XII activation is secondary to prekallikrein activation and amplifies it.
      The immediate consequence of plasma prekallikrein activation is the cleavage of
      high molecular weight kininogen (HK) with liberation of bradykinin. Cleaved high
      molecular weight kininogen is antiangiogenic. Bradykinin stimulates tPA
      liberation and nitric oxide formation. In addition, formed plasma kallikrein
      promotes single-chain urokinase activation and subsequent plasminogen activation.
      Kininogens and their breakdown products also are antithrombins. The angiotensin
      converting enzyme breakdown product of bradykinin prevents canine coronary
      thrombosis. The author presents a new hypothesis for physiologic assembly and
      activation of the plasma kallikrein/kinin system and discusses its influence on
      vascular biology.

PMID- 10961575
TI  - Role of blood coagulation factor XI in downregulation of fibrinolysis.
AB  - Factor XI is a component of the intrinsic pathway of coagulation. A deficiency of
      factor XI is associated with a mild to moderate bleeding disorder especially from
      tissues with a high local fibrinolytic activity. In contrast, high levels of
      factor XI are a risk factor for venous thrombosis. The recent finding that factor
      XI can be activated by thrombin led to a revised model of coagulation. In this
      model the primary thrombin generation that results in fibrin formation takes
      place via the extrinsic pathway. Additional thrombin generation takes place
      inside the fibrin clot via the intrinsic pathway after the activation of factor
      XI by thrombin. High concentrations of thrombin are formed that are necessary for
      the activation of thrombin activatable fibrinolysis inhibitor (TAFI). Activated
      TAFI protects the fibrin clot against lysis. The role of factor XI in hemostasis
      can therefore be seen as a combination of procoagulant and antifibrinolytic
      actions. The new insights in the role of factor XI in coagulation and
      fibrinolysis may lead to new strategies for the treatment of thrombotic
      disorders.

PMID- 10961576
TI  - Circulating tissue factor and thrombosis.
AB  - Tissue factor (TF) on circulating microparticles has recently received much
      attention as a factor in myocardial infarction. We have developed systems by
      which we have been able to investigate the thrombogenic potential of blood-borne
      TF. Thrombi develop when native human blood is passed over either collagen-coated
      glass slides or over pig arterial media. These thrombi immunostain for TF even
      when the substrate contains none. Moreover, we have demonstrated that the
      deposited TF is active because the thrombi contain fibrin; fibrin deposition and
      thrombotic mass are both inhibited by the inclusion of a potent TF-inhibitor in
      the perfusions. We have also shown that leukocyte-derived particles attach to
      platelets in a reaction mediated by adhesion proteins.

PMID- 10961577
TI  - von Willebrand factor and thrombotic thrombocytopenic purpura.
AB  - Recent advances in the understanding of platelet-dependent hemostasis and von
      Willebrand factor (vWF) functional regulation offer new insights into the
      pathogenesis of thrombotic microangiopathic disorders. The discovery of vWF
      cleaving protease activity in normal plasma, and its deficiency in thrombotic
      thrombocytopenic purpura (TTP) patients, provides additional support for a
      pathologic role of ultra-large vWF in TTP. Although vWF-cleaving protease
      deficiency is highly prevalent among TTP patients, the defect has also been
      detected in individuals without active TTP. Therefore, vWF-cleaving protease
      deficiency appears to be an important risk factor for thrombotic microangiopathy
      rather than a specific diagnostic marker of TTP. Recent data indicate that vWF
      cleaving protease activity correlates with clinical parameters in thrombotic
      microangiopathy patients. Therefore, determination of vWF-cleaving protease
      activity might prove useful in the future care of thrombotic microangiopathy
      patients and might be a rational basis for future classification of thrombotic
      microangiopathic disorders.

PMID- 10961578
TI  - Platelet glycoprotein polymorphisms as risk factors for thrombosis.
AB  - Both blood platelets and genetics contribute to the development of acute ischemic
      arterial diseases. A careful analysis of the various clinical association studies
      supports a modest increased risk for coronary artery disease events in carriers
      of the PIA2 polymorphism of GPIIIa. Investigations with both platelets and stable
      cells lines have shown the PIA2 polymorphism is prothrombotic. Only a handful of
      studies have been performed for platelet GPla (integrin alpha2) and GPIb-IX-V,
      but there is support for the 807 T/C polymorphism of GPIa and the met145 and VNTR
      B/C genotype of GPIbalpha as risk factors in younger age groups. And isolated
      reports suggest other platelet polymorphisms (GPIIb, FcgammaRIIa, P-selectin,
      alpha2 adrenergic receptor, transforming growth factor [TGF]beta) are risk
      factors for arterial disease or produce a prothrombotic phenotype. Platelet
      glycoprotein polymorphisms should be added to the list of genetic risk factors
      for arterial thrombosis, particularly in younger patients and women.

PMID- 10961579
TI  - Inherited thrombophilia and fetal loss.
AB  - Acquired thrombophilia is a well-established cause of pregnancy loss. Increasing
      numbers of recent observations suggest that inherited thrombophilia is not only
      associated with gestational thromboembolism but is also a major cause of fetal
      loss. This review focuses on association of fetal loss with inherited
      thrombophilias, including dysfibrinogenemia and protein C, protein S, and
      antithrombin III deficiencies. Activated protein C resistance and factor V Leiden
      mutation are frequent causes of pregnancy loss. Thrombophilic states such as
      factor V Leiden and hyperhomocysteinemia may also play a role in other
      gestational vascular complications, including intrauterine growth restriction,
      preeclampsia, and placental abruption. Preliminary reports suggest that
      antithrombotic therapy may be of value in this setting. The potential application
      of antithrombotic modalities to prevent fetal loss in women with thrombophilia is
      discussed.

PMID- 10961580
TI  - D-dimer for the diagnosis of venous thromboembolism.
AB  - D-dimer, a breakdown product of cross-linked fibrin has been extensively
      evaluated as a diagnostic test for acute venous thromboembolism. Rapid, highly
      sensitive D-dimer assays are now available that are suitable for testing in the
      emergency setting. Preliminary studies suggest that when using a highly sensitive
      D-dimer assay, a negative test result may,be sufficient to exclude the diagnosis
      of venous thromboembolism without need for further testing. Less sensitive, but
      more specific D-dimer assays are also available. The negative predictive value of
      these latter assays is insufficient to exclude venous thromboembolism on the
      basis of a negative test result alone. However, their utility is increased by
      identifying patient populations at low risk for venous thromboembolism using
      consideration of clinical probability or radiographic testing. Further, large
      multicenter management studies are required to confirm the safety of relying on a
      negative D-dimer result to exclude the diagnosis of venous thromboembolism.

PMID- 10961581
TI  - Long-term treatment for venous thromboembolism.
AB  - Anticoagulation is the corner stone of therapy for venous thromboembolism. The
      optimal duration of this therapy depends on the balance between the risk of
      recurrent thrombosis if anticoagulants are stopped, and the risk of bleeding if
      patients remain on treatment. The risk of recurrence is low if thrombosis was
      precipitated by a major reversible risk factor such as surgery. Patients with
      idiopathic thrombosis (no apparent risk factor) and those with persistent risk
      factors (eg, cancer), have a high risk of recurrence. Some hereditary (eg,
      protein C, protein S or antithrombin deficiency; homozygous factor V Leiden) and
      acquired (eg, antiphospholipid antibodies) thrombophilic states are also risk
      factors for recurrence. Three months of anticoagulation is recommended when the
      risk of recurrence is low, whereas the duration of therapy should be extended to
      6 months or longer when this risk is high, depending on the balance between the
      risk of recurrence and the risk of bleeding in each individual patient. Heparin
      preparations, at doses intermediate to those used for the acute treatment of
      venous thromboembolism and for primary prophylaxis, are an alternative to oral
      anticoagulants during the maintenance phase of treatment.

PMID- 10961582
TI  - Antithrombotic treatments in acute ischemic stroke.
AB  - Ischemic stroke results most commonly from cerebral arterial thrombosis.
      Antithrombotic agents can reduce the incidence of cerebral embolic events or the
      extent of tissue injury and neurological outcome. The antiplatelet agents
      aspirin, ticlopidine, and the combination of dipyridamole and aspirin are
      associated with a significant reduction in second focal cerebral ischemic events.
      Oral anticoagulants have a role to reduce the incidence of cardiogenic emboli in
      patients with mechanical cardiac valves or nonvalvular atrial fibrillation. Both
      antithrombotics are untested in the acute setting. The recombinant tissue
      plasminogen activator rt-PA has been shown to significantly increase the number
      of stroke patients with no or minimal deficit when treated within 3 hours of
      symptom onset. Additional studies of this and other plasminogen activators by
      both intravenous and intra-arterial delivery have highlighted limitations to this
      approach, but also support its role in acute intervention. The risk of
      intracerebral hemorrhage attends the use of all antithrombotic agents, most
      notably plasminogen activators. Strategies to decrease this risk are likely to
      add to beneficial outcome.

PMID- 10961583
TI  - Antiphospholipid syndrome: antibodies and antigens.
AB  - Elucidation of the antibodies and antigens involved in the antiphospholipid
      syndrome has provided many new insights and research opportunities. The major
      autoantibodies associated with the syndrome and detected in clinical laboratory
      assays for antiphospholipid antibodies are directed against prothrombin and beta2
      glycoprotein I beta2GPI), a phospholipid-binding plasma protein whose
      physiological function is unknown. Recent advances in our understanding of these
      antibodies and antigens include discovery of the crystal structure of beta2GPI,
      identification of a plasmin cleavage site in beta2GPI, genetic studies of
      beta2GPI polymorphisms, development of clinical laboratory assays using purified
      protein antigens, and the identification of antigen specific T cells.

PMID- 10961584
TI  - Antiphospholipid syndrome: insights from animal models.
AB  - Animal models of the relatively new antiphospholipid syndrome (APS) enabled
      researchers to understand disease pathogenesis and to test novel experimental
      therapeutic modalities. Animal models of APS include spontaneous genetic models
      and experimental induced models. The latter test more reliably the pathogenicity
      of antiphospholipid antibodies because the syndrome is induced in normal mice
      rather than being secondary to a preexisting autoimmune disease. Reports about
      animal models of APS in the recent year provide new insights into the
      pathogenesis of antiphospholipid antibodies and beta2-glycoprotein-I in
      reproductive failure, neurologic manifestations, thrombosis, and atherosclerosis.
      In addition, novel therapies that were successful in experimental APS included
      anti-idiotypes, oral tolerance, and specific peptides that bind to beta2
      glycoprotein-I. Animal models provide the first step in development of novel
      therapies for patients with APS.

PMID- 10961586
TI  - Bibliography. Current world literature. Hemostasis and thrombosis.

PMID- 10961585
TI  - Catastrophic antiphospholipid syndrome.
AB  - In its classic presentation, the antiphospholipid syndrome manifests a
      combination of venous or arterial thrombosis and fetal loss, accompanied by
      elevations of antibodies directed toward negatively charged phospholipids, as
      measured by anticardiolipin antibody assays and/or positive lupus anticoagulant
      tests. The manifestations often include a moderate thrombocytopenia and, less
      commonly, hemolysis. In contrast, a less frequently encountered subset of the
      antiphospholipid syndrome, termed the "catastrophic" antiphospholipid syndrome,
      affects mainly small vessels predominantly supplying organs. The thrombocytopenia
      is usually marked, and a Coombs positive microangiopathic-type anemia may
      accompany the condition. Features of disseminated intravascular coagulation may
      be evident in some patients. It is fatal in approximately 50% of cases reported.
      Treatment should include not only adequate anticoagulation with intravenous
      heparin but also full doses of intravenous corticosteroids, to offset the
      systemic inflammatory response syndrome that occurs as a result of the extensive
      tissue damage, and plasmapheresis, using fresh frozen plasma. Parenteral
      antibiotics should be administered early if infection is suspected.

PMID- 10961587
TI  - Pouchitis is associated with mucosal imbalance between interleukin-8 and
      interleukin-10.
AB  - BACKGROUND: Mucosal lesions of pouchitis are characterized by a neutrophil
      infiltrate. Interleukin (IL)-8 is the main mediator involved in neutrophil
      recruitment and is down-regulated by IL-10. AIM: To look for an imbalance between
      IL-8 and IL-10 in patients with pouchitis. PATIENTS/METHODS: 18 patients having
      an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis
      defined by the pouchitis disease activity index of > or =7 points and 7 had no
      history of pouchitis. Biopsies taken at the site of inflammation or in the normal
      mucosa were scored for the histologic lesions, the intensity of neutrophil
      infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA
      were quantified by competitive polymerase chain reaction. RESULTS: IL-8, IL-10,
      and IL-10/IL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA
      levels were significantly higher in patients with a histologic score >2 (p =
      0.01) and in patients with crypt abscesses (p = 0.01). IL-10/IL-8 mRNA was
      significantly lower in patients having a histologic score >2 (p = 0.019), a
      neutrophil infiltration > or =10% (p = 0.013), and crypt abscesses (p = 0.01).
      CONCLUSION: Histologic lesions of pouchitis are associated with a mucosal
      imbalance between IL-8 and IL-10. IL-10 could be proposed as a new treatment for
      pouchitis.

PMID- 10961588
TI  - Exclusion of linkage of Crohn's disease to previously reported regions on
      chromosomes 12, 7, and 3 in the Belgian population indicates genetic
      heterogeneity.
AB  - Susceptibility to inflammatory bowel disease (IBD) is significantly determined by
      genetic factors. Linkage data from genome-wide searches have identified regions
      on chromosomes 16, 12, 7, and 3. Our goal was to replicate these four regions in
      a Belgian population of IBD families. Fifty-four IBD families were studied (47
      with Crohn's disease [CD] and 7 with mixed CD and ulcerative colitis, containing
      79 affected sibpairs (68 CD only, 11 mixed) for the regions previously implicated
      to chromosomes 16, 12, 7, and 3. In this study, no evidence for linkage was found
      on any of the four chromosomal regions studied for either the whole IBD dataset
      or the CD subgroup. The multipoint maximum logarithm of odds scores were less
      than 0.7 for all four regions. Exclusion mapping could significantly exclude
      chromosomes 3, 7, and 12. Despite earlier findings, we could significantly
      exclude linkage of CD with previously reported regions on chromosomes 12, 7, and
      3, and could not find evidence for linkage to chromosome 16. It is important to
      report these findings in light of the genetic heterogeneity of IBD. A genome-wide
      search on a larger group of affected siblings is being analyzed to detect other
      possible susceptibility loci in the Belgian population.

PMID- 10961590
TI  - Quality of life rapidly improves with budesonide therapy for active Crohn's
      disease. Canadian Inflammatory Bowel Disease Study Group.
AB  - Our aims were to assess the impact on health-related quality of life (HRQOL) of a
      controlled ileal release (CIR) formulation of budesonide in active Crohn's
      disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel
      Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was
      conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5
      mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes
      were compared among groups. Correlations for IBDQ and Crohn's Disease Activity
      Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over
      placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups
      (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were
      also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group.
      Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4).
      Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p <
      0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not
      response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL
      in active CD.

PMID- 10961589
TI  - Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+ T
      cells.
AB  - The objectives of this study were to quantify colonic cytokine and endothelial
      cell adhesion molecule (ECAM) expression in the colons of severe combined
      immunodeficient (SCID) mice reconstituted with different subsets of CD4+ T
      lymphocytes. We found that animals injected with CD45RBhigh but not CD45RBlow T
      cells or phosphate-buffered saline (PBS) developed clinical evidence of colitis
      at 6-8 weeks following reconstitution, as assessed by loss of body weight,
      development of loose stools and/or diarrhea, and histopathology. Concurrent with
      the onset of distal bowel inflammation was enhanced expression of a variety of
      Th1 and macrophage-derived cytokines including interferon gamma, tumor necrosis
      factor-alpha, interleukin (IL)-1beta, IL-6, IL-12, and IL-18 lymphotoxin-beta. In
      addition, message levels and vascular surface expression of ICAM-1, VCAM-1, and
      MAdCAM-1 were all significantly enhanced in the colitic SCID mice reconstituted
      with CD45RBhigh T cells compared with SCID mice reconstituted with PBS or
      CD45RBlow T cells that did not develop disease. Significant increases in some of
      these ECAMs were also noted in the cecum and stomach and to a lesser degree in
      the small bowel. Our data confirm that reconstitution of SCID mice with
      CD45RBhigh but not CD45RBlow T cells induces chronic colitis, and that the
      colonic inflammation is associated with enhanced expression of proinflammatory
      cytokines and different ECAMs in the colon. Furthermore, our studies demonstrate
      that reconstitution of SCID mice with CD45RBhigh T cells enhances ECAM expression
      in tissues distant from the site of active inflammation.

PMID- 10961591
TI  - Toxic pseudomembranous colitis in a patient with ulcerative colitis.
AB  - Toxic colitis is a severe disease that may be caused by several inflammatory
      and/or infectious diseases. Ulcerative colitis is one of the most frequent causes
      of toxic colitis in the United States. Toxic megacolon complicating Clostridium
      difficile colitis is a rare occurrence with significant morbidity and mortality.
      CASE REPORT: A 52-year-old male presented with rectal bleeding and tenesmus. He
      had been treated for amebiasis with metronidazole, and had improved. Two weeks
      later, symptoms recurred, and he was referred to our hospital. A sigmoidoscopy
      and biopsies demonstrated mucosal ulcerative colitis. He underwent treatment with
      systemic prednisone, mesalamine, and hydrocortisone enemas with adequate
      response. He was asymptomatic for 2 months, but later presented with a tender
      abdomen and rectal bleeding. Plain abdominal and thorax films showed colonic
      distention and free intraperitoneal air. Emergency laparotomy was performed, and
      an inflamed and distended colon, with free inflammatory liquid in the peritoneum,
      was found. A total abdominal colectomy with temporary ileostomy and Hartmann's
      pouch was performed. The histopathology analysis demonstrated a Clostridium
      difficile pseudomembranous colitis. CONCLUSION: The presence of toxic megacolon
      due to Clostridium difficile in patients with ulcerative colitis is a rare
      complication that may be suspected in patients with initial relapse who are on
      antibiotics.

PMID- 10961592
TI  - Apoptosis: implications for inflammatory bowel disease.
AB  - Cells of the intestinal mucosa live in a harsh environment and therefore rely
      heavily on the highly regulated process of cell death, apoptosis, to maintain
      tissue integrity. Imbalance in the intracellular events that modulate apoptosis
      may contribute to the pathogenesis of inflammatory bowel disease.

PMID- 10961593
TI  - NF-kappaB signaling proteins as therapeutic targets for inflammatory bowel
      diseases.

PMID- 10961594
TI  - Clinical evaluation and management of acute severe colitis.
AB  - This review concentrates on the clinical evaluation, imaging, therapy, and
      prognostic factors in acute severe colitis of idiopathic as well as infectious
      origin. Older concepts as well as more recent are critically scrutinized.

PMID- 10961595
TI  - Palliative care in inflammatory bowel disease: an evidence-based approach.
AB  - The management of the patient with inflammatory bowel disease (IBD) is
      challenging for both the physician and the patient. IBD imposes both a physical
      and emotional burden on patients' lives. Palliative care is important for IBD
      patients because it focuses on improving quality of life. While palliative care
      does not change the natural history of the disease, it provides relief from pain
      and other distressing symptoms. This article focuses on various aspects of care
      for IBD patients including pain control, management of oral and skin ulcerations,
      stomal problems in IBD patients, control of nausea and vomiting, management of
      chronic diarrhea and pruritus ani, evaluation of anemia, treatment of steroid
      related bone disease, and treatment of psychological problems associated with
      IBD. Each of these areas is reviewed using an evidence-based approach. Evidence
      in category A refers to evidence from clinical trials that are randomized and
      well controlled. Category B Evidence refers to evidence from cohort or case
      controlled studies. Category C is evidence from case reports or flawed clinical
      trials. Evidence from category D is limited to the clinical experience of the
      authors. Evidence labelled as category E refers to situations where there is
      insufficient evidence available to form an opinion. Algorithms for management of
      pain and nausea in IBD patients are presented.

PMID- 10961597
TI  - Surgical management is the preferred option for major internal fistulae.

PMID- 10961596
TI  - Medical management of major internal fistulae in Crohn's disease.

PMID- 10961598
TI  - Immunosuppressors for inflammatory bowel disease: how long is long enough?
AB  - Immunosuppressors used in inflammatory bowel disease (IBD) are useful in
      refractory, chronic, active, steroid-dependent, or steroid-resistant IBD, but do
      not provide a permanent cure for IBD, their effect being only temporary. Only
      azathioprine and methotrexate are currently prescribed in the long term for IBD.
      The question of how long immunosuppressors should be given once remission has
      been induced and steroids discontinued has not yet been answered.

PMID- 10961599
TI  - Linkage of inflammatory bowel disease to human chromosome 6p.

PMID- 10961601
TI  - Dysplastic polyps in chronic colitis: is colectomy needed?

PMID- 10961600
TI  - Anti-IL12 imposes the death sentence on Th1 cells in TNBS colitis--is there a
      light at the end of the tunnel for Crohn's disease?

PMID- 10961602
TI  - Cells of the monocyte-macrophage lineage and pathogenesis of HIV-1 infection.
AB  - It is thought that monocyte-macrophages and probably dendritic cells play a
      central role in HIV-1 primary infection, as well as in its evolution, given that
      they are among the first cells infected and later function as important
      reservoirs for the virus. These cells may participate in the selection of certain
      viral strains instead of others. Levels of CCR5 coreceptor expression on the
      surface of monocytes and macrophages determine their susceptibility to infection
      by HIV-1 strains using this coreceptor and may explain, in part, the differences
      in the infectivity of these cells through the maturation process. However,
      selection for certain strains is not only determined by the level of coreceptor
      expression, but by the biochemical properties of the different coreceptors and
      their relationship with other surface molecules and the chemokine and cytokine
      networks, which also influence the selective viral infection and replication in
      these cells. Any current or newly designed therapies need to be evaluated,
      including careful analysis of the levels of HIV-1 infection of the cells of the
      monocyte-macrophage lineage, because these cells are both significant viral
      reservoirs and a center of virus production at all stages of the disease.

PMID- 10961603
TI  - Interactions among combinations of two and three protease inhibitors against drug
      susceptible and drug-resistant HIV-1 isolates.
AB  - Protease inhibitors used in combination with reverse transcriptase inhibitors
      have demonstrated potent anti-HIV-1 activity in vitro as well as in vivo. We
      evaluated interactions among five protease inhibitors: indinavir (IDV), ritonavir
      (RTV), saquinavir (SQV), amprenavir (APV), and nelfinavir (NFV), when used in
      combinations of two and three drugs in vitro against several HIV-1 isolates,
      including those susceptible and resistant to various nucleoside and nonnucleoside
      reverse transcriptase inhibitors. Interactions ranged from synergy to slight
      antagonism depending on the viral isolates and the experimental conditions
      employed. Further clinical evaluation of protease inhibitor combinations is
      warranted.

PMID- 10961604
TI  - Impact of early HIV-1 RNA and T-lymphocyte dynamics during primary HIV-1
      infection on the subsequent course of HIV-1 RNA levels and CD4+ T-lymphocyte
      counts in the first year of HIV-1 infection. Sydney Primary HIV Infection Study
      Group.
AB  - Plasma HIV-1 RNA and CD4+ T-cell counts after HIV-1 seroconversion are important
      independent markers that predict the clinical course of HIV-1 infection. The
      prognostic significance of these parameters during primary HIV-1 infection,
      however, remains largely unknown. In a cohort of 53 male study subjects (age, 33
      +/- 7 years), who consecutively presented with primary HIV-1 infection, we
      analyzed the relationship between early plasma HIV-1 RNA, CD4+ and CD8+ T-cell
      counts, beta2-microglobulin, and p24-antigen levels determined in the first 3
      months and subsequent plasma HIV-1 RNA levels and CD4+ T-cell counts 6 to 12
      months after onset of primary symptoms. Peak, nadir, and median HIV-1 RNA levels
      in the first 30 days were already significantly associated with HIV-1 RNA levels
      at 6 to 12 months (p = .02, p < .0001, and p = .01, respectively). Similarly,
      early nadir and median CD4+ T-lymphocyte counts in the first 30 days showed a
      significant relationship with CD4+ T-cell counts at 6 to 12 months (p = .009 and
      p = .0008, respectively). Study subjects with an early decline of CD4+ counts to
      <500 cells/microl had an eightfold higher risk that CD4+ counts were <500
      cells/microl at 1 year. Of all evaluated virologic parameters, only nadir HIV-1
      RNA at 76 days predicted CD4+ counts at 6 to 12 months (p = .006). Early HIV-1
      RNA levels and CD4+ counts are already associated with the time course of those
      parameters 6 to 12 months after onset of symptoms. Nadir viral load was the
      strongest predictor of HIV-1 RNA levels as well as of CD4+ counts at 6 to 12
      months. An early decline of CD4+ T lymphocytes may be a useful clinical
      prognostic marker for rapid disease progression.

PMID- 10961605
TI  - Telomere loss in peripheral blood mononuclear cells may be moderately accelerated
      during highly active antiretroviral therapy (HAART).
AB  - It has been speculated that infection with HIV-1 may lead to a significant
      increase in turnover, and subsequent exhaustion, of immune repopulation. Given
      that telomeric DNA is lost on mitotic replication, telomere lengths can be used
      as an indirect gauge of this rate. We have analyzed the mean telomere restriction
      fragment lengths in peripheral blood mononuclear cells (PBMC) from 31 patients
      with established, though mainly untreated, HIV infection and found them to be no
      different than those among healthy controls. Our results are in line with several
      findings in CD4+ cell fractions but contradict a previous report suggesting that
      telomere shortening contributes to immune failure. Interestingly, after
      approximately 2 years of subsequent aggressive antiretroviral treatment we found
      a telomere reduction corresponding to a loss of about 250 base pairs per year;
      this is roughly tenfold above that predicted from healthy individuals. This could
      partly result from nucleoside analogue inhibition of the natural telomere
      replacement enzyme, telomerase-a reverse transcriptase inducible in certain
      hematopoietic cells. However, this may also indicate accelerated cell replacement
      on initiation of optimal therapeutic regimes or result from changes in the
      composition of the PBMC pool. These results suggest careful monitoring of
      telomere lengths during long-term HAART.

PMID- 10961606
TI  - Efavirenz, nelfinavir, and stavudine rescue combination therapy in HIV-1-positive
      patients heavily pretreated with nucleoside analogues and protease inhibitors.
AB  - Tolerability, activity, and pharmacokinetic parameters of a combination therapy
      with efavirenz (EFV), nelfinavir (NFV), and stavudine (d4T) were evaluated in
      this study. Forty-seven HIV-1-infected study subjects, naive to NFV and
      nonnucleoside reverse transcriptase inhibitors (NNRTIs), who had experienced
      virologic failure while being treated with combination antiretroviral therapies
      including protease inhibitors (PIs), were enrolled. At baseline, HIV-1 viral load
      in plasma was 4.8 log10, CD4+ count was 204 cells/microl (both mean values);
      patients had received a mean of 3.1 different treatments (range, 2-5 treatments).
      Study medications were generally well tolerated; 7 of 47 patients (14.8%) were
      dropped from the study because of related drug toxicity. At week 24, mean plasma
      viral load (pVL) was reduced by 1.9 log10, with mean CD4+ count increased to 324
      cells/microl (+/-59% from baseline); pVL was below the limit of detection (500
      copies/ml) in 46.1% of patients. An extended follow-up study was performed at 12
      months. Results showed a reduction of 1.7 log10 in pVL from basal values that was
      consistent with values observed at months 3 and 6. A history of previous use of
      PIs represented a negative prognostic marker. Sequencing analysis, performed in a
      subset of patients, showed the presence of multiple point mutations associated
      with PI resistance. Pharmacokinetic analysis demonstrated a marked
      interindividual variability in NFV plasma concentrations, producing in 4 of 18
      patients (22%) trough concentrations lower than minimum effective concentration.
      In pretreated patients, further studies are needed to characterize the
      pharmacokinetic factors that affect response to therapy and the association of
      these results with the 95% inhibitory concentration (IC95) determined by
      phenotyping.

PMID- 10961607
TI  - Intravenous drug use, relationship with providers, and stage of HIV disease
      influence the prescription rates of protease inhibitors.
AB  - OBJECTIVE: To assess rates of prescriptions of protease inhibitors (PI) and
      determinants of not being prescribed PIs in a cohort of HIV-infected people
      eligible (according to published guidelines) for highly active antiretroviral
      therapy (HAART). DESIGN: Cross-sectional survey. METHODS: A total of 684 patients
      with CD4+ counts <500 cells/microl were enrolled from seven Italian HIV treatment
      centers from October 1997 to April 1998. A questionnaire on health-related
      quality of life (MOS-HIV) and patient ratings of the quality of care was
      administered. Sociodemographic variables, HIV disease-related factors, and
      prescribed antiretroviral therapy were also recorded. RESULTS: 61% of those
      enrolled were prescribed PI (median, 7.5 months). In addition, 75% of patients
      had previously received antiretroviral therapy. Fewer than 1% were prescribed
      nonnucleoside reverse transcriptase inhibitors (NNRTIs). Using multivariable
      logistic regression considering those with CD4+ counts <500 cells/microl,
      patients reporting the least information received (odds ratio [OR], 1.78; 95%
      confidence interval [CI], 1.23-2.58), injecting drug users (IDUs; OR, 1.73; 95%
      CI, 1.18-2.54), people with CD4+ counts >200 cells/microl (OR, 1.76; 95% CI, 1.19
      2.61), and patients with early stage disease (OR, 2.24; 95% CI, 1.73-2.90) were
      less likely to have be prescribed PIs. CONCLUSIONS: Of patients eligible for
      HAART, only 61% were prescribed PIs. People who wanted more information, IDUs,
      and patients in earlier disease stages are significantly less likely to be
      prescribed PIs. Access to HAART remains a critical issue in the management of HIV
      disease.

PMID- 10961608
TI  - Immunologic responses of HIV-1-infected study subjects to immunization with a
      mixture of peptide protein derivative-V3 loop peptide conjugates.
AB  - V3 loop peptide sequences from several HIV-1 strains were covalently linked to
      purified protein derivative (PPD) of Mycobacterium tuberculosis. A mixture of PPD
      conjugates of V3 loop peptides from six different strains of HIV-1 induced a
      stronger antibody response than a single V3 peptide-conjugate administered to
      guinea pigs and humans. Sera from animals immunized with a PPD-six peptide-PPD
      conjugate neutralized multiple primary-isolate strains of HIV-1. Potent immune
      responses were noted only when animals were primed with bacillus Calmette-Guerin
      (BCG), PPD was covalently bound to the peptides, and PPD was used as the carrier
      protein. Based on these animal studies, an immunogen consisting of PPD-conjugated
      V3 loop peptides from five HIV-1 strains was tested in 7 HIV-1 seropositive PPD
      skin test positive study subjects. Vaccinees exhibited over time a uniform
      increase in neutralizing antibodies for both laboratory adapted and primary
      isolates of HIV-1, including strains from multiple clades. In 3 patients with
      baseline viral loads between 8000 and 12,000 RNA copies/ml, the viral load
      declined in 2 patients to <400 copies/ml and in 1 patient to 1200 copies/ml
      without concurrent administration of highly active antiretroviral therapy
      (HAART).

PMID- 10961609
TI  - Incorporation of 3'-azido-3'-deoxythymidine (AZT) into fetal DNA and fetal tissue
      distribution of drug after infusion of pregnant late-term rhesus macaques with a
      human-equivalent AZT dose.
AB  - In the United States, the nucleoside analogue drug 3'-azido-3'deoxythymidine
      (AZT; also called zidovudine or ZDV) is given to most pregnant women who produce
      a positive test result for HIV-1. To investigate transplacental distribution and
      genotoxicity of AZT, near-term pregnant rhesus (Macaca mulatta) monkeys and their
      fetuses were studied. Four pregnant monkeys were continuously infused with 8 mg
      AZT/kg body weight for the 4 hours just prior to hysterotomy at term. This short
      term AZT exposure resulted in AZT incorporation into DNA of fetal liver, lung,
      heart, skeletal muscle, brain, testis, and placenta, which varied between 29 and
      1944 molecules of AZT/10(6) nucleotides. In contrast, values for AZT and combined
      metabolites, determined by radioactivity, varied between 0.94 and 5.20 microg AZT
      equivalents/g tissue. A fifth animal, (H076), was infused with 17.3 mg AZT/kg
      body weight for approximately 3 hours, followed by 1 hour without drug before
      hysterotomy. Similar to the 4 other monkeys, variable levels of AZT (16-147
      molecules of AZT/10(6) nucleotides) were incorporated into organ DNA of H076,
      whereas organ tissues contained less-variable levels of AZT and metabolites (0.86
      2.05 microg AZT equivalents/g tissue). For H076, at hysterotomy 1 hour after
      discontinuation of drug, values for AZT and the 3'-azido-3'-deoxythymidine-beta-D
      glucuronide (AZTG) in fetal blood and amniotic fluid were twofold and threefold
      higher than those in maternal blood. Most AZT pharmacokinetic parameters in the
      fifth monkey were similar to those previously reported for the first 4 monkeys
      and those observed in a similar study of pregnant women. These data show that a
      short-term AZT infusion in pregnant rhesus monkeys, which have similar AZT
      pharmacokinetics to those present in a pregnant human, results in incorporation
      of drug into the DNA of placenta and most fetal organs. Data imply that the human
      fetus may also be subject to incorporation of AZT into DNA even after short-term
      AZT infusion to the mother just before delivery.

PMID- 10961611
TI  - High-risk sexual behavior in Los Angeles: who receives testing for HIV?
AB  - No recent population-based data on HIV testing in people with high-risk sexual
      behavior are available. We sought predictors of testing using data from the 1997
      Los Angeles County Health Survey, a random-digit telephone survey of 8004 county
      households. An estimated 2.3 million (35.5%) adults were tested for HIV in the
      past 2 years and approximately 370,000 (5.6%) engaged in high-risk sexual
      behavior (defined as having > or =2 partners in the past 12 months and not always
      using condoms). Among high-risk persons, an estimated 46% of heterosexual men,
      56% of heterosexual women, and 72% of men who had sex with men (MSM) were tested
      for HIV. In a multivariable model of high-risk people, both heterosexual men
      (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.16-0.61) and women (OR,
      0.41; 95% CI, 0.19-0.87) had significantly lower proportions of testing than MSM.
      Although African Americans and Hispanics had significantly higher testing
      proportions than whites overall among all county residents, those reporting high
      risk sexual behavior did not test at higher proportions. We conclude that the
      proportion of adults with high-risk sexual behavior tested for HIV is higher than
      almost a decade ago. However, testing among this group remains suboptimal. Future
      public health campaigns should intensify efforts to encourage HIV testing among
      this population.

PMID- 10961610
TI  - Detection of early HIV infection and estimation of incidence using a
      sensitive/less-sensitive enzyme immunoassay testing strategy at anonymous
      counseling and testing sites in San Francisco.
AB  - Timely estimates of HIV incidence are needed to monitor the epidemic and target
      primary prevention but have been difficult to obtain. We applied a sensitive/
      less-sensitive (S/LS) enzyme immunoassay (EIA) testing strategy to stored HIV
      positive sera (N = 452) to identify early infections, estimate incidence, and
      characterize correlates of recent seroconversion among persons seeking anonymous
      HIV testing in San Francisco from 1996 to 1998 (N = 21,292). Sera positive on a
      sensitive EIA but negative on a less-sensitive EIA were classified as early HIV
      infections; sera positive on both EIA were classified as long standing. Seventy
      nine sera were from people with early HIV infection. Estimated HIV incidence was
      1.1% per year (95% confidence interval [CI], 0.68%-1.6%) overall and 1.9% per
      year (95% CI, 1.2%-3.0%) among men who have sex with men (MSM). Early HIV
      infection among MSM was associated with injection drug use, unprotected receptive
      anal sex, and multiple sex partners in the previous year. No temporal trend in
      HIV incidence was noted over the study period. The S/LS strategy provides a
      practical public health tool to identify early HIV infection and estimate HIV
      incidence in a variety of study designs and settings.

PMID- 10961613
TI  - Characteristics of hospitalizations of HIV-infected patients: an analysis of data
      from the 1994 healthcare cost and utilization project.
AB  - Hospitals are significant resources for care of HIV/AIDS patients. Previous
      studies that have attempted to identify and track the characteristics of these
      patients and their hospitalizations have been limited in their ability to produce
      national estimates of patient use of such resources. This study, using data from
      the Healthcare Cost and Utilization Project (HCUP-3) attempted to characterize
      and estimate the cost of hospital usage by HIV/AIDS patients. We estimate that in
      1994 approximately 188,506 admissions of HIV/AIDS patients occurred with an
      average charge of $19,244 U.S. per admission, for an estimated total cost of
      $3.63 billion. Compared with non-HIV-infected patients, HIV/AIDS patients tended
      to be male (75.83% versus 41.49%), a member of a minority group (53.51% versus
      20.77%), hospitalized in a private, nonprofit, urban teaching hospital with a
      longer average length of stay (10.27 versus 5.52 days), and to have a higher in
      hospital mortality (11.45% versus 2.58%). Approximately half of the hospital
      charges (47%) for these admissions were absorbed by Medicaid, and 25% by private
      insurance. The remainder of the charges were borne by the patients themselves.
      The results presented here for 1994 predate the widespread use of protease
      inhibitor/ highly active antiretroviral therapy (HAART), thus making this study
      an important benchmark for the delineation of the effects of HAART and any other
      future developments in HIV therapy on the characteristics of HIV/AIDS patient
      resource use on a national level. This study further demonstrates that HCUP is a
      powerful tool for the estimation and costing of hospital resource use.

PMID- 10961612
TI  - Adherence to antiretroviral medications in an inner-city population.
AB  - Adherence to antiretroviral medications is essential for optimal treatment of HIV
      infection. We investigated nonadherence to antiretroviral medications in an inner
      city population by using a confidential interview and a self-administered
      anonymous questionnaire. We estimated adherence on the day before and the month
      before the interview and asked reasons for nonadherence. Of 173 people who were
      taking antiretroviral medications, all participated in the confidential interview
      and 101 also completed the anonymous questionnaire. Results of the confidential
      interview and the anonymous questionnaire revealed rates of 6% and 28%,
      respectively, for nonadherence to any drug on the preceding day and of 11% and
      39%, respectively, in the preceding month. The most common reasons for
      nonadherence in both methods were forgetfulness, inaccessibility of medications,
      and perceived or actual toxicity. On 12% of the anonymous questionnaires one
      reason for nonadherence was perceived or actual lack of drug efficacy: this
      reason was not given in any of the confidential interviews. Responses about the
      extent of nonadherence and the reasons for it may differ depending on the method
      of ascertainment. Interventions to improve adherence should focus on making
      medication dosages easier to remember, ensuring a continued supply of
      medications, and circumventing toxicities.

PMID- 10961614
TI  - Immunologic and clinical stages in HIV-1-infected Ugandan adults are comparable
      and provide no evidence of rapid progression but poor survival with advanced
      disease.
AB  - Clear understanding of the natural history of HIV-1 disease is critical for
      planning and developing appropriate therapeutic strategies for HIV-1-infected
      populations in the developing world. Present knowledge about Africa is based on
      very limited data that largely use clinical staging as the prognostic marker;
      this approach has not been prospectively validated. Our objectives were to
      compare clinical staging and CD4+ T-cell counts as prognostic tools and to
      describe survival and cause of death in seroprevalent HIV-1-infected Ugandan
      adults by means of a prospective cohort study. Consecutive HIV-1-infected adults
      registering with a community HIV/AIDS clinic in Entebbe, Uganda were enrolled
      between October 1994 to January 1995 and observed during follow-up until the end
      of December 1997. Baseline CD4+ T-cell count distribution showed clear and
      appropriate associations with clinical stage in the 201 participants. Both
      provided equivalent prognostic information: median survival with CD4+ T-cell
      count <200 cells/microl was 9 months (95% confidence interval [CI], 7-15 months)
      compared with 19 and 7 months (95% CI, 10-28 and 0-8 months, respectively) in
      clinical stages 3 and 4, respectively; survival at 3 years with CD4+ T-cell count
      > or =200 cells/microl was 68% and for clinical stage 1 and 2, 80% and 60%,
      respectively. Clinical stage 3 and 4 were 76% sensitive and 65% specific for
      predicting a CD4+ T-cell count <200 cells/microl, positive predictive value of
      56%, negative predictive value 78%. In all, 82 participants died (41%; mortality
      rate 216 of 1000 person-years) and was strongly associated with low CD4+ T-cell
      counts. In conclusion, clinical staging is valid and comparable with staging by
      CD4 T-cell counts for epidemiologic measurements. Mortality with early disease in
      Entebbe appears equivalent to that found in the developed world but there is poor
      survival with advanced disease.

PMID- 10961615
TI  - Fenfluramine blocks low-Mg2+-induced epileptiform activity in rat entorhinal
      cortex.
AB  - PURPOSE: The entorhinal cortex (EC) represents the main input structure to the
      hippocampus and seems to be critically involved in temporal lobe epilepsy.
      Considering that the EC receives a strong serotonergic projection from the raphe
      nuclei and expresses a high density of serotonin (5-HT) receptors, the effect of
      the 5-HT-releasing drug fenfluramine (FFA) on epileptiform activity generated in
      the EC was investigated in an in vitro model of epilepsy. METHODS: The
      experiments were performed on 43 horizontal slices containing the EC, the
      subiculum, and the hippocampal formation obtained from 230-250 g adult Wistar
      rats. Using extracellular recording techniques, we investigated the effect of
      bath-applied FFA (200 micromol/L to 1 mmol/L) on epileptiform activity induced by
      omitting MgSO4 from the artificial cerebrospinal fluid. RESULTS: We demonstrate
      that FFA reversibly blocks epileptiform activity in the EC. Surprisingly, in the
      presence of the 5-HT uptake blocker paroxetine, the FFA-induced effect was
      diminished. Coapplication of the 5-HT1A receptor antagonist WAY100635 prevented
      the FFA-induced anticonvulsive effect, suggesting that (a) the FFA-induced
      suppression of epileptiform activity is mediated by the release of 5-HT from
      synaptic terminals within the EC rather than by an unspecific effect of FFA and
      (b) released 5-HT most likely blocks the activity by activation of 5-HT1A
      receptors. CONCLUSION: FFA, which is primarily used because of its anorectic
      activity, might get an additional therapeutic value in the treatment of temporal
      lobe epilepsy with parahippocampal involvement.

PMID- 10961616
TI  - Simultaneous kindling of the bilateral hippocampi: an advanced model for epilepsy
      research.
AB  - PURPOSE: To examine whether simultaneous kindling of bilateral hippocampi
      [bilateral kindling (BK)] could accelerate the achievement of seizures by the
      breakdown of kindling antagonism or decelerate the achievement of seizures by its
      enhancement. METHODS: The hippocampi of 17 adult rabbits were simultaneously
      kindled bilaterally according to Goddard's method. RESULTS: All animals developed
      stage 5 convulsions after a mean of 28 stimulations. Six animals showed
      spontaneous seizure discharges. Afterdischarge duration increased abruptly during
      the early period of kindling, but thereafter it gradually progressed.
      Chronological analyses of interictal discharges (IIDs) demonstrated that simple
      as well as complex types of IIDs increased their frequencies during BK.
      CONCLUSIONS: Compared with unilaterally kindled animals, the BK procedure
      significantly increased the percentage of animals that successfully kindled (100%
      vs. 59%; p < 0.01), whereas it significantly decelerated the kindling progression
      (28 days vs. 19 days; p < 0.02). We conclude that the BK procedure represents
      potentiation of both excitatory and inhibitory mechanisms. Although the reason
      why such an antagonistic relationship between them breaks down is still unknown,
      the BK provides an advanced animal model to study the pathogenic mechanisms of
      kindling and to screen anticonvulsants.

PMID- 10961617
TI  - The ketogenic diet inhibits epileptogenesis in EL mice: a genetic model for
      idiopathic epilepsy.
AB  - PURPOSE: The ketogenic diet (KD) is a high-fat, low-carbohydrate and -protein
      diet that has been used to treat refractory seizures in children for more than 75
      years. However, little is known about how the KD inhibits seizures or its effects
      on epileptogenesis. Several animal models of epilepsy have responded favorably to
      KD treatment, but the KD has not been studied in animals with a genetic
      predisposition to seizures. Here we studied the antiepileptogenic effect of the
      KD in EL mice, an animal model for human idiopathic epilepsy. METHODS: Young male
      EL mice (postnatal day 30) were randomly separated into two groups fed ad libitum
      with either the KD (treated, n = 21) or Agway chow (control, n = 19). The mice
      were weighed and tested for seizures once per week for a total of 10 weeks. The
      effects of the KD on plasma levels of ketone bodies and glucose were analyzed at
      several time points throughout the study. Associative learning was compared
      between treated and control animals using a water maze. RESULTS: KD treatment
      delayed seizure onset in young male EL mice by 1 month; however, seizure
      protection was transient, inasmuch as the treated and control mice experienced a
      similar number and intensity of seizures after 6 weeks on the diet. Plasma
      glucose levels and associative learning were similar in the treated and control
      groups, but the plasma beta-hydroxybutyrate levels were significantly higher in
      mice on the KD. The level of ketosis, however, was not predictive of seizure
      protection in EL mice. CONCLUSION: The KD delayed seizure onset in EL mice,
      suggesting a transient protection against epileptogenesis. The KD did not
      influence plasma glucose levels or associative learning. Therefore, the EL mouse
      may serve as a good model to study the antiepileptogenic mechanisms of the KD.

PMID- 10961618
TI  - Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic
      seizures.
AB  - PURPOSE: NER is a mutant rat strain that exhibits spontaneous tonic-clonic
      convulsions accompanied by epileptic discharges on ictal EEG and serves as a
      model for generalized tonic-clonic seizures in humans. Our previous experiments
      have suggested that a major autosomal recessive gene and several minor genes
      regulate the inheritance of tonic-clonic seizures in NER. The purpose of this
      study was to confirm the mode of inheritance and to locate the causative genes
      for epilepsy in NER on the rat genetic map. METHODS: We developed F1 hybrid (F1)
      and reciprocal back-cross progenies of NER with a seizure-resistant strain, F344,
      and evaluated their seizure susceptibility under tossing-stimulated and
      nonstimulated conditions. Backcross animals were genotyped using simple sequence
      length polymorphism markers for polymerase chain reactions. Linkage between
      seizure susceptibility and marker loci was analyzed by chi2 statistic tests and
      by the computer programs MAPMAKER/EXP and MAPMAKER/QTL. RESULTS: Under tossing
      stimulating conditions, tonic-clonic seizures were provoked in 90% of NER and 66%
      of (F1 x NER) backcross animals, but no seizures occurred in the F344, F1, or (F1
      x F344) backcross animals. Routine monitoring of nonstimulated animals revealed
      spontaneous tonic-clonic convulsions in 100% of NER and 64.2% of (F1 x NER)
      backcross animals, but no seizures in F344 or F1. Gender effect on seizure
      susceptibility was negligible in (F1 x NER) backcross in both conditions.
      Preliminary genome-wide scanning and subsequent precise location of the causative
      genes revealed seizure susceptibility loci, designated Ner1 and Ner2, on rat
      chromosomes 1 and 3, respectively. CONCLUSIONS: Ner1 is a locus that controls the
      inheritance of spontaneous tonic-clonic seizures in an autosomal recessive mode,
      whereas Ner2 affects the occurrence of tossing-induced seizures. Orthologous
      genes in the vicinity of these loci may be related to epileptogenesis in other
      species, including humans.

PMID- 10961619
TI  - The role of brain computed tomography in evaluating children with new onset of
      seizures in the emergency department.
AB  - BACKGROUND: The purpose of neuroimaging of a patient with new onset of seizures
      is to demonstrate cause and explore the prognosis. It was recently recommended
      that emergency brain computed tomography (CT) be performed only in adult seizure
      patients with an increased likelihood of life-threatening lesions, i.e., those
      with new focal deficits, persistent altered mental status, fever, recent trauma,
      persistent headaches, history of cancer, history of anticoagulation, or suspicion
      of acquired immunodeficiency syndrome. The objective of this study was to
      determine the diagnostic utility of emergency brain CT in children who present to
      the emergency department with new onset of seizures. METHODS: A 1-year
      retrospective chart review of all children who presented to the emergency
      department of the Schneider Children's Hospital with a new onset of seizures and
      who underwent CT of the brain, excluding children with simple febrile seizures.
      RESULTS: Sixty-six patients, 34 boys and 32 girls with a mean age of 4.9 years,
      qualified for inclusion in the study. Fifty-two patients (78.8%) had normal CT
      results and 14 patients (21.2%) had abnormal CT results. Seizure cause was
      considered cryptogenic in 33 patients, of whom 2 (6%) had abnormal CT results;
      neither patient required intervention. Seizure cause was considered symptomatic
      in 20 patients, of whom 12 (60%) had abnormal CT results (p < 0.0001). In two
      patients with abnormal CT scans (both acute symptomatic), the imaging findings
      were of immediate therapeutic significance and were predictable from the clinical
      history and the physical examination. None of the 13 patients with complex
      febrile seizure cause had an abnormal CT scan. Patients with partial convulsive
      seizures were more likely to have abnormal CT scans than patients with
      generalized convulsive seizures, but the difference was not statistically
      significant. CONCLUSIONS: The routine practice in many pediatric emergency
      departments of obtaining brain CT scans for all patients with new onset of
      nonfebrile seizures is unjustified. History and physical examination are
      sufficient to identify those patients for whom such studies are likely to be
      appropriate. Emergent CT is not indicated for patients with no known seizure risk
      factors, normal neurological examinations, no acute symptomatic cause other than
      fever, and reliable neurological follow-up. For these patients, referral to a
      pediatric neurologist for further workup, including electroencephalography and
      the more diagnostically valuable magnetic resonance imaging, would be more
      appropriate.

PMID- 10961620
TI  - The clinical usefulness of ictal SPECT in temporal lobe epilepsy: the
      lateralization of seizure focus and correlation with EEG.
AB  - PURPOSE: To analyze the relationship between ictal electroencephalography (EEG)
      and ictal single-photon emission computed tomography (SPECT) and to evaluate the
      diagnostic usefulness of ictal SPECT as an independent presurgical evaluation
      technique. METHODS: Sixty-eight patients with temporal lobe epilepsy who
      underwent temporal lobectomy with good surgical outcome were included in this
      study. Ictal SPECT was performed during video-EEG monitoring. The ictal EEG was
      analyzed in 5-second intervals from the initiation of the ictal rhythm.
      Lateralized EEG dominance was determined by the amplitude, frequency, or regional
      patterns of ictal rhythm for each 5-second interval. The total ictal EEG was
      divided into three periods: preinjection (maximum, 30 seconds), the initial part
      of the postinjection period (30 seconds), and the latter part of the
      postinjection period (30 to 60 seconds). The results of ictal SPECT were compared
      with the lateralized EEG dominance of each period and at seizure onset. RESULTS:
      Fifty-four of 68 ictal EEGs correctly lateralized seizure focus ipsilateral to
      the side of surgery. Ictal SPECT correctly lateralized the epileptogenic temporal
      lobe in 61 of 68 patients (mean injection time, 29.8 seconds from onset).
      Multivariate analysis indicated that only the EEG dominance of the preejection
      period correlated significantly with the concordant hyperperfusion of ictal
      SPECT. Correct lateralization of ictal SPECT occurred in 10 of 14 patients with
      nonlateralized ictal EEG. CONCLUSIONS: Preinjection neuronal activity seems to be
      important for the accurate interpretation of the hyperperfused patterns of ictal
      SPECT. Ictal SPECT is an independent and confirmatory presurgical evaluation
      technique.

PMID- 10961621
TI  - Predictive value of MRI-identified mesial temporal sclerosis for surgical outcome
      in temporal lobe epilepsy: an intent-to-treat analysis.
AB  - PURPOSE: Magnetic resonance imaging (MRI) accurately identifies mesial temporal
      sclerosis (MTS), but prediction of successful surgical outcome ranges from 62% to
      96% in published studies. Prior investigations only used patients who had
      received anterior temporal lobectomy (ATL), potentially overestimating the
      predictive value of MRI-identified MTS (MRI-MTS). METHODS: The authors performed
      an intent-to-treat analysis of 90 consecutive patients assessed for possible ATL,
      including 13 who did not undergo ATL because of inconclusive intracranial ictal
      EEG. Four (31%) of these 13 patients had unilateral mesial temporal abnormalities
      on their MRIs. RESULTS: The positive predictive value of MRI-MTS for seizure
      cessation decreased from 0.69 to 0.63 after adjustment for these additional false
      positive results. Four previous studies had revealed a positive predictive value
      of 0.75 (0.72 after similar adjustment). CONCLUSIONS: The authors conclude that
      the predictive value of MRI-MTS for outcome from ATL may be overestimated by
      small retrospective studies of highly selected postoperative patients.

PMID- 10961622
TI  - Autosomal dominant partial epilepsy with auditory features: description of a new
      family.
AB  - PURPOSE: To report the clinical and genetic study of a new family with autosomal
      dominant partial epilepsy with auditory features (ADPEAF). METHODS: All the
      living affected members underwent a full clinical, neurophysiological, and
      magnetic resonance imaging (MRI) study. Genetic analysis was performed by typing
      their DNA with seven microsatellite markers previously found to cosegregate with
      ADPEAF on chromosome 10q24. RESULTS: The three living affected members had a
      childhood onset of rare and drug-responsive tonic-clonic seizures constantly
      preceded by a humming sensation. Routine and sleep electroencephalograms revealed
      rare and inconstant focal abnormalities over both temporal regions. MRI detected
      atrophy with increased T2 signal in the subcortical lateral portion of the right
      temporal lobe in one case. Analysis of 10q24 polymorphic alleles showed the same
      haplotype in all three affected members but different alleles in unaffected
      individuals. CONCLUSIONS: ADPEAF is a distinct condition with homogeneous
      clinical features. Genetic findings are consistent with linkage of ADPEAF to
      chromosome 10q24.

PMID- 10961623
TI  - Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit
      NR2A/B in human focal cortical dysplasia.
AB  - PURPOSE: Human cortical dysplasia (CD) is a frequent cause of medically
      intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity
      in these lesions have been attributed to changes in various glutamate receptor
      subtypes. Increased N-methyl-D-aspartate (NMDA) receptor (NR) 2A/B coassembled
      with NR1 subunits has been shown in focal epileptic CD. The purpose of this study
      is to correlate in situ CD epileptogenicity and the expression of various
      glutamate receptor subtypes. METHODS: The histopathological, morphological, and
      immunocytochemical findings in cortical tissue resected from five patients with
      medically intractable epilepsy and CD were correlated with
      electroencephalographic data recorded from subdural grids. The NMDA antibodies
      identified subunits NR1 (splicing variants 1a, 1b, 2a, and 2b) and NR2A/B.
      RESULTS: Epileptogenic specimens displayed the following common features: (a)
      widespread histological abnormalities of horizontal and columnar dyslamination,
      neurons with inverted polarity, and more extensive dendritic changes; (b)
      significantly higher NR2A/B immunoreactivity in both the dysplastic somata and
      all their dendritic processes; and (c) no statistically significant change in NR1
      subunit expression but a more pronounced staining of the apical dendrites in
      highly epileptogenic cortex. These abnormalities were either absent or minimal in
      resected specimens that did not show evidence of severe in vivo epileptogenicity.
      CONCLUSION: These studies provide direct evidence for a major contribution of the
      NR2A/B subunit in CD-induced epileptogenicity.

PMID- 10961624
TI  - Topiramate in refractory epilepsy: a prospective observational study.
AB  - PURPOSE: This prospective observational study explored the efficacy and
      tolerability of topiramate (TPM) in patients with refractory epilepsy attending a
      single outpatient clinic. METHODS: One hundred seventy patients (82 men, 88
      women, aged 18-75 years) with refractory localization-related (n = 134) or
      idiopathic generalized epilepsy (n = 36) were started on adjunctive TPM using a
      standard titration schedule. TPM was introduced after a 3-month prospective
      baseline, and doses were adjusted according to clinical response. End points were
      seizure freedom for 6 months, > or =50% seizure reduction for 6 months compared
      with baseline at the highest tolerated TPM dose (responder), or discontinuation
      of TPM because of side effects, lack of efficacy, or both. RESULTS: Thirty-nine
      (23%) patients were seizure-free, and 80 (47%) more patients had a useful
      therapeutic response. Thirteen seizure-free patients and 16 responders took 100
      mg of TPM daily or less. TPM was discontinued in 51 (30%) patients. The most
      common side effects resulting in withdrawal were fatigue, weight loss,
      irritability, paresthesia, depression, and headache. Concomitant antiepileptic
      drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM
      monotherapy, eight of whom remained seizure-free. Final TPM doses and
      concentrations varied widely among the three outcome groups. CONCLUSIONS: TPM was
      efficacious as add-on and monotherapy in patients with refractory partial and
      generalized seizures in everyday clinical use. A good response was obtained in
      many patients with TPM doses substantially lower than those studied in regulatory
      clinical trials. The wide variation in dose-response and dose-toxicity
      relationships may reflect different neurobiologies causing refractory epilepsy
      and differential efficacy of AED combinations.

PMID- 10961625
TI  - Status epilepticus-induced neuronal loss in humans without systemic complications
      or epilepsy.
AB  - PURPOSE: To determine the regional distribution of neuronal damage caused
      strictly by status epilepticus (SE) without systemic complications, underlying
      brain pathology, or a history of preexisting epilepsy. METHODS: The medical
      records and electroencephalograms (EEGs) of three deceased patients who developed
      SE in the hospital were reviewed. Their brains were formalin-fixed, and 17 brain
      regions were selected, embedded in paraffin, and sectioned. Alternate sections
      were stained with either hematoxylin and eosin and cresyl violet to determine the
      extent of neuronal loss and gliosis or glial fibrillary astrocytic protein to
      confirm the extent of astrocytic proliferation. RESULTS: The three patients died
      11 to 27 days after the onset of focal motor SE; none had hypotension, hypoxemia,
      hypoglycemia, or significant hyperthermia. Two patients had no prior seizures and
      no underlying brain pathology. The third patient, who had leptomeningeal
      carcinomatosis, had one seizure 2 months before the onset of SE. The duration of
      SE was 8.8 hours to 3 days. EEGs showed unilateral temporal lobe sharp-wave
      discharges in one patient and independent temporal lobe sharp-wave discharges
      bilaterally in the other two patients. In addition to widespread neuronal loss
      and reactive gliosis in the hippocampus, amygdala, dorsomedial thalamic nucleus,
      and Purkinje cell layer of the cerebellum, we report for the first time
      periamygdaloid (piriform) and entorhinal cortical damage occurring acutely after
      SE in humans. CONCLUSIONS: In the absence of systemic complications or
      preexisting epilepsy, SE produces neuronal loss in a distribution similar to that
      from domoic acid-induced SE in humans and from kainic acid- and pilocarpine
      induced SE in rats.

PMID- 10961626
TI  - Intracarotid amobarbital procedure and prediction of postoperative memory in
      patients with left temporal lobe epilepsy and hippocampal sclerosis.
AB  - PURPOSE: Although temporal lobe epilepsy (TLE) patients with dominant hemisphere
      hippocampal sclerosis generally have good cognitive outcome after anterior
      temporal lobectomy (ATL), a minority of patients experience at least mild post
      ATL decline on one or more standardized measures of episodic and semantic memory.
      The goal of this investigation was to determine whether memory outcome in this
      group could be predicted from preoperative intracarotid amobarbital procedure
      (IAP) recognition memory scores. METHODS: Data from 22 left TLE patients were
      studied retrospectively. All were left hemisphere language dominant and had IAP
      scores for each hemisphere, a significant degree of pathology-confirmed left
      hippocampal sclerosis (HS+), and no positive MRI findings other than atrophy.
      Cognitive outcome status was represented by the number of pre- to post-ATL
      declines across three tests, as defined by 90th percentile Reliable Change Index
      (RCI) criteria. RESULTS: Only 14% of the sample exhibited decline on more than
      one memory test. Low right IAP (left hemisphere injection) scores and relatively
      high preoperative cognitive ability and age at surgery predicted a greater risk
      of post-ATL memory decline. CONCLUSIONS: A minority of left TLE HS+ patients
      experience at least a mild degree of RCI-defined decline in episodic or semantic
      memory after ATL. The right hemisphere IAP memory score, which reflects the
      functional reserve of the contralateral hemisphere, can help predict the risk of
      postoperative memory decline for TLE patients in whom HS+ is likely based on the
      presence of hippocampal atrophy on MRI or early age of seizure onset.

PMID- 10961627
TI  - Social aspects of epilepsy in the adult in seven European countries. The RESt-1
      Group.
AB  - PURPOSE: The social implications of epilepsy are ill-defined, and there are no
      comparative findings from different countries. A multicenter cohort study has
      recently been completed on the risk of morbidity and accidents. The main social
      issues in the study population (patients with epilepsy and control subjects) are
      investigated and correlated to the clinical features of the disease. METHODS:
      Seven hundred six adult patients with idiopathic or remote symptomatic epilepsy
      and 662 matched controls without epilepsy were enrolled by secondary and tertiary
      centers in seven European countries (Italy, Germany, Spain, the Netherlands,
      England, Portugal, and Russia). At entry, patients and controls were interviewed,
      and data were collected on social variables (education, current occupation,
      marital status, driving, involvement in sports, and insurance). The main clinical
      features of epilepsy (seizure types, frequency and timing, disease duration, and
      syndrome) were also recorded. RESULTS: The sample included 690 men and 678 women
      aged 18 to 86 years. The level of education (mostly basic or high school) was
      slightly higher among patients with epilepsy. More patients than controls were
      single (56% versus 50%) or unemployed (18% versus 13%). Fewer patients than
      controls held a driver's license (44% versus 67%) or practiced sports (30% versus
      41%). The distribution of each social variable varied significantly across
      countries, but with few exceptions, the differences between patients and controls
      were fairly similar. Based on multivariate analysis, for patients with epilepsy
      the odds ratio for driving was 0.27, and the corresponding odds ratios for sports
      involvement, better education, better occupation, and insurance were 0.59, 1.30,
      0.60, and 1.49. Among patients with epilepsy, social variables were correlated to
      seizure remission and selected clinical features. CONCLUSIONS: Comparative
      findings from different European countries support the concept that epilepsy has
      a considerable impact on driving and-to a lesser extent-on education, occupation,
      leisure activities, and insurance. The social implications of epilepsy in this
      sample are partly related to its severity and clinical features.

PMID- 10961628
TI  - Seizure recurrence after a first unprovoked seizure in childhood: a prospective
      study.
AB  - PURPOSE: To study the risk of recurrence after a first unprovoked seizure in
      childhood. METHODS: All consecutive patients aged less than 14 years with one or
      more unprovoked seizures who were attended between January 1, 1987, and June 1,
      1996, were included in a prospective study. Clinical features of patients
      attended after a first seizure and those attended after two or more seizures were
      compared. Recurrence risk in both groups was estimated by Kaplan-Meier curves.
      Univariate and multivariate analyses of the potential predictors of recurrence
      risk were performed for the group of patients attended after a first seizure
      using the Cox proportional hazards model. RESULTS: Included in the study were 217
      children. Kaplan-Meier estimate of recurrence risk was 64% at 5 years, when only
      patients being attended after a first epileptic seizure were included, compared
      with 74% when all patients were included. Significant differences in several
      clinical features were found between patients attended after a first seizure and
      those attended after two or more seizures. Univariate and multivariate analyses
      showed that in the overall cohort of patients attended after a first seizure, a
      symptomatic etiology increased the risk of recurrence, whereas a patient age of 3
      to 10 years decreased this risk. In particular, the recurrence risk was 96% at 2
      years for symptomatic seizures, compared with 46% for idiopathic/cryptogenic
      seizures. In the group of patients with idiopathic/cryptogenic seizures, an
      abnormal electroencephalogram and the occurrence of seizures during sleep
      increased the recurrence risk, whereas a patient aged 3 to 10 years reduced it.
      In the group of patients with symptomatic etiology, univariate analysis revealed
      that there was a lower recurrence risk for patients aged 3 to 10 years. This last
      finding was not maintained, however, in multivariate analysis. CONCLUSIONS: The
      recurrence risk depends on the inclusion criteria for enrolling patients. Several
      factors enable us to predict the recurrence risk after a first unprovoked
      seizure; the most important of these factors is the etiology of the seizures.

PMID- 10961629
TI  - Newly diagnosed epilepsy: can nurse specialists help? A randomized controlled
      trial. Epilepsy Care Evaluation Group.
AB  - PURPOSE: To describe a group of people with newly diagnosed epilepsy and to test
      the effect of an epilepsy nurse specialist on patients' knowledge of epilepsy,
      satisfaction with the advice provided, and psychological well-being. METHODS:
      Neurologists in the United Kingdom (U.K.) recruited adults with newly diagnosed
      epilepsy. Patients were randomized to receive the offer of two appointments with
      an epilepsy nurse specialist or usual medical care. The main outcome measures
      were a questionnaire assessing patients' knowledge of epilepsy, the Hospital
      Anxiety and Depression Scale, and patients' reported satisfaction with the advice
      and explanations provided on key epilepsy-related topics. RESULTS: Ninety people
      with new epilepsy completed the trial. At baseline, fewer than half the patients
      reported having been given enough advice on epilepsy, and there were important
      differences in patients' knowledge of epilepsy. Lack of a U.K. school-leaving
      examination pass (General Certificate School Examination) was associated with
      lower knowledge of epilepsy (p = 0.03). At follow-up, the patients randomized to
      see the nurse specialist were significantly more likely to report that enough
      advice had been provided on most epilepsy-related topics compared with the
      control group. There were no significant differences in knowledge of epilepsy
      scores. However, there were significant differences in the group who, at
      baseline, had knowledge scores in the lowest quartile; those randomized to the
      nurse had higher knowledge scores (42.7 vs. 37.2; p < 0.01). Compared with
      doctors, the nurse was highly rated for providing clear explanations.
      CONCLUSIONS: Patients who have less general education have less knowledge of
      epilepsy. The introduction of a nurse specialist in epilepsy is associated with a
      significant increase in patient reports that enough advice has been provided.
      Nurse intervention appears to help those with the least knowledge of epilepsy
      improve their knowledge scores.

PMID- 10961630
TI  - A comparison of two methods for estimating the health care costs of epilepsy.
AB  - PURPOSE: Previous studies have estimated medical care costs of epilepsy by
      applying unit costs to estimated utilization or by summing costs for (a)
      ambulatory care and hospitalizations coded as epilepsy and (b) procedures and
      drugs specifically associated with the diagnosis or treatment of epilepsy. These
      methods may underestimate the cost of medical care for epilepsy. Two methods for
      estimating the medical care costs of epilepsy ("epilepsy-attributable cost
      method" and "case-control cost method") were compared. METHODS: The study
      population was 655 individuals with an epilepsy diagnosis enrolled in a managed
      care plan in the southwestern United States. The epilepsy-attributable costs were
      determined by summing costs for inpatient and outpatient encounters coded as
      epilepsy, procedures for the diagnosis or treatment of epilepsy, and drugs used
      to treat epilepsy. The case-control method determined costs by calculating the
      difference in total costs between cases and 1,965 age- and gender-matched
      controls. RESULTS: The case-control epilepsy costs were $2,923 per case compared
      with epilepsy-attributable costs of $1,335 per case. The case-control method
      found statistically significant differences in costs between cases and controls
      for inpatient care, prescription drugs, and 8 of 11 categories of outpatient
      care. The largest contributors to the discrepancy between estimates were
      inpatient care, emergency department care, laboratory tests, and "other
      specialist" care. CONCLUSIONS: Epilepsy-attributable costs accounted for only 46%
      of the total difference in costs between epilepsy cases and controls. Persons
      with epilepsy use more medical services than controls, but a substantial portion
      of this care is not coded to epilepsy.

PMID- 10961631
TI  - Prevalence, knowledge, attitude, and practice of epilepsy in Kerala, South India.
AB  - PURPOSE: To ascertain the prevalence and pattern of epilepsy and to characterize
      and quantify knowledge, attitude, and practice (KAP) toward epilepsy among the
      people of the state of Kerala, which is distinguished from the rest of India by a
      high level of literacy and health awareness of its population. METHODS: We
      conducted a door-to-door survey covering the entire population of 238,102 people
      residing in 43,681 households in a semiurban area of central Kerala. The
      screening questionnaire administered by medical social workers had a sensitivity
      of 100% for identifying persons with epilepsy. Neurologists examined all the
      individuals suspected of having epilepsy. We evaluated KAP toward epilepsy among
      1,118 subjects (439 males and 679 females; mean age, 33.3 years; age range, 15-85
      years) from households without epilepsy in the study area. RESULTS: Through a
      three-phased survey, we ascertained 1,175 cases (616 males and 559 females) with
      active epilepsy, providing a crude point prevalence ratio of 4.9 cases per 1,000
      people and an age-adjusted prevalence ratio of 4.7 cases per 1,000 population.
      The highest age-specific prevalence rate of 6.5 per 1,000 occurred in the 10- to
      19-year-old age group. Sex-specific prevalence rates did not significantly
      differ. The proportion of generalized and localization-related epilepsies was
      58.8% and 30.6%, respectively. Ninety-nine percent of the KAP respondents had
      read or heard about epilepsy. Thirty-one percent and 27% thought epilepsy was a
      hereditary disorder and a form of insanity, respectively. About 40% of the
      respondents felt that individuals with epilepsy could not be properly educated or
      employed. Eleven percent would object to their children having contact with
      epileptic children. CONCLUSIONS: The prevalence and pattern of epilepsy in
      central Kerala, South India, do not differ from that of developed countries.
      Although the awareness of epilepsy among the people of Kerala was comparable to
      that of developed countries, the attitudes were much more negative. The need for
      educating the people of Kerala on epilepsy and for incorporating an adequate
      knowledge of epilepsy in the school curricula cannot be overemphasized.

PMID- 10961632
TI  - Familial aphasic episodes: another variant of partial epilepsy with simple
      inheritance?
AB  - We report on a family having partial epilepsy with simple inheritance. The
      affected members commonly have aphasic episodes with secondary generalization;
      onset occurred either in adolescence or adulthood. Patients' response to
      medication has varied greatly. No neurological defects or decline in intelligence
      were found. The case represents another variety of rare familial partial epilepsy
      with neocortical epilepsy features.

PMID- 10961633
TI  - Autonomic seizures versus syncope in 18q- deletion syndrome: a case report.
AB  - PURPOSE: The 18q- deletion syndrome (18qDS) is frequently associated with cardiac
      anomalies. Patients with this syndrome may also have epilepsy, which presents
      certain diagnostic difficulties. This case report aims to illustrate these
      diagnostic problems, document the usefulness of heart rate-based seizure
      detection algorithms in this setting, and define the epilepsy syndrome associated
      with 18qDS. METHODS: Closed-circuit video electroencephalogram (EEG) monitoring
      using a heart rate-based seizure detection software was used to identify the
      event in question and to establish the diagnosis of epilepsy. Chromosomal
      analysis and magnetic resonance imaging (MRI) were used to further define the
      epilepsy syndrome. RESULTS: We report on a patient with an atrial septal defect,
      enlargement of the right heart, and incomplete right bundle branch block, who
      developed episodes of tachycardia, loss of consciousness, and pallor, for which
      he was amnesic. Chromosomal analysis demonstrated karyotype 46,XY,del(18)(q21.3).
      ish del(18)(wcp18+,D18Z1+) with a loss of the gene for myelin basic protein. MRI
      revealed multifocal dysmyelination. Video-EEG monitoring using an
      electrocardiogram (ECG)-triggered seizure detection software proved to be
      indispensable in detecting an autonomic seizure and establishing the correct
      diagnosis; the procedure also allowed for the definition of the epilepsy
      syndrome. The patient was treated with carbamazepine and remained seizure-free.
      CONCLUSIONS: Video-EEG monitoring using a heart rate-based seizure detection
      software can be helpful in diagnostically differentiating autonomic seizures from
      syncope. Dysmyelination due to loss of the myelin basic protein gene on 18q and
      cortical dysgenesis may be of pathogenic relevance.

PMID- 10961634
TI  - Community leader education to increase epilepsy attendance at clinics in Epworth,
      Zimbabwe.
AB  - OBJECTIVE: To determine whether educating community leaders about epilepsy would
      lead to an increase in epilepsy cases being diagnosed and treated at primary
      health centers. METHODS: This was a single-arm cohort study performed in Epworth,
      a periurban township outside Harare, Zimbabwe. The subjects were Epworth
      community leaders (Local Board members, teachers, nurses, police officers,
      traditional healers, prophets). Educational workshops were given on epilepsy, its
      cause, and its management, and the number of new epilepsy cases on local primary
      health clinic registers 6 months after the workshops was measured. RESULTS: Six
      new cases were recorded, all among patients previously diagnosed with epilepsy.
      This was a significant increase (p = 0.02) compared with the null hypothesis.
      CONCLUSION: Although there was a significant increase in new cases, these did not
      represent newly diagnosed patients. Significant prejudice within the community
      may still prevent identified patients with epilepsy from seeking treatment.
      Alternative methods must be sought to increase the awareness of epilepsy within
      low-income communities and to reach "hidden" people with epilepsy.

PMID- 10961635
TI  - Effects of vagus nerve stimulation on progressive myoclonus epilepsy of
      Unverricht-Lundborg type.
AB  - PURPOSE: A 34-year-old woman with progressive myoclonus epilepsy of Unverricht
      Lundborg type was considered for vagus nerve stimulation (VNS) therapy. METHODS:
      After demonstration of intractability to multiple antiepileptic regimens and
      progressive deterioration in cerebellar function, the patient was implanted with
      a vagus nerve stimulator and followed for 1 year. Neurological status, seizure
      frequency, and parameter changes were analyzed. RESULTS: VNS therapy resulted in
      reduction of seizures (more than 90%) and a significant improvement in cerebellar
      function demonstrated on neurological examination. The patient reported improved
      quality of life based in part on her ability to perform activities of daily
      living. CONCLUSIONS: VNS therapy may be considered a treatment option for
      progressive myoclonus epilepsy. The effects of VNS on seizure control and
      cerebellar dysfunction may provide clues to the underlying mechanism(s) of
      action.

PMID- 10961636
TI  - Benign focal epilepsies of childhood: genetically determined pathophysiology.
      Report of an international workshop.

PMID- 10961637
TI  - Clinical spectrum of benign focal epilepsies of childhood.

PMID- 10961638
TI  - The electroencephalographic features of benign centrotemporal (rolandic) epilepsy
      of childhood.

PMID- 10961639
TI  - Drug treatment of benign focal epilepsies of childhood.

PMID- 10961641
TI  - The genetics of rolandic epilepsy.

PMID- 10961640
TI  - Autosomal dominant nocturnal frontal lobe epilepsy.

PMID- 10961642
TI  - Properties underlying the influence of nicotinic receptors on neuronal
      excitability and epilepsy.
AB  - The great diversity of neuronal nAChRs equips them for many roles. The broad,
      diffuse projections of the cholinergic system and their influence on multiple
      neurotransmitter systems enable nAChRs to have a wide modulatory influence on
      excitability on multiple time scales. Both excitatory and inhibitory synapses are
      directly modulated by nAChR activity. Although fast nicotinic transmission is not
      a major excitatory drive, it may alter the excitability of many synapses at one
      time. Depending on the neural area and stage of development, nAChRs of multiple
      subtypes will have varying degrees of importance in regulating neuronal
      excitability.

PMID- 10961643
TI  - Novel K+ channel genes in benign familial neonatal convulsions.

PMID- 10961645
TI  - Molecular identity of the M-channel.

PMID- 10961646
TI  - Potassium channels and dendritic function in hippocampal pyramidal neurons.

PMID- 10961644
TI  - Pathophysiology of KCNQ channels: neonatal epilepsy and progressive deafness.

PMID- 10961647
TI  - Calcium channel defects in models of inherited generalized epilepsy.

PMID- 10961648
TI  - Circuit mechanisms of spike-wave discharge: are there similar underpinnings for
      centrotemporal spikes?

PMID- 10961649
TI  - Developmental neuroplasticity and epilepsy.

PMID- 10961650
TI  - Transient actions of neurotransmitters during neocortical development.

PMID- 10961651
TI  - Modulation of intrinsic circuits in developing neocortex.

PMID- 10961652
TI  - Benign focal epilepsies of childhood: genetically determined pathophysiology-
      epilepsy that comes and goes.
AB  - Developmental processes; the types of neuron expressing particular gene products;
      the sites of these receptors/channels, transporters, etc., on neurons and in
      circuits; and compensatory processes such as activation of other genes,
      sprouting, pruning, and receptor plasticity will determine the nature of the
      epileptic phenotype induced by a particular genetic alteration, and the ultimate
      functional outcome.

PMID- 10961654
TI  - Alteration in dopamine metabolism in the thermoregulatory center of exercising
      rats.
AB  - To examine the role of monoamines and amino acids in thermoregulation, we
      measured their concentrations in the preoptic area and anterior hypothalamus
      (PO/AH) in exercising rats, using an in vivo microdialysis technique. Body
      temperature (Tb) was monitored using a telemetry system. Tb increase by about 1.0
      degrees C in the first 15 min of treadmill exercise (10 m/min; for 60 min), and
      was maintained thereafter at a steady high level possibly due to activation of
      the heat loss system. The levels of dopamine metabolites (3,4
      dihydroxyphenylacetic acid and homovanillic acid) in the PO/AH significantly
      increased during exercise. However, exercise did not induce an increase in the
      level of either serotonergic substances (5-hydroxytryptamine and 5
      hydroxyindoleacetic acid) or amino acids (aspartate and glutamate). Our data
      indicate that dopamine breakdown processes in the PO/AH are activated during
      exercise. Dopamine in the PO/AH may be involved in the heat loss mechanisms for
      thermoregulation when Tb rises during exercise.

PMID- 10961653
TI  - Lack of SOD1 gene mutations and activity alterations in two Italian families with
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive fatal disorder, which
      results from the degeneration of motor neurons in the brain and spinal cord.
      Approximately 20% of the inherited autosomal dominant cases are due to mutations
      within the gene coding for Cu/Zn superoxide dismutase 1 (SOD1), a cytosolic
      homodimeric enzyme that catalyzes the dismutation of toxic superoxide anion. We
      investigated the presence of SOD1 gene mutations and activity alterations in two
      unrelated families of ALS patients from Elba, an island of central Italy. No
      mutation in SOD1 exon 1 to 5 and no activity alteration were observed in all
      members of the two analyzed ALS families (FALS). These data show an apparent
      heterogeneous distribution of ALS patients with SOD1 gene mutations among
      different populations and suggest that another genetic locus could be involved in
      the disease.

PMID- 10961655
TI  - Increase in level of tumor necrosis factor-alpha in 6-hydroxydopamine-lesioned
      striatum in rats is suppressed by immunosuppressant FK506.
AB  - We compared in rats with 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism the
      content of tumor necrosis factor (TNF)-alpha in the nigrostriatal dopaminergic
      region of the control side with that of the 6-OHDA-injected experimental side,
      and explored the effects of 6-OHDA injection combined with the immunosuppressant
      FK506 treatment (0.5 or 4 mg/kg per day for 2 weeks). The ratios of the
      concentration of TNF-alpha in the striatum and substantia nigra on the 6-OHDA
      injection side to that on the control side in the 6-OHDA hemiparkinsonism rats
      were significantly higher than those in the control rats without 6-OHDA
      treatment, whereas those in the rats treated with 6-OHDA and FK506 were not
      significantly different from those in the control rats. Thus FK506 attenuated
      increased TNF-alpha level in the nigrostriatal dopaminergic region injured by 6
      OHDA treatment.

PMID- 10961656
TI  - Time-sharing contributions of A- and D-type K+ channels to the integration of
      high-frequency sequential excitatory post synaptic potentials at a model dendrite
      in rats.
AB  - A- and D-type K+ channels (KA and KD channels) have unique physiological
      properties that play important roles in the integration of excitatory post
      synaptic potentials (EPSPs) in neuronal dendrites. These functions were analyzed
      using a computer program, NEURON, to simulate high-frequency sequential synaptic
      inputs, that can induce long-term potentiation (LTP). We paid close attention to
      the stability of the reduction of sequential EPSPs. When either KA or KD channels
      were included in models, the EPSP reduction ratios were less stable than
      containing both KA and KD channels. When both KA and KD channels were present in
      the model, the variance of EPSP reduction ratios was significantly smaller in
      comparison with that in the presence of either KA or KD channels alone. We thus
      concluded that the co-existence of KA and KD channels is necessary to produce
      stable EPSPs during the high-frequency synaptic stimulation necessary for
      induction of LTP.

PMID- 10961657
TI  - Induction of heme oxygenase-1 in the brains of scrapie-infected mice.
AB  - Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the rate-limiting
      step in the degradation of heme to biliverdin, carbon monoxide and iron, and its
      expression can be used as a marker for oxidative stress. Oxidative stress has
      been reported to be associated with neurodegenerative diseases including
      Alzheimer's disease. It is possible that oxidative stress is also involved in the
      disease process seen in scrapie, the archetype transmissible spongiform
      encephalopathy. In this study, we report that HO-1 is significantly increased in
      the scrapie-infected group compared to an age-matched control group.
      Immunohistochemistry showed a pronounced increase of immunostaining of this
      protein in the infected group compared to the minimal amount of staining in the
      control group. These results support that oxidative stress is closely associated
      with the pathogenesis of scrapie and that it might contribute to
      neurodegeneration in this disease.

PMID- 10961658
TI  - ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) is
      transcriptionally induced in beta-amyloid treated rat astrocytes.
AB  - Beta-amyloid (Abeta) deposition is considered to be of the most crucial events in
      the onset of Alzheimer's disease (AD). To identify factors involved in the
      exacerbation of AD, we investigated transcriptionally Abeta-induced genes using a
      cDNA subtraction technique in rat astrocytes as previously reported. One
      subtracted gene that showed the Abeta-induced expression was rat ADAMTS-4 (a
      disintegrin and metalloproteinase with thrombospondin motifs). In this report, we
      present the deduced sequence for the mature form of rat ADAMTS-4 and demonstrate
      the induction of its mRNA by treatment of cells with Abeta. Our results suggest a
      degradation of the extracellular matrix occurring in the brain of AD patients and
      a possibly significant role of this enzyme in the progression of AD.

PMID- 10961659
TI  - Effects of physostigmine and calcium on acetylcholine efflux from the hippocampus
      of freely moving rats as determined by in vivo microdialysis and a
      radioimmunoassay.
AB  - The effects varying the concentration of Ca2+ in perfused artificial
      cerebrospinal fluid ([Ca2+]csf) on basal acetylcholine (ACh) efflux from the
      hippocampus of freely moving rats, in the presence and absence of the
      cholinesterase (ChE) inhibitor physostigmine, were investigated using in vivo
      microdialysis and a highly specific radioimmunoassay for ACh. In the absence of
      physostigmine, basal ACh efflux was 3.4+/-0.7 pg/30 min (mean +/- SEM) at
      [Ca2+]csf = 1.26 mM. Stepwise increases in [Ca2+]csf elicited a gradual increase
      in ACh efflux that was significant at [Ca2+]csf = 5.04 mM. Inhibition of ChE by
      addition of 10 microM physostigmine to the perfusate increased the efflux of ACh
      to 103.2+/-21.1 pg/30 min ([Ca2+]csf = 1.26 mM), and the efflux was augmented
      still further by increasing [Ca2+]csf, a change that became significant at
      [Ca2+]csf = 3.78. These results illustrate the sensitivity of basal ACh efflux
      from the hippocampus to changes in the extracellular Ca2+ concentration, and
      suggest that a more accurate picture of hippocampal cholinergic activity is
      obtained by microdialysis using normal artificial cerebrospinal fluid, under
      physiological conditions, rather than in the presence of a ChE inhibitor.

PMID- 10961660
TI  - Decreased cortical levels of astrocytic glutamate transport protein GLT-1 in a
      rat model of posttraumatic epilepsy.
AB  - The extracellular homeostasis of glutamate in the brain is maintained by the
      efficient uptake into astroglial cells. The high extracellular glutamate levels
      seen during seizures are therefore probably a result of both an increased
      synaptic release and a deranged glutamate uptake. In this study we used immuno
      blotting technique to measure the cortical levels of the astrocytic glutamate
      transport protein (GLT-1) and of the glutamate and aspartate transporting protein
      (GLAST) in an epilepsy model induced by ferrous chloride injection in the cortex
      of rats. The levels of GLT-1 were lower in epileptic rats than in controls, day 1
      and 5 after induction, but not at 3 months. Glial fibrillary protein (GFAP)
      levels increased with time in the epileptic model, whereas GLAST and beta-tubulin
      III remained unchanged compared to controls. The results suggest that the
      transient decrease of GLT-1 could play a role in epileptogenesis, while recurrent
      seizure activity may be maintained by other mechanisms.

PMID- 10961662
TI  - Altered representation of peripersonal space in the elderly human subject: a
      sensorimotor approach.
AB  - The representation of the peripersonal space in humans and its modification with
      aging were studied by analyzing three-dimensional arm movements in healthy young
      and elderly adults. Participants drew ellipses in three reference planes
      (sagittal, frontal and horizontal), and errors in the orientation of ellipses
      with regard to the planes were measured. All subjects showed large disparities in
      the errors in different planes, errors were maximal in the horizontal plane.
      These findings imply that different planes are centrally represented with
      different errors and suggest that the mental representation of peripersonal space
      is anisotropic. Moreover, the elderly made larger errors than young subjects,
      regardless of the reference plane. Thus, the space representation is altered with
      aging. Compared with young adults, the elderly underestimate volume in space, a
      phenomenon that can be called the compression of space representation.

PMID- 10961661
TI  - Protective effect of gamma-glutamylethylamide (theanine) on ischemic delayed
      neuronal death in gerbils.
AB  - We examined the protective effect of gamma-glutamylethylamide (theanine) on
      ischemic delayed neuronal death in field CA1 of the gerbil hippocampus. One
      microliter of theanine from each three concentrations (50, 125 and 500 microM)
      was administered through the lateral ventricle 30 min before ischemia. Transient
      forebrain ischemia was induced by bilateral occlusion of the common carotid
      arteries for 3 min under careful control of brain temperature at approximately 37
      degrees C. Seven days after ischemia, the number of intact CA1 neurons in the
      hippocampus was assessed. Ischemia-induced neuronal death in hippocampal CA1
      region was significantly prevented in a dose-dependent manner in the theanine
      pretreated groups. These findings indicate that theanine might be useful
      clinically for preventing ischemic neuronal damage.

PMID- 10961663
TI  - Immunocytochemical localization of putative gamma-aminobutyric acid receptor
      subunits in the head ganglia of Periplaneta americana using an anti-RDL C
      terminal antibody.
AB  - A polyclonal antibody raised against a 17 amino acid polypeptide (the predicted C
      terminal sequence of the cloned Drosophila melanogaster gamma-aminobutyric acid
      (GABA) receptor subunit, RDL) was used to investigate the distribution of GABA
      receptor subunit(s) of this type in the nervous system of the cockroach
      Periplaneta americana. Intense staining was detected in the calyces of the
      mushroom bodies, glomeruli of the antennal lobes, lower central body, the corpora
      cardiaca and several cell layers of the medulla and the lobula regions of the
      optic lobe. The most intense immunocytochemical staining was in the
      suboesophageal ganglion. Control sections pre-incubated with the primary antibody
      and conjugated peptide were not stained. Thus, it appears that a GABA receptor
      subunit of the RDL type is located in cockroach brain regions involved in the
      processing of visual, olfactory and mechanosensory inputs to the nervous system.
      Since the corpora cardiaca reacted to this antiserum, this type of GABA receptor
      may also be involved in the regulation of neurosecretory activity.

PMID- 10961664
TI  - Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of Alzheimer's
      disease, although the underlying mechanisms are unknown. Glutamate excitotoxicity
      has been implicated in Alzheimer's disease, Parkinson's disease, and others. We
      examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary
      rat embryonic neurons from mesencephalon, the area primarily affected in
      Parkinson's disease. We evaluated whether these drugs protect dopaminergic
      neurons against excitotoxicity. All three NSAIDs significantly attenuated the
      decrease in dopamine uptake caused by glutamate, indicating preservation of
      neuronal integrity. One hundred micro-moles ibuprofen protected both dopaminergic
      neurons and neurons overall against glutamate toxicity. In addition, ibuprofen
      alone increased the relative number of dopaminergic neurons by 47%. Thus, NSAIDs
      protected neurons against glutamate excitotoxicity in vitro, and deserve further
      consideration as neuroprotective agents in Parkinson's disease.

PMID- 10961665
TI  - Glatiramer acetate (copolymer-1)-specific, human T cell lines: cytokine profile
      and suppression of T cell lines reactive against myelin basic protein.
AB  - Glatiramer acetate (GA), represents an established treatment of
      relapsing/remitting multiple sclerosis (MS). The mechanisms responsible for the
      effect of GA are not fully understood. We generated GA-, myelin basic protein
      (MBP)- and purified protein derivative (PPD)-specific T cell lines from three MS
      patients and one healthy donor. The GA-specific lines were CD3+, CD4+, CD8- and
      produced tumor-necrosis-factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma),
      interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) after
      stimulation with GA in the presence of irradiated peripheral blood mononuclear
      cells. MBP-specific T cell lines showed an identical phenotype and secreted TNF
      alpha, IFN-gamma, IL-4, IL-10, but not IL-6. Co-culture experiments demonstrated,
      that GA-specific T cell lines have the capability to suppress the proliferation
      of MBP-specific T cell lines.

PMID- 10961667
TI  - Alzheimer's risk associated with human apolipoprotein E, alpha-2 macroglobulin
      and lipoprotein receptor related protein polymorphisms: absence of genetic
      interactions, and modulation by gender.
AB  - Apolipoprotein E (apoE), the lipoprotein receptor related protein (LRP) and alpha
      2 macroglobulin (alpha2M) have been proposed as a functional complex involved in
      amyloid clearance, a crucial event for Alzheimer's disease development. In this
      work, we present an epidemiological approach aimed to study the interactions
      among these genes, age and gender. This approach did not reveal significant
      associations between the genes; however, the present study indicated that the
      risk associated with APOE promoter and LRP gene polymorphisms is modulated by
      gender.

PMID- 10961666
TI  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced complex I inhibition is
      reversed by disulfide reductant, dithiothreitol in mouse brain.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes dopaminergic cell loss
      in mice by inhibiting mitochondrial complex-I through its metabolite, MPP+, which
      binds to specific sites on complex-I. Since complex-I is highly vulnerable to
      oxidative stress, we have examined the nature of inhibition of complex-I by MPTP.
      Both MPTP and MPP+ inhibited complex-I activity, in vitro, in mouse brain slices,
      which was abolished by prior exposure of brain slices to glutathione. Further,
      the inhibited complex-I activity rebounded after incubation with disulfide
      reductant, dithiothreitol. Systemic administration of MPTP to mice resulted in
      inhibition of complex-I in striatum and midbrain which was also reversed by
      treatment of mitochondria with dithiothreitol. Inhibition of complex I activity
      by MPTP may be due to oxidation of thiol group(s) in complex-I, which may be
      reversed by thiol antioxidants.

PMID- 10961668
TI  - Neurotrophins and trk-receptors in adult rat spinal motoneurons: differences
      related to cell size but not to 'slow/fast' specialization.
AB  - We have studied the mRNA expression of the neurotrophins brain-derived
      neurotrophic factor (BDNF), NT-3 and NT-4 and of their receptors trkB and trkC in
      individual retrogradely labeled lumbar spinal motoneurons of the adult rat, using
      quantitative non-radioactive in situ hybridization (ISH). We measured soma size
      and the optical density of the ISH reaction. We analyzed mRNA expression patterns
      in predominantly 'slow' or 'fast' motoneurons by comparing retrogradely labelled
      cells that innervated the slow m.soleus (Sol) with those innervating the fast
      m.extensor digitorum longus (EDL). Within individual motoneuron pools, there was
      a considerable variation in the intensity of mRNA expression encoding for BDNF,
      NT-3 and NT-4, as well as for the receptors trkB and trkC. The expression of trkC
      mRNA was significantly higher in small, presumed fusimotor neurons than in the
      larger alpha-motoneurons. Surprisingly, none of the variations in the level of
      motoneuronal mRNA expression for trkB, BDNF, NT-3 and NT-4 were related to soma
      size and no differences were found between EDL and Sol motoneurons. Apparently,
      the considerable variations in neurotrophin and neurotrophin receptor mRNA
      expression represent other parameters of motoneuronal specialization than those
      related to the well-established 'fast' vs. 'slow' categories of motoneurons.

PMID- 10961669
TI  - CuZn-superoxide dismutase transgenic mice: no effect on longevity, locomotor
      activity and 3H-mazindol and 3H-spiperone binding over 19 months.
AB  - This study was designed to determine whether CuZn-superoxide dismutase (SOD) is
      neuroprotective against aging in the nigrostriatal tract. Twenty-four male mice
      transgenic for human CuZnSOD, resulting in overexpression of the cytosolic
      enzyme, were compared with 11 matched controls over 19 months. There was no
      difference in longevity, locomotor activity, or 3H-mazindol or 3H-spiperone
      binding in the nigrostriatal tract in the two groups. Thus there was no evidence
      that increased CuZnSOD was neuroprotective in this model.

PMID- 10961670
TI  - Allelic association between the D10S1423 marker and Alzheimer's disease in a
      German population.
AB  - Recently a full genome survey detected an allelic association between Alzheimer's
      disease (AD) and the D10S1423 marker on chromosome 10p12-14 (40 cM from the
      telomere). In this study we examined the D10S1423 marker in an ethnically
      homogeneous German population of 80 AD patients and two groups of controls, 168
      healthy subjects and 149 depressed patients. The 234-bp allele of the D10S1423
      marker showed a significant association with AD (P = 0.033). In conclusion, our
      results support that the D10S1423 marker is associated with an increased AD risk
      and provides further evidence for an AD susceptibility locus on chromosome 10.

PMID- 10961671
TI  - Pleasant odors attenuate the blood pressure increase during rhythmic handgrip in
      humans.
AB  - We have investigated the effects of inhaling odors of preference on physiological
      responses to physical exercise in college students. Rhythmic handgrip,
      maintaining a mercurial pressure by repetitive compression, increased blood
      pressure. In the participants exercised with inhaling odors of their choice, such
      as rose, jasmine and lavender, the increase in diastolic blood pressure during
      exercise was reduced by 24%. In contrast, the blood pressure increase during
      static handgrip, maintaining the power 30-40% of maximum, was not affected by the
      existence of favorite odors. Since the blood pressure increase during static
      handgrip is a lower brainstem reflex, the present result shows that the
      inhalation of favorite odors suppresses the muscle sympathetic vasoconstrictor
      activity and attenuates the blood pressure increase by affecting the central
      nervous system higher than the midbrain.

PMID- 10961672
TI  - Effects of apolipoprotein E phenotypes on the neuropsychological functions of
      community-dwelling elderly individuals without dementia.
AB  - Studies have demonstrated that different apolipoprotein E (APOE) phenotypes
      appear to modulate the effects of cognitive aging in Caucasian elderly
      populations. Few studies have investigated the effects of the common APOE alleles
      on the neuropsychological functioning in other ethnic elderly populations. We
      examined the different effects of APOE polymorphism on the neuropsychological
      functions of 213 community-dwelling Korean elderly individuals without dementia.
      Individuals with APOE epsilon4 allele performed poorly on memory measures,
      Recency of the Elderly Verbal Learning Test, Immediate and Delayed Reproductions
      of the Simplified Rey Figure Test (SRFT), the Primary Memory Index, and the
      Secondary Memory Index. They also performed worse on the sub-scale assessing
      executive function on the Korean-Dementia Rating Scale (K-DRS). Subjects with
      APOE epsilon2 allele performed better on visuo-spatial measures, the Construction
      sub-scale of the K-DRS, and the Copy and Immediate Reproductions of the SRFT.

PMID- 10961673
TI  - A simple model for predicting the free energy of binding between anthracycline
      antibiotics and DNA.
AB  - A theoretical model for predicting the free energy of binding between
      anthracycline antibiotics and DNA was developed using the electron density
      functional (DFT) and molecular mechanics (MM) methods. Partial DFT-ESP charges
      were used in calculating the MM binding energies for complexes formed between
      anthracycline antibiotics and oligodeoxynucleotides. These energies were then
      compared with experimental binding free energies. The good correlation between
      the experimental and theoretical energies allowed us to propose a model for
      predicting the binding free energy for derivatives of anthracycline antibiotics
      and for quickly screening new anthracycline derivatives.

PMID- 10961674
TI  - Tautomers of styrylquinoline derivatives containing a methoxy substituent:
      computation of their population in aqueous solution and their interaction with
      RSV integrase catalytic core.
AB  - 8-Hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethenyl]-7-quinoline carboxylic acid
      and 8-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethenyl]-7-quinoline carboxylic
      acid inhibit the processing and strand transfer reactions catalyzed by HIV-1
      integrase with an IC50 of 2 microM. Some of their spectral properties are briefly
      reported. Their fluorescence is so weak that it is of no use in an experimental
      determination of the binding to the protein and we resorted to computer
      simulation. Both styrylquinoline derivatives, in their monoanionic form, have
      several dozens of tautomers and each of these forms has four planar rotamers. In
      this work computer simulations have been performed to determine which tautomer is
      the most abundant in aqueous solution and which binds to the Rous sarcoma virus
      (RSV) integrase catalytic core. As the substituents on the quinoline moiety are
      the same as on salicylic acid, the energies of hydroxy benzoic acid tautomers
      were also computed both in vacuo and embedded in a continuous medium which had
      the dielectric constant of bulk water, using the recent CPCM technique. The CPCM
      method was then applied to the two integrase inhibitors to estimate the tautomer
      population in water. The binding site of the compounds on the RSV integrase
      catalytic core was determined through a docking protocol, consisting of coupling
      a grid search method with full energy minimization. The designed method is a way
      leading to identification of potent integrase inhibitors using in silico
      experiments.

PMID- 10961675
TI  - Molecular modelling, synthesis and antitumour activity of carbocyclic analogues
      of netropsin and distamycin--new carriers of alkylating elements.
AB  - A series of netropsin and distamycin analogues was synthesised and investigated
      by molecular modelling. The lowest-energy conformations of four carbocyclic
      lexitropsins, potential carriers of alkylating elements, were obtained using the
      HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures
      from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis
      of carbocyclic lexitropsins was elaborated, with the use of a nitro group or
      azobenzene as precursors for the aromatic amino group. The influence of methoxy
      group in ortho position with respect to amide groups on the activity of the new
      compounds was investigated. All of the compounds tested showed high antitumour
      activity in the standard cell line of mammalian tumour MCF-7.

PMID- 10961676
TI  - Self-organizing neural network for modeling 3D QSAR of colchicinoids.
AB  - A novel scheme for modeling 3D QSAR has been developed. A method involving
      multiple self-organizing neural network adjusted to be analyzed by the PLS
      (partial least squares) analysis was used to model 3D QSAR of the selected
      colchicinoids. The model obtained allows the identification of some structural
      determinants of the biological activity of compounds.

PMID- 10961677
TI  - The role of side chains in the interaction of new antitumor
      pyrimidoacridinetriones with DNA: molecular dynamics simulations.
AB  - Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor
      compounds. It seems reasonable to assume that, like for some other acridine
      derivatives, intercalation into DNA is a necessary, however not a sufficient
      condition for antitumor activity of these compounds. Rational design of new
      compounds of this chemotype requires knowledge about the structure of the
      intercalation complex, as well as about interactions responsible for its
      stability. Computer simulation techniques such as molecular dynamics (MD) may
      provide valuable information about these problems. The results of MD simulations
      performed for three rationally selected PATs are presented in this paper. The
      compounds differ in the number and position of side chains. Each of the compounds
      was simulated in two systems: i) in water, and ii) in the intercalation complex
      with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in
      relation to the ring system is determined by the position of its attachment.
      Orientation of the ring system inside the intercalation cavity depends on the
      number and position of side chain(s). The conformations of the side chain(s) of
      all PATs studied in the intercalation complex were found to be very similar to
      those observed in water.

PMID- 10961678
TI  - Kinetics of a nucleoside release from lactide-caprolactone and lactide-glycolide
      polymers in vitro.
AB  - We assessed the rate of release of a model nucleoside (adenosine, 5%, w/w) from
      nine different lactide-glycolide or lactide-caprolactone polymers. The polymer
      discs were eluted every second day with an artificial cerebrospinal fluid at the
      elution rate roughly approximating the brain extracellular fluid formation rate.
      Adenosine in eluate samples was assayed by HPLC. Three polymers exhibited a
      relatively constant release of adenosine for over four weeks, resulting in
      micromolar concentrations of nucleoside in the eluate. This points to the
      necessity of further development of polymers of this types as intracerebral
      nucleoside delivery systems for local treatment of brain tumors.

PMID- 10961679
TI  - The intercalation of imidazoacridinones into DNA induces conformational changes
      in their side chain.
AB  - Imidazoacridinones (IAs) are a new group of highly active antitumor compounds.
      The intercalation of the IA molecule into DNA is the preliminary step in the mode
      of action of these compounds. There are no experimental data about the structure
      of an intercalation complex formed by imidazoacridinones. Therefore the design of
      new potentially better compounds of this group should employ the molecular
      modelling techniques. The results of molecular dynamics simulations performed for
      four IA analogues are presented. Each of the compounds was studied in two
      systems: i) in water, and ii) in the intercalation complex with dodecamer duplex
      d(GCGCGCGCGCGC)2. Significant differences in the conformation of the side chain
      in the two environments were observed for all studied IAs. These changes were
      induced by electrostatic as well as van der Waals interactions between the
      intercalator and DNA. Moreover, the results showed that the geometry of the
      intercalation complex depends on: i) the chemical constitution of the side chain,
      and ii) the substituent in position 8 of the ring system.

PMID- 10961680
TI  - Biomimetic polyesters and their role in ion transport across cell membranes.
AB  - Syntheses of biomimetic low-molecular weight poly-(R)-3-hydroxybutanoate mediated
      by three types of supramolecular catalysts are presented. The utility of these
      synthetic polyesters for preparation of artificial channels in phospholipid
      bilayers capable of sodium and calcium ion transport across cell membranes, is
      discussed. Further studies on possible applications of these bio-polymers for
      manufacturing drugs of prolonged activity are under way.

PMID- 10961681
TI  - Synthesis and antimicrobial activity of new adamantane derivatives I.
AB  - A series of fourteen derivatives of adamantane was synthesised. The new compound
      4-(adamant-1-ylmethoxycarbonyl)phthalanhydride obtained from 1-adamantane
      methanol and trimellitic anhydride chloride appeared very useful for preparation
      of a number of N-substituted phthalimides. Antimicrobial activity of the newly
      obtained derivatives such as, for example, 4-(adamant-1-ylmethoxycarbonyl)-N-(5
      carboxypentamethylene)p hthalimide or 4-(adamant-1-ylmethoxycarbonyl)-N-(L
      alanyl)phthalimide was tested against Staphylococcus aureus, Bacillus sp.,
      Micrococcus flavus and Enterococcus faecium. The minimal inhibitory concentration
      (MIC) for these compounds against S. aureus were 0.022 and 0.05 microg/ml,
      respectively.

PMID- 10961682
TI  - N4-amino-acid derivatives of 6-azacytidine: structure-activity relationship.
AB  - Several N4-derivatives of 6-azacytidine were synthesized using of Vorbruggen's
      condensation method. Their antiviral activity with respect to the adenovirus
      serotypes 2 and 5 in Hep-2 cells culture was studied and primary specific
      activity was determined. Correlation between chemical structure of new 6
      azacytidine derivatives and their biological properties is discussed.

PMID- 10961683
TI  - Effect of ethanol on structural transitions of DNA and polyphosphates under Ca2+
      ions action in mixed solutions.
AB  - In the present work using the IR spectroscopy method the effect of ethanol on
      structural transitions of DNA and polyphosphates under the action of Ca2+ ions in
      mixed solutions containing ethanol (0-25 vol.%) was studied. It was shown that,
      on its interaction with Ca2+ ions, in aqueous and mixed solutions DNA becomes
      transformed into compact form. With the increase of concentration of ethanol the
      degree of Ca2+-induced DNA compactisation rises. It was found that, in mixed
      solutions containing ethanol, Ca2+-induced DNA compactisation depends not only on
      the solution's dielectric permeability but also on the solution structure. On
      stabilisation of the water structure in the presence of low ethanol
      concentrations a stabilisation of the DNA macromolecule occurs that leads to the
      increase of the Ca2+ ion concentration necessary for DNA compactisation.
      Comparison of the effects of ethanol on Ca2+-induced structural transitions in
      DNA and polyphosphates in mixed solvents permits to suppose that at alcohol
      concentrations in solution resulting in disruption of the water spatial
      structure, some peculiarities are observed in the behavior of those molecules
      whose hydrophobic interactions are essential.

PMID- 10961684
TI  - Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.
AB  - Pentamidine despite its rather high toxicity, is currently in clinical use. For
      development of new drugs of this type it is important to know the mechanism of
      their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole
      (DAPI) were found in preliminary experiments to inhibit protein synthesis in
      vitro in the cell-free rat liver system. The three compounds differed in the
      precise mode of action. The inhibitory effect of I on the activity of the
      eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the
      binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has
      been identified as the primary target of II and eEF-1 as the primary target of
      DAPI in the system studied.

PMID- 10961685
TI  - N-Methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME), a novel antifungal
      agent of low toxicity: monomer/micelle control over selective toxicity.
AB  - Rational chemical modification of amphotericin B (AMB) led to the synthesis of
      sterically hindered AMB derivatives. The selected optimal compound, N-methyl-N-D
      fructosyl amphotericin B methyl ester (MF-AME) retains the broad spectrum of
      antifungal activity of the parent antibiotic, and exhibits a two orders of
      magnitude lower toxicity in vivo and in vitro against mammalian cells.
      Comparative studies of MF-AME and AMB comprising the determination of the
      spectroscopic properties of monomeric and self-associated forms of the
      antibiotics, the investigation of the influence of self-association on toxicity
      to human red blood cells, and of the antibiotic-sterol interaction were
      performed. On the basis of the results obtained it can be assumed that the
      improvement of the selective toxicity of MF-AME could in part be a consequence of
      the diminished concentration of water soluble oligomers in aqueous medium, and
      the better ability to differentiate between cholesterol and ergosterol.

PMID- 10961686
TI  - Comparative studies on cell stimulatory, permeabilizing and toxic effects induced
      in sensitive and multidrug resistant fungal strains by amphotericin B (AMB) and N
      methyl-N-D-fructosyl amphotericin B methyl ester (MFAME).
AB  - N-Methyl-N-D-fructosyl-amphotericin B methyl ester (MFAME) is a new derivative of
      amphotericin B, which is characterised by low toxicity to mammalian cells and
      good solubility in water of its salts. The antifungal activity and effects of
      MFAME towards Candida albicans and Saccharomyces cerevisiae multidrug resistant
      MDR(+) and sensitive MDR(-) strains was compared with those of parent compound.
      The results obtained indicate that MDR(+) S. cerevisiae was sensitive to MFAME as
      well as to AMB. MFAME exhibited the same effects on fungal cells studied as
      parent antibiotic. The two antibiotics, depending on the dose applied induced
      cell stimulation, K+ efflux, and/or had a toxic effect.

PMID- 10961687
TI  - The ability of new formamidine sugar-modified derivatives of daunorubicin to
      stimulate free radical formation in three enzymatic systems: NADH dehydrogenase,
      NADPH cytochrome P450 reductase and xanthine oxidase.
AB  - Some sterically hindered N-substituted derivatives of daunorubicin are known to
      be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reductase and
      xanthine oxidase. In consequence, poor oxygen radical generation by these
      compounds is observed. In this study we examined a new family of sugar-N
      substituted derivatives of daunorubicin bearing a bulky substituent introduced on
      the nitrogen atom through the amidine spacer. These compounds were found to be
      very active in radical formation catalyzed by all three studied enzymes. Thus,
      the introduction of a heterocyclic ring, even if it is bulky but flexible, on the
      nitrogen atom of daunosamine moiety through the one-atom spacer (amidine group),
      does not induce the steric hindrance effect on the interaction of daunorubicin
      derivatives with these flavoprotein enzymes.

PMID- 10961688
TI  - c-myc oncogene gene dosage, serum CEA and CA-15.3 antigen levels, and cellular
      DNA values in relation to ex vivo chemosensitivity of primary human breast
      cancer.
AB  - A pilot study on relationships of selected molecular factors (c-myc oncogene
      average gene copy numbers (AGCN); serum CEA and CA 15.3 antigen levels; tumor
      cells' DNA values), to the ex vivo chemosensitivity of primary female human
      breast cancer in a modified adenosine triphosphate cell viability
      chemosensitivity assay (ATP-CVA), was performed. Four drug combinations were
      tested. A group of 75 cases of female primary breast cancer was assessed.
      Numerous correlations were found among molecular factors tested but none, with
      the exception of tumor grading, of these reflected ex vivo chemosensitivity of
      tumors tested. The results suggest that the parameters tested may not be
      important factors related to adjuvant chemoresponsiveness of primary human breast
      cancer to tested drug combinations.

PMID- 10961689
TI  - Relationship of c-myc and erbB oncogene family gene aberrations and other
      selected factors to ex vivo chemosensitivity of ovarian cancer in the modified
      ATP-chemosensitivity assay.
AB  - A pilot study on relationships of selected molecular factors [erbB-1, erbB-2,
      erbB-3, and c-myc oncogene average gene copy numbers (AGCN); steroid receptors
      and pS2 gene expression; tumor cells' DNA values] to the ex vivo chemosensitivity
      of ovarian cancer in a modified adenosine triphosphate cell viability
      chemosensitivity assay (ATP-CVA), was performed. Despite the relatively small
      number of patients, numerous correlations among the factors tested were found.
      Nevertheless, only c-myc gene dosage positively affected ex vivo chemosensitivity
      of tumors tested.

PMID- 10961690
TI  - Cytostatic and cytotoxic effects of (E)-2'-deoxy-2'-(fluoromethylene)-cytidine on
      a solid tumor and a leukemia cell line.
AB  - (E)-2'-deoxy-2'-(fluoromethylene)-cytidine (FMdC), a deoxycytidine analog
      displaying a very high toxicity toward a variety of solid tumor cell lines and
      xenografts, is activated intracellularly by deoxycytidine kinase (dCK). We have
      compared cytotoxicity of FMdC towards a human promyeolocytic leukemia line HL-60
      and a human colorectal carcinoma line COLO-205. Despite dCK activity being by far
      the highest in cells of lymphoid origin, the effects of FMdC were detectable at
      the lowest drug concentration only in a solid tumor cell line, and at higher
      concentrations they were qualitatively similar in the two tumor lines (increased
      cell protein content, cell cycle block and apoptosis). Apparently, low dCK
      activity in solid tumor cells sufficiently activates FMdC to yield cytotoxic
      effects, while high dCK activity in leukemia cells does not increase its
      cytotoxicity.

PMID- 10961691
TI  - ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral
      therapy.
AB  - To enhance the inhibitory potential of 1-beta-D-ribofuranosyl-1,2,4-triazole-3
      carboxamide (ribavirin) vs hepatitis C virus (HCV) NTPase/helicase, ribavirin-5'
      triphosphate (ribavirin-TP) was synthesized and investigated. Ribavirin-TP was
      prepared with the use of modified Yoshikawa-Ludwig-Mishra-Broom procedure (cf.
      Mishra & Broom, 1991, J. Chem. Soc., Chem. Commun, 1276-1277) involving
      phosphorylation of unprotected nucleoside. Kinetic analysis revealed enhanced
      inhibitory potential of ribavirin-TP (IC50=40 microM) as compared to ribavirin
      (IC50 > 500 microM). Analysis of the inhibition type by means of graphical
      methods showed a competitive type of inhibition with respect to ATP. In view of
      the relatively low specificity towards nucleoside-5'-triphosphates (NTP) of the
      viral NTPase/helicases, it could not be ruled out that the investigated enzyme
      hydrolyzed the ribavirin-TP to less potent products. Investigations on non-
      hydrolysable analogs of ribavirin-TP or ribavirin-5'-diphosphate (ribavirin-DP)
      are currently under way.

PMID- 10961692
TI  - Suppressors of translation initiation defect in hem12 locus of Saccharomyces
      cerevisiae.
AB  - A system for the positive selection of transational initiation suppressors in S.
      cerevisiae has been developed. A mutant with an ATA initiation codon in the HEM12
      gene, encoding uroporphyrinogen decarboxylase, was used to select cis- and trans
      acting suppressors. These suppressors partially restore growth on nonfermentable
      carbon sources, such as glycerol, but still allow the accumulation of porphyrins.
      All extragenic suppressors are mapped to the SUI1 locus, encoding initiation
      factor eIF1. The effect of the hem12 mutation is also partially reversed by the
      known SUI3 suppressor encoding the beta subunit of eIF2. In contrast, the sui2
      suppressor encoding the a subunit of eIF2 does not affect the hem12 phenotype.
      The intragenic suppressors are able to restore the translation of hem12 due to
      the generation of additional, in frame AUG codons upstream of the hem12-14
      mutation. Mutational analysis of the HEM12 leader sequence was also performed to
      determine the role of small open reading frames (uORFs) present upstream of the
      HEM12 ORF. Studies on the expression of integrated hem12-1/4-lacZ fusion, devoid
      of all upstream ATGs, indicate a lack of regulatory effect of uORFs on HEM12
      translation.

PMID- 10961693
TI  - Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is not
      associated with breast cancer.
AB  - The antigen content of plasminogen activator inhibitor-1 (PAI-1) in primary
      breast cancer tissue extracts may be of strong prognostic value: high levels of
      PAI-1 in tumors predict poor prognosis for patients. The gene encoding PAI-1 is
      highly polymorphic and an insertion (5G)/deletion (4G) polymorphism in the PAI-1
      gene promoter (the 4G/5G polymorphism), may have functional significance in PAI-1
      expression. In the present work the distribution of genotypes and frequency of
      alleles of the 4G/5G polymorphism in subjects with breast cancer were
      investigated. Tumor tissues were obtained from 100 postmenopausal women with node
      negative and node-positive ductal breast carcinoma with uniform tumor size. Blood
      samples from age matched healthy women served as control. The 4G/5G polymorphism
      was determined by PCR amplification using the allele specific primers. The
      distribution of the genotypes of the 4G/5G polymorphism in both control and
      patients did not differ significantly (P > 0.05) from those predicted by the
      Hardy-Weinberg distribution. There were no differences in the genotype
      distributions and allele frequencies between node-positive and node-negative
      patients. The 4G/5G polymorphism may not be linked with elevated level of PAI-1
      observed in breast cancer and therefore may not be associated with appearance
      and/or progression of breast cancer.

PMID- 10961694
TI  - Reactive oxygen species as second messengers? Induction of the expression of
      yeast catalase T gene by heat and hyperosmotic stress does not require oxygen.
AB  - It is shown that oxygen is not absolutely needed for stress-induced synthesis of
      catalase T in the yeast Saccharomyces cerevisiae. Yeast cells develop heat
      resistance after exposure to elevated temperatures in anoxia. The levels of
      catalase activity and thermotolerance are comparable to those in aerobically
      stressed cells. While these results obviously do not exclude a stress signaling
      role of reactive oxygen species in some systems, as postulated by other authors,
      they suggest that the question of the obligatory requirement for reactive oxygen
      species in other stress signaling systems should be rigorously re-investigated.

PMID- 10961695
TI  - Cloning, expression, and crystallization of Cpn60 proteins from Thermococcus
      litoralis.
AB  - Two genes of the extreme thermophilic archaeon Thermococcus litoralis homologous
      to those that code for Cpn60 chaperonins were cloned and expressed in Escherichia
      coli. Each of the Cpn60 subunits as well as the entire Cpn60 complex crystallize
      in a variety of morphological forms. The best crystals diffract to 3.6 A
      resolution at room temperature and belong to the space group 1422 with unit cell
      parameters a = b = 193.5 A, c = 204.2 A.

PMID- 10961696
TI  - Temperature-dependent regulatory mechanism of larval development of the wax moth
      (Galleria mellonella).
AB  - The mechanisms underlying larval diapause in the wax moth (Galleria mellonella)
      is one of the most throughly studied aspects. At the low temperature of 18
      degrees C, the last instar larvae did not pupate but transferred to 30 degrees C
      they initiated development and pupation in a circadian manner. Different types of
      surgical manipulations including head-ligation, nerve cord-severance,
      implantation of the brain, prothoracic glands, accompanied with ecdysteroid titre
      measurements indicated that diapausing arrest of larval development at 18 degrees
      C might be due to the nervous inhibition of their prothoracic glands.

PMID- 10961697
TI  - Glutathione conjugation in male reproductive system: studies on glutathione-S
      transferase of bull and boar epididymis.
AB  - Male reproductive organs are extremely sensitive to the negative influence of
      toxic environmental factors as well as drugs, and until now not many attempts
      have been made at studying the detoxication enzymes and the relationship between
      the activity of those enzymes and spermatozoa fertility. In the present work we
      studied cytosolic glutathione-S-transferases (GST, EC 2.5.1.18) from different
      parts (head, corpus and tail) of bull and boar epididymis. We isolated two
      molecular forms of GST from each part of epididymis, characterized their
      biochemical properties and examined the mechanism of the catalyzed reaction. On
      the basis of their substrate specificity and isoelectric point, the isoforms were
      found to belong to the near neutral GST class mi. All examined GST forms
      exhibited higher affinity towards GSH than towards 1-chloro-2,4-dinitrobenzene
      (CDNB) and bull epididymis GST forms showed biphasic Lineweaver-Burk double
      reciprocal curves in the presence of GSH as a variable substrate. Boar epididymis
      anionic GST had the -SH groups both in the GSH and the CDNB binding place,
      whereas the cationic GST form--arginine residues in the CDNB binding place. Bull
      epididymis GST forms contained neither thiol nor arginine residues essential for
      catalytic activity.

PMID- 10961698
TI  - Inhibition and activation of enzymes. The effect of a modifier on the reaction
      rate and on kinetic parameters.
AB  - A combined analysis of enzyme inhibition and activation is presented, based on a
      rapid equilibrium model assumption in which one molecule of enzyme binds one
      molecule of substrate (S) and/or one molecule of a modifier X. The modifier acts
      as activator (essential or non-essential), as inhibitor (total or partial), or
      has no effect on the reaction rate (v), depending on the values of the
      equilibrium constants, the rate constants of the limiting velocity steps, and the
      concentration of substrate ([S]). Different possibilities have been analyzed from
      an equation written to emphasize that v = f([X]) is, in general and at a fixed
      [S], a hyperbolic function. Formulas for Su (the value of [S], different from
      zero, at which v is unaffected by the modifier) and v(su) (v at that particular
      [S]) were deduced. In Lineweaver-Burk plots, the straight lines related to
      different [X] generally cross in a point (P) with coordinates (Su, v(su)). In
      certain cases, point P is located in the first quadrant which implies that X acts
      as activator, as inhibitor, or has no effect, depending on [S]. Furthermore, we
      discuss: (1) the apparent Vmax and Km displayed by the enzyme in different
      situations; (2) the degree of effect (inhibition or activation) observed at
      different concentrations of substrate and modifier; (3) the concept of Ke, a
      parameter that depends on the concentration of substrate and helps to evaluate
      the effect of the modifier: it equals the value of [X] at which the increase or
      decrease in the reaction rate is half of that achieved at saturating [X].
      Equations were deduced for the general case and for particular situations, and
      used to obtain computer-drawn graphs that are presented and discussed. Formulas
      for apparent Vmax, Km and Ke have been written in a way making it evident that
      these parameters can be expressed as pondered means.

PMID- 10961699
TI  - An easy procedure to transform the ratio of two polynomials of first degree into
      Michaelis-Menten-type equations. Application to the ordered Uni Bi enzyme
      mechanism.
AB  - It is not always clear that some equations affected by complicated factors can,
      actually, be interpreted as a ratio of two polynomials of first degree and so
      that they can be, in general, represented by rectangular hyperbolas. In this
      paper we present an easy procedure to rearrange those equations into Michaelis
      Menten-type equations and so to make the aspects of these rectangular hyperbolas
      more clear, particularly for researchers familiar with general biochemistry. As
      an example, the method is applied to transform the classical rate equation of the
      Cleland's Ordered Uni Bi enzyme mechanism.

PMID- 10961700
TI  - Carbohydrate malabsorption syndromes and early signs of mental depression in
      females.
AB  - Fructose and lactose malabsorption are characterized by impaired duodenal
      fructose transport or by the deficiency of mucosal lactase, respectively. As a
      consequence, the nonabsorbed saccharides reach the colon, where they are broken
      down by bacteria to short fatty acids, CO2, and H2. Bloating, cramps, osmotic
      diarrhea, and other symptoms of irritable bowel syndrome are the consequence and
      can be seen in about 50% of carbohydrate malabsorbers. We have previously shown
      that fructose as well as lactose malabsorption were associated with signs of
      mental depression. It was therefore of interest to investigate possible
      interactions between fructose and lactose malabsorption and their influence on
      the development of signs of depression. In all, 111 otherwise healthy volunteers
      (81 females and 30 males) with gastrointestinal complaints were analyzed by
      measuring breath H2 concentrations after an oral dose of 50 g lactose and of 50 g
      fructose one week apart. They were classified as normals, isolated fructose
      malabsorbers, isolated lactose malabsorbers, and combined fructose/lactose
      malabsorbers. All patients filled out a Beck's depression inventory
      questionnaire. Twenty-five individuals (22.5%) were neither fructose nor lactose
      malabsorbers (group 1), 69 (62.2%) were only fructose malabsorbers (group 2), 4
      (3.6%) were only lactose malabsorbers (group 3), and 13 (11.7%) presented with
      fructose and lactose malabsorption together (group 4). Isolated fructose
      malabsorption and combined fructose/lactose malabsorption was significantly
      associated with a higher Beck's depression score. Further analysis of the data
      show that this association was strong in females (P < 0.01), but there was no
      such association between carbohydrate malabsorption and early signs of depression
      in males. In conclusion, the data confirm that fructose malabsorption may play a
      role in the development of mental depression in females and additional lactose
      malabsorption seems to further increase the risk for development of mental
      depression.

PMID- 10961701
TI  - Determination of biomechanical properties in guinea pig esophagus by means of
      high frequency ultrasound and impedance planimetry.
AB  - Impedance planimetry and high-frequency ultrasound were used to determine
      circumferential stress and strain from measurements of luminal cross-sectional
      area and wall thickness during balloon distension of the guinea pig esophagus in
      vitro (N = 30). The excised esophagus was mounted on two plastic tubes in an
      organ bath containing oxygenated calcium-free Krebs-Ringer solution with 10(-2) M
      MgCl2 to abolish smooth muscle contractile activity. One of the plastic tubes was
      movable in order to stretch the esophagus longitudinally by 15% (elongated
      state). The impedance planimetry probe was placed with the balloon inside the
      lumen of the esophagus. A 20-MHz ultrasound transducer was mounted above the
      esophagus and provided scans in the transverse and longitudinal directions. The
      luminal cross-sectional area at the highest applied pressure of 2.9 kPa was 13.3
      +/- 0.3 mm2 in the resting state. In the elongated state the luminal cross
      sectional area at the highest pressure was 12.5 +/- 0.1 mm2 (P < 0.02). The wall
      thickness decreased from 990 +/- 21 microm at 0 kPa to 640 +/- 9 microm at 2.9
      kPa at in vitro length. In the elongated state, the values were 940 +/- 32 microm
      to 480 +/- 13 microm (P < 0.01). The stress-strain relation was exponential
      (sigma = alpha(ebetaepsilon - 1), r2 > 0.98, P < 0.01). The circumferential
      elastic modulus calculated at a Green strain of 0.95 was 44.5 +/- 10.5 kPa in the
      in vitro state and 81.7 +/- 13.1 kPa in the elongated state. The elastic modulus
      differed between the resting and elongated states (P < 0.02).

PMID- 10961702
TI  - Diurnal motor activities of the esophagus in conscious dogs.
AB  - Diurnal motor activities of the upper, middle, and lower thirds of the thoracic
      esophagus, the lower esophageal sphincter, and the gastric body were recorded in
      six conscious dogs, using extraluminal force transducers. The motor activities of
      the thoracic esophagus and the lower esophageal sphincter were divided into three
      major motility patterns: feeding, digestive, and interdigestive. Each motility
      pattern was basically composed of repetitive bursts of contractions that were
      clearly classified into type I and II according to their contractile properties.
      Type I bursts were peristaltic contractions initiated at the upper thoracic
      esophagus and sequentially propagated distally to include the sphincter.
      Propagation velocity and duration of type I contractions were similar in all
      three motility patterns, and these contractions never were propagated into the
      stomach. Type II bursts were nonperistaltic simultaneous contractions of the
      thoracic esophagus and lower sphincter appearing synchronously with phase III of
      gastric interdigestive migrating contractions. Amplitude and duration of type II
      contractions were maximal at the sphincter, suggesting initiation at that site.
      In nonfeeding patterns, type I contractions would clear the esophagus of refluxed
      gastric contents, while type II contractions would prevent reflux.

PMID- 10961703
TI  - Function of hollow viscera in children with constipation and voiding
      difficulties.
AB  - We wished to investigate the urodynamic characteristics and colonic motility in a
      group of children with severe chronic constipation and lower urinary tract
      symptoms. We performed colonic manometry using an endoscopically placed catheter.
      The urodynamic studies consisted of cystometry, electromyography of the external
      urethral sphincter, measurement of urinary flow rate, and urethral pressure
      profile. We found abnormal colonic motility in all patients. Findings included:
      absent gastrocolonic response (N = 8), absent high-amplitude propagated
      contractions (HAPCs) (N = 4), and abnormal propagation of HAPCs (N = 7).
      Urodynamic features were abnormal in 10 children. Findings included: uninhibited
      bladder contractions (N = 6), hypertonic bladder (N = 2), sphincter dyssynergy (N
      = 2), small capacity bladder (N = 1). In all children constipation improved, in
      three after a partial colectomy. Urinary symptoms persisted. We conclude that
      some children with severe constipation may have a neuropathy affecting both the
      colonic and lower urinary tracts systems. In this group of patients treatment of
      constipation does not result in resolution of urinary symptoms.

PMID- 10961704
TI  - Colonic motor function in humans is not affected by gender.
AB  - Functional abdominal pain, including the irritable bowel syndrome, is more common
      in females. Our aim was to determine if differences in motility or biomechanical
      properties of the colon could account for this gender difference. In 18 healthy
      subjects (nine males), a catheter assembly incorporating a balloon and perfused
      side holes, connected to a barostat, was positioned in the left colon. The system
      was used to determine compliance, sensation in response to phasic balloon
      distension, and changes in motor activity and tone in response to a meal. There
      was no significant difference in any of these variables between males and
      females. We conclude that there is no gender difference in colonic motor function
      or sensation to balloon distension. The increased prevalence of irritable bowel
      syndrome in females may be related to psychosocial factors rather than
      differences in colonic motor function.

PMID- 10961705
TI  - Gastric emptying rate of solids is reduced in a group of ileostomy patients.
AB  - Feedback inhibition from the colon acts as a potent inhibitor of gastrointestinal
      motility via an array of gut peptides and neural pathways. The effect of total
      colonectomy on gastric emptying was assessed in five healthy ileostomy patients
      (<5 cm ileal resection) and five matched controls. Each subject consumed two
      isoenergetic test meals of contrasting fat-carbohydrate ratio in random order.
      Emptying of solids was measured using the [13C]octanoic acid breath test, and
      liquid emptying was assessed after oral dosing with paracetamol. Ileostomist
      subjects exhibited an increased half-emptying time for solids (P = 0.047), which
      included components of an increased gastric lag time (P = 0.004) and a reduction
      in the linear emptying rate (P = 0.003). There was no difference in the pattern
      of liquid emptying between subject groups. In conclusion, the gastric emptying
      rate of solids was reduced in ileostomy patients compared with controls.

PMID- 10961706
TI  - Transient lower esophageal sphincter relaxations and esophageal body muscular
      contractile response in reflux esophagitis.
AB  - In patients with gastroesophageal reflux disease (GERD), transient lower
      esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid
      reflux than in normals. The role of esophageal tone during gastroesophageal
      reflux events is unknown. We studied the tonic motor activity in the body of the
      esophagus during TLESRs with and without acid reflux in 11 patients with erosive
      esophagitis and compared the results with those previously obtained in healthy
      subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above
      a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm
      above the sleeve to induce an esophageal tonic contraction [artificial high
      pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly
      higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P <
      0.05). TLESRs per se were not associated with an inhibition or increase in
      esophageal body contractility, which, however, changed substantially immediately
      after reflux. In patients with esophagitis the esophageal body tonic
      contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05).
      Esophageal contractions during TLESRs traveled down the esophagus in 77% of the
      instances in patients vs 96.5% in controls (P < 0.05). In conclusion,
      gastroesophageal reflux during TLESRs was more frequently associated with
      inhibition of esophageal body tonic contractility in patients with esophagitis
      than in normals. The different response of the esophageal body to reflux observed
      in GERD patients may partially contribute to the higher prevalence of reflux
      during TLESRs in these patients.

PMID- 10961707
TI  - Natural history of HIV-associated esophageal disease in the era of protease
      inhibitor therapy.
AB  - The aim of this study was to determine the outcome of patients with HIV
      associated esophageal disease refractory to empiric antifungal therapy, both
      before and after the introduction of protease inhibitors. We reviewed the medical
      records of 629 consecutive HIV-infected patients with odynophagia, dysphagia, or
      both esophageal symptoms refractory to at least one week of empiric antifungal
      therapy who underwent endoscopy between January 1992 and January 1997 at Bellevue
      Hospital Center. Endoscopy identified an etiology in 96.2% of patients, with
      cytomegalovirus ulcers (40.0%) and idiopathic ulcers of the esophagus (26.67%)
      being the most common lesions found. Overall, 91.4% of patients had a response to
      disease-specific therapy. In patients taking protease inhibitors, recurrent
      symptoms were less common (26.5% vs 36.7%, P = 0.03) and median survival was
      longer (172 vs 125 weeks. P = 0.006) than in those who were not treated with
      these potent antiretroviral medications. Protease inhibitors have had a positive
      impact on the outcome of HIV-associated esophageal disease.

PMID- 10961708
TI  - Altered gastrin regulation in mice infected with Helicobacter felis.
AB  - Altered gastrin expression associated with Helicobacter pylori infection may
      contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man,
      but gastrin has not been investigated in a murine model of Helicobacter
      infection. C57BL/6 mice were inoculated with Helicobacter felis and examined
      after 4-21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA,
      and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six
      weeks after infection to 57% and 23%, respectively, of uninfected control values.
      Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25%
      decrease at six weeks after infection. Similar reductions were noted in G and D
      cell numbers, resulting in a decrease in the G/D cell ratio after mice were
      infected with H. felis. Infected animals also showed a loss of parietal and chief
      cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to
      an early suppression of G cell number and gastrin mRNA. These changes precede an
      alteration in somatostatin cell number and mRNA and, coupled with reductions in
      parietal and chief cells, may contribute both to severe impairment of gastric
      acid output and the potential for carcinogenic processes.

PMID- 10961709
TI  - Effect of Helicobacter pylori eradication on 24-hour gastric pH and duodenal
      gastric metaplasia.
AB  - Published data on the regression of the extent of duodenal gastric metaplasia
      (DGM) after the eradication of Helicobacter pylori infection and the
      normalization of the organism-induced alterations in gastric physiology are
      scanty and controversial. Therefore, we decided to assess the circadian pattern
      of gastric acidity and the degree of DGM before and one year after H. pylori
      eradication in a group of duodenal ulcer patients. Fifteen consecutive H. pylori
      positive patients with endoscopically proven duodenal ulcer were recruited for
      this study. The diagnosis of H. pylori infection was based on CLO-test and
      histology, and DGM was assessed on four bulb biopsies taken before and one year
      after H. pylori eradication. At the same time, gastric pH was measured by 24-hr
      continuous intraluminal recording. H. pylori eradication was ascertained by means
      of concomitant negative CLO-test and histology performed both four weeks after
      the end of the eradicating treatment and at the one-year endoscopic control.
      After successful cure, all patients discontinued any antiulcer medication. The
      mean 24-hr gastric pH was 1.7 +/- 0.4 before and 1.6 +/- 0.4 after one year of H.
      pylori eradication (P = 0.75). DGM improved in three cases, worsened in four
      cases, and was unchanged in eight cases at the one-year control (P = 0.87). No
      correlation was found between 24-hr gastric pH and DGM (P = NS) both at baseline
      and one year after eradication. Our results show that neither circadian gastric
      acidity nor DGM change significantly one year after H. pylori eradication in
      duodenal ulcer patients. Thus, the disappearance of H. pylori infection does not
      determine any increase in gastric pH and any reversal of gastric-type epithelium
      in the duodenum.

PMID- 10961711
TI  - Selection of lower cutoff point of [13C]urea breath test is helpful to monitor H.
      pylori eradication after proton pump inhibitor-based triple therapy.
AB  - Our objectives were to test the efficacy of [13C] urea breath test (UBT) for H.
      pylori infection in patients before and after proton pump inhibitor (PPI) based
      triple therapy, and thus to trace the optimal cutoff value of UBT to monitor H.
      pylori eradication; and to analyze the histologic bacterial density and
      distribution of H. pylori in patients with equivocal UBT. A total of 441
      dyspeptic cases patients enrolled and completed the study design, including 120
      noninfected and 321 H. pylori-infected patients. All 441 cases had received the
      same protocol of UBT. in which the baseline and 15-min gas samples after
      ingestion of 100 mg 13C-labeled urea were analyzed for excess 13CO2/12CO2 ratio
      (ECR). In addition, a first endoscopy was performed in each patient to evaluate
      the initial status of H. pylori by culture and histology. Of the 321 H. pylori
      infected patients, 286 received a second endoscopy and a second UBT six weeks
      after completing any one of four regimens of the PPI-based triple therapy to
      document the success of H. pylori eradication. During both sessions of endoscopy,
      topographic gastric biopsies for histology were sampled to evaluate the
      distribution and density of H. pylori. Based on the diagnostic standard by
      culture and histology, the sensitivity and specificity of the first UBT achieved
      most optimally was 97.5% and 96.7%, respectively, by setting the cutoff point of
      ECR at 4.0. In contrast, using the same cutoff point of 4.0, the sensitivity and
      specificity of the second UBT in patients after therapy achieved just 80% and
      97.6%, respectively. By applying cutoff points downward of 4.0, 3.5, 3, and 2.5
      for the second UBT, the sensitivity was elevated to 80%, 82.8%, 88.6%, and 94.3%,
      respectively, while the specificity was preserved at more than 95.2%. The overall
      eradication rate of H. pylori was 87.8% (251/286). Seven of 35 patients with
      failure of therapy had equivocal ECR at the second UBT (range 2-5), and this
      accounted for the false negative result. All seven patients had low bacterial
      densities, and three patients had bacteria distributed only in high body near the
      cardia. In conclusion, selection of a lower cutoff value of ECR at 2.5 is helpful
      to maintain the diagnostic accuracy of UBT for monitoring the H. pylori
      eradication. The equivocal ECR of UBT after therapy would be related to the low
      bacterial load and its distribution.

PMID- 10961710
TI  - Prevalence of gastroduodenitis and Helicobacter pylori infection in a general
      population sample: relations to symptomatology and life-style.
AB  - Some benign and malignant diseases develop on the background of chronic gastritis
      or duodenitis. The present study was performed in order to determine the
      magnitude of these background changes with relations to symptomatology and life
      style in the general population. Examinations were performed in 501 volunteers
      (age 35-85 years). Fifty percent had gastritis; this was associated with H.
      pylori in 87%. H. pylori-negative gastritis was associated with regular use of
      NSAIDs [odds ratio 3.8 (1.6-9.9)]. Duodenitis, observed in 32%, was associated
      with H. pylori infection [odds ratio 2.3 (1.3-4.6)], previous cholecystectomy
      [odds ratio 3.6 (1.1-16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4
      7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol
      consumption. The rate of digestive symptoms did not differ between subjects with
      and without uncomplicated gastritis or duodenitis. In conclusion, half of this
      adult population had gastritis strongly associated with H. pylori infection.
      Gastritis without H. pylori infection was frequently associated with regular
      NSAID intake. One third had duodenitis, which was associated with H. pylori
      infection as well as with regular use of NSAIDs and previous cholecystectomy.
      Digestive symptoms were not overrepresented in uncomplicated gastritis or
      duodenitis.

PMID- 10961713
TI  - Effects of chronic administration of Helicobacter pylori extracts on rat gastric
      mucosal microcirculation in vivo.
AB  - The mechanisms by which Helicobacter pylori contributes to gastroduodenal injury
      are unclear. We have previously described platelet aggregation within rat gastric
      mucosal microcirculation following acute administration of H. pylori extracts.
      However, leukocyte activation was not observed. This study aimed to determine
      whether chronic administration of H. pylori could induce leukocyte activation.
      Rats were gavaged with either H. pylori or E. coli extracts or with distilled
      water three times daily at three-day intervals. Acridine red was used to
      quantitate gastric mucosal leukocyte/platelet activity using fluorescent in vivo
      microscopy. Further animals received additional acute H. pylori after 1 hr and
      recordings were made for a further 1 hr. Significant numbers of "flyers,"
      "rollers," and adherent leukocytes were observed throughout the study in H.
      pylori animals. Only adherent leukocytes were observed following E. coli. Acute
      H. pylori induced a further significant increase in adherent leukocytes.
      Significant platelet thrombi were also present in H. pylori-treated animals. In
      conclusion, earlier studies demonstrated platelet aggregation but no leukocyte
      activation, which is in contrast to the current chronic studies. Platelet
      activation may be the initial response to H. pylori and involved in recruitment
      of leukocytes. These activated cells may contribute to the development of gastric
      mucosal damage.

PMID- 10961712
TI  - Increased macrophage infiltration of gastric mucosa in Helicobacter pylori
      infected children.
AB  - The purpose of the study was to quantify gastric mucosal macrophages and define
      their association with the histopathologic features of stomach biopsies obtained
      from Helicobacter pylori-infected and uninfected children. Endoscopically
      obtained gastric biopsies from symptomatic children were independently evaluated
      by two groups of pathologists. Thirty children were evaluated; 14 were H. pylori
      infected. H. pylori positivity was determined by hematoxylin and eosin (H&E),
      Giemsa, Warthin-Starry and an H. pylori-specific immunoperoxidase stain. A
      macrophage-specific, KP-1, immunoperoxidase stain was used to quantify positive
      cells. Inflammatory cell infiltrates were graded by severity with scores of mild
      to severe. Increased numbers of gastric mucosal macrophages were observed in
      biopsies of H. pylori-infected versus uninfected children (P < 0.05) and
      correlated with gastritis severity. The role of this inflammatory cell the in
      persistence of gastric mucosal inflammation in H. pylori infection warrants
      further study to develop targeted immunotherapeutic strategies.

PMID- 10961714
TI  - Acid secretory changes in streptozotocin-diabetic rats: different responses to
      various secretagogues.
AB  - We examined gastric acid secretion in response to various stimuli in
      streptozotocin (STZ) induced diabetic rats and characterized the alteration of
      acid secretory responses in diabetic conditions. Animals were injected STZ (70
      mg/kg, intraperitoneally) and used after five weeks of diabetes with blood
      glucose >350 mg/dl. Under urethane anesthesia, the experiment was performed in a
      chambered stomach or a whole stomach preparation, and the acid secretion was
      measured at pH 7.0 using a pH-stat method and by adding 100 mM NaOH. The acid
      secretion was stimulated by intravenous infusion of either histamine (4
      mg/kg/hr), pentagastrin (60 microg/kg/hr), or carbachol (20 microg/kg/hr) or by
      intraluminal application of peptone solution (4%), or vagal electrical
      stimulation (2 msec, 3 Hz, 0.5 mA). In normal rats, acid secretion was increased
      in response to either histamine, pentagastrin, carbachol, peptone, or electrical
      vagal stimulation. In STZ diabetic rats, however, changes in acid secretion
      varied depending on the stimuli; the acid response to histamine remained
      unchanged, but the responses to vagal electrical stimulation or pentagastrin and
      carbachol were significantly decreased or enhanced, respectively, as compared to
      normal rats. Likewise, the acid response to peptone was also markedly enhanced in
      STZ-diabetic rats, and this response was significantly blocked by atropine and
      YM022 (a CCKB/gastrin antagonist) as well as famotidine in both normal and
      diabetic rats. Both pentagastrin and carbachol increased the luminal release of
      histamine in normal rats, and these responses were significantly augmented in STZ
      diabetic rats. The altered acid response and histamine release induced by
      pentagastrin in STZ diabetic rats were partially reversed by daily injection of
      insulin. These results suggest that STZ-diabetic rats showed different changes in
      gastric acid secretion in response to various stimuli. The increased acid
      secretory response may be associated with an enhanced release of mucosal
      histamine, while the decreased response may be due to vagal neuropathy.

PMID- 10961715
TI  - In vivo selectivity of nonsteroidal antiinflammatory drugs and gastrointestinal
      ulcers in rats.
AB  - The aim of the present work was to study in vivo COX-2-COX-1 selectivity of 16
      nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in
      two in vivo experimental models. Indomethacin, ibuprofen, nimesulide,
      aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol,
      piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and
      ketorolac were administered to female Wistar rats (N = 10 each group). In
      experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II,
      NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer
      area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic
      gastric fundus area (65%) and erosive intestinal area (182 mm2), "in vivo" the
      NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where
      also ibuprofen and paracetamol not given neotrophilic infiltration. In
      conclusion, COX-2-COX-1 selectivity was demonstrated in vivo with the drugs
      aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.

PMID- 10961716
TI  - Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a
      preferential COX-2 inhibitor in the stomach.
AB  - The relative risk of development of peptic ulcer with the use of nonsteroidal
      antiinflammatory drugs (NSAIDs) has been reported to increase when these drugs
      are administered in combination with steroids. We investigated the ulcerogenic
      potential of a combination of NSAIDs and steroids in rats and the underlying
      pathogenic mechanisms. Indomethacin alone produced gastric lesions, and the
      severity of the lesions markedly increased with concomitant administration of
      prednisolone. However, nimesulide, even in excessive doses, did not produce any
      gastric lesions, regardless of concomitant administration with prednisolone.
      Furthermore, we showed that the ulcerogenic potential of indomethacin
      administered in combination with prednisolone may be related to the induction of
      physiological changes, such as endogenous prostaglandin deficiency, an increase
      in neutrophil activation, and gastric hypermotility, by indomethacin and
      alteration of normal epithelial renewal by the steroid. These results suggest
      that the ulcerogenic potential of preferential a COX-1 inhibitor increases
      following concomitant administration with a steroid, whereas, nimesulide, a
      preferential COX-2 inhibitor, is nonulcerogenic, even when administered
      concomitantly with a steroid, and is therefore a clinically useful
      antiinflammatory agent.

PMID- 10961717
TI  - Development of a multiple-marker RT-PCR assay for detection of micrometastases of
      hepatocellular carcinoma.
AB  - We investigated the expression of several candidate gene markers: MAGE-1, MAGE-3,
      cytokeratin-20 (CK-20), and alpha-fetoprotein (AFP) in tumor tissue and blood
      specimens from patients with hepatocellular carcinoma to develop a multiple
      marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for
      detection of micrometastasis in circulation. In 24 tumor specimens, the
      positivity for MAGE-1, MAGE-3, AFP, and CK-20 genes was 71, 67, 88, and 79%
      respectively, and all specimens expressed at least one marker. Although AFP and
      CK-20 transcripts were also detected in corresponding noncancerous liver
      specimens, none of the 22 corresponding normal specimens or seven normal livers
      were positive for MAGE-1 or MAGE-3 transcripts. In addition, MAGE-1 and MAGE-3
      gene transcripts were not detected in any peripheral blood specimens from 31
      normal healthy volunteers. MAGE-1, MAGE-3, and AFP transcripts were detected in 9
      (12.7%), 3 (4.8%), and 10 (15.9%) of 71 blood specimens from 11 hepatocellular
      carcinoma patients, respectively, while 19 specimens (26.8%) were positive for at
      least one marker. Our results indicate that a multimarker RT-PCR assay with
      cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a liver
      specific AFP marker may be a promising diagnostic tool for monitoring
      hepatocellular carcinoma patients with better sensitivity and specificity.

PMID- 10961719
TI  - Treatment of chronic hepatitis C with amantadine.
AB  - Hepatitis C is usually treated with interferon or a combination of interferon and
      ribavirin, but these agents have numerous side effects, and interferon must be
      given by injection three time a week. An alternative oral medication would be a
      welcome advance for treating hepatitis C. Amantadine has been reported to have
      the potential to produce viral suppression in patients with hepatitis C. To gain
      further knowledge about the effects of amantadine on hepatitis C, we treated 24
      patients for 3-12 months (average = 5.5 months; median = 4.5 months) with 100 mg
      amantadine twice daily. Twelve patients had stage 3 or 4 fibrosis on biopsy.
      Eleven patients had a fall in viral titer, but complete viral suppression was not
      seen in any patient. Three patients had no viral titer obtained after treatment,
      but their elevated transaminase levels did not change with treatment. Of the 15
      patients with a decrease in enzyme levels, only two patients had normalization.
      Six patients had side effects during the treatment, but in only one was
      amantadine stopped solely because of side effects. Based on these results and a
      literature review, we do not believe amantadine is an effective single agent for
      the treatment of chronic hepatitis C.

PMID- 10961718
TI  - Presence of active hepatitis associated with liver cirrhosis is a risk factor for
      mortality caused by posthepatectomy liver failure.
AB  - The histologic activity of associated hepatitis was examined in 285 patients who
      underwent hepatectomy for hepatocellular carcinoma (HCC), to determine if the
      histologic activity is an independent risk factor for postoperative mortality due
      to liver failure. The proportion of patients with liver cirrhosis who died due to
      liver failure (6/180, 3.3%) was not different from that of patients with chronic
      hepatitis (2/68, 2.9%). However, mortality was higher in patients with liver
      cirrhosis and active hepatitis (4/46, 8.7%) than in those with cirrhosis and
      inactive hepatitis (2/134, 1.5%, P < 0.05). Such difference was not observed in
      the chronic hepatitis group. Multivariate analysis showed that clearance of
      indocyanine green at 15 min (ICGR15) and activity of hepatitis were two
      independent risk factors for postoperative mortality due to liver failure. In
      conclusion, histologic activity of associated hepatitis should be taken into
      account in hepatic resection of HCC in cirrhotic liver, in addition to the
      functional reserve of the liver.

PMID- 10961721
TI  - Chronic liver injury related to use of bentazepam: an unusual instance of
      benzodiazepine hepatotoxicity.
AB  - Liver injury induced by benzodiazepines is rare and is classified as an
      unpredictable or idiosyncratic hepatotoxic reaction. Early reports indicated that
      in most cases the pattern of liver injury was cholestatic. We describe three
      patients with persistent increases in liver transaminase levels after several
      weeks of treatment with bentazepam, a benzodiazepine marketed in Spain for
      anxiety disorders. In all cases withdrawal of the drug was followed by resolution
      of transaminase level abnormalities. A liver biopsy (done in one patient only)
      showed histological evidence of severe chronic active hepatitis. In conclusion,
      these findings, together with two previously published case reports, suggest that
      a benzodiazepine can cause chronic hepatitis and argue in favor of using liver
      function tests to monitor all patients taking bentazepam.

PMID- 10961720
TI  - Early increase of bone resorption in patients with liver cirrhosis secondary to
      viral hepatitis.
AB  - Bone loss is an established complication of cholestatic liver cirrhosis, while
      little is known about bone mass and metabolism in noncholestatic liver cirrhosis.
      The aim of the present study is, therefore, to evaluate bone mass and mineral
      metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone
      mineral density measurement at lumbar and femoral levels and the evaluation of
      bone and mineral metabolism and gonadal function were performed in 31 patients
      with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral
      density values were significantly lower in patients than in healthy volunteers.
      Prevalence and severity of bone loss increased according to the severity of liver
      disease. All serum indices of bone and mineral metabolism and of gonadal function
      showed a similar behavior, but a significant increase of bone resorption was
      present in all Child-Pugh classes. In particular, class A patients showed normal
      mean bone mineral density values but increased serum levels of the telopeptide of
      type I collagen. Liver cirrhosis predisposes to bone loss regardless of the
      presence of cholestasis. The severity of metabolic osteopathy worsens as liver
      function does. The underlying mechanism is represented by an increased bone
      resorption.

PMID- 10961722
TI  - Detection of Helicobacter pylori DNA in human biliary tree and its association
      with hepatolithiasis.
AB  - Recently, several authors have reported that Helicobacter pylori DNA has been
      found in human bile. The aim of this study is to investigate the presence of H.
      pylori in the biliary tree of Koreans, including the bile, biliary epithelium,
      and gallstones. This study analyzed intrahepatic bile, bile duct tissue, and
      gallstones from 43 patients with hepatobiliary disease (PTCS group), gallbladder
      bile and tissue from 23 patients with gallbladder disease (CCT group), and eight
      patients without hepatobiliary disease (control group). H. pylori was examined by
      PCR with two different primers. PCR was positive in 4/43 (9.3%) by 26 kDa protein
      antigen primer and in 5/43 (11.6%) by urease A gene primer in bile from the PTCS
      group. However, in intrahepatic duct tissue, PCR was positive in only one case.
      PCR of gallbladder bile, tissue, and intrahepatic duct stones was negative. Upon
      intrahepatic bile analysis, the pH was significantly lower in PCR-positive than
      in negative cases (P < 0.05). In conclusion, H. pylori DNA may be present in the
      bile when there are certain environmental changes, such as lowered pH; however,
      H. pylori does not colonize the bile duct epithelium. We could find no
      pathogenetic role for H. pylori in the formation of hepatolithiasis.

PMID- 10961724
TI  - Calmodulin regulation of gallbladder ion transport becomes dysfunctional during
      gallstone formation in prairie dogs.
AB  - Gallbladder absorption is increased prior to gallstone formation in prairie dogs
      and may promote cholesterol crystallization. Recent studies indicate that Ca2+
      calmodulin (CaM) tonically inhibits gallbladder electrolyte absorption in prairie
      dogs fed a nonlithogenic diet. We hypothesized that dietary cholesterol alters
      CaM-dependent regulation of gallbladder ion transport, a possible link between
      increased gallbladder absorption and gallstone formation. Gallbladders from
      prairie dogs fed control (N = 24) or 1.2% cholesterol-enriched chow (N = 32) were
      mounted in Ussing chambers. Electrophysiology and ion flux were measured while
      exposing the epithelia sequentially to trifluoperazine (TFP), a CaM antagonist,
      followed by the calcium ionophore A23187. Animals fed the high cholesterol diet
      developed crystals and gallstones in a time-dependent fashion. Mucosal addition
      of 50 microM TFP decreased short-circuit current (Isc), transepithelial
      potential, and tissue conductance in control, crystal, and gallstone animals, but
      the magnitude of its effect was significantly decreased in animals fed
      cholesterol. TFP stimulated mucosa-to-serosa Na+ flux by 6.9 +/- 0.9
      microeq/cm2/hr in control animals but only 3.1 +/- 0.8 microeq/cm2/hr in
      gallstone animals. Similarly, TFP increased mucosa-to-serosa Cl- flux by 11.9 +/-
      1.4 microeq/cm2/hr in controls but only 4.9 +/- 1.4 microeq/cm2/hr in cholesterol
      fed animals. TFP effects were not reversed by A23187, which caused differential
      effects on Isc and ion transport in cholesterol-fed animals. In conclusion, CaM
      mediated inhibition of gallbladder Na+ and Cl- transport is diminished in prairie
      dogs fed cholesterol. We conclude that gallbladder ion transport is partially
      released from basal inhibition during gallstone formation and propose that
      dysfunctional CaM regulation may be a stimulus to increased gallbladder
      absorption.

PMID- 10961723
TI  - Role of phospholipase A2 in cholesterol gallstone formation is associated with
      biliary phospholipid species selection at the site of hepatic excretion: indirect
      evidence.
AB  - Phospholipase A2 plays a role in cholesterol gallstone development by hydrolyzing
      bile phospholipids into lysolecithin and free fatty acids. Lysolecithin and
      polyunsaturated free fatty acids are known to stimulate the synthesis and/or
      secretion of gallbladder mucin via a prostanoid pathway, leading to enhancing
      cholesterol crystal nucleation and growth, and therefore, the action of
      phospholipase A2 is associated, in part, with bile phospholipid fatty acid. To
      clarify this hypothesis, we evaluated the effect on bile lipid metastability in
      vitro of replacing phospholipids with lysolecithin and various free fatty acids.
      Supersaturated model biles were created with an identical composition
      (cholesterol saturation index, 1.8; egg yolk lecithin, 34 mM; taurocholate, 120
      mM; cholesterol, 25 mM) except for 5%, 10%, or 20% replacement of egg yolk
      lecithin with a combination of palmitoyl-lysolecithin and a free fatty acid
      (palmitate, stearate, oleate, linoleate, or arachidonate), followed by time
      sequentially monitoring of vesicles and cholesterol crystals using
      spectrophotometer and video-enhanced differential contrast microscopy.
      Replacement with hydrophilic fatty acids (linoleate and arachidonate) reduced
      vesicle formation and promoted cholesterol crystallization, whereas an enhanced
      cholesterol-holding capacity was evident after replacement with hydrophobic fatty
      acids (palmitate and stearate). These results indicate that the effect of
      phospholipase A2 on bile lithogenecity is modulated by the fatty acid species in
      bile phospholipids, and therefore, that the role of phospholipase A2 in
      cholesterol gallstone formation is dependent, in part, on biliary phospholipid
      species selection at the site of hepatic excretion.

PMID- 10961725
TI  - Enhancement of bile acid pool size, synthesis and secretion by epomediol in the
      rat.
AB  - Epomediol is a terpenoid compound that has been reported to reverse 17alpha
      ethinylestradiol-induced cholestasis and to have a choleretic effect related to
      the biliary secretion of epomediol glucuronide. The aim of this study was to
      investigate the contribution of changes in bile acid metabolism to epomediol
      induced effects on bile formation. Twenty-four-hour bile collections were
      performed in animals that had received intraperitoneal epomediol for five days at
      100 mg/kg daily. Epomediol-treated rats had a 24% larger bile acid pool and 28%
      greater bile acid synthesis than controls when measured by the "washout"
      technique. There was no change in the fractional turnover rate and the cycling
      frequency of the pool. Both basal bile flow and bile acid secretion were
      significantly increased (+42% and +74%, respectively). Linear regression analysis
      between bile flow and bile acid secretion revealed that both bile acid-dependent
      fraction and bile acid-independent fraction were significantly increased (+40 and
      +27, respectively), with no change in the choleretic capacity of bile acids.
      Cholesterol secretion was increased by 42%, but there were no significant
      differences in phospholipid secretion. Cholesterol 7alpha-hydroxylase and HMG-CoA
      reductase activities were significantly higher in epomediol-treated rats (+39%
      and +97%, respectively). The activities of NADPH-cytochrome c reductase and
      aniline hydroxylase were also significantly elevated (+26% and +64%,
      respectively). It is concluded that epomediol treatment expands the bile acid
      pool through an enhanced bile acid synthesis. Choleresis induced by the drug is
      partly related to the increase in bile acid secretion.

PMID- 10961727
TI  - Site of bismuth absorption from bismuth subsalicylate: implications for treatment
      of colonic conditions.
AB  - Poorly absorbed bismuth preparations may benefit a variety of chronic colonic
      conditions including ulcerative colitis. Bismuth-induced neurotoxicity is a
      potential complication of the chronic use of these preparations, and a less
      absorbable form of bismuth is needed. If bismuth absorption occurs primarily in
      the upper gut, a delayed-release bismuth preparation could reduce absorption. We
      studied the site of bismuth absorption from bismuth subsalicylate (BSS) in rats.
      For 15 days, BSS (50 mg/day) was ingested or infused directly into the cecum via
      a chronically implanted cannula. Oral BSS resulted in serum and urine bismuth
      levels many times higher (3.5 +/- 0.3 microg/liter and 1,570 +/- 286 microg/g
      creatinine, respectively) than with cecal administration (undetectable (<1.5
      microg/liter) and 75 +/- 25 microg/g creatinine). Thus, bismuth absorption from
      BSS occurred almost entirely in the upper gut. These findings provide a rationale
      for a similar study of delayed-release bismuth preparations in humans.

PMID- 10961726
TI  - Binding of hydrogen sulfide by bismuth does not prevent dextran sulfate-induced
      colitis in rats.
AB  - Several lines of evidence suggest that ulcerative colitis could be caused by
      excessive bacterial production of H2S in the colon. A rodent model of colitis
      involves the feeding of nonabsorbable, carbohydrate-bound sulfate in the form of
      dextran sulfate or carrageenan. The observation that metronidazole blocks the
      development of this colitis suggested that the injurious agent could be a sulfur
      containing compound (such as H2S) that is released during the bacterial
      metabolism of the nonabsorbed sulfate. We tested this possibility by feeding rats
      dextran sulfate, with or without bismuth subsalicylate, a compound that avidly
      binds H2S. Bismuth subsalicylate reduced the fecal release of H2S in dextran
      sulfate-treated rats to values well below that of controls. Nevertheless, all the
      animals developed colitis. We conclude that excessive H2S production does not
      play a role in the dextran sulfate model of colitis.

PMID- 10961728
TI  - Collagenous colitis treated successfully with bismuth subsalicylate.

PMID- 10961730
TI  - Saccharomyces boulardii in maintenance treatment of Crohn's disease.
AB  - The possible role of Saccharomyces boulardii, a nonpathogenic yeast with
      beneficial effects on the human intestine, in the maintenance treatment of
      Crohn's disease has been evaluated. Thirty-two patients with Crohn's disease in
      clinical remission (CDAI < 150) were randomly treated for six months with either
      mesalamine 1 g three times a day or mesalamine 1 g two times a day plus a
      preparation of Saccharomyces boulardii 1 g daily. Clinical relapses as assessed
      by CDAI values were observed in 37.5% of patients receiving mesalamine alone and
      in 6.25% of patients in the group treated with mesalamine plus the probiotic
      agent. Our results suggest that Saccharomyces boulardii may represent a useful
      tool in the maintenance treatment of Crohn's disease. However, in view of the
      product's cost, further controlled studies are needed to confirm these
      preliminary data.

PMID- 10961729
TI  - Antigen uptake and trafficking in human intestinal epithelial cells.
AB  - Primary intestinal epithelial cells, human colonic adenocarcinoma cell lines (DLD
      1, Caco-2, and HT-29), and monocytes were used as model systems to study antigen
      uptake, antigen-presenting cell properties, as well as the kinetics of antigen
      uptake in intestinal epithelial cells (IEC). Intracellular staining of
      fluoresceinated tetanus toxoid was not evident in the IEC until after 30 min of
      incubation at 37 degrees C, whereas in monocytes intracellular punctate staining
      of fluoresceinated tetanus toxoid was evident after 5 mins. In polarized Caco-2
      cells antigen could be internalized at both the apical and basolateral surfaces
      with polarized transport. When analyzed by electron microscopy, gold-labeled
      tetanus toxoid was internalized and found within endosomes and multivesicular
      bodies, but not within the lysosomal compartments by 60 min. By 2 hrs, gold
      labeled tetanus toxoid was evident in the secondary lysosomes. These results
      demonstrate that tetanus toxoid follows an endocytic pathway in intestinal
      epithelial cells and that the kinetics of antigen uptake is slower than that of
      conventional antigen-presenting cells.

PMID- 10961731
TI  - Inflammatory bowel diseases are not associated with major hereditary conditions
      predisposing to thrombosis.
AB  - Patients with inflammatory bowel diseases (IBD) are at increased risk for
      thromboembolic complications. Our aim was to evaluate whether the increased risk
      for thrombosis in IBD could be due to a genetic association of IBD with
      hereditary prothrombotic conditions. In all, 102 IBD patients (51 with ulcerative
      colitis and 51 with Crohn's disease) with no history of thrombosis and 204
      matched normal subjects were enrolled. DNA specimens were evaluated by PCR and
      restriction fragment length polymorphism for factor V Leiden, methylene
      tetrahydrofolate reductase (MTHFR) and prothrombin gene mutations. In IBD
      patients and matched controls the observed allele frequencies were similar, being
      1.5% and 1.2% for factor V Leiden gene mutation, 1.1% and 0.7% for prothrombin
      gene mutation, and 45.1% and 47.4% for MTHFR gene mutation, respectively. These
      rates also were not significantly different when patients were analyzed according
      to age and sex distribution, diagnosis, and extension and clinical type of
      disease. In conclusion, our study shows no association between IBD and the most
      frequent hereditary prothrombotic conditions. Other factors should be evaluated
      in order to understand the mechanisms underlying the thrombotic risk of IBD.

PMID- 10961732
TI  - Celiac disease and autoimmune endocrine disorders.

PMID- 10961733
TI  - Involvement of luminal bacteria, heat shock protein 60, macrophages and
      gammadelta T cells in dextran sulfate sodium-induced colitis in rats.
AB  - The in vivo immunological events in dextran sulfate sodium (DSS) -induced colitis
      were evaluated. Rats were fed water (control) or 5% DSS. Colonic sections were
      assessed by light microscopy, Gram stain, immunohistochemistry, and electron
      microscopy. A progressive decline in number and increase in fragmentation of
      bacteria in the colonic lumen was observed over time. Luminal bacteria were the
      first to show heat shock protein 60 (HSP60) staining (day 3). Macrophages in
      close proximity to these bacteria were next to show such staining (day 6), and
      finally the damaged epithelial cells when colitis became severe (day 15).
      Ultrastructural assessment showed cell-cell contact interactions between
      macrophages and dendritic gammadelta T cells. An increase in the number of
      gammadelta T cells and ED1-positive macrophages in the affected colonic tissue
      over time was documented. These results suggest colonic bacteria, host
      macrophages, and gammadelta T cells play specific roles in the immunological
      reactions in DSS-induced colitis, possibly via an HSP60-mediated mechanism.

PMID- 10961734
TI  - Specific preinduction of 60-kDa heat shock protein (chaperonin homolog) by TRH
      does not protect colonic mucosa against acetic acid-induced lesion in rats.
AB  - In order to study the cytoprotective function of colonic heat shock proteins
      (HSPs) in vivo, the effect of specific preinduction of HSP60 by thyrotropin
      releasing hormone (TRH) administration on the development of acetic acid-induced
      colonic mucosal lesion was investigated. Expression of 60-kDa, 72-kDa, and 90-kDa
      heat shock proteins (HSP60, HSP72, and HSP90, respectively) in rat colonic mucosa
      was investigated by western blot and immunohistochemical analyses before and
      after TRH administration. Following pretreatment with or without TRH
      administration, the rats received intrarectal infusion of 5% acetic acid. The
      colonic mucosal damage was macroscopically evaluated 24 hr after the intrarectal
      infusion of acetic acid. Expression of HSP60 was significantly increased by TRH
      administration in the colonic mucosa, whereas HSP72 and HSP90 did not increase.
      Immunohistochemical study also showed a significant increase in HSP60 in colonic
      mucosal cells, especially at the surface of the colonic mucosa after TRH
      administration. No histopathologic alteration was observed in the colonic mucosa
      after TRH administration. The colonic mucosal damage caused by intrarectal
      infusion of 5% acetic acid was not prevented by preinduction of HSP60. We
      demonstrated that specific preinduction of HSP60 by TRH administration did not
      show cytoprotective function in the colonic mucosa, although this protein plays a
      crucial role for cytoprotection in the pancreatic acinar cells. Our results
      indicate that the role of HSP60 may be different in each organ with respect to
      cytoprotection.

PMID- 10961735
TI  - Pharmacological implications of cellular localization of alpha1-adrenoceptors in
      native smooth muscle cells.
AB  - 1. This study examines the cellular localization of alpha1-adrenoceptors and
      demonstrates that binding to intracellular receptive binding sites in native
      smooth muscle cells may influence the pharmacological profile of agonists or
      antagonists. The example tissue studied was rat basilar artery. 2. An alpha1
      adrenoceptor antagonist and fluorescent analogue of prazosin, BODIPY-FL prazosin
      (QAPB) allowed visualization, with high resolution, of both plasma membrane and
      cytosolic binding sites on live native cells, as previously shown in cells
      harbouring recombinant receptors. QAPB-associated fluorescence binding was both
      time- and concentration-dependent in rat basilar smooth muscle cells and affinity
      for alpha1-adrenoceptors was calculated from specific binding curves as 1.1 nM.
      3. Concentration-dependent binding of QAPB detected in smooth muscle cells
      dissociated from rat basilar arteries was composed of diffuse and clustered
      fluorescence. Visually the diffuse component of fluorescence was the more evident
      up to a concentration of 5 nM QAPB. Confocal visualization of an optical section
      through the cell showed that the clustered component was located mainly
      intracellularly. In rat basilar artery smooth muscle cells the intracellular
      binding sites were located in close proximity to the nuclear membrane. 4. 3D
      models of QAPB-associated fluorescence demonstrate that a high proportion of
      effective binding sites are intracellular, showing not only that a high
      proportion of receptors are located inside the cell but also that in this
      location they can bind ligands. This has implications for pharmacological
      analysis in relation to the consequences of intracellular binding per se and for
      differential effects upon the pharmacology of particular ligands according to
      whether they can enter the cell.

PMID- 10961736
TI  - In vitro and in vivo approaches to the characterization of the alpha2
      adrenoceptor.
AB  - 1. In order to more fully understand the role of the alpha2-adrenoceptor in brain
      function, a combination of in vitro and in vivo techniques were utilized
      including radioligand binding, autoradiography, brain microdialysis and antisense
      oligonucleotides. 2. Binding studies showed the tritiated form of the selective
      alpha2-adrenoceptor antagonist, RX821002 (methoxy-idazoxan) labelled an apparent
      single population of sites in rat brain membranes with high affinity (1 nM), for
      which prazosin had low affinity (1107 nM). Similar studies in rabbit brain
      membranes found that prazosin and oxymetazoline were able to displace [3H]
      RX821002 in a biphasic manner indicating the presence of subtypes of alpha2
      adrenoceptors. 3. Receptor autoradiography revealed a distribution of [3H]
      RX821002 binding in rat brain consistent with the labelling of all alpha2
      adrenoceptor subtypes, namely alpha(2A/D-), alpha2B and alpha2C. 4. In rat, in
      vivo brain dialysis experiments demonstrated peripherally administered RX821002
      elevated basal noradrenaline in frontal cortex and also, although to a lesser
      extent, in ventral hippocampus. RX821002 was also able to elevate extracellular
      dopamine in the striatum. 5. A 7-day i.c.v. infusion of an antisense
      oligonucleotide targeting the alpha(2A/D)-adrenoceptor, resulted in a significant
      reduction in the autoradiographic density of [3H]-RX821002 binding in specific
      brain areas, notably the lateral septal nuclei and anterior hypothalamic area. 6.
      Several years of research by our group has extended our knowledge of the
      pharmacology and function of the alpha2-adrenoceptor and has provided evidence of
      the roles of this receptor in the control of monoamine turnover. The successful
      use of antisense technology to knockdown expression of the alpha(2A/D) subtype
      provides future opportunities to explore the physiology of this receptor subtype.

PMID- 10961737
TI  - Prejunctional effects of angiotensin II and bradykinin in the heart and blood
      vessels.
AB  - 1. Angiotensin and bradykinin facilitate the release of noradrenaline from
      sympathetic nerve terminals and cause positive inotropy in rat isolated atria and
      ventricles. The effect of bradykinin was enhanced by the ACE inhibitor,
      ramiprilat. 2. The facilitated release of noradrenaline in rat ventricle by
      bradykinin was blocked by the beta2-receptor antagonist HOE-140. This response is
      also reduced by removing the endocardium, suggesting the release of a mediator
      from the endocardium. 3. The facilitated noradrenaline release by angiotensin II
      and bradykinin was blocked by the angiotensin receptor antagonist saralasin to
      the same extent. In contrast, losartan caused only minor blockade in a range of
      vascular and cardiac tissues. This suggests that angiotensin and bradykinin exert
      these responses by interacting with a prejunctional receptor different from the
      established AT1 subtype. 4. These results suggest that bradykinin mediates
      facilitation of noradrenaline release via the local release of angiotensin onto
      an atypical AT1 receptor.

PMID- 10961738
TI  - The human desipramine-sensitive noradrenaline transporter and the importance of
      defined amino acids for its function.
AB  - 1. This article gives a short overview of the physiology, pharmacology and the
      molecular biology of the human Na+/Cl(-)-dependent noradrenaline transporter
      (hNAT) and its gene. 2. Furthermore, naturally occurring variants of the hNAT are
      described and new results obtained through site-directed mutagenesis of the hNAT
      are presented, which increase our understanding about structural domains and
      amino acids critically involved in substrate, cosubstrate and inhibitor binding
      to the hNAT.

PMID- 10961739
TI  - Review of mechanisms involved in the apparent differential desensitization of
      beta1- and beta2-adrenoceptor-mediated functional responses.
AB  - 1. There has been considerable debate whether responses mediated via beta1- and
      beta2-adrenoceptors (beta1ARs and beta2ARs) display the same degree of
      desensitization after prolonged or repeated exposure to agonists. 2. Examples are
      provided for selective desensitization of functional responses and loss of
      binding sites for beta1ARs. Equally, examples are given of selective
      desensitization and down-regulation involving beta2ARs. 3. This review examines
      whether receptor subtype-selective desensitization of betaAR-mediated responses
      can occur and whether even within the same subtype, there may be tissue-selective
      desensitization. Possible reasons why apparent selectivity of desensitization of
      functional responses may occur are considered and are divided into methodological
      and non-methodological factors. 4. Methodological factors discussed are: the
      concentration of agonist used for inducing desensitization and the washout times
      before construction of the post-incubation concentration-response curve (CRC),
      the need for correction of CRCs from time-matched controls, and the methods
      adopted for plotting CRCs. 5. Four non-methodological factors are considered.
      Firstly, the roles of different receptor reserves for the responses of each
      tissue can have an important effect on whether desensitization is apparent; a
      large reserve will make desensitization less likely to be apparent. Secondly,
      there is more than one site at which desensitization occurs; receptors are
      uncoupled from adenylyl cyclase activation, there is an additional site at the
      level of stimulation of cyclic AMP-dependent protein kinase and betaARs may
      ultimately be down-regulated. These processes may differ depending on the tissue
      and conditions and this may influence whether differential desensitization occurs
      between tissues. Thirdly, the apparent degree of desensitization after washout of
      an agonist can depend upon the rate of resensitization. Experiments to overcome
      this problem are described which demonstrate betaAR desensitization in the
      continued presence of agonist. Finally, the role of up-regulation of PDE in
      desensitization is discussed.

PMID- 10961740
TI  - Modification of cardiovascular responses to spinal GABA(B) receptor stimulation
      by cAMP and by K(ATP) channel blockade in anaesthetized rats.
AB  - 1. Intrathecal (i.t.) injection of baclofen (30, 60 and 100 nmol), a GABA(B)
      receptor agonist, produced a dose-dependent decrease in blood pressure (BP) and
      heart rate (HR). 2. Pretreatment with 5-aminovaleric acid (50 nmol), a GABA(B)
      receptor antagonist, blocked the depressor and bradycardic effects of baclofen
      (100 nmol). 3. Pretreatment with 8-bromo-cAMP (10 nmol), a cAMP analogue,
      attenuated the depressor and bradycardic effects of baclofen (100 nmol), but not
      with 8-bromo-cGMP (10 nmol), a cGMP analogue. 4. In addition, pretreatment with
      glipizide (20 nmol), an ATP-sensitive K+ channel (K(ATP)) blocker, attenuated the
      depressor and bradycardic effects of baclofen (100 nmol). These results suggest
      that GABA(B) receptors in the spinal cord have an inhibitory role in the central
      cardiovascular regulation and that these depressive and bradycardic actions are
      modified by cAMP and by K(ATP) channel blockade.

PMID- 10961741
TI  - Involvement of cAMP and beta-adrenoceptors in the relaxing effect elicited by
      flavonoids on rat uterine smooth muscle.
AB  - 1. The effect of the flavonoids genistein (3-100 microM), kaempferol (3-60
      microM) and quercetin (1-100 microM) on KCl (60 mM)-induced tonic contraction in
      rat smooth muscle was assayed. In the same way, the modification of these effects
      in the presence of an inhibitor of protein kinase (PKA) (Rp-cAMPS), an inhibitor
      of phosphodiesterase (papaverine) and beta-adrenoreceptor blocking agents
      (propranolol and atenolol) was studied. 2. The flavonoids totally relaxed the KCl
      induced tonic contraction (IC50: genistein 20.2 +/- 2.0 microM, n = 11;
      kaempferol 10.1 +/- 1.6 microM, n = 8; quercetin 13.2 +/- 1.2 microM, n = 8). 3.
      The incubation with Rp-cAMPS (10 and 100 microM) 30 min prior to KCl shifted the
      dose-response curve of the flavonoids to the right, increasing their IC50 up to
      27.8 +/- 3.8 and 31.9 +/- 7.3 microM, respectively, for genistein; 24.7 +/- 0.2
      and 19.6 +/- 4.9 microM, respectively, for kaempferol; 18.8 +/- 2.2 and 18.4 +/-
      1.5 microM, respectively, for quercetin. 4. Papaverine (3-100 microM) also
      relaxed the contraction induced by KCl and this effect was significantly
      displaced to the right with Rp-cAMPS (10 microM) (IC50 12.1 +/- 2.2 vs. 16.5 +/-
      3.1 microM). Papaverine (3 microM) added to the organ bath 15 min before the
      contractile agent increased the relaxing effect of the flavonoids and
      significantly decreased their IC50 (genistein 20.2 +/- 2.0 vs. 9.8 +/- 1.4
      microM; kaempferol 10.1 +/- 1.6 vs. 6.6 +/- 0.7 microM; quercetin 13.2 +/- 1.2
      vs. 7.8 +/- 1.4 microM). 5. The incubation with atenolol (10 microM) did not
      alter the relaxing effect of the flavonoids. In the same experimental conditions,
      propranolol (10 microM) did not modify the effect of genistein and kaempferol,
      but shifted the response curve of quercetin significantly to the right (13.2 +/-
      1.2 vs. 17.7 +/- 3.4 microM). 6. The results suggest that genistein, kaempferol
      and quercetin produced the relaxation of uterine smooth muscle by increasing
      intracellular cAMP. Beta-adrenoceptors could also be involved in the effect of
      quercetin.

PMID- 10961742
TI  - Pharmacological analysis of vasoconstrictor responses to periarterial purinergic
      nerve stimulation.
AB  - 1. Periarterial electrical nerve stimulation at a low frequency (1 Hz) readily
      induced a vasoconstrictor response of the canine splenic artery in a pulse number
      related manner (1-30 pulses of trains). The vasoconstrictor response to trains of
      up to 10 pulses at 1 Hz of stimulation appeared to be monophasic, whereas it
      became clearly distinguished into two phases at a longer train of 30 pulses. 2.
      The monophasic vasoconstrictor responses to trains of 1, 3 or 10 pulses were not
      modified by an alpha1-adrenoceptor blocking agent, prazosin (0.1 microM), but
      were completely inhibited by the P2X receptor desensitization with alpha,beta
      methylene adenosine 5'-triphosphate (alpha,beta-methylene ATP; 1 microM). The 1st
      phase of vasoconstriction induced by a train length of 30 pulses was not
      influenced by the treatment with prazosin, but was abolished by alpha,beta
      methylene ATP. The 2nd phase response was markedly inhibited by prazosin, and the
      remaining response of this phase was blocked by alpha,beta-methylene ATP. 3.
      Rauwolscine (0.3 microM), an alpha2-adrenoceptor antagonist, enhanced the
      vasoconstrictor responses to trains of 1, 3 or 10 pulses. Particularly at 10
      pulses of electrical stimulation, the vasoconstrictor responses were
      significantly potentiated. The blockade of neuronal uptake of noradrenaline with
      imipramine (1 microM) did not affect the vasoconstrictor responses to trains of
      1, 3 or 10 pulses. 4. It is concluded that short pulse trains of stimulation at a
      low frequency may selectively activate a purinergic component of sympathetic
      cotransmission, and the prejunctional alpha2-adrenergic feedback mechanism may
      tonically participate into the modulation of ATP release. Imipramine-sensitive
      neuronal uptake mechanism may not play an important role in regulating vascular
      responses to periarterial purinergic nerve stimulation.

PMID- 10961743
TI  - Sertraline inhibits the contractile responses to noradrenaline, KCl and
      electrical field stimulation of rat isolated vas deferens.
AB  - 1. The aim of this study was to investigate the effect of sertraline, a selective
      serotonin re-uptake inhibitor, on contractile responses to noradrenaline (NA),
      KCl, serotonin (5-HT) and electrical field stimulation of rat isolated vas
      deferens. 2. Pre-treatment with 10(-4) M sertraline showed inhibitory effects on
      responses to NA, KCl, 5-HT and electrical field stimulation, while pre-treatment
      with 10(-6) and 10(-5) M sertraline caused potentiation of responses to NA (10(
      7) and 10(-6) M). 3. A voltage-dependent calcium channel activator, Bay K 8644,
      restored the inhibited responses when sertraline was washed out of the organ
      bath, although restoration could not be seen when sertraline was not removed. 4.
      The inhibition of the contractile responses by sertraline pre-treatment may be
      via a mechanism through calcium channels which is additional to the selective
      serotonin re-uptake inhibitory effect of sertraline.

PMID- 10961745
TI  - Safety and success of early laparoscopic cholecystectomy for acute cholecystitis.
AB  - Although elective laparoscopic cholecystectomy is today's gold standard for the
      treatment of symptomatic cholelithiasis, its safety and effectiveness for acute
      cholecystitis remain controversial. The authors present a retrospective study
      comparing laparoscopic cholecystectomy in the acute versus the elective setting.
      A total of 605 patients were treated surgically for gallstone disease between
      August 1991 and January 1999. A total of 269 patients (44.5%) underwent surgery
      for acute cholecystitis as soon as possible after diagnosis, and elective
      cholecystectomy was performed on 336 patients (55.5%) for symptomatic gallstones.
      Initial open cholecystectomy was performed on 52 (19.3%) of the acute patients
      and 16 (4.8%) of the elective patients. Laparoscopic cholecystectomy was
      attempted on 217 of the acute patients (80.7%), with 11 cases (5.1%) converted to
      open cholecystectomy, and on 320 (95.2%) of the elective patients, with 6 cases
      (1.9%) converted to open cholecystectomy. The mean (+/-SD) operative time for the
      acute and elective patients was 105 (+/-38) and 85 (+/-21) minutes, respectively
      (P < 0.05). There was no perioperative mortality in either laparoscopic group.
      Surgical complications related to laparoscopic cholecystectomy in the acute and
      elective groups occurred in six (2.9%) and eight (2.5%) cases, respectively (P =
      NS). The current study shows that early laparoscopic cholecystectomy for acute
      cholecystitis is safe and efficient. Low conversion rates can be maintained with
      strict guidelines for appropriate patient selection, adequate experience, and
      proper laparoscopic technique.

PMID- 10961744
TI  - The prevention of bile duct injury during laparoscopic cholecystectomy from the
      point of view of anatomic variation.
AB  - The aim of this study was to evaluate ways to prevent bile duct injury during
      laparoscopic cholecystectomy in patients with anomalous biliary tract anatomy.
      The biliary tract was studied using cholangiograms of 511 patients who had
      gallbladder disease and was dissected in 92 cadaveric specimens. The authors
      classified confluent forms of the cystic duct and the bile duct into five
      different types, including four anomalous types. Sixteen instances (3.13%) of
      anatomic variation of the biliary tract were found among the patients, and four
      cases (4.35%) were found in the cadavers. Among the 511 patients, there were 495
      cases of type C anatomy, three cases of type A, seven cases of type R, six cases
      of type P, and zero cases of type L; among the 92 cadaveric specimens, there were
      88 cases of type C anatomy, one case of type R, two cases of type P, and one case
      of type L. For anatomic types A, P, and R, there is a high probability of risk of
      cutting the wrong duct. Therefore, it is important to clarify the anatomy of the
      biliary tract by preoperative examination and to carefully dissect the cystic
      duct close to the neck of the gallbladder during laparoscopic cholecystectomy.
      Anatomic variation of the biliary tract is common and can create a rare pitfall
      during laparoscopic cholecystectomy.

PMID- 10961746
TI  - Are liver cirrhosis and portal hypertension associated with an increased risk of
      bleeding during laparoscopy? A retrospective analysis of 1,000 consecutive cases.
AB  - Laparoscopy is a relatively safe invasive procedure. However, the rate of
      bleeding complications during this procedure is still debatable. Moreover, it is
      not clear whether portal hypertension may increase the risk of this event. The
      authors analyzed retrospectively the records of 1,000 consecutive patients with
      chronic liver disease undergoing laparoscopy and guided direct-vision hepatic
      biopsy, and they examined the rate of bleeding complications from the trocar site
      after insertion of the Veress needle or after liver biopsy. A total of 400 of
      1,000 patients had liver cirrhosis. Of these, 22.7% had splenomegaly, 13.0% had
      laparoscopic signs of portal hypertension, and 8.2% had esophageal varices.
      Bleeding occurred in 0.9% of patients from the trocar site, in 0.2% from the
      biopsy site, and in 0% from the Veress needle site. These figures were
      independent of the presence of advanced liver disease, with or without portal
      hypertension. Bleeding complications occur rarely during laparoscopy with guided
      liver biopsy and do not seem to be related per se to the presence of liver
      cirrhosis and portal hypertension. If anything, bleeding complications represent
      an unpredictable event in most cases.

PMID- 10961747
TI  - Technical modifications for laparoscopic appendetomy and other pelvic procedures
      using microinstruments.
AB  - Reusable microinstruments are used in a modification of the three-port technique
      for laparoscopic appendectomy and other pelvic procedures; the method is
      described herein. Fifty-seven consecutive patients were operated upon using this
      technique. There was no mortality; there were two minor complications and no
      conversions to laparotomy. Pain medication needs were minimal in all patients,
      and the cosmetic results were excellent. The use of microinstruments for pelvic
      laparoscopic procedures is safe and cost-effective using the technical
      modifications described.

PMID- 10961748
TI  - Prospective randomized trial comparing bowel cleaning preparations for
      colonoscopy.
AB  - Colonoscopy is commonly accepted as the procedure of choice for the detection and
      treatment of colonic lesions. The current study was undertaken to compare
      effectiveness and tolerance of different bowel preparations. Three hundred
      patients were randomized into three groups, to be administered either a senna
      compound, a polyethylene glycol lavage, or an oral sodium phosphate (NaP)
      solution. Tolerance of the preparation was considered. After each colonoscopy,
      the endoscopist blindly scored cleansing for each bowel segment and defined the
      quality of the examination as "optimal," "acceptable," or to be repeated.
      Significantly more patients in Group C (68%) achieved a "good" cleansing compared
      with Group B (50%; P < 0.0001) and with Group A (38%; P < 0.005). Sixty-three
      percent of constipated patients obtained a "good" preparation in Group C, which
      was significantly higher than in Group A (28%; P < 0.05) and than in Group B
      (42%; P < 0.02). Feasibility of the examination was considered "optimal" in 80%
      of procedures in Group C, which was higher than in Group A (59%; P < 0.005) and
      in Group B (62%; P < 0.005). The tolerance of preparation was "good" in 93% of
      the examinations for Group C. This prospective randomized trial showed good
      effectiveness of NaP solutions, with an optimal tolerance. Results of use of the
      NaP solution showed a clear advantage for constipated patients, with similar
      results for nonconstipated patients. The author believes that the NaP solution
      should be the standard preparation for elective colonoscopy.

PMID- 10961749
TI  - Laparoscopic placement of the Tenckhoff catheter for peritoneal dialysis.
AB  - Continuous ambulatory peritoneal dialysis catheters can be inserted by open
      laparotomy as well as by laparoscopy. A prospective randomized study was
      scheduled to investigate the results of the laparoscopic versus open laparotomy
      technique for placement of continuous ambulatory peritoneal dialysis catheters.
      Fifty patients were enrolled and randomly allocated into two groups of 25
      patients each. Group A underwent continuous ambulatory peritoneal dialysis
      catheter placement via the open laparotomy technique. In 22 patients, catheters
      were inserted via midline incision, and in 3 patients with histories of previous
      catheterization, a paramedian incision was used. Continuous ambulatory peritoneal
      dialysis was started 24 to 48 hours later. Group B underwent laparoscopic
      placement of the catheter with fixation into the pelvis and suture closure of the
      port wounds. In 21 patients, this catheter placement was the first such
      placement, and in 4 patients, a previous catheter had been inserted by the open
      technique and removed for dysfunction. Continuous ambulatory peritoneal dialysis
      was started at the end of the procedure. The mean operative time was 22 minutes
      in group A and 29 minutes in group B (P < 0.001). Fluid leakage was observed in
      eight patients in group A, but in no patients in group B (P < 0.005). Peritonitis
      occurred in five patients in group A and in three patients in group B (P > 0.1).
      Tip migration occurred in five patients in group A and no patients in group B (P
      < 0.005). In group B, two patients underwent a simultaneous cholecystectomy and
      one underwent incisional hernia repair. Laparoscopic placement of a Tenckhoff
      catheter leads to better function than does the open procedure; it allows
      immediate start of dialysis without fluid leakage and permits simultaneous
      performance of other laparoscopic procedures.

PMID- 10961750
TI  - Thoracoscopic resection as the preferred approach to posterior mediastinal
      neurogenic tumors.
AB  - Traditionally, resection of posterior mediastinal neurogenic tumors (PMNTs) has
      been through a posterolateral thoracotomy. Although thoracoscopic resection of
      these tumors has been advocated, treatment guidelines have not been reported
      previously. The authors report a thoracoscopic resection of a PMNT and conducted
      a retrospective review of similar cases in the literature. Successful
      thoracoscopic resection was compared with tumor size and type using a nonpaired t
      test (alpha: P < 0.05). A total of 29 patients (13 men, 16 women), aged 26 to 68
      years, who underwent a thoracoscopic resection of a PMNT were identified.
      Preoperative imaging included chest radiography and computed tomography in all
      patients and magnetic resonance imaging in 15 of 29 patients (52%). All tumors
      were located in the posterior mediastinum without preoperative evidence of
      invasion or malignancy. Conversion to an open procedure was necessitated in 12 of
      29 (41%) patients ("minithoracotomy" in 11, posterolateral thoracotomy in 1).
      Tumor size necessitating conversion to an open procedure (mean = 4.79 cm) and
      tumor size amenable to thoracoscopy alone (mean = 3.84 cm) were not significantly
      different (P < 0.09). Pathology revealed 22 schwannomas (76%), 6 ganglioneuromas
      (21%), and 1 malignant schwannoma (3%) and was not associated with conversion to
      an open procedure (P < 0.99). Thoracoscopic resection of PMNTs can be performed
      successfully, regardless of tumor type or size; however, malignancy, local
      invasion, and tumors >5 cm may require an open procedure. Thoracoscopic resection
      can replace thoracotomy in the treatment of PMNTs.

PMID- 10961752
TI  - In vitro evaluation of the accuracy of open-configuration MRI in endovascular
      techniques.
AB  - The purpose of this study was to determine the accuracy of an interventional
      magnetic resonance imaging (iMRI) system to position an endovascular catheter in
      an in vitro model that simulated an infrarenal aortic aneurysm. Adequate
      visualization of abdominal aortic aneurysms (AAAs) was shown previously in
      humans. A dedicated near-real-time imaging protocol readily available on a Signa
      SP 0.5T open configuration MRI unit (General Electric Medical Systems, Milwaukee,
      WI, USA) was used to image the AAAs of ten human volunteers. A pulsatile in vitro
      model that simulated an AAA was built, which included the kidneys, the renal
      arteries, the aorta, and the iliac arteries. A catheter was advanced to a
      predetermined target through one of the iliac limbs of the model. Using two
      different techniques, the accuracy with which an interventionist could position
      the endovascular catheter under the near-real-time guidance of the iMRI system
      was evaluated. The AAAs of all ten patients were visualized, including the
      aneurysm wall, the thrombus within it, and the residual lumen, while maintaining
      adequate contrast, signal, and imaging speed. The position of the catheter was
      evaluated on target in 42 in vitro procedures. This series of tests showed an
      average accuracy of 1 mm for catheter positioning. The near-real-time imaging
      mode of the iMRI system enabled satisfactory evaluation of human AAAs, and it
      showed great accuracy for catheter positioning in the in vitro model. These
      results provide optimism regarding the potential of iMRI in endovascular surgery.

PMID- 10961751
TI  - Video-assisted transthoracic sympathectomy in the treatment of primary
      hyperhidrosis: friend or foe?
AB  - The authors hypothesize that palmar hyperhidrosis is a systemic manifestation of
      abnormal sudomotor function; consequently, thoracoscopic sympathectomy to
      alleviate symptoms in the hands may result in heat dissipation because sweating
      is transferred to other sites. To investigate this phenomenon and to determine
      whether it adversely affects patient satisfaction, a standard questionnaire was
      administered to 626 patients who underwent sympathectomy at a university
      associated public hospital between 1991 and 1998; only patients treated at least
      6 months before questionnaire distribution were included in the study. Replies
      were received from 336 (53.7%) individuals. The surveyed patients underwent
      bilateral T2, T3 (palmar sweating), or T3, T4 (axillary sweating) sympathectomy
      by a standard video-assisted transthoracic technique. Main outcome measures
      included the incidence of dry hands, compensatory sweating, chest pain, upper
      limb muscle weakness, shortness of breath, and gustatory phenomena; in addition,
      patient perception of the success of the surgical procedure was assessed. After
      sympathectomy, 97.3% (P < 0.0001) and 29.2% (P < 0.001) of patients reported
      significant improvement in palmar hyperhidrosis and axillary sweating,
      respectively. Postsurgery, severe compensatory sweating was experienced in 90% of
      patients (P < 0.0001). The sites of compensatory sweating were the back (75%),
      abdomen (51%), feet (23%), groin and thigh (13%), chest (13%), and axillae (8%).
      Transient whole-body sweating for no apparent reason was experienced in 30% of
      patients. Thirty-seven patients (11%) regretted having undergone the surgical
      procedure. In contrast, 25% and 64% of patients were either satisfied or very
      satisfied with the outcome of the procedure. From the survey results, the authors
      conclude that palmar hyperhidrosis is a systemic manifestation of abnormal
      sudomotor function and that thoracic sympathectomy may alleviate symptoms in a
      large proportion of patients. However, for some individuals, compensatory
      sweating may prove to be an equally troublesome handicap. Because the occurrence
      of severe compensatory sweating is unpredictable, a reversible sympathectomy may
      be desirable.

PMID- 10961753
TI  - Laparoscopic esophagomyotomy with dor anterior fundoplication in a child with
      achalasia.
AB  - Laparoscopic myotomy with anterior fundoplication was successfully performed on a
      12-year-old boy with esophageal achalasia. After completion of a longitudinal
      esophagocardiomyotomy approximately 6 cm in length, a 180 degrees fundic patch
      was sutured anteriorly to the myotomized esophagus according to the Dor-Gavriliu
      technique. The patient showed a rapid and uneventful recovery with complete
      resolution of his preoperative symptoms. The nonobstructive antireflux procedure
      can be safely performed concomitantly with another surgery, even in a pediatric
      patient.

PMID- 10961754
TI  - Gastrointestinal stromal tumor of the stomach successfully treated by
      laparoscopic proximal gastrectomy with jejunal interposition.
AB  - The authors describe a patient with a bleeding gastrointestinal stromal tumor of
      the stomach who was treated successfully by laparoscopic proximal gastrectomy
      with jejunal interposition. Immunohistochemically, the tumor was positive for
      vimentin and CD34 and was diagnosed as a gastrointestinal stromal tumor of low
      grade malignancy. Because it is difficult to diagnose this disease preoperatively
      and a malignant phenotype has been reported, resulting in liver metastasis and
      peritoneal dissemination, it is desirable to treat this disease with as little
      manipulation as possible. To achieve this, laparoscopic surgery is a feasible
      option for the treatment of gastrointestinal stromal tumors.

PMID- 10961755
TI  - Laparosopic removal of large gastric phytobezoars.
AB  - Large gastric bezoars are difficult to remove endoscopically. A 78-year-old man
      presenting with abdominal pain and loss of appetite for 4 months was admitted and
      evaluated. Gastroscopy disclosed two large phytobezoars within the stomach.
      Laparoscopic removal was undertaken. The bezoars were removed via a gastrotomy
      using the three-trocar technique. They were successfully retrieved from the
      abdominal cavity using an improvised "endobag" made from a simple surgical glove.
      Such an endobag presents several advantages; they are easy to make, sterile,
      economical, readily available, disposable, there is ample space to manipulate the
      specimen within, and there is minimal risk of contamination throughout the
      procedure. The authors recommend this approach for the treatment of patients with
      large gastric bezoars in whom laparotomy is indicated.

PMID- 10961756
TI  - Endoscopic band ligation for gastric ulcer bleeding.
AB  - Endoscopic band ligation is used commonly to treat variceal bleeding. The use of
      band ligation has been described in selected cases of nonvariceal bleeding. The
      successful use of endoscopic band ligation, after the failure of standard
      techniques, to arrest bleeding in two cases of gastric ulcer hemorrhage is
      reported. Prospective studies are indicated to further evaluate this technique.

PMID- 10961757
TI  - The difficult gallbladder: technical tips for laparoscopic cholecystectomy.
AB  - Conversion of laparoscopic cholecystectomy to laparotomy may increase
      postoperative complications and convalescence and should therefore be avoided
      when possible. The authors present three technical tips that may prevent
      unnecessary conversion to open procedure (suspension sutures in the gallbladder,
      use of the Endo Paddle Retract (United States Surgical Corp., Norwalk, CT, USA)
      to depress abdominal viscera, and subtotal cholecystectomy). These methods may be
      used in situations in which there is no operative risk for complications, such as
      bile duct injury, but technical aspects of the operation normally would have
      resulted in conversion to laparotomy.

PMID- 10961758
TI  - Unintentional ileostomy: a complication of the videolaparoscopic method? Report
      of the first case.
AB  - Jejunostomy is widely acknowledged in the literature as a means for enteral
      nutrition. Complication rates range from 16% to 46% for the classical open
      technique and from 11% to 70% for the several mini-invasive techniques currently
      in use, including the laparoscopic techniques. The most probable complications
      are abscess, intestinal obstruction, abdominal wall infection, intraperitoneal
      leakage, enterocutaneous fistula, and loss, elbowing, or even rupture of the
      enteral probe. The authors report the case of a patient with severe malnutrition
      concomitant with advanced gastric cancer who underwent jejunostomy because of an
      incapacity for normal oral feeding. Previous attempts to pass a nasal enteral
      probe were not successful, even with the aid of endoscopy. Videolaparoscopy was
      indicated for adequate staging of the neoplasm and for performance of video
      assisted jejunostomy. During the procedure, an extensive carcinomatous process
      was observed that rendered comprehension of the abdominal anatomy extremely
      difficult. Consequently, while attempting jejunal catheterization, unintentional
      catheterization of the terminal ileum took place. The authors discuss this first
      reported case of unintentional ileostomy and review the literature.

PMID- 10961759
TI  - Inexpensive retraction technique for advanced laparoscopic procedures.
AB  - The described technique offers surgeons an inexpensive simple way to hold
      intraperitoneal structures in position for long periods with minimal trauma.

PMID- 10961760
TI  - Liberal use of a bag made from a surgical glove during laparoscopic surgery for
      specimens retrieval.
AB  - Laparoscopic surgery has been gaining wide acceptance in recent years. Tissue
      removal from the abdominal cavity becomes a paramount issue, especially when the
      specimen is infected, contains several fragments, or potentially contains a
      malignancy. Several sophisticated instruments and devices have been designed for
      this purpose. However, most of these are expensive, difficult to handle, and come
      in a fixed size. Condoms, glove fingers, and zipper-type plastic bags have been
      tried also, but with limited success. The authors report use of a simple bag made
      from a surgical glove to collect specimens; a long purse-string suture surrounds
      the opening or the base of the glove finger to secure material during retrieval.
      This method has been found to be simple and convenient, and necessary
      construction material is readily available. The bag not only protects the
      specimen from contact with the wound but also cuts short the operating time. The
      technique and advantages are described.

PMID- 10961761
TI  - Isolated thrombosis of the external jugular vein.
AB  - Thrombosis of the external jugular vein (EJV) is an infrequent clinical condition
      that has been associated with central venous catheterization, head and neck
      infections, intravenous drug abuse, and compression at the affected site. The
      authors report a case of thrombotic obstruction of the EJV in the late
      postoperative period after laparoscopic anterior lumbar interbody fusion. A 40
      year-old morbidly obese woman with a depressive syndrome was diagnosed with L5-S1
      discopathy and was submitted to laparoscopic anterior isthmic fusion. The
      operation lasted approximately 6 hours, during which the patient remained in a
      supine decubitus and Trendelenburg position. The left radial artery, peripheral
      veins, and right internal jugular vein were canalized. The internal jugular vein
      catheter was electively withdrawn 24 hours after the intervention. The
      postoperative period was satisfactory, and the patient was started on prophylaxis
      with low-molecular-weight heparin. She sat up and began walking at 24 hours and
      was discharged to her home 4 days after the procedure. Eight days after discharge
      she returned, experiencing right cervical pain. Palpation revealed a painful
      induration and erythematous area under the anterior edge of the
      sternocleidomastoid muscle. Results of otoscopy and laryngoscopy were normal.
      Cervical echo-Doppler disclosed an image consistent with EJV thrombosis. The most
      frequent causes of jugular vein thrombosis are mentioned above. A higher
      incidence has been described after upper abdomen and pelvic surgery; other
      contributing factors are age, obesity, and associated illness. There are few
      references in the literature to position-induced EJV thrombosis in the late
      postoperative period. The authors' patient presented signs and symptoms of EJV
      thrombosis (probably because of various factors), which was confirmed by echo
      Doppler study and treated with 10 days of calcic heparin.

PMID- 10961762
TI  - Visual contrast gain control in migraine: measures of visual cortical
      excitability and inhibition.
AB  - The present study examined the extent to which migraineurs demonstrate interictal
      visual cortical hyperexcitability as a result of poor inhibitory control in the
      visual system. We employed a well-established psychophysical measure of
      inhibition, visual contrast gain control. The task involved detecting a briefly
      presented target that was superimposed on a highly excitable high contrast
      masking pattern. The strength of inhibition was assessed by comparing target
      detection thresholds with and without the operation of gain controls. Migraineurs
      with and without aura (n=25, n=22, respectively) were compared with those with no
      history of migraine (n=25). Our results do not indicate a loss of inhibition in
      migraine; the strength of inhibitory feedback contrast gain controls was similar
      between migraineurs and controls. We did however, find a statistically greater
      masking effect in migraineurs compared with controls in the zero delay condition,
      suggesting cortical hyperexcitability in migraine. Possible mechanisms of
      cortical hyperexcitability are discussed in light of the results.

PMID- 10961763
TI  - The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks
      in cluster headache.
AB  - The administration of nitroderivatives in cluster headache (CH) sufferers is the
      most reproducible experimental paradigm to induce spontaneous-like pain attacks.
      Previous uncontrolled studies have reported that the local use of anaesthetic
      agents in the area of the sphenopalatine fossa is able to extinguish
      nitroglycerin (NTG)-induced pain in CH. The present study, carried out according
      to a double-blind placebo-controlled design, included 15 CH patients, six with
      episodic CH (mean +/- SD age of 36.8+/-5.6 years), and nine with chronic CH
      (37.8+/-10.4 years). Patients had undergone a standard NTG test (0.9 mg
      sublingually), during which the intensity of pain was scored using a
      visuoanalogic scale (VAS, range 0-10). Nine patients (two with the episodic form,
      seven with the chronic form) experienced a typical, spontaneous-like attack on
      the usual side, occurring in all cases within 45 min. In these patients, the test
      was repeated with an interval of 2 days, and once pain intensity reached 5 on the
      VAS, a 10% solution of cocaine hydrochloride (1 ml, mean amount per application
      40-50 mg), or 10% lidocaine (1 ml), or saline was applied using a cotton swab in
      the area corresponding to the sphenopalatine fossa, under anterior rhinoscopy.
      This was done in both the symptomatic and the non-symptomatic side, for 5 min.
      Treatments were always performed randomly, in separate sessions. All patients
      responded promptly to both anaesthetic agents, with complete cessation of induced
      pain occurring after 31.3+/-13.1 min for cocaine and 37.0+/-7.8 min for lidocaine
      (M+/-SD). In the case of saline application, pain severity increased thereafter,
      and extinction of the provoked attacks occurred with a latency of 59.3+/-12.3 min
      (P<0.01 and P<0.01 vs. cocaine and lidocaine, respectively, Mann-Whitney U-test).
      While further suggesting that the sphenopalatine ganglion participates in the
      mechanisms of pain, these findings indicate that the local administration of the
      anaesthetic agents cocaine and lidocaine is effective on NTG-induced CH attacks,
      and may be used in the symptomatic treatment of this disorder.

PMID- 10961764
TI  - SB-220453, a potential novel antimigraine agent, inhibits nitric oxide release
      following induction of cortical spreading depression in the anaesthetized cat.
AB  - Profound nitric oxide release associated with cortical spreading depression (SD),
      has been implicated in stroke, traumatic brain injury and migraine
      pathophysiology. SB-220453 represents a mechanistically novel, well-tolerated
      class of compounds which may have therapeutic potential in the treatment of
      conditions associated with neuronal hyperexcitability and inflammation. The aim
      of the present study was to investigate the effects of SB-220453 on the nitric
      oxide (NO) release associated with SD in the anaesthetized cat. In vehicle
      treated animals, KCl application for 6 min to the cortical suface produced
      repeated changes in extracellular direct current field potential with associated
      NO release. This activity was sustained for a median duration of 55 min (25-75%
      range, 32-59 min) and 59 min (25-75% range, 34-59 min), respectively. SB-220453
      (1, 3 and 10 mg/kg i.p.) produced a dose-related inhibition of this activity and
      at the highest dose tested, the median duration of changes in extracellular field
      potential and NO release were reduced to 4 min (25-75% range, 4-5 min) and 5 min
      (25-75% range, 5-5 min), respectively. No effect was observed on basal systemic
      haemodynamic parameters or resting cerebral laser Doppler blood flux at any of
      the doses of SB-220453 tested. SB-220453 therefore represents a novel compound to
      assess the potential benefit of inhibiting SD associated nitric oxide release in
      neurological disease.

PMID- 10961765
TI  - Linked activation of nitric oxide synthase and cyclooxygenase in peripheral
      monocytes of asymptomatic migraine without aura patients.
AB  - Many reports indicate that nitric oxide (NO) could be involved in migraine
      without aura (MWA), an extremely diffuse clinical event. Since monocyte may be a
      relevant source of NO, we analysed monocyte activation in MWA patients, in a
      period in which they were free of symptoms. NO basal production by MWA peripheral
      monocytes was significantly higher than in healthy subjects (91.25+/-8.6
      microM/10(6) cells vs. 22.6+/-3.2 microM/106 cells). Interestingly, even the
      release of prostaglandin E2 (PGE2), was higher in MWA patients than in healthy
      subjects (3137+/-320 pg/10(6) cells vs. 1531+/-220 pg/10(6) cells). The
      incubation of monocytes from healthy subjects and MWA patients with N-nitro-L
      arginine methyl ester caused a marked decrease of both NO and PGE2 release. We
      hypothesise that NOS and cyclooxygenase pathways in monocytes are linked and are,
      in MWA patients, up-regulated, even in a symptoms-free period. NO and PGE2
      hyperproduction could therefore be involved in the neurovascular modifications
      leading to migraine attacks.

PMID- 10961766
TI  - Prednisone as initial treatment of analgesic-induced daily headache.
AB  - The majority of the patients who seek medical care in tertiary headache centres
      present with transformed migraine, and convert to daily headache, as a result of
      excessive intake of symptomatic medications (SM). This study aimed to analyse the
      possibility of using a short course of oral prednisone for detoxifying patients
      with chronic daily headache due to medication overuse in an out-patient setting.
      Four hundred patients with headache occurring more than 28 days per month for
      longer than 6 months were studied (mean baseline frequency of 0.96). Symptomatic
      medications were stopped suddenly and prednisone was initiated in tapering doses
      during 6 days, followed by the introduction of preventive treatment. Withdrawal
      symptoms and the frequency, intensity and duration of the headache, as well as
      the consumption of rescue medications, were analysed during the first 16 and 30
      days of withdrawal. Eighty-five percent of the patients experienced a reduction
      in headache frequency and no patients presented severe attacks during the first 6
      days. With regard to the following 10 days, 46% of the patients experienced at
      least 2 days without headache and 58% less intense attacks. Most of the patients
      noticed attacks with longer duration. After the 30-day period there was a
      significant decrease in headache frequency (mean 0.83, P<0.001), and no patients
      returned to overuse of SM. This study demonstrates that it is possible to
      detoxify patients suffering from rebound headaches, using oral prednisone during
      the first days of withdrawal, in an out-patient setting.

PMID- 10961767
TI  - Intracisternal octreotide does not ameliorate orthodromic trigeminovascular
      nociception.
AB  - Octreotide is a long-acting somatostatin analogue that has been effectively used
      to treat migraine. Octreotide poorly penetrates the blood-brain barrier, but has
      potential central target sites in the trigeminal nucleus caudalis, which is the
      primary central relay station for trigeminal nociceptive information in the
      brain. We studied the effect of intracisternally applied octreotide in a model of
      trigeminovascular stimulation in the unrestrained rat using intracisternal
      capsaicin infusion to stimulate intracranial trigeminal nerves. Fos expression in
      the outer layers of the trigeminal nucleus caudalis (TNC I-II) and behavioural
      analysis were used to measure the effects of octreotide on capsaicin-induced
      trigeminovascular activation. Increases of head grooming and scratching behaviour
      are an indication of octreotide-induced trigeminal activation. However,
      octreotide did not alter the average capsaicin-induced Fos expression in the TNC
      I-II and capsaicin sensitive behaviours were not modified by octreotide
      pretreatment. This argues against a role for central (TNC I-II) somatostatin
      receptors in the processing of the nociceptive trigeminovascular signals.

PMID- 10961769
TI  - Extratrigeminal short-lasting unilateral neuralgiform headache with conjunctival
      injection and tearing (SUNCT): new pathophysiologic entity or variation on a
      theme?

PMID- 10961768
TI  - Prevention of migraine during prodrome with naratriptan.
AB  - OBJECTIVE: To determine the role of naratriptan in preventing migraine headache
      when administered during prodrome. PROCEDURES: Baseline phase: patients recorded
      prodrome symptoms and time of onset, time when patient knew that headache was
      inevitable, time of onset and severity of headache. Treatment phase: patients
      given naratriptan 2.5 mg to take at the time they knew headache was inevitable.
      Patients recorded prodrome symptoms and time of onset, time they knew headache
      was inevitable, time naratriptan administered, time of onset and severity of any
      headache. Patients treated three prodromes separated by at least 48 h. FINDINGS:
      Twenty patients completed both phases. During baseline phase, 59 prodromes were
      reported and all were followed by headache. Severity of headache: 5% mild, 51%
      moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of
      these, 38/63 (60%) were not followed by headache. Among headaches that occurred,
      the majority occurred within 2 h of naratriptan administration, suggesting that
      naratriptan is more effective in preventing headache if taken early in prodrome.
      Severity of 25 headaches: 44% mild, 24% moderate, 32% severe. CONCLUSIONS:
      Naratriptan 2.5 mg appears to prevent migraine headache when given early in
      prodrome. If headache occurs, severity appears to be reduced.

PMID- 10961770
TI  - Hemicrania continua responsive to rofecoxib.

PMID- 10961771
TI  - Recurrent thunderclap headache associated with reversible intracerebral vasospasm
      causing stroke.

PMID- 10961772
TI  - The role of adhesion molecules in migraine: a debate.

PMID- 10961774
TI  - The facts about getting into an orthodontic program.

PMID- 10961773
TI  - Sumatriptan nasal spray in the acute treatment of migraine: a review of clinical
      studies.

PMID- 10961775
TI  - RE: the form of the human arch.

PMID- 10961776
TI  - Incisor root resorptions due to ectopic maxillary canines imaged by computerized
      tomography: a comparative study in extracted teeth.
AB  - The purpose of the study was to analyze the ability of computerized tomography
      (CT) scanning to discriminate maxillary incisor root resorptions caused by
      ectopically erupting canines. Seventeen maxillary incisors were radiographed in
      vivo by CT scanning. Contiguous transverse CT scans with a slice thickness of 2
      mm were exposed perpendicular to the long axis of the lateral incisors and
      through the crown of the adjacent, ectopically positioned maxillary canine. Each
      scan was analyzed and the resorptions on the roots of the laterals were graded
      according to the maximum depth of the cavity. After the lateral incisors were
      extracted they were clinically inspected, photographed in different light
      settings and views, and probed at the contact area between the laterals and the
      canines. The assessment of the extent of resorption in 4 stages on the CT images
      compared with the in vitro observations of the extracted roots showed a high
      degree of agreement for the extent of loss of root substance for all teeth. We
      conclude that CT scanning performed with good technique accurately reveals tooth
      root resorption. The presence and influence of the inherent artifacts of tooth
      root resorption on CT scans are discussed.

PMID- 10961777
TI  - A cineradiographic study of deglutitive tongue movement and nasopharyngeal
      closure in patients with anterior open bite.
AB  - The purpose of this study was to investigate the movement of the tip and the
      dorsal surface of the tongue during deglutition in patients with anterior open
      bite using cineradiography. The subjects were 10 female patients with anterior
      open bites and 10 female controls with normal overbites. By cineradiography we
      established 7 stages of tongue movement and bolus position during deglutition and
      analyzed the tongue position, tongue movement and the time. The tongue-tip
      position was more protrusive during deglutition in anterior open bite than in the
      controls. After the head of the bolus arrived at the opening of the esophagus,
      the rear part of the dorsal surface of the tongue demonstrated slower movement in
      patients with anterior open bite than in controls. The nasopharynx closed earlier
      in patients with anterior open bite than in controls. It is suggested that
      anterior open bite patients had compensatory coordination of tongue movement,
      soft palate movement and pharyngeal constrictor muscle activity during
      deglutition.

PMID- 10961778
TI  - Prevalence of tooth transposition, third molar agenesis, and maxillary canine
      impaction in individuals with Down syndrome.
AB  - Alterations in the size, morphology and number of teeth are among the many
      inherited disorders that have been reported in individuals with Down syndrome. By
      contrast, third molar agenesis and tooth transposition have been largely ignored
      and the prevalence of canine impaction has not been reported. The intention of
      this study was to quantify the occurrence of these anomalies in a group of
      individuals with Down syndrome, using standardized records, which included a
      clinical examination, dental casts, and a panoramic radiograph. The results show
      a notably high prevalence of third molar agenesis (74% of individuals older than
      14 years), canine impaction (15%), and maxillary canine/first premolar
      transposition (15%), compared to published figures from random population
      samples. These anomalies should not be seen as separate, independent entities,
      but as associated phenomena. The slow rate of cell growth and a consequent
      reduced cell number that characterize this syndrome may be responsible for the
      underdevelopment of the upper jaw, the delayed dental development, the reduction
      in teeth number and size, and the altered path of canine eruption. No
      explanation, other than genetics, is immediately available to explain why the
      maxillary canine/first premolar transposition should represent another phenotypic
      expression of this trisomy.

PMID- 10961779
TI  - Maxillary arch size and shape in American blacks and whites.
AB  - American blacks have larger teeth than whites, but they less frequently exhibit
      crowding--apparently because of larger arch dimensions. This study quantified
      differences in arch size and shape in these 2 constituents of the US population.
      Eighteen dental and bony landmarks were digitized from the maxilla of each of 332
      subjects with permanent, intact dentitions, proportionately divided between
      blacks and whites, men and women. Linear, angular, and area measurements were
      computer-generated. Arch widths averaged 10% greater in blacks than whites, and
      mesiodistal arch depths had a greater difference, at 12%. Blacks, with a more
      square palate and significantly larger palatal index, were distinguished from
      whites primarily by greater intercanine and interpremolar widths. Arch perimeter
      was greater in blacks by 8%, and cross-sectional area of the arch was 19% greater
      in blacks than whites, so blacks and whites differ substantially for these
      parameters not only in size, but in shape as well. These differences are relevant
      in prosthodontics and orthodontics since individualization of treatment leads to
      more effective treatment by working within the patient's natural arch form
      instead of making patients fit a single standard.

PMID- 10961780
TI  - Mesiodistal crown dimensions and tooth size discrepancy of the permanent
      dentition of Dominican Americans.
AB  - The purpose of the study was to establish normative data on the mesiodistal crown
      dimensions of Americans of Dominican background. The Bolton tooth size analysis
      was performed on a sample of 54 Dominican Americans. The mean, range and standard
      deviation were calculated for the size of the teeth, and a coefficient of
      variation was obtained for the tooth size ratio. A 2-sample t-test was used to
      test for the statistical difference between means. In general, the values
      obtained for the Dominican American sample closely resembled previous data
      available for the African American population. The tooth size ratios obtained
      were compared to the Bolton ratios. The overall ratio was found to be 91.3,
      equivalent to the Bolton overall ratio, whereas the anterior ratio was 78.1,
      larger than the 77.1 Bolton ratio. The frequency of tooth size discrepancy
      outside 2 standard deviations from the Bolton mean was also calculated. An
      overall tooth size discrepancy was found in 11% of our sample, and 28% of the
      sample presented an anterior tooth size discrepancy.

PMID- 10961781
TI  - A comparison of shear-peel band strengths of 5 orthodontic cements.
AB  - The objective of this study was to compare the shear-peel band strength of 5
      orthodontic cements using both factory and in-office micro-etched bands. The 5
      orthodontic cements evaluated were a zinc phosphate (Fleck's Cement), 2 resin
      modified glass ionomer cements (RMGI)(3M Multicure glass ionomer and Optiband),
      and 2 polyacid-modified composite resin cements (PMCR)(Transbond Plus and Ultra
      Band Lok). Salivary contamination was examined with a polyacid-modified composite
      resin (Transbond Plus). Two hundred and eighty extracted human molar teeth were
      embedded in resin blocks and each was randomly assigned to the following 7
      groups: 6 groups with factory etched bands, 5 cement groups and salivary
      contaminated group, and 1 in-office micro-etched group. The cemented teeth were
      put in deionized water at 37 degrees C for 30 days and thermocycled for 24 hours.
      The force required to break the cement bond was used as a measure of shear-peel
      band retention. With the use of an Instron testing machine, a shear-peel load was
      applied to each cemented band. Data were analyzed with a one-way analysis of
      variance (ANOVA) with a Tukey test for the multiple comparisons. The RMGIs and
      PMCRs demonstrated significantly greater shear-peel band strengths compared to
      the zinc phosphate cement. No statistically significant differences were noted
      between the RMGI cement and PMCR cements and within the RMGI groups, however,
      there was a statistically significant difference within the PMCR groups.
      Significantly lower band strengths were noted with the saliva contaminated PMCR
      cement group (Transbond Plus) and the inpractice sandblasted PMCR group. Both
      RMGIs and PMCRs were found to demonstrate favorable banding qualities. The lower
      band strength with saliva-contaminated bands suggests that moisture control is
      critical when using a PMCR. The variability noted in the in-office micro-etched
      bands might be technique related.

PMID- 10961782
TI  - Orthopedic cervical headgear with an expanded inner bow in class II correction.
AB  - Forty consecutively referred children, 20 boys and 20 girls, with a Class II
      division I malocclusion and protrusive maxilla were treated with orthopedic
      cervical headgear with a 10 mm expanded inner bow and a long outer bow bent 15
      degrees upwards. The mean age of the children at the beginning of treatment was
      9.3 years (SD 1.3, range 6.6 to 12.4 years), and the average treatment time was
      1.8 years (SD 0.6, range 0.8 to 3.1 years). In all patients Class II molar
      relationships were successfully corrected to Class I molar relationships. This
      was accompanied by a marked widening of both maxillary and mandibular dental
      arches. The cephalometric analysis suggested that the observed improvement of the
      occlusion was due to an inhibition of forward growth of the maxilla and anterior
      downward rotation of the palate.

PMID- 10961783
TI  - Long-term changes in dentoskeletal pattern in a case with Beckwith-Wiedemann
      syndrome following tongue reduction and orthodontic treatment.
AB  - Long-term changes in the dentoskeletal pattern in a 6-year-old Japanese girl with
      Beckwith-Wiedemann syndrome were demonstrated. The patient showed macroglossia,
      which is the most common symptom of the syndrome, protruded lower lip, mandibular
      protrusion and anterior open bite. The jaw base relationship improved to skeletal
      Class I and the molar relationship to Angle Class I at the early preadolescent
      period following tongue reduction and phase I orthodontic treatment using a chin
      cap and tongue crib. Optimum intercuspation of teeth was achieved after edgewise
      treatment without orthognathic surgery, and a skeletal Class I apical base
      relationship and good facial profile were maintained after the retention period
      of 2 years. This case report suggests that early orthodontic treatment with
      tongue reduction can be effective in a case with Beckwith-Wiedemann syndrome to
      improve an abnormal dentoskeletal pattern.

PMID- 10961784
TI  - Class II correction with the modified sagittal appliance and maxillary second
      molar extraction.
AB  - The aim of this article is to describe the clinical use of the removable sagittal
      appliance combined with the use of a J-hook headgear. This technique was used to
      distalize the buccal segments following maxillary second molar extraction in the
      treatment of a Class II patient with labially positioned maxillary canines. The
      sagittal appliance was used full-time and the headgear was worn 10 to 12 hours
      per day. This proved to be an effective method for distalizing the maxillary
      buccal teeth without flaring of the anterior teeth.

PMID- 10961785
TI  - Orthodontic correction of a transposed maxillary canine and lateral incisor.
AB  - Tooth transposition presents a major challenge in the correction of a
      malocclusion. A dental transposition is an uncommon disturbance affecting 0.4% of
      the population, yet the treatment difficulties make this anomaly an occurrence of
      orthodontic interest and a source of clinical interest. This case report shows
      the unilateral transposition of a maxillary canine with a lateral incisor that
      was treated by orthodontically reversing the transposed tooth positions. An
      analysis of the clinical concerns in the treatment of this problem is presented.

PMID- 10961786
TI  - Adjunctive thalidomide therapy of childhood tuberculous meningitis: possible anti
      inflammatory role.
AB  - The objective of this study was to determine the safety and tolerability of the
      immunomodulatory agent thalidomide as adjunct therapy in children with
      tuberculous meningitis. Children with stage 2 tuberculous meningitis received
      oral thalidomide for 28 days in a dose-escalating study, in addition to standard
      four-drug antituberculosis therapy, corticosteroids, and specific treatment of
      complications such as raised intracranial pressure. Clinical and laboratory
      evaluations were carried out. Fifteen patients (median age, 34 months) were
      enrolled. Thalidomide was administered via nasogastric tube in a dosage of 6
      mg/kg/day, 12 mg/kg/day, or 24 mg/kg/day. The only adverse events possibly
      related to the study drug were transient skin rashes in two patients. Levels of
      tumor necrosis factor-alpha in the cerebrospinal fluid decreased markedly during
      thalidomide therapy. Clinical outcome and neurologic imaging showed greater
      improvement than that experienced with historical controls. Thalidomide appeared
      safe and well tolerated in children with stage 2 tuberculous meningitis and could
      have important anti-inflammatory effects. These promising results have led us to
      embark on a randomized, double-blind, placebo-controlled trial of the efficacy of
      thalidomide in tuberculous meningitis.

PMID- 10961787
TI  - Clinical correlates of brain morphometric features of subjects with low
      functioning autistic disorder.
AB  - Numerous neuropathologic and imaging studies have reported different structural
      abnormalities in the brains of autistic subjects. However, whether or not the
      degree of brain abnormality is correlated with the severity of developmental
      impairment in autistic disorder is still unknown. The midsagittal area of the
      cerebrum, corpus callosum, midbrain, cerebellar vermis, and vermal lobules VI and
      VII was measured by means of magnetic resonance imaging in 22 boys with low
      functioning autistic disorder and in 11 age-matched normal controls. Morphometric
      measures were statistically compared between groups and correlated with age and
      scores on the Psychoeducational Profile-Revised and the Childhood Autism Rating
      Scale. A significant negative correlation was found between midsagittal area of
      the cerebrum and age in patients with autistic disorder, and a positive
      correlation was found between the midsagittal area of the midbrain and some
      subscales of the Psychoeducational Profile-Revised.

PMID- 10961788
TI  - Vagus nerve stimulation treatment for Lennox-Gastaut syndrome.
AB  - Lennox-Gastaut syndrome is a severe age-specific epilepsy syndrome that presents
      with medication-resistant seizures in childhood. Antiepileptic drugs are the
      mainstay of treatment. Nonpharmacologic treatments include corpus callosum
      section and the ketogenic diet. However, no single treatment is safe and
      effective. We treated 13 patients with Lennox-Gastaut syndrome between the ages
      of 4 and 44 years (mean, 16.7 years) with vagus nerve stimulation. During the
      first 6 months of treatment, vagus nerve stimulation produced a median seizure
      rate reduction of 52% (range, 0% to 93%; P = .04). At 6 months of follow-up,
      three patients had a greater than 90% reduction in seizures, two had a greater
      than 75% reduction, one had a greater than 50% reduction, and six had at least a
      25% reduction. One patient did not improve. No patient worsened after initial
      improvement. Side effects, including hoarseness, coughing, and pain in the
      throat, were transient and tolerable. No patient discontinued vagus nerve
      stimulation. Our results suggest that vagus nerve stimulation could be an
      effective and safe adjunct therapy for the treatment of Lennox-Gastaut syndrome.

PMID- 10961789
TI  - Progressive infantile axonal polyneuropathy.
AB  - Polyneuropathies are relatively uncommon in early infancy and the majority of
      affected children are found to have hypomyelinating neuropathies. Axonal
      sensorimotor neuropathies have been described in childhood but the majority of
      affected children present at or after 6 months of age, have nonprogressive
      courses, and achieve the ability to walk, albeit late. Here we present three
      infants with infantile progressive axonal polyneuropathy from two families with
      nonconsanguineous parents. Each child presented shortly after the neonatal period
      and with rapid progression to quadriplegia. Involvement of the lower cranial
      nerves, phrenic nerves, or both was present in each child. Electrophysiology was
      diagnostic in each child. While the diagnosis of spinal muscular atrophy was
      considered in each case, clinical presentation, biopsies, and genetic testing
      were inconsistent with this diagnosis. Recognition of this early form of
      progressive axonal neuropathy is important as respiratory compromise occurred
      early and the condition showed familial inheritance in two of our patients.

PMID- 10961790
TI  - Three children with a syndrome of obesity and overgrowth, atypical psychosis, and
      seizures: a problem in neuropsychopharmacology.
AB  - Three children presented with a complex syndrome of atypical psychotic and
      extremely immature behavior, obesity and overgrowth, borderline retardation, and
      seizures (prominent in two). Weight overgrowth exceeded height overgrowth and was
      stratospheric (up to 8 SD above mean). Obesity seemed related to lack of satiety.
      The cases fit no known condition: hypothalamic damage, Sotos' syndrome, and
      Prader-Willi syndrome were excluded. Empirical treatment with anticonvulsants
      (carbamazepine and acetazolamide) together with psychotropic agents (selective
      serotonin reuptake inhibitors and risperidone) controlled seizures, improved
      behavior, and stopped weight gain in each patient. We have not found this
      syndrome previously described. The etiology is unknown: perinatal encephalopathy
      could be a factor in the two patients with prominent seizures; in the third,
      familial major affective disorder is implicated. Medication responses suggest a
      low-serotonin state underlying the lack of satiety, an imbalance of serotonin and
      noradrenergic modulation in the hypothalamus, and epileptogenic disorders (or
      affective disorder responsive to anticonvulsants in one case) involving these
      same systems.

PMID- 10961791
TI  - Abnormal sudomotor function in the hypomelanotic macules of tuberous sclerosis
      complex.
AB  - To investigate the integrity of sympathetic innervation in the hypomelanotic
      macules of tuberous sclerosis complex, we studied sudomotor function in nine
      patients with tuberous sclerosis complex. Postganglionic sudomotor function was
      assessed using the Silastic imprint test in nine patients with tuberous sclerosis
      complex who have at least one hypomelanotic macule greater than 2 cm in diameter.
      Sweating was induced by iontophoresis with 0.5% pilocarpine nitrate and sweat
      droplets were counted under a microscope using a 1 x 1 cm grid. Silastic imprint
      testing of an analogous skin area contralateral to the hypomelanotic macule was
      measured as a control. Sweat volume quantitation using sweat collectors was
      performed in five of the subjects. The sweat volume collected from the
      hypomelanotic macule was reduced compared to the control skin in four of the five
      subjects. Sweat droplet counts from the hypomelanotic macule were significantly
      reduced in only one of nine subjects. These data suggest that, although there is
      no difference in the number of functioning sweat glands in most hypomelanotic
      macules, the sweat glands produce less sweat (ie, decreased sweat volume) than in
      normal skin. We hypothesize that focal abnormalities of sympathetic innervation
      might be responsible for the hypomelanotic macules of tuberous sclerosis complex.

PMID- 10961792
TI  - Preschoolers classified as having attention-deficit hyperactivity disorder
      (ADHD): DSM-IV symptom endorsement pattern.
AB  - In the present study, 50 preschoolers were formally and independently classified
      using both the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition (DSM-IV) and third edition-revised (DSM-III-R) criteria for attention
      deficit hyperactivity disorder (ADHD). The sample consisted of 25 preschoolers
      classified as having ADHD and 25 typically developing preschoolers for
      comparison; the sample was matched on gender, age, and socioeconomic status. All
      50 preschoolers were without neurologic or neurodevelopmental disorders,
      oppositional defiant disorder, or language delay. There were four key findings:
      first, of the 25 preschoolers with ADHD, DSM-IV classification was as follows:
      hyperactive-impulsivity type (68%), combined type (28%), and inattentive type
      (4%). Second, the DSM-IV profiles showed that several symptoms were either
      infrequently endorsed by parents, reflecting limited applicability to
      preschoolers with ADHD, or frequently endorsed by parents of typically developing
      preschoolers, thus reducing their diagnostic value. Third, of the 25 preschoolers
      classified as having ADHD using DSM-IV criteria, 16% would not have been
      classified as having ADHD using the DSM-III-R criteria. The DSM-IV criteria
      therefore appear to be more lenient than the DSM-III-R criteria for this age
      group. Fourth, two symptoms that were not included in the DSM-IV, but were part
      of the DSM-III-R, were found to have clinical value for differentiating
      preschoolers with ADHD from their typically developing peers.

PMID- 10961793
TI  - Methylenetetrahydrofolate reductase deficiency: importance of early diagnosis.
AB  - Methylenetetrahydrofolate reductase deficiency is the most common inborn error of
      folate metabolism and should be suspected when homocystinuria is combined with
      hypomethioninemia. The main clinical findings are neurologic signs such as severe
      developmental delay, marked hypotonia, seizures, microcephaly, apnea, and coma.
      Most patients present in early life. The infantile form is severe, with rapid
      deterioration leading to death usually within 1 year. Treatment with betaine has
      been shown to be efficient in lowering homocysteine concentrations and returning
      methionine to normal, but the clinical response is variable. We report two
      brothers with methylenetetrahydrofolate reductase deficiency: the first was
      undiagnosed and died at 8 months of age from neurologic deterioration and apnea,
      while his brother, who was treated with betaine from the age of 4 months, is now
      3 years old and has developmental delay.

PMID- 10961795
TI  - Benign childhood epileptic syndromes with occipital spikes: new classification
      proposed by the International League Against Epilepsy.
AB  - In a recent proposal, the Commission on Classification and Terminology of the
      International League Against Epilepsy recognized early-onset childhood epilepsy
      with occipital spikes (Panayiotopoulos type), differentiating it from the only
      other type of childhood epilepsy with occipital spikes previously accepted: late
      onset childhood epilepsy with occipital spikes (Gastaut type). The importance of
      this newly recognized syndrome of benign childhood partial seizures is that it is
      very common-only 2.4 times less frequent than benign rolandic epilepsy, and of
      equally excellent prognosis. It is characterized by a unique seizure type
      comprising a combination of autonomic and behavioral disturbances, vomiting,
      deviation of the eyes, and often with impairment of consciousness that can
      progress to convulsions. These commonly last for more than 3 minutes and in one
      quarter of cases for hours. One or more of these symptoms can predominate or be
      absent. Eyes can remain open without deviation, ictal vomiting might not occur,
      and autonomic and behavioral disturbances can predominate, particularly in the
      early stages of the ictus, and be missed in nocturnal seizures. Age at onset is 5
      years, with a singular or a median of three seizures, which are predominantly
      nocturnal. Interictal electroencephalography (EEG) frequently shows occipital
      paroxysms or occipital spikes but one-fifth of the cases have only extraoccipital
      spikes on normal EEG. Treatment might not be needed. Panayiotopoulos syndrome,
      like rolandic epilepsy, needs recognition by the general pediatrician because of
      the invariably excellent prognosis and also because it can be misdiagnosed as an
      acute cerebral insult.

PMID- 10961794
TI  - Dengue infection presenting with central nervous system manifestation.
AB  - The objective of this study was to investigate the possibility of dengue virus
      infection causing an abnormal neurologic presentation. Between 1996 and 1998, all
      pediatric patients with clinical manifestations of encephalitis-like illness who
      were admitted to the Department of Pediatrics, Siriraj Hospital were
      prospectively studied for any evidence of dengue virus infection. The diagnosis
      of dengue virus infection was based on mosquito viral isolation and serologic and
      polymerase chain reaction (PCR) evidence. Of 44 patients with the preliminary
      diagnosis of acute viral encephalitis, 8 were diagnosed with dengue infection.
      All of these 8 patients were diagnosed by serology. In addition to the serologic
      diagnosis, four also had positive PCR, one had positive viral isolation, and one
      had both positive PCR and viral isolation. Only two patients were diagnosed by
      serologic evidence alone. All except one had clinical courses and laboratory
      findings compatible with typical dengue infection. All had obvious encephalitic
      clinical manifestations with normal cerebrospinal fluid findings except one
      patient, who had mildly increased cerebrospinal fluid protein. All of these
      patients recovered completely and had benign clinical courses except one patient,
      who developed leakage symptoms. None had liver failure. Dengue virus can cause
      acute encephalopathy with fever. It can masquerade as other types of acute viral
      encephalitis. However, its clinical course and prognosis are usually favorable.

PMID- 10961796
TI  - Kearns-Sayre syndrome with a novel mitochondrial DNA deletion.
AB  - We describe a 17-year-old boy with a clinical neurologic picture consistent with
      Kearns-Sayre syndrome. His manifestations included progressive external
      ophthalmoplegia, bilateral ptosis, retinitis pigmentosa, and muscle weakness. He
      was found to harbor an abundant novel deletion in skeletal muscle mitochondrial
      DNA. Biochemical analysis of the patient's biopsied skeletal muscle showed that
      the specific activities of all four respiratory complexes with mitochondrial DNA
      encoded subunits were markedly reduced in contrast to normal activity levels of
      entirely nuclear DNA-encoded enzyme activities (eg, complex II and citrate
      synthase). Ultrastructural analysis also indicated the presence of strikingly
      abnormal mitochondria with both unusual cristae and frequent paracrystalline
      inclusions. The great amount of the deleted mitochondrial DNA in this patient's
      muscle, as well as the concomitant reduction in specific respiratory complex
      activity, suggests that the mitochondrial DNA deletion plays a role in the
      pathogenesis of this neurologic disease.

PMID- 10961797
TI  - Successful treatment for stroke in a child using recombinant tissue plasminogen
      activator.
AB  - Stroke in childhood is often catastrophic, with major sequelae. We report the
      first successful use of recombinant tissue plasminogen activator for arterial
      stroke in a child. The patient recovered with no neurologic deficit.

PMID- 10961798
TI  - Intracranial fibromuscular dysplasia in a six-year-old child: a rare cause of
      childhood stroke.
AB  - Intracranial fibromuscular dysplasia is a nonatheromatous angiopathy that most
      commonly affects adult women and is rarely recognized in children. Symptoms
      include stroke and headache, although the vasculopathy may be asymptomatic.
      Diagnosis is based on angiographic appearance, commonly described as a "string of
      beads." The etiology of intracranial fibromuscular dysplasia is not known,
      although possible causes include genetic predisposition, trauma, and underlying
      connective tissue disease. Treatment of intracranial fibromuscular dysplasia is
      largely supportive once symptoms become manifest. We report a 6-year-old girl who
      presented to our center for further evaluation of a large left middle cerebral
      artery distribution infarction. The patient was previously healthy, without known
      risk factors for stroke. Initial symptoms consisted of a dense global aphasia and
      a right hemiparesis. On arrival, the patient's aphasia had improved but she
      continued to have significant deficits in both receptive and expressive language
      as well as residual right hemiparesis. Magnetic resonance imaging and
      conventional angiographic studies demonstrated characteristic beading of the
      distal portion of the left internal carotid artery, as well as the proximal
      middle cerebral artery. Laboratory evaluation, echocardiogram, and renal
      ultrasound were normal. The renal vasculature did not demonstrate evidence of
      intracranial fibromuscular dysplasia. In conclusion, intracranial fibromuscular
      dysplasia should be considered in the differential diagnosis of childhood stroke.
      When recognized, other sites of vascular involvement should be sought, and
      consideration of underlying disorders is important, as connective tissue
      disorders have been associated with a propensity to develop this vascular
      abnormality. Careful follow-up is warranted, due to possible progression of
      disease.

PMID- 10961799
TI  - Hmong child with myoclonic seizure disorder.

PMID- 10961800
TI  - Morphological and functional study of regenerated chorda tympani nerves in
      humans.
AB  - It is still unclear whether the chorda tympani nerves in humans regenerate after
      being severed during middle ear surgery, although functional studies have
      demonstrated recovery of taste 1 to 2 years after surgery. To date, 12 cases of
      regenerated chorda tympani nerves have been found in our series of patients
      during secondary surgery. The regenerated nerves of 3 cases of the 12 were
      removed as samples during secondary surgery to detect regenerated myelinated
      axons. All regenerated nerves were in the submucosal connective tissue layer of
      the reconstructed eardrum. In the regenerated nerves, myelinated nerve fibers
      existed in a small fascicle or in connective tissue, but the number of myelinated
      axons was low compared with that in normal subjects ( 1.752 +/- 78; n = 3), and
      the distribution was sparse. The total number of regenerated myelinated axons
      varied from 141 (8.3%) to 979 (55.9%). From a functional study using
      electrogustometry, incomplete recovery of electrogustation was observed in all 3
      cases before secondary surgery, suggesting that chorda tympani nerves actually
      regenerate in the middle ear and do function.

PMID- 10961801
TI  - Use of methotrexate for autoimmune hearing loss.
AB  - To assess the efficacy of low-dose methotrexate (MTX) given long-term for the
      treatment of autoimmune hearing loss, we performed a prospective open-label study
      of 11 patients with treatment-refractory autoimmune hearing loss. All patients
      had ongoing episodic worsening of hearing in 1 or both ears before enrollment
      despite traditional medical therapy. The MTX dose was 7.5 to 17.5 mg/wk. Hearing
      loss and vertigo were evaluated at baseline and at completion of the study.
      Hearing improvement was defined as an improvement in the pure tone threshold (PT)
      average of >10 dB or an increase in speech discrimination (SD) of >15%, whereas
      worsening was defined as a worsening of >10 dB in PT or a decrease of >15% in SD
      in at least 1 ear. The MTX was well tolerated. Among the 6 patients with
      Meniere's disease. 4 had improvement or resolution of vertigo, while 2 had no
      improvement. Disequilibrium improved in all 3 patients with Cogan's syndrome.
      According to the parameters defined above, hearing improved in 9 patients (82%),
      was unchanged in 1 patient (9%), and worsened in 1 patient (9%). Long-term low
      dose MTX therapy may be a useful therapy for some patients who have hearing loss
      with a presumptively autoimmune-mediated component that is refractory to
      traditional therapies.

PMID- 10961802
TI  - Effect of 7-nitroindazole upon cochlear dysfunction induced by transient local
      anoxia.
AB  - The purpose of the present study was to further elucidate how nitric oxide (NO)
      is involved in cochlear anoxia-reperfusion injury. Transient local anoxia of the
      cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by
      transiently compressing the labyrinthine artery through a skull base approach. 7
      Nitroindazole (7NI), a relatively selective neuronal nitric oxide synthase (nNOS)
      inhibitor. was intraperitoneally administered to the guinea pigs 30 minutes
      before the onset of local anoxia. The compound action potential (CAP) thresholds
      were measured before the administration of 7NI and 4 hours after the onset of
      reperfusion. A statistically significant reduction in the postanoxic CAP
      threshold shift from the preadministration value was observed in the 7NI
      administered animals as compared with the control animals after 15- and 30-minute
      periods of anoxia. These results confirm the involvement of NO and nNOS in the
      cochlear injury induced by transient local anoxia.

PMID- 10961803
TI  - Olfactory mucosal findings in patients with persistent anosmia after endoscopic
      sinus surgery.
AB  - Sixty-three biopsy specimens were obtained from the olfactory region of 15
      patients with persistent anosmia and 6 patients with normosmia after sinus
      surgery. Immunohistochemical examination of all specimens with microtubule
      associated protein 5 (MAP5) antisera demonstrated olfactory epithelium in 11 of
      18 specimens from normosmic patients and in 12 of 45 samples from anosmic
      patients. There was a significant difference in the proportion of specimens
      containing olfactory epithelium between the two groups of patients. In normosmic
      patients, most of the biopsy samples contained normal-appearing olfactory tissue.
      However, 2 main patterns of histologic findings were noted in the olfactory
      mucosa of anosmic patients. First, the olfactory receptor cells were remarkably
      decreased in number. Second, the orderly arrangement of cells characteristic of
      normal olfactory epithelium was lost, demonstrating a degenerative appearance.
      These data suggest that olfactory epithelium can be degenerated even in chronic
      sinusitis and thereafter extensively replaced with respiratory epithelium,
      resulting in increased sampling error. Moreover, an unimproved olfactory deficit
      after sinus surgery may be due to the abnormalities observed at the olfactory
      epithelium level.

PMID- 10961804
TI  - Ultrastructural changes in platelet activating factor-induced epithelial damage
      in rabbit maxillary sinus mucosa.
AB  - Platelet activating factor (PAF), a potent chemical mediator in inflammation and
      allergic reaction, has been thought to induce mucociliary inhibition and
      epithelial damage in the airway mucosa. However, several recent papers have
      reported that PAF may not readily damage the airway epithelium. The aim of this
      study was to elucidate the pathogenesis of PAF-induced epithelial damage in terms
      of ultrastructural changes. Sixteen micrograms of PAF (1 mL of 16 microg/mL) was
      administered into the maxillary sinuses of rabbits. The rabbits were divided into
      2 groups according to time intervals, and the antral mucosa was taken 1 and 3
      days after administration of PAF. The tissue was processed for routine
      transmission electron microscopy. No epithelial degeneration was observed other
      than platelet aggregation, red blood cell stasis, and swelling of the endothelial
      cells 1 day after administration of PAF. Migration of inflammatory cells into the
      perivascular connective tissue, infiltration of eosinophils into the
      subepithelial and intraepithelial spaces, and vacuolar degeneration of the
      epithelial cells with focal loss of cilia were seen 3 days after administration
      of PAF. In conclusion, PAF induced infiltration of eosinophils into the
      epithelium, and resulted in epithelial degeneration that varied according to the
      time interval. Our findings suggest that PAF may cause epithelial damage through
      a series of secondary events, probably due to cytotoxicity of eosinophils
      infiltrating the epithelium.

PMID- 10961805
TI  - Acquired tracheoesophageal fistula in critically ill patients.
AB  - Acquired benign tracheoesophageal fistula (TEF) is an infrequent complication of
      prolonged intubation and tracheostomy. Not infrequently, it is associated with
      severe circumferential malacia of the trachea and a need for concomitant
      correction of both. Controversy exists as to whether this should be performed in
      a single-stage or a 2-stage procedure. Four patients with acquired TEF underwent
      operation in a tertiary referral medical center between 1995 and 1997. The
      operations were performed through either an anterior (3) or a lateral (1) neck
      approach. Three patients underwent closure of the fistula with tracheal resection
      and anastomosis in a single stage and are doing well. One patient with complete
      subglottic stenosis underwent closure of the TEF and was planned for tracheal
      reconstruction in a second stage. This patient died in the early postoperative
      period. The complications included aspiration of blood leading to pneumonia (2),
      spontaneously resolving pneumomediastinum (1), subcutaneous emphysema (2), and
      cardiac arrhythmia ( 1). Residual fistula, noted in 1 patient, was treated
      conservatively and resolved spontaneously within several weeks. We conclude that
      acquired TEF is amenable to repair through a cervical approach. A single-stage
      correction of the TEF with reconstruction of the trachea is suitable and
      successful in most patients. Several stages seem justified when concurrent
      laryngotracheal reconstruction is needed.

PMID- 10961806
TI  - Postintubation interarytenoid adhesion.
AB  - Interarytenoid fibrous adhesion is a poorly recognized complication of intubation
      and is frequently confused with bilateral vocal cord paralysis. Early diagnosis
      and treatment is essential for optimal management. Otolaryngologists should
      constantly remain alert for interarytenoid fibrous scar to establish the
      diagnosis as early as possible, optimizing the probability of restoring normal
      breathing and quality of life and avoiding an unnecessary tracheotomy. Surgical
      laser reduction is appropriate in all cases when other miscellaneous laryngeal
      injury lesions are eliminated. Direct laryngoscopy with careful examination of
      the posterior commissure and laryngeal electromyography are the 2 main clinical
      diagnostic aids contributing to establish the diagnosis.

PMID- 10961807
TI  - Perceptual characteristics of adductor spasmodic dysphonia.
AB  - The evaluation of perceptual symptoms is one of the mainstays in the diagnostic
      workup of adductor spasmodic dysphonia (ADSD). The most widely used perceptual
      rating system is the GRBAS scale. However, with this system, not all audible
      features of ADSD can be described. Therefore, we extended the GRBAS system by 6
      parameters. The aim of this study was assessment of the perceptual
      characteristics of ADSD with the "extended" GRBAS system and evaluation of its
      reproducibility. Seventy-seven patients were scored independently by 3
      experienced observers quantifying the voice sound profile. Cluster analysis
      distinguished 4 different voice types. Intraobserver and interobserver agreement
      among 8 less-experienced observers appeared fair-to-good. This study demonstrates
      that the "extended" GRBAS system is suitable for perceptual characterization of
      ADSD. On the grounds of the fair-to-good interobserver variability, it is
      appropriate for clinical use. Moreover, 4 different voice clusters of ADSD were
      identified, with significant differences in voice and demographic parameters.

PMID- 10961808
TI  - CD34+ immune suppressive cells in the peripheral blood of patients with head and
      neck cancer.
AB  - Patients with head and neck squamous cell carcinoma (HNSCC) have profound defects
      in their immune defenses. Using immunofluorescent staining and flow cytometric
      analysis, we found that most patients with HNSCC have increased levels of CD34+
      cells within their peripheral blood. These circulating CD34+ cells contribute to
      the depressed functional competence of the peripheral blood T-lymphocytes. This
      was demonstrated by the increased level of proliferative responsiveness to
      interleukin-2 by the patients' peripheral blood T-cells after depletion of CD34+
      cells. These results show the importance of CD34+ cells in contributing to the
      depression of T-lymphocyte function in patients with HNSCC and suggest that
      strategies designed to reduce the levels of circulating CD34+ cells may enhance
      the immune reactivity of the patients' circulating T-lymphocytes against the
      HNSCC.

PMID- 10961809
TI  - Use of a coincidence gamma camera to detect primary tumor with 18fluoro-2-deoxy
      glucose in cervical lymph node metastases from an unknown origin.
AB  - This study was performed to evaluate the ability of a dual-head gamma camera with
      18fluoro-2-deoxy-glucose coincidence detection emission tomography (FDG-CDET) to
      detect primary tumors in patients with cervical lymph node metastases of head and
      neck squamous cell carcinoma from an unknown origin. From 60 patients with
      untreated head and neck squamous cell carcinoma, we selected 4 in whom no
      evidence of the primary's origin was found by the conventional methods used for
      the evaluation of head and neck tumors. In addition to the panendoscopy, chest
      radiography, a computed tomography (CT) scan, and FDG-CDET were performed. Both
      FDG-CDET and the CT scan located cervical lymph node metastases. In addition, FDG
      CDET located the primary tumor in 3 of the 4 patients, and the tumors were
      confirmed with histopathologic findings. In contrast, the CT scan detected the
      primary tumor in none of them. FDG tomography performed on a coincidence gamma
      camera appears to be a successful new tool in detecting occult primary tumors in
      head and neck carcinoma, and is useful in guiding endoscopic biopsies. It has,
      further, the important potential ability to detect distant metastases on whole
      body images.

PMID- 10961810
TI  - Objective comparison of shoulder dysfunction after three neck dissection
      techniques.
AB  - A prospective study with subjective evaluation of shoulder pain and objective
      evaluation of shoulder muscle strength by isokinetic testing and
      electromyographic and electroneurographic studies of spinal accessory nerve
      function was performed on patients who had undergone neck dissection procedures.
      Twenty-one patients with head and neck cancer were enrolled in this study. Three
      types of neck dissection were performed: 7 selective neck dissections, 9 modified
      radical neck dissections, and 5 radical neck dissections. All patients who
      underwent radical neck dissection had shoulder pain, and 80% of them had shoulder
      droop after the operation. In the patients who underwent selective neck
      dissection, the electromyographic findings of the spinal accessory nerve were
      relatively normal. Their shoulder strength was sometimes decreased at I month
      after operation, but it had returned to preoperative strength by the 6-month
      follow-up visit. These findings suggested that patients who underwent selective
      neck dissection had the least damage to spinal accessory nerve function and the
      least shoulder disability after neck dissection.

PMID- 10961811
TI  - Timing of swallowing events after single-modality treatment of head and neck
      carcinomas with radiotherapy.
AB  - This paper reports the results of a preliminary study designed to evaluate
      swallowing function in 20 patients 1 year after successful treatment of head and
      neck carcinomas with radiotherapy. The timing of swallowing events was evaluated
      by videofluoroscopy. The mean values for each measure were compared to the
      normative data from 60 control subjects. The radiotherapy patients demonstrated
      prolonged pharyngeal bolus transit and a delay of laryngeal closure. Hyoid bone
      elevation began late relative to the onset of bolus movement. A strong trend
      toward a delay in hyoid elevation relative to bolus movement was demonstrated.
      The time required for the hyoid bone to reach maximal elevation did not differ
      from that in normals, but the hyoid was held in an elevated position for a longer
      period of time. As a result of changes in hyoid movement, the upper esophageal
      sphincter tended to open early relative to the arrival of the bolus. In
      conclusion, changes in deglutition occur after radiotherapy, presumably as an
      adaptation to changes in tissue compliance.

PMID- 10961813
TI  - Epiglottic hypoplasia associated with lacrimo-auriculo-dental-digital syndrome.
AB  - We present a case of a young boy with clinical manifestations of lacrimo-auriculo
      dental-digital syndrome (LADD) with the additional finding of a hypoplastic
      epiglottis that caused airway obstruction at birth. We also reviewed the 30 cases
      of LADD that have been reported since 1967. It is a rare syndrome that includes
      lacrimal system, aural, digital, and dental anomalies. Our patient has lacrimal
      duct obstruction, deficient tissue in the inferior portion of the ear pinnae, and
      a hypoplastic epiglottis with collapse of the supraglottic tissue. Many findings
      of LADD are recognizable at birth. The clinical spectrum has widened with more
      case reports. Our patient adds a life-threatening airway abnormality, a
      hypoplastic epiglottis, to the clinical spectrum of LADD.

PMID- 10961812
TI  - Massive epistaxis after rupture of intracavernous carotid artery aneurysm. Case
      report.
AB  - We present a case of massive epistaxis caused by an internal carotid artery
      aneurysm. The initial treatment with endovascular balloon embolization failed as
      a result of balloon displacement. After rebleeding, the intracavernous aneurysm
      was treated with an endovascular detachable balloon embolization technique, which
      resulted in cessation of epistaxis. The different treatment options for
      interventional radiology and management of ruptured carotid artery aneurysms are
      discussed.

PMID- 10961814
TI  - Paraclinoid internal carotid artery aneurysm presenting as massive epistaxis.

PMID- 10961815
TI  - Scintigraphic monitoring of swallowing rehabilitation after horizontal
      supraglottic laryngectomy.

PMID- 10961816
TI  - Outcome of very-low-birth-weight infants at 1 and 2 years of age. The importance
      of early identification of neurodevelopmental deficits.
AB  - The developmental and neurologic outcome of very-low-birth-weight infants (n=76)
      at 1 and 2 years, corrected for postconceptional age, and variables predicting
      outcome were assessed. At 1 year 24% of tile children were neurologically normal
      and at 2 years 61%. Developmental status was evaluated by use of the Griffiths
      Developmental Scales. The rate of cognitively normal children remained constant
      (58% at 1 year and 59% at 2 years) indicating that developmental status at 1 year
      was predictive for the second year. This early period is important, therefore,
      for the identification of developmental deficits and for establishing early,
      adequate interventions.

PMID- 10961817
TI  - Spontaneous-onset atrial fibrillation in a toddler with review of mechanisms and
      etiologies.
AB  - Atrial fibrillation is a relatively rare form of arrhythmia in the pediatric
      population. When it is seen in an infant or child, it is often associated with a
      structural heart abnormality, particularly after surgical repair or palliation of
      congenital heart disease. Other episodes may be associated with metabolic
      derangements. This report discusses the unique case of a toddler with new-onset
      atrial fibrillation that was devoid of a readily identifiable etiology. It also
      reviews the literature and the implications of such a case for the primary care
      practitioner.

PMID- 10961818
TI  - UTI: diagnosis and evaluation in symptomatic pediatric patients.
AB  - We retrospectively reviewed data on 260 hospitalized pediatric patients with
      symptomatic urinary tract infection (UTI). To ascertain the colony-forming units
      (CFU)/mL compatible with the diagnosis of UTI, a culture from a catheterized
      urine specimen containing >1,000 CFU/mL was considered diagnostic of UTI and
      resulted in imaging by renal ultrasound, voiding cystourethrography, and renal
      nuclear scan with Tc99m dimercaptosuccinic acid (DMSA). A positive DMSA renal
      scan is indicative of pyelonephritis. We used logistic regression analysis to
      determine which patient characteristics were predictive of pyelonephritis. We
      determined that, in hospitalized pediatric patients, the colony count of the
      positive urine culture, the type of organism grown in culture, and the voiding
      cystourethrography (VCUG) result (positive or negative for vesicoureteral reflux)
      did not predict which patients had pyelonephritis. In females, advancing age of
      the patient and positive renal ultrasound results were predictive of which
      patients had pyelonephritis when we controlled for other factors. We feel this
      emphasizes the importance of a thorough evaluation of hospitalized symptomatic
      patients, including patients with colony counts of 1,000 to 50,000 CFU/mL, to
      locate the level of infection and plan appropriate therapy.

PMID- 10961819
TI  - The academic children's hospital primary care clinic: responding to the
      challenges of a changing health care environment.
AB  - Academic medical centers have encountered increasing fiscal challenges as the
      paradigm in health care has shifted from traditional fee-for-service
      reimbursement to systems of managed care. Most academic centers have maintained
      primary care clinics, which have served as "educational laboratories" for
      students and trainees. Largely providing care to underserved patients, academic
      primary care clinics have been heavily dependent on Medicaid reimbursement for
      support. Given the realities of a rapidly changing health care environment,
      academic primary care clinics have been challenged to respond with innovation and
      creativity in order to remain viable. The pediatric primary care clinic at
      Rainbow Babies & Children's Hospital of University Hospitals of Cleveland
      initiated a reorganization program with the goal of ensuring that patients
      receive quality, cost efficient care and that students and pediatric residents
      receive first-rate ambulatory education in a fiscally responsible setting.
      Fundamental was the setting of priorities for patient care and service while
      promoting an environment conducive to medical education. Educational programs
      were segregated into a well-defined educational "module," and various initiatives
      were advanced emphasizing patient access, consistency of care, efficient use of
      space and personnel resources, limitation of inappropriate use of costly after
      hours resources, and identification and coordination of care for patients with
      chronic illness and/or at high risk for medical complications. Three years after
      the instituting of fundamental organizational change, objective measures of cost
      efficiency and selected quality measures compare quite favorably with a broad
      range of primary care providers throughout the region. If academic medical
      centers are to remain leaders in ambulatory pediatric education, energetic,
      proactive, and thoughtful responses to the rapidly changing global health care
      environment will be necessary.

PMID- 10961820
TI  - Urban emergency department utilization by adolescents.
AB  - This study describes urban emergency department (ED) utilization and follow-up
      referral patterns among adolescents. ED visits for 14-19-year-old patients at an
      urban university hospital with adjacent adult and pediatric emergency departments
      during specified months in 1993 were retrospectively reviewed. A subgroup (n=150)
      was randomly selected for detailed chart review. One thousand six hundred and
      thirty-six adolescents were seen in the ED during the study period. Public
      assistance (n=763; 47%) and commercial insurance (n=480; 29%) were the most
      common forms of insurance, followed by self-pay (n=357; 22%). The majority of
      triage codes for ED visits were nonurgent (n=140; 93%). Twenty-five patients
      (17%) were not referred for follow-up upon ED discharge. Adolescents on public
      assistance or without insurance may frequently utilize an urban ED for nonurgent
      medical problems. A group of patients did not identify a primary care provider at
      triage and were not referred for follow-up. Defining medical problems for which
      adolescents utilize the ED may help health professionals to tailor community
      resources to better serve adolescent health care needs.

PMID- 10961821
TI  - Effect of allergy testing to tobacco leaf on passive smoke exposure in a
      pediatric pulmonary/allergy practice.

PMID- 10961822
TI  - Incontinence in myelodysplasia: imipramine hydrochloride revisited.

PMID- 10961823
TI  - Neonatal idiopathic scrotal hemorrhage: patient reports.

PMID- 10961824
TI  - False-positive urine cultures using bag collection.

PMID- 10961825
TI  - Perianal streptococcal disease.

PMID- 10961827
TI  - State maternal and child expenditures and low birthweight infants: a descriptive
      analysis.
AB  - This study examines the relationship over time between state public health
      spending for maternal and child health and rates of low birthweight infants.
      Using expenditure data from the Public Health Foundation and National Center for
      Health Statistics, we compare the 10 states with the highest and lowest rates of
      low birthweight infants in 1980 and the 10 states with the most improved and
      least improved low birthweight rates over a 10-year period. We hypothesize that
      the 10 states with the best low birthweight rates and 10 states with the most
      improvement in low birthweight rates will be the states with the highest levels
      of maternal and child health expenditures per birth. We find no support for the
      hypothesis in either group of states. At the state level, maternal and child
      public health expenditures do not appear correlated with states that are the most
      successful or are making the most improvement in low birthweight infants.

PMID- 10961826
TI  - Giant rectosigmoid stone bezoar in a child.

PMID- 10961828
TI  - Financial managers' costing expertise is needed in clinical trials.
AB  - In addition to providing comparable and verifiable evidence regarding outcomes,
      clinical trials could also serve as sources of accurate and replicable financial
      information. Trial reports that identify expenses associated with effective
      diagnostic and therapeutic interventions enable cost controls. Standardized cost
      calculations could help clinicians and administrators identify more efficient
      health care technologies. Unfortunately, relatively few published trials include
      economic analyses and when they do, data are incomplete. Based on analyses of 97
      clinical trial reports, this article proposes a standard costing format. Health
      care financial managers have the costing expertise necessary to implement and
      interpret standardized cost calculations for clinical trials. With the active
      involvement of financial managers, a standard costing format for clinical trials
      can be achieved.

PMID- 10961829
TI  - Incentivising appropriate care: the case of immunizations.
AB  - Incentivising appropriate care is a two-way street. Patients need to take greater
      responsibility and provider payment systems need to reward the best quality care.
      Today we are seeing the reemergence of many vaccine-preventable diseases that we
      thought were eradicated long ago for all practical purposes. In the U.S.,
      diphtheria, polio, measles, mumps, and rubella all are on an upsurge. In this era
      of stringent cost containment and "managed care," preventive childhood
      immunizations offer one of the highest financial returns on investment we can
      achieve. So why have our inner cities become worse than some third-world
      countries in terms of low immunization rates for preschool age children and high
      infant mortality? We argue that "it's the money."

PMID- 10961830
TI  - Variation in state Medicaid expenditures 1984-92: the behavioral impact of the
      matching federal grant.
AB  - Although the federal Medicaid matching grant was designed to decrease disparities
      in state Medicaid spending, significant inequities persist. A potential reason
      for this is that states substitute federal for state funds and therefore
      expenditures in low-income, low-spending states are not stimulated. This study
      uses a fixed-effects model on pooled state expenditure data for 1984-92 to
      examine the fiscal response of states to the federal Medicaid grant. Results
      indicate that states' responses to the grant were to raise fewer tax dollars but
      still spend more by using federal funds. Significant substitution was found
      during the study period. Findings have implications for deliberations on grant
      structures for Medicaid and other federal/state programs.

PMID- 10961831
TI  - Hospital charges for colorectal cancer patients first admitted through an
      emergency department.
AB  - Some 11,023 colorectal cancer patients diagnosed in 1992-96 in Connecticut first
      were admitted to a hospital through a hospital emergency department. The average
      hospital inpatient charges and average length of stay were about 60 percent
      higher for emergency department versus nonemergency department first admissions.
      Emergency department status was an important predictor of charges independent of
      age at diagnosis and length of stay. Applying these data to the approximately
      131,000 colorectal cancers diagnosed in 1998 in the U.S., estimated excess
      hospital costs due to emergency department versus nonemergency department first
      admissions for colorectal cancer were about $328 million.

PMID- 10961832
TI  - Examining the existence of the underwriting cycle in managed care organizations.
AB  - This article examines the existence of the underwriting or profitability cycle in
      the health insurance industry. Researchers have reported that a six-year cycle
      exists for health care insurers. That is, three years of profits then are
      followed by three years of losses. This article suggests that insurers react more
      quickly to losses and adjust their cost structures almost immediately. Health
      insurers react to both expected changes and current increases in the payoff
      ratio.

PMID- 10961833
TI  - Valuation effects of health cost containment measures.
AB  - This study reports the findings of research into the valuation effects of health
      cost containment activities by publicly traded corporations. The motivation for
      this study was employers' increasing cost of providing health care insurance to
      their employees and employers' efforts to contain those costs. A 1990 survey of
      corporate health benefits indicated that these costs represented 25 percent of
      employers' net earnings and this would rise by the year 2000 if no actions were
      taken to reduce cost. Health cost containment programs that are implemented by
      firms should be seen by shareholders as a wealth maximizing effort. As such, this
      should be reflected in share price. This study employed standard event study
      methodology where the event is a media announcement or report regarding an
      attempt by a firm to contain the costs of providing health insurance and other
      health related benefits to employees. It examined abnormal returns on a number of
      event days and for a number of event intervals. Of the daily and interval returns
      that are least significant at the 10 percent level, virtually all are negative.
      Cross-sectional analysis shows that the abnormal returns are related negatively
      to a unionization variable.

PMID- 10961834
TI  - A longitudinal study of economies of scale in the hospital industry.
AB  - The Cobb-Douglas production function was used to empirically estimate whether or
      not larger hospitals have lower long-run average costs per bed than smaller
      hospitals. The results indicate that economies of scale have evolved recently for
      non-teaching and teaching hospitals. It is believed that the primary market
      forces that may be creating economies of scale in the hospital industry are
      decreasing revenues due to lower reimbursement and lower occupancy rates. As
      reimbursement and occupancy continue to trend down in the future, hospitals may
      seek additional economies to survive in an increasingly competitive and shrinking
      industry.

PMID- 10961835
TI  - Evidence for differential post-translational modifications of slow myosin heavy
      chain during murine skeletal muscle development.
AB  - The contractile properties of muscle fibres are, in part, determined by the
      myosin heavy chain (MyHC) isoforms they express. Using monoclonal antibodies, we
      show that at least three forms of slow twitch MyHC accumulate sequentially during
      mouse fetal development and that slow MyHC maturation in slow fibres occurs
      before expression of the adult fast MyHCs in fast fibres. Expression of deletion
      derivatives of beta-cardiac MyHC cDNA shows that the slow MyHC epitopes that are
      detected in adult but not in young animals are located near the N-terminus. The
      same N-terminal region of various fast MyHC molecules contains a conserved
      epitope that can, on occasions, be observed when slow MyHC cDNA is expressed in
      non-muscle cells. The results raise the possibility that the N-terminal epitopes
      result from post-translational modification of the MyHC and that a sequence of
      slow and fast MyHC isoform post-translational modifications plays a significant
      role during development of murine muscle fibres.

PMID- 10961837
TI  - Regulation of the rat sarcoplasmic reticulum calcium release channel by calcium.
AB  - The regulation by calcium of the ryanodine receptor/SR calcium release channel
      (RyR) from rat skeletal muscle was studied under isolated conditions and in situ.
      RyRs were either solubilized and incorporated into lipid bilayers or single
      fibres were mounted into a Vaseline gap voltage clamp. Single channel data were
      compared to parameters determined from the calculated calcium release flux. With
      K+ (250 mM) being the charge carrier the single channel conductance was 529 pS at
      50 microM Ca2+ cis and trans, and decreased with increasing cis [Ca2+]. Open
      probability showed a bell shaped calcium dependence revealing an activatory and
      an inhibitory Ca2+ binding site (Hill coefficients of 1.18 and 1.28,
      respectively) with half activatory and inhibitory concentrations of 9.4 and 298
      microM. The parameters of the inhibitory site agreed with the calcium dependence
      of channel inactivation deduced from the decline in SR calcium release in
      isolated fibres. Mean open time showed slight [Ca2+] dependence following a
      single exponential at every Ca2+ concentration tested. Closed time histograms, at
      high [Ca2+], were fitted with three exponentials, from which the longest was
      calcium independent, and resembled the recovery time constant of SR inactivation
      (115+/-15 ms) obtained in isolated fibres. The data are in agreement with a model
      where calcium binding to the inhibitory site on RyR would be responsible for the
      calcium dependent inactivation in situ.

PMID- 10961836
TI  - Actin and the smooth muscle regulatory proteins: a structural perspective.
AB  - The structural details of the smooth muscle acto-myosin interaction and its
      functional implications have been much discussed in recent years, however other,
      smooth muscle specific, actin-binding proteins have received much less attention.
      With increasing technical advances in structural biology a great deal of
      structural information is now coming to light, information that can provide
      useful insight into the mechanism of action for many important nonmotor actin
      binding proteins. The purpose of the review is to instill the current knowledge
      on the structure, and interaction sites on F-actin, of the major, non-motor actin
      binding proteins from smooth muscle, proposed to have a role in regulation. In
      the light of the recent structural studies the probable roles of the various
      actin-binding proteins will be discussed with particular reference to structure
      function relationships.

PMID- 10961838
TI  - Variable surface loops and myosin activity: accessories to a motor.
AB  - The catalytic head of myosin is a globular structure that has historically been
      divided into three segments of 25, 50, and 20 kDa. The solvent-exposed,
      proteolytically-sensitive surface loops of myosin that join these three segments
      are highly variable in their sequences. While surface loops have not
      traditionally been thought to affect enzymatic activities, these loops lie near
      the ATP and actin-binding sites and have been implicated in the modulation of
      myosin's kinetic activities. In this work we review the wealth of data regarding
      the loops that has accumulated over the years and discuss the roles of the loops
      in contributing to the different activities displayed by different myosin
      isoforms.

PMID- 10961839
TI  - Architecture of the thin filament-Z-line junction: lessons from nebulette and
      nebulin homologies.
AB  - Nebulette and nebulin are homologous proteins associated with the Z-lines of
      cardiac and skeletal muscle sarcomeres. Although these proteins share 70%
      sequence homology and an identical domain layout, nebulette is one-tenth the size
      of nebulin. To define structurally important features of these proteins in terms
      of the Z-line architecture, we have analyzed the primary structure of nebulette
      and nebulin from a variety of species and developmental stages. Alignment of the
      35 residue nebulin-like modules from both proteins demonstrates that the
      individual modules share 30-90% homology across the six proteins analyzed. In
      addition, this analysis demonstrates a number of areas in which the identity
      across the six proteins is as high as 75%. These areas may be important signals
      for Z-line assembly and function in the striated muscles. Significantly, most of
      the areas of high identity also coincide with consensus phosphorylation sites. To
      evaluate if nebulette, like nebulin, exhibits tissue-specific and developmental
      specific polymorphism, a series of immunoblot assays were performed. These data
      demonstrate that nebulettes from different portions of the heart are the same
      size. Comparison of nebulette from embryonic and adult cardiac muscle also
      demonstrates that this protein does not appear to vary in size with developmental
      stage. Consistent with the large number of consensus phosphorylation sites
      identified in the nebulette primary structure, we find that nebulette is
      phosphorylated in the cardiac muscle at serine and threonine residues. These data
      and sequence analyses are discussed in terms of current models for Z-line
      architecture.

PMID- 10961840
TI  - S-NO-actin: S-nitrosylation kinetics and the effect on isolated vascular smooth
      muscle.
AB  - We describe the modification of reactive actin sulfhydryls by S
      nitrosoglutathione. Kinetics of S-nitrosylation and denitrosylation suggest that
      only one cysteine of actin is involved in the reactions. By using the
      bifunctional sulfhydryl cross-linking reagent N,N'-1,4-phenylenebismaleimide and
      the monofunctional reagent N-iodoacetyl-N'-(5-sulpho-1-naphthyl)ethylenediamine,
      we identified this residue as Cys374. The time course of filament formation
      followed by high-shear viscosity changes revealed that S-nitrosylated G-actin
      polymerizes less efficiently than native monomers. The observed decrease in
      specific viscosity at steady state is due mainly to a marked inhibition of
      filament end-to-end annealing and, partially, to a reduction in F-actin
      concentration. Finally, S-nitrosylated actin acts as nitric oxide donor showing a
      fast, potent vasodilating activity at unusually low concentrations, being
      comparable with that of low molecular weight nitrosothiols.

PMID- 10961842
TI  - The Annual Meeting on Muscle Contraction and Cell Motility. Osaka, Japan, 6-8
      January 2000.

PMID- 10961841
TI  - The 5'-end of the porcine perinatal myosin heavy chain gene shows alternative
      splicing and is clustered with repeat elements.
AB  - The porcine perinatal myosin heavy chain (MyHC) is a major isoform in foetal
      skeletal muscles. We report here on its cDNA and genomic isolation, molecular
      characterisation and expression. Exon 2 and the first 4 bases of exon 3 of the
      perinatal MyHC gene. both part of the 5'-end untranslated region, showed
      differential splicing. About 2% of all perinatal MyHC transcripts of a 50-day-old
      foetus were without exon 2 and about half were without the 4 bases at the 5'-end
      of exon 3. Perinatal MyHC mRNA was expressed in all hind limb muscles of a 45-day
      old foetus along with the slow and embryonic MyHC isoforms in the same fibres.
      Unlike other sarcomeric MyHCs reported to date, the porcine perinatal promoter is
      clustered with repeat elements (4 SINEs and 1 microsatellite) and is without a
      consensus TATA box at the predicted site upstream of exon 1. Nonetheless, in
      reporter gene transfections, its promoter was found to be highly muscle-specific.
      The absence of a TATA box may point to a fundamental difference in the regulatory
      function between the perinatal and adult MyHC isoforms.

PMID- 10961843
TI  - James Desmond Smyth (1917-1999)--an appreciation.

PMID- 10961844
TI  - A survey of genes in Eimeria tenella merozoites by EST sequencing.
AB  - A study of about 500 expressed sequence tags (ESTs), derived from a merozoite
      cDNA library, was initiated as an approach to generate a larger pool of gene
      information on Eimeria tenella. Of the ESTs, 47.7% had matches with entries in
      the databases, including ribosomal proteins, metabolic enzymes and proteins with
      other functions, of which 14.3% represented previously known E. tenella genes.
      Thus over 50% of the ESTs had no significant database matches. The E. tenella EST
      dataset contained a range of highly abundant genes comparable with that found in
      the EST dataset of T. gondii and may thus reflect the importance of such
      molecules in the biology of the apicomplexan organisms. However, comparison of
      the two datasets revealed very few homologies between sequences of apical
      organelle molecules, and provides evidence for sequence divergence between these
      closely-related parasites. The data presented underpin the potential value of the
      EST strategy for the discovery of novel genes and may allow for a more rapid
      increase in the knowledge and understanding of gene expression in the merozoite
      life cycle stage of Eimeria spp.

PMID- 10961845
TI  - Differential recognition of Toxoplasma gondii recombinant nucleoside triphosphate
      hydrolase isoforms by naturally infected human sera.
AB  - Toxoplasma gondii possesses a highly active nucleoside triphosphate hydrolase,
      which has been shown to be an immunodominant antigen in mice and humans. Two
      isoforms (I and II) which exhibit different activities with respect to hydrolysis
      of ATP exist. Past studies suggest that all strains of T. gondii contain the less
      active nucleoside triphosphate hydrolase II, whilst only virulent strains contain
      the nucleoside triphosphate hydrolase I isoform. In order to further investigate
      the correlation between nucleoside triphosphate hydrolase isoform and biological
      significance, we cloned and expressed as glutathione S-transferase fusion
      proteins the full-length nucleoside triphosphate hydrolase I and II isoforms and
      two truncations of the nucleoside triphosphate hydrolase I isoform in Escherichia
      coli. We then used ELISAs with the full-length recombinant nucleoside
      triphosphate hydrolases as antigens to examine 188 naturally infected T. gondii
      positive sera and 83 T. gondii-negative sera for antibody reactivity. All
      positive sera reacted to T. gondii whole tachyzoite lysate antigen, 31 sera
      reacted to both nucleoside triphosphate hydrolase isoforms, three sera reacted
      specifically to nucleoside triphosphate hydrolase I and two sera reacted to only
      nucleoside triphosphate hydrolase II. Immunoblot analysis of the five sera
      reacting to either nucleoside triphosphate hydrolase I or II revealed both
      quantitative and qualitative differences in reactivity to the two isoforms.
      Comparative immunoblot analysis using the truncations of the nucleoside
      triphosphate hydrolase I isoform, and one of these positive sera identified a
      presumptive differential epitope between the nucleoside triphosphate hydrolase I
      and II isoforms within an 81 amino acid region (amino acids 445-526) at the C
      terminus of the nucleoside triphosphate hydrolase I isoform. This differential
      reactivity was further localised to the 12-residue region of greatest variability
      between the two isoforms (residues 488-499) using synthetic peptides. This is the
      first report where naturally infected human sera have been used to identify a
      differential epitope. Because this region is essential for substrate binding, an
      antibody response to this region may play some role in inhibition of this highly
      active enzyme.

PMID- 10961846
TI  - Elucidation of Schistosoma japonicum population dynamics in pigs using PCR-based
      identification of individuals representing distinct cohorts.
AB  - The study reported here investigated the interactions of successive infections
      and acquired resistance of pigs to challenge infections of Schistosoma japonicum.
      Two morphologically indistinguishable geographical isolates from China (from
      Anhui and Zhejiang provinces) were used for the infections. The worms of the two
      isolates were distinguishable by PCR-linked restriction fragment length
      polymorphism analysis of the nicotinamide adenine dinucleotide phosphate
      dehydrogenase I gene of the mitochondrial genome. Thirty-two pigs divided into
      seven groups were used in the experiment. Two groups received a single infection
      by either the Anhui or the Zhejiang isolate. In Challenge Groups 1, 4, 6, 8 and
      12, a primary infection of the Zhejiang isolate was followed by a challenge
      infection with the Anhui isolate at week 1, 4, 6, 8 or 12 after the primary
      infection. In this way it was possible to determine whether worms recovered by
      perfusion originated from the primary or the challenge infection. Only the
      challenge infection at week 1 resulted in a higher worm burden when compared with
      a single primary infection with the Zhejiang isolate. The results showed that
      challenge worms were able to establish, and that the proportion of worms
      originating from challenge infection increased at the later challenge infections,
      however without an increase in the total number of worms. In addition, mixed
      pairs of the two isolates were found in all challenge-infected groups. The
      results indicate that pigs are able to mount a partial resistance against re
      infection with S. japonicum by 4 weeks after a primary infection, but that worms
      of the challenge infections eventually replace the primary infection. The finding
      of mixed pairs of the two isolates indicates that worms of S. japonicum are
      either polygamous or able to wait in solitude for up to 12 weeks for a partner.

PMID- 10961847
TI  - Periodic appearance of a predominant variant antigen type during a chronic
      Giardia lamblia infection in a mouse model.
AB  - Giardia lamblia (syn. Giardia duodenalis, Giardia intestinalis) infections are
      associated with continuous antigenic variation of the parasite which is mediated
      by the parasite's major surface antigen, named variant surface protein. Offspring
      mice and corresponding mothers were infected with G. lamblia clone GS/M-83-H7
      (expressing variant surface protein H7) and various parameters of this infection
      were assessed in a long-term follow-up investigation. Our experimentation
      revealed that variant surface protein H7-type trophozoites were replaced by new
      variant-type trophozoites during the early stage of infection (around day 8
      p.i.), but the original variant-type re-emerged at at least two time-points
      during the later stages of infection (at days 22 and 42 p.i.). Such periods of
      variant surface protein H7-type trophozoite re-expansion were accompanied by
      transient production of intestinal IgA against variant-specific epitopes on a 314
      aa N-terminal region of variant surface protein H7. At late stages of infection
      (between days 42 and 200 p.i.), most mice produced intestinal IgA against both
      variant surface protein H7 and other antigens of the parasite. At these stages,
      infection seemed to be resolved in most mice, but occasional reappearance of
      relatively high (at day 64 p.i.) or at least detectable (at days 80 and 120 p.i.)
      amounts of intestinal parasites indicated that G. lamblia GS/M-83-H7 infections
      in mice may enter into a latent chronic phase which is interrupted by sporadic
      breakthroughs of parasite growth.

PMID- 10961849
TI  - Intraspecific and interspecific variation in the second internal transcribed
      spacer (ITS-2) sequence for Metastrongylus (Nematoda: Metastrongyloidea) detected
      by high resolution PCR-RFLP.
AB  - Metastrongylus species are important parasites of free-range pigs and wild boar,
      but little is known about the genetic make-up of natural populations. This study
      was undertaken to examine sequence variation in the internal transcribed spacer 2
      of ribosomal DNA within and among three species of Metastrongylus using PCR
      linked restriction fragment length polymorphism analysis. In contrast to many
      other species of bursate nematodes, significant intraspecific variation was
      detected in restriction fragment length polymorphism profiles among individual
      worms. In spite of this, it was possible to identify the three species by their
      distinctive restriction profiles. The findings suggest that the internal
      transcribed spacer 2 region should be useful for analysing population variation
      within Metastrongylus species.

PMID- 10961848
TI  - Identification and characterisation of three antigenic proteins from
      Cryptosporidium parvum sporozoites using a DNA library expressing poly-histidine
      tagged peptides.
AB  - To identify antigenic peptides of the parasite Cryptosporidium parvum, an
      expression library that allows for the production of chimeric proteins fused with
      a 6-histidine tag was made. The library was screened with C. parvum sporozoite
      rabbit anti-serum, and three positive clones (sa20, sa35, and sa40) were
      identified. The corresponding recombinant proteins (SA20, SA35, and SA40) were
      expressed in Escherichia coli and purified by metal-affinity chromatography. The
      sequence of sa20 and sa35 clones did not show any homology with known genes or
      proteins, whereas the 5' end of the sa40 clone showed homology with two
      previously identified C. parvum sequences. Hybridisations to intact chromosomes
      fractionated by pulsed-field gel electrophoresis revealed that the sa35 and sa40
      sequences are localised on chromosome VII, whereas the sa20 sequence is localised
      on chromosome VI. Reverse transcriptase-PCR experiments showed the presence of
      mRNAs for sa35 and sa40 in the oocyst, whereas the sa20 mRNA was undetectable in
      this stage. The serological response to the three proteins was assayed in C.
      parvum-immunised rabbits and in immunocompetent individuals with
      cryptosporidiosis. The Western blot results indicated that rabbits, challenged
      with a sporozoite crude antigen or with an oocyst crude antigen, were highly
      responsive to these three antigens. Human serum samples showed a response to the
      three proteins, although the response to SA20 appeared to be unrelated to a
      recent C. parvum infection. These results suggest that the SA35 and the SA40
      proteins may be useful in detecting C. parvum infections.

PMID- 10961850
TI  - Characterisation of the beta-tubulin gene of Cylicocyclus nassatus?
AB  - mRNA and genomic DNA were isolated from adult Cylicocyclus nassatus, and the mRNA
      was reverse transcribed. The cDNA was PCR amplified using degenerate primers
      designed according to the alignment of the beta-tubulin amino acid sequences of
      other species. To complete the coding sequence, the 3' end was amplified with the
      3' RACE, and for amplification of the 5' end the SL1-primer was used. The cDNA of
      the beta-tubulin gene of C. nassatus spans 1429 bp and encodes a protein of 448
      amino acids. Specific primers were developed from the cDNA sequence to amplify
      the genomic DNA sequence and to analyse the genomic organisation of the beta
      tubulin gene. The complete sequence of the genomic DNA of the beta-tubulin gene
      of C. nassatus has a size of 2652 bp and is organised into nine exons and eight
      introns. The identities with the exons of the gru-1 beta-tubulin gene of
      Haemonchus contortus range between 79% and 97%.

PMID- 10961851
TI  - Secondary structure model for the ITS-2 precursor rRNA of strongyloid nematodes
      of equids: implications for phylogenetic inference.
AB  - In order to maximise the positional homology in the primary sequence alignment of
      the second internal transcribed spacer for 30 species of equine strongyloid
      nematodes, the secondary structures of the precursor ribosomal RNA were predicted
      using an approach combining an energy minimisation method and comparative
      sequence analysis. The results indicated that a common secondary structure model
      of the second internal transcribed spacer of these nematodes was maintained
      despite significant interspecific differences (2-56%) in primary sequences. The
      secondary structure model was then used to refine the primary second internal
      transcribed spacer sequence alignment. The 'manual' and 'structure' alignments
      were both subjected to phylogenetic analysis to compare the effect of using
      different sequence alignments on phylogenetic inference. The topologies of the
      phylogenetic trees inferred from the manual second internal transcribed spacer
      alignment were usually different to those derived from the structure second
      internal transcribed spacer alignment. The results suggested that the positional
      homology in the second internal transcribed spacer primary sequence alignment was
      maximised when the secondary structure model was taken into consideration.

PMID- 10961853
TI  - Sequence differences in the internal transcribed spacers of DNA among four
      species of hookworm (Ancylostomatoidea: Ancylostoma).
AB  - The two ribosomal DNA internal transcribed spacers (1 and 2) of the hookworms
      Ancylostoma caninum, A. tubaeforme, A. ceylanicum and A. duodenale were
      sequenced. The sequence lengths were similar among the four species, except that
      A. ceylanicum had slightly longer (by 5-7 bp) internal transcribed spacer 1 and 2
      sequences. The predicted secondary structure of the internal transcribed spacer 2
      precursor rRNA was similar for all species, despite interspecific differences in
      primary sequence ranging from 0.9% to 13.2%. Interspecific differences in
      internal transcribed spacer 1 sequence ranged from 0.9% to 7.5%. A cladistic
      analysis of the sequence data, using the human hookworm Necator americanus as the
      outgroup, provided little resolution of the phylogenetic relationships, except
      that A. ceylanicum occurred on a branch external to the other three species.
      Nonetheless, internal transcribed spacers 1 and 2 may provide useful phylogenetic
      information at higher taxonomic levels within the superfamily Ancylostomatoidea.

PMID- 10961852
TI  - NADH dehydrogenase subunit 1 and cytochrome c oxidase subunit I sequences
      compared for members of the genus Taenia (Cestoda).
AB  - Nine members of the genus Taenia (Taenia taeniaeformis, Taenia hydatigena, Taenia
      pisiformis, Taenia ovis, Taenia multiceps, Taenia serialis, Taenia saginata,
      Taenia solium and the Asian Taenia) were characterised by their mitochondrial
      NADH dehydrogenase subunit 1 gene sequences and their genetic relationships were
      compared with those derived from the cytochrome c oxidase subunit 1 sequence
      data. The extent of inter-taxon sequence difference in NADH dehydrogenase subunit
      1 (approximately 5.9-30.8%) was usually greater than in cytochrome c oxidase
      subunit 1 (approximately 2.5-18%). Although topology of the phenograms derived
      from NADH dehydrogenase subunit 1 and cytochrome c oxidase subunit 1 sequence
      data differed, there was concordance in that T. multiceps, T. serialis (of
      canids), T. saginata and the Asian Taenia (of humans) were genetically most
      similar, and those four members were genetically more similar to T. ovis and T.
      solium than they were to T. hydatigena and T. pisiformis (of canids) or T.
      taeniaeformis (of cats). The NADH dehydrogenase subunit 1 sequence data may prove
      useful in studies of the systematics and population genetic structure of the
      Taeniidae.

PMID- 10961854
TI  - A hybridisation technique to identify anthelmintic resistance genes in
      Haemonchus.
AB  - The identification of genes associated with anthelmintic resistance can be
      facilitated in Haemonchus contortus by the ability of this species to hybridise
      with Haemonchus placei. Although the hybrid males are sterile, the lines can be
      rescued by backcrossing the females to either parental species. Resistance genes
      can be retained in Haemonchus hybrids, while the unwanted contortus background is
      removed through backcrossing to H. placei and anthelmintic selection of the
      progeny. Under this selection, genes involved in resistance would retain the H.
      contortus nucleotide sequence, while those that are not would either be H. placei
      or a random mixture of both, depending on the amount of backcrossing that had
      occurred. The first candidate gene to be tested in this system was a Haemonchus P
      glycoprotein, hcpgp-1. hcpgp-1 was amplified, cloned and sequenced from H.
      contortus and H. placei. Two restriction sites were then identified in the
      sequenced product; one specific to H. contortus hcpgp-1 and the other found only
      in the H. placei gene. These genes were identified from macrocyclic lactone
      selected and non-selected worms by restricting PCR products from individual
      worms. Fitted occurrence of the H. contortus allele was 49% of unselected worms
      and 69% of macrocyclic lactone selected worms. The probability of this percentage
      occurring by chance was P = 0.006. Thus macrocyclic lactone selection was acting
      to increase the percentage of hcpgp-1 from macrocyclic-lactone-resistant CAVRS.

PMID- 10961855
TI  - Human nakedness: adaptation against ectoparasites?
AB  - Homo sapiens L. has been described as the naked ape, and this nakedness
      undoubtedly constitutes one of the most striking differences in appearance
      between man and the apes. Nakedness has been attributed at various times to
      sexual selection [1], aquatic stage [2], hunting [3], cooling [4], sex [5],
      neoteny [6] and allometry [7], most proposed explanations logically revealing
      some aspect of the phenomenon. However, most fail to account for the
      distinctiveness of man's hairlessness among mammals of the same size.
      Unfortunately, fossils cannot help us to explain how denudation occurred, and how
      it helped hominids to survive. In this paper I will present an old hypothesis
      with a new point of view incorporating more recent evidence.

PMID- 10961856
TI  - Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required
      for functional activity.
AB  - Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with
      eight complementation groups. Four of the FA genes have been cloned, and at least
      three of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a
      nuclear complex, required for the maintenance of normal chromosome stability. In
      the current study, mutant forms of the FANCA and FANCG proteins have been
      generated and analyzed with respect to protein complex formation, nuclear
      translocation, and functional activity. The results demonstrate that the amino
      terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino
      terminal nuclear localization signal (NLS) of the FANCA protein. On the basis of
      2-hybrid analysis, the FANCA/FANCG binding is a direct protein-protein
      interaction. Interestingly, a truncated mutant form of the FANCG protein, lacking
      the carboxy terminus, binds in a complex with FANCA and translocates to the
      nucleus; however, this mutant protein fails to bind to FANCC and fails to correct
      the mitomycin C sensitivity of an FA-G cell line. Taken together, these results
      demonstrate that binding of FANCG to the amino terminal FANCA NLS sequence is
      necessary but not sufficient for the functional activity of FANCG. Additional
      amino acid sequences at the carboxy terminus of FANCG are required for the
      binding of FANCC in the complex. (Blood. 2000;96:1625-1632)

PMID- 10961857
TI  - Langerhans cells develop from a lymphoid-committed precursor.
AB  - Langerhans cells (LCs) are specialized dendritic cells (DCs) strategically
      located in stratified epithelia, such as those of the skin, oral cavity, pharynx,
      esophagus, upper airways, urethra, and female reproductive tract, which are
      exposed to a wide variety of microbial pathogens. LCs play an essential role in
      the induction of T-lymphocyte responses against viruses, bacteria, and parasites
      that gain access to those epithelial surfaces, due to their high antigen capture
      and processing potential and their capacity to present antigen peptides to T
      cells on migration to the lymph nodes.(1) Although LCs have been classically
      considered of myeloid origin, recent reports, which demonstrate the existence of
      lymphoid DCs derived from multipotent lymphoid precursors devoid of myeloid
      differentiation potential,(2-5) raise the question of the lymphoid or myeloid
      origin of LCs. The present study shows that mouse lymphoid-committed CD4(low)
      precursors, with the capacity to generate T cells, B cells, CD8(+) lymphoid DCs,
      and natural killer cells,(26) also generate epidermal LCs on intravenous
      transfer, supporting the view that LCs belong to the lymphoid lineage. (Blood.
      2000;96:1633-1637)

PMID- 10961858
TI  - Multiple nonfunctional alleles of CCR5 are frequent in various human populations.
AB  - CCR5 is the major coreceptor for macrophage-tropic strains of the human
      immunodeficiency virus type I (HIV-1). Homozygotes for a 32-base pair (bp)
      deletion in the coding sequence of the receptor (CCR5Delta32) were found to be
      highly resistant to viral infection, and CCR5 became, therefore, one of the
      paradigms illustrating the influence of genetic variability onto individual
      susceptibility to infectious and other diseases. We investigated the functional
      consequences of 16 other natural CCR5 mutations described in various human
      populations. We found that 10 of these variants are efficiently expressed at the
      cell surface, bind [(125)I]-MIP-1beta with affinities similar to wtCCR5, respond
      functionally to chemokines, and act as HIV-1 coreceptors. In addition to Delta32,
      six mutations were characterized by major alterations in their functional
      response to chemokines, as a consequence of intracellular trapping and poor
      expression at the cell surface (C101X, FS299), general or specific alteration of
      ligand binding affinities (C20S, C178R, A29S), or relative inability to mediate
      receptor activation (L55Q). A29S displayed an unusual pharmacological profile,
      binding and responding to MCP-2 similarly to wtCCR5, but exhibiting severely
      impaired binding and functional responses to MIP-1alpha, MIP-1beta, and RANTES.
      In addition to Delta32, only C101X was totally unable to mediate entry of HIV-1.
      The fact that nonfunctional CCR5 alleles are relatively frequent in various human
      populations reinforces the hypothesis of a selective pressure favoring these
      alleles. (Blood. 2000;96:1638-1645)

PMID- 10961860
TI  - Targeting the Ras signaling pathway: a rational, mechanism-based treatment for
      hematologic malignancies?
AB  - A series of alterations in the cellular genome affecting the expression or
      function of genes controlling cell growth and differentiation is considered to be
      the main cause of cancer. These mutational events include activation of oncogenes
      and inactivation of tumor suppressor genes. The elucidation of human cancer at
      the molecular level allows the design of rational, mechanism-based therapeutic
      agents that antagonize the specific activity of biochemical processes that are
      essential to the malignant phenotype of cancer cells. Because the frequency of
      RAS mutations is among the highest for any gene in human cancers, development of
      inhibitors of the Ras-mitogen-activated protein kinase pathway as potential
      anticancer agents is a very promising pharmacologic strategy. Inhibitors of Ras
      signaling have been shown to revert Ras-dependent transformation and cause
      regression of Ras-dependent tumors in animal models. The most promising new class
      of these potential cancer therapeutics are the farnesyltransferase inhibitors.
      The development of these compounds has been driven by the observation that
      oncogenic Ras function is dependent upon posttranslational modification, which
      enables membrane binding. In contrast to many conventional chemotherapeutics,
      farnesyltransferase inhibitors are remarkably specific and have been demonstrated
      to cause no gross systemic toxicity in animals. Some orally bioavailable
      inhibitors are presently being evaluated in phase II clinical trials. This review
      presents an overview on some inhibitors of the Ras signaling pathway, including
      their specificity and effectiveness in vivo. Because Ras signaling plays a
      crucial role in the pathogenesis of some hematologic malignancies, the potential
      therapeutic usefulness of these inhibitors is discussed. (Blood. 2000;96:1655
      1669)

PMID- 10961859
TI  - Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is
      associated with a human phagocyte immunodeficiency.
AB  - Rho GTPases control a variety of cellular processes, including actin
      polymerization, integrin complex formation, cell adhesion, gene transcription,
      cell cycle progression, and cell proliferation. A patient is described who has
      recurrent infections and defective neutrophil cellular functions similar to those
      found in Rac2-deficient mice. Molecular methods were used to clone the expressed
      Rac2 cDNA from this patient, and a single base pair change (G-->A at nucleotide
      169) in the coding sequence was identified. This results in an asparagine for
      aspartic acid mutation at amino acid 57 (D57N), a residue that is involved in
      nucleotide binding and is conserved in all mammalian Rho GTPases. The cloned cDNA
      was then introduced into normal bone marrow cells through retrovirus vectors, and
      neutrophils expressing this mutant exhibited decreased cell movement and
      production of superoxide in response to fMLP. The expressed recombinant protein
      was also analyzed biochemically and exhibited defective binding to GTP.
      Functional studies demonstrated that the D57N mutant behaves in a dominant
      negative fashion at the cellular level. The syndrome of Rac2 dysfunction
      represents a human condition associated with mutation of a Rho GTPase and is
      another example of human disease associated with abnormalities of small G protein
      signaling pathways. (Blood. 2000;96:1646-1654)

PMID- 10961861
TI  - How I treat older patients with AML.

PMID- 10961862
TI  - Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a
      most efficient monocyte attractant and CCR1 agonist.
AB  - Chemokines are proinflammatory cytokines that play a role in leukocyte migration
      and activation. Recent reports showed that RANTES (regulated on activation normal
      T-cell expressed and secreted chemokine), eotaxin, macrophage-derived chemokine
      (MDC), and stromal cell-derived factor-1 (SDF-1) are NH(2)-terminally truncated
      by the lymphocyte surface glycoprotein and protease CD26/dipeptidyl peptidase IV
      (CD26/DPP IV). Removal of the NH(2)-terminal dipeptide resulted in impaired
      inflammatory properties of RANTES, eotaxin, MDC, and SDF-1. The potential
      CD26/DPP IV substrate macrophage inflammatory protein-1beta (MIP-1beta) and the
      related chemokine, LD78alpha (ie, one of the MIP-1alpha isoforms), were not
      affected by this protease. However, CD26/DPP IV cleaved LD78beta, a most potent
      CCR5 binding chemokine and inhibitor of macrophage tropic human immunodeficiency
      virus-1 (HIV-1) infection, into LD78beta(3-70). Naturally truncated LD78beta(3
      70), but not truncated MIP-1beta, was recovered as an abundant chemokine form
      from peripheral blood mononuclear cells. In contrast to all other chemokines
      processed by CD26/DPP IV, LD78beta(3-70) had increased chemotactic activity in
      comparison to intact LD78beta. With a minimal effective concentration of 30
      pmol/L, LD78beta(3-70) became the most efficient monocyte chemoattractant.
      LD78beta(3-70) retained its high capacity to induce an intracellular calcium
      increase in CCR5-transfected cells. Moreover, on CCR1 transfectants, truncated
      LD78beta(3-70) was 30-fold more potent than intact LD78beta. Thus, CD26/DPP IV
      can exert not only a negative but also a positive feedback during inflammation by
      increasing the specific activity of LD78beta. CD26/DPP IV-cleaved LD78beta(3-70)
      is the most potent CCR1 and CCR5 agonist that retains strong anti-HIV-1 activity,
      indicating the importance of the chemokine-protease interaction in normal and
      pathologic conditions. (Blood. 2000;96:1674-1680)

PMID- 10961863
TI  - Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for
      chemokines (DARC).
AB  - Duffy antigen/receptor for chemokines (DARC) is a promiscuous receptor for
      chemokines that is required for Plasmodium vivax infection of erythroid cells.
      This receptor is expressed by subsets of endothelial, as well as erythroid cells.
      Selection for protection from malaria infection resulted in an erythroid-specific
      defect, suggesting that DARC may play a critical role in endothelial biology.
      Mice with targeted disruption of this gene were generated, and the function of
      DARC in inflammation was explored. RNA from spleens of homozygous mutant mice
      lacked DARC transcripts, which were abundant in wild-type (+/+) and heterozygote
      (+/-) mice. DARC(-/-) mice lacked developmental abnormalities and were healthy at
      1 year. Whereas hematologic parameters were within normal ranges, erythrocytes
      from nullizygous mice lacked CXC and CC chemokine-binding activity. Challenge
      with lipopolysaccharide resulted in significantly increased inflammatory
      infiltrates in lung and liver of nullizygous mice. These results suggest that
      DARC modulates the intensity of inflammatory reactions as a sink for chemokines.
      (Blood. 2000;96:1681-1684)

PMID- 10961864
TI  - Effect of active prenatal management on pregnancy outcome in sickle cell disease
      in an African setting.
AB  - Sickle cell disease (SCD) is associated with an increased risk of medical
      complications during pregnancy. In sub-Saharan Africa, fetal and maternal
      mortality rates are particularly high. This study evaluated the effect of an
      active prenatal management program on pregnancy outcome in patients with SCD in
      an African setting. Pregnant women with SCD attending the National Teaching
      Hospital in Cotonou (The Republic of Benin, West Africa) were recruited before
      the 28th week of gestation. Management was based on providing information and
      education about SCD and improving nutritional status, malaria prevention, early
      detection of bacterial infections, and restricted use of blood transfusion.
      Maternal and fetal mortality rates and SCD-related morbidity were the principal
      variables assessed. One hundred and eight patients (42 SS and 66 SC) with 111
      fetuses were included in the study. Thirteen fetal deaths (from 9 SS and 4 SC
      mothers) were recorded and 2 deaths of SC mothers. The maternal mortality rate of
      1.8% was comparable with the overall maternal mortality rate for this maternity
      unit (1.2%). Few SCD-related events were recorded. Plasmodium falciparum malaria
      infection was the major cause of morbidity. Sixty-three patients (19 SS and 44
      SC) successfully completed their pregnancy (58.3%) without requiring transfusion.
      Providing pregnant SCD patients with relevant medical care based on simple cost
      effective approaches can have a positive impact on SCD-associated morbidity and
      mortality in an otherwise difficult setting in Africa. (Blood. 2000;96:1685-1689)

PMID- 10961865
TI  - Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus
      host disease prophylaxis in patients with severe aplastic anemia given allogeneic
      bone marrow transplantation from an HLA-identical sibling: results of a
      GITMO/EBMT randomized trial.
AB  - A randomized trial was carried out comparing cyclosporin A (CsA) and short-term
      methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD)
      prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic
      bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients
      (median age, 19 years; range, 4-46 years) were randomized to receive either CsA
      and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups
      received CsA orally, with gradual drug reduction until discontinuation 8 to 12
      months after BMT. Patients randomized in both arms had comparable characteristics
      and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4
      days). The median time for neutrophil engraftment was 17 days (range, 11-31 days)
      and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA
      alone group, respectively (P =.01). No significant difference was observed in the
      probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD
      developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation
      related mortality rates for patients given either CsA/MTX or CsA alone were 3%
      and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT,
      the 5-year survival probability is 94% for patients in the CsA/MTX group and 78%
      for those in the CsA alone group (P =. 05). These data indicate that the use of
      CsA with MTX is associated with improved survival in patients with SAA who
      receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)

PMID- 10961866
TI  - Immune tolerance induction in hemophilia patients with inhibitors: costly can be
      cheaper.
AB  - The development of inhibitory antibodies to factor VIII (FVIII) occurs in
      approximately 30% to 40% of patients with severe hemophilia A. Management options
      for patients with inhibitor include eradicating it via immune tolerance induction
      (ITI) or treating bleeding episodes with large quantities of hemostatic agents.
      ITI is costly, approaching $1 million for the average 5-year-old, but if
      successful results in improved clinical outcomes. We constructed a decision
      analysis using the Markov process to model expected clinical outcomes and costs
      over a lifetime for a typical 5-year-old hemophiliac with high inhibitor levels.
      Estimates of relevant variables were based on a thorough review of the medical
      literature. Outcomes modeled included total lifetime costs as well as life
      expectancy. The decision analytic model revealed that the ITI strategy was
      associated with an increase in projected life expectancy of 4.6 years. Total
      estimated lifetime costs for the ITI strategy were approximately $1.7 million
      less per patient. Sensitivity analyses over clinically and economically
      reasonable ranges did not change these findings. The insight that ITI can achieve
      an improved clinical outcome while being cost-saving is not reflected in many
      current treatment regimens. This example also illustrates that expensive therapy
      for patients with a chronic disease may be cost effective when analyzed from a
      societal perspective over the patient's lifetime. This finding has important
      policy implications for medical decision makers at many levels and reinforces the
      need to undertake pharmacoeconomic analyses and choose therapies from a long
      term, societal perspective. (Blood. 2000;96:1698-1702)

PMID- 10961867
TI  - Impact of the patient population on the risk for heparin-induced
      thrombocytopenia.
AB  - The frequency of immune heparin-induced thrombocytopenia (HIT) varies among
      prospective studies. It is unknown whether this is caused by differences in the
      heparin preparations, the patient populations, or the types of serologic assay
      used to confirm the diagnosis. Seven hundred forty-four patients were studied
      from 3 different clinical treatment settings, as follows: unfractionated heparin
      (UFH) during or after cardiac surgery (n = 100), UFH after orthopedic surgery (n
      = 205), and low-molecular-weight heparin (LMWH) after orthopedic surgery (n =
      439). Both an activation assay and an antigen assay were used to detect heparin
      dependent IgG (HIT-IgG) antibodies. By activation assay, the frequency of HIT-IgG
      formation ranged from a low of 3.2% in orthopedic patients receiving LMWH to a
      high of 20% in cardiac patients receiving UFH; by antigen assay, the
      corresponding frequencies ranged from 7.5% to 50%. Both UFH use (P =.002) and
      cardiac surgery (P =.01) were more likely to be associated with HIT-IgG
      formation. However, among patients in whom HIT-IgG formed and who were
      administered UFH, the probability for HIT was higher among orthopedic patients
      than among cardiac patients (by activation assay: 52.6% compared with 5%; odds
      ratio, 21.1 [95% CI, 2.2-962.8]; P =.001; by antigen assay: 34.5% compared with
      2.0%; odds ratio, 25.8 [95% CI, 3.2-1141]; P <.001). It is concluded that there
      is an unexpected dissociation between the frequency of HIT-IgG formation and the
      risk for HIT that is dependent on the patient population. HIT-IgG antibodies are
      more likely to form in patients who undergo cardiac surgery than in orthopedic
      patients, but among patients in whom antibodies do form, orthopedic patients are
      more likely to develop HIT. (Blood. 2000;96:1703-1708)

PMID- 10961868
TI  - Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly
      dosing produces superior induction remission rates in childhood relapsed acute
      lymphoblastic leukemia: a Pediatric Oncology Group Study.
AB  - The relapse rate in childhood acute lymphoblastic leukemia (ALL) is approximately
      30% but few reinduction regimens have investigated the intensive use of
      polyethylene glycol Escherichia coli asparaginase (PEG-Asp). Therefore, we
      assessed the pharmocokinetics and efficacy of PEG-Asp in this setting. Children
      with B-precursor ALL, in first marrow and/or extramedullary relapse were
      eligible. Reinduction included doxorubicin on day 1, prednisone for 28 days,
      vincristine weekly for 4 weeks, and PEG-Asp either weekly or biweekly by
      randomization. Asparaginase levels and antibody to both E coli asparaginase and
      PEG-asp were measured weekly just before each PEG-asp dose. Overall, 129 of 144
      patients (pts) (90%) achieved a complete remission (CR). There was a highly
      significant difference in CR rates between weekly (69 of 71; 97%) and biweekly
      (60 of 73; 82%) PEG-Asp dosing (P =.003). Grade 3 or 4 infectious toxicity was
      common (50%), but only 4 pts died of sepsis during induction. Other toxicities
      were infrequent and hypersensitivity was rare (6 of 144; 4%). Low asparaginase
      levels were associated with high antibody titers to either native (P =.024) or
      PEG asp (P =.0013). The CR rate was significantly associated with higher levels
      of asparaginase (P =. 012). Patients with ALL in first relapse receiving weekly
      PEG-Asp had a higher rate of second remission compared with biweekly dosing. Low
      levels of asparaginase were associated with high antibody titers. Increased
      asparaginase levels may correlate with an improved CR rate. The use of intensive
      PEG-Asp should be explored further in the treatment of ALL. (Blood. 2000;96:1709
      1715)

PMID- 10961869
TI  - N(G)-monomethyl-L-arginine inhibits erythropoietin gene expression by stimulating
      GATA-2.
AB  - N(G)-monomethyl-L-arginine (L-NMMA) has been reported to be elevated in uremic
      patients. Based on the hypothesis that the pathogenesis of the anemia of renal
      disease might be due to the perturbation of transcription factors of the
      erythropoietin (Epo) gene by L-NMMA, the present study was designed to
      investigate the effect of L-NMMA on Epo gene expression through the GATA
      transcription factor. L-NMMA caused decreased levels of NO, cyclic guanosine
      monophosphate (cGMP), and Epo protein in Hep3B cells. L-NAME (analogue of L-NMMA)
      also inhibited Epo production in anemic mice. Transfection of the Epo promoter
      luciferase gene into Hep3B cells revealed that L-NMMA inhibited the Epo promoter
      activity. However, L-NMMA did not inhibit the Epo promoter activity when mutated
      Epo promoter (GATA to TATA) was transfected, and L-NMMA did not affect the
      enhancer activity. Electrophoretic mobility shift assays demonstrated the
      stimulation of GATA binding activity by L-NMMA. However, L-NMMA had no effect on
      the binding activity of hepatic nuclear factor-4, COUP-TF1, hypoxia-inducing
      factor-1, or NF-kappaB. Furthermore, cGMP inhibited the L-NMMA-induced GATA
      binding activity. L-NMMA also increased GATA-2 messenger RNA expression. These
      results demonstrate that L-NMMA suppresses Epo gene expression by up-regulation
      of the GATA transcription factor and support the hypothesis that L-NMMA is one of
      the candidate substances that underlie the pathogenesis of renal anemia. (Blood.
      2000;96:1716-1722)

PMID- 10961870
TI  - Adiponectin, a new member of the family of soluble defense collagens, negatively
      regulates the growth of myelomonocytic progenitors and the functions of
      macrophages.
AB  - We investigated the functions of adiponectin, an adipocyte-specific secretory
      protein and a new member of the family of soluble defense collagens, in
      hematopoiesis and immune responses. Adiponectin suppressed colony formation from
      colony-forming units (CFU)-granulocyte-macrophage, CFU-macrophage, and CFU
      granulocyte, whereas it had no effect on that of burst-forming units-erythroid or
      mixed erythroid-myeloid CFU. In addition, adiponectin inhibited proliferation of
      4 of 9 myeloid cell lines but did not suppress proliferation of erythroid or
      lymphoid cell lines except for one cell line. These results suggest that
      adiponectin predominantly inhibits proliferation of myelomonocytic lineage cells.
      At least one mechanism of the growth inhibition is induction of apoptosis because
      treatment of acute myelomonocytic leukemia lines with adiponectin induced the
      appearance of subdiploid peaks and oligonucleosomal DNA fragmentation. Aside from
      inhibiting growth of myelomonocytic progenitors, adiponectin suppressed mature
      macrophage functions. Treatment of cultured macrophages with adiponectin
      significantly inhibited their phagocytic activity and their lipopolysaccharide
      induced production of tumor necrosis factor alpha. Suppression of phagocytosis by
      adiponectin is mediated by one of the complement C1q receptors, C1qRp, because
      this function was completely abrogated by the addition of an anti-C1qRp
      monoclonal antibody. These observations suggest that adiponectin is an important
      negative regulator in hematopoiesis and immune systems and raise the possibility
      that it may be involved in ending inflammatory responses through its inhibitory
      functions. (Blood. 2000;96:1723-1732)

PMID- 10961871
TI  - Pyk2 and Syk participate in functional activation of granulocytic HL-60 cells in
      a different manner.
AB  - The roles of the protein tyrosine kinases Pyk2 (also called RAFTK or CAK beta)
      and Syk in the process of functional activation of human myeloid cells were
      examined. During granulocytic differentiation of HL-60 cells with dimethyl
      sulfoxide (DMSO), the amounts of Pyk2 and beta2 integrin increased, whereas the
      amount of Syk was abundant before differentiation and did not change during
      differentiation. When the granulocytic cells were stimulated with N-formyl-L
      methionyl-L-leucyl-L-phenylalanine (fMLP), tyrosine phosphorylation of Pyk2
      occurred promptly and subsequent association of Pyk2 with beta2 integrin was
      detected. In contrast, Syk was not tyrosine phosphorylated by fMLP stimulation
      but constitutively associated with beta2 integrin. Stimulation with fMLP also
      caused the alteration of beta2 integrin to an activated form, a finding that was
      confirmed by the observation of fMLP-induced cell attachment on fibrinogen-coated
      dishes and inhibition of this attachment by pretreatment with anti-beta2 integrin
      antibody. Cell attachment to fibrinogen caused the enhanced tyrosine
      phosphorylation of Pyk2 and the initial tyrosine phosphorylation of Syk, which
      was also inhibited by pretreatment with anti-beta2 integrin antibody. In vitro
      kinase assays revealed that Pyk2 and Syk represented kinase activities to induce
      tyrosine phosphorylation of several molecules in the anti-beta2 integrin
      immunoprecipitates of the attached cells. These results showed that Pyk2 is
      involved in the functional activation of granulocytic cells in 2 signaling
      pathways: an fMLP receptor-mediated "inside-out" signaling pathway that might
      cause beta2 integrin activation and a subsequent beta2 integrin-mediated "outside
      in" signaling pathway. Syk was activated in relation to cell attachment to
      fibrinogen as a result of "outside-in" signaling, although it was already
      associated with beta2 integrin before fMLP stimulation. (Blood. 2000;96:1733
      1739)

PMID- 10961872
TI  - Identification of novel circulating human embryonic blood stem cells.
AB  - Using murine models, primitive hematopoietic cells capable of repopulation have
      been shown to reside in various anatomic locations, including the aortic gonad
      mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded
      by stem cells migrating through fetal circulation and would serve as ideal
      targets for in utero cellular therapy. In humans, however, it is unknown whether
      similar stem cells exist. Here, we identify circulating hematopoeitic cells
      present during human in utero development that are capable of multilineage
      repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined
      immunodeficient) mice. Using limiting dilution analysis, the frequency of these
      fetal stem cells was found to be 1 in 3.2 x 10(5), illustrating a 3- and 22-fold
      enrichment compared with full-term human cord blood and circulating adult
      mobilized-peripheral blood, respectively. Comparison of in vivo differentiation
      and proliferative capacity demonstrated that circulating fetal stem cells are
      intrinsically distinct from hematopoietic stem cells found later in human
      development and those derived from the fetal liver or fetal bone marrow
      compartment at equivalent gestation. Taken together, these studies demonstrate
      the existence of unique circulating stem cells in early human embryonic
      development that provide a novel and previously unexplored source of pluripotent
      stem cell targets for cellular and gene-based fetal therapies. (Blood.
      2000;96:1740-1747)

PMID- 10961873
TI  - Interleukin-3 supports expansion of long-term multilineage repopulating activity
      after multiple stem cell divisions in vitro.
AB  - Although long-term repopulating hematopoietic stem cells (HSC) can self-renew and
      expand extensively in vivo, most efforts at expanding HSC in vitro have proved
      unsuccessful and have frequently resulted in compromised rather than improved HSC
      grafts. This has triggered the search for the optimal combination of cytokines
      for HSC expansion. Through such studies, c-kit ligand (KL), flt3 ligand (FL),
      thrombopoietin, and IL-11 have emerged as likely positive regulators of HSC self
      renewal. In contrast, numerous studies have implicated a unique and potent
      negative regulatory role of IL-3, suggesting perhaps distinct regulation of HSC
      fate by different cytokines. However, the interpretations of these findings are
      complicated by the fact that different cytokines might target distinct
      subpopulations within the HSC compartment and by the lack of evidence for HSC
      undergoing self-renewal. Here, in the presence of KL+FL+megakaryocyte growth and
      development factor (MGDF), which recruits virtually all Lin(-)Sca-1(+)kit(+) bone
      marrow cells into proliferation and promotes their self-renewal under serum-free
      conditions, IL-3 and IL-11 revealed an indistinguishable ability to further
      enhance proliferation. Surprisingly, and similar to IL-11, IL-3 supported
      KL+FL+MGDF-induced expansion of multilineage, long-term reconstituting activity
      in primary and secondary recipients. Furthermore, high-resolution cell division
      tracking demonstrated that all HSC underwent a minimum of 5 cell divisions,
      suggesting that long-term repopulating HSC are not compromised by IL-3
      stimulation after multiple cell divisions. In striking contrast, the ex vivo
      expansion of murine HSC in fetal calf serum-containing medium resulted in
      extensive loss of reconstituting activity, an effect further facilitated by the
      presence of IL-3. (Blood. 2000;96:1748-1755)

PMID- 10961874
TI  - Apoptosis is rapidly triggered by antisense depletion of MCL-1 in differentiating
      U937 cells.
AB  - Mcl-1 is a member of the Bcl-2 protein family, which has been shown to delay
      apoptosis in transfection and/or overexpression experiments. As yet no gene
      knockout mice have been engineered, and so there is little evidence to show that
      loss of Mcl-1 expression is sufficient to trigger apoptosis. U937 cells
      constitutively express the antiapoptotic protein Bcl-2; but during
      differentiation, in response to the phorbol ester PMA (phorbol 12 beta-myristate
      13 alpha-acetate), Mcl-1 is transiently induced. The purpose of this
      investigation was to determine the functional role played by Mcl-1 in this
      differentiation program. Mcl-1 expression was specifically disrupted by chimeric
      methylphosphonate/phosphodiester antisense oligodeoxynucleotides to just 5% of
      control levels. The depletion of Mcl-1 messenger RNA (mRNA) and protein was both
      rapid and specific, as indicated by the use of control oligodeoxynucleotides and
      analysis of the expression of other BCL2 family members and PMA-induced tumor
      necrosis factor-alpha (TNF-alpha). Specific depletion of Mcl-1 mRNA and protein,
      in the absence of changes in cellular levels of Bcl-2, results in a rapid entry
      into apoptosis. Levels of the proapoptotic protein Bax remained unchanged during
      differentiation, while Bak expression doubled within 24 hours. Apoptosis was
      detected within 4 hours of Mcl-1 antisense treatment by a variety of parameters
      including a novel live cell imaging technique allowing correlation of antisense
      treatment and apoptosis in individual cells. The induction of Mcl-1 is required
      to prevent apoptosis during differentiation of U937 cells, and the constitutive
      expression of Bcl-2 is unable to compensate for the loss of Mcl-1. (Blood.
      2000;96:1756-1763)

PMID- 10961875
TI  - Mcl-1 is a common target of stem cell factor and interleukin-5 for apoptosis
      prevention activity via MEK/MAPK and PI-3K/Akt pathways.
AB  - Stem cell factor (SCF) has been suggested as essential for optimal production of
      various hematopoietic lineages mainly because of its apoptosis prevention
      function when it costimulates with other cytokines. However, the underlying
      mechanism of this synergism of apoptosis prevention is largely unknown. The
      present study examined the expression of some Bcl-2 family members, including Bcl
      2, Bcl-X(L), Mcl-1, and Bax, in response to cytokine stimulation in TF-1 and JYTF
      1 cells in which SCF costimulation is differentially required for optimal
      proliferation. The results revealed that only the expression of Mcl-1 highly
      correlated with the antiapoptotic activity of interleukin-5 (IL-5) and the
      synergistic effect of SCF. In TF-1 cells, the defect of IL-5 in apoptosis
      suppression and Mcl-1 induction was associated with the incapability to highly
      phosphorylate Janus kinases (JAK1, JAK2), signal transducer and activator of
      transcription-5 (STAT5), mitogen-activated protein kinase (MAPK), and Akt/PKB,
      whereas SCF costimulation restored the potent phosphorylation of MAPK and
      Akt/PKB, but not STAT5. The importance of MAPK and Akt/PKB signaling pathways in
      regulating the expression of Mcl-1 and cell survival was further supported by the
      observation that inhibition of MEK by PD98059 or phosphatidylinositol-3 kinase
      (PI-3K) by LY294002 independently resulted in the reduction of Mcl-1 expression
      and loss of cell viability. Therefore, the data suggest that Mcl-1 is a common
      antiapoptotic target of both early-stage cytokine SCF and late-stage cytokine IL
      5. Both MEK/MAPK and PI-3K/Akt signaling pathways are essential in the regulation
      of Mcl-1 expression and apoptosis prevention. (Blood. 2000;96:1764-1771)

PMID- 10961876
TI  - Egr-1 gene is induced by the systemic administration of the vascular endothelial
      growth factor and the epidermal growth factor.
AB  - Egr-1 is a transcription factor that couples short-term changes in the
      extracellular milieu to long-term changes in gene expression. In cultured
      endothelial cells, the Egr-1 gene has been shown to respond to a variety of
      extracellular signals. However, the physiological relevance of these findings
      remains unclear. To address this question, the growth factor-mediated response of
      the Egr-1 gene under in vivo conditions was analyzed. To that end, either
      vascular endothelial growth factor (VEGF) or epidermal growth factor (EGF) was
      injected into the intraperitoneal cavity of mice. Growth factors were delivered
      to all tissues examined, as evidenced by the widespread distribution of I(125)
      labeled growth factors and the phosphorylation of their respective receptors. In
      Western blot analyses of whole-tissue extracts, Egr-1 protein levels were shown
      to be induced in the heart, brain, liver, and spleen of VEGF-treated mice, and in
      the heart, lung, brain, liver and skeletal muscle of EGF-treated animals. Changes
      in Egr-1 levels did not correlate with changes in receptor phosphorylation or
      ERK1/2 phosphorylation. In Northern blot analyses, VEGF induced Egr-1 mRNA levels
      in all tissues examined except lung and kidney, whereas EGF led to increased
      transcripts in all tissues except kidney. In immunofluorescence studies, VEGF
      induced Egr-1 in microvascular endothelial cells of the heart and liver, and EGF
      induced Egr-1 in the microvascular bed of skeletal muscle. Taken together, these
      results suggest that the Egr-1 gene is differentially regulated in response to
      systemically administered VEGF and EGF. (Blood. 2000;96:1772-1781)

PMID- 10961877
TI  - Molecular mechanisms of platelet exocytosis: role of SNAP-23 and syntaxin 2 and 4
      in lysosome release.
AB  - On stimulation by strong agonists, platelets release the contents of 3 storage
      compartments in 2 apparent waves of exocytosis. The first wave is the release of
      alpha- and dense core granule contents and the second is the release of lysosomal
      contents. Using a streptolysin O-permeabilized platelet exocytosis assay, we show
      that hexosaminidase release is stimulated by either Ca(++) or by GTP-gamma-S.
      This release step retains the same temporal separation from serotonin release as
      seen in intact platelets. This assay system was also used to dissect the
      molecular mechanisms of lysosome exocytosis. Lysosome release requires adenosine
      triphosphate and the general membrane fusion protein, N-ethylmaleimide sensitive
      factor. Uniquely, 2 syntaxin t-SNAREs, syntaxin 2 and 4, which localize to
      granules and open canalicular membranes, together with the general target
      membrane SNAP receptor (t-SNARE) protein SNAP-23 appear to make up the
      heterodimeric t-SNAREs required for lysosome exocytosis. These studies further
      show that regardless of stimuli (Ca(++) or GTP-gamma-S) serotonin and
      hexosaminidase release requires the same membrane fusion machinery. (Blood.
      2000;96:1782-1788)

PMID- 10961878
TI  - Immobilized platelets support human colon carcinoma cell tethering, rolling, and
      firm adhesion under dynamic flow conditions.
AB  - Accumulating evidence suggests that successful metastatic spread may depend on
      the ability of tumor cells to undergo extensive interactions with platelets.
      However, the mechanisms mediating tumor cell adhesion to platelets under
      conditions of flow remain largely unknown. Therefore, this study was designed to
      analyze the ability of 3 human colon carcinoma cell lines (LS174T, COLO205, and
      HCT-8) to bind to surface-anchored platelets under flow and to identify the
      receptors involved in these processes. Immobilized platelets support LS174T cell
      adhesion at wall shear stresses up to 1.4 dyn/cm(2). Our data suggest that
      platelets primarily recruit LS174T cells through a 2-step, sequential process of
      adhesive interactions that shares common features but is distinct from that
      elaborated for neutrophils. Platelet P-selectin mediates LS174T cell tethering
      and rolling in a PSGL-1- and CD24-independent manner. Moreover, platelet
      alpha(IIb)beta(3)-integrins appear to be capable of directly capturing LS174T
      cells from the fluid stream, and also convert instantaneously transient tethers
      initiated by P-selectin into stable adhesion. This step is at least partially
      mediated by von Willebrand factor, but not fibrinogen or fibronectin, that
      bridges platelet alpha(IIb)beta(3) with a yet unidentified receptor on the LS174T
      cell surface via an RGD-dependent mechanism. The sequential engagement of
      platelet P-selectin and alpha(IIb)beta(3) is also requisite for the optimal
      adhesion of COLO205. Furthermore, HCT-8 cells, which fail to interact with P
      selectin, tether minimally to surface-anchored platelets under flow, despite
      their extensive adhesive interactions under static conditions. This cascade of
      events depicts an efficacious process for colon carcinoma arrest at sites of
      vascular injury. (Blood. 2000;96:1789-1797)

PMID- 10961879
TI  - Cloning, characterization, and functional studies of human and mouse glycoprotein
      VI: a platelet-specific collagen receptor from the immunoglobulin superfamily.
AB  - Injuries to the vessel wall and subsequent exposure of collagen from the
      subendothelial matrix result in thrombus formation. In physiological conditions,
      the platelet plug limits blood loss. However, in pathologic conditions, such as
      rupture of atherosclerotic plaques, platelet-collagen interactions are associated
      with cardiovascular and cerebral vascular diseases. Platelet glycoprotein VI
      (GPVI) plays a crucial role in collagen-induced activation and aggregation of
      platelets, and people who are deficient in GPVI suffer from bleeding disorders.
      Based on the fact that GPVI is coupled to the Fc receptor (FcR)-gamma chain and
      thus should share homology with the FcR chains, the genes encoding human and
      mouse GPVI were identified. They belong to the immunoglobulin (Ig) superfamily
      and share 64% homology at the protein level. Functional evidence demonstrating
      the identity of the recombinant protein with GPVI was shown by binding to its
      natural ligand collagen; binding to convulxin (Cvx), a GPVI-specific ligand from
      snake venom; binding of anti-GPVI IgG isolated from a patient; and association to
      the FcR-gamma chain. The study also demonstrated that the soluble protein blocks
      Cvx and collagen-induced platelet aggregation and that GPVI expression is
      restricted to megakaryocytes and platelets. Finally, human GPVI was mapped to
      chromosome 19, long arm, region 1, band 3 (19q13), in the same region as multiple
      members of the Ig superfamily. This work offers the opportunity to explore the
      involvement of GPVI in thrombotic disease, to develop alternative antithrombotic
      compounds, and to characterize the mechanism involved in GPVI genetic
      deficiencies. (Blood. 2000;96:1798-1807)

PMID- 10961880
TI  - von Willebrand factor storage and multimerization: 2 independent intracellular
      processes.
AB  - The von Willebrand factor propeptide, vW AgII, has been shown to be required for
      the formation of vWF multimers and sorting of vWF to storage granules; whether
      these 2 processes are independent events has been unclear. Chimeric constructs of
      human and canine vWF were developed to further define these processes and to
      determine whether they are independent intracellular events. Cells expressing
      only mature vWF (Deltapro) produced vWF dimers that were not stored in AtT-20
      cells; whereas the expression of vW AgII alone resulted in vW AgII granular
      storage. Expression of vW AgII in trans with Deltapro resulted in the
      multimerization of vWF and colocalized storage of vW AgII and vWF. Expression of
      canine vW AgII in trans or cis with human Deltapro resulted in the
      multimerization of human vWF, with no storage of human vWF but with normal
      storage of canine vW AgII. This dissociation of functions indicates that the
      signals for multimerization of vWF are different from the signals for trafficking
      of vWF to storage and demonstrates that vWF storage and multimerization are 2
      independent intracellular processes. vW AgII contains the signal(s) required for
      trafficking to storage, and only through interaction with vW AgII is vWF
      chaperoned into granules. (Blood. 2000;96:1808-1815)

PMID- 10961881
TI  - Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and
      risk of over-anticoagulation in patients on long-term treatment.
AB  - Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant
      effect of warfarin. Genetic polymorphisms in CYP2C9 producing variants with
      altered catalytic properties have been identified. Patients (n = 561) with a
      target international normalized ratio (INR) of 2.5 who had been treated with
      warfarin for more than 2 months were anonymously genotyped for the wild-type
      CYP2C9*1 allele and the 2C9*2 and 2C9*3 variants. The mean maintenance dose of
      warfarin in patients who were wild-type for both alleles was 5.01 mg. The
      maintenance dose of warfarin was significantly related to genotype (Kruskall
      Wallis, chi(2) = 17.985, P =.001) with mean maintenance doses in patients with
      variant alleles between 61% and 86% of that in wild-type patients. The odds ratio
      for the 2C9*2 allele in patients with a maintenance dose of 1. 5 mg or less was
      5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in
      patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD
      of the mean INR, percentage of high INRs, and person-time spent in range were
      determined as parameters of stability. There was no difference between patients
      grouped according to genotype for any parameter of stability. This study
      confirmed an association between CYP2C9 genotype and warfarin sensitivity.
      However, the possession of a variant allele does not increase the likelihood of
      severe over-anticoagulation or stability of anticoagulation during long-term
      therapy. (Blood. 2000;96:1816-1819)

PMID- 10961882
TI  - Urokinase mediates fibrinolysis in the pulmonary microvasculature.
AB  - The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in
      fibrinolysis remains unsettled. The contribution of uPA may depend on the
      vascular location, the physical properties of the clot, and its impact on tissue
      function. To study the contribution of urokinase within the pulmonary
      microvasculature, a model of pulmonary microembolism in the mouse was developed.
      Iodine 125 ((125)I)-labeled fibrin microparticles injected intravenously through
      the tail vein lodged preferentially in the lung, distributing homogeneously
      throughout the lobes. Clearance of (125)I-microemboli in wild type mice was rapid
      and essentially complete by 5 hours. In contrast, uPA(-/-) and tissue-type
      plasminogen activator tPA(-/-) mice, but not uPAR(-/-) mice, showed a marked
      impairment in pulmonary fibrinolysis throughout the experimental period. The
      phenotype in the uPA(-/-) mouse was rescued completely by infusion of single
      chain uPA (scuPA). The increment in clot lysis was 4-fold greater in uPA(-/-)
      mice infused with the same concentration of scuPA complexed with soluble
      recombinant uPAR. These data indicate that uPA contributes to endogenous
      fibrinolysis in the pulmonary vasculature to the same extent as tPA in this model
      system. Binding of scuPA to its receptor promotes fibrinolytic activity in vivo
      as well as in vitro. The physical properties of fibrin clots, including size,
      age, and cellular composition, as well as heterogeneity in endothelial cell
      function, may modify the participation of uPA in endogenous fibrinolysis. (Blood.
      2000;96:1820-1826)

PMID- 10961883
TI  - LSP1 modulates leukocyte populations in resting and inflamed peritoneum.
AB  - Lymphocyte-specific protein 1, recently renamed leukocyte-specific protein 1
      (LSP1), is an F-actin binding protein expressed in lymphocytes, macrophages, and
      neutrophils in mice and humans. This study examines LSP1-deficient (Lsp1(-/-))
      mice for the development of myeloid and lymphocytic cell populations and their
      response to the development of peritonitis induced by thioglycollate (TG) and to
      a T-dependent antigen. Lsp1(-/-) mice exhibit significantly higher levels of
      resident macrophages in the peritoneum compared to wild-type (wt) mice, whereas
      the development of myeloid cells is normal. This increase, which is specific for
      conventional CD5(-) macrophages appears to be tissue specific and does not result
      from differences in adhesion to the peritoneal mesothelium. The level of
      peritoneal lymphocytes is decreased in Lsp1(-/-) mice without affecting a
      particular lymphocytic subset. The proportions of precursor and mature
      lymphocytes in the central and peripheral tissues of Lsp1(-/-) mice are similar
      to those of wt mice and Lsp1(-/-) mice mount a normal response to the T-dependent
      antigen, ovalbumin (OVA). On injection of TG, the Lsp1(-/-) mice exhibit an
      accelerated kinetics of changes in peritoneal macrophage and neutrophil numbers
      as compared to wt including increased influx of these cells. LSP1(-) neutrophils
      demonstrate an enhanced chemotactic response in vitro to N-formyl methionyl
      leucyl-phenylalanine (FMLP) and to the C-X-C chemokine, KC, indicating that their
      enhanced influx into the peritoneum may be a result of increased motility. Our
      data demonstrate that LSP1 is a negative regulator of neutrophil chemotaxis.
      (Blood. 2000;96:1827-1835)

PMID- 10961884
TI  - Activation of macrophage cytostatic effector mechanisms during acute graft-versus
      host disease: release of intracellular iron and nitric oxide-mediated cytostasis.
AB  - During acute graft-versus-host disease (GVHD) the activation of macrophages
      (Mphi) is mediated by 2 signals, interferon (IFN)-gamma and bacteria-derived
      lipopolysaccharide (LPS). A cascade of inflammatory responses that includes the
      release of mediators of tissue injury follows Mphi activation. Among the tissues
      characteristically targeted during acute GVHD are epithelial tissues of the skin
      and gastrointestinal tract that normally undergo continuous proliferation and are
      therefore sensitive to cytostatic processes. We have investigated whether Mphi
      can mediate cytostatic mechanisms capable of interrupting cell proliferation
      during acute GVHD. GVHD was induced in nonirradiated C57BL/6XAF(1) (B6AF(1)) mice
      by the injection of 60 x 10(6) (acute GVHD) or 30 x 10(6) (nonlethal GVHD)
      C57BL/6 (B6) lymphoid cells. Mphi from animals undergoing acute GVHD could be
      triggered by normally insignificant quantities of LPS to mediate a cytostatic
      effect on target cells, resulting in the complete shutdown of cellular
      proliferation. The same amounts of LPS had no effect on Mphi from normal or
      syngeneically transplanted animals. Mphi mediated the release of significant
      quantities of intracellular iron from target cells undergoing cytostasis.
      Reversal of cytostasis occurred following inhibition of nitric oxide (NO)
      production by N(G)-monomethyl-L-arginine (NMMA). Production of NO by LPS
      triggered Mphi reflected the severity of GVHD. NO release increased significantly
      during acute GVHD but was only transiently increased during nonlethal GVHD. The
      results provide evidence that, as a result of activation during acute GVHD, Mphi
      produce NO and induce the release of iron from target cells, resulting in a
      potent cytostatic effect that inhibits cellular proliferation. (Blood.
      2000;96:1836-1843)

PMID- 10961886
TI  - Kinetics of CXCR4 and CCR5 up-regulation and human immunodeficiency virus
      expansion after antigenic stimulation of primary CD4(+) T lymphocytes.
AB  - The chemokine receptors CCR5 and CXCR4 are coreceptors for the human
      immunodeficiency virus (HIV) and determine the cell tropism of different HIV
      strains. Previous studies on their regulation were performed under conditions of
      unspecific T-lymphocyte stimulation and provided conflicting results. To mimic
      physiologic conditions, highly purified primary Staphylococcus enterotoxin B
      (SEB)-reactive CD4 T lymphocytes were stimulated in the presence of autologous
      antigen-presenting cells and the kinetics of CCR5 and CXCR4 surface expression
      and HIV replication were studied. Both chemokine receptors were transiently up
      regulated with maximal expression at day 3 after stimulation. The stimulated T
      cells were equally susceptible to productive infection with R5-and X4-tropic
      virus strains. Thus, antigenic stimulation of T cells promotes efficient
      replication of both, T cell-tropic and macrophage-tropic HIV. (Blood.
      2000;96:1853-1856)

PMID- 10961885
TI  - Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine
      phosphorylation and transcriptional activity.
AB  - Interleukin-12 (IL-12) is a key immunoregulatory cytokine that promotes Th1
      differentiation and cell-mediated immune responses. The transcription factor
      STAT4 (signal transducer and activator of transcription 4) is an important
      element in mediating IL-12 signals, as evidenced by the fact that STAT4(-/-) mice
      display impaired responsiveness to IL-12 and deficient Th1 differentiation. STAT4
      is inducibly phosphorylated on tyrosine and serine in response to IL-12, but the
      kinase(s) responsible for the latter event is unknown. Here we show that IL-12
      induces STAT4 phosphorylation on serine 721 and that mutation of serine 721
      interferes with STAT4 transcriptional activity. In addition, we show that
      mutation of tyrosine 693 abrogates IL-12-induced STAT4 tyrosine phosphorylation
      and transcriptional activity. Although the site surrounding serine 721 is an
      optimum consensus sequence for mitogen-activated family of protein kinases
      (MAPKs)-mediated phosphorylation, we demonstrate that IL-12 does not induce
      extracellular signal-regulated kinase (ERK) or c-Jun N-terminal kinase (JNK)
      activation in T and natural killer (NK) cells and that IL-12-induced STAT4
      transcriptional activity is not affected by these kinases. Rather, we show that
      IL-12 induces p38 activation. Moreover, we demonstrate that p38alpha and its
      upstream activator, MKK6, phosphorylate STAT4 on serine 721, and are required for
      STAT4 full transcriptional activity induced by IL-12, establishing the
      MKK6/p38alpha/STAT4 pathway as an important mediator of IL-12 actions. (Blood.
      2000;96:1844-1852)

PMID- 10961887
TI  - Mature dendritic cells pulsed with freeze-thaw cell lysates define an effective
      in vitro vaccine designed to elicit EBV-specific CD4(+) and CD8(+) T lymphocyte
      responses.
AB  - Immunotherapy trials targeting the induction of tumor-reactive T-cell responses
      in cancer patients appear to hold significant promise. Because nonmutated lineage
      specific antigens and mutated idiotypic antigens may be coexpressed by tumor
      cells, the use of autologous tumor material to promote the broadest range of
      antitumor T-cell specificities has significant clinical potential in cancer
      vaccination trials. As a model for vaccination in the cancer setting, we chose to
      analyze the promotion of T-cell responses against Epstein-Barr virus (EBV)
      transformed B-lymphoblastoid cell line (B-LCL)-derived antigens in vitro. A
      series of bulk antigenic formats (freeze-thaw lysate, trifluoroacetic acid
      lysate, extracted membranes, affinity-purified MHC class I- and class II
      presented peptides, acid-eluted peptides) prepared from EBV B-LCLs were tested
      for their ability to stimulate EBV B-LCL-reactive CD4(+) and CD8(+) T lymphocytes
      in vitro when pulsed onto autologous dendritic cells (DCs). DC presentation of
      freeze-thaw lysate material derived from (either autologous or allogeneic) EBV B
      LCLs with an Mr of 10 kd or larger stimulated optimal anti-EBV B-LCL
      responsiveness from freshly isolated CD4(+) and CD8(+) peripheral blood T cells.
      These in vivo "memory" T-cell responses were observed only in EBV-seropositive
      donors. CD4(+) T-cell responses to lysate-pulsed DCs were Th1 type (ie, strong
      interferon-gamma and weak interleukin-5 responses). While CD8(+) T-cell responses
      were also observed in interferon-gamma Elispot assays and in cytotoxicity assays,
      these responses were of low frequency unless the DC stimulators were induced to
      "mature" after being fed with tumor lysates. Optimal-length, naturally processed,
      and MHC class I- or class II-presented tumor peptides were comparatively poorly
      immunogenic in this model system. (Blood. 2000;96:1857-1864)

PMID- 10961888
TI  - Differentiation of myeloid dendritic cells into CD8alpha-positive dendritic cells
      in vivo.
AB  - Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting
      cells (APC) with varying phenotypes. For example, in mice, CD8alpha(+) and
      CD8alpha(-) DC are thought to represent cells of lymphoid and myeloid origin,
      respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they
      do not express CD8alpha, but they do express high levels of myeloid antigens such
      as CD11b and FcgammaR. By contrast, thymic DC, which derive from a lymphoid
      related progenitor, express CD8alpha but only low levels of myeloid antigens.
      CD8alpha(+) DC are also found in the spleen and lymph nodes (LN), but the origin
      of these cells has not been determined. By activating and labeling CD8alpha(-)
      epidermal LC in vivo, it was found that these cells expressed CD8alpha on
      migration to the draining LN. Similarly, CD8alpha(-) LC generated in vitro from a
      CD8 wild-type mouse and injected into the skin of a CD8alphaKO mouse expressed
      CD8alpha when they reached the draining LN. The results also show that
      CD8alpha(+) LC are potent APC. After migration from skin, they localized in the T
      cell areas of LN, secreted high levels of interleukin-12, interferon-gamma, and
      chemokine-attracting T cells, and they induced antigen-specific T-cell
      activation. These results demonstrate that myeloid DC in the periphery can
      express CD8alpha when they migrate to the draining LN. CD8alpha expression on
      these DC appears to reflect a state of activation, mobilization, or both, rather
      than lineage. (Blood. 2000;96:1865-1872)

PMID- 10961889
TI  - Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell
      production of soluble osteoclastogenic cytokines.
AB  - In unstimulated conditions osteoclast renewal occurs as a result of the stromal
      cell production of the key osteoclastogenic factors, receptor activator of NFkB
      ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Inflammation is
      known to cause increased osteoclastogenesis; however, the mechanisms responsible
      for this phenomenon are poorly understood. We now show that interleukin-1 (IL-1)
      and tumor necrosis factor alpha (TNFalpha), cytokines typically produced in
      inflammatory conditions, increase the stromal cell production of IL-7. This
      factor, in turn, up-regulates production of osteoclastogenic cytokines by T cells
      leading to stimulation of osteoclast (OC) formation. Although T cells were found
      to produce soluble forms of both RANKL and M-CSF, saturating concentrations of
      osteoprotegerin failed to inhibit approximately 40% of the OC formation,
      suggesting that IL-7 acts via both RANKL-dependent and RANKL-independent
      pathways. Despite the identification of T-cell-secreted M-CSF, this cytokine was
      not essential for either RANKL-dependent or -independent OC formation, suggesting
      that T cells secrete other cytokines capable of substituting for M-CSF action. On
      the basis of our data, we propose a novel mechanism for inflammatory bone loss in
      which induction of IL-7 from stromal cells by IL-1 and TNFalpha leads to the
      production of soluble osteoclastogenic cytokines by T cells. Thus, the mechanism
      by which IL-7 causes bone resorption involves the activation of T cells and the T
      cell-dependent augmentation of osteoclastogenesis. (Blood. 2000;96:1873-1878)

PMID- 10961890
TI  - Heparin and heparan sulfate bind interleukin-10 and modulate its activity.
AB  - Glycosaminoglycans (GAG) are a group of negatively charged molecules that have
      been shown to bind and directly regulate the bioactivity of growth factors and
      cytokines such as basic fibroblast growth factor, transforming growth factor
      beta, IL-7, and interferon-gamma. The ability of GAG to interact with human IL-10
      (hIL-10) and the effect of these interactions on its biologic activity were
      analyzed. It was demonstrated by affinity chromatography that hIL-10 binds
      strongly to heparin-agarose at physiological pH. Biosensor-based binding kinetic
      analysis indicated an equilibrium dissociation constant, K(d), of 54 nmol/L for
      this interaction. Human IL-10 stimulated CD16 and CD64 expression on the
      monocyte/macrophage population within peripheral blood mononuclear cells, with
      optimal concentrations between 1 and 10 ng/mL. Soluble heparin, heparan sulfate,
      chondroitin sulfate, and dermatan sulfate were shown to inhibit the hIL-10
      induced expression of CD16 and CD64 in a concentration-dependent manner. Heparin
      and heparan sulfate were most effective with IC(50) values of 100 to 500
      microg/mL. Considerably higher concentrations of dermatan sulfate and chondroitin
      4-sulfate were required with an IC(50) of 2,000 to 5,000 microg/mL, whereas
      chondroitin 6-sulfate was essentially inactive. The antagonistic effect of
      heparin on hIL-10 activity was shown to be dependent on N-sulfation, inasmuch as
      de-N-sulfated heparin had little or no inhibitory effect on the IL-10- induced
      expression of CD16, whereas the effect of de-O-sulfated heparin was comparable to
      that of unmodified heparin. Furthermore, the inhibition of cell-bound
      proteoglycan sulfation reduced the hIL-10-mediated expression of CD16 molecules
      on monocytes/macrophages. Taken together, these findings support the hypothesis
      that soluble and cell-surface GAG and, in particular, their sulfate groups are
      important in binding and modulation of hIL-10 activity. (Blood. 2000;96:1879
      1888)

PMID- 10961891
TI  - European Task Force on Lymphoma project on lymphocyte predominance Hodgkin
      disease: histologic and immunohistologic analysis of submitted cases reveals 2
      types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes.
AB  - Paraffin blocks and clinical data from 521 patients with lymphocyte predominance
      Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16
      European and United States oncological centers to establish the pathologic and
      clinical characteristics of a large patient cohort, to determine how frequent T
      cell-rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential
      diagnostic criteria distinguishing between the 2 lymphoma categories. For this
      purpose, conventionally and immunohistologically stained sections were reviewed
      by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219
      of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to
      the presence of a new variant of classical Hodgkin disease (CHD), which
      resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and,
      in terms of the immunophenotype of the tumor cells, CHD and was designated
      nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted-as in
      nodular LPHD-predominantly of B cells but differed from those present in LPHD in
      that they represented expanded mantle zones with atrophic germinal centers.
      Clinically, patients with LPHD and NLRCHD showed similar disease characteristics
      at presentation but differed in the frequency of multiple relapses and prognosis
      after relapse. Patients with LPHD and NLRCHD clearly differed from patients with
      CHD with nodular sclerosis or mixed cellularity, as they presented with an
      earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD
      cases showed a complete or partial nodular growth pattern, their differentiation
      from TCRLBCL was a rare problem in the present series. (Blood. 2000;96:1889-1899)

PMID- 10961892
TI  - Effective targeting of tumor vasculature by the angiogenesis inhibitors
      vasostatin and interleukin-12.
AB  - Solid tumors are dependent on preexisting vasculature and neovascularization for
      their growth. Successful cancer therapies targeting the tumor vasculature would
      be expected to block the existing tumor blood supply and to prevent tumor
      neovascularization. We tested the antitumor activity of experimental therapy with
      2 distinct antiangiogenic drugs. Vasostatin inhibits endothelial cell growth and
      neovascularization, and interleukin-12 (IL-12) targets the tumor vasculature
      acting through interferon-gamma (IFN-gamma) and the downstream chemokines
      interferon-inducible protein-10 (IP-10) and monokine induced by IFN-gamma.
      Individually, vasostatin and IL-12 produced distinct efficacy profiles in trials
      aimed at reducing tumor growth in athymic mice. In combination, these inhibitors
      halted the growth of human Burkitt lymphoma, colon carcinoma, and ovarian
      carcinoma. Thus, cancer therapy that combines distinct inhibitors of angiogenesis
      is a novel, effective strategy for the experimental treatment of cancer. (Blood.
      2000;96:1900-1905)

PMID- 10961893
TI  - A carboxy-terminal deletion mutant of Notch1 accelerates lymphoid oncogenesis in
      E2A-PBX1 transgenic mice.
AB  - PBX1 is a proto-oncogene that plays important roles in pattern formation during
      development. It was discovered as a fusion with the E2A gene after chromosomal
      translocations in a subset of acute leukemias. The resulting E2a-Pbx1 chimeric
      proteins display potent oncogenic properties that appear to require dimerization
      with Hox DNA binding partners. To define molecular pathways that may be impacted
      by E2a-Pbx1, a genetic screen consisting of neonatal retroviral infection was
      used to identify genes that accelerate development of T-cell tumors in E2A-PBX1
      transgenic mice. Retroviral insertions in the Notch1 gene were observed in 88% of
      tumors arising with a shortened latency. Among these, approximately half created
      a Notch(IC) allele, encoding the intracellular, signaling portion of Notch1,
      suggesting a synergistic interaction between the Notch and E2a-Pbx1 pathways in
      oncogenesis. The remaining proviral insertions involving Notch1 occurred in a
      more 3' exon, resulting in truncating mutations that deleted the carboxy-terminal
      region of Notch1 containing negative regulatory sequences (Notch1(DeltaC)). In
      contrast to Notch(IC), forced expression of Notch1(DeltaC) in transgenic mice did
      not perturb thymocyte growth or differentiation. However, mice transgenic for
      both the E2A-PBX1 and Notch1(DeltaC) genes displayed a substantially shortened
      latency for tumor development compared with E2A-PBX1 single transgenic mice.
      These studies reveal a novel mechanism for oncogenic activation of Notch1 and
      demonstrate a collaborative relationship between 2 cellular oncogenes that also
      contribute to cell fate determination during embryonic development. (Blood.
      2000;96:1906-1913)

PMID- 10961894
TI  - Acute myeloblastic leukemic cells acquire cellular cytotoxicity under genotoxic
      stress: implication of granzyme B and perforin.
AB  - Granzyme B (GrB) and perforin (PFN) are the major components of cytoplasmic
      granules contained in immune cellular effectors. The granule secretory pathway is
      one of the mechanisms by which these cells exert their cellular cytotoxicity.
      Recently, it has been reported that GrB and PFN are also present in circulating
      hemopoietic CD34(+) progenitor cells mobilized by chemotherapy and granulocyte
      colony stimulating factor, whereas these proteins are undetected in steady-state
      peripheral CD34(+) cells. In this study, we hypothesized that anticancer agents
      may increase GrB and PFN expression in immature myeloid leukemic cells and that
      these treated leukemic cells become cellular effectors through a granule
      dependent mechanism. Our results show that KG1a, HEL, and TF-1 CD34(+) acute
      myeloblastic leukemia cells expressed both GrB and PFN. Moreover, ionizing
      radiation, aracytine, and etoposide not only increase GrB and PFN expression but
      also conferred potent cellular cytotoxicity to these cells toward various
      cellular targets. Cellular cytotoxicity required cell-cell contact, was not
      influenced by anti-tumor necrosis factor alpha or anti-Fas blocking antibodies,
      and was abrogated by GrB inhibitors or antisense. These results suggest that,
      when exposed to genotoxic agents, immature leukemic cells acquire potent GrB- and
      PFN-dependent cellular cytotoxicity that can be potentially directed against
      normal residual myeloid progenitors or immune effectors. (Blood. 2000;96:1914
      1920)

PMID- 10961895
TI  - Prognostic significance of survivin expression in diffuse large B-cell lymphomas.
AB  - Survivin is an inhibitor of apoptosis overexpressed in various human cancers but
      undetectable in normal differentiated tissues. A potential expression and
      prognostic significance of survivin was studied in 222 patients with diffuse
      large B-cell lymphomas (centroblastic, 96%; immunoblastic, 4%). All patients were
      enrolled between 1987 and 1993 (median follow-up, 7 years) in the LNH87 protocol
      of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) and treated either with
      the reference ACVBP arm (doxorubicin, cyclophosphamide, vindesine, bleomycin, and
      prednisone)[AU3A] (n = 79) or other experimental anthracycline-containing
      regimens (n = 143). The characteristics of these patients were median age of 56
      years; serum lactate dehydrogenase (LDH) greater than 1N, 60%; stage III-IV, 55%;
      performance status, according to the Eastern Cooperative Oncology Group (ECOG)
      scale, more than 1, 23%; extranodal sites more than 1, 29%; mass more than 10 cm,
      44%; bone marrow involvement, 15%. Of the 222 patients studied, 134 (60%)
      revealed survivin expression in virtually all tumor cells by
      immunohistochemistry. The overall 5-year survival rate was significantly lower in
      patients with survivin expression than in those without (40% vs 54%, P =.02).
      Multivariate analysis incorporating prognostic factors from the International
      Prognostic Index (IPI) identified survivin expression as an independent
      predictive parameter on survival (P =.03, relative risk [RR] = 1.6) in addition
      to LDH (P =.02, RR = 1.6), stage (P =.03, RR = 1.7), and ECOG scale (P =.05, RR =
      1.6). A second analysis incorporating IPI as a unique parameter demonstrated that
      survivin expression (P =.02, RR = 1.6) remained a prognostic factor for survival
      independently of IPI (P =.001, RR = 1.5). Survivin expression may be considered a
      new unfavorable prognostic factor of diffuse large B-cell lymphoma. (Blood.
      2000;96:1921-1925)

PMID- 10961896
TI  - Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy.
AB  - Approximately 20% of B-lineage acute lymphoblastic leukemias are not cured by
      traditional chemotherapy. The possibility was examined that residual leukemic
      cells that potentially contribute to relapse are harbored in association with
      fibroblastic stromal cells in the bone marrow. Modulation of cytarabine (Ara-C)
      and etoposide (VP-16) efficacy by bone marrow stromal cells in vitro was
      investigated. Stromal cell coculture was shown to sustain the proliferation of B
      lineage leukemic cells and to reduce leukemic cell apoptosis when exposed to Ara
      C or VP-16. Direct contact with stromal cells was essential for the protection of
      leukemic cells during chemotherapy, whereas soluble factors had negligible
      effect. Specifically, signaling mediated through interaction with the stromal
      cell adhesion molecule VCAM-1 was required to maintain the maximum viability of
      leukemic cells during Ara-C and VP-16 exposure. In contrast, the interaction of
      leukemic cells with fibronectin did not confer significant resistance to either
      chemotherapeutic agent. These observations suggest a role for the bone marrow
      microenvironment in modulating the response of B-lineage leukemic cells to Ara-C
      or VP-16, and they indicate specific molecular interactions that may be important
      in determining the sensitivity of leukemic cells to treatment. (Blood.
      2000;96:1926-1932)

PMID- 10961898
TI  - Abnormal rearrangement within the alpha/delta T-cell receptor locus in lymphomas
      from Atm-deficient mice.
AB  - Atm-deficient mice (Atm(-/-)) recapitulate many aspects of the ataxia
      telangiectasia (AT) syndrome, including the susceptibility to tumors of lymphoid
      origin. To investigate the mechanism of tumorigenesis, we have examined a panel
      of 8 thymic lymphomas from Atm(-/-) mice. All Atm(-/-) tumors are of thymic
      lymphoblastoid origin, display an immature CD3(-) and CD4(+)/CD8(+) phenotype,
      and arise coincident with V(D)J recombination. Cytogenetically, all tumors are
      diploid or near diploid but exhibit multiple chromosome aberrations with an
      average of 4 abnormal chromosomes per tumor. All the tumors revealed chromosome
      14 rearrangements precisely at the T-cell receptoralpha/delta (Tcralpha/delta)
      locus, suggesting the involvement of V(D)J recombination in these translocations.
      In addition, 11.5% of Atm(-/-) peripheral T cells showed chromosome 14
      translocations, suggesting that rearrangements at the Tcralpha/delta locus occur
      early during tumor development in the absence of ATM. However, additional genetic
      aberrations are required for tumorigenesis. For example, translocations involving
      chromosome 12, often with chromosome 14 (more than 60%), and partial or complete
      trisomy of chromosome 15, with copy number increases of the c-myc oncogene were
      frequently observed. These observations suggest that ATM is required for normal
      rearrangement of the Tcralpha/delta locus but not for V(D)J recombination at
      other loci. The mechanisms that lead to tumorigenesis may be due to the
      involvement of ATM in monitoring double-stranded DNA breaks. (Blood. 2000;96:1940
      1946)

PMID- 10961897
TI  - Bcr-Abl kinase down-regulates cyclin-dependent kinase inhibitor p27 in human and
      murine cell lines.
AB  - Chronic myeloid leukemia (CML) is a malignant stem cell disease characterized by
      an expansion of myeloid progenitor cells expressing the constitutively activated
      Bcr-Abl kinase. This oncogenic event causes a deregulation of apoptosis and cell
      cycle progression. Although the molecular mechanisms protecting from apoptosis in
      CML cells are well characterized, the cell cycle regulatory event is poorly
      understood. An inhibitor of the cyclin-dependent kinases, p27, plays a central
      role in the regulation of growth factor dependent proliferation of hematopoietic
      cells. Therefore, we have analyzed the influence of Bcr-Abl in the regulation of
      p27 expression in various hematopoietic cell systems. An active Bcr-Abl kinase
      causes down-regulation of p27 expression in murine Ba/F3 cells and human M07
      cells. Bcr-Abl blocks up-regulation of p27 after growth factor withdrawal and
      serum reduction. In addition, p27 induction by transforming growth factor-beta
      (TGF-beta) is completely blocked in Bcr-Abl positive M07/p210 cells. This
      deregulation is directly mediated by the activity of the Bcr-Abl kinase. A Bcr
      Abl kinase inhibitor completely abolishes p27 down-regulation by Bcr-Abl in both
      Ba/F3 cells transfected either with a constitutively active Bcr-Abl or with a
      temperature sensitive mutant. The down-regulation of p27 by Bcr-Abl depends on
      proteasomal degradation and can be blocked by lactacystin. Overexpression of wild
      type p27 partially antagonizes Bcr-Abl-induced proliferation in Ba/F3 cells. We
      conclude that Bcr-Abl promotes cell cycle progression and activation of cyclin
      dependent kinases by interfering with the regulation of the cell cycle inhibitory
      protein p27. (Blood. 2000;96:1933-1939)

PMID- 10961899
TI  - V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in
      follicular lymphoma.
AB  - Using DNA fiber fluorescence in-situ hybridization (FISH) and 3-color interphase
      FISH, 2 cases of follicular lymphoma were identified in which the BCL2 gene was
      excised from 18q21 and inserted into the immunoglobulin heavy chain (IGH) locus
      at 14q32. Both the insertion breakpoint at 14q32 and the deletion breakpoint at
      18q21 were cloned using inverse polymerase chain reaction. Sequence analysis
      showed that the JH sequences were juxtaposed to the 5'-side of BCL2, and the DH
      sequences were juxtaposed to the 3'-side of BCL2. There were breakpoints at both
      the JH and DH recombination signal sequences, and N-nucleotides were present at
      all breakpoint junctions. At the BCL2 locus, the 3'-breakpoints in both cases
      were localized at exactly the same nucleotide position, 6. 2 kilobase downstream
      of the major breakpoint region, directly adjacent to a complete cryptic
      recombination signal sequence (RSS) consisting of a heptamer, a nonamer, and a 23
      base pair (bp) spacer. The BCL2 5'-breakpoints were approximately 600 bp upstream
      of the gene, within the CA repeats. Although less evident than for the BCL2 3'
      breakpoints, cryptic RSSs were also identified at these breakpoints, with a 12-bp
      spacer. On the basis of structural characteristics of these rearrangements, a
      model is proposed in which the BCL2 gene is deleted from its locus by
      recombination activation gene-1/-2 (RAG-1/-2)-mediated excision. The gene is
      subsequently inserted into the recombining IGH locus, a process involving the
      formation of hybrid joints between the IGH coding ends and the BCL2 signal ends.
      (Blood. 2000;96:1947-1952)

PMID- 10961900
TI  - Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and
      alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity.
AB  - Myeloma is a unique hematologic malignancy that exclusively homes in the bone
      marrow and induces massive osteoclastic bone destruction presumably by producing
      cytokines that promote the differentiation of the hematopoietic progenitors to
      osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow
      stromal cells influence the expression of the malignant phenotype in myeloma
      cells. This study examined the role of the interactions between myeloma cells and
      neighboring stromal cells in the production of osteoclastogenic factors to
      elucidate the mechanism underlying extensive osteoclastic bone destruction. A
      murine myeloma cell line 5TGM1, which causes severe osteolysis, expresses
      alpha(4)beta(1)-integrin and tightly adheres to the mouse marrow stromal cell
      line ST2, which expresses the vascular cell adhesion molecule-1 (VCAM-1), a
      ligand for alpha(4)beta(1)-integrin. Co-cultures of 5TGM1 with primary bone
      marrow cells generated tartrate-resistant acid phosphatase-positive
      multinucleated bone-resorbing osteoclasts. Co-cultures of 5TGM1 with ST2 showed
      increased production of bone-resorbing activity and neutralizing antibodies
      against VCAM-1 or alpha(4)beta(1)-integrin inhibited this. The 5TGM1 cells
      contacting recombinant VCAM-1 produced increased osteoclastogenic and bone
      resorbing activity. The activity was not blocked by the neutralizing antibody to
      known osteoclastogenic cytokines including interleukin (IL)-1, IL-6, tumor
      necrosis factor, or parathyroid hormone-related peptide. These data suggest that
      myeloma cells are responsible for producing osteoclastogenic activity and that
      establishment of direct contact with marrow stromal cells via alpha(4)beta(1)
      integrin/VCAM-1 increases the production of this activity by myeloma cells. They
      also suggest that the presence of stromal cells may provide a microenvironment
      that allows exclusive colonization of myeloma cells in the bone marrow. (Blood.
      2000;96:1953-1960)

PMID- 10961901
TI  - Natural killer cell dysfunction and apoptosis induced by chronic myelogenous
      leukemia cells: role of reactive oxygen species and regulation by histamine.
AB  - Natural killer (NK) cells are deficient in patients with chronic myelogenous
      leukemia (CML), but the mechanisms responsible for the dysfunction are not
      completely understood. This study reports that CML cells effectively inhibit the
      baseline and interleukin-2 (IL-2)-induced NK cell cytotoxicity against a CML cell
      derived line (K562). A sizable fraction of NK cells subsequently acquired
      features characteristic of programmed cell death/apoptosis. The CML cell-mediated
      inhibition of NK cells required triggering of reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase-mediated formation of reactive oxygen
      species (ROS) and was prevented by catalase, a scavenger of ROS, and by
      histamine, acting via H(2)-receptor-mediated inhibition of ROS production in CML
      cells. In contrast, nonmalignant neutrophilic granulocytes inhibited NK cells via
      ROS production without the requirement of exogenous NADPH oxidase-triggering
      stimuli. We propose that paracrine production of ROS may contribute to the
      dysfunction of NK cells in CML and that histamine may serve as an autocrine
      inhibitor of ROS formation in leukemic granulocytes. (Blood. 2000;96:1961-1968)

PMID- 10961902
TI  - Pathologic gene expression in Gaucher disease: up-regulation of cysteine
      proteinases including osteoclastic cathepsin K.
AB  - Deficiency of lysosomal acid beta-glucosidase induces glycolipid storage in the
      macrophages of Gaucher disease but the pathways of multisystem tissue injury and
      destruction are unknown. To investigate the cognate molecular pathology of this
      inflammatory disorder, genes that were differentially expressed in spleen samples
      from a patient with Gaucher disease (Gaucher spleen) were isolated. Of 64
      complementary DNA (cDNA) fragments sequenced from an enriched Gaucher cDNA
      library, 5 encode lysosomal proteins (cathepsins B, K, and S, alpha-fucosidase,
      and acid lipase), 10 encode other known proteins, and 2 represent novel sequences
      from human macrophage cell lines. Transcript abundance of the cathepsins, novel
      genes, pulmonary and activation-regulated chemokine (PARC), and NMB, a putative
      tumor suppressor gene, was greatly increased. Immunoblotting showed increased
      mature forms of all 3 cathepsins found in samples of Gaucher spleens.
      Immunofluorescence microscopy showed strong cathepsin B and K reactions in
      sinusoidal endothelium and Gaucher cells. The respective means, plus or minus SD,
      of cathepsin B, K, and S activities were 183 +/- 35, 97 +/- 39, and 91 +/- 45
      nmol/min/mg protein in 4 Gaucher spleens, and 26 +/- 4, 10.5 +/- 2, and 4.0 +/-
      2.1 nmol/min/mg protein in 3 control spleens. Plasma cathepsin B, K, and S
      activities were also elevated in Gaucher disease plasma (P <.001), but compared
      with control plasma samples, neither cathepsin B nor K activities were
      significantly elevated in 8 patients with nonglycosphingolipid lysosomal storage
      diseases or in 9 patients with other glycosphingolipidoses, which suggests
      disease specificity. All 3 cathepsin activities were increased 2-fold to 3-fold
      in Gaucher sera compared with control sera. In all 6 patients treated by enzyme
      replacement for 16-22 months, serum cathepsin activities decreased significantly
      (P <.01). Longitudinal studies confirmed the progressive reduction of proteinase
      activities during imiglucerase therapy but in 3 Gaucher patients with mild
      disease not so treated, serum cathepsin activities remained constant or increased
      during follow-up. Enhanced expression of cysteine proteinases may promote tissue
      destruction. Moreover, the first identification of aberrant cathepsin K
      expression in hematopoietic tissue other than osteoclasts implicates this
      protease in the breakdown of the matrix that characterizes lytic bone lesions in
      Gaucher disease. (Blood. 2000;96:1969-1978)

PMID- 10961903
TI  - Interleukin-15 enhances neutrophil functional activity in patients with human
      immunodeficiency virus infection.
AB  - Polymorphonuclear leukocyte (PMN) dysfunction has been reported in human
      immunodeficiency virus (HIV)-infected patients. Interleukin (IL)-15 is a recently
      discovered cytokine that potentiates antimicrobial functions of normal PMNs. We
      evaluated the in vitro effect of IL-15 on chemotaxis and fungicidal activity of
      PMNs from 9 patients with untreated advanced HIV infection, 8 patients with viral
      suppression after 52 to 130 weeks of highly active antiretroviral therapy
      (HAART), and 12 patients with treatment failure. We also studied oxidative burst
      and apoptosis of PMNs in 5 patients with untreated advanced HIV infection. Twelve
      healthy donors were included as controls. Chemotaxis and fungicidal activity of
      unprimed PMNs was significantly lower in patients with untreated HIV infection
      compared with controls. After incubation with IL-15, a significant increase in
      PMN chemotaxis and fungicidal activity was found; moreover, IL-15 induced a
      significant reduction in the number of apoptotic HIV(+) PMNs. IL-15 did not
      modulate oxidative burst of HIV(+) PMNs as measured by chemiluminescence
      production. The in vitro priming of PMNs with IL-15 determined a complete
      reversal of defective chemotaxis and killing in all HAART-treated patients with
      long-term HIV suppression. IL-15 significantly enhanced chemotaxis and fungicidal
      activity also in patients with HAART failure. In conclusion, IL-15 is an
      important cytokine in the activation of the functional properties of HIV(+) PMNs,
      by delaying apoptosis and enhancing chemotaxis and fungicidal activity. The
      potent stimulant effect of IL-15 on PMN function was observed in antiretroviral
      naive patients as well as in individuals who were receiving HAART, including
      those with treatment failure. (Blood. 2000;96:1979-1984)

PMID- 10961904
TI  - Red cells from glutathione peroxidase-1-deficient mice have nearly normal
      defenses against exogenous peroxides.
AB  - The role of glutathione peroxidase in red cell anti-oxidant defense was examined
      using erythrocytes from mice with a genetically engineered disruption of the
      glutathione peroxidase-1 (GSHPx-1) gene. Because GSHPx-1 is the sole glutathione
      peroxidase in the erythrocyte, all red cell GSH peroxidase activity was
      eliminated. Oxidation of hemoglobin and membrane lipids, using the cis-parinaric
      acid assay, was determined during oxidant challenge from cumene hydroperoxide and
      H(2)O(2). No difference was detected between wild-type red cells and GSHPx-1
      deficient cells, even at high H(2)O(2) exposures. Thus, GSHPx-1 appears to play
      little or no role in the defense of the erythrocyte against exposure to peroxide.
      Simultaneous exposure to an H(2)O(2) flux and the catalase inhibitor 3-amino
      1,2,4-triazole supported this conclusion. Hemoglobin oxidation occurred only when
      catalase was depleted. Circulating erythrocytes from the GSHPx-1-deficient mice
      exhibited a slight reduction in membrane thiols, indicating that high exposure to
      peroxides might occur naturally in the circulation. (Blood. 2000;96:1985-1988)

PMID- 10961905
TI  - CD34 expression by murine hematopoietic stem cells mobilized by granulocyte
      colony-stimulating factor.
AB  - Controversy has existed about CD34 expression by hematopoietic stem cells. We
      recently reported that CD34 expression reflects the activation state of stem
      cells by using a murine transplantation model. It has been generally held that
      mobilized blood stem cells express CD34.However, it has also been reported that
      mobilized stem cells and progenitors are in G0/G1 phases of the cell cycle. To
      address the state of CD34 expression by the mobilized stem cells, we again used
      the mouse transplantation model. We prepared CD34(-) and CD34(+) populations of
      nucleated blood cells from granulocyte colony-stimulating factor-treated Ly-5.1
      mice and assayed each population for long-term engrafting cells in lethally
      irradiated Ly-5.2 mice. The majority of the stem cells were in the CD34(+)
      population. The CD34 expression by mobilized stem cells was reversible because re
      transplantation of Ly-5.1 CD34(-) marrow cells harvested from the Ly-5.2
      recipients of CD34(+)-mobilized stem cells 8 months posttransplantation revealed
      long-term engraftment. These results may support the use of total CD34(+) cells
      in mobilized blood as a predictor for engraftment and CD34 selection for
      enrichment of human stem cells. (Blood. 2000;96:1989-1993)

PMID- 10961906
TI  - Class I-unrestricted noncytotoxic anti-HTLV-I activity of CD8(+) T cells.
AB  - Although it is widely believed that viral clearance is mediated principally by
      the destruction of infected cells by cytotoxic T cells, noncytolytic antiviral
      activity of CD8(+) T cells may play a role in preventing the progression to
      disease in infections with immunodeficiency viruses and hepatitis B virus. We
      demonstrate here that (1) replication of human T-lymphotropic virus type I (HTLV
      I) is more readily detected from CD8(+) T-cell-depleted (CD8(-)) peripheral blood
      mononuclear cells (PBMCs) of healthy HTLV-I carriers than from unfractionated
      PBMCs, (2) cocultures of CD8(-) PBMCs with autologous or allogeneic CD8(+) T
      cells suppressed HTLV-I replication, and (3) CD8(+) T-cell anti-HTLV-I activity
      is not abrogated in trans-well cultures in which CD8(+) cells are separated from
      CD8(-) PBMCs by a permeable membrane filter. These results suggest that class I
      unrestricted noncytolytic anti-HTLV-I activity is mediated, at least in part by a
      soluble factor(s), and may play a role in the pathogenesis of HTLV-I infection.
      (Blood. 2000;96:1994-1995)

PMID- 10961907
TI  - A gene-anchored map position of the rat warfarin-resistance locus, Rw, and its
      orthologs in mice and humans.
AB  - The locus underlying hereditary resistance to the anticoagulant warfarin (symbol
      in the rat, Rw) was placed in relation to 8 positionally mapped gene-anchored
      microsatellite loci whose positions were known in the genome maps of the rat,
      mouse, and human. Rw segregated with the markers Myl2 (zero recombinants) and
      Itgam, Il4r, and Fgf2r (one recombinant each) during linkage analysis in a
      congenic warfarin- and bromadiolone-resistant laboratory strain of rats.
      Comparative ortholog mapping between rat, mouse, and human placed Rw onto mouse
      chromosome 7 at about 60 to 63 cM and onto one of the human chromosomes 10q25.3
      26, 12q23-q24.3, and 16p13.1-p11. (Blood. 2000;96:1996-1998)

PMID- 10961908
TI  - Chimeric Fv-zeta or Fv-epsilon receptors are not sufficient to induce activation
      or cytokine production in peripheral T cells.
AB  - In current clinical trials, chimeric antibody-like receptors fused to signaling
      domains derived from TCR-zeta or Fc(epsilon)RIgamma-chain are tested for their
      ability to lyse tumor cells in vivo. In this study, the function of primary T
      cells expressing such receptors has been investigated in transgenic mice. These
      receptors cannot induce proliferation of resting T cells or trigger the
      production of optimal amounts of cytokines. It is further demonstrated that an
      initial low presence of cytokine message and protein is disappearing rather fast,
      whereas the triggering of endogenous TCR/CD3 in the same cells leads to normal
      prolonged cytokine production. The direct clinical relevance of these findings is
      further underlined by the increased in vivo tumor rejection by T cells expressing
      chimeric receptors in presence of exogenous interleukin-2. Therefore, adoptive T
      cell therapy using primary T cells transfected with single chain receptors might
      benefit substantially from the accompanying administration of cytokines. (Blood.
      2000;96:1999-2001)

PMID- 10961909
TI  - A unified Haseman-Elston method for testing linkage with quantitative traits.
AB  - The Haseman and Elston (H-E) method uses a simple linear regression to model the
      squared trait difference of sib pairs with the shared allele identical by descent
      (IBD) at marker locus for linkage testing. Under this setting, the squared mean
      corrected trait sum is also linearly related to the IBD sharing. However, the
      resulting slope estimate for either model is not efficient. In this report, we
      propose a simple linkage test that optimally uses information from the estimates
      of both models. We also demonstrate that the new test is more powerful than both
      the traditional one and the recently revisited H-E methods.

PMID- 10961910
TI  - Consistent long-range linkage disequilibrium generated by admixture in a Bantu
      Semitic hybrid population.
AB  - Both the optimal marker density for genome scans in case-control association
      studies and the appropriate study design for the testing of candidate genes
      depend on the genomic pattern of linkage disequilibrium (LD). In this study, we
      provide the first conclusive demonstration that the diverse demographic histories
      of human populations have produced dramatic differences in genomewide patterns of
      LD. Using a panel of 66 markers spanning the X chromosome, we show that, in the
      Lemba, a Bantu-Semitic hybrid population, markers </= approximately 21 cM apart
      have a significantly greater tendency to show LD than do unlinked markers. In
      three populations with less evidence of admixture, however, excess LD disappears
      >2 cM. Moreover, analysis of Bantu and Ashkenazi populations as putative parental
      populations of the Lemba shows a significant relationship between allele
      frequency differentials and the LD observed in the Lemba, which demonstrates that
      much of the excess LD is due to admixture. Our results suggest that demographic
      history has such a profound effect on LD that it will not be possible to predict
      patterns a priori but that it will be necessary to empirically evaluate the
      patterns in all populations of interest.

PMID- 10961912
TI  - The chemical and biological versatility of riboflavin.
AB  - Since their discovery and chemical characterization in the 1930s, flavins have
      been recognized as being capable of both one- and two-electron transfer
      processes, and as playing a pivotal role in coupling the two-electron oxidation
      of most organic substrates to the one-electron transfers of the respiratory
      chain. In addition, they are now known as versatile compounds that can function
      as electrophiles and nucleophiles, with covalent intermediates of flavin and
      substrate frequently being involved in catalysis. Flavins are thought to
      contribute to oxidative stress through their ability to produce superoxide, but
      at the same time flavins are frequently involved in the reduction of
      hydroperoxides, products of oxygen-derived radical reactions. Flavoproteins play
      an important role in soil detoxification processes via the hydroxylation of many
      aromatic compounds, and a simple flavoprotein in liver microsomes catalyses many
      reactions similar to those carried out by cytochrome P450 enzymes. Flavins are
      involved in the production of light in bioluminescent bacteria, and are
      intimately connected with light-initiated reactions such as plant phototropism
      and nucleic acid repair processes. Recent reports also link them to programmed
      cell death. The chemical versatility of flavoproteins is clearly controlled by
      specific interactions with the proteins with which they are bound. One of the
      main thrusts of current research is to try to define the nature of these
      interactions, and to understand in chemical terms the various steps involved in
      catalysis by flavoprotein enzymes.

PMID- 10961911
TI  - Multicolor FISH analysis of chromosomal breaks, duplications, deletions, and
      numerical abnormalities in the sperm of healthy men.
AB  - Transmitted de novo structural chromosomal abnormalities, the majority of which
      are paternally derived, can lead to abnormal reproductive outcomes as well as
      genetic diseases in offspring. We developed and validated a new multicolor FISH
      procedure (sperm ACM, which utilizes DNA probes specific for the alpha [1cen],
      classical, [1q12], and midi [1p36.3] satellites of chromosome 1) which utilizes
      DNA probes specific for three regions of chromosome 1 to detect human sperm that
      carry numerical abnormalities plus two categories of structural aberrations: (1)
      duplications and deletions of 1pter and 1cen, and (2) chromosomal breaks within
      the 1cen-1q12 region. In healthy men, the average frequencies of sperm with
      duplications and deletions were (a) 4.5 +/- 0.5 and 4.1 +/- 1.3 per 10(4)
      involving 1pter and (b) 0.9 +/- 0.4 and 0.8 +/- 0.3 per 10(4) involving 1cen,
      respectively. The frequency of sperm exhibiting breaks within the 1cen-1q12
      region was 14.1 +/- 1.2 per 10(4). Structural aberrations accounted for 71% of
      the abnormalities detected by sperm ACM, which was significantly higher than
      numerical abnormalities (P=2x10-8). Our findings also suggest that, for healthy
      men, (a) sperm carrying postmeiotic chromosomal breaks appear to be more
      prevalent than those carrying products of premeiotic or meiotic breakage or
      rearrangements, (b) the high frequency of chromosome breaks measured after
      "fertilization" by the hamster-egg cytogenetic method already appear to be
      present and detectable within human sperm by FISH, and (c) there are nonrandom
      and donor-specific distributions of breakpoint locations within 1q12 in sperm.
      FISH facilitates the analysis of much larger numbers of sperm than was possible
      when the hamster-egg method was used. Therefore, FISH-based procedures for
      simultaneously detecting chromosomal breaks, rearrangements, and numerical
      abnormalities in sperm may have widespread applications in human genetics,
      genetic toxicology, and reproductive medicine.

PMID- 10961913
TI  - l-glutamate as a central neurotransmitter: looking back.
AB  - The high concentration in brain of unbound l-glutamic acid (in its anionic form,
      l-glutamate) fuelled considerable speculation as to its role in central nervous
      function more than 50 years ago. Claims in the 1940s that it could improve
      cognitive acuity in patients with mental impairment were particularly intriguing,
      though later refuted. In the early 1950s Hayashi [(1954) Keio J. Med. 3, 183-192]
      found that l-glutamate could cause convulsions and proposed that it might be a
      central synaptic transmitter. Soon thereafter, Curtis and colleagues [Curtis,
      Phillis and Watkins (1959) Nature (London) 183, 611] showed that l-glutamate
      depolarized and excited central neurons, as expected for an excitatory
      transmitter; however, various aspects of the action of l-glutamate seemed to
      argue strongly against a transmitter function. This negative view prevailed for
      some 20 years, before compelling evidence for such a role was adduced. Over the
      last two decades, extensive research has revealed a host of glutamate receptor
      subtypes, subserving several different functions in excitatory synaptic
      transmission. This paper gives a very brief and personal overview of the
      development of the field over the last 50 years from a mainly pharmacological
      standpoint.

PMID- 10961914
TI  - Integrin structure.
AB  - The integrins are a family of alpha,beta heterodimeric receptors that mediate
      dynamic linkages between extracellular adhesion molecules and the intracellular
      actin cytoskeleton. Integrins are expressed by all multicellular animals, but
      their diversity varies widely among species; for example, in mammals, 19 alpha
      and 8 beta subunit genes encode polypeptides that combine to form 25 different
      receptors, whereas the Drosophila and Caenorhabditis genomes encode only five and
      two integrin alpha subunits respectively. Thousands of studies over the last two
      decades have investigated the molecular, cellular and organismal basis of
      integrin function. Gene deletion has demonstrated essential roles for almost all
      integrins, with the defects suggesting widespread contributions to both the
      maintenance of tissue integrity and the promotion of cellular migration. Integrin
      ligand interactions are now considered to provide physical support for cells in
      order to maintain cohesion, to permit the generation of traction forces to enable
      movement, and to organize signalling complexes to modulate differentiation and
      cell fate. Animal-model studies have also shown that integrins contribute to the
      progression of many common diseases, and have implicated them as potential
      therapeutic targets. The use of anti-integrin monoclonal antibodies and ligand
      mimetic peptides has validated this suggestion for inflammatory, neoplastic,
      traumatic and infectious conditions. Thus, to understand more about the
      mechanisms underlying tissue organization and cellular trafficking, and to
      identify approaches for regulating these processes in disease, there is intense
      interest in determining the molecular basis of integrin function. It is important
      to state at the outset that the tertiary structure of the integrin dimer is
      unknown. Our current understanding of the molecular basis of integrin function is
      therefore compiled from the results of a large number of studies that have
      employed a wide range of complementary technologies.

PMID- 10961915
TI  - Potential use of stem cells from bone marrow to repair the extracellular matrix
      and the central nervous system.
AB  - A subset of stem-like cells from bone marrow that are referred to as marrow
      stromal cells (MSCs) have been shown to be capable of differentiating into
      osteoblasts, chondrocytes, adipocytes, myocytes, astrocytes and perhaps neurons.
      Recently, conditions have been developed where human MSCs can be expanded almost
      without limit in culture without apparently losing their multipotentiality for
      differentiation. The cells appear to be potentially useful for the repair of
      extracellular matrix and the central nervous system.

PMID- 10961916
TI  - Morphogenetic messages are in the extracellular matrix: biotechnology from bench
      to bedside.
AB  - The origin and evolution of multicellular metazoa was accompanied by the
      appearance of extracellular matrix. The demineralized extracellular matrix of
      bone is enriched in morphogenetic proteins that induce bone. Bone morphogenetic
      proteins (BMPs) are intimately bound to collagens. BMP-4 has high affinity for
      type-IV collagen, and other binding proteins such as noggin and chordin. Soluble
      morphogens are kept in the solid state by extracellular matrix. In this sense
      Nature used the principles of affinity matrices long before humans patented the
      principle of affinity chromatography.

PMID- 10961917
TI  - Recombinant expression systems for the production of collagen.
AB  - The ability of triple-helical collagen molecules to assemble into supramolecular
      structures forms the basis of commercial uses of collagen in the food industry
      and in medical applications such as cosmetic surgery and tissue repair. We have
      used cDNA techniques to engineer novel collagens with potentially enhanced
      biological properties; however, expression of fully functional novel molecules is
      difficult due to the complex nature of procollagen biosynthesis. This article
      outlines the application of various expression systems to procollagen production
      and details the use of the mammary gland as a suitable bioreactor for the
      synthesis of significant amounts of novel procollagens from cDNA constructs.

PMID- 10961918
TI  - Expression of recombinant human type I-III collagens in the yeast pichia
      pastoris.
AB  - An efficient expression system for recombinant human collagens will have numerous
      scientific and medical applications. However, most recombinant systems are
      unsuitable for this purpose, as they do not have sufficient prolyl 4-hydroxylase
      activity. We have developed methods for producing the three major fibril-forming
      human collagens, types I, II and III, in the methylotrophic yeast Pichia
      pastoris. These methods are based on co-expression of procollagen polypeptide
      chains with the alpha- and beta-subunits of prolyl 4-hydroxylase. The triple
      helical type-I, -II and-III procollagens were found to accumulate predominantly
      within the endoplasmic reticulum of the yeast cells and could be purified from
      the cell lysates by a procedure that included a pepsin treatment to convert the
      procollagens into collagens and to digest most of the non-collagenous proteins.
      All the purified recombinant collagens were identical in 4-hydroxyproline content
      with the corresponding non-recombinant human proteins, and all the recombinant
      collagens formed native-type fibrils. The expression levels using single-copy
      integrants and a 2 litre bioreactor ranged from 0.2 to 0.6 g/l depending on the
      collagen type.

PMID- 10961919
TI  - Towards a fibrous composite with dynamically controlled stiffness: lessons from
      echinoderms.
AB  - Sea urchins and sea cucumbers, like other echinoderms, control the tensile
      properties of their connective tissues by regulating stress transfer between
      collagen fibrils. The collagen fibrils are spindle-shaped and up to 1 mm long
      with a constant aspect ratio of approx. 2000. They are organized into a tissue by
      an elastomeric network of fibrillin microfibrils. Interactions between the
      fibrils are regulated by soluble macromolecules that are secreted by local,
      neurally controlled, effector cells. We are characterizing the non-linear
      viscoelastic properties of sea cucumber dermis under different conditions, as
      well as the structures, molecules and molecular interactions that determine its
      properties. In addition, we are developing reagents that will bind covalently to
      fibril surfaces and reversibly form cross-links with other reagents, resulting in
      a chemically controlled stress-transfer capacity. The information being developed
      will lead to the design and construction of a synthetic analogue composed of
      fibres in an elastomeric matrix that contains photo- or electro-sensitive
      reagents that reversibly form interfibrillar cross-links.

PMID- 10961920
TI  - Inductive activity of recombinant human growth and differentiation factor-5.
AB  - Growth and differentiation factor-5 (GDF-5) is a divergent member of the
      transforming growth factor-beta/bone morphogenetic protein (BMP) superfamily that
      is required for proper skeletal patterning and development in the vertebrate
      limb. Based on the homology of GDF-5 with other bone-inducing BMP family members,
      the inductive activity of a recombinant form of human GDF-5 (rhGDF-5) was
      evaluated in a series of in vitro assays and in vivo bone-formation models. The
      in vitro response to rhGDF-5 resulted in the formation of chondrogenic nodules in
      fetal rat calvarial cells cultured in the context of collagen or
      collagen/hyaluronate extracellular matrices. Matrices loaded with rhGDF-5 induced
      ectopic cartilaginous and osseous tissue when implanted in subcutaneous or
      intramuscular sites. In non-human primate long-bone-defect and spinal-fusion
      models, rhGDF-5 combined with a mineralized collagen matrix induced bone
      formation in a manner equivalent to autogenous bone. These results highlight the
      unique potential of rhGDF-5 in a wide variety of orthopaedic applications.

PMID- 10961921
TI  - Gene regulation through chromatin remodelling by members of the nuclear receptor
      superfamily.
AB  - The intracellular receptors for steroid hormones, thyroid hormones, retinoids and
      vitamin D(3) are known to bind to specific DNA elements and thus regulate target
      gene expression. This introductory review and the following papers address some
      of the mechanisms underlying this action. In particular, the ability of this
      family of transcription factors to recruit multi-protein complexes that have the
      capacity to remodel chromatin structure in order to silence or activate target
      gene expression is discussed.

PMID- 10961922
TI  - Helical repeat of DNA in the nucleosome core particle.
AB  - Although the crystal structure of nucleosome core particle is essentially
      symmetrical in the vicinity of the dyad, the linker histone binds asymmetrically
      in this region to select a single high-affinity site from potentially two
      equivalent sites. To try to resolve this apparent paradox we mapped to base-pair
      resolution the dyads and rotational settings of nucleosome core particles
      reassembled on synthetic tandemly repeating 20 bp DNA sequences. In agreement
      with previous observations, we observed (1) that the helical repeat on each side
      of the dyad cluster is 10 bp maintaining register with the sequence repeat and
      (2) that this register changes by 2 bp in the vicinity of the dyad. The
      additional 2 bp required to effect the change in the rotational settings is
      accommodated by an adjustment immediately adjacent to the dyad. At the dyad the
      hydroxyl radical cleavage is asymmetric and we suggest that the inferred
      structural asymmetry could direct the binding of the linker histone to a single
      preferred site.

PMID- 10961923
TI  - Mechanisms for ATP-dependent chromatin remodelling.
AB  - Gene regulation involves the generation of a local chromatin topology that is
      conducive to transcription. Several classes of chromatin remodelling activity
      have been shown to play a role in this process. ATP-dependent chromatin
      remodelling activities use energy derived from the hydrolysis of ATP to alter the
      structure of chromatin, making it more accessible for transcription factor
      binding. The yeast SWI-SWF complex is the founding member of this family of ATP
      dependent chromatin-remodelling activities. We have developed a model system to
      study the ability of the SWI-SWF complex to alter chromatin structure. Using this
      system, we find that SWI-SWF is able to alter the position of nucleosomes along
      the DNA. This is consistent with recent reports that other ATP-dependent
      chromatin-remodelling activities can alter the positions of nucleosomes along
      DNA. This suggests that nucleosome mobilization may be a general feature of the
      activity of ATP-dependent chromatin-remodelling activities. Some of the
      mechanisms by which nucleosomes may be moved along DNA are discussed.

PMID- 10961924
TI  - Co-repressor complexes and remodelling chromatin for repression.
AB  - Recent progress identifies targeted chromatin remodelling by co-repressor
      complexes as being an integral component of transcriptional silencing. Here we
      discuss how chromatin structure and the basal transcriptional machinery are
      manipulated by the co-repressor complex containing the Mi-2 nucleosomal ATPase,
      the histone-binding protein RbAp48 and histone deacetylase and by the co
      repressor complex containing SIN3, RbAp48 and histone deacetylase. Remarkably,
      both of these complexes also contain methyl-CpG-binding proteins. This
      observation provides a molecular mechanism to integrate DNA methylation fully
      into gene control in vertebrates.

PMID- 10961925
TI  - Modulation of thyroid hormone receptor silencing function by co-repressors and a
      synergizing transcription factor.
AB  - We have found that the thyroid hormone receptor (T3R) functionally synergizes
      with the CCCTC-binding factor (CTCF). CTCF is a highly conserved zinc-finger
      protein that has been connected with multiple functions in gene regulation
      including chromatin insulator activity, transcriptional enhancement and silencing
      as well as tumour suppression. A specific property of CTCF is that some of the
      binding sites are found in the vicinity of T3R-binding sites. Interestingly, both
      factors synergize in repression as well as in activation. T3R-mediated repression
      has been shown to involve co-repressors such as the silencing mediator for
      retinoic acid and thyroid hormone receptor (SMRT), N-CoR or Alien. These co
      repressors in turn have been found to interact with Sin3A. Until now, the
      mechanisms by which CTCF synergizes with T3R in transcriptional repression has
      not been determined. Here we show that CTCF comprises autonomous silencing
      domains that mediate transcriptional repression when tethered to a promoter
      sequence. At least one of these domains, the zinc-finger region of CTCF, binds
      Sin3A without binding to SMRT or N-CoR and recruits histone deacetylation
      activity. For Sin3A we identified two different domains interacting independently
      with the CTCF zinc-finger cluster. The ability of regions of CTCF to retain
      deacetylase activity is correlated with the ability to bind to Sin3A and to
      repress transcription. Taking these results together, the synergy in repression
      mediated by T3R and CTCF might be achieved by the binding of multiple molecules
      of Sin3A to the T3R/CTCF-DNA complex, thus providing a large platform for the
      recruitment of histone deacetylases.

PMID- 10961926
TI  - Transcriptional repression by nuclear receptors: mechanisms and role in disease.
AB  - Co-repressor proteins mediate transcriptional repression by nuclear receptors in
      the absence of ligand. The identification of a co-repressor-receptor interaction
      motif, and the finding that co-repressors and co-activators compete for the same
      site on the receptor, suggests a simple mechanism for the switch from repression
      to activation upon ligand binding. Defects in this mechanism result in dominant
      negative receptors that repress transcription. Such receptors have been
      implicated in several clinically important diseases, including thyroid hormone
      resistance and diabetes mellitus.

PMID- 10961927
TI  - Structural aspects of agonism and antagonism in the oestrogen receptor.
AB  - We have determined the three-dimensional structures of both alpha- and beta-forms
      of the ligand-binding domain of the oestrogen receptor (ER) in complexes with a
      range of receptor agonists and antagonists. Here, we summarize how these
      structures provide both an understanding of the ER's distinctive pharmacophore
      and a rationale for its ability to bind a diverse range of chemically distinct
      compounds. In addition, these studies provide a unique insight into the
      mechanisms that underlie receptor activation, as well as providing a structural
      basis for the antagonist action of molecules, such as raloxifene.

PMID- 10961928
TI  - Androgen-receptor-interacting nuclear proteins.
AB  - Androgen receptor (AR) belongs to the superfamily of nuclear hormone receptors
      that employ complex molecular mechanisms to guide the development and
      physiological functions of their target tissues. Our recent work has led to the
      identification of four novel proteins that recognize AR zinc-finger region (ZFR)
      both in vivo and in vitro. One is a small nuclear RING-finger protein that
      possesses separate interaction interfaces for AR and for other transcription
      activators such as Sp1. The second is a nuclear serine/threonine protein kinase
      (androgen-receptor-interacting nuclear protein kinase; ANPK); however, the
      receptor itself does not seem to be a substrate for this kinase. The third one is
      dubbed androgen-receptor-interacting protein 3 (ARIP3) and is a novel member of
      the PIAS (protein inhibitor of activated STAT) protein family. The fourth
      protein, termed ARIP4, is a nuclear ATPase that belongs to the SNF2-like family
      of chromatin remodelling proteins. All four proteins exhibit a punctate nuclear
      pattern when expressed in cultured cells. Each protein modulates AR-dependent
      transactivation in co-transfection experiments; their activating functions are
      not restricted to AR. Current work is aimed at elucidating the biochemical and
      functional properties of these AR-interacting proteins and at finding the partner
      proteins that form complexes with them in vivo.

PMID- 10961929
TI  - Dynamics of gene targeting and chromatin remodelling by nuclear receptors.
AB  - Activation of the murine-mammary-tumour virus (MMTV) promoter by the
      glucocorticoid receptor (GR) is associated with a chromatin structural transition
      in the B nucleosome region of the viral long terminal repeat (LTR). We have
      reconstituted this nucleoprotein transition with chromatin assembled on MMTV LTR
      DNA with Drosophila embryo extracts, purified GR, and HeLa nuclear extract.
      Chromatin remodelling in vitro is ATP-dependent and maps to a region identical
      with that found in vivo. We demonstrate specific, glucocorticoid response element
      dependent, binding of purified GR to a large, multi-nucleosome MMTV chromatin
      array and show that GR-dependent chromatin remodelling is a multistep process. In
      the absence of ATP, GR binds to multiple sites on the chromatin array and
      inhibits nuclease access to GR recognition sites. On the addition of ATP, GR
      induces remodelling resulting in a large increase in access of enzymes to their
      sites within the transition region. These findings are complemented by studies in
      living cells; using a tandem array of MMTV-Ras reporter elements and a form of GR
      labelled with the green fluorescent protein, we have observed direct targeting of
      the receptor to response elements in live mouse cells. Whereas the ligand
      activated receptor is associated with the MMTV promoter for observable periods,
      photobleaching experiments provide direct evidence that the hormone-occupied
      receptor undergoes rapid exchange between chromatin and the nucleoplasmic
      compartment. The results both in vitro and in vivo are consistent with a dynamic
      model ('hit and run') in which GR first binds to chromatin after ligand
      activation, recruits a remodelling activity and is then lost from the template.

PMID- 10961930
TI  - Recruitment of chromatin remodelling factors during gene activation via the
      glucocorticoid receptor N-terminal domain.
AB  - We have shown that yeast mutants with defects in the Ada adaptor proteins are
      defective in hormone-dependent gene activation by ectopically expressed human
      glucocorticoid receptor (GR). Others have shown that the Ada2 protein is required
      for physical interactions between some activation domains and TBP (TATA-binding
      protein), whereas the Gcn5 (Ada4) protein has a histone acetyltransferase (HAT)
      activity. Although all HAT enzymes are able to acetylate histone substrates, some
      also acetylate non-histone proteins. Taken together, these observations suggest
      that the Ada proteins have the ability to effect different steps in the process
      of gene activation. It has recently been shown that the Ada proteins are present
      in two distinct protein complexes, the Ada complex and a larger SAGA complex. Our
      recent work has focused on determining (1) which of the Ada-containing complexes
      mediates gene activation by GR, (2) whether the HAT activity encoded by GCN5 is
      required for GR-dependent gene activation, (3) whether the Ada proteins
      contribute to GR-mediated activation at the level of chromatin remodelling and
      (4) how the role of these HAT complexes is integrated with other chromatin
      remodelling activities during GR-mediated gene activation. Our results suggest a
      model in which GR recruits the SAGA complex and that this contributes to
      chromatin remodelling via a mechanism involving the acetylation of histones.
      Furthermore, recruitment of the SWI/SNF remodelling complex also has a role in GR
      mediated activation that is independent of the role of SAGA. These complexes are
      similar to analogous mammalian complexes and therefore these results are likely
      to be relevant to the human system.

PMID- 10961931
TI  - Co-operation between protein-acetylating and protein-methylating co-activators in
      transcriptional activation.
AB  - Nuclear hormone receptors (NRs) activate transcription by binding to specific
      enhancer elements associated with target genes. Transcriptional activation is
      accomplished with the help of complexes of co-activator proteins that bind to
      NRs. p160 co-activators, a family of three related 160 kDa proteins, serve as
      primary co-activators by binding directly to NRs and recruiting additional
      secondary co-activators. Some of these (CBP/p300 and p/CAF) can acetylate
      histones and other proteins in the transcription complex, thus helping to modify
      chromatin structure and form an active transcription initiation complex. We
      recently discovered co-activator-associated arginine methyltransferase 1 (CARM1),
      which binds to p160 co-activators and thereby enhances transcriptional activation
      by NRs on transiently transfected reporter genes. CARM1 also methylates specific
      arginine residues in the N-terminal tail of histone H3 in vitro. A related
      arginine-specific protein methyltransferase, PRMT1, also binds p160 co-activators
      and enhances NR function. PRMT1 methylates histone H4 in vitro. The enhancement
      of NR function by CARM1, PRMT1 and p300 depends on their interactions with p160
      co-activators. In the presence of p160 co-activators, some pairs of these three
      secondary co-activators provide a highly synergistic enhancement of NR function
      on transiently transfected reporter genes. We have also observed an enhancement
      of NR function on stably integrated reporter genes by these co-activators. We
      propose that the synergy of co-activator function between p300, CARM1 and PRMT1
      is due to their different but complementary protein modification activities.

PMID- 10961932
TI  - Mechanisms of initiation and termination of signalling by neuropeptide receptors:
      a comparison with the proteinase-activated receptors.
AB  - Biological responses to neuropeptides are rapidly attenuated by overlapping
      mechanisms that include peptide degradation by cell-surface proteases, receptor
      uncoupling from heterotrimeric G-proteins and receptor endocytosis. We have
      investigated the mechanisms that terminate the proinflammatory effects of the
      neuropeptide substance P (SP), which are mediated by the neurokinin 1 receptor
      (NK1R). Neutral endopeptidase degrades SP in the extracellular fluid and is one
      of the first mechanisms to terminate signalling. G-protein receptor kinases and
      second-messenger kinases phosphorylate the NK1R to permit interaction with beta
      arrestins, which uncouple the receptor from G-proteins to terminate the signal.
      SP-induces NK1R endocytosis by a beta-arrestin-dependent mechanism, which also
      involves the GTPases dynamin and Rab5a. Endocytosis contributes to
      desensitization by depleting receptors from the cell surface. Disruption of these
      mechanisms results in uncontrolled stimulation and disease. Thus the deletion of
      neutral endopeptidase in mice exacerbates inflammation of many tissues. There are
      similarities and distinct differences in the mechanisms that regulate signalling
      by neuropeptide receptors and other G-protein-coupled receptors, in particular
      those that are activated irreversibly by proteolysis.

PMID- 10961933
TI  - Endothelin-converting enzyme-like 1 (ECEL1; 'XCE'): a putative metallopeptidase
      crucially involved in the nervous control of respiration.
AB  - Endothelin-converting enzyme-like 1 (ECEL1) is a putative zinc metalloprotease
      that was recently identified on the basis of its strong similarity to endothelin
      converting enzyme 1. The physiological function of ECEL1 remains unknown so far;
      the failure to identify a substrate for ECEL1 could be related to the endoplasmic
      reticulum subcellular localization found by immunofluorescence in recombinant
      systems. However, clues to the function of ECEL1 were provided by the
      inactivation of its gene in mice, which resulted in neonatal lethality. The
      phenotype of homozygous ECEL1(-/-) mice, together with the very specific
      expression profile of its mRNA in the central nervous system, suggests that ECEL1
      is crucially involved in the nervous control of respiration.

PMID- 10961934
TI  - Neuropeptidases regulating gonadal function.
AB  - The generation and metabolism of bioactive peptides involves a series of highly
      ordered proteolytic events. This post-translational processing can occur either
      within the cell, at the cell surface or after secretion. In the central nervous
      system a number of extracellular peptidases have been implicated in the regulated
      processing of peptides, particularly in the regulation of neuroendocrine
      function. The aim of this study has been to identify the peptidases involved in
      the metabolism of gonadotropin-releasing hormone (GnRH) and to characterize the
      factors and the mechanisms by which the activity of these peptidases are
      regulated. We have shown that both prolylendopeptidase and the thimet
      oligopeptidase EC 3.4. 24.15 are involved in GnRH metabolism and that both
      oestrogen and thiol-based reductants could be involved in the physiological
      regulation of their activities.

PMID- 10961935
TI  - Aminopeptidase A, which generates one of the main effector peptides of the brain
      renin-angiotensin system, angiotensin III, has a key role in central control of
      arterial blood pressure.
AB  - Overactivity of the brain renin-angiotensin system (RAS) has been implicated in
      the development and maintenance of hypertension in several experimental animal
      models. We have recently reported that, in the murine brain RAS, angiotensin II
      (AngII) is converted by aminopeptidase A (APA) into angiotensin III
      (AngIII),which is itself degraded by aminopeptidase N (APN), both peptides being
      equipotent to increase vasopressin release and arterial blood pressure when
      injected by the intracerebroventricular (i.c.v.) route. Because AngII is
      converted in vivo into AngIII, the exact nature of the active peptide is not
      precisely known. To delineate their respective roles in the central control of
      cardiovascular functions, specific and selective APA and APN inhibitors are
      needed to block the metabolic pathways of AngII and AngIII respectively. In the
      absence of such compounds for APA, we first explored the organization of the APA
      active site by site-directed mutagenesis. This led us to propose a molecular
      mechanism of action for APA similar to that proposed for the bacterial enzyme
      thermolysin deduced from X-ray diffraction studies. Secondly, we developed a
      specific and selective APA inhibitor, compound EC33 [(S)-3-amino-4
      mercaptobutylsulphonic acid], as well as a potent and selective APN inhibitor,
      PC18 (2-amino-4-methylsulphonylbutane thiol). With these new tools we examined
      the respective roles of AngII and AngIII in the central control of arterial blood
      pressure. A central blockade of APA with the APA inhibitor EC33 suppressed the
      pressor effect of exogenous AngII, suggesting that brain AngII must be converted
      into AngIII to increase arterial blood pressure. Furthermore, EC33, injected
      alone i.c.v. but not intravenously, caused a dose-dependent decrease in arterial
      blood pressure by blocking the formation of brain AngIII but not systemic AngIII.
      This is corroborated by the fact that the selective APN inhibitor PC18
      administered alone via the i.c.v. route increased arterial blood pressure. This
      pressor response was blocked by prior treatment with the angiotensin type 1
      receptor antagonist losartan, showing that blocking the action of APN on AngIII
      metabolism leads to an increase in endogenous AngIII levels, resulting in
      arterial blood pressure increase through an interaction with angiotensin type 1
      receptors. These results demonstrate that AngIII is a major effector peptide of
      the brain RAS, exerting a tonic stimulatory control over arterial blood pressure.
      Thus APA, the enzyme responsible for the formation of brain AngIII, represents a
      potential central therapeutic target that justifies the development of APA
      inhibitors, crossing the blood-brain barrier, as central anti-hypertensive
      agents.

PMID- 10961936
TI  - Protein processing mechanisms: from angiotensin-converting enzyme to Alzheimer's
      disease.
AB  - Angiotensin-converting enzyme (ACE) and the Alzheimer's disease amyloid precursor
      protein are two examples of membrane-bound proteins that are released in a
      soluble form by a post-translational proteolytic cleavage event involving a
      secretase. Site-specific antibodies and matrix-assisted laser desorption
      ionization-time-of-flight ('MALDI-TOF') MS have been used to map the secretase
      cleavage site in somatic ACE to Arg-1203/Ser-1204, 24 residues proximal to the
      membrane-anchoring domain. Trypsin, which can solubilize ACE from the membrane,
      cleaves the protein at the same site. The use of structurally related hydroxamic
      acid-based zinc metalloproteinase inhibitors indicate that tumour necrosis factor
      alpha convertase, a member of the ADAMs ('a disintegrin and metalloproteinase')
      family of proteins, is not involved in the proteolytic release of ACE, or in the
      constitutive or regulated alpha-secretase release of the amyloid precursor
      protein from a human neuronal cell line.

PMID- 10961937
TI  - Complexity of transcriptional control in neuropeptide gene expression; enkephalin
      gene regulation during neurodevelopment.
AB  - The gene for enkephalin is expressed only in specific subsets of neurons in the
      mammalian central nervous system (CNS), whereas the large majority of neurons do
      not express the gene. This restricted expression is the result of a developmental
      process during which some of the multipotent neural progenitors express the gene
      for enkephalin and thereby become enkephalinergic neurons. The regulation of this
      process is not well understood. We have used a novel approach to identify DNA
      protein interactions that regulate the developmental expression of the gene for
      enkephalin. We have identified four novel DNA regulatory sites and their binding
      proteins that are expressed in the developing mammalian CNS. These protein-DNA
      interactions regulate DNA and nuclear structures through DNA bending, DNA
      sliding, chromatin remodelling and far-distant DNA interactions. The concerted
      and co-ordinated interactions of these four DNA elements and their binding
      proteins contribute to the guiding of multipotent neural progenitors into
      enkephalinergic neurons. The provided examples suggest an important role for
      architectural transcriptional regulation during CNS development.

PMID- 10961938
TI  - Protective peptides derived from novel glial proteins.
AB  - In studying the mediators of VIP neurotrophism in the central nervous system, two
      glial proteins have been discovered. Both of these proteins contain short
      peptides that exhibit femtomolar potency in preventing neuronal cell death from a
      wide variety of neurotoxic substances. Extension of these peptides to models of
      oxidative stress or neurodegeneration in vivo have indicated significant efficacy
      in protection. These peptides, both as individual agents and in combination, have
      promise as possible protective agents in the treatment of human neurodegenerative
      disease and in pathologies involving oxidative stress.

PMID- 10961939
TI  - Phosphinic peptide inhibitors as tools in the study of the function of zinc
      metallopeptidases.
AB  - The development of the combinatorial chemistry of phosphinic peptides has led to
      the discovery of both highly potent and selective inhibitors of various zinc
      metalloproteinases. Several properties of these compounds are reviewed,
      supporting the view that this class of inhibitors should represent useful tools
      for probing several aspects of the function of this broad family of proteases in
      vivo.

PMID- 10961940
TI  - Conserved roles for peptidases in the processing of invertebrate neuropeptides.
AB  - Invertebrates use a wide range of peptides as transmitters and hormones to
      regulate complex behaviour, physiology and development. These animals, especially
      those that are amenable to genetic study and are the subject of genome-sequencing
      projects, provide powerful model systems for understanding the functions of
      peptidases in controlling the bioactivity of peptides. Neprilysin, a zinc
      metallopeptidase and a key enzyme in the metabolism of mammalian peptides, is
      also implicated in the inactivation of peptides at synapses and of circulating
      peptide hormones in insects and nematodes. A family of neprilysin-like genes are
      present in the genomes of both Drosophila melanogaster and Caenorhabditis
      elegans; in C. elegans it seems that individual family members have evolved to
      take on different physiological functions, because they are expressed in a tissue
      specific manner. Angiotensin I-converting enzymes (peptidyl dipeptidase A,
      angiotensin-converting enzyme) are another group of zinc metallopeptidases found
      in some invertebrates that lack angiotensin peptides. In D. melanogaster there
      are two functional angiotensin-converting enzymes that are essential for normal
      development. One of these (Acer) is expressed in the embryonic heart, whereas the
      second enzyme (Ance) is expressed in several tissues at different stages of the
      life cycle. The accumulation of Ance within secretory vesicles of some peptide
      synthesizing cells suggests a role for the enzyme in the intracellular processing
      of insect peptides. Ance is very efficient at cleaving pairs of basic residues
      from the C-terminus of partly processed peptides, suggesting a novel role for the
      enzyme in prohormone processing. Invertebrates will continue to provide insights
      into the evolutionarily conserved functions of known peptidases and of those
      additional family members that are expected to be identified in the future from
      genome-sequencing projects.

PMID- 10961941
TI  - Exploring the Caenorhabditis elegans and Drosophila melanogaster genomes to
      understand neuropeptide and peptidase function.
AB  - Comparison of peptidase gene families in the newly released Drosophila
      melanogaster and Caenorhabditis elegans genomes highlights important differences
      in peptidase distributions with relevance to the evolution of both form and
      function in these two organisms and can help to identify the most appropriate
      model when using comparative studies relevant to the human condition.

PMID- 10961943
TI  - Ca2+signalling in stomatal guard cells.
AB  - Ca(2+) is a ubiquitous second messenger in the signal transduction pathway(s) by
      which stomatal guard cells respond to external stimuli. Increases in guard-cell
      cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) have been observed in
      response to stimuli that cause both stomatal opening and closure. In addition,
      several important components of Ca(2+)-based signalling pathways have been
      identified in guard cells, including the cADP-ribose and phospholipase C/Ins(1,
      4,5)P(3)-mediated Ca(2+)-mobilizing pathways. The central role of stimulus
      induced increases in [Ca(2+)](cyt) in guard-cell signal transduction has been
      clearly demonstrated in experiments examining the effects of modulating increases
      in [Ca(2+)](cyt) on alterations in guard-cell turgor or the activity of ion
      channels that act as effectors in the guard-cell turgor response. In addition,
      the paradox that Ca(2+) is involved in the transduction of signals that result in
      opposite end responses (stomatal opening and closure) might be accounted for by
      the generation of stimulus-specific Ca(2+) signatures, such that increases in
      [Ca(2+)](cyt) exhibit unique spatial and temporal characteristics.

PMID- 10961942
TI  - Cyclic-nucleotide- and Ca2+/calmodulin-regulated channels in plants: targets for
      manipulating heavy-metal tolerance, and possible physiological roles.
AB  - Recently we discovered a tobacco protein (designated NtCBP4) that modulates heavy
      metal tolerance in transgenic plants. Structurally, NtCBP4 is similar to
      mammalian cyclic-nucleotide-gated non-selective cation channels containing six
      putative transmembrane domains, a predicted pore region, a conserved cyclic
      nucleotide-binding domain, and a high-affinity calmodulin-binding site that
      coincides with its cyclic-nucleotide-binding domain. Transgenic tobacco
      expressing the plasma-membrane-localized NtCBP4 exhibit improved tolerance to
      Ni(2+) and hypersensitivity to Pb(2+), which are associated with a decreased
      accumulation of Ni(2+) and an enhanced accumulation of Pb(2+) respectively.
      Transgenic plants expressing a truncated version of NtCBP4, from which regulatory
      domains had been removed, have a different phenotype. Here we describe our
      approach to studying the involvement of NtCBP4 in heavy-metal tolerance and to
      elucidate its physiological role.

PMID- 10961944
TI  - Auxin transport: providing a sense of direction during plant development.
AB  - Auxins are key regulators of plant development. Plants employ a specialized
      delivery system termed polar auxin transport to convey indole-3-acetic acid from
      source to target tissues. Auxin transport is mediated by the combined activities
      of specialized influx and efflux carriers. Mutational approaches in the model
      plant, Arabidopsis thaliana, have led to the molecular genetic characterization
      of putative auxin influx and efflux carrier components, AUX1 and AtPIN1. Both
      genes belong to distinct gene families that are being functionally characterized
      by using a reverse genetic approach in Arabidopsis. AtPIN proteins are
      asymmetrically localized within plant plasma membranes, providing a molecular
      mechanism for the characteristic polarity of auxin transport. We outline the
      epitope tagging strategy being used in our laboratory to immunolocalize AUX1 and
      discuss the implications of its subcellular localization for auxin redistribution
      within root apical tissues. Lastly, we describe a novel carrier-based mechanism
      that plant cells might use to determine their relative position(s) within an
      auxin gradient, drawing parallels with the mechanism of glucose perception in
      yeast.

PMID- 10961945
TI  - Mechanism of protein import across the chloroplast envelope.
AB  - The development and maintenance of chloroplasts relies on the contribution of
      protein subunits from both plastid and nuclear genomes. Most chloroplast proteins
      are encoded by nuclear genes and are post-translationally imported into the
      organelle across the double membrane of the chloroplast envelope. Protein import
      into the chloroplast consists of two essential elements: the specific recognition
      of the targeting signals (transit sequences) of cytoplasmic preproteins by
      receptors at the outer envelope membrane and the subsequent translocation of
      preproteins simultaneously across the double membrane of the envelope. These
      processes are mediated via the co-ordinate action of protein translocon complexes
      in the outer (Toc apparatus) and inner (Tic apparatus) envelope membranes.

PMID- 10961946
TI  - Novel mechanisms for the targeting of proteins into and across chloroplast
      membranes.
AB  - The assembly of the photosynthetic apparatus requires the translocation of
      numerous proteins from the cytosol, initially into the stroma and thereafter into
      or across the thylakoid membrane. Recent studies have shown that proteins are
      transported into this membrane by a variety of mechanisms, some of which are
      derived from a cyanobacterial-type ancestor, whereas others have evolved in
      response to the more complex transport pathway used by cytosolically synthesized
      chloroplast proteins. It is now apparent that some of the targeting pathways are
      used exclusively by hydrophobic thylakoid membrane proteins; here we review
      recent progress in our understanding of the biogenesis of this important class of
      protein.

PMID- 10961947
TI  - Membrane protein import in yeast mitochondria.
AB  - The protein import pathway that targets proteins to the mitochondrial matrix has
      been extensively characterized in the past 15 years. Variations of this import
      pathway account for the sorting of proteins to other compartments as well, but
      the insertion of integral inner membrane proteins lacking a presequence is
      mediated by distinct translocation machinery. This consists of a complex of Tim9
      and Tim10, two homologous, Zn(2+)-binding proteins that chaperone the passage of
      the hydrophobic precursor across the aqueous intermembrane space. The precursor
      is then targeted to another, inner-membrane-bound, complex of at least five
      subunits that facilitates insertion. Biochemical and genetic experiments have
      identified the key components of this process; we are now starting to understand
      the molecular mechanism. This review highlights recent advances in this new
      membrane protein insertion pathway.

PMID- 10961949
TI  - Organization of transport from endoplasmic reticulum to Golgi in higher plants.
AB  - In plant cells, the organization of the Golgi apparatus and its
      interrelationships with the endoplasmic reticulum differ from those in mammalian
      and yeast cells. Endoplasmic reticulum and Golgi apparatus can now be visualized
      in plant cells in vivo with green fluorescent protein (GFP) specifically directed
      to these compartments. This makes it possible to study the dynamics of the
      membrane transport between these two organelles in the living cells. The GFP
      approach, in conjunction with a considerable volume of data about proteins
      participating in the transport between endoplasmic reticulum and Golgi in yeast
      and mammalian cells and the identification of their putative plant homologues,
      should allow the establishment of an experimental model in which to test the
      involvement of the candidate proteins in plants. As a first step towards the
      development of such a system, we are using Sar1, a small G-protein necessary for
      vesicle budding from the endoplasmic reticulum. This work has demonstrated that
      the introduction of Sar1 mutants blocks the transport from endoplasmic reticulum
      to Golgi in vivo in tobacco leaf epidermal cells and has therefore confirmed the
      feasibility of this approach to test the function of other proteins that are
      presumably involved in this step of endomembrane trafficking in plant cells.

PMID- 10961948
TI  - Biochemical and molecular approaches to understanding protein import into
      peroxisomes.
AB  - Peroxisomes are eukaryotic organelles that perform diverse and variable
      functions. Although genetic studies in yeasts and mammals have identified
      approximately 20 genes (PEX genes) required for the biogenesis of this important
      organelle, biochemical studies of protein targeting and import have lagged behind
      and in many cases we have no idea of the function of the PEX gene products
      (peroxins). Using an import assay in vitro derived from sunflower cotyledon cells
      and recombinant proteins, we have obtained translocation intermediates on the
      peroxisome import pathway and are using cross-linking to identify interacting
      partners. We have also used antibodies raised against human PEX14 to inhibit the
      import of matrix proteins in this system. To obtain homologous antibodies for
      inhibition experiments, to immunoprecipitate cross-linked products and to enable
      us to study the import pathways of peroxins we have cloned and characterized
      plant orthologues of three PEX genes, PEX6, PEX10 and PEX14.

PMID- 10961950
TI  - Expression, purification and properties of multidrug efflux proteins.
AB  - A general strategy is described for the amplified expression, purification and
      characterization in Escherichia coli of multidrug efflux proteins from
      Staphylococcus aureus, Bacillus subtilis, Methanococcus janaschii and E. coli.
      They all catalyse drug/H(+) antiport of substrates such as quinolones and
      ethidium and exemplify a family of putatively 12-helix membrane proteins. The
      gene for each protein was cloned downstream of the tac promoter in plasmid
      pTTQ18; an oligonucleotide encoding six histidine residues was added, in frame,
      to the C-terminus to facilitate purification. Growth conditions were optimized in
      1-25-litre cultures of E. coli host strains to amplify the expression of each
      protein; the retention of activity was confirmed by assays of antibiotic
      resistance in vivo and/or assays of energized transport activity in vitro with
      synthetic substrates. Proteins were solubilized in dodecylmaltoside and purified
      to more than 90% homogeneity with Ni(2+)-nitrilotriacetate-affinity column
      chromography, yielding 5-25 mg per 25 litres of original culture. All the
      transport proteins migrated anomalously in SDS/PAGE at apparent molecular masses
      below those predicted from the gene sequence; identity and integrity were
      therefore confirmed by N-terminal amino acid sequencing and Western blotting for
      the C-terminal hexahistidine tag. Examination of the secondary structure of
      detergent-solubilized proteins by CD or Fourier-transform infrared spectroscopy
      following purification indicated a high content of alpha-helix (more than 75%).
      Matrix-assisted laser desorption ionization MS confirmed the high degree of
      purity and the true molecular mass. The formation of three-dimensional crystals
      is being attempted but crystals have yet to be grown that diffract X-rays. The
      growth of two-dimensional protein arrays has been more successful, with
      diffraction of electrons at low resolution. Proteins have been fused to green
      fluorescent protein or maltose-binding protein to facilitate these structural
      analyses. In addition, ligands for efflux proteins labelled with (13)C or (15)N
      have been synthesized to implement solid-state NMR studies of the ligand-binding
      site.

PMID- 10961951
TI  - Recognition of multiple drugs by a single protein: a trivial solution of an old
      paradox.
AB  - Multidrug-efflux transporters recognize scores of structurally dissimilar toxic
      compounds and expel them from cells. The broad chemical specificity of these
      transporters challenges some of the basic dogmas of biochemistry and remains
      unexplained. To understand, at least in principle, how a protein can recognize
      multiple compounds, we analysed the transcriptional regulator of the Bacillus
      subtilis multidrug transporter Bmr. This regulator, BmrR, binds multiple
      dissimilar hydrophobic cations and, by activating the expression of the Bmr
      transporter, causes their expulsion from the cell. Crystallographic analysis of
      the complexes of the inducer-binding domain of BmrR with some of its inducers
      revealed that ligands cause disordering of the surface alpha-helix and penetrate
      the hydrophobic core of the protein, where they form multiple van der Waals and
      stacking interactions with hydrophobic amino acids and an electrostatic bond with
      the buried glutamic residue. Mutational analysis of the binding site suggests
      that each ligand forms a unique set of atomic contacts with the protein: each
      tested mutation exerted disparate effects on the binding of different ligands.
      The example of BmrR demonstrates that a protein can bind multiple compounds with
      micromolar affinities by using only electrostatic and hydrophobic interactions.
      Its ligand specificity can be broadened by the flexibility of the binding site.
      It therefore seems that the commonly expressed fascination with the broad
      specificity of multidrug transporters is misdirected and originates from an
      almost exclusive familiarity with the more sophisticated processes of specific
      molecular recognition that predominate among existing proteins.

PMID- 10961952
TI  - Structure-function relationships in an anion-translocating ATPase.
AB  - The ArsAB ATPase is an efflux pump located in the inner membrane of Escherichia
      coli. This transport ATPase confers resistance to arsenite and antimonite by
      their extrusion from the cells. The pump is composed of two subunits, the
      catalytic ArsA subunit and the membrane subunit ArsB. The complex is similar in
      many ways to ATP-binding cassette ('ABC') transporters, which typically have two
      groups of six transmembrane-spanning helical segments and two nucleotide-binding
      domains (NBDs). The 45 kDa ArsB protein has 12 transmembrane-spanning segments.
      ArsB contains the substrate translocation pathway and is capable of functioning
      as an anion uniporter. The 63 kDa ArsA protein is a substrate-activated ATPase.
      It has two homologous halves, A1 and A2, which are clearly the result of an
      ancestral gene duplication and fusion. Each half has a consensus NBD. The
      mechanism of allosteric activation of the ArsA ATPase has been elucidated by a
      combination of molecular genetics and biochemical, structural and kinetic
      analyses. Conformational changes produced by binding of substrates, activator
      and/or products could be revealed by stopped-flow fluorescence measurements with
      single-tryptophan derivatives of ArsA. The results demonstrate that the rate
      limiting step in the overall reaction is a slow isomerization between two
      conformations of the enzyme. Allosteric activation increases the rate of this
      isomerization such that product release becomes rate-limiting, thus accelerating
      catalysis. ABC transporters, which exhibit similar substrate activation of ATPase
      activity, can undergo similar conformational changes to overcome a rate-limiting
      step. Thus the ArsAB pump is a useful model for elucidating mechanistic aspects
      of the ABC superfamily of transport ATPases.

PMID- 10961953
TI  - Therapeutic myocardial angiogenesis via vascular endothelial growth factor gene
      therapy: moving on down the road.

PMID- 10961954
TI  - Gaps in quality of cardiovascular care transcend social bias.

PMID- 10961955
TI  - The elusive link between LQT3 and Brugada syndrome: the role of flecainide
      challenge.
AB  - BACKGROUND: Defects of the SCN5A gene encoding the cardiac sodium channel are
      associated with both the LQT3 subtype of long-QT syndrome and Brugada syndrome
      (BS). The typical manifestations of long-QT syndrome (QT interval prolongation)
      and BS (ST segment elevation in leads V1 through V3) may coexist in the same
      patients, which raises questions about the actual differences between LQT3 and
      BS. Intravenous flecainide is the standard provocative test used to unmask BS in
      individuals with concealed forms of the disease, and oral flecainide has been
      proposed as a treatment option for LQT3 patients because it may shorten their QT
      interval. METHODS AND RESULTS: We tested the possibility that in some LQT3
      patients, flecainide might not only shorten the QT interval, but also produce an
      elevation of the ST segment. A total of 13 patients from 7 LQT3 families received
      intravenous flecainide using the protocol used for BS. As expected, QT, QTc, JT,
      and JTc interval shortening was observed in 12 of the 13 patients, and
      concomitant ST segment elevation in leads V1 through V3 (>/=2 mm) was observed in
      6 of the 13. CONCLUSIONS: The data demonstrate that flecainide may induce ST
      segment elevation in LQT3 patients, raising concerns about the safety of
      flecainide therapy and demonstrating the existence of an intriguing overlap
      between LQT3 and BS.

PMID- 10961956
TI  - Uptake of radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil
      in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase
      gene: the cellular basis for cardiac gene imaging.
AB  - BACKGROUND: Gene therapy is a promising approach for the treatment of cardiac
      diseases. Coexpression of therapeutic genes with a suitable marker gene would
      allow for the noninvasive imaging of successful gene transfer and expression via
      radiolabeled marker substrates. In the present study, such an approach was first
      applied to cardiac tissue. METHODS AND RESULTS: The combination of the
      herpesvirus thymidine kinase reporter gene (HSV1-tk) and radiolabeled 2'-fluoro
      2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat
      cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk
      containing adenovirus and a negative control virus. The intracellular uptake of
      [(14)C]FIAU increased with increasing multiplicity of infection and with time
      after infection. Uptake in negative controls remained <15% of positive controls.
      Additionally, vectors were applied intramyocardially in Wistar rats. The marker
      substrate [(125)I]FIAU was injected intravenously 3 days later, and animals were
      killed after 24 hours. Autoradiographically, regional transgene expression was
      clearly identified in animals receiving the adenovirus containing HSV1-tk (3. 4+/
      2.2-fold increase of radioactivity at vector administration site compared with
      remote myocardium), whereas nonspecific uptake in negative controls was low (<10%
      of positive controls). CONCLUSIONS: Using an adenoviral vector, HSV1-tk can be
      successfully expressed in cardiac cells in vitro and in vivo, yielding high
      uptake of radiolabeled FIAU. The results suggest that imaging transgene
      expression in the heart is feasible and may be used to monitor gene therapy
      noninvasively.

PMID- 10961957
TI  - Inhibition of restenosis with beta-emitting radiotherapy: Report of the
      Proliferation Reduction with Vascular Energy Trial (PREVENT).
AB  - BACKGROUND: Intracoronary gamma- and beta-radiation have reduced restenosis in
      animal models. In the clinical setting, the effectiveness of beta-emitters has
      not been studied in a broad spectrum of patients, particularly those receiving
      stents. METHODS AND RESULTS: A prospective, randomized, sham-controlled study of
      intracoronary radiotherapy with the beta-emitting (32)P source wire, using a
      centering catheter and automated source delivery unit, was conducted. A total of
      105 patients with de novo (70%) or restenotic (30%) lesions who were treated by
      stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24
      Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target
      site late loss index of 11+/-36% in radiotherapy patients versus 55+/-30% in
      controls (P:<0.0001). A low late loss index was seen in stented and balloon
      treated patients and was similar across the 16, 20, and 24 Gy radiotherapy
      groups. Restenosis (>/=50%) rates were significantly lower in radiotherapy
      patients at the target site (8% versus 39%; P:=0.012) and at target site plus
      adjacent segments (22% versus 50%; P:=0.018). Target lesion revascularization was
      needed in 5 radiotherapy patients (6%) and 6 controls (24%; P:<0.05). Stenosis
      adjacent to the target site and late thrombotic events reduced the overall
      clinical benefit of radiotherapy. CONCLUSIONS: beta-radiotherapy with a centered
      (32)P source is safe and highly effective in inhibiting restenosis at the target
      site after stent or balloon angioplasty. However, minimizing edge narrowing and
      late thrombotic events must be accomplished to maximize the clinical benefit of
      this modality.

PMID- 10961958
TI  - Visualization of fibrous cap thickness and rupture in human atherosclerotic
      carotid plaque in vivo with high-resolution magnetic resonance imaging.
AB  - BACKGROUND: The results of studies of advanced lesions of atherosclerosis suggest
      that the thickness of the fibrous cap that overlies the necrotic core
      distinguishes the stable lesion from one that is at high risk for rupture and
      thromboembolic events. We have developed a high-resolution MRI technique that can
      identify the fine structure of the lesion, including the fibrous cap, in vivo.
      The aim of the present study was to determine the agreement between in vivo MRI
      and lesion architecture as seen on histology and gross tissue examination to
      identify fibrous cap thickness and rupture. METHODS AND RESULTS: Twenty-two
      subjects who were scheduled for carotid endarterectomy underwent MRI with a 3
      dimensional multiple overlapping thin slab angiography protocol. The appearance
      of the fibrous cap was categorized as (1) an intact, thick, (2) an intact, thin,
      or (3) a ruptured fibrous cap on MRI, gross, and histological sections. Thirty
      six sites were available for comparison between MRI and histology. There was a
      high level of agreement between MRI and histological findings: 89% agreement,
      kappa (95% CI)=0.83 (0.67 to 1. 0), weighted kappa=0.87. Spearman's correlation
      coefficient was 0.88 (significant to the 0.01 level). CONCLUSIONS: These findings
      indicate that high-resolution MRI with a 3-dimensional multiple overlapping thin
      slab angiography protocol is capable of distinguishing intact, thick fibrous caps
      from intact thin and disrupted caps in atherosclerotic human carotid arteries in
      vivo. This noninvasive technique has the potential to permit studies that examine
      the relationship between fibrous cap changes and clinical outcome and to permit
      trials that evaluate therapy intended to "stabilize" the fibrous cap.

PMID- 10961959
TI  - Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene
      transfer for therapeutic angiogenesis in chronic myocardial ischemia.
AB  - BACKGROUND: NOGA left ventricular (LV) electromechanical mapping (EMM) can be
      used to distinguish among infarcted, ischemic, and normal myocardium. We
      investigated the use of percutaneous LV EMM to assess the efficacy of myocardial
      gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth
      factor (phVEGF(165)), administered during surgery by direct myocardial injection
      in patients with chronic myocardial ischemia. METHODS AND RESULTS: A total of 13
      consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable
      angina due to angiographically documented coronary artery disease, all of whom
      had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with
      direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of
      ischemic myocardium were identified on LV EMM by preserved viability associated
      with an impairment in linear local shortening. Myocardial viability, defined by
      mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did
      not change significantly after GTx. Analysis of linear local shortening in areas
      of myocardial ischemia, however, disclosed significant improvement after (15.26+/
      0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of
      ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to
      0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved
      perfusion scores calculated from single-photon emission CT-sestamibi myocardial
      perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after
      GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus
      8.5+/-1.7 after GTx, P:=0.047). CONCLUSIONS: The results of EMM constitute
      objective evidence that phVEGF(165) GTx augments perfusion of ischemic
      myocardium. These findings, together with reduction in the size of the defects
      documented at rest by serial single-photon emission CT-sestamibi imaging, suggest
      that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.

PMID- 10961960
TI  - Physical activity and coronary heart disease in men: The Harvard Alumni Health
      Study.
AB  - BACKGROUND: The quantity and intensity of physical activity required for the
      primary prevention of coronary heart disease (CHD) remain unclear. Therefore, we
      examined the association of the quantity and intensity of physical activity with
      CHD risk and the impact of other coronary risk factors. METHODS AND RESULTS: We
      followed 12 516 middle-aged and older men (mean age 57.7 years, range 39 to 88
      years) from 1977 through 1993. Physical activity was assessed at baseline in
      kilojoules per week (4.2 kJ=1 kcal) from blocks walked, flights climbed, and
      participation in sports or recreational activities. During follow-up, 2,135 cases
      of incident CHD, including myocardial infarction, angina pectoris,
      revascularization, and coronary death, occurred. Compared with men expending
      <2,100 kJ/wk, men expending 2,100 to 4,199, 4,200 to 8,399, 8,400 to 12,599, and
      >/=12,600 kJ/wk had multivariate relative risks of 0.90, 0.81, 0.80, and 0.81,
      respectively (P: for trend=0.003). When we considered the independent effects of
      specific physical activity components, only total sports or recreational
      activities (P: for trend=0.042) and vigorous activities (P: for trend=0.02) were
      inversely associated with the risk of CHD. These associations did not differ
      within subgroups of men defined by coronary risk factors. Finally, among men with
      multiple coronary risk factors, those expending >/=4,200 kJ/wk had reduced CHD
      risk compared with men expending <4,200 kJ/wk. CONCLUSIONS: Total physical
      activity and vigorous activities showed the strongest reductions in CHD risk.
      Moderate and light activities, which may be less precisely measured, showed
      nonsignificant inverse associations. The association between physical activity
      and a reduced risk of CHD also extends to men with multiple coronary risk
      factors.

PMID- 10961961
TI  - Physical activity and coronary heart disease risk in men: does the duration of
      exercise episodes predict risk?
AB  - BACKGROUND: Physical activity is associated with a decreased risk of coronary
      heart disease (CHD). However, it is unclear whether the duration of exercise
      episodes is important: Are accumulated shorter sessions as predictive of
      decreased risk as longer sessions if the same amount of energy is expended?
      METHODS AND RESULTS: In the Harvard Alumni Health Study, we prospectively
      followed 7307 Harvard University alumni (mean age 66.1 years) from 1988 through
      1993. At baseline, men reported their walking, stair climbing, and participation
      in sports or recreational activities. For each of the latter activities, they
      also reported the frequency and average duration per episode. During follow-up,
      482 men developed CHD. In age-adjusted analysis, a longer duration of exercise
      episodes predicted lower CHD risk (P: trend=0.04). However, after total energy
      expended on physical activity and potential confounders was accounted for,
      duration no longer had an independent effect on CHD risk (P: trend=0.25); that
      is, longer sessions of exercise did not have a different effect on risk compared
      with shorter sessions, as long as the total energy expended was similar. In
      contrast, higher levels of total energy expenditure significantly predicted
      decreased CHD risk in both age-adjusted (P: trend=0.009) and multivariate (P:
      trend=0.046) analyses. CONCLUSIONS: These data clearly indicate that physical
      activity is associated with decreased CHD risk. Furthermore, they lend some
      support to recent recommendations that allow for the accumulation of shorter
      sessions of physical activity, as opposed to requiring 1 longer, continuous
      session of exercise. This may provide some impetus for those sedentary to become
      more active.

PMID- 10961962
TI  - Postexercise ischemia is associated with increased neuropeptide Y in patients
      with coronary artery disease.
AB  - BACKGROUND: Neurohormones may influence vascular tone both during and after
      exercise. Neuropeptide Y (NPY), which is costored and released with
      norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with
      a relatively long half-life. We therefore examined its possible association with
      the ischemic response to exercise in patients with coronary artery disease.
      METHODS AND RESULTS: Twenty-nine male patients with effort-induced angina
      pectoris underwent a symptom-limited exercise test. In addition to conventional
      ST-segment analysis, we examined ischemia on the basis of heart rate (HR)
      adjusted ST-segment changes through calculation of the ST/HR slope during the
      final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood
      samples were taken before, during, and after exercise for an analysis of several
      neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just
      before the termination of exercise, followed by a gradual normalization, but it
      remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end
      of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77
      microV/HR. In most patients, ST-segment levels at a given HR were lower during
      recovery than during exercise, here referred to as ST "deficit." Exercise
      increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial
      natriuretic peptide, but big endothelin remained unchanged. Although NE and
      epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal
      proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal
      increase in the NPY correlated significantly with ST-segment depression at 3
      minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding
      time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after
      exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE.
      CONCLUSIONS: The present study has for the first time demonstrated a correlation
      between plasma NPY levels and the degree and duration of ST-segment depression
      after exercise in patients with coronary artery disease, which suggests that NPY
      may contribute to myocardial ischemia in these patients.

PMID- 10961963
TI  - Acute systemic inflammation impairs endothelium-dependent dilatation in humans.
AB  - BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the
      association between an acute inflammatory episode and the transiently increased
      risk of a cardiovascular event by examining the effects of an experimental
      inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS:
      Salmonella typhi vaccine was used to generate a systemic inflammatory response in
      healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and
      to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in
      6 subjects, venous occlusion plethysmography was used to measure forearm blood
      flow during intrabrachial infusion of the endothelium-dependent dilators
      acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators
      NTG and verapamil (resistance vessel response). Responses were assessed 16 hours
      before and 8 and 32 hours after vaccination. Vaccination resulted in elevations
      in white cell count and serum levels of interleukin-6 and interleukin-1 receptor
      antagonist. Eight hours after vaccination, resistance vessel responses to BK
      (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery
      flow-mediated dilatation was depressed. Resistance vessel responses to verapamil
      and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two
      hours after vaccination, resistance vessel responses to BK and ACh had returned
      to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction
      associated with temporary but profound dysfunction of the arterial endothelium in
      both resistance and conduit vessels to both physical and pharmacological dilator
      stimuli. This finding might explain the association between infection and
      inflammation and the enhanced risk of an acute cardiovascular event.

PMID- 10961964
TI  - Elevated C-reactive protein levels and impaired endothelial vasoreactivity in
      patients with coronary artery disease.
AB  - BACKGROUND: Elevated C-reactive protein (CRP) serum levels, an exquisitely
      sensitive objective marker of inflammation, relate to long-term prognosis in
      patients with coronary artery disease and in apparently healthy men. Because
      abnormalities of endothelial regulation of vascular function may contribute to
      the occurrence of coronary events, we tested the hypothesis that elevated CRP
      levels are associated with an abnormal systemic endothelial vascular reactivity.
      METHODS AND RESULTS: Endothelium-dependent (10 to 50 microg/min acetylcholine)
      and endothelium-independent (2 to 8 microg/min sodium nitroprusside) forearm
      blood flow responses were measured with venous occlusion plethysmography in 60
      male patients with angiographically documented coronary artery disease. Forearm
      blood flow responses to acetylcholine were inversely correlated with CRP serum
      levels (r=-0.46, P:=0.001). With multivariate analysis that included the classic
      risk factors for coronary artery disease, elevated CRP serum level remained a
      statistically significant independent predictor of a blunted endothelial
      vasodilator capacity. Most important, normalization of elevated CRP levels over
      time was associated with a normalization of endothelium-mediated forearm blood
      flow responses after 3 months. CONCLUSIONS: Thus, elevated CRP serum levels
      indicative of a systemic inflammatory response are associated with a blunted
      systemic endothelial vasodilator function. The identification of elevated CRP
      levels as a transient independent risk factor for endothelial dysfunction might
      provide an important clue to link a systemic marker of inflammation to
      atherosclerotic disease progression.

PMID- 10961965
TI  - Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe
      unstable angina.
AB  - BACKGROUND: Unstable angina is associated with enhanced lipid peroxidation and
      reduced antioxidant defenses. We have previously reported aspirin failure in the
      suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of
      platelet activation in this setting. We tested the hypothesis that the in vivo
      formation of the F(2)-isoprostane 8-iso-prostaglandin (PG)F(2alpha), a bioactive
      product of arachidonic acid peroxidation, is enhanced in unstable angina and
      contributes to aspirin-insensitive TX biosynthesis. METHODS AND RESULTS: Urine
      samples were obtained from patients with unstable angina (n=32), stable angina
      (n=32), or variant angina (n=4) and from 40 healthy subjects for the measurement
      of immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2). 8-Iso-PGF(2alpha)
      excretion was significantly higher in patients with unstable angina (339+/-122
      pg/mg creatinine) than in matched patients with stable angina (236+/-83 pg/mg
      creatinine, P:=0.001) and control subjects (192+/-71 pg/mg creatinine,
      P:<0.0001). In patients with unstable angina, 8-iso-PGF(2alpha) was linearly
      correlated with 11-dehydro-TXB(2) excretion (rho=0.721, P:<0.0001) and inversely
      correlated with plasma vitamin E (rho=-0.710, P:=0. 004). Spontaneous myocardial
      ischemia in patients with variant angina or ischemia elicited by a stress test in
      patients with stable angina was not accompanied by any change in 8-iso
      PGF(2alpha) excretion, thus excluding a role of ischemia per se in the induction
      of increased F(2)-isoprostane production. CONCLUSIONS: These findings establish a
      putative biochemical link between increased oxidant stress and aspirin
      insensitive TX biosynthesis in patients with unstable angina and provide a
      rationale for dose-finding studies of antioxidants in this setting.

PMID- 10961966
TI  - Impact of diabetes on long-term prognosis in patients with unstable angina and
      non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess
      Strategies for Ischemic Syndromes) Registry.
AB  - BACKGROUND: Although unstable coronary artery disease is the most common reason
      for admission to a coronary care unit, the long-term prognosis of patients with
      this diagnosis is unknown. This is particularly true for patients with diabetes
      mellitus, who are known to have a high morbidity and mortality after an acute
      myocardial infarction. METHODS AND RESULTS: Prospectively collected data from 6
      different countries in the Organization to Assess Strategies for Ischemic
      Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of
      diabetic and nondiabetic patients who were hospitalized with unstable angina or
      non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%)
      had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than
      nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of
      catheterization and angioplasty. Diabetes independently predicted mortality
      (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as
      cardiovascular death, new myocardial infarction, stroke, and new congestive heart
      failure. Moreover, compared with their nondiabetic counterparts, women had a
      significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28;
      95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without
      prior cardiovascular disease had the same event rates for all outcomes as
      nondiabetic patients with previous vascular disease. CONCLUSIONS: Hospitalization
      for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year
      morbidity and mortality; this is especially evident for patients with diabetes.
      Diabetic patients with no previous cardiovascular disease have the same long-term
      morbidity and mortality as nondiabetic patients with established cardiovascular
      disease after hospitalization for unstable coronary artery disease.

PMID- 10961967
TI  - Red wine intake prevents nuclear factor-kappaB activation in peripheral blood
      mononuclear cells of healthy volunteers during postprandial lipemia.
AB  - BACKGROUND: Several epidemiological studies have demonstrated the beneficial
      effect of red wine intake in reducing total and cardiovascular mortality. This
      effect has been attributed in part to its antioxidant properties. Because the
      monocytes/macrophages and the nuclear transcription factor kappaB (NF-kappaB) are
      implicated in the pathogenesis of atherosclerotic lesions, we examined the effect
      of red wine intake on the activation of NF-kappaB in peripheral blood mononuclear
      cells. METHODS AND RESULTS: Sixteen healthy volunteers were studied 3 times each:
      after a moderate dose, a low dose, and no wine with a fat-enriched breakfast.
      Lipid profile and NF-kappaB activation (electrophoretic mobility shift assay)
      were examined in blood samples taken before and 3, 6, and 9 hours after wine
      intake. In addition, mononuclear cells were incubated with VLDL in the presence
      of some antioxidants (quercetin and alpha-tocopherol succinate) contained in red
      wine to study their effects on NF-kappaB activation. Subjects receiving a fat
      enriched breakfast had increased NF-kappaB activation in peripheral blood
      mononuclear cells coinciding with the augmentation in total triglycerides and
      chylomicrons. Red wine intake prevented NF-kappaB activity even though it induced
      a certain increase in serum lipids, particularly VLDL, that did not increase
      after the fat ingestion alone. However, another form of alcohol intake (vodka)
      did not modify the NF-kappaB activation provided by postprandial lipemia. In
      cultured mononuclear cells, isolated human VLDL caused NF-kappaB activation in a
      time-dependent manner that did not occur in the presence of the red wine
      antioxidants quercetin and alpha-tocopherol. CONCLUSIONS: Our results provide a
      new potential mechanism to explain the beneficial effects of red wine intake in
      the reduction of cardiovascular mortality.

PMID- 10961968
TI  - Biventricular pacing decreases sympathetic activity compared with right
      ventricular pacing in patients with depressed ejection fraction.
AB  - BACKGROUND: Although there have been few studies in which the hemodynamic effects
      of right ventricular (RV) and left ventricular (LV) pacing were compared with
      those of biventricular (BV) pacing, the autonomic changes during these different
      pacing modes remain unknown. We hypothesized that BV pacing results in improved
      hemodynamics and a decrease in sympathetic nerve activity (SNA) compared with
      single-site pacing. METHODS AND RESULTS: Thirteen men with a mean ejection
      fraction of 0.28+/-0.7 were enrolled in the study. Arterial blood pressure (BP),
      central venous pressure (CVP), and SNA were recorded during 3 minutes of right
      atrial (RA)-RV, RA-LV, and RA-BV pacing at a rate 10 beats faster than sinus
      rhythm. BP was greater during LV (151+/-7/85+/-3 mm Hg) and BV (151+/-6/85+/-3 mm
      Hg) pacing than during RV pacing (146+/-7/82+/-3 mm Hg) (P:<0.05). There were no
      differences in CVP among all pacing modes (P:=0.27). SNA was significantly less
      (P:<0.02) during both LV (606+/-35 U) and BV (582+/-41 U) pacing compared with RV
      pacing (685+/-32 U) (P:<0.02). Although not statistically significant (P:=0. 08
      to 0.14), there was a trend for patients with a narrow QRS to have a lower mean
      BP and higher SNA during LV pacing than during BV pacing (r=0.42 to 0.49).
      CONCLUSIONS: LV-based pacing results in improved hemodynamics and a decrease in
      SNA compared with RV pacing in patients with LV dysfunction regardless of the QRS
      duration.

PMID- 10961969
TI  - Effect of chronic treatment with the inducible nitric oxide synthase inhibitor N
      iminoethyl-L-lysine or with L-arginine on progression of coronary and aortic
      atherosclerosis in hypercholesterolemic rabbits.
AB  - BACKGROUND: We examined the implications of iNOS in atherosclerosis progression
      using the selective inducible NO synthase (iNOS) inhibitor N:-iminoethyl-L-lysine
      (L-NIL) in hypercholesterolemic rabbits. METHODS AND RESULTS: Nine rabbits were
      fed a 0.3% cholesterol diet for 24 weeks (Baseline group); 25 animals were
      maintained on the diet and treated for 12 extra weeks with L-NIL (5 mg x kg(-1) x
      d(-1), L-NIL group, n=8), vehicle (Saline group, n=9), or L-arginine (2.25%, L
      Arg group, n=8). In abdominal aortas of Saline rabbits, the lesions (53.7+/-5.7%,
      Baseline) increased to 75.0+/-5.0% (P:<0.05) but remained unaltered in the L-NIL
      group (63. 4+/-6.6%). Similar results were obtained for the intima/media ratio in
      thoracic aortas. In coronary arteries, the intima/media ratio was comparable in
      Baseline (0.68+/-0.18) and Saline (0.96+/-0.19) rabbits but decreased to 0.34+/
      0.19 (P:<0.05) in L-NIL rabbits. L-Arginine had beneficial effects only in
      abdominal aortas. An increased thoracic aorta collagen content was found in
      Saline and L-Arg but not in L-NIL rabbits. In thoracic aortas of the Saline
      group, acetylcholine caused modest relaxations that slightly increased by L
      arginine but not by L-NIL. Relaxations to nitroglycerin were ameliorated by L
      NIL. CONCLUSIONS: This is the first study showing that chronic treatment with an
      iNOS inhibitor, L-NIL, limits progression of preexisting atherosclerosis in
      hypercholesterolemic rabbits. Increased intimal collagen accumulation may
      participate in iNOS-induced atherosclerosis progression.

PMID- 10961970
TI  - Endothelial dysfunction after repeated Chlamydia pneumoniae infection in
      apolipoprotein E-knockout mice.
AB  - BACKGROUND: Arterial relaxation is largely regulated by endothelial nitric oxide
      (NO). Its diminished activity has been associated with incipient atherosclerosis.
      We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E
      knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae
      inoculation. METHODS AND RESULTS: Forty-eight apoE-KO mice, 8 weeks old, were
      inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks
      over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2
      weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle
      tone of aortic rings was measured in vitro at both time points. The
      norepinephrine-precontracted thoracic aortic rings were successively exposed to
      methacholine in the absence and presence of N:(G)-nitro-L-arginine methyl ester
      (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in
      the infected mice at 6 weeks in both the absence and presence of L-NAME (P:<0.05
      and P:<0.01, respectively). When administered together with L-NAME, diclofenac
      enhanced the relaxation of the L-NAME-pretreated aortas in infected mice at 2
      weeks (P:<0.05) but not in noninfected mice. The relaxation response from
      infected mice tended to differ in the same manner at 6 weeks (P:<0.1). No intimal
      thickening was detected at either time point. CONCLUSIONS: C pneumoniae impairs
      arterial endothelial function, and the NO pathway is principally involved.
      Cyclooxygenase-dependent vasoconstricting products may also account for the
      infection-induced impaired relaxation. These findings further support the role of
      C pneumoniae infection in atherosclerosis development.

PMID- 10961971
TI  - Microtubule depolymerization normalizes in vivo myocardial contractile function
      in dogs with pressure-overload left ventricular hypertrophy.
AB  - BACKGROUND: Because initially compensatory myocardial hypertrophy in response to
      pressure overloading may eventually decompensate to myocardial failure,
      mechanisms responsible for this transition have long been sought. One such
      mechanism established in vitro is densification of the cellular microtubule
      network, which imposes a viscous load that inhibits cardiocyte contraction.
      METHODS AND RESULTS: In the present study, we extended this in vitro finding to
      the in vivo level and tested the hypothesis that this cytoskeletal abnormality is
      important in the in vivo contractile dysfunction that occurs in experimental
      aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the
      ascending aorta had caused severe left ventricular (LV) pressure overloading
      (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured
      at baseline and 1 hour after the intravenous administration of colchicine.
      Cardiocytes obtained by biopsy before and after in vivo colchicine administration
      were examined in tandem. Microtubule depolymerization restored LV contractile
      function both in vivo and in vitro. CONCLUSIONS: These and additional
      corroborative data show that increased cardiocyte microtubule network density is
      an important mechanism for the ventricular contractile dysfunction that develops
      in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

PMID- 10961972
TI  - The power-velocity integral at the vena contracta: A new method for direct
      quantification of regurgitant volume flow.
AB  - BACKGROUND: Noninvasive quantification of regurgitation is limited because
      Doppler measures velocity, not flow. Because backscattered Doppler power is
      proportional to sonified blood volume, power times velocity should be
      proportional to flow rate. Early studies, however, suggested that this held only
      for laminar flow, not for regurgitant jets, in which turbulence and fluid
      entrainment augment scatter. We therefore hypothesized that this Doppler power
      principle can be applied at the proximal vena contracta, where flow is laminar
      before entrainment, so that the power-times-velocity integral should vary
      linearly with flow rate and its time integral with stroke volume (SV). METHODS
      AND RESULTS: This was tested in vitro with steady and pulsatile flow through 0.07
      to 0.8-cm(2) orifices and in 36 hemodynamic stages in vivo, replacing the left
      atrium with a rigid chamber and column for direct visual recording of mitral
      regurgitant SV (MRSV). In 12 patients, MRSV was compared with MRI mitral inflow
      minus aortic outflow and in 11 patients with 3D echo left ventricular ejection
      volume-Doppler aortic forward SV. Vena contracta power in the narrow high
      velocity spectrum from a broad measuring beam was calibrated against that from a
      narrow reference beam of known area. Calculated and actual flow rates and SV
      correlated well in vitro (r=0.99, 0.99; error=-1.6+/-2.5 mL/s, -2. 4+/-2.9 mL),
      in vivo (MRSV: r=0.98, error=0.04+/-0.87 mL), and in patients (MRSV: r=0.98,
      error=-2.8+/-4.5 mL). CONCLUSIONS: The power-velocity integral at the vena
      contracta provides an accurate direct measurement of regurgitant flow, overcoming
      the limitations of existing Doppler techniques.

PMID- 10961973
TI  - Lewis A. Conner: Cornell's Osler.
AB  - Lewis A. Conner, MD (1867 to 1950), was a pioneer in public health cardiology,
      cardiac rehabilitation, and cardiac psychology. He helped establish the Burke
      Rehabilitation Hospital and was the founding president of the New York and
      American Heart Associations (AHA). Dr Conner was the founder of the American
      Heart Journal, America's first medical subspecialty journal, and the official
      publication of the American Heart Association until 1950, when CIRCULATION: was
      created. Conner spent more than a half-century on the staff of the New York
      Hospital and Cornell University Medical College and was Chairman of Medicine from
      1916 to 1932. During this time, he created the innovative Cornell Pay Clinic and
      united the "old" New York Hospital with the new and scientifically-oriented
      Cornell University Medical College on a modern and inspiring urban campus. An
      extraordinary clinician and a humanist with great equanimity, Conner devoted his
      career to the Oslerian tradition of scholarship, leadership, and organization in
      the quest for improved patient care. This article contains newly discovered
      biographic material on Dr Conner and explores his professional and personal
      connection to Sir William Osler.

PMID- 10961974
TI  - Penetrating stab injury of the thoracic aorta.

PMID- 10961975
TI  - Core components of cardiac rehabilitation/secondary prevention programs: A
      statement for healthcare professionals from the American Heart Association and
      the American Association of Cardiovascular and Pulmonary Rehabilitation Writing
      Group.

PMID- 10961977
TI  - Meeting highlights : highlights of the 49th scientific sessions of the american
      college of cardiology

PMID- 10961976
TI  - Images in cardiovascular Medicine. Wide-complex tachycardia.

PMID- 10961978
TI  - Ranking of surgical performance.

PMID- 10961979
TI  - C-reactive protein as a clinical marker of risk.

PMID- 10961980
TI  - Use of targeted anticytokine treatments in heart failure.

PMID- 10961981
TI  - Collagen and transforming growth factor-beta in dilated cardiomyopathy.

PMID- 10961982
TI  - Paying for clinical trials.

PMID- 10961983
TI  - Vascular endothelial growth factor activates STAT proteins in aortic endothelial
      cells.
AB  - Vascular endothelial growth factor (VEGF) intracellular signaling in endothelial
      cells is initiated by the activation of distinct tyrosine kinase receptors,
      VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR). Because the tyrosine kinase-dependent
      transcription factors known as STAT (signal transducers and activators of
      transcription) proteins are important modulators of cell growth responses induced
      by other growth factor receptors, we have determined the effects VEGF of on STAT
      activation in BAEC (bovine aortic endothelial cells). Here, we show that VEGF
      induces tyrosine phosphorylation and nuclear translocation of STAT1 and STAT6.
      VEGF also stimulates STAT3 tyrosine phosphorylation, but nuclear translocation
      does not occur. We found that placenta growth factor, which selectively activates
      VEGFR1, has no effect on the STATs. However, upon VEGF stimulation, STAT1
      associates with the VEGFR2 in a tyrosine kinase-dependent manner, indicating that
      VEGF-induced STAT1 activation is mediated primarily by VEGFR2. Thus, our study
      shows for the first time that VEGF activates the STAT pathway through VEGFR2.
      Because the growth-promoting activity of VEGF depends upon VEGFR2 activation,
      these findings suggest a role for the STATs in the regulation of gene expression
      associated with the angiogenic effects of VEGF.

PMID- 10961984
TI  - Distinct pathways for stimulation of cytochrome c release by etoposide.
AB  - Induction of apoptosis by DNA-damaging agents, such as etoposide, is known to
      involve the release of mitochondrial cytochrome c, although the mechanism
      responsible for this event is unclear. In the present study, using Jurkat T
      lymphocytes, a reconstituted cell-free system, or isolated liver mitochondria, we
      demonstrate the ability of etoposide to induce cytochrome c release via two
      distinct pathways. Caspase inhibition by either benzyloxycarbonyl-Val-Ala-Asp
      fluoromethyl ketone (z-VAD-fmk) or benzyloxycarbonyl-Val-Asp-Val-Ala-Asp
      fluoromethyl ketone (z-VDVAD-fmk) attenuates cytochrome c release triggered by a
      low dose of etoposide via an apparent inhibition of nuclear events involving the
      release of protein factor(s) that is (are) able to interact with mitochondria. In
      contrast, caspase inhibition has no effect on cytochrome c release induced by a
      higher dose of etoposide. Moreover, the higher dose of etoposide heightens the
      sensitivity of Ca(2+)-loaded isolated mitochondria to mitochondrial permeability
      transition, an effect that is completely abolished by cyclosporin A.
      Interestingly, cyclosporin A is ineffective at preventing similar mitochondrial
      damage in Jurkat cells treated with etoposide. We propose that lower doses of
      etoposide predominantly target the nucleus and stimulate the release of caspase
      sensitive protein factor(s) that interact with mitochondria to trigger cytochrome
      c release, whereas higher doses of the drug impart a more direct effect on
      mitochondria and thus are not mitigated by caspase inhibition.

PMID- 10961985
TI  - Identification of two novel zinc finger modules and nuclear localization signal
      in rat spermatidal protein TP2 by site-directed mutagenesis.
AB  - Spermatidal protein TP2, which appears transiently during stages 12-16 of
      mammalian spermiogenesis, is a DNA condensing zinc metalloprotein with a
      preference to GC-rich DNA. We have carried out a detailed site-directed
      mutagenesis analysis of rat spermatidal protein TP2 to delineate the amino acid
      residues involved in coordination with two atoms of zinc. Two zinc fingers
      modules have been identified involving 4 histidine and 4 cysteine residues,
      respectively. The modular structure of the two zinc fingers identified in TP2
      define a new class of zinc finger proteins that do not fall into any of the known
      classes of zinc fingers. Transfection experiments with COS-7 cells using wild
      type and the two zinc finger pocket mutants have shown that TP2 preferentially
      localizes to nucleolus. The nuclear localization signal in TP2 was identified to
      be (87)GKVSKRKAV(95) present in the C-terminal third of TP2 as a part of an
      extended NoLS sequence.

PMID- 10961986
TI  - Large isoform of hepatitis delta antigen activates serum response factor
      associated transcription.
AB  - Hepatitis delta virus infection sometimes causes severe and fulminant hepatitis
      as a coinfection or superinfection along with the hepatitis B virus. To elucidate
      the underlying mechanism of injury caused by hepatitis delta virus, we examined
      whether two isoforms of the hepatitis delta antigen (HDAg) had any effect on five
      well defined intracellular signal transduction pathways: serum response factor
      (SRF)-, serum response element (SRE)-, nuclear factor kappaB-, activator protein
      1-, and cyclic AMP response element-dependent pathways. Reporter assays revealed
      that large HDAg (LHDAg) activated the SRF- and SRE-dependent pathways. In
      contrast, small HDAg (SHDAg) did not activate any of five pathways. LHDAg
      enhanced the transcriptional ability of SRF without changing its DNA binding
      affinity in an electrophoretic mobility shift assay. In addition, LHDAg activated
      a rat SM22alpha promoter containing SRF binding site and a human c-fos promoter
      containing SRE. In conclusion, LHDAg, but not SHDAg, enhances SRF-associated
      transcriptions. Despite structural similarities between the two HDAgs, there are
      significant differences in their effects on intracellular signal transduction
      pathways. These results may provide clues that will aid in the clarification of
      functional differences between LHDAg and SHDAg and the pathogenesis of delta
      hepatitis.

PMID- 10961987
TI  - Phosphorylation of the beta-galactoside-binding protein galectin-3 modulates
      binding to its ligands.
AB  - The beta-galactoside-binding protein galectin-3 has pleiotropic biological
      functions and has been implicated in cell growth, differentiation, adhesion, RNA
      processing, apoptosis, and malignant transformation. Galectin-3 may be
      phosphorylated at N-terminal Ser(6), but the role of phosphorylation in
      determining interactions of this endogenous lectin with its ligands remains to be
      elucidated. We therefore studied the effect of phosphorylation on binding of
      galectin-3 to two of its reported ligands, laminin and purified colon cancer
      mucin. Human recombinant galectin-3 was phosphorylated in vitro by casein kinase
      I, and separated from the native species by isoelectric focusing for use in solid
      phase binding assays. Non-phosphorylated galectin-3 bound to laminin and
      asialomucin in a dose-dependent manner with half-maximal binding at 1.5
      microg/ml. Phosphorylation reduced saturation binding to each ligand by >85%.
      Ligand binding could be fully restored by dephosphorylation with protein
      phosphatase type 1. Mutation of galectin-3 at Ser(6) (Ser to Glu) did not alter
      galectin ligand binding. Metabolic labeling or separation by isoelectric focusing
      confirmed the presence of phosphorylated galectin-3 species in vivo in the
      cytosol of human colon cancer cells from which ligand mucin was purified.
      Phosphorylation significantly reduces the interaction of galectin-3 with its
      ligands. The process by which phosphorylation modulates protein-carbohydrate
      interactions has important implications for understanding the biological
      functions of this protein, and may serve as an "on/off" switch for its sugar
      binding capabilities.

PMID- 10961988
TI  - Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular
      mechanism and functional consequences.
AB  - We used whole cell recording to evaluate functional expression of the
      intermediate conductance Ca(2+)-activated K(+) channel, IKCa1, in response to
      various mitogenic stimuli. One to two days following engagement of T-cell
      receptors to trigger both PKC- and Ca(2+)-dependent events, IKCa1 expression
      increased from an average of 8 to 300-800 channels/cell. Selective stimulation of
      the PKC pathway resulted in equivalent up-regulation, whereas a calcium ionophore
      was relatively ineffective. Enhancement in IKCa1 mRNA levels paralleled the
      increased channel number. The genomic organization of IKCa1, SKCa2, and SKCa3
      were defined, and IK(Ca) and SK(Ca) genes were found to have a remarkably similar
      intron-exon structure. Mitogens enhanced IKCa1 promoter activity proportional to
      the increase in IKCa1 mRNA, suggesting that transcriptional mechanisms underlie
      channel up-regulation. Mutation of motifs for AP1 and Ikaros-2 in the promoter
      abolished this induction. Selective Kv1.3 inhibitors ShK-Dap(22), margatoxin, and
      correolide suppressed mitogenesis of resting T-cells but not preactivated T-cells
      with up-regulated IKCa1 channel expression. Selectively blocking IKCa1 channels
      with clotrimazole or TRAM-34 suppressed mitogenesis of preactivated lymphocytes,
      whereas resting T-cells were less sensitive. Thus, Kv1.3 channels are essential
      for activation of quiescent cells, but signaling through the PKC pathway enhances
      expression of IKCa1 channels that are required for continued proliferation.

PMID- 10961989
TI  - Leucine 42 in the fibronectin motif of streptokinase plays a critical role in
      fibrin-independent plasminogen activation.
AB  - The NH(2) terminus (residues 1-59) of streptokinase (SK) is a molecular switch
      that permits fibrin-independent plasminogen activation. Targeted mutations were
      made in recombinant (r) SK1-59 to identify structural interactions required for
      this process. Mutagenesis established the functional roles of Phe-37and Glu-39,
      which were projected to interact with microplasmin in the activator complex.
      Mutation of Leu-42 (rSK1-59(L42A)), a conserved residue in the SK fibronectin
      motif that lacks interactions with microplasmin, strongly reduced plasminogen
      activation (k(cat) decreased 50-fold) but not amidolysis (k(cat) decreased 1.5
      fold). Otherwise rSK1-59(L42A) and native rSK1-59 were indistinguishable in
      several parameters. Both displayed saturable and specific binding to Glu
      plasminogen or the remaining SK fragment (rSKDelta59). Similarly rSK1-59 and rSK1
      59(L42A) bound simultaneously to two different plasminogen molecules, indicating
      that both plasminogen binding sites were intact. However, when bound to
      SKDelta59, rSK1-59(L42A) was less effective than rSK1-59 in restructuring the
      native conformation of the SK A domain, as detected by conformation-dependent
      monoclonal antibodies. In the light of previous studies, these data provide
      evidence that SK1-59 contributes to fibrin-independent plasminogen activation
      through 1) intermolecular interactions with the plasmin in the activator complex,
      2) binding interactions with the plasminogen substrate, and 3) intramolecular
      interactions that structure the A domain of SK for Pg substrate processing.

PMID- 10961990
TI  - Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role
      of hsp90.
AB  - The aryl hydrocarbon receptor (AhR) has been shown to interact with an
      immunophilin-like molecule known as AhR-interacting protein (AIP) and to enhance
      AhR function. We show here that AIP associates with AhR homologues from mouse and
      fish, which can bind ligands such as dioxin, but nonligand binding homologues
      from Caenorhabditis elegans or Drosophila do not bind to AIP. However, a minimal
      ligand-binding domain of the AhR is incapable of binding AIP. The binding of AIP
      to AhR in reticulocyte lysate shows several of the characteristics of an hsp90
      dependent process, including sensitivity to geldanamycin and temperature and a
      requirement for ATP or nonhydrolyzable analogues. Purified AIP binds to the C
      terminus of hsp90, and mutation of a conserved basic residue in the
      tetratricopeptide repeats of AIP (K266A, analogous to K97A in protein phosphatase
      5) abolishes binding to hsp90. Mutation of K266A in AIP reduces binding to AhR by
      75-80%; the geldanamycin sensitivity of this complex shows that AhR stabilizes
      the AIP-hsp90-AhR complex. The alpha-helical C terminus of AIP, which is outside
      the tetratricopeptide repeat domain, is absolutely required for binding to AhR as
      shown by deletions of the C-terminal 5 amino acids or alanine-scanning
      mutagenesis, but it is not required for binding of AIP to hsp90. The data support
      a model where 1) AIP binds to both hsp90 and AhR; 2) hsp90 is required for AhR
      AIP binding; and 3) the binding of AhR to AIP stabilizes the AIP-hsp90-AhR
      complex.

PMID- 10961991
TI  - Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73
      identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif.
AB  - Two-hybrid screening in yeast with p73alpha isolated SUMO-1 (small ubiquitin-like
      modifier 1), the enzyme responsible for its conjugation, Ubc-9, and a number of
      novel SUMO-1-interacting proteins, including thymine DNA glycosylase, PM-Scl75,
      PIASx, PKY, and CHD3/ZFH. A subset of these proteins contain a common motif,
      hhXSXS/Taaa, where h is a hydrophobic amino acid and a is an acidic amino acid,
      that is shown to interact with SUMO-1 in the two-hybrid system. We show here that
      p73alpha, but not p73beta, can be covalently modified by SUMO-1. The major SUMO-1
      modified residue in p73alpha is the C-terminal lysine (Lys(627)). The sequence
      surrounding this lysine conforms to a consensus SUMO-1 modification site
      b(X)XXhKXE, where b is a basic amino acid. SUMO-1-modified p73 is more rapidly
      degraded by the proteasome than unmodified p73, although SUMO-1 modification is
      not required for p73 degradation. SUMO-1 modification does not affect the
      transcriptional activity of p73alpha on an RGC-luciferase reporter gene in SK-N
      AS cells. Instead, SUMO-1 modification may alter the subcellular localization of
      p73, because SUMO-1-modified p73 is preferentially found in detergent-insoluble
      fractions. Alternatively, it may modulate the interaction of p73 with other
      proteins that are substrates for SUMO-1 modification or which interact with SUMO
      1, such as those identified here.

PMID- 10961992
TI  - Induction of the BRCA2 promoter by nuclear factor-kappa B.
AB  - BRCA2 is a tumor suppressor gene that has been implicated in response to DNA
      damage, cell cycle control, and transcription. BRCA2 has been found to be
      overexpressed in many breast tumors, suggesting that altered expression of the
      BRCA2 gene may contribute to breast tumorigenesis. To determine how BRCA2 is
      overexpressed in tumors, we investigated the transcriptional regulation of the
      BRCA2 promoter. Deletion mapping of the BRCA2 promoter identified three regions
      associated with 3-fold activation or repression and one upstream stimulatory
      factor binding site associated with 20-fold activation. Gel shift and
      cotransfection studies verified the role of USF in regulation of BRCA2
      transcription. Analysis of the -144 to -59 region associated with 3-fold
      activation identified a putative NFkappaB binding site. Cotransfection of the p65
      and p50 subunits of NFkappaB up-regulated the BRCA2 promoter 16-fold in a
      luciferase reporter assay, whereas mutations in the binding site ablated the
      effect. Gel shift and supershift assays with anti-p65 and -p50 antibodies
      demonstrated that NFkappaB binds specifically to the NFkappaB site. In addition,
      ectopic expression of NFkappaB resulted in increased levels of endogeneous BRCA2
      expression. Thus, NFkappaB and USF regulate BRCA2 expression through the BRCA2
      promoter.

PMID- 10961993
TI  - Structure of C42D Azotobacter vinelandii FdI. A Cys-X-X-Asp-X-X-Cys motif ligates
      an air-stable [4Fe-4S]2+/+ cluster.
AB  - All naturally occurring ferredoxins that have Cys-X-X-Asp-X-X-Cys motifs contain
      [4Fe-4S](2+/+) clusters that can be easily and reversibly converted to [3Fe
      4S](+/0) clusters. In contrast, ferredoxins with unmodified Cys-X-X-Cys-X-X-Cys
      motifs assemble [4Fe-4S](2+/+) clusters that cannot be easily interconverted with
      [3Fe-4S](+/0) clusters. In this study we changed the central cysteine of the
      Cys(39)-X-X-Cys(42)-X-X-Cys(45) of Azotobacter vinelandii FdI, which coordinates
      its [4Fe-4S](2+/+) cluster, into an aspartate. UV-visible, EPR, and CD
      spectroscopies, metal analysis, and x-ray crystallography show that, like native
      FdI, aerobically purified C42D FdI is a seven-iron protein retaining its [4Fe
      4S](2+/+) cluster with monodentate aspartate ligation to one iron. Unlike known
      clusters of this type the reduced [4Fe-4S](+) cluster of C42D FdI exhibits only
      an S = 1/2 EPR with no higher spin signals detected. The cluster shows only a
      minor change in reduction potential relative to the native protein. All attempts
      to convert the cluster to a 3Fe cluster using conventional methods of oxygen or
      ferricyanide oxidation or thiol exchange were not successful. The cluster
      conversion was ultimately accomplished using a new electrochemical method.
      Hydrophobic and electrostatic interaction and the lack of Gly residues adjacent
      to the Asp ligand explain the remarkable stability of this cluster.

PMID- 10961994
TI  - Transit of tRNA through the Escherichia coli ribosome. Cross-linking of the 3'
      end of tRNA to specific nucleotides of the 23 S ribosomal RNA at the A, P, and E
      sites.
AB  - When bound to Escherichia coli ribosomes and irradiated with near-UV light,
      various derivatives of yeast tRNA(Phe) containing 2-azidoadenosine at the 3'
      terminus form cross-links to 23 S rRNA and 50 S subunit proteins in a site
      dependent manner. A and P site-bound tRNAs, whose 3' termini reside in the
      peptidyl transferase center, label primarily nucleotides U2506 and U2585 and
      protein L27. In contrast, E site-bound tRNA labels nucleotide C2422 and protein
      L33. The cross-linking patterns confirm the topographical separation of the
      peptidyl transferase center from the E site domain. The relative amounts of label
      incorporated into the universally conserved residues U2506 and U2585 depend on
      the occupancy of the A and P sites by different tRNA ligands and indicates that
      these nucleotides play a pivotal role in peptide transfer. In particular, the 3'
      adenosine of the peptidyl-tRNA analogue, AcPhe-tRNA(Phe), remains in close
      contact with U2506 regardless of whether its anticodon is located in the A site
      or P site. Our findings, therefore, modify and extend the hybrid state model of
      tRNA-ribosome interaction. We show that the 3'-end of the deacylated tRNA that is
      formed after transpeptidation does not immediately progress to the E site but
      remains temporarily in the peptidyl transferase center. In addition, we
      demonstrate that the E site, defined by the labeling of nucleotide C2422 and
      protein L33, represents an intermediate state of binding that precedes the entry
      of deacylated tRNA into the F (final) site from which it dissociates into the
      cytoplasm.

PMID- 10961995
TI  - Identification of a phospholemman-like protein from shark rectal glands. Evidence
      for indirect regulation of Na,K-ATPase by protein kinase c via a novel member of
      the FXYDY family.
AB  - The Na,K-ATPase provides the driving force for many ion transport processes
      through control of Na(+) and K(+) concentration gradients across the plasma
      membranes of animal cells. It is composed of two subunits, alpha and beta. In
      many tissues, predominantly in kidney, it is associated with a small ancillary
      component, the gamma-subunit that plays a modulatory role. A novel 15-kDa
      protein, sharing considerable homology to the gamma-subunit and to phospholemman
      (PLM) was identified in purified Na,K-ATPase preparations from rectal glands of
      the shark Squalus acanthias, but was absent in pig kidney preparations. This PLM
      like protein from shark (PLMS) was found to be a substrate for both PKA and PKC.
      Antibodies to the Na, K-ATPase alpha-subunit coimmunoprecipitated PLMS. Purified
      PLMS also coimmunoprecipitated with the alpha-subunit of pig kidney Na, K-ATPase,
      indicating specific association with different alpha-isoforms. Finally, PLMS and
      the alpha-subunit were expressed in stoichiometric amounts in rectal gland
      membrane preparations. Incubation of membrane bound Na,K-ATPase with non
      solubilizing concentrations of C(12)E(8) resulted in functional dissociation of
      PLMS from Na,K-ATPase and increased the hydrolytic activity. The same effects
      were observed after PKC phosphorylation of Na,K-ATPase membrane preparations.
      Thus, PLMS may function as a modulator of shark Na,K-ATPase in a way resembling
      the phospholamban regulation of the Ca-ATPase.

PMID- 10961996
TI  - Complete sequence of the 24-mer hemocyanin of the tarantula Eurypelma
      californicum. Structure and intramolecular evolution of the subunits.
AB  - Hemocyanins are large oligomeric respiratory proteins found in many arthropods
      and molluscs. The hemocyanin of the tarantula Eurypelma californicum is a 24-mer
      protein complex with molecular mass of 1, 726,459 Da that consists of seven
      different polypeptides (a-g), each occupying a distinct position within the
      native molecule. Here we report the complete molecular structure of the E.
      californicum hemocyanin as deduced from the corresponding cDNAs. This represents
      the first complex arthropod hemocyanin to be completely sequenced. The different
      subunits display 52-66% amino acid sequence identity. Within the subunits, the
      central domain, which bears the active center with the copper-binding sites A and
      B, displays the highest degree of identity. Using a homology modeling approach,
      the putative three-dimensional structure of individual subunits was deduced and
      compared. Phylogenetic analyses suggest that differentiation of the individual
      subunits occurred 400-550 million years ago. The hemocyanin of the stemline
      Chelicerata was probably a hexamer built up of six distinct subunit types a, b/c,
      d, e, f, and g, whereas that of the early Arachnida was originally a 24-mer that
      emerged after the differentiation of subunits b and c.

PMID- 10961997
TI  - Omega -crystallin of the scallop lens. A dimeric aldehyde dehydrogenase class 1/2
      enzyme-crystallin.
AB  - While many of the diverse crystallins of the transparent lens of vertebrates are
      related or identical to metabolic enzymes, much less is known about the lens
      crystallins of invertebrates. Here we investigate the complex eye of scallops.
      Electron microscopic inspection revealed that the anterior, single layered
      corneal epithelium overlying the cellular lens contains a regular array of
      microvilli that we propose might contribute to its optical properties. The sole
      crystallin of the scallop eye lens was found to be homologous to Omega
      crystallin, a minor crystallin in cephalopods related to aldehyde dehydrogenase
      (ALDH) class 1/2. Scallop Omega-crystallin (officially designated ALDH1A9) is 55
      56% identical to its cephalopod homologues, while it is 67 and 64% identical to
      human ALDH 2 and 1, respectively, and 61% identical to retinaldehyde
      dehydrogenase/eta-crystallin of elephant shrews. Like other enzyme-crystallins,
      scallop Omega-crystallin appears to be present in low amounts in non-ocular
      tissues. Within the scallop eye, immunofluorescence tests indicated that Omega
      crystallin expression is confined to the lens and cornea. Although it has
      conserved the critical residues required for activity in other ALDHs and appears
      by homology modeling to have a structure very similar to human ALDH2, scallop
      Omega-crystallin was enzymatically inactive with diverse substrates and did not
      bind NAD or NADP. In contrast to mammalian ALDH1 and -2 and other cephalopod
      Omega-crystallins, which are tetrameric proteins, scallop Omega-crystallin is a
      dimeric protein. Thus, ALDH is the most diverse lens enzyme-crystallin identified
      so far, having been used as a lens crystallin in at least two classes of molluscs
      as well as elephant shrews.

PMID- 10961999
TI  - Alternate aggregation pathways of the Alzheimer beta-amyloid peptide. An in vitro
      model of preamyloid.
AB  - Deposition of amyloid-beta (Abeta) aggregates in the brain is a defining
      characteristic of Alzheimer's disease (AD). Fibrillar amyloid, found in the cores
      of senile plaques, is surrounded by dystrophic neurites. In contrast, the
      amorphous Abeta (also called preamyloid) in diffuse plaques is not associated
      with neurodegeneration. Depending on the conditions, Abeta will also form
      fibrillar or amorphous aggregates in vitro. In this present study, we sought to
      characterize the properties of the amorphous aggregate and determine whether we
      could establish an in vitro model for amorphous Abeta. CD data indicated that
      Abeta40 assembled to form either a beta-structured aggregate or an unfolded
      aggregate with the structured aggregate forming at high peptide concentrations
      and the unstructured aggregate forming at low Abeta40 levels. The critical
      concentration separating these two pathways was 10 microm. Fluorescence emission
      and polarization showed the structured aggregate was tightly packed containing
      peptides that were not accessible to water. Peptides in the unstructured
      aggregate were loosely packed, mobile, and accessible to water. When examined by
      electron microscopy, the structured aggregate appeared as protofibrillar
      structures and formed classic amyloid fibrils over a period of several weeks. The
      unstructured aggregate was not visible by electron microscopy and did not
      generate fibrils. These findings suggest that the unstructured aggregate shares
      many properties with the amorphous Abeta of AD and that conditions can be
      established to form amorphous Abeta in vitro. This would allow for investigations
      to better understand the relationship between fibrillar and amorphous Abeta and
      could have significant impact upon efforts to find therapies for AD.

PMID- 10961998
TI  - The role of mitochondria in the regulation of hypoxia-inducible factor 1
      expression during hypoxia.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that
      regulates transcriptional activation of several genes responsive to the lack of
      oxygen, including erythropoietin, vascular endothelial growth factor, glycolytic
      enzymes, and glucose transporters. Because the involvement of mitochondria in the
      regulation of HIF-1 has been postulated, we tested the effects of mitochondrial
      electron transport chain deficiency on HIF-1 protein expression and DNA binding
      in hypoxic cells. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) inhibits electron transport chain at the level of complex I. MPTP is first
      converted to a pharmacologically active metabolite 1-methyl-4-phenylpyridinum
      (MPP+). MPP+ effectively inhibited both complex I activity and hypoxic
      accumulation of HIF-1alpha protein in dopaminergic cell lines PC12 and CATH.a. In
      C57BL/6 mice, a single dose of MPTP (15 mg/kg, intraperitoneal) inhibited complex
      I activity and HIF-1alpha protein accumulation in the striatum in response to a
      subsequent hypoxic challenge (8% O(2), 4 h). In a genetic model system, 40%
      complex I-inhibited human-ape xenomitochondrial cybrids, hypoxic induction of HIF
      1alpha was severely reduced, and HIF-1 DNA binding was diminished. However,
      succinate, the mitochondrial complex II substrate, restored the hypoxic response
      in cybrid cells, suggesting that electron transport chain activity is required
      for activation of HIF-1. A partial complex I deficiency and a mild reduction in
      intact cell oxygen consumption effectively prevented hypoxic induction of HIF
      1alpha protein.

PMID- 10962000
TI  - Insulin-like growth factor-I extends in vitro replicative life span of skeletal
      muscle satellite cells by enhancing G1/S cell cycle progression via the
      activation of phosphatidylinositol 3'-kinase/Akt signaling pathway.
AB  - Interest is growing in methods to extend replicative life span of non
      immortalized stem cells. Using the insulin-like growth factor I (IGF-I)
      transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle
      development and maturation prior to isolation and during culture of satellite
      cells (the myogenic stem cells of mature skeletal muscle fibers) as a model
      system, we elucidated the underlying molecular mechanisms of IGF-I-mediated
      enhancement of proliferative potential of these cells. Satellite cells from IGF-I
      transgenic muscles achieved at least five additional population doublings above
      the maximum that was attained by wild type satellite cells. This IGF-I-induced
      increase in proliferative potential was mediated via activation of the
      phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated
      protein kinase activity, facilitating G(1)/S cell cycle progression via a down
      regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of
      p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the
      increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A
      protein abundance, thereby implicating an important role for p27(Kip1) in
      promoting satellite cell senescence. These observations provide a more complete
      dissection of molecular events by which increased local expression of a growth
      factor in mature skeletal muscle fibers extends replicative life span of primary
      stem cells than previously known.

PMID- 10962001
TI  - Molecular cloning and expression of cDNA encoding chicken UDP-N-acetyl-D
      glucosamine (GlcNAc): GlcNAcbeta 1-6(GlcNAcbeta 1-2)- manalpha 1-R[GlcNAc to
      man]beta 1,4N-acetylglucosaminyltransferase VI.
AB  - A cDNA that encodes UDP-N-acetyl-d-glucosamine (GlcNAc):GlcNAcbeta1-6(GlcNAcbeta1
      2)Manalpha1-R[GlcNA c to Man]beta1, 4N-acetylglucosaminyltransferase VI (GnT VI),
      which is responsible for the formation of pentaantennary asparagine-linked
      oligosaccharides (N-glycans), has been cloned from a hen oviduct cDNA library
      based on the partial amino acid sequences of the purified enzyme. The isolated
      cDNA clone contained an open reading frame encoding 464 amino acids, including
      all of the peptides that were sequenced. The deduced amino acid sequence predicts
      a type II transmembrane topology and contains two potential N-glycosylation
      sites. The primary structure was found to be significantly similar to human GnT
      IV-homologue, the gene for which was cloned from the deleted region in pancreatic
      cancer, and to human and bovine GnT IVs. Chicken GnT VI-transfected COS-1 cells
      showed a high GnT VI activity (26.8 pmol/h/mg protein), whereas nontransfected,
      mock-transfected, or human GnT IV-homologue-transfected COS-1 cells had no
      activity. Northern blot analysis using poly(A)(+) RNA from hen oviduct indicated
      that the size of GnT VI mRNA is 2.1 kilobases. Reverse transcription-polymerase
      chain reaction analysis showed that GnT VI mRNA was relatively highly expressed
      in oviduct, spleen, lung, and colon.

PMID- 10962002
TI  - Sodium salicylate induces the expression of the immunophilin FKBP51 and biglycan
      genes and inhibits p34cdc2 mRNA both in vitro and in vivo.
AB  - One of the mechanisms proposed to explain the anti-inflammatory activity of
      sodium salicylate (NaSal) is based, at least in part, on its ability to inhibit
      nuclear factor-kappaB activation and inhibition of nuclear factor-kappaB
      dependent gene expression. On the other hand, little is known about the ability
      of NaSal to activate gene expression. By differential display reverse
      transcription polymerase chain reaction, we identified several genes that are
      modulated upon treatment of mouse fibroblasts with NaSal. From the various cDNA
      fragments recovered from autoradiograms, we found that NaSal can increase the
      levels of mRNA for biglycan, the mouse homologue of the human eIF-3 p47 unit, and
      immunophilin FKBP51. NaSal-induced expression of these genes was time- and dose
      dependent. Moreover, FKBP51 gene expression was augmented in vivo, in mice
      treated orally or intraperitoneally with NaSal. We also found that treating cells
      with NaSal can inhibit the expression of the p34(cdc2) kinase. The impact this
      inhibition on cell cycle was evaluated by measuring the content of DNA during the
      cell cycle. Treatment of cells with NaSal led to a G(2)/M arrest. By
      investigating the signaling events that regulate the expression of these genes
      and their biological activities, we can contribute to the understanding of the
      mechanism of NaSal.

PMID- 10962003
TI  - The inositol polyphosphate 5-phosphatases and the apurinic/apyrimidinic base
      excision repair endonucleases share a common mechanism for catalysis.
AB  - Inositol polyphosphate 5-phosphatases (5-phosphatase) hydrolyze the 5-position
      phosphate from the inositol ring of phosphatidylinositol-derived signaling
      molecules; however, the mechanism of catalysis is only partially characterized.
      These enzymes play critical roles in regulating cell growth, apoptosis,
      intracellular calcium oscillations, and post-synaptic vesicular trafficking. The
      UCLA fold recognition server (threader) predicted that the conserved 300-amino
      acid catalytic domain, common to all 5-phosphatases, adopts the fold of the
      apurinic/apyrimidinic (AP) base excision repair endonucleases. PSI-BLAST searches
      of GENPEPT, using the amino acid sequence of AP endonuclease exonuclease III,
      identified all members of the 5-phosphatase family with highly significant
      scores. A sequence alignment between exonuclease III and all known 5-phosphatases
      revealed six highly conserved motifs containing residues that corresponded to the
      catalytic residues in the AP endonucleases. Mutation of each of these residues to
      alanine in the mammalian 43-kDa, or yeast Inp52p 5-phosphatase, resulted in
      complete loss of enzyme activity. We predict the 5-phosphatase enzymes share a
      similar mechanism of catalysis to the AP endonucleases, consistent with other
      common functional similarities such as an absolute requirement for magnesium for
      activity. Based on this analysis, functional roles have been assigned to
      conserved residues in all 5-phosphatase enzymes.

PMID- 10962004
TI  - Structural differences of bacterial and mammalian K+ channels.
AB  - Using a peptide toxin, kaliotoxin (KTX), we gained new insight into the topology
      of the pore region of a voltage-gated potassium channel, mKv1.1. In order to find
      new interactions between mKv1.1 and KTX, we investigated the pH dependence of KTX
      block which was stronger at pH(o) 6.2 compared with pH(o) 7.4. Using site
      directed mutagenesis on the channel and the toxin, we found that protonation of
      His(34) in KTX caused the pH(o) dependence of KTX block. Glu(350) and Glu(353) in
      mKv1.1, which interact with His(34) in KTX, were calculated to be 4 and 7 A away
      from His(34)/KTX, respectively. Docking of KTX into a homology model of mKv1.1
      based on the KcsA crystal structure using this and other known interactions as
      constraints showed structural differences between mKv1.1 and KcsA within the
      turret (amino acids 348-357). To satisfy our data, we would have to modify the
      KcsA crystal structure for the mKv1.1 channel orienting Glu(350) 7 A and Glu(353)
      4 A more toward the center of the pore compared with KcsA. This would place
      Glu(350) 15 A and Glu(353) 11 A away from the center of the pore instead of the
      distances for the equivalent KcsA residues with 22 A for Gly(53) and 15 A for
      Gly(56), respectively. Bacterial and mammalian potassium channels may have
      structural differences regarding the turret of the outer pore vestibule. This
      topological difference between both channel types may have substantial influence
      on structure-guided development of new drugs for mammalian potassium channels by
      rational drug design.

PMID- 10962006
TI  - Functional roles of charged residues in the putative voltage sensor of the HCN2
      pacemaker channel.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to
      pacemaking activity in specialized neurons and cardiac myocytes. HCN channels
      have a structure similar to voltage-gated K(+) channels but have a much larger
      putative S4 transmembrane domain and open in response to membrane
      hyperpolarization instead of depolarization. As an initial attempt to define the
      structural basis of HCN channel gating, we have characterized the functional
      roles of the charged residues in the S2, S3, and S4 transmembrane domains. The
      nine basic residues and a single Ser in S4 were mutated individually to Gln, and
      the function of mutant channels was analyzed in Xenopus oocytes using two
      microelectrode voltage clamp techniques. Surface membrane expression of
      hemagglutinin-epitope-tagged channel proteins was examined by chemiluminescence.
      Our results suggest that 1) Lys-291, Arg-294, Arg-297, and Arg-300 contribute to
      the voltage dependence of gating but not to channel folding or trafficking to the
      surface membrane; 2) Lys-303 and Ser-306 are essential for gating, but not for
      channel folding/trafficking; 3) Arg-312 is important for folding but not gating;
      and 4) Arg-309, Arg-315, and Arg-318 are crucial for normal protein
      folding/trafficking and may charge-pair with Asp residues located in the S2 and
      S3 domains.

PMID- 10962005
TI  - Carboxyl-terminal fragments of Alzheimer beta-amyloid precursor protein
      accumulate in restricted and unpredicted intracellular compartments in presenilin
      1-deficient cells.
AB  - Absence of functional presenilin 1 (PS1) protein leads to loss of gamma-secretase
      cleavage of the amyloid precursor protein (betaAPP), resulting in a dramatic
      reduction in amyloid beta peptide (Abeta) production and accumulation of alpha-
      or beta-secretase-cleaved COOH-terminal fragments of betaAPP (alpha- or beta
      CTFs). The major COOH-terminal fragment (CTF) in brain was identified as betaAPP
      CTF-(11-98), which is consistent with the observation that cultured neurons
      generate primarily Abeta-(11-40). In PS1(-/-) murine neurons and fibroblasts
      expressing the loss-of-function PS1(D385A) mutant, CTFs accumulated in the
      endoplasmic reticulum, Golgi, and lysosomes, but not late endosomes. There were
      some subtle differences in the subcellular distribution of CTFs in PS1(-/-)
      neurons as compared with PS1(D385A) mutant fibroblasts. However, there was no
      obvious redistribution of full-length betaAPP or of markers of other organelles
      in either mutant. Blockade of endoplasmic reticulum-to-Golgi trafficking
      indicated that in PS1(-/-) neurons (as in normal cells) trafficking of betaAPP to
      the Golgi compartment is necessary before alpha- and beta-secretase cleavages
      occur. Thus, although we cannot exclude a specific role for PS1 in trafficking of
      CTFs, these data argue against a major role in general protein trafficking. These
      results are more compatible with a role for PS1 either as the actual gamma
      secretase catalytic activity or in other functions indirectly related to gamma
      secretase catalysis (e.g. an activator of gamma-secretase, a substrate adaptor
      for gamma-secretase, or delivery of gamma-secretase to betaAPP-containing
      compartments).

PMID- 10962007
TI  - A role of basic residues and the putative intercalating phenylalanine of the HMG
      1 box B in DNA supercoiling and binding to four-way DNA junctions.
AB  - HMG (high mobility group) 1 is a chromosomal protein with two homologous DNA
      binding domains, the HMG boxes A and B. HMG-1, like its individual HMG boxes, can
      recognize structural distortion of DNA, such as four-way DNA junctions (4WJs),
      that are very likely to have features common to their natural, yet unknown,
      cellular binding targets. HMG-1 can also bend/loop DNA and introduce negative
      supercoils in the presence of topoisomerase I in topologically closed DNAs.
      Results of our gel shift assays demonstrate that mutation of Arg(97) within the
      extended N-terminal strand of the B domain significantly (>50-fold) decreases
      affinity of the HMG box for 4WJs and alters the mode of binding without changing
      the structural specificity for 4WJs. Several basic amino acids of the extended N
      terminal strand (Lys(96)/Arg(97)) and helix I (Arg(110)/Lys(114)) of the B domain
      participate in DNA binding and supercoiling. The putative intercalating
      hydrophobic Phe(103) of helix I is important for DNA supercoiling but dispensable
      for binding to supercoiled DNA and 4WJs. We conclude that the B domain of HMG-1
      can tolerate substitutions of a number of amino acid residues without abolishing
      the structure-specific recognition of 4WJs, whereas mutations of most of these
      residues severely impair the topoisomerase I-mediated DNA supercoiling and change
      the sign of supercoiling from negative to positive.

PMID- 10962008
TI  - Ceramide directly activates protein kinase C zeta to regulate a stress-activated
      protein kinase signaling complex.
AB  - We have previously shown that interleukin 1 (IL-1)-receptor-generated ceramide
      induces growth arrest in smooth muscle pericytes by activating an upstream kinase
      in the stress-activated protein kinase (SAPK) cascade. We now report the
      mechanism by which ceramide activates the SAPK signaling pathway in human
      embryonic kidney cells (HEK-293). We demonstrate that ceramide activation of
      protein kinase C zeta (PKCzeta) mediates SAPK signal complex formation and
      subsequent growth suppression. Ceramide directly activates both
      immunoprecipitated and recombinant human PKCzeta in vitro. Additionally, ceramide
      activates SAPK activity, which is blocked with a dominant-negative mutant of
      PKCzeta. Co-immunoprecipitation studies reveal that ceramide induces the
      association of SAPK with PKCzeta, but not with PKCepsilon. In addition, ceramide
      treatment induces PKCzeta association with phosphorylated SEK and MEKK1, elements
      of the SAPK signaling complex. The biological role of ceramide to induce cell
      cycle arrest is mimicked by overexpression of a constitutively active PKCzeta.
      Together, these studies demonstrate that ceramide induces cell cycle arrest by
      enhancing the ability of PKCzeta to form a signaling complex with MEKK1, SEK, and
      SAPK.

PMID- 10962009
TI  - Activation of hepatocyte growth factor and urokinase/plasminogen activator by
      matriptase, an epithelial membrane serine protease.
AB  - Matriptase is an epithelial-derived, integral membrane serine protease. The
      enzyme was initially isolated from human breast cancer cells and has been
      implicated in breast cancer invasion and metastasis. In the current study, using
      active matriptase isolated from human milk, we demonstrate that matriptase is
      able to cleave various synthetic substrates with arginine or lysine as their P1
      sites and prefers small side chain amino acids, such as Ala and Gly, at P2 sites.
      For the most reactive substrates, N-tert-butoxycarbonyl (N-t-Boc)-gamma-benzyl
      Glu-Ala-Arg-7-amino-4-methylcoumarin (AMC) and N-t-Boc-Gln-Ala-Arg-AMC, the K(m)
      values were determined to be 3. 81 and 4.89 microm, respectively. We further
      demonstrated that matriptase can convert hepatocyte growth factor/scattering
      factor to its active form, which can induce scatter of Madin-Darby canine kidney
      epithelial cells and can activate c-Met tyrosine phosphorylation in A549 human
      lung carcinoma cells. In addition, we noted that matriptase can activate
      urokinase plasminogen activator but has no affect on plasminogen. These results
      suggest that matriptase could act as an epithelial, upstream membrane activator
      to recruit and activate stromal-derived downstream effectors important for
      extracellular matrix degradation and epithelial migration, two major events of
      tissue remodeling, cancer invasion, and metastasis.

PMID- 10962010
TI  - A point mutation in the pore region alters gating, Ca(2+) blockage, and
      permeation of olfactory cyclic nucleotide-gated channels.
AB  - Upon stimulation by odorants, Ca(2+) and Na(+) enter the cilia of olfactory
      sensory neurons through channels directly gated by cAMP. Cyclic nucleotide-gated
      channels have been found in a variety of cells and extensively investigated in
      the past few years. Glutamate residues at position 363 of the alpha subunit of
      the bovine retinal rod channel have previously been shown to constitute a cation
      binding site important for blockage by external divalent cations and to control
      single-channel properties. It has therefore been assumed, but not proven, that
      glutamate residues at the corresponding position of the other cyclic nucleotide
      gated channels play a similar role. We studied the corresponding glutamate (E340)
      of the alpha subunit of the bovine olfactory channel to determine its role in
      channel gating and in permeation and blockage by Ca(2+) and Mg(2+). E340 was
      mutated into either an aspartate, glycine, glutamine, or asparagine residue and
      properties of mutant channels expressed in Xenopus laevis oocytes were measured
      in excised patches. By single-channel recordings, we demonstrated that the open
      probabilities in the presence of cGMP or cAMP were decreased by the mutations,
      with a larger decrease observed on gating by cAMP. Moreover, we observed that the
      mutant E340N presented two conductance levels. We found that both external Ca(2+)
      and Mg(2+) powerfully blocked the current in wild-type and E340D mutants, whereas
      their blockage efficacy was drastically reduced when the glutamate charge was
      neutralized. The inward current carried by external Ca(2+) relative to Na(+) was
      larger in the E340G mutant compared with wild-type channels. In conclusion, we
      have confirmed that the residue at position E340 of the bovine olfactory CNG
      channel is in the pore region, controls permeation and blockage by external
      Ca(2+) and Mg(2+), and affects channel gating by cAMP more than by cGMP.

PMID- 10962011
TI  - The extracellular linker of muscle acetylcholine receptor channels is a gating
      control element.
AB  - We describe the functional consequences of mutations in the linker between the
      second and third transmembrane segments (M2-M3L) of muscle acetylcholine
      receptors at the single-channel level. Hydrophobic mutations (Ile, Cys, and Phe)
      placed near the middle of the linker of the alpha subunit (alphaS269) prolong
      apparent openings elicited by low concentrations of acetylcholine (ACh), whereas
      hydrophilic mutations (Asp, Lys, and Gln) are without effect. Because the gating
      kinetics of the alphaS269I receptor (a congenital myasthenic syndrome mutant) in
      the presence of ACh are too fast, choline was used as the agonist. This revealed
      an approximately 92-fold increased gating equilibrium constant, which is
      consistent with an approximately 10-fold decreased EC(50) in the presence of ACh.
      With choline, this mutation accelerates channel opening approximately 28-fold,
      slows channel closing approximately 3-fold, but does not affect agonist binding
      to the closed state. These ratios suggest that, with ACh, alphaS269I
      acetylcholine receptors open at a rate of approximately 1.4 x 10(6) s(-1) and
      close at a rate of approximately 760 s(-1). These gating rate constants, together
      with the measured duration of apparent openings at low ACh concentrations,
      further suggest that ACh dissociates from the diliganded open receptor at a rate
      of approximately 140 s(-1). Ile mutations at positions flanking alphaS269 impair,
      rather than enhance, channel gating. Inserting or deleting one residue from this
      linker in the alpha subunit increased and decreased, respectively, the apparent
      open time approximately twofold. Contrary to the alphaS269I mutation, Ile
      mutations at equivalent positions of the beta, straightepsilon, and delta
      subunits do not affect apparent open-channel lifetimes. However, in beta and
      straightepsilon, shifting the mutation one residue to the NH(2)-terminal end
      enhances channel gating. The overall results indicate that this linker is a
      control element whose hydrophobicity determines channel gating in a position- and
      subunit-dependent manner. Characterization of the transition state of the gating
      reaction suggests that during channel opening the M2-M3L of the alpha subunit
      moves before the corresponding linkers of the beta and straightepsilon subunits.

PMID- 10962012
TI  - COOH-terminal truncated alpha(1S) subunits conduct current better than full
      length dihydropyridine receptors.
AB  - Skeletal muscle dihydropyridine (DHP) receptors function both as voltage
      activated Ca(2+) channels and as voltage sensors for coupling membrane
      depolarization to release of Ca(2+) from the sarcoplasmic reticulum. In skeletal
      muscle, the principal or alpha(1S) subunit occurs in full-length ( approximately
      10% of total) and post-transcriptionally truncated ( approximately 90%) forms,
      which has raised the possibility that the two functional roles are subserved by
      DHP receptors comprised of different sized alpha(1S) subunits. We tested the
      functional properties of each form by injecting oocytes with cRNAs coding for
      full-length (alpha(1S)) or truncated (alpha(1SDeltaC)) alpha subunits. Both
      translation products were expressed in the membrane, as evidenced by increases in
      the gating charge (Q(max) 80-150 pC). Thus, oocytes provide a robust expression
      system for the study of gating charge movement in alpha(1S), unencumbered by
      contributions from other voltage-gated channels or the complexities of the
      transverse tubules. As in recordings from skeletal muscle, for heterologously
      expressed channels the peak inward Ba(2+) currents were small relative to Q(max).
      The truncated alpha(1SDeltaC) protein, however, supported much larger ionic
      currents than the full-length product. These data raise the possibility that DHP
      receptors containing the more abundant, truncated form of the alpha(1S) subunit
      conduct the majority of the L-type Ca(2+) current in skeletal muscle. Our data
      also suggest that the carboxyl terminus of the alpha(1S) subunit modulates the
      coupling between charge movement and channel opening.

PMID- 10962013
TI  - The EEEE locus is the sole high-affinity Ca(2+) binding structure in the pore of
      a voltage-gated Ca(2+) channel: block by ca(2+) entering from the intracellular
      pore entrance.
AB  - Selective permeability in voltage-gated Ca(2+) channels is dependent upon a
      quartet of pore-localized glutamate residues (EEEE locus). The EEEE locus is
      widely believed to comprise the sole high-affinity Ca(2+) binding site in the
      pore, which represents an overturning of earlier models that had postulated two
      high-affinity Ca(2+) binding sites. The current view is based on site-directed
      mutagenesis work in which Ca(2+) binding affinity was attenuated by single and
      double substitutions in the EEEE locus, and eliminated by quadruple alanine
      (AAAA), glutamine (QQQQ), or aspartate (DDDD) substitutions. However,
      interpretation of the mutagenesis work can be criticized on the grounds that EEEE
      locus mutations may have additionally disrupted the integrity of a second, non
      EEEE locus high-affinity site, and that such a second site may have remained
      undetected because the mutated pore was probed only from the extracellular pore
      entrance. Here, we describe the results of experiments designed to test the
      strength of these criticisms of the single high-affinity locus model of selective
      permeability in Ca(2+) channels. First, substituted-cysteine accessibility
      experiments indicate that pore structure in the vicinity of the EEEE locus is not
      extensively disrupted as a consequence of the quadruple AAAA mutations,
      suggesting in turn that the quadruple mutations do not distort pore structure to
      such an extent that a second high affinity site would likely be destroyed.
      Second, the postulated second high-affinity site was not detected by probing from
      the intracellularly oriented pore entrance of AAAA and QQQQ mutants. Using inside
      out patches, we found that, whereas micromolar Ca(2+) produced substantial block
      of outward Li(+) current in wild-type channels, internal Ca(2+) concentrations up
      to 1 mM did not produce detectable block of outward Li(+) current in the AAAA or
      QQQQ mutants. These results indicate that the EEEE locus is indeed the sole high
      affinity Ca(2+) binding locus in the pore of voltage-gated Ca(2+) channels.

PMID- 10962014
TI  - The molecular basis for Na-dependent phosphate transport in human erythrocytes
      and K562 cells.
AB  - The kinetics of sodium-stimulated phosphate flux and phosphate-stimulated sodium
      flux in human red cells have been previously described (Shoemaker, D.G., C.A.
      Bender, and R.B. Gunn. 1988. J. Gen. Physiol. 92:449-474). However, despite the
      identification of multiple isoforms in three gene families (Timmer, R.T., and
      R.B. Gunn. 1998. Am. J. Physiol. Cell Physiol. 274:C757-C769), the molecular
      basis for the sodium-phosphate cotransporter in erythrocytes is unknown. Most
      cells express multiple isoforms, thus disallowing explication of isoform-specific
      kinetics and function. We have found that erythrocyte membranes express one
      dominant isoform, hBNP-1, to which the kinetics can thus be ascribed. In
      addition, because the erythrocyte Na-PO(4) cotransporter can also mediate Li
      PO(4) cotransport, it has been suggested that this transporter functions as the
      erythrocyte Na-Li exchanger whose activity is systematically altered in patients
      with bipolar disease and patients with essential hypertension. To determine the
      molecular basis for the sodium-phosphate cotransporter, we reasoned that if the
      kinetics of phosphate transport in a nucleated erythroid-like cell paralleled
      those of the Na-activated pathway in anucleated erythrocytes and yet were
      distinct from those known for other Na-PO(4) cotransporters, then the expressed
      genes may be the same in both cell types. In this study, we show that the
      kinetics of sodium phosphate cotransport were similar in anuclear human
      erythrocytes and K562 cells, a human erythroleukemic cell line. Although the
      erythrocyte fluxes were 750-fold smaller, the half-activation concentrations for
      phosphate and sodium and the relative cation specificities for activation of
      (32)PO(4) influx were similar. Na-activation curves for both cell types showed
      cooperativity consistent with the reported stoichiometry of more than one Na
      cotransported per PO(4). In K562 cells, external lithium activation of phosphate
      influx was also cooperative. Inhibition by arsenate, K(I) = 2.6-2.7 mM, and
      relative inhibition by amiloride, amiloride analogs, phosphonoformate, and
      phloretin were similar. These characteristics were different from those reported
      for hNaPi-3 and hPiT-1 in other systems. PCR analysis of sodium-phosphate
      cotransporter isoforms in K562 cells demonstrated the presence of mRNAs for hPiT
      1, hPiT-2, and hBNP-1. The mRNAs for hNaPi-10 and hNaPi-3, the other two known
      isoforms, were absent. Western analysis of erythrocytes and K562 cells with
      isoform-specific antibodies detected the presence of only hBNP-1, an isoform
      expressed in brain neurons and glia. The similarities in the kinetics and the
      expression of only hBNP-1 protein in the two cell types is strong evidence that
      hBNP-1 is the erythrocyte and K562 cell sodium-phosphate cotransporter.

PMID- 10962015
TI  - MinK subdomains that mediate modulation of and association with KvLQT1.
AB  - KvLQT1 is a voltage-gated potassium channel expressed in cardiac cells that is
      critical for myocardial repolarization. When expressed alone in heterologous
      expression systems, KvLQT1 channels exhibit a rapidly activating potassium
      current that slowly deactivates. MinK, a 129 amino acid protein containing one
      transmembrane-spanning domain modulates KvLQT1, greatly slowing activation,
      increasing current amplitude, and removing inactivation. Using deletion and
      chimeric analysis, we have examined the structural determinants of MinK effects
      on gating modulation and subunit association. Coexpression of KvLQT1 with a MinK
      COOH-terminus deletion mutant (MinK DeltaCterm) in Xenopus oocytes resulted in a
      rapidly activated potassium current closely resembling currents recorded from
      oocytes expressing KvLQT1 alone, indicating that this region is necessary for
      modulation. To determine whether MinK DeltaCterm was associated with KvLQT1, a
      functional tag (G55C) that confers susceptibility to partial block by external
      cadmium was engineered into the transmembrane domain of MinK DeltaCterm. Currents
      derived from coexpression of KvLQT1 with MinK DeltaCterm were cadmium sensitive,
      suggesting that MinK DeltaCterm does associate with KvLQT1, but does not modulate
      gating. To determine which MinK regions are sufficient for KvLQT1 association and
      modulation, chimeras were generated between MinK and the Na(+) channel beta1
      subunit. Chimeras between MinK and beta1 could only modulate KvLQT1 if they
      contained both the MinK transmembrane domain and COOH terminus, suggesting that
      the MinK COOH terminus alone is not sufficient for KvLQT1 modulation, and
      requires an additional, possibly associative interaction between the MinK
      transmembrane domain and KvLQT1. To identify the MinK subdomains necessary for
      gating modulation, deletion mutants were designed and coexpressed with KvLQT1. A
      MinK construct with amino acid residues 94-129 deleted retained the ability to
      modulate KvLQT1 gating, identifying the COOH-terminal region critical for gating
      modulation. Finally, MinK/MiRP1 (MinK related protein-1) chimeras were generated
      to investigate the difference between these two closely related subunits in their
      ability to modulate KvLQT1. The results from this analysis indicate that MiRP1
      cannot modulate KvLQT1 due to differences within the transmembrane domain. Our
      results allow us to identify the MinK subdomains that mediate KvLQT1 association
      and modulation.

PMID- 10962016
TI  - Regulation of cloned ATP-sensitive K channels by phosphorylation, MgADP, and
      phosphatidylinositol bisphosphate (PIP(2)): a study of channel rundown and
      reactivation.
AB  - Kir6.2 channels linked to the green fluorescent protein (GFP) (Kir6. 2-GFP) have
      been expressed alone or with the sulfonylurea receptor SUR1 in HEK293 cells to
      study the regulation of K(ATP) channels by adenine nucleotides,
      phosphatidylinositol bisphosphate (PIP(2)), and phosphorylation. Upon excision of
      inside-out patches into a Ca(2+)- and MgATP-free solution, the activity of Kir6.2
      GFP+SUR1 channels spontaneously ran down, first quickly within a minute, and then
      more slowly over tens of minutes. In contrast, under the same conditions, the
      activity of Kir6.2-GFP alone exhibited only slow rundown. Thus, fast rundown is
      specific to Kir6.2-GFP+SUR1 and involves SUR1, while slow rundown is a property
      of both Kir6.2-GFP and Kir6.2-GFP+SUR1 channels and is due, at least in part, to
      Kir6.2 alone. Kir6. 2-GFP+SUR1 fast phase of rundown was of variable amplitude
      and led to increased ATP sensitivity. Excising patches into a solution containing
      MgADP prevented this phenomenon, suggesting that fast rundown involves loss of
      MgADP-dependent stimulation conferred by SUR1. With both Kir6.2-GFP and Kir6.2
      GFP+SUR1, the slow phase of rundown led to further increase in ATP sensitivity.
      Ca(2+) accelerated this process, suggesting a role for PIP(2) hydrolysis mediated
      by a Ca(2+)-dependent phospholipase C. PIP(2) could reactivate channel activity
      after a brief exposure to Ca(2+), but not after prolonged exposure. However, in
      both cases, PIP(2) reversed the increase in ATP sensitivity, indicating that
      PIP(2) lowers the ATP sensitivity by increasing P(o) as well as by decreasing the
      channel affinity for ATP. With Kir6.2-GFP+SUR1, slow rundown also caused loss of
      MgADP stimulation and sulfonylurea inhibition, suggesting functional uncoupling
      of SUR1 from Kir6.2-GFP. Ca(2+) facilitated the loss of sensitivity to MgADP, and
      thus uncoupling of the two subunits. The nonselective protein kinase inhibitor H
      7 and the selective PKC inhibitor peptide 19-36 evoked, within 5-15 min,
      increased ATP sensitivity and loss of reactivation by PIP(2) and MgADP.
      Phosphorylation of Kir6.2 may thus be required for the channel to remain PIP(2)
      responsive, while phosphorylation of Kir6.2 and/or SUR1 is required for
      functional coupling. In summary, short-term regulation of Kir6.2+SUR1 channels
      involves MgADP, while long-term regulation requires PIP(2) and phosphorylation.

PMID- 10962017
TI  - Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel
      gating energetics. Mechanisms of enhanced Ca(2+) sensitivity.
AB  - Over the past few years, it has become clear that an important mechanism by which
      large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) activity is regulated is
      the tissue-specific expression of auxiliary beta subunits. The first of these to
      be identified, beta1, is expressed predominately in smooth muscle and causes
      dramatic effects, increasing the apparent affinity of the channel for Ca(2+) 10
      fold at 0 mV, and shifting the range of voltages over which the channel activates
      -80 mV at 9.1 microM Ca(2+). With this study, we address the question: which
      aspects of BK(Ca) gating are altered by beta1 to bring about these effects:
      Ca(2+) binding, voltage sensing, or the intrinsic energetics of channel opening?
      The approach we have taken is to express the beta1 subunit together with the
      BK(Ca) alpha subunit in Xenopus oocytes, and then to compare beta1's steady state
      effects over a wide range of Ca(2+) concentrations and membrane voltages to those
      predicted by allosteric models whose parameters have been altered to mimic
      changes in the aspects of gating listed above. The results of our analysis
      suggest that much of beta1's steady state effects can be accounted for by a
      reduction in the intrinsic energy the channel must overcome to open and a
      decrease in its voltage sensitivity, with little change in the affinity of the
      channel for Ca(2+) when it is either open or closed. Interestingly, however, the
      small changes in Ca(2+) binding affinity suggested by our analysis (K(c) 7.4
      microM --> 9.6 microM; K(o) = 0.80 microM --> 0.65 microM) do appear to be
      functionally important. We also show that beta1 affects the mSlo conductance
      voltage relation in the essential absence of Ca(2+), shifting it +20 mV and
      reducing its apparent gating charge 38%, and we develop methods for
      distinguishing between alterations in Ca(2+) binding and other aspects of BK(Ca)
      channel gating that may be of general use.

PMID- 10962018
TI  - Fast and slow gating relaxations in the muscle chloride channel CLC-1.
AB  - Gating of the muscle chloride channel CLC-1 involves at least two processes
      evidenced by double-exponential current relaxations when stepping the voltage to
      negative values. However, there is little information about the gating of CLC-1
      at positive voltages. Here, we analyzed macroscopic gating of CLC-1 over a large
      voltage range (from -160 to +200 mV). Activation was fast at positive voltages
      but could be easily followed using envelope protocols that employed a tail pulse
      to -140 mV after stepping the voltage to a certain test potential for increasing
      durations. Activation was biexponential, demonstrating the presence of two gating
      processes. Both time constants became exponentially faster at positive voltages.
      A similar voltage dependence was also seen for the fast gate time constant of CLC
      0. The voltage dependence of the time constant of the fast process of CLC-1,
      tau(f), was steeper than that of the slow one, tau(s) (apparent activation
      valences were z(f) approximately -0. 79 and z(s) approximately -0.42) such that
      at +200 mV the two processes became kinetically distinct by almost two orders of
      magnitude (tau(f) approximately 16 micros, tau(s) approximately 1 ms). This
      voltage dependence is inconsistent with a previously published gating model for
      CLC-1 (Fahlke, C., A. Rosenbohm, N. Mitrovic, A.L. George, and R. Rudel. 1996.
      Biophys. J. 71:695-706). The kinetic difference at 200 mV allowed us to separate
      the steady state open probabilities of the two processes assuming that they
      reflect two parallel (not necessarily independent) gates that have to be open
      simultaneously to allow ion conduction. Both open probabilities could be
      described by Boltzmann functions with gating valences around one and with nonzero
      "offsets" at negative voltages, indicating that the two "gates" never close
      completely. For comparison with single channel data and to correlate the two
      gating processes with the two gates of CLC-0, we characterized their voltage,
      pH(int), and [Cl](ext) dependence, and the dominant myotonia inducing mutation,
      I290M. Assuming a double-barreled structure of CLC-1, our results are consistent
      with the identification of the fast and slow gating processes with the single
      pore and the common-pore gate, respectively.

PMID- 10962019
TI  - How to force conformity on transmitter-gated channels.

PMID- 10962020
TI  - Fundamental gating mechanism of nicotinic receptor channel revealed by mutation
      causing a congenital myasthenic syndrome.
AB  - We describe the genetic and kinetic defects in a congenital myasthenic syndrome
      due to the mutation epsilonA411P in the amphipathic helix of the acetylcholine
      receptor (AChR) epsilon subunit. Myasthenic patients from three unrelated
      families are either homozygous for epsilonA411P or are heterozygous and harbor a
      null mutation in the second epsilon allele, indicating that epsilonA411P is
      recessive. We expressed human AChRs containing wild-type or A411P epsilon
      subunits in 293HEK cells, recorded single channel currents at high bandwidth, and
      determined microscopic rate constants for individual channels using hidden Markov
      modeling. For individual wild-type and mutant channels, each rate constant
      distributes as a Gaussian function, but the spread in the distributions for
      channel opening and closing rate constants is greatly expanded by epsilonA411P.
      Prolines engineered into positions flanking residue 411 of the epsilon subunit
      greatly increase the range of activation kinetics similar to epsilonA411P,
      whereas prolines engineered into positions equivalent to epsilonA411 in beta and
      delta subunits are without effect. Thus, the amphipathic helix of the epsilon
      subunit stabilizes the channel, minimizing the number and range of kinetic modes
      accessible to individual AChRs. The findings suggest that analogous stabilizing
      structures are present in other ion channels, and possibly allosteric proteins in
      general, and that they evolved to maintain uniformity of activation episodes. The
      findings further suggest that the fundamental gating mechanism of the AChR
      channel can be explained by a corrugated energy landscape superimposed on a
      steeply sloped energy well.

PMID- 10962021
TI  - Immobilizing the moving parts of voltage-gated ion channels.
AB  - Voltage-gated ion channels have at least two classes of moving parts, voltage
      sensors that respond to changes in the transmembrane potential and gates that
      create or deny permeant ions access to the conduction pathway. To explore the
      coupling between voltage sensors and gates, we have systematically immobilized
      each using a bifunctional photoactivatable cross-linker, benzophenone-4
      carboxamidocysteine methanethiosulfonate, that can be tethered to cysteines
      introduced into the channel protein by mutagenesis. To validate the method, we
      first tested it on the inactivation gate of the sodium channel. The benzophenone
      labeled inactivation gate of the sodium channel can be trapped selectively either
      in an open or closed state by ultraviolet irradiation at either a hyperpolarized
      or depolarized voltage, respectively. To verify that ultraviolet light can
      immobilize S4 segments, we examined its relative effects on ionic and gating
      currents in Shaker potassium channels, labeled at residue 359 at the
      extracellular end of the S4 segment. As predicted by the tetrameric stoichiometry
      of these potassium channels, ultraviolet irradiation reduces ionic current by
      approximately the fourth power of the gating current reduction, suggesting little
      cooperativity between the movements of individual S4 segments. Photocross-linking
      occurs preferably at hyperpolarized voltages after labeling residue 359,
      suggesting that depolarization moves the benzophenone adduct out of a restricted
      environment. Immobilization of the S4 segment of the second domain of sodium
      channels prevents channels from opening. By contrast, photocross-linking the S4
      segment of the fourth domain of the sodium channel has effects on both activation
      and inactivation. Our results indicate that specific voltage sensors of the
      sodium channel play unique roles in gating, and suggest that movement of one
      voltage sensor, the S4 segment of domain 4, is at least a two-step process, each
      step coupled to a different gate.

PMID- 10962022
TI  - Severed channels probe regulation of gating of cystic fibrosis transmembrane
      conductance regulator by its cytoplasmic domains.
AB  - Opening and closing of a CFTR Cl(-) channel is controlled by PKA-mediated
      phosphorylation of its cytoplasmic regulatory (R) domain and by ATP binding, and
      likely hydrolysis, at its two nucleotide binding domains. Functional interactions
      between the R domain and the two nucleotide binding domains were probed by
      characterizing the gating of severed CFTR channels expressed in Xenopus oocytes.
      Expression levels were assessed using measurements of oocyte conductance, and
      detailed functional characteristics of the channels were extracted from kinetic
      analyses of macroscopic current relaxations and of single-channel gating events
      in membrane patches excised from the oocytes. The kinetic behavior of wild-type
      (WT) CFTR channels was compared with that of split CFTR channels bearing a single
      cut (between residues 633 and 634) just before the R domain, of split channels
      with a single cut (between residues 835 and 837) just after the R domain, and of
      split channels from which the entire R domain (residues 634-836) between those
      two cut sites was omitted. The channels cut before the R domain had
      characteristics almost identical to those of WT channels, except for less than
      twofold shorter open burst durations in the presence of PKA. Channels cut just
      after the R domain were characterized by a low level of activity even without
      phosphorylation, strong stimulation by PKA, enhanced apparent affinity for ATP as
      assayed by open probability, and a somewhat destabilized binding site for the
      locking action of the nonhydrolyzable ATP analog AMPPNP. Split channels with no R
      domain (from coexpression of CFTR segments 1-633 and 837-1480) were highly active
      without phosphorylation, but otherwise displayed the characteristics of channels
      cut after the R domain, including higher apparent ATP affinity, and less tight
      binding of AMPPNP at the locking site, than for WT. Intriguingly, severed
      channels with no R domain were still noticeably stimulated by PKA, implying that
      activation of WT CFTR by PKA likely also includes some component unrelated to the
      R domain. As the maximal opening rates were the same for WT channels and split
      channels with no R domain, it seems that the phosphorylated R domain does not
      stimulate opening of CFTR channels; rather, the dephosphorylated R domain
      inhibits them.

PMID- 10962023
TI  - Cellulose-binding domains promote hydrolysis of different sites on crystalline
      cellulose.
AB  - The cohesin-dockerin interaction in Clostridium thermocellum cellulosome mediates
      the tight binding of cellulolytic enzymes to the cellulosome-integrating protein
      CipA. Here, this interaction was used to study the effect of different cellulose
      binding domains (CBDs) on the enzymatic activity of C. thermocellum endoglucanase
      CelD (1,4-beta-d endoglucanase, EC) toward various cellulosic substrates. The
      seventh cohesin domain of CipA was fused to CBDs originating from the Trichoderma
      reesei cellobiohydrolases I and II (CBD(CBH1) and CBD(CBH2)) (1,4-beta-d glucan
      cellobiohydrolase, EC), from the Cellulomonas fimi xylanase/exoglucanase Cex
      (CBD(Cex)) (beta-1,4-d glucanase, EC), and from C. thermocellum CipA (CBD(CipA)).
      The CBD-cohesin hybrids interacted with the dockerin domain of CelD, leading to
      the formation of CelD-CBD complexes. Each of the CBDs increased the fraction of
      cellulose accessible to hydrolysis by CelD in the order CBD(CBH1) < CBD(CBH2)
      approximately CBD(Cex) < CBD(CipA). In all cases, the extent of hydrolysis was
      limited by the disappearance of sites accessible to CelD. Addition of a batch of
      fresh cellulose after completion of the reaction resulted in a new burst of
      activity, proving the reversible binding of the intact complexes despite the
      apparent binding irreversibility of some CBDs. Furthermore, burst of activity
      also was observed upon adding new batches of CelD-CBD complexes that contained a
      CBD differing from the first one. This complementation between different CBDs
      suggests that the sites made available for hydrolysis by each of the CBDs are at
      least partially nonoverlapping. The only exception was CBD(CipA), whose sites
      appeared to overlap all of the other sites.

PMID- 10962024
TI  - Act1, an NF-kappa B-activating protein.
AB  - Use of an NF-kappaB-dependent selectable marker facilitated the isolation of a
      cell line containing a cDNA encoding Act1, an NF-kappaB activator. Act1
      associates with and activates IkappaB kinase (IKK), leading to the liberation of
      NF-kappaB from its complex with IkappaB. Many signaling pathways that liberate NF
      kappaB also activate activating transcription factor (ATF) and activator protein
      1 (AP-1) through Jun kinase (JNK). Act1 also activates JNK, suggesting that it
      might be part of a multifunctional complex involved in the activation of both NF
      kappaB and JNK. Act1 fails to activate NF-kappaB in an IL-1-unresponsive mutant
      cell line in which all known signaling components are present, suggesting that it
      interacts with an unknown component in IL-1 signaling.

PMID- 10962025
TI  - Expression and parent-of-origin effects for FIS2, MEA, and FIE in the endosperm
      and embryo of developing Arabidopsis seeds.
AB  - The promoters of MEA (FIS1), FIS2, and FIE (FIS3), genes that repress seed
      development in the absence of pollination, were fused to beta-glucuronidase (GUS)
      to study their activity pattern. The FIS2GUS product is found in the embryo sac,
      in each of the polar cell nuclei, and in the central cell nucleus. After
      pollination, the maternally derived FIS2GUS protein occurs in the nuclei of the
      cenocytic endosperm. Before cellularization of the endosperm, activity is
      terminated in the micropylar and central nuclei of the endosperm and subsequently
      in the nuclei of the chalazal cyst. MEAGUS has a pattern of activity similar to
      that of FIS2GUS, but FIEGUS protein is found in many tissues, including the
      prepollination embryo sac, and in embryo and endosperm postpollination. The
      similarity in mutant phenotypes; the activity of FIE, MEA, and FIS2 in the same
      cells in the embryo sac; and the fact that MEA and FIE proteins interact in a
      yeast two-hybrid system suggest that these proteins operate in the same system of
      control of seed development. Maternal and not paternal FIS2GUS, MEAGUS, and
      FIEGUS show activity in early endosperm, so these genes may be imprinted. When
      fis2, mea, and fie mutants are pollinated, seed development is arrested at the
      heart embryo stage. The seed arrest of mea and fis2 is avoided when they are
      fertilized by a low methylation parent. The wild-type alleles of MEA or FIS2 are
      not required. The parent-of-origin-determined differential activity of MEA, FIS2,
      and FIE is not dependent on DNA methylation, but methylation does control some
      gene(s) that have key roles in seed development.

PMID- 10962027
TI  - The importance of being discrete: life always wins on the surface.
AB  - Many systems in chemistry, biology, finance, and social sciences present emerging
      features that are not easy to guess from the elementary interactions of their
      microscopic individual components. In the past, the macroscopic behavior of such
      systems was modeled by assuming that the collective dynamics of microscopic
      components can be effectively described collectively by equations acting on
      spatially continuous density distributions. It turns out that, to the contrary,
      taking into account the actual individual/discrete character of the microscopic
      components of these systems is crucial for explaining their macroscopic behavior.
      In fact, we find that in conditions in which the continuum approach would predict
      the extinction of all of the population (respectively the vanishing of the
      invested capital or the concentration of a chemical substance, etc.), the
      microscopic granularity insures the emergence of macroscopic localized
      subpopulations with collective adaptive properties that allow their survival and
      development. In particular it is found that in two dimensions "life" (the
      localized proliferating phase) always prevails.

PMID- 10962026
TI  - Differential requirement of the cytoplasmic subregions of gamma c chain in T cell
      development and function.
AB  - The common cytokine receptor gamma chain (gammac), a shared component of the
      receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the development
      and function of lymphocytes. The cytoplasmic domain of gammac consists of 85 aa,
      in which the carboxyl-terminal 48 aa are essential for its interaction with and
      activation of the Janus kinase, Jak3. Evidence has been provided that Jak3
      independent signals might be transmitted via the residual membrane-proximal
      region; however, its role in vivo remains totally unknown. In the present study,
      we expressed mutant forms of gammac, which lack either most of the cytoplasmic
      domain or only the membrane-distal Jak3-binding region, on a gammac null
      background. We demonstrate that, unlike gammac or Jak3 null mice, expression of
      the latter, but not the former mutant, restores T lymphopoiesis in vivo,
      accompanied by strong expression of Bcl-2. On the other hand, the in vitro
      functions of the restored T cells still remained impaired. These results not only
      reveal the hitherto unknown role of the gammac membrane-proximal region, but also
      suggest the differential requirement of the cytoplasmic subregions of gammac in T
      cell development and function.

PMID- 10962028
TI  - Nutritional regulation of the fatty acid synthase promoter in vivo: sterol
      regulatory element binding protein functions through an upstream region
      containing a sterol regulatory element.
AB  - The transcription of fatty acid synthase (FAS), a central enzyme in de novo
      lipogenesis, is dramatically induced by fasting/refeeding and insulin. We
      reported that upstream stimulatory factor binding to the -65 E-box is required
      for induction of the FAS transcription by insulin in 3T3-L1 adipocytes. On the
      other hand, we recently found that two upstream 5' regions are required for
      induction in vivo by fasting/refeeding and insulin; one at -278 to -131 albeit at
      a low level, and the other at -444 to -278 with an E-box at -332 where upstream
      stimulatory factor functions for maximal induction. Here, we generated double
      transgenic mice carrying the chloramphenicol acetyltransferase reporter driven by
      the various 5' deletions of the FAS promoter region and a truncated active form
      of the sterol regulatory element (SRE) binding protein (SREBP)-1a. We found that
      SREBP participates in the nutritional regulation of the FAS promoter and that the
      region between -278 and -131 bp is required for SREBP function. We demonstrate
      that SREBP binds the -150 canonical SRE present between -278 and -131, and SREBP
      can function through the -150 SRE in cultured cells. These in vivo and in vitro
      results indicate that SREBP is involved in the nutritional induction of the FAS
      promoter via the -278/-131 region and that the -150 SRE is the target sequence.

PMID- 10962029
TI  - A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad
      interaction in cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD), an autosomal-dominant human bone disease, is
      thought to be caused by heterozygous mutations in runt-related gene 2
      (RUNX2)/polyomavirus enhancer binding protein 2alphaA (PEBP2alphaA)/core-binding
      factor A1 (CBFA1). To understand the mechanism underlying the pathogenesis of
      CCD, we studied a novel mutant of RUNX2, CCDalphaA376, originally identified in a
      CCD patient. The nonsense mutation, which resulted in a truncated RUNX2 protein,
      severely impaired RUNX2 transactivation activity. We show that signal transducers
      of transforming growth factor beta superfamily receptors, Smads, interact with
      RUNX2 in vivo and in vitro and enhance the transactivation ability of this
      factor. The truncated RUNX2 protein failed to interact with and respond to Smads
      and was unable to induce the osteoblast-like phenotype in C2C12 myoblasts on
      stimulation by bone morphogenetic protein. Therefore, the pathogenesis of CCD may
      be related to the impaired Smad signaling of transforming growth factor beta/bone
      morphogenetic protein pathways that target the activity of RUNX2 during bone
      formation.

PMID- 10962030
TI  - Human renal cell carcinoma expresses distinct binding sites for growth hormone
      releasing hormone.
AB  - Antagonists of growth hormone-releasing hormone (GHRH) inhibit the proliferation
      of various human cancers in vitro and in vivo by mechanisms that include apparent
      direct effects through specific binding sites expressed on tumors and that differ
      from pituitary human GHRH (hGHRH) receptors. In this study, GHRH antagonist JV-1
      38 (20 microgram/day per animal s.c.) inhibited the growth of orthotopic CAKI-1
      human renal cell carcinoma (RCC) by 83% and inhibited the development of
      metastases to lung and lymph nodes. Using ligand competition assays with (125)I
      labeled GHRH antagonist JV-1-42, we demonstrated the presence of specific high
      affinity (K(d) = 0.25 +/- 0.03 nM) binding sites for GHRH with a maximal binding
      capacity (B(max)) of 70.2 +/- 4.1 fmol/mg of membrane protein in CAKI-1 tumors.
      These receptors bind GHRH antagonists preferentially and display a lower affinity
      for hGHRH. The binding of (125)I-JV-1-42 is not inhibited by vasoactive
      intestinal peptide (VIP)-related peptides sharing structural homology with hGHRH.
      The receptors for GHRH antagonists on CAKI-1 tumors are distinct from binding
      sites detected with (125)I-VIP (K(d) = 0.89 +/- 0.14 nM; B(max) = 183.5 +/- 2.6
      fmol/mg of protein) and also have different characteristics from GHRH receptors
      on rat pituitary as documented by the insignificant binding of [His(1),(125)I
      Tyr(10), Nle(27)]hGHRH(1-32)NH(2). Reverse transcription-PCR revealed the
      expression of splice variants of hGHRH receptor in CAKI-1 RCC. Biodistribution
      studies demonstrate an in vivo uptake of (125)I-JV-1-42 by the RCC tumor tissue.
      The presence of specific receptor proteins that bind GHRH antagonists in CAKI-1
      RCC supports the view that distinct binding sites that mediate the inhibitory
      effect of GHRH antagonists are present on various human cancers.

PMID- 10962031
TI  - Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing
      hormone receptors from human cancers.
AB  - The proliferation of various tumors is inhibited by the antagonists of growth
      hormone-releasing hormone (GHRH) in vitro and in vivo, but the receptors
      mediating the effects of GHRH antagonists have not been identified so far. Using
      an approach based on PCR, we detected two major splice variants (SVs) of mRNA for
      human GHRH receptor (GHRH-R) in human cancer cell lines, including LNCaP
      prostatic, MiaPaCa-2 pancreatic, MDA-MB-468 breast, OV-1063 ovarian, and H-69
      small-cell lung carcinomas. In addition, high-affinity, low-capacity binding
      sites for GHRH antagonists were found on the membranes of cancer cell lines such
      as MiaPaCa-2 that are negative for the vasoactive intestinal peptide/pituitary
      adenylate cyclase-activating polypeptide receptor (VPAC-R) or lines such as LNCaP
      that are positive for VPAC-R. Sequence analysis of cDNAs revealed that the first
      three exons in SV(1) and SV(2) are replaced by a fragment of retained intron 3
      having a new putative in-frame start codon. The rest of the coding region of
      SV(1) is identical to that of human pituitary GHRH-R, whereas in SV(2) exon 7 is
      spliced out, resulting in a 1-nt upstream frameshift, which leads to a premature
      stop codon in exon 8. The intronic sequence may encode a distinct 25-aa fragment
      of the N-terminal extracellular domain, which could serve as a proposed signal
      peptide. The continuation of the deduced protein sequence coded by exons 4-13 in
      SV(1) is identical to that of pituitary GHRH-R. SV(2) may encode a GHRH-R isoform
      truncated after the second transmembrane domain. Thus SVs of GHRH-Rs have now
      been identified in human extrapituitary cells. The findings support the view that
      distinct receptors are expressed on human cancer cells, which may mediate the
      antiproliferative effect of GHRH antagonists.

PMID- 10962032
TI  - Mapping the parameters of prion-induced neuropathology.
AB  - We present a theoretical framework that enables us to dissect out the parametric
      dependencies of the pathogenesis of prion diseases. We are able to determine the
      influence of both host-dependent factors (connectivity, cell density, protein
      synthesis rate, and cell death) and strain-dependent factors (cell tropism,
      virulence, and replication rate). We use a model based on a linked system of
      differential equations on a lattice to explore how the regional distribution of
      central nervous system pathology in Creutzfeldt-Jakob disease, Gerstmann
      Straussler-Scheinker syndrome, and fatal familial insomnia relates to each of
      these factors. The model then is used to make qualitative predictions about the
      pathology for two possible hypothetical triggers of neuronal loss in prion
      diseases. Pathological progression in overexpressing mouse models has been shown
      to depend on the site of initial infection. The model allows us to compare the
      pathologies resulting from different inoculation routes.

PMID- 10962034
TI  - NMR reveals hydrogen bonds between oxygen and distal histidines in oxyhemoglobin.
AB  - Compared with free heme, the proteins hemoglobin (Hb) and myoglobin (Mb) exhibit
      greatly enhanced affinity for oxygen relative to carbon monoxide. This
      physiologically vital property has been attributed to either steric hindrance of
      CO or stabilization of O(2) binding by a hydrogen bond with the distal histidine.
      We report here the first direct evidence of such a hydrogen bond in both alpha-
      and beta-chains of oxyhemoglobin, as revealed by heteronuclear NMR spectra of
      chain-selectively labeled samples. Using these spectra, we have assigned the
      imidazole ring (1)H and (15)N chemical shifts of the proximal and distal
      histidines in both carbonmonoxy- and oxy-Hb. Because of their proximity to the
      heme, these chemical shifts are extremely sensitive to the heme pocket
      conformation. Comparison of the measured chemical shifts with values predicted
      from x-ray structures suggests differences between the solution and crystal
      structures of oxy-Hb. The chemical shift discrepancies could be accounted for by
      very small displacements of the proximal and distal histidines. This suggests
      that NMR could be used to obtain very high-resolution heme pocket structures of
      Hb, Mb, and other heme proteins.

PMID- 10962033
TI  - CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.
AB  - Pathogens, inflammatory signals, and stress cause acute transcriptional responses
      in cells. The induced expression of genes in response to these signals invariably
      involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation
      of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases
      (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein
      kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two
      catalytic subunits of a core IKK complex that also contains the regulatory
      subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is
      essential for activation of the IKKs, but its mechanism of action is not known.
      Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK),
      a previously unknown protein that directly interacts with NEMO/IKKgamma in cells.
      When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it
      transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is
      prevented in the presence of kinase-deficient, interfering mutants of the IKKs.
      CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules.
      CIKS could coordinate the activation of two stress-induced signaling pathways,
      functions reminiscent of those noted for tumor necrosis factor receptor
      associated factor adaptor proteins.

PMID- 10962035
TI  - Anterograde flow of cargo across the golgi stack potentially mediated via
      bidirectional "percolating" COPI vesicles.
AB  - How do secretory proteins and other cargo targeted to post-Golgi locations
      traverse the Golgi stack? We report immunoelectron microscopy experiments
      establishing that a Golgi-restricted SNARE, GOS 28, is present in the same
      population of COPI vesicles as anterograde cargo marked by vesicular stomatitis
      virus glycoprotein, but is excluded from the COPI vesicles containing retrograde
      targeted cargo (marked by KDEL receptor). We also report that GOS 28 and its
      partnering t-SNARE heavy chain, syntaxin 5, reside together in every cisterna of
      the stack. Taken together, these data raise the possibility that the anterograde
      cargo-laden COPI vesicles, retained locally by means of tethers, are inherently
      capable of fusing with neighboring cisternae on either side. If so, quanta of
      exported proteins would transit the stack in GOS 28-COPI vesicles via a
      bidirectional random walk, entering at the cis face and leaving at the trans face
      and percolating up and down the stack in between. Percolating vesicles carrying
      both post-Golgi cargo and Golgi residents up and down the stack would reconcile
      disparate observations on Golgi transport in cells and in cell-free systems.

PMID- 10962036
TI  - From the cover: nanoscale imaging of chemical interactions: fluorine on graphite.
AB  - Using C60-functionalized scanning tunneling microscope tips, we have investigated
      the adsorption of fluorine on graphite. Based on characteristics of the
      accompanying electron standing waves, we are able to distinguish the fluorine
      adatoms that have bonded ionically to the graphite surface from those that have
      formed covalent bonds with the surface. This result permits determination of the
      ratio of ionic to covalent C-F bonds on graphite obtained by gas phase
      fluorination, which seems to be temperature-independent between 200 and 300
      degrees C under the reaction conditions used.

PMID- 10962037
TI  - Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts.
AB  - Overexpression of the proto-oncogene MYC has been implicated in the genesis of
      diverse human cancers. One explanation for the role of MYC in tumorigenesis has
      been that this gene might drive cells inappropriately through the division cycle,
      leading to the relentless proliferation characteristic of the neoplastic
      phenotype. Herein, we report that the overexpression of MYC alone cannot sustain
      the division cycle of normal cells but instead leads to their arrest in G(2). We
      used an inducible form of the MYC protein to stimulate normal human and rodent
      fibroblasts. The stimulated cells passed through G(1) and S but arrested in G(2)
      and frequently became aneuploid, presumably as a result of inappropriate
      reinitiation of DNA synthesis. Absence of the tumor suppressor gene p53 or its
      downstream effector p21 reduced the frequency of both G(2) arrest and aneuploidy,
      apparently by compromising the G(2) checkpoint control. Thus, relaxation of the
      G(2) checkpoint may be an essential early event in tumorigenesis by MYC. The loss
      of p53 function seems to be one mechanism by which this relaxation commonly
      occurs. These findings dramatize how multiple genetic events can collaborate to
      produce neoplastic cells.

PMID- 10962038
TI  - Twin-twin transfusion syndrome: an update.
AB  - Twin-twin transfusion syndrome leads to high rates of perinatal morbidity and
      mortality due to its poorly understood etiology and difficult diagnosing and
      treatment. Current therapies are suboptimal and have not been tested through
      randomized controlled trials. Parent counseling at the time of diagnosis includes
      informing on poor chance of double survival, relatively high chance of long term
      neurologic handicap, almost certain prematurity, and the probability of cesarean
      delivery. Improvement in therapies awaits a better scientific understanding of
      the etiology of this condition.

PMID- 10962040
TI  - Sonographic measurements of subcutaneous fetal fat in pregnancies complicated by
      gestational diabetes and in normal pregnancies.
AB  - AIM: To compare sonographic measurements of fetal fat tissue in pregnancies
      complicated by gestational diabetes (GD), with patients undergoing either a diet
      only or a combined diet and insulin treatment, to those obtained in pregnancies
      with a normal glucose challenge test. METHODS: Forty-five singleton pregnancies
      complicated by GD but free of any other maternal disease known to affect fetal
      growth were recruited. GD was diagnosed by a 3-hour OGTT, and treatment was
      differentiated according to the glycemic profile. GD mothers were divided into
      two treatment groups: glycemic profile normalized by diet only treatment (n=16)
      and by combined diet and insulin treatment (n=29). Fetal biometry and
      subcutaneous fat tissue thickness of the anterior abdominal wall were
      sonographically evaluated at the time of diagnosis and every 4 weeks afterwards
      in both GD and normal glucose challenge test group (n=25). RESULTS: No
      differences were found in neonatal outcomes between combined diet and insulin
      treatment group and normal cases, whereas neonatal weight showed a statistically
      significant difference between diet only treatment group and healthy population.
      Abdominal circumference in fetuses from GD mothers and normal fetuses was
      similar, but there was a difference in the fetal fat tissue thickness at the time
      of diagnosis. CONCLUSION: Increased fetal fat tissue thickness in GD mothers at
      recruitment and its growth rate reduction during adequate treatment may be a new
      criterion for direct estimation of fetal metabolic status instead of the
      traditional indirect evaluation based on maternal glucose concentrations.

PMID- 10962039
TI  - Vascular impedance of uterine, inferior vesicle, and ophthalmic arteries in
      postmenopausal women receiving hormonal replacement therapy: comparative Doppler
      study.
AB  - AIM: To investigate the effects of combined hormone replacement therapy (HRT) on
      vascular impedance of the uterine, the inferior vesicle, and the ophthalmic
      arteries. METHODS: Thirty-five postmenopausal patients were divided in two
      groups: 21 patients with 1-5 years of menopause and 14 patients with =6 years of
      menopause. Each group was examined in basal condition and after 1, 3, and 6
      months of HRT. Blood flow impedances of the uterine, the inferior vesicle, and
      the ophthalmic arteries were analyzed by color Doppler. Estradiol plasma
      concentrations were assayed on the day of Doppler examination. RESULTS: Analysis
      of the uterine and inferior vesicle arteries flow velocities showed a significant
      positive correlation between the resistance index (RI) and years of menopause.
      Higher impedance values were found in patients with longer menopause duration
      (p<0.05). In patients with =6 years of menopause, impedances of the uterine and
      the inferior vesicle arteries were 0. 94+/-0.03 and 0.91+/-0.04, respectively,
      whereas in patients with 1-5 years of menopause impedances were 0.89+/-0.04 and
      0.98+/-0.02, respectively. We noticed no significant correlation between baseline
      RI and duration of menopause at the level of the ophthalmic artery in either
      group (0.72 vs. 0.73, respectively; p<0.05). After six months of HRT, plasma
      estradiol concentrations inversely correlated with RI of the uterine (r=0.2556;
      p=0.021), the inferior vesicle (r=0.2653; p=0.023), and the ophthalmic (r=
      0.2211; p=0.017) arteries. CONCLUSION: Doppler studies of the uterine, the
      inferior vesicle, and the ophthalmic arteries can provide specific and precise
      pathophysiological information to assess blood flow variations in correlation
      with combined HRT.

PMID- 10962041
TI  - Clinical application of three-dimensional ultrasound in fetal brain assessment.
AB  - AIM: To clarify the usefulness of three-dimensional (3D) ultrasound in the
      assessment of the fetal head and brain, according to 3D ultrasound surface
      reconstruction, multiplanar image analysis, three-dimensional angiography, and
      volume calculation. METHODS: We examined 326 normal fetuses between 10 and 40
      weeks of gestation using 3D ultrasound (Voluson, 530D, Medison, Seoul, Korea),
      mainly with transvaginal 3D transducer. Fetal head structures, such as the skull,
      brain structure, and brain circulation, were presented by surface mode,
      multiplanar imaging mode, and three-dimensional Doppler mode. After automatic
      volume acquisition of the fetal head, image analyses were performed off-line, and
      3D View software was used for volume imaging of the lateral ventricle and choroid
      plexus in randomly selected 30 normal fetuses. Seven fetuses with intracranial
      abnormalities were evaluated by 3D ultrasound functions. RESULTS: Surface mode of
      3D ultrasound objectively depicted in vivo development of the cranial bones and
      formation of the cranial sutures and fontanelles in normal fetuses. Multiplanar
      image analysis of the brain structure presented a fetal brain in more cutting
      sections than conventional 2D ultrasound. Transvaginal 3D angiography was
      successful in 13% of normal fetuses and rotation of 3D circulatory image allowed
      the analysis of the intracranial vessels. Volume imaging showed the intracranial
      structures, such as the lateral ventricle and choroid plexus. Intracranial
      abnormalities were longitudinally evaluated by 3D ultrasound and objective images
      helped in reaching prenatal diagnoses. CONCLUSION: Advanced 3D ultrasonography
      and software for volume analysis can provide additional objective information
      about the fetal skull formation, brain structure, and brain circulation.

PMID- 10962042
TI  - Pulmonary stenosis in recipient twins in twin-to-twin transfusion syndrome:
      report on 3 cases and review of literature.
AB  - This report describes 3 cases of pulmonary stenosis in the recipient twin in twin
      twin transfusion syndrome. Fetal echocardiography showed cardiomegaly, tricuspid
      valve regurgitation, and increased reverse flow in the inferior vena cava, as
      signs of congestive heart failure in all 3 cases. We diagnosed 2 cases of
      pulmonary stenosis by fetal echocardiography prenatally and confirmed our
      findings in all 3 cases postnatally. Two cases underwent postnatal balloon
      valvuloplasty to release the pulmonary valvular stenosis in neonatal period. The
      third one died soon after delivery and autopsy showed a slightly thickened
      pulmonary valve. One of the cases was diagnosed in the early second trimester (20
      weeks of pregnancy), the earliest detection of fetal pulmonary stenosis reported
      in literature. The presence of high peak velocity of the pulmonary artery at 20
      weeks of pregnancy preceded the development of pulmonary stenosis in this case.
      This supports the hypothesis that alterations in fetal hemodynamics may result in
      structural cardiac abnormality.

PMID- 10962043
TI  - What do contrast media add to three-dimensional power Doppler evaluation of
      adnexal masses?
AB  - AIM: To investigate the potential usefulness of contrast-enhanced three
      dimensional (3D) power Doppler sonography in the differentiation of benign and
      malignant adnexal lesions. METHODS: Thirty one patients with complex adnexal
      lesions of uncertain malignancy at transvaginal B-mode and/or color Doppler
      sonography were prospectively evaluated with three-dimensional power Doppler
      sonography before and after injection of a contrast agent. Presence of a
      penetrating pattern and a mixed penetrating and/or peripheral pattern suggested
      adnexal malignancy. The results were compared with histopathologic findings.
      RESULTS: There were 10 cases of ovarian malignancy and 21 benign adnexal lesions.
      Of 10 ovarian cancers, 6 showed vascular distribution suggestive of malignancy at
      nonenhanced 3D power Doppler sonography. After injection of contrast agent, a
      penetrating vascular pattern and/or mixed penetrating and peripheral pattern were
      detected in all cases of ovarian malignancy as well as in 2 benign lesions
      (fibroma and cystadenofibroma), which were misdiagnosed as malignant. The use of
      contrast agent with three-dimensional power Doppler sonography showed diagnostic
      efficiency of 96.7%, superior to that of nonenhanced 3D power Doppler sonography
      (93.5%). CONCLUSION: Contrast-enhanced 3D power Doppler sonography provides
      better visualization of tumor vascularity in complex adnexal masses. If used
      together with 3D morphological ultrasound assessment, enhanced 3D power Doppler
      imaging may precisely discriminate benign from malignant adnexal lesions.

PMID- 10962044
TI  - Three-dimensional ultrasound for routine check-up in in vitro fertilization
      patients.
AB  - AIM: To determine whether three-dimensional ultrasound (3D US) improves diagnosis
      in patients undergoing in vitro fertilization (IVF). METHODS: Three-dimensional
      and power Doppler ultrasound were used in examination of 267 patients undergoing
      IVF on their first visit, during ovulation induction and aspiration of the
      oocytes. Patients with suspected uterine anomalies and/or abnormalities of the
      endometrium (N=108) were treated by operative hysteroscopy. On the day of oocyte
      collection, multiplanar imaging and 3D reconstruction demonstrated cumuli in
      follicles greater than 15 mm. Cumulus assessment inside the ovarian follicles was
      correlated to the number of mature oocytes. Power Doppler examination was
      performed when superposing vessels did not allow the puncture needle to be
      introduced correctly. RESULTS: The diagnosis was correct in all cases of
      endometrial polyp, submucous myoma, arcuate uteri, and septate uteri, as
      confirmed by office hysteroscopy. Intrauterine synechiae were correctly diagnosed
      preoperatively in one of the four cases. The mean (+/-SD) number of follicles >18
      mm was 8.2+/-5.8, and the total number of follicles demonstrating cumulus in all
      three planes was 6.4+/-5.1. The ratios of cumuli/retrieved oocytes,
      cumuli/fertilized oocytes, and cumuli/mature oocytes were 6.2+/-4.2, 5.4+/-2.8,
      and 5.9+/-2.6, respectively. CONCLUSION: 3D US improved recognition of the
      uterine anatomy, characterization of the surface features, assessment of the
      ovaries during stimulation cycles, and morphologic and functional evaluation of
      the anatomic structures of the inner reproductive organs, thus avoiding the need
      of invasive diagnostic procedures. Puncturing procedures, such as oocyte
      collection, can be performed more precisely.

PMID- 10962045
TI  - Nuchal translucency in multiple pregnancies.
AB  - AIM: To evaluate the prevalence of increased nuchal translucency (NT) in multiple
      pregnancies and its relation to fetal karyotype and pregnancy outcome. METHODS:
      We measured fetal nuchal translucency (NT) in 6,338 women pregnant from 10+3 to
      13+6 weeks by ultrasound and evaluated the prevalence of NT=95th centile in 115
      multiple pregnancies, including 100 pairs of twins (70 dichorionic and 30
      monochorionic placentas), 9 triplets, 5 quadruplets, and one quintuplet.
      Chorionicity, fetal karyotype, and pregnancy outcome were also evaluated in 400
      singleton pregnancies. RESULTS: NT=95th centile in a single fetus was found in
      10/70 cases of dichorionic twin pregnancies (14%), in two quadruplets, in 7/30
      monochorionic twin pregnancies (23.3%), and in both fetuses in one dichorionic
      twin pregnancy. In the control group, NT=95th centile was found in 17/400 (4.2%)
      cases. In multiple pregnancies, two cases of trisomy 21 and one of 47, XXY were
      found. NT=95th centile was found in 2/2 fetuses with trisomy 21 (one dichorionic
      twin pregnancy and one tetrachorionic pregnancy), but not in the 47, XXY trisomy
      (trichorionic triplet pregnancy). A skeletal dysplasia and a Goldenhar syndrome
      were found among the 10 dichorionic pregnancies with increased NT. Three
      intrauterine deaths of both fetuses, one congenital heart disease, and a case of
      twin-to-twin transfusion occurred in 7 monochorionic pregnancies with increased
      NT. CONCLUSION: Increased NT in multiple pregnancies indicates fetuses at risk of
      chromosomal abnormalities and fetal malformation, and monochorionic twin
      pregnancies at higher risk of adverse outcome.

PMID- 10962046
TI  - Substance abuse in the Republic of Croatia and National Program for Drug Control.
AB  - AIM: To establish the proportions of drug abuse problem in Croatia, with special
      reference to illicit drugs abuse, in order to assess the quality of
      implementation of National Program for Drug Control on the basis of relevant
      indicators. METHODS: Collection and review of data on the extent of particular
      drug abuse among adolescents (aged 13-19), epidemiological data on treated drug
      addicts, and the data from the police and justice. RESULTS: Drug abuse epidemic
      in Croatia started with the beginning of the war in 1991. Tobacco smoking and
      alcohol consumption among adolescents have also become more frequent. In the last
      10 years, the number of illicit drug addicts increased from 1.0 per thousand
      population in 1991 to 2.7 in 1999. The extent of drug use varies within the
      country. The situation is most serious in the coastal area. Data for 1999
      indicate a possible cessation of the epidemic spread, but on the high level of
      incidence (around 1,500 new drug addicts per year, with 85% of heroin addicts).
      CONCLUSION: Although a lot was done due to the initiative of the experts in the
      Government Commission for Suppression of Drug Abuse and the Government Center for
      Prevention and Outpatient Treatment of Addiction, many measures on the National
      Program agenda were not carried out due to the insufficient political support and
      scarcity of mobilized resources. Since the illicit drug abuse is the most serious
      problem among the adolescents today, it must be set high on the list of national
      priorities.

PMID- 10962047
TI  - Basic package of health entitlements and solidarity in the Federation of Bosnia
      and Herzegovina.
AB  - The aim of this report is to provide an overview of the methodology for designing
      a basic package of health entitlements and solidarity in the Federation of Bosnia
      and Herzegovina which will, respecting the principles of solidarity and equity,
      guarantee equal rights to all citizens of the Federation. After the analysis of
      the situation, we specified the reasons for the reform, listed the objectives,
      and described the basis of the basic package design, the establishment of federal
      solidarity, and the plan of realization. We discussed the background ethical
      theories of our policy choice, explicitly stated the normative and technical
      criteria for priority setting, and deliberated Federal financing solidarity
      policy and allocation methodology, as well as criteria for "risk equalization"
      among cantons.

PMID- 10962048
TI  - Muscle fiber type composition and morphometric properties of denervated rat
      extensor digitorum longus muscle.
AB  - AIM: Analysis of fiber type composition and fiber size of extensor digitorum
      longus (EDL) muscle in rats during 30 days of denervation. METHODS: Fiber types
      were defined immunohistochemically using monoclonal antibodies specific for slow
      (type I) and fast fibers (type IIA, IIX, and IIB). Antibodies were applied on
      transverse sections of denervated extensor digitorum longus muscles 6, 12, and 30
      days after denervation. Cross sectional area of muscle fibers was analyzed
      morphometrically by computerized image analysis. RESULTS: Control EDL muscle was
      composed of 41% of type IIB, 32% of IIA, 23% of IIX, and 4% of type I muscle
      fibers. The most profound effect of denervation was observed 30 days after the
      transection of the sciatic nerve. Denervation decreased the percentage of both
      type IIB and type IIX muscle fibers to 36% and 13% of the control muscle,
      respectively (p?0.001 for both), and increased the percentage of types IIA and
      type I muscle fibers to 42% and 9% of the control, respectively (p<0.001 for
      both). Morphometric analysis revealed progressive atrophy of all fast muscle
      fibers, which started 6 days after denervation (p<0.001). Thirty days after the
      sciatic nerve transection, a strong reduction in fiber size of type IIA, IIX, and
      IIB muscle fibers was observed (p<0.001 for each type). Type I muscle fibers
      initially showed the reduction in fiber size (p<0.001) but regained the size of
      control fibers until day 30. CONCLUSION: Denervation decreased the percentage of
      type IIX and IIB muscle fibers, with concomitant increase in type IIA and type I
      muscle fibers. The reduction in fiber size was observed in type IIA, IIX, and IIB
      muscle fibers.

PMID- 10962049
TI  - Distribution of alleles at DQCAR microsatellite locus in the Croatian population.
AB  - AIM: To investigate the polymorphism of DQCAR alleles and their association with
      HLA-DRB1, -DQA1, -DQB1 haplotypic associations in the Croatian population.
      METHODS: Blood samples were collected from 135 healthy unrelated donors from
      Zagreb area previously typed for HLA class II alleles (DRB1, DQA1, DQB1). The
      DQCAR samples were run on a standard denaturing sequencing gel in a DNA sequencer
      and the sequences were analyzed and compared. RESULTS: Among 10 different DQCAR
      alleles found in the population of Croatia, the most frequent were DQCAR 103 bp
      (41.5%), 121 bp (13.7%), 111 bp (11.9%), and 99 bp (10.7%). DQCAR alleles 101 bp,
      115 bp, 123 bp, and 125 bp were not observed. Comparison of DQCAR allele
      frequencies between Croatians and other populations did not reveal any
      significant difference. The study proved a little diversity in DQ1 haplotypic
      associations. Among 141 examined DQ1 associations, 120 were DQCAR 103 bp, whereas
      the remaining 21 were DQCAR 107 bp. The DRB1*07 haplotypic association showed the
      highest diversity of DQCAR alleles (111 bp, 113 bp, 117 bp, 119 bp, and 121 bp).
      Three unusual haplotypic combinations were found: HLA-DRB1*0401, -DQA1*0301, 
      DQB1*0302, -DQCAR119bp; HLA-DRB1*0408, -DQA1*0301, -DQB1*0304, -DQCAR117bp; and
      HLA-DRB1*0701, -DQA1*0201, -DQB1*02, -DQCAR 105bp. CONCLUSION: Specific DQCAR
      alleles observed in association with common Caucasoid haplotypes are also found
      in the Croatian population, but in new and unusual associations. These
      associations have not been reported in other populations, which suggests that
      they might be a characteristic of Croatians.

PMID- 10962050
TI  - Early cardiac rupture following streptokinase in patients with acute myocardial
      infarction: retrospective cohort study.
AB  - AIM: To assess the incidence and timing of cardiac rupture following
      streptokinase (SK) administration in acute myocardial infarction (AMI). METHODS:
      We analyzed retrospectively the clinical sheets of AMI patients treated at the
      Coronary Care Unit in University Hospital Split, Croatia, between January 1,
      1996, and December 31, 1998. We selected the patients who died after SK
      administration (1.5 million U in a 30 min iv. infusion), with a discharge
      diagnosis of "AMI" and "cardiac tamponade - ventricular rupture". AMI was defined
      by typical chest pain, ECG, and/or enzymatic changes. Echo or autopsy verified
      diagnosis of cardiac tamponade and/or rupture, as well as pericardial effusion
      and/or free-wall rupture. RESULTS: Out of 726 AMI patients, 136 (18.7%) were
      treated with SK, and 6 had cardiac rupture (4 men and 2 women; 4.4%). Autopsy
      revealed that 1 patient had ischemic and 2 had transmural hemorrhagic AMI. Three
      out of 6 patients died 2-4, and 3 died 5-7 hours after SK administration. Six
      patients who died from cardiac rupture (mean age 72.3+/-9.0) were significantly
      older than AMI survivors treated with SK (121 patients, mean age 60.5+/-12.0
      years, p<0.001). CONCLUSION: In case of unexplained clinical deterioration in AMI
      patients over 70 during the first hours after SK administration, cardiac
      tamponade due to a free-wall rupture should be suspected. SK administration in
      patients with AMI over 70 years should be a selective and not a routine
      treatment.

PMID- 10962051
TI  - Neurophysiology and molecular genetics of Charcot-Marie-Tooth type 1 neuropathy
      in Croatian children: follow-up study.
AB  - AIM: Longitudinal assessment of clinical and neurophysiological abnormalities in
      childhood and adolescence and incidence analysis of tandem Charcot-Marie-Tooth
      disease type 1A gene duplication in Croatian children with Charcot-Marie-Tooth
      type 1 neuropathy. METHODS: Eight Croatian children with Charcot-Marie-Tooth type
      1 neuropathy, aged 4-19 years, were studied clinically, neurophysiologically, and
      neuropathologically during 1-11 years of follow-up. All children were examined at
      least once, and in 4 children the measurements were repeated. Molecular genetic
      analysis was performed in all patients and their family members in order to
      determine the presence of the Charcot-Marie-Tooth disease type 1A duplication on
      chromosome 17p11.2-p12, using restriction fragment length polymorphic and short
      tandem repeat markers. RESULTS: Clubfoot was the most frequently observed
      clinical feature in children under 10 years of age, whereas muscle hypotrophy,
      scoliosis, and contractures developed in the second decade of life. All patients
      showed decreased motor nerve conduction velocity (7-30 m/s) and prolonged distal
      motor latencies on the first and follow-up examinations. Compound muscle action
      potential amplitude reduction (0.1-1.25 mV) was recorded in the first and second
      decade of life. In 6 out of 8 children, molecular genetic studies demonstrated
      the presence of the 1.5 megabase tandem Charcot-Marie-Tooth disease type 1A
      duplication in 17p11.2-p12, mostly of paternal origin. CONCLUSION: Pronounced
      neurographic abnormalities and mild clinical features characterize Charcot-Marie
      Tooth type 1 neuropathy in the first decade. There were no significant
      differences in neurographic abnormalities in the first or second decade of life
      between Croatian children with and without Charcot-Marie-Tooth type 1A
      duplication.

PMID- 10962053
TI  - Can police car colored flash light induce encephalographic discharges and
      seizures?
AB  - AIM: To explore the epileptogenic potential of a newly introduced police car
      flash light device (930 Heliobe Lightbar). METHODS: A 930 Heliobe Lightbar was
      installed in the EEG laboratory. Thirty patients with known epilepsy, 30
      otherwise healthy subjects with chronic headache, and 15 healthy volunteers were
      examined. All the subjects signed an informed consent and underwent an EEG during
      which photostimulation was performed first with the standard stroboscope, and
      later with the Police lightbar. RESULTS: In all 75 examinees the lightbar did not
      induce clinical or electrographic seizures. In a single patient with epilepsy,
      the lightbar enhanced epileptiform activity induced by standard photic
      stimulation. CONCLUSION: The new Police light bar was found to be non
      epileptogenic.

PMID- 10962052
TI  - Metronidazole in the treatment of chronic radiation proctitis: clinical trial.
AB  - AIM: To evaluate the effectiveness of metronidazole in combination with
      corticosteroids in enema and mesalazine (5-aminosalicylic acid) in comparison
      with the same protocol without metronidazole in the treatment of chronic
      radiation proctitis. METHODS: Sixty patients with rectal bleeding and diarrhea
      were randomly divided into two groups. Patients in the first group were treated
      with metronidazole (3x400 mg orally per day), mesalazine (3x1 g orally per day),
      and betamethasone enema (once a day during 4 weeks). Patients in the second group
      were treated with mesalazine and betamethasone enema, but without metronidazole.
      The efficacy of metronidazole was assessed on the basis of rectal bleeding,
      diarrhea, and rectosigmoidoscopy findings in all patients. RESULTS: The incidence
      of rectal bleeding and mucosal ulcers was significantly lower in the
      metronidazole group, 4 weeks (p=0.009), 3 months (p=0.031), and 12 months
      (p=0.029) after therapy. There was also a significant decrease in diarrhea and
      edema in the metronidazole group, 4 weeks (p=0.044), 3 months (p=0.045), and 12
      months (p=0.034) after treatment. CONCLUSION: Metronidazole in combination with
      mesalazine and betamethasone enemas successfully treats rectal bleeding and
      diarrhea in chronic radiation proctitis.

PMID- 10962054
TI  - Non-fatal occupational injuries requiring admission to hospitals in Al-Khobar
      City, Saudi Arabia: prospective cohort study.
AB  - AIM: To determine the incidence rate of non-fatal occupational injuries among the
      workers insured by the General Organization of Social Insurance requiring
      admission to private hospitals in Al-Khobar city during 1995. METHODS: This
      cohort study was conducted on 65,915 insured industry workers admitted to 2
      randomly selected private hospitals in Al-Khobar City. At admission to hospital,
      a data sheet was filled out with necessary data collected directly from the
      patient and his medical file. RESULTS: The injury incidence rate was 7.1 per
      1,000 full-time workers a year. Nationality-wise, 1. 5% were Saudis, 13.2% were
      Filipinos, and 74.8% were from the Indian subcontinent. Hands and fingers were
      most often injured (32.1%) and fall was the main cause of injury (33.4%). The
      majority of admissions (77.8%) lasted for less than a week. Absence from work was
      longer than 3 weeks in 35.5%, and shorter than 1 week in 24.9% of admissions.
      Majority of the injured workers (65.0%) visited the clinic 2-7 times. Direct
      medical cost per admission was less than US$533 (SR2,000) in 63.9% of the cases
      in one of the hospitals. CONCLUSIONS: The incidence rate of work injuries in
      Saudi Arabian workers was comparable to the rates from other countries. As these
      injuries cause high medical charges, human suffering, and loss of productivity,
      it seems that the social insurance organization should take measures to improve
      the current situation and encourage similar studies to be conducted in this
      field, particularly on severe injuries.

PMID- 10962055
TI  - Help-seeking behavior and self-medication of a population in an urban area in
      Turkey: cross sectional study.
AB  - AIM: To define help-seeking behavior and self-medication among people with
      different symptoms and complaints in an industrialized urban area of Turkey.
      METHODS: This cross-sectional study was carried out in the city center of Kocaeli
      province, Western Turkey, in October-November 1998. To research help-seeking
      behavior in respect of secondary prevention and curative practices, we randomly
      selected households (N=812), interviewed the household members at their home, and
      recorded the reasons for visiting a pharmacy in 6 pharmacies (N=1,331 visits to
      pharmacy) in the Kocaeli region. RESULTS: The majority of interviewed people knew
      the meaning and importance of regular medical checkups, and only 7% had never
      underwent periodic checkups, mainly because of the lack of interest or time. Self
      medication was found to be the dominant mode of help-seeking behavior, especially
      in the case of pain. The proportion of unprescribed to prescribed drugs was
      1:1.75, with analgetics, antipyretics, expectorants, and antitussives as the most
      commonly requested unprescribed drugs. CONCLUSION: A considerable amount of
      health care occured within the popular sector, with self-medication and
      pharmacist's advice as dominant modes of behavior. The health care system should
      take this into account when planning activities aimed at detection of disease.

PMID- 10962056
TI  - Patch reconstruction of hemidiaphragm agenesis by the polypropylene mesh
      prosthesis.
AB  - We present a case of a middle-aged woman with right hemidiaphragm agenesis, which
      became evident after a blunt injury. Ultrasound, X-ray, and computed tomography
      confirmed the diagnosis, and the diaphragmatic congenital defect was closed by
      insertion of a polypropylene mesh prosthesis.

PMID- 10962057
TI  - Osteochondroma in a skeleton from an 11th century Croatian cemetery.
AB  - We present a case of a well-preserved bone tumor in a skeleton from a Croatian
      skeletal series dated to the 11th century AD. The tumor is located on the
      anterior side of the neck of the right femur. The gross morphology of the tumor -
      a round, lumpy, cauliflower-like appearance with a fairly smooth external surface
      - is consistent with osteochondroma. The diagnosis is supported by x-ray and CAT
      scan findings, which show thickened trabeculae and an internal structure of
      cancellous bone interspersed with areas of dense compact bone. Comparison with x
      rays from a patient surgically treated in 1999 for an osteochondroma with the
      same localization shows that the characteristics of the tumor have remained
      unchanged from the 11th century.

PMID- 10962059
TI  - At EASE with ease, or vice versa

PMID- 10962058
TI  - The field hospital.

PMID- 10962060
TI  - Rural aging - a global challenge.

PMID- 10962061
TI  - Spatial differences and seasonal changes of net carbonate accumulation on some
      coral reefs of the Ryukyu Islands, Japan.
AB  - This study sought to understand short-term spatial changes in accretion and
      erosion on (experimental) carbonate blocks on three coral reefs of the Ryukyu
      Islands, Japan. The principal objectives were to differentiate net
      accretion/erosion according to season, location, depth and substrate-type. At all
      locations the summer season showed more positive net weight changes and higher
      coralline algal coverage than the winter season. Windward reefs revealed higher
      net accretion and higher coralline algal coverage than leeward reefs. Massive
      (Holocene) Porites blocks showed highest net loss, followed by Pleistocene
      carbonate and (Holocene) Acropora blocks. High population densities of
      Echinometra mathaei (de Blainville) were recorded on reefs adjacent to large
      human populations and overall net carbonate loss significantly correlated to
      densities of E. mathaei type A.

PMID- 10962062
TI  - Settlement in different-sized patches by the gregarious intertidal barnacle
      Chamaesipho tasmanica Foster and Anderson in New South Wales.
AB  - Most models on settlement of open marine invertebrate populations are based on
      space-limitation. These models, however, do not recognise that free space may not
      drive the demography of populations when larval numbers are small or when larval
      supply varies along a gradient in the habitat. They also do not incorporate the
      effects of larval choice when settling. It has been hypothesised that, in
      gregarious barnacles, the effects of adult conspecifics, rather than available
      free space, may play a primary role in settlement. That is, cues from adults
      along perimeters of patches, rather than space available, may enhance
      colonisation. This study therefore aimed to distinguish between these separate
      influences on populations of Chamaesipho tasmanica, a gregarious barnacle
      characterised by relatively few larvae arriving to settle each year. Patches of
      6, 3 and 1.5 cm diameter were cleared within aggregations of barnacles at three
      heights (Low, Mid, Upper) of Chamaesipho's distribution at two sites and during 2
      years of settlement. Total numbers of settlers in each year were manipulated to
      determine the separate influences on settlement due to availability of substratum
      or the effects of conspecific adults. To test for the effects of available free
      space, numbers of settlers per unit area were analysed. To test for gregarious
      effects due to the presence of adults, numbers of settlers per unit perimeter
      were analysed. While available substratum was found not to affect settlement of
      this barnacle, gregarious settlement in response to adults at perimeters of
      patches was thought to be confounded by differential larval supply and
      differential conspecific cues among heights on the shore. Results from this study
      therefore have important implications for survival of gregarious populations
      following disturbances, especially in species where larval supply is poor.

PMID- 10962063
TI  - Chemical ecology of the Antarctic nudibranch Bathydoris hodgsoni Eliot, 1907:
      defensive role and origin of its natural products.
AB  - A variety of Antarctic marine invertebrates contains secondary metabolites that
      may provide defense against potential predators. However, only in a few cases
      have tissues, extracts or isolated compounds of these invertebrates been tested
      against sympatric predators. The Antarctic nudibranch Bathydoris hodgsoni Eliot,
      1907 contains hodgsonal, a compound only present in the external body (mantle
      tissues), which may protect the slugs from predators. To test this defensive
      hypothesis for hodgsonal, we carried out a series of experiments using the
      sympatric omnivorous seastar Odontaster validus Koehler, 1906 as a potential
      predator. Our experiments revealed that natural concentrations of hodgsonal
      elicit significant feeding deterrent responses in O. validus. Furthermore,
      hodgsonal is probably biosynthesized de novo by the nudibranch, since it was not
      detected in the viscera (as it should be in the case of a dietary compound), its
      concentration in the mantle (0.05-0.15% dry mass) is quite constant in
      individuals from different localities and depths, and its sequestration from a
      particular dietary source is unlikely because B. hodgsoni is an omnivorous
      feeder.

PMID- 10962064
TI  - Burrowing in the Antarctic anemone, Halcampoides sp., from Signy Island,
      Antarctica.
AB  - Antarctic anemones of the genus Halcampoides inhabit low intertidal and shallow
      subtidal zones. They readily burrow into soft sediments following disturbance.
      The process of re-burying was recorded using time-lapse video in the aquarium of
      the British Antarctic Survey with specimens of a species collected from the
      shallow sublittoral (<1 m depth) at Signy Island. Penetration of the sediment
      takes place by a similar mechanism to that employed by burrowing anemones such as
      Peachia hastata from lower latitudes. Penetration initially is brought about by
      peristaltic contractions that involve only the modified base, or physa. Later, as
      the column becomes buried, the peristaltic contractions start in the upper part
      of the scapus and pass down the column before extending the physa. At this stage
      penetration is aided by contractions of the longitudinal muscles that draw the
      column down into the sediment. At 0 degrees C the frequency of initiation of
      peristaltic contractions down the column, and of contractions of the longitudinal
      muscles are on average >1.6 and >4.0 times slower, respectively, compared with
      those of Peachia hastata from Scotland, recorded at approximately 11-14 degrees
      C. Q(10) values calculated from these data are in the range 1.4-3.0, and thus
      provide little evidence supporting any evolutionary acclimation of the processes
      involved in burrowing has occurred in Halcampoides from the Antarctic, although
      the data are limited.

PMID- 10962065
TI  - Experimental study of suspension-feeding activity in the serpulid polychaete
      Ditrupa arietina (O.F. Muller).
AB  - As time spent feeding can be an index of the feeding intensity, we attempted to
      describe the filtering activity in the suspension-feeding polychaete Ditrupa
      arietina. This description was based on the detection of the opening of the gill
      crown by an automated image analysis system. The common pattern of activity could
      be described as the succession of filtering events and resting periods of which
      the number and the mean duration differed greatly from one worm to another.
      Filtering activity in D. arietina was neither a continuous process nor even a
      process having a particular rhythm. Within a same batch of worms, total
      filtration durations could represent between 12.5 and 87.5% of the total
      experimental time. Despite a strong inter-individual variability, our results
      showed the existence of pronounced seasonal variations in the activity of the
      gill-crown. In May, worms spent less than 25% of time feeding compared to more
      than 50% during the rest of year. These temporal changes appeared to result from
      the physiological state of the worms (reproductive period and ageing) at the time
      of the experiment.

PMID- 10962066
TI  - Fast repetition rate (FRR) fluorometry: variability of chlorophyll a fluorescence
      yields in colonies of the corals, Montastraea faveolata (w.) and Diploria
      labyrinthiformes (h.) recovering from bleaching.
AB  - Recently, an underwater version of a fast repetition rate fluorometer (FRRF) was
      developed for the non-destructive study of fluorescence yields in benthic
      photoautotrophs. We used an FRRF to study bleached colonies of the corals,
      Montastraea faveolata and Diploria labyrinthiformes at sites surrounding Lee
      Stocking Island, Exuma, Bahamas, to assess their recovery from bleaching (
      approximately 1 year after the initial bleaching event) induced by elevated
      temperatures. The steady state quantum yields of chlorophyll a fluorescence
      (DeltaF'/F'(m)) from photosystem II (PSII) within coral colonies were separated
      into three categories representing visibly distinct degrees of bleaching ranging
      from no bleaching to completely bleached areas. Differences in DeltaF'/F'(m) were
      significantly different from bleached to unbleached regions within colonies.
      Dark, unbleached regions within colonies exhibited significantly higher
      DeltaF'/F'(m) values (0.438+/-0.019; mean+/-S.D.) when compared to lighter
      regions, and occupied a majority of the colonies' surface area (46-73%). Bleached
      regions exhibited significantly lower DeltaF'/F'(m) (0.337+/-0.014) and covered
      only 7-25% of the colonies' surface area. The observations from this study
      suggest that zooxanthellae in bleached regions of a colony exhibit reduced
      photosynthetic activity as long as one year after a bleaching event and that in
      situ fluorescence techniques such as FRRF are an effective means of studying
      coral responses and recovery from natural or anthropogenic stress in a non
      destructive manner.

PMID- 10962067
TI  - Thermal resistance, developmental rate and heat shock proteins in Artemia
      franciscana, from San Francisco Bay and southern Vietnam.
AB  - Cysts (encysted gastrula embryos) of Artemia franciscana collected from salterns
      in San Francisco Bay, California, USA (SF) were inoculated into much warmer
      growth ponds in the Mekong Delta region of Vietnam (V) in 1996. V adults arising
      directly from these cysts during 17 April to 15 May produced their own cysts,
      which were collected, processed and stored until shipped to the USA for study.
      Adults grown in the laboratory from SF cysts (those used for the inoculation)
      were less resistant to high temperature than adults cultured from V cysts. V
      cysts produced heat-resistant adults, even though cultured under the same
      laboratory conditions as SF animals, at much lower temperatures than they ever
      experienced in Vietnam. Differences in thermal performance between SF and V
      adults were retained in the second generation, cultured from cysts produced in
      the laboratory by first generation adults, suggesting a genetic basis for the
      better heat resistance of V adults. We propose that the operation of natural
      selection in the Vietnam growth ponds produced adults with improved thermal
      tolerance, and that the basis for this tolerance was incorporated into the
      developmental program of their cysts. Surprisingly, differences in heat
      resistance of laboratory reared animals were not reflected in constitutive levels
      of the hsp70 family which were similar in first generation SF and V adults. A
      conditioning heat shock (HS, 37 degrees C, 30 min) led to the same level of
      induced thermotolerance in SF and V first generation adults when evaluated 24 h
      post-HS. Levels of hsp70 were also up-regulated at that time, but to about the
      same extent in SF and V adults. Developmental rates of SF cysts used for the
      inoculation were faster than those of cysts produced in Vietnam when both were
      incubated at 21+/-1 degrees C, suggesting that V cysts have become adapted to
      develop at higher temperatures.

PMID- 10962068
TI  - Effect of juvenile hormone and serotonin (5-HT) on mixis induction of the rotifer
      Brachionus plicatilis Muller.
AB  - Juvenile hormone (JH) and serotonin (5-HT) were previously shown to enhance
      mictic (sexual) female production of the rotifer Brachionus plicatilis in batch
      cultures. To explore the basis of these effects, experiments were conducted on
      isolated individuals. JH treatment of maternal rotifers with 5 and 50 ugml(-1)
      (18.8 and 187.7 uM) resulted in significantly higher (P<0.05) mictic female
      production in the second (F(2)) and third (F(3)) generations. JH treatment was
      effective even at a lower food concentration of 7x10(5) cellsml(-1), but it was
      not effective when free ammonia was added at 2.4 and 3.1 ugml(-1). Mictic female
      production was not increased with exposure to 5-HT up to 50 ugml(-1) (129.1 uM)
      concentrations. When food level was reduced to 7x10(5) cellsml(-1), however, 5-HT
      treated rotifers produced significantly (P<0.05) more mictic females than the
      control, particularly in F(3) generation. Mictic female production of 5-HT
      treated rotifers did not differ from that of the control with or without free
      ammonia, but the intrinsic rate of natural increase (r) of 5-HT-treated rotifers
      at 3.1 ugml(-1) free ammonia was significantly higher than the control. These
      results show that juvenile hormone increases mictic female production under
      optimum and sub-optimum food levels, whereas 5-HT increases both mictic female
      production at low food level and population growth rate at high free ammonia
      concentrations. These compounds could be used to manage rotifer cultures and
      probe the mechanisms controlling the rotifer life cycle as it switches to mictic
      reproduction.

PMID- 10962069
TI  - Consistent spatial patterns of arrival of larvae of the honeycomb barnacle
      Chamaesipho tasmanica Foster and Anderson in New South Wales.
AB  - The small honeycomb barnacle Chamaesipho tasmanica occurs in patches at high
      levels on exposed rocky shores, but often carpets the substratum at mid-shore
      levels of sheltered shores in south-eastern Australia. Studies of larval supply
      from 1990 to 1993 and concurrent monitoring of settlement from 1991 to 1993
      revealed that larval arrival and settlement were typified by trickles of larvae
      from late July to December (although some were observed in January and February).
      Major pulses of arriving cyprids were also recorded once or twice each year.
      While local patterns of water-flow had no impact on numbers of larvae arriving,
      major peaks of larval arrival were always associated with strong southerly winds
      during new and full moons. There was a consistent spatial pattern of larval
      supply; more larvae were always caught in one area low on the shore. Numbers of
      larvae caught were, however, very sporadic within a given year and very variable
      from one year to the next. While the different numbers of cyprids in different
      places cannot be explained by cyprids arriving first on lower parts of the shore,
      longer periods of submersion nor aggregations of larvae in the plankton,
      recurrent patterns of arrival of larvae suggest that local site-specific
      characteristics have an influence on the demography of populations of this
      species. Variations in numbers of larvae arriving were responsible for the
      variations in distributions of juveniles on the substratum.

PMID- 10962070
TI  - The effect of extrinsic and intrinsic factors on oxygen consumption by the
      southern rock lobster, Jasus edwardsii.
AB  - The oxygen consumption rate of the southern rock lobster, Jasus edwardsii, was
      evaluated in response to body weight, temperature, activity, handling, diurnal
      rhythm, feeding and oxygen saturation level. There was a positive relationship
      between standard oxygen consumption (M(O(2))) and both body weight and water
      temperature. The relationship between total oxygen consumption and wet whole body
      weight was described by the equation: LogM(O(2))=0.595log W-0.396 (r(2)=0.83).
      The relationship between weight-specific oxygen consumption and temperature was
      described by the equation: LogM(O(2))=0.047T-2.25 (r(2)=0.94). Activity had a
      significant influence on the oxygen consumption rate, causing a three-fold
      increase above the standard rate at the temperature of acclimation (13 degrees
      C). However, at temperatures approaching the upper and lower extremes, lobsters
      had a decreased ability to increase their oxygen consumption rates during
      activity. Lobsters took 4.5-5 h to return to standard oxygen consumption rates
      after a period of emersion and handling. A strong diurnal rhythm to oxygen
      consumption was recorded. J. edwardsii displayed a classic postprandial increase
      in oxygen consumption. A peak (1.72 times standard M(O(2))) occurred 10-13 h
      after feeding with an increase above standard M(O(2)) being maintained for 42 h.
      In its rested state J. edwardsii was an oxygen regulator down to a critical
      oxygen tension of 58 Torr, whilst activity resulted in the critical oxygen
      tension increasing to 93 Torr.

PMID- 10962072
TI  - Executive summary

PMID- 10962071
TI  - Protection of the public in situations of prolonged radiation exposure. The
      application of the Commission's system of radiological protection to controllable
      radiation exposure due to natural sources and long-lived radioactive residues.
AB  - This report provides guidance on the application of the ICRP system of
      radiological protection to prolonged exposure situations affecting members of the
      public. It addresses the general application of the Commission's system to the
      control of prolonged exposures resulting from practices and to the undertaking of
      interventions in prolonged exposure situations. Additionally, it provides
      recommendations on generic reference levels for such interventions. The report
      also considers some specific situations and discusses a number of issues that
      have been of concern, namely: natural radiation sources that may give rise to
      high doses; the restoration and rehabilitation of sites where human activities
      involving radioactive substances have been carried out; the return to 'normality'
      following an accident that has released radioactive substances to the
      environment; and the global marketing of commodities for public consumption that
      contain radioactive substances. Annexes provide some examples of prolonged
      exposure situations and discuss the radiological protection quantities, radiation
      induced health effects and aspects of the Commission's system of radiological
      protection relevant to prolonged exposure. Quantitative recommendations for
      prolonged exposures are provided in the report. They must be interpreted with
      extreme caution; Chapters 4 and 5 stress the upper bound nature of the following
      values: Generic reference levels for intervention, in terms of existing total
      annual doses, are given as < approximately 100 mSv, above which intervention is
      almost always justifiable (situations for which the annual dose threshold for
      deterministic effects in relevant organs is exceeded will almost always require
      intervention), and < approximately 10 mSv, below which intervention is not likely
      to be justifiable (and above which it may be necessary). Intervention exemption
      levels for commodities, especially building materials, are expressed as an
      additional annual dose of approximately 1 mSv. The dose limit for exposures of
      the public from practices is expressed as aggregated (prolonged and transitory)
      additional annual doses from all relevant practices of 1 mSv. Dose constraints
      for sources within practices are expressed as an additional annual dose lower
      than 1 mSv (e.g. of approximately 0.3 mSv), which could be approximately 0.1 mSv
      for the prolonged exposure component. An exemption level for practices is
      expressed as an additional annual dose of approximately 0.01 mSv.

PMID- 10962074
TI  - Application of the system of radiological protection to practices resulting in
      prolonged exposure

PMID- 10962075
TI  - Application of the system of radiological protection to intervention in prolonged
      exposure situations

PMID- 10962076
TI  - Generic reference levels of existing annual dose for intervention in prolonged
      exposure situations

PMID- 10962077
TI  - Application of the recommendations to specific prolonged exposure situations

PMID- 10962078
TI  - Outlook

PMID- 10962080
TI  - B. Annex B: radiological protection quantities in the context of prolonged
      exposures

PMID- 10962079
TI  - A. Annex A: some prolonged exposure situations

PMID- 10962082
TI  - D. Annex D: the system of protection in the context of prolonged exposure

PMID- 10962081
TI  - C. Annex C: radiation health effects in the context of prolonged exposure

PMID- 10962083
TI  - References

PMID- 10962084
TI  - Together, we can make it!

PMID- 10962085
TI  - Preface

PMID- 10962086
TI  - Understanding the fluorescence changes of human plasminogen when it binds the
      ligand, 6-aminohexanoate: a synthesis.
AB  - This work attempts to explain several aspects of the response of plasminogen to 6
      aminohexanoate (6-AH). These responses include the overall fluorescent changes
      that occur when plasminogen binds the ligand, the changes shown by the individual
      domains when they bind the ligand, and the changes in structure shown by the
      holoprotein when it binds 6-AH. The results have implications for understanding
      the physicochemical behavior of all kringle based proteins.

PMID- 10962087
TI  - The citrate ion increases the conformational stability of alpha(1)-antitrypsin.
AB  - Sodium citrate has previously been shown to convert native alpha(1)-antitrypsin
      into the inactive latent state and cause alpha(1)-antitrypsin to polymerize via
      the C-sheet pathway instead of the more common A-sheet pathway. In order to begin
      to understand these dramatic effects, we have examined the influence of low
      concentrations of sodium citrate upon the structure, stability and function of
      alpha(1)-antitrypsin. In 0.5 M citrate, the midpoint of guanidine hydrochloride
      induced unfolding was increased by 1.8 M and the rate of heat inactivation was
      decreased approximately 30-fold compared with Tris or phosphate buffer. alpha(1)
      Antitrypsin was fully active in the presence of a range of citrate concentrations
      (0. 1-0.5 M), forming a stable 1:1 complex with chymotrypsin. The association
      rate constant between alpha(1)-antitrypsin and chymotrypsin was decreased with
      increasing citrate concentration. Fluorescence and circular dichroism
      spectroscopy demonstrated no significant changes in the tertiary structure due to
      the presence of citrate. However, the insertion rate of exogenous reactive-center
      loop peptide increased with increasing citrate concentration, indicating some
      structural changes in the A beta-sheet region. Taken together, these data suggest
      that in the presence of 0.5 M citrate alpha(1)-antitrypsin adopts a highly stable
      but active conformation.

PMID- 10962089
TI  - Development of laminin receptor agonists: identification of important functional
      residues by alanine scanning.
AB  - An antagonist of cellular adhesion and motility, acetyl-C-[S-Acm]-VIGYSGDRC-[S
      Acm]-NH(2) (mEGF(33-42)), shares homology with the agonist sequence CDPGYIGSR
      NH(2). It has been proposed that the latter peptide binds to the high affinity 67
      kDa laminin receptor. Both peptides have equal affinities for the receptor and
      similar conformations have been derived for both. We have examined the importance
      of individual non-homologous residues with respect to receptor binding and
      antagonistic properties of mEGF(33-42). Alanine scanning of non-conserved
      residues in the N-terminal half of mEGF(33-42) caused loss of biological activity
      with respect to cell attachment, receptor binding and migratory response.
      Substitution of alanine for serine (position 6) caused loss of laminin-specific
      cell attachment and receptor binding activities. However, the peptide did
      stimulate migration suggesting that this peptide may be a non-specific stimulator
      of migration. In contrast, alanine substitution for the C-terminal Cys-S-Acm had
      no apparent effect on the attachment or receptor binding activities of the
      peptide but generated an agonist from the antagonist parent. Comparison of the
      modelled folds of the alanine containing peptides revealed the presence of
      significant helical content in those peptides capable of stimulating migration
      and suggests that a reduction in bulk in the N-terminal residues is not conducive
      to adopting a productive binding conformation.

PMID- 10962090
TI  - Conformational change of dihydrofolate reductase near the active site after thiol
      modification: detected by limited proteolysis.
AB  - Kinetic studies of chicken liver dihydrofolate reductase (CL-DHFR) and Chinese
      hamster ovary DHFR (CH-DHFR) activated following p-hydroxymercuribenzoate (p-HMB)
      modification indicate a conformational change at the active site, suggesting a
      loosening of the enzyme structure upon SH modification. In the present study,
      limited proteolysis was applied to detect the subtle conformational changes in SH
      modified DHFRs. The digested peptide fragments were separated by Tricine SDS-PAGE
      and sequenced by Edman auto-degradation. The thiol modifier N-iodoacetyl-N'-(5
      sulfo-1-nophthyl) ethylenediamine (IAEANS), which activates these DHFRs only
      weakly, was used as a control. The results of sequencing showed that compared to
      native enzyme, there is one additional cleavage site near the active site in p
      HMB-modified CL-DHFR, two additional sites in p-HMB-modified CH-DHFR, but no
      additional site for IAEANS-modified DHFRs. These results indicate that activation
      of DHFRs following thiol modification is accompanied by a conformational change
      at or near the active site. This subtle change in the active site conformation
      results in a pronounced change in enzyme activity. This provides further evidence
      that flexibility at the active site is essential for full expression of enzyme
      catalytic activity. Comparing results obtained from previous experiments on
      guanidine- and urea-activated CL-DHFR, this shows that a conformational change
      near helix(28-39) is sufficient for full activation of DHFR.

PMID- 10962092
TI  - Nucleotide-induced movements in the myosin head near the converter region.
AB  - Structural changes in subfragment 1 of skeletal muscle myosin were investigated
      by cross-linking trypsin-cleaved S1 with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide. In the absence of nucleotide the alkali light
      chains are cross-linked to the 27 kDa heavy chain fragment; the presence of MgATP
      reduces the efficiency of this reaction. On the other hand, MgATP promotes the
      cross-link formation between the N-terminal 27 kDa and C-terminal 20 kDa
      fragments of the heavy chain. The chemical cleavage of the cross-linked heavy
      chains fragments with N-chlorosuccinimide and hydroxylamine indicates that the
      cross-links are formed between the regions spanning residues 131-204 and 699-809.
      These results indicate that the two regions of the heavy chain that are
      relatively distant in nucleotide-free skeletal S1 [Rayment et al. (1993) Science
      261, 50-58] can potentially interact upon addition of nucleotide.

PMID- 10962093
TI  - Two transport binding sites of P-glycoprotein are unequal yet contingent: initial
      rate kinetic analysis by ATP hydrolysis demonstrates intersite dependence.
AB  - The ATP-dependent transport enzyme known as P-glycoprotein (P-gp) confers
      multidrug resistance (MDR) against many unrelated drugs and xenobiotics. To
      understand better the broad substrate specificity of the enzyme as well as the
      mechanism of substrate transport out of the cell, it is critical to characterize
      the substrate binding sites. Since approximately 1 ATP is hydrolyzed per
      transport event, phosphate release rate provides a steady-state kinetics assay.
      Notably, the substrate H33342 causes a decrease in the baseline hydrolysis of ATP
      (probably due to competition for transport with an endogenous membrane lipid
      substrate) providing an excellent tool for a comprehensive graphical kinetic
      analysis of the interaction of substrate pairs at the transport site(s) allowing
      the determination of inhibition type and hence characterization of transport
      binding sites. The substrate H33342 interacted with quinidine, progesterone, and
      propranolol in a non-competitive manner, indicating that binding of H33342
      precludes active transport of these other substrates at a distinct site.
      Compounds such as TPP+ and verapamil, and perhaps also nicardipine, interacted
      with H33342 as mixed-type inhibitors. This type of interaction results from a
      reduced affinity at the opposing active site by a factor of alpha and sometimes a
      partial activity of a fraction beta. Indeed, H33342 binding caused a roughly four
      fold reduced affinity for TPP+. Using this definitive approach to inhibition
      kinetics, we were able to establish traits of a second transport site in P-gp.
      Therefore, the sites are unequal; however, the performance at one site is
      contingent on the other being unoccupied, and transport is also sometimes
      mitigated when the other site is occupied.

PMID- 10962094
TI  - The preparation and catalytic properties of recombinant human prostate-specific
      antigen (rPSA).
AB  - The serine proteinase prostate-specific antigen (PSA), and its complex with the
      serine proteinase inhibitor alpha(1)-antichymotrypsin (ACT), have been used as
      markers for the diagnosis of prostate cancer. PSA prepared from seminal fluid is
      typically contaminated with the trypsin-like glandular kallikrein (hK2). Here we
      describe a convenient and reproducible preparation of catalytically active
      recombinant PSA (rPSA) and demonstrate an overall similarity in the properties of
      cloned and refolded rPSA to PSA purified from seminal fluid. We also present
      results that are relevant for increasing the sensitivity of assays of PSA
      activity in biological fluids, for the putative role of PSA activity in
      physiologically important processes, including prostate cancer metastasis, and
      for the design of PSA inhibitors. Specifically, we find that added salts, in
      particular NaCl, give rise to dramatic increases in rPSA catalytic activity, as
      does added glycerol. On the other hand, Zn(2+), spermine, and spermidine, each a
      major component of seminal and prostatic fluid, strongly inhibit rPSA activity,
      with Zn(2+) being a non-competitive inhibitor while spermine is a competitive
      inhibitor. Citrate, also a major component of seminal and prostatic fluid,
      spermine, and spermidine each protect rPSA from Zn(2+) inhibition, presumably via
      Zn(2+) sequestration. Finally, rPSA efficiently proteolyzes several protein
      substrates.

PMID- 10962103
TI  - Nitric oxide protects nitric oxide synthase function from hydroxyl radical
      induced inhibition.
AB  - The interdependent relationships among nitric oxide synthase (NOS), its coenzyme,
      cofactors and nitric oxide (NO(free radical) were studied using electron
      paramagnetic resonance spectroscopy. It was found that superoxide-dependent
      hydroxyl free radical (OH(free radical), derived from NOS coenzyme and cofactors,
      inhibits NOS activity, and that endogenous NO(free radical) generated by NOS
      scavenges OH(free radical) and protects NOS function. These results reveal a new
      role for NO(free radical) that may be important in NOS function and cellular free
      radical homeostasis.

PMID- 10962104
TI  - Expression and purification of a recombinant DNA-binding domain of ADR6 protein
      from Escherichia coli and its secondary structure characterization.
AB  - From Saccharomyces cerevisiae, a piece of ADR6 gene that encodes a DNA-binding
      domain of ADR6 protein was cloned and expressed in Escherichia coli. With Ni
      chelating column and high-performance liquid chromatography (HPLC), This
      recombinant protein (RDB-ADR6) could reach more than 95% purity. The molecular
      weight (MW) of RDB-ADR6 is 13405 Da with mass spectra technique containing 114
      amino acid residues. Structural aspects of RDB-ADR6 were examined by
      spectroscopic techniques. It contains approximately 25% alpha-helix and 24% beta
      turn both with circular dichroism (CD) and Fourier transform infrared
      spectroscopy (FTIR). Percent of beta-sheet differs between these two methods in
      that 22% in CD while 35% in FTIR. RDB-ADR6 contains only one tryptophan residue.
      Fluorescence studies show that this residue may lie in a hydrophobic circumstance
      either on or near the surface of the molecule. This was confirmed by a blue shift
      of 20 nm in the fluorescence emission spectrum as compared to the protein in 6 M
      guanidine hydrochloride (GuHCl) and by quenching studies with KI. Effects of
      different pH and SDS in different concentration on the secondary structure of RDB
      ADR6 were also studied. A model was obtained by comparative modeling with
      homologous known structure protein by program Modeller 4.

PMID- 10962105
TI  - The small heat-shock chaperone protein, alpha-crystallin, does not recognize
      stable molten globule states of cytosolic proteins.
AB  - The small heat-shock protein (sHsp), alpha-crystallin, acts as a molecular
      chaperone by interacting with destabilized 'substrate' proteins to prevent their
      precipitation from solution under conditions of stress. alpha-Crystallin and all
      sHsps are intracellular proteins. Similarly to other chaperones, the 'substrate'
      protein is in an intermediately folded, partly structured molten globule state
      when it interacts and complexes with alpha-crystallin. In this study, stable
      molten globule states of the cytosolic proteins, gamma-crystallin and myoglobin,
      have been prepared. Within the lens, gamma-crystallin naturally interacts with
      alpha-crystallin and myoglobin and alpha-crystallin are present together in
      muscle tissue. The molten globule states of gamma-crystallin and myoglobin were
      prepared by reacting gamma-crystallin with glucose 6-phosphate and by removing
      the haem group of myoglobin. Following spectroscopic characterisation of these
      modified proteins, their interaction with alpha-crystallin was examined by a
      variety of spectroscopic and protein chemical techniques. In both cases, there
      was no interaction with alpha-crystallin that led to complexation. It is
      concluded that alpha-crystallin does not recognise stable molten globule states
      of cytosolic 'substrate' proteins and only interacts with molten globule states
      of proteins that are on the irreversible pathway towards an aggregated and
      precipitated form.

PMID- 10962106
TI  - Influence of phosphatidylinositol 4,5-bisphosphate on human phospholipase D1 wild
      type and deletion mutants: is there evidence for an interaction of
      phosphatidylinositol 4,5-bisphosphate with the putative pleckstrin homology
      domain?
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is an essential cofactor of
      phospholipase D (PLD) enzymes. In order to further characterize its role in PLD
      activation, we have constructed N-terminal deletion mutants of the human PLD1
      (hPLD1) and a mutant lacking the putative pleckstrin homology domain (delta PH),
      which has been proposed to be involved in PIP(2) binding. For the N-terminal
      deletion mutants (up to 303 amino acids) and the delta PH mutant we found no
      significant differences compared to the hPLD1 wild-type, except changes in the
      specific activities: the K(m) values were about 20 microM for the substrate
      phosphatidylcholine, and PIP(2) activated the PLD enzymes maximally between 5 and
      10 microM. In contrast, preincubation of the PLD proteins with 5-10 microM PIP(2)
      or PIP(2)-containing lipid vesicles inhibited the PLD activity. This inhibition
      was neither abolished by n-octyl-beta-D-glucopyranoside or neomycin nor by the
      ADP-ribosylation factor, another activator of PLD enzymes. All tested PLD
      proteins were active without PIP(2) in the presence of 1 M ammonium sulfate. The
      303 N-terminal amino acids of hPLD1 are not involved in substrate binding or the
      interaction with PIP(2). Our data indicate further that the putative PH domain of
      hPLD1 is not responsible for the essential effects of PIP(2) on PLD activity.

PMID- 10962107
TI  - Aryl-alcohol oxidase protein sequence: a comparison with glucose oxidase and
      other FAD oxidoreductases.
AB  - Aryl-alcohol oxidase (AAO), an FAD-dependent enzyme involved in lignin
      degradation, has been cloned from Pleurotus eryngii. The AAO protein is composed
      of 593 amino acids, 27 of which form a signal peptide. It shows 33% sequence
      identity with glucose oxidase from Aspergillus niger and lower homology with
      other oxidoreductases. The predicted secondary structures of both enzymes are
      very similar. For AAO, it is predicted to contain 13 putative alpha-helices and
      two major beta-sheets, each of the putative beta-sheets formed by six beta
      strands. The ADP binding site and the signature-2 consensus sequence of the
      glucose-methanol-choline (GMC) oxidoreductases were also present. Moreover,
      residues potentially involved in catalysis and substrate binding were identified
      in the vicinity of the flavin ring. They include two histidines (H502 and H546)
      and several aromatic residues (Y78, Y92 and F501), as reported in other FAD
      oxidoreductases.

PMID- 10962108
TI  - Amino acid sequence of VlF: identification in the C-terminal domain of residues
      common to non-hemorrhagic metalloproteinases from snake venoms.
AB  - The complete amino acid sequence of a non-hemorrhagic fibrino(geno)lytic enzyme
      (VlF) isolated from Vipera lebetina venom has been determined. VlF was subjected
      to separate enzymatic and chemical digestions. Resulting fragments were purified
      by RP-HPLC and subjected for sequencing by automated Edman degradation. The amino
      terminus of VlF was determined by mass spectrometry. VlF was shown to be composed
      of 202 residues having a relative molecular mass of 22,826 Da and containing a
      zinc-binding site and a catalytically active residue. It displayed significant
      sequence similarities with many other mature metalloproteinases reported from
      snake venoms. Sequence comparison of hemorrhagic and non-hemorrhagic mature
      metalloproteinases revealed the presence at the C-terminal part of the enzymes of
      two residues common to only hemorrhagic metalloproteinases and two others shared
      by only non-hemorrhagic ones.

PMID- 10962110
TI  - Analysis of T wave changes by activation recovery interval in patients with
      atrial septal defect.
AB  - We examined the distributions of the activation recovery interval (ARI), which is
      correlated with the local action potential duration (APD), to clarify the origin
      of the repolarization changes in ASD. The ECGs, QRST isointegral maps and ARI
      isochronal maps of 21 children with ASD from 3 to 5 years old in age were studied
      in comparison with 21 age-matched normal children. A conventional and 87 unipolar
      body surface ECG were simultaneously recorded. The ARIs were determined from the
      first derivatives of the ECG waveforms. Abnormal ST-T patterns were observed in
      11 of 21 ASD, but only in two normal children. The QRST maps of a split positive
      area pattern were seen in 15 of ASD but none of the normal. In the ARI maps, all
      the normal children exhibited a short-ARI area on the left and a long-ARI area on
      the right side of the chest. In 19 of ASD, the ARI distribution revealed a
      leftward extension of the long-ARI area on the anterior chest, a relative
      shortening on the right anterior chest, and a localized prolonged ARI on the left
      anterior chest. The results suggest that right ventricular (RV) volume overload
      in ASD produces a localized prolongation of the APD on the RV epicardium.

PMID- 10962109
TI  - Prediction of viability by pulsed-wave Doppler tissue sampling of asynergic
      myocardium during low-dose dobutamine challenge.
AB  - Dobutamine stress echocardiography is widely used to predict reversible left
      ventricular dysfunction, but evaluation with this method is subjective. Pulsed
      wave tissue Doppler imaging is a new technique that allows to obtain quantitative
      data on wall motion velocities of different myocardial segments through sample
      volume placement. Therefore, this tool in combination with DSE may be suitable
      for identifying viability in asynergic myocardium. To evaluate this, in 40
      patients (mean age 57+/-9) with resting dyssynergy (akinesis in 52, hypokinesis
      in 30) baseline wall motion scores and tissue Doppler variables were collected
      before and after 5 min infusion of 10 microg/kg per min dobutamine. Forty-six of
      82 segments were classified as viable (a reduction in segmental score of at least
      one grade) according to follow-up echocardiography that was performed 4 weeks
      after revascularization. While myocardial S velocity percent increase in viable
      segments was 45+/-10, the increase was 25+/-12 in necrotic segments (n=36) during
      10 microg dobutamine infusion (P=0.0001). Assuming 35% as a cut-off for viability
      the increase in S velocities by DSE yielded an 89% sensitivity and 86%
      specificity for predicting post-revascularization functional recovery. In
      conclusion, pulsed-wave tissue Doppler imaging of asynergic myocardium during
      dobutamine stress echocardiography can identify the viability quantitatively.

PMID- 10962111
TI  - Residual atrial fibrillation and clinical consequences following postoperative
      supraventricular arrhythmias.
AB  - AIMS: This retrospective study investigated whether the supraventricular
      arrhythmias (SVA) observed during cardiac surgery are limited to or persist
      beyond the postoperative period, their clinical consequences and whether they are
      influenced by preoperative and postoperative factors. METHODS: A total of 375
      patients undergoing elective bypass graft surgery over a 15-month period by three
      surgeons were included. All patients had their preoperative medications continued
      to the day of surgery and prophylactic anti-arrhythmic medications were not used
      in any of the cases. Standard anaesthetic techniques were used. Rhythm
      disturbances were diagnosed by ECG. The arrhythmias were treated medically or by
      cardioversion. All patients were followed up for 6 months. RESULTS: Postoperative
      SVA occurred in 25% of patients. The commonest arrhythmia was atrial fibrillation
      (89.4%), followed by atrial flutter (6.4%) and supraventricular tachycardia
      (4.2%). In 89. 8% of the cases, the arrhythmias occurred within the first four
      postoperative days with a maximum incidence on the second day (27. 7%). Atrial
      fibrillation was still present in 50% of patients at hospital discharge and in
      39% at 6 months follow up. Patients with arrhythmias had a prolonged hospital
      stay (7.7+/-2.6 vs. 6.0+/-2.6 days; P<0.05). There was no hospital mortality in
      the study and the incidence of postoperative stroke was equal in the sinus rhythm
      and arrhythmia patients (1.1%). SVA were more frequent when cardioplegia was used
      to protect the heart (32%) than with intermittent ischaemia (9%; P<0.001). At 6
      months follow up, the patients receiving cardioplegia also had a higher
      prevalence of atrial fibrillation than those operated with intermittent ischaemia
      (41% vs. 22%; P<0. 05). The incidence of SVA and persistence of atrial
      fibrillation was unrelated to other preoperative and intraoperative factors.
      CONCLUSION: Postoperative supraventricular arrhythmias have a long-lasting effect
      on cardiac rhythm: patients with SVA have a high probability of remaining in
      atrial fibrillation at hospital discharge and 6 months after surgery. The
      occurrence of atrial fibrillation seems to be influenced by the type of
      myocardial protection used but this does not appear to exert harmful effects.

PMID- 10962112
TI  - Cardiac autonomic dysfunction in AIDS is not secondary to heart failure.
AB  - OBJECTIVE: Heart rate variability (HRV) is a marker of cardiovascular autonomic
      tone, and is also known to be reduced in association with cardiac dysfunction.
      Abnormal autonomic function tests are common in HIV infected individuals, but the
      contribution of heart disease to such findings is not known. Spectral analysis of
      heart rate variability is a sensitive technique for measurement of cardiovascular
      autonomic function, which also allows differential assessment of parasympathetic
      and sympathetic components. The aim of this study was to characterise the nature
      of autonomic dysfunction in patients with AIDS and to compare our findings with
      those seen in HIV seronegative patients with established heart disease. METHODS:
      HRV was measured prospectively by spectral analysis in 10 subjects with dilated
      cardiomyopathy (age 45.7+/-6.9 years), 10 subjects with AIDS and no clinical
      evidence of heart disease (age 37.9+/-5.4 years), and 10 healthy HIV seronegative
      controls (age 41.7+/-13.9 years). RESULTS: All components of HRV were reduced in
      subjects with cardiomyopathy (P<0.005), and markedly so in subjects with AIDS
      (P<0. 0001) compared with controls. CONCLUSIONS: HIV infection may be associated
      with severe global autonomic dysfunction, which is not related to heart disease.

PMID- 10962113
TI  - Effects of acute hyperglycaemia on cardiac function: an echocardiographic study
      of monozygotic twins.
AB  - BACKGROUND: A major cause of morbidity in type I diabetes is congestive heart
      failure due predominantly to left ventricular diastolic dysfunction. The
      mechanism of diastolic dysfunction remains unknown and does not relate to blood
      pressure, microvascular complications and glycated haemoglobin. Hyperglycaemia is
      the hallmark of diabetes and is a potential determinant of left ventricular
      diastolic dysfunction. OBJECTIVE: To determine whether acute hyperglycaemia can
      induce changes in left ventricular diastolic function in normal subjects similar
      to those observed in insulin-dependent diabetes mellitus (IDDM). DESIGN: Cross
      sectional study. SETTING: London teaching hospital. SUBJECTS: Sixteen twins from
      eight identical twin pairs discordant for IDDM (age 18-38 years, five male) were
      studied; none had a history or evidence of myocardial ischaemia, valvular or
      primary heart muscle disease, systemic hypertension or nephropathy.
      INTERVENTIONS: Non-diabetic twins underwent a hyperglycaemic clamp at 10 mmol/l.
      MAIN OUTCOME MEASURES: Doppler echocardiography was performed in basal condition
      in identical twin pairs discordant for IDDM and repeated in the non-diabetic
      twins during hyperglycaemia. Blood glucose, insulin and catecholamines were
      measured at baseline and during hyperglycaemia. RESULTS: Transmitral Doppler E/A
      velocity ratio was significantly lower in diabetic than non-diabetic twins at
      baseline (1.44 (0.38) vs. 1.51 (0.19), P<0.05). Glucose infusion in the non
      diabetic twins resulted in an increase in their E/A ratio (1.51 (0.19) vs. 1.82
      (0. 47), P<0.05) due to an increase in E velocity (68 (12) to 64.7 (10. 7),
      P<0.05) and a decrease in the peak A velocity (42.7 (3.85) to 38. 0 (4.1),
      P<0.05). No significant changes were observed in peak E velocity or isovolumic
      relaxation time in the non-diabetic twins between baseline and hyperglycaemia.
      CONCLUSIONS: The alterations in left ventricular diastolic function induced by
      acute hyperglycaemia and consequent increase in plasma catecholamines do not
      mimic those demonstrated in IDDM patients.

PMID- 10962114
TI  - Prospective evaluation of the Batista procedure with circulating atrial
      natriuretic peptides.
AB  - A proposed treatment of end-stage heart disease is partial left ventricular
      resection (i.e., Batista procedure). To determine if congestive heart failure
      objectively improves after this procedure, we prospectively evaluated partial
      left ventriculectomy with objective plasma markers of the severity of congestive
      heart failure (i.e., three N-terminal atrial natriuretic peptide prohormone
      radioimmunoassays and atrial natriuretic peptide radioimmunoassay) prior to and
      during the 12 months after partial left ventriculectomy. The four measured atrial
      natriuretic peptides improved in 30% of the subjects at 1 month post-surgery.
      Eighty percent of the subjects, however, had higher circulating atrial
      natriuretic peptides (P<0.01) at 3, 6, and 12 months than prior to surgery
      indicating that their congestive heart failure was objectively worse than prior
      to surgery. Likewise, at 3, 6, and 12 months post-surgery the ejection fractions
      were not significantly better than prior to surgery. By 6 months the subjects
      with the highest circulating atrial natriuretic peptides had died (60% of
      subjects). In conclusion, congestive heart failure improves within 1 month in
      some patients but then deteriorates at 3, 6, and 12 months after the Batista
      procedure. There was no survival benefit with 60% of the patients expiring within
      6 months after the Batista procedure.

PMID- 10962115
TI  - Echocardiographic spectrum of congenitally unguarded tricuspid valve orifice and
      patent right ventricular outflow tract.
AB  - A series of nine consecutive patients with unguarded tricuspid valve orifice as a
      result of partial or complete agenesis of the valvar tissue and patent right
      ventricular outflow tract is reported. Clinical manifestations were cyanosis,
      severe right ventricular failure and incidental echocardiographic detection in a
      young patient with dilated cardiomyopathy. This series contains the oldest
      reported patient with this malady, who was misdiagnosed as portal hypertension
      for 10 years. This study, with possibly the largest number of patients reported
      so far, sheds some light on the natural history of a rare entity.

PMID- 10962116
TI  - Lack of association of serum lipoprotein (a) levels with type-2 diabetes mellitus
      in patients with angiographically defined coronary artery disease.
AB  - Multiple studies have demonstrated that elevated serum lipoprotein (a) [Lp(a)]
      levels are independent predictors for coronary artery disease (CAD) in subjects
      without diabetes mellitus (DM). However, their contribution in patients with DM
      is controversial and still requires clarification. We determined serum Lp(a)
      levels in 355 consecutive Caucasian patients (271 men and 84 women) with
      angiographically documented CAD, and in 100 control subjects (58 men and 42
      women) who were clinically free of cardiovascular disease. In addition, the
      association of serum Lp(a) levels with type-2 DM in patients with CAD was
      investigated after reassigning patients according to the diagnosis of type-2 DM
      (61 men and 40 women with type-2 DM and 210 men and 44 women without). No gender
      differences in Lp(a) levels were observed between men and women (patients and
      control subjects). Patients with CAD had higher Lp(a) levels than the control
      subjects (33 (14-74) vs. 13 (9-29) mg/dl, P<0.001). Elevated Lp(a) levels
      (defined as >90th percentile of controls) were significantly more prevalent in
      men and women with CAD (35% and 28%, respectively) than in control subjects (13%
      and 10%, respectively). Serum Lp(a) levels correlated with LDL cholesterol
      (r=0.22, P<0.001) and apo B levels (r=0.18, P<0.03) in patients and control
      subjects. Stepwise discriminant analysis revealed that Lp(a) was an independent
      risk factor for the presence of CAD, independent of smoking, hypertension, type-2
      DM, LDL and HDL cholesterol or apo A1 and B levels. When patients were studied
      according to the spread of CAD (evaluated as the number of narrowed vessels), no
      differences in serum Lp(a) levels were observed, nor was there a higher
      prevalence of elevated Lp(a) levels. Finally, when patients were re-assigned
      according to the diagnosis of type-2 DM, no effect of apo B and LDL-C levels on
      Lp(a) was found (r=0.06, P=n.s. and 40.14, P=n.s., respectively) and serum Lp(a)
      levels neither associated nor contributed to the extent of CAD. Our results
      showed that serum Lp(a) levels are increased in patients with angiographically
      documented CAD, but there were no significant differences between diabetic and
      non-diabetic patients, which indicates that elevated Lp(a) levels are
      specifically associated with CAD but not with type-2 DM.

PMID- 10962117
TI  - Lipoprotein (a) and cardiovascular risk.

PMID- 10962118
TI  - Long-term lifestyle changes maintain the autonomic modulation induced by
      rehabilitation after myocardial infarction.
AB  - The altered autonomic balance observed after myocardial infarction is shifted
      toward a higher parasympathetic tone by rehabilitation. This effect persists
      after 1 year, however we observed a discrete variability in the long-term
      sympathovagal balance among patients. We postulated that such variability derives
      from the disparate adherence of patients to lifestyle prescriptions regarding
      exercise continuance and smoking avoidance. To test this hypothesis, we reviewed
      the data of 40 patients, who completed with a favourable autonomic modulation the
      initial rehabilitation phase after myocardial infarction and underwent the annual
      follow-up. One year after infarction, 23 patients complied to the advice about
      regular exercise and smoking avoidance (adherent, Group 1); 17 did not (non
      adherent, Group 2). Groups were similar for age, site of infarction, left
      ventricular function, stress test duration and therapy. The ratio LF/HF, derived
      from the power spectral density of RR intervals variability, was used as an index
      of the sympathovagal balance. It was obtained from 15 min of ECG at rest,
      assessed 1 month after MI (baseline), and repeated 3 months (rehabilitation) and
      1 year (follow-up) afterwards. Rehabilitation increased parasympathetic tone in
      all patients, reducing LF/HF by 33%. At follow-up, this potentially favourable
      autonomic profile persisted only in Group 1 patients. In conclusion, after a
      first myocardial infarction, the persistence of the potentially beneficial effect
      of rehabilitation on the sympathovagal balance depends on the compliance to the
      lifestyle changes proposed during the initial phase.

PMID- 10962119
TI  - Prognostic value of left ventricular hypertrophy and geometry in patients with a
      first, uncomplicated myocardial infarction.
AB  - BACKGROUND: The prognostic impact of left ventricular (LV) geometry on
      cardiovascular risk for patients with a first, uncomplicated acute myocardial
      infarction (AMI), and echocardiographic ejection fraction > or =50% has not been
      well described. METHODS AND RESULTS: Accordingly, 111 AMI consecutive patients
      (mean age 59.3+/-10 years) performed echocardiographic examination at
      predischarge. LV mass was calculated by means of Devereux's formula and
      subsequently indexed by body surface area. Fifty-three patients had LV
      hypertrophy and 58 patients had normal LV mass. The two groups were homogeneous
      for demographic, clinical and angiographic variables as well as for the incidence
      of residual ischemia on predischarge stress testing. During follow-up period
      there were 24 cardiac events (cardiac death, unstable angina and non-fatal
      reinfarction) in the 53 patients with LV hypertrophy and only four events in the
      remaining 58 patients without LV hypertrophy (RR=2.45; CI=1.76-3.41; P<0.0001).
      The patients with concentric LV hypertrophy showed a higher incidence of events
      (64%) than patients with eccentric LV hypertrophy (32%, P<0. 05) and patients
      with normal geometry and mass (6%, P<0.0001). Multivariate Cox regression model
      identified concentric geometry as the most powerful predictor of combined end
      points (chi(2)=32.7, P<0. 0001). CONCLUSIONS: An increased LV mass and concentric
      geometry resulted important independent markers of an adverse outcome in patients
      with a first, uncomplicated myocardial infarction and good LV function.

PMID- 10962120
TI  - Pediatric cardiac surgery after exclusively echocardiography-based diagnostic
      work-up.
AB  - This study was performed to evaluate the accuracy of exclusively non-invasive
      preoperative diagnostic work-up based on echocardiography and to assess the
      safety of cardiac surgery using this diagnostic approach in children with heart
      disease. During a 3. 5-year period, accuracy of preoperative (invasive and non
      invasive) diagnostic work-up was prospectively tested by comparison with the
      intraoperative findings obtained by surgical inspection and transoesophageal
      echocardiography. Included were all consecutive 358 children undergoing cardiac
      surgery (except pulmonary artery bandings and ductus ligations) during the study
      period at our institution. Of the patients, 44% were operated on in infancy, 84%
      of procedures were on cardiopulmonary bypass. Echocardiography as the only
      preoperative imaging modality was used in 231 patients (65%), in the other
      children, a diagnostic catheter was done. Diagnostic errors occurred in 3.9%
      (n=5) of patients after diagnostic catheter and in 6.9% (n=16) of patients with
      echocardiography only. Major diagnostic errors (resulting in prolongation of
      cardiac bypass time) were observed at equal frequency in both groups (1.7% or
      four children in the echo-only group and 1.6% or two patients in the catheter
      group). In no case was the outcome affected by the previously unrecognized
      findings. It was shown that diagnostic cardiac catheterization could be avoided
      in a majority of pediatric patients prior to surgical palliation or correction of
      cardiac defects, without increasing the risk of complications or the overall
      outcome.

PMID- 10962121
TI  - Associations between classical cardiovascular risk factors and coronary artery
      disease in two countries at contrasting risk for myocardial infarction: the PRIME
      study.
AB  - PURPOSE: In two countries with contrasting risk for coronary artery disease (CAD)
      Northern Ireland and France-a case-control study was performed on baseline data
      within a cohort study to compare the strength of the associations between CAD
      prevalence and classical risk factors. METHOD AND RESULTS: A sample of 9561 men,
      aged 50-60 years, was studied: 382 had had myocardial infarction or angina, and
      9179 were controls. In both countries, variables associated with CAD were age,
      body mass index, hypertension, diabetes, family history of myocardial infarction
      (MI), tobacco consumption, triglycerides, HDL-cholesterol, apolipoprotein A-I and
      B levels. Logistic regression analyses were conducted using standardized odds
      ratios. The strength of the associations with CAD was rather similar in the two
      countries (Northern Ireland versus France) for age [1.26 (1.10-1. 45) vs. 1.41
      (1.17-1.69)], family history of MI [1.50 (1.04-2.15) vs. 1.83 (0.99-3.37)],
      hypertension [1.49 (1.13-1.97) vs. 1.67 (1.14-2. 44)], diabetes [5.42 (2.53
      11.60) vs. 2.24 (1.06-4.73)], tobacco consumption [1.43 (1.27-1.60) vs. 1.39
      (1.22-1.58)], HDL-cholesterol [0.80 (0.68-0.94) vs. 0.86 (0.70-1.06)] and
      triglyceride levels [1. 17 (1.01-1.36) vs. 1.10 (0.91-1.32)]. Discrepancies
      concerned lipoprotein(a) [1.22 (1.06-1.40) vs. 0.96 (0.81-1.15), P<0.01], with
      stronger associations in Northern Ireland than in France. CONCLUSION: It is
      concluded that the higher prevalence of CAD in Northern Ireland cannot be
      explained by major differences in the susceptibility to classical risk factors;
      the difference in risk of CAD appears mainly related in Northern Ireland to other
      risk factors including a worse lipid profile and genetic/environmental
      interactions.

PMID- 10962122
TI  - Electrocardiography in primary care; is it useful?
AB  - Little is known about the value of electrocardiography in primary care. AIMS: To
      assess whether electrocardiography (ECG) is a useful instrument, in addition to
      history taking and physical examination, in that it changes the general
      practitioner's management of patients with suspected cardiovascular symptoms or
      disease. METHODS AND RESULTS: We performed a prospective study in a group
      practice of eight general practitioners in The Netherlands. During 2 years all
      ECGs that were recorded in these practices were studied. Two questionnaires were
      filled out by the general practitioners, one before and one after the ECG
      recording, to determine indication for electrocardiography, the general
      practitioner's anticipated management before and after ECG results, and the
      subjective usefulness according to the applying doctor. All ECGs were reviewed by
      an experienced general practitioner working in the group practice and later on by
      a cardiologist. In addition, all clinical information, including the 6 months
      follow-up period, was scrutinised by both the cardiologist and general
      practitioner to establish the patients' prognosis. A total of 301 ECGs was
      included in the analysis. Main indications for electrocardiography were chest
      pain (57%), and collapse or palpitation (30%). In 92 (30.6%; 95% CI 25.4-35.8)
      patients a change in management by the general practitioner occurred following
      the ECG results. Most prevalent changes were non-referral to a cardiologist,
      while referral was anticipated before the ECG results (34%), referral while the
      patient would not have been referred without ECG results (20%), and change in
      cardiovascular therapy (40%). In one of these cases only, this change could be
      considered unfavourable, since a subendocardial infarction, not detectable on the
      ECG, was missed. In patients with chest pain, a normal ECG (likelihood ratio (LR)
      0.06) and an abnormal ECG (LR 13.3) were very useful to distinguish between
      patients likely or unlikely to experience cardiac events in the near future. The
      mean subjective usefulness, on a scale of 0-100, of the ECG evaluation according
      to the applying general practitioner was 77. 5 (S.D. 14.4). There was good
      agreement in ECG interpretation between the experienced general practitioner, the
      cardiologist and a second general practitioner. CONCLUSION: Electrocardiography
      in addition to history taking and physical examination, may be an important tool
      in primary care. It can reduce considerably the number of unnecessary referrals.

PMID- 10962123
TI  - The relationship of late potentials to assessment of heart rate variability in
      post-infarction patients.
AB  - In order to investigate the relationship of late potential (LP) to assessment of
      heart rate variability (HRV) after acute myocardial infarction (AMI), we studied
      101 Chinese patients with AMI (10+/-2.4 days) in Taiwan by collecting 24-h ECG
      from a Holter tape recorder and signal-averaged ECG from a high-resolution ECG
      cart. Of the 101 patients, 36 patients had LP (LP group) and 65 patients did not
      (NLP group). The mean heart rate was significantly lower in the LP group than in
      the NLP group (P<0.05). The LP group had a significantly increased high-frequency
      (HF) spectral component of HRV compared with the NLP group (P<0.005), but their
      low-frequency (LF) to HF ratio (LF/HF) was lower (P<0.05). Analysis of the
      circadian variation of HRV revealed significant difference of morning SDRR
      (standard deviation of normal RR intervals) compared with noon SDRR (P<0.05 in
      the LP group, P<0.005 in the NLP group) and evening SDRR (P<0.05 in the LP group,
      P<0.005 in the NLP group). In the NLP group, morning HF (normalized unit, nu) was
      0.258+/-0.098 compared with noon HF (nu) of 0.219+/-0.83 (P<0.05) and evening HF
      (nu) of 0. 225+/-0.085 (P<0.05). Nine patients died during follow-up from cardiac
      causes, three (8.3%) in the LP group and six (9.2%) in the NLP group. In post-MI
      patients, there was higher vagal tone in patients with late potentials compared
      to those without late potentials. NLP patients had more circadian change in vagal
      tone compared with LP patients.

PMID- 10962124
TI  - Different response of patients with idiopathic and ischaemic dilated
      cardiomyopathy to exercise training.
AB  - We looked at the benefits and complications of a home-based exercise programme in
      patients with ischaemic and idiopathic dilated cardiomyopathy. Twenty-four
      patients with left ventricular end-diastolic dimension >6.5 cm and fractional
      shortening <25% entered a cross-over trial of 8 weeks training versus 8 weeks
      rest. Echocardiography, electrocardiogram and cardiopulmonary exercise testing
      were performed at baseline, after training and after detraining. Training
      resulted in a higher peak oxygen consumption (26.5 versus 21.3 ml/kg/min,
      P=0.004), a higher peak heart rate (161 versus 152 bpm, P=0.02) and improved well
      being. Patients with idiopathic dilated cardiomyopathy showed a significant
      increase in exercise time (879 versus 828 s, P=0.03) and peak oxygen consumption
      (31.3 versus 24.3 ml/kg/min, P=0.02) and a decrease in left ventricular end
      diastolic dimension (6.4 versus 6.9 cm, P=0.01) and end-systolic dimension (5.3
      versus 5.8 cm, P=0.04) in contrast to those with coronary artery disease, who
      developed a reduction in septal excursion and shortening rate following training.
      Complications of training were more common in those patients with ischaemic
      cardiomyopathy, greater left ventricular dimensions, poorer exercise tolerance
      and greater ventilation drive at baseline, and included fluid retention and
      exercise-induced ventricular tachycardia. We found that this group of patients
      with a dilated, poorly functioning left ventricle can safely derive benefit from
      a home-based exercise programme, particularly those of idiopathic origin, but
      they should be closely monitored for the development of complications.

PMID- 10962125
TI  - A new beginning.

PMID- 10962126
TI  - Some radical queries.
AB  - A little over 500 years ago, Vasco da Gama arrived on the west coast of India
      after the first direct sea voyage from Portugal with the intention of developing
      trade in spices, particularly in black pepper. Portugese took the merchandise,
      and much more; they ended up colonizing Goa. In 1999 delegates from all over the
      world came to this fabulous Goa for a symposium on antioxidants, some of which
      are natural products found in spices. Some views and queries on the interaction
      of antioxidants and radicals are presented.

PMID- 10962127
TI  - Phospholipid signaling in apoptosis: peroxidation and externalization of
      phosphatidylserine.
AB  - The role of phospholipids in apoptosis signaling and the relationship between
      oxidation of phosphatidylserine and its redistribution in the plasma membrane
      were studied. A novel method for detection of site-specific phospholipid
      peroxidation based on the use of cis-parinaric acid as a reporter molecule
      metabolically integrated into membrane phospholipids in living cells was
      employed. When several tissue culture cell lines and different exogenous oxidants
      were used, the relationship between the oxidation of phosphatidylserine and
      apoptosis has been revealed. The plasma membrane was the preferred site of
      phosphatidylserine oxidation in cells. It was shown that selective oxidation of
      phosphatidylserine precedes its translocation from the inside to the outside
      surface of the plasma membrane during apoptosis. A model is proposed in which
      cytochrome c released from mitochondria by oxidative stress binds to
      phosphatidylserine located at the cytoplasmic surface of the plasma membrane and
      induces its oxidation. Interaction of peroxidized phosphatidylserine with
      aminophospholipid translocase causes inhibition of the enzyme relevant to
      phosphatidylserine externalization.

PMID- 10962128
TI  - Mechanisms of apoptosis in rat cerebellar granule cells induced by hydroxyl
      radicals and the effects of EGb761 and its constituents.
AB  - In this study investigation is made on whether oxidative stress produced by
      treatment with hydroxyl radicals can induce apoptosis in rat cerebellar granule
      cells. The protective effects of Ginkgo biloba extract (EGb761) and its active
      constituents against apoptosis are also examined. The results show that hydroxyl
      radicals generated by the Fenton reaction induced apoptosis in cerebellar granule
      cells, which was associated with the decrease in the Bcl-2 mRNA level and the
      increase in the protein levels of the transcription factors Fos and Jun.
      Moreover, hydroxyl radicals induced time-dependent lipid peroxidation in cells
      and caused the changes in the sulfhydryl group binding sites on the membrane
      proteins. Hydroxyl radicals may induce apoptosis via different signaling
      pathways. EGb761 attenuated these changes and its different constituents showed
      different effects. The total flavonoid component of EGb761 and a mixture of
      flavonoids and terpenes protected cerebellar granule cells from oxidative damage
      and apoptosis induced by hydroxyl radicals. Total terpenes of EGb761 did not
      protect against apoptosis. Flavonoids and terpenes did not show a synergistic
      effect in this regard.

PMID- 10962129
TI  - Apoptotic cell death during ischemia/reperfusion and its attenuation by
      antioxidant therapy.
AB  - Apoptosis is a form of programmed cell death that can be induced in susceptible
      cells by a wide variety of normal physiological stimuli as well as by deleterious
      environmental conditions and cytotoxic agents. The common inducers of apoptosis
      include oxygen free radicals/oxidative stress and Ca(2+) which are also
      implicated in the pathogenesis of myocardial ischemic reperfusion injury. To
      examine how free radicals are directly involved in apoptosis, rats were divided
      into three groups. The first group of rat hearts were perfused for 15 min with
      KHB buffer, the second group of rat hearts were perfused with superoxide
      dismutase plus catalase, and the hearts were subjected to 30 min of ischemia and
      120 min of reperfusion. The third group of rat hearts, served as control which
      were subjected to 165 min of perfusion with KHB buffer (where n=6 rats in each
      group). At the end of each experiment, hearts were saved (at -70 degrees C) and
      analysed for apoptosis, DNA laddening and MDA production. During the reperfusion
      continuous cardiac pressure measurements were recorded in real time with a data
      acquisition and analysis system (CORDAT II, Triton Technologies). Direct
      measurements of heart rate, developed pressure and the first derivative of the
      developed pressure were recorded before the intervention and during the
      reperfusion. Coronary flow was measured by timed collection of coronary effluent.
      The results of our study revealed apoptotic cells after 120 min of reperfusion as
      demonstrated by the intense fluorescence of the immunostained digoxigeninlabeled
      genomic DNA when observed under fluroscence microscopy. Evaluation of DNA
      fragmentation showed increased ladders of DNA bands in the same reperfused hearts
      representing integer multiples of the internucleosomal DNA, about 180 bp. The
      presence of apoptotic cells and DNA fragmentation in the myocardium were
      abolished by preperfusing the hearts in the presence of SOD and catalase, which
      also reduced the oxidative stress as evidenced by the MDA production. In concert,
      myocardial function was significantly better when compared with the ischemic
      control. Taken together, these results clearly demonstrate that oxidative stress
      developed in the ischemic reperfused myocardium induces apoptosis and free
      radical scavengers can play a crucial role in apoptotic cell death associated
      with ischemia/reperfusion.

PMID- 10962130
TI  - Antioxidant activity of nasunin, an anthocyanin in eggplant peels.
AB  - The free radical scavenging activities and inhibitory effect of lipid
      peroxidation of a delphinidin derivative in eggplant were investigated.
      Delphinidin-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin, was
      isolated as purple colored crystals from eggplant peels. Using electron spin
      resonance spectrometry and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), hydroxyl
      radicals (OH) or superoxide anion radicals (O(2)(-)) generated by the Fenton
      reaction or the hypoxanthine-xanthine oxidase system were measured as DMPO-OH or
      DMPO-OOH spin adducts. L-Ascorbic acid 2-[3, 4-dihydro-2,5,7,8-tetramethyl-2
      (4,8, 12-trimethyltridecyl)-2H-1-benzopyran-6yl-hydrogen phosphate] potassium
      salt (EPC-K1) and bovine erythrocyte superoxide dismutase (SOD) were used as
      standards for OH and O(2)(-) scavengers, respectively. Nasunin showed potent
      O(2)(-) scavenging (143+/-8 SOD-equivalent U/mg) and OH scavenging (0. 65+/-0.07
      EPC-K1-equivalent micromol/mg) activities. Then, by changing the concentration of
      DMPO to vary the trapping rate of OH, the presence of a competitive reaction
      between nasunin and OH was studied. The 50% inhibition dose (ID(50)) obtained
      from the inhibition curve did not change, indicating OH scavenging of nasunin is
      not due to direct scavenging but inhibition of OH generating system by chelating
      ferrous ion. Nasunin protection against H(2)O(2)-induced lipid peroxidation in
      rat brain homogenate was measured at 586 nm using the indicator of malonaldehyde
      and 4-hydroxyalkenals. Nasunin (<50 microM) protected against lipid peroxidation
      of brain homogenates. The findings suggest that nasunin is a potent O(2)(-)
      scavenger and has protective activity against lipid peroxidation.

PMID- 10962131
TI  - Effects of selenium deficiency on the response of cardiac tissue to ischemia and
      reperfusion.
AB  - Over a 10-week period, female Wistar rats received a diet containing a low level
      of selenium, cofactor of the antioxidant enzyme glutathione peroxidase (GPx) in
      order to examine the influence of deficiency of this trace element (i) on tissue
      antioxidant enzyme defence systems, and (ii) on the susceptibility of the
      myocardium to ischemia-reperfusion injury. At the end of the dietary treatment,
      hearts were perfused at constant flow (11 ml/min) before being subjected to 15
      min of global normothermic ischemia, followed by 30 min of reperfusion. The
      effects of selenium deficiency were estimated by studying functional recovery of
      various cardiac parameters (left ventricular developed pressure LVDevP, heart
      rate HR, and the product HR x LVDevP), as well as ultrastructural tissue
      characteristics. Furthermore, superoxide dismutase (SOD) and glutathione
      peroxidase (GPx) activities were measured at the end of the reperfusion period.
      Results suggest that: (a) the activity of GPx is decreased by selenium deficiency
      while SOD activity remains unchanged, (b) the recovery of cardiac function and
      myocardial ventricular ultrastructure during reperfusion are altered in the
      selenium-deficient group compared to controls. These results illustrate the
      crucial role that selenium, the co-factor of one of the major antioxidant enzymes
      of the myocardium, plays in determining the vulnerability of the heart to
      ischemia and reperfusion.

PMID- 10962132
TI  - Nitrosative stress in primary glial cultures after induction of the inducible
      isoform of nitric oxide synthase (i-NOS).
AB  - Primary glial cultures are able to express the inducible isoform of nitric oxide
      synthase (i-NOS) upon stimulation by bacterial lipopolysaccharides (LPS) and
      gamma-interferon (gamma-IfN). Immunocytochemical studies revealed, that under our
      experimental conditions i-NOS is expressed exclusively by the microglial cells
      and not in the astrocytes. Nitric oxide (NO) formation represents an oxidative
      load for the microglial cells, as observed by the oxidation rate of the ROS- and
      peroxynitrite indicator dichloro-dihydrofluorescein (DCF-H) in these cells.
      However, cell viability was not affected by the nitric oxide formation,
      indicating some form of protection against the higher oxidative load.
      Upregulation of Mn-SOD in the mitochondria in the course of the induction of i
      NOS and, compared to the astrocytes, higher GSH levels in the microglial cells
      probably explain the resistance of the cultures against nitrosative stress.
      Increased SOD-activities in the mitochondria could lower the superoxide
      concentration in this organelle and may prevent an oxidative and/or nitrosative
      damage via a decreased peroxynitrite formation. The higher GSH-levels in the
      microglial cells of unstimulated cultures represents a buffer which, under the
      conditions of i-NOS catalyzed NO-formation, prevents a decline of the microglial
      GSH-levels below that of the astrocytes.

PMID- 10962133
TI  - The efficacy of an antioxidant cocktail on lipid peroxide level and superoxide
      dismutase activity in aged rat brain and DNA damage in iron-induced epileptogenic
      foci.
AB  - Mixed natural antioxidants can be combined in a prophylactic food against age
      related disease involving reactive oxygen species. beta-Catechin is an
      antioxidant drink, having free radical scavenging activities. It contains green
      tea extract as a main component as well as ascorbic acid, sunflower seed extract,
      dunaliella carotene and natural vitamin E. In the present study, we examined the
      effect of beta-catechin on lipid peroxide formation and superoxide dismutase
      (SOD) activity in aged rat brain and the effect on 8-hydroxy-2'-deoxyguanosine (8
      OHdG) in ipsilateral cortex, 30 min after ferric chloride solution was injected
      into the left cortex of rats. beta-Catechin solution was orally administered to
      aged rats and normal rats for 1 month. One-month administration of beta-catechin
      solution increased SOD activity in the mitochondria fraction of striatum and
      midbrain and decreased thiobarbiturate reactive substance formation in the cortex
      and cerebellum of aged rats. It also inhibited 8-OHdG formation in the
      ipsilateral cortex 30 min after injection of ferric chloride solution. These
      results suggest that beta-catechin is a suitable prophylactic beverage against
      age-related neurological diseases associated with reactive oxygen species.

PMID- 10962134
TI  - Skin low molecular weight antioxidants and their role in aging and in oxidative
      stress.
AB  - The overall skin low molecular weight antioxidant (LMWA) capacity was evaluated
      during the aging process and following exposure to oxidative stress. Several
      invasive and non-invasive techniques were developed for evaluating total
      antioxidant activity. It was found that the skin possesses an extremely efficient
      and unique antioxidant activity that is better than other tissues. During the
      aging process a significant decrease in the levels and activity of the water
      soluble LMWA was detected while no change and even a slight increase was recorded
      for the lipophilic LMWA. Similar results were obtained following exposure to
      oxidative stress. A significant decrease in the water soluble LMWA was recorded
      in all the stress induced procedures indicating a common mechanism of response.
      It has also been shown that along with the reduction in total water soluble
      antioxidant activity there is an accumulation of oxidized adducts. This was
      observed both on the surface of the skin and in deeper layers. It has been found
      that skin releases LMWA from its surface. This secretion phenomenon was found to
      be age dependent. Following exposure to oxidative stress of various kinds, the
      release of LMWA from the skin was significantly enhanced. This may suggest a
      physiological mechanism of the skin to cope with oxidative stress, which would
      open new possibilities for intervention.

PMID- 10962135
TI  - Lipoic acid reduces ischemia-reperfusion injury in animal models.
AB  - Hypoxia and reoxygenation were studied in rat hearts and ischemia and reperfusion
      in rat hindlimbs. Free radicals are known to be generated through these events
      and to propagate complications. In order to reduce hypoxic/ischemic and
      especially reoxygenation/reperfusion injury the (re)perfusion conditions were
      ameliorated including the treatment with antioxidants (lipoate or
      dihydrolipoate). In isolated working rat hearts cardiac and mitochondrial
      parameters are impaired during hypoxia and partially recover in reoxygenation.
      Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration,
      keeps the pH higher (7. 15) during hypoxia as compared to controls (6.98). The
      compound accelerates the recovery of the aortic flow and stabilizes it during
      reoxygenation. With dihydrolipoate, ATPase activity is reduced, ATP synthesis is
      increased and phosphocreatine contents are higher than in controls. Creatine
      kinase activity is maintained during reoxygenation in the dihydrolipoate series.
      Isolated rat hindlimbs were stored for 4 h in a moist chamber at 18 degrees C.
      Controls were perfused for 30 min with a modified Krebs-Henseleit buffer at 60
      mmHg followed by 30 min Krebs-Henseleit perfusion at 100 mmHg. The dihydrolipoate
      group contained 8.3 microM in the modified reperfusate (controlled reperfusion).
      With dihydrolipoate, recovery of the contractile function was 49% (vs. 34% in
      controls) and muscle flexibility was maintained whereas it decreased by 15% in
      the controls. Release of creatine kinase was significantly lower with
      dihydrolipoate treatment. Dihydrolipoate effectively reduces reoxygenation injury
      in isolated working rat hearts. Controlled reperfusion, including lipoate,
      prevents reperfusion syndrome after extended ischemia in exarticulated rat
      hindlimbs and in an in vivo pig hindlimbs model.

PMID- 10962136
TI  - Benefits of vitamin E supplementation to Norplant users--in vitro and in vivo
      studies.
AB  - Norplant subcutaneous implantation is a contraceptive method used in Indonesia.
      Endometrial bleeding is one major reason to discontinue the use of Norplant.
      Angiogenic response in the endometrium of Norplant users was found to be lower
      than in women with normal menstrual cycle. This disturbance in the angiogenic
      process may be caused by an imbalance of pro- and antioxidant processes in the
      endometrium of Norplant users. The aim of this study is to investigate the effect
      of vitamin E on the endometrial angiogenic activity and to assess the efficacy of
      vitamin E supplementation in treating endometrial bleeding in Norplant users.
      Subjects for this study were selected from Norplant users with an exposure of at
      least 3 months, with endometrial bleeding and recruited on the basis of fully
      informed consent. TBA reaction was used to measure degradation products of lipid
      peroxidation. The endometrial angiogenic response was assayed according to
      Folkman et al. (Folkman et al., 1989. Nature 239, 58-61). Samples from
      endometrial biopsies were incubated in vitro with vitamin E or placebo before
      angiogenic measurement. For in vivo supplementation, vitamin E 200 mg/day, or
      placebo for 10 days/month were given to the subjects with double blind
      randomisation. The results showed that the blood levels of TBA-reactive
      substances were significantly higher in Norplant users than in controls. In the
      endometrium from Norplant users with bleeding problems, in vitro supplementation
      of vitamin E resulted in a significantly higher angiogenic score than placebo.
      Although a highly significant reduction of bleeding days in both groups, vitamin
      E and placebo, was seen during the 2 months of the study, the number of bleeding
      days was significantly lower in women treated with vitamin E than with placebo.

PMID- 10962137
TI  - Effect of vitamin E on the development of atherosclerosis.
AB  - The development of atherosclerosis is a multifactorial process in which both
      elevated plasma cholesterol levels and proliferation of smooth muscle cells play
      a central role. Numerous studies have suggested the involvement of oxidative
      processes in the pathogenesis of atherosclerosis and especially of oxidised low
      density lipoproteins. Some epidemiological studies have shown an association
      between high dietary intake or high serum concentrations of vitamin E and lower
      rates of ischemic heart disease. Recently, the Cambridge Heart Antioxidant Study
      (CHAOS) reported strong protection by high vitamin E doses against the risk of
      fatal and non fatal myocardial infarction. Here we have shown that incubation of
      vascular smooth muscle cells in the presence of alpha-tocopherol resulted in
      inhibition of cell proliferation and protein kinase C activity. Since beta
      tocopherol and probucol are not inhibitory, the effect of alpha-tocopherol is
      considered due to a non-oxidant mechanism. In order to understand the protective
      role of alpha-tocopherol against atherosclerosis in vivo the following rabbit
      studies were carried out. Atherosclerosis was induced by a vitamin E poor diet
      containing 2% cholesterol in a group of rabbit. The other groups had 2%
      cholesterol in the diet plus 50 mg/kg vitamin E i.m. or 1% probucol or 50 mg/kg
      vitamin E plus 1% probucol. After 4 weeks, aortas were removed and analysed by
      microscopy for atherosclerotic lesions. Samples of the media were analysed for
      protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical
      atherosclerotic lesions, detected by microscopic examination, their media smooth
      muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully
      prevented cholesterol induced atherosclerotic lesions and the induction of
      protein kinase C activity while probucol was not effective. These results show
      that the protective effect of vitamin E against hypercholesterolemic
      atherosclerosis is not produced by an other antioxidant such as probucol and,
      therefore, may not be linked to the antioxidant properties of this vitamin. The
      effects observed at the level of smooth muscle cells in vitro and ex-vivo
      suggests an involvement of signal transduction events in the protective effect of
      vitamin E against atherosclerosis.

PMID- 10962138
TI  - Free radicals and grape seed proanthocyanidin extract: importance in human health
      and disease prevention.
AB  - Free radicals have been implicated in over a hundred disease conditions in
      humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age,
      ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's
      disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and
      AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors
      of neoplastic processes. A large number of synthetic and natural antioxidants
      have been demonstrated to induce beneficial effects on human health and disease
      prevention. However, the structure-activity relationship, bioavailability and
      therapeutic efficacy of the antioxidants differ extensively. Oligomeric
      proanthocyanidins, naturally occurring antioxidants widely available in fruits,
      vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad
      spectrum of biological, pharmacological and therapeutic activities against free
      radicals and oxidative stress. We have assessed the concentration- or dose
      dependent free radical scavenging ability of a novel IH636 grape seed
      proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared
      the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene.
      These experiments demonstrated that GSPE is highly bioavailable and provides
      significantly greater protection against free radicals and free radical-induced
      lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was
      also shown to demonstrate cytotoxicity towards human breast, lung and gastric
      adenocarcinoma cells, while enhancing the growth and viability of normal human
      gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and
      E were examined on tobacco-induced oxidative stress and apoptotic cell death in
      human oral keratinocytes. Oxidative tissue damage was determined by lipid
      peroxidation and DNA fragmentation, while apoptotic cell death was assessed by
      flow cytometry. GSPE provided significantly better protection as compared to
      vitamins C and E, singly and in combination. GSPE also demonstrated excellent
      protection against acetaminophen overdose-induced liver and kidney damage by
      regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress.
      GSPE demonstrated excellent protection against myocardial ischemia-reperfusion
      injury and myocardial infarction in rats. GSPE was also shown to upregulate
      bcl(2) gene and downregulate the oncogene c-myc. Topical application of GSPE
      enhances sun protection factor in human volunteers, as well as supplementation of
      GSPE ameliorates chronic pancreatitis in humans. These results demonstrate that
      GSPE provides excellent protection against oxidative stress and free radical
      mediated tissue injury.

PMID- 10962139
TI  - Glutamine synthetase activities in spinal white and gray matter 7 days following
      spinal cord injury in rats.
AB  - The glial enzyme glutamine synthetase (GS) is critical for central nervous system
      catabolism of glutamate and glutamine production. Upregulation of GS is a
      hallmark of reactive astrocytosis, although such induction following spinal cord
      injury (SCI) has not been reported. This study's purpose was to determine if GS
      activity is increased following SCI. Experimental rats received a complete spinal
      transection at the T5 segment and control rats received a laminectomy only. GS
      activities were determined using an enzymatic microassay. Glutamine levels were
      resolved in semi-adjacent sections. At 7 days following SCI, GS activity
      increased an average of 170-190% in white matter and 15-25% in gray matter
      immediately adjacent to the transection, and 70-90% in white matter and 40-45% in
      gray matter from cervical and lumbar enlargements. Correlative increases in
      glutamine were observed also. These findings further characterize the astrocytic
      response to SCI, which may contribute to altered glutamine metabolism in injured
      spinal tissue.

PMID- 10962140
TI  - Nitric oxide modulates N-methyl-D-aspartate-evoked serotonin release in the raphe
      nuclei and frontal cortex of the freely moving rat.
AB  - The role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-regulated release of
      5-hydroxytryptamine (5-HT) in the frontal cortex and raphe nuclei of freely
      moving rats has been studied using microdialysis with dual probes, one in each
      region of the same animal. In order to do this the selective neuronal nitric
      oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI; 1 mM) and the NO donor S
      nitroso-N-penicillamine (SNAP; 500 microM-5 mM) were used. All drugs were infused
      into the raphe via the dialysis probe. NMDA showed an inverse concentration
      effect on 5-HT release in the raphe with 25 microM decreasing 5-HT release and
      100 microM increasing release. At the same time the converse effect was seen in
      the frontal cortex. Co-infusion of 7-NI abolished the effect of 100 microM but
      not 25 microM NMDA. 7-NI given alone decreased raphe 5-HT release with a
      concomitant increase being seen in the frontal cortex. Low concentrations of SNAP
      infused into the raphe were found to decrease 5HT release locally but increase
      release in the frontal cortex. In contrast the highest concentration of SNAP used
      was found to have the opposite effect in both brain regions. These data suggest
      that NO plays a role in mediating both basal and NMDA-evoked changes in
      serotonergic transmission between the raphe and frontal cortex.

PMID- 10962141
TI  - Binocular neurons in the nucleus lentiformis mesencephali in pigeons: responses
      to translational and rotational optic flowfields.
AB  - The pretectal nucleus lentiformis mesencephali (LM) receives direct input from
      the contralateral retina and is dedicated to the analysis of optic flowfields
      resulting from self-motion. The activity of 126 LM neurons in response to optic
      flow stimuli was recorded. As with previous studies, it was found that most
      neurons (approximately 90%) exhibited direction-selectivity to large-field
      stimuli moving in the contralateral hemifield. However, some neurons
      (approximately 10%) responded to stimulation of both eyes and had receptive field
      structures conducive for detection of particular patterns of optic flow resulting
      from either self-translation or self-rotation. These binocular neurons were
      maximally responsive to panoramic optic flowfields simulating either
      translational or rotational optic flow.

PMID- 10962142
TI  - The HIV glycoproteins gp41 and gp120 cause rapid excitation in rat cortical
      slices.
AB  - Inflammation and associated excitotoxicity may play important roles in various
      neurodegenerative diseases including AIDS dementia. Here we show that exposure of
      rat parietal cortical slices to the HIV glycoproteins gp120 and gp41 triggered
      very rapid releases of the neurotransmitters glutamate and [(3)H]noradrenaline
      (NA), and of the neuromodulator adenosine. Gp41 was more effective than gp120 at
      releasing glutamate and [(3)H]NA, while both glycoproteins were equi-effective at
      releasing adenosine. The responses to gp120 and gp41 declined rapidly to basal
      levels following their removal. It seems possible that rapid, inappropriate
      excitation may occur in the immediate vicinity of HIV infections in the brain,
      possibly producing some of the transient neurological and psychiatric symptoms
      associated with AIDS dementia.

PMID- 10962143
TI  - Analysis of neurogenesis and programmed cell death reveals a self-renewing
      capacity in the adult rat brain.
AB  - The adult central nervous system was thought to be very limited in its
      regenerative potential; however, the discovery that stem cell populations produce
      neurons in the adult brain highlights the dynamics of a previously assumed
      'static' organ. The continuous generation of new neurons in the adult brain,
      nevertheless, leads to the question of whether neurogenesis is counterbalanced by
      an accompanying cell death in the same regions. The objective of this study was
      to stereologically analyze neurogenesis and programmed cell death in adult brain
      regions with known neurogenic activity. Using bromodeoxyuridine (BrdU) to
      identify newborn cells we find that within a few days of BrdU-labeling the adult
      dentate gyrus and olfactory bulb generate high numbers of newborn neurons. More
      importantly, dUTP-nick end labeling (TUNEL) reveals that areas of adult
      neurogenesis also contain high numbers of apoptotic cells. We conclude that
      programmed cell death may have an important regulatory function by eliminating
      supernumerous cells from neurogenic regions and may thus contribute to a self
      renewal mechanism in the adult mammalian brain.

PMID- 10962144
TI  - Rapid transbilayer phospholipid redistribution associated with exocytotic release
      of neurotransmitters from cholinergic nerve terminals isolated from electric ray
      Narke japonica.
AB  - Asymmetric phospholipid distribution between the outer and inner monolayers of
      cholinergic synaptosomal membranes at rest and their redistribution upon
      depolarization-induced acetylcholine (ACh) release were investigated.
      Translocation of phospholipids between the monolayers was measured using
      fluorescence-labeled phospholipid probes, NBD-PS, NBD-PE, and NBD-PC. The
      percentage of probes in the inner leaflet at equilibrium in synaptosomes at rest
      was estimated to be 63% (NBD-PS), 36% (NBD-PE), and 31% (NBD-PC). Depolarization
      induced exocytosis induced rapid redistribution of these probes. Approximately
      35% of PS and PC in the inner leaflet moved to the outer leaflet, whereas only
      16% of PE moved. To further elucidate the mechanism of exocytosis and membrane
      fusion at presynaptic nerve terminals in the future, the rapid phospholipid
      translocation associated with exocytosis must be taken into account.

PMID- 10962145
TI  - Vocalization thresholds related to noxious paw pressure are decreased by
      paradoxical sleep deprivation and increased after sleep recovery in rat.
AB  - The aim of this study was to assess the effect of paradoxical sleep deprivation
      (PSD) and sleep recovery on the vocalization threshold in rats submitted to a
      mechanical noxious stimulus. Sixteen male Wistar rats were randomly assigned in
      two groups: controls (n=8), paradoxical sleep deprived rats (n=8). PSD was
      performed using the 'inverted flower pot' technique. Paw pressure test was used
      to assess the sensitivity to mechanical noxious stimulus (vocalization
      threshold). The experiment was divided into three periods: baseline (day 1, day
      2), PSD (day 3, day 4, day 5) and recovery (day 6, day 7, day 8, day 9). After 48
      and 72 h of PSD, the vocalization thresholds decreased significantly in
      comparison to the control rats (day 4: 245+/-21 vs. 303+/-20 g, P=0.05; day 5:
      256+/-17 vs. 324+/-22 g, P=0.02). In PSD group, relative to controls,
      vocalization thresholds increased significantly after 48, 72, and 96 h of
      recovery sleep periods (day 7: 378+/-24 vs. 307+/-8 g P=0.01; day 8: 384+/-27 vs.
      316+/-23 g, P=0.02; day 9: 395+/-24 vs. 328+/-15 g, P=0.02). Vocalization
      thresholds on day 6 were not significantly different in both groups (375+/-20 vs.
      324+/-24 g, P=0.08). In conclusion, experimental PSD in rats induces a
      significant decrease in vocalization threshold to mechanical noxious stimulus,
      which is totally reversed during the sleep recovery period.

PMID- 10962147
TI  - Functional suppression of long-term sustained response in the human hippocampal
      formation due to memory distraction.
AB  - Functional magnetic resonance imaging is used to investigate physiological
      dynamics in the human hippocampal formation due to memory distraction. A finger
      movement task executed following a verbal memory task resulted in decreased
      verbal memory scores and shortening of active response in the hippocampal
      formation and the cerebellar dentate nucleus. Verbal rehearsal was excluded as an
      explanation because this sustained activation was approximately three-fold longer
      than the duration of the post-task activation observed in classical language
      processing regions such as Wernicke's and Broca's areas. These interference
      phenomena provide a physiological basis of memory distraction in the hippocampal
      formation.

PMID- 10962146
TI  - Antiallodynic effects produced by stimulation of the periaqueductal gray matter
      in a rat model of neuropathic pain.
AB  - It has been well documented that there is opioid resistance in neuropathic pain.
      This indicates that the endogenous opioid system may not be involved effectively
      in modulating neuropathic pain. The present study sought to determine if
      activation of the descending pain inhibition system might produce analgesia in
      the animal neuropathic model we developed. Under ketamine anesthesia, male
      Sprague-Dawley rats were chronically implanted with stimulating electrodes in the
      ventral periaqueductal gray matter (PAG) and both the tibial and sural nerves of
      the sciatic nerve branches were severed. Pain sensitivity was measured with a von
      Frey filament and acetone applied to the sensitive area for 1 week
      postoperatively. Rats with neuropathic pain syndrome after transection of the
      tibial and sural nerves were tested as to the analgesic effects of ventral PAG
      stimulation for an additional two weeks. Electrical stimulation of the ventral
      PAG turned out to be highly effective in alleviating neuropathic pain. Mechanical
      allodynia and cold allodynia were reduced by PAG stimulation. Naloxone reversed
      the antiallodynic effects of ventral PAG stimulation. These results suggest that
      activation of the descending pain inhibition system including the ventral PAG
      reduces neuropathic pain syndrome and that opiates are involved in this system.

PMID- 10962148
TI  - Decrease of neuronal nitric oxide synthase in the cerebellum of aged rats.
AB  - Nitric oxide (NO) is produced as an important neurotransmitter in the central
      nervous system (CNS) to participate in some pathophysiological pathways. In the
      present study, change of neuronal nitric oxide synthase (nNOS) was examined in
      isolated cerebellum of Wistar rats aged from 2 to 24 months. Northern blot showed
      a lower mRNA level of nNOS in rats aged 6, 12 and 24 months than that in rats
      aged 2 months. Western blot analysis also indicated that the expression of nNOS
      protein was lower in rats aged 6, 12 and 24 months than that of 2 months rats.
      However, the activity of nNOS determined by conversion of [(3)H] L-arginine to
      [(3)H] L-citrulline was decreased significantly in rats aged 24 months only.
      These results indicate the decrease of NOS expression in cerebellum of aged rat
      that seems helpful to explain the causes of malfunction in CNS of aged mammalian.

PMID- 10962149
TI  - The spontaneous K-complex during stage 2 sleep: is it the 'forerunner' of delta
      waves?
AB  - The hypothesis that K-complexes (KCs) contribute to the process of
      synchronization leading to Slow-Wave Sleep (SWS) was evaluated by measuring their
      dynamic evolution across sleep cycles and before transitions to rapid eye
      movement (REM) or to SWS. KC density and inter-KC intervals respectively
      decreased and increased across the sleep cycles, revealing linear trends.
      Comparisons among transitions from stage 2 to SWS or to REM sleep showed a
      prevalence of KCs before the shift to SWS as compared to REM. Changes in KC
      density before the shift to SWS were fitted by a linear regression, at variance
      with the transition to REM sleep. Intra-night variations of KCs, paralleling the
      well-known decrease of slow waves across sleep cycles, and intracycle variations
      before shifting to SWS, both converge to indicate that KCs can be considered as
      the forerunner of delta waves.

PMID- 10962150
TI  - iNOS and nitrotyrosine immunoreactivity in amyotrophic lateral sclerosis.
AB  - We carried out an immunohistochemical investigation of the spinal cords of 15
      patients with sporadic amyotrophic lateral sclerosis (ALS), using antibodies to
      inducible nitric oxide synthase (iNOS) and nitrotyrosine; our purpose was to
      search for a possible role of increased oxidative damage in the motor system that
      may contribute to the neurodegenerative process in this disease. Specimens from
      16 patients without any neurological disease served as controls. In the controls,
      normal-appearing neurons and their dendrites were negatively immunostained for
      iNOS. In the ALS patients, most of normal-appearing anterior horn neurons did not
      show iNOS immunoreactivity either in the perikarya or in their dendrites.
      However, many of the degenerated neurons showing central chromatolysis or simple
      atrophy demonstrated focally or diffusely positive iNOS immunoreactivity within
      the perikarya and their neuronal processes. In the neuropil of the anterior
      horns, the reactive astrocytes were more intensely immunostained for iNOS as
      compared with the controls. Some of the swollen proximal axons (spheroids) were
      focally or diffusely immunostained by the antibody. The corticospinal tracts
      demonstrated positive iNOS immunoreactivity of proliferated reactive astrocytes.
      The immunostaining pattern of nitrotyrosine in the anterior horn neurons of the
      spinal cord was similar to that of iNOS. These findings suggest that selective
      nitric oxide-mediated oxidative damage in the motor system plays a part in the
      pathomechanism of the neuronal degeneration in the spinal cord of sporadic ALS.

PMID- 10962151
TI  - Distribution of the gamma-aminobutyric acid(A) receptor complex alpha 5 subunit
      in chick brain. An immunocytochemical and autoradiographic study.
AB  - This work reports the distribution of the gamma-aminobutyric acid(A) (GABA(A))
      receptor complex alpha5 subunit in the chick using an antibody raised against
      this subunit in the rat, an immunoprecipitation study and a comparative
      autoradiographic study using [(3)H]flunitrazepam in the presence of 1 microM
      zolpidem, which is considered to bind only to those areas presenting the alpha5
      subunit. The specificity of the antibody for the chick GABA(A) receptor complex
      alpha5 subunit is supported by the similar bands obtained by Western blotting
      from rat and chick, the immunoprecipitation study and the general agreement in
      the distribution and pattern of labelling of this antibody in both species. The
      immunocytochemical and autoradiographic distributions in both the chick and rat
      are compared and some areas with disagreement between these distributions are
      discussed. The general conclusion is that the alpha5 subunit of the GABA(A)
      complex receptor seems to have been conserved along evolution.

PMID- 10962152
TI  - Adenosine A(2A) receptor mRNA expression in Parkinson's disease.
AB  - The expression of the human adenosine A(2A) receptor was examined by reverse
      transcription polymerase chain reaction in post-mortem human brain tissue that
      was obtained from normal subjects and patients who died with Parkinson's disease.
      Adenosine A(2A) receptor mRNA was detected in both striatal (nucleus accumbens,
      caudate nucleus and putamen) and extrastriatal (globus pallidus and substantia
      nigra) brain regions. A significant decrease in the level of adenosine A(2A)
      receptor mRNA was found in the anterior and posterior caudate nucleus and
      anterior dorsal putamen, whereas a significant increase was observed in the
      substantia nigra pars reticulata of Parkinsonian brain when compared to age
      matched controls. No change in adenosine A(2A) receptor mRNA levels was seen in
      any other brain region examined. This study demonstrates that A(2A) receptor mRNA
      expression is altered in the basal ganglia of patients who died with Parkinson's
      disease and who were receiving treatment with dopaminergic drugs. The adenosine
      A(2A) receptor appears subject to regulation by dopaminergic systems in human
      brain, though these data do not permit a distinction to be made between the
      effects of neuronal degeneration or drug treatment. The adenosine A(2A) receptor
      may therefore form a target for the treatment of basal ganglia disease.

PMID- 10962153
TI  - Morphological distinction between vasodilator and secretomotor neurons in the
      pterygopalatine ganglion of the cat

PMID- 10962154
TI  - Entamoeba sp. (Sarcomastigophora: Endamoebidae) from ostriches (Struthio camelus)
      (Aves: Struthionidae).
AB  - The first case of Entamoeba of the 1-nucleate mature cyst group in birds is
      described. Trophozoites and cysts of Entamoeba have been found in ostriches
      (Struthio camelus) from farms located all over Spain. The cysts are large
      (13.47microm mean diameter); they possess one nucleus when mature, with a large
      endosome and peripheral chromatine arranged in small granules; chromatoid bodies,
      when present, are large and elongated. Trophozoites are large (19. 88microm mean
      diameter), with a clear differentiation between ecto- and endoplasm, this
      containing numerous vacuoles; the nucleus is large and diffuse. The
      characteristics of this amoeba resembles but do not completely fulfill those of
      E. suis and E. chattoni; also, these species are from mammals.

PMID- 10962156
TI  - SCID mice as a tool for evaluation of heteroxenous life cycle pattern of
      Caryospora (Apicomplexa, Eimeriidae) species.
AB  - Adult severe combined immunodeficient (SCID) mice were inoculated with oocysts of
      13 different Caryospora (Protozoa, Apicomplexa) species isolated from the faeces
      of 10 reptilian and three raptorial bird hosts in attempt to test heteroxenous
      life cycle pattern. Only three reptilian isolates originated from viperid snakes,
      namely from Calloselasma rhodostoma, Atheris nitschei and Vipera ursinii induced
      lethal dermal caryosporosis in SCID mice. Neither clinical signs nor
      developmental stages were observed in mice infected with further nine caryosporan
      isolates originated from other reptilian and raptorial bird hosts. Results of
      this study confirmed that SCID mice represent a useful tool for evaluation of
      heteroxenous life cycle pattern of caryosporan coccidia and that only the
      Caryospora species from viperid and crotalid snakes produce dermal caryosporosis
      in mice

PMID- 10962155
TI  - Infection of a canine macrophage cell line with leishmania infantum:
      determination of nitric oxide production and anti-leishmanial activity.
AB  - We have previously shown that resistance to Leishmania infantum in dogs is
      associated with a Th1 type of immune response. In this study, we use a canine
      macrophage cell line (030-D) that can readily be infected with this protozoan
      parasite. Our aim is to further characterize the effector mechanisms involved in
      killing of Leishmania parasite in dogs. We observed that activation of 030-D
      cells by incubation with a supernatant derived from a Leishmania-specific T cell
      line containing IFN-gamma, TNF-alpha and interleukin-2 (IL-2) resulted in
      enhanced nitric oxide (NO) production by these cells. In addition, we observed
      enhanced anti-leishmanial activity of infected 030-cells after activation. Both,
      NO production and anti-leishmanial activity were abrogated by addition of L-N(G)
      nitroargininemethyl ester (L-NAME), an analogue of L-arginine. Thus, NO play an
      important role in the anti-leishmanial activity of these canine macrophages. We
      propose the infection of the 030-D cell line as a good in vitro model to further
      investigate parasite-host cell interactions in dogs, a natural host of Leishmania
      parasites.

PMID- 10962157
TI  - Molecular detection of an Ehrlichia-like agent in rainbow trout (Oncorhynchus
      mykiss) from Northern California.
AB  - Ehrlichia DNA was identified by nested PCR in rainbow trout (Oncorhynchus mykiss)
      collected from a creek in northern California where Potomac horse fever is
      endemic. Ehrlichia DNA was found in tissues from several organs including the
      gills, heart, spleen, liver, kidneys and intestine of trout and from three
      different adult digenetic trematodes (Deropegus sp., Crepidostomum sp.,
      Creptotrema sp.) parasitizing the gallbladder and/or the intestine of the trout.
      Sequencing of PCR-amplified DNA from the 16S rRNA gene indicated that the source
      organism was most closely related to the sequences of E. risticii (level of
      sequence similarity 96.0%), the SF agent (95.9%), E. sennetsu (95.8%), and
      Neorickettsia helminthoeca (95.3%). The data suggest that trout and parasitic
      trematodes may be involved in the epidemiology of an Ehrlichia-like agent
      belonging to the E. sennetsu genogroup. Whether the fish agent infects horses,
      dogs, or human beings, and whether it causes disease, remain to be determined.

PMID- 10962158
TI  - Molecular analysis of Boophilus spp. (Acari: Ixodidae) tick strains.
AB  - Boophilus spp. (Acari: Ixodidae) parasitize cattle and other farm and wild
      animals in tropical and subtropical regions of the world. Ticks belonging to the
      genus Boophilus have undergone evolutionary processes associated with habitat
      adaptation following biogeographical separation, resulting in strains with marked
      morphological differences. We have characterized at the molecular level B.
      microplus strains from Latin America and Australia, employing sequences derived
      from the bm86 coding region, an intron located within the bm86 gene, and DNA
      short tandem repeats (STR). A B. annulatus strain was employed for comparison.
      The results indicated that variation within the bm86 coding region is higher
      between B. microplus strains than between some B. microplus strains and B.
      annulatus. The sequence of the intron was not informative for phylogenetic
      analysis, varying among individuals of the same strain. Two STRs were identified
      in B. microplus (STRs BmM1 and BmM2) and one in B. annulatus (STR Ba1). Southern
      hybridization experiments with STRs BmM1 and BmM2 as a probe revealed the
      prevalence of dispersed moderately repeated DNA in the genome of B. microplus.
      The analysis of polymorphism at STR locus BmM1 evidenced differences within and
      between populations of B. microplus. These results support at the molecular level
      the existing differences between B. microplus strains and suggest tools to
      characterize these populations.

PMID- 10962159
TI  - Cryptosporidium parvum: oocysts purification using potassium bromide
      discontinuous gradient.
AB  - Cryptosporidium parvum oocysts were purified using a discontinuous potassium
      bromide density gradient, composed by three solutions of 6, 16 and 28% (w/v) KBr
      in Tris-EDTA buffer. Fecal samples containing oocysts were washed to diminish
      interfering lipids and applied to the gradient. After centrifugation, oocysts can
      be easily aspirated from a clear band, diluted and washed by centrifugation in
      phosphate buffer to remove residual KBr. This method allows the purification of
      large amounts of highly purified C. parvum oocysts, using low cost reagents and a
      standard table-top centrifuge.

PMID- 10962160
TI  - Quantitative analysis of microfilarial periodicity of Dirofilaria immitis in
      cats.
AB  - Microfilarial periodicity of Dirofilaria immitis in the venous blood of infected
      cats was analyzed by a trigonometric model. Cats were infected by subcutaneous
      transplantation with 120-day-old juvenile D. immitis. Microfilariae in the blood
      were first observed 98 days after transplantation. Blood was collected at 4h
      intervals for a 24h period, and examinations were repeated five times in two
      cats. The calculated periodicity index was 75.1 and 50.3 in these two cats. The
      estimated hour of peak microfilarial density ranged from 1.00 to 2.84h. Thus, the
      periodicity of microfilariae of D. immitis in the blood of cats was characterized
      as nocturnally sub-periodic.

PMID- 10962161
TI  - Epidemiology of ovine oestrosis (OEstrus ovis Linne 1761, Diptera: Oestridae) in
      Sicily.
AB  - A survey for oestrosis was carried out in the slaughterhouse at Messine (Sicily)
      from May 1996 to April 1998. The heads of sheep from local flocks were collected
      each month. A total of 841 heads were examined according to a validated
      procedure. 469 (55.8%) were infested by OEstrus ovis larvae. 4423 larvae were
      harvested: 1829 first instar larvae or L1 (41.4%), 1286 second instar larvae or
      L2 (29.1%) and 1308 third instar larvae or L3 (29.6%). The mean larval burden for
      infected sheep was 9.4 larvae with an average of 3.9 L1, 2.7 L2 and 2.8 L3. No
      period of hypobiosis was recorded. The proportions of larvae in each of the
      different larval stages was similar from January to September, however, from
      October to December the percentage of L1 was higher, indicating a period of
      slowed development. In order to lower the overall prevalence of this disease, it
      would be necessary to use a parasiticide effective against O. ovis, for all
      routine parasite control treatments.

PMID- 10962162
TI  - A comparison of jump performances of the dog flea, Ctenocephalides canis (Curtis,
      1826) and the cat flea, Ctenocephalides felis felis (Bouche, 1835).
AB  - Jump performances of Ctenocephalides canis and Ctenocephalides felis felis have
      been measured and compared on unfed young imagos. The mean length of the C. felis
      felis jump was 19.9+/-9.1cm; minimum jump was 2cm, and the maximum was one 48cm.
      The C. canis jump was significantly longer (30.4+/-9.1cm; from 3 to 50cm). For
      height jump evaluation, grey plastic cylindric tubes measuring 9cm in diameter
      were used. Their height was increasing from 1 to 30cm by 1cm. Groups of 10 fleas
      of the same species were deposited on the base of the tube. The number of fleas
      which succeeded in jumping above the tube was recorded. The mean height jump
      carried out by 50% of fleas was calculated after linearisation of the curves: it
      was 15.5 and 13.2cm for C. canis and C. felis, respectively. The highest jump was
      25 for C. canis and 17cm for C. felis.

PMID- 10962163
TI  - Thrombopoietin in the fetus and neonate.
AB  - C-mpl ligand or thrombopoietin (Tpo) is increasingly recognised as the major
      regulator of platelet homeostasis in humans. Relatively little is known about Tpo
      in the fetus and neonate but no evidence has yet been found to suggest any
      fundamental difference in Tpo structure, function and regulation in the fetus and
      neonate compared to older age groups. Tpo mRNA transcripts have been detected in
      the fetus as early as 6 weeks post conception and the liver appears to be the
      main site of Tpo production in both the fetus and neonate. The vast majority of
      healthy newborns have detectable levels of circulating Tpo and raised Tpo levels
      are commonly, but not consistently, found in thrombocytopenic neonates. In adults
      receptor binding and subsequent metabolism of Tpo is proposed as the main method
      of regulation of the circulating Tpo level. Preliminary studies in neonates
      showing increased Tpo levels most often during thrombocytopenia accompanied by
      reduced megakaryocytopoiesis supports this concept. In addition to this
      demonstrable fetal and neonatal endogenous Tpo production megakaryocyte
      progenitor and precursor cells from the fetus and from preterm and term newborns
      proliferate and differentiate extensively in-vitro in response to exogenous Tpo.
      Furthermore a recent study has shown a marked rise in platelet count in newborn
      rhesus monkeys administered one form of recombinant Tpo. Although these studies
      remain at an early stage together these findings strongly suggest that, as in
      adults, Tpo is the major regulator of platelet homeostasis in the fetus and
      neonate. Thrombocytopenia is common in sick neonates and progress in
      understanding this important clinical problem is likely to be greatly enhanced by
      the current and future research into Tpo production, function and regulation in
      the healthy and thrombocytopenic fetus and neonate.

PMID- 10962164
TI  - Does maternal prenatal attachment predict postnatal mother-infant interaction?
AB  - The current study examined whether maternal prenatal attachment is associated
      with the mother-infant relationship. One hundred pregnant women and their infants
      at 12 weeks participated in the study. The sample was part of the Umea Child and
      Family Development project and was randomly recruited by midwives or health
      visitors. The expectant women completed a self-administered questionnaire, the
      PAI (the Prenatal Attachment Inventory) measuring prenatal attachment towards
      their unborn baby. At about 12 weeks postpartum, mothers and their infants were
      observed and videotaped during an en face interaction. The results revealed that
      maternal prenatal attachment towards the unborn baby is a good predictor of the
      early mother-infant relationship. Mothers who were high on the PAI-factor
      fantasy, for example, in general showed more involvement while interacting with
      their babies. Mothers rated highly on PAI-factors such as interaction and
      affection stimulated their infants by using more proximal stimulation, while
      those rated highly on differentiation of self with the unborn baby used more
      distal stimulation. Maternal responsive behaviour was only predicted by infant
      attentive behaviour. This study demonstrated that maternal prenatal attachment
      during the third trimester of pregnancy is associated with the postnatal maternal
      involvement, and can serve as an important diagnostic aid in identifying those
      women for whom the mother-child interaction is likely to be sub-optimal.

PMID- 10962165
TI  - Effect of morphine on respiratory drive in trigger ventilated pre-term infants.
AB  - The response to morphine (100 microgram (microg)/kg bolus, 10 microg/kg/h
      infusion) of 14 babies (median birth weight/gestation 1. 37 kg/30 weeks) trigger
      ventilated for hyaline membrane disease was compared to a group of 26 babies
      (median birth weight/gestation 1.1 kg/28 weeks) also trigger ventilated for
      hyaline membrane disease but not treated with morphine. The effect of morphine on
      triggered breath rate was very variable with no significant difference between
      the groups seen until 12 h after starting the infusion (mean [95% CI] difference=
      17 [-33, -2] breaths/min). In those babies (n=11) who had plasma morphine levels
      measured there was no significant reduction in triggered rate over time despite
      significantly increasing plasma morphine levels. Babies who produced morphine-6
      glucuronide at 12 h showed a significantly greater reduction in triggered breath
      rate than those who did not (median change -22 breaths/min compared to -4
      breaths/min).

PMID- 10962166
TI  - Determinants of blood pressure in very low birth weight neonates: lack of effect
      of antenatal steroids.
AB  - OBJECTIVES: To define the range of normal blood pressures (BP) for very low birth
      weight (VLBW;</=1500 g) neonates and to study perinatal variables affecting BP
      measurements after birth, including the effects of antenatal steroids. STUDY
      DESIGN: Antenatal steroids were rarely administered at Parkland Memorial Hospital
      before May 1994, permitting us to establish a cohort of VLBW neonates exposed to
      antenatal steroids [n=70, 1166+/-253 (S.D.) g, and 28.7+/-2.1 weeks] who were
      matched with neonates delivered during the prior year (n=46, 1100+/-241 g, 28.9+/
      1.8 weeks). Maternal and neonatal charts were abstracted for pertinent data, and
      neonatal BP measurements (determined directly when an arterial catheter was
      available or indirectly by the oscillometric method) were extracted every 3 h for
      the first 12 h and every 6 h until 72 h postnatal. RESULTS: Antenatal steroids
      did not affect BP immediately after birth or for the subsequent 72 h postnatal.
      Therefore, data from all neonates </=1500 g were combined and the pattern of BP
      change over 72 h postnatal assessed. Systolic, diastolic and mean BP increased
      (P<0.001) 33%, 44% and 38%, respectively, during the first 72 h. Although
      neonates weighing </=1000 g and 1001-1500 g demonstrated gradual increases
      (P<0.001) in systolic, diastolic and mean BP by 72 h, values were consistently
      lower (P<0.01) in neonates </=1000 g. Of interest, only 11 neonates (9.5%) were
      treated for clinical hypotension. CONCLUSIONS: In VLBW neonates antenatal
      steroids do not modify BP measurements either immediately after birth or the 30
      40% rise occurring in the first 72 h postnatal. Further, BP is developmentally
      regulated and is gestationally and birth weight dependent. These data provide
      additional insight into assessing the need for treating hypotension.

PMID- 10962167
TI  - Artificial sweetener reduces nociceptive reaction in term newborn infants.
AB  - BACKGROUND: Sucrose has been shown to have an analgesic effect in preterm and
      term neonates. Sucrose, however, has a high osmolarity and may have deleterious
      effects in infants with fructose intolerance. Furthermore, it may favour caries.
      We therefore investigated the effects of a commercially available artificial
      sweetener (10 parts cyclamate and 1 part saccharin), glycine (sweet amino acid)
      or breast milk in reducing reaction to pain as compared with a placebo. SUBJECTS:
      Eighty healthy term infants, four days old, with normal birth weight.
      INTERVENTIONS: The infants were randomly assigned to one of four groups: 2 ml
      sweetener, glycine, expressed breast milk or water were given 2 min before a heel
      prick for the Guthrie test. The procedure was filmed with a video camera and
      analysed by two observers who did not know which medication the infant had
      received. RESULTS: Using a multivariate regression analysis, the following
      variables had significant correlation with relative crying time and recovery
      time: behavioural state before the intervention, the pricking nurse, and the type
      of medication. Relative crying time and recovery time were significantly less in
      the sweetener group but not in the glycine and the breast milk group.
      CONCLUSIONS: The artificial sweetener used in our study reduces pain reaction to
      a heel prick in term neonates, and thus provides an alternative to sucrose. In
      contrast, glycine tends to increase pain reaction whereas breast milk has no
      effect.

PMID- 10962168
TI  - Factors predicting peri- and neonatal outcome in diabetic pregnancy.
AB  - A population-based birth cohort including 296 consecutive type 1 diabetic births
      in a geographically defined catchment area was used to evaluate factors
      predicting poor perinatal and neonatal outcome. Though perinatal mortality has
      decreased (17.1/1000 births at 28 or more weeks of gestation), the neonatal
      morbidity rate still remains high despite improved maternal metabolic control and
      developed antepartum surveillance. Poor glycemic control during the first weeks
      of pregnancy was the most important risk factor (relative risk (RR) 2.91; 95%
      confidence interval (CI) 1.29-6.55) predicting adverse neonatal events such as
      long (>10 days) stay in the neonatal unit, malformation or perinatal death. The
      risk was further increased in cases of severe diabetes (White class F-R; RR 2.75;
      95% CI 1.59-4.76) and primiparity (RR 1.64; 95% CI 1.02-2.65). By evaluating
      these risk factors at the first antenatal visit, a subgroup with a particular
      need of counselling and intensive feto-maternal monitoring can be identified.

PMID- 10962169
TI  - Development of the auditory brainstem of birds: comparison between barn owls and
      chickens.
AB  - Birds have proved to be extremely useful models for the study of hearing
      function. In particular, chickens and barn owls have been widely used by a number
      of researchers to study diverse aspects of auditory function. These studies have
      benefited from the advantages offered by each of these two species, including
      differences of auditory specialization. Direct comparisons between chickens and
      barn owls become complicated when the degree of auditory specialization and their
      modes of development are brought into consideration. In this article we review
      the available literature on the development of the auditory brainstem of chickens
      and barn owls in the context of such differences. In addition, we present a time
      line constructed on the basis of common stages of structural differentiation,
      rather than chronological time. We suggest that such a time line should be
      considered when discussing comparative data between these two species. Such an
      approach should facilitate the interpretation of similarities and differences
      observed in the developmental processes of the auditory system of chickens and
      barn owls.

PMID- 10962170
TI  - Modification of delayed rectifier potassium currents by the Kv9.1 potassium
      channel subunit.
AB  - Within auditory pathways, the intrinsic electrical properties of neurons, and in
      particular their complement of potassium channels, play a key role in shaping the
      timing and pattern of action potentials produced by sound stimuli. The Kv9.1 gene
      encodes a potassium channel alpha subunit that is expressed in a variety of
      neurons, including those of the inferior colliculus. When cRNA encoding this
      subunit is injected into Xenopus oocytes, no functional channels are expressed.
      When, however, Kv9.1 is co-expressed with certain other alpha potassium channel
      subunits, it changes the characteristics of the currents produced by these
      functional channel proteins. We have found that Kv9.1 isolated from a rat brain
      cDNA library alters the kinetics and the voltage-dependence of activation and
      inactivation of Kv2.1, a channel subunit that generates slowly inactivating
      delayed rectifier potassium currents. The rate of activation of Kv2.1 is slowed
      by co-expression with Kv9.1. With Kv2.1 alone, the amplitude of evoked currents
      increases monotonically with increasing command potentials. In contrast, when
      Kv2.1 is co-expressed with Kv9.1, the amplitude of currents increases with
      increasing depolarization up to potentials of only approximately +60 mV, after
      which increasing depolarization results in a decrease in current amplitude.
      Currents produced by Kv2. 1 alone and by Kv2.1/Kv9.1 are both sensitive to the
      potassium channel blocker tetraethyl ammonium ions (TEA), but higher
      concentrations of TEA (20 mM) eliminate the biphasic voltage-dependence of the
      Kv2.1/Kv9.1 currents. Co-expression with Kv9.1 also produces an apparent negative
      shift in the voltage-dependence of inactivation and activation. Computer
      simulations of model neurons suggest that co-expression of Kv9.1 with Kv2.1 may
      have different effects in neurons depending on whether their firing pattern is
      limited by the inactivation of inward currents. In excitable cells in which the
      inward currents do not inactivate, co-expression with Kv9.1 could produce an
      inhibition of firing during sustained depolarization. In contrast, in model
      neurons with rapidly inactivating inward current, the change in the voltage
      dependence of activation produced by Kv9.1 may allow the cells to follow high
      frequency stimulation more effectively.

PMID- 10962171
TI  - Expression of Shal potassium channel subunits in the adult and developing
      cochlear nucleus of the mouse.
AB  - The pattern of expression of potassium (K(+)) channel subunits is thought to
      contribute to the establishment of the unique discharge characteristics exhibited
      by cochlear nucleus (CN) neurons. This study describes the developmental
      distribution of mRNA for the three Shal channel subunits Kv4.1, Kv4.2 and Kv4.3
      within the mouse CN, as assessed with in situ hybridization and RT-PCR
      techniques. Kv4.1 was not present in CN at any age. Kv4.2 mRNA was detectable as
      early as postnatal day 2 (P2) in all CN subdivisions, and continued to be
      constitutively expressed throughout development. Kv4.2 was abundantly expressed
      in a variety of CN cell types, including all of the major projection neuron
      classes (i.e., octopus, bushy, stellate, fusiform, and giant cells). In contrast,
      Kv4.3 was expressed at lower levels and by fewer cell types. Kv4.3-labeled cells
      were more prevalent in ventral subdivisions than in the dorsal CN. Kv4.3
      expression was significantly delayed developmentally in comparison to Kv4.2, as
      it was detectable only after P14. Although the techniques employed in this study
      detect mRNA and not protein, it can be inferred from the differential
      distribution of Kv4 transcripts that CN neurons selectively regulate the
      expression of Shal K(+) channels among individual neurons throughout development.

PMID- 10962172
TI  - Development and influence of inhibition in the lateral superior olivary nucleus.
AB  - While studies of neuronal development and plasticity have focused on excitatory
      pathways, the inhibitory projection from the MNTB to the LSO provides a favorable
      model for studies of synaptic inhibition. This review covers recent studies from
      our laboratories indicating that inhibitory connections are quite dynamic during
      development. These findings suggest that there are two phases inhibitory
      transmission. During an initial depolarizing phase is growth and branching of pre
      and postsynaptic elements in the LSO. During a second hyperpolarizing phase
      there is refinement of inhibitory afferent arborizations and the LSO dendrites
      that they innervate.

PMID- 10962173
TI  - Differential distribution of glutamate receptors in the cochlear nuclei.
AB  - Glutamate receptors are the major excitatory neurotransmitter receptors of the
      mammalian central nervous system, and include AMPA, kainate, delta, NMDA, and
      metabotropic types. In the cochlear nucleus (CN), the AMPA receptor subunits
      GluR2-4 are found in major kinds of neurons, while GluR1 subunit distribution is
      more restricted. GluR2 is low in the anteroventral CN, suggesting that many AMPA
      receptors here are calcium-permeable. Delta receptors are most prevalent in
      cartwheel cells in the dorsal CN. Of the NMDA receptors, NR1 is widespread while
      the NR2 subunits show more restricted distributions. Of the metabotropic
      glutamate receptors, mGluR1alpha is most prevalent in the dorsal CN, and mGluR2
      is concentrated in Golgi cells and unipolar brush cells. AMPA receptors in
      endbulb synapses in the anteroventral CN are mainly GluR3+4 complexes: probably
      an adaptation for rapid auditory neurotransmission. Glutamate receptors are
      differentially distributed in synapses of fusiform cells of the dorsal CN; GluR4
      and mGluR1alpha are present only at basal dendrite synapses (auditory nerve),
      while other glutamate receptors occupy both apical and basal synapses. Analysis
      of cytoplasmic distribution suggests that a selective targeting mechanism may
      restrict movement of GluR4 and mGluR1alpha to basal dendrites, although other
      targeting mechanisms may be present.

PMID- 10962174
TI  - Differential postsynaptic distribution of GluRs 1-4 on cartwheel and octopus cell
      somata in the gerbil cochlear nucleus.
AB  - Differences were demonstrated in the distribution of glutamate receptors (GluR)
      1, 2, 2/3 and 4 postsynaptic immunoreactivity (PSIR) on the somata of cartwheel
      and octopus cells in the adult gerbil cochlear nucleus (CN). Montages of electron
      micrographs of cartwheel and octopus cells immunoreacted with antibodies to GluR
      1, 2, 2/3 and 4 were prepared. The number of synaptic terminals with PSIR were
      counted on all cells for each antibody, normalized to the total length of somatic
      surface analyzed. The density of terminals apposed to PSIR on octopus cells was
      similar for the antibodies GluR1, 2/3 and 4, but significantly less for GluR2. On
      cartwheel somata the numbers of terminals apposed to immunoreactive postsynaptic
      specializations with GluR1, 2, 2/3 or 4 were not significantly different from
      each other. The density of terminals apposed to GluR2/3 and 4 positive
      postsynaptic specializations was significantly less on cartwheel cells than on
      octopus somata. The data suggest that the decreased presence of the GluR2
      subunit, which confers calcium impermeability to the assembled receptor and
      slower gating kinetics to receptors with a high GluR4 content, is the major
      difference in the AMPA receptors on the somata of these cell types. The presence
      on cartwheel cells of a majority of AMPA receptors which contain GluR2 may
      account for the fact that cartwheel cells respond to shocks to the auditory nerve
      with 100 ms excitatory postsynaptic potentials (EPSPs), while octopus cells, most
      of whose AMPA receptors lack GluR2, respond with 1 ms EPSPs.

PMID- 10962175
TI  - The AMPA receptors of auditory neurons.
AB  - The ionotropic glutamate receptor (GluR) subtype known as the AMPA receptor,
      which mediates rapid excitatory synaptic transmission in many regions of the
      nervous system, is composed of four different protein subunits, termed GluRs 1-4.
      The functional properties of each AMPA receptor are determined by the relative
      levels of GluRs 1-4 and by post-transcriptional modifications of these proteins
      through mRNA editing and alternative exon splicing. The present paper reviews the
      published evidence for (1) localization of mRNAs and immunoreactivity for GluRs 1
      4 in the cochlea and subcortical central nervous system auditory pathways of
      mammals and birds, and (2) involvement of AMPA receptors in synaptic transmission
      in the auditory system. Recent biochemical and electrophysiological evidence
      concerning the specialized properties of AMPA receptors on brainstem auditory
      neurons is also reviewed, along with data concerning how these properties emerge
      during normal development.

PMID- 10962176
TI  - Long-term potentiation in the inferior colliculus studied in rat brain slice.
AB  - The purpose of this study is to determine whether long-term potentiation (LTP)
      can be induced in the central nucleus of the inferior colliculus (ICC) by
      electrical stimulation of the lateral lemniscus. If LTP can be induced, is it
      mediated by N-methyl-D-aspartate (NMDA) and/or other receptors? Brain slices of
      the ICC were obtained from 14-35 day old Wistar rats. The field potentials were
      recorded from the ICC after GABAergic and glycinergic inhibition was suppressed.
      Following tetanic stimulation (50 Hz, 20 s), the amplitude of the response was
      increased to about 146% of control response for at least 30 min. LTP was observed
      in about 78% of the cases tested. Induction of LTP in the ICC required activation
      of both NMDA and gamma-aminobutyric acid (GABA)(B) receptors. GABAergic
      inhibitory postsynaptic potentials (IPSPs) were blocked by the GABA(A) receptor
      antagonist, but not by the GABA(B) receptor antagonist. The IPSPs were decreased
      by the GABA(B) receptor agonist, baclofen. The intrinsic postsynaptic membrane
      properties were not affected by baclofen. These results suggest that GABAergic
      inhibition in the ICC is mediated only by GABA(A) receptors, but that it is
      modulated by presynaptic GABA(B) receptors. The GABA(B) receptors in the ICC may
      suppress GABAergic inhibition and promote induction of LTP.

PMID- 10962177
TI  - Cholinergic receptors: dual roles in transduction and plasticity.
AB  - The regional distributions and possible functions of nicotinic acetylcholine
      receptors (nAChRs) in the developing and adult auditory rat brain are reviewed.
      The predominant nAChR in the auditory brainstem is the alpha7 homomeric receptor.
      alpha7 mRNA and protein are expressed in selected regions of the cochlear nucleus
      (CN), inferior colliculus (IC), medial superior olive, lateral superior olive,
      ventral nucleus of the lateral lemniscus and superior paraolivary nucleus. Peak
      expression of mRNA and protein occurs by the second postnatal week in most
      auditory brainstem areas. In contrast, the alpha3 and beta4 nicotinic subunits
      are expressed in the embryo and early in postnatal development in the CN and IC,
      but not other brainstem nuclei. Of particular interest is the octopus cell region
      of the posteroventral cochlear nucleus (PVCN). alpha3 and beta4 are down
      regulated in the octopus cell region about postnatal day 10, which is the age
      that alpha7 is at peak expression. NAChRs play important roles in transduction
      and in regulating intracellular calcium. The ability of the alpha7 receptor to
      synchronize synaptic activity and stabilize synapses makes it a prime candidate
      as a mechanism underlying homeostatic plasticity in the auditory system.

PMID- 10962178
TI  - Deafferentation-induced changes in protein kinase C expression in the rat
      cochlear nucleus.
AB  - Isoforms of the signal transducing molecule, protein kinase C (PKC), may play a
      role in neural plasticity following sensory deafferentation. To explore the role
      of PKC in central auditory plasticity, we studied the effect of auditory
      deafferentation on the expression of PKC betaI, betaII, gamma, and delta in the
      rat dorsal (DCN) and ventral cochlear nucleus (VCN), using immunocytochemistry.
      Male rats were treated with kanamycin and furosemide to induce hair cell loss. At
      various intervals post-treatment, brains were perfusion-fixed and processed for
      immunocytochemistry. Following deafferentation, we observed a gradual increase in
      PKC betaI immunoreactivity (ir) in the deepest layers of the DCN, possibly
      representing synapses of primary afferents or parallel fibers on unlabeled
      neurons. Correlated with this, we observed an increase in the number of neurons
      in the deep DCN that showed PKC delta ir. In controls, we observed PKC gamma ir
      in small ovoid cells concentrated in the middle layer of the DCN. From days 4
      through 14 after deafferentation, we found an increase in the intensity of
      staining of these cells, with a return toward control levels by day 28. Finally,
      Purkinje-like cells (PLC) in the VCN, which express only PKC delta in control
      rats, began to express PKC gamma after deafferentation, correlated with increased
      expression of calbindin D28k in PLC. Thus PKC isoforms are differentially
      regulated in the CN following deafferentation, supporting a role for PKC in
      auditory plasticity.

PMID- 10962179
TI  - Altered glycinergic synaptic activities in guinea pig brain stem auditory nuclei
      after unilateral cochlear ablation.
AB  - This paper reviews efforts to determine if a unilateral hearing loss altered
      inhibitory glycinergic synapses in the cochlear nucleus (CN) and the superior
      olive. In young adult guinea pigs, 2-147 days after unilateral cochlear ablation,
      we quantified the electrically evoked release and the high-affinity uptake of
      [(14)C]glycine as measures of transmitter release from glycinergic presynaptic
      endings and glycine removal from extracellular spaces. The specific binding of
      [(3)H]strychnine was quantified to measure synaptic glycine receptor activity
      and/or expression. Three types of post-lesion change were observed. First,
      several tissues exhibited changes consistent with a persistent deficiency in
      glycinergic inhibitory transmission. Deficient binding prevailed on the ablated
      side in the anterior and caudal anteroventral CN, the posteroventral CN and the
      lateral superior olive (LSO), while glycine release was near normal and uptake
      was elevated (except in the LSO). However, deficient release prevailed in the
      dorsal CN, bilaterally, and was accompanied by elevated uptake. Second, the LSO
      on the intact side exhibited changes consistent with strengthened glycinergic
      inhibition, as binding was elevated while release and uptake were near normal.
      Third, several tissues exhibited various transient changes in activity. These
      types of post-lesion change might contribute to altered auditory functions, which
      often accompany hearing loss.

PMID- 10962180
TI  - Diversity and plasticity in amino acid receptor subunits in the rat auditory
      brain stem.
AB  - Glutamate, gamma aminobutyric acid (GABA) and glycine receptors have different
      properties depending on the specific subunit combination utilized. The subunit
      composition of amino acid receptors may help to shape the responses of neurons
      and can provide a diversity of response properties in different neuronal types
      and regions. This allows a synaptic fine tuning for an optimization of processing
      requirements and may also allow for changes in response to changes in input. This
      article reviews the diversity that has been found in the subunit composition of
      GABA, glycine, alpha amino-3-hydroxy-5-methyl-4 isoxazole propionic acid and N
      Methyl, D-aspartate (NMDA) receptors in the mammalian auditory brain stem and
      provides new data on how the NMDAR1 glutamate receptor subunit changes as a
      consequence of deafness. In the latter study, quantitative in situ hybridization
      was used to assess NMDAR1 mRNA expression in six cell types of the rat cochlear
      nucleus. A unilateral cochlear ablation was performed and expression determined
      in the ipsilateral and contralateral cochlear nucleus 5 and 20 days later.
      Significantly decreased expression, compared to normal, was found 5 days
      following deafness, in ipsilateral spherical bushy cells, octopus cells and shell
      neurons, but not in fusiform cells, corn cells or granule cells. At 20 days the
      expression was not significantly different from normal in any of the six cell
      types.

PMID- 10962181
TI  - Central nervous system plasticity during hair cell loss and regeneration.
AB  - Following cochlear ablation, auditory neurons in the central nervous system (CNS)
      undergo alterations in morphology and function, including neuronal cell death.
      The trigger for these CNS changes is the abrupt cessation of afferent input via
      eighth nerve fiber activity. Gentamicin can cause ototoxic damage to cochlear
      hair cells responsible for high frequency hearing, which seems likely to cause a
      frequency-specific loss of input into the CNS. In birds, these hair cells can
      regenerate, presumably restoring input into the CNS. This review summarizes
      current knowledge of how CNS auditory neurons respond to this transient,
      frequency-specific loss of cochlear function. A single systemic injection of a
      high dose of gentamicin results in the complete loss of high frequency hair cells
      by 5 days, followed by the regeneration of new hair cells. Both hair cell
      specific functional measures and estimates of CNS afferent activity suggest that
      newly regenerated hair cells restore afferent input to brainstem auditory
      neurons. Frequency-specific neuronal cell death and shrinkage occur following
      gentamicin damage to hair cells, with an unexpected recovery of neuronal cell
      number at longer survival times. A newly-developed method for topical, unilateral
      gentamicin application will allow future studies to compare neuronal changes
      within a given animal.

PMID- 10962182
TI  - The effects of congenital deafness on auditory nerve synapses and globular bushy
      cells in cats.
AB  - It is well known that auditory deprivation affects the structure and function of
      the central nervous system. Congenital deafness represents one form of
      deprivation, and in the adult white cat, it has been shown to have a clear effect
      upon the synaptic interface between endbulbs of Held and spherical bushy cells.
      It is not known, however, whether all primary synapses are affected and/or
      whether they are affected in the same way and to the same extent. Thus, we
      studied a second neuronal circuit in the deaf white cat involving modified
      (small) endbulbs and globular bushy cells. Compared to normal hearing cats,
      modified endbulbs of congenitally deaf cats were 52.2% smaller but unchanged in
      structural complexity. There was also a striking loss of extracellular space
      between ending and cell body. The somata of postsynaptic globular bushy cells
      were 13.4% smaller and had enlarged postsynaptic densities. These data reveal
      that axosomatic synapses demonstrate abnormal structure as a consequence of
      deafness and that the extent of the abnormalities can vary with respect to the
      circuits involved. The implication of these observations is that synaptic
      anomalies would introduce differential delays within separate circuits, thereby
      desynchronizing neural activity from sound stimuli. This loss of synchronization
      could in turn disrupt temporal processing and compromise a host of related
      functions, including language comprehension.

PMID- 10962183
TI  - Effects of chronic salicylate on GABAergic activity in rat inferior colliculus.
AB  - It is well accepted that salicylate ototoxicity results in reversible tinnitus in
      humans. Salicylate-induced tinnitus may be an example of plasticity of the
      central auditory system and could potentially serve as a model to further
      understand mechanisms of tinnitus generation. This study examined levels of
      glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A)
      receptor in auditory brainstem structures of Long-Evans rats chronically treated
      with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation
      of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects.
      This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol
      saturation analysis was indicative of a salicylate-related increase in receptor
      affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a
      significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in
      the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of
      IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also
      significantly (P<0.05) decreased. These changes were observed only in central
      auditory structures. This suggests that GAD expression and GABA(A) receptor
      binding characteristics may be altered with chronic exposure to sodium salicylate
      and these changes may represent aberrant plasticity clinically experienced as
      tinnitus.

PMID- 10962184
TI  - Down-regulation of inhibition following unilateral deafening.
AB  - Physiological and neurochemical experiments described here suggest that
      unilateral deafening causes a reduction in inhibition in the adult gerbil
      inferior colliculus (IC) contralateral to the deafened ear. Multiple-unit
      recordings were made from single electrode penetrations in the IC prior to and
      directly after contralateral cochlear ablation. These recordings showed up to 60%
      increases in the proportion of sampled loci at which neural activity excited by
      ipsilateral stimulation was observed after the ablation. Novel excitatory
      responses were evident within minutes of the ablation. Western blotting for
      glutamic acid decarboxylase protein levels showed significant decreases in the IC
      contralateral to cochlear ablation, relative to those in the ipsilateral IC, at
      24 h and 7 days survival after the ablation. Four hour or 1 year survival post
      ablation did not produce significant contralateral/ipsilateral differences in
      relation to the control group. Taken together, these results suggest the presence
      of at least two, short-term mechanisms involved in the central response to
      cochlear removal, both of which appear to implicate a decreased inhibitory
      influence. One is a very rapid, stimulus-related, functional unmasking. The other
      is a more delayed reduction in the capacity of gamma-aminobutyric acid synthesis
      in the IC.

PMID- 10962185
TI  - Injury-induced reorganization in adult auditory cortex and its perceptual
      consequences.
AB  - Restricted cochlear lesions in adult animals result in a reorganization of
      auditory cortex such that the cortical region deprived of its normal input by the
      lesion is occupied by expanded representations of adjacent cochlear loci, and
      thus of the frequencies represented at those loci. Analogous injury-induced
      reorganization is seen in somatosensory, visual and motor cortices of adult
      animals after restricted peripheral lesions. The occurrence of such
      reorganization in a wide range of species (including simian primates), and across
      different sensory systems and forms of peripheral lesion, suggests that it would
      also occur in humans with similar lesions. Direct evidence in support of this
      suggestion is provided by a small body of functional imaging evidence in the
      somatosensory and auditory systems. Although such reorganization does not seem to
      have a compensatory function, such a profound change in the pattern of cortical
      activation produced by stimuli exciting peri-lesion parts of the receptor
      epithelium would be expected to have perceptual consequences. However, there is
      only limited psychophysical evidence for perceptual effects that might be
      attributable to injury-induced cortical reorganization, and very little direct
      evidence for the correlation between the perceptual phenomena and the occurrence
      of reorganization.

PMID- 10962186
TI  - Acute spiral ganglion lesions change the tuning and tonotopic organization of cat
      inferior colliculus neurons.
AB  - Many studies have reported plastic changes in central auditory frequency
      organization after chronic cochlear lesions. These studies employed mechanical,
      acoustic or drug-induced disruptions of restricted regions of the organ of Corti
      that permanently alter its tuning and sensitivity and require an extended
      recovery period before central effects can be measured. In this study, mechanical
      lesions were made to 1 mm sectors of the spiral ganglion (SG). These lesions
      remove a restricted portion of the cochlear output, but leave the organ of Corti
      and basilar membrane intact. Multiunit mapping assessed the pre- and post-lesion
      tonotopic organization of the inferior colliculus (IC). Immediately after SG
      lesions, IC neurons previously tuned to the lesion frequencies became less
      sensitive to those frequencies but more sensitive to lesion edge frequencies,
      resulting in a shift in their characteristic frequencies (CFs). Notches in the
      excitatory response areas at frequencies corresponding to the lesion frequencies
      and expansion of spatial tuning curves were also observed. CFs of neurons tuned
      to unlesioned frequencies were unchanged. These results suggest that 'plastic'
      changes similar to those observed after long survival times in previous studies
      require little or no experience and occur within minutes to hours following the
      lesion.

PMID- 10962187
TI  - Plasticity in central representations in the inferior colliculus induced by
      chronic single- vs. two-channel electrical stimulation by a cochlear implant
      after neonatal deafness.
AB  - The goal of this research is to examine the functional consequences of patterned
      electrical stimulation delivered by a cochlear implant in the deafened developing
      auditory system. In previous electrophysiological experiments conducted in the
      inferior colliculus (IC), we have demonstrated that the precise cochleotopic
      organization of the central nucleus (ICC) develops normally in neonatally
      deafened unstimulated cats and is unaltered despite the lack of normal auditory
      input during development. However, these studies also showed that chronic
      electrical stimulation delivered at a single intracochlear location by one
      bipolar channel of a cochlear implant induces significant expansion of the
      central representation of the stimulated cochlear sector and degrades the
      cochleotopic organization of the IC. This report presents additional data from a
      new experimental series of neonatally deafened cats that received chronic
      stimulation on two adjacent bipolar intracochlear channels of a cochlear implant.
      Results suggest that competing inputs elicited by electrical stimulation
      delivered by two adjacent channels can maintain the selective representations of
      each activated cochlear sector within the central auditory system and prevent the
      expansion seen after single-channel stimulation. Alternating stimulation of two
      channels and use of highly controlled electrical signals may be particularly
      effective in maintaining or even sharpening selectivity of central
      representations of stimulated cochlear sectors. In contrast, simultaneous
      stimulation using two channels of a model analog cochlear implant processor in
      one experimental animal failed to maintain channel selectivity and resulted in
      marked expansion and fusion of the central representations of the stimulated
      channels. This potentially important preliminary result suggests that under some
      conditions the central auditory system may be unable to discriminate
      simultaneous, overlapping inputs from adjacent cochlear implant channels as
      distinct.

PMID- 10962188
TI  - Changes in cochlear electrical stimulation induced Fos expression in the rat
      inferior colliculus following deafness.
AB  - Fos immunoreactive (IR) staining was used to examine changes in excitatory
      neuronal activity in the rat inferior colliculus (IC) between normal hearing and
      21 day deaf rats evoked by basal or apical monopolar cochlear electrical
      stimulation. The location of evoked Fos IR neurons was consistent with expected
      tonotopic areas. The number of Fos IR cells increased as stimulation intensity
      increased in both normal and 21 day deaf animals. Stimulation at 1. 5x threshold
      evoked fewer Fos IR cells in 21 day deafened animals compared to normal hearing
      animals. At 5x and above, however, significantly increased numbers of Fos IR
      neurons (in a larger grouping) were evoked in 21 day deafened animals compared to
      normal hearing animals. Another group of animals had 7 days of deafness followed
      by 14 days of chronic basal cochlear electrical stimulation. In this group basal
      monopolar stimulation at 5x evoked not only a greater number of Fos IR neurons,
      compared to normal hearing animals, but the location of their grouping was
      slightly shifted to a more dorso-lateral region in the contralateral IC, compared
      to the normal hearing and 21 day deaf groups. These observations indicate that
      both deafness and chronic electrical stimulation may alter central auditory
      processing.

PMID- 10962189
TI  - GAD levels and muscimol binding in rat inferior colliculus following acoustic
      trauma.
AB  - Pharmacological studies of the inferior colliculus (IC) suggest that the
      inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) plays an
      important role in shaping responses to simple and complex acoustic stimuli.
      Several models of auditory dysfunction, including age-related hearing loss,
      tinnitus, and peripheral deafferentation, suggest an alteration of normal GABA
      neurotransmission in central auditory pathways. The present study attempts to
      further characterize noise-induced changes in GABA markers in the IC. Four groups
      (unexposed control, 0 h post-exposure, 42 h post-exposure, and 30 days post
      exposure) of 3-month-old male Fischer 344 rats were exposed to a high intensity
      sound (12 kHz, 106 dB) for 10 h. Observed hair cell damage was primarily confined
      to the basal half of the cochlea. There was a significant decrease in glutamic
      acid decarboxylase (GAD(65)) immunoreactivity in the IC membrane fraction
      compared to controls (P<0.05) at 0 h (-41%) and 42 h (-28%) post-exposure, with
      complete recovery by 30 days post-exposure (P>0.98). Observed decreases in
      cytosolic levels of GAD(65) were not significant. Quantitative muscimol receptor
      binding revealed a significant increase (+20%) in IC 30 days after sound exposure
      (P<0.05). These data suggest that changes in GABA neurotransmission occur in the
      IC of animals exposed to intense sound. Additional studies are needed to
      determine whether these changes are a result of protective/compensatory
      mechanisms or merely peripheral differentiation, as well as whether these changes
      preserve or diminish central auditory system function.

PMID- 10962190
TI  - Auditory plasticity and hyperactivity following cochlear damage.
AB  - This paper will review some of the functional changes that occur in the central
      auditory pathway after the cochlea is damaged by acoustic overstimulation or by
      carboplatin, an ototoxic drug that selectively destroys inner hair cells (IHCs)
      in the chinchilla. Acoustic trauma typically impairs the sensitivity and tuning
      of auditory nerve fibers and reduces the neural output of the cochlea.
      Surprisingly, our results show that restricted cochlear damage enhances neural
      activity in the central auditory pathway. Despite a reduction in the auditory
      nerve compound action potential (CAP), the local field potential from the
      inferior colliculus (IC) increases at a faster than normal rate and its maximum
      amplitude is enhanced at frequencies below the region of hearing loss. To
      determine if this enhancement was due to loss of sideband inhibition, we recorded
      from single neurons in the IC and dorsal cochlear nucleus before and after
      presenting a traumatizing above the unit's characteristic frequency (CF).
      Following the exposure, some neurons showed substantial broadening of tuning
      below CF, less inhibition, and a significant increase in discharge rate,
      consistent with a model involving loss of sideband inhibition. The central
      auditory system of the chinchilla can be deprived of some of its cochlear inputs
      by selectively destroying IHCs with carboplatin. Selective IHC loss reduces the
      amplitude of the CAP without affecting the threshold and tuning of the remaining
      auditory nerve fibers. Although the output of the cochlea is reduced in
      proportion to the amount of IHC loss, the IC response shows only a modest
      amplitude reduction, and remarkably, the response of the auditory cortex is
      enhanced. These results suggest that the gain of the central auditory pathway can
      be up- or down regulated to compensate for the amount of neural activity from the
      cochlea.

PMID- 10962191
TI  - Neural plasticity in the mouse inferior colliculus: relationship to hearing loss,
      augmented acoustic stimulation, and prepulse inhibition.
AB  - C57BL/6J (C57) and DBA/2J (DBA) mice exhibit progressive high-frequency hearing
      loss. Extracellular recordings of responses of neurons in the inferior colliculus
      (IC) evoked by 70-dB SPL tones indicated that normal tonotopic organization was
      greatly disrupted in both strains: still-audible lower frequencies (4-12 kHz)
      evoked responses in a large percentage of recording sites in ventral tonotopic
      regions that normally respond strongly to high frequencies only. To relate the IC
      responses to an auditory behavior, prepulse inhibition (PPI) was measured using
      70-dB tones as prepulses. As high-frequency hearing loss progressed in C57 mice,
      prepulses of 4-12 kHz elicited stronger PPI, and this was significantly
      correlated with changes in the percentage of IC recording sites responding to 70
      dB tones (the neural pathway for PPI includes the IC). The analysis was extended
      to DBA mice that had been exposed to an augmented acoustic environment (AAE) - a
      procedure that improves PPI. In these mice, a higher percentage of IC recording
      sites responded to 70-dB tones, and this was correlated with improved PPI. The
      data suggest that responses of IC neurons reflect both hearing loss-induced
      plasticity and changes induced by exposure to an AAE, and these neural changes
      are correlated with the magnitude of PPI.

PMID- 10962192
TI  - Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after
      intense sound exposure.
AB  - Increases in multiunit spontaneous activity (hyperactivity) can be induced in the
      dorsal cochlear nucleus (DCN) by intense sound exposure. This hyperactivity has
      been observed in the hamster and rat following exposure to a 10 kHz tone at a
      level of 125-130 dB SPL for a period of 4 h. The present study demonstrates that
      the onset of this hyperactivity is not immediate, but develops in the DCN between
      2 and 5 days after exposure. Mean rates of multiunit spontaneous activity
      increased sharply from below normal levels at day 2 to higher than normal levels
      at day 5. The mean magnitude of activity continued to increase more gradually
      over the next 6 months. During this period, changes in the distribution of
      hyperactivity across the tonotopic array were also noted. The hyperactivity was
      more broadly distributed across the DCN at the early post-exposure times (5 and
      14 days) than at later post-exposure recovery times (30 and 180 days), and peak
      activity was found at increasingly more medial positions over this time frame.
      These changes over time indicate that the mechanisms leading to hyperactivity
      following intense sound exposure are more complex than previously realized.

PMID- 10962193
TI  - Differential display and gene arrays to examine auditory plasticity.
AB  - Differential gene expression forms the basis for development, differentiation,
      regeneration, and plasticity of tissues and organs. We describe two methods to
      identify differentially expressed genes. Differential display, a PCR-based
      approach, compares the expression of subsets of genes under two or more
      conditions. Gene arrays, or DNA microarrays, contain cDNAs from both known genes
      and novel genes spotted on a solid support (nylon membranes or glass slides).
      Hybridization of the arrays with RNA isolated from two different experimental
      conditions allows the simultaneous analysis of large numbers of genes, from
      hundreds to thousands to whole genomes. Using differential display to examine
      differential gene expression after noise trauma in the chick basilar papilla, we
      identified the UBE3B gene that encodes a new member of the E3 ubiquitin ligase
      family (UBE3B). UBE3B is highly expressed immediately after noise in the lesion,
      but not in the undamaged ends, of the chick basilar papilla. UBE3B is most
      similar to a ubiquitin ligase gene from Caenorhabditis elegans, suggesting that
      this gene has been conserved throughout evolution. We also describe preliminary
      experiments to profile gene expression in the cochlea and brain with commercially
      available low density gene arrays on nylon membranes and discuss potential
      applications of this and DNA microarray technology to the auditory system.

PMID- 10962194
TI  - Effects of a single day of feed restriction on changes in serum leptin,
      gonadotropins, prolactin, and metabolites in aged and young mares.
AB  - In a variety of species, short-term feed restriction leads to rapid changes in
      the reproductive axis and reduces serum levels of leptin. Two experiments were
      performed to test the hypothesis that a single day of feed restriction in aged
      and young mares would cause a suppression of the gonadotropins and serum leptin
      concentrations. The estrous cycles of 12 aged (>eight years; Exp. 1) and eight
      young (<five years; Exp. 2) mares were synchronized and the mares were
      conditioned to twice-daily meal feeding. On the seventh day after
      synchronization, restricted mares (n = 6 for Exp. 1; n = 4 for Exp. 2) were not
      fed for 24 hr; all mares were fed the second day. In Exp. 1, serum leptin
      concentrations significantly decreased in restricted mares, but not in controls.
      In Exp. 2, serum leptin concentrations declined in restricted mares and no
      decline was seen in the controls. Serum glucose concentrations did not change in
      response to feed restriction or refeeding, but in both experiments feed
      restriction caused an increase in free fatty acids. For both experiments,
      prolactin, FSH, and LH serum concentrations were not significantly altered by
      feed restriction. The observed absence of suppression may reflect the maintenance
      of sufficient levels of metabolizable fuels, rather than a failure of leptin to
      signal nutritional status to the reproductive axis of the mare.

PMID- 10962195
TI  - Supplemental triiodothyronine, feeding regimens, and metabolic responses by the
      broiler chicken.
AB  - There are conflicting results concerning the role of the thyroid hormones in
      lipid metabolism. The experiments in this report were designed to examine the
      role of T(3) in modifying responses obtained by shifting birds from moderate to
      low protein diets. Birds were grown from 7 to 28 d on a diet containing 18%
      protein. At this time, birds were switched to a diet containing 12% protein +/-
      T(3) The switch was accomplished either immediately or after a 24 hr fast.
      Measurements taken included in vitro lipogenesis (IVL), hepatic enzyme activities
      and plasma metabolites and thyroid hormones. Simply switching to birds to the low
      protein diet increased IVL, but rates were similar for three days following the
      switch. Feeding T(3) in this same regimen resulted in lower, but again, constant
      rates of IVL. In contrast, although switching protein levels after a 24 hr fast
      increased IVL, the rate after two days of refeeding was nearly double that
      following one day. This accentuated response was somewhat attenuated by including
      T(3) in the diet. Neither fasting nor refeeding altered plasma T(3) relative to
      ad libitum values. Supplemental dietary T(3) increased plasma T(3) and results
      were not affected by feeding regimens. Plasma T(4) was greatest in birds fasted
      for 24 hr and least in birds fed T(3) suggesting that feeding regimens may
      regulate the conversion of T(4) to T(3) It is suggested from this study that some
      of the effects of alterations in dietary feeding regimens can be modulated by
      T(3)

PMID- 10962196
TI  - Porcine erythropoietin receptor: molecular cloning and expression in embryonic
      and fetal liver.
AB  - The full coding sequence for porcine erythropoietin receptor (EPOR) was
      elucidated using reverse transcription polymerase chain reaction (PCR) (rtPCR)
      and 3' and 5' rapid amplification of cDNA ends (RACE) procedures. Total RNA
      collected from Day 30 fetal liver was used as starting material. A 1843 bp
      sequence was obtained from which could be inferred a 509 amino acid protein which
      was 79-85% identical to the amino acid sequence of erythropoietin receptor from
      other species. Total RNA samples collected from white crossbred intact, white
      crossbred UHO and Meishan gilts on Days 24, 30 and 40 of gestation were subjected
      to Northern blotting using porcine EPOR cDNA as probe. Results indicated that (1)
      a major and two minor forms of mRNA are present, (2) fetal liver mRNA
      concentrations for EPOR are low on Day 24 of gestation and increase dramatically
      by Day 30 and (3) mRNA concentrations for EPOR tended to be decreased by
      intrauterine crowding.

PMID- 10962197
TI  - Postnatal function of the somatotrophic axis in pigs born naturally or by
      Caesarian section.
AB  - This study was designed to determine what effects the birth process would have on
      development of the somatotrophic axis in neonatal pigs. Eight crossbred sows were
      selected (n = 4 natural birth and n = 4 Caesarian section) for the present study.
      Blood and tissue samples from 38 pigs were collected at birth. Twenty pigs were
      maintained with natural birth sows until sacrificed for blood and tissue
      collection at 2 wk of age. Gestational age at birth did not differ (P > 0.16)
      between natural birth and C-section pigs. Average daily gain (ADG) from birth
      until 2 wk of age was reduced (P < 0.0001) by 39.3% in the C-section pigs as
      compared to the natural birth pigs. Serum growth hormone (GH) did not differ (P >
      0.86) at birth, but was greater (P < 0.024) at 2 wk in C-section pigs. Serum
      insulin-like growth factor 1 (IGF-1) was greater at birth (P < 0. 0025) and at 2
      wk of age (P < 0.035) in the natural birth pigs. Serum concentration of IGF-2 did
      not differ at birth (P > 0.8) but was greater (P < 0.043) in natural birth pigs
      at 2 wk of age. Pituitary content of GH mRNA and GH-releasing hormone receptor
      mRNA did not differ (P > 0.90) between groups regardless of age; however,
      expression of both mRNAs declined (P < 0.0003) from birth until 2 wk of age.
      There tended to be a birth type X age interaction (P < 0. 082) for liver IGF-1
      mRNA such that C-section pigs had a greater expression at 2 wk of age. Liver IGF
      1 mRNA expression increased (P < 0.0001) in both groups from birth to 2 wk of
      age. Liver expression of GH receptor mRNA was greater in C-section pigs at birth
      (P < 0. 04) and 2 wk of age (P < 0.03). These data provide evidence that the
      natural birth process affects postnatal development and/or function of the
      somatotrophic axis in the neonatal pig.

PMID- 10962198
TI  - Long form leptin receptor mRNA expression in the brain, pituitary, and other
      tissues in the pig.
AB  - Much effort has focused recently on understanding the role of leptin, the obese
      gene product secreted by adipocytes, in regulating growth and reproduction in
      rodents, humans and domestic animals. We previously demonstrated that leptin
      inhibited feed intake and stimulated growth hormone (GH) and luteinizing hormone
      (LH) secretion in the pig. This study was conducted to determine the location of
      long form leptin receptor (Ob-Rl) mRNA in various tissues of the pig. The leptin
      receptor has several splice variants in the human and mouse, but Ob-Rl is the
      major form capable of signal transduction. The Ob-Rl is expressed primarily in
      the hypothalamus of the human and rodents, but has been located in other tissues
      as well. In the present study, a partial porcine Ob-Rl cDNA, cloned in our
      laboratory and specific to the intracellular domain, was used to evaluate the Ob
      Rl mRNA expression by RT-PCR in the brain and other tissues in three 105 d-old
      prepuberal gilts and in a 50 d-old fetus. In 105 d-old gilts, Ob-Rl mRNA was
      expressed in the hypothalamus, cerebral cortex, amygdala, thalamus, cerebellum,
      area postrema and anterior pituitary. In addition, Ob-Rl mRNA was expressed in
      ovary, uterine body, liver, kidney, pancreas, adrenal gland, heart, spleen, lung,
      intestine, bone marrow, muscle and adipose tissue. However, expression was absent
      in the thyroid, thymus, superior vena cava, aorta, spinal cord, uterine horn and
      oviduct. In the 50 d-old fetus, Ob-Rl mRNA was expressed in brain, intestine,
      muscle, fat, heart, liver and umbilical cord. These results support the idea that
      leptin might play a role in regulating numerous physiological functions.

PMID- 10962199
TI  - Vitamin A deficiency causes oxidative damage to liver mitochondria in rats.
AB  - Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was
      studied using three different groups of rats: (i) control rats, (ii) rats fed a
      vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re
      fed a control diet for 30 d. No statistical difference in body weight and food
      intake was found between control and vitamin A-deficient rats. Liver GSH
      concentration was similar in both groups. However, in vitamin A-deficient rats,
      the mitochondrial GSH/GSSG ratio was significantly lower and the levels of
      malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were
      higher when compared to control rats. These values were partially restored in re
      fed rats. The mitochondrial membrane potential of vitamin A-deficient rats was
      significantly lower than in control rats and returned to normal levels in
      restored vitamin A rats. Two populations of mitochondria were found in vitamin A
      deficient rats according to the composition of membrane lipids. One population
      showed a similar pattern to the control mitochondria and the second population
      had a higher membrane lipid content. This report emphasizes the protective role
      of vitamin A in liver mitochondria under physiological circumstances.

PMID- 10962200
TI  - Time-dependent inhibition of immune complex-induced lung injury by catalase:
      relationship to alterations in macrophage and neutrophil matrix metalloproteinase
      elaboration.
AB  - Rats were subjected to acute lung injury by the intra-alveolar formation of IgG
      immune complexes of bovine serum albumin (BSA) and anti-BSA. In this model of
      injury, complement activation occurs and large numbers of neutrophils invade the
      interstitium and alveolar space. In the present study, animals were treated with
      intratracheal catalase concomitantly with anti-BSA or after a lag period of 5-120
      min. Catalase treatment at time-zero or at 5 min post injury failed to prevent
      lung injury as indicated by permeability change, histological features, and
      neutrophil influx. However, treatment after a delay of 15-30 min (but not 120
      min) afforded substantial protection. Consistent with past findings [19], lung
      injury was accompanied by an accumulation of matrix metalloproteinase 9 (MMP-9)
      in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between
      inhibition of injury and reduction in MMP-9 levels. In vitro studies conducted in
      parallel revealed that unstimulated alveolar macrophages did not produce
      measurable MMP-9, while there was a large induction following exposure to the
      same immune complexes that initiated injury in vivo. MMP-2 was also slightly
      upregulated under the same conditions. Concomitant treatment with catalase
      greatly inhibited MMP-9 production by macrophages in response to immune
      complexes, but this treatment had little effect on basal production of either MMP
      9 or MMP-2 by macrophage. The same concentration of catalase that suppressed MMP
      9 elaboration also inhibited the production of tumor necrosis factor alpha. In
      contrast, when neutrophils were treated with catalase and then exposed to immune
      complexes, the antioxidant failed to prevent the release of either MMP-2 or MMP
      9. Taken together, these findings demonstrate that antioxidant treatment
      interferes with elaboration of MMPs by alveolar macrophages. Protection against
      lung injury is correlated with reduction in MMP levels in the BAL fluid.

PMID- 10962202
TI  - Reactions of e(-)(aq), CO(2)(*)(-), HO(*), O(2)(*)(-) and O(2)((1)delta(g)) with
      a dendro[60]fullerene and C(60)[C(COOH)(2)](n) (n = 2-6).
AB  - Using pulse radiolysis and laser flash photolysis, we have investigated the
      reactions of the deleterious species, e(-)(aq), HO&z.rad;, O(2)(*)(-) and
      O(2)((1)Delta(g)) with 10 water-soluble cyclopropyl-fused C(60) derivatives
      including a mono-adduct dendro[60]fullerene (d) and C(60) derivatives based on
      C(60)[C(COOH)(2)](n=2-6), some of which are known to be neuroprotective in vivo.
      The rate constants for reactions of e(-)(aq) and HO&z.rad; lie in the range 0.5
      3.3 x 10(10) M(-1) s(-1). The d and bis-adduct monoanion radicals display sharp
      absorption peaks around 1000 nm (epsilon = 7 000-11 500 M(-1) cm(-1)); the anions
      of the tris-, tetra-, and penta-adduct derivatives have broader, weaker
      absorptions. The monohydroxylated radicals have their most intense absorption
      maxima around 390-440 nm (epsilon = 1000-3000 M(-1) cm(-1)). The anion and
      hydroxylated radical absorption spectra display a blue-shift as the number of
      addends increases. The radical anions react with oxygen (k approximately 10(7)
      10(9) M(-1) s(-1)). The reaction of O(2)(*)(-) with the C(60) derivatives does
      not occur via an electron transfer. The rate constants for singlet oxygen
      reaction with the dendrofullerene and eee-derivative in D(2)O at pH 7.4 are k
      approximately 7 x 10(7) and approximately 2 x 10(7) M(-1) s(-1) respectively, in
      contrast to approximately 1.2 x 10(5) M(-1) s(-1) for the reaction with C(60) in
      C(6)D(6). The large acceleration of the rates for electron reduction and singlet
      oxygen reactions in water is due to a solvophobic process.

PMID- 10962201
TI  - Induction of aldose reductase in cultured human microvascular endothelial cells
      by advanced glycation end products.
AB  - Accelerated formation and accumulation of advanced glycation end products, as
      well as increased flux of glucose through polyol pathway, have been implicated in
      the pathogenesis of diabetic vascular complications. We investigated effects of
      advanced glycation end products on the levels of aldose reductase mRNA, protein,
      and activity in human microvascular endothelial cells. When endothelial cells
      were cultured with highly glycated bovine serum albumin, aldose reductase mRNA in
      endothelial cells demonstrated concentration-dependent elevation. The increase in
      aldose reductase mRNA was accompanied by elevated protein expression and enzyme
      activity. Significant increase in the enzyme expression was also observed when
      endothelial cells were cultured with serum obtained from diabetic patients with
      end-stage renal disease. Pretreatment of the endothelial cells with probucol or
      vitamin E prevented the advanced glycation end products-induced increases in
      aldose reductase mRNA and protein. Electrophoretic mobility shift assays using
      the nuclear extracts of the endothelial cells treated with advanced glycation end
      products showed enhancement of specific DNA binding activity for AP-1 consensus
      sequence. These results indicate that accelerated formation of advanced glycation
      end products in vivo may elicit activation of the polyol pathway, possibly via
      augmented oxidative stress, and amplify endothelial cell damage leading to
      diabetic microvascular dysfunction.

PMID- 10962203
TI  - Lecithinized copper, zinc-superoxide dismutase ameliorates prolonged hypoxia
      induced injury of cardiomyocytes.
AB  - Recent studies have suggested that prolonged hypoxia results in increased
      production of reactive oxygen species in cardiomyocytes, which leads to apoptosis
      of these cells. We previously showed that lecithinized recombinant human copper,
      zinc-superoxide dismutase (rhSOD) showed increased bioavailability through
      greater membrane affinity and a longer half-life than unmodified SOD. The purpose
      of this study was to investigate whether lecithinized SOD plays a protective role
      against hypoxic injury in cardiomyocytes. Cultured rat cardiomyocytes incubated
      with lecithinized SOD (100 U/ml), unmodified SOD (100 U/ml), or vehicle alone
      were subjected to hypoxia for up to 72 h. Lecithinized SOD, but not unmodified
      SOD, was successfully delivered intracellularly, which was verified by Western
      blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized
      SOD significantly suppressed hypoxia-induced cell damage. Since lecithinized SOD
      also suppressed hypoxia-induced DNA fragmentation, the improved cell survival
      provided by lecithinized SOD is thought to be mediated by its antiapoptotic
      effect. In summary, lecithinization resulted in a facilitated rhSOD delivery into
      cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to
      prolonged hypoxia.

PMID- 10962204
TI  - Polynitroxyl-albumin (PNA) plus tempol attenuate lung capillary leak elicited by
      prolonged intestinal ischemia and reperfusion(1).
AB  - Stable nitroxyl radicals (nitroxides) are potential antioxidant drugs, and we
      have previously reported that linking nitroxide to biological macromolecules can
      improve therapeutic activity in at least two ways. First, polynitroxylated
      compounds such as polynitroxyl human serum albumin (PNA) are a novel class of
      high molecular weight, extracellular antioxidants. Second, compounds such as PNA
      can prolong the half-life of free (unbound, low molecular weight) nitroxides such
      as 4-hydroxy-2,2,6, 6-tetramethylpiperidine-N-oxyl (Tempol) in vivo. Unlike PNA,
      Tempol can readily access the intracellular compartment. Thus PNA can act alone
      in the extracellular compartment, or in concert with Tempol, to provide
      additional antioxidant protection within cells. In this study, we compared the
      abilities of PNA, Tempol, and the combination of PNA + Tempol to prevent lung
      microvascular injury secondary to prolonged gut ischemia (I, 120 min) and
      reperfusion (R, 20 min) in the rat. Pulmonary capillary filtration coefficient
      (K(f,c)) and lung neutrophil retention (tissue myeloperoxidase activity, MPO)
      were measured in normal, isolated rat lungs perfused with blood harvested from
      I/R rats. Blood donor rats were treated with drug during ischemia. Gut I/R
      resulted in a marked increase in pulmonary capillary coefficient and lung MPO.
      PNA + Tempol, but not PNA alone or Tempol alone, at the doses used, prevented the
      development of lung leak. None of the treatments had an effect on lung neutrophil
      retention. Anti-inflammatory therapeutic activity appeared to correlate with
      blood Tempol level: in the presence of PNA, blood Tempol levels were maintained
      in the 50-100 microM range vs. essentially undetectable levels shortly after
      Tempol was administered alone. In this model of lung injury secondary to
      prolonged gut I/R, lung capillary leak was prevented when the membrane-permeable
      compound Tempol was maintained in its active, free radical state by PNA.

PMID- 10962205
TI  - Incorporation of the elderberry anthocyanins by endothelial cells increases
      protection against oxidative stress.
AB  - The objective of this study was to investigate the ability of endothelial cells
      (EC) to incorporate anthocyanins and to examine their potential benefits against
      various oxidative stressors. Endothelial dysfunction has been proposed to play an
      important role in the initiation and development of vascular disease, with
      studies having shown that administration of antioxidants improves endothelial
      function. Elderberry extract contains 4 anthocyanins, which where incorporated
      into the plasma membrane and cytosol of EC following 4 h incubation at 1 mg.ml(
      1). However, incorporation within the cytosol was considerably less than that in
      the membrane. Uptake within both regions appeared to be structure dependent, with
      monoglycoside concentrations higher than that of the diglucosides in both
      compartments. The enrichment of EC with elderberry anthocyanins conferred
      significant protective effects in EC against the following oxidative stressors:
      hydrogen peroxide (H(2)O(2)); 2, 2'-azobis(2-amidinopropane) dihydrochloride
      (AAPH); and FeSO(4)/ascorbic acid (AA). These results show for the first time
      that vascular EC can incorporate anthocyanins into the membrane and cytosol,
      conferring significant protective effects against oxidative insult. These
      findings may have important implications on preserving EC function and preventing
      the initiation of EC changes associated with vascular diseases.

PMID- 10962206
TI  - Role of paxillin in metabolic oxidative stress-induced cytoskeletal
      reorganization: involvement of SAPK signal transduction pathway and PTP-PEST gene
      expression.
AB  - Previous studies have shown that glucose deprivation-induced cell death is
      associated with apoptosis, which is characterized by cellular membrane blebbing
      in multi-drug-resistant human breast carcinoma MCF-7/ADR cells. In this study, we
      investigated the mechanism of glucose deprivation-induced cytoskeletal
      reorganization, which is known to be responsible for the morphological
      alterations. An increase in the formation of focal adhesion and stress fibers was
      observed during the early period of glucose deprivation (1-2 h). However, a
      disappearance of focal adhesion complexes and a loss of stress fiber formation
      along with membrane blebbing were observed when glucose deprivation continued.
      These alterations were delayed in MCF-7/ADR cells transfected with bcl-2 and
      completely suppressed by treatment with an antioxidant, N-acetyl-L-cysteine.
      These results indicated that glucose deprivation-induced oxidative stress caused
      the cytoskeletal reorganization. The glucose deprivation-induced alteration of
      cytoskeletal organization was further investigated by studying a modification of
      paxillin, one of the focal adhesion proteins. Immunoblotting with anti-paxillin
      antibody showed that the paxillin band shifted from 68 kDa to about 80 kDa during
      1-4 h of glucose deprivation. The mobility shift indicated the modification of
      paxillin. This possibility was further studied by an immunoprecipitation assay
      with anti-paxillin/anti-phosphotyrosine antibody and phosphoamino acid analysis
      (PAA). The immunoprecipitation study revealed that the level of tyrosine
      phosphorylation of paxillin was maintained for 2 h and then markedly decreased
      without a change in the total level of paxillin. The PAA study showed that
      paxillin is dephosphorylated on tyrosine concurrent with phosphorylation on
      serine/threonine. Expression of a dominant-negative mutant of c-Jun NH(2)
      terminal kinase (JNK1) suppressed glucose deprivation-induced JNK1 activation,
      PTP-PEST gene expression, and alteration of paxillin. Taken together, these
      results suggest that the alteration of the phosphorylation/dephosphorylation of
      paxillin may be related to the cytoskeletal reorganization and these events are
      mediated by glucose deprivation-induced oxidative stress and the stress-activated
      protein kinase signal transduction pathway.

PMID- 10962207
TI  - Cat's claw inhibits TNFalpha production and scavenges free radicals: role in
      cytoprotection.
AB  - Cat's claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin
      that is widely used for inflammatory disorders and was previously described as an
      inhibitor of NF-kappaB. Cat's claw was prepared as a decoction (water extraction)
      of micropulverized bark with and without concentration by freeze-drying. Murine
      macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue
      exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH,
      0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by
      lipopolysaccharide (LPS 0.5 microg/ml). Cat's claw was an effective scavenger of
      DPPH; the EC(50) value for freeze-dried concentrates was significantly less than
      micropulverized (18 vs. 150 microg/ml, p <.05). Cat's claw (10 microg/ml freeze
      dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity.
      LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw suppressed
      TNFalpha production by approximately 65-85% (p <.01) but at concentrations
      considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2
      ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an
      effective antioxidant, but perhaps more importantly a remarkably potent inhibitor
      of TNFalpha production. The primary mechanism for cat's claw anti-inflammatory
      actions appears to be immunomodulation via suppression of TNFalpha synthesis.

PMID- 10962208
TI  - Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid.
AB  - Increasing evidence indicates that oxidative modification of low-density
      lipoprotein (LDL) is an important determinant in atherogenesis, and following
      menopause, the incidence of coronary heart disease is as prevalent in women as it
      is in men. Estrogen has been demonstrated to inhibit the susceptibility of LDL to
      be oxidized, and more recently the use of phytoestrogens has been considered for
      estrogen replacement therapy. In this study the antioxidant activity of the three
      major phytoestrogens: genistein, daidzein, and equol were measured in terms of
      LDL oxidative susceptibility. Increasing levels of genistein, daidzein, and equol
      inhibited LDL oxidation, and this inhibitory effect was further enhanced in the
      presence of ascorbic acid. The synergism exhibited by these compounds is of
      clinical importance to phytoestrogen therapy since the efficacy of phytoestrogens
      as effective antioxidants is evident at concentration well within the range found
      in the plasma of subjects consuming soy products. However, this synergism,
      combined with the low reactivity of the phytoestrogens with peroxyl radicals,
      suggests that an antioxidant mechanism other then free radical scavenging
      reactions account for the phytoestrogen antioxidant effect. A structural basis
      for inhibition of LDL oxidation involving interaction of the phytoestrogens with
      apoB-100 is postulated.

PMID- 10962209
TI  - Effects of aging and hyperoxia on oxidative damage to cytochrome c in the
      housefly, Musca domestica.
AB  - Cytochrome c is a component of the mitochondrial electron transport chain, where
      it transfers electrons from ubiquinol-cytochrome c reductase to cytochrome c
      oxidase. Autoxidation of some of the components of the electron transport chain
      is the main source of intracellular O(2)(-*)/H(2)O(2) production in aerobic
      organisms. Because cytochrome c is located on the outer surface of the inner
      mitochondrial membrane, it is likely to be constantly exposed to H(2)O(2),
      secreted by mitochondria into the cytosol. The specific objective of this study
      was to determine whether cytochrome c in the flight muscle mitochondria of the
      housefly is oxidatively damaged during aging and/or under severe oxidative stress
      induced by exposure of flies to 100% oxygen. Results of two independent methods,
      namely tritiated borohydride labeling for determining carbonylation and mass
      spectral analysis for the measurement of molecular mass, indicated that neither
      the carbonyl level nor the molecular mass of cytochrome c was affected by aging
      or hyperoxia. Thus, either cytochrome c is resistant to oxidative damage in vivo
      or the oxidized cytochrome c is promptly degraded. These findings also support
      the concept that protein oxidative damage during aging and under oxidative stress
      is selective.

PMID- 10962210
TI  - Are some idiopathic epilepsies disorders of ion channels?: A working hypothesis.
AB  - Epilepsy is a common neurological disease and encompasses a variety of disorders
      with paroxysms. Although there is a genetic component in the pathogenesis of
      epilepsy, the molecular mechanisms of this syndrome remains poorly understood.
      Linkage analysis and positional cloning have not been sufficient tools for
      determining the pathogenic mechanisms of common idiopathic epilepsies, and hence,
      novel approaches, based on the etiology of epilepsy, are necessary. Recently,
      many paroxysmal disorders, including, epilepsy, have been considered to be due to
      ion channel abnormalities or channelopathies. Results of recent studies employing
      gene analysis in animal models of epilepsy and human familial epilepsies support
      the hypothesis that at least some of the so called idiopathic epilepsies, i.e.
      epilepsies currently, classified as idiopathic could be considered as a
      channelopathy. This hypothesis is consistent with the putative prerequisites for
      genes responsible for the majority of idiopathic epilepsies that can adequately
      explain the following characteristics of epilepsy. Neuronal hyperexcitability,
      dominant inheritance with various penetrance, pharmacological role of some
      conventional antiepileptic drugs, age dependency in the onset of epilepsy, and
      the involvement of genetic factors in the pathogenesis of post-traumatic
      epilepsy. Search for mutations in ion channels expressed in the central nervous
      system may help in finding defects underlying some of idiopathic epilepsies,
      thereby enhancing, our understanding of the molecular pathogenesis of epilepsy. A
      working hypothesis to view certain idiopathic epilepsies as disorders of ion
      channels should provide a new insight to our understanding of epilepsy and allow
      the design of novel therapies.

PMID- 10962211
TI  - Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from
      patients with recent tonic-clonic seizures.
AB  - We have previously reported increased concentrations of interleukin (1L)-6 in CSF
      from patients with tonic-clonic seizures, where increased cytokine production
      most likely is a consequence of neuronal epileptic activity associated with
      seizures. The biological effects of IL-6 are mediated by other cytokines, which
      are studied here in addition to IL-6. The purpose of this study was to analyze
      levels of soluble cytokines from plasma and CSF from patients with newly
      developed tonic-clonic seizures. The concentrations of IL-6, IL-1 receptor
      antagonist (IL-1RA), IL-1beta, tumor necrosis factor (TNFalpha) and nerve growth
      factor (NGF) were measured from plasma and CSF from 22 patients with newly
      developed tonic-clonic seizures within 24 h from the seizure and 18 controls. The
      mean concentrations of IL-6 were significantly increased in CSF (P<0.001) and
      plasma (P<0.01) after tonic-clonic seizures, there was some indication of
      increased concentrations of IL-1RA and no significant change in NGF, IL-1beta or
      TNFalpha. Our study shows that cytokine network is activated in patients after
      recent tonic-clonic seizures. We provide evidence of intrathecal production of IL
      6 associated with electrical seizure activity.

PMID- 10962212
TI  - The effect of CGP-40116 on pilocarpine evoked seizures in mice exposed to
      transient episode of brain ischemia.
AB  - The objective of the study was to examine the role of N-methyl-D-aspartate (NMDA)
      receptors in the modulation of a brain tolerance after a transient cerebral
      ischemia. Adult mice were exposed for 30 min to bilateral clamping of common
      carotid arteries (BCCA) under anaesthesia. The competitive NMDA antagonist CGP
      40116 was administered intraperitoneally (i.p.) in two experimental paradigms,
      (a) acute treatment: twice, 4.0 mg/kg; 1.5 h before the clamping of vessels and 6
      h after re-circulation and (b) chronic treatment in a dose of 1.0 mg/kg; started
      24 h after re-circulation and continued once daily for 13 days with the last
      injection 24 h before the induction of convulsions. Seizures were evoked with
      pilocarpine (400 mg/kg, i.p.) 14 days after BCCA. The preliminary study showed
      that BCCA induced protection against pilocarpine toxicity. The acute treatment
      with CGP-40116 partially diminished the anticonvulsant phenomenon. In contrast,
      the chronic treatment with the drug led to a marked potentiation of the effect.
      The whole brain gamma-aminobutyric acid (GABA) analysis performed 14 days after
      BCCA showed a moderate increase in vehicle-treated mice and a significant
      elevation after chronic treatment with CGP-40116. It can be concluded that NMDA
      antagonists may exert the opposite effects on the brain tolerance against
      pilocarpine toxicity after BCCA. The acute treatment with CGP-40116 diminished
      its induction while the chronic low-dose treatment enhanced a brain tolerance,
      possibly through the mechanism of chemical preconditioning.

PMID- 10962213
TI  - The international classification of the epilepsies and epileptic syndromes. An
      algorithm for its use in clinical practice.
AB  - An algorithm has been structured as a guided reading of the international league
      against epilepsy (ILAE) syndromic classification to be used in clinical practice
      by less experienced physicians in newly diagnosed patients. The algorithm
      followed the original structure of the classification, which identifies major
      syndromic groups, subgroups, and specific syndromes. Validation required two
      raters, a resident and a board-certified neurologist, to apply the algorithm with
      different techniques (direct or recorded interview, medical record consultation)
      to 19 children and 18 adults with epilepsy with information available at the time
      of diagnosis. The two raters' diagnoses were compared with those of the caring
      physicians, and cases where disagreement arose were discussed in conference to
      achieve consensus. The kappa statistic was used as a measure of inter-rater
      agreement. Caring physicians and both raters agreed in 51% of cases. Substantial
      agreement (kappa = 0.75) was obtained between the resident and the neurologist on
      major diagnostic groups and subgroups, mostly in adults. Agreement with the
      caring physician was slightly more satisfactory for the resident (kappa=0.67)
      than for the neurologist (kappa = 0.60). Agreement was better with direct or
      indirect interview than with record consultation, and improved further after
      discussion. Agreement was obtained after discussion in 32% of cases, in some of
      which the caring physician agreed on the resident's diagnosis. Agreement was less
      satisfactory for specific syndromes. On this basis, an algorithm of the ILAE
      classification is a fairly reliable instrument only for making a broad syndromic
      classification of epilepsy at the time of diagnosis. The limits of the algorithm
      tend mostly to reflect the intrinsic limitations of the classification itself.

PMID- 10962214
TI  - Behavioral markers for self- and other-attribution of memory: a study in patients
      with temporal lobe epilepsy and healthy volunteers.
AB  - OBJECTIVES: The correlation between clinical measures of memory and subjectively
      reported memory is often poor. Regarding this we investigated in patients with
      temporal lobe epilepsy (TLE) whether there is evidence that persons mistake other
      cognitive performances for memory due to subjective memory theories. METHODS: a
      neuropsychological test battery comprising measures of attention, verbal/figural
      memory and other visual or language related functions was applied in patients
      with left (L-TLE, n=24) or right temporal lobe epilepsy (R-TLE, n=21) and healthy
      volunteers (n=20). In addition, subjective self- and other-reported memories were
      assessed by the subjective memory questionnaire (SMQ). RESULTS: subjective
      measures as well as objective measures indicate significant cognitive impairment
      in TLE and in L-TLE in particular. Self-reports and other-reports are
      interrelated but only self-reported memory correlates significantly with
      objective memory performance. Regression analysis indicates that self-reported
      memory is best predicted by word fluency followed by verbal memory and
      vocabulary, and other-reported memory is best predicted by word fluency,
      vocabulary, confrontation naming, and verbal recognition memory. DISCUSSION: The
      results suggest that attribution of memory refers to a subjective view of memory
      which is wider than its neuropsychological definition. It furthermore differs
      dependent on the observer's point of view. Memory is preferentially concluded
      from verbal behaviors. These reflect language skills and access to vocabulary
      rather than declarative memory. Consideration of subjective memory theories and
      associated attribution processes can significantly contribute to our
      understanding of the often-poor relationship between objective test results and
      subjective impairment in TLE.

PMID- 10962215
TI  - Tiagabine in the treatment of epilepsy--a clinical review with a guide for the
      prescribing physician.
AB  - Tiagabine is currently recommended mainly as add-on therapy in adults and
      children above 12 years with partial epilepsy not satisfactorily controlled with
      other antiepileptic drugs. Based on available evidence and our clinical
      experience, tiagabine should be used preferably in patients sharing one or more
      of the following additional features, (i) a history of drug-induced cutaneous
      adverse events; (ii) mild to moderate epilepsy allowing for a slow titration and
      gradual onset of anticonvulsant action over a few weeks; (iii) patients for whom
      it is particularly important to avoid a deterioration in cognitive performance;
      and, (iv) patients who failed to respond to previous treatment with sodium
      channel blocker agents as they may particularly benefit from the introduction of
      tiagabine, due to its GABAergic mechanism of action. Tiagabine can also be used
      successfully in other patients with refractory partial epilepsy. Tiagabine is not
      indicated for patients with generalized or unclassified epilepsies and for
      patients with severely impaired liver function.

PMID- 10962216
TI  - Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine.
AB  - OBJECTIVE: To evaluate plasma homocysteine (Hcy) concentrations in children
      receiving sodium valproate (VPA) and carbamazepine (CBZ), monotherapy, in
      comparison with healthy control subjects and to determine the possible
      relationship between Hcy levels and dosage and plasma concentrations of the
      antiepileptic drugs. METHODS: We measured levels of fasting and post-methionine
      Hcy, plasma pyridoxal 5'-phosphate (PLP, active vitamin B6), serum folate,
      erythrocyte folate and serum vitamin B12 in 60 epileptic patients (29 females, 31
      males), aged from 14.2 to 17.9 years, subdivided into two groups according to
      their therapy. Sixty-three healthy sex- and age-matched children served as
      controls. These measurements have been performed before the beginning of therapy
      and after 1 year of therapy with VPA or CBZ. RESULTS: Before the beginning of
      therapy, there were no significant differences in fasting and post-methionine
      Hcy, plasma PLP, serum folate, erythrocyte folate and serum vitamin B12 values
      between the control group and the two groups of epileptic children. After 1 year
      of therapy, patients treated with VPA and CBZ showed a significant increase of
      the plasma concentrations of Hcy when compared to baseline data and controls
      values. Moreover, was observed a significant decrease of serum folate and plasma
      PLP. On the contrary, serum vitamin B12 and erythrocyte folate levels remained in
      the normal range. CONCLUSIONS: Our study demonstrates that prolonged treatment
      with VPA and CBZ increases plasma concentrations of Hcy.

PMID- 10962217
TI  - Valproate metabolism during valproate-associated hepatotoxicity in a surviving
      adult patient.
AB  - The plasma profiles of valproate (VPA), its beta-oxidation metabolites E-2-en-VPA
      and 3-oxo-VPA and its terminal desaturation metabolite 4-en-VPA, have been
      measured in a patient receiving NaVPA 1000 mg twice per day from early in the
      course of serious hepatotoxicity and for 2 weeks after the drug was stopped.
      Concurrent profiles of liver, renal and haematological function parameters were
      available. Relative to concurrent plasma VPA concentrations, E-2-en-VPA
      concentrations were not different to those of the VPA-treated epileptic
      population at any stage of the illness, whereas 3-oxo-VPA concentrations relative
      to concurrent VPA concentrations were abnormally high early in the toxicity,
      abnormally low at its peak (3-5 days later), and comfortably within normal limits
      for the treated epileptic population late in the recovery phase (9-13 days from
      the onset). When measurable, plasma 4-en-VPA concentrations were not elevated.
      The elimination half-life of VPA during the recovery phase was 100 h, which is
      some 6-12 times greater than values reported for this parameter in normal
      patients. These data clearly define, in this patient, a link between
      idiosyncratic VPA-associated hepatotoxicity at its onset and peak and the later
      stages of VPA beta-oxidation. Whether the beta-oxidation abnormalities are
      causative or a consequence of an as yet undefined defect is unknown. In this
      patient, 4-en-VPA was unlikely to have been involved in the pathogenesis of the
      toxicity.

PMID- 10962218
TI  - Relationships between interleukins, neurotransmitters and psychopathology in drug
      free male schizophrenics.
AB  - It has been postulated that altered interleukin (IL) regulation may be involved
      in the pathogenesis of schizophrenia. We therefore investigated the relationships
      between interleukins, neurotransmitters, and psychopathology in schizophrenia. IL
      1beta, IL-2, IL-6, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5
      HIAA) were measured in the plasma of neuroleptic-free male schizophrenics in
      comparison to age-matched healthy male controls (n=25 each). The patients'
      psychopathology was assessed by the Scale for the Assessment of Positive and
      Negative Symptoms (SAPS, SANS). The above variables were measured during acute
      states of illness and after eight weeks of treatment with haloperidol. The plasma
      levels of IL-2 and HVA were significantly higher in patients compared to
      controls. In schizophrenic patients, there were significant correlations between
      IL-2 and HVA, IL-2 and SAPS, and HVA and SAPS during the acute state of illness.
      The level of IL-6 was significantly correlated to SANS and duration of illness.
      In schizophrenic patients, the plasma levels of IL-2 and HVA were significantly
      lowered after treatment with haloperidol. Changes in IL-2 and HVA significantly
      correlated to those in HVA and SAPS, respectively. These results strongly suggest
      that the cytokines may modulate dopaminergic metabolism and schizophrenic
      symptomatology in schizophrenia.

PMID- 10962219
TI  - Association study of a functional serotonin transporter gene polymorphism with
      schizophrenia, psychopathology and clozapine response.
AB  - Serotonin is implicated in the pathogenesis of schizophrenia. Following serotonin
      release, the serotonin transporter (5-HTT) is the major determinant of serotonin
      inactivation. The present study tested the hypothesis that a biallelic
      polymorphism in the 5' regulatory region of the 5-HTT gene (5-HTTLPR) confers
      susceptibility to schizophrenia, association with the clinical manifestations of
      schizophrenia or clozapine response. 90 treatment-resistant schizophrenic
      patients were assessed using the Brief Psychiatric Rating Scale before and after
      clozapine treatment. The results demonstrated that the 5-HTTLPR variants did not
      play a major role in the susceptibility, clinical manifestations or clozapine
      response in schizophrenia.

PMID- 10962220
TI  - Inverse correlation between hallucinations and serum prolactin in patients with
      non-affective psychoses.
AB  - Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free
      patients suffering from non-affective psychoses. A clear-cut negative correlation
      was found between the Comprehensive Psychiatric Rating Scale (CPRS) items
      assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation
      was observed between clinical measures (total CPRS score, schizophrenia subscale
      score or depression and anxiety subscale score) and serum PRL.

PMID- 10962221
TI  - Adjunctive imipramine for a broader group of post-psychotic depressions in
      schizophrenia.
AB  - As an expansion of work examining the usefulness of adjunctive imipramine added
      to fluphenazine decanoate and benztropine in the treatment of post-psychotic
      depression, a previously successful and informative protocol was extended to a
      larger and more heterogeneous cohort of clinic and day-treatment patients.
      Although the benefit of the adjunctive antidepressant strategy was still
      observable in the total sample, as calculated by the prospectively intended data
      analysis, the findings were weaker than those obtained for the initial cohort.
      Owing to the possibility that differences between the later and earlier cohorts
      might account for the muted nature of the benefit, a post-hoc analysis was
      undertaken. This revealed that the later cohort was sicker in general and more
      psychotic in particular. The later cohort was also treated with lower doses of
      neuroleptic medication while remaining out of hospital longer, consistent with
      more recent treatment trends. It was also possible that the later cohort was
      subtly selected for more refractoriness of depression, since treatment of post
      psychotic depression with adjunctive antidepressants had become more commonplace,
      and patients responding to this in general practice would not have gone on to be
      referred to the study. Thus a benefit from adjunctive antidepressant medication
      persists, but more remains to be learned about its character and likelihood in
      specific situations.

PMID- 10962223
TI  - EEG resonant responses in schizophrenia: a photic driving study with improved
      harmonic resolution.
AB  - Twenty seven drug-free schizophrenic patients and 25 normal controls were studied
      in an EEG photic driving paradigm with an improved harmonic resolution.
      Consistent with previous results, the present data show that schizophrenics have
      lower EEG responses to photic stimulation in alpha frequency. The differences
      between normal and schizophrenic subjects were distributed across major brain
      areas except centro-temporal regions. It also demonstrated that 1-Hz narrow
      pulsed stimulation was feasible in EEG photic driving studies. The enhanced
      harmonic resolution produced significantly more information in the frequency
      domain about EEG oscillatory responses to visual stimulus. Using this new
      technique, the authors showed for the first time that alpha photic driving was a
      well defined resonant system and that the group differences in harmonic responses
      were primarily confined in the high frequency portion of alpha band, suggesting a
      peak frequency shift of EEG resonance in schizophrenia.

PMID- 10962222
TI  - Delayed onset of late movement-related cortical potentials and abnormal response
      to lorazepam in catatonia.
AB  - Catatonia is a psychomotor syndrome with an inability to execute and terminate
      movements completely, leading consecutively to akinesia and posturing, which both
      respond almost immediately to benzodiazepines, i.e. gaba-potentiators like
      lorazepam. However, pathophysiological mechanisms of cortical motor and gaba
      ergic dysfunction remain unclear. We therefore investigated movement-related
      cortical potentials (MRPs) and movement kinematics during a motor task before and
      after lorazepam. Ten akinetic catatonic patients were compared with 10
      psychiatric (similar age, sex, medication, and underlying psychiatric disease but
      without catatonic syndrome) and 20 healthy controls. MRPs from frontal (F),
      central (C), and parietal (P) sites were recorded to obtain measures of early and
      late readiness potential and movement potential. Kinematic measures included
      parameters for amplitude of movements, peak velocity, average duration of
      movements, elevation angle, and angle velocity. The motor task consisted in self
      initiated extension of the right index finger. All catatonic and psychiatric
      control patients received intravenous lorazepam (1mg), whereas healthy controls
      were subjected to a placebo-controlled (10 received lorazepam, 10 received
      placebo) double-blind study design.Catatonics showed a significantly delayed
      onset of late readiness and movement potential in central electrodes (Cz, C3)
      compared with psychiatric and healthy controls. This delayed onset correlated
      significantly with catatonic motor symptoms and movement duration. Lorazepam led
      to significantly stronger delays in onset of late readiness potential in left
      fronto-parietal (F3, C3, P3) electrodes in catatonic patients than in psychiatric
      and healthy controls. It is concluded that delayed latencies in late MRP
      components in catatonic patients may reflect their inability to execute and
      terminate movements completely. Differential and stronger response to lorazepam
      in catatonia suggests dysfunction in inhibitory control of cortical motor
      function with increased gaba-ergic sensitivity.

PMID- 10962224
TI  - Asymmetrical olfactory acuity and neuroleptic treatment in schizophrenia.
AB  - Uni-rhinal olfactory acuity in schizophrenia was investigated in two experiments.
      The first assessed the presence of a predicted atypical asymmetry of nostril
      laterality and the second assessed the effect of antipsychotic treatment on the
      asymmetry. Although olfactory identification impairment has been well documented
      in schizophrenia, olfactory acuity has been neglected. This may be an oversight
      as cerebral structures of the mesial temporal lobe important to olfactory
      perception have often been implicated in the pathophysiology of schizophrenia and
      it is thus reasonable to postulate a primary impairment of olfactory acuity in
      schizophrenia. In addition, unmedicated patients with schizophrenia have
      exhibited asymmetrical laterality favouring the right over the left hemisphere in
      studies of visual, haptic, and auditory perception, and the few published
      prospective treatment studies have suggested a reversal of this asymmetry with
      first generation neuroleptic treatments. In experiment 1 a generalization of the
      perceptual asymmetry to olfactory acuity was examined by measurement of n-butanol
      olfactory thresholds with the Connecticut Chemosensory Perception Exam (CCPE) in
      an unmedicated sample of 17 patients with schizophrenia and 17 age, gender, and
      handedness matched normal controls. The patient sample showed an asymmetrical
      impairment of the left nostril that was not apparent in the normal control
      sample. In experiment 2, the CCPE was administered to a new sample of 10 patients
      with schizophrenia before and after neuroleptic treatment. The asymmetry observed
      in experiment 1 was replicated, and the relative advantage of the right nostril
      shifted to a relative advantage of the left nostril over the course of 8weeks of
      treatment. Results are discussed in relation to cerebral aspects of schizophrenia
      and potential implications to cognitive change from treatment.

PMID- 10962225
TI  - The hypothalamic-pituitary-thyroid axis in patients with schizophrenia.
AB  - Serum concentrations of thyroxine (T(4)), triiodothyronine (T(3)), reverse
      triiodothyronine (rT(3)) and thyrotropine (TSH) were measured in 31 acutely ill
      in-patients with schizophrenia before and after four weeks of treatment with the
      phenothiazine derivative perazine. The serum levels of all the above hormones
      were also determined in 19 schizophrenic patients in remission who were receiving
      no medication, 20 schizophrenic patients in remission taking neuroleptic drugs,
      and 24 patients with residual-type schizophrenia. The serum levels of T(4) of
      acutely ill schizophrenic patients were elevated, while those of T(3), rT(3) and
      TSH were normal. Their T(4) levels showed a positive correlation with the
      severity of illness and the degree of clinical response to neuroleptic treatment.
      There was a significant fall in serum concentrations of T(4) and rT(3) during
      four weeks of drug treatment and the decrease was significantly correlated to
      clinical response. No abnormalities in the serum concentrations of any of the
      hormones measured were found in schizophrenic patients in remission or in
      residual-type schizophrenia. In conclusion, our results indicate that the
      elevated serum levels of T(4) may be specific for acutely ill schizophrenic
      patients and that neuroleptic medication may affect thyroid hormone metabolism,
      this interaction being involved in the mechanism of action of these drugs.

PMID- 10962226
TI  - Immune-biochemical interactions in schizophrenia.

PMID- 10962227
TI  - Improvement of intestinal absorption of peptides: adsorption of B1-Phe
      monoglucosylated insulin to rat intestinal brush-border membrane vesicles.
AB  - In a previous study we glycosylated insulin to improve its intestinal absorption.
      When the glycosylated product, p-(succinylamido)-phenyl-alpha-D-glucopyranoside
      (SAPG)-substituted insulin (SAPG-INS), was administered intra-intestinally to
      rats, it showed a greater hypoglycemic effect than native bovine insulin. The
      enhanced hypoglycemic effect of SAPG-INS was considered to be due to an increase
      in membrane permeability as well as an increase in resistance to enzymatic
      degradation. In particular, membrane permeability may be related to an
      interaction with the Na(+)-dependent D-glucose transporter (SGLT-1) which is
      located in the brush-border membrane of epithelial cells. The insulin product
      used in the previous study, however, comprised a mixture of mono-, di- and tri
      SAPG-substituted insulin. In this study SAPG-INS with a defined substitution
      number and position was synthesized to examine the interaction between the
      transporter and glycosylated insulin in more detail. The new product was mono
      SAPG-substituted insulin substituted at the B1-phenylalanine position (B1-SAPG
      INS) and was selectively synthesized after protection of the A1-glycine and
      varepsilonB29-lysine amino acids. The hypoglycemic effect of B1-SAPG-INS in rats
      after an intravenous dose of 71 microg/kg was almost the same as that of native
      bovine insulin at a dose of 1 U/kg and B1-SAPG-INS retained about 60% of the
      immunoreactivity of native bovine insulin. The interaction of B1-SAPG-INS with
      the intestinal transporter was examined by a rapid filtration technique using
      (125)I-labeled B1-SAPG-INS and brush-border membrane vesicles (BBMVs) which were
      prepared from rat small intestine by the Mg-precipitation method. The amount of
      B1-SAPG-INS adsorbed or absorbed by BBMVs in the presence of an inward Na(+)
      gradient into BBMVs was greater than that of native bovine insulin. This
      adsorption/absorption was significantly inhibited by the presence of 1 mM
      phloridzin. A similar inhibition was observed when Na(+) was replaced with K(+)
      and when B1-SAPG-INS was incubated with BBMVs at 4 degrees C. From the effect of
      osmolarity on the extent of adsorption/absorption, it was considered that B1-SAPG
      INS was not taken up into the intravesicular space but adsorbed onto the external
      membrane surface of BBMVs. These findings suggested that B1-SAPG-INS was adsorbed
      specifically onto the transporter. The hypoglycemic effect of insulin was
      enhanced by glycosylation at the B1 position in in situ experiments using normal
      and diabetic rats. Consequently, it is suggested that B1-SAPG-INS was adsorbed
      specifically onto the glucose transporter of intestinal BBM. This specific
      adsorption may be involved in the mechanism of the enhanced hypoglycemic effect
      of B1-SAPG-INS both in normal and diabetic rats.

PMID- 10962228
TI  - Regional oral absorption, hepatic first-pass effect, and non-linear disposition
      of salmon calcitonin in beagle dogs.
AB  - The dose-dependent disposition, first pass hepatic elimination, and absorption
      pharmacokinetics (PK) of salmon calcitonin (sCT) were investigated in a canine
      Intestinal Vascular Access Port (IVAP) model. The PK of sCT were determined after
      intravenous (IV), subcutaneous (SC), portal venous (PV), and oral (PO)
      administration of sCT. Regional oral absorption of unformulated sCT was also
      evaluated by direct administration into the duodenum (ID), ileum (IL), and colon
      (IC) by means of surgically implanted, chronic catheters. Plasma samples were
      collected and analyzed by radioimmunoassay (RIA). Salmon calcitonin PK were
      evaluated using 2-compartmental and model independent methods. Intravenous sCT PK
      were non-linear over the dose range studied. High dose groups (100-1000 microg)
      demonstrated higher total plasma clearance (CL) and V(dss) than the low dose
      groups (1-25 microg). However, the MRT did not change for doses ranging from 10
      to 1000 microg. After SC administration, the absorption of sCT was rapid with
      bioavailability (BA) varying from 21.4 to 52.9%. However, the BA of sCT was low
      after ID, IL, and IC administration (0.039, 0.064, and 0.021%, respectively). The
      role of hepatic first-pass elimination was negligible. The results of these
      studies demonstrate that the elimination of sCT is rapid but does not occur in
      the liver. Enhanced sCT clearance at higher doses was indicated by increasing
      V(dss) values, and it is hypothesized that increased renal blood flow and/or
      saturated plasma protein binding may contribute to the non-linear behavior. The
      IVAP canine model was found to have utility for probing the absorption and
      disposition PK of sCT. The combination of high oral bioavailability variability
      and non-linear disposition of sCT may produce highly variable therapeutic
      effects. The practical impact of the non-linear disposition of sCT remains to be
      determined. Based on the current results it appears that the rate-limiting step
      to the successful oral administration of sCT is its delivery into the portal vein
      since hepatic metabolism was negligible.

PMID- 10962229
TI  - Enhancement of oral absorption of metronidazole suspension in humans.
AB  - The purpose of this study was to investigate oral absorption of two metronidazole
      suspension products, Flagyl((R)) and a test product. Twenty-four healthy
      volunteers participated in the study. The crossover study was done in a two
      phase, two-sequence manner with a 2-week washout period. Individual disposition
      kinetics were determined by non-compartmental analysis. AUC(0-infinity) and
      C(max) values were 1.26 and 1.86 times more in the case of test formulation. Mean
      plasma drug concentrations were analyzed to estimate the rate and extent of oral
      absorption. The optimized duodenal, jejunal1, jejunal2, illial1, ileal2, ilial3,
      ilial4, colonic permeability values (x10(-4)) for the test and Flagyl products
      were 3.96, 3.96, 3. 96, 0.68, 0.37, 0.01, 0.12, 0.38 and 2.34, 0, 0, 1.2, 1.1,
      0.9, 0.3, 0.04cm/s, respectively. The total fraction of oral dose absorbed for
      the test and Flagyl products were 95.5% and 65.6% respectively, consistent with
      the pharmacokinetic ratios. The test product exhibited significantly higher
      absorption rate and extent than Flagyl, but both show similar half-lives.
      Sensitivity analysis showed that drug absorption is sensitive to effective
      permeability but not sensitive to particle radius and small intestinal transit
      time. The two products were found bio-inequivalent which is suggested to be due
      to differences in formulation additives that decreased the effective permeability
      of Flagyl.

PMID- 10962230
TI  - Enhanced permeation of triamcinolone acetonide through the buccal mucosa.
AB  - To develop new formulations that have suitable bioadhesive force and provide
      sustained release in buccal area for an extended period of time, bioadhesive gels
      containing triamcinolone acetonide were prepared using two polymers, carbopol 934
      and poloxamer 407 which were selected for their bioadhesiveness and gelling
      property, respectively. The drug release profiles from the gels were studied as a
      function of drug concentration and temperature. Different enhancers such as bile
      salts, glycols and non-ionic surfactants were used for the enhancement of its
      permeation through buccal mucosa. Among the enhancers used, sodium deoxycholate
      showed the best enhancing effects.

PMID- 10962232
TI  - Radiolabelled biodegradable microspheres for lung imaging.
AB  - The effect on lung accumulation of modifying the surface compositions of (99m)Tc
      poly(lactide-co-glycolide) (PLGA) and (99m)Tc poly(ethylene glycol)-poly(lactide
      co-glycolide) (PEG-PLGA) microspheres with different surfactants was assessed
      after intravenous injection into rats. Microspheres were prepared with PLGA or
      PEG-PLGA by the emulsion solvent evaporation method using polyvinyl alcohol
      (PVA), polyethylene glycol (PEG), albumin (BSA) or poloxamer 188 as surfactant,
      in the external aqueous phase. Commercial human albumin microspheres
      (Sferotec((R)), HAM) were used as reference. According to the European
      Pharmacopeia, >80% of (99m)Tc-HAM in the size range 10-50 microm, must be
      accumulated in the lung 15 min after intravenous administration. By modifying the
      surfactant, the resulting lung accumulation was 99% for (99m)Tc-HAM, and more
      than 50% for PLGA microspheres prepared with poloxamer 188 (1 and 4%), reaching
      67% with 8% Poloxamer 188 and around 30-39% for PLGA and PEG-PLGA microspheres
      prepared with the other surfactants. PLGA microspheres made with 8% poloxamer 188
      gave good quality lung images under a gamma camera for the first few minutes,
      subsequently liver radioactivity masked lung images.

PMID- 10962231
TI  - Use of floating alginate gel beads for stomach-specific drug delivery.
AB  - Two types of alginate gel beads capable of floating in the gastric cavity were
      prepared. The first, alginate gel bead containing vegetable oil (ALGO), is a
      hydrogel bead and its buoyancy is attributable to vegetable oil held in the
      alginate gel matrix. The model drug, metronidazole (MZ), contained in ALGO was
      released gradually into artificial gastric juice, the release rate being
      inversely related to the percentage of oil. The second, alginate gel bead
      containing chitosan (ALCS), is a dried gel bead with dispersed chitosan in the
      matrix. The drug-release profile was not affected by the kind of chitosan
      contained in ALCS. When ALCS containing MZ was administered orally to guinea
      pigs, it floated on the gastric juice and released the drug into the stomach.
      Furthermore, the concentration of MZ at the gastric mucosa after administration
      of ALCS was higher than that in the solution, though the MZ serum concentration
      was the same regardless of which type of gel was administered. These release
      properties of alginate gels are applicable not only for sustained release of
      drugs but also for targeting the gastric mucosa.

PMID- 10962233
TI  - Considerations in the use of hydroxypropyl-beta-cyclodextrin in the formulation
      of aqueous ophthalmic solutions of hydrocortisone.
AB  - The in vivo ocular bioavailability of hydrocortisone (HC) in the NZW rabbit was
      determined following topical administration of solutions containing HC (1%) with
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) alone, or containing the
      mucoadhesive, viscosity enhancing polymers sodium hyaluronate (0.2 and 0.5% w/v)
      or Carbopol 934P (0.1% w/v). A 1% HC suspension was used as control. Formulation
      of HC as a solution with HP-beta-CD in the absence of polymer increased the
      bioavailability of HC in the aqueous humour by approximately 55% and cornea by
      75% when compared to suspension. Inclusion of either polymer did not result in
      any further increase in ocular bioavailability over that noted for the polymer
      free solution. The in vitro corneal permeability of HC was also evaluated. A
      linear relationship (r(2)=0.999) was noted between corneal permeability and the
      concentration of free (uncomplexed) HC in solution. Permeability was greatest
      when formulated either as a suspension, or as an HP-beta-CD solution in which the
      concentration of free (uncomplexed) HC is equivalent to that of a saturated
      solution. Thus, when using cyclodextrins in the reformulation of ophthalmic
      suspensions as solutions, consideration must be given to the concentration of
      cyclodextrin used and to the benefits of including viscosity enhancing polymers.

PMID- 10962234
TI  - Effect of skin pretreatment with fatty acids on percutaneous absorption and skin
      retention of piroxicam after its topical application.
AB  - The enhancing effect of several fatty acids from different subclasses: saturated
      (lauric acid), mono-unsaturated (oleic acid) and poly-unsaturated (linoleic and
      linolenic acids) in the percutaneous absorption of piroxicam was investigated.
      These fatty acids were applied on the skin membrane in three different ways:
      included in the vehicle, as a pretreatment or both. An increase in piroxicam flux
      value was found for lauric and oleic acids in the following order: skin
      pretreatment with 5% fatty acids followed by application of gels containing 5%
      fatty acids>skin pretreatment with 5% fatty acids followed application of control
      gel>gel containing 5% fatty acids without skin pretreatment. For linoleic and
      linolenic acids, the piroxicam flux in the two pretreatment experiments was
      almost the same, although higher than when fatty acids were included in the
      formulation. Skin pretreatment with 5% linolenic acid in propylene glycol
      followed by application of control gel or a gel containing 5% linolenic acid,
      showed the highest enhancing capacity. After skin pretreatment with fatty acids,
      the lag time values decreased nearly three times compared to those obtained when
      the same fatty acids were included in the formulation. The amount of piroxicam
      retained in the skin after pretreatment with fatty acids was found to be very
      similar for all fatty acids and 3-fold higher than in the experiments without
      skin pretreatment.

PMID- 10962235
TI  - A poly(ortho ester) designed for combined ocular delivery of dexamethasone sodium
      phosphate and 5-fluorouracil: subconjunctival tolerance and in vitro release.
AB  - A viscous hydrophobic poly(ortho ester) (POE) has been developed as a
      biocompatible, biodegradable sustained release system for selected cases of
      glaucoma filtering surgery. Dexamethasone and 5-fluorouracil (5-FU) are
      frequently administered together post-operatively, for their anti-fibroblastic
      and anti-inflammatory properties, respectively. A combined sustained release of
      both drugs could be advantageously used. Drug release kinetics were studied using
      specially designed thermostated cells. Subconjunctival tolerance was evaluated on
      New Zealand albino rabbits by clinical evaluation. Due to its basicity, the
      addition of dexamethasone sodium phosphate (DEX-P) stabilized the polymer and
      prolonged 5-FU in vitro release from 2 to 4 days. Both therapeutic agents were
      released concomitantly, according to a linear profile. The presence of 5-FU only
      slightly affected the overall subconjunctival tolerance of POE in rabbits,
      whereas the addition of DEX-P markedly improved POE tolerance by reducing the
      hyperemia of the conjunctiva to a minimal grade.

PMID- 10962236
TI  - Controlled release of drugs from injectable in situ formed biodegradable PLGA
      microspheres: effect of various formulation variables.
AB  - A novel in situ method for the preparation of injectable biodegradable
      poly(lactide-co-glycolide) (PLGA) microspheres for the controlled delivery of
      drugs is described here. A stable dispersion of PLGA microglobules
      ('premicrospheres' or 'embryonic microspheres') in a vehicle mixture on
      injection, comes in contact with water from aqueous buffer or physiological
      fluid, thereby hardening the microglobules into solid matrix type microparticles
      entrapping the drug (in situ formed microspheres). The drug is then released from
      these microspheres in a controlled fashion. The effect of the following
      formulation variables on the characteristics of the novel drug delivery system
      (NDDS) was investigated: (i) the concentrations of polyethylene glycol 400 (PEG
      400), the encapsulated drug, and the hydrophilic excipient (mannitol); and (ii)
      the types of encapsulated drug (micromolecules and macromolecules such as
      protein) and vehicles (replacing triacetin and Miglyol 812 by triethyl citrate
      and soybean oil respectively). Also, the effect of formulation, process, and
      storage (15 days/4 degrees C) conditions on the physical stability of the
      encapsulated protein was evaluated. The in vitro drug release was enhanced with
      decrease in the PEG 400 concentration and increase in the drug and mannitol
      concentration. The drug release was retarded with increase in the molecular
      weight of the encapsulated drug. Substitution of triacetin by triethyl citrate
      and miglyol 812 by soybean oil resulted in variation in the release of the drug
      from the in situ formed microspheres. A preliminary investigation of the physical
      stability of the myoglobin revealed that the alpha-helical structure was
      unaffected by the formulation, process, and the storage conditions.

PMID- 10962237
TI  - Polymer and microsphere blending to alter the release of a peptide from PLGA
      microspheres.
AB  - The objective of this study was to evaluate the effect of polymer and microsphere
      blending in achieving both a sufficient initial release and a desired continuous
      release of a peptide from poly(D, L-lactide-co-glycolide) microspheres.
      Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a
      solvent-extraction/evaporation process and were characterized for their drug
      load, bulk density, size distribution, surface area, surface morphology, in vitro
      drug release, and in vivo efficacy. Combining PLGA polymers that varied in their
      molecular weights in various ratios yielded microspheres with varied drug release
      profiles commensurate with the hydration tendencies of the polymers. Increasing
      the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa
      increased the initial drug release. A similar microsphere formulation prepared
      instead with blending microspheres from individual polymers showed a similar
      increase. In an animal model, microspheres obtained from polymer or microsphere
      blends attained a faster onset of testosterone suppression as compared to
      microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3
      kDa, alone. These studies illustrated the feasibility of blending polymers or
      microspheres of varied characteristics in achieving modified drug release. In
      particular the increased initial release of the peptide could help avoid the
      therapeutic lag phase usually observed with microencapsulated macromolecules.

PMID- 10962238
TI  - In-line moisture measurement during granulation with a four-wavelength near
      infrared sensor: an evaluation of particle size and binder effects.
AB  - Factors affecting in-line near infrared (NIR) moisture measurement with a four
      wavelength sensor were evaluated (choice of binder used in granulation liquid and
      the increase in particle size). An entire NIR spectrum is not necessary for the
      measurement of water, and often the use of only a few NIR wavelengths around the
      water band enables reliable and high-speed detection of moisture. Glass ballotini
      and microcrystalline cellulose (MCC) were used as model test materials. The
      binders studied were poly[1-(2-oxo-1-pyrrolidinyl)ethylene] (PVP) and gelatin.
      Full off-line NIR spectra of test materials at different levels of binder
      solutions were measured. The major spectral features for both the binders were
      bands around 1700 nm (first overtones CH related stretches) and 2200 nm
      (combination bands). Gelatin also had an NH band around 1500 nm (first overtones
      of NH stretches) and combination bands at about 2050 nm. Particle size effects
      were observed as an increase in spectra baseline. All these factors should be
      considered when choosing NIR wavelengths used for detection of water with a fixed
      wavelength set-up. A robust calibration model enables the development of in
      process control of wet granulation processes.

PMID- 10962239
TI  - Influence of relative humidity on the mechanical and drug release properties of
      theophylline pellets coated with an acrylic polymer containing methylparaben as a
      non-traditional plasticizer.
AB  - The purpose of this study was to investigate the influence of relative humidity
      (RH) on the mechanical and dissolution properties of theophylline pellets coated
      with Eudragit((R)) RS 30 D/RL 30 D containing methylparaben (MP) as a non
      traditional plasticizer. The coated beads were stored at 23 degrees C and at
      different relative humidities (0, 29, 51, 75 and 84% RH). The effect of storage
      conditions on the rate of drug release from coated beads was determined in pH 7.4
      phosphate buffer solution. The mechanical properties, including tensile strength
      and Young's modulus, of individual beads were determined by a diametral
      compression method with a Chatillon((R)) tension/compression apparatus. The
      morphology of the intact and fractured beads was investigated using scanning
      electron microscopy (SEM). The moisture content of the polymeric films was
      determined using a Karl Fischer coulometric moisture analyzer. The results from
      the mechanical studies demonstrated that an increase in the relative humidity
      resulted in a decrease in the tensile strength and Young's modulus of the coated
      beads. SEM photographs showed that coated beads stored at 0% RH exhibited brittle
      fracture failure. The coated beads stored at 84% RH showed ductile behavior,
      which was attributed to the hydroplasticization effect on the acrylic polymer due
      to the uptake of moisture. The moisture content in the films was also shown to
      influence the rate of drug release from Eudragit((R)) RS 30 D/RL 30 D coated
      beads containing MP as the plasticizer. The change in release profiles could be
      minimized when the relative humidity was reduced to zero. The dissolution rate of
      theophylline from the coated beads decreased when stored at high relative
      humidities. This trend was reversed when the coated beads that were stored at 84%
      RH for 5 weeks, were then equilibrated at 0% RH.

PMID- 10962240
TI  - Development of disintegrating multiple-unit tablets on a high-speed rotary tablet
      press.
AB  - Enteric coated bisacodyl pellets were compressed into divisible disintegrating
      tablets on a high speed rotary tablet press and investigated for pellet damages.
      The degree of pellet damages was examined via the bisacodyl dissolution during
      the acid treatment of' the drug release test for enteric coated articles
      according to USP 23. The damages depended on the type of filler-binder used and
      settings of the tablet press. Avicel PH 101 proved to be the most suitable filler
      binder, effecting homogeneous distribution of the pellets within the tablets, as
      could be shown by image analysis of coloured pellets. The speed of the tablet
      press had noo influence on the pellet damages using Avicel PH 101 as a filler
      binder, however, tablets containing 70% (w/w) of coated pellets did not fulfil
      the requirements of USP 23, despite optimum elasticity and coating thickness of a
      new Eudragit FS 30 D coating. Reducing the proportion of pellets to 60% per
      tablet, less than 10% of bisacodyl were released within 2 h during acid treatment
      thus fulfilling the requirements of the USP 23.

PMID- 10962241
TI  - Three-dimensional modeling to determine properties of tableting materials on
      rotary machines using a rotary tableting machine simulator.
AB  - A new three-dimensional modeling technique of tableting data has been used for
      data measured with a rotary tableting machine simulator. The use of the tableting
      machine simulator is helpful in this case because a scale up or a change of
      equipment is easily possible. The model substances used were hydroxypropyl
      methylcellulose (HPMC 15.000), microcrystalline cellulose (Avicel PH 101),
      dicalcium phosphate dihydrate (Emcompress) and theophylline monohydrate, four
      very differently deforming substances. Tablets were produced by simulating a
      Manesty Betapress with 100 rev./min. The materials were tableted to five graded
      maximum relative densities (rho(rel, max)) of 0.75, 0.80, 0.85, 0.90 and 0.95. A
      twisted plane was fitted to the measured data and three parameters: d, the time
      plasticity: e, the pressure plasticity and omega, the elastic decompression,
      resulted for each material at the given rho(rel, max) according to the three
      dimensional tableting technique. The results show different parameter-plots for
      the tableting materials, allowing to differentiate between the tableting
      characteristics of various substances. Three-dimensional modeling of data from
      rotary machines is shown to be a valuable tool not only for material
      characterization on eccentric machines but on rotary tableting machines as well.

PMID- 10962242
TI  - Biopharmaceutical characterization of oral theophylline and aminophylline
      tablets. Quantitative correlation between dissolution and bioavailability
      studies.
AB  - Considering the narrow therapeutic index of theophylline and the low range
      between the safe and toxic serum concentrations of this drug, the study of its
      pharmacokinetic properties is necessary. However, considering the time consuming
      and expensive in vivo tests, quantitative correlation between in vivo
      bioavailability and in vitro dissolution tests can be used routinely in quality
      control tests of these drug products to predict the in vivo pharmacokinetic
      parameters. For this reason healthy human volunteers were used for in vivo
      studies and serum samples were analyzed by a fluorescence polarization
      immunoassay analysis (FPIA) method. The results showed that an open one
      compartmental model could best describe the pharmacokinetic properties of orally
      administered theophylline and aminophylline tablets. Linear regression analysis
      by least-square method showed a good correlation between some in vivo and in
      vitro parameters obtained from dissolution studies by rotating basket and paddle
      methods. D(30)% (percentage of drug dissolved in vitro after 30 min) and F(0.5)%
      (drug absorbed in vivo after half an hour calculated by Wagner-Nelson equation)
      showed best correlation (r=0. 99036). C(max) (maximum serum concentration) of
      this drug also correlates well with t(25%) (time required to dissolve 25% of the
      drug). The calculated correlation coefficients could best predict the actual
      values of some pharmacokinetic parameters; AUC(0-->infinity), AUC(0-->1), F(0.5)%
      and C(max).

PMID- 10962243
TI  - Interactions between hydroxypropylcelluloses and vapour/liquid water.
AB  - Understanding of the uptake of water vapour or liquid water by cellulose-based
      polymers is important because of the influence of these processes on many of the
      biologically or technologically relevant properties of these polymers. In this
      work we studied these processes in the cases of twelve hydroxypropylcelluloses
      with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively),
      characterization of which showed significant differences in structural and
      physical parameters (substitution pattern, crystallinity, particle size, specific
      surface area, and intraparticular porosity). Water vapour sorption-desorption
      isotherms determined to characterize the uptake of water vapour were fitted well
      by the Young-Nelson model, the optimized parameters of which indicated that at
      all relative humidities the capacity to bind water vapour as a surface monolayer
      is greater for HPCs than L-HPCs, but the capacity to absorb water vapour
      internally is greater for L-HPCs than HPCs. Guggenheim-Anderson-deBoer (GAB)
      models fitted the sorption-desorption isotherms less well. Differential scanning
      calorimetry (DSC) experiments showed all sorbed water vapour to be held as non
      freezing water. Isoperibol microcalorimetry experiments carried out to
      investigate interactions with liquid water showed enthalpies of
      hydration/dissolution of between -62.86 and -71.35 J g(-1) for L-HPCs and between
      -82.95 and -99.80 J g(-1) for HPCs, and DSC showed average numbers of non
      freezing water molecules per polymer repeat unit of 2.65-4.19 for L-HPCs and
      18.10-22.42 for HPCs. DSC characterization of the kinetics of the water uptake by
      10 mg compacts obtained by direct compression of hydroxypropylcelluloses showed
      faster uptake by L-HPC compacts than by HPC compacts, among which there were
      significant differences in capacity for diffusive uptake. The explanations of the
      above differences in terms of the different substituent contents, particle sizes
      and porosities of the HPCs is supported by multiple linear regression analyses.

PMID- 10962244
TI  - Mercury porosimetry of microcrystalline cellulose tablets: effect of scanning
      speed and moisture.
AB  - The effect of pretreatment and scanning speed of mercury porosimetry on the
      porosity result of microcrystalline cellulose tablets was studied. The porosity
      parameters followed were total pore volume, mean and median pore size, and volume
      pore size distribution. Scanning speed did not affect the total pore volume of
      tablets compressed from microcrystalline cellulose. With increasing speed, the
      smallest pores of powder tablets were not properly determined, which increased
      the mean pore size. The median pore size of tablets compressed from powder and
      granules decreased and the maximum at the pore size range 500-1000 nm changed
      towards smaller pores with increasing scanning speed. Scanning speed appears to
      affect in different ways the samples with different physical structures. In
      tablet samples, scanning speed affects the volume of the pores at the whole pore
      size range determined. Thus, it is important to use about the same, reasonably
      low scanning speed in the measurements when comparing the samples. Swelling of
      microcrystalline cellulose in tablet samples is observed by mercury porosimetry
      measurement; a change in the pore structure is detected after storage at 88%
      relative humidity as increased total pore volumes and median pore sizes. Due to
      swelling, the maximum at the pore size range 500-2000 nm changed towards larger
      pores with increasing moisture. Swelling is observed similarly in tablets
      manufactured from powder and granules. When storing in humid conditions, water
      fills the smallest pores of microcrystalline cellulose powder tablets, hinders
      the intrusion of mercury and, thus, the mean pore size increases. Contrary to
      this, the volume of the smallest pores of granule tablets compressed with the
      highest compression pressure increased with increasing moisture. Careful
      pretreatment before the measurements is important.

PMID- 10962246
TI  - Central 5-HT(1A) receptors: regional distribution and functional characteristics.
AB  - Among the multiple receptors for serotonin identified to date, the 5
      hydroxytryptamine (5-HT)(1A) type is among the best known because selective
      ligands have been available for more than 15 years. Radioactive derivatives
      allowed the demonstration of the presence of 5-HT(1A) binding sites mainly in the
      limbic areas and the raphe nuclei in the brain, where they correspond to
      postsynaptic receptors and "presynaptic" autoreceptors, respectively. This review
      article summarizes key data on the molecular, pharmacological, and differential
      functional properties of pre- versus postsynaptic 5-HT(1A) receptors.

PMID- 10962247
TI  - Psychopharmacology of 5-HT(1A) receptors.
AB  - Serotonin(1A) (5-HT(1A)) receptors are located on both 5-HT cell bodies where
      they act as inhibitory autoreceptors and at postsynaptic sites where they mediate
      the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT(1A)
      receptors in humans can be measured using the technique of pharmacological
      challenge. For example, acute administration of a selective 5-HT(1A) receptor
      agonist, such as ipsapirone, decreases body temperature and increases plasma
      cortisol through activation of pre- and postsynaptic 5-HT(1A) receptors,
      respectively. Use of this technique has demonstrated that unmedicated patients
      with major depression have decreased sensitivity of both pre- and postsynaptic 5
      HT(1A) receptors. Treatment with selective serotonin reuptake inhibitors further
      down-regulates 5-HT(1A) receptor activity. Due to the hypotheses linking
      decreased sensitivity of 5-HT(1A) autoreceptors with the onset of antidepressant
      activity, there is current interest in the therapeutic efficacy of combined
      treatment with selective serotonin reuptake inhibitors and 5-HT(1A) receptor
      antagonists.

PMID- 10962248
TI  - A retrospect on the discovery of WAY-100635 and the prospect for improved 5
      HT(1A) receptor PET radioligands.
AB  - Abstract. An outline is given of the developments that led to the identification
      of [O-methyl-(11)C]WAY-100635 (4) as the first useful PET ligand for imaging
      serotonin(1A) (5-HT(1A)) receptors in the living human brain. Recent attempts to
      develop 5-HT(1A) receptor radioligands superior to 4 are reviewed, and [carbonyl
      (11)C]WAY-100635 (6) has been shown to be the best currently available
      radioligand for human studies. Of other (11)C-radiolabelled compounds, [O-methyl
      (11)C](R,S)-CPC-222 (9), DWAY (8), and [(11)C]NAD-299 (14) all demonstrate
      specific binding to 5-HT(1A) receptors in animals and warrant further expedited
      studies in humans. The trans-fluorocyclohexane, 12, and fluorobenzene, [(18)F]p
      MPPF 13, are highlighted as examples of promising (18)F-labelled ligands.

PMID- 10962249
TI  - Radioligands for the study of brain 5-HT(1A) receptors in vivo--development of
      some new analogues of way.
AB  - [Carbonyl-(11)C]WAY-100635 (WAY) has proved to be a very useful radioligand for
      the imaging of brain 5-HT(1A) receptors in human brain in vivo with positron
      emission tomography (PET). WAY is now being applied widely for clinical research
      and drug development. However, WAY is rapidly cleared from plasma and is also
      rapidly metabolised. A comparable radioligand, with a higher and more sustained
      delivery to brain, is desirable since these properties might lead to better
      biomathematical modelling of acquired PET data. There are also needs for other
      types of 5-HT(1A) receptor radioligands, for example, ligands sensitive to
      elevated serotonin levels, ligands labelled with longer-lived fluorine-18 for
      distribution to "satellite" PET centres, and ligands labelled with iodine-123 for
      single photon emission computerised tomography (SPECT) imaging. Here we describe
      our progress toward these aims through the exploration of WAY analogues,
      including the development of [carbonyl-(11)C]desmethyl-WAY (DWAY) as a promising,
      more brain-penetrant radioligand for PET imaging of human 5-HT(1A) receptors, and
      (pyridinyl-6-halo)-analogues as promising leads for the development of
      radiohalogenated ligands.

PMID- 10962250
TI  - Fluoro analogs of WAY-100635 with varying pharmacokinetics properties.
AB  - Radiolabeled derivatives of WAY-100635 have been shown to be important for
      imaging in vivo because of their antagonist properties and their specificity for
      the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor. Our goal is to prepare a series
      of radiofluorinated derivatives of WAY-100635 that, in the rat, range in
      pharmacokinetic properties from nearly irreversible to reversible in their
      behavior. It appears that derivatives containing a cyclohexanecarboxylic acid
      (e.g., FCWAY) with its high affinity and high target to nontarget contrast, has
      properties suited to measure receptor concentration. Derivatives based on
      phenylcarboxamide (e.g., FBWAY and MeFBAWAY) have properties more suited to the
      measurement of changes in endogenous serotonin. The compound containing the
      pyrimidine moiety in place of the pyridine moeity in FBWAY (FBWAY 1,3N) appears
      to have intermediate properties.

PMID- 10962251
TI  - Imaging the 5-HT(1A) receptors with PET: WAY-100635 and analogues.
AB  - This paper summarizes our work on WAY-100635 and analogues, labeled either with
      carbon-11 or fluorine-18, as potential radioligands for the 5
      hydroxytryptamine(1A) (5-HT(1A)) neuroreceptors. Other facets of our work
      include: (1) human studies with [O-methyl-(11)C]WAY-100634, the major radioactive
      metabolite of [O-methyl-(11)C]WAY-100635, and with [(11)C]CPC 222; (2) use of a
      human liver metabolism model to screen in vitro potential metabolic problems in
      humans; (3) modification of the "dry method" to prepare [carbonyl-(11)C]WAY
      100635; and (4) validation studies in humans with [carbonyl-(11)C]WAY-100635.

PMID- 10962252
TI  - [(18)F]p-MPPF: aA radiolabeled antagonist for the study of 5-HT(1A) receptors
      with PET.
AB  - This paper summarizes the present status of the researches conducted with
      [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]
      piperazine known as [(18)F]p-MPPF, a new 5-HT(1A) antagonist for the study of the
      serotonergic neurotransmission with positron emission tomography (PET). This
      includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with
      autoradiography and PET, human data with PET, toxicity, and metabolism.

PMID- 10962253
TI  - Quantitative imaging of 5-HT(1A) receptor binding in healthy volunteers with
      [(18)f]p-MPPF.
AB  - Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p
      [(18)F]fluorobenzamido+ ++] ethylpiperazine ([(18)F]p-MPPF) can be used for 5
      hydroxytryptamine(1A) (5-HT(1A)) receptor imaging. The aim of this study was to
      develop a method for the quantitative imaging of 5-HT(1A) receptors in healthy
      volunteers with [(18)F]p-MPPF. After injection of [(18)F]p-MPPF radioactivity was
      rapidly taken up in the brain, with the highest accumulation in the medial
      temporal cortex. Low levels of radioactivity were found in cerebellum and basal
      ganglia. Plasma clearance and metabolism of [(18)F]p-MPPF resulted in only about
      1% of the radioactivity in plasma as parent radioligand after 10 min. Using a
      linear graphical method (Logan-Patlak), binding potentials were calculated in
      several brain areas. A good correlation (r = 0.95) was found between the obtained
      binding potentials and literature values for 5-HT(1A) receptor densities. A good
      correlation (r = 0.96) was also found between the body weight-corrected
      region/cerebellum ratios and the respective binding potentials. Moreover, a
      blocking experiment with pindolol (n = 3) showed a decrease of 40% in the
      region/cerebellum ratios of the target areas. Compared to those of [carbonyl
      (11)C]WAY-100635, the binding potentials were four to six times lower, indicating
      that [(18)F]p-MPPF has a lower in vivo affinity for 5-HT(1A) receptors. In
      conclusion, [(18)F]p-MPPF can be used for the quantitative analysis of 5-HT(1A)
      receptor distribution in human brain.

PMID- 10962254
TI  - Quantitative analysis of [carbonyl-(11)C]WAY-100635 PET studies.
AB  - [carbonyl-(11)C]WAY-100635 ?[(11)C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1
      yl)ethyl)-N-(2- pyridy l)cyclohexanecarboxamide? is a positron-emission
      tomography (PET) radioligand for in vivo imaging of the 5-hydroxytryptamine(1A)
      (5-HT(1A)) receptor. This paper assesses and summarises various different
      modeling strategies for the quantitative analysis of the radioligand. The models
      considered are based on a compartmental description of the ligands behaviour and
      include both plasma input analyses, requiring the additional monitoring of blood
      activity, and a reference tissue approach, which relies solely on the tomographic
      tissue data. Parameter estimates of specific binding are presented for a set of
      test-retest data, obtained from six normal volunteers who were scanned on two
      separate occasions, allowing for an assessment of normal binding values and their
      reproducibility.

PMID- 10962255
TI  - Quantification of [Carbonyl-(11)C]WAY-100635 binding: considerations on the
      cerebellum.
AB  - The specific binding of [carbonyl-(11)C]WAY-100635 to 5-hydroxytryptamine(1A)
      receptors was quantitated using different kinetic models. Ten healthy subjects
      were studied using a GE Advance PET scanner. We suggest that tissue heterogeneity
      explains part of the nonspecific binding seen in cerebellum, which leads to an
      underestimation of binding potential with reference tissue methods. The nonlinear
      three-compartmental model with metabolite-corrected plasma input provides
      accurate estimates of receptor binding because of the favorable kinetics of
      tracer in the brain and circulation.

PMID- 10962256
TI  - Derivation of [(11)C]WAY-100635 binding parameters with reference tissue models:
      effect of violations of model assumptions.
AB  - In several positron-emission tomography studies of human subjects, analyses of
      data from the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor radioligand, [(11)C]WAY
      100635 ?[carbonyl-(11)C]N-(2-(4-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N -(2 
      pyridyl)cyclohexanecarboxamide? have shown a discrepancy between the outcome
      measure k(3)/k(4) (binding potential normalized to cerebellum) as estimated by
      the simplified reference region method and results obtained by conventional
      kinetic modeling with an arterial input function. The reference region method has
      yielded results that are lower than the conventional approach, with the relative
      underestimation appearing to be an increasing function of k(3)/k(4). We performed
      simulations on idealized data to identify the source of the discrepancy. Both the
      simplified reference tissue model (SRTM) and the original full reference tissue
      model (FRTM) were tested to determine (a) if the error in estimated k(3)/k(4) is
      dependent on the blood flow in the region of interest relative to the blood flow
      in the region of reference (R(1)) and on the receptor density in the region of
      interest (true k(3)/k(4)), and (b) which violation of the reference model
      assumptions were responsible for this effect. FRTM returned parameter estimates
      that were independent and accurate if the reference region was constructed
      precisely as a one-tissue compartment model. SRTM overestimated k(3)/k(4) when
      the reference region was constructed as a one-tissue compartment model and
      underestimated k(3)/k(4) when the reference region was constructed as a two
      tissue compartment model (which is the case for [(11)C]WAY-100635). In both
      cases, the magnitude of the error in k(3)/k(4) returned by SRTM was dependent on
      true R(1) and true k(3)/k(4). In conclusion, the SRTM is associated with a bias
      in the derivation of k(3)/k(4) that is not a simple scaling factor. This
      magnitude of these errors should be carefully evaluated for each new radioligand.

PMID- 10962257
TI  - PET evaluation of [(18)F]FCWAY, an analog of the 5-HT(1A) receptor antagonist,
      WAY-100635.
AB  - We synthesized [(18)F]FCWAY, an analog of [carbonyl-(11)C]WAY-100635 ?[(11)C]N-(2
      (1-(4-(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(pyridi
      nyl))cyclohexanecarboxamide?, by replacing the cyclohexanecarbonyl group acid
      with a trans-4-fluorocyclohexanecarbonyl group (FC). Control and preblocking
      studies were performed in anesthetized monkeys. Plasma radioactive metabolite
      analysis showed the presence of [(18)F]FC and [(18)F]fluoride. Tissue time
      radioactivity curves were corrected for metabolite contamination based on
      separate positron-emission tomography studies of these two labeled metabolites.
      Analysis using a two-tissue compartment model gave distribution volume (V)
      estimates (mL/mL) ranging from 33 in frontal cortex to 4 in cerebellum.
      Preblocking data showed uniform V of 2-3 mL/mL. These studies demonstrate that
      [(18)F]FCWAY has very similar kinetic characteristics to [(11)C]WAY-100635.

PMID- 10962259
TI  - Drug action at the 5-HT(1A) receptor in vivo: autoreceptor and postsynaptic
      receptor occupancy examined with PET and [carbonyl-(11)C]WAY-100635.
AB  - Serotonin(1A) (5-HT(1A)) receptors have been implicated in the pathophysiology
      and treatment of anxiety and depression and are a target for novel drug
      development. In this qualitative study, positron emission tomography (PET) and
      [carbonyl-(11)C]WAY-100635 were used to assess 5-HT(1A) autoreceptor and
      postsynaptic receptor occupancy in man in vivo by five different compounds with
      nanomolar affinity for this site. Occupancy by pindolol, penbutolol, buspirone,
      EMD 68843, and S 15535 was compared to test-retest data from 10 healthy
      volunteers. All drugs, apart from buspirone, displayed occupancy at the 5-HT(1A)
      receptor site. Pindolol demonstrated a preferential occupancy at the autoreceptor
      compared to the postsynaptic receptor over a plasma range of about 10-20 ng/mL.
      Differential occupancy may be an important component of novel drug action. The
      level of autoreceptor or postsynaptic occupancy needed to achieve significant
      physiological effects is not known, although it is of note that none of the drugs
      in this study achieved occupancies beyond 60%. Overall this study demonstrates
      the utility of PET in aiding novel drug development.

PMID- 10962258
TI  - Serotonin type-1A receptor imaging in depression.
AB  - Regional 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential (BP) of
      depressed subjects with primary, recurrent, familial mood disorders was compared
      to that of healthy controls by using positron emission tomography and [carbonyl
      (11)C]WAY-100635 ?[(11)C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-
      pyridy l)cyclohexanecarboxamide?. The mean 5-HT(1A) receptor BP was reduced 42%
      in the midbrain raphe and 25-33% in limbic and neocortical areas in the
      mesiotemporal, occipital, and parietal cortex. The magnitude of these
      abnormalities was most prominent in bipolar depressives and unipolar depressives
      who had bipolar relatives. These abnormal reductions in 5-HT(1A) receptor BP are
      consistent with in vivo evidence that 5-HT(1A) receptor sensitivity is reduced in
      major depressive disorder and postmortem data showing a widespread deficit of 5
      HT(1A) receptor expression in primary mood disorders.

PMID- 10962260
TI  - Use of PET and the radioligand [carbonyl-(11)C]WAY-100635 in psychotropic drug
      development.
AB  - Positron-emission tomography (PET) provides potential in neuropsychiatric drug
      development by expanding knowledge of drug action in the living human brain and
      reducing time consumption and costs. The 5-hydroxytryptamine(1A) (5-HT(1A))
      receptor is of central interest as a target for the treatment of anxiety,
      depression, and schizophrenia. Research on the clinical significance of the 5
      HT(1A) receptor now benefits from the highly selective radioligand [carbonyl
      (11)C]WAY-100635 (WAY) for quantitative determination of 5-HT(1A) receptors in
      the primate and human brain in vivo using PET. In this paper, three studies are
      reviewed to demonstrate the suitability of WAY as radioligand for quantification
      of central 5-HT(1A) receptors in brain and as an applicable tool for drug
      development. In the first study a monkey model was used to characterize WAY
      binding. It was confirmed that the reference ligand 8-OH-DPAT and psychoactive
      drugs such as buspirone and pindolol occupies 5-HT(1A) receptors in the primate
      brain. Pindolol is an beta-adrenoreceptor antagonist with a high affinity to 5
      HT(1A) receptors. This drug has been suggested in combination with selective
      serotonin reuptake inhibitors for the treatment of depression and was given to
      healthy males in the second study. Pindolol induced a marked inhibition of
      central 5-HT(1A) receptors as calculated by the ratio-analysis method and
      simplified reference tissue model, 2 h after administration of 10 mg as a single
      oral dose. This observation suggests that pindolol may have a role for the
      suggested potentiation of selective serotonin reuptake inhibitor treatment of
      depression. The third study was on robalzotan (NAD-299), a recently developed 5
      HT(1A) receptor antagonist and putative drug with implications for the treatment
      of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100
      microg/kg IV occupied 5-HT(1A) receptors in a dose-dependent and saturable manner
      with a maximal calculated occupancy of 70-80%. The relationship between
      robalzotan plasma concentration and 5-HT(1A) receptor occupancy could be
      described by a hyperbolic function that was used to guide the selection of
      appropriate doses in man. In a subsequent PET study of robalzotan binding to 5
      HT(1A) receptors in the living human brain, similar results have been replicated
      recently. These studies reviewed here illustrate and corroborate that
      quantitative neuroimaging of receptor binding has potential for the evaluation
      and dose finding of new central nervous system drugs.

PMID- 10962261
TI  - Positron emission tomography study of pindolol occupancy of 5-HT(1A) receptors in
      humans: preliminary analyses.
AB  - Preclinical studies in rodents suggest that augmentation of serotonin reuptake
      inhibitors (SSRIs) therapy by the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor
      agent pindolol might reduce the delay between initiation of treatment and
      antidepressant response. This hypothesis is based on the ability of pindolol to
      potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an
      effect achieved by blockade of the 5-HT(1A) autoreceptors in the dorsal raphe
      nuclei (DRN). However, placebo-controlled clinical studies of pindolol
      augmentation of antidepressant therapy have reported inconsistent results. Here,
      we evaluated the occupancy of 5-HT(1A) receptors following treatment with
      controlled release pindolol in nine healthy volunteers with positron-emission
      tomography (PET). Each subject was studied four times: at baseline (scan 1),
      following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak
      level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and
      following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol
      occupancy of 5-HT(1A) receptors was evaluated in the DRN and cortical regions as
      the decrease in binding potential (BP) of the radiolabelled selective 5-HT(1A)
      antagonist [carbonyl-(11)C]WAY-100635 or [carbonyl-(11)C] N-(2-(4-(2
      methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cyclohexa necarboxamide
      abbreviated as [(11)C]WAY-100635. Pindolol dose-dependently decreased [(11)C]WAY
      100635 BP. Combining all the regions, occupancy was 20 +/- 8% at scan 2, 14 +/-
      8% at scan 3, and 44 +/- 8% at scan 4. The results of this study suggest that at
      doses used in clinical studies of augmentation of the SSRI effect by pindolol
      (2.5 mg t.i.d.), the occupancy of 5-HT(1A) receptors is moderate and highly
      variable between subjects. This factor might explain the variable results
      obtained in clinical studies. On the other hand, at each dose tested, pindolol
      occupancy of 5-HT(1A) receptors was higher in the DRN compared to cortical
      regions, demonstrating a significant in vivo selectivity for DRN 5-HT(1A)
      autoreceptors relative to cortico-limbic postsynaptic receptors. This selectivity
      is necessary for the potentiation of 5-HT transmission, and this finding
      represents an important proof of concept in the development of 5-HT(1A) agents
      for this application. Early evaluation of new drugs with PET imaging will enable
      rapid screening of compounds based on DRN selectivity and more appropriate
      determination of doses for clinical trials.

PMID- 10962263
TI  - Heart donor management and expansion of current donor selection criteria

PMID- 10962262
TI  - Cardiovascular and peripheral rehabilitation

PMID- 10962264
TI  - The case against outpatient parenteral inotropic therapy for advanced heart
      failure

PMID- 10962265
TI  - Mitral valve repair in cardiomyopathy

PMID- 10962266
TI  - Determination of candidacy for mechanical circulatory support: importance of
      clinical indices

PMID- 10962268
TI  - Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy:
      tissue parasitism and endogenous IFN-gamma as important determinants of chemokine
      mRNA expression during infection with Trypanosoma cruzi.
AB  - We investigated the kinetics of parasite replication, leukocyte migration, and
      cytokine/chemokine mRNA expression in the heart tissue from animals infected with
      the Colombiana strain of Trypanosoma cruzi. Cardiac tissue parasitism was
      noticeable at 15 days, peaked around 30 days and was dramatically reduced at 120
      days postinfection (p.i.). Kinetic studies showed that the inflammatory
      infiltrate was dominated by the presence of alphabetaT CD3(+ )CD4(+ )CD8(-),
      alphabetaT CD3(+ )CD4(-)CD8(+ )lymphocytes and macrophages. The mRNA expression
      of the monokines IL-1beta and IL-12(p40) was elevated at 15 days p.i. and
      controlled at later time points. In contrast, TNF-alpha mRNA was expressed
      throughout the infection. Interestingly, we found that at 15 and 30 days p.i.
      cytokine expression was dominated by the presence of IFN-gamma mRNA, whereas at
      60 days or later time points the balance of type 1 and type 2 cytokines was
      switched in favor of IL-4 and IL-10 mRNAs. The chemokine mRNAs encoding JE, MIP
      1alpha, MIP-1beta, KC, and MIP-2 were all mainly expressed at 15 and/or 30 days
      p.i. and diminished thereafter. In contrast, the expression of RANTES, MIG and IP
      10 mRNAs was augmented at 15 days p.i. and persisted at high levels up to 120
      days p.i. Taken together, our results indicate that regulation of IFN-gamma and
      chemokine expression, associated with decreased tissue parasitism, may be largely
      responsible for the control of inflammation and immunopathology observed in the
      cardiac tissue of animals infected with T. cruzi.

PMID- 10962269
TI  - Signal transduction in the protozoan host Hartmannella vermiformis upon
      attachment to Legionella pneumophila.
AB  - Intracellular replication of the Legionnaires' disease bacterium, Legionella
      pneumophila, within protozoa plays a major role in bacterial ecology and
      pathogenesis. Invasion of the protozoan host Hartmannella vermiformis by L.
      pneumophila is mediated by attachment to the Gal/GalNAc lectin receptor, which is
      similar to the beta(2) integrin transmembrane receptors of mammalian cells.
      Bacterial invasion is associated with induction of a protein tyrosine phosphatase
      (PTPase) activity in H. vermiformis that results in tyrosine dephosphorylation of
      the lectin receptor and several cytoskeletal proteins. In this report, we show
      that entry of L. pneumophila into H. vermiformis is not required to induce
      tyrosine dephosphorylation of one of the cytoskeletal proteins, paxillin.
      Tyrosine dephosphorylation of paxillin is mediated at the level of bacterial
      attachment to the lectin receptor, and is blocked by inhibiting bacterial
      attachment to the lectin receptor. Attachment of L. pneumophila to the lectin
      receptor is not mediated by the type IV pilus, which is one of the bacterial
      ligands involved in attachment to protozoa. Interestingly, the lectin receptor in
      resting H. vermiformis is associated with several phosphorylated proteins that
      are dissociated upon bacterial attachment and invasion. We show that the L.
      pneumophila-induced PTPase activity in H. vermiformis and the associated tyrosine
      dephosphorylation of host proteins can be mimicked by the cytoskeletal disrupting
      agent, cytochalasin D. Taken together, our data indicate that attachment of L.
      pneumophila to the lectin receptor of H. vermiformis induces a PTPase activity,
      tyrosine dephosphorylation of the lectin and cytoskeletal proteins, dissociation
      of the lectin from its associated phosphorylated proteins, and most probably
      disassembly of the cytoskeleton. This novel L. pneumophila-protozoa interaction
      may be a bacterial strategy to invade protozoa and to be trafficked into a
      replicative 'niche', or to block differentiation of the protozoan host into a
      cyst in which L. pneumophila cannot replicate.

PMID- 10962270
TI  - Adherence and intracellular parasitism of Paracoccidioides brasiliensis in Vero
      cells.
AB  - Paracoccidioides brasiliensis is a dimorphic fungus known to produce invasive
      systemic disease in humans. The 43-kDa glycoprotein of P. brasiliensis is the
      major diagnostic antigen of paracoccidioidomycosis and may act as a virulence
      factor, since it is a receptor for laminin.Very little is known about early
      interactions between this fungus and the host cells, so we developed in vitro a
      model system employing cultured mammalian cells (Vero cells), in order to
      investigate the factors and virulence mechanisms of P.brasiliensis related to the
      adhesion and invasion process. We found that there is a permanent interaction
      after 30 min of contact between the fungus and the cells. The yeasts multiply in
      the cells for between 5 and 24 h. Different strains of P. brasiliensis were
      compared, and strain 18 (high virulence) was the most strongly adherent, followed
      by strain 113 (virulent), 265 (considered of low virulence) and 113M (mutant
      obtained by ultraviolet radiation, deficient in gp43). P. brasiliensis adhered to
      the epithelial cells by a narrow tube, while depressions were noticed in the cell
      surface, suggesting an active cavitation process. An inhibition assay was
      performed and it was verified that anti-gp43 serum and a pool of sera from
      individuals with paracoccidioidomycosis were able to inhibit the adhesion of P.
      brasiliensis to the Vero cells. Glycoprotein 43 (gp43) antiserum abolished 85% of
      the binding activity of P. brasiliensis. This fungus can also invade the Vero
      cells, and intraepithelial parasitism could be an escape mechanism in
      paracoccidioidomycosis.

PMID- 10962271
TI  - Intranasal, rectal and intraperitoneal immunization with protoxin Cry1Ac from
      Bacillus thuringiensis induces compartmentalized serum, intestinal, vaginal and
      pulmonary immune responses in Balb/c mice.
AB  - Recently we discovered that the Cry1Ac protoxin of Bacillus thuringiensis
      administered to Balb/c mice intraperitoneally (i.p.) or intragastrically is a
      systemic and intestinal immunogen as potent as cholera toxin. To further
      characterize the mucosal immunogenicity of Cry1Ac we additionally tried the
      intranasal (i.n.) and rectal routes and used enzyme-linked immunoassays to
      determine anti-Cry1Ac antibody responses in the serum as well as in vaginal and
      tracheobronchial washes and in the fluids of the large and the small intestine.
      Immunization by the i.p., i.n. and rectal routes induced IgM, IgG and IgA
      antibodies in all the mucosal surfaces analyzed, but the magnitude and
      predominant isotype of each response depended on the route used and the mucosal
      site analyzed. These data extend our findings on the striking mucosal
      immunogencity of Cry1Ac and provide additional evidence on the
      compartmentalization of the mucosal immune system.

PMID- 10962272
TI  - Host life history responses to parasitism.
AB  - Parasites and their infections can adversely effect a host's growth, reproduction
      and survival. These effects are often not immediate, but increase with time since
      infection. A general prediction from evolutionary biology is that hosts suffering
      from this type of infection should preferentially allocate resources towards
      reproduction, even if this is at the expense of their growth and survival. This
      review illustrates this argument with several empirical studies showing hosts
      behaving in this manner. These studies indicate that one way for hosts to reduce
      the costs of parasitism is by altering their life history traits to bring forward
      their schedule of reproduction.

PMID- 10962273
TI  - The oral cavity as a reservoir of bacterial pathogens for focal infections.
AB  - Dental procedures, but more importantly, oral infections and poor oral health can
      provoke the introduction of oral microorganisms into the bloodstream or the
      lymphatic system. The subsequent attachment and multiplication of these bacteria
      on tissues or organs can lead to focal oral infections. Pathogenic agents may
      also remain at their primary oral site but the toxins liberated can reach an
      organ or tissue via the bloodstream and cause metastatic injury. Finally,
      metastatic inflammation may result from an immunological injury caused by oral
      bacteria or their soluble products that enter the bloodstream and react with
      circulating specific antibodies to form macromolecular complexes.

PMID- 10962274
TI  - Mechanisms of bacterial resistance and response to bile.
AB  - Enteric bacteria are resistant to the bactericidal effects of intestinal bile,
      but these resistance mechanisms are not completely understood. It is becoming
      increasingly apparent that enteric bacteria have evolved to utilize bile as a
      signal for the temporal production of virulence factors and other adaptive
      mechanisms. A greater understanding of the resistance and response of bacteria to
      bile may assist the development of novel therapeutic, prevention, and diagnostic
      strategies to treat enteric and extraintestinal infections.

PMID- 10962275
TI  - The wild hidden face of Lyme borreliosis in Europe.
AB  - Lyme borreliosis is a zoonosis affecting humans in the Northern hemisphere. The
      pathogen, Borrelia burgdorferi sensu lato (sl), persists in endemic areas through
      a maintenance cycle involving ticks and wild animals. The description of
      different genospecies associated with Lyme borreliosis in Europe has generated
      the question concerning the maintenance of these pathogens in nature: how do
      closely related bacterial species like B. burgdorferi sl circulate between one
      main tick species, Ixodes ricinus, and several vertebrate host species? Recent
      studies have provided evidence that specific associations exist in some areas
      between Borrelia species and vertebrate hosts. The present paper based on this
      recent knowledge discusses various aspects of the ecology of the disease in
      Western Europe, in particular the maintenance and dispersal of the pathogens, and
      brings up some interesting questions.

PMID- 10962276
TI  - Molecular mechanisms of invasion by cancer cells, leukocytes and microorganisms.
AB  - Invasion is a phenotype common to cancer cells, leukocytes, parasites, bacteria
      and viruses, involving cell-cell adhesion, cell-matrix adhesion, proteolysis and
      motility. These activities are regulated by the cross talk between invaders and
      host. We discuss the invasion-related molecular interactions of E-cadherin,
      integrins, matrix metalloproteinases and the chemokine receptor RANTES.

PMID- 10962277
TI  - The role of the interleukin-1/Toll-like receptor superfamily in inflammation and
      host defence.
AB  - The IL-1 receptor/Toll-like receptor superfamily comprises a diverse family of
      cell surface receptors defined by a characteristic conserved sequence in their
      cytosolic regions, termed the Toll/IL-1 receptor domain, which function in
      inflammation and host defence against microbial pathogens. Members include
      receptors for the proinflammatory cytokines IL-1 and IL-18 and Toll-like
      receptors 2 and 4, which are involved in host responses to Gram-positive and Gram
      negative bacteria, respectively. Signalling pathways activated by these receptors
      are conserved and the superfamily represents a pan-genomic system involved in the
      host response to infection and injury.

PMID- 10962278
TI  - Plasmodium falciparumin the squirrel monkey (Saimiri sciureus): infection of non
      splenectomised animals as a model for exploring clinical manifestations of
      malaria.
AB  - Plasmodium falciparum infection in humans leads to a variety of symptoms ranging
      from an influenza-like syndrome to life-threatening complications. Animal models
      are useful tools for the detailed analysis of the interaction between both
      parasite and host factors leading to these various clinical manifestations. In
      this review, examining the different clinical, parasitological and haematological
      parameters associated with P. falciparum infection in spleen-intact monkeys, we
      propose this model as a good alternative for exploring some aspects of the host
      parasite relationship in malaria.

PMID- 10962279
TI  - Mycoplasma fermentans interaction with monocytes/macrophages: molecular basis.
AB  - Mycoplasmas are the smallest free-living self-replicating bacteria - having
      diameters of 200 to 800 nm - widely distributed in animals and plants. Mycoplasma
      fermentans is a human pathogen suspected to be involved in the progression of
      autoimmune diseases. Although pathogenesis mechanisms of M. fermentans are
      currently poorly understood, the role of these microorganisms as immunomodulatory
      agents is well established. In the present paper, we will review and discuss
      recent breakthroughs in the field.

PMID- 10962280
TI  - Pathogenicity of Erysipelothrix rhusiopathiae: virulence factors and protective
      immunity.
AB  - Erysipelothrix rhusiopathiae is the causative agent of erysipelas in animals and
      erysipeloid in humans. In the absence of specific antibodies, the organism evades
      phagocytosis by phagocytic cells, but even if phagocytized, it is able to
      replicate intracellulary in these cells. In this review, recent advances in our
      understanding of the pathogenicity of E. rhusiopathiae and its protective
      immunity are described.

PMID- 10962281
TI  - Why do we lack an effective vaccine against herpes simplex virus infections?
AB  - This review discusses the possible causes for the lack of an effective antiherpes
      vaccine. Future prospects of vaccines based on the current knowledge of immune
      responses to herpes viruses are discussed. It is argued that vaccines capable of
      expanding CD8 T-cell memory responses should be the focus of future anti-herpes
      simplex virus research.

PMID- 10962282
TI  - 'Infectious web'.
AB  - Infections by Helicobacter pylori are responsible for duodenal and gastric ulcers
      and are a significant risk factor for the development of gastric adenocarcinoma.
      H. pylori was discovered in 1983, but many institutes in Canada, Europe, and the
      United States are already involved in programs to understand and treat the
      infections, as reflected by the growing number of internet sites devoted to this
      bacterium. Most AIDS patients and about 20% of children with acute lymphoblastic
      leukemia develop Pneumocystis carinii pneumoniae. Information on clinical
      symptoms and treatment, as well as the P. carinii genome sequencing project, are
      described at several web sites. Students and researchers wishing to understand
      the correlation between telomere length and AIDS may turn to web sites of the
      University of Colorado and Washington University School of Medicine for the
      latest on telomeres and telomerase, and their function in aging and cancer.

PMID- 10962285
TI  - Characteristics of the cholesterol efflux induced by novel seminal phospholipid
      binding proteins.
AB  - Our recent results indicated that the major proteins of bovine seminal plasma
      (collectively called BSP proteins) stimulate cholesterol efflux from fibroblasts
      and that this process shows many differences compared to the efflux induced by
      apolipoprotein A-I (apoA-I)-containing lipoproteins. The present study was
      undertaken to investigate the BSP-mediated efflux mechanism. Compared to the slow
      and constant rate of cholesterol efflux induced by apoA-I-containing
      lipoproteins, the BSP proteins stimulated a rapid efflux that gradually reached a
      plateau. The addition of purified BSP proteins after the establishment of the
      plateau resulted in a further cholesterol efflux indicating that cellular
      cholesterol was still available for efflux. Incubation of unlabeled fibroblast
      culture with the spent medium containing BSP-generated lipid ([(3)H]cholesterol)
      particles obtained after the establishment of the plateau did not result in any
      cholesterol influx. Therefore, the plateau did not correspond to an equilibrium
      of the radiolabel between the medium and the cells but rather to a saturation of
      the efflux particles with cholesterol. Numerous studies have indicated that the
      cholesterol efflux induced by apoA-I-containing lipoproteins involves cell
      surface receptor, caveolae and intracellular cholesterol mobilization. Therefore,
      we investigated these characteristics for the BSP-mediated cholesterol efflux.
      Binding of BSP proteins to cells (evaluated by immunoblotting) reached saturation
      rapidly and remained constant thereafter. However, after several washings the
      cell-bound BSP proteins were unable to promote significant cholesterol efflux.
      Both results indicate no correlation of cholesterol efflux with cell binding.
      Moreover, in comparison to apoA-I-mediated cholesterol efflux, BSP-mediated
      efflux was not abolished at temperatures below 22 degrees C indicating that the
      BSP-induced cholesterol efflux does not involve intracellular cholesterol
      mobilization. High-density lipoprotein- and apoA-I-mediated cholesterol efflux
      was inhibited by preincubating fibroblasts with progesterone, whereas the
      cholesterol efflux by BSP proteins was not, indicating that cell-surface caveolae
      do not participate in BSP-mediated cholesterol efflux. Our results indicate that
      the mechanism of cholesterol efflux by BSP proteins is unidirectional and is
      strikingly different from that mediated by apoA-I-containing lipoproteins.

PMID- 10962286
TI  - Role of phosphatidic acid phosphatase 2a in uptake of extracellular lipid
      phosphate mediators.
AB  - Phosphatidic acid (PA) phosphatase 2a (PAP2a) is an integral membrane
      glycoprotein that hydrolyzes a number of structurally related lipid phosphate
      substrates when presented in mixed phospholipid and detergent micelles. The
      physiological substrate specificity and functions of this enzyme are unclear.
      Using reconstitution studies we demonstrate that PAP2a hydrolyses both PA and
      LysoPA substrates in a lipid bilayer. To investigate the activity of PAP2a
      against cellular substrates we generated HEK293 cell variants stably
      overexpressing the enzyme. Although one of these lines exhibited a 27-fold
      increase in PAP2 activity measured in vitro, levels of PA were not significantly
      reduced in comparison with control cells. Cell surface labeling and activity
      measurements demonstrate that a portion of the enzyme was localized to the cell
      surface. Pagano and Longmuir (J. Biol. Chem. 260 (1985) 1909) described the rapid
      uptake of PA by cultured cells, but the mechanisms and proteins involved were not
      identified. We found that overexpression of PAP2a was accompanied by a 2.1-fold
      increase in uptake of a fluorescent PA analog but that uptake of other
      phospholipids and diacylglycerols was unaltered. The increase in lipid uptake was
      completely dependent on PAP activity and unaffected by endocytosis inhibitors.
      Our results indicate that PAP2a is a cell surface enzyme that plays an active
      role in the hydrolysis and uptake of lipids from the extracellular space.

PMID- 10962288
TI  - Oxidation of unsaturated phospholipids in membrane bilayer mixtures is
      accompanied by membrane fluidity changes.
AB  - Steady-state and time-resolved fluorescence spectroscopy has been used to obtain
      information on oxidation processes and associated dynamical and structural
      changes in model membrane bilayers made from single unilamellar vesicles (SUV's)
      of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) mixed with increasing amounts
      of 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (SAPC). The highly
      unsaturated arachidonoyl chain containing four double bonds is prone to
      oxidation. Lipid oxidation was initiated chemically by a proper oxidant and could
      be followed on line via the fluorescence changes of an incorporated fluorescent
      lipophilic fatty acid: 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a
      diaza-s-indacene-3-undecanoic acid (BP-C11). The oxidation rate increases with an
      increasing amount of SAPC. Size measurements of different SUV's incorporated with
      a trace amount of a phosphatidylcholine analogue of BP-C11 using fluorescence
      correlation spectroscopy have demonstrated that an increase of lipid unsaturation
      results in smaller sized SUV's and therefore to a larger curvature of the outer
      bilayer leaflet. This suggests that the lipid-lipid spacing has increased and
      that the unsaturated fatty acyl chains are better accessible for the oxidant.
      Oxidation results in some characteristic physical changes in membrane dynamics
      and structure, as indicated by the use of specific fluorescence probes.
      Fluorescence measurements of both dipyrenyl- and diphenylhexatriene-labelled PC
      introduced in non-oxidised and oxidised DOPC-SAPC membranes clearly show that the
      microfluidity (local fluidity at the very site of the probes) significantly
      decreases when the oxidised SAPC content increases in the lipid mixture. A
      similar effect is observed from the lateral diffusion experiments using
      monopyrenyl PC in the same membrane systems: the lateral diffusion is distinctly
      slower in oxidised membranes.

PMID- 10962290
TI  - Mechanism of the phospholipid transfer protein-mediated transfer of phospholipids
      from model lipid vesicles to high density lipoproteins.
AB  - To study the effects of the phospholipid transfer protein (PLTP) on the
      thermodynamic parameters governing the transfer of phospholipids (PL) from single
      bilayer vesicles (SBV) to high density lipoprotein (HDL), we performed transfer
      measurements at various temperatures between 4 and 65 degrees C, using a
      pyrenylphosphatidylcholine (Pyr-PC) as probe. The proportion of excimer (E) to
      monomer (M) fluorescence of a pyrenyl moiety constitutes a direct measure of its
      local concentration. The transfers of Pyr-PC were monitored by following the
      decrease of E/M. The data were used to calculate the rate constants K(+1) for the
      transfer from SBV to HDL and to generate the corresponding Arrhenius plots. The
      equilibrium constants, K(eq), for the same reactions were also determined and
      used to generate Van't Hoff plots. From these data, we calculated the
      thermodynamic parameters for both the whole transfer reaction and the transition
      state. Both K(+1) and K(eq) values clearly varied with temperature. PLTP induced
      very similar decreases in the free energy for the whole reaction (DeltaG) and in
      that for the transition state (DeltaG(#)). At 37 degrees C, the decreases were of
      0.37 and 0.29 kcal/mol, respectively. We studied the thermal denaturation of PLTP
      between 37 and 65 degrees C, and the effects of denatured PLTP samples on the PL
      transfer reaction were then determined. In all cases, the changes of DeltaG
      remained comparable to those of DeltaG(#). Thus the essential action of PLTP is
      to facilitate the first step of the reaction, which can be considered as the
      desorption of PL molecules from the surface of donor particles.

PMID- 10962291
TI  - Increased cyclooxygenase-2 and 5-lipoxygenase activating protein expression in
      peritoneal macrophages during ovalbumin immunization of mice and cytosolic
      phospholipase A(2) activation after antigen challenge.
AB  - The present study investigates phenotypic and functional differentiation of
      peritoneal macrophages during ovalbumin-induced subcutaneous immunization of
      mice. For the first time we show that, in mouse peritoneal macrophages, ovalbumin
      immunization induces an increase in cyclooxygenase-2 (COX-2) and 5-lipoxygenase
      activating protein (FLAP) expression whereas it inhibits cytosolic phospholipase
      A(2) (cPLA2) expression. The study of arachidonic acid (AA) metabolism in
      peritoneal macrophages from control (cPM) and ovalbumin-immunized (iPM) mice
      shows that the reduced cPLA2 expression is correlated to a reduced basal AA
      metabolism, but is not a limiting factor for the opsonized zymosan-, PMA-, or
      A23187-triggered AA metabolism. We also show that in vitro ovalbumin challenge
      induces, only in iPM, cPLA2 activation through phosphorylation of serine
      residues, via a mechanism involving MAP kinases, and through increased
      intracellular calcium concentrations, leading to eicosanoid production. In
      parallel, we report that, in peritoneal macrophages, ovalbumin immunization
      induces the expression of CD23, the low affinity receptor for IgEs known for its
      involvement in allergic diseases. Thus, the modified expression of the enzymes
      involved in AA metabolism and the difference of response of cPM and iPM toward
      the antigen are important elements to understand the underlying mechanisms of
      ovalbumin-induced allergic responses.

PMID- 10962293
TI  - Artificial urethral sphincter for incontinence.

PMID- 10962294
TI  - Argument for sling surgery to replace bladder suspension for stress urinary
      incontinence.

PMID- 10962295
TI  - Microdialysis assessment of shock wave lithotripsy-induced renal injury.
AB  - OBJECTIVES: Shock wave lithotripsy (SWL) is the primary treatment modality for
      managing the majority of symptomatic renal calculi. However, the fundamental
      mechanisms for stone fragmentation and the resultant morphologic changes that
      occur are not fully understood. Furthermore, a thorough understanding of the
      complex biologic pathways involved in SWL-induced renal injury does not exist at
      present. To elucidate the biologic processes involved in tissue injury after SWL,
      an animal model was designed to mimic the pathogenesis of high-energy SWL in
      humans. METHODS: Juvenile female swine were anesthetized, and a midline
      laparotomy incision was performed to expose the right kidney. Using an introducer
      apparatus, a microdialysis probe was placed into the renal parenchyma of the
      right kidney lower pole and a tunnel was generated to exit the distal ends of the
      inlet and outlet tubing outside the body. After a 72-hour postoperative recovery
      period, SWL was performed to the lower pole renal region of the kidney, as a
      microdialysis pump continuously infused dialysate through the inlet tubing.
      Microdialysis fluids were collected during SWL, and lipid peroxidation, as
      measured by conjugated diene concentrations, was monitored. RESULTS: All
      microdialysis probes remained patent for a total of 2000 shock waves. A
      significant elevation in conjugated diene levels was observed in the SWL versus
      untreated kidneys after 1000 shock waves were administered (P <0.02).
      CONCLUSIONS: This animal model is unique in that it represents the first system
      for the real-time collection of renal interstitial fluids during SWL. Analysis of
      this fluid may provide insight into the physiologic mechanisms responsible for
      shock wave-induced renal injury.

PMID- 10962297
TI  - Favorable long-term outcome in adult genitourinary low-grade sarcoma.
AB  - OBJECTIVES: To report our experience treating sarcomas in 20 consecutive
      patients. METHODS: Pretreatment and follow-up data were obtained from 20 adult
      patients consecutively treated between 1992 and 1998 for primary or locally
      recurrent genitourinary sarcoma. RESULTS: Eight patients (40%) were classified as
      having high-grade and 12 (60%) low-grade disease. Except for 3 patients, the
      primary treatment was surgery alone. The median follow-up was 52 months. The
      actuarial disease-specific 5-year survival rate was 84% in all patients and was
      100% for patients with Memorial Sloan Kettering Cancer Center (MSKCC) Stages 1-2
      and 54% in MSKCC Stages 3-4. The disease-specific survival was significantly
      better in low-grade tumors (log-rank test, P = 0.0063) and inguinal-scrotal
      tumors (P = 0.019), tumors 5 cm or less (P = 0.039), and MSKCC Stages 1-2 tumors
      (P = 0.0035). CONCLUSIONS: The results of this study with a high proportion of
      low-grade, low-stage, and inguinal-scrotal sarcomas demonstrate the favorable
      prognosis of these subgroups.

PMID- 10962296
TI  - Association between a positive flow cytometry crossmatch and the development of
      chronic rejection in primary renal transplantation.
AB  - OBJECTIVES: With the current repertoire of immunosuppressants available, the
      results of organ transplantation are now very good in the short term. However,
      many grafts continue to be lost in the long term because of chronic rejection.
      This study examined the effect of kidney transplantation against a positive flow
      cytometry crossmatch (FCXM) on the subsequent development of chronic rejection
      and graft failure. METHODS: We examined 187 primary renal transplantations
      performed at our institution between 1993 and 1996. All of these patients had a
      negative cytotoxicity crossmatch. All had a pretransplant FCXM, and patients were
      divided according to the results of the FCXM into three categories: FCXM
      negative, FCXM class I positive, and FCXM class II positive. RESULTS: We found
      that a positive FCXM at the time of transplantation was strongly associated with
      the ultimate development of chronic rejection. In FCXM-negative individuals,
      16.9% developed chronic rejection compared with 80% of those with an HLA class I
      (T and B-cell) reaction and 40.9% of those with a class II (B-cell-only) reaction
      (P <0.001). The 3-year graft survival rate was 93% for FCXM-negative patients
      compared with 86% for FCXM class II positive and 80% for FCXM class I positive
      patients (P = 0.001). CONCLUSIONS: A strong association between a positive FCXM
      and subsequent development of chronic rejection was identified. This finding
      raises the possibility that more aggressive treatment of patients with a positive
      FCXM might ultimately result in a lower incidence of chronic rejection and
      improve overall graft survival.

PMID- 10962298
TI  - Stone recurrence after endopyelotomy.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether repair of the
      ureteropelvic junction (UPJ) obstruction reduces the incidence of stones in stone
      forming patients with concurrent UPJ obstruction. METHODS: We performed a
      retrospective study evaluating 90 patients with UPJ obstruction who underwent
      endopyelotomy and simultaneous stone extraction (group A) and 80 patients without
      UPJ obstruction who underwent only stone extraction (group B). Group A consisted
      of 52 men and 38 women with an average age of 54.4 years (range 15 to 82), and
      group B of 46 men and 34 women with an average age of 53.5 years (range 8 to 94).
      Metabolic evaluation was available in 47 patients of group A and 42 patients of
      group B. RESULTS: We achieved a stone-free state in all patients of both groups.
      Stone recurrence was observed in 7 patients (8%) in group A and in 32 patients
      (40%) in group B. Nine of 47 patients (19%) in group A showed metabolic
      abnormalities. In group B we found 30 of 42 patients (71.4%) with metabolic
      abnormalities. CONCLUSIONS: Our results suggest that correction of the anatomic
      obstruction facilitates the drainage of the previously entrapped urine, and thus
      decreases the incidence of recurrent urinary stone formation.

PMID- 10962299
TI  - Contemporary management of renal cell carcinoma with coexistent renal artery
      disease: update of the Cleveland Clinic experience.
AB  - OBJECTIVES: To treat concurrent renal cell carcinoma (RCC) and renal artery
      disease (RAD), which pose an unusual and challenging management dilemma. METHODS:
      Before June 1998, 48 patients presented with localized RCC and RAD affecting all
      the functioning renal parenchyma. These patients were grouped into four distinct
      categories: group 1, a solitary kidney with RCC and RAD (n = 8); group 2,
      bilateral RCC and coexistent RAD (n = 9); group 3, unilateral RCC and
      contralateral RAD (n = 15); and group 4, unilateral RCC and bilateral RAD (n =
      16). The most common cause of RAD was atherosclerosis (n = 40), followed by
      medial fibroplasia (n = 5), renal artery aneurysm (n = 2), and arteriovenous
      malformation (n = 1). RESULTS: All patients underwent complete surgical excision
      of RCC. A nephron-sparing operation was performed preferentially (44 patients),
      and bilateral renal cancer operations were staged. Eleven patients underwent
      surgical renal vascular reconstruction in conjunction with either partial (n = 9)
      or radical (n = 2) nephrectomy. In 2 patients, renal revascularization was
      accomplished by percutaneous transluminal angioplasty before tumor excision. No
      perioperative deaths occurred. Postoperatively, preservation of renal function
      was achieved in 47 patients; 1 patient required chronic dialysis. The overall and
      cancer-specific 5-year patient survival rates in this series were 66% and 90%,
      respectively. At a mean follow-up of 58 months, 28 patients were alive with no
      evidence of malignancy. Six patients died of metastatic RCC, and 14 died of
      unrelated causes with no evidence of malignancy. CONCLUSIONS: Nephron-sparing
      surgery combined with selective renal arterial reconstruction can yield
      gratifying results in this complex patient population.

PMID- 10962300
TI  - Nephron-sparing surgery of renal cell carcinoma with a normal opposite kidney:
      long-term outcome in 180 patients.
AB  - OBJECTIVES: To investigate the long-term outcome of an organ-saving approach for
      renal cell carcinoma (RCC) with a normal opposite kidney (elective indication).
      METHODS: Since 1979, 180 patients have undergone nephron-sparing surgery at our
      institution for RCC in the presence of a normal contralateral kidney. The mean
      age was 56 years (range 23 to 83), and the mean follow-up was 4.7 years (maximum
      14. 8). Most of these tumors were found incidentally, with a mean tumor diameter
      on ultrasound of 3.3 cm (range 1.0 to 8.6). RESULTS: The postoperative course was
      unremarkable in 173 patients. Postoperative bleeding was encountered in 4
      patients and urinary extravasation in an additional 3 patients. No surgical
      reintervention was necessary. One hundred seventy-five RCCs were pT1 and 5 were
      pT3a; 73 were grade 1, 100 grade 2, and 7 were grade 3. The mean tumor diameter
      (surgical specimen) was 3.2 cm (range 0.5 to 7). In 132 cases, the tumor was less
      than 4 cm and in 48 cases, greater than 4 cm. Three patients experienced local
      tumor recurrence (1.6%) during follow-up, and two others developed distant
      metastases. The 5-year tumor-specific survival rate was 98.0%. CONCLUSIONS:
      Nephron-sparing surgery for RCC under an elective indication in selected patients
      offers excellent long-term survival and an acceptably low local tumor recurrence
      rate. These results support the concept of nephron-sparing surgery in the
      presence of a normal contralateral kidney.

PMID- 10962301
TI  - Blood-based RT-PCR assays of MN/CA9 or PSMA: clinical application in renal cancer
      patients.
AB  - OBJECTIVES: To report a survey of blood-based RNAs obtained from common groups of
      control and renal cancer patients for expression of both MN/CA9 and prostate
      specific membrane antigen (PSMA) messenger RNAs. METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR) assays for MN/CA9 and PSMA were performed on
      RNAs extracted from 81 blood samples (59 patients with renal cancer, 7 with
      benign tumors, and 15 control volunteers). The results of these assays were
      statistically analyzed to determine whether a positive result (individually or
      combined) correlates with any tumor characteristics. RESULTS: Neither MN/CA9 nor
      PSMA amplification products were detected in the RNAs from peripheral blood
      samples of the 15 control volunteers and from the 7 patients with benign renal
      tumor (sensitivity 100%). MN/CA9 alone was detected in 11 (19%) of 59 samples and
      PSMA alone in 12 (20%) of 59 samples from patients with renal cancer. PSMA
      positivity was significantly correlated with vascular invasion of the primary
      tumor. Expression of one or both of these molecular tumor markers was detected in
      21 (36%) of 59 renal cancer patients. When combined, the results of the MN/CA9
      and PSMA RT-PCR tests were found to be highly associated with vascular invasion
      in nephrectomy specimens (sensitivity 67%, specificity 77%, odds ratio = 6.89, P
      = 0.002). CONCLUSIONS: Combination of RT-PCR assays for MN/CA9 and PSMA provides
      a sensitive blood test for molecular detection of clear cell carcinoma of the
      kidney and its potential for vascular invasion. Further testing of this assay
      will be required to evaluate its efficacy in the diagnosis, screening, and follow
      up of patients with kidney cancer.

PMID- 10962302
TI  - Second primary malignancies associated with renal cell carcinoma: influence of
      histologic type.
AB  - OBJECTIVES: This study was performed to determine which histologic types of renal
      cell carcinoma have an association with a second primary malignancy. METHODS:
      Seven hundred sixty-three patients underwent an operation for renal cell
      carcinoma between July 1989 and January 1999. The incidence of antecedent,
      synchronous, or subsequent second malignancies was determined. Statistical tests
      based on the Poisson model were used to compare the observed number of subsequent
      malignancies developing after a diagnosis of renal cell carcinoma with the
      expected number calculated using the 1973 to 1994 U.S. Surveillance,
      Epidemiology, and End Results age, race, gender, and calendar-year specific
      incidence rates. RESULTS: Second primary malignancies were present in 209 of 763
      (27.4%) patients, with prostate, breast, colon, and bladder cancer and non
      Hodgkin's lymphoma being the five most common second malignancies. The other
      malignancies were antecedent in 118 cases (44.5%), synchronous in 104 cases
      (39.2%), and subsequent in 43 cases (16.2%). Patients with papillary renal cell
      carcinoma were at increased risk of developing bladder cancer (standardized
      incidence ratio [SIR] 6.5, P = 0.038). Men with papillary renal cell carcinoma
      were also at increased risk of developing prostate cancer (SIR 2.8, P = 0.035).
      CONCLUSIONS: There is an increased risk of subsequent bladder and prostate cancer
      in patients with papillary renal cell carcinoma.

PMID- 10962303
TI  - High-frequency endoluminal ultrasonography for staging transitional cell
      carcinoma of the bladder.
AB  - OBJECTIVES: To assess the feasibility and limitations of endoluminal ultrasound
      (ELUS) for clinical staging of bladder tumors. METHODS: From 1998 to 1999, 32
      patients with transitional cell carcinoma of the bladder were evaluated by high
      frequency ELUS using miniature ultrasound transducers (20 MHz, 5.1F or 7.2F)
      before transurethral resection. Clinical staging using ELUS was compared with the
      results of pathologic staging. RESULTS: Seventeen (94%) of the 18 patients with
      superficial tumors on ELUS were confirmed by pathologic examination to have Stage
      pTa (n = 12) or Stage pT1 (n = 5) disease, and 11 (63%) of the 14 patients with
      muscle-invasive tumors on ELUS were confirmed by pathologic evaluation to have
      Stage pT2a (n = 2) or Stage pT2b (n = 9) disease. In all of the misdiagnosed
      patients, the tumor lacked a well-defined base and was larger than 2 cm in size.
      It was difficult to distinguish between Stage Ta and Stage T1 tumors because of
      the limited resolution of ELUS and between Stage T2a and Stage T2b tumors because
      of its low penetration. CONCLUSIONS: ELUS using a high-frequency (20 MHz),
      miniature ultrasound transducer is able to distinguish superficial tumors from
      those with muscle invasion. However, the lack of penetration of the sonographic
      beam places major limitations on the evaluation of the depth of the invasion in
      large (greater than 2 cm) tumors with a broad base.

PMID- 10962304
TI  - Noninvasive urodynamic evaluation of bladder outlet obstruction using Doppler
      ultrasonography.
AB  - OBJECTIVES: Previously we had developed a new method of noninvasive urodynamics
      using color Doppler ultrasound. Using this technique, we attempted to identify
      parameters that would diagnose bladder outlet obstruction (BOO). METHODS: Twenty
      two men who underwent pressure-flow urodynamic studies were included. Color scale
      transperineal ultrasound and uroflowmetry data were analyzed by custom-made
      software. The maximum flow velocities in the entire prostatic urethra (V(0)), in
      the distal prostatic urethra just proximal to the external urethral sphincter
      (V(1)), and in the membranous urethra (V(2)) were obtained. Corresponding
      functional cross-sectional areas of the urethra at these three sites (A(0), A(1),
      and A(2)) were calculated as Qmax/V. The velocity ratio (VR), which was equal to
      V(1)/V(2), was also calculated as a parameter. All these parameters obtained by
      the velocity-flow urodynamics were compared with the Abrams-Griffiths number
      (AG). RESULTS: From the x-y plots obtained, VR correlated best with AG, with
      Spearman's rho of 0. 728. A(0) and A(1) had rho values of -0.461 and -0.708
      against AG, respectively. All men with VR exceeding 1.6 had obstruction, whereas
      those with VR less than 1.1 did not. CONCLUSIONS: The VR was found to be the best
      parameter for diagnosing BOO. When prostatic urethral obstruction was present,
      the velocity in the prostatic urethra would be high but the velocity slows down
      to 62.5% or greater immediately below the sphincter. We believe that noninvasive
      pressure-flow-like urodynamic evaluation based on Doppler ultrasound has clear
      potential for diagnosing BOO.

PMID- 10962306
TI  - Predicting the outcome of prostate biopsy in screen-positive men by a multilayer
      perceptron network.
AB  - OBJECTIVES: To assess whether an artificial neural network (multilayer
      perceptron, MLP) and logistic regression (LR) could eliminate more false-positive
      prostate-specific antigen (PSA) results than the proportion of free PSA in a
      prostate cancer screening. METHODS: MLP and LR models were constructed on the
      basis of data on total PSA, the proportion of free PSA, digital rectal
      examination (DRE), and prostate volume from 656 consecutive men (aged 55 to 67
      years) with total serum PSA concentrations of 4 to 10 ng/mL in the randomized
      population-based prostate cancer screening study in Finland. The MLP and LR
      models were validated using the "leave-one-out" method. RESULTS: Of the 656 men,
      23% had prostate cancer and 77% had either normal prostatic histology or a benign
      disease. At a 95% sensitivity level, 19% of the false-positive PSA results could
      be eliminated by using the proportion of free PSA versus 24% with the LR model
      and 33% with the MLP model (P < 0.001). At 80% to 99% sensitivity levels, the
      accuracy of the MLP and LR models was significantly higher than that of the
      proportion of free PSA. At 89% to 99% sensitivities, the accuracy of the MLP was
      higher than that of LR (P </= 0.001). CONCLUSIONS: At clinically relevant
      sensitivity levels, the MLP and LR models based on total PSA, the proportion of
      free PSA, DRE, and prostate volume could reduce the number of unnecessary
      biopsies significantly better than the proportion of free PSA alone in men with
      total PSA levels in the range 4 to 10 ng/mL.

PMID- 10962305
TI  - Pentosan polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic
      pain syndrome category IIIA): a prospective multicenter clinical trial.
AB  - OBJECTIVES: Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS)
      has clinical and perhaps etiologic characteristics similar to interstitial
      cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the
      treatment of interstitial cystitis, has shown moderate benefit in reducing
      chronic pelvic pain and voiding symptoms in patients with interstitial cystitis.
      We undertook a prospective open-label, multicenter Phase II pilot study to
      examine the potential efficacy of PPS in the treatment of CPPS in men, using
      outcome tools validated for CPPS in men. METHODS: Patients with a diagnosis
      consistent with National Institutes of Health (NIH) CPPS category IIIA
      (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The
      evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity
      Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom
      Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global
      assessment. RESULTS: Thirty-two patients (mean age 45.5 +/- 11 years; duration of
      symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were
      available for evaluation. Seven patients experienced drug-related side effects,
      including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight
      gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom
      Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to
      36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to
      9.2) symptom scores at 6 months compared with baseline was significant. The
      decrease was associated with a significant improvement in patients' quality of
      life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients
      had a greater than 50% improvement in the Symptom Frequency Questionnaire,
      Symptom Severity Index, and NIH-CPSI (rated as clinically significant
      improvement). At 6 months, mild, moderate, and marked improvement was noted
      (subjective global assessment) by 33%, 19%, and 15% of the patients,
      respectively. CONCLUSIONS: PPS is well tolerated and appears to have efficacy in
      reducing the severity and frequency of general symptoms, reducing specific pain
      symptoms, and improving the quality of life in many male patients with CPPS. The
      results of this study justify the initiation of a randomized controlled trial
      comparing the safety and efficacy of PPS to placebo.

PMID- 10962307
TI  - Correlation of preoperative plasma IGF-I levels with pathologic parameters and
      progression in patients undergoing radical prostatectomy.
AB  - OBJECTIVES: To test whether preoperative insulin-like growth factor (IGF)-I
      levels could predict pathologic stage and prognosis of prostate cancer in
      patients undergoing radical prostatectomy. METHODS: The study group consisted of
      120 consecutive patients who underwent radical prostatectomy for clinically
      localized prostate cancer. Preoperative plasma IGF-I levels were measured using
      the DSL-IGF-I Elisa assay. Surgically removed prostate specimens were analyzed
      pathologically, using a whole-mount step-section technique. Preoperative plasma
      IGF-I levels were compared with final pathologic parameters and with prostate
      specific antigen (PSA) progression-free survival. Preoperative IGF-I levels in
      this cohort were also compared with IGF-I levels measured in 20 healthy men
      without any cancer and in 10 men with untreated, metastatic prostate cancer.
      RESULTS: Plasma IGF-I levels predicted neither organ-confined disease (P =
      0.5611) nor the risk of PSA progression (P = 0.8125) at a median follow-up of
      48.6 months after prostatectomy. Furthermore, IGF-I levels did not correlate with
      preoperative PSA level (P = 0. 2811) or final Gleason score (P = 0.4906). IGF-I
      levels in radical prostatectomy patients were not significantly higher than those
      in healthy subjects or in patients with metastatic disease (mean 156.7 +/- 66
      ng/mL, 148.6 +/- 49 ng/mL, and 148.6 +/- 93 ng/mL, respectively; P = 0.8442).
      CONCLUSIONS: Circulating IGF-I levels may predict the future risk of developing
      prostate cancer, but our study found no association with other established
      markers of biologically aggressive disease or with disease progression in
      patients with clinically localized prostate cancer.

PMID- 10962308
TI  - Does the completeness of prostate sampling predict outcome for patients
      undergoing radical prostatectomy?: data from the CAPSURE database.
AB  - OBJECTIVES: To determine whether more complete sampling of the radical
      prostatectomy (RP) specimen better predicts outcome after surgery. METHODS: We
      reviewed pathology reports from 1383 patients enrolled in CaPSURE (a longitudinal
      registry of patients with prostate cancer) who underwent RP. Specimens were
      considered step-sectioned only if the entire specimen was submitted for analysis
      and if sections were taken at 0.5-cm intervals or less. Otherwise, specimens were
      considered non-step-sectioned. Pathologic stage, Gleason score, surgical margin
      status, and outcome were compared between groups. Prostate-specific antigen (PSA)
      recurrence was defined as a PSA level of 0.2 ng/mL or greater on two consecutive
      occasions after RP. Secondary cancer treatment consisted of radiation or androgen
      deprivation after RP. Adjuvant treatments occurred within 6 months of RP, and
      nonadjuvant treatments occurred more than 6 months after RP. Kaplan-Meier event
      rates of PSA recurrence and secondary treatment were calculated for patients in
      the step-sectioned and non-step-sectioned groups. RESULTS: No significant
      differences were found between patients in the step-sectioned and non-step
      sectioned groups with respect to pathologic tumor stage, prostatectomy Gleason
      score, or margin status. Patients in whom step-sectioning was performed had a
      lower serum PSA at diagnosis than patients in the non-step-sectioned group. When
      examining all patients, no differences were observed in the use of secondary
      treatments or PSA recurrence based on the method of pathologic analysis. However,
      patients with negative margins in whom step-sectioning was performed exhibited
      significantly lower secondary nonadjuvant treatment use and appeared to have a
      lower risk of PSA recurrence than similar patients in the non-step-sectioned
      group. CONCLUSIONS: These data suggest that more complete pathologic analysis of
      the surgical specimen may better predict outcome for some patients undergoing RP.
      Additional research is warranted to determine whether such differences justify
      the additional resources necessary to recommend routine step-sectioning.

PMID- 10962309
TI  - Fifteen-year minimum follow-up of a prostate brachytherapy series: comparing the
      past with the present.
AB  - OBJECTIVES: To report the overall survival for 126 patients more than 15 years
      after iodine-125 interstitial therapy; to report the biochemical progression
      status for those alive and clinically without evidence of disease for longer than
      15 years; to document the upward migration of grade by date of grade assignment;
      to compare the tumor stage and grade profile of this mature series with our
      current experience; and to clarify the prostate-specific antigen (PSA) data when
      this series is used as a historical comparison. METHODS: The records of 126
      patients who underwent interstitial therapy more than 15 years previously were
      reviewed for assessment of the current TNM stage and Gleason grade and the
      current PSA level for patients clinically free of disease. The tumor grade and
      stage of these patients were compared with those of the first 126 patients
      treated by transrectal ultrasound-guided brachymonotherapy at our center between
      January 1995 and January 1999. The methodology of our 1993 publication was also
      reviewed. RESULTS: Of the 16 patients clinically free of disease (13 still alive
      and 3 dead of other causes more than 15 years after therapy), a review of the
      initial diagnostic needle biopsy was unable to confirm the presence of tumor in 3
      patients. Of the remaining 13, 4 had a PSA level of 0.2 ng/mL or less, 4 a PSA
      level between 0.21 and 0.9 ng/mL, and 5 a PSA level between 1 and 2.5 ng/mL. Re
      evaluation of the histopathologic findings using current criteria increased the
      Gleason score and World Health Organization grade. Patients currently selected
      for brachytherapy have a lower Gleason grade and TNM stage than recorded for
      patients treated in the past. The actuarial progression probability curves using
      the 0.5 or less cutpoint published in 1993 represented the best possible outcome
      and cannot serve as a historical control for current series comparisons.
      CONCLUSIONS: For patients who were alive and clinically free of disease longer
      than 15 years after therapy, the biochemical PSA levels were low. This may be
      attributed to the therapeutic radiation effect. Whether the improved technology
      of current transrectal ultrasound-guided implants can extend these favorable
      results from a small minority to a significant majority and whether it can
      approach the therapeutic results of radical prostatectomy may be partially
      answered with a longer follow-up of the current series. The histopathologic
      criteria have been refined, and upgrading from the initially assigned grade is
      common. In some cases, a prostate cancer diagnosis could not be confirmed. These
      findings limit the ability to match patients across time and institution. The
      results of our 1993 report of biochemical chemical progression-free probability
      10 years after iodine-125 implantation cannot be used as a comparator for current
      studies. Ultimately, a valid comparison between treatment options will only be
      achieved through a randomized controlled trial.

PMID- 10962310
TI  - Fifteen-year minimum follow-up of a prostate brachytherapy series: comparing the
      past with the present.

PMID- 10962311
TI  - Fifteen-year minimum follow-up of a prostate brachytherapy series: comparing the
      past with the present.

PMID- 10962312
TI  - Long-term survival in a Swedish population-based cohort of men with prostate
      cancer.
AB  - OBJECTIVES: To study the long-term survival of patients with prostate cancer,
      determine the risk factors for prostate cancer death, and investigate the outcome
      of initially untreated localized prostate cancer and incidentally detected
      tumors. METHODS: The survival of 813 patients in a population-based cohort of
      patients with prostate cancer in Linkoping, Sweden, diagnosed from 1974 to 1986,
      was analyzed. RESULTS: At 10, 15, and 20 years after diagnosis, the prostate
      cancer-specific survival rate of men with localized, initially untreated,
      prostate cancer was 85.0% (95% confidence interval [CI], 79.0% to 91.0%), 80.0%
      (95% CI, 72.5% to 87.5%), and 62.6% (95% CI, 43.0% to 82.2%). Age 70 years or
      older, advanced stage, and poor differentiation were risk factors associated with
      an increased risk of prostate cancer death. At 10 years, the prostate cancer
      specific survival rate among men with localized tumors treated by expectancy was
      90% (95% CI, 84% to 97%) for grade 1 tumors, 74% (95% CI, 60% to 89%) for grade 2
      tumors, and 59% (95% CI, 29% to 90%) for grade 3 tumors. For patients with
      incidentally detected tumors, the grade of malignancy was a more important risk
      factor than tumor volume. CONCLUSIONS: Patients with localized tumors have a
      favorable prognosis, even without initial treatment. However, when deciding on
      therapy, the grade of malignancy should be taken into account, as it has a great
      influence on survival. We did not see a tendency toward increased mortality when
      the patients were followed up for longer than 10 years after diagnosis.

PMID- 10962313
TI  - Bladder neck involvement at radical prostatectomy: positive margins or advanced
      T4 disease?
AB  - OBJECTIVES: To assess the prognosis of patients with bladder neck (BN)
      involvement in radical prostatectomy specimens and compare it with patients with
      seminal vesicle invasion (SVI) presumed to have an inferior stage according to
      the TNM classification. METHODS: Two hundred eighty-six case files of consecutive
      radical prostatectomies were reviewed. The records of patients with pathologic BN
      involvement (pT4a) or SVI (pT3c) were thoroughly analyzed and compared. The mean
      and median follow-up periods were 30.8 and 35.5 months (range 9 to 40),
      respectively, for the patients with Stage pT4a and 40.8 and 44.1 months (range 8
      to 86), respectively, for the patients with Stage pT3c. Particular attention was
      paid to the preoperative clinical and pathologic evaluation, the pathologic
      analysis of the prostatectomy specimen, and the postoperative follow-up data.
      Progression was defined as a prostate-specific antigen level of 0.2 ng/mL and
      rising. Adjuvant therapy was not initiated unless prostate-specific antigen
      failure had occurred. RESULTS: BN involvement was identified in 25 patients
      (8.7%) and SVI was found in 26 patients (9.1%). In 7 patients (2.4%), the BN was
      the only site of positive margins. Thirty-six percent of patients with BN
      involvement and 62% of patients with SVI demonstrated biochemical progression.
      Disease-free survival and metastasis-free survival rates were significantly
      better for the patients with Stage pT4a than for the patients with Stage pT3c at
      24 and 36 months after surgery. Univariate analysis identified the prostate
      specific antigen nadir to be the most significant predictor of prognosis.
      CONCLUSIONS: In this study, BN involvement in the surgical specimen carried a
      lower risk of progression than SVI. On the basis of our preliminary results and
      those in other studies, a conceivable downstaging of BN involvement in the TNM
      staging system should be considered. Possibly, additional modification of the TNM
      staging system should be contemplated on the basis of the results of pathologic
      analysis and prognosis. The significance of BN involvement and the role of
      adjuvant therapy in this group of patients need further evaluation.

PMID- 10962314
TI  - Update on impact of moderate dose of adjuvant radiation on urinary continence and
      sexual potency in prostate cancer patients treated with nerve-sparing
      prostatectomy.
AB  - OBJECTIVES: Adjuvant radiotherapy to the prostatic bed at moderate doses of 45 to
      54 Gy achieves results comparable to higher doses. We studied the effect of
      moderate doses of postoperative radiation therapy on urinary continence and
      sexual potency in prostate cancer patients who had undergone nerve-sparing
      prostatectomy. METHODS: Between November 1983 and December 1992, 255 prostate
      cancer patients were selected to undergo nerve-sparing prostatectomy. A total of
      94 (37%) patients had received adjuvant postoperative radiotherapy, 45 to 54 Gy
      to the prostatic bed, based on microscopic positive margins, seminal vesicle
      involvement, and/or Gleason score. Subjective patient reports regarding the
      potency and urinary continence status were recorded during a semistructured
      telephone interview at 3 or more years after treatment. The findings in
      irradiated and nonirradiated patients were compared and correlated to those
      obtained from the same patients preoperatively and 1 year postoperatively.
      RESULTS: At 3 or more years of follow-up no significant difference among
      irradiated and nonirradiated patients was detected. Most patients described
      optimal urinary continence and approximately one third had maintained potency
      after bilateral nerve-sparing prostatectomy. None of the patients who had
      undergone unilateral nerve-sparing surgery remained potent. Using a multivariable
      analysis, the significant predictors for maintaining potency were the status at 1
      year postoperatively and bilateral versus unilateral nerve-sparing procedure.
      CONCLUSIONS: Doses of adjuvant radiation therapy in the range used (45 to 54 Gy)
      did not affect the long-term pattern of maintenance of either function.

PMID- 10962315
TI  - Is scrotal violation per se a risk factor for local relapse and metastases in
      stage I nonseminomatous testicular cancer?
AB  - OBJECTIVES: To determine the risk of local recurrence and relapse in patients
      with Stage I nonseminomatous testicular cancer with scrotal violation. METHODS:
      From 1983 to 1998, 75 patients with clinical Stage I nonseminomatous testicular
      cancer who were initially treated with orchiectomy and surveillance alone were
      retrospectively reviewed. RESULTS: Of 75 patients with Stage I nonseminomatous
      testicular cancer, 13 had scrotal violation. The surgical margins and the
      spermatic cords were free of tumor in all patients. Five patients (38%) in the
      scrotal violation group and 17 patients (27%) in the inguinal orchiectomy group
      experienced relapses. The difference was not significant (P = 0.41). Local
      recurrence was not observed in either group. All relapses, except one in the
      standard inguinal orchiectomy group, were treated successfully with chemotherapy
      and postchemotherapy surgery, if needed. The progression rate and survival were
      not significantly different between the two groups. CONCLUSIONS: Scrotal
      violation without positive surgical margins and tumor spillage does not adversely
      affect relapse rate and survival. Therefore, scrotal violation per se is not an
      exclusion criterion for the surveillance-only policy in patients with Stage I
      nonseminomatous testicular germ cell cancer.

PMID- 10962316
TI  - Smoking is associated with the retention of cytoplasm by human spermatozoa.
AB  - OBJECTIVES: To determine whether cigarette smoking is associated with the
      abnormal retention of residual sperm cytoplasm in infertile men. METHODS: Semen
      samples were obtained from 87 consecutive non-azoospermic men with idiopathic
      infertility (18 smokers and 69 nonsmokers) and from 20 men presenting for
      vasectomy (fertile controls). Standard semen parameters and the percentage of
      spermatozoa with residual cytoplasm (on Papanicolaou smears) were recorded.
      RESULTS: Subject age, semen volume, and sperm density, motility, and morphology
      were not significantly different between the two groups of infertile men.
      However, a significant difference was found in the mean +/- SEM percentages of
      sperm with cytoplasm droplets between smokers and nonsmokers (12.9% +/- 1.7% and
      8.1% +/- 0.9%, respectively; P < 0.001). CONCLUSIONS: Our data suggest that
      cigarette smoking is associated with retention of sperm cytoplasmic droplets in
      infertile men, a morphologic characteristic associated with impaired sperm
      function.

PMID- 10962317
TI  - Recurrence of germ cell tumor after orchiectomy.
AB  - OBJECTIVES: To assess the characteristics of patients with recurrent disease by a
      retrospective analysis. METHODS: Between 1982 and 1998, 488 patients were treated
      in Nijmegen for testicular cancer. All patients underwent orchiectomy and
      adjuvant treatment when indicated. Patients were routinely followed up. RESULTS:
      In 36 patients (7.4%), disease recurrence was found during follow-up; 12 had
      contralateral disease and 24 systemic recurrence. Contralateral testicular cancer
      occurred a median of 63.8 months (range 43.2 to 165.2) after orchiectomy and
      systemic recurrence at a median of 6.1 months (range 1.5 to 94.4). Contralateral
      testicular cancer was more frequent in patients with pure seminoma (odds ratio
      4.3, 95% confidence interval 1.4 to 13.1); 8 of 9 patients with contralateral
      cancer received adjuvant radiotherapy. The best predictor of systemic recurrence
      after nonseminoma germ cell tumor was the presence of teratoma and embryonal cell
      components in the primary tumor. In the entire population, 19 patients (3.9%)
      died of the disease. None of the patients with contralateral testicular
      recurrence or systemic recurrence after Stage I seminoma died of the disease. One
      of 10 patients died of recurrent Stage I nonseminoma germ cell tumor. The chance
      of dying of recurrence after metastatic nonseminoma germ cell tumor was 36%.
      CONCLUSIONS: Recurrence after an initially complete response is rare in
      testicular cancer. Contralateral testicular cancer is associated with the
      presence of seminoma components in the primary tumor and occurs almost 10 times
      later than systemic recurrence. The prognosis after contralateral testicular
      cancer and after recurrence in Stage I seminoma is good.

PMID- 10962319
TI  - Relationship between patient self-assessment of erectile function and the
      erectile function domain of the international index of erectile function.
AB  - OBJECTIVES: To assess the validity of severity classes on the erectile function
      (EF) domain of the International Index of Erectile Function by determining their
      relationship with the self-assessment of EF, before and after treatment, in an
      independent cohort of patients. METHODS: Two hundred forty-seven men with
      clinically diagnosed erectile dysfunction (ED) and in a stable heterosexual
      relationship were enrolled in a randomized, double-blind, multicenter, placebo
      controlled, parallel-group, 12-week, flexible-dose study. Patients assessed their
      degree of ED as severe, moderate, minimal/mild, or no problem at baseline and
      after treatment. They also responded to the six questions of the EF domain, with
      the total score indicating the following degrees of ED: severe, EF score 1 to 10;
      moderate, EF score 11 to 16; mild to moderate, EF score 17 to 21; mild, EF score
      22 to 25; and no ED, EF score 26 to 30. Descriptive profiles of the two
      diagnostic instruments were compared. The correlations between the instruments
      were evaluated with Kendall's tau-b at baseline, after treatment at 12 weeks, and
      at change from baseline. RESULTS: The two measures gave generally similar
      descriptive profiles of ED severity. The correlations were 0. 65 (95% confidence
      interval 0.57 to 0.73) at baseline, 0.86 (95% confidence interval 0.83 to 0.89)
      after 12 weeks of treatment, and 0. 73 (95% confidence interval 0.67 to 0.79) at
      change from baseline. CONCLUSIONS: The moderate-to-high correlation between the
      patients' self-assessment of EF and the EF domain of the International Index of
      Erectile Function provides a validation of this domain for the reliable
      diagnostic classification of ED severity.

PMID- 10962318
TI  - Side-effect profile of sildenafil citrate (Viagra) in clinical practice.
AB  - OBJECTIVES: Sildenafil citrate (Viagra) has been shown to be an effective
      treatment for erectile dysfunction. Initial studies reported a high tolerability
      and low incidence of certain characteristic adverse reactions. We sought to
      evaluate the incidence of side effects of sildenafil citrate, independent of
      industry support and constraints, utilizing a heterogeneous cohort of patients
      from a university-based practice. METHODS: A prospective, open-label, flexible
      dose study of 256 patients treated with sildenafil citrate for erectile
      dysfunction was performed at a single institution. The patients were questioned
      explicitly about the occurrence of headache, flushing, dyspepsia, nasal
      congestion, visual changes, and other side effects. RESULTS: The adverse
      reactions most commonly observed were flushing (30.8%), headache (25. 4%), nasal
      congestion (18.7%), and heartburn (10.5%). All events were short lived and mild
      in nature. In the present study, 31.6% of patients experienced one or more
      adverse events. However, no one withdrew from the study because of the severity
      of these events. There was a significant association between higher doses and the
      occurrence of side effects. CONCLUSIONS: The incidence of adverse events
      attributable to sildenafil citrate may be higher than initially reported, but an
      explanation may be the methodology of data collection and the industry
      independent nature of this study. The side-effect profile is dose related and
      mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile
      dysfunction.

PMID- 10962320
TI  - Bladder calculi in augmentation cystoplasty in children.
AB  - OBJECTIVES: To determine the best preventive strategies for bladder calculi in
      children with an augmented bladder, the risk factors and prevention strategies
      for urolithiasis were evaluated. METHODS: The records of 89 patients following
      augmentation cystoplasty were reviewed to assess the results of augmentation
      cystoplasties and in particular the formation and prevention of calculi. RESULTS:
      The median follow-up was 4.9 years after augmentation. Most patients (71) had an
      ileocystoplasty. Bladder calculi occurred in 14 of the 89 patients (16%) and
      recurred in 4 patients. Girls had a higher incidence of urolithiasis. Other risk
      factors were cloacal malformations, vaginal reconstructions, anal atresia, clean
      intermittent catheterization problems and retention, bladder neck surgery, and
      symptomatic urinary tract infections. CONCLUSIONS: Subgroups with cloacal
      malformations, vaginal reconstructions, ureter reimplantation, and bladder neck
      surgery were identified that have an increased risk for stone formation and
      therefore warrant special care in the follow-up after augmentation. This care
      should include clear emphasis on the role of treating symptomatic urinary tract
      infections, especially in patients with cloacal malformations and vaginal
      reconstructions. Girls have a higher incidence of bladder calculi than boys.

PMID- 10962321
TI  - Radical cystectomy: minimizing operative blood loss with a "stapling technique".
AB  - We describe our experience with a surgical technique using the multiple fire Endo
      GIA-30-3.5 stapler to control the vascular pedicles during radical cystectomy.
      This technique was performed in 16 radical cystectomies, including three pelvic
      anterior exenterations for female invasive bladder carcinoma, and compared with
      23 cases treated with the conventional method. It was associated with a
      significant decrease in the intraoperative and postoperative blood loss and a
      shorter operative time.

PMID- 10962322
TI  - Intraoperative treatment planning for radioactive seed implant therapy for
      prostate cancer.
AB  - We describe a procedure for intraoperative treatment planning for seed
      implantation. One hundred seven treatment plans have been analyzed at the Beth
      Israel Deaconess Medical Center and affiliated hospitals. The average time for
      the intraoperative procedure was 1. 74 hours. No significant difference in dose
      coverage to the prostate or normal tissues was evident.

PMID- 10962323
TI  - An atraumatic anatomic technique for separation of the pediatric hernia sac from
      the spermatic cord.
AB  - A detailed photographically illustrated anatomic technique for the sequential
      dissection of the pediatric hernia sac from the spermatic cord has not been
      described. An illustrated technique to atraumatically dissect the hernia sac in a
      systematic fashion is therefore presented.

PMID- 10962324
TI  - In situ vaginal wall sling.
AB  - INTRODUCTION: Recent reviews have noted failures of transvaginal surgical
      procedures designed to cure female stress urinary incontinence (SUI). Slings for
      SUI appear to sustain continence over time but have been reserved for the more
      complex cases of intrinsic sphincteric deficiency because of the perception by
      many surgeons of increased technical difficulty and complication rates. However,
      this very success in complex cases of SUI bespeaks the need to develop
      modifications to simplify sling surgery so as to encourage sling use in all women
      with SUI. Modifications continue to be applied, including anchoring the
      supporting sutures to the pelvic bones and reducing the transvaginal dissection
      to prevent further prolapse. I review the use of the in situ anterior vaginal
      wall sling using bone anchoring techniques with preservation of the endopelvic
      fascia. TECHNICAL CONSIDERATIONS: The in situ sling is performed with the patient
      in the dorsal lithotomy position under regional or general anesthesia, with a 16F
      Foley catheter placed in the bladder and a weighted vaginal speculum on the
      posterior vaginal wall. An anterior vaginal suburethral patch is supported by
      nonabsorbable sutures anchored to the pubic bone. CONCLUSIONS: The use of bone
      anchoring techniques with preservation of the endopelvic fascia appears to
      enhance the success rate of autologous vaginal wall slings without increasing the
      risk to the patient and, as minimally invasive procedures, these techniques
      appear to reduce surgical time and length of hospitalization, thus reducing
      costs.

PMID- 10962325
TI  - Ileal conduit staple reflux: a nidus for renal calculi.

PMID- 10962326
TI  - Importance of a filled bladder for the detection of intravesical pathologic
      features.

PMID- 10962327
TI  - Focal lobular spermatogenesis and pubertal acceleration associated with
      ipsilateral Leydig cell hyperplasia.
AB  - Leydig cell tumors of the testis are the underlying cause in about 10% of the
      cases of precocious puberty in boys. Leydig cell hyperplasia is a less well
      characterized cause, with an undocumented frequency. We describe a boy with
      precocious puberty associated with ipsilateral testicular enlargement and focal
      Leydig cell hyperplasia with spermatogenesis limited to the local adjacent
      testicular tissue.

PMID- 10962328
TI  - Carcinosarcoma of the renal pelvis.
AB  - Carcinosarcoma of the renal pelvis is a rare neoplasm, with 7 cases reported.
      This lesion should be differentiated from a sarcomatoid variant of renal cell
      carcinoma; it is usually associated with a poor prognosis. We report an
      additional case of renal pelvic carcinosarcoma.

PMID- 10962329
TI  - Calculus-producing and cytomegalovirus-infected nephrogenic adenoma of the
      bladder in a prepubertal renal transplant recipient.
AB  - A 14-year-old prepubertal boy, a renal transplant recipient, was treated for a
      nephrogenic adenoma. His case is unique in that he is the second youngest renal
      transplant recipient diagnosed with a nephrogenic adenoma. In addition, the
      lesion was calculus producing, which has not been previously described, and
      contained cytomegalovirus inclusions, which has been described only once
      previously in association with a nephrogenic adenoma in a transplant patient.

PMID- 10962330
TI  - Endourologic treatment of nephrocalcinosis.
AB  - Calcifications of the kidney may be located free within the collecting system,
      attached to a papilla, trapped beneath the urothelium, or sequestered in the
      renal parenchyma. Extracorporeal shock wave lithotripsy has failed to render
      patients who presented with nephrocalcinosis stone free because of the submucosal
      location of some of the calculi. We report a unique case of symptomatic
      nephrocalcinosis in which the patient was rendered stone free using flexible
      ureteroscopy and intrarenal laser and electrohydraulic lithotripsy to treat both
      the attached and submucosal papillary calculi.

PMID- 10962331
TI  - Adrenal ganglioneuroma: a familial case.
AB  - A 67-year-old woman was evaluated for asymptomatic microscopic hematuria.
      Intravenous urography and computed tomography demonstrated an adrenal mass, but
      the workup for a functional adrenal tumor was negative. The mass was surgically
      resected, with a histologic diagnosis of adrenal ganglioneuroma. No further
      treatment was necessary. After the diagnosis was made, the patient reported a
      family history positive for neuroblastic tumors. Two of her grandchildren had
      presented at early ages with a ganglioneuroblastoma and a third had presented
      with a ganglioneuroma. This presentation is unique because ganglioneuroma,
      especially that of adrenal origin, is rare in the adult population, and familial
      cases are extremely uncommon.

PMID- 10962332
TI  - Life-threatening anaphylactoid reaction associated with indigo carmine
      intravenous injection.
AB  - Indigo carmine (sodium indigotindisulfonate), a blue dye, has been widely used by
      surgeons to identify and to examine the urinary tract and is considered
      biologically inert and extremely safe. We present a case of severe life
      threatening anaphylactoid reaction followed by cardiac arrest associated with
      intravenous indigo carmine injection.

PMID- 10962333
TI  - Posterior urethral disruption secondary to a penetrating gluteal injury.
AB  - We report a case of a complete posterior urethral injury secondary to a
      penetrating gluteal injury. Posterior urethral injury usually occurs in male
      patients with pelvic trauma. The reported incidence of urethral injury with
      pelvic fracture ranges from 1.6% to 25% (mean 10%), with 66% of them being
      complete posterior urethral ruptures. Causes of posterior urethral disruptions
      include blunt trauma, such as occur in road traffic accidents or falls from
      heights, and high velocity penetrating and crush injuries. Penetrating gluteal
      injuries that cause posterior urethral damage are extremely rare. This report
      presents the first case of a complete urethral injury due to a gluteal stab
      wound. Furthermore, this case demonstrates that any sign of injury to the lower
      urinary tract, regardless of the cause or weapon implicated, warrants an
      immediate evaluation.

PMID- 10962334
TI  - Megalophallus as a sequela of priapism in sickle cell anemia: use of blood oxygen
      level-dependent magnetic resonance imaging.
AB  - Priapism is a common complication of sickle cell anemia. We report a little known
      sequela of priapism: painless megalophallus, with significant penile enlargement.
      The patient had had an intense episode of priapism 9 years previously and his
      penis remained enlarged. Blood oxygen level-dependent magnetic resonance imaging
      revealed enlarged, hypoxic corpora cavernosa. Megalophallus probably resulted
      from permanent loss of elasticity of the tunica albuginea due to severe
      engorgement during the episode of priapism. This sequela needs to be recognized
      by physicians because no intervention is necessary and sexual function seems to
      remain intact.

PMID- 10962335
TI  - Cell proliferation and apoptosis with BCL-2 expression in renal cell carcinoma.
AB  - OBJECTIVES: To investigate cell proliferation, apoptosis, and bcl-2
      immunoreactivity in renal cell carcinoma (RCC). METHODS: Formalin-fixed and
      paraffin-embedded tissue blocks from 70 patients with RCC were studied. Cell
      proliferation activity was detected by Ki-67 immunostaining and the proliferation
      index (PI) was expressed as a percentage of the Ki-67-positive cells in the tumor
      cells. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated
      dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed
      as a percentage of the TUNEL-positive cells in the tumor cells. Immunoreactivity
      of bcl-2 was assessed immunohistochemically and coexpression of Ki-67 with bcl-2
      was examined by double immunostaining. RESULTS: The PI ranged from 5.0% to 44.0%
      (median 19.23%) and the AI from 0.9% to 3.4% (median 2.13%) in RCC. Statistical
      analysis revealed close associations between PI and tumor grade and stage, and a
      significant relationship between AI and the tumor grade of RCC. The expression of
      bcl-2 was detected in 24 (34.3%) of 70 RCCs. Coexpression of Ki-67 with bcl-2 was
      noted in 3 of the 24 RCCs with bcl-2 expression. The expression of bcl-2 was not
      related to PI, AI, or the clinicopathologic factors of RCC. CONCLUSIONS: Our
      observations suggest that active cell proliferation may be accompanied by
      frequent apoptosis and that cell proliferation as reflected by Ki-67 staining may
      be the most important parameter of cell turnover in RCC.

PMID- 10962336
TI  - Apoptosis in bladder carcinomas detected with monoclonal antibody to single
      stranded DNA: relation to cell cycle regulators and survival.
AB  - OBJECTIVES: To investigate the incidence of baseline apoptosis in relation to
      p27(Kip1), p53, and p21(Cip1) expression, proliferation status, standard
      clinicopathologic parameters, and patient outcome. Cell cycle regulators and
      apoptotic cell death have been implicated in tumor aggressiveness in many human
      malignancies. Their interaction, however, in the prognosis of patients with
      transitional cell carcinoma (TCC) of the urinary bladder has not yet received
      intense scrutiny. METHODS: Apoptotic fractions were quantified
      immunohistochemically by means of a novel monoclonal antibody recognizing single
      stranded DNA regions in apoptotic nuclei in 103 paraffin-embedded primary TCC
      specimens. Proliferative activity was expressed as the percentage of Ki-67
      positive cells (Ki-67 index). Tissue specimens were also stained for p27(Kip1),
      p53, and p21(Cip1) proteins. Patients were followed up until death (n = 30) or
      for an average of 40 months (median 36). RESULTS: The apoptotic index increased
      with grade, T stage, nonpapillary status, proliferative activity, and p53
      expression and was inversely related to p27(Kip1) and independently to p21(Cip1)
      expression. A negative correlation was found between p27(Kip1) expression and
      proliferation. The increased apoptotic index had an adverse impact on overall and
      disease-free survival (univariate analysis) and, along with T stage, was an
      independent predictor in muscle-invasive TCC. CONCLUSIONS: An increased apoptotic
      rate, increased proliferative activity, and decreased p21(Cip1) expression are
      independently interrelated in TCC. More importantly, the assessment of apoptotic
      potential appears to be more informative than standard prognosticators in
      predicting overall survival in patients with muscle-invasive TCC.

PMID- 10962338
TI  - Decreased concentrations of prostate-specific antigen and human glandular
      kallikrein 2 in malignant versus nonmalignant prostatic tissue.
AB  - OBJECTIVES: To study quantitatively the relative expression of human glandular
      kallikrein 2 (hK2) and prostate-specific antigen (PSA) in paired (from the same
      patient) cancerous and noncancerous prostatic tissue to evaluate whether these
      proteins are overexpressed or underexpressed in cancer. METHODS: We studied 14
      patients who underwent radical retropubic prostatectomy for prostate cancer.
      Cancerous and adjacent normal tissues were excised and then extracted to prepare
      cytosolic extracts. The extracts were analyzed for total protein, and for hK2 and
      PSA using sensitive and specific immunofluorometric procedures. RESULTS: PSA was
      present in the prostatic extracts at about 50 to 100 times higher amounts than
      hK2. The correlation between PSA and hK2 values was good. Both prostate
      kallikreins were expressed more in noncancerous than in cancerous prostatic
      tissue. CONCLUSIONS: Our results demonstrated that both PSA and hK2 are down
      regulated in prostate cancer compared with noncancerous tissue. The degree of
      down-regulation was higher for PSA than for hK2. The mechanism and physiologic
      consequences of this down-regulation are unknown.

PMID- 10962337
TI  - Efficacy of antiangiogenic therapy with TNP-470 in superficial and invasive
      bladder cancer models in mice.
AB  - OBJECTIVES: To evaluate the efficacy of antiangiogenic therapy with O
      (chloracetyl-carbamoyl) fumagillol (TNP-470) in a superficial and an invasive
      bladder cancer model in mice. The control of recurrent superficial and metastatic
      bladder cancer constitutes a major problem in urologic practice. Although the
      established therapies for these cases (immunotherapy, chemotherapy, and radiation
      therapy) have improved during the previous decades, further improvement and the
      reduction of existing side effects are needed. The inhibition of angiogenesis
      represents a new concept in cancer therapy. METHODS: We evaluated the in vitro
      effect of TNP-470 on the proliferation of bovine capillary endothelial cells
      (BCE), the superficial transitional cell carcinoma (TCC) cell line (KK-47), and
      the invasive TCC cell line (MGH-U1). To evaluate the in vivo effect of TNP-470 on
      the growth of advanced TCCs, both cell lines were injected subcutaneously into
      SCID mice. When tumors grew to a size of 100 to 200 mm(3), therapy either with
      TNP-470 or phosphate-buffered saline was initiated. RESULTS: TNP-470 strongly
      inhibited endothelial cell proliferation in vitro. The in vitro proliferation of
      both bladder carcinoma cell lines was also inhibited by TNP-470. However, the
      doses inhibitory to bladder carcinoma cells were 100-fold higher than the doses
      that were effective in the inhibition of endothelial cell proliferation. In vivo,
      TNP-470 significantly inhibited the growth of advanced KK-47 (67%) and MGH-U1
      (68%) tumors in SCID mice. CONCLUSIONS: Our results indicate that antiangiogenic
      therapy with TNP-470 is equally effective in advanced superficial and invasive
      bladder carcinoma models in mice. When our results are taken together with the
      reports of other laboratories, TNP-470 appears to be a promising candidate as a
      tumor suppressor in superficial and invasive bladder cancer.

PMID- 10962339
TI  - Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in
      the rat corpus cavernosum and dorsal nerve.
AB  - OBJECTIVES: To elucidate the effect of testosterone on penile nerve supply.
      METHODS: Three groups of 10 rats each were assessed; two groups were castrated
      and the third underwent a sham operation (control). After castration, one group
      received subcutaneous injection of testosterone while the others received sesame
      oil. At 8 weeks, the rats underwent a functional analysis. The evaluation
      included a subcutaneous injection with apomorphine to study centrally mediated
      erection, and cavernous nerve electrostimulation and papaverine injection to
      study peripherally mediated erection. At death, a penile midshaft specimen was
      taken for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase
      staining. RESULTS: In the apomorphine study, castrated rats had no erections, but
      the erectile function of those receiving testosterone was restored to the level
      of the controls. The mean numbers of NADPH-diaphorase-stained nerve fibers in the
      copora cavernosa and both dorsal nerves of castrated rats, at 165.8 +/- 20.0 and
      271.3 +/- 21.1, respectively, were significantly lower than those of the
      controls, at 271.7 +/- 14.6 and 471.2 +/- 27.6, respectively. Those of the
      testosterone replacement group, at 290.7 +/- 10.1 and 500.7 +/- 23.9,
      respectively, recovered to the control level. The intracavernosal pressure
      decreased significantly in the absence of testosterone, both after
      electrostimulation and intracavernosal papaverine injection, and recovered to the
      control level after testosterone replacement. CONCLUSIONS: Our results indicate
      that testosterone acts on the nervous system to mediate erection. When it is
      absent, there may be downregulation of both the production and activity of nitric
      oxide (NO), thereby decreasing the response to peripheral stimulation via the NO
      pathway. Testosterone replacement may upregulate NO activity to the control
      level.

PMID- 10962340
TI  - Effects of sildenafil on human penile blood vessels.
AB  - OBJECTIVES: To investigate the effects of sildenafil on human penile blood
      vessels and evaluate the interaction of sildenafil with neurogenic-mediated
      responses. Sildenafil is currently used in the treatment of erectile dysfunction.
      METHODS: Penile dorsal arteries and deep dorsal veins were obtained from 14
      multiorgan donors. Vascular rings were suspended in organ bath chambers, and the
      isometric tension was recorded. We then studied the effects of sildenafil on
      precontracted vessels and the neurogenic (noradrenergic and nitrergic) responses.
      RESULTS: Sildenafil (10(-9) to 3 x 10(-6) M) caused concentration-dependent
      relaxation and amplified the relaxation induced by sodium nitroprusside.
      Relaxation was unaffected by the inhibitor of nitric oxide synthase N(G)
      monomethyl-L-arginine (10(-4) M). Compared with zaprinast, sildenafil was 8 to 10
      times more potent in terms of the median effective concentration (EC(50)) values.
      Electrical field stimulation of the vessels under resting tension caused
      frequency-dependent contractions that were attenuated in the presence of
      sildenafil. When penile vessels were contracted after blockade of norepinephrine
      release with guanethidine (10(-6) M), electrical stimulation induced frequency
      dependent, nitric oxide-dependent relaxations that were enhanced by sildenafil.
      CONCLUSIONS: These results indicate that the relaxation of human penile arteries
      and veins induced by sildenafil involves inhibition of noradrenergic contraction,
      enhancement of neurogenic nitric oxide-mediated relaxation, and inhibition of
      smooth muscle contraction.

PMID- 10962342
TI  - Muscle-bone interactions, revisited.

PMID- 10962341
TI  - Tumor-induced osteomalacia and the regulation of phosphate homeostasis.
AB  - Tumor-induced osteomalacia (TIO) is a rare and unique syndrome characterized by
      hypophosphatemia, excessive urinary phosphate excretion, reduced 1,25
      dihydroxyvitamin D concentrations, and osteomalacia. Removal of the tumor is
      associated with a cure of the lesion. Several laboratories have now shown that
      conditioned medium derived from cultures of such tumors contain a small, heat
      sensitive substance ("phosphatonin") of <25,000 daltons that specifically
      inhibits sodium-dependent phosphate transport in cultured renal proximal tubular
      epithelia. This substance does not increase cyclic adenosine monophosphate (cAMP)
      formation in tubular epithelial cells and does not increase cAMP excretion in
      urine. A substance with similar properties is present in the circulation of
      patients on hemodialysis. A syndrome with a remarkably similar biochemical
      phenotype, namely, X-linked hypophosphatemic rickets (XLH), also has a
      circulating factor with properties similar, if not identical, to those of the
      tumor-derived factor, "phosphatonin." The molecular defect in XLH has been shown
      to be due to a mutant endopeptidase, PHEX, whose substrate might be
      "phosphatonin." Hypophosphatemia and other biochemical abnormalities in TIO are
      due to excessive production of "phosphatonin" with normal PHEX function, whereas
      the biochemical abnormalities in XLH are caused by a mutant PHEX enzyme that
      fails to process "phosphatonin."

PMID- 10962343
TI  - The importance of mineral in bone and mineral research.

PMID- 10962344
TI  - Femoral morphology and cross-sectional geometry of adult myostatin-deficient
      mice.
AB  - GDF-8, also known as myostatin, is a member of the transforming growth factor
      beta (TGF-beta) superfamily of secreted growth and differentiation factors that
      is expressed in vertebrate skeletal muscle. Myostatin functions as a negative
      regulator of skeletal muscle growth and myostatin null mice show a doubling of
      muscle mass compared with normal mice. We examined femoral morphology of adult
      myostatin-deficient mice to assess the effects of muscle fiber hypertrophy and
      hyperplasia on bone shape and cross-sectional geometry. Femora of age- and weight
      matched adult mice homozygous for the disrupted myostatin sequence were compared
      with those of wild-type controls (n = 8 per group). Results show that, as was the
      case in previous studies, myostatin null mice have hindlimb muscle masses that
      are approximately double those of controls. Myostatin-deficient mice exhibit
      third trochanters that are significantly larger than those of controls, whereas
      the femoral midshafts of the control and experimental mice do not differ
      significantly from one another in cortical area, bending moment of inertia, and
      polar moment of inertia. Our findings indicate that the increased muscle mass of
      myostatin-deficient mice primarily affects sites of muscle insertion, but does
      not induce additional cortical bone deposition in the diaphysis relative to
      controls. We therefore conclude that the expanded third trochanters of myostatin
      deficient subjects result from tendon and Sharpey fiber expansion associated with
      muscle growth rather than cortical bone deposition in response to increased
      levels of mechanical stress.

PMID- 10962345
TI  - Exercise-induced bone gain is due to enlargement in bone size without a change in
      volumetric bone density: a peripheral quantitative computed tomography study of
      the upper arms of male tennis players.
AB  - Bilateral bone characteristics of the humerus (proximal, shaft, and distal sites)
      and radius (shaft and distal sites) in 12 former Finnish national-level male
      tennis players (mean age 30 years) and their 12 age-, height-, and weight-matched
      controls were measured with peripheral quantitative computed tomography (pQCT).
      The pQCT variables analyzed were bone mineral content (BMC), total cross
      sectional area of bone (Tot.Ar), cross-sectional area of the marrow cavity
      (M.Cav.Ar), cortical bone (Co.Ar) and trabecular bone (Tr.Ar), volumetric density
      of cortical (Co.Dn) and trabecular (Tr. Dn) bone, cortical wall thickness
      (Co.Wi.Th), bone strength index (BSI), and principal moments of inertia (I(min)
      and I(max)). In the players, significant side-to-side differences, in favor of
      the dominant (playing) arm, were found in BMC (ranging 14%-27%), Tot.Ar (16%
      21%), Co.Ar (12%-32%), BSI (23%-37%), I(min) (33%-61%), and I(max) (27%-67%) at
      all measured bone sites, and in Co.Wi.Th. (5%-25%) at the humeral and radial
      shafts, and distal humerus. The side-to-side M.Cav.Ar difference was significant
      at the proximal humerus (19%) and radial shaft (29%). Concerning the players'
      Co.Dn and Tr.Dn, the only significant side-to-side difference was found in the
      Co.Dn of the distal humerus, with the playing arm showing a slightly smaller
      Co.Dn than the nonplaying arm (-2%). In controls, significant dominant-to
      nondominant side differences were also found, but with the majority of the
      differences being rather small, and significantly lower than those of the
      players. In conclusion, despite the large side-to-side differences in BMC, the
      volumetric bone density (Co.Dn, Tr.Dn) was almost identical in the dominant and
      nondominant arms of the players and controls. Thus, the players' high playing-arm
      BMC was due to increases in the Tot.Ar, M.Cav.Ar, Co.Ar, and CW.Th. In other
      words, the playing arm's extra bone mineral, and thus increased bone strength,
      was mainly due to increased bone size and not due to a change in volumetric bone
      density. These upper arm results may not be generalized to the entire skeleton,
      but the finding may give new insight into conventional dual-energy X-ray
      absorptiometry (DXA)-based bone density measurements when interpreting the
      effects of exercise on bone.

PMID- 10962346
TI  - Inorganic phosphate induces apoptosis of osteoblast-like cells in culture.
AB  - The major goal of this investigation was to test the hypothesis that one of the
      major products of bone resorption, inorganic phosphate (Pi), activates osteoblast
      apoptosis. Osteoblast-like cells were isolated from explants of human bone. In
      monolayer culture, these cells showed an osteogenic phenotype. Thus, the cells
      exhibited raised alkaline phosphatase activity, expressed osteogenic messenger
      RNA transcripts, and formed biological mineral. When these cells were treated
      with 1-7 mmol/L Pi there was a dose- and time-dependent decrease in cell
      viability. Accordingly, after 48 h, 5 mmol/L Pi reduced the number of viable
      osteoblast-like cells by 25%; 7 mmol/L Pi reduced the number of cells by 60%. By
      96 h, following treatment with 5 mmol/L Pi, the percentage of viable cells was
      30%, whereas 7 mmol/L Pi caused an almost complete loss of osteoblast viability.
      Osteoblast death was blocked by treating the cells with phosphonoformic acid, an
      inhibitor of the plasma-membrane Na-Pi transporter. Using morphological and end
      labeling procedures, we confirmed that cell death was through apoptosis. To probe
      the mechanism of cell death, osteoblast-like cells were probed with rhodamine
      123, a dye that is responsive to the membrane potential. We noted that Pi-treated
      cells displayed a profound loss of mitochondrial membrane potential, suggesting
      that the anion activated the death program through the induction of a
      mitochondrial membrane permeability transition. We conclude that high levels of
      osteoblast apoptosis observed at sites of bone resorption may be linked to
      release of Pi from bone mineral.

PMID- 10962347
TI  - Reduced G-protein-coupled-receptor kinase 2 activity results in impairment of
      osteoblast function.
AB  - Rapid phosphorylation of many G-protein-coupled receptors (GPCRs) by G-protein
      coupled receptor kinases (GRKs) accompanies stimulus-driven desensitization.
      Recent evidence suggests that GRKs and their associated arresting proteins, beta
      arrestins, function as essential elements in the GPCR-mediated mitogen-activated
      protein (MAP) kinase signaling cascade. We investigated the interaction between
      GRKs and MAP kinase activation by growth factors in UMR 106-H5 osteoblastic cells
      stably expressing a dominant negative mutant of GRK2 (K220R). Expression of K220R
      in osteoblastic cells results in reduced cellular proliferation, both basally and
      in response to insulin-like growth factor-1 (IGF-1), and blunting of IGF-1- and
      EGF-induced MAP kinase activation. Reduced MAP kinase activation is not
      associated with alterations in IGF-1-receptor autophosphorylation. Both a
      constitutively active Ras mutant and PMA fully activate MAP kinase in K220R
      cells. We found that disruption of the GRK2 gene results in: (1) reduced
      osteoblast proliferation in response to growth factors, and (2) impaired receptor
      tyrosine kinase activation of mitogenic signaling pathways. Thus, GRK2 may
      regulate growth factor responsiveness in osteoblasts by modulating multiprotein
      complex formation following receptor tyrosine kinase activation.

PMID- 10962348
TI  - Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase
      activity in human bone.
AB  - Glucocorticoids have an essential role in skeletal development and function but
      are detrimental in excess. In several tissues, glucocorticoid action is dependent
      upon the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes,
      which interconvert active cortisol (F) and inactive cortisone (E). We previously
      demonstrated the expression of 11beta-HSD isozymes in human osteosarcoma cell
      lines, osteoblast cultures, and fetal bone. We now characterize 11beta-HSD
      expression in adult human bone using specific antihuman 11beta-HSD antibodies,
      riboprobes, and enzyme activity studies. In addition, the effect of 11beta-HSD on
      bone metabolism in vivo was assessed using the 11beta-HSD inhibitor carbenoxolone
      in eight normal male volunteers. In fresh normal human bone tissue, both 11beta
      dehydrogenase (cortisol-to-cortisone conversion) and reductase (cortisone-to
      cortisol conversion) activities were demonstrated. There was considerable
      interindividual variation in the dehydrogenase, but not reductase, activity. In
      bone homogenates, activity was NADP-dependent with a K(m) for F of 4.8 +/- 1.2
      micromol/L, suggesting the presence of 11beta-HSD1. This was confirmed by reverse
      transcription-polymerase chain reaction (RT-PCR) analysis. Immunohistochemistry
      and in situ hybridization studies demonstrated 11beta-HSD1 isozyme expression in
      cells of the osteoblast lineage and in osteoclasts. The 11beta-HSD2 isozyme was
      expressed, but only in osteoblasts and at a low level. Ingestion of 300 mg of
      carbenoxolone by eight normal volunteers for 7 days resulted in a significant
      decrease in the bone resorption markers, pyridinoline (Pyr) and deoxypyridinoline
      (DPyr) (change in urinary Pyr/creatinine -1.55 +/- 0.55 [mean +/- SE], for
      DPyr/creatinine -0. 4 +/- 0.14 nmol/mmol; p < 0.05 for both), with no overall
      change in the bone formation markers C- and N-terminal propeptides of type I
      collagen (PICP and PINP). These data suggest that local tissue metabolism of
      glucocorticoids is likely to be important in determining the sensitivity of both
      osteoblasts and osteoclasts to glucocorticoids. In particular, variation in
      11beta-HSD isozyme expression and activity may explain individual variation in
      susceptibility to glucocorticoid-induced osteoporosis.

PMID- 10962349
TI  - Characterization of vitamin D receptor immunoreactivity in human bone cells.
AB  - The present study examined the expression of the vitamin D receptor (VDR) in
      adult human bone by immunohistochemical analysis. Antiserum from goats immunized
      with an N-terminal rat VDR peptide was purified by affinity chromatography. The
      purified antiserum recognized both endogenous rat and recombinant human VDR in
      Western blots. The purified antiserum was also able to specifically supershift
      the recombinant human VDR when analyzed in mobility shift assays.
      Immunohistochemical analysis of MG-63 cells, a human osteoblastic cell line known
      to express the VDR, revealed prominent staining over the nuclei of these cells.
      Immunostaining was greatly attenuated in the presence of an excess of the
      immunizing peptide. Analysis of bone biopsy samples from 16 normal human subjects
      immunostained for VDR protein showed strong, immunopositive staining over bone
      cells, particularly osteoblasts, in keeping with prior studies. In addition,
      there was significant immunoreactivity observed in nuclei of osteoclasts, lining
      cells and scattered bone marrow stromal cells of the adult human bone. Results
      showed that 298 osteoblasts out of 808 (36.9%) examined were immunopositive. It
      was also observed that 29 osteoclasts out of 125 (23%) contained VDR
      immunoreactivity. The ability to detect VDR in osteoclasts and stromal cell
      populations suggests that in addition to regulating osteoblast function, these
      other cell types are also direct targets of the hormone's action. These results
      demonstrate the utility of this purified antiserum in detecting the VDR in a
      variety of molecular techniques and should prove useful in examining receptor
      expression in various pathological conditions.

PMID- 10962350
TI  - Higher osteoclastic demineralization and highly mineralized cement lines with
      osteocalcin deposition in a mandibular cortical bone of autosomal dominant
      osteopetrosis type II: ultrastructural and undecalcified histological
      investigations.
AB  - In this study we report on histological and ultrastructural investigations of the
      mandibular cortical bone in a case of autosomal dominant osteopetrosis type II
      complicated by mandibular osteomyelitis. Histologically, there was a marked
      increase in the number and size of osteoclasts on the inner bone surface. An
      undecalcified preparation showed a pair of deeply stained (highly demineralized)
      and stain-phobic (highly mineralized) layers on the bone surface just beneath the
      osteoclasts. The layers were incorporated into the bone matrix during the
      remodeling process as thickened cement lines. A contact microradiogram of the
      cortical bone revealed highly mineralized layers at the cement lines, which were
      closely correlated with immunohistochemical evidence of deposition of osteocalcin
      at the thickened cement lines. Ultrastructural examination showed that the
      osteoclasts had a typical clear zone, but they were deficient in ruffled border
      formation and had numerous lysosomal vacuoles containing dense substances. An
      electron-dense amorphous material layer was present on the bone surface just
      beneath the osteoclasts as well as at the cement lines. The layer was partly
      composed of a short fibrillar material, and it partially revealed the lamellar
      structure. Consequently, an osteoclastic malfunction might be primarily involved
      in the process of bone matrix resorption rather than demineralization, resulting
      in higher demineralization and abnormal material deposition on the bone surface
      and at the cement lines. Furthermore, evidence of active osteoclastic bone
      resorption with a brush border formation at the bone involved in the inflammatory
      lesion in this case suggests that the osteoclastic malfunction is influenced and
      recovered by a microenvironment such as inflammatory cytokines.

PMID- 10962351
TI  - Megakaryocyte population in human bone marrow increases with estrogen treatment:
      a role in bone remodeling?
AB  - Skeletal effects of conventional hormone replacement therapy (HRT) are
      predominately antiresorptive, while high doses of estrogen have anabolic effects.
      The mechanisms mediating these effects are unclear but may involve cells in the
      bone marrow. We have investigated the in vivo effects of estrogen on the
      megakaryocyte (MK) population in bone marrow in 10 postmenopausal women before
      and after 2 years of conventional HRT, in 11 women after long-term, high-dose
      estradiol therapy, and in 2 premenopausal and 4 postmenopausal women who had
      received no previous estrogen treatment. Transiliac crest biopsies were halved
      and either decalcified and paraffin wax embedded for immunolocalization studies
      or dehydrated and embedded in LR White resin for histology. MKs were identified
      morphologically, and the bone marrow cell population and MK number quantified by
      cell counting in a defined area of view (1 mm(2)) from 5 randomly selected fields
      of bone marrow. Compared with pretreatment values, significantly higher MK
      numbers were found after conventional HRT treatment (before treatment, mean +/-
      SEM; 7.3 +/- 1.1 vs. after treatment, 18.0 +/- 1.6/5 mm(2); p < 0.0001), while
      the greatest MK number was associated with long-term, high-dose estradiol
      treatment (32.8 +/- 2.1/5 mm(2); p < 0.0001). Total bone marrow cell number did
      not differ significantly between groups. Immunolocalization studies revealed more
      intense estrogen receptor (ER)beta expression in MKs in the high-dose estradiol
      treated group but similar levels of weak ERalpha staining in MKs in the control
      and high-dose estrogen-treated groups. Positive immunoreactivity for transforming
      growth factor (TGF)beta1, 2, and 3 and TGFbeta receptor I, II, and III was
      detected in MKs, with more intense staining being demonstrated in the high-dose
      estradiol-treated group, particularly for TGFbeta2 and TGFbetaRI and II. Our
      results demonstrate an increase in the MK population in bone marrow from women
      treated with estrogen. The ability of MKs to express ERs and synthesise TGFbeta,
      a potent mitogen in osteoblast differentiation, suggests that these cells may
      play a role in mediating estrogen-induced effects on bone.

PMID- 10962352
TI  - Milk basic protein: a novel protective function of milk against osteoporosis.
AB  - Milk is recommended as an excellent calcium source for bone health. Moreover,
      milk is considered to contain other components effective for bone health. In our
      previous studies, using an unfractionated bone cell culture system, we found that
      milk whey protein, especially its basic fraction (milk basic protein [MBP]),
      suppressed bone resorption. In this present study, we investigated whether MBP
      could prevent bone loss in aged ovariectomized rats. Twenty-one 51-week-old
      female Sprague-Dawley rats were ovariectomized (ovx), and another seven rats
      received a sham operation (sham). After a 4-week recovery period, the ovx rats
      were separated into three groups, and they were then fed a control diet, a 0.01%
      MBP diet (0. 01% casein of the control diet replaced with MBP), or a 0.1% MBP
      diet for 17 weeks. The sham rats were fed the control diet. Bone mineral density
      (BMD) of the femur was measured by dual-energy X-ray absorptiometry in vivo. The
      BMD in the ovx-control group noticeably decreased during the experimental period
      in comparison with that in the sham group. However, the BMD in the OVX-0.1% MBP
      group was significantly higher than that in ovx-control group at weeks 12 and 16
      (p < 0.05). After the 17-week feeding period, the breaking energy of the excised
      femur of all groups was determined by use of a three-point bending rheolometer.
      The breaking energy in the ovx-control group was significantly lower than that in
      the sham group (p < 0.05). However, the breaking energy in the ovx-0.1% MBP group
      was significantly higher than that of the ovx-control group (p < 0.05). Urinary
      deoxypyridinoline (D-Pyr) level of the ovx-control group was higher than that of
      the sham group, whereas the level of D-Pyr excretion in the ovx-0.01% MBP and ovx
      0.1% MBP groups was significantly lower than that of the ovx-control group (p <
      0.05). These results suggest that MBP suppresses the osteoclast-mediated bone
      resorption and prevents bone loss caused by ovariectomy. Moreover, we performed
      an in vitro study using isolated osteoclasts from rabbit bone to investigate the
      possible mechanism. MBP dose-dependently suppressed the number of pits formed by
      these osteoclasts. This result indicates that MBP suppresses bone resorption by
      its direct effects on osteoclasts. To our knowledge, this study provides the
      first evidence that MBP directly suppresses osteoclast-mediated bone resorption,
      resulting in the prevention of the bone loss that occurs in ovx rats.

PMID- 10962353
TI  - Osteoclast differentiation from circulating mononuclear precursors in Paget's
      disease is hypersensitive to 1,25-dihydroxyvitamin D(3) and RANKL.
AB  - A characteristic feature of Paget's disease is an increase in the number of
      osteoclasts in bone. Osteoclasts are formed from mononuclear phagocyte precursors
      that circulate in the monocyte fraction of peripheral blood. These cells require
      the presence of RANK ligand (RANKL)-expressing osteoblastic cells and human
      macrophage colony-stimulating factor (M-CSF) to form osteoclasts in vitro. To
      determine the role of osteoclast differentiation from circulating precursors in
      Paget's disease, we cultured monocytes from Paget's patients and gender- and age
      matched normal controls with no evidence of bone disease for up to 21 days in the
      presence of UMR 106 cells and various concentrations of M-CSF (1-25 ng/mL) and
      1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] (10(-10) to 10(-7) mol/L). Relative
      to controls, there was a significant increase in the extent of osteoclast
      differentiation from pagetic monocytes as assessed by expression of tartrate
      resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and lacunar bone
      resorption. Serial dilution experiments (2 x 10(5) to 2 x 10(2) cells/well)
      showed no difference in the concentration of osteoclast precursors in the
      peripheral blood. In Paget's patients with high serum alkaline phosphatase (sAP)
      levels, increased sensitivity to the osteoclastogenic effect of 1,25(OH)(2)D(3)
      was noted. Osteoclast differentiation did not occur when M-CSF was substituted by
      interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R), and these factors did
      not stimulate osteoclast differentiation in the presence of M-CSF. In this in
      vitro coculture system, osteoclast formation was inhibited by osteoprotegerin in
      a dose-dependent manner. In the presence of RANKL (5-30 ng/mL) and M-CSF (25
      ng/mL), osteoclast formation and bone resorption were significantly increased in
      cultures of monocytes from patients with high and low sAP levels as compared with
      normal controls. Our findings suggest that the increase in osteoclast numbers
      seen in Paget's disease results not from an increase in the number of circulating
      precursors in peripheral blood but rather from an increased sensitivity of
      osteoclast precursors to the humoral factors, 1,25(OH)(2)D(3) and RANKL, which
      regulate osteoclast formation.

PMID- 10962354
TI  - Absence of measles virus and canine distemper virus transcripts in long-term bone
      marrow cultures from patients with Paget's disease of bone.
AB  - The presence of intranuclear inclusions in pagetic osteoclasts with similar
      characteristics to those seen in some slow viral diseases has lead to the
      hypothesis that Paget's disease is caused by a similar infection. Bone marrow
      aspirates from seven patients with hemipelvic Paget's disease were taken from
      both sides of the pelvis and cultured under identical conditions. RNA was
      extracted after approximately 2 weeks of culture and reverse transcriptase-linked
      polymerase chain reaction used to investigate the expression of measles and
      canine distemper virus RNA. We were unable to detect the presence of measles
      virus (MV) or canine distemper virus (CDV) transcripts in bone marrow cultures
      from either affected or unaffected sites in any of our patients. The results of
      this study do not support a role for MV or CDV in the pathogenesis of Paget's
      disease of bone.

PMID- 10962355
TI  - Long-term trends in the incidence of Paget's disease of bone.
AB  - Existing data on the epidemiology of Paget's disease of bone are limited by the
      lack of directly determined secular trends in clinically diagnosed Paget's
      disease. In the current study, we examine trends in Paget's disease incidence in
      Olmsted County, MN, using data from the Rochester Epidemiology Project medical
      records linkage system. During the period 1950 through 1994, 236 Olmsted County,
      MN residents were diagnosed for the first time with Paget's disease of bone at a
      mean age of 69.6 years. Overall, there were 129 (54.7%) men and 107 women, and
      the age-adjusted incidence of Paget's disease was 12.7 per 100,000 person-years
      (95% CI 10.4-14.9) among the men compared with 7.0 per 100,000 person-years (95%
      CI 5.6-8.3) among Olmsted County women (male/female ratio of 1.8:1). The higher
      incidence in males compared with females and the increase in incidence with older
      age were statistically significant. The incidence of Paget's disease in Olmsted
      County seems to have increased over the first part of the study period and then
      declined. This may have resulted from ascertainment bias: the introduction of a
      12-test automated serum chemistry panel in 1974 might have led to a sudden
      increase in the apparent incidence of Paget's disease followed by a compensatory
      decrease. In addition, there was a decrease in the proportion of patients who
      were symptomatic at diagnosis, from 36% in 1950-1959 to 27% in 1980-1994. This
      finding also suggests that routine measurement of alkaline phosphatase may have
      led to more diagnosis of asymptomatic individuals. The subsequent fall in the
      incidence of Paget's disease is consistent with previous reports, although this
      apparent decline could be artifactual to the extent that the reservoir of
      undiagnosed cases in the population was exhausted by earlier testing.

PMID- 10962356
TI  - Smoking and bone metabolism in elderly women.
AB  - Cigarette smoking has been implicated as a risk factor for osteoporosis. In the
      present study, the relationship between smoking and bone mineral density,
      calcitropic hormones, calcium absorption, and biochemical indices related to bone
      and mineral metabolism was examined at baseline, in subjects recruited for an
      osteoporotic study. The subjects included 489 elderly women, aged 65-77 years.
      After exclusions (thiazide users), 54 women constituted the smoking group and 390
      women were classified as nonsmokers. The effect of frequency of smoking was also
      examined in this population (33 light smokers [<1 pack/day] and 21 heavy smokers
      [>1 pack/day]). Adjusted mean total body bone mineral density was 4% lower (0.968
      +/- 0.019 vs. 1.009 +/- 0.004) and the total hip density was 6% lower (0.778 +/-
      0.024 vs. 0.826 +/- 0.006) in heavy smokers compared with nonsmokers. At the
      other sites measured (spine, midradius, femoral neck, trochanter, and Ward's
      triangle), a similar nonsignificant trend was observed. The adjusted mean calcium
      absorption corrected for weight was lower (13%) both in light and heavy smokers
      compared with nonsmokers, and serum 25-hydroxyvitamin D was significantly lower
      (16%) in heavy smokers than nonsmokers. Serum parathryroid hormone (PTH) was
      higher in heavy smokers, but was not significantly different from that of
      nonsmokers. A significant increase in bone remodeling markers, serum osteocalcin
      (4.35 +/- 0.271 vs. 3.79 +/- 0. 066) and urine N-telopeptide/creatinine (NTx/Cr)
      ratio (74.5 +/- 5. 75 vs. 49.8 +/- 1.4) was seen in heavy smokers compared with
      nonsmokers. These results suggest that smoking lowers bone mineral density, and
      is a result of decreased calcium absorption associated with secondary
      hyperparathyroidism and increased bone resorption.

PMID- 10962357
TI  - Stress fracture in military recruits: gender differences in muscle and bone
      susceptibility factors.
AB  - A total of 693 female U.S. Marine Corps recruits were studied with anthropometry
      and dual-energy X-ray absorptiometry (DXA) scans of the midthigh and distal third
      of the lower leg prior to a 12 week physical training program. In this group, 37
      incident stress fracture cases were radiologically confirmed. Female data were
      compared with male data from an earlier study of 626 Marine recruits extended
      with additional cases for a total of 38 stress fracture cases. Using DXA data,
      bone structural geometry and cortical dimensions were derived at scan locations
      and muscle cross-sectional area was computed at the midthigh. Measurements were
      compared within gender between pooled fracture cases and controls after excluding
      subjects diagnosed with shin splints. In both genders, fracture cases were less
      physically fit, and had smaller thigh muscles compared with controls. After
      correction for height and weight, section moduli (Z) and bone strength indices
      (Z/bone length) of the femur and tibia were significantly smaller in fracture
      cases of both genders, but patterns differed. Female cases had thinner cortices
      and lower areal bone mineral density (BMD), whereas male cases had externally
      narrower bones but similar cortical thicknesses and areal BMDs compared with
      controls. In both genders, differences in fitness, muscle, and bone parameters
      suggest poor skeletal adaptation in fracture cases due to inadequate physical
      conditioning prior to training. To determine whether bone and muscle strength
      parameters differed between genders, all data were pooled and adjusted for height
      and weight. In both the tibia and femur, men had significantly larger section
      moduli and bone strength indices than women, although women had higher tibia but
      lower femur areal BMDs. Female bones, on average, were narrower and had thinner
      cortices (not significant in the femur, p = 0.07). Unlike the bone geometry
      differences, thigh muscle cross-sectional areas were virtually identical to those
      of the men, suggesting that the muscles of the women were not relatively weaker.

PMID- 10962358
TI  - Effects of dietary calcium depletion and repletion on dynamic determinants of
      tibial bone volume in two inbred strains of mice.
AB  - As an adjunct to our efforts to identify the genes that determine peak bone
      density, we examined phenotypic differences between two inbred strains of mice,
      C3H/HeJ (C3H) and C57BL/6J (B6), which are of similar size but differ with
      respect to peak bone density (e.g., C3H mice have 53% higher femoral bone density
      than B6 mice). The current studies were intended to compare the skeletal
      responses of C3H and B6 mice to 2 weeks of dietary calcium (Ca) depletion,
      followed by 2 weeks of Ca repletion. Initial studies showed that: (a) femur dry
      weight decreased during Ca depletion in both C3H and B6 mice (by 25% and 19%,
      respectively, p < 0.001) and most of this loss was recovered during Ca repletion;
      and (b) serum alkaline phosphatase (ALP) activity increased during Ca depletion,
      in both strains of mice (p < 0.001), and returned to normal after Ca repletion.
      Histological analyses of ground cross sections prepared at the tibiofibular
      junction showed that Ca-depletion increased medullary area in both C3H and B6
      mice (indicating endosteal bone loss, p < 0.01), with reversal during Ca
      repletion. There were no effects of Ca depletion or repletion on periosteal bone
      growth. Endosteal bone forming surface and endosteal mineral apposition decreased
      during Ca depletion and increased during repletion in both C3H and B6 mice (p <
      0.05). Net bone formation decreased during Ca depletion in C3H mice, but not B6
      mice (p < 0.01), and was normal during Ca repletion in both strains. Endosteal
      bone resorbing surface and net bone resorption increased during Ca depletion and
      decreased during repletion in both strains (p < 0.01). A supplemental study (of
      Ca depletion without repletion) confirmed the effects of Ca depletion on femoral
      dry weight and serum ALP activity (p < 0.001 for each). This supplemental study
      also showed that Ca deficiency increased serum parathyroid hormone (PTH) (p <
      0.05) and decreased (tibial) cortical bone area and cortical mineral content (p <
      0.05 to p < 0.001) in both strains of mice. Together, these data demonstrate that
      the skeletal responses to Ca depletion and repletion are, qualitatively, similar
      in C3H and B6 mice.

PMID- 10962359
TI  - Temporal and spatial expression of bone morphogenetic protein-2, -4, and -7
      during distraction osteogenesis in rabbits.
AB  - The Ilizarov method of limb lengthening makes use of the fact that osteogenesis
      is induced at an osteotomy site when distraction is applied. It is unknown at
      present how the mechanical forces created by distraction are translated into
      biological signals. Because bone morphogenetic proteins (BMPs) are potent
      inducers of osteogenesis in many experimental systems, they are obvious
      candidates for playing a role in this process. In this study, we investigated the
      temporal and spatial expression of BMP-2, -4, and -7 proteins during distraction
      osteogenesis using immunohistochemistry. An osteotomy was performed on the right
      tibiae of white New Zealand rabbits. After a delay of 7 days, distraction was
      started at a rate of 0.25 mm/12 h for 3 weeks, followed by a 3 week consolidation
      phase. Each week after osteotomy one rabbit was killed for immunohistochemical
      studies. Staining for BMP-2, -4, and -7 was evident before distraction was
      applied and was mainly localized to mesenchymal cells and osteoblastic cells in
      the periosteal region. After distraction was started, the typical fibrous
      interzone developed between the osteotomy fragments, where both intramembranous
      and endochondral ossification were noted. In this area, cells resembling
      fibroblasts and chondrocytes, but not mature osteoblasts, showed intense staining
      for all three BMPs. This high level of expression was maintained during the
      entire distraction phase and then gradually disappeared during the consolidation
      phase. These results are compatible with the hypothesis that BMPs play an
      important role in the signaling pathways that link the mechanical forces created
      by distraction to biological responses.

PMID- 10962360
TI  - [Toward an effective treatment of androgenetic alopecia?].

PMID- 10962361
TI  - [Physiopathology of scalp disorders].

PMID- 10962362
TI  - [Clinical aspects of androgenetic alopecia].

PMID- 10962363
TI  - [Techniques for evaluating the course of androgenetic alopecia].

PMID- 10962364
TI  - [Androgenetic alopecia: drug treatment].

PMID- 10962365
TI  - [Management of alopecia in the woman].

PMID- 10962366
TI  - [Drug-induced alopecia].

PMID- 10962367
TI  - [Diagnosis and treatment of baldness].

PMID- 10962368
TI  - [Hair loss associated with human immunodeficiency virus].

PMID- 10962369
TI  - [Acquired cicatricial alopecia in the adult].

PMID- 10962371
TI  - [ [In Process Citation]

PMID- 10962370
TI  - [Hair transplant].

PMID- 10962372
TI  - [The levels of quality of life].

PMID- 10962373
TI  - [Quality of life index in dermatology].

PMID- 10962374
TI  - [General and specific tools to measure quality of life in dermatology].

PMID- 10962375
TI  - [Acne and quality of life].

PMID- 10962377
TI  - [Atopic dermatitis: assessment of quality of life].

PMID- 10962376
TI  - [Androgenetic alopecia and quality of life].

PMID- 10962378
TI  - [Psoriasis: assessment of quality of life].

PMID- 10962379
TI  - [Transcultural adaptation of levels of quality of life: a need and an emergency
      for dermatologists].

PMID- 10962380
TI  - [Inhibition of apoptosis: a new therapeutic approach to prevent liver ischemia
      reperfusion lesions?].

PMID- 10962381
TI  - [Should adenomas be treated surgically? Results of a symposium].

PMID- 10962382
TI  - [Multicenter study of intrafamilial transmission of hepatitis C virus in human
      immunodeficiency virus infection].
AB  - OBJECTIVE: Intrafamilial transmission of hepatitis C virus in human
      immunodeficiency virus and hepatitis C virus co-infections is not well
      documented. This cross-sectional study evaluated the transmission of hepatitis C
      virus in the sexual partners of hepatitis C virus and human immunodeficiency
      virus co-infected patients. METHODS: Hemophiliacs and transfused hepatitis C
      virus and human immunodeficiency virus co-infected patients who were being seen
      in three French university hospitals, and their sexual partners were studied by a
      face-to-face interview using an epidemiological questionnaire and by biological
      tests: antibodies against hepatitis C virus, hepatitis C virus RNA, and ALT
      activity. RESULT: Fifty-two subjects were included: 26 cases and their 26 sexual
      partners. Three sexual partners (11.5 %) had anti-hepatitis C virus antibodies,
      two of whom had an undetermined RIBA test. All three had a risk factor for
      hepatitis C virus infection (transfusion, intra-muscular injections with re
      usable needles). Two of these three partners were also human immunodeficiency
      virus antibody positive. Hepatitis C virus RNA was negative in all sexual
      partners. CONCLUSION: This study provides evidence of a low prevalence of anti
      hepatitis C virus antibodies in sexual partners of hepatitis C virus and human
      immunodeficiency virus co-infected patients. It does not support intra-familial
      transmission of hepatitis C virus.

PMID- 10962383
TI  - [Comparison of laparoscopic ultrasound and cholangiography during laparoscopic
      cholecystectomies. Results of a prospective study].
AB  - AIM: Prospective evaluation of the results of laparoscopic ultrasound and
      cholangiography to investigate choledocholithiasis and detect variations in
      biliary anatomy during laparoscopic cholecystectomies. METHODS: The biliary trees
      of 600 patients who underwent laparoscopic cholecystectomy were routinely
      explored by laparoscopic ultrasound and cholangiography. RESULTS: Laparoscopic
      ultrasound was performed in all 600 cases. Cholangiography was performed in 498
      (83%). Laparoscopic ultrasound required less time than cholangiography: 10.2
      minutes versus 17.9 minutes (P=0.0001). Common bile duct stones were detected
      intraoperatively in 40 cases (7%). Both methods were equally effective. The
      sensitivity of laparoscopic ultrasound was 80% and its specificity 99%. For
      cholangiography these values were 75% and 98% respectively. For laparoscopic
      ultrasound, false positives and false negatives were noted in the first 45 cases
      of individual trainees. Nevertheless, cholangiography showed 30 anatomical
      anomalies and laparoscopic ultrasound only 15. CONCLUSION: Laparoscopic
      ultrasound can be performed rapidly and in all cases. Results are comparable to
      cholangiography in the detection of common duct stones. Individual training is
      necessary to optimize efficacy. Anatomical anomalies are often missed.

PMID- 10962385
TI  - [Methodological aspects of screening evaluation: apropos of screening for
      hepatitis C].

PMID- 10962384
TI  - Non invasive prediction of severe fibrosis in patients with alcoholic liver
      disease.
AB  - OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of
      noninvasive markers of liver fibrosis in alcoholic liver disease. PATIENTS AND
      METHODS: Fifty-four clinical and biochemical parameters including serum fibrosis
      markers (hyaluronate and transforming growth factor beta1) were analyzed in 146
      consecutive heavy drinkers (106 men, 40 women; mean age 49.2 years). Following
      liver biopsy, fibrosis was evaluated using a semi-quantitative scoring system (no
      fibrosis (0) to severe fibrosis (3 + )). Multivariate analysis was performed to
      determine the markers that were best correlated with the fibrosis score. RESULTS:
      Fifty-nine patients (40.4 %) had severe fibrosis (3 +) while 87 (59.6 %) had no
      fibrosis or moderate fibrosis (0 to 2 +). In multivariate analysis, serum
      hyaluronate and the prothrombin index were the best markers for the prediction of
      severe fibrosis. Hyaluronate and the prothrombin index had a diagnostic accuracy
      of 91.1 % and 89.7 %, respectively in the whole population. Finally, a
      significant negative correlation was found between hyaluronate and the
      prothrombin index (r =- 0.86, P <0.0001). CONCLUSIONS: Using only hyaluronate and
      the prothrombin index, 9 out of 10 alcoholic patients can be correctly classified
      according to the severity of liver fibrosis.

PMID- 10962386
TI  - [Screening for colorectal cancer in persons with occupational exposure to
      asbestos].

PMID- 10962387
TI  - [Acid suppression therapy is not required after one-week anti-Helicobacter pylori
      triple therapy for duodenal ulcer healing].
AB  - AIM: To compare healing of Helicobacter pylori-related non complicated duodenal
      ulcer after one-week eradication triple therapy alone and after triple therapy
      with further 3-weeks antisecretory treatment with ranitidine. METHODS: Three
      hundred and forty three patients with symptomatic H. pylori positive duodenal
      ulcer were included in this randomized double-blind placebo controlled study. H.
      pylori infection was established by rapid urease test and histopathology of
      antral biopsies. All patients were treated for one week with ranitidine 300 mg
      b.i.d., amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d., and then randomly
      treated for the following 3 weeks either with ranitidine 300 mg once daily
      (triple therapy + ranitidine, n =180) or placebo (triple therapy alone, n =163).
      Ulcer healing was assessed by endoscopy 4 weeks after inclusion. H. pylori
      eradication was established by (13) C-urea breath testing 5 weeks after the end
      of triple therapy. RESULTS: In intention to treat, duodenal ulcer healed at 4
      weeks in 86 % of patients treated with triple therapy + ranitidine and in 83 % of
      patients treated with triple therapy alone (equivalence: 90 % CI [-3. 8 %; 9.2
      %]). The H. pylori eradication rates were 67 % and 69 % respectively. Ulcer
      healed in 88 % of patients in whom H. pylori eradication was achieved and in 77 %
      of patients in whom eradication failed. CONCLUSION: These results demonstrate
      that one-week triple therapy alone is highly effective in healing non complicated
      H. pylori associated duodenal ulcer without additional antisecretory treatment.

PMID- 10962389
TI  - [Long-term prognosis of gastric cancer in the population of Cote-d'Or].
AB  - AIMS: The aim of this study was to determine long term prognostic factors of
      gastric cancer in a population-based series. METHODS: Out of 1 462 gastric
      cancers diagnosed in the Cote-d'Or area (494 000 residents) over a 20-year period
      (1976-1995), 649 (44.4 %) were resected for cure. Prognostic factors were
      determined using the actuarial method and relative survival and a
      multidimensional relative survival model. RESULTS: The 10-year crude survival
      rate was 8.7 % and the corresponding relative survival rate was 14.9 %. Age,
      stage and period of diagnosis were independent prognostic factors. After surgery
      for cure, operative mortality decreased from 18.3 % (1976-1979) to 6.6 % (1988
      1991) and 10-year relative survival increased from 30.8 % to 37.2 % (NS). After
      resection for cure (postoperative mortality excluded), the 10-year survival rate
      remained stable over time. Stage at diagnosis was the main prognostic factor: the
      relative risk of death was more than 10 times higher at stages IIIB and IV than
      at stage I. Age, site and macroscopic type of growth were prognostic factors
      independently of stage. Prognosis did not improve over time after resection for
      cure. CONCLUSION: Although improving, the overall prognosis of gastric cancer
      remains poor. Improvement in prognosis was mainly due to decrease in operative
      mortality. Earlier diagnosis and effective adjuvant treatment represent two ways
      to improve prognosis.

PMID- 10962388
TI  - [Effects of endocrine peptides on proliferation, migration and differentiation of
      human endothelial cells].
AB  - AIMS: We aimed to evaluate the effects of several peptides (substance P, VIP,
      neuropeptide Y, bombesin, glucagon and somatostatin) on the proliferation,
      migration and differentiation of human endothelial cells and their modulation by
      an anti-angiogenic factor, endostatin. METHODS: Human endothelial cells (HUVEC)
      were isolated from umbilical veins. Their proliferation was measured by the
      incorporation of tritiated thymidine. Their migration was evaluated by using an
      haptotactic assay performed in Boyden chambers, after metabolic labeling of HUVEC
      through (35) S-methionin. Differentiation was evaluated as the capacity for HUVEC
      to form capillaries. RESULTS: Endothelial cell proliferation was increased by
      neuropeptide Y, bombesin and glucagon. Somatostatin induced a significant
      decrease in basal and stimulated endothelial cell proliferation. The migration of
      HUVEC increased in the presence of substance P, VIP, neuropeptide Y, bombesin,
      glucagon and somatostatin. The number of capillaries was increased by substance P
      and VIP and decreased by neuropeptide Y, bombesin and somatostatin. Endostatin
      induced a significant decrease in endothelial cell proliferation in the basal
      state and after stimulation by neuropeptide Y and bombesin. Endostatin had no
      additive effect on the anti-proliferative action of somatostatin. CONCLUSIONS:
      Our results suggest a role for endocrine peptides in the regulation of tumor
      angiogenesis. The potent anti-angiogenic effect of somatostatin may promote new
      therapeutic strategies.

PMID- 10962390
TI  - [Bleeding peptic ulcer: natural history and place of endoscopic hemostasis].

PMID- 10962391
TI  - [Vascular pathology of the portal vein distal branches: a rare cause of liver
      transplantation and a protean clinical presentation].
AB  - We report 5 cases of liver transplantation which showed phlebosclerotic lesions
      of the distal portal vein on the explant confirming a diagnosis of hepatoportal
      sclerosis. This lesion was associated with nodular regenerative hyperplasia (2
      cases), incomplete septal cirrhosis (4 cases) and tumors (2 cases, 1 adenoma and
      1 hepatocellular carcinoma). Indications for transplant were chronic liver
      failure (1 case), encephalopathy without liver insufficiency (2 cases), an
      adenoma (1 case), a liver mass (1 case). Three patients out of 5 had a past
      history of surgical portacaval shunts to treat variceal bleeding non related to
      cirrhosis, one had a spontaneous portacaval shunt, and 2 had undergone a
      splenectomy for pancytopenia. The review of liver biopsies (4 cases out of 5)
      performed during surgery showed distal portal vein phlebosclerotic lesions. The
      diagnosis of hepatoportal sclerosis associated with complications, which is
      obvious retrospectively, is seldom made prior to transplantation. Portacaval
      shunts could play at least a partial role in the progressive deterioration of the
      liver.

PMID- 10962392
TI  - [Efficacity of treatment with lamivudine in two patients with severe reactivation
      of hepatitis B after withdrawal of chemotherapy].
AB  - Reactivation of chronic infection is a serious complication during and especially
      after the withdrawal of cancer chemotherapy in hepatitis B virus carriers.
      Mortality is high, ranging from 4 to 20%. We report two cases of severe
      reactivation, after withdrawal of chemotherapy for chronic lymphocytic leukemia
      in one case and for a bladder tumor in the other. Recovery occurred with
      lamivudine therapy. Morbidity and mortality are common in these cases, especially
      when intensive chemotherapy and/or chronic hepatitis and/or precore mutants
      viruses are involved. Although lamivudine seems to be effective in these cases,
      prophylactic use has not been clearly defined and must be evaluated.

PMID- 10962393
TI  - [Gastric stromal tumor with osteoclast-like multinucleated giant cells during
      Lynch II syndrome].
AB  - We report an unusual case of gastric tumor: a stromal tumor with osteoclast-like
      giant cells. This type of cells has been described in epithelial tumors,
      especially in adenocarcinoma of the pancreas, lung, thyroid and breast. It has
      also been reported in smooth cell tumors such as uterine leiomyosarcoma and
      malignant fibrous histiocytoma. In our patient, this gastric stromal tumor with
      osteoclast-like giant cells was diagnosed in a man with adenocarcinoma of the
      colon in the context of a familial cancer syndrome. This is the first report of
      stromal tumor with osteoclast-like giant cells associated with Lynch syndrome.

PMID- 10962395
TI  - Rising hospital admissions and mortality from hepatocellular carcinoma in
      Portugal.

PMID- 10962394
TI  - [Probable cutaneous sarcoidosis associated with combined ribavirin and interferon
      alpha therapy for chronic hepatitis C].

PMID- 10962396
TI  - [Acute pancreatitis secondary to gastric duplication communicating with a common
      pancreatic duct].

PMID- 10962397
TI  - [Prospective study of the prevalence of protozoan gastroduodenal infection in a
      cohort of dyspepsia patients].

PMID- 10962398
TI  - [Secondary hyponatremia caused by omeprazole treatment].

PMID- 10962400
TI  - [Benign angiolipoma of the Bauhin valve causing severe digestive tract bleeding].

PMID- 10962399
TI  - [Lansoprazole-induced hyponatremia].

PMID- 10962401
TI  - [Eosinophilic gastroenteritis: an unusual cause of dysphagia].

PMID- 10962402
TI  - Lymphatic drainage of carbon particles injected into the pleural cavity of the
      monkey, as studied by video-assisted thoracoscopy and electron microscopy.
AB  - OBJECTIVES: The aim of this study was to clarify the dynamics of lymphatic
      drainage of the pleural cavity to understand the mechanism of malignant pleural
      effusion. METHODS: We injected carbon particles into the pleural cavity of
      monkeys subjected to general anesthesia. We then observed the parietal pleura
      with a video-assisted thoracoscope and scanning and transmission electron
      microscopes to examine the regions of the parietal pleura where the carbon
      particles had been absorbed. RESULTS: The video-assisted thoracoscope showed that
      the carbon particles had gone directly to the costal, mediastinal, and
      diaphragmatic pleura by 10 to 15 minutes after injection. From the scanning and
      transmission electron microscopes, we found that the parietal pleura in the
      costal and mediastinal regions consisted of 3 elements: a layer of small
      mesothelial cells, the macula cribriformis, and lymphatic lacunae. Stomata (3-5
      microm in diameter) were found between the small mesothelial cells. The macula
      cribriformis was composed of densely packed collagen fibrils and had many
      foramina (3-10 microm in diameter). Intrapleurally injected carbon particles were
      carried into the lymphatic lacunae via the stomata and vesicles of the
      mesothelial cells and the foramina of the macula cribriformis. The lymphatic
      lacunae filled with carbon particles were richly distributed in both the anterior
      costal pleura and the mediastinal pleura. CONCLUSION: We suggest that the
      mesothelial stomata and the macula cribriformis are structures essential to the
      absorption of macromolecules and cellular elements from the pleural cavity into
      the lymphatic system.

PMID- 10962403
TI  - The mitral homograft-is it worthwhile?

PMID- 10962404
TI  - Homograft mitral valve replacement: five years' results.
AB  - OBJECTIVE: Results of mitral valve replacement with a mitral homograft were
      evaluated at 5 years to assess the suitability of the procedure. METHODS: Thirty
      seven patients (25 male subjects) aged 10 to 49 years (mean, 32 +/- 10 years)
      with rheumatic mitral valve disease underwent total (n = 35) or partial (n = 2)
      mitral valve replacement with a fresh antibiotic-preserved (n = 23) or
      cryopreserved (n = 14) mitral homograft. The predominant lesion was mitral
      stenosis (n = 30). RESULTS: There were 5 early deaths. Operative survivors were
      followed up for 1 to 60 months (mean, 26.6 +/- 12 months). Among these, 21
      patients had severe mitral regurgitation during the follow-up period; 3 died and
      8 underwent reoperation. The homograft failure rate was not affected by
      preoperative physiologic lesion (stenosis vs regurgitation, P =.4), type of
      homograft (antibiotic-preserved vs cryopreserved homograft, P =.9), papillary
      muscle pretreatment (yes vs no, P =.9), or addition of posterior collar
      annuloplasty (yes vs no, P =.2). Among the remaining patients, 5 had moderate
      mitral regurgitation, 4 had either trivial or mild mitral regurgitation, and 2
      were lost to follow-up. Study of the explanted mitral homografts (n = 8) revealed
      that disruption of one of the donor papillary muscles was responsible for early
      failures (n = 2), whereas cuspal and chordal degeneration was responsible for
      late failures (n = 6). Microscopically, the explanted valve lacked any viable
      cellular elements, and there was no evidence of immunologic injury to the
      homografts. CONCLUSION: The mitral homograft did not fulfill our expectations as
      a suitable substitute for the diseased mitral valve.

PMID- 10962405
TI  - Effect of flow competition on internal thoracic artery graft: postoperative
      velocimetric and angiographic study.
AB  - OBJECTIVES: To assess the effects of competitive blood flow on internal thoracic
      artery grafts, we investigated postoperative flow velocity characteristics and
      angiographic findings of the grafts with various grades of native coronary artery
      stenosis. METHODS: Fifty patients who had an internal thoracic artery graft to
      the left anterior descending artery underwent intravascular Doppler graft
      velocimetry during postoperative angiography. Patients were divided into 3 groups
      according to the grade of native coronary stenosis: group H (28 patients), 80%
      stenosis or greater; group M (16 patients), 60% to 79% stenosis; and group L (6
      patients), 40% to 59% stenosis. Phasic flow velocity of the grafts was measured
      with an intravascular Doppler ultrasound-tipped guide wire during angiography.
      Graft flow volume was calculated from the diameter and the average peak velocity.
      RESULTS: Average peak velocity (group H, 27.1 +/- 8.6 cm/s; group M, 16.9 +/- 3.9
      cm/s; group L, 7.2 +/- 3.7 cm/s), distal graft diameter (group H, 2.27 +/- 0.23
      mm; group M, 2. 00 +/- 0.28 mm; group L, 1.07 +/- 0.27 mm), and calculated graft
      flow volume (group H, 33.1 +/- 12.0 mL/min; group M, 16.2 +/- 5.8 mL/min; group
      L, 2.3 +/- 2.0 mL/min) significantly differed among the 3 groups. Graft flow in
      diastole and systole also differed among the 3 groups. CONCLUSIONS: Competitive
      blood flow reduces internal thoracic artery graft flow and diameter according to
      the grade of the native coronary artery stenosis. These data suggest that
      grafting the internal thoracic artery to the coronary artery with stenosis of a
      low grade can cause graft atrophy and failure.

PMID- 10962406
TI  - Aortic arch branches are no longer a blind zone for transesophageal
      echocardiography: a new eye for aortic surgeons.
AB  - OBJECTIVES: Branch arteries of the aortic arch have been a blind zone for
      transesophageal echocardiography. Information regarding blood flow, which is
      important in both planned and emergency operations on the aorta, has therefore
      been limited. We have established a technique for visualizing these arteries in
      nearly all cases. METHODS: In 25 consecutive patients requiring either planned or
      emergency operations on the aorta, the branch arteries were visualized whenever
      cerebral malperfusion was suspected. Lateral flexion of the probe tip was used
      when the trachea interfered with visualization of the arteries. RESULTS: The left
      subclavian, left and right common carotid, right subclavian, innominate, and left
      and right vertebral arteries were visualized in 96% (24/25), 92% (23/25), 96%
      (24/25), 100% (25/25), 84% (21/25), 92% (22/24), and 88% (21/24), respectively.
      The origin of the innominate artery was visualized in 36% (9/25). In some cases,
      dissection extended into branch arteries during surgery or during conservative
      therapy. When the subclavian artery was clamped, retrograde flow was detected in
      the vertebral artery (steal flow). The cannula for selective cerebral perfusion
      occasionally was entered into the right common carotid or subclavian artery and
      obstructed the other branch with a balloon. CONCLUSIONS: The branch arteries of
      the aortic arch, including the vertebral artery, are no longer a blind zone for
      transesophageal echocardiography. The information obtained with our new
      transesophageal echocardiography technique is helpful for diagnosis, monitoring,
      and decision making during aortic surgery and in critical care medicine.
      Visualizing these vessels is worth the effort.

PMID- 10962407
TI  - Sutureless coronary artery bypass with biologic glued anastomoses: preliminary in
      vivo and in vitro results.
AB  - OBJECTIVE: As heart surgery becomes increasingly focused on minimally invasive
      techniques, it has become apparent that conventional techniques of anastomosis
      will need to be severely altered or abandoned. Toward that end, we developed and
      tested in vitro and in vivo coronary artery bypass graft anastomoses using a
      biologic glue formulated from bovine albumin and glutaraldehyde. We used a double
      balloon catheter as a temporary internal stent to create and seal the anastomosis
      during gluing. METHODS: Initially, anastomoses were made between cryopreserved
      human saphenous vein segments and coronary arteries in vitro on 12 intact bovine
      hearts. A total of 42 anastomoses were created with the catheter system
      introduced into the distal end of the graft, exiting the back wall, and entering
      the anterior wall of the coronary artery. Two balloons (one in the graft and one
      in the coronary artery) held the anastomosis stable while the biologic glue was
      applied externally and allowed to set for 2 minutes. The balloon catheter was
      then removed from the end of the graft simulating a side-to-side internal
      thoracic artery anastomosis. After the graft had been flushed to assure distal
      end patency, the open end of the graft was clipped, turning the anastomosis into
      an end-to-side graft. A pressure transducer was then attached to the graft and
      saline solution forcefully infused. RESULTS: All grafts easily held a pressure of
      300 mm Hg; 10 grafts were tested up to 560 mm Hg without leaks. Distal and
      proximal coronary artery patency was checked by examining flow out of the
      coronary ostia and by cutting arteries distal to the grafts. All anastomoses were
      patent on being opened and no glue was seen intraluminally. Subsequently, 3
      anastomoses of the left internal thoracic artery to the left anterior descending
      artery have been constructed in goats, with autopsies at 24 hours, 10 months, and
      1 year revealing patent anastomoses. CONCLUSION: A biologic glue and catheter
      system has been developed that allows a coronary anastomosis with a high bursting
      strength to be performed. When the system has been further developed and tested,
      truly minimally invasive heart surgery may be possible.

PMID- 10962408
TI  - Predicting long-term functional results after myocardial revascularization in
      ischemic cardiomyopathy.
AB  - OBJECTIVE: The goal of the present study was to define the early and late
      functional results after revascularization in ischemic cardiomyopathy and to
      identify variables predictive of a favorable outcome. METHODS: A retrospective
      review of all consecutive patients with ischemic cardiomyopathy undergoing
      myocardial revascularization between January 1991 and June 1998 was undertaken.
      One hundred sixty-seven patients (140 men) aged 60 +/- 8 years (range, 39-77
      years) with angina (n = 107), congestive heart failure (n = 54), or silent
      ischemia (n = 6) were identified. One hundred six (63%) patients with angina were
      in Canadian Cardiovascular Society class III or IV, and 40 (24%) patients with
      congestive failure were in New York Heart Association class III or IV. The
      preoperative left ventricular ejection fraction averaged 0.28 +/- 0.05 (range,
      0.16-0. 30). Thirteen (8%) patients required preoperative mechanical life
      support. A mean of 2.9 +/- 0.9 grafts per patient were performed, with an average
      myocardial ischemia time of 53 +/- 23 minutes and bypass time of 104 +/- 31
      minutes. RESULTS: There were 3 (1.7%) early deaths and 21 (13%) deaths during
      follow-up (2.7 +/- 2.1 years; range, 0.3-7.8 years), producing a survival of 94%
      +/- 2% and 75% +/- 10% at 1 and 5 years, respectively. Despite a significant
      increase in left ventricular ejection fraction (0.28 +/- 0.05 vs 0. 38 +/- 0.09,
      P =.0001), only 89 (54%) patients were symptom-free at follow-up. Freedom from
      recurrent angina was 98% +/- 1% and 81% +/- 8%, whereas freedom from congestive
      failure was 78% +/- 11% and 47% +/- 20% at 1 and 5 years, respectively. Follow-up
      New York Heart Association class in patients with congestive failure was improved
      (40/54 class III-IV vs 11/54 class III-IV, P =.0001). Multivariate analysis
      showed a lower ejection fraction (P =.01), preoperative congestive failure (P
      =.03), and a need for preoperative intra-aortic balloon pumping (P =.03) to be
      associated with a greater prevalence of recurrent congestive failure, whereas
      male sex (P =.01), preoperative angina (P =.04), use of the internal thoracic
      artery (P =.03), and higher number of grafts (P =.01) were associated with lower
      prevalence. Male sex (P =.06), higher number of grafts (P =.04), and shorter
      duration of myocardial ischemia (P =. 04) were also predictive of improvement in
      New York Heart Association class at follow-up. CONCLUSIONS: Despite satisfactory
      early and late survival, late functional outcome after myocardial
      revascularization in ischemic cardiomyopathy remains suboptimal because of
      recurrence or persistence of congestive failure. Selection of appropriate
      surgical candidates and extensive use of complete revascularization with the
      internal thoracic artery may substantially improve functional results.

PMID- 10962409
TI  - Primary endoleakage in endovascular treatment of the thoracic aorta: importance
      of intraoperative transesophageal echocardiography.
AB  - OBJECTIVES: Endovascular treatment of the thoracic aorta has developed as an
      efficacious alternative to open surgical repair. However, despite the high
      primary success rate, perigraft leakage constitutes the major concern in long
      term follow-up. Endoleaks are widely reported both in abdominal and thoracic
      endovascular series and are usually identified by intraoperative angiography.
      Transesophageal echocardiography is a sensitive imaging technique in the
      evaluation of aortic diseases, widely used to monitor cardiac surgery. The aim of
      this study was to evaluate the efficacy of transesophageal echocardiography in
      leakage detection during endovascular stent procedures of the thoracic aorta.
      METHODS: Intraoperative transesophageal echocardiography was used in conjunction
      with angiography in 25 patients subjected to endovascular stent treatment of the
      descending thoracic aorta. Spiral computed tomographic scanning was performed
      before discharge and 3, 6, and 12 months after treatment. RESULTS: Information
      from transesophageal echocardiography was relevant in the selection of the
      landing zone in 62% of cases. In 8 patients, transesophageal echocardiography
      with color Doppler sonography showed a perigraft leak, 6 of which were not
      visible on angiography, suggesting the need for further balloon expansion or
      graft extension. Postoperative computed tomographic scanning in the 25 patients
      showed 1 endoleak, which sealed spontaneously. At 3 months, computed tomographic
      examination confirmed the absence of perigraft leakage in all patients.
      CONCLUSIONS: During implantation of a stent-graft in the descending thoracic
      aorta, transesophageal echocardiography provides information in addition to that
      provided by angiography, improving immediate and late procedural results.

PMID- 10962410
TI  - Late angiographic result of using the right gastroepiploic artery as a graft.
AB  - OBJECTIVE: The angiographic patency of the right gastroepiploic artery graft used
      for coronary artery bypass grafting was studied during the late (5-10 years)
      postoperative period. METHODS: Among 936 patients undergoing a gastroepiploic
      artery graft for coronary artery bypass grafting between 1986 and 1999,
      postoperative angiographic restudy was conducted on 685 patients within 1 year
      (mean, 2.2 months), on 102 patients between 1 and 5 years (mean, 2.3 years), and
      on 52 patients between 5 and 10 years (mean, 7.8 years). RESULTS: The patency
      rate of the gastroepiploic artery graft was 94%, 88%, and 83% in each restudy
      group. The cumulative patency rate estimated by the Kaplan-Meier method was 96.6%
      at 1 month, 91.4% at 1 year, 80.5% at 5 years, and 62.5% at 10 years. Causes of
      late occlusion were primary anastomotic stenosis and anastomosis to a less
      critically stenosed coronary artery. Once the gastroepiploic artery was perfectly
      anastomosed to the coronary artery, which has tight stenosis and good runoff,
      late patency was good, and new stenosis in both the gastroepiploic artery trunk
      and the anastomotic site was uncommon. CONCLUSION: The gastroepiploic artery
      graft can be used effectively for coronary artery bypass for the long term with
      proper target selection.

PMID- 10962411
TI  - Reinfusion of mediastinal blood after heart surgery.
AB  - BACKGROUND: Several authors studying autotransfusion of shed mediastinal blood in
      patients undergoing heart operations have published conflicting results regarding
      reduction of the need for homologous blood transfusion. The effect on coagulation
      parameters is also unclear. METHODS: In a prospective randomized study, 198
      patients who underwent coronary artery bypass grafting or a valvular operation
      were divided into 2 groups: a group with autotransfusion of shed mediastinal
      blood after an operation and a control group. Continuous reinfusion of
      mediastinal blood was done until no drainage was present or for a period of 12
      hours after the operation. The amount of blood lost and autotransfused, the
      number of homologous blood products transfused, and the coagulation parameters
      were monitored. RESULTS: The number of patients requiring homologous blood
      transfusion was significantly different between the 2 groups (54/98 [55%] in
      autotransfused patients vs 73/100 [73%] in the control group, P =.01). The number
      of re-explorations for excessive bleeding was similar in the 2 groups (7/98
      [7.1%] vs 8/100 [8%]), but the amount of blood collected postoperatively was
      higher in the autotransfused patients compared with control patients (1200 +/-
      201 mL vs 758 +/- 152 mL, P =.0007). Coagulation parameters analyzed and
      complication rates were similar in the 2 groups after the operations. CONCLUSION:
      Autotransfusion of shed mediastinal blood reduces the need for homologous blood
      transfusion in patients undergoing various cardiac operations. The cause of
      increased shed blood in patients undergoing autotransfusion remains unclear.

PMID- 10962412
TI  - Health-related quality of life and post-traumatic stress disorder in patients
      after cardiac surgery and intensive care treatment.
AB  - OBJECTIVES: Health-related quality of life and patient satisfaction have become
      important end points in cardiac surgery. Post-traumatic stress disorder has been
      described in patients with life-threatening heart disease. In this study, we
      investigated the occurrence of post-traumatic stress disorder in a sample of
      patients after cardiac surgery and compared health-related quality of life and
      patient satisfaction between patients with and without evidence of post-traumatic
      stress disorder. METHODS: We studied 80 patients serially admitted to the
      intensive care unit after cardiac surgery (bypass grafting, n = 51; aortic valve
      replacement, n = 29). Health-related quality of life was assessed with the use of
      the SF-36 Health Status Questionnaire. Post-traumatic stress disorder was
      measured with a previously validated instrument (the Post-Traumatic Stress
      Syndrome 10-Questions Inventory), and 20 different aspects of life satisfaction
      were quantified on a scale ranging from 0 to 10. For measurements of health
      related quality of life and post-traumatic stress disorder, age- and gender
      comparable healthy individuals, as well as patients with cardiovascular diseases,
      served as control groups. RESULTS: Patients who had cardiac surgery described
      high life satisfaction summary scores (156 of a maximum of 200 points) and only
      small impairments in physical and mental SF-36 summary scores when compared with
      healthy control groups (median reduction 7.15, P <.05). Patients with evidence of
      post-traumatic stress disorder (n = 15) reported the lowest SF-36 mental health
      summary scores when compared with patients without stress disorder (38.3 vs 48.4,
      P =.004) and rated their life satisfaction lower (121.5 vs 162.0, P =.002).
      CONCLUSIONS: Patients who have had cardiac surgery demonstrate a high life
      satisfaction with an acceptable degree of physical and mental health-related
      quality of life. Impairments in psychosocial function and life satisfaction were
      found in a subgroup of patients with evidence of post-traumatic stress disorder.

PMID- 10962413
TI  - Effect of ischemic pretreatment on heat shock protein 72, neurologic outcome, and
      histopathologic outcome in a rabbit model of spinal cord ischemia.
AB  - OBJECTIVE: In the present study, we investigated the effect of ischemic
      pretreatment on heat shock protein 72 concentration and neurologic and
      histopathologic outcome after transient spinal cord ischemia. METHODS: In 28 New
      Zealand White rabbits, an aortic occlusion device was placed infrarenally. The
      animals were randomly assigned to 2 groups: ischemic pretreatment (n = 14
      animals) and control (n = 14 animals). The duration of ischemic pretreatment was
      6 minutes. After 24 hours, the aorta was occluded for 26 minutes in both groups
      of animals. Neurologic function was assessed 24 and 48 hours after the definite
      ischemic insult. At 48 hours, the animals were killed for histopathologic
      evaluation of the spinal cord. In a separate set of animals, heat shock protein
      72 levels were determined in the lumbar spinal cord after both a 6- and 10-minute
      ischemic period, with the use of a Western blot analysis. RESULTS: No significant
      difference in neurologic outcome between the groups was observed at 24 and 48
      hours. The incidence of paraplegia and severe paresis at 48 hours was 79% in the
      control group and 92% in the ischemic pretreatment group. There was no difference
      in histopathologic scores between the groups. Heat shock protein 72 could be
      clearly detected 1 and 2 days after 6- or 10-minute periods of spinal cord
      ischemia. CONCLUSIONS: In the present rabbit study, ischemic pretreatment could
      not induce tolerance against a moderately severe spinal cord ischemic insult,
      despite increased heat shock protein 72 levels after the preconditioning
      stimulus.

PMID- 10962414
TI  - Tranexamic acid compared with high-dose aprotinin in primary elective heart
      operations: effects on perioperative bleeding and allogeneic transfusions.
AB  - OBJECTIVE: Since excessive fibrinolysis during cardiac surgery is frequently
      associated with abnormal perioperative bleeding, many authors have advocated
      prophylactic use of antifibrinolytic drugs to prevent hemorrhagic disorders. We
      compared the effects of tranexamic acid (a synthetic antifibrinolytic drug) with
      aprotinin (a natural derivative product with antifibrinolytic properties) on
      perioperative bleeding and the need for allogeneic transfusions. METHODS: In a
      single-center prospective randomized unblinded trial, 1040 consecutive patients
      undergoing primary, elective cardiac operations with cardiopulmonary bypass
      received either high-dose aprotinin or tranexamic acid. The aprotinin group (518
      patients) received 280 mg in 20 minutes before the skin incision, 280 mg in the
      priming solution of the extracorporeal circuit, and a continuous infusion of 70
      mg/h throughout the operation. The tranexamic acid group (522 patients) received
      1 g in 20 minutes before the skin incision, 500 mg in the priming solution of the
      extracorporeal circuit, and a continuous infusion of 400 mg/h during the
      operation. Postoperative bleeding, perioperative transfusions, and hematologic
      variables were evaluated at fixed times. Postoperative thrombotic complications,
      intubation time, intensive care unit stay, and hospital stay were recorded.
      RESULTS: Postoperative bleeding was similar in the 2 groups: aprotinin 250 mL
      (150-400 mL) versus tranexamic acid 300 mL (200-450 mL) (median and 25th-75th
      quartiles), median difference of 50 mL (95% confidence intervals, 0-50 mL). The
      number of transfusions and the outcome did not differ. CONCLUSIONS: Tranexamic
      acid and aprotinin show similar clinical effects on bleeding and allogeneic
      transfusion in patients undergoing primary elective heart operations. Since
      tranexamic acid is about 100 times cheaper than aprotinin, its use is preferable
      in this type of patient.

PMID- 10962415
TI  - Experimental study of intermittent crossclamping with fibrillation and myocardial
      protection: reduced injury from shorter cumulative ischemia or intrinsic
      protective effect?
AB  - OBJECTIVE: During coronary artery revascularization, some surgeons favor
      intermittent crossclamping with ventricular fibrillation in preference to
      cardioplegic ischemic arrest for myocardial protection. It is unclear, however,
      whether intermittent crossclamping with fibrillation is equally protective or
      whether ischemic injury is reduced as a consequence of shorter cumulative
      ischemia. METHODS: We used isolated, Langendorff-perfused rat hearts, measured
      preischemic function (left ventricular developed pressure) with an
      intraventricular balloon, and then subjected the hearts to either (1) 40 minutes
      of global ischemia, (2) a 2-minute infusion of cardioplegic solution and 40
      minutes of ischemia, (3) multidose (every 10 minutes) infusions of cardioplegic
      solution during 40 minutes of ischemia, (4) continuous ventricular fibrillation
      during 40 minutes of ischemia, (5) intermittent (4 x 10 minutes) ischemia with 10
      minutes of reperfusion, (6) intermittent (4 x 10 minutes) ischemia preceded by
      intermittent cardioplegia, (7) intermittent (4 x 10 minutes) ischemia with
      ventricular fibrillation, (8) continuous (40 minutes) ventricular fibrillation
      during coronary perfusion, or (9) intermittent (4 x 10 minutes) ventricular
      fibrillation (with perfusion). All protocols were followed by 60 minutes of
      reperfusion. RESULTS: After 60 minutes of reperfusion, the percentage recovery of
      left ventricular developed pressure for groups 1 through 9 was as follows: 32% +/
      2%, 57% +/- 6%, 82% +/- 3%, 19% +/- 3%, 73% +/- 3%, 70% +/- 3%, 78% +/- 4%, 55%
      +/- 2%, and 57% +/- 3%, respectively. No significant differences were identified
      among groups 3, 5, and 7, but the percentage recovery of developed pressure in
      group 3 was significantly higher than that in group 6; the degree of recovery in
      groups 3 and 5 to 7 was significantly (P <.05) higher than in groups 1, 2, 4, 8,
      and 9. Early recovery was significantly (P <.05) more rapid in groups 3 and 5 to
      9, reaching a plateau (of 55%-80%) by 10 minutes of reperfusion; in groups 1, 2,
      and 4, the recovery plateau occurred after 50 minutes. Left ventricular end
      diastolic pressure was elevated in groups 1, 2, and 4 but was almost unchanged
      from baseline in the other groups. CONCLUSIONS: A similar level of myocardial
      protection was achieved with multidose (intermittent) cardioplegia or
      intermittent crossclamping (with or without fibrillation), indicating that
      intrinsic preservation by intermittent crossclamping with fibrillation does not
      exacerbate ischemic injury.

PMID- 10962416
TI  - The effects of heparin and extracorporeal circulation on platelet counts and
      platelet microaggregation during cardiopulmonary bypass.
AB  - BACKGROUND: Cardiopulmonary bypass is associated with platelet activation and
      reduced platelet counts. Platelet activation may artifactually lower platelet
      counts by causing aggregation. In vivo platelet activation may increase existent
      platelet microaggregation ex vivo. We studied platelet counts and existent
      platelet microaggregation at different stages of cardiopulmonary bypass. METHODS:
      Twenty-one patients were studied before and after heparinization (300 U. kg(-1))
      and at the end of cardiopulmonary bypass. Unaggregated (or single) platelets were
      counted in hirudin-anticoagulated blood, and total platelets were counted in
      ethylenediaminetetraacetic acid-anticoagulated blood. RESULTS: The total platelet
      count, 198 +/- 61 x 10(9). L(-1), was unaffected by heparin and stayed at 197 +/-
      60 x 10(9). L(-1) (P =.7) but fell during extracorporeal circulation; the
      hemodilution-corrected count was 163 +/- 52 x 10(9). L(-1) (P =.0004).
      Heparinization reduced the unaggregated platelet count from (mean +/- 1 SD) 178
      +/- 62 x 10(9). L(-1) to 155 +/- 60 x 10(9). L(-1) (P =.0001). Extracorporeal
      circulation had little additional effect. The hemodilution-corrected count was
      142 +/- 48 x 10(9). L(-1) (P =.6). CONCLUSIONS: Heparinization caused platelet
      activation and increased existent platelet microaggregation ex vivo. During
      extracorporeal circulation, there was a reduction in total platelets that was
      greater than could be explained by hemodilution alone, but the unaggregated
      platelet count did not change significantly when corrected for hemodilution.
      Furthermore, the increased platelet microaggregation observed after
      heparinization was no longer evident after this loss. These findings suggest that
      during extracorporeal circulation, the platelets that formed into microaggregates
      after heparinization were lost from the circulation in preference to single
      platelets.

PMID- 10962417
TI  - The effects of retrograde cardioplegia technique on myocardial perfusion and
      energy metabolism: a magnetic resonance imaging and localized phosphorus 31
      spectroscopy study in isolated pig hearts.
AB  - OBJECTIVE: The present work was designed to study the myocardial perfusion and
      energy metabolism during retrograde cardioplegia performed with different
      methods, including deep coronary sinus cardioplegia, coronary sinus orifice
      cardioplegia, and right atrial cardioplegia. METHODS: Isolated pig hearts were
      subjected to antegrade cardioplegia, right atrial cardioplegia, deep coronary
      sinus cardioplegia, and coronary sinus orifice cardioplegia in a random order.
      Cardioplegic distribution was assessed by T1-weighted magnetic resonance imaging
      in 1 group of hearts (n = 8). The flow dynamics of cardioplegia were assessed by
      T2*-weighted imaging in a second group of hearts (n = 8). RESULTS: T1-weighted
      images revealed an apparent perfusion defect in the posterior wall of the left
      ventricle, the posterior portion of the interventricular septum, and the right
      ventricular free wall during deep coronary sinus cardioplegia. The perfusion
      defect observed in the first 2 regions with deep coronary sinus cardioplegia
      resolved with coronary sinus orifice cardioplegia. Right atrial cardioplegia
      provided the most homogeneous perfusion to all regions of the myocardium relative
      to the other 2 retrograde cardioplegia modalities. T2*-weighted images showed
      that the 3 retrograde cardioplegia modalities provided similar cardioplegic flow
      velocities. Localized phosphorus 31 spectroscopy showed that the levels of
      adenosine triphosphate and phosphocreatine were significantly lower in the
      posterior wall (adenosine triphosphate, 42.86% +/- 5.91% of its initial value;
      phosphocreatine, 11.43% +/- 11.3%) than the anterior wall (adenosine
      triphosphate, 89.19% +/- 8.83%; phosphocreatine, 59.54% +/- 12.58%) of the left
      ventricle during 70 minutes of normothermic deep coronary sinus cardioplegia.
      CONCLUSIONS: Deep coronary sinus cardioplegia results in myocardial ischemia in
      the posterior wall of the left ventricle and the posterior portion of the
      interventricular septum, as well as in the right ventricular free wall. Coronary
      sinus orifice cardioplegia improves cardioplegic distribution in these regions.
      Relative to deep coronary sinus cardioplegia and coronary sinus orifice
      cardioplegia, right atrial cardioplegia provides the most homogeneous perfusion.

PMID- 10962418
TI  - Aprotinin administration in the pericardial cavity does not prevent platelet
      activation.
AB  - OBJECTIVES: Aprotinin is frequently administered systemically to patients
      undergoing cardiopulmonary bypass to inhibit activation of platelets and plasma
      protein systems and thus reduce postoperative blood loss. Two reports on local
      aprotinin administration, that is, into the pericardial cavity, also indicated
      improvement in postoperative blood loss, but the underlying mechanism was not
      investigated. We previously reported the disappearance of glycoprotein Ib from
      the platelet surface and the appearance of platelet-derived microparticles in the
      pericardial cavity of patients undergoing cardiopulmonary bypass as signs of
      platelet activation. Here, we investigated whether such local aprotinin
      administration reduced platelet activation. METHODS: In a double-blind study, 6
      patients received aprotinin (500,000 KIU) into the pericardial cavity during the
      operation and 7 patients received a placebo. Platelet surface glycoprotein Ib
      expression, concentration of microparticles, and concentration of complexes of
      platelets with leukocytes, erythrocytes, or each other, were measured by flow
      cytometry. RESULTS: We confirmed the reduced glycoprotein Ib expression and the
      increased concentration of microparticles in the pericardial cavity, as
      previously reported, and found no increased concentration of platelet complexes.
      However, no differences between aprotinin and placebo treatments were observed in
      these platelet activation parameters in the pericardial cavity or the systemic
      circulation. CONCLUSION: We conclude that administration of aprotinin into the
      pericardial cavity during cardiopulmonary bypass and at concentrations similar to
      the systemic application does not reduce platelet activation in that compartment
      or the systemic circulation.

PMID- 10962419
TI  - P-selectin participates in cardiopulmonary bypass-induced inflammatory response
      in association with nitric oxide and peroxynitrite production.
AB  - OBJECTIVES: P-selectin participates in the development of inflammatory disorders.
      Cardiopulmonary bypass is thought to induce inflammatory response and increase
      nitric oxide production. To evaluate the role of P-selectin in bypass-induced
      inflammatory response and its association with nitric oxide production, we
      examined the effect of P-selectin monoclonal antibody in a rat model of
      cardiopulmonary bypass. METHODS: Twenty adult Sprague-Dawley rats undergoing
      cardiopulmonary bypass for 60 minutes were divided into 2 groups. A 3-mg/kg dose
      of anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo
      Pharmaceuticals, Osaka, Japan) was administered into the priming solution before
      bypass in group P (n = 10) and a 3-mg/kg dose of PNB1.6 (nonblocking monoclonal
      antibody) was added in group C for control (n = 10). RESULTS: At the termination
      of bypass and 3 hours after the termination of bypass, plasma levels of
      interleukins 6 and 8, nitrate/nitrite, the percentage ratio of nitrotyrosine to
      tyrosine (an indicator of peroxynitrite formation), and the respiratory index
      were significantly higher than before bypass in both groups, and they were
      significantly lower in group P than in group C. Plasma P-selectin level in group
      C and exhaled nitric oxide concentration in both groups at termination of bypass
      were significantly lower than those before bypass, and they were significantly
      higher 3 hours after termination of bypass than before bypass in both groups.
      Plasma P-selectin level and exhaled nitric oxide concentration in group P were
      significantly higher than those in group C at the end of bypass, but they were
      significantly lower 3 hours after the termination of bypass. CONCLUSIONS: These
      results demonstrate that P-selectin may participate in the augmentation of bypass
      induced inflammatory response in association with nitric oxide and peroxynitrite
      production.

PMID- 10962420
TI  - Low-potassium dextran solution ameliorates reperfusion injury of the lung and
      protects surfactant function.
AB  - OBJECTIVE: This study was designed to compare the effect of lung preservation
      with low-potassium dextran solution and Euro-Collins solution on reperfusion
      injury and surfactant function by using an in situ model of warm ischemia.
      METHODS: The left lungs of 6 minipigs were selectively perfused with Euro-Collins
      solution. In an additional 6 animals low-potassium dextran solution was used for
      flush perfusion. After 90 minutes of warm ischemia, the lungs were reperfused,
      and the contralateral pulmonary artery and bronchus were clamped. Hemodynamic and
      respiratory measurements were obtained for 7 hours of reperfusion. Surface
      tension of bronchoalveolar lavage and surfactant small and large aggregates were
      determined before perfusion (right lung) and after 2 hours of reperfusion (left
      lung). RESULTS: In the group receiving Euro-Collins solution, right heart failure
      developed within 215 +/- 39 minutes of reperfusion. An increase in minimal
      surface tension (P =.03), surfactant small aggregates/large aggregates ratio (P
      =.003), and bronchoalveolar lavage protein content (P =.012) were found after 2
      hours of reperfusion. In the group receiving low-potassium dextran solution, all
      minipigs survived (P =.0001). Dynamic lung compliance (P =.034) and oxygen
      tension/inspired oxygen fraction ratios were higher (P =. 0001). Lung water
      content was lower (P =.049). The increase of minimal surface tension (P =.02) and
      bronchoalveolar lavage protein concentration (P =.015) were significantly less.
      CONCLUSION: Preservation of the lung with Euro-Collins solution leads to a
      reduction of physical surfactant function during reperfusion. Low-potassium
      dextran solution protects surfactant function and metabolism, thereby reducing
      reperfusion injury of the lung.

PMID- 10962421
TI  - Inhibition of angiotensin-converting enzyme by captopril: a novel approach to
      reduce ischemia-reperfusion injury after lung transplantation.
AB  - OBJECTIVES: Ischemia-reperfusion injury after lung transplantation involves the
      generation of free radicals. Captopril has been shown to be protective in models
      of ischemia-reperfusion injury in other organs by acting as a free radical
      scavenger. The purpose of this study was to assess the protective effects of
      captopril against ischemia-reperfusion injury and to evaluate the ability of
      captopril to scavenge free radicals and inhibit neutrophil activation in an
      experimental model of lung transplantation. METHODS: A rat single-lung transplant
      model was used. Donor lungs were flushed and preserved in low-potassium dextran
      glucose solution with (n = 5) and without captopril (500 micromol/L; n = 5) for
      18 hours at 4 degrees C and then transplanted and reperfused for 2 hours. At the
      conclusion of the 2-hour reperfusion period, arterial blood gases, blood
      pressure, and peak airway pressure were measured. Lung tissue biopsy specimens
      were obtained for assessment of wet/dry weight ratios, histology, and neutrophil
      sequestration (myeloperoxidase activity). Lipid peroxidation (F(2)-isoprostane
      assay) was analyzed from plasma samples and tissue lysates. RESULTS: The addition
      of captopril to the lung preservation solution significantly improved
      postreperfusion PO (2) (312 +/- 63.3 mm Hg vs 202 +/- 21.1 mm Hg; P =.006), peak
      airway pressure (11.4 +/- 1.1 cm H(2)O vs 15.6 +/- 1.5 cm H(2)O; P =.001), and
      wet/dry weight ratio (4.9 +/- 0.4 vs 15.8 +/- 10.9; P =.008). Blood pressures did
      not differ significantly between groups. No significant differences were seen in
      myeloperoxidase activity or F(2)-isoprostane levels. CONCLUSIONS: The use of
      captopril in the preservation solution ameliorates ischemia-reperfusion injury in
      transplanted lungs after an extended cold preservation period. The mechanisms by
      which captopril is protective remain elusive but do not appear to include
      inhibition of neutrophil sequestration or lipid peroxidation. This novel approach
      to ischemia-reperfusion injury may lead to improved lung function after
      transplantation and provide further insight into the pathogenesis of acute lung
      injury.

PMID- 10962422
TI  - Adenovirus-mediated genetic manipulation of the myocardial beta-adrenergic
      signaling system in transplanted hearts.
AB  - OBJECTIVES: Ex vivo perfusion of the cardiac allograft during organ procurement
      is an ideal environment for adenoviral vectors with transgenes that target
      improving graft contractility. One such target is the beta-adrenergic receptor
      signaling system, in which alterations in transgenic mice have elucidated novel
      means to improve the function of the heart in vivo. The purpose of the current
      study was to determine the functional consequences of beta-adrenergic receptor
      manipulation in a rabbit model of cardiac allograft transplantation. METHODS: New
      Zealand White rabbits weighing 3 kg served as recipients to 1-kg outbred donors.
      Donor hearts were arrested and harvested, and 1 of 3 adenoviral constructs was
      administered into the aortic root perfusing the graft. Transgenes delivered
      encoded either the human beta(2)-adrenergic receptor, a peptide inhibitor of beta
      adrenergic receptor densensitization, or the marker transgene beta-galactosidase.
      RESULTS: Five days after cervical heterotopic transplantation, left ventricular
      performance was measured on a Langendorff apparatus. A moderate pattern of
      rejection was seen in all grafts. Biventricular myocyte expression of beta
      galactosidase was observed, and beta(2)-adrenergic receptor density was elevated
      10-fold in grafts that received adeno-beta(2)-adrenergic receptor. Left
      ventricular systolic and diastolic performance was significantly increased in
      grafts transfected with either adeno-beta(2)-adrenergic receptor or adeno-beta
      adrenergic receptor densensitization compared with control grafts that received
      adeno-beta-galactosidase. CONCLUSIONS: Ex vivo adenovirus-mediated gene transfer
      is feasible in a rabbit allograft model and, more important, genetic manipulation
      of beta-adrenergic receptor signaling either by increasing beta(2)-adrenergic
      receptor density or blocking endogenous receptor desensitization improves graft
      function acutely in this allograft model.

PMID- 10962423
TI  - Factors influencing arterial oxygenation early after bidirectional cavopulmonary
      shunt without additional sources of pulmonary blood flow.
AB  - OBJECTIVES: Although the arterial oxygen saturation after bidirectional
      cavopulmonary shunting should theoretically be homogeneous if additional
      pulmonary flow is obliterated, the arterial oxygen saturation has been found to
      vary in clinical practice. Knowledge of the preoperative and operative
      determinants of arterial oxygen saturation early after bidirectional
      cavopulmonary shunting may lead to a better understanding of this unique
      physiology. METHODS: Thirty-five patients who underwent bidirectional
      cavopulmonary shunting with obliteration of additional pulmonary flow were
      included in this study. The arterial oxygen saturation was determined at the 5
      time points over a 48-hour period. Multivariable regression analysis was used to
      identify the independent predictors of the arterial oxygen saturation. RESULTS:
      No significant interval changes occurred in the arterial oxygen saturation during
      the 48 hours after bidirectional cavopulmonary shunting, which ranged from 61.6%
      to 95.6%. There was a significant inverse correlation between the postoperative
      superior vena cava pressure and the arterial oxygen saturation (P =.003). A low
      arterial oxygen saturation early after bidirectional cavopulmonary shunting was a
      predictor of mortality or exclusion from univentricular repair within 24 months
      (P =.012, odds ratio = 1.14). Of 11 factors identified by univariable analysis,
      multiple regression analysis indicated that age less than 8 months at the time of
      shunting (P <.0001) and ventricular volume overload (P =. 002) predicted a lower
      arterial oxygen saturation after bidirectional cavopulmonary shunting.
      CONCLUSIONS: Even without additional sources of pulmonary blood flow, several
      preoperative factors, including younger age and severe ventricular volume
      overload, predicted a decrease in the arterial oxygen saturation early after
      bidirectional cavopulmonary shunting. This, in turn, predicted poor outcome
      during 2 years of follow-up.

PMID- 10962424
TI  - Procollagen synthesis by fresh and cryopreserved rat pulmonary valve grafts.
AB  - OBJECTIVE: Allograft valves are frequently used in the repair of congenital
      cardiac anomalies. The failure rate may differ depending on the type of allograft
      used. Previous studies have shown that rat aortic valve grafts exhibit synthesis
      of procollagen, suggesting a capacity for repair and regeneration after
      implantation. No studies of pulmonary valve grafts in the heterotopic rat implant
      model have thus far been reported. This study was designed to investigate whether
      pulmonary valve grafts maintain in vivo viability, as demonstrated by procollagen
      synthesis, and whether cryopreservation, histocompatibility, or both affect this
      property. METHODS: Cryopreserved and fresh rat pulmonary valves were implanted
      into the abdominal aorta of syngeneic and allogeneic recipients. The grafts and
      native valves were excised 3 to 21 days after implantation. Valves were sectioned
      and immunohistochemically stained for procollagen. Computerized morphometry was
      used to calculate changes in intima, media, and adventitia as a percentage of
      cross-sectional area of the graft. Procollagen content was graded by
      semiquantitative methods. RESULTS: Pulmonary valve grafts had significantly
      greater collagen density in the intima and adventitia compared with native aortic
      and pulmonary tissues, but collagen density in the media was similar in all
      groups. The grafts demonstrated appreciably greater procollagen than the
      corresponding native valves. These findings were consistent in all grafts (ie,
      both fresh and cryopreserved, both syngeneic and allogeneic), irrespective of
      duration of implantation. CONCLUSIONS: Procollagen synthesis occurs in pulmonary
      valve grafts early after implantation, indicating viability of these tissues.
      This model of pulmonary valve implantation may have wide applicability to
      questions of allograft biology.

PMID- 10962426
TI  - Does acquired angioedema increase the risk of surgery with cardiopulmonary
      bypass?

PMID- 10962425
TI  - Triiodothyronine repletion in infants during cardiopulmonary bypass for
      congenital heart disease.
AB  - OBJECTIVE: Cardiopulmonary bypass suppresses circulating thyroid hormone levels.
      Although acute triiodothyronine repletion has been evaluated in adult patients
      after cardiopulmonary bypass, triiodothyronine pharmacokinetics and effects have
      not previously been studied in infants undergoing operations for congenital heart
      disease. We hypothesized that triiodothyronine deficiency in the developing heart
      after bypass may adversely affect cardiac function reserve postoperatively.
      METHODS: Infants less than 1 year old undergoing ventricular septal defect or
      tetralogy of Fallot repair were randomized into 2 groups. Group T (n = 7)
      received triiodothyronine (0.4 microg/kg) immediately before the start of
      cardiopulmonary bypass and again with myocardial reperfusion. Control (NT, n = 7)
      patients received saline solution placebo or no treatment. RESULTS: These groups
      underwent similar ischemic and bypass times and received similar quantities of
      inotropic agents after the operation. The NT group demonstrated significant
      depression in circulating levels, compared with prebypass levels, for free
      triiodothyronine and total triiodothyronine at 1, 24, and 72 hours after bypass.
      Group T demonstrated similar low thyroxine values, but free and total
      triiodothyronine levels were maintained at prebypass levels for 24 hours and
      remained elevated over those of group NT (P <.05) at 72 hours. Heart rate was
      transiently elevated in group T compared with group NT (P <.05), and peak
      systolic pressure-rate product increased after 6 hours. CONCLUSION: These data
      imply that (1) triiodothyronine in the prescribed dose prevents circulating
      triiodothyronine deficiencies and (2) triiodothyronine repletion promotes
      elevation in heart rate without concomitant decrease in systemic blood pressure.
      Elevation of peak systolic pressure-rate product implies that triiodothyronine
      repletion improves myocardial oxygen consumption and may enhance cardiac function
      reserve after cardiopulmonary bypass in infants.

PMID- 10962427
TI  - Lymphocyte-rich pleural liposarcoma mimicking pericardial cyst.

PMID- 10962428
TI  - Norwood/Batista operation for a newborn with dilated myopathy of the left
      ventricle.

PMID- 10962429
TI  - Assessment of sternal vascularity with single photon emission computed tomography
      after harvesting of the internal thoracic artery.

PMID- 10962431
TI  - A pitfall of reusing disposable apparatus for endoscopic surgery.

PMID- 10962432
TI  - Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) in humans.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant
      heterocyclic amine formed in meat and fish during cooking and can be used as a
      model compound for this class of chemicals possibly involved in human
      carcinogenesis. Knowing the exposure to heterocyclic amines is important for
      establishing their role in human diseases. Serum albumin (SA) and globin (Gb)
      adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344
      rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected
      24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis
      was analyzed by gas chromatography-mass spectrometry or liquid chromatography
      tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the
      dose. Studies on 35 volunteers with different dietary habits exhibited that diet
      was a major determinant in the formation of both adducts. PhIP-SA adducts were
      significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7
      +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test).
      The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in
      meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different
      in smokers and in non-smokers. The results show for the first time that PhIP
      blood protein adducts are present in humans not given the synthetic compound.
      Both biomarkers appear to be suitable for assessing dietary exposure and internal
      PhIP dose and may be promising tools for studying the role of heterocyclic amines
      in the etiology of colon cancer and other diseases.

PMID- 10962433
TI  - Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the
      carcinogen delta-aminolevulinic acid.
AB  - Well known are the anti-oxidant, free radical-scavenging and anti-tumorigenic
      properties of melatonin. delta-Aminolevulinic acid (ALA) is a precursor of heme
      synthesis. When over-produced and accumulated in tissues, ALA is a potential
      carcinogen, such as in the course of acute intermittent porphyria, hereditary
      tyrosinemia and lead poisoning. Our aim was to examine the potential protective
      effect of melatonin against oxidative damage to nuclear DNA and membrane lipids
      in rat lung and spleen caused by ALA. Changes in 8-hydroxy-2;-deoxyguanosine (8
      OHdG) levels, an index of DNA damage, and the level of malondialdehyde + 4
      hydroxyalkenals, an index of lipid peroxidation, were measured. Rats were
      injected with ALA (i.p., 40 mg/kg body weight, every other day) and/or with
      melatonin (i.p., 10 mg/kg body weight, 3 times daily) for 2 weeks. Both 8-OHdG
      and lipid peroxidation levels increased significantly in lung and spleen due to
      ALA treatment. Co-treatment with melatonin completely counteracted the effects of
      ALA. In conclusion, melatonin effectively protects nuclear DNA and lipids in rat
      lung and spleen against oxidative damage caused by the carcinogen ALA, and the
      indole may be of value as a supplement in patients suffering from molecular
      damage related to ALA accumulation.

PMID- 10962434
TI  - Syndecan-1 expression is up-regulated in pancreatic but not in other
      gastrointestinal cancers.
AB  - Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan
      sulfate proteoglycans, which participate in cell proliferation, cell migration
      and cell-matrix interactions. Decreased expression of syndecan-1 has been
      observed in some gastrointestinal malignancies, and it is thought that high
      levels of syndecan-1 correlate with the maintenance of epithelial morphology and
      inhibition of invasiveness. In our study, we characterized the expression of
      syndecan-1 in normal, chronic pancreatitis and primary and metastatic human
      pancreatic cancer tissues, in cultured pancreatic cancer cell lines and in
      esophageal, gastric, colon, and liver cancers. Pancreatic cancer cell lines
      expressed syndecan-1 mRNA and protein at variable levels. In addition, these
      cells also released syndecan-1 into the culture medium. Pancreatic cancer tissues
      markedly over-expressed syndecan-1 mRNA in comparison with both chronic
      pancreatitis (2.4-fold increase, p < 0.01) and normal pancreatic samples (10.6
      fold increase, p < 0.01). There was no difference in syndecan-1 mRNA expression
      between early and advanced tumors. By in situ hybridization and
      immunohistochemistry, syndecan-1 expression was evident at relatively low levels
      in the ductal cells and less frequently in acinar cells of the normal pancreas.
      In chronic pancreatitis, syndecan-1 was present at low to moderate levels in
      areas with atrophic acinar cells and ductular complexes. In contrast, in
      pancreatic cancer tissues, syndecan-1 was present at moderate to high levels in
      the majority of the cancer cells within the tumor mass and also in metastatic
      lesions of pancreatic tumors. Syndecan-1 mRNA levels in other gastrointestinal
      malignancies (esophageal, gastric, colon and liver cancers) were not
      significantly different from the levels observed in the corresponding normal
      samples. Together, our findings suggest that syndecan-1 expression by pancreatic
      cancer cells may be of importance in the pathobiology of this disorder and that
      its role in pancreatic cancer seems to be different from that in other
      gastrointestinal malignancies.

PMID- 10962435
TI  - Expression of emmprin (CD147), a cell surface inducer of matrix
      metalloproteinases, in normal human brain and gliomas.
AB  - EMMPRIN (extracellular matrix metalloproteinase inducer), also called CD147,
      basigin or M6 in the human, is a member of the immunoglobulin superfamily that is
      present on the surface of tumor cells and stimulates adjacent fibroblasts to
      produce matrix metalloproteinases (MMPs). In our study, we investigated
      expression of EMMPRIN in human normal brain and gliomas, since mouse basigin and
      chicken HT7, the species homologues of human EMMPRIN, are associated with
      neuronal interactions and normal blood-brain barrier function, respectively.
      EMMPRIN expression was detected in all samples of non-neoplastic brain and glioma
      tissues examined. However, expression levels of EMMPRIN mRNA and protein were
      significantly higher in gliomas than in non-neoplastic brain. Moreover, levels of
      mRNA expression and immunohistochemical staining correlated with tumor
      progression in gliomas: They were highest in the most malignant form of glioma,
      glioblastoma multiforme, followed by anaplastic astrocytoma and then low-grade
      astrocytoma. Also, immunolocalization revealed quite different distributions in
      non-neoplastic brain and glioma: EMMPRIN was demonstrated only in vascular
      endothelium in non-neoplastic regions of the brain, whereas it was present in
      tumor cells but not in proliferating blood vessels in malignant gliomas. These
      data indicate that an MMP inducer molecule EMMPRIN is differently expressed in
      human normal brain and gliomas and could be associated with astrocytoma
      progression. Possible mechanisms whereby glioma cell EMMPRIN could influence
      tumor progression will be discussed.

PMID- 10962437
TI  - Proliferation, apoptosis, and manganese superoxide dismutase in malignant
      mesothelioma.
AB  - Proliferation and apoptotic indices of tumour cells may have important prognostic
      significance. Manganese superoxide dismutase (MnSOD), an important anti-oxidant
      enzyme, has been shown to decrease proliferation of malignant cells transfected
      with the MnSOD gene. The aim of the present study was to investigate the indices
      of cell proliferation and apoptosis and their prognostic significance in human
      mesothelioma and to assess the effect of MnSOD on the proliferation and apoptosis
      of the mesothelioma cells expressing high constitutive MnSOD activity. Tissue
      sections from 35 subjects with malignant pleural mesothelioma were studied for
      cell proliferation by Ki-67 immunohistochemistry and for apoptosis by the TUNEL
      assay. In additional experiments, 2 mesothelioma cell lines expressing either low
      (M14K) or high (M38K) MnSOD levels were assessed for proliferative and apoptotic
      responses to epirubicin. The median proliferation and apoptotic indices of the
      mesothelioma tissue were 8.2% and 0.75%, respectively. Patients with a high
      proliferation (>8%) or apoptotic index (>0.75%) showed a worse prognosis (p <
      0.001). MnSOD expression was inversely correlated with cell proliferation (p =
      0.02). Our cell line experiments indicated that cells expressing high MnSOD
      levels were more resistant to apoptosis and showed lower proliferation when
      exposed to epirubicin in vitro. These findings show that high proliferation and
      apoptosis are associated with a poor prognosis of mesothelioma and that a high
      MnSOD level is associated with low proliferation of tumour cells. Furthermore,
      experiments with cultured mesothelioma cells suggest the importance of MnSOD in
      the proliferation and apoptosis caused by drug exposure.

PMID- 10962436
TI  - Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast
      carcinomas.
AB  - Breast cancer is one of the most common malignancies among women. The molecular
      mechanisms involved in breast carcinogenesis, however, remain to be elucidated.
      Although somatic mutation of BRCA1 is rare, BRCA1 protein expression is reduced
      in about 30% of sporadic breast carcinomas (Yoshikawa et al., Clin. Cancer Res.,
      5:1249-1261, 1999), indicating its possible involvement even in sporadic breast
      carcinogenesis. Among the BRCA1-interactive proteins are hRAD51 (a human
      homologue of Escherichia coli rec A protein), BARD1 (BRCA1-associated RING domain
      1) and p53, all of which are involved in DNA repair. We have analyzed the
      expression patterns of the hRAD51, BARD1 and p53 proteins in five breast cancer
      cell lines, including a BRCA1-deficient cell line, and in 179 breast cancer
      tissue samples from Japanese women, including 113 sporadic, 47 hereditary (i.e.,
      BRCA1 status unknown), and 19 BRCA1-associated cases. Of the 179 breast
      carcinomas, fifty-four (30%) exhibited reduced hRAD51 expression, and sixty-two
      (35%) exhibited p53 overexpression. On the other hand, reduced expression level
      of BARD1, and of hMSH2 and hMLH1, which are components of DNA mismatch-repair
      pathway and are involved in colorectal carcinogenesis, was observed respectively
      in only 10 (6%), 8 (5%) and 3 (2%) cases. The overall frequency of sporadic
      breast carcinomas with abnormal expression of either BRCA1 or the BRCA1
      interactive proteins was 67% (76/113). These results indicate that there may be
      an important role for the BRCA1-associated DNA-repair pathway, not only in BRCA1
      associated breast carcinomas, but also in sporadic breast carcinomas.

PMID- 10962438
TI  - RAS transformation causes sustained activation of epidermal growth factor
      receptor and elevation of mitogen-activated protein kinase in human mammary
      epithelial cells.
AB  - Activation of the ras oncogene is an important step in carcinogenesis. Human MCF
      10A mammary epithelial cells were transformed with a point-mutated form of the Ha
      ras oncogene. Epidermal growth factor receptor (EGFR) phosphorylation levels were
      chronically elevated after EGF induction and the EGFR ligand-driven
      internalization rate was slower in Ha-ras transformed MCF-10A cells.
      Additionally, basal levels of p42/44 mitogen-activated protein kinase (MAPK)
      expression and enzyme activity were significantly higher in Ha-ras transformed
      cells, localized predominantly in the nucleus. The anti-EGFR monoclonal antibody
      (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 blocked anchorage
      independent growth of Ha-ras transformed cells in soft agar and were more
      effective when used in combination. The MEK inhibitor PD98059 and anti-erbB-2 MAb
      L26 also suppressed colony formation of Ha-ras transformed cells in soft agar.
      Therefore, Ha-ras transformation leads to an augmentation in signaling through
      the EGFR as a result of an increase in ligand-dependent phosphorylation, a
      decrease in its internalization and an up-regulation in basal p44/42 MAPK levels.
      These effects may contribute to uncontrolled growth of Ha-ras-transformed human
      mammary epithelial cells.

PMID- 10962439
TI  - Reduced cell migration, tumor growth and experimental metastasis of rat F-11
      cells whose expression of GD3-synthase is suppressed.
AB  - We previously established a rat F-11 cell line whose expression of ganglioside
      GD3 was inhibited by stable transfection of the anti-sense vector against the GD3
      synthase gene, showing that specific inhibition of GD3-synthase expression in
      tumor cells greatly reduced their growth rate in nude mice. Here, we report that
      down-regulation of GD3-synthase expression in anti-sense-transfected F-11 cells
      correlates with reduced cell migration and invasion in vitro and tumor growth and
      metastasis in vivo. When cultures were denuded of cells in a 1-mm-wide strip, the
      anti-sense-transfected F-11 cells migrated very slowly into the denuded area.
      Differences in migration between anti-sense-transfected cells and control
      parental cells were easily apparent. In vitro invasion assay of F-11 cells
      revealed a 3-fold decrease in invasion ability from the GD3-synthase-suppressed
      cells; colony formation in soft agar was not affected. Injection (i.v.) of
      control sense-transfected and untransfected F-11 cells resulted in multiple,
      large metastatic nodules in each of the 12 mice, whereas i.v. injection of anti
      sense-transfected F-11 cells formed a single, small metastatic nodule in only 2
      of the 8 nude mice. In addition, even if metastasis occurred, the anti-sense
      induced metastatic nodules were much smaller than the metastatic nodules formed
      by control F-11 cells. These results demonstrate that suppression of GD3-synthase
      expression, which results primarily in a marked decrease in the concentration of
      ganglioside GD3, greatly reduces cell spreading, invasion and both the incidence
      and growth rate of experimental metastasis of F-11 cells.

PMID- 10962440
TI  - Beta-galactoside alpha2,6 sialyltransferase in human colon cancer: contribution
      of multiple transcripts to regulation of enzyme activity and reactivity with
      Sambucus nigra agglutinin.
AB  - Colon cancer tissues display an increased activity of beta-galactoside alpha2,6
      sialyltransferase (ST6Gal.I) and an increased reactivity with the lectin from
      Sambucus nigra (SNA), specific for alpha2,6-sialyl-linkages. Experimental and
      clinical studies indicate a contribution of these alterations to tumor
      progression, but their molecular bases are largely unknown. In many tissues,
      ST6Gal.I is transcriptionally regulated through the usage of different promoters
      that originate mRNAs diverging in the 5;-untranslated regions. RT-PCR analysis of
      14 carcinoma samples, all expressing an increased ST6Gal.I enzyme activity, and
      of the corresponding normal mucosa revealed the presence of at least 2
      transcripts. One, containing the 5;-untranslated exons, Y+Z, is thought to
      represent the "housekeeping" expression, and another previously described in
      hepatic tissues. Both the Y+Z and the hepatic transcripts were detectable in
      normal and cancer tissues but that latter form had a marked tendency to
      accumulate in cancer. The extent of alpha2,6-sialylation of glycoconjugates, as
      determined by SNA-dot blot analysis, was markedly enhanced in all cancer
      specimens, but the level of reactivity only partially correlated with the level
      of enzyme expression. Western blot analysis revealed a strikingly heterogeneous
      pattern of SNA reactivity among cancer tissues. These data indicate that: i)
      during neoplastic transformation of colonic cells, ST6Gal.I expression may be
      modulated through a differential promoter usage; ii) the extent of alpha2,6
      sialylation of cancer cell membranes is not a direct function of the ST6Gal.I
      activity, strongly suggesting the existence of other, more complex mechanisms of
      regulation.

PMID- 10962441
TI  - Differential expression of p73 splice variants and protein in benign and
      malignant ovarian tumours.
AB  - The p73 gene encodes a protein with substantial structural and functional
      similarities to the tumour-suppressor p53. Alternative splicing of p73 mRNA leads
      to expression of 6 known RNA species and proteins (alpha, beta, gamma, delta,
      epsilon, zeta). We analysed the expression of these splice variants in ovarian
      adenocarcinoma by RT-PCR followed by detection of amplicons with the Southern
      technique and by immunoblot in 32 malignant and benign epithelial ovarian tumour
      specimens and 3 ovarian adenocarcinoma cell lines (A2780, 2008, OVCAR-3).
      p73alpha mRNA was expressed in all 17 ovarian cancer specimens, and 14 of 17
      expressed at least 3 splice variants. In contrast, a different expression pattern
      was present in the ovarian adenomas: p73alpha was detected in 6 of 12 benign
      tumours, and only 1 adenoma expressed 3 splice variants. p73 protein was
      expressed in 9 of 16 ovarian cancer specimens, in all cell lines and in 1 of 3
      borderline tumours. In contrast, none of 9 ovarian adenomas expressed detectable
      amounts of p73 protein. Expression of p73 mRNA and protein was not correlated
      with FIGO stage and histological grade, but we observed a significant correlation
      with over-expression of p53 protein. In summary, epithelial ovarian cancers
      express a more complex p73 isoform pattern and higher levels of p73 mRNA and
      protein than ovarian adenomas.

PMID- 10962443
TI  - p53 mutational spectra are different between squamous-cell carcinomas of the lip
      and the oral cavity.
AB  - We studied the p53 mutational spectra of 34 lip and 60 intra-oral squamous-cell
      carcinomas and examined possible etiological and prognostic correlations for
      these tumor sites. For the p53 analysis of exons 5-8, we used PCR/TGGE screening
      followed by DNA sequencing. Mutations were found in 18/34 (53%) lip and 22/60
      (38%) intra-oral carcinomas. The p53 mutational spectrum of the intra-oral
      carcinomas comprised transitions and transversions in nearly equal frequency (11
      to 10). In comparison, transitions were 3.5 times more frequent than
      transversions (14 to 4) in carcinomas of the lip. The predominant types of base
      change found in intra-oral tumors were G:C-to-T:A transversions and G:C-to-A:T
      transitions (32% each), while in lip tumors G:C-to-A:T transitions (70%) were the
      most frequent. The rate of lip tumors with mutations was higher in non-smokers
      (8/13) than in smokers (9/20). In contrast, p53 mutations in intra-oral tumors
      clustered in smokers (18/47 vs. 2/10). G:C-to-T:A transversions, regarded as
      tobacco smoke-associated in lung cancer, were found in 2 moderate and 4 heavy
      smokers with intra-oral cancer. This base substitution was found in none of our
      lip cancers. In lip tumors, a high rate of mutations occurred at dipyridine sites
      (13/18); among these were 8 C-to-T transitions and 1 CC-to-TT tandem base
      transition. These changes are characteristic of DNA damage caused by UV light.
      The presence of mutational events at the DNA-binding surface of the p53 protein
      may correlate with poor clinical outcome. However, we could not find any
      statistically significant correlations between p53 status and survival. Only the
      recurrence-free interval was significantly shortened in cases with mutations
      affecting residues of the DNA-binding surface of the p53 protein.

PMID- 10962442
TI  - Analysis of the DMBT1 gene in carcinomas of the respiratory tract.
AB  - Loss of chromosome 10q is a critical step during the progression and metastasis
      formation of lung cancer. We recently defined 3 distinct regions of allelic
      imbalances and considered the DMBT1 gene at 10q25-q26 an interesting candidate
      for the most telomeric region. Therefore, we investigated DMBT1 in 25 cancer cell
      lines and 39 primary tumors of the respiratory tract. The analysis by RT-PCR and
      Northern blot hybridization revealed that the gene is expressed in all tumors and
      cell lines and diminished in the SCLC line H187, indicating that RT-PCR is
      critical when used as the single method for the evaluation of gene expression. No
      mutations were found by SSCP analysis of the cDNA and the partially known genomic
      sequence. Similarly, Southern blot hybridization was unable to detect homozygous
      deletions. Allelotyping of the markers D10S587, D10S1708 and D10S1723 located
      near or within the DMBT1 gene did not reach the peak incidence of the 3 minimally
      deleted regions that we recently defined. In summary, our data do not confirm
      previous findings reporting frequent loss of DMBT1 expression in lung cancer.
      However, they strengthen the notion that the responsible gene on chromosome 10q25
      q26 mediating tumor progression and metastasis formation in respiratory tract
      cancer remains enigmatic.

PMID- 10962444
TI  - Familial cancer risks to offspring from mothers with 2 primary breast cancers:
      leads to cancer syndromes.
AB  - The nationwide Swedish Family-Cancer Database was used to analyse the risk of
      cancer among the offspring of bilateral breast cancer patients. We studied 4,734
      such mothers who had 9,391 offspring, of whom 328 presented with a primary cancer
      in the years 1958-1996. Standardised incidence ratios (SIRs) were increased for
      breast [SIR 3.05, 95% confidence interval (CI) 2.57-3.59], ovarian (SIR 1.84, 95%
      CI 1.03-3.05) and anogenital (SIR 1.75, 95% CI 1.11-2.63) cancers and childhood
      sarcomas (SIR 9.39, 95% CI 1.93-29.13). Additionally, squamous-cell skin cancer
      was increased among sons and all childhood cancers among daughters. When analysed
      by histological type, adenocarcinomas of the breast and ovary, all squamous-cell
      carcinomas and tumours at glandular epithelium (seminomas and intestinal
      carcinoids) were increased. Mothers with bilateral breast cancer had an excess of
      2 or more children with cancer. The increased risk of ovarian cancer is
      consistent with germline mutations in the BRCA1 and BRCA2 genes, while the risk
      of soft tissue and bone sarcomas may reflect the association of these tumours
      with Li-Fraumeni syndrome. The increases in squamous-cell carcinomas at many
      sites may reflect a new susceptibility syndrome.

PMID- 10962445
TI  - Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes in women with
      cervical neoplasia.
AB  - Infection with oncogenic human papillomavirus (HPV) types is associated with the
      development of cervical neoplasia (CIN). The E6 and E7 oncoproteins are
      constitutively expressed in these lesions and are therefore putative targets for
      the immune response against HPV. The relation between HPV 16-specific memory
      cytotoxic T-cell precursor (mCTLp) activity to both oncoproteins and the natural
      course of cervical dysplasia was analyzed in 38 patients participating in a
      nonintervention cohort study of women with CIN and 11 HPV 16-positive cervical
      carcinoma patients. In a cross-sectional study at the end of follow-up prior to
      biopsy, 8 of 20 patients with a persistent HPV 16 infection had specific mCTLp
      against at least one of the two oncoproteins. By contrast, no specific mCTLp
      activity was detected in 11 HPV-negative patients or in 7 patients who had
      cleared an HPV 16 infection at the end of follow-up. However, 5 of 11 cervical
      carcinoma patients showed mCTLp activity against the E7 protein only. This study
      demonstrates that HPV 16 oncogene-specific mCTLp are present in women with HPV 16
      positive CIN prior to any intervention. Since HPV-specific mCTLp were detected
      predominantly in women with high-grade lesions or invasive cervical carcinoma and
      not in women who cleared the virus, the role of naturally occurring mCTLp in the
      protection against HPV-associated cervical neoplasia remains to be established.

PMID- 10962446
TI  - Ectopic expression of human topoisomerase IIalpha fragments and etoposide
      resistance in mammalian cells.
AB  - Cellular resistance to etoposide has been correlated both with reduced levels and
      an aberrant cytoplasmic accumulation of the drug's target, topoisomerase IIalpha
      (topo IIalpha). It is not known, however, whether a cytoplasmic pool of topo
      IIalpha is sufficient to confer drug resistance on cultured mammalian cells. In
      our study, we have transfected mouse fibroblasts and human 293 cells with
      truncated forms of human topo IIalpha fused to GFP and have examined the
      transformants for the subcellular localization of topo IIalpha and their
      resistance to etoposide. Transient transfection resulted in high-level expression
      of all GFP-topo IIalpha fusions tested, whereas in stably transfected cells the
      levels varied significantly. Transfectants expressing a central or a carboxy
      terminal topo IIalpha domain (aa 428-1504, 639-1028 or 1028-1504) accumulated
      high levels of the fusion proteins, while only very low amounts of GFP-topo
      IIalpha proteins were observed in cell lines expressing constructs that retain
      the amino-terminus of the enzyme (aa 1-1214, aa 1-939, aa 1-611). Our results
      suggest that the topo IIalpha amino-terminus affects the stability of truncated
      forms of the enzyme in mammalian cells, perhaps due to targeted degradation.
      Assays that screen for cell vitality and DNA synthesis reveal no significant
      changes in etoposide sensitivity in transfected cells expressing high levels of
      cytoplasmic or nuclear localized topo II fusion proteins. Retroviral expression
      of a cytoplasmically anchored domain of human topo IIalpha also failed to confer
      drug resistance. These results suggest that a cytoplasmic pool of topo IIalpha is
      not sufficient to render cultured mammalian cells drug resistant.

PMID- 10962447
TI  - Targeting of a hydrophilic photosensitizer by use of internalizing monoclonal
      antibodies: A new possibility for use in photodynamic therapy.
AB  - Coupling of photosensitizers to tumor-selective monoclonal antibodies (MAbs) is
      an attractive option for improving the selectivity of photodynamic therapy (PDT).
      For this purpose, hydrophilic sensitizers would be most suitable because of their
      solubility in water. However, such sensitizers are known to be ineffective in
      PDT, probably because they cannot readily pass the cell membrane and reach the
      critical intracellular target. We used the model compound TrisMPyP-PhiCO(2)H, a
      hydrophilic porphyrin derivative, to test the hypothesis that hydrophilic
      photosensitizers might become of therapeutic value when directed into the tumor
      cell by use of internalizing MAbs. TrisMPyP-PhiCO(2)H was conjugated using a
      labile ester. Conjugates showed no impairment of integrity on SDS-PAGE, full
      stability in serum in vitro, and optimal immunoreactivity when the sensitizer:MAb
      ratio was </=3. At higher molar ratios, the solubility of the conjugates
      decreased. In vitro internalization experiments showed that TrisMPyP-PhiCONH
      (125)I-cMAb U36 and TrisMPyPPhiCONH-(125)I-mMAb 425 conjugates were internalized
      by A431 cells, in contrast to TrisMPyP-PhiCONH-(125)I-mMAb E48 conjugates. Data
      on the in vitro efficacy of PDT with MAb-conjugated TrisMPyP-PhiCO(2)H showed
      that the internalizing cMAb U36 and mMAb 425 conjugates were phototoxic to A431
      cells, while the non-internalizing E48 conjugate and the unconjugated sensitizer
      were not. Biodistribution data of conjugates with sensitizer:(125)I-cMAb U36
      ratios varying from 1:1 to 3:1 in tumor-bearing nude mice revealed selective
      accumulation in the tumor. Conjugates with higher molar ratios were cleared more
      rapidly from the blood than the unconjugated (125)I-cMAb U36, resulting in lower
      tumor uptake but similar tumor-to-blood ratios. Our data suggest that hydrophilic
      photosensitizers might have therapeutic value when targeted to tumors by
      internalizing MAbs.

PMID- 10962448
TI  - An entirely humanized CD3 zeta-chain signaling receptor that directs peripheral
      blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells.
AB  - Recombinant T-cell receptors with antibody-like specificity for tumor-associated
      antigens are successfully used to direct the cytolytic activity of T cells toward
      tumor cells. Clinical application, however, needs to comply with the low
      immunogenicity of the recombinant receptor, efficient gene transfer into
      peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we
      address these issues and describe an entirely humanized immune receptor for use
      in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a
      single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen
      (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and
      intracellular CD3 zeta signaling chain. To express the receptor in peripheral
      blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned
      out to be equally efficient, with transduction efficiencies of about 5% to 40%,
      depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be
      2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody
      directed to the extracellular IgG domain of the receptor. Upon co-culture with
      CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently
      activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility
      for the adoptive immunotherapy of CEA(+) carcinomas.

PMID- 10962449
TI  - Cycloprodigiosin hydrochloride, H(+)/CL(-) symporter, induces apoptosis and
      differentiation in HL-60 cells.
AB  - Cycloprodigiosin hydrochloride (cPrG * HCl), a novel H(+)/Cl(-) symporter,
      induces acidification of the cytosol and leads to apoptosis in rat and human
      liver cancer cells. In the present study, the effect of cPrG * HCl on a
      promyelocytic leukemia cell line (HL-60) was examined. cPrG * HCl lowered
      intracellular pH and induced apoptosis through up-regulation of Fas ligand,
      activation of stress-activated protein kinase (SAPK/JNK) and caspase. Apoptosis
      induced by cPrG * HCl was strongly suppressed when a cell-permeable weak base,
      imidazole, was present, indicating that cytosol acidification introduced by cPrG
      * HCl triggered caspase activation, leading to apoptosis. Concomitantly, cell
      differentiation into monocyte was also induced by cPrG * HCl both morphologically
      and functionally. However, the cPrG * HCl-induced differentiation was not
      suppressed by addition of imidazole, indicating that the differentiation process
      is unrelated to cytosol acidification. Further, the differentiation induced by
      cPrG * HCl was blocked by tyrosine kinase inhibitors (lavendustin A and HMA) but
      unaffected by the inhibitors of A-kinase (H-89) or C-kinase (H-7). Taken
      together, these findings suggest that cPrG * HCl, through apoptosis and
      differentiation induction, may be useful in leukemia treatment.

PMID- 10962450
TI  - Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian
      population.
AB  - Although tobacco habits have been associated with the risk of oral leukoplakia,
      alcohol drinking and body mass index (BMI) as risk factors have not been well
      established. The purpose of this study is to evaluate the independent effects of
      drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A
      case-control study was conducted, with data from an ongoing randomized oral
      cancer screening trial in Kerala, India. Trained health workers conducted
      interviews and performed oral visual inspections to identify oral premalignant
      lesions such as leukoplakia. The logistic regression model in SAS was used to
      estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927
      leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol
      drinking was a significant risk factor for oral leukoplakia among nonsmokers
      (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after
      adjusting for age, sex, education, BMI and tobacco habits. The association with
      alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men
      (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed
      between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco
      chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for
      men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men
      (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion,
      alcohol drinking was found to be an independent risk factor while BMI might be
      inversely associated with the risk of oral leukoplakia in an Indian population.

PMID- 10962451
TI  - Effect of retinoic acid and palm oil carotenoids on oestrone sulphatase and
      oestradiol-17beta hydroxysteroid dehydrogenase activities in MCF-7 and MDA-MB-231
      breast cancer cell lines.
AB  - Oestrogen is important in the development of breast cancer. Oestrogen receptor
      positive breast cancers are associated with a better prognosis than oestrogen
      receptor negative breast cancers since they are more responsive to hormonal
      treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the
      breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes
      oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH).
      Retinoic acid and carotenoids have been shown to have chemopreventive activity
      against some cancers. The aim of our study was to determine and compare the
      effects of retinoic acid and palm oil carotenoids on growth of and oestrone
      sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and
      oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid
      and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell
      growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase
      activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7)
      M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic
      acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to
      E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2)
      to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2)
      conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase
      activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase
      and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line.
      In conclusion, retinoic acid and carotenoids may prevent the development of
      hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell
      line.

PMID- 10962452
TI  - Lung cancer and environmental tobacco smoke in a non-industrial area of China.
AB  - We report results from a population-based case-control study of lung cancer and
      environmental tobacco smoke (ETS) among never-smokers conducted in 2 rural
      prefectures of China, including 200 female and 33 male lung cancer cases, and 407
      female and 114 male controls, matched on age, sex and prefecture of current
      residence. The odds ratio (OR) for ever-exposed to ETS was 1.19 (95% CI 0.7-2.0),
      with a significant trend (p<0.05) with increasing exposure. ORs were 1.00, 1.04,
      1.13 and 1.51 for non-exposed, <10, 10-19 and >/=20 pack-years of ETS exposure,
      respectively. Excess risks were limited to ETS exposures in childhood (</=18
      years of age). The OR for ever-exposed to ETS in childhood, adjusting for ETS
      exposure in adulthood, was 1. 52 (95% CI 1.1-2.2), with a significant trend
      (p<0.01) with increasing pack-years of childhood exposure, 1.00, 1.43, 1.81 and
      2. 95, respectively. After adjustment for ETS in childhood, there was no excess
      risk from adult ETS exposure. The OR for ever-exposed to ETS in adulthood was
      0.90 (95% CI 0.-1.4). These results were not affected by adjustment for type of
      residential dwelling, type or amount of fuel used, perceived indoor smokiness, or
      measures of socioeconomic status, or omitting next-of-kin respondents.

PMID- 10962453
TI  - Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by
      mandarin juices rich in beta-cryptoxanthin and hesperidin.
AB  - We have reported protective effects of dietary administration of a powder "CHRP"
      containing high amounts of beta-cryptoxanthin and hesperidin prepared from a
      Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat
      aberrant crypt foci through suppression of crypt cell proliferation and/or
      induction of detoxifying enzymes. In the present study, we investigated the
      modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice
      (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta
      cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced
      by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20
      mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or
      MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last
      dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of
      69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5
      administration significantly reduced the frequency of colonic carcinoma [MJ: 35%
      (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15%
      (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47%
      reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5:
      0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells
      positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic
      tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or
      MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These
      findings might suggest effective chemopreventive ability of MJs, especially MJ5,
      in colon tumorigenesis.

PMID- 10962454
TI  - Can we screen high-risk individuals to detect early pancreatic carcinoma?

PMID- 10962455
TI  - Genetic alterations of sporadic colorectal cancer with microsatellite
      instability, especially characteristics of primary multiple colorectal cancers.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to elucidate genetic
      alterations of sporadic colorectal cancers with Microsatellite instability (MSI).
      METHODS: One hundred and ten patients with sporadic colorectal cancer were
      examined. The MSI was assessed using eight microsatellite markers. In addition,
      mutation analysis was performed for Transforming growth-beta type II receptor
      (TGF beta R II), bcl-2 associated X protein (BAX), Insulin-like growth factor II
      receptor (IGF II R), human MutS homolog 3 (hMSH3), human MutS homolog 6 (hMSH6),
      human MutS homolog 2 (hMSH2), and human MutL homolog 1 (hMLH1) genes. Tumors with
      three or more positive loci have been determined to be MSI-H (high-frequency
      MSI), tumors with one or two positive loci were designated as MSI-L (low
      frequency MSI) and tumors lacking apparent instability were designated as MSS
      (microsatellite stable). RESULTS: There were 11 cases with MSI-H (MSI-H group)
      and 99 cases with MSI-L/MSS (MSI-L/MSS group). The frequency of cases with
      multiple colorectal cancer in the MSI-H group was significantly higher than that
      of MSI-L and MSS group (81.8% vs. 34.3%, p = 0.0022). The frequency of cases with
      multiple cancers increased as the number of locus with microsatellite instability
      increased. Among 11 tumors with MSI-H, 7 indicated mutation of the TGF beta R II
      (63.6%), whereas no tumor had a mutation of the TGF beta R II among 20 tumors
      with MSI-L (p = 0.0001). Regarding the BAX, hMSH3, hMSH6 gene, the same trend was
      obtained as the TGF beta R II gene (18.2% vs. 0%, p = 0.0487, 36.4% vs. 0%, p =
      0.0039, 27.3% vs. 0%, p = 0.0140, respectively). Only two cases indicated a
      somatic point mutation of the hMSH2 gene. CONCLUSIONS: The multiple occurrence of
      the colorectal carcinoma may be related to MSI-H as well as the mutation of genes
      possessing repetitive mononucleotide tracts. Furthermore, we recommend strict
      follow-up in sporadic colorectal patients that indicate MSI-H.

PMID- 10962456
TI  - Primary colonic lymphoma.
AB  - BACKGROUND AND OBJECTIVES: The colon is a rare location for gastrointestinal non
      Hodgkin's lymphoma (NHL). This study was undertaken to identify risk factors,
      presentation, treatment, and prognosis for primary colonic lymphoma (PCL) through
      review of a large tertiary care hospital system experience. METHODS: A
      retrospective review of all patients with colonic malignancy and NHL was
      performed using pathology and cancer registry databases from January 1989 to
      December 1998. Criteria for inclusion were no evidence of extraperitoneal
      disease, no leukemic or lymphomatous abnormalities in the blood, and disease
      confined to the colon. RESULTS: Seven patients met the inclusion criteria (4
      male, 3 female; 33-72 years). They represented 1.4% of all NHL, 14% of
      gastrointestinal NHL and 0.9% of all colonic malignancies diagnosed during this
      period. Three of the patients had positive serology for human immunodeficiency
      virus; one was taking steroids chronically for Addison disease. The most common
      presentation was nonspecific abdominal pain. The lack of specific symptoms
      delayed diagnosis from 1-12 months. All patients underwent laparotomy with
      resection. The most common tumor location was the cecum (5/7, 71%). Regional
      lymph nodes were affected in all but 1 patient. All tumors were B-cell lymphomas
      (5 small noncleaved cell, 2 large cell). Six of 7 patients received adjuvant
      chemotherapy. Of the 6 patients available for follow-up four remain alive (12,
      19, 23, and 25 months after diagnosis). In both patients who died the disease
      recurred diffusely. CONCLUSIONS: The colon is a rare location for NHL.
      Immunosuppression is the most common risk factor. Patients' frequently present
      with non-specific abdominal pain, this leads to lengthy delays in diagnosis. Most
      of these tumors are located in the cecal area. Surgery is the most widely
      utilized form of therapy. Although adjuvant therapy is frequently utilized, its'
      impact on survival is unclear.

PMID- 10962457
TI  - The incidence of positive margins with breast conserving therapy following
      mammotome biopsy for microcalcification.
AB  - BACKGROUND AND OBJECTIVES: The ability to achieve clean margins with breast
      conserving therapy varies greatly even when the diagnosis of carcinoma is known
      beforehand. Although several reports reveal that the incidence of positive
      margins decreases after stereotaxic core biopsy of nonpalpable lesions and fine
      needle aspiration biopsy of palpable lesions, the data on the results following
      mammotome biopsy (mmbx) is scanty. METHODS: Two hundred and ninety-eight biopsy
      specimens for mammographically indeterminate microcalcification from 1/97 through
      3/30/98 were reviewed. Biopsies were performed using the biopsys method utilizing
      an 11-gauge multidirectional, vacuum-directed device. RESULTS: Ten percent (n =
      31) of the mammotome biopsies were atypical and 9% (n = 27) were malignant. These
      58 cases (19%) were recommended for surgical excision. The incidence of positive
      margins in this subset was determined. Of patients who underwent lumpectomy as
      their initial surgical procedure 69% had negative surgical margins. Seventy-seven
      percent of patients with carcinoma diagnosed by mammotome biopsy had definitive
      initial surgery with a single surgical procedure. CONCLUSIONS: Mmbx facilitates
      fewer surgical procedures to achieve negative margins, and thus provides a better
      cosmetic result.

PMID- 10962458
TI  - Prognostic significance of young age in breast cancer.
AB  - BACKGROUND: Breast carcinoma is relatively uncommon in younger women and whether
      or not young age at diagnosis is an adverse prognostic factor in this disease has
      been controversial. Our aim in this report is to determine whether the
      histopathologic features and outcome in young and old are different, and whether
      age is a prognostic factor for relapse. METHODS: A retrospective study of
      consecutive 281 stage I or II breast carcinoma patients who had modified radical
      mastectomy was carried out. The patients with a median follow-up period of 45
      months were divided two groups according to their ages. The histopathological
      features and survival of Group 1 and Group 2 were compared with each other.
      Univariate and multivariate prognostic factor analysis for relapse were carried
      out. RESULTS: The patients in Group 1 (younger than 35 years of age) had the
      worst histopathological features related to the prognosis than those in Group 2
      and the difference between the two groups was statistically significant. Whereas
      the rates of 5-year overall survival were 65% in Group 1 and 98% in Group 2 (P <
      0.05), the rates of 5-year relapse-free survival were 40% and 80%, respectively
      (P < 0.05). In univariate analysis of all patients, pathologic tumour size,
      pathologic axillary status, number of metastatic lymph nodes, pathologic stage,
      age, lymphatic vascular invasion were statistically significant factors
      associated with relapse. Multivariate analysis demonstrated that number of
      metastatic nodes (risk ratio RR:4.3 in more than three nodes) and age (RR:3.6 in
      Group 1) were the most important independent prognostic factors for relapse. In
      the patients without axillary involvement, both of univariate and multivariate
      analysis revealed that pathologic tumour size (RR:5.1 in pT(2)) and age (RR:4 in
      Group 1) were the independent prognosticators for relapse. CONCLUSIONS: Young
      patients with breast cancer had the worst histopathological features and the
      worst survival than their older counterparts. Age was an independent significant
      prognostic factor for relapse.

PMID- 10962459
TI  - When not to give radiation therapy after breast conservation surgery for breast
      cancer.
AB  - BACKGROUND AND OBJECTIVES: A significant proportion of breast cancer patients
      treated with breast conservation surgery do not receive adjuvant radiation
      therapy because of advanced age, severe intercurrent disease, or their own
      preference. We studied patients for whom adjuvant radiation was not performed, to
      determine whether the rate of local recurrence was acceptable in particular
      clinical circumstances. METHODS: Patients who had undergone breast conservation
      surgery for breast cancer were identified. The charts of patients who did not
      receive adjuvant radiation therapy were reviewed to identify the reason for
      omitting radiation. Local and distant recurrence rates were examined in relation
      to radiation and reason for omitting radiation. RESULTS: Forty-three (9%, two
      bilateral) of the 487 patients did not receive radiation; 9 because of advanced
      age, 8 refused, 7 had severe intercurrent diseases, 6 developed stage IV disease
      while getting chemotherapy for stage III disease, 5 patients (1 bilateral) had
      two reasons for omission (3 cases: age + intercurrent disease; 2 cases: age +
      stage IV disease; and 1 case: age + small focus of ductal carcinoma in situ) and
      the remainder for miscellaneous reasons. None of the 13 patients with
      intercurrent disease or progression to stage IV disease developed local
      recurrence in their life time; 5 (63%) of 8 patients who refused radiation
      recurred in the breast; 2 (22%) 9 of the elderly patients developed local
      recurrences and none of the 6 cases with more than one reason for omission
      developed local recurrences. CONCLUSIONS: Omission of radiation therapy after
      breast conservation is appropriate for patients with intercurrent diseases, for
      those who develop metastases while receiving preoperative chemotherapy and for
      selected elderly patients. Patients who refuse recommended adjuvant radiation
      therapy have unacceptably high rates of local recurrence. Omission of radiation
      for advanced age alone is associated with local recurrence rates comparable to
      those for younger patients.

PMID- 10962460
TI  - Giant cellular blue nevus of the anterior chest wall mimicking metastatic
      melanoma to the breast: a case report.
AB  - BACKGROUND AND OBJECTIVES: Blue nevi are benign pigmented dermal lesions that can
      mimic cutaneous melanoma in appearance. Cellular components may infiltrate
      subcutaneous tissue. We present a complex case of cellular blue nevus (CBN) to
      demonstrate the ambiguous clinical appearance of these lesions and to provide an
      approach for management of such cases. METHODS: We report an extraordinary case
      of CBN mimicking metastatic melanoma to the breast. A 53-year-old female with an
      acquired giant blue nevus of the chest wall was found to have two new breast
      nodules suspicious for malignancy on routine mammography. These were biopsied and
      interpreted as consistent with metastatic melanoma vs. CBN. The patient underwent
      complete excision of the chest wall nevus and modified radical mastectomy.
      RESULTS: Pathologic evaluation of the chest wall specimen revealed numerous
      collections of deeply pigmented melanocytes scattered throughout the breast
      parenchyma and embracing ductal structures. No mitoses or nuclear polymorphism
      were seen. The diagnosis of CBN involving the chest, breast tissue and axillary
      lymph nodes was made. CONCLUSION: Giant blue nevi overlying the breast can
      develop cellular components that infiltrate subcutaneous and breast tissue
      resulting in the appearance of breast nodules on mammography. A generous excision
      biopsy inclusive of the overlying nevus and breast component may be required to
      establish the dignity of the lesion.

PMID- 10962461
TI  - Assessment of cervical lymph node metastasis in the staging of thoracic
      esophageal carcinoma.
AB  - BACKGROUND: Cervical lymph node metastases (CLM) from esophageal carcinoma are
      regarded as a part of the M component of the TNM classification. Patients with
      CLM, however, can experience extended survival after cervical lymph node
      dissection, unlike patients with other M components. METHODS: Among 844 patients
      with thoracic esophageal carcinoma, 197 underwent esophagectomy with three-field
      dissection of the cervical, mediastinal, and abdominal lymph nodes (3FD). The
      survival of patients with CLM was compared with that of patients with
      hematogenous metastasis (HM), and the prognostic value of CLM was assessed.
      RESULTS: The survival curve for patients with CLM was significantly better than
      that for patients with HM (P = 0. 002). Among the 197 patients who underwent 3FD,
      46 (23.4%) had histologic CLM. Of the 165 patients without hematogenous
      metastases, 22 (13.3%) had histologic CLM. The survival curve for the patients
      with histologic CLM was not significantly differ from that for patients with
      mediastinal or abdominal lymph node metastasis (P = 0. 127, P = 0.155) by
      univariate analyses. CONCLUSIONS: The significantly better survival of patients
      with CLM compared with that of patients with HM strongly suggests that CLM
      carries a prognosis different from the other M components in the staging of
      thoracic esophageal carcinoma. Because the survival curve for patients after 3FD
      was similar to that of patients with metastasis in the mediastinum or abdomen, we
      feel CLM should be included in the N component.

PMID- 10962462
TI  - Paragangliomas-- a decade of clinical experience.
AB  - BACKGROUND AND OBJECTIVES: This study is a review of 14 patients with
      paragangliomas between 1986 and 1996. The purpose was to determine the sites of
      origin, clinical manifestations and analyze the benefits of different treatment
      modalities. METHODS: There were 20 tumors in 14 patients. Three (21.0%) of the
      patients had familial history. There were 7 (50%) females and 7 (50%) males.
      Anatomically 14 (70%) tumors were in head and neck, 5 (25%) were in the
      retroperitoneum, one (5%) was in the heart. Of the head and neck tumors 9
      (64.25%) were in the carotid body, 3 (21.42%) were found in the vagus, and
      2(14.33%) were found in the middle ear. The tumor found in the heart was in the
      atrial septum. The clinical behavior of paragangliomas is determined by cellular
      characteristics, secreting capabilities and tumor location. The symptoms and
      signs depend on the site of origin and the stage at which it presents. The
      clinically functioning tumors were 3 (17%) in our experience and they typically
      present with uncontrolled hypertension. The carotid body and mediastinal tumors
      usually manifested as asymptomatic masses. The intravagal tumors presented with
      paresis of the nerve. Malignancy rarely occurs and is defined by the existence of
      metastasis rather than by histology. In our series 2 (10%) of the patients
      presented with metastasis to lymph nodes, and the vertebrae. The diagnoses in our
      patients were established by CT and MRI scanning. Angiography was performed in 5
      patients with carotid body tumor, two of whom underwent therapeutic embolization
      to reduce the tumor size. The mainstay of treatment was surgical removal, though
      radiation has been advocated for patients who cannot undergo surgery. RESULTS:
      All patients underwent successful surgical resection of the tumor after
      appropriate preoperative preparation. Late mortality occurred in two (12.5%)
      patients at 3 and 5 years from unrelated etiology. Four (25%) patients were lost
      to follow-up. Three (18.7%) patients developed new primaries, two of them at two
      years and one after 8 years. One (6%) patient developed recurrent paraganglioma
      after remaining disease free for 20 years. CONCLUSION: In conclusion,
      paragangliomas are rare with multicentricity being more common in patients with
      familial history. The malignant potential of the tumor is determined by
      metastasis as there are no characteristic cellular change. Aggressive surgery is
      mandatory to obtain disease free survival with low morbidity and mortality.
      Recurrences can also be successfully operated with low morbidity.

PMID- 10962464
TI  - Commentary.

PMID- 10962463
TI  - Fibromatoses of the extremities: clinicopathologic study of 36 cases.
AB  - BACKGROUND AND OBJECTIVES: Fibromatoses of the extremities are rare and often
      recalcitrant to treatment. We evaluated the clinical and pathologic features of a
      group of extremity fibromatoses treated by surgical excision with or without
      adjuvant therapy to determine if any clinical or pathologic parameters were
      predictive of clinical outcome. METHODS: Thirty-six extremity fibromatoses were
      evaluated. A number of clinical and histologic features were correlated with risk
      of local recurrence. RESULTS: The cohort included 19 females and 17 males with
      ages ranging from 11-72 years (mean: 35 years), with 12 tumors of the upper and
      24 tumors of the lower extremity. Tumors ranged in size from 1.5-15.5 cm (mean:
      7.5 cm).Histologically, 26 were infiltrative, 3 had pushing borders and 7 had
      both. Mitotic counts ranged from 0-5/50 high-power fields (mean: 0.74). Surgical
      margins were positive in 22 cases. Seventeen patients were treated with
      postoperative adjuvant therapy including radiation therapy and tamoxifen. Follow
      up information was available in 34 cases (from 1-202 months; mean: 83 months).
      Nineteen patients (56%) had recurrences, including 11 with multiple recurrences
      (range to first recurrence: 5-61 months; mean 23 months). Seventy-one percent of
      patients with a positive surgical margin and clinical follow-up had a local
      recurrence, compared to 31%with a negative surgical margin (P < 0.05). None of
      the other clinical or histologic parameters correlated with the risk for local
      recurrence. CONCLUSIONS: Local control in fibromatoses of the extremities remains
      problematic. Aside from positive surgical margins, none of the other clinical or
      histologic parameters evaluated in this study were useful in predicting the risk
      of local recurrence.

PMID- 10962465
TI  - Villoglandular papillary adenocarcinoma of the cervix: case report.
AB  - The incidence of cervical adenocarcinoma is on the rise over the last several
      decades. It generally carries a worse prognosis than squamous carcinoma.
      Villoglandular papillary adenocarcinoma (VGA) of the cervix has been identified
      as a distinct subset of cervical adenocarcinoma that occurs in young women and
      supposedly carries an excellent prognosis. We report a case of adenocarcinoma of
      the cervix in a young woman that had classical histological features of VGA but
      at operation showed presence of tumor cells in the peritoneal wash. A review of
      world literature on the 56 cases reported so far is presented where occasional
      cases showing disease spread have been reported, suggesting caution in the
      management and follow-up of this clinicopathologic entity.

PMID- 10962466
TI  - Repair of paracolostomal hernias by an extraperitoneal simple technique.

PMID- 10962467
TI  - In vitro bleeding time test can diagnose thrombotic thrombocytopenia purpura and
      can possibly monitor therapeutic plasma apheresis.
AB  - Thrombotic thrombocytopenia purpura (TTP) is perplexing, mainly because of its
      difficult diagnosis and dramatic clinical presentations, high mortality rates,
      and the effectiveness of empirical plasma infusions and plasma exchanges.
      Scientific evidence supports the hypothesis that TTP results from platelet
      hyperagglutination. To support this, a new in vitro bleeding time (Platelet
      Stattrade mark) test was used. Eleven patients had a mean in vitro bleeding time
      of 7.3 +/- 2.1 seconds prior to plasma exchange and eight patients had a mean of
      13.6 +/- 4.7 seconds after the plasma exchange procedure. Normal controls were 14
      +/- 2 seconds. The test was used to monitor plasma exchanges in two patients. At
      the time the platelet count and LDH returned to normal, the Platelet-Stattrade
      mark remained shortened. The two patients relapsed and required continued plasma
      exchanges until Platelet-Stattrade mark corrected to normal. These results
      suggest that plasma exchanges may be effectively monitored by Platelet-Stattrade
      mark rather than the traditional parameters, i.e., LDH. Therefore, the Platelet
      Stattrade mark test may be a useful test to diagnose TTP and monitor therapy in
      this disease.

PMID- 10962468
TI  - Study of three patients with thrombotic thrombocytopenic purpura exchanged with
      solvent/detergent-treated plasma: is its decreased protein S activity clinically
      related to their development of deep venous thromboses?
AB  - Solvent/detergent treated plasma (S/DP) has reduced protein S activity (about 0.5
      units/mL) as compared with fresh frozen plasma (FFP). When used as replacement
      fluid for repetitive therapeutic plasma exchange (PEX), e.g., in patients with
      thrombotic thrombocytopenic purpura (TTP), S/DP could lead to lowered protein S
      levels and, possibly, risk of hypercoagulable complications. We describe three
      patients with TTP who had low functional protein S (FPS) levels during PEX for
      TTP. Each developed one or more deep vein thromboses (DVTs) while receiving 100%
      S/DP or 50% S/DP and 50% cryosupernatant plasma (CSP) as replacement fluid. FPS
      levels rose when 100% CSP was substituted for S/DP. Our observations suggest that
      use of S/DP alone or in 50% combination with CSP as replacement fluid in PEX for
      TTP may lead to difficulty in maintaining safe FPS levels. Determination of risk
      of resulting clinically significant thrombotic events requires further study.

PMID- 10962469
TI  - Image-guided central venous catheter placement for apheresis in allogeneic stem
      cell donors.
AB  - Peripheral blood stem cell harvest by apheresis is an increasingly important
      procedure utilized in the treatment of many malignancies. Whether autologous or
      allogeneic, it is frequently performed via peripheral access because of concern
      over major complications associated with central venous catheter placement. This
      study was to determine the safety and success, complications and premature
      failure rates for radiolocally placed ultrasound-guided non-tunneled central
      venous catheters placed for apheresis in a donor (allogeneic) population. One
      hundred central venous catheters were placed in ninety-one individuals for
      allogeneic stem cell harvest. Procedural success and complications relating to
      placement were noted in all. In 97 cases the number of needle passes required for
      venous cannulation and whether this was achieved with a single wall puncture was
      noted. Duration of catheterization and reason for removal were recorded in all
      cases. All catheters were placed by a right transjugular route. Venous
      cannulation and functioning line placement was achieved in every case; 92/97
      (95%) required only a single needle pass and 84/97 (87%) only a single wall
      puncture. There were no placement related complications; 94 catheters were
      removed the same day with the remainder removed within 48 hr. All completed
      apheresis. Our study demonstrates the safe use of central venous catheters for
      apheresis in normal donors if ultrasound guidance is used for the puncture and
      the duration of catheterization is short.

PMID- 10962471
TI  - Treatment of antibody-mediated accelerated rejection using plasmapheresis.
AB  - Accelerated antibody-mediated rejection is believed to be due to an anamnestic
      response of an allograft recipient to donor antigens. Few reports have
      demonstrated successful reversal of this type of rejection, and no consensus
      exists for either diagnosis or treatment. Accelerated antibody-mediated rejection
      was suspected on the basis of clinical findings and confirmed by cytotoxic and
      flow crossmatches, and leukocyte antibody screens. Serial crossmatches and
      antibody screens were performed through post-transplant day 112. Plasmapheresis
      was performed on post-transplant days 1, 2, 4, 6, 12, 14, 20, and 28. The
      duration of treatment was determined by the cytotoxic crossmatch results. We
      present a case of successfully treated accelerated antibody-mediated rejection
      using plasmapheresis and aggressive immunosuppression. Serial crossmatch and
      leukocyte antibody screen results are presented that confirm the production of
      anti-donor antibody and demonstrate the effectiveness of the treatment protocol
      in eliminating detectable levels of the anti-donor antibody. At 6 months post
      transplant, the patient has a serum creatinine of 1.1 and has not had any
      additional rejection episodes or infectious complications. The protocol suggested
      in this paper allows for rapid diagnosis, institution of treatment, and
      monitoring the efficacy of treatment, providing the basis for follow-up clinical
      trials.

PMID- 10962473
TI  - Mapping a quantitative trait locus via the EM algorithm and Bayesian
      classification.
AB  - Mapping a locus controlling a quantitative genetic trait (e.g., blood pressure)
      to a specific genomic region is of considerable interest. Data on the
      quantitative trait under consideration and several codominant genetic markers
      with known genomic locations are collected from members of families and
      statistically analyzed to draw inferences on the genomic position of the trait
      locus. The vector of parameters of interest comprises the pairwise recombination
      fractions, theta, between the putative quantitative trait locus and the marker
      loci. One of the major complications in estimating theta for a quantitative trait
      in humans is the lack of haplotype information on members of families. The
      purpose of this study was to devise a computationally simple and efficient method
      of estimation of theta in the absence of haplotype information. We have proposed
      a two-stage estimation procedure using the expectation-maximization (EM)
      algorithm. In the first stage, parameters of the QTL are estimated based on data
      of a sample of unrelated individuals. From estimates thus obtained, we have used
      a Bayes' rule to infer QTL genotypes of parents in families. Finally, in the
      second stage of the procedure, we have proposed an EM algorithm for obtaining the
      maximum likelihood estimate of theta based on data of informative families (which
      are identified upon inferring parental QTL genotypes performed in the first
      stage). We have shown, using simulated data, that the proposed procedure is cost
      effective, computationally simple, and statistically efficient. As expected,
      analysis of data on multiple markers jointly is more efficient than the analysis
      based on single markers.

PMID- 10962470
TI  - Acute thrombotic thrombocytopenic purpura following abdominal surgeries: a report
      of three cases.
AB  - Acute thrombotic thrombocytopenic purpura (TTP) occurred in three patients
      following abdominal surgeries. One patient underwent extensive lysis for
      intestinal adhesions with bowel resection, another cholecystectomy for acute
      cholecystitis, and the third right colectomy and partial intestinal resection for
      colon cancer. The diagnosis of acute TTP was established on the basis of absent
      hematologic features of TTP prior to surgery and development of microangiopathic
      hemolytic anemia (MAHA), thrombocytopenia, and unexplained mental changes after
      surgery. Hematologic evidence of TTP developed 3 to 9 days after surgery. Other
      clinical features were acute respiratory distress syndrome (ARDS) in two patients
      and peripheral digit ischemic syndrome (PDIS) also in two patients. In all three
      patients, establishing the diagnosis of TTP was delayed. Exchange plasmapheresis
      in one patient was ineffective due to associated ARDS and two others died soon
      after the diagnosis was established. In view of our experience, postoperative TTP
      should be considered in the differential diagnosis of the patient who develops
      unexplained anemia and thrombocytopenia following an abdominal surgery. Presence
      of hemolytic anemia, schistocytosis, and unexplained thrombocytopenia should
      alert the possibility of TTP.

PMID- 10962474
TI  - Variance components analysis for pedigree-based censored survival data using
      generalized linear mixed models (GLMMs) and Gibbs sampling in BUGS.
AB  - Complex human diseases are an increasingly important focus of genetic research.
      Many of the determinants of these diseases are unknown and there is often a
      strong residual covariance between relatives even when all known genetic and
      environmental factors have been taken into account. This must be modeled
      correctly whether scientific interest is focused on fixed effects, as in an
      association analysis, or on the covariance structure itself. Analysis is
      straightforward for multivariate normally distributed traits, but difficulties
      arise with other types of trait. Generalized linear mixed models (GLMMs) offer a
      potentially unifying approach to analysis for many classes of phenotype including
      right censored survival times. This includes age-at-onset and age-at-death data
      and a variety of other censored traits. Markov chain Monte Carlo (MCMC) methods,
      including Gibbs sampling, provide a convenient framework within which such GLMMs
      may be fitted. In this paper, we use BUGS ("Bayesian inference using Gibbs
      sampling": a readily available, generic Gibbs sampler) to fit GLMMs for right
      censored survival times in nuclear and extended families. We discuss parameter
      interpretation and statistical inference, and show how to circumvent a number of
      important theoretical and practical problems. Using simulated data, we show that
      model parameters are consistent. We further illustrate our methods using data
      from an ongoing cohort study. Finally, we propose that the random effects
      associated with a genetic component of variance (e.g., sigma(2)(A)) in a GLMM may
      be regarded as an adjusted "phenotype" and used as input to a conventional model
      based or model-free linkage analysis. This provides a simple way to conduct a
      linkage analysis for a trait reflected in a right-censored survival time while
      comprehensively adjusting for observed confounders at the level of the individual
      and latent environmental effects shared across families.

PMID- 10962475
TI  - Familial cancer risks in affected sibships: results from the Swedish family
      cancer database.
AB  - We used the nationwide Swedish Family-Cancer Database to assess familial risks to
      sibs in sibsibs where at least two sibs had concordant cancer and their parents
      either concordant or discordant cancer. Familial relative risks (FRRs) were
      calculated by comparing to concordant sib-pairs whose parents had no cancer.
      Cancer sites were included if at least ten such concordant sib-pairs were found.
      In situ cancers were included in order to increase the numbers of cases.
      Concordant triads, one parent and the sib-pair affected, had an FRR over 100 for
      thyroid (FRR 399), colon, all bowel, and ovarian cancer. In these cancers, some
      40% or more of the concordant sib-pairs belonged to this group. Melanoma and
      cancer of the nervous system showed FRRs of about 20, and invasive breast cancer
      of only 2. 9; in these cancers no more than 10% of the concordant sib-pairs
      belonged to the concordant triads. Discordant family sets, one or two parents
      presenting with a cancer discordant from that of the sib-pair, showed an FRR of
      about 3.0 and breast cancer about 2.0, suggesting the involvement of familial
      effects shared by many forms of cancer.

PMID- 10962476
TI  - Determination of bone mineral density of the hip and spine in human pedigrees by
      genetic and life-style factors.
AB  - In 40 human pedigrees with 563 subjects, we evaluated the contribution of genetic
      and life-style factors (exercise, smoking, and alcohol consumption) and the
      interactions between non-genetic factors in determining bone mineral density
      (BMD) of the hip and spine. In our analysis, we adjusted for age, weight, height,
      menopausal status in females, life-style factors, and the significant
      interactions among these factors. For the spine and hip BMD, heritabilities
      (h(2)) (+/- SE) were, respectively, 0.68 (0.21) and 0.86 (0.28) in males and 0.64
      (0.13) and 0.67 (0.14) in females. Exercise had significant beneficial effects
      for male spine BMD and female hip BMD. Alcohol consumption experienced in our
      sample had significant beneficial effects on hip BMD in both sexes. Although the
      main effect of smoking was not significant, there were significant interaction
      effects between smoking and other important factors (e.g., exercise, weight,
      alcohol consumption). For example, for female spine BMD, exercise had significant
      beneficial effects in smokers; however, its effect in non-smokers was non
      significant. This result indicates that exercise may reduce deleterious effects
      of smoking (if any) on BMD, but may have minor effects in increasing BMD in non
      smokers. The various interaction effects among risk factors explicitly revealed
      here for the first time indicate that the detailed effects and direction of
      individual risk factors may depend on the presence and magnitude of other
      factors. Weight invariably affected BMD of the hip and spine in both sexes. Age
      effects were significant for hip BMD, but not for male spine BMD.

PMID- 10962477
TI  - Twin study of adolescent genetic susceptibility to mosquito bites using ordinal
      and comparative rating data.
AB  - Ordinal and comparative rating measures of mosquito attraction and mosquito bite
      frequency and symptoms were administered in a self-report questionnaire format to
      a sample of 197 monozygotic and 326 dizygotic Australian adolescent twin pairs at
      age 12 between 1992 and 1999, in order to investigate the environmental and
      possibly genetic determinants of variation between individuals. Repeat measures
      were obtained from the twin pairs at age 14. Ordinal variable measures, although
      providing some support for genetic effects on mosquito susceptibility, were
      affected by low repeatability. However, analysis of a comparative rating variable
      "compared with your twin, who is bitten by mosquitoes more often?" indicated a
      strong genetic influence on frequency of being bitten by mosquitoes, with no
      significant differences observed between males and females. Comparative rating
      questionnaire items are a potentially valuable tool for complementing and
      improving the results obtained from more conventional absolute measures.

PMID- 10962478
TI  - Microtubule configurations and post-translational alpha-tubulin modifications
      during mammalian spermatogenesis.
AB  - The mechanisms underlying cell cycle progression and differentiation are tightly
      entwined with changes associated in the structure and composition of the
      cytoskeleton. Mammalian spermatogenesis is a highly intricate process that
      involves differentiation and polarization of the round spermatid. We found that
      pachytene spermatocytes and round spermatids have most of the microtubules
      randomly distributed in a cortical network without any apparent centrosome. The
      Golgi apparatus faces the acrosomal vesicle and some microtubules contact its
      surface. In round spermatids, at step 7, there is an increase in short
      microtubules around and over the nucleus. These microtubules are located between
      the rims of the acrosome and may be the very first sign in the formation of the
      manchette. This new microtubular configuration is correlated with the beginning
      of the migration of the Golgi apparatus from the acrosomal region towards the
      opposite pole of the cell. Next, the cortical microtubules form a bundle running
      around the nucleus perpendicular to the main axis of the cell. At later stages,
      the nuclear microtubules increase in size and a fully formed manchette appears at
      stage 9. On the other hand, acetylated tubulin is present in a few microtubules
      in pachytene spermatocytes and in the axial filament (precursor of the sperm
      tail) in round spermatids. Our results suggest that at step 7, the spermatid
      undergoes a major microtubular reordering that induces or allows organelle
      movement and prepares the cell for the formation of the manchette and further
      nuclear shaping. This new microtubular configuration is associated with an
      increase in short microtubules over the nucleus that may correspond to the
      initial step of the manchette formation. The new structure of the cytoskeleton
      may be associated with major migratory events occurring at this step of
      differentiation.

PMID- 10962479
TI  - Redundancy of lamellipodia in locomoting Walker carcinosarcoma cells.
AB  - Locomoting metazoan cells usually form lamellipodia at the leading front and it
      is widely accepted that lamellipodia are required for locomotion. In this case,
      suppression of lamellipodia must stop locomotion. However, the experiments show
      that lamellipodia are redundant for locomotion of Walker carcinosarcoma cells.
      Low latrunculin A concentrations (10(-7) M) transform polarised locomoting cells
      with lamellipodia into cells without morphologically recognisable protrusions
      showing an increased speed of locomotion and a reduced amount of cellular F
      actin. Whereas untreated cells show a fairly linear distribution of F-actin along
      the plasma membrane, cells lacking morphologically recognizable protrusions at
      the front show modifications at the front consisting in an irregular distribution
      of F-actin with formation of small or large patches of F-actin alternating with
      small or large gaps in the F-actin layer. This is associated with a reduced
      resistance to deformation pressure at the front of the cell. High concentrations
      of latrunculin A (>10(-7) M) compromising contraction at the rear stop
      locomotion, suggesting that cortical contraction is important for locomotion to
      occur in these cells. The results are consistent with the view that actin
      polymerization is important for formation of lamellipodia but they are not
      compatible with the view that lamellipodia are essential for locomotion of Walker
      carcinosarcoma cells. A unifying hypothesis for the formation of different types
      of protrusions is proposed.

PMID- 10962480
TI  - The lens membrane skeleton contains structures preferentially enriched in
      spectrin-actin or tropomodulin-actin complexes.
AB  - The spectrin-based membrane skeleton plays an important role in determining the
      distributions and densities of receptors, ion channels, and pumps, thus
      influencing cell shape and deformability, cell polarity, and adhesion. In the
      paradigmatic human erythrocyte, short tropomodulin-capped actin filaments are
      cross-linked by spectrin into a hexagonal network, yet the extent to which this
      type of actin filament organization is utilized in the membrane skeletons of
      nonerythroid cells is not known. Here, we show that associations of tropomodulin
      and spectrin with actin in bovine lens fiber cells are distinct from that of the
      erythrocyte and imply a very different molecular organization. Mechanical
      disruption of the lens fiber cell membrane skeleton releases tropomodulin and
      actin-containing oligomeric complexes that can be isolated by gel filtration
      column chromatography, sucrose gradient centrifugation and immunoadsorption.
      These tropomodulin-actin complexes do not contain spectrin. Instead, spectrin is
      associated with actin in different complexes that do not contain tropomodulin.
      Immunofluorescence staining of isolated fiber cells further demonstrates that
      tropomodulin does not precisely colocalize with spectrin along the lateral
      membranes of lens fiber cells. Taken together, our data suggest that tropomodulin
      capped actin filaments and spectrin-cross-linked actin filaments are assembled in
      distinct structures in the lens fiber cell membrane skeleton, indicating that it
      is organized quite differently from that of the erythrocyte membrane skeleton.

PMID- 10962481
TI  - Flagellar elongation induced by glucose limitation is preadaptive for Trypanosoma
      cruzi differentiation.
AB  - Trypanosomes must sense and respond to environmental change in order to progress
      through their life cycles. The American trypanosome, Trypanosoma cruzi,
      differentiates from the noninfective epimastigote form to the infective
      metacyclic form spontaneously in axenic culture. Here, we investigate the initial
      stimulus for that change and demonstrate that T. cruzi epimastigotes sense
      limitation of glucose in the medium and respond by undergoing significant
      morphological and biochemical change. As part of this change, the mean flagellar
      length of the population triples, which is correlated with an increased ability
      to maintain interactions with hydrophobic substrates, a requirement for
      differentiation to the next life cycle stage.

PMID- 10962482
TI  - A sensitive screening assay for secreted motility-stimulating factors.
AB  - Secreted motility-stimulating factors are often expressed and secreted at low
      concentrations that are difficult to detect by Northern or Western blot analysis.
      Autotaxin (ATX) is a tumor-secreted autocrine motility-stimulating factor that
      has been associated with tumor invasion and metastatic potential. Although ATX
      has a number of enzymatic activities, it is most sensitively detected by its
      induced chemotactic response. After transfecting ATX cDNA into NIH3T3
      fibroblasts, we developed a motility-based method to screen the resulting cloned
      cells for secretion of active protein. We placed the cloned and transfected cells
      into the bottom wells of a modified Boyden chamber and placed responding cells
      (A2058 human melanoma cells) into the upper wells. After overnight incubation,
      the membrane that separated the two chambers was removed and stained. Simple
      densitometry measurements were sufficiently accurate to determine which clones
      secreted active protein. Utilizing this method, 4 positive cell lines were chosen
      out of 36 tested clones. Further tests on the expanded cell lines determined that
      all 4 were secreting ATX. Thus, this modified Boyden chamber assay appears to
      provide a rapid and highly adaptable means to identify cells that secrete
      motility-stimulating factors.

PMID- 10962483
TI  - Mutant Rac1B expression in Dictyostelium: effects on morphology, growth,
      endocytosis, development, and the actin cytoskeleton.
AB  - Rac1 is a small G-protein in the Ras superfamily that has been implicated in the
      control of cell growth, adhesion, and the actin-based cytoskeleton. To
      investigate the role of Rac1 during motile processes, we have established
      Dictyostelium cell lines that conditionally overexpress epitope-tagged
      Dictyostelium discoideum wild-type Rac1B (DdRac1B) or a mutant DdRac1B protein.
      Expression of endogenous levels of myc- or GFP-tagged wild-type DdRac1B had
      minimal effect on cellular morphologies and behaviors. By contrast, expression of
      a constitutively active mutant (G12-->V or Q61-->L) or a dominant negative mutant
      (T17-->N) generated amoebae with characteristic cellular defects. The
      morphological appearance of actin-containing structures, intracellular levels of
      F-actin, and cellular responses to chemoattractant closely paralleled the amount
      of active DdRac1B, indicating a role in upregulating actin cytoskeletal
      activities. Expression of any of the three mutants inhibited cell growth and
      cytokinesis, and delayed multicellular development, suggesting that DdRac1B plays
      important regulatory role(s) during these processes. No significant effects were
      observed on binding or internalization of latex beads in suspension or on
      intracellular membrane trafficking. Cells expressing DdRac1B-G12V exhibited
      defects in fluid-phase endocytosis and the longest developmental delays; DdRac1B
      Q61L produced the strongest cytokinesis defect; and DdRac1B-T17N generated
      intermediate phenotypes. These conditionally expressed DdRac1B proteins should
      facilitate the identification and characterization of the Rac1 signaling pathway
      in an organism that is amenable to both biochemical and molecular genetic
      manipulations.

PMID- 10962484
TI  - Simultaneous quantitative cassette analysis of drugs and detection of their
      metabolites by high performance liquid chromatography/ion trap mass spectrometry.
AB  - A method using high performance liquid chromatography (HPLC) coupled with ion
      trap mass spectrometry (MS) for simultaneous quantification of multiple drugs and
      detection of their metabolites is described. The new approach offers a
      significant increase in analytical throughput and is illustrated with analysis of
      the in vitro metabolism of 19 alpha-1a receptor antagonists. The compounds were
      separated into four cassette groups by using a computer program as well as by
      manual examination. The samples from incubation with dog liver microsomes were
      pooled into the designed cassette groups and analyzed by HPLC/electrospray (ESI)
      ion trap MS in full-scan mode. The metabolic stability of the drugs was
      determined by comparing their signals after incubation for 0 and 60 min,
      respectively. The quantitative results from the cassette analysis procedure
      agreed well with those obtained from conventional discrete analysis. In addition,
      the technique allowed simultaneous detection of metabolites formed during the
      same incubation without having to reanalyze the samples. The metabolites were
      first characterized by nominal mass measurement of the corresponding protonated
      molecules. Subsequent multi-stage tandem mass spectrometry (MS(n)) on the ion
      trap instrument allowed confirmation of the detected metabolites.

PMID- 10962485
TI  - A new approach for measuring protein adducts from benzo[a]pyrene diolepoxide by
      high performance liquid chromatography/tandem mass spectrometry.
AB  - The long-range goal of the present study is the development of a general approach
      for in vivo dosimetry of reactive metabolites of polycyclic aromatic hydrocarbons
      (PAHs), to be used as a tool in cancer risk assessment. With benzo[a]pyrene (BaP)
      chosen as indicator and a model of PAHs this study aims at the development of a
      method for the determination of adducts to histidine (His) in hemoglobin (Hb) and
      serum albumin (SA) of reactive metabolites of BaP. The predominantly mutagenic
      metabolite of BaP has been shown to be a diolepoxide isomer, +(anti)r-7, t-8
      dihydroxy-t-9,10-epoxy-7,8, 9,10-tetrahydrobenzo[a]pyrene (+BPDE). In comparison
      with other methods for protein degradation, hydrazinolysis was found to be
      sufficiently effective and mild. The His adduct isolated after protein
      hydrazinolysis, with protection by tert-butyloxycarbonyl (Boc) of the hydrazide
      and alpha-amino groups, was shown to be N(im)- +/- (r-7, t-8, t-9-trihydroxy-7,
      8, 9, 10-tetrahydrobenzo[a]pyren-c-10-yl)-N(alpha), N(2)-bis(tert
      butyloxycarbonyl)-L-histidinehydrazide. Isomers of this compound, used as
      references, were synthesized and characterized by liquid chromatography/tandem
      mass spectrometry (LC/MS/MS). Adducts in Hb and SA from in vitro treatment with
      BPDE were characterized after hydrazinolysis by HPLC-UV/MS, muHPLC/MS/MS and gas
      chromatography/mass spectrometry (GC/MS). Approximately 70 and 10% of the
      isolated BPDE adducts from SA and Hb, respectively, were His adducts. Other
      products were released as BaP tetrols and BaP triols. For the purpose of
      enrichment/purification of BPDE-His adducts, C(18) and cation exchange solid
      phase extraction (SPE) were utilized. The sensitivity obtained by this new
      approach, based on hydrazinolysis of protein, enrichment by SPE and analysis with
      muHPLC/MS/MS (APCI), is in the low-fmole range.

PMID- 10962487
TI  - Bioanalytical applications of 'fast chromatography' to high-throughput liquid
      chromatography/tandem mass spectrometric quantitation.
AB  - A fast chromatographic separation approach that enables rapid method development
      for high-throughput sample quantification is discussed. This approach has been
      used to analyze samples from various biological matrices. Data are presented from
      in vivo pharmacokinetic studies (plasma) and in vitro drug metabolism and
      transport studies (hepatic microsomes, hepatocytes, and Caco-2 cells).

PMID- 10962486
TI  - Grazing incidence surface-induced dissociation of protonated peptides generated
      by matrix-assisted laser desorption/ionization.
AB  - The grazing incidence surface-induced dissociation (GI-SID) of various protonated
      peptides with typical kinetic energies of 350 eV was investigated. Peptide ions
      were generated by matrix-assisted laser desorption/ionization (MALDI) using
      delayed extraction. The collision target surfaces used were aluminum and a liquid
      film of perfluorinated hydrocarbons. All peptides studied in these experiments
      showed enhanced fragment ion yields at grazing incidence (GI-SID effect) as
      observed in our former experiments with other precursor ion types. In general the
      GI-SID spectra exhibit N-terminal a(1)-type fragment ions, immonium ions and side
      chain fragment ions in the low mass-to-charge region. Fragment ion series of the
      peptide backbone were not observed, which are typical and abundant in the spectra
      of established fragmentation techniques like collision-induced dissociation,
      MALDI post-source decay or surface-induced dissociation at steeper angles. The
      potential of the GI-SID process to yield useful information for primary structure
      determination of peptides is indicated by the observed differences in the GI-SID
      spectra of the isomeric dipeptides LR and IR.

PMID- 10962488
TI  - Prediction of quadrupole mass filter performance for hyperbolic and circular
      cross section electrodes
AB  - A computer model has been developed that is able to predict the performance of a
      quadrupole mass spectrometer (QMS) for any constant cross section electrode
      geometry. It has been used to predict the performance of QMS systems with both
      hyperbolic and circular cross section electrodes. The predictions confirm the
      limited previous work that indicates QMS performance is poorer when circular
      cross section electrodes are used rather than hyperbolic ones. There is also an
      indication that use of circular electrodes causes a movement of the peak position
      from the expected one and produces an extended tail on the low mass side of the
      peak. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10962489
TI  - Electron impact induced fragmentation of ( p-substituted phenyl)-(4'
      methylphenacyl) sulfones: contribution of sulfinate ester rearrangements
AB  - The molecular ions of the title compounds are usually very unstable. The main
      fragmentation corresponds to the formation of p-MeC(6)H(4)CO(+) as would be
      expected. Another abundant fragment ion was [M - SO(2)](+) which is formed both
      from the original sulfone and from the rearranged sulfinate esters. There are,
      however, three primary ions which can be traced back to each isomeric molecular
      ion: p-RC(6)H(4)SO(2)(+) to the original sulfone, p-RC(6)H(4)SO(+) to
      the.CH(2)S(=O)O-. type sulfinate ester and p-RC(6)H(4)OH(+.) to the.CH(2)OS(=O).
      type sulfinate ester of which the latter seems by far to dominate. Copyright 2000
      John Wiley & Sons, Ltd.

PMID- 10962490
TI  - Comparative quantification and identification of phosphoproteins using stable
      isotope labeling and liquid chromatography/mass spectrometry.
AB  - A new liquid chromatography/mass spectrometry (LC/MS) method is described for
      relative quantification of phosphoproteins to simultaneously compare the
      phosphorylation status of proteins under two different conditions. Quantification
      was achieved by beta-elimination of phosphate from phospho-Ser/Thr followed by
      Micheal addition of ethanethiol and/or ethane-d(5)-thiol selectively at the vinyl
      moiety of dehydroalanine and dehydroamino-2-butyric acid. The method was
      evaluated using the model phosphoprotein alpha(S1)-casein, for which three
      phosphopeptides were found after tryptic digestion. Reproducibility of the
      relative quantification of seven independent replicates was found to be 11% SD.
      The dynamic range covered two orders of magnitude, and quantification was linear
      for mixtures of 0 to 100% alpha(S1)-casein and dephospho-alpha(S1)-casein (R(2) =
      0.986). Additionally, the method allowed protein identification and determination
      of the phosphorylation sites via MS/MS fragmentation.

PMID- 10962491
TI  - Chip-based capillary electrophoresis with an electrodeless nanospray interface.
AB  - A sheathless and electrodeless nanospray interface has been used to interface a
      polycarbonate capillary electrophoresis (CE) chip to a mass spectrometer (MS).
      The chip was made of two flat polycarbonate plates which were bolted together.
      Channels were imprinted in one of the plates with metal wires, using a hydraulic
      press. A short tapered capillary connected to the chip was used as the nanospray
      emitter. The advantage of this electrodeless interface is that it was not
      necessary to apply a electrospray voltage to the chip or the nanospray emitter.
      Instead, the CE voltage already applied to the buffer compartment on the chip, to
      drive the electrophoresis, was used to generate the spray also. A low
      conductivity buffer of 1.25 mmol/L ammonium acetate in 80% methanol was used to
      obtain a large electric field across the buffer channel. The performance of the
      device was evaluated by analyzing a mixture of three beta-agonists Relative
      standard deviation (RSD) values obtained were between 4.8 and 5.0%. A sample
      concentration of 40 nmol/L resulted in a signal-to-noise ratio of 2 to 5 for the
      different components. Compared to a conventional CE analysis in a fused silica
      capillary with UV detection, only a minor loss of resolution was observed, which
      can be attributed to the design of the chip.

PMID- 10962492
TI  - A study of resonance electron capture ionization on a quadrupole tandem mass
      spectrometer.
AB  - Procedures that allow the realization of resonance electron capture (REC) mode on
      a commercial triple-quadrupole mass spectrometer, after some simple
      modifications, are described. REC mass spectrometry (MS) and tandem mass
      spectrometry (MS/MS) experiments were performed and spectra for some compounds
      were recorded. In particular, the charge-remote fragmentation (CRF) spectra of [M
      - H](-) ions of docosanoic and docosenoic acids under low-energy collisionally
      activated dissociation (CAD) conditions were obtained, and showed that there were
      no significant differences for [M - H](-) ions produced at different resonances
      (i.e. for [M - H](-) ions with different structures). This observation was
      explained on the basis of results obtained from deuterium-labeled fatty acids,
      which showed that different CRF ions (but with the same m/z value in the absence
      of labels) could be produced by different mechanisms, and all of them were
      obviously realized under CAD conditions that made spectra practically
      indistinguishable. The other example, which compared the REC-MS/MS spectrum of [M
      - H](-) ions and EI-MS/MS spectrum of M(+.) ions of daidzein, demonstrated the
      potential of the REC-MS/MS technique for more complex structure elucidation.

PMID- 10962493
TI  - In vivo microdialysis and reverse phase ion pair liquid chromatography/tandem
      mass spectrometry for the determination and identification of acetylcholine and
      related compounds in rat brain.
AB  - A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been
      developed for the determination of basal acetylcholine (ACh) in microdialysate
      from the striatum of freely moving rats. A microdialysis probe was surgically
      implanted into the striatum of the rats and Ringer's solution was used as the
      perfusion medium at a flow rate of 2 microL per minute. The samples were then
      analyzed off-line by LC/MS/MS experiments. The separation of ACh and choline (Ch)
      was carried out using reverse phase ion pair liquid chromatography with
      heptafluorobutyric acid as a volatile ion pairing reagent. Analytes were detected
      by electrospray ionization tandem mass spectrometry in the positive ion mode. The
      detection limit for ACh was 1.4 fmol on column, which is at least three times
      lower than previously reported. Three quaternary ammonium compounds in the rat
      brain microdialysate were also identified by tandem mass spectrometry experiments
      in which the unknown mass spectra were compared with standard reference
      compounds. These compounds were identified as carnitine, acetylcarnitine and (3
      carboxypropyl)trimethylammonium. This is the first known report of the compound
      (3-carboxypropyl)trimethylammonium being found in rat brain.

PMID- 10962494
TI  - Matrix-assisted laser desorption/ionization time-of-flight analysis of Bacillus
      spores using a 2.94 microm infrared laser.
AB  - The performance of infrared (2.94 microm) and ultraviolet (337 nm) lasers were
      compared for analysis of purified spores of B. subtilis, B. cereus and B.
      globigii on a four-inch end-cap reflectron time-of-flight instrument. Infrared
      matrix-assisted laser desorption/ionization (IR-MALDI) mass spectra of these
      microorganisms displayed a larger number of biomarker peaks above m/z 4000,
      compared with UV-MALDI. Biomarker peaks were observed at higher m/z values with
      the IR laser.

PMID- 10962495
TI  - Do amines react with protonated peptides in the gas phase via transacylation
      reactions to induce peptide bond cleavage?
AB  - The proposal that protonated peptides react with NH(3) in the gas phase via
      transacylation reactions (Tabet et al., Spectros. Int. J. 5: 253 1987) has been
      investigated by studying the reactions of the fixed charge derivatives
      [RC(O)NMe(2)CH(2)CO(2)H](+) (R=Me and Ph) with pyridine and triethylamine and the
      reactions of protonated glycine oligomers and leucine enkenphalin with
      butylamine. Under the near thermal conditions of the quadrupole ion trap, both
      the fixed charge derivatives as well as the protonated peptides react with the
      amines via either proton transfer or proton bound dimer formation. Collision
      induced dissociation of protonated peptides in the presence of butylamine yields
      b(n) and y(n) sequence ions as well as [b(n) + BuNH(2)](+) and [y(n) +
      BuNH(2)](+) ions. MS(3) experiments reveal that a major route to these [b(n) +
      BuNH(2)](+) and [y(n) + BuNH(2)](+) ions involves ion-molecule reactions between
      the b(n) and y(n) sequence ions and butylamine. MS(4) experiments, carried out to
      determine the nature of the [b(n) + BuNH(2)](+) ions, reveal that they correspond
      to a mixture of hydrogen bonded (i.e. proton bound dimer) and covalent amide bond
      structures.

PMID- 10962496
TI  - Determination of the metabolites of gestrinone in human urine by high performance
      liquid chromatography, liquid chromatography/mass spectrometry and gas
      chromatography/mass spectrometry.
AB  - Gestrinone was studied by high performance liquid chromatography (HPLC) for
      screening and by gas chromatography/mass spectrometry (GC/MS) for confirmation.
      When the chromatograms of blank, spiked urine and dosed urine were compared by
      HPLC, two unknown metabolites were found and these were excreted as the
      conjugated forms. Metabolites 1 and 2 were tested by LC/MS and LC/MS/MS and both
      had parent ions at m/z 325. The fragment ion of metabolite 1 was at m/z 263 and
      ions for metabolite 2 were m/z 307 [MH - H(2)O](+), 289, 279 and 241. LC/MS/MS of
      m/z 263 as the parent ion of metabolite 1 gave fragment ions at m/z 245 and 217,
      which were assumed to be [263 - H(2)O](+) and [235 - H(2)O](+), respectively. The
      trimethylsilyl (TMS)-enol-TMS ether derivative of gestrinone displayed three
      peaks in its GC/MS chromatogram, formed by tautomerism.

PMID- 10962497
TI  - Introduction to the BELLE newsletter: special issue on caloric restriction and
      hormesis.

PMID- 10962498
TI  - Does caloric restriction induce hormesis?
AB  - The question of whether caloric restriction (CR) is hormetic is addressed in
      terms of two common definitions of the term. In terms of the older definition,
      i.e., a growth-stimulatory effect when lower doses of a compound which resulted
      in growth inhibition at higher doses, CR is better characterized as a co-hormetic
      (i.e., a paradigm which at relatively "low doses," in combination with some
      stimulus, will evince increased growth (proliferation) and at higher "doses" will
      inhibit this increased proliferation) rather than a hormetic agent. Mechanisms
      such as cellular selection of cellular subpopulations, increases in receptor
      efficiency, and preservation of cellular proliferative potential can interact
      with agents and produce increased growth as long as the CR is not too severe. In
      terms of a broader definition, i.e., nonmonotonic dose-response behavior of a
      compound for any adverse response, CR appears to be hormetic, both as a result of
      body weight (BW) loss and other potential mechanisms. The impact of changes in
      BW, or frank CR, can be considered a component of every test for hormesis, and is
      thus capable for interaction with any other agent. The changes that BW loss (or
      CR) induce are so profound that any aspect of an agent's action - metabolism,
      pharmacokinetics, pharmacodynamics - can modulate the response of an organism to
      an agent. Similarly, other effects of a chemical that induce BW loss, e.g.,
      physical activity or temperature dysregulation, can also induce dose-response
      curves that appear hormetic. The interaction of the hormetic agents of BW loss
      and CR can influence agent tests. Controlling these factors may make it possible
      to dissect the key components of a hormetic response. In addition, the effects of
      CR or BW loss appear to extrapolate well across species [Colman R, Kemnitz JW.
      Aging experiments using nonhuman primates. In: Yu BP (Ed), Methods in Aging
      Research. CRC Press, Boca Raton, FL, 1999, pp. 249-267]. Thus there is some
      reason to believe that these hormetic factors may be important for humans, and
      may already be a factor for tests of potentially adverse agents already conducted
      in humans.

PMID- 10962499
TI  - Commentary: does caloric restriction induce hormesis?

PMID- 10962500
TI  - Rodent cancer bioassays - is body weight depression hormetic?

PMID- 10962501
TI  - BELLE newsletter commentary: does caloric restriction induce hormesis?

PMID- 10962502
TI  - Caloric restriction, hormesis and life history plasticity.

PMID- 10962503
TI  - Hormesis is the beneficial action resulting from the response of an organism to a
      low-intensity stressor.

PMID- 10962504
TI  - Age-specific mortality rate analyses suggest response from caloric restriction
      and hormesis are due to separate mechanisms.

PMID- 10962505
TI  - Caloric restriction, metabolic efficiency and hormesis.

PMID- 10962506
TI  - Are calories responsible for a decline in longevity?

PMID- 10962507
TI  - Is caloric restriction hormetic or is ad libitum feeding toxic?

PMID- 10962508
TI  - Does caloric restriction cause hormesis? Comments on paper by Turturro, Hass and
      Hart.

PMID- 10962509
TI  - Response to the commentaries on "Does caloric restriction induce hormesis?"

PMID- 10962510
TI  - Toxicity of ingested formalin and its management.
AB  - Formaldehyde is a physiological intermediary metabolite taking part in many
      biological process in the body. It is a constituent of many items of daily use,
      including foods. It is also used in medicine for treatment of some conditions. A
      40% solution of formaldehyde in water is known as formalin. Formalin is
      irritating, corrosive and toxic and absorbed from all surfaces of the body.
      Ingestion is rare because of alarming odour and irritant effect but documented in
      accidental, homicidal or suicidal attempts. Ingestion can lead to immediate
      deleterious effects on almost all systems of the body including gastrointestinal
      tract, central nervous system, cardiovascular system and hepato-renal system,
      causing gastrointestinal hemorrhage, cardiovascular collapse, unconsciousness or
      convulsions, severe metabolic acidosis and acute respiratory distress syndrome.
      No specific antidote is available. Treatment of toxicity is supportive care of
      the various organ systems. Multidisciplinary approach is required for proper
      management.

PMID- 10962511
TI  - Copper toxicity affects proliferation and viability of human hepatoma cells
      (HepG2 line).
AB  - In Wilson's disease and Indian childhood cirrhosis (ICC) copper accumulates in
      the liver resulting in poor hepatocyte regeneration and fibrosis. An inhibition
      of hepatocyte proliferation and an increase in cell death could account for these
      outcomes. To establish how the toxicity of this metal ion impacts upon the
      proliferation and viability of the HepG2 cells they were cultured in 4-32 microM
      copper(II) sulphate (CuSO4)). These levels were comparable to the circulatory and
      tissue concentrations of copper recorded for these two diseases. Specific uptake
      comparable to levels of copper recorded in the livers of patients with Wilson's
      disease and ICC was measured in the HepG2 cells. After 48 h acid vesicle function
      increased from 4 to 32 microM Cu2+ but significantly declined at 64 microM
      compared to the controls. Lysosomal acid phosphatase showed a concentration
      dependent decline in activity at 72 h. Cellls exposed to 64 microM Cu2+ had a
      potential doubling time (Tpot) 21 h longer than the control cells due to a
      prolonged DNA synthesis phase. At 64 microM Cu2+, increases of necrosis up to 18%
      were seen whereas comparable levels of apoptotic and necrotic cells (<5%) were
      seen below this concentration. Chronic exposure over 8 weeks impaired colony
      forming efficiency at concentrations of 16 microM Cu2+ and above. This study
      suggests that when liver cells sequester large amounts of copper, the toxic
      effects include delayed cell-cycle progression, a gradual loss of replicative
      capacity, and an increased incidence of cell death.

PMID- 10962512
TI  - Inhibitory effect of Emblica officinalis on the in vivo clastogenicity of
      benzo[a]pyrene and cyclophosphamide in mice.
AB  - Benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) are potent carcinogens/mutagens.
      Effect of Emblica officinalis extract administration on the in vivo genotoxicity
      of B[a]P and CP was studied using bone marrow chromosomal aberration and
      micronucleus induction tests in mice. Three doses (50, 250 and 500 mg/kg body
      weight) of the plant extract were administered orally for 7 consecutive days
      prior to the administration of single dose of mutagens (B[a]P 125 mg/kg oral; CP
      40 mg/kg i.p.). It was found that administration of 250 and 500 mg/kg of E.
      officinalis extract significantly inhibited the genotoxicity of B[a]P as well as
      CP in both the assay systems. Administration of 50 mg/kg of the plant extract had
      no inhibitory effect. Vitamin C, a major constituent of E. officinalis when
      administered at dose level of 9 mg/kg b.w. (the approximate estimated amount
      present in the highest dose of plant extract, i.e. 500 mg) for 7 days did inhibit
      chromosomal aberrations and micronuclei induction, but not in a significant
      manner. Effect of administration of the abovementioned effective doses (250 and
      500 mg/kg oral for 7 days) of plant extract and vitamin C (9 mg/kg oral for 7
      days) on the hepatic activation and detoxification enzymes was also studied.
      Significant induction in the levels of glutathione content (GSH) and of
      antioxidant and detoxification enzymes viz., glutathione peroxidase (GPx),
      glutathione reductase (GR) and glutathione-S transferase (GST) resulted from
      plant extract treatment to animals. On the other hand, cytochrome P 450 level was
      significantly decreased in the plant-extract-treated animals. There was no
      significant change in cytochrome P 450, GSH contents and activities of enzymes on
      treatment with vitamin C. The data indicate that the possible mechanism of
      inhibition by plant extract is mediated by its modulatory effect on hepatic
      activation and disposition processes.

PMID- 10962513
TI  - Systolic versus diastolic pressure: paradigm shift or cycle?

PMID- 10962514
TI  - Endothelial vasomotor dysfunction in hypertension.

PMID- 10962515
TI  - Failure of L-arginine to induce hypotension in patients with a history of
      accelerated-malignant hypertension.
AB  - A profound elevation of blood pressure on exercises or after withdrawal of
      antihypertensive drugs has been reported in patients with a history of
      accelerated-malignant hypertension. We tested the hypothesis that severe
      endothelial dysfunction is responsible for the profound hypertensive response in
      these patients. Responses of blood pressure, heart rate and plasma cyclic
      guanosine monophosphate to intravenously infused L-arginine, a precursor of
      nitric oxide, was investigated in hypertensive patients with (group A) or without
      any history of accelerated-malignant hypertension (group B) in order to evaluate
      endothelial function. Casual blood pressure or severity of hypertension was not
      different between group A and B. Infusion of L-arginine decreased mean blood
      pressure in group B (97.4 +/- 8.7 to 81.7 +/- 6.9 mm Hg), but not in group A
      (99.0 +/- 10.2 to 101.5 +/- 8.7 mm Hg). Plasma levels of cyclic guanosine
      monophosphate were increased after infusion of L-arginine in group B (5.4 +/- 2.0
      to 7. 7 +/- 1.7 pmol/ml, P< 0.01), while no significant changes were observed in
      group A (5.4 +/- 2.1 to 5.9 +/- 2.1 pmol/ml). There was a significant correlation
      between decrease in mean blood pressure and increase in plasma levels of cyclic
      guanosine monophosphate (r = 0.83, P < 0.001). The results indicated that much
      more severe endothelial dysfunction is present in hypertensive patients with a
      history of accelerated-malignant hypertension as compared to those without the
      history. The difference in the endothelial function may account for the different
      pressor responses to exercises or other stimuli observed in hypertensive patients
      with and without a history of accelerated-malignant hypertension. Journal of
      Human Hypertension (2000) 14, 485-488

PMID- 10962516
TI  - Blood pressure patterns and cardiovascular risk factors in rural and urban
      gambian communities.
AB  - Hypertension is emerging as an important public health problem in sub-Saharan
      Africa. We studied blood pressure (BP) patterns, hypertension and other
      cardiovascular risk factors in a rural and an urban area of The Gambia. A total
      of 5389 adults (> or =15 years) were selected by cluster sampling in the capital
      Banjul and a rural area around Farafenni. A questionnaire was completed, BP,
      pulse rate, height and weight were recorded. Glucose was measured 2 h after a 75
      g glucose load among participants > or =35 years (n = 2301); total cholesterol,
      triglycerides, creatinine and uric acid were measured among a stratified
      subsample (n = 1075). A total of 7.1% of the study participants had a BP > or
      =160/95 mm Hg; 18.4% of them had a BP > or =140/90 mm Hg. BP was significantly
      higher in the urban area. BP increased with age in both sexes in both areas.
      Increasing age was the major independent risk factor for hypertension. Related
      cardiovascular risk factors (obesity, diabetes and hyperlipidaemia) were
      significantly more prevalent in the urban area and among hypertensives; 17% of
      measured hypertensives were aware of this, 73% of people who reported to have
      been diagnosed as hypertensive before had discontinued treatment; 56% of those
      who reported being on treatment were normotensive. We conclude that hypertension
      is no longer rare in either urban or rural Gambians. In the urban site
      hypertension and related cardiovascular risk factors were more prevalent.
      Compliance with treatment was low. Interventions aimed at modifying risk factors
      at the population level, and at improving control of diagnosed hypertension are
      essential to prevent future increases of cardiovascular morbidity and mortality.
      In view of limited resources and feasibility of intervention in rural Gambia,
      these could initially be directed towards urbanised populations.

PMID- 10962518
TI  - Relationship between plasma renin profile and leptinaemia in patients with
      essential hypertension.
AB  - Both leptin and the renin-angiotensin system (RAS) can influence the activity of
      the sympathetic nervous system, water and electrolyte metabolism as well as
      vascular remodelling, which are all involved in the regulation of arterial blood
      pressure. Thus leptin and the RAS may act together in the pathogenesis of
      essential hypertension. The present study aimed to answer the following question:
      does an interrelationship exist between leptinaemia and the plasma renin activity
      (PRA) profile in normotensive and hypertensive subjects? Forty-three patients
      with essential hypertension (EHP) (23 females, 20 males, mean age 39.0 +/- 1.8
      years, mean body mass index (BMI) 26. 8 +/- 0.6 kg/m2, mean arterial pressure
      (MAP) 123 +/- 2 mm Hg) and 32 healthy subjects (NTS) (18 females, 14 males, mean
      age 38.6 +/- 2. 2 years, mean BMI 25.4 +/- 0.5 kg/m2, MAP 95 +/- 1 mm Hg) were
      examined. Plasma leptin levels were estimated once after the administration of a
      diet containing 100-120 mmol Na/day and after overnight 8-h recumbency. PRA was
      estimated twice: first after the administration of a diet containing 100-120 mmol
      Na day and overnight 8-h recumbency (PRA I), and a second time after 3 days of
      sodium restriction (20 mmol Na/day), and 3 h of upright position (PRA II).
      Antihypertensive drugs were withdrawn 7 days before the study. In EHP plasma
      leptin concentration was insignificantly higher than in NTS (14.0 +/- 2.0 vs10.8
      +/- 1.5 ng/ml respectively). Only females with hypertension showed a significant
      positive correlation between plasma leptin concentrations (expressed as the
      logarithmic values) and PRA I. Using the multiple regression analysis, in all
      studied subjects (EHP and NTS together), logarithm (log) of plasma leptin
      concentrations was significantly related to gender, BMI and MAP. Multiple
      regression analysis performed separately for EHP or NTS revealed a significant
      relation of log plasma leptin concentrations with gender and BMI. A significant
      correlation was found between log leptinaemia values and BMI, mean and systolic
      blood pressure respectively if the whole group of subjects (EHP+NTS) or EHP and
      NTS separately were analysed. Especially in hypertensive women a highly
      significant correlation was found between log plasma leptin concentrations and
      MAP. We conclude that a significant relationship between leptinaemia and PRA does
      exist in females with EH and that participation of both PRA and leptin in the
      pathogenesis of EH in females seems to be likely.

PMID- 10962517
TI  - Prevalence, awareness and management of hypertension in a recently urbanised
      community, eastern Jordan.
AB  - The objectives of this study were to: (1) estimate the magnitude of hypertension,
      and its levels of awareness and control of hypertension among a recently
      urbanised community of Jordanian aborigines; and (2) to compare the study
      findings with findings from other Jordanian communities. A sample was randomly
      selected from the roster of all inhabitants of the community aged 25 years or
      older. Data on 545 subjects included in the sample were collected during the
      months of January and February of 1995. A total of 89 (16.3%) subjects were
      suffering hypertension defined as systolic blood pressure > or =160 mm Hg and/or
      diastolic blood pressure > or =95 mm Hg or on antihypertensive medication.
      Prevalence rate of hypertension was comparable to that reported from other
      Jordanian communities who have experienced an urban lifestyle earlier than the
      reference community. Logistic regression analysis indicated that hypertension was
      positively associated with age, illiteracy, body mass index, family history of
      hypertension, and diabetes mellitus. No association was detected between
      hypertension and each of gender, smoking, and total serum cholesterol. This study
      showed that the vast majority of hypertensive patients (82.0%) were aware of
      their diagnosis. However, more than two-thirds (68.5%) of those aware of their
      diagnosis did not achieve control of their hypertension. In conclusion,
      hypertension is a common public health problem in this community and that the
      hypertension management programme is far below the optimal level.

PMID- 10962519
TI  - Association of hypertensive status and its drug treatment with lipid and
      haemostatic factors in middle-aged men: the PRIME study.
AB  - AIMS: To assess the association of hypertensive status and antihypertensive drug
      treatment with lipid and haemostatic levels in middle-aged men. METHODS AND
      RESULTS: Hypertensive status, antihypertensive drug treatment, total and high
      density lipoprotein (HDL) cholesterol, triglyceride, apoproteins A-I and B,
      lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plasminogen activator inhibitor
      1 (PAI-1) activity and factor VII were assessed in a sample of men 50-59 years
      living in France (n = 7050) and Northern Ireland (n = 2374). After adjustment for
      age, body mass index, smoking status, educational level, country, alcohol
      drinking and hypolipidaemic drug treatment, untreated hypertensive subjects had
      higher levels of total cholesterol, triglyceride, apoproteins A-I and B and PAI-I
      activity than normotensive subjects. On univariate analysis, diuretics decreased
      total and HDL-cholesterol and apoproteins A-I and B; those differences remained
      after multivariate adjustment. Treatment with beta-blockers decreased total and
      HDL-cholesterol, apoprotein A-I and LpA-I, and this effect remained after
      multivariate adjustment. Calcium channel blockers decreased total cholesterol and
      apoproteins A-I and B; those differences remained significant after multivariate
      adjustment. ACE inhibitors decreased total cholesterol, triglycerides, apoprotein
      B and LpE:B; and this effect remained after multivariate adjustment. Analysis of
      the subjects on monotherapy showed beta-blockers to decrease total cholesterol
      and HDL parameters and angiotensin-converting enzyme (ACE) inhibitors to decrease
      low-density lipoprotein (LDL)-related parameters, while no effect was found for
      the other antihypertensive drugs. CONCLUSIONS: Hypertensive status is associated
      with an unfavourable lipid and haemostatic profile in middle-aged men.
      Antihypertensive treatment with beta-blockers decreases HDL parameters, whereas
      treatment with ACE inhibitors appears to decrease total cholesterol and LDL
      related parameters.

PMID- 10962520
TI  - Antihypertensive effect of valyl-tyrosine, a short chain peptide derived from
      sardine muscle hydrolyzate, on mild hypertensive subjects.
AB  - The present study was conducted to determine whether Valyl-Tyrosine (VY) has an
      antihypertensive effect on high-normal blood pressure and mild essential
      hypertension, as well as spontaneous hypertensive rats (SHR). A randomised double
      blind placebo-controlled study was carried out on 29 volunteers. A 100-ml drink
      containing 3 mg of VY and a 100-ml placebo drink were prepared. The subjects were
      grouped as VY(16M/1F, 45.5 +/- 3.2 years, 146.4 +/- 2.3/90.5 +/- 1.8 mm Hg) and
      the placebo (P) (11 M/1F, 48.8 +/- 3.0 years, 145.5 +/- 2.4/92.3 +/- 1.8 mm Hg).
      At 3 weeks of the control (C) period, a VY- or P-drink was administered twice a
      day for 4 weeks in the experimental (E) period and during the 4-week recovery
      period, neither drink was given to either group. Blood pressure (BP) was measured
      every week in the morning in the sitting position. Blood specimens were taken on
      the last day of the C and E periods. In the VY-group, reduction in systolic (S)
      and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0. 001) at 1 week, and 9.3 and
      5.2 mm Hg (P < 0.001) at 4 weeks, following the start of the E period,
      respectively. Neither SBP nor DBP changed in the P-group. BP in the VY-group
      increased gradually by the end of the recovery period. Plasma angiotensin (Ang) I
      and VY concentrations significantly increased while Ang II and aldosterone
      significantly decreased after VY administration in the VY-group. VY appeared to
      have a significant antihypertensive effect on mild hypertensive subjects via Ang
      I-converting enzyme inhibition, as well as SHR, but no adverse effects could be
      detected at all.

PMID- 10962521
TI  - Effect of antihypertensive treatment on office and self-measured blood pressure:
      the Autodil study.
AB  - OBJECTIVE: To examine prospectively the effects of antihypertensive therapy on
      office blood pressure (BP) and home BP, in a large-scale hypertensive population
      followed by their general practitioners. PATIENTS: A total of 760 hypertensive
      patients either never treated or after a 2-week washout period, aged 18-75 years,
      with a diastolic office BP between 95 and 110 mm Hg and a systolic office BP
      below 180 mm Hg. METHODS: Patients measured their BP at home using an automated
      printer-equipped oscillometric device (OMRON-HEM 705 CP) twice daily for 8 days
      before the visit to their general practitioner who recorded three office BP.
      These measurements were performed before and after 8 weeks of antihypertensive
      therapy with sustained-release diltiazem 300 mg once daily. RESULTS: Diltiazem
      reduced systolic and diastolic office BP and home BP and heart rate (P < 0.01).
      Systolic and diastolic office BP were higher than home BP before (P < 0.01) but
      not during treatment. Correlation coefficients between the two methods before and
      during therapy were 0.6 and 0.7 for systolic BP and 0.4 and 0.6 for diastolic BP
      (P < 0. 01). Both methods did not agree equally throughout the range of BP: home
      BP was higher than office BP for high values and lower for low values.
      CONCLUSION: The results show that BP measured at home by patients can be higher
      than office BP in the highest range of BP. Journal of Human Hypertension (2000)
      14, 525-529

PMID- 10962522
TI  - Central aortic blood pressure measurements.

PMID- 10962523
TI  - Factors influencing the development of malignant hypertension in nigeria
AB  - Hypertension prevalence rates remain comparatively low in Nigeria, although the
      associated morbidity and mortality including that due to malignant hypertension
      (MHT) is considerable. To determine the factors that may be associated with the
      development of MHT we compared 74 patients with essential MHT (age 48 +/- 9
      years, 59 male, blood pressure (BP) 234 +/- 31/140 +/- 17 mm Hg) with 74, age,
      gender and BP-matched patients with essential benign hypertension (BHT) (49 +/- 8
      years, 60 male, 227 +/- 26/136 +/- 15 mm Hg). Body mass index was higher in the
      BHT group by 1.3 (95% Cl: 0.5 to 2.1, P < 0.01). In the subset (25 MHT, 43 BHT)
      in whom hypertension had been diagnosed before presentation, duration of
      hypertension was shorter (P < 0.05) in the MHT group. Patients with MHT, were
      more likely to have been receiving inadequate therapy in the months before (OR
      2.7, 95% Cl: 1.4 to 5.4), showed a decreasing proportion with increasing socio
      economic class (chi2 = 5.79, P < 0.02) and had been exposed to a greater degree
      of stress (OR 3.5, 95% Cl: 1.7 to 7. 1). Smoking (OR 1.1, 0.6 to 2.3), alcohol
      use (OR 0.9, 0.5 to 1.8) and contraceptive pill use (OR 0.9, 0.1 to 8.6) did not
      impart excess risk. MHT is associated with the underprivileged and measures aimed
      at raising the general awareness and the socio-economic level of the people are
      expected to produce a decline in the incidence of MHT. Journal of Human
      Hypertension (2000) 14, 171-174.

PMID- 10962524
TI  - Neoplastic meningitis: diagnosis and treatment considerations.
AB  - Neoplastic meningitis is an increasingly recognized complication of advanced
      metastatic cancer and, if left undiagnosed or untreated, is characterized by
      rapid neurologic deterioration and death. Thus, the diagnosis and treatment of
      neoplastic meningitis present challenges for the clinical oncologist. The
      diagnosis of neoplastic meningitis is based on clinical signs and symptoms,
      laboratory analysis of cerebrospinal fluid to determine cell count and cytology,
      and analysis of neuroimaging studies for evidence of leptomeningeal or cranial
      nerve enhancement. Once diagnosed, conventional treatment regimens may include
      radiotherapy combined with systemic or intrathecal chemotherapy, often with the
      antimetabolites cytarabine and/or methotrexate. However, the prognosis for
      neoplastic meningitis secondary to an underlying solid tumor or recurrent
      leukemia is poor with conventional treatment regimens. Therefore, novel agents
      for intrathecal administration, including DepoCyttrade mark, mafosfamide, and
      topotecan, or novel therapeutic approaches, including conjugated monoclonal
      antibodies and immunotoxins or gene therapy, are currently under investigation.
      Such new agents and therapeutic approaches will facilitate the development of
      effective treatment strategies and will ultimately improve the outcome for
      patients with this devastating disease. This article provides an overview of the
      approaches to the diagnosis, evaluation, and treatment of neoplastic meningitis.

PMID- 10962525
TI  - Global approach to hepatic metastases from colorectal cancer: indication and
      outcome of intra-arterial chemotherapy and other hepatic-directed treatments.
AB  - Liver metastases of colorectal cancer is present in more than 20% of new
      diagnosed patients and in 40-60% of relapsed patients. It is a life-threatening
      prognostic aspect. Hepatic resection, when possible, is the best therapeutic
      modality, although the overall survival rate is still low (30%). Angiography and
      intraoperative ultrasonography are useful for resection. The number of hepatic
      metastases and the surgical margin are probably the most significant prognostic
      factors. Colorectal cancer may spread predominantly to the liver making regional
      treatment strategies viable options. Subtotal hepatic resections and
      segmentectomies are potentially curable procedures for single or small numbers of
      hepatic metastases without other sites of disease. However, there have been no
      prospective randomized trials comparing patients with unresected liver metastases
      and resected metastases. Regional chemotherapy with floxuridine seems usefull
      combined with hepatic resection or as palliative therapy. Gastric ulcer and
      biliary sclerosis are the main related toxicities. Patients with localized,
      unresectable hepatic metastases or concomitant bad medical condition may be
      candidates for radiation, percutaneous ethanol injection, cryosurgery,
      percutaneous radiofrequency, hypoxic flow-stop perfusions with bioreductive
      alkylating agents, hepatic arterial ligation, embolization and chemoembolization.
      These new hepatic-directed modalities of treatment are being investigated and may
      offer new approaches to providing palliation and prolonging survival. This review
      will report the possibilities of intra-arterial chemotherapy and other novel
      hepatic-directed approaches to the treatment of liver metastases from colorectal
      cancer.

PMID- 10962526
TI  - Routine bone scintigraphy is of limited value in the clinical assessment of
      untreated patients with Hodgkin's disease.
AB  - The aim of this retrospective study was to evaluate the role of routinely
      performed bone scintigraphy in the clinical assessment of patients with
      previously untreated Hodgkin's disease (HD). One-hundred and eighty-three
      patients with a median age of 31 yrs (range 16-85) with newly diagnosed HD
      underwent bone scintigraphy between 1972 and 1995. Bone scintigraphies and
      skeletal X-ray examinations of patients with any pathological scintigraphic
      finding were reassessed. Initially HD bone involvement could be excluded in 173
      (95%) of the patients. Among the remaining ten patients, two had diffuse
      increased tracer uptake but X-rays were normal. One of these patients was
      classified as normal with regard to HD bone involvement. A bone marrow
      scintigraphy examination and regression of changes following therapy supported
      primary osseous involvement in the other patient. Five patients had focal
      scintigraphic abnormalities but skeletal X-rays remained negative; three of these
      five patients reported pain in the scintigraphically affected areas, and
      therefore the suspicion of bone involvement was strong. The remaining three
      patients had focal findings both on bone scintigraphy and skeletal X-ray
      examination and were considered as having osseous HD involvement. All seven
      patients judged to have HD bone involvement were planned to receive combination
      chemotherapy up-front, irrespective of the scintigraphic findings. In this series
      of 183 patients bone involvement was detected in seven patients based on bone
      scintigraphy/symptoms (n=3), bone marrow scintigraphy/symptoms (n=1), and bone
      scintigraphy/X-ray examination (n=3). The decision to give multiagent
      chemotherapy to all patients was not influenced by scintigraphic findings.
      Therefore, routine bone scintigraphy seems to be of limited value in the clinical
      assessment of untreated patients with HD.

PMID- 10962528
TI  - Immunohistochemical investigation of migration inhibitory factor-related protein
      (MRP)-14 expression in hepatocellular carcinoma.
AB  - Migration inhibitory factor-related protein (MRP)-8 and -14 belong to the S-100
      protein family and are associated with myeloid cell differentiation. MRP is also
      expressed in some epithelia. However, there are few reports for the investigation
      on carcinomas. Using the monoclonal antibody 60B8 against MRP-14, we carried out
      the immunohistochemical evalution of MRP-14 expression in 70 cases of
      hepatocellular carcinoma (HCC), and examined the relation to tumor
      differentiation and vascular invasion. Positively stained tumor cells were
      detected in 32 cases, all of which belonged to grade II (7/30) or grade III
      (25/25) of the Edmondson-Steiner classification. In particular, the grade III HCC
      showed a significantly greater positive reaction. Immunopositivity in the non
      carcinomatous hepatocytes and bile duct epithelia was not observed. These
      findings suggested that malignant hepatocytes newly express MRP-14 and that the
      neo-expression in differentiated HCC is related to the tumor differentiation and
      shows higher correlation in the poorly differentiated carcinomas. Furthermore,
      the cholangiocellular carcinoma and metastatic adenocarcinoma as control
      materials also presented a more marked immunoreactivity for MRP-14 in the poorly
      differentiated carcinomas, in a similar manner with the findings of the HCC.
      Accordingly, MRP is considered to be frequently neo-expressed in poorly
      differentiated carcinomas. MRP-14 expression rate in the 48 HCC cases with
      vascular invasion was 56%, showing no significant difference compared with non
      invasive tumors.

PMID- 10962529
TI  - CD68+/CD83+/CD1a- dendritic cell subsets from patients with multiple myeloma are
      not infected with human herpesvirus 8.
AB  - Recently, a subset of dendritic cells with the phenotype CD68+/CD83+/CD1a-,
      present in patients with multiple myeloma (MM), was reported to be infected with
      human herpesvirus 8 (HHV-8). Therefore we wished to clarify whether HHV-8
      infection might be related to the pathogenesis of MM. In an attempt to identify
      HHV-8 infected cells in patients with MM, long-term bone marrow cultures from 8
      MM patients and dendritic cell cultures from 11 MM patients were established. In
      addition, fresh bone marrow aspirates from 10 MM and 10 patients with monoclonal
      gammopathy of undetermined significance (MGUS) were included in the study. All
      samples were analysed by a sensitive semi-nested PCR assay and were found to be
      consistently PCR negative. Phenotyping of day 7 dendritic cell cultures
      demonstrated the presence of a sufficient number of CD68+/CD1a- and CD83+/CD1a-
      cells. However, to exclude the presence of infrequent HHV-8 infected cells, the
      CD68+/CD1a- subset from 3 dendritic cell cultures was sorted in numbers of 105
      for each PCR test, and again a negative PCR result was observed. This study
      documents that the CD68+/CD83+/CD1a- dendritic cells in patients with MM are not
      generally infected with HHV-8 and, as a consequence, it is unlikely that HHV-8
      plays a role in the pathogenesis of MM.

PMID- 10962527
TI  - Selected risk factors for transitional cell bladder cancer.
AB  - Cancer of the bladder has long been associated with environmental risk factors,
      such as occupational hazards and smoking. The aim of the current study was to
      evaluate the contribution of known risk factors on a community basis in the
      1990s, in view of the recent worldwide efforts to control environmental hazards.
      The study population included 140 male patients and 280 matched controls.
      Information on demographic data, occupational exposure, smoking habits and
      disease history was obtained by personal interviews. Our study confirmed the role
      of industrial occupation (OR=2.21; 95% Cl=1. 21-4.02) and exposure to 3 or more
      metals (OR=3.65; 95% Cl=1.21-11. 08) as risk factors. Prostate enlargement was
      also found significant, but probably not causal (OR=2.23; 95% Cl=1.29-3.87).
      Surprisingly, smoking showed only an inconsistent association with higher rates
      among those who started to smoke before 18 years of age (OR=2.64; 95% Cl=1.4
      4.99) and those who smoked more than 30 cigarettes per day (OR=1.82; 95% Cl=0.95
      3.49). The above data suggest that current efforts to reduce the load of bladder
      cancer in the population, via environmental measures, have not as yet yielded
      significant effects.

PMID- 10962530
TI  - CN3OP: an active regimen in patients with relapsed/refractory Hodgkin's lymphoma.
AB  - Patients with recurrent or refractory Hodgkin's and non-Hodgkin's lymphoma are
      increasingly being treated with high-dose therapy and hematopoietic cell
      transplantation. As minimal disease status at the time of transplant has been a
      repeatedly proven significant prognostic factor for long-term survival, effective
      initial cytoreduction is an important step in the process. Modern chemotherapy
      programs for Hodgkin's lymphoma include virtually all active agents and little is
      left for effective salvage. Mitoxantrone is an active agent in lymphoma that is
      not generally used in first-line treatment. The aim of this study was to
      determine toxicity and response rate to CN3OP (fractionated mitoxantrone 6 mg/m2
      on days 1, 2, and 3, combined with standard dose cyclophosphamide, vincristine,
      and prednisone) in 44 patients with relapsed or refractory lymphoma. Most of
      patients had advanced disease and one or more extranodal sites at relapse. Median
      response duration to immediate past therapy was four months, and one third of
      patients had not responded to prior treatment. A median of 4 cycles of CN3OP were
      given per patient for a total of 173 cycles. Grade III-IV neutropenia occured in
      53% of cycles, Grade I-III mucositis in 24%, and Grade I-III infection in 17% of
      cycles. Of 34 evaluable patients with Hodgkin's lymphoma 12 (35%) achieved
      complete remission (CR) and 15 (44%) partial remission (PR) for an overall
      response rate of 79%. Two of five evaluable non-Hodgkin's lymphoma patients
      responded with PR. Median overall survival and event free survival in the entire
      group was 29 months and 11 months respectively. At this time 16 patients have
      died; 12 of lymphoma, two of unknown cause and two of other causes. Complete
      response to CN3OP correlated with survival. CN3OP is an effective and safe
      regimen for cytoreduction in Hodgkin's lymphoma patients pretreated with
      doxorubicin/alkylator/etoposide-containing primary therapies.

PMID- 10962531
TI  - Rituximab anti-CD20 monoclonal antibody induces marked but transient reductions
      of peripheral blood lymphocytes in chronic lymphocytic leukaemia patients.
AB  - Rituximab has been recently proposed as an effective non-chemotherapeutic option
      for patients with follicle centre lymphoma (FCL). However, less is known on its
      role in chronic lymphocytic leukaemia (CLL). We thus decided to assess its
      effectiveness on a panel of 7 patients with refractory or relapsed CLL. Mild (5
      patients) or severe (1 patient) adverse reactions were observed during the first
      hours of Rituximab infusion, almost exclusively at the first course. Symptoms
      rapidly subsided with temporary drug withdrawal and low dose steroids. All
      patients could receive the whole scheduled treatment. A striking reduction of
      peripheral blood (PB) lymphocyte counts was observed in all patients (median 93%;
      range 57-99%). However, Rituximab was poorly effective towards nodal and splenic
      disease. Patients required additional treatment after a median time of 70 d
      (range: 20-180 d). Our data show that Rituximab delivery in CLL patients is
      feasible and has an acceptable toxicity, although it probably does not represent
      an ideal treatment option when delivered using schedules originally designed for
      FCL patients. However, responses observed at PB level suggest that Rituximab has
      an activity which is not negligible and deserves further investigation in CLL.
      Future approaches will be directed to the development of alternative schedules
      which may include dose intensification, combination of Rituximab and
      chemotherapy, and in vivo purging of peripheral blood progenitor cell harvests
      for autografting procedures.

PMID- 10962532
TI  - HIV-1 tat induced apoptosis of T-cells is not mediated by TGF-beta.
AB  - Recent reports have demonstrated that the HIV-1 transactivator protein, tat,
      induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood
      mononuclear cells, and stimulates a cascade of events resulting in up-regulation
      of the potent immunosuppressive cytokine, transforming growth factor-beta (TGF
      beta). In this study we evaluated the ability of TGF-beta to mediate tat induced
      apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF
      beta1 or a combination of tat and pan-specific TGF-beta neutralizing antibodies
      showed little change in the amount of apoptosis. When treated with pan-specific
      TGF-beta neutralizing antibodies, Jurkat cells that stably express tat protein
      (Jurkat-tat ) showed only a modest decrease in apoptosis, while CEM-TART cells
      (CEM T-cells expressing both HIV-1 tat and rev ) demonstrated little change in
      the amount of apoptosis. In conclusion, we have demonstrated that TGF-beta does
      not play a significant role in mediating tat induced T-cell apoptosis.

PMID- 10962533
TI  - Risk factors for side effects during first infusion of rituximab-definition of a
      low risk group.
AB  - Side effects from the first infusion of the monoclonal anti-CD20 antibody,
      rituximab, 375 mg/m2 was documented in 47 treatments (37 patients) and correlated
      to tumour mass and interval to previous cytostatic treatment. A significant
      correlation was found with less side effects in patients with a low tumour mass
      and/or if chemotherapy was recently administered. It is difficult to differ
      between these two parameters as they covariate, i.e. the majority of patients
      without or with a minimal tumour burden were recently treated with cytostatics.
      The reason why these patients have no or minimal side effects may be due to low
      numbers of CD20 positive cells in the circulation. The finding of a low-risk
      group for side effects from the first infusion of rituximab; has practical
      clinical implications, for example, hospitalization can be avoided. Concerning
      side effects, it may be an advantage to give rituximab after the introduction of
      successful chemotherapy.

PMID- 10962534
TI  - Pregnancy after treatment of secondary acute promyelocytic leukemia following
      Hodgkin's disease: a case report.
AB  - The authors report a case of therapy-related acute promyelocytic leukemia (t
      APL), with typical cytogenetic translocation t(15;17), which appeared following
      chemotherapy (ABVD), and radiotherapy for Hodgkin's disease (IIB). After
      treatment with all-trans retinoic acid (Vesanoid(R) 45 mg/m2 daily) complete
      remission of t-APL was achieved. Then only one course of chemotherapy '3+7'
      (doxorubicin 45 mg/m2 1-3 d, cytosar 200 mg/m2 1-7d) was applied and the patient
      interrupted further treatment in July 1994. Four years later she had a normal
      pregnancy and delivered a healthy female infant in December 1998.

PMID- 10962535
TI  - Retreatment with chimeric CD 20 monoclonal antibody in a patient with nodal
      marginal zone B-cell lymphoma.
AB  - A patient with advanced and chemotherapy-refractory nodal marginal zone B-cell
      lymphoma was given a course of chimeric CD 20 monoclonal antibody Rituximab.
      Partial response was observed without any major toxicities. Retreatment with
      Rituximab for disease progression six months after the first course led to
      partial remission. Adjuvant radiotherapy was given for the residual disease and,
      currently, patient's disease remains stable eight months after the second course
      of Rituximab. This case demonstrates the therapeutic efficacy and feasibility of
      retreatment with Rituximab for relapsed or refractory low grade lymphoma.

PMID- 10962536
TI  - A more favourable clinical course of lymphoma relapsing after high-dose therapy:
      evidence of tumour heterogeneity?
AB  - Patients with Hodgkin's disease (HD) or large cell lymphomas who relapse after
      conventional chemotherapy have a poor prognosis without high-dose chemotherapy
      and stem cell transplantation (HDCT). Patients who relapse after HDCT have an
      extremely poor outcome. In the present study we describe four patients with
      relapsed HD (n=1) and large cell lymphomas (n=3) after HDCT. All had an
      aggressive clinical course before HDT. At relapse, however, they all have had
      prolonged remissions and/or spontaneous regressions on mild or no treatment.
      Possible explanations could be selection of less malignant clones or a lymphoma
      controlled by the immune system. The mechanisms are, however, unknown but warrant
      further studies of the molecular biology in these and similar cases.

PMID- 10962537
TI  - Disseminated Burkitt's-like lymphoma during pregnancy.
AB  - The occurrence of Burkitt's-like lymphoma (BL) during pregnancy is rarely
      diagnosed and its outcome is poor. A case of BL localized in the uterus, ovaries
      and breast during the course of pregnancy is presented. The patient was treated
      with a combination of surgery and chemotherapy and was disease-free for 6 months
      after the diagnosis.

PMID- 10962538
TI  - Primary pancreatic lymphoma: a case report, literature review, and proposal for
      nomenclature.
AB  - Primary neoplasms of the pancreas are most often adenocarcinoma. Non-Hodgkin's
      lymphoma (NHL) involving the pancreas is less common but well documented; the
      pancreas as the primary site of NHL is rare. The majority of patients with
      pancreatic cancer, whether it is adenocarcinoma or lymphoma, present with a mass
      in the head of the gland. Pancreatic lymphoma is often described as a large
      homogeneous mass with extra-pancreatic extension, with or without associated
      lymphadenopathy. Less common presentations are masses in the body or tail, or
      more rarely diffuse involvement of the pancreas. We present a case of diffuse
      pancreatic lymphoma with extra-pancreatic dissemination to the spleen and lymph
      nodes, and review the literature on pancreatic lymphoma. Because the definition
      of pancreatic lymphoma and primary pancreatic lymphoma varies, we also propose a
      nomenclature system to make future studies of pancreatic lymphoma more
      comparable.

PMID- 10962539
TI  - Aplastic anemia: pathophysiology and treatment

PMID- 10962540
TI  - A step towards globalization

PMID- 10962541
TI  - Enhanced T cell responsiveness to citrulline-containing myelin basic protein in
      multiple sclerosis patients.
AB  - Myelin basic protein (MBP), a candidate autoantigen in multiple sclerosis (MS),
      exists in different isoforms and charge isomers generated by differential
      splicing of exons and by a combination of posttranslational modifications,
      respectively. These various isoforms and charge isomers of MBP vary in abundance
      and most likely serve different functions during myelinogenesis and
      remyelination. The least cationic among the charge isomers of MBP is
      citrullinated and is referred to as MBP-C8. MBP-C8 is relatively increased in the
      population of MBP isomers in more developmentally immature myelin and in MS brain
      tissue. In a previous study, we found that MBP-C8-reactive T cells could be
      detected in CD4+ T cell lines (TCL) generated with MBP from both MS patients and
      normal controls. Here, we examined the frequency and peptide specificity of MBP
      C8-specific TCL generated with MBP-C8 in MS patients and controls. Ten subjects
      grouped in five sets, each an MS patient and a control, were studied. In all
      cases, the MS patient had either a higher overall number of MBP-C8-responding
      lines, responded with greater sensitivity to the MBP-C8 antigen or both. Few
      lines responded to the MBP-C8 peptides but, if they did, they appeared to be
      specific to the carboxyl-half of the MBP-C8 molecule. Given the large amounts of
      citrullinated MBP in MS brain tissue, a preferential T cell response to MBP-C8
      may be involved in the induction and perpetuation of this disease. Multiple
      Sclerosis (2000) 6 220 - 225

PMID- 10962542
TI  - Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on
      susceptibility, clinical type and progression rate.
AB  - The purpose of this study was to investigate the relation between APOE genotype
      and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined
      240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999).
      The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a
      measure of the progression rate (PR) the last registered Expanded Disability
      Status Scale (EDSS) score was divided by the time span (years) from disease onset
      until the latest assessment. The APOE genotype was determined from saliva and/or
      blood samples using PCR-techniques. The prevalence of different APOE genotypes
      was compared with the allele-distribution in a population of 361 persons from a
      Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon
      4 homozygotes was significantly higher in the MS-group as compared to controls
      (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes
      did not differ significantly. The rate of progression was significantly faster in
      the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS
      group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes
      have an increased risk of developing MS. MS patients with the APOE-epsilon
      4/epsilon 4 allele may also have an increased rate of disease progression.
      Multiple Sclerosis (2000) 6 226 - 230

PMID- 10962543
TI  - A quality network model for the daily care of multiple sclerosis.
AB  - The urgent need to optimise treatment strategies for patients with Multiple
      Sclerosis (MS) was recognised by the participants at the 1998 European Charcot
      Foundation (ECF) symposium in Nice. The 'Nice Declaration' led to the formation
      of a Task Force Essentials Group charged with developing measures of the quality
      of MS care in Europe. Algorithms for nine critical domains (disability,
      spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual
      activity) and 'educated guesses' have been developed to measure interventions and
      outcomes which reflect the quality of clinical decision-making processes. A
      generic model called a 'quality network', consisting of a group of clinics
      connected to a central server, has been successfully applied to the care of
      diabetes across Europe. This model will now be developed and applied to MS
      management, to provide clinicians with longitudinal epidemiological data and, to
      evolve treatment algorithms and further quality measures. The ECF will next
      validate the system in a 1-year pilot study using a net of 10 clinics. Finally,
      an extended European network working in a learning environment will continuously
      assess, update and improve the quality of care of MS patients. Multiple Sclerosis
      (2000) 6 231 - 236

PMID- 10962544
TI  - The precision of T1 hypointense lesion volume quantification in multiple
      sclerosis treatment trials: a multicenter study.
AB  - The volume of hypointense lesions on T1 weighted brain MRI represents an
      increasingly used MR endpoint in phase III MS treatment trials. In this study we
      evaluated the reproducibility of hypointense T1 lesion volume quantification in a
      cohort of Multiple Sclerosis (MS) patients. The gadolinium enhanced T1 weighted
      brain MR images of 33 MS patients from three European centers were used in this
      study. These images were acquired as part of a phase III trial of interferon beta
      1b in secondary progressive MS. The MRI machine manufacturers and imaging
      parameters varied according to the MRI acquisition center. Three experienced
      observers used a semi-automated local thresholding technique to quantify the
      hypointense T1 lesion volume on two occasions, separated by a delay. The intra
      and inter observer coefficients of variation were 3.7% and 4.9% respectively,
      with similar values derived for images obtained at all three sites. There was a
      generally high level of agreement between the lesion volumes obtained by the
      three raters. However, a modest but significant measurement drift was identified
      between the first and second sessions for one of the three raters, highlighting
      the very real possibility of measurement drift even for experienced observers.
      Our results support the increasing role for T1 hypointense lesion volume as an
      outcome measure in multicenter phase III MS treatment trials. Multiple Sclerosis
      (2000) 6 237 - 240

PMID- 10962545
TI  - Visuoperceptual impairment in multiple sclerosis patients diagnosed with
      neuropsychological tasks.
AB  - A comprehensive set of 31 binocular neuropsychological tasks assessing a series
      of spatial and non-spatial visuoperceptual abilities was used to study
      visuoperceptual impairment in a representative group of 49 MS-clinic patients
      exhibiting neither diagnosed ophthalmological afflictions nor major psychiatric
      diagnoses. Among these patients, true frequency rate of visuoperceptual
      impairment, i.e. of subjects failing four or more tasks, was estimated at 26%.
      The pattern of visuoperceptual impairment was non-uniform, non-selective,
      restricted and idiosyncratic. Only four tasks yielded significant rates of
      impairment. They concerned colour discrimination, the perception of the Muller
      Lyer illusion and object recognition in two separate conditions. Each of the four
      factors identified by factor analysis had an important representative (with
      factor loading >0.35) among these four tasks. Failures on these tasks correlated
      poorly. Together, the four tasks satisfactorily predicted visuoperceptual
      impairment as defined by the comprehensive set of tasks (sensitivity 86.7%;
      specificity 81.3%), but with regard to an uncontaminated criterion, their
      aggregate sensitivity and specificity was only 75 and 56% respectively.
      Visuoperceptual neuropsychological task performance related significantly but
      weakly to cognitive status, physical disability and to pyramidal, cerebellar and
      brain stem neurological signs, and did not correlate with other clinical
      neurological signs, disease duration, type of MS, a history of optic neuritis,
      depression or medication status Multiple Sclerosis (2000) 6 241 - 254

PMID- 10962546
TI  - Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis
      patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group.
AB  - In a randomized, placebo-controlled, double-blind study, glatiramer acetate
      (Copaxone) reduced the relapse rate and slowed accumulation of disability for
      patients with relapsing - remitting multiple sclerosis. Of the original 251
      patients randomized to receive glatiramer acetate or placebo, 208 chose to
      continue in an open-label study with all patients receiving active drug. The
      majority of the original double-blind cohort continues to receive glatiramer
      acetate by daily subcutaneous injection and are evaluated at 6-month intervals
      and during suspected relapse. The data reported here are from approximately 6
      years of organized evaluation, including the double-blind phase of up to 35
      months and the open-label phase of over 36 months. Daily subcutaneous injections
      of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of
      the patients who received glatiramer acetate since randomization and continued
      into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 -
      0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of
      the group who have received glatiramer acetate without interruption for 5 or more
      years, 69.3% were neurologically unchanged or have improved from baseline by at
      least one step on the Expanded Disability Status Scale (EDSS). Patients who left
      the open-label phase were surveyed by questionnaire. The majority responded,
      providing information about their current status and reasons for dropping out.
      This study demonstrates the sustained efficacy of glatiramer acetate in reducing
      the relapse rate and in slowing the accumulation of disability in patients with
      relapsing forms of multiple sclerosis. Multiple Sclerosis (2000) 6 255 - 266

PMID- 10962547
TI  - A meta-analysis of methylprednisolone in recovery from multiple sclerosis
      exacerbations.
AB  - Despite recent advances in multiple sclerosis treatment, patients experience
      relapses for which standard treatment remains glucocorticosteroids (GCS).
      However, there is limited information comparing doses or routes of administration
      for different GCS types or the benefit of GCS compared to natural recovery.
      Currently, high dose (HD) methylprednisolone (MP) is the preferred therapy. We
      conducted meta-analyses of published studies assessing MP at different doses and
      in comparison to other steroid products or no treatment. Relevant studies were
      identified through predetermined processes and five articles met the inclusion
      criteria. Three studies compared HD MP to placebo; two studies compared the
      effect of HD MP and low dose (LD) MP; only one accepted report compared HD MP to
      another GCS. This report could not be included in a meta-analysis. The meta
      analysis of HD MP vsplacebo studies indicated a mean treatment difference of 0.76
      in Expanded Disability Status Score (EDSS) changes from baseline. The meta
      analysis of HD and LD MP demonstrated no difference in EDSS change. Despite these
      rather obvious findings, these meta-analyses have been valuable in identifying
      further research questions. We recommend studies to determine optimum benefit
      related to dosage, timing for starting therapy and the most appropriate GCS type.
      Given the advances in MS therapeutics, these studies will have to include
      patients on additional disease modifying therapy. Multiple Sclerosis (2000) 6 267
      - 273

PMID- 10962548
TI  - A quantitative study of unpaid caregiving in multiple sclerosis.
AB  - Data on healthcare utilisation by MS patients of different grades of disability
      were collected using the method of a prospective diary. Professional care
      providers and unpaid caregivers noted during 4 weeks the time they spent and the
      types of support they provided. The total homecaring time of family and friends
      amounted to 4.6 and 12 h per day for the moderately and the severely disabled MS
      patients respectively. The time for unpaid core activities such as mobility help,
      nursing care and personal care of moderately and severely disabled patients
      amounted to 0.5 and 2 h per day, exceeding the time for professional medical and
      paramedical care at home. Eighty per cent of informal homecaring is provided by
      persons living with the patients, primarily the partner, who provides 60% of
      homecaring time. Severely disturbed bowel function and absence of a partner were
      associated with permanent institutionalisation. Multiple Sclerosis (2000) 6 274 -
      279

PMID- 10962549
TI  - Neuropsychological impairment in multiple sclerosis patients: the role of
      (juxta)cortical lesion on FLAIR.
AB  - In this study we evaluated the correlation between neuropsychological impairment
      (measured with the Brief Repeatable Battery Neuropsychological Tests) and
      (juxta)cortical lesions detected with FLAIR and the relative sensitivity of the
      FLAIR sequence compared to spin-echo MRI sequences in detecting (juxta)cortical
      MS lesions. A total of 39 patients with definite MS were evaluated by MRI with a
      conventional and fast spin echo sequence and fast FLAIR sequence, and
      neuropsychological tests of the Brief Repeatable Battery Neuropsychological tests
      were performed. The Z-score of all subtests were used to calculate a Cognitive
      Impairment Index. The results show that a high number of (juxta)cortical lesions
      is detected with thin slice FLAIR (30% of all lesions seen). This percentage was
      not superior to spin-echo, reflecting the thin slice thickness (3 mm) we used.
      The lesions detected with FLAIR were to a certain degree different ones than the
      lesions detected with the other techniques. While the number of non-cortical
      lesions correlated with the expanded disability status scale (r=0.32, P=0.045),
      the number of (juxta)cortical lesions detected with the FLAIR showed a
      correlation (r=0.34, P=0.035) with the Cognitive Impairment Index. Our study
      underlines the high number of (juxta)cortical lesions in MS and the value of thin
      slice FLAIR sequence to detect such lesions with MRI. It also stresses the
      importance of (juxta)cortical lesions on determining neuropsychological
      impairment. Multiple Sclerosis (2000) 6 280 - 285

PMID- 10962550
TI  - The significant change for the Timed 25-foot Walk in the multiple sclerosis
      functional composite.
AB  - The Timed 25-Foot Walk is under evaluation as a clinical tool to follow patients
      with MS. Several approaches have been taken to define a clinically significant
      change in this measurement. This study was undertaken to define the range of
      values expected for the Timed 25-Foot Walk and to correlate prospectively the
      change in walk-time that occurs during an exacerbation of MS associated with
      subjective difficulty walking. Five results from this study are emphasized. (1)
      Patients who were minimally affected by MS frequently walked 25 feet between
      three and five seconds. (2) the walk-time variability, defined as the ratio of
      the longest to the shortest walk-time, minus 1, times 100%, for three consecutive
      trials was generally 20% or less; (3) if the two fastest walk-times obtained in
      three trials were compared, the walk-time variability was almost always 10% or
      less; (4) for clinically stable individuals, the walk-times of single trials
      separated by 12 months or less generally varied less than 20%; and (5) patients
      who complained of difficulty walking, but who did not have changes otherwise
      detectable by examination, generally had a prolongation of walk-time. These
      results suggest that an increase of more than 20% in the Timed 25-Foot Walk may
      indicate a significant change in gait. Multiple Sclerosis (2000) 6 286 - 290

PMID- 10962551
TI  - Chromosome 19 locus apolipoprotein C-II association with multiple sclerosis.

PMID- 10962552
TI  - The activation loop in Lck regulates oncogenic potential by inhibiting basal
      kinase activity and restricting substrate specificity.
AB  - The activities of Src-family non-receptor tyrosine kinases are regulated by
      structural changes that alter the orientation of key residues within the
      catalytic domain. In this study, we investigate the effects of activation loop
      mutations on regulation of the lymphocyte-specific kinase Lck (p56lck).
      Substitution of 5 - 7 residues amino terminal to the conserved activation loop
      tyrosine (Y394) increases kinase activity and oncogenic potential regardless of
      regulatory C-terminal tail phosphorylation levels (Y505), while most mutations in
      the 13 residues carboxyl to Y394 decrease kinase activity. Phosphorylation of the
      C-terminal regulatory tail is carried out by the cytosolic tyrosine kinase Csk
      and we find that mutations upstream or downstream of Y394 or mutation of Y394 do
      not affect the level of Y505 phosphorylation. In addition, we report that
      mutations on either side of Y394 affect substrate specificity in vivo. We
      conclude that the high degree of conservation across the entire activation loop
      of Src-family kinases is critical for normal regulation of kinase activity and
      oncogenicity as well as substrate selection. Oncogene (2000) 19, 3961 - 3961.

PMID- 10962553
TI  - The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell size and
      survival in Drosophila.
AB  - Akt (or PKB) is an oncogene involved in the regulation of cell survival. Akt is
      regulated by phosphatidylinositol 3-OH kinase (PI3'K) signaling and has shown to
      be hyperactivated through the loss of the PTEN tumor suppressor. In Drosophila,
      insulin signaling as studied using the Drosophila IRS-4 homolog (Chico) has been
      shown to be a crucial regulator of cell size. We have studied Drosophila Akt
      (Dakt1) and have shown that it is also involved in the regulation of cell size.
      Furthermore we have performed genetic epistasis tests to demonstrate that in
      Drosophila, PI3'K, PTEN and Akt comprise a signaling cassette that is utilized
      during multiple stages of development. In addition, we show that this signaling
      cassette is also involved in the regulation of cell survival during
      embryogenesis. This study therefore establishes the evolutionary conservation of
      this signaling pathway in Drosophila. Oncogene (2000) 19, 3971 - 3977.

PMID- 10962554
TI  - Isolation and characterization of sixteen novel p53 response genes.
AB  - The EB-1 cell line is a stable transfectant of EB, a p53 null colon carcinoma
      cell line, with an inducible promoter controlling expression of a wild type p53
      cDNA. The induced p53 is transcriptionally active and gives rise to apoptosis in
      these cells. Using this cellular model for presence or absence of the
      transcription factor p53 and transactivated genes, the Suppression Subtractive
      Hybridization (SSH) technique permitted the isolation of 17 mRNA candidates (GIPs
      Genes induced by p53), whose expression appears to be p53-dependent. Identity has
      been established for nine of the 17 isolated candidates. These are HGFL/MSP, Zap
      70, APOBEC2, Ponsin/SH3P12/CAP/FLAF2, CDCrel2b/H5/Pnutl2, IgG, lats 2,
      cytokeratin 15 and PIG-3 (quinone oxidoreductase). The latter gene is the only
      GIP previously demonstrated to be p53 regulated. Of the eight remaining GIPs, six
      correspond to Unigene clusters. One candidate, GIP #1, is significantly
      homologous (72% identity) to a chicken zinc finger protein, CTCF, which binds to
      insulator elements and thus attenuates enhancer cross-talk between physically
      adjacent promoters. The p53-dependent expression of GIPs was confirmed by
      dependence of expression upon induction of wt p53 expression in the EB-1 cellular
      model and by up-regulation following activation of an endogenous wt p53 by
      treatment with adriamycin. Oncogene (2000) 19, 3978 - 3987.

PMID- 10962555
TI  - Influence of the human endogenous retrovirus-like element HERV-E.PTN on the
      expression of growth factor pleiotrophin: a critical role of a retroviral Sp1
      binding site.
AB  - Germ line insertion of a human endogenous retrovirus-like element (HERV-E.PTN)
      into the growth factor pleiotrophin (PTN) gene generated a phylogenetically new
      promoter driving the expression of functional HERV-PTN fusion transcripts. Here
      we show by in situ hybridization, that HERV-PTN fusion transcripts are expressed
      in malignant trophoblasts (i.e. choriocarcinoma) and in the proliferative and in
      the invasive trophoblasts of gestational trophoblastic tissue. Additionally, a
      1.9 kb fragment of the HERV-derived PTN promoter was analysed which has strong
      activity when transiently transfected into choriocarcinoma JEG-3 cells in
      contrast to HeLa cells. Deletion of the retrovirally-derived promoter portion
      abolished its activity and an enhancer (+443 to +486) was identified in this
      region. Electrophoretic mobility shift and supershift experiments identified a
      Sp1 binding site in this enhancer and site specific mutation of this site
      abolished its activity in choriocarcinoma cells. Sp1 overexpression in Drosophila
      SL2 cells showed that the enhancer activity is mediated via Sp1 binding in vivo.
      Furthermore, mutation of the Sp1 binding site reduced the activity of a promoter
      test fragment in choriocarcinoma cells by 80%. Our result shows that a retroviral
      Sp1 binding site in the PTN promoter is important for the expression of growth
      factor pleiotrophin in human choriocarcinoma cells. Oncogene (2000) 19, 3988 -
      3998.

PMID- 10962556
TI  - Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and
      glioblastoma phenotype by signal-regulatory proteins (SIRPs).
AB  - Several growth factors and cytokines, including EGF, are known to induce tyrosine
      phosphorylation of Signal Regulatory Proteins (SIRPs). Consistent with the idea
      that increased phosphorylation activates SIRP function, we overexpressed human
      SIRPalpha1 in U87MG glioblastoma cells in order to examine how SIRPalpha1
      modulates EGFR signaling pathways. Endogenous EGFR proteins are overexpressed in
      U87MG cells and these cells exhibit survival and motility phenotypes that are
      influenced by EGFR kinase activity. Overexpression of the SIRPalpha1 cDNA
      diminished EGF-induced phosphoinositide-3-OH kinase (PI3-K) activation in U87MG
      cells. Reduced EGF-stimulated activation of PI3-K was mediated by interactions
      between carboxyl terminus of SIRPalpha1 and the Src homology-2 (SH2)-containing
      phosphotyrosine phosphatase, SHP2. SIRPalpha1 overexpression also reduced the EGF
      induced association between SHP2 and the p85 regulatory subunit of PI3-K.
      Inhibition of transformation and enhanced apoptosis following gamma-irradiation
      were observed in SIRPalpha1-overexpressing U87MG cells, and enhanced apoptosis
      was associated with reduced levels of bcl-xL protein. Furthermore, SIRPalpha1
      overexpressing U87MG cells displayed reduced cell migration and cell spreading
      that was mediated by association between SIRPalpha1 and SHP2. However, SIRPalpha1
      overexpressing U87MG clonal derivatives exhibited no differences in cell growth
      or levels of mitogen-activated protein kinase (MAPK) activation. These data
      reveal a pathway that negatively regulates EGFR-induced PI3-K activation in
      glioblastoma cells and involves interactions between SHP2 and tyrosine
      phosphorylated SIRPalpha1. These results also suggest that negative regulation of
      PI3-K pathway activation by the SIRP family of transmembrane receptors may
      diminish EGFR-mediated motility and survival phenotypes that contribute to
      transformation of glioblastoma cells. Oncogene (2000) 19, 3999 - 4010.

PMID- 10962557
TI  - High levels of phosphorylated c-Jun, Fra-1, Fra-2 and ATF-2 proteins correlate
      with malignant phenotypes in the multistage mouse skin carcinogenesis model.
AB  - Analysis of the functions of AP-1 transcription factor in cellular systems has
      shown its key role as a mediator of oncogenic signals. The employment of suitable
      animal model systems greatly facilitates the study of changes in the composition
      and activity of the AP-1 complex. Here, we have analysed the quantitative and
      qualitative changes of AP-1 at different stages of carcinogenesis in mouse skin
      cell lines, derived from tumours induced by chemical mutagens. The findings of
      this study suggest that elevated AP-1 DNA binding and transactivation activity
      characterize the carcinoma cell lines, most notably the highly malignant spindle
      carcinomas. In addition, increased amounts and post-translational modifications
      of c-Jun, Fra-1, Fra-2 and ATF-2 proteins account for a high percentage of the
      increased AP-1 activity. Remarkably, high levels of phosphorylated ATF-2 protein
      were detected in malignant cell lines, indicating a novel role of ATF-2 in tumour
      progression. c-Jun and ATF-2 proteins are phosphorylated by highly active JNK
      kinases present in tumour cells. Finally, our results indicate distinct functions
      for different AP-1 components in the promotion and progression of mouse skin
      tumours. Oncogene (2000) 19, 4011 - 4021.

PMID- 10962558
TI  - Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2delta, an
      immunoglobulin-like cell adhesion molecule at adherens junctions.
AB  - We have recently found a novel functional unit of cell-cell adhesion at cadherin
      based adherens junctions, consisting of at least nectin, an immunoglobulin-like
      cell adhesion molecule, and afadin, an actin filament-binding protein which
      connects nectin to the actin cytoskeleton. Among the members of the nectin
      family, we have found here that nectin-2delta is tyrosine-phosphorylated in
      response to cell-cell adhesion. Expression of E-cadherin induced tyrosine
      phosphorylation of nectin-2delta, while disruption of cell-cell adhesion by an
      anti-E-cadherin antibody reduced the tyrosine phosphorylation of nectin-2delta.
      An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine
      phosphorylation of nectin-2delta. In addition, Src kinase tyrosine phosphorylates
      the recombinant cytoplasmic region of nectin-2delta in vitro. The major tyrosine
      phosphorylation site of nectin-2delta was Tyr505 in the cytoplasmic region,
      because the mutant nectin-2delta, of which Tyr505 was replaced by Phe, showed a
      loss of tyrosine phosphorylation in vivo and in vitro. These results, together
      with our recent observations, indicate that the cadherin-catenin system and the
      nectin-afadin system are closely connected to each other. The cadherin-mediated
      cell-cell adhesion system may link to the activation of a Src family kinase, that
      is, at least in part, responsible for the tyrosine phosphorylation of the
      cytoplasmic region of nectin-2delta. Oncogene (2000) 19, 4022 - 4028.

PMID- 10962559
TI  - Quantitative determination of Rap 1 activation in cyclic nucleotide-treated HL-60
      leukemic cells: lack of Rap 1 activation in variant cells.
AB  - We have previously isolated variant HL-60 cells that are resistant to cGMP
      induced differentiation and showed that they are deficient in proteolytic
      cleavage and/or carboxyl methylation of Rap 1A (J. Biol. Chem. 269, 32155 -
      32161, 1994 and Oncogene 17, 2211 - 2233, 1998). We have now developed an enzyme
      based method for assessing Rap 1 activation which is quantitative and provides a
      measurement of the per cent of Rap molecules in the active GTP-bound state. Using
      this method, we show that cAMP and cGMP analogs activate Rap 1 in parental HL-60
      cells but not in the variant cells and that H-89, a cAMP-dependent protein kinase
      inhibitor, has no effect on cAMP-induced Rap 1 activation in parental cells.
      Thus, cAMP activation of Rap 1 in HL-60 cells is likely through a cAMP-regulated
      guanine nucleotide exchange factor (cAMP-GEF) and since cAMP does not activate
      Rap 1 in the variant cells, the data suggest that full post-translational
      processing of Rap 1 is necessary for cAMP-GEF activation of Rap 1. Activation of
      Rap 1 by cGMP analogs has not been previously found and suggests possible cross
      talk between the NO/cGMP signal transduction pathway and Rap 1 signaling.
      Oncogene (2000) 19, 4029 - 4034.

PMID- 10962561
TI  - Conformational phenotype of p53 is linked to nuclear translocation.
AB  - P53 is inactivated in tumors by mechanisms other than mutations in the p53 gene
      itself. To gain insight into the mechanisms by which this inactivation occurs, we
      chemically mutagenized A1-5 cells expressing high levels of temperature sensitive
      p53val135 (tsp53) and selected for clones that were capable of growth at the
      permissive temperature for p53 activation. We expanded 22 clones (ALTR cells for
      A1-5 Low Temperature Resistant) that could grow at the permissive temperature.
      Most exhibited cytoplasmic sequestration as the mechanism by which p53 was
      inactivated. We show here that this cytoplasmically sequestered tsp53 protein is
      maintained in a mutant conformation. Only in clones with nuclear localized p53 is
      it also expressed in the wild-type conformation suggesting that subcellular
      localization of tsp53 is important in determining the conformation of the
      protein. Consistent with this, we show that the changes in conformation of p53 in
      A1-5 and SK-N-SH cells induced by ionizing radiation also correlate with nuclear
      translocation of p53. We suggest that nuclear translocation of p53 can result in
      a change in the conformation from mutant to wild-type but that these may be two
      separable events. Oncogene (2000) 19, 4042 - 4049.

PMID- 10962560
TI  - pRb and Cdk regulation by N-(4-hydroxyphenyl)retinamide.
AB  - The cancer chemopreventive synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR)
      can inhibit the growth and induce apoptosis of tumor cells. In this study we
      analysed the growth suppressive effect of HPR on human breast cancer cell lines
      in vitro and the role of the retinoblastoma protein (pRb) in this response.
      Treatment of MCF7, T47D and SKBR3 for 24 - 48 h with 3 microM HPR, a
      concentration attainable in vivo, resulted in growth inhibition and marked
      dephosphorylation of pRb involving Ser612, Thr821, Ser795 and Ser780, target
      residues for cyclin-dependent kinase 2 (Cdk2) the former two, and Cdk4 the latter
      two. Interestingly, this dephosphorylation of pRb occurred in S-G2-M phase cells,
      as revealed by experiments on cells fractionated by FACS according to the cell
      cycle phase, hence suggesting that the retinoid interferes with the regulation of
      pRb phosphorylation. The in vitro phosphorylation of a GST-pRb recombinant
      substrate by Cdk2 immunocomplexes from MCF7, T47D and SKBR3 was markedly
      suppressed after HPR treatment, whereas that by Cdk4 complexes was suppressed in
      T47D and SKBR3 but not in MCF7. The steady-state levels of Cdk2, Cdk4 and Cyclin
      A proteins were unaffected by HPR, while those of Cyclin D1 were significantly
      reduced in all three cell lines. Interestingly, Cyclin D1 downregulation by HPR
      correlated with transcriptional repression, but not with enhanced proteolysis of
      Cyclin D1 typically elicited by other retinoids. Collectively, our data suggest
      that the antiproliferative activity of HPR arises from its capacity to maintain
      pRb in a de-phosphorylated growth-suppressive status in S-G2/M, possibly through
      Cyclin D1 downregulation and inhibition of pRb-targeting Cdks. Oncogene (2000)
      19, 4035 - 41.

PMID- 10962562
TI  - BRCA1 activation of the GADD45 promoter.
AB  - Breast cancer susceptibility gene BRCA1 has been implicated in the control of
      gene regulation and such regulated genes are thought to mediate the biological
      role of BRCA1. Overexpression of BRCA1 induces GADD45, a p53-regulated and stress
      inducible gene. However, the molecular mechanism by which BRCA1 induces the
      expression GADD45 remains unclear. In this report, we have shown that the GADD45
      promoter is strongly activated following expression of wild-type BRCA1. In
      contrast, both the tumor-derived BRCA1 mutants (p1749R and Y1853insA) and
      truncated BRCA1 mutant protein (Delta500 - 1863 BRCA1), which lack
      transactivation activity, were unable to activate the GADD45 promoter, indicating
      that the BRCA1-mediated activation of the GADD45 promoter requires normal
      transcriptional properties of BRCA1. BRCA1 did not induce the c-Jun and c-fos
      promoters, which rules out a general effect of BRCA1 on other immediate
      responsive genes. Expression of the human papillomavirus E6 and the dominant
      negative mutant p53 proteins had no effect on the induction of the GADD45
      promoter by BRCA1, suggesting that activation of the GADD45 promoter by BRCA1 is
      independent of cellular p53 function. With the 5'-deletion analysis, the BRCA1
      responsive element of the GADD45 promoter was mapped at the region from -121 to 
      75. Disruption of this region resulted in the abrogation of BRCA1 activation of
      the GADD45 promoter. Taken together, these results demonstrate that the mechanism
      by which BRCA1 induces GADD45 is mainly through the transactivation of the GADD45
      promoter, further demonstrating the evidence that GADD45 acts as one of the BRCA1
      regulated genes. Oncogene (2000) 19, 4050 - 4057.

PMID- 10962563
TI  - The proto-oncogene c-Cbl is a positive regulator of Met-induced MAP kinase
      activation: a role for the adaptor protein Crk.
AB  - Hepatocyte growth factor triggers a complex biological program leading to
      invasive cell growth by activating the c-Met receptor tyrosine kinase. Following
      activation, Met signaling is elicited via its interactions with SH2-containing
      proteins, or via the phosphorylation of the docking protein Gab1, and the
      subsequent interaction of Gab1 with additional SH2-containing effector molecules.
      We have previously shown that the interaction between phosphorylated Gab1 and the
      adaptor protein Crk mediates activation of the JNK pathway downstream of Met. We
      report here that c-Cbl, which is a Gab1-like docking protein, also becomes
      tyrosine-phosphorylated in response to Met activation and serves as a docking
      molecule for various SH2-containing molecules, including Crk. We further show
      that Cbl is similarly capable of enhancing Met-induced JNK activation, and
      several lines of experimentation suggests that it does so by interacting with
      Crk. We also show that both Cbl and Gab1 enhance Met-induced activation of
      another MAP kinase cascade, the ERK pathway, in a Crk-independent manner. Taken
      together, our studies demonstrate a previously unidentified functional role for
      Cbl in Met signaling and suggest that Met utilizes at least two docking proteins,
      Gab1 and Cbl, to activate downstream signaling pathways. Oncogene (2000) 19, 4058
      - 4065.

PMID- 10962564
TI  - Methylation of conserved CpG sites neighboring the beta retinoic acid response
      element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast
      cancer cells.
AB  - We investigated the mechanism of retinoic acid receptor (RAR) beta2 gene
      silencing in breast cancer cells. Transfection experiments indicated that MCF-7
      cells transactivate an exogenous beta2 promoter (-1470/+156) to the same extent
      as MTSV1.7 breast epithelial cells, which express endogenous RARbeta2. This was
      true even in the context of replicated chromatin, suggesting a cis-acting rather
      than a trans-acting defect. Cytosine methylation, a cis-acting DNA modification,
      has been implicated in RARbeta2 silencing in cancer cells. Upon bisulfite genomic
      sequencing, we found that 3 CpG sites in the beta2 RARE region were variably
      methylated in MCF-7 cells but were not methylated in MTSV1.7 cells or in 2 MDA-MB
      231 subclones that differed in RARbeta2 expression (high in clone A2, low in
      clone A4). However, the 5'-UTR region was hypermethylated in clone A4 relative to
      clone A2 cells. Following 5-azacytidine treatment, RA and trichostatin A markedly
      induced RARbeta2 expression in MCF-7 cells but not in MDA-MB-231 clone A4 cells.
      A beta2 RARE reporter construct in which the methylation-susceptible cytosines in
      the sense strand were replaced by thymine displayed marked loss of activity in a
      replicated chromatin-dependent manner. We conclude that cytosine methylation
      contributes to RARbeta2 gene silencing in MCF-7 cells and that methylation of the
      RARE region may be particularly important. Oncogene (2000) 19, 4066 - 4070.

PMID- 10962565
TI  - General effect of Sam68 on Rev/Rex regulated expression of complex retroviruses.
AB  - We have previously demonstrated that overexpression of Sam68 functionally
      substitutes for, as well as synergizes with, HIV-1 Rev in RRE-mediated gene
      expression and virus replication. In addition, C-terminal deletion mutants of
      Sam68 exhibit a transdominant negative phenotype in HIV replication. We now
      report that Sam68 also enhances the activities of Rev-like proteins of other
      complex retroviruses (e.g. HTLV-1 and EIAV) on their respective RNA targets.
      Furthermore, we demonstrate that Sam68 can function alone as well as synergize
      with Rev-MS2 and/or Rex-MS2 chimeric proteins on expression mediated by the
      corresponding RRE-MS2 fusion RNA element. Additionally, dominant negative mutants
      of Sam68 also repressed the synergistic activation of Sam68 with Rex, E-Rev,
      and/or Rev-MS2/Rex-MS2 on their corresponding RNA targets. Thus, Sam68 may play
      an important role in the post-transcriptional regulation of all complex
      retroviruses. Oncogene (2000) 19, 4071 - 4074

PMID- 10962566
TI  - Germ cell-like telomeric length homeostasis in nonseminomatous testicular germ
      cell tumors.
AB  - Telomere maintenance plays an important role in cell proliferation and tumor
      survival. Human male germ cells, which carry long telomeres and express
      telomerase, give rise to a highly heterogeneous group of malignant tumors. We
      compared telomeric length and telomerase activity between two major histological
      types of primary testicular germ cell tumors. Fifteen out of 16 seminoma samples
      revealed telomeric restriction fragment (TRF) length below 13 kb; the remaining
      seminoma showed a major TRF fraction of 18 kb and a distinct minor fraction of
      above 23 kb length. In contrast, all 13 samples from nonseminomas showed TRF
      length >/=23 kb, which is similar to that reported in human sperm. Nine out of 11
      seminoma specimens and six out of seven nonseminomas studied showed moderate to
      high telomerase activity, the only telomerase-negative nonseminoma being pure
      mature teratoma. These results indicate to a major difference in telomeric length
      between seminomas and nonseminomas, which is apparently unrelated to the presence
      of telomerase activity, and suggest a germline-like homeostasis of telomeric
      length is preserved in human nonseminomas. Oncogene (2000) 19, 4075 - 4078.

PMID- 10962567
TI  - Chromosomal instability and p53 inactivation are required for genesis of
      glioblastoma but not for colorectal cancer in patients with germline mismatch
      repair gene mutation.
AB  - We have previously reported high-frequency microsatellite instability (MSI-H) and
      germ-line mismatch repair gene mutation in patients with unusually young onset of
      high-grade glioma. Some of these patients developed metachronous MSI-H colorectal
      cancer and conformed to the diagnosis of Turcot's syndrome. Frameshift mutation
      of TGFbetaRII was present in all the colorectal carcinomas but not in brain
      tumours. We further characterized the genetic pathways of tumour evolution in
      these metachronous gliomas and colorectal carcinomas. All MSI-H glioblastomas had
      inactivation of both alleles of the p53 gene and showed over-expression of the
      p53 protein while none of the colorectal carcinomas had p53 mutation or protein
      over-expression. Flow cytometry and comparative genomic hybridization revealed
      that all glioblastomas were chromosomal unstable with aneuploid DNA content, and
      with a variable number of chromosomal arm aberrations. In contrast, the
      colorectal carcinomas had diploid or near-diploid DNA content with few
      chromosomal arm aberrations. The pattern of chromosomal aberrations in the two
      organs was different. Loss of 9p was consistently observed in all glioblastomas
      but not in colorectal carcinomas. Epidermal growth factor receptor amplification
      was absent in all glioblastomas and colorectal carcinomas. Our results suggest
      that both the frequency of p53 mutation and its effects differ greatly in the two
      organs. Following loss of mismatch repair function, p53 inactivation and
      chromosomal instability are not necessary for development of colorectal
      carcinoma, but are required for genesis of glioblastoma. Oncogene (2000) 19, 4079
      - 4083.

PMID- 10962568
TI  - Gene replacement with the human BRCA1 locus: tissue specific expression and
      rescue of embryonic lethality in mice.
AB  - We have generated transgenic mice that harbor a 140 kb genomic fragment of the
      human BRCA1 locus (TgN x BRCA1GEN). We find that the transgene directs
      appropriate expression of human BRCA1 transcripts in multiple mouse tissues, and
      that human BRCA1 protein is expressed and stabilized following exposure to DNA
      damage. Such mice are completely normal, with no overt signs of BRCA1 toxicity
      commonly observed when BRCA1 is expressed from heterologous promoters. Most
      importantly, however, the transgene rescues the otherwise lethal phenotype
      associated with the targeted hypomorphic allele (Brca1DeltaexllSA). Brca1-/-; TgN
      x BRCA1GEN bigenic animals develop normally and can be maintained as a distinct
      line. These results show that a 140 kb fragment of chromosome 17 contains all
      elements necessary for the correct expression, localization, and function of the
      BRCA1 protein. Further, the model provides evidence that function and regulation
      of the human BRCA1 gene can be studied and manipulated in a genetically tractable
      mammalian system. Oncogene (2000) 19, 4085 - 4090

PMID- 10962569
TI  - Expression of PTEN in PTEN-deficient multiple myeloma cells abolishes tumor
      growth in vivo.
AB  - Biochemical abnormalities associated with the development of multiple myeloma
      have been difficult to define especially in terms of demonstrating an in vivo
      effect of suspected lesions. Herein, we have identified such a defect associated
      with lack of expression of PTEN, a cellular phosphatase involved in the
      regulation of phosphatidylinositol phosphates (PIP's). In myeloma cells, PIP's
      are required for phosphorylation of Akt, a key event leading to inhibition of
      apoptosis. Loss of PTEN results in a failure to de-phosphorylate PIP's and a
      corresponding increase in Akt phosphorylation. OPM-2 cells lacking PTEN
      expression have the highest level of Akt phosphorylation of eight lines examined.
      Loss of PTEN was found to be associated with a 630 bp deletion corresponding to
      amino acids 56 - 267. Ectopic expression of wild type PTEN in OPM-2 cells
      inhibited Akt phosphorylation which was correlated with an increase in apoptosis.
      The in vivo relevance of loss of PTEN expression was demonstrated by injecting
      control and wild type PTEN transfected OPM-2 cells into SCID mice. Tumors arose
      at an incidence of 100% in controls, but only 50% (and of smaller size and longer
      latency) in low PTEN expressing clones. Importantly, clones expressing high
      levels of PTEN failed to produce tumors even at five times the latency period of
      controls. These results demonstrate that PTEN deletion/mutation is responsible
      for in vivo growth of this tumor and suggests that PTEN regulation may play an
      important role in tumor development in a subset of multiple myeloma patients.
      Oncogene (2000) 19, 4091 - 4095

PMID- 10962570
TI  - Characterization of distinct consecutive phases in non-genotoxic p53-induced
      apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8.
AB  - To dissect the p53-dependent apoptotic pathway, events following induction of
      temperature sensitive (ts) p53val138 were studied in a Ewing tumor cell line.
      Transcriptional deregulation of p53 targets first observable after 1 h at 32
      degrees C preceded activation of caspases and the break-down of mitochondrial
      respiratory activity. Activation of caspases was first observed 4 h after p53
      induction. Using peptide inhibitors we identified activation of caspase 8
      upstream of caspases-9 and -3. Although the caspase 8 specific inhibitor z
      IETD.fmk did not affect translocation of BAX to the mitochondrial membrane and
      cytochrome C release it almost completely blocked cleavage of the prototype
      caspase substrate PARP and DNA fragmentation while enforcing mitochondrial
      depolarization and production of reactive oxygene species (ROS). Activation of
      caspase 8 did not involve death-domain receptor signaling. Expression of BCL2
      only partially suppressed caspase activation but blocked apoptosis. Replacement
      of the N-terminus of p53val138 by the related VP16 transactivation domain created
      a ts p53 with a tanscriptional activity indistinguishable from p53val138 until
      the time of caspase activation. However, the VP16 - p53 fusion failed to trigger
      caspases and subsequent induction of the ROS producing gene pig3 paralleled by
      complete loss of apoptotic activity. These results indicate that p53-dependent
      transcriptional deregulation, triggering of the caspase cascade and the
      mitochondrial break-down occur in a timely ordered sequence coordinated by the
      genuine p53 amino terminus and suggest caspase 8 and PIG3 as key regulatory
      elements in this process. Oncogene (2000) 19, 4096 - 4107

PMID- 10962571
TI  - Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following
      induction and stabilization of the apoptotic effector Bak.
AB  - We demonstrate that treatment of HCW-2 cells, an apoptotic resistant variant of
      the human HL-60 promyelocytic leukemia cell line with phorbol-12-myristate
      acetate (PMA), induced differentiation along the monocytic lineage. During this
      process there was a dramatic increase in the mitochondrial levels of the
      apoptosis effector, Bak, due to the stabilization of bak mRNA, which was
      correlated with the sensitization of HCW-2 cells to respond to the apoptotic
      effect of staurosporine (STS). Treatment of PMA-differentiated, but not
      undifferentiated, HCW-2 cells induced processing of Bid, substantial efflux of
      cytochrome c from mitochondria to the cytosol, activation of caspase-3 and
      apoptosis. The biological significance of the increased mitochondrial Bak in
      differentiated HCW-2 cells was supported by the finding that transient
      transfection of a bak cDNA into HCW-2 cells conferred sensitivity to STS
      triggered apoptosis, as determined by pro-caspase-3 processing, cytochrome c
      efflux and DNA fragmentation. Our results suggest that the induction of Bak, upon
      monocytic differentiation, may be a critical event that regulates the apoptotic
      sensitivity of differentiated HCW-2 cells. Oncogene (2000) 19, 4108 - 4116

PMID- 10962572
TI  - Progressive changes in the leukemogenic signaling in BCR/ABL-transformed cells.
AB  - Our previous study indicated that BCR/ABL SH2 domain and BCR/ABL SH3 domain+SH2
      domain complex are required for immediate activation of the phosphatidylinositol
      3 kinase PI-3k)--> Akt serine/threonine kinase pathway and of the signal
      transducer and activator of transcription 5 (STAT5), respectively, in
      hematopoietic cells. We show here that the defect in activation of PI-3k/Akt by
      BCR/ABL DeltaSH2 mutant (SH2 domain deleted) and of STAT5 by BCR/ABL
      DeltaSH3+DeltaSH2 mutant (SH3 and SH2 domains deleted) is not permanent and both
      Akt and STAT5 could be 're-activated' by in vitro culture. This phenomenon was
      responsible for increased resistance to apoptosis, growth factor-independent
      proliferation and leukemogenesis in SCID mice. Incubation of cells with BCR/ABL
      tyrosine kinase inhibitor STI571 abrogated the 're-activation' of Akt or STAT5 by
      BCR/ABL SH3+SH2 mutants in some clones, in the others Akt and STAT5 activation
      became independent on BCR/ABL kinase activity. The immediate upstream activators
      of Akt and STAT5 such as PI-3k and Jak-2 were also activated. In addition, the
      common beta subunit of IL-3/IL-5/GM-CSF receptor was tyrosine phosphorylated in
      the clones in which 're-activation' was dependent on the BCR/ABL kinase activity.
      These results suggested that 're-activation' of Akt and STAT5, in the absence of
      functional BCR/ABL SH3+SH2 domains, may be achieved by two different mechanisms:
      (i) BCR/ABL kinase-dependent activation of alternative pathway(s) and (ii)
      additional genetic changes stimulating Akt and STAT5 independently of BCR/ABL.
      Oncogene (2000) 19, 4117 - 4124

PMID- 10962573
TI  - Gene expression profiling of human colon cancer cells following inhibition of
      signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of
      the hsp90 molecular chaperone.
AB  - A number of molecular therapeutic agents, derived from exploiting our knowledge
      of the oncogenic pathways that are frequently deregulated in cancer, are now
      entering clinical trials. One of these is the novel agent 17-allylamino-17
      demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone.
      Treatment of four human colon cancer cell lines with iso-effective concentrations
      of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal
      transduction. We have used gene expression array analysis to identify genes
      responsive to treatment with this drug. The expression of hsp90 client protein
      genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and
      caveolin-1 were deregulated following treatment. These observations were
      consistent with inhibition of signal transduction and suggested a possible
      mechanism of resistance or recovery from 17-allylamino-17-demethoxygeldanamycin
      treatment. The results shed light on the molecular mode of action of the hsp90
      inhibitors, and suggest possible molecular markers of drug action for use in
      hypothesis testing clinical trials. Oncogene (2000) 19, 4125 - 4133

PMID- 10962574
TI  - Blockade of Smad4 in transformed keratinocytes containing a Ras oncogene leads to
      hyperactivation of the Ras-dependent Erk signalling pathway associated with
      progression to undifferentiated carcinomas.
AB  - Smad4 functions as a transcription factor in TGF-beta signalling. We have
      investigated the role of Smad4 in the TGF-beta1 cell responses of transformed PDV
      keratinocytes, which contain a Ras oncogene, and of non-tumorigenic MCA3D
      keratinocytes, by transfecting both cell lines with a dominant-negative Smad4
      construct. Smad4 mediates TGF-beta1-induced up-regulation of p21Cip1 and growth
      arrest in MCA3D cells. However, in PDV keratinocytes, Smad4 is only partially
      involved in TGF-beta1-induced growth inhibition, and does not mediate enhancement
      of p21Cip1 levels by the growth factor. TGF-beta1 activates Ras/Erk signalling
      activity in both cell lines. PD098059, a specific inhibitor of MEK, disminishes
      TGF-beta1-induced p21Cip1 levels in PDV but not in MCA3D cells, suggesting an
      involvement of Erk in up-regulation of p21Cip1 by TGF-beta1 in PDV cells. PDV
      dominant-negative Smad4 cell transfectants, but not MCA3D transfectants, showed
      constitutive hyperactivation of the Ras/Erk signalling pathway, increased
      secretion of urokinase, higher motility properties, and a change to a
      fibroblastoid cell morphology associated in vivo with the transition from a well
      differentiated to a poorly differentiated tumour phenotype. Infection of MCA3D
      control and dominant negative Smad4 cell transfectants with retroviruses carrying
      a Ras oncogene led to enhanced p21Cip1 and urokinase secreted levels,
      independently of TGF-beta1 stimulation, that were reduced by PD098059. These
      results suggest that Smad4 acts inhibiting Ras-dependent Erk signalling activity
      in Ras-transformed keratinocytes. Loss of Smad4 function in these cells results
      in hyperactivation of Erk signalling and progression to undifferentiated
      carcinomas. Oncogene (2000) 19, 4134 - 4145

PMID- 10962575
TI  - Lack of p19INK4d in human testicular germ-cell tumours contrasts with high
      expression during normal spermatogenesis.
AB  - p19INK4d, a member of the INK4 family of cyclin-dependent kinase inhibitors,
      negatively regulates the proto-oncogenic cyclin D/CDK4(6) complexes whose ability
      to phosphorylate the retinoblastoma tumour suppressor (RB) promotes G1/S
      transition. In contrast to the related p16INK4a tumour suppressor, expression
      patterns of 19INK4d in human tissues and tumours remain unknown. As the RB
      pathway is commonly targeted in cancer, and mouse models suggest a role for
      p19INK4d in spermatogenesis, we examined the abundance and localization of
      p19INK4d in the human testis, both during normal development and at various
      stages of germ-cell tumour pathogenesis. Our data show that the p19INK4d protein
      is abundant in spermatocytes of normal human adult testes, whereas virtually no
      p19INK4d is detectable in testicular cancer, including the preinvasive carcinoma
      in situ stage. Together with the lack of p19INK4d in human foetal germ cells,
      these results support the concept of foetal origin of the testicular germ-cell
      tumours, and help better understand the emerging role of the RB pathway in
      spermatogenesis and tumorigenesis in the human testis. Oncogene (2000) 19, 4146 -
      4150

PMID- 10962576
TI  - The Bmx tyrosine kinase is activated by IL-3 and G-CSF in a PI-3K dependent
      manner.
AB  - Cytoplasmic protein tyrosine kinases play crucial roles in signaling via a
      variety of cell surface receptors. The Bmx tyrosine kinase, a member of the Tec
      family, is expressed in hematopoietic cells of the granulocytic and monocytic
      lineages. Here we show that Bmx is catalytically activated by interleukin-3 (IL
      3) and granulocyte-colony stimulating factor (G-CSF) receptors. Activation of Bmx
      required phosphatidylinositol 3-kinase (PI-3K) as demonstrated by the ability of
      PI-3K inhibitors to block the activation signal. A green fluorescent protein
      (GFP) tagged Bmx was translocated to cellular membranes upon co-expression of a
      constitutively active form of PI-3K, further indicating a role for PI-3K in
      signaling upstream of Bmx. The expression of wild type Bmx in 32D myeloid
      progenitor cells resulted in apoptosis in the presence of G-CSF, while cells
      expressing a kinase dead mutant of Bmx differentiated into mature granulocytes.
      However, Bmx did not modulate IL-3-dependent proliferation of the cells. These
      results demonstrate distinct effects of Bmx in cytokine induced proliferation and
      differentiation of myeloid cells, and suggest that the stage specific expression
      of Bmx is critical for the differentiation of myeloid cells. Oncogene (2000) 19,
      4151 - 4158

PMID- 10962577
TI  - Paclitaxel sensitivity of breast cancer cells with constitutively active NF
      kappaB is enhanced by IkappaBalpha super-repressor and parthenolide.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) regulates genes
      important for tumor invasion, metastasis and chemoresistance. Normally, NF-kappaB
      remains sequestered in an inactive state by cytoplasmic inhibitor-of-kappaB
      (IkappaB) proteins. NF-kappaB translocates to nucleus and activates gene
      expression upon exposure of cells to growth factors and cytokines. We and others
      have shown previously that NF-kappaB is constitutively active in a subset of
      breast cancers. In this study, we show that constitutive activation of NF-kappaB
      leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c
      IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells.
      Furthermore, expression of the anti-apoptotic tumor necrosis factor receptor
      associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated
      by NF-kappaB in certain breast cancer cells. We also demonstrate that NF-kappaB
      inducible genes protect cancer cells against paclitaxel as MDA-MB-231 breast
      cancer cells modified to overexpress IkappaBalpha required lower concentrations
      of paclitaxel to arrest at the G2/M phase of the cell cycle and undergo apoptosis
      when compared to parental cells. The effect of NF-kappaB on paclitaxel
      sensitivity appears to be specific to cancer cells because normal fibroblasts
      derived from embryos lacking p65 subunit of NF-kappaB and wild type littermate
      embryos were insensitive to paclitaxel-induced G2/M cell cycle arrest.
      Parthenolide, an active ingredient of herbal remedies such as feverfew (tanacetum
      parthenium), mimicked the effects of IkappaBalpha by inhibiting NF-kappaB DNA
      binding activity and Mn-SOD expression, and increasing paclitaxel-induced
      apoptosis of breast cancer cells. These results suggest that active ingredients
      of herbs with anti-inflammatory properties may be useful in increasing the
      sensitivity of cancers with constitutively active NF-kappaB to chemotherapeutic
      drugs. Oncogene (2000) 19, 4159 - 4169

PMID- 10962578
TI  - Absence of evidence for a familial breast cancer susceptibility gene at
      chromosome 8p12-p22.
AB  - Several recent studies indicate that the majority of families with five or fewer
      cases of breast cancer and no cases of ovarian cancer are not due to BRCA1 or
      BRCA2. It has been proposed that a further breast cancer susceptibility gene that
      may account for some of these families is located on chromosome 8p12-p22. We have
      identified 31 site-specific breast cancer families that have a greater than 80%
      posterior probability of being due to genes other than BRCA1 or BRCA2. These
      families have been examined for linkage to 8p12-p22 using markers flanking the
      putative location of the gene. The overall multi-point LOD score is strongly
      negative across the whole 44 cM. The individual multi-point LOD score is negative
      in 23 families and only exceeds 0.5 in a single family (with a multi-point LOD
      score of 1.22). The maximum heterogeneity LOD score was 0.03 at marker D8S136
      with estimated proportion linked (alpha) of 3% (95% CI 0 - 30%). These data do
      not lend support to the hypothesis that chromosome 8p12-p22 harbours a familial
      breast cancer susceptibility gene. Oncogene (2000) 19, 4170 - 4173

PMID- 10962579
TI  - Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases
      resistance to radiation induced cell death.
AB  - Inhibitory regulators of apoptosis play a critical role in the responsiveness of
      tumour cells to cytotoxic agents. The X-linked inhibitor of apoptosis protein
      (XIAP) is a member of a novel family of Inhibitor of Apoptosis (IAP) proteins.
      Here we show that acute low dose ionizing irradiation results in the
      translational upregulation of XIAP that correlates with an increased resistance
      to radiation in non-small cell lung carcinoma. This upregulation is mediated by
      an internal ribosome binding mechanism via an IRES element located within a XIAP
      5' UTR. Transient overexpression of XIAP rendered human carcinoma cells resistant
      to low dose gamma-irradiation. By contrast, the antisense targeting of XIAP
      resulted in increased cell death following irradiation advocating a distinct role
      for XIAP in radiation resistant phenotype of human cancers. Oncogene (2000) 19,
      4174 - 4177

PMID- 10962580
TI  - Identification of genomic DNA sequences bound by mutant p53 protein (Gly245-
      >Ser) in vivo.
AB  - Mutant p53 proteins were shown to exert complex DNA-interactions in vitro, like
      binding to MAR-DNA, but so far it is unknown whether such interactions also occur
      in vivo. Therefore we analysed the binding of mutant (mut) p53 (Gly245-->Ser) in
      Onda 11 glioma cells to cellular DNA in vivo, using p53-specific chromatin
      immunoprecipitation (CHIP) after in vivo cross-linking of mut p53 to genomic DNA
      with cisplatin. We identified genomic DNA fragments to which mut p53 (Gly245-
      >Ser) could be cross-linked in vivo. Purified recombinant mut p53 (Gly245-->Ser)
      was able to bind specifically to such elements in PCR-EMSA in vitro, supporting
      the idea that this mut p53 protein interacts with genomic DNA in vivo. The
      genomic DNA fragments identified are vastly different in sequence, but display as
      a common feature a high likelihood to adopt a non B-DNA conformation. Therefore
      we propose that structural determinants within these DNA elements are important
      for their interaction with mut p53 (Gly245-->Ser) in vivo. Oncogene (2000) 19,
      4178 - 4183

PMID- 10962582
TI  - Prophets of doom or profits for boom?

PMID- 10962581
TI  - Cdk2 associates with MAP kinase in vivo and its nuclear translocation is
      dependent on MAP kinase activation in IL-2-dependent Kit 225 T lymphocytes.
AB  - Cell proliferation is controlled by cdk2 which in association with cyclin E and A
      regulates G1/S transition and S phase progression. cdk2 activation is dependent
      on its localization in the nucleus where regulatory mediators are found. We
      report that activation of cdk2 is associated with the formation of cdk2/MAP
      Kinase complexes. cdk2 associates with both inactive and activated MAP Kinase.
      Prevention of MAP Kinase activation by the MEK inhibitor PD98059 inhibits both
      activation and nuclear localization of cdk2 and S phase entry. These findings
      indicate that the nuclear translocation of cdk2 is associated with the formation
      of molecular complexes containing active MAP Kinase and is dependent on MAP
      Kinase activation. Oncogene (2000) 19, 4184 - 4189

PMID- 10962583
TI  - Why the government was right to change the 'Our Healthier Nation' accidental
      injury target.
AB  - We congratulate the current UK Government on their inclusion of accidental injury
      as one of the national targets in the White Paper: Saving Lives-Our Healthier
      Nation (OHN). We had concerns about the particular target that was proposed in
      the Green Paper: 'ellipsisto reduce the rate of accidents-here being defined as
      those which involve a hospital visit or consultation with a family doctor-by at
      least a fifthellipsis'. The limitations of this target were: firstly, it would
      focus attention on minor injury and so not reflect the main burden of injury; and
      secondly, that ascertainment of cases would be influenced by social factors as
      well as provision of service and access factors. The new target stated in Saving
      Lives also has its limitations since it will be influenced by service factors.
      This target is to reduce by 10% the rate of serious injury, defined as injury
      resulting in four or more days in hospital. We have proposed the use of an
      alternative indicator of unintentional injury occurrence, based on serious long
      bone fracture admitted to the hospital. This alternative indicator is based on
      the occurrence of serious rather than minor injury. It is likely that a high
      proportion of cases of these injuries can be identified from existing data
      sources. Ascertainment of cases is likely to be independent of social, service or
      access factors. Finally, these injuries are associated with significant long term
      outcomes including disablement, reduced functional capacity and reduced quality
      of life. It does have the limitation that it does not measure all serious injury.
      Such a measure is much more difficult to achieve. Further improvements to our
      proposed indicator could be made in a number of ways, through investigating an
      extended definition of the indicator to include a range of other serious
      injuries, improving the quality of existing data, making other data sources
      available, including outpatient data, and making serious injury a notifiable
      disease.

PMID- 10962584
TI  - Possible immediate and long-term health effects following exposure to chemical
      warfare agents.
AB  - Agents of chemical warfare continue to pose a threat to human life.
      Organophosphorus compounds are possibly the best known and most used agents in
      recent times. These are known to produce acute ill health and death and, probably
      equally important, many diverse delayed effects, many of which are not clinically
      nor pathologically well defined. The immediate and delayed effects of
      organophosphorus compounds, in particular, and those of other known agents of
      chemical warfare, such as mustard gas, Lewisite, phosgene, cyanides and the newer
      crowd control agents, are reviewed. Environmental sequelae of these agents are
      gaining importance as probable causes of chronic ill health amongst those living
      in regions where these agents have been used. The need to study the pattern of
      disease in exposed populations is emphasised.

PMID- 10962586
TI  - The mandatory collection of data on ethnic group of inpatients: experience of NHS
      trusts in England in the first reporting years.
AB  - This paper reports the findings of a questionnaire survey of the experience of
      NHS trusts' mandatory collection and the use of ethnic group data of hospital
      inpatients in the South Thames Region, and the analysis of the ethnicity field in
      the Hospital Episode Statistics (HES) database for England. High levels of
      invalid ethnicity coding in hospital episode statistics, 44.0% (regional range 31
      76%) in 1996/97 and 62.9% (range 43-90%) in 1995/96, render the data unusable.
      Over a third of NHS trusts felt there were other ethnic group categories for
      which data should have been collected, especially a subdivision of the white
      group. Only one in five trusts found the collection of ethnic group data useful
      and almost nine-tenths of trusts had made no use of the data, all but one trust
      stating that collection had not influenced the way services were provided. High
      levels of incompleteness of ethnic coding and data of questionable quality make
      it impossible to interpret the relative access of the ethnic minority population
      to hospital services and such collection is, arguably, at variance with Caldicott
      guidelines on patient-identifiable information. A high political priority must be
      accorded to the operationalisation of mandatory collection in order to meet new
      government objectives on fair access to services.

PMID- 10962585
TI  - The impact of a catastrophic earthquake on morbidity rates for various illnesses.
AB  - It has been reported that some natural catastrophes increase morbidity rates for
      illness. In this study, we investigated the impact of the 1995 Hanshin-Awaji
      earthquake on morbidity rates for various illnesses by analysis for correlations
      between the extent of damage due to the earthquake and occurrences of various
      illnesses. We searched the medical records of 1948 patients hospitalized due to
      illness in 48 hospitals during the first 15 days after the earthquake. In each of
      14 affected areas, the hospital admission rate and estimated morbidity ratio for
      each illness were calculated. Destruction ratios were determined based upon the
      number of dwellings completely destroyed in each area. For total illnesses and
      each major illness, linear regression analyses were performed comparing hospital
      admission rates, estimated morbidity ratios, and destruction ratios. Hospital
      admission rates and estimated morbidity ratios among the 1948 patients were
      significantly correlated to destruction ratios. With pneumonia, dehydration,
      acute heart failure, asthmatic attack, and peptic ulcer, hospital admission rates
      and estimated morbidity ratios were significantly related to destruction ratios,
      while no significant correlations between estimated morbidity ratios and
      destruction ratios existed for cerebral vascular disease or ischemic heart
      disease. Peptic ulcer and pneumonia showed especially high correlation values
      (age- and sex-adjusted R2>0.7). The present study revealed a strong link between
      the extent of damage due to the catastrophic earthquake and an increase in
      morbidity rates for acute illnesses, especially peptic ulcer and pneumonia.

PMID- 10962587
TI  - Council tax valuation band as marker of deprivation and of general practice
      workload.
AB  - This study tests the hypothesis that Council Tax Valuation Banding (CTVB) is a
      measure both of UK socioeconomic status and of general practice workload. It is a
      retrospective cohort study based in a UK semi-rural general practice, North
      Wiltshire. The study group is a randomised selection of UK general practice
      patients. The outcome measures are socio-demographic and primary care workload
      parameters versus CTVBs by logistic regression analyses in a sample of 378
      patients (90% participation rate). People who pay little or no council tax are
      significantly less likely to live in owner-occupied homes or to have access to a
      car than their counterparts. There is also a significant inverse association
      between CTVB and demand for general practitioner services. CTVB could be an
      accessible, universal, non-census marker of UK socioeconomic status and of
      general practice workload that would have validity in the context of primary care
      resource allocation and is a concept worthy of further investigation.

PMID- 10962588
TI  - The methodology and operation of a pilot randomized control trial of the
      effectiveness of the Bug Busting method against a single application insecticide
      product for head louse treatment.
AB  - A Department of Health leaflet suggests two treatment methods for head lice:
      mechanical removal by wet combing; and insecticide lotion/rinses. However, there
      are no reports in the literature comparing the effectiveness of these two
      treatment methods and well controlled clinical trials of insecticide treatments
      are sparse. A pilot randomized control trial of the effectiveness of a specific
      method of wet combing, 'Bug Busting', against a single application of a
      proprietary insecticide product is reported. The difficulties of designing a
      trial are discussed and modifications that would allow a definitive trial to take
      place are suggested. The pilot study included enzyme analysis of lice for
      insecticide resistance status assessment.

PMID- 10962589
TI  - Incidence and socioeconomic determinants of abortion in rural Upper Egypt.
AB  - Because of a growing cultural and religious sensitivity and controversy over
      reproductive health issues, particularly abortion, this area remains relatively
      unexplored in Egypt. This study was conducted using a participatory approach to
      determine the morbidity and determinants of abortion in rural Upper Egypt. In
      all, 1025 women from six villages in Upper Egypt were included in the study.
      Information regarding the incidence of abortion, patterns of health care
      utilization and risk factors was obtained using a structured interview format.
      The local dialect was used in formulating questions and they were revised and
      amended by a panel of local leaders, interviewers and representatives of the
      study population. Interviewers were local educated (secondary or university
      level) female volunteers. Information about exposure to 17 risk factors was also
      collected and statistical analysis was done by estimating the odds ratio and
      applying a test of statistical significance. Then, a multivariate logistic
      regression model was applied to control for possible interactions and confounding
      effects. The results were that 40.6% (n=416) had aborted at least once; of them
      24.6% (n=252) had aborted more than once and were designated as recurrent
      aborters. The lifetime prevalence of recurrent abortion was estimated to be 25%
      and nearly 21% of pregnancies were aborted. The incidence of abortion was
      estimated to be 265 per 1000 live birth. Only 21.9% (n=91) of women received
      medical care for the last abortion. The vast majority of women (92%, n=299) who
      did not seek medical help received help from traditional and domestic sources.
      These sources are midwife (59.9%, n=179), relative or neighbour (29.8%, n=89),
      and traditional practitioner (10.4%, n=31). The multivariate analysis revealed
      that the incidence of abortion is significantly associated with gravidity,
      consanguinity, and mother occupation, while recurrent abortion is associated with
      gravidity, consanguinity and woman's age at marriage. In conclusion, the
      morbidity of abortion is a serious public health problem in Egypt. Because the
      incidence rate is very high and because safe abortion is limited in Egypt,
      maternal mortality due to abortion is expected to be underestimated. Promotion of
      family planning is expected to have a significant impact on the incidence of
      abortion in Upper Egypt.

PMID- 10962590
TI  - Assessment of health of senior executives in a developing country.
AB  - In a study of 202 senior executives, aged 25-64 y, in Benin City, Nigeria, the
      prevalence rate of hypertension was found to be 34.7%. Blood pressures increased
      with age for both sexes; however, the men had higher mean systolic and diastolic
      blood pressure and body mass indices (BMI) than the females. Contributing to this
      was a high level of inactivity, and diets high in carbohydrate and fat. High-risk
      social behaviour such as smoking and alcohol consumption was observed. It is
      recommended that management of the companies concerned put programs into place to
      assist this group of their workers to maintain a good health status, which will,
      in turn, improve their productivity.

PMID- 10962591
TI  - Health care for diabetic patients in developing countries: a case from Egypt.
AB  - The aim of this was to evaluate the pattern of care for diabetic patients in
      Alexandria as a model from a developing country. It is a cross-sectional multi
      centric. One thousand diabetic patients who had diabetes for no less than one
      year were randomly selected from 14 out-patient clinics and diabetic centres.
      Results showed that monitoring of the glycaemic state was based, almost entirely
      upon fasting blood glucose levels, with only a small minority (4%) having HbA
      measurements. During the previous 12 months, an electrocardiogram had not been
      performed in 26% of the subjects studies and the fundus was not examined in 38%.
      Twenty nine percent did not receive neurological examination, and feet were not
      inspected in 24%. Testing for albuminuria, serum creatinine, blood cholesterol,
      and triglycerides was performed only in 34%, 37%, 36% and 32% respectively.
      Patient's habits in seeking care revealed that 78% regularly attended the medical
      centre for follow up, 64% followed dietetic instructions, and 89% were compliant
      with prescribed therapy. Only 8% did self examination of blood glucose and 26%
      checked glucose in urine by themselves. Generally, the pattern of care provided
      for health insured diabetic patients is better than that received by non-health
      insured cases. It is concluded that in Egypt the quality of diabetes care differs
      in many aspects from the recommended standards and that structural as well as
      organisational improvements are urgently needed, particularly to guarantee
      adequate care to non-health insured patients.

PMID- 10962592
TI  - Antimalarials dispensing pattern by patent medicine dealers in rural settlements
      in Nigeria.
AB  - The pattern of antimalarial dispensing by Patent Medicine Dealers (PMD) was
      studied in 17 villages of Gokana (Ogoni Land) in Rivers State of Nigeria. Of the
      40 PMDs studied only eight (20%) had had formal health training and only eight
      could understand doctor's prescriptions. In total, 19 different types of
      antimalarials could be obtained from the individual ranges of antimalarials
      displayed by the 40 PMDs in the study. Chloroquine phosphate was the most
      frequently available. Twenty-three (57.5%) of PMDs administered Chloroquine at
      below the recommended dose of this drug. Twelve (30%) PMDs, eight with formal
      training and four others, administered the correct dose whilst five (12.5%) gave
      too much. All 40 of the PMDs studied knew how to dispense Daraprim and Fansidar
      correctly. We conclude that malaria control through prevention and treatment
      would be more effective if PMDs were to receive training on antimalarial
      dispensing alongside Community Health Workers.

PMID- 10962593
TI  - Poliomyelitis eradication programme: acute flaccid paralysis surveillance in
      mardin and five other provinces around Mardin, Turkey 1998.
AB  - After the successful eradication of small pox, the eradication of poliomyelitis
      was planned. In the poliomyelitis eradication programme, conducted since 1989,
      routine vaccination, supplemental immunisation activities and acute flaccid
      paralysis (AFP) surveillance were the main strategies. In 1997, in Mardin
      provinces six poliomyelitis cases were reported. Therefore it was planned to
      strengthen the eradication programme in this province and those around it. In
      1998 in Mardin and five neighboring provinces, a study was conducted that
      included monthly visits, educational activities, etc. At the result of this
      study, 64 AFP cases (22 of them poliomyelitis) were reported. Non-poliomyelitis
      AFP rate had increased from 0.9 in 1997 to 2.8 in 1998. An adequate two specimen
      ratio was 72%. We recognised that more poliomyelitis cases were reported in hot
      seasons when compared with non-poliomyelitis cases reported throughout the year.
      This difference was statistically significant (P<0.001). Most AFP cases were aged
      under 35 months. At the 60th day follow-up visits of the patients, we found 90.9%
      of the poliomyelitis cases but only 19.0% of the non-poliomyelitis case had
      residual paralysis. Presence of prodromal fever was another finding that
      distinguished poliomyelitis cases from non-poliomyelitis AFP cases. 90.9% of the
      poliomyelitis cases but only 64.3% of the non-poliomyelitis cases had fever at
      onset. This finding was also statistically significant (P<0.05).

PMID- 10962594
TI  - Correlated risk factors for suicidal ideation in aboriginal Southern Taiwanese
      women of childbearing age.
AB  - Suicide and non-accidental poisoning are two important causes of death of female
      aborigines in Taiwan. The purpose of this study was to estimate the prevalence of
      suicidal ideation and then to identify factors relating to this for female
      aborigines of childbearing age. Using stratified random sampling 212 female
      aborigines, aged between 20 and 49, were recruited into this study. Participants
      were interviewed at their homes by trained interviewers who used a structured
      questionnaire. The Suicidal Ideation Screening Questionnaire (SIS-Q) was used to
      help predict which participants would be more likely to have suicidal ideation.
      The prevalence rate of suicidal ideation within the previous 12 months was 20.3%
      (95% CI 14.9-25.7%). Significant related factors of suicidal ideation, which were
      analyzed by multiple logistic regression, revealed that women suffering
      depressive mood, living within a extended family, and perceiving poor health
      status were more likely to have suicidal ideation. Results generated from this
      study may be used, in primary care, for guidance as to how to prevent suicide.
      Outreach community programs incorporating a valid and sensitive screening
      instrument, such as the SIS-Q, should be implemented to help prevent suicides in
      aboriginal communities.

PMID- 10962595
TI  - Prevalence of cardiovascular risk factors of the smokers and non-smokers in the
      city of Debrecen, Hungary.
AB  - The aim of our study was to compare the major cardiovascular disease (CVD) risk
      factors of smokers and non-smokers. Risk screening of CVD was estimated by a
      questionnaire, via interview. Random samples of 20 000 inhabitants of Debrecen,
      Hungary, aged 30-65 y, took part in the study. 19 922 questionnaires were
      considered appropriate for further evaluation. 32.2% of the participants (n=6410)
      were smokers, whose data were compared to those of the 68.8% of non-smokers (n=13
      512). There were more male smokers than female (39.3% vs 27.7%), (P<0.001). 36.5%
      of males and 58.9% of females had not previously smoked regularly (P<0.001).
      24.2% of males and only 13.3% of females were able to stop smoking (P<0.001).
      8.7% of the participants smoked more than 20 cigarettes per day (14.8% of males,
      5.0% of females), (P<0.001). Smokers were younger, with a mean age of 43.4 y vs
      47.1 y for non-smokers (P<0.01). The ex-smokers and non-smokers had a higher body
      mass index than light, moderate and heavy smokers (26. 75+/-4.1 kg/m2 and 26.09+/
      4.3 kg/m2 vs 24.87+/-3.9 kg/m2 and 24. 89+/-4.2 kg/m2 and 25.32+/-4.3 kg/m2,
      respectively), (P<0.001). The results of the last measured blood pressures did
      not differ between the two groups. 94.8% of smokers and 93.6% of non-smokers did
      not perform any regular leisure time exercises (P<0.01). 39.8% of smokers
      regularly ate fatty food, in comparison to 28.0% of non-smokers (P<0.001). 30.6%
      of smokers vs 28.6% of non-smokers were factory workers while 69.4% of smokers vs
      71.4% of non-smokers did sedentary jobs (P<0.001). 2.3% of smokers vs 0.9% of non
      smokers admitted regular consumption of alcohol (P<0.001). Amongst the parents
      and brothers/sisters of smokers the prevalence of heart attack was higher 19.7%
      vs 18.7%, than for those of non-smokers (P<0. 05). We observed an accumulation of
      cardiovascular risk factors in the case of smokers, which indicates the higher
      susceptibility of smokers to CVD.

PMID- 10962596
TI  - Residues of tetracycline compounds in poultry products in the eastern province of
      Saudi Arabia.
AB  - Chicken muscle, liver and egg samples were collected from 33 broiler and 5 layer
      farms in the eastern province of Saudi Arabia over a period of two years starting
      from January 1996. Antibiotic-residue positive samples were identified in the
      products of 23 (69.7%) broiler and 3 (60%) layer poultry farms. 87% and 100.0% of
      the antibiotic-residue positive broiler farms were positive for at least one
      tetracycline compound in raw muscle and liver respectively, while 73.9% and 95.5%
      were positive for 2 or more tetracyclines in these two tissues, respectively.
      Furthermore, 82.6% and 95.5% of the antibiotic-residue-positive farms had mean
      concentrations of at least one tetracycline compound in excess of the permissible
      maximum residue limit (MRL) in raw muscle and liver, respectively. These
      compounds also remained chemically detectable after cooking. Tetracycline levels
      exceeded MRL in 14.4% of antibiotic-positive raw eggs but the overall mean
      tetracycline concentration in each farm was below MRL. This study confirmed
      widespread misuse of tetracycline agents including multiple use of drugs
      belonging to the same pharmacological group and lack of implementation of
      recommended withdrawal times. This may be contributing to the high resistance
      rates to tetracyclines in both chicken and human microbial isolates observed in
      the region. This study, therefore, stresses the need for stricter regulations for
      the use of antimicrobial drugs in the poultry industry as well as the inspection
      of chicken for drug residues prior to marketing.

PMID- 10962597
TI  - Spastic movement disorder.
AB  - This review deals with the neuronal mechanisms underlying spastic movement
      disorder, assessed by electrophysiological means with the aim of first, a better
      understanding of the underlying pathophysiology and second, the selection of an
      adequate treatment. For the patient usually one of the first symptoms of a lesion
      within the central motor system represents the movement disorder, which is most
      characteristic during locomotion in patients with spasticity. The clinical
      examination reveals exaggerated tendon tap reflexes and increased muscle tone
      typical of the spastic movement disorder. However, today we know that there
      exists only a weak relationship between the physical signs obtained during the
      clinical examination in a passive motor condition and the impaired neuronal
      mechanisms being in operation during an active movement. By the recording and
      analysis of electrophysiological and biomechanical parameters during a functional
      movement such as locomotion, the significance of, for example, impaired reflex
      behaviour or pathophysiology of muscle tone and its contribution to the movement
      disorder can reliably be assessed. Consequently, an adequate treatment should not
      be restricted to the cosmetic therapy and correction of an isolated clinical
      parameter but should be based on the pathophysiology and significance of the
      mechanisms underlying the disorder of functional movement which impairs the
      patient.

PMID- 10962598
TI  - Epidural electric stimulation of posterior structures of the human lumbar spinal
      cord: 1. muscle twitches - a functional method to define the site of stimulation.
AB  - OBJECTIVES: To describe an electrophysiological method for determining the
      relation between lumbar cord dorsal roots and cathode of epidural electrode for
      spinal cord stimulation (SCS). MATERIALS AND METHODS: Data has been collected
      from 13 subjects who have been under evaluation of effectiveness of SCS for
      control of spasticity. Induced muscle twitches from both quadriceps (Q),
      adductors (A), hamstrings (H), tibial anterior muscles (TA) and triceps surae
      muscles (TS) were simultaneously recorded with surface-electrode
      polyelectromyography (pEMG) and analyzed for amplitudes, latency times and
      recruitment order. RESULTS: Stimulation of dorsal lumbar cord structures evoked
      characteristic EMG events during muscle twitch responses. Their amplitudes varied
      with stimulus strength. Latency times were rather invariable regardless of
      stimulus strength. Two distinct recruitment orders were demonstrated depending on
      whether the stimulating cathode was placed over the upper (=response from
      quadriceps and/or adductor muscles) or the lower (=response from tibialis
      anterior and triceps surae) lumbar cord segments. The chances to stimulate upper
      lumbar cord segments are best around the 12th thoracic vertebra. CONCLUSIONS:
      pEMG recording of muscle twitches enables us to accurately differentiate between
      upper and lower lumbar cord segments. Furthermore, our findings regarding
      amplitude, latency and recruitment order strongly suggest that we stimulate
      posterior roots not posterior columns of the lumbar spinal cord.

PMID- 10962599
TI  - Comparison of spinal cord evoked potentials and peripheral nerve evoked
      potentials by electric stimulation of the spinal cord under acute spinal cord
      compression in cats.
AB  - STUDY DESIGN: Spinal cord evoked potentials and peripheral nerve evoked
      potentials after spinal cord stimulation were recorded under acute spinal cord
      compression in 19 cats. OBJECTIVES: To investigate the effects of acute
      compression upon grey matter and white matter by comparing both potentials.
      METHODS: We compared peripheral nerve evoked potentials, recorded at the biceps
      brachii branch of the musculocutaneous nerve, with descending spinal cord evoked
      potentials, recorded from the lumbar spinal cord, by stimulation to the C2 level,
      under compression of the C6 segment. RESULTS: The amplitude of both potentials
      decreased with increased compression. The second wave of peripheral nerve evoked
      potentials, which are motor fibre action potentials, decreased sooner than those
      of the spinal cord evoked potentials. CONCLUSION: These findings indicate that
      peripheral nerve evoked potentials are sensitive to acute damage of the segmented
      compression. This suggests that grey matter is more vulnerable to compression
      than white matter.

PMID- 10962600
TI  - The value of the Kurtzke Functional Systems Scales in predicting incomplete
      bladder emptying.
AB  - STUDY DESIGN: A field study was conducted in 40 patients with multiple sclerosis
      (MS) by comparing their residual urine volumes with the Kurtzke Functional
      Systems Scales for pyramidal (PFS) or bladder functions (BFS). OBJECTIVES: To
      determine whether raised residual urine volumes necessitating intermittent self
      catheterisation can be predicted by the PFS or BFS. SETTING: Department of Uro
      Neurology, The National Hospital for Neurology and Neurosurgery, University
      College London Hospitals Trust, London, UK. METHODS: In 40 patients with MS, post
      micturition residual volumes were measured with ultrasound prior to any treatment
      of bladder dysfunction. The patients' symptoms were assessed using PFS and BFS.
      Correlation between PFS, BFS and post micturition residual volumes were
      calculated as were sensitivity and specificity of PFS and BFS in predicting
      incomplete bladder emptying with residuals above 100 ml. RESULTS: None of the
      patients with a PFS or BFS of 0 or 1 had a residual of more than 100 ml. There
      was a linear progression of maximal residuals with PFS and BFS. Correlation
      between PFS (BFS) and the post micturition residual volumes was 0.37 (0.71).
      CONCLUSION: Unless a patient with MS has a PFS or BFS of greater than 1 they are
      unlikely to have incomplete bladder emptying with post micturition residual
      volumes above 100 ml. With PFS of BFS greater than 1 measurement of the post
      voiding residual volume is mandatory.

PMID- 10962601
TI  - Characteristic dynamic differences between healthy and low back pain subjects.
AB  - STUDY DESIGN: Open retrospective study. OBJECTIVES: To assess the functional
      capacity impairment of chronic low back pain (LBP) patients using characteristic
      dynamic changes. SETTING: Orthopaedics and Physiotherapy departments at Tel-Aviv,
      Israel. METHODS: Thirty-eight normal healthy volunteers and 607 chronic LBP
      patients were tested on a computerized 3-D lumbar dynamometer. The four major
      parameters measured were the maximal isometric torque (MIT), maximal velocity
      against 25% MIT and 50% MIT (MV25, MV50, respectively) and maximal torques in
      secondary axes (MST). All patients parameters were compared to the normal,
      healthy findings. RESULTS: All four parameters were found to be significantly
      different between healthy (or non-symptomatic) and symptomatic LBP subjects.
      CONCLUSIONS: The findings support the use of 3-D dynamometry and the four
      parameters mentioned to objectively classify patients with functional disability.

PMID- 10962602
TI  - An epidemiological description of spinal cord injuries in The Netherlands in
      1994.
AB  - STUDY DESIGN: Retrospective descriptive study. OBJECTIVES: To ascertain the
      incidence of spinal cord injury in The Netherlands. METHODS: From all patients,
      discharged from a Dutch general hospital in 1994 with the ICD-9 diagnosis code
      806 (fracture of the spine with injury of the spinal cord) and 952 (injury to the
      spinal cord without apparent spinal fracture), a copy of the anonymized medical
      correspondence was requested. The received correspondence was analyzed for the
      diagnosis of traumatic spinal cord injury with motor, sensory, bladder and bowel
      symptoms lasting longer than 2 weeks. RESULTS: 479 cases with the ICD-9 codes 806
      or 952 were identified. On 329 cases we received information. According to our
      criteria 126 cases had a spinal cord injury with persisting symptoms. Of these
      126 cases 18 died during hospital stay. Sex (77% male), level (57% tetra),
      completeness (48.7% complete), age distribution, cause of injury and incidence of
      stabilizing operation (44.2%) were assessed. Mean hospital stay was 31 days and
      of the subjects who survived the initial hospital phase, 70% were referred to a
      rehabilitation centre or a rehabilitation ward. CONCLUSION: The incidence of
      spinal cord injury surviving the acute phase in The Netherlands in 1994 was
      10.4/million/annum.

PMID- 10962603
TI  - Sitting position - posture and performance in C5 - C6 tetraplegia.
AB  - OBJECTIVES: To investigate how sitting position and seating affect posture and
      performance (balance, transfers, wheelchair skills, physical strain during
      wheelchair propulsion, spasticity and respiration) in persons with C5 and C6
      tetraplegia. SETTING: Outpatient clinic 'Spinalhalsan', Goteborg, Sweden. METHOD:
      Baseline measurements of sitting position and performance were performed followed
      by an intervention period. The intervention was individually adapted to each
      person with emphasis on reduction of kyphotic posture and pelvic obliquity.
      Furthermore, a functional requirement was that the new sitting position was used
      in everyday life and did not impair balance, transfers, wheelchair skills,
      physical strain during wheelchair propulsion, spasticity and respiration.
      RESULTS: Four persons with complete C5 - C6 tetraplegia who reported
      dissatisfaction with posture and seating took part in the study. A comparison of
      photographs before and after the intervention showed a reduction of kyphotic
      posture and pelvic obliquity. Balance, transfers, wheelchair skills, physical
      strain during wheelchair propulsion, spasticity and respiration were affected by
      the sitting position in an individual manner. CONCLUSION: Solution of problems
      concerning sitting and posture for persons with C5 - C6 tetraplegia requires good
      knowledge of the physical impairment, wheelchair adaptation, seating systems and
      cushions as well as an understanding of the individual's demands and wishes. Due
      to the complexity of the issue, standard solutions are not applicable. Thus, an
      analytical working method is required and co-operation between professionals -
      occupational therapists and physiotherapists - is important.

PMID- 10962604
TI  - Deltoid triceps transfer and functional independence of people with tetraplegia.
AB  - STUDY DESIGN: Matched case control study. SETTING: Two regional spinal units -
      Salisbury, UK (surgical centre) and London, UK (control centre). OBJECTIVE: To
      compare the functional independence and wheelchair mobility of spinal cord
      injured subjects, post deltoid triceps transfer, with matched control subjects.
      METHODS: Two matched groups of subjects, with tetraplegia resulting in triceps
      paralysis, were studied. The surgical group consisted of five of the six patients
      who had previously undergone deltoid triceps transfer at Salisbury. The control
      group (n=6) had not undergone surgical intervention but were comparable with
      respect to level of lesion, age, age at injury and duration of disability. All
      subjects completed standardised assessments of activities of daily living
      (Functional Independence Measure - FIM) and wheelchair mobility (10 m push and
      figure of 8 push). Surgical subjects completed additional questions, regarding
      the perceived effects of surgery on function. RESULTS: It was not possible to
      demonstrate absolute functional differences with the chosen outcome measures in
      this small series of matched case controls. All surgical subjects cited specific
      functional improvements since surgery and recommended the procedure. However the
      FIM lacked sufficient sensitivity to detect these changes. CONCLUSION: Further
      investigation of the functional outcome of deltoid triceps transfer in
      tetraplegia is warranted. Development of more sensitive outcome measures would be
      useful.

PMID- 10962605
TI  - The barrier effect of laminae: laminotomy versus laminectomy.
AB  - STUDY DESIGN: An experimental study to investigate whether replacement of the
      laminae (laminotomy) after subliminal procedures can prevent the invasion of scar
      tissue towards the dura. SETTING: Izmir, Turkey. METHODS: Laminectomy and
      laminotomy were performed at different levels on seven rats. Their spinal columns
      were investigated histopathologically after a period of 3 months. RESULTS: The
      histopathological evaluation revealed that the dura and spinal cord were involved
      by scar tissue at laminectomy area. However, this invasion was not observed at
      laminotomy levels. This study showed the barrier effect of laminae against
      fibroblastic activity. CONCLUSION: The barrier effect of lamina may affect the
      surgical outcome related to epidural fibrosis.

PMID- 10962606
TI  - Forced oscillation technique to detect and monitor tracheal stenosis in a
      tetraplegic patient.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To demonstrate forced oscillation
      technique's (FOT) utility in a tetraplegic patient with tracheostenosis. SETTING:
      A Rehabilitation Hospital, Brasilia, Brazil. METHODS: Serial evaluations of
      spirometry, bronchoscopy and forced oscillation assessment. RESULTS: A 16-year
      old male with C7 spinal cord injury, initially required mechanical ventilation
      and subsequent tracheostomy over a period of 4 weeks. Five months after the
      accident the onset of tracheostenosis was diagnosed. Flow-volume data were
      compatible with a fixed tracheal stenosis. FOT showed an obstructed pattern,
      manifested by high levels of resonance frequency and impedance. The FOT pattern
      returned to normal after dilatation. The FOT abnormalities recurred with two
      subsequent broncoscopicaly confirmed episodes of tracheal restenosis without
      parallel changes in spirometric parameters. CONCLUSION: This case suggests a role
      for FOT in the non invasive detection and follow up of tracheal stenosis. FOT may
      be particularly useful in tetraplegic patients, in whom the restriction from
      muscle weakness may make interpretation of forced expiratory flow-volume data
      problematic.

PMID- 10962607
TI  - Progress in spinal cord research - a refined strategy for the International
      Spinal Research Trust.
AB  - Achieving regeneration in the central nervous system represents one of the
      greatest intellectual and practical challenges in neurobiology, and yet it is an
      absolute requirement if spinal cord injury patients are to have any hope of
      recovery. The mission of the International Spinal Research Trust (ISRT),
      established in 1980, is to raise money specifically for spinal research, with a
      view to ending the permanence of paralysis caused by spinal cord injury. This
      review summarises some of the major steps forward made in recent years in
      understanding the mechanisms involved in spinal cord injury and where these
      discoveries fit in with the ISRT's overall objectives. We review approaches aimed
      at (1) preventing immediate adverse reactions to injury such as neuronal death
      and scar formation; (2) minimising inhibitory properties of the CNS environment
      and maximising the growth potential of damaged neurons; (3) understanding axonal
      guidance systems that will be required for directed outgrowth and functional
      reconnection; and (4) optimising the function of surviving systems. We also
      discuss 'infrastructural' prerequisites for applying knowledge gained through
      spinal research to the clinical condition, including basic scientific issues such
      as developing representative animal models of spinal cord injury and sensitive
      quantitative methods for assessing growth and functional restoration. In
      addition, we point out the importance of communication. The need to share
      knowledge between research groups is vital for advancing our understanding of
      injury and repair mechanisms. Equally important is the need for communication
      between basic scientists and clinicians which will be essential for what is the
      ultimate goal of the ISRT, the development of relevant treatment strategies that
      will prove beneficial to the spinal injured patient.

PMID- 10962608
TI  - Epidural electrical stimulation of posterior structures of the human lumbosacral
      cord: 2. quantitative analysis by computer modeling.
AB  - OBJECTIVES: Analysis of the computed recruitment order of an ensemble of ventral
      and dorsal root fibers should enlighten the relation between the position of a
      bipolar electrode and the observed order of muscle twitches. MATERIAL AND
      METHODS: Thresholds of selected spinal root fibers are investigated in a two step
      procedure. First the electric field generated by the electrodes is computed with
      the Finite Element Method. In the second step the calculated voltage profile
      along each target neuron is used as input data for a cable model. For every
      electrode position the electrical excitability is analyzed for 12 large diameter
      ventral and dorsal root fibers of the second and fourth lumbar and first sacral
      segment. The predictions of the neural responses of any target fiber are based on
      the activating function concept and on the more accurate computer simulations of
      the electrical behavior of all nodes and internodes in the vicinity of the
      electrode. RESULTS: For epidural dorsal lumbosacral spinal cord stimulation we
      found the following rules. (i) The recruitment order of the spinal roots is
      highly related to the cathode level. (ii) Dorsal root fibers have the lowest
      threshold values, ventral root fibers are more difficult to excite and dorsal
      columns are not excitable within the clinical range of 10 V. (iii) For a cathode
      close to the level of the spinal cord entry of a target fiber thresholds are
      lowest and spike initiation is expected at the border between cerebrospinal fluid
      and white matter; excitation of L4 roots is not possible with 210 micros/10 V
      pulses when cathode is more than 2.2 cm cranial to their entry level (1.5 cm for
      S1 roots; standard data). (iv) Cathodes positioned (essentially) below the entry
      level cause spike initiation close to the cathode, in a region where the fibers
      follow the descending course within the cerebospinal fluid. (v) At rather low
      stimulation voltage twitches are expected in all investigated lower limb muscles
      for cathodes below L5 spinal cord level. CONCLUSIONS: Our simulations demonstrate
      a strong relation between electrode position and the order of muscle twitches
      which is based on the segmental arrangement of innervation of lower limb muscles.
      The proposed strategy allows the identification of the position of the electrode
      relative to spinal cord segments.

PMID- 10962609
TI  - Long-term results of augmentation cystoplasty in spinal cord injury patients.
AB  - STUDY DESIGN: Prospective monocentric follow-up study. OBJECTIVES: To assess long
      term functional and urodynamic results of augmentation enterocystoplasty in
      spinal cord injury (SCI) patients with detrusor hyperreflexia and reflex
      incontinence who failed to respond to conservative treatment. SETTINGS:
      Department of Urology (Pitie-Salpetriere Hospital, Paris, France), Department of
      Neurological Rehabilitation (Raymond Poincare Hospital, Garches, France),
      Assistance Publique - Hopitaux de Paris, University Paris VI and V, France.
      METHODS: Prospective study of 17 SCI patients (four above T6 level, nine between
      T6 and T12, and four below T12) with history of refractory urge incontinence to
      pharmacotherapy. Partial cystectomy (subtrigonal for 15) was performed with
      Hautmann enterocystoplasty (15) or detubularized clam cystoplasty (two). RESULTS:
      Mean follow-up was 6.3+/-3.8 years (range 1.25 - 10.5 years). Fifteen of 17
      (88.5%) patients were completely continent under self clean intermittent
      catheterization (CIC) (mean 4.6/day, range 4 - 7). The remaining two patients
      with pudendal nerve denervation had persistent stress urinary incontinence. No
      operative complications were noted. Long-term complications included recurrent
      pyelonephritis for one patient. Maximal cystometric capacity increased from
      174.1+/-103.9 to 508.1+/-215.8 ml (P<0.05). Maximal end filling pressure
      decreased from 65.5+/-50.2 to 18.3+/-7.9 cm H2O (P<0.05). CONCLUSION: Urodynamic
      evaluation and clinical assessment demonstrate long-term success of augmentation
      enterocystoplasty in an homogeneous population (SCI) without delayed
      complications in SCI patients.

PMID- 10962610
TI  - Increased intracranial pressure in myelomeningocele (MMC) patients never shunted:
      results of a prospective preliminary study.
AB  - STUDY DESIGN: In some young adults non-shunted myelomeningocele (MMC) patients
      without symptoms or with unspecific clinical findings, moderate or severe
      stabilised ventriculomegaly are observed in control CT scans. Physicians are then
      faced with the so-called 'Arrested Hydrocephalus' (AH) syndrome. The present
      study is part of a prospective protocol in which patients with hydrocephalus
      associated with MMC and long-term clinical diagnosis of AH were included.
      OBJECTIVES: To evaluate myelomeningocele patients never shunted with clinical
      and/or CT scan criteria compatible with AH. SETTING: Multidisciplinary Spina
      Bifida Unit in a tertiary university hospital in Barcelona, Spain. METHODS:
      Fourteen MMC patients were selected, in all of them, continuous intracranial
      pressure (ICP) monitoring was performed. Analysis of the ICP records was done
      using the method described by Borgesen in mmHg. All patients were also studied by
      intelligence quotient (IQ) testing before and after shunting. RESULTS: The CT in
      all the study cases showed an Evans ratio </=0.30. The majority of patients
      (11/14) presented continuous high or intermittently raised ICP (active or
      unstable compensated hydrocephalus group) and in three (3/14) cases we confirmed
      the diagnosis of arrested hydrocephalus. There were no complications associated
      with ICP monitoring. CONCLUSIONS: In view of our results, we believe that in all
      non-shunted cases with clinical and/or CT scan criteria compatible with AH, the
      use of an objective method, such as continuous ICP monitoring, is necessary to
      diagnose arrested hydrocephalus, and a more comprehensive method that includes
      extensive neuropsychological valoration should be developed for the diagnosis and
      treatment of arrested hydrocephalus. SPONSORSHIP: Supported in part by Grant
      number 97-0923 from the Fondo de Investigaciones Sanitarias de la Seguridad
      Social (FISS).

PMID- 10962611
TI  - Reported quality of life of people with spinal cord injuries: a longitudinal
      analysis of the first 6 months post-discharge.
AB  - STUDY DESIGN: A repeated measures design was employed with measures taken on two
      observational periods during the first 6 months post-discharge from hospital.
      OBJECTIVES: To investigate the perceived importance of specific needs implicated
      in the development of quality of life (QOL), and the extent to which these
      aspects have been achieved, in a group of people with spinal cord injury (SCI)
      living in the community. SETTING: The National Spinal Injuries Centre, Stoke
      Mandeville Hospital and the general community. METHODS: The study sample
      comprised 24 spinal cord injured patients discharged from a national
      rehabilitation centre following a rehabilitation programme. The Quality of Life
      and Needs Assessment Questionnaire was completed by participants at 1 and 6
      months post discharge. RESULTS: No significant differences were found between the
      importance that participants attributed to specific needs at months 1 and 6 post
      discharge. Moreover, no significant differences were found between the extent to
      which these needs were met at 1 and 6 months post discharge. CONCLUSION: The
      reported quality of life of people who have a spinal cord injury remains stable
      during the first year following discharge.

PMID- 10962613
TI  - Never forget a faceellipsis?

PMID- 10962612
TI  - Cerebellar haemorrhage complicating resection of a cervical intramedullary
      tumour.

PMID- 10962614
TI  - Recognition of unfamiliar faces.
AB  - People are excellent at identifying faces familiar to them, even from very low
      quality images, but are bad at recognizing, or even matching, unfamiliar faces.
      In this review we shall consider some of the factors that affect our abilities to
      match unfamiliar faces. Major differences in orientation (e.g. inversion) or
      greyscale information (e.g. negation) affect face processing dramatically, and
      such effects suggest that representations derived from unfamiliar faces are based
      on relatively low-level image descriptions. Consistent with this, even relatively
      minor differences in lighting and viewpoint create problems for human face
      matching, leading to potentially important problems for the use of images from
      security videos. The relationships between different parts of the face (its
      'configuration') are as important to the impression created of an upright face as
      the local features themselves, suggesting further constraints on the
      representations derived from faces. We go on to consider the contribution of
      computer face-recognition systems to the understanding of the theory and the
      practical problems of face identification. Finally, we look to the future of
      research in this area that will incorporate motion and 3-D shape information.

PMID- 10962615
TI  - Self-recognition and the right prefrontal cortex.
AB  - Although the anatomical and functional substrates subserving face recognition
      have been subject to extensive investigation, the underpinnings of self-face
      recognition are not well understood. Given the evidence that own-face recognition
      has been demonstrated by a select number of species, it is intriguing to
      speculate whether self-face recognition is accomplished via a 'self-network' or
      simply a 'face-network' within the brain. Furthermore, the relationship of self
      recognition to other self-processes, such as self-evaluation and autobiographical
      retrieval, are not clearly defined. However, data from fMRI, ERPs and repetitive
      transcranial magnetic stimulation as well as from split-brain studies and
      patients with focal lesions, indicate that the prefrontal cortex, with possible
      right hemisphere lateralization, may be a preferential component in self
      recognition. Studies using these methods, as well as PET, have indicated that the
      self-processes of self-evaluation and autobiographical memory preferentially
      engage networks within the right fronto-temporal region. Although it is highly
      improbable that there is a 'self-recognition' or 'self' center, it appears that
      there may be a bias for the processing of 'self' within the right prefrontal
      cortex.

PMID- 10962616
TI  - What's new in visual masking?
AB  - A brief display that is clearly visible when shown alone can be rendered
      invisible by the subsequent presentation of a second visual stimulus. Several
      recently described backward masking effects are not predicted by current theories
      of visual masking, including masking by four small dots that surround (but do not
      touch) a target object and masking by a surrounding object that remains on
      display after the target object has been turned off. A crucial factor in both of
      these effects is attention: almost no masking occurs if attention can be rapidly
      focused on the target, whereas powerful masking ensues if attention directed at
      the target is delayed. A new theory of visual masking, inspired by developments
      in neuroscience, can account for these effects, as well as more traditional
      masking effects. In addition, the new theory sheds light on related research,
      such as the attentional blink, inattentional blindness and change blindness.

PMID- 10962617
TI  - Explaining derivational morphology as the convergence of codes.
AB  - Language users have a remarkable ability to create, produce and comprehend
      complex words. Words such as undercut and bakery appear to be composed of units,
      traditionally called morphemes, that recombine in rule-like ways to form other
      words, such as underline and cannery. However, morphological systems are
      quasiregular: they are systematic and productive but admit many seemingly
      irregular forms. Thus, bakery is related to bake and cannery to can but what is
      the groce in grocery? There is no bread in sweetbreads, liver in deliver, corn in
      corner or ginger in gingerly. Such words exhibit partial regularities concerning
      the correspondences between form and meaning, the treatment of which has
      important implications for linguistic and psycholinguistic theories. This article
      describes an approach to morphological phenomena called the convergence theory,
      in which morphology is a graded, inter-level representation that reflects
      correlations among orthography, phonology and semantics.

PMID- 10962618
TI  - Urethrocutaneous fistula due to a retained ring of condom.
AB  - Hidden foreign bodies have been described as a rare cause of both strangulation
      of the glans penis and urethrocutaneous fistula. We present the case of a 30-year
      old man who developed a urethrocutaneous fistula and penile shaft necrosis after
      a condom broke during intercourse. Neither the patient nor several physicians
      could identify the retained ring of condom, which had been buried under newly
      epithelialized skin. He underwent removal of the foreign body under general
      anesthesia, followed 5 months later by a formal urethrocutaneous fistula repair.

PMID- 10962619
TI  - [Nutritional disorders in chronic hepatic disease].

PMID- 10962620
TI  - [Normalization of menstrual cycles and pregnancy after liver transplantation].
AB  - The objective of the present study is to evaluate the effects of successful liver
      transplantation on menstrual cycles abnormalities and on reproductive function of
      women with chronic liver disease. Twelve women with age between 17 and 54 years
      who underwent liver transplantation were evaluated. The following variables were
      analyzed: age, etiology of chronic liver disease, pattern of menstrual function
      and period of amenorrhea before and after transplantation, and occurrence of
      pregnancy after transplantation. The mean age of patients was 36 +/- 12.6 years.
      Patients with primary biliary cirrhosis did not have menstrual abnormalities
      before transplantation. The other patients presented amenorrhea for 3 months to
      11 years before the transplantation. Rapid recovery of menstrual function was
      observed in all patients after the transplantation (3.1 +/- 1.2 months). Two
      patients became pregnant one and three years after the transplantation. It is
      concluded from this study that most women who present amenorrhea secondary to
      chronic liver disease have normal menstrual cycles in approximately three months
      following liver transplantation and they may become pregnant.

PMID- 10962621
TI  - [Varioliform gastritis: frequency and relationship with lymphocytic gastritis].
AB  - Varioliform gastritis is currently recognized as a special kind of chronic
      gastritis characterized by nodules, thickened fugal folds and erosions. These
      features appear to be unusual and different from those seen in chronic gastritis.
      The frequency of varioliform gastritis rarely exceeds 3% and the diagnosis can be
      easily made by endoscopic examination. Very little is known about the
      etiopathogeny, clinical significance and evolution of this disease. The role of
      Helicobacter pylori still remains unknown, although a close relationship between
      this gastritis and lymphocytic gastritis was suggested to exist over the last few
      years. The aim of the present study was to investigate the frequency of
      varioliform gastritis and its possible correlation with lymphocytic gastritis. To
      our knowledge, this is the first systematic study of varioliform gastritis in
      South America. We studied endoscopically 200 consecutive patients and found only
      one case of varioliform gastritis (0.5%). In a second part of the study, we
      examined histopathologically mucosa biopsies from 24 patients with varioliform
      gastritis and studied the presence of intraepithelial lymphocytes to verify the
      presence of lymphocytic gastritis. No case was found. We conclude that there was
      no correlation between varioliform gastritis and lymphocytic gastritis in our
      patients.

PMID- 10962622
TI  - [Intrahepatic transtumoral arteriovenous fistulae (diagnosis, importance,
      therapeutic proposals)].
AB  - The authors present the angiographic aspects of four patients having an
      arteriovenous transhepatic transtumoral fistula (two arterioportal and two
      arteriovenous). The angiographic results of the occlusion with cyanoacrylate
      (Hystoacryl) of the right hepatic artery in one and by the infusion of Lipiodol
      in two are also shown. The physiopathological characteristics of each kind of
      fistula are discussed and the consequences of the passage of the quimioembolizing
      mixture through the tumor, regarding intrahepatic abscess formation, irregular
      clinical results and pulmonary complications are commented. These complications
      make the diagnosis of a transtumoral transhepatic arteriovenous fistula,
      previously to the chemoembolic treatment important, even though being frequently
      difficult, because of the reduced caliber of the feeding artery and eventual low
      transfistular bloodflow. The efficient occlusion of the arterioportal fistula
      with Histoacryl was favourably compared to the infusion of Lipiodol, which was
      unable to occlude the arteriovenous fistula. The contraindication to perform
      chemoembolic treatment of hepatic tumors, when an intrahepatic transtumoral
      arteriovenous fistula is present and the embolization of the fistular feeding
      artery is stressed. Ultrasonography using color Doppler and sono-enhancing
      contrast is appointed as the ideal non-invasive means of making the diagnosis of
      an hepatic transtumoral fistula and makes it eligible to be the first test in the
      algorithm for the appraisal of hepatic tumors.

PMID- 10962623
TI  - Arrowroot as a treatment for diarrhoea in irritable bowel syndrome patients: a
      pilot study.
AB  - OBJECTIVES: Arrowroot is an old-fashioned remedy for diarrhoea, but no clinical
      studies have been done to evaluate its effectiveness. The aim of this pilot study
      was to assess its efficacy as a treatment for diarrhoea in 11 patients, all of
      whom had irritable bowel syndrome with diarrhoea as a feature. METHODS: The
      patients were interviewed and a questionnaire completed on entry into the trial.
      They then took 10 mL arrowroot powder three times a day for one month and
      discontinued the treatment for the subsequent month. Questionnaires were
      completed after one month on treatment and at the end of the trial after one
      month off treatment. RESULTS: Arrowroot reduced diarrhoea and had a long-term
      effect on constipation. It also eased abdominal pain. CONCLUSION: Arrowroot is an
      effective treatment for diarrhoea. Its action could be explained by several
      theories which relate to an increase in faecal bulk and thus a more efficient
      bowel action. The number of patients was small, and further studies are needed to
      substantiate preliminary results.

PMID- 10962624
TI  - [High temperature "mate" infusion drinking in a population at risk for squamous
      cell carcinoma of the esophagus].
AB  - "Mate", a popular hot infusion of a herb (Ilex paraguayensis) drunk in large
      volumes, is a known risk factor for squamous cell carcinoma of the esophagus and
      there is a suspicion that high temperature of boiled water used for the infusion
      may contribute for carcinogenesis. METHODS: We measured the temperature of "mate"
      infusion drunk by a sample of the population at risk for this carcinoma in
      Taquara, southern Brazil. We interviewed inhabitants for drinking habits and the
      temperature of the infusion was measured with high precision thermometers.
      Temperature of the infusion was asked to consumers and their estimate compared to
      our measurements. We considered 60 degrees C or higher as "hot". RESULTS: In 36
      residencies, 107 individuals were drinking "mate". Most individuals drank it
      daily (97.2%), and the medium daily volume was 1,265 ml (SD +/- 1,132 mL) ranging
      from 250 to 6,000 mL. The measured temperature was 60 degrees C or higher in 72%
      of residencies with medium of 63.4 degrees C (51-78 degrees C) and median 64.4
      degrees C. CONCLUSION: In this study, "mate" was consumed in large volumes at
      high temperature and individuals did not estimate correctly the temperature of
      infusion. High temperatures of "mate" may contribute to carcinogenesis in this
      population.

PMID- 10962626
TI  - [Hypocontraction of the esophagus in patients with Chagas' disease and with
      primary achalasia].
AB  - The esophageal contraction amplitude is low in patients with Chagas' disease and
      patients with primary achalasia but not every swallow is followed by low
      contraction amplitude. We evaluated the number of low contraction amplitude in 40
      normal volunteers, 99 Chagas' disease patients and 14 patients with primary
      achalasia. Each subject performed 10 swallows of a 5 mL bolus of water and the
      esophageal motility was measured at 5, 10 and 15 cm above the lower esophageal
      sphincter by the manometric method with continuous perfusion. The amplitude of
      contraction was considered to be low when its value was below 30 mm Hg. There was
      a hypotensive contraction when the amplitude was low or when the contraction
      failed. The number of hypotensive contractions was higher in patients with
      Chagas' disease and patients with achalasia than in healthy volunteers (P <
      0.05). Patients with Chagas' disease and abnormal esophageal radiological
      examination but without dilation had more frequent hypotensive contraction than
      patients with normal esophageal radiologic examination (P < 0.01). The same
      results were obtained for subjects with three or more hypotensive contractions (P
      < 0.01). The patients with Chagas' disease and dysphagia had more hypotensive
      contractions than patients without dysphagia (P < 0.05). We conclude that
      patients with Chagas' disease and patients with primary achalasia have a higher
      number of hypotensive contractions following wet swallows than normal volunteers,
      a fact that should influence the symptomatology of the patients.

PMID- 10962625
TI  - [Frequency of polyps in patients undergoing surgery for colorectal cancer].
AB  - INTRODUCTION: Epidemiologic and molecular biologic studies have already
      demonstrated that adenomatous colonic polyps are precancerous diseases. The main
      indication of the colonoscopy in the surveillance of colorectal cancer treated
      patients is the diagnosis and resection of adenomatous polyps. AIM: To study the
      frequency of adenomatous polyps after surgically resection of colorectal cancer.
      MATERIAL AND METHODS: Sixty eight patients, mean age 59 years old, with total
      resection of colorectal cancer, submitted to various colonoscopies during the
      follow up were studied retrospectively. The histological type and the
      characteristics of the polyp were described. RESULTS: The frequency of polyps was
      18%, being higher in the patients with more than 45 years (20%). The site of the
      polyps was in the left colon in 38% of the patients with cancer. The histological
      type of adenomas was tubular in 61%, villous in 22% and mixed in 17%. DISCUSSION:
      As described by other authors, the incidence of polyps were higher after 45 years
      old and more than a half of them were tubular. The frequency of polyps was higher
      in the first two years of follow up.

PMID- 10962627
TI  - Hepatitis C virus investigation in Pemphigus foliaceus (fogo selvagem) patients.

PMID- 10962628
TI  - [Isogenic islet transplantation on the rat liver (method for isolation and
      purification of the Langerhans islets)].
AB  - The major indication for pancreas or islet transplantation is diabetes mellitus
      type I. This process has to supply the insulin necessity keeping glucose under
      control. We have studied isogenic islet transplantation on the rat (WAG-RT1u)
      liver. The method of isolation and purification of the islets obtained 2.834 +/-
      551.64 islets with purity of 83 +/- 2.45%. Diabetes was induced by streptozotocin
      and seric glucose prior transplantation was 35 mmol/L. The islet transplantation
      of 2.834 +/- 551.64 islets in the rat liver has normalized glucose test from 9.62
      +/- 2.65 mmol/L 10 days after transplantation to 7.43 +/- 0.27 mmol/L later in
      the follow-up (P < 0.05). The median survival time of the islets was 73 days. In
      conclusion both the method of isolation and purification of the islets and islet
      transplantation was effective in the control of the diabetes induced by
      streptozotocin with median survival time of both islet and rat more than 73 days
      when rats were sacrified.

PMID- 10962629
TI  - [Nutritional consequences of metabolic impairment of macronutrients in chronic
      liver disease].
AB  - Liver chronic pathologies often courses with metabolic abnormalities of
      macronutrients leading to or aggravating a protein-energy malnutrition status.
      This review raised the major pathophysiological mechanisms related to the protein
      energy malnutrition in chronic liver patients. By large the reduced dietary
      intake is the most accepted cause particularly among alcoholic patients. Moreover
      during the treatment prevails the iatrogenic anorexia by unpalatable (restricted)
      diets interpolated with long-lasting fastings of hospitalized patients.
      Intestinal fat malabsorption is a common finding whereas hypermetabolism can be
      found associated with an acute alcoholism. Hypoglycemia or insulin resistance,
      hypertriglyceridemia and liver steatosis are common findings as well as lower
      plasma proteins along with higher levels of ammonia, aromatic and sulphur amino
      acids leading to neurological outcomes. The knowledge of these metabolic changes
      allow proper dietary interventions toward reduced morbi-mortality of those
      patients.

PMID- 10962630
TI  - [Hepatocellular carcinoma. Part 1. General considerations and diagnosis].
AB  - Several aspects are revised on the subject hepatocellular carcinoma related to
      its incidence/prevalence, risk and prognostic factors, cellular proliferation,
      pathological aspects, progression of chronic hepatitis B and C to cirrhosis and
      hepatocellular carcinoma, natural course of hepatocellular carcinoma, some
      clinical data, morphological diagnosis with special emphasis on radiological
      findings as ultrasound, dynamic computed tomography and magnetic resonance
      imaging, color-power Doppler, tissue and contrast harmonic.

PMID- 10962631
TI  - [Epidermoid splenic cyst a in child. Report of a case].
AB  - The authors present a case of epidermoid splenic cyst in masculine patient of 13
      years, that presented decrease of appetite, fever and alimentary vomits and
      tangible abdominal mass in the physical exam. Abdominal ultrasonography
      demonstrated expansible lesion in the topography of the spleen, and computerized
      tomography revealed intrinsic homogeneous lesion of the spleen, without
      communication with pancreas. To the laparotomy, cystic mass of great extension
      was observed, submitted total esplenectomy, being diagnosed in the
      histopatological exam epidermoid splenic cystic. In the follow-up patient
      developed with disappearance of the symptoms. The epidermoid splenic cyst are
      rare, they can be seen mainly in children and young adults, what proposes a
      congenital origin for this disease.

PMID- 10962632
TI  - [Isoniazid-induced hepatic failure. Report of a case].
AB  - Isoniazid and pyrazinamide are both well-known hepatotoxic drugs. When isoniazid
      is used, the hepatic lesion appears before than when pyrazinamide is used. This
      paper intends to relate a case of a 5-month-old patient who had lungs' and
      meningeal tuberculosis and who developed toxic hepatitis accomplished by hepatic
      failure while he was being treated with isoniazid, pyrazinamide and rifampicin.
      The clinic manifestations and the laboratory alterations were detected in the
      fifth day of treatment and the recovery was fast; and almost complete by the end
      of the first week, in which the use of isoniazid had been suspended. Although it
      was necessary to take the patient to the intensive care unit, he had a good
      recovery, without sequels.

PMID- 10962633
TI  - Causes of chronic pelvic pain.
AB  - Chronic pelvic pain (CPP) is a common and debilitating condition, and yet
      remarkably little is known about what causes the pain. In this chapter we present
      a model of CPP which emphasizes the multifactorial nature of the problem. A range
      of physical causes are discussed, including endometriosis, pelvic inflammatory
      disease (PID), adhesions, irritable bowel syndrome, interstitial cystitis,
      musculo-skeletal factors and nerve-related pain. The role of the nervous system
      in the genesis and moderation of pain is explored. The importance of
      psychological factors is discussed, both as a primary cause of pain and as a
      factor which affects the pain experience. As with other chronic syndromes, the
      biopsychosocial model offers a way of integrating physical causes of pain with
      psychological and social factors.

PMID- 10962634
TI  - Epidemiology of chronic pelvic pain.
AB  - An overview is given of the current knowledge of the epidemiology of chronic
      pelvic pain (CPP) in terms of prevalence, incidence, and associated risk factors.
      However, the lack of a consensus on the definition of CPP greatly hinders
      epidemiological studies. Although data are limited, the prevalence of CPP in the
      general population appears to be high. A single study found a 3-month prevalence
      (pelvic pain of at least 6 months' duration) of 15% in women aged 18-50 in the
      general US population. In the UK, an annual prevalence in primary care of 38/1000
      was found in women aged 15-73, a rate comparable to that of asthma (37/1000) and
      back pain (41/1000). The monthly incidence in primary care was 1.6/1000. No
      incidence figures exist for the general population. Analysis of risk factors for
      CPP is highly complicated owing to its multifactorial aetiology. At present, it
      is only of some value using women with CPP identified at community level, since
      those in primary, secondary or tertiary care are likely to constitute highly
      selected sub-groups.

PMID- 10962635
TI  - Psychosocial and economic impact of chronic pelvic pain.
AB  - According to a population-based estimate, chronic pelvic pain (CPP) affects
      approximately 15% of women aged 18-50. The psychosocial impact of CPP is
      reflected in mood disturbance, disruption of normal activity and relationships as
      well as pain. Identification of psychosocial factors as cause or effect remains
      problematic. Results of a study of 105 women with CPP using the British version
      of the SF-36 Health Survey Questionnaire are presented, together with analyses of
      face validity and reliability. While generally reflecting health status, specific
      problems with the questionnaire are identified related to the episodic nature of
      pelvic pain, and avoidance as a means of preventing pain exacerbations. Health
      economic analyses relating to CPP are reviewed and the implications for future
      directions in treatment strategy are discussed in the context of limited options
      of proven efficacy.

PMID- 10962636
TI  - Diagnostic value of radiological tests in chronic pelvic pain.
AB  - Chronic pelvic pain (CPP) presents a diagnostic as well as a therapeutic
      challenge to many clinicians. This chapter briefly describes the most frequent
      identifiable causes for CPP amenable to imaging; explains the most widely-used
      and widely available radiological tests for CPP; and compares/contrasts each
      test's utility and accuracy for a given causality. Examples of each imaging
      modality are included for demonstration purposes, and a summation table cross
      references the best diagnostic methods with corresponding disease processes.
      References from the literature of both radiology and gynaecology were used in
      preparing this review.

PMID- 10962637
TI  - The role of laparoscopy as a diagnostic tool in chronic pelvic pain.
AB  - More than 40% of laparoscopies are performed for the diagnosis of chronic pelvic
      pain (CPP). Although laparoscopic evaluation is sometimes considered a routine
      part of the evaluation, ideally the decision to perform a laparoscopy should be
      based on the patient's history, physical examination and findings of non-invasive
      tests. About 65% of women with CPP have at least one diagnosis detectable by
      laparoscopy and it is common to attribute causality to this diagnosis.
      Endometriosis is diagnosed in one-third of laparoscopies for CPP. Endometriosis
      requires histological confirmation to assure an accurate diagnosis. Adhesions are
      diagnosed in about one-quarter of laparoscopies. Ovarian cysts, hernias, pelvic
      congestion syndrome, ovarian remnant syndrome, ovarian retention syndrome, post
      operative peritoneal cysts and endosalpingiosis are other diagnoses that can be
      made laparoscopically in some cases. Laparoscopic conscious pain mapping has the
      potential to improve the accuracy of laparoscopy as a diagnostic tool in CPP.

PMID- 10962638
TI  - Medical management of chronic pelvic pain.
AB  - Chronic pelvic pain is a symptom of poorly understood aetiology. Pelvic
      congestion and psychological factors have been identified as important
      aetiological factors but surprisingly few studies of therapies directed at these
      aetiologies have been performed. A limited number of trials suggest that the
      progestagen medroxyprogesterone acetate may be useful in relieving symptoms, but
      benefit may be restricted to duration of treatment only. Further research is
      required into both the basis of chronic pelvic pain and its medical management.

PMID- 10962639
TI  - Surgical management of endometriosis.
AB  - A systematic literature review of the last two decades was performed to evaluate
      the effect of pelvic denervations in addition to conservative surgery on
      dysmenorrhoea and deep dyspareunia associated with endometriosis. Chronic pelvic
      pain relief after hysterectomy or adhesiolysis was also assessed. In the five non
      comparative studies on the effect of pre-sacral neurectomy, the frequency of
      dysmenorrhoea recurrence or persistence after treatment ranged from 4 to 40%. The
      pooled frequency of non-responders at the end of follow-up was 23% (95%
      confidence interval (CI), 19 to 27%). Only two of the three comparative, non
      randomized trials demonstrated a significant treatment benefit of pre-sacral
      neurectomy, and the results of the two identified randomized controlled trials
      are discordant. Significant quantitative heterogeneity among studies prevented
      pooling of data on dysmenorrhoea. The common odds ratio of deep dyspareunia
      persistence was 0.69 (95% CI, 0.31 to 1.54). In the 10 non-comparative studies on
      the effect of uterosacral ligament resection, the frequency of dysmenorrhoea and
      deep dyspareunia persistence after treatment ranged, respectively, from 0 to 50%
      and from 6 to 42%. The pooled frequency of non-responders at the end of follow-up
      was 23% (95% CI, 20 to 27%) and 13% (95% CI, 8 to 18%), respectively. Routine
      performance of complementary denervating procedures cannot be recommended based
      on the quality of the evidence available. The results of the five studies on the
      effect of hysterectomy on chronic pelvic pain of presumed uterine origin
      consistently demonstrated that 83-97% of operated women reported pain relief or
      improvement 1 year after surgery. There is no consensus on the outcome of
      adhesiolysis in patients with chronic pain, and the role of pelvic adhesions in
      causing symptoms is under scrutiny.

PMID- 10962641
TI  - Setting up a multidisciplinary clinic.
AB  - Chronic pelvic pain can be a perplexing and complex problem, frustrating to both
      clinicians and patients. The traditional medical and surgical model does not
      always relieve symptoms, and many patients suffer years of pain and undergo
      multiple surgical procedures without long-term benefit. The biopsychosocial model
      for chronic pelvic pain gives clinicians the opportunity to broaden the scope for
      management. A multidisciplinary team can offer simultaneous assessment and
      management of somatic, behavioural and psychosocial components of the pain. Key
      members of the team are identified and their roles explored. Practical aspects of
      operating a multidisciplinary clinic are discussed. A multidisciplinary approach
      comprises many elements. Further research is needed to identify which are the
      essential elements to secure optimum outcome for the individual patient.

PMID- 10962640
TI  - Pitfalls of the medical paradigm in chronic pelvic pain.
AB  - This article reviews specific clinical and philosophical problems in the medical
      and psychiatric literature on chronic pelvic pain since 1993. The problem of the
      dichotomy of 'organic' and 'psychogenic' pain has been well established in
      previous literature. The aim here is to consider recent developments purporting
      to respond to the impasse presented by this dichotomy. An evaluation of emergent
      trends towards multi-disciplinarity, and the 'biopsychosocial model' is
      developed. The resulting pitfalls discussed include the failure to develop
      understandings of the 'subjective' aspects of pain, the tendency to reduce causal
      processes to 'mechanisms', and the tendency to consider the psychosocial as
      purely reactive to the biological, inevitably positioned as prior. It is argued
      that these trends are only partial solutions to the problems and do not fully
      address the issues at stake. A greater diversity of theoretical and empirical
      perspectives needs to be introduced into medical research on chronic pelvic pain.

PMID- 10962642
TI  - Investigation of phenobarbital-carbamazepine-valproic acid interactions using
      population pharmacokinetic analysis for optimisation of antiepileptic drug
      therapy: an overview.
AB  - Antiepileptic drugs are associated with a wide range of drug interactions.
      Although monotherapy with antiepileptic drugs is preferred, patients with
      multiple seizure types or refractory disease generally require various
      combinations of antiepileptic drugs. Pharmacokinetic interactions between
      antiepileptic drugs represent a major complication of epilepsy treatment with
      polytherapy. It is important to be aware of possible interactions, so as to
      anticipate clinical effects and to reduce the risk of both toxicity and seizures
      worsening when a drug is added to, or withdrawn from, the patient's antiepileptic
      drug regimen. This report is an overview of the drug-drug interactions between
      antiepileptic drugs (phenobarbital<-->carbamazepine, carbamazepine<-->valproic
      acid and phenobarbital<-->valproic acid) by population pharmacokinetic analysis.

PMID- 10962644
TI  - Effect of black tea on lipid peroxidation in carbon tetrachloride treated male
      rats.
AB  - This study examined the effects of black tea (Camellia sinensis L.) on lipid
      peroxidation and glutathione levels in carbon tetrachloride (CCl4)-treated male
      Wistar rats. Three groups of rats formed two control groups and one treatment
      group. The control groups were fed with a standard diet, while the black tea
      group were fed the standard diet plus 6% by weight dried black tea leaves. After
      two months, the rats in the black tea group and in one control group were
      administered a single dose of CCl4 (1 ml/kg, i.p.) and sacrificed two hours
      later. Rats in the other control group were administered olive oil in a similar
      fashion. Lipid peroxide levels in liver and plasma, glutathione (GSH) levels in
      liver and alanine transaminase (ALT) and aspartate transaminase (AST) activities
      in plasma were measured. Rats in the black tea group were found to have
      significantly decreased liver lipid peroxide levels, and ALT and AST activities
      compared with the rats in the CCl4-treated control group. In addition, liver
      glutathione levels were decreased in the black tea group. These data suggest that
      black tea attenuates CCl4-induced hepatic injury.

PMID- 10962643
TI  - Interaction energy analyses of folate analog binding to human dihydrofolate
      reductase: contribution of the antifolate substructural regions to complex
      stability.
AB  - The three-dimensional structure of the human dihydrofolate reductase (DHFR),
      methotrexate tetrazole, and NADPH ternary complex was used to model the
      corresponding ternary complexes with methotrexate tetrazole replaced by
      methotrexate, methotrexate-polyglutamate with three glutamyl residues, and 5,10
      deazaaminopterin, respectively. Each complex was solvated in a 60-angstrom cube
      of explicit water and subjected to structural minimization followed by
      interaction energy analyses. Interaction energy calculations were performed for
      the antifolate interaction with water, NADPH, the DHFR binding site residues, the
      entire DHFR protein, and the solvated NADPH:DHFR complex. These studies revealed
      that methotrexate-polyglutamate exhibited the most stable interactions and that
      approximately one half of antifolate:DHFR stability could be accounted for by the
      interaction of the antifolate with the binding site residues. The antifolate
      structures were also subdivided into heterocyclic, phenyl, and glutamyl
      substructural regions. Interaction energies were subsequently calculated for the
      interactions of the subregions with water, NADPH, the DHFR binding site residues,
      the DHFR protein, and the solvated NADPH:DHFR complex. The glutamyl substructural
      region showed the greatest contribution to overall antifolate binding stability
      due to its interaction with the DHFR protein. The heterocyclic and phenyl
      substructural regions generally showed much less stable interactions. These
      results suggest that the primary stabilizing factor of the antifolate interaction
      is the interaction of glutamyl with the DHFR protein. Additionally, interaction
      energy analyses were performed for specific groups of atoms within the
      substructural regions. These studies indicated that the stability of the glutamyl
      interaction is due to the interaction of glutamyl oxygen atoms with the DHFR
      protein. In the case of the methotrexate tetrazole complex, the tetrazole
      nitrogens also contribute significantly to the stability of the glutamyl
      interaction. The carbon atoms of the heterocyclic and phenyl groups both showed
      more stable interactions with NADPH than with water, while the nitrogen atoms
      showed more stable interactions with water than with NADPH. Collectively, these
      results indicate that the glutamyl region is the most important in antifolate
      binding stability.

PMID- 10962645
TI  - The contributions of various chloroquine salts to the biliary and urinary
      execretion of hepatic paracetamol conjugation metabolites in the rat.
AB  - As an approach to explain the possible in vivo interaction of paracetamol
      (acetaminophen) with various chloroquine salts that are often administered during
      malaria tropica, the effects of these salts (chloroquine sulphate, chloroquine
      phosphate, chloroquine hydrochloride and ferrous sulphate) were examined in male
      rats. The coadministration of chloroquine salts with paracetamol for 7 days
      showed varied effects on urinary and biliary excretion of paracetamol sulphate
      and paracetamol glucuronide conjugates--the major metabolites of paracetamol
      metabolism. These findings suggest that chloroquine sulphate and ferrous sulphate
      may enhance the sulphation pathway in paracetamol metabolism and influence
      detoxification of paracetamol in the liver and thus protect the liver.
      Chloroquine sulphate is therefore a better choice compared to other chloroquine
      salts in the treatment of malaria with paracetamol as an antipyretic and
      analgesic.

PMID- 10962646
TI  - Can absolute oral bioavailability in humans be predicted from animals? A
      comparison of allometry and different indirect methods.
AB  - The objective of this study was to predict absolute bioavailability in humans
      from animal data using interspecies scaling as well as indirect approaches. Five
      different methods were used to predict absolute bioavailability in humans: (i)
      absolute bioavailability vs body weight (allometric approach); (ii) F =
      CL(IV)/CL(oral); (iii) F = 1-[CL(IV)/Q]; (iv) F = 1-[CL(oral)/Q]; and (v) F =
      Q/[Q + CL(oral)]. Methods II-V are indirect approaches, where predicted i.v. or
      oral clearance and hepatic blood flow (Q) (1500 ml/min) were used to predict
      absolute bioavailability in humans. Fifteen drugs were tested and the results of
      this study indicate that all five approaches predict absolute bioavailability
      with different degrees of accuracy, and are therefore unreliable for the accurate
      prediction of absolute bioavailability in humans from animal data. In conclusion,
      although the above-mentioned approaches do not accurately predict absolute
      bioavailability, a rough estimate of absolute bioavailability is possible using
      these approaches.

PMID- 10962647
TI  - The dangerous needles in the haystack of sore throats.

PMID- 10962648
TI  - Rheumatoid arthritis: a viral aetiology?

PMID- 10962649
TI  - Making job-sharing a success.

PMID- 10962650
TI  - Acute pancreatitis.
AB  - Acute pancreatitis is a common disease. As knowledge of its pathophysiology
      improves, evidence is found to confirm and refute present management and also to
      suggest new approaches. This article addresses some of these areas in the context
      of the management of acute pancreatitis.

PMID- 10962651
TI  - Chronic pancreatitis.
AB  - Chronic pancreatitis causes destruction of the pancreatic gland which leads to
      diabetes and malabsorption. Its principal cause is alcohol abuse, and intractable
      pain is the main clinical feature. The incidence of pancreatic carcinoma is
      increased among patients with chronic pancreatitis.

PMID- 10962652
TI  - Investigation of pancreatic disease.
AB  - The diagnosis of pancreatic disease is often difficult because of its
      retroperitoneal location and the non-specific nature of abdominal pain. There is
      no one test which provides all the information needed, and a series of
      complementary tests are generally required. This article discusses the different
      modalities available for investigating the patient with pancreatic disease.

PMID- 10962653
TI  - Magnetic resonance cholangiopancreatography.
AB  - Magnetic resonance imaging can now offer a robust and non-invasive diagnostic
      alternative to the established imaging investigations of the biliary and
      pancreatic ducts. This article briefly reviews the underlying principles,
      technique, pitfalls and clinical applications.

PMID- 10962654
TI  - Child psychiatry in Bombay: the school mental health clinic.
AB  - The school mental health clinic is an unusual amalgamation of the mental health
      and education sectors in Bombay. It aims to detect emotional problems in
      schoolchildren, increase mental health awareness in teachers and other
      professionals and determine any risk or causal factors in schoolchildren
      suffering from mental health problems. It also offers cross-cultural research
      opportunities.

PMID- 10962655
TI  - Topical tacalcitol treatment for psoriasis.
AB  - Multiple studies have shown the benefit of topical tacalcitol treatment for
      chronic plaque psoriasis. Tacalcitol ointment 4 micrograms/g is efficacious and
      well tolerated as both monotherapy and in combination with other treatments such
      as ultraviolet light therapy. It can be used all over the body including the face
      and scalp.

PMID- 10962656
TI  - Transportation of the critically ill and injured patient.
AB  - Transferring the seriously ill and injured is becoming a more formalized
      procedure in the UK. Whether from an accident site to medical care or between
      hospitals, the public expects that organized services are in place for safe
      patient transfer. As this is a developing subspeciality it is necessary to review
      the developments that have occurred over the previous 5 years.

PMID- 10962657
TI  - Peripheral infusion of Diazemuls.
AB  - Diazemuls is a very powerful anxiolytic agent with sedating and anti
      epileptogenic properties. Unfortunately, until now it has not been possible to
      give Diazemuls accurately and safely as an infusion. A new delivery system
      ensures that, as an infusion, this drug is potentially very effective in treating
      patients with terminal agitation, status epilepticus, drug and alcohol
      withdrawal.

PMID- 10962659
TI  - Sources of hospital cross-infection and other problems: observations of an
      inpatient.
AB  - This article gives the patient's viewpoint of a recent stay in hospital. The
      author highlights a number of issues and discusses the implications of her
      observations for hospital practice in the UK.

PMID- 10962658
TI  - Orthopaedic surgery in the elderly.
AB  - Demographic estimations for the UK predict an increase in the number of major
      orthopaedic surgical procedures in elderly people. The two major indications for
      surgery are osteoporotic fractures and severe osteoarthritis of weight-bearing
      joints. Coexisting medical disease makes elderly patients a surgical high-risk
      group, and mortality and morbidity after emergency surgery remains high.

PMID- 10962660
TI  - Modernizing the journal club.
AB  - Traditionally journal clubs provide a forum to learn presentation skills. We
      propose a new approach to teaching and learning in journal clubs, focusing on
      literature acquisition and critical appraisal skills. This approach will enable
      trainees to use journal clubs for personal professional development as well as
      for application of new knowledge in clinical medicine to improve patients'
      outcomes.

PMID- 10962661
TI  - Time to stop bullying and intimidation.
AB  - Bullying remains a familiar part of the health professional culture, despite the
      caring nature of doctors' work. Trainee doctors who feel threatened in the
      clinical workplace develop less effectively and are less likely to ask for advice
      or help when they need it. Most people who bully are not intrinsically bad
      people, but they must be helped to change, in the interests of patients as well
      as staff.

PMID- 10962662
TI  - Introducing critical appraisal.
AB  - All health-care professionals are being encouraged to use research evidence more
      in developing their clinical practice. To do this they need to inculcate the
      skills of 'critical appraisal'. Such skills involve assessing the appropriateness
      of research designs for answering clinical questions, critiquing the quality of
      the data gathering in individual studies, and assessing the implications of
      research findings.

PMID- 10962663
TI  - Mesenteric ischaemia and peptic ulcers.

PMID- 10962664
TI  - A simple sore throat?

PMID- 10962665
TI  - An unusual case of diphtheria and its complications.

PMID- 10962666
TI  - A woman with tetraparesis and missed beats.

PMID- 10962667
TI  - Self-regulation in the independent sector.

PMID- 10962668
TI  - Hypertension secondary to Marfan's syndrome.

PMID- 10962669
TI  - Preoptimization of the older elective patient.

PMID- 10962670
TI  - The future of radiotherapy and chemotherapy in head and neck cancer.

PMID- 10962672
TI  - History of the technological development of air conduction hearing aids.
AB  - This was a study of the history of the technological development of air
      conduction hearing aids, and a review of international literature on the subject.
      The technological evolution of amplification devices, from their origin to the
      present day, can be divided into seven distinct periods: the period of sound
      collectors, the period of hearing devices constructed from carbon, the period of
      vacuum tubes, the transistor period, the period of integrated circuits, the
      microprocessor period and the period of digital hearing instruments. Throughout
      these different stages, hearing instruments have progressively developed reaching
      their present state. The current era is itself undergoing constant development
      and change. With the introduction of new technologies, we expect that the rate of
      change will increase rapidly in the future.

PMID- 10962673
TI  - Stapedotomy in osteogenesis imperfecta patients.
AB  - Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by
      osseous fragility, blue sclerae and hearing loss. In order to assess the impact
      of stapedotomy on improving hearing on OI, a retrospective, one-group, pre-test
      post-test design was used to compare the pre-operative and post-operative
      audiograms of nine OI patients, treated with stapedotomy for their mixed hearing
      loss. Operative findings included fixation or thickening of the stapes footplate
      with normal superstructure configuration and hypervascularization of the
      promontory mucosa. Immediate post-operative results showed a significant
      improvement (p < 0.05) from 250-4000 Hz in air conduction and from 250-2000 Hz in
      bone conduction. A significant closure of the air-bone gap between 250-2000 Hz
      was also achieved (p < 0.05). The long-term results remained satisfactory with a
      mean threshold shift of 8 dB HL and an almost unchanged air-bone gap. These
      satisfactory results and the lack of complications make stapedotomy an appealing
      method for the management of OI-associated hearing loss.

PMID- 10962671
TI  - Cervical schwannoma: a case report and eight years review.
AB  - Schwannomas are peripheral nerve tumours of nerve sheath origin. We report one
      case of cervical schwannoma originating from the brachial plexus. A 56-year-old
      man presented with a slow-growing mass on the right side of his neck that had
      been noted for more than 10 years. During operation, a well-encapsulated mass was
      seen beneath the brachial plexus with adhesion to the plexus element. It was
      reported as a schwannoma. Three days after surgery, the patient had a motor
      deficit of the right upper arm and neurological examination showed a CV nerve
      deficit. The neurological function recovered completely after three months. In
      addition, the other five cases of cervical schwannoma seen in our hospital
      between March 1990 and June 1998 are also reviewed. All patients had surgery. The
      pre-operative symptoms, impressions, and post-operative neurological status were
      shown and discussed. Only two cases were diagnosed as neurogenic tumour pre
      operatively. Post-operatively, one patient had transient neurological deficit and
      another one had permanent deficit.

PMID- 10962674
TI  - Long-term middle-ear effects of middle-ear/eustachian tube packing after
      translabyrinthine surgery.
AB  - The purpose of this study was to evaluate the long-term effect on middle ear and
      eustachian tube function following the packing of the middle-ear space to prevent
      cerebrospinal fluid rhinorrhoea at the termination of translabyrinthine
      vestibular schwannoma removal. This was an observational study of a sample of 14
      patients examined between two and five years post-operatively. Photo-otoscopy and
      tympanometry were performed bilaterally to evaluate appearance and function. All
      operated middle ears were air-containing although eight out of 14 showed scarring
      as evidence of operative intervention. There were no drum retractions. Ten out of
      14 middle-ear compliance peaks were lower in the operated ear with four flat
      traces. Two out of 14 were the same and two out of 14 showed high compliance. The
      middle-ear pressure was always within the normal range when determinable. This
      technique appears to have no detrimental effects on the middle ear and does not
      permanently obliterate the eustachian tube. The reduced compliance in the
      majority of cases is probably a result of scarring and fibrosis. When drum
      hypermobility is seen this is accounted for by incus removal.

PMID- 10962675
TI  - Burow's solution in the treatment of active mucosal chronic suppurative otitis
      media: determining an effective dilution.
AB  - Burow's solution (13 per cent aluminium acetate) has been found to inhibit in
      vitro the growth of most commonly occurring bacteria found in the discharging
      ear. An in vitro study has shown that the minimum inhibitory concentration of
      Burow's solution for these organisms lies between a 1:80 and a 1:160 dilution.
      This paper reports on a clinical trial that incorporated 67 discharging ears to
      establish the most effective strength of aluminium acetate solution. There was no
      statistical difference in the effectiveness of full strength Burow's solution
      compared to 3.25 per cent aluminium acetate solution (a quarter strength Burow's
      solution). Response rates of 80.8 per cent and 75 per cent respectively following
      a two-week treatment period were achieved using these two solutions. A 1.3 per
      cent aluminium acetate solution (1/10 strength Burow's solution) was found to be
      markedly inferior. Bacteriological and audiological profiles were recorded for
      each patient.

PMID- 10962676
TI  - Contact endoscopy of the larynx: a quantitative study.
AB  - Contact endoscopy is a technique of obtaining detailed magnified images of living
      epithelium, using a modified glass rod lens endoscope placed on the surface of
      the tissue. The technique has been extensively described in gynaecological, and
      more recently, laryngeal and nasal tissues. However, no quantitative studies of
      its diagnostic accuracy yet exist. A prospective partially blinded controlled
      study of eight cases with a variety of laryngeal pathologies is described. A
      single pathologist with no knowledge of the ultimate histological diagnoses
      successfully identified six of eight laryngeal pathologies on contact endoscopic
      findings, while the other two cases were identified to a degree of accuracy that
      was sufficient to positively identify the need for standard tissue biopsy. The
      advantages and disadvantages of the technique are described, along with
      suggestions for its role in clinical practice.

PMID- 10962678
TI  - Medial displacement of grommets: an unwanted sequel of grommet insertion.
AB  - Grommet insertion is one of the commonest surgical procedures performed in the
      UK. We have come across three cases in which grommets have displaced medially in
      the middle ear after establishing a satisfactory post-insertion position. We
      suggest that an abnormally long myringotomy incision and improper placement of
      the grommet are responsible for this unwanted outcome.

PMID- 10962677
TI  - Presumed laryngo-pharyngeal reflux: investigate or treat?
AB  - A review of a combined gastroenterology and laryngology clinic was conducted to
      determine the effectiveness of treatment and the predictive value of clinical
      findings and investigations. Data were collected prospectively. Investigations
      were performed according to clinical criteria. Patients with symptoms suspected
      to be due to laryngopharyngeal reflux (based on a positive oesophageal pH test
      and/or changes on videolaryngoscopy consistent with posterior laryngitis) were
      treated with omeprazole for at least two to three months. There were 87 patients;
      the most common symptoms were cough (38 per cent) and hoarseness (36 per cent);
      77 per cent had some symptoms suggestive of gastro-oesophageal reflux. Sixty
      seven patients were given omeprazole. A good response to laryngo-pharyngeal
      symptoms was seen in 37 patients (55 per cent). The presence of reflux symptoms
      was not a predictor of a good response. Increasing severity of oesophageal acid
      exposure over the 24 hours of pH testing was associated with a better symptom
      response (Spearman rank correlation, p = 0.01). Posterior laryngitis was not
      associated with the response to treatment, although there was a trend towards an
      association between improvement in laryngitis (after treatment) and improvement
      in symptoms (p = 0.08). The response to proton pump inhibitors was lower than
      other published results. Oesophageal pH monitoring may have a role in predicting
      which patients will respond to proton pump inhibitors. This study does not
      support the decision to treat with anti-secretory therapy, based only on the
      presence of posterior laryngitis.

PMID- 10962679
TI  - Human auricolar myiasis caused by Wohlfartia magnifica (Schiner) (Diptera:
      Sarcophagidae): first case found in Sardinia.
AB  - The authors report a case of myiasis of the middle ear caused by Wohlfartia
      magnifica Schiner (Diptera: Sarcophagidae). The entomological aspects, the
      clinical epidemiological characteristics and the therapeutic solutions of this
      disease are evaluated. In particular, they underline the rarity of myiasis both
      because of the aetiologic agent and the anatomical site. The therapeutic aspects
      are also reported and discussed.

PMID- 10962681
TI  - New method for the effective instillation of nasal drops.
AB  - The main cause of sinus pathology is disease in the middle meatus, therefore,
      unless nasal drops are deposited in this site they will not be effective.
      Currently, one of three standard head positions are used by patients for the
      instillation of nasal drops, 'head back', 'praying to Mecca', and 'Mygind's', all
      are uncomfortable and only one, Mygind's position, effectively deposits the drops
      in the middle meatus. In this paper, we review these three positions by utilizing
      a preserved cadaver head and conducting a simple gravitational flow study using
      white liquid latex as a nasal drop substitute. We also describe a new fourth
      'Ragan' position, on the side, head down, that is effective in consistently
      delivering nasal drops into the middle meatus and should prove a most comfortable
      position for patients to adopt.

PMID- 10962680
TI  - Cavernous haemangioma of the internal auditory canal.
AB  - Cavernous haemangiomas are rare lesions of the cerebello-pontine angle that can
      mimic the more commonly occurring vestibular schwannoma. A case report involving
      a patient with a cavernous haemangioma of the internal auditory canal (IAC)
      highlights this as a diagnostic possibility for lesions of the IAC by comparing
      and contrasting the clinical and radiological findings with the more commonly
      occurring vestibular nerve and facial schwannomas. Symptoms such as hearing loss
      and facial paralysis that are disproportionate to the size of the lesion or
      fluctuate with hormonal changes such as those seen in pregnancy are suggestive of
      haemangioma. Radiological imaging demonstrating a lesion enhancing with
      gadolinium and containing areas of calcification is also suggestive of
      haemangioma. It is important to consider the possible diagnosis of haemangioma as
      early recognition of this entity may improve the chances of preserving the
      functional integrity of the facial nerve.

PMID- 10962682
TI  - Juvenile xanthogranuloma of the nasal cavity.
AB  - Juvenile xanthogranuloma is a benign, normolipaemic, self-healing condition and a
      type of histiocytosis that occurs most frequently in infants and children. This
      condition usually presents with solitary or multiple cutaneous lesions and
      occasionally with visceral lesions. We report a case of juvenile xanthogranuloma
      occurring in the nasal cavity. We believe this is the first report, in the
      English literature, of juvenile xanthogranuloma occurring in this site.

PMID- 10962683
TI  - Rhinorrhoea feigning cerebrospinal fluid leak: nine illustrative cases.
AB  - Before contemplating surgery for cerebrospinal fluid (CSF) rhinorrhoea it is
      vital that the correct diagnosis is established. This can be done using
      immunofixation of beta-2-transferrin, that is nearly always positive in cases of
      CSF rhinorrhoea. Fluorescein lumbar puncture is useful in establishing the exact
      site of a leak and also in confirming the absence of a leak where the clinical
      suspicion is high but the beta-2-transferrin is negative. High resolution
      computed tomography (CT) scanning is a useful radiological investigation for
      identifying a bony defect. We present nine patients who presented with clear
      rhinorrhoea that was clinically highly suggestive of a CSF leak. Three of these
      patients had undergone previous craniotomies for presumed CSF rhinorrhoea. The
      diagnosis of CSF rhinorrhoea was excluded in all patients using beta-2
      transferrin with or without fluorescein lumbar puncture. The authors believe that
      measurement of beta-2-transferrin should be mandatory before surgery for CSF
      rhinorrhoea.

PMID- 10962684
TI  - Lipoma in fossa of Rosenmuller.
AB  - We report the first case of a lipoma originating in the fossa of Rosenmuller.
      Although lipomas are a common benign tumour in the body, lipomas of the
      nasopharynx are rare.

PMID- 10962686
TI  - Oropharyngeal foreign body.
AB  - An unusual extremely benign course of an 8 cm long, rusting, metallic
      oropharyngeal foreign body that had entered post-aurally (penetration injury)
      four years previously to lie completely within the pharyngeal lumen has not yet
      been reported in the world literature. The need for additional investigations and
      special precautions to be taken during surgical extraction are highlighted.

PMID- 10962685
TI  - Oesophageal ulceration caused by doxycycline: an unusual complication.
AB  - Oesophageal ulceration is an unusual complication of doxycycline treatment
      (Vibramycin) presenting to an Otorhinolaryngology department. A case report is
      presented with discussion of investigations and management of the patient.

PMID- 10962687
TI  - Transcervical foreign body.
AB  - The uncommon occurrence of acute retropharyngeal abscess in adults can be the
      result of a retained foreign body. A large piece of wood impacted in the neck in
      a road traffic accident and presenting as retropharyngeal and bilateral
      parapharyngeal abscesses is reported for its rarity and clinical interest.

PMID- 10962688
TI  - Submandibular hydatid cyst caused by Echinococcus oligarthrus.
AB  - An unusual case of Echinococcus oligarthrus infestation of the submandibular
      salivary gland is reported. Echinococcus oligarthrus is a rare variant of the
      Echinococcus species affecting humans. To the best of our knowledge only one case
      of submandibular hydatid cyst caused by Echinococcus oligarthrus has been
      reported. A 28-year-old female patient was admitted with a progressively
      increasing swelling in the left submandibular region of four years' duration.
      There was no pulmonary or hepatic involvement. The present case of submandibular
      hydatid cyst caused by Echinococcus oligarthrus is of interest because of the
      unusual site of the disease.

PMID- 10962689
TI  - Adenoid cystic carcinoma of the tongue.
AB  - Malignant tumours of the salivary glands in children are extremely rare. We
      present here a 12-year-old girl initially diagnosed as pleomorphic adenoma on
      fine needle aspiration biopsy, and adenoid cystic carcinoma (ACC) after the
      lesion was excised and examined by histopathology. A wide resection of the lesion
      and bilateral supraomyohyoid neck dissection was performed. To our knowledge this
      is one of the youngest patients with ACC of the minor salivary glands. Due to its
      benign histological appearance, the biological agressiveness of ACC is usually
      underestimated. Although fine needle aspiration cytology (FNAC) is very valuable
      in diagnosis, cytological variations of pleomorphic adenoma must be considered.
      ACC of the tongue in a young age group should be treated with wide resection and
      selective neck dissection if the tumour is localized in places where the risk of
      metastasis is increased and if there is a clinically palpable lymph node. In such
      cases the clinician should not avoid radical operations even in a young patient.

PMID- 10962690
TI  - Intraductal papilloma of the submandibular gland.
AB  - Salivary tissue intraductal papillomas are rare, benign tumours that
      predominantly affect minor salivary glands. We report a case of an intraductal
      papilloma arising in the unusual site of the submandibular gland. The tumour was
      completely excised and recurrence is not expected. A brief review of this
      histologically distinct lesion is presented.

PMID- 10962691
TI  - Observer variability in optic disc assessment: implications for glaucoma shared
      care.
AB  - Demonstrating that optometrists can make valid and reliable assessments of optic
      disc features is an important prerequisite for establishing schemes for shared
      care/co-management. Previous studies have estimated observer variability among
      experts in the assessment of optic disc cupping, but there has been a paucity of
      information on observer variability amongst optometrists. This paper describes a
      study to investigate intra- and inter-observer variability for a range of disc
      features, as graded by both ophthalmologists and optometrists. Five observers
      (three optometrists and two ophthalmologists) graded 48 stereo-pairs of optic
      disc photographs from 48 patients on two separate occasions. Each observer graded
      the following features: vertical and horizontal C/D ratios, narrowest rim width,
      the presence/absence of a disc haemorrhage, focal pallor of the neuroretinal rim,
      peri-papillary atrophy, the steepness of the cup-edge and the presence/absence of
      the cribriform sign. The average intra- and inter-observer standard deviation
      (SD) of differences are, respectively, 0.11 and 0.19 for the vertical C/D ratios
      and 0.10 and 0.18 for the horizontal C/D ratios. For the vertical C/D ratio the
      average weighted kappa (kappa w) is 0.79 within observers and 0.46 between
      observers. Percentage agreements for the presence/absence of a disc haemorrhage
      range from 96 to 100% (average kappa = 0.92) within observers and from 90 to 98%
      (average kappa = 0.77) between observers. For other disc features, average kappa
      w values range from 0.67 to 0.71 within observers and from 0.23 to 0.46 between
      observers. Intra- and inter-observer comparisons (within and between different
      professionals) across all disc features are comparable for the optometrists and
      ophthalmologists, thus demonstrating that optometrists can make valid assessments
      of disc features. The implications for shared care are discussed.

PMID- 10962693
TI  - Optical Fourier filtering for whole lens assessment of progressive power lenses.
AB  - Four binary filter designs for use in an optical Fourier filtering set-up were
      evaluated when taking quantitative measurements and when qualitatively mapping
      the power variation of progressive power lenses (PPLs). The binary filters tested
      were concentric ring, linear grating, grid and "chevron" designs. The chevron
      filter was considered best for quantitative measurements since it permitted a
      vernier acuity task to be used for measuring the fringe spacing, significantly
      reducing errors, and it also gave information on the polarity of the lens power.
      The linear grating filter was considered best for qualitatively evaluating the
      power variation. Optical Fourier filtering and a Nidek automatic focimeter were
      then used to measure the powers in the distance and near portions of five PPLs of
      differing design. Mean measurement error was 0.04 D with a maximum value of 0.13
      D. Good qualitative agreement was found between the iso-cylinder plots provided
      by the manufacturer and the Fourier filter fringe patterns for the PPLs
      indicating that optical Fourier filtering provides the ability to map the power
      distribution across the entire lens aperture without the need for multiple point
      measurements. Arguments are presented that demonstrate that it should be possible
      to derive both iso-sphere and iso-cylinder plots from the binary filter patterns.

PMID- 10962692
TI  - Transverse chromatic aberration and colour-defined motion.
AB  - A number of recent studies have explored the role of the chromatic system in
      motion processes using the isoluminance paradigm. A major concern when using such
      methodological procedures is potential artefacts produced by chromatic
      aberrations. In the present study we address the problem of optically induced
      luminance artefacts produced by transverse chromatic aberrations (TCA), which may
      contaminate the results obtained in chromatic motion-nulling experiments. Results
      show that different TCA levels artificially increase chromatic motion sensitivity
      values to varying degrees above 0.5 cpd for red/green gratings. The data also
      suggest the notion that naturally occurring TCA can decrease motion-nulling
      thresholds for chromatic gratings at high spatial frequencies. Furthermore, our
      data show that the motion-nulling paradigm for chromatic gratings may in fact be
      an efficient functional method for assessing the amount of TCA produced by
      optical factors.

PMID- 10962694
TI  - The depth, contour and angle of the glazing grooves of spectacle frames: don't
      blame the glazer?
AB  - The groove of a spectacle frame is responsible for lens retention. It also tends
      to fill with unsightly dirt which cannot be readily removed by our patients. The
      results of this investigation would suggest that both loose spectacle lenses and
      dirt accumulation may often be due to poor quality control in the frame industry.
      The data also suggests that unwanted stress may be present in both frames and
      lenses due to non-optimal groove shape.

PMID- 10962695
TI  - Effects of prediction on timing and dynamics of vergence eye movements.
AB  - Periodic square waves were used to generate predictable vergence eye movement
      responses. The timing and dynamic characteristics of vergence eye movement
      responses to predictable and non-predictable stimuli were compared. Results
      showed significant changes in timing characteristics along with a highly
      characteristic anticipatory movement in the early part of predictable vergence
      responses. This phenomenon is similar to that seen in saccadic eye movements and
      appears to influence the timing and dynamics of the subsequent vergence response.
      A model-based analysis of dynamics showed that the pulse width, pulse gain, and
      step gain of the motor command signal did not show major differences between
      predictable and non-predictable response. However, other model parameters related
      to the acceleration of the response showed a substantial decrease when the
      movements were predictive.

PMID- 10962696
TI  - Spatial location studies on the chemical composition of human tear ferns.
AB  - Tear ferns are the patterns formed when tears are allowed to dry on a clean
      smooth surface. The patterns have been categorised according to confluence of
      pattern, with less confluent ferns indicative of tear film abnormalities. Little
      is known about the mechanism that gives rise to this phenomenon. Previous work
      has concentrated on correlation of alterations in tear film composition on the
      ferning phenomenon. The present study takes a new approach by analysing the
      locations of chemical elements in the fern to understand how the ferns form. By
      means of SEM coupled with EDXA, Na, K and Cl were detected within the fern.
      Sulphur, indicative of the presence of macromolecules such as mucins and
      proteins, was only found at the very periphery of the dry tear drop. The results
      suggest that macromolecules do not play a direct role in the formation of the
      ferns. A model is put forward to explain the observation whereby proteins and
      mucins are precipitated selectively by increasing salt concentration at the drop
      margin.

PMID- 10962697
TI  - Aging, perception, and visual short-term memory for luminance-defined form.
AB  - The sensory, perceptual, and visual short-term memory (VSTM) capacity of young
      and older observers for processing luminance-defined shape information was
      assessed in a series of experiments. The following were assessed: each
      individual's threshold necessary to detect a square from its background as
      measured by luminance thresholds; the capacity for making simultaneous size
      discriminations when compensating for individual differences in sensory input;
      the capacity for making sequential size discriminations; and the capacity for
      remembering size differences over time. The results show a selective deficit for
      simultaneous perceptual processing for older subjects, which cannot be attributed
      to differences in sensory input, task difficulty, interhemispheric transfer, or
      VSTM.

PMID- 10962699
TI  - Spectral filters in low-vision correction.
AB  - Coloured filters are used to protect the lens, retina and other ocular tissues
      against the hazard of light damage and to improve the quality of vision mainly in
      cases of ocular media opacities. Four types of yellow, amber and orange filters
      have been designed as tinted glasses, shields and colour covering of spectacles.
      They were tested on 15 adult patients with partial cataract and on 80 children
      with congenital pathology (i.e. macular hypoplasia, albinism, aphakia after
      congenital cataract). The majority of the children had nystagmus. The filters
      with particular spectral characteristics provide reduction of light intensity in
      the light-damaging range by at least a factor of five. Optimal filters were
      selected by examination of visual acuity, contrast frequency sensitivity, glare
      sensitivity and subjective selection by the patients. The effects of filters
      were: 11-43% increase in corrected visual acuity, 27-34% increase in contrast
      sensitivity function (CSF) for all frequencies and a marked reduction in glare
      sensitivity. All patients reported subjective improvement including reduction of
      photophobia, eye-strain and eye discomfort. It is concluded that coloured filters
      are able to contribute substantially to rehabilitation of low-vision patients.

PMID- 10962698
TI  - Age-related changes of defocus-specific contrast sensitivity in healthy subjects.
AB  - To investigate the effect of defocus on contrast sensitivity as a function of age
      in healthy subjects, the through focus contrast sensitivity was measured in 100
      healthy subjects aged 20-69. Defocus-specific changes in contrast sensitivity
      reflect age-related changes in the optics of the eye. Tests were performed in
      cycloplegic eyes varying artificial pupil size (2, 4 and 6 mm), defocus (-1 to +2
      D), and spatial frequency (1-16 cpd). Integrated contrast sensitivity was taken
      as a measure for the total amount of visual information transferred by the
      optical media. At optimal focus, integrated contrast sensitivity and log contrast
      sensitivity at 8 cpd showed a significant age-related decline. The log contrast
      sensitivity at 1 cpd appeared to be independent of age. The depth of focus for a
      4-mm pupil increased significantly with age, even though contrast sensitivity at
      +2 D defocus decreases with age too, but not as much as the contrast sensitivity
      at optimal focus. Our study indicates that the effect of defocus on contrast
      sensitivity decreases with age; this was attributed to age-related changes in the
      optical media.

PMID- 10962700
TI  - The calibration of a 2.5x Galilean focusable telescope as an optometer for
      refraction.
AB  - A 2.5x Selsi achromatic Galilean focusable telescope was calibrated for
      refraction at 6 m. In its calibration, minus power trial lens was placed at the
      objective of the telescope to simulate vergence of a target at a finite distance,
      before the back vertex power (BVP) of the telescope at each setting (telescope
      length) was measured by a focimeter. By using a graphical presentation of the
      results, the BVP of the telescope at each setting could be determined at
      different selected target distances. For a target vergence of -0.167 D or a
      distance of 6 m, the common testing distance in clinical practice, this
      calibrated telescope had a BVP or refraction measuring range of -7.27(-)+7.52 D.
      When this telescope was used to measure simulated manifest refractive errors at 6
      m, it yielded a mean error of +0.13 D with a 95% confidence limit of agreement of
      -0.38(-)+0.64 D. These results indicated that the accuracy and precision of
      telescopic refraction were comparable to that of retinoscopy. Therefore, the
      calibrated telescope could be considered as a reliable and inexpensive instrument
      for determining spherical refractive errors. Telescopic refraction is applicable
      in refracting economically disadvantaged population in underserved areas where
      modern equipment and electricity are not available. In addition, it provides an
      alternative subjective refraction method for low vision population because the
      magnification of this calibrated telescope has the advantage of allowing low
      vision patients to be refracted at the common 6 m testing distance in clinical
      practice.

PMID- 10962701
TI  - Risk and protective factors influencing adolescent problem behavior: a
      multivariate latent growth curve analysis.
AB  - This study examined the dynamic relations between adolescent problem behaviors
      (alcohol, marijuana, deviance, academic failure) over time and predictors of
      these behaviors. Data from the National Youth Survey (1) included 1,044
      adolescents (53.5% male; mean age at year 1 = 13.20). Dependent measures were
      adolescent alcohol use, marijuana use, deviance, and academic failure, assessed
      annually over 4 years. Independent measures included age, gender, marital status,
      income, family time, family support, time with friends, friend deviance,
      knowledge of friends, activities, and neighborhood problems. An associative
      latent growth modeling (LGM) analysis showed significant increases and relations
      between the four behaviors in both initial status and development. Second-order
      multivariate LGM analyses indicated that the four behaviors could be modeled by a
      higher-order problem behavior construct. Significant effects on the common
      problem behavior intercept or slope included time with friends, deviant friends,
      age, marital status, family time, and support. Additional effects were found to
      be specific to the initial status and slopes of individual problem behaviors.
      Overall, results indicate the importance of assessing the relations between
      adolescent problem behaviors as they change over time and identifying the risk
      and protective factors that have both common and individual influences on these
      behaviors.

PMID- 10962703
TI  - Sleep apnea and health-related quality of life in African-American elderly.
AB  - The relationship between health-related quality of life (HRQOL) and sleep apnea
      was examined in a sample of elderly African-Americans screened for snoring and
      daytime sleepiness. Seventy African-Americans over the age of 65 years completed
      a comprehensive sleep questionnaire, the Quality of Well-Being Scale (QWB), and
      the Medical Outcomes Study (MOS) Core Measures of HRQOL (116-item Long Version)
      and had sleep recorded. Those with moderate-severe sleep apnea had significantly
      lower Physical Component summary scores than those with no sleep apnea (p <
      0.05). After controlling for medical conditions, sleep apnea was significantly
      related to both general physical functioning and general mental health
      functioning in those with mild apnea (apnea-hypopnea index [AHI] < 15), but not
      in those with moderate to severe apnea. There was an initial decrease in HRQOL up
      to an AHI level of 15, at which point HRQOL remained at a lowered level. The QWB
      scores of our sleep apnea sample were similar to the QWB scores found in patients
      with depression and chronic obstructive pulmonary disease (COPD), suggesting that
      sleep disturbances may impact daily living and health as much as other medical
      conditions.

PMID- 10962702
TI  - Impact of gender and having children in the household on ambulatory blood
      pressure in work and nonwork settings: a partial replication and new findings.
AB  - Ambulatory blood pressure (ABP) has been shown to differ for men and women across
      work and nonwork settings. For men, ABP is higher at work than at home on
      workdays or on nonworkdays. For women, ABP levels in different settings depend on
      whether they have children in the household. Women without children at home
      exhibit the "male" pattern of higher ABP at work than at home. Women with
      children at home show either similar ABP levels in the two locations or higher
      ABP at home. These different patterns have been assumed to represent different
      stress levels in the two locations, but this assumption has rarely been tested.
      Also, few studies have examined ABP levels on a nonworkday in women or the effect
      of having children in the household for men. The present study monitored ABP in
      men and women during two workdays and one nonworkday. Comparisons were made
      between ABP levels in three settings (workday at work, workday at home,
      nonworkday) using mixed random effects regression models. Psychosocial variables
      (e.g. mood, stress) that might mediate the different ABP patterns were also
      assessed. ABP differences were analyzed by gender and whether children were
      living in the household using mixed random effects regression models. Results
      indicated that diastolic blood pressure was higher at work versus home for men
      with children and higher at work and on nonworkdays than at home for women
      without children. ABP did not differ across settings for women with children or
      men without children. These results were not mediated by mood or stress levels in
      the three settings.

PMID- 10962704
TI  - Patient expectations as predictor of chemotherapy-induced nausea.
AB  - We examined the relationship between patients' pretreatment expectations for
      nausea and vomiting and their subsequent development in a homogeneous group of 29
      female cancer patients receiving platinum-containing chemotherapy as inpatients
      (Study 1) and in 81 subjects with any of a variety of cancer diagnoses treated
      largely as outpatients (Study 2). Each study found a significant relationship
      between patients' expectations for nausea development measured prior to their
      first treatment and their mean postchemotherapy nausea severity (both, p < 0.05).
      Patients' expectations accounted for unique variance in nausea severity in each
      study even after controlling for known pharmacological and physiological
      predictors of nausea (Study 1: delta R2 = .18, p < .04; Study 2: delta R2 = .05,
      p < .03). By contrast, we found no significant relationships between expectations
      for vomiting and subsequent vomiting. Our results support the view that patients'
      expectations for nausea affect its subsequent development, indicating the
      presence of a significant psychological component in treatment-related nausea.
      Implications of this are discussed.

PMID- 10962705
TI  - Optimism and depression as predictors of physical and mental health functioning:
      the Normative Aging Study.
AB  - Dispositional optimism has been linked in previous studies to better health
      outcomes. We sought to examine the independent associations of dispositional
      optimism and depressive symptoms with physical and mental functioning in a cohort
      of healthy middle-aged and older men. The study was conducted among 659 subjects
      in the Veterans Administration (VA) Normative Aging Study. Dispositional optimism
      and depressive symptomatology were measured in 1991 and 1990, respectively, by
      the Life Orientation Test and the Center for Epidemiologic Studies--Depression
      Scale (CES-D). The dependent variables, functioning and well-being, were measured
      in 1992 by the Medical Outcomes Study Short-Form Health Survey (SF-36). In
      multivariate regression models, optimism was associated with higher levels of
      general health perceptions, vitality, and mental health, and lower levels of
      bodily pain, but not to physical functioning, social functioning, or role
      limitations due to physical or emotional problems. Depressive symptomatology was
      associated with reduced levels of functioning across all SF-36 domains. The
      findings for optimism and depression were statistically significant after mutual
      adjustment in multivariate regression models. Optimism and depression are
      independent predictors of functional status among aging men.

PMID- 10962706
TI  - Physical activity, self-esteem, and self-efficacy relationships in older adults:
      a randomized controlled trial.
AB  - A randomized controlled trial examined the growth and form of multidimensional
      self-esteem over a 12-month period (6-month exercise intervention and 6-month
      follow-up) in 174 older adults engaged in either a walking or stretching/toning
      program. The extent to which changes in physical fitness parameters and physical
      self-efficacy were related to changes in perceptions of attractive body,
      strength, physical conditioning, and physical self-worth was also determined.
      Latent growth curve analyses showed a curvilinear pattern of growth in esteem
      with significant increases at all levels of self-esteem upon completion of the
      intervention followed by significant declines at 6 months postintervention in
      both groups. Frequency of activity and changes in physical fitness, body fat, and
      self-efficacy were related to improvements in esteem perceptions relative to
      attractive body, strength, and physical condition. Model fitting procedures
      suggested that the best fit of the data was to a model in which the influence of
      changes in efficacy and physical parameters on physical self-worth were mediated
      by perceptions of attractive body and physical condition.

PMID- 10962707
TI  - Autonomic and neuroendocrine responses to mild psychological stressors: effects
      of chronic stress on older women.
AB  - We investigated autonomic and endocrine responses to acute stressors in 27 women
      who were or are presently caring for a spouse with a progressive dementia (high
      chronic stress) and 37 noncaregivers who were category matched for age and family
      income (low chronic stress). Measures were taken before (low acute stress) and in
      response to brief laboratory stressors (high acute stress). We replicated prior
      research showing that caregivers report greater stress, depression, and
      loneliness than the comparison groups, and acute stressors elevate autonomic and
      neuroendocrine activity. We also found that caregivers, relative to
      noncaregivers, exhibited shorter preejection periods and elevated blood pressure
      and heart rate, but the magnitude of autonomic and neuroendocrine reactivity to
      the experimental stressors was comparable across these groups. This pattern of
      autonomic differentiation replicates prior research showing that caregivers are
      characterized by higher sympathetic activation than noncaregivers and suggests
      that the effects of chronic stress on physiological reactivity may be a less
      robust effect in older adults.

PMID- 10962709
TI  - Risk-resistance adaptation model for caregivers and their children with sickle
      cell syndromes.
AB  - This investigation examined the risk-resistance adaptation model for children
      with sickle cell disease and their primary caregivers. Participants were 55
      children, ranging in age from 5 to 16 years with a mean age of 9 years 2 months,
      diagnosed with sickle cell disease and their primary caregivers, recruited from a
      university medical center. Measures included adjustment (i.e. primary caregiver
      and child adjustment), risk factors (i.e. disease and disability, functional
      independence, and psychosocial stressors), resistance factors (i.e. intrapersonal
      health locus of control, social-ecological), and stress processing (coping).
      Primary caregivers' adjustment was associated with developmental coping, changeR2
      = .08, and child adaptation was associated with an internal health locus of
      control, changeR2 = .22. An indirect effect of primary caregivers' coping on
      child adjustment was found through influence on primary caregivers' adjustment,
      changeR2 = .11. The findings support research among other chronically ill
      populations that suggests an association between coping and disease adjustment.
      The results were interpreted to support the use of theoretically driven models in
      predicting the adaptation of children with chronic illness and adjustment in
      their caregivers.

PMID- 10962708
TI  - Depression and functioning in relation to health care use in sickle cell disease.
AB  - The purpose of the current study was to investigate depression and health care
      use in patients with sickle cell disease (SCD). Forty-four adults with SCD were
      interviewed and data from 43 participants, both with (n = 11) and without (n =
      32) depression, were used for further analyses. Data from one potential subject
      were excluded on the basis of diagnosis. The full evaluation included the
      Structured Clinical Interview for DSM-III-R Disorders (SCID) and the Center for
      Epidemiologic Studies--Depression Scale (CES-D), as well as measures of
      psychosocial and behavioral functioning. Good between-instrument agreement was
      found between the self-report and interview-based measures of depression.
      However, the functioning data did not entirely support the use of a more
      stringent cutoff score on the CES-D. Findings suggest that the purpose of the
      evaluation should be factored into the decision-making process when determining
      which cutoff score should be utilized (i.e. what is the cost-benefit ratio for
      false-positives vs. false-negatives). A series of hierarchical regression
      analyses supported the finding that disease severity alone does not explain the
      level of functioning displayed by patients. More importantly, the patient's
      perceived functioning was the best indicator of health care use within a 1-year
      period. Furthermore, specific interventions that target negative thinking and
      distorted cognitions, as well as provide psychoeducation, such as cognitive
      behavioral therapy, need to be further explored within this population.

PMID- 10962710
TI  - [Molecular genetic analysis for taxonomic determination of fossil skull fragments
      of Warendorf-Neuwarendorf].
AB  - The isolation and examination DNA segments from prehistoric and fossil bone
      samples has become one of the biggest challenges in anthropology within the past
      years. By using specially developed and/or adapted genetic methods, it is
      possible under laboratory conditions to amplify portions of DNA from bone remains
      in states of good preservation by the polymerase chain reaction (PCR). DNA
      sequence data can provide far more specific answers to palaeanthropological
      questions than one would expect solely by morphologic comparison. Here we
      introduce an alternative approach for the classification of total ancient DNA by
      means of Southern hybridisation techniques.

PMID- 10962711
TI  - A population genetic characterization of Estonians.
AB  - This paper discusses the genetic characterization of Estonians on the basis of
      eight blood group systems, and the traits of PTC tasting and colour blindness in
      40 Estonian population samples from various parts of the country. The allele
      frequencies for the total Estonian population and for the four most different
      regions are presented. The survey shows genetic heterogeneity within the
      Estonians; the greatest genetic differences were observed in West-East direction.
      The West-Islands, West, and North Estonia differ from the other regions (East,
      South-East, also South-West and Central Estonia--which form a compact cluster).
      The mean allele frequencies of the Estonians are comparable to those typical for
      populations from North and East Europe, but the allele frequencies of Estonians
      are characterized by tendencies in two opposite (western and eastern) directions,
      like in other Finno-Ugric populations and concerning other anthropological
      traits. Estonians reveal closest similarities to the nearest neighbouring
      populations, regardless of their language group. The genetic heterogeneity and
      antagonistic traits in Estonians seem to be traces of the original genetic
      structure of Finno-Ugric ancestor populations which were neither Mongoloid nor
      Caucasoid.

PMID- 10962712
TI  - [Hemogenetic studies of the Cologne political district (North Rhine-Westphalia,
      Germany)].
AB  - In two population samples from the administrative area of Cologne, North Rhine
      Westphalia, Germany (Eschweiler/Stolberg, B frequencies > 0.0800;
      Hurtgenwald/Inden/Langerwehe, B frequencies < 0.0800), 26 hemogenetic systems had
      been studied. The resulting differences of allele and haplotype frequencies,
      resp., are significant. These differences are interpreted as a result of the
      migration from North-East Europe to North Rhine-Westphalia in the last 120 years
      and the selective geographic distribution of the migrants in the industrial and
      urbanized areas.

PMID- 10962713
TI  - DNA-PCR systems TH01 and VWA31: population data from Albania and Romania.
AB  - The microsatellite systems TH01 and VWA31 have been typed and analyzed for three
      populations from Albania (city population of Tirana, and Aromuns from a small
      sized village, named Andon Poci, near Gjirokaster) and Romania (city population
      of Constanta). The genetic data have been compared with other, particularly South
      Eastern European population.

PMID- 10962714
TI  - Red cell enzyme polymorphisms in Friuli Venezia Giulia (northeast Italy).
AB  - Seven erythrocyte enzyme polymorphisms (ACP1, ADA, ESD, GLO1, PGD, PGM1 and PGM2)
      were investigated in a sample of 673 unrelated adult individuals from Friuli
      Venezia Giulia (or Friuli) and Istria. The gene frequencies found in the four
      provincial samples of Friuli and Istria fall within the range previously reported
      for Italy, showing a genetic homogeneity among the considered samples. However,
      comparisons with data from ex-Yugoslavian samples--using the chi 2 test--showed
      rather marked differences, probably due to a real different genetic structure of
      the compared samples. A significant association was found assuming a linear
      relation between the ADA*2 allele frequencies and longitude (r = +0.5503) and
      between the PGD*C frequencies and latitude (r = -0.6483), suggesting the
      existence of a clinal trend for these allele frequencies in Italy. These results
      seem to disagree with foregoing conclusions stated by other authors, probably
      because these studies were carried out in an area either rather narrow from the
      geographical point of view or affected by small size migration movements.

PMID- 10962715
TI  - Genetic polymorphism of group-specific component/vitamin-D-binding protein
      subtypes in six populations from north-eastern China.
AB  - On six populations from North-Eastern China the frequencies of Gc subtypes were
      studied by isoelectric focusing on ultra-thin polyacrylamidegel followed by the
      improved sulfosalicylic acid precipitation. The following Gc subtype allele
      frequencies could be observed in the Han (Harbin), Ewenki, Tahur, Mongolian,
      Oroquen and Xibe populations: Gc*1F = 0.4246, 0.4941, 0.4479, 0.4077, 0.4606 and
      0.4503; Gc*1S = 0.2587, 0.2936, 0.3151, 0.2822, 0.3370 and 0.3035; Gc*2 = 0.3065,
      0.2064, 0.2266, 0.3006, 0.2022 and 0.2388. In addition to this 16 individuals of
      five populations showed rare Gc variant alleles (1A3, 1A8, 1A9, 1A14, 1C?).

PMID- 10962716
TI  - Use of the hand bones roentgenographs in the prediction of age in nine human
      populations.
AB  - The major aim of this study was to develop an accurate method of age prediction
      for a wide range of ages, based on the roentgenographic assessment of the hand
      bones, for use in paleoanthropology and forensic medicine. The roentgenographs of
      the hand bones were assessed in 5756 individuals, 2683 males and 3073 females,
      aged 17-93 and 17-89, respectively, belonging to 9 ethnic groups from the former
      USSR, Israel, and Sinai peninsula (Egypt). For each roentgenogram an equidistant
      osteographic score (OSS) including the descriptive criteria of bone age, such as
      (1) osteophytes or nodes of Heberden in the periarticular regions and at sites of
      tendon attachment, (2) manifestations of osteoporosis, (3) signs of sclerosis,
      and (4) non-traumatic articular deformities, was estimated. Regression analysis,
      that included linear, non-linear, logistic, and stochastic models, was used to
      evaluate the relationships between age and OSS. This relationship was best
      described by a logistic regression function. Results of the logistic regression
      analysis clearly indicate that OSS is a strong predictor of an individual's age,
      with r2 values ranging from 0.671 to 0.901 (p < 0.001). Our standard errors of
      estimate were ranging from +/- 4.2 to +/- 7.3 years, comparing favorably with
      most known methods of bone age assessment. This study provides an efficient
      method of age prediction, which allows to extend the upper limit of prediction to
      the age of 70 years with acceptable accuracy.

PMID- 10962717
TI  - [The 1999 Nobel Prize for physiology or medicine].
AB  - It has been awarded to Gunter Blobel, for a so-called signal hypothesis. In this
      research Gunter Blobel has proven that information about the final localization
      of a protein in the cell is given in its sequence. Such a targeting signal can be
      either cut off (presequence) or can be localized within the final sequence of a
      protein. The mechanisms responsible for secretion, the movement of proteins to or
      from nucleus, and guiding of proteins to mitochondria, chloroplasts and
      peroxisomes have been described. In particular, proteins involved in interactions
      with the signal sequences were reviewed. The channels responsible for transfer of
      polipeptides through the membranes were also presented. A contribution of Gunter
      Blobel and his coworkers in the foundation and development of a new field of
      research on protein guidance has been emphasized.

PMID- 10962718
TI  - [Intima-media complex thickness of common carotid artery as a risk factor for
      stroke].
AB  - Intima-Media Thickness (IMT) of Common Carotid Artery (CCA) could be seen as the
      atherosclerotic risk factors' final morphological effect. We investigated the
      hypothesis that IMT of CCA is significantly different in sex- and age-matched
      groups of persons with stroke and healthy subjects. 47 patients with first-ever
      atherothrombotic stroke proven by CT were investigated. Patients with atrial
      fibrillation, valvular heart disease and left ventricular hyperthrophy were
      excluded. The IMT of CCA were estimated by High-Resolution B-Mode
      Ultrasonography. All the patients had bilateral IMT measurement within 20 mm
      proximal to the carotid bulb on the far wall in the anterioposterior and
      laterolateral plane. The results were compared with those obtained in 50 healthy
      sex- and age-matched subjects. We found a strong association between IMT and
      stroke (p < 0.0001). Mean IMT was 0.96 mm (SD 0.18) in patients and 0.70 mm (SD
      0.09) in controls. The presence of atherosclerotic plaques was 0.34 and 0.08 for
      patients and controls respectively (p = 0.0025). IMT of CCA is strongly
      positively associated with the risk for stroke. The frequency of atherosclerotic
      plaques in CCAs is statistically significantly higher in stroke patients than in
      control group.

PMID- 10962719
TI  - [The usefulness of the method of planar diffusion echo imaging (EPI DWI) in the
      diagnosis of cerebral ischemia].
AB  - The preliminary results of MR echoplanar diffusion-weighted imaging (EPI DWI) in
      patients with stroke are presented. Twelve patients (5 females, 7 males) aged 36
      78 years (mean 63.8) were examined by 2T system. No focal lesions were found in
      the acute phase of stroke on T1-weighted images. Narrowing of sulci in the region
      of stroke was the only abnormal finding. Focal hyperintense lesions were shown on
      PD and T2-weighted images in 50% of patients in the acute phase, 7 hours after
      the onset of clinical symptoms. On EPI diffusion-weighted images focal decrease
      of apparent diffusion coefficient (ADC) was observed in all cases of the acute
      phase of stroke after 3 hours. EPI DWI allows for earliest detection of ischaemic
      lesions in brain tissue. The method is especially useful in characterisation of
      the acute phase of stroke and shows its evolution thanks to the use of ADC.

PMID- 10962720
TI  - [The application of dysarthria profile tests in ALS patients for the detection of
      speech disturbances].
AB  - Dysarthria is an invalidating disability in ALS patients with motor neuron
      degeneration in the bulbar region. The methods to assess dysarthric disorders in
      ALS are seldom described in publications. This study was performed in 43 patients
      who had definite (n = 23) or probable (n = 20) ALS (of the bulbar group n = 15,
      of the limb group n = 28, mean age = 57.07 (range: 36-69 yr.)) according to WFN
      criteria. The method based on quantitative tests of dysarthria profile (by
      Robertson, 1986) was used and the results were compared with 37 age, sex-matched,
      healthy control subjects. Our study showed the existence of disturbances in all
      dysarthria profile tests which were of the statistic significance and more
      frequent as compared to the control subjects (p < 0.01). The analysis showed that
      quantitative assessment of some dysarthria profile tests (5 out of 8) might be
      useful in clinical practice to detect dysarthria in ALS patients. Using the
      dysarthria profile tests we also demonstrated that preclinical dysarthric
      processes occur among the limb ALS group.

PMID- 10962721
TI  - [The effect of cladribine treatment on beta-2 microglobin in the cerebrospinal
      fluid and serum of patients with multiple sclerosis].
AB  - Multiple sclerosis (MS) is the most frequent demyelinating disease of the central
      nervous system (CNS). Lymphocytes seem to play a crucial role in the pathogenesis
      of the disorder. They are rich in, among others, beta-2Microglobulin (beta 2M)--a
      low molecular weight protein located extracellularly and associated with class 1
      antigens of the major histocompatibility complex. beta-2M is considered as a
      marker for disease activity in immune disorders. Its precise role in pathology
      remains still unknown, but there is evidence that it may be involved in
      lymphocyte activation. Cladribine (2-chloro-2-deoxyadenosine, 2-CDA) is a potent
      lymphocytotoxic agent under investigation in the treatment in MS patients,
      earlier used in hairy-cell-leukemia therapy. Previous studies in MS populations
      showed beta 2-microglobulin to be moderately increased. Suspecting that beta 2M
      levels might indicate inflammatory events in CNS we determined CSF-beta 2M and
      serum beta 2M concentration in patients with relapsing-remitting MS (n = 15)
      before and after cladribine treatment as well as in a control group diagnosed as
      tension type headache (n = 10). There was a significant decrease in the CSF and
      sera beta 2M level in MS patients after cladribine treatment, associated with a
      slight but significant clinical improvement measured by Kurtzke's Expanded
      Disability Status Scale. We conclude that beta 2M is a sensitive marker of the
      CDA influence on the immune system in MS patients; however, increase in CSF and
      sera beta 2M is not specific as there was no statistically significant difference
      between MS and control patients.

PMID- 10962722
TI  - [Assessment of cerebrovascular reserve capacity in patients with carotid artery
      disease using transcranial Doppler sonography and acetazolamide].
AB  - AIM: In our study we utilised transcranial Doppler sonography (TCD) and the test
      with intravenously administered acetazolamide (reversible inhibitor of carbonic
      anhydrase) which causes vasodilatation of the brain resistance vessels to assess
      cerebrovascular reserve capacity (CVRC) in patients with symptomatic and
      asymptomatic carotid stenosis. MATERIAL: 25 patients (22 male, 3 female; aged 46
      82; mean 62 years) with carotid artery disease were examined. They were qualified
      for the operation because of that. METHOD: Blood flow wave spectrum in the right
      and left middle cerebral artery (MCA) was analysed. 2 MHz pulsed-wave transducer
      was placed over the appropriate temporal acoustic window. We measured mean blood
      flow velocity (Vmean) in both MCAs. The records were taken: a) at rest, b) 15
      minutes after 1.0 g of acetazolamide was administered intravenously.
      Cerebrovascular reserve (CVRC) was calculated as the maximal percentage increase
      in the appropriate MCA after the administration of acetazolamide in comparison
      with its value at rest. The values of CVRC were analysed statistically. RESULTS:
      15 minutes after acetazolamide was injected CVRC was 44 +/- 15% (mean +/- SD)
      (range 0-74) in asymptomatic hemispheres. In 30 patients (97%) CVRC was 46 +/-
      12% (23-74) and in 1 patient (3%) 0% (case nr 7). In the group of symptomatic
      hemispheres CVRC was 12 +/- 15% (-16-36) after acetazolamide administration. In
      12 patients (63%) from this group CVRC was positive: 20 +/- 11% (3-33), in 4
      patients (21%) CVRC was 0% (cases nr 8, 9, 22, 23) and in other 3 patients (16%)
      CVRC was negative: -7 +/- 8 (-16(-)-3) (cases nr 4, 12, 19). CONCLUSION: 1. The
      group of patients with symptomatic hemispheres have statistically lower CVRC in
      comparison with the group of asymptomatic hemispheres. 2. There was no
      statistical difference between the mean values of CVRC in patients with
      bilateral, severe carotid stenosis and the ones with unilateral changes. 3. We
      believe that such a test performed by means of TCD and intravenously injected
      acetazolamide can indicate a subgroup of patients with carotid stenosis for whom
      carotid endarterectomy is necessary at the earliest time because of possible
      early neurological complications appearance which are related to the lack or
      serious impairment of CVRC.

PMID- 10962723
TI  - [The influence of radiation doses on the results of radiosurgery of brain
      arteriovenous malformations].
AB  - Stereotactic radiosurgery as a method of treatment of inoperable brain angiomas
      has been in use in the Neurosurgery Department, Medical Academy in Lublin since
      1990. The patients receive radiation from a Neptune 10P linear accelerator of 9
      MeV photon energy (X radiation). The Laitinen stereoadapter used by us makes
      possible precise targeting and radiation application in time suitable for the
      patient and the whole treatment team. This frame produces no disturbances of CT
      image and is not covering the target. Non-invasive head immobilization in the
      frame is highly stable, although it requires good communication with the patient
      and his full cooperation. The purpose of the study was a comparison of the
      results of radiosurgery applied in the treatment of inoperable brain angiomas of
      various size with radiation doses 4000 cGy and 3000 cGy. The material comprises
      40 first cases out of over 120 patients treated in this way for inoperable
      angiomas. The first group of 20 patients received 4000 cGy and the second group
      of 20 patients received 3000 cGy doses. Complete obliteration of angiomas was
      achieved in 16 (80%) cases treated with the 4000 cGy dose, and in 17 (85%) cases
      treated with the 3000 cGy dose. Late postradiation reactions developed in 15
      (75%) patients in the first group with permanent changes in 5 (25%) patients. In
      the second group late postradiation reactions developed in only 6 (30%) cases and
      regressed in all. Treatment effectiveness (complete obliteration) after doses of
      3000 and 4000 cGy was similar, and it decreased with greater size of angiomas.
      The per cent of postradiation complications after lower doses was much smaller,
      and permanent neurological changes were seen only after higher doses. The
      obtained results of the method are comparable with those of the authors using
      invasive methods of fixation of stereotactic frames.

PMID- 10962724
TI  - [Lipid image in glioblastoma multiforme].
AB  - Changes in the content and composition of lipids in brain tumours of different
      degree of malignancy are still the subject of numerous scientific studies. It is
      known that in developing brain tumours structural and functional changes of its
      cells, take place, in which lipids play a crucial role. The examination of the
      lipid spectrum was conducted in a material extracted from tumour adjacent areas
      (by means of fenestration) as well as from tumours themselves in 11 patients
      (mean age 56.8 yrs). Based on histological studies all the tumours were qualified
      as glioblastoma 4th degree of malignancy. Lipids were isolated from the tumours
      as well as from their adjacent areas. Later on they were separated, using column
      chromatography and thin-layer chromatography, into three classes: phospholipids,
      galactolipids and neutral lipids. Separated lipids were subjected to quantitative
      analysis by spectrophotocolorimetric method. In comparison to adjacent areas, in
      tumours distinct changes of lipid levels were noticed in all analysed lipid
      classes. Statistical analysis showed significant decrease of phospholipids
      (elements stabilizing cell membranes) in tumours in comparison to their adjacent
      areas (Wilcoxon's test: p < 0.05). At the same time in tumours an increase of
      level of plasmalogens took place: phosphatidylcholine (PC) (PPC),
      phosphatidylethanolamine (PE) (PPE) typical elements of malignant tumours,
      responsible for cross cell membrane transportation processes. This phenomenon was
      accompanied by changes of levels of PC/PE and PC/SM (sphingomyelin) ratios
      connected with adhesiveness and other membrane features. Changes in the level of
      lipids, and phospholipids in particular, in glioblastoma 4th degree of malignancy
      in comparison to adjacent areas can indicate the pathological processes in cells
      of these tumours.

PMID- 10962725
TI  - [Cryopallidotomy in Parkinson disease. Effect on somatosensory potentials].
AB  - The paper reports 4-years results of a pilot study concerning the influence of a
      stereotactic pallidotomy on somatosensory evoked potentials in idiopathic
      Parkinson's disease. Potentials were recorded through the scalp surface from
      sensorimotor cortex of both hemispheres. Amplitudes and latencies of early and
      late waves were compared before and after the surgery. The surgery was
      recommended after 4 years of L-dopa therapy when bradykinesia and rigidity of
      right leg led to gait difficulty and postural instability. The dominant features
      of the syndrome were accompanied by tremor, micrography, chorea and lower
      responsiveness to L-dopa. Following the surgery a clear improvement of motor
      activity was observed. Increase of 20-90 ms waves amplitudes and P45 latency
      prolongation of 6-11 ms appeared due to the attenuation of pallidal inhibition
      exerted upon the thalamo-cortical transmission and a new arrangement of a
      cortical motor program. These electrophysiological changes, correlated with a
      clinical amelioration, may indicate as a favourable prognosis for a patient. Five
      months after pallidotomy a slight decrease of amplitudes occurred in relation to
      the previous examinations. Four years after surgery increase of most amplitudes
      and latencies and reconfiguration of later waves were related to deterioration of
      clinical course and worsening of left-side signs. We believe that somatosensory
      evoked potentials change may be a sensible indicator of motor state in
      Parkinson's disease. As far as we know the present study is one of the first
      presentation of somatosensory evoked potentials after pallidotomy.

PMID- 10962726
TI  - [Myositis specific autoantibodies as a new diagnostic criterion for idiopathic
      inflammatory myopathies].
AB  - Myositis specific autoantibodies (MSA) are the most specific diagnostic criteria
      for idiopathic inflammatory myopathies (IIM). There is no evidence of MSA
      presence in patients with other neuromuscular or connective tissue diseases. MSA
      are associated with homogeneous clinical syndromes: antisynthetases with
      antisynthetase syndrome, anti-SRP with severe, resistant to treatment myositis,
      anti-Mi-2 with classic, benign dermatomyositis. Therefore it is important to
      include the myositis specific antibodies into routine diagnostic scheme of IIM.

PMID- 10962727
TI  - [Coexistence of intrathecal immunoglobulin synthesis with amyloidosis in patient
      with polyneuropathy in the course of multiple myeloma].
AB  - A coexistence of high level of intrathecal monoclonal immunoglobulin (intrathecal
      synthesis?) and amyloidosis as a possible cause of peripheral neuropathy in
      multiple myeloma patient was presented. In the reported case neurological
      symptoms and intrathecal monoclonal protein existence had been manifested several
      months before the appearance of plasmocytoma.

PMID- 10962728
TI  - [Thoracic spine meningioma mimicking intramedullary tumor].
AB  - This report presents a case of a meningioma of the thoracic spine with a wide
      range of symptoms in a 23-year-old woman. The factor, which was making difficult
      the proper diagnosis, was atypical for a meningioma MRI--scan, mimicking
      intramedullary tumour. The tumour was removed radically with a favourable
      clinical outcome. Clinical history, surgical treatment and neuropathologic
      findings are described. A review of pertinent literature is included.

PMID- 10962729
TI  - [Anterior interbody fusion of cervical spine with BAK-C: case reports].
AB  - Two cases of cervical discopathy operated on with anterior interbody fusion with
      the BAK-cage are described. The authors stress the advantages of this kind of
      stabilization: shorter time of the operation, no bone graft complication,
      immediate stabilization without collar. The technical procedures of BAK-cage
      implantation, indications and exclusion criteria are discussed.

PMID- 10962730
TI  - [CADASIL].

PMID- 10962731
TI  - [Letter concerning the paper published in Neur. Neurochir. Pol. in 1999, 33 (49),
      No. 4, p. 971-83 "Familial fetal angioma"].

PMID- 10962732
TI  - [Obituary on Zbigniew Bojarski, MD (1926-1999)].

PMID- 10962733
TI  - [The cerebral cortex: structure, interrelations of neurons, functional columnar
      organization].
AB  - The cerebral cortex develops from a portion of the telencephalic vesicle. Cells
      originating from the germinal zone surrounding the lumen migrate peripherally to
      form the cortical mantle. During the fetal life, cortical neurons begin to form
      six horizontal layers. Cells formed at the same time migrate to the same cortical
      layer, cells migrating later pass through deep layers to form more superficial
      laminae. A six layer cellular organization is characteristic of the entire
      neopallium, which is referred to as the neocortex. The paleopallium--olfactory
      cortex--and the archipallium--hippocampal formation and dentate gyrus--have three
      basic layers and collectively constitute the allocortex. Through the course of
      evolution, the cerebral cortex has increased enormously in surface area but not
      in thickness, a trend that can be seen even in the relatively short period of
      primate evolution. The human cortex is only about 15% thicker than that of the
      macaque monkey but is at least 10 times greater in area. To understand how this
      complex structure functions we need to examine its unique internal cellular
      arrangement.

PMID- 10962734
TI  - [Synaptic plasticity and neuromodulation of local cortical connections].
AB  - Long-term potentiation (LTP) and long-term depression (LTD) represent two forms
      of synaptic plasticity which may act as mechanisms for reorganizations of adult
      mammalian motor cortex. Layer II/III horizontal connections may form a substrate
      for these reorganizations. The induction of LTP in these connections requires
      conjoint activation of cortical layer V or layer I. The activity of the
      cholinergic system facilitates LTP induction.

PMID- 10962735
TI  - Neural mechanisms of visual feature grouping.
AB  - The present work relates compositions of visual scenes to signals in visual
      cortex and to cortical circuit models in order to understand neural mechanisms of
      perceptual feature grouping. It starts from the hypothesis that synchronization
      and decoupling of cortical gamma-activities (35-90 Hz) define the relations among
      visual objects. Here we concentrate on synchronization related to two basic
      visual situations, (1.) static retinal stimulation during ocular fixation, and
      (2.) transient stimulation during sudden luminance modulations or shifts in
      object position. For testing the synchronization hypothesis we investigated
      signal correlations of multiple micro-electrode recordings in visual cortex areas
      V1 and V2 of behaving monkeys. Static retinal stimuli induce gamma-activities
      that are loosely phase-coupled among neighboring neural populations of an
      object's cortical representation. This can explain why synchronization, measured
      by spectral coherence, is restricted to few millimeters cortex. Such patches of
      gamma-synchronization become de-coupled across the representation of an object's
      contour, and thereby can code figure-ground segregation. Transient stimuli evoke
      synchronized volleys of stimulus-locked activities that are typically non
      rhythmic and include low frequency components in addition to those in the gamma
      range. It is argued why stimulus-induced and stimulus-locked phase-coupled
      activations are both appropriate for supporting perceptual feature grouping.
      Clues for basic neural mechanisms participating in feature grouping are provided
      by our biologically motivated simulations of synchronization in cortical
      structures. (1.) Local populations generate gamma-oscillations via feedback
      inhibition during states of static retinal stimulation. (2.) Bidirectional
      facilitatory connections serve for phase-coupling among neighboring neural
      populations. (3.) Spike transmission delays, increasing with cortical distance,
      can explain the restriction of gamma-coherence to patches of few millimeters
      cortex. (4.) The size of synchronization patches in one visual area (e.g., V1)
      can define the size of classical receptive fields at the consecutive level of
      visual processing (V2) if Hebbian learning is operative. This may explain the
      increase in receptive field size at consecutive levels of visual processing. In
      conclusion, our results and those of others are supportive for the hypothesis
      that phase-coupled gamma-signals can code feature grouping and object continuity.
      However, convincing experimental proofs showing directly the dependence of
      perceptual grouping on cortical phase-coupling are still lacking.

PMID- 10962736
TI  - [Localization of attention related cortical structures by evoked potentials].
AB  - Attention is an ambiguous concept, difficult to direct implementation in
      neurophysiological studies. The paper presents application of the Continuous
      Attention Test (CAT) items as stimuli in event related potential (ERP) studies on
      attention. Stimuli with high demand of attention result in enlarged N1 component
      in occipital derivations. Spatial analysis revealed increased positivity in
      frontal derivations. Three-dimensional image of cortical current density by means
      of Low Resolution Electromagnetic Tomography (LORETA) revealed sources of N1
      component in occipital, parietal and postero-temporal derivations with the
      maximal current value at 17 Brodmann area. After target stimuli increase of
      current density in frontal derivations was observed, with the maximal value in
      the left 9 Brodmann area.

PMID- 10962737
TI  - Nonlinear mechanisms of cortical oscillations.
AB  - Not only theoretical consideration but also analyses of MEG or EEG recordings
      prove the nonlinear character of cortical dynamics. For instance, an averaged
      local Lyapunov Exponents (ILE) have positive value that is characteristic for
      chaotic dynamics. Also a test for nonlinearity (or determinism)--so called
      surrogate data test distinguishes between original- and randomized-phase time
      series proving that recorded signals are nonlinear. These facts are a very strong
      experimental evidence to support the hypothesis that brain oscillators are
      governed by the deterministic, nonlinear, low-dimensional dynamics. The
      experimental manifestations of nonlinear cortical oscillations in the healthy and
      pathologically altered human brain and their deterministic character seems to be
      an important step in the understanding brain dynamics in the language of
      nonlinear systems theory. Clinical application may use nonlinear measures
      (especially ILE, and PD2i) for classification of pathologies and rough
      localization of the functional disturbance in the brain.

PMID- 10962738
TI  - [Consciousness and models of brain dynamics].
AB  - Consciousness is connected with attention, working memory and perception. The
      stream of consciousness contains only those elements that are present in the
      working memory. Neurophysiological correlates of conscious states are sought in
      form of synchronization processes based on 40 Hz oscillations needed to solve the
      binding problem. Alternative theories to solve or avoid the binding problem are
      presented. Correlates based on neural complexity index recently introduced by
      Tonioni and Edelman are especially promising. Theories of "activity bubbles" and
      of adaptive resonance explain many aspects of the conscious' experience
      phenomenology. Arguments supporting the idea that consciousness is a process of
      discrimination of continuous, non-symbolic representations appearing in small
      capacity working memory are presented. These representations create resonant
      states with long-term memory traces, a process that cannot be captured by digital
      computer simulations.

PMID- 10962739
TI  - Whither physiologic pacing? Implications of CTOPP.

PMID- 10962740
TI  - Pacemaker indication revisionism.

PMID- 10962741
TI  - Influence of propafenone on resetting and termination of canine atrial flutter.
AB  - Previous studies on atrial flutter (AF) presumed that resetting was due to the
      prematurity effect (PE) in which the stimulated antegrade wavefront travels in
      the tail of the AF preexisting wavefront. We studied the collision effect (CE)
      between the AF and the stimulated retrograde wavefronts, its contribution to
      resetting, and its relationship to AF termination and how they are affected by
      the Class IC agent propafenone (PPF). A canine model of AF was created using a Y
      shaped lesion in the right atrium in 14 dogs (33 +/- 3 kg). Five atrial bipolar
      electrodes were positioned around the tricuspid valve. In a subsequent set of 11
      dogs, we used 16 bipolar electrodes for recording. AF was induced by burst
      pacing. Single and multiple stimuli were applied to measure conduction time and
      reset-response curves (RRCs). This was repeated after the administration of PPF
      (1 mg/kg loading dose for 10 minutes, followed by 1.8 mg/kg/per hour infusion).
      Three distinct mechanisms were found to contribute to the RRC: the PE, the CE,
      and heterogeneity. PPF stabilized the RRC, increased significantly the cycle
      length (CL), the duration of the effective refractory period, as well as the
      duration of the excitable gap. However, PPF did not alter the duration of the
      fully excitable portion. We studied 36 annihilations without and 48 with PPF.
      Transient fibrillation was found in 75% of the episodes without, compared to 22%
      with PPF. Other types of termination such as conduction block, CL oscillations,
      and reversal of activation were found for 25% of the episodes without and 78%
      with PPF. In many cases, conduction block and CL oscillations were associated
      with a failure of propagation of the stimulated antegrade wavefront in the region
      of collision. Termination by reversal of activation suggests that propagation was
      two dimensional and could not be represented by a one dimensional movement. The
      average coupling interval (in percent of CL), that induced fibrillation was not
      significantly different from that at which conduction block occurred. This
      suggests that transient fibrillation is associated with a weak CE rather than
      with rapid pacing. The CE is amplified by multiple stimuli and PPF. The incidence
      of transient fibrillation in AF annihilation diminishes with PPF as the CE
      becomes more important. This suggests that the evaluation of PE and CE in AF may
      be an indication of the risk of atrial fibrillation.

PMID- 10962743
TI  - Three-year follow-up of atrial sensing efficacy in children and adults with a
      single lead VDD pacing system.
AB  - The purpose of this study was to evaluate the efficacy of atrial sensing in
      children with a single pass lead VDD pacing system and to compare it with the
      efficacy of atrial sensing in adult patients with the same pacing system.
      Although the feasibility of single pass lead VDD pacing system implantation in
      children was recently demonstrated, the efficacy of atrial sensing remains
      unclear. In addition, the effect of accelerated growth of children on the
      systems' efficacy has not been addressed. Atrial sensing followed by ventricular
      sensing and atrial sensing followed by ventricular pacing was prospectively
      evaluated in 13 children (age 0.5-15 years) and 24 adult patients (age 19-74
      years). All had the same endocardial pacing system using a single pass lead. The
      children and adults had effective atrial sensing at a success rate of 94.00 +/-
      9.687% and 96.04 +/- 4.64%, respectively, during mean follow-up of 3.5 years. The
      atrial electrogram amplitude was similar in both groups, 1.8 +/- 1.5 mV in
      children and 1.8 +/- 1.1 mV in adults. The adult patients more frequently
      exhibited ventricular sensing following atrial sensing. The ventricular pacing
      threshold and impedance were stable in both groups. When necessary, in children,
      the atrial sensing was corrected by adjusting the pacemaker's lower rate
      programming. Highly effective atrial sensing was demonstrated in children and
      adult patients with a single pass lead VDD pacing system. During a mean follow-up
      of 3.5 years, not only was the atrial electrogram amplitude stable, but the
      clinically relevant atrial sensing was highly effective, justifying endocardial
      pacing with single pass lead VDD pacing in children and adults with preserved
      sinus node function.

PMID- 10962742
TI  - Nonsustained, asymptomatic ventricular tachycardia in patients with coronary
      artery disease: prognosis and incidence of sudden death of patients who are
      noninducible by electrophysiological testing.
AB  - The objective of this study was to determine the long-term prognosis and the
      sudden death risk for patients with coronary artery disease and spontaneous
      nonsustained ventricular tachycardia who are not inducible by
      electrophysiological testing. Patients with coronary artery disease (CAD) who
      have spontaneous or inducible sustained ventricular tachycardia (VT) by
      electrophysiological testing are at increased risk of dying suddenly, and
      noninducibility is often considered as a favorable prognostic factor in their
      risk assessment. We studied 120 consecutive patients with CAD and nonsustained VT
      during Holter monitoring and followed the patients who were noninducible (n = 93)
      for 3.5 +/- 1.6 years. None of these patients received antiarrhythmic therapy
      except beta-blockade. Overall mortality and the sudden death risk was assessed by
      the Kaplan-Meier estimation. Predictors for overall mortality and sudden death
      were determined by multivariate analysis. During follow-up, 23 of the 93 patients
      died, including 13 suddenly. Overall mortality was 9% after 1 year, 16% after 2
      years, and 21% after 3 years, respectively. The incidence of sudden death was 1%
      after 1 year, 8% after 2 years, and 13% after 3 years, respectively. Patients
      with a LVEF < or = 0.35 had an increased overall mortality risk with 15% after 1
      year, 29% after 2 years, and 34% after 3 years (P = 0.012) and a risk of dying
      suddenly of 4% after 1 year, 12% after 2 years, and 18% after 3 years (P = NS),
      respectively. LVEF was the only independent predictor for overall mortality. In
      conclusion, patients with coronary artery disease and nonsustained ventricular
      tachycardia who are not inducible by electrophysiological testing have a moderate
      long-term overall mortality risk. The risk of dying suddenly in this patient
      group is small but not negligible, especially in patients with impaired LVEF.

PMID- 10962744
TI  - No gender differences in pacemaker selection in patients undergoing their first
      implantation.
AB  - Recent studies have indicated that women were less likely to receive
      sophisticated pacemaker devices than men. These differences could not be fully
      explained by demographic and clinical variables. The purpose of the present study
      was to assess whether a gender related difference might exist in pacemaker mode
      selection in patients undergoing their first implantation in The Netherlands.
      Records of first implants (n = 39,217) collected from 1988 through 1997 covering
      95% of all implantations in The Netherlands. From this population 33,564 (85.6%)
      patients were included for final analysis. We observed no significant sex
      differences in pacemaker selection in patients with atrioventricular conduction
      disorders and bundle branch block. In patients with sick sinus syndrome, only
      very old women (> or = 85 years) had more atrial systems implanted than men of
      similar age (6.5% vs 3.5%), whereas men received more double chamber pacemakers
      (12.3% vs 10.3%) (P = 0.002). However, the relative distribution of physiological
      versus nonphysiological pacemakers in this subgroup was similar for men and
      women. In patients with chronic atrial fibrillation/flutter associated with
      bradycardia, sex differences were only apparent in the age group of 75-85 years;
      women received more dual chamber pacemakers (8.8% vs 5.3%) whereas men received
      more single chamber ventricular pacemakers (94.2% vs 89.8%) (P = 0.0011). With
      increasing age, sex differences in pacemaker selection were absent, but there was
      a considerable drop in implantation rate of dual chamber systems. Our study
      showed no major sex differences in the selection of pacemaker devices. Physicians
      select pacemaker devices by age rather than gender, which might be a rational
      choice.

PMID- 10962745
TI  - Electrophysiological control of ventricular rate during atrial fibrillation.
AB  - Thirteen anesthetized canine subjects (17-29 kg) were used to demonstrate that
      mild cervical left vagal stimulation could control ventricular rate effectively
      during atrial fibrillation (AF). Two studies are presented. The first study used
      six subjects to demonstrate the inverse relationship between (manually applied)
      left vagal stimulation and ventricular excitation (R wave) rate during AF. As
      left vagal stimulation frequency was increased, ventricular excitation rate
      decreased. In these studies, a left vagal stimulus frequency of 0-10 per second
      reduced the ventricular excitation rate from > 200/min to < 50/min. The
      decreasing ventricular excitation rate with increasing left vagal stimulation
      frequency was universal, occurring in all 26 trials with the six subjects. This
      fundamental principle was used to construct an automatic controller for use in
      the second study, in which seven subjects were used to demonstrate that
      ventricular rate can be brought to and maintained within a targeted range with
      the use of an automatic (closed-loop) controller. A 45-minute record of automatic
      ventricular rate control is presented. Similar records were obtained in all seven
      subjects.

PMID- 10962746
TI  - Comparison of mid-term clinical experience with steroid-eluting active and
      passive fixation ventricular electrodes in children.
AB  - Although active fixation ventricular leads seem to have advantages over passive
      fixation leads, this study compares the follow-up results of active and passive
      fixation leads in children. We evaluated the implantation and follow-up data of
      41 children with active (Accufix II DEC, group 1) (n = 20) or passive (Membrane
      E, group 2) (n = 21) fixation, steroid-eluting ventricular leads. All but one of
      the patients in group 1 completed the 12-month follow-up. The mean follow-up
      period in group 2 was 10.4 +/- 2.9 months (range 3-12 months, median 12 months).
      In both groups the mean pacing threshold was measured as 0.51 +/- 0.09 V versus
      0.48 +/- 0.15 V (P > 0.05) at 0.5-ms pulse width, mean R wave amplitude as 9.9 +/
      2.5 mV versus 9.4 +/- 3.2 mV (P > 0.05), and mean impedance as 557 +/- 92 omega
      versus 664 +/- 160 omega (P < 0.05), respectively, at implantation. After the
      first week of pacing, mean threshold values in group 1 were significantly lower
      than those of group 2 (P < 0.01 and P < 0.05, respectively). During the follow-up
      period, lead impedance measurements did not show a significant difference between
      the two groups. In one patient from group 1, the lead (by unscrewing) was removed
      easily because of pacemaker pocket infection. No lead dislodgement or helix
      deformation occurred in group 1. Nevertheless, in one patient from group 2, the
      lead was extracted at 4-month postimplantation because of lead displacement. We
      conclude that the steroid-eluting active fixation lead (Accufix II DEC) have
      advantages of easier implantation and lower acute and chronic stimulation
      thresholds compared to the passive fixation lead (Membrane E). Therefore, Accufix
      II DEC is superior to Membrane E, and it is a better first choice in children
      with an implanted single chamber ventricular pacemaker.

PMID- 10962747
TI  - Hemodynamically optimized temporary cardiac pacing after surgery for congenital
      heart defects.
AB  - Disturbance of normal AV synchrony and dyssynchronous ventricular contraction may
      be deleterious in patients with otherwise compromised hemodynamics. This study
      evaluated the effect of hemodynamically optimized temporary dual chamber pacing
      in patients after surgery for congenital heart disease. Pacing was performed in
      23 children aged 5 days to 7.7 years (median 7.3 months) with various
      postoperative dysrhythmias, low cardiac output, and/or high inotropic support and
      optimized to achieve the highest systolic and mean arterial pressures. The
      following four pacing modes were used: (1) AV synchronous or AV sequential pacing
      with individually optimized AV delay in 11 patients with first- to third-degree
      AV block; (2) AV sequential pacing using transesophageal atrial pacing in
      combination with a temporary DDD pacemaker for atrial tracking and ventricular
      pacing in three patients with third-degree AV block and junctional ectopic
      tachycardia, respectively, who had poor signal and exit block on atrial
      epicardial pacing wires; (3) R wave synchronized atrial pacing in eight patients
      with junctional ectopic tachycardia and impaired antegrade AV conduction
      precluding the use of atrial overdrive pacing; (4) Atrio-biventricular sequential
      pacing in two patients. Pressures measured during optimized pacing were compared
      to baseline values at underlying rhythm (13 patients with first-degree AV block
      or junctional ectopic tachycardia) or during pacing modes commonly used in the
      given clinical situation: AAI pacing (1 patient with slow junctional rhythm and
      first-degree AV block during atrial pacing), VVI pacing (2 patients with third
      degree AV block and exit block and poor sensing on epicardial atrial pacing
      wires) and dual-chamber pacing with AV delays set to 100 ms (atrial tracking) or
      150 ms (AV sequential pacing) in 7 patients with second- to third-degree AV block
      and functional atrial pacing wires. Optimized pacing led to a significant
      increase in arterial systolic (mean) pressure from 71.5 +/- 12.5 (52.3 +/- 9.0)
      to 80.5 +/- 12.2 (59.7 +/- 9.1) mmHg (P < 0.001 for both) and a decrease in
      central venous (left atrial) pressure from 12.3 +/- 3.4 (10.5 +/- 3.2) to 11.0 +/
      3.0 (9.2 +/- 2.7) mmHg (P < 0.001 and < 0.005, respectively). In conclusion,
      several techniques of individually optimized temporary dual chamber pacing
      leading to optimal AV synchrony and/or synchronous ventricular contraction were
      successfully used to improve hemodynamics in patients with heart failure and
      selected dysrhythmias after congenital heart surgery.

PMID- 10962748
TI  - Successful laser-assisted percutaneous extraction of four pacemaker leads
      associated with large vegetations.
AB  - A man with four endocardial pacemaker leads and two vegetations (1.5 cm and 1 cm)
      underwent successful percutaneous laser-assisted lead extraction. Although this
      procedure was complicated by embolization to a left pulmonary arterial branch,
      the patient recovered without sequelae. This article reviews the literature on
      lead extraction associated with large vegetations.

PMID- 10962749
TI  - Efficacy of single lead VDD pacing in patients with impaired and normal left
      ventricular function.
AB  - Atrial synchronous ventricular pacing seems to be the best pacing mode for
      patients with advanced AV block and impaired LV function. The long-term follow-up
      of single lead VDD pacing was studied in 33 patients with impaired LV function
      and compared to 42 patients with normal LV function. All patients received the
      same VDD lead and VDDR pacemaker. The lead model with 13-cm AV spacing between
      the atrial and ventricular electrode was implanted in 89% of the patients. Follow
      ups were 1, 3, 6, and 12 months after implantation. The percentage of atrial
      sensing and the P wave amplitude were determined at each follow-up. Minimal P
      wave amplitude at implantation was 2.0 +/- 1.4 mV in patients with impaired and
      1.7 +/- 0.9 mV with normal LV function (not significant). At the 12-month follow
      up, 33 patients with normal and 23 patients with depressed LV function remained
      paced in the VDD mode. The remaining patients died in five (impaired LV function)
      and seven cases (normal LV function) or their pacemakers were programmed to the
      VVI/VVIR pacing mode in four (impaired LV function) and three cases (normal LV
      function). P wave amplitude did not differ in the two groups (e.g., at month 12:
      impaired: 1.17 +/- 0.42 mV; normal: 1.09 +/- 0.49 mV). The atrial sensitivity was
      programmed in most patients to sensitive settings with no differences between the
      two groups (e.g., at month 12: impaired: 0.13 +/- 0.06 mV; normal: 0.13 +/- 0.05
      mV). The diagnostic counters indicated nearly permanent atrial sensing (e.g., at
      month 12: impaired: 99.3 +/- 2.2%; normal: 99.0 +/- 1.0 mV). In conclusions,
      single lead VDD pacing restored AV synchronous ventricular pacing in patients
      with normal and with impaired LV function indicating that it could be an
      alternative to DDD pacemakers, but not to dual-chamber pacing.

PMID- 10962750
TI  - A prospective randomized-controlled trial of ventricular fibrillation detection
      time in a DDDR ventricular defibrillator. Ventak AV II DR Study Investigators.
AB  - Implantable cardioverter defibrillators (ICDs) with dual chamber and dual chamber
      rate responsive pacing may offer hemodynamic advantages for some ICD patients.
      Separate ICDs and DDDR pacemakers can result in device to device interactions,
      inappropriate shocks, and underdetection of ventricular fibrillation (VF). The
      objectives of this study were to compare the VF detection times between the
      Ventak AV II DR and the Ventak AV during high rate DDDR and DDD pacing and to
      test the safety of dynamic ventricular refractory period shortening. Patients
      receiving an ICD were randomized in a paired comparison to pacing at 150
      beats/min (DDD pacing) or 175 beats/min (DDDR pacing) during ICD threshold
      testing to create a "worst case scenario" for VF detection. The VF detection rate
      was set to 180 beats/min, and VF was induced during high rate pacing with
      alternating current. The device was then allowed to detect and treat VF. The
      induction was repeated for each patient at each programmed setting so that all
      patients were tested at both programmed settings. Paired analysis was performed.
      Patient characteristics were a mean age of 69 +/- 11 years, 78% were men,
      coronary artery disease was present in 85%, and a mean left ventricular ejection
      fraction of 0.34 +/- 0.11. Fifty-two episodes of VF were induced in 26 patients.
      Despite the high pacing rate, all VF episodes were appropriately detected. The
      mean VF detection time was 2.4 +/- 1.0 seconds during DDD pacing and 2.9 +/- 1.9
      seconds during DDDR pacing (P = NS). DDD and DDDR programming resulted in
      appropriate detection of all episodes of VF with similar detection times despite
      the "worst case scenario" tested. Delays in detection may be seen with long
      programmed ventricular refractory periods which shorten the VF sensing window and
      may be avoided with dynamic ventricular refractory period shortening.

PMID- 10962751
TI  - The strength-duration curve and its importance in pacing efficiency: a study of
      325 pacing leads in 229 patients.
AB  - Pacemaker battery life is dependent on programmable parameters, principally pulse
      amplitude and pulse duration. High factory default settings cause excessive
      current drain. The strength-duration curve relates pacing threshold to pulse
      duration. The most energy efficient pacing occurs at chronaxie, a value of pulse
      duration derived from the curve. Strength-duration curves were calculated for 325
      acutely implanted pacing leads. Chronaxie and rheobase were compared for atrial
      and ventricular leads. Chronaxie was compared with actual programmed pulse
      duration. There were 101 atrial and 224 ventricular leads, all passive fixation.
      The curve fit was good, (mean error +/- SD) 0.024 +/- 0.06 V for atrial curves
      and 0.008 +/- 0.034 V for ventricular curves. Mean (+/- SD) atrial and
      ventricular chronaxies were 0.24 +/- 0.07 ms and 0.25 +/- 0.07 ms, respectively.
      A "Z" value of 1.4 indicated that chronaxies might have been from the same
      population. Mean (+/- SD) atrial and ventricular rheobases were 0.51 +/- 0.2 V
      and 0.35 +/- 0.13 V, respectively. A "Z" value of 7.1 (P < 0.001) suggested
      atrial and ventricular rheobases were from differing populations. All patients
      had factory default pulse durations of 0.45 ms or 0.5 ms, exceeding acute
      chronaxie by a factor of two, thus, demonstrating suboptimal pacing. We conclude
      that understanding the strength-duration curve is critical. Sensible programming
      of other pacing functions optimizes longevity. Battery drain is reduced by
      programming pulse duration to chronaxie with a doubling of voltage threshold at
      this point to achieve a safety margin. Further study of chronaxie drift with time
      is required.

PMID- 10962752
TI  - Reduction in defibrillation threshold using an auxiliary shock delivered in the
      middle cardiac vein.
AB  - Defibrillation in the middle cardiac vein (MCV) has been shown to reduce
      ventricular defibrillation thresholds (DFTs). Low amplitude auxiliary shock (AS)
      from an electrode sutured to the left ventricle at thoracotomy have also been
      shown to reduce DFT if delivered immediately prior to a biphasic shock (between
      the ventricular RV and superior vena caval (SVC) electrodes). This study
      investigates the impact on DFT of an AS shock from a transvenously placed MCV
      lead system. A standard defibrillation electrode was positioned in the RV in
      eight anesthetized pigs (35-43 kg). A 50 x 1.8-mm electrode was inserted in the
      MCV through an 8 Fr angioplasty guide catheter. A 150-V (leading edge) monophasic
      AS was delivered (95 microF capacitor) from the MCV-->Can with three different
      pulse widths (3, 5, 7 ms). A primary biphasic shock (PS) (95 microF capacitor,
      phase 1: 44% tilt, 1.6-ms extension and phase 2: 2.5-ms fixed duration) was
      delivered from the RV-->Can +/- AS. The four configurations were randomized and
      DFTs (PS + AS) assessed using a modified binary search. Ventricular fibrillation
      (VF) was induced with 60 Hz AC followed 10 seconds later by the test shock. The
      DFTs were compared using repeated measures analysis of variance (ANOVA). All
      configurations incorporating AS produced significant (P < 0.05) reduction in the
      DFT compared to no AS (13.8 +/- 7.4 J). There was no difference in the efficacy
      of differing pulse widths (P > 0.05); 3 ms (11.0 +/- 5.4 J), 5 ms (11.5 +/- 6.0),
      and 7 ms (10.6 +/- 5.3 J). In conclusion, delivering an AS from a transvenous
      lead system deployed in the MCV reduces the DFT by 23% compared to a conventional
      RV-->Can shock alone.

PMID- 10962753
TI  - Percutaneous electrocatheter technique for on-line detection of healed transmural
      myocardial infarction.
AB  - Healed myocardial infarction has been recognized by its particular tissue
      electrical impedance spectrum measured with intramural needle electrodes in
      animal models. The aim of this study was to develop a percutaneous approach for
      in vivo recognition of areas of healed myocardial infarction by measuring
      myocardial electrical impedance with an intracavitary contact electrocatheter.
      Electrical impedance (resistance and phase angle) of normal myocardium and of a 2
      month-old anterior transmural infarction were measured in nine chloralose
      anesthetized pigs by applying alternating currents from 1 kHz to 1 MHZ between a
      bipolar intracavitary catheter and a reference electrode placed on the epicardium
      (group I, n = 4) or on the precordium (group II, n = 5). Resistance of the
      infarcted myocardium was lower than that of healthy tissue at all current
      frequencies (ANOVA, P < 0.001) (i.e., at 1 kHz: 15 +/- 4 omega vs 50 +/- 19 omega
      in group I, and 64 +/- 13 omega vs 76 +/- 13 omega in group II). Phase angle at
      316 kHz best differentiated transmural infarction from normal tissue (group I: 
      2.5 +/- 1.9 degrees vs -14.8 +/- 4.6 degrees, P < 0.001; group II: +0.7 +/- 1.0
      degrees vs -2.7 +/- 1.4 degrees, P < 0.001). This study shows that analysis of
      myocardial impedance spectrum using a percutaneous intracavitary contact catheter
      approach permits on-line recognition of areas of healed transmural myocardial
      infarction. This technique may be useful to optimize clinical application of
      energy sources (i.e., radiofrequency ablation, laser myocardial
      revascularization).

PMID- 10962755
TI  - Eccentricities of dual chamber implantable pacemakers.
AB  - The consequences of a short 160 ms postventricular atrial refractory period
      (PVARP) were studied in 27 patients with Medtronic Elite series of pacemakers
      (programmed to the unipolar mode) by using chest wall stimulation and
      myopotential interference. Because the ventricular refractory period is
      nonprogrammable at 230 ms, appropriately timed signals produced As-Vr
      combinations where As is an atrial sensed event and Vr is a ventricular event
      detected in the ventricular refractory period. The As-Vr combination inhibited
      the release of the atrial stimulus at the completion of the atrial escape
      interval in the DDI, DDIR, DDD, and DDDR modes. A paced ventricular beat (Vp) was
      documented to initiate automatic PVARP extension in circumstances where Vp was
      preceded by a Vr event and the pacemaker interpreted the Vr-Vp sequence as 2
      ventricular events without an intervening atrial event and Vp as a ventricular
      premature beat. Knowledge of these eccentricities should facilitate the
      interpretation of complex pacemakers responses to interference.

PMID- 10962754
TI  - An approach to salvage a "frozen" pacing lead.
AB  - We report our experience with the use of an orthopedic drill to remove "frozen"
      pacemaker leads from the connector block during pacemaker generator replacements.
      Three cases are reported in which the leads were salvaged successfully using this
      technique.

PMID- 10962756
TI  - Surgery for postinfarction ventricular tachycardia: is it obsolete?

PMID- 10962757
TI  - An unusual electrocardiographic pattern in a patient with Wolff-Parkinson-White
      syndrome.

PMID- 10962758
TI  - Prenatal diagnosis of QT prolongation by magnetocardiography.
AB  - Magnetocardiography constitutes a new tool for monitoring fetal cardiac activity.
      The fetal magnetocardiogram (FMCG) recorded noninvasively over the maternal
      abdomen is detectable with high temporal resolution and permits analysis of all
      parts of the PQRST waveform. In this way measurements of cardiac time intervals,
      including the QT interval, become possible. The following article constitutes the
      first report of antenatal detection of QT prolongation in two fetuses by FMCG.

PMID- 10962759
TI  - Reversible cardiomyopathy after radiofrequency ablation of lateral free-wall
      pathway-mediated incessant supraventricular tachycardia.
AB  - Incessant supraventricular tachycardia leading to reversible cardiomyopathy has
      been reported. Cardiomyopathy usually only develops after prolonged episodes of
      tachycardia at a significant heart rate. Left ventricular free-wall pathways
      rarely cause fast and incessant tachycardia. Therefore cardiomyopathy has not
      been reported with left ventricular free-wall pathway-mediated supraventricular
      tachycardia. We report on two cases of left ventricular free-wall-mediated
      supraventricular tachycardia leading to reversible cardiomyopathy after
      radiofrequency ablation. These cases illustrate the difficulty in diagnosing
      tachycardia-mediated cardiomyopathy, as the tachycardia may be clinically silent.
      In addition, they emphasize the importance of making this diagnosis, as the
      cardiomyopathy is reversible.

PMID- 10962760
TI  - Ablation of noninducible idiopathic left ventricular tachycardia using a
      noncontact map acquired from a premature complex with tachycardia morphology.
AB  - We describe use of a novel noncontact system to permit mapping in a noninducible
      patient from a single premature ventricular complex with tachycardia morphology,
      thus guiding successful ablation after two previously failed conventional
      efforts. The instantaneous global electroanatomic map demonstrated fascicular
      macroreentry. Subsequent to ablation at an inferolateral site, there has been no
      clinical recurrence despite difficult arrhythmia control preprocedure. This case
      demonstrated that noncontact mapping can be used to create a potential map to
      guide successful ablation from a single premature ventricular complex in a
      patient with idiopathic left ventricular tachycardia that became noninducible at
      electrophysiological study.

PMID- 10962761
TI  - Defibrillator implantation via the iliac vein.
AB  - We describe a 23-year-old patient with idiopathic dilated cardiomyopathy in whom
      an implantable cardioverter defibrillator was implanted via the right external
      iliac vein. Addition of a subcutaneous patch was required to obtain an adequate
      safety margin for defibrillation.

PMID- 10962762
TI  - Placement of a defibrillation lead in the left subclavian vein from the right
      cephalic vein.
AB  - This case report highlights the feasibility and stability of transvenous
      placement of a second defibrillation lead in the left subclavian vein from a
      right cephalic vein approach. This was undertaken in a right-sided implant of an
      active can cardioverter defibrillator to lower defibrillation thresholds that
      would have otherwise precluded implant.

PMID- 10962763
TI  - More widespread use of subpectoral pulse generator placement.

PMID- 10962764
TI  - Alcohol consumption and mortality. What do we know and where should we go?

PMID- 10962765
TI  - UK government announces first major relaxation in the alcohol licensing laws for
      nearly a century: drinking in the UK goes 24-7.

PMID- 10962766
TI  - Alcoholism treatment and medical care costs from Project MATCH.
AB  - AIMS: This paper examines the costs of medical care prior to and following
      initiation of alcoholism treatment as part of a study of patient matching to
      treatment modality. DESIGN: Longitudinal study with pre- and post-treatment
      initiation. MEASUREMENTS: The total medical care costs for inpatient and
      outpatient treatment for patients participating over a span of 3 years post
      treatment. SETTING: Three treatment sites at two of the nine Project MATCH
      locations (Milwaukee, WI and Providence, RI). PARTICIPANTS: Two hundred and
      seventy-nine patients. INTERVENTION: Patients were randomly assigned to one of
      three treatment modalities: a 12-session cognitive behavioral therapy (CBT), a
      four-session motivational enhancement therapy (MET) or a 12-session Twelve-Step
      facilitation (TSF) treatment over 12 weeks. FINDINGS: Total medical care costs
      declined from pre- to post-treatment overall and for each modality. Matching
      effects independent of clinical prognosis showed that MET has potential for
      medical-care cost-savings. However, patients with poor prognostic characteristics
      (alcohol dependence, psychiatric severity and/or social network support for
      drinking) have better cost-savings potential with CBT and/or TSF. CONCLUSIONS:
      Matching variables have significant importance in increasing the potential for
      medical-care cost-reductions following alcoholism treatment.

PMID- 10962767
TI  - Desire for alcohol and outcome expectancies as measures of alcohol cue-reactivity
      in social drinkers.
AB  - AIMS: To assess the responsiveness of questionnaire measures of desire to drink
      and alcohol outcome expectancies. DESIGN: A subjective alcohol cue-reactivity
      paradigm (alcohol cue: sight, smell, taste) was used with a 2 x 2 between-subject
      design (n = 88), drink type (soft/alcoholic) and order of assessment (desire
      expectancy/expectancy-desire). Covariance analysis controlled for quantity of
      recent alcohol consumption. SETTING: A quiet alcohol research suite.
      PARTICIPANTS: Eighty-eight male and female social drinking students, recruited
      for a 'taste preference' survey. MEASURES: Three composite measures using
      questionnaire totals and subscales: of desire (DAQ), positive expectancy (AEQ)
      and negative expectancy (NAEQ). Timeline Follow-back procedure for recent
      consumption. FINDINGS: Subjective cue-reactivity was found for the DAQ total
      score and the subscales 'strong intentions and desires' and 'negative
      reinforcement'. Expectancies did not demonstrate alcohol cue-reactivity.
      CONCLUSION: The DAQ and subscales are sensitive measures of alcohol cue
      reactivity in social drinkers. Potential uses of the subjective cue-reactivity
      procedure with multi-factorial representations of cue reaction are identified.

PMID- 10962768
TI  - Early results from a school alcohol harm minimization study: the School Health
      and Alcohol Harm Reduction Project.
AB  - AIMS: The School Health and Alcohol Harm Reduction Project aims to reduce alcohol
      related harm by enhancing students' abilities to identify and deal with high-risk
      drinking situations particularly likely to be encountered by young people.
      DESIGN: The SHAHRP study has adopted a quasi-experimental research design,
      incorporating intervention and control groups and measuring change over a 3-year
      period. SETTING: The study is set in metropolitan, government secondary schools
      (13-17-year-olds) in Perth, Western Australia. The 14 schools involved in the
      SHAHRP study represent approximately 23% of government secondary schools in the
      Perth metropolitan area. PARTICIPANTS: The sample was selected using cluster
      sampling, with stratification by socio-economic area, and involves over 2300
      intervention and control students from junior secondary schools. Seventy-three
      per cent (73.7%) of students completed surveys at both baseline and first follow
      up. INTERVENTION: The intervention incorporated evidence-based approaches to
      enhance potential for behaviour change in the target population. The intervention
      is a curriculum-based programmeme with an explicit harm minimization goal and
      will be conducted in two phases over a 2-year period. MEASURES AND FINDINGS: The
      early results of the study demonstrate initial knowledge and attitude change,
      predicted by the students' involvement in the intervention. A surprising impact
      of the first phase of SHAHRP was the significant difference in alcohol
      consumption and harms between control and intervention groups, with the SHAHRP
      group demonstrating a significantly lower increase in alcohol consumption than
      the control group. Students who were supervised drinkers at baseline and who
      received the SHAHRP intervention were overwhelmingly represented in the change
      results. CONCLUSIONS: Results from phase one of the SHAHRP study suggest that
      classroom-based alcohol education programmemes can reduce harm, particularly in
      students who are supervised drinkers prior to the intervention.

PMID- 10962769
TI  - Substance dependence, family history of alcohol dependence and neuropsychological
      functioning in adolescence.
AB  - AIMS: It was hypothesized that adolescent substance dependence moderates the
      relationship between family history of alcohol dependence and neuropsychological
      functioning. DESIGN: This study compared the neuropsychological functioning of
      non-abusing and alcohol and drug-dependent adolescents with and without a family
      history of alcohol dependence using hierarchical multiple regressions and general
      factorial analyses. SETTING: Substance-dependent adolescents were recruited and
      tested in inpatient alcohol and drug abuse treatment programs after 3 weeks of
      abstinence. A matched sample of non-abusing adolescents was recruited from the
      same San Diego-area communities. PARTICIPANTS: Substance-dependent adolescents (n
      = 101) met DSM-III-R criteria for dependence on alcohol and at least one other
      substance. Non-abusing adolescents (n = 50) had no substance use disorders.
      Groups were comparable on socio-economic status. Participants were 44% female,
      ages 13-18, and had no serious head injuries or neurological disorders.
      MEASUREMENTS: Information was gathered on demographics, family history, substance
      involvement, and conduct disorder behaviors and adolescents were administered
      neuropsychological tests covering language, visuospatial, verbal memory,
      attention and executive functioning domains. FINDINGS: The hypothesis was
      supported for language and attention tests. Substance involvement interacted with
      family history of alcohol dependence to predict language and attention
      functioning. Family history negative non-abusers performed better than the other
      adolescents. CONCLUSIONS: The pattern of results suggests that family history of
      alcohol dependence and adolescent substance use are separate risk factors for
      poorer neuropsychological performance in youth.

PMID- 10962770
TI  - One-year follow-up of opiate injectors treated with oral methadone in a GP
      centred programme.
AB  - AIMS: To examine changes in drug-related behaviour in opiate-dependent injectors
      treated with oral methadone, in a shared care scheme where consumption of the
      daily dose is usually supervised by a community pharmacist. DESIGN: One-year
      cohort study. SETTING: Recruitment from the main routes into methadone
      prescribing in Glasgow during 1996: General Practitioner Drug Misuse Clinic
      Scheme and the Drug Problem Service. PARTICIPANTS: Current opiate injectors
      entering methadone treatment. FINDINGS: Among the 204 injectors recruited, 148
      (73%) were re-interviewed at 6 months and 118 (58%) at both 6 and 12 months.
      Twenty-nine per cent of the cohort remained continuously on methadone for 12
      months. In that group, over the 12-month period, self-reported daily opiate
      injecting reduced from 78% to 2%; overdose in the previous 6 months from 24% to
      2%; mean daily drug spend from 50 Pounds to 4 Pounds; and mean monthly number of
      acquisitive crimes reduced from 13 to three. Assuming participants lost to follow
      up were unchanged, significant improvements in the total cohort were seen in
      daily opiate injecting (from 80% at recruitment to 43% at 12 months), overdose
      (from 27% to 15%), mean daily drug spend (from 63 Pounds to 38 Pounds) and mean
      monthly number of acquisitive crimes (from 18 to 11). Discontinuation of
      treatment was mainly due to imprisonment (39%) or sanctions by the prescriber
      (33%). CONCLUSION: Treatment of opiate-dependent drug injectors with methadone in
      a community-wide general practitioner-centred scheme, with supervised daily
      consumption, was associated with major beneficial change for a substantial
      proportion of patients.

PMID- 10962771
TI  - A comparison of four buprenorphine dosing regimens using open-dosing procedures:
      is twice-weekly dosing possible?
AB  - AIMS: To compare opioid withdrawal symptoms during 24-, 48-, 72- and 96-hour
      buprenorphine dosing regimens and to evaluate subjects' preferences for these
      different dosing schedules. SUBJECTS: Fourteen opioid-dependent subjects
      participated in this study. They received daily sublingual maintenance doses of 4
      mg/70 kg (n = 4) or 8 mg/70 kg (n = 10) of buprenorphine. INTERVENTION: In the
      first study subjects received, in a random order, four dosing regimens for five
      repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg),
      double the daily maintenance dose every 48 hours (8 or 16 mg/70 kg), triple the
      daily maintenance dose every 72 hours (12 or 24 mg/70 kg), and quadruple the
      daily maintenance dose every 96 hours (16 or 32 mg/70 kg). Measures of subjective
      and observer opioid withdrawal symptoms were assessed prior to receipt of each
      dose. In a second study, subjects chose between the different dosing regimens.
      FINDINGS: Some withdrawal ratings increased during the less frequent dosing
      schedules in the first study. In the second study, 46% of subjects preferred the
      quadruple-every-fourth-day dosing regimen over every other option, and only 14%
      preferred to be dosed daily. CONCLUSIONS: These results suggest that some opioid
      dependent outpatients are willing and able to endure the withdrawal symptoms
      associated with less than daily dosing, and a twice-weekly dosing regimen may be
      possible.

PMID- 10962772
TI  - Influence of monopoly privatization and market liberalization on smoking
      prevalence in Japan: trends of smoking prevalence in Japan in 1975-1995.
AB  - AIMS: In Japan, smoking prevalence in males has been among the highest among
      industrialized countries, while the prevalence in females has remained relatively
      low. There have been long-term declining trends since the early 1970s. In the mid
      1980s, the public tobacco monopoly was privatized and the tobacco market was
      liberalized in Japan. This study examines whether the trends in smoking
      prevalence changed at the time of these market changes. DESIGN AND MEASUREMENTS:
      Smoking prevalence data, tabulated by age group and sex, were plotted over the
      period 1975-95. Trends of smoking prevalence were then analyzed by using linear
      regressions, and their changes at the time of monopoly privatization and market
      liberalization were examined by Chow tests. FINDINGS: The trends in smoking
      prevalence changed at the time of the monopoly privatization and trade
      liberalization in both males and females, except for the males in their twenties
      and thirties. Rates of decline in smoking prevalence diminished in many age
      groups and prevalence for younger females started to increase. CONCLUSIONS:
      Market changes, that result from the privatization of a public tobacco monopoly
      and trade liberalization, may adversely affect smoking prevalence in many age
      groups and in both sexes, unless effective countermeasures are taken.

PMID- 10962773
TI  - Gambling problems in substance abusers are associated with increased sexual risk
      behaviors.
AB  - OBJECTIVES: This study evaluated the association between gambling problems and
      HIV risk behaviors in substance abusers. PARTICIPANTS AND SETTING: One hundred
      and thirty-four substance abusers were recruited from advertisements placed in
      newspapers and at social service agencies. INTERVENTION: Gambling problems were
      assessed using the South Oaks Gambling Screen (SOGS). The Addiction Severity
      Index evaluated drug and psychosocial problems, and the HIV Risk Behavior Scale
      assessed risk behaviors. FINDINGS: Based on SOGS scores, 24% (n = 31) of
      substance abusers evidenced probable pathological gambling. Problem gambling
      substance abusers were more likely to be male than non-problem gamblers, but no
      other differences in demographic characteristics or drug use variables were
      noted. Compared to non-problem gamblers, problem gamblers reported more sex
      partners and less frequent use of condoms with casual and paid sex partners.
      Stepwise logistic regression confirmed the association between severity of
      gambling problems and more risky sexual behaviors; higher SOGS scores predicted
      having more than 50 sex partners, exchanging sex for drugs/money, and engaging in
      anal intercourse (p < 0.05). Participants with gambling problems were also less
      knowledgeable about HIV transmission. CONCLUSIONS: These data suggest that
      gambling problems may be a risk factor for contracting HIV. Increased efforts are
      needed to screen for and treat gambling problems among substance abusers.

PMID- 10962774
TI  - Psychosis in a methadone-substituted patient during interferon-alpha treatment of
      hepatitis C.
AB  - Interferon-alpha (IFN-alpha) is the only effective treatment for chronic
      hepatitis B and C. Over 2/3 of methadone-substituted patients suffer from chronic
      hepatitis C but a history of psychiatric disorders or drug addiction is still
      seen as a contraindication for IFN-alpha because of a possible increased risk of
      severe psychiatric side effects such as depression, suicide attempts or psychotic
      episodes. We report on the case of a 33-year-old patient with chronic hepatitis C
      and a positive psychiatric history (drug abuse, borderline personality and four
      suicide attempts). After 4 months of therapy with IFN-alpha he developed a
      psychosis with persecution mania, complex thought disorder, disturbance of sexual
      identity, sleeplessness, anxiety, depression and increased irritability with
      suicidal thoughts. Symptoms did not disappear after discontinuation of interferon
      treatment. To our knowledge, there are no other reports of persistent psychosis
      with a possible association to interferon treatment. Development of psychosis and
      other psychiatric side-effects may be an indication of possible neuromodulatory
      effects of IFN-alpha with long-term treatment. On the other hand, the treatment
      for hepatitis C was successful. Ideas for safer treatment in methadone patients
      with psychiatric co-morbidity and chronic hepatitis C are needed.

PMID- 10962775
TI  - Women with alcohol-related problems in Nepal.

PMID- 10962776
TI  - Evaluating relationships between craving and drug use.

PMID- 10962777
TI  - Cravings and drug use.

PMID- 10962778
TI  - Re: Comments on "Reactivity to alcohol-related stimuli in the laboratory and in
      the field: predictors of craving in treated alcoholics: a reply"

PMID- 10962779
TI  - Out-of-hours care: ensuring accessible high quality care for all groups of
      patients.

PMID- 10962780
TI  - Why aromatherapy works (even if it doesn't) and why we need less research.

PMID- 10962781
TI  - Inequalities in access to coronary angiography and revascularisation: the
      association of deprivation and location of primary care services.
AB  - BACKGROUND: Coronary artery surgery reduces re-infarction rates and mortality in
      patients with ischaemic heart disease. This study examines inequality in relation
      to primary care services. AIM: To determine the effect of primary care services
      on access to coronary angiography and revascularisation. METHOD: A cross
      sectional survey of all 180 Nottinghamshire practices in the Trent region that
      were in existence between 1993 and 1997. The numbers of coronary bypass grafts,
      angioplasties, and angiographies were determined from the regional National
      Health Service database and linked to a database of general practice
      characteristics. Poisson regression analysis was used to determine the
      relationship between the angiography and revascularisation rates and the
      following practice characteristics: deprivation score, distance from nearest
      secondary or tertiary referral centre, medical cardiology admission rate for
      ischaemic heart disease, fundholding status, and partnership size. Multiple
      linear regression analysis was used to determine the relationship between
      practice characteristics and the waiting times for revascularisation and
      angiography. RESULTS: Practices with high deprivation scores had significantly
      lower rates of utilisation of angiography and revascularisation procedures. Their
      patients also waited longer for angiography. Practices that were 20 km or further
      from a revascularisation centre had significantly lower angiography and
      revascularisation rates. On average, their patients had to wait more than twice
      as long for an angiography compared with patients from nearer practices.
      Fundholding practices had higher angiography rates but similar revascularisation
      rates compared with non-fundholding practices. CONCLUSION: The results suggest
      that there may be some under-investigation and/or treatment of patients with
      ischaemic heart disease from 'deprived' practices and for those from practices
      far from a secondary or tertiary referral centre.

PMID- 10962782
TI  - Can general practitioners influence the nation's health through a population
      approach to provision of lifestyle advice?
AB  - BACKGROUND: Lifestyle advice from general practitioners (GPs) has been shown to
      have a positive effect on population health. In practice, GPs provide lifestyle
      advice to a minority of their patients only, those who are high risk or already
      have symptoms. AIM: To look in depth at GPs' attitudes towards adopting a
      population approach to lifestyle advice and to use these results to identify ways
      of maximising the potential of GPs to affect population health. METHOD: Thirty
      six GPs, purposively sampled by identifying characteristics likely to affect
      their health promotion activity, participated in a focus group study. Data from
      the focus groups were transcribed verbatim and analysed using standard methods.
      RESULTS: The main themes that emerged suggested that GPs do not take a population
      approach to lifestyle advice because they prefer a high risk approach and doubt
      their ability to be effective in a population approach. GPs believed that social,
      cultural, and environmental factors were the most important determinants of
      population health. Furthermore, they were concerned about the detrimental effects
      on the doctor-patient relationship of providing lifestyle advice to all patients.
      GPs believed that a multi-agency, centrally co-ordinated approach was the
      preferred way to improve population health and that their role should be limited
      to secondary prevention. CONCLUSION: Large amounts of resources would be
      necessary to convince GPs to adopt a population approach to lifestyle advice.
      Measures to tackle the social and environmental determinants of health may be a
      more effective and efficient means of improving the nation's health.

PMID- 10962783
TI  - Social variation in reasons for contacting general practice out-of-hours:
      implications for daytime service provision?
AB  - BACKGROUND: Contact with general practice out-of-hours services increases with
      socioeconomic deprivation. The reasons for this association are unclear but may
      include variations in access to daytime services or differences in morbidity.
      AIM: To identify the reasons for contact with the Glasgow Emergency Medical
      Service (GEMS) in relation to patient sociodemographic characteristics and the
      nature of the presenting problem. METHOD: All contacts with GEMS over a one-week
      period (n = 3193) in October 1996 were identified and a random 1:2 sample were
      sent a postal questionnaire investigating their reasons for contacting the
      service. Sociodemographic data and presenting problems were extracted from the
      service contact sheet. Data were analysed using correspondence analysis. RESULTS:
      Correspondence analysis identified two factors characterised as 'perceived
      problems with daytime services' and 'perceived urgency'. Scores on the former
      dimension were significantly associated with age (P < 0.0001), gender (P <
      0.0001), socioeconomic category (P < 0.0001), and presenting problem (P = 0.015)
      and scores were higher in adults, in males, among the non-affluent (particularly
      those resident in deprived areas), and in those presenting with a musculoskeletal
      problem. Scores on the latter dimension were significantly associated with age (P
      < 0.0001) and presenting problem (P < 0.0001). Scores tended to increase after
      childhood and for each of the five most frequent categories of presenting problem
      relative to other symptoms. CONCLUSIONS: Compared to those from affluent areas,
      patients from non-affluent areas appear to perceive difficulties accessing their
      general practitioner during surgery hours and may contact out-of-hours services
      as an alternative.

PMID- 10962784
TI  - A comparison of individual and population smoking data from a postal survey and
      general practice records.
AB  - BACKGROUND: Data on smoking held by general practitioners (GPs) may contribute to
      clinical care and to an assessment of population health. However, these data are
      prone to several biases and their validity has not been tested. AIM: To examine
      the accuracy of general practice data as an estimate for population prevalence of
      smoking and to estimate the accuracy of GP data on individuals' smoking habit
      compared with self-report. METHODS: A postal questionnaire on smoking habit over
      the past six years was sent to a random sample of individuals aged 15 to 74 years
      and registered with five out of seven general practices in one part of Leicester.
      GP records of those sampled were examined for an entry of smoking status over
      this period. RESULTS: Response rate to the postal questionnaire was 1906 out of
      2490 (76.5%). Reported smoking prevalence was 35.2%. Of those notes sampled, 1784
      out of 2432 (73.4%) had an entry about smoking recorded between 1991 and 1996.
      Patients recorded as smokers were less likely to respond to the postal
      questionnaire than non-smokers. Using practice data to ascribe smoking status to
      non-responders produced an estimated prevalence of 38.6%. Using questionnaire
      data alone as the 'gold standard', the last practice record collected since 1991
      overestimated current smoking prevalence by a factor of 1.22; using questionnaire
      data supplemented by practice data for non-responders as the 'gold standard'
      meant that the overestimate was by a factor of 1.11. Data from notes and the
      questionnaire were available for 1398 individuals and 2188 observations. Levels
      of agreement were high (kappa = 0.83). CONCLUSION: GP-held data are valid for
      individuals but over-estimate smoking prevalence at a population level.

PMID- 10962785
TI  - National evaluation of general practitioner commissioning pilots: lessons for
      primary care groups.
AB  - BACKGROUND: The national evaluation of general practitioner (GP) commissioning
      pilots was commissioned by the Department of Health in 1997 as part of its Policy
      Research Programme. It was conducted by the Health Services Management Centre at
      the University of Birmingham. AIM: To monitor the development of the 40 national
      pilot sites, identify the factors that inhibited or facilitated progress, and
      consider the implications for the implementation and development of primary care
      groups (PCGs). METHOD: Semi-structured face-to-face interviews with GPs, health
      authority (HA) managers, and pilot managers from each of the 40 pilot sites (141
      interviews in total) and focus group discussions with nurses, social services
      officers, and community health council officers in the 40 sites. RESULTS:
      Stakeholders reported the key achievements of the pilots during their first six
      months as being improved collaboration between GPs, the establishment of
      organisational arrangements, and work towards managing the group prescribing
      budget. Obstacles for the groups included changes to government policy regarding
      primary care, the workload involved for clinical staff, the pilots' relationship
      with the local HA, and problems with information management and technology
      (IM&T). A more detailed analysis of the pilots' management arrangements,
      prescribing work, IM&T support, and stakeholder involvement points to a set of
      lessons for emerging PCGs. CONCLUSIONS: In their early stages of development,
      PCGs are likely to focus on issues of structure and process. Prescribing will be
      an area receiving particular attention, prefiguring some of the challenges of
      clinical governance in primary care. IM&T will prove to be more problematic than
      first assumed. The involvement of a wider range of stakeholders will be addressed
      by primary care groups, particularly in relation to GPs and nurses.

PMID- 10962786
TI  - The impact of nursing home patients on general practitioners' workload.
AB  - BACKGROUND: Although the number of people in nursing homes has risen
      substantially in recent years, the shift of responsibility into general practice
      has rarely been accompanied by extra resources. These patients may be associated
      with a higher general practitioner (GP) workload than others of similar age and
      sex. AIM: To assess the GP workload associated with nursing home residents and
      its associated costs. METHOD: All nursing home residents aged over 65 years and
      registered with nine Nottinghamshire practices during one year were matched with
      patients living in the community for general practice, age, and sex. Data were
      collected retrospectively for both groups on key workload measures. Costs for the
      workload measures were calculated using published estimates. RESULTS: Data were
      collected for 270 pairs of patients. Nursing home patients had more face-to-face
      contacts in normal surgery hours, telephone calls, and out-of-hours visits. The
      mean workload cost per month of a nursing home patient (assuming that one patient
      was seen per visit) was estimated to be 18.21 Pounds (10.49 Pounds higher than
      the cost of controls). A sensitivity analysis demonstrated that potential savings
      in visiting costs associated with increasing the numbers of patients seen per
      visit were 27% for one extra patient seen per visit and 44% for four extra
      patients. CONCLUSION: Nursing home residents were associated with higher workload
      for GPs than other patients of the same age and sex living in the community. Our
      costings provide a basis for negotiating suitable reimbursement of GPs for their
      additional work.

PMID- 10962787
TI  - Providing palliative care in primary care: how satisfied are GPs and district
      nurses with current out-of-hours arrangements?
AB  - The complex needs of palliative care patients require an informed, expert, and
      swift response from out-of-hours general medical services, particularly if
      hospital admission is to be avoided. Few general practitioners (GPs) reported
      routinely handing over information on their palliative care patients,
      particularly to GP co-operatives. District nurses and inner-city GPs were least
      satisfied with aspects of out-of-hours care. Most responders wanted 24-hour
      availability of specialist palliative care. This indicates a need to develop and
      evaluate out-of-hours palliative care procedures and protocols, particularly for
      GP co-operatives, and to improve inter-agency collaboration.

PMID- 10962789
TI  - Lesbians and cervical screening.
AB  - Confusion exists in clinical practice about whether lesbians should be offered
      routine cervical smears. We found cervical smear abnormalities in a sample of 624
      lesbians, including those who had never been sexually active with men. These
      findings suggest that lesbians should be routinely offered cervical cytology as
      part of the national screening programme. Evidence of human papilloma virus (HPV)
      infection in the 'exclusively lesbian' group indicates that sexual transmission
      of HPV may occur between women. The belief by some lesbians that they have less
      need for cervical smears, coupled with poor uptake of cervical screening by a
      significant proportion, demonstrates a need for education of lesbians and health
      service providers.

PMID- 10962790
TI  - A study of junior doctors to investigate the factors that influence career
      decisions.
AB  - Both pre-registration house officers and general practitioner (GP) registrars
      agree on several desirable and undesirable factors that define their ideal
      career. These relate to fulfilling clinical work and preservation of a meaningful
      personal life. Many young doctors regret their choice of medicine as a career
      because of poor job conditions and stress and perceive career advice as
      inadequate. GP's influence over junior doctors at the time of their career
      decision making is very limited compared with that of consultants.

PMID- 10962788
TI  - When questionnaire response rates do matter: a survey of general practitioners
      and their views of NHS changes.
AB  - This paper investigates whether general practitioners (GPs) who do not
      participate in questionnaire surveys (non-responders) hold different views on
      participation in primary care reorganisation than their more compliant
      colleagues. A survey of 72 GPs' involvement in a pilot primary care prescribing
      group elicited an initial response of 74%. Non-responders were then approached
      personally and persuaded to complete the questionnaire. Comparison of the
      responders and the non-responders showed that the latter did differ significantly
      from the responders in many of their views. This difference needs to be
      considered whenever the results of surveys are used to guide policy-making in the
      more corporate model of primary care that is now emerging.

PMID- 10962791
TI  - The use of alternative medicines by somatoform disorder patients in Spain.
AB  - Somatisation disorder patients show a high rate of alternative medicine
      consultations but most of them do not disclose this fact to the doctor owing to
      fear of reprisals. The reasons given for using these medicines do not equate to
      sociodemographic characteristics, psychiatric diagnosis or personality traits but
      instead to dissatisfaction with medical care and with diagnosis. These patients
      appreciate the longer and more frequent consultations as well as the better
      doctor-patient relationship of alternative medicines.

PMID- 10962792
TI  - Combating information overload: a six-month pilot evaluation of a knowledge
      management system in general practice.
AB  - A six-month prospective study was conducted on the usefulness and usability of a
      representative electronic knowledge management tool, the WAX Active Library, for
      19 general practitioners (GPs) evaluated using questionnaires and audit trail
      data. The number of pages accessed was highest in the final two months, when over
      half of the access trails were completed within 40 seconds. Most GPs rated the
      system as easy to learn, fast to use, and preferable to paper for providing
      information during consultations. Such tools could provide a medium for the
      activities of knowledge officers, help demand management, and promote sharing of
      information within primary care groups and across NHSnet or the Internet.

PMID- 10962793
TI  - Does psychological status predict the presentation in primary care of women with
      a menstrual disturbance?
AB  - Thirty per cent of women aged 35 years and over suffer from heavy menstruation,
      but only 7% have consulted a doctor in the previous six months, suggesting that a
      significant number of these women do not consult a general practitioner. There is
      evidence that women who report heavy menstruation are more likely to have
      symptoms of psychological disturbance. This study sets out to determine whether
      the presence of symptoms of anxiety and depression might be linked to subsequent
      consultation for increased vaginal bleeding in primary care.

PMID- 10962794
TI  - Aromatherapy: a systematic review.
AB  - Aromatherapy is becoming increasingly popular; however there are few clear
      indications for its use. To systematically review the literature on aromatherapy
      in order to discover whether any clinical indication may be recommended for its
      use, computerised literature searches were performed to retrieve all randomised
      controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE,
      British Nursing Index, CISCOM, and AMED. The methodological quality of the trials
      was assessed using the Jadad score. All trials were evaluated independently by
      both authors and data were extracted in a pre-defined, standardised fashion.
      Twelve trials were located: six of them had no independent replication; six
      related to the relaxing effects of aromatherapy combined with massage. These
      studies suggest that aromatherapy massage has a mild, transient anxiolytic
      effect. Based on a critical assessment of the six studies relating to relaxation,
      the effects of aromatherapy are probably not strong enough for it to be
      considered for the treatment of anxiety. The hypothesis that it is effective for
      any other indication is not supported by the findings of rigorous clinical
      trials.

PMID- 10962795
TI  - Welfare to work: the role of general practice.
AB  - This paper considers the potential effects of the government's Welfare to Work
      policy on general practitioner (GP) working patterns, and aims to explore the
      relationship between unemployment, ill health, and GP sickness certification.
      Social security and employment policy initiatives are discussed in relation to
      the literature on the relationship between unemployment and ill health,
      sociological and psychological perspectives on work and unemployment,
      medicalisation of unemployment, adjudication of fitness for work, re-employment
      and health, and treatment of barriers to employment. The authors postulate that
      Welfare to Work policy may depend for its success on the crucial role of general
      practice in sickness certification.

PMID- 10962796
TI  - Competency model for general practice.

PMID- 10962797
TI  - Chlamydia screening in primary care.

PMID- 10962798
TI  - Chlamydia screening in primary care.

PMID- 10962799
TI  - E-mail consultations.

PMID- 10962800
TI  - Overcoming the constraints to becoming paperless.

PMID- 10962802
TI  - Primary care groups and research.

PMID- 10962801
TI  - Prescribing costs.

PMID- 10962803
TI  - [Neurological complications of renal transplant].
AB  - Advances in surgical procedures and new immunosuppressor therapies have improved
      the outcome of renal grafts. However, these changes have been accompanied by
      infectious, neoplastic and neurologic complications. The purpose of this study
      was to determine the incidence of neurologic complications among 542 patients
      receiving a renal transplant (from living or cadaveric donors) at CEMIC between
      1970 and 1996. Neurologic complications occurred in 43 patients (8%) as follows:
      8 meningitis (1.5%), 8 acute confusional syndrome (1.5%), 7 encephalitis (1.3%),
      7 cerebrovascular accidents (1.3%), 6 convulsions (1.1%), 3 tumors (0.5%), 3
      femoral nerve lesion (0.5%), and 1 epidural lipomatosis (0.1%). Etiologic agents
      most commonly observed in meningitis were: Cryptococcus neoformans, Listeria
      monocytogenes and Mycobacterium tuberculosis. Major difficulties arose in the
      diagnosis of encephalitis. Diagnosis of the above complications required clinical
      astuteness and repeated bacteriologic, serologic and imaging studies.

PMID- 10962804
TI  - [Mesial temporal sclerosis syndrome in adult patients].
AB  - Magnetic resonance imaging (MRI) has become an essential tool in the work-up of
      epilepsy. Since its appearance it has been possible to identify pathologies, such
      as hippocampal sclerosis (HS), that had previously only been detected by
      histopathological assays. The aim of this study was to analyze the clinical
      manifestations, EEG and the outcome of patients with HS as shown by MRI. We
      revised the clinical histories of 384 outpatients from the Epilepsy Center, Ramos
      Mejia Hospital, who had been studied by MRI. Thirty five of them (15.5%) had a
      diagnosis of HS, based on the structural changes observed on the images. Six
      patients were excluded because of incomplete clinical data. Therefore, we studied
      29 patients including 15 men. The mean age was 32.7 +/- 10.2 years (range: 19
      58). All of them had partial seizures. Ten subjects had had febrile convulsions
      (34.5%) in childhood. Neurological examination was normal in all subjects.
      Interictal EEG showed focal abnormalities that were coincident in their location
      with the MRI abnormalities in 16 patients (55.1%). Fourteen patients (48.3%)
      showed right side hippocampal lesions on MRI, thirteen on the left side (44.9%)
      and 2 bilateral HS (6.8%). Twenty-seven patients (93.1%) had intractable
      epilepsy. Anterior temporal lobectomy was performed in 3 subjects with good
      outcome. The identification of these patients who present certain clinical and
      MRI characteristics, provides an opportunity to define the mesial temporal
      sclerosis syndrome. This could benefit patients in their prognosis and for
      specific treatments.

PMID- 10962805
TI  - [Diagnosis of tuberculosis in children in provinces of Argentina].
AB  - Confirming the diagnosis of pediatric tuberculosis is cumbersome, due to the
      clinical features (generally paucibacillary forms) of the disease. This national
      study was undertaken in order to establish: the features of childhood
      tuberculosis at the time of diagnosis, the criteria on which the pediatricians
      based the diagnosis, the bacteriologic contribution to the diagnosis and the
      quality of notifications to the National Programme. Medical and laboratory
      records were reviewed for children under 15 years of age who were diagnosed with
      tuberculosis disease or primary infection during 1995. The study included
      children cared for at health centres from Argentinean provinces (capital city
      excluded) where pediatricians accepted to participate. Four hundred cases (17% of
      childhood notifications to the National Programme) and 81 primary infections were
      studied. The percentage of children studied by means of chest radiology, presence
      of symptoms, Mantoux test, case contact investigation and bacteriology were
      95.3%, 79.6%, 90.1%, 92.7% and 35% for pulmonary cases, respectively, and 87.7%,
      100%, 87.7%, 85.9% and 78.9% for extra-pulmonary cases, respectively. Of the
      evaluated pulmonary cases, 99.1% had abnormal x-rays, 79.0% had a tuberculin test
      > or = 10 mm, 79.8% had symptoms and 80.2% had a history of close contact. All
      extra-pulmonary patients had symptoms at the time of diagnosis; 63.0% had
      abnormal chest radiograph at diagnosis. Bacteriologic confirmation was achieved
      in 10.7% of the cases (20.8% and 40.0% of the investigated pulmonary and extra
      pulmonary cases, respectively). This study would indicate that the diagnosis is
      made at relatively early stages of the disease. In general, recommendations of
      the Argentine Society of Pediatrics were followed. A low rate of bacteriological
      proof of diagnosis was observed, probably due to the scarce bacteriologic
      investigation and the low yield achieved in culturing pulmonary specimens. The
      study found under-register of cases and lack of precision in the information
      reaching the National Programme.

PMID- 10962806
TI  - [Allogeneic hematopoietic transplantation with stem cells extracted from
      peripheral blood].
AB  - Fifty three patients (pts) received an allogeneic hematopoietic transplant using
      peripheral blood progenitor cells (PBPC). Diagnosis were acute myeloid leukemia
      (AML) in 16 pts, acute lymphoblastic leukemia (ALL) in 15, chronic myeloid
      leukemia (CML) in first chronic phase in 12, aplastic anemia in 4, myelodysplasia
      in 3 and Hodgkin's disease, major thalasemia and Hunter's syndrome in one each.
      Mean age was 20 years-old (2-55), 28 males and 25 females. Conditioning regimens
      were total body irradiation with 1200 cGy and cyclophosphamide 120 mg/kg in 38
      pts, busulfan 16 mg/kg and cyclophosphamide 120 mg/kg in 10 pts, total lymphoid
      irradiation and cyclophosphamide in 3, 2 pts received other chemotherapy based
      conditionings. PBPC were infused unmanipulated through a central catheter. Graft
      versus host disease (GVHD) prophylaxis was cyclosporin and short course
      methotrexate. Donors were 6/6 HLA compatible siblings in 52 cases and 5/6 match
      in one case. PBPC mobilization was done with G-CSF at a dose of 10
      micrograms/kg/day subcutaneously for four days, pheresis started on day 5. Bone
      marrow harvest was also done in the first thirty cases. Mean cellularities for
      CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg) were 4.12; 4.59; 2.57; 1.9; 0.55
      and 0.68, respectively. Mean recovery of neutrophils > 500/microL was obtained on
      day +11 and platelets > 20,000/microL on day +13. Patients were hospitalized for
      a mean period of 26 days (range 18-39) and days with parenteral antibiotics were
      12.2 (5-45). Two pts had venoocclusive disease of the liver. Transplant related
      mortality was 15%. Acute graft versus host disease (GVHD) was observed in 43.4%
      of pts, only 5 pts had acute GVHD III or IV. Mean time for aGVHD diagnosis was
      +23 (8-76). Forty three pts were evaluable for chronic GVHD with a mean follow-up
      of 18 months (4-39). Chronic GVHD was observed in 26.4% by day +240, only 2 pts
      developed severe cGVHD. The present experience demonstrates an acceptable
      incidence for cGVHD; however, taking into account recent reports showing an
      increase of this complication, it seems reasonable not to perform this procedure
      for non-malignant diseases in which graft versus malignancy effect is not to be
      expected.

PMID- 10962807
TI  - [Diagnosis by directed mutagenesis of a mutation at the hMSH2 gene associated
      with hereditary nonpolyposis colorectal cancer].
AB  - Hereditary nonpolyposis colorectal cancer (NHPCC) is the most common form of
      inherited colon cancer and one of the most frequent autosomal dominant disorders.
      HNPCC presents an early onset of colorectal cancer (< 50 years), proximal
      localization of the colonic tumors, and high risk of developing multiple primary
      colorectal tumors as well as extracolonic tumors. This disease is caused by
      mutations in at least four DNA mismatch repair genes, (hMSH2, hMLH1, hPMS1 and
      hPMS2) and estimations indicate that it affects 1:200-1:2,000 people in the
      Western populations. The identification of the genes responsible for HNPCC has
      prompted the search for mutations in affected individuals. DNA from an affected
      member of a family was sent to a Dutch HNPCC Diagnosis Centre. This Centre
      reported a germinal mutation, which introduces a premature stopcodon and causes
      the production of a truncated protein. This particular mutation has not been
      previously registered in the database of mutations related to this disease. After
      the identification of the mutation in the index patient, we have developed a
      quick and efficient procedure for detecting mutations in the rest of the family.
      The methodology is based on the amplification of the exon 13 in the hMSH2 gene
      using a forward primer that abuts the mutation site and introduces the cutting
      sequence of the enzyme Haelll++ only in the wild type allele. At present,
      seventeen members of the family have been diagnosed and nine have been found to
      be affected. The methodology is simple, specific, sensitive, inexpensive and
      applicable in low complexity laboratories.

PMID- 10962808
TI  - Urinary heparan sulphate is increased in normoalbuminuric diabetic patients.
AB  - Forty-nine normoalbuminuric diabetic patients were studied: 22 males and 27
      females, in whom urinary heparan sulphate (HS), albuminuria, creatininemia,
      creatininuria, creatinine clearance, HbA1c and arterial pressure (AP) were
      determined. Two groups were discerned: group 1, Type 1 DM, diabetic cases (n =
      16); and group 2, Type 2 DM diabetic cases (n = 33). Patients were compared with
      24 healthy controls: 12 men and 12 women, who showed a mean value +/- SD of 0.36
      +/- 0.18 mg/24 h HS with significant differences between males and females (0.43
      +/- 0.15 versus 0.28 +/- 0.17, respectively; p = 0.02). The total population of
      diabetic cases rendered a mean of 0.68 +/- 0.44 and comparison with controls
      proved highly significant (p < 0.001). Globally, male patients had a mean of 0.82
      +/- 0.48 and females 0.54 +/- 0.35, with p < 0.02. Group 1 and 2 values of HS
      were not significantly different. HS levels failed to correlate either with age,
      body mass index (BMI), time since onset of diabetes, albuminuria, creatininemia,
      creatininuria, creatinine clearance, HbA1c or arterial hypertension. To conclude:
      both normal and diabetic males eliminate a greater quantity of HS than females.
      Normoalbuminuric diabetic patients of both types eliminate a greater quantity of
      HS regardless of arterial pressure and time since onset of diabetes.

PMID- 10962809
TI  - Interleukin 2 induction of proliferation in resting T lymphocytes requires
      contact with monocytes.
AB  - Resting human T cells are known to express significant numbers of intermediate
      but none or barely detectable low and high affinity IL-2 receptors (IL-2R). IL-2
      alone failed to induce proliferation in these cells. However, in presence of
      small proportion of autologous monocytes, as low as 22 pM, IL-2 induced high
      levels of proliferation in resting T cells. Introduction of a semi permeable
      membrane between the two cell types or addition of an anti-CD11b mAb inhibited
      such induction of proliferation by IL-2. Neither recombinant IL-1 nor IL-1
      containing cell-free extracts from activated monocytes substituted for intact
      monocytes. Autologous B cells failed to replace monocytes. Using antigen-specific
      cloned human T cells we have shown a lack of requirement for antigen. The
      proliferation was inhibited by anti-IL-2R alpha mAb. IL-2 appears to be unique
      since neither IL-4 nor IL-6, alone or in presence of monocytes, led to induction
      of proliferation in resting T cells. Combination of IL-2 and monocytes induced
      proliferation in all T cell subpopulations (CD4+, CD8+, CD45RA+ and CD45RO+) and
      antigen-specific clones examined. It also induces mRNA and surface expression of
      IL-2R alpha, appearance of high affinity IL-2R and induction of proliferation in
      large proportions of T cells. As in humans, the IL-2 induction of proliferation
      in murine resting T cells required contact with syngeneic monocytes, suggesting
      that such a mechanism of T cells activation is highly conserved.

PMID- 10962810
TI  - [Glomerular filtration rate with Tc99m DTPA. Comparison of methods].
AB  - Glomerular filtration rate (GFR) is an important index of renal function. The aim
      of this study was to compare the GFR with 99m Tc. DTPA without urine collection
      estimated with three, two and single-sample methods. We studied 148 patients (54
      women and 94 men, 3-84 years old) with diverse renal diseases. After intravenous
      administration of Tc99m DTPA three (90-120-180 min. Method 1; n = 44) or two (120
      and 180 min or 180 and 240 min Method 2, n = 104) blood samples were taken. The
      GFR (ml/min) were calculated using monoexponential analysis, or with only the
      sample of the 180 or 240 min with the methods of Jacobsson, Russel, Groth-Aasted,
      Dakubu and Constable. RESULTS: 1) In 37/148 (25%) the GFR by Method 1-2 was less
      than 30 ml/min. All the single-sample methods did not perform well. 2) in 107/148
      (75%) the GFR using method 1 and 2 was superior to 30 ml/min. The single sample
      methods showed clinically acceptable absolute error differences with method 1 and
      2. However, we cannot suggest a preferable one single sample method that covers
      all the range of GFR that we analyzed. In conclusion, the 2 sample technique
      provides an estimate of GFR and we also suggest ultrafiltering the plasma before
      measuring radioactivity to give better accuracy in calculating GFR.

PMID- 10962811
TI  - [Zoonotic parasitosis transmitted by dogs in the Chaco Salteno, Argentina].
AB  - Toxocara canis and Ancylostoma spp. are geohelmints that parasites dogs and can
      eventually affect humans, mainly children, causing visceral and cutaneous larva
      migrans respectively, constituting a serious public health problem. This study
      was carried out in two towns located in the xerophilous forest Chaco salteno
      where humans live closely with many animals, including dogs. Hematological values
      and anti-Toxocara canis antibodies, determined by ELISA in serum, were evaluated
      in 98 children from this area. Thirty-six children presented with eosinophilia of
      10% or higher in peripheral blood. Twenty out of 98 (20.4%) children had
      antibodies against antigen from L2 larvae of Toxocara canis. A high percentage
      (55.6%) of the children with eosinophilia presented anti-Toxocara canis
      antibodies. Nine children had multiple serpiginous lesions typical of cutaneous
      larva migrans. Feces from dogs were collected in the area where children lived,
      in order to search for parasite contamination. Three different techniques of
      stool examination were employed and eggs were counted. Out of the 106 feces
      examined, parasites were found in 82 samples (77.4%). Ancylostoma spp eggs were
      found in 74 (69.8%) samples and eggs from Toxocara canis were found in 19
      (17.2%). The average number of T. canis and Ancylostoma spp eggs/gr of feces,
      were 200 and 3,871 respectively. Giardia spp (14.5%), Trichuris vulpis (7.6%),
      Genus Endamoeba (2.8%) and Taenia spp (1.9%) were also identified in the stools.
      Sanitary control and health education in order to control these parasitoses are
      emphasized.

PMID- 10962813
TI  - [Effect of carrageenan and indomethacin on the growth of a murine fibrosarcoma].
AB  - In order to grow, solid tumors need to develop new blood vessels. Neoplastic
      cells secrete growth factors that stimulate angiogenesis and tumor growth. Since
      Carrageenan acts as in vitro blocking agent which interferes with growth factor
      receptor binding, we tested its action in vivo in order to analyze its growth
      inhibition capability in an experimental murine fibrosarcoma model. Indomethacin
      was used as a non-steroidal anti-inflammatory agent to neutralize the
      inflammatory action of Carrageenan. A murine fibrosarcoma was induced with
      methylcholanthrene in Balb/c mice and maintained by serial passage of tumor cells
      in mice of the same strain. Tumor volume was evaluated measuring two dimensions
      and applying the formula V = 0.4 x d2 x D. The mice with tumors were separated
      into groups; one of them was used as control and the other ones were treated with
      Indomethacin, Carrageenan and Carrageenan-Indomethacin. Tumor volume was compared
      between groups using the Student t Test. We demonstrated that Carrageenan and
      Indomethacin inhibit tumor growth. The inhibitory action of Carrageenan is
      significantly higher than the antitumoral effect of either Indomethacin or
      Carrageenan-Indomethacin.

PMID- 10962812
TI  - [Celecoxib vs indomethacin and acute gastric lesions in rats].
AB  - In 5 random groups of Wistar rats (n = 15 for each group), ulcerogenic doses of
      NSAIDs COX-1-COX-2 inhibitors such as indomethacin were compared with Celecoxib
      (COX-2 inhibitor); the production of antrum gastric ulcers and bowel and colon
      necrotic areas was studied. Celecoxib was given each 12 hs orally and
      subcutaneously during 5 days and gastrointestinal lesions were not found; in
      contrast, Celecoxib given after indomethacin aggravated antrum gastric ulcers (p
      < 0.001); intestinal massive necrosis and death were observed in all the rats. We
      conclude that Celecoxib does not induce gastrointestinal lesions in healthy
      mucosa; in contrast, Celecoxib amplifies the gastrointestinal lesions induced by
      indomethacin.

PMID- 10962814
TI  - [Effect prolonged GABAergic activation on the pubertal development of female
      rats].
AB  - We evaluated, in immature female rats, the effect of the GABAergic system on the
      reproductive axis and on pubertal development. Initially, using a prolonged
      treatment with aminooxyacetic acid (AOAA), increasing hypothalamic GABA (p <
      0.002), and decreasing GnRH and glutamate content (p < 0.05 and < 0.02). Treated
      rats showed diminished serum LH (p < 0.05) and estradiol (p < 0.005) levels.
      Vaginal opening occurred at 30.8 +/- 0.6 days in controls, and at 36.7 +/- 0.98
      days in AOAA-treated rats. Acute treatment with AOAA resulted in a decreased GnRH
      and glutamate output, and in an increased taurine release from superfused
      hypothalamic fragments. This effect was mimicked by the GABA-A and GABA-B
      agonists. The activation of the GABAergic system during postnatal days 23-29
      significantly restrains the hypothalamo-pituitary-ovaric axis and delays the
      onset of puberty. The existence of a physiological cross-talk between excitatory
      and inhibitory amino acid neurotransmitters regulating GnRH release during the
      onset of puberty is postulated.

PMID- 10962816
TI  - [Cystic adrenal lesion. Incidental finding].
AB  - We report a case of a non functioning cystic adrenal mass. It was incidentally
      found in an abdominal ultrasound carried out for unrelated symptoms. According to
      the classification of adrenal cysts it is a multilocular pseudocyst with wall
      fibrosis and calcification. The pseudocyst lining expresses Factor VIII
      suggesting a vascular origin.

PMID- 10962815
TI  - Acylglycerol synthesis in liver of type II diabetic rats fed a diet supplemented
      with either n-6 or n-3 fatty acids.
AB  - Liver is one of the tissues most actively involved in triacylglycerol synthesis
      and secretion. Hypertriglyceridemia is commonly associated with the diabetic
      state which has been detected in very young rats after the induction of
      experimental diabetes. In the present work, acylglycerol synthesis in liver of
      streptozotocin-treated rats, fed a diet supplemented with n-3 and n-6 fatty
      acids, was studied. At the onset of the experiment, plasma triacylglycerol levels
      increased significantly in diabetic animals when compared to controls. Two weeks
      after the dietary treatment, the aforementioned parameter decreased in diabetic
      animals consuming either n-6 or n-3 fatty acids. In control rats, n-3 fatty acids
      depressed triacylglycerol synthesis in liver microsomes. In the diabetic group
      both diets increased diacylglycerol and triacylglycerol synthesis. The addition
      of liver cytosolic fraction from control rats to the incubation medium,
      stimulated the triacylglycerol synthesis in all the groups. Nevertheless, the
      radioactivity recovered in the neutral lipid fractions was lower in the samples
      from rats fed n-3 fatty acids compared to n-6. We conclude that dietary n-3 fatty
      acids decreased significantly triacylglycerol plasma levels in diabetic rats
      probably through the inhibition of liver triacylglycerol secretion. In addition,
      there probably is an n-3 fatty acid sensitive factor in the liver cytosolic
      fraction able to depress triglyceride synthesis.

PMID- 10962817
TI  - [Sertraline. Adverse effects due to the superposition of serotonic and malignant
      neuroleptic syndromes].
AB  - A 57 year-old man chronically treated with 50 mg daily of sertraline was admitted
      to the emergency room with mental status changes, rigidity, seizure activity and
      autonomic instability. He was rapidly transferred to the Intensive Care Unit.
      Laboratory determinations revealed increases in serum enzymes, prevailing
      creatine phosphokinase with a peak level by the third day of 35,000 Ui/L. Initial
      low serum sodium (10 mEq/L) was attributed to inadequate antidiuretic hormone
      secretion. Supportive care included discontinuation of sertraline and lorazepam
      administration. Mental status, and rigidity returned to baseline within 60 hours.
      Differential diagnosis between the neuroleptic malignant syndrome and the
      serotonin syndrome could not be determined accurately because of the striking
      overlap of signs and symptoms of both syndromes.

PMID- 10962818
TI  - [Fisher's one and half syndrome with facial palsy as clinical presentation of
      giant cell temporal arteritis].
AB  - An ischemic stroke in an old patient is commonly due to thrombosis or embolism. A
      restriction in the differential diagnosis and not considering another etiology
      could occasion the loss of effective therapy and prevent major complications. We
      report the case of a patient who suffering from systemic symptoms for a few
      months, was admitted to the hospital with the one and a half syndrome described
      by Fisher, together with right facial palsy, both products of an ischemic pontine
      lesion. Bilateral biopsies of the temporal arteries were diagnostic of temporal
      arteritis and MRN of the cranium confirmed multiple ischemic lesions involving
      the pons. In conclusion, the diverse clinical presentations of temporal arteritis
      oblige us to consider it among the etiological options in older patients with
      neurological signs affecting the vertebral-basilar system, accompanied by
      systemic signs and symptoms and a high VSG. To avoid anterior ischemic optic
      neuropathy and other complications a quick diagnosis and treatment are necessary.

PMID- 10962820
TI  - [Images in medicine. Playboy's logo].

PMID- 10962819
TI  - Intestinal bleeding and occlusion associated with Shiga toxin-producing
      Escherichia coli O127:H21.
AB  - We report a case of a nine-year old boy with vomiting, abdominal pain and fever,
      who underwent surgery with a diagnosis of appendicitis in Mendoza and from whom a
      Shiga toxin-producing Escherichia coli (STEC) O127:H21 strain was recovered.
      Forty-eight hours after surgery he presented bilious vomiting and two episodes of
      intestinal bleeding. Laboratory findings included: hematocrit, 35%; blood urea
      nitrogen, 0.22 g/L. The urinary output was normal. The following day physical
      examination showed an alert mildly hydrated child, without fever but with
      distended and painful abdomen. The patient was again submitted to surgery with a
      diagnosis of intestinal occlusion. Bleeding and multiple adhesions in jejunum and
      ileum were found. The patient still had tense and painful abdomen and presented
      two bowel movements with blood; hematocrit fell to 29% and blood urea nitrogen
      rose to 0.32 g/L. STEC O127:H21 eae(-)/Stx2/Stx2vh-b(+)/E-Hly(+) was isolated
      from a stool sample. He was discharged after 10 days of hospitalization and no
      long-term complications such as HUS or TTP were observed. This is the first
      report, to our knowledge, on the isolation of E. coli O127:H21, carrying the
      virulence factors that characterize STEC strains, associated to an
      enterohemorrhagic colitis case. This serotype was previously characterized as a
      non-classic enteropathogenic E. coli (EPEC). STEC infections can mimic infectious
      or noninfectious pathologies. Therefore an important aspect of clinical
      management is making the diagnosis using different criteria thereby avoiding
      misdiagnoses which have occasionally led to invasive diagnostic and therapeutic
      procedures or the inappropriate use of antibiotics.

PMID- 10962821
TI  - [Images in medicine. Tuberous sclerosis with ocular manifestations].

PMID- 10962822
TI  - [Ethical principles of research in human beings and in animals].
AB  - All research on specific clinical aspects of human health and of patient
      investigating-community-ecosystem must be based philosophically on ethical
      principles which are not rigid rules but reference guides to humanize all
      research processes. We analyze the following principles: integrity/totality;
      respect for the individual which includes the ethical duties of no wrongdoing and
      autonomy; welfare, equity/justice. And for research in animals we include the
      principle of respect for the ecosystem. The international statements of the AMM
      and of the CIOMS are formulations containing protective ethical principles of
      human rights and humanitarian practices in animal research and they are of
      essential importance in any research.

PMID- 10962823
TI  - [Donor lymphocyte infusions as adoptive immunotherapy in patients with relapsed
      hematologic neoplasms post-allogenic transplant of hematopoietic progenitor
      cells].
AB  - An increasing body of literature has documented the usefulness of donor
      lymphocyte infusions in inducing remissions in patients relapsing post allogeneic
      hematopoietic progenitor cell transplantation. Efficacy was shown to depend on
      the disease entity; the best results have been reported in chronic myeloid
      leukemia in chronic phase, where the remission rate varied between 60 and 80%. In
      acute myeloid leukemia and myelodysplastic syndromes the remission rate ranged
      between 20 and 40% and in multiple myeloma the response rate was approximately
      40%. In contrast, results have been poor in acute lymphoid leukemia with only 10
      20% and even lower reported responses. Considering the efficacy of donor
      lymphocyte infusions in inducing responses in several hematologic neoplasias post
      allogeneic transplantation, as will be described in detail in this review, it is
      justified to anticipate an increasing role for this modality of treatment in
      relapsed non transplanted patients and as maintenance of the responses achieved
      with chemotherapy at conventional or high doses.

PMID- 10962824
TI  - [Larva migrans: dogs, parasites and man].

PMID- 10962825
TI  - [Hematopoietic progenitor cells in wonderland].

PMID- 10962826
TI  - [Twelve rules of a good clinical history in the era of managed medicine].

PMID- 10962827
TI  - [About numbers and length of a physiological phenomenon].

PMID- 10962828
TI  - [Today. What are total pain and spiritual distress in oncologic patients?].

PMID- 10962829
TI  - A better test for cognitive loss.

PMID- 10962831
TI  - Personality disorder in primary care.

PMID- 10962830
TI  - A woman's demands in antenatal care.

PMID- 10962832
TI  - Safe approaches to treating drug addiction.

PMID- 10962833
TI  - Cognitive therapy: a practical guide.

PMID- 10962835
TI  - What lies behind phobia?

PMID- 10962834
TI  - Understanding the disorders of sexual preference.

PMID- 10962836
TI  - How can you help the bereaved patient?

PMID- 10962837
TI  - Managing UTI in adults.

PMID- 10962838
TI  - Advising the patient who presents with heel pain.

PMID- 10962839
TI  - Diagnosing acute shortness of breath in adult patients.

PMID- 10962840
TI  - A policy at risk from human nature?

PMID- 10962841
TI  - A private medical reveals raised PSA.

PMID- 10962842
TI  - Key developments in cardiovascular medicine.

PMID- 10962843
TI  - The GP's role in acute myocardial infarction.

PMID- 10962845
TI  - When is fetal heart examination justified?

PMID- 10962844
TI  - The new approach to cardiovascular risk.

PMID- 10962846
TI  - ECG quiz.

PMID- 10962847
TI  - Murmurs in adults: when should you take action?

PMID- 10962848
TI  - Managing cardiac arrhythmias. Part I. General principles of investigation and
      management.

PMID- 10962849
TI  - Managing cardiac arrhythmias. Part II. Management strategies for specific cardiac
      arrhythmias.

PMID- 10962850
TI  - 'Doctor, am I fit enough to exercise'?

PMID- 10962851
TI  - Caring for patients wanting a home death.

PMID- 10962853
TI  - [Treatment of Helicobacter pylori infection in patients with duodenal ulcer: a
      cost-benefit study].
AB  - BACKGROUND: Epidemiological differences suggest that treatments for H. pylori
      eradication should be locally validated. AIM: To perform a cost benefit study of
      different treatment options for H. pylori infection. PATIENTS AND METHODS: One
      hundred and sixty-seven patients with active duodenal ulcer and H. pylori
      infection who completed a 2-week treatment with one of the following regimens
      were included: famotidine plus amoxycillin plus metronidazole (FAM), omeprazole
      plus amoxycillin plus tinidazole (OAT) or lansoprazole plus clarithromycin plus
      amoxycillin in 3 (LAC1) or 2 (LAC2) daily doses. We compared efficacy, adverse
      effects and cost. RESULTS: Eradication rate was 74.6, 72.9, 96.4 y 91.7% for FAM,
      OAT, LAC1 and LAC2 respectively (p < 0.05). Direct cost ranged from US$ 50 for
      FAM to US$ 220 for LAC1. A decision analysis was carried out in a model including
      direct and indirect costs and considering retreatment with antibiotics after the
      first treatment failure and one-year treatment with H2-blockers in case of a
      second failure. FAM was selected as the most cost-effective option, with an
      estimated cost of about US$ 300 +/- 148 per patient. However, cost associated to
      LAC2 was very similar (US$ 320 +/- 58) and the lower standard deviation suggests
      less variation. Sensitivity analyses, considering reasonable fluctuation in
      parameters such as eradication rate, cost and follow-up period suggest that a
      regimen containing a proton pump inhibitor, clarithromycin and amoxycillin may be
      the most cost-effective treatment. CONCLUSIONS: These results should be confirmed
      in other settings, specially in ordinary clinical practice, far from clinical
      research.

PMID- 10962852
TI  - [Authorship in manuscripts published in biomedical journals].
AB  - Multiauthorship shows an increasing trend in biomedical and other scientific
      journals. A main concern for editors, reviewers and readers is to find out
      whether all individuals enlisted as authors actually fulfill criteria for
      authorship as defined in the document "Uniform Requirements for Manuscripts
      Submitted to Biomedical Journals". Revista Medica de Chile is addressing this
      relevant topic with a combined strategy: (1) A retrospective analysis of the
      manuscripts published in the recent decades in the Revista will quantify and
      illustrate the local trend in multiauthorship; (2) A "Statement of
      accountability": signed by all authors in manuscripts submitted to the Revista,
      is in use since 1997; and (3) A new form of this "Statement of accountability"
      requests all authors to identify their personal involvement in the work
      represented by the manuscript. This information will be available to every person
      participating in the editorial assessment of the manuscript (editors and external
      reviewers) but during a trial period of six months authors will be allowed to
      object the publication of this data, stating the reasons for this objection.
      After six months the editors will evaluate the information collected and the self
      declared role of every author enlisted. The terms "Author" and "Main author" will
      continue being used to designate participants because "contributor" (replacement
      alternative proposed by Rennie et al., currently in use by several leading
      general medical journals) has a different main meaning in Spanish than in English
      and it might have a negative effect.

PMID- 10962854
TI  - [Immunosenescence: delayed cutaneous hypersensitivity tests in independently
      living Chilean elderly individuals].
AB  - BACKGROUND: Delayed cutaneous hypersensitivity tests are a globally accepted test
      to assess cellular immunity in vivo. The quality and quantity of the response to
      these type of tests, varies in different populations. AIM: To study delayed
      cutaneous hypersensitivity in a group of healthy Chilean elders. MATERIAL AND
      METHODS: Forty two elders (32 male), aged 60 to 76 years old were studied.
      Multitest-CMI was applied in the left forearm. This test allows the subcutaneous
      administration of seven antigens and a glycerin control. Results were compared
      with those of a group of young adults studied by the authors. RESULTS: Among
      males there was a mean of 2.7 +/- 1.4 positive responses compared with women,
      that had 1.7 +/- 1 positive responses (p = 0.016). The sum of response diameters
      was 4.2 +/- 1.5 and 3.6 +/- 1.9 mm in men and women respectively (p = NS).
      Compared to young adults, elderly women had a lower response to tetanus and
      diphtheria toxoids and men had a lower response to diphtheria and Proteus
      mirabilis. CONCLUSIONS: Elderly people have a less intense response to delayed
      cutaneous hypersensitivity tests than young adults. This response must be
      assessed in each population to account for regional variability.

PMID- 10962856
TI  - [Mortality due to congenital malformations in Chile (1969-1997)].
AB  - BACKGROUND: Congenital malformations are defined as those structural, metabolic
      or functional defects found at birth. AIM: To study the mortality due to
      congenital malformations in Chile between 1969 and 1997, their type, individual,
      temporal and geographic variations. MATERIAL AND METHODS: A descriptive analysis
      of deaths registered by the National Statistics Institute and the Ministry of
      Health. Means, frequencies, raw and adjusted rates were calculated and inferences
      for some variables were carried out. RESULTS: Between 1969 and 1997 ther was
      tendency towards a reduction in rates of mortality due to congenital
      malformations and an increment in their relative importance. During the period,
      the risk for chromosome (98%) and osteomuscular (67%) malformations increased.
      Men and children of less than one year had the higher risk. In 1995, 1167 deaths
      due to congenital malformations were registered, 90% in children of less than 5
      years. Higher risks occurred in urban zones (with a rate of 8.25 per 100,000) in
      the third region (rate 11.59) and second region (rate 11.2). Most deaths occurred
      in hospitals (85%). Main causes of death were circulatory system, central nervous
      system and chromosome malformations. CONCLUSIONS: The differences in regional
      deaths due to congenital malformations suggests specific risks that deserve
      further study.

PMID- 10962857
TI  - [Congenital malformations and pesticide exposure].
AB  - BACKGROUND: Chronic pesticide exposure is a recognized risk for human health. The
      frequency of congenital malformations in exposed people, can be used for
      epidemiological studies assessing reproductive risk secondary to toxic exposure.
      AIM: To study the association between the incidence of congenital malformations
      and parent's exposure to pesticides. MATERIAL AND METHODS: A prospective study of
      cases and controls. The exposure could be caused by occupational activities or
      residence around fumigated crops. The records of cases and controls from the
      surveillance carried out in the Hospital Regional de Rancagua were analyzed. This
      hospital is active member of a collaborative study of congenital malformations in
      Latin America. RESULTS: In two years there was a total of 453 newborns (18
      stillborn) with congenital malformations, with an incidence of 41.24/1000.
      Considering only children born alive, the paired analysis of cases and controls
      showed an association of congenital malformations with a history of maternal
      exposure, with an attributable fraction of 54.4%. CONCLUSIONS: These results,
      showing an association between pesticide exposure and congenital malformations,
      should be analyzed in the future by a logistic regression test.

PMID- 10962855
TI  - [Effect of low calcitonin doses on bone remodeling in postmenopausal women with
      high bone turnover rate].
AB  - BACKGROUND: Calcitonin is specially indicated for the treatment of osteoporosis
      in women that cannot receive estrogen replacement therapy or that have a high
      bone turnover rate. AIM: To study the effects of low intranasal calcitonin doses
      on bone remodeling in postmenopausal women with a high bone turnover. PATIENTS
      AND METHODS: Forty one healthy women aged 56 +/- 6 years old, with a mean lapse
      after menopause of 7.6 +/- 6.5 years and with a high bone turnover rate,
      evidenced by an urinary hydroxyproline (mg/dl)/creatinine (g/dl) ratio of 52.4 +/
      7.2, were studied. They were randomly assigned to receive 100 or 50 U/calcitonin
      thrice a week during 3 months or to a control group that received placebo. All
      received 500 mg/day calcium carbonate. Urinary hydroxyproline/creatinine ratio
      was measured a 0, 15, 30, 60 and 90 days. Plasma bone fraction of alkanine
      phosphatases was measured at 0, 30 and 90 days. RESULTS: Initial urinary
      hydroxyproline/creatinine ratio and plasma bone fraction of alkanine phosphatases
      were similar in all study groups and there was no change in these parameters
      during the study period. CONCLUSIONS: Intranasal calcitonin in doses of 100 U
      thrice a week or less, does not modify accelerated bone turnover in
      postmenopausal women.

PMID- 10962858
TI  - [Thyroid cancer. Report of 85 cases].
AB  - BACKGROUND: Thyroid cancer is the most frequent endocrine cancer with important
      implications in terms of diagnosis and treatment. AIM: To report a population of
      patients with thyroid cancer diagnosed by pathological studies of the surgical
      piece. PATIENTS AND METHODS: Eighty five patients (68 female) with the definitive
      diagnosis of thyroid cancer were studied. Clinical, imaginological, cytological
      and pathological findings were analyzed. RESULTS: The age range of patients was
      10 to 77 years old. Sixty nine patients had ultrasonographic studies which showed
      a solid nodule in 84%, mixed solid-cystic area in 14.5% and a purely cystic
      nodule in 1.5% of the cases. Nineteen patients had non specific calcifications.
      Fine needle aspiration cytology was negative for malignancy in eight patients
      (false negative rate of 9.9%). The average size of the nodules was of 2.8 +/- 1.6
      cm). Six nodules measured less than one cm (microcarcinoma). In the initial
      surgical procedure, 13 patients had lymph node metastases, 2 of them had a
      primary tumor of 1 cm and 5 patients had Graves's Disease. Frozen biopsies during
      operation had 9 false negative results for cancer (10.6%). Pathology showed 64
      cases of papillary cancer (75%), 14 of follicular (16.5%), two were Hurthle cell
      cancer (2.4%), three were medullary (3.5%), and two anaplastic (2.4%).
      CONCLUSIONS: In our experience, thyroid cancer is more common in women, solid
      lesions predominate in the ultrasonography and calcifications are frequently
      found. The tumor size is variable and the most frequent pathological type
      corresponds to differentiated cancers. Using the definitive pathological study as
      the standard, the diagnostic sensitivity of fine needle cytology was 90.1%, and
      of frozen section 89.4%.

PMID- 10962859
TI  - [The use of molecular biology techniques in the articles published in Revista
      Medica de Chile].
AB  - BACKGROUND: Molecular biology is a new branch of biological sciences, with novel
      laboratory techniques that are being progressively applied into biomedical and
      clinical research and, furthermore, into medical practice. AIMS: To evaluate the
      use of molecular biology techniques in Chilean biomedical and clinical research
      and its evolution in the recent decade. METHODS: All papers published as research
      articles, clinical experiences or case reports, in Revista Medica de Chile,
      during two time periods: 1987-1989 and 1997-1999, were reviewed to find out
      whether molecular biology techniques had been used or not. This journal publishes
      roughly 40% of papers generated in Chile, in biomedical or clinical topics, while
      another 15% appears in foreign journals. RESULTS: Among 341 papers published in
      1987-1989, 57 (16.7%) had used one or more molecular biology techniques; in
      contrast, among 318 papers published in 1997-1999, 91 (28.8%) had used them (p <
      0.001). Most papers using molecular biology techniques were research articles.
      Immunology, genetics, endocrinology, hematology, hepatology and rheumatology were
      the specialties providing a greater number and proportion of papers using
      molecular biology techniques. Chilean universities were the main institutions
      sponsoring these articles and FONDECYT (the Chilean Government Research Granting
      Office) was the main source of funding. The University of Chile (State-owned)
      provided most centers where these publications had been generated, followed by
      the Pontifical Catholic University of Chile. CONCLUSIONS: Molecular biology
      techniques have been rapidly and progressively incorporated as research tools in
      biomedicine and clinical medicine, in Chile. At the present time, these
      techniques are predominantly used in research conducted in University settings
      and funded by Governmental research grants.

PMID- 10962860
TI  - [Detection and characterization by ultrasonography of soft tissue foreign
      bodies].
AB  - BACKGROUND: Soft tissue foreign bodies are a frequent cause of consultation in
      emergency rooms. It is difficult to verify their existence since conventional
      radiology only detects radio opaque objects. Ultrasound can be a useful
      diagnostic procedure. AIM: To report our experience in the detection of soft
      tissue foreign bodies by ultrasound examination. PATIENTS AND METHODS: The
      ultrasonographic appearance of vegetables, glass and plastic, metal, bone and
      stones was studied in gelatin preparations. In a second stage, 52 patients (27
      male, aged 3 to 88 years old) were studied, in whom the presence of a soft tissue
      foreign body was confirmed surgically. RESULTS: The mean error of the procedure
      for the assessment of foreign body size was 0.2 mm in vitro and 0.5 mm in vivo.
      The deepness and involved planes were correctly diagnosed in 96%, the number of
      fragments were diagnosed correctly in 94% of cases. The type of foreign body was
      identified correctly in 77% of cases and complications were detected in 100% of
      cases. CONCLUSIONS: Ultrasound is a sensitive and accurate method for the
      detection of soft tissue foreign bodies.

PMID- 10962861
TI  - [Severe apnea: an early sign of Pneumocystis carinii pneumonia in an HIV-negative
      infant].
AB  - A few reports in the medical literature suggest an association between
      Pneumocystis caring and apnea in small infants. This patient, a 1 month 20 days
      old, HIV negative, infant girl weighing 2,000 grams was admitted to hospital
      after presenting a severe episode of apnea with cyanosis and bradycardia. She
      progressively developed bronchopneumonia by P. carinii that required prolonged
      mechanical ventilation with high ventilatory parameters. The clinical course of
      this patient illustrates that apnea can be an early sign of P. carinii infection
      in small infants. Early diagnosis and specific therapy might prevent morbidity
      and mortality and also decrease the length of hospitalization.

PMID- 10962862
TI  - [Distribution of financial resources according to the productivity (determined by
      bibliometry) in the Medical Research Laboratories of the Hospital das Clinicas da
      Faculdade de Medicina da Universidad de Sao Paulo (Brazil)].
AB  - A challenge that research managers have to face is how to "reallocate" agency
      budgets in order to bring them in line with the results of performance reviews.
      Research policies must develop a strategic plan describing their goals, devise
      yardsticks to measure their progress, and tie that performance to allocate
      research funds with some degree of priority. Though Brazil already has a
      substantial presence in world's science, scientific enterprise must be used to
      strengthen it. The first step should be to raise standards in Brazilian science
      by concentrating the resources on supporting excellence. A strategy to judge
      biomedical research productivity should include tactics to disclose whether the
      resulting publications have appeared in the field's most respected, peer-reviewed
      journals. A pilot project to road-test the above-discussed ideas on performance
      measurements was conducted at the Laboratories of Medical Research (Clinical
      Hospital, University of Sao Paulo School of Medicine). These Laboratories perform
      a vast proportion of biomedical research at the country's largest University.
      This article illustrates that confidence in fairness and consistency with which
      funds are now being allocated has helped to improve productivity, thus showing
      that this strategy is fruitful.

PMID- 10962863
TI  - [Molecular nutrition, role of the PPAR system in lipidic metabolism and its
      importance in obesity and diabetes mellitus].
AB  - PPARs are transcription factors belonging to the super family of hormonal
      receptors. Their activity is regulated by fibrates, thiazolidinediones, certain
      anti inflammatory drugs and fatty acid derivatives, present in food. PPAR
      isoforms play a central role in lipid homeostasis, regulating anabolic (PPAR
      gamma) and catabolic (PPAR alpha) pathways of lipid metabolism. Additionally,
      these receptors participate in glucose homeostasis, influence cellular
      proliferation and differentiation and participate in inflammatory processes. The
      effects of PPARs on oxidative substrate partitioning suggests that they have a
      relevant role in the development of obesity and insulin resistance.

PMID- 10962864
TI  - [Susceptibility to varicella-zoster virus infection, in pregnant adolescents of
      the Northern Area of Santiago, Chile].

PMID- 10962865
TI  - [P53 gene mutation in gallbladder cancer].
AB  - BACKGROUND: Gallbladder cancer frequency and mortality renders it one of the most
      important neoplastic diseases in Chile. P53 tumor suppressor gene has been
      studied in most types of cancer, but there is scarce information about it in
      gallbladder cancer. AIM: To study the frequency of P53 gene mutation in
      gallbladder cancer in the ninth region of Chile. MATERIAL AND METHODS: In 25
      pathological samples of gallbladder cancer, the direct amplification and
      sequencing of p53 gene exons 5,6,7,8-8 was possible. RESULTS: Seventeen punctual
      mutations were observed in 13 cases (52%). There were 10 transitions, 5
      transversions, one insertion (codon 194) and one deletion (codon 186). Eight
      cases had mutations in exon 5, six had mutations in exon 6, two had mutations in
      exon 7 and one had mutations in exons 8-9. In 14 of 25 cases, gene p53 protein
      was positive. When immunohistochemical expression of gene p53 protein was
      positive in more than 20% of cells, there was a high correlation between genetic
      alterations and immunohistochemical expression of the protein, with a
      specificity, sensitivity, positive and negative predictive values over 80%.
      CONCLUSIONS: P53 gene mutation is observed in a high proportion of gallbladder
      cancers at it can be accurately detected with conventional immunohistochemical
      techniques. The importance of this gene in the genesis of this carcinoma should
      be determined studying preneoplastic lesions and early carcinomas.

PMID- 10962866
TI  - [Helicobacter pylori and chronic gastritis: relationship between infection and
      inflammatory activity in a high risk population for gastric cancer].
AB  - BACKGROUND: Helicobacter pylori has been involved in gastric epithelial cell
      damage and gastric gland loss or atrophy. AIMS: To evaluate role of Helicobacter
      pylori infection in acute and chronic changes of chronic gastritis in a high
      gastric cancer-risk population. MATERIAL AND METHODS: 200 patients with chronic
      gastritis were selected from pathological files of Temuco Hospital. A complete
      histopathological protocol was fulfilled considering the presence of infection by
      Helicobacter pylori-like-organism (HLO), acute and chronic inflammatory
      infiltrate, epithelial cell damage and epithelial cell regeneration. RESULTS: 82%
      of patients showed infection by HLO. Moreover, this infection reached a frequency
      of 92.7% in gastric ulcer patients and 94.4% in duodenal ulcer patients. A
      statistically significant positive correlation was found between HLO infection
      and polymorphonuclear infiltrate, lymphocytic infiltrate, mucus depletion and
      epithelial regenerative activity. There was not a statistical correlation between
      HLO infection and atrophy. Finally, 90% of patients with multifocal atrophic
      gastritis and 100% of patients with diffuse antral gastritis had HLO infection.
      CONCLUSIONS: HLO gastric infection frequently caused acute inflammatory changes
      in gastric mucosa with chronic gastritis. Sometimes these changes were severe,
      with marked polymorphonuclear migration throughout epithelium and severe
      epithelial cell damage. Recovery of these changes could be considered as a goal
      in Helicobacter pylori eradication therapy decision.

PMID- 10962867
TI  - [Community acquired pneumonia: from intravenous to oral cephalosporin sequential
      therapy].
AB  - BACKGROUND: Many hospitalized patients with community acquired pneumoniae can be
      switched early in the course of therapy from intravenous to oral antibiotics,
      when there are subjective and objective indicators of improvement. This modality
      of treatment is called "switch therapy". AIM: To compare sequential therapy using
      an oral third generation cephalosporin, with conventional therapy using
      intravenous ceftriaxone in community acquired pneumonia. PATIENTS AND METHODS:
      Forty patients admitted due to community acquired pneumonia, initially treated
      with ceftriaxone 1 g/day i.v. and that showed clinical improvement after three
      days of therapy, were studied. They were randomly assigned to continue
      intravenous therapy with ceftriaxone for a total of 10 days or switched to
      ceftibuten 400 mg od for seven days. RESULTS: Twenty one patients continued i.v.
      treatment and 19 were switched to ceftibuten. There were no differences between
      both groups in terms of clinical cure, radiological improvement or normalisation
      of white blood cell count. CONCLUSIONS: Patients with community acquired
      pneumonia that have a good initial response to intravenous antimicrobials, can be
      safely switched to oral therapy. This therapy will shorten hospital stay and
      thereby treatment costs.

PMID- 10962868
TI  - [Anti LKM-1 antibodies and cryoglobulinemia in autoimmune chronic hepatitis and
      virus C hepatitis].
AB  - BACKGROUND: Anti liver kidney microsome antibodies (LKM-1) have been recently
      incorporated to the study and classification of chronic autoimmune hepatitis (HC
      A1). The presence of anti LKM-1 antibodies and essential cryoglobulinemia is
      frequent in virus C associated chronic hepatitis (HC-VC). AIM: To study the
      frequency of anti LKM-1 antibodies and cryoglobulin levels in patients with HC
      AI, HC-VC and cryptogenic cirrhosis. PATIENTS AND METHODS: Forty-two patients
      were studied. Nineteen adult women with classic HC-AI with positive antinuclear
      or anti smooth muscle antibodies. Five patients of less than 20 years old with HC
      AI and negative antinuclear and anti smooth muscle antibodies. Ten adult women
      with cryptogenic cirrhosis, 4 women and 4 men with HC-VC. Serum samples were
      obtained at 37 degrees C. Antinuclear, anti smooth muscle and anti LKM-1
      antibodies were measured by indirect immunofluorescence using Hep-2 cells and rat
      tissue slices as substrates. Cryoglobulins were determined by the traditional
      method and cryocrit. RESULTS: All studied patients were anti LKM-1 negative. All
      had significant circulating cryoglobulin levels. CONCLUSIONS: In this sample of
      patients with HC-AI or HC-VC, anti LKM-1 antibodies were not detected but all had
      cryoglobulinemia.

PMID- 10962870
TI  - [Familial recurrence of non syndromic cleft lip with or without cleft palate in
      Chilean populations].
AB  - BACKGROUND: The presence of major genes in the susceptibility of non syndromic
      cleft lip with or without cleft palate (CL/P) in Chile has been postulated,
      considering the high prevalence and familial aggregation of this condition. AIM:
      To study the familial recurrence of CL/P in Chile. PATIENTS AND METHODS: The
      recurrence risk of CL/P was studied in 217 extended pedigrees where 33 (15.2%)
      were multiplex (21 male and 12 female propositi). These multiplex extended
      pedigrees (with more than one affected individual) represented 75 nuclear
      pedigrees, constituted by 840 males and 803 females and are the basic information
      of this study. RESULTS: A significantly higher frequency of affected males
      (4.15%) than affected females (2.27%) was observed, independent of the difference
      in number of propositi by sex. Even though no differences were observed between
      families where both parents were unaffected, compared to those with only one
      affected parent, a higher proportion of affected descendants was found when the
      affected propositi was the mother. In multiplex families, the recurrence risk,
      according to the genetic proximity to the proband, was 10.1, 3.6 and 3.3%
      respectively for first, second and third degree relatives. The figures were 1.5,
      0.5 and 0.4% respectively, when adjusted to the 217 extended pedigrees.
      Considering that the risk for the general population in Chile is approximately
      0.16%, it is 10.3, 3.2 and 2.6 times higher among affected families. CONCLUSIONS:
      The high heritability of CL/P and the risk encountered for the Chilean population
      supports the hypothesis of major genes involved in its susceptibility.

PMID- 10962869
TI  - [Prevalence of asthma in Chilean students. Descriptive study of 24,470 children.
      ISAAC-Chile].
AB  - BACKGROUND: There is little information about the prevalence of asthma in Latin
      American children. AIM: To determine the prevalence of asthma among Chilean
      school age children. SUBJECTS AND METHODS: The prevalence of respiratory symptoms
      related to asthma in schoolchildren aged 7 and 13 years, coming from South
      Santiago, Central Santiago, Valdivia and Punta Arenas, was determined using the
      methodology of the International Study on Asthma and Allergies in Childhood
      (ISMC). A random sample of school children aged 6-7 and 13-14 years from each
      locality was selected. This resulted in 24)470 surveyed children (11,723 aged 6-7
      years and 12,747 aged 13-14 years). RESULTS: The current prevalence of wheezing
      ("wheezing in the last 12 months") ranged from 16.5% to 20.0% in children aged 67
      years, and from 6.8% to 11.7% in children aged 13-14 years. The cumulative
      prevalence of asthma ("asthma ever"), ranged from 9.7% and 16.5% in the 6-7 years
      group and from 7.3% to 12.4% in those aged 13-14 years. CONCLUSIONS: This study
      found much higher figures for prevalence of respiratory symptoms related to
      asthma in school children than those previously reported in this country, with a
      significant variability between centers (p < 0.05). The prevalence of asthma in
      Chilean schoolchildren is as high and variable as that reported in industrialized
      countries.

PMID- 10962871
TI  - [Improving the quality of clinical interview teaching: evaluation of an
      intervention with medical students].
AB  - BACKGROUND: Quality of clinical interview is a key issue both for patient
      satisfaction and for diagnostic efficiency. Its adequacy relates to better
      clinical diagnosis treatment plans and patient compliance. AIM: To measure the
      quality of interviews performed by medical students in three Chilean medical
      schools before receiving specific training on the subject and to compare the
      scores obtained after introductory courses on interview. MATERIAL AND METHODS:
      The interviews were videotaped and then evaluated using an objective scale, that
      measures 33 skills grouped in six areas: opening, problem exploration, non verbal
      facilitation, interpersonal patient reaction and closing. The students were
      assigned to an experimental group that received an interactive workshop with role
      plays, vignettes and videotape feedback, and to a non intervention group that
      received the usual bedside training on medical interviews. RESULTS: Both groups
      shared the same skill level before the training, with better scores on nonverbal,
      patient reaction and problem exploration, and worse ones on closing and
      interpersonal skills. Comparing pre and post-test results, the overall score
      improved in the experimental group (from 33.2 to 38.3, p = 0.002) and worsened
      among non intervened students. There were statistically significant changes for
      opening (p < 0.002), problem exploration (p < 0.05), non verbal facilitation (p <
      0.0001) and closing (p < 0.0001). CONCLUSIONS: It is important to train students
      not only in specific knowledge contents but in the process of interview. This
      training should encourage the development of empathy and closing skills.

PMID- 10962872
TI  - [Prognostic value of Sharp's index in the clinical and laboratory response to an
      intravenous methylprednisolone pulse in patients with rheumatoid arthritis].
AB  - BACKGROUND: No reliable variables to predict clinical or laboratory response to
      treatment in patients with rheumatoid arthritis were available until recently.
      AIM: To asses the potential predictive value of the Sharp's modified radiographic
      joint damage index for the assessment of clinical and laboratory response to a
      methylprednisolone i.v. pulse. PATIENTS AND METHODS: Twenty-two patients
      suffering from rheumatoid arthritis received a single i.v. pulse of 1 g of
      methylprednisolone. Hand X-rays were taken at baseline and blindly scored by two
      trained radiologists. Clinical and laboratory variables were assessed at baseline
      and at weekly intervals up to 30 days plus a 60 days final evaluation.
      Improvement was defined as a 50% amelioration in 4 variables. RESULTS: Assessment
      of radiographic scores had a high correlation between and within observers
      (intraclass correlation = 0.998). Sharp score did not reach statistical
      significance as global predictor for the inflammatory variable response to
      methylprednisolone. However, when the number of swollen joints was taken into
      account, patients with a low erosive score (Sharp < or = 50) had a more prolonged
      clinical response, than patients with higher erosive score (Sharp > 50) (Fisher
      test p = 0.023). It is of clinical importance to point out that among patients
      with high Sharp score there were also responders who reached a high level of
      improvement. A statistically significant correlation between the basal PCR serum
      titers and the radiographic score (p < 0.02) was observed. CONCLUSIONS: The
      number of swollen joints and other variables that consider joint structural
      changes should be considered for the assessment of rheumatoid arthritis patients.

PMID- 10962873
TI  - [Medical-surgical experience of intestinal intussusception. Experience of a
      university institution].
AB  - BACKGROUND: Management of intestinal intussusception in children has evolved from
      exclusively surgical treatments to nonoperative reduction under fluoroscopic
      monitoring. AIM: To report a 10 year experience in a University Hospital in the
      management of intestinal intussusception. PATIENTS AND METHODS: Seventy two
      patients, aged 2 to 72 months of age, with an uncomplicated intussusception, that
      were treated by barium or air enema, were studied. RESULTS: The success rate was
      73% with barium reductions, and 100% with air reductions. In 17 patients (24%),
      enema reduction was unsuccessful and were subjected to a surgical reduction.
      CONCLUSIONS: Nonsurgical reduction is safe and effective as the initial treatment
      of uncomplicated intussusception in children.

PMID- 10962874
TI  - [Acute poisoning with methotrexate used as an abortifacient: description of 2
      cases].
AB  - Acute intoxication with methotrexate, used as an abortive, has not been described
      in Chile. We report two female patients, aged 15 and 24 years old, who presented
      with mucositis, erythrodermia, pancytopenia, and elevation of hepatic enzymes.
      Plasma methotrexate levels confirmed the clinical diagnosis and both patients
      were treated with high leucovorin doses and management of associated
      complications. In one patient, pregnancy continued, giving birth to a newborn
      with cranial, face and limb malformations. The second patient had a late rescue
      with leucovorin and was discharged with a persistent sensory motor neuropathy.
      Considering the severity of complications and that patients may deny its use,
      when there is reasonable clinical suspicion of methotrexate intoxication,
      leucovorin treatment should be started.

PMID- 10962875
TI  - [Intracranial mucocele. Report of a case].
AB  - Mucocele, usually associated to paranasal sinuses is defined as an abnormal
      accumulation and retention of mucous secretions. It usually presents with
      intraorbital or paranasal and rarely with pure neurological symptoms. We report a
      41 years old male who presented with a history of supraorbital left headache,
      diplopia and proptosis. CT scans and magnetic resonance imaging showed an
      expansive mass in the right frontal sinus. The patient was operated, the
      presumptive preoperative clinical diagnosis of mucocele was confirmed and the
      lesion was drained. A postoperative CT scan confirmed the normal expansion of the
      frontal lobe.

PMID- 10962876
TI  - [Vegetal foreign body in the airway: an unusual cause of hemoptysis in childhood.
      Clinical case].
AB  - Hemoptysis is an infrequent symptom in childhood and potentially life
      threatening. The most common causes in this age group are bronchiectasis
      secondary to cystic fibrosis, cardiovascular and pulmonary congenital anomalies
      and a miscellaneous group of causes including retained intrabronchial aspirated
      foreign bodies. We report a previously healthy 5-year-old girl with recurrent
      pneumonias associated with episodes of hemoptysis. She was admitted in our
      institution to investigate the persistence of hemoptysis. Based on clinical
      history, aspiration of a vegetal foreign body was postulated as the etiology and
      it was confirmed in the pathological examination after surgical exploration, with
      pulmonary lobe resection. The importance of a good history taking in pediatric
      hemoptysis is emphasized.

PMID- 10962877
TI  - [Is type-2 adult diabetes a variety of idiohypophyseal diabetes? A proposition
      that opens perspectives].
AB  - The advances in the study of the role of growth hormone (GH) in the field of
      diabetes, confining clinically its glucoregulatory and diabetogenic effects, plus
      relevant findings in basic research, open new perspectives. The influence of GH
      on Type-2 diabetes is based on the classic experiments of Houssay's school, the
      diabetogenic action of GH and its transferrin mediator. Since GH is under
      hypothalamic command, the permanent GH hypersecretion is the pathophysiological
      evidence for hypothalamic dysfunction. Thus, type-2 diabetes is postulated as a
      reversible type of clinical idiohypohyseal diabetes. Different degrees of
      hypophyseal diabetes can be observed, with the interplay between insulin-growth
      factor-l and transferrin in some cases of acromegaly. In cases of selective
      predominance of GH and the consequent chronic elevation of transferrin levels,
      idiohypophyseal diabetes would develop. Therefore, this type of diabetes should
      be treated with hypothalamic GH inhibitors. In this line of thinking, the use of
      somatostatin analogs looks promising.

PMID- 10962879
TI  - [Arterial hypertension in Chilean aborigines].

PMID- 10962878
TI  - [Bronchial asthma and atopic diseases as an emerging problem in public health:
      new etiological hypothesis. The experience of developed societies].
AB  - Developed countries report increasing trends in the prevalence of asthma and
      atopic diseases over the last 40 years. This change cannot be attributed to
      artefactual effects. Emerging from these information, new approaches have been
      generated to explore these novel findings. Among the most important new factors
      to be explored, scientific research is pointing out to variables related with
      physical environment, socio-economic and genetic background, anthropometry at
      birth, nutritional status, diet, exercise and hormonal profile. Changes in the
      epidemiology of asthma and atopic conditions in developed countries were also
      preceded by increases in the prevalence of chronic diseases and their risk
      factors. Chile does not have information about time trends on these diseases, but
      several studies are reporting a high prevalence of asthma among adults.
      Conversely, results from the collaborative ISAAC study carried out in children,
      have shown a relative low prevalence of asthma in Chilean children. An increasing
      trend in chronic diseases and their risk factors has been reported in Chile,
      suggesting an epidemiological pattern similar to that experienced by
      industrialised countries, when the prevalence of asthma and atopic began to
      increase. This article review current information about etiological research
      emphasising the need to develop local research on asthma and atopic diseases
      taking into account our epidemiological situation.

PMID- 10962880
TI  - [Gastric cancer and tumor growth regulation. Study of cell proliferation markers
      and protein complex p53/p21WAF1/CIP1/mdm-2].
AB  - BACKGROUND: p53/p21WAF1/CIP1 and mdm-2 proteins play an important role in cell
      cycle regulation. The study of the pathogenesis of gastric cancer is important to
      understand how these tumors progress during their natural history. AIM: To study
      the relationship between the immunohistochemical expression of p53/p21WAF1/CIP1
      and mdm-2 and cell proliferation in gastric cancer. MATERIAL AND METHODS: Fifty
      one gastrectomy specimens with gastric cancer were studied using
      immunohistochemistry for p53/p21WAF1/CIP1 and mdm-2. Cell proliferation was
      determined by immunolabelling with PCNA and Ki67 antigens. Mitosis figures were
      counted in 10 high power microscopic fields. RESULTS: Patients from whom gastric
      cancer specimens were obtained had a mean age of 59.3 years. Ki67 and mitosis
      counting showed the highest correlation index with proliferation indexes studied.
      No correlation was found between the expression of protein complex
      p53/p21WAF1/CIP1 and mdm-2 and morphological characteristics of gastric tumors.
      Mdm-2 protein overexpression was the only marker that showed an independent
      correlation with cell proliferation. Moreover, mdm-2 positive tumors showed the
      highest proliferation indexes when p53 was not immunohistochemically over
      expressed, as determined by PCNA labelling index. CONCLUSIONS: In gastric cancer,
      a direct correlation between mdm-2 overexpression and cell proliferation was
      observed. Moreover, the fact that mdm-2 positive tumors showed the highest cell
      proliferation when p53 was not overexpressed, entitles us to hypothesize that mdm
      2 overexpression could play a major role in gastric carcinogenesis.

PMID- 10962881
TI  - [Breast cancer risk factors in women in Santiago, Chile].
AB  - BACKGROUND: Epidemiological studies suggest a relation between breast cancer,
      diet and life styles. AIM: To analyze the association between food patterns,
      obesity, smoking, alcohol consumption and breast cancer risk in women of
      Santiago. PATIENTS AND METHODS: A case-control study design (170 cases and 340
      controls), matched by age and sex, was used. Through a food frequency
      questionnaire the average daily intake of vegetables, fruits, beta-carotene,
      vitamin A, C, E and fiber was analyzed. Other exposures to non-nutritional risks
      (parity, smoking, cancer history) were also studied. Conditional logistic
      regression was calculated to determine the odds ratio associated with variations
      in food and nutrient intake and non-nutritional factors. RESULTS: Cases had a
      greater BMI and a higher prevalence of obesity than controls (p < 0.02). No
      differences were observed in either group food patterns. The ORs for breast
      cancer associated with obesity and alcohol consumption were 1.65 (95% CI 1.06
      2.64) and 1.61 (95% CI 1.06-2.54) respectively (p < 0.05). Multiparity had a
      protective effect with 0.66 less risk (95% CI 0.44-0.99). No protective effect
      associated to a greater intake of vegetables, fruits or natural antioxidants was
      observed. Multivariate analysis model disclosed obesity as a risk factor (OR
      1.79, p < 0.02) and parity > or = 4 as protective (OR 0.62, p < 0.02).
      CONCLUSIONS: This study does not support a protective role for natural
      antioxidants against breast cancer but indicate a weak association with obesity.

PMID- 10962882
TI  - [Bone turnover in lactating adolescent: evaluation at the end of pregnancy,
      during and after the weaning period].
AB  - BACKGROUND: There is paucity of information about bone metabolism during
      pregnancy or breast feeding in teenagers. AIM: To study bone turnover at the end
      of pregnancy and during breast feeding in teenagers and correlate it with
      environmental, hormonal or nutritional variables. SUBJECTS AND METHODS: Thirty
      teenagers during their breast feeding period after a first pregnancy and 30
      nulliparous girls matched for age, age of menarche and body mass index were
      assessed three weeks after delivery (period 1), at six months of breast feeding
      (period 2) and one year after the lactating period (period 3). Calcium intake and
      plasma calcium, phosphorus, alkaline phosphatases, parathormone, estradiol and
      prolactin were measured. Calcium, creatinine and hydroxyproline were also
      measured in a morning urine sample. RESULTS: Lactating and control girls were
      aged 16.3 +/- 0.8 and 16.1 +/- 0.7 years old respectively. Calcium intake in
      lactating and control girls was 798 +/- 421 and 640 +/- 346 g/day respectively in
      period 1, 612 +/- 352 and 592 +/- 309 mg/day in period 2 and 495 +/- 180 and 456
      +/- 157 g/day in period 3. During periods 1 and 2, lactating girls had higher
      alkaline phosphatases (161 +/- 37 compared to 119 +/- 28 U/l and 149 +/- 37
      compared to 106 +/- 23 U/l), parathormone (4.3 +/- 2.6 compared to 2.8 +/- 0.8
      ng/dl and 3.6 +/- 1.6 compared to 3.0 +/- 0.9 ng/dl) and urinary hydroxyproline
      (95 +/- 16 compared to 63 +/- 15 mg/g creatinine and 84 +/- 19 compared to 59 +/-
      15 mg/g creatinine). No differences were observed in period 3. No correlation
      between bone turnover variables, body mass index or hormonal parameters, was
      observed. CONCLUSIONS: In teenagers, there is an increase in bone turnover at the
      end of pregnancy, that persists during the lactating period. These changes are
      not related to nutritional or hormonal variables.

PMID- 10962884
TI  - [Prevalence of congenital malformations at birth and associated factors in Easter
      Island, Chile (1988-1998)].
AB  - BACKGROUND: Consanguinity plays an important role in the genetic etiology of
      congenital malformations. In Easter Island the degree of consanguinity could be
      higher than in continental Chile. Therefore the study of the prevalence of
      congenital malformations in this island seems worthwhile. AIM: To study the
      prevalence of congenital malformations at birth in Easter Island. MATERIAL AND
      METHODS: A review of personal and family features of all children born alive
      between 1988 and 1998 in the Rapa Nui Hospital of Easter Island. RESULTS: During
      the study period, 772 newborns were reviewed and 22 were found to have congenital
      malformations. Among the latter, birth weight fluctuated between 3001 and 4000 g
      and the male/female ratio was 0.54. No differences in maternal age between
      children with and without malformations was observed. Heart and circulatory
      malformations, hemangiomas and Down syndrome were the predominant malformations.
      CONCLUSIONS: The prevalence of congenital malformations at birth in Easter Island
      is similar to that of continental Chile. No neural tube defects were detected in
      this sample.

PMID- 10962883
TI  - [Relationship between leptin and insulin blood levels in obese and lean Chilean
      women].
AB  - BACKGROUND: Leptin, a product of ob gene and insulin blood levels, are
      proportional to the amount of adipose tissue. Insulin could have an independent
      regulatory effect on leptin secretion. AIM: To assess the relationship between
      serum leptin and plasma insulin levels in obese and lean Chilean women. MATERIAL
      AND METHODS: One hundred forty five women, aged 20 to 60 years old, were studied.
      Weight, height, waist and hip circumference, fasting blood glucose, insulin and
      leptin levels were measured. Insulin resistance was assessed using the
      homeostasis model assessment. The relationship between different variables was
      determined using multiple linear regression, variance analysis and non parametric
      correlation. RESULTS: Leptin serum concentrations were positively correlated with
      body mass index, insulin plasma levels and degree of insulin resistance. The
      association of leptin with insulin was independent of body mass index and
      persisted after adjustments by body fat distribution and age. CONCLUSIONS:
      Insulin and insulin resistance are associated to high blood leptin levels and
      this association is independent of the degree of adiposity and body fat
      distribution.

PMID- 10962885
TI  - [Eosinophilic colitis caused by allergy to cow's milk protein].
AB  - Eosinophilic colitis is one of the clinical manifestations of allergy to cow's
      milk during the first year of life. We report a series of 9 infants who, under 9
      months of age and while clinically well, presented rectal bleeding of variable
      magnitude, with or without diarrhea, shortly after a cow's milk-based formula was
      initiated (n = 6); yet, 3 cases received only breast feeding. Bleeding
      disappeared in all patients after milk withdrawal from the diet. Challenges were
      planned after 12 months of treatment; three patients have not yet reached this
      moment, 3 had a negative challenge at 12, 18 and 28 months of age and are on a
      complete diet, and 3 are still on cow's milk free diet because ingestion of milk
      at 12, 18 and 25 months still induced rectal bleeding. This series of patients
      gathered in 3 years, follows the trend reported in many countries that there is a
      relative increase of patients diagnosed with allergy conditions early in life.

PMID- 10962886
TI  - [Client categorization: a tool to assess nursing workload].
AB  - BACKGROUND: Client categorization is a management tool that allows an objective
      and structured assessment of the care demands imposed by patients and nursing
      workloads. AIM: To characterize the need for direct nursing care of patients
      admitted to a university hospital. PATIENTS AND METHODS: During two months, all
      patients admitted to intensive, intermediate care units and general services were
      categorized, their need for nursing care and the time invested by nurses in their
      care was registered. All patients were classified as maximal, high, median or low
      risk and as independent, totally or partially dependent on nursing care.
      Considering four degrees of risk and three degrees of dependency, 12 categories
      of patients were defined. RESULTS: Patients admitted to intensive care units were
      of maximal risk and totally dependent and required 1 nurse per 2.2 patients.
      Those admitted in intermediate care units required 1 nurse per 3.8 patients and
      those in general services, 1 nurse per 11.5 patients. CONCLUSIONS: Client
      categorization is a reproducible method that determines a standard measuring unit
      to define nursing needs. This allows the comparison of workloads between
      different services within a hospital or between hospitals.

PMID- 10962887
TI  - [Causes of male infertility. The contribution of the endocrine factor].
AB  - BACKGROUND: Male infertility is responsible for 35% of infertile couples. AIM: To
      investigate the causes of male infertility and the relative importance of
      endocrine factors. PATIENTS AND METHODS: Patients referred to an andrology clinic
      due to an abnormal spermiogram were studied. A testicular examination,
      spermiogram and determination of FSH, LH, testosterone and prolactin were done to
      all. Testicular biopsy was done to patients with severe oligospermia or
      azoospermia. Causes of infertility were defined and classified as pretesticular,
      testicular, posttesticular or unclassified. RESULTS: Two hundred fifty seven
      males were studied. In 3.5% of them, the cause of infertility was defined as
      pretesticular (that included hypothalamic and pituitary endocrine causes), in
      66.9% it was classified as testicular, in 15.6% as posttesticular and in 14%, as
      unclassified. Thirty percent of infertility cases were idiopathic, 17.9% were
      associated to varicocele, 12.8% were associated to cryptorchidism, 8.9% to
      Klinefelter syndrome and 6.6% to exposure to toxic substances. In 50% of patients
      with cryptorchidism, this abnormality was found during the specialized
      andrological examination and referrals for surgical correction were made late.
      Two thirds of patients with Klinefelter syndrome were hypoandrogenic.
      CONCLUSIONS: Causes for male infertility should be investigated and diagnosed
      accurately. Primary hypoandrogenic testicular failures must be treated with
      hormone replacement therapy.

PMID- 10962888
TI  - [Change in metabolic risk factors in obese patients in treatment].
AB  - BACKGROUND: Obesity is a threat to health due to its association with
      cardiovascular risk factors. AIM: To assess the change in metabolic risk factors
      after weight reduction in obese patients. PATIENTS AND METHODS: A retrospective
      analysis of 277 obese patients (198 female) aged 39.5 +/- 12 years old, that
      completed a six month treatment period, consisting in a calorie restricted diet
      (800-1200 Kcal/day), physical activity, education and group psychological
      counseling. At the beginning and at the end of the program, weight, waist
      circumference, resting energy expenditure (REE), serum lipid profile, plasma
      glucose and plasma insulin levels were measured. RESULTS: During the treatment
      period, body mass index decreased from 38 +/- 7 to 33.2 +/- 6.4 kg/m2 with a
      weight loss of 11.7 kg, waist circumference decreased from 106.6 +/- 14.6 to 93.9
      +/- 13.5 cm, REE decreased from 1774 +/- 383 to 1585 +/- 267 Kcal/day, blood
      glucose fell by 5.8%, plasma insulin fell by 40.4%, total cholesterol fell by
      7.5%, LDL cholesterol fell by 8.7%, triglycerides fell by 26.6%, and total
      cholesterol/HDL ratio fell by 12.2%. CONCLUSIONS: Weight loss was associated with
      improvement in metabolic cardiovascular risk factors in obese patients.

PMID- 10962890
TI  - [Serous peritoneal papillary tumor of low malignancy potential. Report of a
      case].
AB  - Papillary serous carcinoma with low malignant potential, similar to those
      described in the ovary, can also originate in the peritoneum. Characteristically
      they show peritoneal spread without involvement of the ovary and, if present, it
      corresponds to a superficial implant similar to those seen in the rest of the
      peritoneal cavity. Histologically they correspond to a low malignant potential
      tumor; they are slow growing and have good prognosis. They are common in young
      women, usually they present few symptoms and are frequently discovered during
      other surgical procedures. The treatment is surgical and it can be conservative
      in cases of women who want to preserve their fertility, without coadjuvant
      therapy. We report a 34 years old woman with a primary peritoneal serous
      carcinoma with low malignant potential and discuss its management.

PMID- 10962889
TI  - [Acute coronary syndrome associated with Chlamydia pneumoniae pneumonia in two
      cases].
AB  - Epidemiological and clinical studies attribute to Chlamydia pneumoniae infections
      a pathogenetic role in atherosclerotic vascular lesions. We report two patients
      in whom this infection was followed by acute coronary events. A 51 years old male
      presented with a right lower lobe pneumonia and a positive immunofluorescence
      serology for Chlamydia pneumoniae, with a IgM titer of 1/64. On the second day of
      evolution, he experienced an acute myocardial infarction. A coronary
      arteriography demonstrated a 80% obstruction of anterior coronary artery and an
      angioplasty was performed. A 84 years old male was admitted with a right lower
      lobe pneumonia and a positive serology for Chlamydia pneumoniae, with an IgM
      titer of 1/32. On the fourth day of evolution, he developed unstable angina with
      electrocardiographic changes. A coronary arteriography demonstrated a three
      vessel disease. In both cases, a tight chronological association was observed
      between Chlamydia pneumoniae infection and acute coronary events.

PMID- 10962891
TI  - [Erythrocytosis post kidney transplantation and its pharmacological treatment:
      angiotensin converting enzyme inhibitors or angiotensin receptor blockers in a
      case].
AB  - A 35 years old male is presented. Eight months after receiving a renal allograft
      his hypertension worsened and his packed red cell volume raised to 53.7%
      Enalapril was started and a 500 ml phlebotomy was performed. In three occasions
      packed red cell volumes decreased excessively and enalapril was discontinued.
      Finally, the drug was replaced with losartan, normalizing blood pressure values
      and stabilizing packed red cell volumes. This case illustrates the different
      reductions in packed red cell volumes induced by enalapril and losartan. These
      differences could have a therapeutic relevance.

PMID- 10962892
TI  - [The importance of folic acid in current medicine].
AB  - Lately, folic acid deficiency is gaining a predominant role in the pathogenesis
      of congenital malformations and cardiovascular diseases in adults. The planning
      of individual and population preventive strategies for these diseases must
      consider this deficiency. This paper reviews the anatomical, biochemical and
      molecular bases of neural tube defects and cardiovascular diseases in adults. In
      these two frequent diseases, folic acid supplementation has shown a clear cut
      protective effect.

PMID- 10962893
TI  - [Severe exposure to environmental lead in a child population in Antofagasta,
      Chile].
AB  - BACKGROUND: In Antofagasta, Chile, lead is gathered in bulk in urban zones,
      contaminating surrounding schools and houses. AIM: To verify if the environmental
      lead exposure results in high blood lead levels in children living near lead
      storage sites. MATERIAL AND METHODS: Four hundred eighty-six children under 7
      years old, living near lead storage sites and 75 children living far away form
      these sites, were studied. An inquiry was applied and venous blood was drawn.
      Air, soil and water lead concentrations were also measured. RESULTS: Lead
      geometric mean concentrations in exposed children were 8.7 micrograms/dL and 4.22
      micrograms/dL in unexposed children. Forty seven percent of exposed children and
      no unexposed children had lead levels over 10 micrograms/dL. The distance of
      dwellings from lead storage sites, their geographic location and their antiquity
      were significantly associated with high blood lead levels. Multivariate models
      disclosed that people living in contaminated sites have an odds ratio of 24.9 for
      high blood lead levels. CONCLUSIONS: Environmental lead contamination is
      significantly associated with high blood lead levels.

PMID- 10962894
TI  - [Characterization of the non coding 5' region of hepatitis C virus].

PMID- 10962895
TI  - [Bacteriology of gallbladder bile].

PMID- 10962896
TI  - [Principles of evidence-based medicine in the surgical treatment of colorectal
      cancers].
AB  - The principles of evidence-based medicine (EBM) are summarized. The surgical
      activity of the author's team is analysed to answer the question of whether the
      principles of EBM prevail in their surgical treatment of colorectal cancer.
      Results of some comparative studies are presented as concerns preoperative
      preparation, antibiotic prophylaxis, and the development of the suture technique
      applied. The changes of radicality in the surgery of colorectal cancer are
      discussed. It is emphasized that three newly developed procedures are routinely
      used in their practice to enhance surgical radicality and to improve the 5-year
      survival rate: 1. subtotal colectomy for obstructive left side colonic tumours,
      2. total mesorectal excision for middle and lower third rectal cancer, and 3.
      multivisceral resections for the treatment of advanced colorectal tumours. The
      advantages of new methods recently introduced in Hungarian colorectal surgery are
      guaranteed by previous published studies. The team has made efforts to develop
      new methods and to control the results in routine surgery. Only the surgical
      practice during the past few years could be influenced by the principles of EBM,
      but even so the maintenance of surgical standards, the application of results of
      well-documented reliable studies and efforts to develop new and better methods
      reflect principles equivalent to those of EBM in colorectal surgery in the past
      two decades.

PMID- 10962897
TI  - [Change in the allergen spectrum of hay fever patients in the Southern  Great
      Plains of Hungary (1990-1998)].
AB  - On the basis of their 9-year-long allergological and aeropalinological studies
      the authors examined if the allergen spectrum of their hay fever patients in
      connection with the seasonality of the symptoms and the pollen count of these 9
      years has changed or not. The results of the skin prick tests and of the case
      histories of patients examined in 1990/91 and 1997/98 were compared. Pollen
      counting was performed with a Lanzoni VPPS 2000 sampler. By the end of the
      examined period the ratio of severely polysensitized patients (with 4 or more
      positive skin prick tests) increased significantly according to the significantly
      increased amount of positive skin prick tests to trees, rye and plantago. As the
      seasonality of the patients, symptoms did not change during this period, this
      increase in skin prick test positivity means a latent allergy. In a few years,
      however it may become a manifest allergy causing symptoms in early springtime.
      According to the pollen count results the atmospheric pollen pollution of the
      region was markedly high during the possible period of these patients'
      sensitisation.

PMID- 10962898
TI  - [Treatment of hyperprolactinemic anovulation with the dopamin-agonist
      quinagolide].
AB  - Quinagolide has a strong dopaminerg activity, suppresses prolactin secretion and
      restores gonadal function in women with hyperprolactinemic anovulation. The aim
      of our study was to investigate the effectiveness of quinagolide in the treatment
      of 16 hyperprolactinemic patients. The clinical diagnosis was functional
      hyperprolactinemia in 13 patients, microprolactinoma in 2 and empty sella
      syndrome in 1. The drug was administered orally and initially daily dose was
      0.025 mg for the first three days, 0.050 mg for the next three days and 0.075 mg
      for the following 6 months. The serum prolactin level was measured monthly before
      pregnancy, three monthly during the pregnancy and six weeks after delivery. Serum
      prolactin levels decreased in most of the patients during the first month and
      only in one case remained in the pathological range after six months
      quinagolide++ treatment. Prolactin secretion changed (mean and range) from 3120
      (780-5790) mU/l to 370 (84-1076) mU/l. Out of 16 hyperprolactinemic patients nine
      women were infertile. During quinagolide treatment 5 pregnancies occurred. In
      conclusion, our results show that quinagolide has a good efficacy on regulation
      of prolactin secretion and it is a well tolerated dopamin-agonist drug.

PMID- 10962899
TI  - [Forecasting the number of patients with end-stage renal disease (Model of the
      system)].
AB  - The authors are dealing with the renal replacement therapies in Hungary. They are
      on the opinion that in view fo patient flow renal replacement therapies (such as
      various methods of dialysis and kidney transplantation) can be considered as one
      system. With analysing the number of patients in the past years they can
      establish that end-stage renal disease puts significant burden on the health
      insurance fund. According to their calculations the number of patients with end
      stage renal disease will increase by 14-16% in the next few years if current
      trends continue. If we want to operate the system efficiently, we can reduce--up
      to a certain extent--the economic burden of dialysis by increasing the number of
      kidney transplantations.

PMID- 10962901
TI  - [Anomalies of scientometry in Hungary].

PMID- 10962900
TI  - [Recent recurrence of a Biblical case of complicated twin birth].
AB  - The authors present a case which appears to resemble the child-birth of Thamar
      described in the Bible. The arm of one of the sons of Thamar prolapsed during the
      process of delivery. The same complication occurred in a patient of the authors,
      involving laid a head the arm of a male fetus. In both instances, the other twin
      child was born first, in the case of Thamar by the vaginal route, in that of the
      authors, by cesarean section. The description of this birthing event in the Bible
      permits the conclusion that complication observed in contemporary obstetric
      practice already occurred 7000 years ago.

PMID- 10962902
TI  - [Oxidative stress and antioxidant defense in alcoholic liver disease and chronic
      hepatitis C].
AB  - In the past decade it became accepted that free radicals, lipid peroxidation and
      antioxidant defense play a role in various tissues damages, thus in certain liver
      diseases as well. Since only limited data have been reported concerning the
      oxidative stress in viral hepatitis, a comparative study was performed in
      patients (pts) with chronic hepatitis C and alcoholic liver disease. In addition,
      the effects of a flavonolignan drug silymarin were assessed. 10 pts with chronic
      hepatitis C, 5 pts with alcoholic hepatitis and 13 pts with alcoholic cirrhosis
      have been investigated. Biochemical liver tests (serum bilirubin,
      aminotransferases, ALT, AST, lactate dehydrogenase (LDH), pseudocholinesterase,
      prothrombin), malandialdehyde (MDA) levels in plasma and red blood cell (RBC)
      hemolysate, superoxide radical generating capacity of stimulated
      polymorphonuclear granulocytes (PMN), plasma concentrations of reduced (GSH) and
      oxidized (GSSG) glutathione, vitamin A, luteine and beta carotene, furthermore
      RBC superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase
      activities were determined. The level of plasma MDA--as the marker of lipid
      peroxidation--was highest in alcoholic cirrhosis (five times of normal) (p <
      0.05), the RBC hemolysate MDA was most elevated in chronic hepatitis C (p <
      0.05). The mean PMNs' superoxide radical generating capacity was 116.6% of normal
      control in alcoholic hepatitis, where the mean GSH level was the lowest (89.8% of
      normal). Plasma vitamin A content was lowest in alcoholic cirrhosis (68% of
      control) (p < 0.05). SOD activity was elevated in both chronic hepatitis C and
      alcoholic cirrhosis, where GPx activity was decreased (p < 0.05). There was a
      correlation between LDH and SOD activities (r = 0.77, p = 0.015). Silymarin
      treatment of one month duration resulted in normalization of serum bilirubin in
      55% of treated pts, AST became normal in 45%, and RBC hemolyzate MDA level
      normalized in similar rate. A significant increase in both GSH and retinoids was
      found. Alterations in oxidative stress and antioxidant defense system were shown
      in chronic hepatitis C, not only in alcoholic liver disease. The parameters of
      lipid peroxidation and antioxidant defense may be useful surrogate markers for
      monitoring pts with liver disease during hepatoprotective treatment.

PMID- 10962903
TI  - [Parvovirus B19 infection in hydrops fetalis].
AB  - In a retrospective study from 210 foetal autopsies carried out in a period
      between 1992 and 1999 fifteen hydropic foetuses were found. The cause of the
      hydrops was shown to be Rh incompatibility in one case only. The cause of hydrops
      was not discernible in one case. In the others pathological examination clarified
      the cause and pathomechanism of non-immune hydrops. One isolated cystic hygroma,
      one monochorionic twin pregnancy with twin to twin transfusion, one case of
      sacrococcygeal teratoma and 4 cases of congenital heart diseases were reported.
      Postmortem interphase cytogenetic examination showed X0 monosomy in 2 cases. In
      further 4 foetuses pathognomic viral inclusions in the proerythroblasts raised
      the probability of parvovirus B19 infection what was confirmed by
      immunohistochemistry and electronmicroscopic examination. The occurrence of the
      parvovirus B19 associated cases of foetal hydrops was shown to be higher (4/15)
      in this series than in the literature. The accumulation of cases in 1998 is
      suggestive of an outbreak. The prenatal diagnostic implications and the attempts
      on further management are also discussed.

PMID- 10962904
TI  - [Aberrations of chromosome 18 and their significance in genetic counseling].
AB  - In order to get information on the origin of chromosome 18 aberrations trisomy 18
      cases were analysed as well as different chromosome 18 rearrangements. In total,
      their study population consisted of 100 trisomy 18 patients and their parents, 67
      out of which have already been published. Additionally, seven families were
      analysed with structural aberrations of chromosome 18 including four patients
      with tetrasomy 18p. Determination of parent and cell stage of origin was
      performed by short tandem repeat typing (STR, microsatellites). These
      investigations revealed that the additional chromosomal material in the majority
      of the chromosomal 18 aberrations was maternal in origin (97/107). In most of the
      cases the nondisjunction occurred during maternal meiosis II. This was in
      agreement with findings of other groups. Thus, independently from the type of
      aberration, there was a predisposition of chromosome 18 for nondisjunction in
      maternal meiosis II. In this respect, chromosome 18 seemed to be unique among
      human autosomes. Furthermore, these results showed that molecular genetic
      analyses of chromosomal aberrations and their formation mechanisms were
      meaningful tools in genetic counselling situations: in 5 cases where cytogenetic
      investigations could not performed, the clinical diagnosis of Edwards syndrome
      could be confirmed by molecular findings. Thus, in these cases other genetic
      diseases with differing types of inheritance could be excluded from being the
      cause of the observed malformations. In a further structural rearrangement of
      chromosome 18, the origin could be determined as being mitotic, therefore a
      recurrence risk could be excluded for this couple.

PMID- 10962905
TI  - [Adult Hirschsprung's disease with mental retardation and microcephaly].
AB  - Hirschsprung's disease occurs rarely and sporadically in adult, involving males.
      In cases, which are manifested perinatally, the so called Hirschsprung-associated
      congenital anomalies (mainly central nervous system, urogenital and
      cardiovascular) may present (2-21%), which have not observed in adult. Mental
      retardation and Hirschsprung's disease more frequently are associated with Down
      syndrome (5-10%). The discoveries of molecular genetics in the last 4-5-years
      through the examination of transgenic ("knockout") mice, proved the basic role
      the mutation of 4 genes: the RET (receptor tyrosin kinase), a proto-oncogene,
      coding its ligand, the glial cell-line derived neutrophic factor (GDNF), the gene
      of the endothelin-B receptor (ENDRB) and the gene one of its ligand, the
      endothelin-3 (EDN3), in the pathogenesis of Hirschsprung's disease. In our case,
      the short segment Hirschsprung's disease caused respiratory and cardiac failure,
      which was recognized by autopsy. Besides, the severe mental retardation, the role
      of the long term use of antipsychotic medicines comes up in the prolongation and
      masking of the symptoms. The accompanied mental retardation and microcephalia in
      early childhood are known, which are associated anomalies with Hirschsprung's
      disease. In cases of Hirschsprung diseases at adults, no other associated
      congenital anomalies has been published. The mental retardation in Down-syndrome,
      in association with Hirschsprung's disease (and presumable in our case, too) is
      supposed to be the consequence of the mutation in the gene of GDNF. In this case,
      we observed, that the so called short segment H-d was accompanied at a 33 years
      old men patient with mental retardation (who was originated from a gypsy ethnic
      minority), because of it the connection of the nurses and the patient was
      disturbed and the main symptom of the H-d (chronic obstipation) remained hidden.
      The mechanic ileus was going on behind the scenes, and in addition to the cardiac
      failure caused the death of the patient. Practical conclusion of the case is
      that, Hirschsprung's disease should be suspected in all adult patients, who had
      severe obstipation persisting since childhood, especially in males.

PMID- 10962906
TI  - [Skerlievo disease: a large syphilis outbreak two hundred years ago].

PMID- 10962907
TI  - ["Tricky" Latin verbs, nouns, adjectives].

PMID- 10962909
TI  - [The inflammatory rheumatic diseases. A discipline in action].

PMID- 10962910
TI  - [Smoking in health care. Is it advancing?].

PMID- 10962908
TI  - [In memory of professor Geza Hetenyi].

PMID- 10962911
TI  - [Treatment of diabetic patients with ischaemic heart disease].
AB  - Patients with diabetes constitute a large group among patients with ischaemic
      heart disease, and their risk of repeated cardiovascular events is large. Due to
      this, there is increasing focus on intervention against the increased risk of
      cardiac morbidity and mortality in patients with diabetes. Subgroup analyses of
      patients with diabetes from studies on patients with ischaemic heart disease show
      that intervention with thrombolysis, aspirin, beta blockers, ACE inhibitors and
      statins have similar relative benefit among patients with diabetes, but because
      of the greater risk in these patients, the absolute benefit is increased. In
      spite of this, intervention is less common among patients with diabetes, a fact
      that should be corrected. Direct intervention targeted at the metabolic disorder
      in ischaemic heart disease has only been investigated in the DIGAMI study, where
      glucose/insulin treatment followed by long term treatment with insulin was
      compared to conventional treatment. The mortality was lower in the insulin
      treated group after one to four years of follow up, a promising result which is
      currently being investigated in the DIGAMI-2 study.

PMID- 10962912
TI  - [Genetic mapping in relation to disease susceptibility].
AB  - The search for chromosome regions that potentially harbour susceptibility genes
      for diseases by investigating the inheritance of disease and DNA markers in
      groups of patients is the initial step in the identification of the specific
      genes involved. The identification of genes involved in disease susceptibility is
      one of the main research strategies for unravelling the etiology and
      pathophysiology of many common diseases. However, such diseases often have a
      complex etiology which makes the genetic mapping of the involved disease genes
      very difficult. Fortunately, a number of different methods exist for genetic
      mapping of disease genes.

PMID- 10962913
TI  - [Diagnosis of common bile duct stones in symptomatic gallstone disease].
AB  - It is unclear which diagnostic procedure is optimal for the detection of common
      bile duct stones prior to laparoscopic cholecystectomy. It is routine to use
      blood tests for liver function and transabdominal ultrasound, and the best method
      is currently to continue evaluation with other methods when one or more blood
      tests for liver function are elevated and/or the diameter of the common bile duct
      is > or = 10 mm on transabdominal ultrasound. Magnetic resonance cholangiography,
      endoscopic ultrasound, laparoscopic ultrasound, intraoperative cholangiography
      and endoscopic retrograde cholangiography are all accurate in the detection of
      common bile duct stones. Intravenous cholangiography and computer tomography
      needs further evaluation before final recommendations can be made. Intraoperative
      cholangiography and endoscopic retrograde cholangiography have the best
      documentation available in the literature. Intraoperative cholangiography is
      easy, cheap and without significant complications, whereas endoscopic retrograde
      cholangiography has a high morbidity and mortality rate. Endoscopic retrograde
      cholangiography is therefore not suitable as a diagnostic test and should be
      abandoned as such in the future. Patients with cholangitis, jaundice and common
      bile duct stones visualised by transabdominal ultrasound have a high risk of
      common bile duct stones, and these patients can therefore undergo endoscopic
      retrograde cholangiography directly. Other patients should have a magnetic
      resonance cholangiography or endoscopic ultrasound preoperatively, or
      intraoperative cholangiography or laparoscopic ultrasound depending on local
      factors such as available equipment and surgical expertise.

PMID- 10962914
TI  - [Smoking habits and attitude toward tobacco use among health professionals in
      Denmark in 1996].
AB  - The purpose of the study was to investigate smoking habits in different groups of
      health professionals. A total of 7844 were interviewed using postally distributed
      questionnaires. The response rate was 85%. The study showed a much lower smoking
      prevalence among groups of health professionals compared to the normal population
      apart from social assistants and hospital porters, where the smoking rate was
      even higher than in the Danish population. Among medical doctors, dentists,
      nurses and midwives the smoking rate had decreased faster from earlier
      investigations than among the Danish population. Future strategy in Danish policy
      concerning campaigns in the population and among health professionals as role
      models is discussed. Fifty-two percent of the interviewed agreed that health
      professionals should not smoke, while on duty, but with quite big differences
      between the groups (min. 31% among hospital porters, max. 73% among dentists).

PMID- 10962915
TI  - [Magnetic resonance imaging as a marker of inflammation, destruction and
      prognosis in rheumatoid arthritis wrists].
AB  - To evaluate MRI for assessment of inflammation, destruction and prognosis in
      rheumatoid arthritis (RA), 26 RA patients, randomized to disease-modifying anti
      rheumatic drug (DMARD) therapy alone or in combination with oral prednisolone,
      were followed for one year with contrast-enhanced MRI of the dominant wrist
      (months zero, three, six and 12), conventional radiography and clinical and
      biochemical examinations. Significant synovial membrane volume reductions were
      observed in both groups, earliest in the DMARD + prednisolone group. The rate of
      erosive progression on MRI was highly correlated with baseline and area-under
      curve (AUC)-values of synovial membrane volume, but not with baseline or AUC
      values of local or global clinical or biochemical parameters, nor with +/-
      prednisolone. MRI was more sensitive than radiography as regards detection of
      progressive bone destruction (22 versus 12 new bone erosions). MRI may prove
      valuable as marker of joint disease activity and destruction and, perhaps,
      prognosis in RA.

PMID- 10962916
TI  - [Intrathoracic lipoma].
AB  - A case of intrathoracic lipoma is presented. The radiographic signs of fatty
      tumours of the thorax are nonspecific. CT is helpful in the diagnosis and follow
      up of this rare benign tumour. CT shows the exact location of the tumour and its
      characteristics. An attenuation coefficient of -140 to -70 HU is characteristic
      for the tumour and, if the tumor is asymptomatic, conservative management with
      careful follow-up is justified.

PMID- 10962917
TI  - [Application of an implantable ECG monitoring recorder in recurrent syncopes].
AB  - The usefulness of a new diagnostic tool is reported in a case of recurrent
      syncopes of unknown origin. A subcutaneous monitoring device for long-term
      continuous ECG recording was implanted in a patient with very infrequent
      recurrent syncopes, and after seven months the syncope recurred. Retrieving ECG
      data showed an abrupt bradycardia episode with a total duration of 13 second and
      a 7.5 second episode of asystole. A DDDR pacemaker was implanted and at the same
      time the Loop Recorder was explanted. A suggestion for an algorithm for
      evaluation of unexplained syncope is presented.

PMID- 10962919
TI  - [Fatal intracerebral hemorrhage after amphetamine intake].
AB  - A fatal case of massive intracerebral hemorrhage in a 20-year-old woman after
      first-time amphetamine abuse is described along with a review of the literature.

PMID- 10962918
TI  - [Borreliosis associated with Lofgren's syndrome].
AB  - A man with positive Borrelia-titres, joint pain, erythema nodosum and fever was
      treated with penicillin. After finding hilar adenitis Lofgren's syndrome was
      thought to be more likely and penicillin was discontinued. Later the patient
      developed symptoms of neuroborreliosis and S-Borrelia IgG was 10 units. After
      treatment with doxycycline symptoms disappeared and IgG levels fell.

PMID- 10962920
TI  - [Picture of the month. Splenomegaly with hereditary stomatocytosis].

PMID- 10962921
TI  - [Are the drugs of colonoscopy gone--follow up after polypectomy?].

PMID- 10962922
TI  - [Primary prophylactic treatment with implantable defibrillator in high risk
      patients].

PMID- 10962924
TI  - [The basic research fund in Denmark].

PMID- 10962923
TI  - [Ecstasy].

PMID- 10962925
TI  - [Good reasons for mammography screening. About misunderstood criticism of
      underlying investigations!].

PMID- 10962926
TI  - [Microdeletion of 22q11, DiGeorge and velocardiofacial syndrome].

PMID- 10962928
TI  - [In Process Citation]

PMID- 10962927
TI  - [Somatization problems].

PMID- 10962929
TI  - [Randomization is not only a word].

PMID- 10962930
TI  - [A wandering gastrostomy tube].

PMID- 10962932
TI  - [Screening of lung cancer].

PMID- 10962931
TI  - [The placebo concept--a comment].

PMID- 10962933
TI  - [Atovaquone/proguanil. Prophylaxis and treatment of malaria].
AB  - Malarone is a combination of the two drugs atovaquone and proguanil. Malarone is
      useful as prophylaxis and for the treatment of falciparum malaria. Monotherapy
      using atovaquone or proguanil results in treatment failure in 30% and 90%
      respectively, whereas treatment failure is rare when a combination of the drugs
      is used (< 2%). This reflects the synergistic effect of this drug combination.
      Used as a chemoprophylaticum against falciparum malaria Malarone has an effect of
      > 95%. The protective mechanism is likely to act via the mitochondrial cytochrome
      bc complex, thus a different mechanism from other malaria drugs. For this reason,
      cross-resistance with other malaria drugs is not expected. The documentation of
      effect and safety profile of Malarone in malaria prophylaxis makes it a suitable
      alternative to mefloquine and doxycycline in case of contraindications. Malarone
      is effective for the treatment of acute uncomplicated malaria, and may be used as
      an alternative to mefloquine.

PMID- 10962934
TI  - [Raloxifene].
AB  - Raloxifene belongs to the group of selective estrogen receptor modulators
      (SERMs). It interacts with both estrogen receptor alpha and beta, but the
      postreceptor responses differ from those of estrogens. Raloxifene exerts tissue
      specific responses that differ from estrogens. The drug increases bone mass by 2
      3% and inhibits the risk of subsequent vertebral fractures by 30-50%. Raloxifene
      reduces the risk of breast cancer by 76% after treatment for four years and
      builds an atrophic endometrium without any bleedings. Furthermore, the risk of
      endometrial cancer is not increased. The drug exerts positive effects on plasma
      lipids, but the effects of these changes on subsequent risk of myocardial
      infarction and cardiovascular death are still unknown. The main side effects are
      leg cramps, increases in hot flushes and peripheral oedema. Like estrogen, the
      drug increases the relative risk for venous thrombosis by a factor three.

PMID- 10962935
TI  - [Parasitologic diagnostics].

PMID- 10962936
TI  - [Impotence as adverse effect].

PMID- 10962937
TI  - [Audit--a method of quality assurance of clinical practice].

PMID- 10962938
TI  - [Bone marrow examination].

PMID- 10962939
TI  - [Forensic medicine epidemiology].

PMID- 10962940
TI  - [Treatment of common bile duct stones].
AB  - Open single-stage treatment of gallstones and common bile duct stones (CBDS) has
      previously been standard procedure. Endoscopic stone extraction after a
      sphincterotomy has become a well-established therapeutic modality during the last
      twenty years and is now the standard procedure. The available options for
      management of patients with CBDS are reviewed. Although there is no evidence
      concerning the best treatment of CBDS, it is concluded, that a two-stage
      procedure with endoscopic CBDS extraction followed by cholecystectomy has no
      advantages over a single stage open or laparoscopic procedure. In the future the
      treatment of CBDS will be differentiated depending on size of the stone, the
      occurrence of complications to CBDS and the general health of the patient.

PMID- 10962941
TI  - [Menetrier's disease. Another Helicobacter pylori associated disease?].
AB  - Menetrier's disease is a rare and poorly outlined disease, diagnosed in patients
      with giant gastric folds, dyspeptic symptoms and hypoalbuminaemia due to
      gastrointestinal protein loss. The etiology is unknown, but Menetrier's disease
      is often associated with Helicobacter pylori (Hp) infection. Case reports and
      studies concerning the effect of eradication therapy in patients with Menetrier's
      disease were reviewed. It was found that complete normalisation of the gastric
      mucosa and gastrointestinal protein loss following eradication therapy has been
      reported in several cases. In conclusion, we recommend patients with Menetrier's
      disease to be tested for Hp, and treated with eradication therapy in case of
      infection.

PMID- 10962943
TI  - [Infertility in ethnic groups. Etiology and treatment].
AB  - In this retrospective case control study we analysed the causes and treatments of
      infertility in 100 ethnic couples consecutively discharged from the Fertility
      Clinic in the period October 1995 to March 1999. The mean age at referral was 28
      years (19-37) for ethnic women and 31 years (24-39) for Danish women. Male
      infertility was the most frequent cause in ethnic couples compared to Danish
      couples (24% vs. 16%; NS). Tubal infertility was less frequent in ethnic than in
      Danish couples (19% vs. 45%; p < 0.01), ovulatory defects were more frequent in
      ethnic couples than in Danish (13% vs. 4%; p < 0.04). Among ethnic couples 57
      (118 cycles) underwent IVF and ICSI treatment vs. 85 (198 cycles) Danish couples
      (p < 0.01). The ongoing pregnancy rate per initiated cycle was 29.6% in ethnic
      couples vs. 24.2% in Danish couples (NS). Forty four percent of the ethnic
      couples did not complete the whole treatment program vs. 29% of Danish couples (p
      < 0.04). This may be due to cultural differences and difficult communication.

PMID- 10962942
TI  - [Elderly people admitted to hospital for social reasons. Patients' and their
      networks' perceptions of problems and expectations prior to the admission].
AB  - Elderly people may be admitted to hospital for social reasons. The aim of this
      study was to describe problems that lead to the admission and the expectations of
      the elderly and their network. Thirty-nine qualitative interviews were made with
      39 informants. Data were analysed according to Grounded Theory. The backgrounds
      for the admissions were a mixture of social, psychological and physical reasons.
      The elderly found themselves isolated, lonely and sometimes afraid. They had no
      expectations of treatment. The network hoped that the admission would mean
      changes at home and in primary healthcare. Admissions due to social reasons
      should be avoided, but were necessary as there were no other solutions.
      Suggestions are presented.

PMID- 10962944
TI  - [Hygiene in general practice].
AB  - The purpose of this study was to examine how general practitioners handle
      infection control precautions. The study is based on interviews with 26 general
      practitioners. The following subjects were included: hand washing, skin
      disinfection of the patients before injections and minor surgery and disinfection
      and sterilisation procedures of the instruments. The investigation demonstrated
      that the precautions varied widely. A manual describing simple and safe infection
      control precautions in the outpatient setting has been written.

PMID- 10962945
TI  - [Influence of fetal weight on outcome of prolonged pregnancy].
AB  - The aim of the study was to compare the influence of foetal weight on the outcome
      of a prolonged pregnancy. The study group consisted of all women delivered after
      a prolonged pregnancy at the Dept. of Obstetrics, Herning Central Hospital,
      during the period from 1.1.1993 to 31.3.1999, stratified by foetal weight. Five
      hundred and eighty women were included. Women who gave birth to a child with
      birthweight less than 3.5 kg were more frequently given oxytocin infusions, and
      more children were transferred to the neonatal care unit. Heavy children weighing
      at least 4.5 kg were more frequently delivered by Cesarean section. In all groups
      very few children had low Apgar scores. When comparing the study population to a
      population of women giving birth after a completely normal pregnancy,
      significantly more grade 3-4 perineal ruptures and intrumental deliveries were
      found in the study group. In conclusion, foetal weight seems to be a poor
      predictor of the outcome after prolonged pregnancy. Prolonged pregnancy is
      associated with more instrumental deliveries and perineal ruptures.

PMID- 10962946
TI  - [Emergency contacts with a gynecologic department. Therapeutic and examination
      requirements].
AB  - Emergency room contacts serviced by the Dept. of Gynaecology at Copenhagen County
      Hospital, Glostrup, are increasing in number. During a 12-week period we
      conducted a prospective survey of these contacts using a structured
      questionnaire. Subsequently and based on case sheets a specialist evaluated the
      relevance of each contact. We found that nine out of ten contacts presented
      problems relevant to gynaecology; of these one half presented problems in early
      pregnancy. In 81.7% of all contacts it was found that care could safely have been
      postponed to daytime hours. Compared to daytime activity the emergency room
      patient experienced a longer waiting and treatment time, and patients were more
      often cared for by a junior gynaecological physician without supervision. We
      concluded that a majority of emergency room calls serviced by our gynaecological
      department could safely be referred to daytime hours with advantages for both
      patients and physicians in training.

PMID- 10962947
TI  - [Symptomatic pseudolithiasis caused by Rocephalin].
AB  - Treatment with ceftriaxone may be accompanied by precipitation of ceftriaxone
      calcium salts in the gallbladder, called pseudolithiasis. We present a case, in
      which a formerly healthy five year-old girl developed symptomatic pseudolithiasis
      during treatment with Rocephalin. The symptoms and pseudolithiasis disappeared
      after a few days with symptomatic treatment and change of antibiotics.

PMID- 10962948
TI  - [Villous adenoma of the rectum with electrolyte imbalance. McKittrick-Wheelock
      syndrome].
AB  - We present a case of villous adenoma of the rectum, associated with severe fluid
      imbalance in a 69 year-old, previously healthy woman. Severe dehydration with
      hyponatraemia, hypokalaemia, acidosis/alkalosis and watery diarrhoea is typical.
      Clinical presentation may include fatigue, confusion, convulsions or coma.
      Intensive rehydration is the primary intervention, and causal treatment is always
      surgery. Normally full recovery is achieved.

PMID- 10962949
TI  - [Prevention and treatment of osteoporosis--have we come any further? A cross
      sectional study of hospitalized patients].

PMID- 10962950
TI  - [Are PPAR-gamma-agonists a secure choice in treatment of overweight diabetic
      patients?].

PMID- 10962951
TI  - [In Process Citation]

PMID- 10962952
TI  - [Screening for lung cancer].

PMID- 10962953
TI  - [Paracetamol. New knowledge about pharmaceutical action, analgesic relief and
      anti-inflammatory effects compared with non-steroidal anti-inflammatory effect].
AB  - Paracetamol is usually termed a peripheral analgesic from the common belief that
      its site of action is near the injury. In this review a possible central action
      is summarised. Furthermore the analgesic effect of paracetamol is compared to non
      steroidal anti-inflammatory drugs and the possible anti-inflammatory effect of
      paracetamol is discussed.

PMID- 10962954
TI  - [The GCP-unit at the Aaarhus University Hospital].

PMID- 10962955
TI  - [Evidence-based dermatology and medicine].

PMID- 10962956
TI  - [The statistical case reports].

PMID- 10962957
TI  - [Dyslipidemia, diabetes and cardiovascular disease].

PMID- 10962958
TI  - [Preimplantation diagnosis of dominant inherited diseases with late debut].

PMID- 10962959
TI  - [Treatment of upper respiratory tract infections].
AB  - Today most upper respiratory tract infections are mild and of short duration with
      minor risk of complications. Hence, the effects of antibiotic treatment are
      marginal. The only and most important reason for treatment is to stop
      dissemination. Penicillin V should be the first drug of choice. A review of the
      literature about antibiotic treatment of upper respiratory tract infections shows
      that most published studies exclude two categories of patients: children below
      the age of 6 months and patients who are severely ill. Therefore, there is an
      additional need for further studies focused on select groups of patients to
      investigate the benefit, if any, of antibiotic treatment as well as to study the
      effect of introducing near-patient-tests and the use of extended microbiological
      service in daily clinical practice.

PMID- 10962960
TI  - [Dendritic cells--and their possible applications in cancer therapy].
AB  - Dendritic cells (DCs) represent a group of antigen-presenting leukocytes which
      are very effective in activating resting T-cells. DCs are present in almost all
      tissues of the body, but they are generally difficult to isolate. The study of
      human DCs has recently become greatly facilitated due to the advent of methods
      for isolation and in vivo generation of DCs from blood. Experiments in animal
      models have shown that DCs loaded with tumour antigens may induce effective
      immune responses against cancer. Now the potential of vaccination with tumour
      antigens presented on DCs is being evaluated in cancer patients. Preliminary
      clinical studies have shown encouraging results.

PMID- 10962961
TI  - [Evidence-based ambulatory dermatological treatment].
AB  - The evidence base for routine therapeutic decisions in dermatological out
      patients was studied in a random sample of the case-notes from 115 out-patients.
      The evidence base of therapy prescribed when the diagnosis was ascertained was
      studied in literature searches in MEDLINE and EMBASE. Evidence was structured
      into primary evidence consisting of randomised controlled trials, and secondary
      evidence consisting of follow-up studies or applying trial results from clinical
      analogies, e.g. atopic and seborrheic dermatitis treatment. Randomised controlled
      trials could be found describing 38% (95% confidence interval: 30-47) of all
      treatments. Secondary evidence was found for 33% (24-41), while no evidence was
      found for 23% (16-31) of the given treatments. Approximately 75% of
      dermatological out-patient therapy is founded on scientific evidence spanning
      from randomised controlled trials to logical deduction about a given disease from
      an analogous clinical situation. The proportion of evidence based medicine in
      dermatological therapy therefore appears comparable to that of other fields of
      medicine.

PMID- 10962962
TI  - [Prevalence and incidence of dementia in Denmark. The Odense study].
AB  - Prevalence and incidence of dementia were determined for 65-84 year-old persons
      living in the municipality of Odense and randomly drawn from the Danish Civil
      Registration System (DCRS). All participants were examined with CAMCOG, the
      cognitive section of CAMDEX (The Cambridge Examination for Mental Disorders of
      the Elderly) and the follow-up period was two years. Individualized CAMCOG cut
      off scores were determined by multiple linear regression. Possibly demented
      persons were further examined with the remaining part of CAMDEX and
      neuropsychological tests. Alzheimer's disease (AD) was diagnosed according to the
      NINCDS-ADRDA criteria for probable AD, and vascular dementia (VD) and dementias
      of other types according to the DSM-III-R criteria for dementia. The severity of
      dementia was determined according to the Clinical Dementia Rating scale. Of the
      5,237 persons drawn from the DCRS, 3,346 participated in the prevalence study and
      2,452 in the incidence study. The prevalence was 7.1% (66.7% AD, 18.3% VD, and
      15.0% dementias of other types). Ninety-six (2.8%) were diagnosed as very mildly
      demented. The incidence rate was 29.5 new cases per 1,000 person-years and 20.9
      for AD. Inclusion of cases with very mild dementia resulted in higher prevalence
      and incidence rates than generally reported.

PMID- 10962963
TI  - [Neutralization of lidocaine-adrenaline. A simple method for less painful
      application of local anesthesia].
AB  - The amount of sodium bicarbonate necessary to neutralise commercially available
      lignocaine-epinephrine (pH 4.7) to physiologically neutral pH (7.4) was
      established. The analysis showed that neutral pH could be accomplished by adding
      1.0 ml sodium bicarbonate (8.4 g/l) to 10 ml lignocaine-epinephrine (1%, 5
      microgram/ml). Chemical analysis also established that the neutralised lignocaine
      epinephrine was stable for 24 hours after adding sodium bicarbonate. A double
      blinded randomised clinical trial with crossover design done on volunteers from
      hospital staff proved that injection of neutralised lignocaine-epinephrine is
      less painful than commercially available lignocaine-epinephrine (p < 0.001).

PMID- 10962964
TI  - [Quality development at a medical department].
AB  - Organization on medical wards have an impact on patient continuity, both
      regarding contact with physicians and nurses. Highest continuity was found in
      teams with approximately 20 beds. Members ought to spend most of their time in
      the team. This was found to be especially important for the internal medical
      specialists. The amount of blood samples taken was lowest in the team with the
      highest patient-specialist continuity. Teams with or without continuity had the
      same high level of patient satisfaction.

PMID- 10962965
TI  - [Association or agreement between clinical measurement methods?].
AB  - Method comparison is often needed and unfortunately often analysed
      inappropriately. In particular, the use of correlation may be misleading with a
      high value of the correlation coefficient interpreted as an indication of good
      agreement. The difference between association and agreement are emphasized and
      the difference plot method is demonstrated using a worked example. Finally the
      interpretation of bias and limits of agreement are discussed.

PMID- 10962966
TI  - [Severe neonatal hyperparathyroidism in a family with familial hypocalciuric
      hypercalcemia].
AB  - Familial hypocalciuric hypocalcaemia (FHH) is a rare disorder, inherited in an
      autosomal dominant manner. It has earlier been believed that neonatal severe
      hyperparathyroidism (NSHPT) is the homozygous form of FHH, but in this case story
      we show that it is not always like that. We describe a girl who presents with a
      calcium metabolic disorder from birth. Genetic examination of the girl and her
      family shows a single abnormal allele in the calcium ion sensitive receptor. We
      discuss why some heterozygotic inactivating calcium receptor mutations cause
      NSHPT, while the majority of other mutations only cause mild, asymptomatic
      hypercalcaemia as in FHH.

PMID- 10962967
TI  - [Transurethral treatment of seminal vesicle abscess].
AB  - An 83-year old male with a seminal vesicle abscess is presented. Initially,
      cancer of the prostate was suspected and the findings of the transrectal
      ultrasound scan were misinterpreted. The diagnosis was made by CT-scan. When
      drainage failed the patient was treated successfully with transurethral
      unroofing.

PMID- 10962968
TI  - [Picture of the month. Ankylosing spondylitis].

PMID- 10962969
TI  - [Health in focus].

PMID- 10962970
TI  - [Carotid surgery in patients 80 years old or older].
AB  - BACKGROUND AND OBJECTIVE: Because of their high age and markedly increased co
      morbidity, physicians and geriatricians are often cautious in their indications
      for carotid thromboendarterectomy (TEA) in patients 80 years or older. However,
      it is these very patients who are subject to an exponentially increased risk of
      ischaemic cerebral vascular accidents (CVA). This study examined the morbidity
      and mortality rates of TEA in patients of this age group at one institution.
      PATIENTS AND METHODS: Between 1994 and 1998, among a total of 912 TEAs, 46 had
      been performed in patients 80 years or older (15 women, 31 men): indications,
      diagnosis and associated diseases as well as perioperative complications were
      entered prospectively into a data-bank. RESULTS: Only one patient (2.2%)
      sustained a perioperative CVA and no patient died. Three patients (6.5%)
      developed transitory neurological deficits. One patient had to have an emergency
      reoperation because of a postoperative carotid artery thrombosis. One patient had
      an intraoperative asystole due to a hypersensitive carotid sinus. There were no
      other serious cardiovascular or pulmonary complications. One patient sustained
      some oral muscle weakness as a result of intraoperative retractor pull on a
      branch of the facial muscle. CONCLUSION: These results indicate that even in
      patients of this age group carotid TEA can be performed with great safety.

PMID- 10962971
TI  - [Evaluation of the appropriateness of hospital care in internal medicine.
      Reliability of a German adaptation of the procedure].
AB  - BACKGROUND AND OBJECTIVE: The evaluation of the appropriateness of hospital
      admissions and hospital stays has become an increasingly important issue in
      Germany. Evaluations by the German Physicians Review Organizations (MDS, MDK)
      demonstrated the need for a standardized, valid and reliable assessment tool for
      inappropriate hospital use. Objective of this study was to test the reliability
      of a German adaptation of the "Appropriateness Evaluation Protocol" (AEP).
      PATIENTS AND METHODS: From the 2317 admissions to medical wards of a teaching
      hospital in Hessia in 1997 we randomly selected 52 patients to test the inter
      rater-reliability (54% female, mean age = 66 years +/- 18). Another 49 patients
      were randomly selected to test the intra-rater-reliability of the AEP (53%
      female, mean age = 61 years +/- 20). We estimated general agreement, specific
      agreement and Kappa statistics for the agreement of the evaluation of hospital
      admissions and hospital days. 95% confidence intervals were reported. RESULTS:
      The German adaptation of the AEP showed an inter-rater-agreement of 92% (88-96%)
      for hospital admissions and 76% (73-80%) for hospital days. Correspondingly, we
      observed an intra-rater-agreement of 96% (88-100%) for hospital admissions and
      93% (91-95%) for hospital days. The high agreement was independent of the length
      of hospital stay and independent of the proportion of inappropriate hospital
      days. CONCLUSION: A standard instrument for the assessment of the appropriateness
      of hospital care with known metric properties may be useful for quality
      management in hospitals and provide competitive advantages in a consolidating
      health care market. The AEP could be such an instrument.

PMID- 10962972
TI  - [Explanation of an unclear neurological syndrome by toxicologic investigation].
AB  - HISTORY AND CLINICAL FINDINGS: A 51-year-old man without relevant previous
      illness developed vomiting and diarrhoea, later also tingling and hypaesthesias
      in the limbs, as well as optical hallucinations that had occurred after a mid-day
      meal and drinking red wine. Neurological examination revealed variable pupillary
      reactions with anisocoria that would change from one side to the other. There was
      no paresis, muscle reflexes were brisk, more so on the right. Babinski reflex was
      positive on the right, there was an unsustained clonus of the right foot and the
      coordination tests were normal. Distal symmetrical hypaesthesias and
      paraesthesias were present in all limbs. An exogenous psychosis with restlessness
      and optical hallucinations was observed. INVESTIGATIONS: Routine blood count
      revealed leukocytosis. Serum concentrations of cGt and GPT were raised. Cerebral
      computed tomography and cerebrospinal fluid as well as microbiological tests of
      the mid-day meal were normal. DIAGNOSIS, TREATMENT AND COURSE: As the cause of
      the symptoms was initially unclear the patient was admitted to hospital and
      monitored without any specific treatment. Within one night all symptoms had
      disappeared and he was discharged the next morning without any complaints. Later
      the red wine which he had drunk was examined toxicologically and found to contain
      the "designer drug" DOB (2,5-dimethoxy-4-bromamphetamine). CONCLUSION: Accidental
      poisoning with DOB is probably a rare event which can hardly be included in
      routine differential diagnosis. If an acute cerebral organic syndrome has been
      excluded, only toxicological investigation can help in establishing the diagnosis
      in such cases.

PMID- 10962973
TI  - [Eosinophilia and polyneuropathy after percutaneous transluminal coronary
      angioplasty].
AB  - HISTORY AND CLINICAL FINDINGS: A 76-year-old man was admitted for a coronary
      angiography because of a postinfarction angina. Clinical examination was normal
      except a grade 2/6 systolic murmur and a slightly impaired vibration sense.
      INVESTIGATIONS: A slight anaemia, a slightly impaired renal function, and a
      slightly elevated cholesterol level could be found. The ECG showed a chronic
      anterior myocardial infarction. In the coronary angiography a double vessel
      disease was seen. TREATMENT AND COURSE: A percutaneous transluminal coronary
      angioplasty of the left anterior descending artery was performed and four stents
      were implanted. During the procedure a rush occurred in both legs following an
      appearance of livedo reticularis. Renal function deteriorated and there was an
      markedly increased number of eosinophils. With a new neurological check a marked
      peripheral neuropathy could be found. A biopsy of the sural nerve showed a
      necrotizing granulomatous inflammation of the nerve and the surrounding small
      arteries. Several small arteries contained needle shaped crystal clefts in their
      walls. The appearances were of multiple cholesterol emboli. Besides treatment of
      pain an immunosuppressive therapy with prednisone (100 mg/d) and cyclophosphamide
      (50 mg/d) showed no improvement. The patient died 2 months after the diagnosis of
      cholesterol emboli. CONCLUSION: Typically, cholesterol embolism occurs in elderly
      men within the eight weeks after arterial procedure. Diagnosis can be made only
      by histological examination. Cholesterol emboli syndrome may mimic systemic
      vasculitis. Therapy trial of cholesterol emboli syndrome usually fails and
      mortality rate is high.

PMID- 10962974
TI  - [Approximately annual periodicity of Helicobacter pylori prevalence].

PMID- 10962975
TI  - [Cholesterol embolism syndrome--a diagnostic challenge and a therapeutic
      dilemma].

PMID- 10962976
TI  - [Aerogenic enzymes are aggressive occupational inhalation allergens].

PMID- 10962977
TI  - ["Suicide" or "improvement" of the race. Contraception and medical practice in
      the introduction of ovulation inhibitors].

PMID- 10962978
TI  - [Learning from clinical cardiologic investigations].

PMID- 10962979
TI  - [Calculation of odds ratio].

PMID- 10962980
TI  - [Ultrasonographic examination of peripheral lung areas].

PMID- 10962981
TI  - [Biological signals for radiologic research].

PMID- 10962982
TI  - [Minimally invasive therapy options in aortic dissections].
AB  - Current day therapy for aortic dissection is aimed at the relief of branch vessel
      ischemia and the prevention of aortic rupture or aneurysm formation. Malperfusion
      complicating aortic dissection has historically been treated by surgery.
      Operations in patients with branch-vessel involvement may be technically
      difficult and the operative mortality is reported to be between 25% and 51%. This
      may rise to above 70% in patients with critical mesenteric or renal ischemia.
      Over the past decade, successful relief of such ischemia using the interventional
      radiological techniques of balloon fenestration, stent implantation and/or
      thrombolysis has been reported. In addition to being less invasive, this approach
      is associated with a lower mortality, ranging between 0% and 25%. Patency of the
      false lumen increases the probability of aortic rupture or aneurysm formation.
      Recent studies have reported successful closure of the proximal entry site with
      the help of stent grafts. The aim of the intervention is to initiate a thrombosis
      of the false lumen and thus stabilize the dissection. Based on a review of the
      literature and our own experience, we discuss the percutaneous management of
      branch vessel ischemia complicating aortic dissection as well as the role of
      stent graft implantation in patients with aortic dissection.

PMID- 10962984
TI  - [MR morphology of primary aneurysmal bone cysts: a retrospective analysis of 38
      cases].
AB  - PURPOSE: To define MR imaging characteristics of primary aneurysmal bone cyst.
      MATERIALS AND METHODS: MR imaging studies of 38 patients with histologically
      proven primary aneurysmal bone cyst were reviewed with reference to morphological
      features, signal characteristics, and patterns of contrast-enhancement. RESULT:
      Most lesions were well marginated towards bone and soft tissues (95%), either
      surrounded by a complete (84%) or incomplete (16%) rim of low signal intensity on
      images of all pulse sequences. Frequent features were polycyclic margins (84%),
      cortical expansion (87%), cystic spaces (100%), contrast-enhancing cyst walls
      (100%), internal septations (89%), fluid levels (71%) and diverticula-like
      projections of cyst walls (68%). Solid tissue components could be identified by
      MR imaging in all lesions which, on pathological examination, contained larger
      portions of solid material (18%). Edema of surrounding soft-tissues was observed
      in 29% of the cases. CONCLUSIONS: Primary aneurysmal bone cysts demonstrate a
      relatively uniform MR imaging appearance, which reflects the patho-anatomic
      composition of the lesion.

PMID- 10962983
TI  - [Pulse triggering for improved diffusion-weighted MR imaging of the abdomen].
AB  - PURPOSE: The aim of this work was to reduce the influence of motion on diffusion
      weighted MR images of the abdomen by pulse triggering of single-shot sequences.
      METHODS: Five healthy volunteers were examined both without and with finger pulse
      triggering of a diffusion-weighted single-shot echo planar MR imaging sequence at
      1.5 T. Series of diffusion-weighted images were acquired at different phases of
      the cardiac cycle by varying the time delay between finger pulse and sequence
      acquisition. The measurements were repeated three times. The diffusion weighted
      images were analysed by measuring the signal intensities and by determining the
      ADC values within the spleen, kidney and liver. RESULTS: The magnitude of motion
      artifacts on diffusion weighted images shows a strong dependence on the trigger
      delay. The optimum trigger delay is found to be between 500 and 600 ms. For these
      values the abdominal organs appear homogeneous on all diffusion weighted images
      and the strongest signal intensities are detected. At optimum triggering the
      accuracy of the apparent diffusion coefficients is up to 10 times better than
      without triggering. Moreover, the standard deviation of the repeated measurements
      is smaller than 12% for all volunteers and for all organs. Without triggering the
      standard deviation is larger by a factor of 4 on average. CONCLUSION: Pulse
      triggering of single-shot sequences leads to significant reduction of motion
      related artifacts on diffusion weighted images of the abdomen and provides more
      accurate and reproducible ADC values.

PMID- 10962986
TI  - [Computed tomographic appearance of pulmonary mucormycosis].
AB  - AIM: Analysis of the morphological characteristics of pulmonary mucormycosis
      using computed tomography (CT). MATERIAL AND METHODS: Prospective analysis of CT
      studies in 9 patients out of 19 patients with proven pulmonary mucormycosis.
      RESULTS: Pulmonary mucormycosis was most frequently found in the upper lobe
      bilaterally (51% of all nodules). In 22% of the manifestations, the morphological
      criterion of a "bird's nest" could be verified in CT, in 37% central necrotic
      areas were detected. In 37% an open bronchus was diagnosed, in 6% we observed
      bronchiectases. 43% of all nodules presented with a halo sign. In three patients
      we found pleural effusions, enlarged mediastinal lymph nodes were diagnosed in
      one patient. CONCLUSION: Computed tomography allows an improved diagnosis and
      therapeutic follow-up in patients suffering from pulmonary mucormycosis.

PMID- 10962985
TI  - [Magnetic resonance tomography in the diagnosis of intra-articular tibial plateau
      fractures: value of fracture classification and spectrum of fracture associated
      soft tissue injuries].
AB  - PURPOSE: To compare magnetic resonance imaging (MRI) and X-ray tomography in
      assessing the type of fracture, degree of comminution and amount of articular
      surface depression in acute tibial condylar fractures and to describe the
      associated soft tissue injuries diagnosed with MRI. METHOD: 27 patients with
      acute tibial plateau fractures were investigated using linear X-ray tomography
      and MRI employing T1-weighted and proton density turbo spin echo, STIR, and T2
      weighted gradient echo images. Fractures were classified according to the AO
      classification system. The degrees of depression and comminution were measured
      and soft tissue injuries were recorded. RESULTS: Fractures were classified as
      type B1 in 7, as B2 in 6, and as B3 in 6 cases by MRI. More complex C-type
      fractures were diagnosed in 8 cases. MR and X-ray grading were consistent with
      the exception of two B3 fractures, which were graded as B1 by X-ray tomography. X
      ray tomography under-estimated the degree of comminution 63% of the patients had
      either meniscal tears or complete ruptures of their cruciate or collateral
      ligaments. Ten meniscal tears were diagnosed in 9 of 27 patients. Complete tears
      of the anterior cruciate ligament were seen in 4, and avulsions of the posterior
      cruciate ligament in 2 patients. CONCLUSION: MRI allows a detailed assessment of
      acute tibial plateau fractures and can replace conventional X-ray tomography. The
      high rate of fracture-associated soft tissue lesions makes MRI an especially
      valuable tool.

PMID- 10962987
TI  - [Variability in the MR tomographic determination of myocardial function and
      perfusion parameters in health subjects].
AB  - PURPOSE: The aim of the study was to evaluate myocardial function and perfusion
      patterns using magnetic resonance imaging in normal subjects. MATERIALS AND
      METHODS: 22 healthy volunteers were examined. Cine-mode acquisitions along all
      three axes of the heart were generated and perfusion was measured on a mid
      ventricular short-axis view. Myocardial wall thickening was scored and contrast
      enhancement during the first pass was analysed. RESULTS: For myocardial wall
      thickening increasing values from base (24-86%) to apex (63-106%) were found.
      Contrast enhancement patterns showed regional variability. In addition marked
      individual differences were detectable. CONCLUSION: Perfusion patterns should be
      interpreted only in combination with functional parameters. Standard values for
      perfusion measurements cover very large range as a result of the high individual
      variability.

PMID- 10962988
TI  - [Evaluation of renal artery stenosis: comparison of angiography and invasive
      blood pressure measurement and Doppler ultrasound].
AB  - PURPOSE: In the procedure of renal artery angioplasty, the angiographically
      measured degree of stenosis should be compared with the intraarterial
      transstenotic blood pressure gradient and pre-interventional Doppler findings.
      METHODS: In a total of 46 renal arteries in 35 patients with renovascular
      hypertension, the angiographic-morphological parameters: "linear", "geometric"
      and "densitometric" degree of stenosis are compared with the invasive
      transstenotic blood pressure gradient and the pre-interventional Doppler
      ultrasound. RESULTS: All angiographically determined degrees of stenosis
      ("linear", "geometric" and "densitometric") correlate--moderately--with the
      transstenotic blood pressure gradient (correlation coefficients: 0.67 ("linear"),
      0.65 ("geometric") and 0.49 ("densitometric"), each versus systolic pressure
      gradient, respectively). Stenoses that are angiographically classified as "low
      grade" (< 50%) nevertheless have a high number of high transstenotic pressure
      gradients: 21 of 22 show systolic values > or = 10 mmHg, 13 of 22 even > or = 30
      mmHg. All stenoses Doppler sonographically classified as "high or very high
      grade" (Vmax,syst > or = 3 m/s) are confirmed by angiography and/or pressure
      measurement. CONCLUSIONS: Angiography has the tendency to underestimate the
      degree of renal artery stenosis, especially in "low grade" stenoses (< 50%).
      However, in those > or = 50% a high transstenotic blood pressure gradient can be
      taken for granted. If the angiographic degree of stenosis seems uncertain, we
      recommend measurement of blood pressure gradient.

PMID- 10962989
TI  - [Spectroscopic imaging (1H-2D-CSI) of the prostate: sequence optimization and
      correlation with histopathological results].
AB  - PURPOSE: Methodological optimization of a 1H MR spectroscopic imaging sequence
      (1H-2D-CSI) and evaluation of its potential to diagnose prostate cancer as
      validated by histopathological maps. METHODS: The prostates of 18 patients were
      evaluated by 1H-MR-CSI (voxel dimension: 1 cm3) at 1.5 Tesla. This sequence was
      additionally combined with a frequency selective fat suppression. RESULTS: It was
      possible to distinguish prostate carcinoma from prostate hyperplasia
      spectroscopically by the ratio of citrate/(choline + creatine). Differentiation
      of high-grade prostatic intraepithelial neoplasia (PIN, high-grade) from prostate
      carcinoma was not unambiguously possible. Prediction of tumor differentiation was
      not possible by the ratio of citrate/(choline + creatine) by our maximum spatial
      resolution of 1 cm3. CONCLUSION: 1H-2D-CSI is suitable for tumor detection. Tumor
      differentiation was not possible with the spatial resolution used.

PMID- 10962990
TI  - [Fusion of CT and PET data: methods and clinical relevance for planning laser
      induced thermotherapy of liver metastases].
AB  - AIM: Catheter-placement in liver metastases is difficult when the lesions are not
      visible on plain images. We evaluated the use of image fusion using CT and PET
      data, providing information on anatomy and liver lesions, respectively. METHODS:
      Plain CT of the liver and whole body FDG-PET were performed in 28 patients with
      colorectal carcinoma in preparation for laser-induced thermotherapy. Fusions of
      image data and 2D-visualisation were performed and evaluated with regard to
      quality of the registration, number of detected lesions and influence of the
      procedure on laser-induced thermotherapy. Image fusion was performed using an
      algorithm which was developed by our group. RESULTS: 84 focal liver lesions were
      visible on CT, 107 on PET images. This means that CT guided catheter placement
      would have to be performed "blindly" in 23 lesions. In 6 patients previously
      unknown extra-hepatic tumor deposits were seen on PET images (local recurrence, 2
      extrahepatic metastases, 2 second primaries). CONCLUSION: Hot spots from
      metastases, which are difficult to locate on PET images alone, may be identified
      on images generated by fusion of CT and PET data. These images facilitate an
      interventional approach to liver lesions which are not visible on plain CT. As
      PET allows for whole body screening, it helps identifying patients who would not
      profit from laser-induced thermotherapy.

PMID- 10962991
TI  - [Diagnosis of pre-occlusive stenosis of the internal carotid artery by power mode
      ultrasound].
AB  - PURPOSE: To evaluate the accuracy of power mode (PM) vascular ultrasound in
      preocclusive (> 90%) stenosis of the extracranial internal carotid artery (ICA)
      compared to other diagnostic methods and to operative findings. MATERIAL AND
      METHODS: 50 patients with preocclusive stenosis have been examined in a
      prospective study by power mode and color flow duplex ultrasound, by triplane
      aortic arch and four plane selective DSA. In 11 cases a MR angiography (time-of
      flight) was available. Diagnostic findings were compared to operative results.
      RESULTS: There was an agreement in findings in 50/50 patients (100%) for
      selective DSA, in 47/50 (94%) for power mode ultrasound, in 38/50 (76%) for
      aortic arch DSA, in 31/50 (62%) for color flow duplex ultrasound, and in 5/11 for
      MR angiography. In contrast to all other methods, ultrasound showed best the true
      extent of non-calcified atheromatous plaques. In extended vascular calcifications
      or kinking, however, only parts of the lumen of the vessel could be demonstrated.
      CONCLUSION: Power mode ultrasound shows preocclusive stenosis of the ICA in a
      faster and more simple way than color flow duplex ultrasound and has diagnostic
      results near to those of selective DSA. It improves preoperative diagnostic
      screening.

PMID- 10962992
TI  - [Tissue harmonic imaging in comparison with conventional sonography: effect on
      image quality and observer variability in the measurement of the intima-media
      thickness in the common carotid artery].
AB  - OBJECTIVE: The purpose of this study was to determine if tissue harmonic imaging
      (THI) produced a higher image quality than conventional sonography and if THI
      reduced the observer availability in the intima media thickness (IMT)
      measurements of the common carotid artery (ACC). SUBJECTS AND METHODS: A
      prospective study was performed on 26 healthy volunteers and IMT was assessed by
      three experienced sonographers in 52 carotid arteries. A 7.5 MHz transducer was
      used to measure carotid IMT in both harmonic and fundamental modes. Three
      measurements of IMT were carried out on the far wall of the ACC along a 1 cm-long
      section proximal to the bifurcation. Image quality was graded from 1-3 (1 =
      excellent, 2 = good, 3 = poor). IMT measurements using harmonic and fundamental
      modes were compared and intra- and inter-observer variability were calculated.
      Statistical analyses were performed using a kappa analysis, ANOVA and the
      McNemar/Wilcoxon Test. RESULTS: In the 52 cases image quality was excellent in
      51% using THI in comparison to 32% using conventional sonography. Image quality
      was graded significantly more frequent as excellent using harmonic sonography as
      compared to conventional sonography (p = 0.001). A significant difference in IMT
      was found between the measurements obtained by harmonic imaging in comparison to
      those obtained by conventional imaging (p < 0.0001). Using the harmonic mode
      inter-observer variability of the IMT measurements was significantly reduced from
      8.1% to 5.2% (p < 0.001). CONCLUSIONS: THI produced a higher image quality with a
      better visualisation of carotid IMT and reduced significantly the intra- and
      inter-observer variability in the IMT measurements.

PMID- 10962993
TI  - [Full-field digital mammography: a phantom study for detection of
      microcalcification].
AB  - OBJECTIVES: The study compares direct full-field digital mammography (FFDM) to
      the state-of-the-art conventional screen-film mammography (SFM) concerning the
      detectability of simulated microcalcifications. MATERIALS AND METHODS: The
      investigations were performed with a FFDM system (Senographe 2000D, GEMS) and a
      SFM system (Senographe DMR, GEMS, Fuji UM MA film with Fuji UM MAMMO FINE
      screen). An anthropomorphic breast phantom with superimposed microcalcifications
      (50-200 microns) was used to evaluate the detectability of microcalcifications
      with a confidence level ranging from 1 to 5. Contact mammograms and magnification
      spot views (m = 1.8) of the FFDM and SFM systems were compared. A receiver
      operating characteristic (ROC) analysis was performed by three well-experienced
      readers. RESULTS: The ROC analysis revealed a higher performance of the digital
      images compared to the conventional screen-film mammograms. The area under the
      ROC-curve (Az) in the digital contact mammograms was 0.68 versus 0.63 in the
      conventional technique. The results were not significantly different. In digital
      spot views, Az was 0.79 versus 0.70 in the conventional spot views. CONCLUSIONS:
      The results suggest that FFDM is at least equivalent or--as far as spot views are
      concerned--may be superior to conventional SFM in the detection of
      microcalcifications.

PMID- 10962995
TI  - [Radiotherapeutic strategies in the multimodal therapy of resectable and
      nonresectable pancreatic carcinoma].
AB  - BACKGROUND: The prognosis of patients with adenocarcinoma of the pancreas remains
      poor. Only patients with small tumors and complete resection have a curative
      chance. The value of combined radio-chemotherapy adjuvant or even palliative in
      case of unresectable tumors is controversial due to the short median survival
      times of all patients ranging from 8 to 15 months. Within the last years,
      significant new treatment modalities were introduced into the multimodality
      approach. Even the intraoperative boost therapy (IORT) with fast electrons
      remains still controversial. MATERIAL AND METHODS: Since the publication of the
      results of the historic GITSG study, in the US postoperative adjuvant radio
      chemotherapy with 5-FU remains the treatment of choice. Successor studies of the
      ESPAC and the EORTC have been closed or are recruiting patients, the results are
      still pending. Neoadjuvant treatment modalities were investigated within the last
      3 years, mostly in case of primary operable but also in unresectable tumors.
      Using 3-D-treatment planning, the total dose of radiotherapy was increased from
      40 up to 45 to 50 Gy. In centers with great experience, an IORT was added to
      these combined modalities. More modern chemotherapeutic agents like gemcitabine
      or the taxanes are under investigation, using combined radio-chemotherapy in
      phase-II protocols in patients with unresectable tumors. RESULTS: In case of
      both, adjuvant or neoadjuvant radio-chemotherapy following or before
      pancreaticoduodenectomy, median survival times range from 15 to 25 months. The
      neoadjuvant radio-chemotherapy seems to reduce the rate of positive surgical
      margins and the rate of patients with positive lymph nodes. For the moment, there
      is no proven survival advantage or increase of local control (about 80% in both
      cases) for patients treated with neoadjuvant radio-chemotherapy compared with
      adjuvant radio-chemotherapy. However, about 25% of the patients don't receive
      adjuvant therapy due to the perioperative morbidity. Because prolongation of
      survival with adjuvant therapy is only 5 to 10 months, in Europe adjuvant radio
      chemotherapy is not accepted as the treatment standard. Combined radio
      chemotherapy in patients with unresectable tumors results in significant
      improvement of survival. 5-FU continuous infusion with 250 mg/m2 seems to be the
      treatment of choice. IORT is effective in achieving long-term local control and
      an effective pain palliation. More modern chemotherapeutic agents seem to be
      effective in vitro as radio-sensitizers. In first reported results, the MTD was
      not found. Toxicity seems not to be increased with single radiotherapy doses of
      1.8 to 2 Gy. However, higher single doses should not be used. CONCLUSIONS: Due to
      the worse prognosis of patients with adenocarcinoma of the pancreas, new combined
      treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly
      with more modern chemotherapeutic agents, for patients with resectable and
      unresectable tumors are under investigation. For some reasons, the neoadjuvant
      setting seems to be better. However, these results are not proven by prospective
      randomized clinical trials. Therefore, these trials are necessary to define the
      treatment of choice in these patients. IORT is a helpful tool to improve local
      control. However, these aggressive multimodality approaches are only indicated in
      a minority of patients. In patients with unresectable tumors and good condition,
      combined radio-chemotherapy remains the treatment of choice.

PMID- 10962994
TI  - [Percutaneous transjugular thrombectomy in iliocaval thrombosis-- initial
      experience with a newly developed 12F balloon sheath].
AB  - PURPOSE: To evaluate the feasibility of percutaneous thrombectomy for the removal
      of floating iliocaval thrombi using a balloon sheath. MATERIALS AND METHODS: A
      newly developed balloon sheath (inner diameter: 12-F; outer diameter: 18-F) was
      tested in two patients with extensive iliocaval thrombosis. Mechanical
      thrombectomy was performed due to recurrent pulmonary embolism under therapeutic
      anticoagulation in antiphospholipid-antibody syndrome and, respectively,
      paraneoplastic thrombosis without a decrease of fresh thrombus mass in spite of
      pharmacological treatment. Via a transjugular access (20-F), the sheath was
      advanced retrogradely into the inferior vena cava. After blocking of the vessel,
      mechanical fragmentation was performed through the working channel coaxially,
      using a temporary vena cava filter as a rotating basket (max. diameter: 30 mm).
      Residual thrombus fragments were removed by aspiration. RESULTS: The thrombectomy
      balloon sheath tested allowed a complete removal of fresh thrombi after
      fragmentation. In addition, older clot material was obtained. Balloon occlusion
      prevented the central embolization of thrombus fragments. Clinical signs
      indicating pulmonary embolism were not seen. The fluid loss due to aspiration was
      negligible. CONCLUSIONS: The newly developed 12-F balloon sheath proved to be
      efficient for the extraction of large thrombi. Balloon occlusion safely prevented
      central embolization of thrombus fragments proximal to the sheath.

PMID- 10962996
TI  - Sentinel node concept in breast cancer.
AB  - BACKGROUND/PURPOSE: It seems that there exists a specific lymph node center
      called sentinel node (SN) which appears to be the primary site of metastases. The
      sentinel node concept (SNC) is fundamentally based on the orderly progression of
      tumor cells within the lymphatic system. It is the most important new concept in
      surgical and radiation oncology. The purpose is to present the biological
      significance, the diagnostic and clinical basis of the sentinel node concept in
      breast cancer patients. MATERIAL AND METHODS: Lymphoscintigraphy and gamma probe
      biopsy is necessary to show predictable lymph flow to the regional sentinel node,
      to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel
      nodes and for performing sentinel node procedure. The standard protocol for the
      evaluation of the sentinel node metastases consists of extensive
      histopathological investigation including step Hematoxylin & Eosin (H&E) stained
      sections and immunohistochemistry. RESULTS: A high rate of success of the
      identification of the sentinel node for breast cancer was reported. The presence
      or absence of metastasis in this node is a very accurate predictor of overall
      nodal status. The temptation to examine the sentinel node with the greatest
      possible degree of accuracy highlights one of the major problems related to
      sentinel node biopsy. The success of the sentinel node procedure depends
      primarily on the adequate functional capacity necessary for sufficient uptake to
      ensure the accurate identification. In negative sentinel-node patients a complete
      axillary lymph node dissection is avoidable. In sentinel-node positive patients
      and clinically negative patients a postoperative radiotherapy would permit an
      adequate tumor control. The last 2 procedures permit a low morbidity. In the
      actual TNM classification it was recently introduced a definition of a "pN0"
      patient based on sentinel node biopsy. New target volumes are defined for
      adjuvant radiotherapy or lymphatic basins could be spared from unnecessary
      irradiation. CONCLUSION: The sentinel node concept seems to revolutionize the
      treatment of early breast cancer. Biopsy of the sentinel node is a highly
      accurate, minimally invasive method of staging patients and can substantially
      reduce the morbidity and costs of treatment by avoiding unnecessary complete
      axillary lymph node dissection. The procedure may lead to a more justifiable
      approach to adjuvant therapy strategies with low complication rates. The
      identification of the individual lymphatic flow pattern would permit the
      irradiation of the individual locoregional lymphatic basin.

PMID- 10962997
TI  - Variation in "supraclavicular" lymph node depth is partly determined by treatment
      position.
AB  - BACKGROUND: The so-called "supraclavicular" region bears the confluence of deep
      jugular, upper mediastinal and axillary lymph node groups and therefore it is
      often part of the target volume in common malignancies like lung cancer, breast
      cancer and head and neck cancer. For treating this area, several authors
      recommend an anterior portal with the dose prescribed to a tissue depth of 3 cm,
      which does not fit our institution's experience. PATIENTS AND METHODS: In 119
      consecutive patients a computed tomography for planning purposes was performed.
      We used the subclavian blood vessels between clavicula and first rib as an
      estimate of the confluence of the mentioned lymph node regions and determined
      their tissue depth (which does not describe the deepest part of the lymph
      vessels). RESULTS: Mean and median of the tissue depth were 5 cm in a range from
      2 to 9 cm. Only in less than 20% of the measurements we found the vessels located
      3 cm or less under the surface which would correspond to a depth of the lymph
      node target volume 4 to 5 cm. Increasing body mass resulted in deeper location of
      the vessels. The position of the patient's arms influenced the tissue depth even
      more. Arms risen above the head resulted in 55% of the measurements in tissue
      depths of 6 cm or deeper compared to 6% in patients treated with arms beside the
      body. CONCLUSION: Standardized treatment prescriptions do not cope adequately
      with individual anatomy. Treatment position especially of the arms influences
      location of the "supraclavicular" lymph node region in thoracic treatment. Target
      volume delineation by computed tomography seems the most accurate solution,
      although it is the most expensive one. Patient immobilization is crucial for
      accuracy of treatment delivery.

PMID- 10962998
TI  - Chromosomal aberrations induced in mice bone marrow by treating with cisplatin
      and irradiation.
AB  - BACKGROUND: The aim of this study was to quantify the combined effect of
      cisplatin and radiation on chromosomal damage with emphasis on the time interval
      between cisplatin and radiation. METHODS AND MATERIALS: Bone marrow of female
      NMRI-nu(+) mice was taken as a model system for a highly proliferative tissue
      irradiated with cobalt-60 (1 to 4 Gy). Cisplatin was injected intraperitoneally
      (i.p.) at 1.1 to 36 mg/kg. Cisplatin was given at various time intervals before
      and after radiation. Bone marrow and metaphases were prepared according to
      standard procedures. RESULTS: The percentage of aberrant metaphases after
      radiation or cisplatin alone increased in a dose-dependent manner (sigmoidal dose
      response curve). Combining both modalities led to additive values at all time
      points for the percentage of aberrant metaphases. Borderline significant (p <
      0.05) supraadditive effects were found 2 hours before or 1 hour after
      irradiation. However, a supraadditive percentage of aberrant chromosomes was
      found only at 2 or 1.5 hours with cisplatin before irradiation indicating the
      dependence of supraadditivity on the chosen parameter. CONCLUSION: It is doubtful
      to expect a true supraadditive or "radiosensitizing" effect, e.g. in the clinical
      setting from combined treatment with cisplatin and radiation. Rather, cisplatin
      might act as an independent cytotoxic agent.

PMID- 10962999
TI  - Aggressive angiomyxoma: irradiation for recurrent disease.
AB  - BACKGROUND: Aggressive angiomyxoma (AAM) is a tumor of the soft tissues
      predominately occurring in the genital and pelvic area with a strong propensity
      to local recurrences. The entity was first described in 1983. The tumor is
      regarded as low-grade sarcoma by some authors; its cause and pathogenesis are
      presently unknown. PATIENT AND METHOD: This is a case report on a 27-year-old man
      who underwent 4 surgical procedures of the left lower extremity because of a
      recurrent soft tissue neoplasm, initially (August 1993) diagnosed as a
      myxolipoma. The patient suffered from recurrences in February 1995, September
      1996 and February 1998. The diagnosis was revised at the time of the latest
      recurrence. A palliative resection with macroscopic residuals left was performed
      in February 1998, followed by a radiation therapy with 56 Gy total dose and a
      concomitant administration of the radiosensitizer razoxane per os. The single
      radiation doses were 200 cGy 5 times a week. RESULTS: The small residuals of the
      tumor obviously regressed although an objective response could not be shown
      because the lesion was not clearly measurable. A follow-up 2 years after the
      radiation treatment revealed no recurrence. The time of the local control
      achieved as yet is already longer than any former time to regrowth between the
      surgical procedures. This is, to our knowledge, the first description of a
      therapeutic irradiation of a recurrent aggressive angiomyxoma. CONCLUSION:
      Radiation therapy combined with the sensitizer razoxane is able to control a
      recurrent AAM for an unknown time. It remains open whether a radiation treatment
      alone would have had a similar effect.

PMID- 10963000
TI  - [Optimized 3-D planning by simple means. An example].
AB  - AIM: A treatment technique favorable for linacs with asymmetric jaws, which
      combines cranio-caudal matching fields with fields enclosing the whole target
      volume, is investigated with respect to field matching and sparing of normal
      tissue and organs at risk. PATIENT AND METHODS: For a pelvic target volume
      rapidly varying in cranio-caudal direction a 5-field technique was planned with
      individually weighted and blocked fields. Three fields adjoining in cranio-caudal
      direction were completed by 2 fields enclosing the whole target volume. The
      matching line was measured and calculated with Helax TMS. Furthermore a 4-field
      box and opposing fields were planned. The dose-volume histograms for target,
      bladder, intestine and soft tissue were exported. Normal tissue complication
      probability and tumor control probability, respectively, were calculated for all
      techniques. RESULTS: In the region of the matching line the summation of the
      measured normalized curves resulted in relative dose maxima of 6.0% (caudal) and
      4.5% (cranial), respectively. For fields enclosing the whole target volume the
      dose maxima in the region of the matching line decreased to 2.0% (caudal) and
      1.8% (cranial), respectively. For the dose profiles calculated with Helax TMS no
      overdose was found. The 5-field technique with adjoining fields results in a
      better sparing of the organs at risk compared to the other techniques, whereas
      the tumor control remains the same. CONCLUSIONS: In specific cases a technique
      with cranio-caudal adjoining fields can be recommended with respect to sparing of
      normal tissue and organs at risk.

PMID- 10963001
TI  - [High-dose chemotherapy for metastatic breast cancer without certain advantages
      so far].

PMID- 10963002
TI  - [Pregnancy and risk of early breast cancer in patients sith BRCA1 and BRCA2
      mutations].

PMID- 10963003
TI  - [Cancer during pregnancy].

PMID- 10963004
TI  - [Abdominal neuroblastoma. Recent findings on diagnosis and treatment].

PMID- 10963005
TI  - [Wilms' tumor. Diagnosis and treatment].

PMID- 10963006
TI  - [Gastroesophageal reflux].

PMID- 10963007
TI  - [Congenital intestinal motility disorders].

PMID- 10963008
TI  - [Disorders of fecal continence in children. Function-based incontinence].

PMID- 10963009
TI  - [Disorders of fecal continence in children. Organ-based incontinence].

PMID- 10963010
TI  - [Bacterial infections and resistance to antibiotics in cystic fibrosis].
AB  - Knowledge of the microbiology of pulmonary infections is critical for treatment
      of cystic fibrosis because sickness and mortality in this disease are mainly due
      to relapse occurring in the respiratory tract. The microbiology of pulmonary
      infections presents several singular aspects. Respiratory tract infections are
      caused by bacteria such as Staphylococcus aureus in the early years of life and
      Pseudomonas aeruginosa and Burkholderia cepacia thereafter. The patients, who are
      not immune compromised, are predisposed to chronic colonization and highly
      transmissible bacterial strains can cause cross-infections. Bacterial also
      develop resistance mechanisms which make them difficult to treat. Until recently
      the relationship between genetic defects and a predisposition to colonization was
      not noted, but recent studies have allowed us to form some interesting
      hypothesis. The present work analyzes the principal mechanisms of antibiotic
      resistance, with particular reference to classic cystic fibrosis pathogens, and
      looks at future prospects of respiratory tract infection treatment.

PMID- 10963011
TI  - [Prevalence of anti-HAV antibodies (hepatitis A virus) in 18-year-old males from
      the Florence area].
AB  - In 1998 sera from 430 18 year old male subjects living in "Florentina area" have
      been tested for anti-hepatitis A virus (HAV) antibodies. 27 out of 430, (6.2%),
      study samples were found to be positive. Our results confirm the low circulation
      rate of HAV in Florence area.

PMID- 10963012
TI  - [Pathogenesis of neoplasms].
AB  - The Authors discuss the aspect and the function of the Microcirculatory Unit and
      the chronic reduction of circulation in true capillaries and therefore of tissue
      perfusion increasingly evident with the advancement of age, the structural
      simplification of proteins, the instability of the cells' genome and the
      increasing remoteness of the immunity system's control. In view of these
      considerations, they propose the possibility that the onset of tumours may be due
      to the accentuation of mutageneous substances and the reduction of tissue
      perfusion with age. When perfusion is maintained of periodically resumed, hypoxy
      only determines hyperplasia but not cell degeneration or mutations.

PMID- 10963014
TI  - [Cecal duplication: unusual cause of acute abdomen in children. Report of a
      case].
AB  - The Authors describe a rare cause of cecal duplication cyst in children: because
      of the inflammatory clinical finding, an emergency operative intervention is
      made. Ultrasonic preoperative diagnosis is evaluated.

PMID- 10963013
TI  - [Coexistence of cystic fibrosis and celiac disease. Description of a clinical
      case and review of the literature].
AB  - A 14-month-old female infant with chronic diarrhea, recurrent respiratory
      infections and stunted growth was diagnosed as celiac disease with AGA detection
      and a positive intestinal biopsy. A gluten-free diet was introduced with a poor
      response. A sweat test was positive and heterozygosis for mutation of CFTR gene
      (both F508 and G542X) was found, demonstrating an association in the infant
      between cystic fibrosis and celiac disease. Fifteen cases of such association
      have been previously described in literature, but only three have been
      genetically studied. The co-existence of cystic fibrosis and celiac disease in
      the same subject has to be considered till now a casual finding, but are also
      discussed hypothesis of a non-casual linkage, formulated by some authors.

PMID- 10963015
TI  - [Abnormalities in newborns of mothers with antiphospholipid antibody syndrome.
      Report of a case].
AB  - We described the case of a newborn, whose mother was affected by anti
      phospholipids antibodies syndrome and had previously had several abortions. The
      newborn presented emispondilitis. (We suppose it is important to notice that
      cases like this have never been signalled in literature so far).

PMID- 10963016
TI  - [Hypertensive encephalopathy in post-infective glomerulonephritis].
AB  - We described the case of a thirteen years old boy who came to our observation
      because of ematuria, orbital oedema, headache and hypertension (with renal
      symptoms). In few hours this syndrome evolved in a serious hypertensive
      encephalopathia with convulsions and emiparesis.

PMID- 10963017
TI  - Tense and finiteness in the speech of children with specific language impairment
      acquiring Hebrew.
AB  - Verb morphology is often an area of extraordinary difficulty for children with
      specific language impairment (SLI). However, in Hebrew, this difficulty appears
      to be more circumscribed than in other languages. In a recent study by Dromi et
      al., the limitations exhibited by a group of Hebrew-speaking children with SLI
      were confined primarily to the use of agreement inflections within past tense.
      This difficulty was interpreted as being due to the fact that the agreement
      paradigm within past tense is rather complex (involving person, number, and
      gender, along with tense). This study explores another possibility--that these
      inflections were difficult because they required past tense in particular. Also
      determined was whether the children's frequent use of the morphologically
      simplest forms (such as past third person masculine singular) in place of the
      correct forms could be interpreted as their selection of a non-finite default
      form. A group of Hebrew-speaking children with SLI (age 4.2 to 6.1) participated,
      along with a group of age controls, and a group of younger normally developing
      children matched for mean length of utterance (MLU). The children listened to
      stories that were accompanied by pictures. During each story, the children
      completed the experimenter's incomplete sentences using appropriate verbs. To
      complete the sentences accurately, the children had to alter the tense or
      finiteness of the verb used by the experimenter in the preceding sentence. The
      results indicated that the children with SLI had more difficulty than both
      comparison groups in the production of basic present and past forms and
      infinitive forms of verbs that required use of one particular phonological
      template or 'binyan'. However, for the verbs requiring the remaining three
      phonological templates, the children with SLI were as capable as MLU controls in
      their command of past as well as present tense, and in their use of infinitive
      forms. It is concluded that tense and finiteness probably do not form the core of
      the problem faced by Hebrew-speaking children with SLI in the area of verb
      morphology.

PMID- 10963018
TI  - Phonological awareness therapy and articulatory training approaches for children
      with phonological disorders: a comparative outcome study.
AB  - Sixty-one children, aged 3.6-5.0, with developmental phonological disorders (PD)
      participated in a study comparing the effects of metaphonologically (MET) or
      articulation-based (ART) therapy. Maturational effects were controlled for by the
      inclusion of 59 normally speaking control children of the same age range.
      Measures of phonological (speech) output and phonological awareness were taken
      before and after therapy for all subjects and at 3 months post-therapy for PD
      children. Results showed that PD children improved significantly in both
      phonological output and awareness skills across the intervention period compared
      with control children, but that there was no significant difference on the
      awareness measure between ART and MET groups. ART and MET groups differed from
      each other on one measure of speech improvement only, with the ART group making
      more change than the MET group on individual probe scores. Follow-up measures for
      both therapy groups indicated that there was little difference between the groups
      on phonological awareness change or speech development 3 months after
      intervention, though there was a trend for MET children to continue to make more
      long-term change than the ART group on one output measure. Additional analysis
      showed that there were generally few significant implications for outcome between
      PD children with good initial phonological awareness skills and those who
      initially had poor phonological awareness skills.

PMID- 10963019
TI  - Examining interaction in language therapy.
AB  - Discussions around a 'theory of therapy' have prompted attempts to delineate the
      components of therapy for language impairment in aphasia. Here it is suggested
      that the therapy components associated with how language therapy is enacted need
      more precise specification, especially in relation to what is entailed by
      interaction between therapist and person with aphasia. Presented too is a system
      used for the analysis of interaction in language impairment therapy for aphasia
      and its possible applications are discussed. Components of the system are
      described and a sample analysis presented. The methodological difficulties
      entailed in making comparisons of therapy enactment are discussed. It is
      suggested furthermore that unless more is known about precisely defined
      interactions in therapy, it will be difficult to answer basic questions not only
      about how language therapy is being carried out, but also, subsequently, whether
      the ways in which therapy tasks are enacted have a significant impact on the
      outcome.

PMID- 10963020
TI  - Parkinson's disease and aided AAC: some evidence from practice.
AB  - Clinical observation that people with Parkinson's disease (PD) seem to have
      different training needs from other adult client-groups in developing effective
      use of aided augmentative and alternative communication (AAC) was the catalyst
      for this study. There is little good-quality research evidence available on the
      effectiveness (or lack of effectiveness) of aided AAC use by those with PD. One
      of the main aims of this preliminary study, therefore, was to elicit the
      experiences and attitudes of speech and language therapists in this specific area
      of their practice as the basis for future efficacy research and clinical
      practice. Thirty speech and language therapists were questioned about their
      experience of introducing low- and high-tech AAC devices to this client-group. Of
      particular interest was the discovery of the factors identified by the therapists
      as influencing their introduction of aided AAC to someone with PD and affecting
      implementation and successful use. The factors reported were both disease
      specific (e.g. motor problems) and more general factors (e.g. carer support)
      relevant to the process of introducing aided AAC to other adult client-groups.
      Implications for future research and practice are discussed. Some research
      questions are posed and the inclusion of people with PD and their carers in
      practice development is promoted.

PMID- 10963021
TI  - Investigating parental views of involvement in pre-school speech and language
      therapy.
AB  - Today, speech and language therapists working with the pre-school population
      routinely involve parents in their children's treatment programmes. Also, there
      is increasing recognition of the importance of considering client and carer views
      in evaluating services. Thus, in both clinical and research terms, the role of
      parents is key. This paper reports an aspect of a study that investigated
      parents' views and perceptions of their pre-school children's speech and language
      difficulties and the speech and language therapy (SLT) they received. The
      methodology of the study was qualitative and data were collected from the parents
      of 16 pre-school children, using in-depth interviews. The parents' perceptions
      could be characterized as a process with three phases. On the whole, parents
      viewed their involvement in SLT positively but crucially, the interviews
      highlighted discrepancies between therapists' and parents' perceptions of the
      therapy process. The study demonstrates that when parents' views are considered,
      a fuller understanding of the effectiveness and acceptability of treatment can
      emerge.

PMID- 10963022
TI  - Voice characteristics in the progression of Parkinson's disease.
AB  - This study examined the acoustic and perceptual voice characteristics of patients
      with Parkinson's disease according to disease severity. The perceptual and
      acoustic voice characteristics of 30 patients with early stage PD and 30 patients
      with later stage PD were compared with data from 30 normal control subjects.
      Voice recordings consisted of prolongation of the vowel /a/, scale singing, and a
      1-min monologue. In comparison with controls and previously published normative
      data, both early and later stage PD patients' voices were characterized
      perceptually by limited pitch and loudness variability, breathiness, harshness
      and reduced loudness. High modal pitch levels also characterized the voices of
      males in both early and later stages of PD. Acoustically, the voices of both
      groups of PD patients demonstrated lower mean intensity levels and reduced
      maximum phonational frequency ranges in comparison with normative data. Although
      less clear, the present data also suggested that the PD patients' voices were
      characterized by excess jitter, a high-speaking fundamental frequency for males
      and a reduced fundamental frequency variability for females. While several of
      these voice features did not appear to deteriorate with disease progression (i.e.
      harshness, high modal pitch and speaking fundamental frequency in males,
      fundamental frequency variability in females, low intensity and jitter),
      breathiness, monopitch and monoloudness, low loudness and reduced maximum
      phonational frequency range were all worse in the later stages of PD. Tremor was
      the sole voice feature which was associated only with later stage PD.

PMID- 10963023
TI  - Stroboscopic articulography using fast magnetic resonance imaging.
AB  - A method to display dynamic aspects of vocal tract configuration during speech
      production by means of fast magnetic resonance imaging is presented. Data
      acquisition during repetitive movement relies on a stroboscopy-like procedure.
      The time resolution achieved is 120 images s-1 in a selected plane. As compared
      with other techniques of kinematic measurements of speech motor processes, this
      procedure allows for visualization of the temporal and spatial coordination of
      all relevant articulators, e.g. the entire tongue, the velum and the lower vocal
      tract. As an example, the method was applied to repetitions of stop consonant
      vowel-nasal syllables.

PMID- 10963024
TI  - Voice problems in female-to-male transsexuals.
AB  - Voice therapy with the aim of raising a client's fundamental frequency is a
      common practice in the reassignment of male-to-female transsexuals. In female-to
      male transsexuals on the other hand voice therapy is usually not considered since
      the administration of androgens is assumed automatically to change the voice in
      the direction of the desired sex. The present study examined whether the voice
      change in female-to-male transsexuals is indeed as straightforward as it is
      assumed. Results from a sample survey involving 16 female-to-male transsexuals
      and longitudinal data from two clients suggest that the voice change in female-to
      male transsexuals is not always totally unproblematic. A voice assessment and
      some counselling before the hormone therapy are recommended.

PMID- 10963025
TI  - 10th Congress of the International Society for Biomedical Research on Alcoholism.
      Yokohama, Japan, 2-8 July 2000. Abstracts.

PMID- 10963026
TI  - 2000 Scientific meeting of the Research Society on Alcoholism. Santa Barbara,
      California, USA. 24-29 June 2000. Abstracts.

PMID- 10963028
TI  - 5th Congress of the European Society of Contact Dermatitis. Amsterdam, The
      Netherlands, 11-13 May 2000. Abstracts.

PMID- 10963029
TI  - 44th Symposium of The German Society of Endocrinology and 35th annual meeting of
      the German Society of Diabetes. Munich, May 31-June 3, 2000. Abstracts.

PMID- 10963027
TI  - 4th International Workshop on HIV Drug Resistance and Treatment Strategies.
      Sitges, Spain, 12-16 June 2000. Abstracts.

PMID- 10963031
TI  - 6th International Congress of Parkinson's Disease and Movement Disorders.
      Barcelona, Spain, June 11-15, 2000. Abstracts.

PMID- 10963032
TI  - 84th Meeting of the German Society of Pathology. Kiel, Germany, 7-10 June 2000.
      Abstracts.

PMID- 10963030
TI  - IASL-APASL Joint meeting. Fukuoka, Japan, 2-7 June 2000. Abstracts.

PMID- 10963033
TI  - Maintaining Lung Health from Cradle to Grave. Annual scientific meeting of the
      Thoracic Society of Australia and New Zealand. Melbourne, Australia, 7-12 April
      2000. Abstracts.

PMID- 10963034
TI  - Frontiers of Respiratory Medicine. Annual scientific meeting of the Thoracic
      Society of Australia and New Zealand. Adelaide, South Australia, 15-18 March
      1998. Abstracts.

PMID- 10963035
TI  - [XLII Congress of the French National Society of Internal Medicine. Aix-en
      Provence, 8-10 June 2000. Abstracts].

PMID- 10963036
TI  - Swedish Association of Urology annual meeting. Stockholm, December 1-2, 1999.
      Abstracts.

PMID- 10963037
TI  - 68th Annual meeting of the Swiss Society of Internal Medicine, annual meeting of
      the Swiss Society of Hematology, Swiss Professional Society of Geriatrics, and
      the Clinical Pharmacology Section. Zurich, 9-11 March 2000. Abstracts.

PMID- 10963038
TI  - The 7th Workshop and Conference on Human Leucocyte Differentiation Antigens (HLDA
      7). Harrogate, United Kingdom, 20-24 June 2000. Abstracts.

PMID- 10963039
TI  - Normal development of thymus in male and female mice requires estrogen/estrogen
      receptor-alpha signaling pathway.
AB  - Estrogen receptors (ERs) are expressed in the thymus of both males and females,
      but their role in thymic development and function is unclear. To determine
      whether ERalpha plays a role in thymic function of either males or females, we
      compared thymuses of male and female wild-type (WT) and ERalpha knockout
      (alphaERKO) mice from birth to adulthood. Although thymic size was similar in
      both male and female WT and alphaERKO mice at birth (d 0), by postnatal d 5 and
      at all subsequent ages, both male and female alphaERKO mice had significant (30
      55%) reductions in thymic weight. Morphometric analysis revealed a reduction in
      thymic medullary areas in adult alphaERKO mice compared with age-matched WT
      controls that paralleled thymic involution. There were changes in relative
      percentages of CD4+ and CD4+CD8+ T-cells, and large decreases (70-80%) in overall
      absolute numbers of CD4+ and CD4+CD8+ T-cells. Serum corticosterone and
      testosterone levels were not different in either neonatal or adult male WT or
      alphaERKO mice, and serum levels of 17beta-estradiol (E2) were similar in
      neonatal WT and alphaERKO males, indicating that increases in these thymolytic
      hormones are not responsible for the decreased thymic weight in alphaERKO males.
      Additionally, delayed-type hypersensitivity was significantly increased in male
      alphaERKO mice compared with WT mice. In summary, ERalpha deficiency does not
      inhibit initial differentiation or fetal thymic development, but the absence of
      ERalpha results in marked decreases in thymic size in both sexes during the
      postnatal period. These results are the first direct demonstration that the
      E2/ERalpha signaling system is necessary for maintenance of normal postnatal
      function of the female thymus gland. The similar results obtained in males
      demonstrate a role for the E2/ERalpha signaling system in the male thymus and
      emphasize that estrogens play a more critical role in the male than previously
      realized.

PMID- 10963040
TI  - Analyses for susceptibility of rat anterior pituitary cells to prolactin
      releasing peptide.
AB  - We validated the effect of prolactin-releasing peptide (PrRP) on prolactin (PRL)
      secretion from rat anterior pituitary cells in in vitro culture. We found that
      culture conditions considerably influenced the response of the anterior pituitary
      cells to PrRP. Longer culture term (4 d) was required to obtain better responses
      of the anterior pituitary cells to PrRP in comparison to thyrotropin-releasing
      hormone (TRH). Under the culture conditions employed here, PrRP was comparable to
      TRH in the potency promoting PRL secretion, and the action of PrRP was very
      specific for PRL secretion. The susceptibility of the anterior pituitary cells to
      PrRP varied in female rats depending on the process of reproduction: the cells
      prepared from lactating rats were the most sensitive to PrRP compared with those
      from random-cycle and pregnant rats. Because the expression levels of PrRP
      receptor mRNA in the pituitary varied during the reproductive process, we
      speculated that the susceptibility of the anterior pituitary cells would reflect
      cellular changes including the expression level of PrRP receptors. In addition,
      treatment with estrogen in vivo enhanced the susceptibility of the cultured
      anterior pituitary cells in male rats. Our results indicate that the
      susceptibility of the rat anterior pituitary cells to PrRP is regulated by
      physiological mechanisms.

PMID- 10963041
TI  - A newly recognized germline mutation of MEN1 gene identified in a patient with
      parathyroid adenoma and carcinoma.
AB  - We report on a patient with primary hyperparathyroidism, owing to the concurrence
      of parathyroid adenoma with carcinoma, who had a newly recognized germline
      mutation of the multiple endocrine neoplasia type 1 gene (MEN1 gene). The patient
      underwent total parathyroidectomy, and histological examination revealed
      parathyroid carcinoma and multiple adenoma of the other three glands. Genetic
      analysis revealed a newly recognized heterozygous germline mutation (842delC,
      exon 4) of the MEN1 gene. Both imaging studies and laboratory data showed no
      evidence of MEN1 in the patient. Four family members--three sisters and one
      daughter--had neither clinical features of MEN1 nor genetic evidence of the MEN1
      gene. This is the first report of a germline mutation of the MEN1 gene found in a
      patient who exhibited the concurrence of parathyroid adenoma with carcinoma,
      suggesting that long-term hyperactivity of the parathyroids may result in the
      formation of carcinoma.

PMID- 10963042
TI  - Induction of rat interstitial collagenase (MMP-13) mRNA in a development
      dependent manner by parathyroid hormone in osteoblastic cells.
AB  - The purpose of this study was to determine whether the production of interstitial
      collagenase mRNA in response to parathyroid hormone (PTH) changes with osteoblast
      phenotypic development. To accomplish this, cells derived from fetal rat calvaria
      were examined. The calvarial osteoblasts, which proliferate when placed in
      culture, can be made to differentiate after confluence. Studies were performed on
      cells while they were proliferating, at confluence, and during the
      differentiation process. The cells were treated with PTH for various times, and
      interstitial collagenase mRNA was quantified by RNase protection assay. We
      concluded that the ability of PTH to induce interstitial collagenase mRNA in
      these cells increased with osteoblast phenotypic development. We also determined
      that the response could be mimicked by combining the effect of 8-bromo-cAMP and
      12-O-tetradecanoyl-phorbol-13-acetate, stimulators of the protein kinase A and
      protein kinase C pathways, respectively, both known to be activated by PTH. The
      binding of nuclear factors to two regions previously reported to be important for
      PTH induction of the gene in UMR 106-01 cells was also examined. These data
      indicated that the binding of nuclear factors to oligonucleotides encompassing
      the TRE (-51) or the PEA3 (-80) elements changed with development of the
      osteoblast phenotype. The latter was also shown to be PTH responsive.

PMID- 10963043
TI  - Role of dopamine in malignant tumor growth.
AB  - The regulatory role of dopamine, a monoamine neurotransmitter and/or a
      neurohormone in controlling the secretion of several anterior pituitary hormones,
      cardiovascular, and renal functions, has already been extensively used by
      clinicians for therapeutic purposes. In addition to these important functions of
      dopamine, some recent reports also indicate its novel role in regulating
      malignant cell proliferation and controlling immune functions in tumor-bearing
      animals. Therefore, in this article, we discuss all the relevant information
      correlating dopamine and malignant tumor growth in order to understand the host
      tumor relationship at the level of a neurotransmitter and/or a neurohormone.

PMID- 10963044
TI  - Estrogen receptor variants in epithelial compartment of normal human breast.
AB  - Estrogen receptor (ER) splice variants have previously been identified in normal
      human breast. Normal breast, however, comprises many cell types including fat
      cells, fibroblasts, endothelial cells, and a variety of inflammatory cells
      besides breast epithelial cells. The objective of our study was to demonstrate
      the existence of several variants in the epithelial compartment of the normal
      human breast. To this end, highly enriched breast epithelial cells from reduction
      mammoplasty specimens were isolated using Percoll gradient centrifugation. We
      analyzed the presence of both wild-type (WT) and variant receptors in human
      breast epithelial cells using the seminested polymerase chain reaction and direct
      automated sequencing of the amplified products. We demonstrated that a number of
      spliced variants of the ER coexist with the WT receptor. Variants lacking exons
      2, 4, 5, and 7 are detected in the breast epithelial compartment of the normal
      human breast.

PMID- 10963045
TI  - Estrogens modulate the inhibitory effect of tumor necrosis factor-alpha on
      anterior pituitary cell proliferation and prolactin release.
AB  - Considering that tumor necrosis factor-alpha (TNF-alpha) is involved in normal
      tissue homeostasis and that its receptors are expressed in the anterior
      pituitary, we examined the effect of this cytokine on pituitary cell growth.
      Because anterior pituitary function depends on hormonal environment, we also
      investigated the influence of gonadal steroids in the effects of TNF-alpha on
      cell proliferation and the release of PRL from anterior pituitary cells. In
      addition, the release of TNF-alpha and its action on the release of PRL from
      anterior pituitary cells of rats at different stages of the estrous cycle was
      evaluated. In minimum essential medium D-valine, a medium that restricts
      fibroblastic proliferation, TNF-alpha (10 and 50 ng/mL) reduced 3H-Thymidine
      incorporation, DNA content, and active cell number. TNF-alpha failed to affect
      proliferation of cells from ovariectomized (OVX) rats. However, it significantly
      inhibited growth of cells from OVX rats cultured with 17beta-estradiol (E2) (10(
      9) M) and from chronically estrogenized rats. TNF-alpha decreased the release of
      PRL from cells of intact rats, especially in proestrous, OVX rats cultured with
      E2 and chronically estrogenized rats. The release of anterior pituitary TNF-alpha
      was higher in proestrous rats. These results indicate that TNF-alpha plays an
      inhibitory role in anterior pituitary cell growth and the release of PRL in an
      estrogen-dependent manner.

PMID- 10963047
TI  - Increased expression of growth hormone and prolactin receptors in hepatocellular
      carcinomas.
AB  - The liver is an essential target tissue for growth hormone (GH) and prolactin
      (PRL). The aim of this study was to determine the in situ expression of growth
      hormone receptor (GHR) and prolactin receptor (PRLR) in hepatocellular carcinomas
      and to compare the results with normal liver. For this purpose, in situ
      hybridization (ISH) and immunohistochemical techniques were performed and several
      tests were conducted to validate the results. By radioactive ISH, all the
      hepatocellular carcinomas studied showed labeling for GHR and PRLR mRNAs.
      Relative expression levels, determined by computer-assisted microdensity, were
      higher in hepatocellular carcinomas than in normal liver. Immunohistochemistry
      led us to confirm the constant expression of both receptor proteins in
      hepatocellular carcinomas and normal liver and to demonstrate their localization
      not only in the cytoplasm but also in the nucleus. These results confirm that the
      liver is a major GH and PRL target tissue and suggest that in hepatocellular
      carcinomas the proliferative effects of these hormones may be increased by a
      higher expression of their receptors.

PMID- 10963046
TI  - Stimulation of mitogen-activated protein kinase pathway in rat somatotrophs by
      growth hormone-releasing hormone.
AB  - Growth hormone-releasing hormone (GHRH) is an important regulator of somatotroph
      development and function. However, GHRH signaling is still not completely
      understood. Signaling through the mitogen-activated protein kinase (MAPK) pathway
      has been observed in a wide variety of cell types but has not been explored as a
      mediator of GHRH action. In this study, we examined the phosphorylation of MAPK
      pathway intermediates in response to GHRH. After treatment of the GH4 rat
      somatotroph cell line with rGHRH (10(7) M) for 2.5 min, there was robust
      phosphorylation of MAPK not seen in vehicle-treated cells. Treatment of HeLa
      cells with GHRH resulted in no activation of MAPK, but activation was conferred
      by transfection with the GHRH receptor cDNA. MAPK activation by GHRH was dose
      dependent from 1 to 100 nM, was evident at 2.5 min, peaked at 5 min, and returned
      to baseline by 20 min. Pretreatment of GH4 cells with somatostatin analog
      BIM23014 or the MEK1 inhibitor PD98095 prevented the activation of MAPK. Finally,
      treatment with GHRH increased GH4 proliferation in culture, and this response was
      prevented by pretreatment with BIM23014 and PD98095. These results indicate that
      GHRH activates the MAPK pathway. Furthermore, activation of MAPK may mediate, at
      least in part, the effects of GHRH on somatotroph cell line proliferation. The
      findings support the concept that multiple pathways mediate the effects of GHRH.

PMID- 10963048
TI  - Regulation of in vitro maturation of stimulus-secretion coupling in fetal rat
      islet beta-cells.
AB  - We have studied the maturation of a glucose-responsive insulin release from fetal
      rat islets, and specifically investigated the impact of nutrients, alpha
      adrenoceptors, imidazoline receptors, and cyclic adenosine monophosphate (cAMP).
      Islets were isolated from 21 -d-old fetal rats and maintained for 7 d in tissue
      culture at 3.3 or 11.1 mM glucose and various supplements. Culture in the
      presence of the nonglucidic nutrient alpha-ketoisocaproic acid (KIC), markedly
      enhanced both basal and stimulated insulin release from islets cultured at either
      low or high glucose. Additionally, KIC significantly elevated the insulin content
      of islets maintained in low glucose, whereas it slightly lowered it in islets
      cultured at high glucose. Culture with phentolamine, an antagonist of alpha
      adrenergic and imidazoline receptors, markedly amplified both basal and glucose
      stimulated insulin secretion when added with islets cultured in either low or
      high glucose. By contrast, the pure alpha2-adrenoceptor antagonist benextramine
      had no such effects. Addition to culture media of a membrane-permeant agonist (Sp
      cAMP[S]) or antagonist (Rp-cAMP[S]) of cAMP-dependent protein kinases types I and
      II failed to influence basal or glucose-responsive insulin secretory rates at
      either glucose concentration during culture as well as islet insulin content. In
      conclusion, islet beta-cell differentiation and functional maturation of the
      stimulus-secretion coupling can be accelerated in vitro in fetal rat pancreatic
      tissue by nutrient stimulation, and by interference with imidazoline receptors,
      whereas cAMP seems virtually ineffective in this respect. These effectors may be
      of regulatory significance in the in vivo development of glucose-sensitive beta
      cells.

PMID- 10963050
TI  - Myristoylated alanine-rich C kinase substrate protein and mRNA in bovine corpus
      luteum during the estrous cycle.
AB  - The bovine corpus luteum contains a myristoylated alanine-rich C kinase substrate
      (MARCKS) protein known to crosslink actin filaments in the cytoskeletal cortex
      associated with the plasma membrane. We conducted experiments to determine
      whether concentrations of MARCKS mRNA and protein in the bovine corpus luteum
      varied during the estrous cycle. Using Northern blots probed with a MARCKS cDNA,
      we found that luteal concentrations of MARCKS mRNA were greatest on d 4, 8, and
      12 and markedly reduced on d 16 of the cycle (p < 0.08). Similarly, Western blot
      analysis of luteal proteins revealed that concentrations of MARCKS protein were
      greatest on d 8 and least on d 16 of the cycle (p < 0.01). Exposure of slices
      from a d 8 corpus luteum to prostaglandin F2alpha (PGF2alpha) during a 10-min
      incubation in the presence of [32P]-ortho-phosphate resulted in enhanced
      phosphorylation of MARCKS in membrane and cytosolic fractions compared to that of
      controls. We therefore concluded that expression of the luteal MARCKS protein
      gene may be regulated and that PGF2alpha-induced phosphorylation of this protein
      is attributable to activation of protein kinase C.

PMID- 10963049
TI  - Effects of immobilization stress on estrogen-induced surges of luteinizing
      hormone and prolactin in ovariectomized rats.
AB  - Reproductive function has been known to be impaired by various kinds of physical
      and emotional stress, but the mechanism by which stress impairs the reproductive
      axis has not been clearly understood. In the present study, the effects of
      immobilization stress were studied on the surges of luteinizing hormone (LH) and
      prolactin (PRL) induced by 17beta-estradiol (E2) in ovariectomized rats. Two
      weeks after bilateral ovariectomy, animals were implanted with the capsule
      containing E2 or vehicle at 1000 h (designated as d 0). Immobilization was
      started at 1000 h and continued to 2100 h on d 2. Blood samples were collected
      according to the time schedule by a jugular vein catheter procedure.
      Immobilization stress inhibited basal release of LH and abolished E2-induced LH
      and PRL surges in ovariectomized (OVX) rats. Daily repeated immobilization (from
      1200 h to 1800 h, 6 h/d) for 3 d also abolished LH and PRL surges when examined
      at 1800 h on d 2. Although daily repeated immobilization stress reduced E2
      induced PRL mRNA levels, this stress failed to change LHbeta mRNA levels in the
      anterior pituitary as determined by Northern blot analysis. Gonadotropin
      releasing hormone (GnRH) receptor mRNA levels in the anterior pituitary were
      lowered by immobilization stress in the OVX, E2-treated group. Dopamine D2
      receptor mRNA levels in the anterior pituitary of OVX, E2-treated rats were
      significantly decreased at 1800 h, compared with those at 1000 h. However,
      immobilization prevented a decrease in dopamine D2 receptor mRNA levels at 1800
      h. GnRH content was increased in the mediobasal hypothalamus by immobilization in
      the OVX, E2-treated group, suggesting that GnRH release was inhibited.
      Interestingly, GnRH mRNA levels in the preoptic area-anterior hypothalamic area
      were suppressed by immobilization stress in OVX, E2-treated rats when determined
      at 1800 h. Therefore, we concluded that immobilization stress blocks E2-induced
      LH surge possibly by inhibiting synthesis and release of GnRH at the hypothalamic
      level, and an increase of dopaminergic activity via D2 receptor at the pituitary
      level might be involved in the stress blockage of E2-induced PRL surge.

PMID- 10963051
TI  - Effect of disrupting cell contact on the nuclear accumulation of beta-catenin and
      subsequent apoptosis of rat ovarian surface epithelial cells in vitro.
AB  - The present studies were designed to determine how disrupting cell contact
      induces rat ovarian surface epithelial cells (i.e., ROSE-179 cells) to undergo
      apoptosis. In the first series of studies, the effect of depleting serum and
      calcium on the levels of the adhesion proteins N-cadherin and beta-catenin was
      examined. These studies revealed that the depletion of serum and calcium results
      in the degradation of N-cadherin but not beta-catenin. However, the localization
      of beta-catenin changed from principally the plasma membrane to the nucleus. The
      nuclear localization of beta-catenin was demonstrated by Western blot and
      confocal microscopy. A second series of studies demonstrated that cells that lost
      contact in response to the depletion of serum and calcium showed enhanced beta
      catenin-dependent transcription. Finally, forced expression of a stable form of
      beta-catenin resulted in an increase in beta-catenin within the cytoplasm of
      transfected ROSE-179 cells. When these beta-catenin transfected ROSE-179 cells
      were deprived of serum and calcium, beta-catenin accumulated within the nucleus
      and accelerated the rate at which these cells became apoptotic. These data
      indicate that in viable cells, beta-catenin is part of the adhesion complex that
      maintains cell contact. If calcium-dependent cell contacts are broken, beta
      catenin accumulates within the nucleus, where it promotes transcription and
      ultimately the apoptotic death of ROSE-179 cells.

PMID- 10963052
TI  - Hepatocyte growth factor disrupts cell contact and stimulates an increase in type
      3 inositol triphosphate receptor expression, intracellular calcium levels, and
      apoptosis of rat ovarian surface epithelial cells.
AB  - The present studies revealed that hepatocyte growth factor (HGF) disrupts cell
      contact, increases both type 3 IP3 receptor and intracellular calcium ([Ca2+]i)
      levels and induces apoptosis of rat ovarian surface epithelial cells (ROSE-179
      cells). Type 3 IP3 receptor was only increased in cells that lost cell contact.
      Disrupting cell contact by depleting extracellular calcium (Ca2+) also resulted
      in an increase in [Ca2+]i levels and an increase in apoptosis. These responses
      were prevented by the addition of 0.7 mM Ca2+. Actinomycin D and cycloheximide
      prevented apoptosis that resulted from Ca2+ removal. In situ hybridization
      studies revealed that type 3 IP3 receptor was expressed at relatively low levels
      by ROSE-179 cells cultured with Ca2+ but at high levels in the absence of Ca2+.
      ROSE-179 cells cultured in Ca2+-free medium with type 3 IP3 receptor antisense
      oligonucleotide lost cell contact but did not show an increase in either type 3
      IP3 receptor protein, [Ca2+]i, or apoptosis. The nonsense oligonucleotide did not
      alter these responses to Ca2+ removal. Thus, the disruption of cell contact by
      either HGF or Ca2+ depletion increases the expression of type 3 IP3 receptor,
      which causes an increase in [Ca2+]i and the apoptotic death of ROSE-179 cells.

PMID- 10963054
TI  - Effects of growth hormone-releasing hormone-related peptide on stem cell factor
      expression in cultured rat Sertoli cells.
AB  - The growth hormone-releasing hormone (GHRH) gene produces a precursor molecule
      that contains GHRH and a carboxyl-terminal peptide that we have named GHRH
      related peptide (GHRH-RP). This peptide, like GHRH, stimulates the expression of
      stem cell factor (SCF), an important reproductive and hematopoietic cytokine, in
      vitro and in vivo. In the present study, using primary cultures of rat Sertoli
      cells, we compared the time course of action and the level of SCF stimulation
      seen following treatment with GHRH-RP and GHRH. Additionally, we investigated the
      activity of a truncated peptide, p75-92NH2, whose sequence is contained within
      GHRH-RP. All three of these peptides were shown to stimulate the steady-state
      levels of SCF mRNA to a comparable degree. However, the time course of action for
      GHRH-RP differed markedly from that of GHRH. GHRH-RP and p75-92NH2, similar to
      GHRH, induce SCF expression, at least in part, via the activation of the protein
      kinase A/cyclic adenosine monophosphate intracellular signaling pathway.

PMID- 10963055
TI  - Uptake of tritiated glibenclamide by endocrine and exocrine pancreas.
AB  - Tritiated glibenclamide binds to specific receptors and is internalized in
      pancreatic insulin-producing B-cells. We investigated, therefore, whether
      tritiated glibenclamide could be used to preferentially label the endocrine, as
      distinct from exocrine, pancreas. In isolated rat pancreatic islets, the net
      uptake of 3H-glibenclamide reached within 30 min of incubation a near-equilibrium
      value, corresponding to an apparent distribution space close to three to four
      times the islet volume. In pieces of pancreas exposed up to 1 h to 3H
      glibenclamide, however, its apparent distribution space progressively increased
      and, even at the min 60 of incubation, did not exceed a third of the wet weight
      of the pieces. Yet, no significant difference could be detected between the time
      course for 3H-glibenclamide uptake by pancreatic pieces from either control
      animals or rats injected with streptozotocin a few days before the experiments.
      Likewise, no significant difference in the paired ratio between the radioactive
      content of the pancreas and plasma could be found between the control and
      diabetic rats when examined 1, 5, or 24 h after the IV administration of 3H
      glibenclamide. These findings indicate that the sulfonylurea does not represent a
      suitable tool for preferential labeling of the endocrine pancreas in the
      perspective of its imaging by a noninvasive procedure.

PMID- 10963053
TI  - Putative role of the phosphatidylinositol 3-kinase-Akt signaling pathway in the
      survival of granulosa cells.
AB  - Insulin-like growth factor-I (IGF-I) is an important differentiation and survival
      factor for granulosa cells. The purpose of this study was to test the hypothesis
      that IGF-I promotes survival of porcine granulosa cells by signaling through the
      phosphatidylinositol (PI) 3-kinase/Akt signal transduction pathway. Treatment
      with IGF-I (100 ng/mL) for 10 min stimulated PI 3-kinase and Akt protein kinase
      activity. IGF-I stimulated the phosphorylation and activation of Akt in a time-
      and concentration-dependent manner. The PI 3-kinase inhibitors wortmannin and
      LY294002 blocked IGF-I induced increases in PI 3-kinase activity and
      phosphorylation of Akt. Additionally, IGF-I treatment prevented apoptosis. The
      survival response to IGF-I was blocked by treatment with either wortmannin or
      LY294002. These data suggest that IGF-I-induced phosphorylation of Akt is
      mediated through PI 3-kinase and that inactivation of this pathway results in
      granulosa cell apoptosis. We conclude that the PI 3-kinase/Akt signaling serves
      as a functional survival pathway in the ovary.

PMID- 10963057
TI  - In vitro metabolism of human and salmon calcitonins in rat liver and kidney
      evaluated by liquid chromatography-tandem mass spectrometry.
AB  - 1. Using LC-MS and LC-MS/MS, an in vitro study was conducted on the metabolism of
      human calcitonin (hCT) and salmon calcitonin (sCT) in rat liver and kidney to
      determine the rates of metabolism and the positions of hydrolytic cleavage in
      both peptides. 2. In lysosomal fractions of rat liver and kidney, hCT was
      degraded 9-12 times faster than sCT. Many metabolites of hCT were produced in the
      lysosomal fractions, whereas the metabolites of sCT were scarcely found. 3. In
      the case of the cytosolic fractions, three positions of initial endoproteolytic
      cleavage were found in hCT, leading to the production of many peptide fragments
      via subsequent exoproteolytic metabolism. The initial cleavage position of sCT
      could not be identified precisely, but it was postulated that the rate
      determining step in the metabolism of sCT is the endoproteolytic hydrolysis. 4.
      The studies using pure proteases and protease inhibitors indicated that the
      metabolism of calcitonins proceeds by initial endoproteolytic cleavage and
      subsequent exoproteolytic digestion, catalysed by an aspartate-protease in
      lysosomes and by a metalloprotease and cysteine-protease in combination in the
      cytosol. 5. The result suggested that the higher in vivo pharmacological activity
      of sCT compared with that of hCT may be due to a slower metabolism of the former.

PMID- 10963058
TI  - Metabolic activity of fresh and cryopreserved cynomolgus monkey (Macaca
      fascicularis) hepatocytes.
AB  - 1. The effect of cryopreservation on the metabolic capacity of monkey hepatocytes
      over 4 h in suspension and 24 h in culture was determined. Hepatocytes were
      diluted in a buffer containing 10% DMSO and frozen in a computer-controlled
      chamber. 2. Initial ethoxyresorufin and ethoxycoumarin O-deethylase (ECOD)
      activities were the same in fresh and cryopreserved (CP) hepatocytes. ECOD
      activity in suspensions declined over 4 h but was the same in fresh and CP
      hepatocytes. 3. The formation of testosterone hydroxy (OHT) metabolites (namely
      6beta-OHT, 2beta-OHT, 16beta-OHT, 16alpha-OHT, 15beta-OHT, 2alpha-OHT and 6beta
      OHT) was unaffected by cryopreservation. The loss of OHT activities over 4 h in
      CP and fresh whole cell suspensions was attributed to a loss of cofactor. CP
      hepatocyte cultures had equivalent OHT activities to freshly isolated
      hepatocytes. 4. Initial UDP-glucuronyltransferase (UGT) activities, using the
      substrates 4-methylumbelliferone, ethoxycoumarin and hydroxycoumarin, were
      equivalent in fresh and CP whole hepatocytes. At later times, UGT activity was
      lower in CP than fresh hepatocytes but this was due to a loss of UDPGA. Initial
      sulphotransferase (SULT) activities, using the substrates 2-naphthol,
      ethoxycoumarin and hydroxycoumarin, were equivalent in fresh and CP hepatocytes.
      SULT activities were less stable than UGT activities but were the same in fresh
      and CP hepatocytes throughout the 4-h incubation. 5. Initial glutathione S
      transferase activities (using 1-chloro-2,4-dinitrobenzene) were the same in fresh
      and CP hepatocytes and both did not decrease over 4 h. 6. CP monkey hepatocytes
      are a useful model for metabolic and cytotoxicity studies. These cells can be can
      be used either in suspension or in culture.

PMID- 10963056
TI  - Immunoneutralization of prolactin prevents stimulatory feedback of prolactin on
      hypothalamic neuroendocrine dopaminergic neurons.
AB  - We have found that exogenous prolactin (PRL) stimulates all three populations of
      hypothalamic neuroendocrine dopaminergic neurons. In this study, we investigated
      the effects of immunoneutralization of endogenous PRL on the activity of these
      neurons. Injection of 17beta-estradiol (E2) (20 microg subcutaneously) 10 d after
      ovariectomy induced a proestrus-like increase in PRL in peripheral plasma the
      following afternoon. At 1000 h the day after E2 injection, rats received either
      rabbit antirat PRL antiserum (PRL-AS) (200 microL) or normal rabbit serum (NRS,
      200 microL, controls) intraperitoneally. Groups of rats were then decapitated
      every 2 h from 1100 h to 2100 h. Trunk blood was collected and serum extracted
      with protein A to remove the PRL-AS/PRL complex, and the remaining free PRL was
      measured by radioimmunoassay. Sites of neuroendocrine dopaminergic nerve
      terminals, the median eminence (ME), and intermediate and neural lobes of the
      pituitary gland were excised and stored for determination of dopamine (DA) and
      3,4-dihydroxyphenyl acetic acid (DOPAC) concentrations by high-performance liquid
      chromatography electrochemical detection (EC). In addition, the anterior lobe of
      the pituitary gland, the locus of DA action, was collected. The concentration of
      PRL in NRS-treated animals increased by 1500 h, peaked by 1700 h, and returned to
      low levels by 2100 h. PRL-AS prevented the increase in PRL secretion in response
      to E2. The turnover of DA (DOPAC:DA ratio; an index of dopaminergic neuronal
      activity) in the ME of NRS-treated animals increased at 1500 h and rapidly
      returned to basal levels. Treatment with PRL-AS prevented the increase in DA
      turnover in the ME. DA turnover in the intermediate lobe increased coincident
      with the peak of PRL in serum of NRS-treated rats. PRL-AS administration
      prevented increased DA turnover in the intermediate lobe. The turnover of DA in
      the neural lobe increased by 1300 h and decreased steadily through 2100 h.
      However, administration of PRL-AS minimally suppressed the turnover of DA in the
      neural lobe. Moreover, administration of PRL-AS attenuated the rise of DA in the
      anterior lobe associated with the waning phase of the E2-induced PRL surge. These
      results clearly indicate that endogenous PRL regulates its own secretion by
      activating hypothalamic neuroendocrine dopaminergic neurons.

PMID- 10963059
TI  - Concurrent induction of rat hepatic microsomal cytochrome P450 and haem oxygenase
      by 2,2'-dipyridyl ketone: comparison with the effect of 2,2'-dipyridyl amine.
AB  - 1. The effect of 2,2'-dipyridyl ketone and 2,2'-dipyridyl amine on the induction
      of hepatic microsomal cytochrome P450 (P450) and heme oxygenase was compared, and
      their effects on five different P450 isoforms (P4501A1, 3A2, 2B1, 2E1 and 2C11)
      in rat were examined. 2. Treatment of rat with 2,2'-dipyridyL amine resulted in
      the marked induction of haem oxygenase to about seven-fold of the controls with a
      decrease in p450 content. 2,2'-Dipyridyl ketone produced concomitant induction of
      both P450 and haem oxygenase activity in a dose- and time-dependent manner
      without showing any sex differences. 3. Immunoblot analysis revealed that 2,2'
      dipyridyl ketone slightly increased CYP2E1 and CYP3A2 at low doses, but not at
      high dose levels. There was no effect on P4502C11. P4502B1 was induced by the
      treatment with 2,2'-dipyridyl ketone in a dose-dependent manner. 4. These results
      indicate that dipyridyl compounds having different bridges between two aromatic
      moieties act as differential inducers of hepatic microsomal P450s and haem
      oxygenase.

PMID- 10963060
TI  - Comparison of receptor-mediated endocytosis kinetics between wild-type t-PA and
      recombinant pamiteplase in isolated rat hepatocytes and liver cell plasma
      membranes.
AB  - 1. Differences in receptor-mediated endocytosis kinetics between pamiteplase, an
      engineered t-PA, and an unmodified rt-PA were examined using liver cell plasma
      membranes and isolated rat hepatocytes. 2. Whereas the binding site of
      pamiteplase on hepatocytes was the same as that of rt-PA, the Kd of pamiteplase
      was 5.1-7.7 times larger than that of rt-PA, indicating a lower affinity of
      pamiteplase for the t-PA receptor. 3. ke for pamiteplase measured using
      parenchymal cells or non-parenchymal cells was slightly smaller than that for rt
      PA, whereas kon for pamiteplase were much lower than that of rt-PA, suggesting
      that the interaction between pamiteplase and the receptor is slower than that of
      rt-PA because of its structural modification. 4. Therefore, the difference in
      drug disposition between pamiteplase and rt-PA is mainly due to the difference in
      the hepatic clearance caused by a change in the interaction rate between the
      ligand and its cell-surface receptor.

PMID- 10963061
TI  - Intestinal absorption and excretion of troglitazone sulphate, a major biliary
      metabolite of troglitazone.
AB  - 1. Deconjugation by sulphate transfer and intestinal absorption of troglitazone
      sulphate (M1), the major metabolite of a thiazolidinedione antidiabetic drug,
      troglitazone, were studied in the male F344 rat using 14C-troglitazone, 4C-M1 and
      35S-M1. 2. Some part of M1, produced in the liver and excreted mostly in the
      bile, was deconjugated in the intestine to the parent compound, troglitazone, by
      arylsulphate sulphotransferase originated from intestinal flora. However,
      deconjugation of M1 was not catalyzed by arylsulphatases. Caecal injection of M1
      led to the appearance of troglitazone and M1 in plasma. 3. Biliary excretion
      mostly as M1, and, following absorption, as M1 and troglitazone after
      deconjugation, were indicated as the basis for the enterohepatic circulation of
      troglitazone. 4. Enterohepatic circulation may prolong the pharmacological
      effects of troglitazone.

PMID- 10963062
TI  - Investigation of the metabolism of 14C/13C-practolol in rat using directly
      coupled radio-HPLC-NMR-MS.
AB  - 1. The metabolic fate of 14C/13C-practolol was investigated using on-line HPLC
      NMR-MS following oral administration to rat. The major route of elimination for
      the radiolabel was via the urine with the principal biotransformation products
      confirmed as the 2-hydroxy- and 2-hydroxyglucronide metabolites. 2. In addition,
      futile deacetylation, determined by the replacement of 13C-labelled acetyl groups
      with endogenous 12C-acetyls accounted for approximately 7-10% of the urinary
      metabolites, corresponding to approximately 5% of the dose undergoing N
      deacetylation. 3. Evidence for chiral metabolism was sought via NMR of isolated
      metabolites using beta-cyclodextrin as a chiral shift agent. Practolol was
      excreted as a racemate. However, some enantioselective metabolism/excretion had
      occurred as the hydroxy- and hydroxyglucuronide were not excreted as racemic
      mixtures. 4. Directly coupled radio-HPLC-NMR-MS is extremely effective for the
      identification of the metabolites of radiolabelled xenobiotics in urine samples.

PMID- 10963063
TI  - Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog,
      cynomolgus monkey and rhesus monkey.
AB  - 1. The metabolism and excretion of celecoxib, a specific cyclooxygenase 2 (COX-2)
      inhibitor, was investigated in mouse, rabbit, the EM (extensive) and PM (poor
      metabolizer) dog, and rhesus and cynomolgus monkey. 2. Some sex and species
      differences were evident in the disposition of celecoxib. After intravenous
      (i.v.) administration of [14C]celecoxib, the major route of excretion of
      radioactivity in all species studied was via the faeces: EM dog (80.0%), PM dog
      (83.4%), cynomolgus monkey (63.5%), rhesus monkey (83.1%). After oral
      administration, faeces were the primary route of excretion in rabbit (72.2%) and
      the male mouse (71.1%), with the remainder of the dose excreted in the urine.
      After oral administration of [14C]celecoxib to the female mouse, radioactivity
      was eliminated equally in urine (45.7%) and faeces (46.7%). 3. Biotransformation
      of celecoxib occurs primarily by oxidation of the aromatic methyl group to form a
      hydroxymethyl metabolite, which is further oxidized to the carboxylic acid
      analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a
      glucuronide conjugate of the carboxylic acid metabolite was produced by rabbit.
      5. The major excretion product in urine and faeces of mouse, rabbit, dog and
      monkey was the carboxylic acid metabolite of celecoxib.

PMID- 10963064
TI  - Prevention: additional thoughts.

PMID- 10963065
TI  - Health care social work treatment of patient and family emotion: a synthesis and
      comparison across patient populations and practice settings.
AB  - Health care practitioners and researchers alike are beginning to acknowledge the
      importance of emotion in health. Nevertheless, health care social workers
      continue to assume most of the responsibility for actually dealing with the
      emotions of patients and families. Literature exploring social work interventions
      with emotion are restricted to a single patient population and practice setting.
      This study conducted a content analysis of pertinent literature, systematically
      codifying strategies across patient populations and practice settings according
      to a pragmatic conceptual foundation of the professional emotion treatment
      process. Analysis yielded a comprehensive conceptually clustered matrix of 45
      strategies, establishing an objective and systematic basis for identifying and
      understanding this professional emotion treatment process for social work
      educators, practitioners, and researchers alike.

PMID- 10963066
TI  - Ethical dilemmas in general hospitals: differential perceptions of direct
      practitioners and directors of social services.
AB  - Two distinct groups of social workers in general hospitals, fourteen directors of
      social work services and eighteen direct practitioners, were interviewed
      concerning their perception, ranking and resolution patterns of ethical dilemmas.
      The reverse order of importance and somewhat different content of ethical
      dilemmas identified by the two groups reflect their differential position in the
      hierarchy of hospitals and the difference in their experience in dealing with
      ethical dilemmas vis-a-vis clients. The directors tended to depend more on
      internal loci of authority, and were far more concerned with how to interpret and
      apply the relevant laws than the direct practitioners. Their decision making
      patterns seemed to be more virtues focused in contrast to the utilitarian and
      rights based focus of the direct practitioners. The findings emphasize the need
      for social workers' knowledge of ethical theories, rules and principles, and
      ethical self-knowledge. They also point out the need for written protocols of
      debates and/or detailed descriptions of applications of ethical decision making
      models to case situations in practice. The latter may provide guidelines for
      social workers in similar situations in the future, and at the same time be used
      as material for teaching and supervision.

PMID- 10963067
TI  - The experience of women in unsuccessful infertility treatment: what do patients
      need when medical intervention fails?
AB  - Approximately half of the women who seek medical treatment for infertility never
      give birth to a child. Extended infertility treatment extracts a particularly
      devastating toll on female patients. The inability to bear children creates a
      developmental crisis for a woman, disrupting her identity, her relationships, and
      her sense of meaning. Infertility treatment tends to be delivered in an
      impersonal way, with little attention to the psychosocial needs of patients.
      Social workers can play a key role in preventive and clinical intervention, and
      can educate medical professionals about the needs of their patients when
      treatment fails. The author presents interview data from a recent study in order
      to illustrate these needs, offering guidelines for social workers and medical
      professionals.

PMID- 10963068
TI  - Psychological and social preparation for bone marrow transplantation.
AB  - Bone marrow transplantation (BMT) is a treatment for some malignant conditions
      which is considered both physically and psychologically demanding. This paper
      considers the impact of an intervention aimed at encouraging patients to be more
      involved in their own transplant preparation. A social research design was used
      to explore the psychosocial impact of BMT. Qualitative and quantitative data
      collection methods were used to survey 25 intervention-group and 229 comparison
      group respondents. After controlling for identified confounding factors,
      comparisons were made between these groups. Contrary to expectation, no
      statistically significant differences were observed between the two groups on the
      outcome measures. However, when matched for categorical confounding factors, the
      intervention group had statistically significant improvement on "preparation,"
      "post-transplant problems" and "anxiety" measures. The intervention group were
      also found to have higher scores on the "helplessness" and "fatalism" scales. The
      qualitative analyses suggest that this may have been due to a combination of
      raised expectations and non-encouraging hospital staff. Factors contributing to
      poor post-transplant adjustment were identified, as well as less problematic
      experiences common to the majority of transplant patients.

PMID- 10963069
TI  - Ecological factors associated with adolescent sexual activity.
AB  - Bronfenbrenner's (1979) ecological systems theory was used as an organizing
      framework for the research on teenage sexual activity. Per Bronfenbrenner's
      theory, the literature is discussed according to macrolevel (system-wide),
      mesolevel (immediate social environment), and microlevel (individual) factors
      that are associated with adolescent sexual involvement. Following the review,
      implications for social work are explored.

PMID- 10963070
TI  - Thalidomide: a comeback?
AB  - Thalidomide, a synthetic glutamic acid derivative first marketed in 1954 as a
      sedative, rapidly gained worldwide notoriety as a cause of phocomelia. To prevent
      further cases of this severe birth defect, thalidomide was removed from the
      market. Over the last few years, however, thalidomide has been found to exhibit
      properties of potential usefulness in a range of conditions. Trials are under way
      in rheumatic diseases, and safer analogs have been developed.

PMID- 10963071
TI  - Evaluation of spa therapy in rheumatology.

PMID- 10963072
TI  - Hematological malignancies and the bone (myeloma excluded).
AB  - Bone involvement is a rare event in lymphomas, except in patients with adult T
      cell leukemia/lymphoma associated with HTLVI. It is usually characterised by
      lytic bone lesions located in the metaphysis of long bones or in the axial
      skeleton. The occurrence of bone lesions reflects a progression of the disease
      affecting the prognosis that is related to lymphoma histologic features and
      staging. Bone lesions may occur in some lymphoproliferative disorders such as LLC
      or Waldenstrom's disease, or in myeloproliferative disorders. They may reflect a
      progression to a more aggressive disorder with a worse prognosis. The treatment
      of hematologic malignancies presenting with bone lesions and/or hypercalcemia is
      similar to the treatment of the systemic disease. In primary lymphomas of bone
      presenting with an isolated bone lesion, local treatment with radiation therapy
      and/or surgical ablation is required, and adjuvant chemotherapy may improve the
      prognosis of these located lymphomas. Glucocorticoid therapy and bisphosphonates
      are effective in treating associated hypercalcemia. Except for myeloma and ATL,
      the underlying mechanisms responsible for bone involvement in hematologic
      malignancies remain poorly understood. The unusual occurrence of bone lesions in
      these diseases probably implies distinct pathogenic mechanisms, but one can
      speculate that an increased expression of RANK/RANKL, the common final pathway in
      bone resorption, may be involved.

PMID- 10963073
TI  - Cervical spine manipulation and the precautionary principle.
AB  - Cervical manipulations can cause severe neurologic complications, which are both
      exceedingly rare and generally unpredictable. To meet the requirements of the
      principles of prevention and precaution, we believe the number of cervical
      manipulations should be reduced. To this end, we suggest that five
      recommendations developed by consensus be followed: unwanted effects, however
      minor, of previous manipulation should be looked for routinely and taken as
      absolute contraindications to further manipulation; a thorough physical
      examination, including a neurological evaluation, should be performed prior to
      manipulation; all known contraindications and indications should be followed;
      manipulation should be performed only by physicians experienced in this
      technique; and special caution should be exercised when performing first-line
      cervical manipulation.

PMID- 10963074
TI  - New therapeutic targets in rheumatoid arthritis.
AB  - Gene therapy has the significant advantage of providing targeted and continuous
      administration of a therapeutic agent within the joint. A number of targets of
      choice are discussed, including cytokines, metalloproteinase inhibitors and
      angiogenesis costimulators. Gene transfer can also be used to inhibit
      intracellular biological cascades (apoptosis, signal transduction, cell
      differentiation). Preliminary Phase I ex vivo studies have confirmed the
      feasibility of gene therapy in rheumatoid arthritis. Vectors will have to be
      improved before in vivo studies are performed.

PMID- 10963075
TI  - Fas ligand and Bax gene transcription contributes to Ro60 ribonucleoprotein
      redistribution in UV-A irradiated human keratinocytes.
AB  - OBJECTIVES: Ro ribonucleoproteins are of particular interest because they are
      serologic markers of photosensitive variants of lupus such as the subacute
      cutaneous lupus erythematosus (SCLE), in which the polycyclic skin lesions are
      triggered by exposure to the sun. We study the role of apoptosis in the
      expression of Ro antigen. METHODS: We used UV-A irradiated keratinocytes.
      RESULTS: We demonstrate in cultured human UVA-irradiated keratinocytes that the
      enhanced expression of Ro60 ribonucleoprotein is caused by antigenic
      redistribution consecutive to Fas-L and Bax gene activation.

PMID- 10963076
TI  - Analysis of TNFalpha microsatellites in 35 patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVES: Although the cause of Sjogren's syndrome remains unknown, many
      arguments suggest a role for both environmental and genetic factors. An
      association with HLA molecules has been established. Other genes on the short arm
      of chromosome 6 may be involved, most notably the TNF gene, which may be pivotal
      in the development of the epithelial lesions. METHODS: We investigated TNFalpha
      microsatellites in 35 patients with primary Sjogren's syndrome and in 146 healthy
      controls. RESULTS: The frequency of the TNFalpha10 allele showed a non
      significant increase in the Sjogren's disease group (28.6% vs 15.8%; P = NS). We
      found significant increases when we considered only those Sjogren's disease
      patients with joint manifestations (N = 24; 37.5% vs 15.7%; P < 0.05) or only
      those with anti-Ro(SSA) antibodies (N = 10; 50% vs 15.7%; P < 0.05). CONCLUSION:
      Our data support a role for the TNFalpha10 allele in primary Sjogren's syndrome,
      particularly those forms with joint symptoms and anti-Ro(SS-A) antibodies.

PMID- 10963077
TI  - Magnitude and duration of the effects of two spa therapy courses on knee and hip
      osteoarthritis: an open prospective study in 51 consecutive patients.
AB  - OBJECTIVE: To evaluate the effects of spa therapy on knee and hip osteoarthritis
      by studying patients given the same treatment on two different occasions.
      PATIENTS AND METHODS: A prospective study of two medically-supervised, 3-week spa
      therapy courses performed at an interval of about 1 year in 51 consecutive
      patients with knee and/or hip osteoarthritis, most of whom were overweight (mean
      body mass index, 30 +/- 5 kg/m2). Mean age was 66 years. Study data were
      collected over a 17-month period. RESULTS: Lequesne's algofunctional index was
      significantly improved 5 and 8 months after the first course (by 1.74 +/- 2.2, P
      < 0.0001; and by 0.89 +/- 2.4, P = 0.017; respectively) and 5 months after the
      second course (by 1.26 +/- 3, P = 0.008). Walking distance showed comparable
      improvements. The decrease in medication use was not significant. No significant
      differences were found between the effects of the two courses after 20 days and 5
      months. The advantages and drawbacks of the repeated treatment design used in
      this study are discussed. CONCLUSION: Although some sources of bias could not be
      eliminated, our data suggest that spa therapy may be effective in knee and hip
      osteoarthritis. The repeated treatment design may prove useful for evaluating
      treatments to which patients cannot be blinded.

PMID- 10963078
TI  - Subacromial impingement: influence of coracoacromial arch geometry on shoulder
      function.
AB  - OBJECTIVE: To find correlations between radiological coracoacromial arch geometry
      and shoulder function in patients with subacromial impingement syndrome. PATIENTS
      AND METHODS: During a prospective study of the efficacy of arthroscopic
      subacromial decompression, we evaluated the function of the treated and
      contralateral shoulders using Constant's functional score and confronted the
      results to several radiographic parameters reflecting coracoacromial arch
      geometry. RESULTS: Constant's score values were low (42 +/- 15) because of pain
      and a low level of activity. Males had significantly higher scores than females.
      Constant's score was unaffected (P > 0.05) by patient age, the side, the level of
      activity, or the duration of symptoms, but was significantly influenced by the
      orientation of the acromion with respect to the scapular spine and to the
      vertical scapular axis. The preoperative Constant's score was significantly
      higher in patients with a more horizontal acromion (P = 0.01). A very tight
      correlation was found between the preoperative Constant's score and the angle
      between the acromion and scapular spine (P = 0.0003). CONCLUSION: Based on our
      results, we defined an open and a closed coracoacromial arch geometry.
      Coracoacromial arch geometry is correlated with shoulder function syndrome and
      can assist in the interpretation of rotator cuff impingement.

PMID- 10963079
TI  - Ultrasound investigation of the rotator cuff after computed arthrotomography
      coupled to bursography.
AB  - OBJECTIVES: To evaluate the diagnostic performance of ultrasound rotator cuff
      imaging after injection of contrast medium into the glenohumeral joint and
      subacromial bursa. PATIENTS AND METHODS: Twenty-eight patients underwent
      ultrasonography before and after injection into the glenohumeral joint and
      subacromial bursa of a mixture of iodinated contrast medium and lidocaine
      solution. Findings were compared with those from computed tomography of the joint
      and bursa. RESULTS: Sixteen 16 (16/28, 57%) post-contrast ultrasound scans
      revealed or confirmed rotator cuff lesions. For supraspinatus and infraspinatus
      lesions, there were three false-negatives and no false-positives. Three false
      negatives were recorded for subscapularis lesions. All false-negatives occurred
      both before and after the contrast medium injections. CONCLUSION: Injecting
      contrast medium into the glenohumeral joint and subacromial bursa improves the
      diagnostic yield of rotator cuff ultrasonography. We suggest that ultrasonography
      be performed after injections of drugs into the shoulder structures, particularly
      the subacromial bursa.

PMID- 10963080
TI  - Prevalence of Paget's disease of bone and spinal hemangioma in French women older
      than 75 years: data from the EPIDOS study.
AB  - OBJECTIVE: To evaluate the prevalence in France of Paget's disease in elderly
      women. PATIENTS AND METHODS: The prevalences of Paget's disease and of thoracic
      and lumbar vertebral hemangioma were determined in a random nested cohort of 770
      women from the EPIDOS study cohort. EPIDOS is a prospective study of the risk of
      proximal femoral fracture in 7,598 female, community-dwelling volunteers older
      than 75 years of age. The EPIDOS study patients were recruited at five centers in
      France (Amiens, Lyon, Paris, Montpellier, and Toulouse). For the nested study,
      anteroposterior and lateral radiographs of the thoracic and lumbar spine were
      read by two rheumatologists and classified into four groups: no Paget's disease
      or hemangioma, possible Paget's disease or hemangioma, definite Paget's disease,
      and definite hemangioma. Radiographs in the last three groups were read by a
      rheumatology professor and a radiology professor, both independent from the
      study. RESULTS: Twenty-five patients had incomplete or poor-quality radiograph
      sets, leaving 745 patients for the study. A vertebral hemangioma was found in
      four patients (0.54%; 95% confidence interval [CI], 0.01-1.1%) and vertebral
      Paget's disease in four other patients (0.54%; 95% CI, 0.01-1.1 %). All the
      pagetic vertebrae were at the lumbar spine. Three of the four Paget's disease
      patients were unaware of the condition before their inclusion in the study. Based
      on previous estimates that thoracic and lumbar foci are present in 30 to 50% of
      Paget's disease patients, our data suggest that the overall prevalence of Paget's
      disease in French women older than 75 years may be in the 1.1-1.8% range.
      CONCLUSION: The prevalence of Paget's disease in elderly French women is similar
      to that recently reported in Britain.

PMID- 10963081
TI  - The representation of the back in idiomatic expressions--do idioms value the
      body?
AB  - OBJECTIVE: Whilst investigating the influence of patients' representations on the
      impact of teaching in the back school, we took an interest in 1) the place of the
      back in the French idioms referring to the body; and 2) the meaning these idioms
      convey about the back. METHODS: The idioms including body part terms were sought
      on the basis of a compilation of French idioms; it has to be noted that such a
      compilation, however excellent it may be, can only offer a partial view of lay
      conversation. Occurrence of body parts and of their connotations were assessed.
      Idioms were classified as positive, negative or neutral, keeping in mind the
      difficulties of a strict classification in such a field. Drawings were then
      performed on the basis of the results of the descriptive analysis. RESULTS:
      Globally, idiomatic expressions offer a rather negative picture of the body or at
      least suggest that the body is prominently used to express negative ideas and
      emotions. This is particularly striking for the idioms associated with the back.
      CONCLUSION: The analysis of idioms referring to the body allows us to 'see with
      our own eyes' another aspect of the representations of the body and the back, as
      they are conveyed in the French language.

PMID- 10963082
TI  - Do we use morphine often enough? An opinion survey in 100 rheumatology department
      patients.
AB  - PATIENTS AND METHODS: Shortly before their discharge from a rheumatology
      department, 100 patients with a mean age of 54 +/- 16 years completed a 20-item
      questionnaire on morphine therapy. Pain scale scores were 77.1 +/- 19 at
      admission and 44.2 +/- 24 at questionnaire completion. RESULTS: Thirty-three
      patients, including 27 with spinal or nerve root disorders, received morphine
      during their stay. Five of these patients had a malignancy. Among patients who
      received morphine, 21% (6/29) were disappointed with the drug. Only four of the
      patients who did not receive morphine (4%) wished they had. Thirty-six percent of
      patients (30/83) reported previous morphine therapy given by a primary care
      physician (10/30) or a specialist (14/30) and/or in a hospital (22/30). Only five
      patients (5/100, 5%) said they regretted not having received morphine for past
      pain; however, 45% (35/78) of patients agreed with the suggestion that French
      physicians do not use morphine often enough. Most patients (82%, 65/77) agreed
      that morphine can be used to treat pain due to rheumatic disorders, although 92%
      (83/90) felt that morphine should be reserved for "intolerable" pain. Only 37%
      (34/92) of the patients were apprehensive about using morphine, 57% (45/79) were
      aware of the risk of dependency, 66% (44/79) of the risk of behavioral or
      attention disorders, and 53% (41/78) of the risk of tolerance. CONCLUSION:
      Expectations of French rheumatology department patients about morphine use were
      roughly satisfactory. The mean pain scale score above which the patients felt
      morphine should be given was 70.5 +/- 20.

PMID- 10963083
TI  - Pseudotumoral osteochondromatosis of the hip in a soccer player.
AB  - The authors present a case of pseudotumoral osteochondromatosis of the hip,
      interesting for its clinical and radiological features. They discuss the
      incidence of the sport in the pathogenesis of the loose bodies and the magnetic
      resonance findings.

PMID- 10963084
TI  - Destructive hip disease complicating traumatic paraplegia.
AB  - Recent progress in the management of spinal cord injury has provided longer
      survivals, and as a result the incidence of secondary bone and joint disorders
      has increased. Joint lesions due to syringomyelia complicating a cervical spinal
      cord injury are the most common of these disorders. We report a case of
      destructive hip disease 7 years after an injury responsible for complete
      paraplegia with sensory loss. The joint lesions were painless, and there was no
      local evidence of inflammation. Hip radiographs disclosed atrophic
      osteoarthropathy with complete destruction of the femoral neck and head. This
      unusual case raises questions about the pathophysiology of neuropathic
      osteoarthropathy in paraplegics.

PMID- 10963085
TI  - Uveitis, an under-recognized adverse effect of pamidronate. Case report and
      literature review.
AB  - Ophthalmologic adverse effects of bisphosphonate therapy are infrequent and of
      unclear pathogenesis. The most common has been anterior uveitis, of which 18
      cases have been reported. Onset was within 24 to 48 hours after infusion
      initiation, and both eyes were affected in most patients. The outcome was
      favorable within a few days after bisphosphonate discontinuation and topical
      glucocorticoid therapy, although rechallenge was frequently followed by a
      recurrence. Bisphosphonates are being used successfully in an increasingly broad
      range of disorders. We report a case of pamidronate-induced anterior uveitis and
      present a review of the relevant literature.

PMID- 10963086
TI  - Osteoporotic fractures at presentation of Cushing's disease: two case reports and
      a literature review.
AB  - Osteoporosis is a common complication of Cushing's disease/syndrome. Fractures
      can be the presenting manifestation. We report two cases and review 28 others
      from the literature. Clinical, laboratory, and absorptiometry data are reviewed;
      the vertebrae and ribs were the most common fracture sites, and osteoporosis
      reversal after treatment varied with age, gender, and symptom duration. The
      pathophysiology, which remains controversial, is discussed. A search for
      Cushing's disease/syndrome should be part of the routine evaluation of
      osteoporosis in children and adults, particularly men.

PMID- 10963087
TI  - Juvenile relapsing periarteritis nodosa and streptococcal infection.
AB  - Classic polyarteritis nodosa is a multisystem inflammatory disease associated
      with necrotizing vasculitis of small and medium arteries. In most cases, the
      causes of polyarteritis nodosa remain unknown, but viruses (HBV, HCV, HIV) and
      microbes (especially streptococcus) have been considered as etiologic or
      contributing factors. A 13-year-old boy was admitted with fever, skin lesions,
      polyarthritis and muscle involvement. A muscle biopsy demonstrated a necrotizing
      vasculitis and antistreptolysin titre was tremendously increased. His condition
      improved following the administration of oral steroids but he experienced
      relapses 5 and 12 years later when penicillin withdrawal was attempted. The
      flares were accompanied by a major increase of antistreptolysin titre and
      response to corticosteroid was obtained. He is currently 38 years old and he
      remains well on prophylactic penicillin. Polyarteritis nodosa in children may
      occur after a streptococcal infection. It may be prudent to consider penicillin
      prophylaxis in patients with periarteritis nodosa when a streptococcal etiology
      is documented or highly suspected.

PMID- 10963088
TI  - A study of the specificity of antinuclear antibodies to extractable nuclear
      antigens in systemic lupus erythematosus patients in Tunisia.

PMID- 10963090
TI  - Ecosystem and ecotomo: a nature or society-nature relationship?
AB  - The notion of entorno is discussed and its mutual dependence upon the organism is
      emphasised. Both the etymology and meaning of ethos, oikos, entorno and ecotomo
      are discussed. The intimate relation between Ethology and Ecology is also shown.
      A reference background is given to explain how the commonly considered isolated
      components organism/society and entorno/nature articulate in the form of a
      relation. It is argued that the integrated concepts that originated the notion of
      ecosystem have been set aside. The term ecotomo is proposed, which refers to any
      territorial unit that, considered at a local, regional or global level, emerges
      from the society-nature relationship.

PMID- 10963089
TI  - Do adults develop transient synovitis of the hip? Three case reports.

PMID- 10963091
TI  - A mathematical model of uterine dynamics and its application to human
      parturition.
AB  - We have developed a simple mathematical model with three physiologically
      significant states to describe the changes in intrauterine pressure associated
      with a contraction during human parturition. The myometrium is modelled as a set
      of smooth muscle cells, each of which is in one of three states (quiescent,
      contracted, refractory) at a given time. These states are occupied according to a
      cycle governed by three temporal parameters. The solutions of the equations
      describing the model show an oscillatory behavior for particular values of these
      parameters, which is very similar to the time dependent development of
      intrauterine pressure during labor. Due to its non-linear terms, our model could
      lead to chaotic oscillations (in the mathematical sense), whose clinical
      counterpart may occur in cases of dystocia. Despite its simplicity, this model
      appears to be a useful guide to further investigations of the oscillatory
      behavior of the myometrium, or other smooth muscles, in normal and pathological
      situations.

PMID- 10963092
TI  - Interference competition set limits to the fundamental theorem of natural
      selection.
AB  - The relationship between Fisher's fundamental theorem of natural selection and
      the ecological environment of density regulation is examined. Using a linear
      model, it is shown that the theorem holds when density regulation is caused by
      exploitative competition and that the theorem fails with interference
      competition. In the latter case the theorem holds only at the limit of zero
      population density and/or at the limit where the competitively superior
      individuals cannot monopolize the resource. The results are discussed in relation
      to population dynamics and life history evolution, where evidence suggests that
      the level of interference competition in natural populations is so high that the
      fundamental theorem does not apply.

PMID- 10963093
TI  - Differentiation of wing epidermal scale cells in a butterfly under the lateral
      inhibition model--appearance of large cells in a polygonal pattern.
AB  - Cellular pattern formations of some epithelia are believed to be governed by the
      direct lateral inhibition rule of cell differentiation. That is, initially
      equivalent cells are all competent to differentiate, but once a cell has
      differentiated, the cell inhibits its immediate neighbors from following this
      pathway. Such a differentiation repeats until all non-inhibited cells have
      differentiated. The cellular polygonal patterns can be characterized by the
      numbers of undifferentiated cells and differentiated ones. When the
      differentiated cells become large in size, the polygonal pattern is deformed
      since more cells are needed to enclose the large cell. An actual example of such
      a cellular pattern was examined. The pupal wing epidermis of a butterfly Pieris
      rapae shows a transition of the equivalent-size cell pattern to the pattern
      involving large cells. The process of the transition was analyzed by using the
      method of weighted Voronoi tessellation that is useful for treatment of
      irregularly sized polygons. The analysis supported that the pattern transition of
      the early stage of the pupal wing epidermis is governed by the lateral inhibition
      rule. The differentiation takes place in order of largeness, but not smallness,
      of the apical polygonal area in the differentiating region of the pupal wing.

PMID- 10963094
TI  - Emergence and maintenance of sex among diploid organisms aided by assortative
      mating.
AB  - Using computer simulations I studied the simultaneous effect of variable
      environments, mutation rates, ploidy, number of loci subject to evolution and
      random and assortative mating on various reproductive systems. The simulations
      showed that mutants for sex and recombination are evolutionarily stable,
      displacing alleles for monosexuality in diploid populations mating assortatively
      under variable selection pressure. Assortative mating reduced excessive allelic
      variance induced by recombination and sex, especially among diploids. Results
      suggest a novel adaptive value for sex and recombination. They show that the
      adaptive value of diploidy and that of the segregation of sexes is different to
      that of sex and recombination. The results suggest that the emergence of sex had
      to be preceded by the emergence of diploid monosexual organisms and provide an
      explanation for the emergence and maintenance of sex among diploids and for the
      scarcity of sex among haploid organisms.

PMID- 10963095
TI  - Noise-driven neocortical interaction: a simple generation mechanism for complex
      neuron spiking.
AB  - We discuss a generic scenario along which complex spiking behavior evolves in
      biologically realistic neural networks. Our nonlinear dynamics approach is based
      directly on rat neocortical in vitro recordings. Using this experimental data, we
      obtain a full overview on the possible spiking behaviors of pyramidal neurons
      that are engaged in binary interactions. Universality arguments imply that the
      observed spiking behaviors are largely independent from the specific properties
      of individual neurons; theoretical arguments and numerical experiments indicate
      that they should be observable in in vivo neocortical neuron networks.

PMID- 10963096
TI  - Systemic lupus erythematosus or Aicardi-Goutieres syndrome?

PMID- 10963097
TI  - A prognostic index as diagnostic strategy in children suspected of
      mitochondriocytopathy.
AB  - The aim of this study was to assess an optimal screening for paediatric patients
      suspected of mitochondriocytopathy to justify a muscle biopsy. Forty-five
      patients were included. Medical history, physical examination, cardiac and
      ophthalmologic evaluation, clinical chemical investigations, in vivo function
      tests, neuroimaging and a skeletal muscle biopsy were performed in all patients.
      The results of the biochemical muscle studies were compared with the results of
      the other investigations. First, parameters with a statistical relationship with
      the result in muscle, normal or deficient, were selected. Secondly, a prognostic
      index was constructed using these parameters. Five parameters were selected: age
      <4 years, elevated fasting lactate to pyruvate ratio, elevated thrombocyte count,
      elevated lactate, and elevated alanine. Each parameter was scored 0 (not present)
      or 1 (present). The chance of a normal biopsy with a given value of this index
      (sum of the scores) was calculated: logit (Pr) = alpha + beta x index; alpha: 
      0.8167 and beta: 0.8331. (Pr: probability of normal biopsy.) The chance of a
      normal biopsy with an index value of 5 is 0.03, 4 is 0.07, 3 is 0.16, 2 is 0.30,
      1 is 0.50 and 0 is 0.69. This prognostic index is a valuable instrument in
      deciding whether the suspicion of mitochondriocytopathy is strong enough to merit
      a muscle biopsy.

PMID- 10963098
TI  - Abnormal somatosensory evoked potentials indicate compressive cervical myelopathy
      in mucopolysaccharidoses.
AB  - Compressive myelopathy at the cranio-cervical junction is a complication of
      mucopolysaccharidoses (MPS). To detect cervical myelopathy we recorded median and
      posterior tibial nerve SEPs in 15 patients aged 2.4-33.4 years (median 8.8 years)
      with MPS I-S (n = 3), MPS IVA (n = 8) and MPS VI (n = 4). In addition to the
      cortical waveforms we recorded the subcortical median nerve SEPs N13b and P13
      generated near the cranio-cervical junction and the lemniscal P30 after posterior
      tibial nerve stimulation. MRI studies in 13 subjects revealed spinal cord
      compression at the cranio-cervical junction in 10 patients; 5 patients had an
      increased signal intensity on the T2-weighted initial MRI indicating high
      cervical myelomalacia and 4 patients had clinical signs of cervical myelopathy.
      We did not find a relationship between the SEPs and spinal cord compression.
      Abnormal SEPs were found in the patients with MRI evidence of myelomalacia
      (sensitivity 1.0, specificity 1.0) and correspondingly in the patients with
      clinical signs (sensitivity 1.0, specificity 0.91). The SEPs consequently
      deteriorated in 2 subjects of 7.3 and 10.3 years of age. Abnormal SEPs indicated
      subclinical cervical myelopathy in 3 subjects. Cervical cord compression may be
      present before occurrence of clinical or electrophysiological evidence of
      myelopathy. However, we feel that the SEP analysis is useful to detect functional
      impairment of the cervical cord in patients with MPS.

PMID- 10963099
TI  - MR patterns of hypoxic-ischemic brain damage after prenatal, perinatal or
      postnatal asphyxia.
AB  - The relationship between MR patterns of brain damage and type or timing of
      perinatal hypoxia-ischemia was studied. MR images of 104 children with evidence
      of bilateral posthypoxic-ischemic brain damage and neonatal records were
      reviewed. Three different MR patterns were found. Periventricular leukomalacia
      occurred in 73 children, in 82% after a history of subacute or chronic hypoxia
      ischemia, in 71% after preterm birth. Predominant lesions of basal ganglia and
      thalamus occurred in 21 children, in 95% preceded by acute profound asphyxia, in
      85% after term birth. Multicystic encephalopathy occurred in 10 infants, in 70%
      preceded by mild signs of hypoxia-ischemia, followed by an unexpectedly severe
      encephalopathy, in 60% after term birth. Statistical analysis showed that the
      patterns of injury were primarily related to the type of hypoxia-ischemia. We
      conclude that the type of hypoxia-ischemia, rather than the postconceptional age
      at occurrence determines the pattern of brain injury.

PMID- 10963100
TI  - Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset
      encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria?
AB  - Two distinct disorders with elevated urinary excretion of 2-hydroxyglutaric acid
      are known: L-2-hydroxyglutaric aciduria and D-2-hydroxyglutaric aciduria. This
      paper presents clinical and biochemical studies in three patients and
      unsuccessful prenatal diagnosis in one case with combined D-2- and L-2
      hydroxyglutaric aciduria. We suggest that these patients, who displayed a
      phenotype of neonatal onset metabolic encephalopathy, present a third variant of
      2-hydroxyglutaric aciduria. Prenatal diagnosis is not reliable in this disorder.

PMID- 10963101
TI  - A case of Hoyeraal-Hreidarsson syndrome: delayed myelination and hypoplasia of
      corpus callosum are other important signs.
AB  - We report the case of a 7-year old girl with Hoyeraal-Hreidarsson syndrome (HHS)
      and review other cases of HHS. In addition to the previously described important
      signs of HHS, i.e., prenatal growth retardation, microcephaly, psychomotor
      retardation, progressive pancytopenia, immunological abnormalities, and
      cerebellar hypoplasia and ataxia, we consider that delayed myelination of
      cerebral white matter and hypoplastic corpus callosum should be added to the list
      of important signs. However, it is not clear whether delayed myelination of white
      matter in HHS indicates dysmyelination or demyelination. Furthermore, we suggest
      that immunological abnormalities of both T and B cells are one of the important
      signs of HHS. We consider these new important signs to be valuable for the
      diagnosis of HHS.

PMID- 10963102
TI  - Swelling of the third nerve in a child with transient oculomotor paresis: a
      possible cause of ophthalmoplegic migraine.
AB  - Transient oculomotor nerve palsy is rarely observed in childhood and mostly is
      recognized to be a migraine equivalent. We report an 8-year old girl who
      presented with recurrent attacks of transient oculomotor paresis. The clinical
      profile of the patient suggested transient dysfunction in the context of an
      ophthalmoplegic migraine. A CT scan was normal, but MRI demonstrated a swollen
      right oculomotor nerve.

PMID- 10963103
TI  - Painless fractures and thermoregulation disturbances in sensory-autonomic
      neuropathy: electrophysiological abnormalities and sural nerve biopsy.
AB  - We describe the case of a young girl suffering from thermoregulation
      disturbances, painless fractures and arthropathy since early childhood. The
      patient was diagnosed as having a hereditary sensory autonomic neuropathy.
      Although needle EMG, conventional nerve conduction studies and somatosensory
      evoked potentials gave normal results, sympathetic skin responses (SSRs) were
      absent. Sural nerve biopsy showed a substantial reduction in the number of small
      myelinated and unmyelinated fibers. We emphasize the importance of SSR testing in
      revealing a condition which is otherwise difficult to identify by
      electrophysiological techniques. The combined evidence of functional and
      morphological findings is strongly suggestive of selective peripheral nerve
      involvement.

PMID- 10963104
TI  - Endovascular treatment of a giant aneurysm of the internal carotid artery in a
      child with visual loss: case report.
AB  - We report on a case of a giant aneurysm of the internal carotid artery in a 11
      year old boy presenting with gradual unilateral visual loss, combined with slight
      headache and retro-orbital pain. Endovascular balloon occlusion of the internal
      carotid artery combined with monitoring of somatosensory evoked potentials was
      performed. Follow-up MR imaging six months after balloon occlusion revealed
      complete thrombosis and considerable retraction of the aneurysm. However, visual
      loss persisted, since therapy was initiated too late and optic nerve atrophy had
      already occurred. It is important to emphasize that visual disturbance should be
      considered as an emergency, and, although rare, aneurysms do occur in the
      pediatric population.

PMID- 10963105
TI  - Familial systemic lupus erythematosus and congenital infection-like syndrome.
AB  - We present two siblings with congenital and progressive encephalopathy associated
      with systemic lupus erythematosus. The two brothers presented soon after birth
      with an encephalopathy associated with intracranial calcification (=2),
      intrauterine growth retardation (= 2), hepatitis (= 1) and thrombocytopenia (=
      1), mimicking a congenital virus infection. Within the first year of life both
      children developed hypocomplementaemia and systemic lupus erythematosus (SLE),
      the main features of which were a discoid lupus-like rash on the hands and feet
      and the progressive production of high levels of autoantibodies. Both children
      were severely handicapped and died in early childhood from streptococcal
      infections. There are many causes of congenital encephalopathy with intracranial
      calcification. The early development of systemic lupus in these children
      suggested that their cerebral disease formed part of an autoimmune process.
      Complement levels and autoantibody profiles should be considered part of the
      investigation of a child with congenital infection-like syndrome, particularly
      when there are progressive dermatological complications.

PMID- 10963107
TI  - A rare variant of Guillain-Barre syndrome with acute motor axonal neuropathy
      (AMAN) in a Caucasian boy.

PMID- 10963106
TI  - Malignant rhabdoid tumor of the brain: quantitative 1H MR-spectroscopy and
      cytogenetics.

PMID- 10963108
TI  - Mental retardation, tall stature and minor phenotypic abnormalities associated
      with a de novo complex chromosome rearrangement.

PMID- 10963109
TI  - Bcl-2 expression in colorectal tumours. Correlation with p53, mdm-2, Rb proteins
      and proliferation indices.
AB  - Immunostaining for bcl-2 protein was performed in 27 colorectal adenomas and 108
      colorectal adenocarcinomas. The aim of the study was to determine bcl-2
      expression in correlation with p53, mdm-2 and Rb expression, with proliferation
      indices (Ki-67-LI, PCNA-LI) as well as with conventional clinicopathological
      variables. A higher proportion of adenomas (30.8%) than carcinomas (16.7%)
      expressed bcl-2 and conversely, a lower proportion of adenomas (7.4%) than
      carcinomas expressed p53 (57.1%), the difference being statistically significant
      (p<0.0001). No correlation of bcl-2 expression with p53 expression (parallel or
      inverse) as well as with the other parameters studied was observed in any tumour.
      The bcl-2+/p53- subgroup of cancers showed a trend for correlation with negative
      lymph node status. Our data suggest, that bcl-2 expression may be involved in the
      early phase of colorectal carcinogenesis regardless of p53 status, while p53
      function may be involved in a late stage of the adenoma-carcinoma sequence. P53
      is apparently not involved in the regulation of apoptosis in the colorectal
      neoplasias or perhaps bcl-2 expression, as an early event in colorectal tumours,
      may occur before changes of p53 take place. Tumours with bcl-2+/p53-
      immunophenotype are frequently associated with negative lymph node status and
      seem to have a less aggressive behavior.

PMID- 10963110
TI  - Skeletal muscle abnormalities associated with occupational exposure to mercury
      vapours.
AB  - There is scarce information on the possible effects of chronic exposure to
      mercury on skeletal muscle. Dental personnel are frequently exposed to inhalation
      of metallic mercury vapours. The skeletal muscle of five technicians and one
      dentist (females, age 36-55) was studied. All of them presented symptoms of
      chronic mercury poisoning. Needle biopsy was taken from the quadriceps femoris
      muscle and samples were prepared for light microscope histochemistry and for
      transmission electron microscopy. Selective atrophy of type IIB muscle fibres was
      found in patients, and in one of them there was fibre grouping. Most of the
      muscles showed increased fibre area per capillary. Atrophy was confirmed by the
      ultrastructural study, demonstrating increase of intermyofibrillar spaces, loss
      of myofibrils or complete disappearance in some fibres, and sarcolemmal foldings.
      Splitting of the fibres was also found. Some capillaries were altered, showing
      endothelial infoldings into the lumen, thickened basement membrane and partial or
      total occlusion. The alterations found in muscle may be secondary to nerve
      damage, to ischemia caused by capillary lesion and/or to a direct effect of
      mercury on muscle fibre proteins.

PMID- 10963112
TI  - Immunohistochemical and in situ hybridization studies of choline
      acetyltransferase in large motor neurons of the human spinal cord.
AB  - The localization of choline acetyltransferase (ChAT) protein and mRNA was
      investigated in large motor neurons of the lumbar spinal cord of 10 autopsied
      individuals without neurological diseases, by immunohistochemistry and in situ
      hybridization. In the immunohistochemistry using 20 serial tissue sections with a
      total thickness of 80 microm, about approximately 58-85% (average 67%) of the
      large motor neurons (30 microm and more in somal minimal diameter) in the ventral
      horn were stained with the anti-human ChAT antibody. In the positive neurons,
      most immunoreactive products were observed focally in the perikarya.
      Occasionally, the perikarya of some neurons were stained diffusely. In situ
      hybridization with a single 4 microm-thick tissue section showed that almost all
      large motor neurons had positive signals (approximately 93-100%, average 98%),
      which were distributed diffusely in the perikarya. The positivity rate in the in
      situ hybridization was higher than that in the immunohistochemistry for all 10
      cases. These results indicate that ChAT mRNA is transcribed in almost all large
      motor neurons in the ventral horn of the human spinal cord, but ChAT protein
      cannot always be detected in the cytoplasm by immunohistochemistry.

PMID- 10963111
TI  - Changes in the immunoreactivity of substance P and calcitonin gene-related
      peptide in the laryngeal taste buds of chronically hypoxic rats.
AB  - The distribution of substance P (SP)- and calcitonin gene-related peptide (CGRP)
      immunoreactive nerve fibers in the taste buds of the epiglottis and aryepiglottic
      folds was compared between normoxic control and chronically isocapnic hypoxic
      rats (10% O2 and 3-4% CO2 for 3 months). In the normoxic laryngeal taste buds, SP
      and CGRP-immunoreactive fibers were detected within the taste buds, where they
      appeared as thin processes with many varicosities. Most CGRP fibers showed
      coexistence with SP, but a few fibers showed the immunoreactivity of CGRP only.
      The density of intra- and subgemmal SP and CGRP fibers penetrating into the
      laryngeal taste buds was significantly higher in chronically hypoxic rats than in
      normoxic control rats. Water intake in the hypoxic rats was significantly lower
      than in the normoxic rats. These results indicate that the increased density of
      SP- and CGRP-containing nerve fibers within the laryngeal taste buds is a
      predominant feature of hypoxic adaptation. The altered peptidergic innervation
      and reduced water intake support the hypothesis that the laryngeal taste buds are
      involved in water reception, and that the water reception may be under the
      control of peptidergic innervation.

PMID- 10963113
TI  - Metamorphosed fibroblasts and their relation to the histogenesis of malignant
      fibrous histiocytoma in experimental murine model.
AB  - Malignant fibrous histiocytoma (MFH) is a clinicopathologically established
      entity, but its histogenesis remains to be clarified. We have reported the
      existence of a specific cell type, the "fibrohistiocytoid (FH) cells", in various
      chronic inflammatory tissues. The FH cells are the metamorphosed fibroblasts and
      we have revealed the morphological resemblance between FH cells and MFH cells. In
      the present study we carried out some experiments to ascertain whether the FH
      cells have a possibility of neoplastic potential for the development of MFH in
      mice. A total of 50 female Balb/c mice treated with a chemical carcinogen, 9,10
      dimethyl-1,2-benzanthracene (DMBA), were examined histopathologically from 8 to
      22 weeks after the initial treatment. It was found that 1) the chemically induced
      tumors in the mice resembled human pleomorphic/ storiform variant of MFH and
      cells from the tumor were transplantable subcutaneously in the back of another
      mouse, 2) the tumors were composed mainly of malignant FH cells, and there were
      many benign FH cells and fibroblasts in granulation tissues obtained at the
      initial stage of the experiment, 3) all DNA histograms obtained from MFHs were
      aneuploid and granulation tissues were diploid, and 4) benign FH cells in the
      granulation tissue appeared to have higher DNA synthesis activity than typical
      fibroblasts on the basis of bromodeoxyuridine (BrdU) labeling and
      cytofluorometric studies. From these findings, we suggest that the FH cells are
      not only a merely morphologically changed fibroblast, but also a biologically
      ominous cell which may contribute to develop MFH in mice.

PMID- 10963114
TI  - Ethylnitrosourea (ENU)-induced apoptosis in the rat fetal tissues.
AB  - Ethylnitrosourea (ENU), a well known DNA alkylating agent, induces anomalies in
      the central nervous system (CNS), craniofacial tissues and male reproductive
      organs. In this study, pregnant rats were treated with 60 mg/kg ENU at day 13 of
      gestation, and their fetuses were examined from 1 to 48 hours after treatment
      (HAT) to find a clue for clarifying the mechanisms of the ENU fetotoxicity and
      teratogenicity. From 3 to 12 HAT, the moderate to marked increase in the number
      of pyknotic cells was detected in the fetal CNS, craniofacial mesenchymal
      tissues, gonads and so on. These pyknotic cells had nuclei positively stained by
      the TUNEL method, which is widely used for the detection of apoptotic nuclei, and
      they also showed electron microscopic characteristics identical to those of
      apoptotic cells. The present results strongly suggest that excess cell death by
      apoptosis in the fetal CNS, craniofacial tissues and gonads may have a close
      relation to the later occurrence of anomalies reported in these tissues following
      ENU-administration.

PMID- 10963115
TI  - Distribution of T-cell subsets and immunoglobulin-containing cells in nasal
      associated lymphoid tissue (NALT) of chickens.
AB  - The present study demonstrated the localization of the T-cell subsets (CD4+ and
      CD8+) and immunoglobulin (Ig)-containing cells (IgA, IgM, and IgG) in the nasal
      mucosa and its accessory structures. These lymphoid structures may be compared
      with nasal-associated lymphoid tissue (NALT) of rats and mice. In the chicken
      NALT, T-cell subsets were more widely distributed than Ig-containing cells,
      especially in large lymphoid accumulations restricted to the respiratory mucosa
      in the nasal cavity and the nasolacrimal duct. These lymphoid accumulations in
      the mucosa of the nasal cavity and nasolacrimal duct consisted of widely
      distributed CD8+ cells and deeply aggregated CD4+ cells adjacent to large
      germinal centers. In these lymphoid accumulations, IgG-containing cells were more
      frequently observed than IgM- and IgA-containing cells. T-cell subsets,
      predominantly CD8+ cells were more widely distributed in the duct epithelium of
      the lateral nasal glands than Ig-containing cells. Moreover, numerous CD8+ cells
      and a few Ig-containing cells were found in the chicken salivary glands,
      especially around the orifice of their ducts into the oral cavity. Therefore, it
      seems likely that the chicken NALT plays an important part in the upper
      respiratory tract, with a close relationship to the paraocular immune system.

PMID- 10963116
TI  - Immunohistochemical expression of retinoblastoma gene product (Rb), p53 protein,
      MDM2, c-erbB-2, HLA-DR and proliferation indices in human urinary bladder
      carcinoma.
AB  - Archival biopsy specimens from transitional cell bladder cancers (n=88) were
      analysed immunohistochemically for the expression of the retinoblastoma (Rb) gene
      protein, p53, mdm2, c-erbB-2, HLA-DR antigen and proliferation indices. An
      altered nuclear expression of Rb, p53 and mdm2 was observed in 55.2%, 33.3% and
      18.2% of tumors respectively. Cytoplasmic membrane immunoreactivity (>25% tumor
      cells) for c-erbB-2 was detected in 14.1% of tumors and aberrant HLA-DR antigen
      cytoplasmic staining (>5% of tumor cells) in 22.2% of the cases. P53
      overexpression was associated with higher tumor grade and stage. Aberrant HLA-DR
      antigen expression and PCNA were also correlated with the grade of
      differentiation and tumor stage. MIB1 was statistically correlated with stage.
      pRb scores and HLA-DR antigen expression were correlated with proliferation
      activity as determined by PCNA and MIB1 immunostaining. p53 protein was also
      strongly correlated with the proliferation index PCNA. A strong correlation
      between PCNA and MIB1 (p<0.0001) was also found. In addition a statistically
      positive correlation between p53 and HLA-DR antigen expression was observed. Our
      data show that, although pRb and p53 protein expressions are not associated
      between them, they may contribute to the growth fraction of the bladder cancer.
      In addition, p53 and HLA-DR antigen expression could be indicators of aggressive
      behavior of bladder cancer.

PMID- 10963117
TI  - Neuropeptides bombesin and calcitonin induce resistance to etoposide induced
      apoptosis in prostate cancer cell lines.
AB  - BACKGROUND: Neuroendocrine differentiation in prostatic carcinoma has been
      related to regulation of proliferation and metastatic potential and correlated
      with prognosis. More than 80% of prostate carcinomas initially respond to
      androgen ablation, but most relapse, due to the heterogeneous presence of
      androgen-dependent and independent clones. The pathways of cellular proliferation
      and apoptosis are inexorably linked to minimize the occurrence of neoplasia, and
      disfunction of apoptosis is proposed as a pathogenic process in malignant tumors.
      Androgen-dependent prostatic cancer cells undergo apoptosis after androgen
      deprivation, but not androgen-independent ones due to a defect in the initiation
      step. Anyway, they retain the basic cellular machinery to undergo apoptosis. We
      suggest a possible role of neuroendocrine differentiation in the onset and
      regulation of apoptosis in prostatic neoplasia. METHODS: LNCaP, PC-3 and DU 145
      prostatic cancer cell lines were induced to undergo apoptosis after treatment
      with etoposide alone or plus androgen ablation. We tested the role of
      neuropeptides bombesin and calcitonin at modulating etoposide induced apoptosis.
      RESULTS: Etoposide-induced apoptosis in all cancer cell lines was achieved. In
      LNCaP androgen ablation was also required. Apoptosis is prevented in all three
      lines when bombesin was added. Calcitonin addition prevents apoptosis in PC-3,
      LNCaP and in an etoposide dose-dependent way in DU 145. CONCLUSION: Neuropeptides
      bombesin and calcitonin can modulate the apoptotic response of prostate cancer
      cells by inducing resistance to etoposide-induced apoptosis, suggesting that
      neuropeptides can be used as a target of therapeutical approach in prostatic
      carcinoma.

PMID- 10963118
TI  - Diabetic state affects the innervation of gut in an animal model of human type 1
      diabetes.
AB  - Gastrointestinal symptoms in diabetic patients are commonplace, and are believed
      to be due, at least partly, to neuropathy of the gut. In the present study,
      therefore, some important neurotransmitters in the myenteric plexus were
      investigated in non-obese diabetic mice, an animal model of human type 1
      diabetes. For this purpose, immunocytochemistry was applied on sections from
      antrum, duodenum and colon, subsequently quantified by computerized image
      analysis. Whereas the number of vasoactive intestinal peptide (VIP)-positive
      neurons was increased in antral myenteric ganglia of diabetic mice, there was a
      decreased density of nerve fibres in muscularis propria. No difference was seen
      in the VIP of duodenum and colon. Acetylcholine-containing nerve fibres showed an
      increased volume density in muscularis propria of antrum and duodenum, but a
      decreased density in colon of diabetic mice, as compared with controls. There was
      a decreased number of neurons containing nitric oxide synthase (NOS) in myenteric
      ganglia of antrum and duodenum. No difference was seen in density of NOS
      containing nerve fibres in muscularis propria. There was no difference regarding
      neuropeptide Y (NPY) and galanin between diabetic and control mice; nor was there
      any difference between pre-diabetic NOD mice and controls regarding all bioactive
      substances investigated. It is concluded that the diabetic state affects the
      innervation of gut in this animal model. The present findings may be of some
      relevance to the gastrointestinal symptoms seen in patients with diabetes.

PMID- 10963119
TI  - Evaluation of the smooth muscle cell component and apoptosis in the varicose vein
      wall.
AB  - This study was designed to evaluate the role of the smooth muscle cell and the
      apoptosis in the pathogenesis of the varicose vein. Segments of saphenous vein
      were obtained from healthy subjects and from those with varicose veins. The vein
      specimens were subdivided according to subject age (younger or older than 50
      years) and according to the varicose vein source (distal or proximal).
      Morphological, ultrastructural, cell proliferation (anti-PCNA method) and cell
      death (TUNEL method) analysis were performed. The walls of healthy, control vein
      specimens acquired a more collagenous and papillomatous appearance with age. A
      slight increase in the number of TUNEL-positive cells was also observed in
      specimens from older subjects. The proportion of apoptotic cells was much greater
      in the varicose veins than in control specimens. Most cellular alterations were
      seen in proximal varicose segments obtained from young subjects. These specimens
      showed hypertrophic areas with a high degree of cellularity (both in the media
      and in the thickened intima). The highest proportion of apoptotic cells and
      collagenisation were also observed in these areas. The enhanced number of
      apoptotic cells in varicose veins observed mainly in proximal/young vein
      specimens could be responsible, at least in part, for the acceleration of the
      final fibrosclerotic process characteristic of the varicose vein wall.

PMID- 10963121
TI  - Microstructural analysis of bile: relevance to cholesterol gallstone
      pathogenesis.
AB  - The study of physical-chemical factors and pathways leading to cholesterol
      crystallization in bile has important clinical relevance. The major processes in
      cholesterol gallstone formation can be subdivided into nucleation, formation and
      precipitation of solid crystals (crystallization), crystal growth, crystal
      agglomeration and stone growth. A clear understanding of the microstructural
      events occurring during the earliest stages of these processes in bile is crucial
      for the identification of factors possibly delaying or preventing precipitation
      of cholesterol crystals and, therefore, gallstone formation in bile. Detection
      and characterization of microstructures in native and model biles can be achieved
      by both direct and indirect techniques. Direct imaging techniques provide more
      readily interpretable information, but sample preparation problems, particularly
      for electron microscopy, are a source of artifacts. Moreover, microscopic
      techniques provide only qualitative data without the possibility to quantitate or
      to analyse the composition of microstructures. Several indirect techniques have
      been used to obtain additional microstructural information about nucleating bile.
      These techniques have the disadvantage of often being model dependent in addition
      to constraints specific for each method. The systematic, judicious use of a
      combination of complementary direct and indirect techniques have led to a
      comprehensive understanding of the various microstructural processes and
      interactions occurring during bile secretion, flow in the biliary tract and
      storage in the gallbladder. This forms the basis for our current understanding of
      cholesterol nucleation, crystallization and gallstone formation.

PMID- 10963120
TI  - Current knowledge of dystrophin and dystrophin-associated proteins in the retina.
AB  - Dramatical development of molecular genetics has been disclosing the molecular
      mechanism of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy
      (BMD). DMD gene product, dystrophin, is a submembranous cytoskeletal protein and
      many dystrophin-associated proteins (DAPs) have been identified, such as
      utrophin, dystroglycans, sarcoglycans, syntrophins and dystrobrevins. Dystrophin
      and DAPs are very important proteins not only for skeletal, cardiac, or smooth
      muscles but also for peripheral and central nervous systems including the retina.
      The retina has been extensively examined to demonstrate that dystrophin and beta
      dystroglycan localize at the photoreceptor terminal, and their deficiency
      produces the abnormal neurotransmission between photoreceptor cells and ON
      bipolar cells. Dystrophin has seven isoforms in variable tissues, and the retina
      contains full-length dystrophin (Dp427), Dp260, and Dp71. Recent studies have
      demonstrated that Dp71 localizes in the inner limiting membrane (INL) and around
      the blood vessel, and Dp260 is expressed in the outer plexiform layer (OPL). beta
      dystroglycan is also expressed in the same regions as well as dystrophin, but it
      remains unclear whether other DAPs are expressed in the retina or not. It is
      generally assumed that dystrophin functions to stabilize muscle fibers with DAPs
      by linking the sarcolemma to the basement membrane, but its function in the
      retina is totally unknown so far.

PMID- 10963122
TI  - Transient structures of the human fetal brain: subplate, thalamic reticular
      complex, ganglionic eminence.
AB  - Morphological features of the subplate, the thalamic reticular complex and the
      ganglionic eminence, which represent three major transient structures of the
      human fetal forebrain, are summarized with special reference to their functional
      roles. The subplate harboring various neuronal types is an outstandingly wide
      zone subjacent to the cortical plate in the human fetal brain. Within the
      subplate various cortical afferents establish synaptic contacts for a prolonged
      period before entering the cortical plate. Therefore, the subplate is regarded as
      a "waiting compartment" which is required for the formation of mature cortical
      connections. Next to the thalamic reticular nucleus, within the fibers of
      internal capsule, the perireticular nucleus is located which has been established
      as a distinct entity during development. Its various neuronal types express a
      number of different neuroactive substances. Perinatally, the perireticular
      nucleus is drastically reduced in size. It is involved in the guidance of
      corticofugal and thalamocortical fibers. The ganglionic eminence is a conspicuous
      proliferative area that persists throughout nearly the entire fetal period. In
      the human fetal brain it extends medially upon the dorsal thalamic nuclei which
      receive precursor cells from the ganglionic eminence. Postmitotic cells in the
      marginal zone of the ganglionic eminence serve as an intermediate target for
      growing axons. On the whole, all three structures establish transient neural
      circuitries that may be essential for the formation of adult projections. The
      characteristics of the three transient structures are particularly relevant for
      developmental neuropathology as these structures may be damaged in disorders that
      preferentially occur in preterm infants.

PMID- 10963123
TI  - Histopathology and molecular pathology of synovial B-lymphocytes in rheumatoid
      arthritis.
AB  - B-cells of the rheumatoid synovial tissue are a constant part of and, in some
      histopathological subtypes, the dominant population of the inflammatory
      infiltrate, located in the region of tissue destruction. The pattern of B-cell
      distribution and the relationship to the corresponding antigen-presenting cells
      (follicular dendritic reticulum cells: FDCs) show a great variety. B-cells may
      exhibit (i) a follicular organization forming secondary follicles; (ii) follicle
      like patterns with irregularly formed FDC networks, and (iii) a diffuse pattern
      of isolated FDCs. Molecular analysis of immunoglobulin VH and VL genes from human
      synovial B-cell hybridomas and synovial tissue demonstrates somatic mutations due
      to antigen activation. The FDC formations in the synovial tissue may therefore
      serve as an environment for B-cell maturation, which is involved in the
      generation of autoantibodies. An autoantibody is defined as "pathogenic" if it
      fulfills the Witebsky-Rose-Koch criteria for classical autoimmune diseases:
      definition of the autoantibody; induction of the disease by transfer of the
      autoantibody; and isolation of the autoantibody from the disease-specific lesion.
      B-cells from rheumatoid synovial tissue show specificity for FcIgG, type II
      collagen, COMP, sDNA, tetanus toxoid, mitochondrial antigens (M2), filaggrin and
      bacterial HSPs. The contributions of these antigens to the pathogenesis of RA are
      still hypothetical. A possible contribution could derive from crossreactivity and
      epitope mimicry: due to crossreaction, an antibody directed originally against a
      foreign infectious agent could react with epitopes from articular tissues,
      perpetuating the local inflammatory process. The characteristic distribution
      pattern, the localisation within the area of tissue destruction, the hypermutated
      IgVH and IgVL genes, and their exclusive function to recognize conformation
      dependent antigens suggest a central role for B-cells in the inflammatory process
      of rheumatoid arthritis. Therefore, the analysis of synovial B-cell hybridomas
      and experimental expression of synovial IgVH and IgVL genes will help to
      characterise the antigens responsible for the pathogenesis of rheumatoid
      arthritis.

PMID- 10963124
TI  - Stretching molecular springs: elasticity of titin filaments in vertebrate
      striated muscle.
AB  - Titin, the giant protein of striated muscle, provides a continuous link between
      the Z-disk and the M-line of a sarcomere. The elastic I-band section of titin
      comprises two main structural elements, stretches of immunoglobulin-like domains
      and a unique sequence, the PEVK segment. Both elements contribute to the
      extensibility and passive force development of nonactivated muscle. Extensibility
      of the titin segments in skeletal muscle has been determined by
      immunofluorescence/immunoelectron microscopy of sarcomeres stained with sequence
      assigned titin antibodies. The force developed upon stretch of titin has been
      measured on isolated molecules or recombinant titin fragments with the help of
      optical tweezers and the atomic force microscope. Force has also been measured in
      single isolated myofibrils. The force-extension relation of titin could be
      readily fitted with models of biopolymer elasticity. For physiologically relevant
      extensions, the elasticity of the titin segments was largely explainable by an
      entropic-spring mechanism. The modelling explains why during stretch of titin,
      the Ig-domain regions (with folded modules) extend before the PEVK domain. In
      cardiac muscle, I-band titin is expressed in different isoforms, termed N2-A and
      N2-B. The N2-A isoform resembles that of skeletal muscle, whereas N2-B titin is
      shorter and is distinguished by cardiac-specific Ig-motifs and nonmodular
      sequences within the central I-band section. Examination of N2-B titin
      extensibility revealed that this isoform extends by recruiting three distinct
      elastic elements: poly-Ig regions and the PEVK domain at lower stretch and, in
      addition, a unique 572-residue sequence insertion at higher physiological
      stretch. Extension of all three elements allows cardiac titin to stretch fully
      reversibly at physiological sarcomere lengths, without the need to unfold
      individual Ig domains. However, unfolding of a very small number of Ig domains
      remains a possibility.

PMID- 10963125
TI  - Telomerase activity in cancer as a diagnostic and therapeutic target.
AB  - Major advances have been made in understanding the role of telomerase in cellular
      immortalization and carcinogenesis. Human telomeres undergo progressive
      shortening with cell division, and critical shortening of telomeres with cellular
      aging triggers a signal for cells to stop dividing and senesce. Telomerase is an
      enzyme that adds telomeric-repeated sequences to the ends of human chromosome
      DNA. Telomerase is active in the vast majority of tumors, but not in normal
      somatic tissues, and prevents progressive shortening of telomeres with cell
      division, probably giving tumor cells a growth advantage over normal cells.
      Highly-sensitive PCR-based TRAP (telomeric repeat amplification protocol) assay
      provided the means to analyze telomerase in a wide variety of tissues. Evidence
      has been accumulated that this assay may be useful as a potential diagnostic tool
      for cancer. The constituents of telomerase complex have recently been identified,
      and human telomerase reverse transcriptase (hTERT) has been found to be
      responsible for the enzymatic activity of telomerase. Detection of hTERT mRNA may
      therefore be useful for the screening and diagnosis of cancers. The mechanisms
      regulating hTERT expression have been extensively analyzed, and transcriptional
      regulation of hTERT has been found to be essential for hTERT expression, in which
      several nuclear factors including c-Myc play crucial roles. Understanding of such
      mechanisms might provide insight into molecular basis of human carcinogenesis and
      contributes to the development of novel cancer gene therapy targeting telomerase.

PMID- 10963126
TI  - The distribution of cholinergic neurons in the human central nervous system.
AB  - Choline acetyltransferase (ChAT), the enzyme responsible for the biosynthesis of
      acetylcholine, is presently the most specific marker for identifying cholinergic
      neurons in the central and peripheral nervous systems. The present article
      reviews immunohistochemical and in situ hybridization studies on the distribution
      of neurons expressing ChAT in the human central nervous system. Neurons with both
      immunoreactivity and in situ hybridization signals of ChAT are observed in the
      basal forebrain (diagonal band of Broca and nucleus basalis of Meynert), striatum
      (caudate nucleus, putamen and nucleus accumbens), cerebral cortex, mesopontine
      tegmental nuclei (pedunculopontine tegmental nucleus, laterodorsal tegmental
      nucleus and parabigeminal nucleus), cranial motor nuclei and spinal motor
      neurons. The cerebral cortex displays regional and laminal differences in the
      distribution of neurons with ChAT. The medial septal nucleus and medial habenular
      nucleus contain immunoreactive neurons for ChAT, which are devoid of ChAT mRNA
      signals. This is probably because there is a small number of cholinergic neurons
      with a low level of ChAT gene expression in these nuclei of human. Possible
      connections and speculated functions of these neurons are briefly summarized.

PMID- 10963127
TI  - Aging, methylation and cancer.
AB  - Alterations in methylation are widespread in cancers. DNA methylation of promoter
      associated CpG islands is an alternate mechanism to mutation in silencing gene
      function, and affects tumor-suppressor genes such as p16 and RBI, growth and
      differentiation controlling genes such as ER and many others. Evidence is now
      accumulating that some of these methylation changes may initiate in
      subpopulations of normal cells as a function of age and progressively increase
      during carcinogenesis. Age-related methylation appears to be widespread and is
      one of the earliest changes marking the risk for neoplasia. In colon cancer, we
      have shown a pattern of age-related methylation for several genes, including ER,
      IGF2, N33 and MyoD, which progresses to full methylation in adenomas and
      neoplasms. Hypermethylation of these genes is associated with gene silencing. Age
      related methylation involves at least 50% of the genes which are hypermethylated
      in colon cancer, and we propose that such age-related methylation may partly
      account for the fact that most cancers occur as a function of old age. Age
      related methylation, then, may be a fundamental mark of the field defect in
      patients with neoplasia. The causes of age-related methylation are still unknown
      at this point, but evidence points to an interplay between local predisposing
      factors in DNA (methylation centers), levels of gene expression and environmental
      exposure. The concept that age-related methylation is a predisposing factor for
      neoplasia implies that it may serve as a diagnostic risk marker in cancer, and as
      a novel target for chemoprevention. Studies in animal models support this
      hypothesis and should lead to novel approaches to risk-assessment and
      chemoprevention in humans.

PMID- 10963128
TI  - IL-8 expression in malignant melanoma: implications in growth and metastasis.
AB  - This review article has described briefly studies supporting the concept that IL
      8 expression and its regulation by inflammatory cytokines like IL-1 may play an
      important role in controlling the phenotypes associated with melanoma progression
      and metastasis. It is clear from the experiments presented here that IL-8 is an
      important autocrine multifunctional cytokine that modulates melanoma/cell
      proliferation, migration by induction of extracellular matrix degradation enzymes
      and induces neovascularization, all of which are critical for melanoma growth and
      metastasis. In addition, their expression in melanoma tumor specimens suggests an
      association between IL-8 expression and tumor aggressiveness. Further,
      inflammatory cytokines produced by either tumor cells or stromal cells may
      regulate IL-8 expression, which can control melanoma growth and enhance our
      current knowledge regarding melanoma progression and metastasis. Understanding
      these events and their significance will allow us to design novel therapeutic
      approaches for treatment of melanoma.

PMID- 10963129
TI  - Apoptosis regulating genes in neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms. They are
      relatively uncommon and characterised by a relatively indolent clinical course.
      The indolent nature of NETs has long been enigmatic and recent advances in
      apoptosis research have led to speculation regarding the role of programmed cell
      death in NET tumorigenesis. It is hoped that a fundamental molecular
      understanding will help explain these variant behaviors that are so evident to
      the clinician, and ultimately yield novel and more effective therapies. Recent
      studies have demonstrated that deregulation of programmed cell death may be a
      critical component in the multistep tumorigenesis of NETs and that the frequent
      expression of the BCL-2 oncoprotein in these tumors may contribute to their
      pathogenesis. The genetic complementation of simultaneously deregulated BCL-2 and
      c-MYC may be implicated in the multistep tumorigenesis of human NETs. It is also
      clear that numerous cellular gene products can and will be shown to impact upon
      apoptosis in NETs; some of these may even be molecules identified as oncoproteins
      or tumor suppressors. The major challenge will be to ascribe primary pathogenetic
      significance to tumor-associated derangements in expression of these molecules,
      and hopefully to then exploit our knowledge toward therapeutic benefit.

PMID- 10963130
TI  - Eosinophils and airway nerves in asthma.
AB  - In the lungs, neuronal M2 muscarinic receptors limit the release of acetylcholine
      from postganglionic cholinergic nerves. However, these receptors are not
      functional under certain circumstances in animal models of hyperreactivity such
      as occurs after exposure of sensitised animals to an allergen or during a
      respiratory tract virus infection. This loss of M2 receptor function leads to an
      increase in acetylcholine release from cholinergic nerves and thus is a mechanism
      for the vagally mediated hyperreactivity seen in these animals. Studies in animal
      models of hyperreactivity have shown that eosinophils localise to the airway
      nerves of sensitised animals after antigen challenge. Inhibiting this
      localisation of eosinophils either with an antibody to the eosinophil survival
      cytokine IL-5 or the eosinophil adhesion molecule VLA-4 prevents loss of M2
      muscarinic receptor function. It is likely that eosinophil MBP is responsible for
      the loss of M2 receptor function, since inhibiting eosinophil MBP with an
      antibody or neutralising MBP with heparin prevents this loss of function. These
      data are also supported by ligand binding studies where it has been shown that
      eosinophil MBP is an allosteric antagonist at neuronal M2 muscarinic receptors.
      Loss of function of lung neuronal M2 muscarinic receptors may also occur under
      certain circumstances in patients with asthma, although the mechanisms are not
      yet established.

PMID- 10963132
TI  - Tumor heterogeneity: morphological, molecular and clinical implications.
AB  - Malignant tumors are characterized by their great heterogeneity and variability.
      There are hundreds of different types of malignant tumors that harbour many
      oncogenic alterations. The tumor heterogeneity has important morphological,
      molecular and clinical implications. Except for some hematopoietic and
      lymphoproliferative processes and small cell infant tumors, there are not
      specific molecular alterations for most human tumors. In this review we summarize
      the most important aspects of carcinogenesis and chemoradiosensitivity of
      malignant cells. In this regard, some oncogenes such as neu, ras and bcl-2 have
      been associated with cellular resistance to treatment with anticancer agents. The
      knowledge of oncogenic alterations involved in each tumor can be important to
      correlate the morphological features, the genetic background, the prognosis and
      the clinical response to treatment with anticancer agents. Based on the molecular
      background of the tumor there are new cancer gene therapy protocols. For example
      using adenovirus Ela in tumors with overexpression of neu oncogene, inhibitors of
      tyrosine kinase specific for the PDGF receptor in glioma, inhibitors of farnesil
      transferase to prevent ras activity in tumors with mutations in the ras gene.

PMID- 10963131
TI  - Immunopathology of autoimmune gastritis: lessons from mouse models.
AB  - Autoimmune gastritis in humans is a chronic inflammatory disease of the stomach
      accompanied by specific destruction of gastric parietal and zymogenic cells
      resulting in pernicious anemia. Human gastritis can be accurately reproduced in
      mice and is characterised by autoantibodies to the alpha- and beta-subunits of
      the gastric H/K ATPase (the enzyme responsible for gastric acid secretion) and
      cellular destruction of parietal and zymogenic cells within the gastric gland.
      Studies with these mouse models have given us our current concepts of the
      immunopathogenesis of the gastritis. Mouse models have shown that a T cell
      response is generated to the alpha- and beta-subunits of the H/K ATPase and that
      an immune response to the beta-subunit seems to be required for disease
      initiation. Using these models, we have defined key events associated with a
      damaging autoimmune response to the gastric H/K ATPase. The mechanisms associated
      with the cellular destruction associated with autoimmune gastritis are not know,
      but may involve signaling through death inducing pathways such as the Fas/FasL
      and TNF/TNFR pathways. This knowledge should permit us to develop strategies to
      prevent and treat the gastritis.

PMID- 10963133
TI  - Mechanisms underlying eosinophil trafficking and their relevance in vivo.
AB  - After their formation in the bone marrow, eosinophils circulate with a short half
      life and are distributed throughout the body, especially in mucosal and sub
      mucosal regions. Although a small amount of these cells are normally seen in
      healthy tissue, blood and tissue eosinophilia is a hallmark of helminthic and
      allergic diseases. The role of eosinophils in the normal physiology of mucosal
      tissues is not understood, but there is good evidence to demonstrate that these
      cells protect the host at least against some intestinal helminths, specially
      those with a lung cycle. In addition, there are now many data that support a role
      for eosinophils in the pathophysiology of allergic diseases, such as asthma.
      Because helminthic diseases have been largely controlled in developed countries,
      there has been much interest in the development of drugs which affect eosinophil
      migration and/or activation in the tissue and which may, thus, be useful in the
      treatment of allergic conditions. The understanding of the mechanisms controlling
      eosinophil trafficking and/or activation are essential in the development of anti
      eosinophil-based therapeutic strategies. The present paper reviews aspects of
      eosinophil biology with emphasis on the role of eosinophils in parasitic
      infections and allergy, the basic mechanisms underlying the trafficking of
      eosinophils into tissue and how these can be modulated pharmacologically.

PMID- 10963134
TI  - Fos family members: regulation, structure and role in oncogenic transformation.
AB  - The members of the Fos protein family might be subdivided in two groups,
      according to their ability to transform rodent fibroblasts, transforming (c-Fos
      and FosB) and non-transforming (Fra-1 and Fra-2) proteins. Members of these
      groups are differently activated in response to external stimuli and possess
      different structural features. Importantly, whilst c-Fos and FosB contain
      multiple transactivation modules in their N- and C-terminal parts,
      transactivation domains are absent in the non-transforming Fos proteins. As a
      result, Fra-1 and Fra-2 though efficiently form dimers with the Jun proteins, are
      weak transcriptional activators and inhibit the c-Fos-dependent activation in
      transient transfection assay. The numerous experiments performed with the
      different Fos mutant proteins with impaired transforming ability, as well as with
      chimeric proteins revealed the importance of the transactivation function for
      transformation. Fra-1 and Fra-2 proteins albeit ineffectively triggering
      oncogenic transformation, are abundant in ras- and src-transformed murine and
      chicken fibroblasts, in neoplastic thyroid cells and in highly malignant mouse
      adenocarcinoma cells, which underwent mesenchymal transition. The abundance of
      the non-transforming Fos proteins in these systems might be mediated by a
      positive AP-l-dependent feedback mechanism, as well as by wnt signals.
      Furthermore, the manipulation of the Fra-1 expression level in thyroid and
      mammary tumor cells modulated the transcription of several tumor progression
      markers and affected cell morphology and invasiveness. These recent data
      demonstrate a novel function of non-transforming Fos proteins in the maintenance
      and progression of the transformed state. Interestingly, this function is
      independent of the documented invalidity of the Fra-1 and Fra-2 proteins as
      transcriptional activators in rodent fibroblasts.

PMID- 10963135
TI  - Modulation of EGFR gene transcription by secondary structures, a polymorphic
      repetitive sequence and mutations--a link between genetics and epigenetics.
AB  - The epidermal growth factor receptor (EGFR) plays a crucial role in growth,
      differentiation and motility of normal as well as tumor cells. The transduction
      of extracellular signals to the cytoplasm via the receptor not only depends on
      ligand binding, but is also determined by the receptor density on the cell
      surface. Therefore, in terms of cancer diagnosis and therapeutic approaches
      targeting EGFR it is decisive to know how the expression level of EGFR is
      controlled. We found that transcription activity declines with increasing numbers
      of CA dinucleotides of a highly polymorphic CA repeat in the first intron
      epidermal growth factor receptor gene. In vivo data from cultured cell lines
      support these findings, although other regulation mechanisms can compensate this
      effect. In addition, we showed that RNA elongation terminates at a site closely
      downstream of the simple sequence repeat (SSR) and that there are two separate
      major transcription start sites. Model calculations for the helical DNA
      conformation revealed a high bendability in the EGFR polymorphic region,
      especially if the CA stretch is extended. These data suggest that the CA-SSR can
      act like a joint bringing the promoter in proximity to a putative repressor
      protein bound downstream of the CA-SSR. The data suggest that this polymorphism
      is a marker for cancer linking genetic and epigenetic risk. Furthermore in breast
      cancer, heterozygous tumours with short CA-SSR showed an elevated EGFR-expression
      in contrast to tumours with longer CA-SSR. Tumours with loss of heterozygosity in
      intron 1 of egfr revealed an increased EGFR expression if the longer allele was
      lost. Moreover, deceased egfr gene dosages were significantly correlated to poor
      prognosis in breast cancer.

PMID- 10963136
TI  - Mast cell granule composition and tissue location--a close correlation.
AB  - This review provides a survey on mast cell heterogeneity, with aspects differing
      in humans and rodents or which are subject of conflicting evidence being
      discussed in greater detail. Mast cell subsets have been first defined in rats by
      their fixation and dye-binding properties, and detailed studies in humans and
      pigs reveal very similar observations. The dye-binding properties of rat mast
      cell subsets are causally related to the absence or presence of heparin in their
      granules. In humans, this relation has not been shown. Rodent mast cell subsets
      store different chymase-isoforms. In contrast, just a single chymase has been
      defined in humans, and mast cells are classified by the presence or relative
      absence of this chymase. Different investigators find quite different proportions
      of chymase-positive to chymase-negative mast cells. Tryptase(s) are found in most
      or every human mast cell, but in rodents, they have hitherto been essentially
      localised to mast cells in connective tissues. Human mast cell subsets may also
      be defined by their expression of receptors such as C5aR and possibly the beta
      chemokine receptor CCR3; the CCR3 expression seems to be related to the human
      mast cell chymase expression. Ultrastructural studies are helpful to distinguish
      human mast cell subsets, and allow to distinguish between chronic and acute
      activation. The phenotypical characteristics may change in association with
      inflammation or other disease processes. Studies in humans and pigs show changed
      dye-binding and fixation properties of the granules. Experimental rodent
      infection models reveal similar changes of chymase isoform expression. Human lung
      mast cells have been reported to strongly upregulate their chymase content in
      pulmonary vascular disease. This line of evidence can explain some inconsistent
      information on mast cell heterogeneity and may help to understand the
      physiological role of mast cells.

PMID- 10963137
TI  - The SH2 and SH3 adapter Nck: a two-gene family and a linker between tyrosine
      kinases and multiple signaling networks.
AB  - SH2 and SH3 adapter proteins connect cell surface tyrosine kinases to
      intracellular signaling networks. For instance, the SH3-SH2-SH3 adapter Grb2
      links receptor tyrosine kinases to the Ras pathway. Nck, composed of three SH3
      domains and one SH2 domain, represents a two-gene (alpha and beta) family in
      mammals. Nckalpha and Nckbeta are expressed in the same cells and appear to have
      distinct signaling specificity. Studies show that Nck plays a role in cell
      mitogenesis and morphogenesis. The former uses Ras-dependent and Ras-independent
      pathways. The latter appears to coordinate with the Cdc42/Rac>PAK1/WASp>actin
      cytoskeleton pathway. Understanding the specificity of Nckalpha and Nckbeta
      signal transduction will provide answers for the previously often conflicting
      observations.

PMID- 10963138
TI  - Recent studies on the biological action of parathyroid hormone (PTH)-related
      peptide (PTHrP) and PTH/PTHrP receptor in cartilage and bone.
AB  - Mice with a targeted deletion of parathyroid hormone (PTH)-related peptide
      (PTHrP) develop a form of dyschondroplasia resulting from diminished
      proliferation and premature maturation of chondrocytes. Abnormal, heterogeneous
      populations of chondrocytes at different stages of differentiation were seen in
      the hypertrophic zone of the mutant growth plate. Although the homozygous null
      animals die within several hours of birth, mice heterozygous for PTHrP gene
      deletion reach adulthood, at which time they show evidence of osteopenia.
      Therefore, PTHrP appears to modulate cell proliferation and differentiation in
      both the pre and post natal period. PTH/PTHrP receptor expression in the mouse is
      controlled by two promoters. We recently found that, while the downstream
      promoter controls PTH/PTHrP receptor gene expression in bone and cartilage, it is
      differentially regulated in the two tissues. 1alpha,25-dihydroxyvitamin D3
      downregulated the activity of the downstream promoter in osteoblasts, but not in
      chondrocytes, both in vivo and in vitro. Most of the biological activity of PTHrP
      is thought to be mediated by binding of its amino terminus to the PTH/PTHrP
      receptor. However, recent evidence suggests that amino acids 87-107, outside of
      the amino terminal binding domain, act as a nucleolar targeting signal.
      Chondrocytic cell line, CFK2, transfected with wild-type PTHrP cDNA showed PTHrP
      in the nucleoli as well as in the secretory pathway. Therefore, PTHrP appears to
      act as a bifunctional modulator of both chondrocyte proliferation and
      differentiation, through signal transduction linked to the PTH/PTHrP receptor and
      by its direct action in the nucleolus.

PMID- 10963139
TI  - Toward a molecular classification of the gliomas: histopathology, molecular
      genetics, and gene expression profiling.
AB  - As many as 100,000 new cases of brain tumor are diagnosed each year in the United
      States. About half of these are primary gliomas and the remaining half are
      metastatic tumors and non-glial primary tumors. Currently, gliomas are classified
      based on phenotypic characteristics. Recent progress in the elucidation of
      genetic alterations found in gliomas have raised the exciting possibility of
      using genetic and molecular analyses to resolve some of the problematic issues
      currently associated with the histological approach to glioma classification.
      Recently, immunohistochemical studies using novel proliferation markers have
      significantly advanced the assessment of tumor growth potential and the grading
      criteria of some tumor subtypes. Preliminary studies using cDNA array
      technologies suggest that the profiling of gene expression patterns may provide a
      novel and meaningful approach to glioma classification and subclassification.
      Furthermore, cDNA array technologies may also be used to identify candidate genes
      involved in glioma tumor development, invasion, and progression. This review
      summarizes current glioma classification schemes that are based on
      histopathological characteristics and discusses the potential for using cDNA
      array technology in the molecular classification of gliomas.

PMID- 10963140
TI  - Functional morphology of the equine pelvic flexure and its role in disease. A
      review.
AB  - The hindgut is the major site in the horse for nutrient digestion and absorption.
      Most of this activity occurs in the large intestinal compartments, i.e., cecum,
      right and left ventral colon and left and right dorsal colon. The colonic pelvic
      flexure is a short and narrow loop connecting the left ventral and left dorsal
      colon. It is not significant directly in digestive and absorptive processes but
      plays an important functional role in regulating colonic aboral and
      retropropulsive transit of digesta through its motility pacemaker activity. The
      pelvic flexure also contributes to the pathophysiology of colic, the leading
      cause of death in horses. Its narrow lumen may contribute to colonic impaction,
      and malfunctions of the pacemaker may contribute to volvuli and colonic
      displacements. Neuronal and ganglion density of the myenteric plexus is increased
      at the pelvic flexure and adjacent left dorsal colon pacemaker region.
      Contractile activity, vasoactive intestinal peptide (VIP) and neurokinins-1 and 
      3 are all enhanced in the pelvic flexure. The mucosa histologically resembles
      that of the ventral and dorsal colon, with apically-granulated principal cells
      and goblet cells lining the luminal surface. Clustered intranuclear inclusions
      resembling the cytoplasmic granules are also observed by electron microscopy in
      the principal cells as elsewhere in the horse colon. Further neuroendocrine and
      morphologic investigation of the pelvic flexure is warranted due to the great
      importance of this localized region for normal function and pathophysiology.

PMID- 10963141
TI  - Crescentic glomerulonephritis--a manifestation of a nephritogenic Th1 response?
AB  - Crescentic glomerulonephritis (GN) is the histopathological correlate of the
      clinical syndrome of rapidly progressive glomerulonephritis. Glomerular crescent
      formation complicates proliferative forms of GN and indicates severe disease with
      a poor renal prognosis. In the past 10 years evidence from experimental models of
      GN and from human disease has accumulated suggesting that crescentic
      glomerulonephritis is a manifestation of a delayed type hypersensitivity (DTH)
      like response to nephritogenic antigens. The elucidation of T helper 1 (Th1) and
      Th2 subsets in mice and in humans has led to the hypothesis that crescentic GN is
      a manifestation of a Th1 predominant DTH mediated immune response. Recent
      experiments performed mainly in a murine model of crescentic glomerulonephritis
      have tested this hypothesis. Crescent formation in this model is substantially
      interleukin (IL)-12 and interferon-gamma (IFN-gamma) dependent. Administration of
      IL-12, deletion of endogenous IL-4 or IL-10 results in enhanced disease, while
      administration of exogenous IL-4 and/or IL-10 reduces crescentic injury. These
      findings, together with the available evidence from human studies (examining the
      pattern of immune effectors in glomeruli, data on cytokine production by
      peripheral blood mononuclear cells and case reports of the induction of
      proliferative and/or crescentic GN by administration of IFN-gamma or IL-2)
      suggest that human crescentic GN is manifestation of a Th1 mediated DTH-like
      nephritogenic immune response.

PMID- 10963142
TI  - Current status of stentless aortic xenografts.
AB  - The introduction of the Toronto stentless porcine valve (SPV) (St. Jude,
      Minneapolis, MN), recently approved by the Food and Drug Administration following
      a 6-year multi-institutional clinical trial from 1991 to 1997, reflects an
      evolutionary pursuit of an ideal valve substitute, namely, low thrombogenicity,
      freedom from anticoagulation, durability, easy availability, resistance to
      infection, and easy implantability. Currently, four different types of valve
      replacement have been time tested: mechanical valves, cryopreserved aortic
      homograft, stented heterograft, and pulmonary autograft (Ross procedure), and
      none of the available valve substitutes meet all the criteria of an ideal valve.
      The mechanical valve's favorable properties of durability and easy implantability
      are susceptible to thrombus formation, which requires lifelong anticoagulation.
      Although the aortic homografts are durable, with low incidence of infection and
      thrombogenicity, their widespread application has been limited by the lack of
      availability. The pulmonary autograft, with its native aortic valve properties,
      has been shunned by some surgeons because it requires a demanding technical
      expertise in implantation and needs an allograft in the pulmonary position.
      Stented xenografts are characterized by "off-the-shelf" availability, freedom
      from anticoagulation, easy implantability, and low incidence of infection. Its
      major drawback has been its limited durability. Another limitation is its
      residual transvalvular gradient. A modified version, a stentless xenograft, has
      been introduced to improve hemodynamic profiles in the hope of subsequent
      superior structural durability and patient survival. Two valves have been
      approved by the Food and Drug Administration, the Toronto SPV and the Freestyle
      valve (Medtronic, Minneapolis, MN). At The Methodist Hospital and the Baylor
      College of Medicine, the Toronto SPV stentless valve has been our stentless
      xenograft valve of choice. We therefore review the historical evolution, design
      advantages, surgical techniques, and clinical outcomes of this valve.

PMID- 10963143
TI  - The surgical management of bacterial valvular endocarditis.
AB  - Bacterial endocarditis is an important cause of cardiac valvular problems. The
      diagnosis of bacterial endocarditis can be difficult, and, often, an aggressive
      clinical evaluation including serial blood cultures is necessary. The
      pathophysiology of endocarditis is changing with the rise of intravenous drug
      use; staphylococci are an increasingly common cause. Endocarditis often warrants
      surgical intervention. Operations for bacterial endocarditis range from valve
      repair to valve replacement to homograft replacement. The operations are
      technically challenging, but new methods of myocardial protection have markedly
      improved the surgical outcomes. Valve excision is an option for intravenous drug
      users with tricuspid valve endocarditis. Surgical management of endocarditis is a
      technically challenging but rewarding procedure that should be offered to
      appropriate patients.

PMID- 10963144
TI  - Pulmonary homografts: current status.
AB  - Pulmonary homografts are used more frequently in cardiac surgery. They are used
      primarily for reconstruction of the right ventricular outflow tract, both in
      children with complex congenital disease and in adults undergoing the Ross
      procedure for aortic valve replacement. They have been used for left ventricular
      outflow tract reconstruction, but they are less,durable in this high-pressure
      position. They have excellent hemodynamic characteristics, require no
      anticoagulation, and are free from problems of thromboembolism. However, there is
      concern that over time pulmonary homografts may develop stenosis secondary to low
      grade immune reactions. Even as they become more popular, a shortage of available
      grafts may limit their use.

PMID- 10963145
TI  - Current approaches to minimally invasive aortic valve surgery.
AB  - Minimally invasive as it applies to aortic valve surgery refers to the exposure
      required to perform the aortic procedure, because total cardiopulmonary bypass is
      still required. Initial experience used the anterior thoracotomy, but recent
      series report the ministernotomy or "J" incision as the preferred technique for
      exposure. Though pain, blood loss, and length of stay may not be significantly
      different when compared with the conventional technique, lower costs and earlier
      recovery may be achieved. Minimally invasive aortic valve surgery is a technique
      that is still evolving.

PMID- 10963146
TI  - How old is too old for heart transplantation?
AB  - Heart transplantation is considered the treatment of choice for patients with
      advanced heart failure. Given the excellent results with transplantation, there
      has been growing pressure to liberalize eligibility criteria, especially with
      regard to age. Registry data and early reports have indicated that there may be
      increased posttransplantation mortality in older patients. A number of single
      center reports have shown that survival of older patients may be similar to that
      of younger patients. The limited supply of donor hearts makes it imperative that
      careful consideration be given to transplantation results in older recipients and
      to the overall impact that expanding eligibility criteria for transplantation
      will have. The limited supply of donor hearts has also led to increased interest
      in the use of hearts from older donors. This review presents a current
      perspective on outcomes after heart transplantation in older recipients, use of
      older donor hearts, and the matching of donor and recipient risk.

PMID- 10963147
TI  - The use and misuse of immunologic monitoring after transplantation: approaches
      that have proved useful.
AB  - Current practice in the monitoring of cardiac transplants revolves around the use
      of the endomyocardial biopsy. While this is effective for the identification of
      an ongoing immune response in the graft, for years investigators have explored
      less invasive approaches in the hope of achieving the same goal by examining the
      patient's immune response. For a number of years, lymphocytes, their subsets, and
      their level of activation in the periphery were investigated. To a large degree,
      it was a lack of specificity in these approaches that led to their falling out of
      favor. Examination of donor-specific reactivity by means of lymphocyte
      proliferation assays has also been used; however, these approaches have been
      impeded by the time and effort required to accomplish them. During the last few
      years, flow cytometric cross-matching during the posttransplant period has been
      used at our institution. While this cross-matching focuses on the humoral immune
      responses, we have found it to be of value in identifying patients at risk of
      rejection and in allowing the assessment of treatment modalities used to treat
      ongoing rejection. While the perfect approach remains to be found, the potential
      advantages of immunologic monitoring would seem to justify continued study.

PMID- 10963148
TI  - Immunosuppressive therapies after heart transplantation: best, better, and
      beyond.
AB  - Despite the significant advances in transplantation immunology and
      immunosuppressive therapies over the past 30 years, current immunosuppressive
      regimens are still inadequate in the majority of cardiac transplant recipients.
      Although short- and long-term survival rates have improved significantly, only
      50% will survive 10 years and very few will survive 20 years. Complications of
      overimmunosuppression and underimmunosuppression account for the majority of
      these deaths. Only true "immunologic" tolerance can provide the outcome we
      pursue, namely, prolonged allograft function and otherwise normal immune function
      without chronic immunosuppressive therapy and its risks. Until a successful
      tolerance-inducing protocol is developed, we must use the current and upcoming
      immunosuppressive agents and techniques.

PMID- 10963149
TI  - Cardiac pacemakers in the transplanted heart: short term with the biatrial
      anastomosis and unnecessary with the bicaval anastomosis.
AB  - Sinus node dysfunction occurs commonly after orthotopic heart transplantation and
      may be caused by surgical trauma, ischemia to the sinus node, rejection, drug
      therapy and increasing donor age. In the past, using the standard biatrial
      technique described originally by Lower and Shumway, many series have reported
      permanent pacing in more than 10% of patients. Unlike sinus node dysfunction in
      nontransplanted patients, which typically worsens with time, sinus node
      dysfunction in the transplanted heart usually improves over a period of weeks to
      months. Delaying the implantation of a permanent pacemaker may render it
      unnecessary. The development of the bicaval technique for implantation of the
      donor heart appears to have decreased even further or even eliminated the need
      for early permanent pacing. Because sinus node dysfunction in the transplanted
      heart does not predict subsequent development of atrioventricular (AV) node
      dysfunction, rate-responsive atrial pacing should be used in the majority of
      cases. Even after appropriate pacing for sinus node dysfunction, the sinus node
      may recover and permanent pacing may be discontinued. AV conduction abnormalities
      are far less common and generally occur late after transplantation. Dual-chamber
      pacing is required and permanent pacing should be continued indefinitely.

PMID- 10963150
TI  - Therapy for primary cardiac tumors: is there a role for heart transplantation?
AB  - Primary cardiac tumors are rare clinical entities. Benign tumors are often
      amenable to surgical excision, whereas malignant tumors are seldom resectable.
      The literature has reported that 28 patients have undergone orthotopic heart
      transplantation for inoperable primary cardiac tumors. The results of these
      transplants are presented in this article. Of the 28 patients who underwent
      orthotopic heart transplantation for primary cardiac neoplasms, 7 patients had
      benign histology (fibroma-5, rhabdomyoma-1, and pheochromocytoma-1) and 21
      patients had malignant histology (sarcoma-15, malignant fibrohistiocytoma-3, and
      lymphoma-3). Mean survival in the patients with benign histology was 46 months,
      and the mean survival in the patients with malignant histology was 12 months.
      However, there were seven patients with malignant histology who had survived for
      a mean of 27 months without evidence of recurrent disease. An awareness by
      clinicians of the presenting clinical picture of these tumors is warranted in
      view of the potential for cure by resection or transplantation. Patients with
      benign primary cardiac tumors appear to benefit from the complete resection
      afforded by cardiectomy and transplantation. The role of transplantation for
      patients with malignant tumors remains unclear. Further experience and continued
      follow-up of these patients is necessary to ascertain the role of cardiac
      transplantation, radiation, and chemotherapy in the management of patients with
      primary tumors of the heart.

PMID- 10963151
TI  - Bibliography. Current world literature. Valvular heart disease.

PMID- 10963152
TI  - Bibliography. Current world literature. Heart transplantation.

PMID- 10963153
TI  - The classification of fractures.

PMID- 10963154
TI  - The teaching of trauma and orthopaedic surgery to the undergraduate in the United
      Kingdom.

PMID- 10963155
TI  - Does 'canal clearance' affect neurological outcome after thoracolumbar burst
      fractures?
AB  - Surgical decompression of the spinal canal is presently accepted worldwide as the
      method of treatment for thoracolumbar burst fractures with neurological deficit
      in the belief that neurological recovery may be produced or enhanced. Our
      clinical and laboratory experience, however, indicates that the paralysis occurs
      at the moment of injury and is not related to the position of the fragments of
      the fracture on subsequent imaging. Since the preoperative geometry of the
      fracture may be of no relevance, our hypothesis, backed by more than two decades
      of operative experience, is that alteration of the canal by 'surgical clearance'
      does not affect the neurological outcome. We have reviewed the existing world
      literature in an attempt to find evidence-based justification for the variety of
      surgical procedures used in the management of these fractures. We retrieved 275
      publications on the management of burst fractures of which 60 met minimal
      inclusion criteria and were analysed more closely. Only three papers were
      prospective studies; the remainder were retrospective descriptive analyses. None
      of the 60 articles included control groups. The design of nine studies was
      sufficiently similar to allow pooling of their results, which failed to establish
      a significant advantage of surgical over non-surgical treatment as regards
      neurological improvement. Significant complications were reported in 75% of
      papers, including neurological deterioration. Surgical treatment for burst
      fracture in the belief that neurological improvement can be achieved is not
      justified, although surgery may still occasionally be indicated for structural
      reasons. This information should not be withheld from the patients.

PMID- 10963156
TI  - Interobserver and intraobserver variation in classification systems for fractures
      of the distal humerus.
AB  - We assessed the inter- and intraobserver variation in classification systems for
      fractures of the distal humerus. Three orthopaedic trauma consultants, three
      trauma registrars and three consultant musculoskeletal radiologists independently
      classified 33 sets of radiographs of such fractures on two occasions, each using
      three separate systems. For interobserver variation, the Riseborough and Radin
      system produced 'moderate' agreement (kappa = 0.513), but half of the fractures
      were not classifiable by this system. For the complete AO system, agreement was
      'fair' (kappa = 0.343), but if only AO type and group or AO type alone was used,
      agreement improved to 'moderate' and 'substantial', respectively (kappa = 0.52
      and 0.66). Agreement for the system of Jupiter and Mehne was 'fair' (kappa =
      0.295). Similar levels of intraobserver variation were found. Systems of
      classification are useful in decision-making and evaluation of outcome only if
      there is agreement and consistency among observers. Our study casts doubt on
      these aspects of the systems currently available for fractures of the distal
      humerus.

PMID- 10963157
TI  - The posterolateral approach to the distal humerus for open reduction and internal
      fixation of fractures of the lateral condyle in children.
AB  - Our study describes a posterolateral approach to the distal humerus for open
      reduction and internal fixation of displaced fractures of the lateral condyle. A
      total of 20 patients had open reduction and internal fixation over a four-year
      period using this approach, and at a mean follow-up of 12 months had full union,
      range of movement and no complications, either clinical or radiological. This
      approach is well suited to the exact visualisation and accurate reduction of this
      difficult fracture with minimal dissection of tissues.

PMID- 10963158
TI  - Functional outcome after open supracondylar fractures of the humerus. The effect
      of the surgical approach.
AB  - We reviewed 26 patients who had had internal fixation of an open intra-articular
      supracondylar fracture of the humerus. All operations were performed using a
      posterior approach, 13 with a triceps split and 13 with an olecranon osteotomy.
      The outcome was assessed by means of the Mayo Elbow score, the Disability of the
      Arm, Shoulder and Hand (DASH) score and the SF-36 Physical Function score.
      Patients with an olecranon osteotomy had less good results.

PMID- 10963159
TI  - Antegrade or retrograde reamed femoral nailing. A prospective, randomised trial.
AB  - Retrograde femoral nailing is gaining in popularity. We report a prospective,
      randomised comparison of antegrade and retrograde procedures in 68 patients with
      69 fractures of the femoral shaft. All nails were inserted after appropriate
      reaming. There was no difference in operating time, blood loss, technical
      complications, size of nail or reamer, or transfusion requirements. There were
      more problems of length and rotation using a retrograde technique on a
      radiolucent table than with an antegrade approach on a fracture table. All
      fractures in both groups healed and there was no difference in the time taken to
      achieve union. Although retrograde nailing is a promising technique the skills
      required need practice. A longer period of follow-up is necessary to determine
      whether there are long-term problems in the knee after such surgery.

PMID- 10963161
TI  - Fracture after distraction osteogenesis.
AB  - We reviewed 173 patients undergoing distraction osteogenesis to determine the
      incidence, location and timing of fractures occurring as a complication of the
      procedure. There were 17 fractures in 180 lengthened segments giving an overall
      rate of fracture of 9.4%. Unexpectedly, the pattern and location of the fractures
      were very variable; six were within the regenerate itself, six at the junction
      between the regenerate and the original bone and five at distant sites in the
      limb. Of those occurring in the regenerate, five were noted to be associated with
      compression and partial collapse of the regenerate. In three patients collapse
      and deformity developed gradually in the distracted segment over the six months
      after removal of the frame. The method of treatment of these fractures should be
      chosen to take into account multiple factors, which are additional and often
      different from those to be considered during management of acute traumatic
      injuries. Internal fixation appears to be most appropriate for displaced
      fractures, although in small children, or in those in whom there has been, or is,
      infection of the screw tracks, a new period of treatment using external fixation
      may be needed. Fixation by intramedullary nailing was associated with a risk of
      infection, even if screw tracks were assessed as healthy at the time of insertion
      of the nail. Internal fixation with the use of plates is safe for displaced,
      unstable fractures in children.

PMID- 10963160
TI  - Nonunion of the femoral diaphysis. The influence of reaming and non-steroidal
      anti-inflammatory drugs.
AB  - We assessed factors which may affect union in 32 patients with nonunion of a
      fracture of the diaphysis of the femur and 67 comparable patients whose fracture
      had united. These included gender, age, smoking habit, the use of non-steroidal
      anti-inflammatory drugs (NSAIDs) the type of fracture (AO classification), soft
      tissue injury (open or closed), the type of nail, the mode of locking, reaming nu
      non-reaming, infection, failure of the implant, distraction at the fracture site,
      and the time to full weight-bearing. Patients with severe head injuries were
      excluded. Both groups were comparable with regard to gender, Injury Severity
      Score and soft-tissue injury. There was no relationship between the rate of union
      and the type of implant, mode of locking, reaming, distraction or smoking. There
      were fewer cases of nonunion in more comminuted fractures (type C) and in
      patients who were able to bear weight early. There was a marked association
      between nonunion and the use of NSAIDs after injury (p = 0.000001) and delayed
      healing was noted in patients who took NSAIDs and whose fractures had united.

PMID- 10963162
TI  - Gait characteristics of patients after proximal femoral replacement for malignant
      bone tumour.
AB  - We analysed the gait characteristics of 15 patients with prosthetic
      reconstruction of the proximal femur after resection of a malignant bone tumour
      using stride analysis and measurement of oxygen consumption. Compared with normal
      volunteers their gait was slower, with less cadence and reduced stride length.
      The mean net energy cost of free walking was 141% of normal. The degree of
      asymmetry of the single-limb support time correlated with the free-walking
      velocity and the net energy cost. If they used a single cane the subjects walked
      with less cadence, longer stride length, and prolonged single-limb support times.
      The net energy cost of walking and asymmetry of the single-limb support time had
      a negative correlation with the strength of the hip abductor muscles. Their
      walking performance was better than that of six subjects who had hip
      disarticulation.

PMID- 10963163
TI  - Bilateral avascular necrosis of the humeral trochleae after chemotherapy.
AB  - We describe a patient who developed avascular necrosis of both humeral trochleae
      after combination chemotherapy for acute lymphoblastic leukaemia. This presented
      as progressive stiffness of both elbows with little pain. Radiography and MRI
      confirmed the presence of avascular necrosis at both sites. This region
      corresponds to a watershed between the medial and lateral vascular arcades which
      supply the distal humerus and may explain the susceptibility of this bony region
      to avascular necrosis. Treatment involved capsulectomy of the elbow and removal
      of osteophytes giving a good functional outcome on both sides.

PMID- 10963164
TI  - Cytological diagnosis of skeletal lesions. Fine-needle aspiration biopsy in 110
      tumours.
AB  - We have previously shown that cytological diagnosis based on fine-needle
      aspiration biopsy (FNAB) is a safe and efficient method for the discrimination
      between benign, primary malignant and metastatic bony lesions. We have now
      studied metastatic lesions to assess the diagnostic accuracy and to ascertain
      whether FNAB allows identification of the primary lesion. Between 1990 and 1997,
      447 patients were referred for diagnosis of skeletal lesions of unknown type. Of
      these 119 proved to have metastatic disease, either myeloma or lymphoma. Nine
      were excluded leaving 110 consecutive patients with metastatic carcinoma (80),
      myeloma (16) or lymphoma (14). FNAB gave a correct diagnosis in 102 of the 110
      patients (93%). In eight it was inconclusive. It correctly diagnosed 15 of 16
      patients with myeloma, 12 of 14 with lymphoma, and 75 of 80 with metastatic
      carcinoma. Furthermore, the site and type of malignancy were correctly suggested
      in two-thirds of patients with metastatic carcinoma. Overall, only seven open
      biopsies were carried out. We conclude that time-consuming and costly
      investigations can be reduced by choosing FNAB as the initial diagnostic method
      for skeletal lesions of unknown origin. The choice of radiological examinations,
      laboratory tests and surgical biopsies can be determined by using FNAB.

PMID- 10963165
TI  - Anatomy of the medial femoral circumflex artery and its surgical implications.
AB  - The primary source for the blood supply of the head of the femur is the deep
      branch of the medial femoral circumflex artery (MFCA). In posterior approaches to
      the hip and pelvis the short external rotators are often divided. This can damage
      the deep branch and interfere with perfusion of the head. We describe the anatomy
      of the MFCA and its branches based on dissections of 24 cadaver hips after
      injection of neoprene-latex into the femoral or internal iliac arteries. The
      course of the deep branch of the MFCA was constant in its extracapsular segment.
      In all cases there was a trochanteric branch at the proximal border of quadratus
      femoris spreading on to the lateral aspect of the greater trochanter. This branch
      marks the level of the tendon of obturator externus, which is crossed posteriorly
      by the deep branch of the MFCA. As the deep branch travels superiorly, it crosses
      anterior to the conjoint tendon of gemellus inferior, obturator internus and
      gemellus superior. It then perforates the joint capsule at the level of gemellus
      superior. In its intracapsular segment it runs along the posterosuperior aspect
      of the neck of the femur dividing into two to four subsynovial retinacular
      vessels. We demonstrated that obturator externus protected the deep branch of the
      MFCA from being disrupted or stretched during dislocation of the hip in any
      direction after serial release of all other soft-tissue attachments of the
      proximal femur, including a complete circumferential capsulotomy. Precise
      knowledge of the extracapsular anatomy of the MFCA and its surrounding structures
      will help to avoid iatrogenic avascular necrosis of the head of the femur in
      reconstructive surgery of the hip and fixation of acetabular fractures through
      the posterior approach.

PMID- 10963166
TI  - Revision of failed total hip arthroplasty with a proximal femoral modular
      cemented stem.
AB  - We have designed a modular cemented femoral component for revision of failed
      total hip arthroplasty in which deficiency of the proximal femur is such as to
      require a variable extrafemoral portion of the stem. We present the results of
      the first 74 operations in 72 patients; 56 of the patients had grade-3 or grade-4
      femoral deficiency as defined by Gustilo and Pasternak and 24 had fractures of
      the proximal femur, of which 22 were periprosthetic. There was or had been
      infection in 19 hips. At a mean follow-up of 5 years 9 months (1 to 12 years)
      nine stems were radiologically loose of which three had been revised. There were
      no failures in 45 cases in which there was fixation of the distal stem of 10 cm
      or more. Dislocation occurred in nine patients and there were four cases of
      infection in the 19 which were, or had been, infected previously. There were no
      neurovascular complications and no intraoperative femoral fractures. The femoral
      bone stock improved radiologically in 45 hips of which 29 showed considerable
      reformation of the proximal femur; 27 remained unchanged and two showed
      increasing osteoporosis.

PMID- 10963167
TI  - Two-stage uncemented revision hip arthroplasty for infection.
AB  - We treated 50 consecutive patients with infected total hip arthroplasties
      according to a standard protocol. Previous surgery to eradicate the infection had
      been attempted in 13 patients and discharging sinuses were present in 20.
      Aspiration arthrography was routinely carried out before our interventions. The
      first stage was a meticulous removal of all foreign and potentially infected
      material. Samples were taken for culture and a thorough lavage carried out.
      Antibiotic-loaded beads were placed in the femoral shaft and an antibiotic-loaded
      cement ball in the acetabulum. At the second stage an uncemented arthroplasty was
      introduced. Bone allograft was used in 18 patients. The interval between
      procedures was usually three weeks, but this was extended if the wound was slow
      to heal or there was extensive bony destruction. Appropriate antibiotics were
      given for three months. At a mean follow-up of 5.8 years the rate of reinfection
      was 8% (4 patients). Two of these patients have had another, successful, two
      stage revision. At this medium-term review, a satisfactory clinical and
      radiological outcome was obtained in all except two patients.

PMID- 10963168
TI  - Neurophysiological tests of respiratory function by compound muscle action
      potentials from the diaphragm. Detection of lesions in the higher cervical cord.
AB  - We recorded compound muscle action potentials (CMAPs) from the diaphragm in 15
      normal volunteers, nine patients with lesions of the lower cervical cord (C5 to
      C8), one completely quadriplegic patient (C6) and seven patients with lesions at
      a higher cervical level (C1 to C4). Transcranial magnetic stimulation and
      electrical stimulation of the phrenic nerve were carried out. When the centre of
      the coil was placed on the interauricular line at a point 3 cm lateral to the
      vertex on the scalp, the CMAPs from the diaphragm had the largest amplitude and
      the shortest latency. There was no difference in the mean latency of the CMAPs
      recorded by transcranial magnetic stimulation in the normal volunteers and in the
      patients with lesions of the lower cervical cord. In the quadriplegic patient,
      the latency of the CMAPs was not delayed, but was prolonged in the patients with
      lesions at a higher level. Those evoked by electrical stimulation of the phrenic
      nerve were not prolonged in the patients with higher lesions. Our findings
      suggest that the prolongation of the latency by transcranial magnetic stimulation
      reflects dysfunction of the higher cervical cord. The combination of transcranial
      magnetic stimulation and electrical stimulation of the phrenic nerve can detect
      the precise level of the lesion in the motor tract to the diaphragm.

PMID- 10963169
TI  - Recurrent instability of the elbow in the Ehlers-Danlos syndrome. A report of
      three cases and a new technique of surgical stabilisation.
AB  - We present three cases of recurrent instability of the elbow in association with
      the Ehlers-Danlos syndrome. The pattern of instability has not previously been
      reported. We describe our procedure for achieving stability using a bone graft to
      the olecranon fossa which gave a functional range of movement.

PMID- 10963170
TI  - The Roper-Tuke total elbow arthroplasty. 4- to 10-year results of an
      unconstrained prosthesis.
AB  - We report the results of a series of 59 unconstrained total arthroplasties of the
      elbow after a mean follow-up of 6.5 years (4 to 10). All the patients had
      rheumatoid arthritis. The indication for surgery was pain in all but one. Outcome
      was assessed by the Mayo Elbow Performance Index (MEPI). Of the 59
      arthroplasties, two were lost to follow-up. Ten patients died, but as two of
      their arthroplasties were failures we included them in the results. The outcome
      in the remaining 49 was excellent in 26 (53%), good in 15 (31%), fair in one (2%)
      and poor or a failure in seven (14%). There was an improvement in the pain score
      (p < 0.001), movement (p < 0.001) and function (p < 0.001). Two patients
      developed instability, but neither required further surgery. There was a mean
      increase of 21 degrees in flexion and of 7 degrees in extension. The overall rate
      of complications was 33.9%. Lesions of the ulnar nerve, one of which did not
      recover, occurred in four patients, deep infection in two and stiffness in five.
      The rates of complications were similar to those in recent reports of other elbow
      arthroplasties. We carried out a radiological analysis of 39 arthroplasties which
      showed radiolucent lines around the humeral component in 22 and the ulnar
      component in 15. There were lower scores on the MEPI for those with radiolucent
      lines around the humeral component.

PMID- 10963171
TI  - The Sprengel deformity. Morphometric analysis using 3D-CT and its clinical
      relevance.
AB  - We evaluated scapular dysplasia and malposition in 15 patients with the Sprengel
      deformity using three-dimensional CT (3D-CT). The shape, height-to-width ratio,
      the areas of both scapulae, the anterior curvature of the supraspinous portion
      and glenoid version were assessed on scapular posterior, medial and inferior
      views. The degree of rotation and superior displacement were measured on the
      trunk posterior view. The omovertebral connection was also assessed and
      correlated with the operative findings. Most of the affected scapulae had a
      characteristic shape with a decrease in the height-to-width ratio and were larger
      than the contralateral scapulae. There was an inverse relationship between
      scapular rotation and superior displacement. The typical curve of the
      supraspinous portion of the scapula was seen in only three cases. There was no
      significant difference in glenoid version. The point of tethering of the
      omovertebral connection may determine the shape, rotation and superior
      displacement of the scapula. 3D-CT was helpful in delineating the deformity in
      detail, and in planning scapuloplasty.

PMID- 10963172
TI  - Involuntary positional instability of the shoulder in adolescents and young
      adults. Is there any benefit from treatment?
AB  - We diagnosed 50 patients (58 shoulders) with a mean age at presentation of 17.3
      years, as having involuntary positional instability of the shoulder. They were
      managed by a programme consisting of a careful explanation, analysis of abnormal
      muscle couples and then muscle retraining carried out by a specialist
      physiotherapist. The mean follow-up was two years. Six shoulders had a poor
      result, but 52 were graded as good to excellent. Nine patients (12 shoulders)
      relapsed and required further episodes of retraining. In our experience,
      involuntary positional instability of the shoulder causes symptoms which
      interfere with normal activities; these can be controlled by a treatment plan of
      retraining of the muscle pattern with functional benefit. Only 19 of the patients
      were referred with a diagnosis of positional instability. There should be more
      awareness of this rather uncommon condition. Surgery is not indicated in these
      patients.

PMID- 10963173
TI  - Effectiveness of an insole with a lateral wedge for idiopathic osteonecrosis of
      the knee.
AB  - For the purpose of investigating the effect of an insole with a lateral wedge, we
      studied 30 patients (31 knees) aged from 46 to 78 years with idiopathic
      osteonecrosis of the knee for at least three years. The 18 knees treated with an
      insole (group I) were matched by age, gender, obesity index, area of lesion,
      femorotibial angle, stage, and clinical evaluation with 13 treated conservatively
      without an insole (group II). The clinical results, as rated by a knee score,
      improved significantly more in group I than in group II. Radiologically, the
      necrotic area and ratio decreased in group I, whereas in group II they increased.
      In advanced cases, with stage 4 or a femorotibial angle of more than 180 degrees,
      the use of an insole did not improve the clinical or radiological findings. The
      insole is a valuable method of conservative treatment for the early stages of
      osteonecrosis of the medial femoral condyle.

PMID- 10963174
TI  - Preoperative haemoglobin and warfarin response.
AB  - There is a narrow line between the benefits and risks of anticoagulant therapy.
      Many factors influence a patient's response to warfarin, and careful monitoring
      is required to ensure that the therapeutic level of anticoagulation is achieved.
      The purpose of this retrospective review was to examine the relationship between
      the postoperative response to warfarin and the preoperative level of haemoglobin.
      The results showed that lower preoperative levels of haemoglobin are associated
      with an increased response to warfarin (p = 0.01).

PMID- 10963175
TI  - Evaluation of the deformity in club foot by somatosensory evoked potentials.
AB  - Somatosensory evoked potentials (SSEPs) measure the conduction pathways from the
      periphery to the brain and can demonstrate the site of neurological impairment in
      a variety of locomotor conditions. SSEPs were studied in 44 children (64 feet)
      with surgically corrected club feet. Four children had unreproducible responses,
      18 showed abnormal recordings and 22 showed normal responses. In a further 31
      feet (21 children) subjected to motor electrophysiological tests, 16 (52%) were
      abnormal. Overall, 44 of 95 feet (46%) showed abnormal SSEPs or motor
      electrophysiological tests. Neurological abnormality was related both to the
      severity of the deformity and the surgical outcome. It was seen in 38% of feet
      with grade-2 and in 53% of feet with grade-3 deformity. A fair surgical result
      was obtained in 36% of feet with a conduction deficit and in only 6% with no
      abnormality. These results suggest an association between neurological
      abnormality as demonstrated by SSEPs or motor electrophysiological studies and
      the severity of deformity in club foot and its response to surgical treatment.

PMID- 10963176
TI  - The outcome of treatment of trigger thumb in children.
AB  - Our aim was to determine the outcome of the treatment of trigger thumb in
      children. There was a rate of spontaneous recovery of 49% in those children whose
      thumbs were observed before a final decision to operate was made. Spontaneous
      recovery occurred more commonly in children over 12 months old. All patients
      treated by operation had a satisfactory outcome with few complications. The
      overall rate of recurrence was 4.0% and it was more common in younger children.
      Our results suggest that a conservative approach to surgery for this condition
      could be adopted.

PMID- 10963177
TI  - Relapse in staged surgery for congenital talipes equinovarus.
AB  - Between 1988 and 1995, we studied 91 club feet from a series of 120 recalcitrant
      feet in 86 patients requiring surgical treatment. There were 48 boys and 20
      girls. The mean age at operation was 8.9 months. Surgery consisted of an initial
      plantar medial release followed two weeks later by a posterolateral release. This
      strategy was adopted specifically to address the problems of wound healing
      associated with single-stage surgery and to ascertain the rate of relapse after a
      two-stage procedure. Immobilisation in plaster was used for three months followed
      by night splintage. The feet were classified preoperatively and prospectively
      into four grades according to the system suggested by Dimeglio et al. Grade-1
      feet were postural and did not require surgery. All wounds were closed primarily.
      One superficial wound infection occurred in a grade-4 foot and there were no
      cases of wound breakdown. The rate of relapse was 20.4% in grade-3 and 65.4% in
      grade-4 feet. Two-stage surgery for the treatment of club foot seems to be
      effective in the reduction of wound problems but does not appear to give
      significantly better results in terms of relapse when performed for more severe
      deformities.

PMID- 10963178
TI  - The role of coagulation abnormalities in the development of Perthes' disease.
AB  - Recent reports have suggested an association between Perthes' disease and an
      underlying thrombophilic or hypofibrinolytic tendency. In Northern Ireland there
      is a high incidence of Perthes' disease (11.7 per 100,000 or 1 in 607 children)
      in a stable paediatric population. We reviewed 139 children with Perthes' disease
      and compared them with a control group of 220 aged- and gender-matched healthy
      primary schoolchildren with similar racial and ethnic backgrounds. There were no
      significant deficiencies of antithrombotic factors protein C, protein S,
      antithrombin III or resistance to activated protein C. A total of 53 (38.1%) of
      the children with Perthes' disease had a prolonged activated partial
      thromboplastin time (>38) compared with 13 (5.9%) of the control group (p <
      0.001). Our findings have shown that using standard assays, thrombophilia
      secondary to antithrombotic factor deficiency or resistance to activated protein
      does not appear to be an aetiological factor for Perthes' disease. The cause of
      the prolonged activated partial thromboplastin time, usually associated with a
      clotting factor deficiency, is under further investigation.

PMID- 10963179
TI  - Changes in the proportions of peripheral blood lymphocytes in patients with worn
      implants.
AB  - We compared the peripheral blood and periprosthetic tissues of 53 patients at
      revision arthroplasty with those of 30 patients at primary arthroplasty to
      determine whether there is a systemic difference in lymphocytes in patients with
      worn hip implants. The absolute number and relative proportion of lymphocytes
      bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were
      compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial
      membrane as well as with a semiquantitative estimate of metal and polyethylene
      particles, necrosis and chronic inflammation and the total concentration of
      metals within the periprosthetic tissues. There was a significant increase in the
      relative proportion of CD2-positive T-cells and CD16-positive natural killer
      cells in the peripheral blood at revision arthroplasty compared with primary
      arthroplasty and an increased proportion of CD8-positive T-cells and a decreased
      ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control
      patients, who went on to have revision surgery, had values at primary
      arthroplasty which were similar to those of patients at the time of revision
      surgery. These differences did not correlate with the local concentration of
      metal, plastic or cement or inflammatory response or the type of prosthesis. An
      inverse correlation was noted between the necrosis in the periprosthetic tissue
      and both the local production of IL-6 and the absolute numbers of T-cells in
      peripheral blood. We conclude that there may be several cell-mediated systemic
      immune responses to aseptic loosening, at least one of which may be directly
      related to events in the periprosthetic tissues. We cannot exclude the
      possibility that the changes in the proportion of CD8-positive cells reflected a
      predisposition, rather than a reaction, to loosening of the implant.

PMID- 10963180
TI  - The effect of cyclic pressure on human monocyte-derived macrophages in vitro.
AB  - Aseptic loosening and osteolysis around prosthetic joints are the principal
      causes of failure and consequent revision. During this process activated
      macrophages produce cytokines which are thought to promote osteolysis by
      osteoclasts. Changes in pressure within the space around implants have been
      proposed as a cause of loosening and osteolysis. We therefore studied the effect
      of two different regimes of cyclic pressure on the production of interleukin
      1beta (IL-1beta), IL-6 and tumour necrosis factor-alpha (TNF-alpha) by cultured
      human monocyte-derived (M-D) macrophages. There was a wide variation in the
      expression of cytokines in non-stimulated M-D macrophages from different donors
      and therefore cells from the same donor were compared under control and
      pressurised conditions. Both regimes of cyclic pressure were found to increase
      expression of IL-6 and TNF-alpha. Expression of IL-1beta was increased by a
      higher-frequency regime only. Our findings suggest that M-D macrophages are
      activated by cyclic pressure. Further work will be required to understand the
      relative roles of frequency, amplitude and duration of applied pressure in the
      cellular effects of cyclic pressure in this system.

PMID- 10963181
TI  - Glucose metabolic analysis of musculoskeletal tumours using 18fluorine-FDG PET as
      an aid to preoperative planning.
AB  - We performed positron emission tomography (PET) with 18 fluorine-fluoro-2-deoxy-D
      glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in
      order to evaluate its role in operative planning. The standardised uptake value
      (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions,
      the cases were divided into high (> or =1.9) and low (< 1.9) SUV groups. The
      sensitivity of PET for correctly diagnosing malignancy was 100% with a
      specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for
      metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results
      suggest that the SUV may be useful in differentiating malignant tumours from
      benign lesions. However, some of the latter, such as schwannomas, had high SUVs
      so that biopsy or wide resection was selected as the first operation. Thus, some
      other quantitative analysis may be required for preoperative planning in cases of
      high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain
      reaction revealed that the RNA message of a key enzyme in glucose metabolism,
      phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only
      high FDG-uptake lesions, suggesting that a high expression of the PHI message may
      be associated with accumulation of FDG in musculoskeletal tumours.

PMID- 10963182
TI  - Expression of growth factors, cytokines and matrix metalloproteinases in frozen
      shoulder.
AB  - Frozen shoulder is a chronic fibrosing condition of the capsule of the joint. The
      predominant cells involved are fibroblasts and myofibroblasts which lay down a
      dense matrix of type-I and type-III collagen within the capsule. This
      subsequently contracts leading to the typical features of pain and stiffness.
      Cytokines and growth factors regulate the growth and function of the fibroblasts
      of connective tissue and remodelling of the matrix is controlled by the matrix
      metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether
      there was an abnormal expression or secretion of cytokines, growth factors and
      MMPs in tissue samples from 14 patients with frozen shoulder using the reverse
      transcription/polymerase chain reaction (RT/PCR) technique and to compare the
      findings with those in tissue from four normal control shoulders and from five
      patients with Dupuytren's contracture. Tissue from frozen shoulders demonstrated
      the presence of mRNA for a large number of cytokines and growth factors although
      the frequency was only slightly higher than in the control tissue. The frequency
      for a positive signal for the proinflammatory cytokines Il-beta and TNF-alpha and
      TNF-beta, was not as great as in the Dupuytren's tissue. The presence of mRNA for
      fibrogenic growth factors was, however, more similar to that obtained in the
      control and Dupuytren's tissue. This correlated with the histological findings
      which in most specimens showed a dense fibrous tissue response with few cells
      other than mature fibroblasts and with very little evidence of any active
      inflammatory cell process. Positive expressions of the mRNA for the MMPs were
      also increased, together with their natural inhibitor TIMP. The notable exception
      compared with control and Dupuytren's tissue was the absence of MMP-14, which is
      known to be a membrane-type MMP required for the activation of MMP-2 (gelatinase
      A). Understanding the control mechanisms which play a part in the pathogenesis of
      frozen shoulder may lead to the development of new regimes of treatment for this
      common, protracted and painful chronic fibrosing condition.

PMID- 10963183
TI  - The image intensifier as an operating table: a dangerous practice.

PMID- 10963184
TI  - The image intensifier as an operating table: a dangerous practice.

PMID- 10963185
TI  - The image intensifier as an operating table: a dangerous practice.

PMID- 10963186
TI  - Intra-articular steroids after arthroscopy for osteoarthritis of the knee.

PMID- 10963187
TI  - Intraoperative bacterial contamination in operations for joint replacement.

PMID- 10963188
TI  - Medical migration and inequity of health care.

PMID- 10963189
TI  - Relation between cryptic intestinal lymphoma and refractory sprue.

PMID- 10963190
TI  - Sirolimus and cyclosporin for renal transplantation.

PMID- 10963191
TI  - Radioimaging to identify myocardial cell death and probably injury.

PMID- 10963192
TI  - Relevance of mitochondrial DNA in cancer.

PMID- 10963193
TI  - Factor V Leiden paradox: risk of deep-vein thrombosis but not of pulmonary
      embolism.

PMID- 10963194
TI  - Aggressive strategies for treating aggressive rheumatoid arthritis: has the case
      been proven?

PMID- 10963195
TI  - Hospital mortality in relation to staff workload: a 4-year study in an adult
      intensive-care unit.
AB  - BACKGROUND: Few studies have examined mortality rates in relation to the workload
      of hospital staff. We investigated this issue in one adult intensive-care unit
      (ICU) in the UK. METHODS: We measured ICU workload per shift during each
      patient's stay for all admissions between 1992 and 1995 that met criteria for
      adjustment of mortality risk by the APACHE II equation (n=1050). APACHE II data
      were validated by one observer. Measures of workload in each patient's stay
      included occupancy, total ICU nursing requirement as defined by the UK Intensive
      Care Society, and the ratio of occupied to appropriately staffed beds. Over the
      period, staffing was appropriate for between 4.1 and 5.3 occupied beds (1.3
      nurses per patient). FINDINGS: There were 337 deaths, 49 more (95% CI 34-65) than
      predicted by the APACHE II equation. Median occupancy was 5.8 beds, and median
      nursing requirement was 1.6 per patient. On multiple logistic regression
      analysis, adjusted mortality was more than two times higher (odds ratio 3.1 [1.9
      5.0]) in patients exposed to high than in those exposed to low ICU workload,
      defined by average nursing requirement per occupied bed and peak occupancy; the
      unadjusted odds ratio for this comparison was 4.0 (2.6-6.2). After exclusion of
      measures of nursing requirement, adjusted mortality increased with the ratio of
      occupied to appropriately staffed beds during each patient's stay. All logistic
      regression models fitted the data satisfactorily. INTERPRETATION: Variations in
      mortality may be partly explained by excess ICU workload. This methodology may
      have implications for planning and clinical governance.

PMID- 10963196
TI  - Pancreatic cancer detection with magnetic resonance cholangiopancreatography and
      endoscopic retrograde cholangiopancreatography: a prospective controlled study.
AB  - BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive
      and increasingly used procedure in cases involving biliary and pancreatic
      diseases. However, the accuracy of MRCP in differential diagnosis between
      pancreatic cancer and chronic pancreatitis has never been documented in a large
      prospective controlled study. METHODS: 124 patients were recruited for the study,
      selected from 141 consecutive patients with an average age of 55 years (range 19
      80) who presented to our department between February, 1996, and January, 1998,
      with a strong clinical suspicion of pancreatic cancer. MRCP images were
      interpreted by a radiologist and a gastroenterologist who were unaware of the
      clinical diagnosis of patients. The exact diagnosis was based upon histological
      evidence from biopsy examination (surgical and fine needle biopsy) or a follow-up
      of at least 12 months. FINDINGS: Of the 124 patients, 37 (30%) had pancreatic
      carcinoma; 17 (14%) had other neoplastic pancreatic diseases; 57 (46%) had
      chronic pancreatitis; 13 (10%) pancreatic ducts were clear. The sensitivity of
      MRCP with respect to diagnosing pancreatic cancer was 84% and its specificity
      97%. The corresponding values for endoscopic retrograde cholangiopancreatography
      (ERCP) were 70% and 94%, respectively. INTERPRETATION: MRCP is as sensitive as
      ERCP when detecting pancreatic carcinomas. Furthermore, it is feasible to presume
      that the use of MRCP may prevent inappropriate explorations of the pancreatic and
      common bileducts in cases of suspected pancreatic carcinomas, where
      interventional endoscopic therapy (ie, palliative common-bileduct drainage) is
      unlikely.

PMID- 10963197
TI  - Efficacy of sirolimus compared with azathioprine for reduction of acute renal
      allograft rejection: a randomised multicentre study. The Rapamune US Study Group.
AB  - BACKGROUND: Acute rejection episodes after renal transplantation are an important
      clinical challenge, despite use of multidrug immunosuppressive regimens. We did a
      prospective, multicentre, randomised, double-blind trial to investigate the
      impact of the addition of sirolimus, compared with azathioprine, to a cyclosporin
      and prednisone regimen. METHODS: 719 recipients of primary HLA-mismatched
      cadaveric or living-donor renal allografts who displayed initial graft function
      were randomly assigned, after transplantation, sirolimus 2 mg daily (n=284) or 5
      mg daily (n=274), or azathioprine (n=161). We assessed the primary composite
      endpoint of efficacy failure, occurrence of biopsy-confirmed acute rejection
      episodes, graft loss, or death, and various secondary endpoints that characterise
      these episodes at 6 months and 12 months. Analyses were done by intention to
      treat. FINDINGS: The rate of efficacy failure at 6 months was lower in the two
      sirolimus groups (2 mg 18.7%, p=0.002; 5 mg 16.8%, p<0.001) than in the
      azathioprine group (32.3%). The frequency of biopsy-confirmed acute rejection
      episodes was also lower (2 mg 16.9%, p=0.002; 5 mg 12.0%, p<0.001; azathioprine
      29.8%). At 12 months, survival was similar in all groups for grafts (97.2%,
      96.0%, and 98.1%) and patients (94.7%, 92.7%, and 93.8%). Patients on sirolimus
      showed a delay in the time to first acute rejection episode and decreased
      frequency of moderate and severe histological grades of rejection episodes and
      related antibody treatment, compared with the azathioprine group. Rates of
      infection and malignant disorders were similar in all groups. INTERPRETATION: Use
      of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection
      episodes with no increase in complications. Further studies are needed to
      establish the optimum doses for the combined regimen.

PMID- 10963198
TI  - Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma.
      French Coeliac Disease Study Group.
AB  - BACKGROUND: Adult refractory sprue is a poorly defined disorder. We did a
      multicentre national study of patients with refractory sprue to characterise
      their clinical and pathological profile and outcome, and to assess the frequency
      and prognostic significance of phenotypic and molecular abnormalities in the
      intraepithelial T-cell population. METHODS: Patients with severe symptomatic
      villous atrophy mimicking coeliac disease but refractory to a strict gluten-free
      diet, and with no initial evidence of overt lymphoma, were diagnosed at
      gastrointestinal referral centres between 1974 and 1998. Fixed and/or frozen
      duodenojejunal biopsy samples were reanalysed and immunostained with CD3 and CD8
      monoclonal antibodies to find out the phenotype of intraepithelial lymphocytes
      (IEL). TCRgamma gene rearrangements were assessed on frozen biopsy samples by
      multiplex fluorescent PCR. FINDINGS: There were 21 patients with refractory sprue
      and 20 controls with coeliacs disease. 16 (84%) of 19 assessed patients had an
      aberrant intraepithelial lymphoid intestinal population expressing
      intracytoplasmic CD3 but not surface CD8. Clonal intestinal TCRgamma gene
      rearrangements were found in 13 (76%) of 17 patients assessed; four (out of 12
      assessed) had clonal dissemination to the blood. The 16 patients with an aberrant
      phenotype all had uncontrolled malabsorption; three subsequently developed overt
      T-cell lymphoma, and eight died. The three (16%) patients without aberrant clonal
      IEL made a complete clinical and histological recovery with steroid therapy plus
      a gluten-free diet. INTERPRETATION: An immunophenotypically aberrant clonal
      intraepithelial T-cell population (similar to that of most cases of enteropathy
      associated T-cell lymphoma) can be found in up to 75% of patients with refractory
      coeliac sprue; its identification by simple diagnostic techniques represents a
      marker of poor outcome (including occurrence of overt T-cell lymphoma). We
      suggest that refractory sprue associated with an aberrant clonal IEL may be the
      missing link between coeliac disease and T-cell lymphoma and may be classified as
      cryptic enteropathy-associated T-cell lymphoma.

PMID- 10963199
TI  - Visualisation of cell death in vivo in patients with acute myocardial infarction.
AB  - BACKGROUND: In-vivo visualisation and quantification of the extent and time-frame
      of cell death after acute myocardial infarction would be of great interest. We
      studied in-vivo cell death in the hearts of patients with an acute myocardial
      infarction using imaging with technetium-99m-labelled annexin-V-a protein that
      binds to cells undergoing apoptosis. METHODS: Seven patients with an acute
      myocardial infarction and one control were studied. All patients were treated by
      percutaneous transluminal coronary angioplasty (six primary and one rescue),
      resulting in thrombolysis in myocardial infarction (TIMI) III flow of the infarct
      related artery. 2 h after reperfusion, 1 mg annexin-V labelled with 584 MBq Tc
      99m was injected intravenously. Early (mean 3.4 h) and late (mean 20.5 h) single
      photon-emission computed tomographic (SPECT) images of the heart were obtained.
      Routine myocardial resting-perfusion imaging was also done to verify infarct
      localisation. FINDINGS: In six of the seven patients, increased uptake of Tc-99m
      labelled annexin-V was seen in the infarct area of the heart on early and late
      SPECT images. No increased uptake was seen in the heart outside the infarct area.
      All patients with increased Tc-99m-labelled annexin-V uptake in the infarct area
      showed a matching perfusion defect. In a control individual, no increased uptake
      in the heart was seen. INTERPRETATION: Increased uptake of Tc-99m-labelled
      annexin-V is present in the infarct area of patients with an acute myocardial
      infarction, suggesting that programmed cell death occurs in that area. The
      annexin-V imaging protocol might allow us to study the dynamics of reperfusion
      induced cell death in the area at risk and may help to assess interventions that
      inhibit cell death in patients with an acute myocardial infarction.

PMID- 10963200
TI  - Hereditary angioedema with normal C1-inhibitor activity in women.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a well defined autosomal dominant
      disease (Mendelian Inheritance in Man #106100) that results from an inherited
      deficiency of C1 (the activated first component of complement) inhibitor
      function. We report an unusual variant of HAE with normal biochemical C1
      inhibitor function, occurring only in women. METHODS: We screened 574 patients
      with recurrent angioedema of the skin for presence of HAE. 283 patients were
      selected, in whom angioedema was associated with abdominal pain attacks or
      recurrent life-threatening episodes of upper-airway obstruction, or both, rather
      than with urticaria. We measured C1-inhibitor concentration and functional
      activity as well as complement C4 concentration and took pedigrees to
      characterise patients. FINDINGS: 94 HAE cases with C1-inhibitor deficiency,
      positive family history, or both were identified. Biochemical testing showed that
      84 patients from 49 families had a functional C1-inhibitor deficiency. 11 of
      these patients had no affected family members (probably representing de-novo
      mutations). Ten women with HAE, from ten families, had normal C1-inhibitor
      protein concentrations and function, and normal C4 concentration. A more detailed
      study of these families identified another 26 affected members, who were also all
      women. Of those women, 14 could be studied and also had normal C1-inhibitor
      concentration and function. The disease was seen in successive generations, and
      in offspring of affected mothers, the sex ratio (M/F) was shifted to 1/1.5.
      INTERPRETATION: HAE with normal C1-inhibitor concentration and function
      represents a unique genetic disease arising only in women. The formal genetics of
      this entity are suggestive of an X-linked dominant mode of inheritance. For this
      disorder we propose the term hereditary angioedema type 3 (HAE III).

PMID- 10963201
TI  - Sheep, watercress, and the Internet.

PMID- 10963202
TI  - Pumpless extracorporeal lung assist and adult respiratory distress syndrome.
AB  - We report use of a pumpless extracorporeal lung assist-a safe and effective
      method in the management of severe acute respiratory failure that allows an
      extracorporal gas-exchange without the use of a pump.

PMID- 10963204
TI  - Affect of deep brain stimulation on limb paresis after stroke.
AB  - A deep brain stimulator was implanted in the periventricular grey matter of the
      third ventricle for pain after stroke in a man aged 48 years. As well as a
      beneficial analgesic effect, the patient reported improved function in the
      contralateral paretic arm, which was confirmed on formal testing.

PMID- 10963203
TI  - Expression analysis of classic and non-classic HLA molecules before interferon
      alfa-2b treatment of melanoma.
AB  - Individual predictive clinical, immunological, or molecular features for
      definition of patients with lymph-node-positive melanoma who do not benefit from
      adjuvant postsurgery high-dose interferon alpha treatment are lacking. Expression
      analysis of classic and non-classic HLA molecules on melanoma cells metastatic to
      the locoregional lymph node may help select these patients before treatment.

PMID- 10963205
TI  - Blood stem-cell transplantation for chronic active Epstein-Barr virus with
      lymphoproliferation.
AB  - A boy with chronic active Epstein-Barr virus infection (EBV) developed bilateral
      exophthalmos by infiltrating EBV-infected natural-killer cells during combined
      chemotherapy. This unusual presentation resolved completely after allogeneic bone
      marrow transplantation, and EBV-infected peripheral T and natural-killer cells
      were also eradicated.

PMID- 10963206
TI  - Mbeki defiant about South African HIV/AIDS strategy.

PMID- 10963207
TI  - Male circumcision could help protect against HIV infection.

PMID- 10963208
TI  - Future uncertain for reliable vCJD screening tests.

PMID- 10963209
TI  - Arming the population against polio in Somalia.

PMID- 10963210
TI  - Malaysia culls pigs as Nipah virus strikes again.

PMID- 10963211
TI  - India raises standards for traditional drugs.

PMID- 10963212
TI  - The importance of selenium to human health.
AB  - The essential trace mineral, selenium, is of fundamental importance to human
      health. As a constituent of selenoproteins, selenium has structural and enzymic
      roles, in the latter context being best-known as an antioxidant and catalyst for
      the production of active thyroid hormone. Selenium is needed for the proper
      functioning of the immune system, and appears to be a key nutrient in
      counteracting the development of virulence and inhibiting HIV progression to
      AIDS. It is required for sperm motility and may reduce the risk of miscarriage.
      Deficiency has been linked to adverse mood states. Findings have been equivocal
      in linking selenium to cardiovascular disease risk although other conditions
      involving oxidative stress and inflammation have shown benefits of a higher
      selenium status. An elevated selenium intake may be associated with reduced
      cancer risk. Large clinical trials are now planned to confirm or refute this
      hypothesis. In the context of these health effects, low or diminishing selenium
      status in some parts of the world, notably in some European countries, is giving
      cause for concern.

PMID- 10963213
TI  - Evolutionary adaptation of inflammatory immune responses in human beings.
AB  - Modern man's ancestors lived in an environment where infectious, tropical
      diseases would have been endemic. We postulate that this relatively hostile
      environment would have caused genetic selection for increased proinflammatory
      immune responses. On migrating to temperate regions, pronounced proinflammatory
      responses would have been less important and selected against due to increased
      mortality from overly vigorous responses to harmless environmental agents. This
      hypothesis is supported by the observation that proinflammatory alleles in
      several genes involved in inflammation are more prevalent in populations with
      long-term tropical ancestry than those with long-term residence in temperate
      regions. In addition, when the former populations relocate from a tropical to a
      temperate region, they have a higher incidence of allergic inflammatory diseases
      than the latter populations. These observations suggest that there may be general
      patterns of recent evolutionary adaptation of the human immune system to
      particular regions and that these adaptations can produce differences in disease
      susceptibility.

PMID- 10963214
TI  - Medical migration: who are the real losers?

PMID- 10963216
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963215
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963217
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963218
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963219
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963220
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963221
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963222
TI  - PEP trial. Pulmonary Embolism Prevention.

PMID- 10963223
TI  - Acquired anaemia and polycythaemia.

PMID- 10963225
TI  - Antipsychotic drugs and venous thromboembolism.

PMID- 10963224
TI  - Antipsychotic drugs and venous thromboembolism.

PMID- 10963226
TI  - Antipsychotic drugs and venous thromboembolism.

PMID- 10963227
TI  - MRI and the second French case of vCJD.

PMID- 10963228
TI  - G protein in very low birth-weight infants.

PMID- 10963229
TI  - Information on thiazolidinediones.

PMID- 10963230
TI  - Recognising lesions on colonoscopy.

PMID- 10963231
TI  - Phenobarbital for children with cerebral malaria.

PMID- 10963232
TI  - Chernobyl-induced radiophobia and the incidence of tuberculosis.

PMID- 10963233
TI  - Not so inefficient reproduction.

PMID- 10963234
TI  - Skull fracture--child abuse or an accident?

PMID- 10963235
TI  - The Nobel chronicles. 1997: Stanley Ben Prusiner (b 1942).

PMID- 10963236
TI  - Making sense of genome mania.

PMID- 10963237
TI  - What if we had an AIDS vaccine?

PMID- 10963238
TI  - HIV voluntary counselling and testing in community health services.

PMID- 10963239
TI  - Therapeutic implications of non-genomic glucocorticoid activity.

PMID- 10963240
TI  - Mono-ocular occlusion for treatment of dyslexia.

PMID- 10963241
TI  - Patient-triggered ventilation of the newborn.

PMID- 10963242
TI  - Impact of screening old people with physical illness for depression?

PMID- 10963243
TI  - A votre sante?

PMID- 10963244
TI  - Effect of a surgical training programme on outcome of rectal cancer in the County
      of Stockholm. Stockholm Colorectal Cancer Study Group, Basingstoke Bowel Cancer
      Research Project.
AB  - BACKGROUND: The Stockholm I and II randomised trials demonstrated the value of
      preoperative radiotherapy in preventing local recurrence in rectal cancer. This,
      study investigated the potential for further improvement by introduction of the
      concept of total mesorectal excision (TME) to surgeons in Stockholm, Sweden.
      METHODS: Workshops started in 1994 and included 11 television-based
      demonstrations and two histopathology sessions. The study population consisted of
      all patients who underwent abdominal operations for rectal cancer in Stockholm
      County during 1995-96 (TME project; n=447). Outcomes at 2 years were compared
      with those from the Stockholm I (n=790) and II (n=542) trials as historical
      controls. FINDINGS: For patients with curative abdominal resections, there were
      no differences between the Stockholm I (n=686), Stockholm II (n=481), and TME
      project (n=381) groups in 30-day mortality (30 [4%], six [1%], and 12 [3%]),
      anastomotic leakage (27 [10%], 18 [9%], and 23 [9%]), or all complications (204
      [30%], 169 [35%], and 134 [35%]). This similarity was achieved despite a decrease
      in the proportion of abdominoperineal procedures from 55-60% to 27%. Local
      recurrence occurred in significantly fewer of the TME group than of the Stockholm
      I and II groups (21 [6%] vs 103 [15%] and 66 [14%], p<0.001) as did cancer
      related death (35 [9%] vs 104 [15%] and 77 [16%], p<0.002). INTERPRETATION: A
      surgical teaching initiative had a major effect on cancer outcomes. The
      proportion of abdominoperineal procedures and the local recurrence rate decreased
      by more than 50% and there is already evidence of a decline in rectal-cancer
      mortality.

PMID- 10963245
TI  - Oral anticoagulation self-management and management by a specialist
      anticoagulation clinic: a randomised cross-over comparison.
AB  - BACKGROUND: Vitamin K antagonist treatment is effective for prevention and
      treatment of thromboembolic events but frequent laboratory control and dose
      adjustment are essential. Small portable devices have enabled patient self
      monitoring of anticoagulation and self-adjustment of the dose. We compared this
      self-management of oral anticoagulant therapy with conventional management by a
      specialist anticoagulation clinic in a randomised cross-over study. METHODS: 50
      patients on long-term oral anticoagulant treatment were included in a randomised
      controlled crossover study. Patients were self-managed or were managed by the
      anticoagulation clinic for a period of 3 months. After this period the
      alternative strategy was followed for each patient. Prothrombin time (expressed
      as international normalised ratio [INR]) were measured at intervals of 1-2 weeks
      in both periods without knowledge of type of management. The primary endpoint was
      the number of measurements within the therapeutic range (therapeutic target value
      +/-50.5 INR units). FINDINGS: There was no significant difference in the overall
      quality of control of anticoagulation between the two study periods. Patients
      were for 55% and for 49% of the treatment period within a range of +/-0.5 from
      the therapeutic target INR during self-management and anticoagulation clinic
      management, respectively (p=0.06). The proportion of patients who spent most time
      in the therapeutic target range was larger during self-management than during
      anticoagulation clinic-guided management. The odds ratio for a better control of
      anticoagulation (defined as the period of time in the therapeutic target range)
      during self-management compared with anticoagulation clinic-guided management was
      4.6 (95% CI 2.1-10.2). A patient-satisfaction assessment showed superiority of
      self-management over conventional care. INTERPRETATION: Self-management of INR in
      the population in this study is feasible and appears to result in control of
      anticoagulation that is at least equivalent to management by a specialist
      anticoagulation clinic. It is also better appreciated by patients. Larger studies
      are required to assess the effect of this novel management strategy on the
      incidence of thromboembolic or bleeding complications.

PMID- 10963246
TI  - Efficacy of voluntary HIV-1 counselling and testing in individuals and couples in
      Kenya, Tanzania, and Trinidad: a randomised trial. The Voluntary HIV-1 Counseling
      and Testing Efficacy Study Group.
AB  - BACKGROUND: Our aim was to determine the efficacy of HIV-1 voluntary counselling
      and testing (VCT) in reducing unprotected intercourse among individuals and sex
      partner couples in Nairobi (Kenya), Dar es Salaam (Tanzania), and Port of Spain
      (Trinidad). METHODS: Individual or couple participants were randomly assigned HIV
      1 VCT or basic health information. At first follow-up (mean 7.3 months after
      baseline) health-information participants were offered VCT and all VCT
      participants were offered retesting. Sexually transmitted infections were
      diagnosed and treated at first follow-up. The second follow-up (mean 13.9 months
      after baseline) involved only behavioural assessment, and all participants were
      again offered VCT. FINDINGS: 3120 individuals and 586 couples were enrolled. The
      proportion of individuals reporting unprotected intercourse with non-primary
      partners declined significantly more for those receiving VCT than those receiving
      health information (men, 35% reduction with VCT vs 13% reduction with health
      information; women, 39% reduction with VCT vs 17% reduction with health
      information), and these results were maintained at the second follow-up.
      Individual HIV-1-infected men were more likely than uninfected men to reduce
      unprotected intercourse with primary and non-primary partners, whereas HIV-1
      infected women were more likely than uninfected women to reduce unprotected
      intercourse with primary partners. Couples assigned VCT reduced unprotected
      intercourse with their enrolment partners significantly more than couples
      assigned health information, but no differences were found in unprotected
      intercourse with non-enrolment partners. Couples in which one or both members
      were diagnosed with HIV-1 were more likely to reduce unprotected intercourse with
      each other than couples in which both members were uninfected. These changes were
      replicated by those in the health-information group diagnosed with HIV-1 at first
      follow-up. INTERPRETATION: These data support the efficacy of HIV-1 VCT in
      promoting behaviour change.

PMID- 10963248
TI  - Depression after stroke and lesion location: a systematic review.
AB  - BACKGROUND: There is conflicting evidence on the hypothesis that the risk of
      depression after stroke is influenced by the location of the brain lesion. We
      undertook a systematic review to examine the hypotheses that depression is more
      commonly associated with left-hemisphere strokes than with right-hemisphere
      strokes and with lesions of the left anterior brain than with other regions.
      METHODS: We did a computer-aided search of MEDLINE, BIDS ISI, and PsychLit
      databases supplemented by hand searches of key journals. We included all reports
      on the association of depression after stroke with the location of the brain
      lesion. Studies were systematically and independently examined by two
      investigators. Fixed-effects and random-effects meta-analyses were done.
      FINDINGS: 143 reports were identified by the search strategy. 48 were eligible
      for inclusion. Not all reports included original data. Only two reports of
      original data supported the hypotheses and seven clearly did not. The pooled
      (random-effects) relative risk of depression after a left-hemisphere stroke,
      compared with a right-hemisphere stroke, was 0.95 (95% CI 0.83-1.10). For
      depression after a left anterior lesion compared with all other brain areas the
      pooled (random-effects) relative risk was 1-17 (0.87-1.62). Restriction of the
      analyses to reports from high-quality studies or major depressive disorder did
      not substantially affect the findings. Nor were they affected by stratification
      of the time between stroke and the assessment of depression. Multiple
      publications from the same samples of patients were apparent. INTERPRETATION:
      This systematic review offered no support for the hypothesis that the risk of
      depression after stroke is affected by the location of the brain lesion.

PMID- 10963247
TI  - Cost-effectiveness of voluntary HIV-1 counselling and testing in reducing sexual
      transmission of HIV-1 in Kenya and Tanzania.
AB  - BACKGROUND: Access to HIV-1 voluntary counselling and testing (VCT) is severely
      limited in less-developed countries. We undertook a multisite trial of HIV-1 VCT
      to assess its impact, cost, and cost-effectiveness in less-developed country
      settings. METHODS: The cost-effectiveness of HIV-1 VCT was estimated for a
      hypothetical cohort of 10000 people seeking VCT in urban east Africa. Outcomes
      were modelled based on results from a randomised controlled trial of HIV-1 VCT in
      Tanzania and Kenya. Our main outcome measures included programme cost, number of
      HIV-1 infections averted, cost per HIV-1 infection averted, and cost per
      disability-adjusted life-year (DALY) saved. We also modelled the impact of
      targeting VCT by HIV-1 prevalence of the client population, and the proportion of
      clients who receive VCT as a couple compared with as individuals. Sensitivity
      analysis was done on all model parameters. FINDINGS: HIV-1 VCT was estimated to
      avert 1104 HIV-1 infections in Kenya and 895 in Tanzania during the subsequent
      year. The cost per HIV-1 infection averted was US$249 and $346, respectively, and
      the cost per DALY saved was $12.77 and $17.78. The intervention was most cost
      effective for HIV-1-infected people and those who received VCT as a couple. The
      cost-effectiveness of VCT was robust, with a range for the average cost per DALY
      saved of $5.16-27.36 in Kenya, and $6.58-45.03 in Tanzania. Analysis of targeting
      showed that increasing the proportion of couples to 70% reduces the cost per DALY
      saved to $10.71 in Kenya and $13.39 in Tanzania, and that targeting a population
      with HIV-1 prevalence of 45% decreased the cost per DALY saved to $8.36 in Kenya
      and $11.74 in Tanzania. INTERPRETATION: HIV-1 VCT is highly cost-effective in
      urban east African settings, but slightly less so than interventions such as
      improvement of sexually transmitted disease services and universal provision of
      nevirapine to pregnant women in high-prevalence settings. With the targeting of
      VCT to populations with high HIV-1 prevalence and couples the cost-effectiveness
      of VCT is improved significantly.

PMID- 10963249
TI  - Novel technique for three-dimensional visualisation and quantification of
      deformable, moving soft-tissue body parts.
AB  - BACKGROUND: Three-dimensional (3D) imaging of delicate, moving soft-tissue body
      parts is very difficult. Our understanding of the muscles that control lip
      movements is based largely on histological and cadaveric studies, which provide
      scant information about dynamic morphology. Our aim was to develop an innovative
      scanning technique for the imaging and reconstruction of dynamic orofacial
      morphology by use of 3D and four-dimensional (4D, ie, 3D plus time)
      ultrasonography. METHODS: Four volunteers (including one patient) underwent
      ultrasonography with 3D/4D imaging systems. To avoid deformation of the delicate
      orofacial structures, a water bath with an acoustic window was devised. The
      orofacial part was immersed in the bath throughout scanning, and a timer was used
      to synchronize lip movements with the 4D scan. FINDINGS: 4D views showed the
      functional differences in superficial and deep muscle groups of the lips, and
      clearly showed the changes occurring with movement of the lips and mouth. In the
      patient, a pathological layer and its extension corresponding to surface
      malformation were clearly identified. INTERPRETATION: We have developed a
      prototype device that has made possible 3D and 4D examination of orofacial
      anatomy and function. With further refinement of the device and improvement in 4D
      acquisition timing, this technique may offer a new way of dynamically imaging and
      quantifying many soft-tissue parts in 3D without deforming structure or
      disturbing function.

PMID- 10963250
TI  - A baby with bulging anterior fontanelle.

PMID- 10963251
TI  - Risk and aetiology of diarrhoea at various tourist destinations.
AB  - Almost two of three tourists developed traveller's diarrhoea during 2-week stays
      at high-risk destinations. Large differences in infection rates between hotels
      were seen. Patients with milder forms of diarrhoea show a similar chronology to
      those more severely affected. Although enterotoxigenic Escherichia coil was the
      most frequent cause, viral pathogens were detected more often than in other
      studies.

PMID- 10963252
TI  - Voltage-gated potassium channels in human ductus arteriosus.
AB  - We studied tone in the human ductus arteriosus and show that the constriction to
      oxygen is due to inhibition of voltage-gated potassium channels and, in the acute
      phase, is independent of endothelin-1.

PMID- 10963253
TI  - Female genital mutilation in eastern Ethiopia.
AB  - In Ethiopians at large, women and men are caught in a vicious circle of erroneous
      expectations and a mute consensus that maintains female genital mutilation (FGM).
      We have shown clear signs of erosion of this practice and the potential for
      further influence and change.

PMID- 10963254
TI  - E-mail consultations in international health.
AB  - We describe an e-mail health-consultation service for overseas volunteers that
      has been in operation for 25 months. The scheme is accessed for diverse medical
      concerns and is efficient and highly valued.

PMID- 10963255
TI  - Bigger and better tobacco warning labels.

PMID- 10963256
TI  - Web gears up for people with disabilities.

PMID- 10963257
TI  - Launching a lymphatic filariasis campaign in the Pacific Islands.

PMID- 10963258
TI  - United Nations calls for more effort into equal human rights.

PMID- 10963259
TI  - GMC's sifting and investigation of complaints must be "transparent".

PMID- 10963260
TI  - Premature cardiovascular disease in chronic renal failure.
AB  - There is a remarkable lack of reliable information about the determinants of risk
      of cardiovascular disease (CVD) among patients with chronic renal failure.
      Indeed, such patients have often been deliberately excluded from randomised
      trials of treatments of CVD, perhaps because of concerns about drug safety. But
      the absolute risk of CVD among them may be large, so the potential absolute
      benefits of treatments may also be large, and may well exceed any increased
      hazards. Hence, as well as further investigation of the underlying mechanisms of
      cardiac disease, it would be helpful to have some large-scale randomised trials
      in a wide range of renal patients of interventions (such as cholesterol-lowering
      drugs, antihypertensives, aspirin, B-vitamins, and antioxidant vitamins) that are
      of proven or suspected benefit in other settings. If safe and effective
      treatments can be identified, and started early in the natural history of renal
      failure, the exceptionally high risk of CVD experienced by these patients could
      be decreased before and after end-stage renal failure has occurred.

PMID- 10963261
TI  - A conversation with the leaders of the Gates Foundation's Global Health Program:
      Gordon Perkin and William Foege.
AB  - Over the past 3 years, the Bill & Melinda Gates Foundation has committed more
      than $1.7 billion to help prevent and eradicate diseases that afflict people
      living in the world's poorest nations. The gifts have revitalized a number of
      major global health initiatives that in recent years had lost momentum and helped
      to refocus the world's attention on the health crises facing many developing
      nations.

PMID- 10963262
TI  - Professionalism: an ideal to be sustained.

PMID- 10963263
TI  - The MMR question.

PMID- 10963264
TI  - The MMR question.

PMID- 10963265
TI  - The MMR question.

PMID- 10963266
TI  - The MMR question.

PMID- 10963267
TI  - The MMR question.

PMID- 10963268
TI  - Role of sleep apnoea in epilepsy in elderly people.

PMID- 10963269
TI  - Imaging hypnotic paralysis.

PMID- 10963271
TI  - Alosetron in irritable bowel syndrome.

PMID- 10963270
TI  - Mycophenolate mofetil in Crohn's disease.

PMID- 10963272
TI  - Still life in oxidation hypothesis of atherogenesis.

PMID- 10963273
TI  - Still life in oxidation hypothesis of atherogenesis.

PMID- 10963274
TI  - Still life in oxidation hypothesis of atherogenesis.

PMID- 10963275
TI  - Combating medical errors.

PMID- 10963276
TI  - Combating medical errors.

PMID- 10963277
TI  - Pumactant and poractant alfa surfactant treatment.

PMID- 10963278
TI  - Screening for sickle-cell disease in Brazil.

PMID- 10963279
TI  - Erectile dysfunction with chemotherapy.

PMID- 10963280
TI  - Proposal of an international case-report database.

PMID- 10963281
TI  - Arsenics and old places.

PMID- 10963282
TI  - The Nobel chronicles. 1996: Peter Charles Doherty (b 1940) and Rolf M Zinkernagel
      (b 1944).

PMID- 10963283
TI  - The proton-pump inhibitors: similarities and differences.
AB  - OBJECTIVE: This paper examines the clinical pharmacology of the proton-pump
      inhibitors (PPIs) and briefly reviews some comparative studies of these agents.
      BACKGROUND: PPIs have emerged as the treatment of choice for acid-related
      diseases, including gastroesophageal reflux disease (GERD) and peptic ulcer
      disease. Although these drugs-omeprazole, lansoprazole, pantoprazole, and
      rabeprazole-share a common structure (all are substituted benzimidazoles) and
      mode of action (inhibition of H+,K+-adenosine triphosphatase [ATPase]), each
      differs somewhat in its clinical pharmacology. RESULTS: In comparative clinical
      trials found in MEDLINE, PPIs administered once daily produced endoscopic
      evidence of healing in >90% of patients with duodenal ulcer after 4 weeks of
      treatment, in >90% of those with gastric ulcer after 6 weeks of treatment, and in
      >90% of those with ulcerative or erosive GERD after 8 weeks of treatment.
      Maintenance therapy with daily doses of a PPI has been shown to be an effective
      means of preventing GERD relapse. PPIs also inhibit the growth of Helicobacter
      pylori, now recognized as an important factor in peptic ulcer disease, and, when
      administered in combination with antibiotics, provide the best treatment for
      eradication of the bacterium. Rabeprazole has a more rapid onset of H+,K+-ATPase
      inhibition than the other PPIs and, compared with omeprazole, a greater effect on
      intragastric pH after the first dose. Omeprazole and lansoprazole have a greater
      potential for drug-drug interactions than do pantoprazole and rabeprazole.
      CONCLUSION: Although the individual PPIs have similar efficacy in many cases,
      differences between them should be considered when choosing a treatment regimen.

PMID- 10963284
TI  - Clarithromycin in the management of community-acquired pneumonia.
AB  - OBJECTIVE: To review the epidemiology and diagnosis of community-acquired
      pneumonia (CAP) and examine factors that influence the choice of empiric
      antimicrobial therapy. BACKGROUND: CAP remains a common disease with substantial
      associated morbidity and mortality. Outpatient management of patients with CAP
      has become increasingly complex because of the availability of newer
      antimicrobial agents, evolving patterns of resistance, and the increasing
      recognition of atypical pathogens. Although Streptococcus pneumoniae remains a
      commonly encountered pathogen, the development and increasing prevalence of
      antibiotic resistance has become an area of concern, especially in outpatients.
      The newer macrolide antimicrobial drugs-clarithromycin and azithromycin-are
      effective against commonly encountered pathogens, are well tolerated, and have an
      established tolerability profile, although the low serum levels achieved by
      azithromycin hinder its use in patients with suspected bacteremia. METHODS: A
      MEDLINE search was performed of English-language articles published from 1990 to
      2000 on the treatment of CAP. This article reviews the treatment of CAP, with
      emphasis on the use of clarithromycin. CONCLUSION: Although laboratory
      surveillance studies have reported macrolide-resistant S. pneumoniae, recent
      evidence defining the mechanism of this resistance, coupled with the
      pharmacokinetic properties of the macrolide agents, suggests that the actual rate
      of clinical macrolide resistance is low.

PMID- 10963285
TI  - Challenges in the development of an effective HIV vaccine: current approaches and
      future directions.
AB  - OBJECTIVE: The intent of this review is to investigate and discuss why developing
      a successful HIV vaccine has been so challenging, first by examining the
      molecular biology of the virus and how HIV interacts with the immune system, and
      then reviewing past viral vaccine successes as well as future directions for HIV
      vaccine research. BACKGROUND: Since HIV appeared in the United States in the
      early 1980s, an estimated 40 million people worldwide have been infected with the
      virus. Despite promising advances in the pharmacotherapy of HIV infection, it is
      apparent that the best, most cost-effective strategy for controlling the further
      spread of the virus is through synthesis of a protective vaccine. Almost 2
      decades into the epidemic, there are few prospects for a truly effective vaccine
      entering the market in the foreseeable future. METHODS: MEDLINE was searched for
      articles written between 1966 and June 1999. Search terms used were AIDS, HIV
      vaccine, HIV-1, HIV-2, vaccines, and human immunodeficiency virus. RESULTS: Only
      2 candidates for an HIV vaccine are currently in phase III clinical trials (1 in
      the United States and 1 in Thailand). The efficacy of these vaccines when applied
      to the population as a whole is widely questioned, largely because they induce
      protection by an antibody response only. Several studies have suggested that this
      approach will likely be ineffective in providing any real protection from viral
      infection. It appears that a strong cellular immune response is necessary in
      addition to a strong antibody response.

PMID- 10963286
TI  - Safety and immunogenicity profile of a recombinant outer-surface protein A Lyme
      disease vaccine: clinical trial of a 3-dose schedule at 0, 1, and 2 months.
AB  - OBJECTIVES: This study compared the tolerability of a Lyme disease vaccine
      administered intramuscularly at 0 and 1 months with that of a vaccine
      administered at 0, 1, and 2 months to determine (1) whether adding a third dose
      of vaccine 1 month after the second would affect the safety profile, and (2)
      whether a shortened vaccination schedule of 0, 1, and 2 months would provide an
      immune response similar to that obtained with vaccine administered at 0, 1, and
      12 months. BACKGROUND: An efficacy trial of a Lyme disease vaccine had
      demonstrated safety and efficacy against definite (clinically manifested and
      laboratory-confirmed) Lyme disease after 3 doses at 0, 1, and 12 months and
      resulted in 90% of subjects having titers > or =1400 enzyme-linked immunosorbent
      assay units (EL.U)/mL (the proposed seroprotective level for 1 tick season).
      METHODS: This multicenter, open-label, prospective, randomized study assessed the
      safety and efficacy of different doses of a recombinant outer-surface protein A
      (OspA) vaccine in 956 volunteers aged 17 to 72 years from 3 Lyme disease-endemic
      sites. Blood samples were collected at months 0, 2, 3, 12, and 13 to assess total
      immunoglobulin-G anti-OspA titers. RESULTS: Most adverse events were transient
      and mild to moderate. The geometric mean antibody titer increased 2.8-fold from
      month 2 (1786 EL.U/mL to 4842 EL.U/mL), and approximately 90% of the volunteers
      had a titer > or =1400 and 99% had a titer > or =400 EL.U/mL (the mini- mum
      seroprotective level at any given time) after the third dose. An antibody
      kinetics model predicts that protection would last for a typical tick
      transmission season. CONCLUSIONS: In volunteers aged 17 to 72 years, 3 doses of
      vaccine administered in 2 months was well tolerated, more immunogenic than 2
      doses, and provided a higher probability of protection before exposure or travel
      to Lyme disease-endemic areas.

PMID- 10963287
TI  - Effectiveness of specific immunotherapy in the treatment of asthma: a meta
      analysis of prospective, randomized, double-blind, placebo-controlled studies.
AB  - BACKGROUND: Despite decades of positive experience with specific immunotherapy
      (SIT) in the treatment of asthma, outcomes associated with SIT have not been
      evaluated. OBJECTIVE: This meta-analysis was conducted to compare the effects of
      SIT plus medical treatment with those of SIT without medical treatment in
      patients with asthma. METHODS: All studies of SIT in patients with asthma
      published in English between the years 1966 and 1998 were identified through a
      MEDLINE search. All prospective, randomized, double-blind, placebo-controlled
      studies of SIT identified by the search were included in the meta-analysis. One
      author (R.N.R.) extracted data from these studies. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated using a random-effects model. RESULTS:
      Data were extracted from 24 identified studies of the clinical effectiveness of
      SIT in the treatment of asthma, involving 962 asthmatic patients with documented
      allergy. Immunotherapy was judged effective in 17 (71%) of the 24 studies,
      ineffective in 4 (17%), and equivocal in 3 (12%) (chi2 = 15.25, df = 2, P =
      0.0005). Symptoms of asthma were more likely to improve in patients who received
      SIT than in patients who received placebo (OR 2.76, 95% CI 2.22 to 3.42). Results
      also favored the immunotherapy group for improvement in pulmonary function (OR
      2.87, 95% CI 1.82 to 4.52), protection against bronchial challenge (OR 1.81, 95%
      CI 1.32 to 2.49), and reduced need for medications (OR 2.00, 95% CI 1.46 to
      2.72). CONCLUSION: The findings of this meta-analysis support the conclusion that
      SIT is effective in a population of patients with allergen-triggered asthma.

PMID- 10963288
TI  - Effectiveness of specific immunotherapy in the treatment of allergic rhinitis: an
      analysis of randomized, prospective, single- or double-blind, placebo-controlled
      studies.
AB  - BACKGROUND: The effectiveness of specific immunotherapy (SIT) in the treatment of
      allergic rhinitis has been supported by empirical evidence and clinical
      experience. OBJECTIVE: This report is an analysis of multiple studies involving
      patients with documented allergic rhinitis. METHODS: All studies of the
      effectiveness of SIT in the treatment of allergic rhinitis published in English
      between the years 1966 and 1996 were identified through a MEDLINE search. All
      prospective, single- or double-blind, placebo-controlled studies were included in
      the analysis. One author (R.N.R.) extracted data from the studies. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects
      model for a variety of clinical measures in studies that permitted the extraction
      of numbers of patients with positive and negative outcomes. RESULTS: Data were
      extracted from 16 studies of the clinical effectiveness of SIT in the treatment
      of allergic rhinitis, involving 759 patients (546 adults, 53 children, 160 all
      ages). In 15 (94%) of the studies, investigators concluded that SIT was
      effective. In the remaining study (the only one conducted in children),
      investigators concluded that SIT was not effective. Symptoms of allergic rhinitis
      were more likely to improve in patients receiving SIT than in the comparison
      patients (OR 1.81, 95% CI 1.48 to 2.23). Symptom-medication scores were
      significantly lower in patients receiving SIT than in the comparison patients in
      all studies using such measures (P < 0.05). CONCLUSION: Results of this analysis
      support the conclusion that SIT is effective in the treatment of allergic
      rhinitis.

PMID- 10963289
TI  - Effectiveness of specific immunotherapy in the treatment of hymenoptera venom
      hypersensitivity: a meta-analysis.
AB  - BACKGROUND: For most people, Hymenoptera stings produce a transient, local
      inflammatory reaction (pain, redness, swelling). However, for those who are
      allergic to components of this venom, the reactions can be severe, frightening,
      and sometimes fatal. Specific immunotherapy (SIT) has been the only means of
      desensitizing patients who have experienced a systemic reaction to this venom.
      OBJECTIVE: This meta-analysis was conducted to compare the effects of SIT in the
      treatment of Hymenoptera venom hypersensitivity. METHODS: All studies of SIT in
      the treatment of Hymenoptera venom hypersensitivity published in English between
      the years 1966 and 1996 were identified through a MEDLINE search. Because of the
      ethical difficulties involved in designing a double-blind, placebo-controlled
      study in this patient population, most of the studies were open and not placebo
      controlled. One author (R.N.R.) extracted data from the studies. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects
      model. RESULTS: Data were extracted from 8 studies involving 453 patients; 1
      study was conducted in adults (n = 20), 2 in children (n = 188), and 5 in all
      ages (n = 245). The symptoms of Hymenoptera venom hypersensitivity were prevented
      in 80 (79%) of the 101 patients receiving SIT versus 49 (36%) of 136 comparison
      patients. The symptoms were not prevented in 21 (21%) of the patients receiving
      SIT versus 87 (64%) of the comparison patients (OR 2.20, 95% CI 1.72 to 2.81).
      CONCLUSION: The findings of this meta-analysis support the conclusion that SIT is
      effective in the treatment of Hymenoptera venom hypersensitivity.

PMID- 10963290
TI  - Aspirin plus extended-release dipyridamole or clopidogrel compared with aspirin
      monotherapy for the prevention of recurrent ischemic stroke: a cost-effectiveness
      analysis.
AB  - OBJECTIVE: The goal of this health economic analysis was to asses the cost
      effectiveness of a fixed combination of aspirin plus extended-release
      dipyridamole (ASA/ER-DP) or clopidogrel compared with ASA monotherapy for
      prevention of recurrent ischemic stroke. BACKGROUND: The second European Stroke
      Prevention Study (ASA/ESPS-2), a large-scale clinical trial, demonstrated that a
      new therapy--a fixed combination of ASA/ER-DP--is more effective than ASA
      monotherapy for the prevention of recurrent ischemic stroke. METHODS: We used
      data from ESPS-2 to create a health economic model that estimates the incremental
      cost and cost-effectiveness of ASA/ER-DP during the 2-year time frame after an
      ischemic stroke. The model was developed from a payor perspective. The analysis
      used direct cost estimates for stroke from a Medicare claims database analysis.
      Efficacy data were obtained from clinical trials to determine the incremental
      cost per stroke averted for ASA/ER-DP or clopidogrel versus ASA. Sensitivity
      analyses also were conducted to test the reliability and robustness of the model.
      RESULTS: The results of the analysis demonstrated that ASA/ER-DP was cost
      effective compared with ASA monotherapy for the secondary prevention of stroke,
      with a cost-effectiveness ratio of $28,472. The model remained robust over a
      range of assumptions and cost estimates. Clopidogrel, however, was not cost
      effective compared with ASA (cost per stroke averted, $161,316) in either the
      base-case analysis or any of the sensitivity analyses. CONCLUSION: ASA/ER-DP thus
      offers a cost-effective alternative to ASA monotherapy for the prevention of
      recurrent ischemic stroke.

PMID- 10963291
TI  - Role of reactive oxygen species in the regulation of physiological functions.
AB  - Bio-organisms possess numerous systems that produce reactive oxygen species
      (ROS). Severe oxidative stress induces cellular damage that can lead to apoptosis
      or necrosis, but moderate ROS levels constitute and modulate normal and critical
      physiological pathways in the regulation of cellular functions, including
      signaling cascades and transcriptional/post-transcriptional control of gene
      expression. ROS are also found to mimic some of the physiological stimuli by
      direct modification of factors or indirect mechanisms via change in the oxidative
      and reductive status inside/outside cells. This review will describe the
      biological relevance and essential roles of ROS in animal cells, focusing on
      signal transduction, gene expression, apoptosis and aging.

PMID- 10963293
TI  - Preparation of specific antisera to digoxin by using digoxin C-3' and C-3"
      hemisuccinate-bovine serum albumin conjugates.
AB  - The preparation and antigenic properties of digoxin C-3' and C-3" hemisuccinate
      bovine serum albumin (BSA) conjugates are described. The antisera were prepared
      by immunizing rabbits with each of the digoxin-BSA conjugates, and properties of
      the antisera were characterized by RIA with 3H-labeled digoxin. The antidigoxin
      antiserum from immunization with digoxin 3'-hemisuccinate-BSA conjugate possessed
      high specificity for digoxin, exhibiting fairly low cross-reactions with
      dihydrodigoxin (2.1%), digoxigenin monodigitoxoside (0.9%), digoxigenin
      bisdigitoxoside (0.6%), and digoxigenin (0.1%).

PMID- 10963292
TI  - Determination of serum concentrations of glycyrrhizin in humans by semi-micro
      high-performance liquid chromatography after administration of a therapeutic
      dose.
AB  - A simple and sensitive semi-micro high-performance liquid chromatography (HPLC)
      was established for determining the serum levels of glycyrrhizin (GL) in humans.
      Butyl p-hydroxybenzoate was used as the internal standard and serum was
      deproteinized by methanol. The samples were separated on a Capcell Pak C18 UG120
      column (150 x 1.5 mm i.d.; particle size, 5 microm). The detection limit of GL in
      serum was 100 ng/ml, which enables determination of serum levels of GL after
      administration of a therapeutic dose. The time-course study suggested that the
      elimination rate of GL differed between subjects for the same administered dose,
      although the sample was too small to allow a meaningful comment. In clinical
      practice, GL is used for its antiviral and anti-inflammatory effects. Excessive
      administration of GL can induce pseudoaldosteronism; however the optimal GL
      concentration in serum remains to be determined. The determination method
      reported here is expected to aid in the safe and efficient use of the drug in
      clinical practice.

PMID- 10963294
TI  - Development of ELISAs for irinotecan and its active metabolite SN-38.
AB  - Two highly sensitive and specific enzyme-linked immunosorbent assays (ELISAs) for
      the determination of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy
      camptothecin (irinotecan) and 7-ethyl-10-hydroxycamptothecin (SN-38), an active
      metabolite of irinotecan, were developed, which are capable of measuring as low
      as 16 and 160 pg of each drug/ml, respectively. Anti-irinotecan antibody was
      obtained by immunizing rabbits with irinotecan conjugated with mercaptosuccinyl
      bovine serum albumin (MS.BSA) using N-(4-diazophenyl)maleimide (DPM) as a
      heterobifunctional coupling agent. An enzyme marker was similarly prepared by
      coupling irinotecan with horseradish peroxidase (HRP) via DPM. This ELISA for
      irinotecan was specific for irinotecan and showed almost no cross-reactivity with
      its active metabolite SN-38. Anti-SN-38 antibody was obtained by immunizing
      rabbits with SN-38 conjugated with BSA using the N-succinimidyl ester method. An
      enzyme marker was prepared by coupling SN-38 with HRP employing DPM. The ELISA
      for SN-38 was specific to SN-38 and showed a very slight cross-reactivity with
      irinotecan (0.08%). Using the 2 assays, we reconfirmed the rapid metabolite of
      irinotecan with rat serum. The 2 ELISAs may be a valuable tool for studies of the
      pharmacokinetics and pharmacodynamics of these drugs.

PMID- 10963295
TI  - A carbonyl reductase-catalyzing reduction of N3-phenacyluridine in rabbit liver.
AB  - Carbonyl reductase activity for a novel hypnotic, N3-phenacyluridine, was mainly
      localized in the cytosol fraction of rabbit liver. The enzyme (N3-phenacyluridine
      reductase) which catalyzes the reduction of N3-phenacyluridine to N3-alpha
      hydroxy-beta-phenethyluridine was purified from the cytosolic fraction of rabbit
      liver by various chromatographic techniques (DEAE-Sephacel, Red Sepharose CL-6B
      and hydroxylapatite). N3-Phenacyluridine reductase had a minimum molecular weight
      of 39kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis. This
      enzyme required reduced nicotinamide adenine dinucleotide phosphate (NADPH) as a
      cofactor and its optimal pH was 7.5. Flavonoids (quercetin and quercitrin) were
      potent inhibitors of the enzyme, but pyrazole or barbital had little effect. The
      apparent Km and Vmax values of the enzyme for the reduction of N3-phenacyluridine
      were 0.32 mM and 8.7 units/mg protein, respectively. A variety of carbonyl
      compounds, including N3-phenacyluridine, were effectively reduced by the enzyme.
      However, the enzyme purified from rabbit liver differs in several respects from
      known carbonyl reductases in rabbit liver.

PMID- 10963296
TI  - Anti-mouse sperm monoclonal antibody, A-1, inhibits sperm capacitation, acrosome
      reaction and calcium influx into spermatocytes.
AB  - An anti mouse sperm monoclonal antibody (A-1) inhibited sperm penetration into
      the egg zona pellucida and bound to an acrosomal area of sperm. In this study, we
      examined whether or not the antibody affects the sperm capacitation and the
      acrosome reaction. Sperm were incubated in modified Krebs-Ringer bicarbonate
      medium in the presence or absence of the antibody. The capacitation of sperm was
      assessed by chlortetracycline fluorescence pattern assay. The percentage of
      capacitated sperm did not increase in the presence of antibody, but increased
      time-dependently in its absence. The acrosome reaction of the capacitated sperm
      was induced by the addition of ionophore. The ionophore, however, failed to
      induce the reaction in the presence of the A-1 antibody. Next, the calcium influx
      into spermatocytes was examined. The capacitated sperm, preloaded with Fura-2,
      were treated with ionomycin in the presence or absence of the A-1 antibody. The
      influx of calcium ions into capacitated spermatozoa was also inhibited by the
      antibody. Thus a monoclonal antibody, A-1, inhibited the sperm capacitation,
      acrosome reaction and calcium influx into spermatocytes.

PMID- 10963297
TI  - Mithramycin represses MDR1 gene expression in vitro, modulating multidrug
      resistance.
AB  - The effect of an aureolic acid, mithramycin (MTM) on multidrug resistance (MDR)
      was investigated. At a concentration of 0.02--0.1 mg/ml (about 20--90 microM),
      MTM repressed MDR1 gene transcription of SBC-3/ADM, a MDR-phenotype subline
      derived from human small cell lung tumor. Under the same conditions, another
      aureolic acid, chromomycin A3, showed potent cytotoxicity. FACS analysis revealed
      that 5 microm MTM depleted the P-glycoprotein (Pgp) and lowered the efflux
      activity of SBC-3/ADM cells. Furthermore, MTM sensitized the cells against
      adriamycin. These results suggest that MTM would be a useful modulator of MDR
      induced by Pgp.

PMID- 10963298
TI  - Apoptosis of NG108-15 cells induced by buprenorphine hydrochloride occurs via the
      caspase-3 pathway.
AB  - Apoptosis of NG108-15 neuroblastoma x glioma hybrid cells (NG108-15 cells) is
      induced by a morphine alkaloid derivative, buprenorphine hydrochloride (Bph). In
      a previous report, we used various apoptosis inhibitors to identify the "death
      pathway," and found that caspase inhibitors Ac-YVAD-CHO (Ac-Tyr-Val-Ala-Asp-CHO)
      and Ac-DEVD-CHO (Ac-Asp-Glu-Val-Asp-CHO) did not inhibit this particular
      apoptosis. Here, we tested Z-VAD-FMK (Z-Val-Ala-Asp[OMe]-CH2F) and Z-DEVD-FMK (Z
      Asp[OMe]-Glu-[OMe]Val-Asp[OMe]-CH2F) for their ability to inhibit Bph-induced
      NG108-15 apoptosis. These tri- or tetra-peptide caspase inhibitors have a
      fluoromethyl ketone in their C-terminus instead of an aldehyde, and thus are more
      permeable than Ac-YVAD-CHO and AC-DEVD-CHO. Our observations of DNA ladder
      formation, cell morphology changes, and caspase-3 activities all indicated that
      these cell membrane-permeable caspase inhibitors completely inhibited the
      apoptosis, providing strong evidence that this apoptosis occurs through the
      caspase cascade "death pathway." Our previous report also showed that
      pretreatment of NG108-15 cells with TPCK (N-tosyl-L-phenylalanyl chloromethyl
      ketone) prevented DNA fragmentation and decreased the cell viability in Bph
      induced apoptosis. The comparison of caspase-3 activities in Bph-induced samples
      with or without TPCK pretreatment revealed that caspase-3 was activated in both
      samples. Taken together, these results indicate that the Bph-induced apoptosis of
      NG108-15 cells occurs via the conventional caspase-dependent death pathway and
      that TPCK pretreatment results in a DNA ladder-deficient apoptosis.

PMID- 10963299
TI  - Inhibition of in vitro fertilization of mouse gametes by sulfated sialic acid
      polymers.
AB  - The effect of sialic acid (N-acetyl neuraminic acid), sialic acid dimer, sialic
      acid polymers (colominic acid) and sulfated colominic acid on the activity of
      hyaluronidase, on the dispersion of cumulus cells by mouse sperm and on in vitro
      mouse fertilization (sperm penetration of zona pellucida) were evaluated. Bovine
      testicular hyaluronidase activity was significantly inhibited by colominic acid
      and sulfated colominic acid, but not by sialic acid and its dimer. The dispersion
      of cumulus cells from eggs by mouse sperm was also inhibited by colominic acid
      and sulfated colominic acid. In vitro fertilization of mouse gametes was
      inhibited by sulfated colominic acid. The IC50 value of sulfated colominic acid
      induced inhibition of fertilization was 0.3 mg/ml (ca. 0.9 mM). The value changed
      from 0.9 mM for cumulus-surrounded egg to 1.5 mM for cumulus free-egg. On the
      other hand, colominic acid showed little or no inhibitory effect on mouse in
      vitro fertilization at 0.5 mg/ml (ca. 1.6 mM). This antifertility activity by
      sulfated colominic acid did not appear to be due to an effect on sperm motility
      or on the oocytes. These results suggest that (1) the cumulus cells surrounding
      the eggs were dispersed by sperm hyaluronidase, (2) hyaluronidase was inhibited
      by colominic acid and by sulfated colominic acid, (3) sulfated colominic acid
      inhibits sperm penetration of zona pellucida by the inhibition of hyaluronidase
      and/or some enzymes required for mouse gametes fertilization.

PMID- 10963300
TI  - Expression and characterization of human rheumatoid factor single-chain Fv.
AB  - The variable region of heavy chain [V(H)] of human rheumatoid factor (hRF) IgM
      was connected with the variable region of light chain [V(L)] with the peptide
      linker (GGGSGGGSGGGS) by genetic engineering method and the single-chain Fv
      (scFv) was expressed in E. coli. On design, scFv and scFv (tag) were planned; the
      latter had a detection marker at the carboxyl-terminal. These scFvs were
      expressed as inclusion bodies in E. coli, purified in the presence of 8 M urea by
      gel filtration and renatured to the active form in vitro. As a control, the Fv,
      non-covalently associated V(H) and V(L) fragments, was also constructed. The 3
      derivatives showed almost the same binding activity to rabbit-IgG to which hRF is
      cross-reactive. ScFv (tag) was the most stable against urea among the 3
      derivatives.

PMID- 10963301
TI  - Bone-anabolic effect of salmon calcitonin on glucocorticoid-induced osteopenia in
      rats.
AB  - The anabolic effect of salmon calcitonin (SCT) on skeletal tissue was examined on
      glucocorticoid-induced osteopenia in female rats (12 weeks old). By the
      administration of methylprednisolone acetate (MPA: 0.1 mg/kg, s.c., 3 times/week)
      for 8 weeks, histomorphometrically detectable osteopenia with the characteristics
      of decreased bone formation and increased bone resorption developed in proximal
      tibia metaphysis. Serum osteocalcin level was also decreased by MPA treatment.
      Subsequent treatment with SCT (10 U/kg, s.c., 5 times/week) was found to reverse
      once developed osteopenia with the return of the osteocalcin level, though rats
      were still on MPA. Histomorphometry revealed that SCT decelerated bone resorption
      but augmented bone formation in this osteopenic model. After a single injection
      of SCT (2.5 U/kg--40 U/kg, s.c.), the serum level of parathyroid hormone (PTH)
      which had a potent anabolic on bone formation increased in a dose-dependent
      manner. These results indicate that SCT has a stimulating effect on osteoblastic
      bone formation and this anabolic effect may at least in part be due to its
      indirect effect to increase endogenous PTH secretion.

PMID- 10963302
TI  - Comparison of the antidiarrheal effects of wood creosote and loperamide in the
      rat jejunum and colon in vitro.
AB  - Wood creosote, a mixture of guaiacol, creosol and related compounds, has long
      been used as an antidiarrheal agent. The goal of our study was to investigate the
      antisecretory effect of wood creosote and to compare it to the effect of
      loperamide, a synthetic opioid widely used in the treatment of diarrhea.
      Experiments were performed in rat jejunal and colonic mucosal sheets, mounted in
      modified Ussing chambers. Active electrogenic transport was monitored
      electrically as short circuit current (Isc) and hypersecretory responses were
      induced by acetylcholine (ACh). Neither loperamide nor wood creosote had any
      significant effect on basal lsc, when added to the serosal bathing solution at
      concentrations of 0.1-50microg/ml. In contrast, under hypersecretory conditions,
      both agents showed concentration-dependent (0.1--100microg/ml) antisecretory
      effects inhibiting ACh-induced responses in the jejunum and colon. However, the
      effects suggest regional differences, with loperamide being most potent in the
      jejunum, while wood creosote showed equal potency in both jejunum and colon.
      Based upon these in vitro findings, we conclude that like loperamide, the
      antidiarrheal action of wood creosote is due, at least in part, to its
      antisecretory activity.

PMID- 10963304
TI  - Differentiation-inducing activity of lupeol, a lupane-type triterpene from
      Chinese dandelion root (Hokouei-kon), on a mouse melanoma cell line.
AB  - We examined the differentiation-inducing effects of extracts of 49 wild plants,
      25 types of seaweed and 26 mushrooms in Akita on the human leukemia cell line
      HL60 and a B16 mouse melanoma-derived sub-clone with high differentiation
      capability (B16 2F2). Differentiation inducers of HL60 cells such as retinoic
      acid, showed no effects on the differentiation of B16 2F2 cells. Furthermore,
      chemical compounds known to be inducers of B16 cells, did not induce
      differentiation of HL60 cells. Screening tests showed that the differentiation of
      HL60 cells was induced by extracts of 28 wild plants, 10 types of seaweed and 2
      mushrooms, and melanogenesis of B16 2F2 cells was increased by extracts of 21
      wild plants, 8 types of seaweed and 7 mushrooms. All of the alcoholic extracts of
      plants belonging to the subfamily Cichorioideae of the family Compositae caused
      cell differentiation of the melanoma cell line. The extracts of Chinese dandelion
      root, also inhibited cell growth and induced melanogenesis of B16 2F2 cells. We
      isolated the active compound from ethanol extracts of the crude drug. Chemical
      and physical data for the active compound were identical with those for lupeol, a
      lupane-type triterpene.

PMID- 10963303
TI  - Local thrombus formation in the site of intravenous injection of chlorpromazine:
      possible colloid-osmotic lysis of the local endothelial cells.
AB  - Since amphiphilic drugs are known to interact with biomembranes, we investigated
      local vessel damage and thrombosis which might be brought about by intravenous
      dosing using chlorpromazine (CPZ) as a representative compound. CPZ-induced
      hemolysis was suppressed by an increase in sucrose concentration in the medium,
      characterizing this hemolysis to be colloid-osmotic lysis, which includes the
      enhancement of membrane phospholipid fluidity and consequent small pore formation
      in the membranes. This was supported by the observation that hemolysis by
      filipin, not featuring the stage of small pore formation, was not affected by
      sucrose. [14C]Glucose-entrapping liposomes were degraded by CPZ, and this
      degradation was enhanced by an increase in the intravesicle glucose
      concentration. These results indicated that the compound could induce colloid
      osmotic lysis in erythrocytes and artificial membrane vesicles. CPZ also injured
      cultured porcine aortic endothelial cells (PAEC), as evidenced by lactate
      dehydrogenase (LDH) leakage. This injury was also suppressed by increase in
      sucrose concentration in the medium, suggesting that colloid-osmotic lysis again
      occurred. When rats were intravenously injected with CPZ, local endothelial cell
      (EC) injury and associated thrombus formation were observed, suggesting that
      CPZ's action was also evident in vivo. To our knowledge, this is the first
      finding which suggests that an intravenously dosed amphiphilic drug can injure
      local ECs based on a colloid-osmotic lysis mechanism leading to thrombosis.

PMID- 10963306
TI  - Effect of intranasal administration of Lactobacillus fermentum on the respiratory
      tract of mice.
AB  - This paper studied the effect of intranasal inoculation of Lactobacillus
      fermentum, a microorganism belonging to the normal flora of the mouse pharynx, on
      the respiratory tract of mice. Optimal temporary colonization in different areas
      of the tract was obtained through administration of 4 times a dose of 5 x 10(7)
      CFU. L. fermentum remained in the trachea and bronchi up to the 7th day after
      inoculation. Re-inoculation of lactobacilli on the 10th day produced a transient
      colonization of the respiratory tract. Histological modifications produced in the
      trachea were mainly observed as an increased lymphocyte population at sub-mucosa
      level on the 4th day after inoculation. There was an increased number of
      activated macrophages in cytological slides of lung tissues on days 2 and 4. Re
      inoculation also produced stimulation of the G2 macrophages on days 12, 14 and
      17. From a histological point of view there were no other important changes in
      the organs studied. These results suggest stimulation of the immune system,
      especially that of the mucosal surfaces, after intranasal administration of L.
      fermentum in the experimental model employed. Stimulation was reflected in
      tracheal lymphocyte proliferation and increased lung macrophage population which
      have to be further studied in more detail.

PMID- 10963305
TI  - Bioavailability of ciprofloxacin and fleroxacin: results of a preliminary
      investigation in healthy adult Nigerian male volunteers.
AB  - The absolute bioavailability (BA) of ciprofloxacin and fleroxacin were evaluated
      in 19 adult Nigerian male volunteers. Subjects meeting the selection criteria
      were randomized to receive treatment either with fleroxacin (200 mg-i.v. and 200
      mg oral dose) or ciprofloxacin (200 mg-i.v. and 250 mg oral dose). The i.v./oral
      or oral/i.v. switch was made after a one week washout period. Blood and urine
      samples were collected at pre-determined time intervals over a 72 h period for
      analysis of drug levels. Following intravenous administration the maximum serum
      concentration (Cmax) was 2.7+/-1.06mg/l for ciprofioxacin and 0.99+/-0.41 mg/l
      for fleroxacin; the area under the blood level curve (AUC) was 8.82+/-3.19 mg x
      h/l with ciprofloxacin and 8.52+/-3.83 mg x h/l with fleroxacin. Following oral
      administration the Cmax was 1.52+/-0.94 mg/l with ciprofloxacin and 0.57+/-0.08
      mg/l with fleroxacin; the AUC was 9.87+/-4.10 and 7.55+/-1.42 mg x h/l,
      respectively. The absolute BA following oral administration was found to be
      0.79+/-0.47 for ciprofloxacin and 1.01+/-0.78 for fleroxacin. When these BA
      results were corrected for renal clearance [Cl(r)] and elimination half-life
      (t1/2) the values were reduced to 0.37+/-0.17 and 0.31+/-0.18, respectively, for
      ciprofloxacin and 0.53+/-0.23 and 0.99+/-0.38, respectively, for fleroxacin. Only
      38% with ciprofloxacin and 59% with fieroxacin, of the administered dose, was
      excreted unchanged following oral administration. More work, however, needs to be
      done on ciprofloxacin to support and/or confirm the above findings. Fleroxacin,
      on the one hand, exhibited a different trend from that observed in the literature
      with respect to Cmax and AUC where the values observed in this study were 3--4
      fold lower than expected following identical doses, whilst on the other hand the
      observed BA profile in this study was consistent with literature trends.

PMID- 10963307
TI  - Roles of hydrophobicity, protein binding and the probenecid-sensitive transport
      system in the cerebrospinal fluid delivery of nucleoside analogues with anti
      viral activity.
AB  - Ten nucleoside analogues with anti-herpes or anti-HIV activity were investigated
      for their transport into the cerebrospinal fluid (CSF) following intravenous
      administration in rats. The novel anti-herpes agent 1-beta-D-arabinofuranosyl-2
      thio-5-fluorocytosine (5F-araSC) showed the highest CSF/plasma concentration
      ratio (>20%), while that of acyclovir (ACV) was very low (<5%). A linear
      relationship was observed between the partition coefficient (chloroform/water)
      and CSF/unbound plasma concentration in 6 of 9 agents. The exceptions were DDI,
      AZT and ACV, which showed much lower concentrations in the CSF than expected from
      their hydrophobicity and protein binding activities. The effects of probenecid
      treatment on the CSF and plasma concentrations were measured with continuous
      intravenous administration of ACV, AZT, araC and 5F-araSC. Probenecid markedly
      increased the CSF concentrations of ACV and AZT, although the effect was minimal
      in araC and 5F-araSC. These results may provide useful information for molecular
      design of nucleoside analogues with better transport to the brain.

PMID- 10963308
TI  - [1-11C]Octanoate as a PET tracer for studying ischemic stroke: evaluation in a
      canine model of thromboembolic stroke with positron emission tomography.
AB  - Octanoate is taken up by the brain and converted in astrocytes to glutamine
      through the TCA cycle after beta-oxidation. Consequently, [1-11C]octanoate might
      serve as a useful positron emission tomography (PET) probe for studying cerebral
      oxidative metabolism and/or astroglial functions. The present study attempted to
      evaluate the utility of using [1-11C]octanoate as a PET tracer for imaging and
      evaluating the pathophysiology of ischemic stroke. We used a canine model of
      thromboembolic stroke. Five male beagle dogs were implanted with an indwelling
      catheter in the left internal carotid artery. A single autologous blood clot was
      injected into the left internal carotid artery through the catheter. The brain
      distribution of [1-11C]octanoate and cerebral blood flow (CBF) were determined 24
      h after insult using a high resolution PET scanner. Post mortem brain regions
      unstained with 2,3,5-triphenyltetrazolium chloride (TTC) were defined as
      infarcts. In the region of an infarct, accumulation of [1-11C]octanoate decreased
      concurrently with CBF reduction. In contrast, normal accumulation of [1
      11C]octanoate was observed in ischemic but vital regions, suggesting that an
      increased accumulation of [1-11C]octanoate relative to CBF takes place in these
      regions. In conclusion, [1-11C]octanoate accumulated in ischemic but vital
      regions, indicating that [1-11C]octanoate is a potentially useful PET tracer for
      imaging and evaluating the pathophysiology of ischemic stroke.

PMID- 10963310
TI  - Antifungal activity of Hinokitiol-related compounds on wood-rotting fungi and
      their insecticidal activities.
AB  - Hinokitiol (beta-thujaplicin), beta-dolabrin and gamma-thujaplicin isolated from
      Thujopsis dolabrata SIEB. et ZUCC var hondai MAKINO showed antifungal activities
      against all of the wood-rotting fungi examined. The antifungal activity of three
      compounds on Daedalea dickinsii IFO-4979 was especially strong, their minimum
      inhibitory concentration (MIC) values being 0.2 microg/ml. Their antifungal
      activities on D. dickinsii IFO-4979 were as high as that of amphotericin B used
      as a positive control. Three compounds had strong insecticidal activities on
      Tyrophagus putrescentiae [50%-lethal concentration (LC50 : g/m2) 0.25 in
      hinokitiol, 0.02 in beta-dolabrin and gamma-thujaplicin. Their insecticidal
      activities were higher than that of N,N-diethyl-m-toluamide (DEET, LC50 : 1.46
      g/m2) used as a positive control. Three compounds also showed strong insecticidal
      activity on Coptotermes formosanus [LC50 (g/m2) 0.07 in hinokitiol, 0.05 in beta
      dolabrin and gamma-thujaplicin], although their insecticidal activities were much
      lower than that of commercial chloropyrifos (LC50 : 0.00016 g/m2).

PMID- 10963309
TI  - Antioxidant properties of a new type of polyene, falconensone A and its
      derivatives.
AB  - Falconensones A and B are new type of yellow compound extracted from ascomycetous
      fungi, Emericella falconensis. Falconensone A p-bromophenylhydrazone and
      falconensone A dioxime are derivatives of falconensone A which have also been
      synthesized recently. The structural similarity of the falconensones to alpha
      tocopherol (vitamin E) led us to investigate whether falconensones exhibit
      antioxidant activity. These studies found that falconensone A p
      bromophenylhydrazone and falconensone A dioxime scavenge alpha,alpha-diphenyl
      beta-picrylhydrazyl (DPPH) radical in a 1 : 1 ratio in contrast to vitamin E,
      where a 1 : 2 ratio relative to DPPH radicals was observed. In addition, linoleic
      acid peroxidation initiated by hydroxyl radicals was diminished by falconensone A
      p-bromophenylhydrazone to a greater extent than by vitamin E, and lipid
      peroxidation in rat liver microsome was reduced by falconensone A dioxime and
      falconensone A p-bromophenylhydrazone. In contrast, falconensone A and
      falconensone B, the 4'-nor-methyl derivative of falconensone A, showed much lower
      activity or were inactive in scavenging radicals. These results suggest that
      falconensone A p-bromophenylhydrazone and falconensone A dioxime, may be useful
      new antioxidant agents, wherein the bromophenyl and hydroxy residues of
      falconensone A may be important for antioxidant activity. Based on these results,
      derivatives of falconensone A appear to be effective antioxidants that may have
      clinical utility for diseases treated with vitamin E.

PMID- 10963311
TI  - The involvement of two specific arginine residues in the action of HM-1 killer
      toxin was deduced from site-directed mutagenesis.
AB  - Each of the four arginine residues in the HM-1 killer toxin was replaced by
      alanine using site-directed mutagenesis. The polymerase chain reaction (PCR)
      constructed mutant gene was successfully expressed in HM-1 toxin resistant
      Saccharomyces cerevisiae. Among four HM-1 toxin analogues, R82A HM-1 toxin and
      R86A HM-1 toxin lost killer activity, while R61A HM-1 toxin and R85A HM-1 toxin
      retained activity. These results strongly indicate the importance of the arginine
      residues at positions 82 and 86 which are located in the C-terminal region of the
      HM-1 toxin for the action of killer activity.

PMID- 10963312
TI  - Variation in the frequency of micronucleated hepatocytes following time course
      treatment in the mouse: liver micronucleus assay of partially hepatectomized
      tissues.
AB  - The time-course pattern of the frequency of micronucleated hepatocytes in vivo
      after partial hepatectomy (PH) was studied in mice using N-nitrosodimethylamine
      (DMN), N-nitrosodiethylamine (DEN), and 1,2-dimethylhydrazine (DMH), which are
      rodent liver carcinogens with potent clastogenic activity in the liver. With all
      chemicals, production of micronucleated hepatocytes was not clearly observed at 3
      d after PH, but was clear 4 or 5 d after PH. We propose that it is preferable to
      perform a preliminary assay prior to the main assay when estimating the
      clastogenic potential of certain chemicals towards hepatocytes in vivo.

PMID- 10963314
TI  - Correlation between neurotoxic events and intracerebral concentration of
      tacrolimus in rats.
AB  - The neurotoxicity associated with tacrolimus is one of the major limitations for
      its administration after organ transplantation. This study investigated the
      correlation between neurotoxicity and the intracerebral concentration of
      tacrolimus. Rats were given one of three doses of tacrolimus (5, 10, and 20
      mg/kg/d) orally twice a day for 2 weeks and neurotoxic events were observed. The
      rats were sacrificed on either day 7 or 14. The trough values of the whole blood
      and the corresponding intracerebral concentrations were then measured. None of
      the rats receiving dosage of 5 mg/kg/d showed any neurotoxic symptoms throughout
      the two-week test period. In rats receiving a dosage of 10 mg/kg/d, however, all
      seven surviving rats presented tremors or seizures during the second week. In
      rats receiving a dosage of 20 mg/kg/d, 40% of the rats presented tremors or
      seizures during the first week. The threshold concentration of tacrolimus in the
      brain resulting in neurotoxic events was therefore estimated as approximately 700
      ng/g. At concentrations over this threshold value, the intensity of the
      neurological event increases with the concentrations of tacrolimus in the brain.
      Using a linear correlation between the whole blood and intracerebral
      concentrations (r=0.967) of tacrolimus, the pharmacological threshold for the
      whole blood trough level was estimated as approximately 20 ng/ml, which falls
      into the same value reported for the incidental threshold of neurotoxicity in
      renal transplant recipients [Bottiger et al., Br. J. Clin. Pharmacol., 48, 445-
      448 (1999)]. Therefore, it is suggested that the rat is a good animal model to
      quantitatively evaluate the risk of neurotoxicity associated with tacrolimus in
      human, and that frequent measurement of whole blood tacrolimus concentrations is
      important for predicting and preventing neurotoxic events.

PMID- 10963313
TI  - Differentiation-inducing effect of magnolialide, a 1 beta-hydroxyeudesmanolide
      isolated from Cichorium intybus, on human leukemia cells.
AB  - Cichorium intybus contains two 1beta-hydroxyeudesmanolides, magnolialide and
      artesin, together with several constituents. Magnolialide inhibits the growth of
      several tumor cell lines and appears to induce differentiation of human leukemia
      HL-60 and U-937 cells to monocyte/macrophage-like cells. Another 1beta
      hydroxyeudesmanolide, artesin, and other constituents were inactive. The content
      of magnolialide was shown to be highest in the leaves of Inje cultivar among the
      cultivars investigated in this study.

PMID- 10963315
TI  - Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester
      oligonucleotide encapsulated into fusogenic liposomes.
AB  - We report here the antisense effect of phosphodiester oligodeoxynucleotide (D
      ODN) using fusogenic liposomes (FL) as its carrier. FL has envelope proteins of
      the Sendai virus within its membrane and introduces its contents directly and
      efficiently into cytosol by means of the virus-cell fusion mechanism. Using
      antisense (AS) D-ODN 15-mer complementary to the c-myc proto-oncogene mRNA,
      including the translation initiation codon site, we analyzed the growth of HL-60
      cells by [3H]-thymidine uptake. AS-ODNs encapsulated in FL inhibited the growth
      by about 70% that of the control HL-60 cells at 2.48 microM. In contrast, sense
      and scramble D-ODNs encapsulated in FL showed no effect of the growth of HL-60
      cells at the same concentration. Even at 50 microM, free form D-ODNs did not show
      any effect. These results suggest that FL is potentially a useful delivery
      vehicle for oligonucleotide-based therapeutics, and that D-ODN may be a likely
      candidate for oligodeoxynucleotides when an efficient delivery system is used.

PMID- 10963316
TI  - Medical trainee experience versus optimizing clinical outcomes: achieving the
      best of both.

PMID- 10963317
TI  - The utilization of long-term home oxygen therapy in the United States: a few
      observations and some suggestions.

PMID- 10963318
TI  - The impact of a respiratory therapy consult service on house officers' knowledge
      of respiratory care ordering.
AB  - BACKGROUND: Although available studies show that implementation of respiratory
      care protocols by respiratory therapists can enhance the allocation of
      respiratory care services, concern has been expressed that respiratory
      therapists' involvement in assessing patients and in determining treatment plans
      may detract from medical trainees' education and experience in ordering
      respiratory care services. OBJECTIVE: Compare the rates of correct responses to
      case-based questions about respiratory care ordering in two groups of internal
      medicine house officers at academic medical centers: one group training at an
      institution using respiratory care protocols (The Cleveland Clinic Foundation)
      and the other group training in an institution at which respiratory care
      protocols have not been used (University of Nebraska). DESIGN: Prospective cohort
      study. SETTING: Two academic medical centers, one using respiratory protocols and
      the other not using respiratory care protocols. MEASUREMENTS: Percent of correct
      responses to questions regarding respiratory care management posed in 5 case
      studies administered to both groups. RESULTS: Responses were available from 41
      and 17 internal medicine house officers at The Cleveland Clinic Foundation and
      University of Nebraska, respectively. Respondents represented postgraduate years
      one, two, and three, and constituted a similar percentage of all internal
      medicine house officers at each institution (33%). The rate of correct responses
      to the 20 questions posed in the 5 case studies was high overall (76.8%) and
      similar in the two house staff groups (77.2 +/- 11.6% at The Cleveland Clinic
      Foundation and 75.8 +/- 12.0% at University of Nebraska, p = 0.69). The 95%
      confidence interval for the difference straddled zero (-5.4%, 8.1%), making it
      very unlikely that any important difference exists between the two groups in rate
      of correct responses. Analysis of covariance also showed no difference between
      groups, suggesting that postgraduate training level did not affect this
      conclusion. In one of the 5 case studies, the percent of correct responses was
      higher among trainees where respiratory care protocols were in use (86.8 +/- 18%
      at The Cleveland Clinic Foundation vs 69.1 +/- 14% at University of Nebraska, p =
      0.0001). CONCLUSIONS: In this comparison of internal medicine house officers'
      knowledge regarding respiratory care ordering at institutions using versus not
      using respiratory care protocols, the rates of correct responses by both groups
      were similar and unlikely to differ significantly. For one of the 5 case studies,
      respondents from the institution using respiratory care protocols scored
      significantly higher. Taken together, these results suggest that use of
      respiratory care protocols implemented by respiratory therapists does not detract
      from internal medicine trainees' expertise in respiratory care management.
      Whether these results generalize to other institutions or reflect expertise in
      actual practice remains uncertain.

PMID- 10963320
TI  - Recommendations of the Fifth Oxygen Consensus Conference. Writing and Organizing
      Committees.
AB  - It should be recognized that the advent of LTOT created a new health care system
      that is based on powerful scientific data. Oxygen therapy studies such as those
      by the Nocturnal Oxygen Therapy Trial Group and the British Medical Research
      Council study clearly demonstrated that LTOT improves both the length and quality
      of life of hypoxemic COPD patients. Keeping patients at home and out of the
      hospital or nursing home has both psychosocial and economic benefits. Efforts
      should be towards enhancing, not limiting., the availability of LTOT.

PMID- 10963321
TI  - Introduction of a single isomer beta agonist.
AB  - The release of levalbuterol offers the first approved single-isomer beta agonist
      for oral inhalation. Data from in vitro studies support the concept that S
      albuterol is not inactive and may have properties antagonistic to
      bronchodilation. There is some variability in the results of clinical studies
      with the separate isomers of albuterol, which suggests the need for further
      study. The introduction of levalbuterol into general clinical use in managing
      asthma and chronic obstructive disease should begin to offer additional
      information on the effects of a single isomer beta agonist in comparison to
      previous racemic mixtures.

PMID- 10963319
TI  - Benzocaine-associated methemoglobinemia following bronchoscopy in a healthy
      research participant.
AB  - Benzocaine (ethyl aminobenzoate) is a local anesthetic commonly used to achieve
      topical anesthesia of the skin and mucous membranes prior to endoscopic
      procedures. Methemoglobinemia, a condition in which hemoglobin cannot bind and
      deliver oxygen normally, has been associated with benzocaine use in various
      patient populations. This is the first report of benzocaine-associated
      methemoglobinemia occurring in a healthy research participant. The research
      participant developed a methemoglobin level of 27% and marked cyanosis. No
      adverse sequelae other than cyanosis were identified. This report extends the
      population in which benzocaine-associated methemoglobinemia has been described.
      Additionally, this report supports the observation that methemoglobin levels
      approaching 30% may be tolerated in otherwise healthy individuals, producing few
      clinically important effects. Finally, this case also indicates that, in
      obtaining informed consent for a procedure in which benzocaine will be
      administered, patients and research participants should be specifically informed
      of the risk of benzocaine-induced methemoglobinemia. This information is
      especially important in those settings in which the manufacturer-recommended dose
      of benzocaine may either intentionally or inadvertently be exceeded.

PMID- 10963322
TI  - Pulmonary function in obesity.

PMID- 10963323
TI  - Peak expiratory flow vs spirometry in a patient with asthma.

PMID- 10963324
TI  - Testing conditions for nebulizers.

PMID- 10963325
TI  - Is the Health Care Financing Administration the standard of care for the oxygen
      dependent patient?

PMID- 10963326
TI  - Genetically modified foods: a case of information or misinformation?

PMID- 10963327
TI  - Oxidative stress in bacteria and protein damage by reactive oxygen species.
AB  - The advent of O2 in the atmosphere was among the first major pollution events
      occurred on earth. The reaction between ferrous iron, very abundant in the
      reductive early atmosphere, and oxygen results in the formation of harmful
      superoxide and hydroxyl radicals, which affect all macromolecules (DNA, lipids
      and proteins). Living organisms have to build up mechanisms to protect themselves
      against oxidative stress, with enzymes such as catalase and superoxide dismutase,
      small proteins like thioredoxin and glutaredoxin, and molecules such as
      glutathione. Bacterial genetic responses to oxidative stress are controlled by
      two major transcriptional regulators (OxyR and SoxRS). This paper reviews major
      key points in the generation of reactive oxygen species in bacteria, defense
      mechanisms and genetic responses to oxidative stress. Special attention is paid
      to the oxidative damage to proteins.

PMID- 10963328
TI  - Molecular phylogeny: pitfalls and progress.
AB  - Molecular phylogeny based on nucleotide or amino acid sequence comparison has
      become a widespread tool for general taxonomy and evolutionary analyses. It seems
      the only means to establish a natural classification of microorganisms, since
      their phenotypic traits are not always consistent with genealogy. After an
      optimistic period during which comprehensive microbial evolutionary pictures
      appeared, the discovery of several pitfalls affecting molecular phylogenetic
      reconstruction challenged the general validity of this approach. In addition to
      biological factors, such as horizontal gene transfer, some methodological
      problems may produce misleading phylogenies. They are essentially (i) loss of
      phylogenetic signal by the accumulation of overlapping mutations, (ii)
      incongruity between the real evolutionary process and the assumed models of
      sequence evolution, and (iii) differences of evolutionary rates among species or
      among positions within a sequence. Here, we discuss these problems and some
      strategies proposed to overcome their effects.

PMID- 10963329
TI  - Biosorption: a solution to pollution?
AB  - To solve the water pollution problem by toxic heavy metal contamination resulting
      from humans technological activities has for long presented a challenge.
      Biosorption can be a part of the solution. Some types of biosorbents such as
      seaweeds, molds, yeasts, bacteria or crab shells are examples of biomass tested
      for metal biosorption with very encouraging results. The uptake of heavy metals
      by biomass can in some cases reach up to 50% of the biomass dry weight. New
      biosorbents can be manipulated for better efficiency and multiple re-use to
      increase their economic attractiveness.

PMID- 10963330
TI  - Microbiology of the stalactites from Grotta dei Cervi, Porto Badisco, Italy.
AB  - The active stalactites from Grotta dei Cervi, Porto Badisco, southeastern Italy,
      were sampled to investigate the microbial communities present in these
      speleothems. Sampling was carried out in a transect about 150 m long in the
      central gallery, where numerous Gram-positive bacteria were isolated.
      Actinomycetes of the genus Streptomyces were the most abundant, followed by
      members of the genus Bacillus. Further isolates were assigned to the genera
      Amycolatopsis, Arthrobacter; Agromyces. Micrococcus, Nocardiopsis and Rhodococcus
      of the order Actinomycetales. The ability of actinomycetes to colonize
      subterranean environments is discussed.

PMID- 10963331
TI  - Rapid identification of Salmonella typhimurium, S. enteritidis and S. virchow
      isolates by polymerase chain reaction based fingerprinting methods.
AB  - In this study we used and evaluated three rapid molecular typing methods for the
      identification of three frequent, clinically significant Salmonella serovars on
      the basis of the ease, simplicity and reproducibility of the chosen methods. We
      determined the genetic diversity among several isolates of Salmonella
      enteritidis, S. typhimiurium and S. virchow, and compared them with other
      enterobacteria by using the repetitive extragenic palindromic (REP) sequences,
      the enterobacterial repetitive intergenic consensus (ERIC) sequences, and the 16S
      23S rDNA intergenic spacer region (ITS 1). The objective was to evaluate their
      potential application to discriminate among members of the species Salmonella
      enterica subspecies enterica using the genetic diversity of the group found by
      genomic fingerprinting. The three different serovars of Salmonella studied gave
      reproducible and distinguishable profiles using whichever of the above mentioned
      polymerase chain reaction (PCR) methods assayed. The conserved patterns in each
      serovar allowed for easy differentiation from other serovars of Salmonella.

PMID- 10963332
TI  - Rapid extracellular acidification induced by glucose metabolism in non
      proliferating cells of Serratia marcescens.
AB  - The addition of glucose or other sugars to resting cells of Serratia maurcescens
      induced rapid acidification of the extracellular medium. This acidification was
      due to the catabolism of sugars. The rate of acidification depended on the carbon
      source and its concentration. HPLC analysis of the supernatants demonstrated that
      the progressive fall in pH resulted from the rapid production of lactic, acetic,
      pyruvic and citric acids. Other microorganisms were tested for their ability to
      produce this rapid acidification of the medium. This study may provide a rapid
      and simple method for metabolism studies.

PMID- 10963333
TI  - DNA fluorescent stain accumulates in the Golgi but not in the kinetosomes of
      amitochondriate protists.
AB  - Hindgut symbiotic trichomonads (uninucleate Caduceia versatilis, and
      multinucleate Stephanonympha sp. and Snyderella tabogae) from the dry-wood-eating
      termite Cryptotermes cavifrons (Kalotermitidae) accumulate DAPI (4,6diamidino-2
      phenylindole) in the membranous sacs of the Golgi complex. This form of Golgi
      complex, typical of protists in the class Parabasalia, is called a parabasal
      body. Trichomonads contain organellar systems, mastigonts, that consist of four
      undulipodia (e.g. eukaryotic flagella and cilia), axostylar microtubules, a
      parabasal body and other structures. These cells bear from one (in the case of
      Caduceia) to hundreds (in the case of Snyderella) of mastigonts. These features
      are characteristic of their protist class (Parabasalia). The nuclei of all three
      species stained with DNA-specific stains: DAPI, SYTOX, acridine orange, propidium
      iodide, ethidium bromide and Feulgen, at optimal concentrations, but kinetosomes
      failed to stain at all. The nuclei, parabasal bodies and symbiotic bacteria (but
      no microtubular structures) fluoresced in glutaraldehyde-fixed cells stained with
      1.45 microM DAPI. Parabasal bodies of Snyderella and Caduceia treated to remove
      lipids with Triton X-100, or treated with 5% trichloroacetic acid, lacked DAPI
      fluorescence. I conclude that DNA, present as expected in nuclei and bacterial
      symbionts, is absent from and not associated with calonymphid kinetosomes. The
      reason for DNA-RNA stain accumulation in the Golgi cistemae is not clear.

PMID- 10963334
TI  - Identification of Vibrio spp. (other than V. vulnificus) recovered on CPC agar
      from marine natural samples.
AB  - Two hundred and eighty four presumptive but not confirmed Vibrio vulnificus
      isolates grown on cellobiose-polymixin B-colistin agar (CPC) at 40 degrees C,
      recovered from sea water samples from Valencia, Spain, during a microbiological
      survey for V. vulnificus, were phenotypically identified. Most of the isolates
      (91%) corresponded to Vibrio species. V. harveyi (24%) and V. splendidus(19%)
      were the most abundant species identified, followed by V. navarrensis (13%), V.
      alginolyticus (8%) and V. parahaemolyticus (5%). The ability to grow on CPC agar
      and ferment cellobiose of several V. vulnificus strains from different origins
      and serovars, including reference strains, was tested. Most serovar E isolates
      and 25% of non-serovar E isolates could not grow on CPC agar.

PMID- 10963335
TI  - The wonderful lives of Joseph Leidy (1823-1891).

PMID- 10963336
TI  - Ramon y Cajal, microbiologist.

PMID- 10963337
TI  - Immunological hiding of herpesvirus-infected cells.
AB  - Over the past years, numerous research groups have discovered various strategies
      that herpesviruses use to hide themselves from recognition by the immune system
      of their hosts. The current review gives a summary of this research, with
      emphasis on the mechanisms by which herpesvirus-infected cells escape from
      elimination by complement, phagocytes, cytotoxic T-lymphocytes and/or natural
      killer cells.

PMID- 10963338
TI  - Ineffective control of murine cytomegalovirus by IE1-specific cytotoxic T
      lymphocytes during protracted infection in the lung.
AB  - Interstitial pneumonia caused by cytomegalovirus (CMV) is a fatal disease in
      immunocompromised patients. In order to examine the defense mechanism against the
      virus in the lung, we employed an intratracheal infection model in susceptible
      mice. In mice infected intratracheally with murine CMV, a protracted infection
      was observed where infectious virus was detected up to 21 days of infection.
      During this prolonged infection, massive accumulation in the lung of CD8+ T cells
      with activated phenotypes occurred and these CD8+ T cells showed direct ex vivo
      cytolytic activity against target cells pulsed with the nonamer peptide derived
      from IE1 protein of the virus, which has been shown to be the dominant epitope
      recognized by most of virus-specific CTL. Moreover, adoptive transfer of in vitro
      induced IE1 peptide-specific CTL line showed no anti-virus effect in the lung,
      although they were effective in the spleen. Hence, there is reason to assume the
      IE1-specific CTL induced in vivo or in vitro plays limited roles during the
      prolonged infection in the lung.

PMID- 10963339
TI  - Expression of stable hepatitis B viral polymerase associated with GRP94 in E.
      coli.
AB  - We here presented evidence that a 94-kDa glucose-regulated protein (GRP94) was
      associated with hepatitis B viral (HBV) polymerase in the human liver cell HepG2
      and this association could be applied even in Escherichia coli. We investigated
      the role of GRP94 in the expression and stabilization of HBV polymerase in
      Escherichia coli by coexpression of the two proteins. The affinity column
      purified glutathione S-transferase-tagged HBV polymerase (GST-P, 130 kDa) showed
      a proper molecular size and reverse transcriptase activity on several exogenous
      templates and was sensitive to specific inhibitors. The GST-P was associated with
      the maltose-binding protein-tagged GRP94 (MBP-GRP94, 130 kDa) using analyses by
      an affinity chromatography, native gel electrophoresis and glycerol gradient
      centrifugation. However, nondenaturing and partially denaturing activity gel
      analyses showed two active bands of approximately 260 kDa and approximately 130
      kDa, respectively. Furthermore, in the presence of the encapsidation signal RNA
      template (HBV epsilon RNA), the approximately 260-kDa active band was gradually
      converted to approximately 130 kDa, which implies that HBV polymerase was
      dissociated from the chaperone GRP94 and bound preferentially to the HBV epsilon
      RNA. These results suggested that the chaperone GRP94 was necessary for the
      stabilization and production of HBV polymerase as an active form.

PMID- 10963340
TI  - Expression of the hepatitis E virus ORF1.
AB  - Hepatitis E virus (HEV) is an unclassified, plus-strand RNA virus whose genome
      contains three open reading frames (ORFs). ORF1, the 5' proximal ORF of HEV,
      encodes nonstructural proteins involved in RNA replication which share homology
      with the products of the corresponding ORF of members of the alphavirus-like
      superfamily of plus-strand RNA viruses. Among animal virus members of this
      superfamily (the alphavirus and rubivirus genera of the family Togaviridae), the
      product of this ORF is a nonstructural polyprotein (NSP) that is cleaved by a
      papain-like cysteine protease (PCP) within the NSP. To determine if the NSP of
      HEV is similarly processed, ORF1 was introduced into a plasmid vector which
      allowed for expression both in vitro using a coupled transcription/translation
      system and in vivo using a vaccinia virus-driven transient expression system. A
      recombinant vaccinia virus expressing ORF1 was also constructed. Both in vitro
      and in vivo expression under standard conditions yielded only the full-length 185
      kDa polyprotein. Addition of co-factors in vitro, such as divalent cations and
      microsomes which have been shown to activate other viral proteases, failed to
      change this expression pattern. However, in vivo following extended incubations
      (24-36 hours), two potential processing products of 107 kDa and 78 kDa were
      observed. N- and C-terminus-specific immunoprecipitation and deletion mutagenesis
      were used to determine that the order of these products within the NSP is NH2-78
      kDa-107 kDa-COOH. However, site-specific mutagenesis of Cys483, predicted by
      computer alignment to be one member of the catalytic dyad of a PCP within the
      NSP, failed to abolish this cleavage. Additionally, sequence alignment across HEV
      strains revealed that the other member of the proposed catalytic dyad of this
      PCP, His590, was not conserved. Thus, the cleavage of the NSP observed following
      prolonged in vivo expression was not mediated by this protease and it is doubtful
      that a functional PCP exists within the NSP. Attempts to detect NSP expression
      and processing in HEV-infected primary monkey hepatocytes were not successful and
      therefore this proteolytic cleavage could not be authenticated. Overall, the
      results of this study indicate that either the HEV NSP is not processed or that
      it is cleaved at one site by a virally-encoded protease novel among alpha-like
      superfamily viruses or a cellular protease.

PMID- 10963341
TI  - Characterization of human symptomatic rotavirus isolates MP409 and MP480 having
      'long' RNA electropherotype and subgroup I specificity, highly related to the
      P6[1],G8 type bovine rotavirus A5, from Mysore, India.
AB  - In an epidemiological study of symptomatic human rotaviruses in Mysore, India
      during 1993 and 1994, isolates MP409 and MP480 were isolated from two children
      suffering from severe, acute dehydrating diarrhea. Both isolates exhibited 'long'
      RNA pattern and subgroup I specificity suggesting the likelihood of their animal
      origin. Both isolates did not react with monoclonal antibodies (MAbs) specific
      for serotypes G1 to G6 as well as G10. To determine the genetic origin of these
      isolates, complete nucleotide sequences of genes encoding the outer capsid
      proteins VP4 and VP7, nonstructural proteins NSP1 and NSP3 and viral enterotoxin
      protein NSP4 from MP409 and partial sequences of genes from MP480 were
      determined. Comparison of the 5' and 3' terminal sequences of 250 nucleotides
      revealed complete identity of the gene sequences in both strains suggesting that
      MP409 and MP480 are two different isolates of a single strain. Comparison of the
      nucleotide and deduced amino acid sequences of VP4, VP7, NSP1 and NSP3 of MP409
      with published sequences of strains belonging to different serotypes revealed
      that both outer capsid proteins VP4 and VP7 and NSPI are highly related to the
      respective proteins from the P6[1], G8 type bovine rotavirus A5 isolated from a
      calf with diarrhoea in Thailand and that the NSP3 is highly homologous to that of
      bovine rotaviruses. The NSP4 protein showed greatest sequence identity with NSP4s
      belonging to the KUN genetic group to which NSP4s from human G2 type strains and
      bovine rotaviruses belong. MP409 and MP480 likely signify interspecies
      transmission of P6[1], G8 type strains from cattle to humans and represent the
      first P6[1] type rotaviruses isolated in humans. These and our previous studies
      on the asymptomatic neonatal strain 1321 are of evolutionary and epidemiological
      significance in the context of close association of majority of the Indian
      population with cattle.

PMID- 10963342
TI  - Genomic variability of equine herpesvirus-5.
AB  - Seventeen New Zealand isolates of equine herpesvirus 5 (EHV-5) were compared to
      the Australian prototype strain. PCR primers were designed to amplify EHV-5
      glycoprotein B (gB) gene, and Restriction Fragment Length Polymorphism (RFLP) was
      used to detect differences between cloned PCR products. EHV-5 isolates from
      different horses showed a high degree of heterogeneity. However, EHV-5 isolates
      from individual horses remained homogeneous when examined over a period of time
      or isolated from different sites. A single EHV-5 gB RFLP profile was detected in
      isolates from each individual horse but one. Two or possibly three different
      genotypes of EHV-5 were detected in cultures inoculated with a nasal swab of this
      horse. The heterogeneity observed between EHV-5 isolates from different horses
      suggests that the use of RFLP may provide a useful epidemiological approach to
      gain more knowledge about the biology of EHV-5.

PMID- 10963343
TI  - Complete nucleotide sequence of Northern cereal mosaic virus and its genome
      organization.
AB  - We determined the complete nucleotide sequence, 13, 222 nucleotides (nts) of the
      Northern cereal mosaic virus (NCMV). The genome had 273 nt 5' trailer sequence
      and 90nts 3' leader sequence. It formed a terminal complementarity in 25 nts of
      both terminal sequences. A characteristic intergenic sequence (consensus)
      separating genes, 3'-AUUCUUUUUGACUCUAGU-5' was presented. The genome had nine
      open reading frames (ORFs) on the viral complementary sequence. Five putative
      proteins of NCMV were postulated by its molecular weight or comparison of the
      similarities to other rhabdovirus proteins: nucleocapsid (N), non-structural
      protein or phosphoprotein (P), matrix protein (M), glycoprotein (G), and
      polymerase (L). A series of four small ORFs (genes 3 to 6) were also presented
      between P and M gene sequences. The proposed NCMV genome organization was
      3'leader-N-P-3-4-5-6-M-G-L-5'trailer. N and L proteins of NCMV had low but
      distinct similarities to those of lettuce necrotic yellows virus and Sonchus
      yellow net virus, respectively.

PMID- 10963344
TI  - Identification of a novel 23kDa protein encoded by putative open reading frame 2
      of TT virus (TTV) genotype 1 different from the other genotypes.
AB  - We report the entire open reading frames (ORFs) sequences of four TT virus (TTV)
      isolates, one genotype 2 (G2) and three G4 isolates. Despite a DNA virus, TTV
      possesses high rate of amino acid (aa) substitution: the aa sequence homology of
      ORF1 and 2 is lower than the nucleotide homology. The partial 'N22' region of
      ORF1 is suitable for genotyping of 'prototype TTV' isolates, because the
      phylogenetic tree from partial 'N22' sequence is consistent with that from the
      entire ORF1. Based on our sequence data, ORF2 from most isolates excluding G1
      encode truncated 49 aa (pORF2a) because of an in-frame stop codon, although ORF2s
      from most G1 isolates encode 202 aa (pORF2ab). Just downstream the stop codon,
      another ORF encoding a protein of approximately 150 aa (pORF2b) is found, whose
      homology is quite low among these genotypes. Our in vitro
      transcription/translation study supports that all G1a and a part of G b without
      an in-frame stop codon dominantly encode pORF2ab, a novel 23 kDa protein, whereas
      the other genotypes with an in-frame stop codon encode pORF2b (17 kDa). Our data
      indicate TTV G1a and a part of G1b should have different characteristics from the
      other genotypes.

PMID- 10963345
TI  - Virologic and serologic surveillance for human, swine and avian influenza virus
      infections among pigs in the north-central United States.
AB  - Influenza virus infection in pigs is both an animal health problem and a public
      health concern. As such, surveillance and characterization of influenza viruses
      in swine is important to the veterinary community and should be a part of human
      pandemic preparedness planning. Studies in 1976/1977 and 1988/1989 demonstrated
      that pigs in the U.S. were commonly infected with classical swine H1N1 viruses,
      whereas human H3 and avian influenza virus infections were very rare. In
      contrast, human H3 and avian H1 viruses have been isolated frequently from pigs
      in Europe and Asia over the last two decades. From September 1997 through August
      1998, we isolated 26 influenza viruses from pigs in the north central United
      States at the point of slaughter. All 26 isolates were H1N1 viruses, and
      phylogenetic analyses of the hemagglutinin and nucleoprotein genes from 11
      representative viruses demonstrated that these were classical swine H1 viruses.
      However, monoclonal antibody analyses revealed antigenic heterogeneity among the
      HA proteins of the 26 viruses. Serologically, 27.7% of 2,375 pigs tested had
      hemagglutination-inhibiting antibodies against classical swine H1 influenza
      virus. Of particular significance, however, the rates of seropositivity to avian
      H1 (7.6%) and human H3 (8.0%) viruses were substantially higher than in previous
      studies.

PMID- 10963346
TI  - Reclassification of the Caliciviridae into distinct genera and exclusion of
      hepatitis E virus from the family on the basis of comparative phylogenetic
      analysis.
AB  - Caliciviridae and Picornaviridae belong to the same subphylum and genera within
      Picornaviridae are well characterized. Until 1998, Caliciviridae included one
      genus Calicivirus, containing strains with distinct structural and genomic
      features. Phylogenetic analyses of capsid genes revealed five clusters within
      Caliciviridae corresponding to differences in genome organization. In order to
      determine to what taxonomic level these clusters correspond, genomic sequences of
      caliciviruses, picornavirus prototypes, and two togavirus strains were analyzed.
      Distance and maximum likelihood methods were used to estimate the phylogenetic
      relationships among strains. Analysis of the capsid gene revealed separation of
      five main clusters (Norwalk-like, and Sapporo-like human caliciviruses, hepatitis
      E virus, vesicular exanthem of swine-like, and lapine caliciviruses) and
      distances corresponding to those observed among picornavirus genera. Utilizing
      more conserved (presumed helicase and polymerase) regions for the analyses, only
      major groups of caliciviruses were separated with confidence, with distances also
      comparable to those separating picornavirus genera. Analysis in these regions
      that included togavirus sequences moved HEV strains out of the calicivirus
      cluster. Our findings support the reclassification of caliciviruses into four
      genera. The phylogenetic position of hepatitis E virus, by analysis of non
      structural genes, is outside of the caliciviruses, in an uncertain taxonomic
      position.

PMID- 10963347
TI  - Cross-reactive and major virus-specific epitopes are located at the N-terminal
      halves of the cylindrical inclusion proteins of turnip mosaic and zucchini yellow
      mosaic potyviruses.
AB  - To investigate the antigenic nature of cylindrical inclusion proteins (CIPs) of
      the potyviruses Turnip mosaic virus (TuMV) and Zucchini yellow mosaic virus
      (ZYMV), monoclonal antibodies (MAbs) against the two CIPs were produced and
      epitopes on the CIPs were localized using Escherichia coli-expressed CIP
      fragments in Western blot analysis. All 23 MAbs against ZYMV CIP reacted only
      with ZYMV CIP. In contrast out of the 18 MAbs produced against TuMV CIP, 14 MAbs
      were TuMV CIP-specific while the remaining four MAbs cross-reacted with both
      CIPs. The four cross-reactive MAbs recognized two distinct epitopes in the N
      terminal half of TuMV CIP corresponding to amino acid residues 103-119 and 224
      237. Thirteen out of 14 TuMV CIP-specific MAbs recognized two distinct epitopes
      within residues 1-102 and 120-214, while the other one recognized an epitope
      within residues 301-644. On the other hand, 21 out of 23 ZYMV CIP-specific MAbs
      recognized epitopes within residues 1-118, while the remaining two recognized
      epitopes within residues 301-522. These results suggest that cross-reactive and
      major virus-specific epitopes are located at the N-terminal half of the
      respective CIPs.

PMID- 10963348
TI  - Host range and symptom variation of pseudorecombinant virus produced by two
      distinct bipartite geminiviruses.
AB  - Within the whitefly group only the species Bemisia tabaci (Gennadius) is the
      vector. Most whitefly-transmitted geminiviruses possess bipartite DNA genomes,
      DNAs A and B. Although they are closely related to each other, the production of
      viable pseudorecombinants between bipartite geminiviruses by reassortment of
      infectious cloned components is generally limited to strains of a particular
      virus. Following exchange of cloned genomic components of Sida golden mosaic
      virus (SiGMV/Hoyv) and Abutilon mosaic virus (AbMV), the pseudorecombinant
      viruses were infectious in various host plants. The symptom type of
      pseudorecombinant virus was in most cases determined by DNA B. However, in some
      host plants also DNA A of the pseudorecombinant virus was involved in the symptom
      phenotype.

PMID- 10963349
TI  - Genetic variability within the VP1 coding region of echovirus type 30 isolates.
AB  - Genetic relationships of the prototype Bastianni strain of 1958 and of 13
      echovirus type 30 (ECV30) isolates associated with meningitis cases in Germany
      during a period from 1966 to 1997 were investigated using direct sequencing of
      amplicons derived from a part of the capsid protein VP1 gene. Sequences were
      aligned both with each other and with known sequences of other type 30 echovirus
      strains. Phylogenetic analysis indicated that isolates investigated in this work
      fell into at least three genetic clusters apart from the prototype Bastianni
      strain. This suggests that genetically distinct groups of ECV30 variants have
      developed over time.

PMID- 10963350
TI  - Involvement of spindles of an entomopoxvirus (EPV) in infectivity of the EPVs to
      their host insect.
AB  - The biological function of entomopoxvirus (EPV) spindles (inclusion bodies that
      lack virions), has not been elucidated. We characterized the function of EPV
      spindles in the cupreous chafer, Anomala cuprea (Coleoptera: Scarabaeidae).
      Spheroids or spheroids mixed with spindles of Anomala cuprea EPV were
      administered per os to the A. cuprea larvae. A significant increase in
      infectivity was induced by the addition of spindles to the spheroids, strongly
      suggesting that the spindles play an important role in the infection of the host
      insect.

PMID- 10963351
TI  - Conformational changes during proteolytic processing of a picornavirus capsid
      proteins.
AB  - We have used synthetic peptide antibodies to probe conformational changes that
      occur during the cleavage cascade which generates the capsid proteins of a
      picornavirus. The initial translation product of 97 kDa, the precursor of all
      four structural proteins, is cleaved to form a 63 kDa fragment which, we show,
      has significantly different folding characteristics to both its larger parent and
      its products. We demonstrate that proteolytic cleavages as distant as 520
      residues from epitopes confer sufficiently large conformational changes as to
      render them unrecognisable. To our knowledge, this is the first demonstration of
      this phenomenon in the picornavirus system.

PMID- 10963352
TI  - Restriction fragment length polymorphism analysis of open reading frame 5 gene of
      porcine reproductive and respiratory syndrome virus isolates in Korea.
AB  - The genetic variability of porcine reproductive and respiratory syndrome virus
      (PRRSV) was studied by restriction fragment length polymorphism (RFLP) of
      polymerase chain reaction (PCR)-amplified fragments among 50 Korean isolates from
      open reading frame 5. All Korean PRRSVs were isolated from the field cases after
      the marketing of an U.S. ATCC VR2332-derived modified live PRRSV vaccine.
      Combining the restriction enzyme digestion patterns obtained with MluI, HincII,
      SacII, and HaeIII, we observed 19 distinct RFLP patterns. Seventeen out of 50
      PRRSV isolates (34%) exhibited the modified live PRRSV vaccine RFLP pattern. The
      genomic variations that have been identified in the present study seemed to
      represent characteristic features of the Korean PRRSV isolates. PCR-based RFLP
      analysis using several restriction enzymes provides a good genetic estimate for
      isolate differentiation.

PMID- 10963353
TI  - Identification of the products of the equine herpesvirus type 4 gI and gE genes.
AB  - In order to identify the products of the equine herpesvirus type 4 (EHV-4) gI and
      gE genes, we have constructed recombinant vaccinia viruses containing the
      putative gI or gE genes. These recombinant viruses synthesized EHV-4 gI and gE
      with apparent molecular masses of 75 and 80kDa, respectively. Antibodies raised
      against both recombinant viruses detected a 75 kDa gI and a 95 kDa gE in EHV-4
      infected cells. The results also suggest that the EHV-4 gI and gE would form a
      complex like in other herpesviruses.

PMID- 10963354
TI  - The current composition of ICTV. International Committee on Taxonomy of Viruses.

PMID- 10963355
TI  - Virus nomenclature descending into chaos.

PMID- 10963356
TI  - Sequestration of iron by Lewy bodies in Parkinson's disease.
AB  - Central to the oxidative stress hypothesis of Parkinson's disease (PD)
      pathogenesis is the ability of iron to generate hydroxyl radicals via the Fenton
      reaction, and the consistent demonstration of iron elevation in the pars compacta
      region of the substantia nigra. However, uncertainty exists as to whether the
      excess iron exists in a state suitable for redox chemistry. Here, using a method
      we developed that detects redox-active iron in situ, we were able to demonstrate
      strong labeling of Lewy bodies in substantia nigra pars compacta neurons in PD.
      In contrast, cortical Lewy bodies in cases of Lewy body variant of Alzheimer's
      disease were unstained. While the presence of elevated iron in PD substantiates
      the oxidative stress hypothesis, one must remember that these are viable neurons,
      indicating that Lewy bodies may act to sequester iron in PD brains in a
      protective, rather than degenerative, mechanism. The absence of redox-active iron
      in neocortical Lewy bodies highlights a fundamental difference between cortical
      and brain stem Lewy bodies.

PMID- 10963358
TI  - Neurofilament H immunoreaction in oligodendrogliomas as demonstrated by a new
      polyclonal antibody.
AB  - We have characterized a new polyclonal antibody against heavy chain (H) of
      neurofilament which can be used to demonstrate neurofilament H in normal brain
      tissue and oligodendroglioma cells immunocytochemically and immunochemically.
      Using this antibody we found neurofilament H-immunoreactive tumor cells in 13
      oligodendrogliomas (6 WHO grade II, 7 WHO grade III) out of 84 oligodendrogliomas
      investigated (59 WHO grade II and 25 WHO grade III). Double immunolabeling and
      confocal laser scanning microscopy showed colocalization of neurofilament H and
      glial fibrillary acidic protein in certain oligodendroglioma cells.
      Colocalization of neurofilament and synaptophysin was observed only rarely. The
      results support the notion that oligodendrogliomas consists of a heterogeneous
      cell population displaying various stages of differentiation and
      dedifferentiation. The occurrence of neurofilament H-immunoreactive tumor cells
      in oligodendrogliomas is not related to the survival of the patients.

PMID- 10963357
TI  - NACP/alpha-synuclein and tau constitute two distinctive subsets of filaments in
      the same neuronal inclusions in brains from a family of parkinsonism and dementia
      with Lewy bodies: double-immunolabeling fluorescence and electron microscopic
      studies.
AB  - The co-localization of NACP/alpha-synuclein and tau epitopes was examined in the
      brain stem and hippocampal formation in two patients from a family of autosomal
      dominant parkinsonism and dementia with Lewy bodies (LBs) without two reported
      missense mutations in the NACP gene. Double-labeling immunofluorescence study
      revealed that some brain stem LBs, cortical LBs, pale bodies, Lewy-related
      neurites, and neurofibrillary tangles expressed both NACP epitopes and the PHF
      tau AT8 epitope. Double-immunolabeling electron microscopy demonstrated that the
      NACP antibody selectively labeled 9- to 13-nm-thick straight filaments (LB
      filaments), whereas AT8 recognized twisted tubules with 80-to 100-nm-interval
      constrictions in the same neuronal inclusions. We show that NACP and tau
      aggregate into different filamentous components even if both proteins are
      incorporated into the same inclusions.

PMID- 10963359
TI  - Glial cell line-derived neurotrophic factor-like immunoreactivity in the
      cerebella of normal subjects and patients with multiple system atrophy.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has a trophic effect on
      various types of neurons, including cerebellar Purkinje cells. To investigate the
      role of GDNF in the human cerebellum, we examined the cerebella of eight control
      cases and eight patients with multiple system atrophy (MSA) immunohistochemically
      using a polyclonal anti-GDNF antibody. The antibody recognized a single band of
      approximately 34 kDa on Western blot analysis of human cerebellar homogenates. In
      the cerebella from normal subjects, the neuronal somata and dendrites of the
      Purkinje cells were immunostained intensely, as were some axons, including
      torpedoes, immunolabeled in the granular layer. Many axons and a few
      oligodendrocytes were also immunopositive in the white matter, and weak
      immunoreactivity was detected in the granule cells and neurons in the cerebellar
      nuclei. In the cerebella from patients with MSA, the general immunostaining
      pattern was similar to that observed in the normal subjects. Most of the
      remaining Purkinje cells showed strong immunoreactivity, and abundant GDNF
      positive granular structures or dense arborizations of GDNF-positive dendrites
      were found in some areas of the molecular layer. These data suggest that GDNF may
      be mainly produced and localized in the Purkinje cells of the human cerebellum,
      even in patients with MSA, and that the functional impairment of the Purkinje
      cells of MSA patients might cause a focal accumulation of GDNF in the dendrites
      of some of the surviving Purkinje cells.

PMID- 10963360
TI  - Excitatory amino acid transporter 1 and 2 immunoreactivity in the spinal cord in
      amyotrophic lateral sclerosis.
AB  - The spinal cord of 20 patients with amyotrophic lateral sclerosis (ALS) and 5
      patients with lower motor neuron disease (LMND) were investigated
      immunohistochemically using anti-human excitatory amino acid transporter 1
      (EAAT1) and EAAT2 antibodies which are the astrocytic transporters. The purpose
      of the study was to examine relationships between EAAT1 and EAAT2
      immunoreactivity and degeneration of anterior horn neurons. Specimens from 20
      patients without any neurological disease served as controls. In controls, spinal
      cord gray matter was densely immunostained by antibodies, whereas the white
      matter was generally not immunostained. In motor neuron disease (MND) patients,
      EAAT1 immunoreactivity was relatively well preserved in the gray matter despite
      neuronal loss of anterior horn cells. On the other hand, EAAT2 immunoreactivity
      in anterior horns correlated with the degree of neuronal loss of anterior horn
      cells: in the patients with mild neuronal depletion, anterior horns were densely
      immunostained by the antibody, whereas in the patients with severe neuronal loss,
      EAAT2 expression was markedly reduced. Degenerated anterior horn cells frequently
      showed a much denser EAAT1 and EAAT2 immunoreactivity around the surface of the
      neurons and their neuronal processes than that observed in normal-appearing
      neurons. There was no difference in the expression of EAAT1 and EAAT2
      immunoreactivity between LMND and ALS patients. These findings suggest that in
      the early stage of degeneration of anterior horn cells, EAAT1 and EAAT2
      immunoreactivity is preserved in the astrocytic foot directly attached to normal
      appearing neurons, whereas levels of EAAT1 and EAAT2 protein rather increase in
      the astrocytic foot directly attached to degenerated anterior horn neurons; the
      latter effect most probably reduces the elevated glutamate level, compensates for
      the reduced function of astroglial glutamate transporters, or represents a
      condensation of EAAT1 and EAAT2 immunoreactivity secondary to loss of neurites
      and greater condensation of astrocytic processes. Thus, we demonstrate a
      difference in EAAT1 and EAAT2 immunoreactivity in different stages of progression
      in ALS, as a feature of the pathomechanism of this disease.

PMID- 10963362
TI  - Different expression of calreticulin and immunoglobulin binding protein in
      Alzheimer's disease brain.
AB  - Both calreticulin (CRT) and immunoglobulin binding protein (Bip) have a role in
      the folding and assembly of oligomeric membrane proteins in the endoplasmic
      reticulum (ER). Recent studies have demonstrated the generation of beta-amyloid
      protein (Abeta) 1-42, a key peptide for amyloid deposits, in the ER. We,
      therefore, examined the localization and expression of CRT, Bip and their mRNA by
      immunohistochemistry, Western blot, in situ hybridization and semiquantitative
      reverse transcription polymerase chain reaction (RT-PCR) in both neurologically
      normal and Alzheimer's disease (AD) brains. Two polyclonal anti-CRT antibodies
      gave similar positive staining of CRT in neurons and glia. In neuronal cells, the
      cytoplasm, nucleoli and their processes were positive for CRT. In glial cells,
      perinuclear staining was frequently seen and the processes of some glial cells
      were also stained. In AD, these antibodies stained clearly damaged neurons but
      the number and the intensity of positive cells were decreased compared to
      controls. Processes of microglial cells were markedly positive in the AD white
      matter. Western blots using an anti-CRT antibody showed significantly lower
      immunoreactive bands in AD than control brains. By in situ hybridization, the
      number of neurons which express the CRT mRNA was less in AD than in controls.
      Using RT-PCR, the relative levels of the CRT mRNA in AD brains were also found to
      be significantly lower than those in controls. On the other hand, the number of
      Bip-positive cell, the production of Bip and the expression of mRNA for Bip did
      not differ between control and AD brains. These results suggest that CRT may be a
      multifunctional protein in human brain, and that the weak expression of CRT and
      the positive staining of microglial processes in AD brain may be part of the
      pathological processes in AD.

PMID- 10963361
TI  - Lewy body and Alzheimer pathology in a family with the amyloid-beta precursor
      protein APP717 gene mutation.
AB  - Mutations in the amyloid precursor protein (APP) gene cause one form of early
      onset familial Alzheimer's disease (AD). One such family has been studied
      genetically and neuropathologically and represents the basis of the present
      report. Four siblings with the APP717 Val to Ile mutation, aged 59, 65, 61 and 64
      years, apolipoprotein E (APOE) genotyped 2,4 (first three) and 2,3 respectively,
      had severe AD, Braak stage VI with frequent neurofibrillary tangles in the
      primary visual cortex, Brodmann area 17. The first one also met McKeith criteria
      for the limbic stage of dementia with Lewy bodies but did not have substantia
      nigra Lewy bodies. The second two met McKeith criteria for the neocortical stage
      of dementia with Lewy bodies and both had substantia nigra Lewy bodies. The
      fourth had AD but no Lewy bodies. A cousin without the APP717 mutation who was
      APOE 3, 4, developed dementia at age 60 and died at age 75. She had severe
      cerebrovascular atherosclerosis, less severe AD, Braak stage V, with sparing of
      area 17. She also had Lewy bodies in the substantia nigra and in the cortex and
      met McKeith criteria for neocortical stage of dementia with Lewy bodies.
      Extrapyramidal features were present in all five. Lewy bodies have been described
      in 53% of reported autopsies on individuals with the APP717 Val to Ile mutation
      coincident with dementia and AD neuropathologic changes. These observations
      suggest an association between the chromosome 21 APP mutation and Lewy body
      formation, possibly mediated by other environmental or genetic factors.

PMID- 10963363
TI  - Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia
      induced brain injury in neonatal rat.
AB  - Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly
      attenuated in a dose-dependent manner by intracerebral injection of glial cell
      line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the
      insult. Whereas the great majority of the vehicle-treated animals showed massive
      infarction involving more than 75% of the affected cerebral hemisphere, GDNF
      injection resulted in a remarkable reduction in both the incidence and severity
      of the brain damage (incidence ranging from 76% to 93% in controls to 34% to 64%
      in the 2.0-microg group and 7% to 29% in 4.0-microg group). The induction of
      immunoreactive 70-kDa heat shock protein (HSP70) in cerebral cortical neurons was
      also significantly reduced in GDNF-treated animals as compared to controls. The
      mechanisms responsible for the neuroprotective effects of GDNF remain unknown,
      although it has been speculated that these may be endogeneous. The higher
      expression of GDNF and its mRNA in developing brains may be one of the factors
      responsible for the relative resistance to ischemia of fetal and neonatal as
      opposed to adult brains. GDNF may possibly act by protecting against oxidative
      stress or by scavenging free radicals generated during ischemia. The results of
      our study strongly suggest that GDNF may prove to be an effective and potent
      protective agent against perinatal ischemic/hypoxic encephalopathy.

PMID- 10963365
TI  - A neuropathological analysis of experimental autoimmune encephalomyelitis with
      predominant brain stem and cerebellar involvement and differences between active
      and passive induction.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune demyelinating
      disease that can be induced in a variety of animal species and which is commonly
      used as an animal model of multiple sclerosis. In rodent EAE models, the clinical
      disease is typified by ascending paralysis; however, other clinical patterns can
      also be observed by inducing disease with particular peptides of myelin
      proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein. Here we
      describe EAE induced in C3H/HeJ mice by inoculation with residues 190-209 of PLP.
      This form of EAE is manifested clinically by a movement disorder, with axial
      rotation of the head and trunk. Histologically, this form of EAE is characterized
      by predominant cerebellar or brain stem involvement, depending on whether EAE is
      induced by active immunization with the PLP peptide, or by passive transfer of T
      cells specific for the peptide. The inflammatory cell infiltrate is composed of
      polymorphonuclear cells and mononuclear cells. This rotatory form of EAE may be a
      useful model for studying the neuropathological characteristics of multiple
      sclerosis affecting the brain stem and cerebellum.

PMID- 10963364
TI  - A novel migration-related gene product, doublecortin, in neuronal migration
      disorder of fetuses and infants with Zellweger syndrome.
AB  - Immunohistochemical expression of doublecortin (DCX), KIAA0369 (KIA) and LIS1
      proteins as well as nestin and vimentin in the cerebral cortices of six patients
      with Zellweger syndrome (ZS), aged 19 gestational weeks (GW) to 8 months, was
      compared with that in nine controls, aged 12 GW to 8 months. DCX immunoreactivity
      was apparently reduced in ZS, particularly in the cortical plate of fetuses, and
      in the subependymal foci of heterotopic neurons of the infants. Reduced
      expression of DCX in ZS was confirmed by Western blot analysis. On the other
      hand, neuronal expression of nestin was high in the cortical plate, migrating
      cells of the white matter and germinal cells in the ventricular zone in fetuses
      with ZS. Immunoreactivities for KIA, LIS1 and vimentin in ZS were comparable to
      those of controls. Reduced expression of DCX may be responsible for the neuronal
      migration disorder, and increased expression of nestin may be another evidence
      for delayed neuronal maturation in ZS.

PMID- 10963366
TI  - The effects of taxol on the central nervous system response to physical injury.
AB  - Cytoskeletal disruption is a key pathological change in numerous human
      neurodegenerative diseases. We have, therefore, examined the effect of taxol, a
      microtubule-stabilising agent, on the neuronal response to localised trauma in
      the central nervous system utilising a rodent experimental model that replicates
      cytoskeletal alterations which occur in conditions such as Alzheimer's disease
      and head injury. At 1 day post-injury, 1 mM taxol administration to the damaged
      neocortex resulted in a statistically significant reduction in the density of
      abnormal neurites labelled with antibodies to neurofilaments. In addition, there
      was a relative preservation of MAP2 labelling of dendrites surrounding the injury
      site in taxol-treated, as compared to vehicle-treated, animals at 1 day post
      injury. At 4 days post-injury, however, there was a statistically significant
      increase in the density of abnormal neurites surrounding the injury site in taxol
      treated rats as compared to vehicle-treated animals. The degree of MAP2 labelling
      was also equally decreased in both vehicle- and taxol-treated animals as compared
      to normal cortex at this time point. Our data suggest that, in the short term,
      taxol may be stabilising neuronal microtubules and reducing reactive alterations
      in axons. After longer periods, however, our data indicate that the stereotypical
      neuronal reaction to trauma may be abnormally prolonged due to taxol
      administration, consistent with both in vivo work on taxol intoxication in the
      injured peripheral nervous system and in vitro culture studies.

PMID- 10963367
TI  - Neural substrates of spatial and temporal disorientation in Alzheimer's disease.
AB  - To examine the neuroanatomical correlates of spatial and temporal disorientation
      in Alzheimer's disease (AD), we performed an anterograde clinicopathological
      study of 29 patients with clinically and neuropathologically confirmed AD.
      Spatial and temporal disorientation was assessed using the locational orientation
      subtests of the Mini Mental State Examination and the Benton's test for temporal
      orientation. Quantitative analysis of neurofibrillary tangles and senile plaques
      were performed in the CA1 field of the hippocampus, layers II and V of the
      entorhinal cortex, and layers II-III and V-VI of areas 9, 7, 39, 19, 37, 20 and
      23 in the right hemisphere. Forward stepwise logistic regression was used to
      assess the relationship between lesion densities and the presence of either
      spatial or temporal disorientation; severity scores and brain weight were
      included as covariants. A statistically significant relationship was found
      between neurofibrillary tangle densities in Brodmann's areas 7, 23 and the CA1
      field of hippocampus and both spatial and temporal disorientation. Senile plaque
      counts did not correlate with any of the neuropsychological parameters. Both
      temporal and spatial disorientation in AD are related to the degeneration of the
      same pathways linking the hippocampus with the superior parietal and posterior
      cingulate cortex in the right hemisphere. These observations are discussed with
      respect to the notion of global corticocortical disconnection in AD.

PMID- 10963369
TI  - Distribution of chromogranin B-like immunoreactivity in the human hippocampus and
      its changes in Alzheimer's disease.
AB  - Synapse loss is crucially involved in cognitive decline in Alzheimer's disease
      (AD). This study was performed to investigate the distribution and density of
      chromogranin B-like immunoreactivity in the hippocampus of control compared to AD
      brain. Chromogranin B is a large precursor molecule found in large dense-core
      vesicles. For immunocytochemistry we used an antiserum raised against a synthetic
      peptide (PE- 11) present in the chromogranin B molecule. Chromogranin B-like
      immunoreactivity was concentrated in the terminal field of mossy fibers, the
      inner molecular layer of the dentate gyrus and in layer II of the entorhinal
      cortex. In AD, chromogranin B was detected in neuritic plaques. The density of
      chromogranin B-like immunoreactivity was significantly reduced in the inner
      molecular layer of the dentate gyrus and in layers II, III and V of the
      entorhinal cortex in AD brains. The present study demonstrates that chromogranin
      B is a marker for human hippocampal pathways. It is particularly suitable for
      studying nerve fibers terminating at the inner molecular layer of the dentate
      gyrus. It is present in neuritic plaques, and its density is reduced in a layer
      specific manner.

PMID- 10963368
TI  - Expression of the inducible nitric oxide synthase in distinct cellular types
      after traumatic brain injury: an in situ hybridization and immunocytochemical
      study.
AB  - The Marmarou's acceleration traumatic brain injury (TBI) model, in situ
      hybridization and immunocytochemistry were utilized to study the temporal
      expression of the inducible form of nitric oxide synthase (iNOS) mRNA and protein
      in different cellular compartments of the rat brain. Four hours following TBI,
      expression of iNOS was observed in the endothelial cells of cerebral blood
      vessels, macrophages and many cortical and hippocampal neurons. In the cortex
      labeled neuronal and nonneuronal cells were primarily found in the superficial
      layers. In the hippocampus the strongest neuronal labeling was observed in the
      CAI and CA3 (lateral part) regions. By 24 h post TBI endothelial cells no longer
      expressed iNOS mRNA, and the macrophage and neuronal iNOS expression was reduced
      by 30-50%. The reduction was assessed by automated quantitation of the silver
      grains that occupy individual cellular profiles using an image analysis system.
      Immunocytochemistry revealed de novo iNOS synthesis in non-neuronal cells at the
      different time points, thus paralleling the changes in iNOS mRNA expression. In
      contrast, iNOS immunoreactivity in neurons was not observed before 24 h post TBI,
      suggesting failure of iNOS protein translation at 4 h after trauma. The results
      demonstrate complex spatial and temporal patterns of iNOS expression in discrete
      cellular populations, indicating different times of nitric oxide synthesis (and
      release) following TBI. Uncoupling of iNOS mRNA and protein synthesis in neurons
      suggests differential synthesis of nitric oxide in these cells as compared to non
      neuronal cellular populations after trauma.

PMID- 10963370
TI  - Neuropathology and general autopsy findings in AIDS during the last 15 years.
AB  - A retrospective study of 450 consecutive AIDS autopsy cases (397 males, 53
      females; mean age at death 38.4 years) in Vienna, Austria, between 1984 and 1999
      compares the central nervous system (CNS) findings in three cohorts: 1984-1992
      (190 cases), 1993-1995 (162 cases) and 1996-1999 (98 cases, after introduction of
      triple antiretroviral therapy) and the relationship of CNS findings to systemic
      AIDS pathology in the latter two cohorts. In these two groups, following
      involvement of the lung (85% and 75%, respectively), the brain continued to be
      the second most frequently involved organ (decrease from 80% to 60%,
      respectively). Extracerebral protozoal (Pneumocystis carinii, toxoplasmosis),
      Mycobacterium avium complex, viral [e.g., cytomegalovirus (CMV)], multiple
      opportunistic organ and CNS infections, and Kaposi sarcoma significantly
      decreased over time. There was less decrease in fungal infections, while
      bacterial organ and CNS infections (except for mycobacteriosis), lymphomas, HIV
      associated CNS lesions (around 30%), non HIV-associated changes (vascular,
      metabolic, etc.) and negative CNS findings (10-11%) remained unchanged.
      Nonspecific CNS changes (e.g., meningeal fibrosis) increased. Extracerebral
      pathology in subjects with advanced HIV-related CNS lesions showed more frequent
      but decreasing systemic bacterial and CMV infections than those with negative or
      nonspecific neuropathology, while other opportunistic and multiple organ
      infections and lymphomas showed no differences between both groups. In a cohort
      of drug abusers, HIV encephalitis, progressive multifocal leukoencephalopathy,
      bacterial infections, hepatic encephalopathy, and negative CNS findings were more
      frequent than in non-users who showed increased incidence of CMV, toxoplasmosis,
      or other opportunistic CNS infections, and nonspecific CNS findings; the
      frequency of lymphomas was similar in both drug abusers and non-users. Similar to
      a recent autopsy study from San Diego, these data suggest that despite the
      beneficial effects of modern antiretroviral combination therapy, involvement of
      the brain in AIDS subjects continues to be a frequent autopsy finding, while the
      increased incidence of HIV encephalitis in our small cohort of drug users was
      less than observed in other recent autopsy studies.

PMID- 10963371
TI  - Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in rapidly
      progressive motor neuron disease: immunohistochemical and electron microscopic
      studies.
AB  - In an autopsy case of sporadic rapidly progressive lower motor neuron disease
      (MND), Gallyas-positive argyrophilic and ubiquitinated filamentous
      intracytoplasmic inclusions were found in the neurons. Clinically, 7 months prior
      to death, a 68-year-old woman experienced a history of rapidly progressive muscle
      weakness of all four extremities and bulbar sign, without sensory and autonomic
      disturbance. Two months later, she became unable to stand or walk. Four months
      after onset, she needed respiratory support, and subsequently died due to
      cardiorespiratory arrest. Neuropathological examinations revealed neuronal loss
      and associated gliosis in the lower motor neurons, except for ocular motor
      nuclei, Clark's column, and accessory cuneate nucleus, and tract degeneration was
      observed in the middle root zone of the posterior column and spinocerebellar
      tract. No Bunina bodies or Lewy body-like hyaline inclusions were found in the
      anterior horns. Gallyaspositive argyrophilic filamentous inclusions were found in
      the lower motor neurons and in nerve cells of the Clark's column, intermediate
      zone, posterior horn and accessory cuneate nucleus. These were positive with anti
      ubiquitin antibody but negative with anti-tau (tau-2 and AT8) and neurofilament
      antibodies. Electron microscopic examinations disclosed randomly arranged tubular
      like filamentous profiles, with a diameter of 12-14 nm, sometimes with amorphous
      granules in the perikaryon. This is the first report on the Gallyas-positive
      argyrophilic and ubiquitinated filamentous inclusions in neurons in MND.

PMID- 10963372
TI  - Suprasellar germinoma in three lake whitefish (Coregonus clupeaformis).
AB  - Suprasellar germinomas were identified in three wild-caught lake whitefish
      (Coregonus clupeaformis) from the St. Lawrence River, Quebec, Canada.
      Histologically, the three tumors expanded the subarachnoid space of the ventral
      surface of the brain immediately adjacent to the pituitary gland and, in one
      case, infiltrated the adjacent neuropil. These tumors were characterized by nests
      and sheets of round cells with a high mitotic rate, separated by a scant amount
      of loose fibrovascular stroma. The stroma was infiltrated by a moderate number of
      small mononuclear cells, including rare CD3-immunoreactive lymphocytes. This is
      the first report of intracranial germinoma in a fish species.

PMID- 10963373
TI  - A case of sporadic Creutzfeldt-Jakob disease with a Gerstmann-Straussler
      Scheinker phenotype but no alterations in the PRNP gene.

PMID- 10963374
TI  - Telomeres, telomerase and cancer: an up-date.
AB  - In the mid 1990s, the hypothesis emerged that the upregulation or re-expression
      of a telomere-synthesising ribonucleoprotein, called telomerase, is a critical
      event responsible for continuous tumour cell growth. In contrast to normal cells,
      in which gradual mitosis-related erosion of telomeres eventually limits
      replicative life span, tumour cells have telomerase and show no loss of these
      chromosomal ends. These data suggest that telomere stabilisation may be required
      for cells to escape replicative senescence and to proliferate indefinitely.
      Because of the close association between telomerase and malignancy, both
      pathologists and clinicians expect this molecule to be a useful malignancy-marker
      and a new therapeutic target. This review focuses on the components of the human
      telomere and of the human telomerase enzyme. A synopsis of reports studying the
      clinical-diagnostic value of telomere length measurements, of telomerase activity
      analyses and of the in situ telomerase detection is given. Finally, a summary of
      recent experimental work that sheds new light on the biological role of this
      fascinating molecule is presented.

PMID- 10963375
TI  - Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by
      cell proliferation and apoptosis.
AB  - Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally
      found in the colorectum. To clarify whether cell kinetic status affects the
      macroscopic morphology of colorectal neoplasms, we investigated proliferative
      indices (PI), apoptotic indices (AI), and the expression of apoptosis-related
      gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38
      flat elevated and 36 depressed tumours. According to WHO's criteria these tumours
      consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high
      grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells
      were detected by TUNEL staining. Proliferating cells and apoptosis-related gene
      products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax
      antigens. AI were closely associated with macroscopic morphology in adenomas but
      not in carcinomas. PI were relatively constant among the three macroscopic types
      in adenomas and carcinomas. Median AI values of polypoid, flat elevated and
      depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and
      6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively.
      Overall PI were significantly higher in carcinomas than in adenomas with LGD,
      whereas AI were not different. Although the incidence of expression was
      significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the
      others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax)
      was similar among polypoid, flat elevated and depressed tumours. Macroscopic
      morphology of colorectal adenomas is determined by the apoptosis not by
      proliferation, and high apoptosis found in depressed adenomas implies their low
      net growth.

PMID- 10963376
TI  - Overexpression of MDM2 protein in intrahepatic cholangiocarcinoma: relationship
      with p53 overexpression, Ki-67 labeling, and clinicopathological features.
AB  - Aberration of the p53 gene is thought to be the most frequent genetic alteration
      in human cancers. Tp53 protein may be inactivated by the binding of the MDM2
      protein. MDM2, the product of the mdm2 gene, is an oncoprotein that binds to Tp53
      and inhibits the p53-mediated transactivation. MDM2 overexpression has been
      reported in several human cancers, but not in intrahepatic cholangiocarcinoma
      (ICC). Therefore, we have evaluated the immunohistochemical overexpression of
      MDM2 and the relationship between its expression and histological grade,
      clinicopathological features, Tp53 overexpression, and Ki-67 labeling index in 47
      cases of ICC. MDM2 and Tp53 were found to be overexpressed in 38% and 57% of the
      tumor, respectively. MDM2 and Tp53 were not expressed in non-tumorous liver
      tissue. There was no significant difference between the MDM2 overexpression and
      ICC tumor grade. However, MDM2 overexpression correlated with the presence of
      metastases (P<0.01) and advanced tumor stage (P<0.05). MDM2 overexpression also
      correlated with Tp53 overexpression (P<0.03) and Ki-67 labeling index (P<0.03).
      Our findings suggest that MDM2 overexpression may play a role in the late stage
      of human ICC.

PMID- 10963377
TI  - Thymidine phosphorylase expression results in a decrease in apoptosis and
      increase in intratumoral microvessel density in human gastric carcinomas.
AB  - Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth
      factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas
      than in adjacent normal tissue. The higher expression is associated with an
      increase in intratumoral microvessel density (IMVD) and an unfavorable patient
      prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53
      expression in human gastric carcinomas, dThdPase expression was noted in 12
      (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At
      least 10 areas consisting of carcinoma cells with diffuse dThdPase expression
      from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase
      expression from the 38 negative tumors (category II) were selected from each
      case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I
      and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma,
      the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II
      carcinomas. The mean IMVD was significantly higher in category I than in category
      II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells)
      was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for
      early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in
      category II carcinomas for advanced gastric carcinoma, the value of the mean AI
      being significantly (P<0.05) higher in dThdPase-negative tumors (category II)
      than in the positive tumors (category I), regardless of tumor stage or
      histological type. There was a significant inverse correlation (P<0.001) between
      AI and IMVD. These results indicate that dThdPase expression is associated with
      both an increase in intratumoral microvessels and a decrease in apoptosis in
      human gastric carcinomas.

PMID- 10963378
TI  - Significant increase in antigastric autoantibodies in a long-term follow-up study
      of H. pylori gastritis.
AB  - In 30% of H. pylori-infected patients a certain type of antigastric
      autoantibodies, reacting against canalicular structures within human parietal
      cells, is detectable. Furthermore, it has been shown that these autoantibodies
      are correlated with atrophy of the mucosa in the corpus. The aim of this study
      was to analyse the prevalence of these anticanalicular autoantibodies (ACAB) and
      their significance for development of gastric mucosa atrophy in a 12-year follow
      up period. Gastric biopsy specimens from 62 persons in Saaremaa Island, Estonia,
      were collected in 1997 and assessed independently by two pathologists in
      accordance with the updated Sydney system. The sera of these persons were
      immunohistochemically screened for ACAB and for classic parietal cell antibodies
      (PCA). In addition, for 37 of the 62 persons, gastric biopsies and sera collected
      12 years earlier (1985) were investigated in an analogous manner. ACAB increased
      significantly, from 8 out of 37 in 1985 to 17 out of 37 in 1997 (P=0.004; McNemar
      test). In 1997 a significant correlation existed between the presence of ACAB and
      corpus mucosa atrophy (19 out of 30 versus 10 out of 32 without atrophy; P=0.01;
      odds ratio (OR)=3.8, 95% CI 1.4-10.6). However, no correlation was found between
      ACAB and development of atrophy in the period from 1985 to 1997. All 37 persons
      were PCA negative in 1985, whereas in 1997, 2 turned out to be PCA positive. ACAB
      increased significantly with duration of H. pylori gastritis. The correlation
      between ACAB and presence of gastric corpus atrophy was confirmed. However, it is
      possible that ACAB are the consequence of and not a causative factor in gastric
      mucosa atrophy, insofar as the association of ACAB with progression of corpus
      atrophy was not significant.

PMID- 10963379
TI  - Quality assessment in diagnostic molecular pathology: experience from a German
      Austrian-Swiss multicenter trial.
AB  - In order to assess the current technical standard of diagnostic molecular
      pathology, we have conducted a multicenter trial with 34 participating pathology
      laboratories in Germany, Austria and Switzerland. Formalin-fixed, paraffin
      embedded tissue blocks were selected from 15 cases, comprising 4 B-cell non
      Hodgkin's lymphomas, 4 T-cell non-Hodgkin lymphomas, 4 cases with lymphadenitis,
      2 cases with confirmed tuberculosis and 1 case of sarcoidosis. All participating
      laboratories received one 10-microm section from each of the 15 cases to detect
      clonality using immunoglobulin heavy chain (IgH) gene or T-cell receptor (TCR)
      gamma gene rearrangement analysis in 12 and mycobacterial DNA in 3 cases. In
      addition, participants had to answer technical questions about the application of
      internal quality controls and performance of fragment length or sequence
      analysis. Correct results were reported in 80% and 90% for IgH and TCR-gammagene
      rearrangement analysis, respectively, and in 83% for mycobacterial DNA analysis.
      No significant differences in the quality of results were obvious when the
      individual techniques used for molecular analysis were compared. However, when
      two independent techniques were used by the same laboratory, a higher rate of
      correct results was obtained for IgH and TCR rearrangement analysis. In
      conclusion, this study demonstrates a high technical standard of molecular
      diagnostic adjuncts among the participating laboratories. Regular multicenter
      trials with a greater number of participating laboratories working in this field
      will be indispensable to ensure a continuing or increasing standard in diagnostic
      molecular pathology.

PMID- 10963380
TI  - The validity of telepathological frozen section diagnosis with ISDN-mediated
      remote microscopy.
AB  - We investigated 109 randomly selected frozen section specimens from lung surgery
      patients in a retrospective blind mode using telepathology equipment. The
      telepathology system applied (HISTKOM) used one ISDN B-channel and telemicroscopy
      with a remotely operated robotic microscope. The performance of telepathological
      frozen section diagnosis was compared with that of conventional frozen section
      diagnosis. The false-positive rate achieved was identical for both methods. The
      sensitivity (P=0.03), but not the specificity, was significantly lower for the
      telepathological method. The time needed to establish a diagnosis with the remote
      microscope was too high; therefore, upgrading to multichannel technology is
      recommended. The quality of the images transmitted was judged to be sufficient by
      the pathologists involved in the study. In conclusion, with further technical
      improvements in telemicroscopy and additional experience in telepathology, remote
      diagnosis seems to be feasible.

PMID- 10963381
TI  - Keratin 14 immunoreactive cells in pleomorphic adenomas and adenoid cystic
      carcinomas of salivary glands.
AB  - Our recent study of developing myoepithelial cells (MECs) in rat salivary glands
      demonstrated that developing MECs begin to express alpha-smooth muscle actin
      (alphaSMA) first and, thereafter, keratin 14. Therefore, it is unlikely that duct
      basal cells expressing keratin 14 alone are immature or undifferentiated MECs. In
      this study we carried out immunohistochemistry of pleomorphic adenomas and
      adenoid cystic carcinomas including normal salivary glands using monoclonal
      antibodies to keratin 14, smooth muscle proteins and keratin 19. The smooth
      muscle proteins examined included alphaSMA, h-caldesmon and h1-calponin; h1
      calponin was observed in keratinocytes and nerve fibers, indicating that the
      protein is not specific to smooth muscle, whereas alphaSMA and h-caldesmon turned
      out to be highly specific markers for smooth muscle cells in normal tissues. In
      normal glands, MECs were positive for both keratin 14 and smooth muscle proteins
      (alphaSMA and h-caldesmon). Non-MEC cells were essentially devoid of smooth
      muscle proteins. Non-MEC duct basal cells expressed keratin 14 with or without
      keratin 19, and luminal cells keratin 19 with or without keratin 14. This
      suggests that the keratin 14-positive, smooth muscle proteins-negative duct basal
      cells are luminal cell progenitors. Luminal cells in tubular structures of both
      tumors were positive for keratin 19 with or without keratin 14. Nonluminal
      peripheral cells of pleomorphic adenomas were mostly positive for keratin 14, and
      a small fraction of them expressed smooth muscle proteins. Conversely, peripheral
      cells of adenoid cystic carcinomas were mostly positive for smooth muscle
      proteins, and some of them expressed keratin 14. These results strongly suggest
      (1) that the luminal cell progenitors transform into major constituents of
      pleomorphic adenoma cells with keratin 14 but not smooth muscle proteins, and (2)
      that the peripheral cells of adenoid cystic carcinoma are derived from
      undifferentiated MECs. Solid structures of pleomorphic adenomas were formed by
      proliferation of the peripheral cells. MECs were observed only occasionally in
      the periphery. Solid and cribriform structures of adenoid cystic carcinomas were
      formed by proliferation of the luminal cells. MECs were observed in the periphery
      and around the pseudocyst.

PMID- 10963382
TI  - Alterations in extracellular matrix components in transplant glomerulopathy.
AB  - The distribution pattern of extracellular matrix (ECM) components in transplant
      glomerulopathy was studied in relation to light microscopic features, actin
      expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases
      of mild (group I) and nine cases of severe (group II) transplant glomerulopathy
      were stained with antisera against fibronectin (FN), tenascin (TN), collagen
      types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The
      composition of ECM was similar in the two groups. The expanded mesangium was
      diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained
      by type-III collagen and smooth muscle actin. Type-IV collagen was linearly
      stained along the capillary walls, imparting a double-contour feature, whereas FN
      and TN showed granular staining along the capillary walls. CD68 positive cells
      were increased in severe transplant glomerulopathy, but this increase was not
      related to ECM deposition. These findings suggest that increased glomerular
      deposition of normal and abnormal ECM components participate in the evolution of
      transplant glomerulopathy.

PMID- 10963383
TI  - Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural
      study.
AB  - The clinicopathological features of six cases of breast carcinomas showing
      features of acinic cell differentiation, which are similar to those seen in
      homologous tumors of salivary glands, are presented. The patients, all women,
      were 35-80 years of age. One case recurred after 4 years, and in two cases
      axillary lymph node metastases were found at the time of surgery. Histologically
      the tumors showed a microglandular pattern merging with solid areas.
      Cytologically, immunohistochemically, and ultrastructurally the tumors were very
      similar to cases of acinic cell carcinoma of the parotid gland. The differential
      diagnostic criteria with microglandular adenosis and carcinomas showing granular
      cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have
      to be added to the long list of tumors that affect the salivary glands and can
      also arise in the breast.

PMID- 10963384
TI  - Morphometric index of adult renal cell carcinoma. Comparison with the Fuhrman
      grading system.
AB  - Various grading systems have been proposed for renal cell carcinoma (RCC), using
      nuclear, cytoplasmic, and architectural features. The available evidence suggests
      that nuclear grading is a better prognostic indicator than other types of grading
      schemes. Nuclear morphometry may still improve the correlation of the nuclear
      grading with survival, however, because observer consistency is lacking in the
      subjective grading of RCC. The aim of this study was to investigate
      morphometrically whether RCC cases show a continuous spectrum of nuclear changes
      or whether there are discrete groups of cancer that correspond to the four
      Fuhrman grades. Karyometry was performed on 5- microm-thick, haematoxylin- and
      eosin-stained sections from 60 cases of conventional (clear cell) RCC. The
      analysis also included the evaluation of normal renal tissue (proximal tubules)
      adjacent to cancer. In each case the difference between the value of the cancer
      and the corresponding normal epithelium was calculated to represent,
      quantitatively, the degree of similarity between the tumour tissue and the
      internal normal control. When the differences were sorted into ascending order, a
      steady increase in values was observed for both the nuclear and the nucleolar
      features. A monotonic trend was evident for the differences in the mean maximum
      nuclear diameter and mean nucleolar area. When the differences between the values
      in the cancer and in the corresponding normal epithelium of these two features
      were summed up, the method resulted in a continuous variable, or nuclear
      morphometric index, related to the degree of deviation of each individual RCC
      from its internal normal control. The lowest index values were observed in of
      Fuhrman grade I cases, whereas values ranging from 2.679 to 5.422 were associated
      with cases graded II. Values equal to or higher than 5.951 were seen in the cases
      assigned to either grade III or grade IV. Partial overlap was present between the
      index values in grades III and IV. The RCC cases can be represented by a
      continuous index that corresponds to the morphological grading based on the
      Fuhrman scheme. This study shows that the index may be useful in supplementing
      the pathologist's grading. This issue can be further addressed with follow-up
      studies.

PMID- 10963385
TI  - Multifocal epithelioid angiosarcoma of the small intestine.
AB  - A 67-year-old man presented with weight loss, intermittent severe abdominal pain
      and melaena. Initial radiology (including abdominal ultrasonography), gastroscopy
      and colonoscopy did not demonstrate any lesions that could explain the
      complaints. Three weeks later, upper gastrointestinal and small-bowel barium
      studies revealed two areas in the small intestine with an abnormal mucosal
      pattern. Explorative laparotomy revealed three tumoral lesions. Three partial
      enterectomies were performed. Gross examination showed centrally depressed dark
      reddish tumoral lesions extending from the mucosa throughout the full thickness
      of the bowel wall (diameter varying between 1.6 cm and 2.2 cm). The tumours,
      composed of large, plump, polygonal cells showing little architectural
      differentiation, were mainly situated in submucosa and muscularis propria. The
      growth pattern appeared rather solid. The epithelioid cells showed pronounced
      nuclear pleomorphism and atypia with central large nucleoli. There were several
      small blood vessels with occasional anaplastic endothelial cells.
      Immunohistochemical staining demonstrated an intense expression of CD 31, CD 34,
      factor VIII related antigen and keratin. This supported the diagnosis of an
      epithelioid angiosarcoma. The patient died 3 months after diagnosis. Tumours of
      the small intestine are very rare, and angiosarcomas of the small intestine are
      even more rare. Epithelioid variants have only been described in two patients and
      only one of these had a multifocal presentation. The prognosis is very poor.
      Because of the epithelioid growth pattern and the cytokeratin expression, these
      tumours may erroneously be diagnosed as a carcinoma.

PMID- 10963387
TI  - Congenital hepatic fibrosis in 3 siblings with phosphomannose isomerase
      deficiency.
AB  - Congenital hepatic fibrosis is a rare disorder of intrahepatic bile ducts with
      the persistence of embryological bile duct structures in ductal plate
      configuration. Three siblings aged 18, 17 and 14 years old were found to have
      congenital hepatic fibrosis associated with a deficiency of the enzyme
      phosphomannose isomerase. The clinical symptoms were recurrent attacks of
      persistent vomiting with diarrhea and mild hepatomegaly. The biochemical
      abnormalities included elevated serum transferases during attacks, clotting
      factor deficiencies and persistent hypoalbuminemia. In the youngest patient
      protein-losing enteropathy was present. Liver biopsies of the three patients
      taken when they were 1, 3 and 14 years old showed an excess of bile duct
      structures in ductal plate configuration with mild fibrosis in the portal triads.
      In one patient the liver biopsy was repeated after 18 years and showed only a
      mild progression of fibrosis in the portal triads. Duodenal biopsies taken in
      infancy in two of the three patients did not show any abnormalities. Recognition
      of phosphomannose isomerase deficiency in association with congenital hepatic
      fibrosis and protein-losing enteropathy is important, because some of the
      clinical symptoms are potentially treatable by oral mannose therapy.

PMID- 10963386
TI  - A case of dermatofibrosarcoma protuberans of the vulva with a COL1A1/PDGFB fusion
      identical to a case of giant cell fibroblastoma.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a highly recurrent low-grade soft
      tissue sarcoma, which is usually located on the trunk. Presentation in the vulva
      is rare, with only 13 cases being reported to date, none of which have been
      investigated at the cytogenetic or molecular level. Specific cytogenetic
      abnormalities, involving chromosomes 17 and 22, are characteristic features of
      DFSP and giant cell fibroblastoma (GCF), a tumor closely related to DFSP. These
      chromosomal rearrangements result in the fusion of the COL1A1 and PDGFB genes in
      both lesions and show wide variation in the position of the fusion point in
      COL1A1. Here, we describe a case of DFSP of the vulva with a typical monotonous
      storiform pattern, with no foci of multinucleated giant cells. Cytogenetic
      analysis showed a 47,XX,+r karyotype in 50% of the cells, and molecular
      investigation disclosed the presence of a transcript fusing COL1A1 exon 37 to
      PDGFB exon 2. This is the first case of DFSP showing such a fusion point, which
      is intriguingly identical to that found in a GCF case, indicating that the
      COL1A1/PDGFB fusion point position does not seem to affect tumor morphology. This
      finding further underlines the very close relationship between these two
      morphologically distinct entities.

PMID- 10963388
TI  - We are carried high and raised up by their giant size.

PMID- 10963389
TI  - Angiographic characteristics of coronary artery disease in diabetic patients
      compared with matched non-diabetic subjects.
AB  - The aim of this study was to assess the extent and the severity of coronary
      artery disease (CAD) in diabetic patients. Angiographic findings were
      retrospectively analysed in 50 diabetic and in 50 non-diabetic patients, matched
      for age and sex, undergoing coronary angiography for evaluation of clinically CAD
      or silent ischaemia. Baseline characteristics did not show any increase of
      cardiovascular risk in diabetics compared to the non-diabetic group. Diabetic
      patients present less chest pain and more electric abnormalities, reflecting CAD
      specificity for diabetic patients. Angiograms of the coronary tree were divided
      into 13 segments and two experienced angiographers have developed a methodic
      analysis of selected coronary segment stenosis. The number of significant
      coronary artery stenosis (> or = 50%) per patient was higher in diabetic than in
      non-diabetic subjects (5.06+/-2.16 vs 2.40+/-1.97, p < 0.05). Diabetics had also
      more left main CAD (7/50 vs 1/50,p < 0.05). Though we did not find at any time
      statistical difference for multivessel, distal or diffuse CAD between the two
      groups, nevertheless there are more diffuse and distal lesions of the diabetic
      coronary artery trees. This debate is not closed, there is always controversy
      concerning whether the angiographic findings in diabetic or non-diabetic patients
      are different. But these results corroborate the hypothesis of a greater severity
      of angiographic proven CAD in diabetic than in non-diabetic patients, especially
      in the left main coronary artery.

PMID- 10963391
TI  - Attitudes of Italian physicians towards intensive metabolic control in Type 2
      diabetes. The QuED Study Group-Quality of Care and Outcomes in Type 2 Diabetes.
AB  - AIMS: To investigate attitudes and expectations of Italian physicians relative to
      intensive metabolic control in Type 2 diabetes (T2DM) and to compare them with
      the recent results of the UK Prospective Diabetes Study (UKPDS). METHODS: Before
      the results of the UKPDS were published, a postal questionnaire was sent to 284
      diabetologists practising in 237 outpatient diabetes clinics and 107 general
      practitioners (GPs) to explore their attitudes toward a tight metabolic control
      and target fasting blood glucose (FBG) level used. We also investigated
      clinicians' preferences for an aggressive policy in specific patient subgroups
      and their expectations about the impact of a strict metabolic control on some of
      the major end-points included in the UKPDS study. RESULTS: The questionnaire was
      filled in by 199 diabetologists and 94 GPs (response rate=75%). Although 54% of
      the respondents declared to seek a strict metabolic control, only 15% of them
      used target FBG levels < or = 110 mg/dl, while 38% pursued values > 130 mg/dl.
      GPs declared significantly less often than diabetologists to adopt an aggressive
      policy (35% vs 65%, p=0.001), and chose more often a target for FBG > 130 mg/dl
      (44% vs 36%, p=0.02). Only 62% of doctors favouring a strict metabolic control
      for the average T2DM patient would recommend it for women and 36% for subjects
      with low educational level. Diabetologists were significantly more likely than
      GPs to pursue an aggressive policy in obese subjects (70% vs 61%, p=0.03), women
      (55% vs 18%, p=0.001) and patients with other cardiovascular risk factors (92% vs
      81%, p=0.02). The vast majority of respondents did expect a positive impact of a
      tight metabolic control on micro- and macrovascular complications and on overall
      mortality. CONCLUSIONS: Italian doctors have extremely heterogeneous attitudes
      and too optimistic expectations relative to intensive metabolic control in T2DM
      patients. To facilitate the adoption of UKPDS findings, clear guidelines are
      needed, providing specific recommendations about subgroups of patients showing a
      higher risk of complications as well as of inappropriate care.

PMID- 10963390
TI  - Circulating plasma endothelin-1, plasma lipids and complications in Type 1
      diabetes mellitus.
AB  - The damage of endothelial integrity is an important step in the atherogenic
      process. To evaluate the role of circulating endothelin-1 (ET-1) in Type 1
      diabetes mellitus (T1DM), plasma ET-1 levels were evaluated in T1DM patients
      either with (n=9) or without hyperlipidaemia (n=11), or with (n=9) and without
      (n=11) late diabetic complications, in non-diabetic hyperlipidaemic patients
      (n=17) and in healthy volunteers. Groups were matched for age, sex and body mass
      index. RESULTS: Serum total cholesterol and apolipoprotein B were significantly
      higher in the diabetic group (p<0.05). Plasma ET-1 level was similar in controls
      and in non-diabetic hyperlipidaemic subjects (5.77+/-1.74 ng/l vs 4.97+/-1.58
      ng/l); however, diabetic hyperlipidaemic patients had a significantly higher
      plasma ET-1 concentration compared to control subjects (6.67+/-2.44 ng/l vs
      4.97+/-1.58 ng/l, p<0.05). Diabetic patients with vascular complications had a
      significantly higher plasma ET-1 concentration than found in diabetic patients
      without complications (6.99+/-2.17 ng/l vs 4.74+/-1.27 ng/l, p<0.01) and in
      controls (6.99+/-2.17 ng/l vs 4.97+/ 1.58 ng/l, p<0.01). Patients with diabetic
      complications also had a significantly higher apolipoprotein B level compared to
      healthy controls (0.94+/-0.37 g/l vs 0.66+/-0.12 g/l, p<0.005). CONCLUSION: The
      susceptibility of T1DM patients to the development of atherosclerosis might be
      attributed to the relationship between elevated lipid levels and ET-1.

PMID- 10963392
TI  - Health-related quality of life in obesity: the role of eating behaviour.
AB  - A poor health-related quality of life (HRQL) has been repeatedly documented in
      obesity. Overweight per se and associated diseases affect physical fitness,
      whereas mental well-being depends on social, cultural and behavioural components.
      Very few studies are available on HRQL in obese persons in relation to eating
      behaviour. We measured HRQL by means of Short-Form-36 questionnaire in 183 obese
      subjects, seeking specific treatment at a University-based weight management
      center. Only half had a Body Mass Index exceeding 35 kg/m2. Data were compared to
      age- and gender-adjusted normative values of the Italian population (2031
      subjects). The Binge Eating Scale (BES) and the Three-Factor Eating Questionnaire
      (TFEQ) were used to assess eating behaviour. Most domains of HRQL were impaired
      in obese subjects, more severely in younger subjects and in females. The severity
      of overweight progressively affected physical fitness, but had a minor effect on
      mental status. In over 50% of subjects, BES and TFEQ identified a binge eating
      pattern, more frequently in females. A positive BES, as well as lower
      restriction, higher disinhibition and hunger values at TFEQ, identified subjects
      with poorer HRQL. Logistic regression analysis identified in a positive BES the
      variable more closely associated with low scores in mental domains of perceived
      HRQL. Waist-to-hip ratio, degree of obesity, osteoarticular and respiratory
      diseases, but also positive BES, were selected as variables more closely
      associated with poor physical fitness. HRQL is variably impaired in obese persons
      seeking treatment for their disease, mainly in patients with binge eating.
      Treatment of binge eating may be as important as any weight-reducing intervention
      for the overall well-being of the majority of obese persons.

PMID- 10963393
TI  - Impairment of the respiratory system in diabetic autonomic neuropathy.
AB  - Diabetic autonomic neuropathy (DAN) may affect up to 30% of the diabetic
      population. Sometimes DAN becomes clinically manifest causing specific symptoms
      and signs; more often, however, DAN is responsible for subtle alterations
      detectable only by functional tests, as in the case of the respiratory system. At
      first, abnormalities both in the bronchomotor tone and aspecific airway
      responsiveness to different stimuli were recognised in diabetic patients with
      DAN, indicating a defective control of mechanisms which regulate the bronchial
      calibre in these subjects. Subsequently, peculiar changes in breathing pattern
      and greater ventilatory requirements have been observed during incremental
      exercise in diabetics with DAN, suggesting an altered control of breathing in
      stressful conditions. Alterations in either peripheral or central
      chemosensitivity have been repeatedly shown in these patients, with marked
      differences related to the severity of DAN, concerning the neuro-muscular and
      ventilatory responsiveness to CO2. Following anecdotal reports, respiratory
      disturbances during sleep have been more carefully investigated in diabetic
      subjects and greater prevalence of sleep apnea, mainly in the obstructive form,
      has been found in the presence of DAN. The underlying mechanisms of sleep
      disordered breathing, however, are poorly understood in DAN and further studies
      are needed to elucidate them.

PMID- 10963394
TI  - Use of insulin lispro in pregnancy.

PMID- 10963395
TI  - The Croatian model of diabetes care and the St. Vincent Declaration.

PMID- 10963396
TI  - Hepatopancreatic alterations in Litopenaeus vannamei (Boone, 1939) (Crustacea:
      Decapoda: Penaeidae) experimentally infected with a Vibrio alginolyticus strain.
AB  - As in other countries, the presence of disease has affected and limited the
      development of shrimp culture in Venezuela. Vibriosis is one of the most
      prevalent, causing high mortality not only in larval cultures but also in shrimp
      production. The present work shows the histological changes in hepatopancreas of
      Litopenaeus vannamei experimentally induced by a strain of Vibrio alginolyticus.
      The shrimps were infected by the immersion technique, being exposed to a
      concentration of 5.2 x 10(7) bacteria/ml. As soon as their behavior indicated a
      moribund condition, the animals were sacrificed, and their hepatopancreata were
      fixed and processed for histological observation. Light microscopical
      observations revealed loss of the acinar structure of the digestive gland and
      sloughing off of cellular lining because of cytolisis. The acinar cellular
      content was dispersed within the lumina and among the acini. Clusters of
      hemocytes, in the majority loaded with bacteria, were observed under the
      connective tissue capsule surrounding the hepatopancreatic lobes and in the hemal
      spaces of the connective tissue sheath surrounding the tubules.

PMID- 10963397
TI  - Further characterization of the gonad-specific virus of corn earworm, Helicoverpa
      zea.
AB  - The gonad-specific virus (GSV) is a DNA virus infecting the reproductive tracts
      of adults of both sexes of the corn earworm, Helicoverpa zea, causing severe
      tissue deformities leading to sterility. Atypical occlusion bodies containing
      large concentrations of virions embedded in a granular matrix were seen in the
      lumen of the oviduct and the bursa copulatrix of infected females. The virus,
      transmitted by both sexes, was successfully propagated in vivo and in tissue
      culture. The GSV genome is about 225 kb in size, with no apparent similarity to
      the nucleopolyhedrovirus type species, AcMNPV, genomic DNA, as determined by
      Southern hybridization. PCR amplification of GSV genomic DNA with primers derived
      from the highly conserved polyhedra gene of several baculoviruses indicated no
      similarity. GSV at 10(-2) female equivalents (based on virus obtained from the
      bursa copulatrix and oviducts of one infected female) injected into a newly
      emerged female and mated to a normal male resulted in >95% agonadal progeny.
      However, at lower doses, some of the adult progeny looked normal but apparently
      carried a low level of the virus that could be responsible for sustenance of
      infection in a given colony, as well as in nature.

PMID- 10963398
TI  - Abnormal formation of polyhedra resulting from a single mutation in the
      polyhedrin gene of Autographa californica multicapsid nucleopolyhedrovirus.
AB  - A spontaneous mutant that produces a single abnormally large cubic polyhedron per
      infected cell was isolated from a polyhedra-positive recombinant Autographa
      californica multicapsid nucleopolyhedrovirus (AcMNPV). Both wild-type and mutant
      virus produce two forms of virus particles, budded virions and occluded virions.
      However, occluded virions are not found within the polyhedra of cells infected
      with mutant virus, as with the wild-type virus. These large cubic polyhedra do
      not have the typical lattice-like structure normally seen in wild-type polyhedra
      and are noninfectious. Spodoptera frugiperda 9 (SF9) cells which were infected
      with this virus had low infectivity to larvae. No significant alterations were
      found in the viral genome by restriction enzyme analysis, and no mutations were
      found in the 25K gene. A single point mutation resulting in an amino acid change
      of Gly25 to Asp was identified in the polyhedrin gene. A transfer vector
      containing the entire polyhedrin gene including the point mutation was
      constructed and used to cotransfect Sf9 cells with a polyhedron-negative
      recombinant virus. Large cubic polyhedra were once again observed, confirming
      that the Gly25 to Asp mutation is responsible for the formation of abnormal
      polyhedra.

PMID- 10963399
TI  - Dynamics of Wolbachia populations in transfected lines of Trichogramma.
AB  - Fluorescence in situ hybridization was tested to specifically detect symbionts of
      the genus Wolbachia in Trichogramma and to allow for semiquantitative estimations
      of symbiont abundance. Extraction solutions used for horizontal transfers of
      symbionts contain a high abundance of Wolbachia, but Wolbachia have a low and
      decreasing abundance in microinjected lines (transfected lines). Moreover, eggs
      of microinjected lines were shown to be polymorphic for the infection. In
      naturally infected lines, Wolbachia are localized at the posterior pole of the
      eggs; they are scattered during the early stages of larval development and then
      concentrated in the ovaries at the end of the female pupal development.
      Scattering and concentration are probably not active but rather the result of
      replications or morphogenesis. Conversely, Wolbachia are not concentrated at the
      posterior pole of eggs in microinjected lines. Comparison of the within-family
      and between-family variances of the symbiont abundance in a microinjected line
      did not lead us to conclude that this character shows a genetic variability.

PMID- 10963400
TI  - Detection of Bonamia ostreae based on small subunit ribosomal probe.
AB  - Bonamia ostreae is a protozoan parasite of the flat oyster, Ostrea edulis, which
      has caused significant loss of oysters in Europe over the last decade. B. ostreae
      was purified from infected flat oysters and DNA was extracted. The nearly
      complete small subunit rDNA gene of B. ostreae was amplified using universal
      oligonucleotides and the PCR product was cloned and sequenced. BLAST research
      with this sequence revealed similarities to Haplosporidium nelsoni,
      Haplosporidium costale, and Minchinia teredinis. These data suggest that B.
      ostreae may be included in the genus Haplosporidium. Specific B. ostreae primers
      were designed for labeling, by PCR, a probe. This probe was successfully used by
      in situ hybridization to detect B. ostreae in infected fiat oysters, thus
      confirming the accuracy of this SSU rDNA sequence. The probe lead also to the
      detection of Bonamia sp. in infected Tiostrea chilensis and H. nelsoni in
      infected Crassostrea virginica but not Mikrocytos mackini infected Crassostrea
      gigas. These primers were also used to detect B. ostreae from infected oyster
      tissues by PCR. This B. ostreae SSU rDNA gene sequence provides genetic
      information as a first step toward elucidation of the taxonomic boundaries among
      the microcell organisms. Moreover, the development of DNA detection assays will
      be valuable specific diagnostic tools.

PMID- 10963401
TI  - Venom from the endoparasitic wasp Pimpla hypochondriaca adversely affects the
      morphology, viability, and immune function of hemocytes from larvae of the tomato
      moth, Lacanobia oleracea.
AB  - During oviposition, the endoparasitic wasp Pimpla hypochondriaca injects its
      pupal hosts with venom. This complex fluid has toxic properties and recently
      several venom components were characterized. In addition, it was suggested that
      venom might be involved in host immune suppression. For this to be the case,
      venom would have to adversely affect hemocytes and this aspect was further
      addressed in the current study utilizing the larval stage of the tomato moth
      Lacanobia oleracea as a model system. Using sublethal venom injections we
      investigated the effects of venom on encapsulation and hemocyte concentration.
      Additionally, the effects of venom on hemocyte morphology, viability, and
      phagocytic capability were determined in vitro. Injection of 16 microg of venom
      protein into sixth instar larvae was sufficient to reduce the ability of
      hemocytes to encapsulate Sephadex A25 beads by more than 50% in four of five
      insects examined. Hemocyte concentration in sixth instar larvae 32 h after
      injection with 16 microg of venom was reduced by 56% compared to that in
      controls. Damaged hemocytes and cell debris were also observed in hemolymph from
      venom-treated insects, suggesting that P. hypochondriaca venom has cytotoxic
      properties. In vitro incubation of washed hemocytes for 20 h with 500 ng/microl
      venom resulted in disintegration of a high proportion of hemocytes, leaving only
      parts of the plasma membrane and nucleus intact. Treatment with low
      concentrations of venom (1.6 ng/microl) resulted in an absence of spread
      plasmatocytes, which were abundant on control monolayers. High-resolution
      microscopy of hemocyte cultures exposed to 320 ng/microl venom for 3.5 h on glass
      slides indicated that venom induced a variety of effects on cellular morphology,
      including blebbing of the plasma membrane, degranulation, and the formation of
      cytoplasmic vacuoles. Incubation of hemocytes with 320, 64, or 3.2 ng/microl
      venom for 3.5 h reduced cell viability to 70, 90, and 92%, respectively,
      confirming that venom is cytotoxic to hemocytes. Treatment with 320 ng/microl
      venom reduced the capacity of hemocytes to phagocytose Escherichia coli by 85%.
      Together, these results demonstrate that at sublethal doses venom has a potent
      anti-hemocyte action and can impair hemocyte-mediated immune responses.

PMID- 10963402
TI  - Nitrogen partitioning in Heterorhabditis bacteriophora-infected hosts and the
      effects of nitrogen on attraction/repulsion.
AB  - Entomopathogenic nematode behavior is affected by the condition of their infected
      hosts. We hypothesized that nitrogen compounds released from infected hosts may
      be one factor affecting entomopathogenic nematode host-finding and infection
      behaviors. Our objectives were to (1) investigate the partitioning of nitrogen in
      Galleria mellonella (L.) infected by Heterorhabditis bacteriophora Poinar and (2)
      determine attraction and repulsion of H. bacteriophora to various quantities of
      nitrogen (ammonia). Volatile (ammonia), organic, and inorganic nitrogen forms
      were monitored during the course of infection. Approximately 0.052 mg of nitrogen
      was released from a single infected host as volatile ammonia. Most of the ammonia
      release was detected within the first 3 days postinoculation. Organic nitrogen
      increased during the course of infection, whereas inorganic nitrogen decreased.
      The net nitrogen change in the infected host consisted of a loss of approximately
      47 mg, most of which was lost within the 1st week of infection. Accelerated loss
      of nitrogen early in the infection process was likely correlated with activity
      and growth of bacterial symbionts. Increased organic nitrogen was likely
      associated with nematode reproduction within the host. Attraction or repulsion of
      H. bacteriophora to nitrogen (ammonium hydroxide) was measured on agar quadrant
      plates. Nematodes were attracted to 16 and 160 microg of nitrogen and repelled by
      concentrations of 1600 and 8000 microg. Our data indicate that nitrogen released
      from H. bacteriophora-infected hosts attracts nematodes at lower levels (early in
      the infection) and repels them at higher concentrations (later in the infection
      process).

PMID- 10963403
TI  - Comparison of the soluble organic matrices of healthy and diseased shells of
      Pinctada margaritifera (L.) and Pecten maximus L. (Mollusca, Bivalvia).
AB  - Pinctada margaritifera and Pecten maximus are among the mollusks of commercial
      value. Both are known to show abnormal calcification processes that strongly
      increase the mortality rate. Several parameters of the soluble organic matrices
      extracted from the shells of P. margaritifera and P. maximus are analyzed: bulk
      composition, molecular weights, and acidity. The composition of the matrices of
      healthy and diseased shells were compared, showing that the protein and the sugar
      contents are variously modified. Differences between healthy and diseased shells
      are dissimilar in the two species. This is in accordance with the previously
      described macroscopic and microscopic alterations (red color, numerous brown
      membranes). This study does not allow identification the origin of the disease,
      but provides new insights on the role of sugars in biomineralization processes.

PMID- 10963404
TI  - Activation pattern and toxicity of the Cry11Bb1 toxin of Bacillus thuringiensis
      subsp. medellin.
AB  - Bacillus thuringiensis protoxins undergo proteolytic processing in the midgut of
      susceptible insects to become active. The ability to process the Cry11Bb1
      protoxin by trypsin and Culex quinquefasciatus larval gut extracts was tested.
      The protease activity indicated by the appearance of proteolytic products
      increased with an increment in pH, with the highest activity being observed at pH
      10.6. A time course study showed the proteolysis of the 94-kDa Cry11Bb protein
      ending with the production of fragments of relative molecular mass of 30 and 35
      kDa within 5 min. In vitro, gut proteases extract cleaved the solubilized toxin
      between Ser59 and Ile60 and between Ala395 and Asn396, generating a 30-kDa N
      terminal and a 35-kDa C-terminal fragment, respectively. Similarly, mosquito
      larvae processed in vivo the parasporal inclusions, generating the same fragments
      as those observed in vitro. The Cry11Bb1 protoxin activated with trypsin or gut
      proteases showed larvicidal activity against C. quinquefasciatus first instar
      larvae. The data suggest that gut proteases participate in the activation of
      CryllBbl protoxin, generating at least two different fragments on which the
      activity could reside.

PMID- 10963405
TI  - Alterations in hemolymph and extrapallial fluid parameters in the Manila clam,
      Ruditapes philippinarum, challenged with the pathogen Vibrio tapetis.
AB  - In a recent study, we demonstrated the presence of defense factors, competent
      hemocytes and high enzymatic activities (peptidases, hydrolases, lytic, etc.), in
      the extrapallial fluid, located between the mantle and the shell, of the Manila
      clam, Ruditapes philippinarum. In Europe, this species is affected by brown ring
      disease, an epizootic disease caused by the bacterium Vibrio tapetis. The present
      work focused on the effect of the development of the disease on cellular and
      humoral defense parameters in the hemolymph and the extrapallial fluid of
      experimentally infected clams. Results indicate significant changes in total and
      dead hemocyte counts, as well as modifications in lysozyme activity and protein
      content, in the hemolymph and extrapallial fluid of challenged animals. Hemocyte
      counts and lysozyme activity increased significantly in the hemolymph, but
      particularly in the extrapallial fluid, where the highest values were observed. A
      healing (recalcification) process was observed 7 weeks following challenge,
      suggesting defense system efficiency at neutralizing the pathogen. These results
      are discussed with emphasis on the role of extrapallial fluids in the defense
      process against invading microorganisms.

PMID- 10963406
TI  - Screening for Bacillus thuringiensis crystal proteins active against the cabbage
      looper, Trichoplusia ni.
AB  - Toxicity tests were performed to find among Cry1 and Cry2 Bacillus thuringiensis
      crystal proteins those with high activity against the cabbage looper. Tests were
      performed with neonate larvae on surface-contaminated artificial diet. The
      crystal proteins found to be toxic were, from higher to lower toxicity: Cry1Ac,
      Cry1Ab, Cry1C, Cry2Aa, Cry1J, and Cry1F (LC50 of 1.14.1, 3.4-4.4, 12, 34, 87, and
      250 ng/cm2, respectively). Cry1B, Cry1D, and Cry1E can be considered nontoxic
      (LC50 higher than 2500 ng/cm2). Cry1Aa was moderately toxic to nontoxic,
      depending on the source (LC50 of 420 ng/cm2 from PGS and 8100 ng/cm2 from
      Ecogen). In vitro binding assays with trypsin-activated 125I-labeled Cry1Aa,
      Cry1Ab, and Cry1Ac crystal proteins and brush border membrane vesicles from
      midgut larvae showed a direct correlation between toxicity and binding affinity.
      Heterologous competition experiments indicated that Cry1Aa and Cry1F bind, though
      only at very high concentrations, to the Cry1Ab/Cry1Ac shared high-affinity
      binding site.

PMID- 10963407
TI  - Laboratory tests of the susceptibility of some forest insect pests to
      Heterorhabditis megidis H90 (Nematoda).

PMID- 10963408
TI  - Two collagenases are secreted by teratocytes from Microplitis mediator
      (Hymenoptera: Braconidae) cultured in vitro.

PMID- 10963409
TI  - Cross-resistance to Bacillus thuringiensis toxin Cry1Ja in a strain of
      diamondback moth adapted to artificial diet.

PMID- 10963410
TI  - Occupational health in Argentina.
AB  - Argentina is within the denominated "new industrialised countries", with the
      characteristic of having high contrasts in the urban population, based on service
      and industry, and in the rural population, based on agriculture and cattle, still
      the main sources of wealth in the country. The process of globalisation and the
      need to compete hard in international markets have provoked high unemployment and
      the transfer of workers from a formal market to an informal one. Legislation on
      occupational health is old and it is in the process of being updated. The system
      of prevention, assistance and compensation for accidents at work and for
      occupational illnesses has changed from being optative for employers, to the
      compulsory hiring of private insurance companies. The Government keeps the role
      of supervisor of the system. There are enough professionals in occupational
      health, hygiene and safety but not occupational nurses. The teaching is given by
      many universities and professional associations, some of which have an active
      profile in the occupational health of the country.

PMID- 10963411
TI  - Whole-body vibration and low back pain: a systematic, critical review of the
      epidemiological literature 1992-1999.
AB  - OBJECTIVES: A previous extensive review of the literature including that from the
      middle of 1992 concluded that whole-body vibrations may contribute to low back
      pain, but that the exposure-response relationship had not been clarified. We
      reviewed the literature of the past 7 years to find out: (i) whether there is
      evidence in the recent epidemiological literature for a causal association
      between whole-body vibrations and low back pain, and (ii) if there is evidence in
      the recent literature for a dose-response relationship between whole-body
      vibrations and low back pain. METHODS: All relevant epidemiological articles
      which were obtained through a search in the databases MEDLINE, OSH-ROM and
      TOXLINE, and through personal communication, were reviewed independently by the
      two authors, using a checklist. RESULTS: Twenty-four original articles concerning
      the association between whole-body vibrations and the lower back were retained
      for use. The quality of the papers was mostly low, but improved with time. Only
      seven articles passed our predetermined quality criteria. Of the seven reports,
      one showed increased frequency of lumbar prolapse in occupational drivers, and
      six showed low back pain to be more frequent in whole-body vibration-exposed
      groups. Only two out of the four articles reporting on dose, showed a dose
      response association. CONCLUSIONS: Despite the lack of definite evidence, we
      found sufficient reasons for the reduction of whole-body vibration-exposure to
      the lowest possible level. If new knowledge is to be produced, good prospective
      studies with repeated measurements of exposure, analyses of work postures, and
      clear definitions and subgroupings of low back pain are needed. Other research in
      this field should be given up, and the resources used for more important issues,
      as the size of the problem of whole body vibration is probably on the decrease
      because of the technical prophylactic developments that are already in progress.

PMID- 10963412
TI  - A comparison of different lead biomarkers in their associations with lead-related
      symptoms.
AB  - OBJECTIVES: To evaluate whether dimercaptosuccinic acid (DMSA) -chelatable lead,
      an estimate of current bioavailable lead stores, is a better predictor of lead
      related symptoms than are other commonly used lead biomarkers. METHODS: A total
      of 95 male lead workers from three lead industries (one secondary lead smelting
      facility, one polyvinyl chloridestabilizer manufacturing plant, and one lead-acid
      storage battery factory), and 13 workers without occupational lead exposure
      recruited from an occupational health institute, were studied. Blood lead, blood
      zinc protoporphyrin (ZPP), 4 h DMSA-chelatable lead (after oral administration of
      10 mg/kg DMSA), urine lead, and urinary delta-aminolevulinic acid levels were
      evaluated as predictors of 15 lead-related symptoms, assessed by self
      administered questionnaire, with linear and logistic regression controlling for
      covariates. Total symptoms and symptoms in three categories (gastrointestinal,
      neuromuscular, and general) were evaluated. RESULTS: The mean (SD) 4 h DMSA
      chelatable lead level was 288.7 (167.7) microg, with a range from 32.4 to 789
      microg in the 95 lead workers. The mean (SD) in the non-exposed subjects was 23.7
      (11.5) microg with a range from 10.5 to 43.5 microg. Blood lead, blood ZPP, and
      spot urine lead levels ranged from 21.4 to 78.4 microg/dl, 40 to 331 microg/l,
      and 7.5 to 153.0 micro/l, respectively, in the lead workers, and from 4.0 to 7.2
      micro/dl, 27 to 52 microg/l, and 2.9 to 15.5 microg/l in the non-exposed
      controls, respectively. The overall mean symptom score (SD), derived as the sum
      of 0 or 1 point for absence or presence of 15 symptoms, of the lead workers was
      3.7 (2.0), compared to 1.2 (1.5) for the non-exposed workers. DMSA-chelatable
      lead was the best predictor of symptom scores in both crude and adjusted
      analyses, compared with the other biomarkers. Lead workers with DMSA-chelatable
      lead values greater than the median (260.5 microg) were 6.2 times more likely to
      have frequent tingling or numbness of the arms or legs and 3.3 times more likely
      to have muscle pain than subjects with lower chelatable lead values. Three
      symptoms (tingling or numbness of arm or leg, muscle pain, and feeling irritation
      at the slightest disturbance) evidenced a dose-dependent relationship with DMSA
      chelatable lead levels. CONCLUSIONS: DMSA-chelatable lead was found to be the
      best predictor of lead-related symptoms, particularly of both total symptom
      scores and neuromuscular symptoms, than were the other other lead biomarkers.

PMID- 10963413
TI  - 8-Hydroxydeoxyguanosine in leukocyte DNA and urine of quartz-exposed workers and
      patients with silicosis.
AB  - OBJECTIVE: To examine radical-induced DNA damage and its elimination in workers
      exposed to quartz and in patients with silicosis, and to assess the relationship
      of these effects to lung function. METHODS: Blood and spontaneous urine samples
      were obtained from active, quartz-exposed workers without silicosis (n = 63), and
      from retired workers with silicosis (n = 42). Levels of 8-hydroxydeoxyguanosine
      (8-OHdG) were determined in peripheral blood leukocyte DNA and urine, by the use
      of high-performance liquid chromatography coupled with ultra violet- (UV) and
      electrochemical detection. RESULTS: No significant differences in the mean levels
      of 8-OHdG in leukocyte DNA and of urinary excretion of 8-OHdG were found between
      silicosis patients and quartz-exposed healthy workers. However, in the group of
      silicosis patients with increased oxidative DNA damage the urinary excretion of 8
      OHdG was lower than in the corresponding group of active workers without
      silicosis. In the case of silicosis, urinary 8-OHdG correlated positively, and 8
      OHdG in DNA correlated negatively, with forced expiratory volume in one second
      (FEV1) and forced vital capacity (FVC). Healthy workers with a personally
      estimated high dust exposure in the workplace showed higher levels of 8-OHdG in
      DNA than did workers with moderate dust exposure. No association of 8-OHdG
      formation and/or elimination with duration of employment, field of activity,
      smoking or age was found. CONCLUSION: Our findings suggest that a less effective
      repair of 8-OHdG is associated with a higher degree of pulmonary airway
      obstruction in patients with silicosis.

PMID- 10963414
TI  - Propylene glycol monomethyl ether (PGME) occupational exposure. 1. Biomonitoring
      by analysis of PGME in urine.
AB  - An analytical method was developed for the determination of free and conjugated
      PGME-alpha in urine. The method involves a solid-phase extraction on LC-18
      columns and a GC/FID analysis after derivatization with trimethysilylimidazole.
      The assay was linear (least-squares regression coefficient 0.996), specific,
      reproducible (intraassay variability 10%, interassay variability 10%), and
      allowed a high level of PGME recovery (more than 90%). The assay was applied to
      the analysis of urine samples from three workers who were occupationally exposed
      to PGME to estimate their exposure. The highest value of PGME concentration in
      urine was 7.78 mg/l. Air concentrations of PGME ranged between 20 and 40 ppm. A
      statistically significant correlation was found between measurements of external
      exposure and PGME in urine. An important fraction of PGME in urine was found to
      be conjugated.

PMID- 10963415
TI  - Can a battery of functional and sensory tests corrobrate the sensorineural
      complaints of subjects working with vibrating tools?
AB  - OBJECTIVES: The objective of the present paper is to study the relationship
      between the early sensorineural symptoms, classified according to the Stockholm
      scale, and the results of the main functional and sensory tests described in the
      literature, in subjects working with vibrating tools. METHODS: Three groups of
      male workers were selected from industry: one group (69 subjects) exposed to hand
      arm vibration in several workplaces, one group (62) performing heavy and
      repetitive hand and arm work but without exposure to vibration, and one control
      group (46) performing light and non-repetitive tasks without vibration. All the
      workers were interviewed by questionnaire, about their personal characteristics,
      their health status, their actual and past working conditions and the episodes of
      tingling at the level of the fingers. From these reported symptoms, the
      sensorineural stage of the hand-arm vibration was determined using the Stockholm
      scale. Based on the review of the literature, we selected six functional and
      sensory tests: maximum voluntary grip force, maximum angles of the wrist,
      pressure perception threshold test, vibration perception threshold test, distal
      sensory latency and the Purdue Pegboard test. Each test was performed by the
      workers in the three groups. RESULTS: No main differences were observed between
      the personal characteristics of the three groups. According to the Stockholm
      scale, the sensorineural symptoms were mainly at stage SN1, with 9% at stage SN2
      and none at stage SN3. These symptoms are associated with exposure to vibration,
      and had a prevalence of 40% in group 1, versus 20% in the two other groups.
      Furthermore, 25% of the workers exposed to vibration complained of symptoms at
      least once a week, compared with only 2% in the other groups. The multivariate
      logistic regression analysis showed an association between the existence of
      symptoms and a decrease in the maximum flexion angle of the wrist and an increase
      in the pressure perception threshold. This association, however, was too low to
      determine limit values with a sensitivity and specificity sufficiently high to
      make a reliable diagnosis. CONCLUSIONS: The sensorineural symptoms at stage N1 on
      the Stockholm scale, experienced occasionally by some 40% of the users of
      vibrating tools, could not be corroborated by the functional and sensory tests.

PMID- 10963416
TI  - A mortality study among workers in a French aluminium reduction plant.
AB  - OBJECTIVE: A mortality study on the association between lung cancer and
      occupational exposure to polycyclic aromatic hydrocarbons (PAHs) was carried out
      in a French aluminium reduction plant. This study updated a previous mortality
      study. METHOD: The historical cohort included every male worker who had been
      employed in the plant for at least 1 year between 1950 and 1994. Workers were
      followed-up for mortality from 1968 to 1994. Causes of death were obtained from
      death certificates. Standardised mortality ratios (SMRs) and 95% confidence
      intervals (CI) were computed using regional mortality rates as external reference
      to compare observed and expected numbers of deaths, adjusted for gender, age and
      calendar time. RESULTS: The cohort comprised 2,133 men, of whom 335 died during
      the follow-up period. The observed mortality was lower than expected for all
      causes of death (SMR = 0.81, CI 0.72-0.90) and for lung cancer (observed = 19,
      SMR = 0.63, CI 0.38 0.98). No lung cancer excess was observed in workshops where
      PAH exposure was likely to have occurred, and no trend was observed according to
      duration of exposure and time since first exposure. This low lung cancer
      mortality could be partly explained by a marked healthy worker effect and a
      possible negative confounding by smoking. An excess was observed for bladder
      cancer (observed = 7, SMR = 1.77, CI 0.713.64) in the whole cohort, that was
      higher among workers employed in workshops where PAH exposure was likely to have
      occurred (observed = 6, SMR = 2.15, CI 0.79-4.68). In addition, an SMR higher
      than unity was observed for "psychoses and neuro-degenerative diseases" (observed
      = 6, SMR = 2.39, CI 0.88-5.21), that could not be related to occupational
      aluminium exposure. CONCLUSION: No lung cancer risk was detected. Non-significant
      excesses were observed for bladder cancer and for psychoses and neuro
      degenerative diseases.

PMID- 10963417
TI  - Indoor exposure to polycyclic aromatic hydrocarbons and carbon monoxide in
      traditional houses in Burundi.
AB  - OBJECTIVES: Wood combustion is used as a major energy source in African countries
      and could result in indoor, pollution-related health problems. This exploratory
      study was undertaken to estimate polycyclic aromatic hydrocarbon (PAH) and carbon
      monoxide exposure in individuals living in traditional rural houses in Burundi.
      METHODS: Standard methods were used to determine indoor air concentrations of 12
      PAHs, and carbon monoxide. The urinary excretion of 1-hydroxypyrene (1-OHP) was
      measured in occupants of traditional houses, and compared with that of
      individuals living in the town of Bujumbura, the capital of Burundi. RESULTS:
      Mean airborne concentration of four volatile PAHs, naphthalene, fluorene,
      phenanthrene and acenaphthene, exceeded 1 microg/m3, and that of benzo(a)pyrene
      was 0.07 microg/m3. Naphthalene was by far the main PAH contaminant, with a mean
      concentration (+/- standard deviation) of 28.7+/-23.4 microg/m3, representing on
      average 60-70% of total PAH concentration. Carbon monoxide mean concentration (+/
      standard deviation) was 42+/-31 mg/m3, and correlated with total PAH
      concentration. Geometric mean urinary 1-OHP excretion (range) in people living in
      traditional houses was 1.50 (0.26-15.62) micromol/mol creatinine, a value which
      is on average 30 times higher than that of people living in the capital (0.05
      (0.009-0.17) micromol/mol creatinine). CONCLUSIONS: It appears that the
      substantially high concentrations of the studied contaminants constitute a
      potential health hazard to the rural population of Burundi.

PMID- 10963418
TI  - Return to work after sickness absence due to back disorders--a systematic review
      on intervention strategies.
AB  - OBJECTIVES: The aim was to review the literature with regard to the effectiveness
      of intervention programmes for the prevention of aggravation of back disorders or
      prolonged duration of sickness absence. METHODS: A systematic search of the
      literature was performed using three groups of key words and inclusion/exclusion
      criteria. Effectiveness was evaluated using two measures: the difference between
      intervention and referent groups in return to work, and the fraction of sickness
      absence among referent groups that could be prevented if these referents had
      undergone the same intervention (preventable fraction). RESULTS: Twelve articles
      with quantitative information on the effect of ergonomic interventions on return
      to work were included. In eight studies, introduction of a back-school programme
      was the preferred intervention, combining exercise and functional conditioning,
      and training in working methods and lifting techniques. In seven out of eight
      back-school studies, return to work was significantly better in the intervention
      group. Intervention after 60 days, in the subacute phase of back pain, showed the
      most promising results. In these studies the preventable fraction varied between 
      11% and 80%, largely depending on the stage and phase of back disorders and the
      time of follow-up. The success of intervention also depended on the profile of
      the referents when left untampered. In all studies compliance during the
      intervention was fairly good, but there was a lack of information on
      sustainability of the intervention during the follow-up and on recurrence of back
      complaints and consequent sickness absence. CONCLUSIONS: Few studies were
      performed to assess the outcome return to work after ergonomic intervention.
      However, there is evidence that intervention in the subacute phase of back pain
      is preferable. Future intervention studies should address intervention
      sustainability and recurrence of sickness absence due to back pain over at least
      a 1-year follow-up period.

PMID- 10963419
TI  - Propylene glycol monomethyl ether (PGME) exposure. 2. Identification of products
      containing PGME, their importance and their use in Switzerland.
AB  - OBJECTIVE: In order to identify users of PGME and potential exposures, a chemical
      registration database maintained in Switzerland was analysed. METHOD: The
      database contains information on the composition of products (qualitative and
      quantitative), the field of use, the year of registration and the domain of
      commercial applications (public or professional). RESULTS: Identification of
      potential exposures in Switzerland was carried out. Out of a total of 150,000
      products, 2334 were found to contain PGME and most contained between 1% and 10%
      PGME. There was a great increase in the number of products declared between 1983
      and 1991. The principal fields of use were in inks, varnishes and paints.

PMID- 10963420
TI  - Analysis of Japanese occupational health services for small-scale enterprises, in
      comparison with the recommendations of the Joint WHO/ILO Task Group.
AB  - OBJECTIVES: To evaluate Japanese occupational health services (OHSs) for small
      scale enterprises (SSEs). METHODS: The current Japanese OHSs for SSEs were
      compared with 15 recommendations of the Joint WHO/ILO Task Group. The status of
      OHSs was analyzed using the published papers collected by means of a computerized
      literature search. Thirty-five papers were used in the analysis, which was first
      conducted by the four authors separately, followed by discussion among the
      authors. Evaluation was conducted by classifying the status of Japanese OHSs for
      SSEs into three classes (A: good, B: average, C: poor) based on comparison with
      each recommendation. RESULTS: Six issues were evaluated as "A": establishment of
      a national policy for the provision of OHSs for SSEs, occupational health and
      safety inspection for SSEs, legislation to ensure services for SSEs and provision
      of financial incentives, adoption of occupational health programs using multiple
      channels, training in occupational health issues, and establishment of national
      data collection and registration systems. Nine issues were evaluated as "B":
      provision of OHSs for all SSEs as a part of the "national Health for ALL"
      strategy, intervention combining economic development and OHSs, extension of OHSs
      to vulnerable groups, coverage of migrant and seasonal workers by OHSs, the
      establishment of a national collaborative and coordinative body on OHSs, control
      of transfer of hazardous technology, encouragement of applied research,
      employers' commitment and worker participation, and integration of OHSs with
      primary health care. None of them was evaluated as "C". CONCLUSIONS: Japanese
      OHSs for SSEs were fairly well established in terms of compliance with the
      recommendations of the Joint WHO/ILO Task Group, although evaluation may be
      somewhat subjective and rather qualitative.

PMID- 10963421
TI  - MR imaging of articular cartilage.
AB  - With the advent of new treatments for articular cartilage disorders, accurate
      noninvasive assessment of articular cartilage, particularly with MR imaging, has
      become important. Understanding the MR imaging features of articular cartilage
      has led to the development of two types of routinely available MR imaging
      techniques which have demonstrated clinical accuracy and interobserver
      reliability.

PMID- 10963422
TI  - Chronic post-traumatic osteomyelitis of the lower extremity: comparison of
      magnetic resonance imaging and combined bone scintigraphy/immunoscintigraphy with
      radiolabelled monoclonal antigranulocyte antibodies.
AB  - OBJECTIVE: A retrospective study of the validity of combined bone scintigraphy
      (BS) and immunoscintigraphy (IS) using (99m)Tc-labelled murine antigranulocyte
      antibodies (MAB) and magnetic resonance imaging (MRI) in chronic posttraumatic
      osteomyelitis. DESIGN AND PATIENTS: The results of MRI and combined BS/IS of 19
      lesions in 18 patients (13 men, 5 women; mean age 45 years, range 27-65 years)
      were independently evaluated by two radiologists and one nuclear medicine
      physician with regard to bone infection activity and extent. The patient group
      was a highly selective collection of clinical cases: the average number of
      operations conducted because of relapsing infection was eight (range 2-27), the
      average time interval between the last surgical intervention and the present
      study was 6.5 years (range 3 months to 39 years), and from the first operation
      was 14 years (range 1.5-42 years). Interobserver agreement on MRI was measured by
      kappa statistics. Sensitivity, specificity, accuracy, positive predictive value
      (PPV) and negative predictive value (NPV) were calculated for MRI and the nuclear
      medicine studies. RESULTS: For MRI/nuclear medicine, a sensitivity of 100%/77%, a
      specificity of 60%/50%, an accuracy of 79%/61%, a PPV of 69%/58% and a NPV of
      100%/71% were calculated. Four MR examinations were false positives because of
      postsurgical granulation tissue. A high degree of interobserver agreement was
      found on MRI (kappa=0.88). A low-grade infection was missed on two scintigrams,
      while four were false positive because of ectopic haematopoietic bone marrow, and
      in one examination the anatomical distortion resulted in an inaccurate assignment
      of the uptake leading to false positive findings. Image analysis was frequently
      hindered by susceptibility artefacts due to residual abrasions of metallic
      implants after removal of orthopaedic devices (15/18 patients); this led to
      limited assessment in 17% (3/18 patients). CONCLUSION: Acute activity in a
      chronic osteomyelitis can be excluded with high probability if the MRI findings
      are negative. In the first postoperative year fibrovascular scar cannot be
      distinguished accurately from reactivated infection on MRI and scintigraphy may
      improve the accuracy of diagnosis. MRI is more sensitive in low-grade infection
      during the later course than combined BS/IS. Scintigraphic errors due to ectopic,
      peripheral, haematopoietic bone marrow can be corrected by MRI.

PMID- 10963423
TI  - Sonographic evaluation of digital annular pulley tears.
AB  - OBJECTIVE: To evaluate the sonographic (US) appearance of digital annular pulley
      (DAP) tears in high-level rock climbers. DESIGN AND PATIENTS: We performed a
      retrospective analysis of the US examinations of 16 high-level rock climbers with
      clinical signs of DAP lesions. MRI and surgical evaluation were performed in five
      and three patients respectively. The normal US and MRI appearances of DAP were
      evaluated in 40 and three normal fingers respectively. RESULTS: Nine of 16
      patients presented a DAP tear. In eight subjects (seven with complete tears
      involving the fourth finger and one the fifth finger), US diagnosis was based on
      the indirect sign of volar bowstringing of the flexor tendons. Injured pulleys
      were not appreciated by US. Tears concerned the A2 and A3 in six patients and the
      A3 and A4 in two patients. A2 pulley thickening and hypoechogenicity compatible
      with a partial tear was demonstrated in one patient. MRI and surgical data
      correlated well with the US findings. Four patients had tenosynovitis of the
      flexor tendons but no evidence of pulley disruption. US examinations of three
      patients were normal. In the healthy subjects US demonstrated DAP in 16 of 40
      digits. CONCLUSION: US can diagnose DAP tears and correlates with the MRI and
      surgical data. Because of its low cost and non-invasiveness we suggest US as the
      first imaging modality in the evaluation of injuries of the digital pulley.

PMID- 10963424
TI  - Imaging in isolated sacral tuberculosis: a review of 15 cases.
AB  - OBJECTIVE: To review imaging studies of isolated involvement of the sacrum due to
      tuberculosis and determine the role of imaging in the diagnosis and management of
      these patients. DESIGN AND PATIENTS: A retrospective analysis of 15 cases of
      isolated sacral tuberculosis imaged with MR imaging was performed. The CT images
      were also reviewed where available, and the various lesion characteristics were
      identified. We also reviewed the medical records in an attempt to determine the
      impact of the imaging studies on the management of these patients. RESULTS:
      Fifteen patients (5 male, 10 female) presented with symptoms of 3-15 months'
      duration. Chronic localized backache with muscle spasm was the commonest
      presenting symptom; discharging sinuses with abscess formation was found in six
      patients, five of whom were children. MR imaging of the sacrum revealed a
      hypointense marrow signal on T1-weighted images and hyperintense signal on T2
      weighted images in 14 of 15 patients, the S2 vertebra being always involved. CT
      revealed osteolytic changes in the sacrum in all the five patients in whom CT was
      performed. All patients showed marked clinical improvement within 1 year of anti
      tuberculous chemotherapy. CONCLUSION: Isolated tuberculosis of the sacrum is
      uncommon but should be suspected in patients presenting with chronic low backache
      or children with discharging sinuses/abscesses and showing sacral destruction on
      CT or MR imaging. MR imaging can identify cases and enables early institution of
      antituberculous chemotherapy.

PMID- 10963425
TI  - Comparison of supraspinatus tendon and glenohumeral joint axes in MR imaging of
      the shoulder.
AB  - OBJECTIVE: In magnetic resonance (MR) imaging of the shoulder, oblique coronal
      images are used for evaluating the supraspinatus tendon (SST) of patients with
      suspected rotator cuff tear or impingement. This study aimed to compare
      orientation of the SST long axis with planes perpendicular to the glenohumeral
      joint (GHJ). DESIGN AND PATIENTS: The axial scans of 100 consecutive patients
      referred for MR imaging or MR arthrography of the shoulder were reviewed. Using
      the electronic cursors of a computer workstation, the angle of the SST long axis
      was measured and compared with the angle obtained through the GHJ utilizing three
      different landmarks: perpendicular to the joint (GHJ-90), joint-humeral head
      center axis (GHJ-H) and joint-scapular body axis (GHJ-S). RESULTS: Differences in
      angulation between axes of the SST and the three GHJ axes averaged only about 5
      degree [range of means 4.5-5.3 degrees, range of standard deviation (SD) 3.8-4.6
      degrees]. In the majority of shoulders, angular differences measured 4 or less
      for all SST/GHJ comparisons. Similarly, small angular differences in the three
      GHJ axes were found: 4.5 degrees (SD 3.3 degrees) for GHJ-90/GHJ-S, 5.0 degree
      (SD 4.0 degrees) for GHJ-S/GHJ-H and 2.9 degrees (SD 3.0 degrees) for GHJ-90/GHJ
      H. Correlation between the GHJ-90 and GHJ-H axes was particularly good, with
      differences of 4 degree or less in 84% of shoulders. The orientations of the GHJ
      axes and that of the SST long axis are comparable. CONCLUSION: The GHJ may
      potentially be used as a landmark for obtaining oblique coronal images of the
      SST.

PMID- 10963426
TI  - Subcutaneous and musculoskeletal sparganosis: imaging characteristics and
      pathologic correlation.
AB  - OBJECTIVE: To document the imaging characteristics of subcutaneous and
      musculoskeletal sparganosis. DESIGN AND PATIENTS: Ten patients with
      musculoskeletal sparganosis were examined, with a variety of imaging modalities
      including MRI (n=6), ultrasonography (n=8), plain radiography (n=7) and CT (n=1).
      Pathologic correlation was carried out in all cases. RESULTS: Nine lesions
      involved soft tissues, of which seven were in the thigh, two in the trunk and one
      involved a vertebral body. The majority of the lesions in soft tissue were
      confined to the subcutaneous layer but two extended deep into underlying muscles.
      Sonography revealed low-echoic serpiginous tubular tracts (8/8), and an
      intraluminal echogenic structure (4/8). MRI revealed multiple serpiginous tubular
      tracts and peripheral rim enhancement. Two patients showed perilesional soft
      tissue edema. Pathologically, the lesion consisted of a larva surrounded by three
      layers of inflammation: an inner epithelioid granulomatous cell layer, middle
      chronic inflammatory cell layers, and an outer fibrous layer. CONCLUSION: The
      study suggests that if serpiginous tubular tracts are seen at imaging studies,
      musculoskeletal sparganosis should be included in the differential diagnosis.

PMID- 10963427
TI  - Features of calcaneonavicular coalition on coronal computed tomography.
AB  - OBJECTIVE: To determine the findings of calcaneonavicular coalition on coronal
      CT. DESIGN: We retrospectively reviewed the CT scans of 14 calcaneonavicular
      coalitions in eight patients. All coalitions were visible on the axial scans, and
      the diagnosis was confirmed by surgery in five patients. These CT scans were
      compared with scans of ten normal feet. RESULTS: We identified two features of
      calcaneonavicular coalition on coronal CT: lateral bridging (an abnormal bony
      mass lateral to the head of the talus) and rounding of the talus. All eight
      patients demonstrated at least one of these two findings. CONCLUSION: Although
      calcaneonavicular coalition is best seen on axial CT scans of the feet, there are
      two abnormalities, lateral bridging and rounding of the head of the talus, which
      should suggest the diagnosis on coronal CT scans.

PMID- 10963428
TI  - Angiosarcoma associated with chronic lymphedema (Stewart-Treves syndrome) of the
      leg: MR imaging.
AB  - Magnetic resonance (MR) imaging findings of two patients with Stewart-Treves
      syndrome are presented. MR imaging showed edematous changes in the subcutaneous
      fat and skin masses that proved to be angiosarcomas. MR signal intensity of the
      tumor was low compared with fat on T1-weighted images and intermediate and
      heterogeneous on T2-weighted images. In one patient, administration of
      intravenous Gd-DTPA showed marked enhancement in the early phase, which persisted
      until the delayed phase. These finding on dynamic MR imaging may reflect the
      abundant vascular spaces seen in these tumors.

PMID- 10963429
TI  - Collagenous fibroma of the arm: a report of two cases.
AB  - A recently proposed addition to fibrous tumors in soft tissue was first described
      as desmoplastic fibroblastoma and later renamed collagenous fibroma. This tumor
      is clinically and morphologically distinct and benign. However, only a few series
      have been reported, and the clinicopathologic features are not widely recognized.
      We present two cases of collagenous fibroma of the arm. Both patients presented
      with an enlarging, well-circumscribed and mobile soft tissue mass. Magnetic
      resonance imaging showed areas of low signal intensity on both T1- and T2
      weighted sequences. Needle aspiration cytology revealed nondiagnostic samples
      because of the low cellularity of the tumors. Each of the resected tumors was
      composed of low-cellular spindle- to stellate-shaped cells in a fibrous matrix
      with clear margination. After the marginal excisions, no recurrences were
      observed. Clinicians should be aware of this entity to prevent overtreatment,
      because imaging findings and cytologic features are similar to those of desmoid
      tumor.

PMID- 10963430
TI  - 'Cable-maker's clavicle': stress fracture of the medial clavicle.
AB  - A 50-year-old man presented with a non-traumatic painful swelling over the medial
      clavicle. Radiographs showed a poorly defined fracture and the possibility of an
      underlying pathology was raised. Computed tomography suggested a stress fracture.
      This prompted a further, more detailed occupational history to be obtained from
      the patient, which revealed a hitherto undescribed cause of clavicular stress
      fracture and obviated the need for further imaging or biopsy.

PMID- 10963431
TI  - Na+,K+-ATPase: 40 years of investigations.
AB  - Nobel Prize of 1997 in chemistry was awarded to three scientists fruitfully
      working in bioenergetics. J. Walker and P. Boyer were awarded the Prize for
      studies of structure and mechanism of functioning of the H+-transporting
      (mitochondrial) adenosine triphosphatase. The decision of the Nobel Committee was
      not unexpected, since these works were very impressive. Special attention was
      drawn to the fact that the investigations of Walker, the recognized specialist in
      protein structure, made possible the experimental confirmation of regularities in
      the mitochondrial ATPase functioning discovered by P. Boyer. The third member of
      this triumph of bioenergetics is Jens-Christian Skou who described the Na+,K+
      activated ATPase in 1957 and then characterized the enzyme properties in detail.
      Forty years of his scientific biography were devoted to this enzyme. Along with
      accumulation of scientific knowledge, that constituted the fundamental
      contribution to bioenergetics (J.Skou is rightfully considered as one of founders
      of this branch in the present-day biology), the world-wide known school of
      scientists was established, and starting from 1974, members of this school
      organize regular conferences on this enzyme.

PMID- 10963432
TI  - Na+,K+-ATPase: structure, mechanism, and regulation.
AB  - Structural organization of alpha- and beta-subunits of Na+,K+-ATPase in the
      membrane, the enzyme oligomeric structure, and mechanisms of ATP hydrolysis and
      cation transport are considered. The data on the structure of cation-binding
      sites and ion-conductive pathways of the pump are reviewed. The properties of
      isoforms of both subunits are described. Special attention was paid to the ATP
      modifying effect on Na+,K+-ATPase. To explain the rather complex dependence of
      the Na+,K+-ATPase activity on ATP concentration, a hypothesis is proposed, which
      is based on the assumption that the membrane contains the enzyme protomer
      exhibiting high affinity to ATP and an oligomer having low affinity to the
      nucleotide and characterized by positive cooperative interactions between
      subunits. Data on the Na+,K+-ATPase phosphorylation by protein kinases A and C
      are reviewed.

PMID- 10963433
TI  - Electrogenic ion transport by Na+,K+-ATPase.
AB  - Experimental data on the ion electrogenic transport by Na+,K+-ATPase available in
      the literature are analyzed. Special attention is paid to the measurements of
      unsteady-state electric currents initiated by alternating voltage or rapid
      introduction of the substrate. In the final part, a physical model of the Na+,K+
      ATPase functioning is discussed. According to this model, active transport is
      carried out by opening and closing of the access channels used for the sodium and
      potassium exchange between solutions on either side of the membrane. The model
      explains most of the experimental data, although some details (the channel size,
      rates of individual transport steps) need further refinement.

PMID- 10963434
TI  - Subcellular distribution of K+-pNPPase (Na+,K+-ATPase) in the Golgi apparatus of
      developing rat cortical neurons.
AB  - The distribution of K+-pNPPase (Na+,K+-ATPase) activity in the compartments of
      the Golgi apparatus in neurons of the cerebral cortex of young and adult Wistar
      rats was studied by ultrastructural cytochemistry. In adult rats, mainly the cis
      most cisterna was associated with reaction deposits. In 10- and especially in 15
      day-old rats, not only the cis-cisternae, but the cis- and trans-Golgi, as well
      as components of the Golgi stack, also revealed K+-pNPPase activity. The dynamic
      changes of K+ -pNPPase localization in the compartments of the neuronal Golgi
      complexes were discussed with respect to the biochemical evidence concerning the
      building, assembly and processing of Na+,K+-ATPase as plasma membrane
      glycoprotein. It was suggested that the high activity in the Golgi complexes seen
      in 15-day-old rats has to be associated with the advancing myelinization in this
      period and the necessity of Na+,K+-ATPase equipment of nodes of Ranvier.

PMID- 10963435
TI  - Nuclear matrix proteins are carried within peripheral material of mitotic
      chromosomes.
AB  - Immunofluorescent analysis has shown that autoimmune sera M-222 and M-260 are
      bound to interphase nuclei and mitotic chromosomes of the pig embryo kidney cell
      culture. The fluorescent stain is diffuse in nuclei and forms a thin fluorescent
      area around each nucleolus, whereas the nucleolar cores are unstained. The
      periphery of each mitotic chromosome is stained distinctly. After removal of
      histones and DNA by the cell treatment with 2 M NaCl and DNase I, the Hoechst
      33258 staining of nuclei and chromosomes disappears completely, whereas the
      pattern of staining with antibodies is not changed as compared with normal cells.
      Electron microscopy revealed in interphase nuclei after such treatment only
      lamina, residual nucleoli, and the intranuclear matrix network, and antibodies
      are bound just to these elements. Molecular mass of proteins bound to these
      antibodies was determined by immunoblotting. Serum M-260 contained antibodies to
      a single 65 kDa polypeptide, whereas antibodies to two polypeptides of 47 and 65
      kDa were found in M-222. After chromatin removal and revealing nuclear protein
      matrix, M-222 binds only to 65 kDa polypeptides. Thus, peripheral chromosomal
      material is involved in transfer of the nuclear matrix polypeptide to daughter
      nuclei during mitosis.

PMID- 10963437
TI  - Challenge of epidemiological research in the developing world: overview.
AB  - Listing the eight most important aspects of epidemiological research relevant to
      hearing loss, this paper reviews some of the difficulties encountered in trying
      to do such research in the developing world. Various research formats are
      discussed. This paper concludes with a review of what has been reported in the
      world's literature about the incidence and prevalence of sensorineural hearing
      loss in children. The average finding from 34 nations is 1.368 hearing impaired
      per 1,000.

PMID- 10963436
TI  - Gangliosides induce cell apoptosis in the cytotoxic line CTLL-2, but not in the
      promyelocyte leukemia cell line HL-60.
AB  - Gangliosides induce apoptosis in the cells of the IL-2-dependent cytotoxic mouse
      line CTLL-2. Upon incubation with gangliosides for 24 h, their effect resulting
      in appearance of apoptotic cells, falls in a series GM2 > GM3 > GM1 > GD1a > GD1b
      > GT1b. In the presence of rIL-2, apoptosis induced by GM1 is suppressed, whereas
      that induced by GM2 is enhanced (the effect of intracellular agent C2-Cer is
      independent of this cytokine). The GM1-induced apoptosis is cancelled by the
      caspase I inhibitor. The gangliosides under study are not able to induce
      apoptosis in the promyelocyte leukemia cell line HL-60. Physiological aspects of
      the phenomenon found are discussed.

PMID- 10963438
TI  - Attitudes toward hearing-impaired children in less developed countries: a pilot
      study.
AB  - Various anecdotal reports have been presented about attitudes to hearing loss and
      deafness in less developed countries but few studies have addressed this matter
      systematically. In the present study, we have applied a standardised
      questionnaire to 357 teachers from as uniform a sample as possible within 20
      countries in Africa, Latin America, and Asia and compared the results with those
      obtained from 107 teachers in Western Europe. The questions tapped into their
      responses toward developing hearing loss themselves, hearing loss in children
      they encountered. and which group of children with disabilities they would prefer
      to teach. The geographical origins of the teachers influenced all measures except
      their view of the contribution that deaf children could make to society. This was
      influenced solely by the age of the responding teacher.

PMID- 10963439
TI  - Epidemiology of permanent childhood hearing impairment in Estonia, 1985-1990.
AB  - This paper describes a retrospective study of permanent childhood hearing
      impairment (PCHI) > or = 40 dB HL in the better ear in children born between 1985
      and 1990 and resident in Estonia. The prevalence rate of all permanent hearing
      impairment for the birth cohort 1985-1990 was 172 (95 per cent (CI 151-194) per
      100,000 live births and that of congenital impairment was 152 (CI 134-170) per
      100,000. For the congenitally-impaired children, 11 per cent had stayed in a
      neonatal intensive care unit for 48 hours or more, 2 per cent had a craniofacial
      abnormality, and 31 per cent had a family history of PCHI. As for aetiology,
      hereditary causes were stated most frequently in 36 per cent of all of the cases
      of PCHI. The aetiology remained unknown in 34 per cent of cases. Additional
      disabilities were found in 23 per cent of all cases. Specific syndromes were
      recognized in 2 per cent of hereditary cases. The mean age at the confirmation of
      hearing impairment was 46.4 months and at hearing aid fitting 57.0 months. The
      results were compared with other European studies, particularly the Trent study.

PMID- 10963440
TI  - Prevalence and age of identification of permanent childhood hearing impairment in
      Cyprus.
AB  - Permanent childhood hearing impairment is a significant public health issue in
      the United Kingdom and elsewhere. It has effects on the hearing-impaired
      individual's linguistic, psychological, educational, and vocational development.
      Data on prevalence are an essential prerequisite for efficient service planning
      and development. This paper reports the first study to be undertaken in Cyprus to
      investigate the prevalence and the age at identification of permanent bilateral
      (congenital or acquired/late-onset) childhood hearing impairment of 50 dB HL or
      greater. The study was based upon a case ascertainment approach for children born
      between 1979 and 1996. Two methods were employed for the data collection:
      interrogation of case records and questionnaires administered to parents. The
      results for those years in which most cases are likely to have been identified
      showed an estimated prevalence of 1.19/1,000 live births (congenital) and
      0.40/1,000 live births (acquired/late onset), with a mean identification age of
      44.0 months for congenital cases. These findings are discussed with reference to
      the service development needs in Cyprus.

PMID- 10963442
TI  - Incidence/prevalence of sensorineural hearing impairment in Thailand and
      Southeast Asia.
AB  - The Bangkok Otological Center (ISA-HI-lFOS/World Health Organization
      Collaborating Center) carried out a series of prevalence studies of hearing
      impairment throughout Thailand. This report includes background information for
      Thailand and its medical personnel and the results of five studies in different
      regions from 1988 to the present. This report emphasises sensorineural hearing
      loss (SNHL). Study I in three Thai provinces showed SNHL at 18.6 per cent. These
      results were considered abnormally high due to a number of extraneous reasons.
      Study 2 was conducted in 17 provinces in 5 regions and in Bangkok. Results showed
      that 8.3 per cent of those tested had a SNHL. Study 3, The Crown Prince Project,
      involved 21 Crown Prince Hospitals and showed an overall SNHL of 4.6 per cent.
      Study 4 was the Thai-Swedish project, where SNHL was reported at 22.7 per cent.
      Study 5 involved school children aged 6 to 15 in both rural Thailand and Bangkok.
      Results showed SNHL in Bangkok children at 3.5 per cent compared to 3.6 per cent
      in the rural children. After a careful review of the various studies, the overall
      results have been interpreted to suggest that the prevalence of SNHL in Thailand
      is between 3.5 and 5 per cent.

PMID- 10963441
TI  - Overview of audiology in Brazil: state of the art.
AB  - The aim of this paper is to provide an overview of the field of clinical and
      rehabilitative audiology for children and adults in Brazil, while simultaneously
      offering some data and results from several different research studies within the
      country. The theme will address seven main topics: (1) the status of services and
      assistance for the hearing impaired; (2) the results of five different
      institutional research studies showing the main causes of hearing impairment in
      children in the city of Sao Paulo; (3) a review of subjective and objective
      methods for early diagnosis and audiological habilitation of children, including
      parent counseling, hearing aids, and cochlear implants; (4) a discussion of
      hearing conservation in different settings; (5) a brief consideration of
      audiological rehabilitation for hearing-impaired elderly adults in the country;
      (6) the main results of the First and Second Brazilian National Campaigns of
      Deafness Prevention; and (7) conclusions.

PMID- 10963443
TI  - Hearing impairment in Latin America: an inventory of limited options and
      resources.
AB  - The availability of information about prevalence/incidence of hearing impairment
      in Latin American countries is very limited. A questionnaire on the subject was
      mailed to most Latin American and Caribbean countries. The information returned
      by 12 respondents (Argentina, Chile. Columbia, Costa Rica, Cuba, Grenada,
      Guatemala, Mexico, Nicaragua, Panama, Puerto Rico, and Uruguay) was analyzed.
      Data are presented about available epidemiological studies on hearing impairment,
      national registers on deafness, publications on otitis media, and programs on
      hearing screening. Presence of training programs and available human resources in
      the broad field of hearing impairment is also discussed. Estimates of the
      enrollment of deaf children in schools for the deaf is also shown. This review
      concludes that hearing impairment is a low priority for national health systems
      in Latin America. material and human resources are limited, audiology services
      are scarce, and technology continues to be very costly by regional standards.

PMID- 10963444
TI  - Cochlear implants: an international perspective--Latin American countries and
      Spain.
AB  - A questionnaire to determine the status of cochlear implant programs was sent to
      11 countries in Latin America and Spain. General data were collected based on the
      population of each country (1996), estimate of population with hearing disorders
      based on the 10 per cent figure of the World Health Organization. number of
      people with congenital or acquired sensorineural hearing loss, and candidates for
      implantation (children and adults). The survey reports the number of people from
      each country who have been implanted, the cost with respect to per capita annual
      income (PCAI), and how many people with respect to PCAI would cover the cost of a
      country's entire program. Also reported are the number who were implanted pre- or
      post-lingually and the estimate of future new candidates for implantation per
      year. In conclusion, the paper discusses the ethical and socio-economic issues
      for cochlear implantation in so-called third world developing countries.

PMID- 10963445
TI  - Population-based genetic study of childhood hearing impairment in the Trent
      Region of the United Kingdom.
AB  - The objective of the study was to investigate childhood hearing impairment in a
      population-based sample from a genetic perspective. Participants included 82
      families with hearing-impaired children (aged 4-13) previously ascertained in the
      Trent Health Region. A questionnaire was mailed to all families, followed by a
      home visit and Connexin-26 35delG mutation screen. The Connexin-26 35delG
      mutation was identified in seven families (approximately 10 per cent of non
      syndromal hearing impairment). Children of these families were significantly more
      likely than children with other modes of inheritance to have a profound hearing
      loss with a flat audiogram profile. The families of children with a significant
      admission to a neonatal intensive care unit were significantly less likely to
      have had genetic counselling. Eight families visited were found to have features
      suggestive of a genetic syndrome that had not been previously assigned a specific
      diagnosis. The study concluded that hearing-impaired children should be
      investigated systematically according to an agreed-upon protocol, which should
      include Connexin-26 35delG mutation analysis at least for those with severe-to
      profound hearing loss.

PMID- 10963446
TI  - Trypsin inhibitor from Dimorphandra mollis seeds: purification and properties.
AB  - A trypsin inhibitor from Dimorphandra mollis seeds was isolated to apparent
      homogeneity by a combination of ammonium sulfate precipitation, gel filtration,
      ion-exchange and affinity chromatographic techniques. SDS-PAGE analysis gave an
      apparent molecular weight of 20 kDa, and isoelectric focusing analysis
      demonstrated the presence of three isoforms. The partial N-terminal amino acid
      sequence of the purified protein showed a high degree of homology with various
      members of the Kunitz family of inhibitors. This inhibitor, which inhibited
      trypsin activity with a Ki of 5.3 x 10(-10) M, is formed by a single polypeptide
      chain with an arginine residue in the reactive site.

PMID- 10963447
TI  - Isolation and characterization of a serine protease from the sprouts of
      Pleioblastus hindsii Nakai.
AB  - An endopeptidase has been purified from sprouts of bamboo (Pleioblastus hindsii
      Nakai) to electrophoretic homogeneity by four purification steps. Its Mr was
      estimated to be 82 kDa by SDS-PAGE. Enzyme activity was inhibited strongly by
      diisopropyl fluorophosphate, and weakly by p-chloromercuriphenylsulfonic acid,
      but not at all by EDTA or pepstatin, indicating that it was a serine protease.
      The preferential cleavage sites for this protease were found to be large
      hydrophobic and amide residues at the P1 position. The specificity of the bamboo
      serine protease differed from that of cucumisin [EC 3.4.21.25], which cleaved the
      charged amino acid residues at the P1 position.

PMID- 10963448
TI  - Purification and characterization of a NAD+-dependent sorbitol dehydrogenase from
      Japanese pear fruit.
AB  - NAD+-dependent sorbitol dehydrogenase NAD-SDH, EC 1.1.1.14) from Japanese pear
      fruit was purified to apparent homogeneity (single band by SDS-PAGE with silver
      staining), and had a specific activity of 916.7 nKatal/mg protein. The molecular
      of the native enzyme was calculated to be 160 kDa by gel filtration, whereas SDS
      PAGE gave a subunit size of 40 kDa, indicating that the native enzyme is a
      homotetramer. The protein immunologically reacted with an antibody raised in
      rabbit against the fusion protein expressed in E. coli harboring an apple NAD-SDH
      cDNA. The Km, values for sorbitol and fructose were 96.4+/-8.60 and 4239+/-33.5
      mM, respectively, and optimum pH for sorbitol oxidation was 9.0 and 7.0 for
      fructose reduction. Pear NAD-SDH had a very narrow substrate specificity, that
      is, sorbitol, L-iditol, xylitol and L-threitol were oxidized but not any of the
      other alcohols tested. These data suggest the structural importance of an S
      configuration at C-2 and an R configuration at C-4 in the substrate(s). Its
      enzymatic activity was strongly inhibited both by heavy metal ions such as
      mercury, and by thiol compounds, such as L-cysteine. However, the addition of
      zinc ion reversed the enzyme inactivation caused by addition of L-cysteine.

PMID- 10963449
TI  - Redox status of cytochrome oxidase in darkened leaf of C4 crop plants.
AB  - Light is essential for growth, development and various metabolic processes in
      plant. One-third of the whole intact leaf blades of pearlmillet and maize were
      covered (treated leaf) with a black opaque plastic sheet at the middle region for
      15 days. The leaf samples were taken from three regions: basal, middle and
      distal; from treated and parallel untreated leaves (control). Oxygen uptake was
      measured from all the three regions by taking randomized leaf discs. Oxygen
      uptake was nearly the same in all the regions of treated and parallel untreated
      leaf in pearlmillet and maize. Carbon monoxide used at 0.5 mM concentration with
      pearlmillet inhibited oxygen uptake slightly (22%) in covered leaf blade, whereas
      the inhibition with maize leaf at 1.12 mM CO was significantly higher (45%).
      However, CO did not inhibit oxygen uptake in untreated leaf from pearlmillet and
      maize. In contrast. cyanide brought about 33%, inhibition in oxygen uptake at
      0.25 mM with pearlmillet and 60%, with maize at 0.4 mM, irrespective of the fact
      whether a portion of the leaf blade was covered or not with an opaque sheet. The
      results indicate that removing light from a portion of the leaf blade alters the
      redox state of the whole leaf in terms of an increase in the level of the
      ferrocytochrome a3 component of cytochrome c oxidase (cytochrome aa3).

PMID- 10963450
TI  - Leaf sheath cuticular waxes on bloomless and sparse-bloom mutants of Sorghum
      bicolor.
AB  - Leaf sheath cuticular waxes on wild-type Sorghum bicolor were approximately 96%
      free fatty acids, with the C28 and C30 acids being 77 and 20% of these acids,
      respectively. Twelve mutants with markedly reduced wax load were characterized
      for chemical composition. In all of the 12 mutants, reduction in the amount of
      C28 and C30 acids accounted for essentially all of the reduction in total wax
      load relative to wildtype. The bm2 mutation caused a 99% reduction in total
      waxes. The bm4, bm5, bm6, bm7 and h10 mutations caused more than 91% reduction in
      total waxes, whereas the remaining six mutants, bm9, bm11, h7, h11, h12 and h13,
      caused between 35 and 78% reduction in total wax load. Relative to wild-type, bm4
      caused a large increase in the absolute amount of C22, C24 and C26 acids, and
      reduction in the C28 and longer acids, suggesting that bm4 may suppress
      elongation of C26, acyl-CoA primarily. The h10 mutation increased the absolute
      amounts of the longest chain length acids, but reduced shorter acids, suggesting
      that h10 may suppress termination of acyl-CoA elongation. The bm6, bm9, bm11, h7,
      h11, h12 and h13 mutations increased the relative amounts, but not absolute
      amounts, of longer chain acids. Based on chemical composition alone, it is still
      uncertain which genes and their products were altered by these mutations.
      Nevertheless, these Sorghum cuticular wax mutants should provide a valuable
      resource for future studies to elucidate gene involvement in the biosynthesis of
      cuticular waxes, in particular, the very-long-chain fatty acids.

PMID- 10963451
TI  - Role of malonate in chickpeas.
AB  - Analysis of the content and distribution of organic acids in chickpea plants
      (Cicer arietinum L.) showed that malonate was the most abundant acid in roots and
      nodules, whereas malate was the main acid in leaves and stems. The highest
      concentration of malonate in roots was in the apices. Malonate metabolism did not
      appear to be directly related to abiotic stress. We suggest that malonate has a
      role as a defensive chemical in roots and nodules of chickpeas.

PMID- 10963452
TI  - Stereostructure and anti-inflammatory activity of three diastereomers of
      ocobullenone from Ocotea bullata.
AB  - A novel diastereomer of ocobullenone. designated as sibyllenone, was isolated
      from the stem bark of mature Ocotea bullata in the course of a search for anti
      inflammatory compounds from this plant. The stereostructure was established by X
      ray crystallography and corroborated by NOESY analysis. Ocobullenone, obtained
      previously, was re-isolated and crystallised successfully for X-ray analysis,
      thus making possible an accurate spatial comparison of ocobullenone, iso
      ocobullenone and the new stereoisomer. Tested pharmacologically for
      cyclooxygenase-1 and 2, and 5-lipoxygenase inhibition, sibyllenone was the only
      compound from O. bullata which showed good inhibitory activity towards 5
      lipoxygenase.

PMID- 10963453
TI  - Sphaerolone and dihydrosphaerolone, two bisnaphthyl-pigments from the fungus
      Sphaeropsidales sp. F-24'707.
AB  - Two new bisnaphthalene compounds, sphaerolone (1) and dihydrosphaerolone (2),
      together with 2-hydroxyjuglone (9), were isolated from the culture broth of a
      Sphaeropsidales sp. (strain F-24'707) after inhibition of the regular proceeding
      1,8-dihydroxynaphthalene (DHN) biosynthesis with tricyclazole. The structures of
      1 and 2 were established by detailed spectroscopic analysis and present novel
      bisnaphthalenes. The biosynthetic origin of 1 and 2 as dimerization products of
      1,3,8-trihydroxynaphthalene, an intermediate of the DHN biosynthesis, is
      discussed.

PMID- 10963454
TI  - Constituents of various wood-rotting basidiomycetes.
AB  - Phytochemical investigation of n-hexane and methanol extracts of fruiting bodies
      of the wood-rotting fungi Fomitopsis pinicola. Ganoderma lipsiense, Fomes
      fomentarius and Gloeophyllum odoratum led to the isolation and identification of
      several triterpene derivatives and some aromatic compounds derived from lignin.
      These are the new natural products, namely, pinicolic acid E (16alpha-hydroxy-3
      oxolanosta-8,24-dien-21-oic acid) and pinicolol C (3-oxolanosta-7,9(11),24-trien
      15alpha,21-diol) from the crust of F. pinicola, ganoderenic acid D [(E)-7beta
      hydroxy-3,11,15,23-tetraoxolanosta-8,20(22)-di en-26-oic acid] and ganoderic acid
      N (7beta,20-dihydroxy-3,11,15,23-tetraoxolanost-8-en-26-oic acid) from G.
      lipsiense and ergosterol peroxide (5alpha,8alpha-epi-dioxyergost-6-en-3beta-ol)
      as well as ergost-7-en-3-one from F. fomentarius. From G. odoratum,
      dehydroeburicoic acid [24-methylene-3-oxolanosta-7,9(11)-dien-21-oic acid], the
      dimethylacetal of 4,4,14alpha-trimethyl-24-oxo-5alpha-chol-8-en-21-oic acid and
      some aromatic compounds, of which 1-(4'-methoxyphenyl)-1,2-ethandiol is a new
      natural product, were isolated. Furthermore, a complete set of 13C NMR data of
      the steryl esters 3beta-linoleyloxyergosta-7,24(28)-diene, 3beta
      linoleyloxyergosta-7,24-diene and 3beta-linoleyloxyergost-7-ene, which could be
      identified as a mixture in all investigated fungi, could be recorded. It was
      proved by HPLC and TLC investigations, that the crust on top of the fruiting
      bodies of F. pinicola consists of lanostane derivatives.

PMID- 10963455
TI  - Flavonoids from the stem bark of Lonchocarpus xuul.
AB  - The stem bark of Lonchocarpus xuul (Leguminosae) has yielded four flavonoids
      which have been identified by spectroscopic methods as the novel 4beta,5
      dimethoxy-6",6"-dimethyl-2H-pyrano-(2",3":7,6)-fl avan (xuulanin), 3beta,4beta,5
      trimethoxy-6",6"-dimethyl-2H-pyrano-(2",3":7,6 )-flavan (3beta-methoxyxuulanin).
      4beta-ethoxy-5-methoxy-6",6"-dimethyl-2H-pyrano-(2",3":7,6)- flavan (4beta
      demethylxuulanin-4beta-ethyl ether), and the known 5,7-dihydroxy-6,8-di(3
      methylbut-2-enyl)flavanone (spiniflavanone-B). The ethyl derivative is considered
      likely to be an artefact.

PMID- 10963456
TI  - Characterization of some O-acetylated saponins from Quillaja saponaria Molina.
AB  - Sixteen saponins were identified from a bark extract of Quillaja saponaria
      Molina. The compounds were characterized, using NMR spectroscopy, mass
      spectrometry and monosaccharide analysis, as quillaic acid substituted at C-3
      with oligosaccharides consisting of a disaccharide, beta-D-Galp-(1-->2)-beta-D
      GlcpA substituted with either D-xylose or L-rhamnose and at C-28 with complex
      oligosaccharide structures consisting of a disaccharide, alpha-L-Rhap-(1-->2)-4-O
      acetyl-beta-D-Fucp, substituted with various amount of D-xylose. D-glucose, D
      apiose, and L-rhamnose.

PMID- 10963457
TI  - Further sesquiterpene lactones from Anthemis carpatica.
AB  - A new germacranolide, (E)-1alpha, 10beta-epoxy-3beta-acetoxy-6alpha
      hydroxygermacra-4,11 (13)-dien-12,8alpha-olide, together with nine new highly
      oxygenated guaiadien-12,6alpha-olides of anthemolide, and cumambrin type were
      identified in the repeated examination of the aerial parts of the flowering
      Anthemis carpatica. In addition, six known guaianolides belonging to the same
      groups, also isolated previously from A. carpatica, along with two guaianolides,
      2beta-hydroxyepiligustrin and cumambrin B, not found before in this species, were
      isolated this time.

PMID- 10963458
TI  - Glycosidic compounds of murolic, protoconstipatic and allo-murolic acids from
      lichens of Central Asia.
AB  - Eleven compounds isolated from the extract of the Central Asian lichens comprised
      eight new glycosides having murolic, protoconstipatic and allo-murolic acids, as
      the aglycones and a saccharide moiety linked at C-18 made up of one or two sugars
      (glucose and apiose or rhamnose or xylose or arabinose). The structures were
      elucidated by using extensive spectroscopic analysis (1D and 2D NMR, MS, IR, UV
      and CD) and chemical methods.

PMID- 10963459
TI  - Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and
      serendipity.
AB  - Some clinicians and alternative therapy practitioners advocate megadose
      intravenous and oral ascorbate treatment of cancer. Randomized control studies
      using oral ascorbate showed no benefit. Recent data show that intravenous but not
      oral administration of ascorbate can produce millimolar plasma concentrations,
      which are toxic to many cancer cell lines. We propose that ascorbate treatment of
      cancer should be reexamined by rigorous scientific scrutiny in the light of new
      evidence.

PMID- 10963460
TI  - Plant residue and bacteria as bases for increased stool weight accompanying
      consumption of higher dietary fiber diets.
AB  - OBJECTIVE: Stool diluting effects of relatively inert material, such as
      unfermentable dietary fiber, has been proposed as an effect of fiber beneficial
      to the colon. Stool dilution by increasing bacterial mass may be beneficial or
      deleterious, depending on bacterial metabolic products. The purpose of this study
      was to determine the basis for stool weight when two stepwise increases of fiber
      from all classes of fiber-containing foods were consumed. METHODS: Stool from
      five men consuming three constant diets containing 15, 30 and 42 g/d of dietary
      fiber were fractionated into plant material and bacteria and analyzed for neutral
      and amino sugar content. Fecal nitrogen, fat and ash were measured. RESULTS:
      Daily gravimetric yield and sugar content of the plant fraction from stool
      increased with each fiber addition. Compared to the low fiber diet, the medium
      fiber diet decreased the concentration of the bacterial mass in wet stool by 11%
      and the high fiber diet by an additional 32%. The high fiber diet decreased stool
      fat concentration; the medium and high fiber diets decreased stool nitrogen
      concentration to the same extent. Apparent digestibility of plant-derived neutral
      sugars decreased with each fiber addition. CONCLUSIONS: Inherently less
      fermentable plant material modulates the colon environment in three beneficial
      ways: it is a relatively unreactive diluent of lumenal contents; it adds mass to
      promote distal movement of waste; it does not promote a large bacterial mass.

PMID- 10963461
TI  - Free amino acid content in standard infant formulas: comparison with human milk.
AB  - OBJECTIVE: To compare the concentration of non-protein nitrogen (NPN) and free
      amino acids (FAA) in powdered and liquid commercial formulas with that in human
      milk. METHODS: The non-protein nitrogen and FAAs in pooled breast milk was
      compared with that in 11 protein-modified starting infant formulas (seven
      powdered, four liquid whey-predominant formulas) and one powdered soy-formula.
      Human milk was collected at the end of each feeding (hindmilk) over 24 hours in a
      group of 40 healthy lactating women after delivery of full-term infants at age
      one month. RESULTS: In human milk glutamic acid plus glutamine and taurine were
      the prevalent amino acids, accounting for around 50% total FAA. In the analysed
      formulas the total FAA fraction was 10% or even less than in human milk, mostly
      represented by taurine, while methionine was high in soy formula. The sum of
      glutamic acid and glutamine in all the formulas was much lower than in human
      milk. CONCLUSIONS: Breastfed infants are supplied with FAA, mainly glutamic acid
      and glutamine, compared to formula-fed counterparts. The different FAA intake
      might be the origin of some functional differences at the enteral level between
      breast- and formula-fed infants.

PMID- 10963462
TI  - Assessment of healthcare professionals' knowledge about warfarin-vitamin K drug
      nutrient interactions.
AB  - OBJECTIVE: Dietary vitamin K can interact with oral anticoagulant drugs and
      interfere with their therapeutic safety and efficacy. Therefore, knowledge about
      drug-nutrient interactions involving vitamin K possessed by physicians,
      pharmacists, dietitians and nurses practicing anticoagulant therapy was assessed.
      METHODS: Healthcare practitioners were surveyed using a 30-question, 98-item
      questionnaire on the most common and/or important food interactions with
      warfarin, drug interactions with warfarin and general drug-nutrient interactions
      involving vitamin K. The study sample included 160 randomly selected healthcare
      providers (40 physicians, pharmacists, dietitians and nurses) from 10 hospitals
      with 200 to 1000 beds from six Massachusetts regions. Random selection was
      conducted from a pool of selected healthcare providers practicing anticoagulant
      therapy who counsel patients receiving warfarin. RESULTS: All surveys were
      completed within three months of the start of the study, and all participants
      provided usable data for statistical analysis. The mean scores (+/- SD) on the
      overall test were 72.5+/-9.0 for pharmacists, 62.51+/-10.6 for physicians, 56.9+/
      8.8 for dietitians and 50.2+/-9.3 for nurses, with 100 being a perfect score.
      Pharmacists scored significantly higher in the area of drug interactions (75.9+/
      11.3, p<0.05). Dietitians scored higher in the area of food interactions (73.0+/
      10.3). No significant differences between physicians and pharmacists were evident
      on general drug-nutrient interactions. While over 87% of the healthcare
      professionals correctly identified some common foods containing large amounts of
      vitamin K, such as broccoli and spinach, fewer than 25% were able to identify
      others such as pea soup, coleslaw and dill pickles. CONCLUSIONS: Although the
      healthcare professionals surveyed in this study appear to have demonstrated some
      proficiency in their respective areas of expertise, they exhibited less knowledge
      in others. Therefore, additional training and integration of knowledge and
      expertise about drug-nutrient interactions among healthcare professionals are
      essential to provide appropriate patient counseling and optimal therapeutic
      outcomes.

PMID- 10963463
TI  - Placement of nasoenteral feeding tubes using magnetic guidance: retesting a new
      technique.
AB  - OBJECTIVE: To study a new technique of intubating the small bowel using a newly
      developed nasoenteral feeding tube fitted with a magnet in its tip and guided for
      placement with an external magnet. METHODS: The study was performed in medical
      and surgical wards of a university-affiliated Department of Veterans Affairs
      hospital on 42 patients referred by their attending physicians for tube
      placement. The newly designed feeding tube was inserted per nares into the
      stomach using traditional technique. As the tube was advanced, movement of the
      hand-held steering magnet was designed to guide the tip of the magnetic
      nasoenteral tube along the lesser curvature of the stomach, through the pyloric
      sphincter, and into the duodenum. Portable abdominal radiography confirmed the
      anatomic location of the tube tip. RESULTS: Fifty-one intubations were performed
      on 42 subjects. In 45 intubations (88%), tubes passed into the duodenum. Twenty
      seven (53%) met criteria for optimal placement in the second portion of the
      duodenum or distally. Six of 11 tubes (55%) that were not optimally placed were
      advanced to the distal duodenum on repositioning. Median procedure time for the
      initial intubations was 30 minutes (interquartile range 15-40). Median procedure
      time for last 10 intubations improved to 13 minutes (interquartile range 5-20).
      No complications were related to the procedure. CONCLUSIONS: Enteral feeding tube
      placement using external magnetic guidance is a promising, novel technique which
      is deserving of further study.

PMID- 10963464
TI  - Increased plasma homocyst(e)ine after withdrawal of ready-to-eat breakfast cereal
      from the diet: prevention by breakfast cereal providing 200 microg folic acid.
AB  - OBJECTIVE: We tested the hypothesis that cessation of habitual ingestion of
      breakfast cereals would be associated with elevated plasma homocyst(e)ine
      concentrations. We anticipated that those subjects who reported consuming
      breakfast cereals containing 100 to 400 ,microg of folic acid per serving before
      entering the study would achieve higher plasma homocyst(e)ine concentrations if,
      in addition to their regular diet, they began ingesting a daily serving of
      breakfast cereal that contained less than 10 microg of folic acid per serving.
      DESIGN: Seventy-nine subjects consumed a daily serving of breakfast cereal
      containing either < 10 microg or folic acid per serving (placebo) or breakfast
      cereal containing 200 microg of folic acid per serving (folic acid fortified).
      RESULTS: Cessation of intake of commercially available breakfast cereal was
      associated with homocyst(e)ine elevation. Breakfast cereal containing 200 microg
      folic acid per day was sufficient to maintain the homocyst(e)ine lowering effects
      of commercial cereals. CONCLUSIONS: Habitual consumption of commercially
      available fortified breakfast cereals, usually containing 100 to 400 microg folic
      acid per serving, had significant homocyst(e)ine lowering effects as shown by the
      homocyst(e)ine increase after cessation of habitual intake of commercial
      breakfast cereal. Substitution of breakfast cereal containing only 200 microg
      folic acid per day was sufficient to maintain the homocyst(e)inelowering effects
      of commercial cereals.

PMID- 10963465
TI  - Effects on cholesterol balance and LDL cholesterol in the rat of a soft-ripened
      cheese containing vegetable oils.
AB  - OBJECTIVE: The purpose of this study was to examine effects of a modified soft
      ripened cheese containing vegetable oils on cholesterol status, using the rat as
      the experimental model and the traditional soft-ripened cheese as the control.
      METHODS: Adult male Wistar rats (approximately 370 g) were divided into two
      dietary groups (20 rats/group) and fed either the standard diet (STD, containing
      traditional cheeses made from whole milk) or the experimental diet (EXP,
      containing modified cheeses made from the combination of skim milk with the
      following fat mixture: milk fat/oleic acid-enriched sunflower oil/soybean oil
      mixture). Lipids of the diets came solely from cheeses (14 g/100 g diet); the EXP
      diet contained (3-fold) less saturated fat, (2-fold) less cholesterol, and (15
      fold) more phytosterols than the STD diet. RESULTS: Although serum triglyceride
      and total cholesterol concentrations were not affected by the type of diet, the
      EXP diet resulted in a significant reduction of LDL-cholesterol (31%, p < 0.001)
      and a significant increase of HDL-cholesterol (11%, p < 0.05), compared to the
      STD diet. Thus, a marked reduction (39%) of serum LDL/HDL cholesterol ratio was
      observed in the EXP group (p < 0.001). In addition, the two quantitative balances
      (excreted/ingested) of cholesterol and total neutral sterols (for which
      phytosterols were excluded) were significantly higher by 183% and 174%,
      respectively for the EXP group, compared to the STD group (p < 0.05). On another
      hand, rats fed the EXP diet excreted more cholesterol than they ingested dietary
      cholesterol (cholesterol balance > 1), indicating that those animals eliminated
      some endogenous cholesterol in their feces, while the opposite was true for rats
      fed the STD diet (cholesterol balance < 1). Finally, fecal bile salt
      concentration was not significantly different between the two dietary groups.
      CONCLUSIONS: The partial substitution of milk fat by vegetable oils in soft
      ripened cheese resulted in a decreased blood LDL/HDL cholesterol ratio and an
      increased fecal excretion of endogenous cholesterol and neutral sterols and,
      thus, markedly improved its nutritional qualities. Therefore, the consumption of
      the described modified cheese may meet the demand of subjects who wish to lower
      their risk for atherosclerosis and cardiovascular disease.

PMID- 10963466
TI  - Examining associations of brain aging with midlife tofu consumption.

PMID- 10963467
TI  - Influence of conjugated linoleic acid (CLA) on establishment and progression of
      atherosclerosis in rabbits.
AB  - OBJECTIVE: To determine effects of conjugated linoleic acid (CLA) on
      establishment and progression of experimentally-induced atherosclerosis in
      rabbits. METHODS: For establishment of atherosclerosis, New Zealand White rabbits
      were fed a semipurified diet containing 0.1% to 0.2% cholesterol for 90 days.
      Some groups were fed diet and CLA. For effects on progression of atherosclerosis,
      rabbits with established atherosclerosis were fed a semipurified diet +/- CLA for
      90 days. RESULTS: At dietary levels as low as 0.1%, CLA inhibited atherogenesis.
      At dietary levels of 1%, CLA caused substantial (30%) regression of established
      atherosclerosis. This is the first example of substantial regression of
      atherosclerosis being caused by diet alone. CONCLUSION: Dietary CLA is an
      effective inhibitor of atherogenesis and also causes regression of established
      atherosclerosis.

PMID- 10963468
TI  - Conjugated linoleic acid and bone biology.
AB  - Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of
      people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and
      induce cartilage degradation for which part of the response is mediated by PGE2.
      Excess production of PGE2 is linked to osteoporosis and arthritis and is
      associated with bone and proteoglycan loss. PGE2 also influences the IGF-I/IGFBP
      axis to facilitate bone and cartilage formation. Recent investigations with
      growing rats given butter fat and supplements of CLA demonstrated an increased
      rate of bone formation and reduced ex vivo bone PGE2 production, respectively.
      Furthermore, the supplements of CLA isomers resulted in their enrichment in
      lipids of various bone compartments of animals. The effects of CLA on bone
      biology in rats (IGF action and cytokines) appear to be dependent on the level of
      n-6 and n-3 fatty acids in the diet; however, these studies generally showed that
      CLA decreased ex vivo bone PGE2 production and in osteoblast-like cultures. Anti
      inflammatory diets, including nutraceutical applications of CLA, may be
      beneficial in moderating cyclooygenase 2 (COX-2) activity or expression
      (influencing PGE2 biosynthesis) and might help to reduce rheumatoid arthritis
      (secondary osteoporosis). This review summarizes findings of CLA on bone modeling
      in rats and effects on cellular functions of osteoblasts and chondrocytes. These
      experiments indicate that CLA isomers possess anti-inflammatory activity in bone
      by moderating prostanoid formation.

PMID- 10963469
TI  - Changes in body composition with conjugated linoleic acid.
AB  - Conjugated linoleic acid has been shown to reduce body fat accumulation in
      several animal models. We have conducted several studies in AKR/J mice showing
      that CLA reduces body fat accumulation whether animals are fed a high-fat or low
      fat diet, with no effect on food intake. One mechanism by which CLA reduces body
      fat is by increased energy expenditure, which is observed within one week of CLA
      feeding and is sustained for at least six weeks. The increased energy expenditure
      is sufficient to account for the decreased fat accumulation. Increased uncoupling
      protein gene expression does not appear to be involved in the increased energy
      expenditure. We have observed increased fat oxidation but no decrease in de novo
      fat biosynthesis with CLA feeding. We have also observed increased liver weights
      and plasma insulin levels with higher doses of CLA. In all of the studies we have
      conducted to date we have used a CLA preparation that contains several isomers,
      primarily c9,t11 and t10,c12. It was assumed that the active form was c9,t11, as
      CLA was identified as an anticarcinogenic compound from cooked beef, of which the
      c9,t11 form accounts for 60% to 80% of the CLA. Most of the studies conducted so
      far must be repeated using the purified isomers in order to determine which
      isomers are responsible for each of the identified actions of CLA.

PMID- 10963470
TI  - Overview: epilepsy surgery in developing countries.
AB  - Epilepsy surgery (ES) is addressed in relation to economic classifications of
      national resources and welfare in developing countries. A decade ago, ten
      developing countries conducted ES; now 26 such countries have reported results of
      ES. A number of international authorities define indicators of national economic
      welfare. Adopting the economic classification of the International Monetary Fund.
      we find that ES is nonexistent in 98% of African countries, 76% of Asian
      countries, 58% of European countries, 82% of Middle East countries, and in 86% of
      countries of the Western Hemisphere. The 1980-1990 global ES survey conducted by
      the International League Against Epilepsy identified ten developing countries
      reporting ES (DCRES): Brazil, China, Czechoslovakia, Hungary, Mexico, Poland,
      Taiwan, the U.S.S.R., Yugoslavia, and Viet Nam. The present survey based on the
      proceedings of the 19th-23rd International Epilepsy Congresses and Medline
      reports from 1991 to November 1999 revealed at least 26 (18.3%) DCRES of 142
      developing countries: Argentina, Brazil, Chile, China, Colombia, Czech Republic,
      Egypt, Estonia, Hungary, India, Iran, Israel, Korea, Lithuania, Mexico,
      P.R.China, the U.S.S.R., Singapore, Slovenia, South Africa, South Korea, Taiwan,
      Turkey, Ukraine, Uruguay, and former Yugoslavia. National vital statistics expose
      the hardships of developing countries. The population ratio of developed
      countries to developing countries is approximately 1:5. The reverse per capita
      Gross Domestic Product ratio is 20:1. Great disparities exist in vital
      statistics, all to the disadvantage of the DCRES. The World Health Organization
      defines health-related sectors geographically, then divides developing countries
      into several subgroups. Disability caused by length of disease and years lived
      with disability can be quantified monetarily for epilepsy, and the total health
      expenditures of developed and developing countries can be compared. The DCRES are
      short of technology, and their ES teams must choose from an excess of surgical
      candidates, investigating with computed tomography, magnetic resonance imaging,
      noninvasive video-electroencephalography, and neuropsychology. The surgical
      outcomes achieved are similar to those in the developed world, but at a
      fractional cost. To internationalize ES, outcome, cost, and savings from care,
      evolution of assessment methodology is needed. Also needed is general support
      from the developed world.

PMID- 10963471
TI  - Medical and surgical strategies for epilepsy care in developing countries.
AB  - Epilepsy is a major health problem, and there is hope that current international
      initiatives--epitomized in the "Epilepsy: Out of the Shadows" campaign--will
      increase the commitment of the general public and health officials to the care of
      patients. Particularly in developing countries, there is great need for
      alleviation of the extremely difficult situation of people with epilepsy and
      their families. Doctors can play their part by adhering to specific medical and
      surgical strategies aimed at the improvement of epilepsy care in these countries.
      Included in the former are joining efforts to guarantee a regular distribution of
      conventional antiepileptic drugs (AEDs), make optimal use of the more easily
      available AEDs, and improve communication with patients and families at all
      levels. It is also important to support the creation of local and regional
      specialized epilepsy centers with the capability to perform presurgical
      evaluation and epilepsy surgery in many patients with medically refractory
      seizures. The establishment of such centers in developing countries will face
      several challenges, including a critical view of technological advances and the
      need to support well-trained, creative people who can evaluate and operate on
      patients with relatively limited resources. This article proposes that the
      success of such an approach depends on the progressive build-up of a "critical
      mass" of specialized people who are trained locally to select or reject epilepsy
      patients for surgery using the available resources. A stepwise approach to the
      increasing levels of complexity involved in the evaluation and surgical treatment
      is proposed, with the expectation that each center will find its level and adhere
      to its capability.

PMID- 10963472
TI  - Temporal lobe epilepsy surgery with limited resources: results and economic
      considerations.
AB  - This study evaluates the surgical outcome of patients with medically refractory
      temporal lobe epilepsy (TLE) who underwent anterior temporal lobe lobectomy (ATL)
      based on data derived from noninvasive studies and assesses the economic costs
      entailed at a newly created epilepsy program in Chile. Seventeen ATL candidates
      underwent a presurgical evaluation. This included outpatient brain MRI and
      neuropsychological testing and inpatient scalp/sphenoidal prolonged video-EEG
      monitoring. There were 10 females and 7 males, with a mean age of 23.8 years and
      a mean duration of seizure disorder of 12 years. Patients with congruent data
      localizing the seizure focus to one anterotemporal region underwent ATL. Seven
      patients underwent a left-side ATL and 10 patients a right-side ATL. The
      histopathological findings showed a low grade tumor in six patients, hippocampal
      sclerosis in five, neuronal migration disorder in four, and cavernous angiomas in
      two patients. The mean follow-up period was 29.1 months. Seizure outcome was
      assessed with Engel's classification: class I, no seizures or only auras; class
      II, rare seizures; class III, >90% seizure reduction; class IV, <90% seizure
      reduction. Fifteen patients are now in class I, one patient in class II, and one
      in class IV. The total cost, including evaluation and surgery, was equivalent to
      US$ 5,020. Thus, well-selected TLE patients can derive maximal benefit from ATL
      after a noninvasive presurgical evaluation. This finding is of great significance
      for the creation of epilepsy surgery programs in developing countries.

PMID- 10963473
TI  - Corpus callosotomy in Colombia and some reflections on care and research among
      the poor in developing countries.
AB  - The authors present the results of a series of corpus callosotomies (CCS) in 97
      patients performed from 1989 to 1997 at the Hospital Neurologico of the Liga
      Colombiana Contra La Epilepsia, Cartagena, Colombia. This study demonstrates the
      feasibility of performing these procedures in the developing world and analyzes
      the outcome and cost of treatment. Patients with medically intractable
      secondarily generalized epilepsy, bilateral nonfocal epileptic
      electroencephalogram (EEG), and absence of progressive encephalopathy were
      accepted as candidates (patients aged 0-30 years; 62 children, 19 girls and 43
      boys, with mean age at surgery of 7.9 years; 35 adults, 19 women and 16 men, with
      mean age at surgery of 25.8 years). Preoperatively, the mean seizure frequency
      was 12.1 per day, or 364 per month (range, 0.06-200 per day, 1.8-6000 per month).
      Before surgery, 40% of patients were classified with generalized tonic-clonic
      seizures of different etiologies, or cryptogenic seizures; 36% had mixed
      seizures; 19% had Lennox-Gastaut Syndrome; and 5% had West Syndrome. Usually,
      routine EEG, computed tomography, and clinical findings sufficed for the surgical
      decision. The standard microsurgical technique performed was an anterior two
      thirds CCS by the same surgeon under general anesthesia. In five cases, an
      additional frontal lobe excision after electrocorticography and subdural
      electrode monitoring was carried out in the same session. The results were
      evaluated after a mean follow-up of 35 months (range, 12-28). Two thirds of
      patients became seizure-free or were left with none or some disabling seizures.
      AED medication was eased slightly after surgery. The complication rate was low.
      The patients underwent postoperative psychosocial studies and neuropsychological
      rehabilitation and showed tendencies toward improvement. The direct cost of CCS
      in U.S. dollars (US$) ranged between 3,137 and 3,995 depending on the
      preoperative studies. Thus, CCS is well suited for selected patients in
      developing countries. Thus far, implantation of a vagus nerve stimulator has
      exceeded our economic possibilities in treating similar patients. Some
      reflections on care and research among epilepsy patients in developing countries
      are discussed.

PMID- 10963474
TI  - Mutual benefits from epilepsy surgery in developed and developing countries.
AB  - The last three decades have seen tremendous progress in the surgical management
      of patients with intractable epilepsy involving all facets of diagnosis,
      localization, operative technique, and research. Unfortunately, such progress has
      taken place and is in operation only in the developed countries of North America,
      Europe, and Japan. Epilepsy surgery programs in the developing countries of South
      America, Asia, and particularly Africa, if they exist at all, are the result of
      the individual efforts of physicians who were fortunate enough to receive their
      training abroad. These physicians face difficulties in financing their programs
      and in obtaining the necessary equipment, and they work without the assistance of
      trained personnel or technicians. The exchange of experience between physicians
      in developed and developing countries may be mutually beneficial. In the face of
      the high cost of health care in developed countries, it is unrealistic to expect
      patients with intractable epilepsy to continue to undergo elaborate investigative
      procedures indefinitely. On the other hand, physicians in developing countries
      need to keep updated on the latest technology and research and have to receive
      the necessary support from developed countries to slowly build up their programs.
      The global perspective of physicians dealing with epilepsy patients may be
      broadened by exposure to the experience from the "other side of the fence" and
      will ultimately lead to better patient education and more focused patient care.

PMID- 10963475
TI  - Is epilepsy surgery possible in countries with limited resources?
AB  - This study illustrates the outcome and cost-effectiveness of anterior temporal
      lobectomy (ATL) among patients with medically refractory temporal lobe epilepsy
      (TLE) treated in an epilepsy center in Kerala, South India. Patients for ATL were
      selected on the basis of a noninvasive protocol comprising clinical, interictal
      scalp electroencephalogram (EEG), magnetic resonance imaging, and ictal video-EEG
      data. The authors compared the outcome and direct cost of 119 patients (mean age,
      25.6 years; mean duration of epilepsy before ATL, 16.1 years) who have completed
      at least 1 year follow-up after ATL with 71 refractory TLE patients (mean age,
      27.1 years; mean duration of epilepsy, 15.4 years) who did not undergo ATL.
      Patients in the study who underwent ATL had a 70% likelihood of becoming seizure
      free after ATL and a 30% chance of being completely off of antiepileptic drug
      treatment within 3 years after ATL. The out-of-pocket one-time payment for ATL
      (including presurgical evaluation) in this setup is Indian Rupees (INR) 47,000
      (US$ 1,200). The total direct medical cost of caring for TLE patients aged 26 to
      60 years would be INR 200,000 (US$ 5,000). Patients freed from seizures often can
      be better employed and achieve an improved quality of life. It is concluded that
      ATL for refractory TLE is a more cost-effective option than continued medical
      treatment. Epilepsy surgery is not only possible in a developing country but can
      also be undertaken in a cost-effective way.

PMID- 10963476
TI  - Comparison of the epilepsy surgery programs in Cartagena, Colombia, and Zurich,
      Switzerland.
AB  - The organization, financing, productivity, quality of work, and cost
      effectiveness of the Epilepsy Center in Cartagena, Colombia, were studied and
      compared with the epilepsy surgery program at the University Hospital Zurich,
      Switzerland. During a 2-month visit, one of the authors (I.T.) evaluated the
      center in Cartagena as a welfare institution and evaluated its epilepsy surgery
      program. The postoperative results of the Cartagena program were compared with
      those reported at the Second International Palm Desert Conference 1992, which
      revealed a similar rate of postoperative seizure control in temporal lobe
      epilepsy, slightly inferior results with hemispherectomy, and slightly better
      results with anterior callosotomy. A comparison between the two epilepsy centers
      showed that pre and postoperative antiepileptic drug treatment is more restricted
      in Colombia because of high costs. Although important diagnostic tools such as
      electroencephalography, seizure monitoring, neuropsychology, computed tomography,
      and magnetic resonance imaging are available in both centers, the Zurich program
      also has access to positron emission tomography, single photon emission computed
      tomography, magnetic resonance spectroscopy, and intracarotid and selective
      amobarbital tests. The postoperative seizure outcome is similar in surgical
      temporal lobe epilepsy patients (temporal lobectomy series, Cartagena; selective
      amygdalohippocampectomy series, Zurich). The comparison of direct costs of
      epilepsy surgery in Cartagena and Zurich showed that for the average patient
      undergoing epilepsy surgery in Cartagena, the cost is 5.5% of that in Zurich.
      This study presents evidence that epilepsy surgery is an inexpensive and
      efficient treatment option for epilepsy patients in developing countries.
      Epilepsy surgery in developing countries may even be considered at an early stage
      in patients who cannot afford the costs of lifetime medical treatment but can
      afford the one-time cost of a surgical treatment.

PMID- 10963477
TI  - Surgical outcome of epilepsy patients evaluated with a noninvasive protocol.
AB  - Surgery is now an accepted treatment for some medically intractable epilepsies.
      Presurgical evaluation is particularly important for the localization of the
      epileptogenic zone, which may necessitate sophisticated imaging techniques and
      intracranial electroencephalogram (EEG) recordings. If patients are carefully
      selected, however, successful results can be achieved with noninvasive evaluation
      methods. Seventy-seven patients were operated on for intractable seizures. All
      patients underwent EEG, neuropsychological, psychiatric, and magnetic resonance
      imaging investigations. Ictal EEG-video recording was performed in all
      nonlesional and in some lesional cases that had discordant data. Selective
      amygdalo-hippocampectomy was performed on patients with mesial temporal lobe
      epilepsy (MTLE), an extended or a limited lesionectomy was performed on patients
      with structural lesions, and a lesionectomy with deafferentation was performed on
      two patients with West syndrome. Electrocorticography was not used. Temporal lobe
      directed surgery was performed in 63.6% of the cases. The pathological
      examinations of all cases showed hippocampal sclerosis (HS) in 43%, tumor or
      tumor-like lesions in 36%, and cortical dysplasia in 5% of patients. After a mean
      follow-up of 17 months (range, 2-53), 75% of the patients were seizure-free with
      or without aura and 15% had a marked improvement, whereas 10% did not benefit
      from surgery. Neuropsychological outcome of patients with MTLE and HS also showed
      worthwhile results. Our patients, who were evaluated without pre- and
      perioperative intracranial recordings and other sophisticated techniques, had an
      outcome comparable to those in other series from more experienced centers. Our
      experience indicates that successful results, especially for patients with MTLE
      HS and lesion-related epilepsies, can be obtained at centers with limited
      resources if the diagnoses and evaluation procedures are performed carefully.

PMID- 10963478
TI  - Epilepsy surgery in developing countries.
AB  - Epilepsy surgery (ES) is a well-accepted treatment for medically intractable
      epilepsy patients in developed countries, but it is highly technology dependent.
      Such technology is not usually available in developing countries. For presurgical
      evaluation, magnetic resonance imaging (MRI) and electroencephalogram recording
      while videotaping the patient have been important. High technology equipment
      will, in conjunction with MRI, identify approximately 70% of ES candidates.
      Introducing ES into developing countries will require determining the candidates
      that are appropriate for the existing medical infrastructure. This article
      reviews ES and its possible introduction into conditions existing in developing
      countries. The authors address (a) the types of patients to be considered for
      resective ES (some patients require a fairly standard series of noninvasive
      studies: others will require extensive invasive studies), (b) ways to determine
      which patients might be appropriate for the existing situation (unilateral mesial
      temporal lobe epilepsy detected with MRI, epilepsy with a circumscribed MRI
      lesion, hemispheric lesions, circumscribed MRI detected neuronal migration, and
      development disorders), (c) surgical procedures (local resection, functional
      hemispherectomy, multiple subpial transections, corpus callosotomy, and
      implantation of a vagal nerve stimulator), (d) special considerations for
      introducing ES into developing countries (medical infrastructure, technology,
      seizure monitoring systems, selective intracarotid/carotid Amytal testing, and
      surgical equipment), and (e) the limitations, realistic expectations, personnel
      requirements, and educational function for selected professionals. Delivery of
      the technology and expertise to perform ES in developing regions of the world is
      a realizable project, but it would be limited by available technology and
      existing medical infrastructure. It should be possible in most areas to train
      local personnel and thereby leave a lasting legacy.

PMID- 10963479
TI  - Continence mechanism based on a modified ileocecal valve.
AB  - PURPOSE: We describe the technique and results of a simply constructed continence
      mechanism for continent urinary diversion to the skin based on the ileocecal
      valve. MATERIALS AND METHODS: During a 3-year period 28 patients underwent
      construction of a continent stoma using the ileocecal valve; 23 patients were
      available for evaluation. The various indications for lower urinary tract
      reconstruction in this patient population included malignancy (4), neurogenic
      bladder (11), and urethral dysfunction (8). The continence mechanism is provided
      by the ileocecal valve, with tapering of the distal ileal segment with an
      absorable stapling device and then securing the catheterizable ileal segment to
      the serosa of the cecum along an opened taenia to provide an additional level of
      continence to the ileocecal valve. RESULTS: Continence was achieved in 83% (19 of
      23) of patients. Two patients required revision and are now dry, and two patients
      have not undergone revision and remain wet. No patients have had problems with
      difficult or traumatic catheterization of the limb or peristomal hernia. One case
      of stomal stenosis was identified and treated with an outpatient revision.
      CONCLUSIONS: This technique for construction of a continence mechanism for a
      continent cutaneous urinary reservoir is simple to create, reliable, and without
      excess morbidity.

PMID- 10963480
TI  - Long-term results of penile vein ligation for erectile dysfunction due to
      cavernovenous disease.
AB  - PURPOSE: We now know that outflow restriction is essential for maintaining a
      rigid erection, which can be achieved after satisfactory smooth muscle
      relaxation. The aim of this study was to assess retrospectively the efficacy of
      penile vein surgical ligation in patients with a follow-up of at least 3 years.
      MATERIALS AND METHODS: Thirty-two men with impotence due to cavernovenous
      occlusive disease underwent penile vein ligation for management of organic
      erectile dysfunction. Cavernovenous occlusive disease was diagnosed by gravity
      cavernosometry. RESULTS: Long-term evaluation revealed sustained potency without
      adjunctive therapy in only 7 patients (21.87%). Twenty-five patients (78.12%) did
      not show any improvement in the erectile mechanism. Associated complications
      included penile shortening in 4 (12.5%), hypoesthesia of the glans area in 2
      (6.25%), and Peyronie's disease in 1 (3.2%). CONCLUSION: Based on these data, we
      conclude that the long-term success of penile vein ligation is poor.

PMID- 10963481
TI  - Burch-Cooper's ligament sling procedure: an augmented incontinence operation.
AB  - PURPOSE: The Burch procedure is used in conjunction with a modified pubovesical
      sling to produce a potentially more durable incontinence operation. This
      augmented incontinence procedure is recommended for use in patients at
      particularly high risk of recurrence of incontinence or in patients with
      intrinsic sphincter deficiency who have concomitant cystocoele (paravaginal
      defect). MATERIALS AND METHODS: A prospective study was initiated to demonstrate
      the efficacy of this combined operative procedure that incorporates two
      established operative techniques. RESULTS: Ten of 13 patients in whom this
      operation was performed are completely continent. They have neither stress nor
      urgency incontinence. They have all resumed active lifestyles. Three patients
      experienced postoperative problems. They had complex presentations and/or
      required multiple operative procedures. Two women continue to have mild urge
      incontinence postoperatively. One of these women has occasional urinary
      retention. The third woman who had a large cystocele, intrinsic sphincter
      deficiency, and rectal prolapse has functional obstruction postoperatively.
      CONCLUSION: Support and stability are developed at the urethrovesical angle by
      means of a combined operative procedure.

PMID- 10963482
TI  - Transrectal ultrasound-guided needle aspiration for prostatic abscesses: an
      alternative to transurethral drainage?
AB  - PURPOSE: Prostatic abscesses traditionally are drained transurethrally. Problems
      of this method include the risk of anesthesia, dissemination of bacteria,
      incomplete drainage of multiloculated or peripheral abscesses, and retrograde
      ejaculation, which may not be acceptable for young patients. Prostatic abscesses
      can be drained under transectal ultrasound (TRUS) guidance. Multiple, peripheral,
      or multiloculated abscesses are visualized. No anesthesia would be required.
      Repeat procedures can be performed easily with minimal morbidity. The risks of
      dissemination and retrograde ejaculation is negligible. MATERIALS AND METHODS: A
      standard TRUS probe and a 21-gauge Chiba needle are inserted through the biopsy
      guide into the abscesses. Five patients underwent the procedure. Four patients
      had a mean follow-up of 18 months. RESULTS: TRUS could visualize the abscess in
      all patients. Aspirate cultures corresponded to the urine culture except in one
      patient with sterile urine. Three had residual disease on repeat TRUS, but only
      two patients required repeat aspiration. All patients recovered and had no
      evidence of disease on follow-up. However, it was an average of 4 months before
      patients could be considered cured according to TRUS findings. Prostate volume
      decreased from a mean of 54 mL on diagnosis to 16 mL on follow-up. There was no
      hospital readmission or morbidity. CONCLUSIONS: TRUS needle aspiration for
      prostatic abscess is a feasible alternative to transurethral drainage. Repeat
      procedures may be required, but all patients recovered. There is minimal
      morbidity associated with the procedure; however, the recovery period may be
      longer.

PMID- 10963483
TI  - Pitfalls in the diagnosis of prostate adenocarcinoma from holmium resection of
      the prostate.
AB  - PURPOSE: Holmium laser resection of the prostate (HoLRP) provides tissue for
      histologic analysis that was not possible using previous coagulative laser
      prostatectomies. It was assumed that these tissue specimens would yield the same
      histologic information as specimens obtained by transurethal resection of the
      prostate and would be adequate for diagnosis of cancer. However, tissue subjected
      to laser treatment may sustain thermal injury, resulting in artifactual change.
      The aim of this study was to define the histologic characteristics of prostate
      tissue after holmium laser prostatectomy and the influence of thermal change on
      diagnosis of malignancy. MATERIALS AND METHODS: All prostate tissue was examined
      after HoLRP. Examination included prostate-specific antigen (PSA) staining and
      immunostaining for high-molecular-weight cytokeratins. Histologic features are
      described. RESULTS: Thermal injury after HoLRP was more extensive than previously
      believed. Artifacts observed under low power consisted of glandular distortion
      and contraction with crowding. Higher magnification revealed clumping of the
      chromatin of the nucleus, resulting in hyperchromasia and irregularity of the
      nucleus and loss of polarity. These changes may be mistaken for malignant change.
      It will be difficult to detect malignancy in areas involved by thermal injury.
      When prostate cancer exists, grading of cancer will be affected by these
      artifacts. Uptake of immunohistochemical staining with PSA and high-molecular
      weight cytokeratins is nonspecific in areas of injury, reducing their usefulness
      in these cases. CONCLUSIONS: Detection of malignancy may be compromised by
      thermal injury occurring after HoLRP. Preliminary preoperative transrectal
      ultrasound-guided biopsies may still be necessary for diagnosis of malignancy.

PMID- 10963484
TI  - Physician responsibility for removal of implants: the case for a computerized
      program for tracking overdue double-J stents.
AB  - PURPOSE: Ureteral stents are used in various modern urologic procedures. Although
      forgotten double-J (JJ) stents are an infrequent problem, they are associated
      with significant medical problems. Encrustation from excessive indwelling time
      increases morbidity and may require extracorporeal shock wave lithotripsy to free
      the coils of the cementing calcerous material. An effective system should be in
      place to ensure timely removal. The previously used "card" system not only is
      difficult to manage but has proved unreliable. We describe a computerized program
      that tracks JJ stents and alerts physicians about stents that need removal.
      MATERIALS AND METHODS: Two hundred eighteen patients who were stented between
      January 1997 and December 1998 were tracked through an integrated computerized
      program. This program keeps a log of all patients who received a JJ stent and
      determines the last date by which it should be removed. Patients are reminded if
      they have not returned for removal of the implant 2 weeks before it is overdue.
      RESULTS: Two hundred twenty-five JJ stents were placed in 218 patients.
      Comparison of data between the periods before and after computer program
      inception showed that the incidence of stents retained longer than their
      expiration time decreased from 12.5% to 1.2% in the first year of the program and
      1.5% in the second year of the program. CONCLUSIONS: Forgotten implants pose a
      significant management dilemma for physicians. Our tracking program significantly
      lowered the incidence of overdue JJ stents from 12.5% to 1.2% and 1.5% in the
      first and second years, of the program respectively (p = .00039). We propose that
      this technically simple program should be in place for all implants placed in
      patients. The problems we encountered in the smooth running of this system could
      be averted by incorporating several recommendations.

PMID- 10963485
TI  - Endourologic management of urinary fistulae.
AB  - PURPOSE: Historically, aggressive surgical exploration of renal fistulae has been
      associated with a 20% nephrectomy rate. We evaluated the role of minimally
      invasive techniques in the management of urinary fistulae. MATERIALS AND METHODS:
      A retrospective review identified 10 renal fistulae in nine patients. Six renal
      cutaneous, two renal-colonic, and two renal-pleural fistulae were referred for
      evaluation and treatment. RESULTS: Five men and four women (mean age 54 years,
      range 32-76) were referred to the University of California, San Francisco Urinary
      Stone Center from 1988 to 1996. Of the six renal-cutaneous fistulae, four were
      spontaneous and two were iatrogenic. The iatrogenic fistulae occurred after an
      open pyelolithotomy (1) and a renal exploration performed after extracorporeal
      shock wave lithotripsy (1). The spontaneous fistulae resulted from obstructing
      calyceal calculi (2), infundibular stenosis (1), and obstructed nephrostomy tube
      (1). The two renal-colonic fistulae resulted from percutaneous nephrolithotomies,
      and the two renal-pleural fistulae developed after renal surgery. Eight of 10
      fistulae resolved with minimally invasive endoscopic techniques and relief of
      urinary obstruction. One nephrectomy was performed for a small nonfunctioning
      kidney after failed open pyelolithotomy. One patient refused all treatment and
      the fistula resolved spontaneously. CONCLUSIONS: Conservative management of both
      spontaneous and iatrogenic renal fistulae is possible by relieving urinary
      obstruction and using minimally invasive endoscopic techniques. Low nephrectomy
      rates can be expected using these methods.

PMID- 10963486
TI  - Bilateral varicocele repair by transscrotal extratunica vaginalis procedure in
      outpatients: a novel technique.
AB  - PURPOSE: A new technique is proposed to repair bilateral varicocele using local
      anesthesia and a single scrotal incision in outpatients. MATERIALS AND METHODS:
      Twenty-three patients with bilateral varicocele underwent bilateral ligation of
      the spermatic veins by median transscrotal procedure. The veins of the anterior
      and posterior pampiniform plexus were ligated and sectioned bilaterally. RESULTS:
      Optical magnification of the area spared the testicular artery. CONCLUSIONS:
      These results and the minimal invasiveness of the method described offer a valid
      alternative to double-access surgery for cases of bilateral varicocele.

PMID- 10963487
TI  - Role of transurethral biopsy sampling of the prostate to diagnose prostate cancer
      in men undergoing surgical intervention for benign prostatic hyperplasia.
AB  - PURPOSE: Newer minimally invasive surgical procedures are being used to treat men
      with significant benign prostatic hyperplasia (BPH). These modalities do not
      allow retrieval of prostate tissue for histologic review. The goal of our study
      was to assess the value of transurethral biopsies in detecting prostate cancer in
      men who would undergo surgical intervention for BPH. MATERIALS AND METHODS:
      Between September 1997 and January 1999, 422 men undergoing transurethral
      resection of the prostate (TURP) had transurethral biopsies obtained before
      completing the TURP. Pathology reports as well as prostate-specific antigen (PSA)
      results were reviewed and analyzed to determine when cancer was present. RESULTS:
      Pathological examination revealed that cancer was found in 53 men (12.5%). The
      transurethral biopsies detected cancer in 32 of 53 (60.4%). No cancers were found
      in the transurethral biopsy specimen only. Of the 21 cancers missed by
      transurethral biopsy, 7 were stage T1b. PSA level >10 ng/mL increased the
      likelihood of finding cancer. CONCLUSIONS: Transurethral biopsy sampling is
      unreliable for detecting prostate cancer in men with clinically significant BPH.
      Significant cancers are missed if transurethral biopsies are used to determine
      the presence of carcinoma before minimally invasive surgical therapy for BPH.

PMID- 10963488
TI  - Are coagulation studies necessary before percutaneous nephrostomy?
AB  - PURPOSE: Performance of coagulation studies for patients undergoing percutaneous
      nephrostomy (PCN) has been advocated by some investigators. We performed a
      retrospective study to assess this practice. MATERIALS AND METHODS: The medical
      records of 180 patients subjected to PCN for various reasons between October 1991
      and July 1998 were reviewed. This represents a subset of patients in whom PCN was
      performed by an experienced interventional radiologist at our institution.
      Patients were excluded if they had a history of active liver disease, hematologic
      or bleeding disorder, current use of heparin or warfarin, or platelet count
      <100,000. The remaining 160 patients were separated into two groups. Group 1
      consisted of 153 patients with a normal prothrombin time (PT) and partial
      thromboplastin time (PTT). Group 2 comprised 7 patients with an abnormal PT or
      PTT. Demographic and laboratory data including PT, PTT, complete blood, and
      platelet counts were analyzed to determine if a hemorrhagic complication could be
      predicted by an abnormal PT or PTT. RESULTS: In group 1 the mean PT was 12.2
      seconds and the mean PTT was 25.0 seconds; in group 2 the mean PT was 13.9
      seconds and the mean PTT was 30.3 seconds. The hemorrhagic complication rates
      were not statistically different between the two patient cohorts (p = .203).
      Demographic and standard laboratory data were not predictive of abnormal
      coagulation parameters. CONCLUSIONS: Screening coagulation studies are
      unnecessary in the standard patient subjected to PCN.

PMID- 10963489
TI  - Re-establishment of dislodged percutaneous nephrostomy tube using a ureteroscope.
AB  - A simple and safe technique for the replacement of a dislodged nephrostomy tube
      using a ureteroscope is presented.

PMID- 10963490
TI  - Endoscopy-assisted Freyer prostatectomy: a safer technique.
AB  - Freyer prostatectomy is infrequently indicated today. One of the blind steps in
      this procedure is when the urethra is disconnected at the prostatic apex. There
      is risk of stress urinary incontinence and damage to the sphincter. We describe a
      safe and a simple endoscopic technique to overcome this difficulty.

PMID- 10963491
TI  - Glandular-tunical stabilization to repair SST deformity of the inflatable penile
      prosthesis.
AB  - Among the complications of penile prosthetic surgery, the SST deformity is
      uncommon. Nonetheless, this functional and cosmetic complication affects patient
      and partner. We describe a modified corrective technique of glandular
      stabilization and repositioning specifically designed for the inflatable penile
      prosthesis. The pericoronal glandular fascia is secured to the tunica albuginea
      by protecting the underlying inflatable cylinder and avoiding tunical plication.
      This technique minimizes the risk of cylinder perforation and penile sensory loss
      and foreshortening.

PMID- 10963492
TI  - Three techniques for simpler, safer, and cost-effective rigid ureteroscopy.
AB  - Postureteroscopy colic, accumulation of irrigant fluid in the bladder, and
      advancement of the ureteroscope through narrow ureters are some of the problems
      commonly encountered during ureteroscopy. Three methods to overcome these
      problems and to make ureteroscopy technically easy, safe and cost-effective are
      described.

PMID- 10963493
TI  - Malignant lymphoma of the kidney presenting with pain and acute renal failure.

PMID- 10963494
TI  - Undetectable prostate-specific antigen response with bicalutamide withdrawal
      phenomenon.
AB  - Several reports have described the antiandrogen withdrawal syndrome with various
      nonsteroidal antiandrogen agents. To our knowledge, there have been no reports
      describing a durable undetectable prostate-specific antigen (PSA) response with
      discontinuation of the antiandrogen agent bicalutamide (Casodex, Zeneca,
      Wilmington, DE, U.S.A.). We report a case in which a decline of serum PSA to
      undetectable levels was achieved with bicalutamide discontinuation.

PMID- 10963495
TI  - Leiomyoma of the female urethra with upper tract dilation and treatment with
      transurethral resection: a case report and literature review.
AB  - Leiomyoma of the female urethra is a rare condition. It is a benign mesenchymal
      tumor that commonly presents with recurrent urinary tract infections and various
      lower urinary tract symptoms. We report a case of urethral leiomyoma and review
      the literature. A 44-year-old woman presented with severe irritative voiding
      symptoms without urinary tract infection and bilateral upper urinary tract
      dilation. Ultrasound and cystoscopy revealed a smooth mass arising from the
      urethra and projecting into the bladder. Transurethral resection of the mass was
      performed and 32 g of tissue was removed. There were no complications and the
      symptoms resolved completely, indicating this to be a safe approach.
      Histopathology showed the tumor to be leiomyoma.

PMID- 10963496
TI  - Inferior vena cava compression due to massive hydronephrosis from bladder outlet
      obstruction.
AB  - A 71-year-old man presented with acute urinary retention due to benign prostatic
      hyperplasia and was found to have computed tomography-documented mechanical
      obstruction of the inferior vena cava (IVC) due to massive hydronephrosis.
      Obstruction of IVC flow promptly resolved after bladder decompression.

PMID- 10963497
TI  - Unilateral nondisseminated actinomycosis of the hydrocele wall: a case report of
      actinomycosis in the urogenital tract.
AB  - Actinomycosis of the urogenital tract is rare and predominantly an infectious
      disease of horses, cattle, swine, and humans. This case report describes isolated
      actinomycosis of the hydrocele wall presenting as an inflamed right-sighted
      hydrocele.

PMID- 10963498
TI  - Management of entrapped ureteral stone baskets.
AB  - Entrapped stone baskets can occur and can lead to significant ureteral injury and
      long-term morbidity. We describe two patients in whom semirigid ureteroscopy was
      used to facilitate safe removal of impacted baskets from the ureter.

PMID- 10963499
TI  - A new approach to orthotopic bladder replacement using the transplanted bowel
      segment.
AB  - PURPOSE: When constructing an orthotopic neobladder, a short colonic mesentery
      may make the operation difficult. We have developed a new technique to
      autotransplant a free segment of intestine into the pelvis to augment the
      bladder. METHODS AND MATERIALS: In this animal feasibility study, we used eight
      female dogs to perform orthotopic bladder replacement using a transplanted bowel
      segment. A segment of bowel was transected and revascularized between the ileal
      artery of the reservoir and the internal iliac artery in the end-to-end fashion.
      RESULTS: Follow-up studies revealed that the bladder autoaugmentation using the
      transplanted bowel segment was functional and free of leakage. CONCLUSIONS: Our
      work in dogs demonstrates that the use of an autotransplanted segment of
      intestine appears to be feasible for augmenting the bladder in those cases where
      mechanical difficulty arises in anastomosing the urinary reservoir to the
      urethra. This procedure merits clinical evaluation in cases that present
      difficulty for completing orthotopic neobladder.

PMID- 10963500
TI  - Low serum insulin-like growth factor 1 (IGF-1): a significant association with
      prostate cancer.
AB  - PURPOSE: Insulin-like growth factor 1 (IGF-1) is an important mitogenic and
      antiapoptotic peptide that affects the proliferation of normal and malignant
      cells. Contradictory reports on the association between serum IGF-1 level and
      prostate cancer have been highlighted in the recent literature. The purpose of
      this study was to investigate the relation between serum levels of IGF-1 and
      prostate cancer. MATERIALS AND METHODS: We analyzed a population of 57 patients
      who underwent radical prostatectomy (RP) for adenocarcinoma. Serum samples were
      collected before RP (T0), 6 months after RP (T6), and from 39 age-matched
      controls. IGF-1 levels were determined by the active IGF-1 Elisa kit (Diagnostic
      Systems Laboratories, Inc.). Parallel samples were evaluated for prostate
      specific antigen (PSA) levels. Data between groups were analyzed using Welch's t
      test and levels before RP and after 6 months were compared by paired t-test.
      RESULTS: The normal mean serum IGF-1 for case patients at T0 (124.6+/-58.2 ng/mL)
      was significantly lower than the control subjects (157.5+/-70.8 ng/mL; p =
      .0192). The normal mean serum IGF-1 for case patients at T0 (124.91+/-58.6 ng/mL)
      also was significantly lower when it was compared with the T6 group (148.49+/
      57.2 ng/mL; p = .0056). No association was found between IGF-1 and PSA blood
      levels, or IGF-1 and patient weight (p = 0.2434). An inverse relation between IGF
      1 levels and age in the normal controls (p = .0041) was observed. CONCLUSION:
      Findings of this study indicate a significant association between low serum
      levels of IGF-1 and prostate cancer.

PMID- 10963501
TI  - Detection of bacterial signal by 16S rRNA polymerase chain reaction in expressed
      prostatic secretions predicts response to antibiotic therapy in men with chronic
      pelvic pain syndrome.
AB  - PURPOSE: Some men with chronic pelvic pain syndrome (CPPS) have evidence of
      bacteria in their prostatic fluid (expressed prostatic secretions [EPS]) detected
      by 16S rRNA techniques. In this study, we correlate presence of bacterial signal
      with response to therapy. MATERIALS AND METHODS: EPS and first voided urine (VB1)
      from 47 men with CPPS were analyzed by polymerase chain reaction (PCR) for
      bacterial signal using universal primers specific for bacterial 16S rRNA. Signal
      was considered positive if found only in the EPS sample, or if at least 10x
      stronger in the EPS than in VB1. All patients were treated with antibiotic
      therapy. RESULTS: Thirty-three patients were category IIIa (nonbacterial
      prostatitis) and 14 were category IIIb (prostatodynia). Seventeen of the 33
      category IIIa patients had positive localizing cultures for gram-positive
      bacteria. However, a positive bacterial signal was detected in 23 EPS samples by
      16S rRNA PCR. This signal was found in 14 of 17 culture-positive patients, 7 of
      16 of the remaining category IIIa patients, and 2 of 14 of category IIIb
      patients. No patient with negative bacterial signal improved with antibiotic
      therapy (negative predictive value 100%). Thirteen patients with positive
      bacterial signal improved with antibiotic therapy. CONCLUSIONS: In men with
      category III chronic prostatitis/CPPS, bacterial signal detected by PCR can help
      predict response to antimicrobial therapy.

PMID- 10963502
TI  - Evaluation and treatment of dystonia.
AB  - BACKGROUND: Dystonia is a neurologic disorder that interferes with normal motor
      control, causing development of bizarre postures and writhing, twisting
      movements. METHODS: The patient database of the Duke Movement Disorders Clinic
      was searched to identify and characterize all cases of dystonia evaluated during
      the 3 1/2 year period between July 1995 and December 1998. RESULTS: Of the 68
      patients identified, 44% had focal dystonia, 10% segmental dystonia, 9%
      hemidystonia, 7% generalized dystonia, 4% multifocal dystonia, 12% psychogenic
      dystonia, and 9% tardive dystonia. The remainder had either paroxysmal or
      pseudodystonia. Twenty-five patients had improvement with botulinum toxin
      injections, 16 with anticholinergics, benzodiazepines and/or baclofen, and 2 with
      tetrabenazine. CONCLUSION: A variety of treatments can give symptomatic benefit
      in dystonia, but appropriate treatment requires proper diagnosis of the
      condition.

PMID- 10963503
TI  - Tumor necrosis factor inactivation in the management of rheumatoid arthritis.
AB  - Biologic agents that target molecules and cells involved in chronic inflammation
      are coming into clinical use for the treatment of rheumatoid arthritis (RA). New
      agents block the action of cytokines, which play a key role in the pathogenesis
      of RA. Among the many cytokines involved in RA, tumor necrosis factor (TNF) is
      believed to be dominant. Two agents for neutralizing TNF are now available. One
      is a recombinant molecule, etanercept, which is derived from a naturally
      occurring TNF antagonist, one of the soluble human TNF receptors. The other,
      infliximab, is a chimeric (human-mouse) monoclonal antibody against human TNF.
      These biologic agents have been shown to relieve symptoms in patients with
      refractory RA. If tolerance of these and other anticipated anticytokine agents
      continues over the long term, treatment for patients with RA will become safer
      and more effective.

PMID- 10963504
TI  - Current management of pelvic fractures.
AB  - Blunt pelvic injuries are becoming more common in this era of high-speed, high
      energy collisions. At least 5% of blunt injuries result in pelvic fracture. With
      mortality rates approaching 55% for severe crush injuries of the pelvis, early
      stabilization and control of bleeding, as well as assessment for other injuries,
      requires a focused, multidisciplinary approach. We discuss early management and
      stabilization of severe pelvic fractures.

PMID- 10963505
TI  - 'Bacilli and bullets': William Osler and the antivaccination movement.
AB  - Public discourse concerning current vaccination recommendations has dramatically
      increased. The current battle is not new, having had a lengthy foreshadowing
      during the 19th and early 20th centuries. Over a 30-year period, a concerted
      effort to limit the use of smallpox vaccine grew at the very time typhoid
      vaccines were being developed and advocated for widespread prevention. As a long
      time advocate for widespread smallpox vaccination and a supporter of the newly
      tested typhoid vaccine, Sir William Osler entered the public debate at the
      beginning of World War I. Osler was asked to address the officers and men in the
      British army on the need for typhoid vaccination. His speech entitled "Bacilli
      and Bullets" outlined the medical reasons for getting inoculated against typhoid.
      Osler's strong support for typhoid vaccination of the British troops was met by
      opposition in Parliament but not by most of the troops. Osler's arguments in
      support of vaccination failed to respond to the concept of "conscientious
      objection," which was central to the antivaccinationists' argument. Similar
      arguments are being propounded by current antivaccination groups.

PMID- 10963506
TI  - Leukocytosis is proportional to HELLP syndrome severity: evidence for an
      inflammatory form of preeclampsia.
AB  - BACKGROUND: We investigated the possibility that HELLP syndrome is in part a
      systemic inflammatory response. METHODS: We evaluated total white blood cell
      (WBC) counts of all patients with severe preeclampsia with and without HELLP
      syndrome admitted to our hospital between 1995 and 1997. Patients were grouped by
      diagnosis and timing of platelet nadir. Analysis of variance and regression
      analysis were used for data analysis. RESULTS: Of 177 patients, 91 had HELLP
      syndrome, and 86 had severe preeclampsia alone. The WBC counts were significantly
      higher in patients with HELLP syndrome (12.5 +/- .442 x 10(9)/L) than in patients
      with severe preeclampsia (10.3 +/- .288 x 10(9)/L). Regression analysis showed
      that platelet counts varied inversely with WBC counts. Also, patients with class
      I HELLP syndrome had significantly higher WBC counts than patients with other
      classes of HELLP syndrome. CONCLUSION: The finding of an association between
      increasing leukocytosis and worsening thrombocytopenia early in the course of
      HELLP syndrome supports the hypothesis that it may represent an inflammatory
      process.

PMID- 10963507
TI  - Domestic violence awareness in a medical school class: 2-year follow-up.
AB  - BACKGROUND: [corrected] Previous studies have examined short-term effectiveness
      of domestic violence instruction. We studied the long-term effectiveness (LTE)
      and long-term retention (LTR) of formal instruction about domestic violence.
      METHODS: A general knowledge survey on domestic violence was given before, 1
      month after, and 2 years after 3 hours of instruction to medical students. Good
      LTE was defined as significant improvement in responses between the first and
      third surveys. Good LTR was defined as lack of a significant decrease in results
      between the second and third surveys. RESULTS: Two years after the instruction,
      104 of 148 (70%) participated. Knowledge of rates of domestic violence against
      women showed neither good LTE nor good LTR. Responses showed good LTE and LTR
      concerning domestic violence incidence among men, ethnic and socioeconomic groups
      being equally represented, victims not being personally responsible for the
      abuse, and physicians not being required to report domestic violence in the
      survey state. Responses showed poor LTR and LTE regarding rates of domestic
      violence in women and abused persons being unable to simply leave their
      situation. CONCLUSIONS: Some improvement in domestic violence awareness was seen
      2 years after instruction. However, some information was not retained. Domestic
      violence instruction should be reemphasized throughout medical school.

PMID- 10963508
TI  - Using DNA fingerprinting to detect transmission of Mycobacterium tuberculosis
      among AIDS patients in two health-care facilities in Puerto Rico.
AB  - BACKGROUND: Fourteen cases of tuberculosis (TB) in Puerto Rico, diagnosed from
      April 1993 to April 1995, had the same DNA fingerprint, documenting disease
      caused by the same strain of Mycobacterium tuberculosis. The 14 cases were
      retrospectively investigated for epidemiologic links. METHODS: Records were
      reviewed and staffs of the TB program, hospital/clinic, and AIDS residential
      facilities were interviewed. RESULTS: Half of the AIDS cases were
      epidemiologically related, providing evidence of TB transmission in an emergency
      department, an AIDS inpatient ward, and an AIDS residential facility. DNA
      fingerprinting allowed detection of M tuberculosis transmission, but contact
      investigators could have documented it sooner. Factors contributing to
      transmission included delayed diagnosis, prolonged infectiousness, inadequate
      discharge planning and infection control procedures, and poor communication
      between health-care facilities. CONCLUSIONS: The numbers of AIDS residential
      facilities are increasing and must understand proper monitoring of TB patients
      and infection control measures that prevent transmissions.

PMID- 10963509
TI  - Basic skin flaps for the general surgeon: a teaching method.
AB  - BACKGROUND: Teaching residents the design and creation of skin flaps is
      challenging because the use of skin flaps is not common enough during the course
      of a typical residency to provide a broad experience base. METHODS: A 12 x 12
      inch board with a 1/8-inch foam rubber covering was designed to provide for the
      creation of four flaps and one Z-plasty. A lecture and practical exercise were
      used to teach basic techniques. Performance was measured by preexamination and
      postexamination, as well as by a resident satisfaction survey. RESULTS: Mean
      scores improved by 45%. The resident survey revealed an average subjective rating
      was 4.7 on a scale of 1 to 5. All residents rated this format superior to
      traditional lecture instruction. Total cost to provide laboratory experience for
      16 residents was $50. Materials can be recovered and reused at a cost of $0.40
      each. CONCLUSIONS: The materials developed provided an effective, inexpensive
      nonbiologic model for teaching preoperative skills.

PMID- 10963510
TI  - Temperature-related deaths in Alabama.
AB  - BACKGROUND: Mortality rates for hyperthermia and hypothermia are higher in
      Alabama than nationally, and Alabama has twice as many hypothermia deaths as
      hyperthermia deaths. These causes of death have not been studied in the
      southeastern United States. We describe the epidemiology of heat- and cold
      related deaths in Alabama. METHODS: We examined state mortality data for the
      years 1987 through 1998 and calculated mortality rates by age, race, and sex.
      RESULTS: Approximately half the hyperthermia-related deaths were among whites,
      and approximately two thirds were among males. Of the hypothermia-related deaths,
      61.5% were among blacks, and approximately three fourths were among males. The
      highest rates of hyperthermia- and hypothermia-related death were among black
      males. Mortality rates increased with age for both causes of death. CONCLUSIONS:
      In Alabama, the elderly and black males are most likely to die of hyperthermia or
      hypothermia. Public health interventions must be directed toward these groups.

PMID- 10963511
TI  - Early diagnostic magnetic resonance imaging in acute disseminated
      encephalomyelitis.
AB  - We report two cases and review the literature concerning the importance of early
      magnetic resonance imaging (MRI) of the brain as a guide for the early diagnosis
      and treatment of acute disseminated encephalomyelitis (ADEM). A nonspecific term,
      ADEM refers to an acute disease that is postinfectious, parainfectious,
      postvaccinal, or of an unknown precipitating factor. Often when there is clinical
      suspicion of ADEM, MRI is not done before significant morbidity and mortality
      occur, despite the existence of adequate treatments. Primary care physicians
      should be aware of the importance of early MRI in ADEM.

PMID- 10963512
TI  - Obstructing giant colonic diverticulum.
AB  - We report the second case of an obstructing true colonic diverticulum. Of the 103
      cases of giant sigmoid diverticulum found in the literature, 13% have been
      reported as true giant sigmoid diverticulum, ie, containing all layers of the
      colonic wall. Our 75-year-old patient had clinical symptoms for only 6 months,
      and endoscopy revealed an almost totally obstructing mass 20 cm from the anus.
      Surgical resection of the sigmoid colon with a primary anastomosis resolved all
      of the patient's obstructive symptoms. A flap-valve mechanism was the cause of
      this true giant colonic diverticulum. Microscopic examination of the diverticulum
      wall revealed all normal layers of colon wall.

PMID- 10963513
TI  - Lipofibromatous hamartoma and related peripheral nerve lesions.
AB  - Three unusual cases of a rare, tumor-like condition, lipofibromatous hamartoma,
      are reported. This lesion is composed of fibrous and fatty tissue that
      infiltrates peripheral nerves, typically on the volar aspect of the upper
      extremities of children and young adults. All three patients had a painless soft
      tissue mass of the wrist and/or hand, which followed nerve distribution, and only
      one patient had neurologic symptoms due to compression. Diagnosis was made by
      open biopsy and histologic examination.

PMID- 10963514
TI  - Disseminated osteoarticular sporotrichosis: treatment in a patient with acquired
      immunodeficiency syndrome.
AB  - We report a case of multiple skin lesions, lymphadenopathy, and osteoarticular
      sporotrichosis in a man infected with human immunodeficiency virus (HIV). He
      subsequently died of tuberculosis after successful treatment for osteoarticular
      sporotrichosis with amphotericin B. We describe the unusual histopathology in
      disseminated sporotrichosis with acquired immunodeficiency syndrome (AIDS) and
      compare it with that seen in patients without AIDS. Although the optimal
      treatment of osteoarticular sporotrichosis in patients with AIDS is unknown, use
      of amphotericin B in our patient appeared successful. Culture and histologic
      stains of all tissues taken at autopsy were negative for sporotrichosis. Recent
      studies of similar cases have shown initial treatment with amphotericin B
      followed by long-term maintenance with itraconazole to be beneficial.

PMID- 10963515
TI  - Allergic reaction to gemfibrozil manifesting as eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis (EGE) is a rare condition of unknown etiology
      characterized by eosinophilic infiltration of the gastrointestinal (GI) tract.
      Previous associations with a drug or food allergy, allergic rhinitis, atopic
      dermatitis, and elevated IgE levels suggest an atopic predisposition in the
      pathogenesis of this disorder. Diagnostic criteria are GI symptoms, eosinophilic
      infiltration proven by biopsy of the GI tract, and absence of parasitic
      infection. We describe a case of EGE manifested as an allergy to gemfibrozil.

PMID- 10963516
TI  - High-dose indium 111In pentetreotide radiotherapy for metastatic atypical
      carcinoid tumor.
AB  - Indium In 111 pentetreotide imaging of neuroendocrine tumors that overexpress
      somatostatin receptors has become standard for localization of these tumors. This
      radioligand is internalized into the cell and can induce receptor-specific
      cytotoxicity by emission of Auger electrons. We hypothesized that high-dose 111In
      pentetreotide could be therapeutic in patients with somatostatin receptor
      expressing tumors. Our 35-year-old patient had atypical carcinoid tumor
      metastatic to cervical, supraclavicular, mediastinal, and mesenteric lymph nodes
      and to the liver and bone. Chemotherapy had stabilized the disease but with
      severe gastrointestinal side effects. After a diagnostic 111In-pentetreotide
      scan, the patient was given eight courses (180 mCi each) of 111In-pentetreotide
      therapy to selectively target somatostatin receptor-expressing tumor cells. The
      disease was stable for approximately 14 months. The patient had two additional
      courses of 111In-pentetreotide therapy (360 mCi each). She died of the disease
      approximately 18 months after initiation of 111In-pentetreotide therapy.

PMID- 10963517
TI  - Idiopathic splenic vein stenosis: a cause of gastric variceal hemorrhage.
AB  - We report the case of a patient with isolated gastric variceal bleeding. Obesity
      precluded the use of noninvasive means for assessing splenic vein patency.
      Splenic vein stenosis was diagnosed by transhepatic portal and splenic venography
      with pressure measurements. A cause for the stenosis could not be found.
      Splenectomy was used as a curative measure.

PMID- 10963518
TI  - Extensive leptomeningeal and intraparenchymatous spinal cord neurosarcoidosis.
AB  - This case of neurosarcoidosis of the spinal cord involved several meningeal areas
      and spinal cord levels. It appears to be the tenth autopsy-documented case of
      neurosarcoidosis of the spinal cord, though the patient had more extensive spinal
      cord disease than has been previously reported.

PMID- 10963519
TI  - Esophageal ulcer caused by cytomegalovirus: resolution during combination
      antiretroviral therapy for acquired immunodeficiency syndrome.
AB  - A 36-year-old man with a 5-year history of untreated human immunodeficiency virus
      (HIV) infection had odynophagia for 14 days. Fifteen days earlier, he had begun
      taking trimethoprim-sulphamethoxazole and combination antiretroviral therapy that
      included lamivudine, zidovudine, and nelfinavir. He had no history of
      opportunistic infection. The CD4 lymphocyte count was 67/microL and HIV-RNA level
      was 359,396 copies/mL. Esophagogastroduodenoscopy revealed a large, well
      circumscribed esophageal ulceration 31 cm from the incisors. Histopathologic
      examination of esophageal biopsy specimens showed cytopathic changes diagnostic
      of cytomegalovirus (CMV). In situ DNA hybridization was positive for CMV. While
      combination antiretroviral therapy was continued, the esophageal symptoms
      resolved within 4 days of endoscopy without specific therapy for CMV. Follow-up
      endoscopy 4 weeks later revealed a normal-appearing esophagus, and the patient
      has remained symptom-free for 10 months.

PMID- 10963520
TI  - Squamous cell carcinoma of the pancreas with cystic degeneration.
AB  - Most nonendocrine pancreatic neoplasms are adenocarcinomas of ductal cell or
      acinar origin. Primary carcinomas of the pancreas with squamous differentiation
      are rare enough to warrant a search for other primary tumors. In the past few
      decades, well-documented individual reports and large series reviews support the
      view that these squamous neoplasms are indeed of pancreatic origin and not
      uncommonly exhibit cystic degeneration. Late manifestation and unfavorable
      prognosis seem to be uniform features. We report a case with many of these
      features.

PMID- 10963521
TI  - Pulmonary infarction after liver transplant and previous hepatopulmonary
      syndrome.
AB  - We describe the case of a 36-year-old woman with previous hepatopulmonary
      syndrome in which a focal pulmonary lesion developed after liver transplantation.
      Thoracoscopic resection showed a pulmonary infarction of the superior segment of
      the right lower lobe. The patient recovered and had no further thrombotic events
      after 2 years of follow-up. The pulmonary vascular changes observed during
      hepatopulmonary syndrome may predispose patients to the development of pulmonary
      infarction.

PMID- 10963522
TI  - Hemangiosarcoma of the spleen: helical computed tomography features.
AB  - Hemangiosarcoma of the spleen is a rare malignant tumor. Prognosis is poor and is
      usually related to splenic rupture. Clinical symptoms include abdominal pain and
      left upper quadrant mass. Many clinical conditions have similar presenting
      symptoms and make diagnosis difficult. However, in this case report, we describe
      characteristic contrast enhancement pattern with spiral CT imaging of
      hemangiosarcoma of the spleen. Such imaging features with the previously
      described clinical symptoms will help in making the diagnosis early. Early
      splenectomy will improve prognosis and survival.

PMID- 10963523
TI  - Contralateral reexpansion pulmonary edema.
AB  - Reexpansion pulmonary edema (RPE) is an unusual complication of thoracentesis.
      Significant morbidity can result, and death is reported in 20% of cases. It is
      typically manifested as edema within a lung that has recently been reexpanded.
      Few reports document contralateral edema formation. We present a case of
      recurrent left-sided pulmonary edema after repeated drainage of a right-sided
      pleural effusion due to hepatic hydrothorax. We believe this is the first
      reported case of recurrence and only the fifth overall case of contralateral RPE.
      We also review the pathophysiology, treatment, and case reports of contralateral
      RPE. Physicians should be aware of the complications of thoracentesis,
      particularly RPE, given the significant morbidity and mortality associated with
      it.

PMID- 10963525
TI  - Another type of medication error: dilution/reconstitution.

PMID- 10963524
TI  - Apophyseal fracture of the greater trochanter.
AB  - Apophyseal fractures about the pelvis and proximal femur are well-described;
      however, these injuries rarely involve the greater trochanter. We report the case
      of a 15-year-old boy of large build who appeared to have all signs and symptoms
      of a left slipped capital femoral epiphysis. No specific inciting event had
      occurred before the hip pain. Radiographs and bone scan of the capital femoral
      epiphysis appeared normal, and follow-up radiographs confirmed an apophyseal
      fracture of the greater trochanter. This case represented a rare occurrence, and
      its interesting manifestation was similar to that of a slipped capital femoral
      epiphysis.

PMID- 10963526
TI  - Why am I here?

PMID- 10963528
TI  - Prognosis of penetrating trauma in elderly patients: a comparison with younger
      patients.
AB  - BACKGROUND: It has previously been shown that elderly patients have a worse
      prognosis than their younger counterparts after sustaining blunt trauma. This is
      due in part to a higher incidence of comorbid conditions as well as less
      physiologic reserve in an elderly population sustaining largely blunt trauma. We
      compared the outcome after penetrating trauma in elderly patients to matched
      "younger" patients to determine whether they had a similarly poor prognosis.
      METHODS: Elderly patients (> or = 65 years) were identified from our trauma
      registry. Sex, mechanism of injury, and Abbreviated Injury Score/Injury Severity
      Score were determined from the registry. Patients presenting with traumatic
      arrest were excluded. The registry was then searched for patients aged 15 to 40
      years with the same sex, mechanism of injury, and Abbreviated Injury Score in
      each region. A chart review was then performed to determine additional details of
      their hospital stay. The two groups were then compared using Student's t test and
      Fisher's exact chi2 test, as appropriate. RESULTS: Eighty-five elderly patients
      (OLD group) were admitted with penetrating trauma between 1983 and 1998. They
      were compared with 85 matched young patients (YOUNG group). Each group included
      66 male and 19 female patients. In each group, gunshot wounds occurred in 45.9%,
      stab wounds in 52.9%, and shotgun wounds in 1.2% of patients. The average Injury
      Severity Score in each group was 5.5 +/- 5.6 (range, 1-29) and the regional
      Abbreviated Injury Scores were likewise equal in both groups. The OLD patients
      had an average hospital stay of 6.9 +/- 9.1 days compared with 4.3 +/- 5.7 days
      in the YOUNG patients (p < 0.05). Twenty-seven OLD patients spent 7.3 +/- 9.2
      days in the intensive care unit compared with 19 YOUNG patients who stayed 3.4 +/
      3.2 days (p < .05). A total of 91 comorbidities were identified in 58 OLD
      patients compared with 18 in 15 YOUNG patients (p < .0001). Eighty-six invasive
      procedures were performed in the OLD group compared with 96 in the YOUNG group (p
      = not significant). Nineteen OLD patients (22.3%) and 15 YOUNG patients (17.6%)
      suffered one or more complications, including death (p = not significant). A
      total of 91% of surviving OLD patients were discharged to home compared with 100%
      of surviving YOUNG patients (p < .01). CONCLUSION: Elderly patients who sustain
      penetrating trauma have more comorbidities than their younger counterparts. This
      may account for their longer hospital stay and lesser ability to be discharged
      home. These patients do not have an increased complication rate and should
      continue to be managed aggressively.

PMID- 10963527
TI  - Blunt splenic injury in adults: Multi-institutional Study of the Eastern
      Association for the Surgery of Trauma.
AB  - BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has
      been applied with increasing frequency. However, the criteria for nonoperative
      management are controversial. The purpose of this multi-institutional study was
      to determine which factors predict successful observation of blunt splenic injury
      in adults. METHODS: A total of 1,488 adults (>15 years of age) with blunt splenic
      injury from 27 trauma centers in 1997 were studied through the Multi
      institutional Trials Committee of the Eastern Association for the Surgery of
      Trauma. Statistical analysis was performed with analysis of variance and extended
      chi2 test. Data are expressed as mean +/- SD; a value of p < 0.05 was considered
      significant. RESULTS: A total of 38.5 % of patients went directly to the
      operating room (group I); 61.5% of patients were admitted with planned
      nonoperative management. Of the patients admitted with planned observation, 10.8%
      failed and required laparotomy; 82.1% of patients with an Injury Severity Score
      (ISS) < 15 and 46.6% of patients with ISS > 15 were successfully observed.
      Frequency of immediate operation correlated with American Association for the
      Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III
      (38.1%), IV (73.7%), and V (94.9%) (p < 0.05). Of patients initially managed
      nonoperatively, the failure rate increased significantly by AAST grade of splenic
      injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p < 0.05). A
      total of 60.9% of the patients failed nonoperative management within 24 hours of
      admission; 8% failed 9 days or later after injury. Laparotomy was ultimately
      performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with
      moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum.
      CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury
      went directly to laparotomy. Ultimately, 54.8% of patients were successfully
      managed nonoperatively; the failure rate of planned observation was 10.8%, with
      60.9% of failures occurring in the first 24 hours. Successful nonoperative
      management was associated with higher blood pressure and hematocrit, and less
      severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and
      quantity of hemoperitoneum.

PMID- 10963529
TI  - Emergent extra-abdominal trauma surgery: is abdominal screening necessary?
AB  - OBJECTIVE: To evaluate the necessity of abdominal screening beyond physical
      examination in awake and alert blunt trauma patients who require emergent extra
      abdominal trauma surgery. METHODS: Data from an urban Level I trauma center was
      reviewed for all blunt trauma patients who underwent extra-abdominal emergency
      procedures during the period from January 1995 through August 1998. Awake and
      alert patients (Glasgow Coma Scale [GCS] score > or = 14) with negative abdominal
      physical examination results who underwent extra-abdominal emergent surgery were
      entered in the study. All patients entered were older than 14 years of age,
      hemodynamically stable, and underwent further abdominal evaluation with computed
      tomographic scan or diagnostic peritoneal lavage after the decision for extra
      abdominal surgical intervention. Emergent surgery occurred within 8 hours of
      admission. Data was collected for results of diagnostic studies, hemodynamic
      status, mechanism of injury, indications for operative intervention, and
      admission blood ethanol (EtOH) levels. RESULTS: A total of 210 patients with an
      average age of 33 years (range, 14-92 years) were entered in the study. The most
      common mechanism of injury was motor vehicle crash (67%). Sixty-six (32%)
      patients presented with EtOH levels > 100 mg/dL; 181 (86%) patients presented
      with a GCS score of 15, and 29 (14%) presented with a GCS score of 14. The
      majority of surgical procedures were orthopedic (86%). Diagnostic peritoneal
      lavage was performed in 55 (26%) patients, and computed tomographic scans were
      obtained in 155 (74%) patients. Three (1.4%) intraperitoneal injuries were
      diagnosed in the study population. Two of the injuries were stable grade 1 liver
      injuries, and missed diaphragmatic injury was diagnosed on postadmission day 1.
      CONCLUSION: Before emergent extra-abdominal trauma surgery, abdominal evaluation
      with physical examination is sufficient to identify surgically significant
      abdominal injury in the awake and alert blunt trauma patient. Screening with
      additional studies does not impact patient outcome.

PMID- 10963530
TI  - Resuscitation of severe chest trauma with four different hemoglobin-based oxygen
      carrying solutions.
AB  - BACKGROUND: The purpose of this study was to test whether polynitroxylation (PN)
      improved the therapeutic profile of hemoglobin-based oxygen-carrying compounds
      (HBOCs) that were unpolymerized (alphaalphaHb) or 70% polymerized (polyHb) in a
      clinically relevant model that combines pulmonary injury and reperfusion. To our
      knowledge, four different HBOC formulations have never been compared in the same
      trauma model. METHODS: Anesthetized, ventilated swine (n = 45) received a
      unilateral lung contusion + 25% hemorrhage. After 60 minutes, 250 mL of either
      PNalphaalphaHb (n = 5), alphaalphaHb (n = 10), PNpolyHb (n = 6), polyHb (n = 5),
      or normal saline (NaCl, n = 10) was administered for 20 minutes, followed by
      standard crystalloid resuscitation for 30 minutes, and supplemental crystalloid
      as required for 6 hours to maintain heart rate <100 beats/min and mean arterial
      pressure >70 mm Hg. RESULTS: Nine of 45 deaths occurred before resuscitation.
      Survival time was 395 minutes with NaCl versus 303 minutes with alphaalphaHb (p =
      0.03) or 238 minutes with PNalphaalphaHb (p = 0.04). With both polymerized HBOCs,
      survival was 480 minutes (polyHb vs. alphaalphaHb, p = 0.005; PNpolyHb vs.
      PNalphaalphaHb, p = 0.006). All HBOCs were pressors (all p < 0.05) and all
      reduced the supplemental fluid required to maintain systemic hemodynamics during
      resuscitation (all p < 0.05). By 90 minutes postresuscitation, cardiac index was
      112% of baseline with NaCl (p < 0.02), but was 78% with alphaalphaHb (p = not
      significant), 63% with PNalphaalphaHb (p < 0.01), 79% with PNpolyHb (p < 0.01),
      and 67% with polyHb p < 0.02). Relative to NaCI, no HBOC altered trauma-induced
      neutrophilia, thrombocytopenia, or the trauma-induced increases in
      bronchoalveolar lavage protein or bronchoalveolar lavage neutrophils. CONCLUSION:
      After resuscitation from chest trauma, we observed the following: (1) all HBOCs
      reduced fluid requirements and increased right and left ventricular afterload
      versus NaCl, which further compromised an already marginal cardiac performance;
      (2) mortality was less with polyHbs relative to alphaalphaHb, but the pressor
      action was unchanged; (3) the pressor action was less with polynitroxylated
      compounds relative to the unmodified HBOC, but this chemical modification had no
      effect on mortality; and (4) the pressor action of HBOCs must be attenuated by
      strategies other than polymerization or polynitroxylation for these compounds to
      be safe, effective resuscitants in humans.

PMID- 10963531
TI  - An artificial neural network as a model for prediction of survival in trauma
      patients: validation for a regional trauma area.
AB  - BACKGROUND: To develop and validate an artificial neural network (ANN) for
      predicting survival of trauma patients based on standard prehospital variables,
      emergency room admission variables, and Injury Severity Score (ISS) using data
      derived from a regional area trauma system, and to compare this model with known
      trauma scoring systems. PATIENT POPULATION: The study was composed of 10,609
      patients admitted to 24 hospitals comprising a seven-county suburban/rural trauma
      region adjacent to a major metropolitan area. The data was generated as part of
      the New York State trauma registry. Study period was from January 1993 through
      December 1996 (1993-1994: 5,168 patients; 1995: 2,768 patients; 1996: 2,673
      patients). METHODS: A standard feed-forward back-propagation neural network was
      developed using Glasgow Coma Scale, systolic blood pressure, heart rate,
      respiratory rate, temperature, hematocrit, age, sex, intubation status, ICD-9-CM
      Injury E-code, and ISS as input variables. The network had a single layer of
      hidden nodes. Initial network development of the model was performed on the 1993
      1994 data. Subsequent models were generated using the 1993, 1994, and 1995 data.
      The model was tested first on the 1995 and then on the 1996 data. The ANN model
      was tested against Trauma and Injury Severity Score (TRISS) and ISS using the
      receiver operator characteristic (ROC) area under the curve [ROC-A(z)], Lemeshow
      Hosmer C-statistic, and calibration curves. RESULTS: The ANN showed good
      clustering of the data, with good separation of nonsurvivors and survivors. The
      ROCA(z) was 0.912 for the ANN, 0.895 for TRISS, and 0.766 for ISS. The ANN
      exceeded TRISS with respect to calibration (Lemeshow-Hosmer C-statistic: 7.4 for
      ANN; 17.1 for TRISS). The prediction of survivors was good for both models. The
      ANN exceeded TRISS in nonsurvivor prediction. CONCLUSION: An ANN developed for
      trauma patients using prehospital, emergency room admission data, and ISS gave
      good prediction of survival. It was accurate and had excellent calibration. This
      study expands our previous results developed at a single Level I trauma center
      and shows that an ANN model for predicting trauma deaths can be applied across
      hospitals with good results

PMID- 10963532
TI  - Weaning injured patients with prolonged pulmonary failure from mechanical
      ventilation in a non-intensive care unit setting.
AB  - BACKGROUND: Injured patients with pulmonary failure often require prolonged
      length of stay in an intensive care unit (ICU), which includes weaning from
      ventilatory support. In the last decade, noninvasive ventilation modes have been
      established as safe and effective. One method for accomplishing this mode of
      ventilation uses a simple bilevel ventilator. Because this ventilator has been
      successfully used in hospital wards, we postulated that bilevel ventilators could
      provide sufficient support during weaning from mechanical ventilation of injured
      patients in a non-ICU setting. METHODS: A retrospective review of trauma patients
      (August 1996-January 1999) undergoing bilevel positive pressure ventilation as
      the final phase of weaning was conducted. Before ward transfer with bilevel
      ventilation, conventionally ventilated ICU patients were changed to bilevel
      ventilation and were required to tolerate this mode for at least 24 hours. All
      patients had a tracheostomy as a secure airway. Outcomes analyzed included ICU
      length of stay, hospital length of stay, duration of mechanical ventilation,
      weaning success, complications, and survival. RESULTS: Fifty-one patients (39
      men, 12 women) with a mean age of 53 received more than 24 hours of bilevel
      positive pressure ventilation. Mean Injury Severity Score was 29, with blunt
      mechanisms of injury occurring in 90%. Chest or spinal cord injuries that
      affected pulmonary mechanics were present in 75% of patients. Ventilator
      associated pneumonia was treated in 43% of patients. Mean ICU length of stay and
      hospital length of stay were 21 and 34 days, respectively. Weaning was successful
      in 89% of patients, whereas 11% were discharged to skilled nursing facilities
      still receiving bilevel positive pressure ventilation. Two patients died, neither
      from a pulmonary nor airway complication. Of the remaining 49 patients, 12 were
      weaned in the ICU and 37 were transferred to the ward with bilevel ventilatory
      support. The average length of ward ventilation was 6.5 +/- 5.4 days (n = 37).
      CONCLUSIONS: Implementation of a program using bilevel ventilation to support the
      terminal phase of weaning seriously injured patients from mechanical ventilation
      was successful. After initiating this mode in the ICU, it was satisfactorily
      continued in standard surgical wards. Because this method enabled the withdrawal
      of ventilatory support in a non-ICU setting, its major advantage was reducing ICU
      length of stay.

PMID- 10963533
TI  - Gut ischemia/reperfusion activates lung macrophages for tumor necrosis factor and
      hydrogen peroxide production.
AB  - BACKGROUND: Gut ischemia followed by reperfusion (I/R) is implicated as a prime
      initiating event in the mechanism of multiple organ failure after trauma and
      hemorrhagic shock. Several lines of evidence indicate that macrophages are
      involved in this prime event. Our purpose was to evaluate hydrogen peroxide
      (H2O2) and tumor necrosis factor (TNF) production and phagocytosis by lung
      macrophages in a gut I/R model of multiple organ failure in rats. METHODS: In the
      experimental group (I/R), Wistar rats (n = 35) were anesthetized and subjected to
      a median laparotomy, and the superior mesenteric artery was clamped for 45
      minutes followed by 60 minutes of reperfusion. In the control group (LAP) (n =
      37), animals underwent sham laparotomy. After the period of reperfusion,
      bronchoalveolar lavage (BAL) was performed and the resulting BAL cells were
      assayed for H2O2 production using the horseradish peroxidase-mediated red phenol
      oxidation method. TNF release was determined using the L929 cells bioassay.
      Zymosan phagocytosis by BAL macrophages was quantitated using phase microscopy.
      RESULTS: H2O2 release in BAL cells of I/R rats (19.90 +/- 7.98 nmol/L/2 x 10(5)
      cells) is statistically higher than in the LAP group (10.92 +/- 5.01 nmol/L per 2
      x 10(5) cells) (p = 0.0155), and the TNF production by BAL cells of the I/R group
      (38.09 +/- 20.79 units per 10(6) cells) was significantly higher than that of LAP
      rats (17.16 +/- 13.35 units per 10(6) cells) (p = 0.0281). Phagocytic activity of
      BAL mac. Macrophages of I/R rats was not statistically different from LAP
      animals. CONCLUSION: These results suggest that BAL macrophage play a role in the
      mechanism of acute lung injury after trauma and hemorrhagic shock.

PMID- 10963534
TI  - Impact of pediatric trauma centers on mortality in a statewide system.
AB  - BACKGROUND: Regional pediatric trauma centers (PTC) were established to optimize
      the care of injured children. However, because of the relative shortage of PTC,
      many injured children continue to be treated at adult trauma centers (ATC). As a
      result, a growing controversy has evolved regarding the impact of PTC and ATC on
      outcome for injured children. METHODS: A retrospective analysis of 13,351 injured
      children entered in the Pennsylvania Trauma Outcome Study between 1993 and 1997
      was conducted. Patients were stratified according to mechanism of injury, injury
      severity, specific organ injury, and type of trauma center: PTC; Level I ATC (ATC
      I); Level II ATC (ATC II); or ATC with added qualifications to treat children
      (ATC AQ). Mortality was the major outcome variable measured. RESULTS: Most
      injured children were treated at a PTC or ATC AQ. The majority of children below
      10 years of age were admitted to PTC. Patients treated at PTC and ATC had similar
      injury severity as determined by median Injury Severity Score, mean Revised
      Trauma Score, and Glasgow Coma Scale. Overall survival was significantly better
      at PTC and ATC AQ compared with ATC I and ATC II. Survival for head, spleen, and
      liver injuries was significantly better at PTC compared with ATC AQ, ATC I, or
      ATC II. Children who sustained moderate or severe head injuries were more likely
      to undergo neurosurgical intervention and have a better outcome when treated at a
      PTC. Despite similar mean Abbreviated Injury Scores for spleen and liver,
      significantly more children underwent surgical exploration (especially
      splenectomy) for spleen and liver injuries at ATC compared with PTC. CONCLUSION:
      Children treated at PTC or ATC AQ have significantly better outcome compared with
      those treated at ATC. Severely injured children (Injury Severity Score > 15) with
      head, spleen, or liver injuries had the best overall outcome when treated at PTC.
      This difference in outcome may be attributable to the approach to operative and
      nonoperative management of head, liver, and spleen injuries at PTC.

PMID- 10963535
TI  - Fibrin sealant foam sprayed directly on liver injuries decreases blood loss in
      resuscitated rats.
AB  - OBJECTIVE: The majority of early trauma deaths are attributable to uncontrolled
      hemorrhage from truncal sites. A hemorrhage-control technique that reduced
      bleeding in the prehospital phase of treatment without requiring manual
      compression may improve the outcome of these patients. We conducted this
      preliminary study to determine whether an expanding fibrin sealant foam (FSF)
      would reduce bleeding from a severe liver injury even during resuscitation.
      METHODS: Rats (n = 31; 291 +/- 5 g; 37.4 +/- 0.3 degrees C; mean +/- SEM),
      underwent a 60 +/- 5% excision of the median hepatic lobe. The animals received
      one of three treatments: (1) FSF, (2) immunoglobulin G placebo foam (IgGF), or
      (3) no treatment. All animals were resuscitated with 40 degrees C lactated
      Ringer's solution at 3.3 mL/ min/kg to a mean arterial pressure of 100 mm Hg.
      Total blood loss, mean arterial pressure, and resuscitation volume were recorded
      for 30 minutes. A qualitative measure of foam coverage and adherence to the cut
      liver edge was recorded. RESULTS: The total blood loss was less (p < 0.01) in the
      FSF group (21.2 +/- 5.0 mL/kg) than in either IgGF (41.4 +/- 4.3 mL/kg) or the no
      treatment group (44.6 +/- 4.7 mL/kg), which did not differ. The resuscitation
      volume was not different. The amount of foam used in the treated groups, 9.1 +/-
      1.0 g in the FSF group and 10.0 +/- 1.0 g in the IgGF group, did not differ.
      Survival for 30 minutes was not different among groups. There was no difference
      in the amount of cut liver covered by either foam, but the clots were more
      adherent (p < 0.05) in the FSF group than in the IgGF group. CONCLUSION: In rats
      with a severe liver injury, spraying fibrin foam directly on the cut liver
      surface decreased blood loss when compared with placebo foam and no treatment.
      This pilot study suggests a future possible treatment for noncompressible truncal
      hemorrhage.

PMID- 10963536
TI  - Burn resuscitation with two doses of 4 mL/kg hypertonic saline dextran provides
      sustained fluid sparing: a 48-hour prospective study in conscious sheep.
AB  - BACKGROUND: The large fluid volumes usually required for burn resuscitation can
      be suppressed for 8 to 12 hours by intravenous infusion of 4 mL x kg(-1)
      hypertonic saline dextran (HSD) 1 hour after burn. We hypothesized that a double
      (8 mL x kg(-1)) dose of HSD or two repeated doses of 4 mL x kg(-1) could enhance
      or prolong the volume sparing. METHODS: We produced a full-thickness flame burn
      covering 40% of the body surface on 18 anesthetized sheep. One hour after the
      burn, the animals were awake and resuscitated with either (1) lactated Ringer's
      solution (LR) only, (2) 8 mL x kg(-1) HSD followed by LR, or (3) 4 mL x kg(-1)
      HSD followed by LR, with a second dose of 4 mL x kg(-1) HSD administered when net
      fluid accumulation increased to 20 mL x kg(-1). For all regimens, infusion rates
      were adjusted to produce a urine output of 1 to 2 mL x kg(-1) x h(-1). RESULTS:
      Animals resuscitated with only LR required fluid volumes identical to that
      predicted by the Parkland formula for the first 12 hours. Infusion of 8 mL x kg(
      1) HSD initially created a net fluid loss (urine output > infused volume),
      followed by a rebound fluid requirement eventually equaling that of animals
      treated with LR only. Animals treated with two separate doses of 4 mL x kg(-1)
      HSD generally did not experience a net fluid loss or a rebound fluid requirement.
      Also in the HSD x 2 group, peak and net fluid accumulation was less than that of
      the other two groups from 18 hours through 48 hours, although the difference was
      not significant. CONCLUSION: An initial 4 mL x kg(-1) dose of HSD reduces fluid
      requirements early after burn, and a second dose administered after an
      appropriate interval may prolong volume sparing through 48 hours. An 8 mL x kg(
      1) continuously infused initial dose was without prolonged fluid sparing effect.
      The volume-sparing effect of HSD is thus dependent on all of the following: dose,
      dosing interval, and infusion rate.

PMID- 10963537
TI  - Sympathectomy for causalgia: experience with military injuries.
AB  - BACKGROUND: Causalgia is a rare disease in civilian practice, and most reports
      regarding causalgia in the literature are from major extended wars. To increase
      awareness of this syndrome, our wartime experience with this disease is
      presented. METHODS: The charts of patients with causalgia referred to two
      university hospitals for treatment from 1985 to 1989 were retrospectively
      studied. Characteristics of the cause, clinical manifestations, and the response
      to therapy were evaluated. RESULTS: Among 1,564 patients with peripheral nerve
      injuries, there were 54 cases (3.4%) of causalgia. All of the patients, except
      five, were injured in battle by high-velocity bullets or missiles. Upper
      extremities were involved in 28 patients (52 %) and lower extremities in 26
      patients (48%). The most common presenting symptoms were as follows: burning
      pain, 100%; wet extremity, 100%; cold extremity, 93%; sensitivity to cold, 89%;
      paresthesia, 78%; and color changes in the extremities, 55%. In 48 patients
      (89%), pain was relieved by sympathetic block (3 patients had permanent cure).
      Six patients had no response to the blocks (11%). Of 45 patients who had
      temporary relief, all underwent sympathectomy. All of these patients had complete
      relief of symptoms in the immediate postoperative period and for follow-up from 1
      to 6 years. CONCLUSION: Causalgia is essentially a war casualty disease. The
      condition is associated with burning pain, hyperesthesia, and symptoms of
      sympathetic overactivity. Sympathectomy is effective and the treatment of choice,
      particularly for patients who respond temporarily to sympathetic blocks.

PMID- 10963538
TI  - A quantitative analysis of head injury using T2*-weighted gradient-echo imaging.
AB  - BACKGROUND: T2*-weighted gradient-echo imaging (T2*-GE) is useful for detecting
      small hemorrhages. METHODS: Thirty-four patients were prospectively examined,
      first by magnetic resonance imaging (1.5 T) and then by T2-weighted fast spin
      echo (T2-FSE) and T2*-GE. Thereafter, the correlations between the T2-FSE or T2*
      GE findings and the clinical or computed tomography findings were analyzed.
      RESULTS: The number of lesions detected by T2*-GE was 14.5 +/- 16.3 (mean +/- SD,
      n = 34), which was significantly (p < 0.001) greater than that detected by T2-FSE
      (5.6 +/- 5.6, n = 34). The findings of T2*-GE correlated positively with both the
      duration of unconsciousness (R2 = 0.74,p < 0.0001) and with Glasgow Outcome Scale
      (R2 = 0.81, p < 0.0001), whereas those of T2-FSE did not show any significant
      correlation. T2*-GE imaging could also detect all areas responsible for focal
      neurologic signs 1 month after in. jury, whereas T2-FSE imaging detected only 22
      of 33 such signs. CONCLUSION: T2*-GE was found to be useful for evaluating the
      clinical symptoms of head injury.

PMID- 10963539
TI  - Effect of immediate weightbearing on plated fractures of the humeral shaft.
AB  - BACKGROUND: This study evaluated the effect of immediate weightbearing on
      fractures of the humeral shaft treated with dynamic compression plates. METHODS:
      Eighty-three fractures met the inclusion criteria. The weightbearing status of
      the humerus was based on associated injuries and not the fracture pattern. There
      were no differences between the weightbearing and nonweightbearing groups in
      patient or fracture demographics. RESULTS: Ninety-four percent of the fractures
      healed after the initial operation. Two in the nonweightbearing group and three
      in the weightbearing group required a second operation to achieve union.
      Alignment did not differ between the two groups. Immediate full weight. bearing
      had no effect on the union or malunion rate. CONCLUSION: When indicated, open
      reduction and internal fixation of the diaphysis of the humerus, followed by
      immediate weightbearing through the involved humerus, is a safe and efficacious
      procedure.

PMID- 10963540
TI  - Detection of occult pneumothoraces on abdominal computed tomographic scans in
      trauma patients.
AB  - BACKGROUND: An unrecognized, or occult, injury is particularly dangerous in
      trauma patients, who often have multiple life-threatening injuries. We sought to
      determine the frequency and quantify the utility of the abdominal computed
      tomographic (CT) scan in detecting occult pneumothoraces. METHODS: Charts of all
      trauma patients diagnosed with a pneumothorax over a 7-year period were
      retrospectively reviewed for findings on admission chest radiograph, abdominal CT
      scan, and other demographic data. RESULTS: A total of 312 charts were reviewed,
      with 230 patients identified as having a pneumothorax at admission. Of the 230
      patients, 126 (54.8%) had an occult pneumothorax identified on abdominal CT scan.
      In these patients, the mean Trauma Score was 14.1 +/- 2.9 and the mean Injury
      Severity Score was 24.1 +/- 11.2. In the group of occult pneumothoraces, 84
      (66.7%) underwent chest tube placement. CONCLUSIONS: Abdominal CT scanning
      provided important information about thoracic trauma often missed on initial
      evaluation in the trauma bay. This information frequently affected the patient's
      clinical management.

PMID- 10963541
TI  - Nomenclature, classification, and signficance of traumatic extrapleural hematoma.
AB  - BACKGROUND: Extrapleural hematoma has been found mostly in single case reports as
      diagnoses with different names. Although huge extrapleural hematoma can cause
      ventilatory and circulatory disturbances and even death, it has received almost
      no attention in the literature. Certain basic and modern facts need to be
      clarified regarding the definition, classification, and significance of
      extrapleural hematoma in the practice of chest trauma. METHODS: A 10-year
      retrospective study was undertaken to analyze the incidence, diagnosis,
      management, morbidity, and mortality of patients with chest trauma and a
      documented extrapleural hematoma. RESULTS: The incidence of traumatic
      extrapleural hematoma was 34 of 477, 7.1%. The incidence of thoracic lesions was
      86 of 34 = 2.5 lesions per patient, whereas the incidence of extrathoracic
      lesions was 30 of 34 = 0.9 lesions per patient. Associated rib fractures were
      found in 30 of 34, 88.2%. More than half of the patients had an associated
      hemothorax. A thoracotomy was used successfully to remove a huge hematoma in one
      patient. CONCLUSION: Extrapleural hematoma has been found to be more common than
      previously reported. Nomenclature and classification are suggested. One of the
      common injuries to the chest, particularly rib fracture, hemothorax, lung
      contusion, or pneumothorax might provide the surgeon with a reliable clinical
      clue that the patient is at inordinate risk to have associated extrapleural
      hematoma. A formal or mini-thoracotomy is the recommended procedure in cases of
      huge hematomas.

PMID- 10963542
TI  - Starch-deferoxamine conjugate inhibits hepatocyte Ca2+ uptake during hemorrhagic
      shock and resuscitation.
AB  - BACKGROUND: This study investigated whether hepatocyte Ca2+ dysregulation after
      hemorrhagic shock and resuscitation could be modulated by the iron chelator
      hydroxyethyl starch-conjugated deferoxamine (HES-DFO). METHODS: In a randomized
      experimental study, anesthetized rats (n = 7) were bled for 60 minutes to
      maintain mean arterial blood pressure at 40 mm Hg. They were then resuscitated
      with 60% of shed blood and threefold the shed-blood volume as lactated Ringer's
      solution, 1 mL of pentastarch solution (hydroxyethyl starch 10%) per mL of shed
      blood, or 1 mL of HES-DFO solution (10%) per mL of shed blood. In isolated
      hepatocytes, the rate of Ca2+ influx (Ca2+ in), total Ca2+ uptake (Ca2+ up), and
      membrane Ca2+ flux (Ca2+ flux) were determined by 45Ca incubation. Reduced or
      oxidized glutathione and malondialdehyde concentrations were assessed
      fluorometrically. RESULTS: Significant increases of hepatocellular Ca2+ in, Ca2+
      up, and Ca2+ flux were observed in rats resuscitated with lactated Ringer's
      solution compared with control groups (p < 0.05). Although hydroxyethyl starch
      decreased Ca2+ in but not Ca2+ up, HES-DFO not only prevented the increase of
      Ca2+ in and Ca2+ up but also inhibited hepatocyte oxidative injury. CONCLUSION:
      Iron-catalyzed oxyradical production and membrane peroxidation seem to alter
      hepatocyte Ca2+ homeostasis after hemorrhagic shock and resuscitation.

PMID- 10963543
TI  - Endotoxin tolerance from lipopolysaccharide pretreatment induces nuclear factor
      kappaB alterations not present in C3H/HeJ mice.
AB  - BACKGROUND: Lipopolysaccharide (LPS) activation of macrophage (MO) cytokine
      secretion requires activation and translocation of nuclear factor-kappaB (NF
      kappaB). Endotoxin tolerance induced in LPS-responsive C3H/HeN MOs by LPS
      pretreatment results in decreased tumor necrosis factor (TNF) secretion and
      altered NF-kappaB activation. C3H/HeJ MOs have a genetic defect that renders them
      tolerant to LPS activation. We hypothesized that the alterations of NF-kappaB
      activation seen with LPS tolerance in HeN MOs would be present in HeJ mice.
      METHODS: MOs from C3H/HeJ and C3H/HeN mice were cultured with +/- 10 ng/mL LPS
      pretreatment for 24 hours and then stimulated with 1 to 1,000 ng/mL LPS.
      Activation of NF-kappaB was assayed by gel shift using a 32P-labeled specific
      oligonucleotide 30 minutes after LPS activation. TNF secretion 6 hours after LPS
      stimulation was measured by bioassay. RESULTS: LPS stimulation activated NF
      kappaB in both HeN and HeJ MOs. We observed decreased NF-kappaB activation and a
      characteristic mobility shift in endotoxin-tolerant MOs from HeN mice that were
      not present in HeJ MOs. In contrast with the results in HeN mice, LPS
      pretreatment did not induce any alterations in NF-kappaB activation in HeJ MOs.
      LPS-stimulated TNF secretion was decreased in HeN MOs after LPS pretreatment.
      There was no change in TNF secretion in HeJ MOs, but, overall, TNF secretion by
      these cells was much less than that seen in HeN cells. CONCLUSION: MOs from
      C3H/HeN mice rendered LPS-tolerant by low-dose LPS pretreatment have alterations
      in activation of NF-kappaB not present in LPS-hyporesponsive C3H/HeJ mice.

PMID- 10963544
TI  - Ileal mucosal response to bacterial toxin challenge.
AB  - BACKGROUND: The cause of postinjury intestinal mucosal barrier disruption remains
      obscure. The present study examines the hypothesis that the bacterial toxin
      formyl-methionyl leucyl phenylalanine (FMLP) plays an initial role in this
      process. METHODS: Mucosal permeability to fluorescein isothiocyanate-labeled
      dextran (4,400 molecular weight) was measured in perfused distal rat ileum with
      and without FMLP. Dextran and myeloperoxidase appearance in the lumenal perfusate
      was assessed in response to surrogates of traumatic stress: ischemia/reperfusion,
      total abdominal irradiation, and total parenteral nutrition. Recovery of FMLP in
      the effluent of static closed and perfused ileal loops was determined by mass
      spectrometry. Release of mast cell mediators in the presence of FMLP was
      determined in ileal everted sacs. RESULTS: Seventy-five percent of FMLP was
      recovered in perfusion effluent in contrast to 5% in closed loops. There was a
      transient increase in ileal permeability in FMLP/perfused, untreated rats, and in
      ischemia/reperfusion and total parenteral nutrition treated rats that was
      recorded with a concomitant increment in myeloperoxidase (inflammatory marker) in
      all experimental models except irradiated rats, which were unresponsive to FMLP.
      FMLP responsiveness was associ. ated with a significant rise in release of
      serotonin (mast cell mediator). CONCLUSION: These results suggest that mast cells
      and other resident inflammatory cells within the gut wall are involved in FMLP
      induced changes in mucosal barrier permeability and raise the possibility that
      under conditions of traumatic stress, proinflammatory mediators within the gut
      wall might be activated by toxic factors in the gut lumen.

PMID- 10963545
TI  - Basal release of endothelin-1 and the influence of the ETB receptor on single
      vessel hydraulic permeability.
AB  - BACKGROUND: Endothelin-1 (ET-1) has a direct permeability decreasing effect on
      the microvasculature. The present study was designed to test the hypothesis that
      this effect is mediated via the endothelin B (ETB) receptor located on the
      microvascular endothelium and to determine whether basal microvascular
      permeability is dependent on constitutive release of ET-1. To isolate the direct
      effect of ET-1, experiments were conducted under conditions in which hydraulic
      and oncotic pressures were controlled. METHODS: Postcapillary venules in the rat
      mesentery were perfused in situ, and paired measurements of hydraulic
      permeability (Lp) were obtained using the modified Landis micro-occlusion method.
      Lp measured after a 15-minute perfusion with the ETB receptor blocker BQ-788 (1
      micromol/L) was compared with measures of Lp obtained after perfusion with a
      combined mixture of BQ-788 and ET-1 (80 pmol/L) (n = 6). In addition, the effect
      of basal endogenous ET-1 was tested by measuring the effects of BQ-788 perfusion
      on Lp (n = 6). RESULTS: Units for Lp are mean +/- SE x 10(-8) cm x s(-1) cm H2O(
      1). ETB receptor blockade prevented any decrease in Lp induced by ET-1 (BQ-788
      alone = 7.9 +/- 0.7; BQ-788 + ET-1 = 8.2 +/- 0.8;p = 0.5). Under basal conditions
      and in the absence of exogenous ET-1, ETB receptor blockade led to a significant
      increase in Lp from 6.8 +/- 0.9 to 9.7 +/- 1.2 (p = 0.001). CONCLUSION: Decreases
      in microvascular permeability in single postcapillary venules after the
      administration of ET-1 are mediated via the ETB receptor. Constitutive release of
      ET-1 from the microvascular endothelium also plays a role in maintaining basal
      levels of permeability. These findings suggest important roles for ET-1 in
      maintaining and modulating microvascular permeability.

PMID- 10963546
TI  - Triolein increases microvascular permeability in isolated perfused rabbit lungs:
      role of neutrophils.
AB  - BACKGROUND: Pathophysiologic mechanisms of the fat embolism syndrome are poorly
      understood. Neutrophils are thought to play a role in the development of many
      forms of acute lung injury. The objective of this study was to examine the role
      of intrapulmonary neutrophils in lung injury resulting from fat infusion.
      METHODS: Triolein (0.08 mL/kg) was infused into isolated rabbit lungs perfused
      with Krebs-Henseleit buffer. Pulmonary arterial pressure was monitored, and
      pulmonary vascular resistance and microvascular permeability (Kf) were measured
      at baseline and 60 minutes after triolein infusion. RESULTS: Triolein produced
      increases in pulmonary arterial pressure, pulmonary vascular resistance, and Kf.
      Neutrophil depletion or inhibition of neutrophil elastase prevented the increase
      in Kf after triolein, and catalase partially blocked this Kf increase.
      CONCLUSION: These results suggest that activated intrapulmonary neutrophils play
      a major role in developing triolein-induced lung injury, intrapulmonary
      neutrophils act chiefly via neutrophil elastase release, and reactive oxygen
      species are involved in the lung injury.

PMID- 10963547
TI  - Effect of nitric oxide synthase inhibitor on experimentally induced burn wounds.
AB  - BACKGROUND: Nitric oxide (NO) may have an important role in the healing of burn
      wounds. This study investigated the effect of NO on experimentally induced burn
      wounds by preventing NO synthesis. METHODS: A total of 40 mice weighing 25 to 30
      g were used in this study. The shaved skin on the back of the mice was immersed
      in 100 degrees C water for 10 seconds to achieve a partial-thickness scald burn.
      The mice were divided into two groups of 20. In group I (control group), 17.5
      mg/kg of serum physiologic (placebo) was injected intraperitoneally two times a
      day for 15 days. In group II (study group), 17.5 mg/kg of aminoguanidine (NO
      synthase inhibitor) was injected intraperitoneally two times a day for 15 days.
      On day 15 of the burn, the animals were killed and the burn areas were
      investigated histologically. Histologic changes such as epithelial proliferation,
      abscess, collagen, and granulation tissue were evaluated. RESULTS: Epithelial
      proliferation, formation of collagen, and granulation tissue with rich
      capillaries observed in the control group were statically significantly higher
      than those observed in the study group (z = -2.022, p < 0.05; z = -2.02, p <
      0.05; and z = -2.022, p < 0.05; respectively). CONCLUSION: We concluded that
      healing of the burn wound is delayed by preventing NO synthesis.

PMID- 10963548
TI  - Vascularized double barrel ribs combined with free serratus anterior muscle
      transfer for homologous restoration of the hindfoot after calcanectomy.

PMID- 10963549
TI  - Bilateral asymmetric traumatic dislocation of the hip joints.

PMID- 10963550
TI  - Penile fracture with complete urethral disruption.

PMID- 10963551
TI  - Synchronized direct current cardioversion of atrial fibrillation after blunt
      chest trauma.

PMID- 10963552
TI  - Left atrial thrombus after emergency left atrial cannulation for cardiopulmonary
      bypass.

PMID- 10963553
TI  - Unsuspected child abuse revealed by delayed presentation of periportal tracking
      and myoglobinuria.

PMID- 10963554
TI  - Sexually acquired vascular injuries of the penis: a review.

PMID- 10963555
TI  - Traumatic arteriovenous fistula of the superficial temporal artery.

PMID- 10963556
TI  - Treatment of supracondylar fractures of the femur.

PMID- 10963557
TI  - Intraarticular dislocation of the patella.

PMID- 10963558
TI  - The trials of xenotransplantation.

PMID- 10963559
TI  - Seeing the wood for the trees.

PMID- 10963560
TI  - German scientists left in the cold as Berlin rejects rescue plan

PMID- 10963561
TI  - Roslin backs off pig organ work.

PMID- 10963562
TI  - German government takes a narrow view of gene patents.

PMID- 10963563
TI  - Deal on reprints could mean royalties for scientists.

PMID- 10963564
TI  - Japan seeks to unify ethics rules on genomics research.

PMID- 10963566
TI  - NASA pins hopes on bigger, costlier mission to Mars

PMID- 10963565
TI  - The sky's the limit as radio telescope array is approved

PMID- 10963567
TI  - Science champion joins US election race.

PMID- 10963568
TI  - Chemist tipped for top UK science post

PMID- 10963569
TI  - US dispute over definition of animal distress.

PMID- 10963570
TI  - New fronts in an old war.

PMID- 10963571
TI  - Though HIV is the main cause of AIDS, other factors play a role.

PMID- 10963572
TI  - Responsible aquaculture can aid food problems.

PMID- 10963573
TI  - Will we ever know what the Chinese knew?

PMID- 10963575
TI  - Worlds of IIF

PMID- 10963574
TI  - Powerful reactions

PMID- 10963576
TI  - Crop strength through diversity.

PMID- 10963577
TI  - Artificial noses. Picture the smell.

PMID- 10963578
TI  - Lipid lunch for persistent pathogen.

PMID- 10963579
TI  - Feedback on Gaia.

PMID- 10963581
TI  - Organic materials. From insulator to superconductor

PMID- 10963580
TI  - Neurobiology. The shaky trace.

PMID- 10963582
TI  - Taking up iodide in breast tissue.

PMID- 10963583
TI  - Ice sheets by volume

PMID- 10963584
TI  - Attention is fast but volition is slow.

PMID- 10963585
TI  - Biogeography. A marine Wallace's line?

PMID- 10963586
TI  - Tokaimura accident. Neutron dose estimates from 5-yen coins.

PMID- 10963587
TI  - Atmospheric carbon dioxide concentrations over the past 60 million years.
AB  - Knowledge of the evolution of atmospheric carbon dioxide concentrations
      throughout the Earth's history is important for a reconstruction of the links
      between climate and radiative forcing of the Earth's surface temperatures.
      Although atmospheric carbon dioxide concentrations in the early Cenozoic era
      (about 60 Myr ago) are widely believed to have been higher than at present, there
      is disagreement regarding the exact carbon dioxide levels, the timing of the
      decline and the mechanisms that are most important for the control of CO2
      concentrations over geological timescales. Here we use the boron-isotope ratios
      of ancient planktonic foraminifer shells to estimate the pH of surface-layer sea
      water throughout the past 60 million years, which can be used to reconstruct
      atmospheric CO2 concentrations. We estimate CO2 concentrations of more than 2,000
      p.p.m. for the late Palaeocene and earliest Eocene periods (from about 60 to 52
      Myr ago), and find an erratic decline between 55 and 40 Myr ago that may have
      been caused by reduced CO2 outgassing from ocean ridges, volcanoes and
      metamorphic belts and increased carbon burial. Since the early Miocene (about 24
      Myr ago), atmospheric CO2 concentrations appear to have remained below 500 p.p.m.
      and were more stable than before, although transient intervals of CO2 reduction
      may have occurred during periods of rapid cooling approximately 15 and 3 Myr ago.

PMID- 10963588
TI  - Deep and stable interferometric nulling of broadband light with implications for
      observing planets around nearby stars
AB  - The number of indirectly detected planetary systems around nearby stars has grown
      tremendously since their initial discovery five years ago. But the direct
      observation of light reflected from these systems remains a formidable task,
      because of the high contrast ratios between them and their parent stars, and
      because of the tiny angular separations. Theoretically, these difficulties can be
      overcome by using a dual-aperture stellar interferometer in which the starlight
      is cancelled, or 'nulled' by broadband destructive interference, leaving the
      planet's light visible. Although the basic requirement of equal and oppositely
      directed electric fields is easy to state, an experimental demonstration of deep
      broadband nulling has been lacking, owing to difficulties engendered by the needs
      for extreme symmetry and stability, and low dispersion in the optical system.
      Here we report the deep (10(-4)) and stable nulling of broadband (18% bandwidth)
      thermal light. These results validate the physical principles underlying future
      planet-searching interferometers, and our laboratory instrument will serve as a
      prototype for the nulling instrument to be implemented on the Keck interferometer
      in 2001.

PMID- 10963589
TI  - Superconductivity in molecular crystals induced by charge injection.
AB  - Progress in the field of superconductivity is often linked to the discovery of
      new classes of materials, with the layered copper oxides being a particularly
      impressive example. The superconductors known today include a wide spectrum of
      materials, ranging in complexity from simple elemental metals, to alloys and
      binary compounds of metals, to multi-component compounds of metals and chalcogens
      or metalloids, doped fullerenes and organic charge-transfer salts. Here we
      present a new class of superconductors: insulating organic molecular crystals
      that are made metallic through charge injection. The first examples are
      pentacene, tetracene and anthracene, the last having the highest transition
      temperature, at 4 K. We anticipate that many other organic molecular crystals can
      also be made superconducting by this method, which will lead to surprising
      findings in the vast composition space of molecular crystals.

PMID- 10963590
TI  - Room-temperature electronic phase transitions in the continuous phase diagrams of
      perovskite manganites
AB  - Highly correlated electronic systems--such as transition-metal oxides that are
      doped Mott insulators--are complex systems which exhibit puzzling phenomena,
      including high-temperature superconductivity and colossal magnetoresistivity.
      Recent studies suggest that in such systems collective electronic phenomena are
      important, arising from long-range Coulomb interactions and magnetic effects. The
      qualitative behaviour of these systems is strongly dependent on charge filling
      (the level of doping) and the lattice constant. Here we report a time-efficient
      and systematic experimental approach for studying the phase diagrams of condensed
      matter systems. It involves the continuous mapping of the physical properties of
      epitaxial thin films of perovskite manganites (a class of doped Mott insulator)
      as their composition is varied. We discover evidence that suggests the presence
      of phase boundaries of electronic origin at room temperature.

PMID- 10963591
TI  - Stress transmission through a model system of cohesionless elastic grains
AB  - Understanding the mechanical properties of granular materials is important for
      applications in civil and chemical engineering, geophysical sciences and the food
      industry, as well as for the control or prevention of avalanches and landslides.
      Unlike continuous media, granular materials lack cohesion, and cannot resist
      tensile stresses. Current descriptions of the mechanical properties of
      collections of cohesionless grains have relied either on elasto-plastic models
      classically used in civil engineering, or on a recent model involving hyperbolic
      equations. The former models suggest that collections of elastic grains submitted
      to a compressive load will behave elastically. Here we present the results of an
      experiment on a two-dimensional model system--made of discrete square cells
      submitted to a point load--in which the region in which the stress is confined is
      photoelastically visualized as a parabola. These results, which can be
      interpreted within a statistical framework, demonstrate that the collective
      response of the pile contradicts the standard elastic predictions and supports a
      diffusive description of stress transmission. We expect that these findings will
      be applicable to problems in soil mechanics, such as the behaviour of
      cohesionless soils or sand piles.

PMID- 10963592
TI  - A colorimetric sensor array for odour visualization.
AB  - Array-based vapour-sensing devices are used to detect and differentiate between
      chemically diverse analytes. These systems--based on cross-responsive sensor
      elements--aim to mimic the mammalian olfactory system by producing composite
      responses unique to each odorant. Previous work has concentrated on a variety of
      non-specific chemical interactions to detect non-coordinating organic vapours.
      But the most odiferous, toxic compounds often bind readily to metal ions. Here we
      report a simple optical chemical sensing method that utilizes the colour change
      induced in an array of metalloporphyrin dyes upon ligand binding while minimizing
      the need for extensive signal transduction hardware. The chemoselective response
      of a library of immobilized vapour-sensing metalloporphyrin dyes permits the
      visual identification of a wide range of ligating (alcohols, amines, ethers,
      phosphines, phosphites, thioethers and thiols) and even weakly ligating (arenes,
      halocarbons and ketones) vapours. Water vapour does not affect the performance of
      the device, which shows a good linear response to single analytes, and
      interpretable responses to analyte mixtures. Unique colour fingerprints can be
      obtained at analyte concentrations below 2 parts per million, and responses to
      below 100 parts per billion have been observed. We expect that this type of
      sensing array will be of practical importance for general-purpose vapour
      dosimeters and analyte-specific detectors (for insecticides, drugs or
      neurotoxins, for example).

PMID- 10963593
TI  - Timing of the Last Glacial Maximum from observed sea-level minima
AB  - During the Last Glacial Maximum, ice sheets covered large areas in northern
      latitudes and global temperatures were significantly lower than today. But few
      direct estimates exist of the volume of the ice sheets, or the timing and rates
      of change during their advance and retreat. Here we analyse four distinct
      sediment facies in the shallow, tectonically stable Bonaparte Gulf, Australia-
      each of which is characteristic of a distinct range in sea level--to estimate the
      maximum volume of land-based ice during the last glaciation and the timing of the
      initial melting phase. We use faunal assemblages and preservation status of the
      sediments to distinguish open marine, shallow marine, marginal marine and
      brackish conditions, and estimate the timing and the mass of the ice sheets using
      radiocarbon dating and glacio-hydro-isostatic modelling. Our results indicate
      that from at least 22,000 to 19,000 (calendar) years before present, land-based
      ice volume was at its maximum, exceeding today's grounded ice sheets by 52.5 x
      10(6) km. A rapid decrease in ice volume by about 10% within a few hundred years
      terminated the Last Glacial Maximum at 19,000 +/- 250 years.

PMID- 10963594
TI  - Cursoriality in bipedal archosaurs.
AB  - Modern birds have markedly foreshortened tails and their body mass is centred
      anteriorly, near the wings. To provide stability during powered flight, the avian
      centre of mass is far from the pelvis, which poses potential balance problems for
      cursorial birds. To compensate, avians adapted to running maintain the femur
      subhorizontally, with its distal end situated anteriorly, close to the animal's
      centre of mass; stride generation stems largely from parasagittal rotation of the
      lower leg about the knee joint. In contrast, bipedal dinosaurs had a centre of
      mass near the hip joint and rotated the entire hindlimb during stride generation.
      Here we show that these contrasting styles of cursoriality are tightly linked to
      longer relative total hindlimb length in cursorial birds than in bipedal
      dinosaurs. Surprisingly, Caudipteryx, described as a theropod dinosaur, possessed
      an anterior centre of mass and hindlimb proportions resembling those of cursorial
      birds. Accordingly, Caudipteryx probably used a running mechanism more similar to
      that of modern cursorial birds than to that of all other bipedal dinosaurs. These
      observations provide valuable clues about cursoriality in Caudipteryx, but may
      also have implications for interpreting the locomotory status of its ancestors.

PMID- 10963595
TI  - Genetic diversity and disease control in rice.
AB  - Crop heterogeneity is a possible solution to the vulnerability of monocultured
      crops to disease. Both theory and observation indicate that genetic heterogeneity
      provides greater disease suppression when used over large areas, though
      experimental data are lacking. Here we report a unique cooperation among farmers,
      researchers and extension personnel in Yunnan Province, China--genetically
      diversified rice crops were planted in all the rice fields in five townships in
      1998 and ten townships in 1999. Control plots of monocultured crops allowed us to
      calculate the effect of diversity on the severity of rice blast, the major
      disease of rice. Disease-susceptible rice varieties planted in mixtures with
      resistant varieties had 89% greater yield and blast was 94% less severe than when
      they were grown in monoculture. The experiment was so successful that fungicidal
      sprays were no longer applied by the end of the two-year programme. Our results
      support the view that intraspecific crop diversification provides an ecological
      approach to disease control that can be highly effective over a large area and
      contribute to the sustainability of crop production.

PMID- 10963596
TI  - Fear memories require protein synthesis in the amygdala for reconsolidation after
      retrieval.
AB  - 'New' memories are initially labile and sensitive to disruption before being
      consolidated into stable long-term memories. Much evidence indicates that this
      consolidation involves the synthesis of new proteins in neurons. The lateral and
      basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in
      fear learning. Infusion of the protein synthesis inhibitor anisomycin into the
      LBA shortly after training prevents consolidation of fear memories. Here we show
      that consolidated fear memories, when reactivated during retrieval, return to a
      labile state in which infusion of anisomycin shortly after memory reactivation
      produces amnesia on later tests, regardless of whether reactivation was performed
      1 or 14 days after conditioning. The same treatment with anisomycin, in the
      absence of memory reactivation, left memory intact. Consistent with a time
      limited role for protein synthesis production in consolidation, delay of the
      infusion until six hours after memory reactivation produced no amnesia. Our data
      show that consolidated fear memories, when reactivated, return to a labile state
      that requires de novo protein synthesis for reconsolidation. These findings are
      not predicted by traditional theories of memory consolidation.

PMID- 10963597
TI  - Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel
      cortex.
AB  - In the rodent primary somatosensory cortex, the configuration of whiskers and
      sinus hairs on the snout and of receptor-dense zones on the paws is
      topographically represented as discrete modules of layer IV granule cells
      (barrels) and thalamocortical afferent terminals. The role of neural activity,
      particularly activity mediated by NMDARs (N-methyl-D-aspartate receptors), in
      patterning of the somatosensory cortex has been a subject of debate. We have
      generated mice in which deletion of the NMDAR1 (NR1) gene is restricted to
      excitatory cortical neurons, and here we show that sensory periphery-related
      patterns develop normally in the brainstem and thalamic somatosensory relay
      stations of these mice. In the somatosensory cortex, thalamocortical afferents
      corresponding to large whiskers form patterns and display critical period
      plasticity, but their patterning is not as distinct as that seen in the cortex of
      normal mice. Other thalamocortical patterns corresponding to sinus hairs and
      digits are mostly absent. The cellular aggregates known as barrels and barrel
      boundaries do not develop even at sites where thalamocortical afferents cluster.
      Our findings indicate that cortical NMDARs are essential for the aggregation of
      layer IV cells into barrels and for development of the full complement of
      thalamocortical patterns.

PMID- 10963598
TI  - Calcium channels activated by hydrogen peroxide mediate abscisic acid signalling
      in guard cells.
AB  - Drought is a major threat to agricultural production. Plants synthesize the
      hormone abscisic acid (ABA) in response to drought, triggering a signalling
      cascade in guard cells that results in stomatal closure, thus reducing water
      loss. ABA triggers an increase in cytosolic calcium in guard cells ([Ca2+]cyt)
      that has been proposed to include Ca2+ influx across the plasma membrane.
      However, direct recordings of Ca2+ currents have been limited and the upstream
      activation mechanisms of plasma membrane Ca2+ channels remain unknown. Here we
      report activation of Ca2+-permeable channels in the plasma membrane of
      Arabidopsis guard cells by hydrogen peroxide. The H2O2-activated Ca2+ channels
      mediate both influx of Ca2+ in protoplasts and increases in [Ca2+]cyt in intact
      guard cells. ABA induces the production of H2O2 in guard cells. If H2O2
      production is blocked, ABA-induced closure of stomata is inhibited. Moreover,
      activation of Ca2+ channels by H2O2 and ABA- and H2O2-induced stomatal closing
      are disrupted in the recessive ABA-insensitive mutant gca2. These data indicate
      that ABA-induced H2O2 production and the H2O2-activated Ca2+ channels are
      important mechanisms for ABA-induced stomatal closing.

PMID- 10963599
TI  - Persistence of Mycobacterium tuberculosis in macrophages and mice requires the
      glyoxylate shunt enzyme isocitrate lyase.
AB  - Mycobacterium tuberculosis claims more human lives each year than any other
      bacterial pathogen. Infection is maintained in spite of acquired immunity and
      resists eradication by antimicrobials. Despite an urgent need for new therapies
      targeting persistent bacteria, our knowledge of bacterial metabolism throughout
      the course of infection remains rudimentary. Here we report that persistence of
      M. tuberculosis in mice is facilitated by isocitrate lyase (ICL), an enzyme
      essential for the metabolism of fatty acids. Disruption of the icl gene
      attenuated bacterial persistence and virulence in immune-competent mice without
      affecting bacterial growth during the acute phase of infection. A link between
      the requirement for ICL and the immune status of the host was established by the
      restored virulence of delta icl bacteria in interferon-gamma knockout mice. This
      link was apparent at the level of the infected macrophage: Activation of infected
      macrophages increased expression of ICL, and the delta icl mutant was markedly
      attenuated for survival in activated but not resting macrophages. These data
      suggest that the metabolism of M. tuberculosis in vivo is profoundly influenced
      by the host response to infection, an observation with important implications for
      the treatment of chronic tuberculosis.

PMID- 10963600
TI  - Progression of autoimmune diabetes driven by avidity maturation of a T-cell
      population.
AB  - For unknown reasons, autoimmune diseases such as type 1 diabetes develop after
      prolonged periods of inflammation of mononuclear cells in target tissues. Here we
      show that progression of pancreatic islet inflammation to overt diabetes in
      nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a
      prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the
      CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP
      and NRP-A7) in the context of H-2Kd class I molecules of the major
      histocompatibility complex (MHC). As pre-diabetic NOD mice age, their islet
      associated CD8+ T lymphocytes contain increasing numbers of NRP-A7-reactive
      cells, and these cells bind NRP-A7/H-2Kd tetramers with increased specificity,
      increased avidity and longer half-lives. Repeated treatment of pre-diabetic NOD
      mice with soluble NRP-A7 peptide blunts the avidity maturation of the NRP-A7
      reactive CD8+ T-cell population by selectively deleting those clonotypes
      expressing T-cell receptors with the highest affinity and lowest dissociation
      rates for peptide-MHC binding. This inhibits the local production of T cells that
      are cytotoxic to beta cells, and halts the progression from severe insulitis to
      diabetes. We conclude that avidity maturation of pathogenic T-cell populations
      may be the key event in the progression of benign inflammation to overt disease
      in autoimmunity.

PMID- 10963601
TI  - The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells.
AB  - Syk is a protein tyrosine kinase that is widely expressed in haematopoietic
      cells. It is involved in coupling activated immunoreceptors to downstream
      signalling events that mediate diverse cellular responses including
      proliferation, differentiation and phagocytosis. Syk expression has been reported
      in cell lines of epithelial origin, but its function in these cells remains
      unknown. Here we show that Syk is commonly expressed in normal human breast
      tissue, benign breast lesions and low-tumorigenic breast cancer cell lines. Syk
      messenger RNA and protein, however, are low or undetectable in invasive breast
      carcinoma tissue and cell lines. Transfection of wild-type Syk into a Syk
      negative breast cancer cell line markedly inhibited its tumour growth and
      metastasis formation in athymic mice. Conversely, overexpression of a kinase
      deficient Syk in a Syk-positive breast cancer cell line significantly increased
      its tumour incidence and growth. Suppression of tumour growth by the
      reintroduction of Syk appeared to be the result of aberrant mitosis and
      cytokinesis. We propose that Syk is a potent modulator of epithelial cell growth
      and a potential tumour suppressor in human breast carcinomas.

PMID- 10963602
TI  - Molecular portraits of human breast tumours.
AB  - Human breast tumours are diverse in their natural history and in their
      responsiveness to treatments. Variation in transcriptional programs accounts for
      much of the biological diversity of human cells and tumours. In each cell, signal
      transduction and regulatory systems transduce information from the cell's
      identity to its environmental status, thereby controlling the level of expression
      of every gene in the genome. Here we have characterized variation in gene
      expression patterns in a set of 65 surgical specimens of human breast tumours
      from 42 different individuals, using complementary DNA microarrays representing
      8,102 human genes. These patterns provided a distinctive molecular portrait of
      each tumour. Twenty of the tumours were sampled twice, before and after a 16-week
      course of doxorubicin chemotherapy, and two tumours were paired with a lymph node
      metastasis from the same patient. Gene expression patterns in two tumour samples
      from the same individual were almost always more similar to each other than
      either was to any other sample. Sets of co-expressed genes were identified for
      which variation in messenger RNA levels could be related to specific features of
      physiological variation. The tumours could be classified into subtypes
      distinguished by pervasive differences in their gene expression patterns.

PMID- 10963603
TI  - Potential for biomolecular imaging with femtosecond X-ray pulses.
AB  - Sample damage by X-rays and other radiation limits the resolution of structural
      studies on non-repetitive and non-reproducible structures such as individual
      biomolecules or cells. Cooling can slow sample deterioration, but cannot
      eliminate damage-induced sample movement during the time needed for conventional
      measurements. Analyses of the dynamics of damage formation suggest that the
      conventional damage barrier (about 200 X-ray photons per A2 with X-rays of 12 keV
      energy or 1 A wavelength) may be extended at very high dose rates and very short
      exposure times. Here we have used computer simulations to investigate the
      structural information that can be recovered from the scattering of intense
      femtosecond X-ray pulses by single protein molecules and small assemblies.
      Estimations of radiation damage as a function of photon energy, pulse length,
      integrated pulse intensity and sample size show that experiments using very high
      X-ray dose rates and ultrashort exposures may provide useful structural
      information before radiation damage destroys the sample. We predict that such
      ultrashort, high-intensity X-ray pulses from free-electron lasers that are
      currently under development, in combination with container-free sample handling
      methods based on spraying techniques, will provide a new approach to structural
      determinations with X-rays.

PMID- 10963604
TI  - On the particularity of pathogens.
AB  - In the elemental struggle between pathogenic microbes and the immune system of
      the host, each strives for a unique advantage and thus each exploits its own
      unique particularities in pathogenesis and protection. And each presumably
      selects for the diversity that generally characterizes the wide range of
      successful host-pathogen interactions.

PMID- 10963605
TI  - Changing patterns of infectious disease.
AB  - Despite a century of often successful prevention and control efforts, infectious
      diseases remain an important global problem in public health, causing over 13
      million deaths each year. Changes in society, technology and the microorganisms
      themselves are contributing to the emergence of new diseases, the re-emergence of
      diseases once controlled, and to the development of antimicrobial resistance. Two
      areas of special concern in the twenty-first century are food-borne disease and
      antimicrobial resistance. The effective control of infectious diseases in the new
      millennium will require effective public health infrastructures that will rapidly
      recognize and respond to them and will prevent emerging problems.

PMID- 10963606
TI  - Pathogenic strategies of enteric bacteria.
AB  - Enteric bacteria use a limited array of macromolecular systems to implement
      diverse pathogenic strategies. The cellular targets of several enteric virulence
      factors have recently been identified. The themes that have emerged from these
      studies include the exploitation of molecules that regulate the actin
      cytoskeleton and the activation of apoptotic pathways to serve the pathogen.

PMID- 10963607
TI  - Molecular mechanisms that confer antibacterial drug resistance.
AB  - Antibiotics--compounds that are literally 'against life'--are typically
      antibacterial drugs, interfering with some structure or process that is essential
      to bacterial growth or survival without harm to the eukaryotic host harbouring
      the infecting bacteria. We live in an era when antibiotic resistance has spread
      at an alarming rate and when dire predictions concerning the lack of effective
      antibacterial drugs occur with increasing frequency. In this context it is
      apposite to ask a few simple questions about these life-saving molecules. What
      are antibiotics? Where do they come from? How do they work? Why do they stop
      being effective? How do we find new antibiotics? And can we slow down the
      development of antibiotic-resistant superbugs?

PMID- 10963608
TI  - Toll-like receptors in the induction of the innate immune response.
AB  - The innate immune response is the first line of defence against infectious
      disease. The principal challenge for the host is to detect the pathogen and mount
      a rapid defensive response. A group of proteins that comprise the Toll or Toll
      like family of receptors perform this role in vertebrate and invertebrate
      organisms. This reflects a remarkable conservation of function and it is
      therefore not surprising that studies of the mechanism by which they act has
      revealed new and important insights into host defence.

PMID- 10963610
TI  - Vaccines against intracellular infections requiring cellular immunity.
AB  - Vaccines against a variety of infectious diseases represent one of the great
      triumphs of medicine. The immune correlates of protection induced by most current
      vaccines seem to be mediated by long-lived humoral immune responses. By contrast,
      there are no currently available vaccines that are uniformly effective for
      diseases such as HIV, malaria and tuberculosis, in which the cellular immune
      response might be crucial in mediating protection. Here we examine the mechanisms
      by which long-lived cellular immune responses are generated and maintained in
      vivo. We then discuss current approaches for vaccination against diseases in
      which cellular immune responses are important for protection.

PMID- 10963609
TI  - CD1-restricted T-cell responses and microbial infection.
AB  - CD1, a conserved family of major histocompatibility (MHC)-like glycoproteins in
      mammals, specializes in capturing lipid rather than peptide antigen for
      presentation to T lymphocytes. The principles and mechanisms of this newly
      discovered immune strategy differ markedly from those governing classical MHC
      peptide presentation. They might be exploited for the design of new lipid-based
      microbial vaccines and adjuvants.

PMID- 10963611
TI  - Microbial genome sequencing.
AB  - Complete genome sequences of 30 microbial species have been determined during the
      past five years, and work in progress indicates that the complete sequences of
      more than 100 further microbial species will be available in the next two to four
      years. These results have revealed a tremendous amount of information on the
      physiology and evolution of microbial species, and should provide novel
      approaches to the diagnosis and treatment of infectious disease.

PMID- 10963612
TI  - 'Quiet revolution' in chemistry could revive public and private sectors.

PMID- 10963613
TI  - European industry turns to the academics to secure its future.

PMID- 10963614
TI  - Emerging fields of basic chemistry in Europe.

PMID- 10963615
TI  - Mergers and acquisitions rock UK chemical industry infrastructure.

PMID- 10963616
TI  - Controversies in the medical management of persistent and recurrent acute otitis
      media. Recommendations of a clinical advisory committee.
AB  - Streptococcus pneumoniae is the predominant bacterial pathogen associated with
      acute otitis media (AOM), causing an estimated 7 million cases annually in the
      United States. Bacterial resistance should be considered when selecting an
      antimicrobial agent for otitis media. Significant increases in drug-resistant S
      pneumoniae are documented worldwide, and less than 50% of S pneumoniae strains
      are fully susceptible to penicillin in some regions of the United States.
      Although amoxicillin is recommended for uncomplicated AOM, treatment guidelines
      should be flexible and adaptable, taking into consideration local and regional
      susceptibility patterns, the age of the patient, the frequency of prior
      infections, and the response to prior therapy. Resistant organisms are more
      prevalent in children younger than 2 years of age and in those who have recurrent
      or persistent AOM. Overdiagnosing AOM, selecting inappropriate empiric therapy,
      or both, leads to overuse and misuse of antibiotics and causes increased drug
      resistance. This article reviews persistent and recurrent AOM and discusses the
      pitfalls of diagnosis and the practical limitations of current treatment
      recommendations.

PMID- 10963617
TI  - Estrogens as Endogenous Carcinogens in the Breast and Prostate. Conference
      proceedings. Chantilly, Virginia, USA. March 15-17, 1998.

PMID- 10963618
TI  - Developmental, cellular, and molecular basis of human breast cancer.
AB  - Breast cancer, which is the most common neoplastic disease in females and
      accounts for up to one third of all new cases of women's cancer in North America,
      continues to rise in incidence. In addition, the mortality caused by this disease
      has remained almost unchanged for the past 5 decades, becoming only second to
      lung cancer as a cause of cancer-related death. The failure in eradicating this
      disease is largely due to the lack of identification of a specific etiologic
      agent, the precise time of initiation, and the molecular mechanisms responsible
      for cancer initiation and progression. Despite the numerous uncertainties
      surrounding the origin of cancer, there is substantial evidence that breast
      cancer risk relates to endocrinologic and reproductive factors. The development
      of breast cancer strongly depends on the ovary and on endocrine conditions
      modulated by ovarian function, such as early menarche, late menopause, and
      parity. However, the specific hormone or hormone combinations responsible for
      cancer initiation have not been identified, and their role as protective or risk
      factors is still incompletely understood. A highly significant female hormone is
      estrogen, which is involved in the development of a variety of cancers, but it is
      still unclear whether estrogens are carcinogenic to the human breast. An
      understanding of whether estrogens cause mutations, and, if so, whether they act
      through hormonal effects activated by receptor binding, cytochrome P450-mediated
      metabolic activation, or compromise the DNA repair system, is essential for
      determining whether this steroid hormone is involved in the initiation or
      progression of breast cancer. This knowledge has to be based on a
      multidisciplinary approach encompassing studies of the development of the breast,
      influence of hormones on the differentiation of individual structures, and their
      interrelations in the pathogenesis of breast cancer. The analysis of the
      mechanisms involved would require confirmation in the adequate in vitro models
      and determination of the role played by genomic alterations in both cancer
      initiation and progression.

PMID- 10963619
TI  - The role of steroid hormones in prostate carcinogenesis.
AB  - Carcinoma of the prostate is the most frequently diagnosed malignancy and the
      second leading cause of death as a result of cancer in men in the United States
      and in many other Western countries. Notwithstanding the importance of this
      malignancy, little is understood about its causes. The epidemiology of prostate
      cancer strongly suggests that environmental factors, particularly diet and
      nutrition, are major determinants of risk for this disease, and evidence is
      mounting that there are important genetic risk factors for prostate cancer. Human
      prostate carcinomas are often androgen sensitive and react to hormonal therapy by
      temporary remission, followed by relapse to an androgen-insensitive state. These
      well-established features of prostate cancer strongly suggest that steroid
      hormones, particularly androgens, play a major role in human prostatic
      carcinogenesis, but the precise mechanisms by which androgens affect this process
      are unknown. In addition, the possible involvement of estrogenic hormones is not
      entirely clear. The purpose of this overview is to summarize the literature about
      steroid hormonal factors, androgens and estrogens, and prostate carcinogenesis.
      From these literature observations, a multifactorial general hypothesis of
      prostate carcinogenesis emerges with androgens as strong tumor promoters acting
      via androgen receptor-mediated mechanisms to enhance the carcinogenic activity of
      strong endogenous genotoxic carcinogens, such as reactive estrogen metabolites
      and estrogen- and prostatitis-generated reactive oxygen species and possible weak
      environmental carcinogens of unknown nature. In this hypothesis, all of these
      processes are modulated by a variety of environmental factors such as diet and by
      genetic determinants such as hereditary susceptibility and polymorphic genes that
      encode for steroid hormone receptors and enzymes involved in the metabolism and
      action of steroid hormones.

PMID- 10963620
TI  - Endogenous estrogens as carcinogens through metabolic activation.
AB  - A common thread linking the main risks for developing breast cancer in women is
      cumulative, excessive exposure to estrogen. The standard paradigm to account for
      this association focuses on increased cell proliferation caused by estrogen
      through estrogen receptor-mediated signal transduction accompanied by increased
      probability for mutation to occur during DNA synthesis. This chapter provides an
      overview of the mounting evidence, provided from cell culture and whole animal
      experimental studies, in support of a role for the oxidative metabolites of
      estrogen, in particular, the catechol estrogens, in the development of estrogen
      carcinogenesis. This provides a paradigm for how estrogens may contribute to the
      development of human breast cancer. The chapters that follow will fill in the
      details. Evidence shows that the catechols themselves are signaling molecules
      that work through the estrogen receptor. In addition, upon further oxidation, the
      catechols can give rise to reactive quinones capable of forming direct adducts
      with glutathione and purines in DNA and of redox cycling to generate reactive
      oxygen species that can cause oxidative damage. Estradiol and estrone, as well as
      their 4-hydroxy catechols, are carcinogenic in the Syrian golden hamster kidney,
      and ethinyl estradiol is a strong promoter of hepatocarcinogenesis in the rat.
      Increased oxidative DNA damage has been detected in target tissues after estrogen
      treatment in both animal model systems. Furthermore, several recent molecular
      epidemiologic studies have found that a polymorphism associated with a low
      activity form of catechol-O-methyltransferase, an enzyme involved in the
      inactivation of catechol estrogens, is associated with an increased risk for
      developing breast cancer. The increased risk is observed in certain women,
      although the studies are not consistent on which subgroup of women (e.g.,
      premenopausal or postmenopausal) is at increased risk, and one study detected no
      increased risk. Reasons for such discrepancies are discussed in light of factors,
      such as genetic polymorphisms and environmental/lifestyle susceptibility factors,
      which control the tissue-specific balance within cells among the estrogen
      metabolites. It is concluded that such factors will have to be identified through
      additional mechanistic studies and that, as they are identified, they can be
      incorporated into future molecular epidemiologic studies designed to determine
      their actual impact on cancer risk in human populations.

PMID- 10963621
TI  - Estrogens as endogenous genotoxic agents--DNA adducts and mutations.
AB  - Estrogens induce tumors in laboratory animals and have been associated with
      breast and uterine cancers in humans. In relation to the role of estrogens in the
      induction of cancer, we examine formation of DNA adducts by reactive
      electrophilic estrogen metabolites, formation of reactive oxygen species by
      estrogens and the resulting indirect DNA damage by these oxidants, and, finally,
      genomic and gene mutations induced by estrogens. Quinone intermediates derived by
      oxidation of the catechol estrogens 4-hydroxyestradiol or 4-hydroxyestrone may
      react with purine bases of DNA to form depurinating adducts that generate highly
      mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated estrogens
      produce less harmful, stable DNA adducts. The catechol estrogen metabolites may
      also generate potentially mutagenic oxygen radicals by metabolic redox cycling or
      other mechanisms. Several types of indirect DNA damage are caused by estrogen
      induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct
      formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and
      the synthetic estrogen diethylstilbestrol also induce numerical and structural
      chromosomal aberrations and several types of gene mutations in cells in culture
      and in vivo. In conclusion, estrogens, including the natural hormones estradiol
      and estrone, must be considered genotoxic carcinogens on the basis of the
      evidence outlined in this chapter.

PMID- 10963622
TI  - Tissue-specific synthesis and oxidative metabolism of estrogens.
AB  - Estrogen exposure represents the major known risk factor for development of
      breast cancer in women and is implicated in the development of prostate cancer in
      men. Human breast tissue has been shown to be a site of oxidative metabolism of
      estrogen due to the presence of specific cytochrome P450 enzymes. The oxidative
      metabolism of 17beta-estradiol (E2) to E2-3,4-quinone metabolites by an E2-4
      hydroxylase in breast tissue provides a rational hypothesis to explain the
      mammary carcinogenic effects of estrogen in women because this metabolite is
      directly genotoxic and can undergo redox cycling to form genotoxic reactive
      oxygen species. In this chapter, evidence in support of this hypothesis and of
      the role of P4501B1 as the 4-hydroxylase expressed in human breast tissue is
      reviewed. However, the plausibility of this hypothesis has been questioned on the
      grounds that insufficient E2 is present in breast tissue to be converted to
      biologically significant amounts of metabolite. This critique is based on the
      assumption that plasma and tissue E2 levels are concordant. However, breast
      cancer tissue E2 levels are 10-fold to 50-fold higher in postmenopausal women
      than predicted from plasma levels. Consequently, factors must be present to alter
      breast tissue E2 levels independently of plasma concentrations. One such factor
      may be the local production of E2 in breast tissue through the enzyme aromatase,
      and the evidence supporting the expression of aromatase in breast tissue is also
      reviewed in this chapter. If correct, mutations or environmental factors
      enhancing aromatase activity might result in high tissue concentrations of E2
      that would likely be sufficient to serve as substrates for CYP1B1, given its high
      affinity for E2. This concept, if verified experimentally, would provide
      plausibility to the hypothesis that sufficient E2 may be present in tissue for
      formation of catechol metabolites that are estrogenic and which, upon further
      oxidative metabolism, form genotoxic species at levels that may contribute to
      estrogen carcinogenesis.

PMID- 10963623
TI  - Estrogen metabolism by conjugation.
AB  - The involvement of estrogens in carcinogenic processes within estrogen-responsive
      tissues has been recognized for a number of years. Classically, mitogenicity
      associated with estrogen receptor-mediated cellular events was believed to be the
      mechanism by which estrogens contributed to carcinogenesis. Recently, the
      possibility that estrogens might contribute directly to mutagenesis resulting
      from DNA damage has been investigated. That damage is apparently a result of the
      formation of catechol estrogens that can be further oxidized to semiquinones and
      quinones. Those molecules represent reactive oxygen species and electrophilic
      molecules that can form depurinating DNA adducts, thus having the potential to
      result in permanent nucleotide mutation. Conjugation of parent estrogens to
      sulfate and glucuronide moieties; of catechol estrogens to methyl, sulfate, and
      glucuronide conjugates; and of catechol estrogen quinones to glutathione
      conjugates all represent potential "detoxification" reactions that may protect
      the cell from estrogen-mediated mitogenicity and mutagenesis. In this chapter,
      the biochemistry and molecular genetics of those conjugative reaction pathways
      are discussed. When applicable, the involvement of specific enzymatic isoforms is
      presented. Finally, the activity of many of these conjugative biotransformation
      reactions is subject to large interindividual variation--often due to the
      presence of common nucleotide polymorphisms within the genes encoding those
      enzymes. Functionally significant genetic polymorphisms that might contribute to
      variable conjugation of estrogens and catechol estrogens are also discussed.

PMID- 10963624
TI  - Molecular epidemiology of genetic polymorphisms in estrogen metabolizing enzymes
      in human breast cancer.
AB  - Epidemiologic studies indicate that most risk factors for breast cancer are
      related to reproductive and hormonal factors. For a number of years, the
      mechanism for estrogens in carcinogenesis was thought to be that of mitotic
      stimulation, with the growth promotion of ductal epithelial cells harboring
      precursor mutations in the breast. However, evidence is now available that
      estrogens may act as initiators of cellular alterations and tumorigenesis.
      Investigation and measurement of serum levels of estrogens in epidemiologic
      studies may, therefore, be misleading, because they may reflect levels quite
      different from those of hormone metabolites to which the target tissue is
      exposed. Proportions of hormone metabolites may be estimated by evaluation of
      associations between breast cancer risk and genetic polymorphisms in enzymes
      involved in hormone metabolism. A number of molecular epidemiologic studies have
      been conducted to evaluate associations between polymorphic genes involved in
      steroid hormone metabolism (i.e., CYP17, COMT, CYP1A1, CYP19, GST, and MnSOD)
      that may account for a proportion of enzymatic variability, and results are
      discussed in this review. There are strengths and limitations to such an
      approach, foremost of which may be the lack of insight into the extent to which
      individual variability in estrogen exposure may be explained by allelic
      variation. Variability in other endogenous and exogenous factors that impact
      parent hormones and their metabolites along activation and conjugation pathways
      may also affect associations in case-control comparisons. This and other possible
      reasons for inconsistencies in results of molecular epidemiologic studies are
      discussed. Contributions from population-based studies and those from the
      laboratory may together move this field ahead and more clearly elucidate the
      basis of hormonally related cancers, identifying etiologic factors and
      susceptible populations for preventive strategies.

PMID- 10963625
TI  - Estrogen receptor-mediated processes in normal and cancer cells.
AB  - The role of estrogens in breast and other cancers has been extensively
      investigated for many years, and historically most of these studies have focused
      on the hormonal regulation of cell proliferation. The most recent work in this
      area has focused on the expression of genes likely to mediate proliferation
      (e.g., growth factors, proto-oncogenes, etc.) and their regulation by the classic
      nuclear estrogen receptor, ER-alpha. In this chapter, we present a synopsis of
      several new developments in this area of ER-regulated gene expression. These
      developments include the following: 1) the selective activation of ER domains by
      partial estrogen antagonists, such as tamoxifen and other ligands; 2) the effects
      of ER-alpha overexpression and gene knockout on the development of breast and
      uterine cancers in experimental animal models; 3) mechanisms by which steroid
      hormones regulate programmed cell death, cell cycle progression, cell-substratum
      interactions, and genomic instability in cancer cells; 4) identification of
      nuclear proteins that interact with the ER in the presence of agonists and
      antagonists, the effect of ligand binding on the receptor structure, and the
      interactions of liganded and nonliganded receptors with coactivators,
      corepressors, and other regulatory proteins; and 5) the biochemical properties,
      cellular distribution, and potential biologic roles for the newly discovered ER
      beta. Although there is an increasing interest in understanding the role of
      estrogens as endogenous carcinogens, it remains clear that ER-mediated regulation
      of gene expression plays many significant roles in normal and cancer cells, and
      increased knowledge of the mechanisms involved will improve our overall
      understanding of hormonal carcinogenesis.

PMID- 10963626
TI  - Factors critical to the design and execution of epidemiologic studies and
      description of an innovative technology to follow the progression from normal to
      cancer tissue.
AB  - The results obtained from experimental studies of estrogen carcinogenesis need
      validation in epidemiologic studies. Such studies present additional challenges,
      however, because variations in human populations are much greater than those in
      experimental systems and in animal models. Because epidemiologic studies are
      often used to evaluate modest differences in risk factors, it is essential to
      minimize sources of errors and to maximize sensitivity, reproducibility, and
      specificity. In the first part of this chapter, critical factors in designing and
      executing epidemiologic studies, as well as the influence of sample collection,
      processing, and storage on data reliability, are discussed. One of the most
      important requirements is attaining sufficient statistical power to assess small
      genetic effects and to evaluate interactions between genetic and environmental
      factors. The second part of this chapter describes innovative technology, namely,
      Fourier transform-infrared (FT-IR) spectra of DNA that reveal major structural
      differences at various stages of the progression from normal to cancer tissue.
      The structural differences become evident from wavenumber-by-wavenumber
      statistical comparisons of the mean FT-IR spectra of DNA from normal to cancer
      tissues. This analysis has allowed distinguishing benign tissues from cancer and
      metastatic tissues in human breast, prostate, and ovarian cancers. This analysis,
      which requires less than 1 microg of DNA, is predicted to be used for detecting
      early cancer-related changes at the level of DNA, rather than at the cellular
      level.

PMID- 10963627
TI  - Hope for prevention--perspective of the cancer advocate.
AB  - Breast and prostate cancer survivors and advocates participated as panelists with
      scientists in an interactive panel discussion following 2 days of scientific
      presentations on "Estrogens as Endogenous Carcinogens in the Breast and
      Prostate." Advocates raised several issues of concern and questions related to
      the research presented. Concerns included the following: 1) a global fear of
      developing either breast or prostate cancer and recurrence from these tumors, 2)
      a specific fear that estrogen replacement therapy could enhance the development
      of new breast cancers and stimulate recurrence in breast cancer survivors, and 3)
      a concern that researchers examining minority communities should have sensitivity
      to the specific culture under study and an understanding of specific research
      issues that are relevant in those communities. The questions raised included the
      following: 1) What are the implications of resistance to antiestrogen therapies
      and what is the appropriate sequencing of hormone therapy for longer-term
      benefit? 2) Can one identify women and men at risk for cancer who do not have the
      usual risk factors? 3) Where does the development of blood or urine tests to
      screen for cancer currently stand? 4) Can research findings be translated into
      effective therapies more rapidly? 5) Can the status of this translational process
      be communicated to the public in a meaningful way by breaking down language
      barriers? 6) What means are available to develop more creative ways to fund pilot
      studies that do not require preliminary data and to create new funding mechanisms
      to respond to the needs of scientists, particularly those that work
      collaboratively from multiple institutions and multidisciplines? 7) How can the
      need for increased emphasis on and visibility for prostate cancer be
      communicated? Following the interactive dialogue, scientists and advocates
      suggested more collaborative research with sustained funding avenues, continued
      dialogue and collaboration between scientists and advocates, and more
      collaborative research groups like the Cancer Cube.

PMID- 10963628
TI  - Age-dependent cerebral hemodynamic effects of traumatic brain injury in newborn
      and juvenile pigs.
AB  - Traumatic brain injury is one of the major causes of morbidity, mortality, and
      pediatric intensive care unit admissions of children. Although the effects of
      traumatic brain injury have been well described for adult animal models, few have
      investigated these effects in the newborn or have characterized such effects as a
      function of age using a single model of injury. Using a piglet model of brain
      injury, recent studies have shown that the cerebral hemodynamic effects and the
      corresponding mechanisms for such effects of injury vary as a functional of age.
      This review discusses the types of traumatic brain injury, their models, and the
      role of species in such model choice. This review also describes the effects of
      brain injury on cerebral blood flow, metabolism, and cerebrovascular regulation
      as a function of age. Finally, this review presents evidence for potential
      mechanisms that may contribute to age-dependent impaired cerebral hemodynamics
      following brain injury.

PMID- 10963629
TI  - Theoretical simulation of oxygen transport to brain by networks of microvessels:
      effects of oxygen supply and demand on tissue hypoxia.
AB  - OBJECTIVE: Simulations of oxygen delivery by a three-dimensional network of
      microvessels in rat cerebral cortex were used to examine how the distribution of
      partial pressure of oxygen (PO2) in tissue depends on blood flow and oxygen
      consumption rates. METHODS: Network geometry was deduced from previously
      published scanning electron micrographs of corrosion casts. A nonlinear least
      squares method, using images obtained at three different angles, was used to
      estimate vessel locations. The network consisted of 50 segments in a region 140
      microm x 150 microm x 160 microm. A Green's function method was used to predict
      the PO2 distribution. Effects of varying perfusion and consumption were examined,
      relative to a control state with consumption 10 cm3O2/100 g per min and perfusion
      160 cm3/100 g per min. RESULTS: In the control state, minimum tissue PO2, was 7
      mm Hg. A Krogh-type model with the same density of vessels, but with uniform
      spacing, predicted a minimum tissue PO2 of 23 mm Hg. For perfusion below 60% of
      control, tissue hypoxia (PO2 <1 mm Hg) was predicted. When perfusion was reduced
      by 75%, the resulting hypoxia could be eliminated by a 31% reduction in oxygen
      consumption rate. CONCLUSIONS: The simulations suggest that tissue hypoxia
      resulting from a severe decrease in brain perfusion, as can occur in stroke, may
      be avoided by a moderate decrease in oxygen consumption rate.

PMID- 10963630
TI  - Expression of endothelial cell adhesion molecules in neovascularized tissue.
AB  - OBJECTIVE: Recent studies indicate that endothelial cells of newly formed blood
      vessels are activated and exhibit a distinct phenotype that may influence the
      responses of these microvessels to an inflammatory stimulus. The objective of
      this study was to compare the basal and cytokine-stimulated expression of
      endothelial cell adhesion molecules in neovascularized tissue to normal
      (nonproliferating) vascular beds. METHODS: The expression of P- and E-selectin.
      VCAM-1, ICAM-1, ICAM-2, and PECAM-1 was measured, using the dual radiolabeled mAb
      technique, in subcutaneously implanted (for 10-15 days) polyurethane sponges,
      skin, heart, lung, and intestine of male C57BL/6 mlice (background). RESULTS:
      Basal values of PECAM-1 and ICAM-2 revealed a low vascular density in the
      implanted sponge matrices that is comparable to skin. When normalized for
      vascular surface area (PECAM-1 or ICAM-1 expression), the basal level of E- and P
      selectin expression was highest in neovascularized sponge and skin. TNF-alpha
      elicited an increased expression of all endothelial CAMs, except PECAM-1 and ICAM
      2, but the responses were blunted in sponge and skin, relative to other vascular
      beds. CONCLUSIONS: These findings indicate that endothelial cells in newly formed
      blood vessels exhibit a pattern of basal and cytokine-induced expression of
      certain adhesion glycoproteins that is similar to nonproliferating cutaneous
      vessels.

PMID- 10963632
TI  - Effects of myocardial edema on the development of myocardial interstitial
      fibrosis.
AB  - OBJECTIVE: The mechanism by which chronic myocardial edema causes cardiac
      dysfunction is poorly understood. We hypothesized that myocardial edema triggers
      cardiac fibrosis development resulting in cardiac dysfunction. Since collagen is
      the most abundant constituent of the interstitial matrix, we examined the effects
      of edema development on cardiac collagen metabolism. METHODS: We utilized a
      chronic pulmonary artery banded rat model that produces right ventricular
      hypertrophy with myocardial edema and left ventricular edema without hypertrophy
      or hyperplasia. Wet to dry ratios (index of edema), collagen type I and III
      concentrations, prolyl 4-hydroxylase (P4-H) and collagen type I and III mRNA
      levels, collagenase activity and transforming growth factor-beta were measured in
      both ventricles. RESULTS: Right and left ventricular wet to dry ratios were
      significantly elevated from 1 to 28 days after pulmonary artery banding compared
      to sham rats. Right and left ventricular collagen types I and III and P4-H mRNA
      levels increased significantly at 3 days followed by significant increases in
      right and left ventricular collagen concentration 7 days after pulmonary artery
      banding. Right ventricular collagenase activity increased at 3 days while left
      ventricular collagenase activity decreased 7 days after PA banding. CONCLUSIONS:
      We conclude that myocardial edema preceded the observed increase in collagen
      deposition and that edema may have triggered increased collagen synthesis by
      fibroblasts. leading to fibrosis development.

PMID- 10963631
TI  - Requirement of arteriovenular pairing for increased capillary filtration during
      acute inflammation.
AB  - OBJECTIVE: The purpose of this study was to determine whether the leukocyte
      chemoattractant N-formyl methionyl-leucyl-phenylalanine (FMLP) increases
      capillary fluid filtration rate (Jv/S), and if so, to determine whether the
      mechanism involves arteriovenular communication. METHODS: Intravital microscopy
      was used in the rat mesentery to measure capillary Jv/S by a micro-occlusion
      technique. FMLP was locally superfused through a micropipette near vessels in
      three different arrangements: 1) near a venule in close pairing with the
      arteriole feeding the monitored capillary, 2) near an unpaired arteriole feeding
      the capillary, or 3) near an unpaired venule draining the capillary. In separate
      experiments, arteriolar hydrostatic pressure (downstream of arteriovenular
      pairing sites exposed to FMLP) was measured with a micropressure system. RESULTS:
      FMLP increased capillary Jv/S when applied to arteriovenular pairing sites, but
      not when applied to unpaired arterioles or venules. Micropressure measurements in
      paired arterioles remained essentially constant during FMLP exposure, suggesting
      that the increase in Jv/S is primarily due to increased capillary permeability.
      CONCLUSIONS: With FMLP applied locally to stimulate leukocytes, arteriovenular
      pairing is required to observe an increase in capillary filtration rate.

PMID- 10963633
TI  - Contribution of extrinsic factors and intrinsic vascular alterations to reduced
      arteriolar reactivity with high-salt diet and hypertension.
AB  - OBJECTIVE: To determine whether the impaired relaxation of skeletal muscle
      arterioles of rats on high-salt diet or with reduced renal mass hypertension (RRM
      HT) represents intrinsic alterations to microvessels alone, or whether
      extravascular influences also contribute to reduced dilator responses. METHODS:
      Normotensive (NT) Sprague-Dawley rats were fed low-salt (LS) or high-salt (HS)
      diets, and RRM-HT rats were fed HS diet for 4-6 weeks. In situ and isolated
      cremaster muscle first-order arterioles (1A) were examined using television
      microscopy, and a video micrometer was used to measure diameter changes in
      response to acetylcholine (ACH), cholera toxin (CT), and sodium nitroprusside
      (SNP). RESULTS: Compared to normotensive low-salt (NT-LS) rats, responses of 1A
      to the agonists were reduced in normotensive high-salt (NT-HS) and RRM-HT rats.
      Arteriolar reactivity to the agonists in NT-LS rats aid in NT-HS rats was not
      different between in situ and in vitro environments. However, in RRM-HT rats, the
      reactivity of 1A to each agonist was greater in isolated arterioles than in in
      situ arterioles. CONCLUSIONS: These results suggest that the impaired response of
      skeletal muscle arterioles to vasodilator stimuli in normotensive rats on high
      salt diet primarily reflects alterations to microvessels alone, while reduced
      dilator responses in RRM-HT rats represent a combination of extravascular
      influences and intrinsic alterations to arterioles themselves.

PMID- 10963634
TI  - Venous thromboembolism in malignancy.

PMID- 10963635
TI  - Incidence of recurrent thromboembolic and bleeding complications among patients
      with venous thromboembolism in relation to both malignancy and achieved
      international normalized ratio: a retrospective analysis.
AB  - PURPOSE: Initial heparinization followed by vitamin K antagonists is the
      treatment of choice for patients with venous thromboembolism. There is
      controversy whether known malignancy is a risk factor for recurrences and
      bleeding complications during this treatment. Furthermore, the incidence of such
      events in these patients is dependent on the achieved International Normalized
      Ratio (INR). The aim of this study was to assess the incidence of venous
      thromboembolic recurrence and major bleeding among patients with venous
      thromboembolism in relation to both malignancy and the achieved INR. PATIENTS AND
      METHODS: In a retrospective analysis, the INR-specific incidence of venous
      thromboembolic and major bleeding events during oral anticoagulant therapy was
      calculated separately for patients with and without malignancy. Eligible patients
      participated in two multicenter, randomized clinical trials on the initial
      treatment of venous thromboembolism. Patients were initially treated with heparin
      (standard or low-molecular weight). Treatment with vitamin K antagonists was
      started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.
      RESULTS: In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12
      bleeds occurred. Patients with malignancy, compared with nonmalignant patients,
      had a clinically and statistically significantly increased overall incidence of
      recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding
      (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients,
      the incidence of recurrence was lower when the INR was above 2.0 compared with
      below 2.0. CONCLUSION: Although adequately dosed vitamin K antagonists are
      effective in patients with malignant disease, the incidence of thrombotic and
      bleeding complications remains higher than in patients without malignancy.

PMID- 10963636
TI  - Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and
      carboplatin in advanced ovarian cancer.
AB  - PURPOSE: To determine the side effects and feasibility of cisplatin and
      carboplatin each in combination with paclitaxel as front-line therapy in advanced
      epithelial ovarian cancer. PATIENTS AND METHODS: Patients were randomly allocated
      to receive paclitaxel 175 mg/m(2) intravenously as a 3-hour infusion followed by
      either cisplatin 75 mg/m(2) or carboplatin (area under the plasma concentration
      time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at
      least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the
      hospital, whereas the carboplatin regimen was administered to outpatients.
      RESULTS: A total of 208 eligible patients were randomized. Both regimens could be
      delivered in an optimal dose and without significant delay. Paclitaxel
      carboplatin produced significantly less nausea and vomiting (P: <.01) and less
      peripheral neurotoxicity (P: =.04) but more granulocytopenia and thrombocytopenia
      (P: <.01). The overall response rate in 132 patients with measurable disease was
      64% (84 of 132 patients), and in patients with elevated CA 125 levels at start,
      it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the
      median progression-free survival time of all patients was 16 months and the
      median overall survival time was 31 months. The small number of patients entered
      onto the study caused wide confidence intervals (CIs) around the hazards ratio
      for progression-free survival of paclitaxel-carboplatin compared with paclitaxel
      cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow
      conclusions about efficacy. CONCLUSION: Paclitaxel-carboplatin is a feasible
      regimen for outpatients with ovarian cancer and has a better toxicity profile
      than paclitaxel-cisplatin.

PMID- 10963637
TI  - Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory
      epithelial ovarian cancer.
AB  - PURPOSE: Stealth liposomal doxorubicin (Alzal Corp, Palo Alto, CA) has a slower
      clearance rate than free doxorubicin, resulting in sustained serum levels.
      Liposomal encapsulation also leads to increased concentration of drug in tumor
      tissue. Meta-analysis of previous studies has shown that doxorubicin has activity
      in epithelial ovarian cancer. The current study was developed to examine the
      activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory
      ovarian cancer. PATIENTS AND METHODS: Patients had epithelial ovarian cancer that
      either progressed on or recurred within 6 months of completion of platinum and
      paclitaxel chemotherapy. All patients had measurable disease. Stealth liposomal
      doxorubicin was administered at 50 mg/m(2) every 4 weeks as a 1-hour infusion.
      RESULTS: Eighty-nine patients were treated and included in an intent-to-treat
      analysis. There were 82 patients who were platinum and paclitaxel refractory and
      met all study criteria. There was one complete response and 14 partial responses,
      for a total response rate of 16.9% (95% confidence interval [CI], 9.1% to 24.6%).
      For platinum- and paclitaxel-refractory patients, the response rate was 18.3%
      (95% CI, 9.9% to 26.7%). Median time to progression was 19. 3 weeks for the
      entire population. Ten patients (11.2%) withdrew because of adverse events
      related to the drug (palmar-plantar erythrodysesthesia [PPE], n = 3; asthenia, n
      = 2; cardiac, n = 2; neutropenia, n = 1; stomatitis, n = 1; and edema, n = 1).
      There were no drug-related fatal events. There were only eight grade 4 adverse
      events attributable to the drug. Stomatitis, PPE, and skin lesions were managed
      with dose reductions and delays in most cases. CONCLUSION: Stealth liposomal
      doxorubicin has activity in refractory epithelial ovarian cancer. PPE and
      stomatitis can usually be managed by dose adjustment. The ease of administration
      makes this an attractive agent.

PMID- 10963639
TI  - Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the
      European Intergroup Cooperative Ewing's Sarcoma Study Group.
AB  - PURPOSE: To further elaborate on prognostic factors for Ewing's sarcoma of bone
      and to document improvements in relapse-free survival (RFS) and trends in local
      therapy over the study period (1977 to 1993). PATIENTS AND METHODS: A
      retrospective analysis was performed on a combined Gesellschaft Fur Padiatrische
      Onkologie und Hamatologie/Cooperative Ewing Sarcoma Study and United Kingdom
      Children's Cancer Study Group/Medical Research Council data set of 975 patients
      registered with the respective trial offices before the current collaborative
      European Intergroup Cooperative Ewing's Sarcoma Study trial. Both groups
      independently undertook studies with similar chemotherapy during the period.
      RESULTS: The key adverse prognostic factor is metastases at diagnosis (5-year
      RFS, 22% of patients with metastases at diagnosis v 55% of patients without
      metastases at diagnosis; P: <.0001). For the group with metastases, there was a
      trend for better survival for those with lung involvement compared with those
      with bone metastases or a combination of lung and bone metastases (P: <.0001). In
      the group of patients with no metastases at diagnosis, multivariate analysis
      demonstrated that site (axial v other), age-group (< 15 v > or = 15 years), and
      period of diagnosis had significant influence on RFS (all P: <.005). RFS was
      superior in the period after 1985 compared with the period before 1985 for
      nonmetastatic patients (45% v 60%, respectively; P: <.0001) and for metastatic
      patients (16% v 30%, respectively; P: =.016). Patients who relapsed within 2
      years of diagnosis had a less favorable prognosis than patients who relapsed
      later (5-year survival after relapse, 4% v 23%, respectively; P: <. 0001). There
      were other changes over the period; in particular, radiotherapy or amputation
      were more common in the period before 1986, whereas endoprosthetic surgery was
      widely used in the later period. CONCLUSION: Survival and RFS improved over the
      period. Prognostic factors are metastases at diagnosis, primary site, and age.

PMID- 10963638
TI  - Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic
      Cooperative Oncology Group Study.
AB  - PURPOSE: To evaluate the efficacy of the carboplatin/paclitaxel combination in
      patients with carcinoma of unknown primary site (CUP). PATIENTS AND METHODS:
      Seventy-seven consecutive CUP patients (45 women and 32 men; median age, 60
      years) were treated with carboplatin at target area under the curve 6 mg/mL/min
      followed by paclitaxel 200 mg/m(2) as a 3-hour infusion and granulocyte colony
      stimulating factor from days 5 to 12. Treatment courses were repeated every 3
      weeks to a maximum of eight cycles. Forty-seven patients had adenocarcinomas, 27
      had undifferentiated carcinomas, and three had squamous cell carcinomas. Thirty
      three patients presented with liver, bone, or multiple organ metastases, 23 with
      predominantly nodal/pleural disease, and 19 (16 women) with peritoneal
      carcinomatosis. RESULTS: The overall response rate by intent-to-treat analysis
      was 38.7% (95% confidence interval, 27.5% to 49.9%). There were no differences in
      response between adenocarcinomas and undifferentiated carcinomas, but efficacy
      varied among clinical subsets. The response rates and median survival times in
      the three clinically defined subsets were 47.8% and 13 months, respectively, for
      patients with predominantly nodal/pleural disease, 68.4% and 15 months,
      respectively, in women with peritoneal carcinomatosis, and 15.1% and 10 months,
      respectively, in patients with visceral or disseminated metastases. Chemotherapy
      was well-tolerated. CONCLUSION: Carboplatin plus paclitaxel combination
      chemotherapy is effective in patients with predominantly nodal/pleural metastases
      of unknown primary carcinoma and in women with peritoneal carcinomatosis.
      However, in patients with liver, bone, or multiple organ involvement, the
      combination offers limited benefit. The investigation of novel treatment
      approaches is highly warranted for this group of patients.

PMID- 10963640
TI  - Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose
      intensity and duration of treatment.
AB  - PURPOSE: To determine whether the duration and the dose of epirubicin modify the
      long-term outcome of patients with metastatic breast cancer (MBC). PATIENTS AND
      METHODS: Four hundred seventeen anthracycline-naive MBC patients were randomized
      to receive one of the following regimens: arm A: 11 cycles of fluorouracil 500
      mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every
      21 days; arm B: four cycles of FEC 100 (same regimen but with epirubicin 100
      mg/m(2)) then eight cycles of FEC 50 (epirubicin 50 mg/m(2)); and arm C: four
      cycles of FEC 100 then restart the same regimen at disease progression in case of
      prior response or stabilization. RESULTS: Hematologic toxicity was similar.
      Nausea/vomiting and stomatitis were significantly less frequent in arm A as was
      left ventricular ejection fraction decrease in arm C (A = six patients, B = five
      patients, and C = one patient). Six patients died of infections (A = four
      patients and C = two patients). After four cycles, the objective response rate
      (ORR) was better with FEC 100 than with FEC 75 (49.2% v 40%, respectively; P:
      =.07). The ORR was better with the longer regimens (arm A, 56.9%; B, 64%; and C,
      47.6%; P: =.06) and was 41% after second-line FEC 100. After a median follow-up
      of 41 months, the response duration and time to progression (TTP) were
      significantly better with arm B, the longer regimen (P: =.012 and P: < 10(-3),
      respectively). The median survival times for arms A, B, and C were similar (17.9,
      18.9, and 16. 3 months, respectively; P: =.49). CONCLUSION: In MBC, longer
      epirubicin-based regimens are better in terms of response duration and TTP. FEC
      100 regimens improve the ORR. However, four initial cycles of FEC 100 and
      identical retreatment at disease progression yielded equivalent overall survival
      to longer regimens.

PMID- 10963641
TI  - Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and
      fluorouracil in patients with node-negative, rapidly proliferating breast cancer:
      a randomized multicenter study.
AB  - PURPOSE: According to one of the most recent key scientific questions concerning
      the use of biomarkers in clinical trials, we investigated whether node-negative
      breast cancer patients, defined as high-risk cases on the basis of tumor cell
      proliferation, could benefit from cyclophosphamide, methotrexate, and
      fluorouracil (CMF) adjuvant therapy. PATIENTS AND METHODS: Two hundred eighty-one
      patients with negative nodes and rapidly proliferating tumors, defined according
      to thymidine labeling index (TLI), were randomized to receive six cycles of CMF
      or no further treatment after surgery +/- radiotherapy. RESULTS: The 5-year
      disease-free survival (DFS) was 83% for patients treated with CMF compared with
      72% in the control group (P: =.028). Adjuvant treatment reduced both locoregional
      and distant metastases. When clinical outcome was analyzed in cell kinetic
      subgroups characterized according to tertile criteria, compared with patients in
      the control arm, 5-year DFS was significantly higher after adjuvant CMF in
      patients with TLI values in the second (78% v 88%, respectively; P: =.037) and
      third tertiles (58% v 78%, respectively; P: =.024). CONCLUSION: The results from
      this randomized clinical study indicate that patients with node-negative, rapidly
      proliferating tumors significantly benefit from adjuvant CMF.

PMID- 10963642
TI  - Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety
      and efficacy of re-treatment.
AB  - PURPOSE: This phase II trial investigated the safety and efficacy of re-treatment
      with rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with low
      grade or follicular non-Hodgkin's lymphoma who relapsed after a response to
      rituximab therapy. PATIENTS AND METHODS: Fifty-eight patients were enrolled onto
      this study, and two were re-treated within the study. Patients received an
      intravenous infusion of 375 mg/m(2) of rituximab weekly for 4 weeks. All patients
      had at least two prior therapies and had received at least one prior course of
      rituximab, with a median interval of 14.5 months between rituximab courses.
      RESULTS: Most adverse experiences (AEs) were transient grade 1 or 2 events
      occurring during the treatment period. Clinically significant myelosuppression
      was not observed; hematologic toxicity was generally mild and reversible. No
      patient developed human antichimeric antibodies after treatment. The type,
      frequency, and severity of AEs in this study were not apparently different from
      those reported in the phase III trial of rituximab. The overall response rate in
      57 assessable patients was 40% (11% complete response and 30% partial responses).
      Median time to progression (TTP) in responders and median duration of response
      (DR) have not been reached, but Kaplan-Meier estimated medians are 17.8 months
      (range, 5.4+ to 26.6 months) and 16.3 months (range, 3.7+ to 25.1 months),
      respectively. These estimated medians are longer than the medians achieved in the
      patients' prior course of rituximab (TTP and DR of 12.4 and 9.8 months,
      respectively, P: >.1) and in a previously reported phase III trial (TTP in
      responders and DR of 13.2 and 11.6 months, respectively). Responses are ongoing
      in seven of 23 responders. CONCLUSION: In this re-treatment population, safety
      and efficacy were not apparently different from those after initial rituximab
      exposure.

PMID- 10963643
TI  - Treatment for primary CNS lymphoma: the next step.
AB  - PURPOSE: The use of preradiotherapy (RT) methotrexate (MTX) has improved disease
      control and survival in patients with primary CNS lymphoma (PCNSL). The reported
      protocol was designed to optimize and enhance the chemotherapeutic component of
      treatment. PATIENTS AND METHODS: Fifty-two patients were treated with five cycles
      of high-dose MTX 3.5 g/m(2), procarbazine 100 mg/m(2)/d, and vincristine 1.4
      mg/m(2). Thirty patients received whole-brain RT (45 Gy). Twenty-two older
      patients deferred RT to diminish the risk of delayed neurotoxicity; these
      patients are compared with 12 older patients who completed the entire treatment
      regimen. Most patients (n = 35) received high-dose cytarabine after RT. RESULTS:
      Objective response rate to the induction chemotherapy regimen was 90%; overall
      median survival is 60 months. Grade 3 or 4 myelosuppression was seen in 30
      patients, primarily in association with cytarabine; grade 3 nephrotoxicity due to
      MTX was seen in two patients. Older patients had similar median survival with or
      without the addition of RT: 32 versus 33 months, respectively. However, late
      neurotoxicity was significantly more common in those older patients who received
      RT (P: =.00004). Patients younger than 60 years who received the complete
      treatment regimen have not reached median disease-free or overall survival.
      CONCLUSION: Increasing the dose of MTX and adding procarbazine and vincristine
      improved disease control and overall survival in patients with newly diagnosed
      PCNSL. Younger patients in particular fared extremely well with this treatment
      regimen. In older patients, deferring whole-brain RT did not compromise overall
      survival but did reduce treatment-related toxicity.

PMID- 10963644
TI  - DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a
      phase I and pharmacokinetic study in patients with advanced solid malignancies.
AB  - PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate),
      a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily
      for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and
      pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of
      anticancer activity. PATIENTS AND METHODS: Patients with advanced solid
      malignancies were treated with escalating doses of DX-8951f. After three patients
      were treated at the first dose level, doses were to be escalated in increments of
      100%, using a single patient at each dose level unless moderate toxicity was
      observed. The MTD, defined as the highest dose level at which the incidence of
      dose-limiting toxicity did not exceed 20%, was calculated separately for
      minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and
      excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also
      characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX
      8951f at six dose levels ranging from 0.1 to 0.6 mg/m(2)/d. Brief, noncumulative
      neutropenia was the most common toxicity observed. Severe myelosuppression
      (neutropenia that was protracted and/or associated with fever and/or severe
      thrombocytopenia) was consistently experienced by HP and MP patients at doses
      exceeding 0.3 and 0.5 mg/m(2)/d, respectively. Nonhematologic toxicities (nausea,
      vomiting, and diarrhea) were also observed, but these effects were rarely severe.
      Objective antitumor activity included partial responses in one patient each with
      platinum-resistant extrapulmonary small-cell and fluoropyrimidine- and irinotecan
      resistant colorectal carcinoma, and minor responses in patients with prostate,
      hepatocellular, thymic, primary peritoneal, and irinotecan-resistant colorectal
      carcinomas. The PKs of total DX-8951 were linear and well fit by a three
      compartment model. CONCLUSION: The recommended doses for phase II studies of DX
      8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3
      mg/m(2)/d for MP and HP patients, respectively. The characteristics of the
      myelosuppressive effects of DX-8951f, paucity of severe nonhematologic
      toxicities, and antitumor activity against a wide range of malignancies warrant
      broad disease-directed evaluations of DX-8951f on this schedule.

PMID- 10963645
TI  - Phase I and pharmacokinetic study of a new taxoid, RPR 109881A, given as a 1-hour
      intravenous infusion in patients with advanced solid tumors.
AB  - PURPOSE: RPR 109881A is a new semisynthetic taxoid compound that has a similar
      mechanism of action to docetaxel. The purpose of this phase I study was to
      characterize the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetic
      profile, and antitumor effects of this agent. PATIENTS AND METHODS: Nineteen
      eligible patients with advanced solid tumors were enrolled. RPR 109881A was
      administered as a 1-hour intravenous infusion every 3 weeks at doses ranging from
      15 to 75 mg/m(2). Pharmacokinetic evaluation was performed at the first cycle.
      RESULTS: Neutropenia (febrile neutropenia) and fatigue were dose-limiting
      toxicities at doses of 60 and 75 mg/m(2) and seemed to be dose-related. Both
      thrombocytopenia and anemia were infrequent. Nonhematologic toxicities were
      generally mild. Pharmacokinetic studies indicated that RPR 109881A plasma
      disposition was bi- or triphasic, with a high total plasma clearance, a large
      volume of distribution, and a long terminal half-life. The area under the
      concentration-time curve (AUC) and the peak concentration of RPR 109881A seemed
      to increase with increasing dose proportionally, suggesting linear
      pharmacokinetics. Urinary excretion over 48 hours was low, with a mean of 0.8 +/-
      0.36% of the administered dose. A significant relationship existed between the
      percentage decrease of neutrophil counts and the AUC of RPR 109881A. Among 18
      assessable patients, two partial and two minor responses were documented.
      CONCLUSION: RPR 109881A was found to be a well-tolerated and promising taxoid
      agent. The MTD was 75 mg/m(2), and the recommended dose for phase II study was 60
      mg/m(2) as a 1-hour infusion every 3 weeks.

PMID- 10963646
TI  - Selective estrogen receptor modulators: structure, function, and clinical use.
AB  - The sex hormone estrogen is important for many physiologic processes. Prolonged
      stimulation of breast ductal epithelium by estrogen, however, can contribute to
      the development and progression of breast cancer, and treatments designed to
      block estrogen's effects are important options in the clinic. Tamoxifen and other
      similar drugs are effective in breast cancer prevention and treatment by
      inhibiting the proliferative effects of estrogen that are mediated through the
      estrogen receptor (ER). However, these drugs also have many estrogenic effects
      depending on the tissue and gene, and they are more appropriately called
      selective estrogen receptor modulators (SERMs). SERMs bind ER, alter receptor
      conformation, and facilitate binding of coregulatory proteins that activate or
      repress transcriptional activation of estrogen target genes. Theoretically, SERMs
      could be synthesized that would exhibit nearly complete agonist activity on the
      one hand or pure antiestrogenic activity on the other. Depending on their
      functional activities, SERMs could then be developed for a variety of clinical
      uses, including prevention and treatment of osteoporosis, treatment and
      prevention of estrogen-regulated malignancies, and even for hormone replacement
      therapy. Tamoxifen is effective in patients with ER-positive metastatic breast
      cancer and in the adjuvant setting. The promising role for tamoxifen in ductal
      carcinoma-in-situ or for breast cancer prevention is evolving, and its use can be
      considered in certain patient groups. Other SERMs are in development, with the
      goal of reducing toxicity and/or improving efficacy, and future agents have the
      potential of providing a new paradigm for maintaining the health of women.

PMID- 10963647
TI  - Diagnostic dilemmas in oncology. Case 1. Melanoma metastatic to the testis.

PMID- 10963648
TI  - Diagnostic dilemmas in oncology. Case 2. Umbilical metastasis as the presenting
      symptom of non-cell lung cancer.

PMID- 10963649
TI  - Diagnostic dilemmas in oncology. Case 3. Metastatic ovarian cancer simulating
      colon cancer.

PMID- 10963650
TI  - Tell the children.

PMID- 10963651
TI  - Detection of circulating tumor by reverse transcriptase polymerase chain
      reaction.

PMID- 10963652
TI  - Kinetochore reproduction theory may explain rapid chromosome evolution.

PMID- 10963653
TI  - Switching on and off with RNA.

PMID- 10963654
TI  - Amiloride-sensitive sodium channels contribute to the woes of the flu.

PMID- 10963656
TI  - "Coarse" stability and bifurcation analysis using time-steppers: a reaction
      diffusion example.
AB  - Evolutionary, pattern forming partial differential equations (PDEs) are often
      derived as limiting descriptions of microscopic, kinetic theory-based models of
      molecular processes (e.g., reaction and diffusion). The PDE dynamic behavior can
      be probed through direct simulation (time integration) or, more systematically,
      through stability/bifurcation calculations; time-stepper-based approaches, like
      the Recursive Projection Method [Shroff, G. M. & Keller, H. B. (1993) SIAM J.
      Numer. Anal. 30, 1099-1120] provide an attractive framework for the latter. We
      demonstrate an adaptation of this approach that allows for a direct, effective
      ("coarse") bifurcation analysis of microscopic, kinetic-based models; this is
      illustrated through a comparative study of the FitzHugh-Nagumo PDE and of a
      corresponding Lattice-Boltzmann model.

PMID- 10963655
TI  - Importance of replication in microarray gene expression studies: statistical
      methods and evidence from repetitive cDNA hybridizations.
AB  - We present statistical methods for analyzing replicated cDNA microarray
      expression data and report the results of a controlled experiment. The study was
      conducted to investigate inherent variability in gene expression data and the
      extent to which replication in an experiment produces more consistent and
      reliable findings. We introduce a statistical model to describe the probability
      that mRNA is contained in the target sample tissue, converted to probe, and
      ultimately detected on the slide. We also introduce a method to analyze the
      combined data from all replicates. Of the 288 genes considered in this controlled
      experiment, 32 would be expected to produce strong hybridization signals because
      of the known presence of repetitive sequences within them. Results based on
      individual replicates, however, show that there are 55, 36, and 58 highly
      expressed genes in replicates 1, 2, and 3, respectively. On the other hand, an
      analysis by using the combined data from all 3 replicates reveals that only 2 of
      the 288 genes are incorrectly classified as expressed. Our experiment shows that
      any single microarray output is subject to substantial variability. By pooling
      data from replicates, we can provide a more reliable analysis of gene expression
      data. Therefore, we conclude that designing experiments with replications will
      greatly reduce misclassification rates. We recommend that at least three
      replicates be used in designing experiments by using cDNA microarrays,
      particularly when gene expression data from single specimens are being analyzed.

PMID- 10963657
TI  - Self-similar intermediate asymptotics for a degenerate parabolic filtration
      absorption equation.
AB  - The equation partial differential(t)u = u partial differential(xx)(2)u -(c-1)(
      partial differential(x)u)(2) is known in literature as a qualitative mathematical
      model of some biological phenomena. Here this equation is derived as a model of
      the groundwater flow in a water-absorbing fissurized porous rock; therefore, we
      refer to this equation as a filtration-absorption equation. A family of self
      similar solutions to this equation is constructed. Numerical investigation of the
      evolution of non-self-similar solutions to the Cauchy problems having compactly
      supported initial conditions is performed. Numerical experiments indicate that
      the self-similar solutions obtained represent intermediate asymptotics of a wider
      class of solutions when the influence of details of the initial conditions
      disappears but the solution is still far from the ultimate state: identical zero.
      An open problem caused by the nonuniqueness of the solution of the Cauchy problem
      is discussed.

PMID- 10963659
TI  - The mechanical properties of Saccharomyces cerevisiae.
AB  - Cell-wall mechanical properties play an integral part in the growth and form of
      Saccharomyces cerevisiae. In contrast to the tremendous knowledge on the genetics
      of S. cerevisiae, almost nothing is known about its mechanical properties. We
      have developed a micromanipulation technique to measure the force required to
      burst single cells and have recently established a mathematical model to extract
      the mechanical properties of the cell wall from such data. Here we determine the
      average surface modulus of the S. cerevisiae cell wall to be 11.1 +/- 0.6 N/m and
      12.9 +/- 0.7 N/m in exponential and stationary phases, respectively, giving
      corresponding Young's moduli of 112 +/- 6 MPa and 107 +/- 6 MPa. This result
      demonstrates that yeast cell populations strengthen as they enter stationary
      phase by increasing wall thickness and hence the surface modulus, without
      altering the average elastic properties of the cell-wall material. We also
      determined the average breaking strain of the cell wall to be 82% +/- 3% in
      exponential phase and 80% +/- 3% in stationary phase. This finding provides a
      failure criterion that can be used to predict when applied stresses (e.g.,
      because of fluid flow) will lead to wall rupture. This work analyzes yeast
      compression experiments in different growth phases by using engineering
      methodology.

PMID- 10963658
TI  - Scanning electrochemical microscopy of living cells: different redox activities
      of nonmetastatic and metastatic human breast cells.
AB  - Electrochemical methods have been widely used to monitor physiologically
      important molecules in biological systems. This report describes the first
      application of the scanning electrochemical microscope (SECM) to probe the redox
      activity of individual living cells. The possibilities of measuring the rate and
      investigating the pathway of transmembrane charge transfer are demonstrated. By
      this approach, significant differences are detected in the redox responses given
      by nonmotile, nontransformed human breast epithelial cells, breast cells with a
      high level of motility (engendered by overexpression of protein kinase Calpha),
      and highly metastatic breast cancer cells. SECM analysis of the three cell lines
      reveals reproducible differences with respect to the kinetics of charge transfer
      by several redox mediators.

PMID- 10963660
TI  - Free entropy and property T factors.
AB  - We show that a large class of finite factors has free entropy dimension less than
      or equal to one. This class includes all prime factors and many property T
      factors.

PMID- 10963661
TI  - Structural evidence for a programmed general base in the active site of a
      catalytic antibody.
AB  - The crystal structure of the complex of a catalytic antibody with its cationic
      hapten at 1.9-A resolution demonstrates that the hapten amidinium group is
      stabilized through an ionic pair interaction with the carboxylate of a combining
      site residue. The location of this carboxylate allows it to act as a general base
      in an allylic rearrangement. When compared with structures of other antibody
      complexes in which the positive moiety of the hapten is stabilized mostly by
      cation-pi interactions, this structure shows that the amidinium moiety is a
      useful candidate to elicit a carboxylate in an antibody combining site at a
      predetermined location with respect to the hapten. More generally, this structure
      highlights the advantage of a bidentate hapten for the programmed positioning of
      a chemically reactive residue in an antibody through charge complementarity to
      the hapten.

PMID- 10963662
TI  - The importance of reactant positioning in enzyme catalysis: a hybrid quantum
      mechanics/molecular mechanics study of a haloalkane dehalogenase.
AB  - Hybrid quantum mechanics/molecular mechanics calculations using Austin Model 1
      system-specific parameters were performed to study the S(N)2 displacement
      reaction of chloride from 1,2-dichloroethane (DCE) by nucleophilic attack of the
      carboxylate of acetate in the gas phase and by Asp-124 in the active site of
      haloalkane dehalogenase from Xanthobacter autotrophicus GJ10. The activation
      barrier for nucleophilic attack of acetate on DCE depends greatly on the
      reactants having a geometry resembling that in the enzyme or an optimized gas
      phase structure. It was found in the gas-phase calculations that the activation
      barrier is 9 kcal/mol lower when dihedral constraints are used to restrict the
      carboxylate nucleophile geometry to that in the enzyme relative to the geometries
      for the reactants without dihedral constraints. The calculated quantum
      mechanics/molecular mechanics activation barriers for the enzymatic reaction are
      16.2 and 19.4 kcal/mol when the geometry of the reactants is in a near attack
      conformer from molecular dynamics and in a conformer similar to the crystal
      structure (DCE is gauche), respectively. This haloalkane dehalogenase lowers the
      activation barrier for dehalogenation of DCE by 2-4 kcal/mol relative to the
      single point energies of the enzyme's quantum mechanics atoms in the gas phase.
      S(N)2 displacements of this sort in water are infinitely slower than in the gas
      phase. The modest lowering of the activation barrier by the enzyme relative to
      the reaction in the gas phase is consistent with mutation experiments.

PMID- 10963663
TI  - Solvent dependence of dynamic transitions in protein solutions.
AB  - A transition as a function of increasing temperature from harmonic to anharmonic
      dynamics has been observed in globular proteins by using spectroscopic,
      scattering, and computer simulation techniques. We present here results of a
      dynamic neutron scattering analysis of the solvent dependence of the picosecond
      time scale dynamic transition behavior of solutions of a simple single-subunit
      enzyme, xylanase. The protein is examined in powder form, in D(2)O, and in four
      two-component perdeuterated single-phase cryosolvents in which it is active and
      stable. The scattering profiles of the mixed solvent systems in the absence of
      protein are also determined. The general features of the dynamic transition
      behavior of the protein solutions follow those of the solvents. The dynamic
      transition in all of the mixed cryosolvent-protein systems is much more gradual
      than in pure D(2)O, consistent with a distribution of energy barriers. The
      differences between the dynamic behaviors of the various cryosolvent protein
      solutions themselves are remarkably small. The results are consistent with a
      picture in which the picosecond-time scale atomic dynamics respond strongly to
      melting of pure water solvent but are relatively invariant in cryosolvents of
      differing compositions and melting points.

PMID- 10963664
TI  - Unbinding forces of single antibody-antigen complexes correlate with their
      thermal dissociation rates.
AB  - Point mutants of three unrelated antifluorescein antibodies were constructed to
      obtain nine different single-chain Fv fragments, whose on-rates, off-rates, and
      equilibrium binding affinities were determined in solution. Additionally,
      activation energies for unbinding were estimated from the temperature dependence
      of the off-rate in solution. Loading rate-dependent unbinding forces were
      determined for single molecules by atomic force microscopy, which extrapolated at
      zero force to a value close to the off-rate measured in solution, without any
      indication for multiple transition states. The measured unbinding forces of all
      nine mutants correlated well with the off-rate in solution, but not with the
      temperature dependence of the reaction, indicating that the same transition state
      must be crossed in spontaneous and forced unbinding and that the unbinding path
      under load cannot be too different from the one at zero force. The distance of
      the transition state from the ground state along the unbinding pathway is
      directly proportional to the barrier height, regardless of the details of the
      binding site, which most likely reflects the elasticity of the protein in the
      unbinding process. Atomic force microscopy thus can be a valuable tool for the
      characterization of solution properties of protein-ligand systems at the single
      molecule level, predicting relative off-rates, potentially of great value for
      combinatorial chemistry and biology.

PMID- 10963665
TI  - A role for alpha-and beta-catenins in bacterial uptake.
AB  - Interaction of internalin with E-cadherin promotes entry of Listeria
      monocytogenes into human epithelial cells. This process requires actin
      cytoskeleton rearrangements. Here we show, by using a series of stably
      transfected cell lines expressing E-cadherin variants, that the ectodomain of E
      cadherin is sufficient for bacterial adherence and that the intracytoplasmic
      domain is required for entry. The critical cytoplasmic region was further mapped
      to the beta-catenin binding domain. Because beta-catenin is known to interact
      with alpha-catenin, which binds to actin, we generated a fusion molecule
      consisting of the ectodomain of E-cadherin and the actin binding site of alpha
      catenin. Cells expressing this chimera were as permissive as E-cadherin
      expressing cells. In agreement with these data, alpha- and beta-catenins as well
      as E-cadherin clustered and colocalized at the entry site, where F-actin then
      accumulated. Taken together, these results reveal that E-cadherin, via beta- and
      alpha-catenins, can trigger dynamic events of actin polymerization and membrane
      extensions culminating in bacterial uptake.

PMID- 10963666
TI  - How well can an amoeba climb?
AB  - We report here our efforts to measure the crawling force generated by cells
      undergoing amoeboid locomotion. In a centrifuge microscope, acceleration was
      increased until amoebae of Dictyostelium discoideum were "stalled" or no longer
      able to "climb up." The "apparent weight" of the amoebae at stalling rpm in
      myosin mutants depended on the presence of myosin II (but not myosins IA and IB)
      and paralleled the cortical strength of the cells. Surprisingly, however, the
      cell stalled not only in low-density media as expected but also in media with
      densities greater than the cell density where the buoyant force should push the
      amoeba upward. We find that the leading pseudopod is bent under centrifugal force
      in all stalled amoebae, suggesting that this pseudopod is very dense indeed. This
      finding also suggests that directional cell locomotion against resistive forces
      requires a turgid forward-pointing pseudopod, most likely sustained by cortical
      actomyosin II.

PMID- 10963667
TI  - A role for Timeless in epithelial morphogenesis during kidney development.
AB  - Central to the process of epithelial organogenesis is branching morphogenesis
      into tubules and ducts. In the kidney, this can be modeled by a very simple
      system consisting of isolated ureteric bud (UB) cells, which undergo branching
      morphogenesis in response to soluble factors present in the conditioned medium of
      a metanephric mesenchyme cell line. By employing a targeted screen to identify
      transcription factors involved early in the morphogenetic program leading to UB
      branching, we identified the mammalian ortholog of Timeless (mTim) as a potential
      immediate early gene (IEG) important in this process. In the embryo, mTim was
      found to be expressed in patterns very suggestive of a role in epithelial
      organogenesis with high levels of expression in the developing lung, liver, and
      kidney, as well as neuroepithelium. In the embryonic kidney, the expression of
      mTim was maximal in regions of active UB branching, and a shift from the large
      isoform of mTim to a smaller isoform occurred as the kidney developed. Selective
      down-regulation of mTim resulted in profound inhibition of embryonic kidney
      growth and UB morphogenesis in organ culture. A direct effect on the branching UB
      was supported by the observation that down-regulation of mTim in the isolated UB
      (cultured in the absence of mesenchyme) resulted in marked inhibition of
      morphogenesis, suggesting a key role for Tim in the epithelial cell morphogenetic
      pathway leading to the formation of branching tubules.

PMID- 10963668
TI  - Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte
      expansion and differentiation during mouse development.
AB  - Wnt1 signaling has been implicated as one factor involved in neural crest-derived
      melanocyte (NC-M) development. Mice deficient for both Wnt1 and Wnt3a have a
      marked deficiency in trunk neural crest derivatives including NC-Ms. We have used
      cell lineage-directed gene targeting of Wnt signaling genes to examine the
      effects of Wnt signaling in mouse neural crest development. Gene expression was
      directed to cell lineages by infection with subgroup A avian leukosis virus
      vectors in lines of transgenic mice that express the retrovirus receptor tv-a.
      Transgenic mice with tva in either nestin-expressing neural precursor cells (line
      Ntva) or dopachrome tautomerase (DCT)-expressing melanoblasts (line DCTtva) were
      analyzed. We overstimulated Wnt signaling in two ways: directed gene transfer of
      Wnt1 to Ntva(+) cells and transfer of beta-catenin to DCTtva(+) NC-M precursor
      cells. In both methods, NC-M expansion and differentiation were effected.
      Significant increases were observed in the number of NC-Ms [melanin(+) and
      tyrosinase-related protein 1 (TYRP1)(+) cells], the differentiation of melanin(-)
      TYRP1(+) cells to melanin(+) TYRP1(+) NC-Ms, and the intensity of pigmentation
      per NC-M. These data are consistent with Wnt1 signaling being involved in both
      expansion and differentiation of migrating NC-Ms in the developing mouse embryo.
      The use of lineage-directed gene targeting will allow the dissection of signaling
      molecules involved in NC development and is adaptable to other mammalian
      developmental systems.

PMID- 10963669
TI  - Anthropoid humeri from the late Eocene of Egypt.
AB  - A number of recent studies have, by necessity, placed a great deal of emphasis on
      the dental evidence for Paleogene anthropoid interrelationships, but cladistic
      analyses of these data have led to the erection of phylogenetic hypotheses that
      appear to be at odds with biogeographic and stratigraphic considerations.
      Additional morphological data from the cranium and postcranium of certain poorly
      understood Paleogene primates are clearly needed to help test whether such
      hypotheses are tenable. Here we describe humeri attributable to Proteopithecus
      sylviae and Catopithecus browni, two anthropoids from late Eocene sediments of
      the Fayum Depression in Egypt. Qualitative and morphometric analyses of these
      elements indicate that humeri of the oligopithecine Catopithecus are more similar
      to early Oligocene propliopithecines than they are to any other Paleogene
      anthropoid taxon, and that Proteopithecus exhibits humeral similarities to
      parapithecids that may be symplesiomorphies of extant (or "crown") Anthropoidea.
      The humeral morphology of Catopithecus is consistent with certain narrowly
      distributed dental apomorphies-such as the loss of the upper and lower second
      premolar and the development of a honing blade for the upper canine on the lower
      third premolar-which suggest that oligopithecines constitute the sister group of
      a clade containing propliopithecines and Miocene-Recent catarrhines and are not
      most closely related to Proteopithecus as has recently been proposed.

PMID- 10963670
TI  - Functions of the DNA damage response pathway target Ho endonuclease of yeast for
      degradation via the ubiquitin-26S proteasome system.
AB  - Ho endonuclease of Saccharomyces cerevisiae is a homing endonuclease that makes a
      site-specific double-strand break in the MAT gene in late G(1). Here we show that
      Ho is rapidly degraded via the ubiquitin-26S proteasome system through two
      ubiquitin-conjugating enzymes UBC2(Rad6) and UBC3(Cdc34). UBC2(Rad6) is complexed
      with the ring finger DNA-binding protein Rad18, and we find that Ho is stabilized
      in rad18 mutants. We show that the Ho degradation pathway involving UBC3(Cdc34)
      goes through the Skp1/Cdc53/F-box (SCF) ubiquitin ligase complex and identify a F
      box protein, Yml088w, that is required for Ho degradation. Components of a
      defined pathway of the DNA damage response, MEC1, RAD9, and CHK1, are also
      necessary for Ho degradation, whereas functions of the RAD24 epistasis group and
      the downstream effector RAD53 have no role in degradation of Ho. Our results
      indicate a link between the endonuclease function of Ho and its destruction.

PMID- 10963671
TI  - The MITE family heartbreaker (Hbr): molecular markers in maize.
AB  - Transposable elements are ubiquitous in plant genomes, where they frequently
      comprise the majority of genomic DNA. The maize genome, which is believed to be
      structurally representative of large plant genomes, contains single genes or
      small gene islands interspersed with much longer blocks of retrotransposons.
      Given this organization, it would be desirable to identify molecular markers
      preferentially located in genic regions. In this report, the features of a newly
      described family of miniature inverted repeat transposable elements (MITEs)
      (called Heartbreaker), including high copy number and polymorphism, stability,
      and preference for genic regions, have been exploited in the development of a
      class of molecular markers for maize. To this end, a modification of the AFLP
      procedure called transposon display was used to generate and display hundreds of
      genomic fragments anchored in Hbr elements. An average of 52 markers were
      amplified for each primer combination tested. In all, 213 polymorphic fragments
      were reliably scored and mapped in 100 recombinant inbred lines derived from a
      cross between the maize inbreds B73 x Mo17. In this mapping population, Hbr
      markers are distributed evenly across the 10 maize chromosomes. This procedure
      should be of general use in the development of markers for other MITE families in
      maize and in other plant and animal species where MITEs have been identified.

PMID- 10963672
TI  - Normal cardiovascular development in mice deficient for 16 genes in 550 kb of the
      velocardiofacial/DiGeorge syndrome region.
AB  - Hemizygous interstitial deletions in human chromosome 22q11 are associated with
      velocardiofacial syndrome and DiGeorge syndrome and lead to multiple congenital
      abnormalities, including cardiovascular defects. The gene(s) responsible for
      these disorders is thought to reside in a 1.5-Mb region of 22q11 in which 27
      genes have been identified. We have used Cre-mediated recombination of LoxP sites
      in embryonic stem cells and mice to generate a 550-kb deletion encompassing 16 of
      these genes in the corresponding region on mouse chromosome 16. Mice heterozygous
      for this deletion are normal and do not exhibit cardiovascular abnormalities.
      Because mice with a larger deletion on mouse chromosome 16 do have heart defects,
      the results allow us to exclude these 16 genes as being solely, or in combination
      among themselves, responsible for the cardiovascular abnormalities in
      velocardiofacial/DiGeorge syndrome. We also generated mice with a duplication of
      the 16 genes that may help dissect the genetic basis of "cat eye" and derivative
      22 syndromes that are characterized by extra copies of portions of 22q11,
      including these 16 genes. We also describe a strategy for selecting cell lines
      with defined chromosomal rearrangements. The method is based on reconstitution of
      a dominant selection marker after Cre-mediated recombination of LoxP sites.
      Therefore it should be widely applicable to many cell lines.

PMID- 10963673
TI  - Singular value decomposition for genome-wide expression data processing and
      modeling.
AB  - We describe the use of singular value decomposition in transforming genome-wide
      expression data from genes x arrays space to reduced diagonalized "eigengenes" x
      "eigenarrays" space, where the eigengenes (or eigenarrays) are unique orthonormal
      superpositions of the genes (or arrays). Normalizing the data by filtering out
      the eigengenes (and eigenarrays) that are inferred to represent noise or
      experimental artifacts enables meaningful comparison of the expression of
      different genes across different arrays in different experiments. Sorting the
      data according to the eigengenes and eigenarrays gives a global picture of the
      dynamics of gene expression, in which individual genes and arrays appear to be
      classified into groups of similar regulation and function, or similar cellular
      state and biological phenotype, respectively. After normalization and sorting,
      the significant eigengenes and eigenarrays can be associated with observed genome
      wide effects of regulators, or with measured samples, in which these regulators
      are overactive or underactive, respectively.

PMID- 10963674
TI  - Virus neutralization by germ-line vs. hypermutated antibodies.
AB  - Mice infected with vesicular stomatitis virus (VSV), a cytopathic virus closely
      related to rabies virus, mount a virus-neutralizing antibody response protecting
      against lethal disease. VSVneutralizing monoclonal IgGs isolated from primary
      immune responses were devoid of somatic mutations, whereas most secondary and all
      hyperimmune response IgGs tested were hypermutated. A comparative analysis of
      recombinant single-chain antibody fragments (scFv-Ckappa) revealed that even the
      germ-line precursor of one hypermutated antibody bound and neutralized VSV. Four
      somatic amino acid substitutions in V(H) increased by 300-fold the binding
      strength of monovalent scFv-Ckappa. The multivalent binding avidity of germ-line
      scFv-Ckappa was increased by more than 10-fold compared with the monovalent
      binding strength. In contrast, hypermutated scFv-Ckappa did not show such avidity
      effects. Thus the overall binding difference between the germ-line and the
      hypermutated VSV-neutralizing antibody was only 10- to 15-fold. This may explain
      why primary germ-line antibodies and secondary hypermutated antibodies directed
      against pathogens such as viruses and bacteria expressing repetitive antibody
      determinants show rather similar binding qualities, whereas monovalently binding
      hapten-specific antibodies can show "affinity maturation" effects of up to 1000
      fold.

PMID- 10963675
TI  - Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid
      organogenesis and controls apoptosis during thymopoiesis.
AB  - To identify the physiological functions of the retinoid-related orphan receptor
      gamma (RORgamma), a member of the nuclear receptor superfamily, mice deficient in
      RORgamma function were generated by targeted disruption. RORgamma(-/-) mice lack
      peripheral and mesenteric lymph nodes and Peyer's patches, indicating that
      RORgamma expression is indispensable for lymph node organogenesis. Although the
      spleen is enlarged, its architecture is normal. The number of peripheral blood
      CD3(+) and CD4(+) lymphocytes is reduced 6- and 10-fold, respectively, whereas
      the number of circulating B cells is normal. The thymus of RORgamma(-/-) mice
      contains 74.4% +/- 8.9% fewer thymocytes than that of wild-type mice. Flow
      cytometric analysis showed a decrease in the CD4(+)CD8(+) subpopulation. Terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining
      demonstrated a 4-fold increase in apoptotic cells in the cortex of the thymus of
      RORgamma(-/-) mice. The latter was supported by the observed increase in annexin
      V-positive cells. RORgamma(-/-) thymocytes placed in culture exhibit a dramatic
      increase in the rate of "spontaneous" apoptosis. This increase is largely
      associated with CD4(+)CD8(+) thymocytes and may, at least in part, be related to
      the greatly reduced level of expression of the anti-apoptotic gene Bcl-X(L). Flow
      cytometric analysis demonstrated a 6-fold rise in the percentage of cells in the
      S phase of the cell cycle among thymocytes from RORgamma(-/-) mice. Our
      observations indicate that RORgamma is essential for lymphoid organogenesis and
      plays an important regulatory role in thymopoiesis. Our findings support a model
      in which RORgamma negatively controls apoptosis in thymocytes.

PMID- 10963676
TI  - A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T
      cell activation.
AB  - Transmembrane protein tyrosine phosphatases, such as CD45, can act as both
      positive and negative regulators of cellular signaling. CD45 positively modulates
      T cell receptor (TCR) signaling by constitutively priming p56lck through the
      dephosphorylation of the C-terminal negative regulatory phosphotyrosine site.
      However, CD45 can also exert negative effects on cellular processes, including
      events triggered by integrin-mediated adhesion. To better understand these
      opposing actions of tyrosine phosphatases, the subcellular compartmentalization
      of CD45 was imaged by using laser scanning confocal microscopy during functional
      TCR signaling of live T lymphocytes. On antigen engagement, CD45 was first
      excluded from the central region of the interface between the T cell and the
      antigen-presenting surface where CD45 would inhibit integrin activation.
      Subsequently, CD45 was recruited back to the center of the contact to an area
      adjacent to the site of sustained TCR engagement. Thus, CD45 is well positioned
      within a supramolecular assembly in the vicinity of the engaged TCR, where CD45
      would be able to maintain src-kinase activity for the duration of TCR engagement.

PMID- 10963677
TI  - The vav exchange factor is an essential regulator in actin-dependent receptor
      translocation to the lymphocyte-antigen-presenting cell interface.
AB  - During the interaction of a T cell with an antigen-presenting cell (APC), several
      receptor ligand pairs, including the T cell receptor (TCR)/major
      histocompatibility complex (MHC), accumulate at the T cell/APC interface in
      defined geometrical patterns. This accumulation depends on a movement of the T
      cell cortical actin cytoskeleton toward the interface. Here we study the
      involvement of the guanine nucleotide exchange factor vav in this process. We
      crossed 129 vav(-/-) mice with B10/BR 5C.C7 TCR transgenic mice and used peptide
      loaded APCs to stimulate T cells from the offspring. We found that the
      accumulation of TCR/MHC at the T cell/APC interface and the T cell actin
      cytoskeleton rearrangement were clearly defective in these vav(+/-) mice. A
      comparable defect in superantigen-mediated T cell activation of T cells from non
      TCR transgenic 129 mice was also observed, although in this case it was more
      apparent in vav(-/-) mice. These data indicate that vav is an essential regulator
      of cytoskeletal rearrangements during T cell activation.

PMID- 10963678
TI  - Structural requirements for antigen presentation by mouse CD1.
AB  - The structural basis for the T cell response to glycolipid antigens (Ags) remains
      poorly understood. T lymphocytes autoreactive for mouse CD1 (mCD1.1) or reactive
      for the glycosphingolipid alphagalactosylceramide (alpha-GalCer) presented by
      mCD1.1 have been described previously. In this paper it is shown that mutations
      at the top of the alpha helices and in the bottom of the Ag-binding groove can
      disrupt both mCD1.1 autoreactivity and alpha-GalCer recognition. The locations of
      the positions that affect T cell responses indicate that recognition of mCD1.1 is
      not likely to be unconventional or superantigen-like. Furthermore, the effects of
      the bottom of the pocket mutation suggest that the autoreactive response could
      require an autologous ligand, and they indicate that alpha-GalCer binds to the
      groove of mCD1.1, most likely with the shorter 18-carbon hydrophobic chain in the
      A' pocket. Natural killer T cell hybridomas with identical T cell antigen
      receptor (TCR) alpha chains and different beta chains respond differently to
      alpha-GalCer presented by mCD1.1 mutants. This finding indicates a role for TCR
      beta in defining natural killer T cell specificity, despite the more restricted
      diversity of the alpha chains in these cells. Overall, the data are consistent
      with a mode of lipoglycan recognition similar to that proposed for glycopeptides,
      in which the TCR alpha and beta chains survey a surface composed of both mCD1.1
      and the carbohydrate portion of alpha-GalCer.

PMID- 10963679
TI  - Genetic influence on the structural variations of the abnormal prion protein.
AB  - Prion diseases are characterized by the presence of the abnormal prion protein
      PrP(Sc), which is believed to be generated by the conversion of the alpha-helical
      structure that predominates in the normal PrP isoform into a beta-sheet structure
      resistant to proteinase K (PK). In human prion diseases, two major types of
      PrP(Sc), type 1 and 2, can be distinguished based on the difference in
      electrophoretic migration of the PK-resistant core fragment. In this study,
      protein sequencing was used to identify the PK cleavage sites of PrP(Sc) in 36
      cases of prion diseases. We demonstrated two primary cleavage sites at residue 82
      and residue 97 for type 1 and type 2 PrP(Sc), respectively, and numerous
      secondary cleavages distributed along the region spanning residues 74-102.
      Accordingly, we identify three regions in PrP(Sc): one N-terminal (residues 23
      73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is
      invariably PK-resistant, and a third variable region (residues 74-102) where the
      site of the PK cleavage, likely reflecting the extent of the beta-sheet
      structure, varies mostly as a function of the PrP genotype at codon 129.

PMID- 10963680
TI  - Androgen-induced proliferative quiescence in prostate cancer cells: the role of
      AS3 as its mediator.
AB  - In the prostate gland of adult mammals, most epithelial cells are in a state of
      proliferative quiescence. Androgens regulate this effect by inducing cell cycle
      arrest in the G(0)/G(1) phase. Potential mediators of this androgen-induced
      proliferative shutoff were identified by means of subtracted cDNA libraries. The
      expression pattern of one of these sequences, AS3, strongly correlated with the
      expression of the androgen-induced proliferative shutoff both temporally and
      dosewise. The AS3 gene is located on chromosome 13 q12.3, in close proximity to
      the BRCA2 gene. The loss of chromosomal regions where AS3 alleles are located
      correlates with various human cancers, including prostate. The biological effect
      of AS3 was tested in two stable cell lines, one expressing sense and another
      expressing antisense AS3 constructs, both under tetracycline regulation. S9 cells
      were obtained by retroviral infection with virions containing a tetracycline
      regulated sense AS3 construct. In these cells, sense AS3 was negatively regulated
      by tetracycline. Tetracycline withdrawal increased the expression of AS3 mRNA and
      protein. The expression of tetracycline-regulated AS3 resulted in inhibition of
      cell proliferation. A4 cells were obtained by retroviral infection with virions
      containing a tetracycline-regulated antisense AS3 construct. Vector-driven
      expression of antisense-AS3 blocked the induction of androgen-induced endogenous
      AS3 mRNA and blocked the inhibitory effect of androgens on cell proliferation.
      Tetracycline-regulated expression of the empty vector control had no effect on
      cell proliferation. These experiments strongly suggest that AS3 is a mediator of
      the androgen-induced proliferative shutoff.

PMID- 10963681
TI  - Genetic footprinting with mariner-based transposition in Pseudomonas aeruginosa.
AB  - The complete DNA sequence of Pseudomonas aeruginosa provides an opportunity to
      apply functional genomics to a major human pathogen. A comparative genomics
      approach combined with genetic footprinting was used as a strategy to identify
      genes required for viability in P. aeruginosa. Use of a highly efficient in vivo
      mariner transposition system in P. aeruginosa facilitated the analysis of
      candidate genes of this class. We have developed a rapid and efficient allelic
      exchange system by using the I-SceI homing endonuclease in conjunction with in
      vitro mariner mutagenesis to generate mutants within targeted regions of the P.
      aeruginosa chromosome for genetic footprinting analyses. This technique for
      generating transposon insertion mutants should be widely applicable to other
      organisms that are not naturally transformable or may lack well developed in vivo
      transposition systems. We tested this system with three genes in P. aeruginosa
      that have putative essential homologs in Haemophilus influenzae. We show that one
      of three H. influenzae essential gene homologs is needed for growth in P.
      aeruginosa, validating the practicality of this comparative genomics strategy to
      identify essential genes in P. aeruginosa.

PMID- 10963682
TI  - Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of
      ischemic preconditioning in conscious rabbits.
AB  - We examined the role of cyclooxygenase-2 (COX-2) in the late phase of ischemic
      preconditioning (PC). A total of 176 conscious rabbits were used. Ischemic PC
      (six cycles of 4-min coronary occlusions/4-min reperfusions) resulted in a rapid
      increase in myocardial COX-2 mRNA levels (+231 +/- 64% at 1 h; RNase protection
      assay) followed 24 h later by an increase in COX-2 protein expression (+216 +/-
      79%; Western blotting) and in the myocardial content of prostaglandin (PG)E(2)
      and 6-keto-PGF(1alpha) (+250 +/- 85% and +259 +/- 107%, respectively; enzyme
      immunoassay). Administration of two unrelated COX-2 selective inhibitors (NS-398
      and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase
      in tissue levels of PGE(2) and 6-keto-PGF(1alpha). The same doses of NS-398 and
      celecoxib, given 24 h after ischemic PC, completely blocked the cardioprotective
      effects of late PC against both myocardial stunning and myocardial infarction,
      indicating that COX-2 activity is necessary for this phenomenon to occur. Neither
      NS-398 nor celecoxib lowered PGE(2) or 6-keto-PGF(1alpha) levels in the
      nonischemic region of preconditioned rabbits, indicating that constitutive COX-1
      activity was unaffected. Taken together, these results demonstrate that, in
      conscious rabbits, up-regulation of COX-2 plays an essential role in the
      cardioprotection afforded by the late phase of ischemic PC. Therefore, this study
      identifies COX-2 as a cardioprotective protein. The analysis of arachidonic acid
      metabolites strongly points to PGE(2) and/or PGI(2) as the likely effectors of
      COX-2-dependent protection. The recognition that COX-2 mediates the antistunning
      and antiinfarct effects of late PC impels a reassessment of current views
      regarding this enzyme, which is generally regarded as detrimental.

PMID- 10963683
TI  - Establishment of an animal-bacterial association: recruiting symbiotic vibrios
      from the environment.
AB  - While most animal-bacterial symbioses are reestablished each successive
      generation, the mechanisms by which the host and its potential microbial partners
      ensure tissue colonization remain largely undescribed. We used the model
      association between the squid Euprymna scolopes and Vibrio fischeri to examine
      this process. This light organ symbiosis is initiated when V. fischeri cells
      present in the surrounding seawater enter pores on the surface of the nascent
      organ and colonize deep epithelia-lined crypts. We discovered that when newly
      hatched squid were experimentally exposed to natural seawater, the animals
      responded by secreting a viscous material from the pores of the organ. Animals
      maintained in filtered seawater produced no secretions unless Gram-negative
      bacteria, either living or dead, were reintroduced. The viscous material bound
      only lectins that are specific for either N-acetylneuraminic acid or N
      acetylgalactosamine, suggesting that it was composed of a mucus-containing
      matrix. Complex ciliated fields on the surface of the organ produced water
      currents that focused the matrix into a mass that was tethered to, and suspended
      above, the light organ pores. When V. fischeri cells were introduced into the
      seawater surrounding the squid, the bacteria were drawn into its fluid-filled
      body cavity during ventilation and were captured in the matrix. After residing as
      an aggregate for several hours, the symbionts migrated into the pores and
      colonized the crypt epithelia. This mode of infection may be an example of a
      widespread strategy by which aquatic hosts increase the likelihood of successful
      colonization by rarely encountered symbionts.

PMID- 10963685
TI  - Species-barrier-independent prion replication in apparently resistant species.
AB  - Transmission of prions between mammalian species is thought to be limited by a
      "species barrier," which depends on differences in the primary structure of prion
      proteins in the infecting inoculum and the host. Here we demonstrate that a
      strain of hamster prions thought to be nonpathogenic for conventional mice leads
      to prion replication to high levels in such mice but without causing clinical
      disease. Prions pathogenic in both mice and hamsters are produced. These results
      demonstrate the existence of subclinical forms of prion infection with important
      public health implications, both with respect to iatrogenic transmission from
      apparently healthy humans and dietary exposure to cattle and other species
      exposed to bovine spongiform encephalopathy prions. Current definitions of the
      species barrier, which have been based on clinical end-points, need to be
      fundamentally reassessed.

PMID- 10963684
TI  - Vascular endothelial growth factor: direct neuroprotective effect in in vitro
      ischemia.
AB  - Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic
      peptide with recently identified neurotrophic effects. Because some neurotrophic
      factors can protect neurons from hypoxic or ischemic injury, we investigated the
      possibility that VEGF has similar neuroprotective properties. In HN33, an
      immortalized hippocampal neuronal cell line, VEGF reduced cell death associated
      with an in vitro model of cerebral ischemia: at a maximally effective
      concentration of 50 ng/ml, VEGF approximately doubled the number of cells
      surviving after 24 h of hypoxia and glucose deprivation. To investigate the
      mechanism of neuroprotection by VEGF, the expression of known target receptors
      for VEGF was measured by Western blotting, which showed that HN33 cells expressed
      VEGFR-2 receptors and neuropilin-1, but not VEGFR-1 receptors. The neuropilin-1
      ligand placenta growth factor-2 failed to reproduce the protective effect of
      VEGF, pointing to VEGFR-2 as the site of VEGF's neuroprotective action. Two
      phosphatidylinositol 3'-kinase inhibitors, wortmannin and LY294002, reversed the
      neuroprotective effect of VEGF, implicating the phosphatidylinositol 3'
      kinase/Akt signal transduction system in VEGF-mediated neuroprotection. VEGF also
      protected primary cultures of rat cerebral cortical neurons from hypoxia and
      glucose deprivation. We conclude that in addition to its known role as an
      angiogenic factor, VEGF may exert a direct neuroprotective effect in hypoxic
      ischemic injury.

PMID- 10963705
TI  - An analytical, numerical, and experimental comparison of the fluid velocity in
      the vicinity of an open tank with one and two lateral exhaust slot hoods and a
      uniform crossdraft.
AB  - The objective of this research was to compare mathematical models of the fluid
      velocity in the vicinity of an open tank with lateral slot exhaust. Two
      approaches were explored: a numerical solution assuming turbulent flow and an
      analytical solution assuming potential flow. A numerical simulation of the flow
      field in and around an open surface tank was performed using the commercial
      software FLUENT. An analytical solution was obtained using two-dimensional
      potential fluid flow determined using the Schwarz-Christoffel transformation and
      complex potential theory. The numerical and analytical solutions were compared
      with numerical solutions and experimental measurements published by others. The
      numerical solution using FLUENT and the two numerical solutions published by
      others appear to reflect experimental conditions with equal accuracy. In some
      regions, the FLUENT solution appears better while in other regions the other two
      solutions appear better. Differences in geometry and boundary conditions could
      explain these differences. Greater differences were observed between the FLUENT
      and CFX-F3D solutions than between the EOL-2D and CFX-F3D solutions. This was
      unexpected since the geometry, boundary conditions, and turbulence model were
      more similar in the former case than in the latter. The potential flow solution,
      while simpler and less computationally intensive than the numerical solutions,
      resulted in estimates of experimental velocity that were equally as good as those
      of the numerical solutions. The simplicity and conservative estimates of this
      model make it useful for estimating exhaust hood flow fields.

PMID- 10963686
TI  - Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene
      structure, and sequence similarities to molybdenum cofactor-synthesizing and
      cytoskeleton-associated proteins.
AB  - Gephyrin is essential for both the postsynaptic localization of inhibitory
      neurotransmitter receptors in the central nervous system and the biosynthesis of
      the molybdenum cofactor (Moco) in different peripheral organs. Several
      alternatively spliced gephyrin transcripts have been identified in rat brain that
      differ in their 5' coding regions. Here, we describe gephyrin splice variants
      that are differentially expressed in non-neuronal tissues and different regions
      of the adult mouse brain. Analysis of the murine gephyrin gene indicates a highly
      mosaic organization, with eight of its 29 exons corresponding to the
      alternatively spliced regions identified by cDNA sequencing. The N- and C
      terminal domains of gephyrin encoded by exons 3-7 and 16-29, respectively,
      display sequence similarities to bacterial, invertebrate, and plant proteins
      involved in Moco biosynthesis, whereas the central exons 8, 13, and 14 encode
      motifs that may mediate oligomerization and tubulin binding. Our data are
      consistent with gephyrin having evolved from a Moco biosynthetic protein by
      insertion of protein interaction sequences.

PMID- 10963687
TI  - Constitutive activation of tethered-peptide/corticotropin-releasing factor
      receptor chimeras.
AB  - Constitutive activity, or ligand-independent activity, of mutant G protein
      coupled receptors (GPCRs) has been described extensively and implicated in the
      pathology of many diseases. Using the corticotropin-releasing factor (CRF)
      receptor and the thrombin receptor as a model, we present a ligand-dependent
      constitutive activation of a GPCR. A chimera in which the N-terminal domain of
      the CRF receptor is replaced by the amino-terminal 16 residues of CRF displays
      significant levels of constitutive activation. The activity, as measured by
      intracellular levels of cAMP, is blocked in a dose-dependent manner by the
      nonpeptide antagonist antalarmin. These results support a propinquity effect in
      CRF receptor activation, in which the amino-terminal portion of the CRF peptide
      is presented to the body of the receptor in the proper proximity for activation.
      This form of ligand-dependent constitutive activation may be of general
      applicability for the creation of constitutively activated GPCRs that are
      regulated by peptide ligands such as CRF. These chimeras may prove useful in
      analyzing mechanisms of receptor regulation and in the structural analysis of
      ligand activated receptors.

PMID- 10963706
TI  - Potential exposure of amateurs (consumers) through painting wood preservative and
      antifoulant preparations.
AB  - Data are presented for work patterns, inhalation and potential dermal exposure
      for amateurs painting wood preservatives to garden structures, and antifoulants
      to leisure boats. The results are quoted as rates of in-use product deposition or
      time-weighted inhaled product concentrations. Quoting data in this general and
      normalized form enables predictive risk assessment. The product densities were
      assumed to be 1.0 gml(-1). Inhalation exposure was detected in about 40% of the
      surveys, being about 100 times higher for wood preservatives than for
      antifoulants. The maximum airborne wood preservative concentration was 8.03 mg m(
      3), measured over the period of painting (that is not an 8h time-weighted average
      value). Regarding potential dermal exposure, the processes are only broadly
      comparable. Most of the data appear to fall into relatively narrow distributions,
      with median values around 5 mg min(-1) (for preservatives) and around 16 mg min(
      1) (for antifoulants). About half of the deposit on clothing was found to occur
      below the waist. The data comparing gloved and bare hand working indicate that
      even simple gloves offer a degree of protection for skin.

PMID- 10963707
TI  - Comparison of four methods to assess fungal alpha-amylase in flour dust.
AB  - The aim of the study was to compare four different immunological methods to
      analyse fungal alpha-amylase in flour dust samples. Three European research
      groups have independently developed four immuno assay based methods to measure
      alpha-amylase in air samples. Three of the methods use polyclonal antibodies and
      one method uses monoclonal antibodies. Eighty personal samples have been
      collected during two to three work-shifts in four bakeries. Sampling was
      performed with PAS-6 inhalable dust samplers and aliquots from each sample were
      analysed by the three laboratories. The agreement between the four methods was
      high compared with agreement between immunological methods to measure other
      allergens in the air, e.g. for rat allergens. For the three methods with
      polyclonal antibodies the mean differences for individual samples was less than a
      factor of two. The arithmetic means (AM) of the estimated alpha-amylase exposure
      were 12.5, 11.3, 8.6 and 25.9ng/m(3) for the respective methods with values
      ranging from below the detection limit to 192, 215, 207 and 615 ng/m(3). The AM
      for all samples analysed by the methods with polyclonal antibodies varied by
      about a factor of 1.5. About one-third of the values were below or at the
      detection limit for all methods. In a regression analysis the squared correlation
      coefficients (R(2)) between the methods varied between 0.91 and 0.95 for the log
      transformed values. For workplace monitoring, results from the methods using
      polyclonal antibodies will be relatively comparable. High levels of alpha-amylase
      might differ in absolute numbers with a factor of two or more between the
      different methods but will anyway be considered as high and should result in
      preventive actions. On the other hand, this study also shows that despite the
      relative agreement between methods, there is a clear need for standardization.

PMID- 10963708
TI  - A survey of exposure to diesel engine exhaust emissions in the workplace.
AB  - Forty sites were visited during a survey of exposures to diesel engine exhaust
      emissions. Personal and background exposure to gaseous components, respirable
      dust, elemental carbon, organic carbon and total carbon were measured and details
      of control systems were recorded. The results show a wide spread in exposure
      patterns reflecting the different work practices, job categories of employees and
      the control methods used. However, sites where fork-lift trucks were in use
      consistently produced the highest exposures. The survey results suggest that the
      measurement of elemental carbon could be used as an indicator of exposure to
      diesel engine exhaust emissions.

PMID- 10963709
TI  - Heat exposure study in the workplace in a glass manufacturing unit in India.
AB  - The heat exposure for working conditions in coastal areas of tropical and
      subtropical countries like India is a crucial factor in improved qualitative and
      quantitative production. The hot climate augments the heat exposure close to
      sources like furnaces. In the present work heat exposure to workers in glass
      manufacturing units in a coastal area of India has been assessed. The Wet Bulb
      Globe Temperature (WBGT), the Corrected Effective Temperature (CET) and Mean
      Radiant Temperature (MRT) were measured. The WBGT values much exceeded ACGIH
      TLVs. A revision of these standards to suit tropical and subtropical conditions
      is required. The recommended durations of work and rest have been estimated.

PMID- 10963710
TI  - A study on dust emission, particle size distribution and formaldehyde
      concentration during machining of medium density fibreboard.
AB  - A study to characterise the quantity, particle size distribution and morphology
      of dust created during the machining of MDF was carried out. Four different types
      of MDF boards were included in this study, including a 'zero-formaldehyde' board
      that contains isocyanate-based resin, rather than urea-formaldehyde resin. In
      addition, natural softwood (pine) and natural hardwood (oak) were included in the
      study, for comparison with MDF. The results show that in general, the dust
      generated by machining MDF is comparable in terms of particle size distribution
      and morphology with the dust generated by similarly machining hardwood or
      softwood. The quantity of dust generated during sanding is higher for sanding MDF
      compared with sanding either hardwood or softwood. However, for sawing there is
      no significant difference between MDF and natural woods, in terms of the quantity
      of dust generated. Free formaldehyde in the air was less than 0.17mg m(-3) during
      machining of the Class B (higher formaldehyde potential) MDF board. There was no
      measurable isocyanate in the dust generated from the boards.

PMID- 10963711
TI  - Exposure to microbes, endotoxins and total dust in cigarette and cigar
      manufacturing: an evaluation of health hazards.
AB  - The concentrations of airborne microbes, endotoxins and total dust were measured
      in one cigar and two cigarette factories in order to evaluate the risk of
      respiratory symptoms. The role of humidifiers as a source of microbes was
      investigated. Air samples for the analyses were collected near workers' breathing
      zones during different phases of production. Gram-negative bacteria, mesophilic
      fungi, thermotolerant fungi and thermophilic actinomycetes, but not Aspergillus
      glaucus fungi, were found in higher concentrations in the cigar factory than in
      the cigarette factories. High microbe concentrations (10(4)-10(5)cfu m(-3))
      occurred throughout the production line in the cigar factory. The highest dust
      and endotoxin concentrations were found in the wick-making department in the
      cigar factory (3.3mg dust per m(3) and 38ng endotoxin per m(3)) and during the
      weighing or handling of raw tobacco in the cigarette factories (4.5 mg dust per
      m(3) and 106ng endotoxin per m(3)). The spray humidifiers in the cigar factory
      were a more important source of microbes than was raw tobacco. In the cigarette
      factories, steam humidifiers were used; the humidified air was free of microbes.
      The microbe concentrations in the tobacco factories were lower than in
      environments known to have caused allergic alveolitis.

PMID- 10963712
TI  - Beyond the job exposure matrix (JEM): the task exposure matrix (TEM).
AB  - The job exposure matrix (JEM) has been employed to assign cumulative exposure to
      workers in many epidemiological studies. In these studies, where quantitative
      data are available, all workers with the same job title and duration are usually
      assigned similar cumulative exposures, expressed in mgm(-3)xyears. However, if
      the job is composed of multiple tasks, each with its own specific exposure
      profile, then assigning all workers within a job the same mean exposure can lead
      to misclassification of exposure. This variability of exposure within job titles
      is one of the major weaknesses of JEMs. A method is presented for reducing the
      variability in the JEM methodology, which has been called the task exposure
      matrix (TEM). By summing the cumulative exposures of a worker over all the tasks
      worked within a job title, it is possible to address the variability of exposure
      within the job title, and reduce possible exposure misclassification. The
      construction of a TEM is outlined and its application in the context of a study
      in the primary aluminium industry is described. The TEM was found to assign
      significantly different cumulative exposures to the majority of workers in the
      study, compared with the JEM and the degree of difference in cumulative exposure
      between the JEM and the TEM varied greatly between contaminants.

PMID- 10963713
TI  - Antioxidants and cardiovascular disease; panaceas or tonics for tired sheep?

PMID- 10963714
TI  - Lipid peroxidation, antioxidants and cardiovascular disease: how should we move
      forward?

PMID- 10963715
TI  - Diet and prevention of coronary heart disease: the potential role of
      phytochemicals.
AB  - Epidemiological studies, and some clinical trials, demonstrate that a proper diet
      reduces the rate of occurrence of cardiovascular disorders. Several in vitro
      studies suggest that some components of plant foods, most of which sharing a
      phenolic structure, are endowed with interesting 'pharmacological activities'.
      This article reviews the evidence that links a high dietary intake of
      phytochemicals from various sources with a reduced incidence of coronary heart
      disease.

PMID- 10963716
TI  - Antioxidants and the bioactivity of endothelium-derived nitric oxide.

PMID- 10963717
TI  - Oxidative stress as a signaling mechanism of the vascular response to injury: the
      redox hypothesis of restenosis.
AB  - The prominent role of redox processes in tissue injury and in vascular cell
      signaling suggest their involvement in the repair reaction to vessel injury,
      which is a key determinant of restenosis post-angioplasty. Experimental studies
      showed a protective effect of superoxide dismutase or antioxidants on vasospasm,
      neointimal thickening or remodeling after balloon injury. It was also shown that
      oxidized thiols induce chelatable metal-dependent amplification of the vascular
      repair reaction. Ongoing or completed clinical trials show a promising effect of
      the antioxidant probucol against restenosis. However, few studies addressed the
      molecular physiological mechanisms underlying the redox hypothesis of restenosis.
      We recently showed evidence for marked oxidative stress early after balloon
      injury, with superoxide production mediated primarily by non-endothelial NAD(P)H
      oxidase-type flavoenzyme(s). This effect was closely related to the degree of
      injury. There is evidence supporting a role for such early redox processes in
      apoptotic cell loss and NF-kappa B activation. We present new data on the time
      course of oxidative stress after balloon injury of intact rabbit iliac arteries.
      Our data show that despite substantial neointimal growth and lumen narrowing,
      superoxide production and glutathione levels are unaltered at day 14 and 28 after
      balloon injury. At day 7 after injury, the peak neointimal proliferation in this
      model, there was significant decrease of vascular superoxide dismutase activity,
      without clear evidence of spontaneous superoxide production. Thus, oxidative
      stress after injury is likely to be an early transient event, which parallels the
      inflammatory and proliferative phases of the vascular response. We propose that
      such early redox processes act as dose-dependent signal transducers of gene
      programs that affect the final repair.

PMID- 10963719
TI  - Antioxidants, diabetes and endothelial dysfunction.
AB  - While a damaged endothelium is recognised to be a key accessory to diabetic
      macroangiopathy, awareness is developing that impairments concerning endothelium-
      and nitric oxide (NO)-dependent microvascular function, may contribute to several
      other corollaries of diabetes, such as hypertension, dyslipidaemia and in vivo
      insulin resistance. There are now several reports describing elevations in
      specific oxidant stress markers in both insulin resistance syndrome (IRS) and
      diabetes, together with determinations of reduced total antioxidant defence and
      depletions in individual antioxidants. Such a pro-oxidant environment in diabetes
      may disrupt endothelial function through the inactivation of NO, resulting in the
      attenuation of a fundamental anti-atherogenic and euglycaemic vascular influence.
      Indeed, experimental and clinical data suggest that the supplementation of
      insulin resistant or diabetic states with antioxidants such as vitamin E,
      normalises oxidant stress and improves both endothelium-dependent vasodilation
      and insulin sensitivity. However, the promising potential efficacy of antioxidant
      therapy in cardiovascular disease and diabetes, in either a primary or secondary
      preventative role, awaits definitive clinical demonstration.

PMID- 10963718
TI  - Status of myocardial antioxidants in ischemia-reperfusion injury.
AB  - BACKGROUND: Myocardial ischemia-reperfusion represents a clinically relevant
      problem associated with thrombolysis, angioplasty and coronary bypass surgery.
      Injury of myocardium due to ischemia-reperfusion includes cardiac contractile
      dysfunction, arrhythmias as well as irreversible myocyte damage. These changes
      are considered to be the consequence of imbalance between the formation of
      oxidants and the availability of endogenous antioxidants in the heart.
      OBSERVATIONS: An increase in the formation of reactive oxygen species during
      ischemia-reperfusion and the adverse effects of oxyradicals on myocardium have
      now been well established by both direct and indirect measurements. Although
      several experimental studies as well as clinical trials have demonstrated the
      cardioprotective effects of antioxidants, some studies have failed to
      substantiate the results. Nonetheless, it is becoming evident that some of the
      endogenous antioxidants such as glutathione peroxidase, superoxide dismutase, and
      catalase act as a primary defense mechanism whereas the others including vitamin
      E may play a secondary role for attenuating the ischemia-reperfusion injury. The
      importance of various endogenous antioxidants in suppressing oxidative stress is
      evident from the depression in their activities and the inhibition of cardiac
      alterations which they produce during ischemia-reperfusion injury. The effects of
      an antioxidant thiol containing compound, N-acetylcysteine, and ischemic
      preconditioning were shown to be similar in preventing changes in the ischemic
      reperfused hearts. CONCLUSIONS: The available evidence support the role of
      oxidative stress in ischemia-reperfusion injury and emphasize the importance of
      antioxidant mechanisms in cardioprotection.

PMID- 10963720
TI  - Mechanisms of the pro- and anti-oxidant actions of nitric oxide in
      atherosclerosis.
AB  - The association of nitric oxide (NO) with cardiovascular disease has long been
      recognized and the extensive research on this topic has revealed both pro- and
      anti-atherosclerotic effects. While these contradictory findings were initially
      perplexing recent studies offer molecular mechanisms for the integration of these
      data in the context of our current understanding of the biochemistry of NO. The
      essential findings are that the biochemical properties of NO allow its
      exploitation as both a cell signaling molecule, through its interaction with
      redox centers in heme proteins, and an extremely rapid reaction with other
      biologically relevant free radicals. The direct reaction of NO with free radicals
      can have either pro- or antioxidant effects. In the cell, antioxidant properties
      of NO can be greatly amplified by the activation of signal transduction pathways
      that lead to the increased synthesis of endogenous antioxidants or down regulate
      responses to pro-inflammatory stimuli. These findings will be discussed in the
      context of atherosclerosis.

PMID- 10963721
TI  - Oxidative stress and cardiovascular complications in diabetes: isoprostanes as
      new markers on an old paradigm.
AB  - Long-term vascular complications still represent the main cause of morbidity and
      mortality in diabetic patients. Although randomized long-term clinical studies
      comparing the effects of conventional and intensive therapy have demonstrated a
      clear link between hyperglycemia and the development of complications of
      diabetes, they have not defined the mechanism through which excess glucose
      results in tissue damage. Evidence has accumulated indicating that oxidative
      stress may play a key role in the etiology of diabetic complications.
      Isoprostanes are emerging as a new class of biologically active products of
      arachidonic acid metabolism of potential relevance to human vascular disease.
      Their formation in vivo seems to reflect primarily, if not exclusively, a
      nonenzymatic process of lipid peroxidation. Enhanced urinary excretion of 8-iso
      PGF(2alpha) has been described in association with both type 1 and type 2
      diabetes mellitus, and correlates with impaired glycemic control. Besides
      providing a likely noninvasive index of lipid peroxidation in this setting,
      measurements of specific F(2) isoprostanes in urine may provide a sensitive
      biochemical end point for dose-finding studies of natural and synthetic
      inhibitors of lipid peroxidation. Although the biological effects of 8-iso
      PGF(2alpha) in vitro suggest that it and other isoeicosanoids may modulate the
      functional consequences of lipid peroxidation in diabetes, evidence that this is
      likely in vivo remains inadequate at this time.

PMID- 10963722
TI  - Oxidants, nitric oxide and prostanoids in the developing ocular vasculature: a
      basis for ischemic retinopathy.
AB  - The choroid is the main source of oxygen to the retina. In contrast to the adult,
      the absence of autoregulation of choroidal blood flow in the newborn leads to
      hyperoxygenation of the retina. In the immature retina which contains relatively
      low levels of antioxidants this hyperoxygenation favors peroxidation including
      the generation of biologically active isoprostanes, and results in
      vasoconstriction and vascular cytotoxicity leading to ischemia, which predisposes
      to the development of a vasoproliferative retinopathy, commonly termed
      retinopathy of prematurity. During frequently encountered oxidative stress to the
      perinate, the combined absence of vascular autoregulation and excessive oxygen
      delivery to the eyes of the developing subject is largely the result of a complex
      epigenetic and genetic interplay between prostanoids and nitric oxide (NO)
      systems on vasomotor regulation. The effects of certain prostaglandins are NO
      dependent; conversely, those of NO have also been found to be largely
      prostaglandin I(2)-mediated in the eye; and NO synthase expression seems to be
      significantly regulated by other prostaglandins apparently through activation of
      functional perinuclear prostanoid receptors which affect gene transcription. The
      increased production of both prostaglandins and NO in the perinate augment ocular
      blood flow and as a result oxygen delivery to an immature retina partly devoid of
      antioxidant defenses. The ensuing peroxidation results in impaired circulation
      (partly thromboxane A(2)-dependent) and vascular integrity, leading to ischemia
      which predisposes to abnormal preretinal neovascularization, a major feature of
      ischemic retinopathy. Because tissue oxygenation is largely dependent upon
      circulation and critical in the generation of reactive oxygen species, and since
      the latter exert a major contribution in the pathogenesis of retinopathy of
      prematurity, it is important to understand the mechanisms that govern ocular
      blood flow. In this review we focus on the important and complex interaction
      between prostanoid, NO and peroxidation products on circulatory control of the
      immature retina.

PMID- 10963723
TI  - The antioxidant drug dipyridamole spares the vitamin E and thiols in red blood
      cells after oxidative stress.
AB  - OBJECTIVE: To test the antioxidant effect of therapeutic doses of dipyridamole on
      cellular membranes, human erythrocytes were chosen as an appropriate model to
      study oxidative stress induced by cumene hydroperoxide because of their high
      content in heme-Fe(2+). METHODS: The oxidative stress was induced by incubation
      with 160 micromoll(-1) cumene hydroperoxide and expressed by three main factors:
      lipid peroxidation by means of kinetics of decrease in fluorescence emission of
      the probe incorporated in the cell membranes, vitamin E oxidation and
      intracellular thiol content. The concentrations of dipyridamole tested (2-20
      micromoll(-1)) did not exceed pharmacological doses. RESULTS: After 7 min of
      incubation at 25 degrees C with the oxidant and 20 micromoll(-1) dipyridamole
      thiol content was 50.1%+/-2.6 compared with 31.5%+/-2.4 in the absence of the
      drug. After 12 min vitamin E content was 88.3%+/-2.3 compared with 64.7%+/-3.4 of
      untreated cells in the absence of dipyridamole. Dipyridamole added 5 min after
      the oxidation reaction suppressed the fluorescence decrease for a time
      proportional to the drug concentration. CONCLUSIONS: Thus, at clinically
      realistic doses dipyridamole shows a concentration-dependent antioxidant effect.
      It protects membranes from oxidation and spares the antioxidant power of
      erythrocytes.

PMID- 10963724
TI  - IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear
      factor-kappaB and reduces the inflammatory response in myocardial ischemia
      reperfusion injury.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a ubiquitous rapid response
      transcription factor involved in inflammatory reactions which exerts its effect
      by expressing cytokines, chemokines, and cell adhesion molecules. Oxidative
      stress causes NF-kappaB activation. IRFI 042 is a novel dual vitamin E-like
      antioxidant and we, therefore, investigated its ability to protect the heart from
      oxidative stress and to halt the inflammatory response in a model of myocardial
      ischaemia-reperfusion injury. METHODS: Anaesthetized rats were subjected to total
      occlusion (45 min) of the left main coronary artery followed by 5-h reperfusion
      (MI/R). Sham myocardial ischaemia rats (sham-operated rats) were used as
      controls. Myocardial necrosis, cardiac output, cardiac and plasma vitamin E
      levels, myocardial malondialdehyde (MAL), cardiac SOD activity and elastase
      content (an index of leukocyte infiltration), hydroxyl radical (OH&z.ccirf;)
      formation, cardiac amount of mRNA codifying for ICAM-1 (evaluated by the means of
      reverse transcriptase polymerase chain reaction) and ICAM-1 immunostaining in the
      at-risk myocardium were investigated. NF-kappaB activation and the inhibitory
      protein of NF-kappaB, I-kappaBalpha, were also studied in at-risk myocardium by
      using electrophoretic mobility shift assay (EMSA) and Western blot analysis,
      respectively. RESULTS: The ischaemia-reperfusion model produced wide heart
      necrosis (area at risk-necrotic area=52+/-5%; necrotic area-left ventricle=28+/
      3%), increased cardiac MAL, an index of lipid peroxidation (area at risk=62.5+/
      3.9 nmol/g tissue; necrotic area=80.3+/-5.1 nmol/g tissue), induced tissue
      neutrophil infiltration, and caused a marked decrease in endogenous antioxidants.
      Furthermore, myocardial ischaemia plus reperfusion caused in the area at risk
      peak message for ICAM-1 at 3 h of reperfusion and increased cardiac ICAM-1
      immunostaining at 5 h of reperfusion. NF-kappaB activation was also evident at
      0.5 h of reperfusion and reached its maximum at 2 h of reperfusion. I-kappaBalpha
      was markedly decreased at 45 min of occlusion; peak reduction was observed at 1 h
      of reperfusion and thereafter it was gradually restored. Intraperitoneal
      administration of IRFI 042 (5, 10, 20 mg/kg, 5 min after reperfusion) reduced
      myocardial necrosis expressed as a percentage either of the area at risk (18+/
      4%) or the total left ventricle (11+/-2%), and improved cardiac output. This
      treatment also limited membrane lipid peroxidation in the area at risk
      (MAL=14.3+/-2.5 nmol/g tissue) and in the necrotic area (MAL=26.5+/-3.7 nmol/g
      tissue), restored the endogenous antioxidants vitamin E and superoxide dismutase,
      and inhibited detrimental hydroxyl radical formation. Finally, IRFI 042 blocked
      the activation of NF-kappaB, reduced cardiac ICAM-1 expression, and blunted
      tissue elastase content, an index of leukocytes accumulation at the site of
      injury. CONCLUSIONS: Our data suggest that IRFI 042 is cardioprotective during
      myocardial infarction by limiting reperfusion-induced oxidative stress and by
      halting the inflammatory response.

PMID- 10963725
TI  - The antioxidant effects of a novel iron chelator salicylaldehyde isonicotinoyl
      hydrazone in the prevention of H(2)O(2) injury in adult cardiomyocytes.
AB  - OBJECTIVE: This study was designed to investigate the cardioprotective effect of
      the novel lipophilic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH)
      against the oxidative stress exerted by H(2)O(2) through the production of OH
      radical via the Fenton reaction and to compare them with those of the hydrophilic
      iron chelator deferoxamine (DFO) and the Na(+)/H(+) exchange inhibitor
      methylisobutyl amiloride (MIA). METHODS: We used long-term cultures of
      spontaneously beating adult guinea-pig ventricular cardiomyocytes developed and
      characterized previously in our laboratory. We assessed their contractile
      activity by video-recording as well as the underlying Ca(i)(2+) transients by
      Fura 2 fluorescence. In some experiments we also recorded these functional
      parameters, plus the electrical activity (action potentials) in response to
      electrical stimulation via suction pipettes, in individual freshly isolated
      myocytes. RESULTS: Exposure of the regularly and synchronously beating cultured
      cardiomyocytes to 100 microM H(2)O(2) initially caused a substantial prolongation
      of Ca(i)(2+) transients accompanied by an irregular contractile activity, then in
      contractile arrest and a severalfold increase in cytosolic [Ca(2+)] that
      occurred, within 30 min of H(2)O(2) application. Similar effects were also
      observed using freshly isolated cardiomyocytes. The latter effects were first
      accompanied by significant prolongation of the action potential duration (APD)
      with superimposed early afterdepolarizations followed by a second phase with a
      very fast decrease in APD, contractions, as well as Ca(i)(2+) transients and a
      third phase of inexcitability, contractile arrest, increased cytoplasmic [Ca(2+)]
      and a final contracture. All these effects were irreversible in both types of
      preparations but they could be fully prevented by a 15-min preincubation with 200
      microM SIH. Similar protective effects were observed with DFO, but in this case a
      much higher concentration had to be used (1 mM) and much longer (2 h)
      preincubation was needed. By contrast, 5 microM MIA failed to fully protect the
      cardiomyocytes, although a significant delay (10 min) of the effects of H(2)O(2)
      was observed. CONCLUSIONS: The data indicate that SIH provides a very powerful
      and very fast protection against the oxidative stress exerted by H(2)O(2)
      presumably via the iron-mediated Fenton reaction producing hydroxyl radical (OH),
      whereas the protective effect of DFO is hindred by its very slow and rather
      limited intracellular entry, and the protection that MIA exerts via the
      inhibition of Na(+)/H(+) exchange against H(2)O(2) much less effective.

PMID- 10963726
TI  - Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury.
AB  - OBJECTIVE: Splanchnic artery occlusion shock (SAO) causes an enhanced formation
      of reactive oxygen species (ROS), which contribute to the pathophysiology of
      shock. Here we have investigated the effects of n-acetylcysteine (NAC), a free
      radical scavenger, in rats subjected to SAO shock. METHODS AND RESULTS: Treatment
      of rats with NAC (applied at 20 mg/kg, 5 min prior to reperfusion, followed by an
      infusion of 20 mg/kg/h) attenuated the mean arterial blood and the migration of
      polymorphonuclear cells (PMNs) caused by SAO-shock. NAC also attenuated the ileum
      injury (histology) as well as the increase in the tissue levels of
      myeloperoxidase (MPO) and malondialdehyde (MDA) caused by SAO shock in the ileum.
      There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine
      in the plasma of the SAO-shocked rats after reperfusion. Immunohistochemical
      analysis for nitrotyrosine and for poly(ADP-ribose) synthetase (PARS) revealed a
      positive staining in ileum from SAO-shocked rats. The degree of staining for
      nitrotyrosine and PARS were markedly reduced in tissue sections obtained from SAO
      shocked rats which had received NAC. Reperfused ileum tissue sections from SAO
      shocked rats showed positive staining for P-selectin, which was mainly localised
      in the vascular endothelial cells. Ileum tissue section obtained from SAO-shocked
      rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse
      staining. NAC treatment markedly reduced the intensity and degree of P-selectin
      and ICAM-1 in tissue section from SAO-shocked rats. In addition, in ex vivo
      studies in aortic rings from shocked rats, we found reduced contractions to
      noradrenaline and reduced responsiveness to a relaxant effect to acetylcholine
      (vascular hyporeactivity and endothelial dysfunction, respectively). NAC
      treatment improved contractile responsiveness to noradrenaline, enhanced the
      endothelium-dependent relaxations and significantly improved survival.
      CONCLUSION: Taken together, our results clearly demonstrate that NAC treatment
      exert a protective effect and part of this effect may be due to inhibition of the
      expression of adhesion molecule and peroxynitrite-related pathways and subsequent
      reduction of neutrophil-mediated cellular injury.

PMID- 10963727
TI  - Cardioprotective effect of resveratrol, a natural antioxidant derived from
      grapes.
AB  - BACKGROUND: The major objective of the present study was to examine the
      cardioprotective effect of resveratrol, an antioxidant presents in red wines, in
      the rat after ischemia and ischemia-reperfusion (I-R). METHODS: The left main
      coronary artery was occluded for 30 or 5 min followed by a 30-min reperfusion in
      anesthetized rats. Animals were preinfused with and without resveratrol before
      occlusion and the severity of ischemia- and I-R-induced arrhythmias and mortality
      were compared. RESULTS: Resveratrol pretreatment had no effect on ischemia
      induced arrhythmias nor on mortality. In contrast, a dramatic protective effects
      were observed against I-R-induced arrhythmias and mortality. Resveratrol
      pretreatment both reduced the incidence and duration of ventricular tachycardia
      (VT) and ventricular fibrillation (VF). During the same period, resveratrol
      pretreatment also increased nitric oxide (NO) and decreased lactate dehydrogenase
      levels in the carotid blood. CONCLUSIONS: Resveratrol is a potent antiarrhythmic
      agent with cardioprotective properties in I-R rats. The cardioprotective effects
      of resveratrol in the I-R rats may be correlated with its antioxidant activity
      and upregulation of NO production.

PMID- 10963728
TI  - Reduction of oxidative stress by carvedilol: role in maintenance of ischaemic
      myocardium viability.
AB  - OBJECTIVES: To differentiate the impact of the beta-blocking and the anti-oxidant
      activity of carvedilol in maintaining myocardium viability. METHODS: Isolated
      rabbit hearts, subjected to aerobic perfusion, or low-flow ischaemia followed by
      reperfusion, were treated with two doses of carvedilol, one dose (2.0 microM)
      with marked negative inotropic effect due to beta-blockage and the other (0.1
      microM) with no beta-blockage nor negative inotropism. Carvedilol was compared
      with two doses of propranolol, 1.0 - without - and 5.0 microM - with negative
      inotropic effect. Anti-oxidant activity was measured as the capacity to
      counteract the occurrence of oxidative stress and myocardium viability as
      recovery of left ventricular function on reperfusion, membrane damage and
      energetic status. RESULTS: Carvedilol counteracted the ischemia and reperfusion
      induced oxidative stress: myocardial content of reduced glutathione, protein and
      non-protein sulfhydryl groups after ischaemia and particularly after reperfusion,
      was higher in hearts treated with carvedilol, while the myocardial content of
      oxidised glutathione was significantly reduced (0.30+/-0.03 and 0.21+/-0.02 vs.
      0.39+/-0.03 nmol/mg prot, both P<0.01, in 0.1 and 2.0 microM). At the same time,
      carvedilol improved myocardium viability independently from its beta-blocking
      effect. On the contrary, propranolol maintained viability only at the higher
      dose, although to a lesser extent than carvedilol. This suggests that the effects
      of propranolol are dependent on energy saving due to negative inotropism. The
      extra-protection observed with carvedilol at both doses is likely due to its anti
      oxidant effect. CONCLUSIONS: Our data show that the anti-oxidant activity of
      carvedilol is relevant for the maintenance of myocardium viability.

PMID- 10963729
TI  - Effect of vitamin E supplementation on antibody levels against malondialdehyde
      modified LDL in hyperlipidemic hamsters.
AB  - OBJECTIVE: The aim of this work was to investigate the effect of vitamin E (VE)
      supplementation on the formation of autoantibodies against oxidized low density
      lipoproteins (LDL) in a hyperlipidemic animal model. METHODS: Thirty-four male
      hamsters (Mesocricetus auratus), (4 weeks old) were divided into three groups:
      Group A (n=9) was fed with standard rodent chow; group B (n=13) was fed with a
      standard rodent chow plus 2% cholesterol and 10% butter and group C (n=12) was
      fed with the same diet plus 0.2% (w/w) VE. Blood samples were collected by
      intracardiac puncture and antibody levels were determined in each animal at 4
      weeks of age and after 20 weeks of experimental diet. A modified ELISA technique
      was used to analyze the modulation of autoantibody titers against an epitope of
      oxidized LDL in serum samples. Antigens prepared for the ELISA tests were
      characterized using spectrofluorimetry. Serum VE levels were determined in the
      lipidic fractions by HPLC. RESULTS: The groups fed with cholesterol-fat enriched
      diet presented a three-fold increase in total serum cholesterol and two-fold
      increase in serum triglycerides compared to the control group. VE supplementation
      played no role in serum cholesterol and serum triglyceride concentrations but led
      to a decreased autoantibody (anti-LDL-malondialdehyde) formation (P<0.05).
      CONCLUSIONS: Our results show that VE supplementation leads to a lower production
      of autoantibodies against oxidized LDL, suggesting a protective effect of VE
      against in vivo oxidation of LDL particles, in a dose-dependent manner.

PMID- 10963730
TI  - Evidence for P(2)-purinoceptors contribution in H(2)O(2)-induced contraction of
      rat aorta in the absence of endothelium.
AB  - OBJECTIVE: H(2)O(2) can contract many arteries, however the underlying mechanisms
      are not fully understood. This study aims to test whether H(2)O(2)-induced
      vasoconstriction could be functionally attributed to the activation of P(2)
      purinoceptors in rat aorta and to explore its possible signaling mechanisms.
      METHODS: Isometric tension recording of H(2)O(2) and ATP-induced contractions of
      rat aortic rings were compared in the absence or presence of various
      pharmacological tools to identify their possible common signaling pathways.
      RESULTS: Both H(2)O(2) and ATP induced transient phasic contractions in a
      concentration-dependent manner (1-1000 microM). Removal of endothelium
      potentiated the contractile responses to H(2)O(2) and to ATP. H(2)O(2) (30
      microM)-induced phasic contraction could be abolished by catalase (800 U/ml), but
      not affected by SOD (150 U/ml), DMSO (5 mM) and apyrase (5 U/ml), suggesting no
      involvement of O(2)(-), hydroxyl free radicals and ATP release. Also, several
      receptor antagonists including phentolamine, atropine, methysergide and
      chlorpheniramine (each 3 microM) were without effect on H(2)O(2) (30 microM)
      induced phasic contraction, suggesting no involvement of typical neurotransmitter
      release. However, both H(2)O(2) (30 microM) and ATP (1 mM)-induced phasic
      contractions not only presented homologous desensitization, but also showed
      heterogeneous desensitization. Furthermore, the phasic contractions in response
      to H(2)O(2) (30 microM) or ATP (100 microM) could be inhibited or abolished in a
      concentration dependent manner by RB-2 and suramin (10-100 microM), two widely
      used P(2)-purinoceptor antagonists, with only partial inhibition by Evans blue
      (300 microM), a moderately selective P(2x) receptor blocker, or by alpha-beta
      methylene-ATP (100 microM), a selective P(2x) receptor desensitizer. On the other
      hand, both H(2)O(2) (30 microM) and ATP (100 microM)-induced phasic contractions
      were also attenuated, to different degree, by inhibitors of several enzymes
      including PLC, PKC, PLA(2) and cyclooxygenase. Lastly, removal of extracellular
      Ca(2+) or pretreatment with procaine (10 mM) and dantrolene (30 microM), two
      putative intracellular Ca(2+) release blockers, or with Ni(2+) (100 microM) and
      tetrandrine (5 microM), two Ca(2+) channel blockers, all significantly inhibited
      H(2)O(2) and ATP-induced contractions. However, nifedipine (1 microM), a voltage
      dependent L-type Ca(2+) channel blocker, was without effect. CONCLUSIONS: Our
      results demonstrate that H(2)O(2)-induced phasic contraction of rat aorta
      involves, at least in part, the activation of P(2)-purinoceptors in the aortic
      smooth muscle cells

PMID- 10963731
TI  - New insights on myocardial pyridine nucleotides and thiol redox state in ischemia
      and reperfusion damage.
AB  - OBJECTIVE: to investigate the changes of pyridine nucleotides and thiol redox
      state in cardiac tissue following ischemia and reperfusion. NADH/NAD and
      NADPH/NADP redox couples were specifically studied and the influence of NADPH
      availability on cellular thiol redox was also investigated. METHODS: isolated
      rabbit hearts were Langendorff perfused and subjected to a protocol of ischemia
      and reperfusion. An improved technique for extraction and selective quantitation
      of pyridine nucleotides was applied. RESULTS: ischemia and reperfusion induced an
      increase in diastolic pressure, limited recovery in developed pressure and loss
      of creatine phosphokinase. Creatine phosphate and ATP were decreased by ischemia
      and only partially recovered during reperfusion. NADH was increased (from 0. 36+/
      0.04 to 1.96+/-0.15 micromol/g dry wt. in ischemia, P<0.001), whereas NADPH
      decreased during ischemia (from 0.78+/-0.04 to 0. 50+/-0.06 micromol/g dry wt.,
      P<0.01) and reperfusion (0.45+/-0.03 micromol/g dry wt.). Furthermore, we
      observed: (a) release of reduced (GSH) and oxidised glutathione (GSSG) during
      reperfusion; (b) decreased content of reduced sulfhydryl groups during ischemia
      and reperfusion (GSH: from 10.02+/-0.76 to 7.11+/-0.81 nmol/mg protein, P<0.05,
      and to 5.48+/-0.57 nmol/mg protein; protein-SH: from 280.42+/-12.16 to 135.11+/
      17.00 nmol/mg protein, P<0.001, and to 190.21+/-11.98 nmol/mg protein); (c)
      increased content in GSSG during reperfusion (from 0.17+/-0.02 to 0.36+/-0.02
      nmol/mg protein, P<0.001); (d) increased content in mixed disulphides during
      ischemia (from 6.14+/-0.13 to 8.31+/-0.44 nmol/mg protein, P<0.01) and
      reperfusion (to 9.87+/-0.82 nmol/mg protein, P<0.01). CONCLUSIONS: under severe
      low-flow ischemia, myocardial NADPH levels can decrease despite the accumulation
      of NADH. The reduced myocardial capacity to maintain NADPH/NADP redox potential
      can result in thiol redox state changes. These abnormalities may have important
      consequences on cellular function and viability.

PMID- 10963732
TI  - Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes.
AB  - Previous studies have demonstrated that vascular responses to acetylcholine (ACh)
      are impaired in diabetes mellitus (DM). OBJECTIVE: Since reactive oxygen species
      (ROS) generation is increased in various disease states including DM, and a
      direct reaction between nitric oxide (NO) and superoxide anion has been
      demonstrated, we tested the hypothesis that inhibition of ROS will restore
      coronary microvascular responses to ACh in a dog model of DM (alloxan 60 mg/kg,
      i.v., 1 week prior to study). METHODS: Changes in coronary microvascular
      diameters in diabetic (blood glucose >200 mg%) and normal animals to ACh (1-100
      microM, topically) in the presence and absence of superoxide dismutase and
      catalase were measured using intravital microscopy coupled to stroboscopic epi
      illumination and jet ventilation. RESULTS: In diabetic animals in the absence of
      ROS scavengers, ACh induced coronary microvascular dilation was impaired when
      compared to normal animals (ACh 100 microM: DM=25+/-5%; normal=64+/-13%, P<0.05).
      Topical application of SOD (250 U/ml) and catalase (250 U/ml) restored to normal
      ACh induced coronary microvascular responses in DM while having no affect in
      normal animals. Responses to adenosine and nitroprusside were not different
      between normal and diabetic groups. CONCLUSIONS: These data provide direct
      evidence that oxygen-derived free radicals contribute to impaired endothelium
      dependent coronary arteriolar dilation in diabetic dogs in vivo.

PMID- 10963733
TI  - Inhibition of purified soluble guanylyl cyclase by L-ascorbic acid.
AB  - OBJECTIVE: L-Ascorbic acid has been described to exert multiple beneficial
      effects in cardiovascular disorders associated with impaired nitric oxide
      (NO)/cGMP signalling. The aim of the present study was to investigate the effect
      of vitamin C on the most prominent physiological target of endogenous and
      exogenous NO, i.e. soluble guanylyl cyclase (sGC). METHODS: To address this issue
      we used a highly purified enzyme preparation from bovine lung (from the
      slaughterhouse). Enzymic activity was measured by a standard assay based on the
      conversion of [alpha-32P]GTP to [32P]cGMP and the subsequent quantification of
      the radiolabelled product. NO was quantified using a commercially available Clark
      type electrode. RESULTS: Stimulation of sGC by the NO donor 2, 2-diethyl-1
      nitroso-oxyhydrazine was inhibited by ascorbate with an IC(50) of approximately 2
      microM. Maximal enzyme inhibition ( approximately 70%) was observed at 0.1-1 mM
      vitamin C. Stimulation of sGC by the NO-independent activator protoporphyrin-IX
      was also inhibited with similar potency. The effect of ascorbate on sGC was
      largely antagonised by reduced glutathione (1 mM) and the specific iron chelator
      diethylenetriaminepentaacetic acid (0.1 mM). Electrochemical experiments revealed
      that NO is potently scavenged by vitamin C. Consumption of NO by ascorbate was
      prevented by reduced glutathione (1 mM), diethylenetriaminepentaacetic acid (0.1
      mM) and superoxide dismutase (500 units/ml) whereas up to 5000 units/ml
      superoxide dismutase failed to restore sGC activity. CONCLUSIONS: Our results
      suggest that physiological concentrations of L-ascorbic acid diminish cGMP
      accumulation via both scavenging of NO and direct inhibition of sGC.

PMID- 10963734
TI  - Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide
      dismutase restores nitric oxide availability in the SHRSP.
AB  - OBJECTIVE: Previous studies from our group have shown a deficit in nitric oxide
      (NO) bioavailability and an excess production of the superoxide anion (O(2)(-))
      in the stroke prone spontaneously hypertensive rat (SHRSP) compared to the
      normotensive Wistar Kyoto (WKY) strain. This present study has investigated
      whether adenoviral-mediated gene transfer of human eNOS or Cu/ZnSOD can alter the
      NO/O(2)(-) balance, thereby improving endothelial function. METHODS: A
      recombinant adenovirus, Ad/Hu/eNOS, containing the human eNOS cDNA fragment was
      generated by homologous recombination in 293 cells. Ad/Hu/eNOS or Ad/Cu/ZnSOD was
      delivered into SHRSP carotid arteries in vivo, using a titre of 2x10(9)-2x10(10)
      plaque forming units (pfu)/ml, and the effect on gene expression was observed 24
      h later. RESULTS: Western blotting confirmed increased enzyme levels of eNOS and
      Cu/ZnSOD in the viral-infused vessels. Ex vivo, the pressor response to
      phenylephrine (PE) in the presence of L-NAME was increased in the eNOS-infused
      arteries relative to the contralateral controls, indicating restoration of basal
      NO availability to that observed in untreated control WKY rats. Infusion of the
      SOD virus produced a statistically insignificant increase in NO bioavailability.
      CONCLUSIONS: Our results support our previous findings obtained using a bovine
      eNOS recombinant adenovirus, that recombinant adenoviral gene transfer of human
      eNOS has a significant effect on NO bioavailability. In contrast, AdCu/ZnSOD gene
      transfer does not elicit an effect in our model. These results indicate that
      short-term overexpression of a recombinant eNOS, but not Cu/ZnSOD gene, in
      carotid arteries of the SHRSP is an effective means of locally increasing NO
      bioavailability to improve endothelial function.

PMID- 10963735
TI  - Alteration in plasma antioxidant capacities in chronic renal failure and
      hemodialysis patients: a possible explanation for the increased cardiovascular
      risk in these patients.
AB  - OBJECTIVE: The high incidence of cardiovascular diseases in chronic renal failure
      (CRF) and hemodialyzed (HD) patients is now well established and the involvement
      of oxidative stress has been hypothesized in these phenomena. The aim of our
      study was to evaluate the level of oxidative stress in healthy controls (CTL)
      compared with CRF and HD patients before (pre-HD) and after (post-HD) the
      dialysis session, carried out on a high biocompatible polyacrylonitrile membrane
      AN69. METHODS: Several indicators of the extracellular redox status were
      evaluated in plasma. The ascorbyl free radical (AFR) was directly measured using
      electron spin resonance spectroscopy (ESR) and expressed with respect to the
      vitamin C level to obtain a direct index of oxidative stress. Indirect plasma
      parameters such as vitamin E, thiol and uric acid levels were also quantified.
      The plasma antioxidant status (PAS) was evaluated by the allophycocyanin test.
      Nitric oxide (NO) stable-end metabolites: nitrites and nitrates (NO(x)), were
      measured in plasma. RESULTS: In CRF patients, vitamin C and thiol levels were
      low, and the AFR/vitamin C ratio high compared with the CTL. On the other hand,
      PAS and uric acid levels were shown to be higher in CRF patients. After the
      dialysis session, vitamin C level decreased and AFR/vitamin C ratio increased.
      The thiol levels were shown to be increased, in return PAS and uric acid levels
      were significantly lower after the dialysis session. NO(x) levels rose during
      CRF, but were significantly decreased after the dialysis procedure. No
      differences in vitamin E status were observed between CTL, CRF and HD patients.
      CONCLUSION: Our study demonstrates that profound disturbances in the
      extracellular redox system occur during the course of chronic renal failure and
      hemodialysis, and may provide an explanation for the cardiovascular complications
      in these patients.

PMID- 10963736
TI  - Aging is associated with increased lipid peroxidation in human hearts, but not
      with mitochondrial respiratory chain enzyme defects.
AB  - BACKGROUND: Aging is associated with increased oxidative damage at multiple
      cellular and tissular levels. A decrease in mitochondrial function has repeatedly
      been advocated as a primary key event, especially on the basis of analysis of
      skeletal muscle mitochondria. However, some doubts on this issue have arisen when
      confounding variables (such as physical activity or smoking habit) have been
      taken into account in the analysis of mitochondrial respiratory chain (MRC)
      enzyme activities or when additional analytical parameters such as enzyme ratios
      have been considered. OBJECTIVE: To determine whether oxidative damage and enzyme
      activities of the MRC are influenced by the aging process in human hearts.
      PATIENTS AND METHODS: We studied cardiac muscle obtained from 59 organ donors
      (age: 56+/-12 years, 75% men). Oxidative membrane damage was evaluated through
      the assessment of lipid peroxidation. Absolute and relative enzyme activities
      (AEA and REA, respectively) of complex I, II, III and IV of the MRC were
      spectrophotometrically measured. Stoichiometric relationships among MRC complexes
      were also assessed through calculating MRC ratios. Linear regression analyses
      were employed to disclose any potential correlation between mitochondrial
      dysfunction and aging. RESULTS: We found a progressive, significant increase of
      heart membrane lipid peroxidation with aging (P<0.05). Conversely, neither AEA
      nor REA decreased with age (P=n.s. for all complexes). Similarly to observations
      in other tissues, we found that stoichiometry of the MRC enzymes is maintained
      within a narrow range in human hearts. When the effects of aging on MRC ratios
      were explored, we failed again in demonstrating any subtle disarray. CONCLUSION:
      MRC enzymes remain preserved in heart with aging, and thus they cannot be
      considered the main cause of the increased oxidative damage associated with
      aging.

PMID- 10963737
TI  - Coincident activation of mGluRs and mAChRs imposes theta frequency patterning on
      synchronised network activity in the hippocampal CA3 region.
AB  - Activation of metabotropic glutamate receptors (mGluRs) with the broad spectrum
      mGluR agonist 1S,3R ACPD (10-50 microM) induced spontaneous field potentials at
      low frequencies ('burst-mode' activity; <1 Hz) in the CA3 region of rat
      hippocampal slices. At higher concentrations (100-400 microM) ACPD switched this
      form of activity to a second, more complex pattern of activity in which
      intermittent episodes of theta frequency oscillations predominated ('theta-mode'
      activity; 4-14 Hz). Both patterns of activity were evoked by selective activation
      of group I mGluRs and, in particular, could be induced by activation of mGluR5
      alone using the subtype selective agonist CHPG (0.5-5 mM). In contrast,
      activation of group II mGluRs (DCG IV; 100 microM) produced only burst-mode
      behaviour whilst activation of group III mGluRs (L-AP4; 100 microM) did not
      result in synchronised network activity. Concurrent extra- and intracellular
      recordings demonstrated that this mGluR-induced theta-mode activity represented
      the synchronous firing of CA3 pyramidal cells and that it shared a similar
      temporal signature to that generated by activation of muscarinic acetylcholine
      receptors (mAChRs). Furthermore, application of mGluR and mAChR agonists at
      concentrations sufficient to produce only burst-mode activity when applied
      individually, produced theta-mode activity when co-applied. These data suggest
      that the level of activation of different mGluRs and mAChRs crucially determine
      the pattern of rhythmical network activity generated in the hippocampal CA3
      network. These results also indicate that individual receptor subtypes (i.e.
      mGluR5) can initiate patterns of coherent network activity but that interactions
      between the cholinergic and glutamatergic transmitter systems may also be
      important factors in governing the temporal patterning of hippocampal network
      activity.

PMID- 10963738
TI  - Fear conditioning-induced time- and subregion-specific increase in expression of
      mGlu5 receptor protein in rat hippocampus.
AB  - Memory formation involves encoding, consolidation and retention. These processes
      have been the subjects of considerable research, but physiological mechanisms
      underlying consolidation have proved difficult to dissociate experimentally.
      Previous reports have indicated a role for metabotropic glutamate receptors
      (mGluRs) in memory formation, and we here examined the specific role of mGluRs in
      the consolidation phase of memory formation. Particular weight was given to the
      hippocampus due to a high expression level for group I mGluRs and its outstanding
      role in spatial learning. Rats were first trained in a combined context and cue
      conditioning paradigm. Then, ex vivo analysis of neuronal tissue taken from
      hippocampal CA1, CA3 or dentate gyrus of behaviourally trained animals showed a 3
      fold hyper-expression of mGluR5 protein in CA3 one day after acquisition
      training. This increase was transient and greatly diminished within ten days. The
      decline was paralleled by an increase in mGluR5 protein expression in CA1 and, to
      a lesser extent, in dentate gyrus, ten days posttraining. Overexpression in CA1
      was also obtained after 9 days of extinction training. These data provide new
      insight into the role of the hippocampus and its subregions in memory
      consolidation. They support the notion that mGluRs in CA3 may play a part in
      short-term, and those in CA1 may play a part in long-term consolidation of
      memory.

PMID- 10963739
TI  - Group III metabotropic glutamate receptors modulate long-term depression in the
      hippocampal CA1 region of two rat strains in vivo.
AB  - Hippocampal long-term depression (LTD) involves a long-lasting decrease in
      synaptic transmission which is induced by low-frequency stimulation (LFS).
      Evidence exists that variability in the responsiveness of rat strains to LFS
      occurs. Thus, Wistar rats readily express LTD in vivo, whereas Hooded Lister rats
      demonstrate at best short-term depression (STD) in response to LFS. Group III
      metabotropic glutamate receptor (mGluR)-involvement in the induction of LTD in
      freely moving rats has not yet been investigated. This study therefore examined
      the effect of group III mGluR activation and inhibition on LTD expression, and
      evaluated these effects in Wistar and Hooded Lister rats. Animals were
      chronically implanted with recording and bipolar stimulating electrodes in the
      CA1 region, and an injection cannula in the lateral cerebral ventricle. LFS (1
      Hz, 900 pulses) induced LTD in Wistar, and STD in Hooded Lister rats. Agonist
      priming with L-2-amino-4-phosphonobutanoic acid (AP4, 400 nmol/5 microl)
      facilitated LTD expression in Hooded Lister but not Wistar rats. The antagonist
      (RS)-alpha-cyclopropyl-4-phosphonophenylglycine inhibited the facilitatory
      effects of AP4 in Hooded Lister- and impaired LTD expression in Wistar rats.
      These data imply a role for group III mGluRs in hippocampal LTD in vivo, and
      suggest that differences in this mGluR system may account, in part, for strain
      dependent variations in LTD expression.

PMID- 10963740
TI  - The selective AMPA receptor antagonist GYKI 53784 blocks action potential
      generation and excitotoxicity in the guinea pig cochlea.
AB  - The role of AMPA receptors in cochlear synaptic transmission and excitotoxicity
      was investigated by comparing the actions of a selective AMPA antagonist GYKI
      53784 (LY303070) with additional AMPA/kainate antagonists, GYKI 52466 and DNQX,
      and the NMDA antagonist, D-AP5, in several electrophysiological,
      neurotoxicological and histochemical tests. GYKI 53784 had the same potency as
      DNQX and was 10 times more potent than GYKI 52466 in reducing auditory nerve
      activity. The NMDA antagonist D-AP5 had no effect on auditory nerve activity.
      When single-fiber activity was blocked with GYKI 53784, the effects of AMPA or
      kainate were also antagonized. GYKI 53784 completely blocked excitotoxicity (i.e.
      destruction of the afferent nerve endings) induced by AMPA and kainate. The
      histochemical detection of Co(2+) uptake was used to study Ca(2+) influx within
      the primary auditory nerve cells. Application of AMPA induced no significant
      Co(2+) uptake into the cells, suggesting that these receptors normally have a
      very low permeability to Ca(2+). Application of kainate induced significant
      Co(2+) uptake that was blocked by the AMPA receptor antagonist GYKI 53784
      suggesting that kainate stimulated Ca(2+) entry through AMPA receptor channels.
      Results suggest that AMPA-preferring receptors are functionally located at the
      sensory cell-afferent synapse whereas NMDA and kainate receptors are not.

PMID- 10963741
TI  - Amplification of cortical serotonin release: a further neurochemical action of
      the vigilance-promoting drug modafinil.
AB  - The present in vitro and in vivo studies examined the effects of modafinil on
      serotonergic transmission in the rat frontal cortex. In the in vitro study
      modafinil (0.3-30 microM) increased electrically-evoked, but not spontaneous,
      serotonin ([(3)H]5-HT) efflux from cortical slices in a concentration-dependent
      manner while the indirect serotonin agonist dl-fenfluramine (1-15 microM)
      enhanced both spontaneous and evoked [(3)H]5-HT efflux. The effects of modafinil
      were more pronounced when the 5-HT reuptake was blocked by paroxetine. Contrary
      to paroxetine (0.3-3 microM) and dl-fenfluramine (1-5 microM), modafinil failed
      to influence the [(3)H]5-HT uptake. In the in vivo study modafinil (3-100 mg/kg
      i.p.) increased 5-HT dialysate levels, the maximal effect being already reached
      at the 30 mg/kg dose. dl-fenfluramine (5 mg/kg) induced an increase in 5-HT
      levels which was significantly higher than that displayed by modafinil at 30
      mg/kg. In the presence of paroxetine (3 microM), the effect of modafinil at 30
      mg/kg was higher than that observed in the absence of 5-HT reuptake inhibition.
      Finally, in the presence of the selective 5-HT(1A) receptor agonist 8-OH-DPAT,
      modafinil at 100 mg/kg failed to affect 5-HT dialysate levels. These results
      demonstrate that modafinil regulates cortical serotonergic transmission and
      suggest that the drug preferentially acts by amplifying the electro
      neurosecretory coupling mechanisms and via mechanisms which do not involve the
      reuptake process.

PMID- 10963742
TI  - Endogenous serotonin enhances the release of dopamine in the striatum only when
      nigro-striatal dopaminergic transmission is activated.
AB  - In this study, we use in vivo microdialysis to investigate the influence of
      endogenous serotonin (5-HT) on striatal dopamine (DA) and 5-hydroxyidoleacetic
      acid (5-HIAA) efflux in both basal and activated conditions. The selective
      serotonin reuptake inhibitors citalopram and fluoxetine were used to mobilize
      endogenous 5-HT. In halothane-anaesthetized rats, citalopram (5 mg/kg, i.p.),
      administered either alone or in combination with the 5-HT(1A) receptor antagonist
      WAY 100635 (0.1 mg/kg, s.c.), while reducing striatal 5-HIAA outflow (-25 and 
      15%, respectively), had no effect on basal DA output. When locally applied into
      the striatum, citalopram had no effect at 1 microM concentration, but enhanced DA
      release after its perfusion at 25 and 100 mircroM concentrations (+27% and +67%,
      respectively). However, the injection of the neurotoxin 5,7-dihydroxytryptamine
      into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum,
      failed to modify the effect of 25 microM citalopram. In freely-moving rats, the
      intrastriatal infusion of citalopram or fluoxetine (1 microM each), had no effect
      on its own, but significantly enhanced the increase in DA outflow induced by the
      subcutaneous administration of 0.01 mg/kg haloperidol (+31% and +30% for
      citalopram and fluoxetine, respectively). These findings indicate that, in the
      striatum, endogenous 5-HT has no influence on DA release under basal conditions,
      but positively modulates DA outflow when nigro-striatal DA transmission is
      activated.

PMID- 10963745
TI  - Differential modulation of the 5-HT(4) receptor agonists and antagonist on rat
      learning and memory.
AB  - Recent data suggest that activation of 5-HT(4) receptors may modulate cognitive
      processes such as learning and memory. In the present study, the effects of two
      potent and selective 5-HT(4) agonists, RS 17017 [1-(4-amino-5-chloro-2
      methoxyphenyl)-5- (piperidin-1-yl)-1-pentanone hydrochloride] and RS 67333 [1(4
      amino-5-chloro-2-methoxyphenyl)-3- (1-n-butyl-4-piperidinyl)-1-propanone], were
      studied in an olfactory associative discrimination task. The implication of 5
      HT(4) receptors in the associative discriminative task was suggested by the
      following observation. Injection of a selective 5-HT(4) receptor antagonist RS
      67532 [1-(4-amino-5-chloro-2-(3, 5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1
      pentanone; 1 mg/kg: i.p.] before the third training session induced a consistent
      deficit in associative memory during the following training sessions. This
      deficit was absent when the antagonist was injected together with either a
      specific hydrophilic 5-HT(4) (RS 17017, 1 mg/kg) or a specific hydrophobic (RS
      67333, 1 mg/kg) 5-HT(4) receptor agonist. RS 67333 was more potent than RS 17017.
      This difference in potency certainly reflects a difference in their capacity to
      enter into the brain. This is also likely to be the reason why, injected alone,
      the hydrophobic 5-HT(4) agonist (RS 67333) but not the hydrophilic 5-HT(4)
      agonist (RS 17017) improved learning and memory performance.

PMID- 10963744
TI  - In vivo modulation of nucleus tractus solitarius (NTS) neurones by activation of
      5-hydroxytryptamine(2) receptors in rats.
AB  - In in vivo experiments, 5-hydroxytryptamine (5-HT) and (+/-)-2,5-dimethoxy-4
      iodoamphetamine HCl (DOI), a 5-HT(2) receptor agonist, were applied by
      ionophoresis to rat nucleus tractus solitarius (NTS) neurones identified by their
      vagal and cardiopulmonary afferent inputs to test whether the response of NTS
      cells to 5-HT(2) receptor activation was related to whether they received mono-
      or polysynaptic vagal inputs and their presumed function as defined by their
      afferent input. Cells were classified on the basis of the variability of the
      latency of the vagal-evoked spikes: this varied by less than 3 ms for Group 1,
      from 3 to 5 ms for Group 2, and more than 5 ms for Group 3. Both 5-HT and DOI
      inhibited most Group 1 cells (16/18) and inactive (without ongoing activity)
      cells (8/13) in Group 2. Cells inhibited by DOI were also inhibited by
      cardiopulmonary afferent stimulation, evoked by atrial phenylbiguanide
      administration. By contrast, application of 5-HT and DOI excited the majority of
      Group 3 cells (14/19) and Group 2 with ongoing activity (7/9). Cells excited by
      DOI were also activated by cardiopulmonary stimulation. Both actions of DOI were
      reversed by application of ketanserin (n=15). In conclusion, these data
      demonstrate that activation of 5-HT(2) receptors in the NTS produces different
      effects dependent on whether the neurones received mono- or polysynaptic vagal
      input and their response to cardiopulmonary afferent stimulation.

PMID- 10963743
TI  - Regulation of 5-HT(2A) receptor mRNA levels and binding sites in rat frontal
      cortex by the agonist DOI and the antagonist mianserin.
AB  - In the present study we have characterized the time course of effect of
      administration of the serotonin(2) (5-HT(2)) receptor antagonist mianserin, or
      the 5-HT(2) receptor agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane
      (DOI), on 5-HT(2A) receptor binding sites and mRNA levels in rat frontal cortex.
      Radioligand binding and ribonuclease protection assays were performed with
      separate hemispheres of frontal cortex from each animal to examine concomitant
      changes in 5-HT(2A) receptor sites and mRNA levels. The decrease in cortical 5
      HT(2A) receptor sites in response to chronic DOI administration was not
      accompanied by changes in 5-HT(2A) receptor mRNA. A single injection of DOI
      produced a transient decrease in 5-HT(2A) receptor mRNA levels detected 1 h post
      injection. The density of 5-HT(2A) receptor sites, however, was not significantly
      reduced following a single injection of DOI. The down-regulation of cortical 5
      HT(2A) receptor sites in response to a single injection of mianserin was
      accompanied by reductions in 5-HT(2A) receptor mRNA levels. Following 4 days of
      mianserin administration, however, we did not observe a change in 5-HT(2A)
      receptor mRNA levels, although 5-HT(2A) receptor density was decreased. Thus,
      changes in receptor mRNA may initially contribute to the down-regulation of 5
      HT(2A) receptors in response to acute mianserin administration. Sustained changes
      in 5-HT(2A) receptor mRNA, however, appear not to be involved in maintaining the
      down-regulation of 5-HT(2A) receptor number with chronic mianserin
      administration. Mechanisms other than the regulation of receptor mRNA levels
      appear to underlie the down-regulation of 5-HT(2A) receptor sites in response to
      chronic administration of the agonist DOI.

PMID- 10963746
TI  - Sibutramine does not decrease the number of 5-HT re-uptake sites in rat brain
      and, like fluoxetine, protects against the deficits produced by dexfenfluramine.
AB  - The effect of sibutramine and dexfenfluramine on 5-HT re-uptake sites, labelled
      with [(3)H]paroxetine, have been determined in various rat brain regions. In
      addition, the ability of fluoxetine and sibutramine to protect against the
      changes in [(3)H]paroxetine binding produced by dexfenfluramine was examined.
      Sibutramine (9 mg/kg, p.o.) and dexfenfluramine (1, 3 and 10 mg/kg, p.o.) were
      administered twice daily (before 09.00 h and after 16.00 h) for four days,
      followed by a 14 day drug-free period. In the protection studies, fluoxetine (10
      mg/kg, i.p.) and sibutramine (9 mg/kg, p.o.) were given 1 h prior to
      dexfenfluramine (10 mg/kg, p.o.) using the same dosing regimen as described
      above. Sibutramine (9 mg/kg, p.o.; three times its ED(50) to inhibit food intake
      at 2 h) had no significant effect on the number or affinity of 5-HT re-uptake
      sites the brain regions studied. In contrast, dexfenfluramine at an equivalent
      dose (3 mg/kg, p.o.) significantly decreased the number of 5-HT re-uptake sites
      in frontal cortex (by 35%), hippocampus (by 47%) and hypothalamus (by 27%). This
      effect was dose-dependent with marked decreases (by 58-84%) in the number of
      sites following 10 mg/kg, p.o. These effects were not associated with changes in
      binding affinity. Fluoxetine (10 mg/kg, i.p.) completely blocked the effect of
      dexfenfluramine (10 mg/kg, p.o.) without having any significant effect alone.
      Sibutramine (9 mg/kg, p.o.) also blocked the effects of dexfenfluramine, although
      the reversal was only partial in frontal cortex, hippocampus and hypothalamus.
      Thus sibutramine, unlike dexfenfluramine, does not alter brain 5-HT re-uptake
      sites. Furthermore, sibutramine and fluoxetine protect against the deficits in 5
      HT re-uptake sites produced by dexfenfluramine. These data provide further
      evidence that sibutramine is a 5-HT re-uptake inhibitor and it does not have
      neurotoxic potential.

PMID- 10963747
TI  - Inhibition of 5-hydroxytryptamine reuptake by the antidepressant citalopram in
      the locus coeruleus modulates the rat brain noradrenergic transmission in vivo.
AB  - The in vivo effect of the serotonin (5-HT) reuptake inhibitor antidepressant
      citalopram, administered in the locus coeruleus (LC), on noradrenergic
      transmission was evaluated in the rat brain. In dual-probe microdialysis assays,
      citalopram (0.1-100 microM), in a concentration-dependent manner, increased
      extracellular noradrenaline (NA) in the LC and simultaneously decreased
      extracellular NA in the cingulate cortex (Cg). These effects of citalopram were
      abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine
      (400 mg/kg, i.p.). When the alpha(2)-adrenoceptor antagonist RS79948 (1 microM)
      was perfused in the LC, local citalopram increased NA dialysate in the LC but no
      longer modified NA dialysate in the Cg. In electrophysiological experiments, the
      administration of citalopram (100 microM) in the LC by reversal dialysis,
      decreased the firing rate of LC neurones. The results demonstrate in vivo that
      local administration of citalopram in the LC leads to a decreased release of NA
      in the Cg. This modulation seems to be the result of an increase in NA
      concentration in the LC and the subsequent inhibition of LC neurones via alpha(2)
      adrenoceptors. The effects of citalopram are dependent on the presence of
      endogenous 5-HT in the LC.

PMID- 10963748
TI  - The suramin analogue NF279 is a novel and potent antagonist selective for the
      P2X(1) receptor.
AB  - The suramin analogue 8,8'-(carbonylbis(imino-4, 1-phenylenecarbonylimino-4,1
      phenylenecarbonylimino)) bis(1,3,5-naphthalenetrisul fonic acid) (NF279) was
      analysed with respect to its potency and P2X receptor subtype selectivity. Two
      electrode voltage-clamp measurements were performed with Xenopus laevis oocytes
      expressing homomultimeric rat P2X(1), P2X(2), P2X(3) and human P2X(4) receptors.
      For the fast desensitising P2X(1) and P2X(3) receptors, IC(50) values strongly
      depended on whether oocytes were pre-incubated with NF279 prior to ATP
      superfusion or exposed to NF279 simultaneously with ATP. With a 10 s pre
      incubation period of NF279, IC(50) values of 19 nM and 1.62 microM were obtained
      for rat P2X(1) and P2X(3), respectively. Without pre-incubation, IC(50) values
      amounted to 2 microM and 85.5 microM for P2X(1) and P2X(3), respectively. For the
      non-desensitising rat P2X(2) receptor NF279 appeared to act as a competitive
      antagonist with an IC(50) value of 0.76 microM and a K(B) value of 0.36 microM,
      as derived from Schild analysis. P2X(4) receptors were the least sensitive
      subtypes for NF279 (IC(50)>300 microM). The antagonism was fully reversible at
      all P2X subtypes analysed. Our results indicate that NF279 is a potent P2X(1)
      receptor-selective and reversible antagonist.

PMID- 10963749
TI  - P2X(1) receptor membrane redistribution and down-regulation visualized by using
      receptor-coupled green fluorescent protein chimeras.
AB  - The P2X(1) purinergic receptor subtype occurs on smooth muscle cells of the vas
      deferens and urinary bladder where it is localized in two different size receptor
      clusters, with the larger beneath autonomic nerve terminal varicosities. We have
      sought to determine whether these synaptic-size clusters only form in the
      presence of varicosities and whether they are labile when exposed to agonists.
      P2X(1) and a chimera of P2X(1) and green fluorescent protein (GFP) were delivered
      into cells using microinjection, transient transfection or infection with a
      replication-deficient adenovirus. The P2X(1)-GFP chimera was used to study the
      time course of P2X(1) receptor clustering in plasma membranes and the
      internalization of the receptor following prolonged exposure to ATP. Both P2X(1)
      and P2X(1)-GFP clustered in the plasma membranes of Xenopus oocytes, forming
      patches 4-6 microm in diameter. Human embryonic kidney 293 (HEK293) cells,
      infected with the adenovirus, possessed P2X(1) antibody-labeled regions in the
      membrane colocalized with GFP fluorescence. The ED(50) for the binding of
      alpha,beta-methylene adenosine triphosphate (alpha,beta-meATP) to the P2X(1)-GFP
      chimera was similar to native P2X(1) receptors. ATP-generated whole-cell currents
      in oocytes or HEK293 cells expressing either P2X(1) or P2X(1)-GFP were similar.
      Exposure of HEK293 cells to alpha, beta-meATP for 10-20 min in the presence of 5
      microM monensin led to the disappearance of P2X(1)-GFP fluorescence from the
      surface of the cells. These observations using the P2X(1)-GFP chimera demonstrate
      that P2X(1) receptors spontaneously form synaptic-size clusters in the plasma
      membrane that are internalized on exposure to agonists.

PMID- 10963750
TI  - Moclobemide reduces intracellular pH and neuronal activity of CA3 neurones in
      guinea-pig hippocampal slices-implication for its neuroprotective properties.
AB  - Mechanisms underlying the neuroprotective properties of the weak MAO-A inhibitor
      moclobemide are not understood. Increasing evidence suggests that a moderate
      increase in intracellular free protons may contribute to neuroprotective
      properties due to a proton-mediated decrease in neuronal activity. Therefore, we
      studied effects of 10-700 microM moclobemide (i) on the intracellular pH (pH(i))
      of BCECF-AM loaded CA3 neurones as well as (ii) on spontaneous action potentials
      and epileptiform activity (induced by bicuculline-methiodide, caffeine, or 4
      aminopyridine) of CA3 neurones in the stratum pyramidale. Moclobemide
      concentrations of > or = 300 microM reversibly reduced the steady-state pH(i) by
      up to 0. 25 pH-units within 5-20 min. Simultaneously, the frequency of
      spontaneous action potentials and epileptiform discharges became depressed.
      Moclobemide also abolished 4-aminopyridine-induced GABA-mediated
      hyperpolarisations suggesting that the inhibitory and acidifying effects of
      moclobemide do not result from an amplification of the GABA system. The stronger
      MAO-A inhibitors clorgyline or pargyline (both 10 microM) mimicked the
      moclobemide-effects. Investigating effects on pH(i)-regulation we found that 700
      microM moclobemide impaired the recovery from intracellular acidification
      elicited by an ammonium prepulse which demonstrates an impairment of
      transmembrane acid extrusion. We suggest that the latter effect is responsible
      for the moderate decrease in the steady-state pH(i) which in turn reduced
      neuronal activity. This mechanism may substantially contribute to the
      neuroprotective properties of moclobemide.

PMID- 10963751
TI  - Nitric oxide regulates body temperature, neuronal activation and interleukin-1
      beta gene expression in the hypothalamic paraventricular nucleus in response to
      immune stress.
AB  - An immune challenge initiates a complex cascade of events in the body including
      important responses from the central nervous system. As nitric oxide (NO) has
      been implicated in the central regulation of neuroendocrine and autonomic
      responses, this study was performed to determine if NO regulates physiological
      responses, neuronal activation, and/or interleukin-1 beta (IL-1 beta) gene
      expression in the paraventricular nucleus of the rat hypothalamus (PVN) in
      response to intravenous endotoxin, lipopolysaccharide (LPS, 100 microg/kg).
      Intracerebroventricular injections of NO synthase (NOS) inhibitors (7
      nitroindazole sodium salt for neuronal NOS, N(G)-nitro-L-arginine for neuronal
      NOS and endothelial NOS, and aminoguanidine for inducible NOS) in LPS-treated
      rats showed that inhibition of NOS eliminated the drop in body temperature and
      led to increased neuronal activation in the PVN as assessed by
      immunohistochemistry for Fos-like immunoreactivity. Activation of NO-producing
      PVN neurons was also increased in these rats suggesting that NO influences
      neuronal NOS activity in PVN neurons. Finally, increased IL-1 beta gene
      expression in the PVN of LPS-treated rats receiving N(G)-nitro-L-arginine showed
      that NO regulates brain IL-1 beta gene expression. The results obtained with the
      NOS inhibitors support the hypothesis that NO produced from eNOS in the brain
      participates in temperature regulation, and inhibits PVN neuronal activity and IL
      1 beta gene expression during immune stress.

PMID- 10963752
TI  - Nitric oxide induces differentiation in the NB69 human catecholamine-rich cell
      line.
AB  - The nitric oxide (NO) donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), induced
      differentiation of human neuroblastoma NB69 cells to a dopamine phenotype, as
      shown by phase-contrast microscopy and tyrosine hydroxylase (TH)
      immunocytochemistry. NB69 cells were treated with 50 to 750 microM SNAP in serum
      free-defined medium for 24 h. SNAP treatment did not increase the number of
      necrotic or apoptotic cells. However, a decrease in the number of viable cells
      was observed at 750 microM SNAP. In addition, a decrease in (3)H-thymidine uptake
      was detected at the highest dose of SNAP. An increase in the antiapoptotic Bcl-2
      and Bcl-xL protein levels and a decrease in the proapoptotic Bax and Bcl-xS
      protein levels were also detected by Western blot analysis after SNAP treatment.
      At low doses (50-125 microM), SNAP induced an increase in catecholamine levels,
      (3)H-dopamine uptake, TH activity and monoamine metabolism, while a decrease in
      all these parameters was observed at high doses (250-750 microM). The TH protein
      content, analyzed by Western blot, remained unchanged in SNAP-treated cells
      throughout the range of doses studied, when compared with the control group. SNAP
      produced a dose-dependent decrease in the glutathione (GSH) content of the
      culture medium, without altering intracellular GSH. In addition, cGMP levels and
      nitrite concentration, measured in the supernatant of SNAP-treated cells,
      increased in a dose-dependent manner, as compared to control levels. The
      guanylate cyclase inhibitor lH-[1,2, 4]oxadiazolo[4,3a]quinoxaline-l-one (ODQ)
      did not revert the SNAP-induced effect on (3)H-dopamine uptake to control values.
      These results suggest that NO, released from SNAP, induces differentiation of
      NB69 cells and regulates TH protein at the post-transcriptional level through a
      cGMP-independent mechanism.

PMID- 10963753
TI  - Heterogeneous ligand-mediated Ca(++) responses at wt and mutant alpha(2A)
      adrenoceptors suggest multiple ligand activation binding sites at the alpha(2A)
      adrenoceptor.
AB  - Ligand:receptor interactions were analysed at wild-type, Asp(79)Asn and
      Thr(373)Lys alpha(2A) AR by measuring Ca(++) responses in the co-presence of a
      G(alpha 15) protein in CHO-K1 cells. (-)-Adrenaline displayed a time-dependent
      Ca(++) response with the following magnitude: wt alpha(2A) AR>Thr(373)Lys
      alpha(2A) AR>Asp(79)Asn alpha(2A) AR. The maximal amplitude of activation by d
      medetomidine and clonidine versus that of (-)-adrenaline was not affected by the
      Asp(79)Asn mutation, whereas it was significantly lower for both UK 14304 (-42%)
      and oxymetazoline (-35%). BHT 920 induced a higher Ca(++) response (+19%) at the
      Asp(79)Asn alpha(2A) AR. Some (atipamezole>BRL 44408=idazoxan approximately SKF
      86466>dexefaroxan) but not all (RX 811059 and RS 15385) of the putative alpha(2)
      AR antagonists tested also displayed partial agonist properties at the Asp(79)Asn
      alpha(2A) AR. At the Thr(373)Lys alpha(2A) AR, high-efficacy responses were
      produced by each of the agonists, whereas the putative antagonists showed the
      following rank order of maximal responses: BRL 44408>SKF 86466>atipamezole
      approximately idazoxan>dexefaroxan. The observed heterogeneity of Ca(++)
      responses produced by different ligands at wt and mutant alpha(2A) AR may be
      explained by assuming the existence of multiple ligand activation binding sites
      at the alpha(2A) AR.

PMID- 10963754
TI  - Chronic methamphetamine exposure decreases high affinity uptake function in
      norepinephrine afferents in the cerebellar cortex: an electrophysiological and
      electrochemical study.
AB  - It has been reported that chronic methamphetamine (MA) treatment decreases
      monoamine release in different brain regions. However, the clearance of
      norepinephrine (NE) after chronic MA intake is not clear. In the present study,
      we administered MA to Sprague-Dawley rats for 1 month. The animals were later
      anesthetized with urethane for electrophysiological recording. Previous studies
      have indicated that gamma-aminobutyric acid (GABA)-induced electrophysiological
      responses are enhanced by norepinephrine (NE) acting via postsynaptic beta
      adrenergic receptors. We found that local application of the NE high affinity
      uptake inhibitor desmethylimipramine (DMI) significantly potentiated GABA-induced
      electrophysiological depressions in cerebellar Purkinje neurons in control rats.
      In contrast, DMI did not augment GABA responses in rats chronically treated with
      MA for 1 month, or in rats withdrawn from MA for 7-14 days after a 1-month MA
      treatment. To further examine if DMI-induced GABA modulation is altered by post-
      or pre-synaptic mechanisms in chronic MA-treated rats, we examined the
      electrophysiological interaction of GABA and isoproterenol (ISO), a postsynaptic
      beta-adrenergic receptor agonist, in Purkinje neurons. We found that GABA-induced
      inhibition is potentiated by local application of ISO in both control and chronic
      MA rats, suggesting that the reduction in DMI/GABA interactions is probably not
      mediated through post-synaptic noradrenergic mechanisms. Presynaptic NE clearance
      was further examined using in vivo chronoamperometric methods. Extracellular NE
      levels in the cerebellar cortex were measured using Nafion-coated carbon fiber
      sensors. We found that local application of DMI inhibited NE clearance in control
      rats, but not in chronic MA animals, suggesting that presynaptic NE clearance is
      reduced after chronic MA treatment. In addition, NE levels in cerebellar tissue
      were measured using HPLC-ECD. The NE concentration was significantly decreased in
      chronic MA rats. Taken together, our data suggest that regulation of uptake by
      DMI at central noradrenergic nerve terminals is abnormal after chronic MA
      exposure.

PMID- 10963755
TI  - Effect of adenosine kinase, adenosine deaminase and transport inhibitors on
      striatal dopamine and stereotypy after methamphetamine administration.
AB  - The effect of adenosine kinase (AKA), adenosine deaminase (ADA) and transport
      inhibitors on the release of dopamine (DA) induced by methamphetamine (MTH) in
      rat striatum was assessed using in vivo microdialysis in freely moving rats. MTH
      injected in a dose of 3 x 5 mg/kg i.p. at 2-hour intervals produced a massive
      release of DA. This excessive release of DA was inhibited by the ADA inhibitor 2'
      deoxycoformycin (DCF), the AKA inhibitor 5'-iodotubercidin (IOT) and the
      adenosine uptake inhibitor dilazep (DIL), each of them given locally to the
      striatum via a microdialysis probe at a concentration of 100 microM. Perfusion
      with the same concentrations of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and
      5'-amino-5'-deoxyadenosine (NH(2)dAD), ADA and AKA inhibitors, respectively,
      induced a considerably weaker effect on DA release. The non-selective antagonist
      of adenosine A(1)/A(2A) receptor caffeine (75 microM) significantly prevented the
      inhibitory effect of DCF, IOT and DIL on the MTH-induced DA release.
      Intrastriatal administration of DCF, IOT and DIL (5 nmol/microl before each
      injection of MTH) inhibited the stereotypy induced by MTH. The striatal content
      of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid (HVA), decreased by MTH administration and measured 5 days after treatment
      with the toxin, was reversed by all the inhibitors at the order of potency as
      follows: IOT>DCF>DIL. Direct agonists of adenosine A(1) and A(1)/A(2A) receptors,
      N(6)-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA),
      respectively, given intrastriatally (5 nmol/microl) completely abolished the MTH
      induced stereotypy and the fall in the striatal content of DA, DOPAC and HVA. The
      above results show that augmentation of endogenous adenosine in rat striatum by
      inhibition of its metabolism or uptake-despite the differences in the efficacy of
      various inhibitors-may provide neuroprotection against a toxic action of MTH.

PMID- 10963756
TI  - Alkylation of rat dopamine transporters and blockade of dopamine uptake by EEDQ.
AB  - Effects of the alkylating agent EEDQ (N-ethoxycarbonyl-2-ethoxy-1, 2
      dihydroquinoline) on levels of dopamine transporter (DA(T)) and function were
      examined in caudate-putamen (CPu) tissue from rat brain. EEDQ produced profound,
      dose-dependent decreases in DA(T) binding in homogenates (IC(50)=78 microM) and
      frozen sections (IC(75)=200 microM) that were not reversed by washing. EEDQ also
      blocked uptake of [(3)H]DA in CPu synaptosomes (IC(50)=17 microM). However,
      single (10 mg/kg) or repeated administration of EEDQ in vivo (15 mg/kg/day x 3)
      did not alter DA(T) levels or DA uptake in CPu. Pretreatment of rats with alpha
      methyl-p-tyrosine and reserpine to deplete endogenous dopamine also failed to
      lower DA(T) levels in CPu after injections of EEDQ. EEDQ is an effective
      alkylating agent for DA(T) in vitro, but not to evaluate metabolic turnover or
      function of DA(T) in vivo. The results encourage development of selective and in
      vivo-active DA(T)-alkylating agents.

PMID- 10963757
TI  - The anticonvulsant, lamotrigine decreases spontaneous glutamate release but
      increases spontaneous GABA release in the rat entorhinal cortex in vitro.
AB  - It has been suggested that the anticonvulsant effect of lamotrigine resides with
      it's ability to block voltage gated Na-channels at presynaptic sites, thus
      stabilizing the presynapse, and, consequently, reducing the release of synaptic
      transmitters. Neurochemical studies have shown that it can inhibit the veratrine
      stimulated release of the excitatory transmitter, glutamate from cortical tissue,
      but that at slightly higher concentrations it also reduces the release of the
      inhibitory transmitter, GABA. In the present study we examined the effect of the
      drug on the release of these transmitters at synapses in the rat entorhinal
      cortex, using the whole-cell patch clamp technique to record spontaneous
      excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs). Lamotrigine
      reduced the frequency, but not the amplitude of spontaneous EPSCs. This clearly
      indicated a presynaptic effect to reduce the release of glutamate. However, the
      same effect was observed when we tested the drug on miniature EPSCs, recorded in
      the presence of TTX and Cd, showing that blockade of Na-channels or Ca-channels
      was not a prerequisite for inhibition of glutamate release. In contrast to it's
      effects on EPSCs, lamotrigine increased both the frequency and amplitude of
      spontaneous IPSCs, suggesting that the drug was acting presynaptically to enhance
      GABA release. Again, similar effects were seen with miniature IPSCs recorded in
      TTX. These opposite effects of lamotrigine on glutamate and GABA release are
      similar to those we have reported previously with phenytoin, and suggest that
      reciprocal modulation of the background release of the major excitatory and
      inhibitory transmitters may be a significant factor in dampening excitability in
      pathologically hyperexcitable cortical networks.

PMID- 10963758
TI  - Effects of compounds acting on GABA(B) receptors in the pentylenetetrazole
      kindling model of epilepsy in mice.
AB  - The involvement of GABA(B) receptors in the behavioural and epileptic
      electrocortical discharges occurring in chemical kindling induced by repeated
      treatments with a subconvulsant dose of pentylenetetrazole (25 mg/kg i.p.) has
      been investigated in CD1 mice. Behavioural and electrocorticographic epileptic
      seizures following kindling induced by pentylenetetrazole (25 mg/kg i.p.) were
      attenuated or completely antagonized in a dose-dependent manner by the GABA(B)
      receptor agonist R-baclofen (2 and 6 mg/kg) whilst the GABA(B) receptor
      antagonist 3-amino-propyl-diethoxy-methyl-phosphinic acid (CGP 35348, 25, 50 or
      100 mg/kg) and 3-[1-(S)-(3, 4-dichloro-phenyl-ethyl]amino-2-(S)-hydroxy-propyl
      benzyl-phosphinic acid (CGP 55845A, 10 or 20 mg/kg) produced a more rapid
      development of kindling and an increase in behavioural and electrocorticographic
      epileptic changes. In addition, all GABA(B) receptor antagonists were able to
      induce an increase in Fos and Jun protein expression in pentylenetetrazole (25
      mg/kg i.p.) treated mice whilst the GABA(B) receptor agonist R-baclofen (2 or 6
      mg/kg) attenuated the expression of Fos and Jun protein, at cortical and limbic
      structures. In order to study the persistence of changes induced by
      pentylenetetrazole kindling, different groups of mice were rechallenged with a
      kindling stimulus 15 or 30 days after withdrawal from the last injection of
      vehicle+pentylenetetrazole, R-baclofen+pentylenetetrazole or GABA(B) receptor
      antagonists+pentylenetetrazole. The groups receiving GABA(B) receptor
      antagonists+pentylenetetrazole showed a higher incidence of seizures following
      the kindling stimulus than mice receiving vehicle+pentylenetetrazole whilst
      animals treated with R-baclofen were protected from the kindling stimulus. The
      different effects observed following repeated treatment with the GABA(B) receptor
      agonist and antagonist used revealed that GABA(B) receptors are able to affect
      the development of the epileptic kindling state induced by pentylenetetrazole.

PMID- 10963759
TI  - Increased expression of endoplasmic reticulum stress proteins following chronic
      valproate treatment of rat C6 glioma cells.
AB  - The anticonvulsant sodium valproate has been shown to be an effective treatment
      for bipolar disorder, however, its precise mechanism of action has yet to be
      determined. It has been suggested that adaptational changes in gene expression
      are critical for valproate's prophylactic effects. Previous studies in our lab
      have shown that one gene that may be regulated by valproate is the 78-kilodalton
      glucose-regulated protein (GRP78). We report that treatment of rat C6 glioma
      cells with valproate can also increase the expression of additional endoplasmic
      reticulum stress proteins, GRP94 and calreticulin. All three proteins showed
      similar concentration-dependent increases in messenger RNA abundance. Chronic
      (seven days) treatment significantly increased GRP78 and GRP94 messenger RNA
      expression, whereas calreticulin expression increased after both acute and
      chronic treatment. Increases in mRNA expression corresponded to a similar
      increase in protein expression. The roles of GRP78, GRP94 and calreticulin as
      molecular chaperones and calcium binding proteins, suggest that these results
      might have functional relevance to the therapeutic action of valproate.

PMID- 10963760
TI  - Effects of strain and serotonergic agents on prepulse inhibition and habituation
      in mice.
AB  - Neural sensorimotor gating mechanisms prevent the interruption of ongoing
      information processing routines by ensuing stimuli to permit mental integration
      and adaptive behavior. Prepulse inhibition (PPI), an operational measure of
      sensorimotor gating, is now being investigated using murine models to exploit
      transgenic and "knockout" technology. The present studies were undertaken to
      evaluate potential murine strain differences in the effects of serotonergic drugs
      on PPI and habituation. Two strains used most often as a genetic background for
      transgenic or knockout manipulations, C57BL/6 and 129Sv, and the outbred ICR
      strain were used. We assessed the effects of the 5-HT(1A/1B) agonist 5-methoxy
      3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969), the 5-HT(1A) agonist 8
      hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT(2A/2C) agonist (+/-)2,5
      dimethoxy-4-methylamphetamine (DOM), and the serotonin releaser (+)3, 4
      methylenedioxy-N-methylamphetamine (MDMA) on PPI and habituation of acoustic
      startle in the three strains. C57BL/6 mice exhibited lower baseline PPI levels
      than 129Sv and ICR mice, and 129Sv mice habituated less than C57BL/6 and ICR
      mice. MDMA decreased PPI in C57BL/6 and ICR, but not 129Sv mice, and RU24969
      disrupted habituation in C57BL/6 and 129Sv, but not ICR mice. Lastly, RU24969
      decreased and 8-OH-DPAT increased PPI across all strains, although qualitative
      differences were observed. Thus, both baseline and serotonergic drug-induced
      effects on murine PPI and habituation are strain-dependent.

PMID- 10963761
TI  - Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain
      related behavior.
AB  - Our recent study demonstrated that ginsenosides had antinociceptive effects by
      reducing some types of pain-related behavior in mice (Yoon et al., 1998.
      Ginsenosides induce differential antinociception and inhibit substance P-induced
      nociceptive response in mice. Life Science 62, PL319-PL325). In the present study
      we further investigated whether ginsenosides produce antinociceptive effects
      through an action at central or peripheral site(s) and whether these effects are
      mediated by the opioid system. Intraperitoneally injected ginsenosides suppressed
      in a dose-dependent manner the pain-related behavior produced by capsaicin
      injection into the plantar surface of the hind paw; the ED(50) was 49 mg/kg [26
      92 mg/kg, 95% confidence interval (C.I.)]. Intrathecally or
      intracerebroventricularly administered ginsenosides also suppressed the capsaicin
      induced pain-related behavior in a dose-dependent manner; the ED(50)s were 1.72
      mg/kg (0.8-3.72 mg/kg, 95% C.I.) and 1. 48 mg/kg (0.8-2.6 mg/kg, 95% C.I.),
      respectively. On the other hand, subcutaneously injected ginsenosides to the
      plantar surface prior to the capsaicin injection did not alter the pain-related
      behavior. Naloxone pretreatment was without effect in blocking the
      antinociceptive effect of intrathecally administered ginsenosides.
      Intraperitoneally injected ginsenosides also did not significantly affect the
      motor response of animals. These results suggest that ginsenosides produce
      antinociceptive effects through their action at the spinal and/or supraspinal
      site(s), not at nociceptors in the periphery. In addition, the results suggest
      that the antinociceptive effects are not mediated by opioid receptors.

PMID- 10963762
TI  - Capsaicin induces a slow inward current which is not mediated by substance P in
      substantia gelatinosa neurons of the rat spinal cord.
AB  - Whole-cell voltage-clamp techniques were employed to investigate a capsaicin
      induced current in substantia gelatinosa (SG) neurons in the dorsal horn of adult
      rat spinal cord slices. Bath-applied capsaicin (2 microM) for 30 s activated a
      slow excitatory current having an amplitude of 21.3+/-6.3 pA and a duration of
      93+/-13 s (n=10; V(H)=-70 mV). This capsaicin current was compared in amplitude
      under various conditions among different SG neurons. After either neonatal
      capsaicin treatment or sciatic-nerve transection, by which C-afferent fibers are
      known to degenerate, this capsaicin current was reduced in amplitude to 5.0+/-3.5
      pA (n=8) or 4.5+/-2.3 pA (n=6), respectively. A non-N-methyl-D-aspartate (NMDA)
      receptor antagonist, CNQX (10 microM), depressed greatly the capsaicin current to
      4.0+/-1.3 pA (n=9). On the other hand, this current had an amplitude of 14.4+/
      2.7 pA (n=10) in the presence of an NMDA-receptor antagonist, AP-5 (50 microM);
      this value was not significantly different from that in the control (P>0.05).
      Substance P (SP; 1-2 microM) superfused for 2 min had no detectable effect on all
      SG neurons examined (n=7). After SP washout, however, these cells exhibited a
      capsaicin current (22.8+/-12.1 pA); this current persisted in the presence of a
      neurokinin-1 receptor antagonist, L-732,138 (1 microM; 19.8+/-3.5pA, n=9). The
      capsaicin current was not abolished by an intracellular dialysis with GDP-beta-S
      (1 mM; 20. 2+/-2.4 pA, n=9) which inhibited a baclofen (10 microM) response
      mediated by the G-protein-coupled GABA(B) receptor. These results indicate that
      the capsaicin-induced current is mediated through the activation of C-fibers by
      non-NMDA receptors. This mechanism in SG neurons is different from that known in
      neurons in other laminae of the dorsal horn that is thought to be a direct action
      of SP released from C-fibers. This current in SG neurons would contribute to the
      pain sensation caused by capsaicin.

PMID- 10963763
TI  - Direct inhibition of glycine receptors by genistein, a tyrosine kinase inhibitor.
AB  - Genistein, a tyrosine kinase inhibitor, has been widely used to examine potential
      effects of protein tyrosine kinase (PTK)-mediated regulation of receptor/channel
      function. Alteration of ion channel function in the presence of genistein has
      typically led to the conclusion that PTK regulates the activity of the channel
      under investigation. In the present report, we have assessed the possibility that
      genistein directly inhibits the glycine receptor, independent of effects on
      protein tyrosine kinase. Coapplication of genistein with glycine reversibly
      inhibited the strychnine-sensitive, glycine-activated current recorded from
      hypothalamic neurons. The time course of genistein action was rapid (within ms).
      Equilibration of genistein in the intracellular solution did not affect the
      ability of extracellularly applied genistein to inhibit the glycine response.
      Glycine concentration-response profiles generated in the absence and presence of
      genistein indicated the block was due to non-competitive antagonism. The
      genistein effect also displayed voltage-dependence. Daidzein, an analog of
      genistein that does not block protein kinases, also inhibited glycine-activated
      current. Coapplication of lavendustin A, a specific inhibitor of PTK, had no
      effect on the glycine response. Our results demonstrate that the tyrosine kinase
      inhibitor genistein has a direct inhibitory effect on glycine receptors that is
      not mediated via inhibition of PTK.

PMID- 10963764
TI  - Effects of caffeine and paracetamol alone or in combination with acetylsalicylic
      acid on prostaglandin E(2) synthesis in rat microglial cells.
AB  - Paracetamol has mild analgesic and antipyretic properties and is, along with
      acetylsalicylic acid, one of the most popular "over the counter" analgesic
      agents. However, the mechanism underlying its clinical effects is unknown.
      Another drug whose mechanism of action is unknown is caffeine, which is often
      used in combination with other analgesics, augmenting their effect. We
      investigated the inhibitory effect of paracetamol and caffeine on
      lipopolysaccharide (LPS)-induced cyclooxygenase (COX)- and prostaglandin (PG)E(2)
      synthesis in primary rat microglial cells and compared it with the effect of
      acetylsalicylic acid, salicylic acid, and dipyrone. Furthermore, combinations of
      these drugs were used to investigate a possible synergistic inhibitory effect on
      PGE(2)-synthesis. Both paracetamol (IC(50)=7.45 microM) and caffeine (IC(50)=42.5
      microM) dose-dependently inhibited microglial PGE(2) synthesis. In combination
      with acetylsalicylic acid (IC(50)=3.12 microM), both substances augmented the
      inhibitory effect of acetylsalicylic acid on LPS-induced PGE(2)-synthesis.
      Whereas paracetamol inhibited only COX enzyme activity, caffeine also inhibited
      COX-2 protein synthesis. These results are compatible with the view that the
      clinical activity of paracetamol and caffeine is due to inhibition of COX.
      Furthermore, these results may help explain the clinical experience of an
      adjuvant analgesic effect of caffeine and paracetamol when combined with
      acetylsalicylic acid.

PMID- 10963765
TI  - Effect of brefeldin A on acetylcholine release from glioma C6BU-1 cells.
AB  - The glial C6BU-1 cell line, loaded with acetylcholine can release this
      neurotransmitter. This study was aimed at determining whether disruption of the
      Golgi-vesicular traffic by brefeldin A would change the acetylcholine release
      from these cells and affect proteins involved in transmitter release like the 15
      kDa proteolipid, common to V-ATPase and mediatophore. Cells were treated for 24
      or 36 h with brefeldin A (35.7 microM). The observed changes in cell morphology
      were typical for brefeldin A treated cells in which protein membrane supply has
      been stopped. Inhibition of membrane protein supply was confirmed in the present
      work. Moreover, the 15 kDa proteolipid also decayed to a very low level in the
      cell membrane fraction. The release of acetylcholine evoked by a calcium
      challenge and a calcium ionophore, or by electrical pulses decreased markedly.
      The life time of the release mechanism was of the order of 36 h and half decayed
      in 24 h. In addition, the electrically evoked release became much shorter.
      Considering that C6BU-1 cells are able to release large amounts of ACh and their
      membranes contain a sizeable amount of the 15 kDa proteolipid, these results
      suggest that this proteolipid may be one of the proteins forming the membrane
      complex responsible for transmitter release, at least in these cells.

PMID- 10963766
TI  - Mechanisms and variables determining the cardiopulmonary responses to hypoxia

PMID- 10963767
TI  - Ventrolateral pons mediates short-term depression of respiratory frequency after
      brief hypoxia.
AB  - The respiratory response to hypoxia is dynamic in the adult anesthetized Sprague
      Dawley rat. Hypoxia elicits acute increases in both tidal volume (VT) and
      respiratory frequency (fR) followed by short-term increases in VT and short-term
      decreases in fR. After brief hypoxia (<1 min), recovery of the breathing pattern
      is again dynamic, where both VT and fR decrease immediately, but where VT remains
      above, and fR drops below, baseline. These acute changes are followed by a short
      term progressive decrease in VT and increase in fR to baseline. We have
      identified a potential neural mechanism that depends on the integrity of the
      ventrolateral (vl) pons. Our studies show that: (a) blockade of activity in the
      vl pons prevents the short-term decrease in fR after hypoxia (b) stimulation of
      the vl pons decreases fR, and (c) vl pontine expiratory neurons are activated
      after hypoxia. These neurons may not be acting through alpha(2) -adrenergic
      receptors, but their effect does depend on NMDA-type receptor function. We
      conclude that the vl pons is a critical element in the pontomedullary network
      that generates and modulates the fR response to acute hypoxia.

PMID- 10963768
TI  - Excitation of phrenic and sympathetic output during acute hypoxia: contribution
      of medullary oxygen detectors.
AB  - Severe brain hypoxia results in respiratory excitation and an increase in
      sympathetic nerve activity. Respiratory excitation takes the form of gasping
      which is characterized by an abrupt onset, high amplitude, short duration burst
      of inspiratory activity. Recent evidence suggests that centrally-mediated hypoxic
      respiratory and sympathetic excitation may result from direct hypoxic stimulation
      of discrete hypoxia chemosensitive sites in the medulla. Thus, medullary regions
      involved in the generation and modulation of respiratory and sympathetic
      vasomotor output may contain neurons which function as central oxygen detectors,
      acting as medullary analogs to the peripheral (arterial) chemoreceptors. This
      review focuses on the medullary sites and mechanisms proposed to mediate hypoxic
      respiratory and sympathetic excitation in anesthetized, chemodeafferented
      animals, and provides the evidence suggesting a role for central oxygen detectors
      in the control of breathing and sympathetic vasomotor output.

PMID- 10963769
TI  - Respiratory neural activity during long-term facilitation.
AB  - Intermittent hypoxia results in a long-term facilitation (LTF) of respiratory
      efferent activity. The studies reviewed here presented data from both
      anesthetized and decerebrate, paralyzed, vagotomized, artificially ventilated
      adult cats. Multiple arrays of tungsten microelectrodes were used to record the
      concurrent responses of brain stem neurons that contribute to respiratory motor
      pattern generation. Spike trains were analyzed with firing rate histograms,
      peristimulus time histograms, cycle triggered histograms, spike triggered
      averages with multiunit phrenic efferent activity, cross correlation histograms,
      joint peristimulus time histograms and the gravity method. These studies
      addressed several hypotheses. (1) There is parallel processing of input from
      carotid chemoreceptors to the brain stem. (2) Respiratory related midline neurons
      are involved in the induction and maintenance of LTF. (3) There is a change in
      effective connectivity of brain stem neurons with LTF. (4) Neural networks
      involved in the induction and maintenance of LTF have patterns of synchrony that
      recur with a frequency greater than expected by chance.

PMID- 10963770
TI  - Long term facilitation of phrenic motor output.
AB  - Episodic hypoxia or electrical stimulation of carotid chemoafferent neurons
      elicits a sustained, serotonin-dependent augmentation of respiratory motor output
      known as long term facilitation (LTF). The primary objectives of this paper are
      to provide an updated review of the literature pertaining to LTF, to investigate
      the influence of selected variables on LTF via meta-analysis of a large data set
      from LTF experiments on anesthetized rats, and to propose an updated mechanism of
      LTF. LTF has been demonstrated in anesthetized and awake experimental
      preparations, and can be evoked in some human subjects during sleep. The
      mechanism underlying LTF requires episodic chemoafferent stimulation, and is not
      elicited by similar cumulative durations of sustained hypoxia. Meta-analysis of
      phrenic nerve responses following episodic hypoxia in 63 experiments on
      anesthetized rats (conducted by four investigators over a period of several
      years) indicates that phrenic LTF magnitude correlates with peak phrenic
      responses during hypoxia and hypercapnia, but not with the level of hypoxia
      during episodic exposures. Potential mechanisms underlying these relationships
      are discussed, and currently available data are synthesized into an updated
      mechanistic model of LTF. In this model, we propose that LTF arises predominantly
      from episodic activation of serotonergic receptors on phrenic motoneurons,
      activating intracellular kinases and, thus, phosphorylating and potentiating
      ionic currents associated with the glutamate receptors that mediate respiratory
      drive.

PMID- 10963771
TI  - Neural structures that mediate sympathoexcitation during hypoxia.
AB  - The sympathetic adjustments triggered by acute mild hypoxia (sympathetic
      chemoreflex) are initiated by activation of peripheral chemoreceptors whereas
      more severe hypoxia activates the sympathetic outflow via direct effects on the
      brainstem. In both cases the rostral ventrolateral medulla (RVLM) plays a
      critical role in these responses. The first part of this review briefly describes
      the general input-output properties of the presympathetic neurons of RVLM before
      focusing on the neural pathways leading to their excitation in response to
      peripheral chemoreceptor stimulation. The extent to which the central respiratory
      network contributes to the sympathetic chemoreflex is then discussed before
      briefly alluding to its role in obstructive sleep apnea and other pathologies.
      The second half of the review examines the direct effects of hypoxia on RVLM
      neurons and whether this region and the presympathetic neurons in particular
      qualify as a physiological central oxygen sensor. The literature is also examined
      in the context of cerebral ischemia, the Cushing response and the genesis of
      certain forms of hypertension.

PMID- 10963772
TI  - Effects of hypoxia on sympathetic neural control in humans.
AB  - This special issue is principally focused on the time domain of the adaptive
      mechanisms of ventilatory responses to short-term, long-term and intermittent
      hypoxia. The purpose of this review is to summarize the limited literature on the
      sympathetic neural responses to sustained or intermittent hypoxia in humans and
      attempt to discern the time domain of these responses and potential adaptive
      processes that are evoked during short and long-term exposures to hypoxia.

PMID- 10963774
TI  - Respiratory responses to single and episodic hypoxia during development:
      mechanisms of adaptation.
AB  - The respiratory responses of the developmental subject to single and repeated
      episodes of hypoxia are distinct. During a single exposure, the fetus responds
      with an arrest of breathing activity, and the neonate, with excitation followed
      by depression (the biphasic response). Mechanisms under active consideration
      include chemosensory resetting, hypometabolism, prevalence of inhibitory
      neurotransmitter/modulator influence, and supramedullary regulation of control
      functions. When exposed to recurrent episodic hypoxia, neonates respond with
      relative hypoventilation, i.e. tolerance to a subsequent hypoxic stimulus.
      Whereas the investigation of processes responsible for this tolerance is at its
      infancy, studies using chronic hypoxia appear to be a useful guide. So far,
      altered interstitial neuromodulator levels and central markers of programmed
      neuronal death are harbingers of future research in this field. The clarification
      of the mechanisms involved in response to recurrent episodic hypoxia during
      development will be of fundamental value and may be useful for the eventual
      treatment and/or prevention of harmful central respiratory-related processes.

PMID- 10963773
TI  - Chronic-intermittent hypoxia: a model of sympathetic activation in the rat.
AB  - This review focuses upon the development of a small animal model that
      incorporates exposure to chronic-intermittent hypoxia to produce systemic
      hypertension similar to that experienced by humans with the obstructive sleep
      apnea syndrome. It has been suggested that experimentally-induced hypertension,
      like human hypertension, is due to activation of the sympathetic nervous system.
      That hypothesis is supported by physiological studies carried out in humans with
      obstructive sleep apnea as well as in animals exposed to chronic-intermittent
      hypoxia. Furthermore, recent anatomical studies of exposed animals strongly
      suggested that activation was widespread and included cortical and brainstem
      components of the sympathetic system. Such findings, while illustrating the
      complexity of modeling human disease in animals, also demonstrate the heuristic
      value of chronic-intermittent hypoxia as an experimental approach.

PMID- 10963775
TI  - Developmental influences on carotid body responses to hypoxia.
AB  - Progress on our understanding of the mechanisms by which ventilatory responses to
      hypoxia and hypercapnia mature following birth will be reviewed. New reports have
      broadened the current understanding of these mechanisms, especially those
      relating to maturation of the arterial chemoreceptors in the carotid body.
      However, a clear understanding of the physiologic, morphologic, neurochemical and
      molecular developmental events remains elusive. Of particular interest is the
      change in carotid body sensitivity to oxygen in the first days following birth.
      Further, perinatal hypoxia or hyperoxia results in blunted hypoxic
      chemosensitivity in premature infants with chronic lung disease and in various
      animal models. Hence, cellular and molecular mechanisms altering the normal
      maturational progression will also be discussed.

PMID- 10963776
TI  - Signaling pathways of the acute hypoxic ventilatory response in the nucleus
      tractus solitarius.
AB  - The nucleus tractus solitarii (nTS) provides the initial central synaptic relay
      to peripheral chemoreceptor afferent inputs elicited by changes in oxygen
      tension. Insofar, the overall cumulative evidence pointing towards the N-methyl-D
      aspartate (NMDA) glutamate receptor as the critical receptor underlying the early
      component of the hypoxic ventilatory response (HVR) is reviewed in detail. In
      addition, we will present recent findings supporting a role for platelet-derived
      growth factor (PDGF) beta receptor activation in modulation of the late phase of
      HVR. This evidence underscores the proposal of a working model for intracellular
      signaling pathways, downstream to the NMDA glutamate and PDGF-beta receptors in
      nTS neurons, which may contribute to both the ventilatory characteristics of the
      acute hypoxic response and to subsequently occurring functional adaptations and
      synaptic plasticity phenomena.

PMID- 10963777
TI  - Central nervous system mechanisms of ventilatory acclimatization to hypoxia.
AB  - Ventilatory acclimatization to hypoxia is the time-dependent increase in
      ventilation that occurs with chronic exposure to hypoxia. Despite decades of
      research, the physiological mechanisms that increase the hypoxic ventilatory
      response during chronic hypoxia are not well understood. This review focuses on
      adaptations within the central nervous system (CNS) that increase the hypoxic
      ventilatory response. Although an increase in CNS responsiveness had been
      proposed many years ago, only recently has strong experimental evidence been
      provided for an increase in the CNS gain in the rat, which has proved to be a
      good model of VAH in humans. Within the CNS, several neuroanatomical sites could
      be involved as well as changes in various neurotransmitters, neuromodulators or
      signalling mechanisms within any of those sites. Lastly, adaptations within the
      CNS could involve both direct effects of decreased P(O(2)) and indirect effects
      of increased afferent nerve activity due to chronic stimulation of the peripheral
      arterial chemoreceptors.

PMID- 10963778
TI  - Carotid body mechanisms in acclimatization to hypoxia.
AB  - Most studies oriented toward examining mechanisms increasing carotid body (CB)
      sensitivity to hypoxia during ventilatory acclimatization (VAH) have focussed on
      the role of known neuromodulators of CB function. Two general categories of the
      neuromodulatory agents studied most extensively could be considered: those
      thought to be primarily inhibitory to CB function: dopamine, norepinephrine,
      nitric oxide and those thought to be primarily excitatory: substance P,
      endothelin. There is evidence that these putative inhibitory agents are up
      regulated in the first weeks of chronic hypoxia and that substance P is down
      regulated. All these changes would favor a decrease in CB sensitivity to hypoxia.
      There are data suggesting that CB endothelin activity is up-regulated in rats
      subjected to chronic hypoxia, a direction suggesting increased CB sensitivity to
      hypoxia. Dopamine may have an excitatory as well as an inhibitory role on the CB,
      but there is not yet evidence to indicate that an excitatory role for DA exists
      in chronic hypoxia. Ion channel studies of type I CB cells suggest increased
      excitability after prolonged hypoxia. The role of excitatory CB nicotinic
      receptors and putative serotonin type 3 receptors should be examined further for
      their potential role in VAH. It is suggested that a balance of excitatory and
      inhibitory modulation is responsible for increased CB sensitivity to hypoxia
      during VAH.

PMID- 10963779
TI  - Inheritance of ventilatory behavior in rodent models.
AB  - Studies in mice and rats support the hypothesis that ventilation and its
      components (frequency and tidal volume) are determined to a significant extent by
      genetic mechanisms. The question can no longer be 'is there a genetic effect?'
      but rather 'how strong is the genetic component?' and 'what genes are involved?'
      The computational analyses of selectively bred animals now offer powerful tools
      to begin to dissect the genetic factors that track with ventilatory traits.
      Control of the conditions in the colony and in the laboratory are keys to
      reducing the environmental 'noise' and increasing the likelihood of detecting
      gene loci that correlate quantitatively with phenotype values before and during
      the response to chemosensory challenges. Knowing the chromosomal location of
      genes for ventilation will then permit the identification of proteins systems
      responsible for the structural and functional components for respiration.

PMID- 10963780
TI  - Comparative human ventilatory adaptation to high altitude.
AB  - Studies of ventilatory response to high altitudes have occupied an important
      position in respiratory physiology. This review summarizes recent studies in
      Tibetan high-altitude residents that collectively challenge the prior consensus
      that lifelong high-altitude residents ventilate less than acclimatized newcomers
      do as the result of acquired 'blunting' of hypoxic ventilatory responsiveness.
      These studies indicate that Tibetans ventilate more than Andean high-altitude
      natives residing at the same or similar altitudes (PET[CO(2)]) in Tibetans=29.6+/
      0.8 vs. Andeans=31.0+/-1.0, P<0.0002 at approximately 4200 m), a difference which
      approximates the change that occurs between the time of acute hypoxic exposure to
      once ventilatory acclimatization has been achieved. Tibetans ventilate as much as
      acclimatized newcomers whereas Andeans ventilate less. However, the extent to
      which differences in hypoxic ventilatory response (HVR) are responsible is
      uncertain from existing data. Tibetans have an HVR as high as those of
      acclimatized newcomers whereas Andeans generally do not, but HVR is not
      consistently greater in comparisons of Tibetan versus Andean highland residents.
      Human and experimental animal studies demonstrate that inter-individual and
      genetic factors affect acute HVR and likely modify acclimatization and
      hyperventilatory response to high altitude. But the mechanisms responsible for
      ventilatory roll-off, hyperoxic hyperventilation, and acquired blunting of HVR
      are poorly understood, especially as they pertain to high-altitude residents.
      Developmental factors affecting neonatal arterial oxygenation are likely
      important and may vary between populations. Functional significance has been
      investigated with respect to the occurrence of chronic mountain sickness and
      intrauterine growth restriction for which, in both cases, low HVR seems
      disadvantageous. Additional studies are needed to address the various components
      of ventilatory control in native Tibetan, Andean and other lifelong high-altitude
      residents to decide the factors responsible for blunting HVR and diminishing
      ventilation in some native high-altitude residents.

PMID- 10963781
TI  - Carbohydrate-deficient transferrin and sialidase levels in coronary heart
      disease.
AB  - Transferrin is a N-glycosylated glycoprotein and plays an important role in iron
      transport from sites of absorption and storage to sites of utilization. The main
      component of normal serum transferrin contains two biantennary glycans, each
      consisting of 2 mol of sialic acid (Tetrasialo transferrin). Normal serum also
      contains small amounts of tri- and disialotransferrin. We have undertaken this
      study to investigate the levels of serum carbohydrate-deficient transferrin
      (Desialotransferrin) and sialidase levels in patients with coronary heart
      disease. In patient group, serum desialotransferrin and sialidase levels were
      found to be significantly higher than control group (p < 0.01 and p < 0.001,
      respectively). We conclude that increased activity of sialidase may be
      responsible for increased desialotransferrin in patients with coronary heart
      disease. Serum desialotransferrin levels may be useful critaria to diagnosis and
      pathogenesis of coronary heart disease.

PMID- 10963782
TI  - The allele frequency of mutations in four genes that confer enhanced
      susceptibility to venous thromboembolism in an unselected group of New York State
      newborns.
AB  - The frequencies of Factor V G1691A (FVL), prothrombin (PT) G20210A,
      5'10'methylenetetrahydrofolate reductase (MTHFR) C677T, and methionine synthase
      (MS) A2756G (four mutations associated with an increased risk of venous
      thromboembolism [VTE]) were determined in a sample of approximately 1500 New York
      State residents. Dried blood spots from approximately equal numbers of
      Caucasians, African-Americans and Hispanics were anonymously obtained from the
      New York State Department of Health Newborn Screening Program. Following PCR
      amplification of dried blood spot DNA, allele-specific oligonucleotide
      hybridization was used to detect mutant alleles. The total number of individuals
      at increased genetic risk for VTE was 271 (17.5%) of the 1553 persons tested.
      Increased genetic risk was defined as the heterozygous state for FVL or PT and
      the homozygous state for the MTHFR or MS polymorphisms. Sixteen individuals had
      more than one genetic risk factor. The MS gene variant allele frequencies for
      African-Americans and Hispanics are the first to be reported. This report also
      provides an estimate of the variant PT allele in the largest group of Hispanics
      studied to date.

PMID- 10963783
TI  - A new therapeutic option by subcutaneous recombinant hirudin in patients with
      heparin-induced thrombocytopenia type II: a pilot study.
AB  - We prospectively studied 15 patients suffering from acute heparin-induced
      thrombocytopenia (HIT) type II with and without thromboembolic events and 4
      patients with anamnestically known HIT type II recurrently requiring
      thromboprophylaxis in order to develop new therapeutic strategies by subcutaneous
      recombinant hirudin administration. Patients with acute venous or arterial
      thromboembolism were treated with aPTT-controlled intravenous (mean: 19.3 days)
      followed by subcutaneous r-hirudin (mean: 22.5 days). Patients without
      thromboembolism were treated with subcutaneous r-hirudin (mean: 25.9 days). Four
      patients were readmitted to subcutaneous r-hirudin (mean: 32 days). When r
      hirudin was administered subcutaneously following intravenous treatment, mean
      baseline (prior to the injection) and mean peak (1.5-2.5 hours after the
      injection) aPTT ratios were 1.1 (+/-0.2) to 1.7 (+/-0.48) and 2. 48 (+/-0.43) to
      2.52 (+/-0.4) times normal value, respectively. Mean baseline and mean peak ECT
      ratios were 1.2 (+/-0.12) to 1.9 (+/-0. 22) and 2.2 (+/-0.25) to 2.6 (+/-0.11)
      times the upper normal value, respectively. When r-hirudin was initially
      administered subcutaneously, mean baseline and mean peak aPTT ratios were 1.41
      (+/-0.25) to 1.61 (+/-00.28) and 1.88 (+/-0.26) to 2.06 (+/-0.09) times the
      normal value, respectively. Mean baseline and mean peak ECT ratios were 1.25 (+/
      0.2) to 1.5 (+/-0.38) and 2.01 (+/-0.21) to 2.23 (+/-0.25) times the upper limit
      of normal, respectively. Patients who received recurrent subcutaneous r-hirudin
      had mean baseline and peak aPTT values of 1.5 (+/-0.35) to 1.75 (+/-0.156) and
      2.0 (+/-0.33) to 2.1 (+/-0.18) times the normal value, respectively. Mean
      baseline and peak ECT ratios were 1.3 (+/-0.26) to 1.65 (+/-0.09) and 1.94 (+/
      0.256) to 2.7 (+/-0.23) times the upper limit of normal, respectively. The
      overall cumulative incidence of r-hirudin antibodies was 12/19 (63%) with a
      significant accumulation of r-hirudin in antibody-positive patients compared to
      antibody-negative patients (p<0.05). No patient suffered a new thromboembolic or
      major bleeding event. Subcutaneous administration of recombinant hirudin provides
      a long-term thromboprophylaxis regimen in HIT type II patients after passivation
      of acute thromboembolism.

PMID- 10963784
TI  - Protective effect of defibrotide on perfusion induced endothelial damage.
AB  - In the present study, in vitro effects of Defibrotide (D) on perfusion-induced
      changes in the morphology of endothelium were investigated by scanning (SEM) and
      transmission (TEM) electron microscope. Human umbilical cord veins were incubated
      or perfused with platelet-rich plasma alone (PRP) or platelet-rich plasma with
      Defibrotide (PRP+D) at 3ml/min or 14ml/min and the changes observed were
      compared. SEM examination of luminal surfaces demonstrated that perfusion with
      high flow rates may damage endothelial cells and lead to morphological changes
      which may be prevented by the presence of Defibrotide in the perfusate. Also, the
      marked reduction in the number of adhered platelets on luminal surface of veins
      incubated or perfused with Defibrotide compared to veins treated with platelet
      rich plasma only revealed that Defibrotide has anti-thrombotic effects. TEM
      examination of ruthenium red (RR) stained thin sections of veins demonstrated
      that perfusion disrupts the glycosaminoglcan (GAG) coat on endothelial cells. But
      the presence of D in the perfusate preserves the integrity of GAG, indicating
      further cytoprotective effects of the drug on endothelium.

PMID- 10963785
TI  - Incorporation of an Asp-Ser sequence to form an RGDS-like motif in hirutonin: the
      effect on in vitro platelet function.
AB  - We investigated the effect on in vitro platelet function of hirutonin, a modified
      hirutonin with an RGD-like motif, a pseudo-RGDS peptide and a linear RGDS
      peptide. Inhibition of expression of surface fibrinogen on ADP-activated
      platelets with 40 microM of the peptide was as follows: hirutonin 10+/-3%,
      modified chimeric peptide 26+/-5%, pseudo-RGDS 66+/-11% and linear RGDS 93+/-13%.
      Both hirutonin and the chimeric peptide significantly inhibited ADP-induced
      platelet activation as detected by CD62 expression. Unlike the RGDS and pseudo
      RGDS controls, neither the chimeric peptide nor the parent hirutonin inhibited
      ADP-induced platelet aggregation even at 140 microM. The chimeric hirutonin
      peptide reduced ATP release from ADP-stimulated platelets by 40+/-4%. This
      inhibition was stronger than that caused by hirutonin (23+/-13%), but less than
      the RGDS (90+/-2%) and pseudo RGDS-peptides (59+/-11%). Primary platelet
      haemostasis was slightly but not significantly affected by the peptide at 40 and
      80 microM. However, shear-induced platelet adhesion to vWF and especially
      subsequent aggregate formation was interrupted after the addition of the chimeric
      peptide. Similar results were obtained with hirutonin. This inhibition was not as
      marked as with the RGDS- and pseudo-RGDS peptides. Both the parent hirutonin and
      the chimeric peptide caused prolongation of the clinical coagulation assays aPTT
      and TT. In conclusion, the chimeric hirutonin peptide with introduction of the
      RGD motif retained its anticoagulant effect but had little formal disintegrin
      activity. Instead, it appeared to have novel anti-platelet effects that may be of
      therapeutic use.

PMID- 10963787
TI  - Action of metalloproteinases mutalysin I and II on several components of the
      hemostatic and fibrinolytic systems.
AB  - The zinc endopeptidases mutalysin I (100 kDa) and mutalysin II (22.5 kDa) have
      been previously isolated from bushmaster (Lachesis muta muta) snake venom.
      Hemorrhagic activity was observed with as little as 0.5 microg (2000 units/mg)
      and 17.8 microg (56.2 units/mg) for mutalysin I and II, respectively.
      Additionally, the proteases hydrolyse the Aalpha>Bbeta chain of fibrinogen
      without clot formation. The specific fibrinogenolytic activity was estimated as
      5. 25 and 16.3 micromol fibrinogen/min/micromol protein for mutalysin I and II,
      respectively. In vitro, the enzymes act directly on fibrin and are not inhibited
      by serine proteinase inhibitors (SERPINS). Analysis by SDS-PAGE of fibrin
      hydrolysis by both enzymes showed that mutalysin II (0.22 microM) completely
      digested the alpha- and gamma-gamma chains and partially the beta-chain (in 120
      min incubation). In contrast, mutalysin I (three fold higher concentration than
      mutalysin II) hydrolyzed selectively the alpha-chain of fibrin leaving the beta
      and gamma-gamma chains unaffected. Unlike with the plasminogen activator-based
      thrombolytic agents (e.g., streptokinase), mutalysins do not activate
      plasminogen. Neither enzyme had an effect on protein C activation. Mutalysin II
      does not inhibit platelet aggregation in human PRP induced by collagen or ADP.
      However, mutalysin I showed a selective inhibitory effect on collagen-induced
      aggregation of human PRP; it did not affect platelet aggregation with ADP as the
      agonist. The present investigation demonstrates that both native and EDTA
      inactivated mutalysin I dose dependently blocked aggregation of human PRP
      elicited by 10 microg/mL of collagen with an IC(50) of 180 and 580 nM,
      respectively. These studies suggest that, in addition to the metalloprotease
      region of mutalysin I, the disintegrin-like domain also participates in the
      inhibitory effect. The proteolytic activity of mutalysin II against
      dimethylcasein and fibrin was completely abolished by alpha2-macroglobulin
      (alpha2-M). The stoichiometry of inhibition was 1.0 mol of enzyme per mol of
      alpha2-M. In contrast, the proteolytic effect of mutalysin I against the same
      substrates was not significantly inhibited by alpha2-M. Therefore, the data
      explain why mutalysin I contributes significantly not only to local but also to
      systemic bleeding associated with the observed pathological effects of the venom.

PMID- 10963786
TI  - Testing of platelet deposition on polystyrene surface under flow conditions by
      the cone and plate(let) analyzer: role of platelet activation, fibrinogen and von
      Willebrand factor.
AB  - Recently, we described a method of testing platelet deposition on extracellular
      matrix under flow conditions. The method was used for assessment of platelet
      function in various platelet disorders, for monitoring of replacement and anti
      platelet therapy. In the present study, we investigated platelet deposition on a
      polystyrene surface compared with that on extracellular matrix, under defined
      shear rates, using the original Cone and Plate(let) Analyzer. A correlation of
      adhesion rate (surface coverage) and aggregate formation (average size) of
      platelets from normal citrated blood between polystyrene and extracellular matrix
      was observed. Blocking of von Willebrand factor binding to glycoprotein Ib by a
      recombinant von Willebrand factor fragment substantially decreased platelet
      adhesion to both surfaces. Blocking of GPIIb-IIIa by Arg-Gly-Asp-Ser peptide
      prevented platelet adhesion to the polystyrene while an extensive adhesion of
      single platelets to extracellular matrix was observed. Furthermore, platelet
      adhesion to polystyrene but not to extracellular matrix was completely inhibited
      by platelet inactivation with prostaglandin E(1). Platelets from patients with
      severe von Willebrand disease yielded very low adhesion to both polystyrene and
      extracellular matrix. The addition of von Willebrand factor to the blood of these
      patients or pre-coating of polystyrene surface with von Willebrand factor
      restored the ability of platelets to adhere and aggregate on the surface.
      Platelets from patients with Glanzmann's thrombasthenia and afibrinogenemia
      adhered to extracellular matrix (with defective aggregate formation), while they
      failed to adhere to the polystyrene. Fibrinogen added to afibrinogenemia blood or
      pre-coating of the polystyrene with fibrinogen restored the ability of platelets
      to adhere and aggregate on the surface. In conclusion, the polystyrene surface,
      like extracellular matrix, can be used to assess platelet function disorders
      taking in account that platelet deposition on polystyrene under flow is
      absolutely dependent on platelet activation and on the presence of fibrinogen,
      von Willebrand factor, and their receptors.

PMID- 10963789
TI  - Purification and cDNA cloning of salmorin that inhibits fibrinogen clotting.
AB  - A new protein, salmorin, that inhibits fibrinogen clotting was purified to
      homogeneity from the snake venom of Agkistrodon halys brevicaudus. Salmorin was
      characterized to be a heterodimeric protein composed of 15 kDa and 14 kDa
      subunits. Purified salmorin inhibited not only thrombin-induced fibrinogen
      clotting but also factor Xa-induced prothrombin activation. Experimental evidence
      indicated that the hetero-dimeric protein does not bind to the thrombin catalytic
      site but binds to thrombin and prothrombin exosites. Analyses of the cDNA
      sequences encoding the two separate polypeptide chains revealed that the mature
      subunits are composed of 131 and 122 amino acids, respectively. In the isolated
      cDNAs, N-termini of both chains are preceded by hydrophobic signal peptides of 23
      residues. The deduced amino acid sequence exhibited considerable identity with
      other snake venom C-type lectin-like proteins derived from various snake venoms.

PMID- 10963788
TI  - Characterization of the anticoagulant actions of a semisynthetic curdlan sulfate.
AB  - Sulfation of curdlan, a natural, linear beta-1,3-glucan results in potent
      anticoagulant and antithrombotic agents. The different activity characteristics
      in the classical coagulation assays were shown to depend on various structural
      parameters. To obtain more detailed information about their structure-dependent
      mechanisms of action, one representative of these beta-1,3-glucan sulfates
      (CurS), was further investigated using several coagulation assays and amidolytic
      tests with chromogenic substrates. The mode of action of CurS differs from that
      of heparin. CurS reduces the thrombin formation by principally inhibiting the
      intrinsic FXa generation. As shown by amidolytic assays, it eliminates already
      generated thrombin mainly by accelerating the HCII-mediated thrombin
      inactivation, whereas its AT-mediated anti-thrombin activity is considerably
      lower than that of heparin. Further, it prevents the thrombin-mediated fibrin
      polymerization by directly interfering with the thrombin action on fibrinogen as
      well as by binding to fibrinogen. Finally, CurS is capable to activate the
      contact system with the consequence of a potential fibrinolytic effect. In
      conclusion, beta-1,3-glucan sulfates do not inhibit the blood coagulation
      nonspecifically due to their anionic character, but in dependence on their
      individual structure, they interfere specifically with the coagulation process at
      several sites.

PMID- 10963790
TI  - alpha(2)-plasmin inhibitor is a substrate for tissue transglutaminase: an in
      vitro study.

PMID- 10963791
TI  - Mutation of any site of N-linked glycosylation accelerates the in vivo clearance
      of recombinant rabbit antithrombin.
AB  - Antithrombin (AT) is a plasma protein with four sites of N-linked glycosylation.
      Asn 135 is incompletely glycosylated, and the resulting 3-glycan AT is cleared
      more rapidly in vivo than the 4-glycan form. The Asn codons in each of the four
      sites of glycosylation were altered in turn, to create four mutant rabbit AT
      cDNAs. Permanently transfected CHO cell lines were generated following
      transfection of the resulting constructs, encoding either the wild-type rabbit AT
      (AT-WT) or one of the four underglycosylated variants (AT-N96Q, AT-N135Q, AT
      N155Q, and AT-N155Q). Comparison of the five resulting recombinant AT proteins
      revealed that the major AT species of each variant co-migrated on SDS gels, and
      migrated more rapidly than the major form of AT-WT. The shift in mobility, from
      60 to 57 kDa, was consistent with the loss of one fully sialylated complex N
      linked glycan. Neither the amount of AT secreted (range: 1.25 to 4.2 microg/10(6)
      cells/day) nor the kinetics of secretion differed significantly between cell
      lines expressing AT-WT or any of the AT variants. All forms of recombinant rabbit
      AT were capable of forming denaturation-resistant complexes with thrombin.
      Purification and radioiodination of each of the five recombinant AT proteins
      permitted pharmacokinetic analysis of their individual clearance in rabbits.
      While neither the equilibration half-life (t(0.5)alpha) nor the terminal
      catabolic half-life (t(0. 5)beta) differed significantly between plasma-derived
      rabbit AT and AT-WT, the t(0.5)beta of all the underglycosylated variants was
      decreased relative to that of AT-WT (maximum reduction in mean: from 70.1+/-3.2 h
      to 52.4+/-2.5 h). These results suggest that the overall extent of glycosylation,
      rather than the location within AT of the glycan chains, is a primary determinant
      of AT clearance.

PMID- 10963792
TI  - Tyrosyl radicals in prostaglandin H synthase-1 and -2.

PMID- 10963793
TI  - Structural basis for the positional specificity of lipoxygenases.
AB  - The positional specificity of arachidonic acid oxygenation is currently the
      decisive parameter for classification of mammalian lipoxygenases but,
      unfortunately, the structural reasons for lipoxygenase specificity are not well
      understood. Although there are no direct structural data on
      lipoxygenase/substrate interaction, experiments with modified fatty acid
      substrates and mutagenesis studies suggest that for 12- and 15-lipoxygenases,
      arachidonic acid slides into the substrate-binding pocket with its methyl end
      ahead. For arachidonate 5- and/or 8-lipoxygenation two alternative models for the
      enzyme/substrate interaction have been developed: 1) The orientation-determined
      model and 2) the space-determined model. This review explores the experimental
      data available on the mechanistic reasons for lipoxygenase specificity and
      concludes that each of the above-mentioned hypotheses may be valid for
      arachidonate 5-lipoxygenation under certain circumstances.

PMID- 10963794
TI  - Biochemical and molecular characteristics of the cytochrome P450 arachidonic acid
      monooxygenase.

PMID- 10963795
TI  - Growth hormone response to clonidine in adversely reared young adult primates:
      relationship to serial cerebrospinal fluid corticotropin-releasing factor
      concentrations.
AB  - A reduction of the growth hormone (GH) response to the alpha(2) adrenergic
      agonist clonidine is a neuroendocrine abnormality observed with reasonable
      consistency among human patients with mood and anxiety disorders. In previous
      primate studies, in comparison to predictably reared controls, monkeys exposed as
      infants to maternal variable foraging demand (VFD) rearing exhibited persistent
      elevations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), as
      well as other biological disturbances. As CRF has been demonstrated to inhibit GH
      release, the authors hypothesized that within VFD-reared subjects, animals with
      relatively high CRF concentrations would exhibit relatively diminished GH
      responses to clonidine. The current study examined the relationship between the
      GH response to clonidine in VFD-reared adult primates in relation to a range of
      both juvenile and follow-up CSF CRF concentrations. Nine bonnet macaques (Macaca
      radiata) were given ascending dosages of clonidine under ketamine anesthesia.
      Plasma samples for GH-like immunoreactivity were obtained throughout the session.
      A significant positive correlation was noted between juvenile CSF CRF
      concentrations and the levels of the neuropeptide observed in young adults. The
      mean of the serial CSF CRF concentrations exhibited a significant inverse
      relationship towards the GH response to clonidine in young adulthood, with
      relatively high CSF CRF associated with relatively attenuated GH responses to
      clonidine. These data raise the possibility that a reduced GH response to
      clonidine may inversely reflect trait-like increases of central nervous system
      (CNS) CRF activity.

PMID- 10963796
TI  - Low serum cholesterol in violent but not in non-violent suicide attempters.
AB  - Many previous studies have suggested that low or lowered serum cholesterol levels
      may increase the risk of mortality not due to somatic disease: principally,
      suicide and violent death. Because violent death is rare, some studies have
      investigated afterwards the relation between cholesterol levels and either
      suicide attempts in psychiatric populations or violence in criminally violent
      populations. However, none of these studies have compared cholesterol levels in
      violent and non-violent suicide attempters. The blood of 25 consecutive drug-free
      patients following a violent suicide attempt and of 27 patients following a non
      violent suicide attempt by drug overdose was drawn in the 24 h following
      admission. Patients with a diagnosis of alcohol abuse and with cholesterol
      lowering therapy were excluded. Age, sex, body mass index, psychiatric diagnosis
      and the physical conditions of the suicide attempt were investigated. Thirty-two
      healthy subjects were used as a control group. There were no differences between
      the groups in age, frequency of psychiatric diagnoses or body mass index. There
      was more women in the group of non-violent suicide attempters than in that of
      violent suicide attempters (P<0.001). In analyses controlling for sex and age,
      the serum cholesterol concentration was 30% lower (F(2,82)=15.8; P<0.0001) in the
      group of violent suicide attempters (147+/-54 mg/dl) than in the group of non
      violent suicide attempters (209+/-38 mg/dl) or control subjects (213+/-46 mg/dl).
      Our results showed that low serum cholesterol level is associated with the
      violence of the suicide attempt and not with the suicide attempt itself. Further
      investigations are necessary to determine the usefulness of this easily
      accessible parameter as a potential risk indicator for violent acts such as
      violent suicidal behavior in susceptible individuals.

PMID- 10963798
TI  - Positive symptomatology and source-monitoring failure in schizophrenia--an
      analysis of symptom-specific effects.
AB  - Recent research has suggested that certain positive symptoms in patients with
      schizophrenia are linked to self monitoring/reality-monitoring deficits. We
      wished to investigate the association between such deficits and three specific
      symptoms: hallucinations, delusions and thought disorganisation. Forty patients
      with schizophrenia and 40 normal controls were administered a source-monitoring
      task. Twenty-four items were produced, either verbally by the experimenter, or
      verbally by the subject, or presented as pictures. Then, subjects were read a
      recognition list including the produced target items mixed with distractors. They
      were required to recognise the target items and to remember their source of
      production. The pattern of memory deficits has previously been reported (Brebion,
      G., Smith, M., Gorman, J., Amador, X., 1997. Discrimination accuracy and decision
      biases in different types of reality monitoring in schizophrenia. Journal of
      Nervous and Mental Disease 185, 247-253). The current analyses focussed on the
      false recognition of distractors, and on the errors in the source attribution of
      the recognised target items. Results showed that higher hallucination scores were
      associated with an increased tendency towards false recognition of non-produced
      items. In addition, hallucinators were more prone than control subjects to
      misattribute to another source the items they had produced themselves.
      Furthermore, hallucinators and delusional patients were more prone than the other
      patients to report that spoken items had been presented as pictures. This latter
      finding suggests that both hallucinations and delusions are associated with
      confusion between imagined and perceived pictures. Our previous report stated
      that only one of the three investigated types of response bias was associated
      with global positive symptomatology. However, this finer-grained analysis
      revealed that the three of them were in fact associated with hallucinations
      and/or delusions. On the other hand, thought disorganisation appeared to be
      independent from these mechanisms.

PMID- 10963799
TI  - Semantic verbal fluency deficit as a familial trait marker in schizophrenia.
AB  - This study examined neurocognitive deficits as familial vulnerability factors to
      schizophrenia. Twenty-three Chinese schizophrenic patients, 21 of their non
      psychotic siblings and 26 healthy volunteers, matched for age, sex and education,
      were assessed by using a battery of neurocognitive tests including: Wisconsin
      Card Sorting Test (WCST), semantic verbal fluency, logical memory, digit span,
      information, comprehension and similarity. The results showed that siblings had
      significantly less word output in the verbal fluency test as compared to
      controls. No significant difference was found between siblings and controls for
      other tests except that a trend difference was noted for the performance on the
      similarity test and number of categories completed on the WCST. The verbal
      fluency abnormality can be considered as a familial trait marker for
      schizophrenia. Relationships between the residual symptoms after an acute
      psychotic episode and the magnitude of familial risk were examined. More severe
      residual symptoms of probands at clinical remission could be predicted by their
      older age of onset and by better verbal fluency performance in their non
      psychotic siblings. This tentatively suggests that patients with a milder genetic
      form of schizophrenic illness may have a more severe environmental contribution
      to cerebral insult according to the multifactorial/threshold model. The
      environmental cerebral insult may cause structural abnormalities leading to
      incomplete remission of clinical symptoms.

PMID- 10963797
TI  - Concurrent measures of protein kinase C and phosphoinositides in lithium-treated
      bipolar patients and healthy individuals: a preliminary study.
AB  - This study examined the hypothesis that lithium inhibits the PI signaling pathway
      in humans during in vivo administration by concurrently measuring PKC isozymes
      and platelet membrane phosphoinositides in lithium-treated patients and healthy
      individuals. The platelet membrane and cytosolic levels of PKC alpha, beta I,
      beta II, delta, and epsilon were measured using Western blotting. The relative
      platelet membrane contents of phosphatidylinositol (PI), phosphatidylinositol-4
      phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP(2)) were measured
      with two-dimensional thin-layer chromatography. Nine euthymic lithium-treated
      bipolar subjects and 11 healthy control subjects were studied. Compared to
      control subjects, lithium-treated bipolar patients had significantly lower levels
      of cytosolic PKC alpha isozyme (t-test=-3.24, d.f.=17, P=0.01) and PIP(2)
      platelet membrane levels (t-test=-2.51, d.f.=18, P=0.02), and a trend toward
      reduced levels of cytosolic PKC beta II isozyme (t=-2.17, d.f.=17, P=0.05). There
      was no significant correlation between PIP(2) and any of the PKC isozymes. These
      preliminary findings suggest that chronic lithium treatment may decrease the
      levels of both cytosolic PKC alpha isozyme and membrane PIP(2) in platelets of
      bipolar disorder patients.

PMID- 10963800
TI  - Symptom provocation alters behavioral ratings and brain electrical activity in
      obsessive-compulsive disorder: a preliminary study.
AB  - Regional brain activity was measured using quantitative electroencephalography
      (EEG) in six patients with obsessive-compulsive disorder (OCD) during live and
      imaginal exposure to feared contaminants. OCD symptoms increased significantly
      from baseline levels during live and imaginal exposures. However, live exposure
      provoked significantly more OCD symptoms than imaginal exposure. There was a
      significant change in the anterior-to-posterior scalp distribution of alpha power
      during live exposure. These preliminary results suggest that: (1) live exposure
      is more effective than imaginal exposure in altering behavioral and
      electrophysiological measures; and (2) live exposure is associated with regional
      EEG changes in OCD.

PMID- 10963801
TI  - Reduced facial expression and social context in major depression: discrepancies
      between facial muscle activity and self-reported emotion.
AB  - The expression of emotion is determined by emotion and the presence and absence
      of others, i.e. social context. The present study examined social context
      differences in facial muscle activity and self-reported emotion of 11 major
      depressed and 11 non-depressed patients. Subjects were asked to imagine happy and
      sad situations with and without visualizing other people. Facial muscle activity
      over the brow and cheek region was reduced in depressed compared to non-depressed
      patients during happy and sad imagery whereas self-reported emotion showed no
      group differences. In both subject groups, happy imagery induced increased
      smiling and self-reported happiness whereas sad imagery induced increased
      frowning and self-reported sadness. Smiling and self-reported happiness were
      increased during happy-social compared to happy-solitary imagery in both groups.
      In contrast, frowning showed a lack of social context differences, although self
      reported sadness was increased during sad-social vs. sad-solitary imagery in both
      groups. Reduced facial muscle activity in depression may indicate psychomotor
      retardation whereas the lack of social context differences in frowning may
      suggest social disengagement and an inhibition of sad facial expression in the
      presence of others.

PMID- 10963802
TI  - Reliability and validity studies of the Facial Discrimination Task for emotion
      research.
AB  - The Facial Discrimination Task (FDT) (Erwin, R.J., Gur, R.C., Gur, R. E.,
      Skolnick, B., Mawhinney-Hee, M., Smailis, J., 1992. Facial emotion
      discrimination: I. Task construction and behavioural findings in normal
      participants. Psychiatry Research 42, 231-240.) consists of standardized black
      and-white photographs of Caucasian actors exhibiting happy, sad, and neutral
      faces. Originally designed for brain-imaging research in emotion recognition in
      schizophrenia and major depression, it has since been successfully employed in
      emotion recognition studies on mental retardation and psychosomatic disorders.
      This article presents new basic psychometric data from three studies with a total
      of 401 college undergraduates. Content validity, item reliability (test-retest,
      item-total correlation, item difficulty) and test reliability (internal
      consistency) were established. Happy and sad items were easier to agree upon than
      neutral ones. In general, happy items had the highest validity, highest test
      retest reliability, and highest item-total correlations. Recognition errors of
      neutral items were biased toward negative affect. Advantages and limitations of
      the FDT for clinical research applications are discussed.

PMID- 10963803
TI  - Enhancement of the immune response to hepatitis B virus vaccine by antigen
      specific IgM.
AB  - In the present study, modulation of antibody response induced by Hepatitis B
      virus vaccine-IgM complex was investigated. Purified IgM-type anti HBv monoclonal
      antibody (1B11) was complexed to commercially available HBv vaccine (GenHevac B
      Pasteur, France) at varying concentrations of HBsAg (0.5, 1, 1.5 microg of HBsAg)
      and used to immunize BALB/c mice. An enhanced humoral immune response was
      obtained with the HBv vaccine-IgM complex at all the doses compared with those
      immunized by vaccine alone and increased antibody levels were observed with
      increased concentrations of HBsAg in vaccine formulation. Immunization with HBv
      vaccine-IgM complex mostly generated IgG-type antibodies in the sera of mice, and
      also gave rise to the development of hybrid cells which predominantly produced
      IgG-type monoclonal antibodies. Hence, results from this study indicate that 1B11
      can be effectively used to obtain a better immune response to HBv vaccine.

PMID- 10963804
TI  - Telomerase activity of peripheral blood lymphocytes in patients with chronic
      hepatitis B.
AB  - Chronic hepatitis B is the immunocompromising condition. The decrease of
      lymphocyte telomerase is linked to immunosenescence in hosts. To know whether
      telomerase activity of lymphocytes is involved in immunopathogenesis in patients
      with chronic hepatitis B, telomerase activity of peripheral lymphocytes was
      determined in such patients. The results showed that telomerase activity in
      resting peripheral lymphocytes of healthy subjects was detectable at low level,
      and obviously increased (P<0.001) after stimulation in vitro with
      phytohaemagglutinin (PHA). Telomerase activity of lymphocytes decreased with age
      in both groups with or without PHA stimulation. Telomerase activity of resting
      lymphocytes in patients with chronic hepatitis B was also observed at detectable
      level and markedly upregulated after PHA stimulation. The decreased telomerase
      activity of resting lymphocytes was found in patients with chronic hepatitis B
      (n=14, 0.32+/-0.27) compared to that in healthy subjects (n=17, 0. 52+/-0.28;
      P<0.05). However, there was no difference present between these two groups in
      telomerase activity of activated lymphocytes with PHA. In addition, no effect of
      recombinant human interleukin-12 (rhIL-12) on telomerase expression was observed
      in either the patient group or the healthy group. We concluded that the decreased
      telomerase activity of lymphocytes in chronic hepatitis B patients is present,
      which may be partly responsible for immunosuppressive condition in such patients.

PMID- 10963805
TI  - Beyond danger: unmethylated CpG dinucleotides and the immunopathogenesis of
      disease.
AB  - Oligonucleotide sequences containing unmethylated cytidine phosphate guanosine
      (CpG) motifs are known to have significant immunostimulatory properties. Because
      of these immunostimulatory effects, unmethylated CpG oligonucleotides are thought
      to act as 'danger signals' that produce a favorable immune response by alerting
      the host to the presence of invading organisms or abnormal cells. In contrast to
      this concept, we review the evidence that unmethylated CpG sequences derived
      either from microbial agents or from endogenous CpG-rich Alu motifs promote
      disease progression by inducing an aberrant or autoreactive immune response.
      Recognition of the negative effect of unmethylated CpG dinucleotides should lead
      to more effective immune strategies to combat infectious, inflammatory,
      autoimmune and malignant diseases.

PMID- 10963806
TI  - Human interferon-beta inhibits binding of HIV-1 gp41 to lymphocyte and monocyte
      cells and binds the potential receptor protein P50 for HIV-1 gp41.
AB  - Previous findings have indicated that HIV-1 gp41 like human type I interferon
      (IFN) could inhibit lymphocyte proliferation and up-modulate MHC class I, II and
      ICAM-1 molecule expression, and a common epitope exists between gp41 and type I
      interferon (IFN-alpha and -beta) in the receptor binding regions. To clarify the
      relationship between human type I interferon and HIV-1 gp41, we tried to inhibit
      recombinant soluble gp41-binding to human T, B and monocyte cell lines by human
      IFN-alpha, -beta and -gamma. It was interestingly observed that IFN-beta after
      preincubating with cells could inhibit the binding of rsgp41 to H9, Raji and U937
      cells (T, B and monocyte cell lines), while this binding could not be inhibited
      by another type I interferon (IFN-alpha) and a type II interferon (IFN-gamma). It
      was further examined whether human IFN-alpha and -beta bind to the gp41 binding
      protein P50. In ELISA-assay, the human IFN-beta, but not IFN-alpha, could bind to
      P50 which was identified as a potential cellular receptor protein for gp41
      binding. By the affinity capillary electrophoresis (ACE) analysis, formation of
      stable IFN-beta-P50 complex was observed. These results indicate that IFN-beta
      binds the potential receptor protein P50. Based on these experimental evidences
      and previous studies, it was presumed that the potential cellular receptor
      protein P50 may be the 51 kDa subunit of human IFN-alpha/beta receptor, which
      needs to be verified in the future.

PMID- 10963807
TI  - Anti-endothelial cell antibodies in patients with coronary atherosclerosis.
AB  - Anti-endothelial cell antibodies (AECA) have been shown to possess endothelial
      cell activation properties and to harbor pathogenic potential in experimental
      animal models of autoimmune systemic disorders. Atherosclerosis is a form of an
      inflammatory condition in which the immune system has been shown to be involved.
      The aim of the present study was to assess the presence of AECA in patients with
      coronary atherosclerosis. A total of 134 patients admitted for chest pain of
      suspected anginal origin were evaluated for coronary artery atherosclerosis by
      angiography. Sera were drawn prior to the procedure for the determination of AECA
      employing cyto-ELISA. AECA positive sera were further evaluated for its ability
      to promote in vitro E-selectin expression by HUVEC using a cell-based ELISA.
      Patients with no coronary artery involvement had levels of AECA that did not
      differ from those obtained for patients with confirmed coronary atherosclerosis
      (one, two or three vessel disease). Furthermore, AECA positive sera from
      patients, with or without coronary atherosclerosis displayed similar capacity of
      inducing E-selectin expression by endothelial cells. AECA may not stand as an
      optimal mean of discriminating atherosclerotic from non-atherosclerotic patients.
      The ability of AECA to activate endothelial cells is also not unique to patients
      with atherosclerosis and is evident also in age-matched control subjects.

PMID- 10963808
TI  - Anti-DNA antibodies exhibit different binding motif preferences for single
      stranded or double stranded DNA.
AB  - A common feature for most anti-DNA antibodies (Abs) is their induction in an
      antigen (Ag)-driven specific clonal expansion pattern though crossreactivity.
      However, the fine sequences in DNA Ags that interact directly with immune system
      and the ability of DNA to induce immune responses is poorly understood. In order
      to define the characteristics of possible antigenic determinants in DNA Ags, we
      immunized mice with the pBR322 plasmid and used antisera as source of anti-DNA
      Abs. A systemic evolution of ligands by exponential enrichment (SELEX) procedure
      was performed on an oligodeoxynucleotide library either in single stranded (ss-)
      or double stranded (ds-) form. The SELEXed fragments were cloned and sequenced.
      The resulting sequences were analyzed using the Multiple Alignment Construction
      and Analysis Workbench program. We show that the fragments of ss- or ds- form
      bound by a same stock of antibodies were different in their conserved sequences.
      ss-DNA fragments recognized by anti-DNA Abs were rich in cacc, caccc, accc or
      cccc blocks, while the same stock of Abs exhibited significant preference for the
      (5'gcg3'/3'cgc5') motif located in ds-DNA. At the same time sera from unimmunized
      control mice showed no sequence preference in either ss-DNA or ds-DNA. Future
      improvement of this work and the potential use of SELEX for studies of DNA Ags
      are also discussed.

PMID- 10963809
TI  - Absence of interleukin-4 enhances germinal center reaction in secondary immune
      response.
AB  - The germinal center (GC) is a compartment for B cell differentiation and
      proliferation. Interleukin (IL)-4 has been considered essential for GC
      functioning. To define the role of IL-4 in GC reaction, immunohistology of
      draining lymph nodes (LNs) of IL-4 gene-targeted (IL-4(-/-)) mice was performed
      during secondary immune response. IL-4(-/-) mice were immunized with ovalbumin
      emulsified in Freund' complete adjuvant. Final antigen challenge was done 4 weeks
      later. IL-4(-/-) mice had a higher production of IgG2a and IgG2b and a lower
      production of IgG1 than those in wild-type (WT) mice. In comparison with WT mice,
      LNs of IL-4(-/-) mice on days 4 and 7 after final antigen challenge were larger
      and contained a markedly greater number of GCs, which showed marked size
      variations with a large number of small GCs and a small number of markedly large
      GCs. By day 14, the number of GCs decreased to the same level as that in WT mice.
      However, the LN size in IL-4(-/-) mice was still larger than that in WT mice due
      to the presence of markedly large GCs. Although well-developed complement
      receptor(+) follicular dendritic cell (FDC) networks were present in GCs of IL-4(
      /-) mice, no FDCs of mature phenotype (CD23(+)) were observed in many of the
      small GCs. In conclusion, the absence of IL-4 enhanced GC reaction and specific
      antibody response of Th1-type. IL-4 may play an important role in inducing the
      appropriate magnitude of humoral immune response.

PMID- 10963810
TI  - CD4 Th1 but not Th2 clones efficiently activate macrophages to eliminate
      Trypanosoma cruzi through a nitric oxide dependent mechanism.
AB  - We have recently generated CD4 clones from BALB/c mice immunized with a plasmid
      DNA containing the gene encoding for the catalytic domain of trans-sialidase, an
      important enzyme expressed on the surface of Trypanosoma cruzi trypomastigotes.
      These clones allowed us to study in vitro the interaction between T cells and T.
      cruzi-infected macrophages. A cytotoxic CD4 clone of the Th1 type effectively
      activated macrophages to kill intracellular amastigote forms of T. cruzi. In
      contrast, CD4 Th2-like clones were much less efficient, being unable to activate
      macrophages to significantly reduce parasite development. We found that the anti
      parasitic activity of Th1 cells was completely suppressed by the presence of
      nitric oxide synthase inhibitors. Also, we observed that anti-IFN-gamma
      antibodies significantly inhibited the anti-parasitic activity of these cells. We
      conclude that trypomastigote-specific Th1 cells activate macrophages to kill
      intracellular amastigotes of T. cruzi by a mechanism exclusively dependent on the
      induction of nitric oxide synthesis.

PMID- 10963811
TI  - Cytokine production by peripheral blood mononuclear cells following birch-pollen
      immunotherapy.
AB  - We studied the Th2/Th1 balance by short-term stimulation of peripheral blood
      mononuclear cells (PBMC) isolated during the pollen season from seven allergic
      patients treated with conventional birch-pollen immunotherapy (IT) for 18 months,
      eight matched allergic control patients and 10 non-atopic individuals. The PBMC
      were cultured for 7 days with birch-pollen extract (BPE) or tetanus toxoid (TT),
      and then restimulated with PHA and PMA to induce high IL-5, IL-10 and IFN-gamma
      production. The serum levels of birch-pollen-specific IgG and IgG4 were
      significantly elevated after IT treatment. The proliferative response to BPE was
      significantly enhanced in the allergic control group, but not in the IT-treated
      group, compared to the non-atopic group (P<0.05). Birch-pollen-specific IL-5
      production was significantly enhanced in both the IT-treated group and the
      allergic control group (P<0.01-0. 05). Furthermore, both the IT-treated group and
      the allergic control group had a cytokine profile to BPE significantly more Th2
      polarized (high IL-5/IFN-gamma ratio) than to TT (P<0.05 and P<0.01,
      respectively). No differences in IL-10 production between the three study groups
      were observed. The Th2/Th1 balance in vitro correlated with the serum
      concentrations of birch-pollen-specific IgE (r=0.60, P<0.05), and in the IT
      treated group, also with the IgG and IgG4 levels (r=0.79, P<0.05 and r=0.86,
      P<0.05, respectively). We conclude that conventional birch-pollen IT does not
      lead to changes in the cytokine profile of the circulating pool of allergen
      specific T cells during birch-pollen season. However, induction of peripheral T
      cell tolerance and increased production of specific IgG and IgG4 might be part of
      the mechanisms of IT.

PMID- 10963812
TI  - Pulmonary function changes and increased Th-2 cytokine expression and nuclear
      factor kB activation in the lung after sensitization and allergen challenge in
      brown Norway rats.
AB  - BACKGROUND: Our purpose was to evaluate the expression of Th-1 and Th-2 related
      cytokine mRNA and nuclear factor (NF) kB in the lung tissue of ovalbumin (OA)
      sensitized brown Norway rats (BNR). We also evaluated the correlation between
      bronchial hyperreactivity (BHR) and eosinophils with cytokine mRNA expression.
      METHODS: Eight BNR (weight range 250-350 g) were sensitized by inhaled OA (group
      I) with a 1-week interval between and then provoked with OA 1 week later.
      Pulmonary function tests (PFT) were performed at baseline and 24 h after
      acetylcholine challenge. Eight weight-matched normal BNR served as controls
      (group II). All animals were anesthetized, paralyzed with gallamine, and
      ventilated via tracheostomy. They were given varying doses of acetylcholine (25,
      50, 75, 100 microg/kg) injected through a jugular venous catheter. Five seconds
      after acetylcholine injections, PFTs were performed, including a maximal forced
      expiratory maneuver (MFEM), airway opening pressure (P(ao)) at tidal breathing
      and total dynamic lung compliance (C(dyn)). Bronchoalveolar lavage (BAL) was then
      performed with 20 ml normal saline divided into two doses. Thereafter, the lungs
      were removed and examined histologically. Total RNA was extracted from lung
      tissue samples and reverse-transcriptase polymerase chain reaction was performed
      using primers for mRNA of IL-4, IL-5, IL-10, interferon-gamma (IFNr) and beta
      actine. RESULTS: Group I OA treated rats had typical airway obstruction on PFTs
      and airway inflammation on histological examination. Ratios of IL-4, IL-5, IL-10
      and inducible nitric oxide synthase (iNOS) mRNA levels to beta-actine as measured
      by densitometry were significantly lower in controls than in OA-sensitized rats.
      The IFNr mRNA to beta-actin ratio was significantly reduced in OA-sensitized
      rats. Group I demonstrated a band shift when compared with group II in
      electromobility shift assay (EMSA) for NF-kB indicating increased activation of
      this transcription factor. CONCLUSION: Th-2 related cytokine mRNA was increased
      but Th-1 related cytokine mRNA was decreased in OA-sensitized BNR. An increased
      level of Th-2 related cytokine mRNA correlated with decreased airflow and
      inflammatory changes. These results demonstrate the value of the BNR model for
      studying allergic asthma at the molecular level.

PMID- 10963815
TI  - Preface.

PMID- 10963813
TI  - Induction of NK1.1(+) alpha beta TCR(+) T cells by bypassing TCR signals in ZAP
      70 deficient mice.
AB  - The mechanism of development of a unique subset of T cells, thymic NK1.1(+) alpha
      beta T cells, has been poorly understood. We found that the development of thymic
      NK1.1(+) alpha beta T cells was defective in mice deficient in ZAP-70. Instead,
      an accumulation of NK1.1(+) TCR beta(-) NK-like population was detected in the
      thymus and spleen of the ZAP-70 deficient (ZAP -/-) mouse. In the present report,
      we examined whether biochemical treatments that replace TCR-mediated positive
      selection signals could restore the generation of thymic NK1.1(+) alpha beta T
      cells in ZAP -/- mice using the thymus organ culture. We found that a higher
      concentration of phorbol ester (PMA) than that required for CD4(+) T cell
      generation and ionomycin induced the generation of NK1.1(+) alpha beta T cells.
      Phenotypic analysis of the induced NK1.1(+) alpha beta T cell population
      suggested that these cells expressed CD8 but not CD4 molecules, which is a
      different characteristic from ordinary thymic NK1.1(+) alpha beta T cells. These
      results suggest that differential signaling is required for the generation of
      mainstream T cells and thymic NK1.1(+) alpha beta T cells.

PMID- 10963814
TI  - Comparison of IgG preparations by a turbidimetric assay of opsonizing capacity.
AB  - A convenient turbidimetric phagocytosis assay was applied for the functional
      comparison of various intravenous IgG preparations. Staphylococcus aureus
      (Oxford) was opsonized by the immunoglobulin samples in the presence of an IgG
      deficient serum as a source of complement. The opsonized bacteria were subjected
      to phagocytosis by neutrophil granulocytes isolated from healthy adults. The time
      course of phagocytosis was monitored by the decrease of light absorbance at 400
      nm. Changes in light absorbance during a 15 min period of opsonophagocytosis
      (delta E(400)) were expressed as a percentage of delta E(400) obtained by a
      reference IgG preparation. The opsonizing effect of five commercially available
      i.v. IgG preparations was compared. Three different preparations containing
      whole, non-modified IgG molecules had a comparable opsonizing effect while a
      further one prepared by propiolacton modification displayed a reduced activity
      (52%) of the reference preparation, taken as 100%. A preparation consisting of
      IgG molecules without an Fc-region proved to be practically ineffective (8.7%).

PMID- 10963816
TI  - Editorial comment

PMID- 10963817
TI  - Survey of mRNAs encoding zinc transporters and other metal complexing proteins in
      pancreatic islets of rats from birth to adulthood: similar patterns in the
      Sprague-Dawley and Wistar BB strains.
AB  - The zinc content in the pancreatic beta cell is among the highest of the body,
      but information about which proteins might handle zinc in the beta cell is
      unknown. In the present work RT-PCR was used to obtain clues about the
      developmental expression of genes encoding metal complexing proteins in the
      pancreatic islets of the normal Sprague-Dawley rat and the BB diabetes resistant
      (BBDR) rat. The BBDR rat possesses beta cells genetically identical to the BB
      diabetes prone (BBDP) rat which exhibits an autoimmune diabetes quite similar to
      type 1 diabetes in humans, but in contrast to the BBDP rat, the islets of the
      BBDR rat are amenable to study because they are not destroyed by immune attack.
      There was no difference in the expression of any of the genes studied between the
      two strains of rats. mRNAs encoding zinc transport proteins ZnT-1 and ZnT-4, as
      well as calreticulin, ferritin heavy and light chains, metallothionein 1,
      metallothionein 3, Nramp1, Nramp2, transferrin, and the transferrin receptor were
      readily detected in pancreatic islets of 10-day-old, 5-week-old, and adult (60 to
      90-day-old) rats. In contrast to the islet, mRNAs encoding metallothionein 3,
      Nramp1, Nramp2, ZnT-2, ZnT-3, and ZnT-4 and transferrin were not detected in the
      whole pancreas of adult Sprague-Dawley rats. In the whole pancreas of 3-day-old
      rats, ZnT-1 was the only zinc transporter mRNA detected and its level was
      moderate. Moderate to high levels of mRNA encoding calreticulin and the light and
      heavy chains of ferritin, as well as transferrin and the transferrin receptor,
      were detected in whole pancreas at 3 days. ZnT-2 and ZnT-3 mRNAs were present in
      low to moderate levels in pancreatic islets of 10-day and 5-week-old rats, but
      were absent in 3-day-old pancreas and islets of adult animals. These results
      indicate that expression of these proteins is developmentally regulated in the
      islet. In both Sprague-Dawley and BB rats, high levels of mRNAs encoding known
      beta cell proteins as controls (cytochrome b558, quinone reductase, the
      tricarboxylic acid transport protein and the receptors for IGF-1 and IGF-2 and
      insulin) were present in islets from 10 days to adulthood. Levels of mRNAs
      encoding quinone reductase, the tricarboxylic acid transport protein cytochrome
      b558 and the receptors for IGF-2 and insulin, were low or absent in 3-day-old and
      adult pancreas. BB rats were studied in an attempt to discern a difference
      between normal rats and the BB strain of rats, because, perhaps, delayed
      expression of a beta cell protein results in failure of immune tolerance against
      the beta cell. According to this paradigm none of the proteins examined in the
      current study appear to be a candidate for initiating an immune response in the
      BB rat.

PMID- 10963818
TI  - Reliability of digital videometry and acetate tracing in measuring the surface
      area of cutaneous wounds.
AB  - PURPOSE: The purpose of this study was to evaluate the reliability of digital
      videometry and acetate tracing in the measurement of cutaneous wound area.
      METHODS: Four clinicians used both digital videometry and acetate tracing to
      measure five wounds that were artificially created on a cadaver specimen. In
      addition, the clinicians used an analog centimeter ruler to determine a rough
      estimate of the area of each wound. The wounds were measured a total of five
      times with each measurement instrument using a non-sequential repeat measures
      design. Associations between the three wound measurement techniques were examined
      with Pearson correlation coefficients. In addition, intraclass correlation
      coefficients (ICC) were calculated for each pair of the three measurement
      techniques. RESULTS: Correlation between the measurement systems for all raters
      combined yielded Pearson r-values of 0.93 for ruler and acetate, 0.95 for ruler
      and digital and 0.97 for acetate and digital. Furthermore, the average measure
      ICC between acetate and digital was 0.94, between acetate and ruler was 0.76 and
      between digital and ruler was 0.57. CONCLUSION: These results suggest that wound
      area measurements obtained using digital videometry and acetate tracing are very
      similar and both techniques can be used interchangeably in either clinical or
      research settings.

PMID- 10963819
TI  - Efficacy and safety of single versus multiple daily doses of glibenclamide in
      type 2 diabetes mellitus.
AB  - Although long acting, glibenclamide is frequently given in split doses for type 2
      diabetes mellitus. This may discourage compliance. It is thus appropriate to
      consider dosing it less frequently. We therefore studied glibenclamide effects
      when used once daily and when used in split doses. Our objective was to assess
      the feasibility of using once daily dosing as a regimen of choice. We measured
      plasma glucose, insulin, glibenclamide, lipids, HbAl and body mass index
      associated with the regimens. We also compared the number of hypoglycemic
      episodes occurring with them. Thirty type 2 diabetics on multiple daily
      glibenclamide were enrolled. Their regimens were changed over to once daily.
      Blood for glucose, insulin, lipids, HbAl and glibenclamide and body weight
      measurements were determined before and after the crossover period. We found no
      major difference in the sugar and insulin profiles with the two regimens. Fasting
      total cholesterol and triglyceride were also similar and so were plasma
      glibenclamide. The HbAl levels and body mass index and number of minor and major
      hypoglycemic episodes and hospital admissions for hypoglycemia also did not
      differ. We conclude that single daily dosing of glibenclamide was equivalent to
      multiple daily dose regimens. It can be used to an advantage to improve patient's
      compliance.

PMID- 10963820
TI  - A case of chronic hepatitis C developing insulin-dependent diabetes mellitus
      associated with various autoantibodies during interferon therapy.
AB  - We report a case of chronic hepatitis C presenting insulin-dependent diabetes
      mellitus (IDDM) associated with various autoantibodies including possible anti
      insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old
      man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis
      received IFN therapy. The thyroid function was well-controlled by administration
      of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks
      after starting IFN (reaching 530 million units of total dose), marked thirst
      happened, with increased fasting plasma glucose level (488 mg/dl) and decreased
      daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM
      occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA,
      and thyroid autoantibodies titers increased, but without pancreatic islet cell
      antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was
      stopped and insulin treatment was started, but plasma glucose level was not
      controlled well. AIRA became negative 2 months later, however, insulin antibody
      (IA) was positive when tested after 18 months. Serum HCV RNA has been negative,
      and a normal level of serum transaminase has been observed since IFN therapy. It
      is likely that IFN therapy induced the immunological disturbance and resulted in
      occurrence of various autoantibodies and IDDM in the patient.

PMID- 10963821
TI  - Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance
      and their relationship with glutamic acid decarboxylase antibodies.
AB  - OBJECTIVE: To study the clinical significance of thyroid autoantibodies in Thai
      patients with type 1 diabetes and their relationship with glutamic acid
      decarboxylase antibodies (GAD(65)Ab). METHODS: Thyroglobulin antibodies (TG-Ab)
      and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1
      diabetic patients. Forty-four patients also had GAD(65)Ab measured. Serum
      thyrotropin (TSH) was measured in all patients who had no history of thyroid
      disease regardless of thyroid antibody status. Clinical data including sex, age
      at onset and duration of diabetes, family history of diabetes, fasting c-peptide
      levels as well as frequencies of GAD(65)Ab were compared between patients with
      and without thyroid antibodies. GAD(65)Ab was also measured in 29 non-diabetic
      patients with hyperthyroid Graves' disease or Hashimoto thyroiditis as a control
      group. RESULTS: TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%)
      patients, respectively. Eight patients (16%) were positive for both antibodies.
      Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history
      of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly
      diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism
      at the time of the study. None of 34 patients without thyroid antibodies had
      thyroid dysfunction. Eight patients with positive thyroid antibodies but without
      clinical thyroid dysfunction and 21 patients without thyroid antibodies were
      followed for up to 3 years, two patients of the first group developed
      hypothyroidism, whereas none of the latter developed thyroid dysfunction. The
      frequency of thyroid dysfunction at the time of initial study was significantly
      higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and
      these patients who were initially euthyroid tended to have a higher risk of
      developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid
      antibodies was significantly increased in females and in those who had positive
      GAD(65)Ab. GAD(65)Ab was negative in all of the non-diabetic patients with
      autoimmune thyroid disease. CONCLUSIONS: About one-fourth of Thai patients with
      type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of
      thyroid antibodies was increased in female and in GAD(65)Ab positive patients.
      The presence of thyroid antibodies is associated with a higher frequency of and
      may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic
      patients.

PMID- 10963822
TI  - Ca(2+)-Mg(2+)-ATPase activity and ionized calcium in Type 2 diabetic patients
      with neuropathy.
AB  - Ca(2+)-Mg(2+)-ATPase is an important regulator of intracellular calcium
      concentration and therefore, of erythrocyte deformability. We have investigated
      the possible relationship between Ca(2+)-Mg(2+)-ATPase activity (ATPase) and
      ionized calcium (Ca(2+)), in diabetic patients with peripheral neuropathy. A
      total of 104 Type 2 diabetic patients (57 neuropathic and 47 non-neuropathic) and
      25 non-diabetic subjects were studied. After an overnight fast, blood was taken
      for Ca(2+)-Mg(2+)-ATPase activity, Ca(2+), Mg(2+), PTH and HbA(1c). The
      neuropathy study group had significantly lower levels of ATPase, 6.6 (95% CI, 5.6
      7.7) nmol/mg/min compared to controls 7. 1 (6.2-8.3) nmol/mg/min, P<0.001 and to
      diabetic patients without neuropathy 7.0 (6.0-8.1) nmol/mg/min, P<0.001. The
      study group had also lower levels of Ca(2+) (0.89+/-0.18 mmol/l vs. control
      1.08+/-0. 24 mmol/l, P<0.01 and non-neuropathic 0.98+/-0.27 mmol/l, P<0.05) and
      Mg(2+) (0.73+/-0.13 mmol/l vs. control 0.81+/-0.14 mmol/l, P<0. 05), despite
      similar PTH levels. In diabetic subjects, no correlation was found between ATPase
      or Ca(2+) with glucose, HbA(1c), age or duration of diabetes. We conclude that in
      patients with diabetic neuropathy there are abnormalities of Ca(2+)-Mg(2+)-ATPase
      activity and Ca(2+). This provides further support for the role of
      microangiopathy in the pathogenesis of neuropathy.

PMID- 10963823
TI  - Pharmacokinetics and pharmacodynamics of insulin aspart, a rapid-acting analog of
      human insulin, in healthy Japanese volunteers.
AB  - Pharmacokinetic and pharmacodynamic properties of a rapid-acting analog of human
      insulin, insulin aspart, were compared with those of soluble human insulin in
      Japanese healthy subjects. Subcutaneous single injections (0.025 and 0.05 U/kg
      body weight (BW)) of insulin aspart produced a significantly earlier peak of
      exogenous insulin level in comparison with human insulin (30.8+/-13.8 versus
      61.3+/-14. 6 min, P<0.9001 for 0.025 U/kg; and 39.2+/-18.8 versus 99.2+/-53.8
      min, P<0.005 for 0.05 U/kg). The peak serum level of insulin aspart was higher
      than that of human insulin (23.0+/-6.0 versus 9.9+/-3.1 microU/ml for 0.025 U/kg;
      and 30.9+/-9.2 versus 13.3+/-4.1 microU/ml for 0.05 U/kg, P<0.0001). The time to
      the minimal level of glucose after insulin aspart was significantly shorter
      compared with human insulin (P<0.05 for 0.025 U/kg BW and P<0.01 for 0.05 U/kg
      BW). The Delta change in blood glucose induced by insulin aspart was larger than
      that observed for human insulin at any dose (P<0.001). The repeated injection of
      insulin aspart before each meal also resulted in a rapid rise in exogenous
      insulin level with peak level obtained approximately 40 min after insulin aspart
      at any dose. When compared with results of other trials with insulin aspart, the
      present results showed that pharmacokinetic and pharmacodynamic profiles of the
      rapid-acting analog insulin aspart in Japanese subjects are no different from
      those in nonJapanese subjects.

PMID- 10963824
TI  - Inducible myocardial ischaemia in asymptomatic Type 2 diabetic patients.
AB  - BACKGROUND: to define the prevalence of inducible myocardial ischaemia in
      asymptomatic Type 2 diabetic patients and its relation to urinary albumin
      excretion rate (AER). METHODS: 98 Type 2 diabetic patients aged 56+/-7 years, and
      20 non-diabetic volunteers were recruited. Dypiridamole plus exercise thallium
      201 myocardial single photon emission computed tomography (SPECT) was performed
      in all participants. Exclusion criteria were: age <30 or >70 years, evidence of
      cardiovascular disease, anomalous ECG, autonomic neuropathy or serum creatinine
      level >177 micromol/l. RESULTS: 36 out of 98 diabetic patients (37%) showed
      abnormal thallium SPECT (considered as inducible myocardial ischaemia), versus
      one out of 20 (5%) in control group (odds ratio 7.3 (95% CI 1.1-50.5), P<0.005).
      Among diabetic patients, prevalence of inducible ischaemia was greater in those
      with higher urinary AER (AER <30:30-300:> 300 mg/24 h: 26: 53: 88%, and greater
      in the normoalbuminuric group compared to the control group (26 vs. 5%; P<0.05).
      An AER >30 mg/24 h was the only independent factor associated with inducible
      myocardial ischaemia in the multivariate analysis (P=0.009). CONCLUSIONS: raised
      urinary AER in asymptomatic diabetic patients is a risk factor for present
      myocardial ischaemia demonstrated by thallium dypiridamole tomography. The
      prevalence of inducible myocardial ischaemia in asymptomatic diabetic patients
      without known coronary disease is much higher than in non-diabetic population.

PMID- 10963825
TI  - Marriage rate and number of children among young adults with insulin-dependent
      diabetes mellitus in Japan.
AB  - The main purpose of our study was to identify the social circumstances and
      lifestyle of IDDM patients in Japan. The present study focused on the marriage
      status of both men and women with IDDM as well as the number of children of women
      with IDDM. A questionnaire was sent to hospitals across the country. Doctors
      handed it or mailed it to IDDM patients aged 18 years or older. Unsigned answer
      sheets were returned directly by the patients. Data on the marriage rate and
      number of children were obtained, and possible factors affecting these indices
      were assessed. One thousand and thirteen patients (354 men and 659 women)
      answered the questionnaire. Both men and women with IDDM were less likely to be
      married in comparison with age-matched Japanese. The number of children of
      married IDDM women in various age groups was also lower in comparison with the
      general Japanese female population. Several factors other than diabetes
      complications including job discrimination, high medical costs, and psychological
      pressures, were thought to be responsible for these results.

PMID- 10963826
TI  - Evaluation of a simple, random urine test for prospective analysis of proteinuria
      in Type 2 diabetes: a six year follow-up study.
AB  - AIM: To assess the usefulness of an estimated proteinuria (EPE) using the protein
      to creatinine ratio (P/C ratio) in a random urine sample for follow-up evaluation
      of kidney function in diabetic patients. RESEARCH DESIGNS AND METHODS: 410 newly
      registered Type 2 diabetic patients had annual follow-up for 6 years (M:F
      263:147). EPE was calculated by estimation of P/C ratio in random urine sample.
      Based on the EPE they were divided into those with normal protein excretion (<100
      mg/dl), mild proteinuria (100 to <500 mg/dl) and nephropathy (persistent
      proteinuria >500mg/dl) cases. The study subjects were divided into 4 groups based
      on the proteinuria status at follow-up. Anthropometry, measurement of blood
      pressure and retinopathy were carried out for all study subjects. RESULTS: at the
      baseline, 342 (83.4%) had normal protein excretion, 53 (12.9%) had mild
      proteinuria and 15 (3.7%) had nephropathy. At the follow-up the respective
      numbers were 276 (67.3%), 64 (15.6%) and 70(17%). During the study period
      nephropathy developed in 55 (13.4%) and mild proteinuria in 11 (2.7%).
      Nephropathy developed in 32 (6.7%) subjects in the non-proteinuria group and in
      23 (43.4%) of the mild proteinuric subjects. Conversion to nephropathy was
      greater in the latter group (chi(2)=41.6, P<0.0001). Nephropathy cases had higher
      duration of diabetes at the baseline (8.8+/-6.4 years) and at follow-up (7.1+/
      6.0 years) and higher prevalence of hypertension when compared with non
      proteinuric group (60 and 43.5% compared with 11.1%, P<0.01). New cases of
      hypertension were detected in 32.8% of proteinuric and 0.7% of normal protein
      excretion subjects (chi(2)=32. 24, P=0.0001). During the follow-up 55 of the 70
      nephropathy subjects (78.6%) developed retinopathy compared with ten out of the
      276 subjects with normal protein excretion (3.6%) (chi(2)=200.6, P=0. 0001).
      CONCLUSION: EPE is useful in serial evaluation of kidney function. The risk
      conferred by hypertension, mild proteinuria and duration of diabetes in producing
      nephropathy are also highlighted. EPE could be used in developing countries to
      assess the renal function on a follow-up basis.

PMID- 10963827
TI  - A national diabetes care and education programme: the Ghana model.
AB  - An account is given of how a national diabetes care and education programme was
      developed in Ghana, a developing country, through international collaboration of
      medical schools, industry and government health care institutions. The approach
      is by way of trained diabetes teams consisting of physicians, dietitians and
      nurse educators at two tertiary institutional levels (teaching hospitals) who in
      turn trained teams consisting of physicians, dietitians or diettherapy nurses,
      nurse educators and pharmacists at regional and district/sub-regional levels to
      offer care and education to patients and the community. In three years all
      regional and about 63% of sub-regional/district health facilities had trained
      diabetes health care teams, run diabetes services and had diabetes registers at
      these institutions. Additionally a set of guidelines for diabetes care and
      education was produced. All programme objectives with the exception of one
      (deployment of diabetes kits) were met. Distances to be travelled by persons with
      diabetes to receive diabetes care had been reduced considerably. The success of
      the project has given an impetus to the collaborators to extend the programme to
      the primary health care level. The continuing prohibitive prices of diabetes
      medications and supplies however, could be addressed by removing taxes on such
      supplies. The Ghana diabetes care model, a 'top-down' approach, initially
      involving two diabetes centres is recommended to other developing countries,
      which intend to incorporate diabetes care and education into their health care
      system.

PMID- 10963828
TI  - Homeostasis model assessment in a population with mixed ethnicity: the 1992
      Singapore National Health Survey.
AB  - We studied insulin resistance and beta-cell function with reference to ethnic
      group, glucose tolerance and other coronary artery disease risk factors in a
      cross section of the Singapore population which comprises Chinese, Malays and
      Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure,
      anthropometric data, blood lipids, glucose and insulin were assayed in the
      fasting state. Glucose and serum insulin were measured 2 h after an oral glucose
      challenge. Insulin resistance and beta-cell function were calculated using
      homeostasis model assessment. Asian Indians had higher insulin resistance than
      Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM)
      were associated with greater insulin resistance and impaired beta-cell function
      compared to normal glucose tolerance (NGT). Insulin resistance was positively
      correlated with blood pressure in women and total cholesterol, LDL cholesterol
      and triglyceride in both men and women. It was negatively correlated with HDL
      cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no
      significant correlations with the cardiovascular risk factors studied. It appears
      that both impaired beta-cell function and insulin resistance are important for
      the development of hyperglycemia whereas insulin resistance alone seems more
      important in the development of coronary artery disease as it correlates with
      several known coronary artery disease risk factors.

PMID- 10963829
TI  - Comparison of WHO and ADA criteria for diagnosis of glucose status in adults.
AB  - The aim was to compare the 1997 American Diabetes Association (ADA) and 1985 and
      1998 World Health Organisation (WHO) criteria for the diagnosis of diabetes and
      impaired glucose tolerance (IGT) by ethnicity and cardiovascular risk factors. We
      analysed the oral glucose tolerance tests carried out in a cross-sectional survey
      of 5816 New Zealand workers aged 22-78 years (4211 men, 1605 women) carried out
      between 1988 and 1990. Prevalence of diabetes was similar using ADA (3.1%)
      compared with the 1998 WHO criteria (3.0%). The overall prevalence rate of
      diabetes using the 1985 WHO criteria was only 1.5%. The prevalence rate of
      impaired fasting glucose (IFG) was the lowest in Europeans (7.3%) and highest in
      Asians (15.0%). The overall weighted kappa for agreement between the 1997 ADA and
      1998 WHO criteria was moderate (0.59), but varied between ethnic groups.
      Cardiovascular disease (CVD) risk factors were approximately more adverse across
      groups with IFG, normal (ADA)/IGT (WHO), IFG/IGT and diabetes compared with
      normal subjects. Compared to those with IFG, participants with the normal
      (ADA)/IGT (WHO) criteria differed in fasting and 2-h glucose, diastolic blood
      pressure, and urinary albumin levels, and the proportions of males and number
      with hypertension, but had a significantly adverse pattern of CVD risk factors
      compared to those with normal glycaemia. The 1988 WHO criteria using the OGTT
      provides additional information for classifying various categories of glucose
      intolerance that is not captured using the 1997 ADA fasting glucose criteria
      alone.

PMID- 10963830
TI  - Importance of OGTT for diagnosing diabetes mellitus based on prevalence and
      incidence of retinopathy.
AB  - Study was made on the necessity and importance of the oral glucose tolerance test
      (OGTT) for diagnosing diabetes mellitus based on prevalence and incidence of
      diabetic retinopathy. Subjects were 12208 persons undergoing OGTT between 1965
      and 1997. The prevalence of retinopathy was significantly elevated with FPG>/=126
      and 2-h PG>/=198 mg/dl. The incidence of retinopathy was 15-30/10000 person-years
      (PY) with FPG<125, but with FPG of 126-139 it was significantly higher (69/10000
      PY) and at 140-199 mg/dl it was elevated to 139/10000 PY. Subjects were
      classified at initial test into FPG<110, 110-125, 126-139, and >/=140 and further
      into 2-h PG<200 and >/=200 mg/dl for comparison with the incidence of
      retinopathy. Even with the same FPG, the incidence was two- to threefold higher
      with 2-h PG>/=200 mg/dl, indicating that 2-h PG was highly associated with the
      incidence of retinopathy. As for IFG, the prevalence of diabetes as defined by 2
      h PG>/=200 in the OGTT increased with elevated FPG, and 33.7% of IFG cases showed
      2-h PG>/=200 mg/dl. Based on the prevalence and incidence of retinopathy, we
      conclude that 126 mg/dl FPG is an appropriate cut-off level, and the OGTT is
      important for diagnosing mild diabetes mellitus.

PMID- 10963831
TI  - Considerations about the threshold value of microalbuminuria in patients with
      diabetes mellitus: lessons from an 8-year follow-up study of 599 patients.
AB  - OBJECTIVE: To examine the validity of the time honored threshold value for
      microalbuminuria of 30 mg/24 h, by analyzing an 8-year follow-up data of 599
      patients with diabetes mellitus type 2, normal blood pressure and base-line
      albumin excretion rate (AER) </=30 mg/24 h. PATIENTS: The patients were allocated
      to three groups according to the baseline values of AER. Group I: 0-10 mg/24 h;
      Group II: 10.1-20 mg/24 h; Group III: 20.1-30 mg/24 h. RESULTS: Progression to
      microalbuminuria during follow-up occurred in 25.3, 47.3 and 85.3% of the
      patients in Group I, II and III, respectively. Compared to Group I, the risk to
      progress to microalbuminuria was 2. 34 (95% CI 1.32-4.43, P=0.029) in patients of
      Group II and 12.36 (95% CI 8.9-16.5, P=0.0001) in Group III. The average annual
      decline in glomerular filtration rate (GFR) was 1.19, 1.64 and 2.52 ml/min per
      year, respectively in the three groups. The correlation between baseline AER
      values and subsequent decline in GFR was exponential without a clear threshold
      value. Compared to Group I, the odds ratio for any cardiovascular end point (e.g.
      death, non-fatal myocardial infarction etc.) was 1.9 (95% CI 0.8-2.5, P=0.22) for
      patients of Group II and 9.8 (95% CI 6.7-12.3, P=0.001) for Group III.
      CONCLUSIONS: The present study shows that patients with baseline AER values of
      20.1-30 mg/24 h show an accelerated decline in GFR and significantly higher risk
      for cardiovascular events than patients with AER values below 20 mg/24 h. Though
      AER is obviously a continuous variable, the arbitrary threshold value for
      screening and for preventive strategies should probably be set at 20 rather than
      at 30 mg/24 h.

PMID- 10963833
TI  - Preface

PMID- 10963832
TI  - S20G mutation of the amylin gene in Japanese patients with type 2 diabetes.

PMID- 10963834
TI  - Pathogenesis of osteoporosis and challenges for drug delivery.
AB  - Bone remodeling is under the control of local factors produced in the bone
      microenvironment. Many of the mechanisms responsible for coordination of activity
      between osteoclasts and osteoblasts, and how they are dysregulated in diseases of
      bone loss such as osteoporosis, are now being clarified. This leads to the
      possibility that bone remodeling can be manipulated by pharmacological means to
      reverse the changes caused by common bone diseases. However, many of the
      potential drugs suffer from non-selectivity in their effects. Targeting of drugs
      to active skeletal sites is of major interest to the pharmaceutical industry, and
      there are interesting and exciting possibilities which could lead to more
      specific therapies for the common diseases of bone loss. These will be reviewed
      in this chapter.

PMID- 10963835
TI  - Administration routes and delivery systems of bisphosphonates for the treatment
      of bone resorption.
AB  - Geminal bisphosphonates (BPs) are a class of drugs considered to be stable
      analogs of pyrophosphate (P-O-P), a physiological regulator of calcification and
      bone resorption. A number of BPs have been approved for clinical use in Paget's
      disease, hypercalcemia of malignancy, and osteoporosis. The major disadvantage of
      the clinically utilized BPs is their poor oral absorption from the GI tract,
      typically less than 1% is absorbed. In addition, the BPs have been associated
      with adverse gastrointestinal effects in humans. The challenge for novel drug
      delivery systems is to achieve improved bioavailability and safety. In the first
      part of this review, we discuss the bioavailability of BPs, the effect of food on
      the absorption of BPs, the mechanism of BPs' absorption and the adverse
      gastrointestinal effects. In the second part of the review, various methods that
      have been used for improving the bioavailability of BPs are described. Dosage
      form strategies reviewed include the use of particular formulations for
      increasing oral absorption as well as decreasing adverse gastrointestinal
      effects, absorption enhancers, BP compounds and the solubility of their calcium
      complex/salts, and the prodrug approach. Because of the poor GI absorption,
      attempts have been made to enhance the bioavailability of BPs by several
      parenteral routes other than i.v. injections. Description of nasal
      administration, s.c. and i.m. injections, BP implants and targeted osteotropic
      delivery systems are reviewed.

PMID- 10963836
TI  - Transdermal delivery of drugs for the treatment of bone diseases.
AB  - The current status of transdermal drug delivery for the treatment of bone
      diseases is described in this review. The structure, physiology and function of
      skin and their importance in determining delivery into and across skin are
      discussed. Special emphasis has been devoted to a description of the major
      pathways of transport across the skin and the quite continuing controversy over
      the importance of the transfollicular route. An overview of anatomic site
      dependent drug absorption is also provided and is particularly relevant to
      determination of transdermal patch location. Brief descriptions of the criteria
      for selection of transdermal drug candidate, transdermal patch designs and
      currently marketed transdermal products are also included. Transdermal estradiol
      delivery systems are examined in more detail for their clinical and biological
      effects. Finally, the feasibility of delivering drugs such as bisphosphonates
      across skin is discussed.

PMID- 10963837
TI  - Oral delivery of salmon calcitonin.
AB  - Calcitonin plays a crucial role in both calcium homeostasis and bone remodeling.
      Establishing an oral delivery system for CT is of great importance since CT is
      currently administered only parenterally or nasally. Poor absorption and rapid
      proteolytic degradation have impeded the clinical development of an orally
      administered sCT drug product. Potential approaches to enhance sCT absorption
      include the use of formulation additives in the drug product to transiently
      modulate the intestinal environment or targeting specific intestinal regions that
      may have favorable peptide delivery properties (e.g., low residual volume, high
      absorptive surface area or reduced enzymatic activity). Potential approaches to
      limit the activity of intestinal enzymes include adjusting the pH of the
      intestinal contents to the pH minima of specific enzymes or maintaining high
      local drug concentrations in order to saturate enzyme systems. In this review,
      pharmacokinetic studies elucidating the rate-limiting steps for achieving
      adequate sCT oral bioavailability are detailed. Further, several approaches for
      enhancing the oral absorption of sCT are presented. Specific emphasis is placed
      on regio-specific targeting (e.g., intestinal regional differences in dilution
      and spreading, etc.) and modulation of the intestinal environment (e.g., changing
      pH, etc.). The approaches are evaluated in in vitro and in vivo models. Finally,
      this paper closes with a brief section of concluding remarks.

PMID- 10963838
TI  - Pulmonary delivery of drugs for bone disorders.
AB  - As the population ages, osteoporosis becomes a growing public health concern.
      Current treatments provide patients with limited clinical improvement, numerous
      side effects, and no cure. The naturally-occurring peptides calcitonin and
      parathyroid hormone, which regulate bone metabolism, offer alternative treatment
      options. Clinical studies indicate the usefulness of calcitonin and parathyroid
      hormone in osteoporosis and Paget's disease of bone. For the peptides to become
      viable therapies, formulations must be developed that bypass the need for
      injection. Pulmonary delivery of calcitonin and parathyroid hormone appears
      likely in the near future.

PMID- 10963839
TI  - Calcium-level responsive controlled drug delivery from implant dosage forms to
      treat osteoporosis in an animal model.
AB  - The effects of plasma calcium levels on estradiol release from a self-setting
      apatite bone cement containing 0.5% estradiol and on the bone mineral density
      (BMD) of ovariectomized rats were investigated. Apatite cement consisting of an
      equimolar mixture of tetracalcium phosphate, dicalcium phosphate dihydrate and
      0.5% beta-estradiol was prepared. The in vitro release profiles from the cements
      in simulated body fluid containing 0, 5 and 10 mg/100 ml calcium indicated that
      estradiol release rate decreased with increasing calcium concentration in the
      dissolution medium. After subcutaneous implantation of the cement, in vivo
      estradiol release in diseased rats (ovariectomized rats on a low calcium diet)
      was significantly higher than that in normal rats. The diseased rats maintained a
      low calcium level during drug release. The bone mass of the recovery model rat
      was greater after the experiment than before. The results suggested that the
      severity of osteoporosis in this animals can be reduced by the implantation of
      this estradiol-loaded apatite cement.

PMID- 10963842
TI  - High prevalence of atypical adenomatous hyperplasia of the lung in autopsy
      specimens from elderly patients with malignant neoplasms.
AB  - Atypical adenomatous hyperplasia (AAH) is a possible precursor lesion of
      adenocarcinoma of the lung, but there have been no reports of AAH focusing on
      autopsy studies of the lungs of elderly patients, who have higher lung cancer
      mortality rates. We intended to clarify the characteristics of AAH in the general
      elderly population on the basis of the findings in autopsy cases. A total of 19
      AAH lesions were found microscopically in 16 out of 241 autopsy cases (6.6%). AAH
      was found in only two cases of adenocarcinoma among 28 lung cancer cases. p53
      immunoreactivity was observed in one of 11 low-grade AAH lesions (9.1%), but in
      three of four high-grade AAH lesions (75%, P=0.03) and the cases of high-grade
      AAH were more frequently positive for Ki-67 and CEA than the low-grade cases and
      less positive for pro-surfactant apoprotein C. Four of 123 patients without
      malignant neoplasms (3.4%) and 12 of 118 patients with malignant neoplasms
      (11.1%) had AAH (P=0.03). The finding that AAH was more common in the cases with
      malignancy than in those without malignancy indicated that genesis of AAH may be
      closely associated with that of malignant neoplasms.

PMID- 10963840
TI  - Second-line chemotherapy for recurrent non-small cell lung cancer: do new agents
      make a difference?
AB  - After a certain degree of nihilism, chemotherapy has become the standard
      treatment for advanced and metastatic non-small cell lung cancer (NSCLC). The new
      chemotherapeutic drugs (vinorelbine, taxanes, gemcitabine, and irinotecan) and
      their associations with cisplatin have shown better response rates and survival
      in comparison with the standard regimens. This increase of survival is the main
      motive of the possible consideration of a second-line therapy in NSCLC patients.
      To this regard, the most promising drug may be docetaxel that, in a randomized
      trial comprising a best supportive care arm (BSC), documented a response rate of
      7.6%, a longer median survival (31 weeks versus 21 of BSC), and a statistically
      better quality life. Other phase II studies obtained a response rate of 20% and 1
      year survival of 40% using docetaxel. Also gemcitabine has shown interesting
      results in this setting, with a 19% response rate and a median and 1-year
      survival rate of 34 weeks and 45%, respectively. The activity of paclitaxel is
      not well defined because of conflicting results and deserves further
      investigations, while the efficacy of vinorelbine and irinotecan has been dismal.
      Large randomized trials comparing the treatment arm with best supportive care and
      a careful analysis of quality of life and cost-effectiveness will be needed to
      clarify the role of second-line therapy in advanced NSCLC.

PMID- 10963844
TI  - Phase II study of tamoxifen, ifosfamide, epirubicin and cisplatin combination
      chemotherapy in patients with non-small cell lung cancer failing previous
      chemotherapy.
AB  - We conducted a phase II study of tamoxifen, ifosfamide, epirubicin, and cisplatin
      (TIEP) chemotherapy in patients with non-small cell lung cancer (NSCLC) who had
      failed previous chemotherapy, in order to assess the response and toxicity of
      TIEP. Between November 1997 and May 1999, 25 patients were treated. Twelve of the
      25 patients (48%) had been previously treated with cisplatin-based combination
      chemotherapy. TIEP doses were tamoxifen 60 mg oral twice daily on days 1-3;
      ifosfamide 2.4 g/m(2) intravenous infusion (IV) 60 min with mesna on day 2;
      epirubicin 40 mg/m(2) IV bolus on day 2; and cisplatin 50 mg/m(2) IV 60 min on
      day 2 every 4 weeks for up to six cycles. Seventy one cycles were given to 25
      patients, with a median of three cycles (range one to six cycles). All patients
      were evaluable for toxicity profile and response rate. As expected, the major
      toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 15 patients
      (60%) during treatment, as well as in 31% of the total courses. Febrile
      neutropenia occurred in two patients. No toxic death occurred in this study.
      Grade 3 thrombocytopenia occurred in five patients with five cycles. Toxicities
      other than myelosuppression were few and mild in severity. After two cycles of
      treatment, five of 25 patients (20%) had a partial response (95% confidence
      interval 4.3-35.7%). Among 12 patients previously treated with cisplatin-based
      chemotherapy, three patients (25%) achieved a partial response. The median time
      to disease progression was 4.9 months and median survival was 7.7 months. The
      response rate and median survival were better than in our previous study of
      salvage chemotherapy with ifosfamide, 5-FU, and leucovorin; and with ifosfamide,
      epirubicin, 5-FU, and leucovorin. In conclusion, TIEP appears to be an active
      combination regimen with an acceptable toxicity profile in Chinese patients with
      NSCLC who have failed previous chemotherapy.

PMID- 10963843
TI  - Thoracic radiotherapy and daily vinorelbine as radiosensitizer in locally
      advanced non small cell lung cancer: a phase I study.
AB  - Experimental studies have shown that vinorelbine is a powerful radiosensitizer in
      vitro. To date, no reports on clinical activity of the single agent vinorelbine
      as radiosensitizer have been published. The aim of the present phase I study was
      to determine the maximum tolerated dose (MTD) of vinorelbine administered daily
      concurrently with thoracic radiotherapy, with or without amifostine support, in
      the treatment of locally advanced non small cell lung cancer. In vitro studies
      have shown that vinorelbine can potentiate the antitumor effects of radiation
      therapy. Amifostine is a sulphydril compound that has shown to protect normal
      tissues from chemotherapy and radiotherapy-induced toxicities. Radiotherapy
      lasted 6 weeks and the total dose was 55 Gy. The daily fraction was 1.8 Gy,
      administered 5 days a week for 5 weeks and increased to 2.0 Gy during the sixth
      and last week. Concurrent vinorelbine was administered daily with a planned
      escalation of the dose from 4, to 5 and 6 mg/m(2). Fourteen patients were
      enrolled in the study. The first dose of vinorelbine was 4 mg/m(2) and it showed
      to be feasible without dose-limiting toxicity (DLT). Instead, the second dose
      level of 5 mg/m(2) was unfeasible because three out of six patients had DLT
      (grade 4 neutropenia, treatment interruption longer than 2 weeks for prolonged
      grade 2 neutropenia and treatment interruption longer than 2 weeks for prolonged
      grade 3 esophagitis together with grade 4 dyspnea). At that time, the study
      continued adding amifostine to vinorelbine in order to increase its MTD.
      Amifostine was administered by means of subcutaneous injection 15 min before each
      radiotherapy fraction at the fixed dose of 300 mg/m(2). However, 5 mg/m(2) of
      vinorelbine were considered unfeasible even with amifostine support because three
      out of five patients showed DLT (grade 4 neutropenia, febrile grade 4 neutropenia
      and grade 3 liver toxicity). Among 14 patients enrolled in the study, eight
      completed the planned treatment because six patients experienced DLT, which
      determined treatment interruption. Overall, four partial and two complete
      responses were observed. Two partial and one complete response were observed in
      those three patients who had been treated with the first dose of vinorelbine. In
      conclusion, our data show that the MTD of daily vinorelbine is 4 mg/m(2).
      Therefore, this is the recommended dose of daily vinorelbine to be administered
      with concurrent thoracic radiotherapy in a phase II trial. Finally, amifostine
      administered subcutaneously failed to increase the MTD of daily vinorelbine.

PMID- 10963841
TI  - Differentiation of malignant from benign solitary pulmonary lesions using chest
      radiography, spiral CT and HRCT.
AB  - OBJECTIVE: The aim of this prospective study was to summarize all of the
      qualitative and quantitative imaging criteria for the differentiation of solitary
      pulmonary lesions (SPLs) as malignant (MSPLs) or benign (BSPLs) described in the
      literature and to critically analyze the different characteristics in order to
      evaluate their clinical importance and usefulness as criteria for a
      discrimination during the primary diagnostic assessment of SPLs using chest
      radiography, spiral computed tomography (SCT) and high-resolution computed
      tomography (HRCT). MATERIALS AND METHODS: SPLs were examined, evaluated and then
      completely removed by surgery in 104 consecutive patients (MSPLs n=81, BSPLs
      n=23). No SPL was excluded by size. Chest radiography was performed with frontal
      and lateral views, SCT was carried out with a slice thickness of 8 mm and HRCT
      with a slice thickness of 1 mm and a 12-cm field of view. RESULTS: All the
      characteristics which enabled a reliable differentiation of MSPLs from BSPLs were
      characteristics which were observed significantly more frequently in MSPLs than
      BSPLs. Useful characteristics for the differentiation of MSPLs from BSPLs (1)
      using chest radiography were the indistinct edge (P<0.0001) and a ground-glass
      opacity of the lung parenchyma adjacent to the SPL (P<0. 05); (2) using SCT the
      presence of spicules (P<0.0005), the vessel sign (P<0.0005), necrotic areas
      (P<0.001), spicules extending to the visceral pleura (P<0.005), circumscribed
      pleural thickening (P<0. 005), inhomogeneity (P<0.01), a ground-glass opacity of
      the lung parenchyma adjacent to the SPL (P<0.01), the lesion density (P<0.05),
      pleural retraction (P<0.05) and the bronchus sign (P<0.05); and (3) using HRCT
      the presence of spicules (P<0.00005), spicules extending to the visceral pleura
      (P<0.0005), the vessel sign (P<0.0005), pleural retraction (P<0.001),
      circumscribed pleural thickening (P<0. 001), the bronchus sign (P<0.005), a
      ground-glass opacity of the lung parenchyma adjacent to the SPL (P<0.01), the
      lesion density (P<0.05) and the length of spicules (P<0.05). Using any one of the
      characteristics with a significance level of P<0.01, the identification of MSPLs
      (1) using chest radiography showed a sensitivity of 64.2% and a specificity of
      82.6% (accuracy of 68.3%); (2) using SCT a sensitivity of 88.9% and a specificity
      of 60.9% (accuracy of 82.7%); and (3) using HRCT a sensitivity of 91.4% and a
      specificity of 56.5% (accuracy of 83.7%). CONCLUSIONS: Using chest radiography,
      SCT and HRCT, a precise morphological assessment of the periphery of the
      pulmonary lesion and the adjacent visceral pleura is necessary to distinguish
      MSPLs from BSPLs. In this respect SCT and HRCT are useful in differentiation of
      MSPLs from BSPLs. However, metastases strongly resembled benign lesions in terms
      of size and edge type and chronic inflammatory pseudotumors as a group mimic
      MSPLs.

PMID- 10963845
TI  - Pulmonary resection for lung cancer in HIV-positive patients with low (<200
      lymphocytes/mm(3)) CD4(+) count.
AB  - The clinical improvement obtained with combination treatment has modified the
      therapeutic approach of lung cancer in HIV-positive patients. Aggressive surgical
      treatment has become a viable option for those patients in whom the CD4(+) cell
      count was greater than 200 lymphocytes/mm(3). We recently extended our surgical
      indications to include two HIV-positive patients with lung cancer (stage IIIA and
      IIB) and low (<200 lymphocytes/mm(3)) CD4(+) count. Both patients underwent a
      lobectomy and mediastinal nodal dissection. The postoperative course was
      uneventful. No evidence of recurrent cancer was seen at 12 and 20 months after
      the operation. Based on this limited experience, we conclude that a low CD4(+)
      count should not represent, per se, an exclusion criterion for the surgical
      treatment of pleuropulmonary conditions in HIV-positive patients.

PMID- 10963846
TI  - Co-expression of epidermal growth factor receptor and transforming growth factor
      alpha is independent of ras mutations in lung adenocarcinoma.
AB  - The interaction of epidermal growth factor receptor (EGFR) and its ligand
      transforming growth factor-alpha (TGF-alpha) leads to an autocrine activation of
      the ras signaling pathway and putatively its oncogenic activity. It is thus
      hypothesized that the co-overexpression of EGFR-TGFalpha will be redundant hence
      rare in tumors with oncogenic ras mutations. To test this hypothesis, we studied
      by immunohistochemistry the expression of EGFR and TGF-alpha in primary non small
      cell lung cancers. Such putative EGFR autocrine loop activation was found in 73%
      of squamous cell carcinomas that rarely develop ras mutations. In contrast, EGFR
      TGFalpha co-expression occurred with equal frequency in adenocarcinomas
      irrespective of their ras genotype. The results indicate that EGFR autocrine loop
      activity in adenocarcinoma may have alternative signaling activities aside from
      the activation of ras-MAP kinase pathway.

PMID- 10963847
TI  - Stimulation of Ca(2+)-dependent exocytosis and release of arachidonic acid in
      cultured mast cells (RBL-2H3) by quercetin.
AB  - Basic secretagogues, such as compound 48/80, stimulate secretion in rat
      peritoneal mast cells by directly activating the heterotrimeric G-protein Gi(3)
      (Aridor M, et al. Science 1993;262:1569-72). Cultured RBL-2H3 mast cells do not
      normally respond to basic secretagogues, but acquire such responsiveness upon
      prolonged exposure to the kinase inhibitor, quercetin, which also increases the
      cellular level of Gi(3) (Senyshyn J, Baumgartner RA, Beaven MA. J Immunol
      1998;160:5136-44). Expression of a GTPase-deficient mutant of Galphai(3) in RBL
      2H3 cells results in the stimulation of Ca(2+)-triggered exocytosis and release
      of arachidonic acid (AA) (Zussman A, Hermuet S, Sagi-Eisenberg R. Eur J Biochem
      1998;258:144-6). Here we show that long-term incubation with quercetin markedly
      stimulates Ca(2+)-triggered exocytosis and release of AA from the RBL-2H3 cells.
      We further show that membranes derived from such quercetin-treated cells display
      a reduced GTPase, but not ATPase, activity. Taken together with our previous
      observations, these results further implicate Gi(3) as one of the cellular
      targets through which quercetin confers responsiveness towards the family of
      basic secretagogues.

PMID- 10963848
TI  - The anti-allergic drug histaglobin inhibits NF-kappaB nuclear translocation and
      down-regulates proinflammatory cytokines.
AB  - The transcription factor NF-kappaB is the central regulator for the expression of
      various genes involved in inflammation, infection and immune response including
      the genes for IL-1beta, TNF-alpha, IL-6 and leukocyte adhesion molecules. Here,
      we show that the anti-allergic drug histaglobin down-regulates the release of IL
      1beta, TNF-alpha, IL-6 and IL-10 in human peripheral blood mononuclear cell
      cultures. This down-regulatory effect becomes even more pronounced when the
      cultures are simultaneously activated with the T-lymphocyte mitogen
      phytohemagglutinin (PHA) or with the B-lymphocyte and macrophage activator
      lipopeptide (P(3)CSK(4)). We also demonstrate that histaglobin inhibits the
      nuclear translocation of NF-kappaB in response to TNF-alpha or lipopolysaccharide
      (LPS) in bone marrow-derived macrophages of Balb/c mice. The inhibitory effect of
      histaglobin on NF-kappaB activation and cytokine release might be responsible for
      its anti-allergic effect as demonstrated in clinical studies.

PMID- 10963850
TI  - Inhibition of lipopolysaccharide-induced I-kappaB degradation and tumor necrosis
      factor-alpha expression by acriflavine, an antimicrobial agent.
AB  - Acriflavine neutral (ACF) has been used for treatment of microbial infections for
      humans and fishes. Effects of ACF on the nuclear factor-kappaB (NF-kappaB)
      activation and tumor necrosis factor-alpha (TNF-alpha) production by
      lipopolysaccharide (LPS), an endotoxin, were examined in rat and RAW264.7 cells.
      Gel retardation analysis revealed that LPS (1 microg/kg) activated NF-kappaB in
      the liver, whereas pretreatment of rats with ACF (10 mg/kg) completely prevented
      the NF-kappaB activation. Selectivity of the NF-kappaB DNA binding was confirmed
      by immunodepletion with anti-p65 and anti-p50 antibodies. Translocation of NF
      kappaB to the nucleus is preceded by phosphorylation and proteolytic degradation
      of inhibitor-kappaBalpha (I-kappaBalpha) subunit. Whereas the level of I
      kappaBalpha protein was rapidly decreased after treatment of rats with LPS (1
      microg/kg), ACF treatment prior to LPS attenuated the decrease in I-kappaBalpha
      protein level. LPS-induced increase in the production of TNF-alpha, the principal
      inflammatory mediator, was prevented by ACF pretreatment by 80%. Stimulation of
      RAW264.7 cells with 1 microg/ml of LPS caused an increase in DNA binding activity
      of NF-kappaB, which was 80% inhibited by 1 microg/ml of ACF. LPS reduced I
      kappaBalpha level in RAW264.7 cells by 77%. ACF attenuated LPS-induced decrease
      in I-kappaBalpha protein in a concentration-dependent manner. Production of TNF
      alpha by LPS from RAW264.7 cells was decreased by 84% in the presence of ACF.
      Data showed that ACF inhibited LPS-induced NF-kappaB activation through
      inhibition of I-kappaBalpha degradation and TNF-alpha production in both rat and
      RAW264.7 cells. Inhibition of NF-kappaB activation and TNF-alpha production may
      be associated with the anti-inflammatory activity of ACF.

PMID- 10963849
TI  - Onapristone (ZK299) blocks the suppressive effect of progesterone, but not that
      of dexamethasone, on inducible nitric oxide synthase gene expression and nitric
      oxide production in murine macrophages.
AB  - Suppressive effects of progesterone on inducible nitric oxide synthase (iNOS)
      protein expression and nitric oxide (NO) production in murine peritoneal
      macrophages in response to bacterial lipopolysaccharide (LPS) and the inhibition
      of the suppressive activity of progesterone by onapristone (ZK299), a synthetic
      progesterone inhibitor, were studied. Progesterone suppressed dose-dependently
      LPS-induced NO production by macrophages, and scarcely detectable expression of
      iNOS was seen in the macrophages. ZK299 liberated the macrophages from the
      inhibitory effect of progesterone. Although dexamethasone, a synthetic
      glucocorticoid, can potently suppress LPS-induced NO production by macrophages,
      ZK299 did not liberate the suppression by dexamethasone, suggesting that these
      two corticosteroids induce suppression through independent mechanisms. RT-PCR
      analysis showed that murine macrophages expressed no progesterone-receptor. These
      findings indicate that the inhibitory effect of progesterone occurs at least on
      the level of iNOS protein expression in the signaling pathway after the LPS
      stimulus. Furthermore, our present data may suggest the existence of a yet
      unknown type of progesterone-receptor in murine macrophages, the binding to which
      is responsible for the inhibitory effect of progesterone, or that progesterone
      may act non-specifically on the macrophages without involvement of any receptor.

PMID- 10963851
TI  - Comparison of inhibitory effects of local anesthetics on immune functions of
      neutrophils.
AB  - Immunological effects of a variety of local anesthetics on adhesion,
      phagocytosis, and the production of superoxide anion and hydrogen peroxide by
      neutrophils were compared. Neutrophils were isolated by peritoneal lavage from
      rats, 4 h after injection of 1% glycogen. Lidocaine, mepivacaine, procaine,
      prilocaine and tetracaine at 1 mg/ml inhibited adhesion, phagocytosis, and the
      production of superoxide anion and hydrogen peroxide in neutrophils. Moreover,
      lidocaine, mepivacaine, procaine and prilocaine at 0.1 mg/ml inhibited the
      production of superoxide anion and hydrogen peroxide but not adhesion or
      phagocytosis. In contrast, tetracaine at 0.1 mg/ml inhibited phagocytosis, and
      the production of superoxide anion and hydrogen peroxide but not adhesion. At
      0.01 mg/ml, however, tetracaine inhibited the production of superoxide anion and
      hydrogen peroxide; in contrast, other drugs failed to affect neutrophil function.
      These results suggest that the local anesthetics may affect adhesion,
      phagocytosis, and the production of superoxide anion and hydrogen peroxide by
      neutrophils.

PMID- 10963852
TI  - Inhibition of basophil histamine release by tyrosine kinase and
      phosphatidylinositol 3-kinase inhibitors.
AB  - It has been demonstrated that tyrosine kinase (TK) and phosphatidylinositol 3
      kinase (PI3-K) are involved in IgE-mediated stimulation of human basophils;
      conversely, little is known about the biochemical pathways activated by IL-3 and
      GM-CSF. The aim of this study was to evaluate the effects of TK and PI3-K
      inhibitors on basophil histamine release induced by anti-IgE, IL-3 and GM-CSF.
      Since IL-3 and GM-CSF cause histamine release from normal human basophils only
      when the inhibitory effect of extracellular Na(+) has been removed, peripheral
      blood leukocytes were suspended in isotonic solutions containing either 140 mM
      NaCl or 140 mM N-methyl-D-glucamine(+). After stimulation with anti-IgE, IL-3 or
      GM-CSF, histamine release was measured by an automated fluorometric method. The
      effects of preincubation with four different TK inhibitors (AG-126, genistein,
      lavendustin A, tyrphostin 51) and one PI3-K inhibitor (wortmannin) were
      evaluated. AG-126, genistein and lavendustin A exerted a significant dose
      dependent inhibitory effect on basophil histamine release induced by anti-IgE
      (either in high or in low Na(+) medium), IL-3 and GM-CSF. Among the TK
      inhibitors, lavendustin A exerted the most potent activity, followed by AG-126
      and genistein. Tyrphostin 51 caused a weak inhibition of histamine release
      induced by IL-3, GM-CSF and anti-IgE in a low Na(+) medium, but not in a
      physiological Na(+)-containing medium. The PI3-K inhibitor wortmannin exerted the
      most effective inhibitory activity on the histamine release induced by the three
      agonists. The combined effects of lavendustin A and wortmannin were less than
      additive, suggesting that TK and PI3-K are involved in the same activation
      pathway in human basophils. These results suggest a possible role of TK and PI3-K
      in basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. TK and PI3-K
      are indeed potential therapeutic targets for antiallergic drugs.

PMID- 10963853
TI  - Vaccination against nicotine during continued nicotine administration in rats:
      immunogenicity of the vaccine and effects on nicotine distribution to brain.
AB  - Vaccination against nicotine has been proposed as a potential treatment for
      nicotine dependence. Because vaccination may take months to elicit satisfactory
      antibody levels, the clinical usefulness of this approach will be enhanced if
      vaccination can be accomplished during continued nicotine intake (e.g., before a
      smoker quits). The current study examined the immunogenicity of a nicotine
      conjugate vaccine during continued nicotine dosing in rats, and its effects on
      nicotine distribution to brain. In the first experiment, nicotine was
      administered over 11 weeks as 20 intra venous (i.v.) bolus injections per day
      during the rat's active cycle to simulate the usual pattern of nicotine intake
      from cigarette smoking. In the second experiment, rats received a continuous s.c.
      infusion of nicotine by osmotic pump for 11 weeks to provide serum nicotine
      concentrations equivalent to those of a heavy smoker and 24 h/day nicotine
      exposure. Nicotine-specific antibody titers after the third booster dose were not
      compromised by either regimen of concurrent nicotine administration compared to
      those of rats receiving saline. A single additional i.v. nicotine dose was
      administered at the end of each experiment. The distribution of this single
      nicotine dose to brain was reduced by 40-60% in vaccinated rats compared to
      controls. Vaccine efficacy in reducing nicotine distribution to brain was not
      compromised by concurrent nicotine administration. These data suggest that
      vaccination during concurrent nicotine administration is feasible, and that the
      ability of vaccination to reduce nicotine distribution to brain is preserved even
      after months of nicotine dosing at rates approximating cigarette smoking.

PMID- 10963855
TI  - "Mechanism of thymocyte apoptosis induced by serum of tumor-bearing host: the
      molecular events involved and their inhibition by thymosin alpha-1". By rajat
      roy, sukh mahendra singh, anil shanker. International journal of
      immunopharmacology 22 (4) 309--321

PMID- 10963854
TI  - Influence of melatonin on immunotoxicity of lead.
AB  - The results suggested that immunotoxicity induced by lead [Pb, as Pb(NO(3))(2)]
      was significantly restored or prevented by melatonin (MLT). MLT (10 or 50 mg/kg)
      was orally administered to ICR mice daily for 28 days, and Pb was also
      administered at 35 mg/kg in the same way 2 h after the administration of MLT, and
      the normal mice were given vehicle. Within the Pb plus MLT-treated group, the
      body weight gains and the relative thymus weights were significantly increased
      when compared with the treatment of Pb alone. The relative spleen and liver
      weights were increased by the treatment of Pb alone, and then restored to normal
      value by MLT treatment. Hemagglutination (HA) titer, plaque-forming cell response
      to sheep red blood cell (SRBC), and secondary IgG antibody response to BSA were
      significantly enhanced in the Pb plus MLT-treated mice, as opposed to when
      compared with the treatment of Pb alone. The mitogenic response of splenic T cell
      to concanavalin A and that of B cells to lipopolysaccharide was remarkably
      increased by MLT treatment when compared with treatment of Pb alone. Splenic
      CD4(+)cells were significantly increased by MLT treatment when compared with
      treatment of Pb alone. In case of CD8(+) cells, the slight enhancement was
      observed in MLT treatment. Splenic T and B cells were significantly increased by
      MLT treatment when compared with the treatment of Pb alone. The natural killer
      cell, phagocytic activity and the number of peripheral leukocytes were
      significantly enhanced in Pb plus MLT-treated mice when compared with the
      treatment of Pb alone.

PMID- 10963856
TI  - Using Haber's law to define the margin of exposure.

PMID- 10963857
TI  - The use of Haber's law in standard setting and risk assessment.
AB  - Haber's Law simply states that the incidence and/or severity of a toxic effect
      depends on the total exposure, i.e. exposure concentration (c) rate times the
      duration time (t) of exposure (c x t). This rule, within constraints, is often
      used in setting exposure guidelines for toxic substances. Establishing reference
      doses (acceptable daily intakes) for long-term exposures when only the results of
      short-term studies are available requires the use of an uncertainty (safety)
      factor. The value of this uncertainty factor often approximates a value
      comparable to Haber's Law for extrapolation from short-term to long-term exposure
      durations. As a default procedure, cancer risk estimates are generally based on
      the average lifetime daily dose which is derived from the total cumulative
      exposure, i.e. Haber's (c x t). This has been shown both theoretically and
      empirically to be valid within a factor of 20 for carcinogenesis. This provides
      some credence for the use of an additional safety factor of 10, in some
      instances, for exposures of children to carcinogens. Finally, a generalization of
      Haber's Law, exposure concentration raised to a power times exposure duration, is
      discussed.

PMID- 10963858
TI  - Haber's rule: a special case in a family of curves relating concentration and
      duration of exposure to a fixed level of response for a given endpoint.
AB  - The concept that the product of the concentration (C) of a substance and the
      length of time (t) it is administered produces a fixed level of effect for a
      given endpoint has been ascribed to Fritz Haber, who was a German scientist in
      the early 1900s. He contended that the acute lethality of war gases could be
      assessed by the amount of the gas in a cubic meter of air (i.e. the
      concentration) multiplied by the time in min that the animal had to breathe the
      air before death ensued (i.e. C x t=k). While Haber recognized that C x t=k was
      applicable only under certain conditions, many toxicologists have used his rule
      to analyze experimental data whether or not their chemicals, biological
      endpoints, and exposure scenarios were suitable candidates for the rule. The fact
      that the relationship between C and t is linear on a log-log scale and could
      easily be solved by hand, led to early acceptance among toxicologists,
      particularly in the field of entomology. In 1940, a statistician named Bliss
      provided an elegant treatment on the relationships among exposure time,
      concentration, and the toxicity of insecticides. He proposed solutions for when
      the log-log plot of C and t was composed of two or more rectilinear segments, for
      when the log-log plot was curvilinear, and for when the slope of the dosage
      mortality curve was a function of C. Despite the fact that Haber's rule can
      underestimate or overestimate effects (and consequently risks), it has been used
      in various settings by regulatory bodies. Examples are presented from the
      literature of data sets that follow Haber's rule as well as those that do not.
      Haber's rule is put into perspective by showing that it is simply a special case
      in a family of power law curves relating concentration and duration of exposure
      to a fixed level of response for a given endpoint. Also shown is how this power
      law family can be used to examine the three-dimensional surface relating C, t,
      and varying levels of response. The time has come to move beyond the limited view
      of C and t relationships inferred by Haber's rule to the use of the broader
      family of curves of which this rule is a special case.

PMID- 10963859
TI  - The role of time in toxicology or Haber's c x t product.
AB  - It happened exactly 100 years ago that Warren established for the first time a
      quantitative link between dose and time while studying the toxicity of sodium
      chloride in Daphnia magna (Straus). During this century many toxicologists in
      different contexts returned to this idea, which has become known as Haber's rule
      of inhalation toxicology. Most attempts to explore this relationship ended in
      frustration because of the supposed occurrence of exceptions. Thus, toxicologists
      concentrated on the quantitative relationship between dose and effect under
      mostly isotemporal conditions while time took a back seat and was assigned such
      arbitrary, semiquantitative designations as acute, subacute, subchronic and
      chronic. Time itself as a quantifiable variable of toxicity was seldom studied
      and when it was studied, it was often not under isodosic (steady state)
      conditions as required by theory. A recent analysis of toxicological time
      indicated the impact of three independent time scales (toxicokinetic,
      toxicodynamic, exposure frequency/duration) in toxicological studies, which
      interact with dose and effect to yield the enormous complexity known to every
      toxicologist. Based on prototypical examples when toxicokinetic (dioxins),
      toxicodynamic (nitrosamines, benzene) or exposure frequency (methylene chloride,
      chloroacetic acid, HgCl(2), CdCl(2), etc.) represent the critical time scale, the
      general validity of the c x t=k concept will be discussed as a starting point for
      a theory of toxicology. As endpoints of toxicity, (delayed) acute toxicity, blood
      dyscrasias and cancer will be used to illustrate the critical conditions needed
      to demonstrate the validity of this theory.

PMID- 10963860
TI  - The Haber-Weiss reaction and mechanisms of toxicity.
AB  - The concept that the highly reactive hydroxyl radical (HO) could be generated
      from an interaction between superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2))
      was proposed (with Joseph Weiss) in Professor Haber's final paper published in
      1934. Until it was recognized that free radicals are produced in biological
      systems, this finding seemed to have no relevance to biology. However, following
      the discovery that O(2)(-) was a normal cellular metabolite, it was quickly
      recognized that the Haber-Weiss reaction (O(2)(-)+H(2)O(2) -->HO+O(2)+HO(-))
      might provide a means to generate more toxic radicals. Although the basic
      reaction has a second order rate constant of zero in aqueous solution and thus
      cannot occur in biological systems, the ability of iron salts to serve as
      catalysts was discussed by these authors. Because transition metal ions,
      particularly iron, are present at low levels in biological systems, this pathway
      (commonly referred to as the iron-catalyzed Haber-Weiss reaction) has been widely
      postulated to account for the in vivo generation of the highly reactive HO.
      Recent data documenting the importance of redox regulation of various cellular
      signaling pathways makes it clear that free radicals are essential for normal
      cellular function. However, this also makes it obvious that disruptions of free
      radical production or defenses at many different levels can lead to adverse
      effects on cells. While the generation of HO, which is by far the most reactive
      oxygen species, is generally indicative of an overtly toxic event, it is through
      studies at this level that we have reached a better understanding of free
      radicals as both signaling molecules and toxic species.

PMID- 10963861
TI  - Natural language from function dynamics.
AB  - A new approach to syntax and semantics of language is presented as a form of
      function dynamics, which is studied both analytically and numerically. The
      iteration of the function dynamics leads to articulation and formation of rules,
      which depend on each other. A hierarchy of meta-rules as rules of rules also
      emerges through the iteration when the initial function is suitably embedded.
      Iteration of a model with dialogue between two function dynamics is shown to
      generate a higher level structure.

PMID- 10963862
TI  - Cryptography with DNA binary strands.
AB  - Biotechnological methods can be used for cryptography. Here two different
      cryptographic approaches based on DNA binary strands are shown. The first
      approach shows how DNA binary strands can be used for steganography, a technique
      of encryption by information hiding, to provide rapid encryption and decryption.
      It is shown that DNA steganography based on DNA binary strands is secure under
      the assumption that an interceptor has the same technological capabilities as
      sender and receiver of encrypted messages. The second approach shown here is
      based on steganography and a method of graphical subtraction of binary gel
      images. It can be used to constitute a molecular checksum and can be combined
      with the first approach to support encryption. DNA cryptography might become of
      practical relevance in the context of labelling organic and inorganic materials
      with DNA 'barcodes'.

PMID- 10963863
TI  - Data differentiation and parameter analysis of a chronic hepatitis B database
      with an artificial neuromolecular system.
AB  - This paper describes the application of a biologically motivated system to the
      diagnosis of chronic hepatitis B. The system integrates intra- and inter-neuronal
      information processing so as to capture the biology-like gradual transformability
      of structure/function relationships. The system was applied to a clinical
      hepatitis B database, divided into two sets. The first set comprised 676 records,
      of which one half were chronic hepatitis B patients, and the other half healthy
      individuals. The second set included 375 records, of which one third were chronic
      hepatitis B patients; another third were hepatitis B carriers, and the remaining
      third healthy non-carriers. Each record consisted of ten examination items.
      Experimental results showed that the system was able to correctly differentiate
      99.3 and 91.2% of the records in the first and the second sets, respectively.
      Differentiation means making a distinction between different categories of data
      in each set. After substantial learning with the first set, the system was then
      tested with the second set, and it was able to correctly differentiate 95. 7% of
      the records, suggesting a high differentiating capability in this system. This
      system demonstrated an effective self-organizing capability in determining
      significant and insignificant examination items from patterns of the clinical
      data. It also showed that some combinations of these items were more effective
      for determining whether one is infected with chronic hepatitis B than others.

PMID- 10963864
TI  - Minimizing stochastic complexity using local search and GLA with applications to
      classification of bacteria.
AB  - In this paper, we compare the performance of two iterative clustering methods
      when applied to an extensive data set describing strains of the bacterial family
      Enterobacteriaceae. In both methods, the classification (i.e. the number of
      classes and the partitioning) is determined by minimizing stochastic complexity.
      The first method performs the minimization by repeated application of the
      generalized Lloyd algorithm (GLA). The second method uses an optimization
      technique known as local search (LS). The method modifies the current solution by
      making global changes to the class structure and it, then, performs local fine
      tuning to find a local optimum. It is observed that if we fix the number of
      classes, the LS finds a classification with a lower stochastic complexity value
      than GLA. In addition, the variance of the solutions is much smaller for the LS
      due to its more systematic method of searching. Overall, the two algorithms
      produce similar classifications but they merge certain natural classes with
      microbiological relevance in different ways.

PMID- 10963865
TI  - From external to internal measurement: a form theory approach to evolution.
AB  - The point of view of external observers has led to an explanation of life based
      on digitally encoded information. In contrast, the existence of natural internal
      observers, or agents that belong to the same scale of the observed objects,
      explains the appearance of form centered approaches. The main controversies in
      thermodynamics and evolution are due to the changes of perspective, so as to
      speak, if measurement is considered to be external or internal. Equilibrium
      theories developed for closed systems under ideal conditions are analogous to
      external measurements. On the other hand, morphogenetic perspectives as far from
      equilibrium thermodynamics applicable to open systems allow to imagine self
      organizing agents that perform local measurements. Chaitin's algorithmic approach
      would help to elucidate the relation between digitally encoded information and
      active forms, because forms and shapes are responsible for specific pattern
      recognition and play a major role in the process of finding the proper measuring
      standard. The predominance of form over digital records is illustrated by
      studying the mapping between genetic descriptions and functional shapes,
      originally suggested for RNA, by Schuster. Therefore, interactions between living
      entities are seen as reciprocal measurement processes that bring about couplings
      (shortened descriptions and local decreases of entropy) that are paid by partial
      record erasure (increase of entropy). To conclude, this approach centered on the
      inner dynamics or form is appropriate for understanding how Lamarckism and the
      modern neutral theory of evolution can be integrated for expanding the
      neoDarwinian perspective.

PMID- 10963866
TI  - International Workshop on Early Folliculogenesis and Oocyte Development: Basic
      Clinical Aspects. London, United Kingdom, 10-11 June 1999. Proceedings and
      abstracts.

PMID- 10963867
TI  - Germ and somatic cell lineages in the developing gonad.
AB  - The germ cell lineage in the mouse becomes lineage-restricted about 7.2 days post
      coitum. Its progenitors have migrated from the proximal region of the epiblast,
      where they were subject to a predisposing signal from the adjacent extra
      embryonic ectoderm. It appears that this and other signals determine the
      emergence of germ cells: unlike in some other organisms, this event is not pre
      determined. After about 24 h in their initial extraembryonic location, the
      primordial germ cells migrate back into the embryo and make their way into the
      region of the developing gonad. Less is known about the origin of the various
      somatic cell lineages in the gonad, but some are known to derive from cells that
      migrate in from the mesonephros and others from the coelomic epithelium. Within
      the developing gonad, numerous interactions occur between the germ and somatic
      cell lineages. These are particularly important for the establishment of the
      spermatogenic lineage in the testis and for the differentiation of somatic tissue
      in the ovary. This paper will describe first the development of the germ cell
      lineage, up until about the time of birth, then the various somatic components of
      the gonad and finally the interactions that are known to occur between lineages.
      Unless otherwise stated, all the information refers to the mouse.

PMID- 10963868
TI  - Growth and paracrine factors regulating follicular formation and cellular
      function.
AB  - The purpose of this paper is to review, using fetal sheep as the animal model,
      aspects of ovarian development related to follicular formation and to report on
      the identity of growth and paracrine factors which might be involved in this
      process. Before follicular formation there is a massive and sustained
      colonisation of the fetal ovary by mesonephric cells, which become a precursor
      source of follicular cells. From within the ovarian medulla, somatic 'cell
      streams' branch into the cortex around nests of oogonia and oocytes. These 'cell
      streams', which contain elongated cells with either flattened or cuboidal shaped
      nuclei, express steroidogenic factor-1 (SF-1), steroid acute regulatory protein
      (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450(scc), and
      P450(aromatase) mRNA and/or protein. Follicles form from the association of an
      oocyte with the 'cell-stream' with either a single layer of flattened cells (i.e.
      type 1 follicle) or with a mixture of flattened and cuboidal cells (i.e. type 1a
      follicle). These newly-formed follicles have between 3 and 57 somatic cells (i.e.
      granulosa cells) and contain oocytes which vary in diameter between 23 and 52
      microm. Newly formed and early growing follicles have been identified with growth
      factors or growth factor receptors in either the oocytes or granulosa cells. Many
      of the growth factors are from the TGFbeta superfamily and are expressed in a
      cell- and stage-specific manner.

PMID- 10963869
TI  - The mouse zona pellucida: folliculogenesis, fertility and pre-implantation
      development.
AB  - Perinatally, oocytes within the mouse ovary become surrounded by a layer of
      flattened granulosa cells and form primordial follicles. The subsequent accretion
      of the zona pellucida between the oocytes and granulosa cells provides a
      biochemical marker of folliculogenesis. In mice, the zona matrix is composed of
      three proteins (ZP1, ZP2, ZP3). Mouse lines lacking either ZP1 or ZP3 have been
      established and have abnormal folliculogenesis. Without ZP1, structurally
      defective zonae are formed resulting in decreased fecundity due to early
      embryonic loss. More strikingly, without ZP3, the zona matrix is absent, no 2
      cell embryos are formed and females are infertile. The structural integrity of
      the zona matrix can be restored by substituting human homologues for the missing
      mouse protein and these 'humanized' zona matrices should prove useful in
      investigating the molecular basis of fertilization.

PMID- 10963870
TI  - Steroidogenic factor 1 (SF-1) is essential for ovarian development and function.
AB  - The orphan nuclear receptor steroidogenic factor 1 (SF-1) was identified
      originally as a key regulator of the tissue-specific expression of the cytochrome
      P450 steroid hydroxylases. Hints at considerably broader roles for SF-1 came from
      analyses of its expression pattern in mouse embryos. As anticipated, SF-1 was
      expressed in the adrenal glands and gonads from their early stages of
      development. Surprisingly, SF-1 also was expressed outside of the primary
      steroidogenic tissues in the anterior pituitary and hypothalamus. SF-1 knockout
      mice dramatically confirmed its multiple essential roles in vivo. These mice
      lacked adrenal glands and gonads, leading to adrenocortical insufficiency and
      male-to-female sex reversal of their internal and external genitalia. SF-1
      knockout mice also had impaired pituitary expression of gonadotropins and
      agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles of SF-1
      at all three levels of the hypothalamic-pituitary-gonadal axis. With some focus
      on the ovary, this review summarizes experiments that have defined essential
      roles of SF-1 in endocrine development, and highlights important areas for future
      studies.

PMID- 10963871
TI  - Morphologic and functional determinants of primordial and primary follicles in
      the monkey ovary.
AB  - In mammals, the mechanisms triggering initiation of follicular growth remain
      largely unknown. The present study constitutes an attempt to relate morphological
      and functional changes occuring in follicles at the time of transition from the
      nongrowing to the early growing stage. The population of very small follicles,
      including both nongrowing and early growing follicles, has been studied in fetal
      and adult monkey (Macaca fascicularis). Counts of these follicles and
      immunohistochemical analyses of their content in various intraovarian peptides
      led to the conclusion that initiation is probably not similar, on a quantitative
      as well as a qualitative point of view, in the fetal and in the adult ovary. In
      addition to the recently evidenced stimulatory role of the stem cell factor (SCF)
      in rats, activation of a nongrowing follicle might imply an arrest in the
      production of inhibiting factors, such as the transforming growth factor-beta2
      (TGF-beta2), occurring simultaneously with the production of stimulatory factors,
      such as the transforming growth factor-alpha (TGFalpha).

PMID- 10963872
TI  - Follicle dynamics during ovarian ageing.
AB  - The human ovary is endowed at birth with a fixed number of primordial follicles
      which steadily declines throughout life as a result of atresia and recruitment
      towards ovulation. The pattern of this decline is not exponential, but more bi
      exponential corresponding to a 'broken-stick' regression of logged total numbers
      of follicles against age. Such a model implies an abrupt change in the
      exponential rate of follicle loss at age 38 years, and is thus rather implausible
      biologically. A more refined model with an exponential rate of follicle loss that
      changes gradually throughout life also describes the data on declining follicle
      numbers but in addition leads to a distribution of age at menopause,
      corresponding to follicle numbers falling below a critical threshold, that shows
      quite remarkable agreement with independent data on menopausal ages of American
      women. When the follicles are classified into resting and growing stages, it is
      found that any changes in the consequent process of follicle development as the
      ovary ages relate mainly to the small resting follicles and not the larger
      growing ones.

PMID- 10963873
TI  - Follicular dynamics in the polycystic ovary syndrome.
AB  - Anovulation in women with polycystic ovary syndrome (PCOS) is characterised by
      arrested growth of antral follicles. A relative lack of FSH may contribute to the
      persistence of anovulation but is unlikely, by itself, to be a major cause of it.
      Granulosa cells from anovulatory women with polycystic ovaries hypersecrete
      oestradiol, compared with size-matched follicles from normal ovaries or
      polycystic ovaries from ovulatory women. This phenomenon appears to reflect a
      condition of advanced maturation of medium-sized antral follicles. The underlying
      basis for the abnormalities in anovulatory PCOS remains uncertain, but it is
      possible that there are intrinsic differences in folliculogenesis between
      polycystic and normal ovaries which affect preantral as well as antral follicles.
      An alternative - but not mutually exclusive - explanation of this disorder is the
      abnormal endocrine environment. Hypersecretion of both LH and insulin are typical
      of anovulatory women with PCOS. Studies in isolated granulosa cells, have shown,
      that insulin greatly augments the action of LH on steroidogenesis but this
      interaction may compromise further growth of medium-sized antral follicles by
      generation of 'preovulatory' concentrations of cAMP within the granulosa cell and
      thereby leading, prematurely, to terminal differentiation of granulosa cells.

PMID- 10963874
TI  - The primordial to primary follicle transition.
AB  - The mechanisms that regulate the gradual exit of ovarian follicles from the non
      growing, primordial pool are very poorly understood. A better understanding of
      the signals that initiate follicular growth in mammals, and of the conditions
      necessary for sustained growth of early preantral follicles in vitro, could have
      practical implications for contraception, alleviation of infertility, and
      regulation of the rate of follicle depletion (menopause). Our laboratory has
      developed two experimental systems that can be used to study factors involved in
      the activation of primordial follicles. In the first experimental system, small
      pieces of ovarian cortex, containing mostly primordial follicles, are isolated
      from fetal ovaries of cattle or baboons and cultured in serum-free medium. Under
      these conditions most primordial follicles become activated between 12 and 24 h
      of culture; their granulosa cells change shape, from flattened to cuboidal, and
      begin to express proliferating cell nuclear antigen (PCNA). During 7 days in
      culture, the newly-formed primary follicles and their oocytes increase
      significantly in diameter. This wholesale 'spontaneous' activation in serum-free
      medium is quite different from the much more gradual exit of primordial follicles
      from the resting pool that occurs in vivo and suggests that primordial follicles
      in vivo may be subject to a tonic inhibition of growth initiation or,
      alternatively, that some aspect(s) of the environment in vitro stimulates growth
      initiation. Recently we developed a second experimental system for studying
      activation of primordial follicles. Pieces of ovarian cortex from bovine or
      baboon fetuses were grafted beneath the developing chorioallantoic membrane (CAM)
      of 6-day-old chick embryos, a site known to support xenografted tissues. The
      cortical pieces were rapidly vascularized and histological analysis of pieces
      recovered after 2, 4, 7, or 10 days 'in ovo' revealed no increase in the number
      of primary follicles and maintenance of original numbers of primordial follicles.
      Therefore, grafting ovarian cortical pieces beneath the chick CAM provides an
      experimental system in which follicles remain at the primordial stage in a
      readily accessible environment and which, thus, may be used to study potential
      regulators of the initiation of follicle growth. The results suggest that
      vascularization of isolated pieces of ovarian cortex provides conditions that
      maintain follicular quiescence, whereas culture in vitro allows unrestrained
      activation of primordial follicles. Future studies with and comparisons of the in
      vitro and in ovo models may provide new insight into the mechanisms that regulate
      the primordial to primary follicle transition.

PMID- 10963875
TI  - Revelations of ovarian follicle biology from gene knockout mice.
AB  - Autocrine, paracrine and endocrine factors are necessary for normal ovarian
      folliculogenesis. A number of studies have demonstrated that the pituitary
      hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH) as well
      as granulosa cell-derived growth factors such as activins, inhibins, and kit
      ligand are necessary for follicle development. Recent knockout studies from our
      laboratory have demonstrated that mice lacking the pituitary proteins FSHbeta and
      activin receptor type II are infertile due to blocks at the pre-antral and antral
      follicle stages, respectively. Although the somatic cells of the ovary (the
      granulosa and theca cells) have long been implicated in ovarian function, only
      recently have we shown that the oocyte plays an essential role in controlling its
      own fate by influencing somatic cell functions. Mice lacking the oocyte-secreted
      growth factor, growth differentiation factor-9 (GDF-9), are infertile due to a
      block at the one-layer primary follicle stage, leading to secondary defects in
      thecal cell layer formation, oocyte growth and meiotic competence, and granulosa
      cell differentiation. Furthermore, using recombinant GDF-9, we demonstrate that
      GDF-9 also regulates cumulus expansion and expression of several key granulosa
      cell-specific genes. Thus, GDF-9 functions as an oocyte-secreted growth and
      differentiation factor during early and late folliculogenesis and at ovulation to
      regulate several key somatic cell functions essential for female reproduction.

PMID- 10963876
TI  - Neurotrophic and cell-cell dependent control of early follicular development.
AB  - Neurotrophins (NTs) and their receptors play an essential role in the
      differentiation and survival of defined neuronal populations of the central and
      peripheral nervous systems. Their actions, however, do not appear to be limited
      to the nervous system, as both NTs and their receptors have been found in non
      neuronal cells, including cells of the endocrine system. At least four of the
      five known neurotrophins, including nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and
      their receptors (p75 NTR, trkA, trkB and trkC) are present in the developing
      ovary. Using mice carrying null mutations of the genes encoding neurotrophins
      (NGF, NT-4, BDNF) or the receptor that mediates the actions of NT-4 and BDNF
      (trkB), we have obtained initial results consistent with the notion that
      neurotrophins are required for the growth of primordial follicles. NGF-deficient
      mice show a decreased formation of both primary and secondary preantral
      follicles. Null mutation of the NT-4 gene failed to affect either
      folliculogenesis or follicular development. However, formation of primary and
      secondary follicles was compromised in mice carrying a null mutation of both the
      NT-4 and BDNF genes, suggesting compensation of function by BDNF in NT-4
      knockouts. Support for this concept is provided by the similar deficiency in
      follicular growth observed in animals carrying a null mutation of the gene
      encoding trkB, the receptors mediating NT-4 and BDNF actions. Initial
      experiments, using differential display, to isolate genes that may be involved in
      the process of folliculogenesis and/or early follicular development, resulted in
      the isolation of a recently identified cell adhesion molecule and a novel
      transcription factor originally shown to induce cell transformation. It thus
      appears that formation and development of mammalian follicles requires the
      concerted action of genes originally thought to be only involved in cell
      differentiation/survival of neuronal cells, and genes that may control the
      growth, differentiation, and cell-cell interactions of somatic and germ cells in
      the ovary.

PMID- 10963877
TI  - Extracellular matrix in ovarian follicles.
AB  - A lot is known about the control of the development of ovarian follicles by
      growth factors and hormones, but less is known about the roles of extracellular
      matrix in the control of follicular growth and development. In this review we
      focus on the specialized extracellular matrix of the basal laminas that are
      present in ovarian follicles. These include the follicular basal lamina itself,
      the Call-Exner bodies of the membrana granulosa, the subendothelial and arteriole
      smooth muscle basal laminas in the theca, and the basal lamina-like material of
      the thecal matrix. We discuss the evidence that during follicle development the
      follicular basal lamina changes in composition, that many of its components are
      produced by the granulosa cells, and that the follicular basal laminas of
      different follicles have different ultrastructural appearances, linked to the
      shape of the aligning granulosa cells. All these studies suggest that the
      follicular basal lamina is extremely dynamic during follicular development.

PMID- 10963878
TI  - The roles of activins, inhibins and estrogen in early committed follicles.
AB  - The hypothesis that activin and inhibin are autocrine/paracrine mediators of
      ovarian folliculogenesis has a solid basis. In mouse and rat models, granulosa
      cells (GC) of committed follicles express mRNA and protein for the
      activin/inhibin subunits and mRNA for the activin receptors (type I and II).
      Dimeric inhibin-A and -B are produced by postnatal ovarian cell dispersates and
      (GC) in culture. Similar levels of inhibin-A and -B are produced by postnatal
      ovarian cells, but thereafter as the ovary develops, inhibin-A becomes the
      predominant form. Activin was more effective than transforming growth factor-beta
      (TGF-beta) in enhancing follicle stimulating hormone (FSH)-stimulated inhibin
      production by ovarian cells. Evidence for a local regulatory role of estrogen in
      the ovary is also accumulating. Murine models of estrogen receptor (ERalpha or
      ERbeta) disruption produce mice with abnormal ovarian phenotypes. Female mice,
      which lack the capacity to produce estrogen (ArKO mice), have arrested
      folliculogenesis, no corpora lutea, elevated levels of luteinising hormone (LH),
      FSH and testosterone and are infertile. These data are consistent with
      autocrine/paracrine actions of activin in the early growth of committed follicles
      and estrogen in follicular maturation.

PMID- 10963879
TI  - Importance of the IGF system in early folliculogenesis.
AB  - In the primate ovary, androgens promote oocyte insulin-like growth factor (IGF) I
      expression as well as initiation of follicle development. In most other mammals,
      IGFs do not appear to be required for the entry of follicles into the pool of
      growing follicles and for their gonadotropin-independent development. In
      contrast, IGFs are involved in the increase in FSH-responsiveness of granulosa
      cells when follicles enter into the gonadotropin-dependent stages of follicular
      development (200 microm in mouse, 2 mm in sheep, 5 mm diameter in cattle). In the
      late stages of folliculogenesis, the decrease in IGFBPs participates in the
      increase in IGF bioavailability, leading to a further amplification of FSH
      action.

PMID- 10963881
TI  - Oocyte attrition.
AB  - During oogenesis, germ cell numbers sharply decrease when meiosis is initiated.
      There is solid evidence (DNA ladders, in situ detection) that this loss is
      through apoptosis. Oocyte apoptosis appears to hit mitotic primordial germ cells
      (PGC), pachytene oocytes and early primordial follicles. The control of oocyte
      apoptosis is not fully understood, although survival factors (LIF, kit ligand and
      FGF), as well as death inducing factors (fas ligand, TGFbeta), have been
      identified. Fas ligand binding on oocytic fas may result in caspase 8 activation.
      Two pathways inducing oocyte apoptosis may then be operating. In the first one,
      activated caspase 8 will induce activation of executioner caspases. In the second
      one, activated caspase 8 will trigger the cleavage of the bcl(2) family member
      Bid, which will act on mitochondria, resulting in cytochrome c release, caspase 9
      activation and finally, activation of all executioner caspases. As a consequence
      of caspase activation, alterations in the cell nucleus (DNAse activation, PARP
      fragmentation), in the cell cytoskeleton (lamin) and cell metabolism will occur,
      producing cell death. During folliculogenesis, germ cell loss, owing to oocyte
      apoptosis, has been postulated within primordial and preantral follicles. Its
      regulatory mechanisms may be even more complex than those operating in foetal
      oocytes since additional control factors include EGF/TGFalpha and bcl(2)
      (survival) and activin (death inducer). In contrast, oocytes from antral
      follicles appear to be very unsensitive to death inducing stimuli.

PMID- 10963880
TI  - Hormonal regulation of early follicle development in the rat ovary.
AB  - Although earlier studies focused on the hormonal regulation of antral and
      preovulatory follicles, recent studies indicate the importance of the hormonal
      control mechanism for preantral follicles. The endocrine hormone FSH is not only
      a survival factor for early antral follicles but also a potent growth and
      differentiation factor for preantral follicles. In addition, KGF secreted by
      theca cells and c-kit ligand secreted by granulosa cells play paracrine roles in
      the regulation of preantral follicle growth and development. Furthermore oocyte
      derived GDF-9 promotes the growth and differentiation of early follicles by
      acting on somatic cells in the follicle. It is likely that the genetic makeup of
      an oocyte could determine the secretion of oocyte hormones which would, in turn,
      regulate the growth and differentiation of the surrounding somatic cells of that
      follicle. A better understanding of the hormonal mechanisms underlying early
      follicle development could provide a refined culture system for the in vitro
      maturation of fertilizable oocytes and future design of fertility and
      contraceptive agents.

PMID- 10963882
TI  - Conditions that affect acquisition of developmental competence by mouse oocytes
      in vitro: FSH, insulin, glucose and ascorbic acid.
AB  - The simplest unit required for the support of oocyte growth and development is
      the oocyte-granulosa cell complex. Therefore, a culture system was established
      that utilizes these complexes to assess mechanisms promoting nuclear, cytoplasmic
      and genomic maturation in mammalian oocytes. Deletion of serum from the culture,
      results in increased apoptosis in oocyte-associated granulosa cells (OAGCs),
      however, addition of ascorbic acid (0.5 mM) significantly reduced the level of
      apoptosis in the OAGCs, although no improvement of oocyte developmental
      competence was detected. The effects of reducing glucose during oocyte growth
      were studied since, under some culture conditions, glucose has deleterious
      effects on early preimplantation development. Reducing the glucose concentration
      to 1 mM resulted in the production of oocytes with greatly reduced developmental
      competence. Deleterious effects of FSH plus insulin during oocyte growth in vitro
      on preimplantation development are reviewed and discussed in terms of the
      communication of oocytes with inappropriately developing granulosa cells.
      Evidence that oocytes promote the appropriate differentiation of OAGCs in intact
      follicles in vivo is also discussed. It is hypothesized that oocytes control the
      differentiation of these cells, in order to promote intercellular signaling
      essential for the acquisition of competence to undergo normal embryogenesis.

PMID- 10963883
TI  - In vitro development of oocytes from porcine and bovine primary follicles.
AB  - A limiting factor to realising the full potential of many of the new reproductive
      techniques is the lack of availability of fertile oocytes. Methods for maturing
      oocytes in vitro (IVM) have been developed to address this problem but the
      success rate and quality of embryos produced by IVM is variable. The variation in
      success may be due to the poor quality of oocytes that are being selected for
      maturation, since these would be taken from developed antral follicles. To
      attempt to eliminate this variation and increase the numbers produced, it may be
      better to use the large source of oocytes from preantral and primordial follicles
      by developing systems for in vitro growth (IVG). In vitro systems that utilise
      early growing follicles as a source of oocytes have been developed for laboratory
      species and these have been successful in producing live young. If successful,
      IVG in association with IVM would supercede existing technology for assisted
      reproduction in both humans and animals by making it possible to develop the
      desired number of high quality oocytes from small amounts of ovarian tissue.
      However, developing IVG systems for species with follicles that develop over
      several months presents enormous technical challenges. We have developed systems
      that permit the growth of individual porcine and bovine preantral follicles for
      periods of up to 20 days. Porcine follicles grown in micro-wells show a higher
      rate of survival if grown in the presence of serum than follicles grown under
      serum free conditions. Oocytes recovered from in vitro grown porcine follicles
      are capable of reaching metaphase II after in vitro maturation. A similar system
      has been developed for bovine follicles and survival rate is high under serum
      free conditions but as yet no oocytes from in vitro grown oocytes have been
      capable of completing meiotic maturation.

PMID- 10963885
TI  - Ovarian autografts in sheep as a model for studying folliculogenesis.
AB  - The studies outlined in this review indicate that the cortical autograft, in
      addition to its clinical application as a means to restore fertility, represents
      a valuable experimental model that can be exploited to examine aspects of both
      early and terminal follicle development. The autograft procedure is a means to
      experimentally deplete the follicle population in an individual and this
      procedure results in similar endocrine changes and reproductive cycle
      perturbances as those observed in aged sheep and women with incipient ovarian
      failure. This methodology therefore represents a non-primate large animal model
      to study the consequences of, and possible interventions to overcome,
      reproductive problems associated with depleted ovarian follicular reserves.
      Without the necessity of keeping animals for large periods of time so that this
      depletion can occur naturally. In terms of early follicle development, the fact
      that the ischaemia that occurs during revascularisation of the autograft
      effectively synchronises follicle development at the primordial stages of
      development means that the autograft can be used as a model to study the control
      of early follicle development. This model has been used to examine the role of
      FSH (follicle stimulating hormone) in the control of early follicle development
      and the preliminary data presented provides strong evidence that FSH does indeed
      modulate early folliculogenesis, confirming the value of this model as a means of
      performing experimental investigations in this area. Further work using this
      model will concentrate on the role of other endocrine and local factors in the
      control of early folliculogenesis and the identification of the key developmental
      checkpoints during this process, with a view to designing physiological culture
      systems to support early follicle and oocyte development.

PMID- 10963884
TI  - Low temperature storage and grafting of human ovarian tissue.
AB  - A finite stockpile of germ cells forms in the human ovary before birth and is
      progressively utilised until it is almost exhausted at menopause in mid-life.
      Currently, there is no proven method for preventing wastage of this irreplaceable
      store, although cryopreservation provides an opportunity for long-term
      preservation of oocytes. This technology can potentially be used to conserve
      fertility in patients undergoing sterilising treatment or otherwise at risk of an
      early menopause. The structure of the ovary is well-suited to tissue storage
      because primordial follicles are abundant, developmentally dormant and located
      peripherally. Thin cortical slices of tissue can be prepared either from biopsies
      collected laparoscopically or by dissecting the cortex from the whole ovary. To
      test survival after freezing and thawing, tissues donated from women undergoing
      Caesarian section or gynaecological surgery were cooled slowly to liquid nitrogen
      temperatures in various cryoprotectant solutions and thawed rapidly. Three weeks
      after grafting under the renal capsule of immunodeficient SCID mice the majority
      of follicles were still viable. To test the procedure in human volunteers, small
      discs of ovarian tissue were autografted to the anterior uterus. After 3-4 months
      the tissues still contained follicles, including growing stages with PCNA
      positive granulosa cells, but only about a quarter of the original follicle
      population had survived. In another study using either human xenografts or murine
      isografts, follicle survival rates were improved by administration of
      antioxidants to counteract ischaemia-reperfusion injury. Ovarian tissue banking
      should still be regarded as an experimental procedure, though recent results
      indicate that it has clinical potential.

PMID- 10963886
TI  - Gonadotrophin administration can benefit ovarian tissue grafted to the body wall:
      implications for human ovarian grafting.
AB  - Ovarian grafting provides a strategy for clinical infertility treatment and is
      starting to be used in conjunction with ovarian tissue storage for patients at
      risk of early ovarian failure. As patients are starting to return for their
      frozen stored tissue we need to ascertain how to maximise follicle survival when
      this tissue is grafted back to the patient. For research purposes ovarian tissue
      is commonly grafted to the kidney capsule as the rich capillary bed at this site
      favours rapid graft revascularization. This is however not an ideal site for
      natural conceptions or for the harvest of mature oocytes for in vitro
      fertilization. While oocytes would be relatively easy to recover from grafts on
      the abdominal wall or subcutaneous tissue graft revascularization at these sites
      is slower and evidence indicates that fewer follicles survive. As gonadotropins
      can upregulate angiogenic growth factors in the ovary this study was designed to
      test whether the administration of exogenous gonadotropins would increase the
      number of surviving follicles in grafts placed at less vascularised sites. We
      showed that exogenous gonadotrophins, given to either the donor or the recipient,
      could increase the number of developing follicles but the magnitude of this
      effect was influenced by the timing of the injections relative to the time of
      grafting.

PMID- 10963887
TI  - Muscle pain activates a direct projection from ventrolateral periaqueductal gray
      to rostral ventrolateral medulla in rats.
AB  - Activation of the ventrolateral periaqueductal gray (vlPAG) evokes a reaction of
      quiescence, immobility, hypotension and bradycardia. Pain of deep somatic or
      visceral origin also often triggers a reaction of quiescence, immobility,
      hypotension and bradycardia and further, evokes a selective increase in immediate
      early-gene (c-Fos) expression within the vlPAG. Vasodepression evoked from the
      vlPAG is thought to be mediated by an inhibition of presympathetic neurons within
      the rostral ventrolateral medulla (RVLM). In this study the prior injection of
      retrograde tracer into the RVLM was combined with the use of Fos expression as a
      marker of neuronal activation, to determine if deep (muscle) pain-evoked
      vasodepression could be mediated by a direct vlPAG-RVLM pathway. It was revealed
      that intramuscular injection of formalin, in the anaesthetised rat, evoked a
      significant increase in Fos expression within the caudal vlPAG, and that
      approximately 25% of the Fos-immunoreactive neurons projected to the RVLM.

PMID- 10963888
TI  - Intracerebroventricular administration of the beta(3)-adrenoceptor agonist CL
      316243 causes Fos immunoreactivity in discrete regions of rat hypothalamus.
AB  - Intracerebroventricular (i.c.v.) administration of the beta(3)-AR agonist
      BRL37344 causes dose dependent decreases in food intake in rats suggesting a role
      for beta(3)-AR in the central control of feeding. We have conducted experiments
      investigating the effects of i.c.v. administration of the selective beta(3)-AR
      agonist CL316243 on Fos expression to determine whether beta(3)-AR stimulation
      affects neurones within specific brain nuclei. Significantly higher numbers of
      Fos positive cells were found in the rats treated i.c.v. with CL316243 compared
      with control rats in the paraventricular hypothalamus, lateral hypothalamic area,
      ventromedial hypothalamic nucleus and dorsal hypothalamic area. Pre-treatment
      with the selective beta(3)-AR antagonist SR59230A resulted in a significant
      decrease in the number of Fos positive cells in all those areas compared with
      rats treated with CL316243 alone. These experiments demonstrate that i.c.v.
      administration of selective beta(3)-AR agonist causes neuronal activation in
      hypothalamic areas important in the central regulation of appetite via a beta(3)
      AR mediated effect.

PMID- 10963890
TI  - Glycogen is mobilized during the disposal of peroxides by cultured astroglial
      cells from rat brain.
AB  - Regeneration of reduced nicotinamide adenine dinucleotide phosphate (NADPH) is
      essential for the activity of glutathione redox cycling during cellular peroxide
      detoxification. In order to test for a function of astroglial glycogen to serve
      as endogenous precursor for glucose-6-phosphate, the substrate for the
      regeneration of NADPH by the pentose phosphate pathway, the content of glycogen
      in astroglia-rich primary cultures derived from the brains of newborn rats was
      determined after application of peroxides. In the presence of hydrogen peroxide
      or cumene hydroperoxide in concentrations of 200 microM glycogen was mobilized
      with a half-life of 16 min in incubation medium containing 20 mM glucose, whereas
      in the absence of peroxides the glycogen content decreased more slowly with a
      half-life of 42 min. After 30 min of incubation with or without peroxides 30 and
      73%, respectively, of the initial glycogen content was found. The degree of
      glycogen mobilization was reduced by lowering the initial concentration of the
      peroxides. These results demonstrate that in astroglial cells (i) glucosyl
      residues of glycogen are mobilized after application of peroxides despite the
      presence of exogenous glucose, and (ii) that the demand for glucose-6-phosphate
      as substrate for NADPH regeneration via the pentose phosphate pathway can, at
      least partially, be met by mobilization of glycogen.

PMID- 10963889
TI  - Adenosine triphosphate mobilizes cytosolic calcium and modulates ionic currents
      in mouse taste receptor cells.
AB  - By using photometry and the patch clamp technique, we identified P(2Y)-like
      receptors in mouse taste receptor cells (TRCs) and found them to be coupled to
      Ca(2+) mobilization and ionic current modulation. Particularly, adenosine
      triphosphate (ATP) and the P(2Y) agonist 2-methylthio-ATP increased intracellular
      Ca(2+) by stimulating the phosphoinositide pathway, whereas beta, gamma-methylene
      D-ATP, a P(2X) agonist, was ineffective. In a distinctive TRC subpopulation, ATP
      closed Ca(2+) channels. This regulation may underlie the negative feedback tuning
      neurotransmitter release. By mobilizing intracellular Ca(2+), ATP activated
      Ca(2+)-dependent Cl(-) channels, the intracellular event that may universally
      occur upon taste stimulation triggering IP(3) formation and Ca(2+) release in the
      TRC cytoplasm.

PMID- 10963891
TI  - Identification of phosphorylated form of cAMP/calcium response element binding
      protein expression in the brain stem nuclei at early stage of vestibular
      compensation in rats.
AB  - The present study was aimed at evaluating the time-dependent expressions of
      phosphorylated forms in the cAMP/calcium response element binding protein (pCREB)
      known to be one of transcription factors for immediate early genes in the brain
      stem nuclei of Sprague-Dalwey rats. Animals received surgical ablation of right
      peripheral vestibular labyrinth through a ventral approach. Immunohistochemical
      staining and digital image analysis systems were used to observe pCREB
      expressions in neuronal cells of the brain stem nuclei. The number of pCREB
      labeling neurons were increased with time, and peaked in the vestibular nuclear
      complex (VNC) bilaterally 1 h after unilateral labyrinthectomy (UL). In addition,
      high levels of phosphorylated CREB-like immunoreactivity (pCREB-LI) were also
      observed in bilateral cerebellum, olivary nuclear complex, and medullary nuclei.
      There was a rapid reduction of pCREB-LI in contralateral VNC but a slow reduction
      in the ipsilateral side 2 h after UL, causing an asymmetric number of pCREB
      labeling neurons between bilateral VNC (P<0.05). Thereafter pCREB-LI in bilateral
      VNC decreased to a very low level and returned to basal level 24 h after UL.
      These results suggest that the activation of the cAMP/calcium response element
      binding protein plays a role in the initial events of vestibular compensation in
      rats.

PMID- 10963892
TI  - Angiotensin I converting enzyme polymorphism in humans with age-associated memory
      impairment: relationship with cognitive performance.
AB  - We compared the distribution of an insertion (I)/deletion (D) polymorphism coding
      for the angiotensin I converting enzyme (ACE) gene in 100 subjects fulfilling
      NIMH criteria for Age-associated memory impairment (AAMI) and 124 controls. We
      found significantly reduced prevalences of the ACE I/I genotype together with
      increases of the ACE D allele in the AAMI group. We further compared the
      neuropsychological performance of the AAMI group according to their ACE genotype.
      Those AAMI subjects presenting the ACE I/I genotype exhibited better performance
      on a measure of frontal lobe function. Our results suggest that the lack of the
      ACE I/I genotype and the presence of the ACE D allele are associated with memory
      impairment in the elderly.

PMID- 10963893
TI  - The synchronization of human arm movements to external events.
AB  - Previous research revealed the existence of coupling mechanisms (e.g. iso
      directionality) at the level of perception and action. The present experiment
      investigated how the strength of the perception-action coupling affected
      synchronization performance. Arm movements were to be synchronized with a moving
      light that traveled back and forth from the left to the right side of a runway.
      Four experimental conditions were administered representing the orthogonal
      combination of two viewing conditions (intermittent vs. continuous) and two
      synchronization modes (in-phase, i.e. arm moving in the same direction as the
      light vs. anti-phase, i.e. arm moving in the opposite direction). Performance
      outcome measures, movement kinematics, and relative phase were used to examine
      the data. The results revealed a better synchronization performance when the arm
      and light traveled in the same direction (iso-directionality) during the
      continuous viewing condition. Apparently, the strength of the perception-action
      coupling has a severe impact on the quality of the synchronization of an arm
      movement to an external event.

PMID- 10963894
TI  - The endogenous survival promotion of axotomized rat corticospinal neurons by
      brain-derived neurotrophic factor is mediated via paracrine, rather than
      autocrine mechanisms.
AB  - The previously reported rescue of corticospinal neurons (CSN) from axotomy
      induced death by intracortical glial cell line-derived neurotrophic factor (GDNF)
      and neurotrophin-3 (NT-3)-infusions depends on endogenous cortical brain-derived
      neurotrophic factor (BDNF). The present study examines whether BDNF, GDNF, or NT
      3 can stimulate an autocrine or paracrine BDNF-support of lesioned CSN. BDNF
      infusions increase BDNF mRNA-expression throughout cortical layers 2-5 and NT-3
      treatment results in upregulation of BDNF-transcripts in the upper cortical
      layers. In contrast, GDNF-treatment had no effect. While virtually all CSN
      express the BDNF-receptor trkB, less than half of them express BDNF, and these
      expression patterns are unchanged after axotomy and the different neurotrophic
      factor treatments. The findings suggest that axotomized CSN are supported via a
      paracrine BDNF-mechanism which can be stimulated by BDNF- and NT-3-, but not by
      GDNF.

PMID- 10963895
TI  - Changes in phosphoinositide signalling activity and levels of the alpha subunit
      of G(q/11) protein in rat brain induced by E-5842, a sigma(1) receptor ligand and
      potential atypical antipsychotic.
AB  - Changes in the phosphoinositide (PPI) signal transduction system induced by E
      5842, a new sigma(1) (sigma(1)) receptor ligand and potential atypical
      antipsychotic, were studied in the rat frontal cortex, hippocampus and striatum.
      Acute treatment with E-5842 increased phospholipase C (PLC) activity in the
      striatum and the hippocampus. Chronic treatment with E-5842 induced an increase
      in the activity of PLC in the frontal cortex and the striatum. Similar up
      regulation of the activity of the enzyme was also observed in rat frontal cortex
      membranes in presence of GTPgammaS. After chronic treatment with E-5842, it was
      also observed a significant increase of the immunoreactivity levels of
      G(q/11)alpha in the frontal cortex. Our results suggest that part of the
      antipsychotic effects of E-5842 could be related to the regulation of the PPI
      signal transduction pathway, especially after a prolonged treatment.

PMID- 10963896
TI  - Evidence of the synthesis of opioid receptor like 1 receptor in nociceptinergic
      neurons in rat brain suggests the existence of autoreceptor: a confocal double
      staining study.
AB  - Opioid receptor like 1 (ORL1) receptor is a novel member of the opioid receptor
      family, which was not bound by any of the typical opioid receptor ligands but
      bound by the recently discovered nociceptin (also termed orphanin FQ) with high
      affinity. By using double staining of fluorescent in situ hybridization and
      immunohistochemistry, we observed the expression of ORL1 receptor mRNA in
      nociceptin-like immunoreactive neurons in multiple areas in rat brain including
      the hippocampus, arcuate nucleus in the hypothalamus, ventralateral
      periaquiductal gray (PAG) and raphe nuclei in brain stem. The expression of ORL1
      mRNA in nociceptinergic neurons suggests that these receptors mediate, at least
      in part, the presynaptic autoreceptor functions. Further anatomical and
      functional significance of the autoreceptor of nociceptinergic neurons remain to
      be elucidated.

PMID- 10963898
TI  - Protein kinase C activation by phorbol ester increases in vitro invasion through
      regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases
      system in D54 human glioblastoma cells.
AB  - To elucidate possible mechanisms of phorbol 12-myristate 13-acetate (PMA) induced
      in vitro invasiveness of glioblastoma cells, we examined expression levels of
      membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, MMP-9 and tissue
      inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 using Western blotting and
      gelatin zymography assay, and found that PMA induced the secretion of MMP-9,
      activated MMP-2 proenzyme to fully active form of 59 kDa, down-regulated the TIMP
      1 and TIMP-2 secretion, and increased MT1-MMP on the cell surface. However, PKC
      inhibitor Go 6983 reversed all of these effects brought about by PMA. We,
      therefore, conclude the activation of PKC by PMA in these cells plays a critical
      role in the regulation of MMPs/TIMPs system, which has a major role in tumor
      invasion and metastasis.

PMID- 10963897
TI  - Bis(7)-tacrine, a promising anti-Alzheimer's agent, reduces hydrogen peroxide
      induced injury in rat pheochromocytoma cells: comparison with tacrine.
AB  - The present study investigates the effects of bis(7)-tacrine, a novel dimeric
      acetylcholinesterase inhibitor, on hydrogen peroxide(H(2)O(2))-induced cell
      injury with comparison to the corresponding monomer, tacrine. Exposure of rat
      pheochromocytoma line PC12 cells to H(2)O(2) induced significant cell damage.
      This reagent also caused redox desequilibrium as indicated by a decrease in
      activities of intracellular antioxidant enzymes such as glutathione peroxidase as
      well as catalase and an accumulation of malondialdehyde, a product of lipid
      peroxidation. Pretreatment of cells with bis(7)-tacrine or tacrine attenuated
      H(2)O(2)-induced cell toxicity, and bis(7)-tacrine demonstrated higher potency
      than tacrine in improving redox desequilibrium. These results suggest that bis(7)
      tacrine and tacrine significantly protect against H(2)O(2) insult, which might be
      beneficial for their potential usage in the prevention and treatment of
      Alzheimer's disease.

PMID- 10963899
TI  - Photostimulation affects gonadotropin-releasing hormone immunoreactivity and
      activates a distinct neuron population in the hypothalamus of the mallard.
AB  - To reveal central mechanisms that transduce photic stimuli to sexually related
      neuroendocrine changes, Fra-2-ir, an inducible immediate-early gene marker of
      neuronal activation has been consecutively localized with that of GnRH-I in the
      brain of mallards that were triggered by artificial light at the photosensitive
      phase of the reproductive cycle. Strong neuronal activation was found in the POM
      and PVN in response to 1x or 4x 20 h light exposure that was accompanied with an
      increase of GnRH-ir in the hypothalamus and a dramatic depletion of GnRH-ir from
      terminals in the median eminence. The Fra-2 and GnRH-ir profiles, however, were
      not co-localized in any region at any phase of photostimulation. These results
      demonstrate profound changes of GnRH-ir in the hypothalamus and reveal a
      distinct, photoresponsive cell population in the anterior hypothalamic area of
      the mallard.

PMID- 10963900
TI  - Glufosinate ammonium stimulates nitric oxide production through N-methyl D
      aspartate receptors in rat cerebellum.
AB  - Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal
      ingredient. The neuronal activities of this compound were investigated by use of
      a microdialysis system that allowed us to measure nitric oxide production in the
      rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate
      (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10
      microliter), which were administered through the microdialysis probe at a rate of
      1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate
      ammonium-elicited increase in nitric oxide production was suppressed by an
      inhibitor of nitric oxide synthase and was antagonized by NMDA receptor
      antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptor antagonist. These results suggest that glufosinate
      ammonium stimulates nitric oxide production through NMDA receptors.

PMID- 10963901
TI  - Erythropoietin protects cultured cortical neurons, but not astroglia, from
      hypoxia and AMPA toxicity.
AB  - In addition to its better-known hemopoietic action, erythropoietin (Epo) has
      neurotrophic properties and neuroprotective effects in some models of hypoxic
      ischemic injury. To define further the cellular mechanisms underlying
      neuroprotection by Epo, we studied the effects of Epo on hypoxia with glucose
      deprivation in cultured rat cortical neurons and astroglia and on exposure to
      excitotoxins in cultured rat cortical neurons. Epo (30 pM) reduced neuronal, but
      not astroglial, cell death from hypoxia with glucose deprivation, and also
      attenuated the neurotoxic effect of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid (AMPA), but not other excitotoxins. Epo appears to protect
      against cerebral ischemia through a direct effect on neurons that may be mediated
      in part by AMPA receptors.

PMID- 10963902
TI  - Asymmetrical visual fields distribution of attention in dyslexic children: a
      neuropsychological study.
AB  - Visual spatial attention was evaluated in dyslexic and normally reading children
      by using a flanker task. When an irrelevant distractor is presented adjacent to a
      target stimulus, interference is observed when the two stimuli are associated
      with conflicting responses. In the present study the distractor flanked the
      target either to the right or to the left. Results showed an asymmetric flanker
      effect in dyslexics, whereas it was symmetrical in normal readers. Dyslexics
      exhibited a reduced flanker effect in the left visual field, concomitant with a
      strong flanker effect in the right visual field. These results give further
      support to the hypothesized left-side minineglect in dyslexics. Data also provide
      evidence for a reduced ability in suppressing distracting information in the
      right visual field. Such visual field asymmetry is thought to play a crucial role
      in reading disorders. Right over-distractibility and left inattention suggest an
      impairment of the right parietal functions as supported by the magnocellular
      theory of dyslexia.

PMID- 10963903
TI  - Dynorphin: friend or foe?

PMID- 10963904
TI  - Parabrachial area and nucleus raphe magnus inhibition of corneal units in rostral
      and caudal portions of trigeminal subnucleus caudalis in the rat.
AB  - The cornea has been used extensively as a means to selectively stimulate
      trigeminal nociceptive neurons. The aim of this study was to determine the
      effects of descending modulatory control pathways on corneal unit activity by
      comparing the effects of conditioning stimulation of the pontine parabrachial
      area (PBA CS) and nucleus raphe magnus (NRM CS). Electrical stimulation of the
      cornea at A- and C-fiber intensities was used to activate neurons in two regions
      of the trigeminal spinal nucleus, the subnucleus interpolaris/caudalis transition
      (Vi/Vc, 'rostral units') and laminae I-II at the subnucleus caudalis/cervical
      cord transition (Vc/C1, 'caudal units'), in chloralose-anesthetized rats. Corneal
      units were further classified according to convergent cutaneous receptive field
      properties and PBA projection status. None of 48 rostral and 23/28 caudal units
      projected to the ipsilateral or contralateral PBA. PBA CS inhibited the cornea
      evoked responses (<75% change from control) of approximately 65% of rostral and
      caudal units regardless of neuronal class. For rostral corneal units, PBA CS
      inhibited A- and C-fiber input equally (15+/-3 and 18+/-14% of control,
      respectively), whereas among caudal units, A-fiber input was inhibited more than
      C-fiber input (26+/-5 and 64+/-12% of control, respectively, P<0.01). The
      magnitude of NRM CS inhibition on cornea-evoked activity of both rostral and
      caudal units was not different from that seen after PBA CS. Glutamate
      microinjections into PBA also inhibited rostral and caudal corneal units (6/9
      tested). These results indicate that corneal input to rostral and caudal units is
      modified by activation of descending controls from the PBA and NRM. The
      significance for processing corneal sensory information is discussed in terms of
      functional differences between rostral and caudal neurons.

PMID- 10963906
TI  - Supraspinal cholecystokinin may drive tonic descending facilitation mechanisms to
      maintain neuropathic pain in the rat.
AB  - Complete or partial spinal section at T(8) has been shown to block tactile
      allodynia but not thermal hyperalgesia following L(5)/L(6) spinal nerve ligation
      (SNL), suggesting the supraspinal integration of allodynia in neuropathic pain.
      In the present study, the possibility of mediation of nerve injury-associated
      pain through tonic activity of descending nociceptive facilitation arising from
      the rostroventromedial medulla (RVM) was investigated. Specifically, the actions
      of brainstem cholecystokinin and the possible importance of sustained afferent
      input from injured nerve fibers were determined using pharmacological and
      physiological approaches in rats with SNL. Lidocaine given bilaterally into the
      RVM blocked tactile allodynia and thermal hyperalgesia in SNL rats and was
      inactive in sham-operated rats. Bilateral injection of L365,260 (CCK(B) receptor
      antagonist) into the RVM also reversed both tactile allodynia and thermal
      hyperalgesia. Microinjection of CCK-8 (s) into the RVM of naive rats produced a
      robust tactile allodynic effect and a more modest hyperalgesia. CCK
      immunoreactivity was not significantly different between SNL and sham-operated
      rats. The anti-nociceptive effect of morphine given into the ventrolateral
      periaqueductal gray region (PAG) was substantially reduced by SNL. The injection
      of L365,260 into the RVM or of bupivacaine at the site of nerve injury restored
      the potency and efficacy of PAG morphine in SNL rats. These results suggest that
      changes in supraspinal processing are likely to contribute to the observed poor
      efficacy of opioids in clinical states of neuropathic pain. These data also
      indicate that the activation of descending nociceptive facilitatory pathways is
      important in the maintenance of neuropathic pain, appears to be dependent on CCK
      release, and may be driven from sustained afferent input from injured nerves to
      brainstem sites. Collectively, these data support the hypothesis that abnormal
      tonic activity of descending facilitation mechanisms may underlie chronic pain
      from peripheral nerve injury.

PMID- 10963905
TI  - Oral anti-hyperalgesic and anti-inflammatory activity of NK(1) receptor
      antagonists in models of inflammatory hyperalgesia of the guinea-pig.
AB  - The oral analgesic and anti-inflammatory activity of NK(1) antagonists with
      species preference for the human receptor were assessed in (1) the carrageenan
      induced inflammatory hyperalgesia and (2) Freund's complete adjuvant (FCA)
      induced extravasation in the knee joint models of the guinea-pig, respectively.
      Mechanical hyperalgesia was determined by measuring the withdrawal threshold to a
      noxious mechanical stimulus applied to the paw and thermal hyperalgesia as the
      withdrawal latency to a noxious thermal stimulus applied to the plantar surface.
      A concentration of 1.0% carrageenan (intraplantar) reduced mechanical thresholds
      from 124+/-5 to 63+/-3 g and thermal latencies from 19+/-0.4 to 4.7+/-0.9 s as
      determined 4 h after injection. The hyperalgesia persisted for over 24 h. The
      NK(1) receptor antagonists, SDZ NKT 343, RPR100893 and SR140333, reduced
      mechanical hyperalgesia by 68, 36 and 27% at a dose of 30 mg kg(-1) p.o.,
      respectively. No further reduction was noted at higher doses (maximum 100 mg kg(
      1) p.o.). The anti-hyperalgesic effect of SDZ NKT 343 and RPR100893 peaked at 3 h
      while SR140333 produced maximal reversal at 1 h after oral administration. D(30)
      values indicated significant differences between the potency of these compounds.
      SDZ NKT 343 was by far the most potent anti-hyperalgesic agent (D(30): 1.1 mg kg(
      1)). The D(30) values for RPR100893 and SR140333 were estimated to be 17 and >100
      mg kg(-1), respectively. In thermal hyperalgesia, SDZ NKT 343 produced a
      significantly weaker anti-hyperalgesic effect with a peak of 25% reversal. The
      D(30) value for SDZ NKT 343 was 3.89 mg kg(-1). For comparison, morphine
      inhibited the carrageenan-induced mechanical and thermal hyperalgesia with an
      ED(50) of 1.85 and 2.51 mg kg(-1) s.c., respectively. When tested up to 300 mg
      kg(-1) p.o., aspirin reduced carrageenan-induced mechanical and thermal
      hyperalgesia by 55.0 and 45.2%, respectively. In addition to the anti
      hyperalgesic effects of NK(1) receptor antagonists, the effects of SDZ NKT 343
      and RPR100893 on plasma protein extravasation were measured in the FCA-treated
      knee joint of the guinea-pig. SDZ NKT 343 reversed plasma protein extravasation 2
      h after administration by 60% at the oral dose of 30 mg kg(-1). RPR100893 was
      significantly less effective with a maximum reversal of 30% at 100 mg kg(-1). In
      comparison, indomethacin produced a 50% reversal at a 10 mg kg(-1) dose. These
      experiments indicate that the carrageenan-induced hyperalgesia in the guinea-pig
      may be predictive of analgesic activity of NK(1) receptor antagonists in man.
      NK(1) receptor antagonists are active anti-hyperalgesic drugs in both mechanical
      and thermal hyperalgesia in the guinea-pig. In addition they inhibit plasma
      protein extravasation in the same species. The variability of in vivo potency and
      efficacy of the NK(1) receptor antagonists in the mechanical hyperalgesia model
      is difficult to interpret as all compounds are highly effective at blocking the
      NK(1) receptor in guinea-pig tissues. Amongst several possibilities, differences
      in pharmacokinetics may explain discrepancies.

PMID- 10963908
TI  - Prediction of return-to-work of low back pain patients sicklisted for 3-4 months.
AB  - The purpose of this Dutch prospective population-based study was to identify
      prognostic factors for return-to-work of employees with 3-4 months sick leave due
      to low back pain (LBP). A cohort of 328 employees was formed and baseline data
      were collected. One year after the first day of the sick leave, 91% of the
      original cohort participated in a second interview (n=298). During the baseline
      measurement, information was collected about health status, history of LBP,
      occupational variables, job characteristics and social economic variables. At the
      second interview, 66% of the employees had returned to work (n=198). Return-to
      work was independently predicted by having a better general health status (OR
      1.53; 95% CI 1.30-1.80), having better job satisfaction (OR 1.26; 95% CI 1.11-1.
      44), being a bread winner (OR 2.46; 95% CI 1.37-4.40), having a lower age (OR
      0.70; 95% CI 0.52-0.93) and reporting less pain (OR 0. 85; 95% CI 0.73-0.99) all
      measured at cohort entry. This study shows that psycho-social aspects of health
      and work in combination with economic aspects have a significantly larger impact
      on return-to-work when compared to relatively more physical aspects of disability
      and physical requirements of the job. This suggests that interventions aimed at
      return-to-work of employees sicklisted with LBP should predominantly be focused
      on these psycho-social aspects such as health behavior and job satisfaction, and
      on the (lack of) economic incentives for return-to-work.

PMID- 10963907
TI  - Psychophysical examination in patients with post-mastectomy pain.
AB  - Chronic pain, lymphoedema, post-irradiation neuropathy and other symptoms are
      reported in as many as 75% of women following breast cancer treatment. This study
      examined pain and sensory abnormalities in women following breast cancer surgery.
      Sensory tests were carried out on operated and contralateral sides in 15 women
      with spontaneous pain and sensory abnormalities and 11 pain-free women. Testing
      included the VAS score of spontaneous pain, detection and pain threshold to
      thermal and mechanical stimuli, temporal summation to repetitive heat and
      pinprick stimuli, and assessment of skin blood flow during repetitive brush and
      pinprick stimulation. Sensory threshold to pinprick and thermal stimuli was
      significantly higher on the operated side in both groups while pressure pain
      threshold was significantly lower in pain patients on the operated side compared
      to the contralateral side. No side to side difference was seen in pressure pain
      threshold in the pain-free group. Evoked pain intensity to repetitive stimuli at
      0.2 and 2.0 Hz was significantly higher on the operated side in pain patients
      compared to the control area while no such difference was seen in pain-free
      patients. Cutaneous blood flow measured by laser Doppler (flux) was significantly
      higher when the skin was tapped at 2.0 Hz on the operated side compared to
      contralaterally in pain patients, while no side to side difference was seen in
      pain-free patients. Pinprick-evoked pain was correlated to spontaneous pain but
      not to flux. Spontaneous pain was not correlated to flux. Sensitization seems to
      be a feature in breast cancer-operated women with pain, but not in pain-free
      women.

PMID- 10963909
TI  - Positron emission tomography study of a chronic pain patient successfully treated
      with somatosensory thalamic stimulation.
AB  - Previous neuroimaging studies suggested that the neuronal network underlying the
      perception of chronic pain may differ from that underlying acute pain. To further
      map the neural network associated with chronic pain, we used positron emission
      tomography (PET) to determine significant regional cerebral blood flow (rCBF)
      changes in a patient with chronic facial pain. The patient is implanted with a
      chronic stimulation electrode in the left ventroposterior medial thalamic nucleus
      with which he can completely suppress his chronic pain. The patient was scanned
      in the following conditions: before thalamic stimulation (pain, no stimulation),
      during thalamic stimulation (no pain, stimulation) and after successful thalamic
      stimulation (no pain, no stimulation). Comparing baseline scans during pain with
      scans taken after stimulation, when the patient had become pain-free, revealed
      significant rCBF increases in the prefrontal (Brodmann areas (BA) 9, 10, 11 and
      47) and anterior insular cortices, hypothalamus and periaqueductal gray
      associated with the presence of chronic pain. No significant rCBF changes
      occurred in thalamus, primary and secondary somatosensory cortex and anterior
      cingulate cortex, BA 24'. Significant rCBF decreases were observed in the
      substantia nigra/nucleus ruber and in the anterior pulvinar nucleus. During
      thalamic stimulation, blood flow significantly increased in the amygdala and
      anterior insular cortex. These data further support that there are important
      differences in the cerebral processing of acute and chronic pain.

PMID- 10963910
TI  - Understanding the adoption of arthritis self-management: stages of change
      profiles among arthritis patients.
AB  - Clinical observations and recent studies suggest that arthritis patients vary
      considerably in their involvement in self-management efforts. In the literature
      on health promotion, there is growing recognition that patients may be at
      different stages of change with respect to the adoption of self-management
      strategies. The major goal of the present study was to examine whether cluster
      analysis could be used to identify homogeneous subgroups of patients having
      persistent arthritis pain based on their responses to a stages of change
      questionnaire. Participants in this study (103 patients having rheumatoid
      arthritis and 74 patients having osteoarthritis) completed a stages-of-change
      measure specific to adoption of a self-management approach to their arthritis. A
      cluster analysis identified five distinct subgroups of arthritis patients: (1)
      precontemplation - 44% of the sample; (2) contemplation - 11% of the sample; (3)
      preparation - 22% of the sample; (4) unprepared action - 6% of the sample; and
      (5) prepared maintenance - 17% of the sample. These subgroups are generally
      consistent with what might be expected based on the transtheoretical model of
      stages of change by Prochaska and DiClemente (Prochaska JO, DiClemente CC.
      Towards a comprehensive, transtheoretical model of change: states of change and
      addictive behaviors. In: Miller WR, Heather N, editors. Applied clinical
      psychology, 2nd ed. Treating addictive behaviors, New York: Plenum Press, 1998.
      pp. 3-24.), and may have important clinical implications. For example, it is
      possible that the arthritis subgroups identified may predict arthritis patients'
      participation in and responsiveness to pain-coping skills training, exercise
      interventions, or other formal self-management training programs. Also, one may
      be able enhance the outcomes of self-management interventions for arthritis by
      tailoring treatment to the patient's particular stage.

PMID- 10963911
TI  - Functional magnetic resonance imaging in rats subjected to intense electrical and
      noxious chemical stimulation of the forepaw.
AB  - We examined whether cerebral activation to two different intense and painful
      stimuli could be detected using functional magnetic resonance imaging (fMRI) in
      alpha-chloralose anesthetized rats. Experiments were performed using a 9.4 T
      magnet and a surface coil centered over the forebrain. A set of gradient echo
      images were acquired and analyzed using our software based on fuzzy cluster
      analysis (EvIdent). Following the injection of 50 microl of formalin (5%) into
      the forepaw we observed a regional increase in signal intensity in the MR images
      in all animals. Anterior cingulate cortex, frontal cortex and sensory-motor
      cortex were some of the regions that activated frequently and often bilaterally.
      Surprisingly, activation appeared sequentially, often occurring first in either
      the right or the left hemisphere with a separation of seconds to minutes between
      peak activations. Morphine pre-treatment (1 mg/kg, i. v.) delayed and/or reduced
      the intensity of the activation resulting in a decrease in the overall response.
      Following episodes of intense electrical stimulation, produced by two brief
      stimulations (15 V, 0. 3 ms, 3 Hz) of the forepaw, activation was observed
      consistently in the sensory-motor cortex contralateral to the stimulation.
      Activation also occurred frequently in the anterior cingulate cortex, ipsilateral
      sensory-motor cortex and frontal cortical regions. All these regions of
      activation were markedly reduced during nitrous oxide inhalation. Treatment with
      morphine resulted in an inhibition of the activation response to electrical
      stimulation in most regions except for sensory-motor cortex. Thus, electrical and
      chemical noxious stimuli activated regions that are known to be involved in the
      central processing of pain and morphine modified the activation observed. fMRI
      combined with appropriate exploratory data analysis tools could provide an
      effective new tool with which to study novel analgesics and their effects on the
      CNS processing of pain in animal models.

PMID- 10963912
TI  - The relationship of gender to pain, pain behavior, and disability in
      osteoarthritis patients: the role of catastrophizing.
AB  - One hundred and sixty-eight patients with osteoarthritis (OA) of the knees
      participated in this study. Of the participants, 72 were men and 96 were women.
      All participants completed the Arthritis Impact Measurement Scales (AIMS),
      underwent a 10 min standardized observation session to assess their pain
      behavior, and completed the Catastrophizing Scale of the Coping Strategies
      Questionnaire (CSQ) and the Depression Scale of the Symptom Checklist 90 Revised
      (SCL-90R). The study found that there were significant differences in pain, pain
      behavior, and physical disability in men and women having OA. Women had
      significantly higher levels of pain and physical disability, and exhibited more
      pain behavior during an observation session than men. Further analyses revealed
      that catastrophizing mediated the relationship between gender and pain-related
      outcomes. Once catastrophizing was entered into the analyses, the previously
      significant effects of gender were no longer found. Interestingly,
      catastrophizing still mediated the gender-pain relationship even after
      controlling for depression. These findings underscore the importance of both
      gender and catastrophizing in understanding the OA pain experience and may have
      important implications for pain assessment and treatment.

PMID- 10963914
TI  - Imaging of degenerative and posttraumatic disease in the shoulder joint

PMID- 10963913
TI  - Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its
      relation to changes in dorsal root ganglion blood flow.
AB  - Transection of the L5 spinal nerve in rats results in allodynia- and hyperalgesia
      like behavior to mechanical stimulation which are thought to be mediated by
      ectopic activity arising in lesioned afferent neurons mainly in the dorsal root
      ganglion (DRG). It has been suggested that the neuropathic pain behavior is
      dependent on the sympathetic nervous system. In rats 3-56 days after L5 spinal
      nerve lesion, we tested responses of axotomized afferent fibers recorded in the
      dorsal root of the lesioned segment to norepinephrine (NE, 0.5 microg/kg)
      injected intravenously and to selective electrical stimulation of the lumbar
      sympathetic trunk (LST). In some experiments we measured blood flow in the DRG by
      laser Doppler flowmetry. The majority of lesioned afferent fibers with
      spontaneous activity responded to neither LST stimulation (82.4%) nor NE (71.4%).
      In those which did react to LST stimulation, responses occurred only at high
      stimulation frequencies (likely to be above the physiological range), and they
      could be mimicked by non-adrenergic vasoconstrictor drugs (angiotensin II,
      vasopressin). Excitatory responses to LST stimulation were closely correlated
      with the stimulation-induced phasic vasoconstrictions in the DRG. We therefore
      hypothesized that the activation of lesioned afferents might be brought about
      indirectly by an impaired blood supply to the DRG. To test this hypothesis we
      induced a strong and sustained baseline vasoconstriction in the DRG by blocking
      endothelial nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L
      NAME) applied systemically. L-NAME enhanced baseline vascular resistance in the
      DRG about threefold and also increased stimulation-induced vasoconstrictions.
      After L-NAME, the majority of axotomized neurons with spontaneous activity were
      activated by LST stimulation (76%) or NE (75%). Again, activations closely
      followed stimulation-induced phasic vasoconstrictions in the DRG provided that a
      critical level of vasoconstriction was exceeded. In the present study, inhibitory
      responses to LST stimulation were generally rare and could be reversed to
      activation by prolonged stimulation or after L-NAME. These results show that
      sympathetic-sensory coupling occurs only in a minority of axotomized afferents
      after L5 spinal nerve injury. Like previous studies, they cast doubt on the
      notion that the L5 spinal nerve lesion is a good model for sympathetically
      maintained pain. Since responses of lesioned afferent neurons to LST stimulation
      and NE could be provoked with high reliability after inducing vasoconstriction in
      the DRG, and since they mirrored stimulation-induced vasoconstrictions in the
      DRG, it appears that in this model the association of sympathetic activity with
      afferent discharge occurs mainly when perfusion of the DRG is impaired.

PMID- 10963915
TI  - Anatomical basics, variations, and degenerative changes of the shoulder joint and
      shoulder girdle.
AB  - This paper summarizes the anatomical basics of the shoulder, their variations,
      and precise definitions, including differential diagnoses. It also describes the
      characteristic degenerative changes caused by aging. A typical variation (7-15%)
      is the os acromiale, which forms the triangular epiphysis of the scapular spine.
      This abnormality must be differentiated from a fracture of the acromion or a
      pseudarthrosis. Because ossification of the acromion is complete after age 25,
      the os acromiale should be diagnosed only after this age. The shape of the
      acromion is a further important feature. In a recent anatomical study, the
      following frequencies of the Bigliani-types of the acromial shape were
      anatomically determined - type 1 (flat), 10.2% and type 2 (curved), 89.8%. Type 3
      (hooked) was not observed, which indicates that this type is probably a
      misinterpretation of the so-called acromial spur. Minor dehiscences and
      perforations in the infraspinate or supraspinate fossa should not be confused
      with malignant osteolyses. The scapula has three ligaments of its own, (1) the
      coracoacromial ligament and its osseous fixations form an osteofibrous arch above
      the shoulder joint, which plays a part in impingement syndrome; (2) the superior
      transverse scapular ligament or its ossified correlate arches the scapular
      incisure and can cause a typical compression syndrome of the suprascapular nerve;
      (3) the inferior transverse scapular ligament is of no great clinical importance.
      Two intraarticular structures (glenoid labrum and tendon of the long bicipital
      head) must be mentioned. The glenoid labrum consists of dense connective tissue
      and surrounds the margin of the glenoid cavity. Two areas exhibit specialized
      conditions, cranial at the supraglenoid tubercle an intimate relationship exists
      to the tendon of the long bicipital head and in about 55% of cases, the labrum is
      stretched over the glenoid rim at the ventral side. At the area of the biceps
      tendon-labrum complex, so-called SLAP-lesions may occur and at the glenoid rim,
      where the labrum is often not fixed to the bony margin, avulsions of the labrum
      may occur. This well-established anatomical condition must not be mistaken for a
      manifest Bankart-lesion. The glenohumeral ligaments, which are located in the
      ventral articular capsule, have a stabilizing function for the ventral part of
      the glenoid labrum. The glenohumeral ligaments lift the articular lip where it
      crosses the glenoid notch. This 'labrum-lift effect' supports the stabilizing
      features of the articular lip and the glenohumeral ligaments. The rotator cuff is
      composed of the tendons of the teres minor, infraspinatus, supraspinatus, and
      subscapularis muscles. This cuff has a poorly vascularized area, due to
      mechanical conditions, about 1.5 cm from the major tubercle, which causes
      degenerative changes and eventually may lead to ruptures. Results of the
      impingement-syndrome and the osteoarthrotic changes of the shoulder and
      acromioclavicular joint are also presented and discussed. Finally, the
      coracoclavicular joint, which probably represents no congenital entity but
      appears due to a changed, lowered position of the shoulder girdle, is discussed.
      The paper also presents instructive figures of anatomical preparations that can
      be used to make more precise radiological and differential diagnoses. All
      preparations were done by the author and are part of a series of more than 300
      preparations of the shoulder joint and girdle.

PMID- 10963916
TI  - Classification, clinical findings and operative treatment of degenerative and
      posttraumatic shoulder disease: what do we really need to know from an imaging
      report to establish a treatment strategy?
AB  - Successful patient care involves interdisciplinary Cupertino. Images allow an
      interpretation of a static dimension, but may not be sufficient to develop a
      surgical treatment strategy, since many shoulder problems have its origin in a
      dynamic pathology. This article outlines dynamic clinical tests of shoulder
      pathology, classifies various degenerative and posttraumatic shoulder problems
      and stresses key facts an imaging report should include in order to plan surgery.
      This article conveys basic knowledge of those tests and the dynamic background of
      shoulder pathology. Basic surgical treatment principles are summarised briefly.

PMID- 10963917
TI  - Imaging of degenerative and posttraumatic disease in the shoulder joint with
      ultrasound.
AB  - This article reviews the examination technique of shoulder ultrasound, normal and
      abnormal ultrasound findings in acute (posttraumatic) and chronic (degenerative)
      lesions. Moreover, it reviews the effectiveness of ultrasound in relation to
      magnetic resonance (MR) imaging. Most authors report that full-thickness tears of
      the supraspinatus can reliably be diagnosed by ultrasound. However, the simple
      diagnosis of a full-thickness rotator cuff tear is no longer sufficient for
      surgical management. The precise localization and size of rotator cuff tears as
      well as the extent of muscle degeneration is important for surgical planning. For
      this aspect and for partial-thickness tears of the supraspinatus, for
      subscapularis lesions as well as for lesions of the long biceps tendons there is
      no consensus regarding the diagnostic value of ultrasound. To the present,
      ultrasound (contrary to MR imaging) has failed to demonstrate that it
      consistently influences the clinician's degree of confidence in the clinical
      diagnosis or the treatment plan. Therefore, some orthopedic surgeons prefer MR
      imaging to ultrasound in the evaluation of rotator cuff tears and other
      abnormalities of the glenohumeral joint. Moreover, MR imaging, especially when
      combined with arthrography, represents a one-step investigation, which not only
      allows for assessment of rotator cuff lesion but also of lesions of the labrum
      (Bankart lesions, SLAP lesions), the joint capsule and the biceps tendon. It also
      demonstrates muscle atrophy, which represents an important predictor of surgical
      outcome in rotator cuff repair.

PMID- 10963918
TI  - MR and MR arthrography to identify degenerative and posttraumatic diseases in the
      shoulder joint.
AB  - MR imaging provides a comprehensive evaluation of a wide spectrum of both
      intraarticular and extraarticular pathology of the shoulder. MR imaging enables
      the detection or exclusion of degenerative and posttraumatic diseases of the
      shoulder with a reasonable accuracy. MR arthrography is useful in the
      visualization of subtle anatomic details and further improves the
      differentiation. In this article, findings of MR imaging and MR arthrography of
      degenerative and posttraumatic shoulder diseases (impingement syndrome, rotator
      cuff tears, and glenohumeral instability) has been reviewed.

PMID- 10963919
TI  - Radiographic appearance of the chest following therapy for Hodgkin disease.
AB  - This study was carried out to define the post-treatment appearance of the chest
      radiographs in 44 consecutive patients with Hodgkin disease who received mantle
      irradiation with or without chemotherapy and to determine how the incidence and
      severity of post-treatment abnormalities relate to the radiation parameters and
      chemotherapeutic regimens. Radiographs of the chest in 44 patients, computed
      tomograms of the chest in 31 patients and of the abdomen of 35 patients were
      reviewed, prior to and following treatment, for mediastinal contours, pericardial
      status, cardiac size and pulmonary fibrosis. All patients were followed for a
      minimum of 1 year and 27 were followed for more than 5 years. Stable post
      treatment imaging studies were correlated with the initial extent of disease,
      radiation parameters, and chemotherapeutic regimens. Stable post-treatment
      findings were categorised as follows: the chest radiograph was normal or showed
      subtle vascular reorientation; moderate paramediastinal fibrosis was present;
      severe pulmonary fibrosis had occurred with narrowing of the cardiomediastinal
      silhouette in some patients. In general, the severity of the fibrosis was
      dependent on (1) the size of the radiation fields and on whether or not the
      coverage of the hila included a 1- to 2-cm margin; (2) the amounts of
      chemotherapy and particularly bleomycin containing regimens and (3) individual
      susceptibility of normal tissue irradiation. Therapy for Hodgkin disease is not
      necessarily associated with radiographic sequelae regardless of the initial
      status of the mediastinum or the treatment. However, the post-treatment
      appearance of the chest radiographs in this study was related strongly to (1) the
      initial extent of disease and particularly the status of the hila, both of which
      influenced the amounts of lung parenchyma that were included in the treatment
      fields; (2) the use of bleomycin in chemotherapy regimens and (3) individual
      normal tissue radiosensitivity.

PMID- 10963920
TI  - Quiz case. Primary B-cell lymphoma of the nasolacrimal duct.

PMID- 10963921
TI  - Addiction severity index data from general membership and treatment samples of
      HMO members. One case of norming the ASI.
AB  - The Addiction Severity Index (ASI) is a widely used interview among substance
      dependent populations in treatment. Its value as a treatment planning and
      evaluation tool has been diminished by the lack of comparative data from
      nonclinical samples. The present study included four scales from the ASI
      collected on samples of adult subscribers to a large health maintenance
      organization (HMO) in northern California, as well as an adult clinical sample
      from the same geographic region with the same HMO insurance, thereby offering
      informative contrasts. Interviews (N = 9,398) of non-alcohol-dependent or abuse
      adults from a random sample of members of a large HMO were analyzed. We collected
      complete ASI data on the alcohol, drug, medical, and psychiatric composite scales
      and partial data on the employment scale. A sample of 327 adult members of the
      same HMO from one of the counties included in the survey, who were admitted to
      treatment for alcohol and/or drug addiction, was administered the same ASI items
      at treatment admission. Analyses compare problem severities in the two samples by
      age and gender. The general membership reported some problems in most of the ASI
      problem areas, although at levels of severity that were typically far below those
      seen in the clinical sample. General membership and clinical samples were
      somewhat similar in medical status and in employment. As expected, alcohol, drug,
      and psychiatric status were much more severe in the clinical sample. The data
      from the HMO general membership sample provide one potential comparison group
      against which to judge the severity of problems presented by drug- and alcohol
      dependent patients at treatment admission and at posttreatment follow-up. The
      authors discuss the implications for treatment planning and the evaluation of
      treatment outcome.

PMID- 10963922
TI  - Report of an integrated brief intervention with self-defined problem cannabis
      users.
AB  - A range of strategies have been employed elsewhere to treat cannabis dependency,
      but until recently few treatment options were available in Australia. This
      article discusses the development and evaluation of the trial on a Integrated
      Brief Intervention (IBI) with self-defined problem cannabis users in Melbourne.
      Sixty-one people were recruited to the intervention between December 1997 and
      June 1998. Participants received a brief one-to-one clinical assessment interview
      and received self-help materials. Due to time limitations only 33 persons were
      eligible for inclusion in the evaluation involving follow-up interviews at 1 and
      3 months to assess the impact of the intervention. Most participants reported a
      marked reduction in the frequency and/or quantity of cannabis used. These
      positive changes in patterns of use are reported to have resulted in improved
      health and social functioning. It is suggested that while these results support
      the use of brief interventions, further research is needed to determine whether
      this type of brief intervention is a cost-effective way for treating cannabis
      dependency.

PMID- 10963923
TI  - Burnout in substance abuse counselors. Impact of environment, attitudes, and
      clients with HIV.
AB  - Due to associations between acquired immunodeficiency sydnrome (AIDS) and
      substance abuse, many substance abuse treatment counselors have clients with
      human immunodeficiency virus (HIV)/AIDS. We assess the contribution of various
      hypothesized predictors of burnout among 134 substance abuse counselors working
      with clients with HIV/AIDS. Counselors reported practice-related variables,
      including support from coworkers and supervisors, caseload, percentage of HIV
      positive clients, and whether they worked at a methadone clinic, and personal
      characteristics of job efficacy and education. The three burnout dimensions were
      emotional exhaustion, depersonalization, and personal accomplishment. Emotional
      exhaustion was significantly predicted by less support, less efficacy, and
      working in a methadone clinic. Depersonalization was predicted by less efficacy,
      less support, and working in a methadone clinic. Personal accomplishment was
      predicted by having a lower percentage of clients with HIV/AIDS, and more
      efficacy, support, and education. We present empirically based suggestions for
      interventions that can prevent or limit burnout.

PMID- 10963924
TI  - Comparison of outcomes by gender and for fee-for-service versus managed care: a
      study of nine community programs.
AB  - During-treatment services and 7-month posttreatment entry outcome of cocaine- or
      alcohol-dependent men (n = 145) and women (n = 149) Target City patients
      receiving either standard fee-for-services (n = 183) or managed care treatment
      funding (n = 111) in nine community outpatient programs were compared. No
      differences were found in treatment services received by the various subgroups.
      Regression analyses compared the four described subgroups (Gender x Type of
      Funding) on their seven Addiction Severity Index composite scores at 7 months
      postadmission controlling for the respective baseline composite score and several
      background variables on which the groups differed. Surprisingly few outcome
      differences were revealed between men and women patients and patients receiving
      the two forms of treatment funding. The only difference noted was that patients
      treated via managed care showed more improvement in the drug area. The need for
      further evaluation of the effects of managed care is emphasized.

PMID- 10963925
TI  - A study of barriers to the engagement of significant others in adult addiction
      treatment.
AB  - Using the focus group methodology, this study identified personal and structural
      barriers to the engagement of significant others in an outpatient addictions
      treatment program. Twenty-eight significant others (family members, other kin,
      and friends) associated with 21 patients participated in one of three focus group
      sessions. The cut-and-paste technique was used to analyze the narrative data.
      Improving communication and reconnecting patients with a supportive community
      were forms of support identified. Patients' willingness to accept support and
      therapists' invitation to involve significant others in the treatment were
      identified as necessary precursors to their initial involvement. Providing
      educational and therapeutic support to significant others were endorsed as
      important elements in maintaining their involvement. Offering a diversity of
      therapeutic services beyond standard office hours, providing home visits and
      child care were viewed as facilitators for their involvement. It became apparent
      that support providers tended to resent having their own needs ignored. Feelings
      of isolation, fatalism, loneliness, ignorance, and fear were expressed by
      significant others. Theoretical and practical implications of the findings are
      discussed.

PMID- 10963926
TI  - Predicting retention in a residential drug treatment alternative to prison
      program.
AB  - One hundred and fifty felony drug offenders diverted from prison to community
      based, residential drug treatment alternative to prison program completed a
      comprehensive interview as part of a longitudinal study. Treatment completion
      predictors were sought examining intake data (demographics, family, social,
      employment, medical, psychological, criminal, sexual behavior, drug use and
      treatment histories). Logistic regression results found completers had more
      social conformity and close friends, and less need for employment counseling,
      felony drug convictions, drug dealing income, and unprotected sex than dropouts.
      Completers were also less likely to encounter recent problems with significant
      other, have a psychiatric history, experience gunshot or stabbing, and commenced
      heroin use at older ages than dropouts. However, completers reported higher
      alcohol use than counterparts. Further analyses explored subcategory models:
      "life choice" (substance use, criminal and sexual behavior), static (background
      and dispositional), and dynamic situational influences (employment, psychological
      state, recent and past encounters). Treatment implications considering findings
      are discussed.

PMID- 10963927
TI  - A comparison of substance abuse patients' and counselors' perceptions of relapse
      risk: relationship to actual relapse.
AB  - This study compared substance abuse patients' and their counselors' perceptions
      of relapse risk during treatment and evaluated whether these perceptions predict
      actual relapse 2 years later. Participants (N = 240) completed the Relapse Risk
      Index (RRI), which assesses confidence in abilities and need for services across
      four domains: coping skills, social support, resources, and leisure activities.
      Participants reported greater confidence and greater needs than counselors
      reported. Determinants of counselors' relapse risk perceptions included income,
      whereas participants' perceptions were related to polysubstance use. Counselors'
      ratings of coping skills predicted alcohol relapse; counselors' ratings did not
      predict drug relapse. Participants' ratings of coping skills and leisure
      activities predicted alcohol relapse; social support predicted drug relapse. When
      including background characteristics, counselors' ratings did not predict alcohol
      or drug relapse; participants' ratings predicted alcohol relapse but not drug
      relapse. Findings suggest the potential utility of considering patient
      perceptions to understand and possibly prevent relapse.

PMID- 10963928
TI  - Addiction problems and methadone treatment.
AB  - This article reports on a study of the addiction problems of 397 heroin-addicted
      clients who applied to join a methadone program at an addiction center in The
      Hague (The Netherlands). Each client was assessed during the intake phase
      according to the Revised Addiction Severity Index (ASI-R). The results show that
      for a large group of the methadone clients (minimum of one third) there is an
      indication for treatment in the life areas of Employment, Drug Use, Legal Status,
      Social Functioning, and Psychological Functioning of the ASI-R. The article
      concludes with some recommendations.

PMID- 10963929
TI  - Substance abuse and childhood maltreatment. Conceptualizing the recovery process.
AB  - Research exploring the dual, yet related, issues of adulthood substance abuse and
      childhood maltreatment remains limited to the effects of such experiences on the
      individual. To date, clinical literature has failed to explore the ways in which
      individuals, particularly women, cope with and recover from these experiences.
      The current study applied a qualitative methodology to a sample of six women.
      Respondents had completed a minimum of 3 years of chemical-free living and self
      identified as survivors of prolonged childhood sexual abuse. Women participated
      in a semi-structured interview to detail their recovery process. Results show
      support for a multifactorial process of recovery; specifically, strategies aimed
      at affect regulation, development of a new self-concept, and the forging of more
      adaptive attachment styles. The implications of these results are discussed in
      the context of improving clinical intervention strategies and encouraging
      additional research endeavors to understand this complex process.

PMID- 10963931
TI  - Treating substance abuse in the context of severe and persistent mental illness:
      clinicians' perspectives.
AB  - Patients with comorbid substance use and major mental disorders are treated
      frequently in the mental health system. Treatment models relevant for this subset
      of patients have emerged in recent years, however, few have been validated
      empirically and so relatively few sites benefit from this treatment development
      activity. Important additional sources of information about good treatment
      practices are the clinicians who have adopted the treatment of patients with dual
      disorders as a specialty. We conducted four focus groups (N = 12) with clinicians
      who were nominated by their peers as experienced and/or expert in treating
      persons with comorbid substance use and psychiatric disorders. Discussions
      followed a four-part outline that included (a) general questions about training
      and experience with the population, (b) preferred treatment methods, (c)
      motivational issues, and (d) recommendations to the field. Participants were
      trained in a variety of mental health disciplines and pursued substance abuse
      treatment credentials or other educational experiences outside of their primary
      training programs. Their treatment approaches emphasized psychoeducation, a good
      therapeutic relationship, and the need to be flexible regarding methods and
      goals. Abstinence was the preferred goal among most clinicians; even so, they
      expressed a pragmatic flexibility and other views consistent with the principles
      of harm reduction. Clinicians tended to respond to patients' ambivalent
      motivational states by addressing the consequences of behaviors in a
      nonconfrontive style; they also made use of positive incentives and external
      support. A number of recommendations were made to improve treatment, including
      greater institutional and programmatic support for the unique needs of this
      population.

PMID- 10963930
TI  - Matching alcoholics to treatment. Failure to replicate finding of an earlier
      study.
AB  - The purpose of the present study was to investigate whether sociopathic
      alcoholics respond differentially to different types of treatment. An earlier
      study found that alcoholics with antisocial personality disorder had somewhat
      better outcomes if treated in individually focused versus relationship-focused
      cognitive-behavioral treatment. The present study was designed to attempt to
      replicate these findings. One hundred and forty-nine alcoholics (42 of whom
      scored high on a measure of sociopathy) were randomly assigned to receive either
      individually focused cognitive-behavioral treatment or a relationship-focused
      community reinforcement approach. Follow-up evaluations were conducted every 4
      months for 2 years. Results failed to support the study hypothesis. Drinking
      outcomes were similar for sociopathic alcoholics in both treatment conditions.
      Directions for future research are identified.

PMID- 10963932
TI  - Acupuncture for addicted patients with chronic histories of arrest. A pilot study
      of the Consortium Treatment Center.
AB  - Auricular acupuncture continues to gain popularity as an adjunct to substance
      abuse treatment. This report describes an outcomes study in a treatment center
      tailored to the needs of chronic repeat offenders. Thirty-seven patients who
      received acupuncture (AC) during the early weeks of treatment were followed for
      180 days postadmission. Data were collected for four parameters: (1) program
      retention, (2) new arrests incurred, (3) drug-positive urinalysis results, and
      (4) number of days needed to progress from entry level to secondary level
      treatment. These data were compared to archived information from 49 no
      acupuncture (NA) patients who had entered the program before acupuncture became
      available. Chi-square tests determined that AC patients exhibited significantly
      higher program retention than NA patients at 30 (p < 0.0001), 60 (p <.002), 90 (p
      <. 001), 120 (p <.007), and 150 (p <.031) days. At 180 days, a higher percentage
      of AC patients than NA patients remained in treatment, but the difference was not
      significant. Kaplan-Meier survival analysis determined that AC patients had
      significantly higher cumulative probability of remaining in treatment than did NA
      patients (p <.0021). In AC patients, there were decreased numbers of new arrests,
      drug-positive urinalysis results, and days needed to advance in treatment, but
      the differences were not significant. Fifty-one percent of all patients named
      methamphetamine as their primary drug of choice. Regardless of treatment group,
      methamphetamine-addicted patients exhibited significantly lower program retention
      than patients addicted to all other drugs (p <. 035). In methamphetamine-addicted
      patients, acupuncture improved program retention only up to 30 days (p <.021).
      These findings support addition of acupuncture to substance abuse treatment for
      criminal justice clients and indicate a need for acupuncture research focusing on
      withdrawal from methamphetamine.

PMID- 10963933
TI  - Neonatal nicotine administration influences ethanol-induced behaviors.
AB  - Neonatal mice were administered nicotine (66 microg (-)-nicotine base/kg body
      weight (bw) s.c. twice daily at 0800 and 1700 h on postnatal days 10 and 14) and
      control mice received saline (10 ml 0. 9% NaCl/kg bw s.c.) on the same occasions.
      Behavioral testing was initiated 3 months after birth. In Experiment 1, neonatal
      nicotine administration did not affect spontaneous motor activity but altered the
      peak dose stimulatory effect of ethanol upon locomotion and rearing activity from
      3.0 mg/kg, in the control mice, to 1.5 mg/kg. Administration of the nicotine
      antagonist, mecamylamine (MEC, 2.0 mg/kg), had no effect upon the peak dose
      stimulatory effect (i.e., 1. 5 mg/kg) evidenced in the nicotine-treated mice, but
      attenuated the stimulatory effect of the 3.0 mg/kg dose of ethanol in the control
      mice. In Experiment 2, the effects of neonatal nicotine administration upon
      ethanol intake and preference were assessed. In the single fluid access (one
      bottle) test, nicotine-treated mice consumed both more ethanol (2%, 4%, or 6%
      concentrations) and more tap water than control mice. In the two-bottle ethanol
      preference test, nicotine-treated mice consumed more ethanol and tap water.
      Further analysis of the high-preferring (HP) ethanol mice indicated higher
      ethanol intake and preference in the nicotine-treated mice but no differences in
      tap water or total fluid intake. The present findings are considered together
      with prevailing notions of nicotine receptor alterations and possible cross
      sensitization effects modulating substance abuse.

PMID- 10963934
TI  - Effects of chronic ethanol exposure on acetaldehyde and free radical production
      by astrocytes in culture.
AB  - In a previous study, the production of acetaldehyde and free radicals derived
      from ethanol was characterized in astrocytes in primary culture. In the present
      study, the effects of chronic exposure on the production of both compounds as
      well as on the main antioxidant system were compared with those of an acute
      exposure. This was done to better understand the different ways the brain reacts
      to these modes of exposure. Under these conditions, both a time-dependent
      increase in the accumulation of acetaldehyde and a decreased formation of the
      alpha-hydroxyethyl radical were shown. This was associated with increased
      activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase
      (GPX) and with decreased glutathione (GSH) content. These effects, which
      counteract reactive oxygen species (ROS) formation by stimulating the main
      enzymes of the antioxidant system, were also associated with the reduced amount
      of radicals derived from ethanol. This could be a beneficial effect, but this was
      counter-balanced by the increased rate of acetaldehyde accumulation, whose high
      toxicity is well known. All these effects underline the crucial role played by
      catalase which, on one hand converts hydrogen peroxide to water and, on the other
      hand, ethanol to acetaldehyde.

PMID- 10963935
TI  - Chronic alcohol exposure and lactation: extended observations.
AB  - Previous results from our laboratory have indicated that chronic (8 days) alcohol
      administration inhibits suckling-induced prolactin (PRL) release in response to
      30 min of suckling. In addition, chronic alcohol administration to dams resulted
      in growth retardation of their litters. The present study was done to examine how
      an extended period of suckling (120 min) affected suckling-induced PRL release
      after chronic alcohol exposure. In addition, it was also examined whether the
      growth retardation observed during alcohol exposure persisted after alcohol
      infusions were discontinued. Dams were implanted with an atrial catheter on day 3
      of lactation and saline or alcohol (1.0- or 2.0-g/kg BW) was administered daily
      for 8 days (lactation days 5 through 12). Following administration of the initial
      alcohol dose, the infusion was continued at rates required to maintain blood
      alcohol levels (BALs) for 4 h each day. Testing took place on day 12. As
      previously reported, suckling-induced PRL release was inhibited in dams receiving
      2.0-g/kg alcohol after 30 min of suckling. However, after 120 min of suckling,
      PRL release in these dams was much higher than in either control or 1.0-g/kg
      alcohol dams. In addition, while the body weights of litters of dams administered
      2.0-g/kg alcohol were reduced compared to litters of dams in the other two groups
      on days 8-16, their body weights rebounded and were not different from the other
      litters on days 18 or 20.

PMID- 10963936
TI  - Alcohol before puberty produces an advance in the onset of sexual behavior in
      male rats.
AB  - The effect of alcohol consumption before puberty on the development of genital
      grooming (GG) and on the onset of sexual behavior was assessed. Wistar male rats
      were continuously exposed in a one-bottle access situation to either 6% ethanol
      (alcohol group, AG), an isocaloric sweetened solution (vehicle group, VG) or were
      maintained in standard laboratory conditions (control group, CG). Each solution
      was the only available liquid in each group from weaning (22 days) to 40 days of
      age. GG behavior was recorded from 25 to 47 days of age and sexual behavior was
      recorded from 42 to 74 days of age. The age at the maximum peak of both frequency
      and duration of GG showed an advance in the AG (33-35 days of age) compared with
      the CG (45 days) and the VG (47 days). An advance in the onset of sexual behavior
      was observed in the AG: at 46 days of age, seven of the nine males of this group
      showed ejaculatory behavior. In contrast, in the CG and VG, ejaculation occurred
      in at least 50% of subjects after 58 days of age. Regardless of the advance in
      the onset of sexual behavior, the characteristics of the different parameters of
      the copulatory sequence were not impaired by alcohol. The apparent advance in the
      onset of puberty is discussed in terms of the opioid hypothalamic activity as a
      mechanism that affects the LH secretion.

PMID- 10963937
TI  - The EPR study of LDL perturbed by alcohols with different molecular architecture.
AB  - In this work, the interaction of different isomers of lower aliphatic alcohols
      with LDL representing a complex macromolecular assembly is investigated in vitro.
      Emphasis is given to the comparison of the impact of molecular architecture of
      methanol, ethanol, propanol (n-, iso-) and butanol (n-, iso-, sec-, tert-) in
      perturbing the lipid-protein assembly. The geometrical characteristics as well as
      the lipophilicity of the respective alcohol are considered. The EPR method
      combined with the spin labeling of both the apoB and the lipid monolayer allowed
      parallel detection of changes provoked in both phases. In addition to the change
      in protein environment, the spectral decomposition of the experimental data
      revealed a decrease in lipid ordering with the increasing concentration of the
      alcohols. This phenomenon for aliphatic alcohols is linearly correlated with the
      equal volume occupation (EVO) of alcohol in LDL. The results support the
      molecular mechanism of alcohol action through its interference with the lipid
      protein interactions in LDL, which could be applicable to the molecular mechanism
      of alcohol interaction with integral membrane proteins.

PMID- 10963938
TI  - Diminished cardiac contractile response to tetrahydropapaveroline in
      hypertension: role of beta-adrenoceptors and intracellular Ca(2+).
AB  - Tetrahydropapaveroline (THP), a condensation product of ethanol-derived
      acetaldehyde, potentiates cardiac function through a beta-adrenergic mechanism.
      It is well established that beta-adrenergic activity is markedly depressed in
      hypertension. However, little is known about the myocardial action of THP in
      hypertension. In this study, the effect of THP was examined using left
      ventricular papillary muscles and ventricular myocytes from 10-week-old
      normotensive (WKY) and spontaneously hypertensive (SHR) rats. The mechanical
      parameters evaluated include: peak tension developed (PTD), peak twitch amplitude
      (PTA), time-to-PTD/PTA (TPT/TPS), time-to-90% relaxation/relengthening
      (RT(90)/TR(90)), and the maximal velocities of contraction/shortening and
      relaxation/relengthening (+/-VT/+/-dL/dt). Intracellular Ca(2+) transients were
      measured as fura-2 fluorescence intensity changes (delta FFI). THP (0.01-100
      microM) produced a concentration-dependent increase in myocardial contraction on
      muscles and myocytes from both groups of animals. However, preparations from the
      SHR group were generally less responsive to THP than their normotensive
      counterparts. The increase in contractility by THP was associated with increases
      in delta FFI and +/-VT, and shortening of TPT/TPS and RT(90)/TR(90). The role of
      beta-adrenoceptor(s) in the mechanism of action of THP was explored using
      specific beta-receptor subtype antagonists CGP 207.12A (beta(1)) and ICI 118,551
      (beta(2)). In preparations from both WKY and SHR hearts, the THP-induced increase
      in cardiac contractility was either attenuated or blocked by CGP 207. 12A and ICI
      118,551. These results indicate that THP exhibits a positive action on myocardial
      contraction that is mediated, in part, through both beta(1) and beta(2)
      adrenergic receptors. This cardiac inotropic response, however, is markedly
      diminished in hypertension, which is due possibly to alterations in beta
      adrenergic signal transduction.

PMID- 10963939
TI  - Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol
      withdrawal.
AB  - This study investigated the effects of a benzodiazepine partial agonist,
      abecarnil, and a full agonist, alprazolam, on ethanol withdrawal-induced anxiety
      like behaviors in rats. Anxiety was assessed in two models: elevated plus maze
      and pentylenetetrazol (GABA(A) antagonist) discrimination assay. Male rats
      received an ethanol-containing (4.5%) liquid diet for 7 to 10 days and were
      tested for withdrawal symptoms 12 h after termination of the diet. In the
      elevated plus maze, ethanol-withdrawn rats displayed less open arm activity and
      total arm entries than pair-fed rats. Abecarnil (0.08-0.32 mg/kg, IP) and
      alprazolam (0.08-1.25 mg/kg, IP) each produced a dose-dependent, full reversal of
      ethanol withdrawal-induced reduction of open arm activity, but only alprazolam
      increased the total arm entries. In the pentylenetetrazol assay, ethanol
      withdrawn rats selected the pentylenetetrazol lever (100%) over the salin-lever.
      Abecarnil (0.04-0.32 mg/kg, IP) and alprazolam (0.08-0.32 mg/kg, IP) dose
      dependently reduced pentylenetetrazol-lever responding to control levels (10
      20%). Alprazolam was more potent than abecarnil in reversing ethanol withdrawal
      induced decrease in open arm activities, but showed comparable potency and
      efficacy to abecarnil in blocking the pentylenetetrazol-like ethanol withdrawal
      stimulus. These results suggest that abecarnil and alprazolam may have
      therapeutic potential for treatment of ethanol withdrawal-induced anxiety-like
      symptoms.

PMID- 10963940
TI  - Effect of ethanol on thromboxane and prostacyclin production in the human
      placenta.
AB  - Fetal alcohol syndrome (FAS) is frequently associated with intrauterine growth
      retardation (IUGR). One cause of ethanol-induced IUGR is thought to be related to
      increased pressor activity in the human placenta, resulting in decreased
      oxygenation and nutrient transport to the fetus. Thus, we have investigated the
      effect of ethanol on paracrine substances, such as thromboxane and prostacyclin,
      that act as vasoregulators within the intrauterine tissues. In these studies we
      have utilized the perfused single human cotyledon system to study the effect of
      ethanol on placental prostanoid production. We assessed the effect of longer (240
      min) and more acute (60 min) exposure to ethanol on release of thromboxane B(2)
      (TxB(2)) and 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) at the
      maternal and fetal sides of the placenta. Thromboxane was increased by both
      longer and shorter ethanol exposure, especially on the fetal side of the
      placenta. Prostacyclin was essentially unchanged with exposure to ethanol. The
      thromboxane:prostacyclin ratio also tended to increase with both 60- and 240-min
      ethanol exposure, but a statistically significant increase was seen only at a few
      time points. In the 60-min ethanol exposure, an increase in thromboxane was
      observed both during and following exposure to ethanol. The increase in the
      thromboxane milieu observed with ethanol exposure may lead, at least in part, to
      the IUGR which is frequently associated with FAS. Prevention of this effect of
      ethanol on thromboxane production might be a beneficial intervention for FAS.

PMID- 10963941
TI  - Alcohol treatment during lactation produces an advance in the onset of puberty in
      female rats.
AB  - It has been described that alcohol treatment after weaning produces a delay in
      the onset of puberty and a decrease in the body weight of female rats; however,
      during development, there are periods with different sensitivity to endogenous
      and exogenous substances. In this study, two daily doses of 2.5 g/kg of ethanol
      each administered to female pups during days 13-18 of postnatal age produced an
      advance in the age at vaginal opening but induced no effect on the body weight;
      however, the onset of sexual behavior was not advanced. Fertility and
      reproduction measures were not significantly impaired by this treatment. It is
      supported that, in this period, alcohol can produce different effects - even
      opposite to those described in other developmental stages - which seems to
      represent a critical period for alcohol action.

PMID- 10963955
TI  - Inhibition of L-DOPA-Cu(II)-mediated DNA cleavage by bilirubin.
AB  - It has been proposed that considerable DNA damage may be caused by endogenous
      metabolites produced during the body's normal metabolic processes. We have
      previously shown that L-DOPA, in the presence of Cu(II), leads to oxidative DNA
      breakage in vitro. Bilirubin is a degradation product of heme and is considered
      to possess antioxidant properties. In this paper we report that bilirubin
      inhibits L-DOPA-Cu(II)-mediated DNA cleavage to an appreciable extent of 50% at a
      concentration of 50 microM. Bilirubin was also shown to directly quench the
      generation of hydroxyl radicals by L-DOPA-Cu(II) to an extent of 30% at a
      concentration of 20 microM. The results support the putative antioxidant role of
      bilirubin in higher primates.

PMID- 10963957
TI  - Cytotoxic and transforming effects of silica particles with different surface
      properties in Syrian hamster embryo (SHE) cells.
AB  - Several crystalline and amorphous silica dusts (two quartz of natural origin, one
      cristobalite of natural and two of biogenic origin, three amorphous diatomite
      earths and one pyrogenic amorphous silica) were studied in the SHE cell
      transformation assay, in order to compare their cytotoxic and transforming
      potencies and examine the role of the structure and of the state of the surface
      on these effects. Some samples were modified by grinding, etching and heating
      with the aim of establishing relationships between single surface properties and
      biological responses. The results showed that some quartz and cristobalite dusts
      (crystalline) as well as the diatomaceous earths (amorphous), but not the
      pyrogenic amorphous silica, were cytotoxic and induced morphological
      transformation of SHE cells in a concentration-dependent manner. The ranking in
      cytotoxicity was different from that in transforming potency, suggesting two
      separate molecular mechanisms for the two effects. The cytotoxic and transforming
      potencies were different from one dust to another, even among the same structural
      silicas. The type of crystalline structure (quartz vs cristobalite) and the
      crystalline vs biogenic amorphous form did not correlate with cytotoxic or
      transforming potency of silica dusts. Comparison of cellular effects induced by
      original and surface modified samples revealed that several surface
      functionalities modulate cytotoxic and transforming potencies. The cytotoxic
      effects appeared to be related to the distribution and abundance of silanol
      groups and to the presence of trace amounts of iron on the silica surface. Silica
      particles with fractured surfaces and/or iron-active sites, able to generate
      reactive oxygen species, induced SHE cell transformation. The results show that
      the activity of silica at the cellular level is sensitive to the composition and
      structure of surface functionalities and confirm that the biological response to
      silica is a surface originated phenomenon.

PMID- 10963956
TI  - Chromosome damage induced by selenium salts in human peripheral lymphocytes.
AB  - Two inorganic salts of selenium, sodium selenite (Na(2)SeO(3)) and sodium
      selenate (Na(2)SeO(4)), were screened for damage to chromosome and cell division
      following exposure to human lymphocyte cultures. In vitro exposure of human
      peripheral blood lymphocytes to high concentration of two inorganic salts of
      selenium-sodium selenite (2.9 x 10(-5) M) and sodium selenate (2.65 x 10(-5) M)
      was found to be lethal; no blast cells being formed. Lower concentrations of both
      salts, 5.8 x 10(-6) M and 1.06 x 10(-5) M, respectively, were highly mitostatic.
      Lower concentrations of sodium selenite (2.9 x 10(-6) M, 1.16 x 10(-6) M and 2.32
      x 10(-7) M) and sodium selenate (5.3 x 10(-6) M, 2.65 x 10(-6) M and 1.06 x 10(
      6) M), respectively, induced chromosomal aberrations and reduced cell division in
      proportions directly related to the dose. Sodium selenite was considerably more
      clastogenic than sodium selenate.

PMID- 10963958
TI  - Mutagenicity and genotoxicity of sorbic acid-amine reaction products.
AB  - Sorbic acid as well as potassium and calcium sorbate (E202 and E203) are legally
      used as preservatives in numerous processed foods. Owing to its system of
      conjugated double bonds, sorbic acid is likely to undergo a nucleophilic attack,
      which may turn it into mutagenic products. The cyclic derivatives resulting from
      a double addition reaction between sorbic acid and various amines at two
      different temperatures (50 degrees C and 80 degrees C) have been analysed. A
      genotoxicity study has been performed with HeLa cells and plasmid DNA. A
      mutagenesis study has been carried out by using the Ames test. A SOS spot test
      and a cytotoxicity study have been realised as well. The results showed that the
      products involved exhibited neither mutagenic nor genotoxic activities.

PMID- 10963959
TI  - Lavandulylflavonoids: a new class of in vitro apoptogenic agents from Sophora
      flavescens.
AB  - The root of Sophora flavescens has been reported to possess antitumor activity in
      Sarcoma 180, lymphoid leukemia 1210 and melanotic melanoma. We have isolated four
      cytotoxic flavonoids with a lavandulyl side-chain at C8 and tested for their
      effects on human myeloid leukemia HL-60 cells and human hepatocarcinoma HepG2
      cells, in terms of inhibition of proliferation and induction of apoptosis. They
      showed potent antiproliferative effects with IC(50) values from 11.3 microM to
      18.5 microM in HL60 cells and from 13.3 microM to 36. 2 microM in HepG2 cells.
      Treatment of HL-60 cells with the lavandulylflavonoids induced apoptosis in a
      dose-dependent manner. Apoptosis was judged by the detection of DNA fragmentation
      by agarose gel electrophoresis and the degree of apoptosis was quantified by a
      sandwich enzyme immunoassay. The hydration of C4"'C5"' double bond with or
      without C3 hydroxylation caused a complete loss of cytotoxicity. These results
      suggest that the lavandulyl side-chain is essential for the activity of the
      flavonoids isolated from S. flavescens which may be used as cancer
      chemotherapeutic and chemopreventive agents.

PMID- 10963960
TI  - Primary cell cultures of bovine colon epithelium: isolation and cell culture of
      colonocytes.
AB  - Epithelial cells from bovine colon were isolated by mechanical preparation
      combined with an enzymatic digestion from colon specimens derived from freshly
      slaughtered animals. After digestion with collagenase I, the isolated tissue was
      centrifuged on a 2% D-sorbitol gradient to separate epithelial crypts which were
      seeded in collagen I-coated culture flasks. By using colon crypts and omitting
      the seeding of single cells a contamination by fibroblasts was prevented. The
      cells proliferated under the chosen culture conditions and formed monolayer
      cultures which were maintained for several weeks, including subcultivation steps.
      A population doubling time of about 21 hr was estimated in the log phase of the
      corresponding growth curve. During the culture period the cells were
      characterized morphologically and enzymatically. By using antibodies against
      cytokeratine 7 and 13 the isolated cells were identified as cells of epithelial
      origin. Antibodies against vimentin served as negative control. Morphological
      features such as microvilli, desmosomes and tight junctions, which demonstrated
      the ability of the cultured cells to restore an epithelial like monolayer, were
      shown by ultrastructural investigations. The preservation of the secretory
      function of the cultured cells was demonstrated by mucine cytochemistry with
      alcian blue staining. A stable expression of enzyme activities over a period of 6
      days in culture occurred for gamma-glutamyltranspeptidase, acid phosphatase and
      NADH-dehydrogenase activity under the chosen culture conditions. Activity of
      alkaline phosphatase decreased to about 50% of basal value after 6 days in
      culture. Preliminary estimations of the metabolic competence of these cells
      revealed cytochrome P450 1A1-associated EROD activity in freshly isolated cells
      which was stable over 5 days in cultured cells. Then activity decreased
      completely. This culture system with primary epithelial cells from the colon will
      be used further as a model for the colon epithelium in toxicological studies in
      vitro.

PMID- 10963961
TI  - Preliminary evaluation of an in vitro test for assessment of excitotoxicity by
      measurement of early gene (c-fos mRNA) levels.
AB  - Using primary cultures of mouse cerebellar granule cells as an in vitro model
      system, it has been demonstrated that different profiles of temporal expression
      of the c-fos proto-oncogene are observed under non-excitotoxic and excitotoxic
      conditions. A ratio has been derived previously for the steady-state level of c
      fos mRNA after 30 min and 240 min which suggests that a 240 min/30 min ratio of
      greater than 1 correlates with excitotoxicity, whereas a ratio of less than 1
      correlates with a non-excitotoxic outcome. Moreover, a positive correlation is
      seen with abrogation of excitotoxicity in response to selective excitatory amino
      acid receptor antagonists. This test, proposed as a specific biomarker for
      excitotoxicity is undergoing prevalidation. Excitotoxicity is defined as neuronal
      cell death mediated by hyperactivation of glutamate receptor subtypes and
      therefore might be expected to be prevented by selective glutamate receptor
      antagonists. In preliminary evaluation studies, we have conducted work under the
      direction of the European Center for Validation of Alternate Methods (ECVAM)
      using compounds specified by ECVAM that have been subdivided into four groups
      based on known or presumed actions. These groups comprise: Group 1
      endogenous/synthetic excitotoxins; Group 2-environmental, putative excitotoxins;
      Group 3-neurotoxic but non-excitotoxic compounds, and Group 4-non-toxic
      compounds. The results of this study support the proposal that the c-fos mRNA
      time-ratio test is a specific biomarker of excitotoxicity. Just as importantly,
      this test has the potential for application in screening newly-designed EAA
      receptor antagonists in the search for clinically relevant drugs to treat a
      variety of neuropathologies.

PMID- 10963963
TI  - Automated In Vitro Dermal Absorption (AIVDA): predicting skin permeation of
      atrazine with finite and infinite (swimming/bathing) exposure models.
AB  - The Automated In Vitro Dermal Absorption (AIVDA) HPLC method developed in our
      laboratory for finite dose tests was developed further for infinite dose
      swimming/bathing exposure tests and for monitoring skin viability during the
      permeation assay. Skin absorption of the herbicide atrazine was tested under both
      finite and infinite dose conditions and the data compared to that obtained using
      the Bronaugh flow-through cell. Confirmation that skin viability was maintained
      throughout the AIVDA 24-hr infinite dose tests without phenol was obtained using
      a novel Radio-HPLC method that was developed to monitor glycolytic 14C-lactic
      acid formation in 14C-glucose spiked receiver solution. Advantages of the AIVDA
      method (e.g. rapid, sensitive, versatile, cost-effective analysis) together with
      its disadvantages (e.g. need for manual dexterity, lack of receiver albumin,
      compound retention time, limit of sampling interval) are discussed.

PMID- 10963962
TI  - Investigation of the susceptibility of equine autonomic neuronal cell lines,
      clonally derived from the same paravertebral ganglion, to toxic plasma from
      equine dysautonomia (grass sickness) cases.
AB  - In the autonomic nervous system (ANS) of equine grass sickness (GS) cases, some
      neurones show abnormal changes while neighbouring neurones are unaffected. To
      test whether noradrenergic neurones showed variable susceptibility to the GS
      toxin in culture, clonally-derived populations isolated from the same fetal
      thoracic sympathetic chain ganglion were challenged with plasma from GS cases
      previously shown to induce ANS damage when injected into normal horses. During
      the early stages of exposure to toxic plasma, cells within a clonal population
      showed variable susceptibility ranging from no obvious effect to characteristic
      patterns of pathology. However, after 3 days of exposure to toxic plasma all
      cells were killed. Dose response analysis on selected clonal populations showed
      no significant difference in TD(50) values.

PMID- 10963964
TI  - The differential cytotoxicity of methotrexate in rat hepatocyte monolayer and
      spheroid cultures.
AB  - It is important to assess the usefulness of long-term in vitro liver models for
      studying chronic toxicity, since acute assays may not reflect the in vivo
      situation. A potential long-term hepatocyte culture (i.e. liver spheroids) was
      investigated and compared to primary rat hepatocyte monolayer cultures following
      exposure to methotrexate (MTX), a well-documented chronic hepatotoxin. Following
      up to 7 days' treatment with MTX, cultures were morphologically assessed and
      assayed for enzyme leakage, intracellular reduced glutathione (GSH) and adenosine
      triphosphate (ATP). Spheroids maintained higher concentrations of GSH over the 14
      day culture and ATP was maintained, but at a concentration not significantly
      different from monolayer cultures. Treatment of monolayer cultures resulted in
      concentration-related decreases in GSH and ATP, accompanied by enzyme leakage. In
      contrast, only ATP was affected following treatment of spheroids for 7 days.
      Spheroids appeared to be less sensitive to exposure to MTX, when compared with
      monolayer cultures. This may result from the maintenance of cellular functions,
      or from the lack of compound penetration into the three-dimensional spheroid
      structure. Therefore, the usefulness of spheroids to chronic in vitro toxicity
      testing may be limited.

PMID- 10963965
TI  - Treatment of children with simple febrile seizures: the AAP practice parameter.
      American Academy of Pediatrics.
AB  - Febrile seizures are the most common seizure disorder in childhood, occurring in
      2-5% of children. Despite their frequency, there has been little unanimity of
      opinion regarding the need for long-term antiepileptic therapy. As such, the
      American Academy of Pediatrics formulated a subcommittee to study the subject. A
      Practice Parameter was developed that addressed the issue of whether continuous
      or intermittent antiepileptic therapy is necessary for children with simple
      febrile seizures. The committee determined that with the exception of a high rate
      of recurrence, no long-term adverse effects of simple febrile seizures have been
      identified. The risk of developing epilepsy is extremely low and, even in those
      patients who do, there is no evidence that recurrent simple febrile seizures
      produce structural central nervous system damage. Also, there is no evidence that
      recurrent simple febrile seizures cause either learning problems or premature
      death. The committee concluded that although there is the evidence that
      continuous antiepileptic therapy with phenobarbital or valproic acid and
      intermittent therapy with diazepam are effective in reducing the risk of
      recurrence, the potential toxicities associated with antiepileptic therapy
      outweigh the relatively minor risks associated with simple febrile seizures. As
      such, long-term treatment is not recommended.

PMID- 10963966
TI  - Quantitative proton magnetic resonance spectroscopy of focal brain lesions.
AB  - The diagnostic value of single-voxel proton magnetic resonance spectroscopy (2 T,
      stimulated echo acquisition mode, TR = 6,000 ms, TE = 20 ms, 4-5 mL volumes-of
      interest) was assessed for a differentiation of focal brain lesions of unknown
      etiology in 17 patients 1-14 years of age. Absolute metabolite concentrations
      were compared with age-matched control subjects and an individual control region.
      Most of the brain tumors were characterized by strongly reduced total N
      acetylaspartyl compounds and marked increases of myo-inositol and choline
      containing compounds, consistent with a lack of neuroaxonal tissue and a
      proliferation of glial cells. Lactate was elevated in only four patients. When
      using this pattern for a metabolic discrimination of brain tumors from other
      focal lesions, proton spectroscopy correctly identified 14 of 17 abnormalities,
      as confirmed by histologic examination after neurosurgical intervention. One
      false-positive tumor diagnosis was a severe reactive gliosis mimicking a typical
      tumor spectrum. Two inconclusive cases comprised an astrocytoma with moderately
      elevated myo-inositol but reduced choline-containing compounds and a patient with
      an abscess leading to a marked reduction of all metabolites but strong
      contributions from mobile lipids. In summary, quantitative proton spectroscopy
      has considerable clinical value for preoperative characterization of focal brain
      lesions.

PMID- 10963967
TI  - Electroretinography is necessary for spasmus nutans diagnosis.
AB  - The purpose of the present study was to determine whether that which clinically
      appeared to be spasmus nutans could actually represent retinal sensory deficits
      diagnosable by electroretinography. Eight patients clinically thought to have
      spasmus nutans underwent electroretinography according to international
      standards. Five had normal electroretinograms and represented cases of true
      spasmus nutans. Three patients had abnormal electroretinograms, indicating that
      they did not have spasmus nutans. The clinical findings used to diagnose spasmus
      nutans can be simulated by retinal dystrophies. A normal electroretinogram is
      needed to confirm the diagnosis of spasmus nutans.

PMID- 10963968
TI  - Downregulation of glutamate receptor subunit 2(3) in subependymal giant-cell
      tumor.
AB  - Immunohistochemical techniques were used to investigate the expression of
      glutamate receptor (GluR) subunits in samples of brain resected from children
      with and without tuberous sclerosis, using antibody to an epitope common to GluR
      subunits 2 and 3 [2(3)]. Our purpose was to characterize the phenotype of balloon
      cells in cortical tubers and tumor cells in subependymal giant-cell tumors. In
      cortical tubers, GluR 2(3) was expressed in the processes and cell bodies of
      balloon cells, demonstrating consistent immunoreactivity to vimentin. In
      subependymal giant-cell tumors, tumor cells also exhibited consistent
      immunoreactivity to vimentin but only faint immunoreactivity to GluR 2(3). The
      reason for the expression of subunit 2(3) in tubers but not in subependymal giant
      cell tumors remains unknown. However, if one assumes that the presence of subunit
      2 substantially reduces calcium conductance through alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid channel and maintains intracellular calcium
      homeostasis, one could speculate that downregulation of subunit 2(3) in tumor
      cells could result in increased calcium flux into these cells, causing
      tumorigenesis. Another explanation may be that receptor subunits cannot be
      produced sufficiently in tumor cells. Moreover, the pathogenetic pathways between
      balloon and giant-cells are distinctly different, despite the similarity in their
      phenotypical pathologic features.

PMID- 10963970
TI  - Vertigo is an underestimated symptom of ocular disorders: dizzy children do not
      always need MRI.
AB  - Vertigo, instability, dizziness, or equilibrium disorders are not usually
      considered as consequences of ophthalmologic problems. We present data indicating
      that ocular disorders can be responsible for these symptoms in children. In a
      population of 523 pediatric patients with vertigo or disequilibrium and referred
      for vestibular testing in our otolaryngology department during a 5-year period,
      27 children presented with normal vestibular and somatic neurologic examinations
      but with ophthalmologic disorders (vergence insufficiency or latent strabismus
      with binocular vision in 70% and anisometropia in 41%). These patients
      represented 24% of all vergence insufficiencies detected and 4% of all orthoptic
      examinations performed in the pediatric ophthalmology department. These ocular
      abnormalities were considered to be the initial cause of the problems. In two
      thirds of these patients the symptoms were completely resolved by simple
      ophthalmologic treatment. No other additional tests, such as magnetic resonance
      imaging, were required. Therefore we propose that every child complaining of
      vertigo or dizziness but with normal clinical somatic neurologic and vestibular
      examinations should have a complete ophthalmologic examination before additional,
      more costly, investigations. This should lead to better screening and more
      appropriate care of ocular disorders in children and avoid unnecessary magnetic
      resonance imaging.

PMID- 10963969
TI  - Glutamate transporters in neonatal cerebellar subarachnoid hemorrhage.
AB  - We have previously described the immunoreactivities of glutamate transporters,
      EAAT4 and GLAST, in the developing human cerebellum. In the present report, we
      demonstrate the different expression of EAAT4 and GLAST in the pathologic
      condition, neonatal subarachnoid hemorrhage. EAAT4 and GLAST were
      characteristically disturbed in the cerebellar cortices beneath the subarachnoid
      hemorrhage. In preterm infants with subarachnoid hemorrhage the decrease in EAAT4
      immunoreactivity was more prominent than in term infants, and GLAST
      immunoreactivity in the inner granular cell layer decreased and reappeared later
      than in term infants with subarachnoid hemorrhage. Although Bergmann's glia
      removes glutamate from the extracellular space surrounding Purkinje cells in the
      early stage of hypoxic-ischemic brain damage, the reaction of EAAT4 and GLAST in
      the cerebellar cortex under the subarachnoid hemorrhage was decreased, and
      immature glia had a delayed reaction. These characteristics of glutamate
      transporters in immature cells may lead to cell death and olivocerebellar
      degeneration.

PMID- 10963971
TI  - Mitochondrial activity in Pompe's disease.
AB  - Mitochondrial oxidative metabolism was examined in two infants with Pompe's
      disease. The clinical diagnosis was confirmed by the demonstration of
      intralysosomal glycogen accumulation and a deficiency of acid alpha-D-glucosidase
      in muscle biopsies. Light and electron microscopy studies demonstrated a normal
      number of mitochondria with normal ultrastructure. Spectrophotometric
      measurements revealed that the specific activities of citrate synthase and the
      partial reactions of electron transport were markedly elevated in the skeletal
      muscle homogenates prepared from both infants with Pompe's disease when
      calculated as micromoles per minute per gram wet weight of tissue. However, when
      respiratory chain enzyme activities were expressed relative to citrate synthase
      as a marker mitochondrial enzyme, a different pattern emerged, in which all Pompe
      muscle respiratory enzymes, except complex IV, were decreased relative to control
      subjects. These observations demonstrate that caution should be exercised when
      analyzing and interpreting data obtained from tissue homogenates in general and,
      in particular, in those prepared from tissues in which the wet weight of tissue
      may be altered, for example, by pathologic accumulation of carbohydrate or lipid.

PMID- 10963972
TI  - Predictive value of acetylcholine stimulation testing for oligohidrosis caused by
      zonisamide.
AB  - We studied 16 patients for whom zonisamide was newly prescribed. Acetylcholine
      stimulation testing was performed about 1 month after zonisamide was initiated.
      Oligohidrosis occurred in none of the four with a normal response and in four of
      the 12 with a decreased response. Acetylcholine stimulation testing predicted
      oligohidrosis with a sensitivity of 1 and a false-positive rate of 0.67. The
      acetylcholine stimulation test was sensitive in detecting oligohidrosis caused by
      zonisamide, although the false-positive rate was high.

PMID- 10963973
TI  - Antiphospholipid- associated recurrent chorea and ballism in a child with
      cerebral palsy.
AB  - We present the case of a 9-year-old female with cerebral palsy and repeated
      episodes of ballism associated with antiphospholipid and anticardiolipin
      antibodies. She was treated unsuccessfully with varying medications, including
      neuroleptics, anticholinergics, antiepileptics, dopamine, dopamine agonists, and
      monoamine oxidase inhibitors. Intravenous immunoglobulin and corticosteroids led
      to resolution of the movements. We postulate an immune mechanism of disease for
      ballism associated with antiphospholipid and anticardiolipin antibodies.

PMID- 10963974
TI  - Paraparesis after lumbar puncture in a male with leukemia.
AB  - A diagnostic lumbar puncture was performed in a 12-year-old male with acute
      lymphoblastic leukemia. Because of thrombocytopenia (platelet count
      42,000/mm(3)), a platelet transfusion was given immediately before the lumbar
      puncture. However, the platelet count was not re-examined. The patient developed
      progressive paraparesis shortly after the lumbar puncture. Magnetic resonance
      imaging revealed an extensive spinal subdural hematoma from the T2 to S2 level.
      This case report illustrates the sometimes dramatic consequences of lumbar
      puncture in patients with childhood leukemia. Guidelines for the examination of
      the platelet count and correction of thrombocytopenia before lumbar puncture are
      discussed.

PMID- 10963975
TI  - Non-Hodgkin's lymphoma of the uterus and CNS.
AB  - We report a case of a non-Hodgkin's lymphoma of the uterus and central nervous
      system in an 8-year-old female. The neurologic signs included blurred vision,
      neck stiffness, and walking difficulties but no abdominal problems. She
      deteriorated further, and repeated lumbar punctures revealed the presence of
      malignant cells in the cerebrospinal fluid. A repeated ultrasound scan of the
      abdomen demonstrated a markedly enlarged uterus. Biopsy revealed B-cell non
      Hodgkin's lymphoma. Treatment according to the Berlin-Frankfurt-Munster protocol
      was initiated, but she developed hyperventilation syndrome and required
      mechanical ventilation. Her condition improved after 1 week but then deteriorated
      again, and despite additional chemotherapy she developed myelosuppression and
      septicemia with multiresistant Klebsiella pneumoniae and eventually died 13
      months after her first admission to the hospital. No clinical or laboratory signs
      of relapse were evident at the time of death.

PMID- 10963976
TI  - Asymmetric sweating in a child with multiple sclerosis.
AB  - A 10-year-old male with multiple sclerosis complained of excessive sweating on
      the right side of the forehead and shoulder on relapse 3 months after the onset
      of multiple sclerosis. Because the neurologic evaluation revealed no
      abnormalities in the sudomotor function, it is likely that the hyperhidrosis
      resulted from a lesion in the central or preganglionic sympathetic nervous
      system. Magnetic resonance imaging demonstrated a high-intensity lesion involving
      the left hypothalamus on T(2)-weighted imaging. Thus hypothalamic involvement
      might be the reason for the hyperhidrosis in this patient.

PMID- 10963977
TI  - Eyelid fluttering accompanying diffuse epileptic EEG induced by eye closure.
AB  - A 13-year-old male exhibited the following clinical and electroencephalographic
      (EEG) manifestations. He exhibited marked photosensitivity on EEG from the first
      visit at 9 years of age until 11 years of age and had an episode of television
      epilepsy at 9 years of age. Generalized epileptic EEG findings followed by marked
      eyelid fluttering, induced by eye closure in a bright room that lasted until the
      eyes were opened, but not by eye closure in a dark room, were first noticed at 11
      years of age. A generalized epileptiform EEG was not induced when the light was
      turned off if the eyes were kept open. His photosensitivity disappeared by 12
      years of age, but the eyelid fluttering with epileptic EEG induced by eye closure
      was still present at 13 years of age. The epileptic EEG was thought to be induced
      by a modification of the retinal input on eye closure, not by mechanical or
      sensory stimulation on eye closure or fixation-off sensitivity. In addition, in
      this patient a change from photosensitive to eye closure-sensitive epilepsy
      seemed to occur, which suggests that the correlation between the epileptic EEG
      and retinal input are complex.

PMID- 10963978
TI  - Prolonged survival with hydranencephaly: report of two patients and literature
      review.
AB  - Infants with hydranencephaly are presumed to have a reduced life expectancy, with
      a survival of several weeks to months. Rarely, patients with prolonged survival
      have been reported, but these infants may have had other neurologic conditions
      that mimicked hydranencephaly, such as massive hydrocephalus or
      holoprosencephaly. We report two infants with prenatally acquired hydranencephaly
      who survived for 66 and 24 months. We reviewed published reports to ascertain the
      clinical and laboratory features associated with survival of more than 6 months.
      This review demonstrates that prolonged survival up to 19 years can occur with
      hydranencephaly, even without rostral brain regions, with isoelectric
      electroencephalograms, and with absent-evoked potentials. Finally, the ethical
      aspects of these findings, as they relate to anencephaly and organ
      transplantation, are discussed.

PMID- 10963979
TI  - Mutation analysis of 16S rRNA in patients with Rett syndrome.
AB  - Rett syndrome (RTT) is a progressive neurodevelopmental disorder that affects one
      in 10,000-15,000 females. RTT is mainly sporadic; familial cases have an
      estimated frequency of less than 1%. Before the recent identification of de novo
      dominant mutations in the X-linked MECP2 gene, many other hypotheses had been
      proposed to explain the particular pattern of inheritance and the phenotypic
      expression of the disease. The involvement of mitochondrial DNA had been
      investigated because of the structural and functional mitochondrial abnormalities
      evident in the patients. In 1997 the finding of mutations at 16S rRNA in several
      affected RTT females and their mothers was reported, suggesting that
      mitochondrial DNA might play a key role in the pathogenesis of RTT. To
      investigate the relevance of such mutations, we used the same methodologic
      approach to analyze RTT mitochondrial DNA in our series. No 16S rRNA alterations
      were evident in 27 Spanish patients with classic RTT.

PMID- 10963981
TI  - Letter from the editor

PMID- 10963980
TI  - Traumatic spinal epidural hematoma of a 10-month-old male: a clinical note.
AB  - Traumatic spinal epidural hematoma (TSEH) is rare in children. Only three cases
      of TSEH were documented in the pediatric literature. This clinical note presents
      an infant with TSEH but no risk factors. Without magnetic resonance imaging
      examination, children with TSEH and minor symptoms may be missed and under
      reported. Signs such as irritability and neck pain should alert the clinician to
      consider TSEH and the need for urgent magnetic resonance imaging of the spine for
      early diagnosis and treatment to minimize morbidity.

PMID- 10963982
TI  - Cerebral perfusion abnormalities in abstinent cocaine abusers: a perfusion MRI
      and SPECT study.
AB  - Nuclear medicine studies found decreased regional cerebral blood flow (rCBF) in
      the cortex and deep gray matter of cocaine users. Perfusion magnetic resonance
      imaging (MRI), a non-radioactive technique, has not been applied to evaluate
      persistent rCBF abnormalities. Twenty-five abstinent cocaine users and 15 healthy
      subjects without a history of drug use were examined with perfusion MRI, using
      dynamic bolus-tracking, and single photon emission computed tomography (SPECT),
      using 133Xe-calibrated 99mTc-HMPAO. After coregistration of SPECT with MRI, the
      relative rCBF (from perfusion MRI and SPECT) and absolute rCBF (from SPECT) were
      determined in 10 brain regions in each hemisphere. There was a statistically
      significant interaction between drug use and brain region on SPECT alone
      (relative and absolute rCBF), and on SPECT and perfusion MRI combined, but not on
      perfusion MRI alone. There also was a significant interaction among gender, drug
      use, and brain region. Compared to the control subjects, cocaine users showed
      increased rCBF in the frontal white matter (+8.6%, P=0.02) and in the globus
      pallidus (+6.3%, P=0.05), and decreased rCBF in the putamen (-3.9%, P=0.04) and
      the temporal cortex (-2.4%, P=0.02). SPECT and perfusion MRI detect a regional
      pattern of rCBF abnormalities in cocaine users that is consistent across the two
      methods. The hypoperfusion in the cortex and deep gray matter of the cocaine
      users is consistent with previous results. The increased rCBF in the white matter
      of cocaine users may be due to the presence of reactive glia.

PMID- 10963983
TI  - Temporal lobe volume in panic disorder--a quantitative magnetic resonance imaging
      study.
AB  - Although previous studies have used magnetic resonance imaging (MRI) to
      demonstrate qualitative abnormalities of the temporal lobes in patients with
      panic disorder, no study to date has applied quantitative volumetric methods to
      evaluate brain changes in panic disorder. The purpose of this study was to
      measure the volume of the temporal lobe and the hippocampus in patients with
      panic disorder and healthy control subjects using quantitative MRI measures. The
      volume of the temporal lobe, hippocampus and whole brain was measured in 13
      patients with panic disorder and 14 healthy subjects. The mean volume of the left
      and right temporal lobes was significantly smaller in panic disorder compared to
      healthy subjects (16770+/-909 mm(3) vs. 18343+/-1740 mm(3)). This result was
      significant after controlling for differences in whole brain volume. There was no
      significant difference in volume of the hippocampus between patients and control
      subjects. These findings are consistent with smaller temporal lobe volume in
      panic disorder despite normal hippocampal volume.

PMID- 10963984
TI  - Ventricular enlargement in schizophrenia spectrum patients with prodromal
      symptoms of obsessive-compulsive disorder.
AB  - We hypothesized that male patients with schizophrenia spectrum disorders who have
      prodromal symptoms of obsessive-compulsive disorder (OCD) have ventricular
      enlargement compared with non-psychotic OCD patients, and that the difference in
      the ventricular size would offer a clue to the early detection of schizophrenia
      spectrum disorders. The ventricle-brain ratios (VBRs) in eight male patients with
      schizophrenia or schizotypal personality disorder (SPD) who had prodromal
      symptoms of OCD were compared with eight male patients with non-psychotic OCD and
      14 normal male comparison subjects using three-dimensional magnetic resonance
      imaging (MRI). The VBR of the schizophrenia spectrum group was significantly
      larger than those of the OCD group or comparison subjects. Even the minimum VBR
      in the schizophrenia spectrum group was larger than the maximum VBR in the OCD
      group. These results may suggest the usefulness of three-dimensional MRI for
      early detection of patients with schizophrenia spectrum disorders who manifest
      OCD symptoms early in the course of the illness.

PMID- 10963985
TI  - Evidence of a smaller left hippocampus and left temporal horn in both patients
      with first episode schizophrenia and normal control subjects.
AB  - Findings from cerebral magnetic resonance imaging (MRI) studies in schizophrenia
      indicating temporal lobe involvement have been inconsistent and controversial. In
      a prospective study, we quantified the volumes of temporal lobe structures in 20
      male patients with first episode schizophrenia (FES; mean+/-S.D.=27.4+/-4. 8
      years) and 20 healthy age-matched male control subjects (27.7+/-3. 1 years).
      Measurements were performed on contiguous 2.2-mm coronal MRI slices, which
      included, as well as the temporal lobe, the amygdala, the hippocampal formation,
      and the temporal horn of the lateral ventricle. The definition of the borders of
      the structures relied on measurement guidelines derived from mutual comparisons
      of MRI and histological data. The definition of the hippocampus-amygdala
      interface was also validated in a correlated triplanar display. We did not detect
      any significant volume reductions of the measured structures in the FES group, as
      compared with healthy control subjects, on either side. Comparisons within
      groups, however, revealed that in both the patients and the healthy volunteers
      the hippocampal formations showed a significant right-sided bias (+9%, P=0.004,
      in the FES group; +12%, P=0.0003 in the control subjects). A significant volume
      difference in favor of the right hemisphere was also observed in the temporal
      horns of the lateral ventricles (+17%, P=0.02 in the patients with FES; +34%,
      P=0. 003, in the control group). There was only a nonsignificant trend for a
      larger temporal horn on the left side in patients with schizophrenia as compared
      with the control subjects. Our findings do not indicate a loss or reversal of the
      normal volume asymmetry pattern in the FES group.

PMID- 10963987
TI  - Proceedings of the XVII Meeting of the Federation of the European Connective
      Tissue Society. Patras, Greece, 1-5 July 2000.

PMID- 10963986
TI  - Mixed models and multiple comparisons in analysis of human neurochemical maps.
AB  - Examination of brain regional neurochemistry in disease states reveals
      differences among brain regions. Knowing where alterations in brain function are
      located is crucial to understanding the disease effect. The anatomical
      distribution of neurotransmitter receptors is now often studied using
      quantitative autoradiography, but the large number of brain regions involved
      raises serious problems for statistical analysis of such data. Due to the
      dependence among the subjects in case control designs, statistical analysis based
      on a 'mixed model' is useful. Such an analysis is illustrated using a small
      autoradiographic data set. The Bonferroni method, the method of Holm, and two
      'False Discovery Rate'-controlling methods for adjusting P-values for multiple
      comparisons are compared.

PMID- 10963988
TI  - What are oligomerization domains good for?
AB  - Collagen triple helices, coiled coils and other oligomerization domains mediate
      the subunit assembly of a large number of proteins. Oligomerization leads to
      functional advantages of multivalency and high binding strength, increased
      structure stabilization and combined functions of different domains. These
      features seen in naturally occurring proteins can be engineered by protein design
      by combining oligomerization domains with functional domains.

PMID- 10963989
TI  - The EMILIN protein family.
AB  - The EMILINs are a new family of glycoproteins of the extracellular matrix. The
      prototype of this family is the chicken EMILIN that was originally identified in
      extracts of aortas; it was then found to be widely distributed in several tissues
      associated with elastin and localized at the interface between amorphous elastin
      and microfibrils. Based on peptide sequences, chicken and human cDNAs coding for
      EMILIN were isolated by RT/PCR by screening kidney and heart cDNA libraries. By
      using a C-terminal fragment of human EMILIN-1 as a bait in the yeast two-hybrid
      system, a second family member, EMILIN-2, has also been isolated. EMILINs are
      characterized by a C-terminal gC1q globular domain, a short collagenous sequence,
      a long coiled-coil region and a new cysteine-rich N-terminal domain that can be
      considered a hallmark of the family being present also in multimerin. The gene
      for EMILIN-1 was mapped on chromosome 2p23 overlapping with the promoter region
      of the ketohexokinase gene. The gC1q domain of EMILIN-1 can form relatively
      stable and compact homotrimers and this association is then followed by a
      multimeric assembly of disulfide-bonded protomers. Recombinant EMILIN-1 purified
      from the supernatant of 293 cells represents a very efficient ligand for cell
      adhesion of several cell types.

PMID- 10963990
TI  - Role of heparan sulfate proteoglycans in cell-cell signaling in Drosophila.
AB  - Heparan sulfate proteoglycans (HSPGs) are abundant molecules associated with the
      cell surface and extracellular matrix, and consist of a protein core to which
      heparan sulfate (HS) glycosaminoglycan (GAG) chains are attached. Although these
      molecules have been the focus of intense biochemical studies in vitro, their
      biological functions in vivo were unclear until recently. We have undertaken an
      in vivo functional study of HSPGs in Drosophila. Our studies, as well as others,
      demonstrate the critical roles of HSPGs in several major signaling pathways,
      including ibroblast growth factor (FGF), Wnt, Hedgehog (Hh) and TGF-beta. Our
      results also suggest that specific HS GAG chain modifications, as well as
      specific HSPG protein cores, are involved in specific signaling pathways.

PMID- 10963991
TI  - Structure and function of laminin LG modules.
AB  - Laminin G domain-like (LG) modules of approximately 180-200 residues are found in
      a number of extracellular and receptor proteins and often are present in tandem
      arrays. LG modules are implicated in interactions with cellular receptors
      (integrins, alpha-dystroglycan), sulfated carbohydrates and other extracellular
      ligands. The recently determined crystal structures of LG modules of the laminin
      alpha2 chain reveal a compact beta sandwich fold and identify a novel calcium
      binding site. Binding epitopes for heparin, sulfatides and alpha-dystroglycan
      have been mapped by site-directed mutagenesis and show considerable overlap. The
      epitopes are located in surface loops around the calcium site, which in other
      proteins (agrin, neurexins) are modified by alternative splicing. Efficient
      ligand binding often requires LG modules to be present in tandem. The close
      proximity of the N- and C-termini in the LG module, as well as a unique link
      region between laminin LG3 and LG4, impose certain constraints on the arrangement
      of LG tandems. Further modifications may be introduced by proteolytic processing
      of laminin G domains, which is known to occur in the alpha2, alpha3 and alpha4
      chains.

PMID- 10963992
TI  - The collagen receptor integrins have distinct ligand recognition and signaling
      functions.
AB  - Distinct collagen subtypes are recognized by specific cell surface receptors. Two
      of the best known collagen receptors are members of the integrin family and are
      named alpha1beta1 and alpha2beta1. Integrin alpha1beta1 is abundant on smooth
      muscle cells, whereas the alpha2beta1 integrin is the major collagen receptor on
      epithelial cells and platelets. Many cell types, such as fibroblasts,
      osteoblasts, chondrocytes, endothelial cells, and lymphocytes may concomitantly
      express both of the receptors. We have studied the cell biology of these
      integrins at two levels. First, we have analyzed their ligand binding mechanism
      and specificity. Second, we have studied their signaling function inside three
      dimensional collagen gels. This mini-review summarizes our most recent results.
      In conclusion, our data indicate that alpha1beta1 and alpha2beta1 integrins have
      differences in their ligand binding specificity. Furthermore, the two receptors
      are connected to distinct signaling pathways and their ligation may lead to
      opposite cellular responses.

PMID- 10963993
TI  - Fibroblast-matrix interactions in wound healing and fibrosis.
AB  - The regulation of matrix deposition is a key event in many physiological and
      pathological situations. It involves the activity of mediators in autocrine and
      paracrine fashions and the contact of cells with the surrounding extracellular
      matrix as well. The tightly regulated balance of both mechanisms guarantees rapid
      and adaptive cellular responses to meet changes in the biological requirements of
      the environment. Disturbances lead to wound healing defects or the development of
      fibrosis. The molecular mechanisms for these regulatory events are only partially
      understood, but involve the activity of integrins and a structural continuum of
      extracellular matrix-receptor-cytoskeleton-nucleus for transfer of information
      and the regulation of activated genes.

PMID- 10963994
TI  - Mechanisms involved in cartilage proteoglycan catabolism.
AB  - The increased catabolism of the cartilage proteoglycan aggrecan is a principal
      pathological process which leads to the degeneration of articular cartilage in
      arthritic joint diseases. The consequent loss of sulphated glycosaminoglycans,
      which are intrinsic components of the aggrecan molecule, compromises both the
      functional and structural integrity of the cartilage matrix and ultimately
      renders the tissue incapable of resisting the compressive loads applied during
      joint articulation. Over time, this process leads to irreversible cartilage
      erosion. In situ degradation of aggrecan is a proteolytic process involving
      cleavage at specific peptide bonds located within the core protein. The most well
      characterised enzymatic activities contributing to this process are engendered by
      zinc-dependent metalloproteinases. In vitro aggrecanolysis by matrix
      metalloproteinases (MMPs) has been widely studied; however, it is now well
      recognised that the principal proteinases responsible for aggrecan degradation in
      situ in articular cartilage are the aggrecanases, two recently identified
      isoforms of which are members of the 'A Disintegrin And Metalloproteinase with
      Thrombospondin motifs' (ADAMTS) gene family. In this review we have described:
      (i) the development of monoclonal antibody technologies to identify catabolic
      neoepitopes on aggrecan degradation products; (ii) the use of such neoepitope
      antibodies in studies designed to characterise and identify the enzymes
      responsible for cartilage aggrecan metabolism; (iii) the biochemical properties
      of soluble cartilage aggrecanase(s) and their differential expression in situ;
      and (iv) model culture systems for studying cartilage aggrecan catabolism. These
      studies have clearly established that 'aggrecanase(s)' is primarily responsible
      for the catabolism and loss of aggrecan from articular cartilage in the early
      stages of arthritic joint diseases that precede overt collagen catabolism and
      disruption of the tissue integrity. At later stages, when collagen catabolism is
      occurring, there is evidence for MMP-mediated degradation of the small proportion
      of aggrecan remaining in the tissue, but this occurs independently of continued
      aggrecanase activity. Furthermore, the catabolism of link proteins by MMPs is
      also initiated when overt collagen degradation is evident.

PMID- 10963995
TI  - Effects of thrombin/thrombosis in angiogenesis and tumour progression.
AB  - Laboratory, histopathological, pharmacological and clinical evidence support the
      notion that a systemic activation of blood coagulation is often present in cancer
      patients. On the other hand, epidemiological studies provide evidence of an
      increased risk of cancer diagnosis following primary thromboembolism. Moreover,
      the metastatic ability of human breast cancer cells is correlated with the number
      of thrombin receptors of these cells, and thrombin treatment of B16 melanoma
      cells dramatically increases the number of lung metastases in rats. We have
      proposed that these tumour-promoting effects of thrombin can be explained by the
      ability of thrombin to activate angiogenesis, an essential requirement for tumour
      progression. Many of the cellular events involved in the angiogenic cascade can
      be activated by thrombin. At the molecular level, brief exposure of endothelial
      cells to thrombin causes an upregulation of the receptors (KDR and Flt-1) of
      VEGF, the key angiogenic mediator. This results in a synergistic effect of
      thrombin and VEGF in the activation of angiogenesis. In addition, thrombin
      activates cancer cells to secrete VEGF, thus causing a mutual stimulation between
      EC and CA cells. Cancer cells exposed to thrombin secrete metalloproteinase 92 KD
      and overexpress the integrin a(v)b(3), all of which are involved in tumour
      metastasis.

PMID- 10963996
TI  - Tissue engineering of vascular grafts.
AB  - The challenge of tissue engineering blood vessels with the mechanical properties
      of native vessels, and with the anti-thrombotic properties required is immense.
      Recent advances, however, indicate that the goal of providing a tissue-engineered
      vascular graft that will remain patent in vivo for substantial periods of time,
      is achievable. For instance, collagen gels have been used to fabricate a tissue
      in vitro that is representative of a native vessel: an acellular collagen tubular
      structure, when implanted as a vascular graft, was able to function, and to
      become populated with host cells. A completely cellular approach culturing cells
      into tissue sheets and wrapping these around a mandel was able to form a layered
      tubular structure with impressive strength. Culture of cells onto a biodegradable
      scaffold within a dynamic bioreactor, generated a tissue-engineered vascular
      graft with substantial stiffness and, when lined with endothelial cells, was able
      to remain patent for up to 4 weeks in vivo. In our experiments, use of a non
      degradable polyurethane scaffold and culture with smooth muscle cells generated a
      construct with mechanical properties similar to native vessels. This composite
      tissue engineered vascular graft with an endothelial layer formed using fluid
      shear stress to align the endothelial cells, was able to remain patent with an
      neointima for up to 4 weeks. These results show that tissue engineering of
      vascular grafts has true potential for application in the clinical situation.

PMID- 10963997
TI  - Tip-mediated fusion involving unipolar collagen fibrils accounts for rapid fibril
      elongation, the occurrence of fibrillar branched networks in skin and the paucity
      of collagen fibril ends in vertebrates.
AB  - Collagen fibrils are the principal source of mechanical strength of connective
      tissues such as tendon, skin, cornea, cartilage and bone. The ability of these
      tissues to withstand tensile forces is directly attributable to the length and
      diameter of the fibrils, and to interactions between individual fibrils. Although
      electron microscopy studies have provided information on fibril diameters, little
      is known about the length of fibrils in tissue and how fibrils interact with each
      other. The question of fibril length has been difficult to address because fibril
      ends are rarely observed in cross-sections of tissue. The paucity of fibril ends,
      or tips, has led to controversy about how long individual fibrils might be and
      how the fibrils grow in length and diameter. This review describes recent
      discoveries that are relevant to these questions. We now know that vertebrate
      collagen fibrils are synthesised as short (1-3 microm) early fibrils that fuse
      end-to-end in young tissues to generate very long fibrils. The diameter of the
      final fibril is determined by the diameter of the collagen early fibrils. During
      a late stage of tissue assembly fibril tips fuse to fibril shafts to generate
      branched networks. Of direct relevance to fibril fusion is the fact that collagen
      fibrils can be unipolar or bipolar, depending on the orientation of collagen
      molecules in the fibril. Fusion relies on: (1) specific molecular interactions at
      the carboxyl terminal ends of unipolar collagen fibrils; and (2) the insulator
      function of small proteoglycans to shield the surfaces of fibrils from
      inappropriate fusion reactions. The fusion of tips to shafts to produce branched
      networks of collagen fibrils is an elegant mechanism to increase the mechanical
      strength of tissues and provides an explanation for the paucity of fibril tips in
      older tissue.

PMID- 10963998
TI  - Biosynthesis of decorin and glypican.
AB  - Decorin and glypican are two examples of exclusively chondroitin/dermatan sulfate
      and heparan sulfate-substituted proteoglycans, respectively. Decorin is a
      secretory product, whereas glypican is linked to membrane lipids via a glycosyl
      phosphatidyl-inositol (GPI) anchor. The nascent decorin protein enters the lumen
      of the ER, whereas that of glypican is transferred to the preformed GPI-anchors.
      Both types of glycosaminoglycuronans are initiated on Ser residues located in
      special consensus sequences, and the first glycosylation steps constitute a
      common pathway: the generation of the linkage region GlcA-Gal-Gal-Xyl-Ser<. The
      nature of the enzymes involved will be reviewed with special emphasis on the
      recently discovered transient 2-phosphorylation of xylose. The initiation enzymes
      (betaGalNAc-T1 and alphaGlcNAc-T1) then use these tetrasaccharide primers for
      either chondroitin or heparan sulfate assembly. The selection mechanism is not
      yet fully understood. The transferases that form the linkage-region and add the
      first hexosamine, as well as the uronosyl C-5 epimerases, appear to be products
      of single genes, but many isoforms of the copolymerases and sulfotransferases
      forming the repetitive part of the glycan chains are currently being discovered.
      When these enzymes work together, the fine structure of the
      glycosaminoglycuronans appears to be generated through the selective expression
      of isoforms that only operate in certain structural contexts. During heparan
      sulfate assembly, generation of GlcNH(2) as a permanent feature is now well
      recognised. Studies on glypican-1 glycoforms that recycle suggest that heparan
      sulfate chains are degraded by endoheparanase at or near GlcNH(2) residues,
      followed by deaminative cleavage catalysed by NO-derived nitrite. Chain-truncated
      glypican-1 can serve as a precursor for the reformation of a proteoglycan with
      full-size chains. Regulation of biosynthesis can be exercised at several levels,
      such as expression of the core protein, selection for chondroitin or heparan
      sulfate assembly, expression of modifying enzymes, and degradation and
      remodelling. Cytokines, growth factors, NO and polyamines may have regulatory
      roles.

PMID- 10963999
TI  - The female condom and STDs: design of a community intervention trial.
AB  - OBJECTIVES: The main purpose of this study is to compare sexually transmitted
      disease (STD) prevalence in cohorts of women with and without access to female
      condoms. METHODS: Six matched pairs of communities were identified from Kenya
      tea, coffee and flower plantations. One community within each pair was randomly
      selected to receive the female condom intervention. Approximately 160 eligible
      women were enrolled at each site. Female condom communities underwent an
      education program on use of female and male condoms and STDs, comprising group
      meetings, puppetry and other folk media, and training of clinic service providers
      and community outreach workers. Control communities received similar information
      on use of male condoms (freely available at all sites). At baseline, participants
      were tested for cervical gonorrhea and chlamydia and vaginal trichomoniasis, to
      be repeated at 6 and 12 months. The study has 80% power to detect a 10%
      prevalence difference, assuming an aggregate STD prevalence of 20% with 25% loss
      to follow-up and intracluster correlation of 0.03. RESULTS: Among 1929 women at
      baseline, the mean age was 33.1 years; 78% had never used a male condom. The
      prevalences of gonorrhea, chlamydia and trichomoniasis were 2.6%, 3. 2% and
      20.4%, respectively (23.9% overall). The intracluster correlation based on these
      data was near zero. CONCLUSIONS: Comparable pairs of study sites have been
      selected. STD prevalence is sufficiently high, and the variation between sites is
      acceptably low. The study is feasible as designed.

PMID- 10964000
TI  - A prospective study of alcohol consumption and cataract extraction among U.S.
      women.
AB  - PURPOSE: Alcohol consumption has been implicated in the pathogenesis of cataract
      in some, but not all analytic studies. To date, no prospective analysis of the
      relationship between alcohol consumption and cataract has been conducted in
      women. METHODS: We examined the association between alcohol consumption and
      cataract extraction in a prospective cohort of female registered nurses. In 1980,
      50,461 women were included and others were added as they became 45 years of age
      for a total of 77,466 women. Information on alcohol consumption and incidence of
      senile cataract extraction was ascertained during 12 years of follow-up with
      biennial questionnaires. RESULTS: We observed 1468 cases of cataract extraction
      in 761,036 person-years of follow-up. Compared to nondrinkers, those consuming
      alcohol were not at increased risk of cataract, even up to 25 grams or more per
      day (2 or more drinks). Results remained unchanged after controlling for cataract
      risk factors including cigarette smoking, body mass index, and diabetes. When
      risk was examined for specific cataract subtypes only, those in the highest
      category of consumption had a multivariate relative risk of 1.10 for nuclear
      cataracts and 1.50 for posterior subcapsular cataracts only. CONCLUSIONS: These
      prospective data suggest that there is no substantial overall increased risk of
      senile cataract due to alcohol intake. The possibility that alcohol consumption
      leads to a modest increased risk of posterior subcapsular type opacities
      requiring extraction merits further exploration.

PMID- 10964001
TI  - Validity of nutrient estimates by food frequency questionnaires based either on
      exact frequencies or categories.
AB  - PURPOSE: The study was designed to assess if category-based Food Frequency
      Questionnaires (FFQ) could be substituted for exact-frequency based
      questionnaires. METHODS: Nutrient estimates on 203 subjects from Toronto, Canada,
      derived from recoding an exact frequency based 132 item food frequency
      questionnaire (E-FFQ) into categories were evaluated for validity against a 7-day
      food record (FR). RESULTS: Among men, the median Pearson's correlation
      coefficient (for energy adjusted nutrients) between FR and E-FFQ was 0.53,
      ranging from 0.26 for thiamin to 0.72 for calcium. The median correlation dropped
      to a value of 0.40 (range: 0.18 for thiamin to 0. 56 for carbohydrate) when a
      category-based FFQ (C-FFQ) and FR were compared. Data on women showed a similar
      pattern; a median correlation of 0.50 from E-FFQ and 0.42 from C-FFQ.
      CONCLUSIONS: While the results varied with individual nutrients, overall it is
      concluded that when validated against food records, the use of exact frequencies
      in FFQs yielded higher correlation coefficients for most nutrients, and slightly
      better agreement within quartiles of categories than recoded frequency
      categories.

PMID- 10964002
TI  - Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa
      men.
AB  - PURPOSE: Several lines of evidence suggest that prostate cancer has a hormonal
      etiology. We evaluated factors known to modulate the endocrine system, including
      alcohol and tobacco use, physical activity, and obesity as risk factors for
      prostate cancer. METHODS: Cancer-free controls who participated in a population
      based case-control study from 1986-1989 (81% response rate) were followed through
      1995 for cancer incidence by linkage to the Iowa Cancer Registry; 101 incident
      prostate cancers were identified. RESULTS: Compared with non-users of alcohol,
      men who consumed <22 grams alcohol per week (relative risk [RR] = 1.1; 95%
      Confidence Interval [CI] 0.6-2.1), 22-96 grams alcohol per week (RR = 2.6; 95% CI
      1.4-4. 6) and >96 grams alcohol per week (RR = 3.1; 95% CI 1.5-6.3) were at
      increased risk of prostate cancer after adjustment for age, family history of
      prostate cancer, body mass index, total energy, and intake of carbohydrate,
      linoleic acid, lycopene, retinol, and red meat (p for trend < 0.0001). The
      respective RRs were similar when assessing type of alcohol consumed (beer, wine
      or liquor) or when well-differentiated, localized tumors were excluded. Body mass
      index was only weakly and positively associated with prostate cancer after
      adjustment for age, but this association strengthened after multivariate
      adjustment and exclusion of well-differentiated, localized tumors. For the latter
      tumors, men with a BMI of 24.1-26.6 kg/m(2) and >26.6 kg/m(2) were at elevated
      risk compared to men with a BMI <24.1 kg/m(2). Tobacco use (cigarettes,
      cigar/pipe, chewing tobacco and snuff use), height, weight, and both leisure and
      occupational physical activity were not associated with risk of prostate cancer
      in this cohort. CONCLUSIONS: These data suggest that in white men obesity is a
      risk factor for more clinically significant prostate cancer and confirm limited
      previous reports showing that alcohol consumption is positively associated with
      prostate cancer and that this risk is not limited to any specific type of
      alcohol.

PMID- 10964003
TI  - Metropolitan and non-metropolitan trends in coronary heart disease mortality
      within Appalachia, 1980-1997.
AB  - OBJECTIVES: In this article, we report on metropolitan and non-metropolitan
      trends in coronary heart disease (CHD) mortality within the Appalachian Region
      for the period 1980 to 1997. We hypothesized that trends in CHD mortality would
      be less favorable in non-metropolitan populations with diminished access to
      social, economic, and medical care resources at the community level. METHODS: Our
      study population consisted of adults aged 35 years and older who resided within
      the 399 counties of the Appalachian Region between 1980 and 1997. We examined
      mortality trends for sixteen geo-demographic groups, defined by gender, age,
      race, and metropolitan status of county of residence. For each geo-demographic
      group, we calculated annual age-adjusted CHD mortality rates. Line graphs of
      these temporal trends were created, and log-linear regression models provided
      estimates of the average annual percent change in CHD mortality from 1980 to
      1997. Data on social, economic, and medical care resources for metropolitan vs.
      non-metropolitan counties were also analyzed. RESULTS: Rates of CHD mortality
      were consistently higher in non-metropolitan areas compared with metropolitan
      areas for blacks of all ages and for younger whites. CHD mortality declined among
      almost all geo-demographic groups, but rates of decline were slower among non
      metropolitan vs. metropolitan residents, blacks vs. whites, women vs. men, and
      older vs. younger adults. Non-metropolitan areas had fewer socioeconomic and
      medical care resources than metropolitan areas in 1990. CONCLUSIONS: Appalachia,
      particularly non-metropolitan Appalachia, needs policies and programs that will
      enhance both primary and secondary prevention of CHD, and help diminish racial
      inequalities in CHD mortality trends.

PMID- 10964004
TI  - Stroke risk from multiple risk factors combined with hypertension: a primary care
      based case-control study in a defined population of northwest England.
AB  - PURPOSE: To examine how hypertension interacts with other known risk factors in
      affecting the risk of stroke in a primary care based setting. METHODS: Cases were
      patients with first-ever stroke identified from the community-based stroke
      register in 1994-95 in northwest England. Two controls per case were randomly
      selected from the same primary care site and matched by age and sex. Information
      on predefined risk factors was extracted from medical records. RESULTS: 267 cases
      and 534 controls were included. Adjusted odds ratio (OR) for stroke from
      hypertension was 2.6 (95% confidence interval: 1.7-3.9). In hypertensives who
      were current smokers, risk of stroke was increased 6 fold as compared to non
      smokers without hypertension. Hypertensives who had a preexisting history of
      myocardial infarction or obesity or diabetes had 3 fold higher risks of stroke.
      Subjects with hypertension and with a history of transient ischemic attack or
      atrial fibrillation had > or = 8 fold excess risk of stroke. Among them, the risk
      was greater in those with poorly controlled or untreated hypertension and in
      those with well or moderately controlled as compared to subjects without both
      risk factors. There appeared to be a steady increase in risk of stroke according
      to the number of risk factors present, particularly in hypertensive subjects.
      CONCLUSIONS: Stroke risks in hypertensives associated with combinations of other
      risk factors appeared to follow an additive model. Subjects with multiple risk
      factors should be targeted in order to reduce the overall risk for stroke.

PMID- 10964005
TI  - NHLBI family blood pressure program: methodology and recruitment in the HyperGEN
      network. Hypertension genetic epidemiology network.
AB  - PURPOSE: Hypertension is a common precursor of serious disorders including
      stroke, myocardial infarction, congestive heart failure, and renal failure in
      whites and to a greater extent in African Americans. Large genetic
      epidemiological studies of hypertension are needed to gain information that will
      improve future methods for diagnosis, treatment, and prevention of hypertension,
      a major contributor to cardiovascular morbidity and mortality. METHODS: We report
      successful implementation of a new structure of research collaboration involving
      four NHLBI "Networks," coordinated under the Family Blood Pressure Program. The
      Hypertension Genetic Epidemiology Network (HyperGEN) involves scientists from six
      universities and the NHLBI who seek to identify and characterize genes promoting
      hypertension. Blood samples and clinical data were projected to be collected from
      a sample of 2244 hypertensive siblings diagnosed before age 60 from 960 sibships
      (half African-American) with two or more affected persons. Nonparametric sibship
      linkage analysis of over one million genotype determinations (20 candidate loci
      and 387 anonymous marker loci) was projected to have sufficient power for
      detecting genetic loci promoting hypertension. For loci showing evidence for
      linkage in this study and for loci reported linked or associated with
      hypertension by other groups, genotypes are compared in hypertensive cases versus
      population-based controls to identify or confirm genetic variants associated with
      hypertension. For some of these genetic variants associated with hypertension,
      detailed physiological and biochemical characterization of untreated adult
      offspring carriers versus non-carriers may help elucidate the pathophysiological
      mechanisms that promote hypertension. RESULTS: The projected sample size of 2244
      hypertensive participants was surpassed, as 2407 hypertensive individuals (1262
      African-Americans and 1145 whites) from 917 sibships were examined. Detailed
      consent forms were designed to offer participants several options for DNA
      testing; 94% of participants gave permission for DNA testing now or in the future
      for any confidential medical research, with only 6% requesting restrictions for
      tests performed on their DNA. Since this is a family study, participants also are
      asked to list all first degree relatives (along with names, addresses, and phone
      numbers) and to indicate for each relative whether they were willing to allow
      study staff to make a contact. Seventy percent gave permission to contact some
      relatives; about 30% gave permission to contact all first degree relatives; and
      less than 1% asked that no relatives be contacted. Successes after the first four
      years of this study include: 1) productive collaboration of eight centers from
      six different locations; 2) early achievement of recruitment goals for study
      participants including African-Americans; 3) an encouraging rate of consent for
      DNA testing (including future testing) and relative contacting; 4) completed
      analyses of genetic linkage and association for several candidate gene markers
      and polymorphisms; 5) completed genotyping of random markers for over half of the
      full sample; and 6) early sharing of results among the four Family Blood Pressure
      Program networks for candidate and genome search analyses. CONCLUSIONS:
      Experience after four years of this five-year program (1995-2000) suggests that
      the newly initiated NHLBI Network Program mechanism is fulfilling many of the
      expectations for which it was designed. It may serve as a paradigm for future
      genetic research that can benefit from large sample sizes, frequent sharing of
      ideas among laboratories, and prompt independent confirmation of early findings,
      which are required in the search for common genes with relatively small effects
      such as those that predispose to human hypertension.

PMID- 10964006
TI  - Relation between green tea consumption and the severity of coronary
      atherosclerosis among Japanese men and women.
AB  - PURPOSE: To examine the relation between green tea consumption and
      arteriographically determined coronary atherosclerosis. METHODS: Study subjects
      were 512 patients (302 men and 210 women) aged 30 years or older who underwent
      coronary arteriography for the first time at four hospitals in Fukuoka City or
      one hospital in an adjacent city between September 1996 and August 1997.
      Lifestyle characteristics including green tea consumption were ascertained before
      arteriography by a questionnaire supported with interview. RESULTS: 117 men
      (38.7%) and 50 women (23.8%) had significant stenosis of one or more coronary
      arteries. Green tea consumption tended to be inversely associated with coronary
      atherosclerosis in men, but not in women. An evident, protective association
      between green tea and coronary atherosclerosis was observed in a subgroup of 262
      men excluding those under dietary or drug treatment for diabetes mellitus. In
      this subgroup, after adjustment for traditional coronary risk factors and coffee,
      odds ratios of significant stenosis for consumption of 2-3 cups and 4 or more
      cups per day were 0.5 (95% confidence interval 0.2-1.2) and 0.4 (0.2-0.9),
      respectively, as compared with a consumption of one cup per day or less.
      CONCLUSIONS: The results indicate that green tea may be protective against
      coronary atherosclerosis at least in men.

PMID- 10964007
TI  - Formation of N-alkylprotoporphyrin IX after interaction of porphyrinogenic
      xenobiotics with rat liver microsomes.
AB  - Mechanism-based inactivation of selected cytochrome P450 (CYP) isozymes by
      xenobiotics can lead to N-alkylation of the heme moiety and the formation of
      ferrochelatase-inhibitory N-alkylprotoporphyrin IX (N-alkylPP), resulting in
      hepatic porphyrin accumulation and porphyria. Therefore, it is important to
      determine which of the CYP isozymes are responsible for N-alkylPP formation. Our
      objective was to determine if N-alkylPPs could be isolated from rat liver
      microsomes following interaction in vitro with porphyrinogenic xenobiotics, and
      if so, whether they are produced in amounts sufficient for further studies using
      microsomes containing cDNA-expressed human hepatic CYP isozymes. The in vitro
      formation of N-alkylPP was observed following incubation of 3
      [(arylthio)ethyl]sydnone; allylisopropylacetamide; and 3, 5-diethoxycarbonyl-1,4
      dihydro-2,6-dimethyl-4-ethylpyridine; but not 1-aminobenzotriazole, with rat
      hepatic microsomes. However the overall N-alkylPP yield per nmol CYP in vitro was
      much lower than previously observed in vivo. It was concluded that microsomal
      preparations containing cDNA-expressed CYP isozymes do not contain sufficient CYP
      for in vitro studies designed to isolate N-alkylPP and human liver microsomes
      would be a more appropriate source of N-alkylPP because they contain higher
      levels of total CYP.

PMID- 10964008
TI  - A method of reducing the opioid withdrawal intensity using progressively
      increasing doses of naloxone.
AB  - We assessed the withdrawal intensity in acutely morphine-dependent mice using a
      pretreatment with escalating doses of naloxone. All animals received a single
      dose of morphine (100 mg/kg) for the induction of acute opioid dependency. Group
      1 (control) received three injections of normal saline and then naloxone 0.8
      mg/kg. Group 2 received increasing pretreatment doses of naloxone (0.1, 0.2, and
      0.4 mg/kg) and a challenge dose of 0.8 mg/kg. Group 3 received three injections
      of naloxone 0.1 mg/kg and a challenge dose of 0.8 mg/kg. Groups 4 and 5 were used
      to verify whether ED(50) found in previous studies was comparable with values
      obtained in the current experiments. The withdrawal intensity was determined by
      the number of jumps. The mice of group 1 exhibited significantly more jumps after
      0.8 mg/kg of naloxone as compared with group 2. The number of jumps in response
      to naloxone between groups 1 and 2 and groups 2 and 3 was not significantly
      different. The results show that pretreatment with increasing naloxone doses
      significantly reduced the withdrawal intensity as compared with the control
      group; whereas pretreatment with repeated low antagonist did not reduce it
      significantly.

PMID- 10964009
TI  - High-affinity [3H] kainic acid binding to brain membranes: a re-evaluation of
      ligand potency and selectivity.
AB  - [3H]Kainic acid ([3H]KA) is a widely used tool for studying the KA class of
      excitatory amino acid receptors. [3H]KA of significantly higher specific activity
      has become available permitting use of radioligand concentrations below the
      dissociation constant (K(D)) of the high-affinity binding site. We employed low
      radioligand (0.05-0.2 nM) and receptor concentrations (0.01 nM) to gain new
      insights into the binding characteristics of the high-affinity KA binding site in
      a standard preparation of lyzed synaptosomal membranes from the cerebral cortex
      of male Sprague-Dawley rats. Under these conditions, KA binds to a single class
      of high-affinity sites with a K(D) of 1.0+/- 0.3 nM. The potencies of competing
      agents are considerably higher than published reports. Specifically, domoic acid,
      glutamate, and glutamine exhibit IC(50) values for displacing [3H]KA of 0.37+/
      0.02, 94+/-13, and 1500+/-500 nM, respectively. Domoate (1 microM) was tested
      against a panel of 32 central nervous system binding sites and found to be
      inactive at each, indicating this toxin displays considerable selectivity. This
      study illustrates the remarkable potency of domoic acid and underlines the
      importance of performing radioligand binding studies at concentrations of
      constituents that permit characterization of high-affinity interactions.

PMID- 10964010
TI  - Method for comparison of the hemodynamic effects of equi-antinociceptive oral
      doses of drugs in anesthetized rats.
AB  - In a typical flowchart for discovery of novel analgesic (or other) agents, a
      critical path often involves maximization of the separation of the therapeutic
      endpoint from known adverse-effect (AE) endpoint(s). Although strategies can
      easily be designed for in vitro paradigms such as high-throughput screening,
      extension to in vivo testing can represent a major obstacle to the rapid
      progression to the next step in development. The problem can be particularly
      acute when the assessment is required for oral dosing, and when it is not known
      if the therapeutic and AE mechanism(s) of action are the same. As a case in
      point, alpha(2)-adrenoceptor (alpha(2)-AR) agonists have potential therapeutic
      use as analgesics, but they also produce cardiovascular (CV) effects. However,
      whether the two effects are inexorably linked has not been resolved, particularly
      for oral administration. The present study used a novel method for comparing the
      CV effects produced by alpha(2)-AR agonists given by intraduodenal administration
      to anesthetized rats at fixed ratios of the oral antinociceptive ED(50) dose of
      each agonist. The technique provided a useful screen of compounds. In
      addition,there was no correlation between CV endpoints and alpha(2A)-AR affinity,
      suggesting that oral alpha(2)-AR-mediated analgesia and CV effects might be
      separable or that other mechanisms might be involved.

PMID- 10964011
TI  - The chronic infusion of hexamethonium and phenylephrine to effectively clamp
      sympathetic vasomotor tone. A novel approach.
AB  - There are several ways to assess the sympathetic nervous system (i.e. , nerve
      recording, sympathectomy, etc.), each of which has its own limitations. The
      present study was conducted to establish a standard, testable chronic ganglionic
      blockade protocol with a fixed level of adrenergic vasomotor tone. Rats were
      instrumented with radio telemetry pressure transducers and venous catheters for
      continuous measurement of arterial pressure and infusion of pharmacologic agents,
      respectively. After 3 days of control measurements, rats were infused for 9 days
      with a continuous dose of the ganglionic blocking agent, hexamethonium and the
      alpha-adrenergic agonist, phenylephrine. In this way, sympathetic tone was
      effectively "clamped," which maintained a normal level of arterial pressure.
      Control pressure between hexamethonium + phenylephrine (HEX + PE) treated rats
      (101+/-2 mm Hg) and saline (VEHICLE) treated rats (101+/-2 mmHg) was not
      different. By day 9 of the infusion, there was no difference in arterial pressure
      between groups (VEHICLE: 101+/-3 mm Hg, HEX + PE: 103+/-3 mm Hg) or from the
      control period, although heart rate was significantly less in HEX + PE rats
      (VEHICLE: 406+/-9 beats/min vs. HEX + PE: 343+/-6 beats/min). The effectiveness
      of this technique was validated by measuring cardiac baroreceptor reflex
      sensitivity, as well as the pressor response to the direct ganglionic stimulating
      agent, 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP). Compared to VEHICLE
      rats, HEX + PE rats showed no tachycardic response to depressor stimuli and an
      absence of a pressor response to DMPP. We conclude that this protocol is a useful
      technique to chronically, yet reversibly, block the sympathetic nervous system in
      experimental settings.

PMID- 10964012
TI  - Norepinephrine measurement in the isolated, blood-perfused papillary muscle of
      the dog by using ex vivo microdialysis.
AB  - Subendocardial interstitial norepinephrine (NE) was measured in the isolated,
      blood-perfused papillary muscle (PM) preparation of the dog by using ex vivo
      microdialysis. A microdialysis fiber was inserted into the base of the PM and
      perfused with Ringer's solution at a rate of 1 microl/min. Dialyzed NE
      concentrations were measured by high-performance liquid chromatography with an
      electrical detector. The basal dialyzed NE concentration from the subendocardial
      interstitium was 1.74+/-0.24 nM (n = 12, mean +/- SE). When the anterior septal
      artery was occluded for 5 min, the dialyzed NE concentration from the
      subendocardial interstitium 0-5 min after occlusion increased to 2.90 +/-0.61 nM
      (n = 12, p<0.05 versus before occlusion). When desmethylimipramine, a neuronal
      uptake 1 inhibitor, was administered into the anterior septal artery at a rate of
      100 nmol/ml for 30 min, dialyzed NE concentration substantially increased from
      1.55+/-0.33 to 2.63+/-0.34 nM (n = 3, p<0.05). Likewise, the occlusion-induced
      increase in dialyzed NE was augmented to 3.75+/-0.90 nM by desmethylimipramine
      infusion into the anterior septal artery. These observations suggested that the
      ex vivo microdialysis of the isolated, blood-perfused PM preparation of the dog
      is a sensitive method for measuring the subendocardial interstitial NE and that
      coronary artery occlusion increases the subendocardial interstitial NE as early
      as within 5 min.

PMID- 10964013
TI  - Statistical methods for analyzing repeated measures.
AB  - Repeated measurements arise frequently in biomedical research. In many
      situations, the scientific question of interest concerns finding differences in
      the measurements between groups. This question is frequently addressed by using
      analysis of variance-type methods that fail to incorporate information regarding
      the repeated sampling design of the experiment. In this paper, we provide an
      introduction to nonstatisticians of two approaches for analyzing such data. The
      procedures can be performed by using available software. These methods are
      illustrated on data from a preclinical study conducted by ZymoGenetics.

PMID- 10964014
TI  - Pharmacological validation of an automated method of pain scoring in the formalin
      test in rats.
AB  - In 1997, we described a new automated method of scoring the pain behaviors in the
      formalin test. The algic behavior was automatically measured with the help of a
      video-analysis system. The time during which the animal grooms, licks, or bites
      itself was used as the parameter of pain. In the present study, we tested various
      analgesics to realize a pharmacological validation of the system. The effect of
      opiate analgesic (morphine, i.v.), nonsteroidal anti-inflammatory drugs
      (paracetamol, i.v., piroxicam, i.v., indomethacin, i.v.), antidepressant drugs
      (clomipramine, desipramine, nortryptyline, and paroxetine, i.p.), and serotonin
      (i.t.) were analyzed. A dose of 1.25 mg/kg of morphine induced a decrease in the
      scores of phases 1 and 2. Naloxone (0.25 mg/kg) reversed the effect of morphine
      (2.5 mg/kg). A 20-mg/kg dose of indomethacin induced a decrease in the second
      phase, and paracetamol induced a decrease in both phases (analgesic doses were
      400 mg/kg and 200 mg/kg for first and second phases, respectively). Piroxicam had
      no effect on the pain scores. Clomipramine, desipramine, and paroxetine at a dose
      of 5 mg/kg induced a significant decrease in the second phase. Nortriptyline had
      no effect on the pain scores. A dose of 75 microg of serotonin induced a decrease
      in both phases 1 and 2. This study demonstrated that this system shows a good
      pharmacological sensitivity, although it is lower than that of manual assessment.

PMID- 10964015
TI  - Effect of heat shock on the vascular contractility in isolated rat aorta.
AB  - Stresses such as heat shock, ischemia, and irradiation have been known to induce
      heat shock proteins in various tissues. We investigated the effects of heat shock
      on the vascular contractility by using isolated rat aorta. Rat thoracic aortic
      rings were mounted in an organ bath maintained at 37 degrees C. For heat shock,
      aortic ring preparations were exposed to 42 degrees C for either 15 or 45 min
      (heat shock group), whereas the control group was left at 37 degrees C. Eight
      hours after heat shock, aortic ring preparations were subjected to contractions
      with high K(+) membrane-depolarizing solution. After functional study, tissues
      were frozen for measurement of heat shock protein 70 (HSP70). Heat shock not only
      increased the expression of HSP70 in the rat aorta, but also augmented
      contractions to KCl whether endothelium was present or denuded. Short exposure of
      tissues to 42 degrees C for 15 min did not work either. These results suggest
      that heat shock increases vascular contractility in isolated aortic strips.

PMID- 10964017
TI  - President's page

PMID- 10964016
TI  - Laird wilson, jr, PhD. (1943-2000)

PMID- 10964018
TI  - Presidential address

PMID- 10964020
TI  - Effect of repetitive umbilical cord occlusions on neuronal brain activity
      measured by the cerebral function analyzing monitor and histologic outcome in
      immature fetal sheep.
AB  - OBJECTIVE: To examine the effect of repetitive total umbilical cord occlusions on
      electrocortical brain activity as measured by cerebral function analyzing
      monitoring (CAFM) and the histologic outcome in immature sheep fetuses. STUDY
      DESIGN: We performed brief repeated total umbilical cord occlusions, two every 5
      minutes, in 12 immature sheep fetuses (at 90 days of gestation, term 147 days)
      until fetal mean arterial pressure dropped below 50% of baseline value during two
      successive occlusions. A pair of electrodes was inserted on the parietal dura for
      recording of electrocortical brain activity (ECoG). Off-line ECoG signal
      processing consisted of amplitude integrated analysis (CFAM) and spectral
      analysis. Fetal blood gas analyses were performed at regular intervals just
      before subsequent umbilical cord occlusions. Three days after the occlusion
      neuronal damage was evaluated histologically in three regions of the fetal brain.
      RESULTS: CFAM amplitide parameters decreased significantly during the first
      occlusion and remained so during the entire repetitive occlusion period (analysis
      of variance [ANOVA]; P <.05). Spectral analysis of the ECoG signal demonstrated
      no changes in the distribution of frequency bands. Progressive acidemia and
      hypotension developed with ongoing occlusions. Five fetuses died at the end or
      shortly after the entire repetitive occlusion period. No neuronal damage or
      macroscopic intraventricular and/or germinal matrix hemorrhage was observed in
      the surviving fetuses. CONCLUSION: Repetitive umbilical cord occlusions in
      immature sheep fetuses resulted in functional, not structural changes of the
      fetal brain in surviving fetuses. At this gestational age, amplitude analysis is
      more sensitive than spectral analysis of the ECoG signal to functional changes of
      the compromised fetal brain.

PMID- 10964019
TI  - Effects of long-term high-altitude hypoxia on isolated fetal ovine coronary
      arteries.
AB  - OBJECTIVE: To examine the effects of long-term high-altitude hypoxia on the
      contractile properties of isolated fetal coronary arteries. METHODS: Maximal
      contractile responses (T(max)) to 90 mmol/L KCl and the thromboxane A(2) mimetic
      U46619 were measured in proximal (PLCx) and distal left circumflex (DLCx), left
      anterior descending (LAD), and right coronary arterial (RCA) rings from high
      altitude and control fetuses. Paired studies were conducted with and without
      nitric oxide synthase (NOS) inhibitors, Nomega-nitro-L-arginine and Nomega-nitro
      L-arginine ester. RESULTS: In high-altitude fetuses, 90 mmol/L KCl T(max)
      responses in both intact and NOS-blocked rings decreased by approximately 62% in
      PLCx, approximately 59% in DLCx, approximately 57% in LAD, and approximately 47%
      in RCA (n = 9-18/group; P <.05). High-altitude vessels also exhibited decreased
      sensitivity to U46619. NOS blockade potentiated T(max) to U46619 in the high
      altitude RCA segments and augmented T(max) to U46619 in high-altitude RCA
      compared with its treated control counterpart (P <. 05). CONCLUSION: These
      results suggest that nitric oxide influences the pharmacologic responsiveness of
      the RCA to U46619. Furthermore, long-term high-altitude hypoxia significantly
      alters the contractile capabilities of fetal coronary arteries. These
      observations may partially explain the maintained redistribution of cardiac
      output to the fetal heart during exposure to long-term high-altitude hypoxia.

PMID- 10964021
TI  - Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical
      cord occlusion in the preterm ovine fetus.
AB  - OBJECTIVE: To determine whether repeated hypoxic insults with umbilical cord
      occlusion over 4 days will lead to activation of the hypothalamic-pituitary
      adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine
      fetus. METHODS: Umbilical cord occlusions of 90 seconds duration were performed
      every 30 minutes for 3 to 5 hours each day (experimental group n = 7, control
      group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was
      sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol.
      Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also
      were localized and quantified by in situ hybridization. RESULTS: During umbilical
      cord occlusions fetal arterial oxygen pressure (approximately 17 mmHg) and pH
      (approximately 0.05) decreased, and carbon dioxide pressure increased
      (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood
      gas or pH change over successive occlusions for any of the 4 study days. Plasma
      ACTH increased, as measured after cord occlusion and over the course of
      successive cord occlusions on days 1 and 4, and returned to control values by the
      next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15
      +/- 3 compared with 101 +/- 25 pg/mL, P <.05). Plasma cortisol increased, as
      measured after cord occlusion and over the course of successive cord occlusions
      on day 4 only (2.7 +/- 0.4 to 4. 7 +/- 0.3 ng/mL, P <.05). POMC mRNA increased
      2.5-fold in the pars distalis of the pituitaries from cord occlusion compared to
      control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was
      detected in the pars distalis only, was unaltered. CONCLUSION: Repetitive
      umbilical cord occlusion in the preterm ovine fetus resulted in the activation of
      the HPA axis, with increased adrenocortical responsiveness over time, and
      involved differential regulation of POMC mRNA expression in the pars distalis and
      pars intermedia of the pituitary, but with no change in GR.

PMID- 10964022
TI  - Maternal intravenous administration of long chain n-3 polyunsaturates to the
      pregnant ewe in late gestation results in specific inhibition of prostaglandin h
      synthase (PGHS) 2, but not PGHS1 and oxytocin receptor mRNA in myometrium during
      betamethasone-induced labor.
AB  - OBJECTIVES: Both the onset of labor and time to delivery during betamethasone
      induced delivery are delayed by omega-3 polyunsaturated fatty acid (PUFA)
      administration to pregnant sheep. That fatty acid also inhibits the labor-related
      increase in maternal plasma estradiol and maternal and fetal prostaglandin E(2).
      To evaluate the mechanism of inhibition of prostaglandin production and delay of
      onset of labor and time of delivery in PUFA-treated sheep, we determined the
      effect of PUFA on myometrial prostaglandin H synthase (PGHS) 1 and 2 and oxytocin
      receptor mRNA levels in betamethasone-induced labor. METHODS: At 124 days'
      gestation, a 20% emulsion of either intralipid (IL, n = 6) or PUFA (n = 6) was
      infused continuously (3 mL/kg per day) intravenously (IV) to the ewe. At 125
      days' gestation, betamethasone was administered IV (10 microg/h over 48 hours) to
      fetuses of both intralipid- and PUFA-treated ewes. Myometrium was collected at
      necropsy either during betamethasone-induced labor as evaluated by myometrial
      electromyography or within 5 days of the termination of betamethasone infusion,
      if delivery did not occur after fetal betamethasone infusion. Total myometrial
      RNA was analyzed by Northern blot for oxytocin receptor and PGHS1 and 2 mRNA
      normalized for 18s. RESULTS: Treatment with PUFA decreased myometrial PGHS2 mRNA
      but did not alter myometrial PGHS1 and oxytocin receptor mRNA after betamethasone
      administration. CONCLUSIONS: This finding provides a mechanism whereby PUFA
      delays betamethasone-induced delivery in sheep and suggests a potential role of
      PUFA as an effective tocolytic agent in human pregnancy.

PMID- 10964023
TI  - Association of the missense Glu298Asp variant of the endothelial nitric oxide
      synthase gene with severe preeclampsia.
AB  - OBJECTIVES: A large number of studies suggest that abnormalities in nitric oxide
      (NO) synthesis may contribute to the development of preeclampsia. We recently
      identified a variant within exon 7 of the endothelial NO synthase (eNOS) gene: G
      to T conversion at nucleotide position 894 resulting in replacement of glutamic
      acid with aspartic acid at codon 298 (Glu298Asp). We analyzed the association
      between the Glu298Asp eNOS gene variant and preeclampsia. STUDY DESIGN: The study
      included 152 preeclampsia patients (35 mild, 80 severe, and 37 superimposed) and
      170 control subjects. Screening for the Glu298Asp eNOS gene variant was carried
      out by analysis of polymerase chain reaction-restriction fragment length
      polymorphism. RESULTS: The frequency of the Glu298Asp variant was significantly
      higher in the severe preeclampsia group (28.8%) than in the control (14.1%; p <.
      01), superimposed preeclampsia (8.1%; p <.01), and mild preeclampsia (11.4%; p
      <.01) groups. CONCLUSIONS: We conclude that the presence of the Glu298Asp eNOS
      gene could be a marker of increased risk of developing severe preeclampsia.

PMID- 10964024
TI  - Differential regulation of stromelysin-1 (matrix metalloproteinase-3) and
      matrilysin (matrix metalloproteinase-7) in baboon endometrium.
AB  - OBJECTIVE: To investigate in vivo expression of matrix metalloproteinase enzymes
      (MMP), MMP-3 and MMP-7, by the baboon endometrium in relation to the process of
      tissue remodeling that accompanies menstruation in the primate. METHODS:
      Endometrial tissues and uterine fluids obtained from reproductively intact
      cycling baboons, cycling baboons treated with an anti-progestin, and
      ovariectomized steroid-treated baboons were evaluated for MMP mRNA expression and
      protein production by using multiple analytic techniques. RESULTS: The pattern of
      MMP protein production matched the pattern of MMP mRNA expression. In intact
      cycling baboons, MMP mRNA expression and protein production were specific to cell
      type and stage of the menstrual cycle. Endometrial stroma expressed minimal
      amounts of MMP-3 during the proliferative and secretory stages, whereas
      endometrial epithelia expressed MMP-7 during the proliferative stage. Expression
      of stromal MMP-3 and epithelial MMP-7 increased during early menses.
      Administration of anti-progestin beginning on the day of the LH surge increased
      MMP-7 but not MMP-3 expression at the mid secretory phase. Expression of MMP-3
      and MMP-7 in the ovariectomized steroid-treated animals paralleled that of the
      intact cycling animals. CONCLUSIONS: These results highlight the similarity of
      human and baboon endometrial MMP-3 and MMP-7 production, providing further
      evidence for use of the baboon as a model for studying events associated with
      hormonally regulated changes during the menstrual cycle. These results also
      demonstrate that endometrial epithelial MMP-7 is suppressed by progesterone in
      the baboon endometrium, but endometrial stromal MMP-3 is regulated by a different
      mechanism.

PMID- 10964025
TI  - Preclinical evidence for therapeutic efficacy of selective estrogen receptor
      modulators for uterine leiomyoma.
AB  - OBJECTIVE: Uterine leiomyoma are the most common gynecologic neoplasm and a
      primary cause of hysterectomy in premenopausal women. Preclinical studies were
      conducted in the Eker rat model to investigate the potential efficacy of
      selective estrogen receptor modulators (SERMs) as therapeutic agents for this
      tumor. METHODS: Twelve-month-old Eker rats were randomized into five treatment
      arms including tamoxifen, placebo, LY 326315, vehicle, and no treatment.
      Additional animals received ovariectomy or sham surgery at 4 months of age to
      determine the effect of ovarian ablation on tumor development. The study was
      terminated after 2 to 4 months of treatment, and tumor incidence, size,
      proliferative and apoptotic indices were determined. Size and incidence data were
      subjected to chi-square analysis. One-way analysis of variance and Fisher's least
      significant difference tests were used to compare proliferative and apoptotic
      indices. RESULTS: Ovariectomy virtually ablated leiomyoma development, indicating
      that these tumors were dependent on ovarian hormones for growth and development.
      Treatment with tamoxifen or raloxifene analog LY 326315 reduced leiomyoma
      incidence by 40-60% and reduced the size of remaining tumors. The effect of SERMs
      on leiomyomas was mediated by a decrease in cell proliferation without a decrease
      in apoptotic index. CONCLUSION: SERMs have been shown to be therapeutically
      efficacious against breast cancer and to reduce tumor incidence in women at
      increased risk for this disease. The present data indicate that therapeutic
      efficacy may also be extended to uterine leiomyoma and demonstrate the utility of
      this animal model for preclinical studies to identify new therapeutic modalities.

PMID- 10964026
TI  - Effects of an oral contraceptive combination with or without androgen on mammary
      tissues: a study in rats.
AB  - OBJECTIVES: Oral contraceptive (OC) therapy has long been known to produce
      hypoandrogenemia. However, androgens are not part of any OC therapy available to
      women. This project was designed to evaluate the effects of low-estradiol
      containing OC, with or without methyltestosterone (MT), on cell proliferation and
      progesterone receptor (PgR) expression in mammary gland epithelia of virgin
      female rats. METHODS: Sixty rats were divided into four groups. One group
      received OCs, whereas a second group received OC plus MT. A third group of rats
      was treated with an antiandrogen to mimic the hypoandrogenemic effects caused by
      OC therapy. All treated groups were compared with age-matched untreated controls.
      RESULTS: After 15 weeks of treatment, no inflammatory, precancerous, or cancerous
      lesions were observed in any treatment group. OC plus MT therapy caused
      significant suppression of epithelial proliferation, a reduction in the number of
      proliferating cell nuclear antigen-labeled cells, and an increase in the number
      of PgR-labeled cells. CONCLUSIONS: Our results suggest that a medication
      containing an estrogen-progestin-androgen combination has antiproliferative
      effects in mammary glands of experimental animals that could prove to have breast
      protective potential in women.

PMID- 10964027
TI  - The molecular basis of renal tubular transport disorders.
AB  - Sodium and water homeostasis are key to the survival of organisms. Reabsorption
      of sodium and water occurs throughout the tubule structure of the nephron, the
      basic functional unit of the kidney, by various transport mechanisms. Altered
      transport protein function can lead to renal tubular disorders resulting in
      metabolic alkalosis, hypokalemia, hypertension, and decreased capacity to
      concentrate urine, for instance. However, recent advances in molecular
      physiology, molecular genetics and expression cloning systems have aided in
      unraveling the molecular basis of some renal tubular disorders. This review will
      examine the molecular basis of Bartter's syndrome, Gitelman's syndrome, Liddle's
      syndrome, and autosomal nephrogenic diabetes insipidus. An understanding of the
      molecular basis of these disorders of the human kidney can give us a better
      understanding of basic renal function of lower mammals and other vertebrates.

PMID- 10964028
TI  - The lysosomes of earthworm chloragocytes: biochemical and morphological
      characterization.
AB  - Nine latent and sedimentable acid hydrolases have been detected in the
      homogenates of earthworm chloragocytes. Their full activity was revealed by
      treatment with Triton X-100, a Waring blender treatment, freezing and thawing,
      hypotonic media or incubation at pH 5 and 25 degrees C. Solubilization paralleled
      the activation of the enzymes. Together with kinetic studies, these results
      indicate that the acid hydrolases of the chloragocytes are inside typical
      lysosome-like particles whose membrane is impermeable to their substrates. It
      could be shown by density equilibration centrifugation that the lysosomes of
      those cells constitute a heterogeneous population of subcellular particles
      distinct from the chloragosomes. Moreover, their digestive function has been
      directly demonstrated by the capture and degradation of serum albumin. The
      lysosomes of the chloragocytes have been clearly identified as polyvesicular
      bodies by electron microscopic analysis of the fractions obtained by density
      equilibration centrifugation and by examination of the whole tissue, as such or
      after endocytosis of serum albumin or ferritin. Finally, our results do not
      support a possible relationship between the lysosomes and the chloragosomes of
      the chloragocytes.

PMID- 10964029
TI  - Bimodal breathing in the estuarine crab Chasmagnathus granulatus Dana 1851-
      physiological and morphological studies.
AB  - Chasmagnathus granulatus is an estuarine crab which actively moves from subtidal
      to supratidal areas. To elucidate the possible existence of extrabranchial sites
      for aerial gas exchange, we measured respiratory and acid-base variables in
      animals with and without branchial water (controls and experimental crabs,
      respectively) during air exposure. An histological study of the branchiostegite
      was also performed. Throughout 4 h of emergence C. granulatus did not suffer
      venous hypoxia, even without branchial water. The rate of oxygen uptake (M(O(2)))
      was similar in both groups. The rate of carbon dioxide excretion (M(CO(2))) and
      the gas exchange ratio (R) significantly decreased during emergence in both
      groups, with R significantly lower for experimental crabs. Consequently, CO(2)
      was accumulated in the hemolymph. This variable stabilized after 90 min in
      control animals, but experimental crabs continued accumulating CO(2).
      Histological study of the branchiostegites demonstrated the presence of an
      attenuated and greatly perfused epithelium facing the branchial chamber lumen,
      with a shortest diffusion distance of 0.5 microm. Simple folds and lobulated
      projections increase the respiratory surface area. These results suggest that C.
      granulatus is a bimodal breathing crab, active both in water and air. When
      emerged, this species extract oxygen directly from air through branchiostegal
      lungs, but relies on branchial exchange to eliminate carbon dioxide.

PMID- 10964030
TI  - Osmoregulation of the Nile crocodile, Crocodylus niloticus, in Lake St. Lucia,
      Kwazulu/Natal, South Africa.
AB  - Nile crocodiles of three age classes, hatched in captivity and reared in fresh
      water, when exposed acutely to water of 17 and 35 ppt NaCl, suffered marked
      dehydration, were lethargic, ceased to feed and lost mass. When exposed to
      gradually increasing salinities (3-35 ppt), with a short acclimation period at
      each salinity, crocodiles survived, continued to feed and increased in mass and
      size. All age classes had a relatively constant plasma osmolality across the
      salinity spectrum. Cloacal urine osmolality varied throughout the acclimation
      experiment, but did not increase with increasing salinity. No significant
      increase was found in plasma concentrations of any of the osmolytes. There was a
      trend of decreasing cloacal urine [Na(+)] and [Cl(-)] and increasing cloacal
      urine [K(+)] with increased salinity, indicating that urine was not an important
      route for Na(+) and Cl(-) excretion. Crocodiles exposed to saline conditions
      maintained relatively constant plasma uric acid concentrations, but urinary uric
      acid concentrations increased markedly with increasing salinities. This suggests
      that uric acid is the main constituent of nitrogenous waste excretion in saline
      exposed Nile crocodiles. As in Crocodylus porosus, C.niloticus has the
      physiological ability to survive and thrive in periodically hyper-osmotic
      environments. However, its euryhalinity is restricted, in that acute exposure to
      sea water leads to dehydration, but with an acclimation period at lower
      salinities, it survives and thrives in sea water.

PMID- 10964031
TI  - Structure and composition of the aragonitic crossed lamellar layers in six
      species of Bivalvia and Gastropoda.
AB  - The microstructures, the chemical composition and the soluble organic matrices of
      the aragonitic crossed lamellar layers of the shells of six species of molluscs
      have been studied. The microstructures and chemical contents are similar, whereas
      the quantities of organic matrices are variable. All the soluble matrices are
      glycoproteins, with low S contents. Their molecular weights, the protein-sugar
      ratios and acidities are variable. Neither a gastropod nor a bivalve pattern is
      recognized. The diversity of the organic matrices probably plays a main role in
      the fossilization processes of mollusc shells.

PMID- 10964032
TI  - Heart rate and rate of oxygen consumption during flight of the barnacle goose,
      Branta leucopsis.
AB  - We report the first measurements of heart rate (f(H)) and the rate of oxygen
      consumption (V(O(2))) during flights from a species of bird larger than 500 g.
      V(O(2))was obtained from nine forward flapping flights of 8.9 min mean duration
      at a mean speed of 13.2 m s(-1) performed by three barnacle geese of mean mass
      1.68 kg. Mean V(O(2))was 332 ml min(-1)or 201 ml min(-1) kg(-1). Sixteen flights
      were obtained from two of these birds equipped with heart rate data loggers, both
      when they were wearing a V(O(2)) mask and when they were not. During flights with
      the mask (mean duration 7.4 min), mean f(H) was 472 beats per min and during
      flights without the mask (mean duration 8.0 min) it was 391 beats per min. Heart
      rate was also measured in another goose flying without a respiratory mask and
      mean f(H) for all the three birds (mean mass 1.7 kg) flying without a mask for an
      average of 7.9 min at 13 m s(-1) was 378 beats per min. Resting f(H) for these
      three birds was 79 beats per min. The values of f(H) during flight are greater
      than those obtained from the same species during their autumn migration from
      Spitsbergen to southern Scotland. The possible reasons for this are discussed.

PMID- 10964033
TI  - Fatty acid, carotenoid and vitamin A composition of tissues of free living gulls.
AB  - The aim of this study was to investigate fatty acid and carotenoid profile as
      well as vitamin A (retinol and retinol esters) content in gull (Larus fucus)
      tissues. Palmitic (16:0) and stearic (18:0) fatty acids were major saturates in
      all the tissues studied. Oleic acid (18:1n-9) was the major monounsaturate in the
      tissue phospholipids varying from 11.9% (liver) up to 18.2% (lung). Arachidonic
      acid (20:4n-6) was the major unsaturate in the phospholipid fraction in all the
      tissues. Liver contained the highest total carotenoid concentration which was 5
      and 7 fold higher compared to kidney and pancreas. In the liver beta-carotene was
      major carotenoid. In contrast, in all other tissues beta-carotene was minor
      fraction with lutein being major carotenoid. Zeaxanthin, canthaxanthin, beta
      cryptoxanthin and echinenone were also identified in the gull tissues. Liver and
      kidney were characterised by the highest vitamin A concentrations (1067.5 and
      867.5 microg/g, respectively). Retinol comprised from 55.3% (pancreas) down to 8%
      (kidney) of the total vitamin A but was not detected in the abdominal fat.
      Retinyl palmitate was the major retinyl ester in the liver, kidney and heart
      (44.2; 38.1 and 46.0% of total retinyl esters). In muscles and abdominal fat
      retinyl stearate was the major retinyl ester fraction. Therefore high proportions
      of beta-carotene were found in gull liver and peripheral tissues were enriched by
      lutein and zeaxanthin compared to the liver, a very high concentration of retinyl
      esters in the kidney was observed and tissue-specificity in retinyl ester
      proportions in peripheral tissues was found.

PMID- 10964034
TI  - Oxygen consumption, blood lactate and inter-individual variation in the gulf
      killifish, Fundulus grandis, during hypoxia and recovery.
AB  - Rates of oxygen consumption (M(O(2))) for Fundulus grandis, the gulf killifish,
      were measured in air-saturated water, at four progressively lower levels of
      oxygen and upon normoxic recovery. The pattern of M(O(2)) versus oxygen partial
      pressure (P(w)O(2)) was that of an oxygen regulator, with a critical oxygen
      pressure (P(c)) of 34 torr (1 torr=133.3 Pa). Below this value, M(O(2)) decreased
      and the concentration of blood lactate increased, indicating anaerobic metabolism
      during hypoxia. Recovery was characterized by elevated M(O(2)) compared to the
      initial normoxic exposure, coupled with the rapid clearance of blood lactate.
      Variation in M(O(2)) among the individual fish was appreciable and, in general,
      it was greater at higher levels of P(w)O(2). This inter-individual variation was
      significantly larger than the variation between replicate measures of M(O(2)) for
      a given individual, i.e. it cannot be attributed solely to random error.
      Furthermore, values for M(O(2)) during normoxia were found to be repeatable when
      the same fish were used in multiple experimental trials. The observation of
      significant, repeatable inter-individual variation in M(O(2)) suggests that such
      variation is a real and potentially important feature of fish metabolism.

PMID- 10964035
TI  - Effect of x-organ sinus gland extract on [(35)S] methionine incorporation to the
      ovary of the red swamp crawfish Procambarus clarkii.
AB  - The presence of gonad-inhibiting hormone in the x-organ sinus gland complex was
      evaluated in female Procambarus clarkii. Elimination of gonad-inhibiting hormone
      by way of eyestalk removal resulted in a large acceleration of ovarian
      development. Daily injection of four sinus gland equivalents reduced ovarian
      growth of eyestalk-ablated females by about 50% on day 6. Use of the radiotracer
      [(35)S] methionine showed that gonad-inhibiting activity reached its peak effect
      between 12 and 24 h following sinus gland injection. Dose-response showed that at
      least two sinus gland equivalents were needed to significantly counter the
      accelerated growth induced by eyestalk ablation. The high dose of extract needed
      to cause significant inhibition was attributed to this delayed response, which
      subsequently may have required a relatively prolonged exposure to the hormone.

PMID- 10964036
TI  - A pharmacokinetic interpretation of increasing concentrations of DEHP in
      haemodialysed patients.
AB  - The degree of exposure to DEHP was assessed in 11 patients with chronic renal
      failure undergoing maintenance haemodialysis. The amount of DEHP leached from the
      dialyser during a 4-h dialysis session was estimated by monitoring the DEHP blood
      concentration using a HPLC method. When a patient undergoes a dialysis treatment,
      the concentration of di-2-ethylhexyl phthalate (DEHP) in venous blood is
      increased when the blood crosses through the dialysis apparatus. This increase
      may be explained either because DEHP is not extracted by the dialyser or because
      DEHP comes from the dialysis bath due to contact of blood against plasticized
      pipes. To explain the increasing concentration of DEHP during treatment of renal
      failure using plasticized tubing, we propose a pharmacokinetic compartmental
      model in order to fit raw data obtained from dialysed patients and to get the
      amount of DEHP which enters the body by AUC calculations. Results obtained after
      HPLC analysis show a high degree of interpatient variability in DEHP retained.
      This amount can reach a toxicity level because of repetitive dialysis treatments
      over prolonged periods of time. In the coming years, it seems necessary to
      reconsider the use of DEHP as a plasticizer in medical devices. Highly
      unacceptable amounts of DEHP leached during the dialysis session could be easily
      avoided by careful selection of haemodialysis tubing.

PMID- 10964037
TI  - Measurement of isometric muscle strength: a reproducibility study of maximal
      voluntary contraction in normal subjects and amyotrophic lateral sclerosis
      patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a degenerative disease of unknown cause,
      resulting in the progressive loss of voluntary motor activity. Traditional
      methods of evaluating patients with ALS (neurologic assessment, manual muscle
      testing and rating scales) involve subjective elements and lack the sensitivity
      needed to detect small but meaningful changes in deterioration and therapeutic
      efficacy. This paper presents a recently developed strength measurement
      instrument, useful for the long-term monitoring of muscle strength deterioration
      in ALS. In addition, a reproducibility study to assess the intra- and
      interobserver reliability of maximal voluntary isometric contraction is reported.
      The strength measurement instrument consists of a strain gauge force transducer,
      a bridge amplifier and a mechanical structure to counteract movements. A personal
      computer acquires the strength signal during each voluntary contraction and
      automatically computes the maximal value. Reproducibility of measurement was
      assessed in 18 normal subjects tested twice, on successive days, with the same
      examiner and under the same conditions. The interexaminer reproducibility of
      measurement was assessed in a group of 13 normal subjects and 10 ALS patients.
      Each subject of the two groups was independently examined by three examiners. The
      two reproducibility studies showed a high intraclass correlation coefficient
      (0.91-0.97) and low SEM and measurement error (3-10%) in all muscle regions
      tested. The Bland and Altman plots confirmed these results.

PMID- 10964038
TI  - Measurements of gap pressure and wall shear stress of a blood pump model.
AB  - The centrifugal blood pump with a magnetically suspended impeller has shown its
      superiority as compared to other artificial hearts. However, there is still
      insufficient understanding of fluid mechanics related issues in the clearance
      gap. The design nature of the pump requires sufficient washout in the clearance
      between the impeller and stationary surfaces. As the gap is only 0.2 mm in width,
      it is very difficult to conduct measurements with present instrumentation. An
      enlarged model with 5:1 ratio of the pump has been designed and constructed
      according to specifications. Dimensionless gap pressure measurements of the model
      are very close to the prototype. The measurements of wall shear stress of the
      fluid flow in the clearance gap between the impeller face and inlet casing of a
      blood pump model were accomplished through hot-wire anemometry and rotating disk
      apparatus. Regions of relatively high and low shear stresses are identified.
      These correspond to spots where the likelihood of hemolysis and thrombus
      formation is high. With the use of dimensional analysis, it is found that the
      highest wall shear stress is equivalent to 146 Pa which is much lower than the
      threshold value of 400 Pa for hemolysis reported in the literature.

PMID- 10964039
TI  - Small bowel motility: relationship between smooth muscle contraction and
      electroenterogram signal.
AB  - A study is made to correlate the electrical and mechanical activity of the smooth
      muscle of the small bowel. Bioelectrical signal recording from the intestinal
      serosa (electroenterogram) comprises a slow wave (SW) and spike burst (SB),
      though only the latter reflects intestinal pressure. The electroenterogram and
      smooth muscle pressure are simultaneously recorded in the canine small bowel.
      Spectral and time series analysis of the electroenterogram are performed to
      establish those electrical parameters that best reflect intestinal pressure. The
      results reveal an underlying correlation between the estimated parameters of
      electrical activity and smooth muscle pressure. In addition, parameters derived
      from the spectral techniques were closely correlated to pressure events in the
      intestine, even more so than the variables directly acquired from the classical
      time domain analyses. Specifically, spectral energy above 2 Hz and mean frequency
      (both calculated from the biosignal periodogram), are parameters that identify
      intestinal pressure. The extrapolation of these spectral parameters to long time
      periods could serve to define a motility index (MI) from electrical gut activity.
      In this context, electroenterogram recording and analysis can contribute to solve
      problems inherent to manometric recording, though the need for surgical
      intervention restricts electrical methods to experimental or surgical studies.

PMID- 10964040
TI  - Evaluation of four blood pump geometries: fluorescent particle flow visualisation
      technique.
AB  - Artificial blood pumps play an increasingly important role in the treatment of
      end-stage cardiac failure. The fluid dynamics of blood flow through such devices
      crucially affects their clinical effectiveness. Specifically, if the flow of
      blood stagnates or slowly re-circulates thrombus formation can occur and the
      avoidance of such flow features is a primary consideration in the design of
      pumps. The present study concerns the development of a fluorescent particle
      visualisation technique and its application to investigate the flow environments
      in four prototype blood pump designs. The procedure involves recording video
      images of eight illuminated cross sections through the pumping chambers as the
      pumps operate in a mock circulatory loop using a test fluid seeded with
      fluorescent particles. The technique enabled a semi-quantitative characterisation
      of the entire flow field, throughout the pumping cycle, to be performed for each
      pump design. Flow features were then related to design properties of the
      individual pumps and recommendations made for design optimisation.

PMID- 10964041
TI  - A treadmill-based system for measuring symmetry of gait.
AB  - It has been recognised for centuries that various conditions will lead to
      asymmetries in gait and several researchers have analysed symmetry of gait.
      However, in general such analyses are based on five steps or fewer. A new system
      has been designed and manufactured that is based on a motorised treadmill with
      forceplates (errors +3. 2% and -4.3%) that quickly gathers information on larger
      numbers of steps. It automatically records the data and then performs a semi
      automatic analysis to calculate various parameters from each of the measured
      steps, including: heel strike, toe off, stance phase, swing phase, peak forces
      and loading and unloading rates. Other parameters can also be easily incorporated
      into the analysis such as double support time. Student's t tests are performed
      comparing the means of these parameters. The ratios of the parameters, left to
      right (or uninvolved to involved limbs), are then quoted as Symmetry Indices. It
      has been found to be quick and easy to use and produces results that are both
      readily understood and clinically relevant.

PMID- 10964042
TI  - Limitations of the computerized laryngeal analyzer (CLA) in the assessment of the
      swallowing mechanism.
AB  - This study was devised to assess the repeatability of measurements obtained from
      the Computerized Laryngeal Analyzer (CLA), a commercial system which monitors
      global laryngeal activity through a piezoelectric transducer positioned at the
      level of the thyroid cartilage. Twenty-two healthy subjects (37+/-7 yr) were
      asked to repeat three consecutive times the deglutition of three types of bolus:
      dry (saliva only), liquid (10 ml water) and solid (1 cm(3) biscuit). The whole
      recording session was repeated 4+/-3 days apart. Two parameters were considered:
      amplitude and duration of the deglutition. Both intra- and inter-sessions
      repeatability were assessed by the standard error of measurement. The amplitude
      measurements were often found to be clipped at 100 mV, making duration the only
      parameter suitable for analysis. The duration was homogenous for the three types
      of bolus and no trend effect was found either intra- or inter-sessions. Inter
      sessions repeatability was significantly lower than the intra-session one
      (P<0.05). As a practical implication, a change in duration >/=1 s (=65% of the
      observed mean value) between two separate measurements is required in order to be
      95% confident that it is not due to chance alone. We conclude that the observed
      limitations in the measurements provided by the CLA system, in conjunction with
      its intrinsic characteristic of providing only an uncalibrated measurement of
      global laryngeal activity, seriously question the possibility of using the CLA
      system either as a diagnostic tool or as a substitute of the gold standard method
      (videofluorography).

PMID- 10964043
TI  - Application of combined genetic algorithms with cascade correlation to diagnosis
      of delayed gastric emptying from electrogastrograms.
AB  - The current standard method (radioscintigraphy) for the diagnosis of delayed
      gastric emptying (GE) of a solid meal involves radiation exposure and
      considerable expense. Based on combining genetic algorithms with the cascade
      correlation learning architecture, a neural network approach is proposed for the
      diagnosis of delayed GE from electrogastrograms (EGGs). EGGs were measured by
      placing surface electrodes on the abdominal skin over the stomach in 152 patients
      with suspected gastric motility disorders for 30 min in the fasting state and for
      2 h after a standard test meal. The GE rate of the stomach was simultaneously
      monitored after the meal using radioscintigraphy. Five spectral parameters of EGG
      data in each patient were used as the inputs to a classifier. The classifier was
      designed by using genetic algorithms in conjunction with the cascade correlation
      learning architecture. The main advantage of this technique over the back
      propagation (BP) for supervised learning is that it can automatically develop the
      architecture of neural networks to give a suitable network size for a specific
      problem. The resulted neural network with three hidden units exhibits 83% correct
      classification for the EGG data, and has comparable performance with the BP
      network. This study demonstrates the potential of the neural network approach
      based on combined genetic algorithms with cascade correlation for diagnosis of
      gastric emptying from the EGG.

PMID- 10964044
TI  - Conceptual design of a combined device for normothermia and venous compression.
AB  - Hypothermia and venous thrombosis can cause complications during perioperative
      and postoperative periods which can even be fatal to patients' conditions.
      Separative devices have currently been used to prevent those two problems. The
      device proposed here is to combine in a simple unobtrusive fashion the desirable
      effects of both temperature control and deep venous thrombosis prophylaxis in
      perioperative patients. A design chart of the new device is provided and design
      issues are addressed.

PMID- 10964045
TI  - Nasopharyngeal carcinoma: the role of the dentist in assessment, early diagnosis
      and care before and after cancer therapy.
AB  - Nasopharyngeal carcinoma (NPC) may present first to the dental profession as
      facial pain, neck masses, difficulty in speech and swallowing, ear, nose and
      throat symptoms, or as symptoms of temporomandibular disorders (TMD). Recognition
      of the signs and symptoms are essential in order to lead to the correct
      diagnosis, and to avoid inappropriate intervention that may further delay
      diagnosis and initiation of treatment of the cancer. Differentiation between NPC
      and TMD may be facilitated by specific questioning of other symptoms that are not
      frequently associated with TMD such as neck masses, nasal obstruction, recent
      unilateral hearing deficit and epistaxis. The general dentist can become involved
      at three stages of a patient's experience with NPC: Stage 1, recognition of signs
      and symptoms; Stage 2, pre-treatment dental assessment; and Stage 3, post
      treatment support. This paper is intended to: (1) alert the general dentist of
      the signs and symptoms associated with NPC, such that timely and appropriate
      treatment may ensue; (2) provide a basic outline for assessment, preparation,
      palliation and continuing care of a patient diagnosed with NPC; and (3) underline
      the significant role of the general dentist in achieving an optimal quality of
      life for these patients

PMID- 10964046
TI  - Genetic aberrations in oral or head and neck squamous cell carcinoma 3: clinico
      pathological applications.
AB  - The molecular changes in malignant epithelium in the head and neck offer
      possibilities for the development of diagnostic, prognostic and other markers.
      This article reviews recent developments in this field.

PMID- 10964047
TI  - Head and neck in situ carcinoma: incidence, trends, and survival.
AB  - This analysis describes the epidemiology of in situ head and neck carcinomas
      (anatomic sites of lip, oral cavity, pharynx, larynx) about which there is
      limited knowledge. Data were derived from nine population-based cancer registries
      participating in the National Cancer Institute's Surveillance, Epidemiology and
      End Results (SEER) Program. SEER annual age-adjusted incidence rates for in situ
      head and neck carcinomas increased from 6.33/1,000,000 person-years (PY) in 1976
      to 8.04/1,000,000 PY in 1995 [percent change (PC)=35%, P<0. 001]. From 1976 to
      1995 age-adjusted changes in incidence by anatomic site ranged from 53% PC
      (larynx) to -11% PC (lip) (both P<0. 005). Incidence and survival associated with
      in situ head and neck carcinomas varied by anatomic site, age, sex, and race and
      did so in a pattern similar to that seen for invasive carcinomas of this region.
      However, the climbing incidence of in situ carcinoma, which may be related to
      increased surveillance, contrasts sharply with the declining incidence of
      invasive carcinoma.

PMID- 10964048
TI  - Metabolizing enzyme genotype and risk for upper aerodigestive tract cancer.
AB  - Genetic polymorphisms are associated with a number of enzymes involved in the
      metabolism of carcinogens important in the induction of upper aerodigestive tract
      cancer. It has been suggested that such polymorphisms may be linked to cancer
      susceptibility. Using a case-control molecular epidemiologic approach, the
      association between many of these genetic polymorphisms and susceptibility to
      upper aerodigestive tract cancer has been investigated in numerous studies. In
      this review, we summarize the findings of these studies, analyzing potential
      associations with upper aerodigestive tract cancer risk in terms of
      gene:environment interactions, genotype-induced functional defects in enzyme
      activity and/or expression, and the influence of race on these associations.

PMID- 10964049
TI  - Induction of the c-jun protooncogene expression by areca nut extract and
      arecoline on oral mucosal fibroblasts.
AB  - To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis,
      expression of c-fos and c-jun protooncogenes was examined in human oral mucosal
      fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found
      that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h
      induced about three-fold increase in c-jun mRNA levels. This increase was
      transient and the level of c-jun mRNAs returned rapidly to control levels
      thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at
      detectable levels. During AQ chewing, oral mucosal cells are continuously
      stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene
      by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral
      squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation
      of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L
      buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a
      minimal effect on arecoline-induced c-jun expression. Therefore, arecoline
      induced c-jun expression is independent of GSH depletion.

PMID- 10964050
TI  - Basic fibroblast growth factor and angiogenesis in squamous carcinoma of the
      tongue.
AB  - The relationship between basic fibroblast growth factor (bFGF), receptors for
      bFGF and neoangiogenesis was investigated in 51 patients with squamous cell
      carcinoma of the tongue, 26 of whom had metastatic disease in cervical lymph
      nodes. Vessels were demonstrated by immunocytochemical labelling for CD34 and
      expressed as raw counts and volume-weighted counts. bFGF protein and its
      receptors FGFR1(flg) and FGFR2(bek), were demonstrated using immunocytochemical
      labelling. In situ hybridisation for bFGF mRNA was performed using a 250-bp
      digoxigenin-labelled RNA probe. In normal epithelium, the expression of bFGF
      protein and mRNA was more intense in the basal layer, while receptors for bFGF
      were expressed more strongly in the superficial parts. In carcinomas, expression
      of bFGF was greater in the more poorly-differentiated cells, but showed no
      relation to the overall tumour differentiation. There was strong bFGF expression
      in tumour-infiltrating lymphocytes. The expression of bFGF receptors was
      variable, with FGFR2 being particularly high in areas of keratinisation. There
      were no consistent changes in bFGF or receptor expression between primary
      carcinomas and their lymph node metastases, and there was no correlation with
      measures of vascularity or tumour growth pattern. bFGF is synthesised by all
      squamous carcinomas and has the potential to modulate angiogenesis. However,
      these data suggest that changes in the expression of bFGF and its receptors are
      not related to the intensity of neoangiogenesis in lingual carcinomas or their
      nodal metastases.

PMID- 10964051
TI  - BAG-1 expression correlates highly with the malignant potential in early lesions
      (T1 and T2) of oral squamous cell carcinoma.
AB  - BAG-1 is a Bcl-2-binding protein that functions as an anti-apoptotic molecule. In
      this report we show a possible correlation between BAG-1 expression levels and
      the probability of oral squamous cell carcinoma (SCC) progression. We
      investigated BAG-1 expression levels in 22 patients diagnosed with early lesions
      (T1 and T2) of oral SCCs using immunohistochemistry and western blotting. High
      steady-state levels of BAG-1 were detected in 13 out of 22 cases (59%). High BAG
      1 expression was observed more frequently in cases with nodal metastasis (89%)
      than in those without nodal metastasis (38%) (P<0. 03), suggesting that BAG-1
      expression levels may correlate with the pathological stage of oral SCCs.
      Furthermore, BAG-1 expression levels correlated with the WHO grade, i.e. 45% in
      grade-I cases as opposed to 72% in grade-II cases (P<0.02). These data suggest
      that an analysis of BAG-1 expression may be useful in establishing a prognosis
      for patients with oral SCCs, and especially in predicting the metastatic
      potential of SSCs.

PMID- 10964052
TI  - Immunohistochemical evaluation of estrogen and progesterone receptors in adenoid
      cystic carcinoma of salivary gland origin.
AB  - Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin,
      which is characterized by a high rate of local recurrence and distant metastasis
      even after aggressive surgical treatment. In several studies using various
      immunohistochemical techniques, estrogen and progesterone receptor (ER and PgR)
      proteins in salivary gland ACC have been identified and the possible use of
      endocrine therapy as a treatment modality suggested. On this basis, 27 samples of
      formalin-fixed paraffin-embedded salivary gland ACC were immunohistochemically
      evaluated for the presence of ER and PgR. ER was not detected in any of the
      tumors and PgR was identified in only two cases. Thus, application of hormone
      therapy to salivary gland ACC is not supported by the results of the present
      study.

PMID- 10964053
TI  - Mucoepidermoid carcinoma of salivary glands in children and adolescents:
      assessment of proliferation markers.
AB  - Malignant neoplasms represent one-third of all pediatric salivary gland tumors.
      Mucoepidermoid carcinoma (MEC) composes 51% of malignant tumors and 16% of all
      salivary gland neoplasms in pediatrics. Prognostic factors in MEC in pediatric
      patients have not been well defined. Histopathologic features, clinical outcomes
      and proliferation markers in 26 pediatric patients (median age 11 years; 19F:7M)
      with salivary gland MECs were evaluated retrospectively. MEC histocytologic
      grading used a three-tiered system. Proliferation was assessed by determining the
      percentage of tumor cells immunoreactive for PCNA and Ki-67. Tumor site was 16
      parotid, eight submandibular, one base of tongue and one maxillary lip. Median
      tumor size was 2.5 cm (range 1.5-5 cm). MEC grade was nine low grade (LG), 15
      intermediate grade (IG) and two high grade (HG). Metastatic disease and capsular
      invasion occurred in five cases, while perineural invasion was noted in three
      cases. Mean percentage of tumor cells immunoreactive for proliferation markers is
      as follows: PCNA: LG 9%, IG 17%, HG 32%; and Ki-67: LG 7%, IG 12%, HG 26%.
      Treatment was surgical in 21 cases, and surgery with chemotherapy and
      radiotherapy in five cases. Two patients with high grade MECs died of disease
      (21, 44 months). Twenty-four patients had no evidence of disease at a median
      follow-up of 104 months (range 30-298 months). MECs were second malignancies in
      two children with prior radiotherapy and chemotherapy for leukemia and
      histiocytosis. Low and intermediate grade salivary gland MECS in a pediatric
      population may have a favorable outcome when compared with high grade MECs.
      Proliferation markers appear to be linked to histocytologic MEC grade and may
      provide information regarding biologic behavior of salivary gland MECs in
      children and adolescents.

PMID- 10964054
TI  - Squamous cell carcinoma of the superior gingivolabial sulcus.
AB  - The superior gingivolabial sulcus has not been recognised as a separate entity in
      the oral cavity for the localisation of carcinoma. These cancers are not
      uncommonly labelled as buccal carcinomas or as carcinomas originating from the
      superior alveolar process and sometimes as maxillary sinus carcinomas. Early
      symptoms of sensory disturbances are often missed. Although cervical nodal
      metastasis is not usual at first presentation, metastasis to parapharyngeal,
      retropharyngeal and nasolabial lymph nodes is known. This article presents the
      author's observations on carcinoma of the superior gingivolabial sulcus seen over
      a period of 4 years. Cancer at this site has poor prognosis. Despite aggressive
      treatment with radical locoregional surgery and postoperative radiotherapy, only
      one of nine patients survived 5 years.

PMID- 10964056
TI  - Percutaneous endoscopic gastrostomy at the time of tumour resection in advanced
      oral cancer.
AB  - The role of percutaneous endoscopic gastrostomy (PEG) in patients undergoing
      resection of head and neck malignancy is well established. The procedure may be
      performed pre- or post-operatively with intravenous sedation or alternatively
      under general anaesthesia at the time of tumour resection. There are concerns as
      to the safety of PEG, particularly when performed under intravenous sedation.
      Elderly patients with poor general health and those with airway compromise may be
      at significant risk. We believe that patients with advanced oral malignancy often
      fall into such groups and, therefore, we routinely perform PEG at the time of
      resection. The aim of this study was to determine the potential risk factors for
      PEG insertion in patients with advanced oral malignancy and present our
      experience with insertion at the time of resection. A retrospective study was
      undertaken of the risk factors for PEG insertion in 72 consecutive patients with
      stage IV oral cancer treated between April 1993 and March 2000. Age, sex, tumour
      site, past medical history, American Society of Anaesthesiologists (ASA) and
      laryngoscopy grade, as an assessment of potential airway compromise, were
      recorded. There were 72 patients, 40 males and 32 females, with a mean age of 63
      years (27-90). Eighteen patients (25%) scored 3 or 4 on the ASA scores of
      physical status. Laryngoscopy grades were recorded in 65 patients; of these, 18
      (25%) had reduced visualisation of the larynx and in two patients not even the
      epiglottis could be seen. It is concluded that patients with advanced oral cancer
      have significant risk factors for PEG placement. However, PEG can be safely
      performed at the time of ablative surgery and has the advantage of avoiding an
      additional operative event for the patient.

PMID- 10964055
TI  - Serum antioxidant micronutrients and the risk of oral leukoplakia among Japanese.
AB  - A population-based case-control study was designed for the investigation of any
      association between serum micronutrient levels and oral leukoplakia. Out of a
      total of 9536 subjects over the age of 40 years who participated in the oral
      mucosal screening programme in Tokoname city, 48 cases detected with oral
      leukoplakia (38 male:10 female) were recruited. For each case, four controls
      matched by age and sex were selected from the same cohort. We examined the
      fasting serum levels of retinol, alpha-tocopherol, zeaxanthin and lutein,
      cryptoxanthin, lycopene and carotenoids (alpha-carotene and beta-carotene) by
      high-performance liquid chromatography. Among males with leukoplakia mean serum
      lycopene and beta-carotene levels (0.175+/-0.202, 0.357+/-0.295 micromol/l) were
      significantly lower than those of controls (0.257+/-0.252, 0.555+/-0.408
      micromol/l) (P<0.05, P<0.005). Logistic regression analysis with leukoplakia as
      the dependent variable showed that high serum levels of beta-carotene were
      related to low risk of oral leukoplakia (odds ratio 0.160, 95% C.I.: 0.029-0.866,
      P<0.05). There were no significant differences in any of the serum nutrients
      estimated in female subjects. Our results suggest for the first time that high
      serum levels of beta-carotene may provide protection against oral precancer for
      the Japanese male.

PMID- 10964057
TI  - Gene expression profiles in squamous cell carcinomas of the oral cavity: use of
      laser capture microdissection for the construction and analysis of stage-specific
      cDNA libraries.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      among men in the developed world affecting the oral cavity, salivary glands,
      larynx and pharynx. Utilizing tissue from patients with HNSCC, we sought to
      systematically identify and catalog genes expressed in HNSCC progression. Here,
      we demonstrate the successful use of laser capture microdissection for procuring
      pure populations of cells from patient tissue sets comprised of oral squamous
      cell carcinomas (OSCCs) and matching normal tissue. From the estimated 5000 cells
      procured for each sample, we were able to extract total RNA (14.7-18.6 ng) of
      sufficient quality to transcribe GAPDH by reverse transcriptase-polymerase chain
      reaction (RT-PCR). The RNA was used for the synthesis of blunt-ended, double
      strand complementary DNAs (cDNAs) by oligo (dT)-mediated reverse transcription,
      followed by addition of linkers. Primers specific for these linkers with uracil
      deglycosylase-compatible ends were used to amplify these cDNAs by PCR and the
      product was subcloned into the pAMP10 cloning vector. Ninety-six clones from each
      of six libraries were randomly sequenced and results indicated that 76-96% of the
      inserts represent either anonymous expressed sequence tags (ESTs) (25-48%), known
      genes (9-29%) or novel sequences (27-51%), respectively, with very little
      redundancy. These results demonstrate that high quality, representative cDNA
      libraries can be generated from microdissected OSCC tissue. Furthermore, these
      finding suggest the existence of at least 132 novel genes expressed in our cDNA
      libraries, which may have a role in the pathogenesis of HNSCC, and may represent
      novel markers for early detection as well as targets for pharmacological
      intervention in this disease.

PMID- 10964058
TI  - Microsatellite alterations in squamous cell carcinoma of the head and neck -
      clustering of loss of heterozygosity in a distinct subset.
AB  - Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been
      recognized as important events in the carcinogenesis of many cancers, including
      squamous cell carcinoma of head and neck (SCCHN). However, microsatellite
      alterations have not been documented in SCCHN from Chinese patients. We
      investigated the frequency and clinical significance of LOH and MSI in 30 SCCHN
      from Hong Kong Chinese using polymerase chain reaction on 17 microsatellite
      markers on chromosomes 3p, 4q, 7q, 9p, 17p and 18q. LOH was present in nine
      tumours (30%) and MSI in four (13%). The incidence of LOH (7/13; 53.8%) in
      hypopharyngeal-laryngeal cancers was significantly higher than that (2/17; 11.8%)
      in the oral cancers (P=0.020). LOH was more often detected at the loci on
      chromosomes 7 and 9. Patients with tumours having LOH had slightly poorer outcome
      compared with those without, although the differences did not reach statistical
      significance. Our data show that the incidence of microsatellite alterations in
      SCCHN from Hong Kong Chinese is low. However, LOH may be one of the genetic
      mechanisms in the carcinogenesis of a subset of SCCHN (hypopharyngeal-laryngeal
      cancers).

PMID- 10964059
TI  - Intra-alveolar granulocytic sarcoma developing after tooth extraction.
AB  - Granulocytic sarcoma (GS) is a malignant tumour composed of poorly differentiated
      myeloid cells forming in an extramedullary site. It is generally associated with
      acute leukaemia, particularly the myelocytic type. Its appearance in patients
      with chronic myeloid leukaemia is exceptional. GS can appear in multiple
      locations with the oral cavity being rarely involved. A mandibular GS detected in
      a patient with chronic myeloid leukaemia 10 days after a tooth extraction is
      reported. The pathogenesis (by metastatic cells or migration through the
      Haversian canals) of the tumour is discussed.

PMID- 10964060
TI  - Spindle-cell lipoma of the cheek: a case report.
AB  - Spindle-cell lipoma (SCL) is a distinct histological variant of lipoma.
      Clinically, it appears as a solitary, subcutaneous, circumscribed lesion. SCL
      accounts for about 1.5% of all adipocytic tumours. Only nine cases of intraoral
      SCL were found in the literature. Microscopically, mature adipocytes and spindle
      cells are immersed in a myxoid stroma. SCL needs only local excision, and it does
      not recur.

PMID- 10964061
TI  - Syringomyelia presenting as ulnar neuropathy at the elbow.
AB  - OBJECTIVES: Syringomyelia may present with confusing, unilateral patterns of
      segmental muscle involvement and dissociated sensory loss. The objective of this
      study was to report a patient with Chiari malformation type 1 (CM1) and
      syringomyelia who had an unusual presentation suggesting ulnar neuropathy at the
      elbow. RESULTS: A 24-year-old woman presented with clinical evidence of ulnar
      neuropathy at the elbow except that there was disproportionate abductor digiti
      mini (ADM) atrophy and weakness, equivocal ipsilateral abductor pollicis brevis
      weakness and hyporeflexia in both arms. Nerve conduction studies revealed marked
      amplitude reduction of the left ulnar ADM-compound muscle action potential (ADM
      CMAP) with a normal first dorsal interosseous-CMAP amplitude, no focal slowing or
      conduction block, and a normal ulnar sensory response amplitude. Electromyography
      (EMG) showed multi-segmental, left C7-T1 fibrillations and chronic reinnervation
      changes. Magnetic resonance imaging (MRI) of the cervical spine demonstrated CM1
      and syringomyelia. CONCLUSIONS: Syringomyelia may clinically mimic ulnar
      neuropathy at the elbow.

PMID- 10964062
TI  - Working memory dysfunction in major depression: an event-related potential study.
AB  - OBJECTIVES: To study working memory function in untreated major depression using
      a digit probe identification and matching task. METHODS: We compared behavioural
      performance and event-related potentials during processing of the Sternberg
      working memory task in 14 depressed patients and 14 healthy matched control
      subjects. RESULTS: Patients made more mistakes than controls as the memory load
      was increased from one to 5 digits and had significantly slower reaction times at
      all levels of memory load. The patients' event-related potentials (ERPs) differed
      significantly from controls. Pathological changes were similar for auditory and
      visual presentation. Surface negative activity in the 157-210 ms section of the
      waveform was reduced for all levels of memory load, suggesting abnormal
      sensory/perceptual processing in the modality-specific association cortices,
      possibly due to a failure of selective attention mechanisms. In the 375-840 ms
      epoch, the patients' responses showed large amplitude sustained negative
      activity, maximal at Cz and a reduced late positive wave. The large prolonged
      negativity in the patients' ERPs suggests activation of additional neuronal
      assemblies than those normally participating in the task. This could reflect
      either compensatory mechanism or dysfunction of inhibitory systems. These changes
      were sensitive to memory load, suggesting that they reflect alterations of memory
      related processes. CONCLUSIONS: This study provides objective evidence that major
      depression significantly affects working memory. The ERP changes in depression
      could be accounted for by dysfunction of the central executive control of working
      memory.

PMID- 10964063
TI  - Concurrent recording of steady-state and transient event-related potentials as
      indices of visual-spatial selective attention.
AB  - OBJECTIVES: The present study investigated the effects of spatial attention on
      concurrently recorded visual event-related potentials (ERPs) and steady-state
      visual evoked potentials (SSVEPs) to isoluminant color changes embedded in
      rapidly flickering stimuli. METHODS: EEG was recorded while subjects attended to
      flickering LEDs in either the right or left visual hemifield and responded by a
      button press to isoluminant color changes (targets). RESULTS: Target isoluminant
      color changes elicited the typical ERP components P1, N1, N2 and P3, which were
      enhanced for attended targets compared to unattended targets. Consistent with
      previous findings, SSVEP amplitude was enlarged for attended flicker stimuli at
      posterior electrode sites contralateral to the attended visual hemifield. In
      addition, significant correlations were found between the N1, N2 and the SSVEP
      attention effects, whereas no such correlations were found between the P1, P3 and
      SSVEP attention effects. CONCLUSIONS: Results suggest that the SSVEP and ERP
      reflect partially overlapping attentional mechanisms that facilitate the
      discriminative processing of stimuli at attended locations.

PMID- 10964064
TI  - Individual differences in mismatch negativity measures of involuntary attention
      shift.
AB  - OBJECTIVE: The purpose of this study was to compare the automatic detection of
      deviance in introverts and extraverts. Event-related potentials were recorded to
      standard and deviant stimuli. These were presented either rapidly or slowly.
      Stimuli that are presented slowly may intrude into consciousness. METHODS: Twenty
      subjects were tested and divided into introverted and extraverted groups. A 500
      Hz standard stimulus was presented on 85% of trials. On the remaining 15% of
      trials, a 750 Hz deviant was presented. In separate conditions, stimuli were
      presented rapidly (every 500 ms) or slowly (every 1500 ms). Subjects ignored the
      stimuli while reading. RESULTS: The deviant stimulus elicited a mismatch
      negativity (MMN) in both conditions. No inter-group differences in the MMN
      emerged when a rapid rate of presentation was employed. When a slower rate was
      employed, a late negativity was significantly larger for the extraverted than the
      introverted group. This was followed by a late positive wave. CONCLUSION: The
      late negative-positive complex is thought to reflect intrusiveness. It would
      therefore appear that extraverts are more distractible than introverts when
      stimuli are presented slowly.

PMID- 10964065
TI  - Thermal thresholds in complex regional pain syndrome type I: sensitivity and
      repeatability of the methods of limits and levels.
AB  - OBJECTIVES: To study whether the method of levels (MLE) or the method of limits
      (MLI) is preferable as a method of measuring thermal perception thresholds in
      patients with complex regional pain syndrome type I (CRPS I). METHODS: Perception
      thresholds for warmth and cold were measured twice, with both MLE and MLI, at a 1
      month interval, both at unaffected and affected wrists (n=33) or feet (n=20) of
      patients with CRPS I of one extremity. RESULTS: (1) Sensitivity for pathology was
      equal for both methods. (2) The agreement between thresholds measured by both
      methods was low at all locations, except for the unaffected wrist. Since
      thresholds measured with the MLI always contain reaction time artefacts, this
      lack of agreement favours the MLE. (3) At both unaffected and affected wrists,
      the MLE showed significantly better coefficients of repeatability as compared to
      the MLI for both sensations. However, at both unaffected and affected feet, there
      was no preference for either method as far as threshold measurement repeatability
      was concerned. CONCLUSIONS: Abnormal thermal perception thresholds occurred in
      20% (foot) to 36% (wrist) of the CRPS I patients on the affected side and in 15%
      (foot, wrist) on the unaffected side. The MLE is considered to be the preferable
      method to assess thermal perception thresholds in CRPS I.

PMID- 10964066
TI  - Spectro-temporal analysis of complex tones: two cortical processes dependent on
      retention of sounds in the long auditory store.
AB  - OBJECTIVES: To examine whether two cortical processes concerned with spectro
      temporal analysis of complex tones, a 'C-process' generating CN1 and CP2
      potentials at cf. 100 and 180 ms after sudden change of pitch or timbre, and an
      'M-process' generating MN1 and MP2 potentials of similar latency at the sudden
      cessation of repeated changes, are dependent on accumulation of a sound image in
      the long auditory store. METHODS: The durations of steady (440 Hz) and rapidly
      oscillating (440-494 Hz, 16 changes/s) pitch of a synthesized 'clarinet' tone
      were reciprocally varied between 0.5 and 4.5 s within a duty cycle of 5 s.
      Potentials were recorded at the beginning and end of the period of oscillation in
      10 non-attending normal subjects. RESULTS: The CN1 at the beginning of pitch
      oscillation and the MN1 at the end were both strongly influenced by the duration
      of the immediately preceding stimulus pattern, mean amplitudes being 3-4 times
      larger after 4.5 s as compared with 0.5 s. CONCLUSIONS: The processes responsible
      for both CN1 and MN1 are influenced by the duration of the preceding sound
      pattern over a period comparable to that of the 'echoic memory' or long auditory
      store. The store therefore appears to occupy a key position in spectro-temporal
      sound analysis. The C-process is concerned with the spectral structure of complex
      sounds, and may therefore reflect the 'grouping' of frequency components
      underlying auditory stream segregation. The M-process (mismatch negativity) is
      concerned with the temporal sound structure, and may play an important role in
      the extraction of information from sequential sounds.

PMID- 10964067
TI  - Single unit responses of human cutaneous mechanoreceptors to air-puff
      stimulation.
AB  - OBJECTIVE: To investigate responsiveness of human cutaneous mechanoreceptor to
      selective tactile stimuli produced by brief air-puff stimulation. METHODS: Using
      percutaneous microneurography, activities of single sensory units innervating
      glabrous skin of the hand were recorded, and air-puff stimuli with a short rise
      time (0.5 ms), generated by a high-speed air control system, were applied to the
      receptive field. Receptor activation time was estimated as the latency difference
      between electrically and air-puff evoked responses. RESULTS: Thirty units were
      analyzed: all 4 kinds of mechanoreceptors of human glabrous skin (fast adapting
      type 1 [FA I, n=7], fast adapting type 2 [FA II, n=4], slowly adapting 1 [SA I,
      n=5] and slowly adapting 2 [SA II, n=14]) were activated by air-puff stimulation.
      Estimated receptor activation times were 0.6-6.2 ms (mean 2.2 ms). FA II units
      occasionally responded twice or more to a single air-puff stimulus. CONCLUSIONS:
      Brief air-puffs can activate all 4 human cutaneous mechanoreceptors, and the
      receptor transduction time is estimated as approximately 2.0 ms. Properties of
      human mechanoreceptors can be studied using air-puff stimulation and
      microneurography.

PMID- 10964068
TI  - Visual electrophysiological responses in subjects with cerebral autosomal
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
AB  - OBJECTIVES: To evaluate visual electrophysiological responses in subjects with
      cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL). METHODS: Three subjects (one male and two females, mean age 55.3+/-2.9
      years) belonging to an Italian family already diagnosed with CADASIL through
      clinicopathological and genetic studies and 14 control subjects (6 males and 8
      females, mean age 52.7+/-3.6 years) were enrolled in the study. Flash
      electroretinogram (ERG), oscillatory potentials (OPs) and simultaneous recordings
      of pattern electroretinogram (PERG) and visual evoked potentials (VEPs) were
      assessed in all 3 subjects with CADASIL and age-matched controls. RESULTS:
      Subjects with CADASIL showed: reduced ERG, OP and PERG (N35-P50, P50-N95)
      amplitudes with respect to our normal limits; delayed PERG (N35, P50) and VEP
      (P100) implicit times when compared with our normal limits; and VEP (N75-P100)
      amplitudes and retinocortical times within our normal limits. CONCLUSIONS:
      Subjects with CADASIL present a dysfunction in the outer, middle and innermost
      retinal layers when the index of neural conduction in the postretinal visual
      pathways is normal. The delay in visual cortical responses observed in subjects
      with CADASIL may be ascribable to retinal impairment with a possible functional
      sparing of the postretinal visual structures.

PMID- 10964069
TI  - The effects of nicotine on the 13 Hz steady-state visually evoked potential.
AB  - OBJECTIVES: The high alpha/low beta range of the spontaneous EEG appears to be
      particularly sensitive to the effects of nicotine. The present study examined the
      acute effects of nicotine on the topography of the 13 Hz steady-state visually
      evoked potential (SSVEP). METHODS: Thirteen moderate smokers participated in a
      repeated-measures design. The amplitude and latency of the SSVEP elicited by an
      unstructured sinusoidal 13 Hz flicker following a <0. 05 mg nicotine cigarette
      were compared to those following a 0.8 mg nicotine cigarette. RESULTS: The
      nicotine condition was associated with an increase in the amplitude of the SSVEP,
      when compared to the placebo condition, and this increase was greatest in central
      and right parietal regions. The latency of the SSVEP was reduced in the nicotine
      condition in bilateral frontal and right parietal regions. CONCLUSIONS: These
      results are similar to the effects of nicotine seen in studies examining
      spontaneous EEG, and are consistent with other studies indicating that the 13 Hz
      SSVEP indexes brain electrical activity in the high alpha/low beta range. The
      findings are discussed in terms of possible functional significance of nicotine
      induced cortical activation in this frequency range.

PMID- 10964070
TI  - Absent innervation of skin and sweat glands in congenital insensitivity to pain
      with anhidrosis.
AB  - OBJECTIVES: A case of a 10-year-old girl with congenital insensitivity to pain
      with anhidrosis (CIPA) is reported. METHODS AND RESULTS: Parents referred several
      hyperpyretic episodes without sweating occurring since birth, and insensitivity
      to pain, noticed when the child was 2 years old. Her body had many bruises and
      scars, bone fractures and signs of self-mutilation. Neurological examination was
      normal except for insensitivity to pain. Her IQ was 52. Electrical and tactile
      sensory nerve conduction velocities were normal. The patient was unable to detect
      thermal stimuli. Histamine injection evoked a wheal but not a flare; pilocarpine
      by iontophoresis did not induce sweat. Microneurography showed neural activity
      from A-beta sensory fibers while nociceptive and skin sympathetic C fiber nerve
      activity was absent. No small myelinated fibers and very rare unmyelinated fibers
      were found in the sural nerve. Immunohistochemistry showed a lack of nerve fibers
      in the epidermis and only few hypotrophic and uninnervated sweat glands in the
      dermis. CONCLUSIONS: The lack of innervation of the skin (C and A-delta fibers)
      appears to be the morphological basis of insensitivity to pain and anhidrosis,
      and is consistent with the loss of unmyelinated and small myelinated fibers in
      the sural nerve biopsy.

PMID- 10964071
TI  - Circadian and hypothermia-induced effects on visual and auditory evoked
      potentials in multiple sclerosis.
AB  - OBJECTIVES: Body cooling has been proposed as a symptomatic treatment for
      multiple sclerosis. This study aimed to assess the effects of body cooling and of
      circadian variations on clinical parameters and on visual and auditory evoked
      potential measures in multiple sclerosis patients. METHODS: Clinical status was
      assessed and VEPs, BAEPs and MLAEPs (all with two stimulus frequencies) were
      recorded a total of 4 times on two separate days (two times per day at 08:30 and
      15:00 h each day) in 10 multiple sclerosis patients and 10 controls. On one of
      these days, the subjects were submitted to body cooling before the afternoon
      session. RESULTS: Tympanic temperature was significantly higher in the afternoon.
      Cooling lowered the temperature by 1.4 degrees C. No clinical effects were
      observed. Circadian effects were detected on VEP amplitude, which increased both
      in controls and in patients at low stimulus frequency (P<0.01), and increased in
      controls and decreased in patients at high stimulus frequency (interaction:
      P<0.01). Cooling determined an increase in BAEP I-V peak-to-peak time in
      controls, and a reduction in patients at high stimulus frequency (interaction:
      P<0.01). In patients, cooling also determined a great increase in MLAEP amplitude
      (interaction: P<0.001). We did not find cooling effects on VEP measures.
      CONCLUSIONS: Visual and auditory evoked potentials showed differences in
      circadian and cooling effects between controls and multiple sclerosis patients.
      These differences are consistent with the hypothesis of temperature-dependent
      conduction blocks in demyelinated fibers. Cooling may have a clinical effect in
      selected patients only.

PMID- 10964072
TI  - Vibratory stimulation of proximal muscles does not affect cortical components of
      somatosensory evoked potential following distal nerve stimulation.
AB  - OBJECTIVES: The effects of the proprioceptive activity of the proximal muscles on
      somatosensory evoked potentials (SEPs) were investigated, using vibratory
      stimulation of proximal muscle tendons. METHODS: SEPs were recorded following
      electrical median nerve stimulation at the wrist during vibratory stimulation of
      tendon of pronator teres, biceps and trapezius muscles and fingers in 8 normal
      subjects. RESULTS: The cortical SEP components, N20, P25 and N33 recorded from
      the parietal area, and P20 and N30 recorded from frontal area contralateral to
      the stimulated side, were markedly attenuated by vibratory stimulation applied to
      the fingers, but unaffected by vibratory stimulation of the proximal muscles.
      CONCLUSION: The proprioceptive afferent, especially group Ia muscle spindle
      afferent, in the relaxed proximal muscles is not likely to contribute to the
      gating of SEP following distal nerve stimulation.

PMID- 10964073
TI  - Cardiac activation during arousal in humans: further evidence for hierarchy in
      the arousal response.
AB  - OBJECTIVES: One major subject of discussion in sleep studies is whether bursts of
      K-complexes (K-bursts) and delta waves (D-bursts), expressions of a subcortical
      arousal, truly reflect an arousal response during sleep. To address this question
      we studied the changes in heart rate (HR) during spontaneous arousals in healthy
      subjects. METHODS: Twenty-seven healthy adults were examined. Arousals were
      graded in 4 levels, including the standard definition of a microarousal (MA),
      phases of transitory activation (PAT), D-bursts and K-bursts. HR was analyzed for
      10 beats before and 20 beats during arousal. EEG spectral analysis was performed
      for all types of arousals, including in the analysis the 20 s period preceding
      the actual event. RESULTS: Each type of arousal was associated with HR changes
      consisting of a tachycardia followed by a bradycardia. Changes were more
      pronounced during MA and PAT. Detailed analysis of the HR response showed that HR
      always increased before MA and PAT onset, associated with a rise in delta, theta
      and fast EEG activities, and suggesting a cerebral activation. CONCLUSIONS: Our
      data suggest that such subcortical arousals represent a real arousal response
      inducing cardiac activation similar to that found during MA and PAT. During MA
      and PAT, a rise in HR appears before the onset of the actual arousal associated
      with an increase in EEG slow and fast activity. The link between EEG and HR
      variation during MA and PAT and the fluctuations in HR during subcortical arousal
      suggest a continuous spectrum in the arousal mechanisms, starting at the
      brainstem level and progressing to cortical areas.

PMID- 10964074
TI  - Observation of EEG coherence after repetitive transcranial magnetic stimulation.
AB  - OBJECTIVE: The effects before and after repetitive transcranial magnetic
      stimulation (rTMS) on EEG activity were investigated. METHODS: Nineteen healthy
      subjects received two trains (10 Hz, 100% of motor threshold, 3 s/train) of rTMS
      to the left frontal area. Directed coherence and ordinary coherence were
      calculated from EEG epochs recorded before and after (1 approximately 3 and 3
      approximately 5 min) rTMS. The results were compared and demonstrated on maps.
      RESULTS: Directed coherence between cortical areas increased after rTMS (F=5.62,
      P<0.005), with the intra-hemispheric change being more pronounced than the inter
      hemispheric change. Connections from the stimulated site to other sites were
      selectively reinforced. In contrast, ordinary coherence did not change after the
      stimulation. rTMS did not influence the dominant frequency at which maximal
      coherence was calculated. Differences in the directed coherence with opposite
      directions after rTMS were significantly correlated with the differences before
      rTMS (r=0.88, 0.89, P<0.001). CONCLUSIONS: (1) rTMS can enhance the connections
      between cortical areas, especially connections between the stimulated cortex and
      other sites in the brain. (2) Comparing with connections from the parietal area
      to frontal area, connections from the frontal area to parietal area are obviously
      improved by rTMS in both hemispheres. (3) The effects of rTMS can last for
      several minutes. Therefore, the necessity of EEG monitoring in rTMS studies is
      suggested.

PMID- 10964075
TI  - Does a peculiar EEG pattern exist also for FRAXE mental retardation?
AB  - OBJECTIVE: FRAXE mental retardation, a recently identified rare genetic
      condition, is due to a mutation of the FMR2 gene, located at Xq28 region. The
      phenotype is non-specific and characterized by developmental delay, speech,
      reading and writing problems, poor adaptive skills, anxiety, aggressiveness,
      obsessive-compulsive disturbance, and hyperactivity. The objective of this study
      was to describe the characteristic EEG pattern found in one patient with FRAXE
      mental retardation. METHODS: EEG (with photic stimulation and hand/foot tapping)
      and median nerve somatosensory evoked potentials were recorded in a 8-year-old
      male patient with FRAXE mental retardation (diagnosis confirmed by molecular
      genetic analysis) and speech disturbances. RESULTS: The patient never presented
      seizures; however, sleep enhanced multifocal spikes were found in the EEG.
      Moreover, tactile stimulation of hands and feet, as well as intermittent photic
      stimulation, provoked the appearance of spikes. Somatosensory evoked potentials
      from the median nerves showed a 'giant' component at around 60 ms. CONCLUSIONS:
      Considering the rarity of both FRAXE mental retardation and tactile evoked
      spikes, their association in the same subject might be considered as not casual.
      If confirmed by future studies, these neurophysiological findings might be
      considered as a marker for FRAXE mental retardation.

PMID- 10964076
TI  - Gabapentin-induced modulation of interictal epileptiform activity related to
      different vigilance levels.
AB  - OBJECTIVES: Gabapentin (GBP) is a novel antiepileptic drug (AED), currently used
      as add-on therapy in patients with partial seizures. Similar to other AEDs,
      little is known about its effects on nocturnal sleep, despite the strict
      relationship between sleep and epileptic discharges. The aim of our study was to
      evaluate the effects of chronic therapy with GBP on both nocturnal sleep and on
      interictal epileptiform abnormalities (IEA) in relation to the different sleep
      stages. METHODS: Eighteen patients affected by partial seizures resistant to
      common AEDs were submitted to nocturnal polygraphic recordings under baseline
      conditions and after 4 months of add-on GBP treatment. RESULTS: We observed a
      significant increase in unilateral/focal IEA during light NREM sleep and a
      significant reduction in bilateral/diffuse IEA during wakefulness after sleep
      onset (WASO) with respect to the baseline condition. A significant increase in
      REM sleep and slow wave sleep (SWS) associated with a reduction in the number of
      awakenings and Stage 1 was also observed after GBP chronic therapy. CONCLUSIONS:
      GBP therapy improves the sleep pattern of epileptic patients and it seems to
      modulate the expression of IEA with different effects in relation to the various
      vigilance levels.

PMID- 10964077
TI  - Quantitative analysis of EEG background activity in patients with rolandic
      spikes.
AB  - OBJECTIVE: The aim was to compare the background activity, through quantitative
      EEG analysis, of patients with rolandic spikes and normal age-matched controls.
      MATERIAL AND METHODS: Twenty-one channel EEG of 23 children with rolandic spikes
      and 39 normal children, with ages ranging from 7 to 12 years, were submitted to
      quantitative analysis (FFT) of discharge-free epochs. Patients and controls were
      divided in groups according to age (7-9 and 10-12 years old). Delta, theta, alpha
      and beta frequency ranges were compared between groups for all electrode
      positions. RESULTS: Comparing normals, the 7-9 years old group showed power
      reduction in the alpha and beta ranges. Comparing patients and normal age-matched
      groups, the patients showed power increase, at all frequency ranges in the 7-9
      years old group and at delta and theta frequency ranges in the 10-12 years old
      group. CONCLUSIONS: Our findings agree with recent evidences that these children
      may differ from normal (besides the eventual occurrence of seizures); but they
      also suggest that these differences can be related to immaturity and not
      necessarily related to the epileptiform discharge.

PMID- 10964078
TI  - Duration of rhythmic EEG patterns in neonates: new evidence for clinical and
      prognostic significance of brief rhythmic discharges.
AB  - OBJECTIVE: This study aimed at identifying the characteristics - especially the
      duration - of rhythmic discharges in neonatal EEG, and their association with
      clinical neonatal problems. Specifically, we aimed at testing the diagnostic and
      prognostic validity of using 10 s as minimal duration for defining
      electroencephalographic seizures. DESIGN AND METHODS: The polysomnographies of
      340 neonates were reviewed, and episodes of rhythmic discharges were identified,
      analyzed, and quantified. The study sample was divided into 3 groups: one in
      which the maximal duration of rhythmic discharges was shorter than 10 s (brief
      rhythmic discharges, BRD), a second one in which there were rhythmic discharges
      longer than 10 s (long rhythmic discharges, LRD), and finally a group in which no
      rhythmic discharge was found (No-RD). These 3 groups of subjects were compared
      for the baseline and outcome clinical data. RESULTS: From the 340 neonates
      studied, 210 did not present any form of rhythmic discharge, 67 (19. 7%) had only
      BRD episodes, and 63 (18.5%) had at least one LRD episode. Prevalence of rhythmic
      discharges was low among healthy full term newborns, and was significantly higher
      among preterm and high-risk newborns. Electrophysiological characteristics of
      rhythmic discharges did not differ between healthy neonates and high-risk ones.
      Accompanying clinical manifestations were present in 26.3% of the LRD group, but
      also in 15.9% of the BRD group. The presence of BRD was significantly associated
      with leukomalacia and with hypoglycemia in the cross-sectional analysis of
      baseline data, and with an increased risk for abnormal neurodevelopmental outcome
      after a mean follow-up period of 47 months (adjusted relative risk=4.90, P<0.01).
      CONCLUSIONS: The present data demonstrate an association between BRD and clinical
      history of hypoxic-ischemic encephalopathy, especially when complicated by
      leukomalacia, and also with a prognosis of increased risk for abnormal
      neurodevelopmental outcome. The clinical and prognostic significance of isolated
      BRD justifies the need to include these brief episodes in future studies of
      neonatal seizures.

PMID- 10964079
TI  - Delayed facilitation of motor cortical excitability following repetitive finger
      movements.
AB  - OBJECTIVES: To define motor cortical excitability changes occurring at various
      times after non-fatiguing bimanual exercise of the index fingers. METHODS: Twenty
      healthy right-handed subjects were studied with transcranial magnetic stimulation
      (TMS) of the right non-dominant hemisphere. They performed regular (3-4/s)
      repetitive opening-closing bilateral movements of the index finger onto the
      thumb. Motor evoked potentials (MEPs) of the left first dorsal interosseus (FDI)
      and rate of the repetitive finger movements were determined (1) before exercise,
      (2) immediately following 3 exercise periods of 30, 60 and 90 s, and (3) over a
      subsequent 30 min rest period. RESULTS: Rate of movement did not show significant
      change during any of the exercise periods but did increase significantly when
      tested after 15 min of rest. MEPs immediately after 30 and 60 s of exercise were
      facilitated whereas MEPs after 90 s of exercise did not differ from baseline
      measures. MEP amplitudes were significantly increased after rest of approximately
      15 min compared to the baseline MEPs. In contrast, motor potentials evoked by
      peripheral nerve stimulation were unchanged throughout the experimental test
      periods. CONCLUSIONS: Motor cortical excitability relating to an intrinsic finger
      muscle (FDI) was facilitated beginning 15 min after a brief period of non
      forceful, repetitive activity of that muscle. This delayed facilitation of motor
      cortex after exercise may represent a form of short-term potentiation of motor
      cortical excitability.

PMID- 10964080
TI  - Impaired proactive and reactive grip force control in chronic hemiparetic
      patients.
AB  - OBJECTIVES: The aim of the study was to test manipulative capacities of
      hemiparetic patients with partial recovery in a drawer task. The main objective
      was to assess adjustments of grip force in the face of load perturbations.
      METHODS: The task was to pull and to hold the drawer manipulandum during
      predictable or unpredictable perturbations with short (90 ms) load pulses (factor
      set). RESULTS: The following novel observations were made. (1) Load pulses
      elicited, at a latency of about 70 ms, a transient grip force response and a
      corresponding phasic EMG response. These reactive adjustments were larger during
      holding than during pulling (factor task). In patients, the reactive grip force
      adjustments and the EMG response in the grip muscles were reduced. (2) The above
      deficit was set-dependent. (3) With regular perturbations, grip force was scaled
      already before perturbation onset. This proactive adjustment was greatly reduced
      in the patient group. (4) Coordination between grip force and pull force before
      onset of the perturbation was also disturbed in the patients who generated less
      grip force per unit pull force than control subjects. CONCLUSIONS: It is
      concluded that the patients had difficulties in adapting proactively and
      reactively to external load disturbances, in addition to their hand weakness.

PMID- 10964081
TI  - Short latency trigemino-sternocleidomastoid response in muscles in patients with
      spasmodic torticollis and blepharospasm.
AB  - OBJECTIVES: To further elucidate the pathogenesis of focal dystonias. METHODS:
      Short latency responses can be recorded in tonically active sternocleidomastoid
      muscles after stimulation of the infraorbital branch of the trigeminal nerve.
      Such trigemino-sternocleidomastoid response consists of a bilateral
      positive/negative wave in the average of unrectified surface EMG, corresponding
      to a short period of inhibition of motor unit firing. This brain stem reflex was
      investigated in 10 normal subjects, in 16 patients affected by spasmodic
      torticollis (ST) and in 10 patients with blepharospasm (BSP). RESULTS: All ST
      patients presented abnormalities of SCM responses after infraorbital nerve
      stimulation. The abnormalities were bilateral in all but one of the patients and
      were independent from previous treatment with botulinum toxin. No BSP patients
      showed alterations of this reflex. CONCLUSIONS: Abnormalities of brain stem
      interneurons which are responsible for oligosynaptic exteroceptive suppression
      reflexes occur specifically in ST. These findings further support the relevance
      of sensory inputs in the determinism of focal dystonias.

PMID- 10964082
TI  - Gait analysis in idiopathic normal pressure hydrocephalus--which parameters
      respond to the CSF tap test?
AB  - OBJECTIVES: Normal pressure hydrocephalus (NPH) is an often underestimated cause
      of hypokinetic gait disorders in the elderly. Diagnosing NPH is a complex
      problem, since many symptoms overlap with other neurological diseases. The
      purpose of the present study was to characterize the gait pattern in NPH
      quantitatively. Additionally, we analyzed the improvement of gait parameters
      following tapping of cerebrospinal fluid (CSF). METHODS: Gait analysis was
      performed in 10 patients and 12 age-matched healthy controls during overground
      and treadmill locomotion. RESULTS: Compared to healthy controls, patients with
      NPH walked significantly slower, with shorter and more variable strides and a
      somewhat lower cadence. The feet were not lifted to a normal height and the
      dorsal extension of the forefoot prior to heel-strike was insufficient. Balance
      related gait parameters such as step width and the foot rotation angles were
      significantly increased in NPH, while their variability was lower. Only some gait
      parameters improved after tapping 30 ml CSF. Gait velocity increased by about 23%
      due to an increased stride length, while the cadence remained unchanged. Balance
      related gait parameters and the foot-to-floor clearance during swing were not
      affected by the treatment. CONCLUSIONS: In conclusion, we found a triad of
      decreased stride length, decreased foot-to-floor clearance and a broad-based gait
      to be the typical features of the gait abnormality in NPH. Only the stride length
      improved following a diagnostic spinal tap. These results may help to more
      reliably diagnose the condition of NPH in a routine clinical setting.

PMID- 10964083
TI  - Motor evoked potential studies in Creutzfeldt-Jakob disease.
AB  - OBJECTIVES: Motor evoked potentials (MEPs) were recorded in 7 cases of
      Creutzfeldt-Jakob disease (CJD) to asses the involvement of pyramidal motor
      pathways in these cases. The diagnosis of CJD was confirmed by autopsy in 5 cases
      and based on clinical data in two cases. METHODS: Transcranial (MEP-cortex), root
      magnetic (MEP-root) and electrical stimulation of peripheral nerves (F-wave,
      direct M-response) were performed. The cortical excitability threshold, F-wave
      frequency, MEP amplitudes, peripheral motor conduction velocity, standardized
      distal latencies and central, root, and F-wave conduction times were evaluated.
      RESULTS: The results of MEP testing were markedly abnormal. Cortical excitability
      thresholds were elevated, MEP amplitudes were reduced while the conduction
      function was rather preserved. The features of functional disturbances and/or
      loss of upper and lower motor neurons were revealed. They correlated with the
      advancement of key clinical CJD symptoms (progressive dementia, extrapyramidal
      and cerebellar signs, myoclonic jerks, mutism and typical periodic EEG changes),
      while motor lesion signs might only be slight or absent. CONCLUSIONS: Conduction
      slowing, if present, seemed to be secondary to axonal lesion.

PMID- 10964084
TI  - Neurophysiological follow-up of motor cortical output in stroke patients.
AB  - BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been employed
      in following up a population of 20 stroke patients in a post-acute, apparently
      stabilized stage. Neurophysiological and clinical data were recorded in 5
      different recording sessions, from the beginning of a neuro-rehabilitation
      treatment (T0, at about 5 weeks from the ictal event.), followed up for about 4
      months (T4), with the purpose to study any modification of the cortical motor
      output in the course of a neuro-rehabilitation treatment. METHODS: Motor evoked
      potentials (MEPs) were simultaneously recorded from 10 muscles of both upper
      limbs (affected and not-affected); meanwhile, clinical and functional scores were
      gathered. Spinal responsiveness was investigated via H-reflex and F-wave
      recordings. RESULTS: We describe a pattern of improving changes still taking
      place four months after the stroke, even if the maximal amelioration burden was
      concentrated between T0 and T1 and T1 and T2 recording sessions (T0/admission to
      T2/42 days from T0=about 80 days from stroke occurrence). In particular, the
      excitability threshold (ETh) was progressively decreasing in the affected
      hemisphere (AH; P<0.001 between T0 and T4), while MEPs amplitude and latency
      tended toward normality, more in the resting state than during voluntary
      contraction. Slopes of neurophysiological and clinical data evolution were taken
      and trends of amelioration described. CONCLUSIONS: These findings suggest that
      rearrangements of motor cortical neural circuitries are still operating after
      several months from an acute vascular monohemispheric insult, coupled with a
      clinical improvement in disability and neurological scores. The steepest part of
      the slopes were evident in the first 80 days, suggesting that this period is the
      one in which plastic changes of cortical motor areas are mainly active.

PMID- 10964085
TI  - Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Aberdeen
      Colorectal Initiative.
AB  - Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular
      localization of which is often altered in human tumor cells. A common A/G single
      nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is
      associated with the presence of 2 distinct mRNA transcripts for this G1/S
      regulatory protein, and CCND1 genotype has been related to prognosis in lung
      cancer and head and neck carcinoma. We have investigated both the expression of
      cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer
      patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55%
      of tumors, and while the absence of cyclin D1 protein was not associated with
      outcome (p=0.81), high levels of protein expression (>50% of tumor cells
      expressing cyclin D1) correlated with significantly shortened overall survival
      (p=0.01). Using polymerase chain reaction restriction fragment length
      polymorphism analysis, we determined the frequency of each genotype and found
      that CCND1 genotype was not related to overall survival (p>0.05). In addition,
      genotype was unrelated to the level of expression and localization of cyclin D1
      protein, as well as other key G1/S checkpoint proteins (p21, p27, p53,
      retinoblastoma) and tumor proliferation markers (proliferating cell nuclear
      antigen). However, higher levels of p27, and to a lesser extent p21, were
      associated with reduced cytoplasmic cyclin D1 protein (p=0.029 and p=0.054,
      respectively). In conclusion, we have demonstrated that high levels of cyclin D1
      protein expression are related to outcome in colorectal cancer; however, the
      CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or
      patient survival.

PMID- 10964086
TI  - Online head motion tracking applied to the patient registration problem.
AB  - Image-guided systems for surgical procedures in the region of the head require a
      method to correlate the diagnostic image data with the corresponding site of
      pathology in the patient. Considering that patient movement can occur, detection
      and correction of such movement errors during the acquisition of images is a
      basic prerequisite for accurate treatment. For this reason, we developed a new
      registration method based upon on-line tracking of the patient's head to solve
      the problem of registration in the presence of head motion. The method provides
      non-invasive active patient registration for correction of movements during
      imaging and continuous update of the patient's head position during surgery. The
      patient motion correction applies the rigid body model to register the images
      using feature correspondence. The new registration method is described, and
      results of experiments that were performed to evaluate its accuracy and
      reliability in a plastic skull model and in patients are presented. The error
      analysis resulted in a final target registration error of 0.90 mm +/- 0.16 mm
      using experimental model data and 1.58 mm +/- 0.26 mm using clinical patient
      data. In addition, the residual registration error is modeled as a function of
      the measured and predicted head motion in order to determine the error that is
      introduced by motion tracking during image data acquisition. Furthermore, the
      clinical application of the method is demonstrated for oto-, rhino-, and
      neurosurgical procedures in the region of the head.

PMID- 10964087
TI  - A simulator for maxillofacial surgery integrating 3D cephalometry and
      orthodontia.
AB  - OBJECTIVES: This paper presents a new simulator for maxillofacial surgery that
      gathers the dental and maxillofacial analyses together into a single computer
      assisted procedure. The idea is to first propose a repositioning of the maxilla
      via the introduction of 3D cephalometry applied to a 3D virtual model of the
      patient's skull. Orthodontic data are then integrated into this model, using
      optical measurements of plaster casts of the teeth. MATERIALS AND METHODS: The
      feasibility of the maxillofacial demonstrator was first evaluated on a dry skull.
      To simulate malformations (and thus simulate a "real" patient), the skull was
      modified and manually cut by the surgeon to generate a given maxillofacial
      malformation (with asymmetries in the sagittal, frontal, and axial planes).
      RESULTS: The validation of our simulator consisted of evaluating its ability to
      propose a bone repositioning diagnosis that would restore the skull to its
      original configuration. An initial qualitative validation is provided in this
      paper, with a 1.5-mm error in the repositioning diagnosis. CONCLUSIONS: These
      results mainly validate the concept of a maxillofacial numerical simulator that
      integrates 3D cephalometry and guarantees a correct dental occlusion.

PMID- 10964088
TI  - An image-based 3D planning environment for hemicricolaryngectomy and
      reconstruction by tracheal autotransplantation.
AB  - OBJECTIVE: A new conservation method for unilateral glottal cancer with
      significant subglottal extension consists of a hemicricolaryngectomy and
      subsequent reconstruction of the laryngeal defect with a transferable patch of
      revascularized cervical trachea. In order to restore the three crucial functions
      of the larynx - airway patency, speech, and swallowing--the reconstructed larynx
      should resemble a situation with one paralyzed and one intact vocal fold at the
      glottal level. We hypothesize that this result can be achieved when the tracheal
      patch meets a typical surgical constraint--the so-called paramedian position at
      the glottal level - and when the patch is rigidly applied. This hypothesis was
      tested by developing and using an image-based planning system in a number of
      situations. MATERIALS AND METHODS: An image-based surgery simulator was developed
      according to the working hypothesis. To validate the transfer from planning
      towards actual surgery, a cadaver study was set up. Based on a patient case
      study, the sufficiency of the hypothesis for obtaining good functional results
      was evaluated. Finally, post-operative images of patients who were doing well
      after being operated without pre-operative planning were compared with
      retrospective planning to check the necessity of the hypothesis in obtaining good
      functionality of the neolarynx. RESULTS: We were able to design an efficient
      surgery simulator. The transfer from planning towards actual surgery is accurate,
      and satisfactory functional results were obtained from the patient case-study.
      The results from the retrospective planning showed that the hypothesis is not
      necessary to obtain good functional results, and that the smallest possible
      resection is preferred from the oncological point of view. CONCLUSION: The
      working hypothesis is sufficient for good functional results, but is unnecessary
      and often undesirable from an oncological point of view. Important lessons are
      drawn concerning our long-term goal of pre-operative determination of the shape
      and position of a tracheal patch suitable for optimizing the (neo-) laryngeal
      functions.

PMID- 10964089
TI  - Rhinosurgical therapy planning via endonasal airflow simulation.
AB  - Nowadays, Computational Fluid Dynamics (CFD) methods play an important part in
      the production process of the automotive industry. Progress in recent years has
      made possible highly sophisticated airflow-simulation models that are used in
      engineering for optimization and verification of aerodynamics. The key purpose of
      the Simulation Tool for Airflow in the human Nose (STAN), developed at the
      Darmstadt University of Technology in cooperation with the University Hospital in
      Greifswald, is to use these techniques to support the rhinosurgeon in diagnosis
      and planning of therapy (Fruhauf T, Mlynski G. Simulation and visualization of
      the air flow in the human nose. Proceedings of the First World Congress on
      Computational Medicine, Austin, Texas, 1994). A system has been developed that
      realizes a three-dimensional (3D) reconstruction of the endonasal cavities based
      on computer tomography (CT) scans. This semiautomatic reconstruction method
      requires minimal manual intervention. The surface model is used to create an
      unstructured 3D volume mesh suitable for finite volume simulations. In this way,
      an individual simulation based on patient-specific data can be realized. At the
      University Hospital in Greifswald, experimental investigations and measurements
      are made in nasal models to verify the simulation result. The goal of this
      project is to investigate individual nasal complaints and to detect respiratory
      disorders. The surgeon should be able to simulate the disordered respiration
      before performing a surgical procedure, and thereby increase the effectiveness of
      surgical planning.

PMID- 10964091
TI  - Announcements

PMID- 10964090
TI  - Final report of the technical requirements for image-guided spine procedures
      Workshop, April 17-20, 1999, Ellicott City, Maryland, USA.

PMID- 10964092
TI  - Announcements

PMID- 10964093
TI  - Defective nuclear localization of p53 protein in a Chinese hamster cell line is
      associated with the formation of stable cytoplasmic protein multimers in cells
      with gene amplification.
AB  - Many p53 functions require p53 transport into the nucleus. Mutant p53 also
      generally accumulates in the nucleus of transformed or neoplastic cells. However,
      examples of cytoplasmic accumulation of wild-type or mutant p53 have also been
      reported. Various explanations have been provided for defective nuclear
      localization. Here we propose a novel example of cytoplasmic p53 localization
      which occurs in cells showing gene amplification and appears to be due to the
      formation of stable p53 multimers. We studied a methotrexate-resistant Chinese
      hamster cell line (MTX M) carrying amplified dihydrofolate reductase genes and
      derived from a cell line with p53 nuclear accumulation. MTX M showed cytoplasmic
      p53 localization and, on immunoblots, several extra bands in the high molecular
      weight region, besides the expected 53 kDa band. p53 localization and the
      appearance of high molecular weight bands appeared to be correlated with the
      degree of DNA amplification. However, amplification of dihydrofolate reductase
      itself was not involved. Changing the p53 phosphorylation status quantitatively
      influenced the formation of high molecular weight bands. Cell fusion experiments
      demonstrated that p53 cytoplasmic localization in MTX M is a dominant phenotype.
      This result suggests that the defect causing lack of nuclear localization in this
      cell line does not reside in the nucleus. In the cytoplasm of MTX M and of wild
      type/MTX M heterodikaryons p53 gives rise to protein complexes that are unable to
      re-enter the nucleus. The formation of such protein complexes is dependent on the
      amplification of an unknown gene product.

PMID- 10964094
TI  - Mismatch repair is required for O(6)-methylguanine-induced homologous
      recombination in human fibroblasts.
AB  - O:(6)-methylguanine is responsible for homologous recombination induced by N:
      methyl-N:'-nitro-N:-nitrosoguanidine (MNNG) [H. Zhang et al. (1996)
      CARCINOGENESIS:, 17, 2229]. To test the hypothesis that mismatch repair is
      causally involved in this process, we generated mismatch repair-deficient strains
      from a human fibroblast line containing a substrate for detecting
      intrachromosomal homologous recombination. The four strains selected for study
      exhibited greatly increased resistance to the cytotoxic effects of MNNG, which
      was not affected by depletion of O:(6)-alkylguanine-DNA alkyltransferase, and
      greatly increased sensitivity to the mutagenic effect of MNNG, suggesting that
      the mutagenic base modifications induced in these four cell strains by MNNG
      persist in their genomic DNA. Tests showed that their extracts are deficient in
      the repair of G:T mismatches. The frequency of homologous recombination induced
      by MNNG in three of these strains was significantly (5-7-fold) lower than that
      induced in the parental cell strain. This was not the result of a generalized
      defect in recombination, because when (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha
      epox y-7,8,9, 10-tetrahydrobenzo[a]pyrene was used to induce recombination, all
      three lines responded with a normal or even a somewhat higher frequency than that
      observed in the parental strain. The lack of recombination displayed by the
      fourth strain was shown to result from the loss of part of the recombination
      substrate. The results strongly suggest that functional mismatch repair is
      required for MNNG-induced homologous recombination.

PMID- 10964095
TI  - Sustained angiogenesis enables in vivo transplantation of mucocutaneous derived
      AIDS-related Kaposi's sarcoma cells in murine hosts.
AB  - AIDS-related Kaposi's sarcoma (AIDS-KS), the most prevalent HIV-associated
      malignancy, is a debilitating, potentially fatal disease. Currently, there is a
      need for development of AIDS-KS therapies that are not only well tolerated, but
      also capable of providing sustained remission. Preclinical assessment of
      pharmacological parameters and therapeutic efficacies are dependent upon in vivo
      parameters. However, there are currently no animal KS models and mucocutaneous KS
      cell isolates have proved to be non-tumorigenic in animal hosts. This report
      describes the development of a murine model that enables in vivo transplantation
      of 'native' low population doubling level AIDS-KS cells from biopsy-confirmed
      mucocutaneous lesions. The angiogenic phenotype of in situ AIDS-KS lesions is
      reconstituted via controlled release of a complete angiogenic peptide,
      recombinant human basic fibroblast growth factor (bFGF), from locally injectable,
      biodegradable polylactide-co-glycolide implants. Consequential to the sustained
      local release of bioactive bFGF, a murine vascular network is established, which
      facilitates the in vivo transplantation of AIDS-KS cells. Desirable aspects of
      this model include: low cost murine species, transplantation of non-selected
      patient cells and use of animal hosts that are T cell-deficient. The transplanted
      human AIDS-KS cells and extensive murine vascular network create lesions that
      retain a striking resemblance, at both the gross and microscopic levels, to in
      situ AIDS-KS tumors. Because the bFGF-induced murine vascular network is
      analogous to the abundant vascularity present in AIDS-KS lesions, this murine
      model should provide an excellent vehicle for numerous clinically relevant
      studies, such as assessment of drug clearance at AIDS-KS lesional sites. Finally,
      applicability of this method is not restricted to AIDS-related malignancies.
      Establishment and maintenance of an extensive host vascular network should
      augment success rates for in vivo transplantation of numerous other human cell
      strains or lines.

PMID- 10964096
TI  - Chemoprevention studies of the flavonoids quercetin and rutin in normal and
      azoxymethane-treated mouse colon.
AB  - In this study we investigated the chemopreventive effects of quercetin and rutin
      when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)
      treated mice. Early changes in colonic mucosa were analyzed, including colonic
      cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas
      of dysplasia (FAD). The findings show that the number of colonic epithelial cells
      per crypt column increased (P: < 0.01) in each normal mouse group fed the
      flavonoids; AOM administration increased colonic crypt cell proliferation and
      resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower
      proliferative zone of the crypt. Both supplementary dietary quercetin and rutin
      increased the apoptotic index and caused a redistribution of apoptotic cells
      along the crypt axis in normal mice fed a standard AIN-76A diet. The number of
      apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in
      the AOM-treated group compared with untreated animals; apoptotic cells expanded
      throughout the colonic crypts after flavonoid supplementation and AOM
      administration. Positive cyclin D(1) expression was detected in mice on diets
      supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM
      administration resulted in the formation of FAD. Both the number of mice
      exhibiting FAD and the total numer of FAD observed were significantly reduced (P:
      < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on
      the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to
      induce FAD in 22% of normal mice fed the standard AIN-76A diet.

PMID- 10964097
TI  - Biomarkers of exposure and effect as indicators of potential carcinogenic risk
      arising from in vivo metabolism of ethylene to ethylene oxide.
AB  - The purposes of the present study were: (i) to investigate the potential use of
      several biomarkers as quantitative indicators of the in vivo conversion of
      ethylene (ET) to ethylene oxide (EO); (ii) to produce molecular dosimetry data
      that might improve assessment of human risk from exogenous ET exposures. Groups
      (n = 7/group) of male F344 rats and B6C3F1 mice were exposed by inhalation to 0
      and 3000 p. p.m. ET for 1, 2 or 4 weeks (6 h/day, 5 days/week) or to 0, 40, 1000
      and 3000 p.p.m. ET for 4 weeks. N:-(2-hydroxyethyl)valine (HEV), N:7-(2
      hydroxyethyl) guanine (N7-HEG) and HPRT: mutant frequencies were assessed as
      potential biomarkers for determining the molecular dose of EO resulting from
      exogenous ET exposures of rats and mice, compared with background biomarker
      values. N7-HEG was quantified by gas chromatography coupled with high resolution
      mass spectrometry (GC-HRMS), HEV was determined by Edman degradation and GC-HRMS
      and HPRT: mutant frequencies were measured by the T cell cloning assay. N7-HEG
      accumulated in DNA with repeated exposure of rodents to 3000 p.p.m. ET, reaching
      steady-state concentrations around 1 week of exposure in most tissues evaluated
      (brain, liver, lung and spleen). The dose-response curves for N7-HEG and HEV were
      supralinear in exposed rats and mice, indicating that metabolic activation of ET
      was saturated at exposures >/=1000 p.p.m. ET. Exposures of mice and rats to 200
      p.p.m. EO for 4 weeks (as positive treatment controls) led to significant
      increases in HPRT: mutant frequencies over background in splenic T cells from
      exposed rats and mice, however, no significant mutagenic response was observed in
      the HPRT: gene of ET-exposed animals. Comparisons between the biomarker data for
      both unexposed and ET-exposed animals, the dose-response curves for the same
      biomarkers in EO-exposed rats and mice and the results of the rodent
      carcinogenicity studies of ET and EO suggest that too little EO arises from
      exogenous ET exposure to produce a significant mutagenic response or a
      carcinogenic response under standard bioassay conditions.

PMID- 10964098
TI  - Prevention of the down-regulation of gap junctional intercellular communication
      by green tea in the liver of mice fed pentachlorophenol.
AB  - Much evidence has been documented supporting the hypothesis that the down
      regulation of gap junctional intercellular communication (GJIC) is a cellular
      event underlying the tumor promotion process and that treatment to prevent the
      down-regulation or to up-regulate GJIC is important in preventing tumor
      promotion. We explored the potential preventive effects of green tea against the
      promoting action of pentachlorophenol (PCP) in mouse hepatocarcinogenesis,
      examining whether drinking green tea prevents the down-regulation of GJIC
      inhibition in the liver caused by tumorigenic doses of PCP. We used a modified in
      vivo GJIC assay, the incision loading/dye transfer method. Male B6C3F1 mice were
      given a green tea infusion for 1 week and then PCP was fed at a dose of 300 or
      600 p.p.m. in the diet for the following 2 weeks, along with green tea treatment.
      A dose-related inhibition of GJIC in the hepatocytes was evident in the mice
      treated with PCP alone that was associated with a reduction in connexin32 (Cx32)
      plaques in the plasma membrane and an increase in the cell proliferation index.
      Drinking green tea significantly protected mice against GJIC inhibition, the
      reduction in Cx32 and the elevation of the labeling index. These findings suggest
      that green tea might act as an anti-promoter against PCP-induced mouse
      hepatocarcinogenesis via its ability to prevent down-regulation of GJIC.

PMID- 10964099
TI  - Less than additive interaction between cigarette smoke and chromium(VI) in
      inducing clastogenic damage in rodents.
AB  - A combination of tobacco smoking with certain agents has been shown to exert
      synergistic carcinogenic effects. On the other hand, antagonism betweeen smoke
      and other pulmonary carcinogens has also been documented by both epidemiological
      and experimental data. In spite of a very large number of studies carried out for
      decades in workers exposed to hexavalent chromium, the influence of smoking
      habits on lung carcinogenesis induced by this metal has not been clarified. For
      this reason, we performed two studies evaluating clastogenic effects in rodents.
      In the first one, BDF(1) mice were exposed whole-body to mainstream cigarette
      smoke for 5 days and, on the last day, they received an i.p. injection of
      potassium dichromate. In the second study, Sprague-Dawley rats were exposed whole
      body to environmental cigarette smoke for 18 consecutive days and for the same
      period of time they received daily intra-tracheal instillations of sodium
      dichromate. Individually, the two hexavalent chromium salts and cigarette smoke,
      either mainstream or environmental, enhanced the frequency of micronuclei in bone
      marrow polychromatic erythrocytes of both mice and rats. Moreover, individual
      exposure to either environmental cigarette smoke or sodium dichromate enhanced
      the frequency of micronuclei and multiple nuclei in pulmonary alveolar
      macrophages of rats. In both studies, combined exposure to cigarette smoke and
      hexavalent chromium produced less than additive clastogenic effects. These
      results are consistent with our previous data, showing that hexavalent chromium
      and either benzo[a]pyrene or cigarette smoke condensate behave antagonistically
      in in vitro mutagenicity test systems and that the chromium reducing capacity of
      human pulmonary alveolar macrophages and peripheral lung parenchyma is enhanced
      in smokers. Taken together, in the absence of any epidemiological evidence, these
      findings rule out any occurrence of synergism between cigarette smoke and
      hexavalent chromium, at least in certain stages of the carcinogenesis process.

PMID- 10964100
TI  - Metabolic activation of carcinogens and expression of various cytochromes P450 in
      human prostate tissue.
AB  - Epidemiological evidence suggests a link between meat consumption and prostate
      cancer. In this study, benign prostatic hyperplasia tissues, obtained by
      transurethral resection or radical retropubic prostatectomy from UK-resident
      individuals (n = 18), were examined for CYP1 expression and for their ability, in
      short-term organ culture, to metabolically activate carcinogens found in cooked
      meat. Semi-quantitative RT-PCR analysis of CYP1 expression detected CYP1A2 mRNA
      transcripts in the prostates of four individuals, as well as mRNA transcripts
      from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2
      amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP; 500 microM, n = 9) and its
      metabolite N:-hydroxy PhIP (20 microM, n = 8), 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ; 500 microM, n = 6) and benzo[a]pyrene (B[a]P; 50 microM, n = 5).
      After incubation (PFMR medium, 22 h, 37 degrees C), DNA was isolated from tissue
      fragments and DNA adducts were detected and quantified by (32)P-postlabelling
      analysis. DNA adduct formation was detected in all samples incubated with PhIP
      (mean, adducts per 10(8) nucleotides), N:-hydroxy-PhIP (2736/10(8)) or B[a]P
      (1/10(8)). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/10(8)). The CYP1
      inhibitor alpha-naphthoflavone (10 microM) reduced B[a]P-DNA adduct formation in
      tissues from two individuals by 96 and 64%, respectively. This pilot study shows
      that human prostate tissue can metabolically activate 'cooked meat' carcinogens,
      a process that could contribute to prostate cancer development.

PMID- 10964101
TI  - Hypermethylation of the p16 (Ink4a) promoter in B6C3F1 mouse primary lung
      adenocarcinomas and mouse lung cell lines.
AB  - Primary lung tumors from B6C3F1 mice and mouse lung cell lines were examined to
      investigate the role of transcriptional silencing of the p16 (Ink4a) tumor
      suppressor gene by DNA hypermethylation during mouse lung carcinogenesis.
      Hypermethylation (>/=50% methylation at two or more of the CpG sites examined) of
      the p16 (Ink4a) promoter region was detected in DNA from 12 of 17 (70%) of the
      B6C3F1 primary mouse lung adenocarcinomas examined, whereas hypermethylation was
      not detected in normal B6C3F1, C57BL/6 and C3H/He mouse lung tissues.
      Immunohistochemistry performed on the B6C3F1 lung adenocarcinomas revealed
      heterogeneous expression of the p16 protein within and among the tumors. Laser
      capture microdissection was employed to collect cells from immunostained sections
      of four tumors displaying areas of relatively high and low p16 expression. The
      methylation status of the microdissected samples was assessed by sodium bisulfite
      genomic sequencing. The pattern of p16 expression correlated inversely with the
      DNA methylation pattern at promoter CpG sites in nine of 11 (82%) of the
      microdissected areas displaying variable p16 expression. To provide further
      evidence that hypermethylation is involved in the loss of p16 (Ink4a) gene
      expression, three mouse lung tumor cell lines (C10, sp6c and CMT64) displaying
      complete methylation at seven promoter CpG sites and no p16 (Ink4a) expression
      were treated with the demethylating agent, 5-aza-2'-deoxycytidine. Re-expression
      of p16 (Ink4a) and partial demethylation of the p16 (Ink4a) promoter were
      observed in two cell lines (C10 and sp6c) following treatment. These are the
      first reported studies to provide strong evidence that DNA methylation is a
      mechanism for p16 inactivation in mouse lung tumors.

PMID- 10964102
TI  - Molecular cloning and characterization of the human KIN17 cDNA encoding a
      component of the UVC response that is conserved among metazoans.
AB  - We describe the cloning and characterization of the human KIN17 cDNA encoding a
      45 kDa zinc finger nuclear protein. Previous reports indicated that mouse kin17
      protein may play a role in illegitimate recombination and in gene regulation.
      Furthermore, overproduction of mouse kin17 protein inhibits the growth of
      mammalian cells, particularly the proliferation of human tumour-derived cells. We
      show here that the KIN17 gene is remarkably conserved during evolution. Indeed,
      the human and mouse kin17 proteins are 92.4% identical. Furthermore, DNA
      sequences from fruit fly and filaria code for proteins that are 60% identical to
      the mammalian kin17 proteins, indicating conservation of the KIN17 gene among
      metazoans. The human KIN17 gene, named (HSA)KIN17, is located on human chromosome
      10 at p15-p14. The (HSA)KIN17 RNA is ubiquitously expressed in all the tissues
      and organs examined, although muscle, heart and testis display the highest
      levels. UVC irradiation of quiescent human primary fibroblasts increases
      (HSA)KIN17 RNA with kinetics similar to those observed in mouse cells, suggesting
      that up-regulation of the (HSA)KIN17 gene after UVC irradiation is a conserved
      response in mammalian cells. (HSA)kin17 protein is concentrated in intranuclear
      focal structures in proliferating cells as judged by indirect immunofluorescence.
      UVC irradiation disassembles (HSA)kin17 foci in cycling cells, indicating a link
      between the intranuclear distribution of (HSA)kin17 protein and the DNA damage
      response.

PMID- 10964103
TI  - Effects of benzyl isothiocyanate and phenethyl isothiocyanate on benzo[a]pyrene
      metabolism and DNA adduct formation in the A/J mouse.
AB  - Benzyl isothiocyanate (BITC) inhibits lung tumorigenesis induced in A/J mice by
      benzo[a]pyrene (B[a]P). In contrast, phenethyl isothiocyanate (PEITC) does not.
      We tested the hypothesis that BITC inhibits B[a]P tumorigenicity in mouse lung by
      inhibiting DNA adduct formation, and compared the effects of BITC and PEITC. In
      mouse liver or lung microsomal incubations, BITC and PEITC inhibited formation of
      7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (B[a]P-7, 8-diol) and some other B[a]P
      metabolites. The metabolism of B[a]P was compared in mouse lung and liver
      microsomes, 6 or 24h after treatment with BITC or PEITC. In lung, 6 h after
      treatment, B[a]P-7, 8-diol and some other metabolites were inhibited by BITC and
      PEITC. However, 24 h after treatment, no inhibition of B[a]P-7,8-diol was
      observed in microsomes from BITC-treated mice, whereas it was substantially
      increased in mice treated with PEITC. Effects on B[a]P metabolism in liver
      microsomes were generally modest. Conversion of B[a]P-7,8-diol to mutagens by
      mouse liver microsomes was more strongly inhibited by BITC than PEITC. Effects on
      7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA adduct
      formation were evaluated in DNA from mice treated with isothiocyanates and B[a]P,
      and killed 2-120h later. The area under the curve (AUC) for BPDE-DNA adducts in
      lung was 29.5% less (P = 0. 001) in the BITC-B[a]P treated mice and 19.0% less (P
      = 0.02) in the PEITC-B[a]P mice than in the mice treated with B[a]P alone.
      Similar results were obtained in liver DNA. There were no significant differences
      between the reduction of BPDE-DNA AUC values by BITC versus PEITC. The results of
      this study support the hypothesis that BITC inhibits B[a]P-induced lung
      tumorigenesis in A/J mice by inhibiting the metabolic activation of B[a]P to BPDE
      DNA adducts. However, differences in BPDE-DNA adduct formation do not appear to
      explain fully the contrasting effects of BITC and PEITC on B[a]P-induced lung
      tumorigenesis.

PMID- 10964104
TI  - Comparison of genetic changes in schistosome-related transitional and squamous
      bladder cancers using comparative genomic hybridization.
AB  - The development of bladder tumors has been associated with a number of causative
      agents, including schistosomiasis. Schistosome-related cancers show different
      clinical and pathological features compared with non-schistosome-related bladder
      cancers, occurring in younger patients, and being predominantly of squamous cell
      type. This study addresses the difference between squamous and transitional tumor
      types in the presence of schistosome infection as a measure of the relationship
      between tumor genotype and phenotype. We have used comparative genomic
      hybridization to analyze primary muscleinvasive schistosome-related bladder
      tumors in 54 patients. Twenty-six of these tumors were squamous cell carcinomas;
      the remaining 28 were of transitional cell type. On average, transitional cell
      tumors showed 1.8 times the number of chromosomal aberrations as squamous cell
      tumors (14.4 versus 8.2, P: < 0.001). For both groups combined, the most
      prevalent genetic alterations were losses of 8p and 18q, and gains of 8q.
      Transitional cell cancers also showed frequent losses involving 5q, 9p, 10q, 11p
      and 11q, and gains at 1q and 17q. Loss of 11p was significantly more frequent in
      TCC than in SCC tumors (50 versus 4%, P: = 0.01). Squamous cell cancers showed
      more frequent losses of 17p and 18p than transitional tumors, which was clearly
      significant given the overall reduced frequency of changes in squamous cancers
      (P: = 0.001 and P: = 0.03, respectively). These data show that different
      histologic subgroups of bladder tumors are characterized by distinct patterns of
      chromosomal alterations. The genetic changes found in the transitional cell group
      are similar to those reported in non-schistosome-related transitional cell
      tumors, but differ from tumors exhibiting squamous differentiation.

PMID- 10964105
TI  - Sequence-dependent conformational perturbation in DNA duplexes containing an
      epsilonA.T mismatch using molecular dynamics simulation.
AB  - Previous experiments from this laboratory showed that 1, N:(6)-ethenoadenine
      (epsilonA) in 15mer DNA oligonucleotide duplexes with GGepsilonAGG and
      CCepsilonACC central sequences is repaired 3-5-fold more efficiently than in
      duplexes containing AAepsilonAAA and TTepsilonATT central sequences. This
      sequence dependence in repair rates appeared to correlate with the observed
      thermodynamic stability of these duplexes [Hang et al. (1998) J. Biol. Chem.,
      273, 33406-33413]. In the present work, unrestrained molecular dynamics was used
      to evaluate the sequence-dependent structural features of these duplexes.
      Explicit solvent and the particle mesh Ewald method were applied for the accurate
      representation of the electrostatic interactions. The differences observed in the
      axis- and intra-base pair parameters were primarily localized at the epsilonA*T
      mismatch in all sequences and indicate conformational diversity between the
      structures. However, all four structures remained in the B-conformational family.
      In the tip, tilt and propeller twist parameters for the five central base pairs,
      larger perturbations were found for the two duplexes with epsilonA flanked by A
      or T bases than for duplexes with epsilonA flanked by G or C bases. As a result
      of these perturbations, the average global curvature of the AAepsilonAAA and
      TTvarepsilonATT DNA duplexes was larger by approximately 12 degrees than that of
      the duplexes with the GGepsilonAGG and CCepsilonACC central sequences. The
      observed conformational differences between the duplexes containing A or T and G
      or C neighbors of epsilonA may contribute to the observed differential enzymatic
      repair of the same sequences.

PMID- 10964106
TI  - Identification of hepatic tamoxifen-DNA adducts in mice: alpha-(N(2)
      deoxyguanosinyl)tamoxifen and alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide.
AB  - Tamoxifen-DNA adducts detected in the liver of mice treated with tamoxifen have
      not yet been identified. In the present study a new type of tamoxifen-DNA adduct,
      four stereoisomers of alpha-(N:(2)-deoxyguanosinyl)tamoxifen N:-oxide 3'
      monophosphate (dG(3'P)-N:(2)-TAM N:-oxide) were prepared as standard DNA adducts
      by reacting 2'-deoxyguanosine 3'-monophosphate with trans-alpha-acetoxytamoxifen
      N:-oxide in addition to four stereoisomers of alpha-(N:(2)-deoxyguano-
      sinyl)tamoxifen 3'-monophosphate (dG(3'P)-N:(2)-TAM) that was reported
      previously. Liquid chromatography-electrospray ionization-mass spectrometry of
      the reaction products gave the most abundant ion at m/z 731 ([M - H](-)), which
      corresponded to dG(3'P)-N:(2)-TAM N:-oxide. The modified products digested by
      alkaline phosphatase corresponded to the isomers of dG-N:(2)-TAM N:-oxide whose
      structures were identified previously by mass spectrometry and nuclear magnetic
      resonance. Using these standard markers, we analyzed the hepatic DNA adducts of
      female DBA/2 mice treated with tamoxifen at a dosage of 120 mg/kg/day for 7 days
      by (32)P-post-labeling coupled with an HPLC/radioactive detector. Mixtures of
      eight isomers of dG(3'P)-N:(2)-TAM and dG(3'P)-N:(2)-TAM N-oxide were separated
      into six peaks, since each of the cis epimers were not separated under the
      present HPLC conditions. Nine adducts were detected in all liver samples of mice.
      An epimer of trans-dG(3'P)-N:(2)-TAM was detected as the principal DNA adduct at
      a level of 29.0 adducts/10(8) nucleotides, which accounted for 53.3% of the total
      tamoxifen-DNA adducts. Lesser amounts of cis-dG(3'P)-N:(2)-TAM (2.8%) were also
      observed. An epimer of the trans-dG(3'P)-N:(2)-TAM N:-oxide (3.9 adducts/10(8)
      nucleotides) was detected as the third biggest adduct (7.2% of the total). The
      cis-dG(3'P)-N:(2)-TAM N:-oxide (0.4 adducts/10(8) nucleotides) accounted for 0.7%
      of the total. Thus, dG(3'P)-N:(2)-TAM and dG(3'P)-N:(2)-TAM N:-oxide were
      identified in tamoxifen-treated mouse liver.

PMID- 10964107
TI  - The induction of cyclooxygenase-1 by a tobacco carcinogen in U937 human
      macrophages is correlated to the activation of NF-kappaB.
AB  - The nicotine-derived 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK),
      present in tobacco smoke, is most likely involved in lung carcinogenesis in
      smokers. We demonstrated previously that non-steroidal anti-inflammatory drugs
      (NSAIDs) inhibit NNK-induced lung tumorigenesis, although the mechanism(s) is
      unknown. The present study demonstrates that, in U937 human macrophages,
      cyclooxygenase (COX)-1 and -2 are involved in the bioactivation of NNK to
      electrophilic mutagenic intermediates. We observed that acetylsalicylic acid and
      NS-398 decrease COX-dependent NNK activation in U937 cells by 66 and 37%,
      respectively. NSAIDs also decrease prostaglandin E(2) (PGE(2)) synthesis, which
      is induced in a dose-dependent manner, reaching a 7-fold increase, in NNK-treated
      human U937 cells. We observed that NNK induces COX-1 expression and activates the
      nuclear factor-kappaB (NF-kappaB), in U937 cells. N:-acetyl-L-cysteine and
      pyrrolidinedithiocarbamate, two inhibitors of reactive oxygen species (ROS),
      inhibit NNK-induced PGE2 synthesis by 41 and 44%, respectively. These data
      suggest that ROS, generated during pulmonary metabolism of NNK could act as
      signal transduction messengers and activate NF-kappaB, which will subsequently
      induce COX-1 activity and increase PGE(2) synthesis. These results reveal a novel
      aspect of tobacco carcinogenesis, and give us insight into the mechanisms of
      chemoprevention by NSAIDs. Accordingly, inhibition of NF-kappaB activation,
      leading to the inhibition of COX, offers a new approach in lung cancer
      prevention.

PMID- 10964108
TI  - Detection of somatic DNA alterations in azoxymethane-induced F344 rat colon
      tumors by random amplified polymorphic DNA analysis.
AB  - Colon carcinogenesis induced in rats by azoxymethane (AOM) is a useful
      experimental model as it mimics the human adenoma-carcinoma sequence and allows
      the study of dietary variation and of the effects of chemopreventive substances.
      Alterations of specific oncogenes and tumor suppressor genes (APC and K-ras) play
      roles at different stages of this carcinogenesis process. Recently, it has been
      suggested that genomic instability is the necessary step for the generation of
      multiple mutations underlying the occurrence of cancer. We studied the frequency
      of K-ras and microsatellite instability (MSI) in 30 colorectal tumors induced by
      AOM (30 mg/kg) in F344 rats. We also used the random amplified polymorphic DNA
      (RAPD) method to identify genomic alterations in chemically induced aberrant
      crypt foci (ACF), adenomas and adenocarcinomas. K-ras mutations were identified
      in 16.7% of the cases (5/30; 9% in adenomas and 37.5% in adenocarcinomas) and MSI
      in 20% (6/30) of the tumors (only one sample exhibited instability at more than
      one locus). Of 21 primers used for the RAPD assay, six were very informative. All
      the analyzed tumors (16/16) showed at least one RAPD profile with lost or
      additional bands compared with the normal mucosa. A lower level of genomic
      alteration was present in the ACF analyzed (7/10). In conclusion, K-ras and MSI
      are not often involved in the AOM carcinogenesis in the rat, whereas extensive
      genomic instability is always present and can be detected using the RAPD
      analysis.

PMID- 10964109
TI  - A dominant negative form of IKK2 prevents suppression of apoptosis by the
      peroxisome proliferator nafenopin.
AB  - Peroxisome proliferators (PPs) are a class of non-genotoxic chemicals that cause
      rodent liver enlargement and hepatocarcinogenesis. In primary rat hepatocyte
      cultures, PPs suppress spontaneous apoptosis and that induced by a number of pro
      apoptotic stimuli such as transforming growth factor-beta(1). Tumour necrosis
      factor alpha (TNF-alpha) and the transcription factor NFkappaB have been
      implicated in the mode of action of PPs. TNF-alpha signalling to NFkappaB is
      thought to be responsible for many of the effects elicited by this cytokine.
      NFkappaB regulates gene expression in immunity, stress responses and the
      inhibition of apoptosis. Activation of NFkappaB requires the successive action of
      NFkappaB-inducing kinase and the phosphorylation of NFkappaB inhibitory proteins
      (IkappaB) by an IkappaB kinase (IKK) complex. The IKK2 subunit of IkappaB kinase
      is thought to be essential for NFkappaB activation and prevention of apoptosis.
      To determine whether IKK2 plays a role in the suppression of apoptosis by PPs, we
      expressed a dominant negative form of IKK2 (IKK2dn) in primary rat hepatocyte
      cultures. Infection with an adenovirus construct expressing IKK2dn caused
      apoptosis in control primary rat hepatocytes in the absence of exogenous TNF
      alpha. Moreover, IKK2dn-induced apoptosis could not be rescued by addition of TNF
      alpha or the peroxisome proliferator nafenopin. These results demonstrate a
      requirement for intracellular signalling pathways mediated by IKK2 in the
      suppression of apoptosis by the PP class of hepatocarcinogens.

PMID- 10964111
TI  - Phorbol ester-induced production of cytostatic factors by normal and oncogenic Ha
      ras-transformed human breast cell lines carcinogenesis, 21, 1303-1308 (2000)

PMID- 10964110
TI  - Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels
      in clinical breast cancer specimens.
AB  - Functional inactivation of BRCA1 is an important mechanism involved in breast
      cancer pathogenesis. Mutation is often responsible for BRCA1 inactivation in
      familial breast cancer, but is not responsible for the decreased levels of BRCA1
      seen in a subset of sporadic breast cancer patients. To determine if aberrant
      cytosine methylation of the BRCA1 promoter is associated with decreased BRCA1
      gene expression in human breast cancer, high resolution bisulfite sequence
      analysis was used to analyze the cytosine methylation status of the BRCA1
      promoter in 21 axillary node negative breast cancer patients with known levels of
      BRCA1 expression. Aberrant cytosine methylation of the BRCA1 promoter was
      detected in three of 21 patient specimens. These three specimens also expressed
      the lowest levels of BRCA1. Results from this analysis show that aberrant
      cytosine methylation of the BRCA1 promoter is directly correlated with decreased
      levels of BRCA1 expression in human breast cancer, and suggest that epigenetic
      silencing may be one mechanism of transcriptional inactivation of BRCA1 in
      sporadic mammary carcinogenesis.

PMID- 10964112
TI  - Specialty secondments for accident and emergency registrars.

PMID- 10964113
TI  - Thyroid disorders--an update.

PMID- 10964114
TI  - Hearing impairment in older people: a review.

PMID- 10964115
TI  - Recent advances in ischaemic heart disease.
AB  - There continue to be important developments in the understanding of the
      pathogenesis of coronary artery disease. Advances have also been made in both the
      medical and interventional management of patients with ischaemic heart disease.
      This review has, however, not focused on the wider developments that have
      occurred in the area of percutaneous intervention. The vast array of new stent
      designs and other interventional devices have had a considerable impact on the
      treatment of obstructive coronary disease. In addition it is likely that further
      developments will be seen in areas such as intracoronary radiotherapy to reduce
      restenosis after PTCA and in gene therapy to promote angiogenesis in ischaemic
      myocardium. Both of which will be discussed in a future review of this area.

PMID- 10964116
TI  - Video assisted thoracoscopic surgery.

PMID- 10964117
TI  - Ophthalmology and general medicine.

PMID- 10964118
TI  - Images in medicine. Multifocal breast cancer.

PMID- 10964119
TI  - Difficulties in diagnosing and treating depression in the terminally ill cancer
      patient.
AB  - It is estimated that for a quarter of all patients with advanced metastatic
      cancer, depression will be significant symptom. However up to 80% of the
      psychological and psychiatric morbidity which develops in cancer patients goes
      unrecognised and untreated. One of the main difficulties in establishing a
      diagnosis of an illness where there are no biological markers, physical signs, or
      diagnostics tests is deciding what can be called "appropriate sadness" as
      patients approach the end of life and what is a depressive illness. Criteria for
      diagnosing depression are discussed together with reasons why established
      screening tools used in other populations may not be appropriate to screen for
      depression in terminally ill patients. The use of antidepressants and the role of
      cognitive therapies are also discussed. For effective treatment of a depressive
      illness, treatment with antidepressant medication needs to be initiated sooner
      rather than later and patients may need close supervision to ensure compliance.
      The awareness of depression, the identification of symptoms, and the initiation
      of treatment is essential if patients are to be offered optimum palliation of
      psychological as well as physical symptoms.

PMID- 10964120
TI  - Gradenigo's syndrome.
AB  - Gradenigo's syndrome, which is characterised by the triad of suppurative otitis
      media, pain in the distribution of the trigeminal nerve, and abducens nerve palsy
      may give rise to potentially fatal complications. Knowledge of the aetiology and
      appropriate investigations can lead to early diagnosis. A case is reported which
      illustrates this.

PMID- 10964122
TI  - Investigating lymphadenopathy--report on the first 12 months of the lymph node
      diagnostic clinic at the Royal Marsden Hospital.
AB  - The lymph node diagnostic clinic was set up at the Royal Marsden Hospital to
      provide a direct access service for general practitioners. In the first year 82
      patients were seen. The malignancy pick-up rate was 19.5% which compares very
      favourably to rates in breast and colorectal clinics. Patient and general
      practitioner satisfaction with the service was high.

PMID- 10964121
TI  - High prevalence of iliofemoral venous thrombosis with severe groin infection
      among injecting drug users in North East Scotland: successful use of low
      molecular weight heparin with antibiotics.
AB  - Injecting drug use, mainly of heroin, currently represents a major public health
      issue in the North East of Scotland. The recent tendency of the committed
      injecting drug user to inject into the groin has created novel problems for the
      Infection Unit. Data are presented on 20 consecutive patients admitted between
      1994 and 1999 with iliofemoral venous thromboses, often complicated by severe
      soft tissue infections and bacteraemia as a result of heroin injection into the
      femoral vein. Nine had coexistent groin abscesses, four had severe streptococcal
      soft tissue infection of the right thigh, groin and lower abdomen, and two had
      coincidental soft tissue infections of the upper limb. Nine were bacteraemic on
      admission. All of the patients were chronic injecting drug users with a median
      injection duration of 6.5 years. The 18 patients tested for hepatitis C virus
      were all seropositive. None of the 14 patients tested was positive for HIV.
      Seventeen patients were treated with subcutaneous low molecular weight heparin
      (tinzaparin), three having received intravenous unfractionated heparin initially.
      The tinzaparin was self administered and given for a median duration of seven
      weeks. One patient declined to have any treatment. Three months after
      presentation eight patients were asymptomatic, seven had a persistently swollen
      leg, and five were lost to follow up. None developed clinically apparent
      pulmonary embolism after institution of anticoagulant therapy. The management of
      iliofemoral venous thrombosis in injection drug users is problematic because of
      poor venous access, non-compliance with prescribed treatment, ongoing injecting
      behaviour, and coexistent sepsis. It is unlikely that a randomised trial of
      standard treatment with heparin and warfarin versus low molecular weight heparin
      alone would be practical in this patient group. These retrospective data indicate
      that the use of tinzaparin in injecting drug users is feasible and appears to
      result in satisfactory clinical responses. The possibility of concomitant
      infection in injecting drug users with venous thrombosis should always be
      addressed, as it appears to be a common phenomenon. Early drainage of abscesses
      and antimicrobial chemotherapy, often administered intramuscularly or orally
      because of lack of peripheral venous access, is central to the appropriate care
      of these patients.

PMID- 10964124
TI  - Indomethacin induced avascular necrosis of head of femur.
AB  - Chemically induced avascular necrosis of bone is a well documented entity.
      Indomethacin is one of the causes of this condition but is often difficult to
      recognise. Review of the literature shows that only one case of indomethacin
      induced avascular necrosis has been reported in the English language between 1966
      and the present. The case of a young healthy man, who developed avascular
      necrosis of head of femur after prolonged administration of indomethacin, is
      reported here.

PMID- 10964125
TI  - Base of tongue varices associated with portal hypertension.
AB  - A symptomatic case of tongue base varices in a patient with portal hypertension
      secondary to liver cirrhosis is presented. There are no previously documented
      cases in the world literature. Oesophageal varices may not be the only source of
      expectorated blood in a patient with portal hypertension.

PMID- 10964123
TI  - Frequency of proteinuria in type 2 diabetes mellitus seen at a diabetes centre in
      southern India.
AB  - The frequency of proteinuria was assessed in a cohort of 1848 diabetic patients
      attending a diabetes centre in south India. A total of 127 (6.9%) patients had
      evidence of macroproteinuria and 49 (2.5%) patients had microproteinuria. Thus
      overall 9.4% of patients had diabetes related proteinuria. In addition, 70
      patients (3.8%) had evidence of proteinuria with no evidence of retinopathy. The
      frequency of both microproteinuria and macroproteinuria increased linearly with
      duration of diabetes. Multiple logistic regression analysis showed that duration
      of diabetes, serum creatinine, and glycated haemoglobin were risk factors for
      macroproteinuria.

PMID- 10964126
TI  - Cefuroxime induced lymphomatoid hypersensitivity reaction.
AB  - An 84 year old woman developed erythematous blotchy erythema and purpuric rashes
      over the lower limbs three days after being started on intravenous cefuroxime for
      acute diverticulitis. A skin biopsy specimen showed a mixed infiltrate of
      lymphoid cells and eosinophils; many of the lymphocytes were large, pleomorphic,
      and showed a raised mitotic rate. Immunohistochemistry showed the infiltrate to
      be T cell rich, with all the large cells being CD30 positive. Typical mycosis
      fungoides cells, marked epidermotropism, and Pautrier's abscesses were not seen.
      The rash disappeared 10 days after cessation of cefuroxime and the patient
      remained asymptomatic 15 months later. This apparent cutaneous T cell lymphoma
      like reaction is best described as lymphomatoid vascular reaction. The drug
      induced immune response with an atypical cutaneous lymphoid infiltrate mimics a
      cutaneous pseudolymphoma.

PMID- 10964128
TI  - International herpes management forum (www.IHMF.org)

PMID- 10964127
TI  - Colonic carcinoma after ureterosigmoidostomy.
AB  - Urinary carcinogens promote late malignant transformation of the colon after a
      ureterosigmoidostomy. An unusual case is presented where, despite the early
      removal of the latter and hence cessation of urine flow, a colonic carcinoma
      developed at the site of previous anastomosis. The importance of surveillance of
      all patients who have undergone this procedure to avoid an iatrogenic cancer is
      emphasised.

PMID- 10964129
TI  - A pulmonary mass and hyperviscosity.

PMID- 10964130
TI  - Abdominal pain in a 22 year old woman.

PMID- 10964131
TI  - A rare cause of unilateral hearing loss.

PMID- 10964132
TI  - A difficult psychiatric patient.

PMID- 10964133
TI  - A rare case of radiculopathy in an elderly man.

PMID- 10964134
TI  - How can fruits and sugar induce headache and hypoglycaemia?

PMID- 10964135
TI  - Abdominal pain in a 22 year old woman

PMID- 10964136
TI  - A rare cause of unilateral hearing loss

PMID- 10964137
TI  - A difficult psychiatric patient

PMID- 10964138
TI  - A rare case of radiculopathy in an elderly man

PMID- 10964139
TI  - How can fruits and sugar induce headache and hypoglycaemia?

PMID- 10964140
TI  - Multiple choice questions in evidence based medicine.

PMID- 10964141
TI  - Procedure coding in anaesthesia.

PMID- 10964142
TI  - Incidence and risk factors for allogenic blood transfusion during major joint
      replacement using an integrated autotransfusion regimen. The Rizzoli Study Group
      on Orthopaedic Anaesthesia.
AB  - The efficacy of an integrated autotransfusion regimen, including pre-donation and
      perioperative salvage of autologous blood, was prospectively evaluated in 2884
      patients undergoing total hip (n = 2016) or knee arthroplasty (n = 480), and hip
      revision (n = 388) with either balanced general, regional, or integrated
      epidural/general anaesthesia. Allogenic concentrated red blood cells were
      transfused in the presence of symptomatic anaemia or when haemoglobin
      concentration was < 6 g dL-1 (10 g dL-1 in patients affected by cerebrovascular
      or coronary artery disease) after all salvaged and pre-donated autologous blood
      had been transfused. A total of 278 patients (9.6%) received allogenic blood.
      Risk factors for allogenic blood transfusion were: preoperative haemoglobin
      concentration < 10 g dL-1 (after autologous blood pre-donations) (Odds ratio:
      8.7; 95% CI: 6.5-16.8; P = 0.004), hip revision versus hip or knee arthroplasty
      (Odds ratio: 5.8; 95% CI: 3.9-8.5; P = 0. 0001) and inability in obtaining the
      number of pre-donations required by the Maximum Surgery Blood Order on Schedule
      (Odds ratio: 3.4; 95% CI: 2.7-4.1; P = 0.0001). The incidence of perioperative
      complications, including wound infection and haematoma, as well as myocardial
      ischaemia, respiratory failure and thromboembolic complications, was higher in
      those patients requiring allogenic blood transfusion (29.8%) than that observed
      in patients receiving only autologous blood (6.6%) (P = 0.0005); while the mean
      time duration from surgical procedure to patient discharge from the orthopaedic
      ward was shorter in those patients not receiving allogenic blood transfusion (12
      days; 25-75th percentiles: 8-14 days) than in those patients who required
      perioperative transfusion with allogenic blood (15 days; 25-75th percentiles: 10
      17 days) (P = 0.0005). In conclusion, this prospective study highlighted the
      clinical relevance of applying an extensive and integrated autotransfusion
      regimen in order to reduce allogenic blood transfusion and associated
      complications in patients undergoing major joint replacement.

PMID- 10964143
TI  - High-frequency jet ventilation in European and North American institutions:
      developments and clinical practice.
AB  - Respiratory support with high-frequency jet ventilation has been advocated during
      airway surgery or to improve pulmonary mechanics and gas exchange in patients
      with bronchopleural fistulae or pulmonary insufficiency. Despite a large body of
      published evidence describing its benefits as an alternative ventilatory approach
      in anaesthesia and intensive care medicine, its application has not gained
      widespread acceptance and is restricted to specialized centres. To review the
      literature on high-frequency jet ventilation in European and North American
      institutions, we performed a search in a computerized database (MEDLINE) covering
      the period from 1990 until the present time, describing the use of high-frequency
      jet ventilation in over 7000 patients. Various modes to apply high-frequency jet
      ventilation during airway surgery have been established, but its value in
      intensive care is controversial. We report our experience with combined high
      frequency jet ventilation and provide guidelines for its safe application.

PMID- 10964144
TI  - Patient-controlled analgesia and urinary retention following lower limb joint
      replacement: prospective audit and logistic regression analysis.
AB  - We studied a number of factors that may be associated with urinary retention, in
      particular the method of postoperative analgesia delivery, in 47 men and 69 women
      undergoing lower limb joint replacements. The following factors were studied:
      age, gender, height, weight, previous history of urinary retention, presence of
      symptoms suggestive of urinary tract obstruction, type of anaesthetic (general
      anaesthetic or spinal anaesthetic), type of postoperative analgesia
      (intramuscular or patient-controlled analgesia with morphine) and the total dose
      of morphine given. Urinary retention developed in 18.1% of patients. Stepwise
      logistic regression analysis was used to identify independent explanators of an
      increased probability of developing urinary retention. Three factors emerged -
      male gender, increasing age and the use of patient-controlled analgesia.

PMID- 10964145
TI  - Lidocaine 10% in the endotracheal tube cuff: blood concentrations, haemodynamic
      and clinical effects.
AB  - The purpose of this study was to evaluate the effects (common haemodynamic
      variables, peak cuff pressures, the incidence of reaction ('bucking') during
      extubation and the incidence of sore throat after operation) of lidocaine 10%
      instilled into the endotracheal tube cuff in intubated patients. Plasma
      concentrations of lidocaine were assayed. Seventy ASA class I-II patients
      scheduled for plastic surgery were studied. Patients were randomly divided in two
      groups: the cuff of the endotracheal tube was inflated with either lidocaine 10%
      (group L) or with saline (group S) immediately after endotracheal intubation. In
      group L patients, the haemodynamic changes were less (P < 0.05), and the peak
      cuff pressure was lower (P < 0.01) than for group S. At extubation, more patients
      reacted ('bucked') in group S (70.5% vs. 19.4%, P < 0.01). The incidence and
      severity of sore throat were significantly lower in group L 1 and 24-h after
      extubation. Plasma lidocaine concentrations did not reach toxic values. Lidocaine
      10%, compared with saline, in the endotracheal tube cuff was associated with less
      disturbance of haemodynamic responses and less incidence of bucking during
      tracheal extubation. Lidocaine was also effective in reducing of incidence and
      severity of sore throat after operation.

PMID- 10964146
TI  - The 50-millilitre syringe as an inexpensive training aid in the application of
      cricoid pressure.
AB  - A recent study in our department demonstrated that depressing the plunger of a 50
      mL syringe was reliably and linearly related to the force applied between 20 N
      and 50 N. Using a 50-mL syringe we constructed a simple device to help train
      anaesthetic assistants to apply cricoid pressure correctly. We then tested
      anaesthetists, operating department practitioners (non-physicians) and nurses in
      our hospital to see if they could correctly apply forces of 20 and 40 N. All
      subjects were then trained using this apparatus and once confident were retested
      immediately afterwards, and again 1 week and 1 month later. The results show a
      wide variation in the force applied with only 30% of subjects applying
      appropriate force at 20 N, and 40% at 40 N. Training leads to a significant
      improvement in performance (P < 0.005 at 20 N and P < 0.001 at 40 N) which is
      maintained for 1 week for both 20 N (P < 0.05) and 40 N (P < 0.05) but not for 1
      month. Therefore training should be practised on a weekly basis. This is an
      inexpensive and simple device that we believe to be useful in helping anaesthetic
      assistants to apply effective cricoid pressure.

PMID- 10964147
TI  - Comparison of intravenous patient-controlled analgesia with tramadol versus
      morphine after microvascular breast reconstruction.
AB  - Tramadol is a weak centrally acting analgesic and it might provide efficacious
      postoperative pain relief with minimal sedative effects in the use of intravenous
      patient-controlled analgesia (PCA). Sixty women scheduled to undergo
      microvascular breast reconstruction under standard general anaesthesia were
      enrolled in a study on the performance of patient-controlled analgesia with
      tramadol or morphine with special emphasis on drug- and technique-related side
      effects. Seven patients were re-operated within the same day, leaving 25 patients
      in the tramadol group and 28 in the morphine group for comparison. When
      postoperative pain occurred, loading doses of either 10 mg tramadol or 1 mg
      morphine intravenous increments were administered in a double-blind fashion until
      the pain control was judged to be satisfactory by the patient. After that the
      patients received tramadol or morphine by a PCA apparatus (lockout 5 min,
      tramadol 450 microg kg-1, morphine 45 microg kg-1 bolus). In addition, all
      patients received 500 mg paracetamol rectally, three times a day. The potency
      ratio of tramadol to morphine was found to be between 8.5 : 1 (loading) and 11 :
      1 (PCA). There was neither a significant difference between the groups in the
      overall satisfaction of the analgesic medication nor in the visual analogue and
      verbal rate scales for pain. Women in the tramadol group had more nausea and
      vomiting during the administration of loading doses (P < 0.05) and more patients
      in the tramadol group (7) than in the morphine group (3) (NS) wanted to
      discontinue the PCA therapy before the end of the study due to nausea. Sedation
      or blurred vision prevented the performance of the psychomotor tests in 22 and
      32% of the tramadol and morphine patients, respectively. The remaining patients
      performed similarly in the Digit Symbol Substitution Test. In women receiving
      intravenous PCA for analgesia after microvascular breast reconstruction tramadol
      and morphine provided comparable postoperative analgesia with similar sedative
      effects. However, tramadol was associated with a disturbingly high incidence of
      nausea and vomiting.

PMID- 10964148
TI  - Delivery of an hypoxic gas mixture due to a defective rubber seal of a flowmeter
      control tube.
AB  - The delivery of an hypoxic gas mixture to a patient during general anaesthesia is
      a rare event due to contemporary standards of monitoring, equipment design and
      alarm features. An incident is described where a split occurred in a rubber seal
      round the top of a flowmeter control tube. This resulted in a downstream oxygen
      leak and the delivery of an hypoxic gas mixture to the patient. The bobbin on the
      oxygen flowmeter did not accurately reflect the amount of oxygen being delivered.
      A paramagnetic oxygen analyser and a fuel cell oxygen electrode indicated that
      the inspired oxygen concentration was lower than intended. The anaesthetic
      machine was exchanged, and the operation continued uneventfully. The faulty
      anaesthetic machine subsequently passed a formal pressure test by the hospital
      engineers and also close examination of the flowmeter control valves. The
      importance of monitoring equipment and the interpretation of the information that
      they provide is emphasized.

PMID- 10964149
TI  - The analgesic efficacy and tolerance of ketoprofen (100 mg) combined with
      morphine in patient-controlled analgesia after orthopaedic surgery.

PMID- 10964150
TI  - Anaesthesia in lipid myopathy.

PMID- 10964151
TI  - Anaesthetists as echocardiographers can influence the perioperative management of
      patients with suspected aortic stenosis.

PMID- 10964152
TI  - Microalbuminuria and serum procalcitonin levels following oesophagectomy.

PMID- 10964154
TI  - A reply

PMID- 10964153
TI  - Central anticholinergic syndrome or postoperative residual block?

PMID- 10964155
TI  - Noradrenaline uptake and release by the lungs.

PMID- 10964156
TI  - HIV-1: a molecular toolkit for analysis of major histocompatibility complex class
      I expression.

PMID- 10964157
TI  - The noradrenaline plasma concentration and its gradient across the lung.
AB  - BACKGROUND: We investigated the lung contribution to circulating noradrenaline
      (NA) homeostasis. Evaluation of the transpulmonary NA gradient, related to the NA
      amount entering the lungs, is potentially important, mainly regarding clinical
      conditions, such as congestive heart failure (CHF), that are associated with
      excessive circulating NA. MATERIALS AND METHODS: 15 moderate (group 1) and 15
      severe (group 2) CHF patients, and 10 normal individuals had determination of NA
      transpulmonary gradient in the baseline and during rise (exercise, in normals and
      group 1) or fall (withdrawal from plasma by ultrafiltration, in group 2) of
      plasma NA. RESULTS: NA gradient (pg mL(-1)) at rest was 30 +/- 3 in normals, 21
      +/- 6 in group 1 and 5 +/- 8 in group 2. Increase of NA concentration in the
      mixed venous blood with exercise was paralleled by depression of the
      transpulmonary gradient. Pulmonary arteriovenous difference disappeared when NA
      entering the lungs averaged 1300 pg mL(-1). In group 2, ultrafiltration lowered
      NA in the mixed venous blood from 1225 +/- 213 to 718 +/- 182, which caused
      transpulmonary gradient to increase from 5 +/- 8 to 22 +/- 9. CONCLUSIONS:
      Transpulmonary gradient of NA diminishes when NA entering the lungs increases,
      and 1300 pg mL(-1) in the pulmonary artery is, both in patients and normal
      subjects, the level at which gradient disappears; which likely reflects cessation
      of NA uptake or achievement of a balance between lung uptake and production. This
      may have physiological and pathological implications.

PMID- 10964158
TI  - Insulin activates p38 mitogen-activated protein (MAP) kinase via a MAP kinase
      kinase (MKK) 3/MKK 6 pathway in vascular smooth muscle cells.
AB  - BACKGROUND: Induction of stress-activated mitogen-activated protein (MAP) kinases
      such as p38 could be important for the development of cardiovascular diseases
      since p38 MAP kinase activation stimulates apoptosis, cell growth, prostanoid
      formation and other cellular dysfunctions when induced by oxidants,
      hyperosmolarity, or pro-inflammatory cytokines. On the other hand, insulin
      resistance is one of the most important factors promoting atherogenesis,
      including cardiovascular diseases, but it is not clear how these different
      factors transmit their signals intracellularly at the cytosolic and nuclear
      levels. In this study, we investigated the effect of insulin on p38 mitogen
      activated protein (MAP) kinase activation in cultured rat vascular smooth muscle
      cells (VSMC). MATERIALS AND METHODS: VSMC were obtained from the aortas of male
      Wistar rats by the media explant technique. After being stimulated by insulin
      with SB-203580, PD-98059, or GF109203X, the cells were solubilized and the
      expressions of MAP kinases, MAP kinase kinases and p70 S6 kinase were examined by
      immunoblot analysis. The amount of DNA synthesis was measured by [3H]thymidine
      incorporation. RESULTS: Insulin activated p38 MAP kinase phosphorylation in a
      dose-dependent manner, and the phosphorylation was specifically inhibited by SB
      203580, a p38 MAP kinase-specific inhibitor, but not by PD-98059, a specific
      inhibitor of upstream kinase (MEK), of extracellular signal-regulated kinase
      (ERK), or GF209203X, a protein kinase C-specific inhibitor. Insulin also
      activated MAP kinase kinase (MKK) 3/MKK 6 phosphorylation, the upstream kinase of
      p38 MAP kinase, but neither stress-activated protein kinase (SAPK)/ERK kinase
      (SEK1/MKK4) nor SAPK/c-jun NH2-terminal protein kinase. Surprisingly,
      phosphorylation of p70 S6 kinase and an increase of DNA synthesis by insulin were
      suppressed dose dependently by SB-203580. CONCLUSION: These results have
      established that insulin activates the p38 MAP kinase cascade via an MKK 3/6
      pathway in rat VSMC, independently of a MEK-ERK cascade, and partly regulates
      cell growth.

PMID- 10964159
TI  - The effect of apolipoprotein B xbaI polymorphism on plasma lipid response to
      dietary fat.
AB  - BACKGROUND AND AIMS: Lipid response to dietary fat and cholesterol is, to a large
      extent, genetically controlled. Apolipoprotein B (apo B) plays a dominant role in
      cholesterol homeostasis. Several polymorphic sites within or adjacent to the gene
      locus for apo B have been detected. The X+ allele of the XbaI restriction
      fragment polymorphism of the apo B gene has been found to be associated with
      higher serum cholesterol and/or triglyceride levels. In order to study the
      influence of this mutation on the plasma lipid response in diets of varying fat
      content, 72 healthy male subjects were studied, 21 X- X- (X-) and 51 X+ (X+ X- or
      X+ X+). METHODS AND RESULTS: These subjects followed three consecutive 28-day
      diet periods: one rich in saturated fats (SAT diet; 38% fat, 20% saturated); a
      National Cholesterol Education Program type I diet (NCEP-I diet) (28% fats, < 10%
      saturated); and a third monounsaturated (MUFA diet) (38% fats, 22%
      monounsaturated). The different genotypes can be observed to have significant
      effects on total and LDL cholesterol concentrations (P < 0.017). X+ individuals
      had higher levels of total and LDL cholesterol after the consumption of a SAT
      diet (P < 0.012; P < 0.006, respectively), NCEP diet (P < 0.060; P < 0.054,
      respectively) and MUFA diet (P < 0.022; P < 0.042, respectively) in comparison
      with X- individuals. A significant interaction between genotypes and dietary
      effects was observed for diet-induced changes in plasma triglycerides (P <
      0.032). Significant decreases in the absolute values of triglyceride
      concentrations (-0.18 mmol L(-1), P < 0.024) were noted in the X- subjects after
      the high intake of a MUFA diet, while no significant differences were observed in
      the X+ individuals (0.006 mmol L(-1), P < 0.858). CONCLUSIONS: Our results
      suggest that the total triglyceride response to diet is influenced by the apo B
      XbaI polymorphism.

PMID- 10964160
TI  - Metabolic abnormalities of apolipoprotein B-containing lipoproteins in non
      insulin-dependent diabetes: a stable isotope kinetic study.
AB  - BACKGROUND: Kinetic abnormalities of apolipoprotein B (apoB)-containing
      lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM) remain poorly
      understood. To get further insight into these abnormalities we performed a stable
      isotope kinetic experiment comparing the metabolism of apoB-containing
      lipoproteins in moderately severe NIDDM patients and healthy control subjects.
      METHODS: The study was performed in the fed state. Subjects underwent a primed
      infusion of 0.7 mg kg(-1) of L-[1-(13)C]leucine followed by a 16-h constant
      infusion of 0.7 mg kg(-1) h(-1). [13C]Leucine enrichment in apoB was measured by
      gas chromatography/combustion/isotope ratio mass spectrometry. RESULTS: In NIDDM
      patients, we observed a 3.49- and 4.52-fold increase of very-low-density
      lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) apoB plasma
      concentrations, respectively (P<0.01). VLDL apoB production was increased by 41%
      (P<0.05) and fractional catabolic rate towards IDL and low-density lipoprotein
      (LDL) was decreased by 61% (P<0.05). The increased IDL apoB plasma concentration
      was also related to a major catabolic defect (-78%; P<0.01). For most patients,
      plasma LDL apoB concentration was comparable to that of controls. Nevertheless,
      LDL apoB metabolism was impaired in NIDDM subjects, with both a decreased LDL
      catabolic rate (-28%; P<0.05) and a trend towards a diminished synthesis.
      CONCLUSION: NIDDM is associated with multiple apoB metabolism abnormalities that
      are potentially atherogenic. In addition to the increased number of circulating
      VLDL and IDL particles, the increased residence time observed on all apoB
      containing lipoproteins may promote the development of atherosclerotic lesions,
      by potentiating their oxidizability.

PMID- 10964161
TI  - Differential expression of human alpha- and beta-defensins mRNA in
      gastrointestinal epithelia.
AB  - BACKGROUND: While defensins have received great attention for their role in
      bronchial innate immune defence, little is known about the expression levels of
      the four human epithelial defensins (HD5, HD6, hBD1 and hBD2) in the digestive
      tract. In this study we quantified the alpha- and beta-defensins mRNA in biopsies
      obtained from the gastrointestinal mucosa and identified the cells expressing the
      beta-defensin hBD1 mRNA in ileal mucosa. MATERIAL AND METHODS: Biopsies from
      human stomach (corpus and antrum), duodenum, jejunum, ileum and colon were
      analysed for their expression of alpha- and beta-defensins. The mRNA of defensins
      was quantified by semiquantitative reverse transcription-polymerase chain
      reaction. Cells expressing beta-defensin hBD1 mRNA were identified by in situ
      hybridization with 35S-labelled RNA probes in tissue sections of human ileum.
      RESULTS: The hBD1 mRNA was expressed at low levels with little variability
      throughout the gastrointestinal tract and was detected in all epithelial cells of
      ileal mucosa. HD5 and HD6 mRNA expression was restricted to the intestine and
      displayed high interindividual variability. The highest expression levels were
      observed in jejunum and ileum. Biopsies obtained from duodenum displayed low
      levels or no expression of HD5 and HD6. The expression level increased
      considerably in a biopsy obtained from a patient with acute coeliac sprue. In
      contrast, low levels were observed in a biopsy from a patient with coeliac sprue
      in remission. CONCLUSIONS: The expression levels of hBD1, HD5 and HD6 throughout
      the gastrointestinal tract are tissue and peptide specific and these defensins
      are expressed with high interindividual variability.

PMID- 10964163
TI  - Proximal and distal gut hormone secretion in slow transit constipation.
AB  - BACKGROUND: It has been suggested that slow transit constipation might be part of
      a panenteric disorder. Gastrointestinal peptides are involved in regulation of
      motility. DESIGN: In the present study we have evaluated whether plasma levels of
      proximal and distal gut hormones in the fasting state, and for 120 min after a
      solid meal in 29 patients with slow transit constipation are different from those
      obtained from 29 healthy controls. Plasma levels of the gut hormones
      cholecystokinin, gastrin, pancreatic polypeptide, motilin, neurotensin and
      peptide YY were determined using sensitive radioimmunoassays. In the patient
      group, oro-caecal transit time was determined by means of the hydrogen breath
      test on a separate test day. The results of transit were related with
      postprandial hormone secretion. RESULTS: Fasting plasma levels of cholecystokinin
      and pancreatic polypeptide were significantly (P < 0.05) increased in constipated
      patients. Postprandially, secretion of pancreatic polypeptide and cholecystokinin
      was significantly (P < 0.05) increased in the patients, while secretion of
      peptide YY was significantly (P < 0.05) reduced. Plasma motilin levels were not
      different between patients and controls. Altered postprandial hormone secretion
      was mainly observed in constipated patients with prolonged oro-caecal transit
      time. CONCLUSIONS: In patients with slow transit constipation, fasting and
      postprandial secretion of proximal gut hormones apart from motilin is increased
      and of distal gut hormones decreased, especially in those with severely delayed
      intestinal transit.

PMID- 10964162
TI  - A beta-turn rich oats peptide as an antigen in an ELISA method for the screening
      of coeliac disease in a paediatric population.
AB  - BACKGROUND: ELISA methods for the measurement of IgA antigliadin antibodies
      (AGA), both home-made and commercial systems, routinely employ wheat gliadin
      fractions as coating antigens. We investigate the sensitivity and specificity for
      CD diagnosis of a new ELISA method using a highly immunoreactive beta-turn rich
      gamma3-avenin peptide as an alternative coating antigen. METHODS: The assay was
      standardized with antihuman IgA peroxidase-conjugated as the second antibody.
      Alternatively, an ELISA based on the use of protein A-peroxidase was assayed to
      measure both IgG plus IgA antibodies. Sixty-three sera from healthy controls were
      analyzed to establish the system's cut-off point. Sera from 103 coeliac and from
      65 noncoeliac children were tested; for diagnosis purposes, a small intestinal
      biopsy had been performed in all of them. RESULTS: For the IgA class antibodies
      assay a high sensitivity and specificity of 90.3% and 98.5%, respectively, was
      obtained, comparable to those achieved for IgA antiendomysium antibodies (EmA)
      with the same sera. CONCLUSIONS: In view of the high sensitivity and specificity
      obtained together with water solubility of the peptide and easiness for large
      scale reproducible synthesis, the new AGA IgA avenin peptide ELISA represents a
      significant improvement in CD diagnosis in comparison with conventional
      established AGA IgA ELISA using crude gliadins as coating antigens.

PMID- 10964164
TI  - Effects of phospholipase A2, free fatty acids and 2-lysolecithin on the
      crystallization of cholesterol in gallbladder bile.
AB  - BACKGROUND: Phospholipase A2 (PLA2) and its enzymatic products free fatty acids
      (FFAs) and 2-lysolecithin are physiological constituents of bile. Their role in
      the crystallization of cholesterol in gallbladder bile of patients with
      cholesterol gallstones is still controversial. DESIGN: To clarify this issue we
      evaluated the activity of PLA2 and the concentration and pattern of FFAs in the
      gallbladder bile of cholesterol stone patients. We furthermore added PLA2, FFAs
      and 2-lysolecithin to isotropic gallbladder bile, determined the crystal
      observation time (COT) and counted the cholesterol crystals in a crystal growth
      assay for up to 21 days. RESULTS: A PLA2 activity of 1.8 +/- 1.2 U L(-1) and
      total FFA concentrations of 1.32 +/- 0.71 mmol L(-1) were determined. After
      incubation of bile for 24 h at 37 degrees C total FFAs increased to 2.72 +/- 1.29
      mmol L(-1) (P<0.005). Biliary saturated and unsaturated FFAs were found in equal
      proportions before and after incubation, pointing to an additional presence of
      lipases other than PLA2. A COTof 1 day was observed in all gallbladder biles and
      increased to 1.7 +/- 0.5 days after addition of 5 U L(-1) of PLA2 (P<0.01). An
      even higher COT of 2.5 +/- 0.8 days was seen after addition of 5 mmol L(-1) of a
      'biliary' mixture of FFAs (P<0.005) but the COT remained unchanged after addition
      of 5 mmol L(-1) of 2-lysolecithin. However, in the crystal growth assay in
      gallbladder bile addition of 5 U L(-1) of PLA2, of 5 mmol L(-1) of 'biliary' FFAs
      and of 5 mmol L(-1) of 2-lysolecithin decreased significantly the number of
      cholesterol crystals formed during follow-up. CONCLUSION: An elevated activity of
      PLA2 in gallbladder bile may counteract the formation of cholesterol crystals
      through increased formation of FFAs and 2-lysolecithin. However, regarding the
      comparatively low activity of PLA2 in gallbladder bile PLA2 seems to be of only
      minor pathophysiological importance in the formation of cholesterol gallstones.

PMID- 10964165
TI  - Semi-starvation alters myofibrillar mRNA concentrations to expedite rapid
      recovery of muscle protein stores following feeding.
AB  - BACKGROUND: Protein synthesis in skeletal muscle is reduced following starvation
      and restored by feeding. The mediators and mechanisms are incompletely
      understood. The aim of this study was to evaluate whether prolongation of
      undernutrition induced changes in muscle gene expression at the level of mRNA and
      protein. MATERIALS AND METHODS: The changes in myosin heavy-chain 2X mRNA in
      adult partially starved (50% of ad libitum standard rodent chow intake for 4 or 7
      days) C57BL mice or subsequently refed mice were studied. Ad libitum-fed mice
      were used as controls. Protein synthesis, total RNA and myosin heavy-chain 2X
      mRNA concentrations were determined. Plasma concentrations of amino acids were
      measured by high-performance liquid chromatography. RESULTS: Partial starvation
      of 4 and 7 days reduced bodyweight by 15.6 +/- 1% and 17.1 +/- 2.1% (P < or =
      0.05) vs. ad libitum fed controls. Protein synthesis was reduced by 32 +/- 9% and
      protein content by 20 +/- 4% (P < or = 0.05) following 7 days of partial
      starvation. Plasma amino acid concentrations were increased (6297 +/- 853) in
      refed animals vs. ad libitum-fed controls (3057 +/- 141, P < or = 0.05). Total
      RNA concentration (micrograms RNA micrograms(-1) DNA) in skeletal muscle was
      unchanged. Myosin heavy-chain 2X mRNA concentration did not change following 4
      days of partial starvation but increased by 24 +/- 5% (P < or = 0.05) following 7
      days of partial starvation, hence suggesting that expression of myosin mRNA was
      nutritionally altered. CONCLUSION: Postprandial stimulation of protein synthesis
      following starvation may thus be a combination of increased mRNA availability and
      increased translation. This effect may be activated by peak concentrations of
      amino acids in plasma following feeding.

PMID- 10964166
TI  - mRNA expression patterns of insulin-like growth factor system components in human
      neuroendocrine tumours.
AB  - BACKGROUND: Insulin-like growth factors (IGF) and their corresponding receptors
      and binding proteins are important in carcinogenesis for several tumours, but
      their expression pattern in the functionally and biologically heterogeneous human
      neuroendocrine tumours of the gastroenteropancreatic tract is largely unknown.
      MATERIALS AND METHODS: This study searched for the mRNA expression patterns of
      components of the IGF system: IGF-1 and IGF-2, IGF receptors 1 and 2 (IGF-1R, IGF
      2R), IGF-binding proteins 1-6 (IGFBP1-6)) in the most frequent human
      gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours
      associated with carcinoid syndrome and functionally inactive tumours) employing
      reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In the 37
      tumour samples analysed (nine gastrinomas, 10 insulinomas, nine tumours
      associated with carcinoid syndrome and nine functionally inactive tumours) IGFBP
      2 was found in all tumour samples while the IGFBP-1 was expressed only at low
      frequency (10-22%) among the four tumour types. The IGF-2R was predominantly
      expressed in gastrinomas. Among the four tumour types the expression of IGF-1R,
      IGF-2R and IGFBP-6 varied significantly. In addition, 12 pairs of significantly
      coexpressed IGF system components were detected (IGF-1 <--> IGF-1R, IGF-1 <-->
      IGF-2R, IGF-1 <--> IGFBP-3, IGF-1 <--> IGFBP-6, IGFBP-3 <--> IGF-1R, IGFBP-6 <-->
      IGF-1R, IGFBP-1 <--> IGF-2R, IGFBP-3 <--> IGF-2R, IGFBP-5 <--> IGF-2R, IGFBP-3 <-
      > IGFBP-5, IGFBP-3 <--> IGFBP-6, IGFBP-5 <--> IGFBP-6). CONCLUSIONS: The
      described differences of the expression patterns of the IGF system components in
      neuroendocrine tumour subtypes suggest tumour type-dependent different pathways
      in tumour growth control by IGF system components.

PMID- 10964167
TI  - Mechanisms of HIV-1 to escape from the host immune surveillance.
AB  - Since the beginning of the acquired immune deficiency syndrome (AIDS) pandemic in
      1981, research on human immunodeficiency virus (HIV) has been focused on
      mechanisms by which the virus escapes from immune surveillance. Several human
      leucocyte antigen haplotypes have been shown to be associated with rapid disease
      progression or resistance to disease progression. In addition, HIV is able to
      down-regulate major histocompatibility complex type I (MHC-I) on the surface of
      the host cell. For this down-regulation HIV seems to use three different
      mechanisms mediated by three different viral proteins. The viral Tat protein
      represses transcription of the MHC-I, Vpu retains nascent MHC-I chains in the
      endoplasmic reticulum and Nef mediates selective internalization of MHC-I
      molecules from the plasma membrane. The last mechanism also provides protection
      to natural killer cells that attack cells with little or no MHC-I on the cell
      surface. Together these mechanisms provide a very efficient escape from the host
      immune system.

PMID- 10964173
TI  - Interactions between nurses during handovers in elderly care.
AB  - This paper explores the role of nursing interaction within the context of
      handovers and seeks to identify the clinical discourses used by registered
      nurses, student nurses and care assistants in acute elderly care wards, to
      determine their influence on the delivery of patient care. The study design
      involved an ethnographic approach to data collection which involved: observations
      of formal nursing end of shift reports (23 handovers) and informal interactions
      between nurses (146 hours); interviews (n = 34) with registered nurses, student
      nurses and care assistants; and analysis of written nursing records. A grounded
      theory analysis was undertaken. Data were collected from five acute elderly care
      wards at a district general hospital in the south of England. Results from this
      empirical study indicate that handovers were formulaic, partial, cryptic, given
      at high speed, used abbreviations and jargon, required socialized knowledge to
      interpret, prioritized biomedical accounts and emphasized physical aspects of
      care. Patients' resuscitation status was highly salient to all grades of nurse.
      Doing 'paperwork' was accorded less status and priority than patient care, and
      was regarded as excessively time consuming. Despite this, there was evidence of
      repetition in nursing documents. Moreover, the delivery of clinical nursing
      appeared to be guided by personal records rather than formal records.

PMID- 10964174
TI  - Adjusting stroke patients' poor position: an observational study.
AB  - Although nurses' role in rehabilitation has been generally ill-defined and
      consistently undervalued, of all professional groups, nurses working with stroke
      patients have potentially the greatest contribution to make. Stroke patients are
      believed to benefit from good posture yet they can spend long periods in
      inappropriate positions. This study examined the positioning, handling and
      mobilizing of stroke patients in hospital. Non-participant observation was used
      to gather data on stroke patients' position and nurses' activities. This paper
      addresses two basic questions--what causes the adjustment of patients from poor
      to good position and who is involved in achieving this adjustment. Poor position
      was observed to end 158 times in 380 'patient hours' of observation. The most
      frequent causes of positional improvement were activities whose primary intention
      was unrelated to position correction. The deliberate adjustment of patients'
      position by nurses was a rare event which occupied a small part of nurses' time.
      The potential for a more considered and consistent nursing approach appears to be
      great.

PMID- 10964175
TI  - Liaison nursing for stroke patients: results of a Dutch evaluation study.
AB  - Liaison nurses, employed by a home care organization, were introduced into two
      Dutch hospitals to improve discharge planning for stroke patients. The main aim
      of the study presented was to gain insight into the effects of liaison nursing on
      the quality of the discharge process and related outcomes. After the introduction
      of liaison nursing, hospital nurses completed a questionnaire on satisfaction
      with the liaison nurse. In addition, both before and after the introduction of
      liaison nursing, two groups of discharged stroke patients were interviewed by
      telephone. The records of these patients were also studied with respect to
      background characteristics and duration of hospital stays. The hospital nurses
      were, generally, positive about the liaison nurse and the job she did (e.g. they
      found that home care was better organized). Further, after the introduction of
      liaison nursing, more patients stated that their post-discharge needs had been
      discussed not later than 48 hours prior to discharge, and more patients said
      their aftercare had been discussed with community nurses. However, the number of
      patients whose medication had arrived at home on time had decreased. The results
      also indicated that there was no significant difference in the duration of stay
      between the before and after group. The overall conclusion is that the liaison
      nurses have been moderately successful in their jobs. However, since the study
      was conducted in only two Dutch hospitals, findings may not be representative of
      other settings. Future research on liaison nursing is therefore recommended.

PMID- 10964176
TI  - Living with stroke: a phenomenological study.
AB  - Understanding how stroke sufferers experience their stroke and recovery is
      essential if the development of rehabilitation services is to be effective and
      appropriate. Previous research in this area has tended to be either cross
      sectional or with a limited amount of informant follow-up, and consequently has
      limited utility. This paper describes a study underpinned by a phenomenological
      approach, which tracked the experiences of six patients admitted to a
      rehabilitation unit in the north-west of England. Informants were followed for at
      least 12 months after stroke, and a total of 73 interviews were undertaken during
      the study. The data demonstrate that recovery from stroke involved restructuring
      and adaptation in physical, social and emotional aspects of an individual's life.
      Two important features of recovery were highlighted. First, whilst aspects of pre
      stroke life may be used to describe individual progress, no end-point to recovery
      was identified as informants described and anticipated life with stroke. Second,
      informants focused on the social context of recovery where engagement in the
      social world was emphasized over discrete physical function. Although no common
      path of recovery was found, it is recommended that stroke services are structured
      to take account of the long-term needs of stroke patients and their families in
      their home environment.

PMID- 10964177
TI  - Determining chest pain patients' suitability for transfer to a general ward
      following admission to a cardiac care unit.
AB  - The objective of this study was to assess the performance of a consensus-derived
      decision algorithm in determining chest pain patients' suitability for early
      transfer to a lower dependency ward by predicting complications. The sample
      comprised 516 patients with chest pain presumed to be cardiac in origin, admitted
      to a cardiac care unit (CCU) in northern England from the community or from the
      accident and emergency department. A decision algorithm was designed following a
      review of the literature and amended to take into account a clinical consensus of
      consultant physicians. Patients were assessed on admission by CCU nurses using
      the algorithm, and 'triage' decisions recorded (keep on CCU or suitable for early
      transfer to a general ward). Admission ECGs (electrocardiographs) and baseline
      clinical data were recorded independently by a researcher 'blinded' to actual
      clinical course, and applied to the algorithm using statistical software. On
      discharge or death, patients' case notes were retrieved and the hospital course
      examined for death or severe complications. Performance of the algorithm and CCU
      nurses were compared for sensitivity, specificity, positive predictive value and
      negative predictive value. The main outcome measures were death or severe
      complications occurring during hospitalization, and during the first 2 days
      following CCU admission. While sensitivity of both the algorithm (0.98) and CCU
      nurses (0.95) was high, specificity was low in both groups (0.11 and 0.21,
      respectively), making it unlikely that the algorithm would prove useful in
      clinical practice. Further studies are required to develop the optimal triage
      tool for the assessment of patients with acute chest pain.

PMID- 10964178
TI  - Patients' and carers' perceptions of factors influencing recovery after cardiac
      surgery.
AB  - Stress and anxiety experienced by patients following myocardial infarction are
      well documented. Moreover, partners feel distress when they realize that they
      must assume responsibility for day-to-day care once the period of hospitalization
      is over. However, despite the trend towards early hospital discharge and the role
      which carers appear to be expected to undertake during the recovery of patients
      who have had cardiac surgery, few studies have been undertaken with this group
      outside the United States of America. This omission was filled by a descriptive
      survey with 60 patients and carers following cardiac surgery. Data were obtained
      during early recovery (1 week after hospital discharge) and 6 weeks later. The
      results indicated that carers assumed a heavy burden once the patient had left
      hospital and were less satisfied with the timing of discharge than the patients.
      Information provided by nurses was consistently rated more highly than
      information provided by doctors or physiotherapists but there was scope for
      increasing input with both groups. High levels of satisfaction with the
      information provided by health professionals were associated with lower scores on
      the Hospital Anxiety and Depression Scale. More qualitative, in-depth studies to
      explore the precise needs of patients and their carers are needed to ensure that
      in future both groups are better prepared.

PMID- 10964179
TI  - Experiencing liver transplantation: a phenomenological approach.
AB  - In order to promote health, nurses and other health care professionals need to
      discover and articulate the meaning that is implicit in experiencing life after
      liver transplantation. From such an understanding, appropriate nursing
      interventions can be based. The aim of this study was to investigate the
      subjective experiences of the meaning of having a liver transplant, 1 year after
      the transplantation. After approval from the ethics committee at Goteborg
      University, 12 patients, nine women and three men, were interviewed. The study
      sample was chosen strategically to represent common diagnoses preceding liver
      transplantation. A phenomenological approach was chosen for the study. Analyses
      of the interviews were based on a modified version of a phenomenological method
      by Karlsson. Seven categories emerged: facing the inevitable; recapturing the
      body; emotional chaos; leaving the experts; family and friends; the threat of
      graft rejection; and honouring the donor. Having undergone a liver transplant
      meant living in a paradoxical situation. Knowing that you survived, it was a
      struggle to regain physical strength under great emotional stress. The recipients
      had to self-administer life-long medication, recognize symptoms indicating a
      potential problem and monitor for the possibility of graft rejection. Social
      support was essential for recovery. Meeting others with the same experience
      helped liver-transplanted patients to deal with their identity crises as well as
      undergo a transformation from being utterly unique to a survivor among others.
      The clinical implications from this study are that interventions, such as patient
      education, and social and mental support, are important tools to optimize both
      self-care capacity and the ability to maintain a healthy perception of identity
      after having a liver transplant at least up to 12 months post-transplant.

PMID- 10964181
TI  - British nurses in behavioural psychotherapy: a 25-year follow-up.
AB  - BACKGROUND: The National Service Framework for Mental Health has emphasized the
      need to prioritize the provision of cognitive behaviour therapy as the central
      evidence-based non-pharmacological intervention for mental health problems. For
      25 years one programme (English National Board Course No. 650--Diploma in
      Behavioural Cognitive Therapy, formerly called Nursing in Behavioural
      Psychotherapy) has trained nurses in such methods. This is the only programme in
      nursing which qualifies graduates to be fully certified as a cognitive behaviour
      therapist by the British Association of Behavioural Psychotherapy and by the
      United Kingdom Council for Psychotherapy. The practice of these nurse therapists
      (most commonly known as nurse behaviour therapists, NBTs) is the most rigorously
      evaluated in mental health nursing, with several randomized controlled trials to
      testify to clinical and economic efficacy. AIM: The aim of this study is to
      continue the systematic follow-up of all NBT graduates previously undertaken in
      two earlier surveys published in 1986 and 1994. These previous surveys examined
      clinical practice, organizational context and career and professional development
      issues. This up-to-date picture of NBTs will provide useful baselines for the
      implementation of the National Service Framework, and may be used by the
      Department of Health, education providers and services. METHOD: A postal survey
      (using the same template for categories of information as the two earlier
      surveys) was used and questionnaires were sent to 237 of the 274 trained NBTs
      whose name appears on the Central NBT Register, maintained at the Institute of
      Psychiatry/Maudsley Training Centre. RESULTS: One hundred and five of 230
      eligible respondents (45.6%) returned questionnaires and additional data were
      obtained from 27 NBTs who provided information to the Register in the year before
      the survey. Thus, some data were available for 57% of the sample. As in earlier
      surveys, it was found that the majority of therapists remain in clinical
      practice, undertake substantial further education and training and are involved
      in research and teaching as part of their overall role. The two central
      developments are an increasing move towards working in primary care and an
      increased emphasis on cognitive interventions. NBTs complete a substantial number
      of treatments per year and increasingly treat clients with difficulties not
      encountered during their basic training. NBTs now receive much more supervision
      than in previous surveys and continue to use valid and reliable measures of
      change in practice. However, the number of NBTs remains small and the impact on
      potential populations who would benefit from effective psychological
      interventions is minimal. This paper discusses the implications for service
      delivery.

PMID- 10964180
TI  - Increasing uptake rates of cervical cancer screening amongst Hong Kong Chinese
      women: the role of the practitioner.
AB  - Women's attendance for regular cervical screening has been identified as a
      significant factor in the prevention of cervical cancer. Evidence suggests,
      however, that both extrinsic and intrinsic factors influence women's attendance
      patterns for screening. Extrinsic factors, in particular the practitioner
      undertaking the screening procedure, have been shown to influence women's return
      rates for further screening. In Hong Kong, where uptake rates amongst Chinese
      women remain comparatively low, a study was undertaken to examine Chinese women's
      experiences and perceptions of cervical screening undertaken by either a female
      doctor or nurse. A multiple case study design using both qualitative and
      quantitative methods of data collection was employed. This paper reports the
      findings from the qualitative data obtained from 52 women participating in 12
      focus group interviews held in the two case studies. Thematic analysis of the
      data demonstrated the importance of the caring nature, communication skills,
      experience and expertise of the practitioner to women's attendance pattern for
      screening. The experience and expertise of the practitioner, described by women
      as teaching, minimizing pain and discomfort and being considerate, were
      considered more influential to uptake rates than the professional discipline of
      the practitioner. Findings such as these indicate the importance of the influence
      of the practitioner in determining uptake rates for cervical screening amongst
      this population group.

PMID- 10964182
TI  - Is there a concept of autonomy that can usefully inform nursing practice?
AB  - This paper examines evidence that the contemporary use of the term autonomy is
      interpreted differently by different nurses. This is important because an
      understanding of autonomy is crucial to our approach to informed consent prior to
      nursing care procedures. There are many theories of autonomy. This may account
      for various interpretations of the term amongst nurses. In this paper it is
      argued that clarity may be achieved by commitment to one particular theory of
      autonomy. It is suggested that this commitment should be the subject of further
      debate within the nursing profession. It is argued that the ambiguous use of the
      term autonomy should be replaced by a concept that has specific meaning for
      nurses and which gives a working definition to a concept that is central to
      respect for patient choice and independence.

PMID- 10964183
TI  - An investigation into the use of serum albumin in pressure sore prediction.
AB  - OBJECTIVES: To ascertain the relevance of serum albumin and serum sodium as
      predictors of pressure sores in addition to the Waterlow score. DESIGN:
      Observational study of patients at risk of developing decubitus ulcers. SETTING:
      Staffordshire, in the midlands of the United Kingdom. PARTICIPANTS: 773 elderly
      hospital in-patients of a district general hospital. MEASUREMENTS: Waterlow
      scores and serum albumin and sodium. Development of a pressure sore. RESULTS:
      Logistic regression analysis of serum albumin, serum sodium and the Waterlow
      score showed the Waterlow score and serum albumin were significant predictors of
      pressure sores. CONCLUSIONS: Serum albumin may, in this patient group (in
      patients over 64 years of age), be a useful predictor of pressure sore
      occurrence, though further work is needed to establish whether this is the case.
      Risk assessment of pressure sores can possibly be improved by adding serum
      albumin to one of the pre-existing tools such as the Waterlow score.

PMID- 10964184
TI  - The psychometric properties of the Miller Behavioural Style Scale with adult
      daughters of women with early breast cancer: a literature review and empirical
      study.
AB  - Several researchers have suggested that the information-seeking behaviours of
      patients need to be taken into consideration when assessing their information
      needs. This study reviews published evidence of the psychometric properties of
      the Miller Behavioural Style Scale, a tool commonly used to identify the
      information-seeking behaviours of individuals under threat, and examines its
      reliability and validity with adult daughters of women with early breast cancer.
      Ninety-seven adult daughters completed the MBSS and a 30-item, self-administered
      questionnaire, a tool designed to explore the information needs of adult
      daughters of women with breast cancer. The internal consistency of the monitoring
      and blunting sub-scales of the MBSS was alpha = 0.65 and 0.41 respectively. The
      blunting sub-scale fell substantially below acceptable limits and was discarded
      from subsequent analyses. The monitoring sub-scale possessed good test-retest
      reliability (n = 17) with a 5-week time interval (r= 0.71, P < 0.005), as
      measured using a Pearson's correlation coefficient. Furthermore, the majority
      (73.4%) of monitoring items possessed moderate or substantial test-retest
      reliability, as indicated by kappa coefficients. Finally, the monitoring sub
      scale possessed good construct validity, both discriminant and convergent
      validity, as measured by the univariate associations between monitoring behaviour
      and selected items from the information questionnaire and a demographic
      questionnaire. In conclusion, adequate support exists for the psychometric
      properties of the monitoring sub-scale of the MBSS and its use with adult
      daughters of women with early breast cancer in future research. These findings
      have a number of implications for nursing research and these are discussed in
      this paper.

PMID- 10964185
TI  - Respondent-generated quality of life measures: useful tools for nursing or more
      fool's gold?
AB  - Within health services research the quest for better ways of measuring quality of
      life as an outcome variable continues apace. Recent developments in this area
      have seen increasing attempts to incorporate individually generated content and
      values into quality of life measures while retaining valid psychometric
      measurement properties. Following a brief overview of current conceptual
      approaches to quality of life measurement, this paper reviews the development of
      two leading Respondent-generated instruments: the Schedule for the Evaluation of
      Individual Quality of Life (SEIQoL) and the Patient Generated Index (PGI). The
      relative strengths and weaknesses of these tools and their potential applications
      for nursing and nursing research are appraised. These measures both address and
      manifest a number of fundamental conceptual and methodological problems, and
      represent an innovative attempt to square the quantitative--qualitative circle.
      As such they offer challenging opportunities for nursing at a number of levels.
      Their elicitation and quantification of individual components of quality of life
      offer opportunities for nurses to plan care and goal set with patients. As yet,
      however, the validity, reliability, responsiveness and practicality of these
      instruments as outcome measures are debatable and require further testing. Nurse
      researchers could contribute to this process by using Respondent-generated
      measures as an adjunct to existing, established tools in outcome studies.
      Moreover, nursing is well placed to investigate and debate the validity of the
      conceptual assumptions underpinning these new instruments.

PMID- 10964187
TI  - Disability, nursing research and the importance of reflexivity.
AB  - Reflexivity has been viewed as a way of promoting quality within the research
      process. Its importance is highlighted in both the literature concerning nursing
      research and that which relates to disability research. However, whilst disabled
      people comprise a key client group for nurses the need for nurse researchers
      working in this field to adopt a reflexive approach to their work has not been
      explored in depth. In this paper the relevance of reflexivity to nursing research
      is discussed and current debates concerning disability research are explored. It
      is argued that there are particular reasons why it is necessary for nurse
      researchers to adopt a reflexive approach when focusing on disability. First,
      there is a need to examine closely the definitions of disability which underpin
      our research and practice. Second, it is noted that nurse researchers may be
      viewed as part of a system which disables people with impairments. Finally, it is
      important to reflect critically upon whose interests are served by such research.
      Some strategies for promoting reflexivity are also explored. It is concluded that
      a failure to address these issues via a process of critical reflection may mean
      that nursing research is viewed as unhelpful by disabled people. This in turn has
      implications for nursing practice.

PMID- 10964186
TI  - Practical considerations in case study research: the relationship between
      methodology and process.
AB  - This paper explores the extent to which the design of a research study is
      influenced by pragmatic as well as theoretical considerations by describing the
      authors' experience of conducting multiple case studies in the context of a
      policy-orientated research project. The case studies in question formed part of a
      collaborative project exploring the development of innovative roles in nursing
      and the professions allied to medicine. The researchers adopted Yin's approach to
      the conduct of multiple case studies to explore issues relating to the
      effectiveness of new roles, their resource implications and educational issues
      surrounding their development. They address the fact that methodological
      decisions have practical implications and also explore the effects of practical
      and ethical issues on research design. Three purposively selected acute National
      Health Service Trust hospitals in England formed the case study sites for the
      work recorded in this paper. In each Trust, three nursing roles were selected,
      making nine cases for study. A variety of data collection strategies were used
      including semi-structured interviews with post-holders and other stakeholders (n
      = 51), non-participant observation of meetings, collection of audit, financial
      and statistical data and review of relevant documentation. This paper describes
      some of the dilemmas which arose during the course of the study, the rationale
      for methodological decisions taken to resolve these dilemmas and the steps taken
      to enhance rigour. In particular, the authors discuss the problems associated
      with obtaining informed consent in the context of qualitative research and with
      member validation of transcripts in a context where confidentiality was crucial.
      The decision to present findings thematically rather than as individual cases is
      justified both in terms of the nature and purpose of the research and in relation
      to the particular importance of anonymity and confidentiality in this study.
      Finally, the degree of reciprocity between researcher and researched is
      discussed.

PMID- 10964188
TI  - The use of randomized control trials in complementary therapies: exploring the
      issues.
AB  - The current popularity of complementary therapies presents an interesting
      challenge to nurses and midwives. If they are to deliver such therapies
      themselves, or support patients in choosing appropriate therapies they will need
      to consider the professional and legal issues, in particular those regarding
      safety. Evidence for the effectiveness for complementary therapies is also a
      requirement in order that their integration into nursing practice can be
      justified. Purchasers are currently hampered by the lack of credible evidence for
      effectiveness and until that evidence is provided, access to such therapies
      through the National Health Service (NHS) will remain limited. The form that
      evidence should take has led to a lively debate about possible methodological
      approaches. There appears to be a clash between the medical profession and those
      working in the field of complementary therapy research, with the medical
      establishment advocating randomized control trials (RCTs). This contrasts with
      the view held by some advocates of complementary therapies that the RCT approach
      is reductionist and not applicable to such approaches. The pivot of the debate on
      the methodological approaches for evaluating complementary therapies is the
      contrast of two apparently different and diverse world-views, and the assertion
      that methods developed in one world-view are not transferable to the other. There
      is also some confusion within the field of complementary therapy over the
      applicability of RCTs to therapies such as acupuncture, and the mistaken
      assumption that trials which include a control group, are also required to be
      double-blind. This paper is based on the need for good quality evidence of
      effectiveness in complementary therapy. It will set out the concerns associated
      with the use of RCTs within complementary therapy, together with the benefits and
      limitations of this approach. The paper will go on to review research options and
      propose some suggestions for future methodological approaches.

PMID- 10964189
TI  - Minimizing postpartum pain: a review of research pertaining to perineal care in
      childbearing women.
AB  - This paper provides a review of literature that relates to perineal pain and
      care. Articles evaluated include systematic reviews and research papers from the
      disciplines of midwifery, physiotherapy and obstetrics. The major themes to
      emerge from the literature and be reviewed are the need for episiotomy, suturing
      methods and materials, assessment of perineal trauma, treatment of perineum in
      the postpartum period, and postpartum recovery. Research has highlighted that
      many practices relating to perineal care remain un-researched and therefore the
      need for evaluation is urgent. Further postpartum morbidity has been seen to
      affect many women, but is often unrecognized by practitioners. It is also a topic
      that requires further evaluation through well-designed and implemented research.

PMID- 10964190
TI  - Systematized HIV/AIDS education for student nurses at the University of Ibadan,
      Nigeria: impact on knowledge, attitudes and compliance with universal
      precautions.
AB  - This paper reports the findings of a study which examines changes in a group of
      Bachelor of Science (BSc) nursing students' perceptions, knowledge of and
      attitudes towards human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS), accruing from attempts at a systematized education for the cohort.
      Based upon a 3-month study of 141 registered nurses enrolled in a BSc nursing
      programme at the University of Ibadan, Nigeria, it investigates alterations in
      knowledge and attitudes resulting from intense instruction on HIV/AIDS, AIDS
      patient care, and compliance with universal precautions. With regard to knowledge
      enhancement and attitudinal transformation, the research reveals that a number of
      positive changes occurred over the period of the study. Not only were the nurses
      better informed about AIDS than previously, but their attitudes towards the
      disease and patient care had become considerably more liberal, as well as their
      disposition to comply with universal precautions. The conclusion emphasizes that
      it is very important for education about HIV/AIDS to be incorporated within
      current undergraduate and in-service training programmes for Nigerian nurses.

PMID- 10964191
TI  - Training programme in techniques of self-control and communication skills to
      improve nurses' relationships with relatives of seriously ill patients: a
      randomized controlled study.
AB  - The interpersonal relationships with relatives of seriously ill patients may
      cause anxiety on the part of nurses and the need for adequate communication and
      self-control skills. To assess the efficacy of training nurses in self-control
      techniques and communication skills when they interact with relatives of
      seriously ill patients we planned a randomized, controlled trial in two parallel
      groups: an experimental group, with immediate training, and a control group, with
      training delayed for 6 months. We recruited 61 nurses from the nursing staff of a
      university hospital of 500 beds. The intervention consisted of training in
      relaxation, cognitive restructuring and some communication skills. The outcome
      variables were communication skills measured under simulated conditions using an
      observation instrument of our own, administered by observers masked with respect
      to the study groups, and the levels of state-anxiety measured with the self
      assessment questionnaire the State-Trait Anxiety Inventory, under imaginary
      conditions. The two groups initially had similar scores in the scales of
      communication skills, and state and trait-anxiety. After intervention, compared
      with the control group, the experimental group showed significant improvements in
      the skills of listening, emphasizing, interrupting and coping with emotions (P <
      0.05). State-anxiety levels did not show any changes. In conclusion, the joint
      training in self-control and communication improves some communication skills in
      nurses when they interact with relatives of seriously ill patients under
      simulated conditions.

PMID- 10964192
TI  - Should service providers be paid for providing pre-registration clinical
      placements?
AB  - The authors have argued elsewhere that second- and third-year student nurses and
      midwives on ward-based clinical placements make a service contribution which is
      of significant value to the service provider. The value of the service
      contribution made by students in community-based clinical placements is lower,
      not least because such placements cannot free staff time in the same way as on
      the wards, and thus the presence of students appears to form a cost to the
      service provider. It is clear that there is no case for introducing a system of
      payments for ward-based placements, but in community-based placements the
      position is less obvious. The argument hinges upon the perceived value to the
      service provider of the qualitative benefits associated with the presence of
      students on placement. Other studies have suggested that these benefits are such
      as to outweigh the associated costs. Because the presence of students on clinical
      placement is associated with both costs and benefits, efforts should be made to
      ensure that both ward-based and community-based placements are distributed as
      fairly as possible between locations so that no one location is unduly advantaged
      or disadvantaged by the number of students which it receives.

PMID- 10964193
TI  - Suicide and self-harm in inpatient psychiatric units: a national survey of
      observation policies.
AB  - There is little empirical literature on observation as a psychiatric nursing
      procedure to prevent patients from harming themselves or others. National
      guidelines for this practice do not exist, with a consequence that local policies
      might be variable in content and quality. This paper reports a national survey of
      observation policies and usage based upon a stratified random sample of 27
      psychiatric inpatient service providers in England and Wales. Extreme variation
      in terminology and practice was encountered. The terminological confusion is
      likely to reduce nurses' clarity about their responsibilities and increase risks
      to patients. Further variation exists from place to place as to whether, and to
      what extent, student nurses and family members should be entrusted with the
      responsibility to observe patients. More than one in 10 services of the sample
      still have no written observation policy, and four in 10 have no clinical
      recording system of the procedure in place. Nurses commonly amend the procedure
      and terminology on an ad hoc basis. The results of this survey confirm that the
      Department of Health should set national standards for the policies and
      procedures for patient observation and that as an interim step practice guidance
      should be issued to all nurses (and other mental health workers) involved in this
      procedure.

PMID- 10964194
TI  - Child care responsibilities and participation in continuing education and
      training: issues relating to motivation, funding and domestic roles.
AB  - Changes in the organization and funding of health services and in the education
      and training of NHS staff have placed increased influence in the hands of
      employers and individual students as users of continuing professional
      development. Against this policy context an interview study was carried out with
      students participating in a range of continuing professional development
      activities. The sample included 89 participants attending a range of courses.
      Approximately half of the sample had children. Many of the participants were
      attending courses in their own rather than in their employers' time and several
      were self-funding. The influence of domestic responsibilities on motivations,
      along with the impact of course participation on home and family life, were
      examined. Results revealed that those with children were less likely to perceive
      continuing education in a positive light compared to those without. The impact of
      course participation on home and family life was invariably negative and for some
      the consequences were serious. The policy implications of findings are discussed.

PMID- 10964195
TI  - A model of burnout and life satisfaction amongst nurses.
AB  - This study, among 109 German nurses, tested a theoretically derived model of
      burnout and overall life satisfaction. The model discriminates between two
      conceptually different categories of working conditions, namely job demands and
      job resources. It was hypothesized that: (1) job demands, such as demanding
      contacts with patients and time pressure, are most predictive of exhaustion; (2)
      job resources, such as (poor) rewards and (lack of) participation in decision
      making, are most predictive of disengagement from work; and (3) job demands and
      job resources have an indirect impact on nurses' life satisfaction, through the
      experience of burnout (i.e., exhaustion and disengagement). A model including
      each of these relationships was tested simultaneously with structural equations
      modelling. Results confirm the strong effects of job demands and job resources on
      exhaustion and disengagement respectively, and the mediating role of burnout
      between the working conditions and life satisfaction. These findings contribute
      to existing knowledge about antecedents and consequences of occupational burnout,
      and provide guidelines for interventions aimed at preventing or reducing burnout
      among nurses.

PMID- 10964196
TI  - Midwives' support needs as childbirth changes.
AB  - This paper reports on midwives' support needs as they were described by midwives
      in a large study of the supervision of midwives in England. The data are derived
      from six sites: five, very different, National Health Service (NHS) sites, and
      one composed of midwives outside the NHS. In-depth, ethnographic interviews were
      conducted with 168 midwives and a grounded theory approach was used for the
      analysis. The findings identified midwives' many and varied support needs.
      Midwives also clearly described the culture of midwifery in the NHS. This culture
      inhibited midwives from arranging to have their support needs met and acted as an
      obstacle to progress in developing midwifery practice. The dilemmas and tensions
      inherent in this situation are explored and suggestions made as to the way
      forward.

PMID- 10964197
TI  - Still fumbling along? A comparative study of the newly qualified nurse's
      perception of the transition from student to qualified nurse.
AB  - An earlier study conducted in the United Kingdom, examining the newly qualified
      nurse's perception of the transition from student to qualified nurse, highlighted
      the limitations of pre-registration nurse education in respect of failing to
      provide adequate preparation for the qualified nurse's role. In the intervening
      years, major reforms in pre-registration nurse education and continuing
      professional education have occurred. Concomitant with these reforms have been
      major policy changes in health care delivery that have impacted upon the role of
      the nurse. Questions now arise as to whether the education reforms have served to
      equip newly qualified nurses more appropriately with the necessary knowledge,
      skills and confidence to function in contemporary health care settings. This
      paper presents the findings of a follow-up study that entailed a secondary
      analysis of exiting data obtained from in-depth interviews with 10 newly
      qualified nurses in 1985 and collecting additional data from 25 newly qualified
      nurses in 1998 in order to ascertain their perceptions of the transition from
      student to qualified nurse. Interview transcripts from both sources of data were
      coded and thematically analysed and comparisons made between the two sets of
      data. The paper focuses on one theme emanating from the original study. Entitled
      'fumbling along', it described the haphazard manner whereby the nurses learned to
      perform their role in the light of what they perceived to be inadequate
      preparation and lack of support. Similarities and differences in the experiences
      and perceptions of the two cohorts of nurses are examined in respect of stressful
      aspects of the role, pre-registration preparation and post-registration
      development. Data from the follow-up study suggest that although newly qualified
      nurses still feel inadequately prepared for their role, they have developed a
      more active style of learning and when supported through a preceptorship scheme
      appear to find the transition less stressful than nurses in 1985. However,
      further attention needs to be paid to the development of clinical, organizational
      and management skills in pre-registration courses and the bridging period between
      the latter part of the course and the first 6 months post-qualification, in order
      to enable the neophyte nurse to acclimatize gradually to becoming an accountable
      practitioner.

PMID- 10964198
TI  - Crosscurrents: against cultural narration in nursing.
AB  - Nurses, like other groups throughout history, have been described as an oppressed
      group. Writers who describe nurses as lacking in self-esteem, autonomy,
      accountability and power support this view in the literature. Indeed the cultural
      narration of nursing is for nurses to be subordinate. This article explores the
      emergence of horizontal violence within nursing and suggests that it is a result
      of unexpressed conflict within an oppressed group. The author aims to raise the
      awareness of horizontal violence in nursing so that practitioners come to
      understand how this in itself can be an expression of power. Drawing upon
      theories of reflective practice, the article examines how the educational system
      in nursing may have contributed to the felt oppression within the group by
      colluding with the cultural narrative. The crosscurrents of cultural narration
      are strong and it is argued here that the nurse needs to feel empowered in order
      to take action to swim against the tide. The author proposes that a model of
      transformatory learning based upon critical theory creates the possibility of
      emancipatory action in nursing, both locally and globally.

PMID- 10964200
TI  - In this issue

PMID- 10964199
TI  - Care pathways: an evaluation of their effectiveness.
AB  - This paper reports on a quasi-experimental case study of two care pathways--a
      midwifery-led maternity pathway and a breast disease pathway developed within one
      British National Health Service Trust. Of the aspects evaluated, those reported
      here are: a comparison of clinical care delivered before (the control group) and
      after the introduction of the two pathways; a comparison of patient satisfaction
      levels before (the control group) and after the introduction of the two pathways;
      and views of staff involved in the development and operation of the two pathways.
      The results are mixed. In the breast disease pathway five of 12 clinical
      indicators showed change, but only two of these showed statistically significant
      changes; three were considered of clinical significance but could not be tested
      statistically. In the maternity pathway, after allowing for the effect of gravid
      status, five of 10 indicators showed changes between the pre-pathway and pathway
      users and of these four showed statistically significant changes. Patient
      satisfaction levels showed little overall change--only 15% of the questions for
      breast disease and 9% for maternity showed any statistically significant change.
      However, both surveys indicated precise areas where a change resulting from the
      introduction of the pathway could be linked to an increase in satisfaction. The
      clinical staff interviewed highlighted many positive features of the tool (26/40
      comments). The most frequently cited favourable comment was its ability to make
      staff focus on the clinical care they were providing and how this could be
      improved. It also highlighted some areas for concern, in particular the
      introduction of pathway documentation.

PMID- 10964201
TI  - Asking questions - improving teaching.

PMID- 10964202
TI  - The place of the basic sciences in medical curricula.

PMID- 10964203
TI  - The decline and fall of humanism in medical education.

PMID- 10964204
TI  - If you want the surgery done well, get a woman to do it!

PMID- 10964205
TI  - Defining international standards in basic medical education: the World Federation
      for Medical Education has initiated a timely discussion.

PMID- 10964206
TI  - A surgical career? The views of junior women doctors.
AB  - OBJECTIVE: To explore female pre-registration house officers (PRHOs) views of
      surgery as a possible career choice. DESIGN AND PARTICIPANTS: In this qualitative
      study in-depth semistructured interviews were carried out with 15 female PRHOs.
      They were part of a larger sample of 24 PRHOs (15 women and nine men) who were
      being interviewed primarily to explore their ways of learning in both hospital
      and general practice settings. This paper focuses on the responses of the 15
      women in relation to surgery as a possible career choice. METHODS: Interviews
      incorporated a checklist of topics to encourage participants to discuss their
      experiences of learning and working as PRHOs, including factors which had
      impacted on future career choices. Common themes were identified by comparing
      narratives. RESULTS: Only three of the 15 women PRHOs were considering a career
      in surgery. The importance of positive surgical placements and contact with
      female surgical registrars and consultants during undergraduate training was
      highlighted. The changing nature of the surgical PRHO job with its lack of
      surgical exposure was unlikely to change the future career plans of female PRHOs.
      Factors such as the perceived difficulties of combining a family with a surgical
      career and the lack of women in particular surgical specialties were of
      considerable concern. CONCLUSIONS: Strategies for ensuring that female medical
      students receive a more positive view of surgery need to be implemented. Surgical
      PRHO jobs should be re-evaluated to assess the surgical experience being gained
      by doctors, particularly in light of the reduction in junior doctors' hours.
      Despite policy initiatives, many newly qualified women doctors have already
      decided against a surgical career.

PMID- 10964207
TI  - The role of basic sciences in a problem-based learning clinical curriculum.
AB  - BACKGROUND: Very little is known about the use of problem-based learning (PBL)
      during the later years of the undergraduate medical course and how it influences
      further acquisition of basic science knowledge. Similarly to many other
      Faculties, the PBL approach is used at Manchester in years 1 and 2, but more
      unusually, the curriculum continues to be centred on PBL in the clinical modules.
      OBJECTIVES: To explore whether and how basic science learning was continued in
      year 3 of the PBL clinical curriculum. METHODS: 10 of the weekly problems from
      the two core modules in year 3 were analysed to determine: (a) whether the design
      teams were using basic science objectives in devising the problems, and (b)
      whether PBL student groups were setting basic science learning objectives. The
      basic science knowledge of year 3 and 4 students was also measured. RESULTS:
      Similar numbers of objectives were being set by the management groups for each
      weekly problem (Heart, lung and blood (HLB) module, median 15, range 11-20;
      Nutrition, metabolism and excretion (NME) module, median 13, range 9-21). In the
      basic sciences, there was a median of 3 objectives per problem (range 0-6) in the
      NME module, but only 1 objective (0-2) per problem in the HLB module. The
      objectives set by six PBL groups in each module were analysed. Overall, agreement
      was reached on 130 occasions (62%) between the design team basic science
      objectives and those set for themselves by the student groups. In addition, there
      was a median of 2 (range 1-8) new basic science objectives brought out by the PBL
      groups that were not listed by the HLB module design team. In the NME module,
      there was again a median of 2 new objectives (range 0-6). The performance of year
      3 and year 4 students in the multiple-choice questions progress test was
      analysed. For the 65 basic science questions, the year 3 mark was 40.8 +/- 12.3%
      compared with 57.1 +/- 12.3% for year 4 (P < 0.0001). CONCLUSIONS: (a) The design
      teams are setting basic science objectives; (b) the working problems are
      triggering students to set learning objectives in the basic sciences; (c) most of
      the objectives being set by the design teams are being triggered in the majority
      of group sessions; (d) the students knowledge of basic sciences increases in
      years 3-4.

PMID- 10964208
TI  - The influence of assessments on students' motivation to learn in a therapy degree
      course.
AB  - PURPOSE: This paper reports a study which attempted to examine the influence of a
      varied assessment programme on student motivation to learn in an undergraduate
      therapy degree course. METHODS: In March 1997 a questionnaire was distributed to
      98 third-year occupational therapy and physiotherapy students at the Southampton
      University School of Occupational Therapy and Physiotherapy. Using closed and
      open questions the questionnaire required the students to consider all the
      assessments they had taken in their 3 years of study and provide information
      about which type of assessment they found most motivating for their learning, and
      why. RESULTS AND CONCLUSIONS: The results revealed that students found a wide
      range of assessments motivating. There was some satisfaction with the mix and
      range of assessments. Three assessments emerged as the most motivating for
      student learning: Clinical/fieldwork II and III and Methods of inquiry III. In
      addition, four factors associated with assessment appeared to influence student
      motivation: perceived relevance and content of the assessment, enthusiastic
      lecturers and group influences. These factors need to be explored in more detail
      but in order to do so, educators need to be prepared to engage in an open
      dialogue with students about the learning climate that is created within higher
      education.

PMID- 10964209
TI  - What do medical students read and why? A survey of medical students in Newcastle
      upon-Tyne, England.
AB  - OBJECTIVES: There is increasing interest in the role of medical humanities within
      the undergraduate curriculum, but we know little about medical students' views on
      this or about their reading habits. Our study explored the reading habits of
      medical students, and their attitudes towards literature and the introduction of
      humanities into the curriculum. DESIGN: Self-completion questionnaire survey.
      SETTING: Newcastle University and Medical School. SUBJECTS: All first-, second-
      and third-year undergraduate medical students (384), biology students (151) and a
      random sample of law students (137) were sent a self-completion questionnaire to
      assess reading levels, attitudes towards literature and the medical humanities
      (medical students) and the perceived benefits of reading. RESULTS: Medical
      students read widely beyond their course and articulate a range of benefits from
      this, including: increasing awareness of life outside their experience;
      introspection or inspiration; emotional responses; and stimulation of an interest
      in reading or literature. Of the medical students, 40% (103/258) read one or more
      fiction books per month, but 75% (193) read fewer non-curricular books since
      starting university, largely because of time pressures, work, study or academic
      pressures and restricted access to books. A total of 77% (194) thought that
      medical humanities should definitely or possibly be offered in the curriculum,
      but of these 73% (141) thought it should be optional and 89% (172) that it should
      not be examined. CONCLUSIONS: Medical students read literature for a variety of
      very positive and valued reasons, but have found leisure reading harder to
      maintain since starting university. They support inclusion of the humanities in
      medical education, but have mixed views on how this should be done.

PMID- 10964210
TI  - Medical faculty as humanistic physicians and teachers: the perceptions of
      students at innovative and traditional medical schools.
AB  - BACKGROUND AND OBJECTIVES: The training of caring physicians represents an
      important goal of medical education. Little is known however, on whether medical
      faculty constitute good role models for teaching humanistic skills to medical
      students. In this study, we examined to what extent medical students at
      innovative and traditional schools perceived their teachers as humanistic
      physicians and teachers. We also explored whether pre-clinical and clinical
      students shared the same perceptions. METHODS: A mail survey was conducted in
      Canada of all second-year students and senior clerks at one innovative medical
      school (problem-based learning (PBL), patient-centred, community-oriented) and
      three traditional medical schools. Students were asked to what extent they agreed
      or disagreed that the majority of their teachers behaved as humanistic physicians
      and teachers; 10 statements were used. Overall, 65% of the 1039 students returned
      the questionnaire. RESULTS: Over 25% of second-year students and 40% of senior
      clerks did not agree that their teachers behaved as humanistic caregivers with
      patients or were good role models in teaching the doctor-patient relationship.
      More than half of second-year students and senior clerks did not agree that their
      teachers valued human contact with them or were supportive of students who had
      difficulties. There were few differences in the way medical students at
      innovative and traditional schools perceived their teachers' humanistic
      qualities. At the pre-clinical level however, there were more students from the
      innovative school than from the traditional schools (around 60% vs. 40%, P <
      0.005) who agreed that their teachers valued human contact with them and were
      supportive of students. CONCLUSION: Our results indicate that the PBL curriculum
      fosters better teacher-student relationships during the pre-clinical years. They
      also suggest that an unacceptably large number of medical students are taught by
      physicians who seem to lack compassion and caring in their interactions with
      patients. This study questions the adequacy of medical faculty as role models for
      the acquisition of caring competence by medical students.

PMID- 10964211
TI  - Students, tutors and relationships: the ingredients of a successful student
      support scheme.
AB  - BACKGROUND: Medical students suffer from stress and psychological morbidity. Much
      of this stress is related to uncertainty about course work and workload. Although
      several student support systems are on offer at various medical schools, few have
      been shown to meet the needs of students. OBJECTIVE: To evaluate one student
      support scheme and determine the factors which are essential for success. METHOD:
      A total of 144 second- and third-year medical students were randomly selected at
      the University of Dundee. They were asked to complete questionnaires regarding
      contact with their personal tutors, frequency of meetings, activities during
      meetings, opinions on how to improve the system and how satisfied they were with
      the present system. In addition 28 tutors were also asked to complete a
      questionnaire which matched as far as possible that for students. Qualitative
      data was collected from semi-structured interviews, free-text responses from
      questionnaires, email communications with student group representatives and
      telephone interviews. RESULTS: The scheme was rated as successful or very
      successful by 25 (18.4%) students and five (29.4%) tutors. A high success rating
      was associated with regular and frequent meetings, with tutors actively seeking
      their students and taking part in social as well as academic activities.
      CONCLUSIONS: The relationship that is formed between students and tutors is the
      most important factor contributing to the success of the scheme. Taking part in
      social activities encourages the relationship to develop, whilst addressing
      academic problems helps to meet the needs of students. Those students who fail
      exams appear to have the same needs as those who pass.

PMID- 10964212
TI  - The evaluation of undergraduate students' written English language skills.
AB  - CONTEXT: Writing is an important skill for practitioners and students, yet this
      is a skill rarely taught in a formal capacity at medical school. At the
      University of Adelaide many students are from non-English speaking backgrounds
      and have varying proficiencies in English. We wished to devise a method and
      instrument which could identify students who may benefit from formative feedback
      and tuition in writing. OBJECTIVES AND METHOD: Students' written account of a
      short clinical interview with a standardized patient was assessed using a new
      instrument (the Written Language Rating Scale) designed especially for this
      study. The assessment of writing was made by one rater with qualifications in
      teaching English as a second language. SUBJECTS: 127 second-year medical students
      enrolled at the University of Adelaide, Australia. INSTRUMENTS AND RESULTS: The
      scale appeared to have good internal consistency, face and construct validity,
      and test security was not an issue. However, it had questionable concurrent
      validity with a standardized language test, although this may be partly due to
      the period of time which had elapsed between administration of the two tests.
      CONCLUSIONS: This study was useful in providing a means to objectively rate
      students' written English language skills and to target students in need of
      formative feedback and tuition. However, further research is necessary for both
      evaluation of medical writing and interventions for its improvement.

PMID- 10964213
TI  - Students' perceptions of the relative advantages and disadvantages of community
      based and hospital-based teaching: a qualitative study.
AB  - AIMS: To obtain the perceptions of first-year clinical medical students of the
      relative advantages and disadvantages of community-based and hospital-based
      clinical teaching. METHODS: A qualitative study. A purposive sample of first-year
      clinical medical students who had experienced both community-based and hospital
      based teaching was invited to participate in individual semistructured interviews
      or focus groups. Interviews and focus groups were audiotaped and transcribed to
      facilitate content analysis of the data. A total of 24 students participated in
      individual interviews and a further 18 took part in focus groups. RESULTS:
      Respondents identified advantages and disadvantages specific to teaching in each
      setting. Chief advantages of hospital-based learning were perceived to include
      learning about specialties and the management of acute conditions, and gaining
      experience of procedures and investigations. Community-based learning was
      perceived as particularly appropriate for learning about psychosocial issues in
      medicine, for increasing students' awareness of patient autonomy and for
      improving communication skills. In addition, aspects of organization and of
      teaching methods employed by community tutors, although not site-specific, were
      viewed as conducive to a positive educational experience. Students perceived some
      areas, such as clinical skills acquisition, to be equally well learned in either
      setting. DISCUSSION: As community-based teaching forms a greater proportion of
      the undergraduate medical experience, medical educators must find ways of
      determining the specific advantages that community and hospital settings can
      contribute to undergraduate learning and of using these resources effectively to
      develop comprehensive and integrated curricula. Innovations in teaching methods
      may also be necessary to provide an effective educational experience and promote
      active learning.

PMID- 10964214
TI  - Medical students' concerns about communicating with patients.
AB  - BACKGROUND: Only limited information is available on students' concerns regarding
      communication with patients. SAMPLE AND DESIGN: A total of 16 concerns regarding
      communicating with patients were rated by 179 third-year medical students, before
      the students had any contact with patients and before communication skills
      teaching had begun. At the end of the term, the ratings were collected again from
      139 of the students. The concerns were derived from the list by Cohen-Cole and
      from a previous pilot study. RESULTS: All concerns diminished significantly by
      the end of the term, but their order remained similar. At both time points,
      concerns about dealing with patients who are in pain or show strong negative
      emotions received the highest ratings. CONCLUSION: Communication skills courses
      need to focus on helping students to cope with distressed patients.

PMID- 10964215
TI  - Teaching medical students about disability and rehabilitation: methods and
      student feedback.
AB  - The predicted increase in the prevalence of chronic and disabling diseases in the
      population over the next 30 years calls for a more effective approach to
      educating medical students about the assessment and management of disability. The
      introduction of a new postgraduate medical course at Flinders University of South
      Australia in 1996 allowed the development of a new topic on disability and
      rehabilitation. Over a 4-week period, students undertake four activities. First,
      they follow a particular patient in an inpatient rehabilitation setting and learn
      about the multidisciplinary approach to rehabilitation. Secondly, they each visit
      two people with a disability living in the community and assess their physical,
      mental, functional and social status. Thirdly, they each visit a service which
      supports those people in the community. Finally, they simulate having a
      disability which is randomly allocated to them. During these 4 weeks, students
      also participate in problem-based learning (PBL) and have 27 h of associated
      sessions or lectures. The PBL cases and associated sessions have a 'chronic
      disease' theme. We developed a questionnaire to obtain student feedback on this
      new topic in the first 2 years of its delivery. A 69% response rate has been
      obtained. Overall, the topic was well-received, and as a result most students
      felt more comfortable in dealing with disabled people. They were enthusiastic
      about ward work, and enjoyed learning about aspects of multidisciplinary team
      care. Exercises involving simulation of disability were largely acceptable. We
      believe that this topic helps our students to deal better with the problems of
      disabled people.

PMID- 10964216
TI  - WFME task force on defining international standards in basic medical education.
      Report of the working party, Copenhagen, 14-16 October 1999.

PMID- 10964217
TI  - Explanatory style and the performance of residents.
AB  - PURPOSE: Explanatory (i.e. attributional) style has been shown to be related to
      performance, especially when attributions are pessimistic. This study tested
      whether this relationship was present for residents. METHOD: The Attributional
      Style Questionnaire and the Brief Symptom Inventory were completed by 45
      residents. Clinical rotation evaluations and in-training examination scores were
      used as performance measures. RESULTS: Explanatory style and emotional distress
      were not related to performance, although explanatory style was correlated with
      emotional distress. Overall, residents displayed an optimistic explanatory style.
      CONCLUSION: The absence of a relationship between explanatory style and
      performance may be due to the tendency for this resident sample to be optimistic.
      Also, common indicators of residency performance may not accurately measure
      clinical and academic performance.

PMID- 10964218
TI  - Contraception: a new practical learning package.
AB  - BACKGROUND: A new self-directed learning package was developed to assist medical
      students learn the counselling and practical skills to enable them to communicate
      with men and women about contraception and related matters. OBJECTIVES: This
      paper describes the package and the way it was facilitated, the students' ratings
      of the package and their feedback about the session on the first time it was
      presented at four teaching hospitals. RESULTS: The students rated the
      contraception package as average. The reasons given were: no introduction to the
      contraception session, lack of a trained person to conduct and facilitate the
      contraception learning session, poor organization at one of the hospitals and too
      little emphasis on self-assessment. The assumption that the students had a basic
      hormonal knowledge prior to the contraception sessions was incorrect. DISCUSSION:
      The results suggest the contraception learning package needs a person with
      contraceptive knowledge, patient-doctor skills and experience with self-directed
      learning to be present throughout the 3-hour session and for tools to be
      available that emphasize self-assessment during the session. OUTCOME: The
      modifications to be made to the learning package include pairing male and female
      students, a reduction in duration of the learning stations, an additional
      learning station relating to hormonal contraception, and inclusion of pregnancy
      and ovulation testing. These modifications were suggested by the participating
      students.

PMID- 10964219
TI  - Teaching the teachers.

PMID- 10964220
TI  - How medical students use world wide web resources at a German medical school.

PMID- 10964221
TI  - Genetic compatibility, mate choice and patterns of parentage: invited review.
AB  - There is growing interest in the possibility that genetic compatibility may drive
      mate choice, including gamete choice, particularly from the perspective of
      understanding why females frequently mate with more than one male. Mate choice
      for compatibility differs from other forms of choice for genetic benefits (such
      as 'good genes') because individuals are expected to differ in their mate
      preferences, changing the evolutionary dynamics of sexual selection. Recent
      experiments designed to investigate genetic benefits of polyandry suggest that
      mate choice on the basis of genetic compatibility may be widespread. However, in
      most systems the mechanisms responsible for variation in compatibility are
      unknown. We review potential sources of variation in genetic compatibility and
      whether there is any evidence for mate choice driven by these factors. Selfish
      genetic elements appear to have the potential to drive mate compatibility mate
      choice, though as yet there is only one convincing example. There is abundant
      evidence for assortative mating between populations in hybrid zones, but very few
      examples where this is clearly a result of selection against mating with
      genetically less compatible individuals. There are also numerous cases of
      inbreeding avoidance, but little evidence that mate choice or differential
      fertilization success driven by genetic compatibility occurs between unrelated
      individuals. The exceptions to this are a handful of situations where both the
      alleles causing incompatibility and the alleles involved in mate choice are
      located in a chromosome region where recombination is suppressed. As yet there
      are only a few potential sources of genetic compatibility which have clearly been
      shown to drive mate choice. This may reflect limitations in the potential for the
      evolution of mate choice for genetic compatibility within populations, although
      the most promising sources of such incompatibilities have received relatively
      little research.

PMID- 10964222
TI  - Phylogenetic divergence in leatherside chub (Gila copei) inferred from
      mitochondrial cytochrome b sequences.
AB  - We examined intra-specific phylogenetic relationships in leatherside chub, Gila
      copei. The complete mitochondrial (mt) cytochrome b gene (1140 bp) was sequenced
      for 30 individuals from 10 populations that span the geographical distribution of
      this species. Traditional phylogenetic analyses revealed two deeply divergent and
      evolutionarily distinct mtDNA clades that are geographically separated in
      northern and southern drainage basins. Interpopulation sequence variation between
      clades ranged from 7.7 to 8.1%. The northern clade was genetically more similar
      and phylogenetically more closely related to the selected out-group Lepidomeda m.
      mollispinus than to the southern clade, suggesting that the taxonomy of this
      species may require revision. Sequence variation among populations within clades
      ranged from 0 to 0.3% in the north and from 0 to 0.7% in the south. Statistical
      parsimony was used to construct phylogenetic networks of haplotypes within
      clades. Nested clade analysis revealed that geographical fragmentation has played
      an important role in genetic structuring within northern and southern clades.

PMID- 10964223
TI  - Comparison of microsatellites and amplified fragment length polymorphism markers
      for parentage analysis.
AB  - This study compares the properties of dominant markers, such as amplified
      fragment length polymorphisms (AFLPs), with those of codominant multiallelic
      markers, such as microsatellites, in reconstructing parentage. These two types of
      markers were used to search for both parents of an individual without prior
      knowledge of their relationships, by calculating likelihood ratios based on
      genotypic data, including mistyping. Experimental data on 89 oak trees genotyped
      for six microsatellite markers and 159 polymorphic AFLP loci were used as a
      starting point for simulations and tests. Both sets of markers produced high
      exclusion probabilities, and among dominant markers those with dominant allele
      frequencies in the range 0.1-0.4 were more informative. Such codominant and
      dominant markers can be used to construct powerful statistical tests to decide
      whether a genotyped individual (or two individuals) can be considered as the true
      parent (or parent pair). Gene flow from outside the study stand (GFO), inferred
      from parentage analysis with microsatellites, overestimated the true GFO, whereas
      with AFLPs it was underestimated. As expected, dominant markers are less
      efficient than codominant markers for achieving this, but can still be used with
      good confidence, especially when loci are deliberately selected according to
      their allele frequencies.

PMID- 10964224
TI  - Phylogeography, intraspecific structure and sex-biased dispersal of Dall's
      porpoise, Phocoenoides dalli, revealed by mitochondrial and microsatellite DNA
      analyses.
AB  - Mitochondrial DNA (mtDNA) control-region sequences and microsatellite loci length
      polymorphisms were used to estimate phylogeographical patterns (historical
      patterns underlying contemporary distribution), intraspecific population
      structure and gender-biased dispersal of Phocoenoides dalli dalli across its
      entire range. One-hundred and thirteen animals from several geographical strata
      were sequenced over 379 bp of mtDNA, resulting in 58 mtDNA haplotypes. Analysis
      using F(ST) values (based on haplotype frequencies) and phi(ST) values (based on
      frequencies and genetic distances between haplotypes) yielded statistically
      significant separation (bootstrap values P < 0.05) among most of the stocks
      currently used for management purposes. A minimum spanning network of haplotypes
      showed two very distinctive clusters, differentially occupied by western and
      eastern populations, with some common widespread haplotypes. This suggests some
      degree of phyletic radiation from west to east, superimposed on gene flow. Highly
      male-biased migration was detected for several population comparisons. Nuclear
      microsatellite DNA markers (119 individuals and six loci) provided additional
      support for population subdivision and gender-biased dispersal detected in the
      mtDNA sequences. Analysis using F(ST) values (based on allelic frequencies)
      yielded statistically significant separation between some, but not all,
      populations distinguished by mtDNA analysis. R(ST) values (based on frequencies
      of and genetic distance between alleles) showed no statistically significant
      subdivision. Again, highly male-biased dispersal was detected for all population
      comparisons, suggesting, together with morphological and reproductive data, the
      existence of sexual selection. Our molecular results argue for nine distinct
      dalli-type populations that should be treated as separate units for management
      purposes.

PMID- 10964225
TI  - Mitochondrial DNA evolution and population history of the Tenerife skink
      Chalcides viridanus.
AB  - Recent studies of island lizards have suggested that historical vicariance as a
      result of volcanism may have played an important role in shaping patterns of
      within-island genetic diversity. The skink, Chalcides viridanus, shows variation
      in morphology within the volcanic island of Tenerife. Two mitochondrial DNA
      (mtDNA) fragments (from the 12S and 16S rRNA regions) were sequenced in
      individuals from 17 sites to evaluate the relationship between current
      phylogeography and the geological history of the island. Three main clades were
      detected. The two most basal clades were restricted to areas representing the
      ancient precursor islands of Teno and Anaga in the northwest and northeast of
      Tenerife, respectively. The third clade showed a widespread geographical
      distribution and provided evidence of a recent rapid expansion after a
      bottleneck. Within-island cladogenesis appears to have taken place during a
      recent period of volcanic activity and long after the ancient islands had been
      united by the eruptions that led to the formation of the Canadas edifice.
      Evidence of similar biogeographical histories are found in other species in the
      Canary archipelago, supporting the volcanism scenario as a potentially widespread
      cause of within-island differentiation in reptiles.

PMID- 10964226
TI  - Genetic evidence for host specificity in the hemi-parasitic Viscum album L.
      (Viscaceae).
AB  - Nuclear ribosomal DNA (nrDNA) ITS sequences and partial sequences of three non
      coding chloroplast DNA (cpDNA) introns and spacers were used to assess genetic
      variation within and among three presumed host races of the hemi-parasite Viscum
      album L. Currently, identification of host races occurs via the host trees, and
      morphological differences are minute at best. cpDNA and nrDNA ITS sequences
      revealed little sequence variation, but the variation found consistently
      supported the distinction of three host races. cpDNA and ITS sequences were not
      incongruent, as assessed by the incongruence length difference test. A combined
      analysis supported the sister group relationship between mistletoes from
      deciduous trees and fir.

PMID- 10964227
TI  - Microsatellite variation in Daphnia pulex from both sides of the Baltic Sea.
AB  - Despite large genetic differentiation among neighbouring populations of many
      freshwater zooplankton species, a macrogeographical homogeneity of allozyme
      variation is generally observed. A study on breeding systems in Scandinavian
      populations of Daphnia pulex suggested a latitudinally related cline in breeding
      system with both diploid cyclic parthenogens and diploid obligate parthenogens at
      the latitude of 60-61 degrees N. Variation at neutral markers may be more
      affected by selection at linked loci in such species than in strictly sexual
      species. In this paper I present a study of variation at five microsatellite loci
      in a total of 34 populations from small ponds and rockpools on both sides of the
      Baltic Sea at 60-61 degrees N. Two major groups, which may represent different
      species of the D. pulex complex, are defined with the microsatellites.
      Neighbouring populations show both similar and well differentiated genetic
      composition. Populations separated by larger geographical distances show only a
      large differentiation and a macrogeographic pattern. The large differentiation
      observed at small distances can be explained with small effective population
      size: variation at the microsatellite loci has been shaped by population
      bottlenecks followed with expansion in size, and possibly by selection. No
      conclusive evidence is found for obligative parthenogenesis.

PMID- 10964228
TI  - Spatial and temporal distribution of chloroplast DNA polymorphism in a tropical
      tree species.
AB  - The level and the spatial organization of chloroplast DNA polymorphism were
      investigated in Dicorynia guianensis Hamshoff (Caesalpiniaceae) at different
      spatial and temporal scales. D. guianensis is a canopy tree of the rain forest
      that is distributed throughout the Guiana plateau in small aggregates. Twelve
      different haplotypes were identified using restriction analysis of polymerase
      chain reaction (PCR) amplified fragments of the chloroplast genome. When
      populations from different areas of French Guiana were compared, a clear
      geographical pattern of haplotype frequencies was identified along the Atlantic
      coast. This pattern is most likely the result of the restriction-expansion
      dynamics of the tropical forest during the Quaternary. At the local level, D.
      guianensis was characterized by a high level of within population diversity.
      Maintenance of within population diversity results from the dynamics of the
      aggregates; stochastic demography associated with the turnover of aggregates
      generates genetic differentiation among them. At the stand level, a strong
      spatial aggregation of haplotypes persisted from the adult to the seedling cohort
      indicating limited seed flow. There was also a strong difference in levels of
      diversity between the cohorts which suggested that recruitment over several years
      is needed in order to maintain genetic diversity during regeneration.

PMID- 10964229
TI  - Dynamics of genotypic structure in clonal Rhododendron ferrugineum (Ericaceae)
      populations.
AB  - Two populations of Rhododendron ferrugineum growing at subalpine level in the
      Pyrenees (France) were studied in two sites (Bethmale and Mourtis).
      Identification and delimitation of genets were inferred from amplified fragment
      length polymorphism (AFLP) markers, along a closure gradient (from meadow to more
      closed heath) in each site. Surface and age of genets, genotypic diversity
      (Simpson's index D), 'proportion distinguishable' genotypes and genetic
      relationships between genets were then estimated. Amplification of the 312 DNA
      samples with three selective primer pairs gave a mean of 98 detectable peaks
      (i.e. bands) per sample, with size ranging from 60 to 300 bp. In total 60%
      (Bethmale) and 70% (Mourtis) of the peaks were polymorphic, and a total of 31 and
      23 multilocus genotypes were identified, in Bethmale and Mourtis, respectively.
      We inferred that pioneer genotypes began arriving 110 years ago mainly over a 40
      year period in the Mourtis meadow, and began about 130 years ago over a 100-year
      period in the Bethmale meadow. After this pioneer stage, populations extended
      vegetatively. Two different patterns of genotypic dynamics can be identified. At
      Bethmale, population closure could have led to a dramatic loss of genets and to
      the selection of highly genetically related genotypes. In contrast, at Mourtis,
      genotypic diversity and genet density did not change fundamentally along the
      closure gradient. However the range of genetic diversity diminished from the open
      to the closed situation, suggesting that thinning could have occurred in the
      past.

PMID- 10964230
TI  - Chloroplast DNA haplotype variation and population differentiation in Sorbus
      aucuparia L. (Rosaceae: Maloideae).
AB  - Intra-specific chloroplast DNA (cpDNA) variation was studied in Sorbus aucuparia
      L., an entomophilous, mid-or early successional tree producing fleshy fruits.
      Eight PCR-amplified fragments of the chloroplast genome were screened for
      restriction fragment length polymorphisms, using one or two 4 bp-cutter
      restriction endonucleases. cpDNA variation was investigated on two geographical
      scales: (1) among four regions in France and Belgium; and (2) within the Belgian
      region. A total of 150 individuals from six populations were analysed. Fourteen
      polymorphisms were detected in six of the cpDNA fragments. All polymorphisms
      probably resulted from insertions or deletions, and allowed the identification of
      12 haplotypes. The level of genetic differentiation computed on the basis of
      haplotype frequencies was similar on the two geographical scales considered
      (G(STc) = 0.286 among regions, G(STc) = 0.259 among populations within the
      Belgian region). These values are much lower than those obtained in nine
      previously studied temperate tree species, which are all wind-pollinated, late
      successional species producing dry fruits. These results might primarily be
      accounted for by the contrasting life history traits of S. aucuparia. In order to
      obtain insights into the relative contribution of pollen and seeds to gene flow,
      G(STc) was also compared with previously obtained G(ST) estimates based on
      allozyme data.

PMID- 10964232
TI  - Genetic variation and population structure in the endangered greater horseshoe
      bat Rhinolophus ferrumequinum.
AB  - Following a dramatic decline last century, the British population of the
      endangered greater horseshoe bat Rhinolophus ferrumequinum is highly fragmented.
      To examine the consequences of fragmentation and limited dispersal on patterns of
      genetic structure and variation, we used microsatellite markers to screen bats
      from around 50% of the known maternity colonies in Britain, and two areas from
      continental Europe. Analyses revealed that Welsh and English colonies were
      genetically isolated. This, and lower variability in Britain than north France,
      may result from either genetic drift, or the species' colonization history. Gene
      flow among most neighbouring colonies was not generally restricted, with one
      exception. These findings have important implications for the ongoing
      conservation management of this species.

PMID- 10964231
TI  - Offspring sex ratios in tree swallows: females in better condition produce more
      sons.
AB  - Organisms are expected to adjust the sex ratio of their offspring in relation to
      the relative fitness benefits of sons and daughters. We used a molecular sexing
      technique that amplifies an intron of the CHD1 gene in birds to examine the sex
      ratio at egg-laying in socially monogamous tree swallows (Tachycineta bicolor).
      We examined all individuals in 40 broods (210 young), including all unhatched
      eggs and nestlings. Thus, the sex ratio we measured was the same as the sex ratio
      at laying. Overall, the mean sex ratio per brood (+/- SD) was biased
      significantly towards males (57 +/- 2% male). Within broods, male-biased sex
      ratios were associated with females in better body condition, and these females
      were more likely to produce sons in better condition. Tree swallows have one of
      the highest known levels of extra-pair paternity in birds (38-76% extra-pair
      young), and, as a consequence, variance in male reproductive success is greater
      than that of females. Thus, in tree swallows, investment in sons has the
      potential for higher fitness returns than investment in daughters, assuming that
      sons in better condition have greater reproductive success.

PMID- 10964233
TI  - Discrepancies in population differentiation at microsatellites, mitochondrial DNA
      and plumage colour in the pied flycatcher--inferring evolutionary processes.
AB  - Genetic differentiation between three populations of the pied flycatcher Ficedula
      hypoleuca (Norway, Czech Republic and Spain, respectively) was investigated at
      microsatellite loci and mitochondrial DNA (mtDNA) sequences and compared with the
      pattern of differentiation of male plumage colour. The Czech population lives
      sympatrically with the closely related collared flycatcher (F. albicollis)
      whereas the other two are allopatric. Allopatric populations are on average more
      conspicuously coloured than sympatric ones, a pattern that has been explained by
      sexual selection for conspicuous colour in allopatry and a character displacement
      on breeding plumage colour in sympatry that reduces the rate of hybridization
      with the collared flycatcher. The Czech population was genetically
      indistinguishable from the Norwegian population at microsatellite loci and mtDNA
      sequences. Recent isolation and/or gene flow may explain the lack of genetic
      differentiation. Accordingly, different selection on plumage colour in the two
      populations is either sufficiently strong so that gene flow has little impact on
      the pattern of colour variation, or differentiation of plumage colour occurred so
      recently that the (presumably) neutral, fast evolving markers employed here are
      unable to reflect the differentiation. Genetically, the Spanish population was
      significantly differentiated from the other populations, but the divergence was
      much more pronounced at mtDNA compared to microsatellites. This may reflect
      increased rate of differentiation by genetic drift at the mitochondrial, compared
      with the nuclear genome, caused by the smaller effective population size of the
      former genome. In accordance with this interpretation, a genetic pattern
      consistent with effects of small population size in the Spanish population
      (genetic drift and inbreeding) were also apparent at the microsatellites, namely
      reduced allelic diversity and heterozygous deficiency.

PMID- 10964234
TI  - Genetic analysis and conservation of 31 surviving individuals of a rare New
      Zealand tree, Metrosideros bartlettii (Myrtaceae).
AB  - Metrosideros bartlettii (Myrtaceae) is a distinctive and extremely rare tree,
      endemic to New Zealand, first discovered in 1975. Prior to this study, a total of
      19 adult individuals of the species had been reported; these are located in three
      small forest remnants in the far north of the North Island of New Zealand. Here
      we describe a total of 31 adult M. bartlettii at the three sites, including 12
      individuals newly discovered by us. We analyse the genetic diversity of the
      species, using microsatellites to examine the chloroplast genome and amplified
      fragment length polymorphisms (AFLPs) to monitor nuclear variation. The results
      clearly demonstrate that M. bartlettii is a unique species, distinct from its two
      closest relatives M. robusta and M. excelsa. Analysis of genetic diversity within
      the 31 remaining individuals of M. bartlettii showed an average heterozygosity (<
      H >) of 0.18 and a proportion of polymorphic genes (< P >) of 0.44. Population
      structure, as shown by 286 AFLP loci, varied between the three geographical
      sites; the site with fewest individuals, containing two trees, showed some
      separation from the populations at the other two locations. These two latter
      sites, by contrast, had highly overlapping AFLP population diversity profiles.
      The implications of these results for conservation of the species are discussed.

PMID- 10964235
TI  - Higher impact of female than male migration on population structure in large
      mammals.
AB  - We simulated large mammal populations using an individual-based stochastic model
      under various sex-specific migration schemes and life history parameters from the
      blue whale and the Asian elephant. Our model predicts that genetic structure at
      nuclear loci is significantly more influenced by female than by male migration.
      We identified requisite comigration of mother and offspring during gravidity and
      lactation as the primary cause of this phenomenon. In addition, our model
      predicts that the common assumption that geographical patterns of mitochondrial
      DNA (mtDNA) could be translated into female migration rates (Nmf) will cause
      biased estimates of maternal gene flow when extensive male migration occurs and
      male mtDNA haplotypes are included in the analysis.

PMID- 10964236
TI  - Population subdivision in Europe's great bustard inferred from mitochondrial and
      nuclear DNA sequence variation.
AB  - A continent-wide survey of sequence variation in mitochondrial (mt) and nuclear
      (n) DNA of the endangered great bustard (Otis tarda) was conducted to assess the
      extent of phylogeographic structure in a morphologically monotypic bird. DNA
      sequence variation in a combined 809 bp segment of the mtDNA genome from 66
      individuals from the last six breeding regions showed relatively low levels of
      intraspecific sequence diversity (n = 0.32%) but significant differences in the
      regional distribution of 11 haplotypes (phiST = 0.49). Despite their exceptional
      potential for dispersal, a complete and long-term historical separation between
      the populations from the Iberian Peninsula (Spain) and mainland Europe (Hungary,
      Slovakia, Germany, and Russia) was demonstrated. Divergence between populations
      based on a 3-bp insertion-deletion polymorphism within the intron region of the
      nuclear CHD-Z gene was geographically concordant with the primary subdivision
      identified within the mtDNA sequences. Inferred aspects of phylogeography were
      used to formulate conservation recommendations for this endangered species.

PMID- 10964237
TI  - Identification of microsatellite loci in olive (Olea europaea) and their
      characaterization in Italian and Iberian olive trees.

PMID- 10964238
TI  - Polymerase chain reaction primers for microsatellite loci in the north European
      water frogs Rana ridibunda and R. lessonae.

PMID- 10964239
TI  - Microsatellite primers and amplification of aborted embryos in Platypodium
      elegans J. Vogel (Fabaceae, Papilionoideae).

PMID- 10964241
TI  - Characterization of microsatellite loci in Coffea arabica and related coffee
      species.

PMID- 10964240
TI  - Isolation and characterization of dinucleotide microsatellite loci in the Great
      White Shark, Carcharodon carcharias.

PMID- 10964242
TI  - Microsatellite loci from the marine fish Nemadactylus macropterus (Perciformes:
      Cheilodactylidae).

PMID- 10964243
TI  - Isolation and characterization of microsatellite loci from the human whipworm
      Trichuris trichiura.

PMID- 10964244
TI  - Characterization of microsatellite loci in the Australian Blacklip abalone
      (Haliotis rubra, Leach).

PMID- 10964245
TI  - Highly polymorphic microsatellite loci in the Heron Reef population of the
      tropical abalone Haliotis asinina.

PMID- 10964246
TI  - Isolation and characterization of microsatellite loci from the Japanese red pine,
      Pinus densiflora.

PMID- 10964247
TI  - PRIMER NOTES: Isolation of microsatellite markers in Castanopsis cuspidata var.
      sieboldii Nakai from an enriched library.

PMID- 10964248
TI  - Microsatellite markers for the ectomycorrhizal basidiomycete Rhizopogon
      vinicolor.

PMID- 10964249
TI  - Highly polymorphic microsatellite markers in the landsnail Helix aspersa
      (Mollusca Gastropoda).

PMID- 10964250
TI  - Feeding DHEA to C57/B167 mice.

PMID- 10964251
TI  - Feeding DHEA to C57/B167 mice: the authors respond

PMID- 10964252
TI  - Introduction: Forum on Responsible Conduct in Biomedical Research.

PMID- 10964253
TI  - Ethics in research.

PMID- 10964254
TI  - The evolution of the "scientific misconduct" issue: An historical overview.

PMID- 10964255
TI  - Scientific societies as sentinels of responsible research conduct.

PMID- 10964256
TI  - Scientific misconduct and research integrity for the bench scientist.
AB  - This paper describes the role of the Office of Research Integrity (ORI), a
      component of the Public Health Service (PHS), in defining scientific misconduct
      in research supported with PHS funds and in establishing standards for responding
      to allegations of misconduct. The principal methods by which ORI exercises its
      responsibilities in this area are defining what types of behaviors undertaken by
      research investigators constitute misconduct, overseeing institutional efforts to
      investigate and report misconduct, and recommending to the Assistant Secretary
      for Health (ASH) PHS administrative actions when misconduct is identified. ORI
      also takes affirmative steps to promote research integrity through education,
      training, and other initiatives. The role of the research institution in
      responding to misconduct and promoting research integrity is complementary and
      overlapping with ORI's efforts but, as the employer of research investigators and
      front-line manager of the research, the institution has a greater opportunity to
      promote the highest standards of integrity in the day-to-day conduct of research.
      Finally, legal precedent established through civil litigation has played an
      important role in defining the standards that apply in determining when a breach
      of research integrity has occurred.

PMID- 10964257
TI  - Host immune response to intracellular bacteria: A role for MHC-linked class-Ib
      antigen-presenting molecules.
AB  - MHC-linked class-Ib molecules are a subfamily of class-I molecules that display
      limited genetic polymorphism. At one time these molecules were considered to have
      an enigmatic function. However, recent studies have shown that MHC-linked class
      Ib molecules can function as antigen presentation structures that bind bacteria
      derived epitopes for recognition by CD8+ effector T cells. This role for class-Ib
      molecules has been demonstrated across broad classes of intracellular bacteria
      including Listeria moncytogenes, Salmonella typhimurium, and Mycobacterium
      tuberculosis. Additionally, evidence is emerging that MHC-linked class-Ib
      molecules also serve an integral role as recognition elements for NK cells as
      well as several TCR alpha/beta and TCR gamma/delta T-cell subsets. Thus, MHC
      linked class-Ib molecules contribute to the host immune response by serving as
      antigen presentation molecules and recognition ligands in both the innate and
      adaptive immune response to infection. In this review, we will attempt to
      summarize the work that supports a role for MHC-linked class-Ib molecules in the
      host response to infection with intracellular bacteria.

PMID- 10964258
TI  - Advances in livestock nuclear transfer.
AB  - Cloning and transgenic animal production have been greatly enhanced by the
      development of nuclear transfer technology. In the past, genetic modification in
      domestic animals was not tightly controlled. With the nuclear transfer technology
      one can now create some domestic animals with specific genetic modifications. An
      ever-expanding variety of cell types have been successfully used as donors to
      create the clones. Both cell fusion and microinjection are successfully being
      used to create these animals. However, it is still not clear which stage(s) of
      the cell cycle for donor and recipient cells yield the greatest degree of
      development. While for the most part gene expression is reprogrammed in nuclear
      transfer embryos, all structural changes may not be corrected as evidenced by the
      length of the telomeres in sheep resulting from nuclear transfer. Even after
      these animals are created the question of "are they really clones?" arises due to
      mitochondrial inheritance from the donor cell versus the recipient oocyte. This
      review discusses these issues as they relate to livestock.

PMID- 10964259
TI  - Thiamine intestinal transport and related issues: recent aspects.
AB  - In the intestinal lumen thiamine is in free form and very low concentrations.
      Absorption takes place primarily in the proximal part of the small intestine by
      means of a dual mechanism, which is saturable at low (physiological)
      concentrations and diffusive at higher. Thiamine undergoes intracellular
      phosphorylation mainly to thiamine pyrophosphate, while at the serosal side only
      free thiamine is present. Thiamine uptake is enhanced by thiamine deficiency, and
      reduced by thyroid hormone and diabetes. The entry of thiamine into the
      enterocyte, as evaluated in brush border membrane vesicles of rat small intestine
      in the absence of H+ gradient, is Na+- and biotransformation-independent,
      completely inhibited by thiamine analogs and reduced by ethanol administration
      and aging. The transport involves a saturable mechanism at low concentrations of
      vitamin and simple diffusion at higher. Outwardly oriented H+ gradients enhance
      thiamine transport, whose saturable component is a Na+-independent electroneutral
      uphill process utilizing energy supplied by the H+ gradient, and involving a
      thiamine/ H+ 1:1 stoichiometric exchange. The exit of thiamine from the
      enterocyte, as evaluated in basolateral membrane vesicles, is Na+-dependent,
      directly coupled to ATP hydrolysis by Na+-K+-ATPase, and inhibited by thiamine
      analogs. Transport of thiamine by renal brush border membrane vesicles is similar
      to the intestinal as far as both H+ gradient influence and specificity are
      concerned. In the erythrocyte thiamine transport is a Na+-independent,
      electroneutral process yet with two components: saturable, prevailing at low
      thiamine concentrations, and diffusive at higher. The saturable (specific)
      component is missing in patients of the rare disease known as thiamine-responsive
      megaloblastic anaemia (TRMA), producing a general disturbance of thiamine
      transport up to thiamine deficiency. The TRMA gene is located in chromosome
      1q23.3. Recently, the thiamine transporter has been cloned: it is a protein of
      497 amino acid residues with high homology with the reduced-folate transporter.

PMID- 10964260
TI  - Low-protein diet changes thyroid function in lactating rats.
AB  - Lactating rats were fed with free access to an 8% protein-restricted diet (PR);
      the control group was fed a 23% protein diet (C). An energy-restricted (pair-fed)
      group was given the same food as the animals in the control group, but the
      amounts of food consumed by both PF and PR were about the same. The body weight
      and serum albumin concentration of PR and PF dams were significantly (P < 0. 05)
      lower than that of the controls. The PR group had a significant increase in serum
      free triiodothyronine (FT3) concentration, 24-hr mammary gland and milk
      radioiodine (I131) uptake (67%, 278%, and 200%, respectively) as compared with
      the controls. On the other hand, those animals had a significantly lower serum
      free thyroxine (FT4) concentration and 2- and 24-hr thyroid I131 uptake (67%,
      64%, and 74%, respectively). Protein malnutrition during lactation did not alter
      thyroid or liver 5'-deiodinase activity significantly. However, PF dams had a
      significantly lower (25%) thyroid 5'-deiodinase activity. These data suggest that
      protein-restricted lactating dams had an adaptive change in the thyroid function,
      which could be important to increase the transference of iodine or
      triiodothyronine through the milk to their pups and prevent sequelae of neonatal
      hypothyroidism.

PMID- 10964261
TI  - Detection of antigen-specific human serum proteins related to the T-cell receptor
      in infectious disease and in an immune response to milk proteins or chemicals.
AB  - A monoclonal IgG2 antibody, MG3C9-1 A12, was prepared by immunization of mice
      with human serum Cohn Fraction III proteins enriched for TCR Ca+ proteins. MG3C9
      1 A12 bound to Mr 28,000, antigen-specific TCR Ca+, beta-, and TCR Ca+, beta+
      serum proteins associated with TGF-beta1, 2. The IgG2 monoclonal antibody also
      bound to T-lymphocyte proteins but did not bind to B lymphocyte proteins, human
      albumin, IgM, IgG, IgA, or TGF-beta1, 2, 3 immunogenic peptides. Monoclonal MG3C9
      1 A12 detected TCR-related proteins specific for filarial extract, milk proteins,
      or benzoic acid in the sera of individuals with chronic or asymptomatic
      filariasis, milk intolerance, or sensitivity to toluene, respectively. TCR
      related serum proteins were also detected intracellularly in mononuclear cells in
      frozen sections of ileum from a patient with milk intolerance and reactive
      mesenteric lymph nodes from a patient with a gastric ulcer. The results suggest
      that antigen-specific TCR-related serum proteins may be elevated during an immune
      response to oral, environmental, or infectious stimuli.

PMID- 10964262
TI  - Age-related changes in plasma leptin binding activity in rats: A comparison of a
      simple acid-ethanol precipitation technique with column chromatography.
AB  - A novel assay for measuring the free leptin fraction was developed and validated
      against a chromatographic technique. The assay used acid-ethanol extraction (AEE)
      for separation of bound/free leptin moieties. The interassay coefficient of
      variation was 3.9%. The specificity for leptin binding was confirmed by
      incubation with 1 microg of unlabeled rat leptin that effectively competed with
      radiolabeled leptin whereas human growth hormone and interleukin-6 were
      ineffective in competing with radiolabeled leptin binding. Scatchard analysis of
      competitive binding experiments with rat plasma demonstrated a linear
      relationship with a binding affinity of 0.3-0.6 x 109 M-1. This novel assay was
      used to determine if age-related insensitivity to leptin action is secondary to
      altered serum leptin binding. Rats at various age groups were studied for changes
      in body adiposity and serum total and free leptin concentrations. Serum free
      leptin concentrations (ng/ml mean +/- SEM) were significantly increased in 24
      month-old rats (5.56 +/- 0. 21) compared with 18-month-old rats (4.76 +/- 0.17)
      (P < 0.01) despite similar body weight and adiposity of the two age groups. The
      increase in plasma free leptin concentrations in 12-month-old rats (3.86 +/-
      0.28) and 6-month-old rats (2.05 +/- 0.06) relative to 3-month-old rats (1.37 +/-
      0.06) (P < 0.001) was out of proportion to the increase in body adiposity in
      aging rats. It is concluded that aging in rats is associated with relative
      insensitivity to leptin. This change cannot be attributed to increased plasma
      binding or to a reduction in the leptin free fraction.

PMID- 10964263
TI  - Characterization of serum dehydroepiandrosterone secretion in golden hamsters.
AB  - Dehydroepiandrosterone (DHEA) is an adrenal androgen whose function is poorly
      understood. Although DHEA and DHEA sulfate (DHEAS) are secreted in relatively
      high quantities by the human adrenal, the laboratory rat secretes very little,
      thus hindering experimental studies of the hormone. In this paper, we measured
      the changes in serum DHEA and DHEAS under various physiological conditions in
      golden hamsters. Evening serum DHEAS fell from 6.30 +/- 0.78 microg/dl (mean +/-
      SE) before surgery to 3.03 +/- 0.23 microg/dl 12 days after bilateral
      adrenalectomy. Hamsters had higher levels of DHEA and DHEAS in the evening than
      in the morning, but removal of the gonads did not consistently decrease serum
      DHEA or DHEAS in males or females. Evening levels of DHEA and DHEAS reached a
      peak around 7 weeks of age and then gradually decreased to about one-third of
      these levels by one year of age. These results suggest that DHEA and DHEAS are
      secreted at least in part from the hamster adrenal, that they do not originate
      from the gonads, and that there is a daily rhythm with peak levels at a time of
      day just preceding the active phase. In addition, the levels of these hormones
      decrease with aging.

PMID- 10964264
TI  - Ovarian steroidogenic responsiveness to exogenous gonadotropin stimulation in
      young and middle-aged female rats.
AB  - Reproductive aging in the female rat is associated with gradual declines in LH
      secretion and ovarian progesterone (P) production. This study examined whether
      the influences of aging on P levels reflect decreased ovarian responsiveness to
      gonadotropin stimulation, as opposed to changes in gonadotropin release. Young
      and middle-aged regularly cyclic female rats received sodium pentobarbital to
      block endogenous proestrous luteinizing hormone (LH) surges, followed by
      administration of various doses of human chorionic gonadotropin (hCG). Similar
      treatments were performed in middle-aged acyclic persistent-estrous (PE) females.
      Injection of hCG resulted in equivalent plasma hCG levels in each treatment
      group. At the lowest hCG dose tested, a significant rise in plasma P levels was
      observed in middle-aged cyclic rats, but not in young cyclic or middle-aged PE
      females. This unexpected finding may reflect accelerated follicular development
      in middle-aged cyclic females, as suggested by a previous study. At the
      intermediate dose, young and middle-aged cyclic but not PE rats displayed
      significantly increased P in response to hCG. At the highest dose tested, all
      three groups of rats displayed increased P levels after hCG stimulation. However,
      P concentrations were significantly lower in middle-aged PE than regularly cyclic
      females. Northern and slot blot hybridization analyses revealed that ovarian mRNA
      levels for cytochrome P450 side-chain cleavage, the rate-limiting enzyme in P
      synthesis, were markedly reduced in PE rats following hCG stimulation. These
      findings indicate that ovarian responsiveness to gonadotropin stimulation is
      impaired in middle-aged PE, but not regularly cyclic rats, and suggest influences
      of cycle status on the biochemical and molecular mechanisms regulating ovarian
      steroid production. Furthermore, these findings reveal that attenuated P
      production in middle-aged proestrous rats is due to attenuated preovulatory LH
      surges, rather than decreased ovarian sensitivity to LH.

PMID- 10964265
TI  - Antiproliferative and apoptotic effects of tocopherols and tocotrienols on
      preneoplastic and neoplastic mouse mammary epithelial cells.
AB  - Studies were conducted to determine the comparative effects of tocopherols and
      tocotrienols on preneoplastic (CL-S1), neoplastic (-SA), and highly malignant
      (+SA) mouse mammary epithelial cell growth and viability in vitro. Over a 5-day
      culture period, treatment with 0-120 microM alpha- and gamma-tocopherol had no
      effect on cell proliferation, whereas growth was inhibited 50% (IC50) as compared
      with controls by treatment with the following: 13, 7, and 6 microM tocotrienol
      rich-fraction of palm oil (TRF); 55, 47, and 23 microM delta-tocopherol; 12, 7,
      and 5 microM alpha-tocotrienol; 8, 5, and 4 microM gamma-tocotrienol; or 7, 4,
      and 3 microM delta-tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute
      24-hr exposure to 0-250 microM alpha- or gamma-tocopherol (CL-S1, -SA, and +SA)
      or 0-250 microM delta-tocopherol (CL-S1) had no effect on cell viability, whereas
      cell viability was reduced 50% (LD50) as compared with controls by treatment with
      166 or 125 microM delta-tocopherol in -SA and +SA cells, respectively. Additional
      LD50 doses were determined as the following: 50, 43, and 38 microM TRF; 27, 28,
      and 23 microM alpha-tocotrienol; 19, 17, and 14 microM gamma-tocotrienol; or 16,
      15, or 12 microM delta-tocotrienol in CL-S1, -SA, and +SA cells, respectively.
      Treatment-induced cell death resulted from activation of apoptosis, as indicated
      by DNA fragmentation. Results also showed that CL-S1, -SA, and +SA cells
      preferentially accumulate tocotrienols as compared with tocopherols, and this may
      partially explain why tocotrienols display greater biopotency than tocopherols.
      These data also showed that highly malignant +SA cells were the most sensitive,
      whereas the preneoplastic CL-S1 cells were the least sensitive to the
      antiproliferative and apoptotic effects of tocotrienols, and suggest that
      tocotrienols may have potential health benefits in preventing and/or reducing the
      risk of breast cancer in women.

PMID- 10964267
TI  - Interactions between HIV infection and other sexually transmitted diseases.
AB  - Mechanisms and implications of the interaction between HIV and other STDs such as
      syphilis, Herpes simplex, Chlamydia and Neisseria gonorrhoeae infection are
      presented and relevant case reports and trials described.

PMID- 10964268
TI  - Partnership and fragmentation in international health: threat or opportunity?

PMID- 10964266
TI  - Inhibition of ethanol-induced liver disease in the intragastric feeding rat model
      by chlormethiazole.
AB  - The purpose of this investigation was to assess the effect of chlormethiazole
      treatment on liver damage in the experimental rat intragastric ethanol-feeding
      model of alcoholic liver disease. Chlormethiazole has been used in the treatment
      of alcoholic withdrawal and has been shown to inhibit cytochrome P4502E1. Since
      treatment of experimental alcoholic liver disease with CYP2E1 inhibitors had an
      ameliorating effect on liver injury in the rat, chlormethiazole was used to see
      if it had a similar effect. Rats fed ethanol for 2 months had significantly less
      liver injury when chlormethiazole was added to the diet, fed intragastrically.
      The CYP2E1 apoprotein levels, which were increased by ethanol feeding, were also
      increased when chlormethiazole was fed with ethanol. Chlormethiazole inhibited
      the increase in the ethanol-induced CYP2E1 activity in vivo, as measured by
      chlorzoxazone 6-hydroxylation, but did not affect the level of CYP2E1 apoprotein.
      Likewise, the reduction in proteasome proteolytic enzyme activity produced by
      ethanol feeding was blunted in chlormethiazole-fed rats. These results support
      the conclusion that chlormethiazole treatment partially protects the liver from
      injury by inhibiting CYP2E1 activity in vivo.

PMID- 10964269
TI  - Indoor residual spraying with alphacypermethrin controls malaria in Pakistan: a
      community-randomized trial.
AB  - We conducted a community-randomized controlled trial in Pakistan to determine the
      efficacy of indoor residual spraying with alphacypermethrin ('Fendona', Cyanamid,
      NJ, USA), applied at 25 mg/m2, to prevent falciparum and vivax malaria. Wettable
      powder (WP) and suspension concentrate (SC) formulations were tested against an
      unsprayed control in an irrigated rice-growing area of Sheikhupura district,
      Punjab province. The study area of 180 km2 was divided into nine sectors, which
      were assigned at random to control, WP, or SC treatments in replicates of 3.
      Sentinel villages were selected from each sector for entomological and disease
      monitoring. Malaria was monitored by fortnightly active case detection (ACD) and
      by cross- sectional parasite surveys on schoolchildren. Mosquito populations were
      monitored by space spraying of rooms and by cattle-landing catches. The spray
      campaign took place in June 1997 and covered 96% of compounds. During the 7
      months after spraying, the incidence of falciparum malaria was 95% lower and that
      of vivax malaria 80% lower in WP-sprayed than unsprayed sectors. Similar results
      were obtained for sectors sprayed with the SC formulation. Cross-sectional
      surveys gave estimates of efficacy comparable to those obtained by ACD. Anopheles
      culicifacies was 80% less abundant and A.stephensi, the predominant anopheline,
      was up to 68% less abundant in sprayed areas over the 7-month period. Reductions
      in anopheline parous rates indicated that the single-spray treatment was
      effective for the entire transmission season. Sprayed surfaces lacked odour,
      which contributed to the popularity of the campaign. Alphacypermethrin is a
      promising insecticide for the control of malaria in Pakistan and South Asia
      generally.

PMID- 10964270
TI  - Pregnancy and HIV-1 incidence in 178 married couples with discordant HIV-1
      serostatus: additional experience at an HIV-1 counselling centre in the
      Democratic Republic of the Congo.
AB  - To determine the effect of an HIV-1 counselling programme on rates of HIV-1
      infection and pregnancy in a large group of married couples in Kinshasa, DRC with
      discordant HIV-1 infection status, we conducted a baseline cross-sectional HIV-1
      seroprevalence study in two large Kinshasa businesses. We identified 178 married
      couples (mean duration of marriage = 12.3 years) with discordant HIV-1 serostatus
      (92 M+F-/86 M-F+). Seroincidence and pregnancy rates were observed during 310
      person-years of follow-up (PYFU). The 92 M+F- couples had an HIV-1 incidence of
      3.7/100 PYFU and a pregnancy rate of 8.6/100. The 86 M-F+ couples had a pregnancy
      rate of 6.8/100 PYFU and an HIV-1 incidence of 6.8/100 PYFU. Couples seeking to
      have children but minimize their HIV-1 transmission risk frequently had
      unprotected sex only during the woman's perceived monthly fertility period. This
      strategy resulted in the birth of 24 live-born children and only one (4%; 95% CL
      = 0.0-21.6%) new HIV infection in couples having a child. Only 1 of 6 women who
      developed HIV-1 infection (16. 7%; 95 C.L. = 0-40.4%) became pregnant. While
      seronegative men had more extramarital sex once their wives' positive HIV-1
      infection status became known, most of these episodes involved safe sex. Divorce
      was rare. This study provides additional information concerning issues of safe
      sex in married couples with discordant HIV-1 infection status, the dynamics of
      HIV transmission within couples and the effect of serostatus notification on the
      marriage and on intramarital and extramarital sexual behaviour in Kinshasa,
      Congo.

PMID- 10964271
TI  - Genotypic patterns of multiple isolates of M. tuberculosis from tuberculous HIV
      patients.
AB  - We investigated whether the recurrence of tuberculosis in HIV-infected patients
      is due to an exogenous reinfection or relapses after antituberculosis
      chemotherapy. We reviewed clinical information on 32 patients at a Rio de Janeiro
      hospital from whom multiple Mycobacterium tuberculosis isolates were taken. All
      isolates were analysed by DRE-PCR fingerprinting technique, and those with
      identical DRE-PCR patterns were analysed by the RFLP method. Twenty patients had
      M. tuberculosis simultaneously isolated from different organs. These patients and
      nine others with sequential positive cultures after 2 months of therapy showed
      stable DRE-PCR and RFLP patterns. One patient's isolate became resistant to
      isoniazid, but the molecular pattern remained unchanged despite the development
      of drug resistance. In three patients, the DRE-PCR patterns of the isolates
      changed dramatically. Clinical and microbiological evidence was consistent with
      active tuberculosis caused by a new strain of M. tuberculosis. The exogenous
      reinfection of the three patients was not due to an outbreak, but the isolates
      from each patient showed unique patterns.

PMID- 10964272
TI  - The problem of illegally induced abortion: results from a hospital-based study
      conducted at district level in Dar es Salaam.
AB  - Illegal abortion is known to be a major contributor to maternal mortality. The
      objective of the study was firstly to identify women with illegally induced
      abortion, (IA) and to compare them with women admitted with a spontaneous
      abortion (SA) or receiving antenatal care (AC), and secondly to describe the
      circumstances which characterized the abortion. The population of this cross
      sectional questionnaire study comprised patients from Temeke District Hospital,
      Dar es Salaam, Tanzania. After an in-depth confidential interview, 603 women with
      incomplete abortion were divided into two groups: 362 women with IA and 241 with
      SA. They were compared with 307 AC women. IA women were significantly younger,
      more often better educated, unmarried, nulliparous and students than AC women.
      Regarding civil-status, educational level, proportion of nullipara and proportion
      of students, SA patients were similar to AC women. These results lend support to
      the assumption that the in-depth confidential interview made it possible to
      distinguish IA women from SA women.

PMID- 10964273
TI  - Salmonella enteritidis diarrhoea in Harare, Zimbabwe.
AB  - The study was conducted to determine the prevalence of Salmonella enteritidis
      diarrhoea in an urban area in Zimbabwe. Stool specimens from people of all ages
      presenting at primary level health centres in Harare were investigated for S.
      enteritidis and other bacterial and parasitic enteric pathogens. The first 46 S.
      enteritidis isolates were phage-typed, and all isolates were tested for
      susceptibility to ampicillin (10 microg), chloramphenicol (30 microg),
      cotrimoxazole (25 microg), tetracycline (30 microg), gentamicin (10 microg),
      nalidixic acid (30 microg), ciprofloxacin (5 microg) and ceftriaxone (30 microg).
      S. enteritidis was isolated in 74 (1.8%) of 4155 stool specimens which
      represented 30.7% of all Salmonella species isolated. The most common S.
      enteritidis phage type was 4 (78.3%) followed by 7, 9 and 23 (8.7%, 2.2%, 2.2%,
      respectively) All S. enteritidis isolates were sensitive to gentamicin,
      ciprofloxacin and ceftriaxone. Less than 10% of the isolates were resistant to
      the other antimicrobials except ampicillin, to which 13.5% were resistant. One
      isolate was resistant to ampicillin, chloramphenicol, cotrimoxazole and nalidixic
      acid.

PMID- 10964275
TI  - Daan Mulder Memorial Symposium.

PMID- 10964274
TI  - Occupational injuries with captive lance-headed vipers (Bothrops moojeni):
      experience from a snake farm in Brazil.
AB  - We studied occupational injuries with captive lance-headed vipers (Bothrops
      moojeni) that occurred in a snake farm in south-eastern Brazil from February 1981
      to May 1999. The risk of injury, taking into account 13 cases of snake-associated
      injuries (12 of them snake bites) was 2.73 per 10,000 person-days of work, and
      3.51 per 100,000 venom extractions. Thirteen cases of injury occurred in seven
      workers, whereas 18 workers were never injured, suggesting that some individuals
      have a higher risk of injury than others perhaps due to lack of concentration or
      overconfidence. Eight episodes of occupational injuries occurring in four
      technicians, including a case of eye injury due to splashed venom during
      extraction, are reported. Assessment of whether envenoming occurred was
      facilitated by knowledge of the snake species and size, history of recent venom
      extraction and snake feeding, and examination of snake venom glands.
      Hypersensitivity reactions (anaphylaxis and serum sickness) to antivenom are a
      risk particularly to those workers who were bitten more than once and medicated
      previously. Antivenom therefore should not be administered to these individuals
      unless there is clear evidence that envenoming occurred or is likely to have
      occurred. Hypersensitivity to the venom is also a health concern for workers from
      snake farms.

PMID- 10964276
TI  - The global epidemiology of HIV/AIDS.
AB  - The HIV pandemic continues to evolve, in both magnitude and diversity. In this
      paper, we briefly review the global epidemiology of HIV/AIDS, reflecting on the
      differences by region, and the challenges posed by the evolving epidemics in
      terms of prevention and surveillance. Despite the reduction in numbers of new
      AIDS cases in the US and Western Europe due to advances in treatment, a constant
      number of new HIV infections persists every year, with evidence that in some
      settings high-risk behaviour has increased, indicating failure in primary
      prevention. However, the vast majority of new infections still occur in
      developing countries. The two giants, India and China, are set to determine
      Asia's ultimate contribution to the pandemic, but currently it is Africa that
      remains in the eye of the storm, with rapidly increasing epidemics in many
      countries in the south and east of the continent impacting on all levels of
      society.

PMID- 10964277
TI  - Getting to know HIV.
AB  - Since the Human Immunodeficiency Virus was first isolated in 1983, we have come
      to know it in exquisite detail. Yet we still do not understand sufficiently how
      it causes disease. Neither do we know why chimpanzees and some African monkeys,
      which are the natural reservoir of the precursors of HIV-1 and HIV-2, can harbour
      similar levels of virus without becoming ill. Our knowledge of the replication
      cycle of HIV as a retrovirus has been pivotal in the development of antiviral
      drugs. Our knowledge of the cellular tropism and cell surface receptors exploited
      by the virus help to explain the pattern of immune deficiency, wasting and
      dementia that make up the clinical dimensions of AIDS. The extraordinary rate of
      genetic and phenotypic evolution of the virus - both within the infected
      individual and across the worldwide pandemic - partially explains why no vaccine
      constructs to date have been successful. HIV comprises just 9 genes but
      represents one of humanity's most formidable foes.

PMID- 10964278
TI  - Vaccines for the control of HIV/AIDS.
AB  - This review discusses the feasibility of an HIV vaccine and describes the
      history, efficacy and potential to succeed of old and new vaccine concepts.

PMID- 10964279
TI  - Some aspects of the natural history of HIV infection.
AB  - Studying factors influencing the length of the incubation period of HIV/AIDS is
      important to our understanding of the natural history of the disease and for the
      decision when to start with anti-retroviral therapy. In a multicentre study among
      HIV-positive homosexual men with a known date of seroconversion, we found that
      the median survival time after HIV infection was 12.1 years. Age is an important
      determinant of the survival: the older the shorter the incubation period and
      survival. Gender does not seem to play a role, but women appear to have higher
      CD4 counts than men at seroconversion, AIDS and death. HIV-positive drug users
      often die before they 'reach' AIDS often from HIV-related causes e.g. bacterial
      infections. In a multicentre study we found that such pre-AIDS mortality is now
      also found among homosexual men and haemophiliacs but at a much lower level. Most
      studies show that HIV subtype does not influence the incubation period. On the
      other hand genetic factors do play an important role.

PMID- 10964280
TI  - Therapeutic interventions in HIV infection - a critical view.
AB  - The introduction of highly effective combination regimens of antiretroviral drugs
      has led in recent years to substantial improvements in morbidity and mortality.
      As yet immune-based therapies have had little if any impact. However it is clear
      that eradication of HIV is not achievable with existing anti-HIV drugs and in
      spite of the major advances there remain many challenges in the clinical
      management of HIV-infected individuals. These benefits are unlikely to be
      extended to resource poor countries in the foreseeable future. The barriers are
      primarily but not only the costs. In resource-rich countries there are concerns
      about long term toxicities and many people have already exhausted all of the
      current therapeutic options. There is an urgent need for new drugs, ideally
      attacking new targets or with no cross resistance to existing drugs, and which
      are well tolerated and safe, easy to take and cheap. Many important questions
      still remain unanswered, in particular when to start antiretroviral therapy.

PMID- 10964281
TI  - Men's sexual health matters: promoting reproductive health in an international
      context.
AB  - Recent concern regarding the control of sexually transmitted infections (STIs)
      has resulted in an increased interest in the sexual health of men. This interest
      has primarily focused on strategies to 'encourage and enable men to take
      responsibility for their sexual and reproductive behaviour and their social and
      family roles' (United Nations 1994). Whilst men are deemed to have
      'responsibilities', women are said to have 'rights' with regard to making choices
      about reproductive health and accessing appropriate and effective services. Here
      it is argued that, whilst provision of services and interventions against STIs in
      men should never be at the expense of those for women, it is often clinically
      easier and more effective to diagnose and treat men with STIs compared to women
      in resource-poor settings. Indeed, this may prove to be an effective strategy in
      controlling the spread of STIs, and hence reducing the disproportionate burden of
      their complications suffered by women. The paper reviews key issues in relation
      to improved service delivery for sexual and reproductive health in men, notably:
      the heterogeneity of male populations; current knowledge regarding men's sexual
      behaviour; the role of sexuality; methods of studying sexual behaviour in
      resource poor countries; men's own concerns in relation to sexual and
      reproductive health; and where and how they access treatment. It is argued that
      the time has now come to determine and address men's sexual health needs if we
      are to expect them to participate fully as responsible partners in improving and
      protecting their own and others' sexual and reproductive health.

PMID- 10964282
TI  - Cardiovascular magnetic resonance imaging and spectroscopy in the new millennium.

PMID- 10964283
TI  - Second place-resident clinical science award 1999: laryngeal chemoreflex severity
      and end-apnea PaO(2) and PaCO(2).
AB  - OBJECTIVE: The laryngeal chemoreflex (LCR) is a model for investigating the
      sudden infant death syndrome. The severity of the LCR-induced response may vary.
      This study examines the conditions under which recovery from the LCR-induced
      apnea occurs. METHODS: Twenty-five piglets underwent normoxic laryngeal
      stimulation (Pao(2) > 70 mm Hg); 11 then underwent hypoxic stimulation (Pao(2) 50
      65 mm Hg). Cardiovascular and respiratory responses were recorded. RESULTS:
      Recovery Pao(2) was lower during profound responses (Pao(2) = 45.9 +/- 12.8 mm
      Hg) than during moderate (Pao(2) = 54.9 +/- 7.5 mm Hg) and mild (Pao(2) = 60.6 +/
      10.3 mm Hg) responses (analysis of variance [ANOVA], P = 0.05). Recovery PaCO(2)
      did not vary (ANOVA, P > 0.05). Blood pressure and O(2) saturation declined at
      faster rates with increasing severity of response (ANOVA, P < 0.05 for both).
      CONCLUSIONS: Resumption of respiration after LCR-induced apnea is associated with
      a consistent level of PaCO(2). The severity of the response is associated with
      recovery PaO(2) levels.

PMID- 10964284
TI  - Student Research Award 1999: comparative contrast of voice measurements.
AB  - Currently, a variety of objective and subjective measures are available to
      describe voice and voice function. Despite these various tools, there is no
      standard measure of voice function that incorporates both objective and
      subjective measures. The goal of this research was to study the relationship
      between objective, subjective, and patient-based measures of voice function.
      Objective voice function was measured with 4 laboratory-based parameters
      (subglottic pressure, airflow at the lips, maximum phonation time, and vocal
      efficiency), subjective function with the GRBAS (grade, rough, breathy, asthenic,
      strained) scale, and patient-based function according to an overall global rating
      of quality. The objective and subjective measures were significantly related to
      each other (P < 0.05); the objective and patient-based measures were also related
      (P = 0.019), but the subjective and patient-based measures were not related. We
      demonstrate a significant relationship between some but not all measures of voice
      function. We believe that subjective measures provide additional valuable
      information not obtained from objective measures alone.

PMID- 10964285
TI  - Migration of intradural epidermoid matrix: embryologic implications.
AB  - The migratory behavior of acquired cholesteatoma matrices (those arising from the
      tympanic membrane) has been described previously. This tissue is derived
      embryologically from the first branchial groove and represents the only migratory
      epithelium arising from the branchial groove system. If the matrix from a
      cerebellopontine angle (CPA) epidermoid tumor exhibits migratory behavior similar
      to that of acquired cholesteatomas, a first branchial groove site of origin for
      CPA epidermoids would be supported. Intradural CPA epidermoid cells were grown in
      alpha-minimum essential medium. The cultures were examined daily, and cell mass
      migration rates were measured. It was observed that intradural epidermoid tumor
      matrix harvested from the CPA exhibited migration in vitro. Its migratory
      properties were indistinguishable from those of acquired cholesteatomas, which
      are embryologically derived from the first branchial groove. These data support
      the theory that purely intradural epidermoids are derived from cells of the first
      branchial groove.

PMID- 10964286
TI  - Growth and development of the human cricoid cartilage: an immunohistochemical
      analysis of the maturation sequence of the chondrocytes and surrounding cartilage
      matrix.
AB  - OBJECTIVES: The goal was to determine maturational changes in the human cricoid
      cartilage. STUDY DESIGN: The study involved immunohistochemical staining of
      collagen II (a marker of proliferating chondrocytes), matrilin-1 (a marker of
      post-proliferative chondrocytes), and collagen X (a marker of hypertrophic
      chondrocytes). Specimens included uninjured human cricoid cartilages at 18 and 41
      weeks' gestation and 1, 4, and 13 years postpartum. RESULTS: This study
      demonstrated that type II collagen peaks in concentration at approximately 41
      weeks' gestation. Matrilin-1 is present in progressively lower concentration in
      the central core of the cricoid ring, but the peripheries of the ring contain the
      protein in relatively high concentration. Type X collagen is not expressed in the
      age groups tested. CONCLUSIONS: These biochemical markers lend further support to
      a chondrocyte proliferative phase that slows between 1 and 4 years of age.
      Chondrocytes then enter a phase histologically similar to the hypertrophic phase
      but are biochemically different than hypertrophic chondrocytes destined for
      endochondral ossification.

PMID- 10964287
TI  - Efficacy of uvulopalatopharyngoplasty in unselected patients with mild
      obstructive sleep apnea.
AB  - OBJECTIVES: Uvulopalatopharyngoplasty (UPPP) is widely used as a first-step
      procedure for the surgical management of obstructive sleep apnea (OSA) syndrome
      but best manages obstruction occurring at the level of the oropharynx alone and
      not the hypopharynx. Previous publications have noted mediocre results with use
      of this procedure in unselected patients with OSA, but less clear is the
      effectiveness of this procedure in the unselected patient with mild OSA
      (respiratory event index [REI] 5-25). Using objective and subjective criteria, we
      retrospectively analyzed the results of UPPP in patients with mild OSA. METHODS:
      We examined 37 patients with mild OSA (REI 13.5 +/- 5.1, range 5.6-23.1) who had
      been operated on during 1996 with UPPP with or without tonsillectomy and/or
      septoplasty. Follow-up polysomnography was obtained in 25 (68%) an average of
      40.5 weeks after surgery and compared with findings before surgery. Subjective
      assessment of sleepiness was performed with the Sleep-Wake Activity Inventory.
      RESULTS: Ten patients (40%) had a postoperative reduction in the REI of more than
      50%, comparable with the improvements reported in those with more severe apnea.
      Those who did not have a reduction in REI after surgery actually saw an increase
      in average REI from 16.6 +/- 5 to 26.7 +/- 18.4. Similarly, subjective assessment
      of sleepiness with the Sleep-Wake Activity Inventory showed no statistically
      significant improvement after surgery. CONCLUSION: Overall, these results
      indicate that UPPP alone in the unselected patient provides little benefit in the
      management of mild OSA, similar to findings for more severe OSA. Surgeons must
      use great care in discerning the level of obstruction in the patient with mild
      OSA to tailor the appropriate retropalatal and/or retrolingual procedures and
      thereby achieve excellent surgical outcomes.

PMID- 10964288
TI  - Efficacy of immunotherapy based on skin end-point titration.
AB  - OBJECTIVE: The purpose of this study is to examine the efficacy of skin end-point
      titration (SET) as a method of assessing skin responsiveness, selecting antigens,
      and initiating treatment for successful inhalant immunotherapy. STUDY DESIGN:
      This study is a prospective, randomized, controlled, double-blind investigation.
      Eighteen patients were randomly assigned to 1 of 2 groups: an experimental group
      treated for all positive antigens, and a control group treated for all positive
      antigens, with the exception of the study antigens. Quality of life was assessed
      with 3 dependent measures, and response to nasal challenge and nasal endoscopic
      evaluations were conducted. Ten patients completed the 6-month study. RESULTS:
      There were significant improvements in the emotional component of sinus-related
      disability, in response to nasal challenge, and in the endoscopic appearance of
      the mucosa, regardless of patient group. There was a trend toward improved
      quality of life among experimental subjects. CONCLUSIONS: SET-based immunotherapy
      reduces self-rated disability over time. In addition, SET-based immunotherapy
      allows decrease in nasal reactivity and normalizes the endoscopic appearance of
      the nose.

PMID- 10964289
TI  - Image-guided functional endoscopic sinus surgery.
AB  - INTRODUCTION: Computer-aided surgery (CAS) technology in functional endoscopic
      sinus surgery (FESS) has engendered considerable discussion. OBJECTIVE: The goals
      of this study were to describe CAS preoperative planning (software-based CT image
      analysis) and to develop intraoperative CAS strategies for endoscopic sinus
      surgery. STUDY DESIGN: Between October 1, 1997, and December 31, 1998, the
      StealthStation (Sofamor Danek, Memphis, TN) was used in 61 FESS cases, and a
      retrospective review of the findings was performed. The indication for surgery in
      all instances was chronic rhinosinusitis refractory to medical management. The
      StealthStation was used to review all CT scans before surgery. Anatomic fiducial
      registration supplemented by contour mapping was used. RESULTS: Localization
      accuracy was estimated to be within 2 mm or better. The StealthStation was used
      for both CT image review and intraoperative localization. CAS was useful in the
      frontal recess, sphenoethmoid region, posterior ethmoid system, and skull base
      area. CAS was deemed helpful in situations where the surgical anatomy was altered
      by previous surgery and extensive inflammatory disease (polyposis, fungal
      sinusitis, and pansinusitis). CONCLUSION: The paradigm of image-guided FESS
      surgery, which integrates CAS into FESS, will serve to increase surgical
      effectiveness and decrease surgical morbidity.

PMID- 10964290
TI  - Endoscopic repair of cerebrospinal fluid leaks to the sinonasal tract: predictors
      of success.
AB  - INTRODUCTION: Cerebrospinal fluid (CSF) leaks may arise as a complication of
      endoscopic sinus surgery, trauma, or hydrocephalus, or they may occur
      spontaneously without any identifiable cause. Despite general agreement that CSF
      leaks should not be left untreated, their initial management, the surgical
      indications, and the technique of repair are controversial. OBJECTIVE: We
      undertook this study to ascertain whether a particular surgical technique or
      material was more successful for repair. Additionally, we tried to identify which
      specific characteristics of the patient, the CSF fistula, or the adjunctive
      treatment influenced the result of the repair. STUDY DESIGN: We completed a
      retrospective review of all patients undergoing endoscopic repair of a CSF leak
      at our academic hospitals. RESULTS: Forty-eight patients with 53 CSF fistulas
      were included in the study. Fifty sites were successfully repaired endoscopically
      on the first attempt. Three persistent leaks were repaired successfully on the
      second attempt. Location and size of the leak, cause, technique, and choice of
      material used for the repair did not significantly affect surgical outcome.
      However, the presence of hydrocephalus had a statistically significant negative
      influence on surgical outcome. All patients with increased intraventricular
      pressure required a ventricular shunt in addition to a second endoscopic repair.
      CONCLUSION: If the surgical technique is sound, endoscopic repair of CSF leaks is
      highly successful, independent of the choice of the material and technique used
      in the repair.

PMID- 10964291
TI  - Surgical management of carotid body tumors.
AB  - OBJECTIVE: The goal was to review our experience in the management of carotid
      body tumors at a tertiary referral center. METHODS: A retrospective review was
      performed of patients at University of California-Los Angeles Medical Center in
      whom carotid body tumor was diagnosed between 1973 and 1998. RESULTS: Twenty-nine
      patients with 36 carotid body tumors were identified. Thirty-five operations were
      performed. Seventeen patients underwent preoperative embolization. The blood loss
      for these patients was less than for those without embolization. Five patients
      had preoperative cranial nerve deficits. Neurologic deficits were noted in 41% of
      patients immediately after surgery. In 24% of patients, the deficits were
      permanent. CONCLUSION: Surgical resection is the treatment of choice for carotid
      body tumors. Embolization immediately before surgery decreases blood loss and
      facilitates tumor removal. In our series, the risk of new postsurgical cranial
      nerve deficits was small. Observation of these tumors is not recommended because
      progressive growth is associated with increased risk of neurologic deficits.

PMID- 10964292
TI  - Squamous cell carcinoma of the anterior nasal cavity: a dual institution review.
AB  - Thirty-two patients with squamous cell carcinoma of the anterior nasal cavity
      were identified at two university hospitals. A retrospective review was conducted
      to identify clinical presentation, initial therapy, recurrence rates, and factors
      affecting survival. Treatment included surgery (n = 15), radiation therapy (n =
      9), or combination therapy (n = 8). The primary lesions involved either the
      septum, vestibule, columella, anterior floor, or a combination of these subsites.
      The primary tumor involved a single nasal subsite in 22 patients and multiple
      nasal subsites in 10 patients. All patients had de novo squamous lesions, and all
      tumors were staged N0 at initial diagnosis. Six patients received prophylactic
      neck irradiation, and none underwent elective neck dissection. Overall, 18 (56%)
      patients had recurrent disease after primary therapy (5 local and 13 regional).
      The 5-year disease-free survival was 42%, and the 5-year overall survival was
      50%. None of the patients receiving prophylactic neck irradiation had a regional
      recurrence. Involvement of 2 or more nasal subsites significantly decreased
      survival (P < 0.05). Squamous cell carcinoma of the anterior nasal cavity is an
      aggressive disease, and combined therapy initially with strong consideration for
      prophylactic radiation to the facial and cervical lymphatics is advocated.

PMID- 10964293
TI  - Risk factors associated with hypothyroidism after laryngectomy.
AB  - Hypothyroidism is a well-documented complication after treatment of head and neck
      cancer and is particularly significant among patients undergoing laryngectomy.
      The objective of this study was the identification of factors associated with the
      development of hypothyroidism in this population. Records of 136 patients treated
      with laryngectomy were retrospectively reviewed in an attempt to define a risk
      factor profile for patients in whom hypothyroidism is most likely to develop
      after laryngectomy. The Cox proportional hazards model was used to identify
      factors significantly related to an increased risk for development of
      hypothyroidism. The actuarial method was used to estimate the period of greatest
      risk for the development of hypothyroidism. Increased risks were found for
      patients who were female (P = 0.0049), received preoperative radiation therapy (P
      = 0.0022), had invasion of the thyroid gland by tumor (P = 0.0003), had presence
      of cervical metastases (P = 0.0022), and had postoperative fistula (P = 0.0095).
      From the actuarial method, we estimated that the period of time when patients
      were at greatest risk for development of hypothyroidism was between 0 and 14
      months after surgical intervention. Wound complications were twice as frequent in
      hypothyroid patients. Perioperative awareness of risk factors associated with the
      development of hypothyroidism in patients undergoing laryngectomy allows for
      early recognition and management of hypothyroidism and may reduce the number of
      complications related to wound healing and fistula.

PMID- 10964294
TI  - Endoscope-assisted microvascular decompression of the trigeminal nerve.
AB  - Twenty-one patients with classic symptoms of trigeminal neuralgia underwent
      microvascular decompression of the trigeminal nerve through a retrosigmoid
      approach to the cerebellopontine angle. Endoscopy was used as an adjunctive
      imaging modality to microscopy. Specifically, endoscopes were used to confirm
      nerve-vessel conflicts identified by the microscope and to reveal others that
      escaped microscopic survey. Endoscopes were also used to assess the adequacy of
      the decompression performed microscopically. A total of 51 nerve-vessel conflicts
      were identified and treated, 14 of which were discovered only after endoscopy.
      Additionally, in 5 patients endoscopic examination of the surgical intervention
      demonstrated that further maneuvers were required to completely decompress the
      nerve. These results highlight the value of endoscopy in the diagnosis and
      therapy of cranial nerve pathology in the posterior fossa.

PMID- 10964295
TI  - Osteoradionecrosis of the maxillary-orbital complex after neutron beam
      radiotherapy.
AB  - OBJECTIVE: Neutron beam radiotherapy (NRT) has been advocated for treatment of
      malignant salivary gland tumors and adenoid cystic carcinoma of the paranasal
      sinuses. The purpose of this study is to determine whether primary or adjuvant
      NRT results in a significantly increased rate of osteora-dionecrosis (ORN) of the
      maxillary-orbital complex (MOC). STUDY DESIGN AND SETTING: All patients who
      received primary or adjuvant NRT involving the MOC and/or maxillofacial
      prosthetic rehabilitation at Wayne State University from 1992 to 1997 were
      evaluated (n = 9). RESULTS: ORN did not develop in any of the 5 patients who
      received primary NRT. All 4 patients who received adjuvant NRT after surgical
      resection had ORN involving the MOC within the irradiated fields. CONCLUSION: The
      reported trend of ORN after definitive surgery and NRT shows a markedly increased
      complication rate. SIGNIFICANCE: The use of adjuvant NRT after definitive
      surgical resection involving the MOC should be considered with great caution.

PMID- 10964297
TI  - Chest radiographs after dilatational percutaneous tracheotomy: are they
      necessary?
AB  - BACKGROUND: The efficacy of routinely obtaining chest radiographs after standard
      open tracheotomy has been questioned. Recent literature would suggest that after
      a routine, uncomplicated tracheotomy, chest radiography is a low-yield procedure
      that incurs unnecessary expense. Percutaneous dilatational tracheotomy (PDT) is
      rapidly replacing open tracheotomy as the intensive care unit procedure of choice
      for airway management. Complication rates are equivalent between the two
      procedures. OBJECTIVE: We examined the value and cost-effectiveness of routine
      postoperative chest radiographs in patients undergoing PDT. STUDY DESIGN AND
      SETTING: The study was a prospective analysis of 54 consecutive PDTs performed at
      a tertiary care academic institution. RESULTS: Eighteen (33%) patients had chest
      radiographs obtained within 1 hour of PDT (6 at the request of the otolaryngology
      service); 35 (66%) underwent radiography more than 2 hours later at the request
      of the intensive care unit for reasons other than PDT. There were no incidents of
      pneumothorax, pneumomediastinum, or tracheotomy tube malposition in any patient.
      Patients undergoing chest radiography within 1 hour of the PDT also had chest
      radiographs within 12 hours at the request of ICU staff for their underlying
      disease. CONCLUSIONS: Routine chest radiography after PDT is of low yield.
      Because most of these patients require chest radiographs for their underlying
      disease within 12 hours, a cost savings of approximately $13,500 would be
      realized in this patient population. SIGNIFICANCE: Routine chest radiography
      after PDT is unwarranted in most cases.

PMID- 10964296
TI  - Evaluation of posttonsillectomy hemorrhage and risk factors.
AB  - BACKGROUND: A 13-year retrospective study was undertaken to determine the
      incidence of posttonsillectomy hemorrhage, to evaluate potential risk factors,
      and to assess the efficacy and safety of ambulatory tonsillectomy. METHODS: From
      January 1985 to December 1997, 4662 patients underwent tonsillectomy at our
      institution. Ninety patients with posttonsillectomy bleeding were identified. For
      each patient with posttonsillectomy bleeding, 2 nonbleeding control subjects were
      selected and matched by age and sex to evaluate potential risk factors. RESULTS:
      Age was the only factor found to be statistically significant among the bleeding
      patients and the control group. The highest incidence (3.61%) of
      posttonsillectomy hemorrhage occurred in patients 21 to 30 years of age. In our
      experience, secondary hemorrhage was more common than primary hemorrhage,
      presenting most frequently on postoperative days 5 to 7. CONCLUSIONS: The
      incidence of posttonsillectomy bleeding in this review was 1.93%, and about half
      (47%) of the patients with posttonsillectomy hemorrhage returned to the operating
      room for hemorrhage control. The highest incidence (3.61%) of posttonsillectomy
      hemorrhage occurred in patients 21 to 30 years of age. Patients with
      posttonsillectomy hemorrhage, regardless of management, had a 12% incidence of
      subsequent hemorrhage. We found no difference in the incidence of
      posttonsillectomy bleeding between outpatient and inpatient procedures.

PMID- 10964298
TI  - Predictors of airway intervention in angioedema of the head and neck.
AB  - OBJECTIVE: Records of patients presenting with angioedema of the head and neck
      were analyzed to determine clinical factors that predict the need for airway
      intervention. METHODS: A review of patients with angioedema of the head and neck
      over a 10-year period was conducted. Data were collected regarding demographics,
      cause of edema, and sites of involvement. A logistic regression model was used to
      ascertain whether any clinical variables were significant in predicting the need
      for airway intervention. RESULTS: Review of 138 charts with an admitting
      diagnosis of angioedema yielded 66 cases of angioedema of the head and neck in 48
      patients. Twenty-three (34.8%) patients required airway intervention. Logistic
      regression identified increasing age and angioedema involving the oral
      cavity/oropharynx as predictors of airway intervention; involvement of other
      sites, cause, and sex were not predictive. CONCLUSION: Location of edema and
      patient age predict which patients with angioedema of the head and neck are
      likely to require airway intervention.

PMID- 10964299
TI  - In vitro resistance to bacterial biofilm formation on coated fluoroplastic
      tympanostomy tubes.
AB  - Bacterial biofilm formation has been implicated in persistent posttympanostomy
      otorrhea and irreversible tube contamination. The use of a tympanostomy tube with
      a resistance to biofilm formation by the most common organisms associated with
      persistent infection may decrease the incidence of chronic otorrhea and the need
      for tube removal. In this investigation, scanning electron microscopy was used to
      compare a phosphorylcholine-coated fluoroplastic tympanostomy tube to plain
      fluoroplastic and silver oxide-impregnated fluoroplastic for resistance to
      biofilm formation after in vitro incubation with Staphylococcus aureus or
      Pseudomonas aeruginosa. Only a biofilm from Pseudomonas formed on the untreated
      fluoroplastic tubes, whereas the silver oxide-impregnated tubes developed
      biofilms from both S aureus and P aeruginosa. In contrast, the coated
      fluoroplastic tube showed resistance to both staphylococcal and pseudomonal
      biofilm adhesion. This is the first study to demonstrate the effect of a surface
      treatment of fluoroplastic as a method to inhibit biofilm formation by both S
      aureus and P aeruginosa. This reinforces our previous studies showing that
      surface-adherence properties such as charge or slickness or both may be more
      beneficial than antibacterial treatments in preventing film adhesion.

PMID- 10964300
TI  - Temporal bone necrosis: diagnosis, classification, and management.
AB  - OBJECTIVE: The goal of this study was to analyze temporal bone necrosis and
      classify its diagnosis and treatment according to extent of necrosis and cause.
      METHODS AND MATERIAL: Twenty-six cases of temporal bone necrosis were
      retrospectively reviewed between 1988 and 1997 at the University of British
      Columbia. RESULTS: Patients were classified on the basis of disease extent
      restricted to the tympanic bone or extension beyond the tympanic bone, as well as
      on the basis of the cause of disease; treatment based on classification. Patients
      with localized disease of the tympanic bone had minimal symptoms. Those with
      radiation-induced localized necrosis were less likely to respond to conservative
      medical management. Patients with diffuse disease were more likely to require
      surgical intervention. CONCLUSIONS: Temporal bone necrosis comprises a spectrum
      of disease from idiopathic tympanic bone necrosis, which rarely requires surgery,
      to the more severe forms of radiation-induced diffuse temporal bone necrosis that
      may cause life-threatening complications requiring surgical intervention.

PMID- 10964301
TI  - Tympanic membrane and middle ear pathologic correlates in mucoid otitis media.
AB  - OBJECTIVE: The goal of this study was to correlate tympanic membrane (TM) and
      middle ear (ME) pathologies in mucoid otitis media (MOM). METHODS AND MATERIAL:
      Forty ears with MOM and 56 control ears were retrospectively evaluated for TM and
      ME pathologies. Comparisons of TM thicknesses in MOM versus control ears were
      correlated with the Student t test; chi(2) analysis was used to correlate
      pathologic findings of the TM and ME. RESULTS: Thicknesses in all quadrants
      except the umbo were increased in MOM because of infiltration of inflammatory
      cells and fibrosis. The most common ME pathologies were granulation tissue and
      fibrosis. Significant correlations included (1) TM retraction and ME granulation
      tissue and fibrosis and (2) pars flaccida, posterosuperior, and anteroinferior
      thickness and ME granulation tissue and fibrosis. CONCLUSION: TM changes are
      likely to occur in patients with otitis media with effusion (MOM), and their
      presence is a strong indication of underlying ME pathology.

PMID- 10964302
TI  - Is tracheotomy decannulation possible in oxygen-dependent children?
AB  - OBJECTIVE: The goal was to determine whether decannulation can be safely achieved
      in children with persistent oxygen requirements. DESIGN: The study was a
      prospective evaluation of 12 oxygen-dependent children at a tertiary care
      academic children's medical center. METHODS: Twelve tracheotomy-dependent
      children with persistent oxygen requirements were evaluated for decannulation.
      Patients requiring more than 35% FiO(2) were not considered. Direct laryngoscopy
      and bronchoscopy were performed in all patients. Two required single-stage
      laryngotracheoplasty to correct subglottic stenosis, 1 required tracheal
      resection, and 7 required removal of suprastomal granulation tissue. Oxygen was
      administered after decannulation through a nasal cannula. RESULTS: Decannulation
      was successful in 92% (11 of 12) of patients. At final follow-up, oxygen
      requirements decreased in 58% of patients after decannulation. CONCLUSIONS:
      Decannulation can be successful in children who remain oxygen dependent;
      conversion to a more physiologic airway may be an adjunct to reducing or
      eliminating their oxygen demand.

PMID- 10964303
TI  - Fibromatosis of the head and neck: a challenging lesion.
AB  - Fibromatosis is a histologically benign fibrous neoplasm that arises from the
      musculoaponeurotic tissues of the body. It can have significant morbidity when it
      occurs in the head and neck region because of the proximity of vital structures.
      This review article considers the etiology, demographics, pathology, natural
      history, and various treatment modalities for this lesion. Therapeutic guidelines
      are provided.

PMID- 10964304
TI  - Nager acrofacial dysostosis with autosomal dominant inheritance: implications for
      the otolaryngologist.

PMID- 10964305
TI  - Isolated cryptococcal sphenoid sinusitis with septicemia, meningitis, and
      subsequent skull base osteomyelitis in an immunocompetent patient.

PMID- 10964306
TI  - Hypopharyngeal desmoid tumor.

PMID- 10964307
TI  - Intracochlear vestibular schwannoma: a potential source for recurrence after
      translabyrinthine resection.

PMID- 10964308
TI  - Recurrence of attic cholesteatoma: different methods of estimating recurrence
      rates.
AB  - One problem in cholesteatoma surgery is recurrence of cholesteatoma, which is
      reported to vary from 5% to 71%. This great variability can be explained by
      issues such as the type of cholesteatoma, surgical technique, follow-up rate,
      length of the postoperative observation period, and statistical method applied.
      The aim of this study was to illustrate the impact of applying different
      statistical methods to the same material. Thirty-three children underwent single
      stage surgery for attic cholesteatoma during a 15-year period. Thirty patients
      (94%) attended a re-evaluation. During the observation period of 15 years,
      recurrence of cholesteatoma occurred in 10 ears. The cumulative total recurrence
      rate varied from 30% to 67%, depending on the statistical method applied. In
      conclusion, the choice of statistical method should depend on the number of
      patients, follow-up rates, length of the postoperative observation period and
      presence of censored data.

PMID- 10964309
TI  - Modified supracricoid partial laryngectomy with cricohyoidopexy: series report
      and analysis of results.
AB  - Aiming to improve voice quality and to facilitate swallowing rehabilitation, we
      modified the supracricoid partial laryngectomy with cricohyoidopexy by preserving
      the posterior segment of the true vocal cord on the less involved side of the
      larynx. Between 1983 and 1994, 13 patients with supraglottic cancer were treated
      with this modified procedure. The possibility of incomplete tumor excision was
      eliminated by careful patient selection and intraoperative reconfirmation of
      tumor extent with frozen sections. Our results have been promising, with a 76.9%
      3-year survival rate and a 69.2% laryngeal preservation rate. There were 7
      recurrences, 3 local (2 at the superior border of the cricoid and 1 at the
      cricoarytenoid region) and 4 nodal, in 5 patients. Distant metastases developed
      in another patient. Three patients, 2 with local and nodal recurrence and 1 with
      distant metastases, died of disease. Functional outcomes were also good, with all
      patients achieving normal swallowing by the end of the first year, although 5
      patients required temporary gastrostomy for transient swallowing impairment.
      Early decannulation and satisfactory voice quality were achieved in all cases. We
      believe that with proper patient selection this modified procedure is effective
      both for tumor control and for preserving a more functional larynx.

PMID- 10964310
TI  - 2[F]-fluoro-2-deoxy-D-glucose positron emission tomography is a sensitive tool
      for the detection of occult primary cancer (carcinoma of unknown primary
      syndrome) with head and neck lymph node manifestation.
AB  - BACKGROUND: The neck lymph nodes are a common site of metastases from carcinoma
      of unknown primary (CUP syndrome). 2[(18) F]-fluoro-2-deoxy-D-glucose positron
      emission tomography (18-FDG-PET) has been shown to be a sensitive tool for
      detecting primary malignant lesions as well as metastatic spread. We have
      prospectively investigated the sensitivity of 18-FDG-PET in detecting occult
      primary carcinomas with manifestation in the head and neck lymph nodes. METHODS:
      From May 1994 to July 1998, in 723 patients a cancer of the head and neck was
      diagnosed at the University of Cologne ENT outpatient clinic. The routinely
      performed staging procedures were chest radiography; full blood count; cervical
      and liver ultrasound; endoscopy of the nasopharynx, oropharynx, hypopharynx,
      larynx, and esophagus; and laboratory analyses. After the staging workup, in 27
      of 723 patients (3.7%) CUP syndrome had to be presumed because the primary cancer
      could not be detected. In these patients 18-FDG-PET was performed, and images
      were reconstructed with a transmission-emission fusion technique. RESULTS: In 7
      of 27 patients (26%) 18-FDG-PET revealed an unknown primary: in 2 a bronchial
      carcinoma, in 2 a nasopharyngeal carcinoma, in 1 a squamous cell carcinoma of the
      parotid gland, in 1 a squamous cell carcinoma of the hypopharynx, and in 1 a
      carcinoma of the tonsil. In 4 of 7 patients the occult primary tumor was removed
      surgically. In 8 of 27 patients therapeutic strategy was changed as a result of
      the 18-FDG-PET findings. CONCLUSION: 18-FDG-PET should be performed in all
      patients with CUP syndrome after conventional diagnostic workup fails to identify
      the primary.

PMID- 10964311
TI  - Pain in the neck after neck dissection.
AB  - BACKGROUND: Reports of disability after neck dissection have been directed toward
      shoulder dysfunction and pain. We could find no report addressing the issue of
      pain localized to the actual operative site. We have conducted a combined
      prospective and retrospective study of pain in patients undergoing neck
      dissection. METHODS: Eighty-eight disease-free patients were evaluated in 3
      groups for neck pain. One group was followed up prospectively for 1 to 8 months
      after surgery, and 2 retrospective groups were followed up for more than 2 years
      or for 6 months to 2 years. Pain was assessed by a body map and visual analog
      scale. RESULTS: None of 31 patients followed up for more than 2 years reported
      neck pain. Four of 27 patients followed up for 6 to 24 months had pain, with a
      mean visual analog scale score of 3.7. Seventy percent of the prospective group
      of 30 patients had pain during the first postoperative week, and only 1 patient
      had pain persisting for more than 2 months. Shoulder pain and disability after
      radical neck dissection were encountered in all groups, comparable with the
      incidence reported in the literature. No postoperative neuromas were found.
      CONCLUSIONS: Chronic pain localized to the operative site is an uncommon
      occurrence even after radical neck dissection. Chronic pain in the shoulder
      region may follow radical neck dissection, whereas modified neck dissection is
      usually a painless procedure.

PMID- 10964312
TI  - Intranasal anatomy of the nasolacrimal sac in endoscopic dacryocystorhinostomy.
AB  - Intranasal surface anatomy is fundamental to the technique of endoscopic
      dacryocystorhinostomy. In the current literature the lacrimal sac is described as
      being situated anterior to the anterior end of the middle turbinate with between
      0% and 20% of the sac above the insertion of the middle turbinate on the lateral
      nasal wall (the axilla of the middle turbinate). The aim of this study was to use
      CT dacryocystograms (DCGs) and CT scans to establish the relationship of the
      lacrimal sac to the lateral nasal wall. Forty-seven individual lacrimal sacs were
      measured in relation to the common canaliculus, and 76 were measured in relation
      to the insertion of the middle turbinate. Measurements taken from the long axis
      of the sac showed the mean height of the sac above the middle turbinate insertion
      was 8.8 mm (SD = 0.2, 95% CI = 1.3) and below it was 4.1 mm (SD = 2.3, 95% CI =
      1.1). The average measurement of the sac above the com-mon canaliculus on CT DCGs
      was 5.3 mm (SD = 1.7, 95% CI = 0.56), whereas the average measurement below the
      common canaliculus was 7.7 mm (SD = 2, 95% CI = 1.3) (n = 47 CT DCGs). The
      findings in this study show that a major portion of the sac is locat-ed above the
      insertion of the anterior end of the middle turbinate and, in addition, that a
      significant part of the sac lies above the entry point of the common canaliculus.
      Knowledge of these findings can ensure that the sac is adequately exposed during
      dacryocystorhinostomy by removal of sufficient bone and mucosa above the anterior
      insertion of the middle turbinate.

PMID- 10964313
TI  - Endoscopic management of foreign bodies in the tracheobronchial tree: predictive
      factors for complications.
AB  - We reviewed the records of 504 patients admitted to the American University of
      Beirut Medical Center during a 10-year period for treatment of aspiration of a
      foreign body into the tracheobronchial tree. All underwent rigid fiberoptic
      bronchoscopy for removal of the foreign body. Complications occurred in 42
      patients (8%) and were classified as intraoperative (7 patients), postoperative
      (25 patients), and failure to retrieve the foreign body by bronchoscopy (9
      patients). These complications included respiratory distress necessitating
      tracheotomy and/or assisted ventilation, bronchial pneumonia, pneumothorax,
      bradycardia, and cardiac arrest. Variables that were examined were the age and
      sex of the patient, history of multiple previous bronchoscopies, delay in
      diagnosis and/or treatment, duration of the procedure, type and location of the
      foreign body, and use of corticosteroids during surgery. The most important
      variables that were of value in predicting the occurrence of complications were
      the history of previous bronchoscopy, the duration of the procedure, and the type
      of foreign body. Age, sex, delay in diagnosis and treatment, and intraoperative
      use of corticosteroids, while important, had no predictive value. Detailed
      results with guidelines for prevention and management are presented.

PMID- 10964314
TI  - Reconstruction of lower lip defects after tumor excision: an aesthetic and
      functional evaluation.
AB  - We are presenting a new questionnaire to evaluate the functional and aesthetic
      aspects after reconstruction of defects of the lower lip resulting from tumor
      excision. The questionnaire is based on objective parameters with numerical
      values. The application of the questionnaire is carried out based on 2 different
      surgical techniques, which have been used in the Department of Oral and
      Maxillofacial Surgery of La Princesa University Hospital in Madrid. These
      techniques are used in the reconstruction of surgical defects and concern the
      location and percentage of the lip resection. These techniques are the rotation
      advancement flap by Yu and the rotation-advancement in island flap by Colmenero
      et al. The defects are located laterally and they include 40% to 60% of the
      length of the lip, avoiding the commissure. There is also one case with a defect
      that is almost 100% of the length of the lip. According to the questionnaire, we
      conclude that in unilateral defects that exceed 50% (up to 70%), Yu's technique
      provides better results from an aesthetic and functional point of view than
      Colmenero's technique. In subtotal defects, bilateral Yu flaps provide optimum
      function, with good position of the scars. This is a technique to be considered
      when confronted with extensive defects of the lip that do not include the
      commissures.

PMID- 10964315
TI  - Magnetic resonance imaging versus clinical palpation in evaluating cervical
      metastasis from head and neck cancer.
AB  - We prospectively compared the value of MRI and clinical palpation for detecting
      cervical metastases in patients with primary cancer of the head and neck. Sixty
      patients with squamous cell carcinoma of the upper aerodigestive tract were
      evaluated with MRI and clinical palpation before undergoing a total of 81 neck
      dissections. The results of preoperative clinical palpation and MRI were compared
      with the histopathologic outcome. The sensitivity and specificity were 75.6% and
      97.5%, respectively, for clinical palpation and 73.2% and 95%, respectively, for
      MRI. The rate of occult cervical metastasis was 24% with clinical palpation and
      26.8% with MRI. The use of MRI did not improve the rate of early detection of
      occult metastasis, nor did it improve the detection of extracapsular spread. Our
      findings show that we could not depend on palpation or MRI alone to determine the
      need for elective neck dissection. However, MRI can be used to improve the
      preoperative grading of cervical lymph nodes. In selected cases, this may direct
      surgeons to convert the treatment plan to choose a more conservative neck
      dissection or, after sentinel node sampling and frozen-section control, to
      convert the treatment to a more radical dissection.

PMID- 10964316
TI  - Factors affecting wound infection rates in head and neck surgery.
AB  - PURPOSE: This study was planned with 2 goals in mind: to evaluate the efficacy of
      prolonged and 1-day antibiotic regimens for prophylaxis and to evaluate the
      effect of various factors such as neck dissection, localization and stage of
      tumor, type of laryngectomy, and history of prior radiotherapy, tracheotomy, and
      diabetes mellitus on postoperative wound infection rates. METHODS AND MATERIAL:
      In this study, 408 head and neck procedures (201 clean and 207 clean
      contaminated) performed at our institution were retrospectively reviewed.
      RESULTS: Prolonged and 1-day antibiotic regimens for both clean and clean
      contaminated procedures were similar in efficacy (7% vs 3% for clean procedures
      [P = 0.165] and 30% vs 28% for clean-contaminated procedures [P = 0.777]). The
      wound infection rate was higher (13%) after clean radical neck dissections versus
      other clean procedures (1%) (P = 0.001). For clean-contaminated procedures,
      factors affecting postoperative wound infection rates were performance of
      bilateral neck dissections (P = 0.014), disease stage (P = 0.002), type of
      laryngectomy (P = 0.002), and history of prior tracheotomy (P = 0.006).

PMID- 10964317
TI  - Intracapsular enucleation of vagus nerve-originated tumors for preservation of
      neural function.

PMID- 10964318
TI  - Polymorphous low-grade adenocarcinoma of the submandibular gland.

PMID- 10964319
TI  - Cryptotia.

PMID- 10964320
TI  - Major aphthous ulcer in an HIV-positive child.

PMID- 10964321
TI  - The workforce in otolaryngology-head and neck surgery: moving into the next
      millennium.
AB  - OBJECTIVE: The goal was to examine the current scope of otolaryngologists'
      practices, their geographic distribution, and the roles otolaryngologists and
      other specialists play in caring for patients with otolaryngic and related
      conditions of the head and neck. STUDY DESIGN: A large national survey and
      administrative claims databases were examined to develop practice profiles and
      compile a physician supply for otolaryngology. A focus group of otolaryngologists
      provided information to model future scenarios. RESULTS: The current and
      predicted workforce supply and demographics are at a satisfactory level and are
      decreasing as a proportion of the increasing population. Empiric data analysis
      supports the diverse nature of an otolaryngologist's practice and the unique role
      for otolaryngologists that is not shared by many other providers. Together with
      the focus group results, the study points to areas for which more background and
      training are warranted. CONCLUSIONS: This study represents a first step in a
      process to form coherent workforce recommendations for the field of
      otolaryngology.

PMID- 10964322
TI  - Preoperative induction chemotherapy followed by concurrent chemoradiotherapy in
      advanced carcinoma of the oral cavity and oropharynx.
AB  - BACKGROUND: Combined modality therapy plays a central role in the management of
      advanced head and neck tumors. The objective of our Phase II study was to
      determine the feasibility, toxicity, and clinical and pathologic response of
      preoperative induction chemotherapy, followed by concurrent chemoradiotherapy in
      patients with Stage III or IV squamous cell carcinoma according to the American
      Joint Committee on Cancer Staging of the oral cavity and oropharynx with no
      distant metastases. METHODS: After staging, 62 patients with locally advanced
      carcinoma of the oral cavity and oropharynx were treated preoperatively with
      chemotherapy (1 cycle of cisplatin and 5-fluorouracil [P-5FU]) followed by
      concurrent chemoradiotherapy (3 cycles of P-5FU combined with radiotherapy, 60
      grays [Gy] given in 33 fractions of 1.8 Gy). After evaluation, patients underwent
      surgery either as a diagnostic (biopsy) or therapeutic procedure (resection of
      the primary tumor and/or the neck). Surgery was performed with the intent to
      spare organ function. RESULTS: Grade 3-4 mucositis was observed in 37 patients
      (59%). Overall clinical response was obtained in 87%, and the complete clinical
      response rate was 50%. Surgery was performed in 53 patients, 50 at the primary
      tumor site (11 biopsies, 14 marginal excisions, and 25 wide excision) and 46
      patients had neck dissection. Pathologic complete remission was observed in 29
      patients (46%). After a median follow-up of 39 months, locoregional control rate
      was 76%, estimated 3-year disease free survival rate was 73% (+/- 4%), and
      estimated 3-year overall survival rate was 76% (+/- 4%). CONCLUSIONS: This
      intensive multimodality treatment is feasible, and toxicity is significant but
      tolerable. The treatment results appear promising and durable. Organ-preserving
      surgery can be performed in many patients.

PMID- 10964323
TI  - Combined chemotherapy and radiotherapy followed by surgery in the treatment of
      patients with squamous cell carcinoma of the esophagus.
AB  - BACKGROUND: Surgery remains the treatment of choice for patients with esophageal
      squamous cell carcinoma (SCC), but survival rates have not improved over the past
      decades. The objective of this study was to evaluate the effect of multimodal
      therapy on resectability, on the overall and on disease free survival (DFS)
      rates, and on the laryngeal resection rate. METHODS: Fifty-five patients (49 men
      and 6 women) with a mean age of 58 +/- 8 years underwent combined modality
      treatment for esophageal SCC. The tumor location was in the upper one-third of
      the esophagus in 19 patients, the middle one-third in 22 patients, the lower one
      third in 9 patients, and the upper and lower one-thirds in 5 patients. The intent
      of combined therapy was curative in 87.3% of patients and palliative in 12.7% of
      patients. Neoadjuvant treatment consisted of two courses of 5-fluorouracil and
      cisplatin on Days 1-5 and Days 21-25. Radiotherapy was commenced on Day 21 and
      consisted of 36 grays delivered in 12 fractions over 17 days. Surgery was
      performed on Day 60. RESULTS: Full neoadjuvant treatment was possible in 67.3% of
      patients and was uneventful in 56. 4% of patients. The resection rate was 96.4%
      (complete macroscopic resection with histologic clear margins [R0], 83.6%;
      complete macroscopic resection with microscopic disease at the resection margin
      [R1], 1.8%; and macroscopic residual disease [R2], 10.9%). The operative
      mortality rate was 0%, whereas the hospital mortality was 7.3%. Twenty-three
      patients had a complete macroscopic response, 12 of whom (21.8%) had a complete
      histopathologic response. The tumor stages according to the American Joint
      Committee on Cancer staging system were pT0N0 in 12 patients, Stage 0 in 8
      patients, Stage IIa in 6 patients, Stage IIb in 6 patients, Stage III in 8
      patients, and Stage IV in 13 patients. Laryngeal preservation was achieved in 8
      of 12 patients in whom total pharyngolaryngoesophagectomy initially was indicated
      because of tumor response and an R0 resection. The overall survival rates at 1
      year, 3 years, and 5 years were 61%, 39%, and 33%, respectively, and the DFS
      rates were 49%, 32%, and 29%, respectively. The respective survival rates for
      responders were 82%, 58%, and 53%, and the DFS rates were 68%, 54%, and 48%.
      CONCLUSIONS: Neoadjuvant treatment is tolerated well by most patients.
      Combination therapy increases the resectability rate and facilitates laryngeal
      preservation. Significant improvements in the actuarial survival rate and the DFS
      rate were observed in the group of patients who achieved partial and complete
      responses.

PMID- 10964324
TI  - Mutation and expression of the metastasis suppressor gene KAI1 in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: KAI1/CD82, a tumor metastasis suppressor gene, is correlated
      inversely with the progression and invasion of several tumors. It also has been
      reported that the KAI1 gene is related to the tumor suppressor gene p53. This
      study was performed to clarify the correlation between KAI1/CD82 expression and
      clinicopathologic characteristics and p53 expression in patients with esophageal
      squamous cell carcinoma (ESCC). The authors also investigated mutation of the
      KAI1 gene coding region to determine whether this may reduce KAI1 expression in
      ESCC. METHODS: Using immunohistochemistry with anti-KAI1 polyclonal antibody and
      monoclonal antibody against p53, KAI1/CD82 and p53 expression were detected in 55
      patients with ESCC who had undergone surgery. The authors examined the KAI1 gene
      mutation in 22 patients with ESCC by polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. RESULTS:
      KAI1/CD82 expression was positive in 36 of 55 patients (65.5%). There was a
      significant inverse correlation between KAI1/CD82 expression and regional lymph
      node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of
      lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046). The
      survival rates of KAI1/CD82 negative patients were poorer than those of positive
      patients (P = 0. 024). The correlation between KAI1 positive and p53 positive
      tumors was not statistically significant. None of the 22 patients with ESCC
      showed mutation of the KAI1 gene by PCR-SSCP. In one patient, there was
      polymorphism in the SSCP assay and DNA sequencing. CONCLUSIONS: The authors
      demonstrated immunohistochemically that the expression of KAI1 protein appeared
      to be correlated with lymph node metastasis. Mutation does not seem to be a
      mechanism for dysregulation of the KAI1 protein in ESCC.

PMID- 10964325
TI  - A rare case of multiple carcinoids and endocrine cell micronests in a patient
      with chronic duodenitis.
AB  - BACKGROUND: To the authors' knowledge, multiple carcinoid tumors of the duodenum
      have not been reported previously. However, multiple carcinoids in the stomach,
      ileum, and rectum, which were accompanied by the proliferation of endocrine
      cells, have been reported in the published literature. METHODS: A patient with
      multiple carcinoids including argyrophilic cell hyperplasia of the duodenum and
      hypergastrinemia underwent surgery. The resected stomach and duodenum were
      analyzed histopathologically. RESULTS: There were 11 carcinoid lesions, each of
      which was accompanied by peripheral endocrine cell micronests (ECMs). Increasing
      gastrin positive cells in the antral region and chronic duodenitis in the
      duodenal bulb also were observed. The peripheral ECMs usually were adjacent to
      proliferating argyrophilic cells in the Brunner gland ducts or the crypts of
      Lieberkuhn, which showed focal pyloric gland metaplasia. CONCLUSIONS: In the case
      presented in the current study, the development of the multiple carcinoid lesions
      may be strongly related to the presence of multifocal pyloric gland metaplasia,
      as well as to the trophic action of gastrin, which is present at high levels in
      the setting of chronic duodenitis.

PMID- 10964326
TI  - Prognostic significance of reverse transcriptase-polymerase chain reaction
      measurement of carcinoembryonic antigen mRNA levels in tumor drainage blood and
      peripheral blood of patients with colorectal carcinoma.
AB  - BACKGROUND: The objective of this study was to assess the prognostic value of
      detecting circulating tumor cells in the tumor drainage blood and peripheral
      blood of patients with colorectal carcinoma. METHODS: A total of 53 patients with
      advanced colorectal carcinoma were studied. Tumor drainage blood and peripheral
      blood samples that were obtained during surgery were examined for
      carcinoembryonic antigen (CEA) mRNA using reverse transcriptase-polymerase chain
      reaction (RT-PCR). RESULTS: In spiking experiments, the assay indicated a
      sensitivity limit of 1 carcinoma cell per 10(6) cells. CEA mRNA was detected in
      the tumor drainage blood of 36 of 53 patients (68%) and in the peripheral blood
      of 18 of 53 patients (34%). The rate of detection in both tumor drainage blood
      and peripheral blood was significantly higher in patients with lymph node
      metastasis, lymphatic invasion, or vascular invasion (P < 0.05). Among those
      patients who underwent potentially curative resection, the 2-year disease free
      survival rate of patients whose tumor drainage or peripheral blood was negative
      for CEA mRNA was significantly better than that of patients who showed CEA mRNA
      positivity of either sample (tumor drainage blood: 100% vs. 57%; P < 0.05;
      peripheral blood: 74% vs. 50%; P < 0.01), although the follow-up thus far has
      been only 9-30 months. CONCLUSIONS: The presence of CEA mRNA in the blood is a
      useful indicator of circulating tumor cells, and it is one of the determinant
      prognostic factors for patients with colorectal carcinoma. Moreover, the absence
      of CEA mRNA in tumor drainage blood was found to be a superior marker for disease
      free survival compared with that in peripheral blood.

PMID- 10964327
TI  - Expression of transforming growth factor-alpha mRNA in livers of patients with
      chronic viral hepatitis and hepatocellular carcinoma.
AB  - BACKGROUND: Transforming growth factor-alpha (TGFalpha) is an important autocrine
      growth factor of hepatocytes. The authors evaluated the roles of TGFalpha in
      chronic viral hepatitis (CVH) and hepatocellular carcinoma (HCC). METHODS: The
      authors measured the amounts of TGFalpha mRNA in liver tissues from 18 patients
      with HCC, 31 patients with CVH, and 7 normal controls. " Hot-start" reverse
      transcription-polymerase chain reaction (RT-PCR) using oligo-dT and specific
      primers detected TGFalpha mRNA in total cellular RNA extracted from liver
      tissues. The levels of TGFalpha mRNA were determined by the end point titers of
      serial, two-fold dilutions of cDNA. The amounts of hepatitis B virus RNA (HBV
      RNA) in livers of patients with chronic hepatitis B also were measured by
      Northern blot hybridization. RESULTS: TGFalpha mRNA levels were extremely higher
      in patients with HCC compared with patients with CVH and normal controls, and the
      levels in patients with CVH also were elevated compared with normal controls. The
      levels of TGFalpha mRNA were overexpressed in the underlying livers of patients
      with HCC compared with patients with CVH, although they were lower than those
      found in HCC tissues. The levels of TGFalpha mRNA were higher in samples from
      patients with chronic hepatitis B than in samples from patients with chronic
      hepatitis C. The levels of TGFalpha mRNA were not correlated with serum alanine
      aminotransferase or HBV-RNA levels in liver tissues in patients with chronic
      hepatitis B. However, the expression of TGFalpha mRNA tended to be higher in the
      livers of patients with raised serum alpha-fetoprotein levels. CONCLUSIONS: The
      overexpression of TGFalpha mRNA in the liver seems to be associated with the
      regeneration of hepatocytes rather than hepatic necrosis or viral replication.
      Also, it may be related closely to the development or progression of HCC,
      especially in the livers of patients with chronic hepatitis B.

PMID- 10964328
TI  - Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel
      induced apoptosis in hepatoma cells and its correlation with reactive oxygen
      species.
AB  - BACKGROUND: Previously, the authors observed that paclitaxel treatment of
      hepatoma cells resulted in differential cytotoxicity. Whether other
      antimicrotubule agents (docetaxel and 2-methoxyestradiol) are more effective than
      paclitaxel is not clear. Moreover, whether the modulation of reactive oxygen
      species (ROS) is involved in the drug-induced growth inhibition of hepatoma cells
      is not known. METHODS: The authors examined the effects of 2-methoxyestradiol,
      paclitaxel, and docetaxel on HepG2, Hep3B, HA22T/VGH, and Hepa1-6 hepatoma cell
      lines. The parameters examined included cell viability, cell membrane
      permeability, cell cycle distribution, DNA fragmentation, and ROS generation.
      RESULTS: Docetaxel and paclitaxel inhibited the growth of hepatoma cells at
      submicromolar concentrations, whereas that of 2-methoxyestradiol was within a
      micromolar range. This drug-induced growth inhibition was cell cycle dependent. 2
      Methoxyestradiol-treated (10-50 microM) cells resulted in G2/M block prior to
      apoptosis. High dose (0.1 microM) docetaxel- and paclitaxel-treated cells
      resulted in a G2/M arrest followed by generation of polyploidy or apoptosis;
      however, low dose (0.01 microM) treatment induced apoptosis without G2/M arrest.
      The low dose effect was more significant in docetaxel-treated cells than in
      paclitaxel-treated cells. Although these antimicrotubule agents increased the
      formation of ROS, antioxidant treatment did not block drug-induced cell cycle and
      growth inhibition effects. CONCLUSIONS: The current results suggest that the
      growth inhibition of hepatoma cells induced by 2-methoxyestradiol, paclitaxel,
      and docetaxel was mediated through G2/M-phase arrest, caspase activation, and DNA
      fragmentation. The drug-induced apoptosis was independent of ROS formation.
      Docetaxel was more effective than paclitaxel in killing hepatoma cells. The
      potential of using 2-methoxyestradiol and docetaxel for the treatment of patients
      with hepatoma is worthy of further study.

PMID- 10964330
TI  - Suppression of proline-directed protein kinase F(A) expression potentiates
      erythroid differentiation of human myeloid leukemia cells.
AB  - BACKGROUND: Initial clinic studies revealed that the overexpression of proline
      directed protein kinase F(A) (PDPK F(A)) is associated conversely with various
      stages of tumor tissue differentiation. However, the role of overexpressed PDPK
      F(A) in tumor cell differentiation remains unknown and needs to be established.
      In this report, the authors explore the potential role of PDPK F(A) in cellular
      differentiation by investigating the effects of partial inhibition of this kinase
      on erythroid differentiation of chronic myeloid leukemia cells (K562). METHODS:
      PDPK F(A) antisense expression vector and its specific antibody were developed
      successfully. Two stable, transfected antisense clones of human myeloid leukemia
      cells were subcloned that expressed approximately 80% and approximately 50% of
      the total PDPK F(A) existing in control-transfected clones, as determined by both
      immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, the
      PDPK F(A) antisense clones expressed no significant suppression of any other
      related PDPK members' expression, demonstrating the specificity of these two
      antisense clones. RESULTS: The antisense clones proportionally induced
      spontaneous erythroid differentiation up to approximately 30% of the total K562
      cells. Moreover, antisense suppression of PDPK F(A) expression appeared to
      potentiate sodium butyrate/hemin-induced erythroid differentiation of K562 cells
      to a more complete stage compared with the control. CONCLUSIONS: The results
      demonstrate that specific antisense suppression of overexpressed PDPK F(A) in
      human myeloid leukemia cells is sufficient to potentiate both spontaneous and
      drug-induced erythroid differentiation, indicating that PDPK F(A) is an important
      negative regulator in controlling the erythroid differentiation of human myeloid
      leukemia cells.

PMID- 10964329
TI  - Overexpression of cathepsin B and urokinase plasminogen activator is associated
      with increased risk of recurrence and metastasis in patients with chondrosarcoma.
AB  - BACKGROUND: Deregulation of the cellular protease network has been shown to be
      responsible for aggressive clinical behavior in several common human
      malignancies. In the current study, the authors evaluated the expression patterns
      of proteases in patients with chondrosarcoma of bone and correlated these
      patterns with clinical outcome. METHODS: The expression levels of urokinase
      plasminogen activator; matrix metalloproteinase types-1, -2, and -9; and
      cathepsins B and L were determined immunohistochemically in 114 cases of
      chondrosarcomas of bone and were correlated with their clinicopathologic
      parameters as well as with long term follow-up data. RESULTS: Overexpression of
      cathepsin B was associated with a high rate of local recurrence (P = 0.006) and a
      decreased recurrence free survival (P = 0.005). Overexpression of urokinase
      plasminogen activator was associated with an increased rate of metastasis (P = 0.
      013), a decreased metastasis free survival (P = 0.016), and a decreased 5-year
      overall survival rate (P = 0.048). The univariate Cox model showed that tumor
      extension into soft tissue, high histologic grade, and overexpression of
      cathepsin B were predictors of adverse outcome. Multivariate analysis showed only
      overexpression of cathepsin B and tumor extension into soft tissue to be
      independent predictors of local recurrence. CONCLUSIONS: Overexpression of
      cathepsin B and urokinase plasminogen activator can be used to identify those
      patients with chondrosarcoma of bone who have an increased risk of local
      recurrence and distant metastases.

PMID- 10964331
TI  - Basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is characterized by marked interpatient
      variation in tumor accrual. The authors previously reported that presentation
      with a cluster of BCC is associated with an inherited predisposition to develop
      many additional lesions suggesting clustering is a critical event. A cluster is
      defined as the presence of two or more new, primary BCCs, at initial or later
      presentation. METHODS: The authors recruited 927 cases and determined whether 1)
      clustering was an early or late event and 2) tumor accrual was altered after
      clustering. RESULTS: In the cases, 669 patients developed only 1 lesion, 112
      patients presented more than once but with single lesions (single presentation
      phenotype[SPP]-more), 94 cases had a cluster at first presentation (multiple
      presentation phenotype [MPP]-cluster initial), and 52 cases first presented with
      1 lesion but later had a cluster (MPP-cluster later). The authors found that 1)
      clustering occurred relatively late. The mean ages at first presentation with 1
      BCC of the SPP-more (61.5 years) and MPP-cluster later patients (60.4 years) were
      similar although presentations with clusters in the MPP-cluster initial (67.6
      years, P = 0.0002) and -cluster later cases (68.1 years, P = 0.002) occurred
      significantly later. 2) Clustering was associated with increased accrual. Thus,
      26 patients (MPP-cluster later/a) in the MPP-cluster later group had a additional
      BCC postcluster. Mean accrual post-cluster (1.99 BCC/year) in these cases was
      significantly increased (P = 0.0001) compared with precluster accrual (0.39
      BCC/year). CONCLUSIONS: The authors found that the formation of BCC clusters
      represents a critical event such that after a cluster presentation, tumor accrual
      is significantly increased. Cluster presentation is a relatively late event
      suggesting reduced effectiveness in immune surveillance.

PMID- 10964332
TI  - Positron emission tomography scanning in malignant melanoma.
AB  - BACKGROUND: Several recent studies have demonstrated the low yield of
      anatomically based computed tomography scans in evaluating Stage III (American
      Joint Committee on Cancer) patients with malignant melanoma. The purpose of this
      study was to investigate the efficacy and clinical utility of functionally based
      positron emission tomography (PET) scans in the same patient population. METHODS:
      A prospective evaluation of 106 whole body PET scans obtained after injection of
      2-fluorine-18, 2-fluoro-2-deoxy-D-glucose (FDG) was performed in 95 patients with
      clinically evident Stage III lymph node and/or in-transit melanoma. Areas of
      abnormality on FDG PET scanning were identified visually as foci of increased
      metabolic activity compared with background, and all positive foci were assessed
      pathologically. RESULTS: In this patient population, there were 234 areas that
      were evaluated pathologically of which 165 were confirmed histologically to be
      melanoma. PET scanning identified 144 of the 165 areas of melanoma for a
      sensitivity of 87.3%. The 21 areas of melanoma that were missed included 10
      microscopic foci, 9 foci less than 1 cm, and 2 foci greater than 1 cm. There were
      39 areas of increased PET activity that were not associated with malignancy for a
      78.6% predictive value of a positive test. Of the 39 false-positive areas (false
      positive rate of 56.5%), 13 could be attributed to recent surgery, 3 to
      arthritis, 3 to infection, 2 to superficial phlebitis, 1 to a benign skin nevus,
      and 1 to a colonic polyp. Pathologic evaluation of the remaining false-positive
      areas failed to reveal a definitive etiology for their increased activity on PET
      scan. With the application of pertinent clinical information, the predictive
      value of a positive PET scan could be improved to 90. 6%. The specificity of PET
      scanning in this study was only 43.5% because very few prophylactic lymph node
      dissections were performed. Thirty-six of the total 183 abnormal areas (19.7%) on
      PET scanning proved to be unsuspected areas of metastatic disease. These findings
      led to a change in the planned clinical management in patients after 16 of the
      106 PET scans (15.1%). CONCLUSIONS: FDG PET scanning can be helpful in managing
      patients with Stage III melanoma in whom further surgery is contemplated.
      Although false-positive areas are not uncommon, PET scans did change the
      management of patients 15% of the time. PET's inability to identify microscopic
      disease suggests that it is of limited use in evaluating patients with Stage I-II
      disease.

PMID- 10964333
TI  - A psychosocial group intervention for Japanese women with primary breast
      carcinoma.
AB  - BACKGROUND: To the authors' knowledge, there had been no evidence for the
      efficacy of psychosocial intervention among Japanese cancer patients. The
      objective of this study was to determine the effect of a psychosocial group
      intervention in reducing psychologic distress and enhancing coping in this
      population in a randomized controlled trial. METHODS: The patient selection
      criteria were age younger than 65 years, lymph node metastasis positive and/or
      histologic or nuclear Grade 2-3, and surgery undergone within the previous 4-18
      months as of the start of the study. We conducted a 6-week, structured,
      psychosocial group intervention. The intervention consisted of health education,
      coping skills training, stress management, and psychologic support. Subjects were
      assessed for psychologic distress and coping by administering the Profile of Mood
      States (POMS), Mental Adjustment to Cancer (MAC) scale, and Hospital Anxiety and
      Depression (HADS) scale at the baseline, at 6 weeks, and at 6 months. RESULTS:
      Fifty (33%) of the 151 patients participated and were randomized, and 46 (30%)
      completed the study. The experimental group had significantly lower scores than
      the controls for total mood disturbance and significantly higher scores for vigor
      on the POMS, and significantly higher scores for fighting spirit on the MAC at
      the end of the 6-week intervention. These improvements were sustained over 6
      months of follow-up. CONCLUSIONS: The results of this study suggest that a short
      term psychosocial group intervention produces significant long term improvement
      in the quality of life of Japanese patients with primary breast carcinoma.

PMID- 10964334
TI  - Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin
      (Doxil) in metastatic breast carcinoma.
AB  - BACKGROUND: Doxil (ALZA Corp., Mountain View, CA) is a formulation of doxorubicin
      in polyethylene-glycol coated liposomes with a prolonged circulation time and
      unique toxicity profile. As yet, the effect of the dose schedule on toxicity and
      the correlation of toxicity with pharmacokinetics have not been directly
      addressed. METHODS: The objectives of this study were to examine the toxicity
      profile and pharmacokinetics of various dose schedules of Doxil in a group of
      patients with metastatic breast carcinoma (MBC) previously treated with
      chemotherapy. Forty-five patients received a total of 268 courses of Doxil
      (median per patient, 5; range, 1-19). Six dose schedules were investigated: 35
      mg/m2 every 3 weeks (11 patients), 45 mg/m(2) every 3 weeks (5 patients), 50
      mg/m(2) every 4 weeks (5 patients), 60 mg/m(2) every 4 weeks (6 patients), 65
      mg/m(2) every 5 weeks (6 patients), and 70 mg/m(2) every 6 weeks (12 patients).
      Doxil pharmacokinetics was examined in 24 of these patients at the dose levels of
      35, 45, 60, and 70 mg/m(2). RESULTS: Stomatitis was dose related, with higher
      incidence and severity at doses of 60-70 mg/m(2). Skin toxicity in the form of
      palmar-plantar erythrodysesthesia (PPE) developed usually after two or more
      courses of treatment and was schedule dependent with shorter dosing intervals
      leading to increased frequency and severity of skin manifestations.
      Myelosuppression, mainly as leukopenia/neutropenia, was dose dependent but mild
      and uncomplicated in most cases. Hair loss was infrequent (< 7%) and always of
      limited extent. Despite high cumulative doses up to 1500 mg/m(2), cardiac
      toxicity was observed in only 1 patient who received prior mitoxantrone and
      mediastinal radiotherapy. Objective responses, improvements, and durable
      stabilizations were observed in 9, 6, and 14 patients, respectively, indicating
      significant antitumor activity of Doxil in previously treated MBC patients. Doxil
      pharmacokinetics was well described by a monoexponential elimination curve with a
      long T(1/2) (median, 79 hours), a slow clearance (median, 40 mL/hour), and a
      small volume of distribution (median, 3.9 L). Cmax (peak plasma concentration)
      and AUC (area under the concentration*time curve) increased linearly with dose
      with a statistically significant correlation. Correlation analysis of dose and
      pharmacokinetic parameters with Doxil toxicites revealed that stomatitis grade
      and leukocyte nadir were correlated strongly with dose and Cmax, and weakly with
      AUC, whereas PPE grade was correlated significantly with only 1 parameter,
      T(1/2). CONCLUSIONS: The toxicity of Doxil is dose and schedule dependent and
      well correlated with pharmacokinetic parameters. Pharmacokinetic guidance of
      Doxil dosing may be a useful tool.

PMID- 10964335
TI  - Early invasive adenocarcinoma of the cervix.
AB  - BACKGROUND: Adenocarcinoma of the cervix is increasing in frequency. There is a
      dearth of specific detail concerning the histomorphology, histogenesis, and
      associated findings in early invasive cervical adenocarcinoma. METHODS: Forty
      cases of cervical adenocarcinoma invasive to 5 mm or less were examined in
      detail. RESULTS: Mean patient age was 40.9 years. In 78% of the cases, the
      midpoint of the invasive focus was in the region of the squamocolumnar junction
      or transformation zone; more than 1 invasive focus was present in 4 cases. Eighty
      five percent of cases also had adenocarcinoma in situ (AIS). In 9 of 10 minimally
      invasive cases, small invasive glands were present in the stroma adjacent to AIS.
      In some of these, the AIS had preinvasive buds that were still attached.
      Endometrioid adenocarcinomas were associated with AIS but were located higher in
      the canal than the more common endocervical type. All three adenosquamous
      carcinomas were associated with both squamous intraepithelial neoplasia and AIS.
      Vascular space invasion was observed in two cases, microglandular hyperplasia in
      four. CONCLUSIONS: Adenocarcinoma in situ is the precursor to most
      adenocarcinomas of the cervix with an average interval between clinically
      detected AIS and early invasion of approximately 5 years, supporting the
      potential for Papanicolaou test screening to prevent this disease. However, the
      existence of small carcinomas in the absence of AIS suggests the possibility of
      rapid progression in some cases. Invasion occurs by budding from or expansion of
      AIS glands, usually in the region of the squamocolumnar junction. Multifocal
      invasion is uncommon, as is vascular invasion in early lesions. The endometrioid
      variant has the same histogenesis as the endocervical type but may arise higher
      in the canal. The precursor of adenosquamous carcinoma has a similar bimorphic
      differentiation potential. Microglandular hyperplasia is not related to early
      invasive adenocarcinoma.

PMID- 10964336
TI  - Assessment of morphometric measurements of prostate carcinoma volume.
AB  - BACKGROUND: The authors have shown that the primary determinants of prostate
      carcinoma progression are tumor volume and the percent of the tumor comprised of
      Gleason Grade 4/5 cells. In the current study the authors evaluated six different
      techniques for the morphometric measurements of prostate carcinoma volume.
      METHODS: A computer-assisted image analysis (NIH Image, developed and maintained
      by the National Institutes of Health, Bethesda, MD) was used to analyze all 108
      step-sectioned prostate specimens obtained between January 1 and December 31,
      1997. The authors used the Stanford technique of 0.3-cm step-sections, measuring
      the volume of the tumor at both 0.3-cm and 0.6-cm intervals. The other 4 methods
      included the authors' previous method based on an earlier image program, the
      ellipsoidal method (pi / 6 x width x height x length), an estimation of the
      square area of the largest tumor, and the maximum tumor dimension (MTD). RESULTS:
      The authors first checked the accuracy of NIH Image analysis by measuring 24
      circles of widely different sizes. The mean coefficient of variation was 1.7% and
      the correlation between the mean circle areas measured by the NIH Image software
      and true circle area essentially was perfect (correlation coefficient [r] = 1 and
      r(2) = 0.999; P < 0.0001). In comparison with the authors' original computer
      image program using 0.3-cm step-sections measured by a different observer, r(2)
      with the NIH Image analysis was 0.93. Using NIH Image only, the 0.6-cm step
      section method missed measurable cancers in 16.7% of 108 radical prostatectomies
      in comparison with the 0.3-cm step-method. The mean tumor volume with the 0.6-cm
      section method (P < 0.0001) and the ellipsoidal method (P < 0.05) were
      significantly higher than with the 0.3-cm section method. r(2) from linear
      regressions using the 0.3-cm step section method as the standard versus the
      ellipsoidal method was 0.594, and was 0.89 versus the 0.6-cm step-section method,
      0.652 versus the square area estimation, and 0. 527 versus the MTD method.
      CONCLUSIONS: The results of the current study support NIH Image as a powerful
      software program for the morphometric measurement of prostate carcinoma volume.
      Pathologic processing with 0.3-cm section slices was found to be more accurate
      for tumor volume than the 0.6-cm section slices. The ellipsoidal method, the
      square area of the largest tumor, and the MTD all were found to be inferior to
      computer-assisted image analysis measurements. In certain clinical situations in
      which only estimates of tumor volume are required, the square area of the largest
      tumor appears to be the best choice (r(2) 0.652).

PMID- 10964337
TI  - Nuclear DNA content-derived parameters correlated with heterogeneous expression
      of p53 and bcl-2 proteins in clear cell renal carcinomas.
AB  - BACKGROUND: p53 and bcl-2 are two key genes involved in cell cycle and cell death
      regulation. Altered expression or mutation of these genes has been found in human
      cancers and also has been identified in clear cell renal carcinoma (RCC). Their
      role in RCC progression, however, is still unclear. By contrast, the prognostic
      significance of ploidy and S-phase fraction (SPF) have been studied extensively
      in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in
      RCC, we offer a multisample correlative analysis of the expression of these two
      proteins with ploidy and SPF. METHODS: Ploidy and SPF along with p53 and bcl-2
      expression were analyzed in 296 specimens, selected by multiple sampling of 33
      consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied
      by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry.
      RESULTS: In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32
      (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of
      28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32
      (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P =
      0. 03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein
      expression. Expression of p53 protein correlated with the lack of bcl-2 protein
      expression (P = 0.0032), aneuploidy (P < 0. 0001), and high SPF (P = 0.0006),
      whereas bcl-2 expression was associated with a normal DNA content (P < 0.0001)
      and low SPF (P = 0. 035). CONCLUSIONS: Within each RCC, p53 and bcl-2 expression
      is markedly heterogeneous. Our results depicted a scenario in which bcl-2
      protein, expressed by normal renal parenchyma, is still present in euploid cell
      clones of RCC but disappears during the progression of renal neoplasm toward a
      more aggressive phenotype characterized by overexpression of p53 protein,
      aneuploidy, and high SPF.

PMID- 10964338
TI  - Renal cell carcinoma to the pancreas in surgical pathology material.
AB  - BACKGROUND: Clear cell carcinomas of the pancreas are rare and more likely
      represent metastatic renal cell carcinoma (RCC). METHODS: Twenty-one cases of
      metastatic RCC to the pancreas were retrieved from the files of the Endocrine
      Registry of the Armed Forces Institute of Pathology. Histologic features were
      reviewed, special stains and immunohistochemical studies were performed, and
      patient follow-up data were obtained. RESULTS: The patients included 9 women and
      12 men ages 47-76 years (mean, 64.4 years). Patients experienced weight loss,
      abdominal pain, or a mass lesion. The tumors occurred anywhere within the
      pancreas. The mean size of the tumors was 4.0 cm. Histologically, the tumors were
      comprised of clear cells with a rich vascular network. The RCC was diagnosed
      before (n = 17 patients; ages up to 32.7 years) or after (n = 4 patients; ages up
      to 13.2 years) the pancreatic metastases were discovered. Surgery was used in all
      patients. Adjuvant chemotherapy was used in 4 patients. From the date of the
      diagnosis of pancreatic metastasis, 13 patients were dead with disseminated
      disease (DD) (mean, 4.5 years), and 8 patients were without disease (mean, 9.0
      years). From the date of the diagnosis of primary RCC, 13 patients were DD (mean,
      12.7 years), and 8 patients were without disease (mean, 24.7 years). CONCLUSIONS:
      Although histochemical and immunohistochemical studies may help in the
      distinction between patients with primary versus metastatic clear cell tumors of
      the pancreas, clinical confirmation should be obtained. Surgical resection of the
      pancreatic metastatic disease is suggested, because the patient may still have a
      prolonged survival.

PMID- 10964339
TI  - Long term follow-up of combined radiochemotherapy for locally advanced bladder
      carcinoma.
AB  - BACKGROUND: The 5- and 10-year survival rates and the toxicity of combined
      radiochemotherapy for 53 consecutive patients with locally advanced bladder
      carcinoma were studied in a noncomparative trial. METHODS: Between November 1986
      and October 1987, 53 consecutive patients (mean age, 68 years) with muscle
      invasive and/or locally advanced bladder carcinoma were treated by simultaneous
      chemotherapy and hyperfractionated irradiation. Radiation was administered during
      the first to fourth week and during the ninth to tenth week as an interrupted
      treatment protocol. Cisplatin and epirubicin were used as radiosensitizers before
      radiation. The maximum dose of irradiation was 57.6 grays. RESULTS: Of 53
      patients, 45 completed the planned treatment course. Causes for discontinuing
      therapy in 8 patients were pronounced myelosuppression (n = 2), severe
      gastrointestinal symptoms (n = 2), nephrotoxicity (n = 1), and severe
      radioproctitis (n = 1). Two additional patients stopped therapy due to vascular
      diseases independent of treatment-related toxicity. The overall survival for all
      53 patients was 23% after 5 years and 8% after 10 years. Cause specific survival
      was 36% after 5 years and 29% after 10 years. Four patients are still alive after
      10 years without disease progression. One of them received incomplete therapy due
      to toxicity. All four patients underwent transurethral resections for
      superficial, local tumor recurrences. CONCLUSIONS: The poor prognosis group of
      patients with invasive and/or locally advanced bladder carcinoma was found to
      have a limited disease specific survival after combined radiochemotherapy.

PMID- 10964340
TI  - Brain metastases in patients with no known primary tumor.
AB  - BACKGROUND: The care of patients with a brain metastasis from unknown primary
      site is controversial. The authors reviewed the results of stereotactic
      radiosurgery in this group of patients to better define clinical expectations.
      METHODS: During an 11-year interval, radiosurgery was performed in 421 patients
      with brain metastases at the University of Pittsburgh. Fifteen patients had
      solitary or multiple (< or = 5) brain metastases without a detectable primary
      site at the time of initial presentation. In five patients, a histologic
      diagnosis of cancer was obtained from extracranial metastatic sites. In 10
      patients, a diagnosis was obtained from the brain. A total of 31 tumors with a
      mean volume of 4.3 mL (range, 0. 05-18.6 mL) underwent radiosurgery with a mean
      marginal dose of 16.2 Gray (Gy) (range, 12-20 Gy). Fourteen patients (93.3%) also
      received whole brain fractionated radiation therapy. RESULTS: The median survival
      was 15 months after radiosurgery (range, 1-48 months) and 27 months after their
      initial diagnosis of cancer. In 4 patients (26. 7%), the primary tumor was
      discovered later (lung in 3 patients and liver in 1). Three of these four
      patients died due to progression of their primary tumor. Of the remaining 11
      patients, 4 died of progression of extracranial metastases, 2 died of other
      systemic diseases, and 3 patients died because of progression of brain
      metastasis. Three patients (20%) were still living between 21-48 months after
      radiosurgery. The presence of active systemic disease and brain stem location
      both were associated with a poor outcome (P = 0.004 and 0.04). The actuarial
      imaging-defined local tumor control rate was 91.3 +/- 5.9% at 4 years.
      CONCLUSIONS: Radiosurgery was an effective strategy for patients with brain
      metastases from an unknown primary site. Disease progression outside of the brain
      was the usual cause for patient death.

PMID- 10964341
TI  - Recurrence of meningiomas.
AB  - BACKGROUND: Macroscopic total resection with removal of involved dura and bone
      does not always prevent the recurrence of meningioma of histologically benign
      subtype. Many causative factors have been investigated, although the mechanism of
      recurrence remains unclear. Vascular endothelial growth factor (VEGF) is a key
      factor in meningiomas neovascularization, and the authors investigated whether
      VEGF expression can predict the recurrence of histologically benign meningiomas
      after macroscopic total resection. METHODS: Fifty-four patients with
      supratentorial convexity meningiomas were investigated at least 3 years after
      surgery or until tumor recurrence to clarify risk factors for recurrence.
      Patients were restricted to Simpson Grade 1 resection only, and the authors
      excluded multiple meningiomas, neurofibromatosis, and atypical and anaplastic
      meningiomas. Correlation between recurrence and the following factors were
      statistically analyzed: age, gender, tumor volume, tumor shape, bone change,
      brain edema, vascular supply, histologic subtype, MIB-1 labeling index (LI), and
      VEGF expression. RESULTS: Of the 54 patients with meningioma, 34 were positive
      (24: +1; 10: +2) for VEGF, and 20 were negative. Six (11.1%) meningiomas recurred
      during the follow-up period. Multivariate analysis revealed that high levels of
      expression of VEGF constituted the most useful predictor of recurrence (P =
      0.005), followed by high MIB-1 LI (P = 0.039). The other factors were not
      significant. The tumor recurrence, when it occurred, was within the brain and not
      durally based. CONCLUSIONS: The current results suggest that high levels of VEGF
      expression are significantly related to the recurrence of meningioma. VEGF
      secretion from microscopic residue remaining after surgery may induce
      neovascularization, which promotes the recurrence of meningioma.

PMID- 10964342
TI  - Benign central neurocytoma.
AB  - BACKGROUND: "Central neurocytoma" is classically considered as an
      intraventricular benign tumor, largely based on data from small retrospective
      series. The authors present prospective data on 12 patients with tumors diagnosed
      as central neurocytoma, to highlight the diverse nature of this tumor and
      challenge the classic notion. METHODS: Between 1991 and 1997, 12 patients had
      tumors diagnosed prospectively as "central neurocytoma". Clinical, radiologic,
      and histologic data were collected, and Karnofsky performance score was evaluated
      for each patient. Proliferation marker studies were performed using Ki-67
      labeling index. RESULTS: In two patients, the tumors were located in atypical
      locations, namely, the parietal lobe and the spine. Aggressive behavior
      characterized by clinical and radiologic evidence of tumor progression was noted
      in two additional patients. In both these cases, unusually high proliferation
      rates of 5.3% and 11.2% were noted. Total excision of the tumor, when possible,
      was the treatment of choice. Postoperative radiotherapy to the residual tumor may
      be of benefit in patients with clinically aggressive tumors, or those with high
      proliferation rates. CONCLUSIONS: Given the findings of this study, it is
      suggested that the traditional concept of central neurocytoma as a benign
      intraventricular tumor warrants reconsideration.

PMID- 10964343
TI  - Cancer in the very elderly Dutch population.
AB  - BACKGROUND: Cancer incidence and mortality rates rarely are studied in people age
      > 85 years. Usually, patients ages 65 years, 75 years, and 85 years of age are
      combined into 1 group because of small numbers. The number of people age > or =
      85 years in the Netherlands increased from 99,000 in 1976 to 203,000 in 1995 (an
      increase of 105%). The growth of the total population in this period was only
      13%. This study addressed cancer incidence and mortality rates among the very
      elderly in the Netherlands. METHODS: Cancer mortality data (1976-1995) and
      population data were obtained from Statistics Netherlands, whereas cancer
      incidence data (1989-1995) were provided by the Netherlands Cancer Registry.
      Cancer incidence and mortality rates were calculated and trends in cancer
      mortality were studied. RESULTS: Total cancer incidence rates were highest in the
      age group 85-94 years, in men and women (3466/100,000 person-years and
      1604/100,000 person-years, respectively). Prostate carcinoma was the most
      frequent cancer in men ages 85-94 years, followed by colorectal carcinoma. In
      women ages 85-94 years, colorectal carcinoma was most frequent, closely followed
      by breast carcinoma. In the 95+ years age group squamous cell skin carcinoma was
      the most frequent cancer in both men and women, followed by prostate carcinoma in
      men and breast carcinoma in women. Cancer mortality rates increased with
      increasing age to nearly 3700/100,000 person-years in men age 95+ years and
      2500/100,000 person-years in women age 95+ years. In men, lung carcinoma was the
      most frequent cancer-related cause of death in patients age < or = 85 years,
      whereas in older men this applied to prostate carcinoma. In women, breast
      carcinoma was the most frequent cancer-related cause of death in all age groups >
      55 years. Cancer as a cause of death became less prominent with increasing age.
      Over the period 1991-1995, 42% of deaths in men ages 55-64 years were attributed
      to cancer versus 52% of deaths in women (total population); these proportions in
      the 95+ years age group were 11% and 7%, respectively. CONCLUSIONS: Peak
      incidence rates of major cancers were found in the very elderly population in the
      Netherlands. Different trends in age specific mortality rates of individual
      cancer sites were found, with stable rates in the middle age groups and
      increasing rates in the oldest age groups. This may reflect a real increase
      caused for instance by changes in mortality from other diseases and/or an
      artifactual increase caused by increased cancer detection rates in the (very)
      elderly.

PMID- 10964345
TI  - Impact of delirium on the short term prognosis of advanced cancer patients.
      Italian Multicenter Study Group on Palliative Care.
AB  - BACKGROUND: The objective of this study was to evaluate the impact of delirium on
      the survival of advanced cancer patients also assessed with a validated
      prognostic score (the palliative prognostic [PaP] score). METHODS: The study
      population was a prospective multicenter consecutive case series of advanced
      cancer patients for whom chemotherapy was no longer considered viable and who
      were referred to palliative care programs. Clinical and biologic prognostic
      factors included in the PaP score were assessed at study entry. The Confusion
      Assessment Method criteria were applied to screen patients presenting with
      delirium. Survival times were measured from time of enrollment and death taken as
      an outcome. Survival curves were traced with the Kaplan-Meier method and
      comparison were based on log rank tests. RESULTS: Delirium was found in 109 cases
      among 393 consecutive patients (27.7%). The diagnosis of delirium was
      independently associated with male gender, central nervous system metastases,
      lower performance status, worse clinical prediction of survival, and
      progestational treatment. The survival curve of patients with delirium was
      significantly different from the nondelirious patients curve (log rank, 31.6, P <
      0.0001). The median survival time was 21 days (95% confidence interval [CI], 16
      27) for the delirious patients and 39 days (95% CI 33-49) for the others.
      Multivariate analysis showed that the diagnosis of delirium and PaP score were
      independently associated with prognosis. CONCLUSIONS: The diagnosis of delirium
      significantly worsens life expectancy prognosticated with the PaP score. By using
      the PaP score together with the assessment of cognitive status, physicians can
      correctly predict patients 30-day survival in greater than 70% of cases.

PMID- 10964344
TI  - Noninvasive localization of tumors by immunofluorescence imaging using a single
      chain Fv fragment of a human monoclonal antibody with broad cancer specificity.
AB  - BACKGROUND: A single chain antibody fragment, NovoMAb-G2-scFv, derived from a
      human anti-tumor monoclonal antibody recognizes tumor antigen molecules expressed
      on a wide variety of human cancers including melanoma, breast carcinoma, colon
      adenocarcinoma, squamous cell carcinoma, lung carcinoma, and prostate carcinoma.
      This study was designed to evaluate the use of a NovoMab-G2-scFv/cyanine
      fluorochrome (Cy5.5.18) conjugate as diagnostic tool for in vivo imaging of
      tumors. METHODS: The NovoMab-G2-scFv-Cy5 complex was administered to athymic mice
      injected subcutaneously with human melanoma tumor cells, and the distribution of
      fluorescence was imaged noninvasively using a charge-coupled device camera.
      Images were acquired 2, 6, 12, 24, 48, and 72 hours after injection. RESULTS:
      Fluorescence was detected at the tumor site after injection of NovoMab-G2-scFv
      Cy5 but not after injection of a labeled irrelevant control antibody fragment.
      Fluorescence from the tumor site peaked 2 hours after injection and gradually
      declined, reaching a minimum 72 hours after injection. Fluorescence was also
      apparent in the kidneys, indicating clearance of the complex through the kidneys.
      Results suggest that 16% and 73% of the antibody is located in the tumor and
      kidneys, respectively. Imaging of isolated organs confirmed the presence of the
      NovoMab-G2-scFv-Cy5 complex in tumors, kidneys, and liver. No fluorescence was
      observed in other organs. CONCLUSIONS: Specific binding of the antibody-dye
      complex to the tumor was observed, and the kinetics of binding to tumors and
      kidneys were determined. These results suggest that the NovoMab-G2-scFv-Cy5.5
      complex may be used for noninvasive tumor localization.

PMID- 10964346
TI  - Histopathology defines prognostic subsets of ganglioneuroblastoma, nodular.
AB  - BACKGROUND: Ganglioneuroblastoma, nodular (GNBn) is a rare subtype of the family
      of neuroblastic tumors (neuroblastoma, ganglioneuroblastoma, and ganglioneuroma)
      that are classified in the unfavorable histology group according to the
      International Neuroblastoma Pathology Classification (Shimada system). Tumors of
      this subtype have been considered to represent a prototypic example of
      biologically and clinically nonaggressive (Schwannian stroma-rich and stroma
      dominant) components combined with biologically and clinically aggressive nodular
      (Schwannian stroma-poor) components. However, detailed histopathologic analysis
      as well as thorough prognostic evaluation of patients with this subtype has not
      been reported. METHODS: Pathology slides and reports from a total of 70 GNBn
      patients from the Children's Cancer Group (CCG)-3881 and CCG-3891 studies were
      reviewed. Sixty-eight tumors were classified in the favorable subset (FS) or the
      unfavorable subset (US) based on the evaluation of nodular components by applying
      the same histopathologic criteria (patient age, grade of neuroblastic
      differentiation, mitosis-karyorrhexis index) that are used for neuroblastomas in
      the International Neuroblastoma Pathology Classification. Patient prognosis as
      well as clinical and biologic characteristics within the subsets were analyzed,
      and the results were compared with those from 654 non-GNBn patients who were
      enrolled in the same CCG studies during the same period. RESULTS: Patients with
      GNBn tumors, usually diagnosed at age > 1 year, had a significantly lower overall
      5-year event free survival (EFS) rate than patients with non-GNBn subtypes (44.7%
      EFS vs. 65.0% EFS; P = 0. 0073). A significant difference in the outcome of the
      patients between the FS (22 patients; 86.1% EFS; 95.0% survival rate) and the US
      (46 patients; 29.0% EFS; 40.7% survival rate) of the GNBn subtype (P < 0.0005)
      was shown. When the cohort of patients with GNBn tumors was subdivided into FS
      and US, the outcomes were similar to those of patients with tumors of favorable
      histology (397 patients; 90.5% EFS; 97.6% survival rate) and with tumors of
      unfavorable histology (257 patients; 27.0% EFS; 35.7% survival rate) of the non
      GNBn type. The patients with US tumors frequently (63.0%) presented with distant
      metastasis. CONCLUSIONS: The current study demonstrates that the nodular
      components in GNBn tumors are not always aggressive. The prognosis of these
      patients can be determined by the analysis of age-linked histopathologic
      features.

PMID- 10964348
TI  - Depression after successful treatment for nonsmall cell lung carcinoma.
AB  - BACKGROUND: There have been few studies of depression in nonsmall cell lung
      carcinoma (NSCLC) patients after successful treatment. The purpose of the study
      was to clarify the prevalence and the correlated factors of depression after
      surgery. METHODS: A structured interview was conducted for patient
      characteristics and social support with NSCLC patients at baseline. One-month
      prevalence of depression at 1 and 3 months after surgery was obtained by follow
      up interviews at 1 and 3 months after surgery, respectively, whereas that of
      depression at 2 months after surgery was by the latter interview retrospectively.
      Three-month prevalence of depression was determined as presence of depression
      during any month in of a period of 3 months after surgery. A logistic analysis
      was used to examine the correlated factors of depression during the 3 months
      after surgery. RESULTS: Of 223 consecutive cancer patients who participated in
      the study between June 1996 and April 1999, 33 (14.8%) met the criteria for major
      or minor depression during the 3 months after surgery. One-month prevalence of
      depression at 1, 2, and 3 months after surgery were 9.0%, 9.4%, and 5.8%,
      respectively. The results of logistic regression analysis revealed that only
      satisfaction with confidants before surgery, of patient characteristics and
      social support factors, was significantly associated with depression during the 3
      months after surgery. CONCLUSIONS: These results suggest that depression is not
      rare after successful treatment for NSCLC and that social support may play an
      important role for NSCLC patients with depression after successful treatment.

PMID- 10964347
TI  - The memorial symptom assessment scale short form (MSAS-SF).
AB  - BACKGROUND: The Memorial Symptom Assessment Scale Short Form (MSAS-SF), an
      abbreviated version of the Memorial Symptom Assessment Scale, measures each of 32
      symptoms with respect to distress or frequency alone. A physical symptom subscale
      (PHYS), psychologic symptom subscale (PSYCH), and global distress index (GDI) can
      be derived from the Short Form. We validated the MSAS-SF in a population of
      cancer patients. METHODS: Two hundred ninety-nine cancer patients examined at the
      Section of Hematology/Oncology completed the MSAS-SF and the Functional
      Assessment Cancer Therapy (FACT-G). The Karnofsky performance status (KPS),
      extent of disease (EOD), and demographic data were assessed. The Cronbach alpha
      coefficient was used to assess internal reliability. MSAS-SF subscales were
      assessed against subscales of the FACT-G, the KPS, and EOD to determine criterion
      validity. Test-retest analysis was performed at 1 day and at 1 week. RESULTS: The
      Cronbach alpha coefficients for the MSAS-SF subscales ranged from 0.76 to 0.87.
      The MSAS-SF subscales showed convergent validity with FACT subscales. Correlation
      coefficients were -0.74 (P < 0.001) for the PHYS and FACT-G physical well-being
      subscales, -0.68 (P < 0.001) for the PSYCH and FACT emotional well-being
      subscales, and -0.70 (P < 0.001) for GDI and FACT summary of quality-of-life
      subscales. The MSAS-SF subscales demonstrated convergent validity with
      performance status, inpatient status, and extent of disease. The test-retest
      correlation coefficients for the MSAS-SF subscales ranged from 0.86 to 0.94 at 1
      day and from 0.40 to 0.84 for the 1 week group. CONCLUSIONS: The MSAS-SF is a
      valid and easy to use instrument for symptom assessment.

PMID- 10964350
TI  - Dienophilic behavior of the vinylic (C=C) and the carbonyl (C=O) bonds of ketenes
      in reactions with 1,3-diazabuta-1,3-dienes.
AB  - [reaction: see text] Ab initio and density functional studies (DFT) on
      cycloaddition reactions of 1,3-diazabuta-1,3-dienes with ketenes are reported.
      The vinylic (C=C) and the carbonyl (C=O) units of the ketenes are found to
      participate in concerted asynchronous [4 + 2] cycloaddition reactions. The
      transition states (3t, 4t, and 7t) for these paths have been located on the PE
      surface at the correlated levels of ab initio calculations. A reasonable
      mechanism for the formation of [4 + 2] and [2 + 2] adducts is presented.

PMID- 10964349
TI  - Virtual tape measure for the operating microscope: system specifications and
      performance evaluation.
AB  - OBJECTIVE: The Virtual Tape Measure for the Operating Microscope (VTMOM) was
      created to assist surgeons in making accurate 3D measurements of anatomical
      structures seen in the surgical field under the operating microscope. The VTMOM
      employs augmented reality techniques by combining stereoscopic video images with
      stereoscopic computer graphics, and functions by relying on an operator's ability
      to align a 3D graphic pointer, which serves as the end-point of the virtual tape
      measure, with designated locations on the anatomical structure being measured.
      The VTMOM was evaluated for its baseline and application performances as well as
      its application efficacy. METHODS: Baseline performance was determined by
      measuring the mean error (bias) and standard deviation of error (imprecision) in
      measurements of non-anatomical objects. Application performance was determined by
      comparing the error in measuring the dimensions of aneurysm models with and
      without the VTMOM. Application efficacy was determined by comparing the error in
      selecting the appropriate aneurysm clip size with and without the VTMOM. RESULTS:
      Baseline performance indicated a bias of 0.3 mm and an imprecision of 0.6 mm.
      Application bias was 3.8 mm and imprecision was 2.8 mm for aneurysm diameter. The
      VTMOM did not improve aneurysm clip size selection accuracy. DISCUSSION AND
      CONCLUSION: The VTMOM is a potentially accurate tool for use under the operating
      microscope. However, its performance when measuring anatomical objects is highly
      dependent on complex visual features of the object surfaces.

PMID- 10964351
TI  - A two-component pericyclic reaction for synthesis of substituted benzofurans and
      aryl-quaternary carbon bonds.
AB  - The reaction shown is presumed to be a new [3,3]-sigmatropic rearrangement
      involving an O-arylsulfoxonium species or related sulfurane. It allows a
      sulfoxide and a phenol to be joined and rearranged in one operation at or below
      room temperature, coupling an aromatic to a quaternary carbon and creating
      benzofurans or articulated dihydrobenzofurans in a number of examples.

PMID- 10964352
TI  - Silicon migration from oxygen to carbon and decarbonylation in
      methoxytriphenylsiloxycarbene.
AB  - [reaction: see text] Thermolysis of 2-methoxy-2-triphenylsiloxy-5,5-dimethyl
      Delta(3)-1,3, 4-oxadiazoline affords methyl triphenylsilylformate and methyl
      triphenylsilyl ether via methoxytriphenylsiloxycarbene. Kinetics show that the
      carbene undergoes reversible 1,2-triphenylsilyl migration (Brook rearrangement)
      as well as irreversible decarbonylation. Computed transition states and
      activation energies (B3LYP/6-31+G) suggest that the migration of the silyl group
      from oxygen to carbon occurs through an "in plane" transition state with the
      carbene lone pair forming a new bond to silicon. Decarbonylation involves a four
      membered ring, achieved by nucleophilic attack of the oxygen atom of the methoxy
      group at silicon.

PMID- 10964353
TI  - Transannular Diels-Alder studies on the asymmetric total synthesis of chatancin:
      the pyranophane approach.
AB  - [reaction: see text] A pathway is proposed for the biosynthesis of (+)-chatancin
      and (+)-sarcophytin linking these tetracycles to cembranoids by a pyranophane
      transannular Diels-Alder reaction. Preliminary synthetic results in this
      direction to reach macrocyclic dienedione 28 from farnesol are reported. Major
      synthetic steps include a Prins reaction, two enantioselective hydrogenations,
      and a macrocyclization via a beta-ketosulfoxide Michael-addition on an enone.

PMID- 10964354
TI  - Synthesis, cyclic voltammetry, and photophysical properties of a bridged o
      phenylenediamine-C(60) dyad.
AB  - The synthesis, complete spectroscopic characterization, cyclic voltammetry, and
      photophysical measurements of a new o-phenylenediamine-C(60) dyad are described.
      By using a tether strategy, only a single regioisomer was obtained. Cyclic
      voltammetry measurements indicate that the two electroactive groups do not
      interact in their singlet ground states. Photophysical investigations reveal a
      rapid photoinduced electron transfer between the singlet excited state of the
      fullerene acceptor and the o-phenylenediamine donor, yielding a charge-separated
      radical pair.

PMID- 10964356
TI  - Novel synthesis of photochromic polymers via ROMP.
AB  - [reaction: see text] Ring-opening metathesis polymerization (ROMP) of a
      photochromic 1, 2-bis(3-thienyl)cyclopentene monomer generated a series of novel
      polymers. All polymers exhibit reversible light-activated interconversion between
      their colorless-open and their colored-closed forms.

PMID- 10964355
TI  - Organometallic photonucleases: synthesis and DNA-cleavage studies of
      cyclopentadienyl metal-substituted dendrimers designed to increase double-strand
      scission.
AB  - [reaction: see text] A series of metal complex-substituted polyamine dendrimers
      have been synthesized and examined for their ability to cleave plasmid DNA in a
      double-stranded manner. While photolysis of the dimetallic spermine derivative
      and the tetrametallic DAB-Am-4 complex led to double-strand scission, in the
      larger DAB-Am-8 and DAB-Am-16 systems, DNA aggregation/precipitation was the
      predominant competing process observed.

PMID- 10964357
TI  - Dianion aggregates derived from lithiation of N-silyl allylamine.
AB  - [reaction: see text] Three different N-silyl-protected allylamines, i.e., N-TMS,
      N-TBDMS, and N-TIPS allylamine, were lihtiated by reaction with excess n
      butyllithium. Crystallization of the resulting dianions and X-ray structure
      determination yields three uniquely different aggregates.

PMID- 10964358
TI  - An expedient route to the Calabar bean alkaloids (-)-physovenine and (-)
      physostigmine.
AB  - An expedient route to the Calabar bean alkaloids (-)-physovenine and (-)
      physostigmine has been devised using a chiral building block which was originally
      designed for diastereocontrolled construction of aldohexoses.

PMID- 10964359
TI  - Molecular interpenetration within the columnar structure of crystalline anilino
      beta-cyclodextrin.
AB  - A single crystal of mono(6-anilino-6-deoxy)-beta-cyclodextrin was prepared, and
      its crystal structure was determined by X-ray crystallographic analysis, which
      clearly revealed that the anilino groups are consecutively included
      intermolecularly into the adjacent cyclodextrin cavities in the crystal, thus
      giving rise to a consolidated column, located on a 2(1)-screw axis.

PMID- 10964360
TI  - The occurrence of the human glycoconjugate C(2)-alpha-D-mannosylpyranosyl-L
      tryptophan in marine ascidians.
AB  - [structure: see text] The C-glycoconjugate C(2)-alpha-D-mannosylpyranosyl-L
      tryptophan (1), a metabolite known to be generated in humans through a novel
      posttranslational process, has been isolated from marine ascidians Leptoclinides
      dubius and Pharyngodictyon cauliflos and its N(alpha)-methyl derivative (2) from
      Ritterella rete.

PMID- 10964361
TI  - New synthetic technology for efficient construction of alpha-hydroxy-beta-amino
      amides via the Passerini reaction.
AB  - [reaction: see text] The Passerini reaction of N-protected amino aldehydes,
      isonitriles, and TFA using pyridine-type bases proceeds under mild conditions and
      directly affords alpha-hydroxy-beta-amino amide derivatives in moderate to high
      yields. These adducts are readily hydrolyzed to alpha-hydroxy-beta-amino
      carboxylic acids. Application of these key intermediates to concise syntheses of
      P(1)-alpha-ketoamide protease inhibitors is illustrated.

PMID- 10964362
TI  - A highly chemoselective oxidation of alcohols to carbonyl products with
      iodosobenzene diacetate mediated by chromium(III)(salen) complexes: synthetic and
      mechanistic aspects.
AB  - [reaction: see text] The catalytic oxidation of the allylic alcohols 1d-n with
      iodosobenzene diacetate, mediated by the [Cr(III)(salen)]X complex, affords the
      respective enones in excellent chemoselectivity for Cl(-) as counterion [complex
      A(Cl)], while for the counterions TfO(-) [complex A(TfO)] and PF(6)(-) [complex
      A(PF(6)())] nearly equal amounts of enone and epoxide are observed. This
      counterion-dependent oxidation of allylic alcohols by Cr(III)(salen) complexes is
      rationalized in terms of Lewis acid catalysis by the complex A(Cl) and redox
      catalysis for A(TfO) and A(PF(6)()).

PMID- 10964363
TI  - Convenient preparation of O-linked polymer-bound N-substituted hydroxylamines,
      intermediates for synthesis of N-substituted hydroxamic acids.
AB  - [reaction: see text] An efficient procedure for preparation of O-linked polymer
      bound N-substituted hydroxylamines by reduction of resin-bound oximes with
      borane.pyridine complex in the presence of dichloroacetic acid is reported. Other
      reducing systems commonly used for imine or oxime reduction were ineffective,
      including borane.pyridine in the presence of acetic acid. Oximes derived from a
      variety of aromatic and aliphatic aldehydes and ketones were successfully
      reduced. The N-substituted products were acylated and cleaved from resin to
      afford N-substituted hydroxamic acids.

PMID- 10964364
TI  - Self-regeneration of stereocenters: a practical enantiospecific synthesis of LFA
      1 antagonist BIRT-377.
AB  - [reaction: see text] An efficient enantiospecific synthesis of the LFA-1
      antagonist BIRT-377 has been achieved in 43% overall yield in eight steps. The
      key transformations involve the stereospecific formation of the trans
      imidazolidinone 7, subsequent alkylation, and the efficient hydrolysis of
      disubstituted imidazolidinone 9. The process is practical, robust, and cost
      effective; it has been successfully implemented in the pilot plant to produce
      multikilogram quantities of the drug BIRT-377.

PMID- 10964365
TI  - Diastereoselective synthesis of 3,4-dimethoxy-7-morphinanone: a potential route
      to morphine.
AB  - [reaction: see text] Diastereoselective synthesis of racemic 3,4-dimethoxy-7
      morphinanone from racemic 2-(2,3-dimethoxyphenyl)cyclohexen-1-ol has been
      achieved. The relative structure has been determined by transformation of the
      product into the known 3, 4-dimethoxy-6-morphinanone. Resolution of the starting
      cyclohexenol has also been accomplished for use in a future enantiocontrolled
      synthesis of morphine.

PMID- 10964366
TI  - Versatile and efficient solid-phase syntheses of pyrazoles and isoxazoles.
AB  - [reaction: see text] Condensation of aromatic or aliphatic esters with resin
      supported acetyl carboxylic acids 2, followed by cyclization with hydrazines or
      hydroxylamine, activation of the linker, and cleavage using amines provides
      highly substituted, isomeric pyrazoles or isoxazoles 5. This general method gives
      products in excellent yields and purities in which the ratio of the two isomers
      can be easily controlled. A variation of this scheme generates 1,4,5- and 1,3, 4
      trisubstituted pyrazoles and related isoxazoles. Post-cleavage reduction with
      borane converts pyrazole amides to amines such as 11.

PMID- 10964367
TI  - Tether-controlled cycloadditions for the asymmetric synthesis of decalins:
      increased selectivity in acetonitrile solvent.
AB  - [reaction: see text] The beneficial influence of cis-isopropylidene acetal tether
      control groups, to facilitate the asymmetric synthesis of substituted decalins by
      intramolecular Diels-Alder reactions, is described. Compared to trans-acetonides,
      these cases proceed under milder conditions to afford the cis-fused adducts from
      an endo transition state. An unusual acetonitrile solvent effect exerts a
      dramatic influence on the diastereoselectivity. This strategy leads to the chiral
      nonracemic bicyclo[4.4.0]decane core of diverse natural products.

PMID- 10964368
TI  - Cs(2)CO(3)-promoted efficient carbonate and carbamate synthesis on solid phase.
AB  - [reaction: see text] Mild and efficient preparation of alkyl carbonates and
      carbamates on solid supports is described herein. Alcohols or amines were coupled
      with Merrifield's resin through a CO(2) linker in the presence of cesium
      carbonate and tetrabutylammonium iodide (TBAI).

PMID- 10964369
TI  - Enantio- and diastereodifferentiating cis,trans-photoisomerization of 2beta,3beta
      diphenylcyclopropane-1alpha-carboxylic acid derivatives in organized media.
AB  - [reaction: see text] Four methods of asymmetric induction in the cis, trans
      photoisomerization of 2beta, 3beta-diphenylcyclopropane-1alpha-carboxylic acid
      derivatives were studied. Best results (ca. 80% de) were obtained by irradiation
      of chiral esters, amides, and salts in NaY and LiY zeolites and in the pure
      crystalline state.

PMID- 10964370
TI  - Absolute stereochemistry of amphidinolides G and H.
AB  - [structure: see text] Absolute stereochemistry of amphidinolides G (1) and H (2),
      potent cytotoxic 27- and 26-membered macrolides, respectively, isolated from a
      marine dinoflagellate Amphidinium sp., was determined by X-ray diffraction
      analysis, synthesis of a degradation product (3) of 2, and interconversion
      between 1 and 2.

PMID- 10964371
TI  - New protecting groups for 1,2-diols (boc- and moc-ethylidene). Cleavage of
      acetals with bases.
AB  - [reaction: see text] 1,2-Diols react at rt with alkyl propynoates, in the
      presence of 4-dimethylaminopyridine, to give cyclic acetals which are quite
      stable to acid-catalyzed hydrolysis or methanolysis. 1,3-Diols and 1, 4-diols do
      not form acetals with alkyl propynoates under the same conditions. Deprotection
      is accomplished with bases (via elimination and addition/elimination steps).

PMID- 10964372
TI  - Equilibrium constants between boron trifluoride etherate and carbonyl compounds
      in chloroform solution.
AB  - [reaction: see text] Equilibrium constants for boron trifluoride complexation
      with carbonyl compounds relative to diethyl ether were determined in CDCl(3).
      With benzaldehyde the equilibrium constant is 0.208. There is a 1.28-fold
      preference for BF(3) bonding to benzaldehyde-D over benzaldehyde-H. The rho(+)
      value for complexation with substituted benzaldehydes is -2.0. Equilibrium
      constants with cyclohexanone and isobutyraldehyde were found to be not very
      different from those predicted from the heats of addition of BF(3) relative to
      that for diethyl ether. The heats of addition can be correlated with Taft's beta
      values and with beta' values.

PMID- 10964373
TI  - Synthesis, resolution, and applications of 2, 2'-bis(diphenylphosphino)-3,3'-
      binaphtho[2,1-b]furan.
AB  - [structure: see text] A short five-step synthesis of (+/-)-2,2'
      bis(diphenylphosphino)-3, 3'-binaphtho[2,1-b]furan (BINAPFu, 1) starting from 2
      naphthoxyacetic acid is reported. The resolution of BINAPFu 1 was possible using
      our newly developed resolution procedure for phosphines wherein (1S)
      camphorsulfonyl azide was used to prepare the bisphosphinimine of BINAPFu via the
      Staundinger reaction. BINAPFu consistently outperformed BINAP in an asymmetric
      Heck reaction between 2,3-dihydrofuran and phenyl triflate.

PMID- 10964374
TI  - Practical modifications and applications of the sharpless asymmetric
      aminohydroxylation in the one-pot preparation of chiral oxazolidin-2-ones.
AB  - [reaction: see text] Chiral oxazolidin-2-ones are synthetically valuable as
      chiral auxiliaries, and many have pharmaceutically interesting biological
      activity. This communication focuses on a convenient, practical one-pot
      preparation of chiral 4,5-disubstituted oxazolidan-2-ones in good yield with high
      enantioselectivities, using a modified Sharpless asymmetric aminohydroxylation of
      beta-substituted styrene derivatives followed by base-mediated ring closure. This
      procedure has been demonstrated on both small and large scale, utilizing 1, 3
      dichloro-5,5-dimethyl hydantoin as an easily handled, commercially available
      substitute for tert-butyl hypochlorite.

PMID- 10964375
TI  - Cyanuryl-PNA monomer: synthesis and crystal structure.
AB  - [structure: see text] The chemical synthesis and crystal structure of the peptide
      nucleic acid (PNA) monomer 11 having cyanuric acid as the nucleobase is reported.
      The crystal structure of 11 shows molecular tapes arising from continuous
      intermolecular dimeric hydrogen bonding, with successive tapes held by single
      hydrogen bonds in the backbone.

PMID- 10964376
TI  - Clathration-induced asymmetric transformation of cefadroxil.
AB  - [structure: see text] The cephalosporin antibiotic Cefadroxil can be epimerized
      at the alpha-carbon of its amino acid side chain using pyridoxal as the mediator.
      By clathration with 2,7-dihydroxynaphthalene, the desired diastereomer can be
      selectively withdrawn from the equilibrating mixture of epimers. In this way, an
      asymmetric transformation of Cefadroxil can be accomplished. This opens the
      possibility of the production of Cefadroxil starting from racemic p
      hydroxyphenylglycine, in contrast to the current industrial synthesis that
      employs the D-amino acid in enantiopure form.

PMID- 10964377
TI  - Regioselective synthesis of 1,3,5-triaryl-4-alkylpyrazoles: novel ligands for the
      estrogen receptor.
AB  - [reaction: see structure] A regioselective synthesis of 4-alkyl-1,3,5
      triarylpyrazoles has been developed for the preparation of unsymmetrically
      substituted systems of interest as ligands for the estrogen receptor.

PMID- 10964378
TI  - Preparation and characterization of cholic acid-derived antimicrobial agents with
      controlled stabilities.
AB  - [reaction: see text] Novel cholic acid-derived antimicrobial agents that
      decompose under mildly basic conditions have been prepared. These compounds range
      in biological properties from potent antibacterial activity to effective
      permeabilization of the outer membranes of Gram-negative bacteria.

PMID- 10964379
TI  - On the antioxidant mechanism of curcumin: classical methods are needed to
      determine antioxidant mechanism and activity.
AB  - [reaction: see structure] The antioxidant activity of curcumin (1, 7-bis(4
      hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) was determined by inhibition
      of controlled initiation of styrene oxidation. Synthetic nonphenolic curcuminoids
      exhibited no antioxidant activity; therefore, curcumin is a classical phenolic
      chain-breaking antioxidant, donating H atoms from the phenolic groups not the
      CH(2) group as has been suggested (Jovanovic et al. J. Am. Chem. Soc. 1999, 121,
      9677). The antioxidant activities of o-methoxyphenols are decreased in hydrogen
      bond accepting media.

PMID- 10964380
TI  - Sparteine-mediated asymmetric nucleophilic substitution at prochiral, sp(3)
      hybridized carbon.
AB  - [reaction: see text] ++-Phenyl-1,3-dioxolanes (1) react with organolithium
      reagents (2), associated with (-)-sparteine, in the presence of BF(3).OEt(2) to
      afford chiral monosubstitution products 3. Enantioselectivity is highest if both
      1 and 2 carry alkyl substituents in the ortho position. However, the
      enantioselectivity decreases in the case of very bulky substituents such as tert
      butyl or phenyl.

PMID- 10964381
TI  - New allene synthesis via carbocupration-zinc carbenoid homologation and beta
      elimination sequence.
AB  - [reaction: see text] Polysubstituted propadienes are obtained in good to
      excellent yields by the consecutive carbocupration-homologation-beta-elimination
      reactions on the easily accessible alkynyl sulfoxides or sulfones. This one-pot
      reaction also allows the preparation of functionalized allenes.

PMID- 10964382
TI  - Functionalized hyperbranched polyethylene powder supports.
AB  - [reaction: see text] Polyethylene powders with useful loadings of functional
      groups are accessible by hyperbranched grafting chemistry. Using a 200 microm
      diameter high-density powder, loadings of up to 0.4 mmol/g of CO(2)H groups are
      attained. The carboxylic acid groups in the resulting powders can be further
      functionalized covalently or ionically and resulting powders have the physical
      durability and solvent resistance associated with polyethylene itself.

PMID- 10964383
TI  - Synthesis of 1,3-diynes via palladium-catalyzed reaction of 1, 1-dibromo-1
      alkenes.
AB  - [reaction: see text] Both symmetric and unsymmetric 1,3-diynes were prepared from
      the palladium-catalyzed reaction of 1,1-dibromo-1-alkenes. The formation of
      symmetric 1,3-diynes 2 (homocoupling) was catalyzed by a weak ligand, tris(2
      furyl)phosphine (TFP), and the addition of catalytic amount of CuI accelerated
      the reaction. The synthesis of unsymmetric 1,3-diynes 4 (the Sonogashira
      reaction) required a highly electron rich tris(4-methoxyphenyl)phosphine as the
      ligand, and CuI promotes the formation of byproduct 1,1-diynyl-1-alkenes 5.

PMID- 10964384
TI  - Electrophilic activation of hydrogen peroxide: selective oxidation reactions in
      perfluorinated alcohol solvents.
AB  - [reaction; see text] The catalytic electrophilic activation of hydrogen peroxide
      with transition metal compounds toward reaction with nucleophiles is a matter of
      very significant research and practical interest. We have now found that use of
      perfluorinated alcoholic solvents such as 1,1, 1,3,3,3-hexafluoro-2-propanol in
      the absence of catalysts allowed electrophilic activation of hydrogen peroxide
      toward epoxidation of alkenes and the Baeyer-Villiger oxidation of ketones.

PMID- 10964385
TI  - Novel fluorescence probes based on 2,6-donor-acceptor-substituted anthracene
      derivatives.
AB  - [reaction: see text] The fluorescence properties of selected derivatives of 6
      methoxyanthracene-2-carboxylic acid were studied. The corresponding ester and
      oxazoline derivatives exhibit a moderate solvatochromism, which is caused by the
      donor-acceptor interplay. The fluorescence band shift and intensity of oxazoline
      1f may be reversibly modulated by protonation or complexation with silver ions;
      thus, the oxazoline heterocycle serves as a useful substituent with switchable
      acceptor strength.

PMID- 10964386
TI  - The first regioselective alpha-deprotonation and functionalization of
      allenamides. An application in intramolecular Pauson-Khand-type cycloadditions.
AB  - [rection: see text] The first regioselective alpha-deprotonation and
      functionalization of electron-deficient allenamines are described here. The
      acidities of alpha- and gamma-allenic protons of these allenamides are readily
      differentiated using strong bases, thereby allowing regioselective substitutions
      at either the alpha- or gamma-allenic position. A specific synthetic application
      of the novel alpha-substituted allenamides in intramolecular Pauson-Khand-type
      cycloadditions is also described here.

PMID- 10964387
TI  - Inter- and intramolecular reductive coupling reactions: an approach to the
      phorbol skeleton.
AB  - [reaction: see text] An expeditious convergent route to the ABC-tricyclic core of
      the phorbol esters is described. The chemistry capitalizes upon both inter- and
      intramolecular reductive coupling processes promoted electrochemically and via
      the use of samarium diiodide.

PMID- 10964388
TI  - Unexpected reactivity of Imidazo[2,1-b]thiazolines with organometallic reagents.
AB  - [reaction: see text] The reaction of imidazo[2,1-b]thiazolines with various
      organometallic reagents is described. Nucleophilic attack of organolithium
      reagents on sulfur occurs with extrusion of ethylene to produce 2-thioalkyl- or 2
      thioarylimidazoles. The outcome with Grignard reagents, however, is less
      predictable, with some reagents adding at sulfur and others reacting at C-2 or
      not at all.

PMID- 10964389
TI  - Sulfur-containing palladacycles: efficient phosphine-free catalyst precursors for
      the Suzuki cross-coupling reaction at room temperature.
AB  - [reaction: see text] Cyclopalladated compounds derived from the ortho-metalation
      of benzylic tert-butyl thioethers are excellent catalyst precursors for the
      Suzuki cross-coupling reaction of aryl bromides and chlorides with phenylboronic
      acid under mild reaction conditions. A broad range of substrates and functional
      groups are tolerated in this protocol, and highly catalytic activity is attained.

PMID- 10964390
TI  - Synthesis of new bicyclic P-N ligands and their application in asymmetric Pd
      catalyzed pi-allyl alkylation and Heck reaction.
AB  - [structure: see text] The synthesis of phosphine oxazoline ligands based on P
      chiral 1-phosphanorbornadienes is reported. The use of these ligands in palladium
      catalyzed asymmetric allylation and Heck reaction is described.

PMID- 10964392
TI  - Efficient one-step conversion of primary aliphatic amines into primary alcohols:
      application to a model study for the total synthesis of (+/-)-scopadulin.
AB  - [reaction: see text] Treatment of primary aliphatic amines with KOH in diethylene
      glycol at 210 degrees C gives primary alcohols directly in good yields. A
      synthetic application to a model study of (+/-)-scopadulin is also described.

PMID- 10964391
TI  - Stereoselective reduction of alpha-bromopenicillanates by tributylphosphine.
AB  - [reaction: see text] Diastereoselective reduction of 6-bromo-6-substituted
      penicillanate esters has been achieved by treatment with tributylphosphine to
      give 6-substituted penicillanate esters. This reaction would appear to proceed
      through a phosphonium beta-lactam enolate species, followed by a
      diastereoselective protonation. This method has the advantage of being simple to
      carry out and it is mild, gives high diastereoselectivity, and should tolerate a
      number of functional groups in the substrates. Implications of these observations
      are discussed.

PMID- 10964393
TI  - Progress toward the total synthesis of bafilomycin A(1): stereoselective
      synthesis of the C15-C25 subunit by additions of nonracemic allenylzinc reagents
      to aldehydes.
AB  - [reaction: see text] A highly stereoselective synthesis of the C15-C25 subunit
      (2) of bafilomycin A(1) (1) has been accomplished by a route utilizing additions
      of chiral nonracemic allenylzinc reagents to aldehydes.

PMID- 10964394
TI  - Enantiospecific synthesis of N-Boc-Adda: a linear approach.
AB  - [structure: see text] Synthesis of the unusual amino acid (2S,3S,8S, 9S)-3-amino
      9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda), a unit of
      numerous cyanobacterial toxins, is described. Construction of the target molecule
      was achieved in 13 steps with an overall yield of 40%. The work is highlighted by
      a novel one-pot transformation from isoxazolidin-5-one intermediate 6 to the
      final product, a step that can also be used to form beta-amino acids.

PMID- 10964395
TI  - Stereoconvergent palladium-catalyzed carbonylation of both E and Z isomers of a 2
      trifloxy-1,3-butadiene.
AB  - [reaction: see text] Carbonylation of the illustrated Z-tetrasubstituted enol
      triflate followed by tandem silyloxy-Cope rearrangement leads to the CP-263, 114
      core ring system with the all-carbon quaternary stereocenter intact in 46% yield.
      Subjection of the corresponding E isomer to the same conditions gives the same
      product in 56% yield. This observation is explained by a mechanism involving
      isomerization of a pi-allyl palladium species involving an allenic intermediate.

PMID- 10964396
TI  - Highly functionalized Bicyclo[2.2.2]octenone-fused [60]fullerenes from masked o
      benzoquinones and C(60).
AB  - [reaction: see text] The Diels-Alder reactions of masked o-benzoquinones (MOBs)
      with [60]fullerene, affording novel and highly functionalized bicyclo[2.2.
      2]octenone-fused [60]fullerene derivatives, are described.

PMID- 10964397
TI  - Intramolecular 4 + 3 cycloadditions. Aspects of stereocontrol in the synthesis of
      cyclooctanoids. A synthesis of (+)-dactylol.
AB  - [reaction: see text] The judicious placement of stereocenters on precursors for 4
      + 3 cycloaddition reactions can lead to high levels of stereocontrol in the 4 + 3
      cycloaddition process of cyclopentenyl cations and tethered butadienes. This
      concept was successfully tested in the context of a synthesis of (+)-dactylol.

PMID- 10964398
TI  - Synthesis of oxepanes and trans-fused bisoxepanes via biomimetic, endo
      regioselective tandem oxacyclizations of polyepoxides.
AB  - [reaction: see text] This communication describes the first examples of tandem
      endo-regioselective and stereospecific oxacyclizations of 1, 5-diepoxides to
      oxepane products and a similar tandem oxacyclization of 1,5,9-triepoxides to
      fused bisoxepane cyclic carbonates. A mechanism for these biomimetic
      oxacyclizations is proposed in which the epoxides act as both electrophilic and
      nucleophilic reaction partners.

PMID- 10964399
TI  - A dilution immunoassay to measure myosin regulatory light chain phosphorylation.
AB  - We examined the quantitation of myosin regulatory light chain phosphorylation
      (MRLCP) by Western blot and found both offset and saturation errors. The
      desirable characteristics of an MRLCP assay are that the dynamic range be 60- to
      100-fold and that the detection threshold be known and preferably very small
      relative to total MRLC concentration. No technique examined provided all these
      characteristics. However, accurate measurements can be obtained by including
      serial dilutions of the sample to provide a fractional calibration scale in terms
      of the dephosphorylated light chain and by using interpolation of the
      phosphorylated band signal intensity to provide values for the relative
      phosphorylation ratio. We found that this method offers several advantages over
      methods that rely on signal ratios from single samples: The dilution ratio method
      is less subject to errors from differences in protein load, it offers estimates
      of the error in the individual measurement, and has some redundancy that
      increases the likelihood of obtaining a valid measurement despite gel or membrane
      artifacts.

PMID- 10964400
TI  - A homogeneous method to measure aminoacyl-tRNA synthetase aminoacylation activity
      using scintillation proximity assay technology.
AB  - A new method to measure the aminoacylation of tRNA based upon the use of the
      scintillation proximity assay (SPA) technology has been developed. The assay
      detects incorporation of radiolabeled amino acids into cognate tRNA, catalyzed by
      a specific aminoacyl-tRNA synthetase (aaRS). Under acidic conditions, uncoated
      yttrium silicate SPA beads were found to bind tRNA aggregates, while the
      radiolabeled amino acid substrate remains in solution, resulting in good signal
      discrimination of these two species in the absence of any separation steps. The
      usefulness of this approach was demonstrated by measurement of steady-state
      kinetic constants and inhibitor binding constants for a range of aaRS enzymes in
      comparison with data from standard, trichloroacetic acid-precipitation-based
      assays. In all cases, the data were quantitatively comparable. Although the
      radioisotopic counting efficiency of the SPA method was less than that of
      standard liquid scintillation counting, the statistical performance (i.e., signal
      to background, variability, stability) of the SPA assays was at least equivalent
      to the separation-based methods. The assay was also shown to work well in
      miniaturized 384-well microtiter plate formats, resulting in considerable reagent
      savings. In summary, a new method to characterize aaRS activity is described that
      is faster and more amenable to high-throughput screening than traditional
      methods.

PMID- 10964401
TI  - Heterogeneity in human cardiac troponin I standards.
AB  - The LC-MS analysis of recombinant cardiac troponin I (cTnI) and cTnI extracted
      from human hearts showed a high degree of structural heterogeneity among all
      samples. The examined recombinant cTnI samples indicated posttranslational
      modifications, presumably due to their purification (i.e., 2-mercaptoethanol
      adducts and carbamylation) and related to their expression (i.e., an N-terminal
      expression tag). The extracted cTnI samples, while having a higher degree of
      structural heterogeneity, showed less structural variance between samples than
      the recombinant proteins. The LC-MS analysis of the extracted cTnI samples
      provided evidence of posttranslational modification by phosphorylation,
      acetylation, proteolytic cleavage, and intrachain disulfide bond formation.

PMID- 10964402
TI  - Single-step gas chromatography-mass spectrometry analysis of glycolipid
      constituents as heptafluorobutyrate derivatives with a special reference to the
      lipid portion.
AB  - In a previous work (Zanetta et al. Glycobiology 9, 255-266 (1999)), it was
      reported that all constituents of gangliosides could be obtained as
      heptafluorobutyrate derivatives after methanolysis in a single gas chromatography
      analysis. This report demonstrates that gas chromatography coupled with mass
      spectrometry in the electron impact mode allows identification and quantification
      of long-chain bases and fatty acids without interference from monosaccharides. On
      the basis of ions specific for families and for individual compounds,
      sphingosines, sphinganines, and phytosphingosines (including ramified,
      unsaturated, hydroxylated, and etherified compounds) can be identified. Fatty
      acid methyl esters, including linear, ramified, unsaturated, and hydroxylated
      species, are identified and quantified in the same way. Possible extensions of
      this method to the fatty moiety of other lipids (alkylacylglycerol and dimethyl
      acetal) are discussed.

PMID- 10964403
TI  - A critical evaluation of the effect of sorbitol on the ferric-xylenol orange
      hydroperoxide assay.
AB  - Measurement of hydroperoxide concentration by the ferric-xylenol orange assay has
      the advantages of simplicity, convenience, and inertness to oxygen (Gay, C., et
      al. (1999) Anal. Biochem. 273, 149-155). However, its sensitivity is limited by
      the molar absorption coefficients, which are less than 50,000 M(-1) cm(-1) for
      most hydroperoxides. An earlier report showed that this could be significantly
      enhanced by the inclusion of 100 mM sorbitol in the assay solution, resulting in
      an increase of the apparent absorption coefficient for H(2)O(2) from 4.46 x 10(4)
      to 2.24 x 10(5) M(-1) cm(-1) (Wolff, S. P. (1994) Methods Enzymol. 233, 182-189).
      It was claimed that the technique was also valid for other hydroperoxides, such
      as butyl and cumyl. In an attempt to extend this modification to a wider range of
      hydroperoxides, we have confirmed the enhancement of the assay of H2O2 by
      sorbitol. However, the sensitivity of the measurements of butyl, cumyl, amino
      acid, protein, and human blood serum hydroperoxides was only approximately
      doubled by the inclusion of sorbitol. A mechanism explaining the difference in
      the assay of H2O2 and the organic hydroperoxides is proposed.

PMID- 10964404
TI  - Quantitative measurement of bitagged recombinant proteins using an immunometric
      assay: application to an anti-substance P recombinant antibody.
AB  - We have developed two different immunometric assays to directly quantify both the
      total and the active fractions of a recombinant antibody (single chain fragment
      variable, or ScFv) as obtained in a crude extract from an Escherichia coli
      expression system. For total determination, the assay is based on the
      simultaneous recognition of two different peptide Tag sequences (Ha-Tag and Myc
      Tag) at each of the N- and C-terminal extremities of the recombinant protein. A
      monoclonal antibody (mAb 12CA5, directed against Ha-Tag), coated on microtiter
      plates, is used for capture, and the mAb 9E10 (directed against Myc-Tag), labeled
      with acetylcholinesterase (AChE, EC 3.1.1.7), acts as tracer. In parallel, for
      the determination of the active fraction, the capture is performed using
      microtiter plates coated with the antigen, while solid-phase-immobilized ScFv is
      measured using the same 9E10 tracer mAb. A synthetic peptide in which the two Tag
      sequences were joined was used as a standard, thus avoiding the laborious
      purification of a recombinant protein as reference. The method was applied to the
      direct measurement, in periplasmic extracts, of the total and active fractions of
      an ScFv produced at different induction temperatures.

PMID- 10964405
TI  - A method for the large-scale cloning of nuclear proteins and nuclear targeting
      sequences on a functional basis.
AB  - We describe here a selection strategy allowing the cloning of sequences that
      contain a functional nuclear targeting signal. Our method relies on the use of
      green fluorescent protein fusion proteins to identify nuclear targeting
      sequences. Transfected cells expressing nuclear protein fusions were isolated on
      the basis of their nuclear fluorescence using flow cytometry and the transfected
      DNAs were recovered after bacterial transformation with total DNA from pools of
      sorted cells. Starting from a cDNA expression library, in which only 1% of the
      expressed proteins were nuclear, we obtained a 70-fold enrichment in nuclear
      protein-encoding clones after a single round of selection. Among the 63 clones
      that have been partially sequenced to date, 25 (40%) corresponded to known
      nuclear proteins and 13 (20%) to previously uncharacterized sequences. Despite
      their ability to target the green fluorescent protein marker to the cell nucleus,
      about half of the cloned sequences did not encode canonical basic or bipartite
      nuclear localization signals. The method can thus be applied to the large-scale
      cloning of functional nuclear targeting sequences, which opens the way to a wide
      investigation of nuclear import mechanisms and to the identification of
      previously unknown nuclear proteins.

PMID- 10964406
TI  - Deacylation kinetics analysis of Streptococcus pneumoniae penicillin-binding
      protein 2x mutants resistant to beta-lactam antibiotics using electrospray
      ionization- mass spectrometry.
AB  - Penicillin-binding proteins (PBPs) catalyze the transpeptidase reaction involved
      in peptidoglycan synthesis and are covalently inhibited by the beta-lactam
      antibiotics. In a previous work we have focused on acylation efficiency
      measurements of various Streptococcus pneumoniae PBP2x* mutants to study the
      molecular determinants of resistance to beta-lactams. In the present paper we
      have developed a method to improve an accurate determination of the deacylation
      rate constant using electrospray ionization-mass spectrometry. This method is
      adaptable to the analysis of deacylation of any beta-lactam. Compared to the
      fluorographic technique, the ESI-MS method is insensitive to variations in the
      concentration of functional proteins and is therefore more reliable. We have
      established that the resistance of PBPs to beta-lactams is mostly due to a
      decrease of the acylation efficiency with only marginal effects on the
      deacylation rates.

PMID- 10964407
TI  - Application of native-state electrospray mass spectrometry to identify zinc
      binding sites on engineered hemoglobin.
AB  - We report the utility of native-state mass spectrometry to detect zinc ion
      binding to the engineered hemoglobin rHb52. Various preparations of this
      recombinant hemoglobin had significantly different oxygen affinities. Detailed
      characterization of denatured globins did not show any difference between
      analyzed hemoglobin molecules. However, when solutions of intact hemoglobin
      pseudotetramers were analyzed by native-state electrospray mass spectrometry, a
      significant shift in the mass spectrum was observed, indicating labile
      modification of hemoglobin. Using collision-induced dissociation (CID), we found
      a mass gain of 63 Da located on the beta-globin. EDTA treatment of modified
      hemoglobin prior to the infusion removed the modification and restored the
      predicted oxygen affinity. Ion-trap fragmentation of the +8 charged ion of
      modified beta-globin showed a neutral loss of 96+/-1 Da, consistent with neutral
      loss of zinc sulfide. These findings indicated zinc binding to the beta-globin
      through a cysteine residue. Involvement of Cys93 was confirmed by kinetics of
      cysteine residue reactivity with dithiodipyridine and peptide mapping. Presence
      of zinc was confirmed by ICP-MS metal analysis.

PMID- 10964408
TI  - Offline coupling of low-pressure anion-exchange chromatography with MALDI-MS to
      determine the elution order of human milk oligosaccharides.
AB  - Pooled human milk oligosaccharides were separated into neutral and several acidic
      oligosaccharide fractions by preparative anion-exchange chromatography (AEC)
      using AG 1-X2. The oligosaccharides were eluted stepwise using deionized water
      and three different concentrations of ammonium acetate buffer, pH 6.8. The
      elution order of the compounds was determined directly by matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) analysis of the AEC effluent
      without any cleanup or concentration steps. Up to a concentration of 500 mM
      ammonium acetate, the masses of acidic oligosaccharides could be detected by
      screening the fractions in an automated mode. The combination of the improved
      chromatographic procedure, the applied MALDI matrices, and operating parameters
      is suitable for the detection of neutral oligosaccharides as well as acidic
      oligosaccharides. The method provides high sensitivity and mass accuracy,
      including for the high-molecular-weight monosialylated oligosaccharides up to
      2751.5 Da. The applied ionic strength of the anion-exchange eluents enables a
      rapid and an unambiguous composition assignment by MALDI-MS for neutral,
      monosialylated, and disialylated oligosaccharides from human milk. The acidic
      fractions have to be desalted by electrodialysis and were finally analyzed by
      HPAEC-PAD to get a high-resolution "fingerprint" of structures present in each
      fraction. From these analyses, it can be concluded that the isomeric variety of
      monosialylated oligosaccharides occurring in human milk is higher than estimated
      before.

PMID- 10964409
TI  - A method for global analysis of complex proteomes using sample prefractionation
      by solution isoelectrofocusing prior to two-dimensional electrophoresis.
AB  - Two-dimensional electrophoresis is a critical technique for proteome research,
      but currently available methods are not capable of resolving the >10,000 protein
      components in most eukaryotic proteomes. We have developed and demonstrated the
      utility of a novel solution isoelectrofocusing device and method that can
      reproducibly prefractionate cell extracts into well-defined pools prior to 2D
      PAGE on a scale directly compatible with the high sensitivity of proteome
      studies. A prototype device was used to separate metabolically radiolabeled
      Escherichia coli extracts in method optimization and proof-of-principle
      experiments. Samples were loaded into separation chambers divided by thin
      polyacrylamide gels containing immobilines at specific pH values and
      isoelectrically focused for several hours, which resulted in well-resolved
      fractions. Total recoveries in the fractionated samples were greater than 80% and
      most protein spots in the original sample were recovered after this
      prefractionation step. Nonideal behavior (precipitation/aggregation), typically
      encountered when unfractionated samples at high protein loads were applied
      directly to either narrow- or broad-range IPG gels, was dramatically reduced.
      Hence this approach allows increases in overall protein loads, resolution, and
      dynamic detection range compared with either alternative prefractionation methods
      or direct use of parallel narrow pH range gels without sample prefractionation.
      The pH ranges and number of fractions can be readily adapted to the requirements
      of specific types of samples and projects. This method should allow quantitative
      comparisons of at least 10,000 protein components on a series of narrow pH range
      gels, and protein detection limits are estimated to be 1000 molecules per cell
      when mammalian proteomes are fractionated into five or more pools.

PMID- 10964410
TI  - Structural elucidation of zwitterionic sugar cores from glycosphingolipids by
      nanoelectrospray ionization-ion-trap mass spectrometry.
AB  - The use of electrospray ionization (ESI)-ion-trap mass spectrometry (ITMS) for
      analysis of zwitterionic, glycolipid-derived sugar cores of glycosphingolipids is
      described. The capability of the method to perform multiple steps of
      fragmentation (MS(n)) allows structural characterization of these compounds. No
      derivatization of the released oligosaccharides is necessary when using nano-ESI
      with sample solution flow rates of about 30 nL/min. Investigations of positive as
      well as negative ions in fragmentation experiments up to MS(4) permit
      determination of the sequence of sugar units, their linkage positions, and the
      exact location of the substituents phosphocholine and phosphoethanolamine. In the
      case of phosphocholine, chemical cleavage of this substituent was necessary to
      obtain all the linkage information. Approximately 150-250 ng of sample was needed
      for each analysis.

PMID- 10964411
TI  - Recovery of sodium dodecyl sulfate-proteins from gel electrophoretic bands in a
      single electroelution step for mass spectrometric analysis.
AB  - Mass spectrometric analysis of proteins derived from bands in gel electrophoresis
      is incompatible with the covalent fluorescent labeling of the protein. Thus, if
      one wishes to take advantage of the capacity for computer-directed electroelution
      of electrophoresis apparatus with intermittent fluorescent scanning of the
      migration path, the protein must be labeled fluorescently in a noncovalent,
      reversible fashion. This was recently achieved by staining of SDS-proteins with
      Cascade blue and electrophoresis in barbital buffer. However, the method was not
      a practical one for the purpose of isolating proteins from gel electrophoretic
      bands and their transfer into the mass spectrometer for three reasons: (i) Ten
      consecutive electroelution steps were required to obviate pH changes in the
      electroelution chamber; (ii) electroeluates from six gel electrophoretic lanes
      needed to be pooled; (iii) excessive protein loads ranging from 7 to 33
      microg/pool were required. The present study reports the solution to those three
      problems. Mass spectrometric (MALDI-TOF) characterization of five proteins was
      demonstrated (i) after a single electroelution step; (ii) using electroelution
      from a single gel of 0.3-cm(2) cross-sectional area; and (iii) using a protein
      load of 2 (in one case 4) microg. However, the migration rates of the Cascade
      blue-SDS-protein-barbital complexes derived from proteins with widely varying
      molecular weights proved to be the same. Thus, despite the three advances made,
      the method to date remains restricted to samples of single proteins.

PMID- 10964412
TI  - High-performance liquid chromatography with coulometric electrode array detector
      for the determination of quercetin levels in cells of the immune system.
AB  - There is mounting evidence emphasizing the importance of intracellular
      antioxidant levels for maintenance of the immune function. The flavonoid
      quercetin, a natural antioxidant, has been shown to modulate enzymes involved in
      the regulation of the inflammatory response. However, up to now, there have been
      no studies describing quercetin levels in cells of the immune system. A gradient
      reversed-phase HPLC technique to identify and quantify intracellular levels of
      quercetin and its application in mice splenocytes are described. Mobile phases
      were a 0.01 M sodium phosphate monobasic solution adjusted to pH 2.8 with 85%
      orthophosphoric acid (buffer, Solvent A) and methanol (Solvent B) with a flow
      rate of 1 ml/min. An eight-channel coulometric electrode array detector was used.
      In vitro supplementation with increasing concentration of quercetin (25, 50, and
      100 microM) raises intracellular quercetin levels in a dose-dependent manner. The
      method has the required features of specificity and sensitivity for monitoring
      quercetin uptake in cells of the immune system.

PMID- 10964414
TI  - Colorimetric and fluorimetric assays to quantitate micromolar concentrations of
      transition metals.
AB  - Transition metal ions, although maintained at low concentrations, play diverse
      important roles in many biological processes. Two assays useful for the rapid
      quantification of a range of first-row transition metal ions have been developed.
      The colorimetric assay extends the 4-(2-pyridylazo)resorcinol assay of Hunt et
      al. (J. Biol. Chem. 255, 14793 (1984)) to measure nanomole quantities of Co(2+),
      Ni(2+), and Cu(2+) as well as Zn(2+). The fluorimetric assay takes advantage of
      the coordination of a number of metal ions (Mn(2+), Co(2+), Ni(2+), Cu(2+),
      Zn(2+), Cd(2+)) by Fura-2 and can also be used to measure nanomole quantities of
      these ions. The assays developed here have the advantage of not requiring the
      extensive sample preparation necessary for other methodologies, such as atomic
      absorption spectroscopy and inductively coupled plasma emission spectroscopy
      (ICPES), while being comparable in accuracy to the detection limits of ICPES for
      the first-row transition metal ions. To demonstrate the effectiveness of these
      assays, we determined the affinity of carbonic anhydrase II (CA II), a
      prototypical zinc enzyme, for Ni(2+) and Cd(2+). These data indicate that CA II
      binds transition metals with high affinity and is much more selective for Zn(2+)
      over Ni(2+) or Cd(2+) than most small-molecule chelators or other metalloenzymes.

PMID- 10964413
TI  - Determination of boronophenylalanine in biological samples using precolumn o
      phthalaldehyde derivatization and reversed-phase high-performance liquid
      chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method for the detection
      of boronophenylalanine is described. Determination was obtained by precolumn
      reaction of o-phthalaldehyde with a mixture of standard amino acids containing
      boronophenylalanine and separating the corresponding o-phthalaldehyde
      derivatives, using a Kromasil C-18, 250 x 4.6 mm, 5-microm particle size column,
      a step gradient with two buffers, a flow rate of 1.2 ml/min, a column temperature
      of 23 degrees C, and fluorimetric detection (excitation and emission wavelengths
      of 330 and 430 nm, respectively). The use of such a method for assaying
      boronophenylalanine in biological samples was tested in neutralized perchloric
      acid blood and cerebral tissue extracts of rats treated with intracarotid
      administration of 300 mg/kg of body weight boronophenylalanine. Results of these
      experiments showed that the present HPLC method represents a valid alternative to
      currently available analytical techniques for assaying boronophenylalanine based
      on boron determination in terms of reproducibility, recovery, or sensitivity.
      Therefore, it is suggested that the present method may routinely be used in all
      preclinical and clinical studies in which quantification of circulating and
      tissue concentrations of boronophenylalanine is critical for the application of
      boron neutron capture therapy.

PMID- 10964415
TI  - A reporter gene assay for high-throughput screening of G-protein-coupled
      receptors stably or transiently expressed in HEK293 EBNA cells grown in
      suspension culture.
AB  - We describe in detail a robust, sensitive, and versatile functional assay for G
      protein-coupled receptors (GPCRs) expressed in human embryonic kidney (HEK) 293
      EBNA (Epstein-Barr virus nuclear antigen) (designated 293E) cells. The ability to
      grow these cells in suspension, in conjunction with the use of the secreted form
      of the human placental alkaline phosphatase (SEAP) as the reporter enzyme
      transcriptionally regulated by 5-cyclic AMP (cAMP) response elements (CREs) (Chen
      et al., Anal. Biochem. 226, 349-354 (1995)), makes this CRE-SEAP assay
      potentially attractive for high-throughput screening (HTS). A 293E clonal cell
      line, stably transfected with the CRE-SEAP plasmid, was initially characterized
      with compounds known to activate intracellular signal transduction pathways
      similar to those activated by GPCRs. Forskolin and cAMP analogues were potent at
      inducing SEAP expression but calcium ionophores (A23187 and ionomycin) were
      without effect. The forskolin response was also potentiated by the protein kinase
      C activator phorbol myristate acetate as well as the phosphodiesterase inhibitor
      isobutylmethylxanthine. Previously established cell lines expressing the
      G(alphas)-coupled DP or the G(alphaq)-coupled-EP(1) prostanoid receptors were
      stably transfected with the reporter gene construct and clones were selected
      based on their ability to secrete SEAP upon agonist challenge. Pharmacological
      characterization of the DP and EP(1) receptors displayed a similar rank order of
      potency for several known prostanoids and related compounds to that previously
      reported using classical binding assays or other functional assays. The CRE-SEAP
      assay was also used to characterize the EP(1) receptor antagonists SC-51322, SC
      51089, and AH6809. In summary, we have established a reporter gene assay for
      GPCRs that couple to both G(alphas) and G(alphaq) and is amenable to HTS of both
      agonists and antagonists.

PMID- 10964416
TI  - Functionality of a membrane protein in bicelles.
AB  - Bicelles are bilayered discoidal lipid-detergent assemblies which are useful as
      model membranes. To date, there has been no direct demonstration of functional
      viability for an integral membrane protein reconstituted into bicelles. In this
      contribution, the catalytic activity of diacylglycerol kinase (DAGK) was measured
      following reconstitution into several different bicelle systems and compared to
      activities measured in traditional mixed micelles and vesicles. For the most
      optimal bicelle systems tested, DAGK activities approached those observed in
      mixed micelles or vesicles. For some other bicellar mixtures tested, activities
      were much lower, with steady-state kinetic data indicating reduced V(max) rather
      than perturbations in substrate K(m). Catalytically, DAGK showed a strong
      preference for bicelles containing 3-(cholamidopropyl)dimethylammonio-2-hydroxy-1
      propanesulfonate (CHAPSO) as the detergentcomponent relative to short-chained
      phosphatidylcholine.DAGK also exhibited a preference for
      dimyristoylphosphatidylcholine or dipalmitoylphosphatidylcholine bicelles
      relative to those of dilauroylphosphatidylcholine.

PMID- 10964417
TI  - Evaluation of the binding between potential anti-HIV DNA-based drugs and viral
      envelope glycoprotein gp120 by capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - The fusion of the human immunodeficiency virus (HIV) with the target cell was
      assisted by the interaction between the viral envelope glycoprotein HIV-1 gp120
      and a chemokine receptor. Studies have shown that the efficiency of the binding
      depends on the presence of the V3 loop of the gp120 which is known to interact
      with polyanions, such as phosphorothioate oligodeoxynucleotides (Sd, potential
      anti-HIV drugs). In this study, capillary electrophoresis with laser-induced
      fluorescence detection (CE-LIF) was used to systematically evaluate binding
      between Sd and HIV-1 gp120. A 25-mer fluorescently tagged phosphorothioate
      oligodeoxynucleotide (GEM) was employed as a probe to study this interaction. The
      dissociation constant (K(d)) between GEM and gp120 was determined to be 0.98 nM
      by Scatchard analysis. The competition constants (K(c)) of a set of Sd that
      compete with GEM for binding to gp120 were also determined. The results showed
      that the interaction had a strong dependence on the sulfur phosphorothioate
      backbone. Chain length and the sequence of Sd also affect the ability of binding
      to gp120. The ability to study the protein-drug binding in the solution with
      minimal sample consumption makes CE-LIF very attractive for biological studies.

PMID- 10964418
TI  - High-performance liquid chromatography determination of N- and O-demethylase
      activities of chemicals in human liver microsomes: application of postcolumn
      fluorescence derivatization using Nash reagent.
AB  - Formaldehyde is liberated in the process of cytochrome P450 (CYP) mediated
      demethylation of a wide variety of compounds containing the CH(3)N or CH(3)O
      functionality. A highly sensitive method using a high-performance liquid
      chromatography (HPLC) system with postcolumn derivatization was developed to
      measure the liberated formaldehyde as N- and O-demethylase activity of drugs in
      human liver microsomes. Following the chromatographic separation of formaldehyde
      on a C18 column, the formaldehyde was reacted with the Nash reagent in the
      postcolumn reactor at 100 degrees C and detected by the fluorescence method. The
      results showed that the present method has excellent precision and accuracy. The
      intra- and interassay variances of this method were less than 10%. The newly
      developed HPLC method was found to be about 80-fold more sensitive than the
      colorimetric method in detection of formaldehyde. The N-demethylase activity of
      sertraline in rat liver microsomes determined by the present method did not
      differ from those detected by previous methods quantifying produced desmethyl
      metabolite. The present method has been successfully applied to determine the N
      demethylase activities of several drugs, including aminopyrine, erythromycin,
      fluoxetine, S-mephenytoin, and sertraline, in human liver microsomes. This assay
      should be useful for generic analysis of N- and O-demethylase activities of
      xenobiotic and endobiotic chemicals by CYP enzymes.

PMID- 10964419
TI  - Determination of the refractive index increments of small molecules for
      correction of surface plasmon resonance data.
AB  - The refractive index increments (RIIs) of several important low-molecular-weight
      compounds that bind to DNA or RNA were determined with a differential
      refractometer for correction of data obtained on surface plasmon resonance (SPR)
      biosensors. Although the ability to investigate small molecule-macromolecule
      interactions by SPR is relatively new, the technique is rapidly becoming a
      primary method to screen focused combinatorial libraries and to quantitatively
      characterize the interactions between compounds identified as binders and target
      macromolecules. The most widely used SPR analysis software, BIAevaluation
      (Biacore, Inc.), assumes that the RIIs of ligand and macromolecule are identical.
      While the assumption is reasonable for studies involving like molecules such as
      protein-protein interactions, results presented here demonstrate that RII values
      for small molecules can be significantly different than those of protein or
      nucleic acid receptors. The results also show that the RII values can vary
      greatly depending on the structure of the small molecule. Indeed, the RIIs of the
      molecules investigated here differ by a factor of 2. Any difference in the RII of
      interacting molecules must be considered for complete analysis of SPR data.
      Failure to correct for RII differences can result in serious error in data
      interpretation, especially for systems involving a ligand:receptor stoichiometry
      greater than 1. The results serve as the beginning of an SPR correction database
      for the RIIs of small molecules. Additionally, the results can be used to
      approximate the RIIs of a variety of other small molecules.

PMID- 10964421
TI  - Use of high-resolution magic angle spinning nuclear magnetic resonance
      spectroscopy for in situ studies of low-molecular-mass compounds in red algae.
AB  - The use of high-resolution magic angle spinning NMR spectroscopy for in situ
      studies of low-molecular-mass compounds in red algae has been studied. The impact
      of different acquisition parameters on the resulting T(2)-filtered one
      dimensional high-resolution magic angle spinning (1)H NMR spectra is described.
      The technique was used for in situ identification and quantification of some low
      molecular-mass algal metabolites.

PMID- 10964420
TI  - A labeling, detection, and purification system based on 4-hydroxyazobenzene-2
      carboxylic acid: an extension of the avidin-biotin system.
AB  - We introduce a new nonradioactive, chromogenic label based on 4-hydroxyazobenzene
      2-carboxylic acid (HABA), which is suitable for bioanalytical application, e.g.,
      detection, localization, isolation, and purification. The HABA label is superior
      to other systems where it is difficult to separate labeled from unlabeled
      molecules or to determine the amount of label. HABA is readily detected
      spectroscopically by its absorption at 350 nm or by its interaction with avidin
      that results in a red shift to 500 nm. The HABA reagents described can be
      conjugated to a variety of functional groups on biomolecules and purified
      thereafter by affinity chromatography on an avidin column. The interaction of the
      HABAylated biomolecules with their corresponding targets is detected with high
      affinity anti-HABA antibodies or with avidin. The nonradioactive, chromogenic
      HABA-based reagents form a homogeneous system that can complement or replace
      systems where facile quantification of the label is desired.

PMID- 10964422
TI  - Evaluation of in vitro bone resorption: high-performance liquid chromatography
      measurement of the pyridinolines released in osteoclast cultures.
AB  - None of the currently used methods to evaluate bone resorption by osteoclasts
      cultured on bone substrate measures directly the amounts of degraded bone
      collagen, which is a direct reflection of the osteoclast "work done." We
      therefore propose a reliable biochemical method to evaluate the in vitro
      collagenolysis process. Bone-resorbing activity was evaluated, after HPLC
      separation, by fluorimetric measurement of hydroxylysylpyridinoline (HP), a
      collagen cross-link molecule, released in culture supernatants. We first confirm
      previous data reporting that HP is released in the culture medium in a peptide
      conjugated form. After acid hydrolysis, we show that HP is highly correlated with
      the lacunae area (r = 0.68, P<0.0001) and with the amounts of antigenic collagen
      fragments (Cross-laps for culture) released in culture medium (r = 0.77,
      P<0.0002). Using a cysteine protease inhibitor, we observed that lacunae areas
      are dramatically less inhibited (35% inhibition) than the release of bone
      degraded products, including HP and antigenic collagen fragments (96 and 92%
      inhibition, respectively). Coupled to the resorbed area measurement, biochemical
      evaluations offer both quantitative and qualitative complementary measurements of
      the osteoclastic bone-resorbing process.

PMID- 10964423
TI  - Implementation of a continuous, enzyme-coupled fluorescence assay for high
      throughput analysis of glutamate-producing enzymes.
AB  - Enzymatic formation of glutamate is critical to numerous biological pathways.
      However, current methods for assaying the activities of glutamate-forming enzymes
      are not particularly suitable for high-throughput screening in drug discovery. We
      present a continuous-read, fluorometric assay for high-throughput analysis of
      glutaminases. This assay is adapted to a microplate format and employs glutamate
      oxidase and horseradish peroxidase to couple glutamate formation to production of
      the fluorescent reporter molecule, resorufin, for enhancement of sensitivity (M.
      Zhou, Z. Diwu, N. Panchuk-Voloshina, and R. P. Haughland, 1997, Anal. Biochem.
      253, 162-168). Described herein is the selection of suitable levels of coupling
      enzymes for optimal kinetic response and lag time of the reporter system, based
      on the kinetic characteristics of the individual coupling enzymes. Finally,
      implementation of the assay in a format for high-throughput kinetic analysis of
      glutaminases is demonstrated for Escherichia coli carbamoyl phosphate synthase.
      Derived kinetic constants are comparable to literature values determined using a
      variety of assay techniques.

PMID- 10964424
TI  - Assay for lytic transglycosylases: a family of peptidoglycan lyases.
AB  - An assay has been developed to monitor the activity of the lytic
      transglycosylases which does not involve the use of radiolabel. Samples of lytic
      transglycosylase were incubated with isolated and purified insoluble
      peptidoglycan as substrate for varying lengths of time. Residual insoluble
      material was removed by ultracentrifugation in a microfuge and the solubilized
      components were treated with sodium borohydride prior to acid hydrolysis. The
      optimal conditions for this acid hydrolysis were established to be incubation at
      96 degrees C for 1 h in 6 M HCl, in vacuo. The hydrolyzed samples were subjected
      to amino acid/sugar analysis by cation-exchange chromatography on a Beckman
      System Gold amino acid analyzer. To effect a clear resolution of muramic acid
      from serine and glutamic acid, the equilibration buffer was modified to be
      composed of 33 mM sodium citrate, pH 3.12. The product of the lyase reaction of
      the lytic transglycosylases are 1,6-anhydromuramyl residues, which are not
      reduced by the sodium borohydride treatment. On the other hand, the muramyl
      residues arising at the reducing ends of peptidoglycan after treatment with
      muramidases (hydrolyases) are reduced to muramitol residues, which elute from the
      amino acid analyzer prior to aspartic acid. This assay thus distinguishes the
      activity of the two enzymes and was applied to determine the initial activities
      of increasing concentrations of a soluble derivative of lytic transglycosylase B
      from the opportunistic pathogen Pseudomonas aeruginosa.

PMID- 10964425
TI  - Use of bioluminometry for determination of active yeast biomass immobilized in
      ionotropic hydrogels.
AB  - The technique of bioluminometry was used to determine the biomass concentration
      of yeast cells immobilized in ionotropic hydrogel beads, including alginate,
      pectate, and kappa-carrageenan. The method uses determination of ATP extracted
      from viable cells, the concentration of which is then expressed as the active
      biomass concentration. Seven yeast strains divided into three categories
      (brewing, wine-making, and ethanol-producing yeasts) were tested, and different
      biomass concentrations were determined in all three immobilization materials. The
      described method is characterized by a good correlation (up to 99%) to classical
      dry biomass determination. The method is quicker, easier, and not so laborious,
      providing sufficient determination accuracy, and can be used for a rapid
      estimation of viable biomass in most biotechnological processes using immobilized
      living cells.

PMID- 10964426
TI  - Detection of beta-amyloid peptide aggregation using DNA electrophoresis.
AB  - DNA could readily associate with the aggregated forms of the beta-amyloid
      peptides beta(1-40) and beta(25-35), giving rise to a shift in the
      electrophoretic mobility of DNA. As a result, DNA was retained at the top of a 1%
      agarose gel. In contrast, the electrophoretic mobility of DNA was little
      influenced by the monomeric forms of beta(1-40) and beta(25-30). DNA from
      different sources such as lambda phage, Escherichia coli plasmid, and human gene
      showed similar results. However, the electrophoretic mobility of RNA was shifted
      by the monomeric beta(1-40) and beta(25-35) as well as by the aggregated beta(1
      40) and beta(25-35). The association of DNA with the aggregated beta-amyloid
      peptides could occur at pH 4-9. The inhibitory action of hemin on beta-amyloid
      aggregation could be confirmed using the DNA mobility shift assay. These results
      indicate that the DNA mobility shift assay is useful for kinetic study of beta
      amyloid aggregation as well as for testing of agents that might modulate beta
      amyloid aggregation.

PMID- 10964427
TI  - An efficient and cost-effective procedure for preparing samples for differential
      scanning calorimetry experiments.

PMID- 10964428
TI  - Internal Alu-polymerase chain reaction: a sensitive contamination monitoring
      protocol for DNA extracted from prehistoric animal bones.

PMID- 10964429
TI  - Colony assay for phage-displayed libraries.

PMID- 10964430
TI  - Characterization of the affinity of streptavidin toward a peptide sequence
      previously identified as a target substrate for biotinylation by the escherichia
      coli biotin holoenzyme synthetase, BirA.

PMID- 10964431
TI  - Calibration of colorimetric protein assays for quantitation of plant AB toxins.

PMID- 10964432
TI  - Quantitation of mRNA using in vitro RNA amplification and northern hybridization.

PMID- 10964433
TI  - Characterization of a polyclonal antihapten antibody by affinity capillary
      electrophoresis.

PMID- 10964434
TI  - A high-throughput screen to identify inhibitors of aromatase (CYP19).

PMID- 10964435
TI  - Carrier-linked peptides as a reference compound in enzyme-linked immunosorbent
      assays.

PMID- 10964436
TI  - Desalting of in-gel-digested protein sample with mini-C18 columns for matrix
      assisted laser desorption ionization time of flight peptide mass fingerprinting.

PMID- 10964437
TI  - A transient assay reveals that cultured human cells can accommodate multiple LINE
      1 retrotransposition events.

PMID- 10964438
TI  - Forster distances between green fluorescent protein pairs.

PMID- 10964439
TI  - Inactivation and clearance of viruses during the manufacture of high purity
      factor IX.
AB  - Haemophilia is a bleeding disorder characterised by a deficiency in Factor IX.
      Replacement therapy in the form of a Factor IX concentrate is a widely accepted
      practice. In this paper we describe a double virus inactivated chromatographic
      process for producing a high purity Factor IX product, MonoFIX((R))-VF. The
      process involves separation of the prothrombin complex by cryoprecipitation,
      fraction I precipitation and DEAE-cellulose adsorption, further ion-exchange
      chromatography of crude Factor IX, followed by solvent/detergent treatment.
      Heparin affinity chromatography is then used to further purify Factor IX. Final
      nanofiltration is sequential through 35 nm then 15 nm membrane filters. The
      principal virus inactivation/removal steps are solvent/detergent treatment and
      nanofiltration and the partitioning of relevant and model viruses provides
      further reduction in virus load through the production process.Solvent/detergent
      treatment was shown to achieve log reduction factors of 4.5 for HIV-1, 5.1 for
      Sindbis virus, 6.1 for vesicular stomatitis virus (VSV), 5.1 for bovine viral
      diarrhoea virus (BVDV) and 5.3 for pseudorabies virus (PRV). BVDV is a model for
      hepatitis C virus (HCV), and pseudorabies virus (PRV), like hepatitis B virus
      (HBV) is an enveloped DNA virus. Using scaled down models of the production
      process, we have also demonstrated the neutralization/partitioning of at least 6
      logs of hepatitis A virus (HAV) during cryoprecipitation, Fraction I
      precipitation, and the DEAE adsorption and elution step, and a further 1.6 log
      reduction in HAV load as a result of heparin affinity chromatography. The log
      reduction factors for HAV as a result of the second ion-exchange chromatography
      step and as a result of enhanced neutralisation associated with solvent/detergent
      treatment were not significant. Nanofiltration was shown to contribute a further
      log reduction factor of 6.7 for HAV and 5.8 for BVDV indicating that log
      reduction factors of this order would be obtained with other viruses of a similar
      or larger size, such as HIV, HBV and HCV.Overall, these studies indicate that
      MonoFIX-VF is a product with an extremely high level of viral safety.

PMID- 10964440
TI  - Real-time quantitative PCR for retrovirus-like particle quantification in CHO
      cell culture.
AB  - Chinese hamster ovary (CHO) cells have been widely used to manufacture
      recombinant proteins intended for human therapeutic uses. Retrovirus-like
      particles, which are apparently defective and non-infectious, have been detected
      in all CHO cells by electron microscopy (EM). To assure viral safety of CHO cell
      derived biologicals, quantification of retrovirus-like particles in production
      cell culture and demonstration of sufficient elimination of such retrovirus-like
      particles by the down-stream purification process are required for product market
      registration worldwide. EM, with a detection limit of 1x10(6) particles/ml, is
      the standard retrovirus-like particle quantification method. The whole process,
      which requires a large amount of sample (3-6 litres), is labour intensive, time
      consuming, expensive, and subject to significant assay variability. In this
      paper, a novel real-time quantitative PCR assay (TaqMan assay) has been developed
      for the quantification of retrovirus-like particles. Each retrovirus particle
      contains two copies of the viral genomic particle RNA (pRNA) molecule. Therefore,
      quantification of retrovirus particles can be achieved by quantifying the pRNA
      copy number, i.e. every two copies of retroviral pRNA is equivalent to one
      retrovirus-like particle. The TaqMan assay takes advantage of the 5'-->3'
      exonuclease activity of Taq DNA polymerase and utilizes the PRISM 7700 Sequence
      Detection System of PE Applied Biosystems (Foster City, CA, U.S.A.) for automated
      pRNA quantification through a dual-labelled fluorogenic probe. The TaqMan
      quantification technique is highly comparable to the EM analysis. In addition, it
      offers significant advantages over the EM analysis, such as a higher sensitivity
      of less than 600 particles/ml, greater accuracy and reliability, higher sample
      throughput, more flexibility and lower cost. Therefore, the TaqMan assay should
      be used as a substitute for EM analysis for retrovirus-like particle
      quantification in CHO cell-based production system.

PMID- 10964441
TI  - Development and validation of a detection system for wild-type Vibrio cholerae in
      genetically modified cholera vaccine.
AB  - Orochol, a live oral cholera vaccine licensed in Switzerland and in other
      countries, is based on the genetically modified Vibrio cholerae strain CVD103
      HgR. This strain is derived from the wild-type O1 strain Inaba 569B by deletion
      of a fragment internal to the ctxA gene encoding the A1 subunit of cholera toxin
      and by replacement of an internal fragment of the hlyA gene with a fragment
      carrying the mer operon mediating mercury resistance. In this study we describe a
      polymerase chain reaction (PCR) system for the detection of wild-type Vibrio
      cholerae and the identification of the vaccine strain for the quality control of
      production batches. A multiplex PCR system that targets the intact ctxA gene of
      the wild-type strain and simultaneously the integration site of the mer operon in
      the hlyA gene (hlyA::mer) of the vaccine strain CVD103-HgR was developed. To
      evaluate the detection limit of the system, vaccine suspensions were artificially
      contaminated with wild-type V. cholerae 569B cells and tested by PCR. The
      detection limit of the system was statistically evaluated and found to be at
      11625 wild-type cells per vaccine sachet (95% confidence limit). This number is
      below the infective dose of wild-type Vibrio cholerae. In Switzerland this test
      is used in combination with other tests in the official batch-release procedure
      to assure the safety of each batch of the cholera vaccine Orochol.

PMID- 10964442
TI  - Evaluation of the applicability of the bacterial endotoxin test to antibiotic
      products.
AB  - Fundamental conditions for applying the bacterial endotoxin test to antibiotic
      products were investigated so as not to affect the level of regulation by the
      rabbit pyrogen test. According to accuracy evaluation of test methods, the
      kinetic-turbidimetric and kinetic-colourimetric assays were shown to allow more
      accurate measurement and, therefore, more sensitive detection of interference to
      the bacterial endotoxin test than the gel-clot method. In total, 102 antibiotic
      products were evaluated on their interfering effect to show that the antibiotics
      could be categorized into three groups depending on intensity of the
      interference. Although the test was shown to be applicable even to the group
      showing the strongest interference, it was assumed to be crucial to use
      appropriate reagents and an accurate test method for avoiding approval of a
      pyrogenic product. Accordingly, lists of antibiotics are presented to provide
      limits of concentration for eliminating interference and endotoxin limits for
      approval to facilitate effective bacterial endotoxin tests.

PMID- 10964443
TI  - The removal of viruses during the purification of equine antisera using
      filtration aids Hyflo Super-Cel and Fulmon Super A.
AB  - The manufacturing process in Australia for equine antisera against various
      venoms/toxins is based primarily on ammonium sulphate precipitation of pepsin
      digested IgG, whereby Fc and F(ab')(2)fragments are separated. The capacity of
      the process to remove non-enveloped and enveloped model viruses was assessed
      using a scaled-down process. Each virus was added to mid-process samples from
      equine plasma before the material was applied to Hyflo Super-Celtrade mark
      filtration followed by Fulmonttrade mark Super A filtration. Samples were
      analysed pre- and post-filtration and the log clearance of the viruses
      calculated. The mean clearance factors for viral load of canine adenovirus type
      II (CAV(2)), poliovirus type 1 (PV1), infectious bovine rhinotracheitis virus
      (IBR) and canine distemper virus (CDV) were 5.3 logs, 4.2 logs, 5.7 logs and 4. 0
      logs respectively. Clearance results as virus is adsorbed to the filtration aids
      which are removed from the process, thereby demonstrating improved viral safety
      of equine antisera produced by CSL.

PMID- 10964444
TI  - An NMR spectroscopic identity test for the control of the capsular polysaccharide
      from Haemophilus influenzae type b.
AB  - We describe the use of Nuclear Magnetic Resonance (NMR) spectroscopy to control
      the identity of purified bulk capsular polysaccharide [called
      poly(ribosylribitolphosphate) or PRP] from Haemophilus influenzae type b (Hib),
      and derivatised forms, used in the production of Hib polysaccharide-protein
      conjugate vaccines. We describe the approaches we have developed to validate this
      test.

PMID- 10964445
TI  - Comparison of the inactivation of canine and bovine parvovirus by freeze-drying
      and dry-heat treatment in two high purity factor VIII concentrates.
AB  - The inactivation of bovine parvovirus (BPV) and canine parvovirus (CPV) by freeze
      drying and terminal dry-heat treatment at 80 degrees C for 72 h has been
      investigated in two high purity factor VIII concentrates. In one product, CPV was
      slightly more resistant to freeze-drying compared to BPV, i.e. 0.7 vs. 1.4 log.
      However, BPV was substantially more resistant to heat-treatment compared to CPV,
      i.e. 1.3 vs. > 3.1 log inactivation after 72 h at 80 degrees C. In a second
      product, CPV was also slightly more resistant to freeze-drying than BPV, i.e. 0.2
      vs. 1.3 log inactivation. However, heat-treatment gave essentially similar
      inactivation for both viruses, i.e. 2.8-3.4 log after 72 h at 80 degrees C. In
      conclusion, the resistance of these parvovirus models is dependent both on the
      type of virus and on the specific product involved.

PMID- 10964446
TI  - International workshop on clearance of TSE agents from blood products and
      implanted tissues.

PMID- 10964448
TI  - WHO Expert Committee on Biological Standardization: highlights of the 50th
      meeting, October 1999.
AB  - Biological medicines, which include vaccines, blood products and biological
      therapeutics, have historically played a dominant role in improving world health
      and are expected to make an increasingly important contribution to public health
      in the 21st century. Recent scientific and biotechnological developments have
      opened the way to novel products, new production methods and to highly sensitive
      assay procedures. However, the nature of biologicals, and especially new
      vaccines, blood products and therapeutics, raises particular questions regarding
      their standardization and quality control. These relate both to efficacy and to
      safety not only for the individual recipient but also for the population at
      large. Such advances highlight the complex issues surrounding standardization and
      control of biologicals, issues that need to be addressed on an international
      level.

PMID- 10964447
TI  - Standardisation and validation of serological assays for the evaluation of immune
      responses to Neisseria meningitidis serogroup A and C vaccines.

PMID- 10964449
TI  - My thanks, and an offer

PMID- 10964450
TI  - Role of phosphorylation of the cytoplasmic domain of the alpha(2)-macroglobulin
      receptor (LRP).
AB  - The low density lipoprotein receptor-related protein (alpha(2)MR/LRP) is a cell
      surface receptor which is present on most cells and tissues. We show that the 85
      kDa subunit, containing the transmembrane region and cytoplasmic domain is
      phosphorylated in vivo. Comparison of the phosphorylation of the low density
      lipoprotein receptor (LDLR) with a chimeric receptor containing the cytoplasmic
      domain of the alpha(2)MR/LRP (LDLR/LRP) showed that phosphorylation is exclusive
      to the cytoplasmic domain. Staurosporine, a general kinase inhibitor, resulted in
      a 40% lowering of phosphorylation of LDLR/LRP, but did not give rise to
      measurable changes in its membrane traffic in MDCK cells. The role of
      phosphorylation on degradation of the receptor was studied using inhibitors of
      lysosomal and proteasomal degradation. These studies showed that LDLR/LRP was
      rapidly turned over by proteasomal degradation but that this turnover was also
      not a consequence of phosphorylation.

PMID- 10964451
TI  - Centrosome alterations induced by formamide cause abnormal spindle pole
      formations.
AB  - The formation of the bipolar mitotic apparatus depends on accurate centrosome
      organization which is crucial for the separation of the genome during cell
      division. While it has been shown that mutations and overexpression of centrosome
      proteins (Brinkley and Goepfert, 1998; Pihan et al., 1998) can cause abnormal
      spindle pole formation, here we report that damages to centrosome structure
      caused by the chaotropic agent formamide will cause multipolar mitoses upon
      recovery from the effect when applied at first cell division in sea urchin eggs.
      Formamide was used as a chemical tool to manipulate centrosome structure and to
      investigate the effects on microtubule organization. When 1-1.5 m formamide was
      administered for 30 min at prometaphase of first cell division, microtubules were
      disassembled and centrosomes compacted into dense spheres around highly condensed
      chromatin. Upon recovery from formamide, centrosomes decompacted and attempted to
      form various mitotic organizations. Normal recovery (and attempts of recovery) to
      bipolarity was possible in five percent of cells treated with 1-1.5 m formamide
      for 30 min, but abnormal patterns of spindle formation were observed in all other
      cells, which included mono- (20%), tri (45%), and multipolar (30%) formations
      organized by mono-, tri-, and multipolar centrosome clusters. When cells were
      treated with 1.5 m formamide for 90 min, centrosomes became pulverized and
      fragmented and only monopolar mitotic formations were observed upon recovery.
      These results are highly reproducible and reveal that abnormalities in centrosome
      structure can lead to abnormal mitosis which is not caused by mutation or
      overexpression of centrosome proteins.

PMID- 10964452
TI  - Polyploid giant cells provide a survival mechanism for p53 mutant cells after DNA
      damage.
AB  - The relationships between delayed apoptosis, polyploid 'giant' cells and
      reproductive survivors were studied in p53-mutated lymphoma cells after DNA
      damage. Following severe genotoxic insult with irradiation or chemotherapy, cells
      arrest at the G(2)-M cell cycle check-point for up to 5 days before undergoing a
      few rounds of aberrant mitoses. The cells then enter endoreduplication cycles
      resulting in the formation of polyploid giant cells. Subsequently the majority of
      the giant cells die, providing the main source of delayed apoptosis; however, a
      small proportion survives. Kinetic analyses show a reciprocal relationship
      between the polyploid cells and the diploid stem line, with the stem line
      suppressed during polyploid cell formation and restituted after giant cell
      disintegration. The restituted cell-line behaves with identical kinetics to the
      parent line, once re-irradiated. When giant cells are isolated and followed in
      labelling experiments, the clonogenic survivors appear to arise from these cells.
      These findings imply that an exchange exists between the endocyclic (polyploid)
      and mitotic (diploid or tetraploid) populations during the restitution period and
      that giant cells are not always reproductively dead as previously supposed. We
      propose that the formation of giant cells and their subsequent complex breakdown
      and subnuclear reorganization may represent an important response of p53-mutated
      tumours to DNA damaging agents and provide tumours with a mechanism of repair and
      resistance to such treatments.

PMID- 10964453
TI  - Release of mitotic descendants by giant cells from irradiated Burkitt's lymphoma
      cell line..
AB  - Polyploid giant cells are produced as part of the response of p53 mutant
      Burkitt's lymphoma cell lines to high doses of irradiation. Polyploid giant cells
      arise by endo-reduplication in the first week after a single 10 Gray dose of
      irradiation. Within the giant cells a sub-nuclear structure is apparent and
      within this, sub-nuclear autonomy is evident, as displayed by independent nuclear
      structure and DNA replication in different parts of the nucleus. The majority of
      these cells soon die as apoptotic polykaryons. However, approximately 10-20% of
      giant cells remain viable into the second week after irradiation and begin
      vigorous extrusion of large degraded chromatin masses. During the second week,
      the giant cells begin to reconstruct their nuclei into polyploid 'bouquets',
      where chromosome double-loops are formed. Subsequently, the bouquets return to an
      interphase state and separate into several secondary nuclei. The individual sub
      nuclei then resume DNA synthesis with mitotic divisions and sequester cytoplasmic
      territories around themselves, giving rise to the secondary cells, which continue
      mitotic propagation. This process of giant cell formation, reorganization and
      breakdown appears to provide an additional mechanism for repairing double-strand
      DNA breaks within tumour cells.

PMID- 10964454
TI  - Structural association of Bax with nuclear matrix and cytomatrix revealed by
      embedment-free immunogold electron microscopy.
AB  - Bax is a cellular protein functioning as a promoter of apoptosis. It is
      ultrastructurally associated with mitochondrial membranes, where it participates
      in permeability transition pore formation. By employing embedment-free electron
      microscopy (EFEM), we present evidence that Bax is also associated with the
      nuclear matrix and cytomatrix of cultured human tumour cells (COLO 205, PA-1, U
      373 MG). Extracted cellular scaffolds were probed with anti-Bax antibody using
      the immunogold electron microscopy technique. Bax immunoreactivity was found on
      10-15 nm intermediate filaments of karyo- and cytoskeleton, stretched between the
      nucleus, nuclear lamina and cell periphery. Bax immunoreactivity was
      preferentially localized to certain areas of filaments (spot-like). The target
      molecules for Bax binding in the cellular matrix and their physiological
      significance remain to be established.

PMID- 10964455
TI  - Use of anti-single-stranded DNA antibodies to localize and quantify denatured DNA
      during cell death.

PMID- 10964456
TI  - Preschool children's use of trait labels to make inductive inferences.
AB  - One hundred one preschool children (ages 3 years 5 months to 4 years 10 months)
      participated in 3 studies examining the tendency to use verbal labels versus
      appearance information in making novel inductive inferences. A triad task
      analogous to that of S. A. Gelman and E. M. Markman (1986) was devised.
      Participants learned a different property for each of 2 children, and were asked
      which of the properties was true of a third child. One of the first 2 children
      was identified with the same label as the third child (e.g., both were labeled as
      shy) but looked different, and the other was identified with a different label
      than the third child but looked very similar. Results of Study 1 revealed that
      participants tended to use the trait labels, rather than superficial resemblance,
      in making psychological inferences. Studies 2 and 3 suggest that these results
      cannot be attributed to biases on the task. Study 4 provided a replication of the
      results of Study 1 in a context in which appearance information was explicitly
      pointed out and in which different trait labels were used.

PMID- 10964457
TI  - What do infants know about continuous quantity?
AB  - We investigated infants' sensitivity to amount of continuous quantity and to
      change in amount of continuous quantity. Using a habituation procedure,
      Experiment 1 examined whether 6-month-old infants can distinguish between
      different amounts of liquid in a container. Infants looked significantly longer
      at a novel quantity than at the familiar quantity. Using a violation-of
      expectation paradigm, Experiment 2 examined whether 9-month-old infants expect a
      change in amount when liquid is added to a hidden container which is already one
      fourth full of liquid. Infants looked significantly longer at the impossible
      event than at the possible event. These findings indicate that infants are
      sensitive to amount, calling into question claims that infants have a
      quantitative mechanism which is exclusive to number.

PMID- 10964459
TI  - Developmental changes in children's abilities to share and allocate attention in
      a dual task.
AB  - Characterizing developmental changes in children's dual-task performance has been
      problematic because differences in divided attention abilities are easily
      confounded with differences in overall capacity. Two experiments showed that
      after individual differences in children's capacity for single-task performance
      were controlled for, age differences between second- (M = 8.1 years) and fifth
      grade (M = 11.1 years) children did not exist in dual-task performance when tasks
      were of equal priority. However, when tasks had different priorities, only fifth
      grade children could differentially allocate attention in the dual task. Results
      are discussed within the coordination hypothesis framework (see A. F. Kramer & J.
      L. Larish, 1996), which suggests that changes in dual-task performance with aging
      are due to changes in the ability to coordinate and control the allocation of
      attention. It is argued that linking the investigations of children's attention
      with research on attention and aging provides both methodological and theoretical
      benefits.

PMID- 10964458
TI  - Language deficits in dyslexic children: speech perception, phonology, and
      morphology.
AB  - We investigated the relationship between dyslexia and three aspects of language:
      speech perception, phonology, and morphology. Reading and language tasks were
      administered to dyslexics aged 8-9 years and to two normal reader groups (age
      matched and reading-level matched). Three dyslexic groups were identified:
      phonological dyslexics (PD), developmentally language impaired (LI), and globally
      delayed (delay-type dyslexics). The LI and PD groups exhibited similar patterns
      of reading impairment, attributed to low phonological skills. However, only the
      LI group showed clear speech perception deficits, suggesting that such deficits
      affect only a subset of dyslexics. Results also indicated phonological
      impairments in children whose speech perception was normal. Both the LI and the
      PD groups showed inflectional morphology difficulties, with the impairment being
      more severe in the LI group. The delay group's reading and language skills
      closely matched those of younger normal readers, suggesting these children had a
      general delay in reading and language skills, rather than a specific phonological
      impairment. The results are discussed in terms of models of word recognition and
      dyslexia.

PMID- 10964460
TI  - Sperm-induced Ca(2+) oscillations in mouse oocytes and eggs can be mimicked by
      photolysis of caged inositol 1,4,5-trisphosphate: evidence to support a
      continuous low level production of inositol 1, 4,5-trisphosphate during mammalian
      fertilization.
AB  - During mouse fertilization the spermatozoon induces a series of low-frequency
      long-lasting Ca(2+) oscillations. It is generally accepted that these
      oscillations are due to Ca(2+) release through the inositol 1,4,5-trisphosphate
      (InsP(3)) receptor. However, InsP(3) microinjection does not mimic sperm-induced
      Ca(2+) oscillations, leading to the suggestion that the spermatozoon causes
      Ca(2+) release by sensitizing the InsP(3) receptor to basal levels of InsP(3).
      This contradicts recent evidence that the spermatozoon triggers Ca(2+)
      oscillations by introducing a phospholipase C or else an activator of
      phospholipase C. Here we show for the first time that sperm-induced Ca(2+)
      oscillations may be mimicked by the photolysis of caged InsP(3) in both mouse
      metaphase II eggs and germinal vesicle stage oocytes. Eggs, and also oocytes that
      had displayed spontaneous Ca(2+) oscillations, gave long-lasting Ca(2+)
      oscillations when fertilized or when caged InsP(3) was photolyzed. In contrast,
      oocytes that had shown no spontaneous Ca(2+) oscillations did not generate many
      oscillations when fertilized or following photolysis of caged InsP(3).
      Fertilization in eggs was most closely mimicked when InsP(3) was uncaged at
      relatively low amounts for extended periods. Here we observed an initial Ca(2+)
      transient with superimposed spikes, followed by a series of single transients
      with a low frequency; all characteristics of the Ca(2+) changes at fertilization.
      We therefore show that InsP(3) can mimic the distinctive pattern of Ca(2+)
      release in mammalian eggs at fertilization. It is proposed that a sperm Ca(2+)
      releasing factor operates by generating a continuous small amount of InsP(3) over
      an extended period of time, consistent with the evidence for the involvement of a
      phospholipase C.

PMID- 10964461
TI  - Cellular basis of the dynamic behavior of the imaginal thoracic discs during
      Drosophila metamorphosis.
AB  - The eversion, migration, spreading, and fusion of the thoracic imaginal discs
      during metamorphosis of Drosophila are described using timed whole-mount
      preparations and several molecular markers. The leading edge of the migrating
      disc epithelia consists of two groups of cells, stalk cells (S cells) and
      specialized imaginal cells (I cells), that both express the gene puckered. With
      this and other markers, opening of the stalk, eversion of the discs, migration of
      the leading edges, and fusion of the imaginal epithelia can be visualized in
      detail. Fusion is initiated by S cells that migrate over the larval epithelium
      and constitute a bridge between two imaginal epithelia. S cells are subsequently
      lost and imaginal fusion is mediated by the I cells that remain at the site of
      fusion. The possible cellular basis of this process is discussed. Fusion along
      the dorsal midline of the notum from the mesothoracic wing discs occurs earlier
      than that of the prothoracic and metathoracic discs, which remain in a lateral
      position. For a relatively long period (30 h) the mesothoracic epithelium becomes
      attached to the head and abdomen, causing a temporary local discontinuity of the
      order of segments. Later the pro- and metathoracic discs intercalate between head
      and mesothorax and between abdomen and mesothorax, respectively, to reestablish
      the normal order.

PMID- 10964462
TI  - Defective mesonephric cell migration is associated with abnormal testis cord
      development in C57BL/6J XY(Mus domesticus) mice.
AB  - During the critical period of mouse sex determination, mesenchymal cells migrate
      from the mesonephros into the adjacent developing testis. This process is thought
      to initiate cord development and is dependent on Sry. The presence of Sry,
      however, does not always guarantee normal testis development. For example,
      transfer of certain Mus domesticus-derived Y chromosomes, i.e., M. domesticus Sry
      alleles, onto the C57BL/6J (B6) inbred mouse strain results in abnormal testis
      development. We tested the hypothesis that mesonephric cell migration was
      impaired in three cases representing a range of aberrant testis development: B6
      XY(AKR), B6 XY(POS), and (BXD-21 x B6-Y(POS))F1 XY(POS). In each case,
      mesonephric cell migration was abnormal. Furthermore, the timing, extent, and
      position of migrating cells in vitro and cord development in vivo were
      coincident, supporting the hypothesis that mesonephric cells are critical for
      cord development. Additional experiments indicated that aberrant testis
      development results from the inability of Sry(M. domesticus) to initiate normal
      cell migration, but that downstream signal transduction mechanisms are intact.
      These experiments provide new insight into the mechanism of C57BL/6J-Y(M.
      domesticus) sex reversal. We present a model incorporating these findings as they
      relate to mammalian sex determination.

PMID- 10964463
TI  - Designation of the anterior/posterior axis in pregastrula Xenopus laevis.
AB  - A new fate map for mesodermal tissues in Xenopus laevis predicted that the prime
      meridian, which runs from the animal pole to the vegetal pole through the center
      of Spemann's organizer, is the embryo's anterior midline, not its dorsal midline
      (M. C. Lane and W. C. Smith, 1999, Development 126, 423-434). In this report, we
      demonstrate by lineage labeling that the column 1 blastomeres at st. 6, which
      populate the prime meridian, give rise to the anterior end of the embryo. In
      addition, we surgically isolate and culture tissue centered on this meridian from
      early gastrulae. This tissue forms a patterned head with morphologically distinct
      ventral and dorsal structures. In situ hybridization and immunostaining reveal
      that the cultured heads contain the anterior tissues of all three germ layers,
      correctly patterned. Regardless of how we dissect early gastrulae along meridians
      running from the animal to the vegetal pole, both the formation of head
      structures and the expression of anterior marker genes always segregate with the
      prime meridian passing through Spemann's organizer. The prime meridian also gives
      rise to dorsal, axial mesoderm, but not uniquely, as specification tests show
      that dorsal mesoderm arises in fragments of the embryo which exclude the prime
      meridian. These results support the hypothesis that the midline that bisects
      Spemann's organizer is the embryo's anterior midline.

PMID- 10964464
TI  - Different isoforms of fasciclin II play distinct roles in the guidance of
      neuronal migration during insect embryogenesis.
AB  - During the formation of the enteric nervous system (ENS) of the moth Manduca
      sexta, identified populations of neurons and glial cells participate in precisely
      timed waves of migration. The cell adhesion receptor fasciclin II is expressed in
      the developing ENS and is required for normal migration. Previously, we
      identified two isoforms of Manduca fasciclin II (MFas II), a glycosyl
      phosphatidylinositol-linked isoform (GPI-MFas II) and a transmembrane isoform (TM
      MFas II). Using RNA and antibody probes, we found that these two isoforms were
      expressed in cell type-specific patterns: GPI-MFas II was expressed by glial
      cells and newly generated neurons, while TM-MFas II was confined to
      differentiating neurons. The expression of each isoform also corresponded to the
      motile state of the different cell types: GPI-MFas II was detected on tightly
      adherent or slowly spreading cells, while TM-MFas II was expressed by actively
      migrating neurons and was localized to their most motile regions. Manipulations
      of each isoform in embryo culture showed that they played distinct roles: whereas
      GPI-MFas II acted strictly as an adhesion molecule, TM-MFas II promoted the
      motility of the EP cells as well as maintaining fasciculation with their
      pathways. These results indicate that precisely regulated patterns of isoform
      expression govern the functions of fasciclin II within the developing nervous
      system.

PMID- 10964465
TI  - The development and subsequent elimination of aberrant peripheral axon
      projections in Semaphorin3A null mutant mice.
AB  - Semaphorin3A (previously known as Semaphorin III, Semaphorin D, or collapsin-1)
      is a member of the semaphorin gene family, many of which have been shown to guide
      axons during nervous system development. Semaphorin3A has been demonstrated to be
      a diffusible chemorepulsive molecule for axons of selected neuronal populations
      in vitro. Analysis of embryogenesis in two independent lines of Semaphorin3A
      knockout mice support the hypothesis that this molecule is an important guidance
      signal for neurons of the peripheral nervous system (M. Taniguchi et al., 1997,
      Neuron 19, 519-530; E. Ulupinar et al., 1999, Mol. Cell. Neurosci. 13, 281-292).
      Surprisingly, newborn Semaphorin3A null mutant mice exhibit no significant
      abnormalities (O. Behar et al., 1996, Nature 383, 525-528). In this study we have
      tested the hypothesis that guidance abnormalities that occurred during early
      stages of Semaphorin3A null mice development are corrected later in development.
      We have found that the extensive abnormalities formed during early developmental
      stages in the peripheral nervous system are largely eliminated by embryonic day
      15.5. We demonstrate further that at least in one distinct anatomical location
      these abnormalities are mainly the result of aberrant projections. In conclusion,
      these findings suggest the existence of correction mechanisms that eliminate most
      sensory axon pathfinding errors early in development.

PMID- 10964466
TI  - Wound healing in jellyfish striated muscle involves rapid switching between two
      modes of cell motility and a change in the source of regulatory calcium.
AB  - Small wounds (1.2 mm in diameter) made in the sheet of myoepithelial cells
      forming the "swimming" muscle of the jellyfish, Polyorchis penicillatus, were
      closed within 10 h by epithelial cells migrating centripetally to the wound
      center. Some 24 to 48 h later these cells redifferentiated into fully contractile
      muscle cells. Labeling with bromodeoxyuridine failed to reveal any cell
      proliferation during this process. Phenotype switching (within 1 h) from
      contractile muscle cells to migratory cells did not require synthesis of new
      protein as shown by treatment with 40 microM cycloheximide. Excitation
      contraction coupling in undamaged muscle depended on entry of Ca(2+) through
      voltage-gated ion channels, as shown by a block of contractility by 40 microM
      nitrendipine and also on calcium released from intracellular stores since
      caffeine (10 mM) caused a 25% reduction in contractile force. In contrast,
      migratory cells did not require a source of extracellular calcium since migration
      was unimpeded by low (1 microM) free Ca(2+) or nitrendipine. Instead, modulatory
      calcium was derived from intracellular stores since caffeine (10 mM) and
      thapsigargin (10 microM) slowed migration. This lack of dependence on calcium
      influx in migratory cells was further confirmed by a dramatic down-regulation in
      voltage-gated inward current as shown by whole-cell patch recordings.

PMID- 10964467
TI  - Calmodulin and immunophilin are required as functional partners of a ryanodine
      receptor in ascidian oocytes at fertilization.
AB  - Fertilization of oocytes incites numerous changes relying on Ca(2+) signaling. In
      inseminated ascidian eggs, an increase in the egg surface membrane, monitored by
      a change in electrical capacitance, is recorded at the onset of meiosis
      resumption. This membrane addition to the cell surface is controlled by calcium
      release through a ryanodine receptor (RyR), sensitive to cyclic ADP-ribose. Using
      confocal microscopy analysis of ascidian oocytes immunostained with anti-RyR
      antibody, we show here that this calcium channel is asymmetrically located in the
      vegetal cortical zone. Interestingly, the increase in cell capacitance occurring
      at fertilization is correlated with a fluorescent signal, imaged by the marker of
      vesicle trafficking FM 1-43, located close to the RyR region. Two putative
      partners of RyR, namely an FKBP-like protein and a calmodulin, are identified in
      these oocyte extracts by detection of enzyme activity and PCR amplification. Both
      are necessary to sustain ryanodine receptor activity in these oocytes since the
      membrane insertion triggered by fertilization is inhibited by the FKBP ligand
      rapamycin and by a calmodulin antagonist peptide. These findings suggest that
      exocytosis in ascidian eggs is triggered at fertilization by a functional Ca(2+)
      release unit operating as a complex of several proteins, including a calmodulin
      and an immunophilin, around the intracellular calcium channel itself.

PMID- 10964468
TI  - Differences in spindle association of the mitotic checkpoint protein Mad2 in
      mammalian spermatogenesis and oogenesis.
AB  - We have investigated expression and subcellular localization of the spindle
      checkpoint protein Mad2 during rat and mouse spermatogenesis and in superovulated
      mouse oocytes. Our immunofluorescence studies demonstrate substantial differences
      in the localization patterns of kinetochore-associated Mad2 in these meiotic
      systems compared with previous studies of mitosis. In addition, the association
      of Mad2 with second-division-metaphase kinetochores differed significantly in
      male versus female meiosis. In spermatogenesis, Mad2 remained at most
      kinetochores throughout the entire first meiotic division and was lost only at
      metaphase of the second meiotic division. This result indicates that loss of
      kinetochore-associated Mad2 is not essential for the metaphase-to-anaphase
      transition during the first meiotic division. Disruption of the male meiotic
      spindles with the microtubule depolymerizing agent nocodazole resulted in the
      appearance of Mad2 at nearly all kinetochores. In contrast, the microtubule
      stabilizer taxol induced the loss of Mad2 from the majority of the first-division
      metaphase kinetochores in which it was normally present in untreated cells. In
      contrast to the situation in spermatogenesis, Mad2 persisted at the kinetochores
      of normal, second-division oocytes at metaphase. These findings suggest that the
      role of the kinetochore in signaling in the spindle checkpoint may differ
      markedly between mammalian mitosis and meiosis, between the two meiotic
      divisions, and between male and female meiosis.

PMID- 10964469
TI  - A role for a TIMP-3-sensitive, Zn(2+)-dependent metalloprotease in mammalian
      gamete membrane fusion.
AB  - During fertilization, sperm and egg plasma membranes adhere and then fuse by a
      mechanism that is not well understood. Zinc metalloproteases are necessary for
      some intercellular fusion events, for instance, cell-cell fusion in yeast. In
      this study we tested the effects of class-specific and family-specific protease
      inhibitors on mouse gamete fusion. Capacitated, acrosome-reacted sperm and zona
      free eggs were used in assays designed to define the effects of inhibitors on
      sperm-egg plasma membrane binding or fusion. Inhibitors of the aspartic,
      cysteine, and serine protease classes had no effect on sperm-egg binding or
      fusion. Both a synthetic metalloprotease substrate (succinyl-Ala-Ala-Phe
      amidomethylcoumarin) and the zinc chelator 1,10-phenanthroline inhibited sperm
      egg fusion but did not decrease sperm-egg binding. The fusion-inhibition effect
      of phenanthroline was reversible and activity of the inhibitable zinc
      metalloprotease was shown to be required during a short time window, the first 15
      min after insemination. Tissue inhibitor of metalloprotease-3 and Ro 31-9790,
      specific inhibitors of zinc metalloproteases in the matrixin and adamalysin
      families, also inhibited sperm-egg fusion but not sperm-egg binding. These data
      indicate a role in gamete fusion for one or more zinc metalloproteases of the
      matrixin and/or adamalysin families that act after plasma membrane binding and
      before sperm-egg membrane fusion.

PMID- 10964472
TI  - Characterization of a maternal T-Box gene in Ciona intestinalis.
AB  - A new T-box gene, CiVegTR, was isolated in the ascidian Ciona intestinalis.
      CiVegTR maternal RNAs become localized to the vegetal cytoplasm of fertilized
      eggs and are incorporated into muscle lineages derived from the B4.1 blastomere.
      The CiVegTR protein binds to specific sequences within a minimal, 262-bp enhancer
      that mediates Ci-snail expression in the tail muscles. Mutations in these binding
      sites abolish expression from an otherwise normal lacZ reporter gene in
      electroporated embryos. In addition to the previously identified AC-core E-box
      sequences, T-box recognition sequences are conserved in the promoter regions of
      many genes expressed in B4.1 lineages in both Ciona and the distantly related
      ascidian Halocynthia. These results suggest that CiVegTR encodes a component of
      the classical muscle determinant that was first identified in ascidians nearly
      100 years ago.

PMID- 10964470
TI  - Separation of neural induction and neurulation in Xenopus.
AB  - Cellular interactions with laminin are important for numerous morphogenetic
      events. In Xenopus, the first of these is neurulation. The integrin alpha6
      subunit mediates an attachment of the cells of the neural plate to the underlying
      basal lamina. A disruption of this interaction results in embryos that fail to
      neurulate (T. E. Lallier et al., 1996, Development 122, 2539-2554). Here we
      provide evidence supporting the specificity of this phenomenon and characterize
      developmental events as either disrupted or unaffected by a perturbation of
      alpha6 integrin expression. First, reduction of alpha6 integrin expression does
      not halt mitotic division throughout the embryo, indicating that the neural
      defects observed are not simply a global perturbation of all developmental
      processes. Second, a gene associated with dorsal mesoderm formation, brachyury,
      is expressed normally in alpha6 integrin-perturbed embryos. Third, the expression
      of BMP4, noggin, chordin, and follistatin, all of which are critical for neural
      induction, are at near normal levels. In addition, several genes expressed
      shortly after neural induction (N-CAM, nrp1, and Xanf1) are not perturbed in
      nonneurulating embryos. Interestingly, expression of one neural-specific gene
      (synaptobrevin), which is normally detectable late in neurulation, is abolished
      in these alpha6 integrin-perturbed embryos. Furthermore, the spatial expression
      of several transcripts is expanded in alpha6 integrin-perturbed embryos
      (orthodenticle and engrailed). Taken together, these data indicate that while
      alpha6 integrin-mediated interactions with laminin are required for neurulation,
      they are not required for the initial processes of neural induction. However,
      these cell-extracellular matrix interactions appear to be important in later
      inductive events and rostrocaudal patterning of the neural tube.

PMID- 10964474
TI  - Endogenous and ectopic gland induction by FGF-10.
AB  - FGF-10, a member of the fibroblast growth factor family, is expressed in
      mesodermally derived cell populations during embryogenesis. During normal ocular
      development, FGF-10 is expressed in the perioptic mesenchyme adjacent to the
      Harderian and lacrimal gland primordia. In this report, we provide evidence that
      FGF-10 is both necessary and sufficient to initiate glandular morphogenesis. Lens
      specific expression of FGF-10 was sufficient to induce ectopic ocular glands
      within the cornea. In addition, lacrimal and Harderian glands were not seen in
      FGF-10 null fetuses. Based on these results we propose that FGF-10 is an
      inductive signal that initiates ocular gland morphogenesis.

PMID- 10964473
TI  - glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal
      development.
AB  - Glypicans represent a family of six cell surface heparan sulfate proteoglycans in
      vertebrates. Although no specific in vivo functions have thus far been described
      for these proteoglycans, spontaneous mutations in the human and induced deletions
      in the mouse glypican-3 (Gpc3) gene result in severe malformations and both pre-
      and postnatal overgrowth, known clinically as the Simpson-Golabi-Behmel syndrome
      (SGBS). Mice carrying mutant alleles of Gpc3 created by either targeted gene
      disruption or gene trapping display a wide range of phenotypes associated with
      SGBS including renal cystic dysplasia, ventral wall defects, and skeletal
      abnormalities that are consistent with the pattern of Gpc3 expression in the
      mouse embryo. Previous studies in Drosophila have implicated glypicans in the
      signaling of decapentaplegic, a BMP homolog. Our experiments with mice show a
      significant relationship between vertebrate BMP signaling and glypican function;
      GPC3-deficient animals were mated with mice haploinsufficient for bone
      morphogenetic protein-4 (Bmp4) and their offspring displayed a high penetrance of
      postaxial polydactyly and rib malformations not observed in either parent strain.
      This previously unknown link between glypican-3 and BMP4 function provides
      evidence of a role for glypicans in vertebrate limb patterning and skeletal
      development and suggests a mechanism for the skeletal defects seen in SGBS.

PMID- 10964477
TI  - Cells remain competent to respond to mesoderm-inducing signals present during
      gastrulation in Xenopus laevis.
AB  - During gastrulation, the vertebrate embryo is patterned and shaped by complex
      signaling pathways and morphogenetic movements. One of the first regions defined
      during gastrulation is the prospective notochord, which exhibits specific cell
      behaviors that drive the extension of the embryonic axis. To examine the signals
      involved in notochord formation in Xenopus laevis and the competence of cells to
      respond to these signals, we performed cell transplantation experiments during
      gastrulation. Labeled cells from the prospective notochord, somitic mesoderm,
      ventrolateral mesoderm, neural ectoderm, and epidermis, between stages 9
      (pregastrulation) and 12 (late gastrulation), were grafted into the prospective
      notochord region of the early gastrula. We show that cells from each region are
      competent to respond to notochord-inducing signals and differentiate into
      notochordal tissue. Cells from the prospective neural ectoderm are the most
      responsive to notochord-inducing signals, whereas cells from the ventrolateral
      and epidermal regions are the least responsive. We show that at the end of
      gastrulation, while transplanted cells lose their competence to form notochord,
      they remain competent to form somites. These results demonstrate that at the end
      of gastrulation cell fates are not restricted within germ layers. To determine
      whether notochord-inducing signals are present throughout gastrulation, grafts
      were made into progressively older host embryos. We found that regardless of the
      age of the host, grafted cells from each region give rise to notochordal tissue.
      This indicates that notochord-inducing signals are present throughout
      gastrulation and that these signals overlap with somite-inducing signals at the
      end of gastrulation. We conclude that it is the change of competence that
      restricts cells to specific tissues rather than the regulation of the inducing
      signals.

PMID- 10964471
TI  - Loss of late primitive streak mesoderm and interruption of left-right
      morphogenesis in the Ednrb(s-1Acrg) mutant mouse.
AB  - This study characterizes defects associated with abnormal mesoderm development in
      mouse embryos homozygous for the induced Ednrb(s-1Acrg) allele of the piebald
      deletion complex. The Ednrb(s-1Acrg) deletion results in recessive embryonic
      lethality and mutant embryos exhibit a truncated posterior body axis. The
      primitive streak and node become disfigured, consistent with evidence that cell
      migration is impaired in newly formed mesoderm. Additional defects related to
      mesoderm development include notochord degeneration, somite malformations, and
      abnormal vascular development. Arrested heart looping morphogenesis and a
      randomized direction of embryonic turning indicate that left-right development is
      also perturbed. The expression of nodal and leftb, Tgf-beta-related genes
      involved in a left-determinant signaling pathway, is variably lost in the left
      lateral plate mesoderm. Mutational analysis has demonstrated that Fgf8 and
      Brachyury (T) are required for normal mesoderm and left-right development and the
      asymmetric expression of nodal and leftb. Fgf8 expression in nascent mesoderm
      exiting the primitive streak is dramatically reduced in mutant embryos, and
      diminished T expression accompanies the progressive loss of paraxial, lateral,
      and primitive streak mesoderm. In contrast, axial mesoderm persists and T and
      nodal appear to be appropriately expressed in their specific domains in the node
      and notochord. We propose that this mutation disrupts a morphogenetic pathway,
      likely involving FGF signaling, important for the development of streak-derived
      posterior mesoderm and lateral morphogenesis.

PMID- 10964478
TI  - Spinal nerve segmentation in the chick embryo: analysis of distinct axon
      repulsive systems.
AB  - In higher vertebrates, the segmental organization of peripheral spinal nerves is
      established by a repulsive mechanism whereby sensory and motor axons are excluded
      from the posterior half-somite. A number of candidate axon repellents have been
      suggested to mediate this barrier to axon growth, including Sema3A, Ephrin-B, and
      peanut agglutinin (PNA)-binding proteins. We have tested the candidacy of these
      factors in vitro by examining their contribution to the growth cone collapse
      inducing activity of somite-derived protein extracts on sensory, motor, and
      retinal axons. We find that Sema3A is unlikely to play a role in the segmentation
      of sensory or motor axons and that Ephrin-B may contribute to motor but not
      sensory axon segmentation. We also provide evidence that the only candidate
      molecule(s) that induces the growth cone collapse of both sensory and motor axons
      binds to PNA and is not Sema3A or Ephrin-B. By grafting primary sensory, motor,
      and quail retinal neurons into the chick trunk in vivo, we provide further
      evidence that the posterior half-somite represents a universal barrier to growing
      axons. Taken together, these results suggest that the mechanisms of peripheral
      nerve segmentation should be considered in terms of repellent molecules in
      addition to the identified molecules.

PMID- 10964475
TI  - Expression of spicule matrix proteins in the sea urchin embryo during normal and
      experimentally altered spiculogenesis.
AB  - During its embryonic development, the sea urchin embryo forms an endoskeletal
      calcitic spicule. This instance of biomineralization is experimentally accessible
      and also offers the advantage of occurring within a developmental context. Here
      we investigate the time course of appearance and localization of two proteins
      among the four dozen that constitute the protein matrix of the skeletal spicule.
      SM50 and SM30 have been studied in some detail, and polyclonal antisera have been
      prepared against them (C. E. Killian and F. H. Wilt, 1996, J. Biol. Chem. 271,
      9150-9159). Using these antibodies we describe here the localization and time
      course of accumulation of these two proteins in Strongylocentrotus purpuratus,
      both in the intact embryo and in micromere cultures. We also investigate the
      disposition of the matrix proteins, SM50, SM30, and PM27, in the three
      dimensional spicule by studying changes in protein localization during
      experimental manipulation of isolated skeletal spicules. We conclude that SM50,
      PM27, and SM30 probably play different roles in biomineralization, based on their
      localization and patterns of expression. It is unlikely that these proteins are
      solely structural elements within the mineral. SM50 and PM27 may play a role in
      defining the extracellular space in which spicule deposition occurs, while SM30
      may play a role in secretion of spicule components. Finally, we report on the
      effects of serum on expression of some primary mesenchyme-specific proteins in
      micromere cultures; withholding serum severely depresses accumulation of SM30 but
      has only modest effects on the accumulation of other proteins.

PMID- 10964476
TI  - Staging of the commitment of murine cardiac cell progenitors.
AB  - The staging of murine cardiomyocyte specification and determination was
      investigated in cultures of tissue explants from pre- and postgastrulated embryos
      and after transplantation of cardiac or cardiogenic tissues from mouse embryos
      into 2-day-old chick embryos in different locations. The development of
      transplanted and cultured cells in cardiomyocytes was evaluated by testing the
      expression of several cardiac transcription factor genes (Nkx 2.5, eHAND, dHAND,
      GATA-4), alpha-cardiac actin mRNA, and beta-myosin heavy chain protein. In vitro
      analyses showed that cells with the potential to form cardiac muscle were present
      prior to gastrulation in 6.5-day postconception (dpc) epiblasts, as indicated by
      the expression of Nkx 2.5, eHAND, dHAND, and GATA-4 cardiac transcription
      factors; desmin transgene; alpha-cardiac actin; and beta-myosin heavy chain.
      Conversely, epiblasts transplanted into the chicken somitic environment did not
      exhibit full cardiogenic cell differentiation. It was determined that chick host
      axial structures did not influence cardiogenesis in transplants. Mesoderm from
      late streak explants was capable of differentiating into the cardiac phenotype in
      the avian heterotopic environment, indicating that the specification of cardiac
      precursors (under way by 6.5 dpc) became irreversible at around the late streak
      stage in mouse embryo. Although in vitro analyses showed that interaction with
      endoderm is not required for the specification of murine cardiac cells, the
      presence of endoderm in explant cultures between mid- and late streak stages
      stimulated emerging mesodermal cells to adopt a myocardial pathway, whereas
      ectoderm had no influence on cardiomyogenesis.

PMID- 10964479
TI  - Role of the Fyn kinase in calcium release during fertilization of the sea urchin
      egg.
AB  - Protein tyrosine kinase activity has been implicated as part of the signaling
      mechanism leading to the sperm-induced calcium transient following fertilization.
      In the present study, we have tested the role of the Fyn kinase in triggering the
      calcium transient by microinjecting domain-specific fusion proteins encoding
      regions of Fyn sequence as inhibitors of Fyn function in vivo. A fusion protein
      encoding the SH2 domain of Fyn caused an increase in the latent period between
      sperm-egg fusion and the beginning of the calcium transient and reduced the
      amplitude of the calcium signal. A fusion protein encoding the U + SH3 domains
      also caused a small increase in the latent period. Microscopic examination
      revealed that a large percentage of eggs injected with the U+SH3 or SH2 domains
      became polyspermic as a result of the delayed block to polyspermy. Affinity
      experiments demonstrated that the U+SH3 and SH2 domains of Fyn were capable of
      forming a stable complex with phospholipase Cgamma from the sea urchin egg. The
      results suggest that the Fyn kinase participates in the signaling events leading
      up to the calcium transient and may directly regulate phospholipase Cgamma
      activity at fertilization.

PMID- 10964480
TI  - Participation of par-4 in the degeneration of striatal neurons induced by
      metabolic compromise with 3-nitropropionic acid.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder
      characterized by chorea, psychiatric disturbances, and dementia. It is caused by
      a polyglutamine repeat expansion in the huntingtin protein. The striatum is a
      major site of neuronal loss in HD, but the mechanisms underlying the
      neurodegenerative process have not been established. Systemic administration of
      the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP) to rodents
      results in motor dysfunction and degeneration of striatal neurons with features
      similar to those of HD. Here we report that levels of prostate apoptosis response
      4 (Par-4; a protein recently linked to neuronal apoptosis) increase in striatum,
      and to a lesser extent in cortex and hippocampus, after systemic administration
      of 3NP to adult rats. The increase in Par-4 levels occurred within 6 h of 3NP
      administration and was followed by an increase in caspase activation which
      preceded neuronal loss. Exposure of cultured primary striatal neurons to 3NP
      induced a rapid increase of Par-4 levels and caspase activation. Treatment of
      striatal neurons with a Par-4 antisense oligonucleotide blocked Par-4 induction
      by 3NP, suppressed caspase activation, and attenuated neuronal apoptosis. The
      caspase-3 inhibitor DEVD suppressed 3NP-induced apoptosis of striatal neurons,
      but did not prevent induction of Par-4, indicating that Par-4 acts upstream of
      caspase-3 activation in the cell death pathway. Our results suggest that Par-4
      plays an important role in the degeneration of striatal neurons in an
      experimental model of HD.

PMID- 10964481
TI  - nNOS expression in reactive astrocytes correlates with increased cell death
      related DNA damage in the hippocampus and entorhinal cortex in Alzheimer's
      disease.
AB  - The immunocytochemical distribution of the neuronal form of nitric oxide synthase
      (nNOS) was compared with neuropathological changes and with cell death related
      DNA damage (as revealed by in situ end labeling, ISEL) in the hippocampal
      formation and entorhinal cortex of 12 age-matched control subjects and 12
      Alzheimer's disease (AD) patients. Unlike controls, numerous nNOS-positive
      reactive astrocytes were found in AD patients around beta-amyloid plaques in CA1
      and subiculum and at the places of clear and overt neuron loss, particularly in
      the entorhinal cortex layer II and CA4. This is the first evidence of nNOS-like
      immunoreactivity in reactive astrocytes in AD. In contrast to controls, in all
      but one AD subject, large numbers of ISEL-positive neuronal nuclei and microglial
      cells were found in the CA1 and CA4 regions and subiculum. Semiquantitative
      analysis showed that neuronal DNA fragmentation in AD match with the distribution
      of nNOS-expressing reactive astroglial cells in CA1 (r = 0.74, P < 0.01) and CA4
      (r = 0.58, P < 0.05). A portion of the nNOS-positive CA2/CA3 pyramidal neurons
      was found to be spared even in the most affected hippocampi. A significant
      inverse correlation between nNOS expression and immunoreactivity to abnormally
      phosphorylated tau proteins (as revealed by AT8 monoclonal antibody) in perikarya
      of these CA2/3 neurons (r = -0.85, P < 0.01) suggests that nNOS expression may
      provide selective resistance to neuronal degeneration in AD. In conclusion, our
      results imply that an upregulated production of NO by reactive astrocytes may
      play a key role in the pathogenesis of AD.

PMID- 10964482
TI  - Human amniotic epithelial cells produce dopamine and survive after implantation
      into the striatum of a rat model of Parkinson's disease: a potential source of
      donor for transplantation therapy.
AB  - We have recently found that human amniotic epithelial (HAE) cells synthesize
      catecholamines including dopamine (DA). The present study was designed to explore
      the possibility of HAE cells to serve as a donor for transplantation therapy of
      Parkinson's disease (PD). Thus, we investigated their ability to produce DA in
      vitro and the survival and function of HAE cells grafted into a rat model of PD.
      RT-PCR and Western blotting revealed that HAE cells express tyrosine hydroxylase
      (TH) mRNA and protein, respectively. TH-immunohistochemistry on cultured HAE
      cells demonstrated that around 10% of the total cells are immunopositive for this
      protein. The production of DA by HAE cells was increased with time in the
      presence of L-tyrosine and BH(4), and was abolished with a specific TH inhibitor,
      alpha-methyl-rho-tyrosine. Dissociated HAE cells transduced with the Escherichia
      coli LacZ marker gene (beta-gal) were implanted into the previously DA-depleted
      striatum of immunosuppressed rats. Two weeks postgrafting HAE grafts were
      demonstrated to survive without overgrowth, as evidenced by the presence of beta
      gal-positive cells and TH-immunoreactive cells within the grafts. The grafts also
      provided partial amelioration of apomorphine-induced rotational asymmetry. The
      results clearly indicate that HAE cells capable of producing DA can survive and
      function in the brain of a rat model of PD. Although DA replacement therapy of PD
      could possibly be achieved with implantation of HAE cells, further studies are
      needed to develop strategies to enhance the ability of HAE cells to produce DA as
      well as the graft survival.

PMID- 10964483
TI  - Tumor necrosis factor-alpha-induced apoptosis in olfactory epithelium in vitro:
      possible roles of caspase 1 (ICE), caspase 2 (ICH-1), and caspase 3 (CPP32).
AB  - We investigated the potential roles of three members of the interleukin-1beta
      converting enzyme (ICE) protease family (caspases) in apoptosis in olfactory
      epithelium. By RT-PCR analysis, the mRNAs of caspase 1 (ICE), caspase 2 (ICH-1),
      and caspase 3 (CPP32) were detected in olfactory mucosa obtained from normal
      adults, E19 fetuses, and unilaterally bulbectomized rats. The transcript of
      caspase 2 disappeared in bulbectomized animals 3 and 5 days postoperatively, but
      reappeared 21 days postoperatively. This suggests that most of the caspase 2
      transcript was in olfactory sensory neurons. We used TNF-alpha to induce cell
      death in organotypic cultures of E19 olfactory epithelium and assayed the ability
      of three caspase inhibitors to reverse the TNF-alpha effect. After 6 h of
      treatment with medium containing TNF-alpha, a 2.5-fold increase in apoptotic body
      number was observed throughout the olfactory epithelium. Pretreatment of the
      cultures with either of two irreversible caspase inhibitors (Z-VAD-fmk, Ac-YVAD
      cmk) for 4 h, followed by a 6-h treatment with TNF-alpha plus an inhibitor,
      blocked TNF-alpha-induced cell death completely. Pretreatment with a third
      caspase inhibitor (Z-DEVD-fmk) in the same treatment schedule reduced the numbers
      of apoptotic cells significantly but not to the same extent as Z-VAD-fmk or Ac
      YVAD-cmk. Increasing the dose of any of the inhibitors reduced the numbers of
      apoptotic figures below those of control cultures, indicating that the inhibitory
      response is dose dependent. Taken together, the results suggest that caspases 1,
      2, and 3, and perhaps others that are blocked by the inhibitors we used,
      participate in TNF-alpha-induced cell death in vitro.

PMID- 10964485
TI  - Long-term expression driven by herpes simplex virus type-1 amplicons may fail due
      to eventual degradation or extrusion of introduced transgenes.
AB  - In gene therapy applications employing herpes simplex virus amplicon-based
      vectors, a prevailing problem is the down-regulation of transgene expression over
      time. We have applied a combined immunocytochemistry and fluorescent in situ
      hybridization method to determine whether down-regulation of transgene expression
      at the single-cell level correlates with loss of vector DNA from the host cell
      nucleus. Utilizing separate fluorescent labels (i.e., rhodamine, fluorescein, and
      4',6'-diamidino-2-phenlindole), we were able to simultaneously detect transgenes,
      their products, and their locations relative to the nuclear compartment of a
      single cell. Detection of the reporter gene lacZ and its encoded protein beta
      galactosidase (beta-gal) was accomplished in in vivo experiments of the dentate
      gyrus of rats. A time course study of the expression of the transgene post
      stereotactic microinfusion up to 60 days was made. Expression reached maximal
      levels within 12-24 h after infection, and lacZ presence was reduced to less than
      3% of its maximal levels within 36 h after infection. In comparing days 1 and 60
      post-stereotactic microinfusion, only one-fifth of the original DNA was observed
      in the area of a 100-mm radius around the site of microinfusion at day 60.
      Moreover, by comparing the locations of the reporter gene in cells that expressed
      the encoded protein versus those that did not, we found that introduced
      transgenes were preferentially localized in the nuclear periphery of down
      regulated host cells, compared to expressing host cells. These results suggest
      that nuclear compartmentalization may play a role in the down-regulation of our
      reporter gene by means of peripheralization, extrusion, and/or degradation.

PMID- 10964486
TI  - Neurons generated from adult rat hippocampal stem cells form functional
      glutamatergic and GABAergic synapses in vitro.
AB  - Basic fibroblast growth factor-responsive neural stem cells (NSCs) derived from
      adult rat hippocampus were earlier demonstrated to generate neurons and glia.
      These stem-cell-derived neurons express GABA, acetylcholinesterase, tyrosine
      hydroxylase, or calbindin. It has not been clear, however, whether or not these
      stem-cell-derived neurons are able to form functional synapses. In the present
      study, we investigated the development of synapse formation by adult hippocampus
      derived neural stem cells. NSCs from adult rat hippocampi and primary embryonic
      rat hippocampal neurons were cocultured on a glial feeder layer.
      Immunofluorescence studies revealed that some of the NSCs became immunoreactive
      for microtubule-associated protein 2ab, neurofilament 200, synaptobrevin, or
      synaptophysin. These cells possessed properties of functional neurons such as
      action potentials and miniature postsynaptic currents (mPSCs). The elicited mPSCs
      with rapid kinetics were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), but
      not by bicuculline (excitatory mPSCs). The remaining mPSCs had slower kinetics
      and were blocked by bicuculline, but not by DNQX (inhibitory mPSCs). We
      considered that the neurons derived from the adult NSCs expressed both non-NMDA
      glutamate receptors and the GABA(A) receptors and formed functional synapses. Our
      results demonstrate that adult NSCs can differentiate into neurons with
      functional glutamatergic and GABAergic synaptic transmission in vitro and support
      the concept that such neurons could integrate into the neuronal circuitry.

PMID- 10964484
TI  - Effects of age on gene expression during estrogen-induced synaptic sprouting in
      the female rat.
AB  - Age and estrogen treatment influenced fiber outgrowth and compensatory neuronal
      sprouting after unilateral entorhinal cortex lesions (ECL) which model Alzheimer
      disease-like deafferentation in the dentate gyrus of the hippocampus. In young
      F344 rats (3 months old), ovariectomy (OVX) decreased reactive fiber outgrowth by
      60%. Sprouting in middle-aged rats (18 months old) was reduced in intact females;
      no further reduction was caused by OVX. Several astrocyte mRNAs were measured in
      the dentate gyrus of young and middle-aged female rats in three different
      estrogen states (sham OVX, OVX, or OVX + estradiol) 1 week after ECL. Glial
      fibrillary acidic protein (GFAP) mRNA was twofold greater in middle-aged rats
      than young, although both ages showed threefold increases in response to ECL. In
      prior studies GFAP was found to be decreased by estradiol treatment 3-4 days
      after ECL; in this study GFAP mRNA had returned to sham OVX levels in young rats
      by 7 days post-ECL. Surprisingly, estradiol treatment increased GFAP mRNA levels
      by 25% above OVX in middle-aged rats. Apolipoprotein E (apoE) mRNA was decreased
      20% by age in the dentate, although both age groups showed a 25% increase in apoE
      mRNA in response to ECL. Apolipoprotein J (apoJ) mRNA was increased 20% in the
      dentate gyrus of middle-aged rats, and both age groups responded to ECL with a
      65% increase in apoJ mRNA. The estrogen state did not alter levels of either
      apolipoprotein mRNA in the deafferented dentate. The data suggest that the
      estrogen-induced decrease of GFAP in response to lesions does not persist at 7
      days post-ECL during sprouting. Overall effects of age on the dentate gyrus
      include elevated GFAP mRNA and decreased apoE mRNA. The cortical wound site
      showed consistent enhancement of GFAP mRNA in both age groups by estradiol above
      sham OVX and greater responses in middle-aged rats.

PMID- 10964487
TI  - Neurofilament-rich intraneuronal inclusions exacerbate neurodegenerative sequelae
      of brain trauma in NFH/LacZ transgenic mice.
AB  - Several neurodegenerative disorders are characterized by filamentous inclusions
      in neurons that selectively degenerate. The role these inclusions play in neuron
      degeneration is unclear, but this issue can be investigated experimentally in
      relevant animal models. The NFH/LacZ transgenic (TG) mice overexpress the high
      molecular-weight neurofilament (NF) subunit (NFH) fused to beta-galactosidase,
      and these hybrid proteins aggregate into NF-rich, filamentous neuronal
      cytoplasmic inclusions (NCIs) that have been implicated in the progressive, age
      dependent degeneration in subsets of affected neurons. Thus, these TG mice
      recapitulate some of the key pathology of neurodegenerative disorders with
      intraneuronal inclusions. To determine if the NCIs compromise neuron survival
      following traumatic brain injury (TBI), 3- to 6-month old TG and wild-type (WT)
      mice were subjected to TBI or sham injury. At 2 weeks post-TBI, the TG group
      showed increased TUNEL staining and activated caspase-3 immunoreactivity in cells
      of cerebral cortex, adjacent white matter, and hippocampus underlying the injury
      site, relative to control mice, but this labeling decreased at 4 weeks and was
      minimal thereafter. Compared to control mice, by 8 weeks postinjury, the TG mice
      showed a marked decrease in neuron density and increased gliosis in the
      hippocampal dentate gyrus and CA3 region as well as in the lateral thalamus,
      while the few remaining CA3 neurons exhibited cytoskeletal alterations, decreased
      synaptic protein immunoreactivity, and dissolution of NCIs. The more profound
      long-term neurodegenerative sequelae of TBI in the NFH/LacZ mice compared to WT
      mice suggest that the presence of intraneuronal inclusions may impair the
      recovery and long-term viability of injured neurons.

PMID- 10964489
TI  - Projections of the parabrachial nucleus in the old world monkey.
AB  - The efferent projections of the pontine parabrachial nucleus (PBN) were examined
      in the Old World monkey (Macaca fascicularis) using tritiated amino acid
      autoradiography and horseradish peroxidase histochemistry. Parabrachiofugal
      fibers ascended to the forebrain along three pathways: the central tegmental
      tract, the ventral ascending catecholaminergic pathway, and a pathway located on
      the midline between the medial longitudinal fasciculi. The PBN projected heavily
      to the central nucleus of the amygdala and the lateral division of the bed
      nucleus of the stria terminalis and moderately to the ventral tegmental area and
      the substantia nigra. Light terminal label also was present within the
      dorsomedial, ventromedial, lateral, supramammillary, and infundibular nuclei of
      the hypothalamus and the annular nucleus and the dorsal raphe nucleus within the
      brain stem. The overall pattern of terminal label was similar to that previously
      reported for nonprimate species, but several differences were notable. In monkey
      the projection to the ventrobasal thalamus did not coincide with the region that
      contains gustatory-responsive neurons. In rats, these parabrachiothalamic fibers
      convey gustatory activity but in the monkey these fibers may carry visceral
      afferent information. The projections from the PBN to the hypothalamus in the
      monkey were neither as widespread nor as intense as in the rat, and the monkey
      lacks a projection from the PBN to the frontal and insular cortices.

PMID- 10964490
TI  - Developmental regulation of BDNF and NT-3 expression by quinolinic acid in the
      striatum and its main connections.
AB  - Interactions between neurotrophic factors and neurotransmitters participate in
      the formation and maintenance of appropriate connections, as well as in
      neurodegenerative processes. Here we have measured changes in the developmental
      expression pattern of BDNF and NT-3 in the striatum, cortex, and substantia nigra
      induced by intrastriatal injection of the N-methyl-d-aspartate glutamate receptor
      agonist quinolinic acid (QUIN). Animals were injected at different postnatal
      ages, and BDNF and NT-3 mRNA levels were determined 6 h after lesion using a
      ribonuclease protection assay. Our results show a biphasic increase in BDNF mRNA
      levels in striatum and in the ipsilateral cortex at postnatal day (P)5 and P21.
      In contrast, although NT-3 expression did not change in the striatum, it was down
      regulated in the ipsilateral cortex at P5 and P30. Intrastriatal QUIN injection
      did not induce changes in either BDNF or NT-3 expression in the ipsilateral
      substantia nigra. These findings show that neurotrophin expression is
      developmentally regulated after excitotoxic injury, which suggests that this
      endogenous response may be involved in different neuronal maturation and
      vulnerability during development.

PMID- 10964488
TI  - Expression of a novel neuropeptide Y receptor subtype involved in food intake: an
      in situ hybridization study of Y5 mRNA distribution in rat brain.
AB  - Our group has reported on the cloning of a novel rat neuropeptide Y (NPY)
      receptor involved in NPY-induced food intake, the Y5 receptor. The distribution
      in rat brain of the mRNA encoding this receptor has been determined by in situ
      hybridization histochemistry, using radiolabeled oligonucleotide probes. Control
      experiments were carried out in cell lines transfected with either rat Y1 or rat
      Y5 cDNAs. With the exception of the cerebellum, only the antisense probes yielded
      hybridization signal in rat brain tissue sections. A number of brain regions
      contained hybridization signals indicative of Y5 mRNA localization. Chief among
      these were various hypothalamic nuclei, including the medial preoptic nucleus,
      the supraoptic nucleus, the paraventricular nucleus, and the lateral
      hypothalamus. Other regions with substantial hybridization signals included the
      midline thalamus, parts of the amygdala and hippocampus, and some midbrain and
      brain-stem nuclei. In general a low density of Y5 mRNA was observed in most
      cortical structures, with the exception of the cingulate and retrosplenial
      cortices, each of which contained a moderate abundance of Y5 hybridization
      signal. The distribution of this receptor mRNA is consistent with a role for the
      Y5 receptor in food intake and also suggests involvement in other processes
      mediated by NPY.

PMID- 10964492
TI  - Antiparkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of
      Parkinson's disease.
AB  - Dopamine-replacement strategies form the basis of most symptomatic treatments for
      Parkinson's disease. However, since long-term dopamine-replacement therapies are
      characterized by many side effects, most notably dyskinesia, the concept of a
      nondopaminergic therapy for Parkinson's disease has attracted great interest. To
      date, it has proved difficult to devise a nondopaminergic therapy with efficacy
      comparable to that of dopamine replacement. In animal models of Parkinson's
      disease, loss of striatal dopamine leads to enhanced excitation of striatal NR2B
      containing NMDA receptors. This is responsible, in part at least, for generating
      parkinsonian symptoms. Here we demonstrate that, in the MPTP-lesioned marmoset,
      monotherapy with the NR2B-selective NMDA receptor antagonist, ifenprodil,
      administered de novo, has antiparkinsonian effects equivalent to those of l-DOPA
      (administered as its methyl ester form). In MPTP-lesioned marmosets, median
      mobility scores, following vehicle-treatment were 12.5/h (range 6-21), compared
      to 61/h (range 26-121) in normal, non-MPTP-lesioned animals. Following ifenprodil
      (10 mg/kg) treatment in MPTP-lesioned marmosets, the median mobility score was
      66/h (range 34-93), and following l-DOPA (10 mg/kg i.p.) treatment 89/h (range 82
      92). The data support the proposal that NR2B-selective NMDA receptor antagonists
      have potential as a nondopaminergic monotherapy for the treatment of parkinsonian
      symptoms when given de novo.

PMID- 10964491
TI  - Neurotrophins require distinct extracellular signals to promote the survival of
      CNS neurons in vitro.
AB  - Althoughthe neurotrophins BDNF and NT-3 have been recognized as potent survival
      factors for distinct neuronal populations in the peripheral nervous system, they
      seem to have only minor effects on the survival of CNS neurons. In the present
      study, we provide evidence that BDNF and NT-3 require distinct additional
      extracellular signals in order to effectively promote the survival of several
      established populations of target neurons in the CNS. In dissociated cell
      cultures of the embryonic rat mesencephalon, BDNF promoted dopaminergic cell
      survival only after a delay of several days. Even after prolonged cultivation,
      survival promoting effects were completely absent with NT-3. Irrespective of the
      cultivation time, survival promoting effects of both BDNF and NT-3 on
      dopaminergic neurons were induced or potentiated upon simultaneous depolarization
      of cultured mesencephalic cells with NMDA or upon activation of cAMP/PKA
      dependent signaling pathways with dibutyryl cAMP. Dibutyryl cAMP (dbcAMP), but
      not NMDA, also potentiated or induced the survival promoting effects of BDNF and
      NT-3 on cultured cerebellar granule cells. None of these substances, either alone
      or in combination, affected the survival of cultured cortical neurons. However,
      cortical cell survival increased upon depolarization with elevated potassium; an
      effect known to involve the induction of an autocrine BDNF loop. In both
      cerebellar and mesencephalic neurons, but not in cortical neurons, dbcAMP also
      potentiated neurotrophin-induced c-fos response, indicating intimate cross
      coupling of signaling pathways activated by these different factors. Together
      these findings suggest that in the CNS, neurotrophins preferentially promote the
      survival of functionally active neurons. Our findings further reveal that the
      neuronal response to neurotrophins is modulated in a brain region-specific
      manner.

PMID- 10964493
TI  - Overexpression of GAP-43 in thalamic projection neurons of transgenic mice does
      not enable them to regenerate axons through peripheral nerve grafts.
AB  - It is well established that some populations of neurons of the adult rat central
      nervous system (CNS) will regenerate axons into a peripheral nerve implant, but
      others, including most thalamocortical projection neurons, will not. The ability
      to regenerate axons may depend on whether neurons can express growth-related
      genes such as GAP-43, whose expression correlates with axon growth during
      development and with competence to regenerate. Thalamic projection neurons which
      fail to regenerate into a graft also fail to upregulate GAP-43. We have tested
      the hypothesis that the absence of strong GAP-43 expression by the thalamic
      projection neurons prevents them from regenerating their axons, using transgenic
      mice which overexpress GAP-43. Transgene expression was mapped by in situ
      hybridization with a digoxigenin-labeled RNA probe and by immunohistochemistry
      with a monoclonal antibody against the GAP-43 protein produced by the transgene.
      Many CNS neurons were found to express the mRNA and protein, including neurons of
      the mediodorsal and ventromedial thalamic nuclei, which rarely regenerate axons
      into peripheral nerve grafts. Grafts were implanted into the region of these
      nuclei in the brains of transgenic animals. Although these neurons strongly
      expressed the transgene mRNA and protein and transported the protein to their
      axon terminals, they did not regenerate axons into the graft, suggesting that
      lack of GAP-43 expression is not the only factor preventing thalamocortical
      neurons regenerating their axons.

PMID- 10964494
TI  - Cyclosporin A enhances survival, ameliorates brain damage, and prevents secondary
      mitochondrial dysfunction after a 30-minute period of transient cerebral
      ischemia.
AB  - Cyclosporin A (CsA) has been shown to be efficacious in protecting against
      ischemic injury after short periods (5 to 10 min) of forebrain ischemia. The
      present experiments were undertaken to study if a long period of forebrain
      ischemia (30 min), induced at a brain temperature of 37 degrees C, is compatible
      with survival and if the brain damage incurred can be ameliorated by CsA. The
      results showed that animals subjected to 30 min of forebrain ischemia at a brain
      temperature of 37 degrees C failed to survive after the first 24 h of recovery
      and showed extensive neuronal necrosis in all selectively vulnerable regions
      after 1 day of survival. CsA, when injected in combination with an intracerebral
      lesion to open the blood-brain barrier, markedly prolonged the survival time. CsA
      injected animals also showed amelioration of histological lesions, an effect that
      was sustained for at least 4 days. Experiments with mitochondria isolated from
      the neocortex and hippocampus showed that state 3 respiratory rates decreased
      during ischemia, recovered after 1 and 3 h of recirculation, and then showed a
      secondary decline at 6 h. Administration of CsA prevented this secondary decline.
      Measurements of neocortical cerebral blood flow showed that there was no
      secondary hypoperfusion prior to secondary mitochondrial dysfunction, implying
      that changes in blood flow may not be responsible for the rapidly developing,
      secondary brain damage. The results thus demonstrate that if brain temperature is
      upheld at 37 degrees C, a 30-min period of ischemia is not compatible with
      survival after the first day of recovery, and gross histopathological damage
      develops within that period. CsA was efficacious in prolonging animal survival,
      ameliorating brain damage, and preventing the secondary mitochondrial
      dysfunction. Since CsA blocks the mitochondrial permeability transition pore its
      action may, at least in part, be on mitochondrial integrity and function.

PMID- 10964495
TI  - MPP(+) increases the vulnerability to oxidative stress rather than directly
      mediating oxidative damage in human neuroblastoma cells.
AB  - MPP(+), an active metabolite of MPTP, causes a dopaminergic neuronal degeneration
      similar to that observed in Parkinson's disease. Current data suggest that MPP(+)
      induced cytotoxicity may be mediated by oxygen free radicals. To evaluate this
      hypothesis, we first investigated whether MPP(+) could cause oxidative stress by
      producing oxygen free radicals in the SH-SY5Y, human neuroblastoma cell line.
      MPP(+) was toxic to the cells dose-dependently but did not increase the level of
      lipid peroxidation at toxic concentrations. Second, we examined the effects of
      various antioxidants and an inhibitor of nitric oxide synthase (NOS) on the
      development of MPP(+) cytotoxicity. Pretreatment with antioxidants such as
      ascorbic acid, Trolox, phenyl-tertiary-butyl-nitrone (PBN), which show protective
      effects on tert-butyl hydroperoxide (tBOOH) toxicity did not attenuate MPP(+)
      cytotoxicity. Similarly, the combination of antioxidant enzymes, SOD and catalase
      (50 U/ml, respectively), did not protect the cells from the toxic action of
      MPP(+). Also N-nitro-l-arginine methyl ester (NAME), a competitive inhibitor of
      NOS, and combined incubation with NAME and antioxidant enzymes failed to
      attenuate MPP(+) cytotoxicity. On the other hand, a sublethal dose of MPP(+)
      potentiated iron and H(2)O(2)-induced cytotoxicity. These results suggest that
      oxygen free radicals may not be a primary cause of MPP(+)-induced cell death but
      that MPP(+) increases the vulnerability of cells to oxidative stress.

PMID- 10964496
TI  - Influence of environment on the efficacy of intrastriatal dopaminergic grafts.
AB  - Functional recovery is influenced by experience. The aim of the present work was
      to examine the effects of "enriched" environment (EE) versus an "impoverished"
      environment on the anatomical and functional integration of intrastriatal
      dopaminergic grafts. These influences were studied using a paradigm where
      grafting was performed before the dopamine-depleting lesion. Dopaminergic grafts
      were implanted into the left neostriatum of adult male rats. In the enriched
      group, grafted rats were housed collectively and were trained on different
      behavioral tests following grafting. In contrast, impoverished grafted rats were
      housed individually and not further manipulated. Ten weeks after grafting, the
      mesotelencephalic dopaminergic pathway was destroyed unilaterally to the grafted
      side and different behaviors were followed for 7 months. Grafting prior to
      lesioning had no prophylactic effects on the performance as the graft did not
      prevent the onset of the lesion-induced impairments. However, under EE
      conditions, a graft effect was manifested in the reduction of drug-induced
      rotation and on the indices of bias as tested by a spatial alternation test. No
      positive graft effects were observed in the skilled paw reaching test. Grafted
      rats raised under impoverished conditions performed in a fashion
      indistinguishable from the control lesioned animals on most measures of behavior.
      A beneficial effect of EE conditions was observed on survival of TH-positive
      neurons within the grafts. The results suggest that survival of grafted neurons,
      and the reduction of the magnitude of particular behavioral impairments, can be
      optimized by increasing the complexity of the subject's environment.

PMID- 10964497
TI  - Absence of p53: no effect in a transgenic mouse model of familial amyotrophic
      lateral sclerosis.
AB  - Familial amyotrophic lateral sclerosis (ALS) has been linked in some families to
      dominantly inherited mutations in the gene encoding copper-zinc superoxide
      dismutase 1 (Cu-Zn SOD1). Transgenic mice expressing a mutant human Cu-Zn SOD1
      (G93A) develop a dominantly inherited adult-onset paralytic disorder that
      replicates many of the clinical and pathological features of familial ALS.
      Increased p53 immunoreactivity has been reported in the motor cortex and spinal
      ventral horns of postmortem tissue from ALS patients. The nuclear phosphoprotein
      p53 is an important regulator of cellular proliferation, and increasing evidence
      supports the role of p53 in regulating cellular apoptosis. To assess the role of
      p53-mediated apoptosis in amyotrophic lateral sclerosis, mice deficient in both
      p53 alleles (p53-/-) were crossed with transgenic mice expressing the G93A mutant
      (G93A+), creating novel transgenic knockout mice. The animals (p53 +/+G93A+,
      p53+/-G93A+, p53-/-G93A+) were examined at regular intervals for cage activity,
      upper and lower extremity strength, and mortality. At 120 days from birth mice
      from each genotype were sacrificed, and L2-L3 anterior horn motor neurons were
      counted. There was no significant difference in time to onset of behavioral
      decline, mortality, or motor neuron degeneration between the different genotypes.
      Despite evidence that p53 plays an important role after acute neuronal injury,
      the current study suggests that p53 is not significantly involved in cell death
      in the G93A+ transgenic mouse model of familial ALS.

PMID- 10964498
TI  - Alterations in rat striatal glutamate synapses following a lesion of the cortico-
      and/or nigrostriatal pathway.
AB  - Ultrastructural changes within the ipsilateral dorsolateral striatum were
      investigated 1 month following a unilateral ablation of the rat frontal cortex
      (CTX), removing corticostriatal input, or injection of the neurotoxin, 6
      hydroxydopamine (6-OHDA), into the substantia nigra pars compacta, removing
      nigrostriatal input. In addition, a combined ipsilateral cortical and 6-OHDA
      lesion (CTX/6-OHDA) was carried out. We find that following a CTX, 6-OHDA, or
      CTX/6-OHDA lesion, there was a significant decrease in the density of striatal
      nerve terminal glutamate immunoreactivity compared to the control group. There
      was also a significant increase in all three lesion groups in the mean percentage
      of asymmetrical synapses associated with a perforated postsynaptic density. There
      was a large increase within the CTX/6-OHDA-lesioned group and a smaller but still
      significant increase in the CTX-lesioned group in the percentage of terminals or
      boutons with multiple synaptic contacts (i.e., multiple synaptic boutons, MSBs),
      compared to either the 6-OHDA or the control group. There was no change in any of
      these measurements within the contralateral striatum. There was a significant
      decrease in the number of apomorphine-induced contralateral rotations in the
      CTX/6-OHDA versus the 6-OHDA-lesioned group. Animals receiving just the single
      CTX or 6-OHDA lesion recovered in motor function compared to the control group as
      measured by the Rotorod test, while the CTX/6-ODA-lesioned group recovered to
      less than 50% of the control level. The data suggest that following a CTX and/or
      6-OHDA lesion, there is an increase in striatal glutamatergic function. The large
      increase in the percentage of MSBs in the combined lesion group suggests that
      dopamine or other factors released by the dopamine terminals assist in regulating
      synapse formation.

PMID- 10964499
TI  - Syndecan-1 signals independently of beta1 integrins during Raji cell spreading.
AB  - Syndecan-1-expressing Raji lymphoid cells (Raji-S1 cells) bind and spread rapidly
      when attaching to matrix ligands that contain heparan sulfate-binding domains.
      However, these ligands also contain binding sites for integrins, which are widely
      known to signal, raising the question of whether the proteoglycan core protein
      participates in generation of the signal for spreading. To address this question,
      the spreading of the Raji-S1 cells is examined on ligands specific for either
      beta1 integrins, known to be present on the Raji cells, or the syndecan-1 core
      protein. The cells adhere and spread on invasin, a ligand that activates beta1
      integrins, the IIICS fragment of fibronectin, which is a specific ligand for the
      alpha4beta1 integrin, or mAb281.2, an antibody specific for the syndecan-1 core
      protein. The signaling resulting from adhesion to the syndecan-specific antibody
      appears integrin independent as (i) the morphology of the cells spreading on the
      antibody is distinct from spreading initiated by the integrins alone; (ii)
      spreading on the syndecan or integrin ligands is affected differently by the
      kinase inhibitors tyrphostin 25, genistein, and staurosporine; and (iii)
      spreading on the syndecan-specific antibody is not disrupted by blocking beta1
      integrin activation with mAb13, a beta1 inhibitory antibody. These data
      demonstrate that ligation of syndecan-1 initiates intracellular signaling and
      suggest that this signaling occurs when cells expressing syndecan-1 adhere to
      matrix ligands containing heparan sulfate-binding domains.

PMID- 10964500
TI  - Posttranslational modifications and beta/gamma chain associations of human
      laminin alpha1 and laminin alpha5 chains: purification of laminin-3 from
      placenta.
AB  - Laminins assemble into trimers composed of alpha, beta, and gamma chains which
      posttranslationally are glycosylated and sometimes proteolytically cleaved. In
      the current paper we set out to characterize posttranslational modifications and
      the laminin isoforms formed by laminin alpha1 and alpha5 chains. Comparative
      pulse-chase experiments and deglycosylation studies in JAR cells established that
      the M(r) 360,000 laminin alpha1 chain is glycosylated into a mature M(r) 400,000
      band while the M(r) 370,000 laminin alpha5 chain is glycosylated into a M(r)
      390,000 form that upon secretion is further processed into a M(r) 380,000 form.
      Hence, despite the shorter peptide length of alpha1 chain in comparison with the
      alpha5 chain, secreted alpha1 assumes a larger size in SDS-PAGE due to a higher
      degree of N-linked glycosylation and due to the lack of proteolytic processing.
      Immunoprecipitations and Western blotting of JAR laminins identified laminin
      alpha1 and laminin alpha5 chains in laminin-1 and laminin-10. In placenta laminin
      alpha1 chain (M(r) 400,000) and laminin alpha5 chain (M(r) 380, 000/370,000
      doublet) were found in laminin-1/-3 and laminin-10/-11. Immunohistochemically we
      could establish that the laminin alpha1 chain in placenta is deposited in the
      developing villous and trophoblast basement membrane, also found to contain
      laminin beta2 chains. Surprisingly, a fraction of the laminin alpha1 chain from
      JAR cells and placenta could not be precipitated by antibodies to laminin beta1
      beta3 chains, possibly pointing to an unexpected complexity in the chain
      composition of alpha1-containing laminin isoforms.

PMID- 10964501
TI  - Mass cultured human fibroblasts overexpressing hTERT encounter a growth crisis
      following an extended period of proliferation.
AB  - During the process of immortalization, at least two mortality checkpoints, M1 and
      M2, must be bypassed. Cells that have bypassed M1 (senescence) have an extended
      life span, but are not necessarily immortal. Recent studies have shown that
      ectopic expression of the catalytic subunit of telomerase (hTERT) enables normal
      human cells to bypass senescence (M1) and oncogene transformed cells to avert
      crisis (M2) and become immortal. However, it is unclear whether hTERT expression
      is sufficient for normal human fibroblasts to overcome both M1 and M2 and become
      immortal. We have investigated the role of telomerase in immortalization by
      maintaining mass cultures of hTERT-transduced primary human fetal lung
      fibroblasts (MRC-5 cells) for very long periods of time (more than 2 years). In
      the present studies, up to 70% of MRC-5 cells were transduced with retroviral
      vectors that express hTERT. hTERT-transduced cells exhibited high levels of
      telomerase activity, elongation of telomeres, and proliferation beyond
      senescence. However, after proliferating for more than 36 population doublings
      (PDLs) beyond senescence, the overall growth rate of hTERT-expressing cells
      declined. During theses periods of reduced growth, hTERT-transduced MRC-5 cells
      exhibited features typical of cells in crisis, including an increased rate of
      cell death and polyploidy. In some instances, very late passage cells acquired a
      senescence-like phenotype characterized by arrest in the G1 phase of the cell
      cycle and greatly reduced DNA synthesis. At the onset of crisis, hTERT-transduced
      cells expressed high levels of telomerase and had very long telomeres, ranging up
      to 30 kb. Not all cells succumbed to crisis and, consequently, some cultures have
      proliferated beyond 240 PDLs, while another culture appears to be permanently
      arrested at 160 PDLs. Late passage MRC-5 cells, including postcrisis cells,
      displayed no signs of malignant transformation. Our results are consistent with
      the model in which telomerase and telomere elongation greatly extends cellular
      life span without inducing malignant changes. However, these investigations also
      indicate that hTERT-expressing cells may undergo crisis following an extended
      life span and that immortality is not the universal outcome of hTERT expression
      in normal diploid fibroblasts.

PMID- 10964502
TI  - Reactive oxidizing species produced near the plasma membrane induce apoptosis in
      bovine aorta endothelial cells.
AB  - Many cytotoxic agents initiate apoptosis by generating reactive oxidizing species
      (ROS). The goal of this study was to determine whether apoptosis could be induced
      by initial reactions of ROS near the plasma membrane. Bovine aorta endothelial
      cells (BAEC) were illuminated with evanescent wave visible radiation, which has
      limited penetration into the basal surface of cells, or by trans-radiation.
      Imaging of fluorescent dyes localizing in the plasma membrane, mitochondria, or
      nucleus confirmed that evanescent wave radiation excited only dyes in and near
      the plasma membrane. Singlet oxygen, an ROS generated by photosensitization, has
      a very short lifetime, ensuring that it oxidizes molecules residing in or very
      close to the plasma membrane when evanescent wave radiation is used. Cells with
      condensed nuclei were considered apoptotic and were quantified after treatment
      with varying doses of light. Annexin V staining without propidium iodide staining
      confirmed that these cells were apoptotic. The doses required to induce apoptosis
      using evanescent wave radiation were 10-fold greater than those needed for trans
      irradiation. Quantitative analysis of the evanescent wave penetration into cells
      supports a mechanism in which the singlet oxygen created near the plasma
      membrane, rather than at intracellular sites, was responsible for initiation of
      apoptosis.

PMID- 10964503
TI  - The MHC class II-associated chicken invariant chain shares functional properties
      with its mammalian homologs.
AB  - The nucleotide sequence of chicken invariant chain (Ii) was determined, and the
      amino acid sequence similarity with human Ii is 61%. Certain regions important
      for the biological function of human Ii are highly conserved between chicken and
      mammals. The cytoplasmic tail of chicken Ii fused to the plasma membrane reporter
      molecule neuraminidase relocated the protein to endosomes. Moreover, like the
      mammalian orthologs, the cytoplasmic tail was found to contain two independent
      leucine-based endosomal sorting signals. Chicken Ii was found to interact with
      human Ii and crosslinking studies also indicate that chicken Ii assembles as a
      trimer. The chicken Ii can furthermore bind the human MHC class II (HLA-DR1).
      Many of the functional properties between the chicken Ii and its mammalian
      orthologs are thus maintained in spite of their sequence differences.

PMID- 10964504
TI  - NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2
      domain protein shb requires activation of the Rap1 pathway.
AB  - The Src homology 2 (SH2) domain adaptor protein Shb has been shown to transmit
      NGF- and FGF-2-dependent differentiation signals in PC12 cells. To study if this
      involves signaling through the small GTPase Rap1, Rap1 activity was assessed in
      Shb-overexpressing PC12 cells. We demonstrate that NGF and EGF induce Rap1
      activation in PC12-Shb cells, while FGF-2 fails to do so. However, PC12 cells
      expressing Shb with an inactivated SH2 domain do not respond to NGF stimulation
      with Rap1 activation. The CrkII SH2 domain interacts with Shb and a 130- to 135
      kDa phosphotyrosine protein present mainly in PC12-Shb cells and these
      interactions may thus relate to the effect of Shb on Rap1 activation. Transient
      expression of RalGDS-RBD or Rap1GAP to block the Rap1 pathway reduces the NGF
      dependent neurite outgrowth in PC12-Shb cells. These results suggest a role of
      Shb in NGF-dependent Rap1 signaling and this pathway may be of significance for
      neurite outgrowth under certain conditions.

PMID- 10964505
TI  - Modulation of extracellular matrix adhesiveness by neurocan and identification of
      its molecular basis.
AB  - Neurocan is one of the major chondroitin sulfate proteoglycans of perinatal
      rodent brain. HEK-293 cells producing neurocan recombinantly show changes in
      their behavior. The expression of full-length neurocan led to a detachment of the
      secreting cells and the formation of floating spheroids. This occurred in the
      continuous presence of 10% fetal bovine serum in the culture medium. Cells
      secreting fragments of neurocan-containing chondroitin sulfate chains and the C
      terminal domain of the molecule showed a similar behavior, whereas cells
      expressing fragments of neurocan-containing chondroitin sulfate chains but
      lacking parts of the C-terminal domain did not show spheroid formation. Cells
      secreting the hyaluronan-binding N-terminal domain of neurocan showed an enhanced
      adhesiveness. When untransfected HEK-293 cells were plated on a surface
      conditioned by spheroid-forming cells, they also formed spheroids. This effect
      could be abolished by chondroitinase treatment of the conditioned surface. The
      observations indicate that the ability of the chondroitin sulfate proteoglycan
      neurocan to modulate the adhesive character of extracellular matrices is
      dependent on the structural integrity of the C-terminal domain of the core
      protein.

PMID- 10964506
TI  - Involvement of protein kinase C-regulated ceramide generation in inostamycin
      induced apoptosis.
AB  - Activation of caspases is commonly involved in the apoptosis induced by various
      anticancer drugs. However, the upstream events leading to the activation of
      caspases seem to be specific to each anticancer drug. In the present study, we
      examined the possible involvement of protein kinase C (PKC) and ceramide
      generation in caspase-3(-like) protease activation induced by inostamycin, a
      phosphatidylinositol synthesis inhibitor. Treatment of cells with 12-O
      tetradecanoyl phorbol-13-acetate (TPA), an activator of PKC, suppressed the
      release of cytochrome c from mitochondria and the activation of caspase-3(-like)
      proteases in inostamycin-treated cells, but not in other anticancer drug-treated
      cells. Inostamycin induced the elevation of intracellular ceramide levels, and
      fumonisin B1, an inhibitor of ceramide synthase, inhibited inostamycin-induced
      cytochrome c release, caspase-3(-like) protease activation, and apoptosis.
      Moreover, TPA also inhibited inostamycin-induced ceramide synthesis. Taken
      together, our results suggest that inostamycin-induced apoptosis is mediated by
      PKC-regulated ceramide generation, leading to the activation of a caspase
      cascade.

PMID- 10964507
TI  - Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import
      of the viral preintegration complex.
AB  - Heat-shock proteins (Hsp's) are a family of molecular chaperones that contribute
      to protection from environmental stress. In this report, we demonstrate that a
      member of this family, Hsp70, facilitates nuclear import of HIV-1 preintegration
      complexes (PICs). The mechanism of this activity appears to be similar to the one
      used by Vpr, an HIV-1 protein regulating viral nuclear import and replication in
      macrophages. Indeed Hsp70 stimulated binding of HIV-1 matrix antigen to GST
      karyopherin alpha fusion protein and rescued nuclear import of a Vpr-defective
      HIV-1 strain in vitro. Binding studies with truncated forms of GST-karyopherin
      alpha demonstrated that both Vpr and Hsp70 bind to a region in the amino-terminal
      part of the karyopherin alpha molecule. This region appears to be distinct from
      the binding sites for two other karyopherin alpha cargoes, basic-type NLS
      containing proteins and transcription factor STAT-1. Vpr competed with Hsp70 for
      binding to karyopherin alpha. These results suggest the presence of a novel
      regulatory site on karyopherin alpha which is used by Hsp70 and Vpr to stimulate
      interaction between the HIV-1 PIC and karyopherin alpha and thus promote viral
      nuclear import.

PMID- 10964508
TI  - Instability of interstitial telomeric sequences in the human genome.
AB  - The length variability of four human interstitial telomeric sequences (ITs) is
      described. Three of the ITs contain short telomeric stretches ranging between 53
      and 84 bp and are localized in 21q22, 2q31, and 7q36; the fourth IT derives from
      the subtelomeric domain of chromosome 6p and contains a tract of a few hundred
      basepairs of exact and degenerate repeats. Using primers flanking the repeats, we
      amplified the genomic DNA from unrelated individuals and from family members, and
      we found that all the loci are polymorphic. At the 21q22 IT locus, two equally
      frequent alleles were found, while the number of alleles at the 2q31, 7q36, and
      6pter IT loci was 8, 6, and 4, respectively. Sequence analysis revealed that in
      the three loci containing short ITs the alleles differ from one another for
      multiples of the hexanucleotide; it is likely that the mechanism leading to the
      polymorphism is DNA polymerase slippage. These loci were also unstable in gastric
      tumor cells characterized by microsatellite instability. At the 6pter IT locus,
      the four alleles range in length from about 500 to about 700 bp; this variability
      is probably due to unequal exchange or gene conversion. Our data indicate that
      stretches of exact internal telomeric repeats can be highly unstable, like
      microsatellites with shorter units, and that they can be useful polymorphic
      markers for linkage analysis, for forensic applications, and for the detection of
      genetic instability in tumors.

PMID- 10964509
TI  - Modular bacterial artificial chromosome vectors for transfer of large inserts
      into mammalian cells.
AB  - To facilitate the use of large-insert bacterial clones for functional analysis,
      we have constructed new bacterial artificial chromosome vectors, pPAC4 and
      pBACe4. These vectors contain two genetic elements that enable stable maintenance
      of the clones in mammalian cells: (1) The Epstein-Barr virus replicon, oriP, is
      included to ensure stable episomal propagation of the large insert clones upon
      transfection into mammalian cells. (2) The blasticidin deaminase gene is placed
      in a eukaryotic expression cassette to enable selection for the desired mammalian
      clones by using the nucleoside antibiotic blasticidin. Sequences important to
      select for loxP-specific genome targeting in mammalian chromosomes are also
      present. In addition, we demonstrate that the attTn7 sequence present on the
      vectors permits specific addition of selected features to the library clones.
      Unique sites have also been included in the vector to enable linearization of the
      large-insert clones, e. g., for optical mapping studies. The pPAC4 vector has
      been used to generate libraries from the human, mouse, and rat genomes. We
      believe that clones from these libraries would serve as an important reagent in
      functional experiments, including the identification or validation of candidate
      disease genes, by transferring a particular clone containing the relevant
      wildtype gene into mutant cells or transgenic or knock-out animals.

PMID- 10964511
TI  - Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript
      profiling analysis.
AB  - Among the high-throughput, comprehensive technological methods used to analyze
      transcript expression levels, array-based hybridization and serial analysis of
      gene expression (SAGE) are currently the most common approaches. To compare the
      quantitative accuracy of oligonucleotide array and SAGE, both methods were
      carried out on identical RNA specimens prepared from human blood monocytes and
      granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced macrophages.
      For SAGE analysis, 57,560 and 57,463 tags were obtained from monocytes and
      macrophages, respectively, resulting in approximately 28,000 different tags,
      while oligo array hybridization was performed with GeneChip (Affymetrix), which
      represents approximately 6000 transcripts. These two methods correlated quite
      well in both absolute expression analyses and comparative analyses during
      differentiation. The correlation was better for genes with higher expression
      levels and greater changes in expression. This finding suggests that GeneChip
      technology is reasonably reliable for quantitative analysis of expression
      profiling and would be appropriate as a common platform upon which to build a
      gene expression database.

PMID- 10964510
TI  - Molecular cloning of the critical region for glomerulopathy with fibronectin
      deposits (GFND) and evaluation of candidate genes.
AB  - Glomerulopathy with fibronectin deposits (GFND, MIM 601894) is an autosomal
      dominant kidney disease that leads to terminal renal failure at a median age of
      47 years. It represents a distinct entity of membranoproliferative
      glomerulonephritis (MPGN) type III and is characterized by the unique feature of
      massive glomerular deposits of fibronectin. We have recently localized a gene
      locus for GFND to human chromosome 1q32 by total genome linkage analysis in a
      large kindred, within a 4.1-cM critical interval between markers D1S2872 and
      D1S2891. This interval contains a cluster of genes for "regulators of complement
      activation" (RCA), which represent strong candidates for GFND. To identify
      positional candidate genes for GFND within the critical genetic interval, we here
      report the cloning of the entire critical GFND region in a complete YAC and
      partial PAC contig. We constructed a high-resolution transcriptional map, thereby
      defining positional and functional candidate genes for the disease. To evaluate
      their role in GFND, we performed functional studies on RCA proteins in GFND
      patients from the large kindred, as well as mutational analysis of the genes for
      complement receptor-2 (CR2), membrane cofactor protein (MCP), and decay
      accelerating factor (DAF). Although no loss-of-function mutation has been
      identified as yet, these data provide a basis for the examination of candidate
      genes for GFND and other genes for MPGN, which localize to the vicinity of the
      GFND region.

PMID- 10964513
TI  - Gene structure, chromosomal localization, and expression pattern of Capn12, a new
      member of the calpain large subunit gene family.
AB  - We report the identification of mouse Capn12, a new member of the calpain large
      subunit gene family. It possesses potential protease and calcium-binding domains,
      features typical of the classical calpains. In situ hybridization and Northern
      blot analysis demonstrate that during the anagen phase of the hair cycle the
      cortex of the hair follicle is the major expression site of Capn12. The gene was
      sequenced in its entirety and consists of 21 exons spanning 13 kb with an exon
      intron structure typical of the calpain gene family. The last exon of the mouse
      Actn4 gene overlaps the 3' end of Capn12 but in the opposite orientation. This
      overlap between the two genes is conserved in the human genome. Three versions of
      the Capn12 mRNA transcript were identified. They occur as a result of alternative
      splicing, and two of these encode a protein lacking the C-terminal calmodulin
      like domain. Radiation hybrid mapping localized Capn12 to mouse chromosome 7,
      closely linked to a marker positioned at 10.4 cM. Refined mapping of Capn5, also
      previously localized to chromosome 7, indicated that it was not closely linked to
      Capn12, mapping tightly linked to a marker positioned at 48.5 cM.

PMID- 10964512
TI  - Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene,
      tertiary structural modeling of the human SCOT monomer, and characterization of
      three pathogenic mutations.
AB  - The activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT;
      EC 2.8.3.5) is the main determinant of the ketolytic capacity of tissues.
      Hereditary SCOT deficiency causes episodic ketoacidosis. Here we describe the
      human SCOT gene, which spans more than 100 kb and contains 17 exons, on
      chromosome 5p13. We report pathogenic missense mutations in three SCOT-deficient
      patients designated GS04, 05, and 06. GS04 is a G219E/G324E compound; GS05 is a
      V221M homozygote, and GS06 is a G324E homozygote. We constructed a tertiary
      structural model of human SCOT by homology modeling based on the known structure
      of Acidaminococcus fermentans glutaconate CoA transferase. The model predicts
      that V221 and G219 are on the dimerizing surface, whereas G324 is near the active
      site. SCOT activity was reduced to a comparable degree in all three patients, but
      in a transient expression assay in SCOT-deficient fibroblasts, cDNAs containing
      G219E and G324E produced no detectable activity, whereas V221M constructs yielded
      approximately 10% of the control peptide level and detectable specific activity.
      Interestingly, GS05 had the mildest clinical course reported to date and
      detectable levels of SCOT protein in fibroblasts.

PMID- 10964514
TI  - A novel human cytochrome P450 4F isoform (CYP4F11): cDNA cloning, expression, and
      genomic structural characterization.
AB  - By a combination of cDNA library screening and rapid amplification of cDNA ends
      analysis, a novel human cytochrome P450 4F isoform has been cloned and sequenced.
      The new 4F isoform is designated CYP4F11 and contains 1765 nucleotides. The
      coding region encodes 524 amino acid residues, and the heme-binding region is
      highly conserved. The CYP4F11 amino acid sequence has 80.0, 82.3, and 79.2%
      identity to CYP4F2, CYP4F3, and CYP4F8 amino acid sequences, respectively. In
      vitro translation shows the molecular mass of CYP4F11 is approximately 57 kDa,
      consistent with the calculated molecular mass. CYP4F11 is expressed mainly in
      human liver, followed by kidney, heart, and skeletal muscle. The genomic
      structure of CYP4F11 was solved by database searching and computer analysis. The
      coding region of CYP4F11 has 12 exons. The CYP4F11 gene is located 16 kb upstream
      of the CYP4F2 gene on chromosome 19. This is consistent with the notion that the
      human cytochrome P450 4F genes form a cluster on chromosome 19.

PMID- 10964515
TI  - Isolation, characterization and targeted disruption of mouse ppia: cyclophilin A
      is not essential for mammalian cell viability.
AB  - Cyclophilins (CyPs) are a family of proteins found in organisms ranging from
      prokaryotes to humans. These molecules exhibit peptidyl-prolyl isomerase activity
      in vitro, suggesting that they influence the conformation of proteins in cells.
      CyPs also bind with varying affinities to the immunosuppressive drug cyclosporin
      A (CsA), a compound used clinically to prevent allograft rejection. The founding
      member of the family, cyclophilin A (CyPA), is an abundant, ubiquitously
      expressed protein of unknown function that binds with nanomolar affinity to CsA.
      Here, we describe the isolation and characterization of mouse Ppia (mPpia), the
      gene encoding CyPA. Ppia was isolated using a PCR screen that distinguishes the
      expressed gene from multiple pseudogenes present in the mouse genome. mPpia
      consists of 5 exons and 4 introns spanning roughly 4.5 kb and maps to chromosome
      11 near the centromere. Sequence analysis of a 369-bp fragment from the proximal
      promoter region of mPpia revealed the presence of a TATA box and sites recognized
      by several transcriptional regulators, including Sp1, AP-2, GATA factors, c-Myb,
      and NF-IL-6. This region is sufficient to drive high-level reporter gene
      expression in transfected cells. Both copies of Ppia were disrupted in murine
      embryonic stem (ES) cells via gene targeting. Ppia(-/-) ES cells grow normally
      and differentiate into hematopoeitic precursor cells in vitro, indicating that
      CyPA is not essential for mammalian cell viability.

PMID- 10964516
TI  - Evolution, structure, and expression of GNPI/Oscillin orthologous genes.
AB  - Oscillin was identified from hamster sperm as a factor responsible for oocyte
      calcium oscillations. However, its high level of homology with the bacterial
      glucosamine-6-phosphate isomerase suggests that it may play more fundamental
      roles. In the current study, we identified Oscillin orthologs from Caenorhabditis
      elegans, Drosophila melanogaster, mouse, and human. Their amino acid identities
      with hamster oscillin were 67.0, 72.3, 97.6, and 95.5%, respectively. No Oscillin
      orthologs were found in Saccharomyces cerevisiae. The human Oscillin gene (HGMW
      approved symbol GNPI) spans 12.4 kb and consists of eight exons. The position of
      the fourth intron was conserved in other species. The human Oscillin promoter has
      features characteristic of housekeeping genes, including a GC-rich content,
      multiple SP1 binding sites, and the absence of a TATA motif. Human and mouse
      Oscillin genes were ubiquitously expressed in all tissues examined. These data
      showed that Oscillin is a housekeeping gene conserved throughout evolution and do
      not support the notion that Oscillin is the sperm-specific factor responsible for
      calcium oscillations.

PMID- 10964517
TI  - Isolation and characterization of two evolutionarily conserved murine kinases
      (Nek6 and nek7) related to the fungal mitotic regulator, NIMA.
AB  - Entrance and exit from mitosis in Aspergillus nidulans require activation and
      proteolysis, respectively, of the NIMA (never in mitosis, gene A)
      serine/threonine kinase. Four different NIMA-related kinases were reported in
      mammals (Nek1-4), but none of them has been shown to perform mitotic functions
      related to those demonstrated for NIMA. We describe here the isolation of two
      novel murine protein kinase genes, designated nek6 and nek7, which are highly
      similar to each other (87% amino acid identity in the predicted kinase domain).
      Interestingly, Nek6 and Nek7 are also highly similar to the F19H6.1 protein
      kinase of Caenorhabditis elegans (76 and 73% amino acid identity in the kinase
      domain, respectively), and phylogenetic analysis suggests that these three
      proteins constitute a novel subfamily within the NIMA family of serine/threonine
      kinases. In contrast to the other documented NIMA-related kinases, Nek6/7 and
      F19H6.1 harbor their catalytic domain in the C-terminus of the protein.
      Immunofluorescence suggests that Nek6 and Nek7 are cytoplasmic. Linkage analysis,
      using the murine BXD recombinant inbred strain panel, localized nek6 to
      chromosome 2 at 28 cM. Using a mouse/hamster radiation hybrid panel, we assigned
      the nek7 gene to chromosome 1 at approximately 73 cM.

PMID- 10964518
TI  - Identification of differentially expressed genes in epithelial stem/progenitor
      cells of fetal rat liver.
AB  - Differentially expressed cDNA clones from fetal rat liver were isolated using
      suppression subtractive hybridization, combined with an efficient screening
      strategy. Approximately 30,000 clones were screened, yielding 643 genes whose
      expression was induced, of which 201 clones were distinct and 68 represented ESTs
      or newly discovered genes of unknown function. Based on their expression patterns
      in different organs, fetal liver, liver regeneration models, and gut epithelial
      progenitor cell lines, the subtracted clones presented in this work were placed
      into four categories: (1) hepatoblast-specific genes; (2) hematopoietic cell
      specific genes; (3) genes expressed in hepatoblasts, in hematopoietic cells, and
      at varying levels in other tissues; and (4) genes overexpressed in fetal liver,
      in models of activation of liver progenitor cells, and in epithelial progenitor
      cell lines. Hepatoblast-specific clones and those representing genes induced
      during liver regeneration are under further study to define their specific
      function(s) in liver cell growth control and/or differentiation.

PMID- 10964519
TI  - Cloning, expression, and chromosome mapping of the murine Hip/Rpl29 gene.
AB  - We previously have identified murine heparin/heparan sulfate-interacting protein
      (HIP) identical to mouse ribosomal protein L29 that is, like its human
      orthologue, distinctively expressed both on the cell surface and intracellularly
      in different adult tissues and cell types. In the present study, we show that
      mouse HIP/RPL29 is encoded by a single mRNA and that it is expressed to different
      extents in most of the tissues of the developing embryo without restriction to a
      specific cell type. We isolated the single-copy gene coding for murine Hip/Rpl29
      among a large number of pseudogenes, established its structure, and assigned its
      location to distal chromosome 9. Similar to other ribosomal protein promoters,
      the promoter of Hip/Rpl29 is rich in polypyrimidine tracts, contains binding
      motifs for ubiquitously expressed transcription factors, and lacks a TATA box.
      Progressive 5' deletion analyses identified a strong enhancer region that
      includes CT-rich sequences and a potential consensus binding site for NF-kappaB.
      These data will provide valuable tools to progress the understanding of HIP/RPL29
      function as a ribosomal protein and/or as a regulator of growth and cell adhesion
      through interaction with heparan sulfate proteoglycans.

PMID- 10964520
TI  - A physical and transcript map based upon refinement of the critical interval for
      PPH1, a gene for familial primary pulmonary hypertension. The International PPH
      Consortium.
AB  - Primary pulmonary hypertension (PPH), an often fatal disorder, is characterized
      by sustained elevation of pulmonary artery pressure of unknown cause. In its
      familial form (FPPH), the disorder segregates as an autosomal dominant and
      displays markedly reduced penetrance. A gene for FPPH was previously localized to
      a 25-cM interval on the long arm of chromosome 2 (2q31-q33). We now report a
      complete yeast artificial chromosome (YAC) and bacterial artificial chromosome
      (BAC)/P1 artificial chromosome contig (PAC), assembled by STS content mapping,
      across a newly identified minimum nonrecombinant interval containing the gene
      designated PPH1. The physical map has served to establish polymorphic marker
      order unequivocally, enabling the establishment of detailed haplotypes for the
      region. Together with the identification of novel recombination events in
      affected individuals from six newly ascertained kindreds, these data have allowed
      the significant reduction of the minimum PPH1 critical interval to a 4.8-cM
      region. The region, flanked by the polymorphic markers D2S115 (centromeric) and
      D2S1384 (telomeric), corresponds to a minimum physical distance of 5.8 Mb at
      2q33. Numerous expressed sequence tags and known genes were placed on the YAC/BAC
      contig spanning the PPH1 gene critical region.

PMID- 10964521
TI  - Vasotocin stimulates appetitive responses to the visual and pheromonal stimuli
      used by male roughskin newts during courtship.
AB  - It is now well established that vasotocin (AVT) and its mammalian homologue
      vasopressin influence various social behaviors in vertebrates, but less is known
      about the mechanisms through which these peptides modulate behavior. In male
      roughskin newts, Taricha granulosa, AVT stimulates a courtship behavior,
      amplectic clasping. Three general explanations for how AVT affects male courtship
      behavior have been considered: by enhancing a central state of sexual motivation,
      by affecting sensorimotor integration mechanisms in individual sensory
      modalities, or by influencing a nonspecific state of attention, arousal, or
      anxiety. AVT administration enhanced appetitive responses to visual and olfactory
      sexual stimuli, as would be expected if AVT affects a state of sexual motivation
      that affects behavioral responses to sexual stimuli regardless of the sensory
      modality in which they are processed. However, AVT selectively enhanced responses
      to female olfactory stimuli (sex pheromones), but similarly enhanced responses to
      female and food-related visual stimuli (worms), thus questioning the utility of
      such a motivational mechanism, as responses to female stimuli were not
      selectively enhanced in all sensory modalities. We therefore propose that
      exogenous AVT independently influences olfactory processes associated with
      orientation/attraction toward a female sex pheromone and visual processes
      associated with orientation/attraction toward a visual feature common to females
      and worms. In further experiments AVT administration failed to stimulate feeding
      behavior but did decrease locomotor activity. Thus, AVT does not stimulate
      courtship behavior in this species by enhancing the animals' general state of
      attention or by decreasing general anxiety, as responses to nonsexual, attractive
      stimuli were not uniformly enhanced, nor by stimulating general arousal, as
      activity levels did not increase. Rather, the data support the conclusion that
      AVT affects courtship by influencing specific sensorimotor processes associated
      with behavioral responses to individual releasing stimuli, which suggests a
      mechanistic framework for understanding socially motivated behavior is this
      species.

PMID- 10964522
TI  - Estrogen in the medial preoptic area of male rats facilitates copulatory
      behavior.
AB  - Mating was studied in sexually experienced, gonadally intact male rats assigned
      to two surgical groups matched on the basis of mean mounting frequency during
      behavioral screening trials conducted prior to the study. Estradiol (E(2)) was
      delivered bilaterally into the medial preoptic area (MPO) of experimental males
      by means of hormone-coated implants, and fadrozole was given sc (0.25 mg/kg/day)
      via osmotic minipumps to block E(2) formation from testicular testosterone
      throughout the brain. Control males received blank bilateral implants in the MPO
      and sc fadrozole. After the completion of behavioral testing, immunocytochemical
      comparisons of the brains from experimental and control rats were made using the
      H222 antiestrogen receptor (ER) antibody, whose labeling is inhibited by the
      presence of E(2). The histology demonstrated that E(2) was confined exclusively
      to the MPO of experimental males but was absent throughout the brains of
      controls. In controls, mounting decreased significantly by the 7th day after
      surgery compared with presurgical levels and did not recover. In contrast, on all
      postsurgical days, the mounting frequency of the experimental group was
      significantly higher than that of controls. Although experimental males also
      showed an initial, significant postsurgical decline in mounting frequency, it
      recovered completely by the 28th postoperative day. Ejaculations declined
      significantly after surgery in both groups but, unlike in controls whose
      performance remained low, ejaculations in experimental males partially recovered
      and were significantly higher than in controls during the postoperative period.
      Results showed that ER-containing neurons in the MPO influence male rat
      copulatory behavior.

PMID- 10964523
TI  - Can pseudo entrainment explain the synchrony of estrous cycles among golden
      hamsters (Mesocricetus auratus)?
AB  - Synchrony among golden hamsters is often cited in the menstrual-cycle synchrony
      literature and has recently become a paradigm for explaining menstrual synchrony
      in humans (L. Weller, A. Weller, and S. Roizman (1999), J. Comp. Psychol. 113,
      261-268). It has also stimulated further research on synchrony in Djungarian
      hamsters, for which no evidence of synchrony was found (G. E. Erb, H. E. Edwards,
      K. L. Jenkins, L. C. Mucklow, and K. E. Wynne-Edwards (1993), Physiol. Behav. 54,
      955-959). The case for synchrony in the golden hamster is reexamined in this
      paper. It is demonstrated, with the help of computer simulation experiments, that
      the experimental method used by G. Handelmann, R. Ravizza, and W. J. Ray (1980,
      Horm. Behav. 14, 107-115) for detecting synchrony has a critical flaw. It does
      not distinguish synchrony that can occur by chance (pseudo entrainment) from
      synchrony due to a process of entrainment. It is suggested that the apparent
      entrainment of estrous cycles in hamsters and the role of social dominance may be
      due to the stress caused by moving animals to different rooms or grouping them.
      Thus, because we cannot reject the possibility of pseudo entrainment as an
      explanation for these results, it must be concluded that there is no evidence
      that golden hamsters synchronize their estrous cycles. Finally, an approach is
      briefly outlined for testing synchrony in golden hamsters.

PMID- 10964524
TI  - Short-day increases in aggression are inversely related to circulating
      testosterone concentrations in male Siberian hamsters (Phodopus sungorus).
AB  - Many nontropical rodent species display seasonal changes in both physiology and
      behavior that occur primarily in response to changes in photoperiod. Short-day
      reductions in reproduction are due, in part, to reductions in gonadal steroid
      hormones. In addition, gonadal steroids, primarily testosterone (T), have been
      implicated in aggression in many mammalian species. Some species, however,
      display increased aggression in short days despite basal circulating
      concentrations of T. The goal of the present studies was to test the effects of
      photoperiod on aggression in male Siberian hamsters (Phodopus sungorus) and to
      determine the role of T in mediating photoperiodic changes in aggression. In
      Experiment 1, hamsters were housed in long and short days for either 10 or 20
      weeks and aggression was determined using a resident-intruder model. Hamsters
      housed in short days for 10 weeks underwent gonadal regression and displayed
      increased aggression compared to long-day-housed animals. Prolonged maintenance
      in short days (i.e., 20 weeks), however, led to gonadal recrudescence and reduced
      aggression. In Experiment 2, hamsters were housed in long and short days for 10
      weeks. Half of the short-day-housed animals were implanted with capsules
      containing T whereas the remaining animals received empty capsules. In addition,
      half of the long-day-housed animals were castrated whereas the remaining animals
      received sham surgeries. Short-day control hamsters displayed increased
      aggression compared to either castrated or intact long-day-housed animals. Short
      day-housed T treated hamsters, however, did not differ in aggression from long
      day-housed animals. Collectively, these results confirm previous findings of
      increased aggression in short-day-housed hamsters and suggest that short-day
      induced increases in aggression are inversely related to gonadal steroid
      hormones.

PMID- 10964526
TI  - Progesterone inhibits female courtship behavior in domestic canaries (Serinus
      canaria).
AB  - We studied copulation solicitation display (CSD) responses to playback in
      photostimulated female canaries given systemic injections of progesterone. Eight
      females received injections of 0.1 mg of progesterone dissolved in olive oil
      during their first breeding cycle and were untreated during their second breeding
      cycle; eight females received only the oil vehicle during their first breeding
      cycle and received no treatment during their second breeding cycle. The
      injections were performed every second day during 15 days, after the onset of
      nest building. Progesterone treatment resulted in a significant increase of
      plasma progesterone which in turn provoked an inhibition of females' CSDs and
      decreased the size of the clutch. During the first breeding cycle, progesterone
      treated females had lower CSDs and egg-laying scores than did control females.
      During the second breeding cycle, when females received no treatment, no
      differences emerged between the two groups. The suppressive effect of
      progesterone on female sexual responses was observed as soon as 48 h after the
      beginning of the treatment. We propose that progesterone plays a key role in
      mediating the transition from active female courtship behavior to sexual
      refractoriness in this species. Suppressive effects of progesterone on female
      sexual behavior have been previously described in lizards as well as in rodents.
      Our data are consistent with the hypothesis of Godwin et al. (J. Godwin, V.
      Hartman, M. Grammer, and D. Crews, Horm. Behav. 30, 138-144, 1996) which proposed
      that the decrease in sexual behavior following plasma progesterone increase
      represents an evolutionarily conserved mechanism in the regulation of female
      sexual behavior.

PMID- 10964525
TI  - Prolactin levels during the periparturitional period in the biparental cotton-top
      tamarin (Saguinus oedipus): interactions with gender, androgen levels, and
      parenting.
AB  - Unlike biparental bird and rodent species, mating and parenting occur
      simultaneously in cotton-top tamarins, Saguinus oedipus, providing a unique model
      for examining endocrine interactions. This study was designed to determine the
      relationship of prolactin to testicular androgens during parenting and mating.
      Specifically we examined (1) the patterns of postpartum prolactin excretion in
      male and female tamarins with and without infant survival; (2) the relationship
      between androgen and prolactin levels during the periparturitional period in male
      tamarins; and (3) male hormonal response to the postpartum mating that occurs
      simultaneously with paternal care. All females showed an elevation in prolactin
      during the first week postpartum and when infants died, female prolactin levels
      decreased significantly. Infant survival during the first 15 days did not
      influence male levels of prolactin, cortisol, or the testicular androgens
      testosterone and dihydrotestosterone (DHT). Prolactin did not show an inverse
      relationship with any of the androgens (testosterone, DHT) studied during the
      postpartum period. No significant differences in hormones were found between
      prepartum levels and the first, second, and third 5-day blocks postpartum for all
      10 males. Males who had infant-care experience showed an increase in testosterone
      during the first 5 days postpartum and prolactin levels correlated with the
      number of previous births a male had experienced. However, the most significant
      changes in testosterone occurred in males whose mates ovulated during the first
      15 days following birth in contrast to males whose mates ovulated later than 15
      days. These results indicate that unlike females, male tamarins are not showing
      hormonal changes in response to infants. Urinary androgens did not show an
      inverse relationship to prolactin in male tamarins, but were elevated concurrent
      with the female's fertile period.

PMID- 10964527
TI  - Effects of male rat urine on reproductive and developmental parameters in the dam
      and her female offspring.
AB  - This study investigated the direct and indirect effects of male Norway rat
      (Rattus norvegicus) urine on reproductive, developmental, and fecundity
      parameters in the dam and her female offspring. Twenty-two dams and litters were
      studied: 11 in male urine and 11 in distilled water conditions. Only dams were
      exposed to male urine (or distilled water) from days 14 to 29 postpartum.
      Significant effects found for the dams exposed to male urine (compared to those
      only exposed to distilled water) included (i) the second lactational estrus was
      delayed by 2 days, (ii) vaginal opening and first estrus were 1 day later for
      female offspring, (iii) the first estrous cycle after vaginal opening was also
      shorter for their offspring, and (iv) female offspring subsequently produced
      larger litters than female offspring from dams only exposed to distilled water.
      Thus, urine from males had direct effects on the timing of the second lactational
      estrus in dams and indirect effects (mediated by the dam) on developmental and
      reproductive parameters of her female offspring. Taken as a whole, these results
      suggest that pheromones in Norway rats may be complex in their effects, context
      dependent, and only fully revealed in ecologically relevant contexts. Further
      study is required to determine whether these effects occur and have biological
      functions in natural populations.

PMID- 10964529
TI  - The position of the Nazlet Khater specimen among prehistoric and modern African
      and Levantine populations.
AB  - The morphometric affinities of the 33,000 year old skeleton from Nazlet Khater,
      Upper Egypt are examined using multivariate statistical procedures. In the first
      part, principal components analysis is performed on a dataset of mandible
      dimensions of 220 fossils, sub-fossils and modern specimens, ranging in time from
      the Late Pleistocene to recent and restricted in space to the African continent
      and Southern Levant. In the second part, mean measurements for various
      prehistoric and modern African and Levantine populations are incorporated in the
      statistical analysis. Subsequently, differences between male and female means are
      examined for some of the modern and prehistoric populations. The results indicate
      a strong association between some of the sub-Saharan Middle Stone Age (MSA)
      specimens, and the Nazlet Khater mandible. Furthermore, the results suggest that
      variability between African populations during the Neolithic and Protohistoric
      periods was more pronounced than the range of variability observed among recent
      African and Levantine populations. Results also demonstrate a general reduction
      in the degree of sexual dimorphism during the Holocene. However, this pattern of
      reduction pattern varies by geographic location and is not uniform across the
      African continent.

PMID- 10964528
TI  - Assessing estradiol in biobehavioral studies using saliva and blood spots: simple
      radioimmunoassay protocols, reliability, and comparative validity.
AB  - We developed simple, reliable, and highly sensitive assay modifications of
      commercially available radioimmunoassay kits to measure estradiol in saliva and
      blood spot specimens. The saliva assay has average intra- and interassay
      coefficients of variation (CV) of 6.45 and 9.01%, with average analytical and
      serial dilution recoveries 100.65 and 89.25%. The blood spot assay has average
      intra- and interassay CVs of 7.57 and 8.22%, with analytical and serial dilution
      recoveries of 80.50 and 108.50%. The analytical sensitivity ranges of the saliva
      (0.25-7.50 pg/ml) and blood spot (2. 00-375 pg/ml) assays are sufficient to
      determine levels in the majority of pre- and postpubertal males and females.
      Blood spot assay results are correlated with serum estradiol levels for adult
      males, r (17) = 0.73, and females, r (18) = 0.96. In contrast, the serum-saliva
      correlation is only modest for adult females, r (14) = 0.60, and not significant
      for adult males. Substitution of blood spot assay results for serum values
      underestimates the known serum estradiol-behavior correlation by only 3.45%,
      whereas substitution of saliva assay results for serum values underestimates the
      association by 37.55%. The findings have important implications for the use and
      potential misuse of noninvasive measures of estradiol in studies of health and
      human development.

PMID- 10964530
TI  - Estimating missing data: an iterative regression approach.
AB  - The problem of missing data is common in all fields of science. Various methods
      of estimating missing values in a dataset exist, such as deletion of cases,
      insertion of sample mean, and linear regression. Each approach presents problems
      inherent in the method itself or in the nature of the pattern of missing data. We
      report a method that (1) is more general in application and (2) provides better
      estimates than traditional approaches, such as one-step regression. The model is
      general in that it may be applied to singular matrices, such as small datasets or
      those that contain dummy or index variables. The strength of the model is that it
      builds a regression equation iteratively, using a bootstrap method. The precision
      of the regressed estimates of a variable increases as regressed estimates of the
      predictor variables improve. We illustrate this method with a set of measurements
      of European Upper Paleolithic and Mesolithic human postcranial remains, as well
      as a set of primate anthropometric data. First, simulation tests using the
      primate data set involved randomly turning 20% of the values to "missing". In
      each case, the first iteration produced significantly better estimates than other
      estimating techniques. Second, we applied our method to the incomplete set of
      human postcranial measurements. MISDAT estimates always perform better than
      replacement of missing data by means and better than classical multiple
      regression. As with classical multiple regression, MISDAT performs when squared
      multiple correlation values approach the reliability of the measurement to be
      estimated, e.g., above about 0. 8.

PMID- 10964531
TI  - A comparison of primate, carnivoran and rodent limb bone cross-sectional
      properties: are primates really unique?
AB  - The cross-sectional properties of mammalian limb bones provide an important
      source of information about their loading history and locomotor adaptations. It
      has been suggested, for instance, that the cross-sectional strength of primate
      limb bones differs from that of other mammals as a consequence of living in a
      complex arboreal environment (Kimura, 1991, 1995). In order to test this
      hypothesis more rigorously, we have investigated cross-sectional properties in
      samples of humeri and femora of 71 primate species, 30 carnivorans and 59
      rodents. Primates differ from carnivorans and rodents in having limb bones with
      greater cross-sectional strength than mammals of similar mass. This might imply
      that primates have stronger bones than carnivorans and rodents. However, primates
      also have longer proximal limb bones than other mammals. When cross-sectional
      dimensions are regressed against bone length, primates appear to have more
      gracile bones than other mammals. These two seemingly contradictory findings can
      be reconciled by recognizing that most limb bones experience bending as a
      predominant loading regime. After regressing cross-sectional strength against the
      product of body mass and bone length, a product which should be proportional to
      the bending moments applied to the limb, primates are found to overlap
      considerably with carnivorans and rodents. Consequently, primate humeri and
      femora are similar to those of nonprimates in their resistance to bending.
      Comparisons between arboreal and terrestrial species within the orders show that
      the bones of arboreal carnivorans have greater cross-sectional properties than
      those of terrestrial carnivorans, thus supporting Kimura's general notion.
      However, no differences were found between arboreal and terrestrial rodents.
      Among primates, the only significant difference was in humeral bending rigidity,
      which is higher in the terrestrial species. In summary, arboreal and terrestrial
      species do not show consistent differences in long bone reinforcement, and
      Kimura's conclusions must be modified to take into account the interaction of
      bone length and cross-sectional geometry.

PMID- 10964532
TI  - Inferring social behavior from sexual dimorphism in the fossil record.
AB  - Sexual dimorphism is commonly used as evidence of the behavior of extinct
      species. Even so, few analyses scrutinize whether extant comparative data support
      inferences of mating systems or behavior in extinct species. This analysis
      evaluates the relations between measures of dimorphism and several estimates of
      mating system and intrasexual competition. Dimorphism alone provides poor
      resolution for reconstructing behavior. Many behavioral inferences based on
      perceived dimorphism are not supported by extant comparative data. This reflects
      the large standard errors of relations between dimorphism estimates and
      behavioral classifications. Used with caution, dimorphism can provide a hint of
      the behavior of extinct species in some cases. However, in many cases inferred
      dimorphism allows little more than an inference of polygyny, without any
      indication of specific types of mating systems.

PMID- 10964534
TI  - The immune tolerance network--an NIH/JDF-supported initiative to bring tolerance
      research into the clinic: a major new resource for clinical immunologists.

PMID- 10964533
TI  - Analysis of a bone assemblage made by chimpanzees at Gombe National Park,
      Tanzania.
AB  - Chimpanzee hunting provides information on prey characteristics and constraints
      acting on a large-bodied primate lacking a hunting technology, and has important
      implications for modeling hunting by fossil hominids. Analysis of the remains of
      five red colobus monkeys captured and consumed by Gombe chimpanzees in a single
      hunting bout provides one of the first opportunities to investigate the
      characteristics of prey bones surviving chimpanzee consumption. Four of the five
      individuals (an older infant, two juveniles and one subadult) were preserved in
      the bone assemblage; a neonate was entirely consumed. Cranial and mandibular
      fragments had the highest survivorships, followed by the scapulae and long bones.
      Post-cranial axial elements had the lowest survivorships. A high percentage (80%)
      of the long bones and ribs surviving consumption were damaged, most commonly
      through crenulation and step fracturing of bone ends. One of two partially
      reconstructed crania preserves a canine puncture through its left parietal.
      Proposed characteristics of faunal assemblages formed through chimpanzee-like
      hunting include small modal prey size, limited taxonomic diversity, a high
      proportion of immature individuals and a high frequency of skull bones. These
      characteristics would not uniquely identify hunting by fossil primates in the
      geological record, necessitating a contextual approach to diagnose hunting by
      hominids not forming an archeological record. Hominid utilization of vertebrate
      tissue is first unambiguously documented at 2.5 m.y.a. Rather than representing a
      strict "scavenging phase" in the evolution of hominid-prey interactions, Oldowan
      hominid carnivory may represent the overlay of large mammal scavenging on a
      tradition of small mammal hunting having a low archeological visibility.

PMID- 10964535
TI  - Immunopathogenesis of Behcet's disease.

PMID- 10964536
TI  - Response differences between human CD4(+) and CD8(+) T-cells during CD28
      costimulation: implications for immune cell-based therapies and studies related
      to the expansion of double-positive T-cells during aging.
AB  - Since CD28 costimulation is critical for T-cell activation, there is great
      interest in CD28 as a target for immuntherapeutic approaches. We show that
      stimulation of human CD4(+) and CD8(+) T-cells differs in their responsiveness to
      stimulation with anti-CD3/CD28-coated beads, as surrogate antigen-presenting
      cells. While the CD4(+) subset responded with sustained proliferation, CD8(+) T
      cells grew for a limited period only and failed to produce IL-2 beyond the first
      few days in culture. This decrease is accompanied with an increased rate of
      apoptosis in CD8(+) T-cells despite Bcl-x(L) expression. The CD8(+) but not the
      CD4(+) subset developed a reversible double-positive phenotype during CD28
      costimulation. This finding may have some bearing on the appearance of double
      positive T-cells in human peripheral blood. This double-positive subset was shown
      to undergo a statistically significantly increase during aging in humans. Taken
      together, the above data have important implications for immunotherapy and immune
      senescence.

PMID- 10964537
TI  - Inhibition of murine macrophage IL-12 production by natural and synthetic DNA.
AB  - DNA is a complex macromolecule whose immunological properties vary with sequence
      and structure. To determine whether DNA can inhibit immune responses, the effects
      of mammalian DNA and synthetic phosphodiester (Po) and phosphorothioate (Ps)
      oligonucleotides (ODNs) on IL-12 production were tested using murine macrophages.
      With bacterial DNA as a stimulant, calf thymus DNA and human placenta DNA blocked
      IL-12 production by splenic and bone marrow macrophages. A (dG)(30) Po ODN and
      all single-base Ps 30 mer ODNs were also effective inhibitors. The Ps ODNs also
      blocked IL-12 production induced by lipopolysaccharide (LPS) and a stimulatory Ps
      ODN. With the J774 cell line, single-base Ps ODNs inhibited IL-12 production
      induced by bacterial DNA, LPS, and a stimulatory Ps ODN. Together, these results
      indicate that DNA has inhibitory properties, suggesting that mammalian DNA could
      limit immune activation during inflammation and counteract the effects of
      bacterial DNA.

PMID- 10964538
TI  - Combined nasal administration of encephalitogenic myelin basic protein peptide 68
      86 and IL-10 suppressed incipient experimental allergic encephalomyelitis in
      Lewis rats.
AB  - Mucosal administration of low doses of myelin basic protein (MBP) peptide 68-86
      (MBP 68-86) or anti-inflammatory cytokine IL-10 effectively prevented
      experimental allergic encephalomyelitis (EAE), but failed to suppress the disease
      if given after 7 days postimmunization (p.i.), i.e., after T cell priming had
      occurred. We anticipated that combined administration of autoantigen and IL-10
      can treat incipient EAE. Lewis rats with EAE actively induced with MBP 68-86 and
      complete Freund's adjuvant received 120 microg MBP 68-86 + 200 ng IL-10 per rat
      per day from day 7 p.i. and for 5 consecutive days. These rats showed later
      onset, lower clinical scores, less body weight loss, and shorter duration of EAE
      than rats receiving MBP 68-86 or IL-10 only or PBS. EAE amelioration was
      associated with decreased infiltration of ED1(+) macrophages and CD4(+) T cells
      within the central nervous system and with decreased proliferative responses of
      lymph node cells, indicating that combined administration of MBP 68-86 and IL-10
      induced immune hyporesponsiveness. IFN-gamma secretion as well as IFN-gamma, TNF
      alpha, IL-4, and IL-10 mRNA expression by lymph node MNC was down-regulated in
      the treated rats. Immune hyporesponsiveness, rather than immune deviation or
      regulatory mechanisms, seems to be responsible for the protection of EAE after
      autoantigen + IL-10 administration by the nasal route.

PMID- 10964539
TI  - Inhibition of heparin/protamine complex-induced complement activation by
      Compstatin in baboons.
AB  - Complement activation products are major components of the inflammatory response
      induced by cardiac surgery and cardiopulmonary bypass which contribute to
      postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of
      the complement system occurs during extracorporeal circulation, during
      reperfusion of ischemic tissue, and after the formation of heparin-protamine
      complexes. In this study we examine the efficacy of Compstatin, a recently
      discovered peptide inhibitor of complement, in preventing heparin/protamine
      induced complement activation in baboons. The study was performed in baboons
      because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in
      baboon blood (similar to humans); Compstatin inhibits only the activation of
      primates' complement system. After testing various doses and administration
      regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg
      when given as a combination of bolus injection and infusion. Compstatin
      completely inhibited in vivo heparin/protamine-induced complement activation
      without adverse effects on heart rate or systemic arterial, central venous, and
      pulmonary arterial pressures. This study indicates that Compstatin is a safe and
      effective complement inhibitor that has the potential to prevent complement
      activation during and after clinical cardiac surgery. Furthermore, Compstatin can
      serve as the prototype for designing an orally administrated drug.

PMID- 10964540
TI  - Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis.
AB  - Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+)
      T-cells from immunocompetent syngenic donor mice. As the disease progresses,
      immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting
      that locally accumulating Ig may play a role in disease development. In the
      present work we have investigated the relationship between disease progression
      and patterns or levels of Ig isotypes in the feces of scid mice suffering from an
      ongoing colitis. The data clearly showed that the severity or progression of the
      disease did not influence the levels of IgA, IgG1, IgG2a, IgG2b, and IgG3,
      whereas the level of fecal IgM increased during the course of colitis. The
      presence of the serum protein alpha-1-antitrypsin in fecal extracts from diseased
      mice suggests that some of the fecal Ig has leaked through the inflamed
      epithelial membrane into the gut lumen. Finally, Ig-containing cells were
      observed in mesenteric lymph nodes and in the spleen, suggesting that the fecal
      Ig is produced both systemically and locally in the gut wall. In conclusion, the
      present results demonstrate that the level of IgM increases as colitis
      progresses. Also, the five remaining major Ig isotypes are increased in the gut
      lumen of scid mice with colitis, but the individual Ig types vary randomly during
      the course of the disease. Thus, it is unlikely that immunoglobulins are involved
      in the immunopathogenesis of this model of colitis.

PMID- 10964541
TI  - The increase of IFN-gamma production through aging correlates with the expanded
      CD8(+high)CD28(-)CD57(+) subpopulation.
AB  - The use of flow cytometry to detect intracellular cytokines at the single cell
      level has the potential to quantify cytokine production together with the
      possibility of phenotypic identification of the cell population concerned. The
      unbalanced presence of intracellular cytokines produced by T cells has been
      recognized in some pathological conditions. To better address this issue, we
      studied the production of IFN-gamma and IL-4 in CD4(+) and CD8(+high) T cells in
      healthy donors of a broad range of age (17-62 years). Given that an increase of
      IFN-gamma and IL-4 with aging had been reported by some authors in healthy
      controls, we have performed a multivariate analysis to assess the intrinsic role
      of aging or of other external factors, such as chronic antigenic exposures (i.e.,
      viruses), over the cytokine production of phenotypically characterized T cells.
      In this respect we show that, mainly in CD8(+high) T cells, the production of IFN
      gamma is directly correlated with age. Besides, the cytokine production
      correlates with the CD8(+high)CD28(-)CD57(+) T-cell population, which we have
      recently reported elevated in aged individuals. Perhaps this T-cell subpopulation
      plays a regulatory role as a Tc1 response in aging individuals.

PMID- 10964542
TI  - N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein
      gp41, is an activator of human phagocytes.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral
      fusion with human host cells. In this study we show that N36, a synthetic peptide
      derived from the N-terminus of gp41, induced directional migration and calcium
      mobilization in human monocytes and neutrophils. The activity of N36 on
      phagocytes was pertussis toxin sensitive, suggesting involvement of a Gi-coupled
      seven-transmembrane receptor(s). Since high concentrations of the bacterial
      chemotactic peptide fMet-Leu-Phe (fMLF) partially desensitized the calcium
      mobilizing activity of N36 in phagocytes, we postulated that N36 might use a low
      affinity fMLF receptor. By using cells stably expressing fMLF receptor FPR or
      FPRL1, we demonstrate that N36 uses FPRL1 as a functional receptor. Our results
      suggest that HIV-1 gp41 may contain a fragment(s) that activates the innate host
      immune cells through FPRL1. Since the activation of FPRL1 in monocytes has been
      shown to heterologously desensitize chemokine receptors, the reduced phagocyte
      response to chemoattractants seen in AIDS patients may be attributed, at least in
      part, to heterologous desensitization.

PMID- 10964543
TI  - Activation of human microglial cells by HIV-1 gp41 and Tat proteins.
AB  - The viral proteins, Tat (HIV-1 nuclear protein) and gp41 (HIV-1 coat protein),
      detected in the brains of HIV-1-infected patients have been shown to be
      neurotoxic. We investigated the effects of HIV-1 Tat and gp41 proteins on
      cytokine, chemokine, and superoxide anion (O(-)(2)) production by microglia, the
      resident macrophages of the brain. Tat and gp41 dose-dependently stimulated
      cytokine and chemokine production by microglia. Peak production of these
      cytokines and chemokines differed in microglial cells treated with gp41 and Tat.
      Expression of cytokine and chemokine mRNA was also stimulated in gp41- and Tat
      treated microglia. Neither gp41 nor Tat alone stimulated O(-)(2) production by
      microglia. Treatment of microglial cells with Tat but not with gp41 evoked an
      increase in intracellular Ca(2+). The results of this study suggest that HIV-1
      Tat and gp41 proteins impact several key functions of microglial cells which
      could contribute to the neuropathogenesis of HIV-1.

PMID- 10964544
TI  - Acidic pH inhibits non-MHC-restricted killer cell functions.
AB  - Immunotherapeutic strategies in advanced stages of solid tumors have generally
      met with little success. Various mechanisms have been discussed permitting the
      escape of tumor cells from an effective antitumoral immune response. Solid tumors
      are known to develop regions with acidic interstitial pH. In a recent study
      performed in the human system, we were able to demonstrate that non-MHC
      restricted cytotoxicity is inhibited by an acidic microenvironment. To get more
      insight into the mechanisms leading to this reduced cytotoxic activity, we have
      now investigated the influence of an acidic extracellular pH (pH(e)) on the
      killing process in detail. Unstimulated PBMC and LAK cells were used as effector
      cells. Both populations are able to kill tumor cells in a MHC-independent manner
      via perforin/granzymes or TNFalpha, whereas only IL-2-activated cells can use the
      killing pathway via Fas/FasL. We studied the influence of a declining pH(e) on
      the different killing pathways against TNFalpha-sensitive and -resistant, as well
      as Fas-positive and -negative, target cells. Experiments in the absence of
      extracellular Ca(2+) were used to discriminate the Ca(2+)-dependent perforin
      mediated killing. Here we show that the release of perforin/granzyme-containing
      granules, the secretion of TNFalpha, and also the cytotoxic action of Fas/FasL
      interaction or of membrane-bound TNFalpha were considerably inhibited by
      declining pH(e). Furthermore, the secretion of the activating cytokine IFNgamma,
      as well as the release of the down-regulating cytokines IL-10 and TGF-beta(1),
      was strictly influenced by surrounding pH. As a pH(e) of 5.8 resulted in a nearly
      complete loss of cytotoxic effector cell functions without affecting their
      viability, we investigated the influence of pH(e) on basic cellular functions,
      e.g. , mitochondrial activity and regulation of intracellular pH. We found an
      increasing inhibition of both functions with declining pH(e). Therefore, an
      acidic pH(e) obviously impairs fundamental cellular regulation, which finally
      prevents the killing process. In summary, our data show a strict pH(e) dependence
      of various killer cell functions. Thus, an acidic microenvironment within solid
      tumors may contribute to the observed immunosuppression in vivo, compromising
      antitumoral defense and immunotherapy in general, respectively.

PMID- 10964545
TI  - Duffy phenotype does not influence the clinical severity of sickle cell disease.
AB  - The red blood cell Duffy antigen receptor for chemokines serves as a sink for the
      clearance of chemokines such as interleukin-8 (IL-8) from the circulation. We
      analyzed the impact of the Duffy phenotype on sickle cell disease (SCD) severity
      and serum IL-8 levels in 15 Duffy-positive and 36 Duffy-negative sickle cell
      patients. There was no difference in clinical severity between Duffy-positive and
      Duffy-negative sickle cell patients. In asymptomatic sickle cell patients the
      upward deviation of mean serum IL-8 levels was significantly greater in Duffy
      negatives (n = 20) than in Duffy-positives (n = 8) (P = 0.011). However, during a
      vasoocclusive episode, serum IL-8 levels were similar between Duffy-negatives (n
      = 11) and Duffy-positives (n = 3). Although the Duffy phenotype seems to
      influence steady-state serum IL-8 levels, it does not seem to have an effect on
      SCD severity.

PMID- 10964546
TI  - Characterization of human anti-acetylcholine receptor monoclonal autoantibodies
      from the peripheral blood of a myasthenia gravis patient using combinatorial
      libraries.
AB  - Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against
      the nicotinic acetylcholine receptor (AChR). Using phage-display technology we
      have characterized the largest panel of anti-AChR monoclonal antibodies thus far
      isolated from a single patient. Despite having been isolated with either Torpedo
      AChR or a human peptide, the recombinant antibodies shared with the donor's serum
      the ability to recognize human AChR expressed in its native configuration on the
      surface of TE671 cells. Their specificity for the main immunogenic region (MIR)
      of the AChR was demonstrated using a synthetic peptide corresponding to the
      region 67-76 of the human AChR alpha subunit and by inhibition of a highly
      pathogenic rat anti-MIR monoclonal antibody (mAb35). This work demonstrates the
      value of combinatorial libraries in isolating pathogenic autoantibodies from
      peripheral blood lymphocytes. Future genetic, structural, and functional analyses
      of the monoclonal antibodies reported herein should enhance our understanding of
      the pathogenesis of MG.

PMID- 10964547
TI  - CD4 T lymphocyte activation in BLV-induced persistent B lymphocytosis in cattle.
AB  - Bovine leukemia virus (BLV) is an oncogenic retrovirus in the human T cell
      leukemia virus family. BLV infects B lymphocytes and induces a nonmalignant
      persistent lymphocytosis (PL) and leukemia/lymphoma in cattle. There is evidence
      that CD4 T lymphocytes are activated during BLV infection and promote the
      development of PL. How CD4 T lymphocytes are activated by BLV infection is not
      known. We observed that CD4 T lymphocytes from PL cattle proliferated in the
      presence of autologous, irradiated peripheral blood mononuclear cells (PBMC),
      whereas no proliferation occurred in cell cultures from BLV-infected non-PL
      cattle. Proliferation required direct contact with metabolically active
      irradiated PBMC but was not associated with viral protein expression or inhibited
      by antibodies to BLV. Unexpectedly, B lymphocytes alone failed to account for the
      irradiated PBMC stimulation of CD4 T lymphocytes. These observations and the
      magnitude of the proliferative response suggest that activation is polyclonal and
      involves mechanisms other than BLV antigen-specific stimulation.

PMID- 10964548
TI  - Analysis of 158 frontal sinus fractures: current surgical management and
      complications.
AB  - A retrospective analysis is presented of 158 patients who sustained frontal sinus
      fractures and were subsequently treated in the Division of Maxillofacial Surgery,
      University of Turin, from 1987 to 1998. The fractures were subdivided according
      to involvement of anterior and posterior walls, and of the nasofrontal duct.
      While treatment involving only the anterior wall is well standardized and without
      complications, management of anterior plus posterior wall fractures or involving
      the nasofrontal duct is still controversial. In dislocated posterior wall
      fractures, cranialization and obliteration of the remaining dead space and of the
      nasofrontal ducts using bone grafts, combined with the use of a pericranium flap,
      allow separation of the nasal cavity from the anterior cranial fossa, preventing
      ascending infections and thus reducing the rate of complications. When the
      fracture involves the nasofrontal duct with the posterior wall substantially
      intact, it is better to re-establish patency of the nasofrontal duct with a
      drainage tube and preserve the function of the sinus. A protocol used in the
      management of each group of fractures, clinical and radiological results, timing
      of operation, surgical procedures, outcomes, and long-term complications are all
      discussed.

PMID- 10964549
TI  - Ophthalmic involvement in cranio-facial trauma.
AB  - OBJECTIVES: This is a retrospective descriptive case study which will look into
      the spectrum of ophthalmic involvement in cases with orbital and eye injuries
      after cranio-facial trauma and to analyse the visual and motility outcome.
      MATERIAL: One hundred and four cases with ophthalmic involvement after cranio
      facial trauma that were referred to and seen in the eye department of a tertiary
      teaching hospital in Singapore between 1991-97 were included in the study.
      METHODS: The case records of 104 such patients were traced. The demographic data,
      the mode of injury, the type of fracture sustained and presence of serious eye
      injury were noted. The details about visual acuity, significant diplopia and
      enophthalmos at the first and last visits were charted. Presence of traumatic
      optic neuropathy including the type of treatment given was recorded. RESULTS:
      There was a male preponderance (82%). The industrial accidents were 21%, only
      next to road traffic accidents, which constituted approximately 36.5%. The
      predominant types of fractures seen were blow-out orbital fractures, complex
      fractures comprising of Le-Fort II, III, panfacial and fronto-basilar skull
      fractures. Diplopia was the most common presenting feature (40%) with visual
      acuity disturbance (23% having <6/60) as the next most common finding. Traumatic
      optic neuropathy was seen in 20% of patients and serious eye injury was present
      in 9% of patients. The incidence of traumatic optic neuropathy was significantly
      higher (p<0.001) in patients with complex fractures and fronto-basilar fractures,
      as compared to the blow-out and zygomatico-maxillary fractures. Analysis of final
      results indicated 15% as having significant diplopia in one or more gazes and
      12.5% as having a vision of <6/60. CONCLUSION: Diplopia and visual acuity
      disturbances seem to be the most common ophthalmic presentations in cranio-facial
      trauma. A significant number of patients suffer from poor vision and significant
      diplopia despite treatment.

PMID- 10964550
TI  - Secondary orbital melanomas: analysis of 15 cases.
AB  - Orbital melanomas comprise a heterogeneous group of pigmented tumours originating
      from melanocytes of the ophthalmic tissues, or represent distant metastases of
      cutaneous melanomas to the orbit. They can be classified into primary and
      secondary orbital melanomas. Whereas primary orbital melanomas are extremely
      rare, secondary orbital melanomas are seen more often and usually represent
      massive extrascleral extensions of uveal melanomas. Their diagnosis is difficult
      and controversy exists both about the treatment policy and regarding the
      prognosis. In an effort to clarify some of the aspects of the biological
      behaviour of these intriguing lesions, we retrospectively reviewed all orbital
      melanomas treated in our departments during the last eight years. The records of
      15 patients with massive secondary orbital melanomas treated surgically were
      reviewed and analysed. Eleven of the patients were female and four were male. The
      mean age at the time of surgery was 68 years. Presenting features included
      unilateral orbital mass, often with painless proptosis, conjuctival bleeding,
      acute glaucoma crisis, decreased visual acuity and intermittent diplopia. The
      site of origin was the uveal tract in nine cases, the conjunctiva in three, the
      eyelids in two and the skin of the lower extremity in one patient. All patients
      were treated surgically with various types of orbital exenteration. Additional
      treatment included radiotherapy and chemotherapy. Two patients died from
      intracranial extension of the disease and 10 died from distant metastases. Three
      patients are alive with no evidence of disease. The longest survival was 33
      months and the mean survival was 16.6 months. Early diagnosis and proper
      management of ocular melanoma prevents orbital extension and prolongs patient
      survival. Surgical treatment of secondary orbital melanoma with or without
      adjuvant radiotherapy and/or chemotherapy does not seem to improve patient
      survival when compared with conservative treatment used in other reports.
      However, orbital exenteration is effective for local control of the disease.

PMID- 10964551
TI  - Reconstruction following radical maxillectomy with flaps supplied by the
      subscapular artery.
AB  - The authors present their experience of 27 cases with repairs of defects
      following radical maxillectomies with free flaps. A total of 28 flaps were used
      (five latissimus dorsi, six scapula, 16 combination flaps of scapula and
      latissimus dorsi and one combination of scapula, latissimus dorsi and serratus
      anterior flap). Only one scapula flap was completely lost and in three cases
      where a combination of scapula and latissimus dorsi flap was used, partial
      necrosis of one component occurred. The authors first choice for reconstruction
      is a scapula bone flap raised on the angular artery combined with the latissimus
      dorsi flap. The combination of flaps with a long pedicle and of the bony and
      muscular components provides the surgeon with the option of customizing the flap
      to meet individual patient needs. For intraoral closure the authors prefer the
      latissimus dorsi muscle which rarely requires secondary procedures for prosthesis
      placement following epithelialization and atrophy. The main disadvantage of the
      flap is the difficulty of two teams working simultaneously, thus increasing the
      average operating time. All postoperative corrections and prosthetic
      rehabilitation should be postponed for at least 2 months following surgery
      because of postoperative swelling.

PMID- 10964552
TI  - Involvement of the cavernous sinus by malignant (extracranial) tumour: palliation
      in six cases without surgery.
AB  - Involvement of the cavernous sinus region due to haematogenous spread or by local
      extension of a malignant head and neck tumour does not occur frequently. Six
      patients were treated by external beam radiation with (n=3) or without
      neoadjuvant chemotherapy between December 1989 and February 1996. Manifestations
      of the condition mainly consisted of fifth and sixth cranial nerve deficits
      (n=4). Complete resolution of cranial nerve deficits after therapy occurred in
      two of the four patients with only three individuals having been evaluable. Three
      of the six patients survived for more than 3 years. Thus, palliation can be
      achieved by chemoradiation or radiotherapy alone, and long term survival is not
      precluded.

PMID- 10964553
TI  - 4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.
AB  - Chromosome 4p- syndrome is a multiple malformation syndrome associated with
      partial deletion of the short arm of chromosome 4 (4p-). It is characterized by
      dysmorphic features and retarded development. Cleft lip and/or palate are the
      major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the
      principal clinical manifestations of this condition are characteristic
      craniofacial abnormalities, generalized hypotonia and severe mental retardation.
      We present the first case of a female infant with 4p deletion and tetrasomy 9p
      mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. Karyotype
      analysis of lymphocytes cultured from the patient revealed that she was mosaic:
      86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4)
      (p15.32), +idic (9)(q12). The G-banding pattern appeared consistent with either
      translocation or partial proximal deletion of 4p. In order to make a definitive
      cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ
      hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg,
      her cleft lip was repaired. Before and after surgery there were no seizures, and
      the postoperative course was uneventful.

PMID- 10964554
TI  - Refinement of velopharyngoplasty in patients with cleft palate by covering the
      pharyngeal flap with nasal mucosa from the velum.
AB  - The velopharyngoplasty performed using the popular Sanvenero-Rosselli method
      improves the speech quality of patients with cleft palate suffering from
      persistent velopharyngeal insufficiency despite successful closure of the hard
      and soft palates. However, often a relatively narrow pharyngeal bridge results
      due to healing not only by granulation and scar contraction, but also due to the
      insertion of the inferior tip of the flap into a narrow bed. Elevation of two
      velar flaps with nasal mucosa to cover the exposed muscular undersurface of the
      pharyngeal flap produces a broader recipient bed into which the pharyngeal flap
      can be spread. The speech quality of 27 patients treated with this modified
      method (group B) was compared with that of 27 patients without this modification
      (group A). Eight weeks after velopharyngoplasty (followed by uneventful wound
      healing) the speech quality of group B was significantly better than that of
      group A (p<0.03 MannWhitney U-test). This difference was even more evident when
      comparing the preoperative with the postoperative speech quality (p<0.005). Thus,
      covering the exposed muscular layer of the pharyngeal flap with nasal mucosa of
      the velum is an important modification of velopharyngoplasty for the improvement
      of speech quality.

PMID- 10964555
TI  - The L-shaped osteotomy for vertical callus distraction in the molar region of the
      mandible: a technical note.
AB  - The following report refers to a well described surgical procedure using a
      prototype vertical distractor developed in Cologne in cooperation with Martin
      Medizintechnik GmbH. The surgical technique has been refined by an L-shaped
      osteotomy stabilized posteriorly by a miniplate to limit the amount of callus
      regeneration in the molar region where no increase in vertical height is
      required. The surgical technique with its advantages and one complication is
      described as used in four patients undergoing six distraction treatments.

PMID- 10964556
TI  - Gilbert's conjecture: the search for DNA (cytosine-5) demethylases and the
      emergence of new functions for eukaryotic DNA (cytosine-5) methyltransferases.
AB  - In 1985 Walter Gilbert challenged members of the DNA methylation community
      assembled at a National Institutes of Health meeting organized by Giulio Cantoni
      and Ahron Razin with the following words: "The most exciting aspect about the
      methyl groups on DNA is the thought that they might provide a locally inherited
      change in a DNA structure. However, for that to be interesting, those changes
      have to be different in different cells. Furthermore, the alterations in
      methylation have to be freely imposable and have to be maintained. It is not yet
      clear that all these properties are true. So I don't think one will find that
      methylation ever is one of the primary, top-level controls on gene expression."In
      essence, Gilbert's conjecture, that DNA methylation is not one of the top-level
      controls on gene expression, assumes that evidence in favor of both of its
      testable propositions will not be obtained. Evidence for the first proposition,
      that alterations in methylation status associated with gene-expression states
      have to be maintained, was already available in 1985 and has been strengthened by
      a number of very recent experiments. However, the extensive effort to obtain
      evidence for the second proposition, that alterations in methylation status be
      freely imposable, has not been successful in its original intent. The effort has,
      on the other hand, resulted in the emergence of new functions for 5
      methylcytosine and the cytosine methyltransferases in eukaryotic DNA repair,
      recombination and chromosome stability.

PMID- 10964557
TI  - Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8
      Z-DEVD-cho complex.
AB  - Caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the
      downstream executioner caspase-3 is a physiological target. Caspases are cysteine
      proteases that are specific for substrates with an aspartic acid residue at the
      P(1) position and have an optimal recognition motif that incorporates four amino
      acid residues N-terminal to the cleavage site. Caspase-8 has been classified as a
      group III caspase member because it shows a preference for a small hydrophobic
      residue at the P(4) substrate position. We report the X-ray crystallographic
      structure of caspase-8 in complex with benzyloxycarbonyl-Asp-Glu-Val-Asp-aldehyde
      (Z-DEVD), a specific group II caspase inhibitor. The structure shows that the
      inhibitor interacts favourably with the enzyme in subsite S(4). Kinetic data
      reveal that Z-DEVD (K(i) 2 nM) is an almost equally potent inhibitor of caspase-8
      as the specific group III inhibitor Boc-IETD-aldehyde (K(i) 1 nM). In view of
      this finding, the original classification of caspases into three specificity
      groups needs to be modified, at least for caspase-8, which tolerates small
      hydrophobic residues as well as the acidic residue Asp in subsite S(4). We
      propose that the subsite S(3) must be considered as an important specificity
      determining factor.

PMID- 10964558
TI  - Upstream flanking sequences and transcription of SINEs.
AB  - SINEs, short interspersed repeated DNA elements, undergo amplification through
      retroposition and subsequent integration into a new location in the genome. Each
      new SINE insertion will be located in a new chromosomal environment, with
      different flanking sequences. Modulation of transcription by different flanking
      sequences may play an important role in determining which SINE elements are
      preferentially active in a genome. We evaluated the ability of upstream flanking
      sequences to regulate the transcription of three different SINEs (Alu, B2 and ID)
      by constructing chimeric constructs with known 5' flanking sequences of RNA
      polymerase III-transcribed genes. Upstream sequences from the 7SL RNA gene, U6
      RNA gene, vault RNA gene, and BC1 gene increase transcription of Alu, B2 and BC1
      in transient transfections of NIH3T3, HeLa, Neuro2a and C6 glioma cell lines. The
      7SL sequence proved most efficient in increasing SINE transcription. The 7SL
      upstream fused to the BC1 RNA gene (an ID element) was used to create a
      transgenic mouse line. In contrast to the tissue-specific endogenous BC1
      transcription, BC1 transgene transcripts were detected in all tissues tested.
      However, expression was much higher in those tissues that express the endogenous
      gene, demonstrating both transcriptional and post-transcriptional regulation. The
      BC1 RNA was detected in a similar ribonucleoprotein complex in the different
      tissues.

PMID- 10964559
TI  - Chimeras of the Flp and Cre recombinases: tests of the mode of cleavage by Flp
      and Cre.
AB  - The Flp and Cre recombinases are members of the integrase family of tyrosine
      recombinases. Each protein consists of a 13 kDa NH(2)-terminal domain and a
      larger COOH-terminal domain that contains the active site of the enzyme. The COOH
      terminal domain also contains the major determinants for the binding specificity
      of the recombinase to its cognate DNA binding site. All family members cleave the
      DNA by the attachment of a conserved nucleophilic tyrosine residue to the 3'
      phosphate group at the sites of cleavage. In order to gain further insights into
      the determinants of the binding specificity and modes of cleavage of Flp and Cre,
      we have made chimeric proteins in which we have fused the NH(2)-terminal domain
      of Flp to the COOH-terminal domain of Cre ("Fre") and the NH(2)-terminal domain
      of Cre to the COOH-terminal domain of Flp ("Clp"). These chimeras have novel
      binding specificities in that they bind strongly to hybrid sites containing
      elements from both the Flp and Cre DNA targets but poorly to the native target
      sites. In this study we have taken advantage of the unique binding specificities
      of Fre and Clp to examine the mode of cleavage by Cre, Flp, Fre and Clp. We find
      that the COOH-terminal domain of the recombinases determines their mode of
      cleavage. Thus Flp and Clp cleave in trans whereas Cre and Fre cleave in cis.
      These results agree with the studies of Flp and with the cocrystal structure of
      Cre bound to its DNA target site. They disagree with our previous findings that
      Cre could carry out trans cleavage. We discuss the variations in the experimental
      approaches in order to reconcile the different results.

PMID- 10964560
TI  - Characterization of a Tn5 pre-cleavage synaptic complex.
AB  - Protein catalyzed DNA rearrangements typically require assembly of complex
      nucleoprotein structures. In transposition and integration reactions, these
      structures, termed synaptic complexes, are mandatory for catalysis. We
      characterize the Tn5 pre-cleavage synaptic complex, the simplest transposition
      complex described to date. We identified this complex by gel retardation assay
      using short, linear fragments and have shown that it contains a dimer of
      transposase, two DNA molecules, and is competent for DNA cleavage in the presence
      of Mg(2+). We also used hydroxyl radical footprinting and interference techniques
      to delineate the protein-DNA contacts made in the Tn5 synaptic and monomer
      complexes. All positions (except position 1) of the end sequence are contacted by
      transposase in the synaptic complex. We have determined that positions 2-5 of the
      end sequence are specifically required for synaptic complex formation as they are
      not required for monomer complex formation. In addition, in the synaptic complex,
      there is a strong, local distortion centered around position 1 which likely
      facilitates cleavage.

PMID- 10964561
TI  - Ribosomal RNA maturation in Schizosaccharomyces pombe is dependent on a large
      ribonucleoprotein complex of the internal transcribed spacer 1.
AB  - The interdependency of steps in the processing of pre-rRNA in Schizosaccharomyces
      pombe suggests that RNA processing, at least in part, acts as a quality control
      mechanism which helps assure that only functional RNA is incorporated into mature
      ribosomes. To determine further the role of the transcribed spacer regions in
      rRNA processing and to detect interactions which underlie the interdependencies,
      the ITS1 sequence was examined for its ability to form ribonucleoprotein
      complexes with cellular proteins. When incubated with protein extract, the spacer
      formed a specific large RNP. This complex was stable to fractionation by agarose
      or polyacrylamide gel electrophoresis. Modification exclusion analyses indicated
      that the proteins interact with a helical domain which is conserved in the
      internal transcribed spacers. Mutagenic analyses confirmed an interaction with
      this sequence and indicated that this domain is critical to the efficient
      maturation of the precursor RNA. The protein constituents, purified by affinity
      chromatography using the ITS1 sequence, retained an ability to form stable RNP.
      Protein analyses of gel purified complex, prepared with affinity-purified
      proteins, indicated at least 20 protein components ranging in size from 20-200
      kDa. Peptide mapping by Maldi-Toff mass spectroscopy identified eight
      hypothetical RNA binding proteins which included four different RNA-binding
      motifs. Another protein was putatively identified as a pseudouridylate synthase.
      Additional RNA constituents were not detected. The significance of this complex
      with respect to rRNA maturation and interdependence in rRNA processing is
      discussed.

PMID- 10964562
TI  - Stabilization of RNA tertiary structure by monovalent cations.
AB  - The effects of monovalent cations (Li(+), Na(+), K(+), Rb(+), Cs(+), and NH4(+))
      on the thermal stability of RNA tertiary structure were investigated by UV
      melting. We show that with the RNA used here (nucleotides 1051-1108 of
      Escherichia coli 23 S rRNA with four base substitutions), monovalent cations and
      Mg(2+) compete in stabilizing the RNA tertiary structure, and that the
      competition takes place between two boundaries: one where Mg(2+) concentration is
      zero and the other where it is maximally stabilizing ("saturating"). The pattern
      of competition is the same for all monovalent cations and depends on the cation's
      ability to displace Mg(2+) from the RNA, its ability to stabilize tertiary
      structure in the absence of Mg(2+), and its ability to stabilize tertiary
      structure at saturating Mg(2+) concentrations. The stabilizing ability of a
      monovalent cation depends on its unhydrated ionic radius, and at a low monovalent
      cation concentration and saturating Mg(2+), there is a (calculated) net release
      of a single monovalent cation/RNA molecule when tertiary structure is denatured.
      The implications are that under these conditions there is at least one binding
      site for monovalent cations on the RNA, the site is specifically associated with
      formation of stable tertiary structure, K(+) is the most effective of the tested
      cations, and Mg(2+) appears ineffective at this site. At high ionic strength, and
      in the absence of Mg(2+), stabilization of tertiary structure is still monovalent
      cation specific and ionic-radius dependent, but a larger number of cations (
      approximately eight) are released upon RNA tertiary structure denaturation, and
      NH(4)(+) appears to be the most effective cation in stabilizing tertiary
      structure under these conditions. In the majority of the experiments, methanol
      was added as a cosolvent to the buffer. Its use allowed the examination of the
      behavior of monovalent ions under conditions where their effects would otherwise
      have been too weak to be observed. Methanol stabilizes tertiary but not secondary
      structure of the RNA. There was no evidence that it either causes qualitative
      changes in cation-binding properties of the RNA or a change in the pattern of
      monovalent cation/Mg(2+) competition.

PMID- 10964563
TI  - Sleeping Beauty, a wide host-range transposon vector for genetic transformation
      in vertebrates.
AB  - Sleeping Beauty (SB), a member of the Tc1/mariner superfamily of transposable
      elements, is the only active DNA-based transposon system of vertebrate origin
      that is available for experimental manipulation. We have been using the SB
      element as a research tool to investigate some of the cis and trans-requirements
      of element mobilization, and mechanisms that regulate transposition in vertebrate
      species. In contrast to mariner transposons, which are regulated by
      overexpression inhibition, the frequency of SB transposition was found to be
      roughly proportional to the amount of transposase present in cells. Unlike Tc1
      and mariner elements, SB contains two binding sites within each of its terminal
      inverted repeats, and we found that the presence of both of these sites is a
      strict requirement for mobilization. In addition to the size of the transposon
      itself, the length as well as sequence of the DNA outside the transposon have
      significant effects on transposition. As a general rule, the closer the
      transposon ends are, the more efficient transposition is from a donor molecule.
      We have found that SB can transform a wide range of vertebrate cells from fish to
      human. However, the efficiency and precision of transposition varied
      significantly among cell lines, suggesting potential involvement of host factors
      in SB transposition. A positive-negative selection assay was devised to enrich
      populations of cells harboring inserted transposons in their chromosomes. Using
      this assay, of the order of 10,000 independent transposon insertions can be
      generated in human cells in a single transfection experiment. Sleeping Beauty can
      be a powerful alternative to other vectors that are currently used for the
      production of transgenic animals and for human gene therapy.

PMID- 10964564
TI  - The Saccharomyces cerevisiae homologue YPA1 of the mammalian phosphotyrosyl
      phosphatase activator of protein phosphatase 2A controls progression through the
      G1 phase of the yeast cell cycle.
AB  - The Saccharomyces cerevisiae gene YPA1 encodes a protein homologous to the
      phosphotyrosyl phosphatase activator, PTPA, of the mammalian protein phosphatase
      type 2A (PP2A). In order to examine the biological role of PTPA, we disrupted
      YPA1 and characterised the phenotype of the ypa1Delta mutant. Comparison of the
      growth rate of the wild-type strain and the ypa1Delta mutant on glucose-rich
      medium after nutrient depletion showed that the ypa1Delta mutant traversed the
      lag period more rapidly. This accelerated progression through "Start" was also
      observed after release from alpha-factor-induced G1 arrest as evidenced by a
      higher number of budding cells, a faster increase in CLN2 mRNA expression and a
      more rapid reactivation of Cdc28 kinase activity. This phenotype was specific for
      deletion of YPA1 since it was not observed when YPA2, the second PTPA gene in
      budding yeast was deleted. Reintroduction of YPA1 or the human PTPA cDNA in the
      ypa1Delta mutant suppressed this phenotype as opposed to overexpression of YPA2.
      Disruption of both YPA genes is lethal, since sporulation of heterozygous
      diploids resulted in at most three viable spores, none of them with a ypa1Delta
      ypa2Delta genotype. This observation indicates that YPA1 and YPA2 share some
      essential functions. We compared the ypa1Delta mutant phenotype with a PP2A
      double deletion mutant and a PP2A temperature-sensitive mutant. The PP2A
      deficient yeast strain also showed accelerated progression through the G1 phase.
      In addition, both PP2A and ypa1Delta mutants show similar aberrant bud
      morphology. This would support the notion that YPA1 may act as a positive
      regulator of PP2A in vivo.

PMID- 10964565
TI  - Three-dimensional organization of retroviral capsid proteins on a lipid
      monolayer.
AB  - We have used a method for the two-dimensional crystallization of retroviral
      structural proteins to obtain a three-dimensional structure of negatively
      stained, membrane-bound, histidine-tagged Moloney murine leukemia virus (M-MuLV)
      capsid protein (his-MoCA) arrays. Tilted and untilted micrographs from crystals
      formed by purified his-MoCA proteins incubated beneath lipid monolayers
      containing nickel-chelating lipids were used in 3D reconstructions. The 2D
      crystals had unit cell dimensions of a=72.6 A, b=72.5 A and gamma=119.5 degrees,
      but appeared to have no intrinsic symmetry (p1) in 3D, in contrast to the
      trigonal or hexagonal appearance of their 2D projections. Membrane-bound his-MoCA
      proteins showed a strand-like organization, apparently with dimer building
      blocks. Membrane-proximal regions, or putative N-terminal domains (NTDs),
      dimerized with different partners than the membrane-distal putative C-terminal
      domains (CTDs). Evidence also suggests that CTDs can adopt alternate orientations
      relative to their NTDs, forming interstrand connections. Our results are
      consistent with helical-spiral models for retrovirus particle assembly, but are
      not easily reconcilable with icosahedral models.

PMID- 10964566
TI  - Crystal structures of two functionally different thioredoxins in spinach
      chloroplasts.
AB  - Thioredoxins are small ubiquitous proteins which act as general protein disulfide
      reductases in living cells. Chloroplasts contain two distinct thioredoxins ( f
      and m) with different phylogenetic origin. Both act as enzyme regulatory proteins
      but have different specificities towards target enzymes. Thioredoxin f (Trx f),
      which shares only low sequence identity with thioredoxin m (Trx m) and with all
      other known thioredoxins, activates enzymes of the Calvin cycle and other
      photosynthetic processes. Trx m shows high sequence similarity with bacterial
      thioredoxins and activates other chloroplast enzymes. The here described
      structural studies of the two chloroplast thioredoxins were carried out in order
      to gain insight into the structure/function relationships of these proteins.
      Crystal structures were determined for oxidized, recombinant thioredoxin f (Trx f
      L) and at the N terminus truncated form of it (Trx f-S), as well as for oxidized
      and reduced thioredoxin m (at 2.1 and 2.3 A resolution, respectively). Whereas
      thioredoxin f crystallized as a monomer, both truncated thioredoxin f and
      thioredoxin m crystallized as non-covalent dimers. The structures of thioredoxins
      f and m exhibit the typical thioredoxin fold consisting of a central twisted five
      stranded beta-sheet surrounded by four alpha-helices. Thioredoxin f contains an
      additional alpha-helix at the N terminus and an exposed third cysteine close to
      the active site. The overall three-dimensional structures of the two chloroplast
      thioredoxins are quite similar. However, the two proteins have a significantly
      different surface topology and charge distribution around the active site. An
      interesting feature which might significantly contribute to the specificity of
      thioredoxin f is an inherent flexibility of its active site, which has expressed
      itself crystallographically in two different crystal forms.

PMID- 10964567
TI  - Structural basis for isotype selectivity of the human retinoic acid nuclear
      receptor.
AB  - The human retinoic acid receptor (hRAR) belongs to the family of nuclear
      receptors that regulate transcription in a ligand-dependent way. The isotypes
      RARalpha,beta and gamma are distinct pharmacological targets for retinoids that
      are involved in the treatment of various skin diseases and cancers, in particular
      breast cancer and acute promyelocytic leukemia. Therefore, synthetic retinoids
      have been developed aiming at isotype selectivity and reduced side-effects. We
      report the crystal structures of three complexes of the hRARgamma ligand-binding
      domain (LBD) bound to agonist retinoids that possess selectivity either for
      RARgamma (BMS184394) or for RARbeta/gamma (CD564), or that are potent for all RAR
      isotypes (panagonist BMS181156). The high resolution data (1.3-1. 5 A) provide a
      description at the atomic level of the ligand pocket revealing the molecular
      determinants for the different degrees of ligand selectivity. The comparison of
      the complexes of the chemically closely related retinoids BMS184394 and CD564
      shows that the side-chain of Met272 adopts different conformations depending on
      the presence of a hydrogen bond between its sulfur atom and the ligand. This
      accounts for their different isotype selectivity. On the other hand, the
      difference between the pan- and the RARbeta, gamma-selective agonist is probably
      due to a steric discrimination at the level of the 2-naphthoic acid moiety of
      CD564. Based on this study, we propose a model for a complex with the RARgamma
      specific agonist CD666 that shows the possible applications for structure-based
      drug design of RAR isotype-selective retinoids.

PMID- 10964568
TI  - The three-dimensional solution structure and dynamic properties of the human FADD
      death domain.
AB  - FADD (also known as MORT-1) is an essential adapter protein that couples the
      transmembrane receptors Fas (CD95) and tumor necrosis factor receptor-1 (TNF-R1)
      to intracellular cysteine proteases known as caspases, which propagate and
      execute the programmed cell death-inducing signal triggered by Fas ligand (FasL,
      CD95L) and TNF. FADD contains 208 amino acid residues, and comprises two
      functionally and structurally distinct domains: an N-terminal death effector
      domain (DED) that promotes activation of the downstream proteolytic cascade
      through binding of the DED domains of procaspase-8; and a C-terminal death domain
      (DD). FADD-DD provides the site of FADD recruitment to death receptor complexes
      at the plasma membrane by, for example, interaction with the Fas receptor
      cytoplasmic death domain (Fas-DD), or binding of the TNF-R1 adapter molecule
      TRADD. We have determined the three-dimensional solution structure and
      characterised the internal polypeptide dynamics of human FADD-DD using
      heteronuclear NMR spectroscopy of (15)N and (13)C,(15)N-labelled samples. The
      structure comprises six alpha-helices joined by short loops and displays overall
      similarity to the death domain of the Fas receptor. The analysis of the dynamic
      properties reveals no evidence of contiguous stretches of polypeptide chain with
      increased internal motion, except at the extreme chain termini. A pattern of
      increased rates of amide proton solvent exchange in the alpha3 helix correlates
      with a higher degree of solvent exposure for this secondary structure element.
      The properties of the FADD-DD structure are discussed with respect to previously
      reported mutagenesis data and emerging models for FasL-induced FADD recruitment
      to Fas and caspase-8 activation.

PMID- 10964570
TI  - T-Coffee: A novel method for fast and accurate multiple sequence alignment.
AB  - We describe a new method (T-Coffee) for multiple sequence alignment that provides
      a dramatic improvement in accuracy with a modest sacrifice in speed as compared
      to the most commonly used alternatives. The method is broadly based on the
      popular progressive approach to multiple alignment but avoids the most serious
      pitfalls caused by the greedy nature of this algorithm. With T-Coffee we pre
      process a data set of all pair-wise alignments between the sequences. This
      provides us with a library of alignment information that can be used to guide the
      progressive alignment. Intermediate alignments are then based not only on the
      sequences to be aligned next but also on how all of the sequences align with each
      other. This alignment information can be derived from heterogeneous sources such
      as a mixture of alignment programs and/or structure superposition. Here, we
      illustrate the power of the approach by using a combination of local and global
      pair-wise alignments to generate the library. The resulting alignments are
      significantly more reliable, as determined by comparison with a set of 141 test
      cases, than any of the popular alternatives that we tried. The improvement,
      especially clear with the more difficult test cases, is always visible,
      regardless of the phylogenetic spread of the sequences in the tests.

PMID- 10964569
TI  - Structure-based functional classification of hypothetical protein MTH538 from
      Methanobacterium thermoautotrophicum.
AB  - The structure of MTH538, a previously uncharacterized hypothetical protein from
      Methanobacterium thermoautotrophicum, has been determined by NMR spectroscopy.
      MTH538 is one of numerous structural genomics targets selected in a genome-wide
      survey of uncharacterized sequences from this organism. MTH538 is a so-called
      singleton, a sequence not closely related to any other (known) sequences. The
      structure of MTH538 closely resembles the known structures of receiver domains
      from two component response regulator systems, such as CheY, and is similar to
      the structures of flavodoxins and GTP-binding proteins. Tests on MTH538 for
      characteristic activities of CheY and flavodoxin were negative. MTH538 did not
      become phosphorylated in the presence of acetyl phosphate and Mg(2+), although it
      appeared to bind Mg(2+). MTH538 also did not bind flavin mononucleotide (FMN) or
      coenzyme F(420). Nevertheless, sequence and structure parallels between
      MTH538/CheY and two families of ATPase/phosphatase proteins suggest that MTH538
      may have a role in a phosphorylation-independent two-component response regulator
      system.

PMID- 10964571
TI  - Conversion of two-state to multi-state folding kinetics on fusion of two protein
      foldons.
AB  - Chymotrypsin inhibitor 2 (CI2) is the archetypal single-foldon protein that folds
      in simple two-state kinetics without the accumulation of a folding intermediate.
      To model the effects of fusion of single foldons to give a multi-foldon protein,
      we engineered a "double-CI2" protein, in which another CI2 polypeptide was
      inserted into the loop region of the parent CI2. CD and HSQC spectra demonstrated
      that while the double-CI2 protein adopted two kinds of native conformations, CI2
      like structure was almost preserved in both the domains of double-CI2. In the
      folding kinetic studies, double-CI2 exhibited a remarkable rollover of the
      observed folding rates at low denaturant concentrations, indicating that double
      CI2 accumulated a kinetic folding intermediate. The different folding mechanisms
      between WT-CI2 and double-CI2 support the present view that protein size or
      number of domains is an important determinant for formation of folding
      intermediates.

PMID- 10964572
TI  - Complementation between dimeric mutants as a probe of dimer-dimer interactions in
      tetrameric dihydrofolate reductase encoded by R67 plasmid of E. coli.
AB  - The effect of mutations on the interactions between dimers in R67 dihydrofolate
      reductase (R67 DHFR), a tetrameric enzyme conferring resistance to trimethoprim,
      was investigated by site-directed mutagenesis combined with phenotypic,
      enzymatic, and biochemical analysis. Some 14 mutants at two positions involved in
      a hydrogen bond between dimers were constructed. All were shown to be dimers.
      However, complementation between pairs of dimeric mutated proteins resulted in
      the restoration of the enzymatic activity and heterotetramer formation. A
      combinatorial approach was set up to create efficiently such heterotetramers and
      identify the complementing pairs of mutations. A dozen of such pairs were found.
      An accurate method was set up to measure the association of the complementing
      dimers in a "quasi-isologous" heterotetramer and used to study the effects of
      mutations and pH on the association. Thus, the pair of proteins bearing
      respectively the S59A and H62L mutations was shown to form heterotetramers with
      catalytic properties close to those of the wild-type protein. Its association was
      as strong as that of the wild-type protein at cytoplasmic pH (6. 5), and was more
      stable at lower pH values.A double-mutant protein bearing simultaneously the S59A
      and H62L mutations was produced and analyzed. Its association was weakened by 1.2
      kcal/mol as compared to the wild-type enzyme at pH 6.5 but was insensitive to pH.
      Comparing the energy of association between dimers in the wild-type protein, the
      heterotetramer and the double mutant allowed us to dissect the effects of the pH
      and of the molecular context on a subset of interactions between the R67 DHFR
      subunits.

PMID- 10964573
TI  - The adoption of a twisted structure of importin-beta is essential for the protein
      protein interaction required for nuclear transport.
AB  - Importin-beta is a nuclear transport factor which mediates the nuclear import of
      various nuclear proteins. The N-terminal 1-449 residue fragment of mouse importin
      beta (impbeta449) possesses the ability to bidirectionally translocate through
      the nuclear pore complex (NPC), and to bind RanGTP. The structure of the
      uncomplexed form of impbeta449 has been solved at a 2.6 A resolution by X-ray
      crystallography. It consists of ten copies of the tandemly arrayed HEAT repeat
      and exhibits conformational flexibility which is involved in protein-protein
      interaction for nuclear transport. The overall conformation of the HEAT repeats
      shows that a twisted motion produces a significantly varied superhelical
      architecture from the previously reported structure of RanGTP-bound importin
      beta. These conformational changes appear to be the sum of small conformational
      changes throughout the polypeptide. Such a flexibility, which resides in the
      stacked HEAT repeats, is essential for interaction with RanGTP or with NPCs.
      Furthermore, it was found that impbeta449 has a structural similarity with
      another nuclear migrating protein, namely beta-catenin, which is composed of
      another type of helix-repeated structure of ARM repeat. Interestingly, the
      essential regions for NPC translocation for both importin-beta and beta-catenin
      are spatially well overlapped with one another. This strongly indicates the
      importance of helix stacking of the HEAT or ARM repeats for NPC-passage.

PMID- 10964574
TI  - Statistical alignment: computational properties, homology testing and goodness-of
      fit.
AB  - The model of insertions and deletions in biological sequences, first formulated
      by Thorne, Kishino, and Felsenstein in 1991 (the TKF91 model), provides a basis
      for performing alignment within a statistical framework. Here we investigate this
      model.Firstly, we show how to accelerate the statistical alignment algorithms
      several orders of magnitude. The main innovations are to confine likelihood
      calculations to a band close to the similarity based alignment, to get good
      initial guesses of the evolutionary parameters and to apply an efficient
      numerical optimisation algorithm for finding the maximum likelihood estimate. In
      addition, the recursions originally presented by Thorne, Kishino and Felsenstein
      can be simplified. Two proteins, about 1500 amino acids long, can be analysed
      with this method in less than five seconds on a fast desktop computer, which
      makes this method practical for actual data analysis.Secondly, we propose a new
      homology test based on this model, where homology means that an ancestor to a
      sequence pair can be found finitely far back in time. This test has statistical
      advantages relative to the traditional shuffle test for proteins.Finally, we
      describe a goodness-of-fit test, that allows testing the proposed insertion
      deletion (indel) process inherent to this model and find that real sequences
      (here globins) probably experience indels longer than one, contrary to what is
      assumed by the model.

PMID- 10964575
TI  - Fundamental computations in neural systems.

PMID- 10964576
TI  - Image processing techniques applied to excitation waves in the chicken retina.
AB  - Image processing techniques are described in detail that are used to gain
      information about the dynamics of wave propagation in excitable media. We focus
      on a phenomenon called spreading depression (SD) observed in the chicken retina,
      but the techniques described here concern a large variety of excitable systems.
      Despite the impressive progress both in SD research of the past 50 years and,
      during nearly the same period, in the theory of self-organization of wave
      patterns, there is still little mutual overlap. However, the increasing demands
      for understanding complex systems, like neuronal tissue, require such theoretical
      concepts. Arguments are given why the chicken retina is a nearly perfect
      experimental system for assessing and further developing these concepts.

PMID- 10964577
TI  - High-speed digital microscopy.
AB  - High-speed imaging is an ideal technique to accurately resolve the temporal and
      spatial characteristics of rapid events at either the molecular or cellular
      level. In this article, the digital imaging techniques used to simultaneously
      acquire transillumination phase-contrast images, at 240 images s(-1) (high
      speed), to characterize ciliary beat frequency, and fluorescence images, at 30
      images s(-1) (fast), to measure intracellular calcium concentration ([Ca2+]i),
      are described. With this technique, a precise correlation between the changes in
      ciliary beat frequency with changes in [Ca2+]i can be made. Simultaneous imaging
      is achieved by using different wavelengths of light to form the phase-contrast
      and fluorescent images and selectively directing these light wavelengths to
      different cameras with dichroic mirrors and bandpass filters. High-speed images
      compatible with standard video recording equipment are obtained by prematurely
      resetting the raster scan of a CCD camera with additional vertical
      synchronization pulses. The fast [Ca2+]i images are determined using the
      ratiometric dye fura-2 and a recording technique that monitors rapid changes in
      fluorescence at a single wavelength and uses intermittent reference images for
      calibration.

PMID- 10964578
TI  - Dual video microscopic imaging of membrane potential and cytosolic calcium of
      immunoidentified embryonic rat cortical cells.
AB  - Membrane potential (MP) and cytosolic Ca2+ (Ca2+(c)) constitute important
      components involved in the physiological regulation of a myriad of cell functions
      in eukaryotic organisms. In particular, during development of the central nervous
      system, both properties are thought to be important in the regulation of cell
      cycle, cell migration, cell differentiation, cell-cell communication, and
      naturally occurring cell death. However, obtaining insight into the precise
      relationship between these two parameters of cell function is relatively limited
      either by technical difficulties inherent in using electrical recordings of
      membrane properties in conjunction with optical imaging of single cells or by
      employing optical imaging of either one or another property alone. Here, we
      describe in detail a novel strategy to record changes in both MP and Ca2+(c) from
      many intact single cells in a noninvasive manner using digital video microscopy.
      This method involves double-loading the cells with voltage- and calcium-sensitive
      fluorescent indicator dyes, green oxonol, and fura-2, which can be sequentially
      excited with a mercury arc lamp filtered at appropriate wavelengths and their
      resulting emissions can be captured with an intensified charged-coupled device
      camera at 1-s intervals. As an example of the utility of dual-recording strategy,
      we present data on a distinct functional expression of excitable membrane and
      cytoplasmic calcium properties in proliferating and differentiating embryonic rat
      cerebral cortical cells.

PMID- 10964579
TI  - High-definition mapping of neural activity using voltage-sensitive dyes.
AB  - The distribution of patterns of activity in different brain structures has been
      related to the encoding and processing of sensory information. Consequently, it
      is important to be able to image the distribution of these patterns to understand
      basic brain functions. The spatial resolution of voltage-sensitive dye (VSD)
      methods has recently been enhanced considerably by the use of video imaging
      techniques. The main factor that now hampers the resolution of VSD patterns is
      the inherent limitation of the optical systems. Unfortunately, the intrinsic
      characteristics of VSD images impose important limitations that restrict the use
      of general deconvolution techniques. To overcomes this problem, in this study an
      image restoration procedure has been implemented that takes into consideration
      the limiting characteristics of VSD signals. This technique is based on applying
      a set of imaging processing steps. First, the signal-to-noise (S/N) ratio of the
      images was improved to avoid an increase in the noise levels during the
      deconvolution procedures. For this purpose, a new filter technique was
      implemented that yielded better results than other methods currently used in
      optical imaging. Second, focal plane images were deconvolved using a modification
      of the well-known nearest-neighbor deconvolution algorithm. But to reduce the
      light exposure of the preparation and simplify image acquisition procedures,
      adjacent image planes were modeled according to the in-focus image planes and the
      empirical point spread function (PSF) profiles. Third, resulting focal plane
      responses were processed to reduce the contribution of optical responses that
      originate in distant image planes. This method was found to be satisfactory under
      simulated and real experimental conditions. By comparing the restored and
      unprocessed images, it was clearly demonstrated that this method can effectively
      remove the out-of-focus artifacts and produce focal plane images of better
      quality. Evaluations of the tissue optical properties allowed assessment of the
      maximum practical optical section thickness using this deconvolution technique in
      the optical system tested. Determination of the three-dimensional PSF permitted
      the correct application of deconvolution algorithms and the removal of the
      contaminating light arising from adjacent as well as distant optical planes. The
      implementation of this deconvolution approach in salamander olfactory bulb
      allowed the detailed study of the laminar distribution of voltage-sensitive
      changes across the bulb layer. It is concluded that (1) this deconvolution
      procedure is well suited to deconvolved low-contrast images and offers important
      advantages over other alternatives; (2) this method can be properly used only
      when the tissue optical properties are first determined; (3) high levels of light
      scattering in the tissue reduce the optical section capabilities of this
      technique as well as other deconvolution procedures; and (4) use of the highest
      numerical aperture in the objectives is advisable because this improves not only
      the light-collecting efficiency to detect poor-contrast images, but also the
      spatial frequency differences between adjacent image planes. Under this condition
      it is possible to overcome some of the limitations imposed by the light
      scattering/birefringence of the tissue.

PMID- 10964580
TI  - Simultaneous intracellular recording and calcium imaging in single neurons of
      hippocampal slices.
AB  - Fluorescent Ca2+ indicator dyes can be introduced into cells through the same
      microelectrode used for intracellular voltage recording. Simultaneous measurement
      of cell membrane potential and intracellular Ca2+ concentration can be very
      helpful in interpreting the mechanisms of Ca2+ increases. This chapter describes
      fluorescence image acquisition using a CCD camera and a computer program that
      also records a synchronized membrane potential trace. The same program allows for
      preliminary data analysis. More elaborate analyses can be accomplished with
      commercial programs. We also describe quantitative evaluations of sources of
      error in the use of the statistic deltaF/F as an indicator of Ca2+ concentration.
      Especially important errors to minimize are changes in background fluorescence
      and inappropriate autofluorescence corrections. Some improvement of fluorescence
      images of cells deep within slices may be accomplished by masking. One method is
      described for making a mask based on the raw fluorescence image. With another
      method, highly detailed cell morphologies may be conveyed by using masks based on
      neurobiotin injections and camera lucida drawings.

PMID- 10964581
TI  - Applications of video mixing and digital overlay to neuroethology.
AB  - Neuroethological experiments often require video images of animal behavior and
      recordings of physiological data to be acquired simultaneously, synchronized with
      each other, stored, and analyzed together. The use of inexpensive multimedia
      computers offers new possibilities for mixing video images, analog voltages, and
      computer data, storing these combined signals to videotape, and extracting
      quantitative data for analysis. In this paper, we summarize methods for mixing
      images from multiple video cameras and a Macintosh computer display to facilitate
      manipulation of data generated during our neurophysiological and behavioral
      research. These technologies enhance accuracy, speed, and flexibility during
      experiments, and facilitate selecting and extracting quantitative data from the
      videotape for further analysis. Three applications are presented: (A) we used an
      analog video mixer to synchronize neurophysiological recordings with ongoing
      behaviors of freely moving rats; (B) we used a chroma keyed digital overlay to
      generate positional data for the rat's face during drinking behavior; and (C) we
      combined a computer model of a rat's head and whiskers with videos of exploratory
      behaviors to better track and quantify movements in three dimensions. Although
      the applications described here are specific to our neuroethological work, these
      methods will be useful to anyone wishing to combine the signals from multiple
      video sources into a single image or to extract series of positional or movement
      data from video frames without frame grabbing.

PMID- 10964582
TI  - Each administration of cyclosporin A enhances skin microvascular reactivity in
      renal transplant recipients.
AB  - Both impaired and enhanced microvascular function have been described in humans
      on cyclosporin A (CsA) therapy. In the present study we investigated the acute
      microvascular effects of a single CsA administration in renal transplant
      recipients on maintenance CsA therapy. Fourteen renal transplant recipients,
      median age 48 years (range 24-63 years), transplanted 4-12 weeks earlier, were
      included in this placebo-controlled, double-blinded, crossover study. All
      recipients had stable renal function; median serum creatinine was 116 micromol/L
      (range 80-184 micromol/L). Immunosuppressive therapy consisted of CsA,
      prednisolone, and either azathioprine or mycophenolate. Microvascular function
      was assessed by laser Doppler flowmetry in combination with acetylcholine
      (endothelium dependent) stimulation and the postocclusive reactive hyperemia
      test. Measurements were performed before (control) and 2.5 h following
      administration of CsA (Neoral) or matching placebo and repeated with reversed
      medication after at least 6 days. Vasodilative responses to acetylcholine
      stimulation were significantly higher following CsA ingestion compared with
      placebo. The mean change in AUC(1.5) (area under the flux versus time curve) from
      control to 2.5 h was 100 +/-145 for CsA and -292 +/- 140 AU x min for placebo (P
      = 0.047, n = 10). The postocclusive hyperemic response AUC(rh) was also
      significantly higher following CsA intake (39 +/- 4 AU x min) compared to placebo
      (30 +/- 4 AU x min) (P = 0.006, n = 12). This study shows that each dose of CsA
      induces a transient increase in skin microvascular reactivity in renal transplant
      recipients. We speculate that this might be due to the potentiation of one or
      several endothelial-dependent compensatory vasodilative mechanisms in the
      microvascular bed.

PMID- 10964583
TI  - Notch4 and Jagged-1 induce microvessel differentiation of rat brain endothelial
      cells.
AB  - The mouse Notch4 gene is expressed specifically in endothelial cells. Notch4/int
      3, a truncated form of Notch4, acts as a constitutive activated Notch receptor.
      We used rat brain microvessel endothelial cells (RBE4) to study the role of
      Notch4 and Jagged-1 in endothelial cell differentiation. Both Notch4/int-3 and
      Jagged-1 were able to induce microvessel-like structures with morphological and
      biochemical properties similar to brain endothelial microvessels. Ectopic
      expression of full-length Notch4 did not effect RBE4 cells. Activation of the
      Notch signal transduction pathway was measured by the induction of endogenous
      Notch4 and Jagged-1 genes and of Jagged-1 proteins. The observed morphological
      changes to RBE4 cells correlated with endogenous Notch4 and Jagged-1 gene
      activation. Our observations demonstrate that Notch signaling can promote
      endothelial cell differentiation and morphogenesis.

PMID- 10964584
TI  - Stimulation of NO production and of eNOS phosphorylation in the microcirculation
      in vivo.
AB  - The role of nitric oxide (NO) in microvascular permeability is controversial, in
      part because the regulation of its endothelial constitutive synthase, eNOS, has
      been studied in vitro but not in vivo. Our study was designed to detect the
      morphologic and functional presence of eNOS and to test whether eNOS could be
      phosphorylated by platelet-activating factor (PAF), an agent that induces
      hyperpermeability. Immunocytochemistry was applied using human anti-eNOS
      antibodies in the hamster cheek pouch (hcp). The hcp microvessels demonstrated
      positive reaction products in the endothelium. The functional presence of eNOS in
      hcp was investigated by topical application of 10(-7) M PAF to the hcp and by
      measuring NO production by chemiluminescence. The mean baseline value of NO
      release was 63.3 +/- 6.9 pmol/ml (mean +/- SE). Application of PAF led to an
      increase in mean NO release to 120.8 +/- 31.2 pmol/ml (P < 0.05). In another
      series of experiments, 10(-7) M PAF was applied topically to hcp preincubated
      with [(32)P]orthophosphoric acid. Immunoprecipitation and Western blots detected
      (32)P-labeled bands that migrated with the mobility of positive eNOS indicating
      phosphorylated eNOS protein. The intensity of the radioactive bands was evaluated
      by computer-assisted image analysis. Comparison of the net band intensities
      yielded a mean PAF-treated/control ratio of 1.6 +/- 0.1. Our data demonstrate the
      morphologic and functional presence of eNOS in the microcirculation. The data
      also provide evidence that the function of microvascular eNOS is subject to
      regulation by phosphorylation.

PMID- 10964585
TI  - Retinoic acid selectively inhibits the vascular permeabilizing effect of
      VPF/VEGF, an early step in the angiogenic cascade.
AB  - All-trans-retinoic acid (RA) and other retinoids modulate cell growth and
      differentiation, generally favoring terminal cell differentiation and inhibiting
      carcinogenesis. Retinoids are also reported to inhibit angiogenesis and
      endothelial cell migration, actions that are also anti-carcinogenic. Vascular
      permeability factor/vascular endothelial growth factor (VPF/VEGF) is a
      multifunctional cytokine secreted by many tumors. It renders microvessels
      hyperpermeable to plasma and stimulates endothelial cell migration and division.
      To investigate further the mechanisms by which RA inhibits angiogenesis, we
      evaluated the effects of RA on VPF/VEGF-induced angiogenesis and microvascular
      permeability. RA selectively inhibited the angiogenic response induced by
      VPF/VEGF, but not that induced by fibroblast growth factor-2 (FGF-2), in the CAM
      assay. RA and two of its isomers also inhibited the vascular permeabilizing
      effect of VPF/VEGF but not that induced by histamine. The vascular
      permeabilization induced by VPF/VEGF and blocked by RA takes place within 1-15
      min, too short a time frame for RA to act by modulating transcription through
      classic retinoid receptors. RA also inhibited VPF/VEGF-induced phosphorylation of
      PLC-gamma and synthesis of cGMP but actually increased VPF/VEGF binding to
      cultured endothelial cells. Taken together, these findings indicate that RA
      selectively blocks VPF/VEGF-induced microvascular permeability and angiogenesis
      and also identify VPF/VEGF as a major target of RA action. The selectivity of
      RA's action suggests that other, RA-independent pathways must exist for the
      angiogenesis induced by FGF-2 and the vascular permeabilizing effect of
      histamine.

PMID- 10964587
TI  - Pulmonary microvascular changes during sepsis: evaluation using intravital
      videomicroscopy.
AB  - A variety of pulmonary microvascular changes occur during sepsis. These include
      abnormal vascular reactivity, leukocyte sequestration, and leakage of protein
      into the alveoli. Based on intravital videomicroscopy we have developed a method
      to directly assess in vivo the changes that occur in the pulmonary
      microcirculation in a rat model of sepsis. Male Sprague-Dawley rats were assigned
      to control or sepsis groups. Sepsis was induced by cecal ligation and
      perforation. Twenty four hours later, rats were anesthetized, mechanically
      ventilated, and their lung prepared for intravital videomicroscopy. A specially
      designed transparent thoracic window was inserted into the chest wall. The
      dependent surface of the lung was superfused with saline solution and visualized
      with an inverted microscope. Vascular contractility, to phenylephrine, (PE) and
      hypoxia of small (15-25 microm in diameter) and medium (40-50 microm) arterioles
      was examined. Leukocyte traffic in the pulmonary microcirculation was studied
      after in vivo labeling of leukocytes with Rhodamine and visualized with
      fluorescence microscopy. Leak of albumin into the alveolar space was measured
      with FITC-labeled albumin and fluorescence microscopy. Both small and medium
      sized pulmonary arterioles in septic animals exhibited attenuated vascular
      contractility to phenylephrine, but only medium-sized arterioles displayed
      hypocontractility to hypoxia. Further, in septic animals there was an increase in
      both the number of stationary leukocytes in the pulmonary microcirculation and an
      increase in alveolar capillary protein leak. We conclude: (1) direct
      visualization of the pulmonary microvascular pressor response to hypoxia and PE
      in the rat is possible using this technique, (2) similar to previous in vitro
      studies with larger vessels, pulmonary arterioles have an attenuated contractile
      response to PE and hypoxia in sepsis, and (3) there is an increase in both the
      number of stationary leukocytes and protein leak into the alveolus in the lungs
      of septic animals.

PMID- 10964586
TI  - Morphine attenuates leukocyte/endothelial interactions.
AB  - Gram-negative sepsis and subsequent endotoxic shock after surgery remain
      problematic in the United States and throughout the world. While morphine is
      widely prescribed for postoperative trauma pain management, there are reports
      that morphine may compromise the immune system and contribute to postoperative
      sepsis. The current study tested the hypothesis that morphine attenuates
      leukocyte rolling and sticking in both arterioles and venules via nitric oxide
      production. Nude mice implanted with slow-release morphine pellets were used in
      this study. The dorsal skinfold chamber model for intravital fluorescence
      microscopy on awake mice was used. Leukocyte/endothelial interactions were
      evaluated after bolus injection of oxidized low density lipoprotein. Morphine was
      found to significantly attenuate leukocyte rolling and sticking in both the
      arterial and venular side of the microcirculation. This attenuation was reversed
      by simultaneous implantation of naloxone pellets. The mechanisms of this
      attenuation were further investigated by administration of the nitric oxide
      synthase inhibitors NG-nitro-l-arginine (NOLA) and aminoguanidine (AG) in
      drinking water. NOLA was found to significantly reverse this morphine-induced
      attenuation of leukocyte rolling and sticking in both arterioles and venules.
      However, AG did not have the same effect. The results indicate that morphine
      interferes with leukocyte/endothelial cell interactions via stimulation of nitric
      oxide production.

PMID- 10964588
TI  - Use of wavelets to accurately determine parameters of laser Doppler reactive
      hyperemia.
AB  - Laser Doppler flowmetry (LDF) is a noninvasive method to monitor skin perfusion
      and is very useful in studying reactive hyperemia signals. For this latter case,
      the determination of peak flow (pLDF) and time to peak flow (tpLDF) is of great
      interest in discriminating between subjects with peripheral arterial obliterative
      diseases and those who are healthy. However, the myogenic mechanism provokes
      marked oscillations on all LDF signals. Therefore, an accurate detection of the
      parameters is very difficult. The present study shows that wavelets are a
      powerful tool to overcome this drawback. Six different processes using several
      wavelets are tested on 44 signals recorded on 11 healthy volunteers. The results
      prove that thresholding coefficients of a multilevel wavelet decomposition does
      not allow a valuable computation of the parameters but that the reconstruction of
      the approximation branch is an efficient method to accurately determine pLDF and
      tpLDF. Using this latter method, mean results for a 3-min occlusion give pLDF =
      46.80 a.u. and tpLDF = 17. 08 s. For a 2-min occlusion, pLDF and tpLDF are 39.19
      a.u. and 11.63 s, respectively. For a 1-min occlusion, the results give pLDF =
      36. 01 a.u., tpLDF = 8.48 s. Eventually, for a 30-s occlusion they give pLDF =
      33.86 a.u. and tpLDF = 5.60 s. These results can now be compared with those
      obtained on pathological subjects.

PMID- 10964589
TI  - Formation and actions of cyclic ADP-ribose in renal microvessels.
AB  - Recent studies indicated that cyclic ADP-ribose (cADPR) serves as a second
      messenger for intracellular Ca(2+) mobilization in a variety of mammalian cells.
      However, the metabolism and actions of cADPR in the renal vasculature are poorly
      understood. In the present study, we characterized the enzymatic pathway of the
      production and metabolism of cADPR along the renal vascular tree and determined
      the role of cADPR in the control of intracellular [Ca(2+)] and vascular tone. The
      high performance liquid chromatographic analyses showed that cADPR was produced
      and hydrolyzed along the renal vasculature. The maximal conversion rate of
      nicotinamide guanine dinucleotide (NGD) into cyclic GDP-ribose (that represents
      ADP-ribosyl cyclase activity for cADPR formation) was 8.69 +/- 2.39 nmol/min/mg
      protein in bulk-dissected intrarenal preglomerular vessels (n = 7) and 4.35 +/-
      0.13, 2.23 +/- 0.27, 2.40 +/- 0.19, and 0.31 +/- 0.02 nmol/min/mg protein,
      respectively, in microdissected arcuate arteries (n = 6), interlobular arteries
      (n = 6), afferent arterioles (n = 7), and vasa recta (n = 10). The activity of
      cADPR hydrolase was also detected in the renal vasculature. Using the
      fluorescence microscopic spectrometry, cADPR was found to produce a large rapid
      Ca(2+) release from beta-escin-permeabilized renal arterial smooth muscle cells
      (SMCs). In isolated, perfused, and pressurized small renal arteries, cADPR
      produced a concentration-dependent vasoconstriction when added into the bath
      solution. The vasoconstrictor effect of cADPR was completely blocked by
      tetracaine, a Ca(2+)-induced Ca(2+) release (CICR) inhibitor. These results
      suggest that an enzymatic pathway for cADPR production and metabolism is present
      along the renal vasculature and that cADPR may importantly contribute to the
      control of renal vascular tone through CICR.

PMID- 10964590
TI  - Longitudinal differences in vascular control mechanisms in isolated resistance
      arteries of the rat cremaster muscle.
AB  - The purpose of this study was to determine if there are intrinsic differences in
      resting tone, vascular reactivity, myogenic responses, and neurogenic
      vasoconstriction between the large and small feeder arteries and first order
      arterioles (1A) of the rat cremaster muscle. The pudic-epigastric artery (PEA),
      external spermatic artery (ESA), and 1A were isolated and changes in vessel
      diameter were recorded in response to: (1) increases in intralumenal pressure,
      (2) inhibition of nitric oxide synthase (NOS), (3) norepinephrine (NE), (4)
      acetylcholine (ACh), and (5) perivascular nerve stimulation. Vessel responses to
      Ca(2+)-free physiological salt solution were measured to assess resting tone,
      which was significantly greater in the ESA and 1A compared to the PEA. NE caused
      a significant constriction of all vessels, with 1A exhibiting the greatest
      sensitivity. NOS inhibition did not alter vascular sensitivity to NE, but
      enhanced resting tone in ESA and 1A. ACh induced significant dilation in ESA and
      1A, with minimal effect on PEA. The myogenic response was not different between
      ESA and 1A, but was minimal in PEA. Perivascular nerve stimulation induced a
      significant vasoconstriction in all vessels tested. These results suggest that
      the relative importance of different vascular control mechanisms varies
      substantially at different levels of the cremasteric arterial network and that
      the ESA and 1A may be the major site of active vascular regulation upstream from
      the cremaster muscle microcirculation.

PMID- 10964591
TI  - Oxygen diffusion coefficient in isolated chicken red and white skeletal muscle
      fibers in ontogenesis.
AB  - Oxygen diffusion from medium to cultured isolated muscle fibers from red
      gastrocnemius muscle (deep part) (RGM) and white pectoralis muscle (WPM) of
      embryonic and postnatal chickens (about 6 months) was explored. The intracellular
      effective O(2) diffusion coefficient (D(i)) in muscle fiber was calculated from a
      model of a cylindrical fiber with a uniform distribution of an oxygen sink based
      on these experimentally measured parameters: critical tension of O(2) (PO(2)) on
      the surface of a fiber, specific rate of O(2) consumption by a weight unit of
      muscle fibers (;VO(2)), and average diameter of muscle fibers. The results
      document the rapid hypertrophic growth of RGM fibers when compared to WPM fibers
      in the second half of the embryonic period and the higher values of;VO(2) and
      critical PO(2) during the ontogenetic period under study. The oxygen D(i) in RGM
      fibers of embryos and 1-day chickens was two to three times higher than observed
      for WPM fibers. For senior chickens, the oxygen D(i) value in RGM and WPM fibers
      does not differ. The D(i) of O(2) in both RGM and WPM fibers increased from 1.4
      2.7 x 10(-8) to 90-95 x 10(-8) cm(2)/s with an ontogenetic increase in fiber
      diameter from 7. 5 to 67.0 microm. At all stages the oxygen D(i) values in RGM
      and WPM fibers are significantly lower than the O(2) diffusion coefficient in
      water: for 11-day embryos they are 889 and 1714 times lower and for adult
      individuals 25 and 27 times lower, respectively. Why oxygen D(i) values in RGM
      and WPM fibers are so low and why they are gradually increasing during the course
      of hypertrophic ontogenetic growth are still unclear.

PMID- 10964592
TI  - Angiogenesis stimulated by mechanical loading.

PMID- 10964593
TI  - Shear stress-induced cytoskeleton rearrangement mediates NF-kappaB-dependent
      endothelial expression of ICAM-1.

PMID- 10964594
TI  - Interpretation of quantitative measurement of skin capillaries using native in
      vivo microscopy.

PMID- 10964595
TI  - Poly(ADP-ribose) polymerase-1 in the nervous system.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme, activated by DNA
      strand breaks to participate in DNA repair. Overactivation of PARP by cellular
      insults depletes its substrate NAD(+) and then ATP, leading to a major energy
      deficit and cell death. This mechanism appears to be prominent in vascular stroke
      and other neurodegenerative processes in which PARP gene deletion and PARP
      inhibiting drugs provide major protection. Cell death associated with PARP-1
      overactivation appears to be predominantly necrotic while apoptosis is associated
      with PARP-1 cleavage, which may conserve energy needed for the apoptotic process.
      Novel forms of PARP derived from distinct genes and lacking classic DNA-binding
      domains may have nonnuclear functions, perhaps linked to cellular energy
      dynamics.

PMID- 10964597
TI  - NT-4/5 exacerbates free radical-induced neuronal necrosis in vitro and in vivo.
AB  - Neurotrophins render neurons highly vulnerable to certain injuries. We examined
      the possibility that NT-4/5 would enhance free radical neurotoxicity in vivo as
      well as in vitro. Striatal neurons exposed to 10 microM Fe(2+) or 1 mM l
      buthionine-[S, R]-sulfoximine (BSO) underwent mild degeneration within 24 h. With
      concurrent addition of 10-100 ng/ml NT-4/5, neuronal death following exposure to
      Fe(2+) or BSO was significantly increased and suppressed by addition of 100
      microM trolox, an antioxidant. In the adult brain, the intrastriatal injections
      of 20 nmol Fe(2+) revealed features of neuronal necrosis such as swelling cell
      body and mitochondria, fenestration of plasma membrane prior to nuclear membrane,
      and scattering condensation of nuclear chromatin. Cotreatment with 1.8 microg NT
      4/5 augmented the striatal damage 24 h following the injections of Fe(2+). This
      study implies that free radicals produce necrotic degeneration in vivo as well as
      in vitro that becomes more sensitive in the presence of neurotrophins.

PMID- 10964596
TI  - Oxidative stress and genetics in the pathogenesis of Parkinson's disease.
AB  - Parkinson's Disease (PD) is the second most common chronic neurodegenerative
      disease characterized by the progressive loss of dopamine neurons, leading to
      rigidity, slowness of movement, rest tremor, gait disturbances, and imbalance.
      Although there is effective symptomatic treatment for PD, there is no proven
      preventative or regenerative therapy. The etiology of this disorder remains
      unknown. Recent genetic studies have identified mutations in alpha-synuclein as a
      rare cause of autosomal dominant familial PD and mutations in parkin as a cause
      of autosomal recessive familial PD. The more common sporadic form of PD is
      thought to be due to oxidative stress and derangements in mitochondrial complex I
      activity. Understanding the mechanism by which familial linked mutations and
      oxidative stress cause PD has tremendous potential for unraveling the mechanisms
      of dopamine cell death in PD. In this article, we review recent advances in the
      understanding of the role of genetics and oxidative stress in the pathogenesis of
      PD.

PMID- 10964598
TI  - Source localization and possible causes of interictal epileptic activity in tumor
      associated epilepsy.
AB  - Electrophysiological studies in gliomas have demonstrated action potentials in
      neoplastic cells. These "spiking tumor cells" are, however, an enigma. In attempt
      to find evidences for spikes within tumoral borders, 21 patients with different
      intracerebral tumors were preoperatively screened for the occurrence of
      epileptogenic discharges using multichannel MEG and EEG. A correlation between
      histopathology and the distance between dipole and tumor border could be found.
      Glioma patients showed epileptic activities closer to the border than those with
      mixed glioneuronal neoplasms and metastases. Four glioma patients demonstrated
      epileptic activity within the tumor boundary, however, not in the deep center of
      the tumor. Patch-clamping of cells from acute glioma slices did not yield a
      correlation between the presence of voltage-gated sodium channels in tumor cells
      and the MEG/EEG data. Our results demonstrate that the zone with the highest
      epileptogenic potential is different in gliomas and other brain tumors. However,
      our data do not strongly suggest that glioma cells are directly involved in the
      generation of tumor-associated epilepsy in vivo via their capability to generate
      action potentials.

PMID- 10964599
TI  - Evidence for oxidative stress in experimental prion disease.
AB  - Oxidative stress has been shown to be important in several neurodegenerative
      disorders. Previous in vitro studies have already demonstrated the ability of a
      prion protein fragment to induce oxidative stress in cultured cells. By
      immunohistochemistry for nitrotyrosine (NT) and heme oxygenase-1 as markers for
      oxidative stress, we found widespread neuronal labeling for NT in scrapie
      infected mouse brains, in agreement with peroxynitrite mediated neuronal
      degeneration. Damage by free radicals is a likely cause for neurodegeneration in
      prion disease, and antioxidants are a potential therapy of these disorders.

PMID- 10964600
TI  - Differential screening of mutated SOD1 transgenic mice reveals early up
      regulation of a fast axonal transport component in spinal cord motor neurons.
AB  - In the present study we analyze the molecular mechanisms underlying motor neuron
      degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used
      a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene
      with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of
      human FALS. Using an optimized suppression subtractive hybridization method, a
      cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal
      cord of G86R mice was identified by sequence analysis as the KIF3-associated
      protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed
      that KAP3 induction was an early event arising long before axonal degeneration.
      Immunohistochemical studies further revealed that KAP3 protein predominantly
      accumulates in large motor neurons of the ventral spinal cord. We further
      demonstrated that KAP3 up-regulation occurs independent of any change in the
      other components of the kinesin II complex. However, since the ubiquitous KIF1A
      motor is up-regulated, our results show an early and complex rearrangement of the
      fast axonal transport machinery in the course of FALS pathology.

PMID- 10964601
TI  - Optical imaging reveals characteristic seizure onsets, spread patterns, and
      propagation velocities in hippocampal-entorhinal cortex slices of juvenile rats.
AB  - We have combined recordings with extracellular microelectrodes or ion-sensitive
      electrodes and imaging of intrinsic optical signal changes to study the
      spatiotemporal pattern of seizure onset and spread during development. We have
      employed the entorhinal cortex-hippocampus brain slice preparation of juvenile
      rats at different stages of postnatal maturation. Three age groups were analyzed:
      4-6 days (age group I), 10-14 days (age group II), and 20-23 days (age group
      III). Seizure-like events were induced by perfusion of slices with Mg(2+)-free
      artificial cerebrospinal fluid thereby removing the Mg(2+) block of the N-methyl
      d-aspartate receptor. Seizure susceptibility was highest in age groups II and
      III. In age group I seizure-like events originated mainly in the hippocampus
      proper. Seizure-like events in age group II originated mainly in the entorhinal
      cortex and this tendency was even more pronounced in age group III. Invasion of
      the hippocampal formation via the perforant path-dentate gyrus and via the
      subiculum was seen in age groups I and II. In contrast, in age group III the
      hippocampus was invaded exclusively via the subiculum pathway. The velocity of
      spread at which seizure-like events propagated within different regions of the
      slice increased with postnatal age. The characteristics of onset, spread
      patterns, and propagation velocities as revealed by this study allow insight into
      the evolving properties of the developing brain.

PMID- 10964602
TI  - Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel
      activity in rat cerebellar granule cells treated with the prion protein fragment
      106-126.
AB  - Prion diseases are neurodegenerative pathologies characterized by the
      accumulation, in the brain, of altered forms of the prion protein (PrP), named
      PrP(Sc). A synthetic peptide homologous to residues 106-126 of PrP (PrP106-126)
      was reported to maintain the neurodegenerative characteristics of PrP(Sc). We
      investigated the intracellular mechanisms involved in PrP106-126-dependent
      degeneration of primary cultures of cerebellar granule neurons. Prolonged
      exposure of such neurons to PrP106-126 induced apoptotic cell death. The L-type
      voltage-sensitive calcium channel blocker nicardipine reproduced this effect,
      suggesting that blockade of Ca(2+) entry through this class of calcium channels
      may be responsible for the granule cell degeneration. Microfluorometric analysis
      showed that PrP106-126 caused a reduction in cytosolic calcium levels, elicited
      by depolarizing K(+) concentrations in these neurons. Electrophysiological
      studies demonstrated that PrP106-126 and nicardipine selectively reduce the L
      type calcium channel current. These data demonstrate that PrP106-126 alters the
      activity of L-type voltage-sensitive calcium channels in rat cerebellar granule
      cells and suggest that this phenomenon is related to the cell death induced by
      the peptide.

PMID- 10964604
TI  - Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a
      transgenic mouse model.
AB  - Recent data suggest that cholesterol metabolism is linked to susceptibility to
      Alzheimer's disease (AD). However, no direct evidence has been reported linking
      cholesterol metabolism and the pathogenesis of AD. To test the hypothesis that
      amyloid beta-peptide (Abeta) deposition can be modulated by diet-induced
      hypercholesterolemia, we used a transgenic-mouse model for AD amyloidosis and
      examined the effects of a high-fat/high-cholesterol diet on central nervous
      system (CNS) Abeta accumulation. Our data showed that diet-induced
      hypercholesterolemia resulted in significantly increased levels of formic acid
      extractable Abeta peptides in the CNS. Furthermore, the levels of total Abeta
      were strongly correlated with the levels of both plasma and CNS total
      cholesterol. Biochemical analysis revealed that, compared with control, the
      hypercholesterolemic mice had significantly decreased levels of sAPPalpha and
      increased levels of C-terminal fragments (beta-CTFs), suggesting alterations in
      amyloid precursor protein processing in response to hypercholesterolemia.
      Neuropathological analysis indicated that the hypercholesterolemic diet
      significantly increased beta-amyloid load by increasing both deposit number and
      size. These data demonstrate that high dietary cholesterol increases Abeta
      accumulation and accelerates the AD-related pathology observed in this animal
      model. Thus, we propose that diet can be used to modulate the risk of developing
      AD.

PMID- 10964603
TI  - Astrocytes are more resistant than neurons to the cytotoxic effects of increased
      [Zn(2+)](i).
AB  - Increased intracellular free Zn(2+) ([Zn(2+)](i)) is toxic to neurons. Glia are
      more resistant to Zn(2+)-mediated toxicity; however, it is not known if this is
      because glia are less permeable to Zn(2+) or if glia possess intrinsic mechanisms
      that serve to buffer or extrude excess [Zn(2+)](i). We used the Zn(2+)-selective
      ionophore pyrithione to directly increase [Zn(2+)](i) in both neurons and
      astrocytes. In neurons, a 5-min exposure to 1 microM extracellular Zn(2+) in
      combination with pyrithione produced widespread toxicity, whereas extensive
      astrocyte injury was not observed until extracellular Zn(2+) was increased to 10
      microM. Measurements with magfura-2 demonstrated that pyrithione increased
      [Zn(2+)](i) to similar levels in both cell types. We also measured how increased
      [Zn(2+)](i) affects mitochondrial membrane potential (Deltapsi(m)). In
      astrocytes, but not in neurons, toxic [Zn(2+)](i) resulted in an acute loss of
      Deltapsi(m), suggesting that mitochondrial dysregulation may be an early event in
      [Zn(2+)](i)-induced astrocyte but not neuronal death.

PMID- 10964605
TI  - Expression of caspases and their substrates in the rat model of focal cerebral
      ischemia.
AB  - Experimental evidence suggests that the massive release of glutamate during
      experimental brain ischemia both directly and indirectly regulates downstream
      mechanisms of cell suicide. Cerebral ischemia was produced by distal, permanent
      occlusion of the middle cerebral artery (MCAO) in the rat. Sets of three animals
      and one sham-operated for each time-point were kept alive for 0-30 min, 1, 4, 12,
      24, and 48 h, and 4 days. Additional animals were treated by local administration
      of a 10 microM (in 10 microl) cocktail of caspase inhibitors (YVAD-cmk, DEVD-fmk,
      IETD). Immunohistochemistry was performed on free-floating tissue sections with
      goat polyclonal antibodies to procaspase-1, -2, -3, -6, and -8. Some sections
      were processed for double-labeling procaspase immunohistochemistry and in situ
      end-labeling of nuclear DNA fragmentation (TUNEL method). Both
      immunohistochemistry and double-labeling procaspase immunohistochemistry and
      TUNEL method were carried out on formalin-fixed sections. For gel electrophoresis
      and Western blotting, we used antibodies to poly (ADP-ribose) polymerase (PARP),
      lamin B, and PKC-delta, as specific cleavage substrates of caspases. There was
      increased immunoreactivity ipsilaterally in the areas corresponding to the
      infarct and surrounding penumbra with the peak of immunoreactivity between 12 and
      24 h for most of the procaspases. Procaspases were present early in the infarcted
      tissue neurones and their dendrites and axons. Additional procaspase expression
      occurred in astrocytes and microglial cells at different times following
      ischemia. Cells with positive in situ end-labeling of nuclear DNA fragmentation
      appeared in high number predominantly in the infarcted areas and at the edge of
      the infarction and colocalized with enhanced procaspase expression. These
      findings suggest increased procaspase expression in dying cells at the edge of
      the infarction. A major product of PARP degradation of about 89 kDa was found in
      the samples taken from the infarcted and penumbra areas. There was no difference
      in the intensity of the bands corresponding to lamin B or PKC-delta. Injection of
      procaspase inhibitors reduced the levels of major PARP products of 89 kDa and
      decreased the number of TUNEL-positive cells at 12 h post-MCAO. In conclusion,
      these results give support to further research on the use of caspase inhibitors
      as add-on therapeutic agents for the treatment of ischemia.

PMID- 10964606
TI  - MPP(+) injection into rat substantia nigra causes secondary glial activation but
      not cell death in the ipsilateral striatum.
AB  - Injection of MPP(+) into the substantia nigra causes extensive necrosis and
      anterograde degeneration of pars compacta dopaminergic neurons. We studied
      secondary effects in the ipsilateral striatum by examining dopaminergic
      terminals, signs of neuronal damage, and glial reactivity at 1, 2, 3, and 7 days
      after injection of MPP(+) into the substantia nigra. Dopaminergic terminals and
      uptake sites were evaluated with [(3)H]GBR-12935 binding and tyrosine hydroxylase
      immunoreactivity. Glial reaction was examined with markers of astrocytes and
      microglia. Stereology was used to evaluate any changes in neuronal density.
      Tyrosine hydroxylase immunoreactivity and [(3)H]GBR-12935 binding markedly
      decreased (74%) from days 2 to 7. Loss of dopaminergic terminals in the
      ipsilateral striatum was accompanied by an intense astroglial and, to a lesser
      extent, microglial reaction. However, no signs of cell damage, neuronal loss, or
      disruption of the blood-brain barrier were found in the striatum. Resident
      astroglial and microglial cells showed a morphological shift and notable changes
      in protein expression typical of glial reactivity, yet the presence of macrophage
      like cells was not detected. This study shows that injection of MPP(+) in the
      substantia nigra causes a secondary reaction within the ipsilateral striatum
      involving the transformation of quiescent glia to reactive glia. It is suggested
      that stimuli derived from damaged dopaminergic terminals within the striatum are
      able to activate resident glia and that this glial transformation may promote
      repair and regeneration.

PMID- 10964608
TI  - A novel neuroprotective mechanism of riluzole: direct inhibition of protein
      kinase C.
AB  - In addition to its antiexcitotoxic action, the anti-amyotrophic lateral sclerosis
      (ALS) neuroprotectant riluzole protects against nonexcitotoxic oxidative neuronal
      injury. In light of evidence that protein kinase C (PKC) mediates oxidative
      stress in cortical culture, we examined the possibility that riluzole's
      antioxidative neuroprotection involves PKC inhibition. Riluzole (30 microM)
      blocked phorbol 12-myristate 13-acetate (PMA)-induced increases in membrane PKC
      activity in cultured cortical cells. Suggesting a direct action, riluzole also
      inhibited the activity of purified PKC. Consistently, both PKC depletion and
      oxidative neuronal death induced by PMA were markedly attenuated by riluzole. The
      site of action of riluzole on PKC was not likely the diacylglycerol binding site
      but the catalytic domain, since riluzole did not alter radiolabeled phorbol-12,13
      dibutyrate binding, but inhibited PKM, the catalytic domain of PKC. However,
      increasing ATP concentrations did not alter the inhibition of PKC by riluzole,
      making it unlikely that riluzole is a competitive inhibitor of ATP binding at
      PKM. Present results have demonstrated that riluzole directly inhibits PKC, which
      action may contribute to its antioxidative neuroprotective effects. In addition,
      it appears possible that PKC inhibition may be able to explain some of its well
      known channel inhibitory and neuroprotective effects. Combined with findings that
      PKC activity is increased in ALS, the present results suggest that PKC may be a
      potential therapeutic target in ALS.

PMID- 10964607
TI  - Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous
      nonsynaptic bursting in vitro.
AB  - We hypothesized that overexpression of specific glutamate receptors within the
      hippocampus would induce seizures and the associated cellular changes seen in
      temporal lobe epilepsy (TLE). The GluR6 kainate receptor was overexpressed by
      injecting rat hippocampi with HSVGluR6, a viral vector transducing fully edited
      GluR6. These animals experienced limbic seizures approximately 4 h following the
      injection. Control animals injected with HSVlac, a vector expressing beta
      galactosidase, did not have seizures. Recordings from hippocampal CA1 pyramidal
      cells were performed 12 to 48 h and 1 week to 1 month postinjection. We observed
      nonsynaptic Na(+)-mediated bursting in 77.5% of cells 12 to 48 h following
      injection of HSVGluR6 but not HSVlac. The synaptic responses were normal in both
      groups. However, the physiological properties of cells from HSVGluR6-injected
      hippocampi changed over time. Two weeks following HSVGluR6 injection, synaptic
      bursts could be evoked, but intrinsic bursting became rare. These changes
      persisted for at least 1 month. We postulate that this transition from intrinsic
      to synaptic hyperexcitability may be important in the development of TLE.

PMID- 10964609
TI  - HIV- and FIV-derived gp120 alter spatial memory, LTP, and sleep in rats.
AB  - Human immunodeficiency virus (HIV)-associated dementia (HAD) has been detected in
      20-30% of patients suffering AIDS. The envelope glycoprotein 120 (gp120) derived
      from HIV seems to play a critical role in the pathophysiology of this dementia.
      Likewise, the feline immunodeficiency virus (FIV)-derived gp120 causes
      neurological and electrophysiological abnormalitites in cats. We have studied the
      effects of gp120 derived from HIV or FIV on learning and memory processing,
      hippocampal long-term potentiation (LTP), hippocampal neuronal cAMP production,
      the sleep-waking cycle, and locomotor activity and equilibrium in rats. Results
      showed that while both HIV- and FIV-gp120 impaired the rat's performance in the
      Barnes maze task, only HIVgp120 impaired the induction and maintenance of LTP.
      However, both glycoproteins induced a significant decrease in the posttetanic
      potentiation. HIVgp120 also caused a significant reduction in cAMP production in
      the hippocampus. Regarding the sleep-waking cycle, HIV- and FIV-gp120 increased
      the waking state and slow-wave sleep 1 (SWS1), while decreasing both SWS2 and REM
      sleep. Locomotor activity and equilibrium were significantly altered by these
      glycoproteins. These results suggest that HIVgp120 causes neurophysiological
      abnormalities and therefore may facilitate HAD development in AIDS patients.

PMID- 10964610
TI  - beta-amyloid peptides are cytotoxic to astrocytes in culture: a role for
      oxidative stress.
AB  - beta-Amyloid is cytotoxic to neurons in culture by increasing hydrogen peroxide
      and altering calcium homeostasis. We have evaluated the cytotoxicty of beta
      amyloid peptides (betaA(25-35) and betaA(1-40)) and generation of hydrogen
      peroxide on cortical cultured astrocytes. Twenty-four hours after a single
      addition of either betaA(25-35) or betaA(1-40) there was a concentration
      dependent decrease in viability. This toxicity never exceeded 50% of the
      population independently of exposure time and concentrations. The subpopulation
      of astrocytes resistant to betaA(25-35) effects were also insensitive to
      peroxide. Catalase or vitamin E showed no protective effect against betaA(25-35)
      toxicity. Dithiothreitol (DTT), N-acetylcysteine (NAC), and cyclosporine A
      significantly prevented the toxic effects of both betaA(25-35) and peroxide.
      Inhibition of peroxide detoxifying enzymes increased betaA(25-35) and peroxide
      toxicity. Exposure to betaA(25-35) or betaA(1-40) increased peroxide production
      at 2 and 24 h, which was prevented by DTT and NAC, but not vitamin E. Despite the
      inability of added catalase to reduce betaA toxicity, these results suggest that
      betaA-induced cytotoxicity to astrocytes in culture is, as in neurons, mediated
      by generation of hydrogen peroxide.

PMID- 10964611
TI  - Alteration of the Bcl-x/Bax ratio in a transgenic mouse model of amyotrophic
      lateral sclerosis: evidence for the implication of the p53 signaling pathway.
AB  - Molecular mechanisms promoting neuronal death in amyotrophic lateral sclerosis
      (ALS) were investigated using transgenic mice that overexpressed the G86R mutated
      form of the Cu/Zn superoxide dismutase (SOD1) gene. We observed: (i) alteration
      of the Bcl-x/Bax ratio and (ii) activation of the transcription factor p53, as
      deduced from its location within neuron nuclei. We further demonstrated that
      ectopic expression of the G86R mutant SOD1 in PC12 cells enhanced both p53
      expression and phosphorylation, leading to transcriptional stimulation of p53
      responsive genes. These findings provide evidence that the p53 signaling pathway
      is activated in SOD1-linked familial ALS and may play a causative role in spinal
      cord neuron apoptosis by modulating the Bcl-x/Bax ratio.

PMID- 10964612
TI  - Translational control of ribosomal protein L4 mRNA is required for rapid neurite
      regeneration.
AB  - Under some circumstances neurons can be primed to rapidly regenerate injured
      neuritic processes independent of new gene expression. Such transcription
      independent neurite extension occurs in adult rat sensory neurons cultured after
      sciatic nerve crush and in NGF-differentiated PC12 cells whose neurites have been
      mechanically sheared. In the PC12 cells, neurite regeneration occurs by means of
      translational control of mRNAs which were transcribed prior to neurite injury.
      The survival of such translationally regulated mRNAs is relatively short in the
      differentiated PC12 cells (< or =10 h). By subtractive hybridization, we have
      isolated a short-lived mRNA from differentiated PC12 cells. This mRNA, which
      encodes the ribosomal protein L4, is translationally regulated during neurite
      regeneration in PC12 cells. Antisense oligonucleotides to L4 mRNA inhibit neurite
      regeneration from the differentiated PC12 cells as well as axonal elongation from
      conditioned sensory neurons, indicating that ongoing translation of L4 mRNA is
      needed for these forms of rapid transcription-independent neurite growth. Taken
      together, these data point to the importance of translational regulation of
      existing neuronal mRNAs in the regenerative responses to neuronal injury.
      Although there are other examples of neuronal translational control, there are no
      other known neuronal proteins whose levels are regulated predominantly by
      translational rather than transcriptional control.

PMID- 10964613
TI  - The single intranigral injection of LPS as a new model for studying the selective
      effects of inflammatory reactions on dopaminergic system.
AB  - We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats
      in order to address the role of inflammation in Parkinson's disease (PD). LPS
      induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a
      characteristic clustering of macrophage cells around blood-vessels. The SN was
      far more sensitive than the striatum to the inflammatory stimulus. Moreover, only
      the dopaminergic neurons of the SN were affected, with no detectable damage to
      either the GABAergic or the serotoninergic neurons. The damage to the DA neurons
      in the SN was permanent, as observed 1 year postinjection. Unlike the direct
      death of dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS seems to
      cause indirect death due to inflammatory reaction. Therefore, we suggest that the
      injection of a single dose of LPS within the SN is an interesting model for
      studying the selective effects of inflammatory reaction on dopaminergic system
      and also potentially useful for studying PD.

PMID- 10964614
TI  - Ceramide initiates NFkappaB-mediated caspase activation in neuronal apoptosis.
AB  - The objective of the present study was to evaluate the role of ceramide in
      mediating apoptosis of dorsal root ganglion neurons induced by either nerve
      growth factor withdrawal or treatment with the chemotherapeutic agents suramin
      and cisplatin. Measurement of ceramide accumulation by mass spectrometry and the
      diacylglycerol kinase assay revealed elevation of intracellular ceramide only in
      suramin treated cultures. Ceramide-mediated neuronal cell death was inhibited by
      the caspase inhibitor zVAD.fmk. In these experimental models, ceramide
      accumulation mediated activation and nuclear translocation of the transcription
      factor NFkappaB and cyclin D1 protein expression. Specific inhibition of NFkappaB
      using a molecular decoy strategy resulted in increased cell viability accompanied
      by diminished caspase activity and cyclin D1 expression. Inhibition of NFkappaB
      did not alter intracellular ceramide levels. Our study suggests that ceramide
      generation occurs upstream of NFkappaB activation, cell cycle reentry, and
      caspase activation in the neuronal death pathway.

PMID- 10964615
TI  - Extra axonal neurofilaments do not exacerbate disease caused by mutant Cu,Zn
      superoxide dismutase.
AB  - A recent report by T. L. Williamson et al. (1998, Proc. Natl. Acad. Sci. USA 95,
      9631-9636) showed that disease caused by expression of mutant Cu,Zn superoxide
      dismutase (SOD1) in mice was slowed down by disruption of the neurofilament light
      (NF-L) gene. This led to the conclusion that decreasing the axonal amount of
      neurofilaments reduces the vulnerability of motor neurons to toxicity mediated by
      mutant SOD1. We report here that, unexpectedly, overexpression of human NF-L
      proteins resulting in extra axonal neurofilaments does not shorten the life span
      of transgenic mice expressing a mutant SOD1 (SOD1(G37R)). Microscopic examination
      of spinal cord and ventral roots even shows modest protective effects of NF-L
      overexpression. These results suggest that axonal neurofilaments are not an
      exacerbating factor in motor neuron disease mediated by mutant SOD1 and that
      perikaryal neurofilaments may even have beneficial effects.

PMID- 10964616
TI  - Differential involvement of L-type calcium channels in epileptogenesis of rat
      hippocampal slices during ontogenesis.
AB  - Organic calcium channel antagonists block epileptiform activity in adult tissue,
      suggesting an essential role of L-type channels in epileptogenesis in the mature
      CNS. By contrast, this remains doubtful for neonatal tissue, as the density of
      calcium channels changes markedly with ontogenesis. The paper addresses this
      question by exploring the antiepileptic efficacy of the L-type calcium channel
      blockers verapamil and nifedipine in low-Mg(2+)-epilepsy in rat hippocampal
      slices of different postnatal (PN) ages. Field (CA3, CA1) and membrane potentials
      (CA3) were recorded. Washout of Mg(2+) induced epileptiform potentials, which
      were blocked age-dependently: Verapamil suppressed activity in all preparations
      of PN1-5 and PN13-30+, but only in 70% of PN6-12. Nifedipine depressed activity
      in >75% of slices of PN13-30+, but only in 33% of PN1-12. The findings indicate a
      role of L-type calcium channels in epileptogenesis from PN13 onwards, with
      phenylalkylamine-sensitive calcium channels also being involved during PN1-5.

PMID- 10964617
TI  - Enhanced proliferation and potassium conductance of Schwann cells isolated from
      NF2 schwannomas can be reduced by quinidine.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that is
      characterized mainly by schwannomas, as well as menigiomas and gliomas. The NF2
      gene product merlin/schwannomin acts as a tumor suppressor. Schwann cells derived
      from NF2 schwannomas showed an enhanced proliferation rate, and
      electrophysological studies revealed larger K(+) outward currents as compared
      with controls. Schwann cells isolated from schwannomas of NF2 patients or
      multiorgan donors were treated with different concentrations of the K(+) current
      blockers quinidine, tetraethylammonium chloride, and 4-aminopyridine and K(+)
      outward currents and proliferation rates of these cells were compared. K(+)
      outward currents of both cell types can be blocked by quinidine. Importantly,
      treatment with quinidine reduces proliferation of NF2 Schwann cells in a
      concentration dependent manner but did not reduce proliferation of normal Schwann
      cells. Therefore, the use of quinidine or quinidine-like components would
      possibly provide a novel adjuvant therapeutic option for NF2 patients to slow
      down or freeze growth of schwannomas.

PMID- 10964622
TI  - Replication of oriJ-based plasmid DNA during the stringent and relaxed responses
      of Escherichia coli.
AB  - The oriJ-based plasmids contain the origin of DNA replication from the cryptic
      Rac prophage, present in the chromosomes of most Escherichia coli K-12 strains.
      The organization of the oriJ replication region resembles that of the
      bacteriophage lambda, although sequence similarity is small. Here we investigated
      the regulation of replication of the oriJ-based plasmid in E. coli relA(+) and
      relA(-) hosts during amino acid starvation and limitation, i.e., during the
      stringent and relaxed responses. We found that, contrary to plasmids derived from
      phage lambda, replication of the oriJ-based plasmid proceeds efficiently during
      both stringent and relaxed responses. On the other hand, density shift
      experiments and measurement of the stability of a putative replication initiator
      protein (the lambda O protein homologue) suggest that this replication may be
      carried out by the heritable replication complex, as previously demonstrated for
      lambda plasmids. We demonstrate that contrary to bacteriophage lambda p(R)
      promoter, an analogous promoter from the oriJ region is activated rather than
      inhibited at increased ppGpp levels. We propose that various responses of these
      promoters (p(R) and p(R-Rac), which are necessary for transcriptional activation
      of orilambda and perhaps oriJ, respectively) to ppGpp are responsible for
      differences in the replication regulation between orilambda- and oriJ-based
      plasmids during the stringent response.

PMID- 10964623
TI  - Characterization and replication properties of the Zymomonas mobilis ATCC 10988
      plasmids pZMO1 and pZMO2.
AB  - The complete nucleotide sequences of two small cryptic Zymomonas mobilis ATCC
      10988 plasmids (pZMO1 and pZMO2) were determined. The plasmids showed 67%
      homology to each other at their nucleotide level. Plasmid pZMO1 was 1651 bp long
      with 38% G + C content and contained an open reading frame (ORFZMO1) of 1044
      nucleotides. ORFZMO1 is predicted to encode a polypeptide of 348 amino acids and
      shows a high degree of homology with gram-negative replication proteins of
      rolling circle replicating plasmids, which belong to the pC194/pUB110 family.
      Plasmid pZMO2 was found to be 1669 bp long, with a 38.5% G + C content, and it
      contained an ORF of 552 nucleotides (ORFZMO2) encoding a putative polypeptide of
      184 amino acids. This polypeptide also shows a high degree of homology with the
      replication proteins of RCR plasmids of gram-negative bacteria, but only at their
      N-termini. The region necessary for replication of both plasmids was determined
      by stability tests under nonselective conditions, following cloning in pBR325 and
      introduction in Z. mobilis ATCC 10988 by pRK2013 assisted conjugation. Double-
      and single-strand origin regions were predicted by sequence analysis. Detection
      of single-stranded DNA in the extract of exponentially growing cells confirmed
      experimentally the rolling circle replication mode of at least pZMO2.

PMID- 10964624
TI  - Construction and characterization of a highly regulable expression vector,
      pLAC11, and its multipurpose derivatives, pLAC22 and pLAC33.
AB  - A number of different expression vectors have been developed to facilitate the
      regulated overproduction of proteins in Escherichia coli and related bacteria.
      Some of the more popular ones include pKK223-3, pKK233-2, pTrc99A, and the pET
      family of expression vectors. These vectors were designed to be regulable and can
      be grown under conditions that repress protein production or under conditions
      that induce protein production. Unfortunately, however, numerous researchers have
      found that these vectors produce significant amounts of protein even when grown
      under repressed conditions. We describe here a new expression vector, pLAC11,
      which was designed to be more regulable and thus more tightly repressible when
      grown under repressed conditions. The tight regulation of pLAC11 was achieved by
      utilizing the O3 auxiliary operator, CAP binding site, promoter, and O1 operator
      that occur in the wild-type lac control region. The pLAC11 vector can be used to
      conduct physiologically relevant studies in which the cloned gene is expressed at
      levels comparable to that obtainable from the chromosomal copy of the gene in
      question. In experiments in which a bacterial cell contained both a null allele
      in the chromosome and a second copy of the wild-type allele on pLAC11, we
      observed that cells grown under repressed conditions exhibited the null phenotype
      while cells grown under induced conditions exhibited the wild-type phenotype. Two
      multipurpose derivatives of pLAC11, pLAC22, and pLAC33 have also been constructed
      to fulfill different experimental needs.

PMID- 10964625
TI  - Transcription reporters that shuttle cloned DNA between high-copy Escherichia
      coli plasmids and low-copy broad-host-range plasmids.
AB  - We describe and apply lacZ transcription reporter plasmids designed for both
      biochemical analyses requiring high DNA yield and physiological studies requiring
      low gene dosage. Standard DNA ligations are performed at seven unique restriction
      sites 5' to the lacZ gene on high-copy ColE1 plasmids suitable for double- or
      single-strand DNA sequencing. A divergent gusA transcription reporter is included
      and serves as an internal control. Rec(+) Escherichia coli cells readily shuttle
      DNA placed between gusA and lacZ by allelic exchange with pRK290-based plasmids
      that subsequently conjugate and replicate in most gram-negative bacteria. We
      applied this system to study Caulobacter crescentus cell cycle promoters directed
      by the CtrA response-regulator protein. Synthetic oligonucleotides were ligated
      to create altered CtrA binding sites and corresponding promoters with varied
      transcription strength. We also document the phenomenon of long-range promoter
      interference. A strong promoter can repress up to twofold the transcription from
      a divergent promoter located 100 bp away. However, the cell cycle timing of both
      promoters is not changed. Additional applications of our system and theoretical
      aspects of promoter organization are discussed.

PMID- 10964626
TI  - Characterization of the IncW cryptic plasmid pXV2 from Xanthomonas campestris pv.
      vesicatoria.
AB  - The gram-negative plant pathogen Xanthomonas campestris pv. vesicatoria strain
      Xv2 harbors an indigenous, cryptic plasmid pXV2 of 14.6 kb. This plasmid can only
      be maintained in Xanthomonas and is incapable of self-transmission. However,
      incompatibility testing classified it in IncW, a group containing the smallest
      number of naturally occurring, broad-host-range, conjugative plasmids. A pXV2
      derivative containing only a 5.5-kb PstI fragment is stably maintained. Deletion
      of a 3.0-kb region from the PstI fragment causes a loss of plasmid stability.
      Nucleotide sequencing of the 2. 1-kb region essential for autonomous replication
      revealed a repA gene and a downstream noncoding region containing four iterons,
      two 17- and two 19-nt direct repeats, and an AT-rich region lying between the two
      sets of iterons. The sequence of the deduced RepA and the iterons shows homology
      to the RepA (39% identity) and the iterons, respectively, of the IncW plasmid
      pSa. Maxicell expression of the repA gene produced a protein of 35 kDa, a size
      similar to that deduced from the nucleotide sequence. Trans-complementation test
      confirmed that the repA gene and the iterons are indeed the essential elements
      for pXV2 replication.

PMID- 10964627
TI  - Generation of an improved luciferase reporter gene plasmid that employs a novel
      mechanism for high-copy replication.
AB  - We have engineered the reporter gene plasmid pXPG by incorporating a novel high
      copy origin of replication and a modified luciferase gene into a pXP1-derived
      vector that efficiently blocks read-through transcription in eukaryotic cells.
      pXPG contains the Luc+ luciferase gene derived from pGL3 that lacks a peroxisomal
      targeting sequence, thereby allowing accumulation of luciferase protein in the
      cytoplasm rather than subcellular organelles of transfected eukaryotic cells.
      pXPG has distinct advantages over pGL3, because it contains SV40 polyadenylation
      signals that appear to be more efficient at blocking read-through transcription
      than the synthetic polyadenylation signal present in pGL3. pXPG contains a novel
      mutation near the origin of replication that increases plasmid copy number in
      Escherichia coli. This mutation alters the -10 sequence in the RNA II promoter of
      the ColE1 origin of replication from TAATCT to TAATAT. As this sequence is a
      closer match to the consensus -10 element, we suggest that the mutation increases
      copy number by increasing the rate of transcription of the RNA II replication
      primer. This novel mechanism for increasing copy number may have more widespread
      applications than the commonly used pUC high-copy origin of replication mutation.
      Unlike pUC, which reverts to low copy number at 30 degrees C, the pXPG mutation
      supports a higher copy number at both 37 and 30 degrees C.

PMID- 10964628
TI  - Improved vectors for nisin-controlled expression in gram-positive bacteria.
AB  - A set of shuttle vectors, able to replicate in Escherichia coli and in gram
      positive bacteria, containing a nisin-inducible promoter (PnisA) and genes
      encoding NisR and NisK, the two-component signaling mechanism for activating
      transcription from PnisA in the presence of nisin, was constructed. To test these
      vectors, Enterococcus faecalis pCF10 plasmid genes prgX, prgY, and prgZ, which
      respectively encode cytosolic, integral membrane, and cell surface proteins, were
      cloned downstream of PnisA. Increased protein expression, in the presence of
      nisin, was demonstrated by Western blot analysis.

PMID- 10964629
TI  - Transposon mutagenesis of Mycoplasma gallisepticum by conjugation with
      enterococcus faecalis and determination of insertion site by direct genomic
      sequencing.
AB  - Few genetic systems for studying mycoplasmas exist, but transposon Tn916 has been
      shown to transpose into the genomes of some species and can be used as an
      insertional mutagen. In the current study, the ability of Enterococcus faecalis
      to serve as a donor for the conjugative transfer of transposon Tn916 into the
      genome of the avian pathogen Mycoplasma gallisepticum strain PG31 was examined.
      Transconjugants were obtained at a frequency of > or =6 x 10(-8) per recipient
      CFU. To determine the transposon insertion site, an oligonucleotide primer
      corresponding to the 3' end of Tn916 was designed for the purpose of directly
      sequencing genomic DNA without PCR amplification. Using the direct sequencing
      approach, Tn916 was shown to insert into any of numerous sites in the M.
      gallisepticum genome. This is the first report of conjugal transposition of Tn916
      into the M. gallisepticum genome. The ability to determine transposon insertion
      sites in mycoplasmas by genomic sequencing has not been previously described and
      allows rapid sequence analysis of transposon-generated mutants.

PMID- 10964630
TI  - Characterization of a novel plasmid-encoded HsdS subunit, S.LlaW12I, from
      Lactococcus lactis W12.
AB  - A novel type I restriction-modification specificity subunit, S. LlaW12I, has been
      identified on the naturally occurring 8.0-kb plasmid pAW122 in the lactic acid
      bacterium Lactococcus lactis subsp. cremoris W12. Presence of the HsdS protein
      together with a complete type I restriction-modification system conferred
      increased phage restriction to the host, indicating exchange of specificity
      subunits. Sequence analysis showed that the S.LlaW12I subunit is most probably of
      type IC. Presumably, the hsdS gene is organized together with the repB gene on
      one transcriptional unit.

PMID- 10964631
TI  - A broad-host-range plasmid for isolating mobile genetic elements in gram-negative
      bacteria.
AB  - Plasmid pGBG1 was constructed to isolate mobile genetic elements in a wide
      variety of gram-negative bacteria. The mutation target, carried on a broad-host
      range vector, allows positive selection for tetracycline resistance. In tests
      using several gram-negative bacteria we could detect transposition events of
      either insertion sequences or transposons. A new insertion sequence (IS) element
      was identified in Ralstonia eutropha.

PMID- 10964633
TI  - Page for patients

PMID- 10964632
TI  - Prostate cancer screening trends of New York State men at least 50 years of age,
      1994 to 1997.
AB  - BACKGROUND: Despite the lack of consensus on prostate cancer screening
      recommendations, men are being screened at high rates in some states. Our
      objective was to examine the trends in prostate cancer screening awareness and
      practices from 1994 through 1997 and the relationship among screening practices
      and demographic characteristics, perceived risk, and family history of prostate
      cancer. METHODS: Data from the New York State Behavioral Risk Factor Surveillance
      System surveys and questionnaire modules on prostate cancer screening were used
      for this study, which excluded men younger than 50 years of age and men with a
      history of prostate cancer. The questionnaires were administered by random-digit
      dialed monthly telephone surveys of the civilian, noninstitutionalized adult
      population in New York State. RESULTS: A total of 295, 336, 273, and 448 men, the
      vast majority of whom were white, met the study criteria for 1994, 1995, 1996,
      and 1997, respectively. Each year the percentage of men who reported having heard
      of the prostate specific antigen (PSA) test increased (test for trend, P <
      0.001). Among those who had heard of the PSA test, the percentage who reported
      having had a PSA test increased steadily from 1994 to 1997. About 30% of the men
      in each year's study did not have an impression of their risk of getting prostate
      cancer. CONCLUSIONS: Given the increasing rate at which men are reporting being
      screened for prostate cancer and given their reported perceived risk levels,
      perhaps more needs to be done to educate men about screening implications and
      personal risk for prostate cancer.

PMID- 10964635
TI  - Development and validation of an instrument to assess child dietary fat intake.
AB  - BACKGROUND: brief dietary assessment instrument to assess dietary intakes of
      total fat, saturated fatty acids (SFA), and cholesterol in young children was
      developed and validated. METHODS: Young children and their parent or primary
      caretaker were recruited from a general primary care health center and local Head
      Start programs. Dietary records, entered and analyzed using the Minnesota
      Nutrition Data System, were used to calculate children's mean dietary intakes.
      Stepwise linear regression analysis was used to select questionnaire items that
      best predicted total fat, SFA, and dietary cholesterol intakes. RESULTS: This
      yielded a 17-item Child Dietary Fat Questionnaire (CDFQ); 9 questions correlated
      with total fat intake (r = 0.68, P < 0.0001); 15 questions correlated with SFA
      intake (r = 0.75, P < 0.0001); and 4 questions correlated with dietary
      cholesterol intake (r = 0.57, P < 0.0001). The test-retest reliabilities of the
      CDFQ in predicting children's dietary intakes of total fat, SFA, and cholesterol
      were 0.41, 0.66, and 0.64, respectively. The criterion-based validity of the
      CDFQ, evaluated against 4 days of dietary records, yielded correlations of 0.54
      (P < 0.0001) for total fat, 0.36 (P < 0.01) for SFA, and 0.55 (P < 0. 0001) for
      dietary cholesterol intake. CONCLUSIONS: The 17-item CDFQ is a brief, easy-to-use
      dietary assessment instrument that could be used to identify children with high,
      as well as low, dietary intakes of total fat, SFA, and/or cholesterol.

PMID- 10964634
TI  - Patient delay in seeking care for heart attack symptoms: findings from focus
      groups conducted in five U.S. regions.
AB  - BACKGROUND: Patient delay in seeking health care for heart attack symptoms is a
      continuuing problem in the United States. METHODS: Investigators conducted focus
      groups (N = 34; 207 participants) in major U.S. regions (NE, NW, SE, SW, MW) as
      formative evaluation to develop a multi-center randomized community trial (the
      REACT Project). Target groups included adults with previous heart attacks, those
      at higher risk for heart attack, and bystanders to heart attacks. There were also
      subgroups reflecting gender and ethnicity (African-American, Hispanic-American,
      White). FINDINGS: Patients, bystanders, and those at higher risk expected heart
      attack symptoms to present as often portrayed in the movies, that is, as sharp,
      crushing chest pain rather than the more common onset of initially ambiguous but
      gradually increasing discomfort. Patients and those at higher risk also
      unrealistically judge their personal risk as low, understand little about the
      benefits of rapid action, are generally unaware of the benefits of using EMS/9-1
      1 over alternative transport, and appear to need the "permission" of health care
      providers or family to act. Moreover, participants reported rarely discussing
      heart attack symptoms and appropriate responses in advance with health care
      providers, spouses, or family members. Women often described heart attack as a
      "male problem," an important aspect of their underestimation of personal risk.
      African-American participants were more likely to describe negative feelings
      about EMS/9-1-1, particularly whether they would be transported to their hospital
      of choice. CONCLUSIONS: Interventions to reduce patient delay need to address
      expectations about heart attack symptoms, educate about benefits and appropriate
      actions, and provide legitimacy for taking specific health care-seeking actions.
      In addition, strategy development must emphasize the role of health care
      providers in legitimizing the need and importance of taking rapid action in the
      first place.

PMID- 10964636
TI  - Using entertainment television to build a context for prevention news stories.
AB  - OBJECTIVE. A nationally syndicated television news series called "Following ER"
      was developed to educate viewers about the health issues dramatized on "ER,"
      NBC's award-winning medical drama. This study investigated the impact of this
      prime-time link on viewer attention, satisfaction, information recall, and
      perceptions about the uses and gratifications delivered by a news story. METHODS:
      A total of 458 municipal jurors participated in a randomized 2 ("ER" tie-in vs no
      tie-in) x 2 (familiar vs novel story topic) experiment. The four experimental
      news stories required by this design were developed using footage of previously
      aired local newscasts. RESULTS: In the case of the familiar topic story, the "ER"
      tie-in enhanced the attention and satisfaction of viewers. Participants reported
      that the prime-time link added value by elevating the importance and relevance of
      the commonplace topic. However, the "ER" tie-in did not generate any beneficial
      effects when paired with the novel topic story. CONCLUSIONS: Framing news stories
      about familiar health concerns in the context of television drama represents a
      viable strategy for legitimizing them as important and timely topics for public
      consumption and debate.

PMID- 10964637
TI  - Overweight and depressive symptoms among African-American women.
AB  - BACKGROUND: In a national survey, a correlation between overweight and depression
      was explained by dieting and poor health. This study examines overweight and
      depressive symptoms among urban African-American women, taking into account
      demographic factors, health status and practices, and psychosocial constructs.
      METHODS: Respondents are 429 participants in a pilot for a culturally tailored
      intervention promoting healthful eating and exercising. Anthropomorphic and self
      administered questionnaire data were collected at a community health club site.
      RESULTS: Controlling for demographic factors, overweight is associated with
      symptoms of depression, a relationship that is partially explained by health
      status, but not by dietary restraint. Using multiple regression, poor health
      status, alcohol intake, hostility, and low levels of ethnic identity
      (connectedness with the African-American community) are independent predictors of
      depressed mood. In this study, dietary restraint reflects healthful eating and is
      inversely related to depression. The overweight/depression association is
      stronger among women with high levels of education and high levels of ethnic
      identity (statistical interactions). CONCLUSION: Poor health likely contributes
      over time to both overweight and depressed mood. Ethnic identity enhancement
      strategies should be studied for their effectiveness in strengthening identity
      and for their potential in attracting individuals especially likely to benefit
      from lifestyle change programs.

PMID- 10964638
TI  - Validity of residents' self-reported cardiovascular disease prevention
      activities: the Preventive Medicine Attitudes and Activities Questionnaire.
AB  - BACKGROUND: This article describes the development, reliability, and validity of
      three cardiovascular disease (CVD) prevention subscales-CVD prevention behaviors,
      perceived importance, and perceived effectiveness-of the Preventive Medicine
      Attitudes and Activities Questionnaire (PMAAQ). METHODS: The PMAAQ was
      administered three times to University of Minnesota family practice residents
      (178) over 2 years (91% response rate). Stability measures were calculated, and
      validity was demonstrated in four ways: content validity through an expert panel;
      calculation of internal consistency reliabilities; demonstration of divergent
      validity; and external validation via a separate chart review. RESULTS: High
      internal consistency reliabilities among the subscales were seen (Cronbach's
      alpha = 0.77 to 0.92). Divergent validity was verified by low intercorrelations
      among the subscales (r = -0.23 to 0.27). Two-month test-retest scores ranged from
      Cronbach's alpha = 0.47 to 0.64. Significant correlations were seen between the
      chart review scale and both the CVD behaviors subscale and the PMAAQ smoking
      scale (r = 0.25 and 0.36, respectively). CONCLUSIONS: Results indicate that the
      PMAAQ can validly and reliably measure residents' CVD prevention behaviors and
      provide insight into their preventive health care attitudes. Further, the
      independence among the subscales suggests that importance and effectiveness by
      themselves do not affect behavior and that other factors are likely to be
      important in influencing physician behavior change.

PMID- 10964639
TI  - The Australian National Workplace Health Project: design and baseline findings.
AB  - BACKGROUND: This paper describes the study design, recruitment, measurement, and
      initial recruitment outcomes of Australia's largest workplace intervention trial,
      the National Workplace Health Project. METHODS: This was a cluster-randomized
      trial of socio-behavioral and environmental interventions focusing on key
      behaviors of physical activity, healthy food choices, cigarette smoking, and
      alcohol consumption, as well as motivational readiness for change. Twenty
      worksites were randomized separately for each intervention using a two-by-two
      factorial design. All participants underwent a health risk appraisal and
      measurements were made at baseline and at 1 and 2 years. RESULTS: The overall
      response rate for the baseline survey was 73% with 61% attending the health risk
      appraisal. The sample was predominantly male, English-speaking, married, blue
      collar workers. Overall, 12% reported unsafe alcohol consumption, 26% were
      current smokers, 44% were physically inactive, 74% ate at most one piece of fruit
      per day, and 26% ate at most one serving of vegetables per day. Intervention and
      control conditions were similar at baseline for the primary outcomes, except that
      a higher proportion of the sociobehavioral intervention condition was more
      physically active (59%) than the corresponding control condition (53%).
      CONCLUSIONS: This study will permit the rigorous evaluation of the efficacy of
      sociobehavioral and environ mental intervention approaches to workplace health
      promotion. Although participants were randomized by worksite, intervention and
      control conditions were similar at baseline; any differences in the primary out
      come variables will be controlled for in the analysis.

PMID- 10964641
TI  - Smoking survey at a midwestern U.S. medical center.
AB  - BACKGROUND: In an effort to learn more about the smoking behavior of hospital
      employees, a study was conducted at the University of Kansas Medical Center
      (KUMC) regarding tobacco usage and secondhand smoke exposure. METHODS: An
      anonymous voluntary survey was distributed to 4177 full-time employees in Kansas
      City and Wichita during June and July of 1998. Questions included tobacco usage
      and exposure to secondhand smoke. The survey results were assimilated in a data
      base, which was analyzed in a variety of ways to arrive at several conclusive
      findings. RESULTS: Of the 1187 respondents (28. 4%), 35.1% had smoked at least
      100 cigarettes in their life (41% of those had at least a 10 pack-year history),
      and 11.8% currently smoked. The groups with the highest percentage of current
      smokers were females (12%), blacks (17%), Kansas City campus employees (12%), and
      nonfaculty (13%). Sixty-seven percent of respondents were exposed to secondhand
      smoke in the previous week, and 25% were exposed at KUMC. CONCLUSIONS: After
      arriving at the results of this study, recommendations include starting an
      educational campaign against smoking, promoting cessation programs, moving the
      current smoking area to a less populated area on campus, and investigating a
      total campus ban on smoking.

PMID- 10964640
TI  - The importance of health insurance as a determinant of cancer screening: evidence
      from the Women's Health Initiative.
AB  - BACKGROUND: Amid current changes in health care access across the United States,
      the importance of health insurance status and insurance type relative to
      demographic, actual, and perceived health variables as determinants of screening
      for breast, colorectal, and cervical cancer is uncertain. This analysis evaluates
      the hypothesis that health insurance independently predicts cancer screening in
      the Women's Health Initia tive Observational Study cohort. METHODS: Questionnaire
      data from 55,278 women en rolled in the Women's Health Initiative Observational
      Study between September 1994 and February 1997 were analyzed by multiple logistic
      regression to identify predictors of self-reported mammography within 2 years,
      Pap smear within 3 years, and stool guaiac or flexible sigmoidoscopy within 5
      years. RESULTS: Positive determinants of reporting cancer screening were age,
      ethnic origin, household income, educational level, family history of cancer,
      having a usual care provider, time since last provider visit, and insurance
      status and type. Smoking, diabetes, and, among older women, prior cardiovascular
      events were negative determinants of cancer screening. Among women younger than
      65, lacking health insurance or having fee-for-service insurance was strongly
      associated with failure to report cancer screening, independently of having or
      using a usual care provider and of demographics, self-perceived health, and
      health characteristics. Among women 65 and older, those with Medicare alone were
      less likely, whereas those with Medicare + prepaid insurance were more likely, to
      report cancer screening. CONCLUSIONS: In the Women's Health Initiative Obser
      vational Study, a large, diverse group of older women, health insurance type and
      status were among the most important determinants of cancer screening indepen
      dent of demographics, chronic health conditions, and self-perceived health
      characteristics.

PMID- 10964642
TI  - Increasing taxes as a strategy to reduce cigarette use and deaths: results of a
      simulation model.
AB  - OBJECTIVES: The aim of this study was to develop a simulation model to predict
      the effects of taxes on the smoking rate and smoking-attributable deaths.
      METHODS: The model projects the number of smokers and smoking-related deaths from
      a baseline year forward. The effects of taxes of different sizes, indexed and
      unindexed, and temporary vs sustained are modeled. RESULTS: The model predicts
      that sustained tax increases have the potential to substantially reduce the
      number of smokers and the number of premature deaths, with the effects growing
      over time. Indexing taxes to inflation stems erosion of the tax effect.
      CONCLUSIONS: Tax hikes have the ability to substantially affect smoking rates in
      the near term. These effects grow over time and lead to substantial savings in
      lives and health care costs.

PMID- 10964643
TI  - Plasmodium falciparum: expression of gametocyte-specific genes in monolayer
      cultures and malaria-positive blood samples.
AB  - In order to facilitate molecular epidemiological studies on the transmission of
      the malaria parasite Plasmodium falciparum a sensitive assay for gametocyte
      detection based on RT-PCR was developed. The transcription of the sexual stage
      specific genes Pfs16, Pfs48/45, Pfs230, and Pfs25, as well as the sexual stage-
      and sporozoite-specific S 18S rRNA, was detected by RT-PCR. S 18S rRNA was
      present in seven of nine P. falciparum-positive blood samples, despite the lack
      of microscopic detection of gametocytes and a parasitemia below 0.1%. Expression
      of the other four gametocyte-specific genes was detected less frequently in
      malaria-positive blood samples. These findings indicate that RT-PCR of S 18S rRNA
      is a highly sensitive method for gametocyte detection and, furthermore, that
      gametocytes are present in the peripheral blood of most malaria carriers, even if
      the parasitemia is below 0.1%. To determinate the expression pattern of sexual
      stage-specific genes in more detail, RT-PCR was performed at consecutive time
      points of highly synchronized monolayer cell cultures. Transcripts of all
      examined genes except Pfs25 were detected directly after invasion of merozoites
      of the strain NF54 in red blood cells.

PMID- 10964644
TI  - Strongyloides venezuelensis: heparin-binding adhesion substances in
      immunologically damaged adult worms.
AB  - Immunologically damaged Strongyloides venezuelensis adult worms were examined for
      their mucosal invasion ability and secretion of heparin-binding adhesion
      substances. S. venezuelensis was expelled from male Wistar rats 4 to 5 weeks
      after infection. Four-week-old adult worms were smaller and had fewer eggs than 1
      week-old adult worms. One-week-old, 4-week-old, and 5-week-old adult worms
      equally established in the recipient mouse intestine when surgically implanted.
      Adult worms of 4 and 5 weeks of age secreted adhesion substances as much as 1
      week-old adult worms. There was no difference in the heparin-binding activities
      and the lectin-binding profile of adhesion substances among adult worms of
      different ages. The rate of secretion of adhesion substances from the mouth was
      also identical. Heparin-binding activities were detected in crude adult worm
      proteins; however, proteins of 5-week-old adult worms had weaker heparin-binding
      activities than those of 1-week-old adult worms. Western blotting revealed that a
      number of heparin-binding proteins were lost in 5-week-old adult worms. A heparin
      binding protein of 42. 0 kDa, which was consistently expressed in adult worms,
      was a possible component of heparin-binding adhesion substances which are
      secreted from the mouth.

PMID- 10964645
TI  - Trypanosoma cruzi: a putative vacuolar ATP synthase subunit and a CAAX prenyl
      protease-encoding gene, as examples of gene identification in genome projects.
AB  - An international genome program has been initiated to increase the knowledge
      about the Trypanosoma cruzi genome and thereby find effective tools to treat
      Chagas' disease. We here report the molecular characterization of two novel genes
      found in the course of this project. Two of the open reading frames (ORF)
      identified in the sequencing of the third smallest chromosome of the CL Brener
      strain of T. cruzi were selected for further molecular characterization due to
      their similarity to genes with interesting functions in other organisms and their
      potential as targets to combat the parasite. The first ORF (402 bp) showed
      homology to a 14-kDa vacuolar ATP synthase subunit F from a variety of organisms,
      such as yeast, rat, bovine, human, and a number of prokaryotes. The second ORF
      (1188 bp) resembled a CAAX prenyl protease-encoding gene, identified in different
      organisms, including Homo sapiens, Saccharomyces cerevisiae, and Arabidopsis
      thaliana, as well as several prokaryotes. RT-PCR from T. cruzi total epimastigote
      RNA allowed us to isolate the complete transcripts of these genes. Furthermore,
      screening of an available normalized cDNA library derived from the same stage of
      the parasite confirmed that both genes are expressed at least in the epimastigote
      stage of T. cruzi. Comparison of the putative T. cruzi proteins to their
      counterparts in other organisms revealed significant protein sequence
      conservation over large evolutionary distances. Computer analysis revealed the
      presence of several motifs in both proteins, possibly related to the regulation
      and localization of these proteins in the parasite.

PMID- 10964647
TI  - Strongyloides ratti: thermokinetic behavior of third-stage larvae on a
      temperature gradient.
AB  - We examined the thermokinetic behaviors of infective third-stage larvae (L3) of
      the rodent parasitic nematode Strongyloides ratti on temperature gradients using
      an in vitro agarose tracking assay method. Observed behaviors included both
      negative and positive thermokineses, the direction of movement depending both on
      the gradient temperature at which larvae were initially placed and on prior
      experience of culture temperature. Larvae isolated from rat feces cultured at 25
      degrees C and placed on a gradient at temperatures between 22 degrees and 29
      degrees C tended to move toward higher temperatures. At higher placement
      temperatures, most larvae moved little and showed no directional response,
      whereas at lower placement temperatures, many migrated toward cooler
      temperatures. At placement temperatures of 20 degrees C or below, few or no
      larvae moved toward the zone of higher temperature. Larvae isolated from rat
      feces cultured at 20 degrees C tended to migrate to a high temperature area
      regardless of placed temperature. Those cultured at 30 degrees C did not respond
      to the temperature gradient. L3 cultured at 30 degrees C were significantly less
      infective to rats than those cultured at 25 degrees or 20 degrees C. Additional
      experiments were designed to demonstrate thermokinetic behaviors during the
      period after reaching the L3 stage. Larvae incubated in double distilled water
      (DDW) for 24 h at 37 degrees C lost their ability to respond to lower
      temperatures, while in those incubated in DDW at 15 degrees and 25 degrees C,
      responses were still apparent. The thermokinetic behavior of S. ratti L3 is
      affected by surrounding environmental temperatures and this may have an important
      role in host finding.

PMID- 10964646
TI  - Plasmodium yoelii: effects of red blood cell modification and antibodies on the
      binding characteristics of the 235-kDa rhoptry protein.
AB  - The 235-kDa rhoptry protein of the rodent malaria parasite Plasmodium yoelii
      yoelii was shown to bind to the surface of mouse red blood cells in a calcium
      independent process, using a erythrocyte-binding assay. This binding is affected
      by modification of the surface of the red blood cells by enzymatic treatment.
      Chymotrypsin and trypsin but not neuraminidase treatment of the erythrocytes
      significantly reduced the binding of the 235-kDa proteins. The binding of an
      unrelated 135-kDa protein was abolished by treatment with chymotrypsin. Although
      the 235-kDa proteins bind to both reticulocytes and mature red blood cells, the
      binding to mature cells was more pronounced. In the presence of hyperimmune
      infection serum or specific polyclonal antibodies to the 235-kDa protein its
      binding to erythrocytes was reduced, further demonstrating the specificity of
      this ligand-receptor interaction.

PMID- 10964648
TI  - Development of brain injury in mice by Angiostrongylus cantonensis infection is
      associated with the induction of transcription factor NF-kappaB, nuclear
      protooncogenes, and protein tyrosine phosphorylation.
AB  - Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus
      cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand,
      and Japan. Although eosinophilia is an important clinical manifestation of A.
      cantonensis infection, the role of eosinophils in the progress of the infection
      remains to be elucidated. In this experiment, we showed that A. cantonensis
      caused eosinoplia and inflammation might lead to the induction of NF-kappaB and
      protooncogene expression via activation of the tyrosine phosphorylation signal
      pathway. After mice were infected daily with 30 third-stage larvae of A.
      cantonensis by oral adminstration for 6 weeks, no significant differences PKC
      alpha, MEK-1, ERK-2, JNK, and p38 protein expression were found between the
      control and infected mice. However, the protein tyrosine phosphorylation levels,
      NF-kappaB, and iNOS protein products were significantly increased by 3.5-, 3.3-,
      and 6.3-fold, respectively, after 3 weeks of A. cantonensis infection. The same
      pattern was found for c-Myc, c-Jun, and c-Fos proteins, which were elevated by
      3.2-, 2.3-, and 3.4-fold, respectively, compared to control animals after 3
      weeks. The expression potency of these proteins started increasing in week 1,
      reaching maximal induction in week 3, and then declining in week 5 after A.
      cantonensis infection. Another consistent result was noted in the pathological
      observations, including eosinophilia, leukocyte infiltration, granulomatous
      reactions, and time responses in brain tissues of infected mice. These data
      suggest that the development of brain injury by eosinophlia of A. cantonensis
      infection is associated with NF-kappaB and/or nuclear protooncogenes expression,
      which is activated by the tyrosine phosphorylation pathway.

PMID- 10964649
TI  - Leishmania infantum: stage-specific activity of pentavalent antimony related with
      the assay conditions.
AB  - The determination of the intrinsic sensitivity of Leishmania strains to
      pentavalent antimonials in clinical trials, before treatment is begun, is
      essential in order to avoid failures and to allow alternative drugs to be chosen.
      A comparative study of SbV activity on promastigotes, axenic amastigote-like
      cells, and intracellular amastigotes of Leishmania infantum, when administered in
      the form of meglumine antimoniate and free, in hydrochloric solution, was
      performed. Results indicate that the conditions under which the promastigotes
      were cultured affect the IC(50) obtained, although results were homogeneous when
      the products were assayed on axenic-like and intracellular amastigotes. The
      IC(50) obtained for SbV in the form of meglumine antimoniate or in hydrochloric
      solution on promastigotes cultured in Schneider's medium depends on the growth
      rate of the culture and therefore could be regulated by modifying the fetal calf
      serum concentration in the medium. The pH of the culture medium strongly affected
      the activity of meglumine antimoniate but not that of the SbV hydrochloric
      solution on promastigotes cultured in Schneider's medium. This influence of pH
      was observed to a much lesser extent when promastigotes were cultured on M199 or
      RPMI media. In homogeneous culture conditions, which included the regulation of
      the promastigote growth rate through the heat-inactivated fetal calf serum
      concentration in the medium and the dilution of the meglumine antimoniate with
      Schneider's medium at pH 6.5, the activity of SbV, free or in the form of
      meglumine antimoniate, was the same in promastigotes, intracellular amastigotes,
      and axenic amastigote-like cells.

PMID- 10964650
TI  - Plasmodium vivax: polymorphism in the merozoite surface protein 1 gene from wild
      Colombian isolates.
AB  - The Plasmodium vivax merozoite surface protein-1 (PvMSP-1) has been considered a
      candidate for a malaria vaccine against erythrocytic stages. PvMSP-1 is
      immunogenic during natural infections and exhibits antigenic polymorphism. The
      extent of genetic polymorphism in a region between the so-called interspecies
      conserved blocks (ICBs) 2 and 4 of the PvMSP-1 was analyzed in 20 isolates taken
      from patients from two different areas in Colombia. Variation is unevenly
      distributed along this gene segment among the isolates. Comparative analysis of
      these sequences led to the definition of five sequence types (ST1 to 5). ST1 to
      ST4 exhibit a variation pattern associated with sequences present in the Salvador
      or Belem sequences. However, ST5 has clusters of sequence that have not been
      previously described. The changes found along the five variants confirm the
      important role of recombinational and/or gene conversion events in generating
      allelic diversity.

PMID- 10964651
TI  - Plasmodium falciparum: generation of a cDNA library enriched in sporozoite
      specific transcripts by directional tag subtractive hybridization.
AB  - We have adapted the "directional tag subtractive hybridization" technique as a
      means of investigating stage-specific gene expression in Plasmodium falciparum.
      This technique utilizes unidirectional cDNA libraries cloned into separate lambda
      vectors and involves hydroxyapatite chromatographic separation of target
      antisense cDNA and driver sense strand cRNA followed by PCR amplification of cDNA
      sequences specific to the target stage. This technique enabled efficient
      subtraction of asexual blood stage sequences from a P. falciparum sporozoite cDNA
      library and led to identification of novel sporozoite sequences. This technique
      can be applied to study gene expression in parasite stages that are difficult to
      obtain routinely.

PMID- 10964653
TI  - Prion disease: A loss of antioxidant function?
AB  - Prion disease, a neurodegenerative disorder, is widely believed to arise when a
      cellular prion protein (PrP(C)) undergoes conformational changes to a pathogenic
      isoform (PrP(Sc)). Recent data have shown PrP(C) to be copper binding and that it
      acquires antioxidant activity as a result. This enzymatic property is dependent
      mainly on copper binding to the octarepeats region. In normal human brain and
      human prion disease, there is a population of brain-derived PrP that has been
      truncated at the N-terminal which encompassed the octarepeats region. Increasing
      evidences have suggested imbalances of metal-catalyzed reactions to be the common
      denominator for several neurodegenerative diseases. Therefore, we propose that
      one of the causative factors for prion disease could be due to the imbalances in
      metal-catalyzed reactions resulting in an alteration of the antioxidant function.
      These result in an increase level of oxidative stress and, as such, trigger the
      neurodegenerative cascade.

PMID- 10964652
TI  - Genetic markers for the parasitic nematode Haemonchus contortus based on intron
      sequences.

PMID- 10964654
TI  - Identification of the NAD(+)-binding fold of glyceraldehyde-3-phosphate
      dehydrogenase as a novel RNA-binding domain.
AB  - There is growing evidence that metabolic enzymes may act as multifunctional
      proteins performing diverse roles in cellular metabolism. Among these functions
      are the RNA-binding activities of NAD(+)-dependent dehydrogenases. Previously, we
      have characterized the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) as an RNA-binding protein with preference to adenine-uracil-rich
      sequences. In this study, we used GST-GAPDH fusion proteins generated by deletion
      mutagenesis to search for the RNA binding domain. We established that the N
      terminal 43 amino acid residues of GAPDH, which correspond to the first
      mononucleotide-binding domain of the NAD(+)-binding fold is sufficient to confer
      RNA-binding. We also provide evidence that this single domain, although it
      retains most of the RNA-binding activity, loses sequence specificity. Our results
      suggest a molecular basis for RNA-recognition by NAD(+)-dependent dehydrogenases
      and (di)nucleotide-binding metabolic enzymes that had been reported to have RNA
      binding activity with different specificity. To support this prediction we also
      identified other members of the family of NAD(+)-dependent dehydrogenases with no
      previous history of nucleic acid binding as RNA binding proteins in vitro. Based
      on our findings we propose the addition of the NAD(+)-binding domain to the list
      of RNA binding domains/motifs.

PMID- 10964655
TI  - Trafficking of human ADAM 12-L: retention in the trans-Golgi network.
AB  - We have investigated the trafficking of the membrane-anchored form of human ADAM
      12 (ADAM 12-L) fused to a green fluorescence protein tag. Subcellular
      localization of the protein in transiently transfected cells was determined by
      fluorescence microscopy and trypsin sensitivity. Full-length ADAM 12-L was
      retained in a perinuclear compartment, which was shown to be the trans-Golgi
      network. In contrast, ADAM 12-L lacking the cytoplasmic domain reached the cell
      surface. Based on analysis of deletions and mutations of the cytoplasmic tail of
      ADAM 12-L, the retention signal is comprised of both the cytoplasmic and
      transmembrane domains, but not the Src homology 3 domain (SH3) binding sites.
      These results raise the possibility that a trafficking checkpoint in the trans
      Golgi network is one of the cellular mechanisms for regulation of ADAM 12-L
      function, by allowing a rapid release of ADAM 12-L to the cell surface under
      specific stimuli.

PMID- 10964656
TI  - Involvement of nuclear factor-kappaB (NF-kappaB) signaling in the expression of
      inducible nitric oxide synthase (iNOS) gene in rat C6 glioma cells.
AB  - It has been demonstrated from studies using NF-kappaB inhibitors that NF-kappaB
      may be involved in the iNOS induction stimulated by cytokines and/or
      lipopolysaccharide (LPS) in various cell types and tissues. However, the actions
      of the inhibitors are less selective and highly cytotoxic. We constructed stable
      clones of C6 cells transfected with two types of IkappaBalpha mutant genes
      (IkappaBalpha(SS --> AA); Ser-32/36 to Ala-32/36, IkappaBalpha(KK --> RR); Lys
      21/22 to Arg-21/22). IkappaBalpha(SS --> AA) strongly inhibited (1) LPS-, IL
      1beta-, and TNF-alpha-induced nuclear translocation and DNA binding of NF-kappaB
      to the kappaB site; and (2) iNOS induction stimulated by LPS or IL-1beta plus IFN
      gamma. These results indicate that NF-kappaB plays a critical role in cytokines
      and/or LPS-induced iNOS induction. Surprisingly, similar to the endogenous
      IkappaBalpha, IkappaBalpha(KK --> RR) was degraded by various stimuli, and
      proteasome inhibitors blocked this event. These results suggest that another Lys
      residue(s), other than Lys-21/22, may be required for the ligand-induced
      IkappaBalpha degradation by the ubiquitin-proteasome pathway.

PMID- 10964657
TI  - Magnet used for protein crystallization: novel attempts to improve the crystal
      quality.
AB  - The accuracy of the structures of biological macromolecules determined by X-ray
      crystallography is of fundamental importance, both for the understanding of life
      processes and for medical applications. The resolution of the structure is thus
      critical, and is largely determined by the quality of single crystals. Here we
      report the results of applying a magnetic field and a magnetization force during
      growth of the snake muscle fructose-1,6-bisphosphatase and human estrogenic
      17beta-hydroxysteroid dehydrogenase crystals. For both enzyme proteins, the
      quality of the crystals improved with repeated assay, and their data sets were
      collected at significantly higher resolutions. These results coincide with a
      mechanism involving the reduction of convection, due to both the hydrodynamics
      within a magnet and the partially reduced gravity induced by a magnetization
      force. The density difference between the crystal and solution becomes less
      significant, and the sedimentation speed of the crystals is also reduced in the
      presence of the magnetization force.

PMID- 10964658
TI  - Biochemical characterization of cloned Aspergillus fumigatus phytase (phyA).
AB  - The gene for Aspergillus fumigatus phytase (phyA) was cloned and expressed in
      Pichia pastoris. The enzyme expressed was purified to near homogeneity using
      sequential ion-exchange chromatography and was characterized biochemically.
      Although A. fumigatus phytase shows 66.2% sequence homology with A. ficuum
      phytase, the most widely studied enzyme, the cloned phytase showed identical
      molecular weight and temperature optima profile to the benchmark phytase. The pH
      profile of activity and kinetic parameters, however, differed from A. ficuum
      phytase. The cloned enzyme contains the septapeptide RHGARYP motif, which is also
      identical to the active site motif of A. ficuum phytase. Chemical probing of the
      active site Arg residues using both cyclohexanedione and phenylglyoxal resulted
      in the inactivation of phytase. The cloned A. fumigatus phytase, however, was
      more resistant to phenylglyoxal-induced inactivation. Both cloned A. fumigatus
      and A. ficuum phytases were identically affected by cyclohexanedione. Both the
      thermal characterization data and kinetic parameters of cloned and expressed A.
      fumigatus phytase indicate that this biocatalyst is not superior to the benchmark
      enzyme. The sequence difference between A. fumigatus and A. ficuum phytase may
      explain why the former enzyme catalyzes poorly compared to the benchmark enzyme.
      In addition, differential sensitivity toward the Arg modifier, phenylglyoxal,
      indicates a different chemical environment at the active site for each of the
      phytases.

PMID- 10964659
TI  - Reducing agents and light break an S-S bond activating rhodopsin in vivo in
      Chlamydomonas.
AB  - Light induces retinal synthesis via photoactivation of a small amount of
      Chlamydomonas rhodopsin pigment (Foster et al., Proc. Natl. Acad. Sci. USA 85,
      6379-6383). A reducing agent [dithiothreitol (DDT) or mercaptoacetic acid (MAA)]
      also induces retinal synthesis in the dark via a rhodopsin with a chromophore. If
      the opsin is saturated with retinal and is bleached with light in the presence of
      a thiol trapping agent, the bleaching becomes irreversible. We conclude that the
      reducing agent as well as light break a disulfide bond resulting in activation of
      the rhodopsin and induction of carotenogenesis. Both the chemical and light
      induction is inhibited by GDPbetaS and pertussis toxin. Breaking the bridge
      between the 3rd and 5th helix may lead to increased proton accessibility of
      Asp134 leading to the rolling of the 3rd helix and MetaIIb formation.

PMID- 10964660
TI  - Regulation of ferritin mRNA translation in primary erythroblasts: exogenous c-Kit
      plus EpoR signaling mimics v-ErbA oncoprotein activity.
AB  - In general, translation efficiency of ferritin mRNAs is modulated by variations
      in iron supply. In primary avian erythroblasts undergoing short-term
      proliferation, however, ferritin heavy chain (ferH) mRNA is repressed at all iron
      levels. Yet, expression of v-ErbA oncoprotein is sufficient to reinduce ferH mRNA
      utilization at physiological iron concentrations. Since overexpression of the
      receptor tyrosine kinase c-Kit and erythropoietin receptor (EpoR) stimulates long
      term proliferation of primary erythroblasts like v-ErbA, we analyzed the impact
      of cooperation between c-Kit and EpoR on the regulation of iron storage. Whereas
      endogenous c-Kit in combination with exogenous EpoR had no significant effect,
      ectopic overexpression of both receptors abolished translational repression of
      ferH mRNA upon iron administration. Thus, high-intensity signaling through c-Kit
      plus EpoR pathways mimics the v-ErbA-mediated regulatory phenotype.

PMID- 10964661
TI  - Human leukocytes contain a large pool of free forms of CD18.
AB  - Monoclonal antibodies to CD18, the common chain of leukocyte integrins, recognize
      in various types of human lymphoid and myeloid cells under the conditions of
      nonreducing Western blotting three species of CD18 of mol. wt. 96, 87, and 78
      kDa, respectively. Using a unique monoclonal antibody MEM-148 reacts exclusively
      with free CD18 molecules, but not with leukocyte integrin heterodimers. We
      demonstrate that only the upper one (96 kDa) is present on the cell surface
      within the CD11/CD18 integrin heterodimers, while the lower ones (87 and 78 kDa)
      are found intracellularly as free molecules unassociated with CD11 chains or
      other molecules. These intracellular free CD18 chains may in part represent
      biosynthetic precursors; alternatively, these species may represent an
      intracellular source of the recently observed free, proteolytically truncated
      CD18 chains expressed on the surface of activated myeloid cells.

PMID- 10964662
TI  - Evidence for apoptosis in the selenite rat model of cataract.
AB  - The purposes of this experiment were (1) to determine if apoptosis was
      accelerated during formation of selenite cataract, and (2) to determine the role
      of calpains and caspases in lens apoptosis. Evidence for apoptosis in selenite
      injected rats included: approximately 7-8% of epithelial cells in germinative
      zone were positive, disappearance of the nuclear membrane, condensation of the
      chromatin, and breakdown of PARP. Activation of calpains was indicated by
      characteristic limited proteolysis of crystallins, breakdown of alpha-spectrin to
      150/145 kDa fragments, hydrolysis of vimentin, and autolytic breakdown of m
      calpain. Selenite cataract did not have an appreciable effect on the mRNA levels
      for caspase-3, calpains, and calpastatin. This indicated the increased enzyme
      activity of m-calpain and caspase-3 in selenite cataract occurred at the enzyme
      level rather than by upregulation of mRNAs. Increased calpain and caspase
      activity may be linked to the selenite-induced apoptosis. Such data are important
      because they indicate that apoptosis may be a fairly early event in selenite
      cataract.

PMID- 10964663
TI  - Oxidation of 7,8-dihydroneopterin by hypochlorous acid yields neopterin.
AB  - In vitro, interferon-gamma stimulates primate monocytes/macrophages to produce
      the pteridines neopterin and 7,8-dihydroneopterin. These pteridines are capable
      of modulating the oxidative potential of reactive species. Neopterin is pro
      oxidative whereas 7, 8-dihydroneopterin is an effective antioxidant. In the
      presence of oxygen, 7,8-dihydroneopterin is rapidly oxidized and after loosing
      the side chain 7,8-dihydroxanthopterin is formed. It is considered that under
      physiological conditions, 7,8-dihydroneopterin cannot be a source for neopterin
      production. In this study it is demonstrated that hypochlorous acid is capable to
      oxidize 7,8-dihydroneopterin yielding neopterin. Neopterin is less affected by
      hypochlorous acid, and in a mixture of both pteridines similar to the in vivo
      situation, only 7,8-dihydroneopterin is oxidized, thereby increasing the ratio
      towards neopterin. The findings may beat relevance for the in vivo situation
      since hypochlorous acid shifts the neopterin/7, 8-dihydroneopterin ratio towards
      the side of neopterin, hence probably increasing the oxidative potential in a
      micro-environment.

PMID- 10964664
TI  - Activation of protein kinase C inhibits the expression of connective tissue
      growth factor.
AB  - Connective tissue growth factor (CTGF) is a member of a protein family in which
      38 cysteine residues are conserved. Although a wide variety of important
      biological functions have been ascribed to these proteins in recent years, the
      regulation of their gene expression for most members is virtually unknown. We
      studied the effects of protein kinase C (PKC) and tyrosine kinase on the
      expression of CTGF and observed that at the mRNA level CTGF expression is
      inhibited by the activation of PKC, but stimulated by the inhibition of PKC and
      tyrosine kinase. We further determined that the novel and the classical PKC
      isoforms are needed for the inhibition, but the atypical isoforms are not
      involved. Our data suggest that phosphorylation on serine/threonine and tyrosine
      by PKC and by tyrosine kinase are all inhibitory to the expression of CTGF.

PMID- 10964665
TI  - Vasopressin V1a receptor signaling in a rat choroid plexus cell line.
AB  - A new cell line was derived from primary culture of rat choroid plexus (RCP) by
      immortalization with the TSOri minus adenovirus. The selected clone expressed
      vasopressin V1a receptors at a density of 64,000 sites per cell, and a K(d) of
      7.2 nM. Addition of vasopressin to the RCP cells induced a transient calcium peak
      comparable to V1a receptor signalling in different expression systems. This
      [Ca(2+)](i) increase was dose-dependent with an EC(50) of 22 nM vasopressin.
      Similar [Ca(2+)](i) increase was elicited by addition of serotonin, angiotensin
      II, endothelin-1, and bradykinin. Heterologous desensitization of V1a receptor
      was observed in RCP cells exposed to the phorbol ester PMA or following
      stimulation of other receptors coupled to the phosphoinositide pathway. Positive
      immunolabelling with Factor VIII, Flt1 and CD 34 antibodies suggests that this
      new RCP cell line originated from endothelial cells of rat choroid plexus.

PMID- 10964666
TI  - Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate.
AB  - Epidemiological, in vitro cell culture, and in vivo animal studies have shown
      that green tea or its constituent polyphenols, particularly its major polyphenol
      epigallocatechin-3-gallate (EGCG) may protect against many cancer types. In
      earlier studies, we showed that green tea polyphenol EGCG causes a G0/G1-phase
      cell cycle arrest and apoptosis of human epidermoid carcinoma (A431) cells. We
      also demonstrated that these effects of EGCG may be mediated through the
      inhibition of nuclear factor kappa B that has been associated with cell cycle
      regulation and cancer. In this study, employing A431 cells, we provide evidence
      for the involvement of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent
      kinase (cdk) machinery during cell cycle deregulation by EGCG. As shown by
      immunoblot analysis, EGCG treatment of the cells resulted in significant dose-
      and time-dependent (i) upregulation of the protein expression of WAF1/p21,
      KIP1/p27, p16 and p18, (ii) downmodulation of the protein expression of cyclin
      D1, cdk4 and cdk6, but not of cyclin E and cdk2, (iii) inhibition of the kinase
      activities associated with cyclin E, cyclin D1, cdk2, cdk4 and cdk6. Taken
      together, our study suggests that EGCG causes an induction of G1-phase ckis,
      which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle
      thereby causing a G0/G1-phase arrest of the cell cycle, which is an irreversible
      process ultimately resulting in an apoptotic cell death. We suggest that the
      naturally occurring agents such as green tea polyphenols which may inhibit cell
      cycle progression could be developed as potent anticancer agents for the
      management of cancer.

PMID- 10964667
TI  - Nitrite inhalation in rats elevates tissue NOS III expression and alters tyrosine
      nitration and phosphorylation.
AB  - Organic nitrites are nitric oxide (NO) donors that are used predominantly as
      inhalant drugs of abuse and have been shown to have immunomodulating effects. NO
      donors can modulate NOS activity and expression, thus altering the level of
      endogenous NO production. NO can react with superoxide (O(*)(2)(-)) to form
      peroxynitrite (ONOO(-)), which can nitrate tyrosine residues in proteins and
      alter tyrosine phosphorylation. We investigated the effects of inhaled isobutyl
      nitrite (ISBN) on NOS expression, tyrosine nitration, and tyrosine
      phosphorylation in selected organs of rats. Following exposures of 109 and 1517
      ppm ISBN for 4 h, the lung, spleen, liver, and kidney were removed and assayed by
      SDS-PAGE for NOS III (eNOS), NOS II (iNOS), nitrotyrosine (NT)- and
      phosphotyrosine (PT)-immunoreactive proteins using specific antibodies. ISBN at
      1517 ppm, but not 109 ppm, caused an increase in NOS III expression in the liver
      and kidney, but not in the lung and spleen. No apparent effect on NOS II
      expression was observed in these organs. The expressions of NT and PT protein
      bands (30-200 kDa) were increased in the liver and kidney, but not in the lung
      and spleen. This increase in NT persisted for 24 h post-exposure. Increased NOS
      III expression in the liver and kidney may promote peroxynitrite formation and
      contribute to the increase in NT and PT immunoreactivity. ISBN inhalation may
      thus cause changes in cellular signaling involving tyrosine phosphorylation.
      These findings may suggest a mechanistic basis for the apparent immunotoxicity
      associated with nitrite abuse.

PMID- 10964668
TI  - Characterization of two DNase gamma-specific monoclonal antibodies and the in
      situ detection of DNase gamma in the nuclei of apoptotic rat thymocytes.
AB  - Two novel monoclonal antibodies (mAbs), hg302 and hg303, raised against a
      synthetic peptide corresponding to the basic domain of human DNase gamma, are
      characterized in detail. In Western blot analysis, hg303 recognizes both wild
      type and C-terminal Myc-His-tagged human DNase gamma, but does not cross-react
      with human DNase I family members, DNase I, DNase X, or DNAS1L2. On the other
      hand, dot blot analysis reveals the fine specificity of hg302; it recognizes
      human, mouse, and rat DNase gamma, but not other DNase I family DNases under non
      denaturing conditions. Furthermore, hg302 efficiently immunoprecipitates wild
      type, but not C-terminal Myc-His-tagged, human DNase gamma from cell lysates. In
      immunohistochemical analysis, hg302 strongly recognizes DNase gamma in the nuclei
      of X-ray irradiation-induced apoptotic, but not normal rat thymocytes. The
      specific detection of DNase gamma in apoptotic nuclei is confirmed by indirect
      immunofluorescence analysis using TNF-alpha-induced apoptotic HeLa S3 cells
      transfected with DNase gamma. These results, together with the observations that
      DNase gamma is present in normal thymocytes and its activity is unchanged during
      the apoptosis, suggest that some molecular change(s), which triggers the
      activation of DNase gamma, occurs in response to apoptotic stimuli in the basic
      domain, and hg302 specifically recognizes the activated DNase gamma in
      immunohistochemical analysis.

PMID- 10964669
TI  - The pharmacology of a new nitric oxide donor: B-NOD.
AB  - We describe here a new compound, B-NOD, which, in vitro and in situ, releases
      nitric oxide (NO). Its activity in situ persists for more than 7 h, it does not
      cause a fall in blood pressure or an increase in heart rate and can be orally
      administered. It increases cyclic guanosine monophosphate (cGMP) and prevents
      platelet aggregation. In vitro, its release of NO is augmented by the presence of
      living cells (blood platelets). B-NOD may be useful in a number of clinical
      conditions in which prolonged release of NO without hemodynamic effects are
      desirable. A combination of aspirin with B-NOD could be formulated in which the
      individual concentrations of aspirin and B-NOD may be useful in the long-term
      treatment of coronary artery disease and in clinical situations in which long
      term release of NO may be beneficial.

PMID- 10964670
TI  - Human lens high-molecular-weight alpha-crystallin aggregates.
AB  - Alpha-crystallin high-molecular-weight (HMW) aggregates can be formed in vitro by
      many mechanisms, but the mechanism of in vivo aggregation has not been clearly
      established. HMW and LMW (low-molecular-weight) alpha-crystallins were isolated
      from human lenses 50-60 years of age and some spectroscopic measurements were
      performed. Conformational differences were suggested based on data of increased
      bis-ANS (4,4'-dianilino-1,1'-binaphthalene-5, 5'-disulfonic acid) and ThT
      (thioflavin T) fluorescence as well as increased far-UV and decreased near-UV
      circular dichroism (CD). These results indicated that HMW alpha-crystallin was
      more hydrophobic than LMW alpha-crystallin, possibly resulting from partial
      unfolding of alpha-crystallin. On the other hand, the increased ThT fluorescence
      and far-UV CD intensities indicate that an increased amount of beta-sheet
      conformation was involved in aggregation. These data, along with little
      difference in chaperone-like activity between the LMW and HMW alpha-crystallins,
      strongly suggest that HMW alpha-crystallin aggregates resulted from partial
      unfolding and disassembling-reassembling of LMW alpha-crystallin caused by
      posttranslational modification rather than chaperone complex formation.

PMID- 10964671
TI  - Molecular mechanisms for antibody-mediated modulation of peptide-displaying
      enzyme sensors.
AB  - The generation of molecular sensors based on peptide-displaying enzymes for the
      detection of antibodies or antigens represents an innovative field of protein
      engineering. The knowledge of the underlying molecular mechanisms of enzymatic
      modulation in such sensors would be of great importance for the rational
      construction and improvement of responsiveness of new peptide-enzyme molecules.
      Here we analyze the enzymatic characteristics of three different kinds of sensors
      based in engineered beta-galactosidase, alkaline phosphatase and beta-lactamase,
      to explore a common activation basis. We describe two different categories of
      enzyme sensors. In one of them, including only some modified beta-lactamases, the
      enzymatic activity is inhibited upon ligand binding and it seems to be caused by
      the steric coverage of the active site by the bound antibody. In a second group,
      embracing members of the three studied enzymes, the ability to be modulated upon
      effector binding depends on the ratio between the k(cat) of the engineered enzyme
      and the k(cat) of the intact enzyme. This proves a common mechanism for enzymatic
      modulation of enzyme biosensors that is probably caused by conformational effects
      induced by the bound antibody on the enzyme.

PMID- 10964672
TI  - Differential expression of LR11 during proliferation and differentiation of
      cultured neuroblastoma cells.
AB  - An involvement of the low density lipoprotein receptor (LDLR) gene family in both
      intracellular signal pathways for neural organization and metabolic pathways for
      lipoprotein homeostasis is now well established. The discovery of LR11, a mosaic
      LDLR family member offers the opportunity to gain new insights into receptor
      multifunctionality. Here, we studied the proliferation-dependent expression of
      LR11 mRNA and protein using two cultured cell lines, IMR32 neuroblastoma and PC12
      pheochromocytoma. Within 24 h, the LR11 protein rose 1.9-fold in proliferating
      IMR32 cells, and increased further to 5.3-fold at 72 h. This conformed with a
      transcript level increase of 4.7-fold at 72 h in the proliferating cells. On the
      other hand, under differentiation conditions, a 2.9-fold increase was observed
      within 24 h, but at 72 h thereafter the protein levels decreased to 60% of
      control. The transcript also increased to 1. 8-fold within 24 h, and then
      decreased to 1.1-fold at 72 h. In order to assess the transcriptional activities
      of the LR11 gene, we identified the 5'-flanking region of the murine LR11 gene.
      Transfection of IMR32 and PC12 cells with plasmids containing the whole or
      deleted fragments of 5'-flanking region showed that element(s) responsible for
      the above described different transcriptional activities are located in the
      upstream sequence between -861 and -396. Thus, the transcription of LR11 in these
      two cell systems is regulated differently during proliferation and
      differentiation, suggesting that the multifunctionality of LR11, as well as other
      LDLR family members, for rapid cell growth in malignant cells and neural
      outgrowth in cultured neurons, respectively. The possible involvement of LR11 in
      cellular proliferation and differentiation sheds new light on its functions in
      neurons, malignant, and vascular cells.

PMID- 10964673
TI  - Molecular characterization of key diphtheria toxin:receptor interactions.
AB  - The major amino acids necessary for diphtheria toxin (DT) binding to its receptor
      have been identified previously. Studies by W. H. Shen et al. (J. Biol. Chem.
      269, 29077-29084, 1994) and by J. H. Cha et al. (Mol. Microbiol. 29 (5), 1275
      1284, 1998) suggested that the positively charged nature of the single amino acid
      residue, (516)Lys of DT, is crucial for binding to the DT receptor, whereas the
      negatively charged (141)Glu of the DT receptor is the most important residue for
      toxin binding. Here, we hypothesize that key interactions occur between these two
      oppositely charged amino acid residues. Reciprocal substitution of the residues
      at these positions between the toxin and the receptor was performed, which
      resulted in a partial reconstitution of the toxin:receptor interaction. This
      study provides the first biological data that characterizes the specific
      interaction of these two key residues with each other and also the additional
      interactions between other positively charged residues of DT and (141)Glu of the
      DT receptor.

PMID- 10964674
TI  - Loss of cell viability by histidine substitution of leucine 325 of the glutamate
      transporter EAAT1.
AB  - Although glutamate transporters and neutral amino acid transporters have 55%
      amino acid identity in the transmembrane domains, many residues are still unique
      to individual transporters, providing for structural stability or substrate
      binding. In this study, the mutant protein L325H, which replaced a leucine 325 of
      the glutamate transporter EAAT1 by a histidine, was evaluated. When expressed in
      Xenopus oocytes, L325H caused oocytes to weaken pigmentation in the animal pole,
      accompanied by patches of colorless spots. Oocytes finally oozed cytoplasm. The
      resting membrane potential in L325H oocytes was -18.9 +/- 2.5 mV, significantly
      more positive than -37.3 +/- 2.5 mV of oocytes expressing EAAT1. The holding
      current at -60 mV was 283.1 +/- 48.3 nA in L325H oocytes and 92.2 +/- 12.6 nA in
      EAAT1 oocytes. These results suggest that even though glutamate and neutral amino
      acid transporters have strong overall homology, the local structure in the
      transmembrane domains may be different.

PMID- 10964675
TI  - Structure-activity studies on mammalian adenosine kinase.
AB  - The structure-activity relationship for Chinese hamster adenosine kinase (AK) was
      examined by making systematic deletions from the N- and C-terminal ends. The
      first 16 a.a. residues from the N-terminal end, which likely form a random coil,
      can be deleted without any effect on AK activity or stability. The successive
      removal of the next 11 residues, which stabilize the first beta structure of the
      protein, leads to a progressive loss of AK activity from 100 to about 3%. The
      loss in activity is accompanied by increasing thermal instability and a slight
      increase in the K(m) for adenosine. All deletions beyond residue M28, which
      should cause disruption of the tertiary structure, are devoid of AK activity. The
      residues at the C-terminal end form a substructure involved in the stability of
      the "adenosine 2 binding site" and removal of any residues results in significant
      loss of activity. Successive removal of the first 10 residues from this end
      causes progressive decrease in AK activity to about the 2% level, accompanied by
      a five-fold increase in the K(m) for ATP, supporting the view that the adenosine
      2 binding site located near the C-terminal end is the ATP binding site. All
      deletions beyond residue R348, which forms two salt bridges with the ATP binding
      site, are inactive. Site-directed replacement of an aspartic acid residue (D316),
      which is postulated to function in the transfer of phosphate from ATP to
      adenosine by either asparagine or glutamic acid, leads to complete loss of
      activity, supporting the proposed role of D316 as the catalytic base.

PMID- 10964676
TI  - Molecular cloning and characterization of a copper chaperone for copper/zinc
      superoxide dismutase from the rat.
AB  - Copper chaperone is an essential cytosolic factor that maintains copper
      homeostasis in living cells. Cytosolic metallochaperones have been recently
      identified in plant, yeast, rodents, and human cells. During our investigation,
      we found a new member of the copper chaperone family for copper/zinc superoxide
      dismutase, which was cloned from rats. The new copper chaperone was named rCCS
      (rat Copper Chaperone for Superoxide dismutase). The cDNA of rCCS was found to
      have a length of 1094 bp, and the protein analyzed from the cDNA was deduced to
      contain 274 amino acids. The amino acid sequence of rCCS consists of three
      domains: A metal binding domain, which has a MXCXXC motif in domain I, a homolog
      of the Cu/Zn SOD in domain II, and a CXC motif in domain III. The binding of rCCS
      to Cu/Zn SOD was analyzed by GST column binding assay, and the domain II of rCCS
      was found to be essential for binding to Cu/Zn SOD, which in turn activates Cu/Zn
      SOD.

PMID- 10964677
TI  - Evaluation of dipeptide alpha-keto-beta-aldehydes as new inhibitors of cathepsin
      S.
AB  - A series of dipeptidyl alpha-keto-beta-aldehydes (glyoxals), prepared by solid
      /solution-phase chemistries, were assessed for their inhibitory activity against
      cathepsin S, a lysosomal cysteine protease implicated in a number of important
      pathophysiological processes. The inhibitor Cbz-Phe-Leu-COCHO, which exhibits
      slow-binding kinetic characteristics, was found to be almost 400-fold more
      selective for cathepsin S (K(i) = 0.185 nM) than for cathepsin B (76 nM) and is,
      to our knowledge, the most potent, reversible, synthetic cathepsin S inhibitor
      reported to date.

PMID- 10964679
TI  - Naturally occurring anti-band 3 antibody binds to apoptotic human T-lymphoid cell
      line Jurkat through sialylated poly-N-acetyllactosaminyl saccharide chains on the
      cell surface.
AB  - Human T-lymphoid cell line Jurkat was treated with actinomycin D (ActD) and
      cycloheximide (CHX). The induction of apoptosis was confirmed by the chromatin
      condensation and DNA ladder fragmentation. Anti-band 3 IgG, purified from normal
      human plasma, bound to the ActD- or CHX-treated cells, and the binding was
      correlated to the degree of apoptosis. Antioxidants, N-acetylcysteine,
      pilloridine dithiocarbamate, and trolox, inhibited neither induction of DNA
      fragmentation of ActD-treated cells nor anti-band 3 IgG binding to ActD-treated
      cells, indicating that formation of the anti-band 3 IgG binding sites on the
      apoptotic cell surface is caused by nonoxidative mechanism. When Jurkat cells
      were treated with endo-beta-galactosidase to cleave sialylated poly-N
      acetyllactosaminyl saccharide chains from the cell surface before induction of
      apoptosis, the binding of anti-band 3 IgG was abolished. The results indicate
      that sialylated poly-N-acetyllactosaminyl saccharide chains on the cell surface
      are requisite for the binding of anti-band 3 IgG to apoptotic cells.

PMID- 10964678
TI  - Repression of TNF-alpha-induced E-selectin expression by PPAR activators:
      involvement of transcriptional repressor LRF-1/ATF3.
AB  - Peroxisome proliferator-activated receptor (PPAR) activators were shown to
      inhibit the expression of E-selectin of human vascular endothelial cells in
      response to tumor necrosis factor-alpha (TNF-alpha). Troglitazone, pioglitazone,
      alpha-clofibrate, and 15-deoxy-Delta12,14-prostaglandin J2 all inhibited the TNF
      alpha-stimulated E-selectin gene transcription in reporter assay. To further
      clarify the underlying transcriptional regulation, nuclear factor(s) that binds
      to the nuclear factor-endothelial leukocyte adhesion molecule 1 (NF-ELAM1) site
      of the E-selectin gene promoter was investigated. The activators caused a
      significant induction of liver regenerating factor 1 (LRF1)/activating
      transcription factor 3 (ATF3), which bound to the NF-ELAM1 site and repressed the
      TNF-alpha-induced E-selectin gene expression. From these data, the effect of PPAR
      activators was mediated, in part, through the induction of LRF1/ATF3. This might
      provide a novel molecular mechanism of anti-inflammatory effect of PPAR
      activators.

PMID- 10964680
TI  - Upregulation of myosin heavy chain MHClalpha in rat muscles after unweighting and
      clenbuterol treatment.
AB  - Myosin heavy chain (MHC) mRNA isoforms were quantified in soleus (SOL) and
      gastrocnemius (GAS) muscles from rats exposed to 14 days of either hindlimb
      unweighting (HU), clenbuterol treatment (CB), or HU combined with CB treatment
      (HU-CB). All conditions induced in SOL a shift from slow to faster MHC mRNA
      isoforms and an upregulation of MHClalpha. Increases were highest with CB, lowest
      with HU-CB, and coincided mainly with elevations in MHClla mRNA isoforms. The
      changes in MHC mRNA levels in GAS muscle corresponded to fast-to-faster
      transitions. Elevations in MHClalpha mRNA were smaller than in SOL and seemed to
      occur in parallel with decreases in MHClbeta. Taken together, our results
      suggested that MHClalpha is expressed in transforming rat slow and fast muscles,
      most likely as an intermediate step between MHClbeta and MHClla.

PMID- 10964681
TI  - Regulation of insulin-like growth factor binding protein-5 mRNA abundance in rat
      intestinal smooth muscle.
AB  - IGF-I increases abundance of IGFBP-5 mRNA in rat intestinal smooth muscle cells
      (RISM), and IGFBP-5 protein in RISM conditioned media. The translational blocker,
      cycloheximide, decreased the abundance of IGFBP-5 mRNA to undetectable levels,
      suggesting that IGFBP-5 mRNA integrity is linked to protein synthesis. We studied
      the mechanism of IGF-I's effect on IGFBP-5 mRNA, and the role of cytoplasmic
      proteins in modulating IGFBP-5 mRNA abundance. Anisomycin, emetine, and puromycin
      abolished IGFBP-5 mRNA as seen with cycloheximide. Cycloheximide had a dose- and
      time-dependent effect on IGFBP-5 mRNA. IGF-I increased IGFBP-5 nuclear
      transcripts by reverse transcription-polymerase chain reaction (RT-PCR),
      suggesting that IGF-I acts at least partially by increasing IGFBP-5 mRNA
      transcription. Protein synthesis inhibitors did not affect IGFBP-5 nuclear
      transcripts, therefore, they affect only mature mRNA. The IGFBP-5 mRNA 3' and 5'
      UTRs were cloned and their sequences searched for adenosine-uridine rich elements
      (AUREs), elements shown to regulate RNA stability. RNA mobility gel shift assay
      showed two protein activities that bind to nt 922 to 2076 of the 3' UTR, a region
      that contains an AURE. One protein activity (BA2) was decreased in cytoplasmic
      extracts from cycloheximide-treated RISM. These data demonstrate that IGFBP-5
      mRNA integrity is dependent on protein synthesis. The 3' UTR of IGFBP-5 contains
      elements shown to bind proteins important for RNA stability regulation. This
      region binds RISM cytoplasmic proteins, and may mediate the dramatic effect of
      cycloheximide on IGFBP-5 abundance. RNA-protein interactions may be important to
      IGFBP-5 mRNA stability and ultimately, to IGFBP-5 actions.

PMID- 10964682
TI  - Role of residues 230 and 236 of actin in myosin-ATPase activation by actin
      tropomyosin.
AB  - The Dictyostelium/Tetrahymena-chimeric actin (Q228K/T229A/A230Y) showed higher
      Ca(2+)-activation of myosin S1 ATPase in the presence of tropomyosin-troponin.
      The crystal structure of the chimeric actin is almost the same as that of wild
      type except the conformation of the side chain of Leu236. Here, we introduced an
      additional mutation (L236A), in which the side chain of Leu236 was truncated,
      into the chimeric actin (Q228K/T229A/A230Y/L236A). Without regulatory proteins,
      the new mutant actin showed normal myosin S1 activation and normal sliding
      velocity. However, in the presence of tropomyosin, the new mutant actin activated
      myosin S1 ATPase higher than the wild-type actin and showed higher velocities in
      in vitro motility assay at low HMM concentrations. These results suggest that the
      mutations of A230Y and L236A in the actin subdomain-4 facilitate the transition
      of thin filaments from a "closed" state to an "open" state.

PMID- 10964683
TI  - Biochemical characterization of casein kinase II as a protein kinase responsible
      for stimulation of HIV-1 protease in vitro.
AB  - The physiological significance of casein kinase II (CK-II) on the protease (PR)
      activity of recombinant HIV-1 PR (rPR) was biochemically investigated in vitro.
      We found that (i) the purified rPR (p11) functions as a phosphate acceptor of CK
      II; (ii) the PR activity of rPR is stimulated approximately 2.9-fold after its
      full phosphorylation by recombinant human CK-II (rhCK-II) in a manner similar to
      that observed for recombinant HIV-1 reverse transcriptase (rRT); and (iii) this
      stimulation is completely inhibited by two polyphenol-containing anti-oxidant
      compounds [quercetin and epigallo-catechin gallate (EGCG)] at 0.1 microM or a
      glycyrrhetinic acid derivative (oGA) and catechin at 10 microM without
      significant effect on the PR activity of rPR. These results suggest that (i) CK
      II may be a host mediator responsible for stimulation of PR and RT in HIV-1
      infected cells; and (ii) the selective inhibition of the CK-II-mediated
      stimulation of HIV-1 PR and RT by potent CK-II inhibitors may be involved in
      their anti-HIV-1 effects at the cellular level.

PMID- 10964684
TI  - Differential expression of the LAMB3 and LAMC2 genes between small cell and non
      small cell lung carcinomas.
AB  - To identify genes differentially expressed between small cell lung carcinoma
      (SCLC) cells and non-SCLC cells, mRNA differential display was applied to 3 SCLC
      cell lines and 6 non-SCLC cell lines. The LAMB3 gene was identified as being
      expressed only in non-SCLC cells and not in SCLC cells. The LAMB3 gene encodes
      the laminin beta3 chain, which is a unique component of laminin-5. Laminin-5 is a
      heterotrimer protein consisting of the alpha3, beta3, and gamma2 chains, and
      another unique component of laminin-5 is the gamma2 chain encoded by the LAMC2
      gene. RT-PCR analysis of the LAMB3 and LAMC2 genes in 45 lung cancer cell lines
      revealed that both the LAMB3 and LAMC2 genes were co-expressed in 21 of 32 non
      SCLC cell lines (66%) but only in one of 13 SCLC cell lines (8%). Coexpression of
      the LAMB3 and LAMC2 genes was also observed in all 4 cases of primary non-SCLC
      cells examined but not in the corresponding non-cancerous lung cells. Since
      alpha6beta4 integrin, the specific laminin-5 binding receptor, is known to be
      expressed only in non-SCLC cells and not in SCLC cells, it was indicated that
      laminin-5 is a critical microenvironmental factor for the growth of non-SCLC
      cells but not of SCLC cells. The differences in the expression of integrins and
      laminins would be critical factors to distinguish SCLC and non-SCLC cells, and
      such differences might be associated with the unique biological properties of
      SCLC cells, including metastatic potential and drug sensitivity.

PMID- 10964685
TI  - CD36 is a ditopic glycoprotein with the N-terminal domain implicated in
      intracellular transport.
AB  - The CD36 receptor sequence predicts two hydrophobic domains located at the N- and
      C-termini of the protein, but there are conflicting reports as to whether the N
      terminal uncleaved leader sequence functions as a transmembrane domain. To
      investigate the topology of CD36, we generated a panel of mutants lacking either
      one or both hydrophobic regions and analyzed their folding and transport in COS-7
      cells. The N- and the C-terminal hydrophobic regions were both sufficient to
      anchor CD36 in the membrane, and a FLAG epitope inserted at the N-terminus was
      located intracellularly. These results indicate that CD36 adopts a ditopic
      configuration. Accordingly, neither N- nor C-terminal truncation mutants were
      secreted. Analysis with conformation-specific monoclonal antibodies showed that
      the N-terminal transmembrane domain truncated molecule was slowly transported
      through the exocytic pathway and largely accumulated intracellularly. Thus, dual
      membrane insertion dictates the correct topogenesis and seems to be necessary for
      efficient folding and intracellular transport.

PMID- 10964686
TI  - Expression of transcriptional repressor proteins mSin3A and 3B during aging and
      replicative senescence.
AB  - Sin3 proteins have a key role in transcriptional repression mediated by histone
      deacetylation. Mammalian Sin3 proteins, mSin3A and 3B, act as adapter molecules
      which bind both to repressive transcription factors and to the methyl-CpG-binding
      proteins (MeCPs) and recruit histone deacetylases to assemble a multiprotein
      repressor complex. We have recently observed (Biochem. Biophys. Res. Commun. 252,
      274-277, 1998) that the expression of mSin3A but not mSin3B protein is induced
      during neuronal apoptosis. The purpose of this study was to find out whether
      aging and replicative senescence affect the expression levels of mSin3A and 3B
      repressor proteins. We studied the expression levels of mSin3A and 3B mRNAs and
      proteins both in replicative senescence model of WI-38 fibroblasts and in liver
      and brain tissues of young (4-6 months) and old (26-30 months) male Wistar rats.
      Replicative senescence of human WI-38 fibroblasts did not affect the expression
      levels of mSin3A and 3B mRNAs. However, the late passage WI-38 fibroblasts showed
      a significant decline in the expression level of mSin3A protein. Immortalization
      of WI-38 fibroblasts with SV-40 transformation increased the expression level of
      6.0 kb mSin3A mRNA. Aging of Wistar rats did not affect the expression levels of
      either mSin3A or mSin3B mRNAs in the liver and frontal cortex. Similarly, the
      protein levels of mSin3A and 3B were unaffected in the hippocampus, cerebellum
      and liver tissues during aging. These results show that aging in vivo, in
      contrast to replicative senescence, does not affect the expression levels of
      mSin3A and 3B repressor proteins. However, this does not exclude the possible age
      related functional changes mediated by mSin3-histone deacetylase complexes.

PMID- 10964687
TI  - The effect of valine substitution for glycine in the dimer interface of citrate
      synthase from Thermoplasma acidophilum on stability and activity.
AB  - To determine the role of hydrophobic interactions in the dimer interface of
      citrate synthase (CS) from Thermoplasma (Tp) acidophilum in thermostabilization,
      we have used site-directed mutagenesis to replace Gly 196 by Val on the helix L
      of the subunit interface. Recombinant wild-type and Gly 196 mutant TpCS enzymes
      were largely identical in terms of substrate specificities (K(m) for oxaloacetate
      and acetyl CoA). However, the mutation not only reduced catalytic activity (about
      10-fold) (i.e., V(max), k(cat) and specific activity) of the TpCS, but also
      decreased its thermal and chemical stability. Archaeal citrate synthase is active
      as a dimer, since residues from both monomers participate in the active site. Our
      results suggest that Gly196 --> Val mutation interferes with dimerization, so
      that improper dimerization or dissociation of the dimer would have a profound
      affect on the activity as well as the conformational stability of TpCS.

PMID- 10964688
TI  - Detection of MRP1 mRNA in human tumors and tumor cell lines by in situ RT-PCR.
AB  - The detection of the multridrug resistance-associated proteins is becoming
      increasingly important in assessing tumor sensitivity to treatment. In this work
      we describe a new, rapid, sensitive, and robust method for the detection of MRP1
      expression based on direct RT-in situ-PCR technology and fluorochrome-modified
      (dCTP(Cy3)) nucleotides. MRP1 expression was found in both placenta (BeWo) and
      liver (Hep G2)-derived tumor cell line as well as in small cell lung carcinoma.
      In liver-derived cells, MRP1 expression was detected by RT-in situ-PCR but not by
      in situ hybridization, suggesting a higher sensitivity of in situ amplification
      for the low level of expression in Hep G2 cells. RT solution PCR confirmed the
      presence of MRP1 in BeWo and Hep G2 cells, although the level of the gene
      expression was lower in liver cells. This method represents a viable alternative
      to conventional immunohistochemistry, and may be useful in the evaluation of MRP1
      expression in different tissue or cell lines.

PMID- 10964689
TI  - Gene expression of neurotrophins and their receptors in lead nitrate-induced rat
      liver hyperplasia.
AB  - Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF), and neurotrophin-3 (NT-3) are known to play important roles in the
      survival, proliferation, differentiation, and/or maintenance of function in
      several tissues including neuronal tissues. The role of neurotrophins in liver
      tissue, however, has not yet been clarified. In the present study, we assessed
      the temporal change in gene expression of neurotrophins, NGF, BDNF, and NT-3, and
      their receptors, low affinity neurotrophin receptor (p75NTR) and Trks A, B, and
      C, by RT-PCR technique in the liver of rats treated with lead nitrate (LN; 0.1
      mmol/kg body weight), an inducer of liver hyperplasia. The mRNAs for NGF, BDNF
      with exon 4, NT-3, p75NTR, and all Trk members were detected in the LN-untreated
      liver. LN treatment resulted in increases in the levels of NGF, BDNF with exon 4,
      NT-3, p75NTR, and TrkA mRNAs and further led to expression of BDNF mRNA with exon
      3. The increase in gene expression of neurotrophins and their receptors was
      closely correlated with those in liver weight. In this report, we propose for the
      first time that neurotrophins may play crucial roles in LN-induced liver
      hyperplasia.

PMID- 10964691
TI  - Microenvironment of cysteine 242 in type-1 ribosome-inactivating protein from
      iris.
AB  - IRIP is a type-1 ribosome-inactivating protein isolated from the bulbs of Iris
      hollandica. It is one of the few type-1 RIPs that contain Cys residue(s) in their
      primary sequence. IRIP contains a single Cys residue at position 242. Although
      IRIP is thought to be a monomeric protein, SDS-PAGE indicates that part of the
      IRIP molecules can exist as disulphide bridge-linked dimers. Probing of the
      reactivity of the unique Cys residue by 5, 5'-dithiobis(2-nitrobenzoic acid)
      indicates that Cys(242) in IRIP is free but is only partially accessible to
      modifiers. Molecular modelling of IRIP is in agreement with this conclusion.
      Binding of the ligands adenine and poly(A) results in little or no effect on the
      conformation of Cys(242) in IRIP. Chemical modification of IRIP by a specific
      thiol modifier does not abolish the RNA N-glycosidase activity of IRIP,
      suggesting that Cys(242) is not critical for the enzymatic activity of IRIP.
      These results suggest that IRIP has the potential to be developed as a novel
      immunotoxin.

PMID- 10964690
TI  - Central effects of a novel acylated peptide, ghrelin, on growth hormone release
      in rats.
AB  - Ghrelin, a novel growth-hormone-releasing acylated peptide, was recently isolated
      from rat stomach by the search of an endogenous ligand to an "orphan" G-protein
      coupled-receptor. Ghrelin neuron is present in the arcuate nucleus of rat
      hypothalamus, but its central effect on growth hormone (GH) release has yet to be
      clarified. We determined the plasma GH concentration and GH mRNA level in the
      pituitary in response to central administration of ghrelin. A single
      intracerebroventricular (ICV) administration of ghrelin to rats increased the
      plasma GH concentration dose-dependently. A continuous ICV administration of
      ghrelin via osmotic pump for 12 days increased the plasma GH concentration on day
      6, but did not keep the high GH concentration on day 12. The GH mRNA levels in
      both groups of single and continuous administration of ghrelin were not
      significantly different from those of controls. A single administration of growth
      hormone secretagogue also did not stimulate GH synthesis. Central ghrelin
      stimulated GH release but did not augment GH synthesis. In addition to gastric
      ghrelin, hypothalamic ghrelin functions to regulate GH release.

PMID- 10964692
TI  - Active allele loss of the androgen receptor gene contributes to loss of androgen
      receptor expression in female breast cancers.
AB  - Given the importance of androgen and androgen receptor (AR) in the control of
      female breast growth and the potential association with female breast cancer, we
      evaluated the AR expression in 114 female breast cancers and further analyzed why
      AR expression was lost. Immunohistochemical analysis revealed that 14.1% (17/114)
      of the tumors lost the AR expression completely. To unravel the molecular
      mechanism for AR expression loss, we first analyzed the somatic mutations in
      exons 2 through 8 of the AR gene by PCR-SSCP, but no mutation was detected. As
      the CAG repeats within exon 1 are also microsatellite markers, we then analyzed
      whether allelic loss was present. Interestingly, 11 of the 17 AR-negative tumors
      were heterozygous and 9 of them showed allelic loss. The lost allele was further
      demonstrated to be the active one by X-chromosome inactivation analysis. To
      confirm the immunohistochemical results, Northern and Western blot hybridization
      was performed and neither AR mRNA nor protein was detected in these AR-negative
      tumors. Loss of the active AR allele was strongly correlated with the AR
      expression loss (P = 0.0005). We conclude that AR expression loss is attributed
      to the active allele loss of AR gene in female breast cancers. Our finding may be
      also crucial in predicting and influencing the response of breast cancer to
      endocrine therapy.

PMID- 10964693
TI  - cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2:
      its mRNA expression, subcellular distribution, and chromosomal localization.
AB  - We isolated a human cDNA encoding a novel member of the bHLH-PAS transcription
      factor superfamily, BMAL2, which is highly similar to, but distinct from, BMAL1.
      The composite cDNA covered a 1720-bp sequence consisting of a putative 1653-bp
      open reading frame encoding a polypeptide of 551 amino acids. The deduced BMAL2
      product contains a bHLH-PAS domain in its N-terminal region and a variable C
      terminus. The overall identity of BMAL2 polypeptide to that of human BMAL1 is
      49%. RNA analysis revealed that expression of BMAL2 transcripts was restricted to
      the fetal brain and to the adult liver in human, while human BMAL1 mRNA was
      expressed in the brain and skeletal muscle. The chromosomal localization of the
      human BMAL2 gene was determined by fluorescent in situ hybridization to be
      localized on chromosome 12 at region p12.2-p11.2. These results suggest that
      BMAL2 may play different roles from BMAL1 in the embryonic brain and in adult
      mammals.

PMID- 10964694
TI  - Characterization of a novel member of the FGFR family, HrFGFR, in Halocynthia
      roretzi.
AB  - The cDNA for a novel member of the FGFR family, named HrFGFR, was isolated from a
      Halocynthia roretzi cDNA library prepared at the mid-tailbud stage. This cDNA was
      3507b long, and the deduced amino acid sequence contained a motif characteristic
      of the vertebrate FGFRs. The existence of a single copy of the FGFR homologue
      gene in H. roretzi was suggested by restriction site analysis of multiple clones.
      HrFGFR mRNA was expressed strongly in the posterior region in the epidermis from
      the middle neurula stage. By contrast, Xenopus FGFR homologues are expressed in
      the anterior region and are known to induce anterior neural formation. A
      transition of the region expressing FGFR might have induced the more complicated
      brain or head formation characteristic of vertebrates.

PMID- 10964696
TI  - Highly reactive cysteine residues in rodent hemoglobins.
AB  - Two hemoglobins with cysteine residues highly reactive toward electrophiles have
      been identified and characterized. Cys-125beta of guinea pig hemoglobin has a low
      pK(a) and forms conjugates with electrophiles more quickly than glutathione and
      several orders of magnitude more quickly than other protein thiols. This cysteine
      is capable of intercepting benzoquinone, a known carcinogenic metabolite, before
      other protein nucleophiles can be modified. Cys-13beta of mouse hemoglobin was
      observed to conjugate with electrophiles as quickly as glutathione. The
      structural basis of reactivity is different in the two hemoglobins and is
      analyzed in terms of hydrogen-bonding, solvent accessibility, and helix-dipole
      contributions. Complementing a previously characterized highly reactive cysteine
      in rat hemoglobin, identification of these cysteines suggests that the reactivity
      of these hemoglobins could represent a common function as a detoxification sink
      against carcinogens.

PMID- 10964695
TI  - Mouse prenylated Rab acceptor is a novel Golgi membrane protein.
AB  - We have cloned a mouse prenylated Rab acceptor (mPRA), which interacts with
      various Rab proteins in the yeast two-hybrid system. This study investigated its
      intracellular localization and characterized the localization signal. The mPRA
      was found to be an integral membrane protein that was localized to the Golgi
      complex at steady state as determined by confocal fluorescence microscopy. With
      green fluorescent protein attached to the N-terminus of mPRA, the fusion protein
      was expressed in BHK cells and was shown to exhibit the same Golgi localization
      as the native mPRA. Systematic truncations from the N- and C-termini of mPRA
      revealed that the entire N-terminal half (91 residues) of the protein was
      dispensable for the Golgi localization. In contrast, deletion of only 5 residues
      from the C-terminus diminished the Golgi localization of mPRA, leading to its
      accumulation in the ER. The data indicate that the C-terminal half (94 residues)
      of mPRA is necessary and sufficient for proper folding, ER export, and Golgi
      localization. The Golgi localization of mPRA suggests that it may play a role in
      the structural organization and function of the Golgi complex.

PMID- 10964697
TI  - Functional analysis of five endothelin-B receptor mutations found in human
      Hirschsprung disease patients.
AB  - Several missense mutations of the endothelin-B receptor (EDNRB) associated with
      Hirschsprung disease have recently been identified. Five mutated EDNRB (A183G,
      W276C, R319W, M374I and P383L) cDNAs were transiently expressed in several cell
      lines to examine the effects of these mutations. Ligand-receptor binding
      experiments demonstrated that all mutants examined here accept endothelins with a
      high affinity. Especially, the affinity of endothelins to P383L was increased.
      However, the number of binding sites of A183G, W276C and P383L was markedly
      decreased. The subcellular localization of these mutant receptors was the same as
      that of wild-type EDNRB, whereas the amount of protein of each mutant receptor
      was decreased. All mutant receptors were impaired in intracellular Ca(2+)
      mobilization. These findings indicate that these missense mutations result in
      loss of function of EDNRB, and may provide the molecular pathological basis of
      Hirschsprung disease in some individuals.

PMID- 10964698
TI  - Isolation of novel mouse genes differentially expressed in brain using cDNA
      microarray.
AB  - The major issue in the post-genome sequencing era is determination of gene
      expression patterns in variety of biological systems. A microarray system is a
      powerful technology for analyzing the expression profile of thousands of genes at
      one experiment. In this study, we identified highly expressed genes in mouse
      brain using the cDNA microarray carrying 2304 cDNAs derived from oligo-capped
      mouse cDNA library. Nine genes were highly expressed in adult mouse brain
      compared to kidney, liver, and skeletal muscle. Tissue distribution analysis by
      reverse transcription-coupled polymerase chain reaction (RT-PCR) revealed that
      consistent with the microarray data, all of the selected 9 genes were
      predominantly expressed in the brain. A database search showed that 5 of the 9
      genes, MBP, SC1, HiAT3, S100 protein-beta, and SNAP25, were previously known to
      be expressed at high level in the brain and in the nervous system. One gene was
      highly sequenced similar to rat S-Rex-s/human NSP-C, suggesting that the gene is
      a mouse homologue. The remaining three genes did not match to known genes in the
      GenBank/EMBL database, indicating that these are novel genes highly expressed in
      the brain. Taken together, our cDNA microarray system can be an excellent tool
      for identifying differentially expressed genes in mouse brain.

PMID- 10964699
TI  - The calcium-sensing receptor stimulates JNK in MDCK cells.
AB  - The calcium-sensing receptor (CaR) stimulates ERK1 in rat fibroblasts, but its
      effect on other MAP kinases is not known. We used a model of renal distal tubule,
      the MDCK cell, to determine the effects of CaR stimulation on Jun kinase (JNK)
      activity. Stimulation of the CaR with 5 mM Ca(2+) resulted in a time-dependent
      increase in JNK activity. Activation of JNK occurred preferentially with
      stimulation on the basal surface relative to the apical surface. Basal
      administration of the CaR agonist gadolinium (30 microm) also stimulated JNK
      activity. Pertussis toxin blocked the ability of both CaR agonists to stimulate
      JNK, indicating that the effect was mediated through G(ialpha) class G proteins.
      Finally, we used confocal microscopy to determine that the CaR was located
      predominantly on the basal surface. These studies demonstrate for the first time
      that the CaR stimulates JNK activity.

PMID- 10964701
TI  - X-ray crystallographic analysis of pokeweed antiviral protein-II after reductive
      methylation of lysine residues.
AB  - Pokeweed antiviral protein II (PAP-II) is a naturally occurring protein isolated
      from early summer leaves of the pokeweed plant (Phytolacca americana). PAP-II
      belongs to a family of ribosome-inactivating proteins which catalytically
      deadenylate ribosomal and viral RNA. The chemical modification of PAP-II by
      reductive methylation of its lysine residues significantly improved the crystal
      quality for X-ray diffraction studies. Hexagonal crystals of the modified PAP-II,
      with unit cell parameters a = b = 92.51 A, c = 79.05 A, were obtained using 1.8 M
      Na/K phosphate as the precipitant. These crystals contained one enzyme molecule
      per asymmetric unit and diffracted up to 2.4 A, when exposed to a synchroton
      source.

PMID- 10964700
TI  - Purification and characterization of extracellular superoxide dismutase in mouse
      lung.
AB  - Extracellular superoxide dismutase (EC-SOD) is the major isozyme of SOD in
      arteries, but is also abundant in lungs. In particular, mouse lungs contain large
      amounts of EC-SOD compared to lungs in other mammals. This suggests that EC-SOD
      may have an amplified function in the mouse lung. This study describes the
      purification and characterization of mouse EC-SOD as well as its localization in
      mouse lung. Mouse EC-SOD exists primarily as a homotetramer composed of a pair of
      dimers linked through disulfide bonds present in the heparin-binding domains of
      each subunit. In addition, mouse EC-SOD can exist in active multimeric forms. We
      developed and utilized a polyclonal antibody to mouse EC-SOD to immunolocalize EC
      SOD in mouse lung. EC-SOD labeling is strongest in the matrix of vessels,
      airways, and alveolar septa. This localization suggests that EC-SOD may have
      important functions in pulmonary biology, perhaps in the modulation of nitric
      oxide-dependent responses.

PMID- 10964702
TI  - Affinity maturation of natural antibody using a chain shuffling technique and the
      expression of recombinant antibodies in Escherichia coli.
AB  - The affinity of natural antibody (Ka = 8 x 10(6) M(-1)) recognizing preS1 of
      hepatitis B virus (HBV) was improved by replacing the heavy (H) chain gene with
      repertoires of VH genes, obtained from two nonimmunized donors. Two separate
      clones, 1C2 and 1E4, showed affinities of 2.3 x 10(7) and 5.2 x 10(7) M(-1),
      which were increased by factors of 2.8 and 6.5, respectively, compared to the
      parental clone. Recombinant scFvs (rscFvs) were expressed as fusion protein with
      minor coat protein, pIII, and secreted into medium after 3 h of induction with 1
      mM IPTG. The expression level of functional rscFv capable of binding to preS1
      reached a peak after 6-10 h (1C2) and 8-10 h (1E4) of IPTG induction, and
      afterwards decreased gradually. In order to achieve the overexpression of rscFv
      in E. coli, gene encoding scFv of 1C2 or 1E4 was inserted into pRSET vector.
      RscFvs were overexpressed as cytoplasmic inclusion bodies in E. coli BL 21
      strain, which were denatured and carefully refolded using a continuous dialysis
      system. The purified recombinant fragments were pure when analyzed by SDS-PAGE
      and had the predicted size of 34 kDa. Clone 1E4 used the heavy chain gene
      belonging to family VII and subgroup III. Chain shuffling offers an alternative
      to random point mutation for affinity maturation of human antibody in vitro.

PMID- 10964703
TI  - Diversity of voltage-gated sodium channels in the ascidian larval nervous system.
AB  - To gain insight into the origin of the molecular diversity of voltage-gated
      sodium channels (NaVs), a putative sodium channel gene (TuNa2) was cloned from
      the protochordate ascidian. TuNa2 showed two unusual features in its primary
      structure; (1) lysine in the P-region of the third repeat, a critical site
      determining ion selectivity, was changed to glutamic acid, predicting that the
      ionic permeability would not be rigidly sodium-selective (2) the III-IV linker,
      determinant of fast inactivation, was only weakly conserved. In contrast with a
      pan-neuronally expressed NaV (TuNa1), expression of TuNa2 was confined to subsets
      of neurons including motor neurons, suggesting that TuNa2 plays specialized roles
      in electrical activities unique to these neurons. Basic FGF, a neural inducer in
      the ascidian embryo, induces TuNa2 RNA expression in the ectodermal cells at
      lower doses than that required for TuNa1 gene expression. Thus, two types of NaV
      may play distinct roles and their gene expressions are controlled by distinct
      mechanisms.

PMID- 10964704
TI  - Identification of a juxtamembrane segment of the glutamate receptor delta2
      subunit required for the plasma membrane localization.
AB  - Glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in
      cerebellar Purkinje cells and is specifically targeted to parallel fiber
      synapses, where GluRdelta2 plays important roles in synaptic plasticity, motor
      learning and synapse formation. Here, we investigated the mechanism of GluRdelta2
      sorting using MDCK epithelial cells. Immunocytochemical analysis of subcellular
      localization showed that GluRdelta2 expressed in MDCK cells was predominantly
      distributed in the plasma membrane. By examining the subcellular localization of
      GluRdelta2 mutants with various deletions in the carboxyl-terminal cytoplasmic
      region, we identified J segment adjacent to transmembrane segment M4 as a key
      region for the efficient targeting of GluRdelta2 to the plasma membrane. On the
      other hand, the carboxyl terminus of GluRdelta2 essential for interaction with
      PDZ domain proteins was dispensable for the plasma membrane localization. Our
      results suggest that the juxtamembrane segment and the PDZ domain target site at
      the carboxyl terminus of GluRdelta2 play differential roles in plasma membrane
      targeting, synapse localization and signal transduction.

PMID- 10964705
TI  - Crystal structures of the ribonuclease MC1 from bitter gourd seeds, complexed
      with 2'-UMP or 3'-UMP, reveal structural basis for uridine specificity.
AB  - Ribonuclease MC1 (RNase MC1) isolated from seeds of bitter gourd (Momordica
      charantia) consists of 190 amino acids and is characterized by a preferential
      cleavage at the 5'-side of uridine. This uridine specificity distinguishes RNase
      MC1 from other enzymes belonging to the RNase T2 family. The three-dimensional
      structures of RNase MC1, in a complex with either 2'-UMP or 3'-UMP, were
      determined at 1.48 and 1.77 A resolutions, respectively. The side chains of Gln9
      and Asn71 interact with O4 and N3, respectively, of the uracil base by hydrogen
      bondings. In addition, the uracil base is sandwiched by the hydrophobic side
      chains of Leu73 and Phe80. Compared with these amino acid residues and
      corresponding residues in RNases in the RNase T2 family, Gln9 and Phe80 are
      highly conserved in the RNases in T2 family, while Asn71 and Leu73 in RNase MC1
      are variant in sequences. It is thus likely that interactions of the side chains
      of Asn71 and Leu73 with the uracil base are responsible for the absolute uridine
      specificity of RNase MC1. Site-directed mutagenesis experiments showed that
      replacement of Asn by Thr decreased both the catalytic efficiency and the binding
      affinity by 2.3- and 7.0-fold, respectively, and substitution of Leu73 for Ala
      predominantly decreased the binding affinity by 14. 5-fold, compared with
      findings in case of wild-type RNase MC1. It is thus demonstrated that Asn71 and
      Leu73 play an essential role in uridine preference for RNase MC1.

PMID- 10964706
TI  - Novel kinetics of mammalian glutathione synthetase: characterization of gamma
      glutamyl substrate cooperative binding.
AB  - Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP
      forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. Mammalian
      glutathione synthetase is a homodimer with each subunit containing an active
      site. We report the detailed kinetic data for purified recombinant rat
      glutathione synthetase. It has the highest specific activity (11 micromol/min/mg)
      reported for any mammalian glutathione synthetase. The apparent K(m) values for
      ATP and glycine are 37 and 913 microM, respectively. The Lineweaver-Burk double
      reciprocal plot for gamma-glutamyl substrate binding revealed a departure from
      linearity indicating cooperative binding. Quantitative analysis of the kinetic
      results for gamma-glutamyl substrate binding gives a Hill coefficient (h) of 0.
      576, which shows the negative cooperativity. Neither ATP, the other substrate
      involved in forming the enzyme-bound gamma-glutamyl phosphate intermediate, nor
      glycine, which attacks this intermediate to form GSH, exhibit any cooperativity.
      The cooperative binding of gamma-glutamyl substrate is not affected by ATP
      concentration. Thus, mammalian glutathione synthetase is an allosteric enzyme.

PMID- 10964707
TI  - Novel proteinaceous toxins from the box jellyfish (sea wasp) Carybdea rastoni.
AB  - During summer and autumn, the box jellyfish (sea wasp) Carybdea rastoni is one of
      the most bothersome stinging pests to swimmers and bathers on the Japanese coast.
      Two labile but potent hemolytic toxins from the tentacles of Carybdea rastoni
      were isolated in their active forms using newly developed purification methods.
      The molecular masses of the isolated C. rastoni toxin-A and toxin-B (CrTX-A and
      CrTX-B) are 43 and 46 kDa, respectively, as calculated from SDS-PAGE. In the
      present study, we sequenced the full-length cDNA (1600 bp), which encodes both
      CrTX-A and CrTX-B. The deduced 450 amino acid sequence of the CrTXs, showed no
      significant homology with any known protein. This report presents the first
      complete sequence of a proteinaceous jellyfish toxin. Furthermore, it was
      revealed that CrTX-A was primarily localized in the nematocyst, whereas CrTX-B
      was detected only in the tentacle. Because the nematocyst is the organ
      responsible for the cnidarian sting, the remainder of the study focused on the
      toxicity of CrTX-A. We found that CrTX-A was fatally toxic to mice at 20
      microg/kg (i.v.) and crayfish at 5 microg/kg (i.p.). Subcutaneously injected CrTX
      A (0.1 microg) caused inflammation of mouse skin. These results showed that CrTX
      A is responsible for the cutaneous inflammation observed in humans stung by C.
      rastoni.

PMID- 10964708
TI  - Isolation and characterization of a novel protein toxin from the Hawaiian box
      jellyfish (sea wasp) Carybdea alata.
AB  - The box jellyfish (sea wasp) Carybdea alata Reynaud, 1830 (Cubozoa) is
      distributed widely in the tropics. The sting of C. alata causes severe pain and
      cutaneous inflammation in humans. We successfully isolated C. alata toxin-A (CaTX
      A, 43 kDa) and -B (CaTX-B, 45 kDa) for the first time from the tentacle of C.
      alata collected at a site along the Hawaiian shore. The experimental results
      showed that CaTX-A, but not CaTX-B, is present in the nematocyst, the organ
      responsible for stinging. Both CaTX-A and -B showed potent hemolytic activity,
      with CaTX-A being lethally toxic to crayfish when administered via
      intraperitoneal injection. Furthermore, we sequenced the cDNA encoding CaTX-A.
      The deduced amino acid sequence of CaTX-A (463 amino acids) showed 43.7% homology
      to Carybdea rastoni toxins (CrTXs) but not with any other known proteins.
      Therefore, these jellyfish toxins potentially represent a novel class of
      bioactive proteins. Secondary structure analysis of CaTX-A and CrTXs suggested
      the presence of amphiphilic alpha-helices, which are also seen in several known
      hemolytic or cytolytic protein toxins, including peptide toxins.

PMID- 10964709
TI  - A novel 31-amino-acid-length endothelin, ET-1(1-31), can act as a biologically
      active peptide for vascular smooth muscle cells.
AB  - Human chymase produces a novel endothelin-1 with 31 amino-acid length ?ET-1(1
      31)?, which is longer than conventional ET-1, ?ET-1(1-21)?. The aim of our study
      was to investigate the role of ET-1(1-31) on porcine coronary vascular smooth
      muscle cell (VSMC). Although the increase in [Ca(2+)](i) by ET-1(1-31) was 10
      times weaker than that of ET-1(1-21), ET-1(1-31) showed equivalent potency in
      VSMC proliferation, c-fos/c-myc mRNA expression and cell cycle analysis with ET
      1(1-21). ET-1(1-31) significantly induced expression of cyclin D1 but not those
      of cyclin D2 or D3. These effects were specifically inhibited by BQ485, an ET(A)
      receptor antagonist, although that of ET-1(1-21) was not specific to BQ485,
      suggesting different receptor specificity from ET-1(1-21). These results indicate
      that ET-1(1-31) also can involve a VSMC proliferation process such as
      atherosclerosis, although it has weaker vasoconstricting potency and different
      receptor subtypes on VSMC from those of ET-1(1-21).

PMID- 10964710
TI  - Arabidopsis chloroplast chaperonin 10 is a calmodulin-binding protein.
AB  - Calcium regulates diverse cellular activities in plants through the action of
      calmodulin (CaM). By using (35)S-labeled CaM to screen an Arabidopsis seedling
      cDNA expression library, a cDNA designated as AtCh-CPN10 (Arabidopsis thaliana
      chloroplast chaperonin 10) was cloned. Chloroplast CPN10, a nuclear-encoded
      protein, is a functional homolog of E. coli GroES. It is believed that CPN60 and
      CPN10 are involved in the assembly of Rubisco, a key enzyme involved in the
      photosynthetic pathway. Northern analysis revealed that AtCh-CPN10 is highly
      expressed in green tissues. The recombinant AtCh-CPN10 binds to CaM in a calcium
      dependent manner. Deletion mutants revealed that there is only one CaM-binding
      site in the last 31 amino acids of the AtCh-CPN10 at the C-terminal end. The CaM
      binding region in AtCh-CPN10 has higher homology to other chloroplast CPN10s in
      comparison to GroES and mitochondrial CPN10s, suggesting that CaM may only bind
      to chloroplast CPN10s. Furthermore, the results also suggest that the calcium/CaM
      messenger system is involved in regulating Rubisco assembly in the chloroplast,
      thereby influencing photosynthesis.

PMID- 10964711
TI  - A distinct FMRP polysomal population at an advanced stage of mammalian
      erythropoiesis.
AB  - The fragile-X syndrome is a mental disorder caused by the absence of FMRP (the
      Fragile-X Mental Retardation Protein). While FMRP is found to be associated with
      the ribosomal components, its precise translational function remains to be
      defined. Here we report that FMRP is not found with the abundant free polysomes
      of the reticulocyte lysate, but rather with a heavy ribonucleoprotein complex
      sedimenting over 400S. This unusual distribution of FMRP at an advanced stage of
      mammalian erythropoiesis may unveil the discrete role of FMRP in translation.

PMID- 10964712
TI  - Muscle aldolase decreases muscle FBPase sensitivity toward AMP inhibition.
AB  - Muscle aldolase bound to muscle FBPase (K(d) = 8.7 microM) decreases the latter's
      sensitivity towards AMP inhibition. I(0.5) of muscle FBPase was increased from
      0.06 microM to 0.65 microM when determined in the presence of 10 microM of muscle
      aldolase. In the presence of 10 microM of liver aldolase I(0.5) of liver FBPase
      was increased only twofold, from 11.0 microM to 21.7 microM. The effect of muscle
      aldolase on liver FBPase and liver aldolase on muscle FBPase is rather
      negligible. Aldolase slightly affected interaction of FBPase with magnesium ions
      decreasing K(a) and Hill constant (n). No effect of aldolase on FBPase pH optimum
      was observed.

PMID- 10964713
TI  - Promoter variants of the human mannose-binding lectin gene show different
      binding.
AB  - Mannose-binding lectin (MBL) levels in the plasma of humans are highly variable.
      The level is influenced by gene mutations in exon1 and the promoter. Here we
      describe the distribution of three point mutations linked with a deletion in the
      MBL gene promoter in populations of Central Africa, Thailand, and Papua New
      Guinea. Among African children we find 20% with the wild-type allele, 53% are
      heterozygous, and 27% are homozygous for the mutation. In Thailand we find 65%
      with the wild-type allele, 33% are heterozygous, and 2% are homozygous for the
      variant. In Papua New Guinea the polymorphism is not found. The occurrence of the
      mutation was associated with MBL levels in the plasma (P = 0.043).
      Oligonucleotides derived from the variant promoter regions bind proteins
      differently according to their DNA sequence. The binding of proteins can be
      influenced by induction with interleukin-6.

PMID- 10964714
TI  - Genomic structure and in vivo expression of the human organic anion transporter 1
      (hOAT1) gene.
AB  - The human organic anion transporter 1 (hOAT1) plays a key role in the secretion
      of an array of potentially toxic organic anions including many clinically
      important drugs. Here we report on the genomic cloning of hOAT1. A human genomic
      library was used for screening of a PAC (P1 artificial chromosome) clone applying
      PCR techniques. Sequencing of several restriction subclones and of a PCR
      generated clone revealed that the hOAT1 gene spans 8.2 kb and is composed of 10
      exons divided by 9 introns. RT-PCR studies in a human kidney specimen led to the
      detection of two new splice variants, hOAT1-3 and hOAT1-4, showing a 132-bp in
      frame deletion. Using fluorescence in situ hybridization (FISH) we mapped the
      hOAT1 gene as a single signal to chromosome 11q13.1-q13.2. Additionally, 600 bp
      of the 5' flanking region was analyzed, illustrating the probable transcription
      start site at nt -280, a NF-kappaB-site at nt -397 and several putative
      transcription factor binding sites.

PMID- 10964715
TI  - Design of a novel small peptide targeted against a tumor-specific receptor.
AB  - EGFRvIII is the most common deletion variant of the epidermal growth factor
      receptor and is found in cancers of the brain, breast, ovary, and lung. The
      complete absence of the receptor in healthy tissues makes it an ideal tumor
      marker. We sought to design a peptide ligand against EGFRvIII for development as
      a diagnostic imaging agent. We used the concept of hydropathic complementarity to
      search for sequences whose amino acid sidechains display a reciprocal pattern of
      hydropathicity to those of the deletion junction of EGFRvIII. The resulting
      peptide (PEPHC1) was synthesized and tested for binding to EGFRvIII and EGFR. In
      in vitro assays, PEPHC1 bound the recombinant EGFRvIII extracellular domain or
      full-length EGFRvIII solubilized from cell membranes in preference to native
      EGFR. These results demonstrate the utility of hydropathic complementarity as a
      basis for the design of highly specific ligands that may prove useful as tumor
      targeting agents.

PMID- 10964716
TI  - Altered ion channel activity in murine colonic smooth muscle myocytes in an
      experimental colitis model.
AB  - We have investigated the activity of calcium and potassium channels in a murine
      model of experimental colitis. Colonic myocytes from dextran sulphate sodium
      (DSS)-treated mice were examined by whole cell patch clamp techniques.
      Myeloperoxidase activity was enhanced 3. 5-fold in DSS-treated mouse colon. In
      whole cell voltage clamp, depolarization predominantly evoked net transient
      outward currents in DSS-treated mice and inward Ca(2+) currents in control
      myocytes. Voltage-dependent L-type Ca(2+) currents were studied using
      intracellular Cs(+) in the patch pipette. Inward Ca(2+) currents were markedly
      suppressed in inflamed colon. The peak currents at +10 mV depolarization were 
      3.93 +/- 0.88 pA/pF in control (n = 12) and -1.14 +/- 0.19 (n = 10) in DSS mice.
      In contrast there was no change in the amplitude, kinetics, or steady-state
      inactivation properties of the transient outward currents in control or DSS
      treated colonic myocytes. Inflammation significantly enhanced activation of the
      ATP-sensitive K(+) channel. At a holding potential of -50 mV, the K(ATP) channel
      opener lemakalim induced an inward current of 2.02 +/- 0.5 pA/pF in control (n =
      20) and 4.19 +/- 1.17 pA/pF in DSS-treated colon. These currents were abolished
      by glibenclamide. The present results suggest that inflammation of the colon
      results in selective changes in ion channel activity of smooth muscle cells.

PMID- 10964717
TI  - Genomic structure and alternative splicing of chicken angiopoietin-2.
AB  - Angiopoietin-1 (Ang-1) prevents endothelial cell apoptosis and promotes blood
      vessel stability, while angiopoietin-2 (Ang-2), a natural antagonist of Ang-1,
      disrupts blood vessel structure and induces apoptosis. We have sequenced the
      chicken angiopoietin-2 gene that spans about 46 kb of DNA and is split in 9 exons
      by 8 introns. Alternative splicing of the gene gives rise to three different
      species of Ang-2 mRNAs: Ang-2A, Ang-2B, and Ang-2C. The three mRNA isoforms, also
      present in humans, codify for proteins with an identical fibrinogen-like C
      terminal domain and a different coiled-coil N-terminal domain. Ang-2A and
      particularly Ang-2C are expressed in immature testis and regressed adult testis
      undergoing vascular remodeling, while their expression is barely detectable in
      quiescent adult testis. Conversely, Ang-2B is only detectable in adult testis.
      The new isoforms with truncated amino-terminal domains may modulate the Tie2
      receptor during vascular angiogenesis and regression.

PMID- 10964718
TI  - Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new
      Notch target genes.
AB  - Hey genes (Hey1, Hey2 and HeyL) encode a new group of basic helix-loop-helix
      transcription factors that are related to the hairy/Enhancer of split genes. In
      the present study, we cloned and characterized the promoter region of the human
      and mouse Hey1 gene. The transcription initiation site was located 138
      nucleotides upstream of the start codon. There is a minimal sequence element (nt 
      30 to -247) that is essential and important for basal transcription in three
      different cell types. Further upstream, a highly conserved sequence block (nt 
      324 to -646; approximately 90% human/mouse similarity) could be identified that
      contains several putative binding sites for transcription factors and likely
      represents an important regulatory region for this gene. Cotransfection
      experiments demonstrated that the mHey1 promoter activity is up-regulated by the
      activated form of all four mammalian Notch receptors via two functional RBP
      Jkappa binding sites. The other members of the Hey gene family, Hey2 and HeyL,
      also possess RBP-Jkappa binding sites and they are similarly responsive to Notch
      signaling. Thus, our data clearly demonstrate that Hey genes form a new class of
      Notch signal transducers that should prove to be relevant in various
      developmental processes.

PMID- 10964720
TI  - High-affinity Ca(2+) binding inhibits autoactivation of rat trypsinogen.
AB  - The recent discovery that mutation Asn21 --> Ile in the human cationic
      trypsinogen (Tg) is associated with hereditary pancreatitis has brought into
      focus the functional role of amino acid 21 in mammalian Tgs. In the present
      paper, the effect of mutations Thr21 --> Asn and Thr21 --> Ile on the Ca(2+)
      dependence of zymogen activation was investigated, using the autolysis-resistant
      rat Tg mutant Arg117 --> His. In the absence of Ca(2+), rat Tg exhibited low but
      significant basal autoactivation, which was inhibited by micromolar
      concentrations of Ca(2+) (IC(50) 2.6 microM). Interestingly, basal autoactivation
      was diminished in both mutants, and no further inhibition by micromolar Ca(2+)
      was detectable. Millimolar Ca(2+) concentrations markedly and comparably
      stimulated autoactivation of wild-type and mutant zymogens (EC(50) 1.7-2.4 mM).
      The results indicate that rat Tg is subject to dual regulation by Ca(2+),
      allowing zymogen stabilization in a low-Ca(2+) environment and efficient
      activation in a high-Ca(2+) milieu.

PMID- 10964719
TI  - A novel avian hypothalamic peptide inhibiting gonadotropin release.
AB  - The neuropeptide control of gonadotropin secretion at the level of the anterior
      pituitary gland is primarily through the stimulatory action of the hypothalamic
      decapeptide, gonadotropin-releasing hormone (GnRH), which was originally isolated
      from mammals and subsequently from non-mammals. To date, however, an inhibitory
      peptide of gonadotropin release is unknown in vertebrates. Here we show, in a
      bird, that the hypothalamus also contains a novel peptide which inhibits
      gonadotropin release. Acetic acid extracts of quail brains were passed through C
      18 reversed-phase cartridges, and then the retained material was subjected to the
      reversed-phase and cation-exchange high-performance liquid chromatography (HPLC).
      The peptide was isolated from avian brain and shown to have the sequence Ser-Ile
      Lys-Pro-Ser-Ala-Tyr-Leu-Pro-Leu-Arg-Phe-NH(2). Cell bodies and terminals
      containing this peptide were localized immunohistochemically in the
      paraventricular nucleus and median eminence, respectively. This peptide
      inhibited, in a dose-related way, gonadotropin release from cultured quail
      anterior pituitaries. This is the first hypothalamic peptide inhibiting
      gonadotropin release reported in a vertebrate. We therefore term it gonadotropin
      inhibitory hormone (GnIH).

PMID- 10964721
TI  - Spin trapping of vascular nitric oxide using colloid Fe(II)
      diethyldithiocarbamate.
AB  - Currently available EPR spin-trapping techniques are not sensitive enough for
      quantification of basal vascular nitric oxide (NO) production from isolated
      vessels. Here we demonstrate that this goal can be achieved by the use of colloid
      Fe(DETC)(2). Rabbit aortic or venous strips incubated with 250 microM colloid
      Fe(DETC)(2) exhibited a linear increase in tissue-associated NO-Fe(DETC)(2) EPR
      signal during 1 h. Removal of endothelium or addition of 3 mM N(G)-nitro-l
      arginine methyl ester (L-NAME) inhibited the signal. The basal NO production was
      estimated as 5.9 +/- 0.5 and 8.3 +/- 2.1 pmol/min/cm(2) in thoracic aorta and
      vena cava, respectively. Adding sodium nitrite (10 microM) or xanthine/xanthine
      oxidase in the incubation medium did not modify the intensity of the basal NO
      Fe(DETC)(2) EPR signal. Reducing agents were not required with this method and
      superoxide dismutase activity was unchanged by the Fe(DETC)(2) complex. We
      conclude that colloid Fe(DETC)(2) may be a useful tool for direct detection of
      low amounts of NO in vascular tissue.

PMID- 10964722
TI  - Oxidized proteins in Alzheimer's plasma.
AB  - The levels of oxidatively modified proteins were examined in blood from
      Alzheimer's disease (AD) patients, non-AD controls, and AD relatives. Oxidative
      modification was measured by reacting the protein carbonyls with 2,4
      dinitrophenyl hydrazine (DNPH). The total oxidized proteins were determined by
      HPLC, while specific protein oxidation was assessed from Western blots of
      electrophoretic gels using antibody to the DNP derivatives. Statistically
      significant elevations (P < 0.05) of total oxidized proteins were observed in
      both AD subjects and AD relatives when compared with non-AD controls. Moreover, a
      protein band (e.g., MW = 78-kDa) was uniquely oxidized in the plasma of AD
      subjects. Furthermore, this protein from AD subjects was more susceptible to in
      vitro oxidation. These data suggest that such oxidized proteins may be useful as
      biomarkers for the detection and evaluation of AD.

PMID- 10964724
TI  - Eicosanoid 12(S)-HETE activates phosphatidylinositol 3-kinase.
AB  - The arachidonic acid metabolite of 12 lipoxygenase, 12(S)-hydroxyeicosatetraenoic
      acid (12(S)-HETE) promotes metastatic behavior of tumor cells. In this study we
      set out to identify 12(S)-HETE signaling pathways, and their contribution to
      cellular functions in A431 epidermoid carcinoma. (1) 12(S)-HETE stimulated
      phosphotyrosine associated PI3 kinase activity. (2) 12(S)-HETE stimulated ERK1/2
      in a PI3 kinase dependent manner. (3) PI3 kinase affected the 12(S)-HETE
      stimulated Raf/MEK/ERK cascade at the level of MEK. (4) 12(S)-HETE stimulated
      ERK1/2 via PKCzeta. (5) 12(S)-HETE stimulated cell migration on laminin, which
      was eliminated by PI3 kinase and cPKC inhibitors, but it was unaffected by
      inhibition of ERK1/2.

PMID- 10964723
TI  - Cloning and characterization of human estrogen receptor beta promoter.
AB  - Estrogen receptors beta (ERbeta) belong to the nuclear receptor superfamily of
      ligand-dependent transcription factors that play critical roles in regulating
      genes involved in a wide array of biological processes. To investigate regulation
      of tissue-specific expression of ERbeta, we cloned and characterized a 2.1
      kilobase 5'-flanking region of the human ERbeta gene. Two major transcription
      start sites were identified by primer extension and rapid amplification of 5'
      cDNA end. The human ERbeta proximal promoter contains both TATA box and initiator
      element (Inr) and is GC-rich with a GC content of 65%. An Alu repeat sequence
      containing an ER-dependent transcription enhancer exists between -1416 and -1703.
      The full-length 5'-flanking sequence of ERbeta fused to a luciferase reporter
      exhibited functional promoter activity in ERbeta-positive TSUPr1 cell, but not in
      ERbeta-negative DU145 cells. In addition, DNase I protection assays of the
      proximal promoter showed unique protection patterns with nuclear extracts from
      TSUPr1 cells and ERbeta negative HeLa cells, suggesting presence of cell-specific
      trans-acting factors that mediate tissue/cell-specific ERbeta expression. Serial
      deletion analysis revealed that a 293-bp region encompassing the TATA box and Inr
      element possesses basal promoter activity.

PMID- 10964725
TI  - Involvement of cyclooxygenase 2 in the protective effect of 17beta-estradiol on
      hypercholesterolemic rabbit aorta.
AB  - The involvement of cyclooxygenase (COX) in the effects of 17beta-estradiol was
      investigated on hypercholesterolemic rabbits aorta. Acetylsalycilic acid,
      nimesulide, or SQ22536 was used as respective antagonist of COX-1, COX-2, or
      adenylate cyclase using aortic rings precontracted with phenylephrine and exposed
      to cumulative concentrations of acetylcholine (ACh). The relaxation effect of ACh
      was impaired by hypercholesterolemia and restored by an 8-week 17beta-estradiol
      treatment. In the control group treated with estrogen, nimesulide,
      acetylsalycilic acid, or SQ22536 slightly reduced the response to ACh. In
      hypercholesterolemic rabbits treated with estrogen, nimesulide significantly
      reduced the maximal relaxation and shifted to the right the relaxation curve of
      ACh, whereas acetylsalycilic acid did not modify the maximal response to ACh but
      displaced slightly the concentration-response curve. SQ22536 reduced the relaxant
      effect of ACh down to the level obtained in the presence of nimesulide. These
      results suggest that the protective effect of 17beta-estradiol against
      hypercholesterolemia involved COX-2/adenylate cyclase pathway.

PMID- 10964726
TI  - Mutation of the nucleophilic elbow of the Lux-specific thioesterase from Vibrio
      harveyi.
AB  - Myristoyl-ACP thioesterase (LuxD) from Vibrio harveyi causes the slow release of
      fatty acids for reduction into the aldehyde substrate required for the bacterial
      bioluminescence reaction. The active site Ser nucleophile (S(114)) of the LuxD
      thioesterase is in a gamma-turn with a sequence (AXS(114)XS) quite different from
      the standard motif of GXSXG found in almost all (thio) esterases and lipases. The
      presence of an Arg residue (R(118)) in the first turn of the helix after the
      gamma-turn also distinguishes LuxD from other enzymes. Mutation of R(118) to Leu
      inactivated the enzyme and prevented acylation of the Ser(114) nucleophile, while
      even a conservative replacement with Lys resulted in over 75% loss of the same
      functions, suggesting that R(118) helps maintain the configuration of the active
      site. In contrast, replacement of S(116) with Gly but not Ala stimulated the
      esterase and deacylation rates by over threefold. Purification of the S116G
      mutant to homogeneity and analyses of its intrinsic fluorescence on acylation
      with myristoyl-CoA clearly demonstrated that this mutant was much more active
      than wild-type LuxD. The presence of S(116) rather than the expected Gly residue
      in the gamma-turn containing the Ser nucleophile may function so that release of
      fatty acids from LuxD is restricted allowing a more efficient delivery of fatty
      acids to the luminescent system.

PMID- 10964727
TI  - Expression of melanin-concentrating hormone receptors in insulin-producing cells:
      MCH stimulates insulin release in RINm5F and CRI-G1 cell-lines.
AB  - Melanin-concentrating hormone (MCH) is a hypothalamic orexigenic peptide.
      Recently, an orphan G-protein-coupled receptor (SLC-1) was identified that binds
      MCH with high affinity. Here, we demonstrate the mRNA expression of this receptor
      in insulin-producing cells including CRI-G1 and RINm5F cells, and in rat islets
      of Langerhans. Immunofluorescence studies in CRI-G1 and RINm5F cell-lines
      demonstrated cell-surface expression of the receptor. Rat MCH significantly
      stimulated insulin secretion in both cell-lines. The potency and the efficacy of
      MCH were significantly increased in the simultaneous presence of forskolin,
      suggesting that MCH may amplify the insulinotropic effect of cyclic AMP elevating
      stimuli. Salmon MCH, which differs from rat/human MCH by six amino acids, was
      less efficacious than rat/human MCH in stimulating insulin release. The data
      provide evidence for the expression of MCH receptors in insulin producing cells.
      The insulinotropic effect of MCH may contribute to the regulation of metabolism
      and energy balance by this peptide.

PMID- 10964728
TI  - The imaging of lumbar spinal stenosis.
AB  - Lumbar spinal stenosis (LSS) is a relatively common condition of varied aetiology
      which results in chronic compression of the cauda equina. It becomes clinically
      relevant when giving rise to symptoms of neurogenic claudication or leg pain.
      Lumbar spinal stenosis can be classified based on anatomy or aetiology and the
      diagnosis in any single case should include a consideration of both the site and
      the cause. Plain radiography is of limited value. Myelography with erect lateral
      flexion/extension views will demonstrate the dynamic component of the stenosis
      which cannot be appreciated on plain computed tomography (CT) or magnetic
      resonance imaging (MRI). Therefore, in patients with a good history of
      symptomatic LSS, and a borderline stenosis on MRI, CT myelography is recommended
      as the definitive pre-operative imaging investigation.

PMID- 10964729
TI  - Pictorial review. Ultrasound of the testis.
AB  - Ultrasound examination is the primary imaging investigation used in initial
      evaluation of the symptomatic testis. In this review the ultrasound appearances
      of a range of testicular lesions are demonstrated. Particular attention is given
      to the subject of testicular microlithiasis and its link with germ-cell
      neoplasia, and also to the sonographic features of epidermoid cysts that may
      allow testis-sparing surgery.

PMID- 10964731
TI  - Who should be performing routine abdominal ultrasound? A prospective double-blind
      study comparing the accuracy of radiologist and radiographer.
AB  - AIM: To compare the accuracy of radiographers and radiologists in routine
      abdominal ultrasound. MATERIALS AND METHODS: One hundred consecutive patients
      attending for routine abdominal ultrasound were included. Each patient was
      examined by both a radiographer and radiologist. Both operators noted their
      findings and wrote a concluding report without conferring. Reports were compared.
      Where there was disagreement the patient was either re-examined by another
      radiologist or had further investigation. RESULTS: Of 100 patients, 52 were men
      and 48 were women. The age range was 19-88 years (median 52 years). Thirty-seven
      patients had renal tract ultrasound, one had an aortic ultrasound and 62 had
      general upper abdominal ultrasound. In 44 cases both operators reported the
      examination as normal. In 49 cases both operators reported the examinations as
      abnormal and there was complete agreement between the operators. In seven cases
      there was not complete agreement between operators. Three of these disagreements
      were considered minor and four major. In three of the seven cases the
      radiographer was correct, and in four the radiologist was correct. CONCLUSION:
      Experienced radiographers and radiologists are highly accurate in performing and
      interpreting routine abdominal sonography. Both operators missed a small minority
      of abnormalities. There was no statistically significant difference in the
      accuracy of radiographers and radiologist.

PMID- 10964730
TI  - Relationships between radiologists and clinicians: results from three surveys.
AB  - AIM: To analyse reasons for and the nature of clinico-radiological contacts and
      their clinical impact. MATERIALS AND METHODS: Three different surveys were
      performed. (1) Data concerning contacts between staff radiologists (n = 20) and
      clinicians during 10 consecutive working days were collected; (2) staff
      clinicians (n = 174) filled in a questionnaire asking for their opinions about
      relationships with radiologists; (3) staff radiologists collected data about
      contacts with clinicians related to more urgent/complicated cases. Radiologists
      assessed the clinical impact of the radiological procedure and of the
      consultation. RESULTS: (1) During 220 working days 20 radiologists had a mean of
      3.95 contacts per day (48.2% personal contacts, 51.8% telephone contacts),
      amounting to a personal total of 21.65 min per day. These contacts amounted to a
      total of 7.08 h per day, roughly one whole-time equivalent radiologist. (2) These
      consultations helped to refine the diagnostic strategy often (12.6%) or sometimes
      (71.4%) and to alter therapeutic decisions often (10.4%) or sometimes (56.6%).
      (3) The initial clinical diagnosis was changed in 50% of cases and the therapy
      was substantially changed on the basis of further radiological investigations and
      clinical-radiological discussion in 60% of cases. CONCLUSION: Clinical
      radiological consultations are time consuming but have a beneficial diagnostic
      and therapeutic impact.

PMID- 10964732
TI  - Desferrioxamine-induced long bone changes in thalassaemic patients - radiographic
      features, prevalence and relations with growth.
AB  - AIM: To study the radiographic findings of desferrioxamine-induced bone
      dysplasia, its prevalence and relation to growth in thalassaemic patients.
      MATERIALS AND METHODS: A cross-sectional study was performed in 35 thalassaemic
      patients on a hypertransfusion scheme and chelation therapy at a dose not
      exceeding 50 mg/kg/day. Radiographs of the left hand taken for bone age
      assessment in consecutive patients over the past 12 months were evaluated for
      signs of desferrioxamine-induced bone dysplasia. The findings were correlated
      with data on growth, chelation and body iron content. RESULTS: Twelve of 35
      patients had evidence of desferrioxamine-induced long bone dysplasia. There was
      no significant difference in the groups with and without radiographic evidence of
      bone dysplasia with respect to the height percentile at time of initiation of
      therapy, height percentile at time of radiography, skeletal age delay, age at
      starting chelation, chelation dose and duration, units of blood transfused,
      average chelation dose, and serum ferritin levels at time of radiography. Both
      groups showed a reduced percentile growth with a significantly greater reduction
      (P = 0.03) in the patients with dysplastic change. CONCLUSION: Desferrioxamine
      induced bone dysplasia is associated with height reduction and can be seen in
      patients receiving desferrioxamine chelation therapy at doses of less than 50
      mg/kg/day. Awareness of the diagnosis is of importance as reduction of the
      desferrioxamine dose may improve bone growth.

PMID- 10964733
TI  - Digital radiography of the skeleton using a large-area detector based on
      amorphous silicon technology: image quality and potential for dose reduction in
      comparison with screen-film radiography.
AB  - AIM: The purpose of this study was to evaluate a large-area, flat-panel X-ray
      detector (FD), based on caesium-iodide (CsI) and amorphous silicon (a-Si) with
      respect to skeletal radiography. Conventional images were compared with digital
      radiographs using identical and reduced radiation doses. MATERIALS AND METHODS:
      Thirty consecutive patients were studied prospectively using conventional screen
      film radiography (SFR; detector dose 2.5 microGy). Digital images were taken from
      the same patients with detector doses of 2.5, 1.25 and 0.625 microGy,
      respectively. The active-matrix detector had a panel size of 43 x 43 cm, a matrix
      of 3 x 3K, and a pixel size of 143 microm. All hard copies were presented in a
      random order to eight independent observers, who rated image quality according to
      subjective quality criteria. Results were assessed for significance using the
      Student's t -test (confidence level 95%). RESULTS: A statistically significant
      preference for digital over conventional images was revealed for all quality
      criteria, except for over-exposure (detector dose 2.5 microGy). Digital images
      with a 50% dose showed a small, statistically not significant, inferiority
      compared with SFR. The FD-technique was significantly inferior to SFR at 75% dose
      reduction regarding bone cortex and trabecula, contrast and overall impression.
      No statistically significant differences were found with regard to over- and
      under-exposure and soft tissue presentation. CONCLUSION: Amorphous silicon-based
      digital radiography yields good image quality. The potential for dose reduction
      depends on the clinical query.

PMID- 10964734
TI  - The value of the absent bow tie sign in MRI of bucket-handle tears.
AB  - AIM: To assess the accuracy of the absent bow tie sign in diagnosing bucket
      handle meniscal tears (BHT) of the knee menisci. MATERIALS AND METHODS: During a
      3-year period, we correlated the MRI and arthroscopic findings and the presence
      of the various signs. One hundred and seven knees were reviewed: 74 where either
      MRI or arthroscopy had identified a BHT and 33 which were either normal (31), or
      a simple tear was identified (2). All cases were reviewed by a single radiologist
      with a musculoskeletal interest blinded to the original results. Each was
      assessed for the presence of (1) a central meniscal fragment, (2) the double
      posterior cruciate ligament (PCL) sign, (3) the bow tie sign and (4) the
      contribution of a 3D-volume sequence. RESULTS: Optimal results were obtained
      using standard sequences and a 3D-volume sequence, giving a sensitivity of 74%
      and positive predictive value of 89%. The bow tie sign gave a sensitivity of 71%
      and positive predictive value of 76%, significantly less than previous reports.
      The 18 BHTs diagnosed by arthroscopy but missed by MRI showed other abnormal
      findings at MRI and were not reported as normal. CONCLUSION: We were not able to
      reproduce the previously reported high sensitivity and specificity of the absent
      bow tie sign. Despite optimization of all factors, the accurate diagnosis of a
      bucket handle tear remains difficult, and is most reliably made by identifying a
      central meniscal fragment, rather than relying on secondary signs such as the
      absent bow tie sign.

PMID- 10964735
TI  - Differentiation of lymphadenopathy in different forms of carcinoma with Doppler
      sonography.
AB  - AIM: The aim of the study was to show whether it may be possible to characterize
      malignant nodes of different aetiologies with Doppler imaging. Non-Hodgkin's
      lymphoma (NHL) and nasopharyneal carcinoma (NPC) were used as the models.
      MATERIALS AND METHODS: A prospective study was undertaken using colour Doppler
      sonography in 60 enlarged peripheral lymph nodes of 34 patients with either
      lymphoma or NPC. The vascular distribution, peak systolic velocity (PSV), end
      diastolic velocity (EDV), resistivity index (RI) and the pulsatility index (PI)
      of the largest node on each side of the patient were investigated. RESULTS: The
      vascular distribution was predominantly 'capsular and central' or 'capsular' in
      57 nodes, consistent with previous descriptions, but there was no significant
      difference in the mean PSV (lymphoma: 20.0 cm/s; NPC: 21.86 cm/s;P > 0.05) and
      mean EDV (lymphoma: 5.95 cm/s; NPC: 5.07 cm/s;P > 0.05). However, significant
      differences were shown in the mean RI (lymphoma: 0.71; NPC: 0.81;P < 0.05) and
      mean PI (lymphoma: 1.43; NPC: 1.88;P < 0.05) of these two groups of lymph nodes.
      CONCLUSIONS: There is significant difference in the Doppler waveform between
      malignant nodes affected by lymphoma or NPC, suggesting that further
      differentiation of malignant nodes may be possible.

PMID- 10964736
TI  - Early pulmonary involvement in ankylosing spondylitis: assessment with thin
      section CT.
AB  - AIM: To determine the frequency and the distribution of early pulmonary lesions
      in patients with ankylosing spondylitis (AS) and a normal chest X-ray on thin
      section CT and to correlate the CT findings with the results of pulmonary
      function tests and clinical data. MATERIALS AND METHODS: Twenty-five patients
      with clinically proven AS and no history of smoking underwent clinical
      examinations, pulmonary function tests (PFT), chest radiography, and thin-section
      CT. Four of 25 patients (16%), who had obvious signs on plain films suggestive of
      pre-existing disorders unrelated to AS were excluded. RESULTS: Fifteen of 21
      patients (71%) had abnormalities on thin-section CT. The most frequent
      abnormalities were thickening of the interlobular septa in seven of 21 patients
      (33%), mild bronchial wall thickening in (6/21, 29%), pleural thickening and
      pleuropulmonary irregularities (both 29%) and linear septal thickening (6/21,
      29%). In six patients there were no signs of pleuropulmonary involvement. Eight
      of 15 patients (53%) with abnormal and four of six patients (67%) with normal CT
      findings revealed mild restrictive lung function impairment. CONCLUSION: Patients
      with AS but a normal chest radiograph frequently have abnormalities on thin
      section CT. As these abnormalities are usually subtle and their extent does not
      correlate with functional and clinical data, the overall routine impact of thin
      section CT in the diagnosis of AS is limited.

PMID- 10964737
TI  - Clinical deterioration in ARDS - an unchanged chest radiograph and functioning
      chest drains do not exclude an acute tension pneumothorax.

PMID- 10964738
TI  - Budd-Chiari syndrome: peripheral abnormal intensity of the liver on magnetic
      resonance imaging.

PMID- 10964739
TI  - Testicular microlithiasis in a patient with a mediastinal germ cell tumour.

PMID- 10964740
TI  - Cardiac tamponade: A rare complication of attempted stenting in malignant
      superior vena caval obstruction.

PMID- 10964742
TI  - Kimura's disease of the pharynx.

PMID- 10964741
TI  - Endobronchial mucoepidermoid carcinoma in childhood: case report and literature
      review.

PMID- 10964743
TI  - Reply to dr millward

PMID- 10964744
TI  - Buckling of the tethering catheter causes migration of a temporary caval filter
      to the right atrium.

PMID- 10964746
TI  - Magnetic resonance imaging versus radionuclide scintigraphy for screening in bone
      metastases.

PMID- 10964745
TI  - Magnetic resonance imaging versus radionuclide scintigraphy for screening in bone
      metastases.

PMID- 10964747
TI  - Reply to drs evans and robertson

PMID- 10964748
TI  - The generation of localized calcium rises mediated by cell adhesion molecules and
      their role in neuronal growth cone motility.
AB  - Neurite growth and guidance depends on the transduction of extracellular guidance
      cues into motile responses by the sensory apparatus at the tip of the neurite,
      the growth cone. Contact of the growth cone with extracellular ligands leads to
      the cytoskeletal reorganisation required for changes in rate of motility and
      direction of outgrowth. Differential adhesion mediated by cell adhesion molecules
      and signal transduction pathways mediated by growth cone receptors were once seen
      as separate but cooperative events in controlling growth cone motility. However,
      recent findings suggest that cell adhesion molecules can activate novel
      signalling pathways in the growth cone by the recruitment of fibroblast growth
      factor receptors leading to neurite outgrowth. This Review focuses on work by
      various laboratories centering on the intracellular consequences of the cell
      adhesion molecule-mediated activation of the fibroblast growth factor receptor.
      These include activation of a lipase cascade including phospholipase C and
      diacylglycerol lipase and culminating in the release of arachidonic acid. This
      release of arachidonic acid is proposed to activate the transient opening of
      voltage dependent ion-channels leading to localised rises in growth Ca(2+).
      Recent findings demonstrating this previously undetectable rise in Ca(2+) in the
      growth cone are discussed in light of the proposed roles and mechanisms of Ca(2+)
      in controlling neurite outgrowth. The Ca(2+) rises are thought to induce the
      activation of GAP43 and Ca(2+)/calmodulin-dependent kinase II, molecules
      implicated in the modulation of cytoskeletal remodelling. The evidence that this
      pathway may be involved in the guidance of retinal ganglion cells is evaluated.

PMID- 10964749
TI  - Acylphosphatase is a strong apoptosis inducer in HeLa cell line.
AB  - Acylphosphatase (AcP) is a low-molecular-weight protein widely distributed in
      many vertebrate tissues with a yet unknown physiologic function. To study the in
      vivo behavior of AcP, HeLa cells were transiently transfected with a vector
      expressing the AcP/EGFP fusion protein. Analysis of the transfected cells showed
      a high level of cellular death in cells expressing the AcP/EGFP fusion protein
      with respect to control cells expressing EGFP alone. Flow cytometry and time
      lapse analysis of AcP/EGFP transfected cells evidenced a typical pattern of
      apoptosis. Surprisingly, cells transfected with a mutated form of AcP, with
      negligible in vitro acylphosphatase activity, undergo apoptosis as well as cells
      transfected with wild-type protein, suggesting that the physiologic role of AcP
      could be not related to this catalytic activity.

PMID- 10964750
TI  - Overexpression of Cdx1 and Cdx2 homeogenes enhances expression of the HLA-I in HT
      29 cells.
AB  - We have previously reported that down-regulation of Cdx1 and Cdx2 mRNA expression
      is associated with colon carcinogenesis, and that coordinated reexpression of
      these genes in the HT29 colon cancer-derived cell line leads to a reduced
      malignant phenotype. Here we show that restoring Cdx1 and Cdx2 expression in HT29
      cells enhanced the antigen presentation system, as reflected by a strong
      induction of the concentration of HLA-I molecules at the cell surface, resulting
      from increased expression of the HLA-I mRNA. Expression of the LMP2 proteasomal
      protein was also strongly induced by Cdx1 and Cdx2 at the transcriptional level,
      whereas TAP1 expression which is under the control of the same bidirectional
      promoter as LMP2 remained unchanged. Furthermore, expression of the adhesion
      molecule ICAM-1, which works in concert with HLA-I, and of the cell death
      promoter Fas was also increased upon Cdx1 and Cdx2 expression. Taken together,
      these results suggest that loss of Cdx1 and Cdx2 expression during colorectal
      carcinogenesis could favor the escape of tumor cells from the immune system. In
      conclusion, restoration of Cdx1 and Cdx2 expression should be considered in
      immunotherapeutic strategies for colorectal cancer.

PMID- 10964751
TI  - Angiostatin induces mitotic cell death of proliferating endothelial cells.
AB  - Angiostatin is an inhibitor of tumor angiogenesis that induces regression of
      experimental tumors and enhances the antitumor effects of radiation therapy. We
      report that the cytotoxic effects of angiostatin are restricted to the
      proliferating endothelial cell population. In addition, angiostatin and ionizing
      radiation (IR) interact by inducing death of dividing endothelial cells. We also
      show that angiostatin and IR interact to inhibit endothelial cell migration.
      These findings demonstrate that angiostatin targets the proliferating tumor
      vasculature and provide a mechanistic basis for the cytotoxic interaction of
      angiostatin and IR.

PMID- 10964752
TI  - Multiple, closely spaced alternative 5' exons in the DmCKIIbeta gene of
      Drosophila melanogaster.
AB  - Drosophila melanogaster casein kinase II (CKII) is composed of catalytic alpha
      and regulatory beta subunits. Using the two-hybrid system, we have isolated a
      number of cDNAs that are related to a previously published cDNA encoding the beta
      subunit, but exhibit divergent 5' sequences. To determine the source of this
      sequence variation, we have isolated the gene encoding the beta subunit of CKII.
      The beta gene contains five exons encompassing the complete open reading frame,
      as well as five alternative exons in the 5' untranslated region (UTR). Only one
      5' UTR exon is contained in each cDNA, implying five distinct classes of
      transcript. In addition, the beta gene contains at least two poly(A) addition
      signals which generate additional complexity at the 3' end. The complex pattern
      of transcription may serve a role in the spatial and/or temporal expression of
      the beta subunit since, with one exception, all transcripts encode the full
      length beta polypeptide. Phylogenetic comparison of the beta genes of Drosophila,
      C. elegans, and mammals reveals three invariant introns as well as evidence of
      recent intron gain/loss.

PMID- 10964753
TI  - Deletion mutagenesis of the 5' psbA2 region in Synechocystis 6803: identification
      of a putative cis element involved in photoregulation.
AB  - Three Synechocystis 6803 mutants, with deletions in the upstream region of the
      light-regulated psbA2 gene, were constructed. All three mutants grew
      photoautotrophically but they were affected in psbA2 expression. In one of the
      mutants, DeltaU80, psbA2 transcription levels were not suppressed under low light
      conditions and production of psbA2 transcripts occurred also in darkness, in
      contrast to the situation in the control strain. Comparative sequence analyses of
      the mutants identified a hexanucleotide repeat as possible cis element in psbA2
      light regulation. Electrophoresis mobility shift assays showed that protein
      binding to the hexanucleotide repeat decreased with light intensity, consistent
      with a hypothesis that the repeat harbors a binding site for a repressor protein.
      Repeats similar to that in psbA2 were found also in the upstream region of other
      light-regulated genes in Synechocystsis 6803. We refer to these hexanucleotide
      repeats as High Light Regulatory 1 (HLR1) sequences.

PMID- 10964754
TI  - STAT5-Dependent CyclinD1 and Bcl-xL expression in Bcr-Abl-transformed cells.
AB  - Signal transducers and activators of transcription (STATs) are a family of
      transcription factors that were originally identified as mediators of cytokine
      induced gene expression. We and others have recently shown that STAT5 also plays
      a major role in cellular transformation by the Bcr-Abl oncogene. Here we show
      that the antiapoptotic bcl-xL gene product and the cell cycle regulator cyclin D1
      are targets of STAT5 in Bcr-Abl-transformed cells. In the CML cell line K562 and
      in BaF3 cells ectopically expressing Bcr-Abl, both the cyclin D1 and bcl-x
      promoters are highly active. The activity of these promoters can be strongly
      repressed by cotransfection of a dominant negative (DN) mutant of STAT5.
      Moreover, the cyclin D1 and bcl-x promoters contain STAT binding sites to which
      STAT5 constitutively binds in Bcr-Abl transformed cells. These results suggest
      that STAT5 contributes to transformation by Bcr-Abl by induction of cyclin D1 and
      bcl-xL expression.

PMID- 10964755
TI  - EGTA treatment causes the synthesis of heat shock proteins in sea urchin embryos.
AB  - Paracentrotus lividus embryos, at post-blastular stage, when subjected to a rise
      in temperature from physiologic (20 degrees C) to 31 degrees C, synthesize a
      large group of heat shock proteins (hsps), and show a severe inhibition of bulk
      protein synthesis. We show, by mono- and two-dimensional electrophoresis, that
      also EGTA (ethylene glycol-bis[beta-aminoethyl ether] tetraacetic acid) treatment
      induces in sea urchin embryos both marked inhibition of bulk protein synthesis
      and the synthesis of the entire set of hsps. Furthermore, EGTA-treated sea urchin
      embryos are able to survive at a temperature otherwise lethal (35 degrees C)
      becoming thermotolerant. Because incubation with a different calcium-chelator,
      EDTA (ethylenediaminetetraacetic acid), or in calcium-free medium did not induce
      hsps synthesis we conclude that the stress response caused by EGTA is not related
      to its calcium chelator function.

PMID- 10964756
TI  - Telomere dynamics in cells with introduced telomerase: a rapid assay for
      telomerase activity on telomeres.
AB  - Most immortal cell lines derived from human cancers or transformed in vitro
      maintain telomeres by endogenous expression of telomerase. In the present work,
      immortal cells that already express endogenous telomerase activity were induced
      to overexpress an exogenous telomerase (hTERT) and were analyzed for changes in
      telomere length. Introduction of hTERT into telomerase-positive immortal cell
      lines results in elevated telomerase activity as measured by the TRAP assay,
      leading to elongated telomeres in the cell lines tested. We explore possibilities
      for regulatory differences among the cell lines, including the level of
      overexpression of the catalytic subunit hTERT and the endogenous levels of
      telomere binding proteins. Reducing levels of hTERT expression with a construct
      containing an inefficient translation initiation sequence provided sufficient
      telomerase expression for maximal rates of telomere elongation. Overexpression of
      the hTERT alters the telomere length normally maintained in these cells and
      provides a very useful assay for the rapid analysis of telomerase activity on its
      native substrate, telomeres.

PMID- 10964757
TI  - Housekeeping genes commanded to commit suicide in CpG-cleavage commitment
      upstream of Bcl-2 inhibition in caspase-dependent and -independent pathways.
AB  - A CpG-specific commitment common to both caspase-dependent and -independent cell
      deaths implies critical gene activity from epigenetic modulation. Using a focused
      microarray (genechip) of 22 housekeeping genes, which have canonical CpG islands
      at 5'-promoter regions, here we show critical regulation of vital intermediary
      metabolism and cell structure that are common to both caspase-dependent fasL
      mediated and caspase-independent etoposide-mediated cell deaths. Gene activity of
      at least twofold under or over control levels and common to both cell death
      pathways was considered to be significantly regulated in common. Seven genes
      controlling energy production in glycolysis, tricarboxylic acid cycle, and the
      respiratory electron transport chain were significantly downregulated in common.
      Energy depletion is lethal. Downregulated pyruvate dehydrogenase E1 gene, in
      addition, suggested primary metabolic acidification. Cell acidification is also
      lethal. Critical derangement of the cell structure was suggested by common
      downregulation of the basal histone gene H2A.X which is required for nucleosome
      assembly. Common upregulation of the alpha-tubulin gene suggested perturbation of
      vital microtubular dynamics. Gene-commanded cell suicide was suggested. We
      further show that a Bcl-2 overexpression of three- to fourfold above normal
      levels could not prevent the CpG-specific megabase DNA cleavages in the two cell
      death pathways, but abolished their low-molecular-weight 200-bp ladder cleavages.
      Together with incomplete suppression of the other apoptotic expressions, the Bcl
      2 inhibition point appeared downstream from the CpG-cleavage commitment point.

PMID- 10964758
TI  - Rate of neurotoxicant exposure determines morphologic manifestations of distal
      axonopathy.
AB  - Exposure to a variety of agricultural, industrial, and pharmaceutical chemicals
      produces nerve damage classified as a central-peripheral distal axonopathy.
      Morphologically, this axonopathy is characterized by distal axon swellings and
      secondary degeneration. Over the past 25 years substantial research efforts have
      been devoted toward deciphering the molecular mechanisms of these presumed
      hallmark neuropathic features. However, recent studies suggest that axon swelling
      and degeneration are related to subchronic low-dose neurotoxicant exposure rates
      (i.e., mg toxicant/kg/day) and not to the development of neurophysiological
      deficits or behavioral toxicity. This suggests these phenomena are nonspecific
      and of uncertain pathophysiologic relevance. This possibility has significant
      implications for research investigating mechanisms of neurotoxicity, development
      of exposure biomarkers, design of risk assessment models, neurotoxicant
      classification schemes, and clinical diagnosis and treatment of toxic
      neuropathies. In this commentary we will review the evidence for the dose-related
      dependency of distal axonopathies and discuss how this concept might influence
      our current understanding of chemical-induced neurotoxicities.

PMID- 10964759
TI  - Effects of in utero exposure to linuron on androgen-dependent reproductive
      development in the male Crl:CD(SD)BR rat.
AB  - Linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) is a herbicide that
      blocks androgen action in the male rat. Studies were undertaken to characterize
      the ability of linuron to activate transcription through the human androgen
      receptor (AR) in vitro and to determine whether in utero linuron exposure induces
      dose-responsive alterations in androgen-dependent reproductive development in the
      male rat. In vitro, linuron competitively antagonized transcriptional activity of
      the AR induced by dihydrotestosterone (DHT) in a dose-responsive manner with an
      equilibrium dissociation constant (K(B)) of 75.8 x 10(-8) M. Pregnant rats were
      administered linuron by gavage at 0, 12.5, 25, or 50 mg/kg/day (n = 11/group)
      from gestation day 12 to 21. Anogenital distance of resulting offspring was
      unaffected, whereas male areola/nipple retention was increased in a dose
      responsive manner. Hypoplastic testes in adult offspring were seen in 2/56 rats
      (2/10 litters), 8/69 rats (4/11 litters), and 5/44 rats (3/8 litters), while
      hypoplastic epididymides occurred in 1/56 rats (1/10 litters), 8/69 rats (4/11
      litters), and 2/44 rats (1/8 litters) in the 12.5, 25, and 50 mg/kg/day dose
      groups, respectively. Partial agenesis of the epididymides was observed in 3/44
      rats (2/8 litters) only in the 50 mg/kg/day group. These data indicate that in
      utero exposure to linuron preferentially impairs testosterone-mediated, rather
      than DHT-mediated, reproductive development. This effect is distinctly different
      from the effects induced by flutamide, an AR antagonist that shares structural
      similarities with linuron. Furthermore, these data suggest that dose-response
      studies utilizing late gestational exposure to endocrine-active compounds may be
      more robust than the traditional or EPA-modified multigeneration protocols in
      identifying adverse effects.

PMID- 10964760
TI  - Alteration of programmed cell death and gene expression by 5-bromodeoxyuridine
      during limb development in mice.
AB  - Some chemicals are known to induce limb malformations in mice. The occurrence of
      limb abnormality induced by chemical reagents is due to changes in the programmed
      cell death (PCD). 5-Bromodeoxyuridine (BrdU) is known as a potent teratogen and
      has been reported to induce polydactyly and other limb malformations in rodents
      (DiPaolo, Science 145, 501-503, 1964). Here, we undertook the morphological and
      genetic analyses of fetuses with limb malformations in BrdU-treated mice, in
      order to investigate an alteration of gene expression that resembles that of
      mutant mice with similar limb malformations. The fetuses of the BrdU-treated mice
      exhibited preaxial polydactyly and preaxial triphalangism of the hindlimb at a
      high incidence. Our observations showed that the PCD in the preaxial necrotic
      zone was found to be delayed or absent on day 11 of pregnancy. Histological
      analyses of these fetuses showed that the preaxial apical ectodermal ridge (AER)
      of the hindlimb was hyperplastic and consisted of several irregular layers. In
      observation of the whole-mount in situ hybridization, we detected the anterior
      extended overexpression of Hoxd-11 and Hoxd-13 genes in the mesenchyme cells and
      the overexpression of Fgf4 and Fgf8 genes in the anterior region of the AER of
      hindlimbs of BrdU-treated fetuses. Our study shows that the injection of BrdU
      changed the PCD and gene expression during limb development and induced time
      specific limb malformations during fetal development. This examination of the
      changes of the PCD and gene expression will be useful markers for the
      investigation of toxicities and teratologieties of other chemicals now present in
      the world environment.

PMID- 10964762
TI  - Activation of respiratory burst in human granulocytes by polychlorinated
      biphenyls: A structure-activity study.
AB  - The respiratory burst in human granulocytes activated by 33 different congeners
      of polychlorinated biphenyls (PCBs) was measured as luminol-amplified
      chemoluminescence. The selection of 20 (training set) compounds was based on
      multivariate chemical characterization, laying the groundwork for covering the
      whole chemical series of tetra- through hepta-chlorinated PCBs. In addition 6
      congeners were used as a validation set, and 7 were mono- to tri-chlorinated
      congeners representing low-chlorinated compounds not covered by the training set.
      Only ortho-substituted biphenyls activate respiratory burst. There is a
      correlation between activated respiratory burst and the total surface area of
      congeners up to 230 x 10(-20) m(2). Congeners of larger size show a reduced
      activity. There is also a correlation between respiratory burst activity and the
      number of ortho-substituents. Furthermore, there is also a correlation with
      parameters that describe absolute hardness of the molecule and respiratory burst
      activity. Congeners with a 2,4, 6-substitution on one biphenyl ring are optimal
      activators. In conclusion, all three factors, size, rotation, and electronic
      properties, which are not independent of each other, are important for the
      activity of the PCBs.

PMID- 10964761
TI  - Persistent depletion of I kappa B alpha and interleukin-8 expression in human
      pulmonary epithelial cells exposed to quartz particles.
AB  - Chronic inflammation and fibrosis following quartz inhalation has been associated
      with persistent up-regulation of several "pro-inflammatory" genes, which are
      commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF
      kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo
      synthesis is considered to comprise a negative feedback loop in transient
      inflammation. To investigate this mechanism in particle inflammation, we have
      studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2),
      in relation to the expression of IL-8. Although both quartz and TiO(2) were found
      to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha
      depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term
      increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early
      enhancement of IL-8 expression and release was similar for both particles. Up
      regulation of IL-8 expression was found to persist with quartz only. Cotreatment
      with PDTC and curcumin reduced particle-elicited IL-8 response, whereas
      cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and
      TiO(2)-treated cells. Our results demonstrate that mineral dusts cause
      IkappaBalpha degradation, a transient increase in de novo synthesis of
      IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells.
      While IkappaBalpha degradation and early IL-8 expression seem to be general
      particle phenomena, particle-specific characteristics impact on activation of
      IkappaBalpha gene transcription, apparently accounting for the different
      proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term.
      These observations may provide an explanation for the transient versus the
      persistent pulmonary inflammatory status and subsequent differences in pathogenic
      potency of TiO(2) and quartz.

PMID- 10964763
TI  - Protective effects of phenyl-N-tert-butylnitrone on the potentiation of noise
      induced hearing loss by carbon monoxide.
AB  - Free radical injury has been implicated in cochlear damage resulting from
      exposure to high-intensity noise and due to carbon monoxide (CO) hypoxia.
      Although exposure to noise plus CO is common in occupational settings and noise
      induced hearing loss (NIHL) is enhanced in the presence of CO, potential
      mechanisms resulting in auditory impairment have not been studied. This study
      evaluates protective effects of the free radical scavenger phenyl-N-tert
      butylnitrone (PBN) against potentiation of NIHL by CO. Three PBN administration
      protocols have been evaluated in subjects exposed to noise plus CO or noise
      alone. Long Evans hooded rats were exposed to octave band noise at 100 dB(Lin),
      center frequency (cf) = 13.6 kHz for a duration of 2 h. The level of CO used was
      1200 ppm. Endpoints used to detect permanent auditory impairment were compound
      action potential (CAP) threshold and 1 microV root mean square (RMS) cochlear
      microphonic (CM). Testing was done 4 weeks following exposure. PBN administration
      prior to and following simultaneous exposure provided significant protection
      against auditory impairment in subjects receiving noise plus CO. Partial
      protection was observed in the protocols where PBN was injected following noise
      plus CO exposure. PBN administration appeared to reduce auditory impairment in
      animals exposed to noise alone, but the difference was not found to be
      statistically significant. Protective effects of PBN following simultaneous
      exposure to noise plus CO suggest that free radicals may be generated during
      combined exposure.

PMID- 10964764
TI  - Studies of ochratoxin A-induced inhibition of phenylalanine hydroxylase and its
      reversal by phenylalanine.
AB  - Ochratoxin A (OTA) is a nephrotoxic, hepatotoxic, and teratogenic mycotoxin
      produced by storage molds on a variety of foodstuffs. Its chemical structure is
      composed of an isocumarin part linked to l-phenylalanine. Inhibition of
      phenylalanine hydroxylase and other enzymes that use phenylalanine as substrate
      is based on this structural homology. We have examined the effects of low doses
      of ochratoxin A on the activity of phenylalanine hydroxylase in kidney and in
      liver of experimental animals. Daily administration of ochratoxin A (50 microg/kg
      body wt, for 10 and 35 days, respectively) caused a significant reduction in the
      phenylalanine hydroxylase activity. Inhibition was more pronounced in liver than
      in kidney, although actual ochratoxin A concentration was higher in the kidney
      tissue. We observed an apparent increase in the affinity of phenylalanine
      hydroxylase for substrate following OTA administration to animals. However,
      simple competitive inhibition was observed for both tissues in vitro (K(i liver)
      = 0.0119 +/- 0.002 mM and K(i kidney) = 0.13 +/- 0.026 mM). Simultaneous
      application of ochratoxin A with phenylalanine could reduce inhibition of
      phenylalanine hydroxylase, in particular in liver. Enzyme activity was almost
      completely preserved after 35 days of combined treatment. The results obtained
      suggest that daily administration of ochratoxin A in low doses produced an
      inhibitory effect that could be diminished by competitive action of l
      phenylalanine.

PMID- 10964765
TI  - Insoluble components of concentrated air particles mediate alveolar macrophage
      responses in vitro.
AB  - We sought to characterize the bioactive constituents of concentrated ambient air
      particles (CAPs) through correlation of alveolar macrophage (AM) biological
      responses (production of TNF, macrophage inflammatory protein (MIP-2), nitrite;
      cell viability) to components of particle samples. CAPs samples collected on
      different days showed a range of bioactivity and a strong correlation was found
      between AM cytokine release and increased AM light scatter, a flow cytometric
      measure of relative particle load. Evaluation of soluble and insoluble fractions
      of CAPs suspensions indicate that 1) most biological effects on AMs are mediated
      by insoluble components and certain particle adsorbed factors such as endotoxin;
      2) the variable bioactivity of CAPs collected on different days arises primarily
      from differences in the relative proportion of insoluble and soluble mass present
      in particle suspensions; and 3) the activation state of the AM influences which
      insoluble components are most bioactive. Use of endotoxin neutralizing agents
      (e.g., polymyxin-B) showed particle-adsorbed endotoxin in CAPs suspensions causes
      activation of normal (control) AMs while other (nonendotoxin) components are
      predominantly responsible for the enhanced cytokine release observed by primed
      AMs incubated with CAPs. The AM biological response did not correlate with any of
      a panel of elements quantified within insoluble CAPs samples (Al, Cd, Cr, Cu, Fe,
      Mg, Mn, Ni, S, Ti, V). These data demonstrate an important role for cell
      activation and phagocytosis of insoluble particulate matter in the response of
      AMs to CAPs suspensions.

PMID- 10964766
TI  - Cephaloridine-induced inhibition of cytochrome c oxidase activity in the
      mitochondria of cultured renal epithelial cells (LLC-PK(1)) as a possible
      mechanism of its nephrotoxicity.
AB  - To clarify the mechanism of cephalosporin nephrotoxicity, the effects of
      cephaloridine (CLD), a nephrotoxic cephalosporin antibiotic, on the mitochondria
      of the pig kidney proximal tubular epithelial cell line LLC-PK(1) were studied in
      culture. The activity of cytochrome c oxidase in the mitochondria of LLC-PK(1)
      cells was significantly decreased from 9 h after addition of 1.0 mM CLD to the
      cultured cells. These effects were dose-dependent and accompanied with a
      significant decrease in the ATP content in the cells, followed by marked
      morphological changes in the mitochondria. These alterations were observed in the
      treated cells before the increase in lipid peroxidation. The activities of NADH
      cytochrome c reductase and succinate dehydrogenase in the mitochondria and NADPH
      cytochrome P450 reductase, NADH-cytochrome b(5) reductase, and 7-ethoxycoumarin O
      deethylase in the microsomes of the treated cells were not affected. Superoxide
      anion production by the mitochondria prepared from LLC-PK(1) cells or NADH
      cytochrome c reductase was not affected by addition of CLD (1-10 mM), but
      adriamycin (0.1 mM) or paraquat (0.1 mM) significantly increased the superoxide
      anion production. These results suggested that the primary action of CLD is
      inhibition of cytochrome c oxidase activity in the mitochondrial electron
      transport chain, which decreases intracellular ATP content in renal tubular
      epithelial cells and that these effects of CLD are followed by increased lipid
      peroxidation and cellular injury.

PMID- 10964767
TI  - The 1918 influenza virus: A killer comes into view.

PMID- 10964768
TI  - The p20 gene product of Citrus tristeza virus accumulates in the amorphous
      inclusion bodies.
AB  - Citrus tristeza virus (CTV) has 10 3' open reading frames (ORFs) of unknown
      function except for the two coat proteins. The highest produced subgenomic RNAs
      are those of the major coat protein gene (p25) and the 3' most genes, p20 and
      p23. The proteins from three ORFs, p25, p27, and p20, were examined in the yeast
      two-hybrid assay for the interactions between themselves and to one another. The
      p20 protein exhibited a high affinity for itself, suggesting that it might
      aggregate in infected cells. The cytopathology of CTV infections includes
      characteristic paracrystalline and amorphous inclusions in the phloem elements of
      infected citrus. Polyclonal antiserum raised against the bacterial expressed p20
      gene product detected a protein of approximately 22-23 kDa, which accumulated to
      relatively high levels in CTV-infected citrus, but not in healthy citrus.
      Immunogold localization using antibodies to p20 protein showed strong and
      specific labeling of the amorphous inclusion bodies present in CTV-infected
      cells. Mesophyll protoplasts of Nicotiana benthamiana transfected with a CTV
      mutant containing the green fluorescent protein (GFP) ORF fused in-frame to the
      3' end of p20 protein ORF expressed high levels of GFP. The fusion protein was
      concentrated in one specific area in the cytoplasm and lacked an organized shape.
      Accumulation of high levels of p20 protein in infected tissue, specific
      localization of the p20-GFP fusion protein, immunolocalization of p20 protein
      into amorphous inclusions, and strong homologous p20 protein-p20 protein
      interactions in the yeast-two-hybrid assay suggest that the p20 protein of CTV is
      a major component of the amorphous inclusion bodies present in CTV-infected
      cells.

PMID- 10964770
TI  - Analysis of the HIV-1 LTR NF-kappaB-proximal Sp site III: evidence for cell type
      specific gene regulation and viral replication.
AB  - It has been widely demonstrated that the human immunodeficiency virus type 1 (HIV
      1) envelope, specifically the V3 loop of the gp120 spike, evolves to facilitate
      adaptation to different cellular populations within an infected host. Less energy
      has been directed at determining whether the viral promoter, designated the long
      terminal repeat (LTR), also exhibits this adaptive quality. Because of the unique
      nature of the cell populations infected during the course of HIV-1 infection, one
      might expect the opportunity for such adaptation to exist. This would permit
      select viral species to take advantage of the different array of conditions and
      factors influencing transcription within a given cell type. To investigate this
      hypothesis, the function of natural variants of the NF-kappaB-proximal Sp element
      (Sp site III) was examined in human cell line models of the two major cell types
      infected during the natural course of HIV-1 infection, T cells and monocytes.
      Utilizing the HIV-1 LAI molecular clone, which naturally contains a high-affinity
      Sp site III, substitution of low-affinity Sp sites in place of the natural site
      III element markedly decreased viral replication in Jurkat T cells. However,
      these substitutions had relatively small effects on viral replication in U-937
      monocytic cells. Transient transfections of HIV-1 LAI-based LTR-luciferase
      constructs into these cell lines suggest that the large reduction in viral
      replication in Jurkat T cells, caused by low-affinity Sp site III variants, may
      result from reduced basal as well as Vpr- and Tat-activated LTR activities in
      Jurkat T cells compared to those in U-937 monocytic cells. When the function of
      Sp site III was examined in the context of HIV-1 YU-2-based LTR-luciferase
      constructs, substitution of a high-affinity element in place of the natural low
      affinity element resulted in increased basal YU-2 LTR activity in Jurkat T cells
      and reduced activity in U-937 monocytic cells. These observations suggest that
      recruitment of Sp family members to Sp site III is of greater importance to the
      function of the viral promoter in the Jurkat T cell line as compared to the U-937
      monocytic cell line. These observations also suggest that other regions of the
      LTR may compensate for Sp recruitment defects in specific cell populations.

PMID- 10964769
TI  - Whole body positron emission tomography imaging of activated lymphoid tissues
      during acute simian-human immunodeficiency virus 89.6PD infection in rhesus
      macaques.
AB  - Mechanisms of acute retroviral pathogenesis have been examined during primary
      infection of rhesus macaques with simian-human immunodeficiency virus 89.6PD
      (SHIV(89.6PD)). During acute infection, between initial exposure and
      establishment of antigen-specific immune responses that stabilize the virus
      burden, rapid immune system changes influence the viral set-point and dictate
      subsequent steps in disease progression. In a previous study, we described
      specific patterns of lymphocyte activation during acute SHIV(89.6PD) infection.
      We now extend these studies to describe lymphoid tissue activation, using whole
      body positron emission tomography (PET) and the radioactive tracer 2
      [(18)F]fluorodeoxyglucose (FDG). Within a few days after primary infection by
      intravenous, intrarectal, or intravaginal routes, PET-FDG imaging revealed a
      distinct pattern of lymphoid tissue activation centered on axillary, cervical,
      and mediastinum lymph nodes. Increased tissue FDG uptake preceded fulminant virus
      replication at these sites, suggesting that a diffusible factor of host or viral
      origin was responsible for lymphoid tissue changes. These data show that
      activation of lymphoid tissues in the upper body is an early response to virus
      infection and that diffusible mediators of activation might be important targets
      for vaccine or therapeutic intervention strategies.

PMID- 10964771
TI  - Down-regulation of Bgp1(a) viral receptor by interferon-gamma is related to the
      antiviral state and resistance to mouse hepatitis virus 3 infection.
AB  - Together with the evidence that the reduced virus growth and the antiviral state
      induced by interferon (IFN)-gamma, occurring only in macrophages from resistant
      animals, correlated with the decrease of MHV3 binding to macrophage membrane
      proteins, we show here the expression of cellular and viral genes in resistant
      (A/J) and susceptible (BALB/c) mouse macrophages after IFN-gamma
      activation/infection. The expression of interferon response gene 47 and
      interferon regulatory factor 1 genes takes place after IFN-gamma activation in
      both macrophages, indicating their activation. The expression of the biliary
      glycoprotein 1(a) (Bgp1(a), the main virus receptor) decreased only in IFN-gamma
      activated A/J mouse macrophages, in contrast to the expression of the Bgp2
      (alternative receptor), which was not influenced by IFN-gamma activation. The
      synthesis of both viral mRNA and virus particles was delayed only in IFN-gamma
      activated A/J mouse macrophages compared with susceptible BALB/c macrophages.
      Besides the evidence that IFN-gamma may modulate the expression of the Bgp1(a)
      isoform of carcinoembryonic antigen family, these data show that IFN-gamma, which
      induces resistance against MHV3 infection, may be involved in the down-regulation
      of the main viral receptor expression, a key step forward in our understanding of
      the molecular basis of resistance against virus infection.

PMID- 10964772
TI  - Identification of a novel RNA splicing pattern as a basis of restricted cell
      tropism of erythrovirus B19.
AB  - Prior studies on the transcription of erythrovirus B19 have identified a short
      leader sequence associated with all spliced viral transcripts. While some
      variability has been observed in the acceptor for this first intron, studies to
      date in both permissive and nonpermissive cell types have reported a unique
      splice donor site. In the semipermissive MB-02 cell line, we have found that
      splicing of this first intron proceeds almost exclusively via a cryptic CT donor
      downstream of the previously reported GT donor at nucleotide 406. The resulting
      messages for the viral structural proteins and 11-kDa protein are thereby made
      bicistronic, with the first expressible polypeptide being a 34 amino acid fusion
      of the NS-1 and 7.5-kDa proteins. The presence of an upstream open-reading frame
      on these messages is likely to block effective translation of the downstream
      structural protein products. We propose this as a significant mechanism in
      determining B19's tropism on the basis of host cell splicing machinery, and
      present evidence in support of this model. Additionally, this is the first report
      of usage of a noncanonical splice donor in B19, and to our knowledge the first
      report of a CT-AG splice in any system.

PMID- 10964773
TI  - Determinants in the envelope E protein and viral RNA helicase NS3 that influence
      the induction of apoptosis in response to infection with dengue type 1 virus.
AB  - One mechanism by which dengue (DEN) virus may cause cell death is apoptosis. In
      this study, we investigated whether the genetic determinants responsible for
      acquisition by DEN type 1 (DEN-1) virus of mouse neurovirulence interfere with
      the induction of apoptosis. Neurovirulent variant FGA/NA d1d was generated during
      the adaptation of the human isolate of DEN-1 virus strain FGA/89 to grow in
      newborn mouse brains and mosquito cells in vitro [Despres, P. Frenkiel, M. -P.
      Ceccaldi, P.-E. Duarte Dos Santos, C. and Deubel, V. (1998) J. Virol., 72: 823
      829]. Genetic determinants possibly responsible for mouse neurovirulence were
      studied by sequencing the entire genomes of both DEN-1 viruses. Three amino acid
      differences in the envelope E protein and one in the nonstructural NS3 protein
      were found. The cytotoxicity of the mouse-neurovirulent DEN-1 variant was studied
      in different target cells in vitro and compared with the parental strain. FGA/NA
      d1d was more pathogenic for mouse neuroblastoma cells and attenuated for human
      hepatoma cells. Changes in virus replicative functions and virus assembly may
      account, in a large part, for the differences in the induction of apoptosis. Our
      data suggest that identified amino acid substitutions in the envelope E protein
      and viral RNA helicase NS3 may influence DEN-1 virus pathogenicity by altering
      viral growth.

PMID- 10964775
TI  - Involvement of a membrane-associated serine/threonine kinase complex in cellular
      binding of visna virus.
AB  - Previous studies from our laboratory identified cellular membrane proteins that
      mediate binding of visna virus to susceptible cells. In the pilot report,
      antiserum raised to one of these proteins, approximately 45 kDa, was shown to
      both label the surface of susceptible cells and block the binding of visna virus
      to cell membranes. In a recent study, we reported that the same antiserum,
      designated 2-23, significantly inhibited infection by visna virus and
      specifically immunoprecipitated a membrane-associated protein complex from
      susceptible cells, comprised of a approximately 45- kDa protein, as well as a 30
      kDa protein. Because the 30-kDa protein was readily detectable in TRANS[(35)S]
      LABELed susceptible cells, we were able to characterize this protein
      biochemically, as a chondroitin sulfate proteoglycan. In the present study, we
      sought to characterize the approximately 45-kDa protein and examined 2-23 immune
      complexes for the presence of kinase activity. Our data indicate that although in
      vitro kinase assays of 2-23 immunoprecipitates specifically result in the
      phosphorylation of the approximately 45-kDa protein as well as a novel
      approximately 56-kDa protein, only the approximately 45-kDa protein exhibits
      inherent serine/threonine kinase activity. In addition, the kinase activity can
      be isolated in 2-23 immunoprecipitates of membranes prepared from visna virus
      susceptible cells. Finally, in an effort to evaluate the biological relevance of
      our in vitro observations, we examined 2-23 immunoprecipitates of
      [(32)P]orthophosphate-labeled visna-susceptible cells and report that the
      approximately 56-kDa protein is phosphorylated constitutively on serine in vivo.
      Collectively, these data implicate a serine/threonine kinase complex in the
      binding/infection of visna virus.

PMID- 10964774
TI  - Molecular and serologic characterization of novel serotype G8 human rotavirus
      strains detected in Blantyre, Malawi.
AB  - During a 2-year study of diarrhea among children in Blantyre, Malawi, greater
      than 50% of rotavirus strains genotyped by using reverse transcription-polymerase
      chain reaction possessed previously unrecognized combinations of the
      neutralization proteins VP7 and VP4. Serotype G8 rotaviruses, which have been
      identified recently in several African countries, were found to possess P[4] or
      P[6] VP4 genotype specificity. Two of these short electropherotype rotaviruses
      were further investigated: these comprised a P[6], G8 representative strain
      (MW23) and a P[4], G8 representative strain (MW333). The VP7 gene sequences of
      both strains exhibited greatest homology to human and animal serotype G8
      rotaviruses. Sequence analysis of the VP4 gene of MW23 indicated closest identity
      to the P2A[6], G9 strain US1205 from the United States. The VP4 gene of MW333 was
      most closely related to the P[4], G12 strain L26 isolated in the Philippines and
      the Australian P[4], G2 strain RV-5. The NSP4 gene sequences of both strains were
      classified in NSP4 genetic group I. RNA-RNA hybridization demonstrated that each
      of these two strains is related to the DS-1 genogroup of human rotaviruses.
      Subgroup analysis and virus neutralization confirmed complete antigenic
      characterization of MW23 as subgroup I, P2A[6], G8 and MW333 as subgroup I,
      P1B[4], G8. The similarity of the VP7 gene sequences of the prototype strains
      described in this report to bovine serotype G8 rotaviruses suggests that they may
      represent human/bovine reassortant viruses.

PMID- 10964776
TI  - Expression of mutated poliovirus receptors in human neuroblastoma cells
      persistently infected with poliovirus.
AB  - Poliovirus (PV) is able to establish persistent infections in human neuroblastoma
      IMR-32 cells [Colbere-Garapin et al. (1989) Proc. Natl. Acad. Sci. USA 86, 7590].
      During persistent infection, PV mutants are selected that display substitutions
      of residues in regions of the capsid known to interact with the PV receptor
      (PVR), a glycoprotein of the immunoglobulin superfamily. The mechanism of
      persistent infection in IMR-32 cells may therefore involve the selection of
      mutant PVRs. To test this hypothesis, the sequences of the PVR mRNAs in
      uninfected IMR-32 cells and in two independent IMR-32 cell cultures persistently
      infected with the Mahoney strain of PV type 1 (PV1/Mahoney) were determined. The
      PVR mRNA population of uninfected cells was homogeneous, and no mutation was
      repeatedly found, whereas that of persistently infected cells displayed missense
      mutations. Particular mutations were repeatedly detected, and all of them mapped
      to the N-terminal domain of PVR (domain 1), which interacts directly with PV.
      These mutations generated several types of PVR variants with the following
      substitutions: Ala67-->Thr alone, Ala67-->Thr associated with Gly39-->Ser, and
      Arg104-->Gln. Functional analysis of PVR in murine LM cells, stably expressing
      each of the PVR forms, showed that the PVR forms selected during persistent
      infection conferred on LM cells partial resistance to PV1/Mahoney-induced lysis.
      Although adsorption onto PVR seemed to be independent of the PVR form, an
      analysis of the conformational changes of the capsid during the early steps of
      the PV cycle provided evidence that the Ser39/Thr67 and Gln104 substitutions
      almost halved the conversion of 160S infectious particles into 135S A particles
      associated with the PV-PVR interaction. Altogether, these findings indicate that
      during persistent infection, specific mutations were selected in the domain 1 of
      PVR and that these mutations increased the resistance of cells to PV-induced
      lysis. These results are discussed in view of the position of the mutations on
      PVR.

PMID- 10964777
TI  - Related TT viruses in chimpanzees.
AB  - A series of serum specimens obtained from two chimpanzees experimentally infected
      with hepatitis A virus (HAV), hepatitis C virus, and hepatitis G/GB-C virus were
      tested for TT virus (TTV) by polymerase chain reaction (PCR). All PCR fragments
      obtained from both animals were directly sequenced, and the nucleotide sequences
      were compared to each other and to all known TTV sequences. This comparison
      showed that both animals were infected simultaneously with four new TTV variants
      designated A, M1, M2, and M3. One chimpanzee was found to be infected with TTV
      only after HAV inoculation, whereas the other animal was infected with TTV before
      any experimental procedure was performed. A set of PCR primers specific for these
      four new TTV variants was used to amplify TTV-like sequences from nine naive
      chimpanzees. None of these animals was infected with the prototype TTV variant.
      Two of these animals, however, were infected with one of the new TTV variants,
      while one animal was infected with an additional new TTV variant designated T.
      Among 99 hepatitis patients, 29 were found to be infected with the prototype TTV
      variant. None of these human specimens was found to be positive by PCR specific
      for TTV variants A, M1, M2, and M3. Similarly, not a single specimen from a
      smaller subset of human serum samples was found to be positive for the TTV
      variant T. Phylogenetic analysis performed on all known TTV sequences
      demonstrated that TTV can be classified into 13 different, yet closely related
      TTV species, designated as TTV-I for the prototype variant through TTV-XIII. The
      new variants M1 and M2 were classified as two different genotypes of TTV-VI,
      variant M3 was classified as TTV-VII, variant A was classified as TTV-VIII, and
      variant T was classified as TTV-IX. Thus, the data obtained in this study suggest
      that TTV represents a large swarm of TTV-like species, some of which have not
      been detected in humans and circulate predominantly among chimpanzees.

PMID- 10964778
TI  - An in vitro transcription system that recapitulates equine infectious anemia
      virus tat-mediated inhibition of human immunodeficiency virus type 1 Tat activity
      demonstrates a role for positive transcription elongation factor b and associated
      proteins in the mechanism of Tat activation.
AB  - Equine infectious anemia virus (EIAV) activates transcription via a Tat protein,
      a TAR element, and the equine elongation factor positive transcription elongation
      factor b (P-TEFb). In human cells, EIAV Tat (eTat) can inhibit the ability of
      human immunodeficiency virus type 1 (HIV-1) Tat (hTat) to activate transcription
      from the HIV-1 long terminal repeat, demonstrating that EIAV Tat can interact
      nonproductively with human P-TEFb. To study the mechanism of EIAV Tat and HIV-1
      Tat activation, we developed an in vitro elongation assay that recapitulates EIAV
      Tat-mediated inhibition of HIV-1 Tat trans-activation. We found that eTat
      specifically inhibits activation of elongation by HIV-1 Tat while having no
      effect on basal transcription elongation. The competitive inhibition of hTat
      activation was reversed by an activity present in HeLa cell nuclear extracts,
      most likely a form of P-TEFb. Recombinant P-TEFb (cyclin T1 and CDK9) overcame
      the inhibition of transcription by eTat but in a nonspecific manner. EIAV Tat
      affinity chromatography was used to purify the activity present in nuclear
      extract that was capable of reversing eTat inhibition. We characterized the
      protein components of this activity, which include cyclin T1, CDK9, Tat-SF1, and
      at least three unidentified proteins. These data suggest that additional factors
      are involved in the mechanism of Tat activation.

PMID- 10964779
TI  - Oligomerization and cell-binding properties of the avian reovirus cell-attachment
      protein sigmaC.
AB  - Avian reovirus protein sigmaC, the viral cell-attachment protein, is a minor
      component of the outer-capsid shell of the viral particle that is synthesized in
      small amounts in infected cells. We cloned the sigmaC-encoding ORF in vector pIL
      2f, expressed it in Escherichia coli, and partially purified the resulting
      recombinant protein from inclusion bodies. Rabbit polyclonal antibodies raised
      against the recombinant protein specifically recognized the viral polypeptide in
      ELISA, immunoprecipitation, and Western blotting. To study the oligomerization
      capacity and cell-binding affinity of protein sigmaC, the sigmaC-encoding ORF was
      also expressed in chicken embryo fibroblasts (CEFs) and in reticulocyte lysates.
      In all three systems protein sigmaC is expressed as a multimer with identical
      electrophoretic mobility to the naturally occurring protein. Cell-binding
      experiments show that both in vitro and in vivo expressed protein sigmaC display
      affinity for CEF receptors, and this property is exclusively associated with the
      oligomeric form of the protein. The fact that incubation of CEF cells with the
      recombinant protein expressed in bacterial cells completely blocks the binding of
      purified reovirions indicates both that binding of this protein to cells is
      specific and saturable, and that reovirions and protein sigmaC bind to the same
      class of cell receptor. Saturation binding experiments, performed with the
      recombinant protein expressed in E. coli and with purified reovirions, showed
      that the number of cellular receptor sites (CRSs) for avian reovirus S1133 is 1.8
      x 10(4) per CEF cell, whereas the number of cellular receptor units (CRUs) for
      sigmaC is 2.2 x 10(5) per CEF cell. These results are consistent with previous
      reports on the binding of mammalian reoviruses.

PMID- 10964780
TI  - HuR, a protein implicated in oncogene and growth factor mRNA decay, binds to the
      3' ends of hepatitis C virus RNA of both polarities.
AB  - To identify cellular factors that interact with hepatitis C virus RNA, cellular
      extracts were subjected to UV cross-linking to radiolabeled RNAs corresponding to
      the hepatitis C virus 5' and 3' untranslated regions of positive and negative
      polarities. Our results demonstrate that the U-rich region of the hepatitis C
      virus 3' untranslated region of the positive RNA strand is a hot spot for
      cellular RNA binding proteins. Two of these proteins were identified as the ELAV
      like HuR protein and hnRNP C. Interestingly, HuR and hnRNP C also interacted with
      the 3' end of the RNA representing the negative strand of the HCV genome. The
      binding of HuR and hnRNP C to the 3' ends of the HCV RNAs of both negative and
      positive polarities suggests that HuR and hnRNP C may be involved in the
      transcription of the HCV RNA genome. Alternatively, they act by protecting the
      HCV RNAs from premature degradation by binding to their 3' ends. However, we were
      unable to demonstrate an effect on HCV RNA stability by the HuR protein. These
      interactions may be necessary for the establishment of chronic active infections
      that may develop into cirrhosis or hepatocellular carcinoma.

PMID- 10964781
TI  - Identification of efficiently cleaved substrates for HIV-1 protease using a phage
      display library and use in inhibitor development.
AB  - The recognition sequences for substrate cleavage by aspartic protease of HIV-1
      are diverse and cleavage specificities are controlled by complex interactions
      between at least six amino acids around the cleavage site. We have identified 45
      efficiently cleaved peptide substrates of HIV-1 protease (PR) using substrate
      phage display, an approach that can elucidate both context-dependent and context
      independent preferences at individual subsites of a protease substrate. Many of
      the selected peptides were cleaved more efficiently and had lower K(m) values
      than physiologically relevant substrates of HIV-1 PR. Therefore, mutations
      occurring in the cleavage sites of the Gag and Gag-pol polyproteins of HIV-1
      could significantly lower the K(m) values to better compete against drugs for
      protease binding while maintaining cleavage rates necessary for viral
      replication. The most efficiently cleaved peptide substrate derived from these
      phage, Ac-GSGIF*LETSL-NH(2), was cleaved 60 times more efficiently and had a K(m)
      approximately 260 times lower than a nine-amino-acid peptide based on the natural
      reverse transcriptase/integrase cleavage site when assayed at pH 5.6, 0.2 M NaCl.
      The peptide substrates selected served as frameworks for synthesis of tight
      binding reduced amide inhibitors of HIV-1 PR. The results show that the most
      efficiently cleaved substrates serve as the best templates for synthesis of the
      tightest binding inhibitors. Thus, defining changes in substrate preferences for
      drug-resistant proteases may aid in the development of more efficacious
      inhibitors.

PMID- 10964782
TI  - Diversity of the HIV-1 long terminal repeat following mother-to-child
      transmission.
AB  - A study of the human immunodeficiency virus Type 1 (HIV-1) 5' long terminal
      repeat (LTR) was performed to determine the extent of variation found within the
      LTR from 19 mother-infant pairs in Tanzania and to assess whether the LTR is
      useful in distinguishing maternal sequences that were transmitted to infants. HIV
      1 subtypes A, C, and D as well as intersubtype recombinant LTR sequences were
      detected in mothers and infants. The LTR subtype was 100% concordant between
      mothers and their infants. Diversity calculations showed a significant reduction
      in LTR variation in infants compared to their mothers. However, the overall
      magnitude of LTR variation was less than that found in the env gene from the same
      individuals. These data suggest a selective constraint active upon the 5' long
      terminal repeat that is distinct from immune selective pressure(s) directed
      against HIV-1 structural genes. Detection of maternal LTR variants that were
      transmitted to infants may yield important information concerning nonstructural
      determinants of HIV-1 transmission from mother to infant.

PMID- 10964783
TI  - Differential effects of C-terminal molecular tagged integrase on replication
      competent moloney murine leukemia virus.
AB  - Moloney murine leukemia virus (M-MuLV) proviruses carrying integrase (IN) protein
      tagged either with a simian virus 40 (SV40) nuclear localization signal (NLS) or
      various antigenic epitopes were generated. Hexahistidine (His(6)), hemagluttinin
      (HA), or two consecutive HA sequences (2XHA) were fused to the C-terminus of IN
      as antigenic markers. These epitope-tagged IN proteins were stably expressed
      through multiple rounds of infection. The IN-His(6), IN-HA, and IN-2XHA proteins,
      purified from virus, could be immunoprecipitated with antibodies against His(6)
      and HA, respectively. An M-MuLV provirus encoding the SV40 large T antigen NLS
      fused to IN at the same position as the epitope tags was also passaged through
      cells. In contrast to the stability of the epitope tags, the SV40 NLS sequence
      was rapidly mutated by a frameshift mutation that introduced negatively charged
      amino acids into the basic NLS. The instability of the NLS suggests that the
      strong nuclear localization of the IN-SV40 NLS may have detrimental effects on
      virus assembly. These observations have implications for studying nuclear
      transport properties of M-MuLV and for engineering a murine-based retroviral
      vector for gene therapy.

PMID- 10964784
TI  - Sequence analysis of the leftward end of simian varicella virus (EcoRI-I
      fragment) reveals the presence of an 8-bp repeat flanking the unique long segment
      and an 881-bp open-reading frame that is absent in the varicella zoster virus
      genome.
AB  - Simian varicella virus (SVV) causes varicella (chickenpox) in nonhuman primates,
      becomes latent in cranial and dorsal root ganglia, and reactivates to produce
      zoster (shingles). Because the clinical and molecular features of SVV closely
      resemble those of varicella zoster virus (VZV) infection of humans, SVV infection
      of primates has served as an experimental model of VZV pathogenesis and latency.
      The SVV genome has been completely mapped, but attempts to clone the 3600-bp
      EcoRI fragment located at the leftward end of the virus genome have hitherto been
      unsuccessful. Herein, we report the cloning and the complete nucleotide sequence
      of this region. Comparison of the SVV and VZV sequences in this region revealed
      an 8-bp inverted repeat sequence flanking the unique long segment of the SVV
      genome; an 879-bp open-reading frame (ORF) A in SVV that is absent in VZV but has
      42% amino acid identity to SVV ORF 4 and 49% to VZV ORF 4; a 342-bp ORF B in SVV
      with 35% amino acid identity to a 387-bp ORF located to the left of ORF 1 on the
      VZV genome; and a 303-bp ORF in SVV with 27% amino acid identity to VZV ORF 1. No
      homologue of VZV ORF 2 was detected. Transcripts specific for ORFs A and B were
      present in SVV-infected cells in culture and in acutely infected monkey ganglia.
      Overall, there are more than 2000 bp of DNA in the SVV genome that are absent in
      the VZV genome.

PMID- 10964785
TI  - Exploiting polymerase promiscuity: A simple colorimetric RNA polymerase assay.
AB  - We developed a convenient colorimetric assay for monitoring RNA synthesis from
      DNA-dependent RNA polymerases (DdRp) and viral RNA-dependent RNA polymerases
      (RdRp). ATP and GTP with a p-nitrophenyl moiety attached to the gamma-phosphate
      were synthesized (PNP-NTPs). These PNP-NTPs can be used for RNA synthesis by
      several RNA polymerases, including the RdRps from brome mosaic virus and bovine
      viral diarrhea virus and the DdRps from bacteriophage T7 and SP6. When the
      polymerase reactions were performed in the presence of alkaline phosphatase,
      which digests the p-nitrophenylpyrophosphate side-product of phosphoryl transfer
      to the chromogenic p-nitrophenylate, an increase in absorbence at 405 nm was
      observed. These nucleotide analogues were used in continuous colorimetric
      monitoring of polymerase activity. Furthermore, the PNP-NTPs were found to be
      stable and utilized by RNA polymerases in the presence of human plasma. This
      simple colorimetric polymerase assay can be performed in a standard laboratory
      spectrophotometer and will be useful in screens for inhibitors of viral RNA
      synthesis.

PMID- 10964786
TI  - Spacing constraints on reinitiation of paramyxovirus transcription: the gene end
      U tract acts as a spacer to separate gene end from gene start sites.
AB  - The paramyxovirus gene end U tracts are thought to serve as templates for the
      addition of a 3' polyA tail to viral mRNAs. The goal of the work described here
      was to determine the function in transcription of the naturally occurring
      variability in length of the gene end U tracts of the paramyxovirus simian virus
      5 (SV5). An anchored RT-PCR assay was developed to test the hypothesis that the
      variable U tracts template the addition of variable lengths of polyA tails to
      mRNAs. The results showed that although the SV5 NP, M, and SH genes encode U
      tracts of seven, four, and six U residues, respectively, their mRNAs contain
      similar polyA tails of approximately 250-290 bases. These results indicate that
      the variable gene end U tracts are functionally equivalent in directing
      polyadenylation. A reverse genetics system based on a dicistronic minigenome
      containing the SH-HN gene junction was used to test the hypothesis that the
      variable U tracks affect the efficiency of transcription termination. Minigenome
      templates containing an SH gene end with a long U tract of six residues (U6)
      directed efficient transcription termination and reinitiation at the downstream
      HN start site with no nucleotide preference for the downstream intergenic region.
      Surprisingly, truncating the SH gene end U tract to four residues (U4) did not
      affect SH termination but, rather, reduced downstream HN reinitiation to 20-30%
      of wild-type levels. Efficient HN reinitiation could be restored to mutant U4
      templates in either of two ways: by increasing the U-tract length from four to
      six residues or by increasing the length of the intergenic region. Efficient HN
      reinitiation required a minimum of six bases between the last nucleotide in SH
      and the first nucleotide in HN. We propose that for some paramyxoviruses, the
      gene end U tract serves a previously unrecognized role as a spacer region between
      the gene end and gene start sites.

PMID- 10964787
TI  - Use of iodine for water disinfection: iodine toxicity and maximum recommended
      dose.
AB  - Iodine is an effective, simple, and cost-efficient means of water disinfection
      for people who vacation, travel, or work in areas where municipal water treatment
      is not reliable. However, there is considerable controversy about the maximum
      safe iodine dose and duration of use when iodine is ingested in excess of the
      recommended daily dietary amount. The major health effect of concern with excess
      iodine ingestion is thyroid disorders, primarily hypothyroidism with or without
      iodine-induced goiter. A review of the human trials on the safety of iodine
      ingestion indicates that neither the maximum recommended dietary dose (2 mg/day)
      nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather
      than a clear threshold response level or a linear and temporal dose-response
      relationship between iodine intake and thyroid function, there appears to be
      marked individual sensitivity, often resulting from unmasking of underlying
      thyroid disease. The use of iodine for water disinfection requires a risk-benefit
      decision based on iodine's benefit as a disinfectant and the changes it induces
      in thyroid physiology. By using appropriate disinfection techniques and
      monitoring thyroid function, most people can use iodine for water treatment over
      a prolonged period of time.

PMID- 10964790
TI  - Chemical characterization and bioactivity of polycyclic aromatic hydrocarbons
      from non-oxidative thermal treatment of pyrene-contaminated soil at 250-1,000
      degrees C.
AB  - In this paper we report yields, identities, and mutagenicities of products from
      heating a polycyclic aromatic hydrocarbon (PAH)-contaminated, Superfund-related
      synthetic soil matrix without exogenous oxygen. We heated batch samples of soil
      pretreated with 5.08 wt% (by weight) pyrene in a tubular furnace under a constant
      flow of helium gas at 250, 500, 750, and 1,000 +/- 20 degrees C. Dichloromethane
      (DCM) extracts of cooled residues of heated soil and of volatiles condensed on a
      cold finger after 1 sec residence time at furnace temperature were assayed
      gravimetrically and analyzed for PAH by HPLC, HPLC coupled to mass spectrometry,
      and gas chromatography coupled to mass spectrometry. All four temperatures
      volatilized pyrene and generated other PAHs, including alkylated pyrenes. We
      detected bioactive PAHs in the product volatiles: cyclopenta[cd]pyrene (CPP) at
      750 and 1,000 degrees C and benzo[a]pyrene (BaP) at 1,000 degrees C. We found a
      clean soil residue, i.e., no pyrene or other DCM extracts, only at 750 degrees C.
      Control experiments with uncontaminated soil, pyrene, and Ottawa sand plus 4.89
      wt% pyrene revealed no CPP or BaP production from soil itself, but these
      experiments imply that pyrene interactions with soil, e.g., soil-bound silica,
      stimulate CPP and BaP production. We detected mutagenicity to human diploid
      lymphoblasts (in vitro) in volatiles from 1,000 degrees C heating of soil plus
      pyrene and sand plus pyrene, and in the residue from 500 degrees C heating of
      soil plus pyrene. Three plausible pathways for pyrene conversion to other PAHs
      are a) a reaction with light gas species, e.g., soil- or pyrene-derived
      acetylene; b) loss of C(2)-units followed by reaction with a PAH; and c)
      dimerization with further molecular weight growth via cyclodehydrogenation. This
      study shows that thermal treatment of PAH-polluted soil may generate toxic by
      products that require further cleanup by oxidation or other measures.

PMID- 10964789
TI  - Genistein: does it prevent or promote breast cancer?
AB  - Diet is estimated to contribute to approximately 50% of all newly diagnosed
      breast cancers. As such, a search for dietary factors differentially consumed
      among populations with increased breast cancer risk (e.g., Caucasians) compared
      to those with low risk (e.g., Asians) has become a priority. One such dietary
      component, which is typical to the Asian but not the Caucasian diet, is soy. We
      review data relevant to attempts to determine whether soy, and more specifically
      genistein, is a dietary component that may help to explain the dramatic disparity
      in breast cancer risk among these populations.

PMID- 10964788
TI  - Concentrated swine feeding operations and public health: a review of occupational
      and community health effects.
AB  - Recent industry changes in swine-management practices have resulted in a growing
      controversy surrounding the environmental and public health effects of modern
      swine production. The numerous wastes produced by intensive swine production not
      only pose a significant challenge to effective environmental management but also
      are associated with decreased air quality in confinement houses, potentially
      transferable antimicrobial resistance patterns, and several infectious agents
      that can be pathogenic to humans. Published studies have documented a variety of
      contaminants, microbial agents, and health effects in those occupationally
      exposed to swine, and these have provided the groundwork for an increasing body
      of research to evaluate possible community health effects. Nonetheless, several
      factors limit our ability to define and quantify the potential role of intensive
      swine-rearing facilities in occupational and community health. Our incomplete
      understanding and ability to detect specific exposures; the complicated nature of
      disease etiology; pathogenesis; and surveillance; and the inherent difficulties
      associated with study design all contribute to the inadequate level of knowledge
      that currently prevails. However; an evaluation of the published literature; and
      a recognition of the elements that may be compromising these studies; provides
      the foundation from which future studies may develop.

PMID- 10964791
TI  - Both the environment and genes are important for concentrations of cadmium and
      lead in blood.
AB  - Concentrations of cadmium and lead in blood (BCd and BPb, respectively) are
      traditionally used as biomarkers of environmental exposure. We estimated the
      influence of genetic factors on these markers in a cohort of 61 monozygotic and
      103 dizygotic twin pairs (mean age = 68 years, range = 49-86). BCd and BPb were
      determined by graphite furnace atomic absorption spectrophotometry. Variations in
      both BCd and BPb were influenced by not only environmental but also genetic
      factors. Interestingly, the genetic influence was considerably greater for
      nonsmoking women (h(2) = 65% for BCd and 58% for BPb) than for nonsmoking men (13
      and 0%, respectively). The shared familial environmental (c(2)) influence for BPb
      was 37% for men but only 3% for women. The association between BCd and BPb could
      be attributed entirely to environmental factors of mutual importance for levels
      of the two metals. Thus, blood metal concentrations in women reflect not only
      exposure, as previously believed, but to a considerable extent hereditary factors
      possibly related to uptake and storage. Further steps should focus on
      identification of these genetic factors and evaluation of whether women are more
      susceptible to exposure to toxic metals than men.

PMID- 10964793
TI  - Longitudinal investigation of exposure to arsenic, cadmium, and lead in drinking
      water.
AB  - Arsenic, cadmium, and lead have been associated with various forms of cancer,
      nephrotoxicity, central nervous system effects, and cardiovascular disease in
      humans. Drinking water is a well-recognized pathway of exposure to these metals.
      To improve understanding of the temporal dimension of exposure to As, Cd, and Pb
      in drinking water, we obtained 381 samples of tap and/or tap/filtered water and
      self-reported rates of drinking water consumption from 73 members of a stratified
      random sample in Maryland. Data were collected at approximately 2-month intervals
      from September 1995 through September 1996. Concentrations of As (range < 0.2
      13.8 microg/L) and Pb (< 0.1-13.4 microg/L) were within the ranges reported for
      the United States, as were the rates of drinking water consumption (median < 0.1
      4.1 L/day). Cd was present at a detectable level in only 8.1% of the water
      samples. Mean log-transformed concentrations and exposures for As and Pb varied
      significantly among sampling cycles and among respondents, as did rates of
      drinking water consumption, according to a generalized linear model that
      accounted for potential correlation among repeated measures from the same
      respondent. We used the intraclass correlation coefficient of reliability to
      attribute the total variance observed for each exposure metric to between-person
      and within-person variability. Between-person variability was estimated to
      account for 67, 81, and 55% of the total variance in drinking water consumption,
      As exposure (micrograms per day), and Pb exposure (micrograms per day),
      respectively. We discuss these results with respect to their implications for
      future exposure assessment research, quantitative risk assessment, and
      environmental epidemiology.

PMID- 10964792
TI  - Quantitative comparisons of in vitro assays for estrogenic activities.
AB  - Substances that may act as estrogens show a broad chemical structural diversity.
      To thoroughly address the question of possible adverse estrogenic effects,
      reliable methods are needed to detect and identify the chemicals of these diverse
      structural classes. We compared three assays--in vitro estrogen receptor
      competitive binding assays (ER binding assays), yeast-based reporter gene assays
      (yeast assays), and the MCF-7 cell proliferation assay (E-SCREEN assay)--to
      determine their quantitative agreement in identifying structurally diverse
      estrogens. We examined assay performance for relative sensitivity, detection of
      active/inactive chemicals, and estrogen/antiestrogen activities. In this
      examination, we combined individual data sets in a specific, quantitative data
      mining exercise. Data sets for at least 29 chemicals from five laboratories were
      analyzed pair-wise by X-Y plots. The ER binding assay was a good predictor for
      the other two assay results when the antiestrogens were excluded (r(2) is 0.78
      for the yeast assays and 0.85 for the E-SCREEN assays). Additionally, the
      examination strongly suggests that biologic information that is not apparent from
      any of the individual assays can be discovered by quantitative pair-wise
      comparisons among assays. Antiestrogens are identified as outliers in the ER
      binding/yeast assay, while complete antagonists are identified in the ER binding
      and E-SCREEN assays. Furthermore, the presence of outliers may be explained by
      different mechanisms that induce an endocrine response, different impurities in
      different batches of chemicals, different species sensitivity, or limitations of
      the assay techniques. Although these assays involve different levels of biologic
      complexity, the major conclusion is that they generally provided consistent
      information in quantitatively determining estrogenic activity for the five data
      sets examined. The results should provide guidance for expanded data mining
      examinations and the selection of appropriate assays to screen estrogenic
      endocrine disruptors.

PMID- 10964794
TI  - Cardiac autonomic control mechanisms in power-frequency magnetic fields: a
      multistudy analysis.
AB  - Heart rate variability (HRV), a noninvasive indicator of autonomic control of
      cardiac activity, is predictive of long-term cardiac morbidity and mortality.
      Epidemiologic research suggests that occupational exposure to power-frequency
      magnetic fields may be associated with autonomically mediated cardiac mortality.
      Results from our laboratory studies of humans exposed to 60-Hz magnetic fields
      overnight, however, are inconsistent. HRV is altered in some studies but not
      others. To clarify this, the pooled data from seven studies involving 172 men
      were analyzed to test specific hypotheses concerning this inconsistency. After
      analysis, we excluded a) measurement drift or instability over time because HRV
      was stable under sham-exposed conditions across all studies; b) inadequate
      statistical power or failure to maintain double-blind controls; c) differences in
      field intensity (28.3 vs. 127.3 microT) or exposure pattern (intermittent versus
      continuous) as main effects; or d) the inclusion of individuals sensitive to
      magnetic field exposure in some studies but not others. Four separate analytic
      techniques failed to identify a valid subpopulation of sensitive individuals. In
      some studies, however, hourly blood samples were collected using an indwelling
      venous catheter. HRV alterations occurred during intermittent exposure in these
      studies (p < 0.05) but not in similar studies without blood sampling. This result
      suggests a field interaction with modest arousal or disturbance. Because HRV is
      tightly coupled to electroencephalographic activity during sleep, these results
      are physiologically plausible and suggest that HRV alterations during exposure to
      magnetic fields may occur when accompanied by increases in physiologic arousal,
      stress, or sleep disturbance.

PMID- 10964795
TI  - The effects of internal radiation exposure on cancer mortality in nuclear workers
      at Rocketdyne/Atomics International.
AB  - We examined the effects of chronic exposure to radionuclides, primarily uranium
      and mixed-fission products, on cancer mortality in a retrospective cohort study
      of workers enrolled in the radiation-monitoring program of a nuclear research and
      development facility. Between 1950 and 1994, 2,297 workers were monitored for
      internal radiation exposures, and 441 workers died, 134 (30.4%) of them from
      cancer as the underlying cause. We calculated internal lung-dose estimates based
      on urinalysis and whole-body and lung counts reported for individual workers. We
      examined cancer mortality of workers exposed at different cumulative lung-dose
      levels using complete risk-set analysis for cohort data, adjusting for age, pay
      type, time since first radiation monitored, and external radiation. In addition,
      we examined the potential for confounding due to chemical exposures and smoking,
      explored whether external radiation exposure modifies the effects of internal
      exposure, and estimated effects after excluding exposures likely to have been
      unrelated to disease onset. Dose-response relations were observed for death from
      hemato- and lymphopoietic cancers and from upper aerodigestive tract cancers,
      adjusting for age, time since first monitored, pay type, and external (gamma)
      radiation dose. No association was found for other cancers, including cancers of
      the lung. Despite the small number of exposed deaths from specific cancer types
      and possible bias due to measurement error and confounding, the positive findings
      and strong dose-response gradients observed suggest carcinogenic effects of
      internal radiation to the upper aerodigestive tract and the blood and lymph
      system in this occupational cohort. However, causal inferences require
      replication of our results in other populations or confirmation with an extended
      follow-up of this cohort.

PMID- 10964796
TI  - Controlled human exposure to methyl tertiary butyl ether in gasoline: symptoms,
      psychophysiologic and neurobehavioral responses of self-reported sensitive
      persons.
AB  - The 1990 Clean Air Act mandated oxygenation of gasoline in regions where carbon
      monoxide standards were not met. To achieve this standard, methyl tertiary butyl
      ether (MTBE) was increased to 15% by volume during winter months in many
      locations. Subsequent to the increase of MTBE in gasoline, commuters reported
      increases in symptoms such as headache, nausea, and eye, nose, and throat
      irritation. The present study compared 12 individuals selected based on self
      report of symptoms (self-reported sensitives; SRSs) associated with MTBE to 19
      controls without self-reported sensitivities. In a double-blind, repeated
      measures, controlled exposure, subjects were exposed for 15 min to clean air,
      gasoline, gasoline with 11% MTBE, and gasoline with 15% MTBE. Symptoms, odor
      ratings, neurobehavioral performance on a task of driving simulation, and
      psychophysiologic responses (heart and respiration rate, end-tidal CO(2), finger
      pulse volume, electromyograph, finger temperature) were measured before, during,
      and immediately after exposure. Relative to controls, SRSs reported significantly
      more total symptoms when exposed to gasoline with 15% MTBE than when exposed to
      gasoline with 11% MTBE or to clean air. However, these differences in symptoms
      were not accompanied by significant differences in neurobehavioral performance or
      psychophysiologic responses. No significant differences in symptoms or
      neurobehavioral or psychophysiologic responses were observed when exposure to
      gasoline with 11% MTBE was compared to clean air or to gasoline. Thus, the
      present study, although showing increased total symptoms among SRSs when exposed
      to gasoline with 15% MTBE, did not support a dose-response relationship for MTBE
      exposure nor the symptom specificity associated with MTBE in epidemiologic
      studies.

PMID- 10964797
TI  - Association between chlorination of drinking water and adverse pregnancy outcome
      in Taiwan.
AB  - Chlorination has been the major means of disinfecting drinking water in Taiwan.
      The use of chlorinated water has been hypothesized to lead to several adverse
      birth outcomes, including low birth weight and preterm delivery. We performed a
      study to examine the relationship between the use of chlorinated water and
      adverse birth outcomes in Taiwan. The study areas included 14 chlorinating
      municipalities (CHMs), which were defined as municipalities in which > 90% of the
      municipal population was served by chlorinated water, and 14 matched
      nonchlorinating municipalities (NCHMs), defined as municipalities in which < 5%
      of the municipal population is served by chlorinated water. The CHMs and NCHMs
      were similar to one another in terms of level of urbanization and
      sociodemographic characteristics. The study population comprised 18,025 women
      residing in the 28 municipalities who had a first parity singleton birth between
      1 January 1994 and 31 December 1996 and for which complete information on
      maternal age, education, gestational age, birth weight, and sex of the baby were
      available. The results of our study suggest that there was no association between
      consumption of chlorinated drinking water and the risk of low birth weight.

PMID- 10964798
TI  - Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory
      (StAR) protein expression.
AB  - Recent reports demonstrate that many currently used pesticides have the capacity
      to disrupt reproductive function in animals. Although this reproductive
      dysfunction is typically characterized by alterations in serum steroid hormone
      levels, disruptions in spermatogenesis, and loss of fertility, the mechanisms
      involved in pesticide-induced infertility remain unclear. Because testicular
      Leydig cells play a crucial role in male reproductive function by producing
      testosterone, we used the mouse MA-10 Leydig tumor cell line to study the
      molecular events involved in pesticide-induced alterations in steroid hormone
      biosynthesis. We previously showed that the organochlorine insecticide lindane
      and the organophosphate insecticide Dimethoate directly inhibit steroidogenesis
      in Leydig cells by disrupting expression of the steroidogenic acute regulatory
      (StAR) protein. StAR protein mediates the rate-limiting and acutely regulated
      step in steroidogenesis, the transfer of cholesterol from the outer to the inner
      mitochondrial membrane where the cytochrome P450 side chain cleavage (P450scc)
      enzyme initiates the synthesis of all steroid hormones. In the present study, we
      screened eight currently used pesticide formulations for their ability to inhibit
      steroidogenesis, concentrating on their effects on StAR expression in MA-10
      cells. In addition, we determined the effects of these compounds on the levels
      and activities of the P450scc enzyme (which converts cholesterol to pregnenolone)
      and the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme (which converts
      pregnenolone to progesterone). Of the pesticides screened, only the pesticide
      Roundup inhibited dibutyryl [(Bu)(2)]cAMP-stimulated progesterone production in
      MA-10 cells without causing cellular toxicity. Roundup inhibited steroidogenesis
      by disrupting StAR protein expression, further demonstrating the susceptibility
      of StAR to environmental pollutants.

PMID- 10964799
TI  - Air pollution and daily mortality in three U.S. counties.
AB  - I used generalized additive models to analyze the time-series of daily total
      nonaccidental and cause-specific (cardiovascular, cerebrovascular, and chronic
      obstructive pulmonary disease) deaths over the period 1987-1995 in three major
      U.S. metropolitan areas: Cook County, Los Angeles County, and Maricopa County. In
      all three counties I had monitoring information on particulate matter [less
      than/equal to] 10 microm (PM(10)), carbon monoxide, sulfur dioxide, nitrogen
      dioxide, and ozone. In Los Angeles, monitoring information on particulate matter
      [less than/equal to] 2.5 microm (PM(2.5)) was available as well. I present the
      results of both single and multi-pollutant analyses. Air pollution was associated
      with each of the mortality end points. With respect to the individual components
      of the pollution mix, the results indicate considerable heterogeneity of air
      pollution effects in the different geographic locations. In general, the gases,
      particularly CO, but not ozone, were much more strongly associated with mortality
      than was particulate matter. This association was particularly striking in Los
      Angeles County.

PMID- 10964800
TI  - Learning disabilities association-sponsored symposium on chemical hormone
      impostors and child development.

PMID- 10964801
TI  - Farmworkers and pesticides: community-based research.
AB  - In this paper we summarize the results of a workshop conducted to disseminate
      information about community-based research on the environmental health risks of
      exposure of farmworkers to pesticides. Community-based research is an approach
      that is advocated for addressing issues of environmental justice such as exposure
      of farmworkers to pesticides. This workshop brought together scientists,
      community organization members, and agency representatives to review and discuss
      the research methods and organizational relationships that have been successful
      in conducting past community research so these principles can be applied to new
      situations. The objectives of this workshop were to a) be a forum in which those
      conducting community-based research with farmworkers could share what they had
      learned; b) delineate the successes and barriers across different projects to
      further develop models and methods for conducting community-based research; and
      c) determine future directions and needs of farmworker community-based research
      for environmental justice.

PMID- 10964803
TI  - The developing role of ecotoxicology in industrial ecology and natural
      capitalism.

PMID- 10964802
TI  - Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl
      chloride monomer.
AB  - Various malignant tumors of the liver, especially liver angiosarcoma, have been
      described after occupational exposure to vinyl chloride monomer. We present the
      case records and pathologic findings of two plastic industry workers who had been
      exposed to high concentrations of vinyl chloride. These workers developed hepatic
      neoplasms, angiosarcoma, or hemangiopericytoma. We discuss the histogenesis of
      these tumors; the common vascular origin and the mutual transformation of these
      two tumors suggest that the hemangiopericytoma may also have developed during
      occupational exposure to high concentrations of vinyl chloride monomer.

PMID- 10964804
TI  - Making amends: ecological restoration in the United States.
AB  - Restoring an ecosystem to its preindustrial state can be very difficult or
      impossible. The great majority of restoration projects put a high priority on the
      biological requirements of endangered species, often drawing ecologists into
      volatile political controversies over the rights of humans versus those of
      wildlife. Meanwhile, resource managers struggle to gain enough information about
      historical ecosystems to reconstruct them successfully. There are often difficult
      judgment calls when scientists try to redesign a system that has been degraded
      over many generations, and it's often confusing to decide which period of history
      to restore an ecosystem to. In addition, modern industrialized society continues
      to place extensive demands upon already-stressed, degraded ecosystems.
      Restoration projects in the Florida Everglades, Pacific Northwest riverine
      systems, and forests in the Southeast illustrate the challenges associated with
      ecological restoration.

PMID- 10964805
TI  - The Kyoto protocol: just a lot of hot air.

PMID- 10964806
TI  - Recycling poultry feathers: more bang for the cluck.

PMID- 10964807
TI  - Lattice corneal dystrophy.

PMID- 10964809
TI  - Letter to the editor

PMID- 10964810
TI  - Author's reply

PMID- 10964808
TI  - Prophylactic intracameral vancomycin and CME.

PMID- 10964811
TI  - Letter to the editor

PMID- 10964812
TI  - Author's reply

PMID- 10964813
TI  - Author's reply

PMID- 10964814
TI  - Cataract formation after silicone PCL implantation.

PMID- 10964815
TI  - Andreas Vesalius.

PMID- 10964816
TI  - Photoscreening.

PMID- 10964817
TI  - Refractive surgery and the glaucoma patient. Customized corneas under pressure.

PMID- 10964818
TI  - Screening for amblyopia in preverbal children with photoscreening photographs:
      II. Sensitivity and specificity of the MTI photoscreener.
AB  - OBJECTIVE: To determine the sensitivity and specificity of vision screening using
      the Medical Technology and Innovations (MTI), Inc., PhotoScreener. DESIGN: Cross
      sectional study. PARTICIPANTS AND TESTING: Three hundred ninety-two children less
      than 4 years of age received a complete ophthalmologic examination and were
      photographed using the MTI PhotoScreener. One hundred three children had normal
      examinations, and the remaining 284 children had conditions of interest for
      pediatric screening: ptosis, media opacity, refractive error, or strabismus. Five
      children were excluded. MAIN OUTCOME MEASURES: The grading of the photographs by
      the manufacturer's representative was compared with the results of the
      ophthalmologic examinations. Sensitivity and specificity of vision screening were
      determined. RESULTS: The analysis of all informative photographs resulted in a
      sensitivity of 65% and a specificity of 87%. The sensitivity of detection for
      children with some forms of strabismus was high, up to 95% for esotropia of
      10Delta or more. Sensitivities for the detection of ptosis, media opacity, and
      refractive error were poor in patients where strabismus was not also present.
      CONCLUSIONS: The MTI PhotoScreener may play a role in preverbal vision screening;
      identification of two of three children with amblyopiogenic factors before age 4
      would be an exciting advance in public health. However, improvement in the
      ability to identify children with media opacity and refractive error is
      necessary. Improvements may be possible with modifications of the examination
      failure and photograph grading criteria.

PMID- 10964819
TI  - Screening for amblyopia in preverbal children with photoscreening photographs.
      III. improved grading criteria for hyperopia.
AB  - OBJECTIVE: To examine the ability of the Medical Technology and Innovations
      (MTI), Inc., Photoscreener (Cedar Falls, IA) to detect hyperopia and to improve
      the photograph grading criteria to screen for amblyopiogenic levels of hyperopia.
      DESIGN: Cross-sectional study and reanalysis. PARTICIPANTS AND TESTING: In
      previous work, 392 participants received a complete ophthalmologic examination
      and were photographed using the MTI Photoscreener. For this study, all 209
      participants with normal examination findings (65 children) or hyperopia without
      anisometropia (144 children) were selected. The data were reanalyzed using
      modified photograph grading and ophthalmologic examination failure criteria.
      Potential reasons for why many children with hyperopia passed photoscreening were
      explored. MAIN OUTCOME MEASURES: We determined whether a study participant would
      pass or fail screening with a given photograph grading and ophthalmologic
      examination failure criteria. RESULTS: Most children with hyperopia of +2.00 to
      +3.50 diopters (D) passed screening with the MTI instrument, in most cases
      because their photographs lacked bright crescents. When bright crescents in at
      least two of the four possible meridians were the grading guideline for screening
      failure and the pediatric ophthalmologists' consensus hyperopia failure criteria
      (> +3.50 D) were adopted, the sensitivity for hyperopia detection was 100% and
      the specificity was 88%. Identical results were obtained using the American
      Academy of Ophthalmology Preferred Practice Pattern hyperopia failure criteria
      (>/= +4.50 D). CONCLUSIONS: The MTI photograph grading guidelines can be
      simplified, and the ophthalmologic examination failure criteria for hyperopia can
      be improved. The presence of a bright crescent in the lower or the left pupillary
      margin indicate hyperopia in an amblyopiogenic range (> +3.50 D).

PMID- 10964821
TI  - Screening for amblyogenic factors using a volunteer lay network and the MTI
      PhotoScreener

PMID- 10964820
TI  - Screening for amblyogenic factors using a volunteer lay network and the MTI
      photoscreener. Initial results from 15,000 preschool children in a statewide
      effort.
AB  - PURPOSE: To describe the results from a statewide preschool vision screening
      program using the MTI PhotoScreener (Medical Technology and Innovations, Inc.,
      Cedar Falls, IA). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 15,059
      children aged 6 to 47 months enrolled in childcare and preschool settings
      throughout the state of Tennessee. METHODS: Volunteers from local Lions Clubs
      took photoscreening photographs of children in a statewide effort. Photographs
      were interpreted at the Vanderbilt Ophthalmic Photography Reading Center using
      predetermined criteria. Children who failed the screening were referred to
      community ophthalmologists or optometrists who performed a comprehensive
      evaluation and forwarded the results to the authors. MAIN OUTCOME MEASURES:
      Referral rate, unreadable rate, and predictive value positive (PVP). RESULTS:
      During the 2 years of the screening program, 15,059 children were screened in 850
      screenings. The screening referred 1013 children (6.7%), and 704 photographs
      (4.7%) were unreadable. Children who failed the screening had a significant
      abnormality (strabismus, anisometropia, high hypermetropia, high astigmatism, or
      high myopia) in 320 of the 531 cases where adequate follow-up results were
      reported. The PVP ranged from 84% when a diagnosis of strabismus was suggested by
      the photoscreen reading to 41% for astigmatism. Despite intense attention to
      follow-up, many children who failed the screening never received a formal eye
      examination. CONCLUSIONS: The MTI PhotoScreener can be used by volunteers to
      screen preschool children and can have a high PVP in organized settings, provided
      that meticulous attention is paid to photograph interpretation and quality
      control. The PVP of the MTI PhotoScreener depends on the diagnosis suggested when
      the photograph is read. Significant obstacles exist in obtaining care for those
      who fail screening.

PMID- 10964822
TI  - High levels of binocular function are achievable after removal of monocular
      cataracts in children before 8 years of age.
AB  - OBJECTIVE: To investigate the visual acuity and binocular function results
      achieved in children who had monocular cataracts removed before 8 years of age.
      DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Clinical records
      of 171 patients who underwent a unilateral cataract removal between January 1986
      and 1996 were reviewed retrospectively. Seventy-four eyes were included in the
      study: 19 congenital, 11 developmental, 19 posterior lenticonus, 19 traumatic,
      and 6 complicated cataracts. Patients with less than 2 years of follow-up; eyes
      with cataracts resulting from retinoblastoma; prematurity; and those associated
      with dense corneal scars, lens dislocation, and persistent hyperplastic primary
      vitreous were excluded. INTERVENTION: Visual acuity was measured by means of age
      appropriate tests such as the fixation pattern, Allen object recognition cards,
      isolated optotypes with the Sheridan Gardiner test, and Snellen letters. Sensory
      fusion was assessed with the Worth 4-dot test, and stereo acuity was assessed
      with the Titmus stereo test. MAIN OUTCOME MEASURES: Cataracts were classified
      regarding type, extent, age at onset, duration of the opacity, age at surgery,
      method of removal, development of secondary membrane, form of optical
      rehabilitation, and presence of strabismus. Visual acuity levels between 6/6 and
      6/12 were considered "good." Fusion of the Worth 4-dot test at distance and near,
      and presence of stereo acuity of 100 seconds of arc or better were considered
      "good" binocular function. Multiple logistic regression analysis was used to
      define factors that correlated with achieving good visual outcome. RESULTS:
      Visual acuity was 6/12 or better in 27 (36.5%) eyes. However, good binocular
      function was achieved in only 11 of these 27 patients. Results of univariate
      analysis showed that later age at onset of cataract and absence of strabismus
      were significant for good visual acuity and binocular function. The presence of
      strabismus increases the risk of not achieving good visual acuity by 5.45-fold.
      CONCLUSIONS: Good visual acuity and binocular function can be achieved after
      removal of monocular cataracts in visually immature children. Patients with
      strabismus at presentation or during the follow-up period have the least chance
      of achieving a good sensory result.

PMID- 10964823
TI  - Postcontrast magnetic resonance imaging assessment of porous polyethylene orbital
      implant (Medpor).
AB  - OBJECTIVE: To evaluate the fibrovascular ingrowth progression within the porous
      polyethylene orbital implant (Medpor) with serial magnetic resonance imaging
      (MRI). DESIGN: Prospective, nonrandomized, comparative (self-controlled) trial.
      PARTICIPANTS: Ten patients who underwent enucleation and implantation of a 20-mm
      porous polyethylene implant wrapped with heterologous sclera. METHODS: Serial
      precontrast and postcontrast T1-weighted MRI were obtained at 1.5, 3, 6, and 12
      months after implantation. The percentage area of enhancement was calculated by
      use of manual planimetric contouring unenhanced areas at the equator of each
      sphere on axial and coronal planes. RESULTS: All the implants showed enhancing
      areas as early as 1.5 months after enucleation. In 8 of the 10 patients, the
      areas of enhancement at the equator of the implant consistently showed similar
      centripetal progression primarily during the first 6 months after enucleation.
      The presence of fibrovascular tissue at the equator was associated in all cases
      with enhancing zones at the anterior portion of the implant. None of the implants
      showed diffuse complete enhancement after 12 months. Two patients failed to
      demonstrate further enhancement progression 1.5 months after implantation. No
      histopathologic study to equate with the MRI findings was performed in this
      series. CONCLUSIONS: Postcontrast magnetic resonance studies seem to be the best
      suited imaging modality for assessing the fibrovascular tissue progression into
      porous polyethylene spheres after enucleation and for identifying patients in
      whom failure of vascularization occurs. Incomplete vascularization at the equator
      of the porous polyethylene sphere does not prove an absence of fibrovascular
      ingrowth in the anterior region. Prior ocular surgery and coexisting arterial
      hypertension may slow the progression of fibrovascular ingrowth.

PMID- 10964824
TI  - Primary implant placement with evisceration in patients with endophthalmitis.
AB  - OBJECTIVE: To evaluate the efficacy of primary orbital implant placement with
      evisceration in patients with endophthalmitis and blind eyes. DESIGN:
      Retrospective noncomparative case series. PARTICIPANTS: Eleven patients with
      endophthalmitis and blind eyes underwent evisceration by two surgeons between
      1994 and 1998. INTERVENTION: Evisceration and primary orbital implant placement.
      MAIN OUTCOME MEASURES: All patients were evaluated for implant exposure and
      successful fitting of their prostheses. RESULTS: Ten of 11 patients had
      uneventful postoperative courses and successful prosthetic fitting. One patient
      with Pseudomonas aeruginosa endophthalmitis had an implant exposure successfully
      treated with a fascia lata patch. CONCLUSIONS: Primary orbital implant placement
      with evisceration in patients with endophthalmitis is an acceptable treatment,
      eliminating the need for open evisceration and subsequent delayed orbital implant
      placement.

PMID- 10964825
TI  - Primary implant placement with evisceration

PMID- 10964826
TI  - Clinical efficacy of the polyurethane stent without fluoroscopic guidance in the
      treatment of nasolacrimal duct obstruction.
AB  - PURPOSE: To evaluate the clinical efficacy of the polyurethane (Song) stent in
      the treatment of nasolacrimal duct obstruction without fluoroscopic guidance,
      especially at the junction between the lacrimal sac and nasolacrimal duct or at
      the nasolacrimal duct. DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: This study evaluated 59 cases of nasolacrimal duct obstruction in
      53 patients, with mean epiphora of 36 months (range, 2 months-17 years). METHODS:
      Without the assistance of a radiologist, a polyurethane nasolacrimal stent was
      placed by introducing a guidewire through the superior or inferior punctum into
      the canaliculus and advancing it across the obstruction into the opening of the
      inferior meatus of the nasal cavity. The mean follow-up period was 22 months
      (range, 12 months-48 months). MAIN OUTCOME MEASURES: Patency of the lacrimal
      passage to irrigation and the duration of this procedure. RESULTS: Complete
      resolution of epiphora was accomplished in 55 (93.2%) of the 59 eyes. There was
      recurrence of epiphora in four cases because of obstruction of the stent in three
      cases and obstruction of the common canaliculus by recurrent dacryocystitis in
      one case. CONCLUSIONS: Polyurethane stenting without fluoroscopic guidance seems
      to be a valuable technique for primary management of nasolacrimal duct
      obstruction before dacryocystorhinostomy.

PMID- 10964827
TI  - Nonpenetrating deep sclerectomy versus trabeculectomy in bilateral primary open
      angle glaucoma.
AB  - OBJECTIVE: To establish the efficacy and safety of nonpenetrating deep
      sclerectomy versus trabeculectomy in primary open-angle glaucoma. DESIGN:
      Prospective randomized trial. PARTICIPANTS: Thirty-nine patients (78 eyes) with
      bilateral primary open angle glaucoma were included in the study. INTERVENTION:
      Eyes were randomly assigned to receive deep sclerectomy in one eye and
      trabeculectomy in the other eye. MAIN OUTCOME MEASURES: Mean intraocular pressure
      (IOP), postoperative medications, visual acuity, success rate, and complications.
      RESULTS: At 12 months, mean IOP reduction was 12.3 +/- 4.2 (sclerectomy) versus
      14.1 +/- 6.4 mmHg (trabeculectomy) (P = 0.15), and an IOP </= 21 mmHg was
      achieved in 36 (92.3%) and 37 eyes (94.9%) (P = 0.9), respectively. Complications
      included three (7.7%) flat/shallow anterior chambers and one (2.6%) hypotony
      (trabeculectomy), whereas internal iris incarceration was encountered in two eyes
      (5.1%) (sclerectomy). CONCLUSIONS: Deep sclerectomy may provide comparable IOP
      reduction with fewer complications in management of primary open angle glaucoma.

PMID- 10964828
TI  - Autologous conjunctival resurfacing of leaking filtering blebs.
AB  - PURPOSE: To present a case series of a new technique to repair late bleb leaks.
      DESIGN: Retrospective, noncomparative, consecutive case series. PARTICIPANTS:
      Forty-seven autologous conjunctival resurfacings of late bleb leaks were
      performed by four surgeons at two institutions. METHODS: Autologous conjunctival
      grafts were placed over existing de-epithelialized leaking blebs. MAIN OUTCOME
      MEASURES: Leak-free, Seidel-negative blebs and controlled glaucoma. RESULTS:
      After a mean follow-up of 14 +/- 12 months, one patient continued to have bleb
      leak at the last follow-up, and one frank leak resolved with aqueous suppression.
      Intraocular pressure increased from 6.6 +/- 4.4 mmHg (0.13 glaucoma medications)
      to 11.9 +/- 4.1 mmHg (0.41 glaucoma medications). CONCLUSIONS: Conjunctival
      resurfacing with autologous tissue is an effective technique to repair late bleb
      leaks.

PMID- 10964830
TI  - Surgical repair of leaking filtering blebs

PMID- 10964829
TI  - Surgical repair of leaking filtering blebs.
AB  - PURPOSE: To report the surgical management of leaking filtering blebs occurring
      after blebitis or persistent hypotony. DESIGN: Retrospective, noncomparative case
      series. PARTICIPANTS: Twenty-two eyes of 20 patients with late bleb leak,
      blebitis or endophthalmitis, hypotony maculopathy, or bleb dysesthesia on
      presentation to the glaucoma service who required surgical bleb revision from
      1990 through 1999. INTERVENTION: Pedicle flap, partial excision, and advancement
      or free conjunctival autologous graft techniques for surgical bleb revision. Type
      of bleb revision was dependent on the dimensions of the bleb and quality of
      surrounding conjunctiva. MAIN OUTCOME MEASURES: Preoperative and postoperative
      intraocular pressure (IOP), status of bleb leak, reoperation for glaucoma, or
      requirement for postrevision glaucoma medical therapy, with success defined as
      the need for two or fewer glaucoma medications after revision. RESULTS: Eighty
      six percent (19/22) of eyes that underwent surgical bleb revision had resolution
      of leak and IOP control using two or fewer medications after one or more bleb
      revisions. The preoperative IOP (mean +/- standard deviation) was 3.7 +/- 2.6
      mmHg (range, 0-8 mmHg). After an average follow-up of 21 months (range, 8-108
      months), the IOP was 11.0 +/- 4.4 mmHg for patients taking 0.6 +/- 1.0 glaucoma
      medications. Eighteen percent (4/22) of eyes required two or more bleb revisions.
      In one eye, an IOP spike of 36 mmHg developed after revision, which required
      laser suture lysis on two occasions before the IOP was significantly lowered. The
      three failures were: one eye that required three or more medications for IOP
      control, a patient whose eye had a persistent leak after revision and who was not
      mentally competent to undergo repeat revision, and one eye that required combined
      glaucoma and cataract surgery after revision. CONCLUSIONS: Surgical bleb revision
      has a high success rate of closing late bleb leaks, maintaining glaucoma control,
      and preserving vision, with few postoperative complications. The appropriate
      surgical procedure for revision must be based on the individual clinical
      situation and can result in successful bleb revision.

PMID- 10964831
TI  - Visual field progression in patients with initially unilateral visual field loss
      from chronic open-angle glaucoma.
AB  - PURPOSE: To investigate visual field progression in patients with initially
      unilateral glaucomatous visual field loss, and to determine risk factors for
      progression. DESIGN: Retrospective observational case series. PARTICIPANTS: Forty
      eight consecutive patients with primary open-angle glaucoma, pseudoexfoliative
      glaucoma, or pigmentary glaucoma, seen over an 18-month period, who initially had
      unilateral visual field loss as defined by use of modified Anderson criteria.
      Patients were followed with standard Humphrey perimetry for a minimum of 2 years.
      METHODS: Progression was defined by use of modified Anderson criteria, and
      Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma
      Treatment Study scores. MAIN OUTCOME MEASURE: Visual field progression. RESULTS:
      Three patients (6.2%) had fellow eye progression over a mean follow-up of 76
      months and duration of disease of 8.7 years. Fellow eye progression correlated
      with progression of the first-affected eye (P = 0.044). Ten patients (21%) had
      progression of the first-affected eye; these eyes had a larger initial cup/disc
      ratio compared with stable eyes (P = 0.041). Increasing initial AGIS score was
      associated with progression (P: = 0.003). Kaplan-Meier survival analysis
      estimated the risk of progression at 5 years to be 25% in first-affected eyes and
      7.2% in fellow eyes. CONCLUSIONS: In this population, the risk of fellow eye
      progression in patients with initially unilateral visual field loss from open
      angle glaucoma is low. Progression is higher in eyes with visual field loss at
      initial testing, and the risk of progression increases as the level of initial
      visual field loss increases.

PMID- 10964832
TI  - Correlation between static automated and scanning laser entoptic perimetry in
      normal subjects and glaucoma patients.
AB  - OBJECTIVE: To compare the effectiveness of scanning laser entoptic perimetry with
      static automated perimetry as a noninvasive instrument for screening for
      glaucomatous damage in visually asymptomatic subjects within the central 60
      degrees (diameter) of vision. DESIGN: A masked cross-sectional study comparing
      entoptic perimetry to achromatic threshold perimetry. PARTICIPANTS: Twenty-three
      subjects and controls from the Sharp Rees-Stealy Hospital and the Shiley Eye
      Center at the University of California, San Diego. TESTING: Virtual reality-based
      entoptic perimetry was compared with achromatic threshold perimetry. MAIN OUTCOME
      MEASURES: For each testing session, we compared the presence of a disturbance in
      the entoptic perimetry stimulus with the presence of defects in visual function
      as measured by Humphrey automated visual field perimetry. RESULTS: Scanning laser
      entoptic perimetry reasonably estimates the overall visual field loss for
      moderate-to-severe scotomas as measured by the pattern deviation in standard
      visual field perimetry. Scanning laser entoptic perimetry has a sensitivity from
      27% to 90% and a specificity from 50% to 100% for screening moderate-to-severe
      visual field defects caused by glaucoma within the central 60 degrees diameter of
      vision. CONCLUSIONS: Scanning laser entoptic perimetry may be an effective and
      inexpensive screening test in hospitals and community clinics for diagnosing
      visual field loss caused by glaucoma.

PMID- 10964833
TI  - Open-angle glaucoma in an urban population in southern India: the Andhra Pradesh
      eye disease study.
AB  - OBJECTIVE: To assess the prevalence and features of open-angle glaucoma in an
      urban population in southern India. DESIGN: A population-based cross-sectional
      study. PARTICIPANTS: A total of 2522 persons (85.4% of those eligible) of all
      ages, including 1399 persons 30 years of age or older, from 24 clusters
      representative of the population of Hyderabad city. TESTING: The participants
      underwent an interview and detailed eye examination that included logarithm of
      minimum angle of resolution visual acuity, refraction, slit-lamp biomicroscopy,
      applanation tonometry, gonioscopy, dilatation, cataract grading, and stereoscopic
      fundus evaluation. Automated Humphrey threshold 24-2 visual fields (Humphrey
      Instruments Inc., San Leandro, CA) and optic disc photography were performed when
      indicated by standardized criteria for disc damage or if intraocular pressure
      (IOP) was 22 mmHg or more. MAIN OUTCOME MEASURES: Definite primary open-angle
      glaucoma (POAG) was defined as obvious glaucomatous optic disc damage and visual
      field loss in the presence of an open-angle, and suspected POAG was defined as
      suspected glaucomatous optic disc damage without definite visual field loss.
      Ocular hypertension (OHT) was defined as IOP of 22 mmHg or more without
      glaucomatous optic disc damage or visual field loss in the presence of an open
      angle. Glaucomatous optic disc damage or IOP of 22 mmHg or more secondary to an
      obvious cause and with an open-angle was defined as secondary open-angle
      glaucoma. RESULTS: Definite POAG, suspected POAG, and OHT were present in 27, 14,
      and 7 participants, respectively, with age- and gender-adjusted prevalence (95%
      confidence interval) of 1.62% (0.77%-2.48%), 0.79% (0.39%-1.41%), and 0.32%
      (0.10%-0.78%) in those 30 years of age or older, and 2.56% (1.22%-3.91%), 1.11%
      (0.43%-1.78%), and 0.42% (0.11%-1.12%) in those 40 years of age or older,
      respectively. The prevalence of POAG increased significantly with age using
      multivariate analysis (P < 0.001). Only two of 27 participants (7.4%) with
      definite POAG had been previously diagnosed and treated, and 66.7% of the
      previously undiagnosed had IOP less than 22 mmHg. Fourteen of 27 participants
      (51.9%) with definite POAG had severe glaucomatous damage based on optic disc and
      visual field criteria, of which five participants (18.5%) had at least one blind
      eye as a result of POAG (all with best-corrected distance visual acuity less than
      20/400 or central visual field less than 10 degrees); the other 13 participants
      (48.1%) had moderate glaucomatous damage. Because visual fields and optic disc
      photography were not performed on all participants, the prevalence of POAG may
      have been underestimated. Secondary open-angle glaucoma was present in one
      participant as a result of angle recession. CONCLUSIONS: The prevalence of open
      angle glaucoma in this urban population in southern India is at least as much as
      that reported recently from white populations in developed countries. However,
      the vast majority of persons with glaucoma were undiagnosed in this population,
      and a large proportion of those having definite POAG already had severe
      glaucomatous damage.

PMID- 10964834
TI  - Angle-closure glaucoma in an urban population in southern India. The Andhra
      Pradesh eye disease study.
AB  - OBJECTIVE: To assess the prevalence and features of angle-closure glaucoma (ACG)
      in an urban population in southern India. DESIGN: A population-based, cross
      sectional study. PARTICIPANTS: A total of 2522 (85.4% of those eligible) persons
      of all ages, including 1399 persons 30 years of age or older, from 24 clusters
      representative of the population of Hyderabad city. TESTING: The participants
      underwent an interview and detailed eye examination that included logarithm of
      minimum angle of resolution visual acuity, refraction, slit-lamp biomicroscopy,
      applanation tonometry, and gonioscopy; pupil dilatation and stereoscopic fundus
      evaluation was performed if the risk of angle-closure as a result of dilatation
      was not believed to be imminent. Humphrey threshold 24-2 visual fields (Humphrey
      Instruments Inc., San Leandro, CA) were performed when indicated by standardized
      criteria for disc damage or if intraocular pressure (IOP) was 22 mmHg or more.
      MAIN OUTCOME MEASURES: An occludable angle was defined as pigmented posterior
      trabecular meshwork not visible by gonioscopy in three quarters or more of the
      angle circumference. Manifest primary angle-closure glaucoma (PACG) was defined
      as IOP of 22 mmHg or more or glaucomatous optic disc damage with visual field
      loss in the presence of an occludable angle. An IOP of 22 mmHg or more or
      glaucomatous optic disc damage in the presence of an occludable angle secondary
      to an obvious cause was defined as secondary ACG. RESULTS: Manifest PACG and
      occludable angles without ACG were present in 12 and 24 participants,
      respectively, with age- and gender-adjusted prevalence (95% confidence interval
      [CI]) of 0.71% (0.34%-1.31%) and 1.41% (0.73%-2.09%) in participants 30 years of
      age or older, and 1.08% (0.36%-1.80%) and 2.21% (1.15%-3.27%) in participants 40
      years of age or older, respectively. With multivariate analysis, the prevalence
      of these two conditions considered together increased significantly with age (P <
      0.001); although not statistically significant, these were more common in females
      (odds ratio 1.70; 95% CI, 0.82-3.54) and in those belonging to lower
      socioeconomic strata as compared with middle and upper strata (odds ratio, 1.82;
      95% CI, 0.88-3.74). The odds of manifest PACG were higher in the presence of
      hyperopia of more than 2 diopters ([D]; odds ratio, 3.69; 95% CI, 0.89-15.2).
      Only four of 12 participants (33.3%) with manifest PACG had been previously
      diagnosed, and one of 12 (8.3%) had peripheral iridotomy performed previously.
      Manifest PACG had caused blindness in one or both eyes in five of these 12
      participants (41.7%); best-corrected distance visual acuity less than 20/400 in
      one or both eyes in four patients, and acuity less than 20/200 in one eye in
      another patient. Most (83.3%) of those with manifest PACG could be classified as
      having chronic form of the disease. We may have underestimated manifest PACG
      because visual fields were per- formed only on those with clinical suspicion of
      optic disc damage. Secondary ACG was present in two participants. CONCLUSIONS:
      The prevalence of PACG in this urban population in southern India is close to
      that reported recently in a Mongolian population. A large proportion of the PACG
      in this population was undiagnosed and untreated. Because visual loss resulting
      from PACG is potentially preventable if peripheral iridotomy or iridectomy is
      performed in the early stage, strategies for early detection of PACG could reduce
      the high risk of blindness resulting from PACG seen in this urban population in
      India.

PMID- 10964836
TI  - Subretinal fibrosis in patients with Vogt-Koyanagi-Harada disease.
AB  - OBJECTIVE: To describe subretinal fibrosis as a long-term complication of Vogt
      Koyanagi-Harada (VKH) disease. DESIGN: Retrospective, clinic-based, cross
      sectional study and clinical correlation. PARTICIPANTS: Ten patients with VKH
      disease and subretinal fibrosis were seen at two uveitis referral centers between
      1977 and 1997. INTERVENTION: A review of the historical, clinical, and
      fluorescein angiographic features was performed. MAIN OUTCOME MEASURES: The
      prevalence, demographic and clinical features, and time to development of
      subretinal fibrosis were summarized. RESULTS: Subretinal fibrosis occurred in 20
      eyes of 10 patients with VKH disease, an overall prevalence of 8% between the two
      institutions. Patient age ranged from 16 years to 48 years, with a median of 34.5
      years. Five patients were Hispanic, one was mixed Hispanic and American Indian,
      three were Asian or mixed Asian and Caucasian, and one was African-American.
      Eight of the 10 patients were men. All patients were in the chronic, recurrent
      phase of their disease when they had subretinal fibrosis develop, and all
      patients had recurrent episodes of posterior uveitis. Presenting vision ranged
      from 20/20 to light perception, with a median acuity of 20/200. All patients were
      initially treated with oral and topical corticosteroids. Four patients required
      additional noncorticosteroid immunosuppressive therapy. Time from diagnosis of
      VKH disease to development of subretinal fibrosis ranged from zero (fibrosis
      present at time of diagnosis) to 27 years, with a median time of 10 months. The
      median time from diagnosis of VKH to development of subretinal fibrosis in
      Hispanic patients was 6.5 months, whereas in non-Hispanic patients it was 6.5
      years. Final vision ranged from 20/25 to light perception, with a median acuity
      of 20/60. Seven of 20 eyes had a final visual acuity of 20/40 or better, and
      seven eyes saw 20/200 or worse. Five of the eyes with 20/200 or worse vision had
      fibrosis involving the fovea. CONCLUSIONS: Subretinal fibrosis occurs in a
      sizeable proportion of patients with VKH disease and may contribute to permanent
      loss of vision.

PMID- 10964835
TI  - The role of angiotensin converting enzyme and angiotensin II type 1 receptor gene
      polymorphisms in patients with nonarteritic anterior ischemic optic neuropathy.
AB  - OBJECTIVE: To determine the role of angiotensin converting enzyme (ACE) and
      angiotensin II type 1 receptor (AT1R) polymorphisms in the pathogenesis of
      nonartertic anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective,
      case-control study. PARTICIPANTS: Seventy-four patients with NAION diagnosed from
      1984 through 1999. Seventy-one patients who visited the Eye Institute comprised
      the control group. TESTING INTERVENTION: DNA was extracted from whole blood
      obtained from all patients and control participants. Polymerase chain reaction
      (PCR) was used for analysis of ACE and AT1R polymorphisms. RESULTS: The frequency
      of the polymorphism for ACE among the NAION patients (39.2% deletion allele [DD],
      54.0% deletion/insertion [D/I] locus, 6.8% insertion allele [II]) was similar to
      that of the control group (50.7% DD, 39.4% D/I, 9.9% II), with P = 0.21. The
      frequency of the polymorphism of AT1R in the NAION patients was 5.4% CC, 44.6%
      CA, 50% AA, and in the control group it was 4.2% CC, 33.8% CA, 62.0% AA, with P =
      0.35. Participants less than 55 years of age and those more than 55 had quite
      similar distributions. CONCLUSIONS: Angiotensin converting enzyme and AT1R
      polymorphisms have no part in the mechanism of NAION. Thus drugs such as ACE
      inhibitors or AT1R antagonists are not specifically indicated for treatment of
      these patients.

PMID- 10964837
TI  - Ultrasound biomicroscopy of sclerotomy sites after pars plana vitrectomy for
      diabetic vitreous hemorrhage.
AB  - OBJECTIVE: This study was aimed at assessing changes at the sclerotomy site using
      the ultrasound biomicroscope (UBM) in eyes that underwent primary pars plana
      vitrectomy for complications of proliferative diabetic retinopathy. DESIGN:
      Prospective, observational case series. PARTICIPANTS: Eighty-six eyes of 84
      patients with vitreous hemorrhage caused by proliferative diabetic retinopathy.
      INTERVENTION: Three-port pars plana vitrectomy followed by UBM evaluation of all
      sclerotomy sites between 6 and 8 weeks after surgery. Correlation with
      intraoperative findings done in case of reoperations. Forty-one eyes had repeat
      UBM at 6 months. MAIN OUTCOME MEASURES: The changes at the sclerotomy site were
      classified into six groups: well healed, gape, plaque, vitreous incarceration,
      fibrovascular proliferation, and anterior hyaloidal fibrovascular proliferation
      (AHFVP). The UBM characteristics of each of the groups were defined. The findings
      at 6 months were compared with those at 6 to 8 weeks. RESULTS: At 6 to 8 weeks
      after surgery, most sclerotomies were well healed or had either moderate to high
      reflective plaques bridging the site. Wound gape was seen in 22.1% of active
      ports, 32.6% of light ports, and 25.6% of infusion ports. Vitreous incarceration
      was seen most often at the infusion port (18. 6% of eyes). Fibrovascular
      proliferation was seen in 9.3% of active ports, 12.8% of light ports, and 15.1%
      of infusion ports. Thirteen eyes had recurrent vitreous hemorrhage 6 to 8 weeks
      after surgery. Cases with rebleeding and no fibrovascular proliferation at the
      sclerotomy on UBM did well with outpatient fluid-air exchange (two eyes) or
      observation only (three eyes). Those with fibrovascular proliferation on UBM
      (eight eyes) required more extensive surgery. CONCLUSIONS: UBM is helpful in
      detecting complications at the sclerotomy sites after pars plana vitrectomy and
      is an invaluable tool in the assessment of the patient before reoperation.

PMID- 10964838
TI  - Ophthalmologic findings in Cohen syndrome. A long-term follow-up.
AB  - OBJECTIVE: To determine the nature and course of ophthalmologic abnormalities and
      their clinical significance in Cohen syndrome. STUDY DESIGN: Observational case
      series. PARTICIPANTS: Twenty-two Cohen syndrome patients aged 2 to 57 years were
      examined, and a retrospective review of ophthalmologic records was carried out
      for 14 of them. All but one were part of the Finnish study of refined mapping of
      the Cohen syndrome gene by linkage disequilibrium in chromosome 8. MAIN OUTCOME
      MEASURES: Visual acuity (VA), cycloplegic refraction, biomicroscopy, lens
      opacitometry, ophthalmoscopy, and fundus photography. RESULTS: With the exception
      of the two youngest patients, all had symptoms such as nyctalopia, impaired
      vision, and visual field loss. Progressive, often high-grade myopia, astigmatism,
      and retinochoroidal dystrophy resembling retinitis pigmentosa occurred in all,
      except for the youngest patients. The earliest fundus changes were pale disc and
      pale fundus with or without pigment granularity, followed by narrowed vessels,
      pigment clumps, and bone spiculelike pigment accumulations by 10 to 20 years of
      age. Pigment deposits increased and approached the posterior pole by 35 to 40
      years of age. Patients more than 45 years of age had severe retinochoroidal
      atrophy. A bull's-eye macula was seen in most patients. Teenagers had peripheral
      lens opacities, and young adults had early nuclear sclerosis confirmed by lens
      opacitometry. Older patients also had posterior subcapsular cataracts, iris
      atrophy, and iridophacodonesis. Vision started to deteriorate at the age of 6 to
      10 years, but remained relatively good (VA 0.5-0.1) in most patients until 30
      and, in one case, 46 years of age. Older patients were severely visually
      handicapped (VA hand motion to light perception), but none were completely blind.
      CONCLUSIONS: Progressive myopia and retinochoroidal dystrophy are essential
      features in Cohen syndrome and, together with early lens opacities, lead to
      deterioration of vision. Cohen syndrome patients need careful ophthalmologic
      follow-up at all ages. Nyctalopia and restricted visual fields should be
      considered when planning the patient's daily activities.

PMID- 10964839
TI  - Histopathologic and immunocytochemical analysis of the retina and ocular tissues
      in Batten disease.
AB  - PURPOSE: To describe the pathophysiologic features of retinal degeneration in
      Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) caused by
      mutations in the CLN3 gene. STUDY DESIGN: Comparative human tissue study.
      MATERIALS: The retina and other ocular tissues of a 22-year-old man with JNCL
      were compared with the same tissues of a healthy 30-year-old man. DNA from whole
      blood and RNA from retina were used for genotype analysis. METHODS: The retinas,
      corneas, conjunctiva, and ciliary body were processed for histopathologic and
      immunofluorescence analysis. Genomic DNA was subjected to polymerase chain
      reaction (PCR) and nucleotide sequence analyses. Reverse transcriptase/PCR and
      sequence analysis were performed on retinal RNA. RESULTS: The JNCL donor was
      heterozygous for a approximately 1 kb deletion in CLN3, as found in most JNCL
      patients. The other allele had a single base pair deletion in exon 6 that
      resulted in a frame shift. Gross pathology of the JNCL retina resembled that in
      retinitis pigmentosa, including deposits of bone spicule pigment. Histopathologic
      studies revealed loss of neurons from all retinal layers. Immunofluorescence
      labeling with antibodies to rhodopsin, recoverin, and cone opsin demonstrated
      degenerate rods and cones with short outer segments in the far periphery.
      Autofluorescent lipopigment granules were prominent in ganglion cells and some
      cells of the inner nuclear layer, but not in the photoreceptors. The retinal
      pigment epithelium (RPE) had fewer lipofuscin granules than the control specimen.
      Increased numbers of lipofuscin granules were found in the epithelia of the
      ciliary body and conjunctiva, but not in the cornea of the JNCL eye. CONCLUSIONS:
      Immunofluorescence studies revealed degenerate rods and cones in the far
      periphery. Lipofuscin granules were decreased in the RPE, consistent with loss of
      photoreceptor outer segments. The novel finding that degenerate photoreceptors
      did not contain autofluorescent inclusions suggests that granule accumulation may
      not precede photoreceptor degeneration in JNCL. The presence of normal
      photoreceptor proteins in the degenerate rods and cones suggests that these cells
      may be capable of functional regeneration if a therapy for Batten disease is
      developed.

PMID- 10964840
TI  - The effects of experimental tear film removal on corneal surface regularity and
      barrier function.
AB  - PURPOSE: To evaluate corneal surface regularity and asymmetry, corneal thickness,
      barrier function, and contrast sensitivity after experimental removal of the
      precorneal tear layer. DESIGN: Prospective, clinic-based, nonrandomized (self
      controlled) comparative trial. PARTICIPANTS: Six eyes of six healthy volunteers
      (three males, three females; age range, 29-40 years). METHODS: A precorneal tear
      lesion was created by pressing a sterile Biopore (Millipore, Bedford, MA) Teflon
      membrane against the central cornea. Corneal topography with both the Topographic
      Modeling System (TMS-1; Computed Anatomy, Tomey Technology, Cambridge, MA) and
      the Orbscan (Orbscan Inc., Salt Lake City, UT) were performed before the lesion
      was created and 30 seconds, 1 hour, and 4 hours after the lesion was created.
      Surface regularity and surface asymmetry indices were evaluated by the TMS-1
      topography system. Maximum and minimum keratometric readings, corneal fluorescein
      staining, contrast sensitivity, and corneal thickness were evaluated before and
      after the tear lesion. Cytologic membranes were stained for MUC4 mucin using an
      indirect immunofluorescent staining technique. Confocal microscopy was performed
      to evaluate the integrity of the corneal epithelium in two eyes. Analysis of
      variance with polynomial contrasts was used to examine time trends of the outcome
      variables. MAIN OUTCOME MEASURES: The change in corneal surface regularity and
      asymmetry indices, corneal thickness, permeability to fluorescein dye, and
      contrast sensitivity before and after the lesion was made were compared. RESULTS:
      The corneal epithelium in the area of the lesion showed intense fluorescein
      staining 30 seconds postlesion but appeared normal by 4 hours. Confluent,
      homogeneous staining for MUC4 mucin was observed on the membranes used to create
      the lesion in all cases. The surface regularity index measured with the TMS-1
      increased after the lesion was created and decreased toward normal by 4 hours (P
      = 0.017). Corneal thickness measured by the Orbscan instrument significantly
      increased in the central (P = 0.001), superior (P = 0.006), inferotemporal (P <
      0.001) and superotemporal (P = 0.001) cornea immediately following the lesion and
      returned to normal by 4 hours. The lesion caused a decrease in visual acuity at
      6.30%, 4% and 2.5% contrast sensitivities 1 hour postlesion and these
      measurements returned to prelesion values by 4 hours (P = 0.085, P = 0.005, P =
      0.043). CONCLUSIONS: The precorneal tear layer serves as a permeability barrier
      and is essential for maintaining a smooth quality optical surface.

PMID- 10964841
TI  - Band-shaped and whorled microcystic dystrophy of the corneal epithelium.
AB  - OBJECTIVE: To report the clinical, histopathologic, and electron microscopic
      features of band-shaped and whorled microcystic corneal epithelial dystrophy.
      DESIGN: Two interventional case reports. PARTICIPANTS: Two patients, two eyes.
      INTERVENTION: The involved area of corneal epithelium was scraped from each
      cornea. RESULTS: Histopathologic examination showed microscopic vacuoles in the
      epithelial cytoplasm in both cases. Electron microscopic examination revealed
      mainly empty cytoplasmic vacuoles with scant nonspecific osmophilic material. The
      process recurred clinically in one patient. Changes in corneal topography are
      documented in one patient. CONCLUSION: Clinical findings and pathologic studies
      seem nearly identical to those in the original report. No pattern of systemic
      disorder or medication use was found. The cause of this condition remains
      unknown.

PMID- 10964842
TI  - Large-diameter lamellar keratoplasty in severe ocular alkali burns: A technique
      of stem cell transplantation.
AB  - PURPOSE: To evaluate the efficacy of large-diameter lamellar keratoplasty in
      cases of severe ocular alkali burns. DESIGN: Prospective, noncomparative,
      interventional case series. PARTICIPANTS: Nine eyes of nine patients with severe
      ocular alkali burns (grade III/IV) exhibiting corneal vascularization,
      conjunctivalization, and chronic inflammation were recruited from the Cornea
      Clinic of Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, a
      tertiary eye care center. INTERVENTION: Large-diameter lamellar keratoplasty was
      performed using McCarey-Kaufman media-preserved donor corneas. The patients were
      followed up for a minimum of 6 months. MAIN OUTCOME MEASURES: Symptomatic relief,
      time to epithelialization, best-corrected visual acuity, Schirmer I, tear film
      break-up time, and central corneal clarity were the parameters evaluated.
      RESULTS: The mean duration between the injury and surgery was 29.5 +/- 19.4
      months. No intraoperative complications were seen. Successful epithelialization
      of the ocular surface was achieved in all but one eye, and the mean time to
      epithelialization was 5.2 +/- 4.9 days. One eye had a persistent epithelial
      defect which was managed with a bandage soft contact lens. All patients achieved
      symptomatic relief. The preoperative best-corrected visual acuity was </=1/60 in
      all the patients. There was a significant improvement in vision in six eyes
      postoperatively (P = 0.013). The corneal clarity was grade 2+ or better in five
      eyes and 1+ in four eyes. No recurrence of corneal vascularization or signs of
      rejection were seen in any eye during the mean follow-up of 7.4 +/- 3.2 months.
      Causes of no improvement of vision included the presence of subepithelial
      nebulomacular haze in one eye caused by persistent epithelial defect and residual
      stromal haze. CONCLUSIONS: Large-diameter lamellar keratoplasty is a useful
      therapeutic modality in cases of severe alkali burns. It is a single-stage
      procedure that provides a stable ocular surface because of stem cell
      supplementation and may visually rehabilitate the patient.

PMID- 10964843
TI  - Corneal microsporidiosis. Report of case, including electron microscopic
      observations.
AB  - OBJECTIVE: To report a case of corneal stromal infection caused by a protozoon of
      the genus MICROSPORIDIA:, including clinical, histopathologic, and electron
      microscopic observations. DESIGN: Case report. METHODS: Light and electron
      microscopy studies were performed on keratectomy specimens from a 67-year-old
      immunocompetent man who had a unilateral chronic stromal keratitis that was
      refractory to medical treatment. Initial corneal biopsy followed by lamellar and
      penetrating keratoplasty were performed on the patient. All the specimens were
      studied histopathologically. RESULTS: Light microscopy of the corneal biopsy and
      the subsequent keratectomy specimens demonstrated myriad small, round to oval
      microsporidial organisms measuring 3.5 to 5.0 micrometer in length that stained
      positively with the periodic acid-Schiff, Grocott-methenamine silver, and acid
      fast methods and were gram positive. Electron microscopic observations
      demonstrated viable blastospores that had a thin osmiophilic outer cell wall and
      contained 11 to 13 coils of the filament. The light and electron microscopic
      features, the tinctorial characteristics, and the selective corneal stromal
      involvement are consistent with microsporidial keratitis. CONCLUSIONS:
      Microsporidiosis should be considered in the differential diagnosis of a culture
      negative stromal keratitis refractory to medical treatment. The diagnosis can be
      easily established based on the morphologic features of the protozoa in the
      keratectomy specimens. No effective medical treatment for the stromal disease is
      available. Full-thickness keratoplasty is suggested because, in our patient,
      lamellar keratoplasty did not preclude recurrence of the disease.

PMID- 10964845
TI  - Toric intraocular lenses for correcting astigmatism in 130 eyes

PMID- 10964844
TI  - Toric intraocular lenses for correcting astigmatism in 130 eyes.
AB  - OBJECTIVE: This study evaluated the results after implantation of toric
      intraocular lenses (IOLs) to correct preexisting corneal astigmatism in patients
      undergoing either cataract or clear lens extraction surgery. DESIGN:
      Retrospective, noncomparative case series. PARTICIPANTS: One hundred thirty eyes
      of 99 patients who underwent phacoemulsification and posterior chamber toric IOL
      implantation from January 1997 through February 1998 were included in the study.
      INTERVENTION: Implantation of a toric IOL was performed after cataract surgery
      (122 eyes) or clear lens extraction surgery (eight eyes). Both preoperative
      corneal cylinder and refractive cylinder powers were more than 1.50 diopters (D)
      for all the eyes included in this study. To provide a comparison, we also studied
      51 eyes of 45 patients meeting the same preoperative criteria for degree of
      corneal and refractive cylinder who underwent implantation of a spherical
      (nontoric) IOL combined with limbal relaxing incisions. The data for both study
      and comparison groups were analyzed retrospectively. The selection for the two
      groups was arbitrary. MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA),
      mean spherical equivalent, residual refractive cylinder, and toric IOL axis.
      RESULTS: In the toric IOL group, 84% of eyes achieved 20/40 or better UCVA. In
      the spherical IOL group, 76% achieved 20/40 or better UCVA. The mean
      postoperative refractive cylinder was -1.03 +/- 0.79 D in the toric IOL group and
      -1.49 +/- 0.75 D in the spherical IOL group. CONCLUSIONS: Our results indicate
      that phacoemulsification and posterior chamber toric IOL implantation is a
      largely predictable new surgical option to correct preexisting corneal
      astigmatism in cataract or clear lens extraction surgery.

PMID- 10964846
TI  - Functional outcome and satisfaction after photorefractive keratectomy. Part 1:
      development and validation of a survey questionnaire.
AB  - OBJECTIVE: The aim of this study was to develop a valid, reliable, and easy-to
      administer instrument to assess patient satisfaction and perceived outcome after
      bilateral excimer laser photorefractive keratectomy. DESIGN: Development and
      validation of a psychometric questionnaire. PARTICIPANTS: Consecutive patients
      who underwent bilateral excimer laser photorefractive keratectomy from May 1994
      through May 1997 by 12 surgeons from four collaborating centers. To be eligible,
      a minimum of 4 months since the last surgery and a maximum of 30 months since the
      first surgery was required. METHODS: The new instrument was derived in part from
      the Prospective Evaluation of Radial Keratotomy (PERK) study 10-year psychometric
      questionnaire and the Visual Functional Index (VF-14), an index of functional
      impairment in patients with cataract. Questions were grouped in seven scales,
      each covering a specific aspect of quality of vision. These included global
      satisfaction, quality of uncorrected vision, quality of corrected vision, quality
      of night vision, glare, daytime driving, and night driving. MAIN OUTCOME
      MEASURES: Acceptability, reliability, validity, and interpretability of the
      instrument, as well as its ease of administration. RESULTS: The instrument scale
      structure was examined and scale scores were created. Item-discriminant validity
      ensured that questions belonged to their hypothesized scale, based on multitrait
      correlation analysis. The instrument was shown to be reliable by a high level of
      internal consistency, and all Cronbach's alpha coefficients were superior or
      equal to 0.83. Construct-related validity and interpretability were assessed
      based on correlations between scale scores and clinically recognized success
      criteria such as visual acuity and refraction. Respondent burden was shown to be
      minimal. Acceptability of the instrument was shown to be very good, with a
      participation rate of 74.3% (690 of 929 patients). The instrument is available in
      English and in French and the translation was shown to be reliable. CONCLUSIONS:
      The acceptability, reliability, and interpretability of the instrument, as well
      as its ease of administration, were shown to be adequate. This questionnaire
      appears clinically useful to document patient satisfaction after excimer laser
      photorefractive keratectomy.

PMID- 10964847
TI  - Functional outcome and satisfaction after photorefractive keratectomy. Part 2:
      survey of 690 patients.
AB  - PURPOSE: To document patient satisfaction and self-perceived quality of vision
      after bilateral photorefractive keratectomy (PRK). DESIGN: Noncomparative,
      interventional case series. PARTICIPANTS: Consecutive patients who underwent
      bilateral PRK from May 1994 through May 1997 by the 12 surgeons of four
      collaborating centers with a minimum of 4 months since the last surgery and up to
      30 months since the first surgery. METHODS: A questionnaire with known
      psychometric properties was self-administered by the patients. MAIN OUTCOME
      MEASURES: Responses to individual questions and scale scores. RESULTS: A total of
      929 questionnaires were sent, of which 690 were answered and returned (74.3%
      response rate). The preoperative spherical equivalent ranged from -0.38 diopters
      [D] to -27.75 D (mean, -5.32 D; standard deviation, 2.85 D). Although 91.8% of
      the patients were satisfied or very satisfied with their surgery, 96.3%
      considered that their main goal had been reached, and 95.7% would still choose to
      have surgery if they had it to do over. The degree of satisfaction was
      proportional to the postoperative uncorrected visual acuity in the best eye
      expressed in LogMAR (r = -0.18, P: = 0. 0001) and was negatively correlated with
      the importance of the corneal haze (r = -0.23, P = 0.0001). Daytime glare was
      reported to be greater than before surgery by 55.1% of patients. A decrease in
      night vision was reported by 31.7% of patients, and 31.1% of patients reported
      increased difficulty driving at night because of their vision. CONCLUSIONS:
      Overall satisfaction after PRK for low to severe myopia appears to be very good.
      Glare and night vision disturbance, particularly bothersome for night driving,
      seem to constitute significant secondary effects that deserve further
      investigation and should be kept in mind for future improvements in the
      technique.

PMID- 10964849
TI  - Repairing the bond in important relationships: a dynamic for personality
      maturation.
AB  - OBJECTIVE: The author sought to establish a common set of interactional dynamics
      involved in growth-facilitating interpersonal relationships. METHOD: Empirical
      studies of the three most common dyadic relationships associated with personality
      growth were reviewed: infant-mother attachment behaviors, the psychotherapeutic
      alliance, and the marital relationship. RESULTS: Empirical and clinical studies
      support the conclusion that growth is facilitated when a strong affective bond is
      established with an important other and the inevitable disruptions of this bond
      are repaired. CONCLUSIONS: Personality maturation across the lifespan has been
      attributed to the internalization of admirable qualities of important others. The
      data surveyed suggest that the interactional dynamics associated with
      internalization involve establishing a strong affective bond with an important
      other and repairing this bond's inevitable ruptures. It is both the rupture and
      the repair that are crucial.

PMID- 10964850
TI  - Depression in schizophrenia: perspective in the era of "Atypical" antipsychotic
      agents.
AB  - OBJECTIVE: The author sought to provide a contemporary understanding of
      depression in schizophrenia and promote a treatment orientation. METHOD: Computer
      and library-based resources were used to review the literature on depression in
      schizophrenia. RESULTS: Despite multiple definitions of "depression," a
      substantial rate of depression has consistently been found in patients with
      schizophrenia. A differential diagnosis can be used to advance the understanding
      and treatment of depression in schizophrenia, and changes in response to the
      advent of atypical antipsychotic agents can be understood in the context of this
      differential diagnosis paradigm. CONCLUSIONS: Depression is an important co
      occurring syndrome in schizophrenia. In at least some schizophrenic patients, the
      stress-vulnerability model has potential as an integrating concept concerning the
      relationship between depression and psychosis.

PMID- 10964852
TI  - A homeless person with bipolar disorder and a history of serious self-mutilation.

PMID- 10964853
TI  - The token economy.

PMID- 10964854
TI  - Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's
      disease at follow-up.
AB  - OBJECTIVE: This study evaluated the predictive utility of olfactory
      identification deficits in patients with mild cognitive impairment for follow-up
      diagnosis of probable Alzheimer's disease. METHOD: Ninety outpatients with mild
      cognitive impairment were examined at 6-month intervals. Matched healthy
      comparison subjects (N=45) were examined annually. The University of Pennsylvania
      Smell Identification Test was given at baseline. RESULTS: Olfaction scores were
      lower in patients with mild cognitive impairment than in healthy comparison
      subjects. Seventy-seven patients were followed up; 19 were diagnosed with
      Alzheimer's disease by 2 years. Patients with low olfaction scores (< or =34 of
      40), and patients with low olfaction scores who reported no subjective problems
      smelling, were more likely to develop Alzheimer's disease than other patients. In
      a Cox proportional hazards model adjusted for age, sex, modified Mini-Mental
      State score, and education, low olfaction scores did not predict time until
      development of Alzheimer's disease, but low olfaction scores accompanied by lack
      of awareness of olfactory deficits predicted time to development of Alzheimer's
      disease. This effect remained when attention or memory measures replaced modified
      Mini-Mental State score in the model. In patients with high Mini-Mental State
      scores (> or =27 of 30), low olfaction with lack of awareness remained a
      significant predictor of Alzheimer's disease. Olfaction scores of 30-35 showed
      moderate to strong sensitivity and specificity for diagnosis of Alzheimer's
      disease at follow-up. CONCLUSIONS: In patients with mild cognitive impairment,
      olfactory identification deficits, particularly with lack of awareness of
      olfactory deficits, may have clinical utility as an early diagnostic marker for
      Alzheimer's disease.

PMID- 10964855
TI  - Adolescent personality disorders associated with violence and criminal behavior
      during adolescence and early adulthood.
AB  - OBJECTIVE: A community-based, longitudinal prospective study was conducted to
      investigate whether personality disorders during adolescence are associated with
      elevated risk for violent behavior during adolescence and early adulthood.
      METHOD: A community-based sample of 717 youths from upstate New York and their
      mothers were interviewed in 1983, 1985-1986, and 1991-1993. Axis I and II
      disorders were assessed in 1983 and 1985-1986. Antisocial personality disorder
      was not assessed because most participants were less than 18 years of age in 1983
      and 1985-1986. Violent behavior was assessed in 1985-1986 and 1991-1993. RESULTS:
      Adolescents with a greater number of DSM-IV cluster A or cluster B personality
      disorder symptoms were more likely than other adolescents in the community to
      commit violent acts during adolescence and early adulthood, including arson,
      assault, breaking and entering, initiating physical fights, robbery, and threats
      to injure others. These associations remained significant after controlling for
      the youths' age and sex, for parental psychopathology and socioeconomic status,
      and for co-occurring psychiatric disorders during adolescence. Paranoid,
      narcissistic, and passive-aggressive personality disorder symptoms during
      adolescence were independently associated with risk for violent acts and criminal
      behavior during adolescence and early adulthood after the covariates were
      controlled. CONCLUSIONS: Cluster A and cluster B personality disorders and
      paranoid, narcissistic, and passive-aggressive personality disorder symptoms
      during adolescence may increase risk for violent behavior that persists into
      early adulthood.

PMID- 10964856
TI  - Impact of sexual abuse on the HIV-risk-related behavior of adolescents in
      intensive psychiatric treatment.
AB  - OBJECTIVE: This study compared the HIV-risk-related behaviors and attitudes of
      adolescents with and without a history of sexual abuse who were in intensive
      psychiatric treatment. METHOD: Adolescent patients (N=208) completed measures of
      psychological functioning and HIV-related knowledge, attitudes, and behaviors.
      RESULTS: Among sexually active adolescents in psychiatric treatment (N=116),
      those with a history of abuse reported significantly less condom self-efficacy
      (emotional ability to use condoms), less knowledge of HIV, less impulse control,
      less frequent use and purchase of condoms, and significantly higher rates of
      sexually transmitted diseases than their peers. Multiple logistic regression
      indicated that a history of sexual abuse was strongly associated with
      inconsistent condom use. CONCLUSIONS: Sexual abuse was associated with HIV-risk
      related attitudes and behaviors among adolescents in psychiatric treatment.
      Clinicians should thus view a history of sexual abuse as a marker for sexual
      behavior that puts adolescents at risk for HIV.

PMID- 10964857
TI  - Attention, memory, and motor skills as childhood predictors of schizophrenia
      related psychoses: the New York High-Risk Project.
AB  - OBJECTIVE: Childhood neurobehavioral deficits in offspring of schizophrenic,
      affectively ill, and psychiatrically normal parents were evaluated as predictors
      of schizophrenia-related psychoses in adulthood. METHOD: The offspring were
      tested with neurobehavioral measures at 7-12 years of age and assessed in mid
      adulthood for axis I diagnoses. The relationships of childhood deficits in
      attention, verbal memory, and gross motor skills to adulthood schizophrenia
      related psychoses were examined in separate path analyses by using logistic
      regression equations. Sensitivity and specificity were determined for each of the
      childhood dysfunctions. RESULTS: For the offspring of schizophrenic parents,
      childhood deficits in verbal memory, gross motor skills, and attention identified
      83%, 75%, and 58%, respectively, of the subjects with schizophrenia-related
      psychoses; 50% were identified by all three variables combined. False positive
      rates in subjects who did not develop schizophrenia-related psychoses ranged from
      18% for those with deficits in attention during childhood to 28% for those with
      deficits in memory. The three variables had low deficit rates in the offspring of
      the other two parental groups and were not associated with other psychiatric
      disorders in any group. CONCLUSIONS: Schizophrenia-related psychoses in adulthood
      are distinguished in subjects at risk for schizophrenia by childhood deficits in
      verbal memory, gross motor skills, and attention. The findings suggest that
      deficits in these variables are relatively specific to schizophrenia risk and may
      be indicators of the genetic liability to schizophrenia.

PMID- 10964858
TI  - Timing of onset of antidepressant response with fluoxetine treatment.
AB  - OBJECTIVE: The purpose of this study was to assess the time until onset of
      antidepressant response with fluoxetine treatment. METHOD: The authors evaluated
      182 outpatients with major depression who had a sustained acute response to
      fluoxetine treatment. The outpatients received 8 weeks of treatment with 20
      mg/day of fluoxetine and were assessed biweekly with the 17-item Hamilton
      Depression Rating Scale. The onset of response was defined as a 30% decrease in
      score on the Hamilton depression scale that persisted and led to a 50% decrease
      by week 8. The Kaplan-Meier product limit and Cox regression analysis were used
      to model the relationship between relevant variables and time until onset of
      response. RESULTS: The authors found that at weeks 2, 4, and 6, the probabilities
      of having an onset of response (for responders) were 55.5%, 24.7%, and 9.3%,
      respectively. The cumulative probabilities of onset of response at each time
      point were 55.5%, 80.2%, and 89.5%. Neither demographics nor clinical
      characteristics of depression predicted time until initial response. CONCLUSIONS:
      These data suggest that more than half of eventual responders to fluoxetine
      treatment at 8 weeks start to respond by week 2; over 75% start to respond by
      week 4. Conversely, the lack of onset of response at 4-6 weeks was associated
      with about a 73%-88% chance that patients would not have an onset of response by
      8 weeks.

PMID- 10964859
TI  - Double-blind, placebo-controlled trial of the use of lithium to augment
      antidepressant medication in continuation treatment of unipolar major depression.
AB  - OBJECTIVE: Use of lithium to augment antidepressant medication has been shown to
      be beneficial in the acute treatment of depression. The authors examined the
      efficacy of lithium augmentation in the continuation treatment of unipolar major
      depressive disorder. METHOD: Thirty patients with a refractory major depressive
      episode who had responded to acute lithium augmentation during an open 6-week
      study participated in a randomized, parallel-group, double-blind, placebo
      controlled trial of lithium augmentation during continuation treatment. After a 2
      4-week stabilization period following remission, patients were randomly assigned
      to receive either lithium or placebo for a 4-month period. Antidepressant
      medication was continued throughout the study. RESULTS: Relapses (including one
      suicide) occurred in seven (47%) of the 15 patients who received placebo in
      addition to antidepressants. None (0%) of the 14 patients who received lithium
      augmentation with antidepressants suffered a relapse during the double-blind
      phase of the study. Five of the seven relapsing patients in the placebo group
      developed a depressive episode, and the other two experienced a manic episode.
      CONCLUSIONS: Lithium augmentation in the continuation phase of treatment of
      unipolar major depressive disorder effectively protects patients against a
      relapse. Patients who respond to lithium augmentation should be maintained on
      lithium augmentation for a minimum of 6 months or even longer.

PMID- 10964860
TI  - Double-blind comparison of sertraline, imipramine, and placebo in the treatment
      of dysthymia: effects on personality.
AB  - OBJECTIVE: Although previous studies have shown that dysthymia, or chronic
      depression, commonly responds to antidepressant medications (with improvements in
      depressive symptoms and psychosocial functioning), there have been no systematic
      studies of the impact of antidepressant treatment on personality variables in
      patients with this disorder. METHOD: In a multicenter study, 410 patients with
      early-onset primary dysthymia were treated in a randomized prospective fashion
      with sertraline, imipramine, or placebo. The data were analyzed in terms of the
      subjects' scores on the Tridimensional Personality Questionnaire, a 100-item self
      report instrument that measures four temperamental dimensions: harm avoidance,
      reward dependence, novelty seeking, and persistence. RESULTS: At baseline, the
      harm avoidance scores of the dysthymic subjects were approximately 1.5 standard
      deviations higher than those of a previously reported community sample. After
      treatment, there was a significant decrease in harm avoidance scores, with no
      significant between-group differences. Remission of dysthymia was associated with
      significantly greater improvement in harm avoidance, with the greatest numerical
      change found in the patients treated with sertraline. Subjects' Tridimensional
      Personality Questionnaire scores were correlated at a 0.50 level with the Social
      Adjustment Scale both pre- and posttreatment, suggesting that a high degree of
      harm avoidance may be associated with poor social functioning. CONCLUSIONS:
      Before treatment, chronically depressed patients demonstrate an abnormality in
      temperament, as measured by elevated degrees of harm avoidance. Remission of
      dysthymia is associated with improvement in this aspect of temperament.

PMID- 10964861
TI  - Gender differences in treatment response to sertraline versus imipramine in
      chronic depression.
AB  - OBJECTIVE: The authors examined gender differences in treatment response to
      sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a
      tricyclic antidepressant, in chronic depression. METHOD: A total of 235 male and
      400 female outpatients with DSM-III-R chronic major depression or double
      depression (i.e., major depression superimposed on dysthymia) were randomly
      assigned to 12 weeks of double-blind treatment with sertraline or with imipramine
      after placebo washout. RESULTS: Women were significantly more likely to show a
      favorable response to sertraline than to imipramine, and men were significantly
      more likely to show a favorable response to imipramine than to sertraline. Gender
      and type of medication were also significantly related to dropout rates; women
      who were taking imipramine and men who were taking sertraline were more likely to
      withdraw from the study. Gender differences in time to response were seen with
      imipramine, with women responding significantly more slowly than men. Comparison
      of treatment response rates by menopausal status showed that premenopausal women
      responded significantly better to sertraline than to imipramine and that
      postmenopausal women had similar rates of response to the two medications.
      CONCLUSIONS: Men and women with chronic depression show differential responsivity
      to and tolerability of SSRIs and tricyclic antidepressants. The differing
      response rates between the drug classes in women was observed primarily in
      premenopausal women. Thus, female sex hormones may enhance response to SSRIs or
      inhibit response to tricyclics. Both gender and menopausal status should be
      considered when choosing an appropriate antidepressant for a depressed patient.

PMID- 10964862
TI  - Neuropsychological differences between first-admission schizophrenia and
      psychotic affective disorders.
AB  - OBJECTIVE: The study compared the neuropsychological functioning of patients with
      first-admission schizophrenia with that of patients with first-admission
      psychotic affective disorders. METHOD: Data came from the Suffolk County Mental
      Health Project, an epidemiological study of first-admission psychotic disorders.
      Subjects with a diagnosis of schizophrenia (N=102) and psychotic affective
      disorders, including bipolar disorder with psychotic features (N=72) and major
      depressive disorder with psychotic features (N=49), were compared on a battery of
      neuropsychological tests administered 2 years after the index admission. RESULTS:
      Subjects with schizophrenia performed worse than those with the psychotic
      affective disorders, even after adjusting the results for differences in
      demographic characteristics and general intellectual functioning. The most
      consistent differences were on tests of attention, concentration, and mental
      tracking. The two psychotic affective disorder groups were indistinguishable in
      performance on the neuropsychological tests. CONCLUSIONS: Even early in its
      course, schizophrenia is distinguishable from psychotic affective disorders by
      global and specific neuropsychological deficits. These deficits might contribute
      to the disability and poor outcome associated with schizophrenia in the mid- and
      long-term course.

PMID- 10964863
TI  - Differentiating primary from secondary negative symptoms in schizophrenia: a
      study of neuroleptic-naive patients before and after treatment.
AB  - OBJECTIVE: The study examined the primary versus secondary character of negative
      symptoms in a group of first-episode, neuroleptic-naive psychotic patients before
      and after they started neuroleptic treatment. METHOD: Forty-seven inpatients with
      a first episode of schizophrenia or related psychotic disorders were examined for
      the presence of negative symptoms, psychosis, depression, and parkinsonism at
      admission to an inpatient psychiatric unit, before receiving neuroleptics, and at
      discharge an average 3.3 weeks later, after starting neuroleptic treatment.
      RESULTS: Although patients' mean scores on measures of positive, negative, and
      depressive symptoms decreased significantly over the treatment period, the mean
      rating of nonakinetic parkinsonism worsened. The mean rating of akinetic
      parkinsonism did not change significantly over the treatment period. Negative
      symptoms at admission were not predicted by positive or depressive symptoms at
      admission. Residual negative symptoms at discharge were mainly predicted by
      negative symptoms at admission (i.e., primary symptoms) and to a negligible
      degree by residual positive and depressive symptoms. Change in negative symptoms
      over the observation period was predicted to a marginal degree by change in
      depressive symptoms. CONCLUSIONS: Negative symptoms rated during a first
      psychotic episode before and after starting antipsychotic treatment are mainly
      primary in character and should be considered as a direct manifestation of the
      basic dysfunctions of schizophrenia.

PMID- 10964864
TI  - Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric
      differences in brain structure.
AB  - OBJECTIVE: Although childhood-onset schizophrenia is rare, children with brief
      psychotic symptoms and prominent emotional disturbances commonly present
      diagnostic and treatment problems. Quantitative anatomic brain magnetic resonance
      images (MRIs) of a subgroup of children with psychotic disorder not otherwise
      specified were compared with those of children with childhood-onset schizophrenia
      and healthy comparison subjects. METHOD: Anatomic MRIs were obtained for 71
      patients (44 with childhood-onset schizophrenia and 27 with psychotic disorder
      not otherwise specified) and 106 healthy volunteers. Most patients had been
      treated with neuroleptics. Volumetric measurements for the cerebrum, anterior
      frontal region, lateral ventricles, corpus callosum, caudate, putamen, globus
      pallidus, and midsagittal thalamic area were obtained. RESULTS: Patients had a
      smaller total cerebral volume than healthy comparison subjects. Analysis of
      covariance for total cerebral volume and age found that lateral ventricles were
      larger in both patient groups than in healthy comparison subjects and that
      schizophrenia patients had a smaller midsagittal thalamic area than both subjects
      with psychotic disorder not otherwise specified and healthy comparison subjects.
      CONCLUSIONS: Pediatric patients with psychotic disorder not otherwise specified
      showed a pattern of brain volumes similar to those found in childhood-onset
      schizophrenia. Neither group showed a decrease in volumes of temporal lobe
      structures. Prospective longitudinal magnetic resonance imaging and clinical
      follow-up studies of both groups are currently underway to further validate the
      distinction between these two disorders.

PMID- 10964865
TI  - Brain abnormalities in early-onset schizophrenia spectrum disorder observed with
      statistical parametric mapping of structural magnetic resonance images.
AB  - OBJECTIVE: The purpose of this study was to assess neuroanatomic abnormalities in
      children and adolescents with childhood-onset schizophrenia by using whole-brain
      voxel-based morphometric analyses. Previous volumetric studies of brain
      abnormalities in childhood-onset schizophrenia have revealed anomalies similar to
      those in subjects with adult-onset schizophrenia. Specifically, low cerebral
      volume, high ventricular volume, and thalamic, basal ganglia, callosal, and
      temporal lobe abnormalities have been observed in childhood-onset schizophrenia.
      Relatively few anatomical structures have been delineated and measured in this
      rare population, partly because of the labor involved in the slice-by-slice
      region definition required of conventional volumetric image analyses. METHOD: The
      subjects were 10 normal children and adolescents and nine children and
      adolescents with early-onset schizophrenia (mean age at diagnosis, 11.0 years;
      range, 7-16 years). The authors conducted voxel-by-voxel and volumetric
      statistical analyses of high-resolution structural magnetic resonance images.
      RESULTS: Statistical parametric maps of gray matter, white matter, and CSF
      differences between the groups revealed that the subjects with early-onset
      schizophrenia had larger ventricles, predominantly in the posterior horns of the
      lateral ventricles, and midcallosal, posterior cingulate, caudate, and thalamic
      abnormalities. Volumetric analyses of the lateral ventricles in native image data
      space confirmed significantly higher volume in posterior, but not anterior,
      regions. Randomization tests confirmed the overall statistical significance of
      the group differences and validity of the parametric maps. CONCLUSIONS: These
      findings are generally consistent with the findings of other research groups, but
      localization of enlarged ventricles specific to the posterior region may be a new
      finding in the literature on childhood-onset schizophrenia.

PMID- 10964867
TI  - Clarifying the relationship between unexplained chronic fatigue and psychiatric
      morbidity: results from a community survey in Great Britain.
AB  - OBJECTIVE: The study examined the associations between several sociodemographic
      and psychosocial variables and unexplained chronic fatigue in the community
      before and after adjustment for psychiatric morbidity and determined the
      prevalence of fatigue and rate of disability resulting from fatigue in the
      general population. METHOD: The study is a secondary analysis of 1993 data from a
      household survey of psychiatric morbidity conducted by the Office for Population
      Censuses and Surveys in Great Britain. The survey included 12,730 subjects age 16
      64 years. Unexplained chronic fatigue was used as the dependent variable in a
      logistic regression analysis, with various sociodemographic and psychosocial
      variables and psychiatric morbidity as the independent variables. Psychiatric
      morbidity was assessed by using the Revised Clinical Interview Schedule. Fatigue
      was measured by using the fatigue section of the Revised Clinical Interview
      Schedule. RESULTS: A total of 10,108 subjects agreed to cooperate (79.4%
      participation rate). The prevalence of unexplained chronic fatigue was 9%.
      Subjects with psychiatric morbidity had higher rates of fatigue. Adjustment for
      psychiatric morbidity had a minor effect on the associations between
      sociodemographic factors and chronic fatigue. After adjustment, older subjects,
      women, and couples with children had higher rates of fatigue. Single subjects,
      widowed subjects, adults living with parents, and economically inactive subjects
      had lower rates of fatigue. Fatigue was associated with considerable disability,
      but most of this disability was explained by the association between fatigue and
      psychiatric morbidity. CONCLUSIONS: Unexplained chronic fatigue is a common
      condition, strongly associated with psychiatric morbidity. The close relationship
      between fatigue and psychiatric morbidity should not obscure the possibility of
      differences as well as similarities in their etiologies.

PMID- 10964866
TI  - Understanding disability in mental and general medical conditions.
AB  - OBJECTIVE: This study characterized the prevalence, characteristics, and impact
      of mental and general medical disabilities in the United States. METHOD: The 1994
      1995 National Health Interview Survey of Disability was the largest disability
      survey ever conducted in the United States. A national sample was screened for
      disability, defined as limitation or inability to participate in a major life
      activity. Analyses compared cohorts who attributed their disability to physical,
      mental, or combined conditions. RESULTS: Of 106,573 adults, 1.1% reported
      functional disability from mental conditions, 4.8% from general medical
      conditions, and 1.2% from combined mental and general medical conditions.
      Disabilities attributed to a mental condition were predominantly associated with
      social and cognitive difficulties, those attributed to general medical conditions
      with physical limitations, and combined disabilities with deficits spanning
      multiple domains. In multivariate models, comorbid medical and mental conditions
      were associated with a twofold increase in odds of unemployment and a two-thirds
      increase in odds of support on disability payments compared to respondents with a
      single form of disability. More than half the nonworking disabled reported that
      economic, social, and job-based barriers contributed to their inability to work.
      One-fourth of working disabled people reported discrimination on the basis of
      their disability during the past 5 years. CONCLUSIONS: An estimated three million
      Americans (one-third of disabled people) reported that a mental condition
      contributes to their disability. Mental, general medical, and combined conditions
      are associated with unique patterns of functional impairment. Social and economic
      factors and job discrimination may exacerbate the functional impairments
      resulting from clinical syndromes.

PMID- 10964868
TI  - Cerebrovascular risk factors and 1-year depression outcome in older primary care
      patients.
AB  - OBJECTIVE: A model in which cerebrovascular disease contributes to the
      pathogenesis of depression in later life was the basis of the authors' hypothesis
      that cerebrovascular risk factors at intake are independently associated with
      depression at 1-year follow-up. METHOD: The subjects were 247 patients aged 60
      years or older in primary care practices. The study measures were completed at
      intake and 1-year follow-up. Multiple regression techniques were used to
      determine the independent association of initial cerebrovascular risk factors
      with depressive symptoms and diagnoses at 1 year. RESULTS: The authors found that
      the severity of initial cumulative cerebrovascular risk factors was significantly
      independently associated with 1-year depressive symptoms and diagnoses, but not
      after also controlling for overall medical burden. CONCLUSIONS: The results lend
      some support to the cerebrovascular model of depression.

PMID- 10964869
TI  - Does incomplete recovery from first lifetime major depressive episode herald a
      chronic course of illness?
AB  - OBJECTIVE: This study investigated the influence of incomplete recovery from
      first lifetime major depressive episodes on long-term outcome. METHOD: After
      their first lifetime major depressive episode, patients were divided into
      asymptomatic (N=70) and residual subthreshold depressive symptom (N=26) recovery
      groups and compared on longitudinal course during up to 12 years of prospective
      naturalistic follow-up. RESULTS: Patients with residual subthreshold depressive
      symptoms during recovery had significantly more severe and chronic future
      courses. Those with residual symptoms relapsed to major and minor depressive
      episodes faster and had more recurrences, shorter well intervals, and fewer
      symptom-free weeks during follow-up than asymptomatic patients. CONCLUSIONS:
      Resolution of major depressive episodes with residual subthreshold depressive
      symptoms, even the first lifetime episode, appears to be the first step of a more
      severe, relapsing, and chronic future course. When ongoing subthreshold symptoms
      continue after major depressive episodes, the illness is still active, and
      continued treatment is strongly recommended.

PMID- 10964870
TI  - Efficiency of the stimulus characteristics of ECT.
AB  - OBJECTIVE: Greater ECT stimulus efficiency allows for a lower stimulus dose and
      should diminish the side effects of ECT. METHOD: Four different ECT stimuli of
      identical charge (average mC=2.5 times age) with pulse widths of 0.5 msec and 1
      msec and frequencies of 30 Hz and 60 Hz, respectively, were compared for
      efficiency. The stimuli were applied in a balanced order to each of 24 subjects.
      Asymmetric bilateral electrode placement was used. RESULTS: Peak heart rates were
      higher with the 0.5-msec pulse width than the 1-msec pulse width. Seizure
      induction was more successful with the 0. 5-msec pulse width than the 1-msec
      pulse width. Stimulus frequency had no effect on heart rate or seizure induction.
      CONCLUSIONS: The pulse width of 0.5 msec is more efficient than the 1-msec pulse
      width. The "half-age" dose for the first bilateral ECT treatment is usually
      successful for subsequent ECTs when the 0.5-msec pulse width is used.

PMID- 10964871
TI  - Brain kinetics of paroxetine and fluoxetine on the third day of placebo
      substitution: a fluorine MRS study.
AB  - OBJECTIVE: This study tested whether a relationship exists between concentration
      and response following discontinuation of selective serotonin reuptake
      inhibitors. METHOD: Eight patients with remitted major depression who were taking
      20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3
      days. Serum drug and brain fluorine levels were obtained before and after placebo
      substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain
      fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared
      with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus
      fluorinated metabolites). Among patients taking paroxetine, adverse events during
      placebo substitution correlated highly with steady-state brain drug levels.
      CONCLUSIONS: The correlation of clinical effects with brain drug levels in the
      paroxetine group suggests that relationships between drug response and brain drug
      concentrations merit further investigation.

PMID- 10964872
TI  - Sex differences in response to lithium treatment.
AB  - OBJECTIVE: Although sex differences occur with some psychotropic drug treatments,
      they are not well defined for mood-stabilizing agents, including lithium. The
      authors' goal was to investigate whether there are differences between the sexes
      in response to lithium. METHOD: Studies identified in a literature search were
      analyzed for reports of sex differences in clinical response to lithium in major
      affective syndromes. RESULTS: Data from 17 studies published in 1967-1998,
      involving 1,548 adults treated with lithium for a mean of 38.6 months (SD=30.5),
      yielded similar weighted response rates to lithium in 1,043 women (65.6% [N=684])
      and 505 men (61.0% [N=308]). CONCLUSIONS: The results indicate little difference
      between the sexes in clinical response to lithium treatment of bipolar and
      related affective disorders.

PMID- 10964873
TI  - Congenital dermatoglyphic malformations and psychosis: a twin study.
AB  - OBJECTIVE: In a previous twin study, congenital dermatoglyphic abnormalities,
      such as ridge dissociations and abnormalities of palmar flexion creases, were
      more prevalent in twins with psychotic and related disorders than in comparison
      twins. This study was an attempt to replicate that finding in an independent
      study group. METHOD: Ridge dissociations and abnormal palmar flexion creases were
      assessed in monozygotic pairs concordant (19 pairs) and discordant (31 pairs) for
      psychosis and related disorders. RESULTS: The presence of either ridge
      dissociations or abnormal palmar flexion creases was higher in the combined group
      of affected concordant and discordant twins (37.7%), than in the nonaffected
      discordant twins (20.0%; odds ratio=2.4). In the discordant pairs, the presence
      of either abnormality was strongly associated with psychotic disorder (odds
      ratio=3.0). CONCLUSIONS: Factors affecting early fetal development may increase
      the risk for psychotic disorder. Differential exposure to such early risk factors
      may contribute to twin discordance for psychotic disorder.

PMID- 10964874
TI  - Premorbid functioning in a national population of male twins discordant for
      psychoses.
AB  - OBJECTIVE: The goal of the current study was to compare premorbid behavioral and
      cognitive functioning between co-twins discordant for psychotic disorder and
      between these pairs of twins and pairs of twins with no psychotic disorders.
      METHOD: The authors linked data from the Israeli Draft Board Registry, which
      contains cognitive and behavioral assessments of all 16-17-year-old male Israeli
      twins, with data from the National Psychiatric Hospitalization Case Registry.
      Pairs of male twins who were healthy at the time of testing but discordant for
      psychoses later on were compared with one another and with pairs of healthy male
      twins. RESULTS: The affected twins performed significantly worse than healthy
      twins on measures of individual autonomy, social functioning, and physical
      activity and nonsignificantly worse on measures of abstract reasoning. There were
      no significant differences in cognitive or behavioral scores between the co-twins
      who did or did not develop psychotic disorders. CONCLUSIONS: The authors conclude
      that these findings underscore the familial nature of behavioral and cognitive
      deficits antecedent to psychoses.

PMID- 10964875
TI  - Working memory control in patients with schizophrenia: a PET study during a
      random number generation task.
AB  - OBJECTIVE: The authors' goal was to investigate brain regions involved in the
      deficiency of working memory control processes in patients with schizophrenia.
      METHOD: Regional cerebral blood flow was measured with positron emission
      tomography in eight men with stabilized schizophrenia and eight healthy men while
      they were performing a graded random number generation task. Twelve scans were
      made for each subject. Covariations between randomness of responses and regional
      activation were analyzed. RESULTS: The pattern of covariation between randomness
      of responses and activation in the anterior cingulate and superior parietal
      regions differed between patients and healthy subjects. CONCLUSIONS: These
      results suggest a cinguloparietal dysfunction underlying the impairment of
      working memory control processes during a random number generation task in
      patients with schizophrenia.

PMID- 10964876
TI  - Characteristic regional cerebral blood flow patterns in anorexia nervosa patients
      with binge/purge behavior.
AB  - OBJECTIVE: The authors' goal was to investigate the effect of imagining food on
      the regional cerebral blood flow (rCBF) of anorexia nervosa patients with and
      without habitual binge/purge behavior. METHOD: The subjects included seven female
      patients with purely restrictive anorexia, seven female patients with anorexia
      and habitual binge/purge behavior, and seven healthy women. Single photon
      emission computed tomography examination was performed before and after the
      subjects were asked to imagine food. Changes in rCBF count ratios (percent
      change) were then calculated and compared. The subjects were also asked to assess
      their degree of fear regarding their control of food intake. RESULTS: The
      anorexia nervosa patients with habitual binge/purge behavior had a significantly
      higher percent change in the inferior, superior, prefrontal, and parietal regions
      of the right brain than the patients with purely restrictive anorexia and the
      healthy volunteers. The patients with habitual binge/purge behavior also had the
      highest level of apprehension in regard to food intake. CONCLUSIONS: Specific
      activation in cortical regions suggests an association between habitual
      binge/purge behavior and the food recognition process linked to anxiety in
      patients with anorexia nervosa.

PMID- 10964877
TI  - Paroxetine and irritable bowel syndrome.

PMID- 10964878
TI  - Lamotrigine and clozapine for bipolar disorder.

PMID- 10964879
TI  - Cyproheptadine for posttraumatic nightmares.

PMID- 10964880
TI  - Nonconvulsive status epilepticus after ECT.

PMID- 10964881
TI  - Posttraumatic stress disorder and sleep difficulty.

PMID- 10964882
TI  - Rapid-cycling bipolar disorder in children.

PMID- 10964883
TI  - Weight gain with anorexia nervosa.

PMID- 10964884
TI  - Markers for schizophrenia.

PMID- 10964885
TI  - Medication or psychotherapy for severe depression.

PMID- 10964901
TI  - Part 1: Introduction to the International Guidelines 2000 for CPR and ECC : a
      consensus on science.

PMID- 10964908
TI  - Tramtrack protein-DNA interactions. A cross-linking study.
AB  - Interaction of the Tramtrack protein from Drosophila melanogaster with DNA was
      analyzed by a cross-linking method. Tramtrack residues cross-linkable to the
      partially depurinated DNA were identified by direct sequencing. The N-terminal
      alpha-amino group of the protein DNA-binding domain was found to be the major
      product of cross-linking. The location of the N terminus on the DNA was
      determined by identification of the DNA bases that were cross-linked to the
      protein alpha-amino group. We conclude that accessory N-terminal peptide
      preceding the first zinc finger of Tramtrack directly interacts with DNA, both in
      specific and nonspecific DNA-protein complexes. Our finding explains the role in
      the protein binding of the DNA bases outside of the direct interaction with the
      zinc fingers.

PMID- 10964907
TI  - The calcium-independent receptor for alpha-latrotoxin from human and rodent
      brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain
      proteins.
AB  - Subtypes of the calcium-independent receptors for alpha-latrotoxin (CIRL1-3)
      define a distinct subgroup within the large family of the seven-transmembrane
      region cell surface receptors. The physiological function of CIRLs is unknown
      because neither extracellular ligands nor intracellular coupling proteins (G
      proteins) have been identified. Using yeast two-hybrid screening, we identified a
      novel interaction between the C termini of CIRL1 and -2 and the PSD-95/discs
      large/ZO-1 (PDZ) domain of a recently discovered multidomain protein family
      (ProSAP/SSTRIP/Shank) present in human and rat brain. In vitro, CIRL1 and CIRL2
      interacted strongly with the PDZ domain of ProSAP1. The specificity of this
      interaction has been verified by in vivo experiments using solubilized rat brain
      membrane fractions and ProSAP1 antibodies; only CIRL1, but not CIRL2, was co
      immunoprecipitated with ProSAP1. In situ hybridization revealed that ProSAP1 and
      CIRL1 are co-expressed in the cortex, hippocampus, and cerebellum. Colocalization
      was also observed at the subcellular level, as both CIRL1 and ProSAP1 are
      enriched in the postsynaptic density fraction from rat brain. Expression of all
      three CIRL isoforms is highly regulated during postnatal brain development, with
      CIRL3 exhibiting its highest expression levels immediately after birth, followed
      by CIRL2 and finally CIRL1 in aged rats.

PMID- 10964909
TI  - Macrophage colony-stimulating factor rapidly enhances beta-migrating very low
      density lipoprotein metabolism in macrophages through activation of a Gi/o
      protein signaling pathway.
AB  - Previous studies have examined lipoprotein metabolism by macrophages following
      prolonged exposure (>24 h) to macrophage colony-stimulating factor (M-CSF).
      Because M-CSF activates several signaling pathways that could rapidly affect
      lipoprotein metabolism, we examined whether acute exposure of macrophages to M
      CSF alters the metabolism of either native or modified lipoproteins. Acute
      incubation of cultured J774 macrophages and resident mouse peritoneal macrophages
      with M-CSF markedly enhanced low density lipoproteins (LDL) and beta-migrating
      very low density lipoproteins (beta-VLDL) stimulated cholesteryl [(3)H]oleate
      deposition. In parallel, M-CSF treatment increased the association and
      degradation of (125)I-labeled LDL or beta-VLDL without altering the amount of
      lipoprotein bound to the cell surface. The increase in LDL and beta-VLDL
      metabolism did not reflect a generalized effect on lipoprotein endocytosis and
      metabolism because M-CSF did not alter cholesterol deposition during incubation
      with acetylated LDL. Moreover, M-CSF did not augment beta-VLDL cholesterol
      deposition in macrophages from LDL receptor (-/-) mice, indicating that the
      effect of M-CSF was mediated by the LDL receptor. Incubation of macrophages with
      pertussis toxin, a specific inhibitor of G(i/o) protein signaling, had no effect
      on cholesterol deposition during incubation with beta-VLDL alone, but completely
      blocked the augmented response promoted by M-CSF. In addition, incubation of
      macrophages with the direct G(i/o) protein activator, mastoparan, mimicked the
      effect of M-CSF by enhancing cholesterol deposition in cells incubated with beta
      VLDL, but not acetylated LDL. In summary, M-CSF rapidly enhances LDL receptor
      mediated metabolism of native lipoproteins by macrophages through activation of a
      G(i/o) protein signaling pathway. Together, these findings describe a novel
      pathway for regulating lipoprotein metabolism.

PMID- 10964910
TI  - Involvement of tyrosine kinase activity in 1alpha,25(OH)2-vitamin D3 signal
      transduction in skeletal muscle cells.
AB  - In cultured chick skeletal muscle cells loaded with Fura-2, the tyrosine kinase
      inhibitors herbimycin A and genistein abolished both the fast inositol 1,4,5
      trisphosphatedependent Ca(2+) release from internal stores and extracellular
      Ca(2+) influx induced by 1alpha, 25(OH)(2)-vitamin D(3) (1alpha,25(OH)(2)D(3)).
      Daidzein, an inactive analog of genistein, was without effects. Tyrosine
      phosphatase inhibition by orthovanadate increased cytosolic Ca(2+). Anti
      phosphotyrosine immunoblot analysis revealed that 1alpha, 25(OH)(2)D(3) rapidly
      (0.5-10 min) stimulates in a concentrationdependent fashion (0.1-10 nm) tyrosine
      phosphorylation of several myoblast proteins, among which the major targets of
      the hormone could be immunochemically identified as phospholipase Cgamma (127
      kDa), which mediates intracellular store Ca(2+) mobilization and external Ca(2+)
      influx, and the growth-related proteins mitogen-activated protein (MAP) kinase
      (42/44 kDa) and c-myc (65 kDa). Genistein suppressed the increase in
      phosphorylation and concomitant elevation of MAPK activity elicited by the
      sterol. Both genistein and the MAPK kinase (MEK) inhibitor PD98059 abolished
      stimulation of DNA synthesis by 1alpha,25(OH)(2)D(3). The sterol-induced increase
      in tyrosine phosphorylation of c-myc, a finding not reported before for cell
      growth regulators, was totally suppressed by the specific Src inhibitor PP1.
      These results demonstrate that tyrosine phosphorylation is a previously
      unrecognized mechanism involved in 1alpha,25(OH)(2)D(3) regulation of Ca(2+)
      homeostasis in hormone target cells. In addition, the data involve tyrosine
      kinase cascades in the mitogenic effects of 1alpha, 25(OH)(2)D(3) on skeletal
      muscle cells.

PMID- 10964911
TI  - The forgotten serine. A critical role for Ser-2035.42 in ligand binding to and
      activation of the beta 2-adrenergic receptor.
AB  - Previous work in the beta(2)-adrenergic receptor demonstrated critical
      interactions between Ser-204 and Ser-207 in the fifth membrane-spanning segment
      and the meta-OH and para-OH, respectively, of catecholamine agonists (Strader, C.
      D., Candelore, M. R., Hill, W. S., Sigal, I. S., and Dixon, R. A. (1989) J. Biol.
      Chem. 264, 13572-13578). Using the substituted cysteine accessibility method in
      the beta(2)-adrenergic receptor, we have found that in addition to Ser-204 and
      Ser-207, Ser-203 is also accessible on the surface of the binding-site crevice
      and is occluded by bound agonist. Mutation of Ser-203 to Ala, Val, or Cys reduced
      the binding affinity and adenylyl cyclase-activating potency of agonists
      containing a meta-OH, whereas their affinities and potencies were largely
      preserved by mutation of Ser-203 to Thr, which maintained an OH at this position.
      Thus both Ser-203 and Ser-204 appear to interact with the meta-OH of
      catecholamines, perhaps through a bifurcated H bond. Furthermore, the removal of
      the OH at position 203 led to a significant loss of affinity of antagonists with
      nitrogen in their heterocyclic ring structure. The greatest effect was seen with
      pindolol, a partial agonist, suggesting that a H bond between the heterocyclic
      ring and Ser-203 may play a role in partial agonism. In contrast, the affinities
      of antagonists such as propranolol or alprenolol, which have cyclic structures
      without H-bonding capability, were unaltered after mutation of Ser-203.

PMID- 10964912
TI  - Transforming growth factor-beta up-regulates the beta 5 integrin subunit
      expression via Sp1 and Smad signaling.
AB  - Integrin-mediated cell-matrix interactions play important roles in regulating
      cell function. Since transforming growth factor-beta (TGF-beta) modulates many
      osteoblast activities, we hypothesized that the growth factor acts in part by
      modulating integrin expression. TGF-beta increased cell adhesion to vitronectin
      and up-regulated the surface level of alpha(v)beta(5) via increasing beta(5)
      protein synthesis by a transcriptional mechanism. Promoter activity analysis
      demonstrated that a TGF-beta-responsive element resides between nucleotides -63
      and -44. Electrophoretic mobility shift assay and immunoprecipitation/Western
      studies indicated that the nuclear complex formed using the -66/-42
      oligonucleotide contained both Sp1/Sp3 and Smad proteins. Since nuclear Sp1/Sp3
      levels were not altered, whereas Smad levels were increased by TGF-beta, we
      investigated the roles of Smad proteins in the up-regulation of beta(5) gene
      activation. Co-transfection of cells with beta(5) promoter reporter construct and
      expression vectors for Smad3, Smad4, and Sp1 increased the stimulatory effect of
      TGF-beta. Furthermore, expression of dominant negative Smad3 or Smad4 in cells
      decreased or abolished the stimulation of beta(5) promoter activity by TGF-beta.
      Smad4 mutant also inhibited the up-regulation of surface beta(5) level by TGF
      beta. Thus, TGF-beta increases expression of the integrin beta(5) gene by
      mechanisms involving Sp1/Sp3 and Smad transcription factors.

PMID- 10964913
TI  - Human calcium-independent phospholipase A2 mediates lymphocyte proliferation.
AB  - Activation of lymphocytes induces blastogenesis and cell division which is
      accompanied by membrane lipid metabolism such as increased fatty acid turnover.
      To date little is known about the enzymatic mechanism(s) regulating this process.
      Release of fatty acids such as arachidonic acid requires sn-2-deacylation
      catalyzed by a class of enzymes known as phospholipases A(2) (PLA(2), EC ).
      Herein, we confirm that human peripheral blood B or T lymphocytes (PBL) do not
      possess measurable levels of 85-kDa PLA(2) as assessed by Western immunoblot. Low
      levels of 14-kDa PLA(2) protein and activity were detectable in the particulate
      fraction of PBL and Jurkat cells. Western immunoblot analysis indicates that PBLs
      possess the calcium-independent PLA(2) (iPLA(2)) protein. Calcium-independent sn
      2-acylhydrolytic activity was measurable in PBL cytosols and could be inhibited
      by the selective iPLA(2) inhibitor bromoenol lactone. Mitogen activation of PBLs
      resulted in maintenance of activity levels which remained constant over 72 h
      suggesting an important role for iPLA(2) in this proliferative process. Indeed,
      evaluation of iPLA(2) activity in cell cycle-arrested Jurkat T cell fractions
      revealed the highest iPLA(2) levels occurring at the G(2)/M phase. Addition of
      the iPLA(2) inhibitors, bromoenol lactone, or arachidonyl trifluoromethyl ketone
      (AAOCF(3)), inhibited both mitogen-induced PBL as well as Jurkat T cell
      proliferation. Moreover, specific depletion of iPLA(2) protein by antisense
      treatment also resulted in marked suppression of cell division. Inhibition of
      Jurkat cell proliferation was not associated with arrest at a particular phase of
      the cell cycle nor was it associated with apoptosis as assessed by flow
      cytometry. These findings provide the first evidence that iPLA(2) plays a key
      role in the lymphocyte proliferative response.

PMID- 10964914
TI  - CD47, a ligand for the macrophage fusion receptor, participates in macrophage
      multinucleation.
AB  - The macrophage fusion receptor (MFR), also called P84/BIT/SIRPalpha/SHPS-1, is a
      transmembrane glycoprotein that belongs to the superfamily of immunoglobulins.
      Previously, we showed that MFR expression is highly induced at the onset of
      fusion in macrophages, and that MFR appears to play a role in macrophage
      macrophage adhesion/fusion leading to multinucleation. The recent finding that
      IAP/CD47 acts as a ligand for MFR led us to hypothesize that it interacts with
      CD47 at the onset of cell-cell fusion. CD47 is a transmembrane glycoprotein,
      which, like MFR, belongs to the superfamily of immunoglobulins. We show that
      macrophages express the hemopoietic form of CD47, the expression of which is
      induced at the onset of fusion, but to a lower level than MFR. A glutathione S
      transferase CD47 fusion protein engineered to contain the extracellular domain of
      CD47, binds macrophages, associates with MFR, and prevents multinucleation. CD47
      and MFR associate via their amino-terminal immunoglobulin variable domain. Of the
      nine monoclonal antibodies raised against the extracellular domain of CD47, three
      block fusion, as well as MFR-CD47 interaction, whereas the others have no effect.
      Together, these data suggest that CD47 is involved in macrophage multinucleation
      by virtue of interacting with MFR during adhesion/fusion.

PMID- 10964915
TI  - Niemann-pick type C1 (NPC1) overexpression alters cellular cholesterol
      homeostasis.
AB  - The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular
      trafficking of low density lipoprotein cholesterol, but its role in regulation of
      sterol homeostasis is not well understood. To characterize further the function
      of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines
      overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases
      the rate of trafficking of low density lipoprotein cholesterol to the endoplasmic
      reticulum and the rate of delivery of endosomal cholesterol to the plasma
      membrane (PM). CHO/NPC1 cells exhibit a 1.5-fold increase in total cellular
      cholesterol and up to a 2.9-fold increase in PM cholesterol. This increase in PM
      cholesterol is closely paralleled by a 3-fold increase in de novo cholesterol
      synthesis. Inhibition of cholesterol synthesis results in marked redistribution
      of PM cholesterol to intracellular sites, suggesting an unsuspected role for NPC1
      in internalization of PM cholesterol. Despite elevated total cellular
      cholesterol, CHO/NPC1 cells exhibit increased cholesterol synthesis, which may be
      attributable to both resistance to oxysterol suppression of sterol-regulated gene
      expression and to reduced endoplasmic reticulum cholesterol levels under basal
      conditions. Taken together, these studies provide important new insights into the
      role of NPC1 in the determination of the levels and distribution of cellular
      cholesterol.

PMID- 10964916
TI  - Characterization of the yeast Cdc7p/Dbf4p complex purified from insect cells. Its
      protein kinase activity is regulated by Rad53p.
AB  - The yeast Saccharomyces cerevisiae Cdc7p/Dbf4p protein kinase complex was
      purified to near homogeneity from insect cells. The complex efficiently
      phosphorylated yeast Mcm2p and less efficiently the remaining Mcm proteins or
      other replication proteins. Significantly, when pretreated with alkaline
      phosphatase, Mcm2p became completely inactive as a substrate, suggesting that it
      must be phosphorylated by other protein kinase(s) to be a substrate for the
      Cdc7p/Dbf4p complex. Mutant Cdc7p/Dbf4p complexes containing either Cdc7-1p or
      Dbf4-1 approximately 5p were also partially purified from insect cells and
      characterized in vitro. Furthermore, the autonomously replicating sequence
      binding activity of various dbf4 mutants was also analyzed. These studies suggest
      that the autonomously replicating sequence-binding and Cdc7p protein kinase
      activation domains of Dbf4p collaborate to form an active Cdc7p/Dbf4p complex and
      function during S phase in S. cerevisiae. It is shown that Rad53p phosphorylates
      the Cdc7p/Dbf4p complex in vitro and that this phosphorylation greatly inhibits
      the kinase activity of Cdc7p/Dbf4p. This result suggests that Rad53p controls the
      initiation of chromosomal DNA replication by regulating the protein kinase
      activity associated with the Cdc7p/Dbf4p complex.

PMID- 10964917
TI  - Identification of shc as the primary protein binding to the tyrosine
      phosphorylated beta 3 subunit of alpha IIbbeta 3 during outside-in integrin
      platelet signaling.
AB  - Outside-in signaling mediated by the integrin alpha(IIb)beta(3) (GPIIbIIIa) is
      critical to platelet function and has been shown to involve the phosphorylation
      of tyrosine residues on the cytoplasmic tail of beta(3). To identify proteins
      that bind directly to phosphorylated beta(3), we utilized an affinity column
      consisting of a peptide modeled on the tyrosine-phosphorylated cytoplasmic domain
      of beta(3). Tandem mass spectrometric sequencing and immunoblotting demonstrated
      that Shc was the primary protein binding to phosphorylated beta(3). To determine
      the involvement of Shc in outside-in alpha(IIb)beta(3) signaling, the
      phosphorylation of Shc during platelet aggregation was examined; transient Shc
      phosphorylation was observed when thrombin-stimulated platelets were allowed to
      aggregate or when aggregation was induced by an LIBS (ligand-induced binding
      site) antibody, D3. Moreover, Shc was co-immunoprecipitated with tyrosine
      phosphorylated beta(3) in detergent lysates of aggregated platelets. Using
      purified, recombinant protein, it was found that the binding of Shc to
      monophosphorylated (C-terminal tyrosine) and diphosphorylated beta(3) peptides
      was direct, demonstrating Shc recognition motifs on phospho-beta(3). Aggregation
      induced Shc phosphorylation was also observed to be robust in platelets from wild
      type mice, but not in those from mice expressing (Y747F,Y759F) beta(3), which are
      defective in outside-in alpha(IIb)beta(3) signaling. Thus, Shc is the primary
      downstream signaling partner of beta(3) in its tyrosine phosphorylation outside
      in signaling pathway.

PMID- 10964918
TI  - The ubiquitin-proteasome pathway mediates the regulated degradation of mammalian
      3-hydroxy-3-methylglutaryl-coenzyme A reductase.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), the key regulatory enzyme
      in the mevalonate (MVA) pathway, is rapidly degraded in mammalian cells
      supplemented with sterols or MVA. This accelerated turnover was blocked by N
      acetyl-leucyl-leucyl-norleucinal (ALLN), MG-132, and lactacystin, and to a lesser
      extent by N-acetyl-leucyl-leucyl-methional (ALLM), indicating the involvement of
      the 26 S proteasome. Proteasome inhibition led to enhanced accumulation of high
      molecular weight polyubiquitin conjugates of HMGR and of HMGal, a chimera between
      the membrane domain of HMGR and beta-galactosidase. Importantly, increased
      amounts of polyubiquitinated HMGR and HMGal were observed upon treating cells
      with sterols or MVA. Cycloheximide inhibited the sterol-stimulated degradation of
      HMGR concomitantly with a marked reduction in polyubiquitination of the enzyme.
      Inhibition of squalene synthase with zaragozic acid blocked the MVA- but not
      sterol-stimulated ubiquitination and degradation of HMGR. Thus, similar to yeast,
      the ubiquitin-proteasome pathway is involved in the metabolically regulated
      turnover of mammalian HMGR. Yet, the data indicate divergence between yeast and
      mammals and suggest distinct roles for sterol and nonsterol metabolic signals in
      the regulated ubiquitination and degradation of mammalian HMGR.

PMID- 10964919
TI  - Mutational analysis of affinity and selectivity of kringle-tetranectin
      interaction. Grafting novel kringle affinity ontp the trtranectin lectin
      scaffold.
AB  - C-type lectin-like domains are found in many proteins, where they mediate binding
      to a wide diversity of compounds, including carbohydrates, lipids, and proteins.
      The binding of a C-type lectin-like domain to a ligand is often influenced by
      calcium. Recently, we have identified a site in the C-type lectin-like domain of
      tetranectin, involving Lys-148, Glu-150, and Asp-165, which mediates calcium
      sensitive binding to plasminogen kringle 4. Here, we investigate the effect of
      conservative substitutions of these and a neighboring amino acid residue.
      Substitution of Thr-149 in tetranectin with a tyrosine residue considerably
      increases the affinity for plasminogen kringle 4, and, in addition, confers
      affinity for plasminogen kringle 2. As shown by isothermal titration calorimetry
      analysis, this new interaction is stronger than the binding of wild-type
      tetranectin to plasminogen kringle 4. This study provides further insight into
      molecular determinants of importance for binding selectivity and affinity of C
      type lectin kringle interactions.

PMID- 10964920
TI  - Functional characterization of a lysosomal sorting motif in the cytoplasmic tail
      of HLA-DObeta.
AB  - HLA-DO is an intracellular non-classical class II major histocompatibility
      complex molecule expressed in the endocytic pathway of B lymphocytes, which
      regulates the loading of antigenic peptides onto classical class II molecules
      such as HLA-DR. The activity of HLA-DO is mediated through its interaction with
      the peptide editor HLA-DM. Here, our results demonstrate that although HLA-DO is
      absolutely dependent on its association with DM to egress the endoplasmic
      reticulum, the cytoplasmic portion of its beta chain encodes a functional
      lysosomal sorting signal. By confocal microscopy and flow cytometry analysis, we
      show that reporter transmembrane molecules fused to the cytoplasmic tail of HLA
      DObeta accumulated in Lamp-1(+) vesicles of transfected HeLa cells. Mutagenesis
      of a leucine-leucine motif abrogated lysosomal accumulation and resulted in cell
      surface redistribution of reporter molecules. Finally, we show that mutation of
      the di-leucine sequence in DObeta did not alter its lysosomal sorting when
      associated with DM molecules. Taken together, these results demonstrate that
      lysosomal expression of the DO-DM complex is mediated primarily by the tyrosine
      based motif of HLA-DM and suggest that the DObeta-encoded motif is involved in
      the fine-tuning of the intracellular sorting.

PMID- 10964921
TI  - Expression patterns of the multiple transcripts from the folylpolyglutamate
      synthetase gene in human leukemias and normal differentiated tissues.
AB  - Folylpoly-gamma-glutamate synthetase (FPGS) catalyzes the activation of folate
      antimetabolites in mammalian tissues and tumors. We have determined the sequence,
      abundance, and function of human FPGS transcripts and found some striking
      differences to transcription of the mouse gene that allow production of FPGS
      isoforms in mouse liver and dividing tissues. Multiple human transcripts were
      identified, including the homolog of the mouse transcripts that initiate at two
      upstream exons. However, the human FPGS upstream promoter is infrequently used,
      and transcripts from this promoter include sequences homologous with only one of
      the upstream exons found in the mouse. The downstream promoter generates an array
      of transcripts, some of which do not produce active enzyme, a phenomenon not seen
      in the mouse. Hence, the dual promoter mechanism directing expression of FPGS
      isozymes in mouse tissues is not conserved in humans, and, unlike the mouse
      downstream promoter, the human downstream promoter is active in both dividing and
      differentiated tissues. This study raises questions about the differences in
      function served by the two mouse FPGS isozymes and how, or if, human tissues
      fulfill these functions. How humans and mice produce FPGS in only a subset of
      tissues using such different promoter structures also becomes a central issue.

PMID- 10964922
TI  - c-Abl has high intrinsic tyrosine kinase activity that is stimulated by mutation
      of the Src homology 3 domain and by autophosphorylation at two distinct
      regulatory tyrosines.
AB  - Using the specific Abl tyrosine kinase inhibitor STI 571, we purified
      unphosphorylated murine type IV c-Abl and measured the kinetic parameters of c
      Abl tyrosine kinase activity in a solution with a peptide-based assay.
      Unphosphorylated c-Abl exhibited substantial peptide kinase activity with K(m) of
      204 microm and V(max) of 33 pmol min(-1). Contrary to previous observations using
      immune complex kinase assays, we found that a transforming c-Abl mutant with a
      Src homology 3 domain point mutation (P131L) had significantly (about 6-fold)
      higher intrinsic kinase activity than wild-type c-Abl (K(m) = 91 microm, V(max) =
      112 pmol min(-1)). Autophosphorylation stimulated the activity of wild-type c-Abl
      about 18-fold and c-Abl P131L about 3.6-fold, resulting in highly active kinases
      with similar catalytic rates. The autophosphorylation rate was dependent on Abl
      protein concentration consistent with an intermolecular reaction. A tyrosine to
      phenylalanine mutation (Y412F) at the c-Abl residue homologous to the c-Src
      catalytic domain autophosphorylation site impaired the activation of wild-type c
      Abl by 90% but reduced activation of c-Abl P131L by only 45%. Mutation of a
      tyrosine (Tyr-245) in the linker region between the Src homology 2 and catalytic
      domains that is conserved among the Abl family inhibited the autophosphorylation
      induced activation of wild-type c-Abl by 50%, whereas the c-Abl Y245F/Y412F
      double mutant was minimally activated by autophosphorylation. These results
      support a model where c-Abl is inhibited in part through an intramolecular Src
      homology 3-linker interaction and stimulated to full catalytic activity by
      sequential phosphorylation at Tyr-412 and Tyr-245.

PMID- 10964923
TI  - Cyclosporin A inhibits creatine uptake by altering surface expression of the
      creatine transporter.
AB  - The immunosuppressive drug cyclosporin A (CsA) inhibited the hCRT-1 cDNA-induced
      creatine uptake in Xenopus oocytes and the endogenous creatine uptake in cultured
      C(2)C(12) muscle cells in a dose- and time-dependent manner. FK506, another
      potent immunosuppressant, was unable to mimic the effect of CsA suggesting that
      the inhibitory effect of CsA was specific. To delineate the mechanism underlying,
      we investigated the effect of CsA on the K(m) and V(max) of creatine transport
      and also on the cell surface distribution of the creatine transporter. Although
      CsA treatment did not affect the K(m) (20-24 microm) for creatine, it
      significantly decreased the V(max) of creatine uptake in both oocytes and muscle
      cells. CsA treatment reduced the cell surface expression level of the creatine
      transporter in the muscle cells by approximately 60% without significantly
      altering its total expression level, and the reduction in the cell surface
      expression paralleled the decrease in creatine uptake. Taken together, our
      results suggest that CsA inhibited creatine uptake by altering the surface
      abundance of the creatine transporter. We propose that CsA impairs the targeting
      of the creatine transporter by inhibiting the function of an associated
      cyclophilin, resulting in an apparent loss in surface expression of the creatine
      transporter. Our results also suggest that prolonged exposure to CsA may result
      in chronically creatine-depleted muscle, which may be a cause for the development
      of CsA-associated clinical myopathies in organ transplant patients.

PMID- 10964924
TI  - Thrombospondin mediates focal adhesion disassembly through interactions with cell
      surface calreticulin.
AB  - Thrombospondin induces reorganization of the actin cytoskeleton and restructuring
      of focal adhesions. This activity is localized to amino acids 17-35 in the N
      terminal heparin-binding domain of thrombospondin and can be replicated by a
      peptide (hep I) with this sequence. Thrombospondin/hep I stimulate focal adhesion
      disassembly through a mechanism involving phosphoinositide 3-kinase activation.
      However, the receptor for this thrombospondin sequence is unknown. We now report
      that calreticulin on the cell surface mediates focal adhesion disassembly by
      thrombospondin/hep I. A 60-kDa protein from endothelial cell detergent extracts
      has homology and immunoreactivity to calreticulin, binds a hep I affinity column,
      and neutralizes thrombospondin/hep I-mediated focal adhesion disassembly.
      Calreticulin on the cell surface was confirmed by biotinylation, confocal
      microscopy, and by fluorescence-activated cell sorting analyses. Thrombospondin
      and calreticulin potentially bind through the hep I sequence, since
      thrombospondin-calreticulin complex formation can be blocked specifically by hep
      I peptide. Antibodies to calreticulin and preincubation of thrombospondin/hep I
      with glutathione S-transferase-calreticulin block thrombospondin/hep I-mediated
      focal adhesion disassembly and phosphoinositide 3-kinase activation, suggesting
      that calreticulin is a component of the thrombospondin-induced signaling cascade
      that regulates cytoskeletal organization. These data identify both a novel
      receptor for the N terminus of thrombospondin and a distinct role for cell
      surface calreticulin in cell adhesion.

PMID- 10964925
TI  - Dm1-MMP, a matrix metalloproteinase from Drosophila with a potential role in
      extracellular matrix remodeling during neural development.
AB  - We have cloned and characterized a cDNA encoding Dm1-MMP, the first matrix
      metalloproteinase (MMP) identified in Drosophila melanogaster. The isolated cDNA
      encodes a protein of 541 residues that has a domain organization identical to
      that of most vertebrate MMPs including a signal sequence, a prodomain with the
      activation locus, a catalytic domain with a zinc-binding site, and a COOH
      terminal hemopexin domain. Northern blot analysis of Dm1-MMP expression in
      embryonic and larval adult tissues revealed a strong expression level in the
      developing embryo at 10-22 h, declining thereafter and being undetectable in
      adults. Western blot analysis confirmed the presence of pro- and active forms of
      Dm1-MMP in vivo during larval development. In situ hybridization experiments
      demonstrated that Dm1-MMP is expressed in a segmented pattern in cell clusters at
      the midline during embryonic stage 12-13, when neurons of the central nervous
      system start to arise. Recombinant Dm1-MMP produced in Escherichia coli exhibits
      a potent proteolytic activity against synthetic peptides used for analysis of
      vertebrate MMPs. This activity is inhibited by tissue inhibitors of
      metalloproteinases and by synthetic MMP inhibitors such as BB-94. Furthermore,
      Dm1-MMP is able to degrade the extracellular matrix and basement membrane
      proteins fibronectin and type IV collagen. On the basis of these data, together
      with the predominant expression of Dm1-MMP in embryonic neural cells, we propose
      that this enzyme may be involved in the extracellular matrix remodeling taking
      place during the development of the central nervous system in Drosophila.

PMID- 10964926
TI  - Identification of the putrescine recognition site on polyamine transport protein
      PotE.
AB  - The PotE protein can catalyze both uptake and excretion of putrescine. The K(m)
      values of putrescine for uptake and excretion are 1.8 and 73 microm,
      respectively. Uptake of putrescine is dependent on the membrane potential,
      whereas excretion involves putrescine-ornithine antiporter activity. Amino acids
      involved in both activities were identified using mutated PotE proteins. It was
      found that Cys(62), Trp(201), Trp(292), and Tyr(425) were strongly involved in
      both activities, and that Tyr(92), Cys(210), Cys(285), and Cys(286) were
      moderately involved in the activities. Mutations of Tyr(78), Trp(90), and
      Trp(422) mainly affected uptake activity, and the K(m) values for putrescine
      uptake by these PotE mutants increased greatly, indicating that these amino acids
      are involved in the high affinity uptake of putrescine by PotE. Mutations of
      Lys(301) and Tyr(308) mainly affected excretion activity (putrescine-ornithine
      antiporter activity), and excretion by these mutants was not stimulated by
      ornithine, indicating that these amino acids are involved in the recognition of
      ornithine. It was found that the putrescine and ornithine recognition site on
      PotE is located at the cytoplasmic surface and the vestibule of the pore
      consisting of 12 transmembrane segments. Based on the results of competition
      experiments with various putrescine analogues and the disulfide cross-linking of
      PotE between cytoplasmic loops and the COOH terminus, a model of the putrescine
      recognition site on PotE consisting of the identified amino acids is presented.

PMID- 10964927
TI  - A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of
      peptide methionine sulfoxide reductase from Escherichia coli.
AB  - Methionine oxidation into methionine sulfoxide is known to be involved in many
      pathologies and to exert regulatory effects on proteins. This oxidation can be
      reversed by a ubiquitous monomeric enzyme, the peptide methionine sulfoxide
      reductase (MsrA), whose activity in vivo requires the thioredoxin-regenerating
      system. The proposed chemical mechanism of Escherichia coli MsrA involves three
      Cys residues (positions 51, 198, and 206). A fourth Cys (position 86) is not
      important for catalysis. In the absence of a reducing system, 2 mol of methionine
      are formed per mole of enzyme for wild type and Cys-86 --> Ser mutant MsrA,
      whereas only 1 mol is formed for mutants in which either Cys-198 or Cys-206 is
      mutated. Reduction of methionine sulfoxide is shown to proceed through the
      formation of a sulfenic acid intermediate. This intermediate has been
      characterized by chemical probes and mass spectrometry analyses. Together, the
      results support a three-step chemical mechanism in vivo: 1) Cys-51 attacks the
      sulfur atom of the sulfoxide substrate leading, via a rearrangement, to the
      formation of a sulfenic acid intermediate on Cys-51 and release of 1 mol of
      methionine/mol of enzyme; 2) the sulfenic acid is then reduced via a double
      displacement mechanism involving formation of a disulfide bond between Cys-51 and
      Cys-198, followed by formation of a disulfide bond between Cys-198 and Cys-206,
      which liberates Cys-51, and 3) the disulfide bond between Cys-198 and Cys-206 is
      reduced by thioredoxin-dependent recycling system process.

PMID- 10964928
TI  - Binding of BiP to the processing enzyme lymphoma proprotein convertase prevents
      aggregation, but slows down maturation.
AB  - Lymphoma proprotein convertase (LPC) is a subtilisin-like serine protease of the
      mammalian proprotein convertase family. It is synthesized as an inactive
      precursor protein, and propeptide cleavage occurs via intramolecular cleavage in
      the endoplasmic reticulum. In contrast to other convertases like furin and
      proprotein convertase-1, propeptide cleavage occurs slowly. Also, both a
      glycosylated and an unglycosylated precursor are detected. Here we demonstrate
      that the unglycosylated precursor form of LPC is localized in the cytosol due to
      the absence of a signal peptide. Using a reducible cross-linker, we found that
      glycosylated pro-LPC is associated with the molecular chaperone BiP. In addition,
      we show that pro-LPC is prone to aggregation and forms large complexes linked via
      interchain disulfide bonds. BiP is associated mainly with non-aggregated pro-LPC
      and pro-LPC dimers and trimers, suggesting that BiP prevents aggregation.
      Overexpression of wild-type BiP or a dominant-negative BiP ATPase mutant resulted
      in reduced processing of pro-LPC. Taken together, these results suggest that
      binding of BiP to pro-LPC prevents aggregation, but results in slower maturation.

PMID- 10964929
TI  - Differential effects of xenoestrogens on coactivator recruitment by estrogen
      receptor (ER) alpha and ERbeta.
AB  - It has been proposed that tissue-specific estrogenic and/or antiestrogenic
      actions of certain xenoestrogens may be associated with alterations in the
      tertiary structure of estrogen receptor (ER) alpha and/or ERbeta following ligand
      binding; changes which are sensed by cellular factors (coactivators) required for
      normal gene expression. However, it is still unclear whether xenoestrogens affect
      the normal behavior of ERalpha and/or ERbeta subsequent to receptor binding. In
      view of the wide range of structural forms now recognized to mimic the actions of
      the natural estrogens, we have assessed the ability of ERalpha and ERbeta to
      recruit TIF2 and SRC-1a in the presence of 17beta-estradiol, genistein,
      diethylstilbestrol, 4-tert-octylphenol, 2',3',4', 5'-tetrachlorobiphenyl-ol, and
      bisphenol A. We show that ligand-dependent differences exist in the ability of
      ERalpha and ERbeta to bind coactivator proteins in vitro, despite the similarity
      in binding affinity of the various ligands for both ER subtypes. The enhanced
      ability of ERbeta (over ERalpha) to recruit coactivators in the presence of
      xenoestrogens was consistent with a greater ability of ERbeta to potentiate
      reporter gene activity in transiently transfected HeLa cells expressing SRC-1e
      and TIF2. We conclude that ligand-dependent differences in the ability of ERalpha
      and ERbeta to recruit coactivator proteins may contribute to the complex tissue
      dependent agonistic/antagonistic responses observed with certain xenoestrogens.

PMID- 10964930
TI  - High density lipoprotein phospholipid composition is a major determinant of the
      bi-directional flux and net movement of cellular free cholesterol mediated by
      scavenger receptor BI.
AB  - The role of high density lipoprotein (HDL) phospholipid in scavenger receptor BI
      (SR-BI)-mediated free cholesterol flux was examined by manipulating HDL(3)
      phosphatidylcholine and sphingomyelin content. Both phosphatidylcholine and
      sphingomyelin enrichment of HDL enhanced the net efflux of cholesterol from SR-BI
      expressing COS-7 cells but by two different mechanisms. Phosphatidylcholine
      enrichment of HDL increased efflux, whereas sphingomyelin enrichment decreased
      influx of HDL cholesterol. Although similar trends were observed in control
      (vector-transfected) COS-7 cells, SR-BI overexpression amplified the effects of
      phosphatidylcholine and sphingomyelin enrichment of HDL 25- and 2.8-fold,
      respectively. By using both phosphatidylcholine-enriched and phospholipase A(2)
      treated HDL to obtain HDL with a graded phosphatidylcholine content, we showed
      that SR-BI-mediated cholesterol efflux was highly correlated (r(2) = 0.985) with
      HDL phosphatidylcholine content. The effects of varying HDL phospholipid
      composition on SR-BI-mediated free cholesterol flux were not correlated with
      changes in either the K(d) or B(max) values for high affinity binding to SR-BI.
      We conclude that SR-BI-mediated free cholesterol flux is highly sensitive to HDL
      phospholipid composition. Thus, factors that regulate cellular SR-BI expression
      and the local modification of HDL phospholipid composition will have a large
      impact on reverse cholesterol transport.

PMID- 10964931
TI  - Platelet-derived growth factor receptor beta and vascular endothelial growth
      factor receptor 2 bind to the beta 3 integrin through its extracellular domain.
AB  - Integrin-mediated cell attachment and growth factor stimulation often act
      synergistically on cell proliferation, differentiation, migration, and survival.
      Some of these synergistic effects depend on the physical interaction of integrins
      with growth factor receptors. Here we examine the nature of the physical
      interaction between the alpha(v)beta(3) integrin and two receptor tyrosine
      kinases (RTKs), the platelet-derived growth factor receptor beta (PDGF-Rbeta) and
      the vascular endothelial growth factor receptor 2 (VEGF-R2, also known as KDR and
      flk-1). Both of these RTKs associate with the alpha(v)beta(3) integrin but do not
      associate with beta(1) integrins. Furthermore, growth factor stimulation of these
      RTKs promotes increased cell proliferation and migration when cells are attached
      to the alpha(v)beta(3) ligand, vitronectin. We show that alpha(v)beta(3) in which
      the beta(3) cytoplasmic domain is deleted or replaced with the beta(1)
      cytoplasmic domain coimmunoprecipitates with PDGF-Rbeta and VEGF-R2. The beta(3)
      extracellular domain alone was sufficient for the PDGF-Rbeta association whereas
      the VEGF-R2 association required the presence of the alpha(v) subunit. Activation
      of the RTKs by their ligands was not required for them to associate with the
      integrin. Cell migration to PDGF was enhanced in the cells transfected with the
      chimeric subunit containing the beta(3) extracellular domain but not when that
      domain came from the beta(1) subunit. These results show that the interactions
      that lead to the association of the alpha(v)beta(3) integrin with PDGF-Rbeta and
      VEGF-R2 and enhancement of RTK activity take place outside the cell.

PMID- 10964932
TI  - HeLp, a heme lipoprotein from the hemolymph of the cattle tick, Boophilus
      microplus.
AB  - The main protein of the hemolymph of the cattle tick Boophilus microplus has been
      isolated and shown to be a heme lipoprotein (HeLp). HeLp has an apparent
      molecular mass of 354,000 and contains two apoproteins (103 and 92 kDa) found in
      equal amounts. HeLp presents a pI of 5.8 and a density of 1.28 g/ml and contains
      33% lipids, containing both neutral lipids and phospholipids, and 3% of sugars. A
      remarkable feature of HeLp is the abundance of cholesterol ester (35% of total
      lipids), a lipid not previously reported in invertebrate lipoproteins. Western
      blot analysis showed HeLp in hemolymph from adult females and males, but not in
      eggs. Although HeLp contains 2 heme molecules, it is capable of binding 6
      additional molecules of heme. Boophilus feeds large amount of blood, and we
      recently showed that this tick is unable to perform de novo synthesis of heme
      (Braz, G. R. C., Coelho, H. S. L., Masuda, H., and Oliveira, P. L. (1999) Curr.
      Biol. 9, 703-706). Injection of tick females with (55)Fe-labeled heme-HeLp
      indicated that this protein transports heme from hemolymph to tissues. HeLp is
      suggested to be an essential adaptation to the loss of the heme synthesis
      pathway.

PMID- 10964933
TI  - Identification of a novel gp130-responsive site in the vasoactive intestinal
      peptide cytokine response element.
AB  - The neuropoietic cytokine ciliary neurotrophic factor (CNTF) potently induces
      transcription of the vasoactive intestinal peptide (VIP) gene through a 180-base
      pair (bp) cytokine response element (CyRE) in the VIP promoter. We have
      previously shown that CNTF induction of STAT and AP-1 protein binding within the
      CyRE is necessary to mediate CNTF induction of VIP gene transcription. We now
      show that a third, previously uncharacterized site at the 3'-end of the CyRE is
      also critical to CNTF induction of CyRE transcription. A 4-bp mutation in this 3'
      region reduced CNTF-mediated induction of transcription approximately 80%.
      Whereas mutations in both the STAT and AP-1 sites substantially reduced CNTF
      induction of transcription, mutations in these sites together with the novel 3'
      site completely abolished the ability of CNTF to induce CyRE-mediated
      transcription. Gel shift analysis indicated that a complex in neuroblastoma cells
      bound specifically to this 3'-site. This complex was not altered by CNTF
      treatment. Mutations in an 8-bp sequence (TTACTGGA) eliminated binding of this
      protein complex and markedly reduced transcriptional activation of the CyRE by
      CNTF. Thus, we have identified a protein complex binding to a novel DNA sequence
      that is necessary for full CNTF induction of VIP gene transcription.

PMID- 10964934
TI  - The role of the hinge region of the luteinizing hormone receptor in hormone
      interaction and signal generation.
AB  - Luteinizing hormone receptor, a G protein-coupled receptor, consists of two
      halves, the N-terminal extracellular hormone binding domain (exodomain) and the C
      terminal membrane-associated, signal-generating domain (endodomain). The
      exodomain has seven to nine Leu-rich repeats, which are generally thought to form
      a 1/3 donut-like structure and interact with human choriogonadotropin (hCG). The
      resulting hCG-exodomain complex adjusts the structure and its association with
      the endodomain, which results in signal generation in the endodomain. It is
      unclear whether the rigid 1/3 donut structure could provide the agility and
      versatility of this dynamic action. In addition, there is no clue as to where the
      endodomain contact point (the signal modulator) in the exodomain is. To address
      these issues, the exodomain was examined by Ala scan and multiple substitutions,
      while receptor peptides were used for photoaffinity labeling and affinity cross
      linking. Our results show that the C-flanking sequence (hinge region), Thr(250)
      Gln(268), of the Leu-rich repeats (LRRs) specifically interacts with hCG,
      preferentially hCGalpha. This interaction is inhibited by exoloop 2 of the
      endodomain but not by exoloops 1 and 3, suggesting an intimate relationship
      between Thr(250)-Gln(268), exoloop 2, and hCG. Taken together, our observations
      in this article suggest a new paradigm that the LRRs contact the front of hCG,
      while both flanking regions of the LRRs interact with the sides of hCG. This
      would trap hCG in the 1/3 donut structure of the LRRs and enhance the binding
      affinity. In addition, mutations of conserved Ser(255) in the sequence can
      constitutively activate the receptor. This provides a clue for the signal
      modulator in the exodomain. In contrast, a phenyl or phenolic group is necessary
      at conserved Tyr(253) for targeting the receptor to the surface.

PMID- 10964935
TI  - Escherichia coli soft metal ion-translocating ATPases.

PMID- 10964937
TI  - Analysis of presynaptic Ca2+ influx and transmitter release kinetics during
      facilitation at the inhibitor of the crayfish neuromuscular junction.
AB  - The inhibitory synapse of the crayfish neuromuscular junction was used to examine
      mechanisms underlying the F2 component of synaptic facilitation. Because previous
      studies have shown accelerated transmitter release during facilitation, we
      examined whether an activity-dependent plasticity in I(Ca) could underlie this
      acceleration. We established that fluorescent transients generated by Magnesium
      Green can resolve small differences in presynaptic Ca(2+) influx that correlate
      with changes in IPSC waveform. However, there was no change in Ca(2+) transients
      associated with the accelerated release. Analyzing the initial rise of IPSC and
      the duration of the presynaptic spike yielded a depolarization-release coupling
      plot that captures the impact of spike waveform on the initial rate of release.
      We conclude that accelerated release during F2 facilitation cannot be attributed
      to plasticity of I(Ca) or modulation of spike waveform. Kinetic analysis showed a
      reduction in synaptic delay during facilitation only when broad action potentials
      were used. In unfacilitated release, synaptic delay increased as spike duration
      lengthened. We propose that small single Ca(2+) channel currents during the
      plateau phase of broad action potentials raise local Ca(2+) concentration only
      enough to fill a high-affinity site. Occupation of this site in itself, or events
      downstream, would convert a vesicle from control to facilitated state. If the
      conversion were a slow process, it could explain the changes in synaptic delay
      reported here. This hypothesis can also account for a number of observations
      related to Ca(2+) cooperativity and synaptic facilitation.

PMID- 10964936
TI  - Both protein kinase A and mitogen-activated protein kinase are required in the
      amygdala for the macromolecular synthesis-dependent late phase of long-term
      potentiation.
AB  - The lateral amygdala (LA) is thought to be critical for the specific acquisition
      of conditioned fear, and the emotionally charged memories related to fear are
      thought to require a form of synaptic plasticity related to long-term
      potentiation (LTP). Is LTP in the lateral amygdala enduring, and, if so, does it
      require gene expression and the synthesis of new protein? Using brain slices, we
      have examined the molecular-signaling pathway of LTP in the cortico-amygdala and
      the thalamo-amygdala pathways. We find that a single high-frequency train of
      stimuli induces a transient LTP (E-LTP); by contrast, five repeated high
      frequency trains induce an enduring late phase of LTP (L-LTP), which is dependent
      on gene expression and on new protein synthesis. In both pathways the late phase
      of LTP is mediated by protein kinase A (PKA) and mitogen-activated protein kinase
      (MAPK). Application of the adenylyl cyclase activator forskolin induced L-LTP in
      both pathways, and this potentiation is blocked by inhibitors of protein
      synthesis. The late phase of LTP also is modulated importantly by beta-adrenergic
      agonists. An inhibitor of beta-adrenergic receptors blocks L-LTP; conversely,
      application of a beta-adrenergic agonist induces the L-LTP. Immunocytochemical
      studies show that both repeated tetanization and application of forskolin
      stimulate the phosphorylation of cAMP response element-binding proteins (CREB) in
      cells of the lateral nucleus of the amygdala. These results suggest that PKA and
      MAPK are critical for the expression of a persistent phase of LTP in the lateral
      amygdala and that this late component requires the synthesis of new protein and
      mRNA.

PMID- 10964938
TI  - Cbln3, a novel member of the precerebellin family that binds specifically to
      Cbln1.
AB  - Precerebellin (Cbln1) is the precursor of the brain-specific hexadecapeptide
      cerebellin. Although cerebellin has properties of a conventional neuropeptide,
      its function is controversial because Cbln1 has structural features
      characteristic of circulating atypical collagens. Cbln1 is related to the three
      subunits of the complement C1q complex. Therefore, we hypothesized that Cbln1
      participated in analogous heteromeric complexes with precerebellin-related
      proteins. Using LexA-Cbln1 as bait in a yeast two-hybrid screen, we isolated a
      cDNA encoding a novel Cbln1-related protein, designated Cbln3. The gene encoding
      cbln3 had the same intron-exon structure as cbln1 but mapped to a different mouse
      chromosome (14). The deduced amino acid sequence of Cbln3 was 55% identical to
      Cbln1 and also contained a C1q signature domain and signal sequence for
      secretion. In addition to binding avidly to Cbln3, Cbln1 also formed homomeric
      complexes. In contrast, Cbln3 homomeric association was weak. These interactions
      exhibited specificity because C1qB bound to neither Cbln1 nor Cbln3. Like cbln1,
      cbln3 was expressed in the cerebellum and dorsal cochlear nucleus in which it was
      detected in granule neurons. Because Cbln1 and Cbln3 are coexpressed in the brain
      and interact avidly, they may function as a secreted heteromeric complex in vivo.

PMID- 10964939
TI  - Neurotrophins induce death of hippocampal neurons via the p75 receptor.
AB  - Nerve growth factor (NGF) and related neurotrophins influence neuronal survival
      and differentiation via interactions with the trk family of receptors. Recent
      studies have demonstrated that neurotrophins may also induce cell death via the
      p75 receptor. The importance and generality of neurotrophin-induced death in the
      brain have not been defined but may play a critical role during development and
      in disease-associated neuronal death. Here we demonstrate for the first time that
      all four members of the neurotrophin family directly elicit the death of
      hippocampal neurons via the p75 receptor. The hippocampus is a complex structure
      with many different neuronal subpopulations, and signals that influence neuronal
      death during development may have a critical impact on the mature function of
      this structure. In these studies we show that each neurotrophin causes the death
      of hippocampal neurons expressing p75 but lacking the cognate trk receptor.
      Neurotrophin-induced neuronal death is mediated by activation of Jun kinase.
      These studies demonstrate that neurotrophins can regulate death as well as
      survival of CNS neurons.

PMID- 10964940
TI  - The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal
      effects of inhalation anesthetics.
AB  - Despite widespread use of volatile general anesthetics for well over a century,
      the mechanisms by which they alter specific CNS functions remain unclear. Here,
      we present evidence implicating the two-pore domain, pH-sensitive TASK-1 channel
      as a target for specific, clinically important anesthetic effects in mammalian
      neurons. In rat somatic motoneurons and locus coeruleus cells, two populations of
      neurons that express TASK-1 mRNA, inhalation anesthetics activated a neuronal
      K(+) conductance, causing membrane hyperpolarization and suppressing action
      potential discharge. These membrane effects occurred at clinically relevant
      anesthetic levels, with precisely the steep concentration dependence expected for
      anesthetic effects of these compounds. The native neuronal K(+) current displayed
      voltage- and time-dependent properties that were identical to those mediated by
      the open-rectifier TASK-1 channel. Moreover, the neuronal K(+) channel and
      heterologously expressed TASK-1 were similarly modulated by extracellular pH. The
      decreased cellular excitability associated with TASK-1 activation in these cell
      groups probably accounts for specific CNS effects of anesthetics: in motoneurons,
      it likely contributes to anesthetic-induced immobilization, whereas in the locus
      coeruleus, it may support analgesic and hypnotic actions attributed to inhibition
      of those neurons.

PMID- 10964941
TI  - Neurotrophic actions of a novel molluscan epidermal growth factor.
AB  - The mammalian epidermal growth factor (EGF) is expressed in the developing and
      adult CNS, and it has been implicated in the control of cell proliferation,
      differentiation, and neurotrophic events. Despite extensive evolutionary
      conservation of the EGF motif in a range of different types of proteins, secreted
      EGF homologs with neurotrophic actions have not been reported in invertebrates.
      In this study, we present a novel member of the family of EGF-like growth
      factors, an EGF homolog from the mollusc Lymnaea stagnalis (L-EGF), and we
      demonstrate that this protein has neurotrophic activity. Purified L-EGF is a 43
      residue peptide and retains the typical structural characteristics of the EGF
      motif. The L-EGF cDNA reveals a unique precursor organization. In contrast to the
      multidomain mammalian EGFs, it consists of only two domains, a signal peptide and
      a single EGF motif. Conspicuously, the L-EGF precursor lacks a transmembrane
      domain, setting it apart from all other members of the EGF-family. L-EGF mRNA is
      expressed throughout embryonic development, in the juvenile CNS, but not in the
      normal adult CNS. However, expression in the adult CNS is upregulated after
      injury, suggesting a role of L-EGF in repair functions. This notion is supported
      by the observation that L-EGF evokes neurite outgrowth in specific adult Lymnaea
      neurons in vitro, which could be inhibited by an EGF receptor tyrosine kinase
      inhibitor. In conclusion, our findings further substantiate the notion that the
      EGF family has an early phylogenetic origin, and our data support a neurotrophic
      role for L-EGF during development and injury repair.

PMID- 10964942
TI  - Subcellular localization of wild-type and Parkinson's disease-associated mutant
      alpha -synuclein in human and transgenic mouse brain.
AB  - Mutations in the alpha-synuclein (alphaSYN) gene are associated with rare cases
      of familial Parkinson's disease, and alphaSYN is a major component of Lewy bodies
      and Lewy neurites. Here we have investigated the localization of wild-type and
      mutant [A30P]alphaSYN as well as betaSYN at the cellular and subcellular level.
      Our direct comparative study demonstrates extensive synaptic colocalization of
      alphaSYN and betaSYN in human and mouse brain. In a sucrose gradient equilibrium
      centrifugation assay, a portion of betaSYN floated into lower density fractions,
      which also contained the synaptic vesicle marker synaptophysin. Likewise, wild
      type and [A30P]alphaSYN were found in floating fractions. Subcellular
      fractionation of mouse brain revealed that both alphaSYN and betaSYN were present
      in synaptosomes. In contrast to synaptophysin, betaSYN and alphaSYN were
      recovered from the soluble fraction upon lysis of the synaptosomes. Synaptic
      colocalization of alphaSYN and betaSYN was directly visualized by confocal
      microscopy of double-stained human brain sections. The Parkinson's disease
      associated human mutant [A30P]alphaSYN was found to colocalize with betaSYN and
      synaptophysin in synapses of transgenic mouse brain. However, in addition to
      their normal presynaptic localization, transgenic wild-type and [A30P]alphaSYN
      abnormally accumulated in neuronal cell bodies and neurites throughout the brain.
      Thus, mutant [A30P]alphaSYN does not fail to be transported to synapses, but its
      transgenic overexpression apparently leads to abnormal cellular accumulations.

PMID- 10964943
TI  - KIF5C, a novel neuronal kinesin enriched in motor neurons.
AB  - Kinesin superfamily proteins (KIFs) are the molecular motors conveying cargos
      along microtubules. KIF5s, the heavy chains of conventional kinesin (KHC), are
      originally identified members of KIFs, and neuronal KIF5A and ubiquitous KIF5B
      have been identified so far. In the present work, we cloned a novel member of
      KIF5, KIF5C, and generated specific antibodies against three KIF5s to investigate
      their distribution and functions. KIF5A showed pan-neuronal distribution in the
      nervous system. KIF5B showed a glial cell distribution pattern in general;
      however, interestingly, its expression was strongly upregulated in axon
      elongating neurons, such as olfactory primary neurons and mossy fibers. KIF5C was
      also a neuronal KIF5 like KIF5A but was highly expressed in lower motor neurons
      in 2-week-old or older mice, suggesting its important roles in the maintenance of
      motor neurons rather than in their formation, such as axonal elongation. Because
      a large part of KIF5s in adult motor neurons were expected to be KIF5C, we
      generated mice lacking the kif5C gene to investigate the functions of KIF5C in
      neurons in living animals. The mutant mice showed smaller brain size but were
      viable and did not show gross changes in the nervous system. Closer examinations
      revealed the relative loss of motor neurons to sensory neurons. Because three
      KIF5s showed high similarity in the amino acid sequence, could rescue the KIF5B
      mutant cells, and could form heterodimers, we think that there are functional
      redundancy among the three KIF5s and that KIF5A and KIF5B prevented the KIF5C
      null mice from the severe phenotype.

PMID- 10964944
TI  - CaMKIIalpha 3' untranslated region-directed mRNA translocation in living neurons:
      visualization by GFP linkage.
AB  - The CaMKIIalpha mRNA extends into distal hippocampal dendrites, and the 3'
      untranslated region (3'UTR) is sufficient to mediate this localization. We
      labeled the 3'UTR of the CaMKIIalpha mRNA in hippocampal cultures by using a
      green fluorescent protein (GFP)/MS2 bacteriophage tagging system. The CaMKIIalpha
      3'UTR formed discrete granules throughout the dendrites of transfected cells. The
      identity of the fluorescent granules was verified by in situ hybridization. Over
      30 min time periods these granules redistributed without a net increase in
      granule number; with depolarization there is a tendency toward increased numbers
      of granules in the dendrites. These observations suggest that finer time
      resolution of granule motility might reveal changes in the motility
      characteristics of granules after depolarization. So that motile granules could
      be tracked, shorter periods of observation were required. The movements of motile
      granules can be categorized as oscillatory, unidirectional anterograde, or
      unidirectional retrograde. Colocalization of CaMKIIalpha 3'UTR granules and
      synapses suggested that oscillatory movements allowed the granules to sample
      several local synapses. Neuronal depolarization increased the number of granules
      in the anterograde motile pool. Based on the time frame over which the granule
      number increased, the translocation of granules may serve to prepare the dendrite
      for mounting an adequate local translation response to future stimuli. Although
      the resident pool of granules can respond to signals that induce local
      translation, the number of granules in a dendrite might reflect its activation
      history.

PMID- 10964945
TI  - The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta
      subunit-specific enhanced activation of P/Q-type calcium channels in Xenopus
      oocytes.
AB  - Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited degenerative
      disorder of the cerebellum characterized by nearly selective and progressive
      death of Purkinje cells. The underlying mutation in SCA6 consists of an expansion
      of a trinucleotide CAG repeat in the 3' region of the gene, CACNA1A, encoding the
      alpha(1A) subunit of the neuronal P/Q-type voltage-gated calcium channel.
      Although it is known that this mutation results in an expanded tract of glutamine
      residues in some alpha(1A) splice forms, the distribution of these splice forms
      and the role of this mutation in the highly selective Purkinje cell degeneration
      seen in SCA6 have yet to be elucidated. Using specific antisera we demonstrate
      that the pathological expansion in SCA6 can potentially be expressed in multiple
      isoforms of the alpha(1A) subunit, and that these isoforms are abundantly
      expressed in the cerebellum, particularly in the Purkinje cell bodies and
      dendrites. Using alpha(1A) subunit chimeras expressing SCA6 mutations, we show
      that the SCA6 polyglutamine expansion shifts the voltage dependence of channel
      activation and rate of inactivation only when expressed with beta(4) subunits and
      impairs normal G-protein regulation of P/Q channels. These findings suggest the
      possibility that SCA6 is a channelopathy, and that the underlying mutation in
      SCA6 causes Purkinje cell degeneration through excessive entry of calcium ions.

PMID- 10964946
TI  - NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple
      sclerosis lesions.
AB  - Multiple sclerosis (MS) is characterized by multifocal loss of myelin,
      oligodendrocytes, and axons. Potential MS therapies include enhancement of
      remyelination by transplantation or manipulation of endogenous oligodendrocyte
      progenitor cells. Characteristics of endogenous oligodendrocyte progenitors in
      normal human brain and in MS lesions have not been studied extensively. This
      report describes the distribution of cells in sections from normal adult human
      brain and MS lesions by using antibodies directed against NG2, an integral
      membrane chondroitin sulfate proteoglycan expressed by oligodendrocyte progenitor
      cells. Stellate-shaped NG2-positive cells were detected in the white and gray
      matter of normal adult human brain and appeared as abundant as, but distinct
      from, astrocytes, oligodendrocytes, and microglia. Stellate-shaped or elongated
      NG2-positive cells also were detected in chronic MS lesions. A subpopulation of
      the elongated NG2-positive cells expressed the putative apoptotic signaling
      molecule p75(NTR). TUNEL-positive cells in three active, nine chronic active, and
      four chronic inactive lesions, however, were p75(NTR)-negative. These studies
      identify cells with phenotypic markers of endogenous oligodendrocyte progenitors
      in the mature human CNS and suggest that functional subpopulations of NG2
      positive cells exist in MS lesions. Endogenous oligodendrocyte progenitor cells
      may represent a viable target for future therapies intended to enhance
      remyelination in MS patients.

PMID- 10964947
TI  - Selective activation of mGlu4 metabotropic glutamate receptors is protective
      against excitotoxic neuronal death.
AB  - Activation of group III metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7,
      and mGluR8) has been established to be neuroprotective in vitro and in vivo. To
      disclose the identity of the receptor subtype(s) that exert(s) the protective
      effect, we have used group III agonists in combination with mGluR4 subtype
      deficient mice (-/-). In cortical cultures prepared from wild-type (+/+) mice and
      exposed to a toxic pulse of NMDA, the selective group III agonist (+)-4
      phosphonophenylglycine [(+)-PPG] reversed excitotoxicity with an EC(50) value of
      4.9 microm, whereas its enantiomer (-)-PPG was inactive. This correlated closely
      with the potency of (+)-PPG in activating recombinant mGluR4a. In cortical
      neurons from -/- mice, (+)-PPG showed no protection against the NMDA insult up to
      300 microm, whereas group I/II mGluR ligands still retained their protective
      activity. Classical group III agonists (l-2-amino-4-phosphonobutyrate and l
      serine-O-phosphate) were also substantially neuroprotective against NMDA toxicity
      in +/+ and heterozygous (+/-) cultures but were inactive in -/- cultures.
      Interestingly, -/- cultures were more vulnerable to low concentrations of NMDA
      and showed higher extracellular glutamate levels compared with +/+ cultures. We
      have also examined neurodegeneration induced by intrastriatal infusion of NMDA in
      wild-type or mGluR4-deficient mice. Low doses of (R,S)-PPG (10 nmol/0.5 microl)
      substantially reduced NMDA toxicity in +/+ mice but were ineffective in -/- mice.
      Higher doses of (R,S)-PPG were neuroprotective in both strains of animals.
      Finally, microdialysis studies showed that intrastriatal infusion of NMDA
      increased extracellular glutamate levels to a greater extent in -/- than in +/+
      mice, supporting the hypothesis that the mGluR4 subtype is necessary for the
      maintenance of the homeostasis of extracellular glutamate levels.

PMID- 10964948
TI  - Passive or active immunization with myelin basic protein promotes recovery from
      spinal cord contusion.
AB  - Partial injury to the spinal cord can propagate itself, sometimes leading to
      paralysis attributable to degeneration of initially undamaged neurons. We
      demonstrated recently that autoimmune T cells directed against the CNS antigen
      myelin basic protein (MBP) reduce degeneration after optic nerve crush injury in
      rats. Here we show that not only transfer of T cells but also active immunization
      with MBP promotes recovery from spinal cord injury. Anesthetized adult Lewis rats
      subjected to spinal cord contusion at T7 or T9, using the New York University
      impactor, were injected systemically with anti-MBP T cells at the time of
      contusion or 1 week later. Another group of rats was immunized, 1 week before
      contusion, with MBP emulsified in incomplete Freund's adjuvant (IFA). Functional
      recovery was assessed in a randomized, double-blinded manner, using the open
      field behavioral test of Basso, Beattie, and Bresnahan. The functional outcome of
      contusion at T7 differed from that at T9 (2.9+/-0.4, n = 25, compared with 8.3+/
      0.4, n = 12; p<0.003). In both cases, a single T cell treatment resulted in
      significantly better recovery than that observed in control rats treated with T
      cells directed against the nonself antigen ovalbumin. Delayed treatment with T
      cells (1 week after contusion) resulted in significantly better recovery (7.0+/
      1; n = 6) than that observed in control rats treated with PBS (2.0+/-0.8; n = 6;
      p<0.01; nonparametric ANOVA). Rats immunized with MBP obtained a recovery score
      of 6.1+/-0.8 (n = 6) compared with a score of 3.0+/-0.8 (n = 5; p<0.05) in
      control rats injected with PBS in IFA. Morphometric analysis, immunohistochemical
      staining, and diffusion anisotropy magnetic resonance imaging showed that the
      behavioral outcome was correlated with tissue preservation. The results suggest
      that T cell-mediated immune activity, achieved by either adoptive transfer or
      active immunization, enhances recovery from spinal cord injury by conferring
      effective neuroprotection. The autoimmune T cells, once reactivated at the lesion
      site through recognition of their specific antigen, are a potential source of
      various protective factors whose production is locally regulated.

PMID- 10964949
TI  - Phenotypic characterization of an alpha 4 neuronal nicotinic acetylcholine
      receptor subunit knock-out mouse.
AB  - Neuronal nicotinic acetylcholine receptors (nAChR) are present in high abundance
      in the nervous system (Decker et al., 1995). There are a large number of subunits
      expressed in the brain that combine to form multimeric functional receptors. We
      have generated an alpha(4) nAChR subunit knock-out line and focus on defining the
      behavioral role of this receptor subunit. Homozygous mutant mice (Mt) are normal
      in size, fertility, and home-cage behavior. Spontaneous unconditioned motor
      behavior revealed an ethogram characterized by significant increases in several
      topographies of exploratory behavior in Mt relative to wild-type mice (Wt) over
      the course of habituation to a novel environment. Furthermore, the behavior of Mt
      in the elevated plus-maze assay was consistent with increased basal levels of
      anxiety. In response to nicotine, Wt exhibited early reductions in a number of
      behavioral topographies, under both unhabituated and habituated conditions;
      conversely, heightened levels of behavioral topographies in Mt were reduced by
      nicotine in the late phase of the unhabituated condition. Ligand autoradiography
      confirmed the lack of high-affinity binding to radiolabeled nicotine, cytisine,
      and epibatidine in the thalamus, cortex, and caudate putamen, although binding to
      a number of discrete nuclei remained. The study confirms the pivotal role played
      by the alpha(4) nAChR subunit in the modulation of a number of constituents of
      the normal mouse ethogram and in anxiety as assessed using the plus-maze.
      Furthermore, the response of Mt to nicotine administration suggests that
      persistent nicotine binding sites in the habenulo-interpeduncular system are
      sufficient to modulate motor activity in actively exploring mice.

PMID- 10964950
TI  - Arsenite-induced apoptosis in cortical neurons is mediated by c-Jun N-terminal
      protein kinase 3 and p38 mitogen-activated protein kinase.
AB  - c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase
      are activated by stress and are implicated in regulation of apoptosis in several
      tissues. However, their contribution to stress-induced apoptosis in CNS neurons
      is not well defined. Here we investigated the role of JNK and p38 in cortical
      neuron apoptosis caused by sodium arsenite treatment. Sodium arsenite is an
      environmental toxicant that causes developmental defects in the CNS. Treatment of
      cortical neurons with sodium arsenite activated p38 and JNK3 but not JNK1 or
      JNK2. It also induced c-Jun phosphorylation. Furthermore, sodium arsenite induced
      cortical neuron apoptosis. This apoptosis was attenuated by SB203580, an
      inhibitor of p38, and by CEP-1347, an inhibitor of JNK activation. Expression of
      dominant-interfering mutants of the JNK or p38 pathways inhibited apoptosis
      induced by arsenite, whereas expression of constitutive active mutants for either
      pathway induced apoptosis. Moreover, the caspase inhibitor zVAD
      fluoromethylketone as well as expression of bcl-2 or bcl-xL inhibited cortical
      neuron apoptosis induced by arsenite or by constitutive activation of JNK or p38.
      These data indicate that both JNK and p38 contribute to arsenite-induced
      apoptosis in primary CNS neurons, and this apoptosis requires the bcl-2-caspase
      pathway. This is the first evidence that a specific JNK isoform is differentially
      activated by stress and contributes to neuronal apoptosis.

PMID- 10964951
TI  - Aging increased amyloid peptide and caused amyloid plaques in brain of old
      APP/V717I transgenic mice by a different mechanism than mutant presenilin1.
AB  - Aging of transgenic mice that overexpress the London mutant of amyloid precursor
      protein (APP/V717I) (Moechars et al., 1999a) was now demonstrated not to affect
      the normalized levels of alpha- or beta-cleaved secreted APP nor of the beta-C
      terminal stubs. This indicated that aging did not markedly disturb either alpha-
      or beta-secretase cleavage of APP and failed to explain the origin of the massive
      amounts of amyloid peptides Abeta40 and Abeta42, soluble and precipitated as
      amyloid plaques in the brain of old APP/V717I transgenic mice. We tested the
      hypothesis that aging acted on presenilin1 (PS1) to affect gamma-secretase
      mediated production of amyloid peptides by comparing aged APP/V717I transgenic
      mice to double transgenic mice coexpressing human PS1 and APP/V717I. In double
      transgenic mice with mutant (A246E) but not wild-type human PS1, brain amyloid
      peptide levels increased and resulted in amyloid plaques when the mice were only
      6-9 months old, much earlier than in APP/V717I transgenic mice (12-15 months
      old). Mutant PS1 increased mainly brain Abeta42 levels, whereas in aged APP/V717I
      transgenic mice, both Abeta42 and Abeta40 increased. This resulted in a dramatic
      difference in the Abeta42/Abeta40 ratio of precipitated or plaque-associated
      amyloid peptides, i.e., 3.11+/-0.22 in double APP/V717I x PS1/A246E transgenic
      mice compared with 0.43 +/- 0.07 in aged APP/V717I transgenic mice, and
      demonstrated a clear difference between the effect of aging and the effect of the
      insertion of a mutant PS1 transgene. In conclusion, we demonstrate that aging did
      not favor amyloidogenic over nonamyloidogenic processing of APP, nor did it exert
      a mutant PS1-like effect on gamma-secretase. Therefore, the data are interpreted
      to suggest that parenchymal and vascular accumulation of amyloid in aging brain
      resulted from failure to clear the amyloid peptides rather than from increased
      production.

PMID- 10964952
TI  - Impaired synaptic plasticity and cAMP response element-binding protein activation
      in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice.
AB  - The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key
      effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene
      disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP
      responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB
      dependent gene expression. They were also deficient in two forms of synaptic
      plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late
      phase of long-term depression in cerebellar Purkinje neurons. However, despite
      impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious
      deficits in spatial learning and memory. These results support an important role
      for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic
      plasticity and suggest that the contribution of other signaling pathways may
      spare spatial memory of CaMKIV/Gr-deficient mice.

PMID- 10964954
TI  - Cerebral ischemia and seizures induce tyrosine phosphorylation of PYK2 in neurons
      and microglial cells.
AB  - The nonreceptor tyrosine kinase PYK2 represents a stress-sensitive mediator of c
      Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK) signaling
      pathways in many cell types. In the present study, we assessed the tyrosine
      phosphorylation of PYK2 under normal and pathological conditions in the CNS. We
      generated a polyclonal antibody that selectively recognizes tyrosine
      phosphorylated PYK2 at its major autophosphorylation site. By using this
      antibody, we demonstrate that the phosphorylation profile of PYK2 after focal
      cerebral ischemia is biphasic. The first phase occurs within 1 hr, when most of
      the phospho-PYK2 immunoreactivity was observed in cortical neurons, whereas 24-72
      hr after ischemia, a striking induction of phospho-PYK2 immunoreactivity was
      evident in microglia around the necrotic infarcted area. Double-immunostaining
      analysis using both anti-phospho-PYK2 antibody and antibody against the double
      phosphorylated active form of p38MAPK revealed that the two phosphorylated
      protein kinases exhibit strikingly similar distribution patterns after ischemia.
      A short time after ischemia, phosphorylation of p38MAPK was evident in the
      cortical neurons as demonstrated by both immunohistochemistry and immunoblotting
      analysis, whereas 24-72 hr after ischemia, phospho-p38MAPK was found in activated
      microglia and colocalized with phospho-PYK2. In contrast to cortical neurons,
      basal phospho-PYK2 immunoreactivity was observed in hippocampal pyramidal
      neurons, which was markedly decreased after kainate acid-induced status
      epilepticus. However, 24 hr after the epileptic onset, a pronounced upregulation
      of PYK2 and phospho-PYK2 immunoreactivities was evident in microglial cells, as
      demonstrated by double-immunostaining with the microglial marker OX42. These
      results provide, for the first time, in situ localization of tyrosine
      phosphorylated PYK2 in neuronal stress pathways in the adult rat brain and are
      consistent with the role of PYK2 as an upstream regulator of p38MAPK signaling
      cascades in response to stress signals.

PMID- 10964953
TI  - Induction of IkappaBalpha mRNA expression in the brain by glucocorticoids: a
      negative feedback mechanism for immune-to-brain signaling.
AB  - Peripheral injection of bacterial endotoxin lipopolysaccharide (LPS) induces
      brain mRNA expression of the proinflammatory cytokines interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha and the cytokine-responsive immediate
      early gene IkappaBalpha. Peripheral LPS also increases levels of plasma
      glucocorticoids. Whether the induction of IkappaBalpha mRNA in the brain after
      peripheral LPS injection is caused by the feedback action of glucocorticoids has
      not been determined. In this study, we examined the mRNA expression of
      IkappaBalpha and IL-1beta in the rat brain by in situ hybridization
      histochemistry. Injection of the glucocorticoid agonist dexamethasone induced
      IkappaBalpha mRNA expression in the brain in a pattern identical to that of LPS
      injection. LPS but not dexamethasone also induced IL-1beta mRNA expression.
      Pretreatment with dexamethasone 30 min before LPS injection enhanced the
      expression of IkappaBalpha mRNA in the brain in a dose-dependent manner.
      Immobilization of rats for 2 hr (which raises glucocorticoid levels) also induced
      IkappaBalpha mRNA expression without inducing the expression of IL-1beta. Brain
      IkappaBalpha expression induced by peripheral LPS injection was attenuated by
      pretreatment of rats with the glucocorticoid antagonist RU-486. Finally,
      increased expression of IL-1beta mRNA in the brain was observed at 4 hr after
      peripheral LPS injection in adrenalectomized rats compared with sham-operated
      rats. These results reveal that in the brain glucocorticoids selectively induce
      IkappaBalpha mRNA expression, which serves as a negative feedback mechanism for
      peripheral LPS-induced synthesis of proinflammatory cytokines. Such an inhibitory
      control mechanism may be important for preventing prolonged expression of
      proinflammatory cytokines in the brain after peripheral immune challenge.

PMID- 10964955
TI  - Eph receptors and ephrins in the developing chick cerebellum: relationship to
      sagittal patterning and granule cell migration.
AB  - Spatiotemporal expression patterns of six members of the Eph gene family (EphA4,
      EphA3, EphB2, ephrin-B1, ephrin-A2, and ephrin-A5) were characterized
      immunocytochemically at various stages of chick cerebellar development. EphA4
      expression is observed in the cerebellar anlage as early as embryonic day 5 (E5)
      and continues in the posthatch cerebellum. During the early period of cerebellar
      development (E3-E8), complementarity is observed between EphA4 and ephrin-A5
      expression within the cerebellar-isthmal region. By E8, differential expression
      of EphA4 in parasagittal Purkinje cell bands is evident, and the expression
      remains banded in the posthatch cerebellum. Banded expression of the ephrin-A5
      ligand complements EphA4 expression during the middle period (E9-E15). During
      this period, ephrin-A2 and EphA3 are coexpressed in a banded pattern and with
      variable correlation to EphA4. Variability in the banding expression is observed
      for EphA4, EphA3, ephrin-A5, and ephrin-A2 across different lobes, and graded
      complementarity in the expression pattern of EphA3 and ephrin-A5 is observed in
      the external granular layer between the posterior and anterior lobes. Analysis of
      Purkinje cell birth date in correlation with Eph-ephrin expression during the
      middle period reveals that early-born cells express EphA4, whereas late-born
      cells express ephrin-A5. Finally, EphA4 expression domains are respected by
      migrating granule cell ribbons, which express both ephrin-B1 and EphB2. These
      expression patterns suggest multiple roles for the Eph-ephrin system in
      cerebellar development, including demarcation/enforcement of boundaries of the
      cerebellar anlage, formation/maintenance of Purkinje cell compartments, and
      restriction of the early phase of granule cell migration to ribbons.

PMID- 10964956
TI  - Defect of tyrosine hydroxylase-immunoreactive neurons in the brains of mice
      lacking the transcription factor Pax6.
AB  - In the CNS, the lack of the transcription factor Pax6 has been associated with
      early defects in cell proliferation, cell specification, and axonal pathfinding
      of discrete neuronal populations. In this study, we show that Pax6 is expressed
      in discrete catecholaminergic neuronal populations of the developing ventral
      thalamus, hypothalamus, and telencephalon. In mice lacking Pax6, these
      catecholaminergic populations develop abnormally: those in the telencephalon are
      reduced in cell number or absent, whereas those in the ventral thalamus and
      hypothalamus are greatly displaced and densely packed. Catecholaminergic neurons
      of the substantia nigra (SN) and the ventral tegmental area (VTA) do not express
      Pax6 protein. Nevertheless, mice lacking Pax6 display an altered pathfinding of
      SN-VTA projections: instead of following the route of the medial forebrain bundle
      ventrally, most of the SN-VTA projections are deflected dorsorostrally at the
      pretectal-dorsal thalamic transition zone and in the dorsal thalamic alar plate.
      Moreover, some catecholaminergic neurons are displaced dorsally to an ectopic
      location at the pretectal-dorsal thalamic transition zone. Interestingly, from
      the pretectal-dorsal thalamic to the dorsal thalamic-ventral thalamic transition
      zones, mice lacking Pax6 display an ectopic ventral to dorsal expansion of the
      chemorepellant/chemoattractive molecule, Netrin-1. This may be responsible for
      both the altered pathway of catecholaminergic fibers and the ectopic location of
      catecholaminergic neurons in this region.

PMID- 10964958
TI  - Structural and functional alterations of neuromuscular junctions in NCAM
      deficient mice.
AB  - The role of neural cell adhesion molecule (NCAM) in the development and
      maturation of the neuromuscular junction (NMJ) was explored by characterizing
      structurally and functionally NMJs from postnatal day 11 (P11) to P30 +/+, +/-,
      and -/- NCAM null mutant mice. Differences in NCAM levels resulted in alterations
      in the size and shape of NMJs, with -/- NMJs being smaller. Additionally both the
      withdrawal of polyneuronal innervation and the selective accumulation of synaptic
      vesicle protein in the presynaptic terminal were delayed. These observations
      suggest that the bidirectional signaling responsible for these events is impaired
      at -/- NMJs. Functionally, miniature end plate potential size, end plate
      potential size, and quantal content did not differ from that of wild type under
      either normal or low release conditions. However at normal release conditions, -/
      NMJs, unlike +/+ NMJs, lacked paired-pulse facilitation. The most striking
      abnormality was the inability of NCAM null junctions to maintain transmitter
      output with repetitive stimuli. Combined electrophysiological and FM1-43-labeling
      studies suggest that NCAM null junctions are unable either to dock or to mobilize
      a sufficient number of vesicles at high but physiological rates of transmitter
      release. Taken together our observations show that many aspects of transmission
      are normal and, thus, that many presynaptic and postsynaptic molecules have
      assembled properly in the absence of NCAM. However, the fact that NCAM was
      required for specific aspects of transmission, including paired-pulse
      facilitation and reliable transmission with repetitive stimuli, suggests that
      NCAM either is directly involved in these processes or is required for the proper
      organization and/or function of other molecules underlying these processes.

PMID- 10964957
TI  - Laminin expression in adult and developing retinae: evidence of two novel CNS
      laminins.
AB  - Components of the extracellular matrix exert myriad effects on tissues throughout
      the body. In particular, the laminins, a family of heterotrimeric extracellular
      glycoproteins, have been shown to affect tissue development and integrity in such
      diverse organs as the kidney, lung, skin, and nervous system. Of these, we have
      focused on the roles that laminins play in the differentiation and maintenance of
      the nervous system. Here, we examine the expression of all known laminin chains
      within one component of the CNS, the retina. We find seven laminin chains-alpha3,
      alpha4, alpha5, beta2, beta3, gamma2, and gamma3-outside the retinal basement
      membranes. Anatomically, these chains are coexpressed in one or both of two
      locations: the matrix surrounding photoreceptors and the first synaptic layer
      where photoreceptors synapse with retinal interneurons. Biochemically, four of
      these chains are coisolated from retinal extracts in two independent complexes,
      confirming that two novel heterotrimers-alpha4beta2gamma3 and alpha5beta2gamma3
      are present in the retinal matrix. During development, all four of these chains,
      along with components of laminin 5 (the alpha3, beta3, and gamma2 chains) are
      also expressed at sites at which they could exert important effects on
      photoreceptor development. Together, these data suggest the existence of two
      novel laminin heterotrimers in the CNS, which we term here laminin 14 (composed
      of the alpha4, beta2, and gamma3 chains) and laminin 15 (composed of the alpha5,
      beta2, and gamma3 chains), and lead us to hypothesize that these laminins, along
      with laminin 5, may play roles in photoreceptor production, stability, and
      synaptic organization.

PMID- 10964959
TI  - Netrin-G1: a novel glycosyl phosphatidylinositol-linked mammalian netrin that is
      functionally divergent from classical netrins.
AB  - UNC-6/netrins compose a small phylogenetically conserved family of proteins that
      act as axon guidance cues. With a signal sequence trap method, we isolated a cDNA
      encoding a novel member of the UNC-6/netrin family, which we named netrin-G1.
      Unlike classical netrins, netrin-G1 consists of at least six isoforms of which
      five were predominantly anchored to the plasma membrane via glycosyl phosphatidyl
      inositol linkages. Netrin-G1 transcripts were first detected in midbrain and
      hindbrain regions by embryonic day 12 and reached highest levels at perinatal
      stages in various brain regions, including olfactory bulb mitral cells, thalamus,
      and deep cerebellar nuclei. Its expression was primarily restricted to the CNS.
      Interestingly, netrin-G1 proteins did not show appreciable affinity to any netrin
      receptor examined. Unlike netrin-1, a secreted form of netrin-G1 consistently
      failed to attract circumferentially growing axons from the cerebellar plate. Our
      findings suggest that netrin-G1 and its putative receptors have coevolved
      independently from the classical netrins. The expression pattern of netrin-G1 and
      its predicted neuronal membrane localization suggest it may also have novel
      signaling functions in nervous system development.

PMID- 10964960
TI  - Regulation of neurite outgrowth by integrin activation.
AB  - During late-embryonic development, retinal neurons lose the ability to attach and
      extend neurites on the extracellular matrix molecule laminin-1 (LN-1), despite
      the fact that they retain expression of integrin receptors for LN-1. Here we show
      that the developmental loss of responsiveness to LN-1 can be reversed by
      treatments that increase the activation state of integrins. Both extracellular
      application of Mn(2+) (at micromolar concentrations) and viral-mediated neuronal
      expression of a constitutively active form of the ras-related GTPase R-ras (R
      ras(38V)) potently promoted late-embryonic retinal neurite outgrowth on LN-1
      substrata. In both cases, outgrowth was mediated by integrin alpha6beta1 and not
      alpha3beta1, even though these neurons express alpha3beta1 and use it for
      outgrowth on other laminin isoforms, as well as on LN-1 that has been
      proteolytically or conformationally activated (Ivins et al., 1998). Mn(2+)-and to
      a much lesser extent R-ras(38V)-also reversed the developmental loss of retinal
      neuron responsiveness to type IV collagen, by promoting the function of integrin
      alpha1beta1. Interestingly, the responses of other late-embryonic CNS neurons to
      LN-1 were also enhanced by treatments that activate integrin function, but those
      of peripheral nervous system neurons (dorsal root ganglion neurons) were either
      not enhanced (embryonic neurons) or only modestly improved (adult neurons). These
      results suggest that a developmental decline occurs in the activation state of
      neuronal integrins, particularly among CNS neurons. Such a decline may underlie
      some of the intrinsic loss of regenerative ability sustained by CNS neurons
      during development and may be a valid target for therapeutic intervention.

PMID- 10964961
TI  - Compensatory sprouting and impulse rerouting after unilateral pyramidal tract
      lesion in neonatal rats.
AB  - After lesions of the developing mammalian CNS, structural plasticity and
      functional recovery are much more pronounced than in the mature CNS. We
      investigated the anatomical reorganization of the corticofugal projections
      rostral to a unilateral lesion of the corticospinal tract at the level of the
      medullary pyramid (pyramidotomy) and the contribution of this reorganization and
      other descending systems to functional recovery. Two-day-old (P2) and adult rats
      underwent a unilateral pyramidotomy. Three months later the corticofugal
      projections to the red nucleus and the pons were analyzed; a relatively large
      number of corticorubral and corticopontine fibers from the lesioned side had
      crossed the midline and established an additional contralateral innervation of
      the red nucleus and the pons. Such anatomical changes were not seen after adult
      lesions. Intracortical microstimulation of the primary motor cortex with EMG
      recordings of the elbow flexor muscles were used to investigate possible new
      functional connections from the motor cortex of the pyramidotomy side to the
      periphery. In rats lesioned as adults, stimulation of the motor cortex
      ipsilateral to the pyramidotomy never elicited EMG activity. In contrast, in P2
      lesioned rats bilateral forelimb EMGs were found. EMG latencies were comparable
      for the ipsilateral and contralateral responses but were significantly longer
      than in unlesioned animals. Transient inactivation of both red nuclei with the
      GABA receptor agonist muscimol led to a complete loss of these bilateral
      movements. Movements and EMGs reappeared after wash-out of the drug. These
      results suggest an important role of the red nucleus in the reconnection of the
      cortex to the periphery after pyramidotomy.

PMID- 10964963
TI  - Lipopolysaccharide activates specific populations of hypothalamic and brainstem
      neurons that project to the spinal cord.
AB  - Sympathetic preganglionic neurons receive direct, monosynaptic input from a
      series of well defined nuclei in the brainstem and the hypothalamus. These
      premotor cell groups coordinate sympathetic control with ongoing endocrine and
      behavioral response. However, it is not known precisely which populations of
      sympathetic premotor neurons are activated during specific responses, such as
      fever after intravenous lipopolysaccharide (LPS). We used the activation of c-fos
      protein expression in spinally projecting neurons during intravenous LPS fever as
      a model for examining the functional organization of this system. Intravenous LPS
      (5 microg/kg) induced Fos-like immunoreactivity in sympathetic preganglionic
      neurons in the spinal cord as well as several sympathetic premotor nuclei,
      including the paraventricular nucleus of the hypothalamus, rostral and caudal
      levels of the ventrolateral medulla, and the nucleus of the solitary tract. After
      injecting Fluorogold into the intermediolateral column at the T1-L1 spinal
      levels, neurons that were both Fos immunoreactive and retrogradely labeled were
      found only in the dorsal parvicellular division of the paraventricular nucleus in
      the hypothalamus, the rostral ventrolateral medulla (C1 adrenergic cell group),
      and the A5 noradrenergic cell group in the brainstem. The same pattern of double
      labeling was seen from injections at each spinal cord level. These findings
      suggest that only a limited pool of hypothalamo-sympathetic neurons contribute to
      the fever response and that they may do so by contacting specific populations of
      preganglionic neurons that are distributed across a wide range of spinal levels.
      The anatomical specificity of the paraventriculo-spinal projection is thus
      functional rather than topographic.

PMID- 10964962
TI  - Coordinated transitions in neurotransmitter systems for the initiation and
      propagation of spontaneous retinal waves.
AB  - Spontaneous waves of excitation in the developing mammalian retina are mediated,
      to a large extent, by neurotransmission. However, it is unclear how the
      underlying neurotransmitter systems interact with each other to play specific
      roles in the formation of retinal waves at various developmental stages. In
      particular, it is puzzling why the waves maintain a similar propagation pattern
      even after underlying neurotransmitter systems have undergone drastic
      developmental changes. Using Ca(2+) imaging and patch clamp in a whole-mount
      preparation of the developing rabbit retina, we discovered two dramatic and
      coordinated transitions in the excitatory drive for retinal waves: one from a
      nicotinic to a muscarinic system, and the other from a fast cholinergic to a fast
      glutamatergic input. Retinal waves before the age of postnatal day 1 (P1) were
      blocked by nicotinic antagonists, but not by muscarinic or glutamatergic
      antagonists. After P3, however, the spontaneous wave, whose basic spatiotemporal
      pattern remained similar, was completely inhibited by muscarinic or glutamate
      antagonists, but not by nicotinic antagonists. We also found that the muscarinic
      drive, mediated primarily by M1 and M3 receptors, was particularly important for
      wave propagation, whereas the glutamatergic drive seemed more important for local
      excitation. Our results suggest (1) a novel mechanism by which a neurotransmitter
      system changes its functional role via a switch between two completely different
      classes of receptors for the same transmitter, (2) the cholinergic system plays a
      critical role in not only early but also late spontaneous waves, and (3) the
      continued participation of the cholinergic system may provide a network basis for
      the consistency in the overall propagation pattern of spontaneous retinal waves.

PMID- 10964964
TI  - Circuit-specific alterations in hippocampal synaptophysin immunoreactivity
      predict spatial learning impairment in aged rats.
AB  - The present study examined the long-standing concept that changes in hippocampal
      circuitry contribute to age-related learning impairment. Individual differences
      in spatial learning were documented in young and aged Long-Evans rats by using a
      hippocampal-dependent version of the Morris water maze. Postmortem analysis used
      a confocal laser-scanning microscopy method to quantify changes in
      immunofluorescence staining for the presynaptic vesicle glycoprotein,
      synaptophysin (SYN), in the principal relays of hippocampal circuitry.
      Comparisons based on chronological age alone failed to reveal a reliable
      difference in the intensity of SYN staining in any region that was examined. In
      contrast, aged subjects with spatial learning deficits displayed significant
      reductions in SYN immunoreactivity in CA3 lacunosum-moleculare (LM) relative to
      either young controls or age-matched rats with preserved learning. SYN intensity
      values for the latter groups were indistinguishable. In addition, individual
      differences in spatial learning capacity among the aged rats correlated with
      levels of SYN staining selectively in three regions: outer and middle portions of
      the dentate gyrus molecular layer and CA3-LM. The cross-sectional area of SYN
      labeling, by comparison, was not reliably affected in relation cognitive status.
      These findings are the first to demonstrate that a circuit-specific pattern of
      variability in the connectional organization of the hippocampus is coupled to
      individual differences in the cognitive outcome of normal aging. The regional
      specificity of these effects suggests that a decline in the fidelity of input to
      the hippocampus from the entorhinal cortex may play a critical role.

PMID- 10964965
TI  - Coding of border ownership in monkey visual cortex.
AB  - Areas V1 and V2 of the visual cortex have traditionally been conceived as stages
      of local feature representations. We investigated whether neural responses carry
      information about how local features belong to objects. Single-cell activity was
      recorded in areas V1, V2, and V4 of awake behaving monkeys. Displays were used in
      which the same local feature (contrast edge or line) could be presented as part
      of different figures. For example, the same light-dark edge could be the left
      side of a dark square or the right side of a light square. Each display was also
      presented with reversed contrast. We found significant modulation of responses as
      a function of the side of the figure in >50% of neurons of V2 and V4 and in 18%
      of neurons of the top layers of V1. Thus, besides the local contrast border
      information, neurons were found to encode the side to which the border belongs
      ("border ownership coding"). A majority of these neurons coded border ownership
      and the local polarity of luminance-chromaticity contrast. The others were
      insensitive to contrast polarity. Another 20% of the neurons of V2 and V4, and
      48% of top layer V1, coded local contrast polarity, but not border ownership. The
      border ownership-related response differences emerged soon (<25 msec) after the
      response onset. In V2 and V4, the differences were found to be nearly independent
      of figure size up to the limit set by the size of our display (21 degrees ).
      Displays that differed only far outside the conventional receptive field could
      produce markedly different responses. When tested with more complex displays in
      which figure-ground cues were varied, some neurons produced invariant border
      ownership signals, others failed to signal border ownership for some of the
      displays, but neurons that reversed signals were rare. The influence of visual
      stimulation far from the receptive field center indicates mechanisms of global
      context integration. The short latencies and incomplete cue invariance suggest
      that the border-ownership effect is generated within the visual cortex rather
      than projected down from higher levels.

PMID- 10964966
TI  - Prefrontal activation evoked by infrequent target and novel stimuli in a visual
      target detection task: an event-related functional magnetic resonance imaging
      study.
AB  - An event-related functional magnetic resonance imaging study of prefrontal cortex
      was conducted during which subjects performed a visual "oddball" target detection
      task. Exemplars of three stimulus categories were presented at a rate of one per
      1.5 sec for 10 runs, each consisting of 132 trials. Standards were color squares
      of varying sizes that were presented on approximately 92% of trials. Targets were
      color circles of varying sizes presented irregularly on approximately 4% of
      trials. Novels were pictures of everyday objects that were also presented
      irregularly on approximately 4% of trials. Ten subjects participated in two
      separate sessions in which they were required to count mentally or to push a
      button whenever a target appeared. Targets evoked activation within prefrontal
      cortex, primarily within the middle frontal gyri (MFG). This MFG activation did
      not differ as a function of the required response. Novels did not evoke
      significant activity within this region despite evidence from a separate
      behavioral and event-related potential study demonstrating their strong influence
      on processing. In additional imaging sessions with two subjects, the rules were
      reversed to require a button press whenever an object, but not a circle,
      appeared. These former novels now evoked activation in the MFG, but the former
      target circles did not. These experiments indicate that MFG activation is
      reliably evoked by exemplars from arbitrary stimulus categories that are mapped
      by experimental rules onto an arbitrary covert or overt response.

PMID- 10964967
TI  - Molecular underpinnings of motor pattern generation: differential targeting of
      shal and shaker in the pyloric motor system.
AB  - The patterned activity generated by the pyloric circuit in the stomatogastric
      ganglion of the spiny lobster, Panulirus interruptus, results not only from the
      synaptic connectivity between the 14 component neurons but also from differences
      in the intrinsic properties of the neurons. Presumably, differences in the
      complement and distribution of expressed ion channels endow these neurons with
      many of their distinct attributes. Each pyloric cell type possesses a unique,
      modulatable transient potassium current, or A-current (I(A)), that is
      instrumental in determining the output of the network. Two genes encode A
      channels in this system, shaker and shal. We examined the hypothesis that cell
      specific differences in shaker and shal channel distribution contribute to
      diversity among pyloric neurons. We found a stereotypic distribution of channels
      in the cells, such that each channel type could contribute to different aspects
      of the firing properties of a cell. Shal is predominantly found in the
      somatodendritic compartment in which it influences oscillatory behavior and spike
      frequency. Shaker channels are exclusively localized to the membranes of the
      distal axonal compartments and most likely affect distal spike propagation.
      Neither channel is detectably inserted into the preaxonal or proximal portions of
      the axonal membrane. Both channel types are targeted to synaptic contacts at the
      neuromuscular junction. We conclude that the differential targeting of shaker and
      shal to different compartments is conserved among all the pyloric neurons and
      that the channels most likely subserve different functions in the neuron.

PMID- 10964968
TI  - Right-hemisphere dominance for the processing of sound-source lateralization.
AB  - Cortical processing of change in direction of a perceived sound source was
      investigated in 12 human subjects using whole-head magnetoencephalography. The
      German word "da" was presented either with or without 0.7 msec interaural time
      delays to create the impression of right- or left-lateralized or midline sources,
      respectively. Midline stimuli served as standards, and lateralized stimuli served
      as deviants in a mismatch paradigm. Two symmetrically linked dipoles fitted to
      the mismatch fields showed stronger moments in the hemisphere contralateral to
      the side of the deviant. The right dipole displayed equal latencies to both left
      and right deviants, whereas left dipole latencies were longer for ipsilateral
      than contralateral deviants. Frequency analysis between 20-70 Hz and statistical
      probability mapping revealed increased induced gamma-band activity at 53+/-2.5 Hz
      to both types of deviants. Right deviants elicited spectral amplitude
      enhancements in this frequency range, peaking at latencies of 160 and 240 msec.
      These effects were localized bilaterally over the angular gyri and posterior
      temporal regions. Coherence analysis suggested the existence of two separate
      interhemispheric networks. For left-lateralized deviants, both spectral amplitude
      enhancements at 110 and 220 msec and coherence increases were restricted to the
      right hemisphere. In conclusion, both mismatch dipole latencies at the
      supratemporal plane and gamma-band activity in posterior parietotemporal areas
      suggested a right hemisphere engagement in the processing of bidirectional sound
      source shifts. In contrast, left-hemisphere regions responded predominantly to
      contralateral events. These findings may help to elucidate phenomena such as
      unilateral auditory neglect.

PMID- 10964969
TI  - Role of the lateral preoptic area in sleep-related erectile mechanisms and sleep
      generation in the rat.
AB  - Penile erections are a characteristic phenomenon of paradoxical sleep (PS), or
      rapid eye movement sleep. Although the neural mechanisms of PS-related erections
      are unknown, the forebrain likely plays a critical role (Schmidt et al., 1999).
      The preoptic area is implicated in both sleep generation and copulatory
      mechanisms, suggesting it may be a primary candidate in PS erectile control.
      Continuous recordings of penile erections, body temperature, and sleep-wake
      states were performed before and up to 3 weeks after ibotenic acid lesions of the
      preoptic forebrain in three groups of rats. Neurotoxic lesions involving the
      medial preoptic area (MPOA) and anterior hypothalamus (n = 5) had no significant
      effects on either erectile activity or sleep-wake architecture. In contrast,
      bilateral lesions of the lateral preoptic region, with (n = 4) or without (n = 5)
      MPOA involvement, resulted in a significant decrease in the number of erections
      per hour of PS, number of PS-related erections, and PS phases exhibiting an
      erection. Lesion analysis revealed that the candidate structures for PS erectile
      control include both the lateral preoptic area (LPOA) and ventral division of the
      bed nucleus of the stria terminalis; however, lesions of the LPOA were the most
      effective in disrupting PS erectile activity. LPOA lesioning also resulted in a
      long-lasting insomnia, characterized by the significant increase in wakefulness
      and decrease in slow wave sleep (SWS). PS architecture and waking-state erections
      remained unchanged after lesion in all groups. These data identify an essential
      role of the LPOA in both PS-related erectile mechanisms and SWS generation.
      Moreover, higher erectile mechanisms appear to be context-specific because LPOA
      lesioning selectively disrupted PS-related erections while leaving waking-state
      erections intact.

PMID- 10964970
TI  - Neuronal and glial membrane potentials during sleep and paroxysmal oscillations
      in the neocortex.
AB  - This study investigated the fluctuations in the membrane potential of cortical
      neurons and glial cells during the slow sleep oscillation and spike-wave (SW)
      seizures. We performed dual neuron-glia intracellular recordings together with
      multisite field potential recordings from cortical suprasylvian association areas
      5 and 7 of cats under ketamine-xylazine anesthesia. Electrical stimuli applied to
      the cortex elicited responses consisting of a biphasic depolarization in glial
      cells, which was associated with an EPSP-IPSP sequence in neurons. During the
      slow (<1 Hz) oscillation, extracellular measurements of the potassium
      concentration revealed periodic increases with an amplitude of 1-2 mm, similar in
      shape to glial activities. We suggest that, through their uptake mechanisms, glia
      cells modulate the neuronal excitability and contribute to the pacing of the slow
      oscillation. The slow oscillation often evolved into SW paroxysms, mimicking
      sleep-triggered seizures. This transition was associated with increased coupling
      between the depolarizing events in neurons and glial cells. During seizures, the
      glial membrane potential displayed phasic negative events related to the onset of
      the paroxysmal depolarizing shifts in neurons. These events were not voltage
      dependent and increased their incidence and amplitude with the development of the
      seizure. It is suggested that the intraglial transient negativities represent
      field reflections of synchronized neuronal potentials. We propose that the
      mechanisms underlying the neuron-glia communication include, besides the
      traditional neurotransmitter- and ion-mediated pathways, field effects crossing
      their membranes as a function of the state of the cortical network.

PMID- 10964971
TI  - Dopamine D1 receptors synergize with D2, but not D3 or D4, receptors in the
      striatum without the involvement of action potentials.
AB  - The widespread biological actions of the neurotransmitter dopamine (DA) are
      mediated by two classes of receptor, the D(1) class (D(1) and D(5)) and the D(2)
      class (D(2), D(3), and D(4)), which interact synergistically in many paradigms,
      such as DA agonist-stimulated motor behavior and striatal c-fos expression.
      Understanding the mechanism(s) of this interaction has been impeded by a
      controversy regarding the cellular localization of D(1) and D(2) class receptors.
      To address this issue from a functional point of view, we elicited striatal Fos
      by combined administration of a D(1) class and a D(2) class agonist either in the
      presence or absence of the fast sodium channel blocker tetrodotoxin (TTX).
      Striatal Fos elicited by direct D(1)/D(2) stimulation was not reduced by TTX. By
      contrast, TTX greatly attenuated the Fos response evoked by cocaine or GBR 12909.
      In separate experiments using antagonists that distinguish among members of the
      D(2) class of receptors, amphetamine-stimulated Fos and motor behavior were
      attenuated dose-dependently by the selective D(2) antagonist L-741,626, but not
      by the selective D(3) antagonist U99194A or the D(4)-selective antagonist L
      745,870. Because Fos expression in the paradigms that were used occurs in
      enkephalin-negative striatonigral neurons, which show limited coexpression of
      D(1) and D(2) receptors, the present findings taken together suggest the
      intriguing possibility that D(1)/D(2) synergism may be mediated by D(1) and D(2)
      receptors residing on separate striatal neurons and interacting in a manner that
      is not dependent on action potentials.

PMID- 10964972
TI  - Nonrenewal statistics of electrosensory afferent spike trains: implications for
      the detection of weak sensory signals.
AB  - The ability of an animal to detect weak sensory signals is limited, in part, by
      statistical fluctuations in the spike activity of sensory afferent nerve fibers.
      In weakly electric fish, probability coding (P-type) electrosensory afferents
      encode amplitude modulations of the fish's self-generated electric field and
      provide information necessary for electrolocation. This study characterizes the
      statistical properties of baseline spike activity in P-type afferents of the
      brown ghost knifefish, Apteronotus leptorhynchus. Short-term variability, as
      measured by the interspike interval (ISI) distribution, is moderately high with a
      mean ISI coefficient of variation of 44%. Analysis of spike train variability on
      longer time scales, however, reveals a remarkable degree of regularity. The
      regularizing effect is maximal for time scales on the order of a few hundred
      milliseconds, which matches functionally relevant time scales for natural
      behaviors such as prey detection. Using high-order interval analysis, count
      analysis, and Markov-order analysis we demonstrate that the observed
      regularization is associated with memory effects in the ISI sequence which arise
      from an underlying nonrenewal process. In most cases, a Markov process of at
      least fourth-order was required to adequately describe the dependencies. Using an
      ideal observer paradigm, we illustrate how regularization of the spike train can
      significantly improve detection performance for weak signals. This study
      emphasizes the importance of characterizing spike train variability on multiple
      time scales, particularly when considering limits on the detectability of weak
      sensory signals.

PMID- 10964973
TI  - Centrifugal pathways protect hearing sensitivity at the cochlea in noisy
      environments that exacerbate the damage induced by loud sound.
AB  - Loud sounds damage the cochlea, the auditory receptor organ, reducing hearing
      sensitivity. Previous studies demonstrate that the centrifugal olivocochlear
      pathways can moderately reduce these temporary threshold shifts (TTSs),
      protecting the cochlea. This effect involves only the olivocochlear pathway
      component known as the crossed medial olivocochlear system pathway, originating
      from the contralateral brainstem and terminating on outer hair cells in the
      cochlea. Here I demonstrate that even moderate noise backgrounds can
      significantly exacerbate the cochlear TTSs induced by loud tones, but this is
      prevented because in such conditions there is additional activation of uncrossed
      olivocochlear pathways, enhancing protection of cochlear hearing sensitivity.
      Activation of the uncrossed pathways differs from that of the crossed pathway in
      that it is achieved only in noise backgrounds but can then be obtained under
      monaural conditions of loud tone and background noise. In contrast, activation of
      the crossed pathway is achieved only by binaural loud tones and is not further
      enhanced by background noise. Thus, conjoint activation of both crossed and
      uncrossed efferent pathways can occur in noise backgrounds to powerfully protect
      the cochlea under conditions similar to those encountered naturally by humans.

PMID- 10964974
TI  - Superior water maze performance and increase in fear-related behavior in the
      endothelial nitric oxide synthase-deficient mouse together with monoamine changes
      in cerebellum and ventral striatum.
AB  - Nitric oxide (NO) has been implicated in the control of emotion, learning, and
      memory. We have examined endothelial NO synthase-deficient mice (eNOS-/-) in
      terms of habituation to an open field, elevated plus-maze behavior, Morris water
      maze performance, and changes in cerebral monoamines. In the open field, eNOS-/-
      animals were less active than wild-type controls but showed unimpaired
      habituation. In the plus-maze, an anxiogenic effect was observed. Proceeding from
      previous findings of deficits in hippocampal and neocortical long-term
      potentiation (LTP) in our eNOS-/- mice, we investigated whether these animals
      also express deficits in learning tasks that have been linked to hippocampal
      function and LTP. Unexpectedly, eNOS gene disruption led to accelerated place
      learning in the water maze. Furthermore, during long-term retention and reversal
      learning, eNOS-/- mice showed improved performance. In a cued version of the
      water maze task, eNOS-/- and control mice did not differ, implying that the
      superior performance of eNOS-/- animals on the former tasks cannot be attributed
      solely to differences in sensorimotor capacities. The neurochemical evaluation of
      the eNOS-/- mice revealed increases in the concentrations of the serotonin
      metabolite 5-HIAA in the cerebellum, together with an accelerated serotonin
      turnover in the frontal cortex. Furthermore, eNOS-/- mice had a higher dopamine
      turnover in the ventral striatum. These findings are discussed in terms of
      possible concomitant effects on physiological parameters, such as a decreased
      reactivity of GABAergic neurotransmission or changes in vascular functions, and
      effects on behavioral processes related to reinforcement, learning, and emotion.

PMID- 10964975
TI  - Lesions of the amygdala central nucleus alter performance on a selective
      attention task.
AB  - Previous studies showed a role for the amygdala central nucleus (CN) in
      attentional processing during the acquisition of Pavlovian associations. Both the
      acquisition of conditioned orienting responses and the surprise-induced
      enhancement in the ability of conditioned stimuli to enter into new associations
      depend on the integrity of CN. In this experiment, the role of CN in the
      performance of a well-learned selective attention task was examined. Rats with
      ibotenic acid lesions of CN and control rats first learned a discrete-trial,
      multiple-choice reaction time task. On each trial, after a constant-duration
      ready signal, the rats were required to poke their noses into one of three ports,
      guided by the brief illumination of one of those ports. Rats with CN lesions were
      slower to acquire the task than control rats but showed equivalent asymptotic
      sustained performance. Subsequent attentional challenges, which included reducing
      the duration of the port illumination and varying the duration of the ready
      signal, had greater impact on the performance of lesioned than control rats.
      These data resemble those reported from similar tasks after damage to the basal
      forebrain (BF) system. Together with earlier findings, these data support a role
      for CN in modulating visuospatial attention in action as well as in the
      acquisition of associations, perhaps by way of its projections to BF cholinergic
      systems.

PMID- 10964977
TI  - Suppressed injury-induced rise in spinal prostaglandin E2 production and reduced
      early thermal hyperalgesia in iNOS-deficient mice.
AB  - It is widely accepted that peripheral injury increases spinal inducible
      cyclooxygenase (COX-2) expression and prostaglandin E(2) (PGE(2)) formation as
      key mediators of nociceptive sensitization. Here, we used inducible nitric oxide
      synthase (iNOS) gene-deficient (iNOS-/-) mice to determine the contribution of
      iNOS-derived nitric oxide (NO) to this process. iNOS-/- mice exhibited reduced
      thermal hyperalgesia after zymosan injection. Spinal NO and PGE(2) formation both
      remained at baseline levels, in contrast to wild-type (wt) mice. In wt mice
      reduced hyperalgesia similar to that seen in iNOS-/- mice was induced by local
      spinal, but not by systemic treatment with the iNOS inhibitor l-NIL, suggesting
      that the reduced heat sensitization in iNOS-/- mice was attributable to the lack
      of spinal rather than peripheral iNOS. Two additional observations indicate that
      the antinociceptive effects of iNOS inhibition are dependent on a loss of
      stimulation of PG synthesis. First, intrathecal injection of the COX inhibitor
      indomethacin, which exerted pronounced antinociceptive effects in wt mice, was
      completely ineffective in iNOS-/- mice. Second, treatment with the NO donor RE
      2047 not only completely restored spinal PG production and thermal sensitization
      in iNOS-/- mice but also its sensitivity to indomethacin. In both types of mice
      induction of thermal hyperalgesia was accompanied by similar increases in COX-1
      and COX-2 mRNA expression. The stimulation of PG production by NO therefore
      involves an increase in enzymatic activity, rather than an alteration of COX gene
      expression. These results indicate that NO derived from spinal iNOS acts as a
      fast inductor of spinal thermal hyperalgesia.

PMID- 10964976
TI  - Disruption of arcuate/paraventricular nucleus connections changes body energy
      balance and response to acute stress.
AB  - The mediobasal hypothalamus regulates functions necessary for survival, including
      body energy balance and adaptation to stress. The purpose of this experiment was
      to determine the contribution of the arcuate nucleus (ARC) in controlling these
      two functions by the paraventricular nucleus (PVN). Circular, horizontal cuts
      (1.0 mm radius) were placed immediately above the anterior ARC to sever afferents
      to the PVN. In shams the knife was lowered to the same coordinates but was not
      rotated. Food intake and body weight were monitored twice daily, at the beginning
      and end of the light cycle, for 1 week. On the final day the animals were
      restrained for 30 min. Lesioned animals had increased food intake in light and
      dark periods, higher weight gain per day, and more body fat as compared with
      shams. There was no difference in caloric efficiency. Unlike shams, lesioned rats
      had no predictable relationship between plasma insulin and leptin. Plasma ACTH
      was increased at 0 min in lesioned rats but was decreased 15 and 30 min after
      restraint as compared with shams. There was no difference in plasma
      corticosterone. Immunostaining revealed that alpha-melanocortin (alphaMSH) and
      neuropeptide Y (NPY) accumulated below the cuts, and both were decreased in PVN.
      Food intake and body weight were correlated negatively to alphaMSH, but not NPY
      in PVN. There was no difference in proopiomelanocortin (POMC) mRNA, but NPY mRNA
      was reduced in the ARC of lesioned animals. We conclude that ARC controls body
      energy balance in unstressed rats, possibly by alphaMSH input to PVN, and that
      ARC also is necessary for PVN regulation of ACTH.

PMID- 10964978
TI  - Nitric oxide and the oxytocin system in pregnancy.
AB  - We examined the functional role of the nitric oxide (NO)-producing system in
      magnocellular neurons and how this changes at the end of pregnancy, using a
      combination of blood sampling and oxytocin radioimmunoassay, electrophysiology,
      immunocytochemistry for Fos expression, and in situ hybridization histochemistry.
      In urethane-anesthetized virgin rats, systemic administration of NO synthase
      (NOS) inhibitors led to a facilitation of oxytocin release evoked by hyperosmotic
      stimulation. Direct application of the NO donor sodium nitroprusside to the
      supraoptic nucleus by in vivo microdialysis inhibited the electrical activity of
      both oxytocin neurons and vasopressin neurons, whereas direct application of an
      NOS inhibitor increased electrical activity, indicating that endogenous NO acts
      within the supraoptic nucleus to inhibit neuronal activity. However, during late
      pregnancy, the influence of endogenous NO is dramatically downregulated,
      reflected by a reduced expression of neuronal NOS mRNA in these neurons and a
      loss of efficacy of NOS inhibitors on stimulus-evoked oxytocin release. This
      downregulation may cause the oxytocin system to become more excitable at term,
      resulting in the capacity for greater release of oxytocin during parturition.

PMID- 10964979
TI  - Postural and anticonvulsant effects of inhibition of the rat subthalamic nucleus.
AB  - The subthalamic nucleus (STN) plays a crucial role as a regulator of basal
      ganglia outflow by providing excitatory glutamatergic input into the two output
      nuclei of the basal ganglia, substantia nigra pars reticulata (SNpr), and
      entopeduncular nucleus. This study examined the effects of suppressing activity
      in the STN of the awake, behaving rat. Specifically, we evaluated the effects of
      unilateral and bilateral focal inhibition of STN on posture, locomotion, and
      susceptibility to limbic motor seizures. Unilateral microinjection of a GABA(A)
      receptor agonist (muscimol, 200 pmol) into STN produced a site-dependent
      contralaterally directed postural asymmetry without locomotor activation. This
      effect differed from responses produced by the same dose of muscimol placed into
      SNpr, which included locomotor activation in addition to contralaterally directed
      postural asymmetry. Locomotor activation and postural asymmetry were obtained
      also after blockade of glutamate transmission in SNpr by the unilateral
      application of kynurenate (100 nmol). Our observation that STN inhibition did not
      induce the locomotor activation characteristic of SNpr inhibition suggests that
      there are glutamatergic inputs to SNpr, other than those from STN, that are
      responsible for controlling locomotion. Bilateral, but not unilateral, injection
      of muscimol (200 pmol) into STN protected against limbic motor seizures evoked
      either by intravenous bicuculline or by focal application of bicuculline into
      anterior piriform cortex (area tempestas). These results demonstrate that focal
      inhibition of STN reproduces the postural asymmetry and anticonvulsant actions
      that are obtained with the inhibition of SNpr. This provides behavioral support
      for the concept that STN contributes a crucial tonic excitatory (glutamatergic)
      drive to the rat SNpr.

PMID- 10964981
TI  - The initial step of the thermal unfolding of 3-isopropylmalate dehydrogenase
      detected by the temperature-jump Laue method.
AB  - A temperature-jump (T-jump) time-resolved X-ray crystallographic technique using
      the Laue method was developed to detect small, localized structural changes of
      proteins in crystals exposed to a temperature increase induced by laser
      irradiation. In a chimeric protein between thermophilic and mesophilic 3
      isopropylmalate dehydrogenases (2T2M6T), the initial structural change upon T
      jump to a denaturing temperature (approximately 90 degrees C) was found to be
      localized at a region which includes a beta-turn and a loop located between the
      two domains of the enzyme. A mutant, 2T2M6T-E110P/S111G/S113E, having amino acid
      replacements in this beta-turn region with the corresponding residues of the
      thermophilic enzyme, showed greater stability than the original chimera (increase
      of T:(m) by approximately 10 degrees C) and no T-jump-induced structural change
      in this region was detected by our method. These results indicate that thermal
      unfolding of the original chimeric enzyme, 2T2M6T, is triggered in this beta-turn
      region.

PMID- 10964980
TI  - Adjustable amplification of synaptic input in the dendrites of spinal motoneurons
      in vivo.
AB  - The impact of neuromodulators on active dendritic conductances was investigated
      by the use of intracellular recording techniques in spinal motoneurons in the
      adult cat. The well known lack of voltage control of dendritic regions during
      voltage clamp applied at the soma was used to estimate dendritic amplification of
      a steady monosynaptic input generated by muscle spindle Ia afferents. In
      preparations deeply anesthetized with pentobarbital, Ia current either decreased
      with depolarization or underwent a modest increase at membrane potentials above 
      40 mV. In unanesthetized decerebrate preparations (which have tonic activity in
      axons originating in the brainstem and releasing serotonin or norepinephrine),
      active dendritic currents caused strong amplification of Ia input. In the range
      of -50 to -40 mV, peak Ia current was over four times as large as that in the
      pentobarbital-anesthetized preparations. Exogenous administration of a
      noradrenergic agonist in addition to the tonic activity further enhanced
      amplification (sixfold increase). Amplification was not seen in preparations with
      spinal transections. Overall, the dendritic amplification with moderate or strong
      neuromodulatory drive was estimated to be large enough to allow the motoneurons
      innervating slow muscle fibers to be driven to their maximum force levels by
      remarkably small synaptic inputs. In these cells, the main role of synaptic input
      may be to control the activation of a highly excitable dendritic tree. The
      neuromodulatory control of synaptic amplification provides motor commands with
      the potential to adjust the level of amplification to suit the demands of
      different motor tasks.

PMID- 10964982
TI  - Protein structure alignment using environmental profiles.
AB  - A new protein structure alignment procedure is described. An initial alignment is
      made by comparing a one-dimensional list of primary, secondary and tertiary
      structural features (profiles) of two proteins, without explicitly considering
      the three-dimensional geometry of the structures. The alignment is then
      iteratively refined in the second step, in which new alignments are found by
      three-dimensional superposition of the structures based on the current alignment.
      This new procedure is fast enough to do all-against-all structural comparisons
      routinely. The procedure sometimes finds an alignment that suggests an
      evolutionary relationship and which is not normally obtained if only geometry is
      considered. All pair-wise comparisons were made among 3539 protein structural
      domains that represent all known protein structures. The resulting 3539 z-scores
      were used to cluster the proteins. The number of main clusters increased
      continuously as the z-cutoff was raised, but the number of multiple-member
      clusters showed a maximum at z-cutoff values of 5.0 and 5.5. When a z-cutoff
      value of 5.0 was used, the total number of main clusters was 2043, of which only
      336 clusters had more than one member.

PMID- 10964983
TI  - Structure-derived substitution matrices for alignment of distantly related
      sequences.
AB  - Sequence alignment is a standard method to infer evolutionary, structural, and
      functional relationships among sequences. The quality of alignments depends on
      the substitution matrix used. Here we derive matrices based on superimpositions
      from protein pairs of similar structure, but of low or no sequence similarity. In
      a performance test the matrices are compared with 12 other previously published
      matrices. It is found that the structure-derived matrices are applicable for
      comparisons of distantly related sequences. We investigate the influence of
      evolutionary relationships of protein pairs on the alignment accuracy.

PMID- 10964984
TI  - Structural and interactional homology of clinically potential trypsin inhibitors:
      molecular modelling of cucurbitaceae family peptides using the X-ray structure of
      MCTI-II.
AB  - Several trypsin inhibitor peptides (with 28-32 amino acid residues) belonging to
      the Cucurbitaceae (LA-1, LA-2, MCTI-I, CMTI-I, CMTI-III, CMTI-IV), characterized
      by a distinctive tertiary fold with three conserved disulphide bonds and with
      mostly arginine at their active centre, were modelled using the high-resolution X
      ray structure of a homologous inhibitor, MCTI-II, isolated from bitter gourd. All
      the inhibitors were modelled in both their native and complexed state with the
      trypsin molecule, keeping the active site the same as was observed in the trypsin
      MCTI-II complex, by homology modelling using the InsightII program. The minimized
      energy profile supported the binding constants (binding behaviour) of the
      inhibitor-trypsin complexes in the solution state. A difference accessible
      surface area (DASA) study of the trypsin with and without inhibitors revealed the
      subsites of trypsin where the inhibitors bind. It revealed that the role of
      mutation of these peptides through evolution is to modulate their inhibitory
      function depending on the biological need rather than changing the overall
      structural folding characteristics which are highly conserved. The minor changes
      of amino acids in the non-conserved regions do not influence significantly the
      basic conformational and interactional sequences at the trypsin binding subsites
      during complex formation.

PMID- 10964985
TI  - Replacement set mutagenesis of the four phosphate-binding arginine residues of
      thymidylate synthase.
AB  - Arginines R23, R178, R179 and R218 in thymidylate synthase (TS, EC 2. 1.1.45) are
      hydrogen bond donors to the phosphate moiety of the substrate, dUMP. In order to
      investigate how these arginines contribute to enzyme function, we prepared
      complete replacement sets of mutants at each of the four sites in Lactobacillus
      casei TS. Mutations of R23 increase K:(m) for dUMP 2-20-fold, increase K:(m) for
      cofactor 8-40-fold and decrease k(cat) 9-20-fold, reflecting the direct role of
      the R23 side chain in binding and orienting the cofactor in ternary complexes of
      the enzyme. Mutations of R178 increase K:(m) for dUMP 40-2000-fold, increase
      K:(m) for cofactor 3-20-fold and do not significantly affect k(cat). These
      results are consistent with the fact that this residue is an integral part of the
      dUMP-binding wall and contributes to the orientation and ordering of several
      other dUMP binding residues. Kinetic parameters for all R179 mutations except
      R179P were not significantly different from wild-type values, reflecting the fact
      that this external arginine does not directly contact the cofactor or other
      ligand-binding residues. R218 is essential for the structure of the catalytic
      site and all mutations of this arginine except R218K were inactive.

PMID- 10964986
TI  - ScFv multimers of the anti-neuraminidase antibody NC10: shortening of the linker
      in single-chain Fv fragment assembled in V(L) to V(H) orientation drives the
      formation of dimers, trimers, tetramers and higher molecular mass multimers.
AB  - Synthetic genes encoding single-chain variable fragments (scFvs) of NC10 anti
      neuraminidase antibody were constructed by joining the V(L) and V(H) domains with
      linkers of fifteen, five, four, three, two, one and zero residues. These V(L)
      V(H) constructs were expressed in Escherichia coli and the resulting proteins
      were characterized and compared with the previously characterized NC10 scFv
      proteins assembled in V(H)-V(L) orientation. Size-exclusion chromatography and
      electron microscope images of complexes formed between various NC10 scFvs and
      anti-idiotype Fab' were used to analyse the oligomeric status of these scFvs. The
      result showed that as the linker length between V(L) and V(H) was reduced,
      different patterns of oligomerization were observed compared with those with V(H)
      V(L) isomers. As was the case for V(H)-V(L) orientation, the scFv-15 V(L)-V(H)
      protein existed mainly as a monomer whereas dimer (diabody) was a predominant
      conformation for the scFv-5, scFv-4 and scFv-3 V(L)-V(H) proteins. In contrast to
      the V(H)-V(L) isomer, direct ligation of V(L) to V(H) led to the formation of
      predominantly a tetramer (tetrabody) rather than to an expected trimer
      (triabody). Furthermore, the transition between dimers and higher order oligomers
      was not as distinct as for V(H)-V(L). Thus reducing the linker length in V(L)
      V(H) from three to two residues did not precisely dictate a transition between
      dimers and tetramers. Instead, two-residue as well as one-residue linked scFvs
      formed a mixture of dimers, trimers and tetramers.

PMID- 10964987
TI  - Characterization of diphtheria fusion proteins targeted to the human interleukin
      3 receptor.
AB  - Diphtheria fusion proteins are chimeric proteins consisting of the catalytic and
      translocation domains of diphtheria toxin (DT(388)) linked through an amide bond
      to one of a variety of peptide ligands. The ligand targets the molecule to cells
      and the toxin enters the cell, inactivates protein synthesis and induces cell
      death. Diphtheria fusion proteins directed to human myeloid leukemic blasts are a
      novel class of therapeutics for patients with chemotherapy refractory myeloid
      leukemia. Because of the presence of interleukin-3 (IL3) receptors on myeloid
      leukemic progenitors and its absence from mature myeloid cells, we synthesized
      four bacterial expression vectors encoding DT(388) fused to human IL3. Different
      molecules were engineered to assess the effects of modifications on yield, purity
      and potency of product. The constructs differed in the size of the linker peptide
      between the DT(388) and IL3 domains and in the presence or absence of an
      oligohistidine tag on the N- or C-terminus. Escherichia coli were transformed and
      recombinant protein induced and purified from inclusion bodies. Similar final
      yields of 3-6 mg of purified protein per liter of bacterial culture were obtained
      with each of the four molecules. Purity ranged from 70 to 90% after partial
      purification by anion-exchange, size-exclusion chromatography and/or nickel
      affinity chromatography. Proteins were soluble and stable at 4 degrees C and -80
      degrees C in phosphate-buffered saline at 0.03-0.5 mg/ml. The fusion proteins
      showed predicted molecular weights by SDS-PAGE, HPLC and tandem mass spectrometry
      and had full ADP-ribosylating activities. Each was immunoreactive with antibodies
      to DT(388) and IL3. Each of the fusion proteins with the exception of the one
      with an N-terminal oligohistidine tag showed full IL3 receptor binding affinity
      (K:(d) = 3 nM) and potent and selective cytotoxicity to IL3 receptor positive
      human myeloid leukemia cell lines (IC(50) = 5-10 pM). In contrast, the N-terminal
      histidine-tagged fusion protein bound IL3 receptor with a 10-fold lower affinity
      and was 10-fold less cytotoxic to IL3 receptor positive blasts. Thus, we report a
      series of novel, biologically active DT(388)IL3 fusion proteins for potential
      therapy of patients with receptor positive myeloid leukemias.

PMID- 10964988
TI  - Construction of a diabody (small recombinant bispecific antibody) using a
      refolding system.
AB  - Diabodies are the recombinant bispecific antibodies (BsAbs), constructed from
      heterogeneous single-chain antibodies. Usually, diabodies have been prepared from
      bacterial periplasmic fraction using a co-expression vector (i.e. genes encoding
      two chains were tandemly located under the same promoter). Some diabodies,
      however, cannot be expressed as a soluble material owing to inclusion body
      formation, which limits the utilization of diabodies in various fields. Here we
      report an improved method for the construction of diabodies using a refolding
      system. As a model, a bispecific diabody binding to adenocarcinoma-associated
      antigen MUC1 and to CD3 on T cells was studied. One chain consisted of a VH
      specific for MUC1 linked to a VL specific for CD3 with a short polypeptide linker
      (GGGGS). The second was composed of a VL specific for MUC1 linked to a VH
      specific for CD3. The two hetero scFvs were independently obtained from
      intracellular insoluble fractions of Escherichia coli, purified, mixed
      stoichiometrically (at an equivalent molar ratio of 1:1) and refolded. The
      refolded two hetero scFv has a hetero-dimeric structure, with complete
      specificity for both target cells [i.e. MUC1 positive cells and CD3 positive
      lymphokine-activated killer cells with a T cell phenotype (T-LAK)]. Evaluation of
      the in vitro efficacy of T-LAK with the diabody by growth inhibition assay of
      cancer cells demonstrated maximum growth inhibition of cancer cells to reach
      approximately 98% at an effector:target ratio (E:T ratio) of 10, almost identical
      with that with anti-MUC1xanti-CD3 chemically synthesized BsAbs (c-BsAbs). This is
      the first report of the construction of a diabody using a refolding system.

PMID- 10964989
TI  - Phages from landscape libraries as substitute antibodies.
AB  - In 'landscape' phage, as in traditional phage-display constructs, foreign
      peptides or proteins are fused to coat proteins on the surface of a filamentous
      phage particle. Unlike conventional constructs, however, each virion displays
      thousands of copies of the peptide in a repeating pattern, subtending a major
      fraction of the viral surface. The phage body serves as an interacting scaffold
      to constrain the peptide into a particular conformation, creating a defined
      organic surface structure ('landscape') that varies from one phage clone to the
      next. By testing landscape libraries with three representative antigens
      (streptavidin from the bacterium Streptomyces avidinii, avidin from chicken egg
      white and beta-galactosidase from Escherichia coli) we have shown that landscape
      phages may be used as a new type of substitute antibodies-filaments that can bind
      protein and glycoprotein antigens with nanomolar affinities and high specificity.
      In many ways these substitute antibodies are more convenient than their natural
      immunoglobulin counterparts.

PMID- 10964990
TI  - Characterization of function and activity of domains A, B and C of xylanase C
      from Fibrobacter succinogenes S85.
AB  - Xylanase C from the ruminant bacterium Fibrobacter succinogenes is comprised of
      two catalytic domains, A and B, and a third domain, C, of unknown function. The
      DNA coding for domains A and B of xylanase C were separately cloned and expressed
      in Escherichia coli as fusion proteins with glutathione-S:-transferase. The
      fusion proteins were isolated by affinity chromatography on glutathione-Sepharose
      4B, cleaved with thrombin and the released xylanase C catalytic domains A and B
      were purified to apparent homogeneity by anion-exchange chromatography on Mono Q.
      Electrospray mass spectrometry provided a molecular mass of 27 818 Da (expected,
      27 820 Da) for domain B. The pH and temperature optima for activity of domain B
      on oat spelt xylan were 5.0 and 52 degrees C, respectively. A kinetic analysis of
      the activity of the catalytic domain A on oat spelt xylan, birch wood xylan and
      xylooligomers at pH 6.5 and 37 degrees C provided data significantly different to
      those obtained previously with a protease-derived form of the enzyme [Zhu et al.
      (1994) J. Bacteriol. 176, 3885-3894]. The isolated domain A was more active on
      barley-glucan than the protease-derived form and its affinity for birch wood
      xylan was enhanced resulting in greater overall catalytic efficiency as reflected
      by k(cat)/K:(M) values. Likewise, significant differences in the Michaelis-Menten
      parameters K:(M), k(cat) and k(cat)/K:(M) were obtained with domain B compared
      with values previously reported with this domain attached to domain C. In
      general, the presence of domain C appeared to decrease the overall efficiency of
      domain B 7- and 36-fold with birch wood xylan and xylopentaose as substrates,
      respectively, as reflected by values of k(cat)/K:(M). The removal of domain C
      also affected the mode of action of domain B such that it more closely resembled
      that of catalytic domain A. However, no change in either pH and temperature
      optima or stability were found with domain B compared with the combined domains B
      and C. The function of domain C remains unknown, but hydrophobic cluster analysis
      indicated that it may belong to a class of dockerin domains involved in the
      protein-protein interactions of cellulolytic and xylanolytic complexes.

PMID- 10964991
TI  - Remarkable thermal stability of doubly intramolecularly cross-linked hen
      lysosymeProtein engineering (2000), 3, 193-196

PMID- 10964992
TI  - Highlights in ovarian cancer.
AB  - The ovarian cancer presentations at the 2000 ASCO meeting did not yield any major
      paradigm shifts in the treatment of women with epithelial ovarian cancer.
      Emphasis at this year's meeting focused on the potential incorporation of drugs
      such as topotecan, oxaliplatin, doxil, and gemcitabine into the initial treatment
      strategies of women with advanced ovarian cancer. These studies included the
      introduction of several active and tolerable regimens that are potentially worthy
      of direct comparison to the carboplatin and paclitaxel combination. In the woman
      with recurrent or persistent ovarian cancer there was a greater focus on phase
      III studies directly comparing various chemotherapy strategies in the treatment
      of women with recurrent disease. This included the comparisons of single-versus
      two-drug salvage regimens, alternate salvage schedules, and direct comparison of
      agents active in taxane- and platinum-resistant disease. Finally, several early
      studies of novel non-chemotherapeutic strategies were presented.

PMID- 10964993
TI  - Lung cancer highlights.
AB  - Have we made any progress in the treatment of advanced non-small cell lung cancer
      (NSCLC) over the past 15 years? After hearing the Eastern Cooperative Oncology
      Group (ECOG) 1594 presented by Dr. Joan Schiller at the plenary session of the
      36th Annual Meeting of ASCO, it is hard to be certain. SCHILLER: reported the
      results of one of the world's largest randomized trials in metastatic lung cancer
      comparing four platinum-based doublets. There were no differences in survival
      (primary endpoint) or response between these four regimens, although the
      cisplatin/gemcitabine arm had a superior time to progression. In her commentary
      on this study, Dr. Francis Shepherd concluded that progress in the treatment of
      metastatic lung cancer has occurred at "a snail's pace." Despite the
      disappointing results of ECOG 1594, there were notable trials describing new
      agents with novel mechanisms of action reported at this year's ASCO meeting. In
      small-cell lung cancer, the combination of cisplatin/ irinotecan was found to be
      superior to cisplatin/etoposide. For NSCLC, novel agents Iressa anti-epidermal
      growth factor receptor tyrosine kinase and anti-vascular endothelial growth
      factor monoclonal antibody appear promising.

PMID- 10964994
TI  - Hematologic malignancies: selected abstracts and commentary.
AB  - ASCO 2000 did not offer revolutionary new advances in the treatment of
      hematologic malignancies. However, reports at the meeting built incrementally on
      gains established over the past several years. The meeting continued to highlight
      advances in the targeted therapy of hematologic malignancies. Excitement abounds
      regarding the clinical development of STI 571, a rationally designed tyrosine
      kinase inhibitor, for the treatment of chronic myelogenous leukemia. Studies
      further defined the role monoclonal antibody treatment for non-Hodgkin's lymphoma
      and more mature data were presented on both unconjugated antibody therapy and
      radioimmunoconjugates. In disease detection, important data were presented to
      clarify the role of positron emission tomography scans in the staging and follow
      up of lymphoid malignancies. The following review summarizes key abstracts
      presented at the 2000 ASCO meeting and will elaborate on the implications of
      these findings for disease management.

PMID- 10964995
TI  - Breast cancer update.
AB  - The large number of excellent presentations on breast cancer at this year's ASCO
      meeting reflects the enormous interest in clinical trials of this common disease.
      In the reports of adjuvant hormonal therapy, the most interesting included
      Abstract 273 by Boccardo et al., who reported that postmenopausal women with
      estrogen receptor positive (ER(+)) cancers who had already completed three years
      of tamoxifen experienced better overall survival if treated with two years of
      subsequent aminoglutethimide (a first-generation aromatase inhibitor) rather than
      another two years of tamoxifen. This whets our appetite for studies currently
      under way to define the role of third-generation aromatase inhibitors in the
      adjuvant setting. A report by FISHER: from the National Surgical Adjuvant Breast
      and Bowel Project B-23 study (Abstract 277) provided confirmation of what is
      rapidly becoming accepted, that the addition of tamoxifen to chemotherapy does
      not benefit breast cancer patients with negative lymph nodes who have ER(-)
      cancers. In premenopausal women, another report of the benefit of hormonal
      therapy, this time by the French Adjuvant Study Group using complete hormonal
      blockade with a luteinizing hormone-releasing hormone agonist and tamoxifen
      (Abstract 279) showed that hormonal therapy can be at least as good as, if not
      better, than six cycles of 5-fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2),
      cyclophosphamide 500 mg/m(2) in terms of disease-free survival and overall
      survival. Among the papers on adjuvant chemotherapy, a controversial paper from
      the German Adjuvant Breast Cancer Group reported that three cycles of CMF (a dose
      intense regimen with all three drugs being given on days 1 and 8) were as good as
      six cycles (Abstract 283). Another report, from the International Breast Cancer
      Study Group, raised the controversial question of whether there really is much
      added benefit from the addition of chemotherapy to tamoxifen in postmenopausal
      women with negative lymph nodes if their tumors have ERs (Abstract 281). A second
      study (the first was the CALGB study reported at ASCO in 1998) showing a benefit
      to the addition of Taxol to an anthracycline-based adjuvant regimen, was reported
      from the M.D. Anderson Cancer Center (Abstract 285), giving further impetus to
      the inclusion of Taxol in standard adjuvant treatment. Finally, there were a
      number of interesting presentations on HER-2. Reported here are three of these,
      all addressing the effect of HER-2 overexpression on the response to hormonal
      therapy. Taken together, they uphold the emerging concern that women with ER(+)
      cancers may not benefit significantly from endocrine treatment if the tumors also
      overexpress HER-2. Observations such as these will afford us the ability to
      predict more accurately which women will benefit from specific treatments.

PMID- 10964996
TI  - Prophylactic cranial irradiation in small-cell lung cancer.
AB  - Prophylactic cranial irradiation is now known to improve survival to a
      significant degree in small-cell lung cancer (SCLC) patients; this is in addition
      to its established role in preventing the disabling symptoms of brain metastases.
      New information indicates that it confers a survival benefit for limited or
      extensive stage SCLC patients gaining a complete response in the chest. A review
      of causes of cerebral dysfunction as a complication indicates that such problems
      can be due to suboptimal radiation fractionation, chemotherapy, or an
      inappropriate combination of prophylactic brain irradiation with chemotherapy.
      Optimum treatment with prophylactic brain irradiation has been shown not to cause
      adverse effects with detailed psychometric testing. Several additional sources of
      information can be drawn together to suggest a dose-response pattern for
      prophylactic brain irradiation, leading to the recommendation that a dose of 25
      36 Gy is optimal, delivered in 2-3 Gy daily fractions after the completion of
      chest irradiation and chemotherapy. This will be better defined in future
      clinical trials.

PMID- 10964997
TI  - Prophylactic cranial irradiation in small-cell lung cancer: is it still
      controversial or is it a no-brainer?

PMID- 10964998
TI  - SPIKES-A six-step protocol for delivering bad news: application to the patient
      with cancer.
AB  - We describe a protocol for disclosing unfavorable information-"breaking bad news"
      to cancer patients about their illness. Straightforward and practical, the
      protocol meets the requirements defined by published research on this topic. The
      protocol (SPIKES) consists of six steps. The goal is to enable the clinician to
      fulfill the four most important objectives of the interview disclosing bad news:
      gathering information from the patient, transmitting the medical information,
      providing support to the patient, and eliciting the patient's collaboration in
      developing a strategy or treatment plan for the future. Oncologists, oncology
      trainees, and medical students who have been taught the protocol have reported
      increased confidence in their ability to disclose unfavorable medical information
      to patients. Directions for continuing assessment of the protocol are suggested.

PMID- 10964999
TI  - Intracranial germ cell tumors.
AB  - Intracranial germ cell tumors are a heterogeneous group of lesions which occur in
      children and adults. Within the classification of intracranial germ cell tumors,
      there are a variety of different tumor types which carry different prognoses. The
      diagnosis of an intracranial germ cell tumor usually requires histological
      information, but a subgroup of tumors will secrete specific tumor markers,
      including alpha-fetoprotein and beta-human chorionic gonadotropin, which may
      obviate the need for surgical intervention. The management of intracranial germ
      cell tumors in both children and adults remains unsettled. Germinomas have a good
      prognosis, as over 90% of patients can be effectively treated with radiation
      therapy. The dose and volume of radiation therapy needed for disease control is
      not well established, and controversy exists concerning the need for whole brain
      or craniospinal radiation therapy for localized tumors. Germinomas are also
      chemosensitive and recent reports suggest that the dose and volume of radiation
      therapy required for disease control can be lessened with the addition of
      adjuvant chemotherapy. The outcome for patients with nongerminomatous germ cell
      tumors is less favorable. Radiation therapy alone will result in disease control
      in 40%-60% of patients. The addition of chemotherapy to radiation therapy may
      improve the rate of survival.

PMID- 10965000
TI  - The role of prognostic features in the treatment of childhood acute lymphoblastic
      leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is
      among the most curable of the pediatric malignancies. Many clinical, biological,
      genetic, and molecular features have been identified as having prognostic
      significance in the outcome of patients with ALL. The standard features are age
      and WBC at diagnosis, with infants (less than one year), adolescents (greater
      than nine years), and children with WBC above 50,000/microl being at higher risk.
      Certain chromosomal abnormalities are also strong predictors; in particular, the
      Philadelphia chromosome and MLL gene rearrangements (especially in infants) are
      adverse features, while TEL-AML1 is favorable. It is important to note, however,
      that even the most important known predictors explain only a small proportion of
      the variability in outcome. These features are currently used to tailor the
      intensity of treatment so that the toxicity of treatment can be minimized and
      cure rates can continue to improve. This article reviews time-honored prognostic
      features, recent advances, and future directions in this field.

PMID- 10965001
TI  - Fox Chase Network: Fox Chase Cancer Center's community hospital affiliation
      program.
AB  - Fox Chase Cancer Center developed a format for affiliation with community
      providers in 1986. Fox Chase Network was formed to establish hospital-based
      community cancer centers to increase access to patients involved in clinical
      research. Under this program, the Fox Chase Network now contributes 500 patients
      per year to prevention and clinical research studies. As relationships with
      community providers form, patient referrals have increased at Fox Chase Cancer
      Center and for each Fox Chase Network member. A dedicated staff is required to
      operate the central office on a day-to-day basis as well as at each affiliate. We
      have found this to be a critical element in each program's success. New
      challenges in the cancer business-increasing volumes with declining revenue-have
      caused us to reconfigure the services offered to affiliates, while maintaining
      true to our mission: to reduce the burden of human cancer.

PMID- 10965002
TI  - Sexuality and cancer: conversation comfort zone.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at
      MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and
      advancing compassionate health care delivery, which provides hope to the patient,
      support to caregivers, and encourages the healing process. The center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers, and gain insight and support from fellow staff members.
      Psychosocial issues profoundly affect patients with cancer. Of the many
      complexities that make up the psychosocial dynamic, perhaps the medical
      profession is most uncomfortable with sexuality. Many elements of sexual behavior
      remain high-profile taboos. A number of diseases and treatments significantly
      affect sexual function. Male and female sexuality were discussed in two separate
      rounds with an emphasis on how to begin a dialogue about sexuality without
      jeopardizing other aspects of the relationship with patients. Three cases were
      presented. A patient with prostate cancer considering treatment options for early
      stage disease and two patients with gynecologic malignancies; one with a
      colostomy following cytoreductive surgery for ovarian cancer and the other with a
      failed vaginal reconstruction for recurrent squamous cell carcinoma of the
      vagina. Staff discussed the wide diversity of response to sexual dysfunction and
      the difficulties that patients face. A sensitive and informed approach to
      discussing sexuality can provide effective support. The elements of successful
      dialogue are presented in the PLISSIT model.

PMID- 10965003
TI  - The molecular perspective: microtubules and the taxanes.

PMID- 10965005
TI  - The basic immunology of ASCO

PMID- 10965004
TI  - Capitol report.

PMID- 10965006
TI  - Increased susceptibility to malaria during the early postpartum period.
AB  - BACKGROUND: Pregnancy is associated with increased susceptibility to malaria. It
      is generally agreed that this increased risk ends with delivery, but the possible
      persistence of increased susceptibility during the puerperium had not been
      investigated. METHODS: From June 1, 1990, to December 31, 1998, we monitored
      exposure to malaria, parasitemia, and morbidity among the residents of a village
      in Senegal in which the rate of transmission of malaria was high. In this
      population we analyzed 71 pregnancies in 38 women from the year before conception
      and through one year after delivery. RESULTS: Among the 38 women, there were 58
      episodes of clinical Plasmodium falciparum malaria during 61,081 person-days of
      observation. The incidence of malaria was 20.2 episodes per 1000 person-months
      during the year preceding conception and 12.0 episodes per 1000 person-months
      during the period from 91 to 365 days after delivery. The incidence of episodes
      of malaria increased significantly during the second and third trimesters of
      pregnancy and reached a maximum of 75.1 episodes per 1000 person-months during
      the first 60 days after delivery. The adjusted relative risk of an episode of
      malaria was 4.1 (95 percent confidence interval, 1.8 to 9.5) during the first 60
      days post partum, as compared with the year preceding pregnancy. The duration of
      fever during the episodes of malaria was longer and the prevalence and density of
      asymptomatic malarial parasitemia were significantly higher during pregnancy and
      the early postpartum period than during the other periods. CONCLUSIONS: Among
      women who live in areas with high rates of transmission of malaria, the
      susceptibility to malaria is highest during the second and third trimesters of
      pregnancy and the early postpartum period.

PMID- 10965007
TI  - Predictors of outcome in severe, asymptomatic aortic stenosis.
AB  - BACKGROUND: Whether to perform valve replacement in patients with asymptomatic
      but severe aortic stenosis is controversial. Therefore, we studied the natural
      history of this condition to identify predictors of outcome. METHODS: During
      1994, we identified 128 consecutive patients with asymptomatic, severe aortic
      stenosis (59 women and 69 men; mean [+/-SD] age, 60+/-18 years; aortic-jet
      velocity, 5.0+/-0.6 m per second). The patients were prospectively followed until
      1998. RESULTS: Follow-up information was available for 126 patients (98 percent)
      for a mean of 22+/-18 months. Event-free survival, with the end point defined as
      death (8 patients) or valve replacement necessitated by the development of
      symptoms (59 patients), was 67+/-5 percent at one year, 56+/-5 percent at two
      years, and 33+/-5 percent at four years. Five of the six deaths from cardiac
      disease were preceded by symptoms. According to multivariate analysis, only the
      extent of aortic-valve calcification was an independent predictor of outcome,
      whereas age, sex, and the presence or absence of coronary artery disease,
      hypertension, diabetes, and hypercholesterolemia were not. Event-free survival
      for patients with no or mild valvular calcification was 92+/-5 percent at one
      year, 84+/-8 percent at two years, and 75+/-9 percent at four years, as compared
      with 60+/-6 percent, 47+/-6 percent, and 20+/-5 percent, respectively, for those
      with moderate or severe calcification. The rate of progression of stenosis, as
      reflected by the aortic-jet velocity, was significantly higher in patients who
      had cardiac events (0.45+/-0.38 m per second per year) than those who did not
      have cardiac events (0.14+/-0.18 m per second per year, P<0.001), and the rate of
      progression of stenosis provided useful prognostic information. Of the patients
      with moderately or severely calcified aortic valves whose aortic-jet velocity
      increased by 0.3 m per second or more within one year, 79 percent underwent
      surgery or died within two years of the observed increase. CONCLUSIONS: In
      asymptomatic patients with aortic stenosis, it appears to be relatively safe to
      delay surgery until symptoms develop. However, outcomes vary widely. The presence
      of moderate or severe valvular calcification, together with a rapid increase in
      aortic-jet velocity, identifies patients with a very poor prognosis. These
      patients should be considered for early valve replacement rather than have
      surgery delayed until symptoms develop.

PMID- 10965008
TI  - Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy.
AB  - BACKGROUND: Chronic reflex sympathetic dystrophy (also called the complex
      regional pain syndrome) is a painful, disabling disorder for which there is no
      proven treatment. In observational studies, spinal cord stimulation has reduced
      the pain associated with the disorder. METHODS: We performed a randomized trial
      involving patients who had had reflex sympathetic dystrophy for at least six
      months. Thirty-six patients were assigned to receive treatment with spinal cord
      stimulation plus physical therapy, and 18 were assigned to receive physical
      therapy alone. The spinal cord stimulator was implanted only if a test
      stimulation was successful. We assessed the intensity of pain (on a visual
      analogue scale from 0 cm [no pain] to 10 cm [very severe pain]), the global
      perceived effect (on a scale from 1 [worst ever] to 7 [best ever]), functional
      status, and the health-related quality of life. RESULTS: The test stimulation of
      the spinal cord was successful in 24 patients; the other 12 patients did not
      receive implanted stimulators. In an intention-to-treat analysis, the group
      assigned to receive spinal cord stimulation plus physical therapy had a mean
      reduction of 2.4 cm in the intensity of pain at six months, as compared with an
      increase of 0.2 cm in the group assigned to receive physical therapy alone
      (P<0.001 for the comparison between the two groups). In addition, the proportion
      of patients with a score of 6 ("much improved") for the global perceived effect
      was much higher in the spinal cord stimulation group than in the control group
      (39 percent vs. 6 percent, P=0.01). There was no clinically important improvement
      in functional status. The health-related quality of life improved only in the 24
      patients who actually underwent implantation of a spinal cord stimulator. Six of
      the 24 patients had complications that required additional procedures, including
      removal of the device in 1 patient. CONCLUSIONS: In carefully selected patients
      with chronic reflex sympathetic dystrophy, electrical stimulation of the spinal
      cord can reduce pain and improve the health-related quality of life.

PMID- 10965009
TI  - Intrathecal baclofen for the treatment of dystonia in patients with reflex
      sympathetic dystrophy.
AB  - BACKGROUND AND METHODS: Patients with reflex sympathetic dystrophy (also known as
      the complex regional pain syndrome) may have dystonia, which is often
      unresponsive to treatment. Some forms of dystonia respond to the intrathecal
      administration of baclofen, a specific gamma-aminobutyric acid-receptor (type B)
      agonist that inhibits sensory input to the neurons of the spinal cord. We
      evaluated this treatment in seven women who had reflex sympathetic dystrophy with
      multifocal or generalized tonic dystonia. First, we performed a double-blind,
      randomized, controlled crossover trial of bolus intrathecal injections of 25, 50,
      and 75 microg of baclofen and placebo. Changes in the severity of dystonia were
      assessed by the woman and by an investigator after each injection. In the second
      phase of the study, six of the women received a subcutaneous pump for continuous
      intrathecal administration of baclofen and were followed for 0.5 to 3 years.
      RESULTS: In six women, bolus injections of 50 and 75 microg of baclofen resulted
      in complete or partial resolution of focal dystonia of the hands but little
      improvement in dystonia of the legs. During continuous therapy, three women
      regained normal hand function, and two of these three women regained the ability
      to walk (one only indoors). In one woman who received continuous therapy, the
      pain and violent jerks disappeared and the dystonic posturing of the arm
      decreased. In two women the spasms or restlessness of the legs decreased, without
      any change in the dystonia. CONCLUSIONS: In some patients, the dystonia
      associated with reflex sympathetic dystrophy responds markedly to intrathecal
      baclofen.

PMID- 10965010
TI  - Images in clinical medicine. Hepatodiaphragmatic interposition of the colon.

PMID- 10965011
TI  - Exercise limitation in health and disease.

PMID- 10965012
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 27-2000. A 61-year-old man with rapidly progressive dyspnea.

PMID- 10965013
TI  - Rolling back malaria in pregnancy.

PMID- 10965014
TI  - Correction: Prophylaxis against Opportunistic Infections in Patients with Human
      Immunodeficiency Virus Infection.

PMID- 10965015
TI  - Marked enhancement by fish meal of Helicobacter pylori-induced gastritis in
      Mongolian gerbils.
AB  - In a search for dietary factors influencing Helicobacter pylori-induced
      gastritis, the effects of fish meal in the diet were examined in Mongolian
      gerbils. When a conventional diet containing 10% fish meal was given to Mongolian
      gerbils for 4 weeks after inoculation of H. pylori, edematous thickening with
      severe neutrophil and mononuclear cell infiltration in both the mucosa and
      submucosa was observed in the glandular stomach of 19 out of the 20 animals, and
      hemorrhagic spots were evident in 11 cases. These gastric lesions were enhanced
      by a 20% fish meal supplement, and edema and hemorrhage in the gastric mucosa
      were observed in 19 and 17 out of 20 animals, respectively. Although almost the
      same levels of viable bacteria were detected independent of the diet, edema and
      hemorrhage were seen in only 2 and 1 of 20 gerbils fed a diet containing 10%
      casein, instead of 10% fish meal, respectively. Neither edema nor hemorrhage was
      observed in 10% beef diet animals. These results suggest that fish meal contains
      factors which greatly enhance H. pylori-induced gastritis in Mongolian gerbils.
      Since the incidences of gastritis and gastric cancer are very high throughout the
      world, it is very important to identify these gastritis-enhancing factors.

PMID- 10965016
TI  - Effect of age on the relationship between gastric cancer and Helicobacter pylori.
      Tokyo Research Group of Prevention for Gastric Cancer.
AB  - Helicobacter pylori is thought to be involved in the pathogenesis of gastric
      cancer, but the time point at which it produces its effects (critical time) is
      unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer
      patients and 1007 controls aged 20 to 69. Odds ratios for different gastric
      cancer types and stages were determined for each 10-year age class. The overall
      odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20 -
      29, 14.5 for those aged 30 - 39, 9.1 for those aged 40 - 49, 3.5 for those aged
      50 - 59, and 1.5 for those aged 60 - 69 (trend in odds ratios: P < 0.01).
      However, there was no such age-dependent trend for early diffuse-type cancer; the
      odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P = 0.29). Early
      cancer tended to show higher seroprevalence than advanced cancer, especially in
      older subjects. No significant difference in seroprevalence was observed between
      diffuse and intestinal cancers within each age-class. Seroreversion must have
      occurred in the time interval between the critical time and the diagnosis of the
      cancer, especially in older patients. The age-dependent relationship between H.
      pylori and gastric cancer may be due to seroreversion, which itself may be
      independent of age. This age-independence indicates that prolonged exposure to H.
      pylori does not increase the magnitude of its influence on gastric
      carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic
      effects are continuous inflammation in adulthood and / or irreversible damage to
      gastric mucosa in childhood or the teenage years.

PMID- 10965017
TI  - Inhibitory effects of S-methylcysteine and cysteine on the promoting potential of
      sodium phenobarbital on rat liver carcinogenesis.
AB  - The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of
      rodent hepatocarcinogenesis in a medium-term bioassay previously developed by Ito
      were examined. Initiation was induced by a single dose of diethylnitrosamine
      (DEN), followed by dietary administration of the promoter sodium phenobarbital
      (NaPB) 2 weeks later, for 6 weeks. Partial hepatectomy was conducted on all the
      animals at week 3. Inhibitory potential was evaluated by analyzing two markers of
      carcinogenesis, namely numbers of glutathione S-transferase placental form (GST
      P)-positive foci, and proliferating cell nuclear antigen (PCNA). In addition, the
      level of ornithine decarboxylase (ODC), one of the rate-limiting enzymes of
      polyamine metabolism induced by promoters, was analyzed. SMC and cysteine induced
      significant reduction in the areas of GST-P-positive foci. A significant
      reduction in the PCNA index was observed in the entire liver as well as in GST-P
      positive areas. SMC also induced down-regulation of the ODC enzyme activity.
      Thus, SMC and cysteine were found to inhibit the promotion stage of DEN-induced
      hepatocarcinogenesis. No cocarcinogenic effects were evident on administration of
      either of these chemicals with NaPB.

PMID- 10965018
TI  - Suppressive effects of dietary genistin and daidzin on rat prostate
      carcinogenesis.
AB  - High intake of phytoestrogens through soybeans and their products is thought to
      be associated with low incidences of prostate and / or breast cancer in Asian
      countries. Possible chemopreventive effects of genistin or daidzin on rat
      prostate carcinogenesis were therefore investigated. Male F344 rats were given 10
      biweekly subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and then
      either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks.
      Other groups of rats given DMAB were treated with genistin or daidzin together
      with a high dose of testosterone propionate (TP). Both genistin and daidzin
      reduced the numbers of ventral prostate carcinomas (P < 0.05), with a tendency
      for decrease in incidence. Invasive carcinomas which developed in the anterior
      prostate and seminal vesicles with TP were, however, not influenced by the two
      isoflavones. Thus, the present data suggest that genistin and daidzin possess
      anti-cancer effects at relatively early stages of prostate cancer development,
      providing experimental support for epidemiological findings.

PMID- 10965019
TI  - More frequent beta-catenin gene mutations in adenomas than in aberrant crypt foci
      or adenocarcinomas in the large intestines of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP)-treated rats.
AB  - Alteration of adenomatous polyposis coli (APC) is known to be an early event in
      neoplasia, causing activation of the beta-catenin / Tcf pathway. Although it is
      thought that alterations in APC and beta- catenin may complement one another, the
      contribution of beta-catenin mutations to colorectal carcinogenesis remains
      unclear. We therefore performed PCR-single strand conformation polymorphism
      analysis and direct sequencing of exon 3 of beta-catenin gene in adenomas,
      adenocarcinomas, and aberrant crypt foci (ACF), considered to be putative
      precursor lesions of colorectal neoplasias, in 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) treated F344 rats. beta-Catenin mutations
      were identified in all of 7 adenomas (100%) and 6 of 12 (50%) adenocarcinomas.
      All of the mutations were found in codons 32 through 34, the serine encoded by
      codon 33 being an important phosphorylation site by glycogen synthase kinase
      3beta. Regarding ACF, 14 of 46 (30.4%) were found to be mutated, eleven (78%) in
      codon 34, and the others in codon 45 (frequently altered in human colon cancer),
      and codons 47 and 56 (which have not been previously reported). The frequency of
      beta-catenin mutations in adenomas was significantly higher than in ACF (P <
      0.001) and adenocarcinomas (P < 0.05). Thus, beta-catenin mutations may have more
      importance in the genesis of adenomas than ACF or adenocarcinomas in rat colon
      carcinogens by PhIP.

PMID- 10965020
TI  - Allelic loss of the region of chromosome 1p35-pter is associated with progression
      of human gastric carcinoma.
AB  - In order to identify the region on distal chromosome 1p that is thought to
      include one or more tumor suppressor genes for gastric carcinoma, 39 gastric
      carcinomas were examined for allelic loss using 11 polymorphic microsatellite
      markers and 1 marker of single strand conformation polymorphism. Loss of
      heterozygosity (LOH) was found in 18 (46%) of 39 informative patients. The
      regions with high frequency of loss of heterozygosity were the loci at D1S548 (6
      / 17; 35.3%) and D1S2843 (7 / 20; 35%), and we found three commonly deleted
      regions on chromosome 1p35-pter. The frequency of allelic loss in the region of
      chromosome 1p35-pter was significantly associated with advanced-stage gastric
      carcinoma, but not with early-stage tumor or with the histology. These results
      suggest that allelic loss at chromosome 1p35-pter may play a role in the
      progression of gastric carcinoma.

PMID- 10965021
TI  - Preparation and characterization of antibodies against human ribosomal proteins:
      heterogeneous expression of S11 and S30 in a panel of human cancer cell lines.
AB  - Mutants of model eukaryotic organisms have revealed that most ribosomal proteins
      are essential for cell viability. However, the precise functional role of each
      ribosomal protein is largely unknown. Recent reports on the involvement of
      ribosomal proteins in various genetic diseases and studies on the extraribosomal
      functions of these proteins have cast some light on their localization and
      functions. Here we prepared rabbit polyclonal antibodies against 26 human
      ribosomal proteins; each of these reagents recognized a single band in
      immunoblots of the purified ribosome. We used these antibodies to evaluate a
      panel of human cancer cell lines. Although no deficiency of ribosomal proteins
      was observed, the abundance of S11 and S30 varied substantially among the cell
      lines, but the difference did not affect the biogenesis or composition of the
      ribosome. Therefore, the heterogeneity may be related to extraribosomal functions
      of S11 and S30. The antibodies described here are powerful tools for research
      into the molecular mechanisms of protein translation, cell-biological and medical
      studies on the ribosomal proteins, and ultimately a comprehensive understanding
      of all ribosomal proteins (rising dbl quote, left (low)ribosomics").

PMID- 10965022
TI  - Y-27632, an inhibitor of rho-associated protein kinase, suppresses tumor cell
      invasion via regulation of focal adhesion and focal adhesion kinase.
AB  - Migration of rat ascites hepatoma (MM1) cells, invasion and phagokinetic movement
      were induced by the combination of lysophosphatidic acid (LPA) and fibronectin
      (FN). Induction of migratory activity was tightly correlated with morphological
      change of MM1 cells from spherical or polygonal-shaped cells to fusiform-shaped
      ones with pseudopodia. MM1 cells were mobile in a fusiform shape, whereas those
      of a spherical or polygonal shape were not. A small GTPase Rho and one of its
      downstream effectors ROCK (Rho-associated coiled-coil forming protein kinase),
      play essential roles in these processes, as evidenced by suppression of migration
      and morphological change of MM1 cells by Clostridium botulinum C3 exoenzyme, an
      inhibitor of Rho, or by Y-27632, an inhibitor of ROCK. Y-27632 also suppressed
      the formation of fusiform-shaped pseudopodia-carrying MM1 cells that was induced
      by stimulation with the combination of LPA and FN. LPA and FN also evoked the
      formation of focal adhesions and actin bundles, and tyrosine phosphorylation of
      focal adhesion kinase (FAK) and paxillin. The inhibitory effect of Y-27632 on LPA
      induced migration and morphological change of MM1 cells was considered to be
      mediated, at least in part, by impaired formation of focal adhesions and actin
      bundles. Y-27632 suppressed LPA-induced tyrosine phosphorylation of FAK and
      paxillin, suggesting that ROCK regulates these molecules and Y-27632 inhibits
      cellular migration and morphological change, at least in part, through this
      regulation.

PMID- 10965023
TI  - Antibody-dependent cytotoxicity mediated by chimeric monoclonal antibody Nd2 and
      experimental immunotherapy for pancreatic cancer.
AB  - In a previous study, mouse monoclonal antibody (MoAb) Nd2 (m-Nd2, mouse IgG1)
      labeled with (131)I exhibited efficacy in in vivo radioimmunotherapy against
      pancreatic cancer. In this study we prepared mouse / human chimeric antibody Nd2
      (c-Nd2, human IgG1) for clinical use and examined whether c-Nd2 induced antibody
      dependent cell-mediated cytotoxicity (ADCC). Cytotoxicity to pancreatic cancer
      (PC) cell lines, including Nd2 antigen-positive (SW1990, RWP-1, Capan-1) and Nd2
      antigen-negative (Panc-1, MiaPaca-2, Capan-2) lines, was evaluated by mixed human
      leukocyte and tumor cell culture (MLTC) at an effector cell to target cell (E /
      T) ratio of 50 with or without Nd2. Cytotoxicities to SW1990 with no antibody, m
      Nd2 and c-Nd2 (1 microg / ml) were 26.7%, 38.0% and 55%, respectively; to RWP-1,
      28%, 41% and 70%; to Capan-1, 26%, 30% and 52%; to Panc-1, 24%, 28% and 30%; to
      MiaPaca-2, 18%, 20% and 27% and to Capan-2, 29. 7%, 35.0% and 40.6%. Cytotoxic
      capacity during MLTC with c-Nd2 was significantly higher than during MLTC with m
      Nd2 or with no antibody. These findings indicated that cytotoxicity to Nd2
      positive PC cells during MLTC is induced by ADCC. Intraperitoneal injection of c
      Nd2 inhibited the tumor growth of SW1990 xenografted subcutaneously in nude mice
      and prolonged the survival of nude mice in which SW1990 tumor was transplanted
      orthotopically at the tail of the pancreas. These findings suggested that,
      because of its ability to induce ADCC, c-Nd2 may be clinically useful for the
      immunotherapeutic treatment of pancreatic cancer.

PMID- 10965024
TI  - Bcl-X(L) antisense sensitizes human colon cancer cell line to 5-fluorouracil.
AB  - Resistance to 5-fluorouracil (5-FU) has been frequently found in the treatment of
      digestive tract cancer patients. Our previous study suggested that high
      expression of endogenous Bcl-X(L), might be associated with resistance to 5-FU in
      colorectal cancer. The aim of this study is to analyze the role of Bcl-X(L) in 5
      FU resistance and to explore a new therapeutic strategy using Bcl-X(L) antisense.
      First, western blot analysis shows that Bcl-X(L) rather than Bcl-2 is
      overexpressed in primary adenocarcinoma of colon. Second, when Colo320 cells,
      with undetectable endogenous Bcl-XL expression, were transfected with Bcl-XL
      gene, they acquired high resistance to 5-FU. Finally, antisense
      oligodeoxynucleotides (ODNs) that targeted the start codon of Bcl-X(L) mRNA (AS1)
      prove to be the most effective in DLD1 cells with high endogenous Bcl-X(L)
      expression. Bcl-X(L) protein expression was decreased in a dose-dependent manner
      when the cells were treated with AS1 ODNs, while non-sense and sense controls and
      5-FU had no effect on Bcl-X(L) protein. 5-FU treatment induced a level of
      apoptosis 10-fold higher in DLD1 cells than in untreated control cells, while the
      same dose of 5-FU induced a 55-fold higher level of apoptosis in DLD1 cells
      treated with Bcl-XL antisense oligodeoxynucleotides (P = 0.0003). Moreover, AS1
      ODNs coupled with 5-FU decreased viable colon cancer cells 40% more than did 5-FU
      alone (P < 0.05). These results suggest that Bcl-X(L) is an important factor for
      5-FU resistance and the suppression of Bcl-X(L) expression by the specific
      antisense ODNs can increase the sensitivity of colon cancer cells to 5-FU.

PMID- 10965025
TI  - Inhibitory effect of ATF3 antisense oligonucleotide on ectopic growth of HT29
      human colon cancer cells.
AB  - ATF3 is a transcription factor belonging to the Jun / Fos family whose mouse
      homologue (TI-241) was isolated, using the differential screening method, from
      B16 mouse melanoma cells as a blood-borne metastasis-associated gene. Here we
      show the tumorigenicity-inhibiting effect of an antisense oligonucleotide
      designed to reduce the expression of ATF3 in HT29 colon cancer cells. HT29 cells
      were reported to metastasize to the skin after intravenous inoculation. The
      antisense oligonucleotide inhibited cell attachment to the collagen-coated floor
      of the plates and invasion of HT29 cells in vitro, which are thought to be two
      important factors in the process of cancer metastasis and ectopic tumor growth.
      While the antisense oligonucleotide had no effect on cell growth of HT29 cells in
      vitro, mice that were inoculated subcutaneously with HT29 cells and treated with
      the antisense oligonucleotide survived longer than the control mice due to the
      inhibition of tumor growth in vivo. These show that ATF3 plays an important role
      in the ectopic growth / metastasis of HT29 colon cancer cells.

PMID- 10965026
TI  - TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor
      cell death.
AB  - TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent
      antitumor activity both in vitro and in vivo. In this study, we performed
      biochemical and histopathological examinations, and evaluated TZT-1027-induced
      tumoral vascular collapse and tumor cell death in an advanced tumor model, murine
      colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on
      cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT
      1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred
      mainly in the peripheral area of the tumor mass. Measurements of tumoral
      hemoglobin content and dye permeation revealed that the hemorrhage occurred
      firstly and tumor blood flow stopped secondarily. The vascular damage was
      followed by continuous induction of apoptosis of the tumor cells, tumor tissue
      necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell
      contraction with membrane blebbing in 30 min. These cell changes were completely
      inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects
      of TZT-1027 on both tumor vasculature and HUVEC were greater than those of
      vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular
      system of advanced tumors by a putative protein kinase-dependent mechanism, and
      then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional
      antitumor activity and a unique anti-tumoral vascular activity, making it a
      potentially powerful tool for clinical cancer therapy.

PMID- 10965027
TI  - In vitro plasma protein binding and cellular uptake of ATX-S10(Na), a hydrophilic
      chlorin photosensitizer.
AB  - ATX-S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum
      at 670 nm, is a candidate second-generation photosensitizer for photodynamic
      therapy (PDT) for cancer treatment. In this study, we examined plasma protein
      binding, cellular uptake and subcellular targets of ATX-S10(Na) in vitro. Protein
      binding ratios of 50 microg / ml ATX-S10(Na) in rat, dog and human plasma were
      73.0%, 87.2% and 97.7%, respectively. Gel filtration chromatography revealed that
      1 mg / ml ATX-S10(Na) bound mainly to high-density lipoprotein (HDL) and serum
      albumin at the protein concentration of 0.4%, with binding ratios of 46% and 36%,
      respectively. The free form of ATX-S10(Na) was mostly incorporated into T.Tn
      cells, and its cellular uptake was partially but significantly inhibited by
      endocytosis inhibitors such as phenylarsine oxide, chloroquine, monensin and
      phenylglyoxal, and by chilling the cells to 4 degrees C. However, ouabain,
      harmaline, sodium cyanide, probenecid and aspartic acid did not influence the
      uptake of ATX-S10(Na), suggesting that cellular uptake of ATX-S10(Na) was not
      related to sodium-potassium pump activity, sodium-dependent transporter activity,
      mitochondrial oxidative respiration, organic anion transporter activity or
      aspartic acid transporter activity. By fluorescence microscopy, lysosomal
      localization of ATX-S10(Na) was observed in T.Tn cells. However, electron
      microscopic observation revealed that many subcellular organelles such as
      mitochondria, endoplasmic reticulum, ribosomes, Golgi complex and plasma membrane
      were damaged by PDT using 25 microg / ml ATX-S10(Na) soon after laser irradiation
      at 50 J / cm(2), and tumor necrosis was rapidly induced. This result indicated
      that ATX-S10(Na) was widely distributed within the cell.

PMID- 10965028
TI  - The combined effect of electroporation and borocaptate in boron neutron capture
      therapy for murine solid tumors.
AB  - 10 B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII
      tumor-bearing C3H / He mice. Electroporation (EP) was conducted by using a
      tweezers-type electrode. The (10) B contents in tumors were measured by prompt
      gamma-ray spectrometry. The colony formation assay was applied to investigate the
      antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate
      the intratumor localization of BSH. The (10) B concentrations in tumors decreased
      with time following BSH administration, falling to 5.4(0. 1) ppm at 3 h, whereas
      EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of
      BSH from tumors, and the (10) B level remained at 19.4(0.9) ppm at 3 h. The
      effect of BNCT increased with the (10) B concentration in tumors, and the
      combination with EP showed a remarkably large cell killing effect even at 3 h
      after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell
      survival curve of tumors, without EP was proportional to tumor (10) B level (r =
      0.982), and that of BSH-BNCT combined with EP lay close to the same correlation
      line. However, tumors subjected to EP after BSH injection did not show high
      radiosensitivity when irradiated after conversion to a single cell suspension by
      enzymatic digestion. This indicates that the increase of the BNCT effect by EP
      was a consequence of enclosure of BSH in the interstitial space of tumor tissue
      and not within tumor cells. This is different from a previous in vitro study. The
      combination of EP and BNCT may be clinically useful, if a procedure to limit EP
      to the tumor region becomes available or if an alternative similar method is
      employed.

PMID- 10965029
TI  - Computed tomography during arteriography and arterial portography in small
      hepatocellular carcinoma and dysplastic nodule: a prospective study.
AB  - We studied the relationship between the findings of computed tomography during
      arteriography (CTA) and computed tomography during arterial portography (CTAP),
      and pathologic findings of 81 small nodular lesions (3 cm or less in diameter) in
      resected liver specimens. The 81 lesions consisted of 8 dysplastic nodule (DN)
      lesions, 23 well-differentiated hepatocellular carcinomas (early HCCs) and 50
      moderately or poorly differentiated HCCs (advanced HCCs). We also performed
      standard computed tomography (CT), digital subtraction angiography (DSA),
      magnetic resonance imaging (MRI), and ultrasonography, and compared sensitivities
      with CTA, CTAP, or combination of CTA and CTAP with other imaging methods. Forty
      four of the 50 advanced HCCs, 12 of the 23 early HCCs, and none of 8 DNs
      hyperattenuated with CTA and hypoattenuated with CTAP. The sensitivity for the
      early HCCs was significantly higher for CTA and CTAP in combination as compared
      with DSA or standard CT. The sensitivity for the advanced HCCs was significantly
      higher for CTA and CTAP in combination than with DSA. The sequential changes of
      the blood supply from the portal vein to the hepatic artery during the
      development of the HCCs were observed. Although CTA and CTAP in combination were
      useful for the distinction of advanced HCC from early HCC or DN, CTA and CTAP
      used in combination were not superior to CTA alone in the detection of such
      lesions.

PMID- 10965030
TI  - Molecular mimicry of human tumor antigen by heavy chain CDR3 sequence of the anti
      idiotypic antibody.
AB  - We isolated and characterized an anti-idiotype monoclonal antibody (AR42.1) which
      is capable of mimicking a distinct and specific epitope of MUC-1 antigen. The
      cDNA sequences coding for the AR42.1 variable regions were determined. We found
      significant amino acid homology between complementary determining regions 3
      (CDR3) in the heavy chain of AR42.1 and the determinant epitope sequence of MUC
      1. This 10 amino acid sequence may represent an "internal image" of the anti
      idiotype antibody to the MUC-1 antigen, and could be used for development of a
      MUC-1 surrogate for immunotherapy.

PMID- 10965031
TI  - Crystal structure of the pyridoxal 5'-phosphate dependent L-methionine gamma
      lyase from Pseudomonas putida.
AB  - L-Methionine gamma-lyase (MGL) catalyzes the pyridoxal 5'-phosphate (PLP)
      dependent alpha,gamma-elimination of L-methionine. We have determined two crystal
      structures of MGL from Pseudomonas putida using MAD (multiwavelength anomalous
      diffraction) and molecular replacement methods. The structures have been refined
      to an R-factor of 21.1% at 2.0 and 1.7 A resolution using synchrotron radiation
      diffraction data. A homotetramer with 222 symmetry is built up by non
      crystallographic symmetry. Two monomers associate to build the active dimer. The
      spatial fold of subunits, with three functionally distinct domains and their
      quarternary arrangement, is similar to those of L-cystathionine beta-lyase and L
      cystathionine gamma-synthase from Escherichia coli.

PMID- 10965032
TI  - Disulfide bonds in rat cutaneous fatty acid-binding protein.
AB  - Unlike other fatty acid-binding proteins, cutaneous (epidermal) fatty acid
      binding proteins contain a large number of cysteine residues. The status of the
      five cysteine residues in rat cutaneous fatty acid-binding protein was examined
      by chemical and mass-spectrometric analyses. Two disulfide bonds were identified,
      between Cys-67 and Cys-87, and between Cys-120 and Cys-127, though extent of
      formation of the first disulfide bond was rather low in another preparation. Cys
      43 was free cysteine. Homology modeling study of the protein indicated the close
      proximity of the sulfur atoms of these cysteine pairs, supporting the presence of
      the disulfide bonds. These disulfide bonds appear not to be directly involved in
      fatty acid-binding activity, because a recombinant rat protein expressed in
      Escherichia coli in which all five cysteines are fully reduced showed fatty acid
      binding activity as examined by displacement of a fluorescent fatty acid analog
      by long-chain fatty acids. However, the fact that the evolutionarily distant
      shark liver fatty acid-binding protein also has a disulfide bond corresponding to
      the one between Cys-120 and Cys-127, and that fatty acid-binding proteins play
      multiple roles suggests that some functions of cutaneous fatty acid-binding
      protein might be regulated by the cellular redox state through formation and
      reduction of disulfide bonds. Although we cannot completely exclude the
      possibility of oxidation during preparation and analysis, it is remarkable that a
      protein in cytosol under normally reducing conditions appears to contain
      disulfide bonds.

PMID- 10965033
TI  - States of tryptophyl residues and stability of recombinant human matrix
      metalloproteinase 7 (matrilysin) as examined by fluorescence.
AB  - States of tryptophyl residues and stability of human matrilysin were studied. The
      activation energy for the thermal inactivation of matrilysin was determined to be
      237 kJ/mol, and 50% of the activity was lost upon incubation at 69 degrees C for
      10 min. The activity was increased by adding NaCl, and was doubled with 3 M NaCl.
      Denaturation of matrilysin by guanidine hydrochloride (GdnHCl) and urea was
      monitored by fluorescence change of tryptophyl residues. Half of the change was
      observed at 2.2-2.7 M GdnHCl, whereas no change was observed even with 8 M urea.
      Half of the inactivation was induced at 0.8 M GndHCl and at 2 M urea. The
      presence of an inactive intermediate with the same fluorescence spectrum as the
      native enzyme was suggested in the denaturation. Matrilysin contains four
      tryptophyls, and their states were examined by fluorescence-quenching with iodide
      and cesium ions and acrylamide. No tryptophyls in the native enzyme were
      accessible to I(-) and Cs(+), and 2.4 residues were accessible to acrylamide.
      Based on the crystallographic study, Trp154 is water-accessible, but it should be
      in a crevice not to contact with I(-) and Cs(+). All tryptophyls in the GdnHCl
      denatured enzyme were exposed to the quenchers, while a considerable part was
      inaccessible in the urea-denatured one.

PMID- 10965034
TI  - Purification and characterization of cytochrome c-553 from Helicobacter pylori.
AB  - Helicobacter pylori, a microaerophilic Gram-negative spiral bacterium residing in
      the human stomach, contains a small size soluble cytochrome c. This cytochrome c
      was purified from the soluble fraction of H. pylori by conventional
      chromatographies involving octyl-cellulose and CM-Toyopearl. Its reduced form
      gave an alpha absorption band at 553 nm, and thus the cytochrome was named H.
      pylori cytochrome c-553. The cytochrome, giving a band below 10,000 Da upon SDS
      PAGE, was determined to have a mass of 8,998 by time of flight mass spectroscopy.
      Its N-terminal peptide sequence was TDVKALAKS---, indicating that the nascent
      polypeptide was cleaved to produce a signal peptide of 19 amino acid residues and
      a mature protein composed of 77 amino acid residues. The cb-type cytochrome c
      oxidase oxidized ferrocytochrome c-553 of this bacterium actively (V(max) of
      about 250 s(-1)) with a small K(m) (0.9 microM). Analysis of the effect of the
      salt concentration on the oxidase activity indicated that oxidation of cytochrome
      c-553 is highly inhibited under high ionic conditions. The amino acid sequence of
      H. pylori cytochrome c-553 showed the closest similarity to that of Desulfovibrio
      vulgaris cytochrome c-553, and these sequences showed a weak relationship to that
      of the cytochrome c(8)-group among class I cytochromes c.

PMID- 10965036
TI  - Molecular cloning and characterization of cDNAs encoding two isoforms of ribulose
      1,5-bisphosphate carboxylase/oxygenase activase in rice (Oryza sativa L.).
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) activase catalyzes the
      activation of RuBisCO in vivo. Two full length cDNAs designated as OsrcaA1 and
      OsrcaA2 encoding two RuBisCO activase isoforms of 47 and 43 kDa, respectively,
      have been cloned and characterized. The two isoforms were 99% identical, the 47
      kDa isoform having an additional 33 amino acids and a 5 amino acid substitution
      at the carboxyl terminus. The deduced amino acid sequences of OsrcaA1 and OsrcaA2
      showed 73-89% identity with RuBisCO activase from other higher plants. Two highly
      conserved ATP binding sites were identified. The Osrca mRNAs, and the RuBisCO
      activase proteins of 43 and 47 kDa were specifically detected in leaf, but not in
      root or etiolated seedling tissues. During leaf development, the abundance of
      Osrca mRNAs increased from the 7th to the 3rd leaf, and reached a maximum in the
      2nd leaf, although the amounts of the 43 and 47 kDa RuBisCO activase remained
      almost unchanged among the six leaves, indicating the involvement of post
      transcription control in the regulation of RuBisCO activase expression in rice.
      The co-immunoprecipitation of RuBisCO LSU and SSU with RuBisCO activase suggests
      that RuBisCO activase interacts with RuBisCO in vivo.

PMID- 10965035
TI  - Ligand-binding properties of annexin from Caenorhabditis elegans (annexin XVI,
      Nex-1).
AB  - Annexins are structurally related proteins that bind phospholipids in a calcium
      dependent manner. Recently, we showed that annexins IV, V, and VI also bind
      glycosaminoglycans in a calcium-dependent manner. Annexins are widely distributed
      from lower to higher eukaryotes, and the nematode Caenorhabditis elegans has been
      found to contain Nex-1, an annexin homologue. Here, we characterize the ligand
      binding properties of Nex-1 using recombinant Nex-1. Nex-1 binds to liposomes
      containing phosphatidylserine. The apparent K(d) was calculated by Biacore to be
      4.4 nM. Compared to mammalian annexins, the Nex-1 phospholipid-binding
      specificities were similar whereas the K(d) values were one order of magnitude
      larger. The Nex-1 glycosaminoglycan-binding specificities were investigated by
      affinity chromatography and solid-phase assays. Nex-1 binds to heparin, heparan
      sulfate, and chondroitin sulfate but not to chondroitin and chemically N- or O
      desulfated heparin. Besides phospholipids, heparan sulfate and/or chondroitin
      (sulfate), probably on perlecan, could be endogenous ligands of Nex-1.

PMID- 10965037
TI  - Characterization of L-lysine 6-aminotransferase and its structural gene from
      Flavobacterium lutescens IFO3084.
AB  - L-Lysine 6-aminotransferase (LAT) is an enzyme involved in L-lysine catabolism in
      a wide range of living organisms. LAT from Flavobacterium lutescens IFO3084 was
      purified, and its structural gene (lat) was cloned, sequenced and expressed in
      Escherichia coli. Native PAGE analysis of purified LAT gave a single band
      corresponding to a molecular weight of about 110,000. lat encoded a protein of
      493 amino acids with a deduced molecular weight of 53,200, which is very close to
      that of purified LAT determined on SDS-PAGE. Expression of lat in E. coli
      revealed that lat encodes a single subunit protein leading to LAT activity. These
      data suggested that LAT from F. lutescens IFO3084, like most other
      aminotransferases, is derived from a single ORF and is active as a homodimer.

PMID- 10965038
TI  - A subunit of the mammalian oligosaccharyltransferase, DAD1, interacts with Mcl-1,
      one of the bcl-2 protein family.
AB  - DAD1 is a mammalian homologue of Saccharomyces cerevisiae Ost2p, a subunit of the
      oligosaccharyltransferase complex. Loss of its function induces apoptosis in
      hamster BHK21 cells. By means of a two-hybrid method involving DAD1 as bait, the
      C-terminal region of Mcl-1, one of the bcl-2 family, was isolated. Consistently,
      DAD1 binds well to Mcl-1 in COS cells when overexpressed. On deletion analysis,
      the C-terminal domain of Mcl-1 containing BH(2) (bcl-2 homologous domain) was
      found to be essential for the interaction with DAD1. On the other hand, the C
      terminal half of DAD1 was concluded to be essential for the interaction with Mcl
      1. Surprisingly, a DeltaC-DAD1 mutant lacking only 4 amino acid residues from the
      C-terminus did not complement the tsBN7 mutation, while it interacted well with
      Mcl-1. In contrast, DeltaN-DAD1 lacking 20 amino acid residues from the N
      terminus still exhibited the ability to complement the tsBN7 mutation. Thus, the
      C-terminus of DAD1 was suggested to play an important role in N-linked
      glycosylation and to complement the tsBN7 mutation. Mcl-1 may be required for the
      inhibition of apoptotic cell death caused by a loss of DAD1.

PMID- 10965039
TI  - Two distinct mechanisms underlie the stimulation of neurotransmitter release by
      phorbol esters in clonal rat pheochromocytoma PC12 cells.
AB  - Phorbol ester treatment induces the phosphorylation of SNAP-25 at Ser(187) and
      the potentiation of Ca(2+)-induced dopamine (DA) and acetylcholine (Ach) release
      from PC12 cells. In order to evaluate the functional consequences of
      phosphorylation, quantitative analysis was carried out using an anti
      phosphopeptide antibody that specifically recognizes SNAP-25 phosphorylated at
      Ser(187). DA and ACh release, assayed in low-K(+) as well as high-K(+) solution,
      increased by treating the cells with phorbol-12-myristate-13-acetate (PMA);
      however, the stimulation of high-K(+)-dependent release occurred at lower
      concentrations and with shorter exposures to PMA than that of the basal release
      in low-K(+)-solution. The PMA-induced phosphorylation of SNAP-25 did not
      correlate with the potentiation of high-K(+)-dependent neurotransmitter release.
      The potentiation of high-K(+)-dependent DA release by phorbol 12,13-diacetate
      (PDA), a water soluble phorbol ester, almost completely disappeared within 1 min
      after washing PDA in the presence of okadaic acid, conditions under which the
      phosphorylation of SNAP-25 persisted for at least 15 min. PMA-induced
      phosphorylation of SNAP-25 was inhibited by staurosporine, however, the
      potentiation of high-K(+)-dependent DA release was suppressed only partially.
      These results indicate that protein kinase activation does not account for a
      large fraction of the phorbol ester-induced potentiation of depolarization
      dependent neurotransmitter release from PC12 cells.

PMID- 10965040
TI  - Substrate specificity analysis of microbial transglutaminase using proteinaceous
      protease inhibitors as natural model substrates.
AB  - The substrate specificity of microbial transglutaminase (MTG) from Streptomyces
      mobaraensis (formerly categorized Streptoverticillium) was studied using a
      Streptomyces proteinaceous protease inhibitor, STI2, as a model amine-donor
      substrate. Chemical modification and mutational analysis to address the substrate
      requirements for MTG were carried out around the putative reactive site region of
      STI2 on the basis of the highly refined tertiary structure and the solvent
      accessibility index of Streptomyces subtilisin inhibitor, SSI, a homolog of STI2.
      The results suggest that the P1 reactive center site (position 70 of STI2) for
      protease subtilisin BPN' or trypsin may be the prime Lys residue that can be
      recognized by MTG, when succinylated beta-casein was used as a partner Gln
      substrate. It is characteristic in that the same primary enzyme contact region of
      STI2 is shared by both enzymes, MTG and proteases. For quantitative analysis of
      the TG reaction, we established an ELISA-based monitoring assay system using an
      anti-SSI polyclonal antibody highly cross-reactive with STI2. Site-specific STI2
      mutants were prepared by an Escherichia coli expression-secretion vector system
      and subjected to the assay system. We reached several conclusions concerning the
      nature of the flanking amino acid residues affecting the MTG reactivity of the
      substrate Lys residue: (i) site-specific mutations from Asn to Lys or Arg at
      position 69 preceding the amine-donor 70Lys, led to enhanced substrate
      reactivity; (ii) amino acid replacement at 67Ile with Ser led to higher substrate
      reactivity, (iii) additive effects were obtained by a combination of the positive
      mutations at positions 67 and 69 as described above, and (iv) Gly at position 65
      might be essential for MTG reaction. Moreover, the substrate specificity of
      guinea pig liver tissue transglutaminase (GTG) was compared with that of MTG
      using STI2 and its mutants. In contrast to MTG, replacement of Gly by Asp at
      position 65 was the most favorable for substrate reactivity. Also, 70Lys appeared
      not to be a prime amine-donor site for GTG-mediated cross-linking, suggesting a
      difference in substrate recognition between MTG and GTG.

PMID- 10965041
TI  - Differential expression of mouse alpha5(IV) and alpha6(IV) collagen genes in
      epithelial basement membranes.
AB  - We first completed the primary structure of the mouse alpha5(IV) and alpha6(IV)
      chains, from which synthetic peptides were produced and a chain-specific
      monoclonal antibodies were raised. Expression of collagen IV genes in various
      basement membranes underlying specific organ epithelia was analyzed by
      immunohistochemical staining using these monoclonal antibodies and other
      antibodies from human and bovine sequences. It was possible to predict the
      presence of the three collagen IV molecules: [alpha1(IV)](2) alpha2(IV),
      alpha3(IV)alpha4(IV)alpha5(IV), and [alpha5(IV)](2)alpha6(IV). In skin basement
      membrane two of the three forms, [alpha1(IV)](2)alpha2(IV) and
      [alpha5(IV)](2)alpha6(IV), were detected. The alpha3(IV)alpha4(IV)alpha5(IV)
      molecule was observed as the major form in glomerulus, alveolus, and choroid
      plexus, where basement membranes function as filtering units. The molecular form
      [alpha5(IV)](2)alpha6(IV) was present in basement membranes in tubular organs
      such as the epididymis, where the tubes need to expand in diameter. Thus, the
      distribution of the basement membranes with different molecular composition is
      consistent with tissue-specific function.

PMID- 10965042
TI  - Activation of actin-activated MgATPase activity of myosin II by phosphorylation
      with MAPK-activated protein kinase-1b (RSK-2).
AB  - Regulatory light chain of myosin II (MRLC) was identified as a novel substrate of
      p90 ribosomal S6 kinase (RSK)-2, a Ser/Thr protein kinase which is phosphorylated
      and activated by mitogen-activated protein kinase (MAPK) in vitro and in vivo.
      Phosphopeptide map of MRLC phosphorylated by RSK-2 was identical to that by
      myosin light chain kinase (MLCK). Phosphoserine was recovered by the phosphoamino
      acid analysis of MRLC phosphorylated by RSK-2. Further, phosphorylation using
      recombinant glutathione S-transferase (GST) fusion proteins of HeLa MRLC2
      revealed that RSK-2 phosphorylated wild-type MRLC2 (GST-wtMRLC2) but not its
      mutants GST-MRLC2(S19A) or GST-MRLC2(T18AS19A) (alanine substituted for Ser19 or
      both Ser19 and Thr18). These results revealed that RSK-2 phosphorylates MRLC at
      Ser19 as did MLCK. Phosphorylation of myosin II by RSK-2 resulted in activation
      of actin-activated MgATPase activity of myosin II. Interestingly, RSK-2 activity
      to phosphorylate MRLC was suppressed by phosphorylation with MAPK. RSK-2 might be
      a mediator that regulates myosin II activity through the MAPK cascade.

PMID- 10965044
TI  - Modulation of the peptide-binding specificity of a single-chain class II major
      histocompatibility complex.
AB  - We designed and expressed a single-chain class II major histocompatibility
      complex molecule capable of forming a stable complex with an antigenic peptide.
      The peptide-binding preference of the single-chain (sc) human leukocyte antigen
      derived from DRB5(*)0101 (DR51) was determined to be similar to that of the
      authentic one, which requires a bulky hydrophobic residue at position-1 (P1) as a
      primary anchor. For modulation of the peptide-binding affinity, we modified
      binding pocket 1 of sc DR51 by site-directed mutagenesis. The relative binding
      affinity of the engineered sc DR51 for several P1-substituted peptides was
      measured by competition assaying with a fluorescence labeled peptide. The sc DR51
      molecule showed high affinity to the self-peptide derived from myelin basic
      protein, 87-98 with Phe as the P1 residue (F90F). While reduction of pocket 1
      volume (betaG86V) decreased the affinity of F90F, it rather increased the
      affinity of the Ala-substituted peptide as to the P1 residue (F90A). Through more
      extensive engineering in the peptide-binding groove of the sc DR51 molecule, it
      is expected that we can construct sc DR51 variants with various peptide ligand
      motifs.

PMID- 10965043
TI  - Directed evolution to improve the thermostability of prolyl endopeptidase.
AB  - Prolyl endopeptidase is the only endopeptidase that specifically cleaves peptides
      at proline residues. Although this unique specificity is advantageous for
      application in protein chemistry, the stability of the enzyme is lower than those
      of commonly used peptidases such as subtilisin and trypsin. Therefore, we
      attempted to apply a directed evolution system to improve the thermostability of
      the enzyme. First, an efficient expression system for the enzyme in Escherichia
      coli was established using the prolyl endopeptidase gene from Flavobacterium
      meningosepticum. Then, a method for screening thermostable variants was developed
      by combining heat treatment with active staining on membrane filters. Random
      mutagenesis by error-prone PCR and screening was repeated three times, and as a
      result the thermostability of the enzyme was increased step by step as the amino
      acid substitutions accumulated. The most thermostable mutant obtained after the
      third cycle, PEP-407, showed a half-life of 42 min at 60 degrees C, which was 60
      times longer than that of the wild-type enzyme. The thermostable mutant was also
      more stable with a high concentration of glycerol, which is a necessary condition
      for in vitro amidation.

PMID- 10965045
TI  - Synthesis of a molt-inhibiting hormone of the American crayfish, Procambarus
      clarkii, and determination of the location of its disulfide linkages.
AB  - A molt-inhibiting hormone (Prc-MIH) of the American crayfish, Procambarus
      clarkii, a member of the type II CHH family, was chemically synthesized and the
      location of its three disulfide linkages was determined. Prc-MIH consists of 75
      amino acid residues and was synthesized by a thioester method. Two peptide
      segments, Boc-[Cys(Acm)(7,24,27), Lys(Boc)(19)]-Prc-MIH(1-39)-SCH(2)CH(2)CO-Nle
      NH(2) and H-[Cys(Acm)(40,44,53), Lys(Boc)(42,51,67)]-Prc-MIH(40-75)-NH(2), were
      prepared using peptides obtained via the Boc solid-phase method. Condensation of
      the building blocks in the presence of silver chloride, 3,4-dihydro-3-hydroxy-4
      oxo-1,2,3-benzotriazine, and N, N-diisopropylethylamine, followed by removal of
      the protecting groups, gave the reduced form of Prc-MIH(1-75)-NH(2). This product
      was converted to the native form of Prc-MIH (synthetic Prc-MIH) in a buffer which
      contained cysteine and cystine. The synthetic Prc-MIH showed the same behavior by
      RP-HPLC and biological activity assays as the natural Prc-MIH. The disulfide bond
      between Cys7 and Cys44 was determined by isolation of a fragment from an
      enzymatic digest of the synthetic Prc-MIH by RP-HPLC, followed by mass analysis.
      The disulfide bonds between Cys24 and Cys40 and between Cys27 and Cys53 were
      determined by comparing the elution position of an enzymatic digest of the
      synthetic Prc-MIH with authentic chemically synthesized samples, which contained
      three types of possible disulfide linkages.

PMID- 10965046
TI  - Depletion of intracellular NAD(+) and ATP levels during ricin-induced apoptosis
      through the specific ribosomal inactivation results in the cytolysis of U937
      cells.
AB  - Our previous studies demonstrated that ricin induces the apoptotic death of U937
      cells as evidenced by DNA fragmentation, nuclear morphological changes, and
      increases in caspase-like activities. In this study, we have found that
      intracellular NAD(+) and ATP levels decrease in ricin-treated U937 cells and that
      this decrease is followed by the ricin-mediated protein synthesis inhibition. The
      PARP inhibitor, 3-aminobenzamide (3-ABA), prevents the depletion in NAD(+) and
      ATP levels and concomitantly protects U937 cells from the lysis that follows
      ricin treatment. Hence, the protective action of 3-ABA is due to the inhibition
      of PARP and does not result from its other pharmacological side effects.
      Moreover, the enzymatic activity of PARP gradually increases and reaches a
      maximum level after ricin exposure for 3 h, whereas no significant change in
      activity was observed in untreated cells. However, 3-ABA has no effect on ricin
      mediated DNA fragmentation. In addition, immunoblot analysis revealed that
      significant PARP cleavage occurred more than 12 h after ricin addition, while DNA
      fragmentation reached a maximum level within 6 h of incubation. Thus, in the case
      of ricin-induced apoptosis, it appears that PARP cleavage is not an early
      apoptotic event associated with the onset of apoptosis. Our results suggest that
      multiple apoptotic signaling pathways may be triggered by ricin-treatment.
      Probably, the pathway leading to cell lysis via PARP activation and NAD(+)
      depletion is independent of the pathway leading to DNA fragmentation in which
      caspases may be profoundly involved. Other protein synthesis inhibitors,
      including diphtheria toxin and cycloheximide, were less effective in terms of
      inducing DNA fragmentation and cytolysis, even at concentrations that cause
      significant inhibition of protein synthesis. Thus, a specific ricin action
      mechanism through which ribosomes are inactivated may be responsible for the
      apoptotic events induced by ricin.

PMID- 10965047
TI  - Three leucine-rich sequences and the N-terminal region of double-stranded RNA
      activated protein kinase (PKR) are responsible for its cytoplasmic localization.
AB  - The double-stranded RNA-activated-protein kinase PKR was originally identified as
      a ribosomal protein that regulates protein synthesis at the translational level.
      While PKR locates predominantly to the cytoplasm, nuclear or nucleolar species of
      PKR have been detected. Here, we demonstrate that PKR possesses three leucine
      rich sequences resembling nuclear export signals (NESs). Enhanced green
      fluorescent protein (EGFP) fused to one of these sequences and transfected in COS
      1 cells exhibited predominant cytoplasmic staining, which was abrogated by a
      leucine to alanine substitution. In addition, Leptomycin B (LMB), an inhibitor of
      NES-mediated nuclear export, inhibited the cytoplasmic localization of EGFP-NES,
      indicating the potential activity of these stretches as NESs. Although EGFP fused
      to a PKR with three NES mutations still located to the cytoplasm, an additional N
      terminal deletion impaired the cytoplasmic predominance, suggesting that the N
      terminal region is also required for localization. These results suggest that the
      cytoplasmic localization of PKR is regulated by NESs as well as the N-terminal
      sequence.

PMID- 10965048
TI  - Manganese administration induces the increased production of dopamine sulfate and
      depletion of dopamine in Sprague-Dawley rats.
AB  - Sprague-Dawley rats were used as an experimental model for investigating the
      effects of manganese poisoning on the serum levels of unsulfated and sulfated
      forms of dopamine and its biosynthetic precursors, L-Dopa and L-p-tyrosine.
      Groups of rats were treated daily with Mn(2+) (20 mg or 40 mg; in the form of
      MnSO(4)) or Na(+) (20 mg; in the form of Na(2)SO(4)). High performance liquid
      chromatography (HPLC) analysis of the serum samples taken after a 50-day
      experimental period revealed that the serum level of dopamine sulfate increased
      by more than 10 times compared with untreated control rats or rats treated with
      sodium sulfate. In contrast, there was a dramatic decrease (by as much as 4.8
      times) in the serum level of unsulfated dopamine in manganese-treated rats. The
      serum levels of L-Dopa sulfate and L-p-tyrosine sulfate were also markedly
      elevated, although not as much as those of dopamine sulfate. Meanwhile, the serum
      levels of unsulfated L-Dopa and L-p-tyrosine showed no dramatic changes. Atomic
      absorption spectrophotometric analysis revealed in general an accumulation of
      manganese in the four organ samples taken from manganese-treated rats. Compared
      with liver, heart, and kidney, the highest degree of manganese accumulation in
      manganese-treated rats appeared to be in brain. These results together suggested
      a role for manganese in stimulating the dopamine-sulfating sulfotransferases in
      brain, thereby leading to the depletion of dopamine in vivo.

PMID- 10965049
TI  - Common architecture of the primary galactose binding sites of Erythrina
      corallodendron lectin and heat-labile enterotoxin from Escherichia coli in
      relation to the binding of branched neolactohexaosylceramide.
AB  - The heat-labile enterotoxin from Escherichia coli (LT) is responsible for so
      called traveller's diarrhea and is closely related to the cholera toxin (CT).
      Toxin binding to GM1 at the epithelial cell surface of the small intestine
      initiates the subsequent diarrheal disease. However, LT has a broader receptor
      specificity than CT in that it also binds to N-acetyllactosamine-terminated
      structures. The unrelated lectin from Erythrina corallodendron (ECorL) shares
      this latter binding property. The findings that both ECorL and porcine LT (pLT)
      bind to lactose as well as to neolactotetraosylceramide suggests a common
      structural theme in their respective primary binding sites. Superimposing the
      terminal galactose of the lactoses in the respective crystal structures of pLT
      and ECorL reveals striking structural similarities around the galactose despite
      the lack of sequence and folding homology, whereas the interactions of the
      penultimate GlcNAcb3 in the neolactotetraosylceramide differ. The binding of
      branched neolactohexaosylceramide to either protein reveals an enhanced affinity
      relative to neolactotetraosylceramide. The b3-linked branch is found to bind to
      the primary Gal binding pocket of both proteins, whereas the b6-linked branch
      outside this site provides additional interactions in accordance with the higher
      binding affinities found for this compound. While the remarkable architectural
      similarities of the primary galactose binding sites of pLT and ECorL point to a
      convergent evolution of these subsites, the distinguishing structural features
      determining the overall carbohydrate specificities are located in extended
      binding site regions. In pLT, Arg13 is thus found to play a crucial role in
      enhancing the affinity not only for N-acetyllactosamine-terminated structures but
      also for GM1 as compared to human LT (hLT) and CT. The physiological relevance of
      the binding of N-acetyllactosamine-containing glycoconjugates to LT and ECorL is
      briefly discussed.

PMID- 10965051
TI  - Subsite preferences of pepstatin-insensitive carboxyl proteinases from
      prokaryotes: kumamolysin, a thermostable pepstatin-insensitive carboxyl
      proteinase.
AB  - Kumamolysin, a carboxyl proteinase from Bacillus novosp. MN-32, is characterized
      by its thermostability and insensitivity to aspartic proteinase inhibitors such
      as pepstatin, diazoacetyl-DL-norleucine methylester, and 1,2-epoxy-3-(p-nitro
      phenoxy)propane. Here, its substrate specificity was elucidated using two series
      of synthetic chromogenic substrates: P(5)-P(4)-P(3)-P(2)-Phe*Nph (p
      nitrophenylalanine: *cleavage site)-P(2)'-P(3)', in which the amino acid residues
      at the P(5)-P(2), P(2)' and P(3)' positions were systematically substituted.
      Among 74 substrates, kumamolysin was shown to hydrolyze Lys-Pro-Ile-Pro-Phe-Nph
      Arg-Leu most effectively. The kinetic parameters of this peptide were K(m) = 41+/
      5 microM, k(cat) = 176+/- 10 s(-1), and k(cat)/K(m) = 4.3+/-0.6 mM(-1) x s(-1).
      These systematic analyses revealed the following features: (i) Kumamolysin had a
      unique preference for the P(2) position. Kumamolysin preferentially hydrolyzed
      peptides having an Ala or Pro residue at the P(2) position; this was also
      observed for the pepstatin-insensitive carboxyl proteinase from Bacillus
      coagulans J-4 [J-4; Shibata et al. (1998) J. Biochem. 124, 642-647]. Other
      carboxyl proteinases, including Pseudomonas sp. 101 pepstatin-insensitive
      carboxyl proteinase (PCP) and Xanthomonas sp. T-22 pepstatin-insensitive carboxyl
      proteinase (XCP), preferred peptides having hydrophobic and bulky amino acid
      residue such as Leu at the P(2) position. (ii) Kumamolysin preferred such charged
      amino acid residues as Glu or Arg at the P(2)' position, suggesting that the
      S(2)' subsite of kumamolysin is occupied by hydrophilic residues, similar to that
      of PCP, XCP, and J-4. In general, the S(2)' subsite of pepstatin-sensitive
      carboxyl proteinases (aspartic proteinases) is hydrophobic in nature. Thus, the
      hydrophilic nature of the S(2)' subsite was confirmed to be a distinguishing
      feature of pepstatin-insensitive carboxyl proteinases from prokaryotes.

PMID- 10965050
TI  - Protein N-arginine methylation in subcellular fractions of lymphoblastoid cells.
AB  - Arginine methylation in RNA-binding proteins containing arginine- and glycine
      rich RGG motifs is catalyzed by specific protein arginine N-methyltransferase in
      cells. We previously showed that lymphoblastoid cells grown in the presence of an
      indirect methyltransferase inhibitor, adenosine dialdehyde (AdOx), accumulated
      high level of hypomethylated protein substrates for the endogenous protein
      methyltransferases or recombinant yeast arginine methyltransferase [Li, C. et al.
      (1998) Arch. Biochem. Biophys. 351, 53-59]. In this study we fractionated the
      lymphoblastoid cells to locate the methyltransferases and the substrates in
      cells. Different sets of hypomethylated methyl-accepting polypeptides with wide
      range of molecular masses were present in cytosolic, ribosomal, and nucleus
      fractions. The methylated amino acid residues of the methyl-accepting proteins in
      these fractions were determined. In all three fractions, dimethylarginine was the
      most abundant methylated amino acid. The protein-arginine methyltransferase
      activities in the three fractions were analyzed using recombinant fibrillarin (a
      nucleolar RGG protein) as the methyl-accepting substrate. Fibrillarin methylation
      was strongest in the presence of the cytosolic fraction, followed by the
      ribosomal and then the nucleus fractions. The results demonstrated that protein
      arginine methyltransferases as well as their methyl-accepting substrates were
      widely distributed in different subcellular fractions of lymphoblastoid cells.

PMID- 10965052
TI  - Tripeptidyl peptidase I, the late infantile neuronal ceroid lipofuscinosis gene
      product, initiates the lysosomal degradation of subunit c of ATP synthase.
AB  - The specific accumulation of a hydrophobic protein, subunit c of ATP synthase, in
      lysosomes from the cells of patients with the late infantile form of NCL (LINCL)
      is caused by a defect in the CLN2 gene product, tripeptidyl peptidase I (TPP-I).
      The data here show that TPP-I is involved in the initial degradation of subunit c
      in lysosomes and suggest that its absence leads directly to the lysosomal
      accumulation of subunit c. The inclusion of a specific inhibitor of TPP-I, Ala
      Ala-Phe-chloromethylketone (AAF-CMK), in the culture medium of normal fibroblasts
      induced the lysosomal accumulation of subunit c. In an in vitro incubation
      experiment the addition of AAF-CMK to mitochondrial-lysosomal fractions from
      normal cells inhibited the proteolysis of subunit c, but not the b-subunit of ATP
      synthase. The use of two antibodies that recognize the aminoterminal and the
      middle portion of subunit c revealed that the subunit underwent aminoterminal
      proteolysis, when TPP-I, purified from rat spleen, was added to the mitochondrial
      fractions. The addition of both purified TPP-I and the soluble lysosomal
      fractions, which contain various proteinases, to the mitochondrial fractions
      resulted in rapid degradation of the entire molecule of subunit c, whereas the
      degradation of subunit c was markedly delayed through the specific inhibition of
      TPP-I in lysosomal extracts by AAF-CMK. The stable subunit c in the mitochondrial
      lysosomal fractions from cells of a patient with LINCL was degraded on incubation
      with purified TPP-I. The presence of TPP-I led to the sequential cleavage of
      tripeptides from the N-terminus of the peptide corresponding to the amino
      terminal sequence of subunit c.

PMID- 10965054
TI  - Production of three distinct mRNAs of 150 kDa oxygen-regulated protein (ORP150)
      by alternative promoters: preferential induction of one species under stress
      conditions.
AB  - 150 kDa oxygen-regulated protein (ORP150) is one of the endoplasmic reticulum
      (ER)-resident stress proteins. We have cloned and sequenced the entire human
      ORP150 gene covering over 15-kb. Analyses of transcription initiation sites and
      transcriptional regulatory sequences revealed that at least three distinct mRNA
      species were produced by alternative promoters: two of them starting from
      alternative exon 1 (1A or 1B), and the third one starting from exon 2, six
      nucleotides upstream of the first AUG initiation codon. Among them, the
      transcript that begins with exon 1B was preferentially induced by hypoxia or
      tunicamycin treatment. A cis-acting segment involved in the stress-dependent
      induction was found at the 5'-end of exon 1A, which could account for the
      selective induction of the transcription from exon 1B. Furthermore, in vitro
      analyses of translation of the third mRNA suggested the constitutive expression
      of the cytosolic ORP150 due to the lack of the signal peptide resulting from
      differential translation initiation.

PMID- 10965055
TI  - Hydrolysis and synthesis of substrate proteins for cathepsin L in the brain
      basement membranes of Sarcophaga during metamorphosis.
AB  - Previously, we identified two proteins with molecular masses of 200 and 210 kDa
      in basement membranes of Sarcophaga imaginal discs as substrates for cathepsin L
      [Homma, K. and Natori, S. (1996) Eur. J. Biochem. 240, 443-447]. Here we
      demonstrated that the same proteins were also present in the basement membranes
      of larval brains. These proteins were suggested to be digested by cathepsin L
      secreted from the larval brains in response to 20-HE. From the behavior of these
      proteins during metamorphosis, we concluded that the basement membranes of larval
      brains are degraded at the early pupal stage and synthesized again at the late
      pupal stage, coinciding with the timing of brain remodeling that takes place
      during metamorphosis. Possibly, the transient disappearance of the basement
      membranes makes brain remodeling easier, and cathepsin L is suggested to play a
      crucial role in the degradation of the basement membranes.

PMID- 10965053
TI  - Transcriptional regulation of the human FTZ-F1 gene encoding Ad4BP/SF-1.
AB  - Ad4BP, also known as SF-1, is a steroidogenic tissue-specific transcription
      factor that is also essential for adrenal and gonadal development. Two mechanisms
      for the transcriptional regulation of the mammalian FTZ-F1 gene encoding Ad4BP in
      adrenocortical cells have been proposed in the previous studies: the crucial role
      of a cis-element, an E box for the steroidogenic cell-specific expression of
      mouse and rat FTZ-F1 genes, and a possible autoregulatory mechanism of the rFTZ
      F1 gene by Ad4BP itself through binding to the Ad4 (or SF-1) site in the first
      intron. In the present study, the transcriptional regulation of the human FTZ-F1
      gene in adrenocortical cells was investigated from several angles, including the
      above two mechanisms. Using a series of deletion analyses of the 5'-flanking
      region of the hFTZ-F1 gene and site-directed mutagenesis for transient
      transfection studies, an E box element, CACGTG at -87/-82 from the
      transcriptional start site, was also found to be essential for the transcription
      of the hFTZ-F1 gene in mouse or human adrenocortical cell lines as well as in non
      steroidogenic CV-1 cells. Despite the presence of a corresponding Ad4 site,
      CCAAGGCC at +163/+156 in the first intron of the hFTZ-F1 gene, an autoregulatory
      mechanism through the Ad4 site was found to be unlikely in the hFTZ-F1 gene
      mainly due to site-directed mutagenesis. In addition, the forced expression of
      Ad4BP had little effect on hFTZ-F1 gene transcription in non-steroidogenic CV-1
      cells. Such Ad4BP-independent regulation of the hFTZ-F1 gene was in striking
      contrast to the regulation of steroidogenic CYP genes, such as the human CYP11A
      gene, in which the proximal promoter activity is Ad4BP-dependent and the
      transactivation by Ad4BP is silenced by DAX-1. Even though the Ad4BP-dependent
      transcriptional regulation of the DAX-1 gene has been reported, DAX-1 did not
      affect the transcriptional activity of the hFTZ-F1 gene in our study. Taken
      together, these observations suggest that the E box is indeed required for the
      expression of the FTZ-F1 gene, at least in mammalian species, but may not
      determine the tissue-specific expression of the hFTZ-F1 gene, and that, unlike
      the steroidogenic CYP gene, the regulation of the hFTZ-F1 gene appears to be
      independent of both Ad4BP and DAX-1.

PMID- 10965056
TI  - Psychoimmune neuroendocrine integrative mechanisms revisited.
AB  - This review analyzes recent publications on the topic of psycho-immune
      neuroendocrine integrative mechanisms. Results on the role of cytokines in
      cognitive processes and in a major neuroendocrine event, i.e. the release of
      gonadotropin-releasing hormone, are discussed, as are the effects of cytokines on
      central neurotransmission. The control of immune responses by local sympathetic
      nerves, a major pathway in neuroimmune communication, is discussed. This review
      also updates information indicating that melatonin is a circulating signal
      affecting the periodic organization of the immune response.

PMID- 10965057
TI  - Molecular cloning of guinea pig angiotensin type 1 receptor.
AB  - The primary structure of cDNA encoding of the angiotensin type 1 receptor
      (AT(1)R) was cloned from guinea pig liver. Guinea pig AT(1)R (GP-AT(1)R) cDNA
      clone contains a 1,077-bp open reading frame which encodes a protein consisting
      of 359 amino acid residues. GP-AT(1)R amino acid sequence showed a 92% level of
      identity among mammalian species. GP-AT(1)R is expressed in liver, kidney,
      adrenal gland, heart and colon.

PMID- 10965058
TI  - Immunoglobulin G1 Fc fragment-tagged human opioid receptor-like receptor retains
      the ability to inhibit cAMP accumulation.
AB  - The human opioid receptor-like (ORL(1)) receptor was tagged with the
      immunoglobulin G1 Fc fragment at the carboxy-terminus and expressed in human
      embryonic kidney 293 cells. Expression of the ORL(1)-Fc receptor was confirmed by
      immunohistochemical staining. The fusion protein was enriched by affinity
      chromatography and then verified by immunodetection. The function of the ORL(1)
      Fc receptor was determined by examining nociceptin/OFQ-induced inhibition of cAMP
      accumulation. The ORL(1)-Fc receptor inhibited the forskolin-stimulated cAMP
      accumulation. The inhibitory response was selectively induced by nociceptin/OFQ
      in a dose-dependent and pertussis toxin-sensitive manner. Our results indicate
      that the carboxy-terminal Fc-tagged ORL(1) receptor retained the ability to
      interact with G(i) proteins to inhibit adenylyl cyclase.

PMID- 10965059
TI  - Presumptive mediators of growth hormone action on insulin-like growth factor I
      release by porcine ovarian granulosa cells.
AB  - The role of cAMP/protein kinase A (PKA)- and tyrosine kinase (TK)-dependent
      intracellular mechanisms in mediating the action of porcine growth hormone (GH)
      on insulin-like growth factor I (IGF-I) secretion by porcine ovarian granulosa
      cells was studied. It was observed that GH-induced stimulation of IGF-I secretion
      was accompanied by an increase in cAMP production. The stimulation of PKA by the
      addition of either a cAMP agonist or a phosphodiesterase inhibitor to the medium
      increased IGF-I release by the cells, indicating a direct stimulation of IGF-I
      release by cyclic nucleotides. Moreover, the stimulatory effect of GH on IGF-I
      was completely suppressed by the addition of the PKA blocker Rp-cAMPS. Neither TK
      blocker altered the basal IGF-I level, but both strongly suppressed the GH
      induced increase in IGF-I accumulation. Taken together, these findings suggest
      that cAMP/PKA- and/or TK-dependent pathways may be involved in the mediation of
      GH action on IGF-I release by porcine granulosa cells.

PMID- 10965061
TI  - Melatonin and melanocyte functions.
AB  - The effect of melatonin on melanocyte functions was studied by incubating whole
      skin organ cultures with melatonin, as well as by assessing melatonin positivity
      in melanocytes versus dendricity and pigmentation, when arrested in the G(2)
      phase. From this study, it was observed that melatonin positivity is inversely
      related to the length of UV exposure. Increasing melatonin levels are related to
      decreasing dendricity and pigment donation during photoresponse in the G(2)
      phase. Melanocyte melatonin positivity increases with dark incubation and is
      higher with a pulse of UV exposure after dark incubation with melatonin. This
      increase is associated with a doubling of melanocyte number after dark incubation
      and a further doubling upon exposure to a pulse of UV. The melanocytes directly
      take up melatonin, which results in a marked increase in their numbers. Thus,
      extreme caution should be exercised when using melatonin as an anticancer drug.
      This finding also simulates the melanocyte repopulation of the skin with
      repigmentation during summer in polar animals.

PMID- 10965060
TI  - Effects of somatostatin and its analogues on tyrosine kinase activity in rodent
      tumors.
AB  - The effects of native somatostatin-14 (SS-14) and of its two analogues,
      octreotide and CH-275, on the activity of tyrosine kinases (TK) in two rodent
      tumors (rat pituitary tumor and murine colonic cancer) were studied in vitro. The
      activity of TK was measured in tissue homogenates using gamma[(32)P]ATP as the
      donor of the phosphoryl group and poly(Glu(80), Tyr(20)) as a substrate. It was
      found that native SS-14 inhibited TK activity in both investigated tumors.
      Octreotide, which acts preferentially via somatostatin receptor subtype 2
      (SSTR2), was very effective in inhibiting TK activity in the rat pituitary tumor,
      but it is a rather weak inhibitor of TK activity in murine colonic cancer. CH
      275, a selective ligand of the SSTR1 subtype of SS receptors, suppressed TK
      activity in the pituitary tumor but was ineffective in the colonic cancer. It is
      hypothesized that the effect of neuropeptide somatostatin (SS-14) on murine
      colonic cancer is exerted via the subtype of receptor which does not interact
      with CH-275 and has no or low affinity for octreotide (SSTR 4, 3 or 5?).

PMID- 10965063
TI  - Hypotension and ultrafiltration physiology in dialysis.

PMID- 10965062
TI  - Nonradioisotope assay of glucose uptake activity in rat skeletal muscle using
      enzymatic measurement of 2-deoxyglucose 6-phosphate in vitro and in vivo.
AB  - We investigated a nonradioisotope method for the evaluation of glucose uptake
      activity using enzymatic measurement of 2-deoxyglucose 6-phosphate (2DG6P)
      content in isolated rat soleus muscle in vitro and in vivo. The 2DG6P content in
      isolated rat soleus muscle after incubation with 2-deoxyglucose (2DG) was
      increased in a dose-dependent manner by insulin (ED(50) = 0.6 mU/ml), the maximum
      response being about 5 times that of the basal content in vitro. This increment
      was completely abolished by wortmannin (100 nM), with no effect on basal 2DG6P
      content. An insulin-mimetic compound, vanadium, also increased 2DG6P content in a
      dose-dependent manner. In isolated soleus muscle of Zucker fa/fa rats, well known
      as an insulin-resistant model, insulin did not increase 2DG6P content. The 2DG6P
      content in rat soleus muscle increased after 2DG (3 mmol/kg) injection in vivo,
      and conversely, the 2DG concentration in plasma was decreased in a dose-dependent
      manner by insulin (ED(50) = 0.11 U/kg). The maximum response of the accumulation
      of 2DG6P in soleus muscle was about 4 times that of the basal content. This
      method could be useful for evaluating glucose uptake (transport plus
      phosphorylation) activity in soleus muscle in vitro and in vivo without using
      radioactive materials.

PMID- 10965064
TI  - Advances in end-stage renal diseases 2000. Access monitoring methods.

PMID- 10965065
TI  - Effect of dialysate-side mass transfer resistance on small solute removal in
      hemodialysis.

PMID- 10965066
TI  - Limitations of membrane structure and dialyzer design on large solute removal in
      dialysis.

PMID- 10965067
TI  - New developments in hemodialyzers.

PMID- 10965068
TI  - Kt/V is the best dialysis dose parameter.

PMID- 10965070
TI  - Optimizing the dialysis dose with consideration of patient size.

PMID- 10965069
TI  - The normalized treatment ratio (Kt/V) is not the best dialysis dose parameter.

PMID- 10965072
TI  - Is there a role for protein restriction in the treatment of chronic renal
      failure?

PMID- 10965071
TI  - Should we treat patients with incremental dialysis prescriptions?

PMID- 10965074
TI  - Are observational studies 'just as effective' as randomized clinical trials?

PMID- 10965073
TI  - Another call for timely initiation of dialysis.

PMID- 10965075
TI  - Observational studies are just as effective as randomized clinical trials.

PMID- 10965076
TI  - The microinflammatory state of uremia.

PMID- 10965077
TI  - Interaction between nutrition and inflammation in end-stage renal disease.

PMID- 10965078
TI  - Interpretation of plasma protein measurements in end-stage renal disease.

PMID- 10965079
TI  - Evaluation of oxidant stress in dialysis patients.

PMID- 10965080
TI  - Staphylococcus aureus prophylaxis in dialysis patients.

PMID- 10965081
TI  - Infections due to antimicrobial-resistant pathogens in the dialysis unit.

PMID- 10965082
TI  - Advances in end-stage renal diseases 2000. Continuous-flow peritoneal dialysis.
      preliminary results.

PMID- 10965084
TI  - Transvenous pacing lead-induced thrombosis: a series of cases with a review of
      the literature.
AB  - Although transvenous pacing is a safe treatment modality for bradyarrhythmias,
      serious thrombotic and embolic complications are reported to occur in 0.6-3.5% of
      cases. We describe 5 cases of pacemaker-associated thrombosis, 3 with a superior
      vena cava syndrome (SVC), 1 with an axillary vein thrombosis and 1 with a
      thrombus attached to the pacing lead in the right atrium. All of the patients
      were initially treated with intravenous heparin which proved successful as the
      sole treatment in only the least severe case (axillary vein thrombosis). One of
      the patients with SVC obstruction was successfully treated with intravenous
      heparin followed by thrombolytic therapy. The remaining 3 cases (2 SVC syndromes
      and 1 right atrial thrombus) required surgical removal of thrombus and pacing
      leads. Both of the patients with evidence of infection were in the group for whom
      failure of medical therapy necessitated surgery.

PMID- 10965083
TI  - A randomized crossover evaluation of antianginal efficacy and safety of
      nitrolingual-spray and nitroglycerin tablet form in coronary artery disease
      patients.
AB  - Twenty-eight coronary artery disease patients with more than 50% stenosis in at
      least one major coronary artery completed this randomized crossover clinical
      trial for the comparison of efficacy and safety of Nitrolingual-Spray and
      nitroglycerin (NTG) tablets. Exercise time was lengthened to 399.1 s (spray) or
      408.5 s (tablets), compared to a baseline of 387.3 s. Ischemic burden decreased
      to about -4.0 mm with both forms, compared to -7.5 mm at baseline (ANOVA: p =
      0.003). The ischemic time improved to 137.2 s (spray) or 152.9 s (tablets),
      compared to 253.4 s at baseline (ANOVA: p = 0. 005). Patients taking tablets
      experienced more episodes of hypotension and/or headache compared to patients
      taking the spray. Nitrolingual-Spray is as effective and safe as NTG tablets for
      the treatment of symptomatic coronary heart disease.

PMID- 10965085
TI  - Impact of blood pressure control on prevalence of left ventricular hypertrophy in
      treated hypertensive patients.
AB  - AIM: The aim of the present study was to evaluate (1) the prevalence and patterns
      of left ventricular hypertrophy (LVH) and (2) the impact of blood pressure (BP)
      control, assessed by clinical and 24-hour ambulatory BP monitoring (ABPM)
      criteria on the persistence of LVH in a representative sample of treated patients
      attending our Hypertension Clinic. METHODS: One hundred consecutive essential
      hypertensives (61 m/39 f, age 56+/- 9 years) regularly followed up by the same
      medical team (average period 52 months, 12-156 months) were included in the study
      and underwent 24-hour ABPM and complete echocardiographic examination. RESULTS:
      Twenty-eight of the 100 patients were found to have LVH [left ventricular mass
      index (LVMI) >125 g/m(2) in men and >110 g/m(2) in women]; LVH was eccentric in
      20 patients and concentric in the remaining 8. LVMI did not correlate with
      clinical BP values but only with ABPM values (mean 24 h systolic r = 0.34, p
      <0.01; diastolic r = 0.37, p <0.01). The prevalence of LVH in patients controlled
      according to clinical BP criteria (n = 43, BP <140/90 mm Hg) was 19%, in patients
      controlled according to ABPM criteria (n = 30, BP during daytime <132/85 mm Hg)
      17%, and in those controlled with both criteria (n = 16) 6% (p <0. 01).
      CONCLUSIONS: The results of this study suggest that the eccentric type of LVH is
      the prevalent pattern in chronically treated patients. The persistence of LVH is
      significantly dependent on BP levels achieved during treatment; indeed the
      prevalence of LVH is very low in patients with an optimal BP control, whereas it
      is elevated (37%) in uncontrolled patients.

PMID- 10965086
TI  - Phenotypic variation of familial hypertrophic cardiomyopathy caused by the
      Phe(110)-->Ile mutation in cardiac troponin T.
AB  - Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of
      familial hypertrophic cardiomyopathy (HCM). A Japanese family of 14 individuals,
      including 6 with HCM, was subjected to genetic and clinical assessment. Five
      exons of the cTnT gene were sequenced in all family members. A heterozygous or
      homozygous T(340)-->A (Phe(110)-->Ile) mutation in exon 9 of the cTnT gene was
      detected in 11 subjects. Morphological and functional evaluation of the left and
      right ventricles by echocardiography revealed that 4 of 9 individuals
      heterozygous for the mutant allele exhibited HCM with moderate cardiac
      hypertrophy. Cardiac hypertrophy and other clinical features in the 2 subjects
      homozygous for the mutation were more severe than were those in heterozygous
      individuals with HCM. Thus, the clinical features of HCM due to the Phe(110)-
      >Ile mutation in the cTnT gene appear to be modified by a gene dosage effect.

PMID- 10965087
TI  - Correlation of predischarge electrocardiographic patterns with left ventricular
      function in patients with anterior wall myocardial infarction.
AB  - The aim of this prospective study was to assess the correlation between different
      predischarge electrocardiographic patterns and left ventricular function,
      evaluated by physical examination and echocardiography, in patients with first Q
      wave anterior acute myocardial infarction. A positive correlation was found
      between the electrocardiographic pattern and wall motion score assessed by
      echocardiography, reflecting a gradual worsening in left ventricular function
      among the different patterns. Patients with an isoelectric ST segment and
      negative T waves had a 73% decrease in the risk of clinical heart failure
      compared to those who continued to have ST elevation. Thus, a predischarge
      electrocardiogram can be used as a simple, noninvasive method for the risk
      stratification of patients with acute myocardial infarction.

PMID- 10965088
TI  - Serial changes in serum VEGF and HGF in patients with acute myocardial
      infarction.
AB  - The time course of vascular endothelial growth factor (VEGF) and hepatocyte
      growth factor (HGF) release in patients with acute myocardial infarction (AMI) is
      unknown. Blood samples were obtained at the time of admission and 3, 7, 14 and 21
      days later in 32 patients with AMI and 30 control patients. Serum VEGF and HGF,
      as well as C-reactive protein (CRP) and amyloid A protein (SAA), were determined.
      Both serum VEGF and HGF levels on admission in patients with AMI were higher than
      control values and peaked on day 7. VEGF levels in patients with preinfarction
      angina were higher than in patients with no preinfarction angina, whereas the HGF
      level did not differ. Both CRP and SAA levels peaked on day 3, and the CRP level
      on day 3 correlate with both VEGF and HGF levels on day 7. We hypothesized that
      the serum VEGF level is associated with preinfarction ischemia and the increase
      in VEGF and HGF on day 7 of AMI may represent a response to acute inflammation.

PMID- 10965089
TI  - Hemodynamic and hormonal effects of the angiotensin II antagonist, candesartan
      cilexetil, in patients with congestive heart failure.
AB  - Candesartan cilexetil is a newly synthesized, specific angiotensin II type 1
      receptor antagonist. Candesartan cilexetil is a prodrug, and is converted to its
      active form, candesartan, by the enzyme esterase at the time of intestinal
      absorption. We conducted a single-dose study to evaluate the effect of
      candesartan cilexetil on cardiac hemodynamics and hormone response in 13 patients
      with congestive heart failure. Mean blood pressure did not show any significant
      change in the patients receiving either 2 or 8 mg. Pulmonary capillary wedge
      pressure was reduced by 34.9% in the patients given 8 mg of candesartan
      cilexetil. The cardiac index did not show any significant changes. Total
      peripheral vascular resistance was reduced in the patients receiving 2 or 8 mg
      from 1 h after administration, and the tendency to decrease continued until 8 h
      after administration. Plasma atrial natriuretic peptide levels were reduced by
      15.5% 2 h after dosing with 8 mg of candesartan cilexetil. Plasma brain
      natriuretic peptide levels decreased slightly after dosing with candesartan
      cilexetil. Administration of candesartan cilexetil reduces cardiac preload and
      afterload and is expected to be useful for the treatment of congestive heart
      failure.

PMID- 10965090
TI  - Prognostic value of ischemia monitoring with on-line vectorcardiography in
      patients with unstable coronary artery disease.
AB  - AIM: The aim of this study was to determine whether on-line vectorcardiography
      (VCG) gives independent prognostic information, regarding death, myocardial
      infarction (MI), and revascularization in patients with unstable coronary artery
      disease, i.e. unstable angina or non-Q-wave MI. METHODS AND RESULTS: One hundred
      and fifty patients (mean age 69 +/- 10), participating in a randomized study of
      low-molecular-weight heparin in unstable coronary artery disease, were studied
      with on-line VCG recordings for 24 h. During a 5-6-month follow-up, 11 patients
      died, 14 suffered a nonfatal MI and 31 were revascularized. Univariate predictors
      of death were diabetes mellitus (p < 0.01), maximum ST vector magnitude (ST-VM; p
      < 0.001), maximum ST change vector magnitude (STC-VM; p < 0.001), number of ST-VM
      (p < 0.01) and STC-VM episodes (p < 0.001). In multivariate analysis, the number
      of STC-VM episodes (p < 0.01) and diabetes mellitus (p < 0.02) each gave
      independent prognostic information regarding death. When all cardiovascular
      events were combined, the inability to perform an exercise test (p < 0.05),
      maximum value of ST-VM (p < 0.01) and STC-VM (p < 0.001), the number of episodes
      of STC-VM (p < 0.001) and ST-VM (p < 0.001) all gave prognostic information. In
      multivariate analysis, the inability to perform an exercise test and the number
      of STC-VM episodes were independent predictors. CONCLUSION: VCG monitoring during
      the first 24 h of hospitalization for unstable coronary artery disease gives
      independent prognostic information.

PMID- 10965092
TI  - Evolution of left ventricular involvement in arrhythmogenic right ventricular
      cardiomyopathy.
AB  - Left ventricular (LV) involvement in arrhythmogenic right ventricular
      cardiomyopathy (ARVC) is fairly well known, but the evolution of LV involvement
      during long-term follow-up has not been well documented. We describe such
      evolution in a patient followed for 9 years. Evolution was confirmed by a
      progressive perfusion defect of the LV wall in myocardial scintigrams and by the
      development of LV asynergy with ventricular aneurysm formation in left
      ventriculograms. As the right ventricle progressively enlarged, we concluded that
      ARVC is a diffuse and progressive myocardial disease that affects both
      ventricles.

PMID- 10965091
TI  - Circulating interleukin-6 and interleukin-6 receptors in patients with acute and
      recent myocardial infarction.
AB  - Interleukin-6 (IL-6), a proinflammatory cytokine, plays a key role in the
      pathogenesis of coronary artery disease (CAD). We investigated circulating IL-6
      and its receptors in patients with CAD. We evaluated 39 Japanese patients with
      CAD (30 males and 9 females aged 36-79 years), measuring their plasma levels of
      IL-6 and IL-6 receptors alpha and beta (IL-6R alpha, IL-6R beta). Circulating
      levels of IL-6, IL-6R alpha and IL-6R beta were measured by an enzyme-linked
      immunosorbent assay. Blood was sampled immediately after admission and again
      after 1, 2, 3, 6 and 9 h, then every 12 h for 5 days. Atrial natriuretic peptide
      (ANP) and B-type natriuretic peptide (BNP) were measured on day 3 after symptom
      onset. Plasma levels of IL-6 and IL-6Rs were significantly increased in 28
      patients with acute myocardial infarction (AMI) compared with 15 normal controls.
      However, neither IL-6 nor IL-6Rs showed an increase in 6 patients with angina
      pectoris. We observed two peaks for circulating IL-6 in AMI, the first of which
      showed a significant correlation with ANP as well as BNP. These results may help
      to explain why the amount of IL-6 produced is closely related to the severity of
      myocardial dysfunction in patients with CAD.

PMID- 10965093
TI  - Segmental wall motion abnormalities in an individual with idiopathic pulmonary
      hemosiderosis.
AB  - Idiopathic pulmonary hemosiderosis (IPH) is a rare condition characterized by
      diffuse pulmonary hemorrhage of unknown etiology. Cardiac involvement in the form
      of myocarditis and right ventricular hypertrophy have been reported to occur in
      association with IPH, although findings on echocardiography have not been
      described. Herein is presented a case of an adult with IPH and echocardiographic
      abnormalities.

PMID- 10965094
TI  - Time-kill studies of antimicrobial combinations including cefotaxime,
      ceftriaxone, vancomycin and meropenem against cephalosporin-resistant
      Streptococcus pneumoniae.
AB  - BACKGROUND: Resistance of Streptococcus pneumoniae to penicillin is now
      widespread and rapidly increasing all over the world. This has led to the
      critical need for alternative antimicrobial therapy. METHODS: To assess the
      activities of antimicrobial combinations, including cefotaxime, ceftriaxone,
      vancomycin and meropenem, time-kill studies were conducted against five strains
      of penicillin- and cephalosporin-resistant S. pneumoniae at clinically achievable
      antimicrobial concentrations in cerebrospinal fluid. RESULTS: Combinations of an
      extended-spectrum cephalosporin with vancomycin were not synergistic. Meropenem
      had a comparable bactericidal activity to those combinations, and its killing
      activity was not affected by the addition of cefotaxime, ceftriaxone or
      vancomycin. CONCLUSIONS: It is suggested that meropenem could be an effective
      alternative for the treatment of penicillin- and cephalosporin-resistant
      pneumococcal meningitis. However, more clinical data are required before it can
      be recommended as an effective antimicrobial agent for such cases.

PMID- 10965095
TI  - Comparative in vitro activity of older and newer fluoroquinolones against
      respiratory tract pathogens.
AB  - The aim of this study was to evaluate the antibacterial activity of older
      (ciprofloxacin and ofloxacin) and newer (moxifloxacin, grepafloxacin,
      sparfloxacin and levofloxacin) fluoroquinolones. Minimal inhibitory
      concentrations (MICs) were determined, according to the NCCLS guidelines, against
      the following respiratory tract pathogens: penicillin-susceptible and -resistant
      Streptococcus pneumoniae, beta-lactamase-positive and beta-lactamase-negative
      Haemophilus influenzae and beta-lactamase-positive Moraxella catarrhalis. In
      addition, we evaluated the minimal bactericidal concentrations of the same
      antibiotics against all the pneumococci and the haemophili. Finally, the activity
      of ciprofloxacin, ofloxacin, sparfloxacin and moxifloxacin against 15 pneumococci
      were investigated by time-kill analysis. All fluoroquinolones tested exhibited a
      similar, good activity against H. influenzae and M. catarrhalis. Against S.
      pneumoniae, irrespective of penicillin susceptibility, moxifloxacin,
      grepafloxacin, sparfloxacin and levofloxacin exhibited excellent activity, better
      than ciprofloxacin and ofloxacin. Time-kill analysis showed that 99.9% killing of
      all strains was obtained after 24 h with moxifloxacin at 2 x MIC, whereas other
      antimicrobials obtained similar results at 4 x MIC. Moxifloxacin is characterized
      by an improved activity against respiratory pathogens, including penicillin
      resistant and -susceptible S. pneumoniae. Its activity is not influenced by beta
      lactamase production. These results suggest that moxifloxacin represents a
      promising alternative for treatment of respiratory tract infections.

PMID- 10965096
TI  - Antibiotic susceptibility of Serratia marcescens and Serratia liquefaciens.
AB  - BACKGROUND: Over a period of 20 years, a total of 1,603 Serratia isolates were
      recovered from clinical specimens and examined for susceptibility to 29
      antimicrobial drugs using the Bauer-Kirby agar disk diffusion test. Serratia
      marcescens was recovered most frequently (n = 1,409), followed by S. liquefaciens
      (n = 172); other Serratia species were scarce. During the 2-decade observation
      period there occurred 35 putative episodes/clusters of nosocomial cross-infection
      and 1 pseudo-outbreak due to S. marcescens, but none due to S. liquefaciens.
      METHODS: The antimicrobial susceptibility data for S. marcescens and S.
      liquefaciens were subdivided into two observation periods: I = 1980-1993, and II
      = 1993-1999. The crude data (series A) obtained for S. marcescens were corrected
      in two ways: by the omission of repetitive patient isolates (series B) and the
      additional removal of outbreak isolates except for index case isolates (series
      C). RESULTS AND CONCLUSIONS: Comparison of data obtained in series IC and IIC
      disclosed an increase in the susceptibility of S. marcescens to ampicillin +
      sulbactam, cefotaxime, chloramphenicol, doxycycline, fosfomycin, gentamicin,
      piperacillin, piperacillin + tazobactam, timentin and tobramycin during
      observation period II. Conversely, there was a decrease in susceptibility to
      ciprofloxacin, nalidixic acid and trovafloxacin, and slightly diminished
      susceptibility to norfloxacin and ofloxacin during observation period II as
      compared with the previous period. The crude data obtained for S. liquefaciens
      required no correction, as there were only a few repeat isolates. There was an
      increase in susceptibility to ampicillin, ampicillin + sulbactam, cefuroxime,
      doxycycline, fosfomycin, nitrofurantoin and polymyxin B (clear inhibition zones).
      However, there was an inexplicable decrease in susceptibility to piperacillin +
      tazobactam. Cocarde growth around polymyxin B disks was noted with 55.8% of the
      S. marcescens isolates as compared with 6.8% of the S. liquefaciens isolates.
      Slime around fluoroquinolone inhibition zones was produced by 83.4% of the S.
      marcescens isolates. Slime production around carbapenem inhibition zones was
      noted with 52% of the S. liquefaciens isolates, but with only a single isolate of
      S. marcescens.

PMID- 10965097
TI  - Potential salvage therapy for accidental intrathecal vincristine administration:
      a preliminary experimental study.
AB  - BACKGROUND: Accidental intrathecal vincristine (VCR) administration results in
      severe neurotoxicity, usually fatal in outcome. No specific therapy for
      initrathecal VCR toxicity has been reported so far. In our recent report,
      complete in vitro degradation of VCR by hypochlorous acid (HOCl) was
      demonstrated. METHODS: In this comparative study, we examined the in vivo
      effectiveness of HOCl in the cerebrospinal fluid of 24 New Zealand rabbits
      following intracisternal VCR administration. RESULTS: There were no significant
      clinical or histopathologic abnormalities in the control and HOCl groups;
      however, multiple necrotic foci on histopathological examination of brain
      sections in the VCR group were determined. There were significantly lower numbers
      of necrotic foci in brain sections of rabbits which received HOCl administration
      than those without therapy. CONCLUSION: Our results indicate that HOCl may reduce
      VCR neurotoxicity.

PMID- 10965098
TI  - Taxol resistance.
AB  - BACKGROUND: Taxol has gained considerable attention in cancer therapy in recent
      years and is successfully used in treating a variety of tumors, including those
      of the breast, ovary and lung. Despite its preclinical and clinical success, the
      ability of tumors to develop an acquired resistance to drugs used for treatment
      remains a major obstacle to cancer cure. A better understanding of the various
      mechanisms of Taxol resistance may have important implications for strategies
      designed for cancer treatment. METHOD: This review summarizes the information
      available to date concerning the effects of Taxol and the development of drug
      resistance, focusing particularly on alterations in microtubules. RESULTS AND
      DISCUSSION: Acquired resistance to Taxol is a function of multiple adaptations.
      Although the cellular transport of Taxol appears to be an important mechanism of
      resistance to Taxol, altered transcription and posttranslational modification of
      microtubular changes may be involved in the mechanism of drug resistance.

PMID- 10965099
TI  - Prediction of flucytosine-induced thrombocytopenia using creatinine clearance.
AB  - AIMS: To evaluate and investigate the efficacy and accuracy of an earlier derived
      relationship between thrombocyte nadir and mean creatinine clearance in order to
      make it possible to predict flucytosine (5-FC)-related thrombocytopenia. METHODS:
      The earlier derived relationship between thrombocyte nadir and mean creatinine
      clearance is validated using a patient population of 35 intensive care unit (ICU)
      patients. Patients have to meet the inclusion criteria as defined in the initial
      study (i.e., developing thrombocytopenia during 5-FC treatment or remaining
      within the normal thrombocyte range; individual pharmacokinetic parameters within
      certain limits; a minimum of three measured 5-FC serum levels). RESULTS: Of a
      total of 35 patients, 11 are eligible since they meet the inclusion criteria as
      defined in the initial study. A significant relationship between the observed and
      predicted thrombocyte nadir values can be derived: Y(pred) = 0.608.X(obs) + 24.
      330 (r = 0.615; t(obs) = 2.337; t at p < 0.05 and 9 degrees of freedom = 2.262).
      The predicted value of the thrombocyte nadir corresponds with a mean prediction
      error (bias) of -18.3 (95% CI -45.9; 9.4) and a root mean squared prediction
      error (precision) of 48.3 (95% CI 23.9-63.9). CONCLUSION: The earlier derived
      relationship between thrombocyte nadir and mean creatinine clearance is accurate
      and precise. However, due to the strict inclusion criteria used to derive and
      validate this relationship, it cannot be applied to all 5-FC-treated patients.

PMID- 10965100
TI  - In vitro comparative dynamics of modified-release clarithromycin and of
      azithromycin.
AB  - Antibacterial kinetics of modified-release clarithromycin (CLA) and azithromycin
      (AZI) against respiratory tract pathogens were compared in relation to their
      pharmacokinetic profile. The study was carried out in three strains of
      Streptococcus pneumoniae, group A beta-hemolytic Streptococcus pyogenes,
      Moraxella catarrhalis and Haemophilus influenzae, respectively, exposed to
      concentration gradients of CLA and AZI simulating human serum pharmacokinetics
      after administration of 500 mg p.o. in a single dose. Bactericidal kinetics were
      assessed by counting the number of survivors before each change in concentration
      over a period of 36 h. The minimal inhibitory concentrations (MICs) of CLA and
      AZI were evaluated at time 0 and after 36 h of exposure to antibiotics in the
      surviving organisms. The results showed that CLA and AZI, in the experimental
      conditions adopted, had different antibacterial kinetics. Moreover, the addition
      of the 14-OH metabolite of CLA at the same concentrations reached in human serum
      exerted a bactericidal effect against two strains of H. influenzae resistant to
      CLA and AZI. An increase in MICs was observed against S. pyogenes and H.
      influenzae, with higher values for AZI.

PMID- 10965101
TI  - Perioperative infection prophylaxis and risk factor impact in colon surgery.
AB  - BACKGROUND: A prospective observational study was undertaken in 2, 481 patients
      undergoing elective colon resection in 114 German centers to identify optimal
      drug and dosing modalities and risk factors for postoperative infection. METHODS:
      Patients were pair matched using six risk factors and divided into 672 pairs
      (ceftriaxone vs. other cephalosporins, group A) and 400 pairs (ceftriaxone vs.
      penicillins, group B). End points were local and systemic postoperative infection
      and cost effectiveness. RESULTS: Local infection rates were 6.0 versus 6.5%
      (group A) and 4.0 versus 10.5% (group B); systemic infection rates in groups A
      and B were 4.9 versus 6.3% and 3.3 versus 10.5%, respectively. Ceftriaxone was
      more effective than penicillins overall (6.8 vs. 17.8%, p < 0.001). Length of
      postoperative hospital stay was 16.2 versus 16.9 days (group A) and 15.8 versus
      17.6 days (group B). Of the six risk factors, age and concomitant disease were
      significant for systemic infection, and blood loss, rectum resection and
      immunosuppressive therapy were significant for local infection. Penicillin was a
      risk factor compared to ceftriaxone (p < 0.0001). Ceftriaxone saved 160.7 EUR
      versus other cephalosporins and 416.2 EUR versus penicillins. CONCLUSION:
      Clinical and microbiological efficacy are responsible for the cost effectiveness
      of ceftriaxone for perioperative prophylaxis in colorectal surgery.

PMID- 10965102
TI  - Ondansentron and dexamethasone treatment with different dosing schedules (24
      versus 32 mg) in patients with non-small-cell lung cancer under cisplatin-based
      chemotherapy: a randomized study.
AB  - The purpose of this study was to determine whether ondansentron given to patients
      with non-small-cell lung cancer (NSCLC) undergoing cisplatin-based chemotherapy,
      has better antiemetic activity administered every 6 or 8 h in controlling
      cisplatin-induced emesis. All patients had previously received 3 cycles of
      cisplatin-based chemotherapy at a dose of 100 mg/m(2). Ondansentron was given
      according to two schedules in group A (50 patients) at a dose of 8 mg in 100 ml
      normal saline over 10 min i.v. infusion, together with dexamethasone 8 mg before
      the infusion of cisplatin, continued with both drugs at the same dose and
      administration after 8 and 16 h; in group B (50 patients) both drugs were
      administered before the infusion of cisplatin, continued after 6, 12 and 18 h.
      During the next 3 days, patients continued with tablets of dexamethasone 4 mg and
      ondansentron 8 mg, group A every 8 h, and group B every 6 h. The only difference
      in terms of antiemetic response that was noticed between the two groups was the
      number of patients experiencing nausea which was found increased in group A (n =
      32) in comparison to group B (n = 25) (p < 0.022). No difference was noticed in
      the number of vomiting episodes and retches or emesis control, during the 3-day
      evaluation period after cisplatin infusion or in side effects. In conclusion, the
      total dose of 24 mg ondansentron during the acute phase of emesis is as effective
      as the total dose of 32 mg.

PMID- 10965104
TI  - Localization of the human anterior gradient-2 gene (AGR2) to chromosome band
      7p21.3 by radiation hybrid mapping and fluorescencein situ hybridisation.

PMID- 10965105
TI  - Assignment of the calcium-binding mitochondrial carrier Aralar1 gene (SLC25A12)
      to human chromosome band 2q31 by in situ hybridization.

PMID- 10965103
TI  - Safety and efficacy of cefpirome in comparison with ceftazidime in Chinese
      patients with sepsis due to bacterial infections.
AB  - BACKGROUND: The safety and efficacy of cefpirome (CPM), a fourth-generation
      cephalosporin, has not yet been studied in an Asian population. METHODS: Sixty
      nine adult Chinese patients with sepsis due to bacterial infections were enrolled
      in the study and randomly assigned to receive CPM (2 g i.v. every 12 h) or
      ceftazidime (2 g i.v. every 8 h). RESULTS: Both groups were comparable in terms
      of demographic, clinical and microbiological features. The causative pathogen was
      Escherichia coli or Klebsiella pneumoniae in the majority of microbiologically
      documented cases. The rates of clinical response (94 vs. 94%) and bacteriological
      response (65 vs. 68%) were similar in both groups. Similar adverse events,
      including rashes, gastrointestinal upset and asymptomatic elevation of hepatic
      enzymes, occurred in a minority of patients in both groups. All events were self
      limited after discontinuation of the drugs. CONCLUSION: CPM is as safe and
      effective as ceftazidime in the treatment of sepsis due to bacterial infections
      in Chinese patients.

PMID- 10965107
TI  - Assignment of brain acid-soluble protein 1 (BASP1) to human chromosome 5p15.1-
      >p14, differential expression in human cancer cell lines as a result of
      alterations in gene dosage.

PMID- 10965106
TI  - Assignment of the mitochondrial translation elongation factor Ts gene (TSFM) to
      human chromosome 12 bands q13-->q14 by in situ hybridization and with somatic
      cell hybrids.

PMID- 10965109
TI  - Isolation and assignment of the UDP-glucose pyrophosphorylase gene (UGP2) to
      porcine chromosome 3q21-->q22 by FISH and by analysis of somatic cell and
      radiation hybrid panels.

PMID- 10965108
TI  - Molecular cloning, chromosomal localization, and expression of the murine SALL1
      ortholog Sall1.
AB  - SALL1 has been identified as one of now three human homologs of the region
      specific homeotic gene spalt (sal) of Drosophila, which encodes a zinc finger
      protein of characteristic structure. Mutations of SALL1 on chromosome 16q12.1
      cause Townes-Brocks syndrome (TBS, OMIM no. 107480). In order to facilitate
      functional studies of this gene in a model organism, we searched for the murine
      homolog of SALL1. Here we report the genomic cloning, chromosome mapping, and
      partial expression analysis of the gene Sall1. Sequence comparison, Northern blot
      hybridization as well as the conserved chromosome location on the homologous
      mouse chromosome indicate that we have indeed isolated the murine homolog of
      SALL1.

PMID- 10965110
TI  - Assignment of the human zinc finger gene, ZNF288, to chromosome 3 band q13.2 by
      radiation hybrid mapping and fluorescence in situ hybridisation.

PMID- 10965111
TI  - Assignment of the ectodermal-neural cortex 1 gene (Enc1) to mouse chromosome band
      13D1 by fluorescence in situ hybridization.

PMID- 10965112
TI  - Assignment of CDK5R2 coding for the cyclin-dependent kinase 5, regulatory subunit
      2 (NCK5AI protein) to human chromosome band 2q35 by fluorescent in situ
      hybridization.

PMID- 10965113
TI  - Assignment of the troponin C2 fast gene (TNNC2) to porcine chromosome bands
      17q2.1-->q2.2 by in situ hybridization.

PMID- 10965114
TI  - Assignment of ankyrin repeat, family A (RFXANK-like) 2 (ANKRA2) to human
      chromosome 5q12-->q13 by radiation hybrid mapping and somatic cell hybrid PCR.

PMID- 10965115
TI  - Assignment of interleukin-1 receptor, type I (IL1R1) to bovine chromosome band
      11q12 by in situ hybridization.

PMID- 10965116
TI  - An anchored YAC-STS framework for the rat genome.
AB  - We report here the first YAC-STS framework for the rat genome. A total of 417
      anchor microsatellite markers were used to screen a 10-fold redundant YAC
      library. One or more unambiguous YACs were identified for 372 markers. Assuming
      the genetic length of the rat genome to be 2,000 cM (Bihoreau et al. 1997b), the
      YAC-STS framework will provide, on average, one informative YAC clone every 5.4
      cM. A total of 111 anchor markers used in this study were derived from known gene
      regions. We also demonstrated one of the important and immediate uses of this YAC
      STS framework, which is to establish a correlation between the genetic and
      cytogenetic maps in the rat through FISH analysis.

PMID- 10965117
TI  - Comparative FISH mapping of bovid X chromosomes reveals homologies and
      divergences between the subfamilies bovinae and caprinae.
AB  - Comparative FISH mapping of river buffalo (Bubalus bubalis, BBU), sheep (Ovis
      aries, OAR), and cattle (Bos taurus, BTA) X chromosomes revealed homologies and
      divergences between the X chromosomes in the subfamilies Bovinae and Caprinae.
      Twenty-four and 17 loci were assigned for the first time to BBU X and OAR X,
      respectively, noticeably extending the physical map in these two species.
      Seventeen loci (four of which for the first time) were also FISH mapped to BTA X
      and used for comparative mapping studies on the three species, which show three
      morphologically different X chromosomes: an acrocentric (BBU X), an acrocentric
      with distinct short arms (OAR X), and a submetacentric (BTA X). The same order of
      loci were found on BTA X and BBU X, suggesting that a centromere transposition,
      with loss (cattle) or acquisition (river buffalo) of constitutive
      heterochromatin, differentiated the X chromosomes of these two bovids. Comparison
      of bovine (cattle and river buffalo) and caprine (sheep) X chromosomes revealed
      at least five common chromosome segments, suggesting that multiple
      transpositions, with retention or loss of constitutive heterochromatin, had
      occurred during their karyotypic evolution.

PMID- 10965118
TI  - A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's
      amyloid precursor protein beta-secretase.
AB  - Down syndrome individuals develop abnormalities of most organs, including all the
      pathological and neurochemical features of Alzheimer's disease, by the early age
      of 30 yr. Here, we report the isolation and characterization of BACE2, a gene
      mapping on human chromosome 21q22.3, which is highly similar to a transmembrane
      aspartyl protease, BACE (for beta-site APP-cleaving enzyme), which is able to
      catalyze the beta-secretase cleavage of Alzheimer's amyloid precursor protein
      (APP). BACE2 is expressed in a wide variety of organs and tissues, with several
      transcripts due to alternative splicing and the use of two polyadenylation
      signals. The BACE2 gene product is a 518 amino acid protein with the signature of
      an aspartic protease, a 20-residue signal peptide, and two putative N
      glycosylation sites. In addition, and similarly to BACE, BACE2 differs from the
      other members of the human aspartic protease family in the number and
      distribution of putative disulfide bonds and in the presence of an extended C
      terminal region which contains a predicted transmembrane segment. BACE2 could be
      involved in the Alzheimer-like neuropathology of Down syndrome, as well as in
      Alzheimer's disease linked to chromosome 21 but not showing mutations in APP.

PMID- 10965119
TI  - Characterization and genomic localization of the mouse Extl2 gene.
AB  - Human EXTL2 is an alpha1,4-N-acetylhexosaminyltransferase involved in the
      biosynthesis of heparin/heparan sulfate. We have cloned and characterized the
      mouse homolog of this gene. Mouse Extl2 encodes a 330 amino acid protein that is
      87% identical to its human counterpart. Expression analysis showed that Extl2 is
      ubiquitously expressed in adult mouse tissues and that the Extl2 transcript is
      already present in early stages of embryonic development. Determination of the
      genomic structure revealed that the Extl2 gene spans five exons within a 10-kb
      region and that the genomic organization between mouse and man is well preserved,
      with conservation of the number and position of all five exons. By radiation
      hybrid analysis, Extl2 was mapped to mouse chromosome 3, in a region homologous
      to the human EXTL2 region on chromosome 1.

PMID- 10965120
TI  - Predivision of chromosomes in human oocytes: a reappraisal of cytogenetic
      nomenclature.

PMID- 10965122
TI  - Genomic organization and assignment of VAMP2 to 17p12 by FISH.
AB  - We describe the complete sequence, genomic organization, and FISH chromosome
      mapping of the human VAMP2. We identified a 7-kb clone, pISSHG2b3A, containing
      the entire structure of VAMP2. Previous studies performed by others identified a
      5-kb clone, pVPC5-2, containing the incomplete VAMP2. The pVPC5-2 clone was
      partially sequenced and mapped to the broad region 17pter-->p12 by somatic cell
      hybridization. Our clone overlaps the pVPC5-2 clone and extends approximately 2
      kb at the 3' end. In this study, we mapped this gene more precisely on 17p12 by
      FISH and we found a new polymorphic microsatellite, (GT)(7)CC(GT)(5), in exon V.
      This microsatellite, revealing three alleles with frequencies of 0.778, 0.139,
      and 0.083, might be useful for future linkage studies. Finally, we localized
      three previously known markers, stSG12859, TIGR-A002F11, and WIAF-1699 (alias
      stSG4044), in the 3' untranslated region of the gene.

PMID- 10965121
TI  - Direct visualization of the genomic distribution and organization of two cervid
      centromeric satellite DNA families.
AB  - Several repetitive DNA fragments were generated from PCR amplifications of
      caribou DNA using primer sequences derived from the white-tailed deer satellite
      II DNA clone OvDII. Two fragments, designated Rt-0.5 and Rt-0.7, were sequenced
      and found to have 96% sequence similarity. These caribou clones also had 85%
      sequence similarity with OvDII. Multiple-colored fluorescence in situ
      hybridization (FISH) studies with satellite I and satellite II DNA probes to
      caribou metaphase chromosomes and extended chromatin fibers provided direct
      visualization of the genomic organization of these two satellite DNA families,
      with the following findings: (1) Cervid satellite I DNA is confined to the
      centromeric regions of the acrocentric autosomes, whereas satellite II DNA is
      found at the centromeric regions of all chromosomes except for the Y. (2) For
      most acrocentric chromosomes, the satellite I signal appeared to be medially
      located at the primary constriction, in contrast to that of satellite II, which
      appeared to be oriented toward the lateral sides as two separate fluorescent
      dots. (3) The satellite II clone Rt-0.7 appeared to be enriched in the
      centromeric region of the caribou X chromosome, a pair of biarmed autosomes, and
      a number of other acrocentric autosomes. (4) Fiber-FISH demonstrated that the
      satellite I and satellite II arrays were juxtaposed. On highly extended chromatin
      fibers, the total length of the hybridization signals for the two satellite DNA
      arrays often reached 300-400 microm. The length of a given satellite II array
      usually reached 200 microm, corresponding to 2 x 10(3) kb of DNA in a given
      centromere.

PMID- 10965123
TI  - cDNA cloning of putative rat acetyl-CoA transporter and its expression pattern in
      brain.
AB  - Rat acetyl-CoA transporter gene (Acatn) encodes a hydrophobic multi-transmembrane
      protein involved in the O-acetylation of gangliosides. O-acetylated gangliosides
      have been found to play important roles in the embryonic development of the
      nervous system. We have isolated rat Acatn cDNA by PCR cloning. The amino acid
      sequence of rat Acatn exhibited 92% and 96% homology with human and mouse
      sequences, respectively. The mRNA was expressed in brain at all developmental
      stages. Acatn expression was higher in embryonic and postnatal rats than in adult
      rats. Cellular localization of Acatn mRNA in adult rat brain was also analyzed by
      in situ hybridization. Acatn mRNA expression was detected in the neuronal cells
      of cerebellum, hippocampus, hypothalamus, cortex, olfactory bulb, and dorsal and
      ventral anterior olfactory nucleus in adult rat brain.

PMID- 10965125
TI  - Assignment of the RNA-specific adenosine deaminase gene (Adar) to mouse
      chromosome 3F2 by in situ hybridization.

PMID- 10965124
TI  - Comparative mapping of seven genes in mouse, rat and Chinese hamster chromosomes
      by fluorescence in situ hybridization.
AB  - By fluorescence in situ hybridization (FISH) using mouse probes, we assigned
      homologues for cathepsin E (Ctse), protocadherin 10 (Pcdh10, alias OL
      protocadherin, Ol-pc), protocadherin 13 (Pcdh13, alias protocadherin 2c, Pcdh2c),
      neuroglycan C (Cspg5) and myosin X (Myo10) genes to rat chromosomes (RNO) 13q13,
      2q24-->q25, 18p12-->p11, 8q32.1 and 2q22.1-->q22.3, respectively. Similarly,
      homologues for mouse Ctse, Pcdh13, Cspg5 and Myo10 genes and homologues for rat
      Smad2 (Madh2) and Smad4 (Madh4) genes were assigned to Chinese hamster
      chromosomes (CGR) 5q28, 2q17, 4q26, 2p29-->p27, 2q112-->q113 and 2q112-->q113,
      respectively. The chromosome assignments of homologues of Ctse and Cspg5
      reinforced well-known homologous relationships among mouse chromosome (MMU) 1,
      RNO 13 and CGR 5q, and among MMU 9, RNO 8 and CGR 4q, respectively. The
      chromosome locations of homologues for Madh2, Madh4 and Pcdh13 genes suggested
      that inversion events were involved in chromosomal rearrangements in the
      differentiation of MMU 18 and RNO 18, whereas most of MMU 18 is conserved as a
      continuous segment in CGR 2q. Furthermore, the mapping result of Myo10 and
      homologues suggested an orthologous segment of MMU 15, RNO 2 and CGR 2.

PMID- 10965126
TI  - Assignment of the centrosomal protein 110 gene (Cep110) to mouse chromosome bands
      2B-C1 by in situ hybridization.

PMID- 10965127
TI  - Assignment of B-cell lymphoma 6, member B (zinc finger protein) gene (BCL6B) to
      human chromosome 17p13.1 by in situ hybridization.

PMID- 10965128
TI  - The genomic structure, chromosome location, and analysis of the human DKK1 head
      inducer gene as a candidate for holoprosencephaly.
AB  - Holoprosencephaly (HPE) is the most common developmental defect of the brain and
      face in humans. Here we report the analysis of the human ortholog of dkk-1 as a
      candidate gene for HPE. We determined the genomic structure of the human gene
      DKK1 and mapped it to chromosome 10q11.2. Functional analysis of four missense
      mutations identified in HPE patients revealed preserved activity in head
      induction assays in frogs suggesting a limited role for this gene in HPE
      pathogenesis.

PMID- 10965129
TI  - Structure and chromosome location of Smtn, the mouse smoothelin gene.
AB  - Smoothelins are cytoskeleton-associated proteins that are found in contractile
      smooth muscle. Two isoforms have been identified: smoothelin-A, expressed in
      visceral tissues and smoothelin-B, found in vascular tissues. The mouse
      smoothelin gene (Smtn) was isolated and characterized. It was assigned to
      chromosome 11 band A2-A3 by fluorescence in situ hybridization. The gene consists
      of 20 exons and spans 23 kb. Its structure is conserved between mouse and human.
      The proximal promoter of both smoothelin-A and smoothelin-B contains several
      transcription factor-binding sites but lacks a consensus TATA box.

PMID- 10965130
TI  - The p53-inducible gene EI24/PIG8 localizes to human chromosome 11q23 and the
      proximal region of mouse chromosome 9.
AB  - Activation of the p53 tumor suppressor leads to either a cell cycle arrest or to
      apoptosis and the factors that influence these responses are poorly understood.
      It is clear, however, that p53 regulates these processes by inducing a series of
      downstream target genes. One recently identified p53-target gene, EI24 (alias
      PIG8), induces apoptosis when ectopically expressed. To better understand the
      biological properties of EI24 and its potential relevance to disease, in
      particular cancer, we determined the chromosomal location and pattern of gene
      expression of EI24. EI24 is widely expressed in adult tissues and throughout
      mouse embryogenesis. The genomic locus of EI24 was mapped to the proximal region
      of mouse chromosome 9 and human chromosome 11q23-->q24, a region frequently
      altered in human cancers. These results suggest that EI24 may play an important
      role in the p53 tumor suppressor pathway.

PMID- 10965131
TI  - Assignment of PDZ domain-containing protein GIPC gene (C19orf3) to human
      chromosome band 19p13.1 by in situ hybridization and radiation hybrid mapping.

PMID- 10965132
TI  - Assignment of the rat calcineurin inhibitor gene (Cain) to rat chromosome band
      20p12 by fluorescence in situ hybridization.

PMID- 10965133
TI  - Assignment of the murine def-3 gene (Rbm6) to chromosome 9F1-F2 and its
      pseudogenes Rbm6-ps1 and Rbm6-ps2 to chromosome 1 by in situ hybridisation.

PMID- 10965134
TI  - Assignment of protein kinase C mu (PRKCM) to human chromosome band 14q11 with
      somatic cell hybrids and radiation hybrids.

PMID- 10965135
TI  - Cloning of the murine Drm gene (Cktsf1b1) and characterization of its oncogene
      suppressible promoter.
AB  - The Drm gene, first identified in rat cells in our laboratory, appears to play a
      significant role in early embryo patterning and limb bud development. We have now
      isolated mouse Drm (mDrm) cDNA as well as genomic DNA clones and have mapped the
      Drm gene (Cktsf1b1) to murine chromosome 2. Cktsf1b1 is regulated in a tissue
      specific fashion and is expressed only in nontransformed mouse cells or primary
      fibroblasts in culture, but not in established transformed or tumor-derived mouse
      cell lines. The major transcription start sites map to within 69 bp upstream of
      the initiating ATG. A promoter was contained in the -214 to +1 bp 5' flanking
      region, and promoter/reporter constructs showed 10-fold higher activity than
      control in REF-1 (rat), A31 (mouse) and CHO (hamster) cells. The region contains
      a TATA sequence and multiple potential transcription factor binding sites.
      Promoter activity was dose-dependently inhibited by cotransfection with either
      ras or mos oncogenes, but oncogene inhibition was reversed and the overall
      activity increased when cells were treated with the MAP kinase kinase (MKK)
      inhibitor PD98059. An NF-1 and Yi-like site, identified in the minimal promoter
      region, showed different mobility shift patterns when normal and transformed cell
      nuclear extracts are compared. Mutation of the NF-1 site reduced Cktsf1b1
      promoter activity 25%, while mutation of the Yi-like site destroyed all the
      activity. Our results indicate that the expression of Cktsf1b1, a gene associated
      with early development and cell transformation, is sensitive to MKK levels and
      may be regulated via multiple transcription factor complexes.

PMID- 10965136
TI  - Sex-specific expression of an evolutionarily conserved male regulatory gene,
      DMRT1, in birds.
AB  - Based on its Z-sex-chromosomal location and its structural homology to male
      sexual regulatory factors in humans (DMRT1 and DMRT2), Drosophila (Dsx), and
      Caenorhabditis elegans (Mab-3), chicken DMRT1 is an excellent candidate for a
      testis-determining factor in birds. The data we present provide further strong
      support for this hypothesis. By whole mount in situ hybridization chicken DMRT1
      is expressed at higher levels in the male than in the female genital ridges
      during early stages of embryogenesis. Its expression becomes testis-specific
      after onset of sexual differentiation. Northern blot and RT PCR analysis showed
      that in adult birds DMRT1 is expressed exclusively in the testis. We propose that
      two gene dosages are required for testis formation in ZZ males, whereas
      expression from a single Z chromosome in ZW females leads to female sexual
      differentiation.

PMID- 10965137
TI  - Assignment of KPNA4 and KPNB1 encoding karyopherin alpha 4 and beta 1 to human
      chromosome bands 11q22 and 17q21 respectively, by in situ hybridization.

PMID- 10965138
TI  - Assignment of the neurofibromatosis 2 (Nf2) gene to rat chromosome bands 14q21-
      >q22 by in situ hybridization.

PMID- 10965139
TI  - Assignment of the Wilms' tumor (Wt1) gene to rat chromosome bands 3q34-->q35 by
      in situ hybridization.

PMID- 10965140
TI  - Genomic structure and chromosome location of the gene encoding mouse CD59.
AB  - The gene encoding the mouse analogue of the human complement regulator CD59 was
      cloned using a combination of long range PCR and genomic library screening.
      Sequence obtained showed that its genomic structure closely resembled that of the
      human CD59 gene, comprising 4 exons, each separated by a long intron region. The
      sizes of introns and exons were comparable to those of the human gene with the
      exception of the third intron which is 2.5 kb in the mouse compared to 7 kb in
      the human gene. All exon/intron boundaries conformed to the GT-AG rules for
      splicing. Radiation hybrid mapping localised mouse Cd59 between D2Mit333 and
      D2Mit127 on chromosome 2, a region homologous with human chromosome 11p13 where
      the human CD59 gene is localised. These data have permitted the construction of a
      gene targeting vector for the generation of transgenic mice deficient in CD59.

PMID- 10965141
TI  - Cloning and characterisation of ITGAV, the genomic sequence for human cell
      adhesion protein (vitronectin) receptor alpha subunit, CD51.
AB  - The integrin family of receptors serves as major receptors for extracellular
      matrix-mediated cell adhesion and migration, cytoskeletal organisation, cell
      proliferation, survival, and differentiation. The alpha-V integrins consist of a
      subset which share a common alpha-V subunit combined with one of five beta
      subunits (beta-1, 3, 5, 6, or 8). The alpha-V integrins have been implicated in a
      number of developmental processes, including vasculogenesis and angiogenesis, and
      are therapeutic targets for inhibition of angiogenesis and osteoporosis. The
      human cDNA for alpha-V integrin (ITGAV) consists of a 5,717-bp transcript with a
      coding sequence (CDS) of 3,146 bp encoding a 150-kDa mature peptide. Here we
      describe the gene structure of ITGAV.

PMID- 10965142
TI  - The gene encoding TBC1D1 with homology to the tre-2/USP6 oncogene, BUB2, and
      cdc16 maps to mouse chromosome 5 and human chromosome 4.
AB  - TBC1D1 is the founding member of a family of related proteins with homology to
      tre-2/UPS6, BUB2, and cdc16 and containing the tbc box motif of 180-220 amino
      acids. This protein family is thought to have a role in differentiation and in
      regulating cell growth. We set out to map the TBC1D1 gene in mouse and human.
      Segregation analysis of a TBC1D1 RFLP in two independent mouse RI (recombinant
      inbred) lines reveals that mouse Tbc1d1 is closely linked to Pgm1 on chromosome
      5. The human TBC1D1 gene was assigned to human chromosome 4p15.1-->4q21 using
      Southern blot analyses of genomic DNAs from rodent-human somatic cell lines. A
      human-specific genomic fragment was observed in the somatic cell lines containing
      human chromosome 4 or the 4p15.1-->4q21 region of the chromosome. TBC1D1 maps to
      the region containing the ortholog of mouse Pgm1 adding another locus to this
      long region of conserved synteny between mouse and man.

PMID- 10965143
TI  - Assignment of the human solute carrier family 4, sodium bicarbonate cotransporter
      like, member 10 gene (SLC4A10) to 2q23-->q24 by in situ hybridization and
      radiation hybrid mapping.

PMID- 10965144
TI  - Assignment of seta to distal mouse X chromosome by radiation hybrid mapping.

PMID- 10965146
TI  - Assignment of the human GABAA receptor delta-subunit gene (GABRD) to chromosome
      band 1p36.3 distal to marker NIB1364 by radiation hybrid mapping.

PMID- 10965145
TI  - Assignment of the NR2E3 gene to mouse chromosome 9 and to human chromosome
      15q22.33-->q23.

PMID- 10965147
TI  - Neuronal and astroglial response to pre- and perinatal exposure to delta-9-tetra-
      hydrocannabinol in the rat substantia nigra.
AB  - The responses of neurons and astroglial cells to pre- and perinatal exposure to
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC) were evaluated in the substantia
      nigra (SN) of male and female rats, at three postnatal ages (PD21, PD30 and
      PD70), by immunohistochemical detection of tyrosine hydroxylase (TH) in
      dopaminergic neurons and of glial fibrillary acidic protein (GFAP) in astrocytes.
      Our results showed that the effects of pre- and perinatal exposure to Delta(9)
      THC on neuronal and astroglial immunoreactivities in the SN (compacta and
      reticulata) varied with sex, with male rats being more susceptible than females.
      Prenatal exposure to Delta(9)-THC decreased TH immunoreactivity in the SN of
      males on PD21 when compared to both their controls and Delta(9)-THC-exposed
      females of the same age. Furthermore, the TH expression decreased with age in
      Delta(9)-THC-exposed males in the SNc pars compacta, whereas it increased in
      controls. On the contrary, TH expression was maintained stable in the SN pars
      compacta of Delta(9)-THC-exposed females from PD21. These differences in neuronal
      development caused by prenatal Delta(9)-THC exposure were associated with
      significant differences in GFAP expression by astroglial cells in both sexes. On
      PD21, GFAP immunoreactivity decreased in the SN in Delta(9)-THC-exposed male
      rats. Although GFAP expression increased in Delta(9)-THC-exposed males with age,
      it did not reach control levels by PD70. On the contrary, significantly increased
      GFAP expression in the Delta(9)-THC-exposed females on PD21 was observed,
      compared to their controls and also to Delta(9)-THC-exposed male rats; however,
      the GFAP expression shown by Delta(9)-THC-exposed females stabilized from PD21.
      These Delta(9)-THC-induced changes in the glial development could indicate that
      Delta(9)-THC accelerated the maturation of astrocytes in female rats, whereas
      Delta(9)-THC delayed astrocytic maturation in Delta(9)-THC-exposed males. These
      findings suggest that pre- and perinatal exposure to Delta(9)-THC can lead to
      long-term effects in both neurons and glial cells.

PMID- 10965148
TI  - Subcellular distribution of pyroglutamyl-peptidase I activity in the developing
      rat cerebellum.
AB  - In this work we analyzed the activity of pyroglutamyl (pGlu)-peptidase I in
      several subcellular fractions of the rat cerebellum during its development. The
      aim of this study is to determine if there is a developmental redistribution of
      this enzyme activity and if this fact could indicate changes in the role of the
      enzyme as age progresses. Results show that pGlu-peptidase I is widely
      distributed, but not homogeneously, in all the subcellular fractions that were
      studied, in both soluble and particulate forms. Significantly the distribution of
      the enzyme changes with development. Thus, in the soluble synaptosomal fraction,
      the pGlu-peptidase I activity is low until PD9 and the activity increases
      significantly from PD9 to PD15, when it reaches adult levels. In contrast, in the
      cytosolic fraction, the pGlu-peptidase I activity is high from fetal day 22 to
      postnatal day 6, and then decreases significantly until postnatal day 90.

PMID- 10965149
TI  - Prenatal expression of the GLUT4 glucose transporter in the mouse.
AB  - The GLUT4 glucose transporter is primarily expressed in skeletal muscle, heart
      and adipose tissue, where its expression is postnatal, coincident with the
      acquisition of insulin-regulated glucose transport. In muscle, contraction also
      regulates GLUT4 activity in the postnatal animal. Here we demonstrate that GLUT4
      is expressed in the developing mouse embryo with specific tissue and
      spatiotemporal patterns. From embryonic day 9 (E9; E1 = day of copulation plug)
      to postnatal day 70 (P70), mice were analyzed for GLUT4 mRNA and protein
      expression by in situ hybridization, immunohistochemistry and immunoblot.
      Specificity was confirmed with sense riboprobe hybridization and peptide
      competition, respectively. At E9, GLUT4 was detected in the cranial neural folds
      in the outer (mantle) layer of the neuroepithelium. At E10, expression was
      present throughout the developing heart and was prominent in the endocardial
      cushions through E12. At E10-12, GLUT4 was also prominent in craniofacial
      mesenchyme. GLUT4 expression in cartilage and bone was evident at E12 and was
      maintained throughout early postnatal life. GLUT4 was apparent throughout
      embryonic development in the ventricular epithelium, choroid plexus and in the
      developing cerebellum. At birth, cardiac expression was reduced and GLUT4 was
      most evident in cartilage, bone and specific brain regions. In the latter, GLUT4
      expression was most evident in the cerebellum, specifically in the external
      granular layer through P7 and in the internal granular layer thereafter. Maximal
      GLUT4 protein levels in the cerebellum were measured between P14 and P21 and were
      reduced in the adult brain. These findings suggest that GLUT4-mediated glucose
      transport may play important roles during development of the brain and
      nonneuronal tissues in the mouse embryo.

PMID- 10965150
TI  - Antisense studies in PC12 cells suggest a role for H218, a sphingosine 1
      phosphate receptor, in growth-factor-induced cell-cell interaction and neurite
      outgrowth.
AB  - Our previous studies of H218, a sphingosine 1-phosphate (S1P) receptor and a
      member of the G-protein-coupled receptor superfamily, suggest that it may
      participate in mammalian nervous system development. Thus, brain levels of H218
      mRNA are higher during early neurogenesis than postnatally. In addition,
      embryonic H218 immunoreactivity is preferentially localized in young neuronal
      cell bodies during their early stages of differentiation and in axons during
      their extension. This report describes the morphological effects of reducing
      native H218 levels in PC12 cells. Western blot analyses demonstrated that PC12
      cells stably transfected with an expression vector carrying an antisense-oriented
      H218 cDNA contain less H218 protein than vector-transfected control cells. When
      differentiated with growth factors, the antisense-H218 cells display more neurite
      production and form less cell-cell contacts than the control cells. Therefore,
      these data, along with our previous H218 expression studies and a recent,
      independent study of H218 overexpression, support the possibility that H218
      contributes to developmental processes regulating neuronal interaction and axon
      growth. The data are also consistent with reports that H218 is a S1P receptor,
      that S1P is present in serum, like that used in our PC12 cell cultures, and that
      it causes PC12 cell neurite retraction. Finally, and in agreement with a S1P
      receptor role for H218, we find that the antisense-H218 cells display less S1P
      induced neurite retraction than control cells.

PMID- 10965151
TI  - Neonatal 6-hydroxydopamine treatment affects GABA(A) receptor subunit expression
      in the frontal cortex but not the hippocampus of rats during postnatal
      development.
AB  - The influence of neonatal administration of 6-hydroxydopamine (6-OHDA) on the
      maturation of GABA(A) receptors in the frontal cortex and hippocampus was studied
      using 5- to 40-day-old rats. In situ hybridization with antisense oligonucleotide
      probes was performed for alpha(1), alpha(2), alpha(5), beta(2), beta(3) and
      gamma(2) subunit mRNAs of the GABA(A) receptor. We demonstrated that neonatal
      treatment with 6-OHDA temporarily delays the postnatal transcription of the
      alpha(1) and gamma(2) subunits in the rat prefrontal cortex, as assessed by in
      situ hybridization histochemistry. The effect was selective for these subunits
      (the alpha(2), alpha(5), beta(2), and beta(3) subunit mRNAs remained unchanged)
      and for this region (the mRNA levels in the hippocampus were not changed). The
      reduction in mRNA levels at early postnatal stages (postnatal day 5, PD5, and
      PD10) also affected the subunit protein levels, as shown by immunohistochemistry
      for the alpha(1) subunit, and the formation of GABA(A) receptor-associated
      picrotoxinin-insensitive TBPS binding sites, as shown by autoradiography. Our
      findings indicate that without a noradrenergic influence, the maturation of
      GABAergic interneurons in the frontal cortex is transiently delayed (from PD5 to
      PD40). However, it is possible that this transient reduction of the expression of
      certain GABA subunits - caused by depletion of noradrenergic innervation - cannot
      cause a lasting alteration to the GABAergic function in the prefrontal cortex.

PMID- 10965152
TI  - PKA phosphorylations on tau: developmental studies in the mouse.
AB  - PKA phosphorylations of tau may be an early event in the development of
      neurofibrillary pathology in Alzheimer's disease. Serines 214 and 409 of tau are
      highly phosphorylated in PHF-tau, but are not phosphorylated to any significant
      extent in normal adult human brain; both of these sites are phosphorylated in
      human fetal tissue. To further study this phenomenon, a developmental
      characterization of these phosphorylation sites relative to PKA, cAMP-dependent
      response binding element (CREB) and phosphorylated CREB was performed using
      samples from mouse brain. Immunoblot analysis using antibodies specific for
      phospho-serine 214 (CP-3) and phospho-serine 409 (PG-5) revealed a marked
      decrease in phosphorylation occurring at each of these sites between postnatal
      day 11 (P11) and P20. Immunoblots with TG-5, a pan-tau antibody, revealed uniform
      expression of tau during postnatal development, as well as a switch in isoform
      composition that is evident between P7 and P11. This switch in isoform
      composition just precedes the change in the extent of phosphorylation at serines
      214 and 409, and occurs at a time when PKA phosphorylation of CREB is increasing.

PMID- 10965153
TI  - Cellular and subcellular localization of necdin in fetal and adult mouse brain.
AB  - Necdin is a 325-amino-acid residue protein encoded by a cDNA clone isolated from
      neurally differentiated embryonal carcinoma cells. Ectopic expression of necdin
      induces growth arrest of proliferative cells. Necdin binds to major transcription
      factors E2F1 and p53, suggesting that necdin exerts its functions through the
      interactions with these cell-cycle-regulating factors. However, information about
      precise localization of endogenous necdin protein is currently lacking. A rabbit
      polyclonal antibody was raised against a bacterially expressed recombinant
      protein of necdin (amino acids 83-325). Immunoblot analysis revealed that necdin
      protein was expressed almost exclusively in the brain of adult mice. A relative
      molecular mass of endogenous necdin was estimated at approximately 43,000. In
      developing mouse brain, necdin was most abundant during fetal and neonatal
      periods. Necdin was highly enriched in the cytoplasm of hypothalamic neurons in
      fetal and adult mice. The subcellular fractionation analysis revealed that necdin
      was concentrated in the cytosol fraction of brain cells. These results suggest
      that endogenous necdin protein is localized predominantly in the cytoplasm of
      differentiated neurons and moves into the nucleus under specific conditions.

PMID- 10965154
TI  - Dendritic alterations of cerebellar Purkinje neurons in postnatally lead-exposed
      kittens.
AB  - Many investigations have sought to determine the effect of lead exposure on the
      development of the cerebellum. This study addresses the effects of postnatal lead
      exposure in kittens on dendritic development of Purkinje cells. Golgi-Cox filled
      cells were used to measure dendritic branching patterns, spine density, height,
      width and distance from the cerebellar surface. The results revealed a
      significant increase in spine density and altered patterns of dendritic
      branching. Complex dendritic branching was evident with a progressive shift in
      peak branching peripherally. Lead-exposed Purkinje cells showed early sprouting
      with subsequent pruning. At 5 weeks of age dendritic branches on experimental
      cells were increased along the entire dendritic extent. Control Purkinje cells
      showed initial sprouting with subsequent pruning. Normal developmental growth
      spurts and lead-induced effects were evident on dendritic height, width and
      distance from the surface. Cerebella stained with hematoxylin and eosin and
      cresyl violet acetate showed no evidence of vascular damage or other pathologies.
      These findings corroborate the evidence of hyperspiny dendritic formation
      representing an important mechanism of neuronal plasticity. In regard to
      morphological effects of lead on rodents, the hyperspiny Purkinje cell dendrites
      and patterns of dendritic growth in lead-treated kittens offer an alternative
      interpretation of neurobehavioral findings of lead-burdened children. The results
      are discussed with reference to other aspects of lead exposure and neural
      development.

PMID- 10965155
TI  - Striatal ionotropic glutamate receptor ontogeny in the rat.
AB  - Rat striatal N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) and kainate (KA) receptor staining were evaluated
      postnatally in the rat. Immunohistochemistry was used to detect subunit proteins
      of the three glutamate receptor subtypes. The glutamate receptors displayed
      distinct developmental expression patterns in the striatum. Morphological
      distributions for the NMDA R1 subunit (representative of NMDA receptors), Glu R1
      and Glu R2/3 subunits (indicative of AMPA receptors), and Glu R5/6/7 subunits
      (demonstrating KA receptors) attained adult expression patterns and levels at
      different postnatal time points. The ontogenic maturation sequence of striatal
      glutamate receptor expression was KA, then AMPA and lastly NMDA. Staining
      patterns for NMDA and AMPA subunit proteins were detected initially as dense
      patches in the neuropil, which changed to a homogeneous stain of the striatum by
      the second week of life. Cellular staining for the three subtypes was intense
      within the highly reactive neuropil patches, but less intensely stained in
      neurons located outside these zones. The KA receptor subunit did not exhibit
      neuropil heterogeneity, but was distributed evenly at birth. All three glutamate
      receptor subtypes were visible within the striatal neuron populations.
      Populations of striatal neurons that expressed the three differential glutamate
      receptor subtypes overlap, exhibit different growth patterns and dendritic
      staining. These results support a functional emergence of different glutamate
      receptor activation within the striatum and provide a potential therapeutic means
      to isolate developmental disorders specifically associated with excitatory
      circuits of the basal ganglia.

PMID- 10965157
TI  - Slowed reaction time in HIV-1-seropositive intravenous drug users without AIDS.
AB  - One hundred and fourteen subjects with a history of intravenous drug abuse (65
      subjects infected with the human immunodeficiency virus, HIV, and 49 seronegative
      controls) were evaluated with a reaction time (RT) test which included one
      measure of simple RT and three measures of complex RT. All seropositive patients
      were in HIV stages A or B. The multivariate analysis of covariance controlled for
      age, educational level and Montgomery-Asberg Depression Rating Scale score,
      showed differences between seropositive subjects and controls: the seropositive
      group scored slower than the control group on two RT tasks, simple RT and a more
      complex RT measure. Our results suggest that computerized RT measures may be more
      sensitive than conventional neuropsychological tests in detecting subtle
      cognitive and motor retardation in the early stages of HIV infection, thus
      extending the findings of other studies to the intravenous drug-user population.

PMID- 10965156
TI  - Somesthetic disconnection syndromes in patients with callosal lesions.
AB  - Somesthetic disconnection syndromes were investigated in relation to the sites of
      lesions in the corpus callosum in 3 patients with callosal lesions, in order to
      identify the callosal regions responsible for the interhemispheric transfer of
      somesthetic information. Cases 1 and 2 with lesions in the posterior truncus
      exhibited transfer deficits of discriminative sensations between the left and
      right hands, left-sided tactile anomia and left-sided somesthetic alexia. Case 3
      with lesions in the posteroventral part of the posterior truncus showed no signs
      of somesthetic disconnection syndromes. The results suggest the importance of the
      anterior and/or dorsal part of the posterior truncus of the corpus callosum for
      interhemispheric transfer of the discriminative sensations and integrated
      somesthetic information necessary for tactile naming and somesthetic reading.

PMID- 10965158
TI  - Miller fisher syndrome: a hospital-based retrospective study.
AB  - Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and
      ophthalmoplegia, is generally considered as a variant of Guillain-Barre syndrome
      (GBS). However, some investigators believed that the syndrome could be explained
      by a central origin. To obtain more information about MFS for comparison with
      GBS, we conducted a retrospective study by analyzing the clinical data of MFS
      patients admitted to our hospital over a period of 11 years. The calibrated
      male/female ratio was 1.65. A seasonal clustering in winter was noted. The
      percentage of MFS among GBS was especially high (18%, 11/60) in Taiwan when
      compared with other series. Involvement of limb muscle strength, autonomic
      function and cranial nerves, except ocular motor nerves, was rarely found in our
      patients. When MFS is accompanied by limb weakness, it might represent a
      transitional form between MFS and GBS. Bulbar palsy and dysautonomia might
      predict a relatively poor prognosis. To obtain more reliable information, lumbar
      puncture should be done 1 week after disease onset, and electrophysiological
      tests should be done serially in every MFS patient. Eighty percent (80%, 4/5) of
      our patients were positive for IgG anti-GQ(1b) antibody activity. In our study,
      there is more evidence indicating that MFS is a peripheral nervous system
      disorder; however, no definite conclusion could be made as to whether MFS is
      exclusively a peripheral or central nervous system disorder. We think MFS is an
      immune-mediated clinical entity which mainly involves the peripheral nervous
      system with rare involvement of other parts of the central nervous system.

PMID- 10965159
TI  - Loss of left-sided volitional movements caused by a combined lesion of the corpus
      callosum and right hemisphere:'initiation pseudohemiakinesia'.
AB  - We report a right-handed patient who showed a marked loss of unilateral
      volitional movements of the left limbs after the onset of a cerebral infarction
      in the combined territories of the right anterior and middle cerebral arteries.
      The same limbs retained their mobility in acts requiring bilateral sides of the
      body. This left-sided abnormal behavior resembled motor neglect resulting from
      lateralized brain damage. Behavioral and neuroradiological findings presented by
      this patient, however, suggested that callosal disconnection was definitely
      involved in this symptomatology. We postulate that in this patient, the diseased
      right hemisphere could no longer initiate movements of the left limbs despite its
      potential ability to realize them, and that the injured callosum prevented the
      intact left hemisphere from initiating unilateral voluntary movements of the left
      limbs. We suggest that this so far undescribed symptomatology be called
      'initiation pseudohemiakinesia' in order to be distinguished from other rare
      forms of unilateral voluntary movements like motor neglect, extinction or
      directional hypokinesia.

PMID- 10965160
TI  - Polymorphisms of the parkin gene in sporadic Parkinson's disease among Chinese in
      Taiwan.
AB  - The role of genetics in Parkinson's disease (PD), previously controversial, is
      now documented by several studies. A major breakthrough has been the discovery of
      two single-gene defects in familial PD. A single base pair change at position 209
      from G to A (G209A) in the fourth exon of the alpha-synuclein gene has been
      identified in cases of autosomal dominant familial PD. Mutations in the Parkin
      gene can induce autosomal recessive juvenile parkinsonism. A polymorphism of
      R/W366 in the Parkin gene was found to be associated with a protective factor for
      sporadic PD. We surveyed the polymorphisms of the Parkin gene, including S/N167,
      R/W366 and V/L380, in 92 cases of sporadic PD and 98 nonaffected individuals in
      Taiwanese Chinese. The allele frequencies of these polymorphisms are not
      significantly different between PD and nonaffected controls. We conclude that
      polymorphisms of the Parkin gene, S/N167, R/W366, V/L380, are not genetic factors
      for sporadic PD among Chinese in Taiwan.

PMID- 10965162
TI  - Prevalence of arylsulfatase A pseudodeficiency allele in metachromatic
      leukodystrophy patients from Poland.
AB  - Arylsulfatase A (ASA) pseudodeficiency (PD) allele was searched for in 22
      patients originating from Poland and suffering from different types of
      metachromatic leukodystrophy (MLD). Four of them carried the PD allele in a
      heterozygous state. The prevalence of the PD allele among investigated MLD
      patients was revealed to be 9%, while the frequency of the PD allele in healthy
      controls was estimated at 6-7%. One of the examined MLD patients was additionally
      a carrier of an isolated mutation leading to the loss of the N-glycosylation
      site. The question arises whether and how MLD mutations create a convenient
      milieu for PD mutations to occur (or inversely).

PMID- 10965161
TI  - Effect of tolcapone on the haemodynamic effects and tolerability of desipramine.
AB  - BACKGROUND AND PURPOSE: To determine the changes in haemodynamics, tolerability
      and pharmacokinetics that may occur when a combination of tolcapone and
      levodopa/carbidopa are given with desipramine. METHODS: In a crossover study, 22
      healthy subjects received desipramine during two 13-day treatment periods (25 mg
      t.i.d. for 3 days and 50 mg t.i.d. for 10 days), with a washout period of 10-15
      days. Subjects received levodopa/carbidopa (100 mg/25 mg t.i.d. for 5 days, days
      9-13) and concomitant, double-blind, randomized treatment with either tolcapone
      (200 mg t.i.d.) or placebo. RESULTS: No significant pharmacodynamic and
      pharmacokinetic interactions occurred between tolcapone and desipramine. Adverse
      events were predictable based on the known effects of the individual drugs.
      CONCLUSIONS: Tolcapone can be combined with levodopa/carbidopa and desipramine in
      patients with Parkinson's disease.

PMID- 10965163
TI  - The serotonin transporter gene and Parkinson's disease.
AB  - Dysfunction in the serotonin (5-hydroxytryptamine) system and reduced serotonin
      concentrations have been reported in patients with Parkinson's disease (PD).
      Serotonin concentrations in neural tissue are controlled by a presynaptic
      serotonin transporter protein that is encoded by a single gene. Therefore, we
      investigated whether a polymorphic region in the serotonin transporter gene is
      associated with PD. Three variable-number tandem repeat (VNTR) elements of the
      serotonin transporter gene were detected by polymerase chain reaction, those with
      9, 10, 11 and 12 copies of the repeat element. The 10-copy VNTR element was
      significantly less common in patients with PD than controls in the univariate
      analysis (p < 0.05). Logistic regression analysis revealed no significant
      differences between patients (n = 198) and controls (n = 200) in the distribution
      frequencies of 9- and 12-copy alleles and combined genotypes (odds ratio = 1.20;
      p = 1.71). A positive family history of PD was a strong predictor of disease risk
      (odds ratio = 2.98; 95% confidence interval 1.51-5.87; p = 0.001). Although
      slight differences were observed between patient and control groups, these data
      suggest that defects in serotonin concentrations in patients with PD are unlikely
      to be due to polymorphisms in the serotonin transporter gene in this large
      Australian cohort; however, the inverse association observed with the 10-copy
      allele warrants further investigation.

PMID- 10965164
TI  - Cardiac autonomic function in patients suffering from primary focal
      hyperhidrosis.
AB  - Cardiac autonomic function in patients (n = 63) with primary focal hyperhidrosis
      and healthy controls (n = 28) was investigated by short-term frequency domain
      power spectral analysis of heart rate variability. The power of the very-low
      frequency band (0.01-0.05 Hz) was significantly lower in patients with axillary
      hyperhidrosis than in controls. No differences between groups could be observed
      at investigation of the low-frequency band (0.05-0.15 Hz), which was a surprising
      finding because this band represents also sympathetic cardiac innervation. At the
      high-frequency band (0.15-0.5 Hz), which represents parasympathetic cardiac
      innervation, an interaction of type and position influencing spectral power was
      detected. Our highly interesting findings indicate that primary focal
      hyperhidrosis is based on a much more complex autonomic dysfunction than
      generalised sympathetic overactivity and seems to involve the parasympathetic
      nervous system as well.

PMID- 10965165
TI  - Conduction block of the ulnar nerve in cervical dystonia.

PMID- 10965166
TI  - Early detection of small pontine infarction presenting cheiro-oral-pedal syndrome
      by diffusion-weighted magnetic resonance imaging.

PMID- 10965167
TI  - Sensory neuropathy due to Bajiaolian (Podophyllotoxin) intoxication.

PMID- 10965168
TI  - Cerebrocutaneous xanthoma disseminatum and disseminated demyelinating
      encephalomyelitis.

PMID- 10965169
TI  - A case of pectoral fasciitis with spontaneous remission.

PMID- 10965170
TI  - Creutzfeldt-Jakob disease presenting as isolated dysarthria and dysphagia due to
      pseudobulbar palsy.

PMID- 10965171
TI  - Oromandibular dystonia in a patient with bilateral putaminal necrosis after
      methanol poisoning: an electrophysiological study.

PMID- 10965172
TI  - Intravenous methylprednisolone for aseptic meningitis in Vogt-Koyanagi-Harada
      syndrome.

PMID- 10965173
TI  - Reply to the letter by solaro and messmer uccelli concerning the article by
      finsterer and lubec: 'Persistent aseptic meningitis in vogt-koyanagi-harada
      Syndrome'

PMID- 10965174
TI  - Effect of speaking rate manipulations on acoustic and perceptual aspects of the
      dysarthria in amyotrophic lateral sclerosis.
AB  - The current study explored the acoustic and perceptual effects of speaking rate
      adjustments in persons with amyotrophic lateral sclerosis (ALS) and in
      neurologically normal individuals. Sentence utterances were obtained from the
      participants at two self-selected speaking rates: habitual and fast. Total
      utterance durations, segment durations, and vowel formant frequencies comprised
      the acoustic measures, whereas magnitude estimates of speech intelligibility and
      severity of speech involvement were the perceptual measures. Results showed that
      participants in both the neurologically normal and ALS groups were able to
      increase their speaking rate when asked to do so, but that the participants with
      ALS were significantly slower than the neurologically normal participants at both
      rates. Both groups of participants also showed compression of the acoustic vowel
      space with increased speaking rate, with the vowel spaces of participants with
      ALS generally being more compressed than the vowel spaces of neurologically
      normal participants, at either rate. Most importantly, the perceptual measures
      failed to show any effect of the speaking rate adjustment on scaled
      intelligibility or severity, for either group. These findings are discussed
      relative to the general issue of slow habitual speaking rates among many speakers
      with dysarthria, and possible explanations for the slowness. The lack of an
      effect of increased rate on the perception of the speech deficit among speakers
      with ALS argues against the idea that the habitually slow rates are a form of
      compensation to reduce the complexity of speech production.

PMID- 10965175
TI  - Speech therapy in the management of male-to-female transsexuals.
AB  - This article discusses communication problems of transsexuals and gives an
      example of phoniatric and logopedic assessment as well as a possible 'prototype'
      of speech therapy with male-to-female transsexuals.

PMID- 10965176
TI  - Temporal speech characteristics of individuals with multiple sclerosis and ataxic
      dysarthria: 'scanning speech' revisited.
AB  - 'Scanning speech' has been used as a description of a prominent characteristic of
      the dysarthria of multiple sclerosis (MS) as well as of ataxic dysarthria in
      general. It is thought to be measurable as equalized syllable durations. There
      are seemingly contradictory prosodic-temporal characteristics of ataxic
      dysarthria: perceptually characterised as prosodic excess as well as phonatory
      prosodic insufficiency and acoustic characteristics including signs of isochrony
      as well as variability. This study investigates the temporal characteristics at
      two levels, duration and variability of syllable durations and the durations of
      interstress intervals. A group of 14 individuals with MS and ataxic dysarthria as
      well as 15 control subjects were studied. It was concluded that individuals with
      ataxic dysarthria and MS showed (a) for syllables: significantly increased
      durations and decreased intrautterance variability (more isochrony or syllable
      equalization) as well as significantly increased interutterance variability; (b)
      for interstress intervals: significantly increased durations and increased
      variability (less isochrony). The results point to inflexibility as well as
      instability of temporal control, which could contribute to the explanation of why
      the perceptual characteristics are contradictory.

PMID- 10965177
TI  - The number of therapeutic sessions in logopedic care: a description and analysis.
AB  - The aim of this study was (i) to describe the number of therapeutic sessions in
      logopedic care in the Netherlands and (ii) to analyse which factors determine the
      number of sessions. An analysis was performed on a data set of 517 patients who
      received logopedic treatment. Data concerning patient characteristics, medical
      diagnosis, logopedic diagnosis (in terms of impairments, disabilities and
      handicaps) and the number of sessions were available. The mean number of sessions
      was 17.2 (SD 10.7). In a multivariate analysis 19.4% of the total amount of
      variance in the number of sessions was explained; impairments were the only
      significant determinant. Language development impairments, aural impairments and
      impairments of auditory functions were associated with a relatively large number
      of sessions; impairments in reading and writing were associated with relatively
      few sessions. Recommendations for the design of future studies on the optimal
      number of sessions are derived from these findings.

PMID- 10965178
TI  - Pain and Alzheimer's disease.
AB  - Literature on pain management in Alzheimer's disease is slowly emerging and this
      review deals with different aspects of pain in this growing population. Clinical
      pain, experimental pain and assessment of pain in cognitively impaired patients
      are presented. Treatment of pain is also discussed. This review calls for more
      studies and clinical trials with a view to improve the comfort and quality of
      life of patients suffering from Alzheimer's disease.

PMID- 10965179
TI  - Immunophenotypical changes of T lymphocytes in the elderly.
AB  - BACKGROUND: Substantial changes in both representation and function of T
      lymphocyte subsets have been reported with advancing age. However, till now, no
      systematic studies focused on age-dependent changes in the expression intensity
      of the major T lymphocyte surface receptors. OBJECTIVE: The present study was
      undertaken in order to establish age-related differences in lymphocyte
      subpopulations by simultaneously measuring three surface antigens in young and
      elderly people. METHOD: Peripheral blood T cell subsets from 20 healthy elderly
      individuals and 15 healthy young adult donors were examined by means of a
      quantitative three-color flow cytometry method. RESULTS: Activated (HLA-DR+) and
      memory (CD45RO+) T cells, CD3+CD7- T lymphocytes, and cells expressing natural
      killer (NK) markers (CD3-CD56+ NK cells and CD3+CD56+ T lymphocytes) were
      expanded, whereas T lymphocytes expressing the adhesion molecule CD62L were lower
      in elderly compared with young donors. In addition to alterations in the
      percentages of T cell subsets during senescence, several changes in the intensity
      expression of T cell antigens were also detected. CD3 antigen expression was
      downregulated on total T lymphocytes as well as on the memory T cell subset,
      while CD56+ T cells exhibited increased CD3 levels. Moreover, CD2 expression,
      unchanged on NK cells, was upregulated on T lymphocytes from elderly subjects.
      CD3+CD7- T cells exhibited increased expression of CD8 antigen, while the
      intensity expression of HLA-DR on activated T cells and CD7 on both T and NK
      lymphocytes was decreased. T cells from elderly subjects also exhibited higher
      expression of CD50 and CD62L adhesion molecules as compared with young ones.
      CONCLUSION: These T cell antigen expression modulations during senescence, in
      addition to the alteration in the frequency of the various T lymphocyte subsets,
      could contribute to the complex remodeling of the immune function characteristic
      of the elderly.

PMID- 10965180
TI  - Muscle strength and mass of lower extremities in relation to functional abilities
      in elderly adults.
AB  - BACKGROUND: Functional and physiological declines in advancing age may be
      significant limiting factors in reduced physical activity. Sarcopenia of aging,
      as a normative process or disease, cannot entirely explain reduced physical
      activity in the elderly. OBJECTIVE: The purpose of the study was to investigate
      the relationship between muscle loss and reduction in functional abilities in
      elderly adults and also to determine whether an exercise program can improve
      functional performance and muscle quality. METHODS: Anthropometric measurements
      and sensorimotor testing were conducted on 28 volunteers (12 men and 16 women,
      82.7 +/- 2.4 years of age) who were permanent residents in a skilled nursing
      facility. Twenty-nine elderly adults (79.3 +/- 3.5 years of age) served as a
      control, nonexercising group. Anthropometric measurements included: weight,
      height, body fat, and thigh circumference. The muscle strength was tested with a
      medical isokinetic system. We assessed two sensorimotor functions including a
      'timed up-and-go' test and a 3-min distance walking test. The institutionalized
      participants undertook an exercise training program lasting 12 weeks. RESULTS: No
      significant changes were observed in thigh circumference, body weight, or
      percentage of body fat in either gender as a result of the exercise training. An
      improvement in muscle strength was noticed in 82% of the relatively younger group
      (79-83 years of age) under a slow voluntary contraction at 60 degrees /s (p <
      0.05). Post-training results showed a significant improvement in performance in
      the two sensorimotor tests (p < 0.05). The correlation coefficients between
      muscle strength and functional ability were weak: r = 0.60 and r = 0. 57 for
      males and females, respectively. CONCLUSIONS: This study confirmed the positive
      effects of an exercise program on functional performance in older adults. The
      improvement in functional abilities did not correlate with muscle strength, body
      weight, or body fat.

PMID- 10965181
TI  - Influence of cognitive status on the sexual life of 352 elderly Italians aged 65
      105 years.
AB  - BACKGROUND: Various factors are considered to influence sexual behavior in the
      elderly, but the role played by preservation of adequate cognitive functioning
      has not been adequately explored. OBJECTIVE: The aim of this research, conducted
      on 352 older adults aged between 65 and 105 years, was to identify the specific
      role played by cognitive functioning in sexual activity and sexual interest in
      the elderly. METHODS: The data were collected from elderly people attending the
      surgeries of 21 general practitioners in the city of Padua (Italy). Analysis of
      sexual functioning was based on two items, from the LEIPAD questionnaire: 'Are
      you interested in sex?' and 'Do you have sexual relations?'. Subjects cognitive
      status was assessed objectively through the Mini Mental State Examination (MMSE)
      and subjectively by the LEIPAD subscale on cognitive functioning. RESULTS:
      Subjects who were sexually active and interested in sex were more highly
      represented among the married elderly. The elderly who reported being active and
      interested in sex were significantly younger and had a significantly superior
      educational level and MMSE score. Mean scores for cognitive functioning and all
      quality-of-life indicators were in general significantly better for the active
      and interested. Univariate logistic regression analysis indicated that a higher
      MMSE score and cognitive functioning score influenced the maintenance of sexual
      interest. CONCLUSIONS: One third of the subjects reported being still sexually
      active and 40% being still interested in sex. This study seems to suggest that a
      significant role may be played by cognitive functioning in the maintenance of
      sexual interest in the elderly, especially older females in whom this dimension
      is evidently linked to far more diversified experiences than their male peers.

PMID- 10965182
TI  - Role of physical activity training in attenuation of height loss through aging.
AB  - BACKGROUND: Although the genetic contribution to variability in bone mass has
      been estimated to be as high as 80%, evidence continues to accumulate suggesting
      that factors such as physical activity can influence bone mass which may avoid
      compression of the vertebrae leading to slower stature decline with age.
      OBJECTIVES: This study examines whether regular exercise has the potential of
      positively affecting the aging process with regard to height loss. METHODS: The
      height of 957 females and 1,088 males who were 35-55 years of age in 1965 were
      measured again in 1995. Based on a questionnaire, the subjects were divided into
      four groups. Group A (80 females, aged 73. 2 +/- 6 years, and 141 males, aged
      72.1 +/- 5.7 years) represented subjects who were engaged in moderate vigorous
      aerobic activity throughout their lives; group B (95 females, aged 73.6 +/- 5.5
      years, and 207 males, aged 71.7 +/- 6.1 years) were subjects who started their
      moderate vigorous aerobic activity around the age of 40 and kept their activity
      until the present time; group C (362 females, aged 73.2 +/- 5 years, and 390
      males, aged 71.1 +/- 6 years) were persons who were active as young adults, but
      did not continue to exercise, and group D (425 females, aged 72.8 +/- 5.3 years,
      and 350 males, aged 70.9 +/- 6.1 years) were subjects who had not exercised
      regularly throughout their lives. RESULTS: All subjects lost height due to aging.
      However, significant (p < 0.05) differences in rate of height loss were found
      among the A, B, C, and D groups: for females 3.4 +/- 0.7, 3.5 +/- 0.8, 6.0 +/-
      0.5, and 6.5 +/- 0.7 cm, respectively; for males 2.6 +/- 0.5, 3.1 +/- 0.4, 5.3 +/
      0.4, and 5. 5 +/- 0.5 cm, respectively. In addition, the females' height loss
      rate was significantly (p < 0.05) higher than that of the males in all four
      activity categories. CONCLUSIONS: These data suggest that lifelong moderate
      endurance training, especially after the age of 40 years, is associated with
      attenuation of height loss in both sexes. However, the magnitude of the
      attenuation is significantly higher in males.

PMID- 10965183
TI  - Peptic ulcer in the very old patients.
AB  - OBJECTIVE: To describe the clinical features of peptic ulcer in patients aged 80
      years or over. DESIGN: The patient files of 73 ulcer patients were
      retrospectively analyzed. RESULTS: Peptic ulcer was found in 17% of the
      gastroscopies made on patients aged 80 years or over. Epigastric pain was the
      most common symptom (74%). Vomiting and nausea were also common symptoms. 48% of
      the ulcers were duodenal and 52% gastric. The majority (65%) of ulcers were
      Helicobacter pylori negative. H.-pylori-positive patients used acetylsalicylic
      acid more frequently than the H.-pylori-negative (57 vs. 43%) ones. Complications
      occured in 69% of the patients. Aspirin and nonsteroidal anti-inflammatory drug
      (NSAID) users had more often complications than the others. CONCLUSIONS: Peptic
      ulcer is a common clinical finding of gastroscopy in patients aged 80 years or
      over. Most ulcers are H.-pylori-negative and almost evenly divided between
      duodenal and gastric ulcers. Most of the elderly patients suffer from epigastric
      pain. Complications are frequent among the patients, especially in aspirin and
      NSAIDs users. H.-pylori-infected aspirin users are at increased risk of ulcer
      disease. Before starting long-term aspirin treatment in elderly patients,
      eradication of H. -pylori is recommended.

PMID- 10965184
TI  - Are changes in sensory disability, reaction time, and grip strength associated
      with changes in memory and crystallized Intelligence? A longitudinal analysis in
      an elderly community sample.
AB  - BACKGROUND: Little is known about predictors of cognitive changes in the elderly.
      Sensory disability, grip strength, and speed of processing have been established
      as associates of cognitive performance in cross-sectional studies. However, it is
      not known whether changes in these predictor variables are associated with
      changes in cognitive functioning. OBJECTIVES: (1) to examine the relationship
      between initial level of three predictor variables - speed of processing, sensory
      disability, and grip strength - and changes in memory and crystallized
      intelligence (CIQ); (2) to examine the relationships between change in grip
      strength, cognitive speed, and sensory disability and changes in memory and CIQ,
      and (3) to investigate these relationships with the effects of age and sex
      statistically removed. METHODS: Cognitive ability was assessed in two domains:
      CIQ (3 tests) and memory (3 tests) measured on two occasions approximately three
      and a half years apart in a large community sample (n = 425; mean age = 75.8,
      range 70-93 years). Repeated-measures Anova was used to analyze descriptive data.
      Latent-change models were used to examine structural relationships between
      constructs. RESULTS: Initial levels of reaction time or grip strength did not
      predict rate of change on memory tasks. Changes in grip strength, speed, and
      memory correlated moderately, suggesting that these variables have some tendency
      to move together over time. Sensory disability correlated with age but not with
      change in speed, grip, memory, or CIQ. These relationships held across the age
      range studied after adjustment for age and sex. CONCLUSIONS: The findings are
      consistent with the action of a common causal mechanism underlying changes in
      speed, grip, and memory. A number of methodological caveats arise from our
      analysis. Cross-sectional and longitudinal data sets yield different
      interpretations about the basic component associates of cognitive performance.

PMID- 10965185
TI  - Clinical relevance of thiamine status amongst hospitalized elderly patients.

PMID- 10965186
TI  - Transvaginal sonohysterography for the evaluation and treatment of retained
      products of conception.
AB  - Diagnosing retained products of conception in a woman presenting with postpartum
      or postabortion bleeding presents a clinical challenge. Although ultrasonographic
      examination may be potentially useful in detecting retained products of
      conception, its accuracy has not yet been established. Saline infusion
      sonohysterography is a simple ultrasonographic technique for enhanced
      transvaginal sonographic imaging of the endometrial cavity by the instillation of
      saline into the uterine cavity during ultrasonographic evaluation. This technique
      enhanced our ability to diagnose retained products of conception, and we describe
      our experience in evacuating them under sonographic guidance while performing
      saline infusion sonohysterography.

PMID- 10965188
TI  - Placental apoptosis in normal and abnormal pregnancies.
AB  - The aim of this study was to demonstrate apoptosis in the human placenta in
      normal and abnormal pregnancies. The percentage of apoptotic cells in placental
      samples was quantified by analyzing the cell cycle of nuclei stained with
      propidium iodide using a flow cytometer. No significant difference in the
      percentage of apoptotic cells was observed comparing the group of normal
      pregnancies (first and second trimesters) with those of missed abortions. There
      was also no difference in the incidence of apoptosis comparing placental samples
      obtained from chromosomally normal and abnormal pregnancies. Yet, there was a
      significant increase in the incidence of apoptosis in placental samples obtained
      from second and third trimesters as compared with those obtained from the first
      trimester (p<0.04 and p<0.01, respectively). There was also a significant
      increase in the incidence of placental apoptosis in the third as compared with
      the second trimester (p<0.03).

PMID- 10965187
TI  - 5-hydroxytryptamine induces vasoconstriction of the human umbilical artery:
      effects of hypoxia and nicorandil.
AB  - Human umbilical arteries are known to be modulated by oxygen partial pressure. To
      further understand the underlying mechanisms, rings were suspended in organ
      chambers for the measurement of isometric force. The effects of 5
      hydroxytryptamine (10(-9) to 10(-5) M) were first investigated before and after
      hypoxic conditions (5% O(2)-5% CO(2) in N(2)). Then after pretreatment, we tested
      indomethacin (10(-5) M), N-nitro-L-arginine (L-NNA, 10(-5) M) and nicorandil (10(
      5) M) each separately, then each of the three substances together with hypoxia.
      In separate experiments the contractions to 5-hydroxytryptamine (10(-9) to 10(-5)
      M) were effectuated in a glucose-free medium, and mitochondrial respiration was
      inhibited by cyanide (2 mM). Hypoxic conditions significantly reduced the
      contractive response to 5-hydroxytryptamine. Contractions were enhanced after
      indomethacin, but remained unchanged after L-NNA. Pretreatment with nicorandil
      decreased the contraction. Furthermore, hypoxia and nicorandil dramatically
      decreased the contraction to 5-hydroxytryptamine. In glucose-free medium under
      normoxia or in hypoxic conditions, 5-hydroxytryptamine did not induce any
      contraction. Moreover, cyanide (2 mM) remained without effect on the contraction
      obtained by 5-hydroxytryptamine. These results suggest that hypoxia and
      nicorandil attenuate vasoconstrictor responses to 5-hydroxytryptamine in human
      umbilical arteries. Furthermore, these findings suggest that prostacyclin acts as
      a functional antagonist to vasoconstriction whereas nitric oxide does not.
      Finally, glycolysis seems to be involved rather than mitochondrial metabolism.

PMID- 10965190
TI  - Chronic intrauterine bleeding and fetal growth at less than 32 weeks of
      gestation.
AB  - Placental hemosiderin deposition representing intrauterine bleeding at least 24
      48 h before delivery is detected frequently in prematurity. The objective of this
      study was to assess incidence and site of histologic evidence of intrauterine
      bleeding in association with fetal growth in prematurity. Placentas of
      consecutive nonanomalous singleton liveborns delivered <32 weeks of gestation
      were studied for the presence of hemosiderin in decidua of the placental basal
      plate or extraplacental membranes (confirmed by Prussian blue stain). Cases of
      placenta previa, clinical abruption, or coagulopathy and cases in whom obstetric
      and neonatal gestational age assessment differed by >2 weeks were excluded. A
      single reviewer blinded to clinical data except for gestational age at delivery
      assessed the presence of decidual hemosiderin. Statistical analysis included
      ANOVA, and Mann-Whitney U test with p<0.05 considered significant. The study
      included 352 patients delivered for principal indication of premature rupture of
      membranes (PROM) or preterm labor (PTL) and 78 patients delivered for
      preeclampsia between 1989 and 1994. Mean birth weight percentiles for neonates
      delivered following PROM/PTL versus preeclampsia were: no decidual hemosiderin
      42+/-25 versus 17.4 +/-25, extraplacental membrane hemosiderin 42+/-25 versus 9.2
      +/-10, placental basal plate hemosiderin 42+/-25 versus 17+/-24, and hemosiderin
      in both sites 27+/-21 versus 6.4+/-10 (p = 0.02). Hemosiderin deposition in both
      placental basal plate and extraplacental decidua is associated with significantly
      lower mean birth weight percentiles in PROM/PTL at less than 32 weeks of
      gestation. We postulate that in these patients placental disruption which
      accompanies decidual bleeding may explain the relatively impaired fetal growth.
      In preeclampsia, hemosiderin depositions are not associated with further impaired
      fetal growth.

PMID- 10965189
TI  - Apoptosis in human term placenta. A morphological and gene expression study.
AB  - The objective of this study was to examine placentas after delivery from normal,
      healthy patients at term gestation. The placentas were from elective cesarean
      sections (n = 10, prior to the onset of labor) and spontaneous vaginal delivery
      (n = 10, after labor). We found that deoxyribonucleic acid laddering was present
      in all placentas and consistent with the pattern found in tissues that undergo
      apoptosis. Paraffin-embedded sections of placental villi stained by the in situ
      terminal deoxynucleotidyl transferase mediated biotinylated dUTP nick end
      labeling method revealed positive apoptotic nuclei in the placental villi.
      Reverse-transcriptase polymerase chain reaction demonstrated expression of
      messenger RNA for testosterone-repressed prostate message 2 and B cell
      lymphoma/leukemia-2 in the placenta. Our data demonstrate that apoptosis occurs
      in human term placenta.

PMID- 10965191
TI  - The outcome of triplet versus twin pregnancies.
AB  - OBJECTIVE: The purpose of this study was to examine and to determine whether
      triplet pregnancies are associated with a significantly greater risk of adverse
      outcome than are twin pregnancies. METHODS: Maternal and perinatal outcomes were
      evaluated retrospectively in 41 sets of triplets and twin pregnancies that were
      matched for maternal age, parity, mode of delivery, preterm delivery, mode of
      conception, and antepartum complications. MAIN OUTCOME MEASURES: Perinatal
      outcome in triplet versus twin gestation. RESULTS: Triplets had a significantly
      lower mean average birth weight than in twin gestation (1,596 vs. 2,317 g,
      p<0.018) and gestational age at delivery (32.9 vs. 35.9 weeks; p< 0.03). Preterm
      labour occurred significantly more often in triplet than in twin gestation (80.5
      vs. 41.5%) as did preterm delivery (87.8 vs. 46.2%). Triplets required a longer
      hospital stay than did twins (25 vs. 9 days; p<0.04). There were no significant
      differences between the groups in number of administrations to the Special Care
      Baby Unit (32.5 vs. 30.5%). Apgar score <7 at 5 min was significantly more in
      triplet as compared with twin gestation (17 vs. 6%; p<0.0015). Neonatal deaths
      occurred significantly more in triplets than in twins (26 vs. 8.5%; p< 0.0001).
      There were no significant differences between the groups in maternal antepartum
      or neonatal complications such as anaemia, pregnancy-induced hypertension,
      placental abruption, respiratory distress syndrome or intraventricular
      haemorrhage. Preterm labour was the only complication that occurred significantly
      more often in the triplet than in the twin gestation. CONCLUSIONS: We concluded
      that this information could be useful in counseling patients with respect to the
      anticipated perinatal outcome of triplet pregnancies.

PMID- 10965192
TI  - Methylenetetrahydrofolate reductase polymorphisms are not a risk factor for pre
      eclampsia/eclampsia in Australian women.
AB  - In European and Japanese but not in Australian, American, and South African
      women, the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism has
      been reported to be a genetic risk factor pre-eclampsia/eclampsia (PE/E). The
      recently described A1298C MTHFR gene polymorphism also results in reduced MTHFR
      enzyme activity, although to a lesser extent than the previously described C677T
      polymorphism. Heterozygotes for both polymorphisms are reported to have an even
      lower MTHFR enzymatic activity than seen in homozygotes for the C677T genotype.
      In this current study we determined the allele frequency of the A1298C MTHFR gene
      polymorphism in an Australian population and examined this polymorphism alone and
      in combination with the C677T MTHFR polymorphism for an association with PE/E.
      Neither the A1298C polymorphism alone nor a combination of both polymorphisms
      showed an association with PE/E in our population of Australian women.

PMID- 10965193
TI  - Prostacyclin deficiency and reduced fetoplacental blood flow in pregnancy-induced
      hypertension and preeclampsia.
AB  - BACKGROUND: Low endothelial generation of prostacyclin (PGI(2)) is a typical
      feature of pregnancy-induced hypertensive disorders. The aim of the current study
      was to establish whether changes in PGI(2) are accompanied by alterations in
      fetoplacental blood flow and to test the hypothesis that PGI(2) deficiency
      contributes to reduced fetoplacental perfusion in pregnancy-induced hypertension
      (PIH) and preeclampsia. METHODS: The study included 11 women with normal
      pregnancies, 12 with PIH/preeclampsia, and 7 with otherwise complicated
      pregnancies. Fetoplacental blood flow was assessed both by umbilical artery
      Doppler sonography measuring the resistance index (RI) and by means of neonatal
      birth weight. PGI(2) formation was measured in umbilical arteries prepared
      immediately after birth. PGI(2), RI and birth weight were correlated with and
      without correction for gestational age. Furthermore, data from patients with
      PIH/preeclampsia were compared with normal pregnancies as controls. RESULTS: A
      significant inverse correlation was found between umbilical PGI(2) formation and
      umbilical RI and between birth weight and RI, whereas PGI(2) and birth weight
      were directly related. Patients with PIH/preeclampsia showed reduced PGI(2)
      formation, markedly increased gestational age-corrected RI and significantly
      reduced percentile birth weight. CONCLUSIONS: These results provide evidence
      showing that PGI(2) is a relevant mediator of fetoplacental blood flow and
      suggest an important role of PGI(2) deficiency in PIH/preeclampsia.

PMID- 10965195
TI  - Lipid peroxidation in pregnancy with preeclampsia and diabetes.
AB  - We studied lipid peroxidation and vitamin E levels in 12 diabetic preeclamptic,
      13 nondiabetic preeclamptic, 8 gestational diabetic, 25 normotensive pregnant
      women, and 25 healthy nonpregnant women. A significant increase in malonaldehyde
      (MDA) levels was observed in preeclamptic and diabetic preeclamptic women as
      compared to normotensive pregnant and healthy controls (p<0.001). An increase in
      MDA levels was observed in gestational diabetics, but the difference was not
      statistically significant. Likewise, a significant fall in vitamin E levels was
      noted in preeclamptic and diabetic preeclamptic groups as compared to controls
      (p<0.001). Gestational diabetics had a slight decrease in vitamin E levels
      relative to controls. These findings suggest that lipid peroxidation plays a role
      in the pathogenesis of preeclampsia.

PMID- 10965194
TI  - Perinatal outcome of pregnancies complicated by diabetes and by maternal daily
      hyperglycemia not related to diabetes. A retrospective 10-year analysis.
AB  - We analyzed the perinatal outcome of 1,086 pregnancies classified according to
      the response to the 3-hour 100-gram glucose tolerance test and the diurnal
      glycemic profile into the Rudge groups corresponding to control pregnant women,
      class A gestational diabetic women, class A/B to FRH pregnant women and women
      with daily hyperglycemia. Despite treatment, the diabetic pregnant women and
      those with daily hyperglycemia presented higher mean blood glucose levels
      compared to controls (76.6+/-10.2 mg/dl). The pregnancies complicated by diabetes
      and by daily hyperglycemia were characterized by a high incidence of prematurity,
      macrosomia, large for gestational age newborn infants, malformation and fetal and
      neonatal death, with consequent perinatal mortality. The perinatal mortality of
      women with daily hyperglycemia was 10 times higher than that of the controls and
      was similar to that of the diabetic patients. These adverse perinatal results
      emphasize the need for the diagnosis and control of intrauterine hyperglycemia
      both in diabetic pregnant women and in women with an altered diurnal glycemic
      profile.

PMID- 10965196
TI  - Tubal ligation, hysterectomy and D&C: evidence from the Melbourne Women's Midlife
      Health Project.
AB  - The question of whether tubal ligation (TL) is associated with increased risk of
      hysterectomy or dilatation and curettage (D&C) is examined using data from a
      population-based study. Retrospective information on TL, D&C and hysterectomy was
      gathered from 1,810 Australian-born women aged 45-55 who were randomly selected
      from the population of Melbourne, Australia. Odds ratios for the outcomes were
      adjusted via logistic regression for age, years of education, smoking status,
      alcohol consumption, history of premenopausal complaints, number of lost
      pregnancies, and whether women have discussed menstruation or menopause with
      their doctor. With these variables taken into account, TL does not emerge as a
      risk factor for hysterectomy. Though there was a significant association between
      TL and the probability of ever experiencing a D&C, related extraneous variables
      which appear to link these events are identified.

PMID- 10965197
TI  - Serum group II phospholipase A(2) levels during menstrual cycle and pregnancy.
AB  - The purpose of this study was to evaluate the circulating group II phospholipase
      A(2) (PLA(2)-II) levels during normal menstrual cycle and to assess alterations
      in maternal circulating PLA(2)-II concentrations during pregnancy and at
      puerperium. Circulating serum PLA(2)-II concentrations were compared between 38
      nonpregnant women with normal menstrual cycle (15 at menstrual phase, 11 at
      follicular phase, and 12 at luteal phase), 61 normal pregnant women (13 in the
      first trimester, 12 in the second trimester, and 36 in the third trimester), and
      14 normal postpartum women at 5th puerperal day. Serum PLA(2)-II concentrations
      were also measured in 11 patients with threatened premature labor. Maternal and
      fetal serum PLA(2)-II levels before and after delivery were made to determine
      differences in 11 neonates delivered vaginally and 11 neonates delivered by
      elective cesarean section. Serum PLA(2)-II level was measured with an
      immunoradiometric assay. Serum PLA(2)-II concentrations at luteal phase were
      significantly lower than those at menstrual or follicular phase (p< 0.05). There
      was no significant difference for PLA(2)-II levels between first trimester and
      menstrual phase or follicular phase. There were no significant differences among
      three trimesters during pregnancy. There was no significant difference in serum
      PLA(2)-II levels between normal pregnant women and patients with threatened
      premature labor. Labor stress did not affect both maternal and fetal serum PLA(2)
      II concentrations. There was also no significant difference for circulating
      PLA(2)-II levels between maternal and fetal serum. Interestingly, serum PLA(2)-II
      concentrations in postpartum women were significantly higher than those in normal
      pregnant women (p<0.05). These results suggest that a regulatory mechanism of
      PLA(2)-II may exist during the normal menstrual cycle and at puerperium.

PMID- 10965198
TI  - Adjuvant chemotherapy including cisplatin in endometrial carcinoma.
AB  - To determine the outcome of patients with endometrial endometrioid adenocarcinoma
      following adjuvant chemotherapy, CAP (cyclophosphamide, pirarubicin and
      cisplatin) and EP (etoposide and cisplatin) were assigned at random to patients
      with Ic or more advanced stage carcinoma, and their efficacy was compared. These
      patients were treated by the Tokai Endometrial Cancer Study Group (Nagoya
      University and related institutions) between January 1992 and June 1996. The 5
      year survival rate was 88.4% in the CAP group and 95.1% in the EP group; the
      difference between the two groups was not significant (p = 0.3496). The disease
      free survival rate was 80. 3% in the CAP group and 84.8% in the EP group
      (nonsignificant: p = 0. 4533). However, the 5-year disease-free survival rates
      were 95.1 and 71.0% in patients with preoperative CA125 levels <35 and > or =35
      IU/ml, and there was a significant difference in disease-free survival curves
      (p<0.05). A significant difference was also observed in disease-free survival
      curves between patients with and without pelvic lymph node metastasis (5- year
      disease-free survival rate: 68.8 and 88.2% in patients with and without pelvic
      lymph node metastasis, respectively, p<0.05). Multivariate analysis of disease-
      free survival showed that the preoperative CA125 level, and pelvic lymph node
      metastasis were significant risk factors for recurrence. In conclusion, the EP
      chemotherapy had no significant advantage in terms of survival and disease-free
      survival compared to CAP, although these rates were superior in the EP group
      compared to the CAP group.

PMID- 10965199
TI  - New cervicoscopy with toluidine blue staining for superficial cervical invasion
      by endometrial carcinoma.
AB  - We developed a method of endocervical staining with toluidine blue solution
      during cervicoscopy that clearly discriminates between the endocervical region
      and the endometrium and allows easy detection of superficial cervical invasion by
      endometrial carcinoma. Toluidine blue staining cervicoscopy was used for
      preoperative histological diagnosis in 10 cases of endometrial carcinoma. The
      staining permitted a correct diagnosis in 3 cases in which conventional
      diagnostic methods were practically useless. Endocervical staining with toluidine
      blue is highly useful for diagnosis of superficial cervical invasion by
      endometrial carcinoma.

PMID- 10965200
TI  - Endometrial metastasis from breast cancer in a patient receiving tamoxifen
      therapy.
AB  - Tamoxifen (TAM) is known to be associated with several types of endometrial
      pathologies, e.g. hyperplasias, polyps and endometrial carcinomas, sometimes of
      special histologic type. Here we report a rare case of endometrial metastasis
      from a breast carcinoma (ductal carcinoma) discovered during TAM therapy. This
      occurrence does not suggest that TAM treatment causes endometrial metastases of
      breast cancer. However, clinicians should be aware of this possibility and
      provide patients receiving TAM therapy with close gynecologic follow-up using
      liberal indications for endometrial biopsies.

PMID- 10965201
TI  - A 22-week cervical pregnancy.
AB  - We report on a cervical pregnancy at advanced gestational age. Misdiagnosis
      allowed pregnancy to proceed until the 22nd week of gestation and made its
      management more complicated. An abdominal hysterectomy with preservation of the
      adnexa was performed.

PMID- 10965202
TI  - A severe case of myasthenia gravis during pregnancy.
AB  - Myasthenia gravis is characterised by muscle weakness and fatigability,
      particularly of the facial and extremity muscles, deteriorating during the day.
      During pregnancy, myasthenia gravis is rare and the course of illness is
      unpredictable. The present case illustrates that first diagnosed during
      pregnancy, recurrent exacerbations can appear and lead to life-threatening
      situations.

PMID- 10965203
TI  - Timing of sonohysterography in menstruating women.

PMID- 10965204
TI  - Pubertal growth of the short normal girl.
AB  - OBJECTIVES: To determine the timing, magnitude and duration of the pubertal spurt
      for short normal and average height girls, to compare these with Tanner's
      standard and to investigate predictors of pubertal growth. METHODS: The growth of
      46 short normal and 55 control girls, identified at school entry, was monitored
      throughout puberty. Height and weight were measured at 6-month intervals from
      which body mass index (BMI) was derived. Annual velocities were calculated and
      used to estimate the age and magnitude of peak height velocity (PHV). Age of
      menarche was recorded to the nearest month. Parents provided information on the
      child's medical and social history. RESULTS: The mean age at PHV, the magnitude
      of PHV and age at menarche were similar for both groups and close to Tanner's
      50th centile values. Pre-pubertal BMI predicted age at menarche for short and
      control girls, accounting for 17% of the variance. There was a tendency for early
      maturing girls of average stature to have greater PHV. However, this relationship
      was not observed in short girls, nor did any other variable, genetic or
      environmental, predict the timing or magnitude of their pubertal spurt.
      CONCLUSIONS: Delayed puberty in short normal girls is unlikely and their growth
      during puberty is comparable to girls of average height. The pubertal variables
      measured remain close to Tanner's original standards for both groups, suggesting
      the lack of a secular trend towards earlier puberty in girls. The onset of
      menstruation is influenced by pre-pubertal BMI. However, the clinician should be
      aware that short normal girls have normal pubertal growth and that no genetic or
      environmental variable can predict the timing or magnitude of their growth spurt.

PMID- 10965205
TI  - Leptin levels in menopause: effect of estrogen replacement therapy.
AB  - To evaluate the effect of menopause and estrogen replacement therapy on leptin
      levels, 17 white postmenopausal women were recruited for the study. After an
      overnight fasting, blood samples were collected for LH, FSH, estradiol,
      testosterone, androstenedione, DHEA sulfate, insulin and leptin assays. Body mass
      index (BMI) and the waist-to-hip ratio were also evaluated. Patients were
      reanalyzed after a 12-week administration of transdermal estrogen patches
      delivering 50 microg 17beta-estradiol. The results were compared to those
      obtained from a group of 11 female volunteers in reproductive age, in whom basal
      blood was sampled during the early follicular phase of their cycle. Patients were
      divided into lean and obese according to their BMI. Obese postmenopausal women
      showed lower leptin levels when compared to premenopausal counterparts (25.1 +/-
      5.9 vs. 37 +/- 11.3; p < 0.05), whereas no significant differences were found
      between the lean groups (14.5 +/- 3.8 vs. 14.4 +/- 4.9). Estrogen administration
      did not significantly change serum leptin concentrations in hypoestrogenized
      women (obese: 25.1 +/- 5.9 vs. 28. 6 +/- 9.2; lean: 14.4 +/- 4.9 vs. 17.6 +/-
      7.2). A positive linear correlation was found between leptin plasma levels and
      BMI only in obese patients (r = 0.58; p < 0.01) both before and after estrogen
      treatment. Menopause is characterized by a decreased expression of the obese
      gene, even if estrogens do not seem to represent a main causal factor.

PMID- 10965206
TI  - Comparison between low- and standard-dose ACTH tests in premature infants at risk
      for chronic lung disease.
AB  - In order to find a sensitive method to evaluate adrenocortical function in
      premature infants, we compared low- (0.5 microg/1.73 m(2)) and standard-dose (250
      microg/1.73 m(2)) adrenocorticotropin tests (LD- and SD-ACTH) in 12 very-low
      birth-weight infants before and 2 days after the end of dexamethasone therapy
      (duration 9-14 days) for chronic lung disease. Basal serum cortisol levels were
      inappropriately low in several infants already before dexamethasone therapy
      (median 190, range 60-357 nmol/l). The 95% confidence intervals of mean serum
      cortisol levels at 20 min were equal in LD- and SD-ACTH, while at 60 min, the low
      dose gave a clearly lower response than the standard-dose test. The LD-ACTH can
      be used in premature infants as in older children and adults, but the criteria
      for adrenocortical insufficiency need to be defined.

PMID- 10965207
TI  - Relation of leptin and tumor necrosis factor alpha to body weight changes in
      patients with pulmonary tuberculosis.
AB  - In this study we investigated whether leptin and TNFalpha levels change with
      improvement in body weight with antituberculotic therapy in active tuberculosis
      patients. 30 patients (8 females and 22 males) with active pulmonary tuberculosis
      formed the patient group, and 25 sex- and age-matched healthy subjects (8 females
      and 17 males) served as the control group. Body weight, body mass index (BMI) and
      serum leptin and plasma TNFalpha levels are measured before and in the sixth
      month of therapy in all patients. Before the initiation of therapy, BMI of the
      patients was significantly lower than BMI of the controls (20.2 +/- 1.6 vs. 25.2
      +/- 2.7 kg/m(2), respectively; p < 0.05). After treatment, BMI of the patients
      increased significantly to 21.4 +/- 1.9 kg/m(2) (p < 0.05), but was still lower
      than that of the controls (p < 0.05). Pretreatment serum leptin (4.5 +/- 0.9 vs.
      2.1 +/- 0.2 ng/ml, respectively; p < 0.05) and plasma TNFalpha (27.9 +/- 3.4 vs.
      23.9 +/- 3.0 pg/ml, respectively; p < 0.05) levels of the patients were
      significantly higher than those of the controls. After treatment, serum leptin
      levels increased to 6.7 +/- 2.2 ng/ml, but this rise was not statistically
      significant (p > 0.05). Treatment did not result in any significant change in
      TNFalpha levels, either. Delta leptin was highly related to Delta BMI in patients
      with tuberculosis (r = 0.68, p = 0.02). In the pretreatment period, there was a
      significant correlation between leptin and TNFalpha levels in the whole patient
      group (r = 0.78, p < 0.001), and in female (r = 0.74, p < 0.001) and male
      patients separately (r = 0.74, p = 0.035). In conclusion, leptin and TNFalpha may
      be responsible for the weight loss in pulmonary tuberculosis patients, but their
      levels do not change with improvement in body weight with antituberculotic
      treatment.

PMID- 10965208
TI  - Neonatal thyroid-stimulating hormone screening as an indirect method for the
      assessment of iodine deficiency in Estonia.
AB  - According to neonatal thyroid screening the incidence of congenital
      hypothyroidism in Estonia is 1:2,860. Transient hyperthyrotropinemia with a
      raised thyroid-stimulating hormone level of 5 microU/ml occurred in 17.7% of
      infants and was not associated with low birth weight, small birth length, low
      gestational age or congenital anomalies. Based on WHO criteria (WHO/UNICEF, 1994)
      it corresponds to mild iodine deficiency in Estonia (3% or less is in iodine
      sufficient areas). This is in agreement with the previously reported median
      urinary iodine content of 65 microg/l in children. The frequency of infants with
      TSH >5 microU/ml was 16.4, 21 and 17. 2% in three regions (north, central and
      south) of Estonia, respectively, indicating mild to moderate iodine deficiency.
      These findings show the possibility of using the results of newborn screening for
      congenital hypothyroidism to assess the severity of iodine deficiency in Estonia.
      The introduction of universal iodine prophylaxis is recommended.

PMID- 10965209
TI  - Gulliver G-100 - A new device to evaluate daily growth measurement in comparison
      with Harpenden stadiometer.
AB  - To reduce the time to monitor success of growth hormone therapy, Gulliver G-100
      (G-100), a new portable height measurement device based on ultrasound technology,
      was developed and compared with a conventional determination system, the
      Harpenden stadiometer (HS). In addition, growth of 12 children was monitored at
      home twice per day 3 months before and 3 months during GH therapy. Mean body
      height of 101 children was 144.67 cm using G-100 compared to 145.16 cm using HS.
      The coefficient of variability of 3 measurements from each patient was 0.29 and
      0.18 using G-100 or HS, respectively. Statistic analysis of these data revealed
      no significant difference between G- 100 or HS. Statistical analysis of short
      time growth of 12 patients revealed an increase of growth velocity for 8 patients
      (p < 0.01) after 3 months. Calculated growth velocity using data revealed from
      short-time growth analysis with G-100 and using long-term growth analysis with HS
      did not show any significant difference. Our data reveal that G-100 is able to
      produce accurate results in height measurement comparable to the HS. Using G-100,
      the patient can be classified as a 'responder' of GH therapy already after 3
      months.

PMID- 10965210
TI  - Tubercular involvement of the thyroid gland: a report of two cases.
AB  - Thyroid tuberculosis is rare. In the last decade, however, the incidence of
      extrapulmonary forms of tuberculosis has increased. We report on 2 cases of
      thyroid tuberculosis. In case 1, a tubercular abscess mimicking acute thyroiditis
      was found which was correctly diagnosed by fine-needle aspiration biopsy (FNAb).
      No evidence of active disease was noticed. Pleural thickening on chest X-ray was
      the only sign compatible with a previous infection. In case 2, tubercular
      thyroiditis with lymph node enlargement was also diagnosed by FNAb in a
      reevaluation setting. In both cases treatment with antitubercular drugs resulted
      in complete recovery. Thyroid tuberculosis should be kept in mind in the
      differential diagnosis of thyroid nodules, notably in patients with a history of
      tuberculous disease. FNAb represents the main approach to making the diagnosis.

PMID- 10965211
TI  - Gastrectomy and osteomalacia: an association not to be forgotten.
AB  - Metabolic bone disease due to calcium and vitamin D malabsorption is a well
      defined consequence of gastrectomy and to a lesser extent of pancreatic
      insufficiency. The diversity of its presentation, however, can be misleading,
      resulting in delayed diagnosis or a thorough investigation for possible
      underlying neoplasias being undertaken. We describe the case of a man with
      partial gastrectomy and pancreatectomy with osteomalacia and secondary
      hyperparathyroidism.

PMID- 10965212
TI  - Aldosterone synthase deficiency type I: hormonal and genetic analyses of two
      cases.
AB  - Two female infants with clinical and biochemical findings of mineralocorticoid
      deficiency are presented. Both cases were diagnosed with aldosterone synthase
      type-I deficiency by multisteroid analysis. Two different mutations were located
      in the CYP11B2 gene: two homozygous amino acid substitutions (E188D and V386A) in
      case 1, and one heterozygous substitution (L324Q) and one heterozygous stop
      mutation (Y265X) in case 2.

PMID- 10965213
TI  - Effect of growth hormone and oxandrolone treatment on glucose metabolism in
      Turner syndrome. A longitudinal study.
AB  - In 18 girls with Turner syndrome, glucose tolerance was studied before treatment
      and after 6 and 24 months of growth-promoting treatment with recombinant human
      growth hormone (24 IU/m(2)/week; 8 mg/m(2)/week) and oxandrolone (0.06
      mg/kg/day), as well as after termination of the treatment. One girl developed an
      overt non-ketotic diabetes mellitus 50 months after termination of treatment. The
      results of the remaining 17 girls in whom the effect of treatment on glucose
      metabolism was reversible are presented as a group. Their median age at the
      beginning of the treatment was 10.4 years (range 6.9-15.9), and 15.0 years (range
      12.1-19.9) at the final assessment. There was a moderate, but not significant
      rise in fasting glucose throughout the course of the longitudinal study. At oral
      glucose tolerance testing (oGTT), the area under the curve for glucose rose
      significantly (p = 0.013) during the period of treatment and returned to the
      basic value thereafter. Fasting insulin and especially the integrated insulin
      values (AUCi; area under the curve for insulin) during oGTT increased
      continuously during treatment, declined after termination of treatment but were
      still significantly (p = 0.04) higher than before treatment. Considering the fact
      that in untreated girls with Turner syndrome the fasting insulin and the AUCi
      increase with age, one can conclude that the insulinaemia returned to age
      specific norm after termination of treatment. Thus the effect of a combined
      growth hormone and oxandrolone growth-promoting treatment on glucose metabolism
      was fully reversible in these 17 girls with Turner syndrome.

PMID- 10965214
TI  - Androgen insensitivity syndrome (AIS): emotional reactions of parents and adult
      patients to the clinical diagnosis of AIS and its confirmation by androgen
      receptor gene mutation analysis.
AB  - The emotional reactions of parents and adult patients on disclosure of the
      clinical diagnosis of androgen insensitivity syndrome (AIS) and its later
      confirmation by gene mutation analysis were assessed. A semistructured interview
      and three questionnaires were used. Parents came from 18 different families with
      a total of 20 children (15 complete AIS, 5 partial AIS), 19 raised as girls, 1 as
      a boy. Ten adult women with complete AIS came from six families. The short-term
      reaction upon the clinical diagnosis was in the majority of both parents and
      adult patients associated with shock, grief, anger, and shame and in the mothers
      and adult patients with guilt. Emotional reactions were more long-lasting in
      mothers and adult patients than in fathers. The confirmation by DNA analysis did
      not alter the actual feelings of both parents. Adolescents with AIS should be
      informed completely - but in a step-by-step way - about their condition, since
      adult patients indicated that they had suffered from being not at all or
      misinformed about AIS in their adolescence.

PMID- 10965215
TI  - Macroprolactinemia in childhood and adolescence: a cause of asymptomatic
      hyperprolactinemia.
AB  - Asymptomatic hyperprolactinemias associated with altered proportions of molecular
      forms of circulating prolactin (PRL) have been reported in adults. The scarce
      references available in children and adolescents prompted us to report our
      experience in the evaluation and follow-up of patients with macroprolactinemia.
      We studied 5 patients (1 male and 4 females) aged 11.6-18 years with incidentally
      discovered asymptomatic hyperprolactinemia. Patients underwent repeated
      evaluations for a period of 3 months to 8 years, and their PRL levels remained
      elevated (34.4-516 ng/ml). Structural variants of PRL >/=45 kD ranged between
      58.9 and 78.6%. Chromatographic profiles showed increases in Big Big PRL in the 5
      cases, ranging between 40 and 72% (normal: 9-21%), and in Big PRL in 3 cases,
      ranging between 30.0 and 32.6% (normal: 5-25%). Little PRL was decreased in all
      cases, ranging between 20.6 and 41.1% (normal: 50-90%). In conclusion, upon
      detection of hyperprolactinemia with no clinical manifestations and no alteration
      of the remaining endocrine functions, macroprolactinemia should be considered as
      a possible diagnosis. The confirmed absence of functional alterations during the
      follow-up would favor a no-treatment approach and at the same time avoid
      repeating imaging studies.

PMID- 10965216
TI  - Augmentative effect of polyethylene glycol, polyvinyl alcohol and dextran on
      thyroid-stimulating antibody stimulated cAMP production in FRTL-5 cells and CHO
      cells expressing human TSH receptor.
AB  - Previously we reported the augmentative effect of nonionic hydrophilic polymers
      such as polyethylene glycol (PEG), polyvinyl alcohol (PVA) and dextran on thyroid
      stimulating antibody (TSAb) activity in porcine thyroid cell assays. We examined
      whether a similar phenomenon occurs in FRTL-5 thyroid cells and CHO cells
      expressing the human (h) TSH receptor (CHO-hTSHR cells). As with porcine thyroid
      cells, PEG 22.5% precipitated crude IgG from serum of patients with Graves'
      disease, significantly increased cAMP production as compared with PEG 12.5%
      precipitated crude IgG in both FRTL-5 cells and CHO-hTSHR cells. PEG 5% augmented
      purified-TSAb-IgG-stimulated cAMP production in both cell assays. TSAb activities
      and positivity by the direct assay using whole serum (0.05 ml) in the presence of
      5% PEG in untreated Graves' patients were significantly increased as compared
      with the absence of 5% PEG. The augmentative effects of PVA 10% or dextran T-70
      10% on TSAb-IgG-stimulated cAMP production were also observed in both cell
      assays. PVA 10% did not augment TSH-stimulated cAMP production in spite of weak
      augmentation by dextran 10% in both cell assays. Lack of the augmentative effects
      of PEG 5%, PVA 10% and dextran 10% on cAMP produced by GTPgammaS, forskolin and
      pituitary adenylate cyclase activating polypeptide was observed in both cell
      assays. The augmentative effects of these polymers in both cell assays similar to
      porcine thyroid cells suggest that there is no apparent species specificity among
      human, porcine and rat thyroid cells as far as TSH receptor linked cAMP
      production in cell membranes existed.

PMID- 10965217
TI  - Clinical, endocrine, and molecular genetic findings in patients with 17beta
      hydroxysteroid dehydrogenase deficiency.
AB  - Mutations in the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 3 gene are
      associated with the clinical findings of 17beta-HSD deficiency. We investigated 5
      patients of German descent with 46,XY karyotype and predominantly female
      phenotype. Androstenedione (A) and testosterone (T) levels in serum were
      determined before and after stimulation with human chorionic gonadotropin. DNA
      analysis of the whole coding region of the 17beta-HSD type 3 gene was performed
      by PCR, single-strand conformation analysis, and direct sequencing. In all
      patients we found highly variable A and T levels before and after stimulation.
      However, the A-to-T ratio was abnormal in all cases suggestive of 17beta-HSD
      deficiency. Molecular genetic analysis revealed mutations in all patients. We
      conclude that A and T levels may be highly variable in patients with 17beta-HSD
      deficiency. Molecular genetic analysis of the 17beta-HSD gene may support the
      diagnosis of this disorder.

PMID- 10965218
TI  - Plasma leptin concentrations in phenylketonuric patients.
AB  - High levels of phenylalanine (Phe) in blood have been shown to reduce dopamine
      (DA) and noradrenaline (NA) production. Leptin levels rise with increasing
      adiposity in rodents and humans acting as a negative feedback adipostatic signal
      to brain centers. The aim of this study was to evaluate leptin plasma levels in
      phenylketonuria (PKU) patients adhering to their special diet and in those on a
      'loose diet'. Forty-nine patients with classical PKU were divided into two
      groups. Those in group A (n = 21) adhered very strictly to their diet (Phe: 0.15
      +/- 0.04 mmol/l) and those in group B (n = 28) were on a 'loose diet' (Phe: 0.8
      +/- 0.04 mmol/l). Thirty healthy children of comparable age served as controls.
      Both patients and controls were in pubertal stage 0 (Tanner). BMI (kg/m(2)) was
      evaluated in all the members of the groups. Their daily nutrients were calculated
      with a 7-day dietary protocol. Leptin was evaluated by RIA, and Phe and Tyrosine
      with an amino acid autoanalyser. Adrenaline (A), NA and DA were measured by an
      HPLC method. Plasma leptin in group B patients (28.4 +/- 2.0 ng/ml) was
      significantly increased as compared to group A patients (16.8 +/- 2. 6 ng/ml) and
      controls (17.8 +/- 3.0 ng/ml; p < 0.001). Plasma DA, A, and NA in group B was
      lower than in group A and controls. Additionally, leptin negatively correlated
      with A and DA, whereas Phe positively correlated with the hormone in all groups.
      Leptin, also, correlated with BMI only in group A and controls. Additionally, the
      hormone negatively correlated with the total energy intake only in group A (r = 
      0.43, p < 0.01) and in controls (r = -0.040, p < 0.01). It is suggested that the
      disregulation of the neuroendocrine system as well as the high Phe blood levels
      might play an important role in the increased leptin concentrations in PKU
      patients on a 'loose diet'.

PMID- 10965219
TI  - Tamoxifen inhibits lipoprotein activity: in vivo and in vitro studies.
AB  - Tamoxifen, a nonsteroidal antiestrogenic antitumor agent, has weak estrogen-like
      effects on lipid metabolism, however, the mechanism remains unknown. We
      previously reported that tamoxifen decreases the activity of lipoprotein lipase
      (LPL), a key enzyme in triglyceride metabolism, in patients with breast cancer.
      This study evaluated the effect of tamoxifen on LPL activity in vitro and in
      vivo. In experiment 1, total cholesterol, triglyceride, adipose tissue weight,
      and LPL activity of post-heparin plasma were measured in ovariectomized female
      rats with and without tamoxifen treatment. In experiment 2, purified very-low
      density lipoprotein (VLDL) and purified LPL were incubated with and without
      tamoxifen or estrogen, and the triglycerides in VLDL were measured using an
      enzymatic method. In experiment 1, total cholesterol and adipose tissue weight
      decreased significantly in tamoxifen-treated rats (p < 0.001 and p < 0.01,
      respectively). Triglyceride measurements were not significantly different between
      the two groups, however, the LPL activity was lower in tamoxifen-treated rats (p
      < 0.005). In experiment 2, triglycerides in VLDL were significantly higher after
      VLDL and LPL were incubated with tamoxifen and estrogen (p < 0.005). We concluded
      that tamoxifen inhibits the hydrolytic activity of LPL in vivo and in vitro. This
      mechanism may explain the elevated serum triglyceride levels in some patients
      treated with tamoxifen.

PMID- 10965220
TI  - N-glycosylated variants of growth hormone in human pituitary extracts.
AB  - This study was designed to investigate the existence, in human pituitary
      extracts, of growth hormone (GH) variants not encoded by the hGH-N gene. Using
      anion exchange-fast protein liquid chromatography followed by SDS-PAGE, we
      isolated several basic forms of pituitary GH. Incubation of these basic forms
      with endoglycosidase F/N-glycosidase F revealed that two of them (about 34 and 12
      kD) were N-glycosylated. In contrast, no changes were found when samples were
      incubated with the O-linked glycosylation-specific O-glycosidase. Since the GH-N
      molecule lacks consensus sequences for N-linked glycosylation, our findings
      suggest that GH genes other than hGH-N are expressed in the human pituitary
      gland.

PMID- 10965221
TI  - Control of catecholamine release and blood pressure with octreotide in a patient
      with pheochromocytoma: a case report with in vitro studies.
AB  - A 65-year-old male patient with pheochromocytoma, whose hypertensive episodes
      were uncontrolled using conventional therapy, was successfully treated with
      octreotide (SMS 201-995). The serum catecholamine level and the urinary excretion
      of catecholamines decreased after 300 microgram/day of octreotide was
      administered. To clarify the mechanisms of octreotide that lower catecholamine
      released from a tumor, we studied the in vitro effects of octreotide on membrane
      potentials and voltage-dependent Ca(2+) channel (VDCC) current using the whole
      cell patch-clamp technique in single pheochromocytoma cells dispersed after tumor
      resection. The action potentials were reversibly inhibited with 10 microM
      octreotide. In addition, the VDCC current evoked by depolarized pulses from the
      holding potential of -60 mV was inhibited with 10 microM octreotide. Octreotide
      is useful for controlling blood pressure before surgery in some patients with
      uncontrolled hypertension caused by a pheochromocytoma.

PMID- 10965222
TI  - Toxicity, uptake kinetics and efficacy of new transfection reagents: increase of
      oligonucleotide uptake.
AB  - Human arterial smooth muscle cell (haSMC) proliferation is stimulated by platelet
      derived growth factor (PDGF) release of human arterial endothelial cells (haEC)
      whereas transforming growth factor-beta(1) (TGF-beta(1)) secretion by haSMC
      promotes extracellular matrix formation. Inhibitory concepts with antisense
      oligonucleotides (ASO) against those growth factors might be promising,
      requiring, however, sufficient transfection efficacy. Thus, toxicity and efficacy
      of new transfection reagents were examined. MTT tests showed that high doses >1.6
      microg/ml of the liposome Cytofectin GSV((R)) (CF) and the dendrimer SuperFect
      (SF) reduced mitochondrial activity of haEC after > or =4 h transfection whereas
      viability of haSMC was not influenced. DAC-30((R)) showed significant toxic
      effects on haEC and haSMC at each dose after > or =4 h and Lipofectin((R)) (LF)
      caused complete detachment of haEC and haSMC in medium containing 10% serum.
      Uptake studies demonstrated that 'naked' ASO were not incorporated
      intracellularly whereas transfection within CF or SF resulted in a strong
      cytoplasmic and nuclear labeling after 2-5 h. With DAC-30, only a slight
      cytoplasmic fluorescence was found. SF caused an unexpected stimulation of
      endothelial PDGF-AB synthesis. Thus, CF was favored for inhibition studies.
      ELISA, Western and Northern blotting showed a significant inhibition of
      endothelial PDGF-B and smooth muscle TGF-beta(1) mRNA expression and synthesis
      after transfection for 3-5 h using 0.1-1.0 microM ASO versus control
      oligonucleotides. We conclude that Cytofectin GSV is superior to the other
      transfection reagents, predominantly at haEC, showing an improved efficacy and
      less toxicity than the classical liposome Lipofectin. Cytofectin GSV might offer
      a promising tool for antisense strategies in the treatment of vascular disorders.

PMID- 10965224
TI  - Functional characteristics of optimized arterial tree models perfusing volumes of
      different thickness and shape.
AB  - The relationship between the 'shape of an organ' and the 'cost of blood
      transport' to perfuse its tissue was evaluated on the basis of optimized arterial
      model trees simulated to perfuse square-based 100-cm(3) volumes of different
      shape ('flat' versus 'thick' as defined by the ratio of thickness to side-length
      h/s < or =1). Specifically, the effects of 'shape' on tree structure, blood
      transport, and on hemodynamic characteristics were investigated. Branching models
      of arterial trees were generated by constrained constructive optimization (CCO),
      based on an identical set of model parameters. All model trees were geometrically
      and topologically optimized for intravascular volume. Tree structures achieved
      tremendous savings of blood (transport medium) in comparison to a system of
      separate tubes. Thickening the perfusion volume (increasing h/s) resulted in a
      significant decrease of mean transport length, deposition time, and intravascular
      total volume in the tree. 'Thick' perfusion volumes induced CCO trees to branch
      more symmetrically into a number of equivalent subtrees repetitiously splitting
      into smaller ones; 'flat' structures were dominated throughout by a few
      asymmetrically branching major vessels. In summary, we conclude from systematic
      variation of shape that thicker perfusion volumes (h/s >0.1) facilitate efficient
      delivery of blood in comparison to large amounts of 'dead volume' to be carried
      over long distances in very thin pieces of tissue.

PMID- 10965223
TI  - Cyclic nucleotide hydrolysis in bovine aortic endothelial cells in culture:
      differential regulation in cobblestone and spindle phenotypes.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) were investigated in cultured bovine
      aortic endothelial cells having two phenotypes, cobblestone and spindle,
      representing, respectively, the resting and angiogenic phenotypes in vivo.
      Spindle cell homogenates displayed higher hydrolytic activities towards cAMP
      (52%) and cGMP (10-fold). These increases were due to: (1) increased number of
      spindle PDE isozymes in the cytosolic fraction (for cAMP: PDE1, PDE2, PDE3 and
      PDE4 compared to PDE2 and PDE4 in cobblestone; for cGMP: PDE2 and PDE5 compared
      to PDE2 in cobblestone); (2) increased spindle-specific activities of cytosolic
      and particulate PDE2, cytosolic PDE3 and particulate PDE4. These changes were
      associated with an increase in spindle transcripts: 7.5 kb PDE3A (6-fold) and 7.0
      kb PDE4D (3-fold). Moreover, cAMP hydrolysis in the two phenotypes was
      differently regulated by 5 microM cGMP: 60% increase in total cAMP-PDE activity
      in cobblestone homogenate related to PDE2 stimulation; 30% decrease in spindle
      homogenate related to PDE3 inhibition. This underlines the roles played by PDE2,
      PDE3 and PDE5 in the cross-talk involving the two cyclic nucleotides. These
      changes in PDE isozyme expression along with the cross-talk between cAMP and cGMP
      may well modulate NO production and consequently might participate in
      angiogenesis, making PDEs potential targets to modulate angiogenesis.

PMID- 10965225
TI  - The interaction between oxidised chylomicron remnants and the aorta of rats fed a
      normocholesterolaemic or hypercholesterolaemic diet.
AB  - The effects of oxidised chylomicron remnants on endothelium-dependent relaxation
      and lipoprotein uptake were studied in both the normocholesterolaemic and
      hypercholesterolaemic rat aorta in vitro. Incubation of aortic rings taken from
      normocholesterolaemic animals with oxidised (by treatment with copper sulphate)
      chylomicron remnant particles resulted in a reduction in both vessel sensitivity
      and maximum percent relaxation in response to carbachol (CCh) and ATP, without
      affecting responses to A23187 and S-nitroso-N-acetylpenicillamine (SNAP). Studies
      comparing control vessels and those taken from fat-fed rats confirmed that
      hypercholesterolaemia significantly decreased relaxations in response to CCh and
      potentiated contractions in response to phenylephrine (PE) via a nitric oxide
      (NO)-dependent mechanism. Perfusion of the aorta of these hypercholesterolaemic
      rats for 2 h with (125)I-labelled oxidised chylomicron remnants showed that
      significantly greater amounts of lipoprotein became associated with the artery
      wall, as compared to control normocholesterolaemic animals. However, there was no
      significant difference in the uptake of native chylomicron remnant particles
      between control and hypercholesterolaemic vessels. Taken together, the findings
      of this study suggest that incorporation of lipoproteins of dietary origin into
      the arterial wall may contribute to endothelial dysfunction and that their
      contribution may be enhanced by hypercholesterolaemia. These data also support
      the putative involvement of oxidative modification in the atherosclerotic
      process, although the presence of oxidised chylomicron remnants in vivo and their
      role in atherogenesis remains to be established.

PMID- 10965227
TI  - The fractal nature of myocardial blood flow emerges from a whole-organ model of
      arterial network.
AB  - Mammalian hearts exhibit a heterogeneous spatial distribution of blood flows, but
      flows in near-neighbor regions correlate strongly. Also, tracer (15)O-water
      washout after injection into the inflow shows a straight log-log relationship
      between outflow concentration and time. To uncover the role of the arterial
      network in governing these phenomena, morphometric data were used to construct a
      mathematical model of the coronary arterial network of the pig heart. The model
      arterial network, built in a simplified three-dimensional representation of
      tissue geometry, satisfies the statistical morphometric data on segment lengths,
      diameters and connectivities reported for real arterial networks. The model uses
      an avoidance algorithm to position successive vascular segments in the network.
      Assuming flows through the network to be steady, the calculated regional flow
      distributions showed (1) the degree of heterogeneity observed in normal hearts;
      (2) spatial self-similarity in local flows; (3) fractal spatial correlations, all
      with the same fractal dimension found in animal studies; (4) pressure
      distributions along the model arterial network comparable to those observed in
      nature, with maximal resistances in small vessels. In addition, the washout of
      intravascular tracer showed tails with power law slopes that fitted h(t) = at(
      alpha-1) with the exponents alpha = 2 for the reconstructed networks compared
      with those from experimental outflow concentration-time curves with alpha = 2.1+/
      0.3. Thus, we concluded that the fractal nature of spatial flow distribution in
      the heart, and of temporal intravascular washout, are explicable in terms of the
      morphometry of the coronary network.

PMID- 10965226
TI  - Mg(2+)-induced vasodilation in human forearm vasculature is inhibited by N(G)
      monomethyl-L-arginine but not by indometacin.
AB  - We have investigated the mechanism of the vasodilator action of Mg(2+) in human
      forearm resistance vasculature. Venous occlusion plethysmography was used to
      measure vasodilator responses to Mg(2+) infused via the brachial artery in
      healthy men, and to determine effects on Mg(2+) responses of indometacin (an
      inhibitor of cyclo-oxygenase) and of N(G)-monomethyl-L-arginine (L-NMMA, an
      inhibitor of the L-arginine/nitric oxide, L-arg/NO, pathway). Magnesium sulphate
      infusion (0.05, 0.1, 0.2 mmol x min(-1)) increased plasma Mg(2+) concentration to
      1.57+/-0.16 mmol x l(-1) in venous blood from the infused arm at the highest
      dose. There was a dose-related increase in forearm blood flow in the infused arm
      to a maximum of 6.37+/-1.37 ml x min(-1) x dl forearm(-1) at the highest dose
      corresponding to an increase of 159+/-25% in blood flow relative to the non
      infused arm. There was no tachyphylaxis during a second infusion following a 21
      min recovery period. Indometacin had no effect on vasodilator responses to
      Mg(2+), whereas L-NMMA inhibited Mg(2+) responses (area under the dose-response
      curve) by 43+/-6% (p = 0.0003 by repeated-measures ANOVA). Therefore the L-arg/NO
      pathway is responsible, in part, for the vasodilator action of Mg(2+) in human
      forearm resistance vasculature.

PMID- 10965228
TI  - Inhibition of nitric oxide synthesis by systemic N(G)-monomethyl-L-arginine
      administration in humans: effects on interstitial adenosine, prostacyclin and
      potassium concentrations in resting and contracting skeletal muscle.
AB  - We examined whether the formation or the release of the vasodilators adenosine,
      prostacyclin (PGI(2)) and potassium (K(+)) increase in skeletal muscle
      interstitium in response to nitric oxide synthase (NOS) inhibition. Five subjects
      performed one-legged knee extensor exercise at 30 W without (controls) and with
      prior N(G)-nitro-L-arginine methyl ester (L-NAME) infusion (4 mg/kg,
      intravenously). Samples from the interstitial fluid were obtained at rest, during
      exercise and after exercise with the microdialysis technique. Interstitial
      adenosine in controls increased (p<0.05) from 0.11+/-0.03 micromol/l at rest to
      0.48 +/-0.06 micromol/l during exercise. Interstitial adenosine during exercise
      in L-NAME was similar (p>0.05) to controls. The 6-keto-prostaglandin F1alpha
      concentration in controls was 1.17+/-0.20 ng/ml at rest and increased (p<0.05) to
      1.97+/-0.30 ng/ml during exercise and was further elevated (p<0.05) to 2.76+/
      0.38 ng/ml after exercise and these concentrations were not different (p>0.05) in
      L-NAME. The interstitial K(+) concentration in controls increased (p< 0.05) from
      4.1+/-0.1 mmol/l at rest to 9.5+/-0.5 mmol/l during exercise. The interstitial
      K(+) concentration during exercise (6.7+/- 0.4 mmol/l) was lower (p<0.05) in L
      NAME than in controls. The present findings demonstrate that the muscle
      interstitial concentrations of adenosine, PGI(2) and K(+) during exercise are not
      increased with systemic NOS inhibition. Thus, the lack of effect of NOS
      inhibition on the rate of blood flow to contracting human skeletal muscle does
      not appear to be due to compensatory formation or release of adenosine, PGI(2)
      and K(+) in the muscle interstitium. The present study also supports a role for
      PGI(2) in the regulation of blood flow during exercise.

PMID- 10965230
TI  - Blood interleukin-6 and tumor necrosis factor-alpha elevation after
      intracerebroventricular injection of Escherichia coli endotoxin in the rat is
      determined by two opposing factors: peripheral induction by LPS transferred from
      brain to blood and inhibition of peripheral response by a brain-mediated
      mechanism.
AB  - Following intracerebroventricular injection of LPS in rats, IL-6 and TNF-alpha
      appear in peripheral blood. To determine whether these changes are mediated by
      passage of the injected LPS from the brain to the blood, the time course of
      appearance in blood of bioactive LPS after intracerebroventricular injection was
      compared with the time course of appearance of IL-6 and of TNF-alpha in blood.
      Bioactive LPS was detected 30 min after intracerebroventricular injection, the
      first time interval tested. TNF-alpha appeared in peripheral blood at 30 min, IL
      6 at 60 min and both cytokines as well as LPS achieved highest levels at 120 min.
      To determine pharmacokinetics of LPS transfer from brain to blood more precisely,
      radioiodinated LPS was injected intracerebroventricularly. (125)I-LPS was
      detected in blood as early as 5 min after intracerebroventricular injection,
      reached peak levels at about 2 h, and was transferred from brain to blood at a
      rate corresponding to bulk flow (% of brain content per min was 1.40 +/- 0.58 and
      1.00 +/- 0.21% in series 1 and 2, respectively). 70.0% of total injected LPS had
      entered blood by 4 h. However, when administered intravenously (by a programmed
      pump) at the same rate that it enters the blood after intracerebroventricular
      injection LPS induced a much greater cytokine response than when given
      intracerebroventricularly. This paradoxical response was shown in further studies
      to be due to the simultaneous central inhibitory effect of LPS; coinjection of
      intracerebroventricular LPS markedly reduced the peripheral cytokine response to
      intravenous LPS infusion.

PMID- 10965229
TI  - Stress-induced reactivation of Epstein-Barr virus in astronauts.
AB  - Herpesviruses are leading causes of infectious blindness and death in
      immunocompromised individuals. Impaired cellular immunity, which is known to
      result in increased frequency and severity of herpesvirus infections, has been
      demonstrated both during and after spaceflight. Therefore, we examined whether
      Epstein-Barr virus (EBV), a well-characterized latent herpesvirus, undergoes
      reactivation in astronauts. Sera from Shuttle astronauts, taken before and after
      spaceflight, were examined for evidence of EBV reactivation. The geometric mean
      antibody titer to EBV viral capsid antigen (VCA) was significantly increased
      prior to flight compared to baseline (p = 0. 0001). After spaceflight, evidence
      of acute lytic replication was found in which 8- to 64-fold increases in EBV
      early antigen (EA) antibodies occurred without significant increases in
      antibodies to measles virus. Additionally, stress-induced shifts in circulating
      leukocytes and elevated levels of urinary cortisol and epinephrine were found.
      Overall, significant increases in EA or high VCA/EA antibody titers were found in
      8 of 23 (35%) male astronauts and 3 of 5 (60%) female astronauts. These results
      indicate that stress reactivates EBV prior to flight and suggest that acute lytic
      replication of EBV occurs during spaceflight.

PMID- 10965231
TI  - Peripheral effects of methionine-enkephalin on inflammatory reactions and
      behavior in the rat.
AB  - Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central
      nervous system functions. The present study was conducted in order to compare
      peripheral and central effects of Met-Enk on nonspecific immunity, open field
      behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met
      Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw
      edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H(2)O(2)
      production of peritoneal macrophages. Met-Enk-induced immunopotentiation was
      antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary
      naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and
      vertical locomotor activity in the open field that was reversed by i. p.
      administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk
      applied i.p. did not affect the number of writhes in the test of analgesia.
      Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was
      previously shown to be immunostimulatory, enhanced only basal H(2)O(2) production
      of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides,
      i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H(2)O(2) production
      of peritoneal macrophages under basal and stimulated conditions, respectively.
      Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the
      open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was
      sufficient to modulate immune functions did not influence behavior. It may be
      concluded that Met-Enk modulated nonspecific immune responses and open field
      behavior by peripheral mechanisms.

PMID- 10965232
TI  - Strain-dependent association between lateralization and lipopolysaccharide-
      induced IL-1beta and IL-6 production in mice.
AB  - OBJECTIVE: The brain modulates the immune system in an asymmetrical way, as shown
      by the association between paw preference and immune response in the mouse. We
      predicted that the production of cytokines, which are one of the molecular
      pathways for brain-immune interactions, should be linked to lateralization in a
      strain-dependent manner. METHODS: We therefore measured plasma levels of
      interleukin (IL)-1beta and IL-6 after an intraperitoneal injection of
      lipopolysaccharide (LPS) in two strains of mice (C3H and BALB/c) that were
      selected for their different profiles of cytokine production. RESULTS: Plasma
      levels of IL-1beta and IL-6 increased after LPS injection in both strains and
      this increase was dependent on paw preference in BALB/c but not in C3H mice.
      Increased levels of IL-1beta were observed in left-pawed and ambidextrous but not
      in right-pawed mice. For IL-6, the LPS-induced increase was higher in
      ambidextrous than in left- and right-pawed animals. CONCLUSION: Cytokines may
      represent one of the factors responsible for interindividual differences in brain
      immune interactions.

PMID- 10965233
TI  - Central monoamine activity following acute and repeated systemic interleukin-2
      administration.
AB  - Interleukin-2 (IL-2), together with other cytokines, may be involved in
      communication between the immune system and the CNS. Moreover, IL-2 alterations
      have been implicated in psychiatric disorders, and IL-2 immunotherapy may
      engender neuropsychiatric and cognitive disturbances. Given the presumed
      relationship between mood disturbances and monoamine activity, the present
      investigation was undertaken to determine the central monoamine alterations
      associated with acute and repeated systemic IL-2 administration in mice. Acute,
      systemic IL-2 (0.55-17.6 x 10(3) IU) did not influence plasma adrenocorticotropic
      hormone or corticosterone levels, but increased the utilization of norepinephrine
      (NE) within the paraventricular nucleus of the hypothalamus. In contrast to the
      effects of acute IL-2 administration, when administered repeatedly (for 7 days),
      IL-2 increased NE utilization within the median eminence plus arcuate nucleus and
      in the hippocampus, and to a lesser extent in the central amygdala and medial
      prefrontal cortex. These changes in utilization were accompanied by increased
      levels of NE within the median eminence plus arcuate nucleus and central
      amygdala, and reduced NE within the locus coeruleus. As well, serotonin (5
      hydroxytryptamine; 5-HT) levels were altered within the hippocampus and
      prefrontal cortex, and dopamine turnover was reduced within the caudate and
      substantia nigra. The finding of altered central neurotransmitter activity needs
      to be considered in the context of the marked cognitive/memory impairments, as
      well as the neuropsychiatric symptoms, which are associated with IL-2
      immunotherapy in humans.

PMID- 10965234
TI  - Lipopolysaccharide-induced leptin release is not mediated by nitric oxide, but is
      blocked by dexamethasone.
AB  - The adipocyte hormone, leptin, has homology with tumor necrosis factor-alpha (TNF
      alpha) and the leptin receptor (OB-Rb) has homology with the interleukin(IL)-6
      receptor. Lipopolysaccharide (LPS) from gram-negative bacteria stimulates the
      release of many pro-inflammatory cytokines, such as TNF-alpha, IL-1 and IL-6,
      among others. To test the hypothesis that LPS would also stimulate the release of
      leptin, LPS (0.6 mg/kg) was injected intravenously into conscious male rats
      bearing external jugular venous catheters. Vehicle (0.9% NaCl) was injected into
      control animals. Blood samples (0.3 ml) were drawn immediately before injection
      and every 10 min afterwards for 120 min. Plasma leptin concentrations increased
      gradually in the LPS-treated rats, reaching a peak at 120 min of nearly twice the
      starting level. To determine if this release was mediated by nitric oxide (NO),
      nitroarginine methyl ester (NAME), an inhibitor of NO synthase, was injected at
      doses of 11 or 23 mg/kg (i. v.). The lower dose decreased plasma leptin slightly,
      whereas the higher dose of NAME increased plasma leptin at 110 min but had no
      effect on LPS-induced leptin release. On the other hand, dexamethasone (DEX)
      (0.85 mg/kg), a synthetic glucocorticoid, injected 15 min before LPS, decreased
      LPS-induced leptin release by 80% (p < 0.001). The results indicate that LPS is a
      stimulant of leptin release, that NO has little control over basal or LPS-induced
      leptin release, but that glucocorticoids, epitomized by DEX, largely block LPS
      induced leptin release. Increased release of leptin during infection may
      contribute to the decreased feeding, altered hormonal release and metabolic
      changes that occur during infection.

PMID- 10965235
TI  - Modulatory role of the epinergic system in the neuroendocrine-immune system
      function.
AB  - It is well recognized that the reciprocal interaction established between the
      immune and neuroendocrine systems is crucial for the homeostatic adaptation of
      individuals during septicemia. In the present study, using an in vivo rat model,
      we investigated the degree of participation of central and peripheral epinergic
      systems in the modulation of the hypothalamic-pituitary-adrenal and immune axes'
      functions during endotoxemia. For this purpose, acute endotoxemia was induced in
      adult male rats pretreated intraperitoneally with either different inhibitors of
      phenylethanolamine-N-methyltransferase (PNMT) [which are active either
      peripherally (SKF 29661) or both peripherally and centrally (SKF 64139), thus
      lowering epinephrine (EPI) synthesis] or vehicle only (CTRL). Twelve hours after
      pretreatment, animals were intraperitoneally injected with vehicle alone (basal)
      or vehicle containing bacterial lipopolysaccharide (LPS) and sacrificed 2 h
      later. A significant (p < 0.05 vs. the respective basal value) hypoglycemia was
      found in all groups studied. No pretreatment modified basal plasma
      adrenocorticotropic hormone (ACTH), glucocorticoid and cytokine concentrations.
      Endotoxin-stimulated ACTH secretion was severalfold (p < 0.05) higher than the
      respective basal value in CTRL and in SKFs-pretreated rats; however, the plasma
      ACTH levels after LPS were significantly (p < 0.05 vs. CTRL and SKF-29661 values)
      reduced in SKF-64139-pretreated rats. All groups studied showed an appropriate
      adrenal response to endotoxin challenge. Although no differences were found in
      basal anterior pituitary (AP) ACTH content among groups, LPS treatment
      significantly (p < 0.05 versus the respective basal value) decreased AP ACTH in
      CTRL and SKF 29661 groups. No pretreatment modified the basal medial basal
      hypothalamus (MBH) corticotropin-releasing hormone (CRH) content. Conversely, SKF
      64139 pretreatment significantly (p < 0.05 vs. CTRL and SKF 29661 values) reduced
      basal median eminence (ME) CRH content, and LPS administration significantly (p <
      0.05) decreased ME CRH in CTRL and SKF-29661-pretreated rats. SKF 64139
      pretreatment significantly (p < 0.05) enhanced basal MBH and ME arginine
      vasopressin (AVP) contents. LPS administration significantly (p < 0.05) decreased
      MBH AVP in CTRL and SKF-29661-pretreated rats and diminished (p < 0.05 vs. basal
      values) ME AVP in all groups. The plasma tumor necrosis factor alpha (TNFalpha)
      concentrations were enhanced severalfold (p < 0.05 vs. basal values) after LPS
      treatment in CTRL rats, but not in SKFs-treated animals. In order to explore the
      reduced cytokine release after LPS in PNMT-inhibited rats, additional ex vivo
      experiments were performed by using peripheral mononuclear cells (PMNC) from both
      CTRL and SKF-29661-pretreated rats. The results of these experiments confirmed an
      immune dysfunction after inhibition of peripheral EPI synthesis; in fact, basal
      and concanavalin-A-stimulated TNFalpha secretions were significantly (p < 0.05)
      lower in SKF-29661-treated than in CTRL PMNC, while, interestingly, addition of
      EPI (10(-7) M) to the medium fully restored these effects. These data demonstrate
      that: (1) the mechanism whereby LPS-induced hypoglycemia was independent of
      epinergic activity; (2) selective central inhibition of epinergic function
      reduced endotoxin-stimulated ACTH secretion, an effect that could mainly be due
      to a decrease in CRH-ergic activity; (3) the central epinergic system positively
      and negatively modulates CRH- and AVPergic functions, respectively, and (4)
      inhibition of peripheral PNMT activity reduced immune system function in vivo and
      ex vivo. It is further suggested that low peripheral levels of EPI could be
      beneficial for the body's defense mechanisms during endotoxic shock.

PMID- 10965236
TI  - Are prior head injuries or diagnostic X-rays associated with glioma in adults?
      The effects of control selection bias.
AB  - The causes of glioma, the most common type of primary malignant brain tumors, are
      poorly understood. This study compares personal histories of head injury and
      diagnostic radiation procedures of the head and neck among 476 adults newly
      diagnosed with glioma in the San Francisco Bay Area between August of 1991 and
      April of 1994 (82% of all those diagnosed during that time period) with 462 age-,
      gender-, and ethnicity-frequency-matched controls (63% of those eligible from
      random digit dialing). In addition, limited information was obtained from 101
      controls during a brief telephone interview conducted with controls who declined
      participation in the lengthy in-person interview. Controls who participated in
      the full interview were much more likely than controls who only completed the
      telephone interview to report head injury [odds ratios (OR) and 95% confidence
      intervals (CI) were 2.3 (1.0-4.9) and 3.0 (1.6-5.8) for women and men,
      respectively]. The OR for any head injury in cases versus controls who completed
      the full interview was 0.9. However, OR for any head injury in cases versus both
      control groups was 1.3, 95% CI (1.0-1.7), and the OR for head injury for which
      the subject sought medical attention was 1.1, 95% CI (0.8-1.4). Among subjects
      completing the full interview, cases who responded by self-report were less
      likely than controls to report prior non-dental head and neck X-rays (OR = 0.7;
      95% CI: 0.5-1.0). However, stratification by respondents' history of head injury
      indicated no difference in history of head and neck X-ray among those without
      prior head injury; OR 0.9; 95% CI (0.6-1.2). Cases and controls shared a very
      similar history of dental procedures and frequency of dental visits. These
      results suggest that head injury requiring medical attention, dental visits, or
      non-dental diagnostic X-rays to the head and neck are not important contributors
      to the risk of adult glioma and reveal some of the methodological obstacles
      encountered in forming convincing conclusions about these risk factors for brain
      tumors.

PMID- 10965237
TI  - A single question about prior stroke versus a stroke questionnaire to assess
      stroke prevalence in populations.
AB  - BACKGROUND: False-positive and false-negative answers to screening questions
      influence prevalence and incidence estimations for stroke in population studies.
      Despite frequent use in screening, only a few studies have examined causes and
      influence of incorrect self-reports. We compared the rates of false-positive and
      false-negative answers to a single question about prior stroke to those of the
      Stroke Symptom Questionnaire (SSQ), a newly developed instrument based on 6
      symptom questions. Differences in stroke prevalence estimations and risk factors
      for incorrect reports are described. METHODS: The MEMO study (Memory and
      Morbidity in Augsburg Elderly) examines cognitive function and neurodegenerative
      diseases in an elderly population (n = 384) in southern Germany. All participants
      filled in the symptom questionnaire, received a neurological examination and a
      neuropsychological test battery. Medical records were obtained for event
      validation of subjects positive on screening and those negative on screening with
      symptoms suggesting a cerebrovascular event during examination. RESULTS:
      Prevalence of total stroke was 5. 3% using a single screening question and 6.8%
      using the questionnaire. The false-negative rate was higher for the single
      question approach (34.2 versus 10.5%). It was strongly influenced by gender and
      cognitive function. The questionnaire had a higher false-positive rate than the
      single question. Based on the results, we established question combinations that
      best served three different research scenarios (frequency estimation, risk factor
      analysis, control selection), relevant to stroke research in population studies.
      CONCLUSIONS: A single screening question for stroke in the past with event
      validation by medical records underestimates stroke frequency in population
      studies by about 30%. Use of a number of questions for key symptoms combined with
      a general stroke question, as in the SSQ, improves the completeness of event
      ascertainment and allows the detection of stroke and transient ischemic attack at
      the same time.

PMID- 10965238
TI  - Incidence of stroke on Kinmen, Taiwan.
AB  - This study aims to assess the incidence, case-fatality rate and risk factors of
      stroke on Kinmen Island, Taiwan, from 1993 to 1996. A population-based stroke
      survey was carried out in 1993 and 1996 to collect data on all subjects in the
      population aged 50 years and older residing on Kinmen. There were 63 stroke
      events (53 first ever and 10 recurrent) identified in this period. The average
      annual incidence rate of first-ever stroke for people aged 50 years or older was
      527 per 100,000 population (95% confidence interval, CI, 297-757). The 28-day
      case-fatality rate was 24.5% (95% CI 12.9-36. 1%) for first-ever stroke and 60%
      (95% CI 29.6-90.4%) for recurrent stroke. Multivariate analyses performed with
      the Cox proportional hazard model revealed the following risk factors to be
      independent predictors of stroke: hypertension, diabetes and alcohol use. The
      incidence and case- fatality rate of stroke on Kinmen is similar to that of
      several other countries. Hypertension is the most common risk factor in this
      population. Due to a relatively small number of outcome events, these findings
      require confirmation.

PMID- 10965239
TI  - Recent trends of stroke mortality in Hong Kong: age, period, cohort analyses and
      the implications.
AB  - This study describes the time trend of cerebrovascular disease (CVD) mortality
      during the period 1976-1995 in Hong Kong and explores the period and birth cohort
      effects using Poisson regression models with correction for overdispersion of
      data. A clear downward trend was observed for age-adjusted CVD mortality rate in
      both sexes. It decreased from 84 per 100,000 to 41 per 100,000 among men (a 51%
      drop), and from 56 per 100,000 to 35 per 100,000 among women (a 38% drop). The
      rate of decline was in general greater in the second decade and among males,
      resulting in a significant downward trend for the male-to-female rate ratio. Both
      the period of death and the birth cohort showed a significant effect on the
      reduction in mortality rates, but the latter seemed to have a more substantial
      influence. However, an increasing trend was observed among younger males in the
      second decade, and the protective cohort effect seemed to be waning for the more
      recent cohorts in both sexes. Closer monitoring of the situation in the next
      years is warranted.

PMID- 10965240
TI  - Case-control study of Meige's syndrome. Result of a pilot study.
AB  - A pilot case-control study was conducted to identify possible risk factors for
      Meige's syndrome. Patients with Meige's syndrome and age- and sex-matched
      controls suffering from other neurological diseases were recruited from the
      Movement Disorders Clinic and Neurology Outpatient Department of the All India
      Insititute of Medical Sciences. All participants were interviewed and information
      regarding psychiatric and medical illnesses, use of medications, exposure to
      fumes, dust and pets, characteristics such as marital status, socio-economic
      status, alcohol, tea/coffee use, tobacco use, betel nut chewing and family
      history of neurodegenerative diseases among first-degree relatives was
      ascertained. We found that betel nut with tobacco chewing was a significant
      predictor for Meige's syndrome (adjusted odds ratio 7.4, 95% confidence interval
      = 1.0-59. 82). The role of local irritation or the effect of some chemicals in
      tobacco and betel nuts needs further evaluation of the pathogenesis of Meige's
      syndrome.

PMID- 10965241
TI  - Regional north american annual meeting of the world federation of neurology -
      research group on neuroepidemiology. san diego, calif., may 5, 2000
AB  - Copyright 2000 S. Karger AG, Basel

PMID- 10965242
TI  - Changes in deviation following correction of hyperopia in children with fully
      refractive accommodative esotropia.
AB  - Changes in deviation may occur following the correction of hyperopia in children
      with accommodative esotropia. We analyzed possible factors involving the
      development of changes in deviation. We examined 49 children (23 boys and 26
      girls) who had fully refractive accommodative esotropia at the age of 3 or 4
      years. All children wore glasses to correct the fully cycloplegic refractive
      errors. At the age of 10 or 11 years, 28 (57.1%) of these children had good
      alignment, 12 (24.5%) developed partial accommodative esotropia and 9 (18.4%)
      developed consecutive exotropia. The age at onset of esotropia, age at initial
      visit, and refraction, deviation and presence of stereopsis, as determined by the
      Titmus test using a fly at the initial visit, were similar among the three
      groups. In the consecutive exotropia group, amblyopia at the initial visit was
      significantly higher (89%) than that of the good alignment group (50%). The age
      at the start of the correction, and the refraction, amblyopia and presence of
      fusion (10 or 11 years) were almost equal among the three groups. We conclude
      that some children with fully refractive accommodative esotropia associated with
      amblyopia at the age of 3 or 4 years may be predisposed to developing consecutive
      exotropia.

PMID- 10965243
TI  - Unusual visual evoked potentials in patients with age-related macular
      degeneration.
AB  - Among a series of patients with age-related macular degeneration (ARMD), a few
      individuals could be identified showing larger amplitudes of pattern reversal
      visual evoked potentials (prVEP) after stimulation of a central 3 degrees field
      compared to stimulation of a 13 degrees field although in the majority of ARMD
      patients and in normals, VEP amplitudes increased with increasing field size. An
      analysis of prVEPs recorded after stimulation of different macular zones showed
      that the 3 degrees central area and the perifoveal zone contributed differently
      to the 13 degrees response or macular response. Perifoveal activity in this
      subgroup of ARMD patients seemed to mask the foveal contribution to the macular
      prVEP. The cortical magnification factor in ARMD may be higher than in normal
      controls. Small-field stimulation techniques are therefore also recommended in
      patients with central retinal pathology.

PMID- 10965244
TI  - Corneal refractive changes after acrysof lens versus PMMA lens implantation.
AB  - PURPOSE: Do foldable acrylic lenses yield not only reduced posterior capsular
      opacification but also significant refractive advantages? PATIENTS AND METHODS:
      147 cataract patients including 47 with spherical corneas and 100 with
      preoperative astigmatism of 0.8 +/- 0. 7 dpt were treated in one of two ways: 70
      patients received 5.5-mm Acrysof lens implants through 3.2-mm outer and 4-mm
      inner temporal clear corneal openings (stretch incision); 77 patients received 5
      mm PMMA lenses through temporal clear corneal incisions of 4.1-mm outer and 6.5
      mm inner diameter incisions. Corneal topography was examined in all patients
      before the operations as well as 3 days and 6 months after the operations.
      RESULTS: 6 months after the operations, we observed a surgically induced
      astigmatism of 0.4 +/- 0.2 dpt for the 3.2-mm incisions compared to 0.8 +/- 0.7
      dpt for the 4.1-mm incisions; evaluation according to Holladay of the
      preoperative spherical corneas yielded a with-the-wound change of 0.0 +/- 0.3 dpt
      after 3.2-mm incisions versus 0.6 +/- 0.7 dpt after 4.1-mm incisions. The
      difference in astigmatism for the two types of incisions was statistically
      significant (p = 0.001). CONCLUSION: Acrysof lens implantation is especially
      useful for patients with spherical corneas because of avoidance of postoperative
      astigmatism. The 4. 1-mm corneal incision using PMMA lens implants can be used on
      the steep meridian to reduce preoperative astigmatism.

PMID- 10965245
TI  - Contamination of contact-lens-related sources with Pseudomonas aeruginosa.
AB  - The studies conducted sought to estimate contamination of contact lens (CL)
      storage cases and commercial solutions with Pseudomonas aeruginosa as well as to
      investigate everyday sources, which the CL wearer uses or comes into contact
      with. The studies revealed that 13. 1% of storage lens cases and 5.1% of
      commercial solutions in use were positive for the bacterium. Ten hermetically
      sealed CL solutions were tested for possible contamination, but these all proved
      to be sterile. In addition, environmental samples, of both a solid and liquid
      nature, yielded relatively high contamination rates with this opportunistic
      bacterium. Results showed that common sources, which the CL wearer is in contact
      with, possess P. aeruginosa and this may indeed predispose to corneal infections.

PMID- 10965246
TI  - Effect of beta-blocker eyedrops on corneal epithelial barrier function.
AB  - To investigate the long-term effect of a topically applied beta-blocker on human
      corneal epithelium, the corneal epithelial barrier function and the superficial
      cell area of the corneal epithelium were evaluated. Seventeen normal healthy
      volunteers (without medication), 7 cataract patients (treated with pyrenoxine
      eyedrops) and 7 glaucoma or ocular hypertension patients (treated with 0.5%
      timolol maleate) were assigned to this study. The eyedrops had been used on a
      daily basis for at least 3 months. In the evaluation of corneal epithelial
      barrier function, fluorescein uptake was measured using a slitlamp
      fluorophotometer after application of 3 microl of 0.5% fluorescein for 10 min. In
      the evaluation of the superficial cell area, the central corneal epithelium was
      measured by tandem scanning confocal microscopy (TSCM). The healthy control and
      timolol groups were compared. Corneal fluorescein uptake in the healthy control,
      pyrenoxine and timolol groups was 20.3 +/- 3.2, 21.5 +/- 4.0 and 76.2 +/- 30.0
      ng/ml (mean +/- standard error), respectively. There was a significantly higher
      fluorescein uptake in the timolol group compared to the pyrenoxine group (p =
      0.0088) and the healthy control group (p = 0.0055). TSCM showed no significant
      difference in the superficial cell areas of the corneal epithelium between the
      healthy control and timolol groups. beta-Blocker eyedrops decreased the corneal
      epithelial barrier function. Their application was not accompanied by any
      biomicroscopic change in the superficial cell area.

PMID- 10965247
TI  - Influence of human immunodeficiency virus status on the clinical history of
      herpes simplex keratitis.
AB  - Human immunodeficiency virus (HIV) infection is associated with a wide spectrum
      of systemic and ocular infectious diseases. Little is known about its association
      with herpes simplex keratitis (HSK) in this geographical region (South India). A
      retrospective study was undertaken to analyze this association in a cohort of 30
      virologically proven recurrent HSK cases. Laboratory methods included herpes
      simplex virus (HSV) isolation, HSV antigen detection and tear secretory IgA or
      HSV DNA detection while commercial ELISA kits detected HIV infection. The
      rationale behind the HIV screening was to assess the role of HIV with increased
      HSK recurrences. Confirmed HIV seropositivity was 16.7% in recurrent HSK cases as
      against 3.3% in the matched first-episode HSK cases (p < 0.05, Fisher's exact
      test). Our observations on the features of herpetic keratitis in HIV-proven
      patients, though based on a small number of cases, raise the question whether the
      immunological abnormalities associated with HIV/AIDS may affect the clinical
      course of HSK.

PMID- 10965248
TI  - Connective tissue growth factor in retrocorneal membranes and corneal scars.
AB  - We studied the localization and distribution of connective tissue growth factor
      (CTGF) in corneal scar tissue and membranes using in situ hybridization in 8
      corneas from keratoplasty and 4 normal corneas. Identification of the cells was
      done with immunohistochemistry for SM-alpha-actin, vimentin, and Lu5. CTGF mRNA
      was found in activated corneal fibroblasts in 7 of 8 scars, 7 of 8 retrocorneal
      membranes and 2 subepithelial membranes, whereas the control corneas showed no
      CTGF mRNA expression. Vimentin was positive in all scars, retrocorneal and
      subepithelial membranes, SM-alpha-actin in 7 of 8 scars and 6 of 8 retrocorneal
      membranes. These results suggest that CTGF plays a crucial role in corneal wound
      healing and membrane formation.

PMID- 10965249
TI  - Hypothyroidism and primary open-angle glaucoma.
AB  - OBJECTIVE: To test if there is an association between hypothyroidism and primary
      open-angle glaucoma (POAG) and the utility of routine study of thyroid function
      in these patients. METHODS: The study was conducted in a case-control fashion.
      Seventy-five consecutive patients with a previous diagnosis of POAG and 75
      control patients were prospectively evaluated for hypothyroidism. The levels of
      thyroid-stimulating hormone and free thyroxin were measured. RESULTS:
      Hypothyroidism was revealed in only 2 patients with previous diagnosis of POAG
      (2.67%) and 3 patients of the control group (4%). CONCLUSIONS: As we have not
      been able to demonstrate the previously reported relationship between
      hypothyroidism and POAG, we cannot recommend the systematic screening for
      hypothyroidism in patients with POAG.

PMID- 10965250
TI  - Effect of melatonin on lenticular calcium and magnesium in rats exposed to
      ultraviolet radiation.
AB  - Six-week-old rats received 8 kJ/m(2) ultraviolet B (UVB) for 15 min. For the
      intervention in cataract development, intraperitoneal injection of melatonin (4
      mg/kg daily for 1 week) following UVB exposure was performed. Lenticular calcium
      and magnesium levels were determined in UVB + melatonin, UVB and control groups.
      One week after exposure, significantly more cataractous changes were observed in
      the UVB group than the UVB + melatonin group. The mean lens calcium and magnesium
      levels for the UVB group were significantly higher than those for the control and
      the UVB + melatonin groups. There were no significant differences between the
      control and the UVB + melatonin groups for the mean lens calcium and magnesium
      levels.

PMID- 10965251
TI  - Electroretinographic assessment of early changes in ocular siderosis.
AB  - We examined a patient with an iron intraocular foreign body and recorded
      electroretinograms (ERGs) before and after the removal of the foreign body by
      vitrectomy. The amplitudes of the rod and cone ERGs and the oscillatory
      potentials (OPs) in the injured eye were reduced before the operation. In
      addition, the photopic on-responses (b wave) were more reduced than off-responses
      (d wave). One year after surgery, the amplitudes of the rod, cone and photopic on
      and off-responses were markedly improved to within the low normal limit.
      However, the OP amplitudes remained unchanged with lower values. These findings
      suggest that iron retinotoxicity leads to a dysfunction of all layers but the
      changes may be reversible in the early period of the disease. The late period
      iron toxicity produces more severe damage to the inner retina than the outer
      retina.

PMID- 10965252
TI  - Bilateral angle closure glaucoma and visual loss precipitated by antidepressant
      and antianxiety agents in a patient with depression.
AB  - A 71-year-old woman with depression had been treated with an antidepressant
      (maprotiline) and antianxiety agents (clotiazepam and alprazolam). She had
      previously complained of ocular pain and blurred vision. However, thorough ocular
      examination was not performed at those times. On examination, visual acuity was
      no light perception OD and hand motion OS. Intraocular pressures were 33 mm Hg
      OU. Moderately dilated pupils, atrophic irises, shallow anterior chambers and
      closed angles were seen in both eyes. Despite treatment, her visual acuity
      decreased to no light perception bilaterally. Psychiatrists and ophthalmologists
      should be aware that antidepressants and antianxiety agents can precipitate angle
      closure glaucoma in susceptible eyes.

PMID- 10965253
TI  - Idiopathic multiple serous detachments of the retinal pigment epithelium followed
      by bilateral central serous chorioretinopathy: a case report.
AB  - An uncommon case of a 25-year-old woman affected by bilateral idiopathic multiple
      serous detachments of the macular retinal pigment epithelium is described. During
      the fluorescein angiography follow-up, in either macular area one of these
      detachments resulted in a typical central serous chorioretinopathy active leakage
      point. These findings detail that idiopathic serous detachments of the retinal
      pigment epithelium may represent predisposing changes for the development of
      macular neurosensory retinal detachment.

PMID- 10965255
TI  - Case study of an oculodentodigital (Meyer-Schwickerath) syndrome.

PMID- 10965254
TI  - Anterior uveal and episcleral metastases from carcinoma of the breast.
AB  - Breast carcinoma is the most common primary tumor producing intraocular
      metastasis. Metastases to the iris and ciliary body are relatively rare. The
      authors report a case of a 61-year-old lady, operated for carcinoma of the left
      breast 3 years back, who presented with symptoms and signs of acute narrow-angle
      glaucoma in the right eye. A diffuse whitish plaque-like mass in the upper nasal
      quadrant of the iris with an episcleral nodule on the limbus in the corresponding
      area and all the signs of acute narrow-angle glaucoma were present in the right
      eye. Intraocular pressure was controlled medically. Fine-needle aspiration
      cytology from the episcleral nodule showed malignant cells. Histopathology of the
      excised nodule showed metastatic poorly differentiated carcinoma, and the
      cellular pattern was similar to the carcinoma of the breast. There was no other
      metastasis anywhere in the body. Fine-needle aspiration cytology from an external
      lesion of the eye is a less invasive and easier procedure than paracentesis to
      diagnose the metastatic nature of the lesions. The rare features in our case are
      the clinical presentation as acute glaucoma and the ocular structures being the
      first and only site of metastasis.

PMID- 10965256
TI  - The characteristics of congenital hypertrophy of retinal pigment epithelium in
      Turcot syndrome.

PMID- 10965257
TI  - Quantification of osteoclastic resorption of the bovine otic capsule in vitro by
      an enzyme-linked immunosorbent assay.
AB  - The bony shell surrounding the inner ear is known to have a very pronounced
      centripetal inhibition of remodelling in vivo, with almost no bone turnover
      immediately adjacent to the perilymphatic spaces and a gradually increasing
      turnover rate towards outer parts of the bony otic capsule. By the use of in
      vitro markers of bone resorption, including an enzyme-linked immunosorbent assay
      for quantification of type I collagen degradation and a colorimetric enzyme assay
      for quantification of osteoclast tartrate-resistant acid phosphatase activity,
      this study demonstrates that there are no ex vivo differences in bone matrix
      resorption between the inner and outer parts of the otic capsule when exposed to
      seeded osteoclasts from rabbits. Thus, the unique spatial distribution of
      perilabyrinthine bone turnover is not caused by a shift in resorbability from
      inner to outer capsular bone that is due to inherent bone quality differences
      particular to these bone compartments. More likely, the sustained action of some
      intravital 'field force', originating from the inner ear spaces, is responsible
      for the unique spatial distribution of the otic capsular bone turnover found in
      vivo. Though the character of this force is not yet defined, it is appealing to
      relate it to the large electromagnetic potential gradient present in the inner
      ear.

PMID- 10965258
TI  - Development of monovalent ions in the endolymph in mouse cochlea.
AB  - The present study was designed to clarify the chronological developmental process
      of monovalent ions (Na(+), K(+), Cl(-)) in the endolymph of the mouse in relation
      to the development of the endocochlear potential (EP). The EP and ionic
      concentrations were measured simultaneously with the ion-sensitive double
      barreled microelectrodes from the scala media of the basal turn. The EP increased
      abruptly 7 days after birth (DAB) and reached approximately 80 mV 14 DAB. In the
      earliest postnatal days, the endolymphatic Na(+) concentration was significantly
      higher than that in adult mice, however, the K(+) and the Cl(-) concentrations
      were lower. The concentrations of all the monovalent ions in endolymph reached
      adult levels at 7 DAB when the EP was still under 20 mV. These data strongly
      suggest the presence of a different mechanism between the production of
      monovalent ions, especially of high K(+) in the endolymph and that of EP.

PMID- 10965259
TI  - Biocompatibility testing of new polymers in a moving implant bed.
AB  - Total reconstruction of the auricle requires a skillful surgical technique and an
      appropriate material for the shape-supporting frame. Up to now, there is no such
      material apart from autologous rib cartilage. The combination of chronic
      microtraumatization of adjacent tissue caused by the mobility of an implant bed
      such as the auricle and the foreign-body reaction to currently available
      artificial polymers frequently results in extrusion. In our animal model (rats),
      polymers of different elasticity were implanted in a moving implant bed to
      analyse differences in foreign-body reaction related to implant elasticity. The
      results were significantly better for a rather stiff control material (porous
      polyethylene). A contributing factor may be better fixation of the implant
      material by tissue ingrowth into its micropores.

PMID- 10965260
TI  - Scala vestibuli insertion in cochlear implantation: a valuable alternative for
      cases with obstructed scala tympani.
AB  - Insertion of a sufficient number of electrodes is important for a successful use
      of cochlear implants. We investigated the results of scala vestibuli insertion
      for cochlear implantation in cases of obstructed scala tympani. In a series of
      200 cochlear implantations, scala vestibuli insertion was successfully performed
      in 4 cases with obstruction of the scala tympani. Etiologies included a temporal
      bone fracture, severe otosclerosis and malformations of the cochlea. The maximum
      insertion depth obtained via the scala vestibuli was 30 mm. Postoperative results
      were comparable to patients in whom conventional scala tympani insertion was
      performed. No adverse effects related to the site of insertion were observed.
      Scala vestibuli insertion offers a valuable alternative in cases of obstructed
      scala tympani that can be employed for a variety of etiologies.

PMID- 10965261
TI  - Acquired and congenital cholesteatoma: determination of tumor necrosis factor
      alpha, intercellular adhesion molecule-1, interleukin-1-alpha and lymphocyte
      functional antigen-1 in the inflammatory process.
AB  - The molecular and cellular factors resulting in the pathologic features of
      acquired and congenital cholesteatomas are not completely known. Recently,
      proinflammatory cytokines like interleukin-1 alpha (IL-1 alpha) and tumor
      necrosis factor-alpha (TNF-alpha) have been shown to induce bone resorption, in
      vitro. To elucidate the key molecules involved in bone resorption and cell
      infiltration associated with cholesteatoma, we examined the in vivo levels of IL
      1 alpha and TNF-alpha, intercellular adhesion molecule-1 (ICAM-1) and lymphocyte
      functional antigen-1 (LFA-1) in acquired and congenital cholesteatomas, by
      reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ELISA.
      Increased levels of IL-1 and TNF-alpha were detected in both types of
      cholesteatomas as compared to normal skin. Increased ICAM-1 expression and LFA-1+
      cells were detected in acquired but not congenital cholesteatoma. Strong
      correlation was detected between TNF-alpha and bone resorption in both types of
      cholesteatoma, and between TNF-alpha and ICAM, TNF-alpha and severity of
      infection, or cell infiltration in acquired cholesteatoma. No correlation existed
      between various parameters and IL-1 alpha. These results suggest that TNF-alpha
      may play a crucial role in the pathogenesis of both acquired and congenital
      cholesteatomas by regulating bone resorption and cell infiltration.

PMID- 10965262
TI  - Nystagmus findings in healthy subjects examined with infrared videonystagmoscopy.
AB  - The increased use of video systems for the detection of nystagmus is a new
      diagnostic tool in the diagnosis of patients with vestibular disorders. Small
      video cameras mounted in a light sealed mask visualize the eyes which are
      illuminated with infrared light. Compared to the well-established use of Frenzel
      glasses the patient has no visual references at all. This new technique requires
      standards for normal limits. Thirty subjects between 20 and 78 years of age with
      no history of vestibular disorders were examined with infrared video-oculoscopy
      with the gaze in primary position, after head-shake and in supine position with
      head torsion and Dix-Hallpike positions backward and forward according to a
      standardized procedure at our department. Two subjects had spontaneous nystagmus,
      but nystagmus after head-shake was not found in any. No subject had torsional
      nystagmus in the Dix-Hallpike positions. In the elderly subjects horizontal
      nystagmus in head hanging position was a frequent finding.

PMID- 10965263
TI  - Superficial siderosis of the central nervous system. A case report on examination
      by ECoG and DPOAE.
AB  - This is a case of superficial siderosis of the central nervous system (SSCN). The
      diagnosis of SSCN was based on the result of T2-weighted magnetic resonance
      imaging and on suggestive clinical manifestations. The pure-tone audiogram showed
      bilateral progressive sensorineural hearing loss with a poor speech
      discrimination score and Jerger type IV. The remarkable elevation of the
      detective threshold of cochlear microphonics on electrocochleography was found
      and distortion product otoacoustic emission (DPOAE) showed no response: These
      electrophysiologic examinations, including electrocochleography and DPOAE,
      revealed that the progressive sensorineural hearing loss in this case was caused
      by both retrocochlear and cochlear damages.

PMID- 10965264
TI  - Lymphoma in the ear.
AB  - BACKGROUND: Malignant tumors of the ear are rare. The most common malignant
      tumors are squamous cell carcinomas and adenocarcinomas. Lymphoma in the ear is
      rare. METHODS: We report 2 cases of a primary presentation of a lymphoma of the
      ear. The literature since 1947 is reviewed. RESULTS: An 83-year-old woman with an
      anaplastic large cell lymphoma of the skin of the external auditory meatus and a
      75-year-old man with a B-cell non-Hodgkin's lymphoma of the mastoid process are
      presented. The literature review shows that only 16 cases of lymphomas of the ear
      have been reported so far. CONCLUSIONS: In a case of therapy-resistant otitis
      and/or peripheral facial paralysis malignancy should be excluded by computer
      tomography of the mastoid. For histopathological diagnosis unfixed specimens are
      preferable. Uniform treatment of lymphomas of the ear has not been established.

PMID- 10965265
TI  - Bilateral parotid gland basal cell adenomas. Case report.
AB  - We report a 65-year-old female with basal cell adenomas arising in the left and
      right parotid glands and review the literature. Diagnosis was based on clinical
      features, ultrasonographic and CT findings as well as histopathological
      examination. Parotid tumours usually arise on one side and bilateral occurrence
      is rare, accounting for 1-3% of all parotid tumours. Most bilateral parotid
      tumours are Warthin's tumours and pleomorphic adenomas, and bilateral basal cell
      adenomas of the parotid glands are very rare and only 5 cases including ours have
      been reported. The exact mechanisms contributing to the development of bilateral
      parotid tumours remain unknown. We speculate on the involvement of environmental
      and genetic factors since the histological features of both parotid tumours are
      identical in most cases.

PMID- 10965266
TI  - Epithelial-myoepithelial carcinoma of the nasopharynx.
AB  - We present a patient with a rare epithelial-myoepithelial carcinoma of the
      nasopharynx with a typical biphasic histopathologic pattern. Immunohistochemical
      findings support the concept that the inner cells differentiate to ductal
      epithelium and the outer cells to myoepithelium. In this patient complete
      excision of the tumor and reconstruction with a pedicled sternocleidomastoid
      myocutaneous flap were performed. A DNA diploid pattern from flow cytometric
      study indicates a favorable prognosis. There was no recurrence nor metastasis for
      55 months.

PMID- 10965267
TI  - Axillary nerve injuries in children.
AB  - Isolated axillary nerve injury is uncommon, particularly in children. The motor
      deficit of shoulder abduction may not recover spontaneously and can be a
      substantial handicap. Detection may be difficult initially, as the injury is
      masked by trauma such as head injury, and concomitant shoulder injury requiring
      immobilization. After mobilization, patients learn to partially compensate by
      using alternate muscles. There are few reports of surgical management of this
      nerve injury. Most concern predominantly adults, and the results are mixed with
      on average slightly greater than half having a good recovery (defined as grade 4
      5 Medical Research Council muscle power). We present our experience with 4
      pediatric patients who had axillary nerve injury. Three patients had an
      interposition nerve graft, and 1 patient underwent neurolysis. All patients
      recovered to grade 4-5 deltoid muscle power. Children with an axillary nerve
      injury which fails to recover spontaneously by 4-6 months should strongly be
      considered for surgical exploration.

PMID- 10965268
TI  - Neonatal cervical osteomyelitis with paraspinal abscess and Erb's palsy. A case
      report and brief review of the literature.
AB  - An unusual case of pyogenic cervical osteomyelitis is reported in a newborn who
      immediately after birth had no movements in the left shoulder. There was a
      fullness in the left cervical region. Left Erb's palsy due to an unrecognized
      birth trauma was diagnosed in a peripheral hospital. Later, the child developed
      fever and a significant swelling in the left cervical region. On transfer to our
      institution, the X-rays of the cervical spine, ultrasound and computed tomography
      (CT) established the diagnosis of C(6) cervical osteomyelitis and paraspinal
      abscess which extended to the posterior triangle of the neck. The abscess was
      drained, and the lamina and lateral mass of the C(6) vertebra were debrided.
      Staphylococcus aureus was grown from the pus. The patient was put on long-term
      antibiotics to which he responded very well, and he became asymptomatic. In the
      immediate post-operative period, some movements at the left shoulder were noted,
      and at 6-month follow-up in the out-patient clinic, the child was virtually
      normal with near-complete regeneration of the C(6) lamina and lateral mass.

PMID- 10965269
TI  - Cyst wall enhancement in pilocytic astrocytoma: neoplastic or reactive phenomena.
AB  - Cystic pilocytic astrocytomas (CPA) consist of a mural nodule and an accompanying
      cyst, which may prominently enhance on MRI after contrast administration. This
      raises the question whether an enhanced wall represents a tumor and thus should
      be resected together with the solid nodule, as radical tumor surgery is
      associated with better prognosis. Until now, no systematic histopathological
      examinations of cyst walls have been reported in correlation with MRI,
      intraoperative appearance and postoperative clinical and MRI follow-up. We
      present 3 patients with CPAs and brightly enhanced cyst walls on MRI. Because of
      the benign, transparent appearance of the cyst wall intraoperatively, it was
      biopsied but not resected, and only radical removal of the nodule and its
      immediate surroundings was performed. Separate specimens taken from the cyst wall
      showed no tumor. MRI performed annually, up to 48-56 months after surgery showed
      no recurrence of the cyst or the tumor. In such cases of CPA, we suggest that
      enhancement of cyst walls may represent reactive rather than tumoral tissue, and
      may be left intact without risking worse prognosis. Mechanisms leading to cyst
      wall enhancement and the optimal surgical treatment are discussed.

PMID- 10965271
TI  - Surgical treatment of temporal tumors associated with epilepsy in children.
AB  - Seizures are a frequent sign of cerebral supratentorial tumors in children,
      especially when the location of the neoplasm is the temporal lobe. We report a
      series of 37 pediatric patients with temporal epileptogenic tumors. They
      represent 80.4% of children affected by temporal neoplasms, confirming the high
      incidence of seizures when neoplasms are located in this cerebral area. There was
      a slight male predominance. Epilepsy was the first symptom in all the patients of
      our series, as well as the only clinical manifestation present until surgery in
      62% of patients. In the remaining children, hemiparesis, intracranial
      hypertension, psychosocial or neuropsychological disabilities, and delayed
      milestones arose before diagnosis and surgical treatment. The most frequent type
      of seizures was the partial complex (56%), but simple partial or generalized
      fits, as well as more than one type of seizures, were observed. The medial
      temporal structures were those more commonly involved, although seizures were
      observed also in cases where they were spared by tumors located exclusively in
      the temporal neocortex. On histology, most of the tumors showed a benign
      phenotype. Tumor resection was complete in 60% of cases; the excision of the
      tumor was incomplete in subjects whose lesion involved surgically inaccessible
      cerebral regions, as language areas, insular structures, and basal nuclei. As for
      epilepsy, 26 among the 32 long-term survivors can be classified in class I of
      Engel's classification; 4 of them did not receive any antiepileptic treatment.
      Four patients showed a significant reduction in the frequency of their fits. In 2
      subjects, only the frequency of seizures was minimally reduced after tumor
      excision; in both, a partial removal of their tumor was performed. The
      relationship among the results on epilepsy and the extent of surgery removal of
      the tumor, brain tissue removal if any, frequency of seizures in the preoperative
      period and the time interval between the first epileptic manifestation and
      surgery show that the most significant prognostic element predictive of a good
      control of seizures is radical resection of the tumor.

PMID- 10965270
TI  - Benign melanocytic tumor in infancy: discussion on a rare case and review of the
      literature.
AB  - Meningeal melanocytoma is an infrequent neoplasm of the central nervous system
      (CNS), especially in childhood and infancy. It was first described as an entity
      different from pigmented meningiomas and schwannomas in 1972, and few cases have
      been published so far. In this article, a 5-month-old male patient with meningeal
      melanocytoma is presented. This midline lesion was localized in the posterior
      fossa and manifested by hydrocephalus. The entire dural origin and extradural
      growing pattern in addition to the destruction of the adjacent occipital bone
      were the unexpected presentations since these tumors usually tend to locate on
      leptomeninges and to extend into the adjacent neural compartment rather than the
      outside. On the other hand, this case is the only one which had identical lesions
      in both surrenal glands and the left renal capsule, the structures containing
      neural-crest-derived cells outside the CNS. The prognostic criteria, differential
      diagnosis and its embryological aspects are discussed with an extensive review of
      the related existing literature.

PMID- 10965272
TI  - Early vasculopathy following radiation in a child with medulloblastoma.
AB  - A child with severe radiation vasculopathy 15 months following radiation therapy
      for medulloblastoma is reported. The patient underwent surgical resection of a
      posterior fossa medulloblastoma, followed by chemotherapy and radiation therapy.
      He was treated with 55 Gy to the craniospinal axis. Fifteen months later, the
      patient presented with a subacute neurologic deterioration from multiple ischemic
      events that resulted from severe radiation vascular injury. We compare and
      contrast this case to similar case reports in the literature.

PMID- 10965273
TI  - Chemotherapy: low-grade gliomas of the hypothalamus and thalamus.
AB  - Chemotherapy is an increasing component of the management of diencephalic
      gliomas. It can result in tumor shrinkage and significant disease control in some
      patients. However, decisions concerning the institution of treatment should be
      based on the goals of treatment. Factors include: (1) age of the patient; (2)
      whether the child has neurofibromatosis type 1; (3) tumor size and location; (4)
      the potential sequelae of radiotherapy, and (5) the acute and long-term toxicity
      of the chemotherapeutic approach utilized. The erratic natural history of
      diencephalic tumors confounds evaluation of efficacy of the regimen chosen.

PMID- 10965275
TI  - A modified burr-hole method 'galeoduroencephalosynangiosis' in a young child with
      moyamoya disease. A preliminary report and surgical technique.
AB  - We performed combined indirect surgical procedures using
      encephaloduroarteriomyosynangiosis and a burr-hole method according to
      descriptions by Suzuki et al. and Kawaguchi et al. with some modifications in a 4
      year-old child with moyamoya disease. Transient ischemic attacks on both sides
      completely disappeared within 1 month and never occurred during 2.5 years follow
      up period. This surgical procedure may have enough value as the first operation
      to prevent ischemic damage in the territories of both the anterior cerebral
      artery and middle cerebral artery in children with moyamoya disease.

PMID- 10965274
TI  - Thalamic and hypothalamic tumors of childhood: endocrine late effects.
AB  - Children who have received chemotherapy and radiation therapy for treatment of
      thalamic/hypothalamic tumors are at risk for late effects, specifically endocrine
      dysfunction. Evaluation of growth and pubertal development, thyroid function and
      integrity of the hypothalamic-pituitary-adrenal axis should be undertaken in a
      prospective manner. Issues of metabolic disturbances such as obesity, altered
      body composition/bone density as well as ultimate fertility also need to be
      addressed by ongoing prospective evaluations.

PMID- 10965276
TI  - Plagiocephaly.

PMID- 10965278
TI  - Late shunt infections.

PMID- 10965277
TI  - A massive nasofrontoethmoidal encephalocele: neurological picture.

PMID- 10965279
TI  - Coping styles and psychosomatic problems: are they related?
AB  - A number of recent studies have shown avoidant coping to be related with diverse
      types of somatic and mental pathology. In order to investigate the relevance of
      coping for both psychological and somatic problems in delinquent subjects, 185
      boys from juvenile correction and 96 boys from secondary schools in Arkhangelsk,
      Northern Russia, were assessed by means of the Coping Scale for Children and
      Youth, the Youth Self-Report and the Giessen Subjective Complaints List - youth
      form. The results from the delinquent subjects partly confirmed previous findings
      on the dominant role of behavioural avoidance in the relationships between coping
      styles and both behavior/emotional problems and somatic complaints. Further
      implications of the results are discussed.

PMID- 10965280
TI  - Depressive symptoms and occupational role among female groups: a research in a
      south-east African village.
AB  - BACKGROUND: Although the relationships between social and cultural factors and
      African psychopathology have largely been considered from a theoretical point of
      view, empirical studies are still few and far between. This paper reports the
      results of a mental health survey conducted in the village of Namwera (Malawi,
      South-East Africa) to explore the link between social conditions, in particular
      occupational role, and psychopathology. METHODS: A modified version of the Self
      Reporting Questionnaire translated into Chichewa language was administered to 161
      women (23 dressmakers, 46 nurses, 92 housewives). A Socio-Anamnestic
      Questionnaire and a Clinical Interview were also applied. RESULTS: Dressmakers
      and housewives appeared more at risk of psychological suffering than nurses.
      Psychosomatic symptoms are more frequent among housewives, while dressmakers show
      more typical depressive symptoms, including suicidal thoughts and self-blame.
      CONCLUSIONS: Data confirm that also in an African context, some social factors
      are related to depression among female groups.

PMID- 10965281
TI  - Can verbalization remedy the theory of mind deficit in schizophrenia?
AB  - Several studies provide convincing evidence of a specific deficit in the theory
      of mind (ToM) in some patients with schizophrenia. This ToM deficit consists of
      an inability to attribute relevant mental states to others, and studies suggest
      it has to be regarded as functional and remediable through the use of reinforced
      context processing. To investigate this, the present study compares the
      performances of 25 schizophrenics and 25 matched controls in a task exploring ToM
      before and after the introduction of verbal material into the task, initially
      conceived as nonverbal. All the controls and half of the schizophrenic subjects
      who did not initially perform at the best level remediated with verbalization,
      while 9 of the schizophrenics exhibited no remediation. These poor performers are
      characterized by a longer duration of illness. The cognitive plasticity and the
      characteristics of patients who do/do not remediate are discussed in the light of
      findings obtained with the Wisconsin Card Sorting Test. The clinical implication
      of these results is important since they suggest that some patients would benefit
      from cognitive rehabilitation in terms of their ability to attribute relevant
      mental states to others.

PMID- 10965282
TI  - Clinical models of schizophrenia: a critical approach to competing conceptions.
AB  - Clinical and etiopathological heterogeneity in schizophrenia has been recognized
      long ago. The main hypothesis held in this report is that as long as we are not
      able to disentangle the heterogeneity question at the clinical level, it is not
      likely that heterogeneity at the etiological and pathophysiological levels may be
      solved. While the description of symptoms and signs of schizophrenia has remained
      mainly unchanged over the years, the way in which authors have articulated the
      varied phenomenological manifestations has been very unequal, thus rendering
      different views of schizophrenia across periods and countries. We still lack a
      global and comprehensive model to understand clinical heterogeneity in
      schizophrenia. In absence of compelling evidence for supporting either a
      categorical or a dimensional view, it is necessary to integrate and empirically
      compare competing approaches. The use of a polydiagnostic approach on the one
      hand, and a multidimensional approach on the other (the polydiagnostic
      multidimensional paradigm), seems to be a promising strategy to better understand
      the heterogeneity of schizophrenia.

PMID- 10965283
TI  - Correlates of symptom dimensions in schizophrenia obtained with the Spanish
      version of the Manchester scale.
AB  - In the last decade, a significant number of studies have been published which
      suggest a multifactorial psychopathological structure in schizophrenia. Seventy
      eight acute and chronic schizophrenic patients diagnosed in accordance with DSM
      III-R criteria were studied with the Manchester Scale, Premorbid Adjustment
      Scale, Family History-RDC Interview, Digit Span, Mini-Mental State and
      computerized tomography (CT). A factorial analysis of the symptoms as recorded
      with the Spanish version of the Manchester Scale was carried out. Three factors
      ('positive', 'negative' and 'disorganization') accounted for 79% of the total
      variance. Poor premorbid adjustment was associated with high scores for the
      'positive' dimension. The 'disorganization' dimension was significantly
      associated with lower scores in the Mini-Mental and attention test than the rest.
      However, CT did not differentiate between these symptom dimensions. This study of
      a sample of mostly outpatients corroborates the hypothesis of three clinical
      dimensions in schizophrenia.

PMID- 10965284
TI  - Comparison of assessment of personality disorder by patients and informants.
AB  - The present study evaluated the pathology of personality disorder in a group of 8
      nonpatient volunteers and 32 psychiatric in- and outpatients, most of them
      suffering from substance abuse disorder. The patient self-reports were compared
      with the reports by 2 informants for each proband. All probands and informants
      completed the Structured Interview for DSM-III-R Axis II Personality
      Questionnaire. Patient self-reports and informant reports yielded the same number
      of diagnoses. The diagnostic agreement between the three sets of data was
      generally poor; however, the concordance was slightly better between both groups
      of informants than between patients and informants: Median kappa were 0.13 for
      patients versus parents, 0.14 for patients versus brothers/sisters and 0.29 for
      parents versus brothers/sisters. Patient and informant evaluations represent two
      different assessment approaches of the personality, and a complete agreement is
      not to be expected.

PMID- 10965285
TI  - A case of comorbidity between panic disorder and photosensitive epilepsy.
AB  - Panic disorder and epilepsy usually are distinct entities which require different
      and specific therapeutic strategies. While anticonvulsant medication is the
      treatment of choice for seizure disorders, behavioral methods have proven to be
      effective in panic disorder. We here report a case of comorbidity between panic
      disorder and photosensitive epilepsy. Special attention is given to the different
      symptomatic presentations of the disorders, because a thorough knowledge of both
      disorders may save unnecessary diagnostic procedures. Therefore, the necessity of
      taking a careful patient's history is underlined. Furthermore the different
      possible relationship between panic disorder and epilepsy are discussed.

PMID- 10965286
TI  - Schizophrenia and common sense: study of 3 single cases.
AB  - There is new interest in subjective experiences of schizophrenia. This kind of
      analysis emphasizes the subjective stories of patients, and the methods do not
      pretend to have the objectivity of science. However, the plausibility and the
      empathetic resonance of the single case may bring subjective confirmation to the
      validity of an insight and indicate new directions of research. Following this
      line, the authors present a study of 3 single cases of 'reflexive' residual type
      of schizophrenia. The methods for selecting the cases and the philosophical
      groundings of the concept of 'reflexive schizophrenia' are explained. The
      analysis of the single cases revealed that (1) schizophrenic persons' cognitive
      deficit is related to the constitution of common sense; (2) some schizophrenics
      cope with the cognitive deficit by creating a theoretical corpus of axioms
      stemming from common sense, namely the 'axioms of everyday life'; (3) this
      mechanism of coping is described as an inflexible attachment to 'axioms of
      everydayness', and (4) this attachment to common sense releases the patient from
      all personal investment of self in the process of anchoring in the living world
      and, on this basis, allows a relatively solid, although distant, attachment to
      reality. The nature of deficit in schizophrenia is also discussed by confronting
      the phenomenological point of view and the neuropsychological, that is the so
      called 'theory of mind'.

PMID- 10965287
TI  - Reducing relapse in depressed outpatients with atypical features: a pilot study.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) and atypical features
      have reactive mood plus at least two symptoms: hypersomnia, hyperphagia, leaden
      paralysis or a lifetime sensitivity to rejection. These patients respond to
      cognitive therapy (CT) or phenelzine (PHZ) significantly more than pill placebo
      (PBO). The purpose of this report is to motivate research on tolerable
      continuation phase treatment designed to reduce the significant risk of relapse
      and recurrence which depressed patients with atypical features face. METHODS:
      Outpatients with DSM-III-R MDD and atypical features who responded to acute-phase
      CT, clinical management plus PHZ or PBO (n = 31) were randomized to continue or
      discontinue treatment for 8 months and participate in 16 months or treatment-free
      follow-up. RESULTS: A log-rank test showed that the relapse and recurrence-free
      survival over the 24 months after the acute phase was significantly greater for
      the responders who continued treatment than for those who discontinued treatment.
      Kaplan-Meier estimates of relapse and recurrence were significantly higher for
      patients whose treatment was discontinued than for those whose treatment
      continued (83 vs 49% based on unblinded ratings of the Research Diagnostic
      Criteria for MDD or of self/other referral for treatment of depressive symptoms).
      CONCLUSIONS: We note several important limitations of the design and analysis of
      these pilot data. We hypothesize that not only pharmacotherapy, but also CT used
      as a continuation phase treatment may reduce relapse in this population. This
      hypothesis warrants rigorous evaluation in samples of outpatients with MDD and
      atypical features that are large enough to allow comparative tests.

PMID- 10965288
TI  - Cognitive therapy by allocation versus cognitive therapy by preference in the
      treatment of panic disorder.
AB  - BACKGROUND: Little is known about the influence of preference for a given therapy
      or preference against a modality of treatment on the outcome of that treatment.
      Results so far have been conflicting. The primary aim of this study was to
      investigate possible differences in outcome between panic disorder patients
      treated with preferred cognitive therapy and patients treated by randomization
      with the same intervention. METHODS: A 12-week study comparing 35 patients
      treated by allocation with 31 patients treated by preference. RESULTS: There were
      no differences at pretest between the two conditions on demographic or outcome
      measures. Outcome was assessed with measurements rating the panic frequency and
      severity of agoraphobia, general anxiety and depression. Both conditions improved
      significantly on nearly all ratings. There were no significant differences
      demonstrable between the two conditions on any of the outcome measures.
      CONCLUSION: Preference for a given therapy is not a powerful moderator of effect
      in the psychological treatment of panic disorder.

PMID- 10965289
TI  - Comorbidity, smoking behavior and treatment outcome.
AB  - BACKGROUND: A sizeable sector of the population continues to smoke cigarettes
      despite our efforts to prevent and treat this addiction. We explored the
      relationships between lifetime comorbidity, psychiatric symptomatology, smoking
      behavior and treatment outcome to better understand vulnerability to smoking and
      treatment response. METHODS: One hundred and twenty smokers at two sites were
      enrolled in a multicenter, double-blind, randomized, 10-week smoking cessation
      trial with fluoxetine and behavioral treatment. The Structured Clinical Interview
      for DSM-III-R and Hamilton Depression Rating Scale were administered prior to
      treatment initiation. Self-report measures were used to assess psychiatric
      symptoms throughout treatment and during a 6-month follow-up period. RESULTS:
      Overall 62.3% of our sample were diagnosed with a lifetime mood, anxiety or
      substance use disorder despite stringent study exclusion criteria. Lifetime
      comorbidity was shown to be related to higher smoking rates and nicotine
      dependence, depressed mood and greater self-report of anxiety and stress.
      Lifetime comorbidity, however, alone or in combination with treatment condition,
      failed to predict treatment outcome (at posttreatment or follow-up). Baseline
      depression scores (Beck Depression Inventory, BDI) were related to treatment
      outcome only for smokers without a positive history of any psychiatric disorder
      or depression, with lower BDI scores more frequent in those who were abstinent.
      CONCLUSIONS: High prevalence rates of lifetime psychiatric illness and substance
      use disorders are reported for chronic smokers. Subsyndromal psychiatric symptoms
      may play a role in smoking behavior in combination with diagnosable disorders.
      Clinicians need to carefully assess both psychiatric diagnoses and symptoms in
      chronic smokers to optimize patient-treatment matching.

PMID- 10965290
TI  - The prevalence and differential diagnosis of subclinical depressive syndromes in
      inpatients 60 years and older.
AB  - BACKGROUND: Depressive syndromes that do not comply with the diagnostic criteria
      for specific depressive disorders are designated as 'subclinical' or
      'subsyndromal' depressive syndromes. Using our own data from a clinical study,
      this paper outlines the significance of subclinical depressive syndromes and
      demonstrates the problems of differentiating between depressive and subclinical
      depression (SD) syndromes and organic mood disorders especially in an elderly
      population with medical comorbidity. METHODS: Two hundred and sixty-two patients
      aged 60 years and older in a general hospital were investigated, using a clinical
      psychiatric interview, expert ratings and self-report scales after extensive
      internal medical diagnostic evaluation. RESULTS: When, without further
      differentiation as to their origin, all symptoms required by symptom checklists
      according to ICD-10 were considered for the diagnosis of major depression (MD),
      35.5% of the study participants fulfilled the diagnostic criteria. After
      differentiating for etiology of symptoms, MD was found in only 14.1%, SD was
      diagnosed in 17.6% and organic mood disorder in 12.2% of the study participants.
      In another 41 patients (15.6%), symptoms of depression not fulfilling ICD-10
      criteria were classified as being of organic or drug-induced origin. SD patients
      were in a mean position between nondepressive and depressive patients with regard
      to social isolation and physical impairment; women were overrepresented in the
      depressive and subdepressive groups. CONCLUSIONS: SD and organic mood disorder
      are common and helpful diagnostic categories in the elderly. The results show
      that in old age there is substantial danger of confounding MD, SD and organic
      mood disorder, thus leading to erroneously high prevalence rates of MD and
      underestimations of organic mood disorder if depressive symptoms are recorded
      only by self-report scales or a symptom checklist. Both internal and
      psychosomatic-psychotherapeutic competence as well as a liaison service in
      general hospitals are necessary for the differential diagnosis of MD, SD and
      organic mood disorder in the elderly with medical comorbidity.

PMID- 10965291
TI  - Psychosocial indexes and cardiovascular risk factors in a community sample.
AB  - BACKGROUND: Psychosocial characteristics might contribute to a more comprehensive
      understanding of cardiovascular disease as it is increasingly recognised that
      biomedical risk factors do not fully explain its dynamics. This study aimed to
      describe psychometric indexes in a Portuguese community sample relating them to
      known cardiovascular disease risk factors. METHODS: Anthropometric, blood
      pressure, serum measurements and information on demographic, social, medical and
      behavioural characteristics were obtained for 215 women and 156 men. Self
      administered questionnaires were used for the psychometric evaluation (Bortner
      scale, Beck Depression Inventory, Hopkins Symptom Distress Checklist 90-Revised,
      Psychological General Well-Being and the Nottingham Health Profile, NHP).
      RESULTS: There were significant differences according to gender regarding almost
      every psychometric dimension assessed. After adjusting for the presence of
      different biomedical risk factors, significant decreasing mean behaviour pattern
      scores were found with increasing age. Mean depression scores were significantly
      higher in women and in individuals with lower educational level. As to general
      psychological well-being, the highest scores were obtained for men and
      individuals with higher educational level. For the assessed dimensions of quality
      of life, as well as indexes of psychopathology, men scored better than women. No
      significant differences in mean scores of behaviour pattern, depression,
      psychological general well-being and dimensions of NHP were found according to
      the presence of an increasing number of cardiovascular risk factors. CONCLUSIONS:
      The study shows that the clustering of multiple biomedical risk factors does not
      result in additive deleterious psychological effects and that psychometric
      indexes are mainly dependent on gender and education, common confounders in most
      studies evaluating cardiovascular risk factors.

PMID- 10965292
TI  - Stress-response in male partners of women submitted to in vitro fertilization and
      embryo transfer.
AB  - BACKGROUND: In a previous work, we have reported the relationship between women
      and the outcome of in vitro fertilization and embryo transfer (IVF-ET). The goal
      of the present work is to evaluate the association between vulnerability to
      stress and treatment outcome in male partners of couples submitted to IVF-ET.
      METHODS: The day of semen collection at the Assisted Reproduction Unit of the
      Department of Obstetrics and Gynecology, University of Modena, 45 subjects were
      submitted to Stroop Color Word Conflict, a task measuring the ability to cope
      with a cognitive stressor, involving the attentional and sympathoadrenal system.
      Systolic and diastolic blood pressure, as well as heart rate (HR), were measured
      at baseline, during the test and 10 min after the end of testing. The evidence of
      pregnancy (betahCG >250 mIU/ml 12 days after ET) is the main outcome measure; the
      couples were classed in either a 'success' or a 'failure' group. RESULTS:
      Thirteen couples became pregnant. Pregnancy progressed until term in 6 cases,
      while 7 cases showed only a preclinical evidence of pregnancy. Age, education,
      causes and duration of infertility were similar in the success and failure
      groups. No difference was found in the number and motility of spermatozoa both at
      baseline and after capacitation (a technique improving sperm motility). Moreover,
      the success group showed a higher number of both fertilized oocytes and embryos
      transferred compared with the failure group. The area under the curve of the
      cardiovascular parameters was calculated. The failure group showed a higher value
      for HR (50.6 +/- 36.7 of percent total change) than the success group (31.8 +/-
      16.9; p = 0.006). CONCLUSIONS: The cardiovascular response to stress is a good
      correlate of success in infertile males submitted to the IVF-ET program.

PMID- 10965293
TI  - Female depression before and after menopause.
AB  - BACKGROUND: There is no clear association between menopause and depression. Aim
      of the study was to compare female depression with onset before menopause with
      female depression with onset after menopause, to find out if endocrinological
      changes had an impact on depression. METHODS: Five hundred and twelve consecutive
      unipolar and bipolar I/II depressed outpatients were interviewed with the
      Structured Clinical Interview for DSM-IV, the Montgomery-Asberg Depression Rating
      Scale and the Global Assessment of Functioning scale. Patients were divided into
      patients with depression/mania onset before 40 and after 40. RESULTS: Female
      depression with onset after 40 had a significantly shorter duration of illness,
      fewer recurrences, fewer patients with atypical features, fewer bipolar II
      patients and more unipolar patients than female depression with onset before 40.
      Male depression with onset after 40 had a significantly shorter duration of
      illness and fewer patients with atypical features than male depression with onset
      before 40. CONCLUSIONS: Some features were common to both female and male
      depression with onset after 40. Female depression with onset after 40 had
      significantly more unipolar and fewer bipolar II patients, than female depression
      with onset before 40. Different frequency of unipolar and bipolar II patients
      suggests that the biology of depression in menopause women may be different from
      that of women not in menopause, and from that of male depression with onset after
      40. Differences may be related to menopause.

PMID- 10965294
TI  - Urological aspects of female sexual dysfunction.
AB  - The aetiology of male sexual dysfunction has been extensively investigated over
      the past few decades. This has led to the development of effective treatment for
      this common problem. However, to date, female sexual dysfunction has received
      very little attention, particularly from a urological point of view. In this
      review, we discuss the anatomy and physiology of the female sexual organs as well
      as the aetiological factors that are associated with female sexual dysfunction.
      An improved awareness and understanding of this subject may, in the future,
      enable us to address female sexual dysfunction more appropriately and develop
      suitable treatment.

PMID- 10965295
TI  - Politano-leadbetter ureteroneocystostomy. A 30-year experience.
AB  - PURPOSE: We evaluated the results and complications of children with reflux
      treated with the Politano-Leadbetter ureteroneocystostomy. In particular, we
      evaluated pre- and postoperative renal parenchymal scarring and the late
      development of hypertension. MATERIALS AND METHODS: From 1965 through 1996, 666
      children (814 renal units) were reimplanted by nine urologists. The average
      postoperative evaluation was 10.3 years, and 68.8% of all patiens were evaluable
      10 years after surgery. RESULTS: Postoperative complications occurred in 7.8% and
      consisted of small bowel serosal injury (0.3%), vesicocutaneous fistula (0.4%)
      and retrovesical hematoma (0.3%). Persistent reflux was the most common
      postoperative complication (5.6%) and was found to occur in higher grades of
      vesicorenal reflux. Ureteral stricture and hydronephrosis were seen in 1.2% of
      children, and was corrected with a secondary reimplantation. Late stricture
      occurred in all but 1 patient (0.2%). Renal parenchymal scarring was found in
      21.2% of patients preoperatively, and this increased over time postoperatively to
      27.7%. In 8.7% of these patients, hypertension developed between the 6th and 17th
      postoperative year. In 6.1%, nephrectomy was carried out, which normalized blood
      pressures in 87. 9% of these 30 patients. CONCLUSIONS: The Politano-Leadbetter
      ureteroneocystostomy was successful in 93.6% of all 814 renal units surgically
      treated. The operation is safe, but can be associated with late development of
      hypertension despite correction of the reflux.

PMID- 10965296
TI  - Testicular sperm extraction combined with cryopreservation of testicular tissue
      in the treatment of azoospermia.
AB  - BACKGROUND: The aim of the present study was to verify the feasibility of
      cryopreserving testicular tissue during the first diagnostic biopsy and then
      using thawed sperm to inseminate the partner's oocytes. The expected advantages
      are: (i) minimal risk of not having spermatozoa available at the time of
      intracytoplasmic sperm injection; (ii) no repeated surgical interventions, and
      (iii) programming the treatment cycle at the couple's convenience. MATERIALS AND
      METHODS: Between May 1996 and May 1998, 64 azoospermic patients underwent
      investigative testicular biopsy combined with cryopreservation of spermatozoa
      which were retrieved in a simultaneously examined fresh sample. Testicular tissue
      cryopreservation was carried out in 43 cases (67%) for later intracytoplasmic
      sperm injection attempts. RESULTS: In all, 23 couples underwent 26 assisted
      conception cycles; the fertilization rate was 64% with spermatozoa (139/218, 24
      cycles), 40% with round spermatids (2/5, 1 cycle), and 69% with elongated
      spermatids (9/13, 1 cycle). The embryo cleavage rate was 84%. The mean number of
      embryos replaced in 24 patients was 2.7 +/- 0.7. In 2 cases, embryo quality was
      very poor, and they were not transferred to the patients. Eight clinical
      pregnancies resulted (35%/patient and 33%/transferred cycle) with an implantation
      rate of 14.1%; 2 patients have already delivered and 6 pregnancies are ongoing
      normally. CONCLUSIONS: Testicular tissue cryopreservation during the first
      diagnostic biopsy is an alternative to repeated surgical interventions. Patients
      can initiate an ovarian stimulation cycle, confident of having spermatozoa
      available. Moreover, since only one straw is routinely used for each
      intracytoplasmic sperm injection cycle, the frozen tissue remains as a sperm
      source for multiple attempts.

PMID- 10965297
TI  - Cytokines accumulated in acquired renal cysts in long-term hemodialysis patients.
AB  - BACKGROUND: Cytokines play a pivotal role in growth, differentiation, and
      apoptosis. In this study, we measured cytokine content in the renal cyst fluid of
      patients with acquired cystic disease of the kidney (ACDK) in order to elucidate
      the possibility that cytokines are related to the development of ACDK. PATIENTS
      AND METHODS: All or some of 15 cytokines, IL-1a, -1b, -2, -4, -5, -6, -8, -10,
      IFN-alpha, -gamma, G-, M-, GM-CSF, TNF-alpha, and vascular endothelial growth
      factor (VEGF) were analyzed in cyst fluid and serum of 12 patients on
      hemodialysis (HD) including 8 with ACDK and 8 with normally functioning kidneys
      by sandwich enzyme-linked immunosorbent assay. RESULTS: Out of these cytokines,
      only IL-6, -8, M-CSF, and VEGF were detected in the cyst fluid of patients with
      ACDK. Moreover, IL-6, -8, and VEGF showed significantly higher concentrations in
      the cyst fluid than in the blood (194.9 +/- 90.9 vs. 0.0 +/- 0.0 pg/ml, 2,377. 5
      +/- 602.9 vs. 0.0 +/- 0.0 pg/ml, 5,167.8 +/- 1,316.9 vs. 41.1 +/- 14.7 pg/ml,
      respectively), while M-CSF showed comparable concentrations in the cyst fluid
      with those in the blood (3,519.4 +/- 730.0 vs. 3,250.3 +/- 319.1 pg/ml, p =
      0.69). Additionally, IL-6, -8, and VEGF accumulated more abundantly in the cyst
      fluid of patients with ACDK than in that of patients with other cystic
      nephropathies including ADPKD patients on HD (194.9 +/- 90.0 vs. 4.6 +/- 3.2
      pg/ml, 2,377.5 +/- 602.9 vs. 76.8 +/- 46.5 pg/ml, 5,167.8 +/- 1,316.9 vs. 131.1
      +/- 63.1 pg/ml, respectively). However, there was no significant correlation
      between the intracystic concentrations of these cytokines and the corresponding
      cyst diameters. CONCLUSION: These results showed that in ACDK patients a local
      environment exists in which production or accumulation of certain cytokines is
      selectively enhanced compared with patients with other cystic nephropathies. They
      imply that these cytokines are closely related to pathogenesis particular to
      ACDK.

PMID- 10965298
TI  - Hormonal sensitivity following endocrine withdrawal in hormone-refractory
      prostate cancer.
AB  - BACKGROUND: Prostate cancer is proposed to be classified according to hormonal
      sensitivity. The purpose of this study is to examine hormonal sensitivity of the
      patient with refractory prostate cancer subsequent to primary hormonal therapy.
      METHODS: Sixteen patients with refractory prostate cancer subsequent to primary
      combination hormonal therapy were enrolled in this study. All 16 patients with
      progressive disease after elimination of oral hormonal agents or after response
      following hormonal withdrawal received dexamethasone (DXM) (initially 1.5 or 1.0
      mg, then tapered to 0.5 mg) orally not only for the purpose of second-line
      hormonal therapy but also as an indicator of hormonal sensitivity. RESULTS:
      Overall, 4 patients showed a prostate-specific antigen (PSA) decrease of >50%
      from baseline on discontinuation of hormonal agents, while another 7 patients
      showed a PSA decrease of <50%. Five patients showed PSA level was progressed
      after the withdrawal. In all patients with PSA values that decline not only >50%
      but also <50% following oral endocrine withdrawal, the fall in PSA values had
      been >50% following DXM administration. However, the PSA value in the patients
      with PSA progression following the oral endocrine withdrawal kept rising after
      DXM administration. CONCLUSIONS: The findings in this study would just suggest a
      possible relationship between DXM sensitivity and the response to endocrine
      withdrawal. The patients whose PSA values decline following oral endocrine
      withdrawal may maintain hormonal sensitivity.

PMID- 10965299
TI  - Lipid peroxidation and the expressional regulation of the heat-shock response
      during ischemia-reperfusion of rat kidney.
AB  - Because of the continuing shortage of donor organs, 'marginal kidneys' are
      increasingly being used. The purpose of our experiments was to characterize the
      extent of lipid peroxidation after ischemia-reperfusion (IR) injury in rat
      kidney, to analyze the expressional regulation of the heat-shock response and now
      to discuss the clinical application of these results. After ischemia, xanthine
      oxidase (XO) is thought to be the main oxygen radical-generating system and
      malondialdehyde (MDA) is considered to be a marker of LPO. In young rats (10
      weeks) a unilateral warm ischemia of 40 and 60 min duration with subsequent
      reperfusion up to 1 h was conducted. Beside the 'footprints' of oxidative stress,
      the cytosolic antioxidative capacity, expressed as superoxide anion (SOA)
      scavenging capacity, was investigated. There was only a moderate and transient
      increase of renal MDA 5 and 10 min after the onset of reoxygenation (133.57/70.67
      and 97.84/91.57 vs. 49.47 nmol/g wet weight (ww) in preischemic controls). ATP
      breakdown (to 83/65 from 2,947 nmol/g ww) with consecutive accumulation of
      hypoxanthine (up to 1,105 nmol/g ww) at the end of the ischemic period and the
      subsequent rapid decline of hypoxanthine by XO during reperfusion were used for
      an assessment of the SOA-generating capacity of these kidneys. Only 1/25-1/50 of
      the kidney cytosol was able to scavenge the whole amount of SOA generated by the
      total XO activity of rat kidney. Thus, it could be analytically and
      stoichiometrically shown that after IR there is only a moderate oxidative stress
      in kidneys of young rats; this is due to their high SOA-scavenging capacity
      compared to their SOA-generating ability. We investigated the time course of
      HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in renal
      cortex after different periods of unilateral warm renal ischemia (10-60 min) and
      reperfusion (up to 60 min) in 10-week-old male Wistar rats, since IR is known to
      cause induction of both genes. Immediately after ischemia there was a significant
      induction of both HSP70i genes. While HSP70-1 expression constantly increased (up
      to 4-fold) during reperfusion, even to a higher extent with prolongation of
      ischemia, HSP70-2 mRNA - generally being expressed on a far lower level than
      HSP70-1 mRNA - was strongly induced (3-fold) during reperfusion only after brief
      periods (10 min) of ischemia. Cellular ATP levels rapidly dropped down to 5% with
      ischemia and the pattern of recovery during reperfusion significantly depended on
      the duration of the ischemic period thus showing a good relation to the heat
      shock (protein) gene expression. We conclude that the HSP70-2 is the more
      sensitive gene with a lower threshold activation by mild injury, while the HSP70
      1 gene mediates the big response of HSP induction after severe injury. Thus, the
      measurement of the cytosolic antioxidative capacity and the differential
      expression of HSP70-1 and -2 mRNA could be promising clinical tools to assess the
      donor viability.

PMID- 10965300
TI  - Bladder dysfunction due to Behcet's disease.
AB  - Behcet's disease is a multiple disorder in which urogenital involvement mainly
      consists of genital aphthous ulcers, epididymitis, urethritis and recurrent
      cystitis. We report 2 cases of neurogenic bladder due to Behcet's disease. Both
      cases showed detrusor hyperreflexia and detrusor-sphincter dyssynergia. One case
      has been managed by twice-daily intravesical oxybutynin treatment (5 mg/10 ml)
      and clean intermittent catheterization (CIC) 7 times/day, and the other case has
      been managed by CIC 6 times/day.

PMID- 10965301
TI  - Fatal basilar artery thrombosis after chemotherapy for testicular cancer.
AB  - We report a 31-year-old patient with a pT3N2M1 seminoma who received cisplatin
      based chemotherapy. During the second course of chemotherapy, the patient
      suffered a thrombosis of the basilar artery. He died 14 h after hospital
      admission. Cerebrovascular events related to cisplatin-based chemotherapy are
      rare, however, these potentially fatal events should be kept in mind when
      treating patients with testicular cancer.

PMID- 10965302
TI  - Three-dimensional CT scan stone reconstruction for the planning of percutaneous
      surgery in a morbidly obese patient.
AB  - A three-dimensional spiral CT (3D CT) reconstruction of staghorn stones provides
      a precise picture of its extent and branching within the kidney. The author
      reports a case of a large renal staghorn stone in a morbidly obese woman, further
      complicated by malrotation and hypermobility of the kidney. Two-dimensional plain
      CT was unable to provide sufficient information for a safe percutaneous approach.
      This was achieved by means of 3D CT, which also was very helpful during the
      procedure. Although 3D CT should by no means be routinely employed, it is a
      valuable tool for pretreatment decision-making and intraoperative orientation in
      selected cases.

PMID- 10965303
TI  - Solitary fibrous tumour of the kidney.
AB  - Solitary fibrous tumours are relatively rare neoplasms initially described in the
      pleura. Such lesions are now reported in many extrathoracic sites. To our
      knowledge, only 8 cases have been reported in the kidney. All these cases were
      benign. We report a patient with a solitary fibrous tumour of the kidney with
      infiltration of the wall of the renal vein. Microscopic examination showed
      proliferation of spindle cells with a prominent vascular haemangiopericytoma-like
      pattern. Hypercellular areas were admixed with hyalinized collagenous zones. The
      neoplastic cells stained for vimentin and CD34. CD31 was negative. Biologically,
      we did not find any arguments for malignancy: the flow cytometric study showed
      diploid histograms, and immunostaining for p53 was negative.

PMID- 10965304
TI  - Solitary fibrous tumor of the peritoneum found in the prevesical space.
AB  - Solitary fibrous tumors (SFT) are well recognized in the pleura, but their rare
      occurrence at other sites has become appreciated only in recent years. We
      experienced a 68-year-old male patient who presented with frequency of urination
      and difficulty in voiding. Computed tomographic scan revealed a solid and cystic
      mass which measured 12 x 10 cm in the prevesical space. This tumor showed typical
      histopathologic features of SFT, and was immunostained positive for vimentin,
      CD34 and CD99. This is an extremely rare case of SFT arising from the parietal
      peritoneum found in the prevesical space.

PMID- 10965305
TI  - Recurrent aggressive angiomyxoma of the urinary bladder. Case report and review
      of the literature.
AB  - Aggressive angiomyxoma is a rare neoplasm which predominantly involves the female
      pelvis and perineum. Forty-four cases have been reported in the world literature,
      including 10 cases in men. To the best of our knowledge, the first case of
      recurrent aggressive angiomyxoma of the urinary bladder is presented here.
      Operative management, radiologic features and pathological findings are
      discussed.

PMID- 10965306
TI  - Inverted papilloma arising in a juvenile.
AB  - A 15-year-old man presented with painless, gross hematuria. Excretory pyelography
      showed a filling defect in the bladder and ultrasonography revealed a solitary
      bladder tumor. Cystoscopy showed a solitary, papillary tumor on the bladder neck.
      Transurethral resection was then performed and histological examination showed an
      inverted papilloma. In addition, the expression of proliferative cellular nuclear
      antigen and p53 in the surgical specimen were 37.1 and 0%, respectively. Since an
      inverted papilloma arising during the first two decades of life is quite rare, we
      herein report the above case and review previous reports.

PMID- 10965307
TI  - The role of surrogate outcome measures in evaluating medical devices.

PMID- 10965308
TI  - Laparoscopic detection and resection of insulinomas.
AB  - BACKGROUND: Laparoscopic ultrasonography as a diagnostic tool for the
      localization of islet cell tumors has been described before, but few reports on
      laparoscopic resection of insulinomas exist. We retrospectively reviewed the
      results of our experience with laparoscopic detection and the resection of
      insulinomas to determine its feasibility. METHODS: Between February 1996 and
      February 1999, 10 patients underwent operation for organic hyperinsulinism at our
      institution. Patient and clinical characteristics were studied retrospectively.
      Laparoscopic ultrasonography was performed to localize the insulinoma and then
      laparoscopic resection was performed. RESULTS: Eight women and 2 men underwent
      operation for hyperinsulinism. In 6 patients the insulinoma could be resected
      laparoscopically, either by enucleation (5 patients) or by resection of the
      pancreatic tail (1 patient). Four procedures were converted to laparotomy for the
      proximate location of the insulinoma to the portal vein or pancreatic duct (3
      procedures) and failure to identify the insulinoma (1 procedure). The overall
      success rate of preoperative localization of an insulinoma with the use of
      various imaging techniques was 60% (6/10 patients). Laparoscopic ultrasonography
      could identify an insulinoma in 90% of the patients (9/10 patients). The median
      hospital stay was 7 days. CONCLUSIONS: Laparoscopic ultrasonography followed by
      laparoscopic removal of the insulinoma in patients with clinically manifested
      hyperinsulinism is a feasible and safe technique with low morbidity and fast
      postoperative recovery. Preoperative localization studies appear of limited
      value.

PMID- 10965309
TI  - Severe dysphagia after laparoscopic fundoplication: usefulness of barium meal
      examination to identify causes other than tight fundoplication--a prospective
      study.
AB  - Background. The aim of this study was to determine the results of a barium meal
      examination after laparoscopic wrap in symptomatic patients (SPs) with no upper
      endoscopic anomalies and no increase in inferior esophageal sphincter pressure
      (SPs). Radiologic results were compared with results from patients with no
      symptoms (ASPs) and were compared with the surgical findings in patients who
      underwent reoperation. Methods. Twenty SPs were included 27 +/- 6 months after a
      total wrap (n = 13 Nissen procedures) or a posterior wrap (n = 7 Toupet
      procedures) performed in several hospitals in Haute Normandie. All patients had
      severe symptomatic dysphagia with epigastric pain (n = 18 patients) and/or marked
      weight loss (n = 16 patients). Control subjects were 31 consecutive ASPs within
      our center who were prospectively included 4 +/- 1 months after a Nissen (n = 6
      patients) or a Toupet (n = 25 patients) procedure. A barium meal examination was
      performed in all patients and interpreted by 3 independent observers who knew
      that the patients had undergone a wrap but who did not know whether the patients
      had symptoms. Fifteen of the 20 SPs underwent a second operation. Results. Barium
      meal examination was more often abnormal in SPs than in ASPs (17/20 vs 4/31
      patients; P <.001), whichever the type of wrap. Two abnormal radiologic results
      were observed in both groups: an esophageal barium level and an esogastric
      plication. Only a high barium level in the esophagus was more frequently observed
      in SPs than in ASPs (P <.05). Three radiologic results were specifically observed
      in SPs: a long cardial narrowing beginning above the wrap, a mediogastric
      plication, and a gastric volvulus. A comparison of radiologic anomalies and
      surgical findings showed that (1) a radiologic long cardial narrowing was
      explained by fibrotic stenosis of the muscular esophageal hiatus (n = 6
      patients), (2) a mediogastric plication (n = 4 patients) was due to gastric
      volvulus (n = 3 patient) or to gastric wrap (n = 1 patient), and (3) results of
      volvulus (n = 5 patients) indicated a gastric volvulus. Additional surgical
      procedures resulted in the disappearance of symptoms in 13 of 15 patients.
      Conclusions. After laparoscopic fundoplication when upper endoscopy and
      esophageal manometry are normal, results of a barium meal examination can explain
      the cause of dysphagia in almost all patients. Three radiologic results were
      specific for SPs and indicated major morphologic disturbances that could not be
      treated by endoscopic dilation but that could be treated by additional surgical
      procedures.

PMID- 10965311
TI  - Reply

PMID- 10965310
TI  - Endothelin receptor blockade in severe acute pancreatitis leads to systemic
      enhancement of microcirculation, stabilization of capillary permeability, and
      improved survival rates.
AB  - BACKGROUND: We previously demonstrated that therapy with a new endothelin A
      receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute
      pancreatitis (AP) in the rat without attenuating local signs of disease severity
      (intrapancreatic protease activation, acinar cell necrosis). This raised the
      question as to why ET-RA was so effective. The purpose of this study was to
      assess the effect of ET-RA on microcirculation (particularly capillary
      permeability) within and outside of the pancreas on intravascular fluid loss and
      extravascular fluid sequestration and on distant organ function. METHODS: Severe
      AP was induced in rats by standardized intraductal bile acid infusion and
      cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30
      rats) after the onset of AP, animals randomly received either the ET-RA (LU
      135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate).
      At 24 hours, animals were relaparotomized for intravital microscopic
      determination of capillary blood flow, leukocyte rolling, and capillary
      permeability in the pancreas and colon. Further monitoring included
      cardiorespiratory and renal parameters, hematocrit levels and quantification of
      ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of
      sham-operated healthy animals (n = 6 animals each) that had been treated
      according to the same protocol served as control animals. RESULTS: ET-RA
      treatment that was started 6 hours after AP-induction significantly decreased
      hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment),
      reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and
      improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory
      parameters. Moreover, all microcirculatory parameters were improved; in
      particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in
      the colon). These beneficial effects were also seen when therapy was delayed
      until 12 hours after AP induction. Pancreatic necrosis was not significantly
      reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in
      saline solution-treated control animals (P <.05). In healthy animals ET-RA did
      not significantly alter the target parameters, except for a reduction of
      capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation
      and stabilized capillary permeability in ET-RA-treated animals together with
      reduced intravascular fluid loss and extravascular fluid sequestration and
      improved renal and pulmonary function (1) may explain improved survival in this
      model, (2) support the hypothesis that systemic disease sequelae significantly
      contribute to outcome in AP, and (3) suggest that ET-RA may be a promising
      therapeutic tool in AP because it counteracts microcirculatory disorders that
      contribute to pancreatitis-associated organ dysfunction even when therapy is
      delayed to a point at which pancreatic injury may no longer be influenced.

PMID- 10965312
TI  - Vascular invasion and potential for tumor angiogenesis and metastasis in gastric
      carcinoma.
AB  - BACKGROUND: Hematogenous metastasis occurs when cancer cells released from the
      primary site enter blood vessels and are transported to distant organs, where
      they attach and proliferate. Angiogenesis is essential for tumor growth and
      metastasis and depends on the production of angiogenic factors by tumor cells.
      METHODS: We analyzed data on 1184 Japanese adult men and women with gastric
      cancer with respect to the relation between vascular invasion and the potential
      for tumor angiogenesis and metastasis. All these patients were treated from 1976
      to 1995 in the Department of Surgery II, Kyushu University. In 300 patients, the
      expression of vascular endothelial growth factor (VEGF) and p53 protein in tumor
      tissues was examined by using an immunohistochemical staining method or Northern
      blotting or both. Intratumoral microvessels were stained with anti-CD31
      monoclonal antibody. RESULTS: Vascular invasion was evident in 254 patients
      (21.5%), and in these patients lymphatic invasion was more frequent and the rate
      of lymph node metastasis was higher in relation to the extent of vascular
      invasion. The positive findings were directly related to the depth of invasion
      and the presence of lymph node and liver metastasis. Tumor invasive and
      metastatic rates increased in relation to the extent of vascular invasion.
      Expressions of VEGF and p53 protein were higher and microvessel density was more
      prominent in tumor tissues in relation to the extent of vascular invasion. A
      close relation between VEGF and p53 protein expressions was also noted in tumors
      that showed vascular invasion. The expression of VEGF is one of the independent
      risk factors for vascular invasion. The postoperative outcome was poorer in
      patients with vascular invasion in relation to the extent of vascular invasion.
      CONCLUSIONS: Our findings show that gastric cancers with characteristics of
      vascular invasion have greater intratumoral angiogenesis and that VEGF and p53
      overexpression is associated with intratumoral angiogenesis and metastases to
      distant organs.

PMID- 10965313
TI  - Intrahepatic inflow areas of the drainage vein of the gallbladder: analysis by
      angio-CT.
AB  - BACKGROUND: The drainage veins of the gallbladder (cystic veins) are important
      hepatic metastatic routes of gallbladder cancer. We studied the cystic vein
      inflow portions of the intrahepatic vessels by computed tomography during
      angiography (angio-CT). METHODS: The subjects were 27 unoperated pancreatic
      biliary patients. After superselective catheterization of the cystic artery,
      angio-CT was performed, and cystic veins and sinusoidal filling were visualized.
      We identified the cystic vein inflow routes and the vessels they fed. RESULTS: We
      found 72 cystic veins in 26 patients. All cystic veins flowed into the
      intrahepatic portal branches or sinusoids. The cystic veins took either of two
      routes: one into the liver through the hepatic hilum (17 patients, 21 veins),
      taken mainly by the portal branch for subsegment 4a (P4a), the anterior portal
      branch, and the umbilical portion of the portal branch; and the other through the
      hepatic bed (23 patients, 51 veins), taken mainly by S4a sinusoid, S5 sinusoid,
      P4a, and P5. CONCLUSIONS: Angio-CT is useful for detecting the cystic vein inflow
      portions of the intrahepatic vessels. It makes possible identification of areas
      where there is a possibility for micrometastasis of the gallbladder cancer.

PMID- 10965314
TI  - Nitric oxide synthase inhibition negates bombesin-induced gastroprotection.
AB  - BACKGROUND: Bombesin prevents gastric injury primarily by the release of
      endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric
      oxide synthase inhibition, which implicates a role for nitric oxide as a
      protective mediator. Because both endothelial and inducible isoforms of this
      enzyme can play a role in mucosal defense, this study was done to examine the
      contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced
      gastroprotection. METHODS: Rats were given subcutaneous saline or bombesin (10
      100 microg/kg) 30 minutes before they received a 1-mL orogastric bolus of
      acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were
      killed 5 minutes later for assessment of macroscopic injury (mm(2)). Gastric
      mucosal blood flow was measured by laser Doppler. Endothelial, neural, and
      inducible nitric oxide synthase were assessed by using Western immunoblot.
      RESULTS: Bombesin decreased gastric mucosal damage, and dose-dependently
      increased blood flow when compared with saline-treated rats. Endothelial but not
      neural or inducible nitric oxide synthase immunoreactivity was increased by
      bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-l
      arginine methyl ester (l-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase
      inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the
      selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous
      (SC) l-arginine (300 mg/kg), but not d-arginine, abolished the effects of l-NAME.
      CONCLUSIONS: Taken together, these data suggest that nitric oxide produced by the
      endothelial isoform of nitric oxide synthase plays an important role in mediating
      the gastroprotective and hyperemic actions associated with bombesin.

PMID- 10965315
TI  - Functional importance of connective tissue repair during the development of
      experimental abdominal aortic aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) involve an unfavorable balance
      between the destruction and the repair of connective tissue proteins. The purpose
      of this study was to assess the functional importance of connective tissue repair
      during experimental aneurysmal degeneration. METHODS: Male Wistar rats (n = 70)
      underwent transient intraluminal perfusion of the abdominal aorta with porcine
      pancreatic elastase. In Study I, the aortic diameter was measured before elastase
      perfusion and at days 0, 2, 7, and 14 (n = 6 rats at each interval). Aortic wall
      concentrations of desmosine (Des) and hydroxyproline (OHP) were measured at each
      interval, and the expression of tropoelastin (TE), alpha1(I) procollagen (PC),
      and lysyl oxidase genes was evaluated by reverse transcription-polymerase chain
      reaction. In Study II, 22 rats were treated with beta-aminopropionitrile (BAPN)
      to block connective tissue repair. In Study III (n = 30), rats were treated with
      doxycycline, a matrix metalloproteinase inhibitor, beginning 7 days after
      elastase perfusion. RESULTS: AAAs consistently developed between 7 and 14 days
      after elastase perfusion. Aortic wall Des concentration decreased markedly during
      aneurysm development, reaching 3% of normal by day 14 (377 +/- 22 pmol of
      Des/sample on day 0 vs 9 +/- 1 pmol of Des/sample on day 14; P <.05). Aortic wall
      OHP decreased to only 68% of normal at the same interval (121 +/- 10 nmol of
      OHP/sample on day 0 vs 82 +/- 14 nmol of OHP/sample on day 14; P <.05). TE and PC
      expression was undetectable in healthy aorta, but they both increased by day 7 (P
      <.05); while TE expression decreased again by day 14, PC continued to rise. Lysyl
      oxidase expression progressively decreased at all intervals after elastase
      perfusion. Treatment with beta-aminoproprionitrile resulted in acute aortic
      dissection in 81% of the rats (50% mortality). These early deaths occurred
      between days 3 and 6, coinciding with aortic infiltration by proteinase-secreting
      inflammatory cells. Delayed treatment with doxycycline suppressed the progression
      of aneurysmal dilatation between days 7 and 21 (P <.05 vs untreated controls).
      CONCLUSIONS: The development of elastase-induced AAAs is accompanied by an active
      process of connective tissue repair. While this reparative process is necessary
      to stabilize the developing aneurysm wall, it is insufficient to prevent aneurysm
      progression. In contrast, reducing the proteolytic destruction of connective
      tissue proteins promotes stabilization of the aneurysmal aorta.

PMID- 10965316
TI  - Interstitial quinacrine for elimination of abnormal tissue; therapy of
      experimental glioma.
AB  - BACKGROUND: When quinacrine is injected interstitially, an intense migration of
      leukocytes and accumulation of various lymphokines is obtained locally, and the
      reaction is followed by cicatricial fibrosis. This property has been used in
      humans to induce tubal fibrosis in women and pleurodesis in patients with pleural
      effusion. METHODS: In a controlled study, a single dose of 150 mg of quinacrine
      was injected interstitially into a C6 glioma implanted in the subcutaneous tissue
      of Wistar rats. Changes in size, histologic variations, and microscopic
      characteristics of leukocyte subpopulations infiltrating the tumor were studied
      by immunohistochemistry. Tumor necrosis factor and interleukin-1 beta were
      measured at different times in tumor homogenates. RESULTS: The day after the
      injection of quinacrine, infiltration of leukocytes and macrophages was observed,
      accompanied by an accumulation of proinflammatory endogenous cytokines. Tumoral
      necrosis soon ensued; complete tumor disappearance was obtained in 72% of the
      animals. Cicatrization proceeded without injury of perilesional structures. In
      all controls injected with the vehicle, a large tumor developed (P <.0001).
      CONCLUSIONS: Quinacrine, when administered interstitially in a single dose,
      elicits an intense local recruitment and proliferation of activated immune cells
      that, at the dose used in this study, induces tissue necrosis within a radius of
      1 cm around the site of quinacrine injection, leaving the surrounding tissue
      unharmed.

PMID- 10965317
TI  - Development of an ex vivo model of pig kidney perfused with human lymphocytes.
      Analysis of xenogeneic cellular reactions.
AB  - BACKGROUND: Because of the explosive nature and the extremely rapid process of
      hyperacute rejection (HAR), significant infiltration of the xenograft by
      immunocompetent cells is not observed, and the role and the mechanism of action
      of cell-mediated rejection in discordant xenografts are therefore still under
      discussion. METHOD: We developed an experimental approach using pig kidneys
      perfused with human peripheral blood lymphocytes (PBL) in which the immunologic
      barrier of hyperacute rejection was excluded and which mimics the in vivo
      situation. RESULTS: PBL retention in the kidney was evaluated at 20-minute
      intervals for 3 hours. Retention increased from 30% to 80% with the time of
      perfusion and was specific because significantly fewer syngeneic lymphocytes were
      retained. Phenotype analysis of recovered PBL showed a significant decrease in
      natural killer (NK) cells. Immunohistochemical studies revealed the presence of
      NK cells and T lymphocytes in the glomerular and interstitial tubular structures
      of the kidney. Functional studies showed a progressive cessation of diuresis and
      augmentation of renal vascular resistance when the kidney was perfused with PBL.
      Electron microscopy examinations of kidney sections perfused with PBL showed
      swollen endothelial zones, suggesting alterations to and damage of the
      endothelium. CONCLUSIONS: This system provides a valuable model for the study of
      early discordant xenogeneic cellular rejection and demonstrates the predominance
      of xenograft infiltration by NK cells.

PMID- 10965318
TI  - Parathyroid-induced angiogenesis is VEGF-dependent.
AB  - BACKGROUND: Autotransplantation of parathyroid tissue after parathyroidectomy is
      successful at salvaging parathyroid function. The relatively high success of
      parathyroid transplantation is thought to be due, in part, to the ability of
      parathyroid tissue to induce angiogenesis and thus recruit a new vasculature.
      Vascular endothelial growth factor (VEGF) is a potent angiogenic factor produced
      by a number of tumors and hypoxic tissues. Using a 3-dimensional intact
      microvessel angiogenesis system, we evaluated the role of VEGF in the stimulation
      of angiogenesis by human parathyroid cells. METHODS: Freshly isolated rat
      microvessels embedded in a 3-dimensional collagen I matrix were treated with
      healthy 1-mm(3) fragments of human parathyroid tissue or isolated parathyroid
      cells. Other gels were supplemented with VEGF(165) or FLT-1 soluble receptor
      fusion protein to bind VEGF. After 11 days in culture, the gels were stained with
      Gs-1 lectin, a marker for rat endothelium, and linear growth of the microvessels
      was determined by using image analysis. Parathyroid production of VEGF was
      determined with reverse transcriptase-polymerase chain reaction. RESULTS: A
      significant increase in microvessel growth was seen in parathyroid coculture (8.4
      +/- 1.0 mm) versus VEGF(165) supplemented gels (6.2 +/- 0.3 mm, P <.01).
      VEGF(165) significantly augmented parathyroid-stimulated angiogenesis (13.7 +/-
      2.4 mm, P <.05 vs parathyroid alone). Using quantitative reverse transcriptase
      polymerase chain reaction, we identified VEGF messenger RNA (mRNA) induction
      within 1 hour of parathyroid explant, with a 12-fold increase by 24 hours.
      Treatment of parathyroid cocultures with 0.2 microg/mL FLT-1 soluble receptor
      protein completely eliminated the parathyroid induction of angiogenesis.
      CONCLUSIONS: Parathyroid tissue expresses low levels of VEGF mRNA, which is
      significantly upregulated on explantation. Furthermore, the increased VEGF
      expression is essential to drive parathyroid-induced angiogenesis in our model.
      However, our data suggests that other parathyroid-produced factors are involved
      in mediating parathyroid-induced angiogenesis.

PMID- 10965319
TI  - Effect of resident call status on ABSITE performance. American Board of Surgery
      In-Training Examination.
AB  - BACKGROUND: Long work hours that result in fatigue may adversely affect cognitive
      function. Chronically sleep-deprived surgical residents fear that being on call
      the night before sitting for a standardized test puts them at a potential
      disadvantage. We examined American Board of Surgery In-Training Examination
      (ABSITE) scores to assess the effect of call status on exam performance. METHODS:
      Results of the 1994 ABSITE for 424 residents in 15 New England general surgery
      programs were collected. We compared standard scores of residents for the total
      test, clinical management, and basic science components with resident call status
      (on/off) for the night before the exam. RESULTS: Differences were apparent in
      total test scores (mean: off, 496.1; on, 466.0; P <.03) and clinical management
      scores (mean: off, 504.3; on, 470.6; P <.02) (t test, Mann-Whitney U test).
      Multivariate analyses revealed that differences in postgraduate year level and
      training track were significant contributors to differences in scores in all test
      components (analysis of covariance). Call status was not a significant factor in
      score variation after adjusting for these 2 factors. CONCLUSIONS: Differences in
      ABSITE scores of residents were related to postgraduate year level and training
      track. Call status had no significant effect on ABSITE performance.

PMID- 10965320
TI  - Is lower extremity revascularization worthwhile in patients with end-stage renal
      disease?
AB  - BACKGROUND: The purpose of this study was to review the results of lower
      extremity revascularization in patients with end-stage renal disease and to
      determine in these patients the functional benefit and cost of an aggressive
      approach to limb preservation. METHODS: During a 5-year period at our
      institution, 33 bypass operations were performed on 31 limbs of 23 dialysis
      dependent patients. Indications for revascularization were limited (18) or
      extensive (12) tissue loss or ischemia without tissue loss (3). Procedures
      included aortobifemoral bypass (1), femoropopliteal bypass (10), and
      femorotibial/pedal bypass (22). A digital or transmetatarsal amputation was
      performed in 57% of limbs. RESULTS: The 30-day primary patency was 100%.
      Cumulative primary and secondary patency rates at 2 years were 65% and 79%,
      respectively. Limb salvage was 67% and 59% at 1 and 2 years, respectively.
      Patient survival was poor (47% at 2 years). Peritoneal dialysis was predictive of
      poor survival (P <.001). Four of 5 patients on peritoneal dialysis died within 3
      months of intervention. Extensive tissue loss was predictive of a diminished rate
      of limb salvage (P =.027). Only 39% of limbs with extensive tissue loss were
      salvaged at 1 year compared with 78% and 100% of limbs with limited and no tissue
      loss, respectively. The average hospital cost was $44,308 per year of limb
      salvage. CONCLUSIONS: Although revascularization of ischemic limbs in dialysis
      patients can be achieved with an excellent initial graft patency and reasonable
      limb salvage, patient survival is poor and costs are high. A selective approach
      to revascularization in these complicated patients may be indicated. For patients
      treated with peritoneal dialysis and for those with extensive tissue loss,
      primary amputation may be the preferred approach.

PMID- 10965321
TI  - Gastric outlet obstruction secondary to wandering spleen.

PMID- 10965323
TI  - The power behind the chair

PMID- 10965322
TI  - Pheochromocytoma presenting as a giant cystic tumor of the liver.

PMID- 10965324
TI  - Partial abdominal exenteration, ex vivo resection of a large mesenteric fibroma,
      and successful orthotopic intestinal autotransplantation.

PMID- 10965325
TI  - Distal pancreatectomy using the harmonic scalpel.

PMID- 10965326
TI  - Bile duct carcinogenesis after excision of extrahepatic bile ducts in
      pancreaticobiliary maljunction.

PMID- 10965327
TI  - Mesenteric arterial thrombosis due to activated protein C resistance (factor V
      Leiden)

PMID- 10965328
TI  - Laparoscopic intracavitary debridement of peripancreatic necrosis.

PMID- 10965329
TI  - Reply

PMID- 10965330
TI  - Pediatric oncology in Amsterdam.

PMID- 10965331
TI  - SIOP abstract contents

PMID- 10965333
TI  - SIOP abstracts (O-58 to O-117)

PMID- 10965332
TI  - SIOP abstracts (O-1 to O-57)

PMID- 10965334
TI  - SIOP abstracts (O-118 to O-151)

PMID- 10965335
TI  - SIOP abstracts (GL-2 to GL-13)

PMID- 10965336
TI  - SIOP abstracts (SL-1 to SL-34)

PMID- 10965337
TI  - SIOP abstracts (IL-2 to IL-26)

PMID- 10965338
TI  - SIOP abstracts (TL-4)

PMID- 10965339
TI  - SIOP abstracts (P-1 to P-61)

PMID- 10965340
TI  - SIOP abstracts (P-62 to P-121)

PMID- 10965341
TI  - SIOP abstracts (P-122 to P-181)

PMID- 10965342
TI  - SIOP abstracts (P-182 to P-242)

PMID- 10965343
TI  - SIOP abstracts (P-243 to P-303)

PMID- 10965344
TI  - SIOP abstracts (P-304 to P-365)

PMID- 10965346
TI  - SIOP abstracts (U-1 to U-60)

PMID- 10965345
TI  - SIOP abstracts (P-366 to P-423)

PMID- 10965347
TI  - SIOP abstracts (U-61 to U-83)

PMID- 10965349
TI  - IPSO meeting program

PMID- 10965350
TI  - IPSO abstracts

PMID- 10965352
TI  - Effects of the dimethyl ester on succinic acid on the hormonal and metabolic
      response to exercise in hereditarily diabetic starved rats.
AB  - This study was designed to assess the effect of the dimethyl ester of succinic
      acid (SAD) upon the hormonal and metabolic response to a 60-min exercise in
      overnight-starved Goto-Kakizaki rats. Twenty Goto-Kakizaki rats were starved
      overnight and then either maintained at rest or obliged to swim for 60 min. Half
      of the rats were injected intraperitoneally with the dimethyl ester of succinic
      acid (SAD, 5.0 micromol g(-1) body wt) immediately before exercise (or 60 min of
      rest). In the hereditarily diabetic rats, overnight starvation lowered the plasma
      D- glucose, insulin and lactate concentrations, while increasing that of free
      fatty acids and beta-hydroxybutyrate. In resting rats, the injection of SAD
      increased the glycogen content of liver, heart and muscle and the plasma
      concentration of D-glucose, insulin, glycerol and free fatty acids. In control
      animals, not injected with SAD, exercise increased the plasma concentration of D-
      glucose, lactate and glycerol, whilst lowering both that of insulin and the
      glycogen content of liver, heart and muscle. The injection of SAD before exercise
      failed to prevent and, on occasion, even accentuated the changes in both the
      glycogen content of liver, heart and muscle and the plasma concentration of D
      glucose, insulin, glycerol and free fatty acids, whilst minimizing the increase
      in lactate concentration otherwise caused by exercise. Nevertheless, the
      comparison between resting and exercising rats, both injected with SAD, suggested
      that the ester abolished the exercise-induced rise in D-glucose, glycerol and
      fatty acid concentrations. By comparison with comparable experiments conducted in
      overnight-starved normal rats, these findings emphasize both the difference
      between normal and diabetic rats in their metabolic response to exercise,
      especially in terms of changes in glycemia, and the usefulness of SAD to
      compensate for the increased consumption of endogenous nutrients during exercise.

PMID- 10965353
TI  - Insulin uptake, localization and production in previously insulin treated and
      untreated Tetrahymena. Data on the mechanism of hormonal imprinting.
AB  - Confocal microscopic experiments demonstrate the presence of insulin in
      Tetrahymena, observed also in earlier experiments. However, there is a broad
      spectrum of insulin-containing cells from the immunocytochemically insulin-free,
      to the strongly antibody-reactive ones. During 1 h of insulin treatment
      (imprinting) the cells gradually bind and take up insulin, and the process is
      slow. One minute after the start of treatment there is not difference in the
      number of insulin antibody-reactive cells and amount of insulin. After 5 or 10
      min the cells bind and contain more insulin and after 1 h most of the cells are
      densely packed with the insulin antibody-reactive material. Insulin imprinting
      accelerates binding and uptake alike: 48 h after imprinting and 1 min after the
      start of the second treatment, more insulin is present on the surface and inside
      the cells, than after 10 min in the first-time treated cells. Theoretically, this
      effect of hormonal imprinting helps to maintain the species by facilitating
      molecular recognition and binding as well as uptake of useful molecules. The
      experiments also support previous observations on the parallel receptor-evoking
      (strengthening) and hormone-producing effect of hormonal imprinting.

PMID- 10965354
TI  - Antioxidants and lipid peroxidation status in the blood of patients with
      alopecia.
AB  - The aim of this research was to determine levels in blood of vitamin E, beta
      carotene, lipid peroxidation as thiobarbituric-acid reactive substances (TBARS)
      and reduced glutathione (GSH) and activity of glutathione peroxidase (GSH-Px) in
      patients with alopecia. Studies were carried out on 37 patients with alopecia and
      34 healthy age-matched controls. Red blood cell (RBC) and plasma samples from
      healthy and patient subjects were taken. Beta-cartotene levels (P<0. 001) in
      plasma and levels of GSH (P>0.05) and the activity of GSH-Px (P<0.05, P<0.01) in
      both plasma and RBC samples were significantly lower in patients with alopecia
      than in controls, whereas TBARS levels in plasma (P<0.05) and RBC (P<0.001)
      samples were significantly higher in patients with alopecia than in controls.
      However, vitamin E levels in plasma did not differ statistically. Although being
      far from conclusive, these results provide some evidence for a potential role of
      increased lipid peroxidation and decreased antioxidants in alopecia.

PMID- 10965355
TI  - Hepatic changes in the freeze-tolerant turtle Chrysemys picta marginata in
      response to freezing and thawing.
AB  - Select hepatic changes in the freeze-tolerant hatchling turtle, Chrysemys picta
      marginata, were studied in response to freezing at -2.5 degrees C and thawing.
      Upon freezing, a small, selective increase in the liver weight with no increase
      in body weight was seen suggestive of an hepatic capacitance response. In all
      turtles studies, lobular differences in the hepatic content of glycogen were
      evident: the smaller lobe contained twice as much glycogen as the larger lobe.
      The response to freezing and thawing was comparable. Total hepatic glycogen
      levels of turtles were reduced approximately 60 per cent from control levels in
      the frozen state and recovered to >80 per cent of control levels in the thawed
      state. Compared to the control state, turtle blood glucose levels were: unchanged
      after 12 h in the cool state; reduced 28 per cent after 24 h and increased two
      fold after 48 h in the frozen state; and increased 4.5-fold in the thawed state.
      Thus, changes in hepatic glycogen metabolism occur without large changes in blood
      glucose levels. In turtle liver plasma membranes, the hepatic alpha(1)-adrenergic
      receptor was barely detectable and did not change. The beta(2)-adrenergic
      receptor was expressed at high levels and, compared to control levels, was:
      unchanged after 12 h in the cool state; reduced 20 per cent after 24 h and 40 per
      cent after 48 h in the frozen state. On thawing, this receptor was 50 per cent of
      control levels. While catecholamines working through the beta(2)-adrenergic
      receptor may effect early hepatic glycogen breakdown in response to freezing,
      other factors must be involved to complete the process. The plasma membrane-bound
      enzyme gamma-glutamyltranspeptidase displayed a different pattern of changes
      indicative of selective modulation: it was increased 2.7-fold over control levels
      in the cool state; unchanged in the frozen state; and increased 1.8-fold in the
      thawed state. The activity of the kidney enzyme was decreased in the cool state
      and slightly increased in the frozen and thawed states emphasizing the tissue
      specific nature of the changes in the activity of gamma-glutamyltranspeptidase in
      response to freezing and thawing. The similarities and differences of the hepatic
      changes in response to freezing and thawing in the freeze-tolerant hatchling
      turtle to those we have previously reported for the freeze-tolerant frog are
      discussed.

PMID- 10965356
TI  - Metabolic effects induced by epinephrine in Rana balcanica erythrocytes under
      normoxic and hypoxic conditions.
AB  - The metabolic effects of epinephrine on Rana balacanica erythrocyte suspension
      were studied under normoxia and hypoxia. After epinephrine treatment, a 1.2-fold
      increase of lactate formation and a 20 per cent decrease of ATP concentration was
      found under normoxic conditions. These effects were rapid and specific to beta,
      alpha(1) and alpha(2) antagonists. Glycolysis was stimulated to almost the same
      extent by both epinephrine and forskolin as normoxic conditions. The stimulation
      of glycolysis was probably due to stimulation of phosphofructokinase (PFK) as
      well as to activation of Na(+), K(+)-ATPase. The decrease of ATP was a
      contributing factor to PFK activation. Despite the high levels of c-AMP at
      hypoxia, glycolysis was not further induced by epinephrine.

PMID- 10965357
TI  - N-acetylcysteine increases apoptosis induced by H(2)O(2) and mo-antiFas
      triggering in a 3DO hybridoma cell line.
AB  - N-Acetylcysteine (NAC) has been used as an antioxidant to prevent apoptosis
      triggered by different stimuli in different cell types. It is common opinion that
      cellular redox, which is largely determined by the ratio of oxidized and reduced
      glutathione (GSH), plays a significant role in the propensity of cells to undergo
      apoptosis. However, there are also contrasting opinions stating that
      intracellular GSH depletion or supplemented GSH alone are not sufficient to lead
      cells to apoptosis or conversely protect them. Unexpectedly, this study shows
      that NAC, even if it maintains the peculiar characteristics of an agent capable
      of reducing cell proliferation and increasing intracellular GSH content,
      increases apoptosis induced by H(2)O(2) treatment and mo-antiFas triggering in a
      3DO cell line. We found that 24 h of NAC pre-treatment can shift cellular death
      from necrotic to apoptotic and determine an early expression of FasL in a 3DO
      cell line treated with H(2)O(2).

PMID- 10965358
TI  - Action of 2-nonenal and 4-hydroxynonenal on phosphoinositide-specific
      phosopholipase C in undifferentiated and DMSO-differentiated HL-60 cells.
AB  - The promyelocytic cell line HL-60 has been used as an in vitro model to study the
      mechanism of action of two chemotactic aldehydes, 2-nonenal and 4-hydroxynonenal.
      Increasing aldehyde concentrations have been added to undifferentiated and DMSO
      differentiated cells incubated at 37 degrees C and their effect on
      phosphoinositide-specific phospholipase C has been analysed by using a specific
      inositol-1,4,5-tris-phosphate assay system. Concentrations of 2-nonenal between
      10(-9) and 10(-7) M significantly increased the enzymatic-activity in DMSO
      differentiated HL-60 cells, while 10(-9) and 10(-8) M concentrations were active
      in the undifferentiated cells. 4-Hydroxynonenal was able to activate
      phospholipase C both in undifferentiated and DMSO-differentiated cells at
      concentrations ranging from 10(-8) to 10(-6) M. The concentrations of both
      compounds active on phospholipase C displayed a good correspondence with those
      which had been reported to be chemotactic towards rat neutrophils. In the case of
      4-hydroxynonenal, the present results confirm its ability to activate
      phospholipase C, which we had previously shown in isolated neutrophil plasma
      membranes. The comparison of the effects of 2-nonenal and 4-hydroxynonenal on
      chemotaxis and phospholipase C activation suggests a common mechanism of action
      for both aldehydes, for which the presence of the double bond seems to be
      required.

PMID- 10965359
TI  - EGF enhances Ca(2+) mobilization and capacitative Ca(2+) entry in mouse mammary
      epithelial cells.
AB  - Effects of epidermal growth factor (EGF) on the intracellular Ca(2+)
      ([Ca(2+)](i)) responses to nucleotides, Ca(2+) release from thapsigargin
      sensitive stores and capacitative Ca(2+) entry were investigated in cultured
      mouse mammary epithelial cells. EGF treatment induced proliferation of mammary
      epithelial cells. We checked for mitotic activity by immunocytochemistry with an
      anti-PCNA (proliferating cell nuclear antigen) antibody, which stains nuclei of
      the cells in S-phase of cell cycle. EGF treatment apparently increased the number
      of PCNA-stained cells compared to those treated with differentiating hormones
      (insulin, prolactin and cortisol) or without any hormone. Application of EGF did
      not induce any acute [Ca(2+)](i) response. EGF treatment for 1-2 days in culture,
      however, enhanced [Ca(2+)](i) responses including [Ca(2+)](i) increase by ATP,
      UTP and other nucelotides, Ca(2+) release from thapsigargin-sensitive stores, as
      well as capacitative Ca(2+) entry. Genistein, a tyrosine kinase inhibitor,
      prevented EGF-induced cell proliferation and the [Ca(2+) ](i) responses in a dose
      dependent manner. These results indicate that EGF treatment enhances Ca(2+)
      mobilization and capacitative Ca(2+) entry, well correlated with cellular
      proliferation in mammary epithelial cells.

PMID- 10965360
TI  - Dental histology: study of aging processes in root dentine.
AB  - The amount of sclerotic root dentine increases with age, proceeding from the apex
      towards the crown. There are obvious optical changes in the tissue, which becomes
      translucent (dentine is normally opaque). Therefore, the sclerosis of root
      dentine could be a reliable indicator of age in anthropological studies of human
      remains. We studied the histological aspects of sclerotic dentine in longitudinal
      thin sections (70-140 microns) of undecalcified premolars, cut in the bucco
      lingual plane. To quantify the sclerosis and to construct a reference standard,
      we sectioned 85 premolars from subjects of known age (70 from odontological
      extractions and 15 from a university collection). Another 10 teeth from medieval
      subjects were studied to assess the applicability of the method to ancient
      skeletal collections. The technique consists of embedding the tooth in a
      polyester resin (cold method), sectioning it with a diamond blade microtome.
      Qualitative analysis was performed with polarized light microscopy and
      measurements were made with a quote 2D x,y viewer and on digital images. The
      sclerotic root dentine was quantified with both linear and surface area
      parameters in order to assess the correlation with age. The quality of the
      sections was sufficient for the clear discernment and quantification of the
      sclerotic dentine. Indeed, the technique allowed us to obtain good results with a
      considerable saving of time and money compared with other dental histological
      techniques. The best correlation with age was obtained from the surface area
      parameter, particularly after exclusion of the cementum and pulp chamber. To
      produce comparable data from similar studies, we advise the use of cold resins,
      as used here, and digital computerized analyzers because of their accuracy,
      precision and quickness. The qualitative analysis of the ancient teeth
      indications that this dental aging techniques can be applied to both recent and
      ancient dental tissues.

PMID- 10965361
TI  - Poly(ADP-ribose) polymerase activity in regenerating liver of hypothyroid rats.
AB  - The role of PARP, a nuclear enzyme involved in DNA synthesis, repair and cell
      transformation, was studies during liver regeneration in hypothyroid animals.
      Hypothyroidism was induced by in vivo administration of propylthiouracil. In
      regenerating euthyroid animals PARP activity is stimulated showing an early and
      significant increase at 1.5 h with a maximum at 6 h after partial hepatectomy.
      Such an increase returns to control values within 18 h preceding the onset of DNA
      synthesis. A markedly different behavior, with respect to euthyroids, has been
      evidenced in hypothyroid rats. At first, liver PARP level was about 2-fold higher
      in non regenerating hypothyroid rats with respect to control euthyroids. During
      regeneration, PTU-treated animals show a net decrease in PARP activity, with a
      minimum at 6-9 h after partial hepatectomy. The activity returns to control
      levels within 24 days. The minimum in PARP activity anticipates, also in this
      case, the onset of DNA synthesis, which exhibits a maximum at 15-18 h. During
      liver regeneration PARP activity shows modifications related to the beginning of
      de novo DNA synthesis. Furthermore, these variations in turn undergo the effects
      of hypothyroidism.

PMID- 10965362
TI  - Reduction of cutaneous blood flow in cold fingers.
AB  - Blood flow to fingers is reduced during cold exposure. This is generally
      attributed to vasoconstriction. We tested the hypothesis that increased blood
      viscosity, not vasoconstriction, accounts for reductions of cutaneous flow after
      fingers cool. Blood viscosity was higher at 10 degree C than at 27 degree C and
      independent of hematocrit at low shear rates. The increase of finger vascular
      resistance may be due to increased vascular hindrance early in cold exposure (<
      15 min) and is more likely due to increased viscosity after 20-30 min, a factor
      that may dominate the peripheral microcirculaton during prolonged cold exposure.

PMID- 10965363
TI  - [Acute encephalopathy in children: a serious illness after an inauspicious
      beginning].
AB  - Three young children, 2 girls of 6 and 3.5 years and 1 boy aged 3.5 years, had
      complaints like vomiting and fever of what initially was thought to be a minor
      infection. However, their condition deteriorated within two days to such an
      extent that they died while being treated on the intensive care department. The
      rapid drop in consciousness, sometimes accompanied by convulsions, is an
      expression of increased intracranial pressure resulting from diffuse brain
      oedema, which itself is probably caused by circulating toxins. The treatment of
      acute toxic encephalopathy is purely symptomatic.

PMID- 10965364
TI  - [Impact of the new guidelines for adjuvant systemic treatment of breast cancer at
      hospital level].
AB  - Recently, the Dutch Society for Medical Oncology published new consensus
      guidelines for the use of adjuvant systemic treatment in patients with operable
      breast cancer. We used data of the cancer registry of the Comprehensive Cancer
      Centre South to predict the change in the number of patients who will be
      candidates for systemic treatment according to these new guidelines. It was
      estimated that of all patients with operable breast cancer, 15% should receive
      chemotherapy, 27% hormonal therapy and 17% a combination of both modalities. Of
      the patients with negative axillary lymph nodes, one-third will receive adjuvant
      systemic treatment. Compared with the previous guidelines, the introduction of
      the new guidelines will cause a 50% increase in the number of patients receiving
      adjuvant systemic treatment in Dutch hospitals.

PMID- 10965365
TI  - [New insights in frontotemporal dementia].
AB  - Frontotemporal dementia (FTD) is a neurodegenerative disorder characterised by
      progressive behavioural disturbance, aphasia and a decline in frontal cognitive
      functions. Frontotemporal atrophy on CT and MRI, and hypoperfusion of the frontal
      brain regions on single-photon emission computed tomography (SPECT), are
      characteristic findings. Neuropathological examination reveals deposition of
      abnormally phosphorylated tau protein in neurons and glial cells in a number of
      the sporadic and familial cases, while aspecific changes with neuronal loss,
      spongiosis and gliosis are found in the remaining cases. A familial form with an
      autosomal dominant pattern of inheritance is seen in 20% of FTD patients.
      Mutations in the tau gene have been identified in a number of families with
      deposition of abnormal tau protein in affected brain regions. Presymptomatic DNA
      testing is now available for relatives of patients with tau mutations, but must
      only be considered after extensive genetic counselling in a centre with
      neurogenetic expertise.

PMID- 10965366
TI  - [Roaming through methodology. XXI. How to arrive at a weighed total score of
      separate items of a questionnaire].
AB  - In medical research the responses of patients to a number of items are often
      combined into a summary measure or total score for a more general patient
      characteristic, such as mobility. Clinical and statistical criteria exist for
      determining the weight of each question in the total score. The choice of weights
      may affect the differences between patients. The total score is often analysed
      statistically as if it had interval level of measurement, thereby allowing
      conclusions about the size of differences between patients, but it has merely an
      ordinal level. The incorrectness of the interval assumption may also affect
      differences between patients or patient groups. Finally, differences between
      patients are less dependent on the weighting of the items and on the assumption
      of an interval scale as the total score is based on more homogeneous items.
      Standard statistical software contains statistical methods for determining the
      homogeneity as well as the weights.

PMID- 10965367
TI  - [Absence of epiphora in patients with a monocanalicular injury without surgical
      reconstruction].
AB  - OBJECTIVE: To determine the long-term outcome in patients with a lesion of a
      single lacrimal canaliculus without surgical correction. DESIGN: Prospective.
      METHOD: In the period August 1995-August 1999 16 patients were seen with a
      monocanalicular trauma. No attempt was made to reconstruct the canaliculus; only
      the superficial layers were closed (skin and M. orbicularis oculi). At follow-up
      the patients were asked about epiphora (score of Munk) and the test of Anel and
      the fluorescein dye disappearance test were carried out. RESULTS: At follow-up a
      mean of 13.7 months (range: 3-33) after the trauma the injured canaliculus was
      totally blocked in all patients. In spite of this, none of the patients
      experienced epiphora either indoors or outdoors. Tear drainage of the ipsilateral
      unharmed canaliculus was functioning normally in such a way that epiphora was
      prevented. CONCLUSION: In patients with a monocanalicular lesion repair of only
      the superficial layers of the eyelid without reanastomosis of the torn ends of
      the canaliculus is sufficient to maintain normal tear drainage. This procedure is
      safe and simple.

PMID- 10965368
TI  - [Immunology in the medical practice.XXXII. Transplantation of autologous
      hematopoietic stem cells for treatment of refractory auto-immune diseases;
      preliminary favorable results with 35 patients].
AB  - The objective of this study was to document the experiences in the first Dutch
      pilot studies of the effect of transplantation of autologous haematopoietic stem
      cells in patients with therapy-resistant autoimmune disease. The first results in
      21 adults and 14 children are promising: remission of the disease was achieved in
      13 patients, while in the others a significant reduction of disease activity was
      seen with a corresponding improvement of the quality of life. Infectious
      complications were frequently observed. Two children with systemic juvenile
      idiopathic arthritis developed a fatal infection-associated macrophage activation
      syndrome. Multicentre randomised studies are necessary to study the effects of
      autologous stem cell transplantation and modifications such as T-cell depletion.

PMID- 10965369
TI  - [Congenital amegakaryocytic thrombocytopenia: indication for allogeneic stem cell
      transplantation].
AB  - In two neonates, girls, persistent thrombocytopenia was found, which afterwards
      proved to be caused by a megakaryocytosis. Congenital amegakaryocytic
      thrombocytopenia is a rare bone marrow failure in young children that is defined
      as thrombocytopenia with absent or markedly decreased megakaryocytes in the bone
      marrow. Untreated, amegakaryocytic thrombocytopenia progresses to marrow failure
      with pancytopenia. Allogeneic stem cell transplantation offers the only
      possibility for cure, and is successful in approximately half of the patients.
      Both patients were treated by stem cell transplantation, the one with a matched
      unrelated donor, the second with stem cells from her HLA-identical sister. The
      first patient died, the second recovered with a normal number of circulating
      thrombocytes of donor origin.

PMID- 10965370
TI  - [Evaluation of added value of diagnostic tests].

PMID- 10965371
TI  - [Evaluation of added value of diagnostic tests].

PMID- 10965372
TI  - [Mechanical ventilation in neuromuscular diseases: do not start too early, but
      certainly not too late].

PMID- 10965373
TI  - [Fecal incontinence: prevalence and role of anal sphincter rupture during labor;
      review of literature].

PMID- 10965374
TI  - Biological variability of myoglobin in healthy elderly and younger subjects.
AB  - To study the effect of age on serum myoglobin more clearly, the analytical, intra
      individual and inter-individual components of variation were estimated from
      duplicate analyses of specimens collected from 18 healthy elderly subjects [ages
      74-97 years; 9 men (EM)], and 14 healthy younger subjects [ages 25-31 years; 7
      men (YM)] over a period of 6 weeks. The mean values (microgram/L) were EM: 53.7;
      EW: 44.9; YM: 34.2; YW:24.8. Estimated analytical (CVA), intra- (CVI) and inter
      individual (CVG) variations as CV% were: CVA: 2.2. CVI: EM: 13; EW: 9.9; YM:
      12.4; YW: 9.6. CVG: EM: 37.6; EW: 28; YM: 18.5; YW: 13.4. The data obtained were
      used to derive the desirable analytical goal for imprecision (i.e., < or = 6.5%
      in EM; < or = 4.9% in EW and < or = 6.2% in YM; < or = 4.8% in YW); inaccuracy
      (i.e., < or = 9.9% in EM; < or = 7.7 in EW and < or = 5.5% in YM; < or = 4.12% in
      YW); the change required for serial results to be significantly different (i.e.,
      36% in EM; 28% in EW and 34% in YM; 27.2% in YW), the numbers of specimen
      collections required to produce a more precise estimate of the homeostatic set
      point of an individual within 5% (i.e., 26 in EM; 16 in EW and 24 in YM; 15 in
      YW), and the index of individuality (i.e., 0.34 in EM; 0.35 in EW and 0.67 in YM;
      0.71 in YW). This study shows that intra-individual biological variation of
      myoglobin in healthy elderly subjects is not different from that in young
      subjects. Inter-individual variation, instead, is greatly influenced by
      differences in age and sex.

PMID- 10965375
TI  - Nutrition and quality of life in the aged: the Jerusalem 70-year olds
      longitudinal study.
AB  - Inadequate nutrition is a major problem of elderly people today. Yet, despite the
      prevalence and significance of the problem, there is little information on the
      nutritional status of elderly persons in the community, and its impact on their
      quality of life. During 1990-1991, as part of a first cross-section in a
      longitudinal medical and social study of 70-year olds in Jerusalem, we surveyed
      the nutritional status of this population. During the first phase, 605 people
      were examined in their homes; data were collected regarding socioeconomic status,
      education, self-perceived health state, use of medications and health services,
      and ADL. During the second stage, a sub-group of 463 people was examined in a
      geriatric outpatient clinic; all subjects underwent medical history, physical
      examination, cognitive assessment, psychiatric questionnaire, blood and urine
      tests, electrocardiogram, and pulmonary function tests. In addition, general
      hospital admissions and morbidity and mortality in the two years following the
      study were studied. The nutritional status of the participants was determined
      according to nutritional assessment (NA) scale, based on the Mini Nutritional
      Assessment (MNA). The majority of the study population lived at home, was without
      cognitive disturbance (86%), and was independent in ADL (83%). Based on NA > 24,
      91% of the study population were in good nutritional state, 8.3% were at risk of
      undernutrition, and 0.7% were malnourished. There was a significant positive
      relationship between NA score and ADL as well as cognitive state. In addition, a
      strong negative relation was found between NA score and visits to the family
      physician in the previous fortnight, visits to the emergency room in the previous
      year, and hospital admissions in the following two years. An inverse relation,
      although not significant, was found between NA score and two-year post-study
      mortality. These results suggest that the nutritional status of the studied
      population is inadequate, and that the nutritional state is one of the major
      determinants of the quality of life in the elderly and therefore, should be part
      of any geriatric assessment. Elder population surveys are needed to identify and
      treat at risk elders.

PMID- 10965376
TI  - Maximal oxygen uptake, muscle strength and walking speed in 85-year-old women:
      effects of increased physical activity.
AB  - This study explores the effect of regular training on blood pressure, maximal
      oxygen uptake, maximal isometric muscle strength, and walking speed in the very
      old. A total of 55 community-dwelling women, 85-year-old, were enrolled in a
      training group (N = 22) or a control group (N = 33). These groups were reduced to
      19 and 26 subjects, respectively, after the training period. Training was
      performed once a week over eight months, and consisted of various exercises with
      particular attention to movements important for everyday activities. Training
      reduced diastolic blood pressure (p < 0.05), and showed a similar trend for
      systolic blood pressure. Measurements of maximal oxygen uptake before the start
      of the training (15 mL min-1 kg-1) revealed a level close to the presumed limit
      for independent living (13 mL min-1 kg-1). Training improved VO2 max by 18% (p <
      0.05), whereas the control group experienced a trend towards a reduction. Maximal
      isometric muscle strength of both the right and left leg showed a tendency to
      increase with training, but no significant changes were evident in the trunk
      flexor and extensor muscles. The training group showed a significant increase of
      17% in maximal walking speed after the training period. However, one year later,
      without training, this improvement was reduced to 8% (p < 0.05). No major changes
      were observed in the control group for any of these parameters. This study
      demonstrates a maximal oxygen capacity in very old community-dwelling women close
      to a threshold level indicating dependency. Furthermore, 8 months of regular
      training appears to lower blood pressure, and to increase maximal oxygen uptake
      and maximal walking speed. This suggests that physical reactivation of the very
      old may reduce the risk for acquiring age-related diseases associated with an
      elevated blood pressure, and may improve parameters crucial for independence.

PMID- 10965377
TI  - Mobility limitations in the Swedish population from 1968 to 1992: age, gender and
      social class differences.
AB  - Mobility limitations are closely related to disability in old age. The study of
      mobility limitations in the population may improve the understanding of the
      development of disability, as well as gender and class patterns in disability in
      old age. Representative samples of the Swedish population between the ages of 18
      and 75 years were interviewed in 1968, 1974, 1981, and 1991. A further sample of
      people aged 76+ years was interviewed in 1992. The questionnaire included the
      ability to walk 100 meters, to walk up and down stairs, and to run 100 meters.
      Mobility limitations begin to appear around age 40 years, and increase with age.
      In 1992 nearly none in the oldest age group (85+) could run 100 meters, and less
      than half could walk 100 meters, or go up and down stairs without difficulty.
      Between 1968 and 1991, the proportion of people with mobility limitations was
      reduced by one third, with the most prominent reduction among the oldest age
      groups. Women were more likely to report mobility limitations compared to men at
      all waves; however, the gender difference decreased between 1968 and 1991. Blue
      collar workers had more mobility limitations than white-collar workers, and this
      discrepancy did not decrease over time. Mobility limitations often begin early in
      life, and differences between cohorts, men and women, and social classes can be
      seen well before the age of 50. The results suggest that gender differences in
      functional limitations among elderly people may decrease in the future, while
      social class inequalities are likely to persist.

PMID- 10965378
TI  - Treatment of cobalamin deficiency in dementia, evaluated clinically and with
      cerebral blood flow measurements.
AB  - We investigated the relation between cobalamin deficiency, clinical changes and
      brain function in dementia patients. On admittance to the clinic, 24 patients had
      cobalamin deficiency, and dementia with additional symptoms of delirium. During
      cobalamin supplementation, the patients underwent repeated regional cerebral
      blood flow (rCBF) studies, psychiatric evaluations, and in some cases assessment
      with MMSE and the Organic Brain Syndrome scale. Fifteen patients who showed mild
      to moderate dementia improved clinically, and also showed a concomitant increase
      in their general CBF after treatment. In contrast, 9 patients who were severely
      demented showed no obvious clinical improvement, and no general blood flow
      change, although some regional flow increases were seen in sensory motor areas.
      We conclude that symptoms which probably indicated superimposed delirium such as
      clouding of consciousness, disorientation and clinical fluctuation, responded to
      the vitamin B12 supplementation, while the underlying dementia condition remained
      basically unchanged. The clinical improvement was also mirrored in general and
      focal rCBF changes.

PMID- 10965379
TI  - Modeling impairment: using the disablement process as a framework to evaluate
      determinants of hip and knee flexion.
AB  - Elders often present to health care providers with multiple inter-related
      conditions that determine an individual's ability to function. The disablement
      process provides a generalized sociomedical framework for investigating the
      complex pathways from chronic disease to disability. At each stage of the main
      pathway, associations may exist among primary physical factors and modifying
      variables that ultimately have downstream effects on the progression toward
      disability. The purpose of the present analysis is to examine the inter
      relationships between a cohesive set of variables primarily at the level of
      impairment that may affect hip and knee flexion range of motion (ROM). The San
      Antonio Longitudinal Study of Aging enrolled 833 community dwelling Mexican (MA)
      and European American (EA) elders aged 64-78 years between 1992 and 1996. Of
      these, 647 had complete data from both a home-based and performance-based battery
      of assessments for these analyses. Concerning impairments, hip ROM was measured
      using an inclinometer, and knee ROM using a goniometer. Pain location and
      intensity were assessed using the McGill Pain Questionnaire. Peripheral vascular
      disease was assessed using doppler brachial and ankle systolic blood pressures.
      Ankle and knee reflexes, and vibratory sensation were assessed by a standardized
      neurological examination. As to diseases, diabetes was assessed using a
      combination of blood glucose levels and self-report, and arthritis by self
      report. Concerning modifying variables, height and weight were directly measured
      and used to calculate BMI. Activity level was assessed with the Minnesota Leisure
      Time Questionnaire. Analgesic use was assessed by direct observation of
      medications taken within the past two weeks. We used structural equation modeling
      to test associations between the variables that were specified a priori. These
      analyses demonstrate the central role of BMI as a determinant of hip and knee
      flexion ROM. For an increase in level of BMI, the coefficients [SEM] for changes
      in levels of hip and knee ROM were -0.38 [0.05] and -0.26 [0.05], respectively. A
      higher BMI resulted in lower hip and knee ROM. BMI was also directly associated
      with prevalent diabetes (0.10 [0.05]) and arthritis (0.17 [0.05]). However, after
      adjustment for BMI, diabetes and arthritis did not have direct independent
      associations with either hip or knee ROM. BMI was also indirectly associated with
      knee, but not hip, ROM through paths including lower-leg pain, pain intensity,
      and neurosensory impairments. Diabetes had an indirect association with hip, but
      not knee ROM, through a path including peripheral vascular disease. In
      conclusion, BMI is a primary direct determinant of hip and knee ROM. The paths by
      which diabetes and arthritis lead to physical disability may be mediated, in
      part, at the level of impairment by BMI's association with joint range of motion.
      Interventions designed to decrease the impact of diabetes and arthritis on
      disability should track changes in BMI and joint ROM to measure the paths that
      account for the intervention's success. The observed associations suggest that
      interventions targeted to decrease BMI itself may lead to improved function in
      part through improved joint ROM.

PMID- 10965381
TI  - Detection of depressive symptomatology in elderly people: a short version of the
      CES-D scale.
AB  - This study aims to test a short form of the Center for Epidemiological Studies-
      Depression Scale (CES-D) which can be a useful screening tool for depressive
      symptomatology in epidemiological studies of elderly patients. The study was
      conducted on 2792 subjects from the PAQUID (Personnes Agees QUID?) cohort, an
      epidemiological survey of community dwellers living in South-West France. CES-D
      items with high sensitivity and good specificity were selected for the short
      form, then the best cut-off scores were determined with Receiver Operating
      Characteristics (ROC) curves. The external validity of the 5-item scale was then
      assessed against the full scale at different PAQUID follow-ups. Sensitivity was
      99% and specificity 81% for detecting depressive symptomatology when compared to
      the 20-item scale. The external validity on the different follow-ups was good,
      yielding a sensitivity varying from 95 to 100%, and a specificity from 83 to 89%.
      In conclusion, the 5-item CES-D is a simple, rapid and reliable tool which could
      be useful for screening depressive symptoms in epidemiological studies of the
      elderly.

PMID- 10965380
TI  - Using a criterion standard to validate the Alcohol-Related Problems Survey
      (ARPS): a screening measure to identify harmful and hazardous drinking in older
      persons.
AB  - We compared the Alcohol-Related Problems Survey (ARPS), a new screening measure
      targeted at harmful and hazardous drinking among older individuals, to a
      criterion standard (CS) among 22 persons aged 65 and older who reported consuming
      at least one drink of alcohol in the previous 12 months. The CS was conducted by
      a study physician and research assistant. It assessed risks from alcohol use, and
      consisted of a structured review of each subject's medical record, clinical
      interview, physical examination, and an interview with a collateral informant.
      Analyses included descriptive statistics for demographic and health
      characteristics, inter-rater reliability, agreement between the ARPS and the CS,
      reasons for disagreement, and sensitivity and specificity of the ARPS as compared
      to the CS. Using Landis and Koch criteria, inter-rater reliability between two
      physicians for 11 subjects was substantial (weighted kappa 0.79), but agreement
      between the ARPS and the CS was only fair (weighted kappa 0.28). Reasons for
      disagreement included problems with ARPS' questions and classification rules, and
      problems with study physicians' assessments of drinking risk. Based on these
      reasons for disagreement, we made revisions in the ARPS and its classification
      rules. Agreement between the revised ARPS and the CS improved substantially
      (weighted kappa 0.62). Sensitivity and specificity of the original ARPS were 80%
      and 50%, respectively, and both improved to 82% after revisions. The revised ARPS
      is sensitive and specific for identifying harmful and hazardous drinking in older
      persons as determined by clinicians.

PMID- 10965382
TI  - Psychotropic drug use, falls and hip fracture in the elderly.
AB  - The use of benzodiazepines (BZD) or other psychotropic agents is an established
      risk factor for falls and hip fractures. The evidence supporting this association
      has been based solely on history and/or prescription data. In a case-control
      study we monitored the intake of BZD, tricyclic antidepressants (TCA) and
      barbiturates in patients with hip fracture by serum analysis, and compared this
      measurement with drug history and prescription records. The serum was BZD
      positive in 41% of 82 community-dwelling patients; an equivalent by history
      and/or prescription records, however, was detected in only 18% (p < 0.0001). In
      contrast, in 82 age- and gender-matched community-dwelling control patients,
      there was only a minor discrepancy (3%) in BZD use between anamnestic (N = 19)
      and analytical (N = 21) data. In 23 patients admitted from nursing homes, a
      similar trend was visible (39% serum positive for BZD vs 26% by drug history).
      Barbiturate use (N = 2) could be neglected, and TCA intake was minor (N = 7); in
      each case both assessments were in accordance. In conclusion, in patients with
      hip fracture, BZD use is substantially more frequent than reported and previously
      assumed, pointing to an underestimated risk factor for this injury.

PMID- 10965383
TI  - Awareness, attitudes and opinions on osteoporosis of primary care physicians
      working in the metropolitan area of Rome: a brief report.
AB  - Attitudes of primary care physicians towards prevention, diagnosis and treatment
      of osteoporosis have important implications in clinical practice; however, in
      Italy, this issue has been poorly investigated. This study aimed to determine
      whether the awareness and opinions of family physicians regarding the management
      of osteoporosis are in line with the suggestions of experts in the field. One
      hundred of 115 randomly selected family physicians from the area of Rome were
      asked to participate, and completed a survey on osteoporosis including ten close
      ended questions. Response rates documented the degree of awareness about
      osteoporosis. Thirty-six percent of physicians make the diagnosis of osteoporosis
      based exclusively on bone densitometry (BD), while 17% never utilize BD. Fifty
      three percent of doctors assess biochemical markers of bone turnover, but half of
      them are unaware of the existence of more sensitive and specific markers. Forty
      four percent of physicians autonomously start therapy according to the
      suggestions of journal reports (38%), and/or pharmaceutical advertisements (18%).
      Regarding treatment follow-up, 60% of doctors gave inadequate answers, as 25% and
      35% of them check bone markers after six months of therapy, and BD within one
      year of therapy initiation, respectively. In conclusion, experts on osteoporosis
      should give more attention to the education of primary care physicians regarding
      the management of the disease.

PMID- 10965384
TI  - Neighborhood disorder, fear, and mistrust: the buffering role of social ties with
      neighbors.
AB  - This paper proposes that individuals who report that they live in neighborhoods
      characterized by disorder--by crime, vandalism, graffiti, danger, noise, dirt,
      and drugs--have high levels of fear and mistrust. It further proposes that an
      individual's alliances and connections with neighbors can buffer the negative
      effects of living in a neighborhood characterized by disorder on fear and
      mistrust. Results from a representative sample of 2482 Illinois residents
      collected by telephone in 1995 support the propositions. Living in a neighborhood
      with a lot of perceived disorder significantly affects mistrust and the fear of
      victimization, adjusting for sociodemographic characteristics. Perceived
      neighborhood disorder and social ties significantly interact: informal social
      ties with neighbors reduce the fear- and mistrust-producing effects of disorder.
      However, formal participation in neighborhood organizations shows little
      buffering effect.

PMID- 10965385
TI  - Coping, conflictual social interactions, social support, and mood among HIV
      infected persons. HCSUS Consortium.
AB  - This study considers the interrelationships among coping, conflictual social
      interactions, and social support, as well as their combined associations with
      positive and negative mood. Research has shown that each of these variables
      affects adjustment to stressful circumstances. Few studies, however, examine this
      full set of variables simultaneously. One hundred forty HIV-infected persons
      completed a questionnaire containing measures of coping, social support,
      conflictual social interactions, and positive and negative mood. Factor analyses
      showed that perceived social support and conflictual social interactions formed
      separate factors and were not strongly related. Compared to perceived social
      support, social conflict was more strongly related to coping behaviors,
      especially to social isolation, anger, and wishful thinking. Conflictual social
      interactions were more strongly related to negative mood than was perceived
      social support. Coping by withdrawing socially was significantly related to less
      positive and greater negative mood. The findings point to the importance of
      simultaneously considering coping, supportive relationships, and conflictual
      relationships in studies of adjustment to chronic illness. In particular, a
      dynamic may occur in which conflictual social interactions and social isolation
      aggravate each other and result in escalating psychological distress.

PMID- 10965386
TI  - A cost analysis of self-management programs for people with chronic illness.
AB  - The soaring cost of health care is a national problem that needs response at
      multiple levels, including that of the community. Reducing or limiting health
      care costs through interventions that emphasize the self-management of health may
      promote broader health care coverage, better quality of health care, and a sense
      of control over one's health. Therefore, it behooves community psychologists to
      perform cost analyses when testing interventions for people in a community. The
      present study investigated the effects of social support and education
      interventions on psychosocial variables, health status, and health care costs in
      older people with osteoarthritis. Participants were 363 members of a health
      maintenance organization (HMO), 60 years of age and older, with osteoarthritis.
      Participants were randomly assigned to one of three intervention groups (social
      support, education, or a combination of both) or to a control group. The results
      indicated that feelings of helplessness decreased in the intervention groups but
      not in the control group. All groups showed increases in self-efficacy and
      overall health status. In addition, health care costs increased less in the
      intervention groups than in the control group. Cost analysis was used to
      demonstrate that the monetary savings of the intervention greatly outweighed the
      cost of conducting the intervention. It appears that interventions can limit
      health care costs while improving health and increasing feelings of control for
      older people with osteoarthritis. Further, this paper demonstrates how a cost
      benefit focus can benefit community studies.

PMID- 10965387
TI  - Moving beyond the illness: factors contributing to gaining and maintaining
      employment.
AB  - The work presented here, exploratory in nature, uses a comparative and
      qualitative approach to understand the factors associated with the ability of
      individuals with severe and persistent mental illness to successfully gain and
      maintain employment. Based on open-ended interviews with individuals in an
      Assertive Community Treatment (ACT) program, we compare the experiences of those
      who have been successful gaining and maintaining employment, with those who have
      been successful gaining but not maintaining work, and those who have been
      unsuccessful gaining employment. The three groups seemed to differ in three
      significant ways: (1) in the ways the individuals talked about their illness, (2)
      in the ways the individuals talked about work, and (3) in the strategies they
      described for coping with bad days. In each of these areas individuals' awareness
      of and attitude toward their illness was significant. The findings have clear
      implications for agencies working to help people with severe and persistent
      mental illness obtain and maintain employment.

PMID- 10965388
TI  - Natural disaster and depression: a prospective investigation of reactions to the
      1993 midwest floods.
AB  - A statewide sample of 1735 Iowa residents, approximately half of whom were
      victims of the 1993 Midwest Floods, participated in interviews 1 year prior to,
      and 30 to 90 days after, the disaster. Employing a rigorous methodology including
      both control-group comparisons and predisaster assessments, we performed a
      systematic evaluation of the disaster's impact. Overall, the disaster led to true
      but small rises in depressive symptoms and diagnoses 60-90 days postflood. The
      disaster-psychopathology effect was not moderated by predisaster depressive
      symptoms or diagnostically defined depression; rather, predisaster symptoms and
      diagnoses uniquely contributed to increases in postdisaster distress. However,
      increases in symptoms as a function of flood impact were slightly greater among
      respondents with the lowest incomes and among residents living in small rural
      communities, as opposed to on farms or in cities. Implications for individual-
      and community-level disaster response are discussed.

PMID- 10965389
TI  - A longitudinal examination of the transition into senior high school for
      adolescents from urban, low-income status, and predominantly minority
      backgrounds.
AB  - The current 6-year study investigates the impact of the elementary (K-8)-to-high
      school (9-12) transition on the school completion outcomes of 107 adolescents
      from urban, minority, low-income status backgrounds. Descriptive findings provide
      a longitudinal profile of students' enrollment status throughout high school.
      Students who had graduated or were Active in the school system at the end of the
      study evidenced more marked change in perceptions of social support following the
      transition to the ninth grade compared to Inactive students, dropouts, who
      evidenced little change. With respect to academic performance, while both groups
      evidenced declines following the transition and failed to recover sustained
      losses, Inactive students declined more sharply in grades and attendance.
      Findings are discussed in terms of the mixed support for the transitional life
      events perspective. In addition, study limitations and directions for future
      research are discussed, including variables that should be considered in research
      with the targeted group.

PMID- 10965390
TI  - Help-seeking comfort and receiving social support: the role of ethnicity and
      context of need.
AB  - Examined help-seeking comfort and receiving social support among Latinos, African
      Americans, and European Americans across two contexts: in a communitywide
      emergency (Hurricane Andrew) and 2 years later in a nonemergency situation. In
      general, help-seeking comfort was a strong predictor of received support.
      Notwithstanding many similarities between the groups, the effects of ethnicity
      differed according to the context. In emergency, all groups reported similarly
      high levels of help-seeking comfort and received support. In nonemergency, help
      seeking comfort declined for blacks and whites but not for Latinos. Although all
      ethnic groups reported receiving less social support in nonemergency, the decline
      in received support across contexts was most dramatic for Latinos. Situational,
      cultural, and differential resource loss explanations are offered to account for
      the findings.

PMID- 10965391
TI  - Advisory committees oppose nonprescription status for 'statins'.

PMID- 10965392
TI  - Think globally about resistance, says WHO.

PMID- 10965394
TI  - Harvey A. K. Whitney Lecture. Initiatives for reducing medication errors: the
      time is now.

PMID- 10965393
TI  - Linezolid, Alosetron, Levetiracetam.

PMID- 10965395
TI  - Pharmacokinetics of promethazine hydrochloride after administration of rectal
      suppositories and oral syrup to healthy subjects.
AB  - The pharmacokinetics of promethazine hydrochloride after administration of rectal
      suppositories at three dosage strengths and oral syrup were studied. The study
      had an open-label, randomized, crossover design. At intervals of five to nine
      days, healthy volunteers were given two 12.5-mg promethazine rectal
      suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of
      promethazine oral syrup. Blood samples were collected before each dose and at
      intervals from 0.5 to 48 hours afterward. Promethazine concentration was
      determined by high-performance liquid chromatography, and pharmacokinetic values
      were calculated with noncompartmental methods. Thirty-six subjects (18 men and 18
      women) completed the study. Absorption was highly variable for all the
      formulations. On average, absorption was more rapid and the maximum plasma
      concentration (Cmax) higher for the syrup than for the suppositories. Cmax was
      significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the
      syrup (19.3 ng/mL). The time to Cmax (tmax) was significantly shorter for the
      syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours). There were no
      significant differences in dose-normalized Cmax among the three suppository
      treatments. Area under the concentration-versus-time curve (AUC) was comparable
      between the syrup and the 50-mg suppository and between the treatments with two
      12.5-mg suppositories and the 25-mg suppository. Elimination profiles were
      similar among all treatments (mean half-life [t1/2], 16-19 hours). There were no
      significant differences in pharmacokinetics on the basis of sex or race. The mean
      relative bioavailability for the three suppository treatments ranged from 70% to
      97%. Individual relative bioavailabilities ranged from 4% to 343%. The
      pharmacokinetics of promethazine administered in oral syrup and rectal
      suppositories were highly variable, but, in general, the suppositories produced a
      lower Cmax and later tmax than the syrup. All formulations were comparable in
      terms of dose-normalized AUC and t1/2, and the three suppository treatments were
      comparable in terms of dose-normalized Cmax.

PMID- 10965396
TI  - Changing physician prescribing behavior: the community-acquired pneumonia
      intervention trial.
AB  - The Notes section welcomes the following types of contributions: (1) practical
      innovations or solutions to everyday practice problems, (2) substantial updates
      or elaborations on work previously published by the same authors, (3) important
      confirmations of research findings previously published by others, and (4) short
      research reports, including practice surveys, of modest scope or interest. Notes
      should be submitted with AJHP's manuscript checklist. The text should be concise,
      and the number of references, tables, and figures should be limited.

PMID- 10965397
TI  - ASHP statement on reporting medical errors.

PMID- 10965398
TI  - Dolasetron-associated venous irritation.

PMID- 10965400
TI  - Insulin-free World Foundation.

PMID- 10965399
TI  - Tolcapone: more than meets the eye?

PMID- 10965401
TI  - Needle-free injection technology.

PMID- 10965402
TI  - Microvessel quantitation in intraductal and early invasive breast carcinomas.
AB  - OBJECTIVE: To study the angiogenic process in intraductal carcinoma of the
      breast, with and without a small focus of stromal infiltration, and to compare
      the microvessel density between the in situ phase and the early infiltration
      phases of breast cancer. STUDY DESIGN: Microvessel density (number of
      microvessels per square millimeter of neoplasia) was quantitatively evaluated on
      anti-factor VIII-immunostained histologic sections obtained from 10 ductal
      carcinomas in situ (DCIS) (category A), 22 DCIS with a small focus of stromal
      infiltration (category B), 10 microinvasive carcinomas (category C), 12 T1a
      carcinomas (category D) and 20 T1b carcinomas (category E). RESULTS: The five
      categories of lesion had different values for microvessel density (P = .0017).
      Category A had microvessel density lower than category B (P = .0005). Category B
      had microvessel density higher than categories C, D and E (P = .0028, .0133 and
      .0033, respectively). CONCLUSION: Microvessel density seems to be a feature
      related to each crucial step in the early phases of neoplastic progression.

PMID- 10965403
TI  - Morphometric analysis of renal vessels. Advantage of the multisector area
      approach to cross-sections.
AB  - OBJECTIVE: To determine the most accurate morphometric approach to overcoming the
      obstacles of limited number, angle of section and irregular contours of vascular
      structures in analyzing vascular sections of renal biopsies. STUDY DESIGN: The
      luminal area of 451 cortical arterioles in 65 Masson-trichrome-stained renal
      sections was assessed with a computer-assisted imaging system connected to a
      Leica DMR microscope (Mikroskopie und Systeme GmbH, Wetzlar, Germany). The
      luminal area measured by the imaging system was used as the gold standard,
      against which three mathematical sector approaches and one classical approach
      were evaluated. The accuracy of these approaches was evaluated by means of the
      relative deviation from the measured value and of the degree of overestimation or
      underestimation. Intraobserver and interobserver variability were determined for
      the most accurate mathematical approach. RESULTS: As compared to measured luminal
      area, the sector elliptical approach yielded the lowest relative deviation (13.4
      +/- 12.5%), without significant overestimation or underestimation (-0.6 +/-
      18.3%). The intraobserver and interobserver correlation coefficients for this
      method were 82.3% and 86.5%, respectively. CONCLUSION: The sector elliptical
      approach is the most accurate mathematical approach to vascular sections in renal
      biopsies.

PMID- 10965404
TI  - Nuclear size and shape in fine needle aspiration biopsy samples of the prostate.
AB  - OBJECTIVE: To study the potential of nuclear size and shape estimates in
      interpreting fine needle aspiration biopsy (FNAB) samples of the prostate. STUDY
      DESIGN: Morphometry was used to outline nuclei of prostate cells. Cell groups
      were selected by an experienced cytologist. RESULTS: The mean area of nuclei in
      the most atypical cell groups among definitely malignant samples (n = 17) varied
      from 26.3 to 93.3 micron 2 and in normal prostate cells (n = 10) from 15.6 to
      33.7 micron 2. Perfect distinction of definitely benign and slightly atypical
      samples (n = 13) from definitely malignant samples was possible when the samples
      were characterized by the weighted means of the mean nuclear areas of the cell
      groups in the samples. The means of individual cell groups allowed correct
      distinction in only 84.8% of cell groups. Shape factors did not have any
      diagnostic value. CONCLUSION: Morphometric nuclear size estimates from ethanol
      fixed FNAB samples of the prostate are of diagnostic value and can potentially be
      used as part of multivariate diagnostic models when selected by an experienced
      cytologist according to strict criteria. However, measurement should be done from
      several cell groups (at least three of the most-atypical cell groups) in each
      sample.

PMID- 10965405
TI  - Diagnostic assessment of cutaneous melanoma and common nevi using tissue counter
      analysis.
AB  - OBJECTIVE: To test the applicability of tissue counter analysis to the diagnostic
      discrimination of cutaneous malignant melanoma and benign common melanocytic
      nevi. STUDY DESIGN: Forty cases each of melanoma and nevi were consecutively
      sampled. After creation of a learning set based on 20 cases each, discriminant
      analysis of background versus tissue elements, tumor versus other tissue elements
      and benign versus malignant tumor elements was performed. The discriminant
      functions were used to assess the amount of benign and malignant tumor elements
      in each case. RESULTS: In the learning set, discriminant analysis facilitated
      recognition of 99.6% of tissue versus background, 90.7% of tumor versus other
      tissue components and 85.6% of malignant versus benign tumor elements. In the
      whole set, the percentage of malignant tumor elements was 8.7 +/- 7.7 (range, 0.1
      29.6) for benign nevi and 77.4 +/- 16.2 (43.6-99.4) for malignant melanoma. Based
      on these measurements, the correct diagnosis could be established in all cases
      (chi 2 > .0001). CONCLUSION: Tissue counter analysis may be a useful method for
      diagnostic purposes in histopathology.

PMID- 10965406
TI  - Correlation between apoptotic figure counting and the TUNEL technique.
AB  - OBJECTIVE: To compare histologic detection of apoptotic (AP) figures and terminal
      transferase UTP nick end labeling (TUNEL) detection in colorectal carcinomas and
      lymphomas. STUDY DESIGN: We evaluated the percentage of AP cells by AP figure
      counting and by the TUNEL technique in formalin-paraffin material from 39 tumors-
      29 colorectal carcinomas and 10 non-Hodgkin's lymphomas. The Lucia G image
      analysis system (Laboratory Imaging, Prague, Czech Republic) was used for
      cellularity evaluation and AP counting. RESULTS: On average, 0.81 +/- 0.5% AP
      cells were detected by figure counting; 0.91 +/- 0.35% were identified by TUNEL.
      A statistically high correlation between these techniques was found using
      Pearson's correlation coefficient (r = .56, P < .001). TUNEL, although probably
      more sensitive, was difficult to standardize. CONCLUSION: AP figure counting
      seems to be the method of choice for routine work, particularly because of its
      cost effectiveness and reproducibility.

PMID- 10965407
TI  - Segmentation of color images from serous cytology for automated cell
      classification.
AB  - OBJECTIVE: To design an automated system for the classification of cells based on
      analysis of serous cytology, with the aim of segmenting both cytoplasm and
      nucleus using color information from the images as the main characteristic of the
      cells. STUDY DESIGN: The segmentation strategy uses color information coupled
      with mathematical morphology tools, such as watersheds. Cytoplasm and nuclei of
      all diagnostic cells are retained; erythrocytes and debris are eliminated.
      Special techniques are used for the separation of clustered cells. RESULTS: A
      large set of cells was assessed by experts to score the segmentation success
      rate. All cells were segmented whatever their spatial configurations. The average
      success rate was 92.5% for nuclei and 91.1% for cytoplasm. CONCLUSION: This color
      information-based segmentation of images of serous cells is accurate and provides
      a useful tool. This segmentation strategy will improve the automated
      classification of cells.

PMID- 10965408
TI  - Computerized morphometric study on fine needle aspirates of cellular follicular
      lesions of the thyroid.
AB  - OBJECTIVE: To investigate the value of computerized nuclear morphometry in the
      differential diagnosis of cellular follicular lesions of the thyroid
      cytologically diagnosed on fine needle aspiration (FNA) smears. STUDY DESIGN:
      Sixty cases of FNA thyroid smears were cytologically diagnosed and classified as
      follows: 30 cases of follicular carcinoma, 20 cases of cellular hyperplastic
      nodules and 10 cases of follicular adenoma. Using an image analysis system, two
      morphometric variables, nuclear area and major axis length of the nucleus, were
      measured for each case. RESULTS: For both nuclear morphometric variables,
      statistical differences were found between carcinomas and hyperplastic nodules as
      well as between carcinomas and adenomas. No statistical differences were found
      between the nuclear variables in either hyperplastic nodules or adenomas.
      CONCLUSION: The results confirm the aim of our study, to establish nuclear
      morphometry by computerized image analysis as an additional tool in the
      differential diagnosis of thyroid follicular lesions cytologically diagnosed on
      FNA smears.

PMID- 10965409
TI  - Reliable differential diagnosis between osteosarcoma and regenerative bone cells
      in rats through simultaneous analysis of nuclear DNA content and size.
AB  - OBJECTIVE: To evaluate the difference between benign proliferative lesions of
      regenerative bone calluses and malignant tumors in rats by simultaneous analysis
      of nuclear DNA content and size. STUDY DESIGN: Nuclei were stained with DAPI and
      measured by cytofluorometry. Five regenerative bones and five osteosarcoma
      samples were used. Two-dimensional dispersion diagrams between relative nuclear
      DNA content and nuclear size were drawn up and their regression lines were
      compared. RESULTS: It was possible to distinguish between osteosarcomas and
      regenerative bones by simultaneous analysis of nuclear size and DNA content
      during the cell cycle. The results yielded coefficients of correlation and
      regression. All five regression lines of osteosarcomas were situated dramatically
      higher on dispersiongrams than those of regenerative bones. CONCLUSION:
      Differential diagnosis between regenerative lesions and malignant tumors may now
      be possible using simultaneous measurement of nuclear DNA content and size.

PMID- 10965410
TI  - Predictive value of DNA cytometry in CIN 1 and 2. Image analysis of 193 cases.
AB  - OBJECTIVE: To investigate DNA image cytometry for predicting the prognosis of
      cervical intraepithelial neoplasia (CIN). STUDY DESIGN: Smears from 151 women
      affected by CIN 1 or 2 on cytology with minimal follow-up of three years were
      included. Sixty-seven showed progression, with histologically confirmed carcinoma
      in situ or invasive cancer. Eighty-four cases showed regression of the disease,
      which was cytologically, histologically and colposcopically confirmed.
      Papanicolaou-stained smears were destained, and the Feulgen reaction was
      performed with consecutive image DNA cytometry of suspicious cells using an image
      analysis system (Cires, Zeiss, Germany). The DNA index of the greatest stemline
      and the number of single aneuploid cells, using 9c exceeding events, were
      computed. RESULTS: In the group with progression, an aneuploid DNA stemline was
      found in 25 smears (26.9%). In 64 cases (66.7%) more than one aneuploid event was
      detected. The total number of aneuploid cases in this group was 76 (81%). In the
      group without progression, the number of aneuploid stemlines was 2 (2%). Single
      aneuploid cells could be found in five cases (5%). The overall number of
      aneuploid cases in that group was five. The sensitivity was 74.3%, positive
      predictive value 85.2% and negative predictive value 77%. CONCLUSION: Aneuploidy
      is a marker for prospective malignancy in cervical Papanicolaou smears. DNA image
      cytometry, as an additional method, can be used to predict outcome in patients
      with CIN 1 and 2 of the cervix. DNA cytometry is not a screening method but can
      add further information for a treatment decision in doubtful cases.

PMID- 10965412
TI  - Gradient of nuclear volume changes in breast cancer and its relation to
      prognosis.
AB  - OBJECTIVE: In a study of 112 cases of invasive breast cancer, the prognostic
      value of the gradient of nuclear volume (NV) changes was examined. STUDY DESIGN:
      On conventional histologic slides of surgically resected specimens, we studied
      the nuclear changes from early to advanced. The former was represented by the
      noninvasive area in the tumor periphery and the latter by the invasive area with
      true neoplastic stroma. We analyzed the difference in NV between the noninvasive
      area in the tumor periphery (NVcis) and the invasive area where the nuclei are
      large (NVlarge), a zone we assessed to have the greatest cancer progression.
      Based on these measurements, we defined NV gradient index (NVG index) as the
      ratio of NVlarge to NVcis. RESULTS: The NVG index in cases of cancer death (4.33
      +/- 1.70, n = 35) was significantly larger than in relapsing survivors (2.76 +/-
      1.31, n = 13, P = .002) and in relapse-free survivors (2.17 +/- 1.60, n = 64, P <
      .0003). In the group of cancer deaths, the correlation coefficient between NVG
      index and survival was -0.398 (0 < P < .02). Even in cases of stage I, NVG index
      in the group of cancer deaths (5.68 +/- 1.4) was significantly larger than in
      relapsing survivors (2.42 +/- 1.2) or relapse-free survivors (1.74 +/- 0.55). By
      multivariate analysis, NVG index was independently prognostic for disease
      specific survival (P = .0001). CONCLUSION: The NVG index contributes to
      discrimination between possible survivors and cancer deaths. Though there are
      exceptions, cases with a small NVG index can be expected to survive for a longer
      period even after a relapse.

PMID- 10965411
TI  - Image analysis of mesothelioma. II. Discrimination of mesothelioma from
      metastatic serous ovarian adenocarcinoma.
AB  - OBJECTIVE: To examine the utility of karyometric measurements in the
      differentiation of mesothelioma from metastatic serous ovarian adenocarcinoma.
      STUDY DESIGN: High-resolution images of 1,631 nuclei from 32 cases of
      mesothelioma and 742 nuclei from 15 cases of ovarian adenocarcinoma were
      recorded. A stepwise discriminant analysis and nonparametric classifier were
      applied. RESULTS: Nuclei from these two diagnostic categories appear very similar
      and occupy feature space with significant overlap. A nonparametric classification
      procedure provided acceptable correct classification. CONCLUSION: For certain
      regions in feature space, cases could be unequivocally classified.

PMID- 10965413
TI  - American Society of Cytopathology statement on new technologies in cervical
      cytology screening. June 2000.

PMID- 10965414
TI  - Study on the interaction of the dopamine agonist alpha-dihydroergocryptine with
      the pharmacokinetics of digoxin.
AB  - AIM: The study was carried out to explore the potential for pharmacokinetic
      interaction of a single oral dose of alpha-dihydroergocryptine (CAS 14271-05-7,
      DHEC, Almirid) with digoxin. METHODS: The serum pharmacokinetics of digoxin were
      analysed after the administration of single oral doses of 0.5 mg digoxin
      administered either alone or concomitantly with 20 mg DHEC according to a
      randomised, non-blinded, two-period cross-over design, with study periods 2 weeks
      apart. Twelve healthy male subjects, 23 to 39 years of age were enrolled and were
      investigated in accordance with the protocol. Venous blood was sampled up to 48 h
      after dosing. Concentrations of digoxin in serum were determined by a competitive
      radioimmunoassay. RESULTS: The mean Cmax were 1.97 +/- 0.87 (after a median tmax
      of 1 h) and 2.05 +/- 0.95 ng/ml (after a median tmax of 0.83 h) after the
      administration of digoxin with (test) and without (reference) concomitant DHEC,
      respectively; the corresponding estimated treatment ratio for test: reference was
      0.939, 95% CI: 0.781 to 1.129. The mean AUC(0-48) were 13.6 +/- 5.0 ng.h/ml and
      13.3 +/- 4.7 ng.h/ml for the test and reference treatment, respectively; the
      corresponding estimated treatment ratio for test: reference was 1.011, 95% CI:
      0.866 to 1.142. In addition, no clinically significant changes were observed by
      ECG monitoring. The tolerability of digoxin alone was good, significantly more
      adverse events occurred when co-administered with DHEC; these corresponded with
      the known adverse reaction profile and were of moderate intensity. No premature
      study termination was thus necessary. CONCLUSION: The present study did not
      demonstrate clinically relevant interaction of a single dose of DHEC on the
      pharmacokinetics of digoxin. On the basis of these observations there is no
      indication for an a priori adjustment of the dose of digoxin when concomitant
      treatment with DHEC is initiated.

PMID- 10965415
TI  - Effects of intravenous azimilide on cardiac performance, fibrillation threshold,
      and hemodynamics in anesthetized dogs.
AB  - The class III antiarrhythmic azimilide (E-1-[[[5-(4-chlorophenyl)-2
      furanyl]methylene]-amino]-3-[4-(4-methyl-1- piperazinyl)butyl]-2,4
      imidazolidinedione dihydrochloride; WHO No. 7299, CAS 149888-94-8), by slow
      infusion or stepwise bolus doses, was evaluated for effects on heart rate, blood
      pressure, and cardiac pump function, excitability, and refractoriness in
      anesthetized dogs. Infusion (0.6 mg/kg/min) in male beagles (n = 5) to a maximum
      dose of 54 mg/kg increased QTc more than 20 ms at 2.0 mg/kg. At a dose of 8.9
      mg/kg i.v., QTc increased 34% above baseline and remained elevated throughout the
      subsequent infusion and for at least 60 min postinfusion. At this maximum class
      III dose, azimilide increased heart contractile force (HCF) 10% and +dP/dt 34%
      and decreased heart rate (HR) 12%, without significantly changing mean blood
      pressure (MBP), left ventricular end diastolic pressure, -dP/dt, stroke volume
      (SV), or cardiac output (CO). At the mean maximum 47 mg/kg i.v. dose, QTc
      remained elevated, but decreases were observed in HCF (-27%), +dP/dt (-24%), 
      dP/dt (-35%), SV (-16%), and CO (-52%). Cumulative intravenous bolus injections
      of azimilide (0.3, 1, 3, 10, and 30 mg/kg) in male mongrels (n = 5) increased
      effective refractory period (ERP) and +dP/dt (18% and 16%, respectively, at 10
      mg/kg) as a function of dose and significantly decreased HR (-22% at 10 mg/kg).
      MBP decreased significantly (-23%) only at the highest dose. Ventricular
      fibrillation threshold (VFT) was unchanged at 30 mg/kg. Effects of dl- (n = 3)
      and d-sotalol (n = 4) on ERP and HR were similar to azimilide's, but both
      compounds caused a greater MBP depression and VFT elevation. These results
      suggest that azimilide is well tolerated by the cardiovascular system, providing
      an increase in contractility and a slight decrease in HR at intravenous doses
      that produced a large or maximum increase in cardiac refractoriness.

PMID- 10965416
TI  - Acute effect of a dried ethanol-water extract of garlic on the microhaemovascular
      system of the skin.
AB  - In the present study, the acute vasoactive effect of a dried hydrophilic extract
      of garlic with 600 mg active substance (Alliosan) was investigated in 10 healthy
      volunteers. Laser-Doppler fluxmetry, video capillary microscopy and
      transcutaneous partial pressure of oxygen measurements were used for the
      objective assessment of functional and morphological parameters. An increase in
      perfusion could be demonstrated by these means. This was based on an increase in
      erythrocyte flow velocity of up to 2 h duration, which was mainly due to
      vasodilation in both arterial and venous vessels. A change in transcutaneous
      partial pressure of oxygen or an influence on sympathetically-mediated vasomotor
      reflexes could not be demonstrated. Furthermore, there was no evidence of an
      influence on reactive hyperaemia after controlled hyperthermia. The test
      substance was shown to increase the cutaneous microperfusion.

PMID- 10965417
TI  - [Effects of an herbal crataegus-camphor combination on the symptoms of
      cardiovascular diseases].
AB  - One hundred and ninety (190) patients presenting with "functional cardiovascular
      disorders" (ICD 10, F 45.3) received purely herbal combination therapy comprising
      crataegus and camphor (Korodin Herz-Kreislauf-Tropfen) or a placebo, identical in
      colour and taste to the active treatment, over a period of four weeks within the
      scope of a multi-centre, placebo-controlled, double-blind study. The principal
      criterion was the fall in the overall score obtained for a heart-related symptom
      complex (HSK) during administration of the herbal combination or randomly
      allocated placebo. The overall score fell significantly by 5.5 or 4.5 points,
      respectively, from a baseline value of 10.0 points each (p = 0.0165). The sub
      score for exhaustion, joint pain, heart disorders, pain on pressure and the total
      score on the Giessen discomfort chart (GBB) indicated better efficacy with the
      crataegus-camphor combination than with the placebo. On completion of treatment,
      the investigators assessed the efficacy of the active drug as "very good to good"
      in 70.5% of their patients compared with a similar evaluation in just 49.5% of
      the placebo patients. The degree of satisfaction with the drug therapy according
      to physician and patient reflected the objective results obtained. 71.6% of
      subjects in the active drug group were satisfied with their treatment compared
      with just 52.7% in the placebo group. Adverse events (undesirable side effects)
      were recorded in 8.3% and 8.5% of patients, respectively. A correlation with the
      active drug therapy was established in only two cases. Tolerance was therefore
      positively assessed.

PMID- 10965419
TI  - Synthesis and hypoglycemic activity of some new flavone derivatives. 3rd
      communication: 3'-flavonyl-2,4-thiazolidinediones.
AB  - A new series of 3'-flavonyl-2,4-thiazolidinedione, 2,4-imidazolidinedione and 2
      thiohydantoin derivatives (1-10) were synthesized and their chemical structures
      have been elucidated by various spectral data. The prepared compounds were tested
      for their insulinotropic effects in INS-1 cells. Inhibitory effects were observed
      for compounds 1 and 2. In contrast compounds 4, 7 and 8 were able to increase
      insulin release compared with glibenclamide.

PMID- 10965418
TI  - Effect of the calcium antagonist benidipine hydrochloride on 24-h ambulatory
      blood pressure in patients with mild to moderate hypertension in a double-blind
      study against placebo.
AB  - The effects of benidipine hydrochloride (benidipine, CAS 91559-74-5), a
      dihydropyridine calcium antagonist, on the 24-h ambulatory blood pressure were
      studied by a double-blind test against placebo in 8 patients with essential
      hypertension. The mean resting systolic (SBP) and diastolic (DBP) blood pressures
      were 173 mmHg and 104 mmHg, respectively, at the time of patients enrollment.
      Blood pressure was measured every 30 min for 24 h after a single oral
      administration of either benidipine (4 mg/day) or the placebo. The mean
      through/peak (T/P) ratios were calculated from blood pressure measurements
      obtained using 2-h moving averages, and the smoothness index (SI) was calculated
      by subtracting the effect of the placebo from that of benidipine at each
      interval. The mean SBP and DBP fell to 135 and 88 mmHg, respectively, after
      dosing, which gave T/P ratios of 82% and 64%, respectively. The SIs for SBP and
      DBP were 1.82 and 0.76, respectively. These findings indicate that benidipine
      maintained a satisfactory and durable antihypertensive effect by once-a-day
      dosing.

PMID- 10965420
TI  - New diaminoether coumarinic derivatives with anti-inflammatory activity.
AB  - Four coumarinyl-oxy-diamines were synthesized and tested as anti-inflammatory
      agents. pKa and log P were theoretically calculated. These compounds were tested
      for their ability to interact with 1,1-diphenyl-2-picrylhydrazyl stable free
      radical (DPPH), to inhibit proteolysis and soybean lipoxygenase (LOX) in vitro.
      They were found to inhibit proteolysis (82-90%) and soybean lipoxygenase activity
      (52-79%) very significant. On the contrary, their reducing ability was found to
      be low (8-22%). The effect of the synthesised compounds on inflammation using the
      carageenan-induced rat paw oedema model was studied. They showed a potent
      inhibitory effect on inflammation (37-55%). Both anti-inflammatory and
      antioxidant activities depended on some structural characteristics of the
      synthesised compounds.

PMID- 10965421
TI  - Bioequivalence study of tramadol by intramuscular administration in healthy
      volunteers.
AB  - Tramadol hydrochloride (CAS 36282-47-0) is a centrally acting analgesic agent
      binding to mu opiate receptors. The bioavailability of a new tramadol
      hydrochloride injection (Limadol) was compared with a commercially available
      reference product by intramuscular administration in twelve healthy Chinese male
      volunteers by a standard two-way cross-over trial. Each volunteer received a
      single 100 mg injection of tramadol HCl in each phase. The bioavailability was
      compared using the area under the plasma concentration-time curve from time 0 to
      30 h (AUC0-30), the area under the plasma concentration-time curve from time 0 to
      infinity (AUC0-infinity), peak plasma concentration (Cmax), and time to reach
      peak plasma concentration (Tmax). No statistically significant difference was
      observed between the Tmax, Cmax, AUC0-30 and AUC0-infinity of the two
      preparations. It is concluded that test and reference formulations of tramadol
      hydrochloride are bioequivalent for both the extent and rate of absorption after
      a single intramuscular injection.

PMID- 10965422
TI  - Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC.
AB  - A simple and sensitive HPLC method has been developed to measure trimebutine (CAS
      39133-31-8, maleate: CAS 34140-59-5) and its main metabolite desmethyl
      trimebutine in human plasma. The method was validated according to the Washington
      Consensus Conference on the Validation of Analytical Methods. It involved
      extraction of the plasma with n-hexane containing 2-pentanol, followed by
      reversed-phase HPLC using a Partisil ODS2 10 microns column and UV detection at
      265 nm. The retention times of the internal standard (procaine), desmethyl
      trimebutine and trimebutine were 2.4, 4.3 and 6.5 min, respectively. The standard
      curves were linear from 20 ng.ml-1 (limit of quantitation) to 5000 ng.ml-1 for
      both compounds. The coefficient of variation for all the criteria of validation
      were less than 15%. The extraction recoveries obtained for trimebutine and
      desmethyl-trimebutine were about 90%. Both compounds were very stable upon
      storage in plasma. The method was tested by measuring the plasma concentrations
      following oral administration to humans during a bioequivalence study and was
      shown suitable for pharmacokinetic studies.

PMID- 10965423
TI  - Polysaccharides from fresh Viscum album L. berry extract and their interaction
      with Viscum album agglutinin I.
AB  - A special microfiltrated colloidal preparation from fresh Viscum album L. berries
      was investigated concerning the occurrence and structural features of polymeric
      carbohydrates. A crude polysaccharide fraction was isolated from lectin-, tannin-
      and protein-depleted microfiltrates. Further fractionation by exchange
      chromatography revealed a neutral fraction (average molecular weight 30 kDa) and
      three acidic fractions (average molecular weights 1300 kDa). Structural analysis
      of the respective polysaccharide fractions by quantitative and qualitative
      determination of the sugar composition and linkage analysis indicated that all
      acidic fractions contained an acidic arabinogalactan with a rhamnose-galactoronic
      acid backbone and highly branched arabinose-galactose side chains attached by the
      rhamnose residues to the backbone. The neutral fraction consisted of a neutral
      arabinogalactan beside minor amounts (about 10%) of a low substituted xyloglucan.
      Further studies on interaction between the 1340 kDa acidic rhamno
      arabinogalactans II and III and mistletoe lectin Viscum album agglutinin I (VAA
      I) revealed binding capacities between these compounds, while the neutral
      polymers interacted significantly less with VAA I. Only partial binding of VAA I
      was observed by incubation of the lectin with polysaccharide II. Similar
      interactions of polysaccharide fraction III with VAA I was measured in a BIACRORE
      biosensore system. Using the hemagglutination test, increased agglutination of
      erythrocytes was observed when mistletoes lectin I and the respective
      polysaccharide fractions were present together in the assay. All these data
      indicate clearly strong interaction between VAA I and Viscum polysaccharides.

PMID- 10965424
TI  - Synthesis and antibacterial activity of new arylamido derivatives of 6 beta
      aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta
      aminodesacetoxycephalosporanic acids.
AB  - New semisynthetic penicillins and cephalosporins have been synthesized by
      acylation of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta
      aminodesacetoxycephalosporanic acids with ortho-substituted aromatic acids, using
      the method of mixed anhydrides. The chemical structures of the compounds obtained
      were confirmed by elemental analysis and by IR- and 1H-NMR spectra. Antibacterial
      activities of the compounds were determined by the macrodilution susceptibility
      test in brain-heart infusion broth. Test organisms producing beta-lactamases:
      Bacillus subtilis L2, Bacillus subtilis HB2, Bacillus cereus 30, Bacillus
      subtilis 6633 ATCC, Bacillus mycoides 924; Staphylococcus aureus 1/45 "Oxford" as
      Gram-positive bacteria, and Escherichia coli 111, Escherichia coli K12/F-?lac-/,
      Escherichia coli K12/F-?lambda-/, Escherichia coli K12/F-?lambda-?lac+/ as Gram
      negative bacteria. In general, the derivatives of 6 beta-aminopenicillanic acid
      were more active than 7 beta-aminocephalosporanic and 7 beta
      aminodesacetoxycephalosporanic acid derivatives. Among all the compounds
      synthesized 6 beta-[4'-(dimethylamino)-azobenzene-2-amido]penicillanic acid and 6
      beta-(N-phenylanthranilamido)penicillanic acid showed the best activity and were
      with the broadest spectrum of action.

PMID- 10965425
TI  - Transfer of aciclovir from plasma to human breast milk.
AB  - Aciclovir (CAS 59277-89-3) is frequently used in herpes simplex virus diseases,
      but administration to lactating women occurs only rarely. Therefore, information
      about the pharmacokinetics of aciclovir in human breast milk is limited. The
      concentration in breast milk is 2 to 3 fold increased compared to plasma. The
      reason for this increase is unknown until now. An active transport mechanism has
      been assumed. The aim of this study was to prove whether the higher concentration
      of aciclovir in human breast milk is due to only a passive transfer. Two chambers
      separated by a semipermeable membrane were used. The first chamber contained
      plasma with aciclovir, the second chamber breast milk without aciclovir. The
      increase in aciclovir concentration in the second chamber was determined. The
      concentration of aciclovir in breast milk exceeded that of plasma after 2 h and
      reached a higher concentration. Thus, the higher aciclovir concentration in human
      breast milk is due to passive diffusion. No active transport mechanism is needed.

PMID- 10965426
TI  - Effect of topically applied dexpanthenol on epidermal barrier function and
      stratum corneum hydration. Results of a human in vivo study.
AB  - In a randomized, double-blind, placebo-controlled study the effect of topical
      dexpanthenol (CAS 81-13-0) formulated in two different lipophilic vehicles on
      epidermal barrier function in vivo was carried out. Seven days' treatment with
      dexpanthenol improved stratum corneum hydration and reduced transepidermal water
      loss. Active treatment was statistically different from the vehicle control on
      both measures. Our results suggest that topical dexpanthenol formulated in either
      lipophilic vehicle stabilizes the skin barrier function.

PMID- 10965427
TI  - In vitro studies of poorly absorbed drugs using porcine intestine in the ring
      model RIMO.
AB  - Two compounds, an aminobisphosphonate (A) and a steroid (B), showing a very large
      difference in lipophilicity (log PC (A) = O, log PC (B) > 8) but both revealing
      very poorly absorption in vivo of less than 1% were tested in respect of in vitro
      absorption and mucoadhesion using a model with porcine intestine named RIMO (ring
      model). Explanations for the poor absorption of the two compounds were
      investigated in order to propose methods for absorption enhancement. Moreover,
      absorption and mucoadhesion were measured for different parts of intestine with
      radiolabelled substances. Last but not least the inhibiting effect of calcium
      ions was investigated as well as enhancement by DTT (dithiothreitol), EDTA and
      bile. Results showed that mucus plays an important role in oral bioavailability.
      The aminobisphosphonate formed a complex with calcium ions which was insoluble in
      the mucus and resulted in a smaller amount of substance being absorbed. The very
      lipophilic steroid was kept back from the mucosa by the hydrophilic mucus, but
      addition of the solubilizer bile increased the absorption. The results were in
      good agreement with in vivo bioavailability data. Therefore, simplicity of the
      model and easy access of porcine intestine by slaughter houses make RIMO a
      valuable tool for investigations concerning the role of mucus and influences of
      diverse additives on absorption.

PMID- 10965428
TI  - A quotient of independent measurements as outcome. A statistical method to
      compare groups in biological experiments.
AB  - The methodology in this paper was proposed to analyze biological data. The
      variable of interest, W, was a quotient of measurements; W: = X/(Y.Z). The
      peculiar problem was that X, Y, and Z could only be determined in three
      independent units of observation which were destroyed in the course of each
      measurement. A test statistic for the comparison of two treatments in W is
      proposed which is based on robust measures of location and dispersion in order to
      account for outliers in the data. Simulations showed that the test statistic
      proposed is approximately normally distributed, even for small sample sizes.

PMID- 10965429
TI  - Methods of contracting for health services: lessons on cost and quality from the
      United States.

PMID- 10965430
TI  - The control of health care spending in short and long terms: notes on the French
      experiment (1996-1998).

PMID- 10965431
TI  - Health financing during an economic crisis: Indonesian experiences (July 1997
      July 1998).

PMID- 10965432
TI  - Managed care: the determinants of cost and quality.

PMID- 10965433
TI  - Cost containment in the Australian Health Care System--an unexpected success.

PMID- 10965434
TI  - [The century-long trends of the French hospital system: an analysis in terms of
      regulation].
AB  - This article is an inquiry about growth of hospitals expenses. The analysis is
      founded on the long term construction of monetary series. These series show
      evidence of three characteristics: growth of hospitals expenses between 1815 and
      1993, development trough a succession of stages, existence of long term cyclic
      fluctuations contrary to the Kondratieff's movements.

PMID- 10965435
TI  - Influence of cadmium and zinc sulphates on the function of human T lymphocytes in
      vitro.
AB  - Substances present in our environment influence the whole organism, including the
      immune system. Metals are one of the principal parts of these substances. It is
      generally supposed that they may have stimulating effect on immunity system in
      low concentrations in comparison with high concentrations in which they are
      toxic, with variations of each metal. There are differences between for example
      cadmium and zinc, and cadmium is toxic in low concentrations either. The effect
      of cadmium on the immune system has not been studied so deeply as the influence
      of zinc. In our work, we are interested in the study of immunomodulation caused
      by cadmium in comparison with the influence of zinc. We tested the effect of
      cadmium and zinc sulphates on human T lymphocytes in vitro. Molar concentrations
      of salts used in our work were from 10(-2) M to 10(-10) M. The influence of
      metals on lymphocytes in cell culture was studied by the expression of surface
      antigen CD69, blast transformation and IL-2 and IL-4 intracellular production
      after 2, 24 and 72 h cultivation. Cells were analyzed by flow cytometry using
      monoclonal antibodies. The results show more expressive differences in blast
      transformation. There are stimulating effects of cadmium in concentrations 10(-3)
      M, 10(-4) M and 10(-8) M, and zinc 10(-3) M. The most suppressive effect is in
      concentrations 10(-10) M of cadmium and 10(-8) M of zinc. The highest CD69
      expression is in concentrations 10(-4) M to 10(-6) M of cadmium, and 10(-3) M of
      zinc. There are minimal differences in intracellular cytokine production in CD4+
      lymphocytes effected by various metal concentrations used and between cadmium and
      zinc salts after 2 hours cultivation. There is the elevation of cytokines
      negative cells after the cultivation lasting 24 hours. Our investigation of
      metals' influence by different methods shows possibilities for further research.

PMID- 10965436
TI  - The state of health of the Romany population in the Czech Republic.
AB  - The health state pilot study of Romany nationality people (432 adults and 105
      children) intended on relationship between social characteristics and
      presentation of health problems, further on the index of absence from work due to
      illness and mutual relations. The frequent occurrence of diagnostic groups E10
      14, F70-79 and M00-99 was found among the group of men. The results of
      investigation are valid in particular for our examined group.

PMID- 10965437
TI  - New serovars of Plesiomonas shigelloides--1992-1998.
AB  - Most of the 26 new O (O77-O102) and 10 new H (H42-H50) and H1a1d antigens were
      found in various P. shigelloides strains isolated from man and other mammals,
      birds, fish, and water and water insects, not only in the Czech Republic but also
      in 12 foreign countries.

PMID- 10965438
TI  - Mortality of the population in Slovakia: past and present.
AB  - This contribution presents an analysis of the health status of the Slovakian
      population using trends in overall mortality, death rates from major diseases,
      and of other health indicators. The health status of the Slovak population at the
      beginning of this century as well as at the time of the establishment of
      Czechoslovakia in 1918 was very bad. This situation is demonstrated by the
      extremely high infant mortality rate, short life expectancy and enormous
      mortality from infectious diseases, particularly from tuberculosis. Despite
      progress before the Second World War, only in the postwar period was the health
      status comparable with other developed countries of western Europe as there was a
      rapid improvement of health lasting until the middle of 1960s. This positive
      evolution resulted mainly from the extensive use of preventive measures against
      infectious diseases, contributing to the decline of infant mortality and the
      gradual prolongation of life expectancy. A simultaneous rapid increase of
      noninfectious, mainly chronic diseases, particularly of cardiovascular diseases
      and cancer was observed. Attempts to deal with this increase lead only to
      enlargement of treatment facilities. The whole health policy in prevention,
      including the pre- and postgradual education of physicians and paramedical
      personnel, remained in its traditional orientation against infectious diseases.
      This situation, together with low social and moral standard of the population,
      increasing consumption of cigarettes, alcohol and inadequate composition and
      superfluous food led to the rapid deterioration of the health status of the
      Slovakian population in the past three decades. The orientation of the health
      policy to the prevention of noninfectious, mainly chronic, degenerative diseases
      and, above all a change of the attitude of the inhabitants of this country to
      their own health, present the only way to the substantial and rapid improvement
      of the health status of the population of Slovakia.

PMID- 10965439
TI  - The immunogenicity and reactogenicity of the trivalent vaccine, Trimovax,
      indicated for prevention of measles, mumps, and rubella, in 12-month-old children
      in Belarus.
AB  - In the Republic of Belarus, immunization of children against measles and mumps
      had been carried out using monovalent preparations according to the national
      schedule of measles vaccination at 12 months of age and mumps vaccination at 24
      months of age. A rise of rubella incidence in the last few years (i.e., for the
      official registration period 1980 to 1998, there was an increase from 72.2 to
      607.5 cases per 100,000 population) made it necessary to implement immunization
      against this infection, as well. Therefore, in 1996, combined vaccination against
      measles, mumps, and rubella of 12-month-old children was carried out for the
      first time in a clinical trial that used the vaccine Trimovax [Aventis Pasteur
      (formerly, Pasteur Merieux Connaught), Lyon, France]. The reactogenicity of the
      vaccine was investigated in 372 children. Post-vaccination reactions were noted
      in 5.6% of children; in 1.3% of children the reactions were classified as severe
      [i.e. associated with body (axillary) temperature > or = 38.6 degrees C]. For the
      evaluation of immunogenicity, sera from 324 children were obtained 2 to 2.5
      months after inoculation, and serum antibody levels were measured by enzyme
      immunoassays. Among the vaccines, protective antibody titers (expressed in
      inverse of dilution units) were observed to measles (> or = 1:50) in 97.8%, to
      mumps (> or = 1:50) in 93.8%, and to rubella (> or = 1:100) in 96.0% of children.
      Antibodies to all three components of the vaccine were mainly present in
      intermediate (1:200-1:800) or high (> or = 1:1600) titers: to measles in 96.3%;
      to mumps in 75.8%; and to rubella in 73.5% of vaccines. The results of these
      trials are evidence of the good safety and immunogenicity of this MMR vaccine,
      which provides an alternative to the currently used measles and mumps
      monovaccines, with the additional benefit of providing immunity against rubella,
      as well.

PMID- 10965440
TI  - Influence of some antibiotics on lipase and hydrophobicity of Acinetobacter
      baumannii.
AB  - Effect of four antibiotics (cefotaxime, ceftazidime, cefepime and ofloxacin) at
      subinhibitory concentrations (sub-MICs) (1/4, 1/8 or 1/16 of the MICs) on lipase
      and cell surface hydrophobicity of a clinical isolate of Acinetobacter baumannii
      16265 was studied. Lipase activity in the majority of the cases was not
      significantly changed. Small alterations were drug and concentration dependent.
      The most efficient ceftazidime at 1/4 of the MIC reduced lipolytic activity to
      78.7% of the control value. On the other hand, all beta-lactam antibiotics mainly
      at the highest concentration (1/4 of the MICs) most effectively decreased surface
      hydrophobicity of the studied strain. Hydrophobicity of treated bacteria
      evaluated by their adherence to xylene was in the range of 11.2 to 29.9% of the
      control values. The most efficient was cefepime. Whether the modifications in
      potential virulence factors of the bacteria tested observed in in-vitro
      experiments would have the clinical importance, remains to be evaluated.

PMID- 10965441
TI  - The assessment of risk to acquired hypothyroidism from exposure to PCBs: a study
      among Akwesasne Mohawk women.
AB  - PCBs are a family of 209 chemical compounds, each of which consists of two
      benzene rings and 1 to 10 chlorine atoms. Their long-term stability and
      dispersion into the environment and the food chain have caused concern about
      their impact on humans and the environment. Native American communities are
      believed to be at particularly high risk of such exposure since they typically
      are more dependent than other populations on local fish and game as a food
      source. We have evidence for a significant excess in incidence and prevalence of
      hypothyroidism among Mohawks, particularly older women, as compared to other
      populations. The goal of the current project is to compare serum PCB
      concentrations to indicators of thyroid function in controls and patients with
      demonstrated thyroid dysfunction. Studies on experimental animals (rats) have
      shown significant depression of circulating levels of T4 and moderate reductions
      in levels of T3 after exposure to PCBs. We are conducting a retrospective
      observational case-control study. The participants are Mohawk women 30 years of
      age and older. Controls are participants in an ongoing environmental epidemiology
      study, whose thyroid hormone tests show a normal function. Our study aims to
      investigate the association between long-term exposure to PCBs and acquired
      hypothyroidism, to identify the critical exposure routes and to develop and apply
      toxic equivalents for thyroid disease for the various PCB congeners. PCB exposure
      is assessed by ultra-trace, congener-specific determination in blood specimen
      using GC/ECD. The study is currently ongoing. We have analyzed 46 samples of
      cases and 75 samples of controls.

PMID- 10965442
TI  - Participation of Chlamydia pneumoniae in an epidemic of respiratory infections in
      Slovakia.
AB  - In human sera collected in three regions of Slovakia during an epidemic of
      respiratory infections, both genus-specific chlamydial and species-specific anti
      Chlamydia pneumoniae antibodies, as detected by enzyme-linked immunosorbent assay
      and microimmunofluorescence test, respectively, were found. Based on
      seroconversion or significant rise of antibody titers and detection of antibodies
      of IgM class, an acute C. pneumoniae infection was indicated in 21 of 298 (7.0%)
      patients tested. The results obtained bring the first evidence on the role of C.
      pneumoniae as respiratory pathogen in Slovakia.

PMID- 10965443
TI  - HIV infection and sexual behaviour among homosexual and bisexual men in
      Bratislava.
AB  - OBJECTIVE: To determine sexual behaviour and HIV prevalence in a sample of
      homosexual and bisexual men in Bratislava. PATIENTS AND METHODS: Participants
      were recruited at gay discotheque in Bratislava in February and June 1996. Saliva
      samples were collected for testing the presence of anti-HIV antibodies and a
      questionnaire regarding sexual practice was completed. RESULTS: In the study 170
      men (1st discotheque) and 124 men (2nd discotheque) were enrolled. The prevalence
      of antibodies against HIV was 5.4% and 1.6%, respectively. A group of 119
      attenders (mean age: 25 years) was voluntarily questioned about their sexual
      lifestyle and related behaviour. Sexual orientation of participants was
      following: 66.4% homosexuals, 20.2% bisexuals, 13.4% others. Most responders were
      single and did not ever been married (86.55% vs. 12.6%, respectively). The
      figures of sexual intercourse were: steady partners: 45.38%, non-steady partners:
      49.58%. More individuals were using condoms (70.58% vs. 15.97%, respectively),
      while only 28.57% were using them by each chance sexual intercourse. 6.7%
      responders suffered from an other STD and 3.36% were intravenous drug users.
      CONCLUSION: The HIV prevalence (5.4% and 1.6%) was relatively low. Considering
      the high prevalence of unsafe sexual practice further spread of HIV infection
      among homosexual men in Slovakia is to be expected.

PMID- 10965444
TI  - Potential foci of Lyme borreliosis in towns.
AB  - In 1997 the presence of ticks Ixodes ricinus infected with the agent of Lyme
      borreliosis was detected on the vegetation of Kosice urban agglomeration. The
      density of ticks on the vegetation of pericentral area islands of forest stands
      and neglected gardens was 2.4 times lower than that observed in a peripheral park
      forest. Only sporadical findings of ticks were reported from the industrial
      central part of town with remnants of uncultivated vegetation. Central parks and
      housing estates were actually tick-free. Borrelia-infected ticks, from 12.8 to
      15% were found in the park forest and pericentral areas. The results indicate
      potential risks for humans and domestic animals coming in contact with borrelia
      infected ticks, also in the territory of large towns.

PMID- 10965446
TI  - Effect of recirculation air cleaners on indoor air quality in a children's home.
AB  - The subject of this study was to assess the efficacy of the air cleaners provided
      by the Czech Power Company CEZ, J.S.C., and the foundation Social and Therapeutic
      Help Fund, Prague, to selected children's homes within the framework of the
      project "Clean air for flooded Moravia". The study was conducted in a children's
      home in Ostrava-Hrabova. It was concluded that the air cleaners represent an
      effective mean for improving indoor air quality.

PMID- 10965445
TI  - Comparative analysis of results from studies of goitre in children from Bulgarian
      villages with nitrate pollution of drinking water in 1995 and 1998.
AB  - The role of nitrates in goitre genesis has been discussed for a long time. In the
      present report a comparative analysis is made of results obtained in villages
      with nitrate pollution of the drinking water. In two pairs of villages children
      aged between 3 and 14 were included, whose thyroid status was investigated by a
      clinical examination. The study was carried out in 2 stages--in 1995 and 1998. In
      this period the goitre incidence was significantly reduced in both sexes. Both
      investigations showed a higher relative risk of goitre in children exposed to
      water pollution by nitrates. In the first, as well as in the second examination,
      goitre was diffuse. We concluded that nitrate pollution of drinking water
      undoubtedly participated in goitre genesis. We did not underestimate the
      strumigenic effect of nitrates in the diet as they were not the object of our
      investigation and which, according to WHO experts, have a less strumigenic
      effect. After the first investigation we recommended a higher antistrumin dose as
      prophylaxis. That is why we conclude that the considerable goitre reduction in
      the second investigation was the positive result of the doubled antistrumin
      prophylaxis during the period between the two investigations.

PMID- 10965447
TI  - Dietary guidelines in the Czech Republic. I.: Theoretical background and
      development.
AB  - Setting dietary guidelines for the healthy population of the Czech Republic has
      respected the methodical steps suggested by authors as follows: consideration of
      dietary guidelines was preceded by the consensus on general goals and methods,
      e.g. health and well-being promotion at the population level. The guidelines
      cover a total diet, not only a part of it and have to be realistic, with respect
      to actual frequency of food in majority of population. The second step was the
      declaration of nutritional goals with respect to achieving the RDI. The third
      step was dividing the food into defined food groups according to the following
      criteria: the food contained in one food group had the same/similar nutritional
      characteristics with regard to achieving the adequate of decreased intake. Within
      the groups several sub-groups were set, associating foods with another specific
      nutrient content. The fourth step was the setting the serving sizes as an
      equivalent for each food group. These equivalents must reflect typical average
      consumed amount of food and always within the group the content of the main
      nutrient has to be same/similar. The fifth step was setting nutritional profile
      of each group and/or sub-group. This profile represented the content of energy,
      proteins, lipids, carbohydrates, vitamins and minerals. The sixth step was
      deciding the daily number of servings of each food group, which must allow the
      flexibility as much as possible--authors recommend the interval solution. The
      seventh step was decision about the form (textual and graphic), which presents
      the guidelines. The decision was preceded by the study focused on accepting
      suggested possibilities. The last, eighth step was working out the strategy of
      implementation in practise, which means the summarizing organizational,
      administrative and political arrangements with the aim to be positively accepted
      by the population who identify itself with the principles of the dietary
      guidelines. In the formulation of dietary guidelines in the Czech Republic, the
      authors accepted methods described above and each of the eight steps was
      supported by adequately focused population study.

PMID- 10965448
TI  - [Clinical evaluation of estramustine phosphate and vinblastine in patients with
      hormone-refractory prostate cancer].
AB  - We evaluated the efficacy of the combination of estramustine phosphate and
      vinblastine in 13 patients with hormone-refractory prostate cancer. Of 12
      patients with an elevated prostate specific antigen (PSA) level at the start of
      treatment, 5 (42%) had a greater than 50% decrease in PSA level. In a patient
      with cervical and mediastinal lymph node metastases, about a 57% decrease was
      observed in bidimensional measurement. Side effects were mild and manageable. The
      survival rate was not significantly different between patients who showed a
      greater than 50% decrease in PSA levels or regression of lymph node metastases
      versus the other patients.

PMID- 10965450
TI  - [Retroperitoneal cystadenoma containing elevated concentrations of CA125 and CA19
      9 in the cyst fluid: a case report].
AB  - A 67-year-old female presented with left abdominal distension. A huge
      retroperitoneal cystic mass, measuring over 20 cm in diameter, was found below
      the left kidney. The cyst was punctured percutaneously, and serous fluid was
      aspirated. It was noted that the concentrations of CA125 and CA19-9 in the fluid
      of the cyst were extremely elevated while those in the serum were normal. The
      cyst was resected easily without any adhesion. Microscopically, the cyst was
      lined with a mixture of ciliated and cuboidal serous cells and columnal mucinous
      cells. Immunohistochemical staining of the cyst wall proved positive for CA125 on
      serous cells, and for CA19-9 on mucinous cells.

PMID- 10965449
TI  - [A case of metachronous, multifocal development of liposarcoma in the back of
      left thigh, the left subclavicular region and the right perirenal tissue].
AB  - A 46-year-old woman had received surgery to remove a mass arising from the back
      of the left thigh 13 years before and on the left subclavicular region 3 years
      before. Histological diagnosis of both masses was myxoid type liposarcoma. She
      was admitted to our hospital because of right abdominal pain. Abdominal computed
      tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a
      large retroperitoneal tumor. The removed specimen weighed 1,450 g and measured 24
      x 13 x 9 cm in size. Histological diagnosis was myxoid type liposarcoma. She has
      been free of any recurrence for 4 months postoperatively without adjuvant
      therapy.

PMID- 10965451
TI  - [Penile metastasis from renal cell carcinoma: a case report].
AB  - Penile metastasis is rare. It occurs in the advanced stage of genitourinary
      cancer, with many other metastases in various organs. All 7 patients with penile
      metastasis of renal cell cancer, reported in the Japanese literature, died within
      a year. Our case was not the exception. A 69-year-old male presented with right
      flank pain and penile induration. Right renal cancer with liver invasion and
      multiple pulmonary metastases were found. Microscopic examination revealed a
      sarcomatous pattern. He died 4 months later.

PMID- 10965452
TI  - [A case of urinary stone in ureterocele extracted transurethrally after ESWL].
AB  - A 66-year-old man was referred to our hospital with chief complaints of
      difficulty in urination and terminal micturition pain. Ureteroceles were
      identified bilaterally, and a ureteral stone (19 x 12 mm) existed in the right
      ureterocele. After crushing the stone by extra corporeal shock wave lithotripsy
      (ESWL), we removed the stone transurethrally with a small incision in the right
      ureterocele. The vesicoureteral reflux (VUR) was not detected postoperatively.
      Now, we recommend the combination of ESWL and a small transurethral incision of
      the urelerocele for the treatment of ureteral stones in a ureterocele in order to
      prevent postoperative VUR.

PMID- 10965453
TI  - [A case of metachronous adenocarcinoma of the urinary bladder and the right upper
      urinary tract].
AB  - Bilateral hydronephrosis identified by a local physician brought a 65-year-old
      man to our hospital. Emergency percutaneous nephrostomy was bilaterally
      established for obstructive renal failure. After recovering renal function, the
      patient underwent radical cystectomy under the diagnosis of invasive bladder
      cancer and the construction of an ileal conduit. The pathology reported well
      differentiated adenocarcinoma (pT2, pL1, pV1). Five years after the surgery,
      gross hematuria developed. A computed tomographic scan revealed right
      hydronephrosis with a solid mass in the upper calyx. The urinary cytology was
      negative. The patient underwent right nephrectomy in May, 1999. The pathology
      then revealed well differentiated adenocarcinoma in the renal pelvis and ureter
      (pT3, pL0, pV0 and pT1, pL0, pV0, respectively). He is alive with mild chronic
      renal insufficiency with evidence of tumor at ten months after surgery. To our
      knowledge, this is the first case of metachronous adenocarcinoma of the urinary
      bladder and the upper urinary tract reported in the Japanese literature.

PMID- 10965454
TI  - [Small cell carcinoma of the urinary bladder: a case report].
AB  - We report a case of small cell carcinoma of the urinary bladder. The patient was
      a 58-year-old man complaining of gross hematuria. Clinical examination revealed a
      non-papillary, broad-based tumor on the right bladder wall with a clinical stage
      of T3a, N0, M0. Neoadjuvant intraarterial infusion chemotherapy with
      methotrexate, adriamycin and cisplatin was performed, but it was ineffective.
      Three weeks later we performed a radical cystectomy. The operative specimen of
      the tumor revealed small cell carcinoma. It was staged pT3aN0M0R0L2V1.
      Postoperatively, 1 course of adjuvant chemotherapy using cisplatin and etoposide
      was performed. The patient is alive without any evidence of tumor recurrence at 6
      months after operation.

PMID- 10965455
TI  - [Small cell carcinoma of the urinary bladder: a case report].
AB  - A 64-year-old man presented with asymptomatic gross hematuria. Cystoscopy
      revealed a non-papillary broad-based tumor on the posterior wall of the bladder.
      He had no evidence of metastases. Urine cytology showed a cluster of molded tumor
      cells with naked hyperchromatic nuclei, which indicated small cell carcinoma. He
      received preoperative irradiation to the bladder and underwent partial
      cystectomy. Pathological examination of the specimen showed small cell carcinoma
      at the stage of pT2. Two years after the operation, he had no evidence of
      recurrence.

PMID- 10965456
TI  - [A case of bladder hemangioma showing bladder tamponade during late pregnancy].
AB  - We report a case of bladder hemangioma manifesting bladder tamponade during
      pregnancy. A 25-year-old woman at 36 weeks of gestation was admitted with a two
      week history of gross hematuria and clot retention. Blood hemoglobin
      concentration was 6.3 g/dl. After blood transfusion and Caesarian section,
      cystoscopy was performed. Bleeding was noticed from a strawberry-like tumor 5 mm
      in diameter near the right ureteral orifice, which was easily resected
      endoscopically. Histopathological diagnosis was cavernous hemangioma of the
      urinary bladder. This is the first report of a case of bladder hemangioma during
      pregnancy.

PMID- 10965457
TI  - [A case of emphysematous cystitis].
AB  - Emphysematous cystitis is a rare lower urinary tract infection. Patients with
      diabetes mellitus, neurogenic bladder, and recurrent urinary tract infection are
      generally at higher risk of this disease. A 71-year-old woman with neurogenic
      bladder was referred from the internal medicine department because of urinary
      retention. Abdominal radiography and computed tomographic (CT) scanning revealed
      a characteristic accumulation of air in the wall and lumen of the urinary
      bladder. Emphysematous cystitis was improved by antibiotic therapy and urinary
      drainage. CT scan was a sensitive method for detecting early signs and confirming
      the diagnosis.

PMID- 10965458
TI  - [A case of paravesical foreign body granuloma due to surgical sponge retained for
      40 years].
AB  - A 67-year-old man complained of vague pain in the lower abdomen persisting over
      10 years. A hard mass was palpable just under an operative scar (right Gibson
      incision for ureterolithotomy performed 40 years previously). In addition to the
      patient's history and physical examination, abdominal echography, computerized
      tomography and nuclear magnetic resonance imaging (MRI) were performed and
      resulted in a preoperative diagnosis of retroperitoneal gauzeoma. The paravesical
      mass, 7 x 6 x 6 cm in size, was surgically removed, which was an encapsulated
      granuloma surrounding a surgical sponge. The possibility of foreign body
      granulomas due to a retained surgical sponge (so-called gauzeomas) should be
      considered in patients who have a previous history of abdominal operations.

PMID- 10965459
TI  - [Primary transitional cell carcinoma of prostate: a case report].
AB  - A 67-year-old male was admitted with a three-month history of voiding difficulty.
      Prostate specific antigen remained within the normal limit. Under the diagnosis
      of benign prostatic hypertrophy, transurethral resection of prostate was
      performed. Pathological examination of the resected specimens of the prostate
      revealed transitional cell carcinoma. Two courses of systemic M-VAC
      (methotrexate, vinblastine, doxorubicin, cisplatin) chemotherapy were performed,
      followed by cystoprostatourethrectomy, pelvic lymphadenectomy, and ileal conduit
      construction. Now one year has elapsed, with no clinical signs of recurrence.

PMID- 10965460
TI  - Adenocarcinoma of the prostate with ectopic antidiuretic hormone production: a
      case report.
AB  - An 88-year-old patient with a poorly differentiated adenocarcinoma of the
      prostate gland was found to have all cardinal findings of syndrome of
      inappropriate antidiuretic hormone secretion (SIADH). Elevated levels of
      antidiuretic hormone were found in the patient's serum and in the prostatic tumor
      and the cytoplasms of the tumor was positive for prostate specific antigen and
      was faintly positive for antidiuretic hormone (ADH). He responded well to
      combination therapy of androgen blockade with leuprorelin acetate and flutamide,
      and laboratory findings of SIADH and serum ADH level returned to normal. However,
      he died of sudden profuse bleeding caused by gastric ulcers 6 months after the
      therapy. Ten cases of SIADH caused by prostatic cancer have been reported
      including the present case.

PMID- 10965461
TI  - [A case of synchronous cervical lymph node metastases from testicular and thyroid
      cancers showing mixed response to chemotherapy].
AB  - We report a case of synchronous presentation of thyroid cancer and testicular
      seminoma with lymph node metastasis. A 37-year-old man presented with right
      scrotal swelling and multiple lymph node swelling. We performed right radical
      orchiectomy, and histological examination revealed a seminoma of the testis.
      After systemic work-up for staging, we diagnosed the patient with multiple lymph
      node metastasis of the seminoma, and administered three cycles of bleomycin,
      etoposide, and cisplatin (BEP) therapy. Although the chemotherapy was very
      effective for the retroperitoneal and left cervical lymph node metastases, the
      right cervical tumor did not change. Retroperitoneal lymphadenectomy combined
      with right cervical lymph node dissection and hemi-thyroidectomy were performed
      on September 8, 1998. Pathological examination of the thyroid revealed papillary
      thyroid cancer and its right cervical lymph node metastasis. There was no
      evidence of viable cancer cells from either of the primary cancers in the
      retroperitoneal lymph node. Unresponsiveness to chemotherapy for metastatic
      lesions from testicular cancer might be a useful clue to detect primary tumors of
      other origins.

PMID- 10965462
TI  - [A case of Kallmann syndrome: diagnostic usefulness of cranial magnetic resonance
      imaging].
AB  - We report a case of Kallmann syndrome in which the cranial magnetic resonance
      imaging (MRI) findings of the olfactory tract were useful in making the
      diagnosis. A 20-year-old male who complained of delayed puberty was referred to
      our hospital in November 1998. He presented with hypogonadism and anosmia. The
      plasma levels of testosterone, luteinizing hormone (LH) and follicle stimulating
      hormone (FSH) were low. Pituitary and Leydig cell functions were normal by the LH
      releasing hormone test and human chorionic gonadotropin (hCG) loading test,
      respectively. The karyotype was normal (46, XY). The smell test showed anosmia.
      After administration of hCG, a good response of plasma testosterone level and
      masculinization were recognized. Cranial MRI findings revealed an absence of
      olfactory bulbs and hypoplastic olfactory sulci. These MRI findings are
      characteristic of Kallmann syndrome and allowed us to confirm our diagnosis, in
      addition to classically used endocrinological and olfactory examination.

PMID- 10965463
TI  - [Clinical statistics on patients and operations during a 20-year period (1978
      1997) at Department of Urology, Jikei University School of Medicine].
AB  - A statistical analysis was made of diseases, patients, and operations at our
      department in the four affiliated hospitals of Jikei University School of
      Medicine from 1978 through 1997. Our findings were as follows. Newly diagnosed
      urogenital malignancies, except testicular tumors, have been increasing in the
      last two decades among both outpatients and inpatients. Urogenital infections,
      including tuberculosis, have gradually been decreasing in the last two decades.
      The treatment of urinary stone diseases was markedly altered by the induction of
      extracorponeal shock wave lithotripsy.

PMID- 10965465
TI  - Cell biology of aluminum toxicity and tolerance in higher plants.
AB  - Aluminum is the major element in the soil and exists as a stable complex with
      oxygen and silicate in neutral and weakly acidic soil. When the soil pH is lower
      than 4.5-5.0, Al is solubilized in the soil water and absorbed by plant roots.
      Absorbed Al inhibits root elongation severely, and the elongation of roots
      exposed to Al3+ as low as mumol level is inhibited within an hour(s). Thus much
      research has been conducted to understand the mechanism of Al toxicity and
      tolerance. Al is located specifically at the root apex. Al-sensitive plants
      absorb more Al than do Al-tolerant plants, and thus the exclusion mechanism of Al
      is the major idea for Al tolerance. The understanding of Al stress in plants is
      important for stable food production in future. Al is a complicated ion in its
      chemical form and biological function. In this chapter, mechanisms of Al toxicity
      and tolerance proposed during the past few decades as well as future topics are
      described from physiological and molecular points of view.

PMID- 10965464
TI  - [Clinical statistics on in-patients and operations during a 14-year period (1986
      1999) at Department of Urology, Gunma Cancer Center].
AB  - The patients, diseases and operations experienced between 1986 and 1999 in our
      department were analyzed. The number of in-patients has been increasing since
      1995. Renal cell carcinoma, urinary bladder cancer and testicular cancer have
      been gradually increasing recently, and in-patients with prostate cancer have
      increased markedly. Pelvic and ureteral cancers were almost constant during this
      period. Radical nephrectomy and prostatectomy have been increasing since 1994 and
      1990, respectively. The examinations for malignancy, especially prostate biopsy,
      have been increasing.

PMID- 10965466
TI  - Gonadal development in mammals at the cellular and molecular levels.
AB  - In mammals, although sex is determined chromosomally, gonads in both sexes begin
      development as similar structures. Until recently it was widely held that female
      development constituted a "default" pathway of development, which would occur in
      the absence of a testis-determining gene. This master gene on the Y chromosome,
      SRY in the human and Sry in the mouse, is thought to act in a cell-autonomous
      fashion to determine that cells in the gonadal somatic population develop as pre
      Sertoli cells. Triggering of somatic cell differentiation along the Sertoli cell
      pathway is therefore a key event; it was thought that further steps in gonadal
      differentiation would follow in a developmental cascade. In the absence of
      Sertoli cells, the lack of anti-Mullerian hormone would allow development of the
      female Mullerian duct and absence of Leydig cells would prevent maintenance of
      the Wolffian duct. Recent findings that female signals not only maintain the
      Mullerian duct and repress the Wolffian duct but also suppress the development of
      Leydig cells and maintain meiotic germ cells, together with the finding that an X
      linked gene is required for ovarian development and must be silenced in the male,
      have shown that the female default pathway model is an oversimplification.
      Morphological steps in gonadal differentiation can be correlated with emerging
      evidence of molecular mechanisms; growth factors, cell adhesion, and signaling
      molecules interact together, often acting within short time windows via
      reciprocal control relationships.

PMID- 10965467
TI  - The Chlorella hexose/H(+)-symporters.
AB  - The physiology, molecular biology, and biochemistry of the inducible hexose
      uptake protein of Chlorella kessleri is reviewed. The protein encoded by the HUP1
      gene is the most intensively studied membrane transporter of plants. Responsible
      for substrate accumulation up to 1500-fold, it translocates one proton together
      with one hexose, and the cell invests 1 ATP per sugar transported. Kinetics
      suggest that substrate accumulation is mainly brought about by a large delta Km
      (Kminside >> Kmoutside). The HUP1 protein (534aa) consists of 12 transmembrane
      helices of which at least helices I, V, VII, and XI interact with the sugar
      during translocation and participate in lining the transport path through the
      membrane. The helix packing might very well be identical to the one suggested for
      the E. coli lac permease, although the mechanism for transport and proton
      coupling that has been suggested for lac permease (Kaback, 1997) certainly does
      not hold for the Chlorella symporter; both are distantly related members,
      however, of the MFS-family of transporters. HUP1 has been functionally expressed
      in Schizosaccharomyces pombe, Saccharomyces cerevisiae, Escherichia coli, Volvox
      carteri, and in Xenopus oocytes.

PMID- 10965468
TI  - Mechanisms of early neural crest development: from cell specification to
      migration.
AB  - The neural crest is a group of embryonic progenitors that forms during the
      process of neurulation by interactions that take place between the prospective
      epidermis and the specified neuroectoderm. Although initially an integral part of
      the neuroepithelium, neural crest cells separate from the central nervous system
      primordium by a process of epitheliomesenchymal transition and become a motile
      cell population. These mesenchymal cells then migrate through stereotypic
      pathways, some of which are common and others unique to various vertebrate
      species. Furthermore, the availability of distinct migratory pathways also
      differs according to embryonic stage and axial level. Studies have begun to
      address the molecular basis of neural crest specification, delamination, and
      migration. The present review summarizes some major advances in our understanding
      of the nature of the intercellular interactions and the molecules that mediate
      them during early phases of neural crest ontogeny.

PMID- 10965469
TI  - Regulation and expression of metazoan unconventional myosins.
AB  - Unconventional myosins are molecular motors that convert adenosine triphosphate
      (ATP) hydrolysis into movement along actin filaments. On the basis of primary
      structure analysis, these myosins are represented by at least 15 distinct classes
      (classes 1 and 3-16), each of which is presumed to play a specific cellular role.
      However, in contrast to the conventional myosins-2, which drive muscle
      contraction and cytokinesis and have been studied intensively for many years in
      both uni- and multicellular organisms, unconventional myosins have only been
      subject to analysis in metazoan systems for a short time. Here we critically
      review what is known about unconventional myosin regulation, function, and
      expression. Several points emerge from this analysis. First, in spite of the high
      relative conservation of motor domains among the myosin classes, significant
      differences are found in biochemical and enzymatic properties of these motor
      domains. Second, the idea that characteristic distributions of unconventional
      myosins are solely dependent on the myosin tail domain is almost certainly an
      oversimplification. Third, the notion that most unconventional myosins function
      as transport motors for membranous organelles is challenged by recent data.
      Finally, we present a scheme that clarifies relationships between various modes
      of myosin regulation.

PMID- 10965470
TI  - Plausibility of periodontal disease estimates from NHANES III.
AB  - OBJECTIVES: This study investigated possible reasons for observed discrepancies
      in prevalence estimates and measures of association for periodontal disease
      between phases (1988-91 and 1991-94) of the third National Health and Nutrition
      Examination Survey (NHANES III). METHODS: NHANES III data on CD-ROM were obtained
      from the National Center for Health Statistics. Accompanying documentation states
      that each phase and combined phases constitute national probability samples of
      the US population. Weighted estimates of prevalence (percent of persons affected)
      and extent (percent of sites affected) for previously reported thresholds of
      gingival bleeding (GB), attachment loss (AL), and probing pocket depth (PD) were
      generated using data from all 15,511 persons aged 13-90 years who received
      periodontal examinations. Odds ratios for associations between four selected risk
      indicators and both PD and AL were compared between phases. RESULTS: Phase 2
      estimates of GB and PD were as much as 56 percent lower than phase 1 estimates
      and both were different from combined-phase estimates. However, AL prevalence was
      consistent between phases. Prevalence differences between phases could be
      explained in part by examiner variations. Odds ratios for PD differed between
      phases by as much as one-third, although the direction and precision of
      associations were not affected, and differences were reduced after controlling
      for examiner. CONCLUSIONS: Combined-phase estimates of GB and PD prevalence and
      extent differ from previously published estimates derived from Phase 1,
      apparently because estimates in at least one phase of the NHANES III study are
      biased. However, associations with selected risk indicators were fairly
      consistent between phases.

PMID- 10965471
TI  - Periodontal disease estimates in NHANES III: clinical measurement and complex
      sample design issues.
AB  - OBJECTIVE: This paper evaluates the possibility that examiner bias or other
      factors contributed to an observed decline in pocket depth and gingivitis between
      the two three-year sequential periods of time (or phases) covered by the Third
      National Health and Nutrition Examination Survey (NHANES III). METHODS:
      Prevalences of periodontal conditions were analyzed using data from two sets of
      repeat oral health examinations by examining dentists of NHANES III sample
      persons. The first set includes sample persons who were examined twice by the
      same examining dentist at an interval of one to six weeks. The second set
      includes sample persons who were assessed on the same day by both an examining
      dentist and a reference dentist. Other possible sources of error also were
      evaluated. RESULTS: Overall kappa statistics measuring agreement between or
      within dental examiners were within the range observed for other periodontal
      disease surveys. While differences were found among dentists in the prevalence of
      pocket depth of 4 mm or more, for each group of sample persons assessed by a
      reference examiner-examining dentist pair, the reference examiner's periodontal
      measurements closely corresponded to measurements made by the examining dentists.
      CONCLUSIONS: Differences between dental examiners in prevalences of periodontal
      conditions may be due in part to the fact that examinees were not randomly
      assigned to examiners. As a result, the sample persons examined by each dentist
      may not have been alike in characteristics thought to affect periodontal disease
      status. These findings suggest that the observed declines in periodontal health
      status between phases is not due to examiner bias. This unexplained decline may
      be the result of sampling variation. It is recommended that combined six-year
      survey results be presented whenever possible.

PMID- 10965472
TI  - President's welcome and address dental public health: our journey into the 21st
      century.

PMID- 10965474
TI  - 1998 Public Service Award: Senator Edward M. Kennedy.

PMID- 10965475
TI  - 1998 Special Merit Award: Marsha Cunningham, RDH, MS.

PMID- 10965473
TI  - President's Award: Dr. Jane Weintraub, DDS, MPH.

PMID- 10965477
TI  - 1998 Distinguished Service Award: Naham C. Cons, DDS, MPH.

PMID- 10965476
TI  - 1998 International Special Merit Award for Outstanding Achievement in Community
      Dentistry: Johng-bai Kim, DDS, PhD.

PMID- 10965478
TI  - 1998 Distinguished Service Award: John K. Peterson, DDS, MPH.

PMID- 10965479
TI  - The John W. Knutson Distinguished Service Award in Dental Public Health--1998
      recipient Myron Allukian, Jr.

PMID- 10965481
TI  - [Trends in the number of human immunodeficiency virus infected persons and AIDS
      cases in Spain: 1980-1998].
AB  - BACKGROUND: To describe the trend in the number of HIV-infected persons and the
      number of AIDS cases in Spain between 1980 and 1998. SUBJECTS AND METHODS: The
      following information was used: annual incidence of AIDS taken from the National
      Registry, AIDS deaths taken from the same registry and from the Registry of Vital
      Statistics, HIV seroprevalence in studies in sentinel populations, HIV incidence
      in cohorts of exposed persons, and reports of HIV infections in the registries
      existing in the autonomous communities. We considered three events of interest-
      HIV infection, AIDS and death--which were related using back-projection and
      compartmental models. RESULTS: HIV spread rapidly in Spain during the years 1980.
      Transmission subsequently declined by more than 50% to figures that probably do
      not exceed 6,000 new infections in 1998. The incidence of AIDS increased to more
      than 7,000 new cases in 1994 and has since declined to some 4,000 cases in 1998.
      The level of AIDS mortality has always been lower than the incidence; it
      increased up to 1995 and then dropped to less than half in subsequent years. The
      number of living persons infected with HIV, including AIDS cases, arose until the
      early years 1990 and has since remained steady at about 125,000 persons. The
      number of cases of living persons with AIDS has increased continuously, and is
      estimated at about 19,000 through the end of 1998. CONCLUSIONS: The recent trend
      in new infections, AIDS cases and deaths is favourable, while the number of
      infected living persons remains very high.

PMID- 10965480
TI  - [Human papillomavirus and human immunodeficiency virus infections as risk factors
      for cervix cancer in women prisoners].
AB  - BACKGROUND: The identification of high risk groups for genital human
      papillomavirus (HPV) infection may contribute to cervical cancer prevention. The
      study was designed to estimate the prevalence of HPV infection and the related
      risk of cervical cancer among imprisoned women. PATIENTS AND METHODS: 157 women
      were visited at the Medical Office of a prison in Barcelona, Spain. Women
      underwent a structured interview, determination of HIV serostatus and detection
      of HPV cervical infection by means of PCR. RESULTS: The prevalence of HPV
      infection was 46%. Prostitution was reported by 38.2% and intravenous drug use by
      64.3%. HIV infection was detected in 56.1%. Cervical cytology revealed 19 women
      with ASCUS and 28 with squamous intraepithelial lesions (SIL) (all grades). HPV
      infection was associated with an increased risk of intravenous drug use for more
      than 10 years (prevalence odds ratio [POR] = 2.9) and seropositivity to HIV (POR
      = 4.7). The increase in risk for SIL related to HIV was explained by the presence
      of HPV. HIV positive women with low CD4 counts may increase the risk for SIL
      independently of HPV. CONCLUSION: HIV positive women are at high risk for HPV
      infection and as a consequence, for developing SIL. HIV positive women should be
      closely monitored for cervical cancer.

PMID- 10965482
TI  - [Decreased activity of 11-beta-hydroxysteroid dehydrogenase in patients with
      Cushing's syndrome].
AB  - BACKGROUND: To study 11 beta-hydroxysteroid dehydrogenase activity in Cushing's
      syndrome. PATIENTS AND METHOD: Measurements of free cortisol, cortisone,
      tetrahydrocortisol and tetrahydrocortisone in 24 h urine samples of patients with
      Cushing's syndrome and controls. RESULTS: The cortisol to cortisone and
      tetrahydrocortisol to tetrahydrocortisone relationship was significant (in
      controls, r = 0.70; p < 0.0001, and r = 0.75; p < 0.0001) respectively, but it
      was not in patients with Cushing's syndrome. CONCLUSIONS: 11 beta-hydroxysteroid
      dehydrogenase activity is decreased in patients with Cushing's syndrome.

PMID- 10965483
TI  - [Cancer and human immunodeficiency virus in the era of combination therapy].

PMID- 10965484
TI  - [The 21st century "AIDS"].

PMID- 10965485
TI  - [Lymphangioleiomyomatosis: study of 15 patients].
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is an uncommon disease of not well
      known evolution. We describe the clinical features and follow-up of a group of
      patients diagnosed of LAM in a hospital pulmonary transplantation programme.
      PATIENTS AND METHODS: 15 women (mean age: 43, range: 36-52) diagnosed of LAM, 9
      at the Hospital Vall d'Hebron and 6 referred from other hospitals, for
      preoperative evolution of lung transplantation, were retrospectively studied.
      RESULTS: Dyspnea appeared in all cases and it was the main symptom. Pleural
      problems in the early evolution of the disease were also very frequent (12 out of
      15 patients). For this reason, pleurodesis was performed in 7 patients and
      pleurectomy in 2 (one of them bilateral). Thoracic CT scan showed very
      characteristic cystic images and abdominal CT proved the presence of
      extrathoracic associated angiomyolipomas in one case. In two patients, LAM was
      diagnosed after studying the explanted lung. These two patients had been
      previously misdiagnosed of emphysema and pulmonary haemosiderosis. Survival since
      the beginning of symptoms was 82 and 49%, 5 and 10 years later, respectively. Six
      out of eight patients who underwent lung transplantation had a long postoperative
      survival. CONCLUSIONS: LAM seems to be as infrequent in Catalunya as in other
      countries, even if some cases could be misdiagnosed. Lung transplantation is
      useful in the advanced stages of the disease and, in our experience, it has
      improved respiratory insufficiency in half of the patients.

PMID- 10965486
TI  - [Genetic studies of obesity in humans].

PMID- 10965487
TI  - [Congenital errors of metabolism: cause of oxidative stress?].

PMID- 10965488
TI  - [Viral load and CD4+ lymphocyte count in the era of highly active antiretroviral
      therapy].

PMID- 10965489
TI  - [Combination of ranitidine and bismuth citrate plus 2 antibiotics in the
      eradication of Helicobacter pylori].

PMID- 10965490
TI  - [The role of the sociologist in medicine].

PMID- 10965491
TI  - B-cell epitopes of intracellular autoantigens: myth and reality.

PMID- 10965492
TI  - Structural basis of Bloom syndrome (BS) causing mutations in the BLM helicase
      domain.
AB  - BACKGROUND: Bloom syndrome (BS) is characterized by mutations within the BLM
      gene. The Bloom syndrome protein (BLM) has similarity to the RecQ subfamily of
      DNA helicases, which contain seven conserved helicase domains and share
      significant sequence and structural similarity with the Rep and PcrA DNA
      helicases. We modeled the three-dimensional structure of the BLM helicase domain
      to analyze the structural basis of BS-causing mutations. MATERIALS AND METHODS:
      The sequence alignment was performed for RecQ DNA helicases and Rep and PcrA
      helicases. The crystal structure of PcrA helicase (PDB entry 3PJR) was used as
      the template for modeling the BLM helicase domain. The model was used to infer
      the function of BLM and to analyze the effect of the mutations. RESULTS: The
      structural model with good stereochemistry of the BLM helicase domain contains
      two subdomains, 1A and 2A. The electrostatic potential of the model is highly
      negative over most of the surface, except for the cleft between subdomains 1A and
      2A which is similar to the template protein. The ATP-binding site is located
      inside the model between subdomains 1A and 2A; whereas, the DNA-binding region is
      situated at the surface cleft, with positive potential between 1A and 2A.
      CONCLUSIONS: The three-dimensional structure of the BLM helicase domain was
      modeled and applied to interpret BS-causing mutations. The mutation I841T is
      likely to weaken DNA binding, while the mutations C891R, C901Y, and Q672R
      presumably disturb the ATP binding. In addition, other critical positions are
      discussed.

PMID- 10965493
TI  - Human breast carcinoma cells express type II IL-4 receptors and are sensitive to
      antitumor activity of a chimeric IL-4-Pseudomonas exotoxin fusion protein in
      vitro and in vivo.
AB  - BACKGROUND: Human breast carcinoma cell lines express high-affinity interleukin-4
      receptors (IL-4R). We examined the expression and structure of these receptors on
      primary and cultured breast carcinoma cell lines and normal breast epithelial
      cells. We also tested the antitumor activity in vitro and in vivo of a fusion
      protein comprised of circular permuted IL-4 and truncated Pseudomonas exotoxin,
      termed IL-4(38-37)-PE38KDEL. MATERIALS AND METHODS: Eight different primary cell
      cultures and cell lines of human breast carcinomas were examined for the
      expression of IL-4R by radiolabeled binding, reverse transcription polymerase
      chain reaction (RT-PCR) and Northern analyses, and subunit structure by
      crosslinking studies. The antitumor activity of IL-4 toxin was tested in vitro by
      cytotoxicity assays and in vivo in a xenograft model in immunodeficient animals.
      RESULTS: 125I-IL-4 specifically bound to primary cell cultures and cell lines
      with a Kd ranging between 0.2 and 1 nM. Breast tumor cells were found to express
      IL-4R beta and IL-13R alpha' chains, but not IL-2R gamma c chain. These cells
      were highly sensitive to the cytotoxic effect of IL-4(38-37)-PE38KDEL. The IC50
      (concentration inhibiting protein synthesis by 50%) ranged between approximately
      0.005-1.5 nM. A normal breast epithelial cell culture was not sensitive to the
      cytotoxic activity of IL-4(38-37)-PE38KDEL. MDA-MB231 human breast carcinoma cell
      line formed a rapidly growing tumor in nude mice. Intratumor and intraperitoneal
      administration of IL-4(38-37)-PE38KDEL caused a dose dependent regression of
      established tumors. A control toxin, anti-Tac(Fv)-PE38KDEL, targeted to the IL-2
      receptor alpha chain did not cause regression of these tumors. CONCLUSIONS: These
      results suggest that IL-4(38-37)-PE38KDEL may be a useful agent for targeting of
      IL-4 receptor positive human breast carcinomas and further studies should be
      performed to explore fully its potential.

PMID- 10965494
TI  - Toxicity associated with repeated administration of first-generation adenovirus
      vectors does not occur with a helper-dependent vector.
AB  - BACKGROUND: Certain gene therapy protocols may require multiple administrations
      of vectors to achieve therapeutic benefit to the patient. This may be especially
      relevant for vectors such as adenoviral vectors that do not integrate into the
      host chromosome. Because immunocompetent animal models used for gene transfer
      studies develop neutralizing antibodies to adenoviral vectors after a single
      administration, little is known about how repeat administrations of vectors might
      affect transgene expression and vector toxicity. MATERIALS AND METHODS: We used
      mice deficient in the membrane spanning region of immunoglobulin (IgM), which do
      not develop antibodies, to evaluate the effect of repeated intravenous
      administration of first-generation and helper-dependent adenoviral vectors
      expressing human alpha 1-antitrypsin (hAAT). The duration and levels of transgene
      expression were evaluated after repeated administration of vectors. Toxicity was
      assessed by measuring the level of liver enzymes in the serum and the degrees of
      hepatocyte hypertrophy and proliferation. RESULTS: We found that previous
      administration of first-generation adenoviral vectors can alter the response to
      subsequent doses. These alterations included an increase in transgene expression
      early (within 1 and 3 days), followed by a rapid drop in expression by day 7. In
      addition, previous administrations of first-generation vectors led to an increase
      in toxicity of subsequent doses, as indicated by a rise in liver enzymes and an
      increase in hepatocyte proliferation. In contrast to first-generation vectors,
      use of the helper-dependent adenovirus vector, Ad-STK109, which contained no
      viral coding regions, did not lead to increased toxicity after multiple
      administrations. CONCLUSIONS: We conclude that the response of the host to
      adenoviral vectors can be altered after repeated administration, compared with
      the response after the initial vector dose. In addition, these experiments
      provide further evidence for the relative safety of helper-dependent adenoviral
      vectors for gene therapy, compared with first-generation vectors.

PMID- 10965495
TI  - Different roles of the CD2 and LFA-1 T-cell co-receptors for regulating
      cytotoxic, proliferative, and cytokine responses of human V gamma 9/V delta 2 T
      cells.
AB  - BACKGROUND: Human V gamma 9/V delta 2 T lymphocytes recognize nonpeptidic
      antigens in a manner distinct from the classical antigen recognition by alpha
      beta T cells. The apparent lack of major histocompatibility (MHC) restriction and
      antigen processing allows very fast responses against pathogenic insults. To
      address the potential functional requirement for accessory molecules, we
      investigated the roles of the CD2 and lymphocyte function-associated antigen
      (LFA)-1 T-cell co-receptors in antigen-induced activities of human V gamma 9/V
      delta 2 T-cell clones. MATERIALS AND METHODS: Human peripheral blood V gamma 9/V
      delta 2 T lymphocytes were cloned and their cytotoxicity against Daudi lymphoma
      was measured by a standard 51Cr-release assay. The responses of V gamma 9/V delta
      2 T lymphocytes to nonpeptidic antigens were assessed using DNA synthesis and
      cytokine ELISA assays. Monoclonal antibodies specific for various molecules with
      potential T-cell accessory functions were utilized in blocking assays. RESULTS:
      All of our V gamma 9/V delta 2 T-cell clones displayed the Th1 phenotype. The
      anti-LFA-1 antibody strongly inhibited the cytotoxicity of V gamma 9/V delta 2 T
      cells against Daudi B-cell lymphoma; whereas, it had no influence on the antigen
      induced cytokine release or proliferation. In contrast, antibodies against CD2
      and LFA-3 had no effect on the lytic activity of V gamma 9/V delta 2 T cells, but
      strongly inhibited the cytokine release and proliferation. However, the CD2-LFA-3
      interaction was not an absolute requirement for the cytokine release and the DNA
      synthetic activity of antigen-stimulated V gamma 9/V delta 2 T cells, since the
      inhibitory effect could be reversed by addition of exogenous interleukin 2 (IL
      2). CONCLUSIONS: These novel observations indicate that the signals generated by
      different accessory molecules and IL-2 can contribute in an integrated fashion to
      the regulation of V gamma 9/V delta 2 T cells. These interactions may be
      important for the effectiveness of V gamma 9/V delta 2 T-cell responses.

PMID- 10965498
TI  - Neuronal and cognitive effects of oestrogens. Introduction.

PMID- 10965497
TI  - Biochemical and immunological properties of a viral hybrid particle expressing
      the Plasmodium vivax merozoite surface protein 1 C-terminal region.
AB  - BACKGROUND: Mammalian cells expressing the small hepatitis B virus surface
      protein (HBs) secrete highly immunogenic 20 nm lipoprotein particles. Previous
      studies demonstrated that the fusion of foreign sequences into certain regions of
      HBs leads to chimeric particles carrying epitopes for the foreign peptide, as
      well as for HBs. The present study investigates immunologic and biochemical
      properties of the fusion of the C-terminal region of the merozoite surface 1
      protein of P. vivax, the most widely distributed human malaria parasite, and HBs
      (PvMSP1(19)-HBs). MATERIALS AND METHODS: COS7 cells were transfected with a
      plasmid coding for PvMSP1(19)-HBs. The hybrid products were analyzed by density
      gradient centrifugation and electron microscopy or detected by metabolic labeling
      and immunoprecipitation with anti-HBs and patient-derived anti-P. vivax serum.
      Mice were immunized with the vector and the antibody response was checked by
      ELISA. RESULTS: The fusion PvMSP1(19)-HBs formed particles of 20-45 nm size,
      which were secreted from COS7 cells. The particles were immunoprecipitable with
      anti-HBs and serum of different P. vivax-positive individuals. Immunization of
      mice with the construct as a genetic vaccine showed that antibodies were raised
      mostly against the PvMSP1(19) domain and recognized the native protein.
      CONCLUSION: Due to its biochemical and antigenic properties, the hybrid particle
      will be useful in future vaccine trials against the asexual blood stages of P.
      vivax as a genetic and/or a proteic subunit candidate.

PMID- 10965496
TI  - Altered expression of the cell cycle regulatory molecules pRb, p53 and MDM2 exert
      a synergetic effect on tumor growth and chromosomal instability in non-small cell
      lung carcinomas (NSCLCs).
AB  - BACKGROUND: Recent in vitro studies provide evidence that the cell cycle
      molecules pRb, p53 and MDM2 form a tightly regulated protein network. In this
      study, we examined the relationship of this protein network in a series of non
      small cell lung carcinomas (NSCLCs), with the kinetic parameters, including
      proliferative activity or proliferation index (PI) and apoptotic index (AI), and
      ploidy status of the tumors. MATERIAL AND METHODS: A total of 87 NSCLCs were
      examined using immunohistochemical and molecular methods in order to estimate the
      status of the pRb-p53-MDM2 network. The kinetic parameters and the ploidy status
      of the tumors were assessed by in situ assays. The possible associations between
      alterations of the network, kinetic parameters and ploidy status of the
      carcinomas were assessed with a series of statistical methods. RESULTS: Aberrant
      expression of pRb (Ab) and overexpression of p53 (P) and MDM2 (P) proteins were
      observed in 39%, 57%, and 68% of the carcinomas, respectively. The comprehensive
      analysis revealed that concurrent alterations in all three cell cycle regulatory
      molecules were the most frequent pattern, pRb(Ab)/p53(P)/MDM2(P); this "full
      abnormal" phenotype represented approximately 27% of the cases. This
      immunoprofile obtained the highest PI/AI value; whereas, the "normal" phenotype
      was the lowest one (p = 0.004). Furthermore, the pattern pRb(Ab)/p53(P)/MDM2(P)
      acquired the highest PI (p < 0.001) and lowest AI (p < 0.001) scores.
      Interestingly, the groups of carcinomas with impaired expression of one or two
      molecules attained PI/AI ratio values clustered in a narrow range placed in the
      middle of the scores exhibited by the "normal" and "full abnormal" phenotypes.
      These tumors had significantly lower AI, but similar PI values, compared with
      those noticed in the normal pattern. In addition, it was observed that the
      pRb(Ab)/p53(P)/MDM2(P) phenotype was also significantly associated with
      aneuploidy (p = 0.002) and a tendency was observed when the expression of two
      components was altered (p = 0.055). CONCLUSIONS: Our findings suggest that
      simultaneous deregulation of all members of the pRb-p53-MDM2 network confers an
      additive effect on tumor growth. The apoptotic pathway seems to be more
      susceptible to its defects than the cell proliferation machinery. The findings of
      the ploidy analysis, which are in parallel with those regarding the proliferative
      activity and the apoptotic rate study, further support the concept that these
      molecules constitute a tightly regulated network participating in cell cycle
      control and chromosomal stability.

PMID- 10965499
TI  - Mechanism of oestrogen signalling with particular reference to the role of ER
      beta in the central nervous system.
AB  - The discovery of a second oestrogen receptor (ER), ER beta, has drastically
      changed our view of oestrogen action. Since the two ERs, ER alpha and ER beta,
      have somewhat different tissue and cellular distribution as well as ligand
      binding specificity the possibility exists that they have different biological
      roles. Indeed, several observations seem to indicate that they may even have
      opposite effects so that ER beta diminishes the activity of ER alpha. The CNS
      contains both ER alpha and ER beta and it is conceivable that they may have
      specific and individual roles in oestrogen signalling in the brain.

PMID- 10965500
TI  - Oestrogen receptor function at classical and alternative response elements.
AB  - The oestrogen receptor (ER), bound to classical response elements (EREs) in the
      promoter of target genes, activates transcription by recruiting coactivator
      proteins. We will describe structural studies that show that oestrogens allow the
      formation of a hydrophobic cleft on the surface of the ER that serves as a
      docking site for coactivators. Anti-oestrogens displace part of the receptor,
      which then occludes the site, blocking coactivator access. In addition to
      activating at classical EREs, the ER activates transcription at alternative
      elements such as AP-1 sites. These bind the Jun/Fos proteins but not ER.
      Interestingly both oestrogen and tamoxifen activate transcription at AP-1 sites.
      We propose a mechanism whereby oestrogen and anti-oestrogen allow ER to activate
      transcription from alternative response elements. ER binds to the coactivators,
      CBP and GRIP1, that have been recruited by Jun/Fos and through this contact
      'triggers' these coactivators into full activity. In this circumstance the ER is
      part of the coactivator complex for Jun/Fos.

PMID- 10965501
TI  - Nuclear receptor versus plasma membrane oestrogen receptor.
AB  - The co-existence of both plasma membrane and nuclear oestrogen receptors has
      changed our thinking about the mechanisms of the actions of this sex steroid. To
      date, however, the plasma membrane receptor has not been isolated. However, many
      emerging data implicate this receptor in the rapid, non-genomic effects of
      oestrogen, and this is seen when the membrane receptor effects a variety of
      signal transduction events. Although discrete actions of oestradiol could be
      mediated through the plasma membrane receptor, there is probably often a
      coordination of effects mediated through both receptors, perpetuating and
      magnifying the cell biological effects of the steroid.

PMID- 10965502
TI  - Novel sites and mechanisms of oestrogen action in the brain.
AB  - We are investigating novel, non-transcriptionally mediated mechanisms that may
      contribute to the differentiative effects of oestrogen in developing forebrain
      neurons. Recent findings in the cerebral cortex document that 17 alpha- and 17
      beta-oestradiol elicit rapid and sustained activation of the Ras-Raf-MAP kinase
      cascade, a major growth factor signalling pathway. Using oestrogen receptor (ER)
      alpha knockout (ERKO) mice, we addressed the identity of the receptor mediating
      activation of the MAP kinase cascade. 17 beta-oestradiol increased B-Raf activity
      and MEK-dependent ERK phosphorylation in explants of wild-type and ERKO cerebral
      cortex. Although neither the ER alpha-selective ligand, 16 alpha-iodo-17 beta
      oestradiol (16 alpha-IE2) nor the ER beta-selective ligand, genistein, elicited
      ERK phosphorylation, as little as 0.1 nM 17 beta-oestradiol did so. Moreover, 16
      alpha-IE2 acted as an inhibitory modulator of ERK activation, and the ER
      antagonist ICI 182 780 blocked oestradiol action only in wild-type cultures.
      These data suggest that neither ER alpha nor ER beta mediate activation of the
      MAP kinase cascade. A putative, novel, oestradiol-sensitive and ICI 182 780
      insensitive receptor, designated ER-X may, rather, be involved. Association of ER
      X with flotillin, the neuronal homologue of the caveolar protein, caveolin,
      places ER-X within plasma membrane caveolae and supports the hypothesis that a
      membrane-associated ER may mediate rapid oestrogen activation of the MAP kinase
      cascade.

PMID- 10965503
TI  - Oestrogen modulation of noradrenaline neurotransmission.
AB  - Noradrenaline (NA) exerts an important neuromodulatory role within diverse
      neuronal networks and is also likely to be a target for oestrogen in the brain.
      Distinct, highly organized sub-populations of brainstem NA neurons express
      oestrogen receptors (ERs) and some of these display species differences. A number
      of genes expressed by NA neurons, ranging from transcription factors to co
      released neuropeptides, are influenced by oestrogen and may have roles in the
      predominant enhancement in NA activity in response to oestrogen. The effects of
      oestrogen on genes involved directly in NA biosynthesis are less clear, although
      promoter transgenic work suggests oestrogen to have a powerful influence upon
      tyrosine hydroxylase gene transcription. In addition to direct actions on NA
      neurons, evidence suggests that oestrogen also regulates adrenergic receptor
      expression and function within the ER-rich hypothalamus as well as the cerebral
      cortex. Together, these investigations point to a multifaceted pre- and
      postsynaptic regulation of NA transmission by oestrogen. While the hypothalamic
      neuronal networks controlling reproduction remain the principal site of
      investigation of oestrogen regulated NA transmission, the role of oestrogen and
      NA and their potential interactions in cortical functioning are becoming of equal
      interest.

PMID- 10965504
TI  - Oestrogen and the cholinergic hypothesis: implications for oestrogen replacement
      therapy in postmenopausal women.
AB  - Cholinergic deficits in the basal forebrain, hippocampus and cortex are thought
      to contribute to the risk and severity of cognitive decline associated with
      ageing and Alzheimer's disease. Work in our laboratory has demonstrated that in
      rats, basal forebrain cholinergic neurons are affected by physiological
      fluctuations in circulating oestrogen and progesterone, and that long-term loss
      of ovarian function produces decreases in cholinergic parameters and nerve growth
      factor receptor (trkA) mRNA beyond the effects of normal ageing. Conversely,
      short-term treatment with oestrogen or oestrogen plus progesterone produces
      increases in cholinergic parameters and trkA, as well as increases in potassium
      stimulated acetylcholine release, that are consistent with an increase in basal
      forebrain cholinergic function. These findings are consistent with recent studies
      showing the ability of oestrogen and progesterone replacement to enhance spatial
      memory and reduce performance deficits associated with hippocampal cholinergic
      impairment. We hypothesize that similar effects of the ovarian hormones on basal
      forebrain cholinergic neurons in humans may contribute to the effects of hormone
      replacement on cognitive processes that have recently been described, and to the
      ability of oestrogen replacement to reduce the risk and severity of Alzheimer's
      related dementia in postmenopausal women.

PMID- 10965505
TI  - Ovarian steroid action in the serotonin neural system of macaques.
AB  - The serotonin neural system plays an important role in cognitive, emotional and
      endocrine processes. If the ovarian hormones, oestrogen and progesterone, alter
      serotonin neural transmission, then functional changes in all of these systems
      would follow. Therefore, information on the effects of oestrogen and progesterone
      at a molecular level in the serotonin neural system was sought using non-human
      primates. Serotonin neurons express nuclear oestrogen receptor beta (ER beta) and
      progesterone receptors (PRs) which are gene transcription factors. Within
      serotonin neurons, the regulation of three genes related to serotonin
      neurotransmission was examined. The mRNA for tryptophan hydroxylase (TPH), the
      committal enzyme in serotonin synthesis, increased significantly with oestrogen
      treatment and remained elevated when progesterone was added to the oestrogen
      regimen. Serotonin reuptake transporter (SERT) mRNA decreased significantly with
      oestrogen treatment and addition of progesterone had no further effect. 5-HT1A
      autoreceptor mRNA decreased significantly with oestrogen treatment and addition
      of progesterone caused a further decrease. Little or no regulation of
      postsynaptic 5-HT1A, 5-HT2A or 5-HT2C receptor mRNAs was observed in hypothalamic
      target neurons. TPH protein is increased by oestrogen treatment and remains
      elevated with addition of progesterone in a manner similar to TPH mRNA.
      Medroxyprogesterone (MPA) blocked the stimulatory effect of oestrogen on TPH
      protein and tamoxifen reduced TPH protein levels below that observed in spayed
      monkeys. Together these data indicate that ovarian hormones and their synthetic
      analogues could modify cognitive and autonomic neural functions by acting on the
      serotonin neural pathway.

PMID- 10965506
TI  - Oestrogen effects on dopaminergic function in striatum.
AB  - Experiments involving the use of behavioural, neurochemical and
      electrophysiological methods to explore the mechanisms mediating the effects of
      oestrogen on dopaminergic activity in the striatum on the female rat are
      described. Results have shown that oestrogen influences the activity of striatal
      dopamine terminals and dopamine-mediated behaviours in the female rat. These are
      rapid effects of oestrogen in the striatum, and are thought to be mediated by a
      novel membrane-associated receptor. How these novel effects of oestrogen may
      affect naturally occurring behaviours in the rat will be discussed.

PMID- 10965508
TI  - Effects of oestradiol on hippocampal circuitry.
AB  - Oestradiol produces structural and functional changes in hippocampal circuitry of
      adult female rats. The density of both dendritic spines and axospinous synapses
      on hippocampal CA1 pyramidal cells is regulated by oestradiol. Additionally,
      oestradiol-induced differences in synaptic connectivity are paralleled by changes
      in NMDA receptor binding, immunoreactivity for NMDA receptors and sensitivity to
      NMDA receptor-mediated synaptic input. Curiously, while oestradiol effects are
      observed in CA1 pyramidal cells, most evidence indicates that these cells lack
      genomic oestradiol receptors. In contrast, at least some inhibitory neurons in
      CA1 do express oestradiol receptors. Others' in vitro studies suggest that
      oestradiol-induced increases in spine density require an initial decrease in
      inhibitory (GABAergic) drive onto pyramidal cells. We have used single and double
      label immunohistochemistry for c-Fos (as a measure of neuronal activation) and
      glutamic acid decarboxylase 65 (as a marker for inhibitory circuitry) to
      determine: (1) which hippocampal neuronal populations are activated by oestradiol
      and the time-course of this activation, as well as (2) whether oestradiol affects
      inhibitory circuitry in vivo as it does in vitro. Our findings are consistent
      with the suggestion that oestradiol increases dendritic spine density through a
      mechanism involving disinhibition of pyramidal cells.

PMID- 10965507
TI  - Oestrogen effects in olivo-cerebellar and hippocampal circuits.
AB  - 17 beta-oestradiol (E2) is known to exert activating effects on CNS excitability,
      which are in part mediated by increases in glutamate responses, as we have shown
      in cerebellum. In addition, this steroid is known to facilitate rapid, rhythmic
      limb movement. Because the inferior olive is believed to be a timer of rapid
      movement, we have investigated effects of E2 on patterns of discharge recorded
      from dorsal accessory olive (DAO) using chronically implanted microwires. E2
      increases the frequency of rhythmic olivary discharge as well as the number of
      synchronized neurons in association with facilitation of rhythmic limb and
      vibrissae movement. One possible mechanism for this effect is via an increase in
      gap junction proteins, as olivary cells are electrotonically coupled. Levels of
      connexin 32 (Cx32) and the dendritic lamellar body, both markers for gap junction
      associated proteins, are increased threefold after 48 h E2 exposure (2
      micrograms, i.p.), compared to control in both ventral medulla and hippocampal
      neurons. Gap junction conductance has also been shown to be decreased by gamma
      aminobutyric acid (GABA)ergic input. For this reason, we tested effects of 48 h
      E2 treatment on GABAA receptor subunit proteins and GABAergic synaptic current.
      E2 increased levels of the alpha 4 subunit in hippocampus via an increase in the
      GABA-modulatory progesterone metabolite 3 alpha-OH-5 alpha-pregnan-20-one. This
      effect was correlated with a decrease in decay time of tetrodotoxin-resistant
      miniature inhibitory postsynaptic currents (mIPSCs) recorded from pyramidal cells
      in CA1 hippocampus, an effect which would tend to reduce total GABA inhibition.
      In sum, these effects of E2 are consistent with the concept that E2 exerts
      primarily activating effects on CNS excitability.

PMID- 10965509
TI  - Oestrogen and cognitive function throughout the female lifespan.
AB  - Evidence that oestrogen helps to maintain verbal memory in women comes from
      several sources. Studies that have tested cognitive functioning at different
      phases of the menstrual cycle have found few differences, perhaps because
      oestrogen levels are sufficiently high, albeit variable, during all cycle phases.
      Experimental studies in postmenopausal women have generally found a protective
      effect of oestrogen, specifically on verbal memory. Results of several large,
      longitudinal studies that have become available recently have also demonstrated
      that women who were oestrogen users performed better on certain tests of
      cognitive function than non-users of similar age. On the basis of this body of
      evidence, it is possible to conclude that oestrogen may attenuate or prevent the
      decline in aspects of memory that occur with normal ageing in women.

PMID- 10965510
TI  - Neuroprotective effects of phenolic A ring oestrogens.
AB  - We have formulated the 'phenolic A ring hypothesis' for the neuroprotective
      effects of oestrogens based upon several observations: (i) structure-activity
      relationships show that a phenolic A ring and at least two additional rings are
      required for neuroprotection while oestrogenicity requirements are more
      stringent; (ii) neuroprotection with phenolic A ring compounds occurs in cells
      that lack oestrogen receptors and are not antagonized by anti-oestrogens; (iii)
      phenolic A ring compounds rapidly activate a variety of signal transduction
      pathways that are known to be involved in cell homeostasis; and (iv) in vivo,
      treatment with oestrogens results in a neuronal type-independent neuronal
      protection from ischaemic insult. Potential mechanisms of actions that may be
      involved in the neuroprotective effects of phenolic A ring compounds are: (i)
      oestrogen redox cycling that potently inhibits oxidative stress; (ii)
      interactions with signal transduction pathways including the transcription factor
      cAMP response element binding protein; and (iii) induction of anti-apoptotic
      proteins. These signalling pathways may individually or collectively contribute
      to the plethora of neuronal cell types that are protected from a variety of
      insults by oestrogen-like compounds.

PMID- 10965511
TI  - The female sex hormone oestrogen as neuroprotectant: activities at various
      levels.
AB  - The female sex hormone oestradiol (oestrogen) is a steroidal compound that binds
      to specific intracellular receptors which act as transcription factors. Oestrogen
      displays many of its effects by the classical mode of action through receptor
      binding, transactivation and binding to consensus oestrogen response elements on
      DNA. Although the primary role of oestrogen as an ovarian steroid was thought to
      be the regulation of sex differentiation and maturation, since oestrogen
      receptors are expressed in a variety of other tissues besides sex organs,
      oestrogen is believed to exert multiple activities in several target sites
      throughout the body, including the nervous system. In the brain oestrogens have
      multiple activities. Potential neuroprotective functions of oestrogens are being
      intensively studied and it is becoming increasingly clear that oestrogens are (1)
      neuroprotective hormones acting via oestrogen receptor-dependent pathways at the
      genomic level and (2) neuroprotective steroidal structures acting independently
      of the activation of specific oestrogen receptors. One striking activity of the
      molecule oestradiol is its intrinsic antioxidant activity which makes it a
      potential chemical shield for neurons. Nerve cells frequently encounter oxidative
      challenges during the normal physiology, but also under pathophysiological
      conditions. Oxidative stress has been implicated in a variety of
      neurodegenerative disorders including amyotrophic lateral sclerosis, Parkinson's
      disease and Alzheimer's disease. It is important to stress that the antioxidant
      neuroprotective activity of oestrogens is independent of oestrogen receptor
      activation, since oestrogen derivatives and aromatic alcohols that do not bind to
      oestrogen receptors share the same antioxidant neuroprotective activity. Although
      this effect of oestrogens can clearly be separated from oestrogen receptor
      binding, oestrogens may interact with intracellular signalling pathways, such as
      the mitogen activated protein kinase, cyclic AMP pathways, and with the activity
      of the redox-sensitive transcription factor NF-kappa B.

PMID- 10965512
TI  - Neurohormonal signalling pathways and the regulation of Alzheimer beta-amyloid
      metabolism.
AB  - Alzheimer's disease (AD) is characterized by the intracranial accumulation of the
      4 kDa amyloid beta peptide (A beta), following proteolysis of a approximately 700
      amino acid, integral membrane precursor, the amyloid beta precursor protein
      (APP). The best evidence causally linking APP to AD has been provided by the
      discovery of mutations within the APP coding sequence that segregate with disease
      phenotypes in autosomal dominant forms of familial AD (FAD). Though FAD is rare
      (< 10% of all AD), the hallmark features--amyloid plaques, neurofibrillary
      tangles, synaptic and neuronal loss, neurotransmitter deficits, dementia--are
      indistinguishable when FAD is compared with typical, common, 'non-familial', or
      sporadic AD (SAD). Studies of some clinically relevant mutant APP molecules from
      FAD families have yielded evidence that APP mutations can lead to enhanced
      generation or aggregability of A beta, consistent with a pathogenic role in AD.
      Other genetic loci for FAD have been discovered which are distinct from the
      immediate regulatory and coding regions of the APP gene, indicating that defects
      in molecules other than APP can also specify cerebral amyloidogenesis and FAD. To
      date, all APP and non-APP FAD mutations can be demonstrated to have the common
      feature of promoting amyloidogenesis of A beta. Epidemiological studies indicate
      that postmenopausal women on oestrogen hormone replacement therapy (HRT) have
      their relative risk of developing SAD diminished by about one-third as compared
      with age-matched women not receiving HRT. Because of the key role of cerebral A
      beta accumulation in initiating AD pathology, it is most attractive that
      oestradiol might modulate SAD risk or age-at-onset by inhibiting A beta
      accumulation. A possible mechanistic basis for such a scenario is reviewed here.

PMID- 10965513
TI  - Oestrogens and dementia.
AB  - The decline in circulating oestrogen concentrations that occurs after the
      menopause has the potential to impact Alzheimer's disease and other forms of
      dementia. Relevant actions include neurotrophic and neuroprotective effects;
      effects on acetylcholine and other neurotransmitters; and effects on proteins
      implicated in Alzheimer's disease pathogenesis. Since 1990, 14 case-control and
      cohort studies have considered the relation between postmenopausal oestrogen
      therapy and Alzheimer's disease. Most, but not all, report that oestrogen therapy
      is associated with a reduced Alzheimer risk of approximately one-half. Almost no
      epidemiological data address the potential link between oestrogen and other forms
      of dementia. Several small interventional trials have considered whether
      oestrogen might improve cognitive function of women with Alzheimer's disease.
      Data, however, are limited, and there is no compelling evidence that the short
      term use of oestrogen monotherapy has a substantial impact on dementia symptoms.
      In summary, the use of oestrogen to reduce Alzheimer risk is biologically
      credible, and the preponderance of epidemiological evidence suggests that
      oestrogen therapy is indeed protective. This potentially important role of
      oestrogens for the primary prevention of Alzheimer's disease remains to be
      verified through well-designed randomized controlled trials.

PMID- 10965514
TI  - Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic
      effectiveness and development of side effects.
AB  - Several studies suggest that dietary supplementation with antioxidants can
      influence the response to chemotherapy as well as the development of adverse side
      effects that results from treatment with antineoplastic agents. Administration of
      antineoplastic agents results in oxidative stress, i.e., the production of free
      radicals and other reactive oxygen species (ROS). Oxidative stress reduces the
      rate of cell proliferation, and that occurring during chemotherapy may interfere
      with the cytotoxic effects of antineoplastic drugs, which depend on rapid
      proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and
      may enhance the anticancer effects of chemotherapy. For some supplements,
      activities beyond their antioxidant properties, such as inhibition of
      topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or
      contribute to certain side effects that are common to many anticancer drugs, such
      as gastrointestinal toxicity and mutagenesis. ROS also contribute to side effects
      that occur only with individual agents, such as doxorubicin-induced
      cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary
      fibrosis. Antioxidants can reduce or prevent many of these side effects, and for
      some supplements the protective effect results from activities other than their
      antioxidant properties. Certain side effects, however, such as alopecia and
      myelosuppression, are not prevented by antioxidants, and agents that interfere
      with these side effects may also interfere with the anticancer effects of
      chemotherapy.

PMID- 10965515
TI  - Mechanisms linking diet and colorectal cancer: the possible role of insulin
      resistance.
AB  - Diet is clearly implicated in the origin of colorectal cancer, with risk factors
      for the disease including reduced consumption of vegetables, fiber, and starch
      and increased consumption of red meat and animal fat. Several hypotheses have
      been developed to explain these associations. Most recently, McKeown-Eyssen and
      Giovannucci noted the similarity of the risk factors for colorectal cancer and
      those for insulin resistance and suggested that insulin resistance leads to
      colorectal cancer through the growth-promoting effect of elevated levels of
      insulin, glucose, or triglycerides. We briefly review the evidence from
      observational, epidemiological, and experimental animal studies linking diet with
      insulin resistance and colorectal cancer. The evidence suggests that diets high
      in energy and saturated fat and with high glycemic index carbohydrate and low
      levels of fiber and n-3 fatty acids lead to insulin resistance with
      hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. We then consider how
      insulin, the related insulin-like growth factors, triglycerides, and
      nonesterified fatty acids could lead to increased growth of colon cancer
      precursor lesions and the development of colorectal cancer. Finally, we consider
      the implications of this scheme on possible future research directions, including
      studies of satiety and clinical tests of the importance of insulin resistance in
      the colon carcinogenesis process.

PMID- 10965516
TI  - Yogurt consumption does not enhance immune function in healthy premenopausal
      women.
AB  - Fermented milk products may protect against breast cancer by stimulating
      immunologic activity. Twenty-five women [24.0 +/- 0.7 (SE) yr] were assigned
      randomly to two groups: control (n = 12) and yogurt treatment (n = 13). Controls
      refrained from yogurt products for three months, whereas the yogurt treatment
      group consumed two cups (454 g/day) of commercially produced yogurt for three
      consecutive months. Prior yogurt consumption did not exceed 4-6 cups/mo, and
      subjects consumed their usual diet during the study. Three-day diet records and
      fasting midluteal blood samples were obtained during subjects' first, second, and
      fourth menstrual cycles (baseline, Month 1, and Month 3, respectively).
      Macronutrient intakes differed between groups only for carbohydrate. Calcium
      intake increased for yogurt consumers during intervention. Lymphocyte
      proliferation induced by concanavalin A, phytohemagglutinin, and pokeweed
      mitogen, interleukin 2 production, and cytotoxic T lymphocyte-mediated
      cytotoxicity was assessed after baseline and Months 1 and 3 for both groups. No
      significant immune differences between the control and yogurt treatment group
      were observed for concanavalin A, phytohemagglutinin, pokeweed mitogen,
      interleukin-2, or cytotoxicity. In conclusion, three months of yogurt consumption
      did not enhance ex vivo cell-mediated immune function in young women.

PMID- 10965517
TI  - Prognostic factors in advanced gastrointestinal cancer patients with weight loss.
AB  - There are few reports on factors that determine survival in advanced
      gastrointestinal cancer with weight loss. In these patients (n = 91, median
      weight loss 16.6%), we prospectively examined the importance of metastatic
      spread, anthropometry, blood parameters, Karnofsky performance status, appetite,
      and the acute-phase response as predictors of survival. Survival was calculated
      from date of assessment to the most recent clinic attendance (> or = 30 mo) or
      until death. On multivariate analysis, metastatic spread (p < 0.05), Karnofsky
      performance status (p < 0.01), and C-reactive protein concentration (p < 0.001)
      had independent prognostic value. In locally advanced disease (n = 64), Karnofsky
      performance status and C-reactive protein concentration remained significant.
      There was a significantly lower survival in patients with an acute-phase response
      (median 136 days) than in patients with no response (median 466 days; p < 0.01).
      Performance status and the acute-phase response are associated, independent of
      weight loss, with survival duration in advanced gastrointestinal cancer patients.

PMID- 10965518
TI  - Plasma and tissue levels of tea catechins in rats and mice during chronic
      consumption of green tea polyphenols.
AB  - To understand the relationship between tea consumption and its biological
      effects, plasma and tissue levels of (-)-epigallocatechin-3-gallate (EGCG), (-)
      epigallocatechin (EGC), and (-)-epicatechin (EC) were measured after rats and
      mice were given a 0.6% green tea polyphenol preparation as the drinking fluid for
      different periods of time. EGC and EC levels in rat plasma increased over time
      and reached peak values (3 times the Day 1 values) on Day 14. Then the plasma
      levels of tea catechins decreased, to Day 1 values on Day 28. The plasma
      concentrations of EGCG were much lower than those of EGC or EC. High levels of
      EGC and EC were found in urine, whereas high levels of EGCG were found in feces.
      The changes in the urinary and fecal excretions of tea catechins could not
      account for the above-described changes in the plasma levels. The amounts of
      catechins in different tissues reflected the ingestion, absorption, and excretion
      pattern. When the green tea polyphenol preparation was given to mice, the
      "increase-and-then-decrease" pattern of catechin levels was also observed in the
      plasma, lung, and liver; the EGCG levels were much higher than in the rats. The
      results suggest that consumption of tea by rodents could induce adaptive
      responses affecting blood and tissue levels of tea catechins with time and that
      investigation of a similar phenomenon in humans is warranted.

PMID- 10965519
TI  - Genistein and curcumin block TGF-beta 1-induced u-PA expression and migratory and
      invasive phenotype in mouse epidermal keratinocytes.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) stimulates migration/invasion of
      mouse transformed keratinocytes and increases urokinase (u-PA)
      expression/secretion. In this report, we analyzed the biological behavior of two
      naturally occurring inhibitors of protein tyrosine kinases, genistein and
      curcumin, that could abrogate the enhancement of u-PA levels induced by TGF-beta
      1 in transformed keratinocytes. Our results showed that genistein and curcumin
      blocked this response in a dose-dependent manner and also inhibited the TGF-beta
      1-induced synthesis of fibronectin, an early responsive gene to the growth
      factor. Both compounds also reduced TGF-beta 1-stimulated cell migration and
      invasiveness. These results suggest that a tyrosine kinase-signaling pathway
      should be involved in TGF-beta 1-mediated increased malignancy of transformed
      keratinocytes and that genistein and curcumin could play an important role in
      inhibiting tumor progression.

PMID- 10965520
TI  - Fate of the mushroom hydrazine agaritine in the rat and mouse.
AB  - The fate of the mushroom hydrazine [14C]agaritine was investigated in the mouse
      and rat strains previously employed in carcinogenicity studies with the edible
      mushroom Agaricus bisporus. Agaritine was rapidly absorbed in both species,
      achieving higher blood levels in the mouse, but with similar area under the
      curve. Covalent binding of agaritine material to proteins was detected only in
      the liver and kidney, but the extent of binding was the same in the rat and
      mouse. Most of the radioactivity was excreted during the first 24 hours in both
      animal species: in the rat it was distributed equally between urine and feces,
      whereas in the mouse more of the radioactivity was excreted in the urine. No
      qualitative differences in the metabolic profile were evident, but quantitative
      differences were observed. Treatment of the urine with deconjugating enzymes did
      not reveal the presence of any conjugates. Agaritine, N'-acetyl-4
      (hydroxymethyl)phenylhydrazine, and 4-(hydroxymethyl)benzene diazonium ion were
      not detected in the urine or in the plasma of either species. No mutagens or
      promutagens were detected by the Ames mutagenicity assay in the urine of either
      species after exposure to agaritine. Repeated administration of agaritine to rats
      and mice did not alter the urinary metabolic profile and excretion of
      radioactivity. Similarly, feeding mice a raw mushroom diet, according to the
      protocol employed in the carcinogenicity studies, did not modulate the excretion
      of radioactivity or the urinary metabolic pattern. No major species differences
      in the fate of agaritine in rat and mouse were noted that could provide a
      rationale for the carcinogenicity of A. bisporus in the mouse, but not in the
      rat.

PMID- 10965521
TI  - Modulation of liver microsomal monooxygenase system by dietary n-6/n-3 ratios in
      rat hepatocarcinogenesis.
AB  - This study was designed to determine the effects of dietary n-3/n-6 fatty acid
      ratios on preneoplastic foci and the microsomal monooxygenase system in rat
      hepatocarcinogenesis. Male Sprague-Dawley rats were fed four kinds of diets
      containing 15% (wt/wt) fat with different n-6/n-3 ratios: low ratio (> or = 1.0)
      with tuna oil, low ratio (> or = 1.0) with perilla oil, moderate ratio (< or =
      4.0), and high ratio (< or = 10.0). Hepatocarcinogenesis was induced by
      diethylnitrosamine and partial hepatectomy. The moderate ratio diet decreased
      significantly the area and number of placental glutathione S-transferase-positive
      foci compared with the high ratio diet and low ratio diet with perilla oil. The
      fatty acid composition of microsomal membrane varied extensively, reflecting the
      dietary n-6/n-3 ratios. Liver microsomal lipid peroxidation was significantly
      decreased in the group fed the low ratio diet with tuna oil compared with the
      moderate and high ratio groups. Glucose-6-phosphatase activity, which reflects
      membrane stability, was significantly higher in the low ratio groups than in the
      high ratio group. The monooxygenase activities were increased significantly in
      the moderate ratio group compared with the high ratio group. These results
      suggest that a moderate n-6/n-3 ratio (< or = 4.0) may be the most effective in
      decreasing preneoplastic foci by elevating the monooxygenase activities and n-3
      fatty acids in fish oil may have a protective effect by lowering the lipid
      peroxidation and stabilizing the microsomal membrane during rat
      hepatocarcinogenesis.

PMID- 10965522
TI  - Tannins protect against skin tumor promotion induced by ultraviolet-B radiation
      in hairless mice.
AB  - We recently showed that Tarapod tannic acid (TA), a hydrolyzable tannin extracted
      from the pods of the Tara tree (Caesalpinia spinosa), was more effective than
      other tannins tested at inhibiting ultraviolet-B (UV-B)-stimulated hydrogen
      peroxide activity (an indirect measure of free radicals) in the skin of hairless
      mice. We also found that Tarapod TA inhibited UV-B-induced ornithine
      decarboxylase activity and UV-B-stimulated DNA synthesis, two biochemical markers
      linked to the skin tumor-promoting ability of this physical carcinogen. For this
      reason, we examined the effect of topical application, force feeding (gavage),
      and intraperitoneal injections of Tarapod TA on mouse skin chronically treated
      with UV-B light. Mice were initiated by a single topical application of 7,12
      dimethylbenz[a]anthracene (50 nmol) and promoted by two weekly treatments with UV
      B light (250 mJ/cm2) for 25 weeks. Topical application of Tarapod TA, 20 minutes
      before irradiation, resulted in a dose-dependent inhibition of tumor incidence
      (number of mice with tumors) and tumor yield (number of tumors/mouse), with 8 mg
      of TA inhibiting tumor yield by 70% at Week 25. Intraperitoneal injections of low
      doses (10 mg/kg mouse body wt), but not of high doses (25 mg/kg body wt), of TA
      afforded protection against UV-B-induced papillomas. However, the protection by
      intraperitoneal injection was lower than that observed by topical application: 10
      mg/kg body wt of TA reduced tumor yield by 55%. The force feeding of 10 mg of
      Tarapod TA before irradiation failed to significantly inhibit the yield of tumors
      at the end of the experiment but delayed tumor appearance by six weeks. These
      results suggest that plant tannins administered topically or injected
      intraperitoneally reduce the tumor-promoting effects of UV-B radiation and thus
      could be useful photoprotectants.

PMID- 10965523
TI  - Inhibitory effects of crude salts on the induction and development of colonic
      aberrant crypt foci in F-344 rats given azoxymethane.
AB  - The present study was designed to investigate the modifying effects of dietary
      exposure to NaCl and four kinds of crude salts on the induction and development
      of aberrant crypt foci in Fischer 344 rats. A total of 57 male rats were divided
      into five groups at six weeks of age, and all were given weekly injections of
      azoxymethane (15 mg/kg body wt s.c.) for three weeks. Group 1 was fed a normal
      diet throughout the experiment as control group. Groups 2, 3, 4, and 5 were fed
      diets containing 4.4% pure NaCl, 4.4% cooking salt, 4.4% rock salt, and 4.4%
      beach salt, respectively, from one week before the first azoxymethane dosing. The
      mean numbers of aberrant crypt foci and aberrant crypts per colon were
      significantly lower in Groups 3-5 than in Group 1 (p < 0.01). The present results
      suggest that the other mineral components (e.g., calcium and magnesium) of these
      crude salts, rather than pure NaCl, may be chemopreventive agents for colonic
      tumorigenesis.

PMID- 10965524
TI  - beta-Carotene fails to act as a tumor promoter, induces RAR expression, and
      prevents carcinoma formation in a two-stage model of skin carcinogenesis in male
      Sencar mice.
AB  - Clinical trials have shown a significant increase in incidence of lung cancer
      among smokers and asbestos workers supplemented with beta-carotene, suggesting a
      tumor-promoting activity for this agent. We set out to test possible tumor
      promoting and chemopreventive activities of dietary and topical beta-carotene in
      the two-stage 7,12-dimethylbenz[a]anthracene-12-O-tetradecanoylphorbol 13-acetate
      (TPA) model of mouse skin carcinogenesis. In the first study, the effects of
      three levels of dietary beta-carotene (6, 60, and 600 micrograms/g purified diet
      containing no other retinoid or carotenoid) were assessed over a period of 42
      weeks. Carcinoma yield was reduced by approximately 50% in the 600 micrograms/g
      diet group (mean 0.22 carcinomas/mouse) compared with the 6 micrograms/g diet
      group (mean 0.44 carcinomas/mouse, p = 0.003). The 60 micrograms/g diet group
      showed a pattern of inhibition similar to the 600 micrograms/g diet group. A
      protective effect (25% reduction) of beta-carotene (in the 600 micrograms/g diet
      group) on papilloma formation was also found. However, the intermediate 60
      micrograms/g diet group showed the same incidence as the low 6 micrograms/g diet
      group. This points to a lack of correlation between papilloma and carcinoma
      incidence, as we also found in previous work on dietary retinoids and
      carotenoids. The purpose of the second study was to assess whether topical beta
      carotene (2 micrograms) has tumor-promoting or chemopreventive activity in the
      two-stage protocol. In the absence of TPA, beta-carotene had no significant tumor
      promoting activity. Instead, papilloma yield induced by TPA was decreased by
      topical beta-carotene from an average of 20 to approximately 10 papillomas/mouse
      (p = 2.5 x 10(-7)). The effect of topical beta-carotene persisted beyond the
      treatment period (Week 24) until the termination of the study at Week 42. Western
      blot analysis of mouse skin extracts showed that topical beta-carotene
      upregulated retinoic acid receptor-alpha and -gamma expression in the dorsal
      skin. This finding suggests that beta-carotene may work as a chemopreventive
      agent by upregulating the expression of retinoid receptors in mouse skin. In
      conclusion, our data show that beta-carotene prevents skin carcinoma formation,
      induces retinoic acid receptor expression, and fails to act as a tumor promoter
      in the two-stage model of skin tumorigenesis.

PMID- 10965525
TI  - Further evidence for chemopreventive potential of beta-carotene against
      experimental carcinogenesis: diethylnitrosamine-initiated and phenobarbital
      promoted hepatocarcinogenesis is prevented more effectively by beta-carotene than
      by retinoic acid.
AB  - The comparative effectiveness of beta-carotene (BC) and retinoic acid (RA) was
      investigated against two-stage rat liver carcinogenesis initiated by a single
      injection of diethylnitrosamine (DEN, 200 mg/kg i.p.) followed by promotion with
      phenobarbital (PB, 0.05%) in a basal diet. BC (500 mg/kg) or RA (200 mg/kg) was
      administered per os daily throughout the entire experiment, before the
      initiation, or during the promotional stage. Treatment with BC throughout the
      experiment or before initiation significantly reduced the incidence (p < 0.01),
      multiplicity (p < 0.05), and size of visible subcapsular hepatocyte nodules (HNs)
      and reduced (p < 0.001 or 0.05) nodular volume as a percentage of liver volume.
      The results with RA were of lesser extent than those observed with BC. There was
      a considerable depletion of hepatic BC and total vitamin A (retinol + ester) in
      HNs and nonnodular surrounding parenchyma (NNSP) of rats subjected to the DEN-PB
      regimen than their control counterparts. Treatment with BC significantly elevated
      hepatic BC and total vitamin A contents in HNs and NNSP compared with DEN-PB
      control, and the elevation was proportional to the duration of BC treatment. Long
      term BC or RA treatment elicited a substantial decrement in reduced glutathione
      content and gamma-glutamyltranspeptidase activity and an increment in cytochrome
      P-450 content and glutathione peroxidase and glutathione S-transferase activities
      in the HNs and NNSP, which were otherwise reversed in rats that received DEN-PB
      treatment alone. Our results suggest that BC or RA has the potential to inhibit
      DEN-induced hepatocarcinogenesis through selective modulation of the antioxidant
      defense system and xenobiotic detoxification in the liver. It is also apparent
      that the beneficial effect of BC or RA is primarily exerted on the initiation
      phase and secondarily during the promotional stage of DEN-initiated rat liver
      carcinogenesis and that BC affords a better chemopreventive response than RA.

PMID- 10965526
TI  - Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is
      associated with global DNA hypomethylation.
AB  - We measured the concentrations of folate and vitamin B-12 in paired tissue
      samples of squamous cell cancer (SCC) and adjacent grossly normal-appearing
      uninvolved bronchial mucosa (from which SCC developed and also "at risk" of
      developing SCC) of the lung in 12 subjects to determine the involvement of these
      vitamins in 1) lung carcinogenesis and 2) global DNA methylation. The folate
      concentrations were significantly lower in SCCs than in uninvolved tissues (p =
      0.03). The vitamin B-12 concentrations were also significantly lower in SCCs than
      in uninvolved tissues (p = 0.02). The radiolabeled methyl incorporation
      (inversely related to the degree of in vivo DNA methylation) was significantly
      higher in SCCs than in uninvolved tissues (p < 0.0001). The correlation between
      folate and radiolabeled methyl incorporation was inverse and statistically
      significant in SCCs (p = 0.03). The correlation between vitamin B-12 and
      radiolabeled methyl incorporation also was inverse and statistically significant
      in SCCs (p = 0.009). The relationship between tissue vitamin B-12 and DNA
      methylation was minimal in uninvolved tissues. The relationship between folate
      and DNA methylation, however, was inverse in uninvolved tissues. In the multiple
      regression models that included both vitamins, only folate was inversely
      associated with radiolabeled methyl incorporation in uninvolved and cancerous
      tissues. These results suggested that folate might be the limiting vitamin for
      proper DNA methylation in SCC as well as in tissues at risk of developing SCC.
      Several possible mechanisms of folate deficiency, including inactivation of the
      vitamin by exposure to carcinogens of cigarette smoke and underexpression or
      absence of folate receptor in SCCs and associated premalignant lesions, are
      discussed in light of these findings.

PMID- 10965527
TI  - Inverse mRNA expression of the selenocysteine-containing proteins GI-GPx and SeP
      in colorectal adenomas compared with adjacent normal mucosa.
AB  - Four selenocysteine-containing proteins (gastrointestinal glutathione peroxidase,
      plasma glutathione peroxidase, selenoprotein P, and thioredoxin reductase-alpha)
      are expressed in the colonic mucosa. Because of their antioxidant functions, a
      protective role in colon carcinogenesis is discussed. The aim of this study was
      to elucidate an involvement of gastrointestinal selenoproteins during the adenoma
      carcinoma sequence. Matched pairs of biopsies of colorectal adenomas and adjacent
      normal mucosa from 11 patients were analyzed for mRNA expression, protein
      expression, or enzyme activity of selenoproteins by Northern blot, Western blot,
      or enzymatic tests. All adenomas revealed a marked reduction of selenoprotein P
      and a variable increase of gastrointestinal glutathione peroxidase mRNA compared
      with adjacent tissue. Thioredoxin reductase-alpha and plasma glutathione
      peroxidase mRNA expression were not altered in adenomas. The Northern blot
      results were confirmed by Western blot analysis or enzyme activity measurement,
      respectively. We conclude that gastrointestinal glutathione peroxidase and
      selenoprotein P play a complementary role in the antioxidative cell defense along
      the adenoma-carcinoma sequence. It remains to be shown whether upregulation of
      gastrointestinal glutathione peroxidase in adenomas represents a compensatory
      mechanism to reduce susceptibility for oxidative damage resulting from the loss
      of selenoprotein P.

PMID- 10965528
TI  - [Danger of cellular telephones and their relay stations].
AB  - Cellular phones and their base stations emit pulsed microwaves in the
      environment. Cellular phone users are exposed in the near field and, under this
      condition, a large part of the electromagnetic energy is absorbed by the head,
      leading to an increased brain temperature. The general population is exposed
      under far field conditions to an electromagnetic intensity depending on the
      distance from the base station, passive re-emitters, the number of communications
      maintained by the base station and their position in relation to antennae (in
      front of the antenna or behind). Biological effects have been reported, such as
      radiofrequency sickness, electroencephalographic and blood pressure changes and
      also cancer risks in humans and animals exposed to microwave irradiation. Some
      European countries (Italy, France, Belgium, etc.) have taken measures to protect
      their populations.

PMID- 10965529
TI  - [Kaposi's disease and HHV8: a new model of virus-induced tumorigenesis].
AB  - Kaposi's sarcoma (KS) is a skin disease characterised by spindle cells
      proliferation and neovascularisation which, in 1994, was associated with a new
      Gammaherpesvirinae, named human herpesvirus 8 (HHV8). The HHV8 genome, containing
      more than 140 kilobases, includes genes encoding structural proteins and enzymes,
      and some homologues to cellular genes which could have been captured in host
      cells during viral evolution. Several HHV8 proteins interfere with the host
      cellular cycle either by inhibiting apoptosis or by positive regulation of the
      cell cycle (viral cyclin or v-cyclin, v-bcl-2, v-FLIP). HHV8 also contains
      potential oncogenes (v-IRF and v-GPCR, which promote angiogenesis, in particular
      the secretion of VEGF) as well as homologues of human cytokines and chemokines (v
      IL6, v-MIP). HHV8 is clearly associated with KS, multicentric Castleman disease
      and primary effusion lymphoma. Most of the cells are infected by latent virus,
      resulting in persistent infection of the lesions. Only a minority of infected
      cells yield infectious viral particles, and their role in the development of KS
      and other associated diseases has not been clearly established. The molecular
      mechanisms and cofactors involved in the physiopathology of this infection have
      yet to be identified.

PMID- 10965530
TI  - [Muco-cutaneous colonization and nosocomial infections caused by methicillin
      resistant Staphylococcus aureus and Acinetobacter baumanii in intensive care
      patients].
AB  - This study was designed to assess the frequency and risk factors for colonization
      with MRSA and A. baumanii in the intensive care unit, and to analyse the
      relationship between colonization and infection with MRSA or A. baumanii. During
      a 24-day survey period, colonization was studied weekly with nasal, throat and
      digit skin swabs; nosocomial infections were routinely monitored according to CDC
      recommendations. Clinical data and invasive procedures were registered during a
      one-year non-epidemic period; 103 ICU patients hospitalized for more than 7 days
      were prospectively included. We investigated acquired colonization and nosocomial
      infection with SAMR or A. baumanii for 87 patients not colonized by SAMR or A.
      baumanii on admission. The colonization acquisition rate was 56% for MRSA and 27%
      for A. baumanii. Infection incidence (cases per 1,000 patient-days) was 6.46 for
      MRSA and 1.61 for A. baumanii. On univariate analysis, acquired MRSA colonization
      was associated with longer ICU stays, longer mechanical ventilation and longer
      central venous catheterization. Multivariate analysis only showed an association
      with longer ICU stay. Acquired A. baumanii colonization was associated with
      SAPSII, longer mechanical ventilation, and longer central venous catheterization
      in univariate analysis. Multivariate analysis only showed an association with
      SAPSII and longer mechanical ventilation. In this study, SAMR or A. baumanii
      infections were not associated with colonization or clinical setting or invasive
      procedures.

PMID- 10965531
TI  - [Genotyping of Toxoplasma gondii strains from immunocompromised patients].
AB  - The genotypes of Toxoplasma gondii strains isolated from HIV and non-HIV
      immunocompromised patients with cerebral and extracerebral toxoplasmosis were
      determined and compared to those of strains isolated from non-immunocompromised
      patients in order to identify the possible relationships between parasite
      genotype and morbidity of toxoplasmosis. One hundred and ten strains of T. gondii
      were obtained, either by cell culture (n = 73), brain biopsy (n = 17) or mouse
      inoculation (n = 20). Ninety strains isolated from immunocompromised patients (74
      HIV+ and 16 non-HIV patients) were compared to 20 strains isolated from
      immunocompetent patients (17 cases of congenital toxoplasmosis, and three cases
      of primary acquired infection). Genotyping was performed by PCR/RFLP on locus
      SAG2, and T. gondii strains were classified as Type I, II or III. Ninety out of
      110 strains were successfully genotyped, including 20 strains that had been
      maintained in mice, 69/73 strains maintained in cell cultures, but only 1/17
      strains from formalin-fixed paraffin-embedded brain biopsies. 76.7% of the
      strains in the study population were of type II, 15.6% were type I and 7.7% were
      type III. The distribution of strain genotypes in immunocompromised and non
      immunocompromised patients was comparable: 14.1% and 21% for type I, 76.1% and
      79% for type II and 9.8% and 0% for type III, respectively; no correlation could
      be established between genotype and clinical presentation, i.e., cerebral or
      extracerebral toxoplasmosis. These results suggest that the type of infecting
      parasitic strain does not predominantly influence the pathogenesis of
      toxoplasmosis in immunocompromised patients and fully supports the need for
      specific prophylaxis in patients infected by T. gondii, regardless of the strain
      genotype.

PMID- 10965532
TI  - Detection of benzo[a]pyrene-DNA adducts in leukocytes of coke oven workers.
AB  - Coke oven workers are often heavily exposed to polynuclear aromatic hydrocarbons
      (PAHs) and particularly to benzo[a]pyrene (B[a]P), which has been associated with
      a high incidence of cancer. B[a]P is metabolically activated to its diol-epoxide
      derivative, benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE-I), a potent
      carcinogen which binds covalently to DNA, thereby producing BPDE-I-DNA adducts.
      In this study, an investigation was made of the exposure of coke oven workers to
      PAH via the measurement of urinary 1-hydroxypyrene (1-OHP) levels, and of
      exposure to B[a]P by the analysis of BPDE-I-DNA adducts in leukocytes using an
      ELISA competitive immunoassay. 1-OHP levels measured in post-shift samples
      correlated with those of DNA adducts detected in leukocytes, with a mean value
      (140.11 fM/50 micrograms of DNA) which differed significantly from the control
      value (P < 0.001). It is concluded that measurement of BPDE-I-DNA adduct levels
      in coke plant workers is essential in determining cancer risk due to high
      exposure to PAHs, and in particular of B[a]P.

PMID- 10965533
TI  - Urinary creatinine excretion in children from families with Balkan endemic
      nephropathy: evidence for genetic predisposition to the disease.
AB  - Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease
      prevalent in Serbia, Bosnia, Croatia, Bulgaria and Romania. Genetic studies have
      supported the genetic predisposition to BEN, and some studies in Bulgaria and in
      the Kolubara region of Serbia have revealed abnormalities of the urinary tract in
      up to 46% of children from families with BEN. In the present study, urinary
      excretion of creatinine, an index of muscle mass, was studied in 703 healthy
      children from endemic and non-endemic areas around the South Morava River. The
      survey covered a three-year period, and the children were studied three times a
      year: in the spring, autumn and winter. A urine sample for the period
      corresponding to 7-10 a.m. was collected during each study period. Evidence has
      been presented that children from families with BEN excrete significantly less
      creatinine than those from families without BEN living in the same area, or than
      children living in villages outside the endemic region or in the city of Nis.
      This study supports the view that genetic predisposition to BEN is indicated by a
      smaller muscle mass, although the effect of living conditions and nutrition may
      also contribute to this.

PMID- 10965534
TI  - Balkan endemic nephropathy: a decreasing incidence of the disease.
AB  - Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease
      prevalent in Serbia, Bosnia, Croatia, Bulgaria and Romania. This study
      investigates the incidence of BEN patients on dialysis with end-stage kidney
      disease (ESKD), and BEN-associated mortality in endemic areas around the South
      Morava River in Serbia from 1978 to 1997. In the last 10 years a marked decrease
      in the incidence of ESRD and BEN-induced mortality has been documented in the
      region. This study shows a significantly decreased incidence of BEN in endemic
      areas in South Serbia. Since the effects of etiological agent(s) on renal
      function in children from families in endemic areas was demonstrated in the early
      nineties and the disease seems to have an endemic-epidemic profile, the
      possibility of another epidemic outbreak in the future cannot be excluded.

PMID- 10965535
TI  - NA antigen frequencies in the Tunisian population.
AB  - The biallelic NA antigen system is of special interest as the NA antigens are
      frequent targets of neutrophil antibodies, causing alloimmune neonatal
      neutropenia, blood transfusion reactions, and chronic benign autoimmune
      neutropenia in infancy. Neutrophils isolated from the peripheral blood of 119
      unrelated individuals at the National Blood Center were phenotyped for NA1 and
      NA2 using a granulocyte immunofluorescence assay. A subsequent analysis of the
      phenotyping study showed that the NA1 and NA2 antigen frequencies were 0.529 and
      0.865 respectively, and that the estimated NA1 and NA2 gene frequencies were
      0.313 and 0.632 respectively. In conclusion, it was determined that the Tunisian
      population is of Caucasian origin. However, to validate this finding, further
      investigations are necessary.

PMID- 10965536
TI  - [Eosinophil apoptosis in asthma].
AB  - Eosinophils play a major role in the onset and maintenance of bronchial
      inflammation and tissue injury in asthma. Like other leukocytes, eosinophils
      present in excessive numbers in inflamed tissues are removed by apoptosis. This
      phenomenon, also called 'programmed cell death', allows elimination of dangerous
      or redundant cells, thereby ensuring maintenance of tissue homeostasis. It has
      been suggested that a defect in eosinophil apoptosis would participate in the
      development and persistence of allergic airways inflammation in asthma.
      Eosinophil apoptosis, as well as the expression and function of various molecules
      determining this process, are closely regulated by various stimuli, including
      cytokines, lipid mediators and growth factors released by various cell types and
      by the eosinophil itself, as well as exogenous molecules, such as
      glucocorticoids. These stimuli have been shown to alter the expression and
      function of different molecules involved in the cascade of events characterising
      the apoptotic process, particularly Bcl-2 family proteins and the pro-apoptotic
      membrane glycoprotein, Fas. These observations, together with a better
      understanding of the mechanisms underlying eosinophil apoptosis, will help to
      more clearly define the molecular events involved in accumulation of these cells
      in blood and tissues and to identify potential new targets for the treatment of
      allergic diseases.

PMID- 10965537
TI  - CD5-positive B cells at the crossroads of B cell malignancy and nonorgan-specific
      autoimmunity.
AB  - The CD5 glycoprotein is detectable on a minute fraction of circulating B cells.
      The number of CD5+ B cells (B1 cells) is increased in patients with autoimmune
      disorders and these cells, similar to those leading to chronic lymphocytic
      leukemia (CLL), may be induced to produce multispecific autoantibodies. CD5 is
      associated with the B cell antigen receptor, and the induction of apoptosis
      depends on the activation state of the cells. Defective regulation of this
      phenomenon might result in the production of autoantibodies and/or the
      development of CD5+ B cell tumors. We have proposed that there may be different
      B1 populations in man, which depend on the consequence of CD5 ligation on their
      surface: 'natural' or 'classical' CD5+ B cells, and 'induced' CD5+ B cells.

PMID- 10965538
TI  - [Cellular and molecular features of mammalian pigmentation--tyrosinase and TRP].
AB  - Melanin pigments are found in all biological kingdoms. At the cellular level,
      correct pigmentation depends not only on correct migration of pigment cells
      (melanocytes) and their precursors (melanoblasts), but also on specialized
      cytoplasmic organelles, melanosomes. Three pigment cell-specific enzymes inside
      melanosomes are involved in melanogenesis: tyrosinase, TRP-1 and TRP-2/DOPA
      chrome tautomerase. A point mutation of tyrosinase is sufficient to give rise to
      a nonfunctional enzyme, leading to albinism and associated decreased visual
      acuity. Several regulatory elements have been identified within the promoters of
      the genes encoding these three enzymes. These promoter fragments have been used
      to target the expression of heterogeneous genes in pigment cells of transgenic
      mice.

PMID- 10965539
TI  - Psychiatry: introduction to the study of interpersonal relations. Chapter I. The
      data of psychiatry. 1938.

PMID- 10965540
TI  - Seeing Sullivan as part of 20th century developments.

PMID- 10965541
TI  - The silent assimilation of the interpersonal perspective.

PMID- 10965542
TI  - Interpersonal pathways to health.

PMID- 10965543
TI  - Somatic symptoms in children and adolescents referred for emotional and
      behavioral disorders.
AB  - Medically unexplained physical symptoms are frequently endorsed by children and
      adolescents in both clinical and community samples. The aim of this exploratory
      study is to examine the prevalence of somatic symptoms in a sample of 162 Italian
      children and adolescents consecutively referred to a Division of Child Neurology
      and Psychiatry from emotional and/or behavioral disorders. The role of age,
      gender, and psychiatric status was considered as a variable. Each patient
      received a DSM-IV assessment, including a diagnostic structured interview (DICA
      R). The sample was divided according to gender (96 males, 66 females), age (70
      children younger and 92 adolescents older than 12 years), and psychiatric
      diagnosis (Anxiety, Depression, Depression/Anxiety, Other). The presence of
      medically unexplained somatic symptoms was based on the responses to the DICA-R.
      Somatic complaints were reported in 69.2% of the patients. Headache was the most
      frequent somatic symptom (50.6%). Younger children showed higher rates of
      abdominal complaints than adolescents. No gender differences in frequency of
      somatic complaints were reported. Subjects with anxiety and/or depression
      reported significantly higher rates of somatic complaints, namely headache, than
      subjects with other mental disorders. No differences in frequency of somatic
      symptoms were evident between patients with anxiety, depression, and comorbid
      anxiety-depression. Our data suggest that an unexplained somatic symptom can be
      often considered as indicative of a neglected anxiety and/or depressive disorder.
      A collaboration between primary care physicians, pediatricians, and child
      psychiatrists may promote early diagnoses and timely treatments and prevent
      negative social and scholastic consequences.

PMID- 10965544
TI  - Children are not miniature adults.

PMID- 10965545
TI  - Unexplained physical symptoms: medicine's "dirty little secret" and the need for
      prospective studies that start in childhood.

PMID- 10965547
TI  - Lessons from advance directives for PADs.

PMID- 10965546
TI  - Psychiatric advance directives: an alternative to coercive treatment?
AB  - Psychiatric Advance Directives (PADs) are a legal means by which persons with
      mental illness, while competent to make healthcare decisions, may specify their
      preferences for treatment and may designate a surrogate decision-maker to act on
      their behalf in the event of an incapacitating mental health crisis. PADs have
      been advocated as a strategy to increase autonomy and decrease coercion in the
      treatment of severe psychiatric illness, but there has been little research on
      the actual use and effects of PADs. This article develops a conceptual model for
      how PADs might work, both directly and indirectly. According to the model
      proposed here, PADs might provide an effective tool for managing psychiatric
      crises but might also help to improve participation in regular outpatient
      treatment. This article further examines arguments for and against PADs and looks
      optimistically toward their use as an alternative to more coercive approaches to
      mental health treatment such as outpatient commitment (OPC).

PMID- 10965548
TI  - Have dual survival systems created the human mind?
AB  - This article reviews pertinent psychological theory to argue for two discrete
      human motivational tracts. These dual systems appear to draw from disparate
      constellations of emotional energies that normatively become interactive across
      development. The article stipulates eight premises from the accepted tenets of
      psychology, development, and pathology along with corroborating evidence from
      laterality studies, neuropsychology, and the neurosciences. These premises lead
      to a verifiable hypothesis reflecting Richard Leakey's proposal that H. sapiens
      emerged from an interpersonal shaping of adaptation across several million years
      of group living. The totality of the supportive evidence suggests that the
      flexibility, agility, and creativity of the human mind was abetted by tensions
      and reconciliations between two disparate hemispheric perspectives, which express
      as a Personal Self and a Social Self, focused by a lens molded by survival
      pressures.

PMID- 10965549
TI  - Abducted by aliens: a case study.
AB  - This article describes a case of Shared Psychotic Disorder in a married couple.
      Because only one of the partners of the pair (the inducer) was alive, at the time
      of the research, the other partner (the recipient) is presented by using a
      "psychological autopsy" based both on 19 tape recordings containing her
      delusional recollections and on a history provided by the husband. The content of
      their delusion, shaped by a fantasy theme of contemporary Western culture, is
      unique among cases of Shared Psychotic Disorder published in the last 30 years.
      The discussion following the case presentation draws attention to the potential
      risk of this type of case leading to a homicide-suicide pact. Additionally,
      comments are made about both the pathogenesis, with emphasis on psychodynamic
      hypothesis, and a consideration of the prognosis, which seems modulated by
      cultural factors.

PMID- 10965550
TI  - A disturbed child's use of a public event: Cotard's syndrome in a ten-year-old.
AB  - Public events can be incorporated into the mental life and life narratives of
      children with psychiatric illnesses. A 10-year-old boy who was not in Oklahoma
      City at the time of the 1995 bombing of the Murrah Federal Building and who knew
      no one directly impacted, claimed that he himself was dead, then that his
      grandfather, and finally that a peer and the peer's family had been killed in the
      blast. This is the first known reported case of Cotard's syndrome, the delusion
      of being dead, in a prepubescent child. The article also explores the
      relationships between this boy's symptoms, transference phenomena, real life
      events, themes of loss, abandonment, neglect, and death, and his fabricated
      stories.

PMID- 10965551
TI  - Effect of hepatitis C virus on hepatocyte proliferation and DNA ploidy in
      patients with chronic hepatitis C.
AB  - Hepatitis C virus infection may act as a cofactor by inducing chronic hepatitis
      and cirrhosis, playing a promoting role in the multistep process of
      hepatocarcinogenesis by maintaining liver inflammation, hepatocyte necrosis and
      regeneration. The aim of this study was to measure the DNA ploidy and cell
      proliferation of hepatocytes in patients with chronic hepatitis C. Hepatocyte
      nucleus suspension was analyzed from 45 patients with chronic hepatitis C and
      from 27 patients with chronic hepatitis non-C. The histopathological pattern of
      chronic hepatitis samples/grade, stage/was investigated. A significantly lower
      cyclin A protein expression and cytometrically measured S-phase fraction was
      observed in chronic hepatitis C as compared to chronic hepatitis non-C,
      representing suppressed cell proliferation of virus infected cells. In the
      chronic hepatitis C groups, the S-phase fraction depression was moderate, the
      grade of inflammation and cyclin A protein expression were also decreased, mainly
      in the severe grade group. In chronic hepatitis non-C, the number of cyclin A
      staining-positive cells increased parallel with severity of the inflammation. In
      addition, the HCV infection caused a near diploid minimally aneuploid cellular
      DNA content in the cases of moderate and severe histological groups. In contrast,
      the cellular DNA content was consequently diploid-independent of histological
      grades in chronic hepatitis non-C. Our results suggest that in chronic viral
      hepatitis C, the hepatocyte proliferation is suppressed parallel with the degree
      of inflammation, while the DNA content becomes aneuploid. The aneuploidy is a
      sign of genetic instability, predisposing the affected cells to unbalanced
      chromosomal abnormality which finally leads to malignant transformation.

PMID- 10965552
TI  - Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori
      positive patients.
AB  - BACKGROUND: Only 10-15% of all patients infected with Helicobacter pylori develop
      peptic ulcer disease (PUD) or gastric cancer. Apart from immunological factors in
      the host, virulence determinants of H. pylori such as the vacuolating cytotoxin
      (VacA) or the cytotoxin-associated protein A (CagA) might represent a
      predisposition for the development of PUD. METHODS: We studied antral biopsies of
      383 H. pylori-positive patients with peptic ulcer disease (PUD) or other H.
      pylori-related diseases for H. pylori vacA genotypes and the presence of the cagA
      gene by PCR. RESULTS: VacA genotypes and cagA status could be completely
      determined in 357 (93.2%) of the patients. In 91 (93.8%) of 97 patients with PUD,
      the vacA s1 genotype (s1m1, 45; s1m2, 46 patients) was present. The vacA s2m2
      genotype was found in only 6 (6.2%) of 97 patients with PUD. In contrast, 180
      (75.3%) of 239 patients (s1m1, 89; s1m2, 91 patients) without PUD and without
      gastric malignancies harbored strains with the vacA s1 genotype. The vacA
      genotype s2m2 was found in 59 (24.7%) of these patients. The presence of the cagA
      gene was closely associated with the vacA genotype s1 and found in 124 (88.6%)
      and in 113 (80.7%) of patients with the s1m1 or s1m2 genotypes, respectively,
      whereas strains with the genotype s2m2 were almost exclusively cagA negative.
      CONCLUSION: Most H. pylori strains found in patients with PUD possess the vacA s1
      genotype and the cagA gene. Patients with this type of H. pylori strain but
      without PUD might be at higher risk of developing PUD. In contrast, the risk for
      PUD might be significantly decreased in those patients who are infected by H.
      pylori strains with the vacA s2 genotype lacking the cagA gene.

PMID- 10965555
TI  - Isolated massive pleural effusion caused by pancreatico-pleural fistula.
AB  - BACKGROUND: Massive pleural effusions are uncommon but well-documented
      complications of chronic pancreatitis, usually caused by the development of a
      pancreaticopleural fistula. The mechanism of the fistula formation is thought to
      be rupture of the pancreatic duct or pseudocyst. MATERIAL AND METHODS: In the
      past 7 years we have treated 5 patients with massive pleural effusion of
      pancreatic origin in the Surgical Department of Semmelweis University Medical
      School. 4 patients were males; the average age was 52 years (range: 46-59 years).
      RESULTS: All 5 patients had a history of alcohol abuse and were admitted to the
      pulmonary department because of respiratory distress. Other symptoms such as
      abdominal pain, chest pain, or weight loss were not always present. The diagnosis
      was confirmed by a markedly elevated amylase level in the aspirated pleural
      fluid. Abdominal ultrasound, CT scan, and ERCP examinations were carried out in
      order to determine the cause of the pancreaticopleural fistula. Conservative
      (nonsurgical) treatment was effective within 3 weeks in only one case. The other
      4 patients required surgical management. In 3 cases distal pancreatic resection
      with splenectomy and cholecystectomy was done. In one case cystojejunostomy was
      performed. All 5 patients have been cured with complete resolution of their
      pleural effusions. CONCLUSIONS: Patients with large pleural effusions may have
      underlying pancreatitis with a pancreaticopleural fistula. It is important to
      establish this diagnosis because treatment may require operative interventions.

PMID- 10965553
TI  - Bile and acid reflux in long and short segment Barrett's esophagus, and in reflux
      disease.
AB  - Gastroesophageal acid reflux (GER) is the primary risk factor for
      gastroesophageal reflux disease (GERD). In long segment Barrett's esophagus
      (LSBE) duodenogastroesophageal reflux (DGER) parallels acid reflux. The role of
      GER and DGER in short segment Barrett's esophagus (SSBE) remains to be
      determined. The aim of the present prospective study was to investigate the
      esophageal bile and acid reflux in patients with LSBE, SSBE and patients with
      GERD. Three groups of patients were studied: Patients with LSBE (n = 12), SSBE (n
      = 20) and patients with GERD without intestinal metaplasia (n = 33). Subjects
      underwent esophageal manometry and simultaneous 24-h pH and bile monitoring
      (Bilitec 2000). The thresholds for GER and DGER were a deMeester score > 14.7 and
      an absorbance value > 0.2 for 10.9% of total period, respectively. GER did not
      differ between the groups (p > 0.05). However, DGER differed between patients
      with LSBE, SSBE and GERD (14.7 vs 2.1 vs 2.1, respectively; p < 0.05). H. pylori
      status did not influence GER and DGER significantly. In contrast to patients with
      LSBE the DGER does not seem to play an important role in patients with SSBE and
      patients with GERD. This result indicates a different etiopathology of both long
      and short segment Barrett's esophagus.

PMID- 10965554
TI  - [The therapy of acute pancreatitis. General guidelines. Working group of the
      Society for Scientific-Medical Specialties].

PMID- 10965556
TI  - [Cholestatic hepatitis as a rare side effect of therapy with ticlopidine].
AB  - A 71-year-old man with chronic atrial fibrillation was treated with aspirin
      because of a right cerebral infarction. Oral anticoagulation was not initiated
      because of a secondary hemorrhagic transformation. Six years later after a left
      cerebral transient ischemic attack aspirin was replaced by ticlopidine. Two weeks
      after starting ticlopidine he experienced abdominal cramps and diarrhea. Also
      dark urine and gray-colored stools were noticed, so that the patient stopped
      taking ticlopidine. 40 days after starting ticlopidine he was admitted to our
      hospital because of cholestatic jaundice. Serum alkaline phosphatase (305 U/l)
      and gamma GT (143 U/l) were elevated, the total bilirubin was 18.6 mg/dl at peak.
      GOT and GPT were 2.7 fold increased. After exclusion of a viral infection and
      autoimmune disease liver biopsy was performed, which showed a centroacinar
      cholestasis compatible with a drug-induced liver damage. 79 days after
      discontinuation of the drug laboratory signs of cholestasis had disappeared. In
      patients in whom long-term therapy with ticlopidine is indicated regularly
      laboratory tests and clinical examinations should be done to recognize infrequent
      side effects such as the cholestatic hepatitis in time.

PMID- 10965558
TI  - [Diagnostic and therapeutic enteroscopy. Its current status].
AB  - In many gastroenterological departments, the push-enteroscopy has become a well
      established method to investigate the small bowel. Compared to the sonde
      enteroscopy, this method has the advantage of offering the opportunity to
      intervene (e.g., taking biopsies, polypectomy, electrocoagulation) since the push
      enteroscope has a working channel. The main indication for an endoscopic
      procedure is still the search for intestinal sources of bleeding after more
      frequent sources in the gastrointestinal tract have been ruled out. Other
      diagnostic and therapeutic indications are less frequent. In this overview we
      will first describe the procedure. Then we will review the most recent diagnostic
      and therapeutic aspects of the push-enteroscopy and compare it to other
      procedures.

PMID- 10965557
TI  - [A 42-year-old patient with the hemolytic-uremic syndrome under gemcitabine
      therapy for an adenocarcinoma of the liver. The hemolytic-uremic syndrome and
      gemcitabine].
AB  - We report on the case of a 42-year-old man suffering from an irresectable
      adenocarcinoma of the liver. The patient was treated with 5-fluorouracil for 6
      months when the disease progressed and second line therapy with gemcitabine was
      started. After 4 months diastolic blood pressure increased and edema of the legs
      as well as vomiting occurred. Laboratory tests revealed anemia and thrombopenia
      accompanied by an elevation of plasma D-dimer, lactatdehydrogenase, creatinine,
      and urea levels in the serum. In addition, a pronounced proteinuria as well as
      renal hematuria were detected and subsequently a hemolytic uremic syndrome was
      diagnosed. After treatment with high-dose glucocorticoids, anticoagulants and
      transfusions of packed RBC the course of disease improved. Since Gemcitabine is
      now widely used for treatment of solid organ cancer (e.g. pancreatic
      adenocarcinoma, biliary tract cancer, lung cancer etc.), it is necessary to be
      aware of Gemcitabine-induced hemolytic uremic syndrome as a rare but potentially
      fatal side effect.

PMID- 10965559
TI  - [The natural history of pain in alcoholic chronic pancreatitis].

PMID- 10965560
TI  - [Germline mutations of the MSH6 gene in patients with an atypical hereditary
      nonpolyposis colorectal carcinoma (HNPCC)].

PMID- 10965561
TI  - [Thrombin--a new therapeutic option for arresting hemorrhages from gastric
      varices?].

PMID- 10965562
TI  - Longevity of breeding sows in relation to leg weakness symptoms at six months of
      age.
AB  - The objective of this study was to evaluate the influence of leg weakness
      symptoms measured early in life (at 6 months of age) on the longevity of the
      sows, i.e. the age at culling due to locomotory problems in a Danish pig herd.
      One hundred and eighty-seven gilts at 6 months of age were selected according to
      different leg weakness symptoms and were followed until culling and judged for
      leg weakness once in every gestation using a scale from 1 (normal) to 4 (severe
      changes). Age at culling, and the main and secondary reasons for culling were
      recorded. The influence of leg weakness symptoms on longevity was evaluated by
      survival analysis. Though only 12% of the gilts showed a stiff locomotion half of
      the sows had suffered from this and nearly one third had been distinctly lame at
      some time in their life. Buck-kneed forelegs, upright pasterns, legs turned out,
      standing under position and swaying hindquarters were associated with stiff
      locomotion or lameness, whereas weak pasterns on hind legs and splayed digits on
      forelegs were associated with brisk movement (freedom from locomotor problems).
      The following leg weakness symptoms at the gilt stage were found to have
      significant negative effects on longevity: buck-kneed forelegs, swaying
      hindquarters, and standing under position on hind legs.

PMID- 10965563
TI  - Osteochondrosis/osteoarthrosis and claw disorders in sows, associated with leg
      weakness.
AB  - The objective of this study was to investigate the associations between different
      leg weakness symptoms and osteochondrosis/osteoarthrosis and claw disorders in
      sows together with the influence of age on these findings. One hundred and
      seventeen sows in one herd were followed from 6 months of age until culling and
      judged for leg weakness once in every gestation using a scale from 1 (normal) to
      4 (severe changes). At slaughter changes in joints, growth plates and claws were
      scored on a scale from 1 (normal) to 5 (very severe changes). Osteoarthrotic
      changes were strongly associated with osteochondral changes in humeral and
      femoral condyles. The clinical signs of osteochondrosis and osteoarthrosis were
      found to be: buck-kneed forelegs, turn out of fore and hind legs, upright
      pasterns on hind legs, stiff locomotion, lameness and tendency to slip. The
      clinical signs of claw lesions were found to be: buck-kneed forelegs, upright
      pasterns, steep hock joints, turn out of hind legs, standing under position on
      hind legs, stiff movements, swaying hindquarters, goose-stepping hind legs,
      tendency to slip and lameness. Overgrown claws were strongly associated with leg
      weakness indicating the need for claw trimming in sow populations.

PMID- 10965564
TI  - Increasing prevalence of Mycoplasma bovis in Danish cattle.
AB  - A study on the prevalence of mycoplasmas in pneumonic bovine lungs was performed
      on material submitted for diagnostic purposes at the Danish Veterinary
      Laboratory, Copenhagen. Among the 50 examined cases 43 (86.0%) were found to be
      infected with mycoplasmas. The predominant mycoplasmas were Ureaplasma spp.
      (72.0%), M. dispar (48.0%) and M. bovis (24.0%). Other mycoplasmas were M.
      bovirhinis (20.0%) and M. bovigenitalium (6.0%). Among the infected lungs
      multiple species infections were predominant (76.7%) over single species
      infections (23.3%) with M. dispar-Ureaplasma (25.6%), M. bovis-Ureaplasma (18.6%)
      and M. dispar-M. bovirhinis-Ureaplasma (11.6%) infections being the most
      frequently encountered combinations. There appears to be an increasing prevalence
      of M. bovis (24.0%) as compared to earlier reports (0.6-2.0%), thus calling for
      special attention upon this mycoplasma. Pulsed field gel electrophoresis (PFGE)
      analysis of 11 field isolates of M. bovis from 9 different farms revealed
      different profiles except for 2 isolates which were recovered from the same farm.
      Because mycoplasmas belonging to the 'M. mycoides cluster' were not encountered
      during this study; it appears that the Danish cattle population is still free
      from this group of mycoplasma in spite of their presence in some other European
      countries.

PMID- 10965565
TI  - Absence of obvious short-term impact of the nematode-trapping fungus Duddingtonia
      flagrans on survival and growth of the earthworm Aporrectodea longa.
AB  - The nematode-trapping fungus Duddingtonia flagrans may be used in biological
      control of parasitic nematode larvae in faeces of domestic host animals after
      feeding the hosts with fungal chlamydospores. In this experiment a possible
      undesirable fungal impact on earthworms, of the species Aporrectodea longa, was
      investigated. As earthworms eat animal faeces, D. flagrans may come into contact
      with earthworms both in their alimentary tract and on their body surface. However
      during the experimental period of 20 days, when earthworms were living in soil
      and eating cattle faeces that were heavily infested with viable chlamydospores of
      D. flagrans there were no indications of internal or external mycosis among the
      earthworms.

PMID- 10965566
TI  - Nose-rings and transmission of helminth parasites in outdoor pigs.
AB  - Five growing pigs experimentally infected with low doses of Oesophagostomum
      dentatum, Ascaris suum, and Trichuris suis were turned out with 5 helminth-naive
      pigs on each of 3 pastures in June 1996 (Group 1). On one pasture all pigs
      received nose-rings. After slaughter of Group 1 in October, pasture infectivity
      was monitored using helminth-naive, unringed tracer pigs. In 1997, helminth-naive
      young pigs were turned out on the contaminated pastures in May (Group 2) and
      again in August (Group 3). Again all pigs on one pasture received nose-rings. All
      pigs and pastures were followed parasitologically and reduction in grass cover
      was monitored. Based on the acquisition of infection by the naive pigs in Group
      1, the estimated minimal embryonation times for eggs deposited on pasture were 23
      25 days for O. dentatum, 5-6 weeks for A. suum and 9-10 weeks for T. suis.
      Results from tracer pigs and grass/soil samples indicated that pasture
      infectivity was light both years. Free-living stages of O. dentatum did not
      survive the winter. The nose-rings reduced rooting considerably, resulting in
      three-fold more grass cover on the nose-ring pasture compared to the control
      pastures by the end of the experiment. Nevertheless, the nose-rings did not
      significantly influence parasite transmission.

PMID- 10965567
TI  - Listeria monocytogenes in faeces from clinically healthy dairy cows in Sweden.
AB  - Faecal samples from 102 clinically healthy dairy cows, representing 34 farms in
      the Swedish province of Uppsala, were analysed for the presence of Listeria spp.
      using an enrichment procedure. Listeria monocytogenes was isolated from six (6%)
      and L. innocua from 2 (2%) cows. From each of the 6 samples positive for L.
      monocytogenes, 5 isolates were further characterised by restriction enzyme
      analysis using the 3 enzymes Apa I, Sma I, and Asc I, followed by pulsed-field
      gel electrophoresis. Three of the L. monocytogenes positive cows lived at the
      same farm, and they all harboured the same clonal type. One of these 3 cows also
      harboured a further clonal type of L. monocytogenes. The fact that one of the
      cows harboured 2 different clonal types of L. monocytogenes is important from an
      epidemiological point of view when routes of infection are to be investigated.

PMID- 10965568
TI  - Physiological and endocrinological responses during prolonged exercise in
      hatchery-reared rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) were subjected to vigorous exercise (1.5 body
      length s-1), low exercise (0.5 body length s-1) or still-water (0.0 body length s
      1). Hematocrit, glucose, growth hormone (GH), cortisol and triiodo-L-thyronine
      (T3) were monitored at the start of exercise, after 24 h, and after 2, 4, 8, 16
      and 32 days of continuous swimming. Morphological indices and food intake were
      also monitored. At the end of the experiment, trout subjected to low exercise had
      gained significantly (p < 0.05) more weight than both the control (still-water)
      and vigorously exercised fish. This low exercised group of fish also consumed
      more food than the 2 other groups. Hematocrit increased significantly in both
      exercised groups at the onset of swimming but returned to pre-exercise levels
      within 8 hrs. Plasma glucose appeared to be generally unaffected by exercise.
      Likewise, plasma concentrations of both GH and T3 were not influenced by
      exercise. Plasma cortisol levels increased in an exercise dependent fashion at
      the onset of swimming, but returned to pre-swimming levels within 24 h and there
      was no apparent effect of sustained swimming. The results suggest: (i) the onset
      of exercise elicits transient changes in plasma components, (ii) the observed
      weight gain in low exercising salmonids occur without increases in circulating
      levels of GH or T3.

PMID- 10965570
TI  - Optimizing breeding decisions for Finnish dairy herds.
AB  - The purpose of this study was to determine the effect of reproductive performance
      on profitability and optimal breeding decisions for Finnish dairy herds. We used
      a dynamic programming model to optimize dairy cow insemination and replacement
      decisions. This optimization model maximizes the expected net revenues from a
      given cow and her replacements over a decision horizon. Input values and prices
      reflecting the situation in 1998 in Finland were used in the study. Reproductive
      performance was reflected in the model by overall pregnancy rate, which was a
      function of heat detection and conception rate. Seasonality was included in
      conception rate. The base run had a pregnancy rate of 0.49 (both heat detection
      and conception rate of 0.7). Different scenarios were modeled by changing levels
      of conception rate, heat detection, and seasonality in fertility. Reproductive
      performance had a considerable impact on profitability of a herd; good heat
      detection and conception rates provided an opportunity for management control.
      When heat detection rate decreased from 0.7 to 0.5, and everything else was held
      constant, net revenues decreased approximately 2.6%. If the conception rate also
      decreased to 0.5 (resulting in a pregnancy rate of 0.25), net revenues were
      approximately 5% lower than with a pregnancy rate of 0.49. With lower fertility,
      replacement percentage was higher and the financial losses were mainly from
      higher replacement costs. Under Finnish conditions, it is not optimal to start
      breeding cows calving in spring and early summer immediately after the voluntary
      waiting period. Instead, it is preferable to allow the calving interval to
      lengthen for these cows so that their next calving is in the fall. However, cows
      calving in the fall should be bred immediately after the voluntary waiting
      period. Across all scenarios, optimal solutions predicted most calvings should
      occur in fall and the most profitable time to bring a replacement heifer into a
      herd was in the fall. It was economically justifiable to keep breeding high
      producing cows longer than low producing cows.

PMID- 10965569
TI  - Optimizing replacement decisions for Finnish dairy herds.
AB  - The purposes of the study were to determine how "an optimal herd" would be
      structured with respect to its calving pattern, average herdlife and calving
      interval, and to evaluate how sensitive the optimal solution was to changes in
      input prices, which reflected the situation in Finland in 1998. The study used
      Finnish input values in an optimization model developed for dairy cow
      insemination and replacement decisions. The objective of the optimization model
      was to maximize the expected net present value from present and replacement cows
      over a given decision horizon. In the optimal solution, the average net revenues
      per cow were highest in December and lowest in July, due to seasonal milk
      pricing. Based on the expected net present value of a replacement heifer over the
      decision horizon, calving in September was optimal. In the optimal solution, an
      average calving interval was 363 days and average herdlife after first calving
      was 48.2 months (i.e., approximately 4 complete lactations). However, there was a
      marked seasonal variation in the length of a calving interval (it being longest
      in spring and early summer) that can be explained by the goal of having more cows
      calving in the fall. This, in turn, was due to seasonal milk pricing and higher
      production in the fall. In the optimal solution, total replacement percentage was
      26, with the highest frequency of voluntary culling occurring at the end of the
      year. Seasonal patterns in calving and replacement frequencies by calendar month
      and variation in calving interval length or herdlife did not change meaningfully
      (< 1%-2% change in the output variables) with changes in calf, carcass or feed
      prices. When the price of a replacement heifer decreased, average herdlife was
      shorter and replacement percentage increased. When the price increased, the
      effect was the opposite.

PMID- 10965571
TI  - [Pyeloureteral junction stenosis: our experience and review of the literature].
AB  - OBJECTIVES: To study patients with ureteropelvic junction obstruction treated in
      our department and a retrospective study of this pathology, focus our attention
      in the diagnosis and treatment. MATERIAL AND METHODS: 62 patients from 7 weeks to
      68 years old (mean 29 +/- 1.9). Half of the patients were men and the other half
      women. In 30 patients the UPJ obstruction was on the right side and 32 patients
      was on the left side. RESULTS: The most frequent symptom was the flank pain
      (46.8%). To confirm the diagnosis, we had IVU in the 61.3% of the patients and
      ultrasound in the 38.7%. The treatment was the Anderson-Hynes pyeloplasty in the
      96.8% of the patients. In 33 patients we used a ureteral catheter. The overall
      success rate was 90.3%. The 29% of the patients presented postoperative
      complications. CONCLUSIONS: Open pyeloplasty is the gold standard treatment of
      the UPJ obstruction in selected cases, mainly in children.

PMID- 10965573
TI  - [Evolution of microbial resistance to fluoroquinolones at a tertiary hospital].
AB  - Within the setting of a reference tertiary hospital such as Hospital La Fe, a
      retrospective study of major germs responsible for urinary infections and their
      susceptibility to fluoroquinolones was conducted between 1990-1998 in an attempt
      to quantify the increased resistance found in both in- and out-patients. The
      rationale for the study was the clinical evidence of resistance to those
      antimicrobials. E. coli continues to be the most frequently isolated micro
      organism in all types of urinary infections in both intra-hospital (50%) and
      extra-hospital infections (63%), followed by E. faecalis, P. mirabilis, and
      Klebsiella. When ward patients are compared to patients in Intensive Care Units
      (ICUs) a number of differences become apparent as regard to the isolated micro
      organisms. Current resistance to fluoroquinolones is about 23% for E. coli, 28%
      for E. faecalis, 6.5% for P. mirabilis, 5% for Klebsiella spp, 15% for
      Pseudomonas aeruginosa and 9% for Enterobacter spp. When these results are
      compared to those seen at the beginning of the '90s a highly significant increase
      is noted for E. coli (from 3 to 23%), E. faecalis (from 4.5 to 28%) and
      Pseudomonas aeruginosa (from 4 to 15%) with a much lower increase for the
      remaining micro-organisms. The reasons behind such an increase are numerous, the
      major one being the massive use of quinolones both in humans and animals, with
      variations based on age and geographic region. Generalisation of this major
      increase would lead to future use of fluoroquinolones based on susceptibility in
      culture, particularly in serious urinary infections.

PMID- 10965572
TI  - [Ureteral stenosis of uretero-ileal anastomosis].
AB  - Replacement plasty allows to perform oncology surgery while maintaining body
      image and preserving renal function. Entero-ureteral anastomosis is a significant
      element in this procedure where the main responsible for the loss of renal
      function are stenosis, infection and reflux. Our group has performed 206
      orthotopical vesical replacements (November 1981-November 1998), using a direct
      Wallace-type uretero-ileal anastomosis. An intussusception valve system was used
      as antireflux mechanism. The number of obstructions, rate of stenosis at the
      uretero-ileal junction and incidence of valve stenosis were all analyzed as part
      of the complications occurred over a follow-up period of 54 months (6-183).
      Findings included 6 stenosis at the uretero-intestinal junction and 2 at the
      intussusception valve. Two (3.8%) of the uretero-ileal stenosis were earlier and
      associated to fistula; one was treated with open surgery and one had a double J
      placed through antegrade percutaneous access. Of the remaining late four, only
      one was treated with a double J catheter while the other three had to be re
      operated. Stenoses of the valvular system (1.2%) were solved with open surgery.
      From our experience, we believe that direct uretero-ileal implantation with
      scraping of the ureter is a safe technique with little risk for stenosis at the
      uretero-ileal junction. Intussusception was used a antireflux system in all
      cases.

PMID- 10965574
TI  - [Treatment of genital herpes with alfa-2b interferon].
AB  - OBJECTIVE: To evaluate the efficacy and safety of the alfa-2b Interferon in the
      treatment of genital herpes. METHODS: 75 patients were treated with alfa-2b
      Interferon, 41 males (4 homosexuals) and 34 females, age range between 18 and 44
      years. The symptom and recurrences were evaluated. The Interferon was
      administered at 10 million/week intradermic during 4 to 12 weeks. RESULTS: The
      Interferon causes improvement in the symptoms and the recurrences were presented
      in 17 cases (22.6%). The mean in recurrences was 1.4 episodes per year.
      CONCLUSIONS: The alpha-2b Interferon lowers the symptoms, the recurrences in time
      and number. Allows pregnant women that have been treated to have a normal
      delivery.

PMID- 10965575
TI  - [Predictive factors of locally advanced disease in patients with prostatic cancer
      treated with neoadjuvant hormone therapy and radical prostatectomy].
AB  - AIM: To analyze the predictors of local adverse pathological findings (positive
      surgical margins and seminal involvement) in prostate cancer patients treated
      with neoadjuvant hormonotherapy and radical prostatectomy. PATIENTS AND METHODS:
      We studied seventy-eight patients treated with neoadjuvant androgen blockade
      prior to radical prostatectomy between 1995 and 1998. Age, PSA, prostate volume
      determined by transrectal ultrasound and/or magnetic resonance imaging, clinical
      stage, Gleason score, duration of blockade, pathological stage and tumoral volume
      were analyzed. RESULTS: 34.6% of patients (27/78) had adverse pathology (odds:
      0.53). No significant differences were found in age, PSA, prostate volume,
      duration of blockade and Gleason score between organ-confined and locally
      advanced patients. Differences were found in tumor volume (p = 0.0001) but this
      was not different in order to positive or negative digital rectal examination (p
      = 0.5334). The efficacy for predicting pathological adverse findings was
      represented by ROC curves (PSA: 0.628, clinical stage: 0.612 and Gleason score:
      0.545). Predictive table of extracapsular disease for different PSA levels,
      clinical stage and Gleason score were developed. No variable predicted positive
      margins in logistic regression model. CONCLUSIONS: Clinical variables do not
      predict locally advanced disease in prostate cancer patients treated with
      neoadjuvant androgen blockade. This is associated with higher tumor volumes. The
      probability of positive margins or seminal involvement increases with PSA level
      and Gleason score.

PMID- 10965576
TI  - [Stage pT3 prostatic cancer after radical prostatectomy. Results in progression
      and survival].
AB  - PURPOSE: To analyse progression and survival after radical prostatectomy in
      patients with stage pT3 carcinoma of the prostate. MATERIAL AND METHODS: Between
      1986 and November 1998, we performed 372 radical prostatectomies, 74 of which
      were pT3N0 (19.8%), 43 pT3a and 31 pT3b (TNM 97). RESULTS: In patients with
      pathological stage pT3, we found any progression in 24 patients (32%), 8 in pT3a,
      and 16 in pT3b. In 10 of 24 pT3, there was local relapse or distant metastases.
      About the freedom from biochemical relapse survival rate, we found statistically
      differences between pT3a and pT3b (p < 0.0001). In pT3a patients, we found no
      differences between PSA levels > 20 ng/ml, versus < 20 (p = 0.415), and
      statistically differences between pathological Gleason 6 or greater, versus < 6
      (p = 0.048). However, we found no differences when we used both criteria (PSA and
      Gleason) (p = 0.195). CONCLUSIONS: We support for early adjuvant hormonal therapy
      in pT3b patients. In pT3a, the hormonotherapy may be used if appears biochemical
      failure, specially with adverse prognostic factors (PSA and Gleason).

PMID- 10965577
TI  - [Primary transitional carcinoma of the prostatic ductus].
AB  - Primary prostate transitional cell carcinoma is a very rare tumour originating in
      the transitional epithelial cells of the intraprostate periurethral ductus. Only
      17 of 829 patients diagnosed with prostate carcinoma were found to have the
      transitional cell variety. Eight (8) of those had pure transitional cell
      carcinoma and 9 a mixed presentation of acinar adenocarcinoma and transitional
      cell ductal carcinoma. Bladder origin of the tumour was ruled out in all cases.
      We report a retrospective study on the clinical behaviour of prostate
      transitional cell carcinoma. Compared to acinar carcinomas, few differences were
      found when age, symptoms, physical findings and imaging diagnosis were evaluated.
      Clinical presentation, DRE, PSA, metastatic spread and presence of supravesical
      obstructive uropathy where also studied to establish a diagnosis. Radiotherapy
      was the most frequently used therapeutical approach. Mean survival is 26.6 months
      (4-60 months) and there has been 11 death up to now. Compared to acinar forms,
      this tumour shows a hormone-resistant, aggressive biological behaviour with poor
      prognosis. Early diagnosis and radical surgery are the only options available to
      increase life expectancy for these patients.

PMID- 10965578
TI  - [Bladder amyloidosis: report of 2 cases].
AB  - Two cases of amyloidosis of the bladder are reported: 1) a 45 year old man with
      haematuria. Cystoscopic examination reveals several tumours in the wall of the
      bladder. Transuretral resection was performed and histopathological examination
      revealed primary amyloidosis. Systemic amyloidosis was excluded. He was treated
      with oral colchicine with success. 2) a 71 year old male with diagnosis of
      rheumatoid arthritis and systemic amyloidosis visited our hospital with massive
      haematuria. Transuretral resection was unsuccessful and was necessary surgical
      ligation of hypogastric arteries.

PMID- 10965579
TI  - [Diffuse bladder hemangioma].
AB  - Contribution of a case report of diffuse bladder haemangioma developed since
      childhood, focusing on the diagnosis and management of these tumours and on the
      pathoanatomical analysis of the lesion. Literature review.

PMID- 10965580
TI  - [Report of 2 new cases of bladder inverted papilloma, one with them complicated
      with acute urinary obstruction].
AB  - Inverted papilloma is a rare tumour (2.2% of urothelial tumours) considered to be
      benign. The bladder is the most frequent site and growth tends to be endophytic
      towards the submucosa. Haematuria and obstruction symptoms appear to be the most
      typical clinical manifestations. Contribution of two cases of inverted bladder
      papilloma; one showing very unusual clinical development with relapsing acute
      urinary obstruction. Strict follow-up is recommended in spite of its benign
      behaviour as it may become associated to transitional cell carcinoma. Literature
      review on this tumoral entity in terms of etiology, clinical manifestations,
      diagnosis and treatment.

PMID- 10965582
TI  - [Ureteral triplication with vesicoureteral reflux and contralateral duplication].
AB  - We report a new case of ureteral triplication (type I in Smith's classification)
      with a grade V/V vesicoureteral symptomatic reflux to the lower group and non
      functional renal parenchima in this part of the kidney, associated with
      contralateral ureteral duplication. It was treated by left lower pole
      nephroureterectomy.

PMID- 10965581
TI  - [Pelvic lipomatosis: clinical review and report of 4 new cases].
AB  - First described by the end of the fifties, pelvic lipomatosis is an uncommon
      disease that develops as a result of an excessive proliferation of benign fat
      tissue within the perivesical and perirectal spaces. The compressive effect on
      the urinary, and to a lesser degree, the digestive and vascular structures result
      in the well-known symptoms. Diagnosis is reached through X-ray studies, primarily
      computerised tomography. Contribution of four new cases in young males diagnosed
      through imaging studies as well as biopsies in three of them. Evolution has been
      varying, with medical control of symptoms in two cases and renal function
      impairment due to upper obstructive uropathy in the other two.

PMID- 10965583
TI  - [Does primary melanoma of the bladder exist?].
AB  - Primary melanoma of the urinary bladder is a rare neoplasm to which very strict
      diagnostic criteria apply. Although reports of previous cases exist, these
      criteria have yet to be met. We report a case of a young lady from whom a
      malignant melanoma of the bladder was resected. This was presumed to be primary
      as detailed investigation failed to find any other site from which metastases
      could have originated. We discuss the diagnostic criteria of this entity and
      stress the difficulty in conclusively demonstrating that, despite some of these
      criteria being met, a lesion such as this is primary in origin. This case could
      be the longest surviving patient with primary melanoma of the bladder, however we
      will never be able to prove that spontaneous regression of an undiagnosed
      extravesical primary malignant melanoma did not occur.

PMID- 10965584
TI  - [Primary lymphoma of the prostate: report of a clinico-pathological case and
      review of the literature].
AB  - Lymphoma involving the prostate is rare, wether presenting as primary extranodal
      lymphoma or as a secondary spread to the prostate from other sites. There are
      less than 100 cases reported in the literature and accounts for 0.09-0.1%. The
      clinical presentation can be attributed to nodular hyperplasia or prostatic
      carcinoma. Criteria for primary prostatic lymphoma include: 1) tumor limited to
      the prostate and adjacent soft tissues. 2) the absence of lymph node involvement.
      3) a lymphoma free interval of at least 1 month. The evolution is rapid and the
      prognosis remains poor regardless of the patient age, histologic type, treatment,
      or clinical stage of disease at presentation. We report a case of a 65 years old
      male in which the incidental diagnosis of lymphoma of the prostate was performed
      in the adenomectomy. The clinico-pathological criteria and the histogenesis of
      this entity are described.

PMID- 10965585
TI  - High stakes testing: are the stakes too high?

PMID- 10965586
TI  - Memory in the deaf: a cross-cultural study in English and Japanese.
AB  - Deaf children who are learning to read are essentially learning a second language
      that may be transcribed in different ways, for example, using an alphabet, such
      as the Roman one used in written English, or logography, such as Japanese kanji.
      How do deaf adults from cultures using different writing systems memorize
      linguistic and visual material? Two experiments were carried out to answer this
      question. Two predictions were made: first, that Japanese deaf persons would
      outscore their English-language counterparts in memory for words, due to a
      possible direct processing from visual to semantic codes with kanji; second, that
      Japanese deaf persons would outscore their English-language counterparts in
      memory for abstract designs, due to prolonged use of a highly visual writing
      system. The first hypothesis was rejected; the second was accepted.

PMID- 10965587
TI  - Developing a tobacco survey for deaf youth.
AB  - Formidable barriers hinder use of standard data collection methods among deaf
      youth. Culturally and linguistically sensitive data collection strategies are
      needed to identify the unmet health and programming needs of this population.
      Unfortunately, researchers often fail to describe the issues involved in
      developing such targeted methods. The authors describe development of a
      culturally appropriate data collection instrument for a study of tobacco-related
      knowledge, attitudes, and practices among deaf youth. The instrument uses
      interactive multimedia technology to administer a questionnaire translated into
      the primary languages used by the Deaf. The procedures taken to accommodate this
      technology to these languages and to Deaf culture are described. This process
      yielded useful insights with respect to data collection not only among the Deaf,
      but among other frequently overlooked and underserved populations as well.

PMID- 10965588
TI  - Student perceptions and instructional effectiveness of deaf and hearing teachers.
AB  - The study examined the views of deaf and hard of hearing secondary-level students
      when asked about their preferences for deaf vs. hearing teachers. It also
      compared elementary- and secondary-level students' achievement scores based on
      the hearing status of their teachers. Deaf and hard of hearing secondary-level
      students showed greater preference for deaf teachers, with deaf students showing
      greater preference for deaf teachers than hard of hearing students did. No
      significant differences were found in the achievement levels of students based on
      differences in teacher hearing status. The study supports the limited research
      done in the past.

PMID- 10965589
TI  - Our decision on a cochlear implant.
AB  - This essay sets forth why we, the hearing parents of a profoundly deaf child,
      have chosen not to seek a cochlear implant for our daughter. In controversial
      matters, participants in a debate should set forth, as best they can, their
      prejudices and biases (which are not necessarily bad things), thereby allowing
      others to assess the degree, if any, to which their positions might be based on
      feelings (however understandable) vs. facts. I do so in this essay first by
      describing who we are and how we view deafness and Deaf culture, and then by
      discussing our daughter Margaret and how we see her being affected by our
      decision about cochlear implantation. I then briefly consider some unconvincing
      reasons offered against implants, and conclude with a few thoughts on the
      decision process.

PMID- 10965590
TI  - Measuring the quality of education: the involvement of bilingually educated deaf
      children.
AB  - The levels of involvement of six young deaf children were observed during three
      educational tasks. These levels were used as indicators of quality of education.
      The children were bilingually educated. The possible connection between language
      of instruction, type of task, teaching style, and level of involvement was
      studied. The children's observed overall level of involvement was high.
      Involvement was influenced by the type of educational task, but also by the
      teacher and by the language of instruction: Involvement was greater during
      activities led by the deaf teacher, using Sign Language of the Netherlands (SLN).
      Measurement of involvement of young deaf children turned out to be a good way to
      assess quality of education, not only for research purposes but in the context of
      general educational practice.

PMID- 10965591
TI  - Eye movement patterns of captioned television viewers.
AB  - Eye movement of six subjects was recorded as they watched video segments with and
      without captions. It was found that the addition of captions to a video resulted
      in major changes in eye movement patterns, with the viewing process becoming
      primarily a reading process. Further, although people viewing a specific video
      segment are likely to have similar eye movement patterns, there are also distinct
      individual differences present in these patterns. For example, someone accustomed
      to speechreading may spend more time looking at an actor's lips, while someone
      with poor English skills may spend more time reading the captions. Finally, there
      is some preliminary evidence to suggest that higher captioning speed results in
      more time spent reading captions on a video segment.

PMID- 10965592
TI  - Improving flexible thinking in deaf and hard of hearing children with virtual
      reality technology.
AB  - The study investigated whether rotating three-dimensional (3-D) objects using
      virtual reality (VR) will affect flexible thinking in deaf and hard of hearing
      children. Deaf and hard of hearing subjects were distributed into experimental
      and control groups. The experimental group played virtual 3-D Tetris (a game
      using VR technology) individually, 15 minutes once weekly over 3 months. The
      control group played conventional two-dimensional (2-D) Tetris over the same
      period. Children with normal hearing participated as a second control group in
      order to establish whether deaf and hard of hearing children really are
      disadvantaged in flexible thinking. Before-and-after testing showed significantly
      improved flexible thinking in the experimental group; the deaf and hard of
      hearing control group showed no significant improvement. Also, before the
      experiment, the deaf and hard of hearing children scored lower in flexible
      thinking than the children with normal hearing. After the experiment, the
      difference between the experimental group and the control group of children with
      normal hearing was smaller.

PMID- 10965593
TI  - 5 alpha-reductase in intact DU145 cells: evidence for isozyme I and evaluation of
      novel inhibitors.
AB  - The epithelial-like human prostatic carcinoma cell line DU145, which expresses 5
      alpha-reductase type I isozyme, was used to test a series of potential 5 alpha
      reductase inhibitors. The exclusive expression of the type I isozyme was
      confirmed by PCR and subsequent DNA sequence analysis. Culture conditions were
      optimized for high conversion rates. Using this whole cell assay finasteride,
      4MA, and 65 steroidal and non-steroidal compounds synthesized in our group were
      tested for their inhibitory activity. Inhibitors with IC50 values in the
      nanomolar range could be identified.

PMID- 10965595
TI  - Azagrevellins, Part I. Grevellin analogs with affinity to the N-methyl-D
      aspartate (glycine site) receptor, a novel lead structure.
AB  - A series of piperidine-2,3,5-triones (azagrevellins) has been prepared. A new
      synthesis has been introduced using the rearrangement of spiroepoxides in the
      presence of triethyloxonium tetrafluoroborate. The binding affinity toward the N
      methyl-D-aspartate (glycine site) receptor has been measured to provide a basis
      for more detailed structure-activity studies. Azagrevellin 18d showed the highest
      binding potency.

PMID- 10965594
TI  - Effect of flavonol derivatives on the carrageenin-induced paw edema in the rat
      and inhibition of cyclooxygenase-1 and 5-lipoxygenase in vitro.
AB  - Alkoxyflavonols were synthesized by the Algar-Flynn-Oyamada (AFO) cyclization of
      chalcones. Hydroxyflavonols were prepared by dealkylation of methoxyflavonols by
      refluxing in hydroiodic acid. The alkoxyflavonols 3-hydroxy-2-(2,3,4
      trimethoxyphenyl)-4H-chromen-4-one (6), 2-(4-ethoxyphenyl)-3-hydroxy-4H-chromen-4
      one (7), 2-(4-butoxyphenyl)-3-hydroxy-4H-chromen-4-one (10), and 2-(3-n
      butoxyphenyl)-3-hydroxy-4H-chromen-4-one (11) as well as the trihydroxy
      derivative 3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one (18) displayed
      high anti-inflammatory activity in carrageenin-induced rat paw edema.
      Additionally, the inhibition of enzymes of the arachidonic acid cascade by the
      derivatives was investigated in vitro. In contrast to the natural compound
      quercetin, the compounds were more potent inhibiting cyclooxygenase-1 than 5
      lipoxygenase except for 3-hydroxy-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one
      (5). No correlation between the anti-inflammatory activity in the rat paw edema
      test and the inhibition of 5-lipoxygenase or cyclooxygenase-1 could be observed.
      In conclusion, the present results suggest that other effects than inhibition of
      these enzymes of the arachidonic acid cascade are important for the anti
      inflammatory activity of the investigated alkoxyflavonols.

PMID- 10965596
TI  - The cytotoxicity of symmetrical and unsymmetrical bis(thiosemicarbazones) and
      their metal complexes in murine and human tumor cells.
AB  - A number of thiosemicarbazones have been tested previously and herein are
      included three bis(thiosemicarbazones) for comparison to the previous
      derivatives. In general the uncomplexed thiosemicarbazones were more potent in
      the cytotoxic screens than the bis(thiosemicarbazone) except in the murine L1210
      and the human colon SW480 screens. Mode of action studies have only demonstrated
      slight differences in the effects of the two types of compounds on nucleic acid
      metabolism. The symmetrical and unsymmetrical bis(thiosemicarbazones) complexes
      of copper, nickel, zinc, and cadmium have been examined to compare them to the
      heterocyclic N(4)-substituted thiosemicarbazones metal complexes. These new
      derivatives demonstrated excellent activity against the growth of suspended
      lymphomas and leukemias although it should be pointed out that generally they
      were not as active as the copper complexes of N(4)-substituted
      thiosemicarbazones. Nevertheless, selected bis(thiosemicarbazones) complexes were
      active against the growth of human lung MB9812, KB nasopharynx, epidermoid A431,
      glioma UM-86, colon SW480, ovary 1-A9, breast MCK-7, and osteosarcoma Saos-2. In
      human HL-60 promyelocytic leukemia cells the complexes preferentially inhibited
      DNA and purine syntheses over 60 min. The regulatory enzyme of the de novo purine
      pathway, IMP dehydrogenase, appeared to be a major target of the complexes.
      However, minor inhibition of the activities of DNA polymerase alpha, PRPP-amido
      transferase, ribonucleotide reductase, and nucleoside kinases occurred over the
      same time period. No doubt these effects of the complexes on nucleic acid
      metabolism were additive since the d[NTP] pool levels were reduced after 60 min
      as was DNA synthesis. The symmetrical and unsymmetrical bis(thiosemicarbazones)
      and their metal complexes did not cause as severe DNA fragmentation as the
      heterocyclic N(4)-substituted thiosemicarbazone metal complexes; furthermore,
      their metabolic effects in the tumor cell were more focused on a single synthetic
      pathway.

PMID- 10965597
TI  - Diazabicyclo[3.3.1]nonanone-type ligands for the opioid receptors.
AB  - Previously 2,4-dipyridine substituted 3,7-diazabicyclo[3.3.1]nonanone diesters
      were found to have a high affinity and selectivity towards the kappa-opioid
      receptor. The purpose of this study was to check the influence of substituents at
      position N3 on the affinity to the mu-, delta-, and kappa-receptors. Whereas a
      phenylethyl group is able to create affinity to the mu-receptor, small
      substituents such as a hydrogen or a methyl group are responsible for a high
      affinity to the kappa-receptor. In addition, a dimeric compound was found to have
      affinity to the kappa-receptor. Although all compounds will bear at least one
      positive charge under physiological conditions they show a considerable
      lipophilicity, indicating the possibility of passing the blood-brain barrier.

PMID- 10965598
TI  - Pyridazines 91. Synthesis of substituted tri- and tetracyclic compounds bearing a
      pyridazine core and their biological evaluation as antimycobacterial agents.
AB  - Starting from substituted 3,6-dichloropyridazine-4-carboxamides (2, 3) tri- and
      tetracyclic compounds (4, 5) could be smoothly prepared. Structural modifications
      of interest with regard to biological activity were performed by N-alkylation and
      reductive dehalogenation. The new substituted heterocyclic compounds were
      screened as antimycobacterial agents; the influence of the substitution pattern
      on activity is discussed.

PMID- 10965599
TI  - [More attention in everyday life to preventive services].

PMID- 10965600
TI  - [Ethics and alcohol consumption].

PMID- 10965601
TI  - ["Epidemiologia e Prevenzione" and the multinationals of tobacco].

PMID- 10965602
TI  - [Clinical attitude and epidemiological reasoning].

PMID- 10965603
TI  - [A short trip to Philip Morris Archives].

PMID- 10965604
TI  - [Researchers did not know].

PMID- 10965607
TI  - [Guidelines on drug donations are not sufficient for effective coordination: the
      case of Mostar in former Yugoslavia].
AB  - This article deals with the problem of restoring and repairing the supply and
      distribution of drugs, a vital service damaged by long-term conflicts. During the
      post-war situation in Bosnia the Authors have been actively involved in the
      implementation of the Drugs Management Programme whose principal aims were as
      follows: 1) rationalise the arrival and storage of new drugs; 2) utilise
      efficiently the stocks of drugs and medical materials at hand; 3) cope with the
      steady post-war decrease of humanitarian aid drug donations; 4) eliminate the
      large quantities of expired or inappropriate drugs. The experience stresses the
      need that all EU countries adopt as far as possible the strict WHO guidelines in
      their donations to countries in emergency situations. However a very flexible
      organisation should be set up immediately after the conflict in order to tackle
      all the problems that, no doubt, will appear in the aftermath of a war.

PMID- 10965605
TI  - [Methodological issues and first results of a record linkage between AIDS and
      Cancer Registries in Italy].
AB  - We report herein, the first results of a record linkage between the Italian AIDS
      Registry and 13 population-based Cancer Registries (about 8-million population in
      1991). An anonymous linkage process was carried out on about 339,000 cancer
      notifications and 6,067 AIDS ones reported between 1982 and 1994. Out of 243
      Kaposi's sarcomas (KS) below age 50 years recorded at either type of registry, 90
      (37%) were reported as such by both. Sixty-eight percent of individuals with KS
      at Cancer Registries could be identified at the AIDS Registry. Sixty-two percent
      of individuals with KS and 65% of individuals reported as having non-Hodgkin's
      lymphoma (NHL) at RAIDS could be also found at Cancer Registries. Among 6,067
      persons with AIDS 15-69 years old, observed and expected numbers of cancer and
      age-standardised incidence ratios (SIR) on a total of 25,759 person-years were
      computed. Significantly increased SIR was found for Hodgkin's disease (8.9; 95%
      CI: 4.4-16.0), invasive carcinoma of the cervix uteri (15.5; 95% CI: 4.0-40.1),
      and non-melanomatous skin cancer (3.0, 95%, CI: 1.3-5.9). As in previous studies,
      KS and NHL were greatly increased (SIR = 1,300 and 59, respectively). The risk
      for all cancer types, after exclusion of KS and NHL, was approximately twice the
      risk of the general population. An increased SIR of Hodgkin's disease in persons
      with AIDS is thus confirmed, though many-fold smaller than for NHL. An
      association with invasive carcinoma of the cervix is also shown at a population
      level. These data indicate the potential of AIDS and Cancer Registries for
      improving cancer assessment in individuals with HIV/AIDS and elucidating the role
      of immune system on cancer onset.

PMID- 10965606
TI  - [High risk of pleural mesothelioma among the state railroad carriage repair
      workers].
AB  - Exposure to asbestos in a facility for the repair of railroad carriages in
      Bologna was initially studied in 1980, when the Local Health Unit started a
      program of primary prevention on request of the Unions. At that time workers
      employed in jobs with high exposure to asbestos were identified. The mortality
      experience of these 173 subjects was investigated from 01.01.1979 through
      31.12.1997, and compared to that of the population of Emilia Romagna. SMR for all
      causes was 69, with upper limit of the confidence interval lower than 100; this
      was largely due to a significant decrease of cardiovascular mortality. Among
      neoplasms, there was a significant excess of pleural mesothelioma (6 observed,
      0.09 expected); one more subject died for peritoneal mesothelioma and one for
      malignant mesothelioma of unspecified site. About half of the subjects deceased
      for neoplastic disease (8/17) were affected by mesothelioma.

PMID- 10965608
TI  - [Prevention is a matter of building in and implementing safety measures: crimes
      committed in Porto Marhera].

PMID- 10965610
TI  - [A table for comparing the INAIL and the ISTAT classification of economic
      activity].

PMID- 10965609
TI  - [Early retirement for ex asbestos workers. The role of the National Insurance
      Institute for work Accidents].

PMID- 10965612
TI  - [Nevus under double suspicion].

PMID- 10965613
TI  - A clinical study of surgical treatment of patients with carcinoma of the cervical
      esophagus extending to the thoracic esophagus.
AB  - OBJECTIVE: We studied optimum surgery for carcinoma of the cervical esophagus
      extending to the thoracic esophagus (Ce-Ut carcinoma). METHODS: Subjects were 13
      patients diagnosed with Ce-Ut carcinoma treated at our institute from January
      1989 to December 1998. Clinicopathologic information such as surgical procedures,
      pathologic findings, and postoperative complications were analyzed. RESULTS: In
      10, laryngoesophagectomy was conducted due to tracheal invasion by the tumor. In
      7, mediastinal tracheostomy was done because of the extended resection of the
      proximal trachea. In 3, the larynx was preserved and, in 2, cricopharyngeal
      myotomy was added. Lymph node metastasis was found only in the neck and the upper
      mediastinum at surgery and recurrences were all lung metastasis. The incidence of
      postoperative complications was very high (76.9%), and 1 patient died due to
      widespread tracheal necrosis. The cumulative 5-year survival rate for the group
      was 33.3% and that for the 9 curative cases was 50%, but most of the cases who
      underwent noncurative resection and/or who received preoperative therapy for
      widespread invasion to surrounding organs died within a year. CONCLUSION: The
      prognosis of patients who undergoing curative extended resection of the proximal
      trachea and suitable lymph node dissection in the neck and upper mediastinum may
      improve, and larynx-preserving surgery is recommended for patients without
      tracheal invasion. Despite preoperative chemoradiotherapy, the prognosis of
      patients with widespread invasion to surrounding organs was very poor, and
      clinical studies on new therapeutic strategies for these advanced cases are
      needed to improve the prognosis of Ce-Ut carcinoma patients.

PMID- 10965611
TI  - [A advisory board for conscious access to therapies].

PMID- 10965614
TI  - Valved conduit operation for aortic regurgitation associated with Behcet's
      disease.
AB  - OBJECTIVES: Aortic regurgitation associated with Behcet's disease is rare, and
      prosthetic valve detachment after aortic valve replacement is one of the most
      serious complications reported. We have investigated the surgical results of
      valved conduit operation in 8 patients. METHODS: Between 1987 and April 1999, 8
      patients underwent surgery. There were 7 males and 1 female, and their ages
      ranged from 33 to 60 years (mean, 48 +/- 10 years). The valved conduit procedure
      was a modified Bentall operation. RESULTS: One patient died of arrhythmia during
      the hospital stay. The follow-up period in the other 7 patients ranged from 1 to
      138 months after surgery (mean, 74 months). None of these 7 patients died during
      the follow-up period. Valve detachment needing redo-operation occurred in 1
      patient, and he underwent a valved conduit operation again. CONCLUSIONS: Valved
      conduit reconstruction is indicated in patients with aortic regurgitation caused
      by Behcet's disease, in whom prevention of valve detachment is difficult even by
      current valve fixation methods.

PMID- 10965615
TI  - Induction of acute-phase reactive substances during open-heart surgery and
      efficacy of ulinastatin. Inhibiting cytokines and postoperative organ injury.
AB  - OBJECTIVE: A systemic inflammatory response after open-heart surgery using
      cardiopulmonary bypass may be responsible for postoperative organ dysfunction.
      Ulinastatin, a protease inhibitor, plays an important role in host defense under
      periods of stress. METHODS: We studied the efficacy of ulinastatin on changes in
      acute-phase reactive substances during and after open-heart surgery. Patients
      undergoing open-heart surgery were divided into an ulinastatin group (Group U)
      and a control group (Group C). In Group U, we introduced 600,000 units of
      ulinastatin into a priming solution for cardiopulmonary bypass, 300,000 units
      into a cardiopulmonary bypass circuit at the removal of aortic cross-clamping,
      and 300,000 units a day for 5 days following surgery. RESULTS: Immediately after
      cardiopulmonary bypass, alpha 1-antitrypsin levels decreased significantly in
      both groups, and increased significantly on the second day after surgery.
      Ulinastatin levels decreased after cardiopulmonary bypass in Group C.
      Significantly high levels of ulinastatin were obtained in Group U. Interleukin-6,
      interleukin-8, and polymorphonuclear elastase were markedly induced, and high
      levels of plasma concentration continued for several days after surgery. At all
      sample points, these concentrations in Group U tended to be lower than those in
      Group C. A significantly positive correlation was seen between the maximum levels
      of interleukin-8 and polymorphonuclear elastase, but these cytokine and
      polymorphonuclear elastase levels did not correlate with parameters such as the
      duration of anesthesia, surgery, cardiopulmonary bypass, or aortic cross
      clamping. CONCLUSIONS: Our study suggests that high-dose ulinastatin
      administration to maintain a sufficient concentration of circulating protease
      inhibitors may suppress overinduction of cytokines and polymorphonuclear elastase
      in open-heart surgery.

PMID- 10965616
TI  - Efficacy of leukocyte-depleted terminal blood cardioplegia in congenital heart
      disease.
AB  - OBJECTIVE: Activated leukocytes and their products play a significant role in
      reperfusion injury and cause microvascular occlusion--the 'no-reflow phenomenon'-
      which decreases coronary blood flow after the release of the aortic cross-clamp
      during open-heart surgery. This study was designed to evaluate the efficacy of
      leukocyte-depleted terminal blood cardioplegia in patients with right ventricular
      pressure or volume overloaded congenital heart disease undergoing intracardiac
      repair. SUBJECTS AND METHODS: Fourteen infants and children undergoing
      intracardiac repair for congenital heart defects were the subjects in this study.
      Leukocyte-depleted terminal blood cardioplegia was employed in seven patients
      (Group I). For the control, terminal blood cardioplegia with leukocytes was
      employed in seven patients (Group II). In order to evaluate the myocardial
      anaerobic metabolism, the arteriovenous difference in the pyruvate and lactate
      levels was compared between both groups. Blood samples were taken simultaneously
      from both the arterial limb of the bypass circuit and the coronary sinus
      immediately after, and at 5, 10, and at 20 minutes after, the release of the
      aortic cross-clamp. RESULTS: The coronary arteriovenous difference in the
      pyruvate and lactate levels demonstrated that the myocardial anaerobic metabolism
      in Group II was significantly higher than in Group I. The delta excess lactate
      demonstrated that myocardial hypoxia in Group II persisted significantly longer
      than in Group I. There was a tendency for the creatine kinase-MB level at 6 hr
      after surgery to be lower in Group I than in Group II. CONCLUSION: Leukocyte
      depleted terminal blood cardioplegia may reduce the myocardial anaerobic
      metabolism in patients with right ventricular pressure or volume overloaded
      congenital heart disease undergoing intracardiac repair.

PMID- 10965617
TI  - Clinical effects of ventricular assist system in end-stage cardiac failure.
      Advantages of left ventricular blood drainage for recovery from cardiac
      dysfunction.
AB  - OBJECTIVES: Heart transplantation is extremely limited currently in Japan. As a
      consequence ventricular assist system implantation is employed the patient falls
      into end-stage cardiogenic shock. This preliminary report describes our initial
      clinical experience with use of 2 kinds of ventricular assist system for 13
      Japanese patients. METHODS: 7 patients were supported by a left ventricular
      assist system with blood drainage from the left atrium (LA drainage Group) using
      a Toyobo ventricular assist system, while another 6 patients were supported by a
      left ventricular assist system with blood drainage from the left ventricle (LV
      drainage Group) using the Toyobo ventricular assist system (1 patient) or TCI
      LVAS (5 patients). RESULTS: The average duration of ventricular assist system
      support in the LV drainage Group was 112 days including two on-going patients
      (now at 39 days and 241 days) and in the LA drainage Group was 49 days. The
      average left ventricular ejection fraction at 3 weeks after ventricular assist
      system implantation was improved from 12.3 to 54% using the TCI-LVAS and from 14
      to 33% using the Toyobo ventricular assist system with drainage from the left
      ventricle. However, this was decreased from 20 to 10% using the Toyobo
      ventricular assist system with drainage from the left atrium. The ventricular
      assist system was explanted in 4 patients (31%) with recovery of cardiac
      dysfunction and 3 were long survivors. The 2 on-going patients are awaiting heart
      transplantation. Thus the current survival rate overall is 38%. The survival rate
      (67%) is excellent in the LV drainage Group including 2 long survivors after
      explantation. CONCLUSION: Ventricular assist system support with drainage from
      the left ventricle seems to be more advantageous for cardiac functional recovery
      than from the left atrium for end-stage heart failure.

PMID- 10965618
TI  - Successfully treated descending necrotizing mediastinitis through
      mediansternotomy using a pedicled omental flap.
AB  - A 21-year-old man with an oropharyngeal abscess admitted to our institution was
      initially treated with systemic antibiotics but was referred to our department
      when his condition rapidly deteriorated. His respiratory insufficiency required
      circulatory support. A computed tomographic scan showed a parapharyngeal abscess
      descending into the mediastinum with multiple right-side capsulized empyema and
      pericardial effusion. We conducted emergency surgery through a mediansternotomy
      using a pedicled omental flap. Postoperative clinical and radiologic assessment
      showed a normal chest X-ray and primary wound healing without sternal dehiscence.
      Mediansternotomy using a pedicled omental flap offers excellent exposure for a
      complete one-stage operation with debridement of all affected tissues of the
      subauricular region, the mediastinum, and both pleural cavities. We conclude that
      this method yields good results for patients with acute widespread descending
      necrotizing mediastinitis.

PMID- 10965619
TI  - Infective endocarditis affecting both systemic and pulmonary circulations
      predisposed by a ventricular septal defect.
AB  - A 39-year-old woman was admitted to our hospital presenting persisting fever. An
      echocardiographic examination showed severe aortic and mitral valve regurgitation
      with moderate tricuspid regurgitation. Small left-to-right shunt through the
      ventricular septal defect was identified. Vegetation was also detected on the
      tricuspid, mitral, and aortic valves. At one month after admission, the patient
      showed sudden onset of headache and abdominal pain. A computed tomographic scan
      demonstrated cerebral and splenic infarction. A pulmonary perfusion scintigram
      demonstrated perfusion defects in left-S1 and right-S6 regions. At 4 months after
      admission, as operation was performed. The aortic valve was replaced with a #23
      mm CarboMedics prosthesis and the mitral valve with a #29 mm Carbo Medics
      prosthesis. Tricuspid valve plasty was performed, with closure of He laceration
      and perforation of the anterior leaflet combined with a commissuroplasty,
      according to Kay's method. Ventricular septal defect was closed with a bovine
      pericardial patch. She was discharged at 19 days after the operation, and is
      leading a good life. Pervasion of the organism seemed to be initiated from the
      mitral valve which was conveyed by the blood stream to the aortic valve, and to
      the tricuspid valve through the ventricula septal defect. Left heart evaluation
      may be important in cases with infective endocarditis and ventricula septal
      defect.

PMID- 10965620
TI  - Descending aortic aneurysm with Takayasu's disease.
AB  - A 69-year-old woman with Takayasu's disease was referred to our hospital for
      surgical treatment of a descending aortic aneurysm. Preoperative angiography and
      computed tomography revealed abdominal aortic stenosis and severe calcification
      in the descending aorta. The abdominal aorta was first replaced, since the aortic
      stenosis would have disturbed blood flow to the abdominal organs during
      extracorporeal circulation, which would be needed for subsequent thoracic
      surgery. The descending aortic aneurysm was then resected under femoro-femoral
      bypass. Since the descending aorta was severely calcified, two occlusion balloon
      catheters were used to clear the aorta. After aortic walls just proximal and
      distal to the aneurysm were decalcified, a short prosthetic tube graft was
      anastomosed. Only 2 pairs of intercostal arteries were sacrificed and paraplegia
      was prevented. Vascular lesions must thus be accurately evaluated and suitable
      procedures selected in surgically treating Takayasu's disease.

PMID- 10965621
TI  - Clinical experience of milrinone as a pharmacological bridge to heart
      transplantation.
AB  - A 19-year-old man with idiopathic dilated cardiomyopathy developed cardiogenic
      shock. A HeartMate left ventricular assist device was inserted as an emergency
      procedure, but removed after 189 days due to sepsis related to the device.
      Intravenous milrinone was administered because of recurrence of heart failure,
      and as a result the symptoms disappeared and the urinary output increased.
      Echocardiography showed improvement in the left ventricular ejection fraction.
      Subsequently, the patient successfully underwent heart transplantation. Milrinone
      was effective as a pharmacological bridge to heart transplantation in this
      patient with terminal and critical heart failure after removal of a left
      ventricular assist device.

PMID- 10965622
TI  - Extended operation for non-small-cell lung cancer invading into the liver.
AB  - Direct invasion of a lung cancer into the liver is rare. Here we report a case
      with a non-small-cell lung cancer invading through the diaphragm into the liver.
      A 77-year-old woman was admitted to our hospital with a complaint of right chest
      pain. Chest X-ray showed a 10-cm shadow in the right lower lung field. Chest CT
      demonstrated a large heterogeneous tumor located in the right lower lobe of the
      lung. Chest MRI revealed the tumor directly invading through the diaphragm into
      the liver. Bronchoscopic biopsy revealed squamous cell carcinoma. Surgical
      resection was performed to prevent intrapulmonary rupture of the necrotic
      contents. A right lower lobectomy was performed with partial resection of the
      diaphragm, liver and chest wall. Marlex mesh was used to reconstruct the
      diaphragm and chest wall. The patient was discharged on the 23rd postoperative
      day without complications, but died 4 months later from bilateral pulmonary
      metastases. Invasion to the diaphragm and liver may increase the risk for
      hematological spread. Although there are limited reports on treatment options,
      combined resection of the liver should be considered in the case of non-small
      cell lung cancer invading the liver, particularly in c-N0M0 case.

PMID- 10965623
TI  - Intrapulmonary mature teratoma.
AB  - Intrapulmonary teratoma is reported in a 22-year-old male. A chest X-ray in a
      physical examination showed a round shadow in the left hilum of a 22-year-old man
      who, on admission, reported slight malaise and a decrease in body weight.
      Computed tomographic scan and magnetic resonance imaging of the chest showed a
      heterogeneously dense cystic lesion. The preoperative diagnosis was anterior
      mediastinal teratoma, and the tumor was located in the anterior segment of the
      left upper lobe after thoracotomy. Segmentectomy of the left upper division
      showed a 4.0 x 3.5 cm tumor diagnosed as an intrapulmonary mature teratoma--the
      27th such case reported in the English-language literature. This is, to the best
      of our knowledge, the first intrapulmonary teratoma involving magnetic resonance
      imaging.

PMID- 10965624
TI  - Spontaneous esophageal rupture treated by conservative therapy.
AB  - The prognosis of spontaneous esophageal rupture of the esophagus worsens over
      time from disease onset to treatment and, in severe cases, may require surgery to
      save the patient's life. Patients appearing at the hospital considerably after
      esophageal perforation have no appropriate surgical alternatives and face poor
      prospects. We conservatively treated a severe case following 2-day lapse of after
      disease onset, managing a favorable outcome. A 58-year-old man who developed
      upper abdominal and back pain after vomiting from drinking was transferred to our
      institute in an emergency due to pain intensifying 2 days after the symptom
      onset. Chest X-ray revealed a large quantity of bilateral pleural effusion
      similar to gastrointestinal content, which we withdrew through intrathoracic
      drainage. Esophagography showed perforation of the esophagus. The patient's poor
      general condition, including septic shock and adult respiratory distress
      syndrome, contraindicated radical surgery, so we instituted conservative therapy
      such as continuous thoracic drainage hyperalimentation. Oral intake was started
      in month 4 after admission. The patient was discharged in good general condition
      7 months after onset.

PMID- 10965625
TI  - Aneurysm of the left sinus of Valsalva causing aortic, mitral regurgitation and
      myocardial ischemia.
AB  - An aneurysm of the left sinus of Valsalva producing aortic and mitral
      regurgitation with myocardial ischemia was treated successfully by reconstructing
      the left coronary sinus while preserving the aortic cusp combined with coronary
      artery bypass grafting. Aortic and mitral regurgitation occurred due to
      distortion of the left aortic cusp by a huge aneurysm that also compressed and
      obstructed the main trunk of the left coronary artery. The postoperative course
      was uneventful and follow-up showed aortic and mitral regurgitation to be absent
      and the coronary graft to be patent. Aortic valve-sparing surgery thus proved to
      be an appropriate procedure for this case.

PMID- 10965626
TI  - Transsternal bilateral thoracotomy for pericardiectomy after coronary artery
      bypass grafting.
AB  - Surgery for constrictive pericarditis was conducted through a transsternal
      bilateral thoracotomy in a 45-year-old man who developed the condition 12 months
      after coronary artery bypass grafting with left internal thoracic artery and vein
      grafts. The grafts ran just beneath the sternum. To avoid injury to the bypass
      grafts during sternotomy and mediastinal dissection, we conducted a transsternal
      bilateral thoracotomy, which provided excellent exposure of the heart. Complete
      pericardiectomy was done safely without cardiopulmonary bypass. Constrictive
      pericarditis following cardiac surgery is an uncommon complication posing
      difficult problems for the surgeon. The presence of a patent left internal
      thoracic artery bypass is particularly challenging. Transsternal bilateral
      thoracotomy is a useful approach in patients with constrictive pericarditis in
      whom a median sternotomy is contraindicated.

PMID- 10965627
TI  - Mitral valve plasty using artificial chordae in a 1.5-year-old boy with
      congenital mitral stenosis and absent anterolateral chordae.
AB  - A 1.5-year-old boy with refractory heart failure due to congenital mitral
      stenosis exhibited fusion of the anterolateral leaflets associated with moderate
      mitral regurgitation due to absent anterolateral chordae. Fused leaflets were
      incised and the mitral valve opening improved. Mitral regurgitation increased due
      to the absence of chordae, so 2 pairs of artificial chordae of 5-0 expanded
      polytetrafluoroethylene suture were anchored to the hypoplastic anterolateral
      papillary muscle, then attached to the free margin of incised leaflets.
      Postoperative examination showed improved mitral opening without exacerbated
      mitral regurgitation.

PMID- 10965628
TI  - Introduction to the special section on stepped care models in psychotherapy.
AB  - Not all patients need the same type and intensity of intervention. Some may be
      helped greatly by reading a self-help book, watching an instructional video, or
      using a computer program. Others could benefit from a brief psychoeducational
      group conducted by a paraprofessional, and still others may require long-term
      individual treatment from a highly trained professional therapist with
      specialized expertise. In an environment of limited resources, it makes sense to
      provide all the time, expertise, and individual attention a patient needs, but
      not more. Stepped care models represent attempts to maximize the effectiveness
      and efficiency of decisions about allocation of resources in therapy. This
      article introduces a special section addressing these resource allocation issues
      in the context of prevalent disorders (e.g., generalized anxiety disorder, panic
      disorder, eating disorders, and alcohol dependence) for which empirically
      supported psychosocial treatments are available.

PMID- 10965629
TI  - Recommendations for a cost-offset model of psychotherapy allocation using
      generalized anxiety disorder as an example.
AB  - As inexpensive interventions gain empirical support, there is an increasing risk
      that such data may be used by health maintenance organizations to unfairly
      restrict the number and type of therapy sessions reimbursed for all clients, even
      those less likely to benefit from economical treatments. As a result, it is
      important to identify clients who may not respond to specific therapies and to
      empirically support ways to treat them. Successful treatment of nonresponders is
      also valuable because predictors of treatment failure tend to predict cost
      related to medical and disability expenses. Using generalized anxiety disorder as
      an example, this article suggests a flexible and comprehensive approach to cost
      benefit analysis in psychotherapy that includes clients who may not improve in
      response to current data-based interventions. In addition, suggestions are made
      for the identification of alternative treatment approaches, and a potential
      treatment allocation model is recommended.

PMID- 10965630
TI  - Empirically supported treatments for panic disorder: costs, benefits, and stepped
      care.
AB  - Treatment outcome findings suggest that cognitive-behavioral therapy (CBT) and
      pharmacotherapy offer similar short-term treatment gains for panic disorder and
      that CBT may afford more optimal maintenance of treatment gains without the need
      for ongoing treatment. However, efficacy is not the only consideration for
      patients, and because of limited health care resources, evaluation of the cost
      benefit ratio of these treatments is important. In this article, the authors
      review estimates of the relative efficacy, acceptability, tolerability, and costs
      of these treatments; empirically examine the costs and outcome of cognitive
      behavioral and pharmacologic interventions as they are delivered in an outpatient
      clinic specializing in these treatments; and comment on how these data inform a
      stepped care model of treatment. Analysis of the "services" data indicated that
      CBT was at least equal to pharmacotherapy in terms of pretreatment severity and
      acute treatment outcome and that CBT is an especially cost-effective treatment
      option.

PMID- 10965631
TI  - Stepped care treatment for eating disorders.
AB  - A stepped care approach would link different patient needs to therapeutic
      modalities that range from simple advice to intensive inpatient care. Brief
      methods, including self-help and psychoeducation, may be effective for a subset
      of patients with bulimia nervosa and binge eating disorder. Identifying this
      subset remains a challenge. It is unclear how patients who fail to respond to
      evidence-based, first-line treatments should be treated. Given the absence of
      data on effective treatment of anorexia nervosa (AN), discussion of a stepped
      care approach is speculative. Because AN typically demands expert and sustained
      treatment, the lower levels of stepped care models are inapplicable for these
      patients. A stepped care approach poses methodological challenges for clinical
      research and raises important clinical issues, such as when to switch from 1
      level of treatment to another.

PMID- 10965632
TI  - Stepped care as a heuristic approach to the treatment of alcohol problems.
AB  - A stepped care approach to treatment decisions for alcohol problems consists of
      the application of decision rules derived from practice in other areas of health
      care. The treatment used should be (a) individualized, (b) consistent with the
      research literature and supported by clinical judgment, and (c) least restrictive
      but still likely to be successful. Used in this way, stepped care emphasizes
      serving the needs of clients efficiently but without sacrificing quality of care.
      Issues concerning stepped care are discussed, and the application of a stepped
      care approach to alcohol treatment services is described.

PMID- 10965633
TI  - Stepped care: doing more with less?
AB  - Several issues concerning stepped care are discussed: the constraints of using
      Diagnostic and Statistical Manual of Mental Disorders diagnoses in randomized
      clinical trials (RCTs), the importance of basic and process research, the
      unintended negative effects of exaggerated claims of effectiveness and
      efficiency, the limits of RCTs in evaluating improvement and deterioration, the
      self-correcting nature of stepped care, the link between stepped care and
      empirically supported treatments, clinical judgment in clinical work, the concept
      of the least restrictive alternative, the costs of using low-intensity but
      ineffective psychosocial treatments, and the costs of both ineffective and
      effective psychotropic drug therapy. An analysis of stepped care can lead to an
      appreciation that the dialectic operating between science and practice affords an
      opportunity to synthesize the seemingly irreconcilable standards and needs of
      researchers and clinicians.

PMID- 10965634
TI  - Insomnia and the eye of the beholder: are there clinical markers of objective
      sleep disturbances among adults with and without insomnia complaints?
AB  - Previous findings suggest that some who report insomnia sleep well, whereas some
      noncomplaining individuals sleep rather poorly. This study was conducted to
      determine if mood, anxiety, and sleep-related beliefs might relate to perceived
      sleep disturbance. Thirty-two women and 32 men (aged 40-79 years) with primary
      insomnia and an aged-matched sample of 61 normal sleepers (31 women, 30 men)
      completed 6 nocturnal sleep recordings, as well as the Beck Depression Inventory
      (BDI), the Trait portion of the State-Trait Anxiety Inventory (STAI-2), and the
      Dysfunctional Beliefs and Attitudes About Sleep Questionnaire. Sleep and
      interview data were used to subdivide the majority of the sample (n = 108) into
      objective normal sleepers and subjective insomnia sufferers who seemingly slept
      well and subjective normal sleepers and objective insomnia sufferers who slept
      poorly. The 2 subjective subgroups showed the most marked differences on most of
      the psychometric measures. The findings suggest that the psychological factors
      scrutinized in this study may mediate sleep satisfaction and/or predict objective
      sleep difficulties.

PMID- 10965635
TI  - Effectiveness of exposure and ritual prevention for obsessive-compulsive
      disorder: randomized compared with nonrandomized samples.
AB  - The efficacy of exposure and ritual prevention (EX/RP) for reducing symptoms of
      obsessive-compulsive disorder (OCD) has been demonstrated in several randomized
      controlled trials (RCTs). However, procedures used in these studies to maximize
      experimental control may have limited their generalizability to typical clinical
      practice. Treatment outcome data from 110 clinical patients receiving EX/RP on an
      outpatient fee-for-service basis were compared with findings from 4 RCTs of
      EX/RP. Adult patients in the clinical sample were not excluded because of
      treatment history, concomitant pharmacotherapy, psychiatric comorbidity, age, or
      OCD severity. Clinical patients achieved substantial and clinically meaningful
      reductions in their OCD and depressive symptoms following EX/RP, which were
      comparable with those reported in the RCTs. Findings indicate that EX/RP is a
      potent treatment for OCD, and its benefits are not limited to select patient
      samples.

PMID- 10965636
TI  - Cognitive and family therapies for adolescent depression: treatment specificity,
      mediation, and moderation.
AB  - The specificity of cognitive and family therapies, and potential treatment
      mediators and moderators, was examined in a randomized clinical trial for
      adolescent depression. After acute treatment, cognitive-behavioral therapy (CBT)
      exerted specific effects on cognitive distortions relative to either systemic
      behavioral family therapy (SBFT) or nondirective supportive therapy (NST). At 2
      year follow-up, SBFT was found to impact family conflict and parent-child
      relationship problems more than CBT; NST and CBT tended to show a greater
      reduction in anxiety symptoms than SBFT. Nonspecific therapist variables
      qualified few outcome analyses. No measures of cognitive distortion or family
      dysfunction mediated or moderated treatment outcome. As in adult studies,
      relatively few areas of treatment specificity or mediation were identified. The
      implications of these findings for clinical treatment and research in adolescent
      depression are discussed.

PMID- 10965637
TI  - Prevention of relapse/recurrence in major depression by mindfulness-based
      cognitive therapy.
AB  - This study evaluated mindfulness-based cognitive therapy (MBCT), a group
      intervention designed to train recovered recurrently depressed patients to
      disengage from dysphoria-activated depressogenic thinking that may mediate
      relapse/recurrence. Recovered recurrently depressed patients (n = 145) were
      randomized to continue with treatment as usual or, in addition, to receive MBCT.
      Relapse/recurrence to major depression was assessed over a 60-week study period.
      For patients with 3 or more previous episodes of depression (77% of the sample),
      MBCT significantly reduced risk of relapse/recurrence. For patients with only 2
      previous episodes, MBCT did not reduce relapse/recurrence. MBCT offers a
      promising cost-efficient psychological approach to preventing relapse/recurrence
      in recovered recurrently depressed patients.

PMID- 10965638
TI  - The triple P-positive parenting program: a comparison of enhanced, standard, and
      self-directed behavioral family intervention for parents of children with early
      onset conduct problems.
AB  - Three variants of a behavioral family intervention (BFI) program known as Triple
      P were compared using 305 preschoolers at high risk of developing conduct
      problems. Families were randomly assigned to enhanced BFI (EBFI), standard BFI
      (SBFI), self-directed BFI (SDBFI), or wait list (WL). At postintervention, the 2
      practitioner-assisted conditions were associated with lower levels of parent
      reported disruptive child behavior, lower levels of dysfunctional parenting,
      greater parental competence, and higher consumer satisfaction than the SDBFI and
      WL conditions. Overall, children in EBFI showed greater reliable improvement than
      children in SBFI, SDBFI, and WL. By 1-year follow-up, children in all 3
      conditions achieved similar levels of clinically reliable change in observed
      disruptive behavior. However, the EBFI and SBFI conditions showed greater
      reliable improvement on parent-observed disruptive child behavior.

PMID- 10965639
TI  - Comorbid psychopathology in binge eating disorder: relation to eating disorder
      severity at baseline and following treatment.
AB  - Individuals with binge eating disorder (BED) have high rates of comorbid
      psychopathology, yet little is known about the relation of comorbidity to eating
      disorder features or response to treatment. These issues were examined among 162
      BED patients participating in a psychotherapy trial. Axis I psychopathology was
      not significantly related to baseline eating disorder severity, as measured by
      the Structured Clinical Interview for DSM-III-R (SCID-I and SCID-II) and the
      Eating Disorder Examination. However, presence of Axis II psychopathology was
      significantly related to more severe binge eating and eating disorder
      psychopathology at baseline. Although overall presence of Axis II psychopathology
      did not predict treatment outcome, presence of Cluster B personality disorders
      predicted significantly higher levels of binge eating at 1 year following
      treatment. Results suggest the need to consider Cluster B disorders when
      designing treatments for BED.

PMID- 10965640
TI  - Reducing risk factors for eating disorders: comparison of an Internet- and a
      classroom-delivered psychoeducational program.
AB  - This controlled trial compared Internet- (Student Bodies [SB]) and classroom
      delivered (Body Traps [BT]) psychoeducational interventions for the reduction of
      body dissatisfaction and disordered eating behaviors/attitudes with a control
      condition. Participants were 76 women at a private university who were randomly
      assigned to SB, BT, or a wait-list control (WLC) condition. Measures of body
      image and eating attitudes and behaviors were measured at baseline,
      posttreatment, and 4-month follow-up. At posttreatment, participants in SB had
      significant reductions in weight/shape concerns and disordered eating attitudes
      compared with those in the WLC condition. At follow-up, disordered behaviors were
      also reduced. No significant effects were found between the BT and WLC
      conditions. An Internet-delivered intervention had a significant impact on
      reducing risk factors for eating disorders.

PMID- 10965641
TI  - Testing a typology of batterers.
AB  - A. Holtzworth-Munroe and G. L. Stuart (1994) proposed a tripartite typology of
      men who batter their female partners based on the severity of violence, extent of
      violence, and personality disorder characteristics. The current study attempts to
      empirically validate this typology using data from 75 domestically violent (DV)
      men and their partners, and 32 maritally distressed, nonviolent (DNV) comparison
      couples. Mixture analysis results generally supported the model, although 2 types
      were not distinguishable on personality disorder characteristics as predicted.
      Generally violent batterers were significantly more violent within and outside
      the relationship. The pathological group was moderately violent within and
      outside the relationship and endorsed numerous psychological symptoms. Family
      only batterers endorsed fewer symptoms and were less violent. Violence in the
      family of origin, attachment, and communication skills also differentiated the 3
      types and DNV men.

PMID- 10965642
TI  - Community violence exposure and children's social adjustment in the school peer
      group: the mediating roles of emotion regulation and social cognition.
AB  - This study reports a cross-sectional investigation of the relation between
      community violence exposure and peer group social maladjustment in 285 inner-city
      children in Grades 4-6 (mean age = 10.3 years). Children completed an inventory
      assessing exposure to community violence through witnessing and through direct
      victimization. A peer nomination inventory was then administered to assess social
      adjustment with peers (aggression, peer rejection, and bullying by peers). In
      addition, social-cognitive biases and emotion regulation capacities were examined
      as potential mediators. Analyses indicated that violent victimization was
      associated with negative social outcomes through the mediation of emotion
      dysregulation. Witnessed violence was linked only to aggressive behavior. Social
      information processing, rather than emotion dysregulation, appeared to mediate
      this association. These results demonstrate that violence exposure is linked to
      multiple levels of behavioral and social maladjustment and suggest that there are
      distinct patterns of risk associated with different forms of exposure.

PMID- 10965643
TI  - Adolescent substance abuse treatment outcome: the role of substance abuse problem
      severity, psychosocial, and treatment factors.
AB  - A structural equation model incorporating substance abuse problem severity,
      psychosocial risk and protection, and treatment variables examined adolescent
      drug abuse treatment outcome pathways across 6- and 12-month follow-up points.
      Findings on resiliency factors and an empirical method adapted from previous
      research were used to select and assign 10 psychosocial factors to either a
      multiple protective factor index or a risk factor index. Gender, substance abuse
      problem severity, treatment modality, treatment length, and aftercare
      participation were also examined as outcome predictors. The findings suggest that
      treatment intensity decisions may be better informed by pretreatment psychosocial
      risk level rather than by substance abuse problem severity. The present study
      also suggests that drug-abusing adolescents who receive sufficiently long
      treatment, participate in aftercare, and possess at least 1 individual or
      interpersonal protective factor during their recovery process have the best
      chance to maintain gains made during treatment.

PMID- 10965645
TI  - The Fort Bragg continuum of care for children and adolescents: mental health
      outcomes over 5 years.
AB  - Controversial early results of the Fort Bragg mental-health-effectiveness study
      indicated that the continuum of care did not produce better outcomes (i.e.,
      children's rate of improvement was the same in both the demonstration and
      comparison sites). The present study considered outcomes at 5-year follow-up to
      examine long-term effects from the continuum of care. A random regression
      longitudinal model analyzed 10 key outcome variables measured 7 times. Long-term
      outcomes in continuum-treated children were no better than those of comparison
      children; results are consistent with those of earlier studies.

PMID- 10965644
TI  - Breast cancer surgery: comparing surgical groups and determining individual
      differences in postoperative sexuality and body change stress.
AB  - Women diagnosed and surgically treated for regional breast cancer (N = 190) were
      studied to determine the sexual and body change sequelae for women receiving
      modified radical mastectomy (MRM) with breast reconstruction in comparison with
      the sequelae for women receiving breast-conserving therapy (BCT) or MRM without
      breast reconstruction. The sexuality pattern for women receiving reconstructive
      surgery was one that was significantly different--with lower rates of activity
      and fewer signs of sexual responsiveness--than that for women in either of the
      other groups. Significantly higher levels of traumatic stress and situational
      distress regarding the breast changes were reported by the women receiving an MRM
      in contrast to the women treated with BCT. Using a model to predict sexual
      morbidity, regression analyses revealed that individual differences in sexual
      self-schema were related to both sexual and body change stress outcomes.

PMID- 10965646
TI  - Problem solving in the treatment of childhood obesity.
AB  - This study randomized obese children from 67 families to groups that received a 6
      month family-based behavioral weight-control program plus parent and child
      problem solving, child problem solving, or standard treatment with no additional
      problem solving. The standard group showed larger body mass index (BMI) decreases
      than the parent + child group through 2 years, with significant differences in
      the percentage of children who showed large BMI changes. Significant statistical
      and clinical improvements were observed over time in child behavior problems and
      parental distress. Parent problem solving increased in the parent + child
      condition relative to the other conditions, whereas child problem solving
      increased equally in all conditions. The bulk of evidence suggests that problem
      solving did not add to treatment effectiveness beyond the standard family-based
      treatment.

PMID- 10965647
TI  - A controlled trial of self-help treatment of recurrent headache conducted via the
      Internet.
AB  - The Internet can reach a large number of people at a low cost and offers the
      opportunity for 2-way communication. The present study was designed to evaluate
      the effects of applied relaxation and problem solving in the treatment of
      recurrent headache when implemented via the Internet and E-mail. A group of 102
      headache sufferers were randomized to 2 conditions: a 6-week treatment condition
      or a waiting-list control. The dropout was proportionately large (56%), and at
      the end of the study there were 20 participants in the treatment condition and 25
      participants in the control condition. Results showed statistically significant
      reductions in headache for the treated participants. In 50% of these, the
      reduction was clinically significant. The Internet has the potential to serve as
      a complement in the treatment of recurrent headache and deserves further study.

PMID- 10965648
TI  - Effects of a brief motivational intervention with college student drinkers.
AB  - This study consisted of a randomized controlled trial of a 1-session motivational
      intervention for college student binge drinkers. Sixty students who reported
      binge drinking 2 or more times in the past 30 days were randomly assigned to
      either a no-treatment control or a brief intervention group. The intervention
      provided students with feedback regarding personal consumption, perceived
      drinking norms, alcohol-related problems, situations associated with heavy
      drinking, and alcohol expectancies. At 6-week follow-up, the brief intervention
      group exhibited significant reductions on number of drinks consumed per week,
      number of times drinking alcohol in the past month, and frequency of binge
      drinking in the past month. Estimates of typical student drinking mediated these
      reductions. This study replicates earlier research on the efficacy of brief
      interventions with college students and extends previous work regarding potential
      mechanisms of change.

PMID- 10965649
TI  - [Prediction of improvement of left ventricular wall motion in patients with
      myocardial infarction--by using 99mTc-tetrofosmin and 123I-BMIPP myocardial SPECT
      at subacute phase].
AB  - The relationship between myocardial perfusion, fatty acid metabolism, and cardiac
      functional recovery were investigated by using single photon emission computed
      tomography (SPECT) with 99mTc-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane
      (tetrofosmin: TF) and lodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid
      (BMIPP) in patients with myocardial infarction. We examined myocardial SPECT in
      18 patients with acute myocardial infarction (AMI) underwent successful
      reperfusion therapy within 24 hours from onset. TF myocardial SPECT (early and
      delayed images) and BMIPP (early image) SPECT were performed 2 weeks after onset
      of AMI, and regional TF and BMIPP defect scores of the infarct area were scored
      visually by a 4-point system. There was a significant correlation between the
      defect score of the TF delayed image, BMIPP image and SD/chord (indicator of
      regional wall motion abnormalities on left ventriculograms) at subacute phase
      (TF: r = -0.592, p = 0.011, BMIPP: r = -0.643, p = 0.004). Good correlations were
      also found between the defect score of the TF delayed image, the BMIPP image and
      the SD/chord at chronic phase (TF: r = -0.491, p = 0.037, BMIPP: r = -0.599, p =
      0.007). Furthermore, there was a significant correlation between the improvement
      of SD/chord (acute to chronic phase) and the degree of reverse redistribution
      score of TF (r = 0.735, p = 0.022), and discordance score between TF and BMIPP (r
      = 0.691, p = 0.037). In conclusion, resting BMIPP and TF myocardial SPECT
      performed in patients with subacute phase AMI were shown to be useful in
      predicting improvement of left ventricular function at chronic phase.

PMID- 10965650
TI  - [Successive myocardial fatty acid metabolic imaging in patients with dilated
      cardiomyopathy: usefulness as a prognostic indicator].
AB  - To evaluate the prognostic value of fatty acid metabolic imaging in patients with
      idiopathic dilated cardiomyopathy (DCM), we performed myocardial imaging with
      123I-BMIPP (BMIPP). We studied 23 patients with DCM who were admitted because of
      congestive heart failure (CHF) and after discharge the stable condition persisted
      for more than one year. BMIPP imaging was obtained when CHF recovered (first
      study) and the second study was performed one year after the first study. From
      BMIPP imaging we calculated % Uptake (percentage of cardiac uptake of isotope to
      total injected dose) and Defect Score (degree and extent of regional abnormality
      in BMIPP uptake, DS). In the first study, we performed myocardial imaging with
      201T1 to calculate Uptake Ratio of BMIPP (% Uptake of BMIPP divided by % Uptake
      of 201T1, UR). During the follow up period of 18.2 +/- 9.5 months (4.5-39.6
      months) after the second study, cardiac event developed in 8 patients (cardiac
      death; 4, deterioration of CHF; 4). On univariate analysis, the following indices
      differed significantly between the event and event-free groups; left ventricular
      end-systolic dimension, graded DS, UR and % Uptake of 201T1 at the first study, %
      Uptake of BMIPP and DS at the second study, difference of % Uptake of BMIPP and
      DS between the first and second study, and newly designed index from graded DS of
      the first study and its change in the second study (Defect Index, DI). Cox
      proportional hazard analysis showed that DI (p = 0.0026) and age (p = 0.0262)
      were independent predictors of cardiac events. In patients with DI > or = 3, the
      relative risk of cardiac event was 25.0 times greater than that in patients with
      DI < or = 2. These data suggested that the extent and degree of regional
      abnormality of BMIPP uptake (DS) and its changes with time were useful for
      evaluating the prognosis in patients with DCM even though a clinically stable
      condition is persisting.

PMID- 10965651
TI  - [Difference in 201TlCl accumulation mechanism in brain tumors: a comparison of
      their Na(+)-K+ ATPase activities].
AB  - The accumulation levels of 201TlCl and Na(+)-K+ ATPase activity in tumor tissue
      were compared among glioblastoma, benign glioma and meningioma to study the
      difference in the mechanism of 201TlCl accumulation. The subjects were 19 cases
      comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1
      pilocytic astrocytoma and 9 meningioma. Preoperative 201TlCl SPECT was performed
      in all the cases, and Thallium Index (TL index) was calculated by a ratio of
      201TlCl in the tumor area and the contralateral area. In addition, cell membrane
      was extracted from the tumor tissue collected intraoperatively to determine Na(+)
      K+ ATPase activity. No statistically significant difference in TL index was noted
      between the glioblastoma group (6.97 +/- 2.67) and the meningioma group (5.87 +/-
      1.99). This fact showed that there was no difference in the accumulation level of
      201TlCl between the two groups. On the other hand, the glioblastoma group
      indicated a higher value of Na(+)-K+ ATPase activity (49.13 +/- 43.76
      mumole/hour/mg protein) than the meningioma group (7.73 +/- 13.84 mumole/hour/mg
      protein) (p < 0.05, t test). These results suggested the involvement of Na(+)-K+
      ATPase activity in 201TlCl accumulation in glioblastoma and the influences of
      other accumulation mechanism than Na(+)-K+ ATPase activity such as the volume of
      intratumoral vascular bed in meningioma.

PMID- 10965652
TI  - [Myocardial fatty acid imaging using iodine-123-BMIPP in patients with
      hypertensive intracranial hemorrhage].
AB  - An evaluation of myocardial fatty acid metabolism in hypertensive patients with
      major complication has not been previously established. To assess the myocardial
      fatty acid metabolism in hypertensive patients with intracranial hemorrhage (IH),
      we performed myocardial image using 123I-15-p-iodophenyl-3-methyl pentadecanoic
      acid (BMIPP). Seventeen hypertensive patients with IH (HIH) and 27 hypertensive
      patients without IH (HT) were studied. A dose of 111 MBq of BMIPP was injected
      intravenously at rest, and a myocardial image was recorded 30 minutes after the
      injection. Myocardial perfusion image using Thallium-201 (Tl) was also performed
      within 2 weeks after BMIPP study. The regional myocardial uptakes of BMIPP and Tl
      were visually assessed in 17 segments with a four-point scoring system (0 =
      absent to 3 = normal uptake). Cardiac hypertrophy was evaluated by
      electrocardiography (ECG) and two-dimensional ultrasonic cardiography (UCG). Sum
      of uptake scores of Tl was similar in both groups (45.1 +/- 5.4 vs. 47.9 +/-
      4.2), but that of BMIPP in HIH was lower than HT (35.9 +/- 7.9 vs. 45.6 +/- 4.8,
      p < 0.001). Evaluation of cardiac hypertrophy using ECG and UCG revealed no
      significant difference between two groups. HIH have much more eccentric
      hypertrophy in UCG study than HT (53% vs. 37%). These data suggest that
      hypertensive patients with intracranial hemorrhage have a more impaired
      myocardial fatty acid metabolism compared to the hypertensive patients with
      similar cardiac hypertrophy. BMIPP imaging might be useful to evaluate the
      severity of myocardial fatty acid metabolism in hypertensive patients.

PMID- 10965654
TI  - [Feasibility study of SPECT quantification using CdTe semiconductor detector].
AB  - Quantification of SPECT using CdTe semiconductors as a detector head in nuclear
      medicine equipment was investigated. A prototype of semiconductor detectors with
      an effective field-of-view as small as 2.54 cm x 5.08 cm was constructed, and a
      cylindrical phantom containing four spherical phantoms with capacities 71, 56,
      42, and 15 ml, was used. Water was placed in three of these spherical phantoms
      (71, 56, and 42 ml), and 8.362 MBq of 99mTc was poured into the remaining 15 ml
      phantom. In the outer cylindrical phantom, 925 MBq (6200 ml) of 99mTc was placed.
      A Toshiba LEHR (Low Energy High Resolution) collimator was attached to the
      semiconductor detectors, and SPECT acquisition with a rotation radius 132 mm was
      performed. It was found that in the data thus acquired using the semiconductor
      detector, the amount of scattered gamma-rays decreased by 33% as compared to data
      acquired using NaI(Tl) scintillators under the same condition. Moreover, when
      attenuation correction was applied to SPECT data from the CdTe semiconductor
      detector, the measurement accuracy of radioactivity improved by 16% as compared
      to SPECT data from NaI(Tl) scintillators with the same acquisition and post
      correction conditions. Finally, the CdTe detector data with only attenuation
      correction was found to have almost the same grade of accuracy as NaI
      scintillator data with both attenuation and TEW scatter corrections.

PMID- 10965653
TI  - [Clinical usefulness of 123I-BMIPP myocardial SPECT in collagen disease].
AB  - This study was designed to evaluate the clinical usefulness of 123I-BMIPP
      myocardial SPECT for detecting cardiac involvement in patients with collagen
      disease. We studied 12 patients with systemic lupus erythematosus (SLE), 8 with
      progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM)
      and 3 with allergic granulomatosis and angiitis (AGA). A 111 MBq of 123I-BMIPP
      was intravenously injected at rest, and SPECT images were obtained at 15 min
      after the injection. Seven of 12 SLE, 6 of 8 PSS, 3 of 6 PM/DM and all 3 AGA
      patients showed an abnormal tracer uptake. The left ventricular ejection fraction
      was inversely correlated with a BMIPP abnormality. The regional wall motion
      abnormality was reduced in regions with reduced tracer uptake. These findings
      suggest that 123I-BMIPP imaging could be useful for assessment of cardiac
      involvement in patients with collagen disease.

PMID- 10965655
TI  - [Non-invasive assessment of coronary microvascular function in patients with
      syndrome X using exercise and rest myocardial SPECT with 99mTc-tetrofosmin].
AB  - The purpose of this study was to evaluate impaired coronary microvascular
      function in Syndrome X (Sx) by measuring % uptake increase in myocardial counts.
      Global and regional myocardial uptake was determined with 99mTc-tetrofosmin and a
      4-hour exercise (370 MBq i.v.) and rest (740 MBq i.v.) protocol, in 11 patients
      with anginal syndrome and normal coronary arteriograms (Sx) and in 10 control
      subjects (C). The parameter of % uptake increase (delta MTU) was calculated as
      the ratio of exercise counts to rest myocardial counts with correction of
      myocardial uptake for dose administered and physical decay between the exercise
      study and the rest study. Global delta MTU was significantly lower in Sx than C
      (12.9 +/- 5.4% vs. 22.3 +/- 10.8%, p < 0.05). Regional delta MTU in each of 4
      left ventricular regions (anterior, septal, inferior, posterolateral) was
      significantly lower in Sx than in C (p < 0.05), except for the inferior region.
      However, there were no significant differences between delta MTU in the 4 left
      ventricular regions in the same group. None of the patients with Sx exhibited an
      ischemic pattern in the ST-segment/heart rate loop. delta MTU was useful as a non
      invasive means of evaluating impaired coronary microvascular function in Sx.

PMID- 10965656
TI  - [Seven cases of brain metastasis from papillary thyroid carcinoma].
AB  - Brain metastases from differentiated thyroid carcinoma are extremely rare and
      carry a poor prognosis. We describe here clinical details of 7 cases of brain
      metastases from papillary thyroid carcinoma. Of 153 patients with metastases from
      differentiated thyroid carcinoma (papillary in 123, follicular in 30) treated at
      our institution between 1981 and 1999, 7 patients (4.6%) had brain metastases.
      Histologically, the primary tumor was papillary carcinoma in all 7 cases. Four
      were males and 3 were females. The median age at first diagnosis of distant
      metastases was 63 yr (range, 47-76 yr). Of these patients, one had brain
      metastases only and six had metastases to the lungs as well. Five of these
      patients were treated with 131I. Three of these 5 patients had marked uptake in
      the metastases (131I positive) on post-therapy 131I scans and another 2 patients
      had no significant activity (131I negative) in both pulmonary and brain
      metastatic lesions. One of 3 patients with 131I positive lesions had intense
      activity in the brain tumor, but no uptake in multiple pulmonary metastatic
      tumors. In a patient with 131I positive brain metastases, the tumors progressed
      rapidly after 131I therapy. In another one patient, acute hemorrhage of the tumor
      occurred four days after 131I therapy, requiring surgical removal. Loner case of
      131I negative 2 patients was treated with radiosurgery (gamma-knife) and complete
      reduction in tumor volume was observed. On the other hand, one of 2 patients
      receiving no 131I therapy had radiosurgery (x-knife) and remaining one received
      conventional external radiation and chemotherapy for small solitary brain and
      pulmonary metastatic tumors. These therapeutic interventions were useful in both
      cases. The mean length of survival after the development of brain metastases in
      the five patients who died of the disease was 30 months. One patient treated with
      x-knife has been alive at 21 months and another one who has 131I uptake in the
      brain tumor without uptake in lung lesions has been alive 15 months after
      diagnosis of brain metastasis. These results indicate that it is important to
      detect brain metastasis by imaging techniques and Tg measurements and give
      treatment as early as possible since the brain is the third most common distant
      metastatic site and the prognosis is poor.

PMID- 10965657
TI  - [Correlation of pulmonary perfusion volume analysis with pulmonary function in
      emphysema].
AB  - Pulmonary perfusion single photon emission tomography with 99mTc MAA was
      performed on 13 pulmonary emphysema patients and 6 controls. We calculated
      perfusion volume with lower 10%, 20%, 30%, 40% and 50% of the highest
      counts/boxels in the lung cut-off. And perfusion index (PI) was defined as
      follows; PI = ((A% cut-off volume) - (B% cut-off volume))/(A% cut-off volume); A
      and B take 10 to 50, A < B. The correlation of each PI and pulmonary function
      test results (FEV1, FEV1%, VC, VC%, FVC, FVC%, PaO2 and PaCO2) was examined.
      There were significant correlation between every PI and FEV1 or FEV1% (p < 0.05),
      and any PI had no significant correlation with other functional results. When A =
      10 and B = 40, the PI showed the best correlation with FEV1 (r = 0.680) and FEV1%
      (r = 0.830). And the PI showed an increasing tendency along with the rise of the
      emphysema severity. The PI may have the clinical utility of the evaluation of
      pulmonary function. Moreover, we showed the lung CT painted the area where the
      uptake counts/boxels was more than 10% and less than 40% of the highest
      counts/boxels. This makes it easy to understand the severe emphysematous area.

PMID- 10965658
TI  - [Evaluation of serological response to Bartonella henselae by enzyme immunoassay
      in cat scratch disease].
AB  - The IgG and IgM titers to Bartonella henselae were determined by an enzyme
      immunoassay (EIA). The EIA test for detection of IgG and IgM antibodies to B.
      henselae concerning CSD showed that 8 (40%) of 20 patients with CSD had a serum
      IgG antibody titer of 12 EIA unit or more and that 5 (25%) patients had a serum
      IgM titer of 12 EIA unit or more. Totally 12 (60%) of the 20 patients with CSD
      were seropositive for B. henselae. The mean age of IgG positive patients were
      higher than IgM positive patients. The IgM antibodies to B. henselae disappeared
      within 4 to 12 weeks after onset of disease. The IgG antibodies to B. henselae
      disappeared within 3 to 8 weeks after onset of the symptoms in 2 cases of CSD.
      Another 2 cases CSD produced high levels of IgG antibodies in the acute phase of
      the disease. Different course of IgG and IgM antibody titers were found in sera
      from patients.

PMID- 10965659
TI  - [Probe types of Norwalk-like viruses genome detected by RT-PCR with seven primer
      pairs in Yamanashi Prefecture].
AB  - The reverse transcription-polymerase chain reaction (RT-PCR) gene assay, as well
      as electron microscopic examination, is commonly used to detect Norwalk-like
      viruses (NLVs). Types and number of primer pairs used are considered to be of
      critical importance for efficiency of the RT-PCR detection. This study was
      performed to determine primer pairs useful for the detection of NLVs. NLVs genes
      were detected by RT-PCR in 48 cases in Yamanashi Prefecture between December 1997
      and March 2000. The probe type of the gene was G2P-C in 21, G2P-B in 10, G2P-A in
      6, G1P-A in 3, G1P-B in 2, and a mixture of G2P-A and G2P-B in 6. The NLVs genes
      of G2P-C and G2P-B were estimated to have undergone mutation in the polymerase
      region and poorly specific to the primer pair 35/36, a combination that has been
      used most commonly for the RT-PCR assay in Japan. The primer pair G2R1/F1 that
      amplifies the capsid (CAP) region of NLVs genes can detect all NLVs genes of the
      Genogroup2. The combination of this primer pair with another primer pair G1R1/F1,
      which like G2R1/F1, amplifies the CAP region, makes discrimination between NLVs
      of different groups possible. Consequently, this combination, may be the most
      useful for the NLVs detection by RT-PCR.

PMID- 10965660
TI  - [A new exanthematous disease in newborn infants caused by exotoxins producing
      methicillin-resistant Staphylococcus aureus; pathology from viewpoints of local
      and systemic levels of exotoxin and cytokine].
AB  - Neonatal exanthematous diseases induced by toxic shock syndrome toxin-1 (TSST-1)
      producing methicillin-resistant Staphyloccocus aureus (MRSA) is one of emerging
      infectious diseases in Japan. We experienced 36 patients with this disease in
      National Kagawa Children's Hospital and in 13 patients of them, investigated the
      role of both the toxin and cytokines in pathogenesis of it. The results are
      summarized as follows: 1. The TSST-1 level was high in the umbilical inflammatory
      exudate of cases induced by umbilical infection and in the gastric fluid of cases
      induced by respiratory infection. The blood TSST-1 level was below the detection
      limit in most of the exathematous++ cases examined, but it was detected in one of
      the nine cases induced by respiratory infection and a case secondary to severe
      MRSA infection (phlegmonous abscess in buttock). 2. Local cytokine levels were
      examined in the abscess pus obtained from a case of severe MRSA infection and in
      the gastric fluid from cases induced by respiratory infection. The local levels
      of TNF [alpha], IL-1 [beta], IL-6 and IL-8 were markedly high, but the local
      levels of IL-2 and IFN-[gamma] were similar to their blood levels. 3. The
      severity of hypercytokinemia (IL-1 [beta], IL-2, IL-6, IFN-[gamma]) was
      proportionate to the severity of exanthematous disease. Accompanied by increased
      levels of inhibitory factors sTNF-R, IL-1 ra, sIL-2R and IL-10, this
      hypercytokinemia normalized soon within four or five days. 4. As compared to
      cases induced by umbilical infection, cases induced by respiratory infection
      often had higher blood cytokine levels and some of them had cardiorespiratory
      disorders. Based on the results of this study, we consider that this disease is
      generally induced by toxemia with a small number of toxins without tissue
      destructive lesions by MRSA infection and that this is closely related to the
      course of the disease that shows a tendency to a spontaneous recovery.

PMID- 10965661
TI  - [An imported case of primary pulmonary coccidioidomycosis].
AB  - Coccidioides immitis is a causative agent of coccidioidomycosis, which is one of
      the most dreadful mycosis because of its infectious and pathogenic nature. The
      endemic areas are in the southwestern parts of the United States and other semi
      arid regions throughout the Western Hemisphere. During the early 1990s, the
      incidence of coccidioidomycosis in California increased dramatically, resulting
      in recognition for this mycosis as a reemerging infectious disease in the United
      States. The patients included a large number of non-informed visitors from non
      endemic countries. Our report is on an imported case of primary pulmonary
      coccidioidomycosis. A 35-year-old Japanese male, after living in the United
      States for nine months, suffered from a combination of headache and fever. He was
      given a serological examination, and a chest radiograph in Phoenix, Arizona in
      the United States and was diagnosed as coccidioidomycosis. A daily dosage of 400
      mg of fluconazole was administered and he returned to Japan. His headache and
      skin rash persisted and he was admitted to our hospital to evaluate the severity
      of his disease. There were no fungi cultured from neither bronchoalveolar nor
      cerebrospinal fluid and he was discharged. The patient had been treated with
      fluconazole and his symptoms, high-resolution CT and serological antibody titer
      were monitored. After 18 months, his clinical and radiological evolution was
      favorable and his serological IgM titer was below its sensitivity medication was
      stopped and there were no relapses.

PMID- 10965662
TI  - [A recurrent case of amebic liver abscess seventeen years after the first
      occurrence].
AB  - A 49-year-old male who had been diagnosed as having amebic liver abscess when he
      was 32-year-old was admitted to our hospital with fever and watery diarrhea.
      Ultrasonography and CT examination demonstrated a solitary abscess in the right
      lobe of the liver. Cysts of Entamoeba histolytica were detected in the stool and
      an aspiration of the liver abscess looked like anchovy paste. Serum amebic
      antibody by the IFA method was positive and the case was diagnosed as amebic
      liver abscess. The patient was treated with metronidazole, and percutaneous
      transhepatic abscess drainage was performed. The liver abscess decreased
      remarkably in size and serum amebic antibody was negative after the treatment.
      Recurrence of amebic liver abscess is rare and we report this case with some
      literature.

PMID- 10965664
TI  - [A case report of lung abscess caused by Capnocytophaga gingivalis infection].
AB  - A 48-year-old male was admitted to our hospital because of fever, cough and of
      loss appetite. Chest X-P revealed an abnormal shadow in the left upper lobe.
      Bronchoscopy was performed and Capnocytophaga gingivalis was cultured from the
      bronchial lavage and bronchial curreting fluid. Ceftizoxime sodium and
      Clindamycin phosphate was administered intravenously. He was discharged after 30
      days. He did not have any immunosuppressive underlying disease including HIV
      infection and diabetes mellitus which cause these lesions.

PMID- 10965665
TI  - [Cytokine modulation induced by minocycline in Tsutsugamushi disease].

PMID- 10965663
TI  - [A case of tuberculous peritonitis diagnosed by ultrasonography-guide peritoneal
      biopsy].
AB  - The diagnosis of tuberculous peritonitis is quite difficult because the symptoms
      are not specific for the disease and the incidence of occurrence are relatively
      rare. We report a case of tuberculous peritonitis diagnosed by ultrasonography
      guided peritoneal biopsy. A 64-year-old male was admitted to our hospital because
      of fever, dyspnea and abdominal pain. Laboratory findings revealed an elevated
      ESR (53 mm/1 hr.) and positive CRP. The tuberculin skin test was negative. The
      chest radiograph revealed bilateral pleural effusion. Abdominal ultrasonographic
      examination and computed tomography showed ascitic fluid, thickening of the
      mesentery and peritoneum, and inflammatory pseudotumor of the omentum. Ascitic
      fluid was exudate with a high lymphocyte count and elevated ADA (184 IU/l).
      Microbiological studies with the fluid were negative. Peritoneal biopsy guided by
      ultrasonography was performed, and the specimens showed central caseous necrosis
      surrounded by epitheloid cells and acid-fast bacilli were demonstrated. The size
      of the pseudotumor, pleural effusion and ascites decreased after antituberculous
      chemotherapy with corticosteroid was given. Diagnosis of tuberculous peritonitis
      has often been made by laparotomy or laparoscopy. In a case of this kind,
      percutaneous peritoneal biopsy guided by ultrasonography is safe and useful.

PMID- 10965666
TI  - [In vitro susceptibilities of Helicobacter pylori strains from children to proton
      pump inhibitors and its thioether derivative].

PMID- 10965667
TI  - [Dermal risk assessment in occupational medicine].
AB  - The importance of dermal exposure has increased during the last few years mainly
      because of the reduction of respiratory exposure to toxicants. Pesticides,
      aromatic amines and polycyclic aromatic hydrocarbons are considered to be the
      chemicals with highest dermal risk. In the occupational exposure limit lists of
      the ACGIH and of many countries compounds that can be absorbed through the skin
      are identified by a skin notation. Usually the skin notation indicates that the
      percutaneous absorption of the chemical can contribute to the body burden.
      However, a generally accepted criterion for assigning skin notation does not
      exist. When it is possible to make standardized measurements of dermal exposure,
      it will be possible to develop Dermal Occupational Exposure Limits (DOEL) with
      which such measurements can be compared to enable a regulatory approach in the
      risk assessment field. However, the recent attempts to develop health-based DOELs
      have not been accepted, thus in practice their use has been limited.

PMID- 10965668
TI  - [Assessment of occupational exposure to aromatic polycyclic hydrocarbons
      determining urinary levels of 1-pyrenol].
AB  - In conformity with Italian law 626/94, occupational exposure to Polycyclic
      Aromatic Hydrocarbons (PAH) in several types of work environments was assessed by
      analysing urinary levels of 1-pyrenol. A total of 231 non-smokers exposed to PAH
      (82 workers, employed in two different thermoelectric power plants using
      combustible oil (30 subjects from plant A and 52 from plant B), 18 subjects
      working for a company recovering exhausted oils, 12 working on rubber production,
      10 on road surface asphalting operations, 22 working in the anodizing section of
      an aluminium plant, 27 chimney-sweeps, and 60 coke-oven workers (30 topside
      workers, and 30 doing other jobs)) were enrolled. There were also 53 non-smoker
      control subjects, not occupationally exposed to PAH. Current smokers were
      excluded, since smoking is an important confounding factor when occupational
      exposure to low PAH concentrations are monitored. Confounding factors, i.e., diet
      and passive smoking, were checked by means of a questionnaire which, in addition
      to personal data and habits, also requested specific details about the type of
      diet followed and possible exposure to passive smoking during the 24-hour period
      preceding urine collection. In controls, exposure to PAH in the diet
      significantly increased 1-pyrenol levels in urine: in subjects introducing > or =
      1 microgram of pyrene with the diet, the mean urinary level of 1-pyrenol was
      significantly higher than that introduced with < 1 microgram (high versus low
      dietary intake, mean +/- SD, 0.08 +/- 0.13 and 0.04 +/- 0.06 1-pyrenol
      mumoles/mole of creatinine, respectively; Mann-Whitney U-test Z = 2.67, p <
      0.01). Conversely, passive smoking did not influence 1-pyrenol levels. In the
      overall population (controls and exposed), multiple linear regression analysis
      showed that levels of urinary 1-pyrenol were significantly influenced by
      occupational exposure to PAH in asphalt workers, anodizing plant workers, chimney
      sweeps, and coke-oven workers, both those working at the top side of the oven and
      those doing other jobs (t = 2.19, p = 0.02; t = 2.56, p = 0.01; t = 5.25, p =
      0.001; t = 3.34, p = 0.001; t = 7.82, p = 0.001, respectively; F = 9.7, p <
      0.01), but not in power plant workers in contact with combustible oils, workers
      recovering exhausted oils, or rubber production workers. Diet and passive smoking
      did not influence urinary 1-pyrenol levels in the entire sample population. This
      biomarker also allowed an assessment of exposure levels among certainly exposed
      subjects. The percentage of subjects with urinary 1-pyrenol values higher than
      the 99th percentile of the reference population (0.67 mumoles 1-pyrenol/mole of
      creatinine) was significantly higher than that of controls in asphalt workers
      (20%), anodizing plant workers (14%), chimney-sweeps (13%) and coke-oven workers
      (33%) (chi-square test: asphalt workers = 6.1, p = 0.01; anodizing plant workers
      = 4.3, p = 0.04; chimney-sweeps = 7.1, p = 0.008; coke-oven workers with other
      duties = 4.4, p = 0.04; top side workers = 16.5, p < 0.001). In chimney sweeps
      and top side workers, respectively 2 and 4 subjects (7% and 13%) exceeded the
      precautionary level of 1.4 mumoles 1-pyrenol/mole of creatinine; of these, 1
      chimney sweep and 3 top side workers (4% and 10%) exceeded the recommended
      biological threshold of 2.3 mumoles 1-pyrenol/mole of creatinine.

PMID- 10965669
TI  - Prevalence of self-reported health complaints among shoe workers of small
      workshop exposed to organic solvents in Hebron City, West Bank: a cross-sectional
      survey.
AB  - The study was conducted to estimate the prevalences of neurological disorders and
      mucous membrane irritation complaints among workers of shoe workshops in Hebron
      City, in particular to measure the associations between the occurrence of
      symptoms indicating polyneuropathy among workers and exposure to organic solvents
      in the glueing tasks. A group of 103 male workers from 30 workshops, exposed to
      organic solvents for more than one year were recruited to the study during the
      years 1996-1997. A validated Swedish neuropsychiatric questionnaire which
      contained questions on neurological and mucous irritation symptoms was used.
      Prevalence ratios were used as an indicator for relative risk. The overall
      prevalence of painful tingling of limbs (used as indicator of polyneuropathy) was
      high among the workshop workers (40%) and was significantly associated with long
      term exposure to organic solvents in glueing tasks (PR 2.8: 95% CI 1.0-8.3).
      Moderate associations were seen in other tasks. Headache and mental irritability
      did not show any association with organic solvent exposure in the workshop tasks.
      Breathing difficulty showed a moderate non-significant association with long term
      exposure to organic solvents (72 months) in cleaning tasks (1.9,0.7-4.8), while
      sore eyes also showed a moderate non-significant association with exposure to
      organic solvents for 25-72 months in the glueing tasks. Long term exposure to n
      hexane (mainly found in the glues) could be the main cause of polyneuropathy
      among the workers of Hebron shoe workshops. The absence of effective ventilation
      systems and personal protective equipment might increase the prevalence of
      polyneuropathy among these workers. In conclusion, glues containing high
      concentrations of n-hexane are still in use in many shoe workshops in Hebron City
      (as well as in other developing countries), and long term exposure to n-hexane in
      glueing compounds could result in polyneuropathy among the workers. However, in
      the absence of objective measurements our results must be interpreted with
      caution. Well planned longitudinal studies with objective measures of exposure
      and disease are important for future research in developing countries.

PMID- 10965670
TI  - [Neuropathies caused by vibrating instruments: clinico-diagnostic study of a
      group of symptomatic subjects].
AB  - In order to evaluate the risk connected with hand-arm vibration exposure and
      associated disorders of the peripheral nervous system a study was made to assess
      the relationship between nervous symptoms and laboratory data to determine the
      kind of disorder. 40 male subjects with hand-arm vibration exposure for more than
      5 years and nervous symptoms of the hands for more than 1 year and 2 control
      groups of non-symptomatic non-exposed subjects were considered. An
      electroneurophysiological study of the exposed subjects revealed 18 nerve
      conduction speed changes (12 median nerve, 4 ulnar nerve, 2 median and ulnar
      nerve), most of which were sensitivity-motor changes; only 9 Carpal Tunnel
      Syndromes were diagnosed. Some statistically significant differences between
      exposed subjects with negative results of the electroneurophysiological study and
      non-exposed subjects were observed. Prolonged vibration exposure seems to induce
      a hand-arm nerve suffering, initially with a progressive nerve conduction speed
      change and non-specific symptoms, but subsequently a peripheral nervous system
      disorder associated or not to a Carpal Tunnel Syndrome may occur.

PMID- 10965671
TI  - [Vaccine prophylaxis: contribution for the control of biologic risk in exposed
      workers].
AB  - Working activities with exposure to biological agents have become a matter of
      discussion especially after the introduction in Italy of the Law 626/94, in
      conformity with the EU directive 90/679/EEC. There are many important biological
      agents that can have infectious, allergic, toxic or carcinogenic effects on the
      working population. Large occupational groups are exposed to these biohazards,
      both in agriculture and industry. Vaccination is one of the most beneficial
      medical practices, which has led to the eradication of such a devastating human
      disease as smallpox and the almost total elimination of poliomyelitis.
      Vaccination is also one of the most cost effective prevention measures applicable
      in this respect. This paper describes the possible vaccinations that employers
      should make available to employees exposed to biological risk, according to
      article 86 of Law 626/94.

PMID- 10965672
TI  - [Neoformed multiple hepatic angiomas after exposure to vinyl chloride monomer:
      report of a case].
AB  - The paper describes the case of a 60 years old man with previous protracted
      exposure to CVM. After a latency of 20 years, the man developed two hepatic
      hemangiomas, one characterized by rapid growth (4 cm of diameter in 1 year) and
      surgically removed. On the basis of the anamnestic data (15 years in a PVC
      polymerization factory in the reactor vessels department) considering the degree
      and duration of exposure to CVM, an occupational origin of the hepatic
      hemangiomas is probable. The ability of CVM to induce sclerosis, necrosis and
      endothelial hyperplasy in the liver tissue may represent the primum movens of
      hemangiomas.

PMID- 10965673
TI  - [Contribution to the discussion started by P. Apostoli "A Century of Occupational
      Medicine in Italy: opportunity for a debate for revamping the discipline" (Med
      Lav 1999; 90: 808-812)].

PMID- 10965674
TI  - [Biological risk or social support?].

PMID- 10965675
TI  - Doctors and smoking.
AB  - The objective of this paper is to present cigarette smoking as the greatest risk
      factor for premature death, the nature of smoking dependence, the methods for its
      cessation, and to establish the importance of the leadership of health care
      providers in smoking prevention. Because smoking as a risk factor is preventable,
      it is necessary to conduct rigorous preventive measures, including educational
      programs and various legal actions, such as restrictions on the purchase of
      tobacco products to teenagers and creation of smoke-free areas. Reduction in the
      prevalence of smoking among physicians and other health care professionals also
      significantly influences willingness of society to recognize the health
      consequences of smoking and perhaps lead to the decline of the smoking epidemic.
      Therefore, a special attempt should be made to reduce smoking among health
      professionals, including medical students. An effort of medical students in
      Yugoslavia to promote prevention of smoking in the public by introducing "January
      31st--A Day Without a Cigarette" is described. The best way to discourage smoking
      is by approaching children and adolescents since most people start smoking in
      their teenage years. This age group must recognize the harmful effects of
      smoking. Banning advertising and other promotional activities of tobacco
      producers, as well as smoking in hospitals, workplaces, restaurants, and public
      transportation is a very strong weapon against smoking.

PMID- 10965676
TI  - [Effect of non-medical factors on drug utilization in perinatal hospital
      practice].
AB  - INTRODUCTION: Beside medical, nonmedical factors also influence the quantity and
      structure of administered drugs. Therefore, it is of importance to analyze these
      factors and their influence on drug consumption in perinatological hospital
      practice. The aim of this study was to analyze pharmacotherapeutic practice as
      well as the influence of nonmedical factors on drug use at the Institute of
      Perinatology of the Department of Obstetrics and Gynaecology in Novi Sad.
      MATERIAL AND METHODS: The study was of retrospective-prospective character.
      Analyses comprised drug consumption for the period 1989 and the first 6 months of
      1993 and 1994 analyzing data obtained from the hospital pharmacy. Due to lack of
      drug supply in the hospital pharmacy and domestic market, a sample of 10%
      patient's histories were taken for analysis in order to compare the above data
      for the same time interval. All drugs were classified according to the unique ATC
      (Anatomical Therapeutic Chemical) classification, where the Defined Daily Dose
      (DDD) was taken as the drug use statistical unit. RESULTS AND DISCUSSION:
      According to the data from the hospital pharmacy, the total drug consumption in
      1989 was 7301,85 DDD/BD and in 1993 and 1994 it was significantly decreased (1993
      -5135,80 DDD/1000 BD vs. 1994--2095,90 DDD/1000 BD). Majority of drugs for all
      the investigated periods were administered for the group G (urogenital system and
      sex hormones) out of which most often used drugs were G02A (drugs for stimulation
      of uterine contractions). According to the patients' history data, drug use was
      significantly increased in 1993--6322,22 DDD/1000 BD and 1994--3340,01 DDD/1000
      BD. The only exception was group A (alimentary tract and metabolism) in which,
      according to history data, drugs were significantly less frequently prescribed
      than supplied. The greatest difference in the quantity of prescribed drugs
      (patients' history data) and the drugs issued from the hospital pharmacy was
      recorded in the group C (cardiovascular system), G (urogenital system and sex
      hormones) and H (hormones for systemic use with sex hormones excluded).
      Prescription of drugs from the groups C and H respectively, according to history
      data was most probably justified, but a question is raised concerning high rate
      of drug prescription in group G.

PMID- 10965677
TI  - [Coronary collateral circulation and prevention of ischemic mitral
      regurgitation].
AB  - INTRODUCTION: According to definition, collateral circulation is an alternative
      to major vascular flow which has become dysfunctional. Collateral channels,
      initially unused, are being formed due to impossibility of the main blood vessel
      to provide normal coronary flow. Recent controversies about collateral
      circulation are mainly based on their functional significance. The aim of this
      work was to evaluate the function of collateral circulation in patients after the
      first postero-inferior myocardial infarction i.e. whether adequate collateral
      circulation may reduce the size of myocardial infarction and prevent development
      of ischemic mitral regurgitation. MATERIAL AND METHODS: The investigation
      included 128 patients (pts) treated at the Institute of Cardiovascular Diseases
      in Sremska Kamenica during 1997 and 1998. The investigation group (I) included 64
      pts, 58 males and 6 females, mean age 54.42 years. The control group (C) included
      64 pts, 56 males and 8 females mean age 51.71 years. In all patients the first
      posterior, inferior and postero-inferior myocardial infarction were proven during
      1-year period. Cineventriculography confirmed kinetic disturbance of the area
      with or without mitral insufficiency. Degree of mitral regurgitation was
      evaluated according to Seller's criterion. Alterations on the right coronary or
      circumflex branch of the left coronary artery were confirmed, but significant
      stenotic alterations were not verified on the anterior descendent branch of the
      left coronary artery. Alterations on epicardiac coronary vessels were presented
      as total coronary score--modification according to Benc (18 segments) while
      numerical values for stenosis according to Kaltenbach. This value represents the
      total coronary score (SCORE-A) including alterations before and after occlusion.
      Gensiny's principle modified for multiplication factor according to Benc and
      numerical value according to Kaltenbach were used for evaluation of collateral
      circulation. Levin's classification was used for evaluation of collateral
      circulation quality. We used quantitative classification according to Cohen.
      RESULTS: Distribution of mitral regurgitation was not statistically and
      significantly frequent in the subgroup of patients with lesions on the right
      coronary artery in relation to subgroup of patients with combined lesions on the
      right coronary artery and circumflex branch of the left coronary artery (p >
      0.05). None of the investigated patients with extensive lesions (lesions on ACD
      and RCX) had mitral regurgitation of IV degree, so the number of investigated
      patients was not adequate for statistical evaluation. We did not find a
      statistically significant difference in the percentage of collateral circulation
      between the investigation (59.4%) and control group (62.5%) (p > 0.05). Poorly
      developed collaterals were statistically and significantly more frequent in the
      investigation group (60.5%) in relation to control group (10%) (p < 0.01). The
      percentage of moderately developed collateral circulation was similar in both
      groups. Well developed collateral circulation was statistically and significantly
      more frequent in control group (52.5%) in relation to investigation group (7.9%)
      (p < 0.01). The extension of stenotic alterations expressed as total coronary
      score A was statistically and significantly higher in subgroups of investigated
      patients with combined alterations on ACD and RCx, proving the sensitivity of our
      score system in smaller extensity of stenotic lesions on epicardial coronary
      blood vessels. Collateral circulation was significantly better in patients with
      ACD occlusion (100%) in relation to patients with significant stenosis or ACD
      subocclusion (33.3%) (p < 0.01). DISCUSSION: The functional role of collaterals
      has not been explained yet. The efficacy of coronary collateral vessels and
      mechanism of adequate compensation of regional perfusion in a position distal
      from the occluded vessel is highly controversial. (ABSTRACT TRUNCATED)

PMID- 10965678
TI  - [Skin diseases and hepatitis virus C infection].
AB  - INTRODUCTION: Using a creative molecularbiologic technique in 1989 Choo and co
      workers isolated a new virus of hepatitis C, an agent responsible for numerous
      cases of parenterally transmissible viral hepatitis. Hepatitis C virus is a RNA
      virus with unique genomic organisation. Six genotypes of hepatitis C virus have
      been identified, which differ in geographical distribution, tendency towards
      chronicity and sensitivity to antiviral therapy. Transmission occurs due to
      apparent and inapparent parenteral procedures (after transfusion,
      transplantation, transplacentally, during lactation, sexually or after accidental
      injury of medical staff). Mode of transmission through intact skin or mucosa has
      not been proved yet. Due to development of laboratory methods for detection of
      anti-hepatitis C virus antibodies and obligation for routine testing of blood
      donors for hepatitis C in majority of countries in the world, risk of post
      transfusion hepatitis C is minimised to less than 1%. In 70% of patients the
      infection runs a chronic course, affecting numerous extrahepatic organ systems,
      including skin. VASCULITIS ASSOCIATED WITH MIXED ESSENTIAL CRYOGLOBULINEMIA:
      Mixed essential cryoglobulinemia is a disorder with deposition of circulating
      immune complexes in small and medium blood vessels. Clinical characteristics
      comprise palpable purpura on lower extremities, arthralgias and weakness. It
      might occur during autoimmune disorders, liver diseases and viral infections,
      among which hepatitis C infection has a central part. Mixed cryoglobulins can be
      detected in 35-54% of patients with hepatitis C and symptomatic vasculitis
      associated cryoglobulinemia, decreased C4 component of complement, positive
      rheumatoid factor and elevation of hepatic enzymes occurs in 10-21% of patients.
      Findings of anti-hepatic C virus antibodies and/or viral RNA in 96% of patients
      with mixed cryoglobulinemia can be considered as a definitive proof of
      etiopathogenetic association between hepatitis C infection and mixed
      cryoglobulinemia. Interferon alpha therapy is a first-choice therapy, although
      transient responses are frequent. PORPHYRIA CUTANEA TARDA: Hepatitis C infection
      has recently been recognised as an important precipitating factor of clinical
      porphyria cutanea tarda sympotomatology. Apart from high level of seropositivity
      among porphyria cutanea tarda patients (62-100%), association between these two
      entities hasn't been clearly revealed yet. The question whether hepatitis C
      infection is enough to be the only precipitating factor, or other hepatotoxic
      cofactors are necessary, still exits. Interferon therapy has been a meter of
      several studies, but no definite recommendations had been given about its
      administration in these cases. LICHEN PLANUS: About possible association between
      lichen planus and chronic liver diseases, and hepatitis C infection as well,
      suggest 35% prevalence of hepatic disorders in patients with lichen planus, and
      9.8-23% of hepatitis C virus seropositivity. The clinical picture of lichen
      planus in hepatitis C virus infection is characterised by generalised skin
      lesions, with erosive involvement of oral mucous membrane, and by chronic course.
      Therapeutical efficiency of interferon is unpredictable, with possible
      improvement, cure or deterioration of lichen planus. OTHER DERMATOLOGICAL
      DISORDERS: Other dermatological disorders (erythema nodosum, erythema multiforme,
      urticaria) may be direct consequences of hepatitis C infection, of other
      extrahepaic non-dermatological manifestations, or fortuitous reports. CONCLUSION:
      Considering big pathogenetic potentials of hepatitis C virus with possible skin
      involvement, and proved association between cutaneous necrotising vasculitis with
      mixed essential cryoglobulinemia, porphyria cutanea tarda, lichen planus and
      chronic hepatitis C infection, all patients with these disorders should be tested
      for hepatitis C and all cases of hepatitis C should be searched for signs and
      symptoms of these skin diseases.

PMID- 10965679
TI  - [Reversible dysfunction of the left ventricle in coronary disease (part two):
      hibernation and methods for detection of viability].
AB  - HIBERNATION: Hibernating myocardium is defined as a state of persistently
      impaired myocardial function, as a consequence of reduced coronary flow, which
      can be partially or completely reversed if the myocardial oxygen
      consumption/demand ratio is favorably altered. Since it indicates concordance
      between flow and function (flow-function relation), it can be concluded that
      hibernating myocardium, caused by reduced myocardial perfusion, improves its
      function after surgical revascularization, giving its detection a great clinical
      importance. Hibernating myocardium can be found in majority of patients with
      coronary artery disease and chronic left ventricular dysfunction. These patients,
      even without typical symptoms of angina, will benefit from myocardial
      revascularization. This beneficial effect is expressed by ejection fraction
      enhancement, which is directly proportional to the number of dysfunctional, but
      viable segments. Also, symptom improvement depends on the mass of revascularized
      myocardium, which is previously shown to be viable. Having that in mind, the mass
      of viable myocardium must be large enough, so that the degree of expected
      improvement of myocardial function after revascularization justifies the
      operation itself. Opposing this classical concept of hibernating myocardium,
      recent studies have shown that in patients with coronary artery disease, coronary
      flow at rest is normal or just slightly reduced, which cannot explain the degree
      of myocardial dysfunction. According to that, it is proposed that myocardial
      dysfunction is, like in myocardial stunning, the result of flow-function
      mismatch, meaning that pathophysiology of hibernating myocardium includes a
      component of stunning as well. Therefore, hibernating myocardium can be defined
      as a form of reversible left ventricular dysfunction, caused by chronic coronary
      artery disease, which is partially due to episodes of repetitive stunning and
      shows improvement after inotropic stimulation. From practical point of view, it
      is important to detect hibernating myocardium in all patients with coronary
      artery disease and left ventricular dysfunction, since their treatment and
      prognosis directly depend on whether the dysfunction is reversible or not.
      METHODS FOR IDENTIFICATION OF MYOCARDIAL VIABILITY: Detection of myocardial
      viability has great clinical importance, since both regional and global left
      ventricular function can significantly improve, either spontaneously or by
      myocardial revascularization. Noninvasive imaging procedures used for that
      purpose include positron emission tomography, thallium-201 imaging, technetium-99
      imaging, dobutamine echocardiography and tissue characterization. Using these
      methods, it is possible to assess the presence of viable tissue through
      evaluation of metabolic activity, integrity of myocyte membrane and the inotropic
      reserve of myocardium.

PMID- 10965680
TI  - [Influenza--always present among us].
AB  - INTRODUCTION: Influenza virus infects about 10 million persons worldwide each
      year. Two important characteristics of influenza are its epidemic outbreak and
      high mortality rate, mostly caused by complications. Influenza virus is
      characterised by a great antigenic variability. Major modifications, called
      antigenic shifts or type changes, occur approximately three times per century and
      result in worldwide epidemics--pandemics. Minor modifications, called antigenic
      drifts or strain changes demand new vaccine compositions each year. HISTORY:
      Pandemics and epidemics caused by influenza virus, such as the "Spanish Flu", the
      "Asian Flu", the "Hong Kong Flu" killed many people worldwide. Presently the
      epidemic, caused by influenza A virus Sydney/97 H3N2 is spreading over USA and
      most of Europe, including Yugoslavia. EPIDEMIOLOGY AND CLINICAL FEATURES: In
      humans influenza virus spreads over respiratory secretions, thrown out by
      coughing and sneezing. Children and older people, as well as immunosuppressed
      patients are prone to the infection. The onset of illness is sudden, with fever
      usually over 39 degrees C. Headache and myalgia are prominent. Other signs
      include fatigue, sore throat, nasal congestion and red eyes. Cough is a very
      important symptom, which starts as dry and progresses to wet with thick mucous.
      COMPLICATIONS: Pneumonia is the main cause of death among the high-risk patients.
      Bronchitis and tracheobronchitis also occur. Croup is a serious complication,
      often encountered in small children. Cardiac complications, especially
      myocarditis, are described as influenza complications. Neurological complications
      include encephalitis, encephalopathy, myelitis, Guillain-Barre syndrome, Reye
      syndrome, etc. Neurotropism of the influenza virus is under investigation.
      DIFFERENTIAL DIAGNOSIS AND DIAGNOSIS: Differential diagnosis of influenza
      includes all diseases which exhibit by increased body temperature, cough,
      headache, sore throat, myalgia and lethargy. Among serious diseases, pneumonia,
      sepsis, and meningitis should be considered. Various tests are used when
      diagnosing influenza: antigen detection, polymerase chain reaction,
      immunofluorescent tests, etc. THERAPY: Treatment of influenza by antiviral drugs
      can be prophylactic and therapeutic. Amantadine and rimantadine are older drugs
      effective in cases caused by virus type A. The newest generation of influenza
      antiviral agents are neuraminidase inhibitors--zanamivir and oseltamivir,
      effective against both virus types. The symptomatic therapy is still a basis of
      influenza treatment. PREVENTION: The main means of influenza prevention is a
      yearly vaccine. The three-valent vaccine is in common use. It is recommended that
      high-risk population should be vaccinated. If the composition of the vaccine is
      well matched with the prevalent virus strain, it is efficient in 50-80% of
      vaccinees. CONCLUSION: Influenza is the sixth cause of death in the world, the
      forth among the older population. The next pandemic can occur at anytime. It will
      be a different virus subtype, never before encountered by humans. Are we ready?

PMID- 10965681
TI  - [Clinical significance and pathogenic mechanisms of insulin resistance in chronic
      renal insufficiency (part II): pathogenic factors of insulin resistance in
      chronic renal insufficiency].
AB  - INTRODUCTION: Factors implicated in the pathogenesis of insulin resistance in
      chronic renal failure are: uremic toxins, exercise tolerance, metabolic acidosis,
      secondary hyperparathyroidism, vitamin D deficiency. Many of them may contribute,
      but are not the main cause of insulin resistance in uremia. The aim of this
      review is to debate about each, separately. UREMIC TOXINS: Hippurate and
      pseudouridine are specific for uremia and inhibit glucose utilization at
      concentrations found in sera of uremic subjects. Partially purified toxins from
      uremic sera, after hemodialysis therapy, ameliorate beta-cell response to
      hyperglycemia and increase tissue sensitivity to insulin. EXERCISE INTOLERANCE:
      Exercise intolerance is common among hemodialysis patients, and also it can be
      the cause of insulin resistance. Moderate endurance training program improved
      both the exercise tolerance and insulin sensitivity in patients on hemodialysis.
      METABOLIC ACIDOSIS: Metabolic acidosis is frequent in uremia, but not in
      hemodialysis patients. Treatment of metabolic acidosis increases insulin
      sensitivity and insulin secretion, but significant degree of insulin resistance
      still exists in uremic patients. SECONDARY HYPERPARATHYROIDISM: After surgical
      correction of hyperparathyroidism, in hemodialysis patients, glucose tolerance
      and insulin secretion increase without significant changes in insulin
      sensitivity. Defect in insulin release attributable to reduced ATP content in the
      pancreatic islets induced partially by high intracellular calcium, secondary to
      augmented PTH-induced calcium entry into cells. VITAMIN D DEFICIENCY: Acute and
      chronic intravenous 1,25-Dihydroxycholecalciferol therapy corrects insulin
      resistance in dialysis patients, in absence of PTH suppression. These results are
      consistent with the hypothesis that 1,25(OH)2 D3 deficiency is a primary factor
      of insulin resistance. ERYTHROPOIETIN THERAPY: Corrects insulin resistance beside
      anaemia. CONCLUSION: Now we know more about pathogenesis of insulin resistance in
      uremic patients, and we must begin with early treatment of every pathogenic
      factor. Insulin sensitivity improved after hemodialysis, although it was still
      lower than control values.

PMID- 10965682
TI  - [Clinical significance of analysis of immunoglobulin A levels in saliva].
AB  - SALIVA COLLECTION: Whole saliva is a product of secretion of 3 major glands
      (parotid, submandibular, sublingual) and many minor glands (labial, buccal,
      palatal). Unstimulated saliva is usually obtained as the patient spits out every
      60 sec. or by forward bended head the patient allows saliva to drip off the lower
      lip into a cylinder. By collection of saliva in the tube the flow rate per unit
      time can be measured. When volume measurement is not required the saliva can be
      collected on cotton rolls, gauze or filter paper. For evaluating salivary gland
      function or when large volumes of saliva are required for analytic purposes,
      stimulated whole saliva is used. Method of collection is the same as for
      unstimulated saliva. The usual masticatory stimuli are paraffin wax or a washed
      rubber band. A standard gustatory stimulus is obtained by 2% citric acid applied
      directly to the tongue every 15 to 60 sec. Parotid saliva can be collected by
      aspiration from the duct opening with a micropipette. Parotid saliva is best
      collected with Lashley's vacuum chamber. Submandibular and sublingual saliva can
      be collected by cannulation of the duct with micropipette, but in practice this
      is both uncomfortable for the patients and technically difficult since the duct
      orifice is mobile and has a strong sphincter. Because of that, alginate and
      silicone impression material is used for retention of the collecting tube. As
      alternative and simple technique is to block off secretion from the parotid
      glands with absorbent swabs and collect mixed submandibular and sublingual saliva
      by pipette from the floor of the mouth. Saliva from labial and palatal glands can
      be collected by filter paper disc or disc of other synthetic materials. SALIVARY
      IMMUNOGLOBULIN A: The most significant characteristics of the salivary
      immunoglobulin system are quantitative domination of immunoglobulin A, local
      synthesis and specific structure. Immunofluorescence studies have shown that
      immunoglobulin A is produced by plasma cells locally in the salivary glands.
      There is still little convincing evidence for the origin of predominantly
      immunoglobulin A secreting plasma cells in salivary glands. DETECTION OF
      IMMUNOGLOBULIN A IN SALIVA: Radial immunodiffusion (RID) was the most applicable
      method for detecting salivary immunoglobulin A. However, there are more sensitive
      and automatic methods such as nephelometry and ELISA. A standard level of
      immunoglobulin in saliva is still in question since the concentration varies in
      relation to origin of saliva, method of collection and stimulation of secretion
      (Table 1). PERIODONTAL DISEASE: Studies of the salivary immunoglobulin A in
      patients with periodontal disease and healthy persons showed that there are
      differences which can be used in detection of high-risk groups and individuals.
      If the bacterial adherence to the mucosa is a prerequisite for bacterial
      evolution in subgingival or any other region of the oral cavity respectively
      introduction in periodontitis development, than it is to be presumed that the
      basic function of salivary immunoglobulin A is inhibition of bacterial adherence
      rather than antigens destruction. Several bacterial species frequently isolated
      from the oral cavity of patients with periodontitis have been identified as
      producers of IgA protease. These enzymes cleave serum IgA and secretory IgA
      equally well. Additionally, most of the IgA proteases studied have cleaved the A1
      and A2 subclass. Several studies have demonstrated that cleavage of human IgA
      occurs in vivo, resulting in generation of intact Fab alpha and (Fc alpha)2
      fragment. Moreover, when bacteria are exposed to Fab alpha fragments released
      from IgA after cleavage by IgA protease, their surface antigens are likely to be
      occupied by Fab alpha fragments. These Fab alpha fragments left on the bacterial
      surface may mediate adhesion. Together, these results indicate that IgA
      proteases, by promoting adherence, contribute the pathogenic potential of
      bacteria in the oral c

PMID- 10965684
TI  - Myocardial revascularization with skeletonized left mammary artery.
AB  - Graft selection has a direct influence on overall morbidity and mortality in
      patients selected for coronary artery bypass grafting (CABG) procedures. In the
      last decade internal mammary artery has been established as a conduit of choice
      for myocardial revascularization. However, there is still no official policy
      which operative technique has advantage in harvesting of the internal mammary
      artery (IMA). Current dilemma is whether pedicle or skeletonized grafts are
      better in immediate and long term results. Method of skeletonization of IMA
      increases surgeon's technical demands, but on the other hand has many advantages.
      Precise operative technique and selective preparation of IMA without concomitant
      elements reduces trauma to the chest wall, enables elongation and ideal graft
      positioning, and reduces graft compression by hyperinflated lungs. Complete graft
      visualization allows inspection of internal mammary artery in entire length,
      which excludes possibility to implant dissected or hypoplastic graft. From June
      1996 we started using the method of skeletonization of IMA, and until February
      1st 1999 skeletonized IMA was used as a conduit in 1001 patients. In our hands
      myocardial revascularization with IMA is a procedure with minimal morbidity and
      mortality. Precise operative technique during the harvesting of IMA is advantage
      especially in diabetics, old patients and patients with chronic obstructive
      pulmonary disease (COPD), that were considered as limiting factors for IMA use in
      the past. Our initial results with the quality of this conduit encourage us to
      extend the indication for using IMA as a dominant graft in multiple myocardial
      revascularization.

PMID- 10965683
TI  - [Implementation of a quality control system in transfusion practice].
AB  - Quality assurance and improving systems, standardization of all transfusion
      procedures as well as quality control and standardization of prepared blood
      products are necessary elements for work of transfusion centers in the future.
      Requirements for blood and/or blood products for therapy are: safety, adequate
      concentration of all active components needed, and treatment efficacy. To satisfy
      these requirements, we decided to adjust the work process of transfusion service
      to requirements of ISO 9001 standard series. To achieve this aim, quality control
      system documentation is created. Creation of quality control system documentation
      is one of the most difficult and most comprehensive parts the quality control
      system implementation process. The quality policy is adopted, whereas the basic
      procedures for blood products quality control, which are the subject of this
      paper, are created.

PMID- 10965685
TI  - [Effect of hyperlipoproteinemia on blood fibrinolytic activity and thrombocyte
      aggregation].
AB  - BACKGROUND AND AIM: An impaired lipid metabolism and macrovascular disease are
      often associated with diabetes mellitus. Effects of hyperlipoproteinemia on
      fibrinolytic blood activity and platelet aggregation were investigated in
      noninsulin-dependent diabetes mellitus. MATERIAL AND METHODS: The study sample
      consisted of 50 patients with noninsulin-dependent diabetes mellitus, only on
      dietetic regime. The following was studied: lipids (total cholesterol, HDL
      cholesterol and total triglycerides) fibrinolytic blood activity and platelet
      aggregation in patients with increased levels of cholesterol and triglycerides.
      We used enzymatic methods for lipids, Buckell's method for fibrinolysis (> 180
      min) and Crean's method for platelet aggregation (6-8 s). RESULTS: Statistical
      analysis of the obtained results shows significant changes in lipids.
      Triglycerides were significantly higher in diabetics with poor control (p <
      0.01). Total cholesterol was significantly higher in patients with coronary
      disease, hypertension and diabetics with occlusive disease of low extremities (p
      < 0.01). HDL cholesterol was significantly lower in diabetics with coronary heart
      disease (p < 0.05). Statistical analysis showed significant changes in blood
      coagulability. Decreased fibrinolytic blood activity (158.10 + 31.3 min v.s.
      169.82 + 21.05 min) (p < 0.05), as well as faster platelet aggregation (6.7 +
      0.48 sec v.s. 6.8 + 0.93 sec) (p < 0.1) in patients with hypertriglyceridemia
      compared with the diabetics with normal triglycerides. Other lipids did not
      influence significantly the fibrinolysis and platelet aggregation in noninsulin
      dependent diabetics. CONCLUSION: All of this indicates the importance of the
      studied factors in the onset of atherosclerosis with patients with noninsulin
      dependent diabetes; the latter is relevant to the importance of planned diabetic
      regime and moderate physical activity in preventing vascular complications of
      diabetes.

PMID- 10965686
TI  - [Depression in older persons].
AB  - INTRODUCTION: Depression is a common problem in old age, especially among those
      with various medical illnesses. Aging brings about numerous losses that might
      lead to depression: loss of health, loved ones and social roles. Some of older
      persons develop depression. Depression in old age is a serious illness. The
      suicide rate among older persons is very high. Approximately 90% of elderly
      people who commit suicide suffer from depression. Adequate treatment of
      depression in late life includes reducing and resolving depressive symptoms,
      preventing its relapse and reoccurrence, improving quality of life, and reducing
      mortality and healthcare costs. MATERIAL AND METHODS: 32 female inpatients were
      examined. All patients suffered from depressive disorder (middle, according to
      International Classification of Diseases (ICD-X). Only patients without cognitive
      impairment were included in the study, according to Mini-Mental State
      Examination. Hamilton Rating Scale for Depression was used as primary measure of
      efficacy. Patients were evaluated for efficacy weekly. For statistical analysis t
      test was used. RESULTS: Depressive disorders are more severe among older
      patients, with greater suicidal risk, anxiety and psychomotor agitation. Patients
      treated with moclobemide show quicker remission of depressive symptoms compared
      to patients who were treated with mianserin. CONCLUSION: Depressive disorders
      among older patient are very serious illnesses, but with adequate therapy,
      symptoms can disappear, and there is no difference between remission in
      depression among older and younger patients.

PMID- 10965687
TI  - [Arthroscopy of the knee--"surgery without complications"].
AB  - INTRODUCTION: Beside other advantages that arthroscopic surgery has, comparing to
      the open surgery, there is one more--the risk of complications is present but a
      very little. The aim of this work is to present complications that we have had
      and to point at possibilities how to prevent and treat them. MATERIAL, METHODS
      AND RESULTS: In the period from September 1990 to December 1998, 1071
      arthroscopic surgeries were performed in our hospital. 817 patients (76%) were
      male and 254 (24%) female, average age 30.63 (12-69). Left knee was involved in
      560, while the right in 511 cases. Among all arthroscopic interventions 463
      (43.23%) were diagnosed when damages of LCA or cartilage were seen, and 608
      (56.76%) were patients with therapeutic arthroscopic interventions. Among
      different arthroscopic interventions medial meniscectomy was performed in 417
      (38.93%) patients, lateral in 124 (11.57%), removal of joint loose bodies in 39
      (3.64%), reconstruction of LCA in 29 (2.70%), operation on patellar and condylar
      cartilage in 26 (2.42%) etc. There were 39 (3.64%) complications. 10 (25.64%) of
      them were intraoperative (breakage of arthroscopic instruments, loss of meniscal
      parts, extravasation of the fluid in extremity and 29 (74.35%) of them were
      postoperative (infection, synovial sinus, thrombophlebitis, haemarthrosis,
      synovial effusion, painful scar). 8 (1.72%) of those complications appeared after
      diagnostic arthroscopy and 31 (5.09%) after different therapeutic arthroscopic
      procedures. DISCUSSION: Advantages of arthroscopic surgery are exhibited in
      different ways (shortening hospital stay, lower cost of treatment, shortening the
      time necessary for complete recovery and return to everyday life and sport
      activities), while the risk of complications, although possible, is significantly
      diminished. Insufficient education, improvisation, rude manipulation, unprecise++
      surgical approaches to the knee joint lead to aforementioned complications. Our
      results are discussed and compared to those found in the literature giving
      suggestions in the same time how to avoid and prevent them. CONCLUSION:
      Orthopedic surgeons who perform arthroscopic surgery must be well trained and
      familiar with the arthroscopic procedures and able to prevent and overcome
      possible complications. Continual education and training is necessary for
      arthroscopic surgeons in order to be able to follow innovations in surgical
      techniques and instrumentation.

PMID- 10965688
TI  - [Drainage of the abdominal cavity and complications in perforating appendicitis
      in children].
AB  - INTRODUCTION: Controversies regarding drainage and irrigation with antibiotics
      following perforated appendicitis still exist in literature. Some authors
      concluded that undrained patients treated with systemic antimicrobial therapy,
      adequate fluid resuscitation, emergency appendicectomy, peritoneal lavage and
      primary abdominal wall closure are less exposed to complications. On the other
      hand, Lund and Murphy and Schwartz and Tapper are still advocating
      transperitoneal drainage. In that context the aim of this study was to contribute
      to the current debate with its original results and conclusions. MATERIAL AND
      METHODS: A series of 56 children, who were operated on for perforated
      appendicitis during 1996 in Children's Hospital Podgorica and Pediatric Surgery
      Department of Hospital in Novi Sad, are reviewed. The average age of children in
      this series was 9.8 years (range, 2-14 years). All children were divided in two
      groups: patients included in the first group (n = 36) were treated with
      aggressive fluid resuscitation, preoperative triple antibiotic therapy,
      peritoneal lavage, avoidance of transperitoneal drains except those used for well
      localized abscesses, primary wound closure and postoperative antibiotic therapy
      for seven to ten days. In the second group, children were managed in the same
      way, but silicon tube drainage after appendicectomy was included as well.
      Patients in both groups were given the same antibiotic therapy: intravenous
      metronidazole combined with gentamicin and ampicillin. RESULTS: Perforated
      appendicitis most frequently occurred in the age group between 8 and 15 years
      (77%), with highest incidence in male children (61%) of all children observed.
      Positive cultures were obtained from peritoneal swabs from 32 children (57%), of
      which all had pure growth of aerobes (Escherichia coli and Pseudomonas
      aerugionosa, mixed or pure). 36 children were managed by appendectomy followed by
      peritoneal lavage using a large amount of saline, and intravenous antibiotic
      therapy (undrained group), while the other 20 children were treated by
      appendectomy with silicon tube drainage and the same systemic antibiotic therapy
      (drained group). A minor complication rate was 43%; this includes 20 cases of
      wound infection and 4 cases of wound dehiscence. Major complications rate was 5%,
      which includes 3 cases of ileus. The mortality rate was zero. A comparison of the
      group that underwent drainage with undrained group showed a relative rate of
      wound infection to be 19% (undrained) vs. 65% (drained). According to the x2
      test, this can be considered a significant difference, with Yates' correction.
      Wound dehiscence and ileus were more frequent in the drained group: 10% vs. 6%
      and 19% vs. 3%, respectively. DISCUSSION: The principal factors contributing to
      perforation of appendix are: age of children, delays of surgical intervention,
      family anamnesis, social group and late recognition of symptoms of appendicitis.
      Fast and adequate surgical intervention followed by adequate antibiotic therapy
      successfully resolve the cases of perforated appendicitis. The rate of serious
      post-appendectomy complications of 5-10% established by this study, can be
      considered as acceptable based on standards presented in the relevant literature.
      Regarding the reduction of wound infections following perforated appendicitis in
      children, aggressive therapy consisting of aminoglycosides combined with
      metronidazole have proven to be very efficient. Complications developed more
      frequently in the group of drained patients. Our results are in accordance with
      that achieved by authors cited in introduction: undrained patients are less prone
      to complications in comparison to drained patients. CONCLUSION: We achieved our
      lowest rate of serious complications following surgery for pediatric perforated
      appendix with the use of broad-spectrum antibiotic therapy, primary wound closure
      and without drainage. Regarding our results, we could propose the same treatment
      protocol to all in

PMID- 10965690
TI  - [Ganglioneuroma of the thoracic cavity in a child: case report].
AB  - INTRODUCTION: Ganglioneuromas are benign tumours that originate from the
      sympathetic chain. These kinds of tumours are most frequently benign neurogen
      tumours in childhood. Most often they are localized in the paravertebral area of
      posterior mediastinum. The tumour usually shows slow growth and patients are in
      most cases asymptomatic. These tumours are well encapsulated and surgical
      excision results in cure. CASE REPORT: We report a case of a 9 year-old boy with
      subpleural ganglioneuroma. When the child was admitted in hospital he had a
      pathological auscultatory pulmonary finding. The tumour was revealed by
      radiological examination during respiratory infection. Preoperative differential
      diagnosis included a number of intrathoracic lesions in the area of posterior
      mediastinum. The patient was operated with success. CONCLUSION: It is not clear
      if coughing was the only symptom of respiratory infection or a sign of
      intrapulmonary compression of the tumours mass. Intraoperative findings confirmed
      that the tumour was extirpated on time. Pulmonary parenchyma was without damage.

PMID- 10965689
TI  - [Prenatal diagnosis of skeletal dysplasia: case report of a fetus with multiple
      anomalies].
AB  - INTRODUCTION: Skeletal anomalies are in the group of anomalies most difficult to
      be diagnosed antenatally. But, because of high lethality and morbidity rate as
      well as high possibility to be found again in the next pregnancy, they need to be
      systematically and actively looked for during every scan. CASE REPORT: A pregnant
      woman, aged 18, primigravida, was admitted to the Dept. of Obstetrics and
      Gynaecology because of polyhydramnios and suspected multiple fetal malformations.
      Fetal biparietal diameter and abdominal circumference were adequate for 33 weeks
      gestation, whereas all the long bones were short for the gestational age. A
      detailed ultrasound morphology check was impossible because of the excessive
      amount of amniotic fluid, but the skull, brain, lungs, spine and abdomen appeared
      normal. There was an impression of frontal bossing and left-sided cleft lip. A
      thoraco-abdominal disproportion was evident. All the extremities were short, feet
      were normal, and hands were not extended during the whole scan. The woman
      underwent an uneventful amino-drainage and three days after that she ruptured the
      membranes, giving birth to a live female, 2150 gr, 46 cm, Apgar score 6/7. The
      anomalies seen on ultrasound were confirmed after birth. After a series of
      dyspnea the neonate was transferred to the Dept. of Paediatrics where it
      underwent a series of further extensive diagnostic procedures and 37 days after
      birth it passed away. Postmortem examination led to the following diagnoses:
      Neonatus femininus eutrophicus temporis aetatis. Defectus partis memebranacei
      septi interventricularis. Ductus arteriosus Botalli persistence. Hypoplasia
      thymi. Cheliognathopalatoschisis. Low set ears. Extremitates breves. Atelectasis
      subtotalis pulmonis bilateralis. Foramen ovale apertum cum valvula competent.
      Oedema cerebri gradus maioris. DISCUSSION: Majority of fetal skeletal
      malformations can be relatively easily visualised during ultrasound scans and
      hence ultrasound is the most sensitive way of prenatal diagnosis of these
      anomalies. Maternal habitus, fetal position, alteration of amniotic fluid volume
      and gestational age can be factors that may aggravate check-ups. A prerogative
      for an early prenatal diagnosis of fetal skeletal anomalies is a well organized
      scan of each and every fetus that checks all bones, starting with the skull and
      finishing with hands and feet. Should an anomaly be found an extensive detailed
      scan by an expert should be performed, as well as karyotyping and a consultation
      with pediatrician/surgeon. In case of a lethal anomaly, an option of pregnancy
      termination should be considered and if the parents decide against it, the
      pregnancy should be closely monitored, with parents fully counseled about the
      prognosis for the child. In this case the anomaly was noted only after the 30th
      week of gestation and even then only because the patient came because she had
      some subjective difficulties because of the excessive amniotic fluid volume. On
      the other hand, some skeletal dysplasias can be diagnosed only in the late
      second, early third trimester and sometimes stay unnoticed until the end of
      pregnancy. This case could not be resolved definitely, for the anomalies were
      conclusive neither of a specific genetic syndrome, nor of an isolated skeletal
      dysplasia. Extensive further examination of parents as well as their families is
      needed in order to be able to give some information about the risks in the next
      pregnancy. CONCLUSION: Although skeletal anomalies are extremely difficult to
      diagnose antenatally, a detailed scan of a complete fetal anatomy between 20 and
      32 gestational weeks with special attention given to the entire skeleton, gives
      certain assurance of excluding majority of major skeletal dysplasias or enables
      their diagnosis and further adequate plan for pregnancy management.

PMID- 10965691
TI  - [Risk factors for development of cerebrovascular stroke].
AB  - INTRODUCTION: Nowadays stroke has a dominant place in the structure of
      neurological morbidity. According to data of the World Health Organization,
      stroke is the third highest cause of morbidity and mortality in the developed
      countries of the world, immediately following ischemic heart disease and
      malignant diseases. The appearance of the disease is influenced by many
      etiological factors, that is risk factors. Natural risk factors are: heredity,
      sex, age, geographical and climatic factors. Other diseases being risk factors
      include: hypertension, heart disease and diabetes. Bad habits as risk factors
      are: eating habits, obesity, smoking, alcoholism and physical and mental
      inactivity. The paper presents a review of risk factors, their categorization and
      the influence of each individual risk factor on the development of stroke.
      HEREDITY: Hereditary factors have a significant role in development of stroke and
      they may serve as a basis for determining the person's susceptibility to stroke
      in a certain period of life. SEX: It has been proved that persons of female sex
      in the period prior to menopause are less susceptible to atherosclerosis risk and
      its side effects--ischemic heart disease and stroke. It is due to the fact that
      in this period of life women have a higher concentration of high-density
      lipoproteins, which are known to protect blood vessels against atherosclerosis.
      AGE: The incidence of stroke is higher at an older age, although nowadays there
      is evidence that younger people may develop the disease as well. CLIMATIC
      FACTORS: It has been noticed that the frequency and intensity of insult are
      connected with abrupt changes of the front (weather conditions with certain
      values of atmospheric factors). A high correlation between the frequency of
      cerebrovascular insult and abrupt change of the front is evident during spells of
      warm front in cold months and during spells of cold front in warm months.
      Moreover, changes during the circadian cycle are of utmost importance.
      HYPERTENSION: Hypertension is one of the factors contributing to the development
      of cerebrovascular insult, apart from heart diseases and diabetes. HEART
      DISEASES: The most frequent heart diseases correlating with stroke are:
      endocardial diseases, myocardial diseases in the form of chronic heart failure or
      heart attack, atrial fibrillation, hypertrophy of the left chamber and congestive
      heart failure. DIABETES MELLITUS: Diabetes as an associated risk factor
      correlates with stroke. EATING HABITS: A special emphasis is placed on nutrition
      as a risk factor in development of stroke. Inadequate nutrition contributing to
      the development of stroke is primarily nutrition which includes a high percentage
      of fats and leads to hyperlipoproteinemias. Therefore the basic principle in the
      nutrition of a patient with hyperlipoproteinemias is to limit the overall intake
      of fats, to reduce the quantity of saturated fats and to increase the intake of
      unsaturated fatty acids. In order to prevent stroke it is recommended to consume
      sea fish, legumes rich in diet plant fibres, oats and corn cereals, whole grain
      rice, fruit and vegetables rich in vitamins C and E. OBESITY: It has been proved
      that obesity or increase in body weight increases the risk of developing stroke
      by 1.4 to 2.5 times. SMOKING: Smoking accelerates the process of atherosclerosis
      leading to the incidence of myocardial and brain stroke. In proportion to the
      length of smoking and the number of cigarettes, a relative risk of development of
      stroke goes from 2.4 to 6.1 for men and from 3 to 3.7 for women. ALCOHOL
      DRINKING: A research performed by Finnish authors has shown that in chronic
      alcoholism the risk of developing stroke is twice as high in men and five times
      as high in women in relation to the general population. Alcohol reduces the
      regional cerebral flow by its toxic effect on the cerebral metabolism and thus
      induces vasospasm and hemoconcentration. (ABSTRACT TRUNCATED)

PMID- 10965693
TI  - [Long and slow].

PMID- 10965692
TI  - [Homeopathy].

PMID- 10965694
TI  - [TOR inhibitors for immunosuppression].

PMID- 10965695
TI  - [Backache].

PMID- 10965696
TI  - [UV light and skin cancer].

PMID- 10965697
TI  - [Hepatitis A. Diagnosis and prevention].

PMID- 10965698
TI  - Capillary leak. Pathogenesis and treatment.

PMID- 10965699
TI  - New halogenated agents: should I change my practice?
AB  - Sevoflurane and Desflurane are relatively new halogenated agents which make
      induction and control of depth of anaesthesia easier, recovery rapid and of good
      quality and they have less side-effects and toxicity. In children sevoflurane
      could replace halothane because it provides smooth and rapid induction with less
      cardiovascular depression and arrhythmias. Desflurane is not used because of its
      pungent odour. In adults sevoflurane could be preferred to desflurane because it
      allows rapid induction and laryngeal mask insertion or tracheal intubation
      without myorelaxants, a similar time of recovery, no clinical evidence for renal
      and hepatic toxicity, no more costs for anaesthesia for a lower MAC.

PMID- 10965700
TI  - Why should I change my practice of anesthesia? Opioids.
AB  - The selection of opioid drugs for anesthesia is often based on empirical judgment
      such as the selection of opioids with rapid elimination half-life for short
      surgical procedures (e.g. alfentanil), while opioids with longer elimination half
      life (e.g. fentanyl, sufentanil) are used for longer procedures. A better insight
      in the pharmacokinetic and pharmacodynamic differences between opioids allows a
      more rational selection of the drug and its dosing scheme, and will contribute to
      rapid recovery after anesthesia. As opioids are adjuncts to other anesthetic
      drugs, drug interaction principles should be considered when titrating the opioid
      administration.

PMID- 10965701
TI  - Why should I change my practice of anaesthesia: neuromuscular blocking agents.
AB  - BACKGROUND: Recently, four neuromuscular blocking agents have been introduced
      into clinical practice. The drug companies claim that these new drugs offer
      several important advantages. But is this true? Do the new neuromuscular blocking
      agents add anything to our clinical practice, and will their introduction really
      benefit our patients? Or will it only benefit the economy of the companies?
      PURPOSE OF THE LECTURE: In this lecture I shall try to update you on these new
      drugs and give you my personal bias on when to use the different (new and old)
      neuromuscular blocking agents.

PMID- 10965702
TI  - Strategies in body fluid replacement.

PMID- 10965703
TI  - Perioperative optimisation of fluid management improves outcome.
AB  - Mortality from high-risk surgery is close to 10% (20% with emergency). Poor
      outcome is linked to tissue hypoperfusion. Optimising fluid therapy has a good
      pathophysiological basis related to microvascular flow to the tissues and the
      risk of multiple organ failure. Metaanalysis showed the higher the risk of
      surgery the greater the benefit of fluid and flow optimisation. A direct
      technique (blood pressure is indirect) to manage fluid therapy measuring tissues
      perfusions has not yet fulfilled criteria (easiness, accuracy, less
      invasiveness). At present pulmonary artery catheter with continuous output
      measurement is the choice. The aim of the study is to assess the impact of fluid
      management to increase blood flow in high-risk surgical patient.

PMID- 10965704
TI  - United Kingdom national confidential enquiry into perioperative deaths.
AB  - The enquiry (NCEPOD) was established to examine simultaneously the anaesthetic
      and surgical circumstances surrounding the death of a patient undergoing surgery,
      it reviewed clinical practice and identified remedial factors in the practice of
      anaesthesia and surgery in order to improve the quality of care. Data were
      reported on every death occurred within 30 days of a procedure performed by a
      surgeon or gynaecologist under general or local anaesthesia, excepting obstetric
      deaths, and were collected int he sample of questionnaires to surgeons and
      anaesthesists involved. In high risk patient the optimisation of cardiovascular
      system with fluids, inotropic agents, beta-blockers and invasive monitoring may
      improve mortality (a speculative calculation reported 1,700 out 19,000 lives
      saved in 1994/1995 in UK). The majority of deaths occurred in emergency
      operations, urgent operations delayed for no operating theatre free during the
      day, training personnel which performed emergency operations during the night
      and/or postoperative care provided by non specialized clinicians, hospital not
      equipped with high dependency units (HDU), surgery undertaken although the
      predictable infaust outcome, they were all problems outlooked by the
      investigation. In conclusion improvements are necessary in hospital facilities
      and working pattern of surgeons and anaesthesists.

PMID- 10965705
TI  - Time to reconsider the pre-oxygenation during induction of anaesthesia.
AB  - Atelectasis is a frequent finding in paralysed and mechanically ventilated
      patients. Atelectasis, causing shunt, impairs oxygenation and could contribute to
      postoperative pulmonary complications. Pre-oxygenation used during anaesthesia
      induction causes atelectasis. A lowering of oxygen fraction from 100% to 80% does
      not shorten the safety time of apnoea period, particularly useful for a difficult
      intubation, but it reduces drastically the atelectasis incidence.

PMID- 10965706
TI  - [Positive end expiratory pressure in anesthesia].
AB  - It is well established that general anesthesia, with or without paralysis, causes
      profound changes in respiratory function. From a clinical point of view, the more
      important consequence of this impairment is a decreased efficiency of gas
      exchange, with a decreased blood oxygenation. The main reason of this respiratory
      embarrassment is the intraoperative occurrence of atelectasis, mainly in the
      dependent lung regions. The amount of atelectasis, computed through Computerized
      Tomography, correlates with the amount of intrapulmonary shunt; thus, alveolar
      collapse and ventilation/perfusion mismatching are considered the most important
      factors for poor respiratory function. This deterioration seems also to play a
      crucial role in obese patients, who have poorer respiratory function and gas
      exchange than normal subjects already in physiological conditions. Different
      ventilatory approaches have been tried to resolve and eventually prevent the
      anesthesia-induced atelectasis. In normal subjects, the sole application of
      positive end-expiratory pressure (PEEP) seems to be an useless tool for improving
      gas exchange, probably because of changes in hemodynamics functions. The only
      effective application of PEEP seems to be in association to an alveolar
      recruitment manoeuvre. As the anesthesia-induced atelectasis are also present in
      the postoperative period, this ventilatory approach may also be used to prevent
      this condition. In obese patients PEEP seems to have a major effectiveness than
      in normal subjects, with an improvement of lung volumes, respiratory mechanics,
      gas exchange and an occurrence of recruitment. However, further studies are
      necessary to define optimal value of PEEP and tidal volume for different types of
      patients.

PMID- 10965707
TI  - Nitric oxide: modulation of the pulmonary circulation.
AB  - Nitric oxide (NO) is synthetized throughout the body by the enzyme NO synthase
      (NOS), cyclic GMP transduction pathway causes pulmonary vasodilatation anti
      platelets aggregation and inhibition of leukocyte adhesion. Inducible NOS is
      expressed in leukocytes in response to a variety of inflammatory stimuli and can
      be inhibited by corticosteroids. Inhaled NO is a selective pulmonary vasodilator.
      In USA inhaled NO was approved by FDA for hypoxemic respiratory failure in
      infants and children. In adults it may be useful in various clinical therapy:
      pulmonary hypertension, lung transplantation, ARDS but new clinical
      investigations are necessary.

PMID- 10965708
TI  - Lung recruitment during ARDS.

PMID- 10965709
TI  - [Gas conditioning in artificial respiration].
AB  - The authors review the main systems used in the clinical setting to condition
      inspiratory gases during mechanical ventilation. More in details, the functional
      principles of hot water humidifiers and heat and moisture exchangers are
      described.

PMID- 10965710
TI  - Limiting harm in the ICU.
AB  - This year, the US Institute of Medicine has estimated that medical errors kill up
      to 98,000 Americans each year,1 a problem surpassing automobile fatalities. For
      patients on the medical ward, drug therapy is the primary intervention they are
      receiving yet medication errors occur in as many as 4% of inpatients.2 Although
      greater monitoring intensity and much lower nurse-patient ratios in the ICU may
      reduce the incidence of medication errors, the shear number if interventions
      dramatically increases the risk of error.3 Furthermore, the study by the
      Institute of Medicine only addressed a small part of the problem. The taxonomy of
      errors includes both "accidents" (skill-based errors) and intentional "mistakes"
      (knowledge-based and rule-based errors).2 Thus, the Institute of Medicine would
      not consider the proscribing of human growth hormone for cachexia an error unless
      the proscribed dose was not administered or it was given to the wrong patient. In
      the ICU, the risks associated with both kinds of errors are considerable. In this
      review we will focus on the second kind of errors and examine harms associated
      with the care of patients with sepsis.

PMID- 10965711
TI  - Splanchnic perfusion in intensive care patients.
AB  - Splanchnic vasoregulation is poorly understood. The tissue perfusion in the
      splanchnic region may be compromised in critically ill patients both because of
      the underlying disease and therapeutic interventions. Inadequate perfusion,
      dysoxia, and ischemia-reperfusion may trigger and modify an inflammatory response
      which may itself cause deterioration of the splanchnic perfusion.

PMID- 10965712
TI  - Cytopathic hypoxia. A concept to explain organ dysfunction in sepsis.
AB  - The most common cause of death in patients with sepsis is the multiple organ
      dysfunction syndrome (MODS). One important factor underlying the pathogenesis of
      MODS may be sepsis-induced alterations in cellular energy metabolism due to
      acquired intrinsic derangements in cellular respiration, a phenomenon that might
      be called "cytopathic hypoxia". A number of different biochemical mechanisms have
      been postulated to account for cytopathic hypoxia in sepsis, including reversible
      inhibition of cytochrome oxidase by nitric oxide, irreversible inhibition of one
      or more mitochondrial respiratory complexes by peroxynitrite, and activation of
      the nuclear enzyme, poly-(ADP-ribosyl)-polymerase.

PMID- 10965713
TI  - Tissue PCO2 as universal marker of tissue hypoxia.
AB  - The author reviews the relationship between tissue PCO2 and tissue perfusion; the
      use of gastric tonometry and sublingual tonometry are described.

PMID- 10965714
TI  - The relevance of nutritional status on body homeostasis.

PMID- 10965715
TI  - Assessment of immunological status in the critically ill.
AB  - The systemic inflammatory response (SIRS) results from various types of injuries
      such as severe infection, trauma, ischemia-reperfusion and major surgery
      including cardiac surgery with cardio-pulmonary bypass. This response involves
      immune cell activation and a complex network of proinflammatory cytokines, which
      may induce multiple organ failure when uncontrolled. The monocyte plays a central
      role in the response to infection with the release of TNF, IL-1, and IL-12. In
      addition, monocytes present antigens to T lymphocytes. An optimal antigen
      presentation requires the expression of MHC class II HLA-DR on monocytes surface
      and of co-stimulatory molecules such as CD54 on monocytes and LFA-1 on
      lymphocytes. It has become increasingly apparent that the pro-inflammatory
      response is balanced by concomitant anti-inflammatory mechanisms that results in
      monocyte deactivation, characterized by a decrease in HLA-DR expression and the
      release of anti-inflammatory cytokines such as IL-10. This counterregulatory
      response, if prolonged or predominant, may predispose the patient to a higher
      risk of infection. Further studies need to be conducted to precise: 1) the
      intensity of depression of the surface molecule expression assessing monocyte
      function, such as HLA DR and CD54; 2) the level of IL-10 and IL-12 release in
      patients with severe sepsis; 3) the immunomodulating effects of frequently used
      treatments in these patients with severe sepsis and in surgical patients; 4) the
      time course of recovery; 5) if the monitoring of HLA-DR, CD54, IL-10 and IL-12
      will better predict the clinical outcome than clinical parameters.

PMID- 10965716
TI  - Immunocompetence in the critically ill: understanding the problem.
AB  - The author reviews the main pathophysiologic and clinical aspects of MODS, with
      particular attention to the evaluation immunocompetence of the patients.

PMID- 10965717
TI  - Rational base and clinical results of immunonutrition.
AB  - The use of enteral formulas supplemented with immunonutrients has been
      demonstrated to modulate gut function, inflammatory and immune response after
      trauma in both experimental and clinical settings. Most studies have focused on
      glutamine, arginine, w-3 fatty acids and nucleotides. Glutamine is an important
      source of nitrogen and calories and might be particularly useful in depleted
      patients or in patients affected by small bowel syndrome. Its use in the critical
      patient remains controversial. Data collected in two different recent
      metaanalysis consistently confirmed that enteral formulas enriched with,
      arginine, w-3 fatty acids and nucleotides reduced infectious complications and
      hospital stay after planned surgery, and decreased infectious complications,
      hospital stay and ventilator days in the critically ill. Mortality seems not to
      be affected by enteral administration of immunonutrients.

PMID- 10965718
TI  - Measurement of pressure-volume curves in patients on mechanical ventilation.
      Methods and significance.
AB  - In critically ill patients measurements of pressure volume curves has been
      suggested as a method for assessing the severity of lung injury and for
      monitoring the evolution of the lung disease; it can also guide the ventilatory
      adjustments to optimize the mechanical ventilation. The static pressure-volume
      curves are impaired in acute respiratory distress syndrome (ARDS). The evaluation
      of the lower and upper inflection point on the pressure-volumes curves at the
      bedside of patients with acute respiratory failure means to apply a "protective
      ventilatory strategy". The combined application of positive end expiratory
      pressure (PEEP) to the level of alveolar recruitment and low tidal volume (< 6
      ml/kg) ameliorates the lung function and decrease mortality in ARDS patients.
      Routine monitoring with continuous technique is easy and develops good
      therapeutic practice.

PMID- 10965719
TI  - [P-V curve morphology. Physiological and clinical implications].
AB  - The authors describe the main aspects concerning interpretation and clinical
      implications of P-V curve tracings in patients with ARF; both the homogeneous and
      the multicompartment models are described.

PMID- 10965720
TI  - The measurement of the pressure-volume curves with computerized methods.
AB  - The authors analyze the physiological basis, technical aspects and clinical
      usefulness of several methods for pressure-volume curves determinations in
      mechanically ventilatory, acute respiratory failure patients.

PMID- 10965721
TI  - Bispectral analysis technology and equipment.
AB  - The Bispectral Index or "BIS" is a single number, composed from different EEG
      features, using multivariate statistical methods. It was designed for monitoring
      the depth of hypnosis during anaesthesia and sedation. Empirically derived from
      the EEGs of more than 5,000 anaesthetised patients, the BIS reflects the effect
      of anaesthetics on the brain. Unlike univariate measures, such as Spectral Edge
      Frequency or Median Frequency, the Bispectral Index is drug independent and
      changes with increasing doses of hypnotics in an almost linear way. Though
      sophisticated technology, the A-2000 BIS monitor and the BIS sensor are easy to
      use and also allow non-experts to monitor the depth of hypnosis and sedation on a
      routine basis.

PMID- 10965722
TI  - [The utility of bispectral index monitoring in general anesthesia].
AB  - BACKGROUND: The Bispectral Index (BIS), a parameter derived from the
      electroencephalograph, has been shown to correlate with increasing sedation and
      loss of consciousness. This study was designed to investigate whether using BIS
      would improve anaesthetic drug management and immediate recovery after
      anaesthesia. METHODS: 160 patients undergoing abdominal surgery were studied. The
      patients were randomised to receive either propofol or sevoflurane anaesthesia.
      In each group 40 patients were anaesthetised with BIS monitoring and 40 without
      BIS. In BIS groups, propofol and sevoflurane dose was adjusted to achieve a
      target BIS values between 40-60 during the whole procedure. Drug consumption,
      intraoperative responses, times of recovery after anaesthesia and a "Clinical
      Quality Scale of Recovery" score were recorded from blinded observators. RESULTS:
      Demographic data were similar between groups. BIS monitoring improved the
      immediate recovery after propofol anaesthesia, while no significant differences
      were observed in patients receiving sevoflurane. The consumption of both propofol
      and sevoflurane significantly decreased (30 and 40%, respectively). There was no
      significant differences in the incidence of intraoperative responses between
      groups. The BIS groups had a higher percentage of patients with better ICU
      assessments. CONCLUSIONS: BIS monitoring decreased the consumption of both
      propofol and sevoflurane and facilitated the immediate recovery after propofol
      anaesthesia. Intraoperative course was not changed. These findings indicate that
      the use of BIS may be a valuable guide of the intraoperatively administration of
      propofol and sevoflurane.

PMID- 10965723
TI  - [Bispectral index: clinical effectiveness and role in reducing anesthetic drug
      consumption].
AB  - A numeric value derived from bispectral analysis of EEG, the bispectral index
      (BIS), has been recently introduced as a monitor of the hypnotic component of
      anaesthesia. Application of BIS monitoring in anaesthesia appears extremely
      interesting to drugs titration and drugs economy, and in the evaluation of time
      for discharge in a one day surgery regimen. In this prospective study ASA I-II
      patients for Day-Surgery were enrolled in three groups: subaracnoid anaesthesia
      (SA), general anaesthesia (GA) with BIS and GA without BIS monitoring. At present
      35 patients for DS operative hysteroscopy were enrolled. No significant
      differences were measured between the GA groups. A longer time of recovery was
      necessary in the SA group. A greater amount of anaesthetic in BIS group could be
      attributed to a better monitoring of sedation which prevents intraoperative
      awakening.

PMID- 10965724
TI  - Bispectral index and anaesthesia in the elderly.
AB  - BACKGROUND: Due to pharmacokinetic and pharmacodynamic reasons, the elderly are
      at particular risk of incurring unwanted side effects of drugs commonly used in
      anaesthesia. The bispectral index (BIS) is an EEG-derived value that measures the
      sedative component of the anaesthetic state. The BIS could be useful in guiding
      titration of anaesthetic drugs in the elderly. METHODS: A review of the published
      data was performed by the authors in order to assess the suitability of BIS
      technology application to the geriatric population. RESULTS: Age-related EEG
      differences exist in the normal population but they do not affect the BIS. The
      BIS correlates with depth of sedation independently of age. Senile dementia may
      be associated with significantly lower BIS values. CONCLUSIONS: The BIS is a
      useful guidance for titration of anaesthetic drugs in the elderly. The presence
      of senile dementia may be a confounding factor in the interpretation of the BIS
      values during anaesthesia.

PMID- 10965725
TI  - [Percutaneous tracheostomy: technological development].
AB  - PDT based on Seldinger's technique is gaining wide acceptance in ICU patients,
      but the procedure has undergone various modifications during the past thirty
      years. The ten most known procedures and the target of their innovating content
      are briefly examined. The incidence of complications desumed from the literature,
      wide in some cases and limited or absent in others, is also considered. In many
      cases, the technological modifications of original procedures had two fundamental
      objectives: to increase it's safety and to reduce the operator-depencence of the
      procedure. According to the review of the literature (and our experience too) the
      increasing interest for percutaneous tracheostomy is the justified conclusion of
      the technological development of some dilatative techniques. With an appropriate
      training and the continuous endoscopic guidance, it is possible today to perform
      PDT in critically ill patients of ICU with a very low total complication rate.
      Even if the comparison between different techniques is not rich enough on
      prospective randomized studies, the global low rate of hemorrhage complications,
      of wound infection and of poor cosmetic result are surely demonstrated and
      probably related to the small skin incision and the tight fitness between tissues
      and the tracheostomy tube.

PMID- 10965726
TI  - [The timing of tracheotomy. Advantages of early timing].
AB  - Tracheotomy is widely performed in Intensive Care Units, but no general agreement
      exists about its correct timing in ventilated patients. Many articles examine the
      complications of long-term endotracheal intubation and tracheotomy; few data,
      however, relate these damages and ventilated patients outcome to tracheotomy
      timing. No universally accepted guidelines exist, but last years clinical
      practice prefer early tracheotomy, particularly if performed by percutaneous
      approach. Many authors suggest prospective and randomized clinical trials in
      order to evaluate tracheotomy performance correct time. At this time decision
      making must consider risks and benefits related to patient clinical conditions:
      at this regard some reports seem to advantage early tracheotomy.

PMID- 10965727
TI  - Drug development in anaesthesia: the remifentanil.
AB  - Drug development in anaesthesia poses specific challenges. Describing the
      development of remifentanil highlights some of these. A new drug in anaesthesia
      must achieve its clinical goals in all patients and significant levels of
      toxicity are unacceptable. Rather than asking, "What new drugs does the
      anaesthetist need?" it may be more relevant to pose the question, "How can we
      design drugs to do things better?". Recent trends in anaesthesia have led to the
      development of short acting agents--one of these agents, remifentanil, has been
      designed to provide a mu-opioid receptor agonist with a rapid and predictable
      offset of action. The insertion of an alkyl ester group into this 4
      anilidopiperidine molecule has resulted in a compound which, whilst retaining the
      desired mu-opioid receptor pharmacology, is susceptible to metabolism by non
      specific esterases in the blood and tissues. The rapid onset and offset of action
      means that the anaesthetist can deliver high doses of opioid resulting in stable
      anaesthesia and the lack of accumulation ensures that even after prolonged
      infusion remifentanil does not compromise recovery. This ability to control the
      anaesthetic process has relevance in both short and long procedures and the
      unique characteristics of remifentanil may also in the future prove to have
      utility in the intensive care setting.

PMID- 10965728
TI  - [Remifentanil in anesthesia and intensive care].
AB  - Remifentanil (R) is a novel short-acting mu-receptor opioid. R is in the same
      structural family as fentanyl and the other phenylpiperidines, but it differs
      from fentanyl because of its pharmacokinetic profile and its metabolism: R
      undergoes extrahepatic metabolism by blood and tissue nonspecific esterases. For
      these reasons the time required for decreases of any percentage plasmatic
      concentrations of R after termination of the infusion is independent of infusion
      duration. The pharmacokinetic profile of R is organ-independent and the dosing
      regimen must be regulated in elderly patients by reducing the bolus and infusion
      doses, and in obese subjects by calculating the intravenous dosages as a function
      of age and lean body mass. The placental transfer of R doesn't affect the newborn
      as recently described in literature but further and wider clinical experiences
      are needed for assessing the use of R in obstetric anesthesia. R causes either a
      reduction in the MAC of volatile anesthetics or a decrease in propofol
      requirements but it cannot be used as a sole anesthetic agent. R can be utilized
      to facilitate tracheal intubation without using muscle relaxants, to manage
      analgesia and sedation also in association with midazolam and/or propofol,
      furthermore as analgesic agent for monitored anesthesia care, for the critical
      patient in ICU and for the postoperative analgesia if a proper analgesic strategy
      had not been planned.

PMID- 10965729
TI  - [Anesthesia-analgesia with remifentanil. Instrumental, laboratory and clinical
      evaluations].
AB  - The option of analgesic anaesthesia without hypnotic was investigated in 13
      patients, submitted to general, orthopedic or urologic surgery. Induction and
      maintenance of anaesthesia was performed with syringe-pump infusion of
      remifentanil 1-->2.2 mcg/kg/m and cisatrecurium, 0.2/air with FIO2 0.3; ecg
      monitoring, sieric level of ACTH were studied. "Slipping 8 channels patterns"
      were observed without spindless and K complexes; only in 2 patients N2O 50% can
      be used for increasing the depth of narcosys; ACTH levels increases only after
      remifentanil infusion stop.

PMID- 10965730
TI  - The chain of survival. A review in year 2000.
AB  - Worldwide about 1 in 1000 adults every year has a sudden cardiac arrest in out-of
      hospital. That means 350,000-400,000 persons in the USA alone, 60,000 persons in
      Italy. Over 70% of times sudden cardiac arrest occurs at home, the remaining 30%
      in public settings. The chain of survival concept emphasizes four links
      associated with survival after sudden cardiac arrest corresponding each with a
      set of actions that have been done as soon as possible--the early access, the
      early CPR, the early defibrillation, the early ACLS; in order to develop strength
      in each link, separate specialized programs are needed, but all of the links must
      be well connected. The Utstein Style was developed by a task force who suggested
      a series of recommendations as a starting point for more effective exchange of
      information about out-of hospital cardiac arrest. The Utstein Style includes a
      glossary of terms, a template for reporting data from resuscitation studies on
      cardiac arrest, definitions for time points and time intervals related to an
      intervention in a resuscitation attempt, definitions of clinical items and
      outcomes that should be included in reports, and recommendations for the
      descriptions for how different EMS systems are organized.

PMID- 10965731
TI  - Low-invasive haemodynamic monitoring.

PMID- 10965732
TI  - Adaptive changes in response to acute hypoxia, ischemia and reperfusion in human
      cardiac cell.
AB  - BACKGROUND: Previous studies have shown that biomolecular and biochemical
      adaptive changes antagonize oxidative damage due to hypoxia and ischemia in
      myocardial cells. The aim of our study was to verify in human ischemic and
      reperfused cardiac tissue the relationship between mitochondrial enzyme
      activities and the activation of HSP70 and c-fos synthesis in the context of a
      cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial
      respiratory chain enzyme activities in ischemic and reperfused tissue were
      investigated (preliminary report). METHODS: During elective coronary artery
      bypass grafting, in 30 consecutive patients ventricle samples were taken one
      before aortic clamping the second after 55 +/- 8 min ischemic period and the
      third 34 +/- 5 after final reperfusion. Coronary sinus blood samples were taken
      in parallel to assess free radical release measured by malondialdehyde (MDA)
      levels. In a small number of patients (N = 5) nitric oxide tissue levels were
      analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in
      cytochrome oxidase (COX) and succinate Cyt-c reductase (SCR) activities in
      ischemic and reperfused samples were observed. The activation of HSP70-72 and c
      fos transcription factor was evident in courses of ischemia and reperfusion.
      Blood MDA levels underline the concept that oxyradical generation characterizes
      peroxidative damage in reoxygenated myocardial tissue while adaptive changes
      which occur in ischemic cells seem to antagonize the oxyradical injury.
      CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent
      ischemic damage activating some peculiar biomolecular and biochemical adaptive
      changes which permit the reversibility of the oxidative injury. In contrast it
      appears evident that massive and rapid reoxygenation of the cardiac tissue leads
      to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a
      crucial role in cellular adaptation to ischemia even if further studies will be
      needed to elucidate these findings. From the data obtained in this work we cannot
      draw certain conclusions in terms of human cardiac cell adaptation to ischemia
      whereas it seems convincing that reoxygenation, as actually employed in clinical
      practice, compromises the integrity of the cells.

PMID- 10965733
TI  - Propofol 1% and propofol 2% are equally effective and well tolerated during
      anaesthesia of patients undergoing elective craniotomy for neurosurgical
      procedures.
AB  - BACKGROUND: The 2% formulation of the intravenous anaesthetic agent, propofol
      (Diprivan), delivers half the amount of lipid compared with the original 1%
      formulation. This may provide an acceptable alternative for patients who have an
      impaired ability to metabolise lipids. METHODS: This study was a multicentre,
      randomised, open comparison of parallel groups. Seventy-three adult patients
      undergoing elective craniotomy in neurosurgery were randomised to receive either
      propofol 1% (10 mg/ml) or propofol 2% (20 mg/ml) for induction and maintenance of
      anaesthesia. RESULTS: Analysis of induction time (199 s, 1%; 202 s, 2%; p > 0.05)
      and induction dose (1.13 mg/kg, 1.12 mg/kg; p > 0.05) shows that propofol 1% and
      propofol 2% are pharmacodynamically equivalent. Both formulations were similar
      regarding overall administration rates, recovery times, haemodynamic variables
      and tolerability. Plasma triglyceride levels, were lower in the propofol 2% group
      compared with the propofol 1% group, and significantly lower (p < 0.05) from 1 to
      4 hours after induction. CONCLUSIONS: We conclude that propofol 2% is as
      effective and as well-tolerated as propofol 1% for anaesthesia and is an
      acceptable alternative to propofol 1% in patients undergoing elective craniotomy
      in neurosurgery. The lower lipid load suggests it may be of particular benefit to
      patients with disorders of lipid metabolism.

PMID- 10965734
TI  - Measuring complexity/level of care and appropriateness of resource use in
      intensive care units.
AB  - BACKGROUND: Throughout the world, the cost of critical care medicine is
      increasing more than the overall health care cost. Thus, a higher attention to
      improve the efficiency of the use of ICU resources is indispensable. The
      objective of this study was the development of a simple and reliable tool for the
      evaluation of the appropriateness of ICU utilization. METHODS:  DESIGN: A
      repeated cross-sectional data collection was performed twice a week, during a 61
      day study period. SETTING: Twenty-three Italian general ICUs. PATIENTS: All
      patients present in the 23 ICUs on the 17 index days. INTERVENTIONS: On each
      index day, patients were checked for receiving ventilation/CPAP, pulmonary
      arterial pressure monitoring, intracranial pressure monitoring, vaso-active drug
      infusion and hemodialysis-ultrafiltration. Simultaneously, each ICU bed was
      assessed for its technical and personnel facilities in order to estimate the
      deliverable level of care. RESULTS: A total of 1250 patients were studied, for a
      total number of 7533 patient-days. The overall occupancy rate per ICU was 83.8% (
      range: 54.4% to 96.1%). The high-level occupancy rate (rate of patients requiring
      high level of care and actually occupying high-facility beds) was 69.4% (range:
      25.0% to 149.0%), while the corresponding low-level occupancy rate was 101.1%
      (range: 31.3% to 329.4%). CONCLUSIONS: Our model clearly showed up a certain
      degree of inappropriateness in the use of ICU resources. Most of the ICUs (69.6%)
      used a very large proportion of their high-facility beds for patients who did not
      need high-level care. Being very simple, our method could represent a useful tool
      for continuous evaluation of the appropriateness of resource utilization in the
      ICU.

PMID- 10965736
TI  - [Retinoic acid syndrome. Severe respiratory insufficiency treated with CPAP].
AB  - Retinoic acid syndrome is a potentially life-threatening complication of therapy
      for acute promyelocytic leukemia (APL) with all-transretinoic acid (ATRA). The
      case of a 55-year old male patient admitted to the hospital because of a bleeding
      diathesis is reported. APL was diagnosed and he underwent treatment with
      idarubicin and ATRA (GIMEMA protocol); 24 hrs after ATRA treatment he developed
      retinoic acid syndrome and was admitted to the Intensive Care Unit because of
      severe respiratory insufficiency (dyspnoea, tachypnea and severe hypoxemia (SpO2
      75%). Pulmonary insufficiency was treated non-invasively with CPAP and the
      patient recovered from pulmonary distress one week later.

PMID- 10965735
TI  - A prospective, randomized comparison of dexketoprofen, ketoprofen or paracetamol
      for postoperative analgesia after outpatient knee arthroscopy.
AB  - BACKGROUND: This prospective, randomized study was conducted to evaluate the
      quality of postoperative pain relief when using dexketoprofen, ketoprofen, or
      paracetamol after outpatient knee arthroscopy. METHODS: Without premedication, 45
      ASA physical status I-II patients undergoing elective outpatient knee arthroscopy
      with combined sciatic-femoral nerve block, were randomly allocated to receive
      either 25 mg oral dexketoprofen (n = 15), 50 mg oral ketoprofen (n = 15), or 500
      mg oral paracetamol (n = 15) before block placement. After completion of surgery
      the same pain medication was given according to standard protocols, while 50 mg
      oral tramadol were allowed as rescue analgesic if required by the patient. After
      standard discharge criteria had been fulfilled, patients were discharged from the
      day-surgery unit, while a telephone follow-up was performed the day after surgery
      using standard questionnaires evaluating the quality of pain relief during the
      first 24 hours after surgery. Total consumption of rescue tramadol, maximum pain
      complained of after hospital discharge, as well as the visual analogue scale of
      pain measured at hospital discharge were assessed by an independent trained
      observer. RESULTS: No differences in anthropometric variables, duration of
      surgical procedure, and fulfillment of discharge criteria were observed between
      the three groups. The degree of pain measured at rest at hospital discharge was
      similar in the three groups, while the VAS measured during motion was higher in
      patients receiving paracetamol (24 +/- 2.5 mm) than in those patients treated
      with dexketoprofen (13 +/- 6 mm) or ketoprofen (17 +/- 5 mm) (p = 0.016). Two
      patients (one in ketoprofen group and one in paracetamol group) required rescue
      tramadol after hospital discharge; however, no differences in maximum pain
      complained of after surgery or patient acceptance were observed between groups.
      CONCLUSIONS: This prospective, randomized study demonstrated that in outpatients
      receiving arthroscopic knee surgery, the use of 75 mg/day dexketoprofen was as
      effective and safe as 150 mg/day racemate ketoprofen, with a better pain relief
      during motion compared to 2 g/day paracetamol when patients were discharged from
      the day-surgery unit.

PMID- 10965738
TI  - [The "declaration of information and consent to anesthesia"].

PMID- 10965737
TI  - Non invasive ventilation in the treatment of FUdr-induced lesional pulmonary
      oedema.
AB  - 2-deoxy-5-fluorouridine, also known as floxuridine (FUdr) is a fluoropyridine
      antimetabolite, used in the treatment of metastatic renal cell carcinoma. We
      report the first case of lesional pulmonary oedema developed after receiving
      Fudr, recently treated in our unit. The patient refused endotracheal intubation,
      and was successfully treated associating noninvasive ventilation (NIV) with full
      face mask to steroid treatment. The authors conclude that mechanical ventilation
      via face-mask can be an effective, comfortable, dignified method of support for
      patients with end-stage disease and acute respiratory failure.

PMID- 10965739
TI  - [Care at the patient's bedside. Non-invasive bioethics].
AB  - This paper aims at describing the circumstances of the birth of Bioethics. In the
      first section, the paper points out some historical data supporting the widely
      diffused opinion according to which Bioethics started in the USA at the beginning
      of the '70s. In the second section, one of the most important factors in the
      birth of Bioethics is discussed: namely, the changes in medical enterprise and
      health care ethics. In the third section the impact of Bioethics on clinical
      medicine at the bedside is discusses, and, in the last section, one of the most
      important practical application of bioethical reflection is presented: the
      creation of Hospital Ethics Committees.

PMID- 10965740
TI  - [The responsibility of the medical professional in the evolution of
      jurisprudence].

PMID- 10965741
TI  - [A clinical study of secondary osteoporosis induced by endocrine therapy for
      prostate cancer].
AB  - PURPOSE: There is one of the big problems that endocrine therapy for prostate
      cancer causes to induce secondary osteoporosis. The risk factors and future
      treatments for osteoporosis were investigated. MATERIALS AND METHODS: 31 patients
      treated with luteinizing hormone releasing hormone agonists (LHRH-a) or
      combination of chlormadinone acetate (CMA) and LHRH-a, and 19 patients with no
      treatments for prostate cancer were included in the analysis. Lumber spine bone
      mineral density (BMD) was measured by quantitative computed tomography. RESULTS:
      Aging had much influence on decreases of BMD than the other risk factors (p <
      0.01). There were statistically decreases of BMD in the patients with CMA + LHRH
      a compared with no treatments (p < 0.05). Adrenal androgen which had an important
      role of maintenance in BMD was statistically decreased by the administration of
      CMA (p < 0.01). CONCLUSIONS: Measurement of BMD before endocrine therapy is
      necessary for the patients with prostate cancer. It is important for the patients
      with decreases of BMD that CMA is not combined or the therapy for osteoporosis is
      preventively employed.

PMID- 10965742
TI  - [Clinical evaluation of basic fetoprotein in bladder cancer].
AB  - PURPOSE: The early diagnosis of bladder cancer allows for effective local
      treatment and optimizes the success of surgical therapy. Basic fetoprotein (BFP),
      measured using a rapid latex immuno-agglutination method, was introduced for the
      detection of transitional cell carcinoma. The objective of this study was to
      determine whether there was a correlation between urine BFP level and the grade
      or stage of bladder cancer, and whether the level could serve as a biochemical
      marker of bladder cancer. MATERIALS AND METHODS: Single voided specimens were
      obtained from 66 patients with confirmed or suspicious bladder cancer on
      cystoscopy, urine cytology or BFP. Each sample was divided into 3 aliquots of
      which 1 was for urine analysis, 1 was tested for BFP according to latex
      immunoagglutination method and 1 was sent for cytological examination. All
      patients subsequently underwent bladder biopsy. RESULTS: There were 54 (82%)
      patients with biopsy confirmed bladder cancer and 12 (18%) with benign conditions
      of the bladder. Overall sensitivity with BFP and urine cytology was 38.9% and
      48.1% respectively. Specificity was 58.3% and 75.0%, and positive predictive
      value was 80.8% and 89.7%, respectively. The positive rate of BFP and cytology
      was higher in invasive cancer (75% and 100%, respectively) than in superficial
      cancer (36% and 28%). There was no correlation between BFP level and tumor grade,
      while cytology had a strong association. Linear regression analysis showed the
      significant correlation between BFP level and tumor size (r = 0.695, p < 0.0001).
      The detection rate of bladder cancer was higher by the combination of BFP and
      cytology than by using alone. CONCLUSIONS: BFP in conjunction with urine cytology
      can increase the detection rate of bladder cancer. But BFP alone cannot be used
      as a screening test for bladder cancer.

PMID- 10965743
TI  - [PSA doubling time in prostate cancer relapsed after endocrine therapy].
AB  - PURPOSE: The PSA level of prostate cancer patients generally declines after
      endocrine therapy, but elevates when the cancer relapses in most cases. However,
      the rate of elevation differs with the case. We investigated the PSA doubling
      time (PSA-DT) of the prostate cancer patients whose PSA declined after endocrine
      therapy and later re-elevated, and investigated the relationship with other
      parameters. PATIENTS AND METHODS: We investigated 55 prostate cancer patients who
      underwent endocrine therapy between 1991 and 1998. Their PSA re-elevated
      continuously after their PSA fell below 10 ng/ml after the endocrine therapy as
      the first line treatment. First, the correlation coefficients with time and PSA
      were calculated in order to decide whether their PSA elevation was exponential or
      linear. PSA-DT was calculated thereafter, and compared with the clinical stage,
      pathological differentiation, clinical relapse style, time from the beginning of
      the therapy to PSA relapse, pre-treatment PSA value, and prognosis. The
      relationship between PSA-DT and each clinical parameter was tested using the
      Kruskal-Wallis test. Differences in survival rates and PSA-DT were calculated
      using the log-rank test. RESULTS: PSA elevated exponentially after cancer
      relapsed. PSA-DT in all cases ranged from 0.5 to 26.3 months, with an average of
      4.4 +/- 4.8 (S.D.) months and the median was 2.5 months. PSA-DT was significantly
      (p < 0.01) short when the pre-treatment clinical stage was high, the time from
      the beginning of the therapy to PSA relapse was short, or the pre-treatment PSA
      value was high. PSA-DT tended to be short when the pre-treatment pathological
      differentiation was low, but not significantly. PSA-DT tended to be short when
      the cancer relapsed as distant metastasis rather than regional relapse, but not
      significantly. Prognosis from the initial treatment and PSA relapse was
      significantly poor when the PSA-DT was short. CONCLUSIONS: PSA elevated
      exponentially in the relapsed prostate cancer patients after the endocrine
      therapy. PSA-DT was distributed in a very wide range, and this value was
      considered to reflect the malignant potential and prognosis of the cancer. PSA-DT
      may be useful for determining the strategy after relapse.

PMID- 10965744
TI  - [Predictive factor for TESE (testicular sperm extraction)--ICSI (intracytoplasmic
      sperm injection) for non-obstructive azoospermia].
AB  - BACKGROUND: TESE-ICSI has been used very successfully in the treatment of the
      patients with non-obstructive azoospermia but its indication is still
      controversial. We performed retrospective study concerning parameters to predict
      successful recovery of testicular sperm from the patients and outcomes of ICSI.
      PATIENTS AND METHODS: 44 patients with non-obstructive azoospermia who underwent
      TESE-ICSI from July, 1997 to September 1999 were studied retrospectively.
      RESULTS: 1) Testicular sperm were retrieved from 32 patients (72.7%). ICSI was
      performed in 29 patients and the partner of 15 patients (46.9%) got pregnant.
      From 10 patients with histology of Sertoli-cell-only, we could retrieve sperm in
      3 patients (30%). 2) Testicular volume, Johnsen's score count (JSC), and FSH were
      significant parameter to predict the recovery of testicular sperm from the
      patients, but if we see only the patients with JSC less than 7, there were no
      significant parameter. Chromosomal abnormality was not a significant parameter.
      3) The partner's age, motility of recovered sperm and testicular volume
      correlated with fertilization rate. Chromosomal abnormality was not significant
      parameter to predict fertilization. CONCLUSIONS: There was no absolute parameter
      to predict the recovery of testicular sperm from the patients with non
      obstructive azoospermia. All patients with non-obstructive azoospermia can be the
      indication of TESE-ICSI.

PMID- 10965745
TI  - [A case of embolization to a large polycystic kidney with infection].
AB  - 75 year old female who was hospitalized for abdominal pain and fever up on 12th
      May 1998. She had been followed as a polycystic kidney patient since few years.
      The swelling of the right kidney and her general condition became gradually
      worse. On 18th May, the embolization to the right kidney using pure alcohol and
      gelatin sponge was performed. Within a month, CT scan showed the reduced volume
      of the right kidney and her blood examination data as well as her general
      condition became gradually well. And on 17th June, she left our hospital without
      any complication.

PMID- 10965746
TI  - [Chemotherapy in hemodialysis patient with metastatic testicular cancer;
      pharmacokinetics of etoposide and cisplatin].
AB  - The pharmacokinetics of intravenously administrated cisplatin and etoposide were
      studied in a patient with seminoma (stage IIIA) receiving hemodialysis for
      chronic renal failure. The treatment schedule was as follows: 7 mg/m2 of
      cisplatin at day 1, 3, 5; 14 mg/m2 of cisplatin at day 2, 4; 70 mg/m2 of
      etoposide at day 1-5; hemodialysis at day 2, 4. After the treatment
      myelosuppression was very strong. So the patient were received another treatment
      of smaller doses of cisplatin and etoposide in three courses. The other schedule
      was as follows: 14 mg/m2 of cisplatin at day 1, 3, 5; 35 mg/m2 of etoposide at
      day 1-5; hemodialysis at day 1, 3, 5. The area under the blood concentration-time
      curve (AUC) of free-cisplatin was 6.82 micrograms.hr/ml in first course, 4.07
      micrograms.hr/ml in second course. The peak concentration of peripheral blood
      free-cisplatin was 0.58 microgram/ml in first course, 0.43 microgram/ml in second
      course. The AUC of etoposide was 241.9 micrograms.hr/ml in first course, 216.9
      micrograms.hr/ml in second course. After treatment CR was observed and there was
      no recurrence for five years. In conclusion, it was considered that cisplatin and
      etoposide could be given to the patient receiving hemodialysis for chronic renal
      failure and smaller doses should be given to prevent side effects.

PMID- 10965747
TI  - [Differential diagnosis of focal areas of ground-glass attenuation in the
      peripheral lung 20 mm or less in diameter: high-resolution CT-pathologic
      correlation].
AB  - BACKGROUND: The detection and differential diagnosis of focal areas of ground
      glass attenuation (FGGA) is becoming important for early diagnosis of lung
      cancer. PURPOSE: The purpose of this study is to clarify the correlation between
      FGGA (20 mm or less in diameter) on high-resolution CT (HRCT) and histopathology
      of surgically resected lesions. MATERIALS AND METHODS: Ninety surgically resected
      peripheral lung lesions 20 mm or less in diameter with a greater than 50% area of
      GGA on HRCT from 58 patients (34 men and 24 women; mean age, 60.5 years) were
      studied. Sixty-nine lesions were adenocarcinomas (type A; 31, type B; 5, type C;
      32, type D; 1, according to Noguchi et al.), 11 were atypical adenomatous
      hyperplasias, and 10 were inflammatory lesions. HRCT findings were
      retrospectively evaluated with regard to maximum diameter, marginal character,
      internal dense attenuation domain, and linear density radiating into surrounding
      lung parenchyma. Statistical analysis was performed with Mann-Whitney's t-test,
      Pearson's correlation coefficient, and chi 2-test between each group of lesions.
      RESULTS: The maximum diameters on HRCT were significantly larger in
      adenocarcinomas (mean, 12.7 +/- 5.5 mm) than in atypical adenomatous hyperplasias
      (4.6 +/- 1.9 mm, p < 0.01) and in inflammatory lesions (5.9 +/- 2.7 mm, p <
      0.01). Among adenocarcinomas, the diameters of type C tumors (mean, 15.7 +/- 5.0
      mm) were larger than those of type A tumors (9.0 +/- 3.1 mm, p < 0.01). Linear
      density radiating into surrounding lung parenchyma was not found in inflammatory
      lesions, atypical adenomatous hyperplasias or type A tumors. Dense attenuation
      domains were found more frequently in type C tumors (94%) than in type A or type
      B tumors. Linear density and dense attenuation domain were both correlated with
      size of lesion (p < 0.05, p < 0.01, respectively). CONCLUSIONS: HRCT is useful in
      the diagnosis of early pulmonary adenocarcinomas presenting as small FGGA.

PMID- 10965748
TI  - [Malignant solitary fibrous tumor of the pleura: two cases and review of the
      literature].
AB  - We present two cases of malignant solitary fibrous tumor of the pleura (MSFT-P)
      and review 29 reported cases of MSFT-P. In examining the clinical and
      morphological features and prognosis of MSFT-P, we found that over 90% of the
      patients had some symptoms and one-third showed local recurrence. Chest
      radiographs and CT demonstrated large broad-based masses with necrosis,
      hemorrhage, and pleural effusion. The maximum diameter of the tumors was greater
      than 10 cm. Pleural effusion was seen in more than 70% of the patients, but there
      was only one case of pleural dissemination. All of the cases were well
      demarcated, and this was the most reliable finding for differentiating MSFT-P and
      malignant mesothelioma.

PMID- 10965749
TI  - [Experimental study of esophageal covered stent for prevention of migration: use
      of clay to simulate stenosis of the esophagogastric junction or anastomosis
      site].
AB  - PURPOSE: An inner-covered Spiral Z-stent (IC-SZ) developed by our group was
      examined for its effectiveness in preventing migration by experimental comparison
      with commercially available esophageal covered stents. MATERIALS AND METHODS: The
      following six types of stents were used: inner-covered Spiral Z-stents with
      diameters of 16 mm (small IC-SZ) and 19 mm (large IC-SZ), outer-covered Spiral Z
      stent (OC-SZ), covered Wallstent, covered Ultraflex stent, and Cook Z-stent.
      Experimental models were prepared using clay to simulate stenosis of the
      esophagogastric junction or anastomosis site due to tumor, and each stent was
      placed in the clay. After the stent had been fully expanded with a balloon
      catheter, one of its ends was pulled until the stent migrated out of the clay,
      and the traction force was measured. The inner cavity of the stent placed in the
      clay was observed using an endoscope. RESULTS: The mean maximal traction force
      required to pull the stents out of the clay were as follows, in decreasing order:
      4.14 +/- 0.39 kg for the large IC-SZ, 4.12 +/- 0.83 kg for the small IC-SZ, 3.64
      +/- 0.44 kg for the Cook Z-stent (p < 0.05), 3.34 +/- 0.62 kg for the covered
      Ultraflex stent (p < 0.05), 1.53 +/- 0.43 kg for the OC-SZ (p < 0.01), and 0.56
      +/- 0.16 kg for the covered Wallstent (p < 0.01). The force required to pull out
      the large IC-SZ stent was the greatest, showing a significant difference from the
      values for the other four types of stents (excluding the small IC-SZ).
      Observation using an endoscope revealed that the wire of the IC-SZ stent was
      almost entirely embedded in the clay, whereas the wires of other stents were not.
      CONCLUSION: The IC-SZ stent may be less likely to migrate than other esophageal
      covered stents.

PMID- 10965750
TI  - [Assessment of functional severity on in vivo hepatic 31P-MRS in diffuse hepatic
      disease: comparative studies with 99mTc-GSA].
AB  - The purpose of this study was to compare the assessment of functional severity on
      in-vivo hepatic 31P-MRS in diffuse hepatic disease with functional severity
      assessed with 99mTc galactosyl serum albumin (99mTc-GSA). 31P-MRS was performed
      in 10 healthy control subjects and 16 patients with diffuse hepatic disease. Data
      were expressed as peak area ratios: PME/beta-ATP, PDE/beta-ATP, PME/PDE, Pi/beta
      ATP, and PME/Pi. The functional severity of hepatic damage was evaluated visually
      and quantitatively (HH15, LHL15) by 99mTc-GSA in the group of patients with
      diffuse hepatic disease. Visual evaluation was classified into four grades based
      on anterior images of cardiac blood-pool and liver. We studied the correlation of
      spectral metabolic ratios and functional severity by 99mTc-GSA. We found
      statistically significant differences (ANOVA) among the classifications of Grade
      I, Grade II, and Grade III with both PME/beta-ATP and PME/PDE. A statistically
      significant direct correlation was found between HH15 and both PME/beta-ATP and
      PME/PDE. A significant inverse correlation was also seen between LHL15 and both
      PME/beta-ATP and PME/PDE. The studies comparing 31P-MRS with functional severity
      assessed by 99mTc-GSA showed that PME/beta-ATP and PME/PDE were useful for the
      assessment of functional severity in patients with diffuse hepatic disease.

PMID- 10965751
TI  - [Retrogastric colon mimicking foramen of Winslow hernia or left paraduodenal
      hernia: case report].
AB  - We report the case of a 54-year-old woman who developed epigastralgia and vomit.
      Because of the abnormal gas in the epigastrium on abdominal X-ray, ileus due to
      foramen of Winslow hernia or left paraduodenal hernia was suspected. However,
      abdominal CT and barium study revealed the gas in the epigastrium to be the air
      in the transverse colon interposed between the stomach and pancreatic body. This
      anomalous interposition of the transverse colon is called retrogastric colon. The
      ileus was due to non-specific inflammatory duodenal stenosis. It is important to
      prevent misdiagnosis of retrogastric colon as lesser sac pathologic condition
      such as abscess, bowel perforation and internal hernia.

PMID- 10965752
TI  - [Factors related to smoking behavior of nursing students revealed by a cohort
      study].
AB  - PURPOSE: Through a cohort study, changes in smoking behavior of nursing students
      and the factors related to their smoking behavior were examined. METHOD: Research
      through anonymous questionnaires concerning smoking behavior was conducted on
      nursing students in the first to third grades (as of 1997) at two vocational
      schools of nursing located in the Tokyo Metropolitan area. The same research was
      conducted in the same manner on the same subjects the following year. RESULTS:
      The smoking prevalence among nursing students of the first and second grades as
      of 1997 had increased by 10% in one year, and that of nursing students of the
      third grade (to graduate in 1998) had increased by 5%. The average degree of
      nicotine dependence of the subjects, who replied that they smoked every day in
      both surveys, increased from 4.25 to 5.00. As to factors related to smoking
      behavior, the smoking behavior of friends largely influenced that of the nursing
      students. CONCLUSIONS: Education to prevent nursing students from smoking should
      be started as soon as possible at vocational schools of nursing, because the
      research showed that more than 70% of the smokers had actually thought of
      quitting and that their views toward smoking influenced later smoking behavior.

PMID- 10965753
TI  - [Evaluation of hearing disorders and social support among the middle aged and
      elderly in the community. I. Analysis on the relationship between hearing
      difficulties and social participation, and self-rated health].
AB  - OBJECTIVES: To clarify the actual conditions of middle-aged and elderly community
      residents with hearing disabilities; and to investigate, through self-evaluation,
      the impact of hearing difficulties on health and social participation so that a
      key can be found to provide social support for residents with some degree of
      hearing impairment. METHODS: A questionnaire survey was conducted in Soyo village
      in Kumamoto Prefecture. The subjects of the survey were 2,199 residents aged 40
      years and older receiving health check-ups in accordance with the Health Service
      Act for the Aged. The questionnaires consisted of 8 items regarding self
      evaluations of health, hearing difficulties, the utilization of hearing aids,
      tinnitus, and social life. RESULTS: Data from 2,075 respondents who completed the
      questionnaire were analyzed. The results were as follows: 1. The number of
      residents claiming hearing difficulties according to age: 40 s--1 man (0.6%) 50 s
      -7 men (3.9%) and 7 women (2.8%) 60 s--26 men (8.3%) and 16 women (4.2%) 70 s(+)-
      42 men (17.5%) and 37 women (11.1%) The percentage of respondents suffering from
      hearing difficulties increased significantly with age with percentages higher in
      men than in women among all age groups. 2. Thirty-eight men and 32 women reported
      customary use of a hearing aid. Hearing aid use was 0.6% among men in their 40 s,
      1.1% in men and 1.2% for women in their 50 s, 3.2% in men and 1.6% for women in
      their 60 s, 10.4% in men and 6.9% in women in their 70 s or older. 3. Logistic
      regression analysis showed a significant association between hearing difficulties
      and social participation (Odds ratio: 1.56; 95% Confidence Interval, 1.02-2.38).
      The degree of social participation (participation in a variety of
      activities/communication by telephone) was restricted by hearing difficulties. 4.
      Logistic regression analysis showed a significant association between hearing
      difficulties and self-evaluated health (Odds ratio: 2.47; 95% Confidence
      Interval, 1.38-4.42. The elderly with hering difficulties tended to show lower
      self-evaluated health. CONCLUSIONS: This study suggests the necessity of creating
      and implementing social policies that deepen residents' awareness of hearing
      disabilities as invisible barriers in the home, in the workplace, and in the
      community; and the necessity of improving the living environment through the
      utilization of barrier-free designs that will foster better communication.

PMID- 10965754
TI  - [The effects of family interventions for the patients with mental illness in
      health centers focusing on the relatives' own life].
AB  - Recently, the burden on relatives of patients with mental illness has been
      recognized and the need for support to reduce such burden has increased. In
      Japan, family interventions have been conducted at Health Centers, most of them
      focusing on the family functioning as a caregiver. However, it is also important
      to focus on the relative's functioning to live their own life in family
      interventions. In this study, we executed a program focusing on relatives' life
      and health, and investigated the effects of this program on both family
      functioning. Family intervention programs were conducted at 10 Health Centers
      including both urban and rural areas in Japan. A total of 102 relatives responded
      to the self-administered questionnaire at the first and the last session of the
      family interventions. We measured functioning as a caregiver using the Support
      for the Disabled Score and Rejective Feeling Score, and functioning to live their
      own life by GHQ Distress in Daily life Score, Perceived Health Condition Score
      and Life Satisfaction Score. During interventions, GHQ score and Distress in
      Daily Life score which indicate the disfunction in living their own life
      decreased, and Support score increased in all sample. In the short-term illness
      group (n = 35), only the GHQ score decreased, while in long-term illness group (n
      = 44) Distress score decreased and Support Score increased. The intervention
      program focusing on relatives' life and health may improve both family
      functionings to give adequate care for patients, and to live their own daily
      life. Results suggested that the short-term illness group requires more intensive
      and personal advices, and the long-term illness group need continuous support
      focusing on the relative's own life. Expected roles of Health Centers are
      cooperation with family interventions provided at hospitals and coordination of
      the services in the community, as well as providing family interventions in terms
      of relatives' life.

PMID- 10965755
TI  - [Comparison of physical, psychological, and social resources and their effects on
      mental well-being between young-old and old-old Japanese elderly].
AB  - PURPOSES: We compared the availability of physical, psychological, and social
      resources, and effects of those resources on mental well-being both directly and
      as stress buffers between the young-old (the age of 65 to 74 years) and the old
      old (the age of 75 years and over) people. In addition, if there were a
      significant difference in level of mental well-being by the age categories, we
      examined whether the difference could be explained from the different amount of
      resources possessed by the age groups. METHODS: We utilized an effective sample
      of 923 young-old and 417 old-old persons excluding cases with missing variables,
      from 2,200 respondents of a national survey of Japanese adults aged 60 and over.
      This survey was conducted in 1987. While measure of physical resources included
      existence of chronic diseases and activities of daily living, psychological
      resources included self-esteem and locus of control. Social resources were
      measured by social support. The Center for Epidemiologic Scale-Depression (CES-D)
      was chosen as an indicator of mental well-being. RESULTS: 1. Although the old-old
      possessed a smaller amount of physical resources, they had almost the same amount
      of psychological and social resources as compared with the young-old respondents.
      2. There were few differences in the effects of those resources on mental well
      being between the young-old and the old-old. 3. Lower amount of physical resource
      was related to a lower level of well-being in the old-old more than in the young
      old. CONCLUSION: The old-old appear to possess similar psychological and social
      resources as the young-old, quantitatively, and in effects on successful
      adaptation. Lack of physical resources may be associated with a low level of
      mental well-being in the old-old.

PMID- 10965756
TI  - [Sociodemographic factors affecting access to and utilization of health care by
      Filipino workers in Japan].
AB  - Foreign workers face many difficulties in obtaining health care in Japan. To
      clarify the sociodemographic factors that determine health care access for
      foreign workers, qualitative and quantitative studies were conducted. The
      respondents of this study were Filipino workers, who are one of the major ethnic
      groups in Japan. Quantitative survey (N = 276) was performed by delivering
      questionnaires to attendants at mass at 12 churches in the Greater Tokyo Area. To
      obtain a clearer understanding of what factors are associated with health care
      access, logistic regression analysis was conducted. Independent variables were
      gender, age, length of stay in Japan, type of job in Japan, whether they sent
      money periodically to family, Japanese proficiency, whether they were uninsured,
      and whether they belonged to an informational and/or tangible network. The
      independent variables were standardized before the analysis to isolate the
      contribution of each variable. The logistic regression results indicate that
      having support from a network (either informational or tangible or both) has the
      largest contribution to the healthcare access (beta = .780, P < 0.01), followed
      by length of stay in Japan (beta = .534, P < 0.01) and being female (beta = .356,
      P < 0.05). There was no significant association between Japanese proficiency and
      health care access. This study indicates that providing a social support network
      is an effective method of helping foreign workers to overcome the obstacles
      preventing them from obtaining health care access. This applies particularly to
      women and to those who are new comers to Japan.

PMID- 10965757
TI  - [Health and lifestyle among school children in Tannan health center, Fukui
      Prefecture].

PMID- 10965758
TI  - [Genetic aspects of hereditary polyposis of the gastrointestinal tract].

PMID- 10965759
TI  - [Genetic abnormality of hereditary nonpolyposis colorectal cancer and implication
      of clinical application].

PMID- 10965760
TI  - [A case of amebic liver abscess ruptured into the stomach].

PMID- 10965761
TI  - [Paralytic ileus, pneumatosis cystoides intestinalis and pneumoperitoneum
      complicated with overlap syndrome (progressive systemic sclerosis and
      polymyositis): report of an autopsy case].

PMID- 10965762
TI  - [A case of biliary stenosis in polycystic liver improved by injection of
      minocycline hydrochloride to a hepatic cyst].

PMID- 10965764
TI  - [A case of congenital choledochal dilatation of type II in Alonso-Lej's
      classification].

PMID- 10965763
TI  - [Autoimmune hepatitis diagnosed by the opportunity of hepatitis a virus
      infection].

PMID- 10965765
TI  - [Marked improvement by corticosteroid therapy for tumor-forming pancreatitis with
      Sjogren's syndrome, a case study].

PMID- 10965767
TI  - []

PMID- 10965766
TI  - [A case of heterotopic pancreas in the liver with primary cholesterol
      hepatolithiasis].

PMID- 10965768
TI  - []

PMID- 10965769
TI  - The prevalence of delta virus infection in chronic liver disease in Egyptian
      children in comparison with some other countries.
AB  - BACKGROUND: Hepatitis Delta Virus (HDV) infection has a worldwide distribution.
      The aim of this study was to establish its prevalence in Egyptian children with
      chronic liver disease, and its role in the development and progress of hepatic
      illness. METHODS: A prospective study of 45 Egyptian children who had liver
      cirrhosis (n = 24) or chronic hepatitis (n = 21) was done. They were
      consecutively chosen. Their ages ranged from 2-15 years (median = 5). Serological
      studies were performed to detect the presence of hepatitis B surface antigen (HBs
      Ag) and HDV infection IgG antibody (IgG anti-HD). RESULTS: Anti-delta antibody
      (IgG anti-HD) was detected in only four children with hepatic cirrhosis and non
      of the chronic hepatitis, with an overall prevalence of 8.9% (4/45). Three of
      them (75%) were hepatitis B surface antigen (HBs Ag) negative. Significant
      statistical association between delta infection and the state of hepatic illness
      was detected (p < 0.05). Whereas HBs Ag was detected in 54% (13/24) of liver
      cirrhosis and 52% (11/21) of chronic hepatitis, with an overall prevalence of 53%
      (24/45). There was no statistically significant association between HBs Ag
      positivity and state of hepatic illness. CONCLUSIONS: The prevalence of HDV
      infection is 8.9% of Egyptian children with chronic liver disease. HDV infection
      in children is associated with advanced chronic liver disease.

PMID- 10965770
TI  - The clinical utility of serum uric acid measurements in pre-eclampsia and
      transient hypertension in pregnancy.
AB  - BACKGROUND: Our purpose was to evaluate the clinical utility of serum uric acid
      measurements in the hypertension diseases of pregnancy. METHODS: We identified
      286 women and categorized them into three diagnostic groups according to
      definitions of hypertensive diseases in pregnancy published by the National
      Working Group on Hypertension in Pregnancy: pre-eclampsia (94), transient
      hypertension (102) and normal (90). We compared the median uric acid
      concentration for each group and calculated the sensitivities and the
      specificities in diagnosing pre-eclampsia. The results were analyzed by the Mann
      Whitney test. RESULTS: Median serum uric acid values in the pre-eclamptic group,
      in the transient hypertension group and in the control group were 375 (262-536)
      mumol/L, 309 (214-387) mumol/L, 259 (143-339) mumol/L, respectively. Compared
      with normal, the median serum uric acid levels in women with pre-eclampsia or
      transient hypertension were significantly elevated. Differences in median serum
      uric acid concentrations between women with preeclampsia and with transient
      hypertension were statistically significant too. The prevalence of IUGR in the
      pre-eclamptic group and transient hypertension group was 65.9% and 29.4%,
      respectively. Sensitivity for serum uric acid levels of 339 mumol/L was 77.3% in
      the pre-eclamptic group and 32.3% in the transient hypertension group; the
      difference was statistically significant. Specificity was exactly the same in
      both groups (92%). CONCLUSIONS: Our data, in accordance with international
      literature, confirm the clinical utility of serum uric acid as a marker of pre
      eclampsia, but not of transient hypertension. Furthermore its high predictive
      value makes it possible to select a group of pre-eclamptic women with high risk
      for intrauterine growth retardation.

PMID- 10965771
TI  - Recurrent spontaneous abortion. Etiologic factors.
AB  - BACKGROUND: Spontaneous abortion is the most common complication of pregnancy. It
      may be unique, remaining random and having no consequences on the reproductive
      process, or it can repeat itself, starting a clinical picture known as recurrent
      spontaneous abortion or habitual abortion. The term of RSA syndrome is used to
      define the repetition of three or more consecutive abortions before the 24th
      week. METHODS: A population of 195 couples with recurrent spontaneous abortion
      were screened for genetic, metabolic, infective, morphological, endocrine and
      autoimmune factors. Eighty-five completed the investigation, 44 are being tested
      and 66 did not complete the diagnostic course. Causes of recurrent abortion were
      evaluated in relation to the period of abortion and number of embryo losses.
      RESULTS: Forty-six percent of patients who completed the investigation turned out
      to be sine causa, which is in accordance with the findings in literature.
      CONCLUSIONS: Couple with RSA require accurate counselling and it is fundamental
      to eliminate any pathologies that can be discovered so as to improve the
      likelihood of the pregnancy's reaching term.

PMID- 10965772
TI  - Beneficial effects of iloprost during experimentally induced hemorrhagic shock.
AB  - BACKGROUND: The aim of the study was to evaluate the efficacy of iloprost on
      myocardial insufficiency associated with hypovolemic shock in dogs. We designed
      the study as a controlled randomized study. METHODS: Sixteen mixed-breed dogs
      were included into the study and divided into two equal groups as the control and
      iloprost groups. Mean arterial pressure was reduced to 45 mmHg by withdrawing the
      arterial blood into citrated bags. The control group did not receive any drug but
      the other group received iloprost at a rate of 20 ng/kg/min by an infusion pump.
      Iloprost infusion was started 30 min after the blood pressure was reduced to 45
      mmHg. All measurements were made before removal of blood, 45 min after
      exsanguination and at 1 hour intervals for 3 hours. Left ventricular stroke work
      index was measured 72 hours after the study. The hemodynamic and biochemical
      parameters and blood gas analysis were obtained. RESULTS: After hemorrhage,
      cardiac index (CI) decreased significantly from 132 +/- 14 to 51 +/- 8 ml/kg/min
      in the control group and from 128 +/- 11 ml/kg/min to 47 +/- 13 ml/kg/min in the
      iloprost group, respectively but at the end of the third hour it was 81 +/- 8
      ml/kg/min in the control group and 105 +/- 6 ml/kg/min in the iloprost group (p <
      0.05). Tumor necrosis factor-alpha (TNF alpha) was 41 +/- 8 pg/ml in the control
      group and 18 +/- 6 in the iloprost group 3 hours after bleeding (p < 0.05). Tumor
      necrosis factor-alpha concentration was significantly higher in the control group
      than in the iloprost group. There was no significant difference in pH between the
      groups but actual bicarbonate concentrations were different between the groups (p
      < 0.05). At the end of the third hour total body oxygen consumption was 105 +/-
      11 ml/min in the control group and 132 +/- 12 ml/min in the iloprost group (p <
      0.05). Oxygen delivery 3 hours after hemorrhage was 201 +/- 19 ml/min in the
      control group and 252 +/- 24 ml/min in the iloprost group (p > 0.05). Left
      ventricular stroke work index was higher in the iloprost group (p < 0.05).
      CONCLUSIONS: Hemorrhagic shock causes tumor necrosis factor-alpha release which
      may lead to multiple organ failure. Organ dysfunction still persists even after
      the appropriate treatment. Iloprost attenuates the release of tumor necrosis
      factor-alpha which may improve the adverse effects of hemorrhagic shock.

PMID- 10965774
TI  - Effects of a short-term hypoenergetic diet on morphofunctional left ventricular
      parameters in centrally obese subjects. An echocardiographic study.
AB  - BACKGROUND: We aimed to study centrally obese subjects without other diseases, to
      establish whether a short-term hypoenergetic balanced regimen is able to
      positively modify left ventricular (LV) patterns. METHODS: We studied 32 obese
      subjects (out of 52 recruited for this study) with central fat distribution and
      without associated diseases. Each subject had undergone a moderately
      hypoenergetic diet for a four-month follow-up period and had a regular loss in
      weight. Some relevant clinical and echocardiographic parameters were evaluated.
      Baseline data and those evaluated at the end of the follow-up period were used
      for outcome analysis. RESULTS: We found a considerable reduction in LV mass and
      other LV structural parameters including relative wall thickness (RWT). Moreover,
      we found an improvement of both LV ejection fraction and filling parameters. As
      regards the relation ship between parameter changes, LV mass was correlated to LV
      internal diameter and mainly to LV wall thickness. LV mass change was also
      correlated to a reduction of diastolic BP and RWT. Only improvements in LV
      filling were correlated to WHR reduction. None of the changes in cardiac
      variables resulted significantly correlated to BMI change. Other interesting
      correlations are reported in the text. CONCLUSIONS: Our study points out that
      improvements in LV structure and function are rapidly possible with a moderately
      hypoenergetic regimen in obese otherwise healthy subjects. The main changes were
      those in LV wall thickness even if a more complex cardiovascular adjustment was
      recognised. All this could be very important to possibly prevent future
      cardiovascular events (including heart failure), so largely linked to obesity of
      central type.

PMID- 10965773
TI  - Iodinated contrast media induced oxidative stress status in patients undergoing
      urography.
AB  - BACKGROUND: The present investigation is an extension of our earlier work on
      oxidative stress in a number of clinical situations and awareness of potential
      toxicity of contrast media. It was of interest to understand the relative safety
      (in terms of balance between oxidants/antioxidants) of the usage of iodinated
      contrast media in urography. METHODS: Alterations in serum levels of oxidant
      lipid peroxidation and product malondialdehyde (MDA) and components of anti
      oxidant have been studied in 125 patients (with renal calculus disease) to
      undergo intravenous urographic procedure before and 3 hours following intravenous
      administration of Trivideo-400 (Iothalmate Sodium 40 ml: 18 gm Iodine) and
      results of serum levels of MDA (nmol/ml), SOD (mu/ml), Vit-C and Vit-E (mg/dl)
      were also compared with 135 appropriately age matched controls. RESULTS: The
      salient features of present investigation indicated definite pattern viz.
      Significant rise in serum levels of oxidant MDA (4.35 +/- 2.05) and fall in SOD
      (3.04 +/- 1.04), Vit-C (0.55 +/- 0.17), Vit-E (0.67 +/- 0.20) in patients at pre
      IVU stage in comparison with those of controls viz MDA (4.35 +/- 2.05), SOD (3.77
      +/- 1.55), Vit-C (0.71 +/- 0.25) and Vit-E (0.80 +/- 0.30). There occurred
      further elevation in serum levels of MDA (5.28 +/- 2.48) and fall in SOD (3.07 +/
      0.97), Vit-C (0.52 +/- 0.16), Vit-E (0.66 +/- 0.19) showing no significant
      alterations 3 hours following intravenous IVU procedure. CONCLUSIONS: It is
      concluded that contrast media induced changes did remain within tolerable
      physiological limits and no significant changes in anti-oxidant components Vit-E
      and SOD were suggestive of relative safety of iodinated contrast media usage.

PMID- 10965775
TI  - Life habits and cardiovascular risk in a group of bank employees in Rome.
AB  - BACKGROUND: For the past thirty years, many countries, especially the USA, have
      been performing clinical and laboratory studies to establish the most prominent
      disease risk factors, in particular those involved in cardiovascular diseases.
      The main aim of these studies is to reduce disease related risks by intervening
      at an early age. METHODS: We studied 305 patients, 198 males and 107 females, all
      employees in Rome, mean age 40.8 years (+/- 8.22), enrolled from September 1988
      to December 1989. We measured the main anthropometric parameters and performed
      otolaryngologic and ocular examination, a telecardiogram and an EKG; the
      following analyses were performed: hemochrome, ESR uric acid, azotemia, glycemia,
      AST, ALT, gamma GT, bilirubinemia, proteic electrophoresis, triglyceridemia,
      total cholesterolemia, HDL cholesterolemia, creatinine, urine examination, Pap
      Test for women. Lifestyle habits that might be considered cardiovascular disease
      risk factors were considered and hygienic eating habits were suggested. Seven
      years later, in 1997, 100 of these patients were randomly selected (51 man and 49
      women) and underwent the same clinical and laboratory tests as before. RESULTS:
      The results suggest a deep correlation between lifestyles and the increase of
      some cardiovascular risk factors. CONCLUSIONS: The authors believe that this
      study can be of some help in guiding future preventive medicine interventions
      that may be carried out on this population sample.

PMID- 10965776
TI  - Tourette's syndrome in children: neurological, neuropsychological and psychiatric
      issues.
AB  - The interplay between neurologic, neuropsychologic and psychiatric features makes
      Tourette's syndrome (TS) a paradigmatic model for neuropsychiatric disorders. The
      aim of this paper is to review this complex interplay of clinical features. After
      a survey of some epidemiological studies, the natural history of neurological,
      behavioral and psychological characteristics of the syndrome is described. The
      problem of high psychiatric comorbidity, firstly with obsessive-compulsive
      disorder and attention deficit-hyperactivity disorder, is discussed.
      Neuropsychological features of TS are considered, as they can negatively affect
      the quality of life of affected patients. Considerations on treatment,
      pharmacologic as well as educational and psychotherapeutic, conclude this review.

PMID- 10965777
TI  - Hepatocellular carcinoma in a non-cirrhotic liver. Two case reports and
      literature review.
AB  - Hepatocellular carcinoma (HCC) is closely associated with cirrhosis, but it also
      develops, although much less frequently, in a non-cirrhotic liver. It is
      suspected that hepatocellular carcinoma has a different etiology when associated
      and not associated with chronic liver disease. We report two cases of patients
      with hepatocellular carcinoma that developed in a non-cirrhotic liver. In the
      first case we describe an incidental liver nodular lesion containing multiple
      foci of HCC including pseudogland or trabecular formation and areas of sclerosis.
      The non-cancerous parenchyma of the liver was histologically unremarkable except
      for mild fatty changes of hepatocytes and minimal dysplasia. The second case
      describes a combined hepatocellular carcinoma and cholangiocellular carcinoma
      (CCC) (mixed carcinoma) in a patient who was serologically negative for both
      hepatitis B and C viruses. The adjacent liver parenchyma showed mild piecemeal
      necrosis and mild lobular activity compatible with chronic viral hepatitis, but
      cirrhosis was not established. This case appears to indicate that mixed type
      carcinoma can develop in a non-cirrhotic liver, with CCC being far more dominant
      than HCC; such a finding is extremely unusual, based on previously published
      reports.

PMID- 10965778
TI  - EDTA-dependent pseudothrombocytopenia in a case of liver cirrhosis.
AB  - Pseudothrombocytopenia (PTCP) is the consequence of an EDTA-activated platelet
      agglutination, resulting in a spuriously low platelet count. We report the case
      of a 54-year-old man with EDTA-dependent PTCP associated with liver cirrhosis. He
      couldn't undergo endoscopic examination and dental care for two years because of
      a previous diagnosis of severe thrombocytopenia secondary to liver cirrhosis.
      Lack of PTCP recognition may lead the physician to misdiagnosis and mismanagement
      of the patient.

PMID- 10965779
TI  - Contribution to the choice of therapy in abdominal pregnancy.
AB  - The goal of our study was to offer our contribution to the selection of the most
      suitable therapy to treat abdominal pregnancy. We discuss three patients affected
      with this pathology, which was diagnosed early by laparoscopy. The patients were
      treated with 50 mg/m2 of methotrexate administered intravenously. The abdominal
      pregnancy was terminated in all three patients. Since the outcome involved
      termination of the pregnancy, it is important to emphasize that methotrexate
      therapy, must be considered elective. Operative laparoscopy can be limited only
      to cases in which the ovum has not become implanted in the intestinal interstices
      and is not near sites susceptible to complications.

PMID- 10965780
TI  - Diagnosis controversies for adrenal ganglioneuroma.
AB  - The authors report a case of adrenal ganglioneuroma which was incidentally
      diagnosed performing preoperative examination for a sigmoid carcinoma. The
      authors took this finding as a starting point to underline the rarity of this
      condition and its chance discovery, this being due to the rare presence of signs
      and symptoms and its frequent association with other synchronous neoplasms; all
      this makes differential diagnosis rather difficult.

PMID- 10965781
TI  - State-specific prevalence of selected health behaviors, by race and ethnicity-
      Behavioral Risk Factor Surveillance System, 1997.
AB  - PROBLEM/CONDITION: In the United States, disparities in risks for chronic disease
      (e.g., diabetes, cardiovascular disease, and cancer) and injury exist among
      racial and ethnic groups. This report summarizes findings from the 1997
      Behavioral Risk Factor Surveillance System (BRFSS) of the distribution of access
      to health care, health-status indicators, health-risk behaviors, and use of
      clinical preventive services across five racial and ethnic groups (i.e., whites,
      blacks, Hispanics, American Indians or Alaska Natives, and Asians or Pacific
      Islanders) and by state. REPORTING PERIOD COVERED: 1997. DESCRIPTION OF SYSTEM:
      The BRFSS is a state-based telephone survey of the civilian,
      noninstitutionalized, adult (i.e., persons aged > or = 18 years) population. In
      1997, all 50 states, the District of Columbia, and Puerto Rico participated in
      the BRFSS. RESULTS: Variations in risk for chronic disease and injury among
      racial and ethnic groups exist both within states and across states. For example,
      in Arizona, 11.0% of whites, 26.2% of Hispanics, and 50.5% of American Indians or
      Alaska Natives reported having no health insurance. Across states, the median
      percentage of adults who reported not having this insurance ranged from 10.8% for
      whites to 24.5% for American Indians or Alaska Natives. Other findings are as
      follows. Blacks, Hispanics, American Indians or Alaska Natives, and Asians or
      Pacific Islanders were more likely than whites to report poor access to health
      care (i.e., no health-care coverage and cost as a barrier to obtaining health
      care). Blacks, Hispanics, and American Indians or Alaska Natives were more likely
      than whites and Asians or Pacific Islanders to report fair or poor health status,
      obesity, diabetes, and no leisure-time physical activity. Blacks were
      substantially more likely than other racial or ethnic groups to report high blood
      pressure. Among all groups, American Indians or Alaska Natives were the most
      likely to report cigarette smoking. Except for Asians or Pacific Islanders, the
      median percentage of adults who reported not always wearing a safety belt while
      driving or riding in a car was > or = 30%. The Papanicolaou test was the most
      commonly reported screening measure: > or = 81% of white, black, and Hispanic
      women with an intact uterine cervix reported having had one in the past 3 years.
      Among white, black, and Hispanic women aged > or = 50 years, > or = 63% reported
      having had a mammogram in the past 2 years. Approximately two thirds of white,
      black, and Hispanic women aged > or = 50 years reported having had both a
      mammogram and a clinical breast examination in the past 2 years; this behavior
      was least common among Hispanics and most common among blacks. Screening for
      colorectal cancer was low among whites, blacks, and Hispanics aged > or = 50
      years: in each racial or ethnic group, < or = 20% reported having used a home-kit
      blood stool test in the past year, and < or = 30% reported having had a
      sigmoidoscopy within the last 5 years. INTERPRETATION: Differences in median
      percentages between racial and ethnic groups, as well as between states within
      each racial and ethnic group, are likely mediated by various factors. According
      to published literature, socioeconomic factors (e.g., age distribution,
      educational attainment, employment status, and poverty), lifestyle behaviors
      (e.g., lack of physical activity, alcohol intake, and cigarette smoking), aspects
      of the social environment (e.g., educational and economic opportunities,
      neighborhood and work conditions, and state and local laws enacted to discourage
      high-risk behaviors), and factors affecting the health-care system (e.g., access
      to health care, and cost and availability of screening for diseases and health
      risk factors) may be associated with these differences. ACTION TAKEN: States will
      continue to use the BRFSS to collect information about health-risk behaviors
      among various racial and ethnic groups. (ABSTRACT TRUNCATED)

PMID- 10965782
TI  - Current trends in the management of chronic myelogenous leukemia.
AB  - The management of chronic myelogenous leukemia (CML) has become complex due to
      the availability of improved diagnostic procedures and life-prolonging or even
      curative treatment strategies that are more successful the earlier they are
      applied in the course of the disease. This is true for allogeneic bone-marrow
      transplantation, treatment with interferon alpha (IFN) and Philadelphia-negative
      stem-cell collections for autografting. Outcome differs according to risk
      profiles of patients at diagnosis. In addition, molecular techniques for the
      detection of the BCR-ABL fusion gene or its products, such as the reverse
      transcriptase polymerase chain reaction (PCR), Southern blot analysis, or
      fluorescence in situ hybridization, facilitate accurate diagnosis and the
      monitoring of residual disease. They allow the individualization of treatment
      such as early infusion of donor lymphocytes if molecular relapse is detected
      after allografting, or discontinuation of IFN in the presence of very low BCR-ABL
      transcript levels). The availability of real-time PCR devices further improves
      and accelerates the diagnosis and monitoring of residual disease. This article
      addresses recent developments in drug therapy and allografting, including
      treatment intensification with low-dose ara C or intensive chemotherapy followed
      by autografting, introduction of new drugs (such as homoharringtonine or tyrosine
      kinase inhibitor STI571), progress with unrelated donor transplantations, use of
      peripheral blood stem cells for allografting, and transplantation without
      myeloablative conditioning. Tradeoffs between the treatment options will be
      discussed in the context of the evidence-based guidelines for treating CML, as
      recently published by the American Society of Hematology. Finally, the new
      competence network on acute and chronic leukemias will be introduced.

PMID- 10965783
TI  - Culture requirements for induction of dendritic cell differentiation in acute
      myeloid leukemia.
AB  - Peripheral blood mononuclear cells (PBMCs) from 15 newly diagnosed acute myeloid
      leukemia (AML) patients were cultured in fetal calf serum-free media supplemented
      with either granulocyte/macrophage-colony stimulating factor (GM-CSF),
      interleukin (IL)-4 and tumor necrosis factor alpha (TNFalpha), or GM-CSF, stem
      cell factor (SCF), TNFalpha and transforming growth factor beta (TGFbeta) in
      order to generate leukemia-derived dendritic cells (DCs). Cultured cells were
      analyzed by flow cytometry with respect to DC-associated surface molecules (CD1a,
      CD83, CD40, CD80, CD86, HLA-DR) when they showed significant DC morphology in
      culture (14 cases). After cultivation, neo-expression or upregulation of CD1a
      antigen was found in 8 samples, CD83 in 2, CD40 in 14, CD80 in 7, and CD86 in 9.
      Twelve of 14 AMLs, in which DC morphology could be induced upon cultivation,
      showed upregulation of at least 2 DC-associated molecules. For induction of DC
      differentiation. GM-CSF, IL-4 plus TNFalpha was superior in 11 cases, and better
      results were obtained with GM-CSF, SCF, TNFalpha plus TGFbeta in 3 cases. In 7 of
      14 samples tested, a marked increase of the T-cell stimulatory capacity could be
      demonstrated in the allogeneic mixed lymphocyte reaction. The leukemic origin of
      in vitro-generated DCs was demonstrated by fluorescence in situ hybridization in
      a patient with translocation t(15;17). Our results suggest that the use of
      different culture conditions may extend the number of AML patients in which a
      differentiation towards the DC lineage can be induced in vitro.

PMID- 10965784
TI  - Cytokines can reduce clonal, CD34-positive cells in acute myeloid leukemia in
      vitro.
AB  - We studied the influence of cytokine mixes on the survival of acute myeloid
      leukemia (AML) bone-marrow (BM) cells in a 14-day culture assay in vitro.
      Southern-blot analysis using a panel of different probes in combination with
      densitometry and flow cytometry were used to detect and compare the amount of
      clonal or CD34-positive BM cells before and after the culturing procedure. A
      significant reduction of CD34-positive cells after incubation with a cytokine mix
      [interleukin (IL)-1beta, IL-3, IL-6, stem cell factor (SCF), erythropoietin (EP)
      with granulocyte macrophage/colony-stimulating factor (GM-CSF, Cytok1) could be
      achieved in all 16 cases with a CD34-positive blast phenotype studied at
      diagnosis (P<0.001), in 3 of 10 cases at relapse, and in 8 of 18 cases in
      complete remission. In healthy donors, an increase of CD34-positive cells was
      demonstrated in 5 of 5 samples. A reduction of clonal DNA through incubation with
      Cytok1 was achieved in 5 of 5 (100%) cases studied at diagnosis, in 1 of 4 (25%)
      cases at relapse, and in 7 of 9 cases (78%) in complete remission. Cytokine
      cocktails with GM-CSF (Cytok1) were more efficient in reducing (clonal) CD34
      positive cells than cocktails without GM-CSF (Cytok2). AML patients at diagnosis
      and in complete remission had a better survival probability if their CD34
      positive or clonal cells could be reduced in vitro by cytokine cultivation
      (P<0.05). Vitality of BM cells was not influenced by 14-day cytokine treatment;
      however, the total cell count could be increased by Cytok1 and Cytok2 by 55-174%,
      but not by the control medium. Our data show that: (1) clonal cell populations
      can be regularly detected at diagnosis, during complete remission, and at
      relapse; (2) CD34-positive cells in AML can be demonstrated to be clonal, gene
      rearranged cells; (3) incubation of AML BM-cells with Cytokl leads to a reduction
      of the CD34-positive, clonal cell load in all cases at diagnosis and in 78% of
      the cases in complete remission of AML, but in only 25% of the cases at relapse;
      (4) in all healthy BM samples, proportions of 'healthy' CD34-positive cells were
      increased. Moreover, absolute cell counts were increased by cytokine incubation
      of cells obtained at diagnosis, relapse, or complete remission of AML and from
      healthy donors indicating a selective stimulation of healthy, but not of leukemic
      CD34-positive cells; (5) cytokine cocktails containing GM-CSF are more efficient
      in reducing leukemic cells than cocktails without GM-CSF; and (6) in vitro
      reactivity of clonal or CD34-positive BM cells against Cytokl has clinical
      relevance. We conclude, that Southern-blot analysis and flow cytometry are
      suitable methods to detect and quantify leukemic disease and to distinguish
      between clonal or non-clonal CD34-positive cells. The ex vivo or clinical
      application of specific combinations of cytokines might be a feasible and
      successful application of immunotherapy in AML that merits further
      investigations.

PMID- 10965785
TI  - Low curative potential of bone marrow transplantation for highly aggressive acute
      myelogenous leukemia with inversioin inv (3)(q21q26) or homologous translocation
      t(3;3) (q21;q26).
AB  - Structural rearrangements of the long arm of chromosome 3 involving bands 3q21
      and 3q26 and leading either to a paracentric inversion inv (3)(q21q26) or a
      translocation between both homologous chromosomes--t(3;3)(q21q26)-- have been
      reported in patients with acute myelogenous leukemia (AML), myelodysplastic
      syndromes, myeloproliferative disorders, and chronic myelogenous leukemia in
      blast crisis. We describe three patients with de novo AML with these structural
      abnormalities who received multiple courses of conventional chemotherapy followed
      by unrelated donor (n=2) and autologous (n = 1) bone marrow transplantation
      (BMT). All three patients had early relapse: patients 1 and 2 had relapse 69 days
      and 306 days after BMT, respectively, and patient 3 immediately after autologous
      BMT. Despite further chemotherapy, they died without achieving another remission.
      These findings, together with other recorded similar cases, show that AML with
      structural abnormalities of the long arm of chromosome 3 as described has an
      extremely poor prognosis even with the most potent anti-leukemic treatment
      modalities.

PMID- 10965786
TI  - B-cell lymphoma-associated hemophagocytic syndrome: clinicopathological
      characteristics.
AB  - Seven patients with peripheral B-cell lymphoma associated with hemophagocytic
      syndrome are reported. In all cases, the histologic subtype was diffuse large B
      cell lymphoma. Hemophagocytic features were noted in the bone marrow with
      lymphomatous infiltration. Hemophagocytic syndrome occurred with presentation of
      the lymphoma and was characterized by high fever, cytopenias, and elevated levels
      of lactate dehydrogenase, ferritin, C-reactive protein, and cytokines [interferon
      gamma, macrophage colony-stimulating factor, soluble interleukin (sIL)-2R, and IL
      6] without evidence of infection. The phenotypes of lymphomas were suspected
      CD19+, CD20+, S-Ig+, CD10-, and coexpression of CD5 in some cases. Flow
      cytometric analysis showed a low CD4/CD8 ratio in peripheral blood and bone
      marrow. We suggest that the pathogenesis of hemophagocytic syndrome is
      hypercytokinemia induced by a proliferation of reactive CD8+ T cells. Previous
      reports of B-cell lymphoma with hemophagocytic syndrome demonstrated similar
      clinical manifestations and poor prognoses. The invasion patterns of these
      diffuse large B-cell lymphomas with hemophagocytosis may be classified into three
      groups: microscopic lymph-node involvement type, gross lymph-node involvement
      type, and splenic lymphoma type. Although hemophagocytic syndromes have been
      reported to be associated with T-cell lymphomas, our results indicate an
      association with diffuse large B-cell lymphoma.

PMID- 10965787
TI  - Successful treatment of B-cell lymphoma associated with hemophagocytic syndrome
      using autologous peripheral blood CD34 positive cell transplantation followed by
      induction of autologous graft-versus-host disease.
AB  - A 56-year-old man who presented with persistent high fever and abdominal pain was
      diagnosed as having a B-cell lymphoma associated with hemophagocytic syndrome (B
      LAHS). As post-remission therapy, the patient was treated with high-dose
      chemoradiotherapy followed by infusion of autologous CD34+ cells that had been
      isolated from the peripheral blood buffy coat. Cyclosporin and interferon (IFN)
      gamma were administered to induce autologous graft-versus-host disease (GVHD).
      Hematopoietic recovery promptly occurred and skin GVHD developed on day 26 after
      CD34+ cell transplantation. The patient has been in complete remission without
      therapy for 20 months since transplant. Autologous CD34+ cell transplantation in
      combination with induction of autologous GVHD may be efficacious in obtaining a
      cure for B-LAHS.

PMID- 10965788
TI  - Progressive multifocal leukoencephalopathy following oral fludarabine treatment
      of chronic lymphocytic leukemia.
AB  - Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating
      disorder of the central nervous system usually affecting immunocompromised
      individuals and is due to infection of the oligodendrocytes by the JC virus. A
      case of PML in a chronic lymphocytic leukemia (CLL) patient treated with
      fludarabine is reported, representing the second such instance in which the
      diagnosis of the neurological disorder was established by brain biopsy. A 61-year
      old man with a 14-year history of B-cell type CLL, for which he had received
      chlorambucil therapy 10 years earlier, developed progressive paresis of both left
      extremities at 7 months of receiving low doses of oral fludarabine, when his CD4
      count has decreased to 0.08 x 10(9)/l. Cranial magnetic resonance imaging
      revealed a subcortical focal lesion at the right precentral gyrus and a focal
      lesion at the right thalamus, and a stereotactic brain biopsy showed pathological
      findings consistent with PML, namely severe myelin breakdown, reactive
      astrocytosis, and abnormal, huge glial cells with large bizarre nuclei showing
      granular basophilic inclusions, whereas the presence of the JC virus was
      demonstrated by in situ hybridization. The present case, in addition to a few
      previously reported, calls attention to the possibility that severe neurological
      side effects can be associated with the immunosuppression provoked by the use of
      fludarabine in CLL patients.

PMID- 10965790
TI  - Specific cutaneous infiltrate caused by Staphylococcus aureus in a patient with
      chronic myelomonocytic leukemia.
AB  - We present a patient with chronic myelomonocytic leukemia who showed disseminated
      papules and nodules. Arguments in favor of leukemia cutis are the clinical
      appearance, the cyclic pattern with which the lesions appeared and disappeared,
      and the histologic features. The lesions reproducibly responded to treatment with
      antibiotics given for a Staphylococcus aureus infection. We speculate that at
      least in some patients, leukemic cells are recruited in the skin because of local
      infection and do not merely reflect autonomous growth but an inflammatory
      response.

PMID- 10965789
TI  - A case of chronic myeloid leukemia with minor bcr-abl transcript following
      fluorouracil therapy for esophageal carcinoma.
AB  - We report here a very rare case of chronic myeloid leukemia (CML) with a minor
      bcr-abl transcript, which developed following long-term chemotherapy with
      fluorouracil for esophageal carcinoma. A 64-year-old male patient was diagnosed
      with CML. Four years earlier, he had suffered from esophageal carcinoma, which
      was treated by surgical resection followed by oral administration of fluorouracil
      (200 mg/day) for 4 years. Molecular analysis of his Philadelphia chromosome (Ph)
      using reverse-transcriptase polymerase chain reaction (RT-PCR) and subsequent
      sequencing revealed a minor bcr-abl transcript. The clinical course of this
      patient was aggressive with a short chronic phase of CML. This is the first
      reported case of secondary CML with a minor bcr-abl transcript.

PMID- 10965791
TI  - Extensive calcification of the pericardium in a patient with primary amyloidosis.

PMID- 10965792
TI  - A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's
      disease, progressive supranuclear palsy and Pick's disease.
AB  - Neurofibrillary tangles (NFT), one of the histopathological hallmarks of
      Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), and Pick
      bodies in Pick's disease (PiD) are composed of microtubule-associated protein
      tau, which is the product of alternative splicing of a gene on chromosome 17.
      Alternative expression of exon 10 leads to formation of three- or four-repeat tau
      isoforms. To study the differential expression of exon 10, we performed double
      labeling immunohistochemistry of the hippocampal formation in nine AD, four PSP
      and three PiD cases. Cryostat sections were processed with and without formic
      acid (FA) treatment, and double-stained with anti-tau (Alz-50 or PHF-1) or anti
      amyloid P component antibodies and one of two specific anti-exon 10 antibodies (E
      10). The effect of proteinase-K treatment was also evaluated. The results suggest
      the following. First, in AD, E-10 immunoreactivity is present in most
      intracellular NFT, but not in most dystrophic neurites and neuropil threads,
      suggesting differential expression of tau isoforms in specific cellular domains.
      Second, in AD, E-10 immunoreactivity is lost or blocked in most extracellular
      NFT, possibly due to proteolysis. Third, in PSP, E-10 immunoreactivity is hidden
      or blocked in NFT and tau-positive glial inclusions, but FA treatment exposes the
      epitope consistent with the hypothesis that PSP inclusions contain four-repeat
      tau. Fourth, E-10 immunoreactivity is present in dentate fascia NFT in AD and
      PSP, but not in Pick bodies in the dentate fascia or other areas. The results
      suggest that expression of exon 10 in tau is specific for cellular domains in a
      disease-specific manner.

PMID- 10965793
TI  - Histopathological analysis of four autopsy cases of HTLV-I-associated
      myelopathy/tropical spastic paraparesis: inflammatory changes occur
      simultaneously in the entire central nervous system.
AB  - Although brain lesions have been described in some cases with HTLV-I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the
      nature of brain lesion and its relation to the spinal cord lesion. In the present
      study, we performed histopathological analysis of the brain and the spinal cord
      of four autopsied cases with HAM/TSP to clarify the relationship between the
      brain and the spinal cord lesions. In two cases with active-chronic inflammation
      in the spinal cord, perivascular inflammatory infiltration was also seen in the
      brain, and the composition of cell subsets was similar both in the spinal cord
      and in the brain. No active inflammatory change was seen in the brain in two
      cases with inactive-chronic spinal cord lesions. Inflamed vessels were
      distributed mainly in the deep white matter and in the area between cerebral
      cortex and white matter of the brain. In the spinal cord inflamed vessels were
      mainly seen in the bilateral lateral and the ventral posterior columns.
      Parenchymal infiltration was diffused in the spinal cord but very sparse in the
      brain, suggesting the importance of parenchymal infiltration in the destruction
      of tissues. These results suggest that inflammatory changes occurred
      simultaneously in the spinal cord and in the brain, and that distribution of
      inflamed vessels closely correlated with the characteristics of vascular
      architecture of the brain and the spinal cord, which lead to a slow blood flow.
      This study may help promote a better understanding of the pathogenesis of
      HAM/TSP.

PMID- 10965794
TI  - The effects of different training programs on the trapezius muscle of women with
      work-related neck and shoulder myalgia.
AB  - The aim of this study was to examine the effects of training on the structural
      characteristics of the trapezius muscle in women with work-related trapezius
      myalgia. Muscle biopsies were taken before and after 10 weeks of three different
      training programs (strength, endurance and coordination). Enzyme
      immunohistochemical analysis was performed to assess muscle fibre types, fibre
      area, capillary supply and cytochrome c oxidase (COX) activity. There was an
      increase in the proportion of type IIA fibres in strength trained group (P <
      0.05). Strength training elicited a preferential increase in the area of type II
      fibres (P < 0.05); both strength and endurance programs induced an increase in
      the number of capillaries around type I and IIA muscle fibres. Finally, all
      training programs induced a decrease in the proportion of COX-negative fibres. In
      conclusion, the trapezius muscle of women with neck and shoulder myalgia is
      characterised by a great potential of adaptation to physical exercise over a
      period of 10 weeks. The significant changes in the number of capillaries and the
      specific changes induced by training at the level of muscle fibres might well
      explain the improvement of muscle function.

PMID- 10965795
TI  - Evolution of Alzheimer's disease-related cytoskeletal changes in the basal
      nucleus of Meynert.
AB  - This study examines the evolution of Alzheimer's disease (AD)-related pathology
      in a subcortical predilection site, the basal nucleus of Meynert (bnM), which is
      a major source of cortical cholinergic innervation. Brains of 51 autopsy cases
      were studied using silver techniques and immunostaining for tau-associated
      neurofibrillary pathology and for amyloid beta protein (Abeta) deposits. All
      cases are classified according to a procedure permitting differentiation of six
      stages of AD-related neurofibrillary changes in the cerebral cortex. Initial
      cytoskeletal abnormalities in the bnM are already noted in stage I of cortical
      neurofibrillary changes. The gradual development of the neurofibrillary pathology
      in the bnM parallels the progression of the AD-related stages in the cerebral
      cortex. A variety of morphologically distinguishable cytoskeletal alterations are
      observed in large nerve cells which predominate in the bnM. Based on these
      cellular alterations, a sequence of cytoskeletal deterioration is proposed.
      Initially, the abnormal tau protein is distributed diffusely throughout the cell
      body and the neuronal processes. Subsequently, it aggregates to form a
      neurofibrillary tangle, which appears as a spherical somatic inclusion. The cell
      processes gradually become fragmented. Finally the parent cell dies, leaving
      behind an extraneuronal "ghost tangle". With regard to the cortical stages of AD
      related neurofibrillary changes, the initial forms of cytoskeletal changes in the
      bnM predominate in the transentorhinal AD stages (I and II), while "ghost
      tangles" preferentially occur in the neocortical stages (V and VI). The
      considerable morphological diversity of cytoskeletal alterations is typical of
      stages III and IV. These results indicate that individual neurons of the bnM
      enter the sequence of cytoskeletal deterioration at different times.

PMID- 10965796
TI  - Fragmentation of the Golgi apparatus of the ballooned neurons in patients with
      corticobasal degeneration and Creutzfeldt-Jakob disease.
AB  - We investigated immunohistologically the Golgi apparatus (GA) and the trans-Golgi
      network (TGN) of the cortical ballooned neurons (BNs) in two patients with
      corticobasal degeneration and in five with Creutzfeldt-Jakob disease. We observed
      that the BNs showed fragmentation of the GA and the TGN, accompanied by a
      reduction in the number of fragmented Golgi elements and by a unique perinuclear
      distribution. This is the first report of the abnormalities of GA in cortical
      BNs. These findings suggests that the GA and the TGN may play some roles in the
      BN formation.

PMID- 10965797
TI  - Nonoxidative protein glycation is implicated in familial amyotrophic lateral
      sclerosis with superoxide dismutase-1 mutation.
AB  - To assess a role for oxidative stress in the pathogenesis of amyotrophic lateral
      sclerosis (ALS), we analyzed the immunohistochemical localization of 8-hydroxy2'
      deoxyguanosine (OHdG) as a nucleic acid oxidation product, acrolein-protein
      adduct and 4-hydroxy-2-nonenal (HNE)-protein adduct as lipid peroxidation
      products, Nepsiloncarboxymethyl-lysine (CML) as a lipid peroxidation or protein
      glycoxidation product, pentosidine as a protein glycoxidation product, and
      imidazolone and pyrraline as nonoxidative protein glycation products in the
      spinal cord of three familial ALS patients with superoxide dismutase(SOD 1) A4V
      mutation, six sporadic ALS patients, and six age-matched control individuals. The
      spinal cord sections of the control cases did not show any distinct
      immunoreactivities for these examined products. In the familial ALS cases,
      intense immunoreactivities for pyrraline and CML were confined to the
      characteristic Lewy body-like hyaline inclusions, and imidazolone
      immunoreactivity was located in the cytoplasm of the residual motor neurons. No
      significant immunoreactivities for other examined products were detected in the
      familial ALS spinal cords. In the sporadic ALS cases, intense immunoreactivities
      for pentosidine, CML and HNE-protein adduct were seen in the cytoplasm of the
      degenerated motor neurons, and OHdG immunoreactivity was located in the cell
      nuclei of the residual neurons and glial cells. The present results indicate that
      oxidative reactions are involved in the disease processes of sporadic ALS, while
      there is no evidence for increased oxidative damage except for CML deposition in
      the familial ALS spinal cords. Furthermore, it is likely that the accumulation of
      pyrraline and imidazolone supports a nonoxidative mechanism in SOD1-related motor
      neuron degeneration.

PMID- 10965798
TI  - Alpha-synuclein-immunoreactive cortical Lewy bodies are associated with cognitive
      impairment in Parkinson's disease.
AB  - Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB)
      degeneration and Alzheimer's disease (AD) type changes in 45 patients with
      Parkinson's disease (PD). For detection of LBs, the brain areas were stained with
      an antibody against alpha-synuclein. The extent of neuropathological lesions was
      investigated in relation to cognitive dysfunction and apolipoprotein E (apoE)
      epsilon4 allele dosage. At least one cortical LB was found in 95% of cases
      (43/45). Furthermore, 40% of cases (18/45) had histological findings of definite
      AD (CERAD class C). Those PD cases with the apoE epsilon4 allele had a
      significantly greater number of cortical LBs than those without the apoE epsilon4
      allele, but this was statistically significant only in precentral, angular and
      temporal gyri. The LB density correlated better with the number of plaques than
      with the density of tangles. The number of LBs in several cortical areas
      correlated significantly with the cognitive impairment. In stepwise linear
      regression analysis, the number of LBs in the cingulate gyrus and the amount of
      tangles in the temporal cortex remained statistically significant. When the CERAD
      class C was excluded, the correlation between cognitive decline and the number of
      LBs in cortical areas became even more pronounced. A stepwise linear regression
      analysis in these cases found the number of LBs in the frontal gyrus to be the
      statistically most significant predictor of cognitive impairment. This study
      shows, for the first time, that in PD, alpha-synuclein-positive cortical LBs are
      associated with cognitive impairment independent of AD-type pathology.

PMID- 10965799
TI  - Emerin presence in platelets.
AB  - Emerin is an almost ubiquitous protein which is abnormal in X-linked Emery
      Dreifuss muscular dystrophy (EMD), a syndrome characterized by muscle weakness,
      joint contractures and cardiac arrhythmia. Emerin is localized in the cells at
      the nuclear rim and its function is still unknown. In some models, emerin has
      also been described in the cytoplasm; however, its presence outside the nucleus
      is still matter of debate. We report the presence of emerin in circulating normal
      human platelets and its absence in platelets from X-linked EMD patients. Since
      platelets are cytoplasmic fragments derived from megakaryocytes, the presence of
      emerin in platelets confirms cytoplasmic localization of this protein, probably
      related to specific functions. We found also that emerin is present in the
      cytoplasm of megakaryocytes, while it is absent in circulating granulocytes.

PMID- 10965800
TI  - Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in
      the myelin protein zero.
AB  - Charcot-Marie-Tooth disease type 1 B (CMT1B) is a demyelinating neuropathy caused
      by mutations in the myelin protein zero (P0) gene (MPZ). A few cases of CMT1B
      were recently found to be characterized by focally folded myelin sheaths in nerve
      biopsy specimens; the significance of this association is unknown. Here, we
      describe two unrelated pedigrees harboring a heterozygous Ser49Leu substitution
      in P0ex. In both pedigrees, the mutation caused a late-onset, relatively mild
      CMT1B; in one pedigree, two patients had atrophy of peroneal muscles but
      hypertrophy of the gastrocnemius muscles. The sural nerve biopsy performed in the
      two index cases revealed an identical chronic demyelinating and remyelinating
      neuropathy dominated by focal foldings of the myelin sheath shaped either as
      tomacula or as out/infoldings. The report adds Ser49Leu to the mutations of P0ex
      associated with focally folded myelin and provides strong evidence that such a
      structural alteration of the myelin sheath reflects a distinct pathogenetic
      mechanism in a subgroup of CMT1B.

PMID- 10965801
TI  - Abnormally phosphorylated protein tau in the cortex of aged individuals of
      various mammalian orders.
AB  - Aged individuals of mammalian species displaying hyperphosphorylated tau protein
      may be suitable natural models for investigating neurodegenerative alterations
      occurring, for example, in Alzheimer's disease. Therefore, autoptic tissue from
      the entorhinal, motor and prefrontal cortices of 14 mammalian species was
      screened using the monoclonal antibody AT8, which is directed against a
      phosphorylated epitope of human tau and applicable to the tissues of aged
      domestic animals, as shown in previous studies. AT8-immunoreactive neuronal
      processes and perikarya were revealed in Campbell's guenon, rhesus monkey,
      baboon, rabbit, spectacled bear, guanaco, reindeer and bison. Signs for
      considerable neuropathological alterations in aged bisons also included neuropil
      threads, whereas AT8 immunoreactivity in the other species was only sparsely
      scattered. Hyperphosphorylated tau in the brain of an 28-year-old rhesus monkey
      was also detected by AT100, PHF-1 and TG-3 antibodies, but only in the
      hippocampal formation and entorhinal cortex, which are known as starting point
      for tangle spreading in the cortex of Alzheimer patients.

PMID- 10965802
TI  - Dynamics of microglial activation after human traumatic brain injury are revealed
      by delayed expression of macrophage-related proteins MRP8 and MRP14.
AB  - Human traumatic brain injury (TBI) is ideally suited for investigation of the
      kinetics of human microglial cell activation as the onset of lesion formation is
      precisely defined. The present study provides evidence of a distinct delay in
      macrophage/microglia response following TBI. Eighteen brains of patients who had
      survived TBI for 1 h to 6 months were analysed by immunohistology. Samples of
      contusional and non-contusional areas were studied using antibodies directed
      against antigens of microglia/ macrophages [major histocompatibility complex
      class II, CD4, interleukin (IL)-16, macrophage-related protein (MRP) 8 and
      MRP14]. IL-16, a natural ligand to CD4, was expressed constitutively by numerous
      microglial cells in all cases throughout the brain. CD4 could be detected
      regularly on perivascular cells. MRP8 and MRP14, which are only expressed on
      activated macrophages and microglial cells, could be detected only within brains
      with a survival time of more than 72 h post TBI. In addition, proliferation of
      microglia detected by MIB-1 was not present until 72 h. This delayed expression
      of the activation markers MRP8 and MRP14 and the proliferation marker MIB-1 is
      comparable to experimental closed head injuries but strictly different from acute
      activation found in ischemic brains.

PMID- 10965803
TI  - Claudin-1 and claudin-5 expression and tight junction morphology are altered in
      blood vessels of human glioblastoma multiforme.
AB  - The aim of the study was to characterize the interendothelial junctions in tumor
      microvessels of five cases of human glioblastoma multiforme. In addition to
      morphological analysis, tumors were screened for the expression of junctional
      proteins, such as occludin, claudin-1, ZO-1 and catenins. The expression of the
      tight junction protein claudin-1 was lost in the majority of tumor microvessels,
      whereas claudin-5 and occludin were significantly down-regulated only in
      hyperplastic vessels. As shown by freeze-fracture analysis, under the conditions
      of tumor growth tight junction particles of endothelial cells were almost
      exclusively associated with the exocytoplasmic fracture face, providing evidence
      for a switch of the particles from the protoplasmic to the external leaflet of
      the endothelial membrane. These results suggest a relationship between claudin-1
      suppression and the alteration of tight junction morphology, which is likely to
      correlate with the increase of endothelial permeability. Underlining the
      undifferentiated state of tumor microvessels, plakoglobin, a crucial protein for
      mature endothelial junctions, was not detectable in most microvessels, whereas
      beta-catenin was abundantly labeled. In this context, it is of particular
      interest that the majority of microvascular pericytes were negative for alpha
      smooth muscle actin, which is a marker of differentiated pericytes, although
      pericytes were frequently found in electron micrographs. In conclusion, the data
      suggest that the increase in microvascular permeability in human gliomas,
      contributing to the clinically severe symptoms of brain edema, is a result of a
      dysregulation of junctional proteins.

PMID- 10965804
TI  - Progressive multifocal leukoencephalopathy and oligodendroglioma in a monkey co
      infected by simian immunodeficiency virus and simian virus 40.
AB  - A rhesus monkey experimentally inoculated with simian immunodeficiency virus
      (SIV) mac251 was killed 42 months later because of poor general condition. CD4
      lymphocyte count which was 3,430/mm3 before inoculation, had decreased to 638/mm3
      2 months before death. Neuropathological examination revealed changes
      characteristic of progressive multifocal leukoencephalopathy (PML) in the white
      matter of the cerebral hemispheres and brain stem. In situ hybridization was
      negative for JC virus but markedly positive for simian virus 40 (SV40) in the
      nuclei of many oligodendrocytes. Many oligodendrocytes also expressed p53. Within
      an area involved by PML, there was a densely cellular tumor with honeycomb
      appearance and elongated vessels characteristic of oligodendrogliomas. Within the
      tumor in situ hybridization for SV40 and immunocytochemistry for p53 were
      negative. Opportunistic infection by SV40 has been occasionally reported in
      experimentally SIV-infected monkeys resulting in PML or malignant astrocytoma.
      Association of JC virus-induced PML and astrocytomas has been reported in three
      human cases without AIDS. In those cases, as in our monkey, polyomaviruses (SV40
      or JC virus) were expressed in the areas with PML but not in the glial tumor.
      Association of PML and oligodendroglioma has not been reported previously to our
      knowledge. The relationship between oligodendrocyte proliferation and
      polyomavirus infection of oligodendrocytes is unclear. Our findings suggest that
      binding of the viral protein to p53 may result in inactivation of the pro
      apoptotic protein favoring the proliferation of a randomly occurring tumoral
      clone of oligodendrocytes.

PMID- 10965805
TI  - Human herpesvirus 6-meningoencephalitis in an HIV patient with progressive
      multifocal leukoencephalopathy.
AB  - Human herpesvirus 6 (HHV6) has been reported as a rare cause of
      meningoencephalitis and leukoencephalitis. We present an HIV-infected patient
      with lesions of progressive multifocal leukoencephalopathy (PML), but also
      meningoencephalitis apparently due to HHV6. Immunohistochemistry for HHV6
      antigens and in situ polymerase chain reaction for HHV6 genome showed many
      positive lymphocytes and microglia in the meningeal and cortical lesions. More
      importantly, dead and dying neurons were conspicuous; some were undergoing
      neuronophagia and some displayed evidence of HHV6 infection. A pathogenic role
      for this almost universal, and usually commensal, virus in inflammatory brain
      lesions and PML is briefly discussed.

PMID- 10965806
TI  - Clinicopathological study of atypical motor neuron disease with vertical gaze
      palsy and ballism.
AB  - The case of a 38-year-old patient with rapidly progressing motor neuron disease,
      complicated by major dysfunction of the extrapyramidal system and of vertical
      gaze is described. Neuropathological examination revealed a degenerative process
      that severely affected the lower motor neurons, as well as the neurons of the
      pars compacta of the substantia nigra, the nucleus of Darkschewitsch, the nucleus
      interstitialis of Cajal, the colliculi superiores, and the pallidum. The long
      tracts were unaffected at all levels of the brain stem and spinal cord. There was
      no convincing evidence for the presence of a multiple system atrophy or
      progressive supranuclear palsy; the results rather revealed a pattern of
      vulnerability characteristic of a variant of motor neuron disease.

PMID- 10965807
TI  - Esophageal reconstruction surgery in oncologic patients: determination of gastric
      emptying time.
AB  - All parts of the gastrointestinal tract are accessible for study using nuclear
      medicine techniques. We have studied the effect of esophageal reconstruction
      surgery, in different periods of time, after surgical procedure. Oncologic
      patients (19) were evaluated after esophageal reconstruction surgery with gastric
      (group II - 14 patients) or colonic tube (group III - 5 patients) and they were
      compared with 15 healthy volunteers (group I). Gastric emptying was performed in
      the same subjects using solid food (egg sandwich) labeled with 99mTc-phytate. In
      emptying gastric studies, the mean (T1/2) of the patients was much faster than
      those of the control (p<0.05) when 1/3 distal tube was considered as stomach.
      However, there was no difference between the T1/2 of group II and group III. We
      concluded that this nuclear medicine method could be useful in the monitoring the
      surgical reconstruction of the esophagus.

PMID- 10965808
TI  - Lymphatic mapping and sentinel lymphadenectomy in early stage breast carcinoma.
AB  - The rate of axillary lymph node metastases is low in early stage breast carcinoma
      and axillary lymph node dissection is controversial in the treatment of these
      patients. Intraoperative lymphatic mapping technique is suggested for the
      identification of metastatic lymph nodes. Intraoperative lymphatic mapping was
      performed on 60 clinical stage I and II patients who were treated at Ankara
      Oncology Hospital between 1996-1998. Patent blue dye was injected in all cases,
      as the tumor was totally excised before mastectomy, into the surrounding breast
      tissue at four different quadrants. Presence of metastases were examined on
      stained lymph nodes (sentinel lymph node: SLN) by frozen-section. Modified
      radical mastectomy was performed including level I, II, III lymph node
      dissection. Metastases were evaluated on the remnants of frozen-section tissues
      and unstained lymph nodes (nonsentinel lymph node: nSLN) in axilla on
      hematoxyline-eosin stained slides and by immunohistochemistry. Forty-nine (81.6%)
      SLNs were identified among 60 cases. In 18 (36.7%) of these 49 patients,
      metastases were detected in SLNs by frozen section. In one case micrometastasis
      was detected in the remnants of frozen-section by immunohistochemistry though it
      was negative with hematoxyline-eosin. There were no metastases in nSLNs of 27
      cases whose SLNs's frozen-sections were tumor free. In 3 cases SLNs were negative
      but metastases were detected in nSLNs (false negative: 6.1%). There were no local
      or systemic complications due to injections of dye. Selective lymph node
      dissections can be performed on early stage breast cancer patients by means of
      lymphatic mapping. This minimally invasive technique identifies metastatic
      axillary lymph nodes with a high degree of accuracy, so we can suggest that, non
      metastatic patients can be treated without axillary dissection.

PMID- 10965809
TI  - Endoscopic follow-up in resected colorectal cancer patients.
AB  - Patients resected for colorectal cancer are at risk for anastomotic recurrence,
      for adenomatous polyps and for metachronous cancer. The present retrospective
      study was conducted to evaluate the incidence of neoplasms of the colon, both
      metachronous or recurrent, in 322 patients. They were observed and resected for
      colorectal cancer between 1970 and 1988, with complete staging, and all agreed to
      be included in a follow-up program (median followup: 105 months). All the
      patients were submitted to colonoscopy once yearly for the first 5 years and then
      every 2 years. Anastomotic recurrence was observed in 22 of the 253 patients who
      underwent resection for rectal or sigmoid adenocarcinoma (8.7%). Sixteen of these
      patients were submitted to a second curative resection with a median survival of
      35 months; the median survival was 6 months in the 6 patients who could not
      undergo this operation (p=0.0018). Metachronous adenomas of the residual colon
      were found in 24 patients and metachronous cancers in 5 at Stage A, according to
      Dukes' classification. In conclusion, a regular colonoscopic surveillance in
      patients resected for colorectal cancer is justified for early detection and
      potential resection of anastomotic recurrences, new primary cancer and
      adenomatous polyps. In patients resected for rectal or sigmoid carcinoma, a
      sigmoidoscopy should be performed every 6 months for the first 2 years for the
      early detection of anastomotic recurrences. In all cases, a colonoscopy should be
      performed every 5 years after surgery to detect metachronous lesions. Before
      surgery, a "clean colon" should always be established to detect possible
      synchronous lesions.

PMID- 10965810
TI  - Primary non-Hodgkin lymphoma of the breast. Is it possible to avoid mastectomy?
AB  - Primary lymphoma of the breast is a rare disease that has been estimated to
      represent from 0.05% to 0.53% of all malignant breast tumors and approximately
      2.2% of all extranodal lymphomas. The aim of this study is to review all cases of
      primary lymphoma of the breast at the Institute of Oncology and Radiology of
      Serbia from 1984 to 1996 in order to determine the incidence, patterns of
      clinical presentation, radiological features, histopathology, mode of therapy and
      outcome of the disease. The criteria for inclusion in this retrospective study
      corresponded to a revision of the original criteria suggested by Wiseman and
      Liao. The clinical histories of ten patients with breast lymphomas were reviewed.
      Clinical follow-up was obtained through a review of the patients hospital chart
      or by direct contact with the patients. Ten cases of primary lymphoma of the
      breast have been identified during the 12-yr period, presenting 0.05% of all
      patients with malignant breast disease. All patients were female, median age at
      diagnosis 58 years (range 49-69), all presented with breast lumps (3 right, 7
      left) of median size 5 cm (range 3.5-8 cm). Mammography and breast echography
      were unable to bring a suspicion of lymphoma. Histologically, 6 cases were
      diffuse large cell, 3 of which with features consistent with immunoblastic
      lymphoma; 2 were diffuse mixed cells and 2 had small lymphocytic morphology. In 4
      out of 5 patients, in the clinical stage corresponding to the "operable breast
      cancer" category, the ex tempore histological analysis could not differentiate
      lymphoma from cancer, so that all of them had mastectomy with axillary
      dissection. Those corresponding to the "locally advanced breast cancer" category,
      escaped mastectomy and a classical biopsy was performed, anticipating eventual
      neoadjuvant procedures. Thus, four patients underwent radical mastectomy, 1 wide
      local excision and 5 diagnostic biopsies. Further treatment included chemotherapy
      for 8 patients. The projected probability of a 10-years survival was 0,60. The
      rarity of this disease, and uneven treatment modalities make prognosis of breast
      lymphoma difficult. It seems that cooperation between the surgeon and the
      pathologist is necessary in order to reach the correct diagnosis during ex
      tempore analysis. With the limitations of available diagnostic procedures, it
      appears that most patients with breast lymphoma, in the stage corresponding to
      the "operable breast cancer" category, will unnecessarily undergo mastectomy and
      axillary dissection as primary treatment approach.

PMID- 10965811
TI  - Quantitative and functional study of breast cancer axillary lymph nodes and those
      draining other human malignant tumors.
AB  - Lymphocyte functional activity from lymph nodes draining human malignancies
      reflects the host immune response against tumour. Breast cancer is the neoplasia
      with the greatest amount of identified antigens but a weak inducer of a host
      efficient immune response. In our study we compared the mitogen stimulated
      proliferative response of cells isolated from metastases-free lymph nodes
      draining breast cancer (Group 1), other malignant tumours (Group 2), and those
      obtained from patients without malignancies (Control group). A significant
      decrease of the proliferative response in cells isolated from lymph nodes
      draining breast cancer was observed comparing it to the other groups.
      Quantitative analysis of B and T cells showed a higher number of B cells than T
      cells in Groups 1 and 2. Moreover, Group 1 presented a two fold increase of T
      cells compared with Group 2. Our results suggest that the immunosuppression
      observed in lymph nodes draining breast cancer is higher than the
      inmunosuppression presented in other malignant tumours and that impaired function
      is not correlated with the increased number of T cells.

PMID- 10965812
TI  - A general survey of glutamine level in different tissues of murine solid tumor
      bearing mice before and after therapy with purified glutaminase.
AB  - Distribution of glutamine level in different tissues of tumor bearing mice such
      as brain, liver, kidney, spleen, large and small intestine and the tumor itself
      were studied in three solid tumor models, viz, Ehrlich ascites carcinoma, Sarcoma
      180 and methylcholanthrene induced carcinoma. Tumor bearing mice were subjected
      to therapy for 7 days with the glutaminase purified from malignant S-180 cell.
      The results exhibit a significant decrease in tumor burden after enzyme therapy.
      Host tissue glutamine levels were significantly elevated in tumor bearing
      untreated mice in comparison to the normal ones, while significant lower values
      were obtained after enzyme therapy. It therefore appears that elevated levels of
      glutamine in host tissue are associated with the tumor burden.

PMID- 10965813
TI  - Effect of Withania somnifera on 20-methylcholanthrene induced fibrosarcoma.
AB  - Administration of an extract from the root of the plant Withania somnifera
      (20mg/dose/animal i.p) was found to inhibit the 20-methylcholanthrene induced
      sarcoma development in mice and increase the life span of tumour bearing animals.
      Administration of Withania could inhibit the lipid peroxide formation (152
      nanomoles/mg protein) (P<0.01) compared with control (198 nanomoles/mg protein).
      Withania could increase the GSH level (7.7 micromoles/mg protein) which was
      lowered in control tumour bearing animals (3.96 micromoles/mg protein). GST level
      was also significantly increased (451 micromoles/min/mg protein) (P<0.001) in
      Withania treated animals compared to control animals (205 micromoles/min/mg
      protein). All the animals in the control group developed sarcoma by the 80th day
      of carcinogen administration. Only 3 animals in the Withania treated group
      developed sarcoma by the 105th day. In control animals the survival rate was 40%
      but in the Withania treated group the survival rate was 100% after 15 weeks of
      carcinogen treatment. These results indicate that Withania could inhibit 20
      methylcholanthrene induced sarcoma development in mice.

PMID- 10965815
TI  - Potential diagnostic, prognostic and therapeutic implications of some new
      regulatory proteins in hematologic malignancies.
AB  - Multiple cell surface receptors play an important role in the biology of
      hematological malignant cells. Like already clustered monoclonal antibodies, the
      use of new markers of differentiation provide some new information about their
      structure and function. Here we consider the role of few selected regulatory
      proteins that are most frequently involved in the processes of activation, cell
      differentiation and proliferation of human hematological malignant cells. These
      molecules, being either lineage-restricted or multi-lineage cell activation ones,
      are involved in cell-cell and cell-matrix communications. They are involved in
      various leukocyte functions such as mobility, interaction with endothelium, and
      homing. Since physiologic cell growth involves not only cell division, but also
      programmed-cell death, we considered some apoptosis-regulatory molecules
      implicated in the clinical heterogeneity of hematological malignancies. The
      presence or absence of staining for these molecules is not only an important
      discriminatory immunophenotypic feature, but it appears useful also for prognosis
      and particularly in an experimental therapeutical setting. The prognostic
      significance of cell-expression of these molecules has not yet been clearly
      established, but it might be helpful in the evaluation of stability and
      progression of the disease.

PMID- 10965814
TI  - Bleomycin-induced chromosome damage in lymphocytes indicates inefficient DNA
      repair capacity in breast cancer families.
AB  - In vitro mutagen susceptibility has been observed as a predictor of cancer risk.
      To evaluate susceptibility to mutagen, we have studied the response to in vitro
      bleomycin (BLM) treatment in cultured peripheral blood lymphocytes (PBL) of 9
      breast cancer families (BCFs). Eleven breast cancer patients (BCPs) and 36
      healthy blood relatives (HBRs) from BCFs were included in the study. Data were
      compared with 22 healthy control women. The frequencies of chromosomal
      aberrations were evaluated after exposure to BLM in the last five hours. Mean
      frequency of BLM-induced chromosomal aberrations per cell (CA) observed among
      BCPs was significantly higher as compared to their HBRs as well as control
      subjects. Moreover, mean BLM-induced CA/cell value observed for HBRs was also
      significantly higher than that of control subjects. In comparison to controls, it
      was observed that there was four times more cancer risk in BCPs (OR=4.148, 95%
      CI=5.83-687.46) and 2.5 times more cancer risk in HBRs (OR=2.67, 95% CI=5.31
      39.25). Lymphocytes from 90% of BCPs and 69% of HBRs were found to be sensitive
      to BLM (using a cutoff value = controls group mean + 1 SD). Thus, lymphocytes of
      BCPs and their HBRs were more sensitive to BLM exposure as compared to controls.
      Our finding indicated inefficient DNA repair capacity in BCFs. The HBRs in BCFs,
      having increased BLM-sensitivity, may be at higher risk to develop a similar
      cancer.

PMID- 10965817
TI  - Expression of thymidylate synthase in relation to survival and chemosensitivity
      in gastric cancer patients.
AB  - Expression of thymidylate synthase (TS) has been studied as a prognostic factor
      and mechanism of drug resistance in gastric cancers. The relationship between TS
      expression in surgically resected specimens and clinicopathological factors was
      examined in 216 gastric cancer patients. Immunohistochemical demonstration of the
      protein was achieved using an anti-TS polyclonal antibody. Positive TS staining
      was observed in 50 patients (23.1%). Lymph node metastasis was more frequent in
      patients with TS-positive tumors than in those with TS-negative tumors (P<0.01).
      Patients were followed for more than 5 years and survival was examined. In 163
      patients who received fluorouracil (FU)-based chemotherapy, the overall 5-year
      survival rate was 41.8% for patients with TS-positive tumors and 57.0% for
      patients with TS-negative tumors (P<0.01). In the 53 patients who did not receive
      chemotherapy, these figures were 25.6% and 79.5%, respectively (P<0.05). In
      patients with T3 gastric cancer who were treated with curative gastrectomy,
      however, FU-based chemotherapy did not affect survival of either patients with TS
      positive tumors or with TS-negative tumors. Multivariate analysis also revealed
      TS expression to be a significant variable for predicting postoperative survival
      (P<0.05). These results indicate that TS expression can be used as an independent
      prognostic factor for patients with gastric cancer. However, TS expression is not
      a major predictor of the efficacy of FU-based chemotherapy.

PMID- 10965816
TI  - The targeted expression of interleukin-2 in human hepatocellular carcinoma cells.
AB  - To improve the safety and efficiency of human hepatocellular carcinoma (HCC) gene
      therapy, we explored the use of a liver-specific promoter and a tumor-specific
      enhancer to achieve regular IL-2 gene expression for treatment of HCC. The human
      alpha-fetoprotein (AFP) enhancer [E(AFP)] and the albumin promoter [P(ALB)] were
      amplified from human genomic DNA. We used eukaryotic expression vector pcDNA-3
      for the delivery of the IL-2 gene because this plasmid is a non-transient, fast
      selection expression vector. A recombinant plasmid was constructed including the
      selectable marker neoR gene and the human IL-2 gene derived by the E(AFP) -
      P(ALB). The liver-predominant expression pattern of the IL-2 gene was observed in
      the medium of the transfected cells. When human HCC cell lines displaying
      different levels of AFP and non-hepatocyte tumor cell lines were transfected with
      the recombinant plasmid, IL-2 was expressed highly in AFP and albumin-positive
      HCC cells, but low in nonhepatocyte tumor cells. Moreover, the expression level
      of IL-2 gene was positively proportional to the level of AFP expression in the
      transfected cells.

PMID- 10965818
TI  - L-MYC and GSTM1 polymorphisms are associated with unfavourable clinical
      parameters of gliomas.
AB  - L-MYC and GSTM1 genotypes were analysed in glioma patients (GP) and healthy
      donors (HD). None of these genes appeared to influence the risk of this disease,
      however both polymorphisms correlated with unfavourable clinical parameters of
      gliomas. In particular, S allele of the L-MYC was overrepresented in the relapsed
      patients (P < 0.05), and GSTM1-null genotype was associated with the advanced
      tumour grade (P < 0.05). Patients, but not donors, demonstrated frequent
      combination of SS L-MYC homozygosity with GSTM1(-) variant (P < 0.01 ), as well
      as a correlation between LL L-MYC homozygosity and GSTM1 (+) genotype (P < 0.05).

PMID- 10965819
TI  - The nuclear morphometry by image analysis in the histopathologic diagnosis of
      lung cancer.
AB  - Classification of small cell lung cancer and non small cell lung cancer can
      sometimes be difficult to establish by light microscopy. Our aim was to determine
      the value of computerised interactive nuclear morphometry in the diagnosis of
      small cell lung cancer of intermediate type and non small cell lung cancer in
      thirty-nine histologic specimens. Histologic sections were measured by Sigma Scan
      software package with regard to nuclear big axis, small axis, perimeter, area and
      shape factor. Statistical analysis showed that nuclear minor axis values, at
      least, showed pronounced differences between small cell lung carcinomas of the
      intermediate type and non small cell lung carcinomas. So, the latter nuclear
      parameter may be used as a complementary tool in the histopathologic differential
      diagnosis of lung cancer.

PMID- 10965820
TI  - Grafting of stomach tissue into the duodenum in F344 rats results in chimeric
      crypts and tumor development.
AB  - Gastric tissue was transplanted from the fundic and pyloric mucosa of 8-week old
      female F344 rats into the duodenum of males. Autopsy, 12 months after the
      operation, revealed grafts associated with persistent stones in the duodenum
      and/or calcification in the tissue. Pepsinogen positive chimeric glands with
      goblet cells also appeared in the grafts which gave rise to tumors in 18 out of
      45 animals (40%). In conclusion, stomach grafts re-differentiate into intestine
      with goblet cells in the duodenum and this process predisposes to tumor
      development.

PMID- 10965821
TI  - Experimental study of lymphogenous peritoneal cancer dissemination: migration of
      fluorescent-labelled tumor cells in a rat model of mesenteric lymph vessel
      obstruction.
AB  - Primary gastrointestinal cancer frequently spreads to the mesentery, omentum and
      other parts of the peritoneum, and these deposits are generally considered to be
      induced by intraperitoneal seeding from the primary lesion. However, a few
      peritoneal metastatic cases or cases with positive intraperitoneal lavage
      cytology, without serosal infiltration, have been reported. Most of peritoneal
      dissemination is certainly attended with serosal involvement of gastrointestinal
      malignancy. Nevertheless, we observe an unusual case of peritoneal dissemination
      without definite serosal invasion of the malignancy. And peritoneal dissemination
      is likely to be concomitant with lymph node metastasis in both cases with and
      without definite serosal invasion. In this study, we examined peritoneal cancer
      dissemination from the viewpoint of lymphogenous metastasis. For the model of
      lymphatic invasion, we established an animal experimental model of mesenteric
      lymph vessel obstruction. With these models, lymphangiographical studies were
      made on the fourth postoperative day (ten animals each) and we obtained
      mesenteric lymphangiograms of extensive mesenteric lymph vessels and reflux of
      lymph distal to the obstruction point from all ten animals. Next, in these
      experimental models, fluorescent-labelled tumor cells (rat hepatoma cell line, N1
      S1) were infused from the mesenteric lymph node distal to the obstruction point
      on the fourth postoperative day (five animals each), and the migration of these
      tumor cells was investigated via fluorescent micrography. Subsequently, the
      fluorescent-labelled tumor cells were revealed in the mesenteric lymph nodes,
      mesenteric lymph vessels, interstitial tissues of the mesentery, submucosal lymph
      nodules and mucosal layer of the small intestine. Hence, lymphatic invasion and
      obstruction may cause extensive peritoneal dissemination via the lymphatic route.

PMID- 10965822
TI  - Effect of prostaglandin E1 on vascular endothelial growth factor production by
      human macrophages and colon cancer cells.
AB  - We previously demonstrated that cyclooxygenase-2 (COX-2) was predominantly
      expressed in macrophages of sporadic human colonic adenomas; however, the role of
      COX-2-expressing cells during colon carcinogenesis has not yet been elucidated.
      In the present study, we showed the effect of PGE, on vascular endothelial growth
      factor (VEGF) production by PMA-differentiated U937 cells, a human macrophage
      model (H-Mac), and by human colon cancer cells T84. PGE1 dramatically induced
      VEGF production by H-Mac, but not that by T84. PGE1 significantly increased
      intracellular cAMP formation by H-Mac, but only modestly increased that by T84. 8
      bromo-cAMP and cholera toxin also increased VEGF production by H-Mac. In
      contrast, neither of these agents modulated VEGF production by T84. EP2 and EP4
      (PGE specific receptors) mRNA was expressed in both cells. PG dramatically
      increased VEGF production by activated macrophages, but not by cancer cells,
      through a specific PGE receptor-mediated process. These findings suggest that PGs
      produced by COX-2-expressing macrophages induce VEGF production by macrophages,
      but not by cancer cells, in an autocrine fashion.

PMID- 10965823
TI  - Epidermal growth factor receptor, MUC-1 and MUC-2 in bladder cancer.
AB  - The aim of this study was to investigate the immunohistochemical expression of
      epidermal growth factor receptor (EGFR), mucin-1 (MUC-1) and mucin-2 (MUC-2)
      proteins in primary bladder carcinomas and to compare EGFR and MUC staining
      patterns with the histological findings, grade and stage of bladder carcinoma.
      Fifty-six surgical specimens obtained from superficial and deeply invasive
      bladder carcinomas were studied. Of the 56 bladder tumors 42 (75%) expressed
      EGFR, 34 (60.71%) MUC-1 and 15 (26.78%) MUC-2; while 7 tumors (12.5%) coexpressed
      MUC-1 and MUC-2 proteins. Immunohistochemical scores showed higher levels of EGFR
      than of MUC-1 (P <0.05) and MUC-2 (P = 0.000) and higher levels of MUC-1 than MUC
      2 (P = 0.0010). EGFR and MUC-1 expression was stronger in high-grade tumors
      (grade 2/3) than in low-grade (grade 1/2) ones (P <0.05) and stronger in muscle
      invasive tumors (T2-T4) than in superficial (Ta-T1) ones. Linear regression
      showed a significant (P <0.05) correlation between EGFR and MUC-1 proteins, but
      no correlation between EGFR and MUC-2 or between MUC-1 and MUC-2.
      Immunohistochemical expression of EGFR, MUC-1 and MUC-2 increases as primary
      bladder carcinomas acquire a more aggressive phenotype. Differences in the
      distribution of EGFR and mucins within the urothelium may be of diagnostic and
      prognostic value. These antigens may be useful as markers for bladder malignancy.

PMID- 10965824
TI  - Augmentation of UDP-GalNAc: Fucalpha1-2Gal alpha1-3 N-acetylgalactosaminyl
      transferase activity in nitrosamine-induced hamster pancreatic cancers.
AB  - Pancreatic cancers induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters
      produce blood group-A antigen (BG-A Ag), which is not present in the normal
      pancreas. To understand the neo-expression mechanism of BG-A Ag, we examined
      uridine diphosphate (UDP)-N-acetylgalactosamine (GalNAc): fucose (Fuc) alpha1-2
      galactose (Gal) alpha1-3 GalNAc transferase (alpha1-3 GalNAc Tf) activity, the
      enzyme responsible for BG-A production. The specific activity of alpha1-3 GalNAc
      Tf in pancreatic cancers was approximately 8,000 nmole/g protein/h, whereas it
      was absent from the normal pancreas. Although the antrum and colon express A-Tf
      and BG-A Ag, the divalent cation requirements of alpha1-3 GalNAc Tf in these
      tissues were different from those of cancers. These results suggest that alpha1-3
      GalNAc Tf is activated during BOP-induced pancreatic carcinogenesis, and that
      there are multiple alpha1-3 GalNAc Tf isozymes present in hamster tissues.

PMID- 10965825
TI  - Pancreatic duct cell carcinoma with positive 111In Octreotide uptake.
AB  - Duct cell adenocarcinomas may produce neuroendocrine markers such as pancreatic
      polypeptide, gastrin and gastrin releasing hormones. A 53 year old patient, with
      a history of insulin dependent diabetes, was found to have a pancreatic mass
      which was later pathologically demonstrated to be a duct cell adenocarcinoma. The
      tumor produced elevated circulating neuroendocrine markers specifically gastrin
      and pancreatic polypeptides. An 111In Octreotide imaging showed definite uptake
      of Octreotide by the tumor. The patient was subsequently treated with
      Somatostatin analog which resulted in the reduction of some of the circulating
      endocrine markers. The patient had essentially six months of asymptomatic
      clinical remission but then she relapsed. Octreotide scanning could be useful for
      selected patients with pathologic diagnosis of duct cell adenocarcinoma, because
      some tumors may have neuroendocrine features and can be imaged, and might even
      respond to Somatostatin analog therapy.

PMID- 10965826
TI  - Benign tumors of heterotopic tissue in the thyroid gland: a report of two cases
      of lipomatous lesions.
AB  - A report of two cases, concerning heterotopic nests of fat cells in the thyroid
      gland, is presented here together with a review of lipomatous lesions in the
      literature. Both cases involved patients who presented with goiter; one had
      Grave's disease and the other had adenomatous hyperplasia. The fat cells were
      principally located in the subcapsular areas and scattered among the follicles.
      The distribution of the immunohistochemical staining, and the morphologic
      characteristics of the adipose tissue, suggested a probable origin of the fat
      cells from inclusion nests during embryogenesis of the thyroid gland.

PMID- 10965827
TI  - Primary low grade B-cell lymphoma of the dura in an immunocompetent patient.
AB  - Primary central nervous system lymphomas (PCNSL) represent only 1% of all non
      Hodgkin's lymphomas (NHLs). A 66 year-old woman was hospitalized due to multiple
      episodes of syncope and seizures which occurred the week before admission to the
      hospital. A computerized tomography (CT) scan of the brain showed a right
      parietal lesion suggesting a subdural effusion. The patient was operated and a
      dural lesion extending to the epidural space and cerebral cortex was excised.
      Histologic findings suggested diagnosis of a low-grade lymphoma of the mucosa
      associated lymphoid tissue (MALT) type. The patient was treated with radiation
      therapy and has now completely recovered 12 months after surgery.

PMID- 10965828
TI  - Quality of life and severity of symptoms in gastro-oesophageal reflux disease: a
      clinical review.
AB  - My purpose is to review the quality of life (QoL) instruments used in the
      assessment of gastro-oesophageal reflux disease (GORD) and assess the effects of
      GORD on quality of life. Many instruments have been used in the assessment of
      quality of life in patients with GORD, and these have varied both in quality and
      purpose. In general, the choice of instrument depends on its purpose. Several
      investigators, using generic quality of life instruments, have shown that GORD
      significantly reduces QoL, and its effects are comparable with those of
      congestive heart failure. However, these generic instruments do not seem to be
      sensitive enough to measure the effects of treatments on GORD. For this, disease
      specific instruments are more appropriate. Both medical and surgical treatment
      has been shown to improve QoL. The choice of instrument is entirely dependent on
      the investigator's reason for measuring QoL in GORD patients.

PMID- 10965829
TI  - Management of minor head injuries in emergency departments in Sweden. Time for a
      new strategy?
AB  - OBJECTIVE: To study how patients with minor head injuries are currently managed.
      DESIGN: Questionnaire to senior residents in emergency departments and data from
      registers covering all in-hospital care in Sweden. SETTING: All 92 emergency
      departments in Sweden. RESULTS: The response rate to the questionnaire was 100%.
      In Sweden, 75 emergency departments treat patients with minor head injuries. Four
      departments are paediatric. General surgeons are the main providers (87%) of care
      for patients with minor head injuries. All hospitals admit patients with a
      history of unconsciousness or amnesia. Skull radiography is not used routinely.
      The estimated use of computed tomography (CT) varies between 2% and 80%, the mean
      being 22%. The need for CT, or the result thereof, is not the deciding factor for
      admission. In 1996, 16877 patients were treated as inpatients for minor head
      injuries, (191/100000 inhabitants). The admission rates varied widely among
      departments, and the total figures have been constant since 1987. The mean
      hospital stay was 1.6 days, so a large number of hospital days are consumed. The
      resources more than cover routine CT investigations for those seeking care, and
      hospital care for those with abnormal findings or special needs. CONCLUSION: In
      Sweden, patients with minor head injuries are routinely admitted to hospital for
      observation. The estimated use of CT varies considerably. No clinics report using
      CT to triage patients for admission, a strategy that would be consistent with
      effectiveness and economic arguments.

PMID- 10965830
TI  - Tissue gas tensions in patients with necrotising fasciitis and healthy controls
      during treatment with hyperbaric oxygen: a clinical study.
AB  - OBJECTIVE: To investigate the effect of hyperbaric oxygen (HBO) treatment on
      tissue oxygen and carbon dioxide tensions in patients with necrotising fasciitis
      and healthy volunteers. DESIGN: Clinical study in patients and healthy controls.
      SETTING: University hospital, Finland. SUBJECTS: 6 patients with necrotising
      fasciitis and 3 healthy volunteers. INTERVENTIONS: Subcutaneous tissue PO2 and
      PCO2 tensions were measured directly in patients with necrotising fasciitis and
      in healthy volunteers during normobaric and hyperbaric conditions. Arterial blood
      PO2 and PCO2 tensions were measured only in the patients. Tissue gas tensions
      were measured with a Silastic tube tonometer implanted in the brachial
      subcutaneous tissue of both patients and controls as well as in the subcutaneous
      tissue of the patients in the immediate vicinity of the necrotising process. The
      diagnosis of necrotising fasciitis was made on the basis of the presence of
      typical clinical signs and symptoms, intraoperative findings, and microbiological
      observations. MAIN OUTCOME MEASURES: Arterial and subcutaneous tissue PO2 and
      PCO2 tensions. RESULTS: In patients with necrotising fasciitis the arterial PO2
      rose about 7-fold whereas the arterial PCO2 increased only slightly during
      exposure to 2.5 absolute atmospheres (ATA) of oxygen. During HBO the subcutaneous
      tissue PO2 increased four to five fold from the baseline and CO2 tensions also
      increased, but to a lesser degree, in both healthy and infected tissues. In
      patients with necrotising fasciitis, the PO2 was higher, but not significantly
      so, in the vicinity of the infected area than in the healthy tissue. CONCLUSION:
      Under hyperbaric conditions the subcutaneous PO2 in patients with necrotising
      fasciitis rose higher in the vicinity of the infected area than in the healthy
      tissue, which may be the result of vasodilatation and increased microcirculation
      induced by the inflammatory process associated with infection or it may be the
      result of decreased local tissue oxygen utilisation, or both. The tissue PCO2
      values tended to rise during HBO probably from hypoventilation or reduced CO2
      washout from tissue because venous blood haemoglobin was fully saturated with
      oxygen.

PMID- 10965831
TI  - Operations for extrahepatic bile duct cancers: are the results really improving?
AB  - OBJECTIVE: To find out if our results for the treatment of extrahepatic bile duct
      cancer have improved we reviewed our latest patients as a comparison to a
      previously reported series from this department. DESIGN: Retrospective study.
      SETTING: Tertiary referral centre, Sweden. SUBJECTS: 102 patients who presented
      with extrahepatic bile duct cancer 1979-1995. MAIN OUTCOME MEASURES: Morbidity,
      mortality, and short and long term survival. RESULTS: 16 patients had various
      types of resection, which were radical in 14 according to the surgeon and in 10
      according to the pathologist. One patient (6%) died in hospital, and 1 (44%)
      developed complications. 13 patients had other operations that did not involve
      resection, 23 had laparotomy alone, 61 had biliary drainage either by
      percutaneous transhepatic cholangiography (PTC) or endoscopy, and 10 had no
      active treatment. One patient of the 16 (6%) who had resections has survived for
      more than five years and another one is still alive after 40 months. CONCLUSION:
      Long term survival has not improved for patients with extrahepatic bile duct
      cancer in our hospital during the last decades.

PMID- 10965832
TI  - Systemic inflammatory responses during laparoscopic and open inguinal hernia
      repair: a randomised prospective study.
AB  - OBJECTIVE: To see if the inflammatory responses during and after laparoscopic and
      open inguinal hernia repairs differed. DESIGN: Randomised prospective study.
      SETTING: County hospital, Denmark. PATIENTS: 18 men aged 25-77 years with
      unilateral inguinal hernias. INTERVENTIONS: Ten patients had a laparoscopic
      repair and 8 an open tension-free repair. MAIN OUTCOME MEASURES: Serum
      concentrations of interleukin (IL)-2 receptors (R) of the alpha group (IL
      2Ralpha), IL-6, anti-IL-6, IL-10, tumour necrosis factor (TNF)-alpha, sTNF-RI and
      sTNF-RII before and 2, 6, 12, and 24 hours after the repairs. Duration of
      operation and time for return to normal activities or work were also recorded.
      RESULTS: Serum IL-6 concentrations increased significantly after operation in
      both groups (p < 0.0001), but the increase was significantly higher after open
      than after laparoscopic surgery at all sampling times (p = 0.00) at 6 hours
      postoperatively). Anti-IL-6 and IL-10 remained undetectable at all time points.
      There were no significant differences or increases in the concentrations of TNF
      alpha or sTNF-RII. However, sTNF-RI concentrations increased significantly in
      both groups (p < 0.001) though there was no difference in between the two groups.
      IL-2Ralpha decreased significantly in both groups (p < 0.01) with no differences
      between the groups. The median operation time was 85 min (range 55-100 min) in
      the laparoscopic group and 52 min (range 45-79 min) in the "open" group (p <
      0.01). Median time to return to normal activities/work were 2 and 13 days after
      laparoscopic and open operations, respectively (p < 0.01). CONCLUSION: The
      surgical trauma of laparoscopic inguinal hernia repair is less than that of open
      tension-free hernia operations as assessed by circulating mediators of the
      postoperative inflammatory response. The clinical relevance of this finding must
      be evaluated in larger randomised studies.

PMID- 10965834
TI  - Is tumour angiogenesis a prognostic factor in patients with colorectal cancer and
      no involved nodes?
AB  - OBJECTIVE: To examine a possible association between tumour angiogenesis and
      conventional prognostic variables and to assess the prognostic value of the
      variables examined in patients with colorectal cancer, with no involved nodes.
      DESIGN: Retrospective study. SETTING: University hospital, Italy. SUBJECTS: 119
      patients who had had colorectal cancers resected for cure with no involved nodes
      between 1985-1990. INTERVENTIONS: The three microscopic fields with the most
      microvessels were identified by immunohistochemical techniques. 10 high-power
      fields in each area were used for the microvessel count and the mean values
      indicated the microvessel density. MAIN OUTCOME MEASURES: Correlation of
      microvessel density with conventional prognostic factors, recurrence rates, and
      survival. RESULTS: There was a significant correlation between microvessel
      density and sex, women having a higher density than men (p < 0.05), but no
      significant correlations between density and recurrence rates or survival.
      Multivariate analysis did not indicate that microvessel density had a prognostic
      role. CONCLUSION: Microvessel density in colorectal cancer without involved nodes
      does not correlate with conventional prognostic factors and provides no
      prognostic information.

PMID- 10965833
TI  - Prospective double-blind randomised study of a new regimen of pre-emptive
      analgesia for inguinal hernia repair: evaluation of postoperative pain course.
AB  - OBJECTIVE: To evaluate the effectiveness of a new regimen of pre-emptive
      analgesia on the development of postoperative pain after inguinal hernia repair.
      DESIGN: Prospective, double-blind, randomised study. SETTING: University
      Hospital, Germany. SUBJECTS: 70 consecutive patients who had primary unilateral
      inguinal hernia repairs. INTERVENTIONS: A new regimen of pre-emptive analgesia
      with bupivacaine that was infiltrated preoperatively, intraoperatively, and
      postoperatively was tested. The control group were given saline infiltrations at
      the same times. Pain was measured up to postoperative day 30 using the visual
      analogue scale (VAS), the verbal rating scale (VRS), and by recording patient
      controlled use of ibuprofen suppositories. RESULTS: Pain was significantly less
      in the pre-emptive analgesia group than in the control group during the first 10
      days postoperatively as assessed by VAS and VRS (p < 0.05). Analgesic consumption
      was also significantly reduced in the pre-emptive analgesia group (p < 0.05).
      Multivariate analysis showed that bupivacaine infiltration (pre-emptive
      analgesia) was associated with significantly less postoperative pain (p <
      0.0001). CONCLUSION: This regimen of pre-emptive analgesia is an effective and
      safe method of reducing postoperative pain and analgesic consumption after
      inguinal hernia repair.

PMID- 10965835
TI  - Prognostic value of postoperative carcinoembryonic antigen concentration and
      extent of invasion of resection margins after hepatic resection for colorectal
      metastases.
AB  - OBJECTIVE: To evaluate the prognostic value of postoperative concentration of
      carcinoembryonic antigen (CEA) and extent of surgical margins after resection of
      liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING:
      Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases
      after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases
      MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate
      and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86
      months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and
      invaded in 9 patients. On univariate analysis, a postoperative concentration of
      CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width
      of the resection margin was not of prognostic importance. There was no
      correlation between width of resection margins and postoperative concentration of
      CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4
      ng/ml or more were associated with increased risk of death (relative risk 7.3;
      95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA
      offers better prognostic discrimination than the width of resection margins after
      resection of liver metastases from colorectal tumours. Some patients with invaded
      resection margins did survive for 3 years, but no patient did whose CEA
      concentration was 4 ng/ml or more. The definition of a potentially curative
      hepatic resection should include a postoperative CEA concentration of <4 ng/ml
      (within the reference range).

PMID- 10965836
TI  - Prevention of blood-transfusion-induced impairment of anastomotic healing by
      leucocyte depletion in rats.
AB  - OBJECTIVE: To find out what effect whole blood and leucocyte-depleted blood
      transfusions had on the healing process of intestinal anastomoses in rats.
      DESIGN: Experimental study. SETTING: Teaching hospital, Greece. SUBJECTS: 100
      Wistar rats in five groups of 20 each. INTERVENTIONS: Small and large bowel
      anastomoses were made and the five groups were given normal saline, homologous
      whole blood, heterologous whole blood obtained from PVG rats, homologous
      leucocyte-depleted blood or heterologous leucocytedepleted blood during the
      operation. MAIN OUTCOME MEASURES: Bursting pressures of anastomoses on the third
      and seventh postoperative days and infective complications. RESULTS: The groups
      given whole blood transfusions had significantly more anastomotic abscesses than
      controls (p = 0.003 compared with heterologous, p = 0.05 compared with homologous
      for the small bowel, and p = 0.007 for the large bowel). The pressure
      measurements indicated a significant reduction in anastomotic strength in the
      same groups compared with the control group (p = 0.0001/p = 0.001 on the third
      postoperative day, and p = 0.00001/p = 0.0004 on the seventh postoperative day
      for small and large bowel, respectively). There was no reduction in anastomotic
      strength in the leucocyte-depleted blood groups. CONCLUSIONS: Transfusion of
      leucocyte-depleted blood does not seem to impair intestinal anastomotic healing
      and carries an acceptable incidence of postoperative complications.

PMID- 10965837
TI  - Reduction in formation of peritoneal adhesions by methylene blue in rats: a dose
      response study.
AB  - OBJECTIVE: To find out if the ability of methylene blue given intraperitoneally
      to reduce surgically-induced adhesions in rats is concentration dependent.
      DESIGN: Random, controlled prospective study. SETTING: Teaching hospital, Israel.
      ANIMALS: Seventy female Wistar rats. INTERVENTIONS: Intraperitoneal adhesions
      were generated in rats by scraping the anterior wall of the uterine horn. They
      were then given either saline or serially diluted methylene blue
      intraperitoneally. Additional rats received identical treatments, but without the
      serosal damage. OUTCOME MEASURES: Graded formation of adhesions, two weeks later.
      RESULTS: In the rats treated with methylene blue 1%, adhesion formation was
      similar to that in sham operated rats and was significantly lower (p < 0.001)
      than in all other groups. CONCLUSION: Methylene blue 1%, and to lesser degree
      0.5%, had the best anti-adhesion potential. Lower methylene blue concentrations
      were only partially effective, and much high concentrations may cause adverse
      effects.

PMID- 10965838
TI  - Effects of intraperitoneal mitomycin C adsorbed on activated carbon on adhesion
      formation and mesothelial cells in vitro.
AB  - OBJECTIVE: To investigate the incidence of adhesions after intraperitoneal
      instillation of mitomycin C adsorbed on activated carbon (MMC-CH). DESIGN: Animal
      and laboratory studies. SETTING: University hospital, Germany. ANIMALS: 90
      Sprague-Dawley rats. INTERVENTIONS: Laparotomy, small bowel anastomosis, and
      intraperitoneal instillation of saline (controls, n = 27), activated carbon alone
      (n = 24) or MMC-CH (n = 26). Cultures of monolayers of human mesothelial cells.
      MAIN OUTCOME MEASURES: Measurements of adhesions by planimetry. Toxicity of
      mitomycin C alone and charcoal alone in mesothelial cell monolayers as reflected
      by cell proliferation and measurement of lactate dehydrogenase activity.
      Concentrations of plasminogen activator (tPA) and plasminogen activator inhibitor
      1 (PAI-1) as measures of the fibrinolytic activity of mesothelial cells. RESULTS:
      Both activated carbon and MMC-CH caused a significant increase of adhesion
      formation in rats. Activated carbon also reduced the fibrinolytic activity of
      mesothelial cells, and mitomycin C caused concentration-dependent cytotoxicity in
      vitro. CONCLUSIONS: Activated carbon combined with high concentrations of
      mitomycin C may cause intraperitoneal infective complications by increasing the
      rate of adhesion formation and reducing the fibrinolytic activity of mesothelial
      cells. We recommend a new absorbable carrier for intraperitoneal chemotherapy.

PMID- 10965839
TI  - A new technique for tying the surgeon's knot.
AB  - A technique for tying the surgeon's knot is explained. This is based on
      considering that the active hand has two clasps, an inferior one formed by the
      thumb and the ring finger, which fixes the distal end of the ligature, and
      another superior clasp formed by the index and middle finger, whose rotating
      mobility makes it possible to wrap the proximal tips of the ligature around them
      one or more times and then to grasp the distal end and pull it through the
      proximal loops.

PMID- 10965840
TI  - Perforated diverticulitis of the transverse colon.

PMID- 10965841
TI  - Laparoscopic management of upper gastrointestinal bleeding from a splenic artery
      pseudoaneurysm.

PMID- 10965842
TI  - Malignant melanoma of the rectum.

PMID- 10965843
TI  - Insular thyroid carcinoma in adolescents.

PMID- 10965844
TI  - Appendicectomy under local anaesthesia: is it worth considering its routine use?

PMID- 10965845
TI  - Colorectal resection and primary anastomoses in patients aged 70 and older: reply
      to Wexner invited commentary.

PMID- 10965847
TI  - Casein kinase II phosphorylation of the human papillomavirus-18 E7 protein is
      critical for promoting S-phase entry.
AB  - The human papillomavirus type 18 E7 protein subverts the pRb/E2F pathway to
      promote S-phase reentry by postmitotic, differentiated primary human
      keratinocytes in support of viral DNA amplification. We prepared a panel of HPV
      18 E7 mutations in pRb binding or in casein kinase II (CKII) phosphorylation. Our
      results showed that the ability of E7 binding to pRb correlated with the
      activation of DNA polymerase alpha or cyclin E to various extents in
      differentiated keratinocytes of organotypic cultures but was insufficient to
      induce the proliferating cell nuclear antigen. Proteins mutated in the CKII
      recognition sequence or in one or both serine substrates (S32 and S34) bound pRb
      in vitro, but only those with negative charges at these two residues induced
      proliferating cell nuclear antigen effectively. Nevertheless, unscheduled
      cellular DNA synthesis occurred very inefficiently relative to the wild-type E7,
      if at all. Thus, both pRb binding and CKII phosphorylation of E7 are critical for
      activating cellular genes essential for S-phase entry.

PMID- 10965848
TI  - Bcl-2 and Bax are differentially expressed in hyperplastic, premalignant, and
      malignant lesions of mammary carcinogenesis.
AB  - Previously, we found that vorozole (Vz), a nonsteroidal aromatase inhibitor,
      suppresses the development and progression of mammary tumors in rats. Here we
      evaluated for the first time the expression of cell death-related proteins Bcl-2
      and Bax in hyperplastic, premalignant (carcinoma in situ), or malignant
      (carcinoma) lesions of mammary carcinogenesis; we also assessed whether these
      proteins are involved in mediating Vz-induced cell death in tumors. We found that
      Bcl-2 and Bax were equally expressed in epithelial cells of terminal end buds,
      ducts, and alveoli. However, in myoepithelial cells, the level of Bax expression
      was much higher than the level of Bcl-2 expression. Bcl-2 and Bax levels in
      hyperplastic lesions were similar to those of normal mammary epithelial cells but
      lower in most carcinomas in situ and carcinomas. In animals with established
      mammary tumors, Vz induced apoptotic cell death, which was primarily associated
      with a decrease in Bcl-2 and, to a lesser extent, with a decrease in Bax. These
      data support the hypothesis that Bcl-2 loss is more potent than Bax gain in
      regulating apoptotic cell death in mammary tumors.

PMID- 10965846
TI  - RING3 kinase transactivates promoters of cell cycle regulatory genes through E2F.
AB  - RING3 is a novel, nuclear-localized, serine-threonine kinase that has elevated
      activity in human leukemias. RING3 transforms NIH/3T3 cells and is activated by
      mitogenic signals, all of which suggest that it may play a role in cell cycle
      responsive transcription. We tested this hypothesis with transient transfection
      of RING3 into fibroblasts and assayed transactivation of the promoters of cyclin
      D11 cyclin A, cyclin E, and dihydrofolate reductase (dhfr) genes. RING3
      transactivates these promoters in a manner dependent on ras signaling. A kinase
      deficient point mutant of RING3 does not transactivate. Mutational analysis of
      the dhfr promoter reveals that transactivation also depends on the presence of a
      functional E2F binding site. Furthermore, ectopic expression of Rb protein, a
      negative regulator of E2F activity, suppresses the RING3-dependent
      transactivation of this promoter. Consistent with a potential role of E2F in
      RING3-dependent transcription, anti-RING3 immunoaffinity chromatography or
      recombinant RING3 protein affinity chromatography of nuclear extracts copurified
      a protein complex that contains E2F-1 and E2F-2. These data suggest that RING3 is
      a potentially important regulator of E2F-dependent cell cycle genes.

PMID- 10965849
TI  - 8S-lipoxygenase products activate peroxisome proliferator-activated receptor
      alpha and induce differentiation in murine keratinocytes.
AB  - To determine the function and mechanism of action of the 8S-lipoxygenase (8-LOX)
      product of arachidonic acid, 8S-hydroxyeicosatetraenoic acid (8S-HETE), which is
      normally synthesized only after irritation of the epidermis, transgenic mice with
      8-LOX targeted to keratinocytes through the use of a loricrin promoter were
      generated. Histological analyses showed that the skin, tongue, and stomach of
      transgenic mice are highly differentiated, and immunoblotting and
      immunohistochemistries of skin showed higher levels of keratin-1 expression
      compared with wild-type mice. The labeling index, however, of the transgenic
      epidermis was twice that of the wild-type epidermis. Furthermore, 8S-HETE
      treatment of wild-type primary keratinocytes induced keratin-1 expression.
      Peroxisome proliferator activated receptor alpha (PPARalpha) was identified as a
      crucial component of keratin-1 induction through transient transfection with
      expression vectors for PPARalpha, PPARgamma, and a dominant-negative PPAR, as
      well as through the use of known PPAR agonists. From these studies, it is
      concluded that 8S-HETE plays an important role in keratinocyte differentiation
      and that at least some of its effects are mediated by PPARalpha.

PMID- 10965850
TI  - Regulated Ran-binding protein 1 activity is required for organization and
      function of the mitotic spindle in mammalian cells in vivo.
AB  - Ran-binding protein (RanBP) 1 is a major regulator of the Ran GTPase and is
      encoded by a regulatory target gene of E2F factors. The Ran GTPase network
      controls several cellular processes, including nucleocytoplasmic transport and
      cell cycle progression, and has recently also been shown to regulate microtubule
      nucleation and spindle assembly in Xenopus oocyte extracts. Here we report that
      RanBP1 protein levels are cell cycle regulated in mammalian cells, increase from
      S phase to M phase, peak in metaphase, and abruptly decline in late telophase.
      Overexpression of RanBP1 throughout the cell cycle yields abnormal mitoses
      characterized by severe defects in spindle polarization. In addition,
      microinjection of anti-RanBP1 antibody in mitotic cells induces mitotic delay and
      abnormal nuclear division, reflecting an abnormal stabilization of the mitotic
      spindle. Thus, regulated RanBP1 activity is required for proper execution of
      mitosis in somatic cells.

PMID- 10965851
TI  - Accommodating learning-disabled students.

PMID- 10965852
TI  - Comments on "a thorough pulmonary exam...".

PMID- 10965853
TI  - Use of videoconferencing for residency interviews.

PMID- 10965854
TI  - The nation's changing Needs for Biomedical and Behavioral Scientists.

PMID- 10965855
TI  - The decade of the nineties at the UCLA Medical Center: responses to dramatic
      marketplace changes.
AB  - The evolution of the health care marketplace in the nineties in Southern
      California is described, including the dominance of managed care at the decade's
      end. The marketplace, especially in Los Angeles, is now one of the most complex,
      competitive, and challenging medical marketplaces in the country. The University
      of California, Los Angeles (UCLA) Medical Center and the academic health center
      of which it is a part have had to respond appropriately and vigorously to survive
      and to position themselves for the future. This article focuses on the responses
      of the medical center to these marketplace pressures. The center has recognized
      single-signature contracting, cost containment, and an emphasis on ambulatory
      care as fundamental success factors for survival in a complex, organized managed
      care environment. Data on the medical, financial, and educational performances of
      the medical center are presented in terms of its responses to the marketplace.
      Preliminary information about quality of care is presented for three patient
      population groups that have been heavily affected by managed care. The need for
      emphasis on quality and service for future success and the attendant need for
      emphasis on information systems are discussed. The importance of fundamental
      understanding of markets is also reviewed. The concomitant approaches to securing
      the center's academic missions are described, including changes in institutional
      governance for the entire health sciences center of which the medical center is a
      part and the establishment of priorities in research, clinical care, and teaching
      programs, especially teaching programs in primary care.

PMID- 10965856
TI  - Interprofessional education in ethics at an academic health sciences center.
AB  - The authors relate their experiences with interprofessional teaching of ethics at
      the University of Colorado Health Sciences Center, describing the history,
      planning, content, and structure of a required ethics course and discussing its
      role in the institution's plan to create more interprofessional education
      opportunities. The authors describe both the benefits of teaching ethics on an
      interprofessional basis and the challenges they encountered in launching the
      course. Challenges included responding to diverse and divergent faculty and
      student reactions, controlling a curriculum across schools, and learning how to
      think about education in interprofessional rather than profession-specific ways.
      Included in the discussion are the results obtained with various evaluation tools
      designed and assessed by the Office of Education on the campus, to which students
      and faculty responded the first time the course was offered.

PMID- 10965857
TI  - The difficulty of sustaining curricular reforms: a study of "drift" at one
      school.
AB  - In 1997, five years after a major curricular reform at the University of Michigan
      Medical School, the authors revisited the Goals for Medical Education (written by
      faculty to guide the reform process) to identify factors that had facilitated or
      hindered their achievement. By reviewing responses to identical questionnaires
      circulated to faculty in 1993 and again in 1997, they learned that considerably
      more lectures were being used to deliver curricular content in the first-year
      curriculum than the faculty thought was ideal, and that less social science,
      humanities, and ethics material was being presented in the first year than the
      faculty thought was ideal. The authors also learned that consensus between
      faculty basic scientists and faculty clinicians about the content that would make
      up an ideal first-year curriculum had diverged since adoption of the new
      curriculum. Movement toward decreasing the amounts of social sciences,
      humanities, and ethics in the first year of medical school was particularly
      pronounced among the basic scientists, who felt this material was being taught
      prematurely and at the expense of essential basic science content. In contrast,
      by 1997 much closer agreement had developed between the two groups regarding time
      they would allocate for lectures; this agreement unfortunately reflected a
      stagnation in the adoption of active learning methods. Movement toward increasing
      the amount of time for lectures in the first-year curriculum was particularly
      pronounced among the clinicians, who reported feeling more and more pressured to
      bring in clinical revenues. Based on faculty comments and the school's experience
      with centralized governance and centralized funding, the authors propose a direct
      linkage between institutional funding to departments and the teaching effort of
      faculty in the departments, and sufficient, centralized funding to relieve
      pressure on faculty and to foster educational creativity. They maintain that this
      may be the most effective way to guarantee ongoing innovation, support
      interdisciplinary teaching, and subsequently move the curriculum and teachers
      completely away from content that is isolated within traditional department
      structures. At the same time they acknowledge that changing faculty attitudes
      presents a challenge.

PMID- 10965858
TI  - Beyond affirmative action: one school's experiences with a race-neutral admission
      process.
AB  - The authors first review the national debate about affirmative action programs,
      examine the results of these programs in higher education, and present data from
      1995 through 1999 for minority enrollment in U.S., California, and Texas medical
      schools. Population projections for the state of Texas indicate a national trend
      that minority groups will outnumber the current majority early in the new
      millennium. A brief review of studies of the practice patterns of minority
      physicians concludes that minority physicians serve patients of their own races
      and/or ethnicities, poor patients, and Medicaid patients in disproportion to
      their numbers. This rationale, as well as the humanitarian need to develop all
      persons to their highest potential, led the Texas A&M University Health Science
      Center College of Medicine to develop a race-neutral process for admission.
      Changes in the admission process are described and preliminary results are
      presented. This article is written to stimulate other medical colleges to engage
      in an ongoing dialog about admission criteria and processes that can effectively
      select applicants who fit the mission of each medical college and who, as
      physicians, will care for patients who are members of this country's burgeoning
      minority groups.

PMID- 10965859
TI  - Decision sciences and evidence-based medicine--two intellectual movements to
      support clinical decision making.

PMID- 10965860
TI  - The need for a knowledge system in sleep and chronobiology.

PMID- 10965861
TI  - Medicine and the arts. The death of the hired man.

PMID- 10965862
TI  - A comparative study of measures to evaluate medical students' performance.
AB  - PURPOSE: To assess how new National Board of Medical Examiners (NBME) performance
      examinations--computerbased case simulations (CBX) and standardized patient exams
      (SPX)-compare with each other and with traditional internal and external measures
      of medical students' performances. Secondary objectives examined attitudes of
      students toward new and traditional evaluation modalities. METHOD: Fourth-year
      students (n = 155) at the University of California, Los Angeles, School of
      Medicine (including joint programs at Charles R. Drew University of Medicine and
      Science and University of California, Riverside) were assigned two days of
      performance examinations (eight SPXs, ten CBXs, and a self-administered
      attitudinal survey). The CBX was scored by the NBME and the SPX by a NBME/Macy
      consortium. Scores were linked to the survey and correlated with archival student
      data, including traditional performance indicators (licensing board scores, grade
      point averages, etc.). RESULTS: Of the 155 students, 95% completed the testing.
      The CBX and the SPX had low to moderate statistically significant correlations
      with each other and with traditional measures of performance. Traditional
      measures were intercorrelated at higher levels than with the CBX or SPX.
      Students' perceptions of the various evaluation methods varied based on the
      assessment. These findings are consistent with the theoretical construct for
      development of performance examinations. For example, to assess clinical decision
      making, students rated the CBX best, while they rated multiple-choice
      examinations best to assess knowledge. CONCLUSION: Examination results and
      student perception studies provide converging evidence that performance
      examinations measure different physician competency domains and support using
      multipronged assessment approaches.

PMID- 10965863
TI  - Medical students' cases as an empirical basis for teaching clinical ethics.
AB  - PURPOSE: To identify ethical issues that interns encounter in their clinical
      education and thus build a more empirical basis for the required contents of the
      clinical ethics curriculum. METHOD: The authors analyzed a total of 522 required
      case reports on ethical dilemmas experienced by interns from September 1995 to
      May 1999 at the medical school of Vrije Universiteit in Amsterdam. They
      identified four regularly described and numerous less frequently described
      topics. RESULTS: The interns addressed a wide range of ethical themes. In 45% of
      the cases, they mentioned disclosure or non-disclosure of information and
      informed consent; in 37%, medical decisions at the end of life; in 16%, medical
      failures; and in 9%, problems transferring patients from one caregiver to
      another. The interns also identified 27 themes linked to their unique position as
      interns and 19 themes related to specific types of patients. CONCLUSION: Based on
      self-reported experiences, the authors conclude that clinical ethics teachers
      should reflect on a multitude of dilemmas. Special expertise is required with
      respect to end-of-life decisions, truth telling, medical failures, and
      transferring patients from one caregiver to another. The clinical ethics
      curriculum should encourage students to voice their opinions and deal with
      values, responsibilities, and the uncertainty and failings of medical
      interventions.

PMID- 10965864
TI  - Framing procedural risks to patients: is 99% safe the same as a risk of 1 in 100?
AB  - PURPOSE: A patient's willingness to consent to a procedure may be influenced by
      various factors, including the patient's rapport with the physician, nonverbal
      cues he or she receives during the discussion of risks, and other elements of the
      discussion of risks. Previous reports address these influences, but the effect of
      the actual wording used to describe risks is unclear. The purpose of this study
      was to better understand how framing the risk involved in a procedure affects a
      patient's likelihood to consent to the procedure. METHOD: In a 1997 study at the
      Cleveland Clinic Foundation, the authors randomly assigned 116 patients to view
      one of two short videos describing angioplasty and its associated risks. Sixty
      three participants viewed the first video, which framed the procedure as 99%
      safe, and 53 viewed the second, which framed the likelihood of complication as 1
      in 100. Participants were then asked to rate their consent to two hypothetical
      treatment scenarios on a four-point Likert-type scale (1 = definitely, 4 =
      definitely not). RESULTS: When asked to consent to a treatment scenario that
      would relieve chest pain but offer no survival benefit, respondents who viewed
      the first video were more likely to consent than were those who viewed the second
      (p<.001). There was no significant difference in the two groups' likelihoods to
      consent when the potential health benefit was to reduce the risk of future heart
      attack. CONCLUSION: This study's finding provides evidence that how a physician
      describes a procedure's risks when obtaining a patient's informed consent
      significantly influences the likelihood of consent. This fact should be
      considered when teaching communication skills, including interviewing and patient
      education skills, so that patients will be more likely to make health care
      decisions that are consistent with their own values and beliefs.

PMID- 10965865
TI  - How medical students and residents describe the roles and characteristics of
      their influential clinical teachers.
AB  - PURPOSE: This study sought to identify students' perceptions about
      characteristics of faculty who had positively influenced their clinical education
      and to determine whether the students' perceptions matched those published for
      residents. METHOD: On exit surveys in 1997 and 1998, students graduating from
      Baylor College of Medicine were asked to list clinical faculty who had
      "significantly and positively influenced their clinical education" and to
      describe that influence. Using codes derived from Ullian's earlier 1994 study
      regarding residents' perceptions, the authors classified 1,153 written
      descriptions that expressed a single characteristic or teacher attribute into
      five roles: person, physician, supervisor, teacher, and unspecified (global). For
      each role, categories expressing similar characteristics were grouped into
      clusters. Although one author coded all descriptions, interrater reliability
      (.93) was determined by having an assistant code a set of randomly selected
      descriptions. RESULTS: The medical students ranked characteristics of the teacher
      role highest. In contrast, Ullian's residents ranked characteristics of the
      supervisor role highest. CONCLUSION: Medical students and residents differ
      substantially in their perceptions of the roles and characteristics of their
      influential clinical teachers. The results in this study corroborate Stritter's
      learning vector theory. Thus, learners' perceptions of the value of their
      teachers' behaviors change during their professional development. These
      perceptual changes may explain why medical students and residents assess the same
      faculty's teaching very differently. These results also support the need to
      prepare clinical faculty differently for working with medical students as
      compared with residents.

PMID- 10965866
TI  - Institutional policies of U.S. medical schools regarding tenure, promotion, and
      benefits for part-time faculty.
AB  - PURPOSE: To collect data on institutional policies regarding tenure, promotions,
      and benefits for part-time faculty at U.S. medical schools and determine the
      extent to which part-time work is a feasible or attractive option for academic
      physicians. METHOD: In July 1996, the authors sent a 29-item questionnaire
      regarding tenure, promotions, and benefit policies for part-time faculty to
      respondents identified by the deans' offices of medical schools in the United
      States and Puerto Rico. Responses were analyzed using descriptive statistics and
      chi-square analyses. RESULTS: Respondents from 104 of 126 medical schools (83%)
      completed the questionnaire; 58 responded that their schools had written policies
      about tenure, promotion, or benefits for part-time faculty. Tenure. Of the 95
      medical schools with tenure systems, 25 allowed part-time faculty to get tenure
      and 76 allowed for extending the time to tenure. Allowable reasons to slow the
      tenure clock included medical leave (65), maternity leave (65), paternity leave
      (54), other leave of absence (59). Only 23 allowed part-time status as a reason
      to slow the tenure clock. Policies written by the dean's office and from schools
      in the midwest or west were more favorable to part-time faculty's being allowed
      to get tenure. Promotions. The majority of respondents reported that it was
      possible for part-time faculty to serve as clinical assistant, assistant,
      associate, and full professors. Benefits. The majority of schools offered
      retirement benefits and health, dental, disability, and life insurance to part
      time faculty, although in many cases part-time faculty had to buy additional
      coverage to match that of full-time faculty. CONCLUSIONS: Most medical schools do
      not have policies that foster tenure for part-time faculty, although many allow
      for promotion and offer a variety of benefits to part-time faculty.

PMID- 10965867
TI  - Knowledge, attitudes, and behaviors of Alabama's primary care physicians
      regarding cancer genetics.
AB  - PURPOSE: To determine Alabama's primary care physicians' knowledge, attitudes,
      and behaviors regarding cancer genetics. METHOD: A questionnaire was mailed to a
      random sample of 1,148 physicians: family and general practitioners, internists,
      and obstetrician-gynecologists. RESULTS: Of the surveyed physicians, 22.1%
      responded. Of the respondents, 63% to 85% obtained family histories of cancer
      from 76% to 100% of their patients. Obstetrician-gynecologists referred more
      patients for cancer genetic testing (p = .008) and were more confident in their
      abilities to tailor preventive recommendations based on the results (p = .05)
      than were the other physicians. Primary care physicians were more likely than
      were obstetrician-gynecologists to identify lack of time during the patient visit
      as hindering efforts to do genetic counseling (p = .01). Physicians in practice
      for ten years or less were more confident in explaining genetic test results than
      were those in practice for more than 20 years (p = .01). CONCLUSION: These data
      validate gaps in primary care practices in obtaining family history of cancer, as
      well as lack of confidence in explaining genetic test results and in tailoring
      recommendations based on the tests.

PMID- 10965869
TI  - "Advising Oliver Mann"--a case-based, small-group orientation to medical school.
AB  - In 1998, the authors implemented a new academic orientation built around a
      problem-based clinical exercise for entering medical students, to prepare them
      for a curriculum emphasizing active learning in small groups. The exercise
      enables students to begin their professional studies with a "hands on"
      understanding of two major emphases of the curriculum: (1) the process of small
      group learning that will guide their medical education and (2) the principles of
      patient care that will guide their future practice of medicine. Called "Advising
      Oliver Mann," this orientation presents students with a clinical problem that
      they must work in small groups to solve. By collaborating in teams of ten, they
      become acquainted with the small-group learning methods at the heart of the
      school's curriculum. Through solving a clinical problem, they discover vital
      principles of patient care, such as the need in clinical decision making to
      integrate the scientific perspective with the perspective of patient and family.
      In developing "Oliver Mann," the authors came to realize that orientations can be
      much more than introductions. They can be reflective moments in a busy
      curriculum, a time for students and faculty to step back and take stock of
      important issues in education and doctoring. The authors are currently
      experimenting with exercises linking their freshman orientation with orientations
      in the second and third years so participants can reflect on the challenges of
      each new year and carry forward the small-group methods and practice of medicine
      themes of the new curriculum.

PMID- 10965868
TI  - The pediatric intern retreat: 20-year evolution of a continuing investment.
AB  - For the past 22 years the interns in pediatrics at the University of Washington
      and Children's Hospital and Regional Medical Center have been relieved of all
      clinical duties in order to participate in a five-day retreat. The retreat
      provides an opportunity for the interns to learn more about their classmates,
      build stronger bonds, and provide mutual support. This retreat has been supported
      by the hospital, the department of pediatrics, faculty, fellows, and community
      physicians. The authors describe the history of the Intern Retreat, present its
      goals, daily activities, and faculty, and discuss how the retreat is funded and
      supported by the hospital and the medical community.

PMID- 10965870
TI  - The German medical dissertation--time to change?
AB  - German medical students must conduct a research project and write a dissertation
      in order to receive the title "Doctor." However, the dissertation is not required
      to graduate, enter a residency, or practice medicine. About 90% of practicing
      physicians hold the title "Doctor"; a career in academic medicine almost always
      requires it. Although no convincing evidence supports the usefulness of the
      dissertation, many regard its completion as important to maintaining a high level
      of scientific competence and patient care. In recent years, the number of
      successfully completed dissertations has declined. Lack of time during medical
      school, the perceived irrelevance of the dissertation to medical practice, and
      the poor design of many projects may be at least part of the problem. There is
      also increasing evidence that conducting research frequently delays graduation
      and may affect clinical skills because students working on projects attend fewer
      classes, ward rounds, and clinical tutorials and do not spent sufficient time
      preparing for examinations. The scientific value of students' research has also
      been criticized; critics point out that students do not have enough time or
      experience to critically analyze methods and data, and they often are not
      properly supervised. European unification will probably lead to standardized
      requirements for medical education and research. The authors hope this will
      eliminate the dissertation requirement in Germany.

PMID- 10965871
TI  - A new database for tissue-specific gene expression and function in the ovary.

PMID- 10965872
TI  - The Ovarian Kaleidoscope database: an online resource for the ovarian research
      community.
AB  - The Ovarian Kaleidoscope database (OKdb) is a collaborative online resource for
      scientists investigating the ovary. It provides information regarding the
      biological function, expression pattern, and regulation of genes expressed in the
      ovary as well as for the phenotypes associated with their mutation. In addition,
      the records in the OKdb are linked to other sites offering online information
      about biomedical publications, nucleotide and amino acid sequences, and human
      genes and genetic disorders. A powerful search tool allows the retrieval of
      records for specific genes and gene products based on their properties at the
      molecular, cellular, ovarian, or organism level. Researchers working on
      particular aspects of ovarian physiology can submit information into the database
      through a simple web-based form and instantly update their records as additional
      data become available. Because of this approach, the OKdb website could serve as
      a tool with which to navigate through the rapidly expanding amount of information
      about the expression and function of individual genes in the ovary and could also
      enhance communication within the ovarian research community. Moreover, the design
      of the OKdb could serve as a model for the development of other online databases
      of tissue-specific gene expression and function. The OKdb can be accessed at
      http://ovary.stanford.edu/.

PMID- 10965873
TI  - A sweetheart deal for thyroid hormone.

PMID- 10965874
TI  - The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects
      plasma lipids and cardiac activity.
AB  - Thyroid hormones influence the function of many organs and mediate their diverse
      actions through two types of thyroid hormone receptors, TRalpha and TRbeta.
      Little is known about effects of ligands that preferentially interact with the
      two different TR subtypes. In the current study the comparison of the effects of
      the novel synthetic TRbeta-selective compound GC-1 with T3 at equimolar doses in
      hypothyroid mice revealed that GC-1 had better triglyceride-lowering and similar
      cholesterol-lowering effects than T3. T3, but not GC-1, increased heart rate and
      elevated messenger RNA levels coding for the I(f) channel (HCN2), a cardiac
      pacemaker that was decreased in hypothyroid mice. T3 had a larger positive
      inotropic effect than GC-1. T3, but not GC-1, normalized heart and body weights
      and messenger RNAs of myosin heavy chain alpha and beta and the sarcoplasmic
      reticulum adenosine triphosphatase (Serca2). Additional dose-response studies in
      hypercholesteremic rats confirmed the preferential effect of GC-1 on TRbeta
      mediated parameters by showing a much higher potency to influence cholesterol and
      TSH than heart rate. The preferred accumulation of GC-1 in the liver vs. the
      heart probably also contributes to its marked lipid-lowering effect vs. the
      absent effect on heart rate. These data indicate that GC-1 could represent a
      prototype for new drugs for the treatment of high lipid levels or obesity.

PMID- 10965875
TI  - Soluble factors guide gonadotropin-releasing hormone axonal targeting to the
      median eminence.
AB  - Axons of GnRH neurons terminate at the median eminence in the medial basal
      hypothalamus (MBH) of the brain early in development. Similarly, GnRH neurons in
      grafts of preoptic area (POA) tissue within the third ventricle of hypogonadal
      mice preferentially innervate the median eminence. Organotypic cocultures of POA
      explants with other neural tissues suggest that a soluble substance(s) derived
      from the MBH may be directing this targeting. To begin to identify diffusable
      chemoattractants, we used preincubated heparin-coated acrylic beads to present
      specific solutes to POA explants on collagen- and laminin-coated membranes in
      insert chambers. GnRH axons grew on the membrane in greater number and with
      longer axons toward conditioned medium from MBH cultures than on the side away
      from the beads (P < 0.01). In contrast, GnRH axons showed no preferential
      outgrowth when incubated with beads soaked in control, defined medium. The
      attraction of MBH-conditioned medium was not generalizable to all neuroendocrine
      neurons, as it was not seen for galanin immunoreactive outgrowth from POA
      explants. There also were more GnRH axons toward conditioned medium from mouse
      brain microvascular endothelial cells, but no difference in axon length. Basic
      fibroblast growth factor (bFGF), a component of both endothelial cells and
      ventricular tanycytes, significantly attracted more and longer GnRH axons. Thus,
      bFGF may be one of the soluble factors directing GnRH outgrowth to the median
      eminence. However, as with so many other redundancies in the reproductive system,
      it is unlikely that it is the only targeting factor, as bFGF knockout mice are
      reported to be reproductively competent.

PMID- 10965876
TI  - The central melanocortin system can directly regulate serum insulin levels.
AB  - The central melanocortin system has been demonstrated to play a pivotal role in
      energy homeostasis. Genetic disruption of this system causes obesity in both
      humans and mice. Previous experiments have shown that centrally-administered
      melanocortin agonists inhibit food intake and stimulate oxygen consumption. Here
      we report that centrally-administered melanocortin agonists also inhibit basal
      insulin release, and alter glucose tolerance. Furthermore, increased plasma
      insulin levels occur in the young lean MC4-R knockout (MC4-RKO) mouse, and
      impaired insulin tolerance takes place before the onset of detectable hyperphagia
      or obesity. These data suggest that the central melanocortin system regulates not
      only energy intake and expenditure, but also processes related to energy
      partitioning, as indicated by effects on insulin release and peripheral insulin
      responsiveness. Previous studies emphasize the role of excess adipose mass in the
      development of tissue insulin resistance, leading to type II diabetes. The data
      presented here show that defects in the central control of glucose homeostasis
      may be an additional factor in some types of obesity-associated type II diabetes.

PMID- 10965877
TI  - Evaluating the ligand specificity of zebrafish parathyroid hormone (PTH)
      receptors: comparison of PTH, PTH-related protein, and tuberoinfundibular peptide
      of 39 residues.
AB  - Homologs of mammalian PTH1 and PTH2 receptors, and a novel PTH3 receptor have
      been identified in zebrafish (zPTH1, zPTH2, and zPTH3). zPTH1 receptor ligand
      specificity is similar to that of mammalian PTH1 receptors. The zPTH2 receptor is
      selective for PTH over PTH-related protein (PTHrP); however, PTH produces only
      modest cAMP accumulation. A PTH2 receptor-selective peptide, tuberoinfundibular
      peptide of 39 residues (TIP39), has recently been purified from bovine
      hypothalamus. The effect of TIP39 has not previously been examined on zebrafish
      receptors. The zPTH3 receptor was initially described as PTHrP selective based on
      comparison with the effects of human PTH. We have now examined the ligand
      specificity of the zebrafish PTH-recognizing receptors expressed in COS-7 cells
      using a wide range of ligands. TIP39 is a potent agonist for stimulation of cAMP
      accumulation at two putative splice variants of the zPTH2 receptor (EC50, 2.6 and
      5.2 nM); in comparison, PTH is a partial agonist [maximal effect (Emax) of PTH
      peptides ranges from 28-49% of the TIP39 Emax]. As TIP39 is much more efficacious
      than any known PTH-like peptide, a homolog of TIP39 may be the zPTH2 receptor's
      endogenous ligand. At the zPTH3 receptor, rat PTH-(1-34) and rat PTH-(1-84)
      (EC50, 0.22 and 0.45 nM) are more potent than PTHrP (EC50, 1.5 nM), and rPTH-(1
      34) binds with high affinity (3.2 nM). PTH has not been isolated from fish. PTHrP
      like peptides, which have been identified in fish, may be the natural ligands for
      zPTH1 and zPTH3 receptors.

PMID- 10965878
TI  - Gonadotropin-releasing hormone receptor activation of extracellular signal
      regulated kinase and tyrosine kinases in transfected GH3 cells and in alphaT3-1
      cells.
AB  - GH3 cells were stably transfected with the wild-type murine GnRH receptor and a
      clonal cell line selected on the basis of inositol phosphate production and
      PRL/GH release in response to GnRH. This cell line (wt28) was characterized by
      [125I]GnRH analog binding, [3H]inositol phosphate response to GnRH, and hormone
      secretion. We examined the activation of the mitogen-activated protein kinase
      isoforms, extracellular signal-regulated kinase 1/2 (ERK1/2) and tyrosine kinases
      in wt28 cells and alphaT3-1 cells (which express a native GnRH) using specific
      phospho-ERK1/2 and phosphotyrosine antibodies. Concentration-response and time
      course data revealed that a sustained ERK1/2 response was seen only in aT3-1
      cells. Furthermore, GnRH-induced tyrosine phosphorylation was detectable in
      alphaT3-1 cells, but not in wt28 cells. Activators for several different
      signaling pathways revealed distinct differences between the cell types. Protein
      kinase C activation by phorbol 12,13-dibutyrate was very effective in alphaT3-1
      cells at phosphorylation of both ERK1/2 and tyrosine, whereas raising cAMP levels
      using forskolin also strongly increased wt28 cell ERK1/2 phosphorylation. Only
      the tyrosine phosphatase inhibitor pervanadate increased tyrosine phosphorylation
      in wt28 cells. The lack of sustained ERK1/2 phosphorylation in wt28 cells could
      be the result of minimal tyrosine kinase activation by GnRH compounded by a
      different pathway profile for ERK1/2 activation. When pervanadate and GnRH were
      combined, ERK1/2 phosphorylation was synergistic and sustained in wt28 cells,
      whereas the response was additive in alphaT3-1 cells. In sum, the intracellular
      pathways leading to ERK1/2 and tyrosine phosphorylation in alphaT3-1 and wt28
      cells are distinct; thus, activating GnRH receptors in each of the two cell types
      leads to different sequelae of events regarding ERK1/2 activation.

PMID- 10965880
TI  - Differential regulation of insulin-like growth factor-binding protein-3 protease
      activity in MCF-7 breast cancer cells by estrogen and transforming growth factor
      beta1.
AB  - We have examined the regulation of an insulin-like growth factor-binding protein
      3 (IGFBP-3) protease secreted by MCF-7 human breast cancer cells using a ligand
      binding assay that relies on the decrease in affinity for des(1-3)IGF-I that
      occurs when IGFBP-3 becomes proteolyzed. IGFBP-3 protease activity was not
      altered by treatment of MCF-7 cells with all-trans-retinoic acid, vitamin D,
      epidermal growth factor, platelet-derived growth factor, insulin, or forskolin.
      However, estradiol was a potent stimulator of IGFBP-3 protease activity, with a
      significant and maximal effect at 1 nM. This was prevented by cotreatment with
      tamoxifen, which had no significant effect in the absence of estradiol. By
      contrast, TGFbeta1 dose dependently inhibited the amount of protease activity
      secreted by MCF-7 cells, with complete reversal of IGFBP-3 degradation apparent
      in response to 10 ng/ml TGFbeta1. This study has demonstrated that estrogens and
      TGFbeta1, factors that are stimulatory and inhibitory, respectively, for MCF-7
      cell growth, also stimulate and inhibit the production of an enzyme capable of
      proteolyzing the growth inhibitory protein IGFBP-3.

PMID- 10965879
TI  - Insulin-like growth factor (IGF) binding protein-3 potentiation of IGF action is
      mediated through the phosphatidylinositol-3-kinase pathway and is associated with
      alteration in protein kinase B/AKT sensitivity.
AB  - Cell-association and processing of insulin-like growth factor binding protein-3
      (IGFBP-3) by cultured bovine fibroblasts results in markedly enhanced type I IGF
      receptor signaling at a step distal to ligand binding. The purpose of the present
      study was to determine the intracellular mediators of IGFBP-3's potentiating
      effect. Preincubation of cultured bovine fibroblasts with 50 nM IGFBP-3 had no
      effect alone, but enhanced by 3- to 4-fold IGF-I-stimulated 3H-aminoisobutryric
      acid (AIB) uptake. IGFBP-3-induced potentiation was specifically prevented if an
      inhibitor of phosphatidylinositol 3 (PI3)-kinase activation (LY294002), but not
      an inhibitor of mitogen-activated protein kinase activation (PD98059), was
      present during the preincubation period. IGFBP-3 did not directly activate the
      downstream effector of PI3-kinase, protein kinase B (PKB)/Akt. However, the
      sensitivity of PKB/Akt to activation by IGF-I was increased by 2- to 4-fold with
      IGFBP-3 pretreatment. This increased sensitivity was accompanied by altered
      mobility of PKB/Akt on SDS-polyacrylamide gels, suggestive of a diminished
      phosphorylation state. Consistent with this, okadaic acid, a potent
      serine/threonine phosphatase inhibitor, was able to block the potentiation effect
      of IGFBP-3 and prevent the altered mobility of the PKB/Akt molecule in response
      to IGFBP-3 treatment. PKB/Akt immunoprecipitated from IGFBP-3-pretreated cells
      was no longer recognized by an antibody specific for phosphorylated threonine
      followed by proline. These data indicate that IGFBP-3 modulates type I IGF
      receptor signaling through an effect on PI-3-kinase pathway substrates and
      suggest a novel mechanism of dephosphorylation whereby PKB/Akt is transformed
      into a more sensitive substrate of type I IGF receptor signaling.

PMID- 10965881
TI  - Nongenomic actions of testosterone on a subset of lactotrophs in the male rat
      pituitary.
AB  - Rapid, nongenomic effects of testosterone on PRL release in vitro were
      investigated. Anterior pituitary tissue from adult male rats was stimulated in
      vitro for 5 or 20 min with testosterone (T; 1 or 100 nM) or testosterone-BSA (T
      BSA; 1 or 100 nM) with or without 1.2 mM tannic acid, which enables visualization
      of secretory granule exocytosis. Within 5 min, both concentrations of T and T-BSA
      stimulated exocytosis from type 2 lactotrophs (characterized by small spherical
      granules), but not from type 1 lactotrophs (characterized by large polymorphic
      granules). The effects of T on type 2 lactotrophs could be blocked by
      preincubation with dopamine (500 nM), but were not time or concentration
      dependent, and could not be inhibited by 1) removal of extracellular Ca2+, 2) the
      L-type Ca2+ channel blocker nifedipine (100 nM), 3) the Ca2+-adenosine
      triphosphatase inhibitor thapsigargin (150 nM), 4) the PKC inhibitor retinal (10
      microM), or 5) the gamma-aminobutyric acidA chloride channel blocker picrotoxin
      (100 microM). T-BSA (0.1 nM to 1 microM) for 5 or 20 min also caused an increased
      release of immunoreactive PRL into the medium compared with control incubations.
      T and T-BSA did not stimulate exocytosis from gonadotrophs or cause LH release.
      In conclusion, we report for the first time a rapid, nongenomic effect of T on
      PRL secretion.

PMID- 10965882
TI  - Involvement of reactive oxygen species in the activation of tyrosine kinase and
      extracellular signal-regulated kinase by angiotensin II.
AB  - Reactive oxygen species (ROS) have been proposed to mediate vascular hypertrophy
      induced by angiotensin II (Ang II). Recently, we and others have shown that
      growth-promoting signals by Ang II involve protein tyrosine kinase (PTK) and
      extracellular signal-regulated kinase (ERK). However, whether ROS contribute to
      the Ang II-induced PTK and/or ERK activation in vascular smooth muscle cells
      (VSMCs) remains largely unclear. Here, we have investigated the possible
      involvement of ROS in Ang II-induced PTK and ERK activation. In the presence of a
      NADH/NADPH oxidase inhibitor, diphenyleneiodonium (DPI) or an antioxidant, alpha
      tocopherol, Ang II-induced protein tyrosine phosphorylation of two major proteins
      (p120, p70) and ERK activation were markedly reduced, whereas ERK activation by
      epidermal growth factor was unaffected. DPI also inhibited Ang II-induced H2O2
      production and PTK activation. In this regard, H2O2 and a membrane permeable
      thiol-oxidizing agent, diamide, stimulated protein tyrosine phosphorylation of
      p120 and p70, and ERK activation in VSMCs. H2O2 also enhanced PTK activity. From
      these data, we conclude that ROS play a critical role in the Ang II-induced PTK
      and ERK activation in VSMCs, thereby contributing to vascular growth associated
      with enhanced Ang II activity.

PMID- 10965884
TI  - The peroxisome proliferator perfluorodecanoic acid inhibits the peripheral-type
      benzodiazepine receptor (PBR) expression and hormone-stimulated mitochondrial
      cholesterol transport and steroid formation in Leydig cells.
AB  - The peroxisome proliferator perfluordecanoic acid (PFDA) has been shown to exert
      an antiandrogenic effect in vivo by acting directly on the interstitial Leydig
      cells of the testis. The objective of this study was to examine the in vitro
      effects of PFDA and identify its site of action in steroidogenesis using as model
      systems the mouse tumor MA-10 and isolated rat Leydig cells. PFDA inhibited in a
      time- and dose-dependent manner the hCG-stimulated Leydig cell steroidogenesis.
      This effect was localized at the level of cholesterol transport into the
      mitochondria. PFDA did not affect either the total cell protein synthesis or the
      mitochondrial integrity. Moreover, it did not induce any DNA damage.
      Morphological studies indicated that PFDA induced lipid accumulation in the
      cells, probably due to the fact that cholesterol mobilized by hCG did not enter
      the mitochondria to be used for steroidogenesis. In search of the target of PFDA,
      we examined its effect on key regulatory mechanisms of steroidogenesis. PFDA did
      not affect the hCG-induced steroidogenic acute regulatory protein (StAR) levels.
      However, it was found to inhibit the mitochondrial peripheral-type benzodiazepine
      receptor (PBR) ligand binding capacity, 18-kDa protein, and messenger RNA (mRNA)
      levels. Further studies indicated that PFDA did not affect PBR transcription, but
      it rather accelerated PBR mRNA decay. Taken together, these data suggest that
      PFDA inhibits the Leydig cell steroidogenesis by affecting PBR mRNA stability,
      thus inhibiting PBR expression, cholesterol transport into the mitochondria, and
      the subsequent steroid formation. Moreover, this action of PFDA on PBR mRNA
      stability indicates a new mechanism of action of peroxisome proliferators
      distinct from the classic transcription-mediated regulation of target genes.

PMID- 10965883
TI  - Fibroblast growth factor-2 inhibits the maturation of pro-insulin-like growth
      factor-II (Pro-IGF-II) and the expression of insulin-like growth factor binding
      protein-2 (IGFBP-2) in the human adrenocortical tumor cell line NCI-H295R.
AB  - The IGF system is thought to play a major role in adrenocortical tumorigenesis.
      In this study, we used the NCI H295R cell line as a model to investigate the
      effects of fibroblast growth factor-2 (FGF-2), a potent mitogen for normal
      adrenal cells, on the proliferation and on the expression of the IGF system in
      cultured adrenocortical tumor cells. Three immunoreactive FGF-2 isoforms of
      molecular masses 18, 22, and 24 kDa were detected in H295R cell extracts.
      Recombinant human FGF-2 stimulated the proliferation of adrenocortical tumor
      cells in a dose- and time-dependent manner, with a maximal effect at a
      concentration of about 1 ng/ml. Treatment of H295R cells with 10 ng/ml FGF-2 for
      7 days had no significant effect on IGF-II messenger RNA levels. However, a
      marked increase in levels of intracellular IGF-II protein was detected by
      immunoblotting. In contrast, FGF-2 induced a marked decrease in the amount of IGF
      II protein secreted, with the disappearance of mature IGF-II and secretion of
      higher molecular forms of the growth factor, suggesting modifications of IGF-II
      processing. Cell cultures in the presence of brefeldin A (1 microg/ml), a
      specific inhibitor of protein secretion, suggested that FGF-2 did not increase
      IGF-II synthesis but instead inhibited the secretion of pro-IGF-II from H295R
      cells, thereby impairing the final steps of IGF-II processing to the mature 7.5
      kDa peptide. At the same concentrations, FGF-2 also decreased both IGFBP-2
      messenger RNA and secreted protein, which might increase IGF-II bioavailability.
      No proteolysis of IGFBP-2 was detected in FGF-2-conditioned medium. Altogether,
      these results indicate that FGF-2 is mitogenic for NCI H295R tumor cells and
      regulates the expression of both IGF-II and IGFBP-2 in this tumor model.
      Moreover, this study shows a novel effect of FGF-2, by which this growth factor
      modulates the processing of pro-IGF-II.

PMID- 10965885
TI  - Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I),
      impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in
      adult female rats.
AB  - Dietary protein deficiency, common in elderly, is associated with decreased areal
      bone mineral density and plasma insulin-like growth factor I (IGF-I). To
      investigate the early adaptation of bone cells to protein restriction, 6-month
      old female rats were pair-fed with isocaloric 15% (control) or 2.5% casein diets
      for 14 days. Animals were then treated daily with rhIGF-I/IGFBP-3 (1:4, 2.5 mg
      IGF-I/kg BW) or with vehicle for 10 days. After double-labeling, proximal
      metaphysis and mid-diaphysis of the tibia were analyzed histomorphometrically.
      Plasma osteocalcin, IGF-I, and urinary deoxypyridinoline were quantified. After
      14 days of protein restriction, significant drops in plasma osteocalcin (13%) and
      IGF-I (37%), in periosteal formation (83%) and mineral apposition (49%) rates are
      observed, indicating a decreased osteoblast recruitment and activity. In
      cancellous bone, a significant decrease in active eroded surfaces (27%) and
      osteoclast number (24%) indicates a transient depression of resorption. In rats
      fed the 15% casein diet, rhIGF-I/IGFBP-3 increases cancellous (42%) and
      periosteal (600%) formation rates, indicating an increased osteoblast
      recruitment. In protein-restricted rats, rhIGF-I/IGFBP-3 fails to increase
      cancellous or periosteal bone formation and plasma osteocalcin is significantly
      lower than in 15% casein+rhIGF-I/ IGFBP-3 rats. Protein restriction induces
      osteoblast resistance to rhIGF-I/IGFBP-3 in both bone envelopes. Low plasma IGF-I
      and osteoblast resistance to IGF-I, may contribute to the impaired periosteal
      formation.

PMID- 10965886
TI  - Stimulation of insulin-like growth factor binding protein-1 synthesis by
      interleukin-1beta: requirement of the mitogen-activated protein kinase pathway.
AB  - Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma
      protein that binds to IGF-I and IGF-II with high affinity. IGFBP-1 is elevated in
      the blood as a result of sepsis, AIDS, excessive alcohol consumption, and
      diabetes and may, in part, be responsible for the wasting observed during these
      pathophysiological conditions. The liver is the principal site of IGFBP-1
      synthesis, and we have previously shown that proinflammatory cytokines can
      directly stimulate IGFBP-1 secretion in a human hepatoma cell line (HepG2). The
      purpose of the present study was to investigate the role of the MAP kinase
      pathway in regulating IGFBP-1 synthesis by IL-1beta. We show that IL-1beta
      stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent
      manner. In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK
      1 are also phosphorylated in response to IL-1beta. The transcription factor CREB,
      a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated
      in response to IL-1beta and cAMP in HepG2 cells. The ability of IL-1beta to
      stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases
      was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated
      IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect. Conversely, a PKA
      inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate
      IGFBP-1 synthesis. The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA
      (mRNA) accumulation was additive. IL-1beta, cAMP, PD98059, and H-89 had similar
      effects on the accumulation of IGFBP-1 protein and mRNA. IL-1beta and cAMP did
      not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP
      kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of
      RSK-1 in response to IL-1beta. Our data demonstrate that the MAP kinase signal
      transduction pathway plays an important role in the regulation of IGFBP-1
      synthesis by IL-1beta.

PMID- 10965887
TI  - Establishment and characterization of a human adrenocortical carcinoma xenograft
      model.
AB  - Adrenocortical carcinomas are rare malignant tumors. They have a poor prognosis,
      as they are often diagnosed late and are usually resistant to chemotherapy. The
      lack of a suitable animal model for these tumors has been a major obstacle to the
      evaluation of new therapeutic agents. The aim of this study was to establish and
      characterize xenografts of the human adrenocortical carcinoma NCI H295R cell line
      as a model of adrenocortical carcinoma for future therapeutic trials. This cell
      line was sc injected (6 x 10(6) cells) into nude mice (n = 20). Solid tumors were
      locally measurable after 45 days at 90% of the inoculation sites. The xenografts
      were similar histologically to the original adrenocortical carcinoma from which
      the cell line was derived. The xenografts precisely reproduced the dysregulation
      of the insulin-like growth factor (IGF) system [overexpression of the IGF-II and
      IGF-binding protein-2 (IGFBP-2) genes] typical of adrenocortical carcinoma.
      Similarly to adrenocortical carcinomas, human IGFBP-2 (but not IGF-II) was
      secreted in mouse plasma. We analyzed steroid production (cortisol, 17
      hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, delta4
      androstenedione, 11-deoxycortisol, corticosterone, and testosterone). Xenografts
      produced all three class of steroids, with the preferential production of
      androgens of the delta4 pathway. The H295R xenograft model is a good model of
      human adrenocortical carcinoma, as it mimics dysregulation of the IGF system
      usually found in these tumors. It also produces IGFBP-2 and steroids that can be
      used as tumor markers. This model may therefore be useful for evaluating
      therapeutic agents.

PMID- 10965888
TI  - Androgen receptor expression in prostate carcinoma cells suppresses alpha6beta4
      integrin-mediated invasive phenotype.
AB  - Prostate cancer cells may lose androgen-sensitivity after androgen ablation
      therapy, becoming highly invasive and metastatic. The biological mechanisms
      responsible for higher tumurogenicity of androgen-independent prostate carcinomas
      are not entirely known. We demonstrate that androgen receptor regulation of
      adhesion and invasion of prostate cancer cells through modulation of alpha6beta4
      integrin expression may be one of the molecular mechanisms responsible of this
      phenomenon. We found that protein and gene expressions of alpha6 and beta4
      subunits were strongly reduced in the androgen-sensitive cell line LNCaP respect
      to the androgen-independent PC3 and that transfection of PC3 cells with a full
      length androgen receptor expression vector resulted in a decreased expression of
      alpha6beta4 integrin, reduced adhesion on laminin, and suppressed Matrigel
      invasion. Growth in soft agar was also suppressed in androgen receptor-positive
      PC3 clones. Treatment of androgen receptor positive clones with the synthetic
      androgen R1881 further reduced alpha6 and beta4 messenger RNA expression as well
      as adhesion on laminin and Matrigel invasion. Our results indicate that androgens
      regulate cell-extracellular matrix adhesion and invasion by modulation of
      integrin expression and function, thus keeping a low invasive phenotype of
      prostate cancer cells.

PMID- 10965889
TI  - Analysis of human follistatin structure: identification of two discontinuous N
      terminal sequences coding for activin A binding and structural consequences of
      activin binding to native proteins.
AB  - A primary physiological function of follistatin is the binding and neutralization
      of activin, a transforming growth factor-beta family growth factor, and loss of
      function mutations are lethal. Despite the critical biological importance of
      follistatin's neutralization of activin, the structural basis of activin's
      binding to follistatin is poorly understood. The purposes of these studies were
      1) to identify the primary sequence(s) within the N-terminal domain of the
      follistatin coding for activin binding, and 2) to determine whether activin
      binding to the native protein causes changes in other structural domains of
      follistatin. Synthetic peptide mimotopes identified within a 63-residue N
      terminal domain two discontinuous sequences capable of binding labeled activin A.
      The first is located in a region (amino acids 3-26) of follistatin, a site
      previously identified by directed mutagenesis as important for activin binding.
      The second epitope, predicted to be located between amino acids 46 and 59, is
      newly identified. Although the sequences 3-26 and 46-59 code for activin binding,
      native follistatin only binds activin if disulfide bonding is intact.
      Furthermore, pyridylethylation of Cys residues followed by N-terminal sequencing
      and amino acid analysis revealed that all of the Cys residues in follistatin are
      involved in disulfide bonds and lack reactive free sulfhydryl groups. Specific
      ligands were used to probe the structural effects of activin binding on the other
      domains of the full-length molecule, comprised largely of the three 10-Cys
      follistatin module domains. No effects on ligand binding to follistatin-like
      module I or II were observed after the binding of activin A to native protein. In
      contrast, activin binding diminished recognition of domain III and enhanced that
      of the C domain by their respective monoclonal antibody probes, indicating an
      alteration of the antigenic structures of these regions. Thus, subsequent to
      activin binding, interactions are likely to occur between regions of follistatin
      located in different domains and separated by considerable lengths of linear
      sequence. Such interactions could have important functional significance with
      respect to the structural heterogeneity of naturally occurring follistatins.

PMID- 10965890
TI  - Androgen-regulated expression of a novel member of the aldo-keto reductase
      superfamily in regrowing rat prostate.
AB  - The rat prostate is dependent on androgen for normal growth and differentiation.
      In addition, the organ undergoes rapid cell death upon withdrawal of androgen on
      castration, and the atrophied tissue is capable of regrowth after androgen
      replacement in adult animals. In our search for novel factor(s) that participate
      in this androgen-induced proliferation of adult rat prostate cells, we have
      generated a complementary DNA (cDNA) library enriched in cDNAs transiently up
      regulated after androgen stimulation in castrated rat ventral prostate using a
      PCR-based subtractive hybridization technique. Sequence analysis of about one
      hundred clones in the library showed that approximately 70% of them are identical
      or closely related to genes of known function, the remaining ones showing no or
      very low similarity to any genes characterized previously. Among the former a new
      member of the rat aldo-keto reductase superfamily that is closely related to
      aflatoxin, B1 aldehyde reductase has been identified. The newly identified
      protein (androgen-inducible aldehyde reductase, AIAR) and rat aflatoxin B1
      aldehyde reductase (AFAR) exhibit 80% amino acid sequence homology. The enzymatic
      activity toward 4-nitrobenzaldehyde of recombinant AIAR expressed in Escherichia
      coli was about 16% of that of rat AFAR. Northern blot analysis revealed AIAR
      expression in various adult rat tissues in addition to the ventral and
      dorsolateral prostates, which differs from the highly restricted expression of
      AFAR in the kidney and liver. The AIAR messenger RNA (mRNA) content of the
      ventral prostate was low in normal and castrated rats, transiently increased
      after androgen administration to castrated rats, attaining a peak 12-24 h after
      the treatment. Although the physiological substrate(s) of AIAR has not been
      identified, the current results suggest that AIAR expression is associated with
      some growth-related processes in regrowing rat prostate.

PMID- 10965891
TI  - Secretion of a lactone-hydrogenated ouabain-like effector of sodium, potassium
      adenosine triphosphatase activity by adrenal cells.
AB  - Ouabain-like factor (OLF), a mammalian cardenolide, is a counterpart to plant
      derived ouabain and is found in the adrenal, hypothalamus, and blood of several
      mammalian species. We now report the existence of a mammalian lactone
      hydrogenated ouabain-like factor (dihydro-OLF) in secretions from cultured mouse
      adrenal Y-1 cells. Dihydro-OLF structurally and functionally mimics plant-derived
      dihydroouabain. We measured both OLF and the newly discovered dihydro-OLF using
      five independent techniques: immunoreactivity with two specific antisera, one
      against ouabain and one against dihydroouabain; chromatographic mobility;
      spectral absorbance characteristics; and concentration-dependent inhibition and
      phosphorylation of Na,K-adenosine triphosphatase. All measured physical
      attributes of dihydro-OLF mimic those of plant-derived dihydroouabain, including
      a spectral shift maxima, 220 nm (OLF) to 196 nm (dihydro-OLF), with appropriately
      decreased molar absorptivity. Dihydro-OLF (IC50 = 590 nM) is a 10-fold less
      potent Na+,K+-adenosine triphosphatase inhibitor than its oxidized mammalian
      counterpart OLF (IC50 = 60 nM), just as dihydroouabain is less potent than
      ouabain. Dihydro-OLF is also 3-fold more potent than a recently identified isomer
      of plant-derived dihydroouabain (IC50 = 1,700 nM). Using antiouabain and
      antidihydroouabain antisera we estimate that 3 x 10(7) mouse adrenal Y-1 cells
      secreted 1.3 ng OLF and 8.9 ng dihydro-OLF. The relative abundance of dihydro-OLF
      is consistently greater than that of its oxidized form, OLF, in bovine adrenals
      (22-fold), human serum (13-fold), and secretions from cultured mouse Y-1 cells (5
      fold). The discoveries of OLF, OLF-genin, and now dihydro-OLF constitute an
      intriguing structural polymorphism probably involved in the synthesis,
      regulation, and metabolic control of these new hormone-like compounds.

PMID- 10965892
TI  - Expression of GC-C, a receptor-guanylate cyclase, and its endogenous ligands
      uroguanylin and guanylin along the rostrocaudal axis of the intestine.
AB  - Members of the receptor-guanylate cyclase (rGC) family possess an intracellular
      catalytic domain that is regulated by an extracellular receptor domain. GC-C, an
      intestinally expressed rGC, was initially cloned by homology as an orphan
      receptor. The search for its ligands has yielded three candidates: STa (a
      bacterial toxin that causes traveler's diarrhea) and the endogenous peptides
      uroguanylin and guanylin. Here, by performing Northern and Western blots, and by
      measuring [125I]STa binding and STa-dependent elevation of cGMP levels, we
      investigate whether the distribution of GC-C matches that of its endogenous
      ligands in the rat intestine. We establish that 1) uroguanylin is essentially
      restricted to small bowel; 2) guanylin is very low in proximal small bowel,
      increasing to prominent levels in distal small bowel and throughout colon; 3) GC
      C messenger RNA and STa-binding sites are uniformly expressed throughout the
      intestine; and 4) GC-C-mediated cGMP synthesis peaks at the proximal and distal
      extremes of the intestine (duodenum and colon), but is nearly absent in the
      middle (ileum). These observations suggest that GC-C's activity may be
      posttranslationally regulated, demonstrate that the distribution of GC-C is
      appropriate to mediate the actions of both uroguanylin and guanylin, and help to
      refine current hypotheses about the physiological role(s) of these peptides.

PMID- 10965893
TI  - Vitamin D-mediated gene regulation in phenotypically defined human B cell
      subpopulations.
AB  - Isolation of distinct subpopulations of density-fractionated normal human B
      lymphocytes reveals that the requirements for up-regulation of the vitamin D
      receptor (VDR) and initiation of 1alpha,25-dihydroxyvitamin D3 [1alpha,25
      (OH)2D3]-mediated genomic trans-activation are dependent upon the state of
      cellular activation. The kinetics of the response differ widely among these B
      cell subpopulations. However, these density-fractionated B cell subpopulations
      are phenotypically diverse and therefore are not representative of distinct
      stages of B cell maturation and differentiation. To examine the role of B cell
      differentiation on the induction and maintenance of biological receptivity to
      1,25-(OH)2D3, we purified naive, germinal center, and memory B cells based on
      their expression of CD38 and CD44 surface antigens and surface Ig isotype. These
      phenotypically defined B cell subpopulations were all found to constitutively
      express VDR, and all exhibited similar activation requirements and kinetics for
      initiation of 1,25(OH)2D3-mediated genomic trans-activation. Taken together,
      these results suggest that defined stages of differentiation in normal B cells
      are not significant predicators of VDR expression or receptivity to 1,25-(OH)2D3.
      Rather, the degree of cellular activation, regardless of maturation stage,
      determines whether the effects of this immunoregulatory hormone will influence a
      mature B lymphocyte.

PMID- 10965894
TI  - Deoxyribonucleic acid hypomethylation of male germ cells by mitotic and meiotic
      exposure to 5-azacytidine is associated with altered testicular histology.
AB  - Genomic methylation patterns originate during gametogenesis and are postulated to
      be involved in important developmental events, including gene regulation,
      embryogenesis, and genomic imprinting. In previous work, treatment of male rats
      with 5-azacytidine, a drug that blocks DNA methylation, resulted in abnormal
      embryo development when germ cells were exposed throughout spermatogenesis,
      encompassing mitotic, meiotic, and postmeiotic development, but not if they were
      only exposed postmeiotically. To explore the mechanisms underlying the effects of
      5-azacytidine on sperm function, we determined the effects of the drug on
      testicular morphology, assessed whether exposure of meiotic spermatocytes
      resulted in abnormal pregnancy outcome, and examined the role of germ cell
      genomic demethylation in mediating the effects of 5-azacytidine on spermatogonia
      and spermatocytes. Male Sprague Dawley rats were treated three times a week with
      saline or 5-azacytidine (2.5 and 4.0 mg/kg) for 6 weeks (meiotic and postmeiotic
      germ cell exposure) and 11 weeks (mitotic, meiotic, and postmeiotic exposure).
      Six weeks of paternal treatment with the highest dose of 5-azacytidine resulted
      in an increase in preimplantation loss (corpora lutea minus implantation sites)
      without affecting testicular morphology or altering sperm DNA methylation levels.
      Eleven weeks of 5-azacytidine treatment at doses that cause preimplantation loss
      resulted in severe abnormalities of the seminiferous tubules, such as
      degeneration and loss of germ cells, atrophy of seminiferous tubules, presence of
      multinuclear giant cells, and sloughing of immature germ cells into the lumen,
      and a 22-29% decrease in genomic methylation levels in epididymal sperm. On
      closer evaluation of testicular histology using terminal deoxynucleotidyl
      transferase-mediated deoxy-UTP nick end-labeling detection in situ, both 6 and 11
      weeks of 5-azacytidine treatment resulted in an increase over the control value
      in the number of apoptotic germ cells in the seminiferous tubules. Analysis of
      DNA methylation levels in isolated germ cells of treated males indicated that
      spermatogonia were more susceptible to the hypomethylating effects of 5
      azacytidine than were spermatocytes. These studies provide evidence of an
      association between demethylation of germ cell DNA and alterations in testicular
      histology.

PMID- 10965895
TI  - Plasma growth hormone pulse activation of hepatic JAK-STAT5 signaling:
      developmental regulation and role in male-specific liver gene expression.
AB  - The intracellular signaling molecule STAT5 is activated in rat liver by the
      intermittent male plasma GH pattern to a 10-fold higher level than by the more
      continuous pattern of plasma GH stimulation seen in females. Individual adult
      male rats are presently shown to exhibit large differences in liver STAT5 DNA
      binding activity, which correlates with the presence of significant levels of GH
      in plasma at the time of liver excision. Examination of STAT5 activity as a
      function of postnatal development revealed that these intermittent pulses of
      liver STAT5 activity are first observed at 5 weeks of age, when plasma GH
      pulsation first begins and expression of male-specific, GH pulse-activated liver
      genes, including CYP2C11, first occurs. Prepubertal rats exhibited low liver
      STAT5 activity, likely a consequence of the absence of high plasma GH pulses in
      these animals. Proteins required for GH activation of STAT5 are expressed in
      liver before puberty, and correspondingly, STAT5 can be precociously activated by
      exogenous administration of GH pulses given to 2-week-old rats, albeit with a
      lower sensitivity to GH than is seen in hypophysectomized adult rats. However,
      this precocious activation of STAT5, via twice daily administration of GH for 7
      days, did not lead to CYP2C11 expression or masculinization of hepatic enzyme
      profiles, unlike in GH pulse-stimulated hypophysectomized adult rats. Based on
      these findings we conclude: 1) liver STAT5 is repeatedly activated in adult male
      rats in direct response to the intermittent pattern of plasma GH stimulation; 2)
      the developmental onset of this STAT5 activation pattern supports the proposed
      requirement of STAT5 transcriptional activity for male-specific, GH pulse
      regulated hepatic gene expression; and 3) the activation of STAT5 is, by itself,
      not sufficient to impart the adult male pattern of liver gene expression,
      suggesting a requirement for additional liver factors that are absent in
      prepubertal rats.

PMID- 10965896
TI  - Interactions between the prohormone convertase 2 promoter and the thyroid hormone
      receptor.
AB  - The majority of prohormones are cleaved at paired basic residues to generate
      bioactive hormones by prohormone convertases (PCs). As PC1 and PC2, two
      neuroendocrine-specific PCs, appear to be the key enzymes capable of processing a
      variety of prohormones, alterations of PC2 and/or PC1 levels will probably have a
      profound effect on hormonal homeostasis. We investigated the regulation of PC2
      messenger RNA (mRNA) by thyroid hormone using GH3 cells to demonstrate that T3
      negatively regulated PC2 mRNA levels in a dose- and time-dependent fashion.
      Functional analysis of progressive 5'-deletions of the human (h) PC2 promoter
      luciferase constructs in GH3 cells demonstrated that the regulation probably
      occurs at the transcriptional level, and that putative negative thyroid hormone
      response elements were located within the region from -44 to + 137 bp relative to
      the transcriptional start site. Transient transfections in JEG-3 cells and COS-1
      cells showed that the suppressive effect of T3 was equally mediated by the
      thyroid hormone receptor (TR) isoforms TRalpha1 and TRbeta1. Electrophoretic
      mobility shift assays using purified TRal and retinoid X receptor-beta protein as
      well as GH3 nuclear extracts showed that regions from +51 to +71 bp and from +118
      to +137 bp of the hPC2 promoter bind to TRalpha1 as both a monomer and a
      homodimer and with TRalpha1/retinoid X receptor-beta as a heterodimer. Finally,
      the in vivo regulation of pituitary PC2 mRNA by thyroid status was demonstrated
      in rats. These results demonstrate that T3 negatively regulates PC2 expression at
      the transcriptional level and that functional negative thyroid hormone response
      elements exist in the hPC2 promoter. We postulate that the alterations of PC2
      activity may mediate some of the pathophysiological consequences of hypo- or
      hyperthyroidism.

PMID- 10965897
TI  - Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in
      the brain parenchyma: study in a transthyretin-null mouse model.
AB  - Transthyretin (TTR) is the major T4-binding protein in rodents. Using a TTR-null
      mouse model we asked the following questions. 1) Do other T4 binding moieties
      replace TTR in the cerebrospinal fluid (CSF)? 2) Are the low whole brain total T4
      levels found in this mouse model associated with hypothyroidism, e.g. increased
      5'-deiodinase type 2 (D2) activity and RC3-neurogranin messenger RNA levels? 3)
      Which brain regions account for the decreased total whole brain T4 levels? 4) Are
      there changes in T3 levels in the brain? Our results show the following. 1) No
      other T4-binding protein replaces TTR in the CSF of the TTR-null mice. 2) D2
      activity is normal in the cortex, cerebellum, and hippocampus, and total brain
      RC3-neurogranin messenger RNA levels are not altered. 3) T4 levels measured in
      the cortex, cerebellum, and hippocampus are normal. However T4 and T3 levels in
      the choroid plexus are only 14% and 48% of the normal values, respectively. 4) T3
      levels are normal in the brain parenchyma. The data presented here suggest that
      TTR influences thyroid hormone levels in the choroid plexus, but not in the
      brain. Interference with the blood-choroid-plexus-CSF-TTR-mediated route of T4
      entry into the brain caused by the absence of TTR does not produce measurable
      features of hypothyroidism. It thus appears that TTR is not required for T4 entry
      or for maintenance of the euthyroid state in the mouse brain.

PMID- 10965898
TI  - Changes in hypothalamic gene expression associated with the arrest of pulsatile
      gonadotropin-releasing hormone release during infancy in the agonadal male rhesus
      monkey (Macaca mulatta).
AB  - This study examined whether changes in the levels of the messenger RNAs (mRNAs)
      encoding the gamma-aminobutyric acid (GABA) synthesizing enzymes, glutamate
      decarboxylase (GAD)65 and GAD67 and transforming growth factor-alpha (TGFalpha)
      in the hypothalamus are correlated with the arrest of pulsatile GnRH release
      during infancy in the agonadal male monkey. This experiment also provided the
      opportunity to examine changes in hypothalamic GnRH gene expression during this
      critical phase of primate development. Male rhesus monkeys were castrated at 1
      week of age: four were killed 4-7 weeks after orchidectomy while pulsatile GnRH
      release was robust as reflected by high circulating LH levels, and four were
      killed at 12-15 months of age after establishing that pulsatile GnRH release had
      been arrested. GAD65, GAD67, TGFalpha, and GnRH mRNA levels were estimated using
      RNase protection assays employing homologous probes and the results were
      expressed relative to cyclophilin mRNA levels. GnRH peptide was measured by RIA.
      GAD65 and GAD67 mRNA levels in the hypothalamus of juveniles were significantly
      greater than those in neonatal monkeys. On the other hand, hypothalamic TGFalpha
      and GnRH mRNA (and peptide) levels in agonadal neonate and juvenile monkeys were
      indistinguishable. These results indicate that the molecular concomitants
      associated with bringing the hypothalamic GnRH pulse generator into check in
      agonadal neonatal males are not a mirror image of those previously reported at
      the time this neuronal network is reactivated at puberty when TGFalpha and GnRH
      gene expression increase and GAD65 and GAD67 mRNA levels remain unchanged. Thus,
      the neurobiological mechanism that reactivates pulsatile GnRH release at puberty
      is likely to involve more than a simple reversal of that underlying inhibition of
      the same network in late infancy.

PMID- 10965899
TI  - Identification of an osteogenic protein-1 (bone morphogenetic protein-7)
      responsive element in the promoter of the rat insulin-like growth factor-binding
      protein-5 gene.
AB  - Osteogenic protein-1 (OP-1), a member of the bone morphogenetic protein subfamily
      of the transforming growth factor-beta superfamily, induces new bone formation in
      vivo and regulates the expression of numerous growth factors. We previously
      showed that OP-1 down-regulates the transcription of the insulin-like growth
      factor-binding protein-5 (IGFBP-5) in primary cultures of fetal rat calvaria
      (FRC) cells. In the present study we identified, within the IGFBP-5 promoter, a
      21-bp region that confers OP-1 responsiveness in FRC cells. Within this region
      lie three putative cis-acting regulatory elements, viz. a CAAT-like sequence, a
      CCAAT/enhancer-binding protein (C/EBPalpha)-like element, and a c-Myb or E-box
      like motif. Mutations in the CAAT-like sequence reduced the promoter activity in
      both control and OP-1-treated cells, but did not abrogate the OP-1-induced down
      regulation. Mutations in the C/EBPalpha-like element reduced the promoter
      activity in both control and OP-1-treated cells without significantly affecting
      the extent of down-regulation. Mutations in the putative c-Myb or E-box-like
      motif reduced the promoter activity in both the OP-1-treated and control cells
      and completely abolished the inhibitory effect of OP-1 on the IGFBP-5 promoter
      activity. Gel mobility shift analyses further showed specific interaction between
      nuclear protein(s) in FRC cells and the 21-bp region. OP-1 down-regulates the
      nuclear regulatory protein interaction with the 21-bp region by reducing either
      the cellular concentration of the regulatory protein(s) or the affinity of the
      regulatory protein(s) for the OP-1 responsive element. In conclusion, we
      identified an OP-1 response region in the rat IGFBP-5 promoter and further showed
      that OP-1 down-regulates the nuclear protein interaction with the response
      element(s).

PMID- 10965900
TI  - A link between insulin resistance and hyperinsulinemia: inhibitors of
      phosphatidylinositol 3-kinase augment glucose-induced insulin secretion from
      islets of lean, but not obese, rats.
AB  - Wortmannin (5-100 nM), a specific phosphatidyinositol 3-kinase inhibitor,
      augmented 8 mM glucose-induced insulin secretion from control Sprague Dawley rat
      islets in a dose-dependent manner. This effect persisted after its removal from
      the perifusion medium; however, this augmenting effect was reduced by the calcium
      channel inhibitor nitrendipine or by lowering the glucose level to 3 mM.
      Wortmannin amplified insulin release induced by the combination of 6-8 mM glucose
      plus 1 microM carbachol; however, it had no effect on phorbol ester- or alpha
      ketoisocaproate-induced insulin secretion. The potentiating action of wortmannin
      on 8 mM glucose-induced release was duplicated by LY294002. Wortmannin had no
      effect on glucose usage rates or inositol phosphate accumulation in [3H]inositol
      prelabeled islets. Of particular significance, although 50 nM wortmannin
      potentiated 8 mM glucose-induced secretion from islets of lean Zucker control
      rats, the fungal metabolite had little effect on 8 mM glucose-induced release
      from islets of insulin-resistant Zucker fatty rats. These findings support the
      concept that the same biochemical process, inhibition ofphosphatidyinositol 3
      kinase, that causes peripheral tissue insulin resistance enhances beta-cell
      sensitivity to glucose and produces a compensatory increase in insulin secretion
      from these cells. The efficacy of wortmannin depends on the in vivo status of the
      donor's insulin signaling pathways. This elegant biochemical control mechanism in
      beta-cells ensures the maintenance of glucose homeostasis despite a reduction in
      insulin action on peripheral tissues.

PMID- 10965901
TI  - Androstenedione treatment of pregnant baboons at 0.7-0.8 of gestation promotes a
      premature forward shift in the nocturnal maternal plasma estradiol surge relative
      to progesterone and increases myometrial contraction activity.
AB  - Androstenedione treatment of pregnant monkeys at 0.8 of gestation reproduces
      endocrine, biophysical, and biochemical changes similar to those measured during
      spontaneous, term labor in the pregnant monkey. In the pregnant baboon, the
      spontaneous onset of labor at term has been attributed to a forward shift in the
      nocturnal estradiol surge relative to that of progesterone in maternal plasma.
      This study investigated whether androstenedione treatment of the pregnant baboon
      at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal surge
      of maternal plasma estradiol relative to progesterone and whether this shift is
      associated with premature increases in nocturnal myometrial activity. Eight
      pregnant baboons were prepared surgically under general anesthesia with vascular
      catheters and myometrial electromyogram electrodes between 121 and 139 days of
      gestation (term is ca. 185 days). Catheters were maintained patent by continuous
      infusion of heparinized saline from the time of surgery until one of two
      treatments began following at least 9 days of postoperative recovery. In four
      baboons (Group I), the saline administration was replaced by a continuous
      infusion of 10% intralipid vehicle during Day 1 of the experimental protocol.
      During Day 2 and Day 3, the intralipid infusion was switched for a continuous
      infusion of androstenedione dissolved in intralipid set at a low (0.8 mg x kg(-1)
      x h(-1)) and at a high (1.6 mg x kg(-1) x h(-1)) dose, each delivered for 24 h.
      The other four pregnant baboons (Group II) received 10% intralipid vehicle for
      Days 1, 2, and 3 of the experimental protocol. One baboon from Group I received
      an additional dose of 0.4 mg x kg(-1) x h(-1) for 24 h before the low and the
      high dose of androstenedione. In each baboon, during each experimental day,
      maternal arterial blood samples (1 ml) were taken at 1 h intervals for 12 h,
      starting 3 h before the onset of darkness in the animal's environment, for
      measurement of maternal plasma estradiol and progesterone concentrations via RIA.
      Myometrial contractions were counted during each night-time period of the
      experimental protocol. All pregnant baboons demonstrated increases in maternal
      plasma estradiol and progesterone concentrations at night-time. Androstenedione
      had a dose-dependent effect in elevating day-time maternal plasma estradiol
      concentrations and in promoting a forward shift in the nocturnal surge of
      maternal plasma estradiol without affecting the nocturnal progesterone profile in
      maternal plasma. Maternal treatment with androstenedione also led to an increase
      in nocturnal myometrial contraction activity. We conclude that androstenedione
      treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature
      forward shift in the nocturnal estradiol surge relative to that of progesterone
      in maternal plasma and that this shift is associated with an increase in
      nocturnal myometrial contraction activity, in a similar way to that measured
      during spontaneous onset of labor at term in this species.

PMID- 10965902
TI  - Preclinical comparison in AR4-2J tumor-bearing mice of four radiolabeled 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid-somatostatin analogs for tumor
      diagnosis and internal radiotherapy.
AB  - Somatostatin analogs labeled with radionuclides are of considerable interest in
      nuclear oncology as diagnostic or therapeutic tools for somatostatin receptor
      (SSTR)-expressing tumors. We investigated the suitability of DOTA (1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid) as a replacement for the widely
      used diethylenetriaminepentaacetic acid, to enable stable labeling of
      somatostatin analogs with both therapeutic (90Y) and diagnostic (111In)
      radionuclides. The three clinically relevant somatostatin agonists, octreotide,
      vapreotide, and lanreotide, together with the newly designed Tyr3-octreotide
      (TyrOc), were conjugated to DOTA and labeled with 90Y or 111In. For all DOTA
      somatostatin analogs tested, irrespective of the incorporated radionuclide, we
      observed favorable biodistribution profiles in AR4-2J tumor-bearing mice: 1) a
      rapid clearance from all SSTR-negative tissues except kidney; 2) a specific
      uptake in SSTR-positive tissues, including tumor; and 3) an excellent tumor
      penetration. The main route of excretion was via the kidneys. Nevertheless,
      DOTATOC was clearly superior to the other DOTA-somatostatin analogs tested, as
      well as OctreoScan, as indicated by the highest tumor-to-nontarget-tissue ratio,
      including the tumor-to-SSTR-positive-tissue ratios. The presence of different
      SSTR subtypes in the SSTR-positive tissues possibly contributes to these
      differential uptakes. We assume that the very favorable behavior of DOTATOC in
      our mouse model makes this radioligand very promising for future applications in
      nuclear oncology.

PMID- 10965903
TI  - Antidiabetic sulfonylurea enhances secretagogue-induced adrenocorticotropin
      secretion and proopiomelanocortin gene expression in vitro.
AB  - The presence of high-affinity binding sites for antidiabetic sulfonylureas (SUs)
      and the expression of SU receptor (SUR) messenger RNA in the adenohypophyseal
      cells have recently been reported. In this study, we examined the effects of SU
      on POMC gene expression and ACTH secretion using the AtT20PL cell line, a
      subclone of AtT20 in which the rat POMC 5'-promoter-luciferase fusion gene was
      stably incorporated. A representative SU glibenclamide inhibited the basal POMC
      5'-promoter activity. In contrast, glibenclamide enhanced forskolin- or CRH
      induced POMC expression in a dose-dependent manner. Interestingly, the latter
      effect was not observed under treatment with 3-isobutyl-1-methylxanthine, a
      nonselective phosphodiesterase inhibitor. Furthermore, diazoxide, an opener of
      the ATP-sensitive K+ channel, only antagonized the suppressive effect of
      glibenclamide. Lastly, RT-PCR analysis showed that mouse SUR (but not SUR2)
      messenger RNA was expressed in this cell line. These results suggest that, in
      AtT20PL cells, SU has dual effects, i.e. a suppressive effect on basal POMC
      expression through diazoxide-sensitive (ATP-sensitive) K+-channel-mediated
      mechanism, and an enhancing effect on cAMP/protein kinase A-stimulated POMC
      expression through a different mechanism (probably mediated by
      phosphodiesterase). To our knowledge, this is the first report showing the effect
      of SU on the expression of the anterior pituitary hormone gene.

PMID- 10965904
TI  - Regulation of hypothalamic neuropeptide Y Y1 receptor gene expression during the
      estrous cycle: role of progesterone receptors.
AB  - Neuropeptide Y (NPY) stimulates the release of GnRH in an estrogen (E2)-dependent
      manner, which is important in generating preovulatory GnRH surges. We tested the
      hypothesis that E2 up-regulates NPY's actions by stimulating NPY Y1 receptor
      (Y1r) gene expression through a mechanism mediated by E2's ability to induce
      progesterone (P) receptors (PRs). In initial experiments, a specific Y1r
      antagonist BIBP3226 was used to confirm the involvement of Y1r in the stimulatory
      effects of NPY on in vivo GnRH release. Hypothalamic Y1r messenger RNA (mRNA)
      levels were then measured using competitive RT-PCR and were found to be
      significantly increased at 1000, 1200, and 1400 h on proestrus compared with
      other times of the day or cycle stage. Ovariectomy eliminated these increases,
      and E2 treatment restored them. Additional P treatment produced even larger
      increases in Y1r mRNA levels. To assess the role of PRs in stimulating Y1r
      expression, proestrous rats were treated with PR antagonist or oil vehicle and
      killed at 1200 h. Treatment with PR antagonist completely blocked the proestrous
      rise in Y1r gene expression. In parallel experiments, the same in vivo PR
      antagonist treatments also blocked NPY stimulation of GnRH release in vitro.
      Together our findings reveal that 1) Y1r mRNA levels are increased during the
      late morning and afternoon of proestrus; 2) Y1r mRNA levels are similarly
      increased by E2, and to an even greater extent by additional P; and 3) PR
      antagonism blocks both increased Y1r mRNA and induction of GnRH responsiveness to
      NPY. These observations support the idea that E2 up-regulates GnRH neuronal
      responses to NPY through stimulation of Y1r gene expression, and that E2's
      actions are mediated by the induction and subsequent activation of PRs.

PMID- 10965905
TI  - Insulin receptor substrate-1-mediated enhancement of growth hormone-induced
      mitogen-activated protein kinase activation.
AB  - Interaction of GH with the cell-surface GH receptor (GHR) causes activation of
      the GHR-associated tyrosine kinase, JAK2, and consequent triggering of signaling
      cascades including the STAT, Ras/Raf/MEK1/MAP kinase, and insulin receptor
      substrate-1(IRS-1)/PI3kinase pathways. We previously showed that IRS- and GHR
      deficient 32D cells that stably express the rabbit GHR and rat IRS-1 (32D-rbGHR
      IRS-1) exhibited markedly enhanced GH-induced proliferation and MAP kinase (ERK1
      and ERK2) activation compared with cells expressing only the GHR (32D-rbGHR). We
      now examine biochemical mechanism(s) by which IRS-1 augments GH-induced MAP
      kinase activation. Time-course experiments revealed a similarly transient
      (maximal at 15 min) GH-induced ERK1 and ERK2 activation in both 32D-rbGHR and 32D
      rbGHR-IRS-1 cells, but, consistent with our prior findings, substantially greater
      activation was seen in the IRS-1-containing cells. In both cells, GH-induced MAP
      kinase activation was markedly blunted by the MEK1 inhibitor, PD98059, but not by
      the PKC inhibitor, GF109203X. Interestingly, pretreatment with the PI3K
      inhibitor, wortmannin (EC50 approximately 10 nM), significantly reduced GH
      induced MAP kinase activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells. This
      same pattern in both cells of IRS-1-dependent augmentation and IRS-1-independent
      wortmannin sensitivity was also observed for GH-induced activation of Akt and
      MEK1 (using state-specific antibody blotting for both), despite the lack of
      difference in GHR, JAK2, SHP-2, p85, Akt, Ras, Raf-1, MEK1, ERK1, or ERK2
      abundance between the two cells. A different PI3K inhibitor, LY294002 (50
      microM), substantially inhibited (roughly 72%) GH-induced MAP kinase activation
      in 32D-rbGHR-IRS-1 cells, but only marginally (and statistically insignificantly)
      inhibited GH-induced MAP kinase activation in 32D-rbGHR cells. Because GH-induced
      Akt activation was completely inhibited in both cells by the same concentration
      of LY294002, these findings indicate that the wortmannin sensitivity of both the
      IRS-1-independent and -dependent GH-induced MAP kinase activation may reflect the
      activity of another wortmannin-sensitive target(s) in addition to PI3K in
      mediation of GH-induced MAP kinase activation in these cells. Notably, GH-induced
      STAT5 tyrosine phosphorylation, unlike Akt or MAPK activation, did not differ
      between the cells. Finally, while GH promoted accumulation of activated Ras in
      both cells, both basal and GH-induced activated Ras levels were greater in cells
      expressing IRS-1 than in 32D-rbGHR cells. These data indicate that while GH
      induces tyrosine phosphorylation of STAT5 and activation of the Ras/Raf/MEK1/MAPK
      and PI3K pathways, IRS-1 expression augments the latter two more than the former.

PMID- 10965906
TI  - 5-thio-D-glucose elevates renal transforming growth factor beta-1 at a dose that
      does not prevent streptozocine diabetes in rats.
AB  - Studies of early nephropathy in streptozocin (STZ)-treated rats are complicated
      by the nephrotoxicity of this agent. Inhibitors of the diabetogenic actions of
      STZ have been described, but their effects on the kidney have not been assessed.
      This study examined the effects of one agent, 5-thio-D-glucose (5TG) on renal
      hypertrophy and transforming growth factor beta1 (TGF-beta1). Forty male Sprague
      Dawley rats were divided into four groups: saline controls (SC), 5TG alone, 5TG +
      STZ, and STZ. After 2 weeks of observation, urine, plasma, and kidneys were
      studied. Nine of 10 STZ rats were diabetic at the time of euthanasia, as were 5
      of 10 5TG + STZ animals. Both tissue levels of messenger RNA and protein for
      active and total TGF-beta1 were elevated in STZ and 5TG-STZ animals compared with
      SC. 5TG also elevated mRNA and produced protein levels intermediate to the other
      groups. 5TG plus STZ is an unacceptable control for nephropathy studies in STZ
      diabetes, both because of lack of efficacy at the dose studied and the induction
      of TGF-beta1 by 5TG. 5TG may yet prove of value in studying control of renal TGF
      beta1 expression and excretion.

PMID- 10965907
TI  - Identification and characterization of a new member of the placental prolactin
      like protein-C (PLP-C) subfamily, PLP-Cbeta.
AB  - We have isolated a complementary DNA (cDNA) clone that encodes a new member of
      the PRL-like protein-C (PLP-C) subfamily of the PRL gene family. The clone was
      amplified from a 13.5-day-old mouse conceptus cDNA library by PCR using primers
      based on conserved regions of PLP-C sequences. The full-length cDNA encodes a
      predicted protein of 241 residues, which contains a putative signal sequence and
      2 putative N-linked glycosylation sites. The predicted protein shares 55-66%
      amino acid identity with mouse PLP-Calpha and rat PLP-D, PLP-H, PLP-Cv, and PLP-C
      and also contains 6 homologously positioned cysteine residues. Thus, we named
      this protein PLP-Cbeta for consistency. We have also isolated rat PLP-Cbeta from
      rat placenta cDNA library. Surprisingly, two messenger RNA (mRNA) isoforms of rat
      PLP-Cbeta were isolated: one mRNA (rPLP-Cbeta) encodes a 241-amino acid product,
      but another mRNA (rPLP-Cbetadelta39) lacks 39 bases that encode for a region rich
      in aromatic amino acids. The 39-bp region corresponds to exon 3 of other PLP-C
      subfamily members, such as PLP-Calpha, PLP-Cv, and d/tPRP. It suggests that the
      two isoforms are probably generated by an alternative splicing from a single
      gene. RT-PCR analysis revealed that the rPLP-Cbeta form was dominantly expressed
      in placenta, although both isoforms are coexpressed during placentation. The
      mouse PLP-Cbeta mRNA expression, which was specific to the placenta, was first
      detected by Northern analysis on embryonic day 11.5 (E 11.5) and persisted until
      birth. However, in situ hybridization analysis revealed mPLP-Cbeta expression on
      E 10.5 in specific trophoblast subsets, such as giant cells and
      spongiotrophoblast cells. mPLP-Cbeta mRNA was detected in the labyrinthine zone
      on E 18.5, suggesting that spongiotrophoblast cells had penetrated the
      labyrinthotrophoblast zone. Consistent with the observed expression in
      trophoblast giant cells, PLP-Cbeta expression was also detected in in vitro
      differentiated Rcho-1 cells, which express the trophoblast giant cell phenotype.
      In summary, overall high amino acid identity (79%), the locations of cysteine
      residues, and consensus sites for N-linked glycosylation between mouse and rat
      PLP-Cbeta clearly indicate that PLP-Cbeta is a bona fide member of the PLP-C
      subfamily. The conservation between mouse and rat, the presence of alternative
      isoforms, and the pattern of expression during gestation suggest the biological
      significance of PLP-Cbeta during pregnancy.

PMID- 10965908
TI  - Epoxide hydrolase affects estrogen production in the human ovary.
AB  - To investigate the mechanisms of ovarian cell differentiation, we raised a new
      monoclonal antibody, HCL-3, which reacted with human luteal cells. It also
      reacted with human and porcine hepatocytes. The immunoaffinity-purified HCL-3
      antigen from human corpora lutea (CL) was shown to be a 46-kDa protein. The N
      terminal 22 amino acids of the 46-kDa protein from porcine liver exhibited high
      homology (82%) to human microsomal epoxide hydrolase (mEH). The purified HCL-3
      antigen from human CL or porcine liver showed EH enzyme activity, confirming that
      HCL-3 antigen is identical to mEH, which is reported to detoxify the toxic
      substrates in the liver. In human follicles, mEH was immunohistochemically
      detected on granulosa and theca interna cells. In the menstrual and pregnant CL,
      mEH was also expressed on large and small luteal cells. A competitive inhibitor
      of EH, 1,2-epoxy-3,3,3-trichloropropane, inhibited the conversion of estradiol
      from testosterone by granulosa cells cultured in vitro, indicating the
      involvement of mEH in ovarian estrogen production. Because anticonvulsant sodium
      valproate and its analogues were reported to inhibit EH enzyme activity, these
      findings provide a new insight into the etiology of endocrine disorders that are
      frequently observed among epileptic patients taking anticonvulsant drugs.

PMID- 10965909
TI  - Molecular cloning of growth hormone-releasing hormone/pituitary adenylyl cyclase
      activating polypeptide in the frog Xenopus laevis: brain distribution and
      regulation after castration.
AB  - Pituitary adenylyl cyclase-activating peptide (PACAP) appears to regulate several
      neuroendocrine functions in the frog, but its messenger RNA (mRNA) structure and
      brain distribution are unknown. To understand the potential role of PACAP in the
      male frog hypothalamic-pituitary-gonadal axis, we cloned the frog Xenopus laevis
      PACAP mRNA and determined its distribution in the brain. We then analyzed the
      castration-induced alterations of mRNA expression for PACAP and its selective
      type I receptor (PAC1) in the hypothalamic anterior preoptic area, a region known
      to regulate reproductive function. The PACAP mRNA encodes a peptide precursor
      predicted to give rise to both GH-releasing hormone and PACAP. The deduced
      peptide sequence of PACAP-38 was nearly identical to that of human PACAP with one
      amino acid substitution. Abundant PACAP mRNA was detected in the brain, but not
      several other tissues, including the testis. In situ hybridization revealed
      strong expression of the PACAP gene in the dorsal pallium, ventral hypothalamus,
      and nuclei of cerebellum. PACAP mRNA signals were weak to moderate in the
      hypothalamic anterior preoptic area and were absent in the pituitary. Castration
      induced an increase in the expression of PACAP and PAC1 receptor mRNAs in the
      hypothalamic anterior preoptic area after 3 days. Replacement with testosterone
      prevented the castration-induced changes. These results provide a molecular basis
      for studying the physiological functions of PACAP in frog brain and suggest that
      PACAP may be involved in the feedback regulation of hypothalamic-pituitary
      gonadal axis.

PMID- 10965910
TI  - Photoaffinity labeling identification of a specific binding protein for the
      anabolic steroids stanozolol and danazol: an oligomeric protein regulated by age,
      pituitary hormones, and ethinyl estradiol.
AB  - We have demonstrated previously that both rat and human liver microsomes contain
      a highly specific binding protein for the anabolic steroids stanozolol (ST) and
      danazol (DA). In this study we solubilized the male rat liver ST-binding protein
      (STBP) and investigated the following parameters: 1) pharmacological properties,
      2) hydrodynamic properties, 3) peptidic composition, 4) the effects of age and
      hypophysectomy, and 5) inducibility by 17alpha-ethinyl estradiol. We found that
      STBP is an integral protein bound to the endoplasmic reticulum. 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) provided its optimal
      solubilization without changes in its pharmacological properties, i.e. high
      specificity for ST and danazol, between natural steroids and ligands of low
      affinity glucocorticoid-binding sites or of progesterone-binding sites.
      Hydrodynamic properties of the STBP showed that it has a molecular mass of at
      least 118 kDa. SDS-PAGE of covalently labeled STBP under nonreducing conditions
      showed that [3H]ST binds to a 110-kDa protein. The STBP was resolved under
      reducing conditions into three peptides of 55, 31, and 22 kDa, respectively. STBP
      increased from immature to adult rats, and it dramatically decreased after
      hypophysectomy. Unlike the 22-kDa peptide, both the 55- and 31-kDa peptides
      drastically decreased in both immature and hypophysectomized rats. 17alpha
      Ethinyl estradiol administration to immature or hypophysectomized rats induced
      the 55- and 31-kDa [3H]STBP to a greater extent than the 22-kDa peptide. Thus,
      STBP appears as an oligomeric protein composed of hormone-regulated peptides. The
      availability of solubilized STBP and the fact that it can be induced in vivo
      represent major steps toward the purification and functional significance of this
      unique steroid-binding protein.

PMID- 10965911
TI  - Improved glucose and lipid metabolism in genetically obese mice lacking aP2.
AB  - Adipocyte fatty acid-binding protein, aP2, is a member of the intracellular fatty
      acid binding protein family. Previously, studies have shown increased insulin
      sensitivity in aP2-deficient mice with dietary obesity. Here, we asked whether
      aP2-related alterations in lipolytic response and insulin production are features
      of obesity-induced insulin resistance and investigated the effects of aP2
      deficiency on glucose homeostasis and lipid metabolism in ob/ob mice, a model of
      extreme obesity. ob/ob mice homozygous for the aP2 null allele (ob/ ob-aP2-/-)
      became more obese than ob/ob mice as indicated by significantly increased body
      weight and fat pad size but unaltered body length. However, despite their extreme
      adiposity, ob/ob-aP2-/- animals were more insulin-sensitive compared with ob/ob
      controls, as demonstrated by significantly lower plasma glucose and insulin
      levels and better performance in both insulin and glucose tolerance tests. These
      animals also showed improvements in dyslipidemia and had lower plasma
      triglyceride and cholesterol levels. Lipolytic response to beta-adrenergic
      stimulation and lipolysis-associated insulin secretion was significantly reduced
      in ob/ob-aP2-/- mice. Interestingly, glucose-stimulated insulin secretion, while
      virtually abolished in ob/ob controls, was significantly improved in ob/ob-aP2-/-
      animals. There were no apparent morphological differences in the structure or
      size of the pancreatic islets between genotypes. Taken together, the data
      indicate that in obesity, aP2-deficiency not only improves peripheral insulin
      resistance but also preserves pancreatic beta cell function and has beneficial
      effects on lipid metabolism.

PMID- 10965912
TI  - Adenosine is an agonist of the growth hormone secretagogue receptor.
AB  - Growth hormone secretagogues (GHSs) are synthetic compounds that induce GH
      release in several species, including man. The aim of the current study was to
      identify hypothalamic GHS receptor (GHS-R) agonists. This led to the discovery of
      adenosine as a GHS-R agonist. We demonstrate that adenosine as well as the A1
      adenosine receptor agonist N6-R-phenylisopropyladenosine (R-PIA) induce calcium
      responses, with EC50 values of 50 nM and 0.5 nM, respectively, in cells which
      express recombinant human GHS-R. However, neither compound induces a calcium
      response in nontransfected cells. Binding experiments show that adenosine and the
      GHS compound MK-0677 bind to membranes from GHS-R expressing cells with nearly
      identical Bmax values (2.6 +/- 0.1 x 10(-10) mol/mg protein for adenosine and 2.0
      +/- 0.3 x 10(-10) mol/mg protein for MK-0677). However, no binding to membranes
      from nontransfected cells could be detected. Furthermore, we show that the IC50
      values for inhibition of the adenosine, R-PIA, and GHS induced calcium responses
      by the GHS-R antagonist [D-Arg1, D-Phe5, D-Trp7,9, D-Leu11]-substance P are
      similar. These findings strongly suggest that adenosine and R-PIA are agonists of
      the GHS-R. Interestingly, neither adenosine nor R-PIA were able to induce GH
      release from rat pituitary cells in vitro. The implications of the latter finding
      is discussed.

PMID- 10965913
TI  - The role of CBP in estrogen receptor cross-talk with nuclear factor-kappaB in
      HepG2 cells.
AB  - Functional interactions or cross-talk between ligand-activated nuclear receptors
      and the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB)
      may play a major role in ligand-mediated modification of diseases processes. In
      particular, the cardioprotective effects of estrogen replacement therapy are
      thought to be due in part to the ability of ligand-bound estrogen receptor (ER)
      to inhibit NF-kappaB function. In the current study 17beta-estradiol-bound
      ERalpha interfered with cytokine-induced activation of a NF-kappaB reporter in
      HepG2 cells. The estrogen metabolite, 17alpha-ethinyl estradiol, and the
      phytoestrogen, genistein, were also effective inhibitors of NF-kappaB activation,
      whereas tamoxifen, 4-hydroxytamoxifen, and raloxifene were inactive. This
      inhibition was reciprocal, as NF-kappaB interfered with the trans-activation
      properties of ERalpha. Ligand-bound ERalpha did not inhibit NF-kappaB binding to
      DNA, but it did decrease the histone acetyltransferase activity required for NF
      kappaB transcriptional activity. Coexpression of the transcription coactivator
      CREB binding protein (CBP), but not steroid receptor coactivator 1a, reversed the
      ERalpha-mediated inhibition of NF-kappaB activity. Mammalian two-hybrid
      experiments also revealed that ligand-bound ERalpha can interact functionally
      with CBP-NF-kappaB complexes. We suggest that CBP targeting by ERalpha results in
      the inhibition of NF-kappaB and may occur through formation of transcriptionally
      inert multimeric complexes that are dependent upon the nature of the ERalpha
      ligand.

PMID- 10965914
TI  - Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and
      lactation.
AB  - Stanniocalcin is a glycoprotein hormone that appears to play a paracine/autocrine
      role in several mammalian tissues. Recently studies have shown that stanniocalcin
      is highly expressed in the ovaries of mice and humans and we have investigated
      its expression in the mouse ovary during several physiological states to identify
      potential functional relationships. During postnatal development the pattern of
      stanniocalcin (STC) gene expression begins to become thecal-restricted as early
      as day 5 and achieves the adult pattern of expression by two weeks of age. During
      postnatal development the primary sites of STC protein localization are the theca
      and oocytes and after maturation it is also strongly concentrated in the corpora
      lutea. Over the estrous cycle the pattern of both STC gene expression and protein
      localization do not show dramatic changes though STC immunoreactivity (STCir)
      staining appears to be greatest during metestrus I. In the superovulation model,
      however, we observed a significant increase in STC messenger RNA (mRNA) levels
      after treatment with hCG implying regulation by LH. During gestation the
      expression of ovarian STC increases 15-fold and is localized to the theca
      interstitial cells with lower expression also being found in the corpora lutea.
      STC also becomes detectable in the serum for the first time suggesting an
      endocrine role for STC during gestation. Interestingly, the presence of a nursing
      litter appears to up-regulate STC gene expression in lactating mice suggesting a
      role for ovarian STC in lactation. Also striking is the intense STCir staining
      found in oocytes as they are devoid of STC mRNA, thus implying a role for STC in
      oocyte maturation. Stanniocalcin, to our knowledge, is unique because no other
      secreted proteins produced by the ovarian thecal-interstitial compartment are
      significantly induced during mouse pregnancy. In summary, our data provide
      evidence for the active regulation of STC expression in the ovary during
      gestation and lactation and therefore implies that STC is a new regulator of the
      gestational and nursing state.

PMID- 10965915
TI  - Progesterone regulation of the progesterone receptor in rat gonadotropes.
AB  - For rat pituitary cells, progesterone receptor (PR) protein localizes to
      gonadotropes and PR messenger RNA is induced by E2 and rapidly but transiently
      down-regulated by progesterone. Here we quantitatively establish the down
      regulatory effect of progesterone on PR protein and evaluate possible mechanisms.
      Nuclear PR-immunoreactivity (PR-IR) in gonadotropes, identified by dual
      immunofluorescence, was analyzed by quantitative confocal microscopy. Pituitary
      cells from female rats were cultured +/- 0.2 nM E2 for 3 days. We confirmed the
      E2 requirement for PR induction in gonadotropes and determined that the increase
      in PR-IR required about 24 h. After removal of E2, PR-IR decreases were not found
      until 24-36 h. Addition of progesterone (40 nM) to E2-treated cells led to a
      dramatic loss in PR-IR by 9 h (26% of control); by 24 h, PR-IR was barely
      detectable. Reappearance of nuclear PR-IR required progesterone removal (8-fold
      increase by 12 h after progesterone removal) and protein synthesis (cycloheximide
      inhibited the reappearance of PR-IR). Although progesterone decreased PR-IR
      whether or not E2 was present concurrent with progesterone, the recovery of PR-IR
      required E2. RU486 completely blocked progesterone-induced PR down-regulation.
      Because the sustained progesterone-induced loss of PR protein did not correlate
      with previously reported temporal changes in PR messenger RNA levels, we examined
      a role for protein degradation. When cells were coincubated with progesterone and
      the proteasome inhibitor, MG132 (1 microM), the expected decrease in PR protein
      was abrogated. In summary, progesterone leads to a rapid and extensive reduction
      in nuclear PR protein in gonadotropes. The progesterone-dependent down-regulation
      of PR occurs, at least in part, by a proteasome-mediated pathway. Recovery of PR
      protein requires removal of progesterone, the presence of E2, and protein
      synthesis. These dynamic changes in nuclear PR levels coincide with the temporal
      extent of the preovulatory LH surge in rats and could provide a basis for
      progesterone's biphasic action on LH secretion.

PMID- 10965917
TI  - Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator.
AB  - An androgen receptor (AR) interacting protein was isolated from a HeLa cell
      complementary DNA library by two-hybrid screening in yeast using the AR DNA and
      ligand binding domains [amino acids (aa) 481-919] as bait. AR binding of the
      protein in yeast was dependent on the presence of testosterone or
      dihydrotestosterone (DHT). The isolated protein is identical to thyroid receptor
      activator molecule TRAM-1 but lacking aa 1-458. TRAM-1 is a steroid receptor
      coactivator-3 (SRC-3) subtype. In affinity matrix assays, 35S-labeled TRAM-1
      bound the GST-AR ligand binding domain (aa 624-919) and GST-AR N-terminal and DNA
      binding domains (aa 1-660), but not the GST-AR DNA binding domain (aa 544-634)
      alone. Coexpression of TRAM-1 increased DHT-dependent AR transactivation 5-fold
      and constitutive activity of AR (aa 1-660) N-terminal and DNA-binding domains
      increased 9-fold. Full-length TRAM-1 (aa 1-1424) and the partial (aa 459-1424)
      were AR and GR coactivators as was SRC-1. In human testis, immunostaining of SRC
      3 colocalized with AR in nuclei of Sertoli cells and peritubular myoid cells,
      indicating it could function as an AR coactivator in these cells. SRC-3 was also
      present in nuclei of spermatogenic cells where AR was not expressed, suggesting
      it might also be a coactivator with other nuclear receptors that regulate
      spermatogenesis.

PMID- 10965916
TI  - Activation of a uterine insulin-like growth factor I signaling pathway by
      clinical and environmental estrogens: requirement of estrogen receptor-alpha.
AB  - Recent data indicate that insulin-like growth factor I (IGF-I) may have a
      function in mediating the mitogenic effects of 17beta-estradiol (E2) in the
      uterus and in regulating the growth of uterine neoplasms. This study was designed
      to determine whether synthetic and plant-derived chemicals that interact with
      estrogen receptor-alpha (ERalpha) and elicit estrogenic responses also mimic E2
      by activating the uterine IGF-I signaling pathway. Ovariectomized adult female
      mice were treated with both environmental and clinically relevant chemicals
      previously reported to display estrogenic and/or antiestrogenic properties, and
      their uteri were evaluated for an activated IGF-I signaling pathway.
      Diethylstilbestrol, 4-hydroxytamoxifen, the raloxifene analog LY353381, 2,2-bis(p
      hydroxyphenyl)-1,1,1-trichloroethane (HPTE), bisphenol A, and genistein were
      shown to mimic E2 in the uterus by increasing the level of IGF-I messenger RNA,
      inducing IGF-I receptor (IGF-IR) tyrosine phosphorylation, stimulating the
      formation of IGF-IR signaling complexes, and increasing both proliferating cell
      nuclear antigen expression and the number of mitotic cells in the epithelium. The
      dose of chemical necessary to activate IGF-I signaling varied, with the order of
      potency: E2 = diethylstilbestrol > LY353381 > 4-hydroxytamoxifen > genistein >
      HPTE > bisphenol A. Administration of the chemicals to ERalpha knockout mice did
      not activate IGF-IR, indicating that ERalpha is required for activation of
      uterine IGF-IR by these diverse chemicals. This study demonstrates that several
      chemicals shown previously to display estrogenic activities also mimic E2 by
      activating uterine IGF-I signaling.

PMID- 10965918
TI  - Regulation of the GABA(A) receptor by nitric oxide in frog pituitary
      melanotrophs.
AB  - Nitric oxide (NO) is implicated in the regulation of various endocrine functions,
      but the effect of NO on GABA(A) receptor transmission has never been reported in
      endocrine cells. In the present study, we have investigated the effects of
      various agents acting on the NO transduction pathway on GABA(A) receptor function
      in frog pituitary melanotrophs. Histochemical studies using the NADPH-diaphorase
      reaction and immunohistochemical labeling with antibodies against neuronal NO
      synthase (nNOS) revealed that nNOS is expressed in the intermediate lobe of the
      pituitary and in cultured melanotrophs. Whole-cell patch-clamp recordings showed
      that the specific substrate of NOS L-arginine (L-Arg, 10(-4) M) or the NO donor
      sodium nitroprusside (10(-5) M) provoked a long-lasting inhibition of the current
      evoked by GABA (5 x 10(-6) M). The NOS inhibitor L-nitroarginine (10(-5) M)
      produced a biphasic effect, i.e. a transient decrease followed by a delayed
      increase of the GABA-evoked current amplitude. Similarly, the specific nNOS
      inhibitor 7-nitroindazole and the specific inducible NOS (iNOS) inhibitor
      aminoguanidine (10(-5) M each) provoked a transient depression of the current
      followed by a sustained potentiation. Formation of cGMP in neurointermediate
      lobes was enhanced by L-Arg (10(-4) M) and by the calcium-releasing agent
      caffeine (10(-4) M), and inhibited by the calmodulin (CaM)/Ca2+ complex blocker
      W7 (10(-5) M). The GABA-evoked current was potentiated by the guanylyl cyclase
      inhibitor ODQ (10(-8)-10(-7) M) and inhibited by the protein kinase G (PKG)
      activator 8pCPT-cGMP (3 x 10(-7)-3 x 10(-5) M). The present data indicate that
      NO, produced by a CaM/Ca2+-dependent NOS in frog melanotrophs, exerts an
      autocrine inhibitory effect on the GABA-evoked current. The action of NO on the
      GABA(A) receptor function is mediated through activation of the cGMP/PKG pathway.

PMID- 10965919
TI  - Differentiation of granulosa cell line: follicle-stimulating hormone induces
      formation of lamellipodia and filopodia via the adenylyl cyclase/cyclic adenosine
      monophosphate signal.
AB  - FSH plays a crucial role in granulosa cell differentiation and follicular
      development during the ovulation cycle. The early events of granulosa cell
      differentiation in cell culture involve changes in the cell morphology and cell
      to-cell interactions. To determine the cause and signaling mechanism for these
      changes, we examined an undifferentiated rat ovarian granulosa cell line that
      grows in a defined serum-free medium, expresses the FSH receptor, terminally
      differentiates when exposed to FSH, and undergoes apoptosis upon FSH withdrawal.
      FSH bound the FSH receptor on rat ovarian granulosa cells, and the liganded
      receptor activated adenylyl cyclase (AC) to produce cAMP but did not mobilize
      Ca2+. In addition, we observed massive reorganization of the actin cytoskeleton
      within 3 h of FSH treatment. This involves formation of lamellipodia and
      filopodia and spreading of multilayer cell aggregates to monolayers. This actin
      reorganization and cell transformation could also be induced by the AC activator,
      forskolin, in the absence of FSH. Furthermore, AC inhibitors blocked the FSH
      dependent actin reorganization and transformation. On the other hand,
      phospholipase C inhibitors did not block the FSH-induced changes. Taken together,
      our observations indicate that the AC/cAMP signal is necessary and sufficient for
      FSH-dependent granulosa cell differentiation, including massive reorganization of
      the actin cytoskeleton and changes in the cell morphology and cell-to-cell
      interactions. There is no evidence that the phospholipase C signal and Ca2+
      mobilization are involved in this process.

PMID- 10965920
TI  - Evidence that estrogens directly alter androgen-regulated prostate development.
AB  - Neonatal exposure to high doses of estrogen results in permanent suppression of
      prostate growth and reduced sensitivity to androgens in adulthood. It is unclear
      whether alterations in prostate growth are due to a direct effect of estrogens on
      the gland or are the result of hypothalamic-pituitary-gonadal axis suppression
      and a subsequent reduction in androgen levels. Therefore, the aim of this study
      was to determine whether estrogens have a direct effect on the prostate using a
      defined method of culturing neonatal prostates. Newborn rat ventral prostates
      were microdissected and cultured in the presence of testosterone, which resulted
      in branching morphogenesis and ductal canalization. Solid cords of epithelium
      differentiated into acini lined by tall columnar epithelial cells; these acini
      were surrounded by stromal cells, expressing smooth muscle alpha-actin. When
      cultured in the presence of 17beta-estradiol or diethylstilbestrol in addition to
      testosterone, androgen-induced prostatic growth was reduced, and differentiation
      was altered. Although estrogen-treated explants were smaller than controls,
      quantification of epithelial, stromal, and luminal volumes using unbiased
      stereology revealed significant changes; the proportion of epithelial cells and
      lumen decreased, and the proportion of stroma increased compared with control
      values. Concurrent with this reduced growth rate, we observed a disturbance in
      the branching pattern and a reduction in ductal canalization. Specifically,
      stromal differentiation and organization were disrupted, so that a discontinuous
      smooth muscle layer was observed around the epithelial ducts, and epithelial
      differentiation was altered. The effects of estrogens were not accompanied by a
      decrease in androgen response via the androgen receptor, because
      immunolocalization of this receptor remained constant. These data demonstrate
      that high doses of estrogens are growth inhibitory and have direct effects on
      prostate development in vitro, which may occur in vivo in addition to indirect
      effects via suppression of the hypothalamic-pituitary-gonadal axis.

PMID- 10965921
TI  - Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast
      development and function.
AB  - Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear
      factor-kappaB ligand (RANKL)/osteoclast differentiation factor, inhibits both
      differentiation and function of osteoclasts. We previously reported that OPG
      deficient mice exhibited severe osteoporosis caused by enhanced osteoclastic bone
      resorption. In the present study, potential roles of OPG in osteoclast
      differentiation were examined using a mouse coculture system of calvarial
      osteoblasts and bone marrow cells prepared from OPG-deficient mice. In the
      absence of bone-resorbing factors, no osteoclasts were formed in cocultures of
      wild-type (+/+) or heterozygous (+/-) mouse-derived osteoblasts with bone marrow
      cells prepared from homozygous (-/-) mice. In contrast, homozygous (-/-) mouse
      derived osteoblasts strongly supported osteoclast formation in the cocultures
      with homozygous (-/-) bone marrow cells, even in the absence of bone-resorbing
      factors. Addition of OPG to the cocultures with osteoblasts and bone marrow cells
      derived from homozygous (-/-) mice completely inhibited spontaneously occurring
      osteoclast formation. Adding 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] to
      these cocultures significantly enhanced osteoclast differentiation. In addition,
      bone-resorbing activity in organ cultures of fetal long bones derived from
      homozygous (-/-) mice was markedly increased, irrespective of the presence and
      absence of bone-resorbing factors, in comparison with that from wild-type (+/+)
      mice. Osteoblasts prepared from homozygous (-/-), heterozygous (+/-), and wild
      type (+/+) mice constitutively expressed similar levels of RANKL messenger RNA,
      which were equally increased by the treatment with 1alpha,25(OH)2D3. When
      homozygous (-/-) mouse-derived osteoblasts and hemopoietic cells were cocultured,
      but direct contact between them was prevented, no osteoclasts were formed, even
      in the presence of 1alpha,25(OH)2D3 and macrophage colony-stimulating factor.
      These findings suggest that OPG produced by osteoblasts/stromal cells is a
      physiologically important regulator in osteoclast differentiation and function
      and that RANKL expressed by osteoblasts functions as a membrane-associated form.

PMID- 10965922
TI  - Accumulation of synaptosomal-associated protein of 25 kDa (SNAP-25) and other
      proteins associated with the secretory pathway in GH4C1 cells upon treatment with
      estradiol, insulin, and epidermal growth factor.
AB  - Treatment of rat pituitary GH4C1 cells with estradiol, insulin, and epidermal
      growth factor induces secretory granule accumulation, PRL storage, and
      stabilization of ICA512, a membrane protein associated with secretory granules.
      In these investigations we found that the same treatment induced accumulation
      over 2-fold of other proteins in the secretory pathway, including synaptosomal
      associated protein of 25 kDa (SNAP-25), synaptotagmin III, synaptobrevin,
      synaptophysin, and cyclophilin B, and did not affect accumulation of others,
      including synaptotagmin I, calnexin, and glucose-regulated protein 94. The
      induction of proteins was not a coordinate event, because epidermal growth factor
      alone maximally stimulated SNAP-25 accumulation, but not that of synaptotagmin
      III. Induction of SNAP-25 accumulation occurred without an increase in its
      synthesis, and induction of cyclophilin B occurred without an increase in its
      messenger RNA accumulation, suggesting that accumulation may be caused by
      stabilization of the proteins. SNAP-25 immunofluorescence was located in the
      cytoplasm and on the plasma membrane and sometimes was heavily concentrated in
      protrusions from the cell surface, especially in hormone-treated cells. Frequenin
      immunofluorescence was also sometimes concentrated in intense patches, but did
      not colocalize with SNAP-25. Growth hormone and prolactin immunofluorescence was
      not found in the protrusions and sometimes did not colocalize with each other
      when they were present in the same cell. Hormone treatment of GH4C1 cells
      therefore induces accumulation of specific proteins in all parts of the secretory
      pathway and causes morphological changes in addition to accumulating secretory
      granules.

PMID- 10965923
TI  - Transcriptional targeting to anterior pituitary lactotrophic cells using
      recombinant adenovirus vectors in vitro and in vivo in normal and
      estrogen/sulpiride-induced hyperplastic anterior pituitaries.
AB  - The use of pituitary cell type-specific promoters is a powerful molecular tool to
      achieve pituitary cell type-specific transcriptional targeting of transgenes
      encoded by viral vectors. It has recently been proposed that transcriptional
      targeting of therapeutic genes could be harnessed as a gene therapy strategy for
      the treatment of pituitary disease. We describe the successful use of the human
      PRL promoter (hPrl) encoded within recombinant adenovirus vectors to target
      transgene expression of Herpes Simplex Virus Type 1-Thymidine Kinase (HSV1-TK) or
      beta-galactosidase to lactotrophic cells in vitro and in vivo. Functionally, the
      restriction of expression of HSV1-TK to lactotrophic tumor cells, using the hPrl
      promoter, resulted in the cell type-specific induction of apoptosis in the
      lactotrophic GH3 tumor cell line, in the presence of ganciclovir (GCV). In the
      corticotrophic AtT20 cell line, we detected neither HSV1-TK expression, nor
      apoptosis in the presence of GCV. The hPrl promoter encoded within a recombinant
      adenoviral vector also restricted transgene expression to lactotrophic cells in
      primary anterior pituitary (AP) cultures, and importantly, within the anterior
      pituitary gland in vivo. When the HSV1-TK driven by hPrl promoter was used in an
      in vivo model ofestrogen/sulpiride lactotroph induced hyperplasia within the AP
      in situ, the treatment was not effective in either reducing the weight of the
      gland, the number of lactotrophic cells within the transduced area in vivo, or
      the circulating PRL levels. This is in contrast to the human cytomegalovirus
      promoter (hCMV) driving expression of HSV1-TK in the same experimental paradigm,
      which was effective in reducing pituitary weight and circulating PRL levels. Our
      results have important implications in the design of gene therapy strategies for
      pituitary tumors. We demonstrate that both the choice of the in vivo animal
      model, i.e. adenoma in the AP gland in situ, and the particular gene therapy
      strategy chosen, i.e. use of strong ubiquitous promoters vs. weaker but cell type
      specific promoters, determine the experimental therapeutic outcome.

PMID- 10965924
TI  - Detection of estrogen receptor-beta messenger ribonucleic acid and 125I-estrogen
      binding sites in luteinizing hormone-releasing hormone neurons of the rat brain.
AB  - Luteinizing hormone-releasing hormone (LHRH) neurons of the forebrain play a
      pivotal role in the neuroendocrine control of reproduction. Although serum
      estrogen levels influence many aspects of LHRH neuronal activity in the female,
      earlier studies were unable to detect estrogen receptors (ERs) within LHRH
      neurons, thus shaping a consensus view that the effects of estradiol on the LHRH
      neuronal system are mediated by interneurons and/or the glial matrix. The present
      studies used dual-label in situ hybridization histochemistry (ISHH) and combined
      LHRH-immunocytochemistry/125I-estrogen binding to readdress the estrogen
      receptivity of LHRH neurons in the female rat. In ISHH experiments we found that
      the majority of LHRH neurons exhibited hybridization signal for the "beta" form
      of ER (ER-beta). The degree of colocalization was similar in topographically
      distinct populations of LHRH neurons and was not significantly altered by
      estradiol (67.2+/-1.8% in ovariectomized and 73.8+/-4.2% in ovariectomized and
      estradiol-treated rats). In contrast, the mRNA encoding the classical ER-alpha
      could not be detected within LHRH neurons. In addition, in vivo binding studies
      using 125I-estrogen revealed a subset of LHRH-immunoreactive neurons (8.8%) which
      accumulated the radioligand thus providing evidence for the translation of ER
      protein(s) within these cells. The findings that most LHRH neurons in the female
      rat express ER-beta mRNA and at least some are capable of binding 125I-estrogen
      challenge the current opinion that estrogen does not exert direct effects upon
      the LHRH neuronal system.

PMID- 10965925
TI  - Discovery of new inducible genes in in vitro decidualized human endometrial
      stromal cells using microarray technology.
AB  - A prerequisite for implantation in humans is differentiation (decidualization) of
      stromal cells in the endometrium, believed to be stimulated by progesterone (P)
      and/or cAMP. In the current study, advances in microarray technology have allowed
      us to investigate genes differentially expressed in human endometrial stromal
      cells decidualized in vitro in response to P or cAMP, compared to nondecidualized
      cells. Endometrial stromal cells were isolated from endometrial biopsy tissue and
      cultured without steroid hormones, with 1 microM P (after E2 priming), or 1 mM 8
      bromo-cAMP. Total RNA was isolated and reverse transcribed to synthesize 32P
      labeled cDNA probes using primers corresponding to genes represented on the
      Clontech Human Atlas cDNA Expression Array. After hybridization, signals were
      quantified by phosphor imaging densitometry and were normalized to GAPDH and
      ubiquitin. Of the 588 genes screened, marked upregulation was observed of
      cytokines, growth factors, nuclear transcription factors, members of the cyclin
      family, and mediators of the cAMP signal transduction pathway. Additional mRNAs
      expressed unexpectedly and regulated by P and cAMP, include the insulin receptor,
      some neurotransmitter receptors, neuromodulators, the FSH receptor,
      inhibin/activin betaA subunit, inhibin alpha, and TNF-related apoptosis-inducing
      ligand (TRAIL). Expression of previously unrecognized genes regulated in
      decidualized human endometrial stromal cells suggests mechanisms not yet
      appreciated in the endometrium during decidualization. In addition, marked
      upregulation of cytokines, chemokines, growth factors, apoptosis modulators, and
      their receptors in decidualized stromal cells supports a major role for paracrine
      interactions between the stroma and other endogenous and transient cell
      populations within the endometrium and during early pregnancy.

PMID- 10965926
TI  - The extracellular domain suppresses constitutive activity of the transmembrane
      domain of the human TSH receptor: implications for hormone-receptor interaction
      and antagonist design.
AB  - Among glycoprotein hormone receptors the TSH receptor (TSHR) is the most
      susceptible to constitutive activation by mutations in various regions of the
      molecule, including mutations in the extracellular domain (ECD) and extracellular
      loops of the transmembrane domain (TMD). To understand the role of the ECD in
      TSHR activation we have tested several TSHR constructs with major deletions of
      the ECD. Previous studies reported very low expression of such truncated
      glycoprotein hormone receptors, which prevented reliable assessment of their
      ligand-binding and basal constitutive activities. We have eliminated this problem
      using TSHR tagged at its N-terminus with a hemagglutinin tag (HA) recognized by
      the HA-specific monoclonal antibody. Based on such quantitation the TSHR deletion
      mutant missing 386 N-terminal amino acid residues, constituting 98% of the entire
      ECD, showed 4-7 fold higher normalized basal activity compared to activity of the
      corresponding wild-type (WT) TSHR construct. This increase in basal activity was
      significantly inhibited by linking the common alpha-subunit of glycoprotein
      hormones at the N-terminus of the truncated TSH receptor. The role of a
      hypothetical activating fragment (409-418) in TSHR activation was further studied
      using peptides and mutagenesis of charged residues. This study provides important
      evidence supporting the "two-state" model of TSHR activation and the potential
      role of proteolytic cleavage for receptor activation. Accordingly, the mechanism
      of hormone-induced receptor activation is dependent, at least in part, on the
      elimination of inhibitory interactions within the receptor. Such intra-molecular
      inhibition of TSHR may include electrostatic interactions between the ECD and
      extracellular loops of TMD. Moreover, the truncated, constitutively active
      receptors described herein provide new insights valuable in the design of TSHR
      antagonists.

PMID- 10965927
TI  - A unique metabolic syndrome causes obesity in the melanocortin-3 receptor
      deficient mouse.
AB  - The central melanocortin system is critical for the long term regulation of
      energy homeostasis. Null mutations of the melanocortin-4 receptor (MC4-R) are
      associated with hyperphagia, obesity, and accelerated longitudinal growth in mice
      and humans. However, little is known about the function of another central
      melanocortin receptor, the MC3-R. To assess the role of the MC3-R in energy
      homeostasis, the majority of the mc3r coding sequence was deleted from the mouse
      genome. In contrast to the MC4-R knockout, which exhibits increased food intake,
      increased somatic growth, and defects in metabolism, mc3r-/- mice exhibit an
      exclusively metabolic syndrome. Homozygous null mc3r mice, while not
      significantly overweight, exhibit an approximately 50% to 60% increase in adipose
      mass. Mc3r-/- mice also exhibit an unusual increase in respiratory quotient when
      transferred onto high fat chow, suggesting a reduced ratio of fat/carbohydrate
      oxidation. Furthermore, male mc3r-/- mice also exhibit an approximately 50%
      reduction in locomotory behavior on the running wheel, suggesting reduced energy
      expenditure.

PMID- 10965929
TI  - Ammonium chloride potentiation of streptozotocin-induced diabetes in juvenile
      pigs.
AB  - In preparation for direct vital microscopic evaluation of microcirculatory
      dynamics in the diabetic pig myocardium, we were initially unsuccessful in
      inducing sustained hyperglycemia in juvenile pigs using streptozotocin according
      to previously reported methods. Therefore, we modified the technique in a way
      previously unreported in an effort to improve the success rate of diabetes
      induction. In the first set of 9 pigs, we followed described methods of
      intravenous injection with 150 mg/kg streptozotocin. In the second group of 9,
      the technique was modified. The change was based on human studies with ammonium
      chloride and animal experiments with alloxan, and consisted of the addition of a
      period of pretreatment with ammonium chloride. Of the nine pigs not treated with
      ammonium chloride, only two developed sustained hyperglycemia in excess of 17
      mmol/L (300 mg/dl), and only after reinjection with a full dose of streptozotocin
      within 7 days of the first injection. Conversely, of the ammonium chloride
      pretreated pigs, eight of nine developed diabetes. We conclude that the addition
      of ammonium chloride to produce systemic acidosis prior to streptozotocin
      injection improves the efficacy of the drug.

PMID- 10965928
TI  - Metabolic response to anisoosmolarity of rat skeletal muscle in vitro.
AB  - Isolated rat hepatocytes exhibit an insulin-like anabolic response to hypoosmotic
      incubation and a glucagon-like catabolic response to hyperosmotic incubation.
      Recently, a distinct glycogenic response to hypoosmotic treatment was likewise
      reported for cultured rat myotubes. The present study examines the effects of
      anisoosmolar exposure on glucose metabolism in freshly isolated rat soleus muscle
      strips. Under the same experimental conditions as used for cultured myotubes,
      hypoosmolarity reduced net glycogen synthesis to 52%, while hyperosmolarity
      stimulated glycogen storage to 231% of isoosmolar control (nmol glucose
      incorporated into glycogen g(-1) x h(-1): hypoosmolar, 34+/-3; isoosmolar, 65+/
      8; hyperosmolar, 150+/-11; p<0.01 each vs. isoosmolar). The responses of native
      skeletal muscle to anisoosmolarity are therefore in opposition to what has been
      described for hepatocytes and cultured myotubes. Further experiments on rat
      skeletal muscle revealed that the observed lack of a glycogenic response to
      hypoosmolarity persisted independent of medium composition, specifically with
      regard to prevailing glucose and K+ concentrations. In conclusion, hypoosmotic
      exposure inhibits glycogen synthesis in isolated rat soleus muscle, which clearly
      argues against the hypothesis that osmotic changes and cell swelling may be
      physiologically relevant stimulators of muscle glycogen synthesis.

PMID- 10965930
TI  - Propranolol stimulates histone phosphorylation by a putative PK-C in partially
      purified homogenate of rat testicular interstitial cells. A possible mechanism
      for increased testosterone secretion by propranolol.
AB  - The beta-adrenoceptor blocker propranolol stimulated testosterone secretion by
      rat testicular interstitial cells (Leydig cell-enriched preparation) in vitro at
      concentrations ranging from 10(-5) M to 10(-4) M. Treatment of these cells with
      H7 (20 microM), an inhibitor of protein kinase C, reduced the stimulatory effect
      of L-propranolol on testosterone secretion by about 5-fold. At concentrations
      ranging from 31.25 microM to 1000 microM, L-propranolol reduced [3H]phorbol 12,13
      dibutyrate binding (IC50 = 75 microM) to rat testicular interstitial cells. At
      similar concentrations, L-propranolol displaced the binding of [3H]phorbol 12,13
      dibutyrate to the homogenate of these cells by only 5%. These findings suggest
      that the effect of L-propranolol on [3H]phorbol 12,13-dibutyrate binding could be
      indirect, possibly by increasing the concentration of a chemical mediator
      interacting with the regulatory domain of protein kinase C. At even lower
      concentrations (10(-9) M to 10(-7) M), propranolol added directly to the reaction
      mixture with protein kinase C partially purified from rat testicular interstitial
      cells increases the phosphorylation of histone. This phosphorylation was
      comparable to that obtained with (25 microg/ml) phosphatidylserine. The D- and L
      stereoisomers of propranolol were equally active. A complete reversal of this
      propranolol effect on histone phosphorylation was achieved with (20 microM) H-7.
      In the absence of Ca2+, propranolol was not able to phosphorylate the histone.
      Taken together, these results suggest that protein kinase C could be the putative
      kinase involved in this reaction and that its activation by propranolol may be
      due to interaction of the drug with the regulatory domain of the enzyme at a site
      differing from the site of interaction with phorbol 12,13-dibutyrate. The ability
      of propranolol to activate the putative protein kinase C could be related to its
      stimulatory effect on testosterone secretion by Leydig cells.

PMID- 10965931
TI  - Glucagon inhibits ACTH-stimulated cortisol secretion from dispersed human
      adrenocortical cells by activating unidentified receptors negatively coupled with
      the adenylate cyclase cascade.
AB  - We have investigated the direct effect of glucagon on collagenase-dispersed
      adrenocortical cells obtained from consenting patients undergoing unilateral
      adrenalectomy and nephrectomy for renal cancer. Dispersed cells, actually a
      mixture of zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells, were
      incubated with glucagon (from 10(-10) to 10(-6) M) alone or in the presence of
      10(-9) M angiotensin-II, 10(-10) M ACTH or 10(-5) M forskolin, and the effects on
      aldosterone, cortisol and cyclic-AMP (cAMP) production were measured by
      radioimmune assay. Glucagon concentration-dependently inhibited ACTH-stimulated
      cortisol production and ACTH- or forskolin-enhanced cAMP release, minimal and
      maximal effective concentrations being 10(-9) and 10(-7) M. The effects of
      glucagon were suppressed by 10(-5) M Des-His1-[Glu9]glucagon amide, an antagonist
      of glucagon receptors (glucagon-A). Reverse transcription-polymerase chain
      reaction did not reveal the presence of specific glucagon-receptor mRNA in the
      human adrenal cortex. However, autoradiography demonstrated the presence of
      [125I]glucagon binding sites in the ZF/R, which were displaced by glucagon but
      not by ACTH. Taken together, these findings suggest that glucagon, through the
      activation of unidentified receptors located on ZF/R cells, inhibits adenylate
      cyclase, thereby dampening glucocorticoid response to ACTH.

PMID- 10965932
TI  - Defective antioxidant defense system in patients with a human leptin gene
      mutation.
AB  - Antioxidant defense system prevents the organism from the detrimental effects of
      free radicals via scavenging or inhibiting their formation. Changes in the
      antioxidant defense mechanisms and alterations of several essential trace
      elements in both plasma and various tissues of ob/ob mice have been reported
      previously. Recent finding of the restoration of the defective antioxidant enzyme
      activity after leptin treatment in ob/ob mice suggests a putative role of leptin
      in modulation of antioxidant enzyme activity. Therefore, the aim of this study
      was to investigate whether antioxidant enzymes and trace elements could also be
      altered in patients with leptin gene mutation. Seven patients (five men and two
      women, two of them are homozygous and 5 are heterozygous) with leptin gene
      mutation and 31 healthy, sex- and age-matched and non-related to the patients (24
      male and 9 female), control volunteers were enrolled in the study. Plasma and
      erythrocyte glutathione peroxidase (GSH-Px) and erythrocyte copper-zinc
      superoxide dismutase (CuZn-SOD) activities were measured spectrophotometrically.
      Plasma selenium (Se), manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe)
      levels were measured by atomic absorption spectrophotometry. Mean Cu and Fe
      levels in patients were not significantly different than those in controls
      whereas mean Se, Zn and Mn levels were significantly lower in patients than those
      of controls (P=0.007, P=0.001, and P=0.001, respectively). Erythrocyte GSH-Px
      (39%), plasma GSH-Px (24%) and erythrocyte CuZn-SOD activities (32%) were
      significantly lower than those of the control group (P=0.001, P=0.002, P=0.001,
      respectively). In conclusion, our results demonstrate that the activity of
      antioxidant enzymes and plasma levels of Se, Zn and Mn levels were decreased in
      both homozygous and heterozygous subjects with leptin gene mutation. We suggest
      that both leptin and trace elements might be involved in the modulation of
      antioxidant defense system.

PMID- 10965933
TI  - Serum leptin concentrations in young insulin-sensitive and insulin-resistant
      volunteers.
AB  - The aim of this study was to compare metabolic profiles and serum leptin
      concentrations between young insulin-sensitive and insulin-resistant subjects. A
      cross-sectional study was performed in 32 healthy, non-obese, young volunteers.
      Assessing of insulin sensitivity, serum leptin concentration, serum uric acid,
      creatinine levels and lipid profile were done on all subjects. An insulin
      suppression test modified with octreotide was performed to assess insulin
      sensitivity. Steady state glucose (SSG) and steady state insulin concentrations
      were calculated. Based on the SSG data, the volunteers were divided into four
      quartiles, considering as insulin-sensitive individuals those from quartile 1 to
      quartile 3, and insulin-resistant subjects those in quartile 4. Characteristics
      of both groups were compared, including metabolic profile and leptin levels.
      After dividing SSG into quartiles, 24 subjects were considered as insulin
      sensitive individuals, and 8 were assessed as insulin-resistant subjects. Total
      cholesterol and low-density lipoprotein (LDL) cholesterol were significantly
      higher in the insulin-resistant group than in the insulin-sensitive group. Serum
      leptin concentration was significantly higher (p=0.05) in insulin-resistant women
      (6.1 +/- 3.1 ng/ml) than those considered as insulin-sensitive (3.7 +/- 2.3
      ng/ml). In conclusion, insulin-resistant subjects had higher concentrations of
      total cholesterol and LDL-cholesterol compared to insulin-sensitive individuals.
      Serum leptin level was higher in insulin-resistant women than those considered as
      insulin-sensitive.

PMID- 10965934
TI  - Methylprednisolone increases plasma leptin levels in Graves' hyperthyroidism
      patients with active Graves' ophthalmopathy.
AB  - Whether leptin, a product of the ob gene, can be stimulated by glucocorticoid
      administration has been an issue of controversy. We investigated the effect of
      intravenous administration of methylprednisolone (500 mg/day x 3 days) on plasma
      levels of leptin in 16 patients (female/male = 11/5) with Graves' hyperthyroidism
      and active ophthalmopathy who received pulse therapy. Significant elevation of
      plasma leptin levels started at the eighth hour (13.9+/-1.8 ng/mL, p=0.042) and
      lasted until the 72nd hour (21.2+/-5.0 ng/mL, p=0.009), as compared with basal
      levels (8.8+/-1.2 ng/mL). When methylprednisolone was replaced with oral
      prednisolone (10 mg three times per day x 2 weeks), no difference in plasma
      leptin levels was noted compared with basal measurement. Under methylprednisolone
      administration, a significant suppression of tumor necrosis factor-alpha began at
      the 24th hour (8.1+/-1.3 pg/mL, p=0.004) and lasted until the 48th hour (8.1+/
      1.0 pg/mL, p=0.008), as compared with basal measurement (12.5+/-1.5 pg/mL).
      Compared with basal levels (93+/-2 mg/dL), significant elevation in the plasma
      glucose level started at the third hour (135+/-10 mg/dL, p=0.000) and lasted
      until the 72nd hour (110+/-4 mg/dL, p=0.019). The timing of serum insulin
      elevation approximated that of plasma glucose (3 hours: 14+/-3 microU/mL,
      p=0.006) and lasted until the end of prednisolone administration (2 weeks: 12+/-2
      microU/mL, p=0.044), when compared with basal levels (14+/-3 microU/mL). We
      concluded that the parental administration of pharmacological doses of
      methylprednisolone to patients with Graves' hyperthyroidism could acutely raise
      their plasma level of leptin.

PMID- 10965935
TI  - Serum levels of the cytokines IL-1beta, IL-6 and ICAM-1 after 131I-treatment of
      Graves' disease and nodular goiter.
AB  - Cytokines might be involved in the immunological flare up, seen in some patients
      after 131I-treatment. Therefore, we measured serum levels of interleukin-6 (IL
      6), interleukin-1beta (IL-1beta), interleukin-6 soluble receptor (IL-6sR) and
      Intercellular-adhesion-molecule-1 (ICAM-1) as well as tumor necrosis factor (TNF
      alpha) after 131I-treatment of Graves' disease and nodular goiter. Seven patients
      with Graves' disease, eight with toxic nodular goiter and seven with non-toxic
      nodular goiter, were followed after 131I-treatment. The patients were treated in
      the euthyroid state. Blood samples were drawn at day 0, 4, 7, 21 and after 3
      months. Significant increases were seen in free T4 index (FT4I), free T3 index
      (FT3I) and thyroglobulin (Tg) within the first weeks, and TSH simultaneously
      decreased. None of the cytokines demonstrated any change during follow-up,
      neither in the entire group nor in subgroups. FT4I and FT3I correlated
      significantly to ICAM-1. In conclusion, our data suggest that there does not seem
      to be prolonged cytokine activation after 131I-treatment for thyroid disorders.

PMID- 10965936
TI  - The effect of the menstrual cycle and of ethinylestradiol on nitric oxide,
      endothelin-1 and homocysteine plasma levels.
AB  - The use of the estrogen ethinylestradiol is associated with an increased
      cardiovascular risk. It is not known whether this might be caused by an influence
      of ethinylestradiol on endothelium-derived factors or on the cardiovascular risk
      factor homocysteine. Our aim was to evaluate whether a short-term treatment with
      ethinylestradiol results in changes of nitric oxide (NO), endothelin-1 and
      homocysteine. Participants were ten healthy women with regular menstrual cycles.
      NO, homocysteine, endothelin-1, estradiol and progesterone were measured during
      one cycle and before and after treatment with ethinylestradiol at 50 microg/day.
      Homocysteine and NO did not change significantly during the menstrual cycle or
      after treatment. However, endothelin-1 levels decreased during the cycle (from
      3.89 ng/l to 2.93 ng/l p < 0.05) and after ethinylestradiol (from 2.94 ng/l to
      2.26 ng/l p<0.03). Analysis of the pretreatment data showed a positive
      correlation between homocysteine and NO and between NO and endothelin-1.
      Treatment with ethinylestradiol caused a shift in the balance between NO and
      endothelin-1 in the direction of vasodilatation. This finding is one factor
      concerning the effects of ethinylestradiol on the vascular system but does not
      explain the cardiovascular risk of this substance.

PMID- 10965937
TI  - Functional rest through intensive treatment with insulin and potassium channel
      openers preserves residual beta-cell function and mass in acutely diabetic BB
      rats.
AB  - Diazoxide and the diazoxide-analogue, NNC 55-0118, are potassium channel openers
      that interfere with insulin secretion from beta-cells. In vitro, we show that
      these two drugs inhibit insulin release from diabetes-resistant BB rat islets
      cultured at either low or high glucose concentration and cause an intracellular
      accumulation of insulin with high glucose. Preservation of beta-cells was
      investigated in newly diabetic BB rats treated with insulin implants from day 0-8
      under oral diazoxide, NNC 55-0118 or solvent gavage once a day from day 0-7.
      Three of eight rats (37.5%) treated with diazoxide and three of ten (30%) treated
      with NNC 55-0118 retained near normal C-peptide responses when challenged with
      glucose/arginine on day 9, whereas none of eight (0%) solvent-treated rats showed
      a C-peptide response. Immunohistochemical staining for insulin and glucagon
      showed that all the C-peptide responding rats had insulin-positive cells in their
      islets. In contrast, islets from non-responding rats displayed marked
      inflammation or end-stage lesions. Furthermore, rats with C-peptide response and
      treated with NNC 55-0118 exhibited only minimal signs of islet inflammation,
      whereas C-peptide responding diazoxide-treated rats had low level islet
      inflammation. These results imply that it is conceivable to preserve residual
      beta-cells at diabetes onset by induction of target cell rest with potassium
      channel openers and continuous insulin treatment.

PMID- 10965938
TI  - Phytosulfokine-alpha, a peptide growth factor found in higher plants: its
      structure, functions, precursor and receptors.
AB  - Phytosulfokine-alpha, a sulfated pentapeptide growth factor universally found in
      both monocotyledons and dicotyledons, strongly promotes proliferation of plant
      cells in culture. It is similar to animal polypeptide hormones in that it is
      processed from a larger precursor, preprophytosulfokine, although the putative
      processing sites do not conform to consensus sequences for endoproteolytic
      processing sites flanking animal prohormones. Like the animal preprohormones,
      preprophytosulfokine also has a signal peptide at the N-terminus for targeting to
      secretory pathways. The preprophytosulfokine gene has been confirmed to be
      expressed in vivo as well as in vitro.

PMID- 10965940
TI  - Mechanism of the chilling-induced decrease in proton pumping across the tonoplast
      of rice cells.
AB  - The ATP-generated proton pumping across tonoplast vesicles from chilling
      sensitive Boro rice (Oryza sativa L. var. Boro) cultured cells was markedly
      decreased by chilling at 5 degrees C for 3 d. The membrane fluidity of core
      hydrophobic and surface hydrophilic regions of the lipid bilayer was measured by
      steady-state fluorescence depolarization of 1,6-diphenyl-1,3,5-hexatriene and
      trimethylammonium 1,6-diphenyl-1,3,5-hexatriene and by electron spin resonance
      spectroscopy of 16- and 5-doxyl stearic acid, respectively. The fluidity of the
      surface region of the lipid bilayer of the tonoplast vesicles decreased by
      chilling. The fluidity of the surface region of the liposomes and the proton
      pumping across the reconstituted proteoliposomes with tonoplast H+-ATPase
      decreased with increasing content of the glycolipids. The proton pumping across
      chimera proteoliposomes was reduced by chilling only when it was reconstituted in
      the presence of tonoplast glycolipids from chilled Boro cells. These data suggest
      that the reduction in ATP-generated proton pumping across the tonoplast by
      chilling is due to the decrease in the fluidity of the surface region of the
      lipid bilayer of the tonoplast, which is caused by the changes in glycolipids.

PMID- 10965939
TI  - Jasmonate induction of putrescine N-methyltransferase genes in the root of
      Nicotiana sylvestris.
AB  - Nicotine alkaloids are synthesized in the root of Nicotiana species, and their
      synthesis increases after insect attack, wounding and jasmonate treatment of the
      leaf. Putrescine N-methyltransferase (PMT) catalyzes the first committed step in
      nicotine biosynthesis. The expression patterns of the three Nicotiana sylvestris
      PMT genes (NsPMT1, NsPMT2, and NsPMT3) are reported in this study. Transcripts of
      the NsPMT genes were detected only in the root, and were up-regulated by methyl
      jasmonate treatment. When the 5'-flanking regions of NsPMT1, NsPMT2, and NsPMT3
      were fused independently to beta-glucuronidase reporter gene and introduced into
      N. sylvestris by Agrobacterium-mediated transformation, all introduced transgenes
      were expressed in the cortex, endodermis, and xylem in the root, as well as
      upregulated by methyl jasmonate treatment. These qualitatively similar patterns
      of expression for the NsPMT genes are achieved with only 0.25 kb of their
      conserved 5'-flanking regions, which contained no known jasmonate-responsive
      elements.

PMID- 10965941
TI  - Phosphorylation of the inward-rectifying potassium channel KAT1 by ABR kinase in
      Vicia guard cells.
AB  - A 48-kDa protein kinase was detected in Vicia faba guard cell protoplasts by an
      in-gel protein kinase assay using a recombinant peptide (KAT1C) of the carboxyl
      terminus of an inward-rectifying voltage-dependent K+ channel cloned from
      Arabidopsis thaliana, KAT1. This protein kinase (ABR* kinase) was activated by
      pretreatment of guard cell protoplasts with ABA, but not by pretreatment with
      IAA, 2,4-D, kinetin or GA3. The activation of ABR* kinase was dependent on the
      time and concentration of ABA. The kinase activity was sensitive to staurosporine
      and K-252a, protein kinase inhibitors, and insensitive to Ca2+. No ABR* kinase
      activity was detected in mesophyll cell protoplasts. These characteristics of
      ABR* kinase are consistent with those of an ABA-responsive protein kinase (ABR
      kinase) reported previously [Mori and Muto (1997), Plant Physiol. 113: 833].
      These results indicate that ABR* kinase phosphorylates the inward-rectifying K+
      channel in response to treatment of stomatal guard cells with ABA. The data
      reported here provide evidence that this ABA-responsive protein kinase may
      promote ABA signaling by directly phosphorylating guard cell ion channels.

PMID- 10965942
TI  - Demonstration of Cl- requirement for inhibition of vacuolar acidification by
      cycloprodigiosin in situ.
AB  - Applying vacuole-perfusion and plasma membrane permeabilization techniques to
      internodal cells of Chara, we analyzed the requirement of Cl- for the action of
      cycloprodigiosin (cPrG) to inhibit vacuole acidification in situ. By combining
      the two techniques, the Cl- concentration on both sides of the tonoplast could be
      controlled. In permeabilized cell fragments lacking Cl- in the vacuole, the
      inhibitory effect of cPrG on vacuole acidification was cancelled. On the other
      hand, Cl- in the cytoplasm was not needed for the cPrG action. These results
      supported the function of cPrG as a H+/Cl- symporter. Requirement of Cl- for the
      cPrG action was also demonstrated in vacuole-perfused living cells. This is the
      first report on the mechanism of cPrG action in situ.

PMID- 10965943
TI  - Responses of wild watermelon to drought stress: accumulation of an ArgE homologue
      and citrulline in leaves during water deficits.
AB  - Wild watermelon from the Botswana desert had an ability to survive under severe
      drought conditions by maintaining its water status (water content and water
      potential). In the analysis by two-dimensional electrophoresis of leaf proteins,
      seven spots were newly induced after watering stopped. One with the molecular
      mass of 40 kilodaltons of the spots was accumulated abundantly. The cDNA encoding
      for the protein was cloned based on its amino-terminal sequence and the amino
      acid sequence deduced from the determined nucleotide sequences of the cDNA
      exhibited homology to the enzymes belong to the ArgE/DapE/Acy1/Cpg2/YscS protein
      family (including acetylornithine deacetylase, carboxypeptidase and aminoacylase
      1). This suggests that the protein is involved in the release of free amino acid
      by hydrolyzing a peptidic bond. As the drought stress progressed, citrulline
      became one of the major components in the total free amino acids. Eight days
      after withholding watering, although the lower leaves wilted significantly, the
      upper leaves still maintained their water status and the content of citrulline
      reached about 50% in the total free amino acids. The accumulation of citrulline
      during the drought stress in wild watermelon is an unique phenomenon in C3
      plants. These results suggest that the drought tolerance of wild watermelon is
      related to (1) the maintenance of the water status and (2) a metabolic change to
      accumulate citrulline.

PMID- 10965944
TI  - Organ and cellular localization of asparagine synthetase in rice plants.
AB  - DNA gel blot analysis suggested that asparagine synthetase (AS; EC 6.3.5.4)
      occurred as a single gene in rice. A fusion protein consisting of 17 kDa tagged
      region from pET32a(+) expression plasmid and 42 kDa N-terminal region of rice AS
      was first expressed in Escherichia coli. The resulting polypeptide was purified
      and a mono-specific antibody for rice AS was prepared after affinity-purification
      with the antigen. Immunoblotting revealed a high content of AS protein in the
      leaf sheath at the second position from the fully expanded top leaf and in grains
      at the middle stage of ripening. Accumulation of mRNA for AS was also observed in
      these organs. During the ripening of the spikelets, the AS protein contents
      increased during the first 21 days after flowering, then declined rapidly.
      Immunolocalization analysis revealed signals for AS protein in the companion
      cells of vascular bundles of leaf sheath and phloem-parenchyma cells, nucellar
      projection, and nucellar epidermis of dorsal vascular bundles of grains.

PMID- 10965945
TI  - Antisense waxy genes with highly active promoters effectively suppress waxy gene
      expression in transgenic rice.
AB  - To regulate Waxy (Wx) gene expression by introducing antisense genes, we
      connected the 2.3 kb Wx cDNA having 450 bp of the Wx first intron in reverse
      orientation to rice Wx and maize alcohol dehydrogenase1 (Adh1) promoters and used
      these constructs to transform rice plants. Of 10 independent transgenic lines
      analysed, four lines showed various degrees of reduction in amylose and WAXY (WX)
      protein levels in the endosperm. In two transgenic lines, complete absence of
      amylose was observed which made the seeds opaque white like glutinous rice
      (amylose-deficient waxy (wx) mutant). In one of the transgenic lines, A1 line,
      the presence of the antisense Wx gene cosegregated with reduction of amylose
      content in the endosperm. In the same line, a reduction in the level of
      endogenous Wx mRNA was observed in immature endosperm. Interestingly, this
      reduction was observed only with mature spliced transcripts but not with
      unspliced transcripts. Reduced amylose synthesis was also observed in pollen
      grains of four transgenic lines. These results suggest that integrated antisense
      Wx gene caused a reduction in amylose synthesis in endosperms and pollen grains
      of transgenic rice carrying the antisense Wx cDNA. These results indicate that
      manipulation of starch and other carbohydrates in rice grain is possible using
      antisense genes.

PMID- 10965946
TI  - Purification and properties of protoporphyrinogen oxidase from spinach
      chloroplasts.
AB  - Protoporphyrinogen oxidase (Protox), an enzyme that catalyzes the common step of
      chlorophyll and heme biosynthetic pathways, was purified from spinach
      chloroplasts. The molecular weight of purified protein was estimated to be
      approximately 60,000 by SDS-PAGE. Protox activity was stimulated by addition of
      FAD, suggesting that chloroplast Protox requires FAD as a cofactor. Furthermore,
      the Protox-inhibiting herbicide, S23142, specifically inhibited the purified
      Protox activity at an IC50 value of 1 nM.

PMID- 10965947
TI  - Effects of ethylene precursor and inhibitors for ethylene biosynthesis and
      perception on nodulation in Lotus japonicus and Macroptilium atropurpureum.
AB  - Inhibitors of ethylene synthesis or its physiological function enhanced
      nodulation in Lotus japonicus and Macroptilium atropurpureum. In contrast, the
      application of 1-aminocyclopropane-1-carboxylic acid, a precursor of ethylene
      biosynthesis, reduced the nodule number in these legumes. These results suggest
      that an ethylene-mediated signaling pathway is involved in the nodulation process
      even in the determinate nodulators.

PMID- 10965948
TI  - An Arabidopsis gene encoding a Ca2+-binding protein is induced by abscisic acid
      during dehydration.
AB  - An Arabidopsis thaliana RD20 cDNA, which was isolated as one of drought-inducible
      genes, encodes a putative protein with a conserved EF-hand Ca2+-binding domain.
      The recombinant RD20 protein was shown to bind Ca2+. The transcription of RD20
      gene was induced not only by drought but also by ABA and high salinity.

PMID- 10965949
TI  - Meeting report: ninth international conference on harmful algal blooms, Hobart,
      Tasmania, Australia, February 7-11, 2000.

PMID- 10965950
TI  - The nucleo morph genomes of cryptophytes and chlorarachniophytes.

PMID- 10965952
TI  - Isolation and characterisation of chemotactic mutants of Chlamydomonas
      reinhardtii obtained by insertional mutagenesis.
AB  - The swimming behaviour of the green flagellated protist Chlamydomonas reinhardtii
      is influenced by several different external stimuli including light and chemical
      attractants. Common components are involved in both the photo- and chemo-sensory
      transduction pathways, although the nature and organisation of these pathways are
      poorly understood. To learn more about the mechanism of chemotaxis in
      Chlamydomonas, we have generated nonchemotactic strains by insertional
      mutagenesis. The arginine-requiring strain arg7-8 was transformed with DNA
      carrying the wild-type ARG7 gene. Of the 8630 arginine-independenttransformants
      obtained, five are defective in their chemotaxis towards various sugars. Two of
      the mutants (CTX2 and CTX3) are blocked only in their response to xylose. Mutant
      CTX1 is blocked in its response to xylose, maltose and mannitol, but displays
      normal taxis to sucrose. Mutants CTX4 and CTX5 lack chemotactic responses to all
      sugars tested. CTX1, CTX4 and CTX5 represent novel chemotactic phenotypes not
      previously obtained using ultra-violet or chemical mutagenesis. Genetic analysis
      confirms that each mutation maps to a single nuclear locus that is unlinked to
      the mating-type locus. Further analysis of CTX4 indicates that the mutant allele
      is tagged by the transforming ARG7 DNA. CTX4 appears to be defective in a
      component specific for chemotactic signal transduction since it exhibits wild
      type photobehavioural responses (phototaxis and photoshock) as well as the wild
      type responses of EGTA-induced trans-flagellum inactivation and acid-induced
      deflagellation. Insertional mutagenesis has thus permitted the generation of
      novel chemotactic mutants that will be of value in the molecular dissection of
      the signalling machinery.

PMID- 10965951
TI  - Environmental regulation of pathways controlling sporulation, dormancy and
      germination utilizes bacterial-like signaling complexes in Dictyostelium
      discoideum.

PMID- 10965953
TI  - The 3' untranslated region of messages in the rumen protozoan Entodinium
      caudatum.
AB  - The 3' untranslated regions of a number of cDNAs from the rumen protozoal species
      Entodinium caudatum were studied with a view to characterising their preference
      for stop codons, general length, nucleotide composition and polyadenylation
      signals. Unlike a number of ciliates, Entodinium caudatum uses UAA as a stop
      codon, rather than as a codon for glutamine. In addition, the 3' untranslated
      region of the message is generally less than 100 nucleotides in length, extremely
      A+T rich, and does not appear to utilise any of the conventional polyadenylation
      signals described in other organisms.

PMID- 10965954
TI  - Flagellar membrane proteins of Tetraselmis striata butcher (Chlorophyta).
AB  - Highly purified flagella of the green alga Tetraselmis striata (Chlorophyta) were
      extracted by Triton X-114 phase partitioning. SDS-PAGE analysis revealed that
      most proteins were present in the aqueous phase, only two prominent flagellar
      membrane proteins (fmp) of apparent molecular weight 145 and 57 kDa (fmp145 and
      fmp57) were enriched in the detergent phase. Fmp145 was purified by gel
      permeation chromatography. Glycosidase treatment in combination with lectin blot
      analysis showed that fmp145 is a glycoprotein containing 3-5 N-glycans of the
      high mannose and/or hybrid type. A polyclonal antibody (anti-fmp136) was raised
      against the deglycosylated form of fmp145 and used to localize fmp145 by
      immunofluorescence and immunoelectron microscopy. Immunogold labeling showed
      fmp145 to be present between the scale layers and the flagellar membrane. During
      flagellar regeneration fmp145 is incorporated evenly and rapidly into the newly
      developing flagella. Anti-fmp136 specifically cross-reacted with flagella of only
      a subgroup of Tetraselmis strains characterized by a specific flagellar hair type
      (type II according to Marin et al. 1993) and thus could be a useful immunomarker
      for the identification of Tetraselmis strains by fluorescence microscopy.

PMID- 10965955
TI  - Paramecium GPI proteins: variability of expression and localization.
AB  - In Paramecium primaurelia, the two major classes of cell surface proteins, the
      surface antigen (SAg) and the surface GPI proteins (SGPs), are linked to the
      plasma membrane through a glycosylphosphatidylinositol (GPI) anchor. In the
      present study, we have characterized the expression of the SGPs in several
      geographical strains of P. primaurelia and P. tetraurelia at different
      temperatures, 23 degrees C and 32 degrees C. The identification of the expressed
      SGPs was performed on purified cilia, by establishing the SGP SDS-PAGE profiles
      under four different conditions: with or without their anchoring lipid, cleaved
      with a Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (PI
      PLC), and either in a reduced or in an unreduced state. This screening revealed
      the existence of specific sets of ciliary SGPs, as a function of temperature and
      the geographical origin of the strains. The SGPs the most abundant at 23 degrees
      C and 32 degrees C displayed a rapid turnover. We also looked for the presence of
      PI-PLC releasable proteins in purified cortices. In addition to the SAg and SGPs,
      the cortical fraction was shown to contain other PI-PLC releasable proteins, not
      found in the ciliary fraction, thus localized exclusively in the interciliary
      region.

PMID- 10965956
TI  - The cDNA sequences of three tetrins, the structural proteins of the Tetrahymena
      oral filaments, show that they are novel cytoskeletal proteins.
AB  - The oral filaments of the ciliate Tetrahymena consist of the tetrins, insoluble
      polypeptides with molecular masses of around 85 kD. We characterised the tetrins
      of T. thermophila by two-dimensional gels and derived a large number of peptide
      sequences by in gel digestion. Using RT-PCR techniques and RACE-PCR, the complete
      cDNA sequences of tetrins A, B and C were established. Although tetrins differ
      strikingly in protein sequence they show a common structural principle. A N
      terminal domain of 60 to 100 residues contains most of the proline residues of
      the tetrins and is probably globular. It is followed by a long alpha-helical
      domain of 620 to 640 residues which either lacks prolines or in tetrin A contains
      a single proline residue. Although this long domain has coiled coil forming
      ability, the individual heptad repeats are not extensive. Tetrins are novel
      cytoskeletal proteins unique to ciliates. Since the three tetrin sequences
      account for all 900 amino acid residues obtained by microsequencing of peptides,
      an additional major tetrin seems excluded. A minor component D is related to
      tetrin B by peptide sequences. The isoelectric variants, particularly obvious for
      tetrin A, most likely reflect post-translational modifications. These could arise
      by phosphorylation of serines and threonines in the proline rich N-terminal
      domain.

PMID- 10965957
TI  - Professor W.T. Schewiakoff: life and science.

PMID- 10965958
TI  - Hepatitis B immune globulin: the US experience.
AB  - The increasingly aggressive use of hepatitis B immune globulin (HBIg) in liver
      transplantation for hepatitis B infected patients has led to a great improvement
      in this procedure by lowering the incidence of allograft infection. In this
      article, major US studies on the use of HBIg are reviewed, including clinical
      results, clinical failures and problems, and the remaining information still
      needed for optimal therapy. Several major clinical findings have resulted from
      these studies. (1) With a high dose of HBIg and continuous use of this agent, it
      is possible to prevent recurrence in hepatitis B virus DNA-positive patients. (2)
      It is difficult to predict the required post-transplant dose of HBIg or the
      recurrence of hepatitis B in allografts. (3) While passive immunization of HBIg
      can help achieve successful transplants of patients suffering from hepatitis B
      cirrhosis, there are two typical patterns of failure: allograft infection with
      wild-type hepatitis B virus in the early perioperative period and with a mutant
      virus more than 6 months post-transplantation. These problems appear to arise
      only in patients with pre-transplant viral replication. (4) Combination therapy
      of HBIg and lamivudine seems promising for further improvement of liver
      transplantation. (5) There are still unanswered questions concerning the
      combination strategy: optimal timing, patient selection, duration of therapy, and
      the risk of viral mutations and adverse events. In addition, the role of changing
      immunosuppression protocols in improving transplantation of hepatitis B infected
      patients has not been determined.

PMID- 10965959
TI  - European hepatitis B immunoglobulin trials: prevention of recurrent hepatitis B
      after liver transplantation.
AB  - Orthotopic liver transplantation is used for treatment of liver cirrhosis and
      organ failure due to chronic hepatitis B infection. However, in the absence of
      effective antiviral therapy, patients can develop recurrent hepatitis B leading
      to graft failure. In this report, a review is presented of several European
      studies that have demonstrated the efficacy of hepatitis B immunoglobulin (HBIg)
      in lowering the rate of recurrence or the severity of the recurrent infection.
      Clinical protocols and results of these studies are described in detail. Several
      important conclusions can be derived from the clinical results. HBIg is most
      effective when administered in high doses for a long time. Characteristics of the
      recipients, such as the presence or absence of viral DNA, can also affect the
      rate of recurrence. Intramuscular injection of HBIg has minimal side effects and
      results in reduced cost relative to intravenous injection.

PMID- 10965960
TI  - Prevention of de novo hepatitis B infection after liver transplantation with
      allografts from hepatitis B core antibody positive donors.
AB  - The frequent scarcity of organ donors has made it necessary to consider
      transplantation of organs that may have the potential to transmit hepatitis B
      virus (HBV) to the recipient. Previous reports have documented the probability of
      infection of particular recipient populations with transplanted livers from
      hepatitis B core antibody (anti-HBc) positive donors. Results have varied
      depending on the status of the recipients with respect to antibodies directed at
      the virus. Anti-HBc-positive and anti-HBs-positive recipients were generally
      resistant to hepatitis B infection, with the former infected at a low rate and
      the latter not at all. However, the probability of de novo HBV infection in naive
      recipients (anti-HBc-negative and anti-HBs-negative) was quite high (about 70%).
      The survival rate for infected patients is similar to those who are uninfected,
      but a significant percentage of infected patients will develop chronic hepatitis
      and a small percentage will develop allograft failure. Also reported here is a
      protocol designed to prevent the adverse consequences to naive recipients
      receiving livers from anti-HBc-positive donors. Hepatitis B immunoglobulin (HBIg)
      and lamivudine were utilized to prevent transmission of the hepatitis B virus.
      This combination has prevented de novo infections in all patients tested thus
      far. There are indications that HBIg or lamivudine may not be as effective when
      administered separately.

PMID- 10965961
TI  - Antiviral therapy to prevent and treat hepatitis B virus infection in hepatic
      allografts.
AB  - Hepatitis B infection of a liver allograft can have serious consequences
      including a negative influence on the probability of survival. Therefore, there
      is a need for very effective antiviral therapy for transplant recipients. In this
      article the early experience with nucleoside analogue antiviral agents, both to
      prevent and to treat hepatitis B in liver allografts, is reviewed. There are
      several important characteristics of these agents that are already apparent.
      Ganciclovir and famciclovir have limited efficacy in treating infections when
      they are used alone. These compounds might be beneficial if used after resistance
      develops to other drugs or when used in combination with other agents. Lamivudine
      is effective for about two-thirds of patients in preventing and treating
      hepatitis B infection in allografts. Hepatitis B immune globulin (HBIg) is known
      to increase the efficacy of lamivudine in preventing infection. A large study to
      further characterize this combination therapy is being organized. Resistance to
      famciclovir and lamivudine can occur if they are used alone for a long time. In
      order to lower the incidence of drug resistance, it may be necessary to utilize
      combinations of nucleoside analogues.

PMID- 10965962
TI  - Pharmacoeconomic analysis of HBV liver transplant therapies.
AB  - The outcome of liver transplantation for patients infected with the hepatitis B
      virus (HBV) has greatly improved over the last several years. The rate of
      allograft infection has decreased from 85 to 25%, while the post-transplant
      mortality rate due to HBV has decreased from 50% at 18 months to nearly
      nonexistent. For the most part, this result has been due to the increased dose
      and extended use of hepatitis B immunoglobulin (HBIg). Current lack of knowledge
      of the amount of HBIg monotherapy that is necessary to suppress residual virus
      has led to an expensive therapy. In our early experience, no alternative existed
      at the time of transplant for this group of recipients. Administration of HBIg
      was directed toward patient safety and optimal outcome rather than cost
      containment. The significance of the economic impact of this decision is
      discussed in this article. Analysis of institutional expenses revealed that the
      cost of HBIg to establish viral control was fairly consistent over time, despite
      the increased purchase price of the drug. Individualized dosing of HBIg was more
      expensive in the first year after transplantation compared to typical monthly
      administration protocols, but was substantially less expensive after 12 months
      due to decreased dosage needs. In addition to HBIg acquisition price, factors
      that affect expenditure for HBIg maintenance include time intervals between
      doses, purchase contracts, overhead of drug administration, and methods employed
      in determining charge structures. Combination therapies with nucleoside analogues
      may have a beneficial effect on future costs. Controlled trials to identify the
      optimum and most cost-effective therapy need to be performed.

PMID- 10965963
TI  - Management of hepatitis B virus infection in liver transplant recipients:
      prospects and challenges.
AB  - Although survival of liver transplantation for patients with hepatitis B
      infection is comparable to uninfected transplant recipients, prevention of
      hepatitis B virus (HBV) reinfection remains an important goal. In this article,
      several aspects of the hepatitis B reinfection and its management will be
      examined. Approximately 50% of the treatment failures that occur with hepatitis B
      immune globulin (HBIg) prophylaxis are due to mutations in the 'a' determinant of
      the HBV. In patients without mutations, failure of HBIg therapy may relate to the
      frequency and dose of HBIg, the type and amount of immunosuppression, and the pre
      transplant replication status. Antiviral therapy with lamivudine and famciclovir
      has been used successfully to treat patients who have failed HBIg treatment and
      as monotherapies for liver transplant recipients. Combining antiviral and
      immunomodulatory therapies appears efficacious, at least in the short term. New
      developments related to immunotherapy predict three potential trends in future
      use: 1) i.v. formulated HBIg, 2) monoclonal antibodies, or 3) hepatitis B immune
      plasma. In conclusion, there are an increasing number of therapeutic options for
      the management of patients undergoing liver transplantation for hepatitis B
      infection. Continued improvement in patient outcomes requires further
      understanding of each therapeutic agent and the specific patient characteristics
      that may influence efficacy.

PMID- 10965964
TI  - Case studies in orthotopic liver transplantation for hepatitis B: a panel
      discussion.
AB  - Five cases that were referred to the Division of Transplantation at NYU School of
      Medicine for consideration for liver transplantation were discussed among a panel
      of hepatitis B and liver transplant experts. Opinions were obtained on the
      management at every stage of treatment of patients with the following initial
      information: Case one: young Asian woman in stage IV hepatic coma; intubated;
      prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT):
      8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg)
      positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis
      with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface
      antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e
      antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three:
      Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites
      controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb
      negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker;
      cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type
      O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five:
      40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17
      s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative
      hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and
      around the clock during the first post-operative week; required huge doses of
      hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss
      of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen
      (BUN) 127, creatinine 3, mental status changes.

PMID- 10965965
TI  - Na+, K+-ATPase isozyme diversity; comparative biochemistry and physiological
      implications of novel functional interactions.
AB  - Na+, K+-ATPase is ubiquitously expressed in the plasma membrane of all animal
      cells where it serves as the principal regulator of intracellular ion
      homeostasis. Na+, K+-ATPase is responsible for generating and maintaining
      transmembrane ionic gradients that are of vital importance for cellular function
      and subservient activities such as volume regulation, pH maintenance, and
      generation of action potentials and secondary active transport. The diversity of
      Na+, K+-ATPase subunit isoforms and their complex spatial and temporal patterns
      of cellular expression suggest that Na+, K+-ATPase isozymes perform specialized
      physiological functions. Recent studies have shown that the alpha subunit
      isoforms possess considerably different kinetic properties and modes of
      regulation and the beta subunit isoforms modulate the activity, expression and
      plasma membrane targeting of Na+, K+-ATPase isozymes. This review focuses on
      recent developments in Na+, K+-ATPase research, and in particular reports of
      expression of isoforms in various tissues and experiments aimed at elucidating
      the intrinsic structural features of isoforms important for Na+, K+-ATPase
      function.

PMID- 10965966
TI  - The Ca2+-transporting activity of rat liver microsomes in response to protein
      undernutrition: implications for liver tumor promotion.
AB  - The effect of protein undernutrition on the activity of the smooth endoplasmic
      reticulum (microsomal) Ca2+-ATPase (SERCA) was investigated. After 12 weeks of ad
      libitum ingestion of low protein diet (5% protein), a significant depression (p
      <0.05) of liver ER Ca2+-ATPase activity (68.6% depression) was observed. However,
      no significant effects on cytochrome P450 activity and relative liver weight were
      found. It is proposed that low protein diet by inhibiting the rat liver SERCA
      activity, might increase the cytosolic free calcium ion concentration ([Ca2+])
      and promote the development of liver tumor. The possible mechanisms of low
      protein diet induced inhibition of SERCA activity are highlighted.

PMID- 10965967
TI  - UV-induced apoptosis in resistant HeLa cells.
AB  - Recently, apoptosis (genetically programmed cell death) induced by UV has been
      documented in some cell culture models. However, the significance of apoptosis in
      UV-induced cytotoxicity and resistance is uncertain. In this study, we
      investigated the induction of apoptosis in HeLa cells and its role in acquired UV
      resistance. The membrane receptor Fas was induced to assembly, and its immediate
      downstream target, caspase-8, was induced by UV in a dose- and time-dependent
      manner. Caspase-10, another possible candidate for forming the death-inducing
      signaling complex with Fas, was also activated in a dose- and time-dependent
      manner. There was significant activation of caspase 9, 3 and 2 by UV. The
      apoptotic pathways appeared to be normal in acquired UV-resistant HeLa cells. In
      addition, there was a UV dose-dependent induction of chromatin condensation in
      both parental and UV-resistant cells. However, resistant cells displayed
      significant reduction in chromatin condensation at lower doses. Inhibition of
      caspase-3 activation by specific inhibitor significantly reduced the chromatin
      condensation in both cell types, and unexpectedly, the difference between the two
      cell lines was completely eradicated, suggesting that the caspase-3 pathway plays
      a significant role in reducing apoptosis in resistant cells. The results indicate
      that UV induces apoptosis by direct activation of apoptotic proteins in HeLa and
      resistant cells. Although resistant cells displayed partial inhibition of UV
      induced apoptosis through the caspase-3 pathway, there was no consistent
      difference in the activation of this and related caspase-9 caspases compared to
      parental HeLa cells.

PMID- 10965968
TI  - Ligand binding characteristics of a glycosylphosphatidyl inositol membrane
      anchored HeLa cell folate receptor epitope-related to human milk folate binding
      protein.
AB  - The folate receptor (FR) in HeLa cells was characterized as to ligand binding
      mechanism, antigenic properties and membrane anchor in order to obtain
      information to be used for the design of biological agents targeting FR in
      malignant tumors. The receptor displayed the following binding characteristics in
      equilibrium dialysis experiments (37 degrees C, pH 7.4) with [3H] folate: a high
      affinity type of binding that exhibited positive cooperativity with a Hill
      coefficient > 1.0 and an upward convex Scatchard plot, a slow radioligand
      dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition in the presence of
      other folates. The molecular size of the receptor was 100 kDa on gel filtration
      with Triton X-100, or similar to that of high molecular weight human milk folate
      binding protein (FBP). The latter protein represents a 25 kDa molecule which
      equipped with a hydrophobic glycosylphosphatidyl inositol (GPI) membrane anchor
      susceptible to cleavage by phosphatidylinositol specific phospholipase C (PI-PLC)
      forms micelles of 1kDa size with Triton X-100. The HeLa cell FR immunoreacted
      with antibodies against purified human milk FBP in ELISA, and in a fluorescence
      activated cell sorting system, where HeLa cells exposed to increasing
      concentrations of antibody showed a dose-dependent response. Exposure to PI-PLC
      decreased the fraction of immunolabeled cells indicating a linkage of FR to cell
      membranes by a GPI anchor. HeLa cells incubated with radiofolate showed a
      continuous uptake with time, however, with a complete suppression of uptake in
      the presence of an excess of cold folate. Prewash of cells at acidic pH to remove
      endogenous folate increased the uptake. Binding and uptake of [3H] folate was
      increased in cells grown in a folate-deprived medium. The HeLa FR seems to be
      epitope related to human milk FBP.

PMID- 10965969
TI  - Both intra- and extracellular Ca2+ participate in the regulation of the lateral
      diffusion of the PDGF-beta2 receptor.
AB  - When the receptors for platelet-derived growth factor (PDGF) are activated they
      aggregate, become tyrosine-phosphorylated and elicit a cascade of down-stream
      signals, including mobilization of Ca2+ from intra- and extracellular stores.
      Receptor mobility in the plane of the membrane is a prerequisite for receptor
      aggregation and further signalling. Using human foreskin fibroblasts (AG 1523)
      and fluorescence recovery after photobleaching (FRAP), we therefore assessed the
      lateral mobility characteristics of PDGF-beta2 receptors by their diffusion
      coefficient (D), and fraction of mobile receptors (R). This was done on cells
      stimulated with either normal human serum (NHS) or PDGF under different Ca2+
      conditions. The results suggest that both intra- and extracellular free Ca2+
      influence the mobility characteristics of the PDGF-beta2 receptor. Interestingly,
      the extracellular Ca2+ seems to impose general restrictions on the mobility of
      receptors, since R increased when extracellular Ca2+ was quenched with EGTA,
      whereas intracellular clamping of Ca2+ transients with MABTAM (BAPT/AM) primarily
      affected D. When both intra- and extracellular Ca2+ were quenced, D remained low
      and R high, further supporting the proposition that they achieve distinct
      effects. Inhibition of tyrosine phosphorylation with Erbstatin, partly inhibited
      the NHS effects and released PDGF-induced receptor immobilization. Ratio imaging
      with Fura-2 displayed that both NHS and PDGF induced changes in intracellular
      free [Ca2+]. In view of the present data it might have important effects on the
      state of the receptor in the membrane, for instance by regulating its lateral
      mobility, communication with other receptors and signalling functions in the
      membrane.

PMID- 10965970
TI  - Which cholesterol level is related to the lowest mortality in a population with
      low mean cholesterol level: a 6.4-year follow-up study of 482,472 Korean men.
AB  - To evaluate the relation between low cholesterol level and mortality, the authors
      followed 482,472 Korean men aged 30-65 years from 1990 to 1996 after a baseline
      health examination. The mean cholesterol level of the men was 189.1 mg/100 ml at
      the baseline measurement. There were 7,894 deaths during the follow-up period. A
      low cholesterol level (<165 mg/100 ml) was associated with increased risk of
      total mortality, even after eliminating deaths that occurred in the first 5 years
      of follow-up. The risk of death from coronary heart disease increased
      significantly in men with the highest cholesterol level (> or =252 mg/100 ml).
      There were various relations between cholesterol level and cancer mortality by
      site. Mortality from liver and colon cancer was significantly associated with a
      very low cholesterol level (<135 mg/100 ml) without any evidence of a preclinical
      cholesterol-lowering effect. With lengthening follow-up, the significant relation
      between a very low cholesterol level (<135 mg/100 ml) and mortality from stomach
      and esophageal cancer disappeared. The cholesterol level related with the lowest
      mortality ranged from 211 to 251 mg/100 ml, which was higher than the mean
      cholesterol level of study subjects.

PMID- 10965971
TI  - Invited commentary: low cholesterol and nonartherosclerotic disease risk: a
      persistently perplexing question.
AB  - In contrast to clinical trials using statin drugs, which suggest that cholesterol
      lowering from high to moderate levels is safe, many, but not all, prospective
      studies report higher nonatherosclerotic disease rates in people with low serum
      total cholesterol, even after deleting deaths in the 5 years after cholesterol
      determination. A perplexing and unanswered question is whether low cholesterol is
      causally related to nonatherosclerotic disease risk. Cholesterol is reduced
      during the acute phase reaction; a state of immune activation that persists for
      more than 5 years may explain the prospective observations. Higher cholesterol
      may be a marker for other protective substances such as fat-soluble antioxidants.
      Low cholesterol might mark poor nutrition, for example, during depression.
      Alternatively, higher cholesterol levels may result in enhanced delivery of
      lipids to cells during the immune response or tissue repair or may enhance
      defense against endotoxins and viruses. Although we believe that populationwide
      efforts to lower cholesterol should continue, we think that important biology may
      be reflected in the repeatedly observed associations of low cholesterol with
      nonatherosclerotic disease. The authors urge that research continue to elucidate
      any biologic bases of these relations.

PMID- 10965972
TI  - Body size and breast cancer risk in black women and white women: the Carolina
      Breast Cancer Study.
AB  - The relation between body size and breast cancer risk was investigated in a
      population-based, case-control study of Black women (350 cases, 353 controls) and
      White women (523 cases, 471 controls) from North Carolina, aged 20-74 years in
      1993-1996. Logistic regression analyses compared tertiles of each body size
      variable, adjusting for age and breast cancer risk factors (results shown for
      highest relative to lowest tertile). Among premenopausal women, body mass index
      (kg/m2) was inversely associated with breast cancer (odds ratio (OR) = 0.46, 95%
      confidence interval (CI): 0.26, 0.80) for Whites but not for Blacks. There was
      essentially no association among postmenopausal women. Higher waist/hip ratio,
      adjusted for body mass index, increased risk for all women. Odds ratios for Black
      and White premenopausal women were 2.50 (95% CI: 1.10, 5.67) and 2.44 (95% CI:
      1.17, 5.09), respectively; odds ratios for Black and White postmenopausal women
      were 1.62 (95% CI: 0.70, 3.79) and 1.64 (95% CI: 0.88, 3.07), respectively.
      Findings for body mass index differed among Black women when stratified by age
      (<50 years) (OR = 0.50, 95% CI: 0.25, 1.01) instead of menopausal status. Thus,
      the associations of breast cancer with body mass index and waist/hip ratio among
      Black women are similar to those documented for Whites, despite different body
      size profiles on average.

PMID- 10965973
TI  - Reproductive factors and risk of papillary thyroid cancer in women.
AB  - The authors conducted a population-based case-control study of 410 women residing
      in three counties in western Washington State who were aged 18-64 years when
      diagnosed with papillary thyroid cancer in 1988-1994 and 574 controls to assess
      the effects of pregnancy history and other aspects of reproductive life on risk
      of this disease. Among women aged 45-64, the authors observed no associations
      with number of live births, age at first live birth, or age at last live birth.
      Risk was somewhat increased in women <45 years who had given birth within the
      previous 5 years; this association was most evident among women who reported that
      cancer symptoms had led to diagnosis. Among women who had given birth within the
      last 5 years, risk was greatest among those with two or more births during that
      time period (relative risk (RR) = 4.2, 95% confidence interval (CI): 2.0, 8.9,
      relative to parous women whose last birth was >5 years before the reference
      date). Risk of thyroid cancer was also associated with lactation during the
      previous 5 years (e.g., RR = 2.9, 95% CI: 1.5, 5.5, among parous women who had
      breastfed > or =12 months, vs. 0-1 months, during that interval). Our results
      suggest that thyroid stimulation during both pregnancy and lactation may result
      in a transient increase in risk of papillary thyroid cancer.

PMID- 10965974
TI  - Effect of alcohol intake on bone mineral density in elderly women: The EPIDOS
      Study. Epidemiologie de l'Osteoporose.
AB  - To study potential associations between alcohol consumption and bone mineral
      density in women aged 75 years or older, the authors analyzed 7,598 ambulatory
      women (mean age, 79.9 years; standard deviation, 3.8 years) recruited at five
      centers in France between 1992 and 1994. The current alcohol intake was assessed
      using a self-questionnaire. Bone mineral density was measured by dual-photon X
      ray absorptiometry of the proximal femur and total body and adjusted for age,
      weight, and height (Z score). Compared with nonusers, women who drank 11-29 g of
      alcohol per day (g/day) had higher bone mineral density values at the
      trochanteric site (p = 0.0017). Neither 1-10 g/day nor >30 g/day users had
      increased bone mineral density levels. These results were unrelated to estrogen
      replacement therapy use, dietary calcium intake, current smoking status, usual
      physical activity, educational attainment, household monthly income, and general
      health status. Alcohol intake was not associated with bone mineral density at the
      femoral neck. Total body bone mineral density was lower in subjects with alcohol
      intakes >30 g/day (p = 0.047). Our data suggest that moderate drinking (e.g., 1-3
      glasses of wine per day) is associated with an increase in trochanteric bone
      mineral density in elderly ambulatory women. However, higher intakes may have
      detrimental effects on bone mass.

PMID- 10965975
TI  - Associations of substance use, abuse, and dependence with subsequent suicidal
      behavior.
AB  - General population survey data are used to disaggregate the associations of
      substance use disorders with suicide attempts in order to evaluate a number of
      hypotheses about the processes leading to these associations. Data are from the
      US National Comorbidity Survey (1990-1992). Discrete-time survival analysis is
      used to study the effects of retrospectively reported temporally prior substance
      use, abuse, and dependence in predicting first onset of suicidal behavior.
      Alcohol and drug use predict subsequent suicide attempts after controlling for
      sociodemographics and comorbid mental disorders. Previous use is not a
      significant predictor among current nonusers. Abuse and dependence are
      significant predictors among users for three of the 10 substances considered
      (alcohol, inhalants, and heroin). The number of substances used is more important
      than the types of substances used in predicting suicidal behavior. Disaggregation
      shows that the effects of use are largely on suicidal ideation and nonplanned
      attempts among ideators. In comparison, the effects of use on suicide plans and
      planned attempts among ideators are not significant. Clinicians need to be aware
      that current substance use, even in the absence of abuse or dependence, is a
      significant risk factor for unplanned suicide attempts among ideators.

PMID- 10965976
TI  - Comparison of computer-assigned Minnesota Codes with the visual standard method
      for new coronary heart disease events.
AB  - The Minnesota Code is the most widely used electrocardiogram (ECG) classification
      system for epidemiologic studies and has been incorporated into several Computer
      algorithms. The authors compared the Modular ECG Analysis System (MC-MEANS) and
      NOVACODE computer ECG findings with the Visual coding standard for agreement and
      prognostic associations with coronary heart disease (CHD) events occurring during
      follow-up from 1987 to 1995 in 2,116 individuals participating in the
      Atherosclerosis Risk in Communities (ARIC) Study. The exact agreement between
      Visual and computer findings was greater than 90% for all Minnesota Code
      categories except Q-code, which was 77% for MC-MEANS and 81% for NOVACODE.
      Approximately 60% of all Q-codes were assigned by computer methods only. Among
      the 2,116 participants, there were 246 (11.6%) new coronary events. Unadjusted
      relative risks for codes assigned by the three methods were similar. When
      computer methods disagreed on code severity, the CHD occurrence rates for MC
      MEANS-detected severer code versus NOVACODE-detected severer code were 21% and
      7%, respectively. This study provides clear evidence that computers assign more
      and severer Minnesota Codes with similar prognostic importance as does the Visual
      method; it also alerts researchers to potential problems in pooling Minnesota
      Code data read by different methods.

PMID- 10965977
TI  - Air quality and pediatric emergency room visits for asthma in Atlanta, Georgia,
      USA.
AB  - Pediatric emergency room visits for asthma were studied in relation to air
      quality indices in a spatio-temporal investigation of approximately 130,000
      visits (approximately 6,000 for asthma) to the major emergency care centers in
      Atlanta, Georgia, during the summers of 1993-1995. Generalized estimating
      equations, logistic regression, and Bayesian models were fitted to the data. In
      logistic regression models comparing estimated exposures of asthma cases with
      those of the nonasthma patients, controlling for temporal and demographic
      covariates and using residential zip code to link patients to spatially resolved
      ozone levels, the estimated relative risk per 20 parts per billion (ppb) increase
      in the maximum 8-hour ozone level was 1.04 (p < 0.05). The estimated relative
      risk for particulate matter less than or equal to 10 microm in aerodynamic
      diameter (PM10) was 1.04 per 15 microg/m3 (p < 0.05). Exposure-response trends (p
      < 0.01) were observed for ozone (>100 ppb vs. <50 ppb: odds ratio = 1.23, p =
      0.003) and PM10 (>60 microg/m3 vs. <20 microg/m3: odds ratio = 1.26, p = 0.004).
      In models with ozone and PM10, both terms became nonsignificant because of
      collinearity of the variables (r= 0.75). The other analytical approaches yielded
      consistent findings. This study supports accumulating evidence regarding the
      relation of air pollution to childhood asthma exacerbation.

PMID- 10965978
TI  - Measles outbreak in a northern Pakistani village: epidemiology and vaccine
      effectiveness.
AB  - In the spring of 1990, local community health workers reported a measles outbreak
      in several partially vaccinated villages in the Punial Valley in northern
      Pakistan. The authors conducted an investigation in one of these villages to
      assess vaccine coverage and vaccine efficacy and to describe the patterns of
      measles outbreaks that prevailed in this community. The results of a survey of
      the entire village revealed two major gaps in vaccine coverage: the small
      minority Sunni community and children over 3 years of age. Vaccine efficacy was
      estimated to range from 73 to 90% but was markedly reduced in children who were
      vaccinated under 12 months of age. The occurrence of an outbreak in a community
      in which a relatively new vaccination program is primarily directed at younger
      children has been predicted by theoretical models of measles dynamics and is
      consistent with the experience of other vaccination programs in the developing
      world. These observations suggest that, in some areas of the developing world,
      the age groups targeted to receive measles vaccinations may need to be broadened
      to ensure adequate coverage to prevent recurrent outbreaks.

PMID- 10965979
TI  - Chronic atrophic gastritis and Helicobacter pylori infection among Japanese
      Americans in Seattle.
AB  - Gastric cancer is still a major cause of mortality due to cancer worldwide. The
      most common type of gastric cancer is intestinal type carcinoma, which usually
      occurs in stomachs containing chronic atrophic gastritis. Individuals with
      chronic atrophic gastritis are considered to be at increased risk for developing
      intestinal type carcinoma of the stomach. To examine the association between
      chronic atrophic gastritis and other gastric cancer risk factors, a cross
      sectional study was conducted using serum samples and questionnaire information
      collected from 776 persons of full Japanese ancestry in the greater Seattle area
      in 1994. The presence of chronic atrophic gastritis and Helicobacter pylori
      infection was determined by measurement of serum pepsinogen levels and H. pylori
      antibodies, respectively. Based on multiple logistic regression, the significant
      predictors of chronic atrophic gastritis were age over 50 years, H. pylori
      infection, and 20 years or more lived in Japan. Alcohol consumption, smoking,
      prior peptic ulcer, and history of gastric cancer in parents were not
      significantly associated with chronic atrophic gastritis. The results imply that
      H. pylori infection since earlier life and other unknown exposure factors in
      Japan might have played an important role in the development of chronic atrophic
      gastritis.

PMID- 10965980
TI  - Re: "Seeking causal explanations in social epidemiology".

PMID- 10965981
TI  - The synthetic peptide related to the central part of human interleukin-2 molecule
      accelerates growth and vascularization of sarcoma 180 in mice.
AB  - The synthetic peptide C-1-6 related to the central part of human interleukin 2
      molecule (sequence 59-72; N- and C-modified) had been shown previously to inhibit
      cytotoxic activity of macrophages converting them to synthesis of growth factors.
      In this paper the effect of C-1-6 on growth of sarcoma 180 in mice was studied. C
      1-6 significantly accelerated tumor growth having been injected into mice in dose
      5 or 50 microg per animal since the 4th day after tumor cells transplantation.
      Supernatants of Mphi in vitro activated by C-1-6 (10 microg/ml) and injected into
      mice also accelerated significantly sarcoma mass diurnal increasing as compared
      to mice treated with supernatants of non-activated Mphi or activated with
      bacterial lipopolysaccharide. A single injection of C-1-6 into mice either at the
      day or at the next day of tumor cells inoculation increased significantly the
      number of vessels growing up to transplant, thus the forming of the vascular bed
      had preceded tumor volume enlargement.

PMID- 10965982
TI  - Serial transplants of DMBA-induced mammary tumors in fischer rats as model system
      for human breast cancer: V. Myoepithelial-mesenchymal conversion during passaging
      as possible cause for modulation of pineal-tumor interaction.
AB  - An elevation of melatonin secretion parallel to an enhanced production of
      macrophage-derived biopterin was observed in female F344 Fischer rats bearing
      passage 2 serial transplants derived from a malignant mammary tumor induced by
      7,12-dimethylbenz[a]anthracene (DMBA). As opposed to that both parameters were
      depressed at passage 12. These results indicate the presence of divergent
      immunoneuroendocrine interactions during different phases of tumor growth. Since
      these biochemical events must have their common origin in changes taking place
      within these tumor transplants the current histopathological study was initiated.
      The primary tumor used for serial transplantation was a moderately differentiated
      adenocarcinoma of the mammary gland showing cytokeratin-positive epithelial
      components located in the inner epithelial tubule layer. In addition, bland
      looking round or elongated actin-positive myoepithelial cells were detected which
      apart from epithelial cells are known to constitute the main cellular components
      of the mammary ductal system which resemble smooth muscle cells both
      morphologically and functionally. The tumor of passage 1 showed glandular
      tubules, lined by an inner epithelial layer, and many nests of clear, bland
      looking actin-positive myoepithelial cells lying around tubules as well as in the
      stroma between actin-negative epithelial elements. The tumor of passage 2 used
      for transplantation consisted of a chaotic mixture of epithelial carcinomatous
      cells, forming a few irregular small tubules or solid nests, and, predominantly,
      of elongated plump or spindle-shaped, "myoid" atypical myoepithelial cells with a
      strong actin-positive reaction and some of these cells showed a focal vimentin
      expression. The tumor was characterized as a carcinosarcoma. At passage 12
      epithelial cells were not identified. The tumor displayed features of a
      pleomorphic sarcoma consisting mainly of giant cells with bizarre nuclei being
      cytokeratin- and desmin-negative, weakly vimentin-positive but strongly actin
      positive. These results indicate that DMBA-induced mammary tumor cells in female
      F344 Fischer rats undergo dramatic morphological changes during serial
      transplantation characterized by a total loss of malignant epithelial
      (carcinomatous) cells and the emergence and subsequent predominance of malignant
      (sarcomatous) mesenchymal cells. It appears that these sarcomatous cells develop
      out of myoepithelial cells since atypical myoepithelial cells with a strong actin
      positive reaction showed a focal vimentin expression at passage 2 indicating
      myofibroblastic differentiation as part of mesenchymal transition. The loss of
      epithelial cell elements as well as a parallel transition of myoepithelial to
      mesenchymal cell elements during passaging could lead to a lack of immunological
      recognition of these tumor transplants and to depression of melatonin. Possible
      mechanisms involved in these phenomena as well as the relevance of these findings
      for a better understanding of the role of melatonin in human mammary cancer are
      discussed.

PMID- 10965983
TI  - Changes of enzyme activities in the myocardium and skeletal muscle fibres of
      cardiomyopathic hamsters. A cytophotometrical study.
AB  - Cytophotometrical measurements of enzyme activities were performed in the
      myocardium and skeletal muscle fibres from normal and cardiomyopathic hamsters
      (BIO 8262) during ageing from 12-14 to 120-190 days. Myocardium as well as vastus
      lateralis muscles of cardiomyopathic hamsters showed changes in enzyme
      activities. The skeletal muscle fibres were typed into slow-oxidative, fast
      oxidative glycolytic and fast-glycolytic to investigate fibre type-related
      changes in muscles of cardiomyopathic hamsters. The following myopathic changes
      were mainly found: Myofibrillic ATPase was depressed in the myocardium of both
      ventricles in all investigated age stages. The ATPase activity of the right
      ventricle was more decreased than that of the left one. Additionally, a metabolic
      shift was observed in myocardium and slow-oxidative muscle fibres at the onset of
      clinical symptoms, which appeared from day 150 to day 190. During the period from
      42 up to 190 days of life an increase of oxidative (succinate dehydrogenase)
      activity was measured in the myocardium of both ventricles and in slow oxidative
      fibres of vastus lateralis muscle as a proximal muscle. At earlier ages, the fast
      fibres of myopathic vastus lateralis muscle showed higher glycolytic (glycerol-3
      phosphate dehydrogenase) activity than those of normal muscles. However, at the
      age of 120-190 days the metabolic profile of fast fibres was normalized. In
      gastrocnemius muscle as a distal muscle no changes of enzyme activities were
      measured, suggesting the investigated hereditary myopathy effected proximal, but
      not distal muscles.

PMID- 10965984
TI  - Beneficial effects of GM1 ganglioside on photochemically-induced microvascular
      injury in cerebral cortex and hypophysis in rat.
AB  - Gangliosides, the glycophospholipids which are abundantly present in the central
      nervous system, have been shown to stimulate neuronal regeneration and counteract
      the deleterious effects of ischemia on cerebral neurons. The further elucidate
      the mechanism of action of gangliosides in cerebral ischemia, we investigated the
      influence of GM1 ganglioside in the model of photochemically-induced
      microvascular injury in rat brain. The animals were injected with rose Bengal and
      illuminated through cranium with halogen lamp. This treatment resulted in the
      development of microthrombi and alterations in endothelial cells in the
      microvessels. Administration of 20 mg/kg GM1 ganglioside, 1 h before the
      photochemical reaction, largely reduced subsequent microvascular damage. In
      conclusion, the GM1 ganglioside is able to prevent microvascular damage in the
      central nervous system.

PMID- 10965985
TI  - Lysosomal activity of pulmonary alveolar macrophages in acute experimental
      pancreatitis in rats with reference to positive PAF-antagonist (BN 52021) effect.
AB  - The activation of pulmonary alveolar macrophages (PAM's), might play an important
      role in severe complications of acute pancreatitis. The aim of our study was to
      assess the labilization of macrophage lysosomal membranes and release of
      lysosomal cathepsin B (CB) and N-acetyl-beta-D-hexosaminidase (NAH) into
      bronchoalveolar lavage fluid (BALF) during taurocholate acute pancreatitis (AP)
      in rats treated with PAF-antagonist--BN 52021. Total activity of CB increased by
      374% after 6 h and by 237% after 12 h of AP in lysosomal enriched fraction of
      PAM's. Fractional free activity of CB increased to 40% after 6 h and to 38% after
      12 h of AP. Free activity of CB was increased 5 fold in the supernatant of
      macrophage homogenate, and 10 fold in the supernatant of BALF after 6 h of AP.
      The values of NAH activity roughly paralleled that of CB. Treatment with BN 52021
      (5 mg x kg(-1) every 6 h i.v.) partially normalized the measured parameters. Our
      results indicate that the PAF-antagonist BN 52021 reduced the increase of total
      and free activity of lysosomal hydrolases of PAM's and partly prevented the
      labilization of their lysosomal membranes. Therefore, an important mechanism of
      BN 52021 beneficial effect in pulmonary complications of acute pancreatitis could
      be dependent on the stabilization of PAM's lysosomes.

PMID- 10965986
TI  - Age-dependent changes in glycosaminoglycan content in the skin of fasted rats. A
      possible mechanism.
AB  - It is well recognized that during fasting or aging of animals there is a
      decreased content of several extracellular matrix components in the skin,
      including glycosaminoglycans (GAGs) and decrease in biosynthesis of these
      macromolecules. The mechanism for the phenomena is not known. We considered skin
      and blood lactate as a potential candidate to control GAG metabolism in tissues.
      Energetic metabolism, reflected by NAD/NADH and lactate/pyruvate ratios is
      changed during aging or fasting and lactate inhibits at least some GAGs
      biosynthesis. Therefore we have compared the level of lactate and the ratios of
      lactate to pyruvate in the blood and skin of fasted young and fasted adult rats
      and correlated them with the content of skin glycosaminoglycans. It has been
      found that the skin of adult rats contains about 60% of GAGs found in the skin of
      young animals. Fasting of both groups of animals resulted in further decrease in
      skin GAG content. GAG content in the skin of fasted young animals was decreased
      by 30% while in fasted adult rats no significant differences were observed,
      compared to fed animals. Lactate concentration was found to be increased over 2
      fold in the skin of young fasted rats, compared to young controls. The lactate
      concentration in adult animals was not changed during fasting, although in both
      cases the lactate levels were almost 3-fold higher than in young control rats. In
      blood, lactate concentration increased by 40% during fasting of young animals
      while it decreased by about 40% during fasting of adult rats. Although no
      differences were found in blood lactate level between young and adult rats, the
      ratio of lactate/pyruvate was decreased by over 2 fold in adult rats. The
      relative differences in mean GAG content in the skin of all experimental groups
      of animals were related to the similar differences in blood glucose and
      lactate/pyruvate ratio. Therefore not only skin lactate but also blood lactate
      concentrations may reflect the extent of skin GAG biosynthesis. We have noticed
      that increase in the ratio of skin lactate/pyruvate concentration and decrease of
      the ratio in the blood is accompanied by decrease in the skin GAG content. We
      suggest that the phenomenon may result from utilization of lactate into glucose
      in the Cori cycle which regulate glucose availability for GAG biosynthesis.
      Therefore it can be suggested that lactate may participate in inhibition of skin
      GAG biosynthesis and the extent of the inhibition is reflected by the ratio of
      lactate/pyruvate concentrations both in the skin and blood.

PMID- 10965987
TI  - Islet graft-induced changes of beta-hydroxybutyrate dehydrogenase and glucose-6
      phosphatase activity in liver cells of diabetic recipient rats.
AB  - It is known that the liver is a favourable site for implantation of pancreatic
      islets since the grafted islets remain metabolically intact and provide long-term
      normoglycemia in diabetic animals. However, the long-term effects exerted by the
      grafted tissue on the host organ are not well defined. We therefore investigated
      by light and electron microscopy the effects of syngeneic islets on the host
      organ after intraportal transplantation into the liver of streptozotocin (STZ)
      induced diabetic LEW.1W rats. In addition, tissue sections of graft-bearing liver
      were stained by enzyme histochemical methods for beta-hydroxybutyrate
      dehydrogenase (HBDH) and glucose-6-phosphatase (G6Pase). At 12 weeks after
      transplantation, the changes seen in the hepatocytes surrounding the grafted
      islets were hyperproliferation and accumulation of glycogen. Hepatocytes adjacent
      to the implanted islets displayed increased HBDH activity, whereas G6Pase
      activity was variable, either decreased or increased. Increased HBDH activity was
      also observed in the periportal region and in liver cells extending to the
      central veins. The results demonstrate that intraportal islet grafts, in addition
      to normalizing glucose homeostasis, exert remarkable effects on the liver
      parenchyma of experimentally diabetic recipient rats.

PMID- 10965988
TI  - Glomerular lesions in male rabbits treated with aluminium lactate: with special
      reference to microaneurysm formation.
AB  - Novel glomerular lesions were seen in male rabbits after intravenous
      administration of aluminum lactate. Eight rabbits in the treated group were given
      0.1 mmol/kg of aluminum lactate 5 days a week for 4 weeks. The control group of 8
      rabbits was given 0.3 mmol/kg of sodium lactate by the same injection protocol.
      In the treated group, the mesangial cells in the glomerular tufts in 6 of 8
      rabbits were distended with grayish blue granular material, which was identified
      by laser microprobe mass spectrometry and acid solochrome azurine stain as an
      aluminum compound. Other consistent findings in the glomeruli included
      microaneurysm in 6 of 8 rabbits and segmental sclerosis in 6 of 8 rabbits. Less
      frequently observed glomerular changes included crescent formation, necrosis with
      calcification, fibrosis of the Bowman's capsule, cystic dilation of the Bowman's
      space, and exudation of erythrocytes into the Bowman's space. The mechanism by
      which aluminum lactate induces the glomerular changes is not certain. However,
      the pathogenesis may involve the deposition of aluminum in the mesangial cells,
      resulting in mesangiolysis which in turn causes microaneurysm. The sclerotic
      change is interpreted as a sequela of microaneurysm. The findings suggest that
      aluminum induces glomerular lesions in rabbits. This may serve as a good animal
      model to study mesangiolysis and microaneurysm formation.

PMID- 10965990
TI  - The mechanism of daunorubicin-induced inhibition of prolidase activity in human
      skin fibroblasts and its implication to impaired collagen biosynthesis.
AB  - One of the recognized side effects accompanying antineoplastic anthracyclines
      administration is poor wound healing, resulting from impairement of collagen
      biosynthesis. However, the precise mechanism of anthracyclines-induced inhibition
      of collagen synthesis has not been established. We have suggested that prolidase,
      an enzyme involved in collagen metabolism may be one of the targets for
      anthracyclines-induced inhibition of synthesis of this protein. Prolidase [E.C.
      3.4.13.9] cleaves imidodipeptides containing C-terminal proline, providing large
      amount of proline for collagen synthesis. We have found that daunorubicin (DNR)
      induced coordinately inhibition of prolidase activity (IC50 = 0.3 microM) and
      collagen biosynthesis (IC50 = 1 microM) in cultured human skin fibroblasts. The
      decrease in prolidase activity due to the treatment of confluent cells with DNR
      was not accompanied by any differences in the amount of the enzyme protein
      recovered from these cells as shown by western immunoblot analysis. Since
      prolidase is metaloprotease, requiring manganese for catalytic activity and
      anthracyclines are known as a chelators of divalent cations we considered that
      the chelating ability of anthracyclines may be an underlying mechanism for
      daunorubicin-induced inhibition of prolidase activity. In order to determine the
      ability of DNR to form complex with manganese (II), potentiometric method was
      employed based on the measurement of protonation constant by pH-metric titrated
      assay. We have found that DNR forms stable complex with manganese (II) and the
      composition of the complex of DNR with Mn (II) was calculated as 3:1. The
      constant stability value for the investigated complex was calculated as [beta(av)
      = (1.74 +/- 0.01) 10(23). The strong ability of DNR to chelate manganese may
      explain the potential mechanism for inhibition of prolidase activity,
      subsequently collagen biosynthesis and poor wound healing in patients
      administered DNR.

PMID- 10965989
TI  - HMG-CoA reductase activity in human liver microsomes: comparative inhibition by
      statins.
AB  - The aim of this study was to compare a number of vastatins, HMG-CoA reductase
      inhibitors, in human liver microsomes. HMG-CoA reductase activity was four times
      lower than the activity in untreated rat liver microsomes. Vastatins could be
      classified in this in vitro assay in three classes both in human and rat
      microsomes: the first one including cerivastatin with an IC50 of 6 nM, the second
      one with atorvastatin and fluvastatin (IC50) between 40 and 100 nM) and the third
      one containing pravastatin, simvastatin and lovastatin (IC50 between 100 and 300
      nM).

PMID- 10965991
TI  - Cardiac troponin I and cardiac troponin T increases in pigs during ischemia
      reperfusion damage.
AB  - In this study we addressed the question of whether the measurement of cardiac
      Troponin T (cTnT) and cardiac Troponin I (cTnI) is able to detect myocardial cell
      damage in an ischemia-reperfusion model in pigs. To answer the question 3 pigs
      were anaesthesized and a cardiac arrest was induced by electric fibrillation.
      After 5 minutes of global ischemia the cardiac arrest was reversed by electric
      defibrillation until normal perfusion was restored. We could clearly demonstrate
      an increase of cTnT and cTnI 30 minutes after reperfusion indicating myocardial
      injury during ischemia and subsequent reperfusion. The cTnT as well as the cTnI
      serum levels increased till 180 minutes after reperfusion. This ischemia
      reperfusion injury is likely induced by oxygen radicals generated during hypoxia
      and subsequent reperfusion We conclude from our first results that troponin
      measurements with commercial available test kits may also reflect myocardial cell
      damage in pigs as it was recently demonstrated in rats. Further studies are
      needed for correlation of troponin serum levels and histopathological damage in
      this model especially if it is used to test beneficial or toxicological effects
      of radical neutralizing drugs.

PMID- 10965992
TI  - Studies on the influence of a Se-restricted diet on the effects of long-term
      increased copper intake in guinea pigs.
AB  - Guinea pigs were exposed to Se-restriction/deficiency in combination with
      drinking water containing 200 or 300 mg Cu/l for 6-30 weeks. Under the influence
      of Se-restriction/deficiency Cu excretion by bile was diminished, the Cu content
      of the kidneys was increased and disturbances of liver function were seen in
      animals exposed for prolonged periods. Some parameters of the immune system, such
      as the phagocytic activity of peritoneal macrophages, mitogenicity of spleen
      lymphocytes and the amount of lymphatic spleen tissue were also adversely
      affected. These effects correlated in part with the liver damage and the copper
      content of the kidneys. Conclusion are drawn with respect to the Idiopathic
      Copper Toxicosis/Indian Childhood Cirrhosis.

PMID- 10965993
TI  - Lipid emulsion reduces subacute toxicity of amphotericin B: a histopathological
      study.
AB  - In previous work acute toxic effects of amphotericin B (AB) were reduced in both
      in vitro and in vivo tests when AB was associated with a triglyceride-rich
      emulsion (AB-emulsion). The present paper compares the severity of the
      histopathological alterations as determined by morphometry produced in the target
      tissues (kidneys, liver, and lungs) by AB-emulsion with those produced by the
      conventional formulation AB-deoxycholate (DOC) following subacute AB treatment.
      No morphological alterations were seen in the spleen and heart following both AB
      DOC and AB-emulsion treatment. Although the alterations in the liver, kidneys and
      lungs are basically the same for both formulations, the intensity of the changes
      varies considerably. AB-emulsion always caused statistically decreased severity
      of morphologic alterations, compared to AB-DOC by stereological measurements, for
      the three treatment regimes of AB-administration. These three treatment regimens
      consisted of 1 mg AB/kg of body weight every 48 hours for 20 days, 2 mg AB/kg of
      body weight every 48 hours for 12 days, and 2 mg AB/kg of body weight for 4
      consecutive days. Thus, these regimens consisted of total doses varying from 8-12
      mg/kg of body weight. Specifically, these morphological changes included proximal
      and distal tubular edema, inflammation and tubular cell degeneration in the
      kidney and a moderate inflammation of the portal region in the liver.
      Vacuolization of hepatocytes only occurred for AB-DOC treatment. In addition,
      acute interstitial inflammation was observed in the lungs prior to interstitial
      and alveolar edema. The intensity of the histopathological damage increase with
      the dose and with the reduction in the time interval between AB administrations.
      Abnormal serum biochemical parameters were observed for serum urea which was
      higher for both treated AB-groups, as compared to control, and for iron which was
      lower for the AB-DOC group. In conclusion, the decreased severity of the
      morphological alterations in the kidneys, liver, and lungs following subacute
      treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our
      previous results consisting of acute toxic effects induced by in vitro and in
      vivo tests with AB-emulsion treatment.

PMID- 10965995
TI  - Increased risk of second cancers following breast cancer: role of the initial
      treatment.
AB  - OBJECTIVES AND METHODS: The risk of second primary malignancies (SMN) was studied
      in a cohort of 4,416 one-year survivors of a breast cancer. The role of the
      menopausal status and of the initial treatment modalities (surgery, radiotherapy,
      and chemotherapy) was investigated. RESULTS: Excluding second primary breast
      cancer and non-melanoma skin cancer, a total of 193 (4.4%) patients developed a
      SMN between 1973 and 1992, compared with 136 expected (Standardised Incidence
      Ratio, SIR = 1.4, 95% CI (1.2-1.6)). No trend towards either an increase or a
      decrease was noted in the SIR with time after treatment (p = 0.2). The greatest
      increase in the relative risk concerned soft tissue cancers (SIR = 13.0, 95% CI:
      6.8-22.3), followed by leukaemia (SIR = 3.1, 95% CI: 1.7-5.0), melanoma (SIR =
      2.7, 95% CI: 1.4-4.8), kidney (SIR = 2.5, 95% CI: 1.2-4.5), ovary (SIR = 2.0, 95%
      CI: 1.2-3.1) and uterine tumours (SIR = 1.9, 95% CI: 1.4-2.5). The SIR was 3.0
      (95% CI 1.8-4.7) in women under 40 at the time of the breast cancer, 1.9 (95% CI:
      1.4-2.4) in those aged 40-49 and 1.2 (95% CI 1.0-1.4) in those aged 50 or more.
      In the 2,514 women who had received radiotherapy as initial treatment without
      chemotherapy, the SIR for all SMN was 1.6 (95% CI: 1.1-2.3) fold higher than in
      those who had not received radiotherapy as initial treatment. CONCLUSION: In
      conclusion, this study confirms the increased risk of second malignancies in
      women treated for a breast cancer, and particularly in those who were younger at
      the time of treatment for breast cancer. Our results also suggest that
      radiotherapy may play a role in the onset of these second lesions.

PMID- 10965994
TI  - Increased levels of intracellular iron in the brains of ApoE-deficient mice with
      closed head injury.
AB  - Previous studies have revealed that apolipoprotein E (apoE)-deficient mice have
      distinct memory deficits and neurochemical derangements and are oxidatively
      stressed prior to and following closed head injury. The objective of this study
      was to evaluate the possibility that the enhanced susceptibility of apoE
      deficient mice to closed head injury is related to impairments in their
      antioxidative iron-chelating mechanisms. ApoE-deficient and control mice were
      subjected to closed had injury, after which the extent of brain-damage and the
      level of iron-containing cells were assessed. Examination of the brain-damaged
      areas in the injured mice revealed that, by Day 3 post injury, animals of both
      groups were maximally and similarly affected. While the size of the damaged area
      of the injured control mice diminished significantly by Day 7, however recovery
      was not observed in injured apoE-deficient mice up to at least 14 days post
      injury. Histopathologically, the decrease in the damaged areas in the control
      mice was interpreted as related to decreased edema. Numbers of iron-containing
      cells at Days 3 and 7 after injury were greater in the brains of control mice
      than in the apoE-deficient mice. Whereas the number of iron-containing cells in
      injured control mice decreased at days 9 and 14-post injury, that of the injured
      apoE-deficient mice plateaued by Day 9 at a level more than two-fold higher than
      the maximal level seen for controls. The size of the damaged areas and the number
      of iron-containing cells were correlated (P < 0.03) for both mouse groups at days
      9 and 14 after injury. The data suggest that the increased susceptibility of apoE
      deficient mice to closed head injury may be due, at least in part, to impaired
      iron scavenging and sustained oxidative stress.

PMID- 10965996
TI  - Expression of different phenotypes in cell lines from canine mammary spindle-cell
      tumours and osteosarcomas indicating a pluripotent mammary stem cell origin.
AB  - Mammary spindle-cell tumours and sarcomas seem to be restricted to dogs and
      humans. Two cell lines from spontaneous primary canine mammary spindle-cell
      tumours (CMT-U304 and CMT-U309) and two cell lines from spontaneous primary
      canine mammary osteosarcomas (CMT-U334 and CMT-U335) were established to study
      the mesenchymal phenotypes of mammary tumours in the female dog. The cells from
      the spindle-cell tumours expressed cytokeratin, vimentin and smooth muscle actin
      filaments. When these cells were inoculated subcutaneously into female and male
      nude mice they formed different types of mesenchymal tumours such as spindle-cell
      tumours, fibroma and rhabdomyoid tumours (n = 6/8). The cells from the
      osteosarcomas expressed vimentin filaments and also formed different types of
      mesenchymal tumours such as chondroid, rhabdomyoid, smooth muscle-like and
      spindle-cell tumours (n = 6/10). The cell lines CMT-U304, CMT-U309 and CMT-U335
      had receptors for progesterone but none of the four cell lines had receptors for
      estrogen. All four cell lines and their corresponding primary tumours showed
      identical allelic patterns in microsatellite analysis. By in situ hybridization
      with genomic DNA we could verify that all formed tumours but one were of canine
      origin. Our results support the hypothesis that canine mammary tumours are
      derived from pluripotent stem cells.

PMID- 10965998
TI  - The growth and metastasis of human, HER-2/neu-overexpressing tumor cell lines in
      male SCID mice.
AB  - HER-2/neu is overexpressed on a variety of human adenocarcinomas and
      overexpression has been associated with a poor prognosis. For this reason, HER-2
      has become an attractive target for immunotherapy. To facilitate testing of anti
      HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the
      in vivo growth and metastatic spread of three HER-2-overexpressing human breast
      cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell
      line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.),
      intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell
      lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells
      after s.c. injection was improved by co-inoculation with Matrigel. Metastases to
      the lungs were detectable by PCR or histopathology after s.c. injection of BT474
      and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and
      SKOV3.ip1 cells. I.p. injection of HCC1954 and SKOV3.ip1 cells produced fatal
      ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells,
      resulted in infiltration of lungs and death within 9-11 weeks.

PMID- 10965997
TI  - Expression of Bcl-2 but not Bax or p53 correlates with in vitro resistance to a
      series of anticancer drugs in breast carcinoma.
AB  - Programmed cell death is an important determinant of the response to
      chemotherapy. Among the factors controlling this process, a significant role is
      played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast
      carcinomas was assessed by the histoculture drug response assay (HDRA) using
      mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and
      cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the
      drugs killing was significantly higher than that of Bcl-2-positive tumors. No
      relationship between Bax or p53 immunoreactivity and sensitivity for any of
      anticancer drugs studied was demonstrated. Immunohistochemical results regarding
      Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a
      series of anticancer drugs and might be therapeutically useful as an indicator of
      response to adjuvant chemotherapy for breast cancer.

PMID- 10965999
TI  - Pathways through which a regimen of melatonin and retinoic acid induces apoptosis
      in MCF-7 human breast cancer cells.
AB  - It has been established that melatonin (Mlt) and retinoic acid, individually,
      inhibit the proliferation of the estrogen receptor-alpha (ER alpha)-positive MCF
      7 breast cancer cell line. Our laboratory has previously demonstrated that Mlt
      and all-trans-retinoic acid (atRA) not only inhibit the proliferation, but also
      induce apoptosis of MCF-7 cells when used in a sequential regimen of Mlt followed
      24 h later by atRA. Using this same MCF-7 breast cancer cell line, we
      investigated the potential pathways through which apoptosis is being induced. We
      found that treatment of MCF-7 cells with Mlt for 24 h before the addition of atRA
      decreased the protein levels of the death suppressor, Bcl-2, and increased,
      although with different time courses, the levels of the death promoters, Bax and
      Bak; however, there was no change in the levels of the tumor suppressor gene,
      p53. MCF-7 cells treated sequentially with Mlt and atRA also demonstrated an
      enhanced sensitivity to the apoptotic effects of atRA, which did not appear to be
      due to increased expression of the retinoic acid receptors, RAR alpha or RXR
      alpha, but rather to enhanced transcriptional activity of the RAR alpha. These
      data suggest that the sequential treatment regimen of Mlt and atRA may induce
      apoptosis by modulation of members of the Bcl-2 family of proteins. Thus, this
      combinatorial regimen, which reduces the concentration of atRA needed for
      clinical efficacy while enhancing its anti-tumorigenic activity, could be of
      great therapeutic benefit, and may, in fact, specifically induce the regression
      of established breast tumors due to its apoptosis-promoting effects.

PMID- 10966000
TI  - Four-day infusion of fluorouracil plus vinorelbine as salvage treatment of
      heavily pretreated metastatic breast cancer.
AB  - AIMS: Anthracyclines-taxanes containing regimens are widely used for breast
      cancer treatment both in neoadjuvant-adjuvant setting and in metastatic disease.
      Recently high-dose chemotherapy (HDC) with autologous stem cell support has been
      introduced as adjuvant treatment for high-risk primary breast cancer and for
      selected subsets of women with metastatic disease. Therefore, salvage treatment
      for previously treated patients with progressive disease becomes even more
      problematic. A regimen of continuous infusion of fluorouracil (FU) and
      vinorelbine (VNR) has been evaluated in heavily pretreated metastatic breast
      cancer patients. PATIENTS AND METHODS: Forty-eight women, median age 52 years,
      with previously treated breast cancer entered the study. All but one received
      more than one line of prior systemic chemotherapy for metastatic disease.
      Furthermore 14 women had undergone HDC with peripheral blood progenitor cells
      transplantation in adjuvant setting (6 pts), or metastatic disease (8 pts).
      Treatment consisted of four-day infusion of FU (1000 mg/m2/day) plus VNR (20
      mg/m2/i.v. day 1 and 5), recycled every 3 weeks for a total of six courses. Drugs
      administration was discontinued for G4 toxicity, tumor progression or patient's
      refusal. RESULTS: Twenty PR and four CR for an overall response rate of 50%
      (95%C.I. 36-64%) were recorded. The therapeutic efficacy of the tested regimen
      was documented both in patients unresponsive to previous anthracyclines-taxanes
      combinations and in those relapsing after HDC. The median duration of response
      was 9 months and median survival 16 months. One third of patients experienced
      Grade-3 stomatitis-mucositis, hematological toxicity was mild and no cardiac
      toxicity was observed. Twenty-five women (52%) suffered from infusion-related
      phlebitis (in half of patients a central venous device was necessary at some
      point of the treatment program). CONCLUSIONS: The combination of FU infusion and
      VNR i.v. is an effective salvage treatment for heavily pretreated metastatic
      breast cancer patients, and may represent a valid alternative when other
      cytotoxic regimens are not feasible.

PMID- 10966001
TI  - Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix contortrix,
      inhibits breast cancer progression.
AB  - We report the results of a multidisciplinary study on the inhibitory effect of a
      snake venom disintegrin, contortrostatin, a 13.5 kDa homodimeric protein isolated
      from Agkistrodon contortrix contortrix (southern copperhead) venom, on breast
      cancer progression. We demonstrate that contortrostatin binds to integrins and
      blocks the adhesion of human breast cancer cells (MDA-MB-435) to extracellular
      matrix (ECM) proteins including fibronectin and vitronectin, but it has no effect
      on adhesion of the cells to laminin and Matrigel. Contortrostatin also prevents
      invasion of MDA-MB-435 cells through an artificial Matrigel basement membrane.
      Daily local injection of contortrostatin (5 microg per mouse per day) into MDA-MB
      435 tumor masses in an orthotopic xenograft nude mouse model inhibits growth of
      the tumor by 74% (p = 0.0164). More importantly, it reduces the number of
      pulmonary macro-metastasis of the breast cancer by 68% (p < 0.001), and micro
      metastasis by 62.4% (p < 0.001). Contortrostatin is not cytotoxic to cancer
      cells, and does not inhibit proliferation of the breast cancer cells in vitro.
      However, contortrostatin inhibits angiogenesis induced by the breast cancer, as
      shown by immunohistochemical quantitation of the vascular endothelial cells in
      tumor tissue removed from the nude mice. We have identified alpha(v)beta3, an
      important integrin mediating cell motility and tumor invasion, as one of the
      binding sites of contortrostatin on MDA-MB-435 cells. We conclude that
      contortrostatin blocks alpha(v)beta3, and perhaps other integrins, and thus
      inhibits in vivo progression.

PMID- 10966002
TI  - Predication of axillary lymph node metastasis by intravenous digital subtraction
      angiography in breast cancer, its correlation with microvascular density.
AB  - Accurate predication of axillary node status by non-invasive diagnostic method
      would be of great value in cases of breast cancer. There have been few reports
      advocating digital subtraction angiography (DSA) as specifically advantageous for
      the detection of lymph node metastasis. IV (intravenous)-DSA was carried out on
      42 patients with breast carcinoma using a DSA system with a matrix of 1024 x 1024
      pixels. When a mass became stained in the axilla, it was considered to be
      metastatic. An immunohistochemical technique with JC70 antibody to
      platelet/endothelial cell adhesion molecules was used to evaluate the
      microvascular density (MVD) of the axillary lymph nodes. IV-DSA achieved a 76.2%
      sensitivity, 85.7% specificity, and 81.0% accuracy. The average MVD with JC70
      antibody was 97.7 +/- 44.4 in metastatic and 62.9 +/- 23.6 in nonmetastatic
      nodes. MVD was significantly higher in the cancerous than in the noncancerous
      regions within lymph nodes. The MVD was 105 +/- 38.4 in DSA-N(+) cases and was
      57.8 +/- 21.9 in DSA-N(-) cases, and the difference was statistically
      significant. In conclusion, IV-DSA is a useful diagnostic modality for detection
      of axillary lymph node metastasis. This new modality predicts lymph node status
      by assessing the neovascularization of the lymph node.

PMID- 10966003
TI  - Platelet inhibitors and cardiac surgery.

PMID- 10966005
TI  - Platelet inhibitors and bleeding in cardiac surgical patients.
AB  - A variety of measures may affect bleeding and transfusion requirements in
      abciximab-treated patients. These measures include recognition of the risk
      factors for increased bleeding and transfusion requirements, use of proper
      transfusion practices, conservation or increasing of red cell mass, appropriate
      heparin dosing and protamine reversal, reversal of anticoagulation, awareness of
      factors that affect activated clotting time (ACT), and appropriate
      anticoagulation for cardiopulmonary bypass.

PMID- 10966004
TI  - Antiplatelet agents in cardiology: the choice of therapy.
AB  - BACKGROUND: The platelet-rich, intracoronary thrombus is central to the
      pathogenesis of acute myocardial infarctions, unstable angina, and the majority
      of complications of percutaneous coronary interventions. Until recently, aspirin
      was the only antiplatelet agent available to help prevent or treat these events.
      Over the past several years, there has been a substantial expansion in our
      antiplatelet armamentarium as well as in our understanding of the clinical
      importance of antiplatelet therapy in limiting the complications of intracoronary
      thrombosis. Because of this, it is likely that over the coming years, the use of
      antiplatelet therapies will continue to expand, and it may not be unusual for a
      surgeon to encounter a patient being treated with two or even three platelet
      inhibitors. CONCLUSIONS: This review will highlight the benefits and limitations
      of the currently available antiplatelet regimens: aspirin, thienopyridines
      (ticlopidine and clopidogrel), and the platelet glycoprotein IIb/IIIa inhibitors.

PMID- 10966006
TI  - Current status of cardiac surgery in the abciximab-treated patient.
AB  - BACKGROUND: Early surgical experience with abciximab and other glycoprotein (GP)
      IIb/IIIa receptor antagonists suggested a tendency toward excessive bleeding in
      patients treated with these agents. With increased use of GP IIb/IIIa inhibitors,
      cardiac surgeons have become aware of their hazards, as well as potential
      benefits, during and after cardiac surgery. Although published experience with
      the GP IIb/IIIa inhibitor abciximab is limited in scope, it suggests management
      guidelines for urgent coronary artery bypass grafting in abciximab-treated
      patients. As more urgent and elective surgical data are presented, a clearer
      picture of true bleeding risk will evolve. METHODS: Two large retrospective
      studies examining reexploration for postoperative bleeding have identified risk
      factors, including advanced age, preoperative renal dysfunction, and
      operation/reoperation other than coronary artery bypass grafting. Other risk
      factors for transfusion requirement and increased morbidity and mortality are
      emergent operation, postoperative coagulopathy, and prolonged bypass time.
      RESULTS: To minimize real and perceived bleeding effects, some authors have
      suggested delaying operation until platelet function has normalized, employing
      platelet transfusion in patients in whom delay is not possible, and exacting
      heparin management during cardiopulmonary bypass. Later reports have not noted
      increased bleeding when incorporating these modifications plus early platelet
      transfusion, if required. Further experience with abciximab removal and reversal
      may also ultimately reduce or eliminate excess transfusion requirements.
      CONCLUSIONS: Surgeons should work closely with perfusionists and
      anesthesiologists on issues of heparinization in the abciximab-treated patient.
      The apparent paradox of preserved platelet numbers and depressed platelet
      function with abciximab use has led to speculation about a role for this agent
      and other shorter-acting GP IIb/IIIa inhibitors for "platelet anesthesia" during
      cardiopulmonary bypass. With careful surgical care, GP IIb/IIIa receptor
      antagonists can maintain and improve beneficial outcomes.

PMID- 10966007
TI  - Management approaches to platelet-related microvascular bleeding in
      cardiothoracic surgery.
AB  - Patients undergoing cardiac surgery with cardiopulmonary bypass are at increased
      risk for microvascular bleeding that requires perioperative transfusion of blood
      components. Platelet-related defects have been shown to be the most important
      hemostatic abnormality in this setting. The exact association between
      preoperative use of potent platelet inhibitors and either bleeding or transfusion
      in patients undergoing cardiac surgical procedures is currently being defined.
      Laboratory evaluation of platelets and coagulation factors can facilitate the
      optimal administration of pharmacologic and transfusion-based therapy. However,
      their turnaround time makes laboratory-based methods impractical for concurrent
      management of surgical patients, which has led many investigators to study the
      role of point-of-care coagulation tests in this setting. Use of point-of-care
      tests of hemostatic function can optimize the management of excessive bleeding
      and reduce transfusion. Accordingly, point-of-care tests that assess platelet
      function may also identify patients at risk for acquired, platelet-related
      bleeding. The ability to reduce the unnecessary use of blood products and to
      decrease operative time or reexploration rates has important consequences for
      blood inventory, blood costs, and overall health care costs.

PMID- 10966008
TI  - Clinical experience in coronary bypass surgery for abciximab-treated patients.
AB  - Abciximab effectively inhibits platelet aggregation and, therefore, there is
      considerable concern regarding bleeding complications in patients who require
      coronary artery bypass graft (CABG) surgery while affected by the drug. This
      presentation reviews the available published literature regarding CABG in
      abciximab-treated patients, the clinical results of emergency CABG in 12
      patients, and management suggestions for the abciximab-treated patient requiring
      emergency surgery.

PMID- 10966009
TI  - Coronary artery bypass graft in abciximab-treated patients.
AB  - In an assessment of available literature regarding appropriate treatment
      algorithms for patients who fail cardiac interventions and require coronary
      bypass grafting with abciximab "on board," few surgeons reported significant
      variation in bleeding or other issues. There are many problems with postmarketing
      data collection, and such data would lack rigor and randomization. Prospective
      collection of data would be extremely difficult. Few patients go to surgery
      nowadays, and it is generally believed that because of the wealth of data
      supporting glycoprotein (GP) IIb/IIIa inhibition associated with percutaneous
      intervention, it would be unethical to subject patients to a placebo control in
      the catheterization laboratory. For those reasons, we returned to the clinical
      trials database and did a retrospective analysis of EPILOG and EPISTENT, the two
      studies that most appropriately reflect state-of-the-art intervention and
      abciximab use. We omitted EPIC, the original registration trial of high-risk
      angioplasty patients, because this study no longer reflects current
      recommendations regarding heparinization, abciximab administration, or groin
      care.

PMID- 10966010
TI  - Preparation of interpenetrating networks of gelatin and dextran as degradable
      biomaterials.
AB  - Gelatin and dextran were blended and crosslinked to form enzymatically degradable
      interpenetrating polymeric networks (IPNs) as materials for degradable implants.
      Several crosslinking methods were investigated including treatment with
      glyceraldehyde, thermal hardening, and chelation of dextran by divalent metal
      cations. IPNs were characterized by an equilibrium swelling method.
      Gelatin/dextran IPNs were stable at 25 degrees C and reached peak volume
      equilibrium swelling ratios up to 17 and peak weight swelling ratios up to 15.
      When swollen at 37 degrees C, the gels dissolved denoting that a network had been
      formed by physical and not chemical crosslinks.

PMID- 10966011
TI  - Smooth muscle cell adhesion to tissue engineering scaffolds.
AB  - Synthetic polyesters of lactic and glycolic acid, and the extracellular matrix
      molecule collagen are among the most widely-utilized scaffolding materials in
      tissue engineering. However, the mechanism of cell adhesion to these tissue
      engineering scaffolds has not been extensively studied. In this paper, the
      mechanism of adhesion of smooth muscle cells to these materials was investigated.
      Vitronectin was found to be the predominant matrix protein adsorbed from serum
      containing medium onto polyglycolic acid, poly(lactic co-glycolic) acid, and
      collagen two-dimensional films and three-dimensional scaffolds. Fibronectin
      adsorbed to both materials as well, although to a much lower density. Smooth
      muscle cell adhesion was mediated through specific integrin receptors interacting
      with these adsorbed proteins, as evidenced by both immunostaining and blocking
      studies. The receptors involved in adhesion included the alpha(v)beta5 to
      vitronectin, the alpha5beta1 to fibronectin and the alpha2beta1 to collagen I.
      Identification of the specific receptors used to adhere to these polymers
      clarifies why smooth muscle tissue development differs on these scaffolds, and
      may allow one to design tissue formation by controlling the surface chemistry of
      tissue engineering scaffolds.

PMID- 10966012
TI  - Comparison of the response of primary human peripheral blood mononuclear
      phagocytes from different donors to challenge with model polyethylene particles
      of known size and dose.
AB  - The response of primary human peripheral blood mononuclear phagocytes to
      challenge with polyethylene particles of known size and dose was evaluated.
      Particles with mean sizes of 0.21, 0.49, 4.3, 7.2, and 88 microm were co-cultured
      with cells for 24 h prior to the assessment of cell viability and production of
      the osteolytic mediators IL-1beta, IL-6, TNFalpha, GM-CSF and PGE2. All particle
      fractions were evaluated at particle volume (microm3) to cell number ratios of
      10:1 and 100:1 which were previously identified as being the most biologically
      active and clinically relevant. The heterogeneity of human individuals was
      clearly evident both in the profile and the magnitude of the response of the
      donors evaluated in this study (the response of donor 5 being 2- to 15-fold lower
      than that of the other donors). Only the sub-micrometre particles stimulated
      significantly enhanced cytokine secretion at the ratios tested: mean particle
      sizes of 0.49 and 0.21 microm being the most biologically active. Macrophages
      stimulated with particles outside this size range produced considerably lower
      levels of mediator. These results compared favourably with the results of earlier
      studies, which demonstrated that particles within the phagocytosable size range
      (0.1-10 microm) were the most biologically active. These results, therefore,
      confirm earlier findings and suggest that the size and volume of polyethylene
      particles are critical factors in macrophage activation. Furthermore, they
      suggest that the heterogeneity of human individuals may be another important
      factor in determining implant life and could provide the basis for a valuable
      diagnostic tool to identify those patients most at risk of implant loosening.

PMID- 10966013
TI  - Microstructure and mechanical property of synthesized hydroxyapatite prepared by
      colloidal process.
AB  - Synthesized hydroxyapatite (HAp) was prepared by the colloidal process. Mixed
      slurry composed of 25 vol% HAp powder and 75 vol% aqueous solution containing a
      small amount of polycarboxylic acid ammonium as dispersant was produced.
      Viscosity of the HAp slurry, microstructure and mechanical property of the
      synthesized HAp prepared by this process depends on the quantity of dispersant. A
      mainly uniform microstructure was obtained in both green and sintered HAp with 2
      wt% dispersant by preventing the agglomeration of powder in the slurry. A
      homogeneous microstructure was maintained even after annealing at temperatures
      between 1200 and 1400 degrees C. Maximum bending strength of 88.5 MPa was also
      obtained at an optimum dispersant concentration.

PMID- 10966014
TI  - Strengthening of glass-ionomer cement by compounding short fibres with CaO-P2O5
      SiO2-Al2O3 glass.
AB  - The purpose of this study was to determine if short fibres of CaO-P2O5-SiO2-Al2O3
      (CPSA) glass possessing a particular aspect ratio (length/diameter) could be used
      as a reinforcing agent for glass-ionomer cement. The powder of a commercial glass
      ionomer cement (not resin modified) was mixed with variously sized CPSA glass
      short fibres before mixing with the liquid of the glass-ionomer cement. The mixed
      powders containing 60 mass% CPSA glass short fibres (diameter, 9.7 +/- 2.1
      microm, aspect ratio, 5.0 +/- 0.9) obtained maximum values of 18 and 35 MPa for
      the diametral tensile strength (DTS) and flexural strength (FS) of set cements,
      respectively, after 24 h. These DTS and FS values were 1.8 and 4.5 times larger,
      respectively, than those of the set glass-ionomer cement not containing short
      fibres. Moreover, it was found that the addition of CPSA glass short fibres was
      remarkably more effective in the strengthening than electric glass (a typical
      glass fibre) short fibres. The results suggested that the CPSA glass short fibres
      acted as a reinforcing agent for strengthening the glass-ionomer cement, because
      of the shape of short fibres and reactivity between the mixing liquid and short
      fibres.

PMID- 10966015
TI  - Expression of the CD69 activation antigen on lymphocytes of patients with hip
      prosthesis.
AB  - The aim of the study was to evaluate the sensitization to metals in patients with
      Co-Cr hip prosthesis. Peripheral blood mononuclear cells (PBMC) were collected
      from 14 healthy donors and three groups of patients: 10 candidates for primary
      total joint replacements, 11 patients with well-fixed implant and 13 patients
      with aseptic loosening of the hip prosthesis. PBMCs were cultured with the metal
      ions employed for implant manufacturing and the expression of CD69 activation
      antigen on CD3/T lymphocytes was detected by flow cytometry. Chromium extract
      increased significantly the expression of CD3/CD69 phenotype in patients with
      loosening of hip prosthesis. The chromium-induced 'activation index' was higher
      in patients with loosening of hip prosthesis than in healthy donors and in pre
      implant patients. The cobalt-stimulated PBMC of patients with either well-fixed
      or loosened prosthesis had an 'activation index' significantly higher than
      healthy donors. The activation index values were used to graduate the PBMC
      response as 'normal' (> or = 0.9 and < 2), 'low' (< 0.9) and 'high' (> or = 2):
      an high-activation index was observed only in chromium-exposed PBMC of patients
      with prosthesis. Our data show that chromium released from orthopedic implants
      could be responsible for the lymphocyte sensitization and flow cytometry is an
      easy and reliable method for monitoring the hypersensitivity state in patients
      with metal prostheses. Activated lymphocytes in the peri-implant tissue are
      likely to elicit a localized immune response and contribute to maintain the
      inflammatory process evolving in the implant failure.

PMID- 10966016
TI  - Enhancing effect of chitosan on peptide drug delivery across buccal mucosa.
AB  - The buccal mucosa represents a potentially important topical route for delivery
      of peptide or protein drugs with some unique advantages such as the avoidance of
      hepatic first-pass metabolism and the acidity and protease activity encountered
      in the gastrointestinal tract. However, the bioavailabilities or relative
      potencies of intraorally administered peptides are usually quite low, unless
      permeabilizers are employed. Chitosan, a mucopolysaccharide of marine origin, has
      been claimed to act both as a bioadhesive and permeabilizer, making it a
      candidate system for mucosal drug delivery. In this study, the enhancement effect
      of chitosan in gel form for oral mucosa was investigated with a large bioactive
      peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at
      2% concentration in dilute lactic acid and TGF-beta was incorporated into the
      gel. The effect of chitosan as a permeabilizer was determined by measuring the
      flux of TGF-beta across porcine oral mucosa in an in vitro system. The
      localization of TGF-beta within the oral mucosa was determined by horizontal
      sectioning and counting. Chitosan was found to exert a marked permeabilizing
      effect on buccal mucosa for peptide drug.

PMID- 10966017
TI  - Morphology of and release behavior from porous polyurethane microspheres.
AB  - A novel biomaterial application of porous microspheres is for sustained delivery
      of biologically active agents. Recent studies have pointed out the importance of
      biomaterial porosity in promoting biocompatibility and controlling release rate
      of active agents. The objective of this research was to investigate the effect of
      chain-extending agent on the porosity and release behavior of polyurethane (PU)
      microspheres prepared using a two-step suspension polycondensation method with
      methylene diphenyl diisocyanate (MDI) as the isocyanate, polyethylene glycol
      (PEG400) as the diol, and 1,4-butanediol as the chain-extending agent. Chain
      extending agent was used to increase the ratio of hard to soft segments of the PU
      network, and its effect on microsphere morphology was studied with scanning
      electron microscopy. According to the results, porosity was significantly
      affected by the amount of chain-extending agent. The pore size decreased as the
      concentration of chain-extending agent increased from zero to 50 mole%. With
      further increase of chain-extending agent to 60 and 67%, PU chains became stiffer
      and formation of pores was inhibited. Therefore, pore morphology was
      significantly affected by variations in the amount of chain-extending agent. The
      release behavior of microspheres was investigated with diazinon as the active
      agent. After an initial burst, corresponding to 3% of the incorporated amount of
      active agent, the release rate was zero order.

PMID- 10966018
TI  - Cyclic steady state stress-strain behavior of UHMW polyethylene.
AB  - To increase the long-term performance of total joint replacements, finite element
      analyses of ultra high molecular weight polyethylene (UHMWPE) components have
      been conducted to predict the effect of load on the stress and strain
      distributions occurring on and within these components. Early models incorporated
      the monotonic behavior of UHMWPE without considering the unloading and cyclic
      loading behavior. However, UHMWPE components undergo cyclic loading during use
      and at least two wear damage modes (pitting and delamination) are thought to be
      associated with the fatigue fracture properties of UHMWPE. The objective of this
      study was to examine the fully reversed uniaxial tension/compression cyclic
      steady state stress-strain behavior of UHMWPE as a first step towards developing
      a cyclic constitutive relationship for UHMWPE. The hypothesis that cycling
      results in a permanent change in the stress-strain relationship, that is, that
      the cyclic steady state represents a new cyclically stabilized state, was
      examined. It was found that, like other ductile polymers, UHMWPE substantially
      cyclically softens under fully reversed uniaxial straining. More cyclic softening
      occurred in tension than in compression. Furthermore, cyclic steady state was
      attained, but not cyclic stability. It is suggested that it may be more
      appropriate to base a material constitutive relationship for UHMWPE for finite
      element analyses of components upon a cyclically modified stress-strain
      relationship.

PMID- 10966019
TI  - Proton spin-spin relaxation study of molecular dynamics and proteoglycan
      hydration in articular cartilage.
AB  - Spin-spin relaxation of proton magnetization in natural and deuterated articular
      cartilage is reported over a range of hydration. Information about macromolecular
      dynamics is deduced and a hydration stabilized macromolecular regime identified.
      There is good correspondence between NMR results and cartilage stoichiometry. A
      new measure for hydration of proteoglycans is found.

PMID- 10966021
TI  - Passive film on orthopaedic TiAlV alloy formed in physiological solution
      investigated by X-ray photoelectron spectroscopy.
AB  - The passive film formed by electrochemical oxidation on TiAlV alloy in
      physiological solution was studied using X-ray photoelectron spectroscopy (XPS)
      and electrochemical impedance spectroscopy (EIS). The alloy was polarised at
      different oxidation potentials in the electrochemical chamber attached to the
      spectrometer. Thus the composition of the layer formed by oxidation was analysed
      by XPS without prior exposure to air (quasi-in situ). The oxide layer was
      predominantly TiO2, which contained a small amount of suboxides TiO and Ti2O3
      closer to the inner metal/oxide interface. With increasing potential the content
      of Ti4+ species increased and that of Ti3+ and Ti2+ decreased. The content of
      titanium in TiO2 was lower than theoretically predicted due to the incorporation
      of Al2O3 in TiO2 matrix. Vanadium oxide was not identified by XPS. Angular
      resolved XPS analysis confirmed that Al2O3 is located mainly at the outer
      oxide/solution interface. The thickness of the oxide layer was dependent on the
      oxidation potential and after oxidation at 2.5 V reached 9 nm. EIS measurements
      were used to in situ characterise electronic properties of passive films over
      seven decades of frequency. A link between electronic, electrochemical and
      physiochemical properties was established.

PMID- 10966020
TI  - Intraseptal implantation of NGF-releasing microspheres promote the survival of
      axotomized cholinergic neurons.
AB  - Neurotrophic factors therapy requires their precise delivery to the targeted
      neuronal population. For this purpose, a wide range of strategies have been
      developed, and among them the stereotaxic implantation of biodegradable
      microparticles. To assess the in vivo activity of NGF-releasing PLGA
      microspheres, unloaded and NGF-loaded microparticles were implanted in the rat
      brain, near the septal cholinergic neurons, axotomized by an unilateral
      transection of the fornix-fimbria. Histological analysis at two and six weeks
      after implantation revealed a non-specific astro- and micro-glial reaction around
      the microspheres, identical for both unloaded and NGF-loaded microspheres. No
      neuronal toxicity was noticed, and healthy looking neurons were observed in
      contact with the microspheres. In the non-treated animals, the percentage of
      axotomized surviving neurons, when compared to the contralateral intact side, was
      31 +/- 2 and 27 +/- 1% at two and six weeks, respectively. Unloaded microspheres
      caused no protective nor neurotoxic effects (40 +/- 9 and 39 +/- 6% of surviving
      cholinergic neurons at two and six weeks, respectively). In contrast, NGF-loaded
      microspheres showed a significant effect on the survival of axotomized
      cholinergic neurons at two and six weeks after implantation (66 +/- 9 and 61 +/-
      5% when compared to the contralateral intact side, respectively). These results
      show that PLGA microparticles present no neurotoxicity and release sufficient
      amounts of bioactive NGF to significantly limit the lesion-induced disappearance
      of cholinergic neurons in the septum during at least six weeks. PLGA
      microparticles can be used in the future to administer neurotrophic factors in
      central nervous system disorders.

PMID- 10966022
TI  - Acute gastric dilatation revisited.
AB  - First described by S.E. Duplay in 1833, acute gastric dilatation has since been
      well documented in the literature. Several theories of the pathogenesis of acute
      gastric dilatation have been postulated. In 1842, Karl Freiherr von Rokitansky
      described the superior mesenteric artery syndrome, followed by W. Brinton in 1859
      with the atonic theory. C.R. Morris et al. introduced debilitation and anesthesia
      as predisposing factors. Although rare, gastric necrosis is the most severe
      consequence of acute gastric dilatation. Vascular insufficiency secondary to
      increased intragastric pressure is the critical factor. We report an unusual case
      of acute gastric dilatation with subsequent necrosis of uncertain etiology.

PMID- 10966023
TI  - Bile duct carcinoma: trends in treatment in the nineties.
AB  - Surgical resection provides the only known chance of cure for cholangiocarcinoma,
      and even then the 5-year survival is only 10 to 20%, and only one-third of
      patients are resectable for cure at the time of diagnosis. In recent years we
      have had considerable experience with endoscopic stenting to palliate common bile
      duct cancers. This has prompted us to evaluate our results for both endoscopic
      and surgical treatment of cholangiocarcinoma. From January 1990 through June
      1999, we reviewed our endoscopic retrograde cholangiopancreatography registry and
      the hospital records for patients we treated for cholangiocarcinoma. Fifty
      patients were identified: 45 with cholangiocarcinoma and five with gallbladder
      cancer (who were excluded). The surgical group consisted of 16 patients: in 14
      patients, resection for cure was possible whereas two had palliative procedures.
      There was one mortality (6%) and the median survival was 16 months. There have
      been no long-term surgical survivors, but 2 patients are alive at 24 months. We
      treated 29 patients with advanced disease with endoscopic stents (the endoscopic
      group) mainly for relief of obstructive jaundice. Six of 29 patients in the
      endoscopic group were critically ill and died in less than 4 weeks, whereas 23
      patients who were in better condition survived for a mean of 10 months (range 2
      84 months). We conclude that for common duct bile cancer surgical resection
      remains the treatment of choice but is applicable in only 30 to 35 per cent of
      cases. Endoscopic stenting effectively relieves jaundice and can provide long
      term palliation comparable with surgical bypass; 12 of 29 patients in our
      endoscopic group survived 12 months or longer, and one is alive at 84 months
      after initial stenting.

PMID- 10966024
TI  - Isolated small gallbladder polyps: an indication for cholecystectomy in
      symptomatic patients.
AB  - To evaluate patients with gallbladder polyps and to compare them with patients
      with chronic acalculous cholecystitis, 301 patients with chronic acalculous
      disease of the gallbladder, of which 45 had polyp disease of the gallbladder,
      were reviewed out of 7181 cholecystectomies performed from June 1985 through June
      1995. Of the 45 patients, 30 (Group A) were diagnosed preoperatively by
      ultrasound and 15 (Group B) postoperatively on pathologic examination. In each
      group, the most common polyp was cholesterol type (19/45) with multiple lesions
      in 10 of these 19 patients. Chronic cholecystitis was present elsewhere in the
      gallbladder in 40 per cent of Group A and 80 per cent of Group B patients (P =
      0.02). Forty-three patients had polyps less than 5 mm in diameter, one a 1.5-cm
      gallbladder cholesterol polyp, and one a 1.3-cm tubulovillous polyp with a focus
      of carcinoma in situ. During this same period, 17 patients had primary malignancy
      of the gallbladder, none of which were found in polypoid lesions. In Group A
      patients there were significantly fewer preoperative tests than in typical
      acalculous patients [2.3 versus 3.8 (P<0.03)], including upper endoscopy (P<0.02)
      and hepatobiliary scintigraphy (P<0.00001). Of the patients with polyps, 42 of 45
      (93.3%) had resolution of symptoms postoperatively with a mean follow-up of
      178.9+/-505.0 days (range 1-2438 days). Most patients with biliary tract symptoms
      and a small (<5-mm) gallbladder polyp underwent fewer preoperative diagnostic
      tests than patients with chronic acalculous cholecystitis. This abbreviated
      preoperative workup appears warranted in view of the high incidence of symptom
      resolution.

PMID- 10966025
TI  - Traumatic hemorrhage of occult pheochromocytoma: a case report and review of the
      literature.
AB  - Pheochromocytoma usually presents with gradual onset and mild to moderate
      symptoms, but may present acutely with severe symptoms. Hemorrhage into
      pheochromocytoma is a rare cause of acute presentation that is often devastating
      to patients. We describe the case of a 34-year-old woman with hemorrhage into a
      previously undiscovered pheochromocytoma following a fall on a patch of ice. This
      is the first reported case of hemorrhagic pheochromocytoma associated with
      traumatic injury. Despite removal of the tumor within 18 hours of presentation,
      the patient suffered severe complications of massive catecholamine excess,
      including shock, cardiomyopathy, and adult respiratory distress syndrome. Animal
      studies have shown that early treatment with alpha blockers can prevent some, if
      not all of these complications. Proper management of hemorrhagic pheochromocytoma
      should include a high index of suspicion with early diagnosis and treatment with
      alpha blockers and surgical resection of the tumor when the patient is stable
      enough to tolerate the procedure.

PMID- 10966026
TI  - Right lower quadrant abdominal pain due to appendicitis and an incarcerated
      spigelian hernia.
AB  - Spigelian hernias are uncommon and difficult to diagnose because of their
      location in the aponeurosis in the anterior abdominal wall. When they occur on
      the right side, the symptoms can include nonspecific abdominal pain mimicking
      appendicitis. We present an adult with right lower quadrant abdominal pain due to
      an incarcerated spigelian hernia and acute appendicitis. Early recognition and
      prompt surgical treatment were important to the successful treatment of our
      patient.

PMID- 10966027
TI  - Surgical repair of inguinal hernia: tension free technique with prosthetic
      materials (Gore-Tex Mycro Mesh expanded polytetrafluoroethylene).
AB  - The purpose of this study is to report the results of a tension-free repair
      technique using expanded polytetrafluoroethylene Gore-Tex Mycro Mesh in patients
      with inguinal hernias. Over 3 years, 104 patients have undergone the
      aforementioned procedure for 118 hernias (85 indirect and 33 direct) in our
      clinic. Ninety-three of the patients were operated for the first time, whereas
      the remainder of them were operated for hernia recurrence. Fourteen patients had
      bilateral hernias, and six had incarcerated ones. The median patient's age was 53
      years. Eighty-three patients were operated under general and 21 under local or
      epidural anesthesia. One hundred and two patients were offered a one-day surgery
      procedure, but three were readmitted with wound infection. Two of these patients
      were conservatively cured, and the third was submitted to mesh removal. Two
      patients developed hematoma in the scrotum and were discharged a week later after
      the absorption of the hematoma. All of the patients except the one who was
      submitted to mesh removal returned to normal life within a week after the
      operation. During the follow-up period, none of our patients experienced hernia
      recurrence. Our results are in accordance with those of the world literature. We
      perform the tension-free hernia repair by using the expanded
      polytetrafluoroethylene mesh in our patients because we believe it is a safe
      procedure without significant postoperative morbidity and with no hernia
      recurrences.

PMID- 10966028
TI  - Pancreaticoduodenectomy for lymphoepithelial cyst of the pancreas.
AB  - Lymphoepithelial tumors of the pancreas are rare cystic tumors characterized by
      the presence of a keratinizing squamous epithelium and a dense lymphoid
      infiltrate on histologic examination. This case report describes the first
      lymphoepithelial tumor to be resected from the pancreatic head by
      pancreaticoduodenectomy. This case is also the first in which the cyst was found
      to be secondarily infected. The radiologic and clinicopathologic features of
      these unusual tumors are discussed.

PMID- 10966029
TI  - Management guidelines for hypotensive pelvic fracture patients.
AB  - Pelvic fractures are common in blunt trauma patients and are often associated
      with other system injuries. Most studies describe the type of pelvic fractures
      and classify them by the forces creating the injury. Mortality from these
      fractures is due most often to other system injuries or to hemorrhage. Mortality
      ranges from 5 to 20 per cent depending on complexity and number of systems
      injured. We studied 692 cases of pelvic fractures and analyzed the seriously ill
      patients. They were identified by blood pressure (BP) less than 90 systolic on
      presentation to the trauma room and having a complex pelvic fracture. The
      management of these patients was by a protocol used by a group of eight trauma
      surgeons. This group of 75 hypotensive pelvic fracture patients were analyzed to
      identify significant factors in their management that predicted mortality.
      Patients with base excess (BE) values < or =-5 were significantly more likely to
      die (P<0.05). Patients with BP < or =90 on leaving the trauma room had a
      significantly higher mortality (P<0.01). Injury Severity Score predicted
      mortality and can be useful as a tool for quality assurance and process
      improvement. The early operative intervention to fix associated fractures within
      24 hours was not detrimental to patient outcome. Overall mortality in this very
      sick population was 14.7 per cent. Emergent angiography was used successfully on
      14 patients. Seven patients died of continued bleeding. The most important
      management guidelines for these seriously injured, complex patients are: 1)
      resuscitate with BE used as a monitor; 2) keep patient blood volume as close to
      normal as possible; 3) use BP, BE, and ISS to evaluate management of these
      patients.

PMID- 10966030
TI  - Stump appendicitis.
AB  - There has been a recent increase in interest in stump appendicitis with the rapid
      development of laparoscopic appendectomy. The objective of this study is to
      determine the frequency, management, and prevention of stump appendicitis in a
      retrospective review of 2185 cases of appendectomy and right colectomy at the
      Massachusetts General Hospital from 1960 to 1998. Three patients with stump
      appendicitis were identified. Patients presented with epigastric or periumbilical
      pain that radiated to the right lower quadrant. All had focal abdominal signs and
      a mild to moderate leukocytosis, and all underwent right colectomy. Pathology
      noted appendiceal stumps 5 mm deep. Two additional patients with chronic
      abdominal pain had cecal filling defects on barium enema. Endoscopically, these
      appendiceal stumps were 7 mm deep with impacted fecaliths and pathologic changes
      consistent with early inflammation. The stumps were resected by snare
      electrocautery. Stump appendicitis is a very rare entity. Its incidence may be
      minimized with accurate visualization of the appendiceal base and creation of an
      appendiceal stump less than 3 mm in depth. There is no correlation between simple
      ligation or inversion of the stump and stump appendicitis. There should not be a
      sudden increase in the incidence of this entity if laparoscopic appendectomy is
      performed properly.

PMID- 10966031
TI  - Controversy in the treatment of adult long ileocolic intussusception: case
      report.
AB  - Adult intussusception is an unusual cause of intestinal obstruction. In contrast
      to children, intussusception in adults is usually due to an identifiable cause.
      We present a case of an 81-year-old female who was diagnosed with a long
      intussusception on CT scan of the abdomen. Because of the likelihood of
      neoplasia, a right hemicolectomy was undertaken, after which the patient
      recovered well. The correct treatment of adult intussusception is not unanimously
      agreed upon. We present a case of long intussusception in which partial reduction
      of viable small bowel before the resection was done by applying gentle traction.
      This provided sufficient small bowel mesentery length, preventing any damage to
      superior mesenteric vessels and avoiding unnecessary excision of healthy bowel.

PMID- 10966032
TI  - Mammographic considerations for patients undergoing ancillary surgical procedures
      in the breast: a need for pre- and postoperative mammograms.
AB  - Mammographic evaluation of the pre- and postoperative breast has been primarily
      emphasized for patients undergoing diagnostic breast biopsies and breast
      conserving surgery. There is limited literature addressing ancillary surgical
      procedures involving breast tissue that may complicate mammographic evaluation of
      the breasts during breast cancer screening. We present mammographic diagnostic
      dilemmas after ancillary surgical procedures in the breast. The placement and
      removal of devices, such as central venous access ports and pacemakers, may
      result in scarring that may appear suspicious for malignancy on mammography. In
      addition, the placement of devices can obscure lesions that are being followed
      mammographically. These cases illustrate the need for the application of a basic
      principle of breast surgery, that of pre- and postoperative mammography, to
      ancillary surgery of the breast to allow optimal mammographic evaluation of women
      who are breast screening candidates.

PMID- 10966033
TI  - The antiphospholipid symdrome in a teenage with miscarriages, thromboses, and
      diabetes mellitus.
AB  - The antiphospholipid syndrome has been associated with many clinical conditions
      since its description by GRV Hughes in 1983. The linkage to Type 1 diabetes
      mellitus has not been established. There have been no reports of deep venous
      thrombosis in association with antiphospholipid syndrome and diabetes mellitus.
      We present the case of an African-American teenager with multiple miscarriages,
      diabetic ketoacidosis, deep venous thromboses, and elevated immunoglobulin M and
      G anticardiolipin antibodies. We urge that clinicians consider testing for
      antiphospholipid antibodies when diabetic patients present with multiple
      miscarriages or deep venous thrombosis.

PMID- 10966034
TI  - Postoperative suppressive therapy for thyroid adenomas.
AB  - Thyroid adenoma is a common disease. If partial thyroidectomy is performed,
      postoperative suppression therapy is often given to avoid nodule development in
      the remaining thyroid. It is unclear whether this treatment is warranted.
      Patients who underwent a partial thyroidectomy with a histologic diagnosis of
      follicular thyroid adenoma from January 1985 until February 1998 were studied
      retrospectively. Patients were analyzed on the basis of postoperative therapy,
      new thyroid nodule growth, and costs. Seventy-six patients were identified with a
      recurrence rate of 4 per cent (3/76). Sixty-one per cent (46/76) were treated
      with postoperative thyroid suppression therapy, and no difference in new nodule
      development was noted with at least 6 months of follow-up (P = 0.274). No
      patients required reoperation. A large cost saving was shown for patients who
      were not treated with levothyroxine. We conclude that postoperative thyroid
      suppression may not be routinely indicated. A prospective, randomized study would
      be necessary to answer this question conclusively.

PMID- 10966035
TI  - Transient Horner's syndrome in a trauma patient with thoracic epidural analgesia:
      a case report.
AB  - Homer's syndrome, which classically presents as ipsilateral ptosis, meiosis, and
      facial anhydrosis, may present as a consequence of thoracic epidural analgesia.
      Pain that limits the patient's ability to maintain adequate pulmonary mechanics
      may optimally be treated with a thoracic epidural. The importance of recognition
      of a Horner's syndrome in such a patient is critical in preventing unnecessary
      anxiety for the patient and potentially embarking on an unnecessary diagnostic
      workup. The following is a case presentation of a patient who sustained multiple
      rib fractures in an automobile accident. The patient presented with a Horner's
      syndrome after a thoracic epidural infusion had begun. This article highlights
      the importance of early recognition of this benign, transient syndrome and
      discusses the pathways and potential mechanism of this process.

PMID- 10966036
TI  - The use of the Valtrac ring in the upper and lower gastrointestinal tract, for
      single, double, and triple anastomoses: a report of 50 cases.
AB  - The Valtrac biofragmentable anastomotic ring (V-BAR) technique has been widely
      used in clinical practice, particularly in anastomoses of the colon. The success
      of this method encouraged some surgeons to use it also in anastomosis of the
      small intestine. We are convinced that the method can be used successfully also
      in anastomosis of the small intestine and the upper gastrointestinal tract,
      particularly in cases of technically difficult and high-risk anastomoses. Between
      1995 and 1998, we used the V-BAR in 35 patients, performing a total of 50
      anastomoses. In 13 patients a double anastomosis was created in the same
      operation, and in one patient a triple anastomosis was created. In all we
      performed one end-to-end esophagojejunostomy, one gastrojejunostomy, six
      gastroileostomies, two duodenojejunal anastomoses, 13 end-to-end
      duodenoileostomies, one jejuno-jejunal anastomosis, 18 end-to-side ileoileal
      anastomoses, one ileocolic anastomosis, and seven colocolic anastomoses. Follow
      up at between 2 and 36 months showed good overall results with regard to
      resumption of intestinal transit and canalization, even in those cases in which a
      double and triple suture was performed using the Valtrac ring. In our experience,
      the V-BAR can be used in upper gastrointestinal surgery with excellent results.
      Compared with manual sutures, the ring allows better and faster resumption of
      transit and canalization.

PMID- 10966037
TI  - Surgical management of malignant melanoma using dynamic lymphoscintigraphy and
      gamma probe-guided sentinel lymph node biopsy: the Emory experience.
AB  - Sentinel lymph node (SLN) biopsy is revolutionizing the surgical management of
      primary malignant melanoma. It allows accurate nodal staging which targets
      patients who may benefit from regional lymphadenectomy and systemic therapy. This
      is a retrospective review of patients treated at Emory University for stage I and
      II malignant melanoma with gamma probe-guided SLN biopsy from 1/1/94 to 6/30/98.
      Three hundred sixty patients (males 228, females 132) were identified. Primary
      melanoma sites included: head and neck 58, trunk 148, and extremities 154 (upper
      71, lower 83). Primary tumor staging was T1 9, T2 134, T3 153, and T4 64. SLNs
      were successfully identified in 99.7 per cent of patients and 98.9 per cent of
      nodal basins mapped. In 275 (76.6%) cases a single draining nodal basin was
      identified. In 84 (23.3%) cases there were multiple draining nodal basins.
      Positive SLNs were identified in 63 patients (17.5%). SLN positivity by tumor
      staging was T1 0 per cent, T2 9.0 per cent, T3 22.2 per cent, and T4 26.6 per
      cent. The overall recurrence rate was 11.9 per cent. Recurrences by SLN status
      were SLN+, 27 per cent, and SLN-, 8.8 per cent. Regional recurrence occurred in 7
      (2.4%) of the 297 with negative SLN biopsies and 7 (11.1%) of the 63 with
      positive SLN biopsies. Dynamic lymphoscintigraphy and gamma probe-guided SLN
      localization was successful in more than 98 per cent of cases. Patients with
      negative SLN biopsies have a low risk of recurrence.

PMID- 10966038
TI  - Concomitant renal revascularization with aortic surgery: are the risks of
      combined procedures justified?
AB  - Indications for concomitant renal revascularization during aortic surgery are not
      well established. Higher mortality and poorer results are often cited. To examine
      this, all combined aortic and renal revascularization procedures from August 1992
      until May 1998 were reviewed. Of 2003 major arterial reconstructions performed on
      the Vascular Teaching Service, 45 patients (2%) underwent renal
      revascularization. Of these 31 patients (69%) had combined aortic and renal
      procedures. Aortic pathology in these 31 patients (54% male, 94% white, median
      age 64 years) included arterial occlusive disease (n = 21; 47%), abdominal aortic
      aneurysm (n = 6; 13%), and thoracoabdominal aortic aneurysm (n = 4; 9%). In all
      31 cases the patient presented because of the aortic pathology. Indications for
      concomitant renal revascularization included renovascular hypertension (n = 21;
      68%) and preservation of renal function (n = 10; 32%). Renal revascularization
      procedures included transaortic endarterectomy (n = 23; 74%), renal bypass (n =
      7; 23%), and both bypass and endarterectomy (n = 1; 3%). Seven (22%)
      complications and two (6%) deaths (both patients operated on for renal salvage)
      occurred perioperatively. Complications included wound infection (n = 2; 6%),
      postoperative bleeding (n = 1; 3%), respiratory failure (n = 1; 3%), deep venous
      thrombosis (n = 1; 3%), cerebrovascular accident (n = 1; 3%), and
      pseudomembranous enterocolitis (n = 1; 3%). All patients either were cured of
      their hypertension (n = 5; 24%) or were improved (n = 16; 76%) at 3 months. No
      patient to date operated on for renal salvage progressed to chronic hemodialysis,
      but mortality was higher after renal revascularization for renal salvage versus
      hypertension (20% vs. 0; P = 0.034). There was no significant difference in
      mortality between the combined aortic/renal procedures versus aortic procedures
      alone. Despite adding complexity, renal revascularization in patients undergoing
      aortic surgery appears relatively safe and effective. These data favor an
      aggressive approach toward renal revascularization in selected patients needing
      aortic surgery.

PMID- 10966039
TI  - Carotid endarterectomy reoperations in a regional medical center.
AB  - Large, randomized prospective clinical trials have not addressed the safety of
      reoperation for recurrent carotid disease. Our purpose was to determine whether
      outcomes for carotid endarterectomy for recurrent disease were different from
      those for primary or contralateral carotid endarterectomy. We reviewed all
      carotid endarterectomies done in our regional medical center hospital from 1979
      through 1997. We analyzed 1656 primary procedures, 377 contralateral carotid
      procedures, and 63 reoperations. Operation for recurrent disease was done in 3
      per cent of those having primary operations. Patients in the three groups did not
      differ significantly with regard to age, race, or sex. Seventy per cent of
      patients were symptomatic with transient ischemic attacks, amaurosis, and
      reversible ischemic neurological deficit being most prominent. There were no
      deaths and three strokes in the reoperation group for a combined stroke and death
      rate of 4.8 per cent. This was not significantly different from that of 3.2 per
      cent for the stroke and death rate for the primary group and 3.5 per cent for the
      contralateral group. Carotid endarterectomy is a safe treatment for recurrent
      carotid artery disease.

PMID- 10966040
TI  - Supervised training of general surgery residents in carotid endarterectomy
      performed on awake patients under regional block is safe and desirable.
AB  - Previous studies have documented the safety and efficacy of general surgery
      residents and vascular fellows performing carotid endarterectomy (CEA) under the
      supervision of an attending surgeon. With the proper supervision of the attending
      surgeon, these operations can be performed with an acceptably low perioperative
      stroke and mortality rate. The question remains, however, whether these desirable
      results can be obtained by general surgery residents when operating on awake
      patients under regional block (RB) anesthesia. We set out to determine whether it
      is prudent to promote this technique in this teaching setting. We analyzed 128
      CEAs performed at a community teaching hospital training three chief residents a
      year. These operations were performed by residents under the direct supervision
      of a single attending vascular surgeon. RB was preferred and was used in 67
      operations. General anesthesia (GA) was used in the remaining 61 procedures.
      Overall mortality was 0 per cent. Patients in the RB group were converted
      intraoperatively to GA in 4 of 67 (6%) procedures. There was one perioperative
      stroke in this series (1/128, 0.78%), occurring in a patient under RB (1/67, 1.5
      %) leaving the patient with a minor sensory deficit. No strokes occurred in the
      GA group. There were five temporary cranial nerve deficits (3.9%). Three were in
      the RB group (4.5%) and two in the GA group (3.3%). General surgery residents can
      be trained in the performance of carotid endarterectomy using regional block
      anesthesia in awake patients without compromising patient safety. Suggestions to
      the effect that only attending physicians and/or vascular fellows can perform
      these procedures under regional block are without merit.

PMID- 10966041
TI  - Axillary hibernoma: an unusual soft tissue tumor.
AB  - Hibernomas are rare soft tissue tumors of brown fat differentiation. A case of a
      large axillary hibernoma, along with a review of its pathology, is presented.
      This tumor matches the largest hibernoma in the literature and is the largest in
      an axillary site.

PMID- 10966042
TI  - Adenocarcinoma in a hemorrhoidectomy specimen: case report and review of the
      literature.
AB  - Our purpose is to report a case of unexpected anal adenocarcinoma found in a
      hemorrhoidectomy specimen. A review of the literature, with emphasis on
      extramucosal anal adenocarcinoma as a pathologic entity, is included. Our patient
      presented with a 2-year history of grade III prolapsing internal hemorrhoids. A
      hemorrhoidectomy was performed and gross examination of the specimen was
      unremarkable. The pathologic evaluation revealed microinvasive well
      differentiated adenocarcinoma at the squamocolumnar junction. There was neither
      an apparent connection with the overlying mucosa nor an in situ component. A
      metastatic workup ruled out any other site of malignancy. At follow-up 18 months
      after surgery, no evidence of malignancy or recurrence was observed. An
      unexpected extramucosal anal adenocarcinoma in a hemorrhoidectomy specimen is a
      very exceptional finding. Review of the literature does not support routine
      histopathological examination of hemorrhoidectomy specimens.

PMID- 10966043
TI  - Left-side preference in carotid endarterectomies.
AB  - Although the incidence of carotid atheromatous disease is presumably equal
      between the right and left carotid arteries, right and left carotid
      endarterectomies (CEs) may not be performed with equal frequency on the two
      sides. This study sought to examine whether right and left CEs are performed with
      equal frequency and whether there are any differences in outcome between these
      groups. Detailed chart review was performed on all CEs performed from 1979
      through 1998 at our institution, and those lacking side data were excluded. Data
      were collected on the side of the procedure, demographics, comorbid conditions,
      details of the procedure, hospital stay, and major complications. The surgeons
      performing CE were surveyed about their practice of considering side factors. CE
      was performed on the left in 1190 (52%) of 2305 procedures; 1115 (48%) of the
      procedures were right CEs. This difference is statistically significant (P =
      0.014). No significant differences in demographics, comorbidity, presence of
      symptoms before surgery, length of stay, or postoperative morbidity or mortality
      between the left and right groups were found. A majority of the surgeons surveyed
      indicated they do consider the relationship of side of the carotid disease to the
      patient's dominant side. The significant difference in the performance of left CE
      more often than right has not been previously reported. This may reflect
      willingness by surgeons to intervene more frequently in carotid disease on the
      side supplying the dominant hemisphere. A prospective CE outcome study that
      identifies the side of CE and the patient's dominant side is needed for further
      exploration of this issue.

PMID- 10966044
TI  - Enoxaparin associated with hugh abdominal wall hematomas: a report of two cases.
AB  - Enoxaparin is a low-molecular-weight heparin used for prophylaxis against deep
      venous thrombosis. Indications include hip and knee replacement surgery, risk of
      deep venous thrombosis during abdominal surgery, and prevention of ischemic
      complications of unstable angina and non-Q-wave myocardial infarction. Its
      efficacy in the prevention of the above complications has been previously
      studied; however, the liberal use of enoxaparin is not without incident.
      Complications of enoxaparin include hemorrhage, thrombocytopenia, and local
      reactions. Since 1993 there have been more than 40 reports of epidural or spinal
      hematoma formation with the concurrent use of enoxaparin and spinal/epidural
      anesthesia or spinal puncture. Herein reported are two cases of abdominal wall
      hematomas in patients receiving prophylaxis with enoxaparin. Both patients
      sustained an unexplained fall in the hematocrit and abdominal pain. A CT scan
      confirmed the diagnosis. One patient recovered uneventfully; however, the other
      patient, on chronic hemodialysis, became hemodynamically unstable and
      hyperkalemic and sustained a fatal cardiac arrhythmia. An extensive review of the
      literature revealed no similar cases of abdominal wall hematomas associated with
      enoxaparin although other complications, including spinal and epidural hematomas,
      psoas hematomas, and skin necrosis have been reported. The extended use of
      enoxaparin as an anticoagulant requires the physician to be vigilant of these
      rare complications. Bleeding can occur at any site during therapy with
      enoxaparin. An unexplained fall in the hematocrit or blood pressure should lead
      to a search for a bleeding site.

PMID- 10966045
TI  - Harvey Cushing: a historical vignette.

PMID- 10966046
TI  - Re: Are CXRs mandatory following central venous recatheterization over a wire?

PMID- 10966047
TI  - Galen's life and contributions.

PMID- 10966048
TI  - Effect of imbalance in activities between ON- and OFF-center LGN cells on
      orientation map formation.
AB  - It has been reported that the OFF responses of cells in the visual pathway are
      stronger, on average, than the ON responses early in the life of cats and
      ferrets. In this study, we theoretically investigate the effects of this
      imbalance in activity on the orientation map formation. We carry out computer
      simulations based on our previously proposed self-organization model, in which
      the correlated activities between ON- and OFF-center cells in the lateral
      geniculate nucleus regulate the formation of orientation maps in the visual
      cortex. When imbalance between the activities of these ON- and OFF-center cells
      is assumed, we obtain orientation maps with spatial periodicity, as observed in
      the experiments. On the other hand, when balanced activities are assumed,
      orientation maps do not show periodicity. This suggests that the imbalance in
      activities between ON- and OFF-center cells contributes to the elaboration of
      orientation maps during the critical period.

PMID- 10966049
TI  - A Brownian simulation model of glutamate synaptic diffusion in the femtosecond
      time scale.
AB  - To gain a better understanding of the elementary unit of synaptic communication
      between hippocampal neurons, we simulated the release of glutamate from a single
      pre-synaptic vesicle and its diffusion into the synaptic cleft. Diffusion of
      glutamate was simulated by a Brownian model based on Langevin equations. The
      model was implemented for parallel computer simulation and tested under different
      conditions of glutamate release and different geometrical and physical
      characteristics of the synaptic cleft. All the tested parameters have shown to be
      important for the synaptic responses. The results show that the synaptic
      transmission efficacy is influenced by many different geometrical parameters and,
      as a consequence, the quality of the excitatory postsynaptic response can be very
      different in the same synapse. The variability in the quantal response found by
      several authors can also be explained by physical parameters other than by
      variations in the quantal content of the synaptic vesicle as proposed by these
      authors.

PMID- 10966050
TI  - Properties of basis functions generated by shift invariant sparse representations
      of natural images.
AB  - The idea that a sparse representation is the computational principle of visual
      systems has been supported by Olshausen and Field [Nature (1996) 381: 607-609]
      and many other studies. On the other hand neurons in the inferotemporal cortex
      respond to moderately complex features called icon alphabets, and such neurons
      respond invariantly to the stimulus position. To incorporate this property into
      sparse representation, an algorithm is proposed that trains basis functions using
      sparse representations with shift invariance. Shift invariance means that basis
      functions are allowed to move on image data and that coefficients are equipped
      with shift invariance. The algorithm is applied to natural images. It is
      ascertained that moderately complex graphical features emerge that are not as
      simple as Gabor filters and not as complex as real objects. Shift invariance and
      moderately complex features correspond to the property of icon alphabets. The
      results show that there is another connection between visual information
      processing and sparse representations.

PMID- 10966051
TI  - Statistical independence and neural computation in the leech ganglion.
AB  - In this report, the input/output relations in an isolated ganglion of the leech
      Hirudo medicinalis were studied by simultaneously using six or eight suction
      pipettes and two intracellular electrodes. Sensory input was mimicked by
      eliciting action potentials in mechanosensory neurons with intracellular
      electrodes. The integrated neural output was measured by recording extracellular
      voltage signals with pipettes sucking the roots and the connectives. A single
      evoked action potential activated electrical activity in at least a dozen
      different neurons, some of which were identified. This electrical activity was
      characterized by a high degree of temporal and spatial variability. The action
      potentials of coactivated neurons, i.e. activated by the same mechanosensory
      neuron, did not show any significant pairwise correlation. Indeed, the analysis
      of evoked action potentials indicates clear statistical independence among
      coactivated neurons, presumably originating from the independence of synaptic
      transmission at distinct synapses. This statistical independence may be used to
      increase reliability when neuronal activity is averaged or pooled. It is
      suggested that statistical independence among coactivated neurons may be a usual
      property of distributed processing of neuronal networks and a basic feature of
      neural computation.

PMID- 10966052
TI  - The prediction of EEG signals using a feedback-structured adaptive rational
      function filter.
AB  - In this article, we present a feedback-structured adaptive rational function
      filter based on a recursive modified Gram-Schmidt algorithm and apply it to the
      prediction of an EEG signal that has nonlinear and nonstationary characteristics.
      For the evaluation of the prediction performance, the proposed filter is compared
      with other methods, where a single-step prediction and a multi-step prediction
      are considered for a short-term prediction, and the prediction performance is
      assessed in normalized mean square error. The experimental results show that the
      proposed filter shows better performance than other methods considered for the
      short-term prediction of EEG signals.

PMID- 10966053
TI  - Self-organized dynamics in plastic neural networks: bistability and coherence.
AB  - In this paper, we study the combined dynamics of the neural activity and the
      synaptic efficiency changes in a fully connected network of biologically
      realistic neurons with simple synaptic plasticity dynamics including both
      potentiation and depression. Using a mean-field of technique, we analyzed the
      equilibrium states of neural networks with dynamic synaptic connections and found
      a class of bistable networks. For this class of networks, one of the stable
      equilibrium states shows strong connectivity and coherent responses to external
      input. In the other stable equilibrium, the network is loosely connected and
      responds non coherently to external input. Transitions between the two states can
      be achieved by positively or negatively correlated external inputs. Such networks
      can therefore switch between their phases according to the statistical properties
      of the external input. Non-coherent input can only "rcad" the state of the
      network, while a correlated one can change its state. We speculate that this
      property, specific for plastic neural networks, can give a clue to understand
      fully unsupervised learning models.

PMID- 10966054
TI  - Identification of the cable parameters in the somatic shunt model.
AB  - We show that the first five moments of the soma potential and soma current
      uniquely and stably determine the soma conductance and capacitance and the
      dendritic electrotonic length, conductance, and capacitance in the so-called
      somatic shunt model of the passive behavior of a neuron. We test our resulting
      input admittance algorithm on synthetic data and demonstrate the regularizing
      effect of knowledge of the ratio of soma to dendrite surface areas.

PMID- 10966055
TI  - Different effects of blocked potassium channels on action potentials,
      accommodation, adaptation and anode break excitation in human motor and sensory
      myelinated nerve fibres: computer simulations.
AB  - Action potentials and electrotonic responses to 300-ms depolarizing and
      hyperpolarizing currents for human motor and sensory myelinated nerve fibres have
      been simulated on the basis of double cable models. The effects of blocked nodal
      or internodal potassium (fast or slow) channels on the fibre action potentials,
      early and late adaptations to 30-ms suprathreshold slowly increasing depolarizing
      stimuli have been examined. The effects of the same channels on accommodation
      after the termination of a prolonged (100 ms) hyperpolarizing current pulse have
      also been investigated. By removing the nodal fast potassium conductance the
      action potentials of the sensory fibres are considerably broader than those of
      the motor neurons. For both types of fibres, the blocked nodal slow potassium
      channels have a substantially smaller effect on the action potential
      repolarization. When the suprathreshold depolarizing current intensity is
      increased, the onset of the spike burst occurs sooner, which is common in the
      behaviour of the fibres. The most striking differences in the burst activity
      during early adaptation have been found between the fibres when the nodal fist
      potassium channels are blocked. The results obtained confirm the fact that the
      motor fibres adapt more quickly to sustained depolarizing current pulses than the
      sensory ones. The results also show that normal human motor and sensory fibres
      cannot be excited by a 100-ms hyperpolarizing current pulse, even at the
      threshold level. When removing the potassium channels in the nodal or internodal
      axolemma, the posthyperpolarization increase in excitability is small, which is
      common in the behaviour of the fibres. However, anode break excitation can be
      simulated in the fibres with simultaneous removal of the potassium channels under
      the myelin sheath, and this is more pronounced in the human sensory fibres than
      in motor fibres. This phenomenon can also be found when the internodal and some
      of the nodal (fast or slow) potassium channels are simultaneously blocked.

PMID- 10966056
TI  - Induction of tumor peptide-specific cytotoxic T cells under serum-free conditions
      by mature human dendritic cells.
AB  - Tumor vaccination strategies using antigen-pulsed dendritic cells (DC) are
      currently under development. We established an in vitro system using cultured DC
      from HLA-typed volunteers for the induction of tumor peptide-specific CD8+ T
      cells. The strength and specificity of the resulting CTL responses were
      investigated. For stimulation of syngeneic CD8+ T cells two well-defined DC
      populations were generated: CD1a+ immature DC cultured in the presence of GM-CSF
      and IL-4 and mature CD83+ DC generated by additional stimulation with a cytokine
      cocktail. Stimulations were performed under serum-free conditions and in the
      absence of exogenous cytokines. Analysis of T cell responses showed that mature
      DC, but not immature DC, were able to induce the expansion of syngeneic tumor
      peptide-specific CD8+ T cells. Priming of CD8+ T cells with peptide-pulsed mature
      DC rapidly increased the frequency of antigen-specific T cells (ELISPOT
      technique). T cells induced by mature DC showed strong antigen-specific
      cytotoxicity in 51Cr-release assays whereas no antigen-specific cytotoxicity was
      detectable in CTL generated by immature DC. These data show that terminally
      differentiated mature DC are necessary for the induction of tumor antigen
      specific CTL responses.

PMID- 10966058
TI  - Chemokine release from activated human dermal microvascular endothelial cells-
      implications for the pathophysiology of scleroderma?
AB  - Long-term exposure to silica (SiO2) may induce silicosis as well as
      extrapulmonary diseases such as scleroderma. Infiltration of mononuclear cells
      and release of proinflammatory cytokines from these cells have been suggested to
      play a role in the development of inflammatory and immunological events typical
      of scleroderma as well as of silica-induced scleroderma. We showed that silica is
      able to directly activate cytokine expression in blood monocytes, collagenase
      expression in cultured dermal fibroblasts and ICAM-1 expression in human dermal
      microvascular endothelial cells. In the study reported here we found that silica
      and TNFalpha induce mRNA and protein of the chemokines RANTES and MCP-1 in
      endothelial cells. In addition, we demonstrated that culture supernatants of
      silica-treated endothelial cells are chemotactic for mononuclear cells from
      peripheral blood, suggesting that activation of endothelial cells may contribute
      to the chemotactic gradient necessary for extravasation of inflammatory blood
      cells into the surrounding tissue found in early scleroderma. However, a
      polyclonal anti-RANTES antibody failed to block chemotaxis suggesting that other
      proteins are involved in this phenomenon. We also studied the expression of
      RANTES in situ in the skin of systemic sclerosis patients and of healthy
      individuals. We found abundant RANTES mRNA expression in the skin of SSc
      patients, whereas in control skin no expression was found. From our data we
      conclude that RANTES and MCP-1 induction by silica may be an initiating event in
      inflammatory infiltration, whereas TNFalpha-mediated inflammation may propagate
      the disease more efficiently.

PMID- 10966057
TI  - Release of histamine and leukotriene C4 in immediate allergic wheal reaction as
      measured with the microdialysis technique.
AB  - Other mediators as well as histamine can contribute to the allergic wheal
      reaction. In this study, the microdialysis technique was used to monitor the
      release of histamine, leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in prick
      test wheal reactions induced by cow dander allergen. Of 31 atopic subjects, 25
      showed detectable histamine release that correlated significantly with the number
      of tryptase-positive mast cells and serum cow-specific IgE but not with the wheal
      size. Detectable LTC4 release was shown by 16 of 18 subjects, but PGD2 release
      was shown by only 7 of 17 subjects, and neither mediator was associated with
      tryptase-positive mast cells, IgE levels or wheal size. An inverse association
      between histamine release and LTC4 release in these 18 subjects was found rather
      than a direct correlation. With advancing age of the subject histamine release (n
      = 31) tended to decrease, although insignificantly, but LTC4 release (n = 18) and
      sensitivity to histamine prick increased significantly, which seemed to parallel
      the changes in the wheal size induced by cow allergen. In conclusion, the results
      showed that the release of histamine, LTC4 or PGD2 alone cannot explain the
      extent of the wheal reaction. In addition, the amount of histamine released was
      not related to the amount of LTC4 released, but rather an inverse association
      existed between these mediators.

PMID- 10966059
TI  - Effects of whole-body UVB irradiation on cytokine production by peripheral blood
      mononuclear cells from stage I melanoma patients.
AB  - Ultraviolet (UV) radiation causes significant impairment of immunological
      function in human skin. The immunosuppressive effects of UV radiation are thought
      to be due to local release of cytokines by human keratinocytes, leading to
      impaired function of epidermal antigen-presenting cells (APC) and failure to
      induce cutaneous delayed-type hypersensitivity (DTH) reactions. Recent studies
      have shown that individuals susceptible to UV-induced suppression of DTH may be
      more prone to develop skin cancer including malignant melanoma (MM). Since the
      causal relationship between UV radiation and the induction of MM still seems
      obscure, we investigated the immunological reactions of peripheral blood
      mononuclear cells (PBMC) to whole-body irradiation with UVB in 15 stage I
      melanoma patients as compared to PBMC from normal volunteers matched for age,
      gender and skin type. Whole-body irradiation was performed with 0.8 minimal
      erythema dosages on five consecutive days. Peripheral blood was obtained before
      and after the procedure. Overall, there were no major effects of UVB irradiation
      on peripheral lymphocyte subsets and proliferation of PBMC from patients or
      normal controls, but UVB irradiation led to a significant increase in PWM
      stimulated production of IL-6, IL-2R and TNF by PBMC. These changes were
      independent of the individual UVB dosages administered and appeared in both
      groups similarly. UVB irradiation did not lead to significant changes on IL-1 and
      IL-2 expression by PBMC. Our results suggest that PBMC participate in the
      cytokine response to UV, even in the absence of inflammatory reactions, but that
      this participation is not specific to MM patients.

PMID- 10966060
TI  - Expression and activity of P-glycoprotein in transplantable hamster melanomas.
AB  - In the study described here we investigated the possibility of an association
      between the aggressiveness of melanoma and multidrug resistance phenotype by
      analyzing the expression and activity of P-glycoprotein (Pgp) in two genetically
      related transplantable hamster melanomas--a melanotic (Ma) and an amelanotic (Ab)
      form --which differed in aggressiveness and metastatic potential. Flow cytometric
      analysis of Pgp activity (using a verapamil-sensitive rhodamine R123 exclusion
      test) as well as Western blotting of cellular lysates showed its preferential
      (although not very marked) expression in the Ab melanoma cells. The Ab melanoma
      cells also exhibited a higher proportion of tumor-infiltrating lymphocytes (TIL),
      mostly of T cell phenotype, that may have reflected a higher immunogenicity of
      the tumor. In conclusion, Pgp activity appeared to be associated with less
      differentiated more aggressively metastasizing melanoma (the Ab variant) although
      its role in maintaining this phenotype remains to be established.

PMID- 10966061
TI  - Effect of interferon-gamma on experimental scleroderma induced by bleomycin.

PMID- 10966062
TI  - Melatonin protects human keratinocytes from UVB irradiation by light absorption.

PMID- 10966063
TI  - What can be done for my child?

PMID- 10966064
TI  - Neurologic, ophthalmic, and neuropsychiatric manifestations of pediatric systemic
      lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune, multisystem
      disorder with diverse manifestations. There are limited reports on the neuro
      ophthalmic and neuropsychiatric findings in childhood SLE. CASE REPORT: An 8-year
      old patient with suspected SLE with a history of skin rash, joint pain, transient
      hematologic abnormality, headaches, seizures, and psychosis, presented with
      papilledema secondary to acquired, obstructive hydrocephalus. DISCUSSION: SLE
      related ocular and neuropsychiatric findings are reviewed. Proposed mechanisms
      for ocular and cerebral lupus include immune complex deposition, vascular
      thrombosis, and postinflammatory lesions. CONCLUSION: The prevalent neurologic
      and neuropsychiatric complications of pediatric SLE require close follow-up and
      interdisciplinary management.

PMID- 10966065
TI  - A randomized trial of the effect of single-vision vs. bifocal lenses on myopia
      progression in children with esophoria.
AB  - BACKGROUND: Bifocals have long been thought to reduce progression of childhood
      myopia. However, this hypothesis has not been definitively evaluated. METHODS: We
      conducted a randomized clinical trial to test the hypothesis that bifocals slow
      myopia progression in children with near-point esophoria. Eighty-two myopic
      children were randomized to single-vision glasses (n = 40) or to bifocals with a
      +1.50 D add (n = 42) and were followed for 30 months. Refraction was measured by
      an automated refractor after cycloplegia. The primary outcome was myopia
      progression defined as the difference between the spherical equivalent at
      baseline and at the 30-month examination, averaged over both eyes. RESULTS:
      Follow-up was incomplete for six children in the bifocal group and one child in
      the single-vision group. Among the children completing the 30 months of follow
      up, myopia progression (mean spherical equivalent of the two eyes) averaged 0.99
      D for bifocals and 1.24 D for single vision (unadjusted, p = 0.106; adjusted for
      age, p = 0.046). Treatment groups differed in their cumulative distributions
      (Kolmogorov-Smirnov procedure, p = 0.031). Evidence for a treatment effect on
      growth in vitreous chamber depth was similar (p = 0.046 by K.S.). CONCLUSION: Use
      of bifocals, instead of single-vision glasses, by children with near-point
      esophoria seemed to slow myopia progression to a slight degree.

PMID- 10966066
TI  - The prevalence and symptoms of migraine in a consecutive series of patients
      attending an optometric practice.
AB  - The purpose of the investigation was to determine the prevalence of migraine in
      optometric practice and to document the variety of presentation. One thousand
      consecutively presenting patients of a suburban optometric practice were asked
      questions to establish whether they experience migraine or have experienced it in
      the past. Those with a history of migraine were asked further questions to
      establish the type of migraine and to document the variety of the symptoms they
      experienced. Eleven percent of male and 23% of female patients currently had
      migraine or had experienced it in the past. When corrected for the age
      distribution of the population of the state from which the sample was drawn, it
      is estimated that the general population prevalence of migraine is 9.5% for men
      and 19.7% for women. Half of the sample of migraineurs had not experienced a
      migraine within the last 12 months. A third had a known family history of
      migraine. Nearly half had not had a formal medical diagnosis of their migraine
      but only 7 had attended for optometric examination because of their migraine
      symptoms. Four of these patients had single migraine-like episodes and three had
      migraine equivalents (acephalic migraine, experiencing the visual aura without
      headache). Optometrists must be thoroughly familiar with migraine and its varied
      presentation because of its high prevalence, the explanatory value in offering a
      formal diagnosis of migraine, and the risk that headache or visual aura may be
      wrongly ascribed to migraine when there is some more sinister cause of the
      symptoms.

PMID- 10966067
TI  - Repeatability and intercorrelations of standard vision tests as a function of
      age.
AB  - PURPOSE: We assessed repeatability and intercorrelations of five standard vision
      tests in subjects with normal vision. METHODS: Seventy-eight subjects (aged 21 to
      68 years) completed five measurements each of high- and low-contrast visual
      acuity, near visual acuity and contrast sensitivity (Pelli-Robson chart).
      RESULTS: Except for correlations between high- and low-contrast visual acuity (r
      = 0.78), intercorrelations between tests were low to moderate (r < 0.5). For each
      measure, variability for the group was about one line on the chart (one triplet
      for the Pelli-Robson chart) and the minimum variability for an individual subject
      was about one third of this. On average, 1 to 2 lines can be expected to be lost
      over the normal lifespan on each test. Variability in responses did not increase
      significantly with age for any test. CONCLUSIONS: The criterion for judging
      change on commonly used clinical vision tests is about one line for subjects over
      a wide age range.

PMID- 10966068
TI  - Changes in stereoscopic depth perception caused by decentration of spectacle
      lenses.
AB  - The effect that decentered spectacle (ophthalmic) lenses exert on depth
      perception has been studied, evaluating stereopsis through the disparity range
      (maximum horizontal disparity) for random-dot stereograms (RDS). The results show
      that variations in fusional convergence due to increments of decentration can
      diminish the stereopsis in observers, reducing the region within which
      stereoscopic correspondence can take place. Decreases in disparity ranges were
      found for vertical and horizontal prismatic effects, although the prismatic
      effect necessary for this was less in the vertical case. A decreased disparity
      range has also been confirmed with figural-stimuli stereograms and using prisms
      for generating the prismatic effects.

PMID- 10966069
TI  - The presumed influence of attention on accuracy in the developmental eye movement
      (DEM) test.
AB  - BACKGROUND: The developmental eye movement (DEM) test is a clinical test used
      widely to evaluate ocular motility function (accuracy and speed) in school-age
      children. PURPOSE: The purpose of this study was to investigate, retrospectively,
      the change in accuracy over time while performing the DEM horizontal reading task
      in children. METHODS: The charts from children who had performed the DEM test
      during a routine eye examination in a pediatric optometry service were reviewed.
      The study included 22 patients (6 to 11 years old, 12 boys, 10 girls) who had a
      routine eye examination that was precepted by one of the authors (R.C.) during
      the period of 1995 to 1999. Patients were divided into two categories: 1) those
      with abnormal DEM test results and 2) a control group consisting of those with
      normal DEM test results. Chart review was done consecutively within each
      category. Collected data included patient age, gender, refractive error, and DEM
      test results. For analysis, the horizontal task of the DEM was divided into two
      halves (I and II), Part I always preceded part II, and data was sorted as the
      number of errors per part. RESULTS: More errors in accuracy occurred in part II
      than in part I (Wilcoxon signed rank test, p < or = 0.01) of the horizontal DEM
      test in the group of subjects with an abnormal DEM test. No differences in the
      number of errors in parts I and II of the horizontal task of the DEM were found
      in the control group. CONCLUSIONS: Findings showed that when excessive errors in
      accuracy occurred, the number of errors increased over time. If the errors were
      caused by an oculomotor dysfunction found in the DEM, errors should be equally
      distributed throughout the text. If errors were caused by fatigue, a difference
      in parts I and II should have occurred in both the test and the control group.
      These findings suggest that attention may influence accuracy over time in those
      patients that do poorly on the DEM test.

PMID- 10966070
TI  - Clinical quality assessment using computer monitor photoimages of optic nerve
      head cupping.
AB  - BACKGROUND: Photo documentation (color slides) of abnormal optic nerve heads
      enable the clinician to accurately access or estimate the percentage of the optic
      nerve cupping to quantify the progression of glaucoma. The purpose of this study
      is to compare cupping estimations using digital images on a computer monitor to
      those using standard color slides. METHODS: Ten sets of stereo optic nerve head
      photos from six glaucoma suspects were used in this study. A set is two 35-mm
      pictures of one optic nerve head. The film was developed as standard color slides
      using Seattle Filmworks slide developing. The computer monitor photoimages used
      Seattle Photoworks software for photos on disk. Thirteen experienced examiners
      estimated cupping on the 10 sets of color slides and on the 10 sets of digital
      images. Standard criterion was used to estimate the C/D percentage. We used a
      three-way mixed model ANOVA experimental design to analyze the data. RESULTS:
      Examiner estimations of C/D differed slightly between color slides and computer
      monitor photoimages (mean C/D of 61.1% for slides to 63.7% for monitor). This
      difference was statistically significant (p = 0.033). The differences authors
      found were not clinically significant (10%) in 7 out of the 10 optic nerve head
      photos using the accepted standard of interexaminer reliability. The variations
      of the examiner estimations as well as interexaminer differences will be
      discussed. CONCLUSION: The use of a computer image photodisplay of an optic nerve
      head has a potential as an alternative to traditional slide photodocumentation.
      This study identifies problems which require more work to make these computer
      images the equivalent of color slides.

PMID- 10966071
TI  - MK800-62F1, a new inhibitor of apoptotic cell death, from Streptomyces
      diastatochromogenes MK800-62F1. I. Taxonomy, fermentation, isolation, physico
      chemical properties and biological activity.
AB  - A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces
      diastatochromogenes MK800-62F1. It inhibited H2O2-induced apoptosis in human
      small cell lung carcinoma Ms-1 cells as well as in human T-cell leukemia Jurkat
      cells. In addition, MK800-62F1 also inhibited camptothecin-induced apoptosis in
      Jurkat cells, which was mediated by intracellular H2O2 generation. MK800-62F1 did
      not exhibit antioxidative activity in vitro, suggesting that inhibition of
      apoptosis by MK800-62F1 was not due to the scavenging of H2O2, rather it was due
      to the modulation of the downstream event of H2O2 generation.

PMID- 10966073
TI  - Luminacins: a family of capillary tube formation inhibitors from Streptomyces sp.
      I. Taxomony, fermentation, isolation, physico-chemical properties and structure
      elucidation.
AB  - A new family of capillary tube formation inhibitors, designated luminacins, has
      been discovered in the fermentation broth of a soil bacterium. The strain was
      identified as Streptomyces sp. Mer-VD1207 from taxonomic studies. By means of a
      series of chromatographic procedures, fourteen structurally related components,
      luminacins A1, A2, B1, B2, C1, C2, D, E1, E2, E3, F, G1, G2, and H, were
      isolated, and their structures were elucidated on the basis of spectroscopic
      analyses.

PMID- 10966072
TI  - MK800-62F1, a new inhibitor of apoptotic cell death, from Streptomyces
      diastatochromogenes MK800-62F1. II. Structure elucidation.
AB  - A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces
      diastatochromogenes MK800-62F1. The structure was determined by NMR analysis and
      degradation experiments.

PMID- 10966074
TI  - Luminacins: a family of capillary tube formation inhibitors from Streptomyces sp.
      II. Biological activities.
AB  - Twelve of the fourteen isolated components of the luminacin family were assayed
      for activity to inhibit capillary tube formation in vitro. Seven of them showed
      potent activity with IC50 values of less than 0.1 microg/ml in a rat aorta matrix
      culture model. Luminacin D, the strongest inhibitor, inhibited both endothelial
      cell proliferation and capillary tube formation. Morphological observation
      suggested that luminacin D inhibited the rearrangement of endothelial cells in
      the initial stage of tube formation. Luminacins and their derivatives are good
      candidates for application as angiogenesis inhibitors with a novel mechanism of
      action.

PMID- 10966075
TI  - Glomosporin, a novel antifungal cyclic depsipeptide from Glomospora sp. I.
      Production, isolation, physico-chemical properties and biological activities.
AB  - A novel antifungal cyclic depsipeptide termed glomosporin, which has a fatty acyl
      side chain, was isolated from a barley solid culture of Glomospora sp. The strain
      was isolated from fallen pine leaves collected in Fukusima Prefecture, Japan and
      identified as Glomospora sp. BAUA 2825. Glomosporin was purified by butanol
      extraction followed by preparative HPLC. Glomosporin showed antimicrobial
      activity against fungi including clinically important Aspergillus fumigatus.

PMID- 10966076
TI  - Argifin, a new chitinase inhibitor, produced by Gliocladium sp. FTD-0668. I.
      Taxonomy, fermentation, and biological activities.
AB  - A new chitinase inhibitor, named argifin, was isolated from the cultured broth of
      a fungal strain FTD-0668. The strain was identified as Gliocladium sp. from
      morphological characteristics. The IC50 value of argifin against Lucilia cuprina
      chitinase was 3.7 microM. Argifin arrested the moult of cockroach larvae upon
      injection into the ventral abdominal part.

PMID- 10966077
TI  - Argifin, a new chitinase inhibitor, produced by Gliocladium sp. FTD-0668. II.
      Isolation, physico-chemical properties, and structure elucidation.
AB  - A new chitinase inhibitor, named argifin, was isolated from the cultured broth of
      a fungal strain Gliocladium sp. FTD-0668. Argifin was purified from the cultured
      mycelium by the combination of cation exchange, anion exchange, adsorption, and
      gel filtration chromatographic methods. The structure of argifin was elucidated
      as cyclo(N(omega)-(N-methylcarbamoyl)-L-arginyl-N-methyl-L-phenylalan yl-beta-L
      aspartyl-beta-L-aspartyl-D-alanyl) by NMR experiments and other spectroscopic
      analyses.

PMID- 10966078
TI  - A new antimitotic substance, FR182877. III. Structure determination.
AB  - During the course of screening for novel cell cycle inhibitors, FR182877 was
      isolated from the fermentation broth of Streptomyces sp. No.9885. During the NMR
      measurements, FR182877 decomposed so much that the structure elucidation of
      FR182877 itself was difficult. Then, combinations of chemical correlations and
      spectroscopic methods clarified that FR182877 possesses an unprecedented multi
      ring system including the strained double bond, which was unexpectedly epoxidized
      by molecular oxygen. FR182877 showed broad antitumor activities in vitro and
      promoted assemblies of tublins in vitro as well as taxol. It is noteworthy that
      epoxidation of the distorted double bond resulted in significant decrease in
      antitumor activities.

PMID- 10966079
TI  - AB-400, a new tetraene macrolide isolated from Streptomyces costae.

PMID- 10966080
TI  - Dihydroniphimycin: new polyol macrolide antibiotic produced by Streptomyces
      hygroscopicus 15 isolation and structure elucidation.

PMID- 10966081
TI  - Immunosuppressant deoxyspergualin affects mitochondrial respiratory function in
      growing cells.

PMID- 10966082
TI  - Inhibition of rat embryo histidine decarboxylase by epoxyquinomicins.

PMID- 10966083
TI  - Structural characterization of the oligosaccharide antibiotics everninomicins by
      negative ion FAB and ESI/MS.

PMID- 10966084
TI  - Medical errors and patient safety: a growing research priority.

PMID- 10966085
TI  - Community health improvement approaches: accounting for the relative lack of
      impact.

PMID- 10966086
TI  - The Kaiser Family Foundation Community Health Promotion Grants Program: findings
      from an outcome evaluation.
AB  - OBJECTIVES: To present results from an outcome evaluation of the Henry J. Kaiser
      Family Foundation's Community Health Promotion Grants Program (CHPGP) in the
      West, which represented a major community-based initiative designed to promote
      improved health by changing community norms, environmental conditions, and
      individual behavior in 11 western communities. METHODS: The evaluation design: 14
      randomly assigned intervention and control communities, 4 intervention
      communities selected on special merit, and 4 matched controls. Data for the
      outcome evaluation were obtained from surveys, administered every two years at
      three points in time, of community leaders and representative adults and
      adolescents, and from specially designed surveys of grocery stores. Outcomes for
      each of the 11 intervention communities were compared with outcomes in control
      communities. RESULTS: With the exception of two intervention communities-a
      largely Hispanic community and a Native American reservation-we found little
      evidence of positive changes in the outcomes targeted by the 11 intervention
      communities. The programs that demonstrated positive outcomes targeted dietary
      behavior and adolescent substance abuse. CONCLUSIONS: Improvement of health
      through community-based interventions remains a critical public health challenge.
      The CHPGP, like other prominent community-based initiatives, generally failed to
      produce measurable changes in the targeted health outcomes. Efforts should focus
      on developing theories and methods that can improve the design and evaluation of
      community-based interventions.

PMID- 10966087
TI  - The effects of medical group practice and physician payment methods on costs of
      care.
AB  - OBJECTIVE: To assess the effects of payment methods on the costs of care in
      medical group practices. DATA SOURCES: Eighty-six clinics providing services for
      a Blue Cross managed care program during 1995. The clinics were analyzed to
      determine the relationship between payment methods and cost of care. Cost and
      patient data were obtained from Blue Cross records, and medical group practice
      clinic data were obtained by a survey of those organizations. STUDY DESIGN: The
      effects of clinic and physician payment methods on per member per year (PMPY)
      adjusted patient costs are evaluated using a two-stage regression model. Patient
      costs are adjusted for differences in payment schedules; patient age, gender, and
      ACG; clinic organizational variables are included as explanatory variables. DATA
      COLLECTION: Patient cost data were extracted from Blue Cross claims files, and
      patient and physician data from their enrollee and provider data banks. Medical
      group practice data were obtained by a mailed survey with telephone follow-up.
      PRINCIPAL FINDINGS: Capitation payment is correlated with lower patient care
      costs. When combined with fee-for-service with withhold provisions, this effect
      is smaller indicating that these two clinic payment methods are not
      interchangeable. Clinics with more physician compensation based on measures of
      resource use or based on some share of the net revenue of the clinic have lower
      patient care costs than those with more compensation related to productivity or
      based on salary. Salary compensation is strongly associated with higher costs.
      The use of physician profiles and clinical guidelines is associated with lower
      costs, but referral management systems have no such effect. The lower cost
      clinics are the smaller, multispecialty clinics. CONCLUSIONS: This study
      indicates that payment methods at both the medical group practice and physician
      levels influence the cost of care. However, the methods by which that influence
      is manifest is not clear. Although the organizational structure of clinics and
      their use of managed care programs appear to play a role, this influence is less
      than expected.

PMID- 10966088
TI  - The optimal outcomes of post-hospital care under medicare.
AB  - OBJECTIVE: To estimate the differences in functional outcomes attributable to
      discharge to one of four different venues for post-hospital care for each of five
      different types of illness associated with post-hospital care: stroke, chronic
      obstructive pulmonary disease (COPD), congestive heart failure (CHF), hip
      procedures, and hip fracture, and to estimate the costs and benefits associated
      with discharge to the type of care that was estimated to produce the greatest
      improvement. STUDY SETTING/DATA SOURCES: Consecutive patients with any of the
      target diagnoses were enrolled from 52 hospitals in three cities. Data sources
      included interviews with patients or their proxies, medical record reviews, and
      the Medicare Automated Data Retrieval System. ANALYSIS: A two-stage regression
      model looked first at the factors associated with discharge to each type of post
      hospital care and then at the outcomes associated with each location. An
      instrumental variables technique was used to adjust for selection bias. A
      predictive model was created for each patient to estimate how that person would
      have fared had she or he been discharged to each type of care. The optimal
      discharge location was determined as that which produced the greatest improvement
      in function after adjusting for patients' baseline characteristics. The costs of
      discharge to the optimal type of care was based on the differences in mean costs
      for each location. DATA COLLECTION/EXTRACTION METHODS: Data were collected from
      patients or their proxies at discharge from hospital and at three post-discharge
      follow-up times: six weeks, six months, and one year. In addition, the medical
      records for each participant were abstracted by trained abstractors, using a
      modification of the Medisgroups method, and Medicare data were summarized for the
      years before and after the hospitalization. PRINCIPAL FINDINGS: In general,
      patients discharged to nursing homes fared worst and those sent home with home
      health care or to rehabilitation did best. Because the cost of rehabilitation is
      high, greater use of home care could result in improved outcomes at modest or no
      additional cost. CONCLUSIONS: Better decisions about where to discharge patients
      could improve the course of many patients. It is possible to save money by making
      wiser discharge planning decisions. Nursing homes are generally associated with
      poorer outcomes and higher costs than the other post-hospital care modalities.

PMID- 10966089
TI  - The cost of work-related physical assaults in Minnesota.
AB  - OBJECTIVE: To describe the long-term productivity costs of occupational assaults.
      DATA SOURCES/STUDY SETTING: All incidents of physical assaults that resulted in
      indemnity payments, identified from the Minnesota Department of Labor and
      Industry (DLI) Workers' Compensation system in 1992. Medical expenditures were
      obtained from insurers, and data on lost wages, legal fees, and permanency
      ratings were collected from DLI records. Insurance administrative expenses were
      estimated. Lost fringe benefits and household production losses were imputed.
      STUDY DESIGN: The human capital approach was used to describe the long-term costs
      of occupational assaults. Economic software was used to apply a modified version
      of Rice, MacKenzie, and Associates' (1989) model for estimating the present value
      of past losses from 1992 through 1995 for all cases, and the future losses for
      cases open in 1996. PRINCIPAL FINDINGS: The total costs for 344 nonfatal work
      related assaults were estimated at $5,885,448 (1996 dollars). Calculation of
      injury incidence and average costs per case and per employee identified
      populations with an elevated risk of assault. An analysis by industry revealed an
      elevated risk for workers employed in justice and safety (incidence: 198/100,000;
      $19,251 per case; $38 per employee), social service (incidence: 127/100,000;
      $24,210 per case; $31 per employee), and health care (incidence: 76/100,000;
      $13,197 per case; $10 per employee). CONCLUSIONS: Identified subgroups warrant
      attention for risk factor identification and prevention efforts. Cost estimates
      can serve as the basis for business calculations on the potential value of risk
      management interventions.

PMID- 10966091
TI  - Continuous quality improvement and controlled trials are not mutually exclusive.

PMID- 10966090
TI  - Can continuous quality improvement be assessed using randomized trials? [see
      comment].
AB  - STUDY QUESTION: Continuous quality improvement (CQI) has been implemented at
      least to some degree in many health care settings, yet randomized controlled
      trials (RCTs) of CQI are rare. We ask whether, when, and how RCTs of CQI might be
      designed. STUDY DESIGN: We consider two applications of CQI: as a general
      philosophy of management and (by analogy with the use of conceptual models from
      the behavioral sciences) as a conceptual model for developing specific
      interventions. The example of warfarin therapy for stroke prevention among
      patients with atrial fibrillation is used throughout. PRINCIPAL FINDINGS: While
      it is impractical to use RCTs to study CQI as a general management philosophy,
      RCT methodology is appropriate for studying CQI as a conceptual model for
      generating interventions. RCTs of CQI might be considered when the process change
      under consideration is very large, its implications (e.g., in terms of cost,
      outcomes of care, etc.) are very great, and the best approach is uncertain. When
      designing RCTs of CQI, critical decisions include (1) the unit of randomization;
      (2) whether the focus is on CQI as a method for generating interventions or,
      instead, is on specific interventions in and of themselves; and (3) the
      flexibility available to local personnel to modify the intervention's operational
      details. CONCLUSIONS: RCTs of CQI as a conceptual model for generating
      interventions are feasible.

PMID- 10966092
TI  - Measuring the "managedness" and covered benefits of health plans.
AB  - STUDY AIMS: (1) To develop indexes measuring the degree of managedness and the
      covered benefits of health insurance plans, (2) to describe the variation in
      these indexes among plans in one health insurance market, (3) to assess the
      validity of the health plan indexes, and (4) to examine the association between
      patient characteristics and the health plan indexes. Measures of the
      "managedness" and covered benefits of health plans are requisite for studying the
      effects of managed care on clinical practice and health system performance, and
      they may improve people's understanding of our complex health care system. DATA
      SOURCES/STUDY SETTING: As part of our larger Physician Referral Study, we
      collected health insurance information for 189 insurance product lines and 755
      products in the Seattle, Washington metropolitan area, which we linked with the
      study's data for 2,277 patients recruited in local primary care offices. STUDY
      DESIGN: Managed care and benefit variables were constructed through content
      analysis of health plan information. Principal component analysis of the
      variables produced a managedness index, an in-network benefits index, and an out
      of-network benefits index. Bivariable analyses examined associations between
      patient characteristics and the three indexes. PRINCIPAL FINDINGS: From the
      managed care variables, we constructed three provider-oriented indexes for the
      financial, utilization management, and network domains of health plans. From
      these, we constructed a single managedness index, which correlated as expected
      with the individual measures, with the domain indexes, with plan type (FFS, PPO,
      POS, HMO), with independent assessments of local experts, and with patients'
      attitudes about their health insurance. For benefits, we constructed an in
      network benefits index and an out-of-network benefits index, which were
      correlated with the managedness index. The personal characteristics of study
      patients were associated with the managed care and benefit indexes. Study
      patients in more managed plans reported somewhat better health than patients in
      less managed plans. CONCLUSIONS: Indexes of the managedness and benefits of
      health plans can be constructed from publicly available information. The
      managedness and benefit indexes are associated with the personal characteristics
      and health status of study patients. Potential uses of the managed care and
      benefits indexes are discussed.

PMID- 10966093
TI  - Toward a redefinition of psychiatric emergency.
AB  - OBJECTIVE: To compare three methods for rating legitimate use of psychiatric
      emergency services (PES) in order to develop criteria that can differentiate
      appropriate from inappropriate PES service requests. METHOD: Ratings of PES
      visits by treating physicians and ratings of the same visits made during review
      of medical records. STUDY DESIGN: Two previously used methods of identifying
      justified PES service use were compared with the treating physician's rating of
      the same: (1) hospitalization as visit outcome and (2) retrospective chart
      ratings of visit characteristics using traditional medico-surgical criteria for
      "emergent" illness episodes. DATA EXTRACTION METHODS: Data were extracted through
      use of a physician questionnaire, and medical and administrative record review.
      PRINCIPAL FINDINGS: Agreement between the methods ranged from 47.1 percent to
      74.1 percent. A total of 21.7 percent of visits were rated as true health
      "emergencies" by the traditional definition, while 70.4 percent of visits were
      rated as "necessary" by treating physicians, and 21.0 percent resulted in
      hospitalization. Acuteness of behavioral dyscontrol and imminent dangerousness at
      the time of the visit were common characteristics of appropriate use by most
      combinations of the three methods of rating visits. CONCLUSIONS: The rating
      systems employed in similar recent studies produce widely varying percentages of
      visits so classified. However, it does appear likely that a minimum of 25-30
      percent of visits are nonemergent and could be triaged to other, less costly
      treatment providers. Proposed criteria by which to identify "legitimate"
      psychiatric emergency room treatment requests includes only patient presentations
      with (a) acute behavioral dyscontrol or (b) imminent dangerousness to self or
      others.

PMID- 10966094
TI  - Choice in a variable environment: every reinforcer counts.
AB  - Six pigeons were trained in sessions composed of seven components, each arranged
      with a different concurrent-schedule reinforcer ratio. These components occurred
      in an irregular order with equal frequency, separated by 10-s blackouts. No
      signals differentiated the different reinforcer ratios. Conditions lasted 50
      sessions, and data were collected from the last 35 sessions. In Part 1, the
      arranged overall reinforcer rate was 2.22 reinforcers per minute. Over
      conditions, number of reinforcers per component was varied from 4 to 12. In Part
      2, the overall reinforcer rate was six per minute, with both 4 and 12 reinforcers
      per component. Within components, log response-allocation ratios adjusted rapidly
      as more reinforcers were delivered in the component, and the slope of the choice
      relation (sensitivity) leveled off at moderately high levels after only about
      eight reinforcers. When the carryover from previous components was taken into
      account, the number of reinforcers in the components appeared to have no
      systematic effect on the speed at which behavior changed after a component
      started. Consequently, sensitivity values at each reinforcer delivery were
      superimposable. However, adjustment to changing reinforcer ratios was faster, and
      reached greater sensitivity values, when overall reinforcer rate was higher.
      Within a component, each successive reinforcer from the same alternative
      ("confirming") had a smaller effect than the one before, but single reinforcers
      from the other alternative ("disconfirming") always had a large effect. Choice in
      the prior component carried over into the next component, and its effects could
      be discerned even after five or six reinforcement and nonreinforcement is
      suggested.

PMID- 10966095
TI  - Shifts in the psychometric function and their implications for models of timing.
AB  - This study examined how two models of timing, scalar expectancy theory (SET) and
      learning to time (LeT), conceptualize the learning process in temporal tasks, and
      then reports two experiments to test these conceptualizations. Pigeons responded
      on a two-alternative free-operant psychophysical procedure in which responses on
      the left key were reinforceable during the first two, but not the last two,
      quarters of a 60-s trial, and responses on the right key were reinforceable
      during the last two, but not the first two, quarters of the trial. In Experiment
      1 three groups of birds experienced a difference in reinforcement rates between
      the two keys only at the end segments of the trial (i.e., between the first and
      fourth quarters), only around the middle segments of the trial (i.e., between the
      second and third quarters), or in both end and middle segments. In Condition 1
      the difference in reinforcement rate favored the left key; in Condition 2 it
      favored the right key. When the reinforcement rates differed in the end segments
      of the trial, the psychometric function--the proportion of right responses across
      the trial--did not shift across conditions; when it occurred around the middle of
      the trial or in both end and middle segments, the psychometric function shifted
      across conditions. Experiment 2 showed that the psychometric function shifts even
      when the overall reinforcement rate for the two keys is equal, provided the rates
      differ around the middle of the trial. This pattern of shifts of the psychometric
      function is inconsistent with SET. In contrast, LeT provided a good quantitative
      fit to the data.

PMID- 10966096
TI  - Drug discrimination under two concurrent fixed-interval fixed-interval schedules.
AB  - Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a
      two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food
      presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which
      the FI component with the shorter time requirement reinforced responding on one
      key after drug administration (pentobarbital-biased key) and on the other key
      after saline administration (saline-biased key). After responding stabilized
      under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66%
      (after pentobarbital) to 68% (after saline) of their reinforcers for responding
      under the FI 100-s component of the concurrent schedule. These birds made an
      average of 70% of their responses on both the pentobarbital-biased key after the
      training dose of pentobarbital and the saline-biased key after saline. After
      responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons
      earned an average of 67% of their reinforcers for responding under the FI 40
      component after both saline and the training dose of pentobarbital. These birds
      made an average of 75% of their responses on the pentobarbital-biased key after
      the training dose of pentobarbital, but only 55% of their responses on the saline
      biased key after saline. In test sessions preceded by doses of pentobarbital,
      chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response
      curves were similar under these two concurrent schedules. Pentobarbital,
      chlordiazepoxide, and ethanol produced dose-dependent increases in responding on
      the pentobarbital-biased key as the doses increased. For some birds, at the
      highest doses of these drugs, the dose-response curve turned over. Increasing
      doses of phencyclidine produced increased responding on the pentobarbital-biased
      key in some, but not all, birds. After methamphetamine, responding was largely
      confined to the saline-biased key. These data show that pigeons can perform drug
      discriminations under concurrent schedules in which the reinforcement frequency
      under the schedule components differs only by a factor of two, and that when
      other drugs are substituted for the training drugs they produce dose-response
      curves similar to the curves produced by these drugs under other concurrent
      interval schedules.

PMID- 10966097
TI  - Preference and resistance to change with constant-duration schedule components.
AB  - Previous research on preference between variable-interval terminal links in
      concurrent chains has most often used variable-duration terminal links ending
      with a single reinforcer. By contrast, most research on resistance to change in
      multiple schedules has used constant-duration components that include variable
      numbers of reinforcers in each presentation. Grace and Nevin (1997) examined both
      preference and resistance in variable-duration components; here, preference and
      resistance were examined in constant-duration components. Reinforcer rates were
      varied across eight conditions, and a generalized-matching-law analysis showed
      that initial-link preference strongly over-matched terminal-link reinforcer
      ratios. In multiple schedules, baseline response rates were unaffected by
      reinforcer rates, but resistance to intercomponent food, to extinction, and to
      intercomponent food plus extinction was greater in the richer component. The
      between-component difference in resistance to change exhibited additive effects
      for the three resistance tests, and was systematically related to reinforcer
      ratios. However, resistance was less sensitive to reinforcer ratios than was
      preference. Resistance to intercomponent food and to intercomponent food plus
      extinction was more sensitive to reinforcer ratios in the present study than in
      Grace and Nevin (1997). Thus, relative to variable-duration components, constant
      duration components increased the sensitivity of both preference and relative
      resistance, supporting the proposition that these are independent and convergent
      measures of the effects of a history of reinforcement.

PMID- 10966098
TI  - Equivalence classes in individuals with minimal verbal repertoires.
AB  - Studies from two different laboratories tested for equivalence classes in
      individuals with severe mental retardation and minimal verbal repertoires. In the
      first study, 3 individuals learned several matching-to-sample performances:
      matching picture comparison stimuli to dictated-word sample stimuli (AB),
      matching those same pictures to printed letter samples (CB), and also matching
      the pictures to nonrepresentative forms (DB). On subsequent tests, all
      individuals immediately displayed Emergent Relations AC, AD, BC, BD, CD, and DC,
      together constituting a positive demonstration of equivalence (as defined by
      Sidman). The second study obtained a positive equivalence test outcome in 1 of 2
      individuals with similarly minimal verbal repertoires. Taken together, these
      studies call into question previous assertions that equivalence classes are
      demonstrable only in individuals with well-developed language repertoires.

PMID- 10966099
TI  - Effects of competitive reward distribution on auditing and competitive
      responding.
AB  - This study allowed subjects to audit each other's responding during a series of
      competitive contests. Six pairs of female college students competed in 3-min
      contests in which the competitive response was a knob pull. A sum of money was
      divided using a proportional distribution or a 100%/0% reward distribution. In
      the proportional distribution, a subject's proportion of the sum was her
      proportion of the total number of responses. Also, in every contest either
      subject could make a response that would end the contest prematurely and give
      both subjects the same amount: a sum equal to 33% of the competitive total. Each
      subject could press either or both of two audit buttons that displayed her own
      and the other's response total for 10 s. Results replicated earlier findings in
      showing the superiority of the proportional distribution in total number of
      competitive responses made. No subject audited continuously, and only 1 audited
      most of the time. Most audits were interpersonal, including both own and other's
      scores. Auditing typically was more frequent in 100%/0% contests in which
      subjects were more likely to stop the contest when they were far behind. Winners
      were more likely to audit than were losers. Competitive response rates increased
      when the differences revealed by audits were small and decreased when they were
      large. Overall audit patterns were consistent with the view that feedback as
      "news" is more often sought when it can lead to improved outcomes.

PMID- 10966100
TI  - Equivalence relations and the reinforcement contingency.
AB  - Where do equivalence relations come from? One possible answer is that they arise
      directly from the reinforcement contingency. That is to say, a reinforcement
      contingency produces two types of outcome: (a) 2-, 3-, 4-, 5-, or n-term units of
      analysis that are known, respectively, as operant reinforcement, simple
      discrimination, conditional discrimination, second-order conditional
      discrimination, and so on; and (b) equivalence relations that consist of ordered
      pairs of all positive elements that participate in the contingency. This
      conception of the origin of equivalence relations leads to a number of new and
      verifiable ways of conceptualizing equivalence relations and, more generally, the
      stimulus control of operant behavior. The theory is also capable of experimental
      disproof.

PMID- 10966101
TI  - Motor function in the mitotic spindle.

PMID- 10966102
TI  - Flipping the switch: the structural basis for signaling through the CRIB motif.

PMID- 10966103
TI  - Cellular senescence: mitotic clock or culture shock?

PMID- 10966104
TI  - The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment
      and must be degraded to allow anaphase chromosome movement.
AB  - At anaphase, the linkage betweeh sister chromatids is dissolved and the separated
      sisters move toward opposite poles of the spindle. We developed a method to
      purify metaphase and anaphase chromosomes from frog egg extracts and identified
      proteins that leave chromosomes at anaphase using a new form of expression
      screening. This approach identified Xkid, a Xenopus homolog of human Kid (kinesin
      like DNA binding protein) as a protein that is degraded in anaphase by ubiquitin
      mediated proteolysis. Immunodepleting Xkid from egg extracts prevented normal
      chromosome alignment on the metaphase spindle. Adding a mild excess of wild-type
      or nondegradable Xkid to egg extracts prevented the separated chromosomes from
      moving toward the poles. We propose that Xkid provides the metaphase force that
      pushes chromosome arms toward the equator of the spindle and that its destruction
      is needed for anaphase chromosome movement.

PMID- 10966105
TI  - Xkid, a chromokinesin required for chromosome alignment on the metaphase plate.
AB  - Metaphase chromosome alignment is a key step of animal cell mitosis. The
      molecular mechanism leading to this equatorial positioning is still not fully
      understood. Forces exerted at kinetochores and on chromosome arms drive
      chromosome movements that culminate in their alignment on the metaphase plate. In
      this paper, we show that Xkid, a kinesin-like protein localized on chromosome
      arms, plays an essential role in metaphase chromosome alignment and in its
      maintenance. We propose that Xkid is responsible for the polar ejection forces
      acting on chromosome arms. Our results show that these forces are essential to
      ensure that kinetochores and chromosome arms align on a narrow equatorial plate
      during metaphase, a prerequisite for proper chromosome segregation.

PMID- 10966106
TI  - A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous
      system function and integrity.
AB  - Specific A-to-I RNA editing, like that seen in mammals, has been reported for
      several Drosophila ion channel genes. Drosophila possesses a candidate editing
      enzyme, dADAR. Here, we describe dADAR deletion mutants that lack ADAR activity
      in extracts. Correspondingly, all known Drosophila site-specific RNA editing (25
      sites in three ion channel transcripts) is abolished. Adults lacking dADAR are
      morphologically wild-type but exhibit extreme behavioral deficits including
      temperature-sensitive paralysis, locomotor uncoordination, and tremors which
      increase in severity with age. Neurodegeneration accompanies the increase in
      phenotypic severity. Surprisingly, dADAR mutants are not short-lived. Thus, A-to
      I editing of pre-mRNAs in Drosophila acts predominantly through nervous system
      targets to affect adult nervous system function, integrity, and behavior.

PMID- 10966107
TI  - Involvement of follicular stem cells in forming not only the follicle but also
      the epidermis.
AB  - The location of follicular and epidermal stem cells in mammalian skin is a
      crucial issue in cutaneous biology. We demonstrate that hair follicular stem
      cells, located in the bulge region, can give rise to several cell types of the
      hair follicle as well as upper follicular cells. Moreover, we devised a double
      label technique to show that upper follicular keratinocytes emigrate into the
      epidermis in normal newborn mouse skin, and in adult mouse skin in response to a
      penetrating wound. These findings indicate that the hair follicle represents a
      major repository of keratinocyte stem cells in mouse skin, and that follicular
      bulge stem cells are potentially bipotent as they can give rise to not only the
      hair follicle, but also the epidermis.

PMID- 10966108
TI  - Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.
AB  - It is well known that histone acetylases are important chromatin modifiers and
      that they play a central role in chromatin transcription. Here, we present
      evidence for novel roles of histone acetylases. The TIP60 histone acetylase
      purifies as a multimeric protein complex. Besides histone acetylase activity on
      chromatin, the TIP60 complex possesses ATPase, DNA helicase, and structural DNA
      binding activities. Ectopic expression of mutated TIP60 lacking histone acetylase
      activity results in cells with defective double-strand DNA break repair.
      Importantly, the resulting cells lose their apoptotic competence, suggesting a
      defect in the cells' ability to signal the existence of DNA damage to the
      apoptotic machinery. These results indicate that the histone acetylase TIP60
      containing complex plays a role in DNA repair and apoptosis.

PMID- 10966109
TI  - Nucleoid proteins stimulate stringently controlled bacterial promoters: a link
      between the cAMP-CRP and the (p)ppGpp regulons in Escherichia coli.
AB  - We report that the H-NS nucleoid protein plays a positive role in the expression
      of stringently regulated genes in Escherichia coli. Bacteria lacking both H-NS
      and the paralog StpA show reduced growth rate. Colonies displaying an increased
      growth rate were isolated, and mapping of a suppressor mutation revealed a base
      pair substitution in the spoT gene. The spoT(A404E) mutant showed low ppGpp
      synthesizing ability. The crp gene, which encodes the global regulator CRP, was
      subject to negative stringent regulation. The stable RNA/protein ratio in an hns,
      stpA strain was decreased, whereas it was restored in the suppressor strain. Our
      findings provide evidence of a direct link between the cAMP-CRP modulon and the
      stringent response.

PMID- 10966110
TI  - Translation/secretion coupling by type III secretion systems.
AB  - Type III secretion systems mediate export of virulence proteins and flagellar
      assembly subunits in Gram-negative bacteria. Chaperones specific to each class of
      secreted protein are believed to prevent degradation of the secreted substrates.
      We show that an additional role of chaperones may be to regulate translation of
      secreted proteins. We show that the chaperone FIgN is required for translation of
      the flgM gene transcribed from one mRNA transcript (a flagellar class 3
      transcript), but not from another (a flagellar class 2 transcript). FIgM
      translated from the class 3 transcript is primarily secreted whereas FIgM
      translated from the class 2 transcript is primarily retained in the cytoplasm.
      These results suggest FIgM and other type III secretion substrates possess both
      mRNA and amino acid secretion signals, and supports a new role for type III
      chaperones in translation/secretion coupling.

PMID- 10966111
TI  - The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling
      functions.
AB  - Ion channels have been studied extensively in ambient O2 tension (pO2), whereas
      tissue PO2 is much lower. The skeletal muscle calcium release channel/ryanodine
      receptor (RyR1) is one prominent example. Here we report that PO2 dynamically
      controls the redox state of 6-8 out of 50 thiols in each RyR1 subunit and thereby
      tunes the response to NO. At physiological pO2, nanomolar NO activates the
      channel by S-nitrosylating a single cysteine residue. Among sarcoplasmic
      reticulum proteins, S-nitrosylation is specific to RyR1 and its effect on the
      channel is calmodulin dependent. Neither activation nor S-nitrosylation of the
      channel occurs at ambient PO2. The demonstration that channel cysteine residues
      subserve coupled O2 sensor and NO regulatory functions and that these operate
      through the prototypic allosteric effector calmodulin may have general
      implications for the regulation of redox-related systems.

PMID- 10966112
TI  - Initiation of protein synthesis from the A site of the ribosome.
AB  - Positioning of the translation initiation complex on mRNAs requires interaction
      between the anticodon of initiator Met-tRNA, associated with eIF2-GTP and 40S
      ribosomal subunit, and the cognate start codon of the mRNA. We show that an
      internal ribosome entry site located in the genome of cricket paralysis virus can
      form 80S ribosomes without initiator Met-tRNA, eIF2, or GTP hydrolysis, with a
      CCU triplet in the ribosomal P site and a GCU triplet in the A site. P-site
      mutagenesis revealed that the P site was not decoded, and protein sequence
      analysis showed that translation initiates at the triplet in the A site.
      Translational initiation from the A site of the ribosome suggests that the
      repertoire of translated open reading frames in eukaryotic mRNAs may be greater
      than anticipated.

PMID- 10966113
TI  - Hedgehog induces opposite changes in turnover and subcellular localization of
      patched and smoothened.
AB  - Secreted signaling proteins of the Hedgehog family organize spatial pattern
      during animal development. Two integral membrane proteins have been identified
      with distinct roles in Hedgehog signaling. Patched functions in Hedgehog binding,
      and Smoothened functions in transducing the signal. Current models view Patched
      and Smoothened as a preformed receptor complex that is activated by Hedgehog
      binding. Here we present evidence that Patched destabilizes Smoothened in the
      absence of Hedgehog. Hedgehog binding causes removal of Patched from the cell
      surface. In contrast, Hedgehog causes phosphorylation, stabilization, and
      accumulation of Smoothened at the cell surface. Comparable effects can be
      produced by removing Patched from cells by RNA-mediated interference. These
      findings raise the possibility that Patched acts indirectly to regulate
      Smoothened activity.

PMID- 10966114
TI  - Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein
      ligases.
AB  - Ubiquitin-protein ligases (E3s) regulate diverse cellular processes by mediating
      protein ubiquitination. The c-Cbl proto-oncogene is a RING family E3 that
      recognizes activated receptor tyrosine kinases, promotes their ubiquitination by
      a ubiquitin-conjugating enzyme (E2) and terminates signaling. The crystal
      structure of c-Cbl bound to a cognate E2 and a kinase peptide shows how the RING
      domain recruits the E2. A comparison with a HECT family E3-E2 complex indicates
      that a common E2 motif is recognized by the two E3 families. The structure
      reveals a rigid coupling between the peptide binding and the E2 binding domains
      and a conserved surface channel leading from the peptide to the E2 active site,
      suggesting that RING E3s may function as scaffolds that position the substrate
      and the E2 optimally for ubiquitin transfer.

PMID- 10966115
TI  - Cytoplasmic dynein and microtubule transport in the axon: the action connection.
AB  - The neuron uses two families of microtubule-based motors for fast axonal
      transport, kinesin, and cytoplasmic dynein. Cytoplasmic dynein moves membranous
      organelles from the distal regions of the axon to the cell body. Because dynein
      is synthesized in the cell body, it must first be delivered to the axon tip. It
      has recently been shown that cytoplasmic dynein is moved from the cell body along
      the axon by two different mechanisms. A small amount is associated with fast
      anterograde transport, the membranous organelles moved by kinesin. Most of the
      dynein is transported in slow component b, the actin-based transport compartment.
      Dynactin, a protein complex that binds dynein, is also transported in slow
      component b. The dynein in slow component b binds to microtubules in an ATP
      dependent manner in vitro, suggesting that this dynein is enzymatically active.
      The finding that functionally active dynein, and dynactin, are associated with
      the actin-based transport compartment suggests a mechanism whereby dynein
      anchored to the actin cytoskeleton via dynactin provides the motive force for
      microtubule movement in the axon.

PMID- 10966116
TI  - Ionic and signal transduction alterations in Alzheimer's disease: relevance of
      studies on peripheral cells.
AB  - Several lines of evidence indicate that Alzheimer's disease (AD) has systemic
      expression. Systemic changes are manifested as alterations in a number of
      molecular and cellular processes. Although, these alterations appear to have
      little or no consequence in peripheral systems, their parallel expression in the
      central nervous system (CNS) could account for the principal clinical
      manifestations of the disease. Recent research seems to indicate that alterations
      in ion channels, calcium homeostasis, and protein kinase C (PKC) can be linked
      and thereby constitute a model of pathophysiological relevance. Considering the
      difficulties of studying dynamic pathophysiological processes in the disease
      ridden postmortem AD brain, peripheral tissues such as fibroblasts provide a
      suitable model to study molecular and cellular aspects of the disease.

PMID- 10966117
TI  - The early cellular pathology of Huntington's disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder that affects
      about one in 10,000 individuals in North America. The genetic defect responsible
      for the disease is an expansion of a CAG repeat that encodes a polyglutamine
      tract in the expressed protein, huntingtin. The disease is characterized by
      involuntary movements, cognitive impairment, and emotional disturbance. Despite
      the widespread expression of huntingtin, the brains of HD patients show selective
      neuronal loss in the striatum and the deep layers of the cerebral cortex. Recent
      studies have shown that polyglutamine expansion causes huntingtin to aggregate,
      to accumulate in the nucleus, and to interact abnormally with other proteins.
      Several cellular and animal models for HD have revealed that intranuclear
      accumulation of mutant huntingtin and the formation of neuropil aggregates
      precede neurological symptoms and neurodegeneration. Intranuclear huntingtin may
      affect nuclear function and the expression of genes important for neuronal
      function, whereas neuropil aggregates may interfere with neuritic transport and
      function. These early pathological events, which occur in the absence of
      neurodegeneration, may contribute to the neurological symptoms of HD and
      ultimately lead to neuronal cell death.

PMID- 10966121
TI  - On-line computer aided multi-component analysis using organic elemental analyzer
AB  - A computer program of on-line multi-component analysis for an organic elemental
      analyzer was described. Under the control of the proposed program, an elemental
      analyzer can perform both normal elemental analysis (EA) and multi-component
      analysis automatically. Eight mixtures of standard samples and nine synthetic
      copolymers were performed to check the reliability of program. The analytical
      results of styrene-N,N'-diisopropylacrylamide copolymer samples were compared
      with the determined results obtained from ultraviolet visible derivative
      spectroscopic (DS) method. The results show that the deviations for the mixtures
      of standard samples are < 2% for two and three components samples. In the case of
      synthetic copolymers, the average deviation between the two methods is 1.96%. It
      indicates that the proposed program is applicable for the combustion-GC type
      organic elemental analyzer.

PMID- 10966118
TI  - Ubiquitin-mediated proteolysis in learning and memory.
AB  - Sensitization of defensive reflexes in Aplysia is a simple behavioral paradigm
      for studying both short- and long-term memory. In the marine mollusk, as in other
      animals, memory has at least two phases: a short-term phase lasting minutes and a
      long-term phase lasting several days or longer. Short-term memory is produced by
      covalent modification of pre-existing proteins. In contrast, long-term memory
      needs gene induction, synthesis of new protein, and the growth of new synapses.
      The switch from short-term (STF) to long-term facilitation (LTF) in Aplysia
      sensory neurons requires not only positive regulation through gene induction, but
      also the specific removal of several inhibitory proteins. One important
      inhibitory protein is the regulatory (R) subunit of the cAMP-dependent protein
      kinase (PKA). Degradation of R subunits, which is essential for initiating long
      term stable memory, occurs through the ubiquitin-proteasome pathway.

PMID- 10966119
TI  - The unfolding story of two lissencephaly genes and brain development.
AB  - Formation of our highly structured human brain involves a cascade of events,
      including differentiation, fate determination, and migration of neural
      precursors. In humans, unlike many other organisms, the cerebral cortex is the
      largest component of the brain. As in other mammals, the human cerebral cortex is
      located on the surface of the telencephalon and generally consists of six layers
      that are formed in an orderly fashion. During neuronal development, newly born
      neurons, moving in a radial direction, must migrate through previously formed
      layers to reach their proper cortical position. This is one of several neuronal
      migration routes that takes place in the developing brain; other modes of
      migration are tangential. Abnormal neuronal migration may in turn result in
      abnormal development of the cortical layers and deleterious consequences, such as
      Lissencephaly. Lissencephaly, a severe brain malformation, can be caused by
      mutations in one of two known genes: LIS1 and doublecortin (DCX). Recent in vitro
      and in vivo studies, report on possible functions for these gene products.

PMID- 10966123
TI  - Reaction centre accessibility. II. Role of reaction centre congestion in the
      calculation of reaction centre accessibility
AB  - Accessibility to reaction centres is as important as electronic reactivity in
      determining the success of a reaction. The possibility of its calculation becomes
      a necessary requisite in the prediction of reaction products. Using a recently
      proposed approach to the calculation of reaction centre congestion based on a two
      dimensional representation of molecules, a new system has been realised that can
      quickly evaluate the desired accessibility. The system is based on the simulation
      of the steric interaction between reactants in different orientations. The
      calculation of an interaction energy for each orientation and their combination
      permits the approximate estimation of the reaction probability for the steric
      factors concerned. Even though all the operations were performed using a two
      dimensional representation the results are encouraging. It is obvious that at
      this level it is impossible to predict face accessibility preference.

PMID- 10966122
TI  - Reaction centre accessibility. I. Calculation of reaction centre congestion and
      influence of structure flexibility
AB  - The fate of a reaction depends on many factors like the electronic reactivity of
      the ground state molecules, conformation/configuration needs and solvent
      influence. It is often impossible to predict with any certainty the result, in
      terms of yield and products, of the interaction between two reactants. Thus the
      role of reaction centre accessibility is definitely determining but is itself
      difficult to determine. Nevertheless, within the framework of reaction product
      prediction it is essential to search for an acceptable solution of predictive
      modelling. A new approach to both the calculation of steric congestion near
      reaction centres and its regulation is presented as a first step towards the
      prediction of centre accessibility. The approach is based on a two dimensional
      representation of molecules and on the calculation of the steric congestion of
      each branch, calculated by means of intersecting circles that indicate the extent
      of the reactivity space and the congestion space.

PMID- 10966125
TI  - High-order spatial discretisations in electrochemical digital simulation. 1.
      Combination with the BDF algorithm
AB  - The application of fourth-order discretisations of the second derivative of
      concentration with respect to distance from the electrode, in electrochemical
      digital simulations, is examined. In the bulk of the diffusion space, a central
      five-point scheme is used, and six-point asymmetric schemes are used at the
      edges. In this paper, the scheme is applied to the BDF technique which allows
      higher orders in time as well. The method is found to be stable, using both the
      Neumann and matrix methods. Performance with BDF is not, however, optimal,
      levelling off at three-point BDF, as does the usual three-point approximation.
      This is shown to be due to startup problems inherent with BDF.

PMID- 10966124
TI  - Regularities in mutational variability in selected protein families and the
      Markovian model of amino acid replacement.
AB  - Three families of proteinase inhibitors and the trypsin family were the subjects
      of the analysis of amino acid replacements at aligned positions. This approach
      concerned some specific types of replacement and the mechanisms that can be
      involved in their control. The usefulness of the Markovian model for
      interpretation of mutational replacement within homologous proteins was examined.
      The same sequences were also analyzed with the use of the non-Markovian algorithm
      of genetic semihomology. This study leads to the conclusion that the Markovian
      model is not suitable for the interpretation of protein mutational variability
      since: (1) The information about the history of a variable unit is included in
      its genetic code. (2) This information plays an important role in the probability
      of further possible changes of the unit.

PMID- 10966126
TI  - Overlap integrals with g-orbitals
AB  - Formulae are derived for the overlap integrals between s-, p-, d-, f- or g
      orbitals at one centre and g-orbitals at the other one for any position of the
      two centres in the three dimensional space.

PMID- 10966127
TI  - Clustering of a molecular dynamics trajectory with a Hamming distance
AB  - Based on the properties of discrete point arrangements we introduce the concept
      of dynamical activity, which allows one to formulate a simple double criterion
      for locating clusters of homologous conformers in a molecular dynamics
      trajectory.

PMID- 10966120
TI  - Roles of transforming growth factor-alpha and related molecules in the nervous
      system.
AB  - The epidermal growth factor (EGF) family of polypeptides is regulators for tissue
      development and repair, and is characterized by the fact that their mature forms
      are proteolytically derived from their integral membrane precursors. This article
      reviews roles of the prominent members of the EGF family (EGF, transforming
      growth factor-alpha [TGF-alpha] and heparin-binding EGF [HB-EGF]) and the related
      neuregulin family in the nerve system. These polypeptides, produced by neurons
      and glial cells, play an important role in the development of the nervous system,
      stimulating proliferation, migration, and differentiation of neuronal, glial, and
      Schwann precursor cells. These peptides are also neurotrophic, enhancing survival
      and inhibiting apoptosis of post-mitotic neurons, probably acting directly
      through receptors on neurons, or indirectly via stimulating glial proliferation
      and glial synthesis of other molecules such as neurotrophic factors. TGF-alpha,
      EGF, and neuregulins are involved in mediating glial-neuronal and axonal-glial
      interactions, regulating nerve injury responses, and participating in injury
      associated astrocytic gliosis, brain tumors, and other disorders of the nerve
      system. Although the collective roles of the EGF family (as well as those of the
      neuregulins) are shown to be essential for the nervous system, redundancy may
      exist among members of the EGF family.

PMID- 10966128
TI  - ANN modeling of DNA sequences: new strategies using DNA shape code.
AB  - Two new encoding strategies, namely, wedge and twist codes, which are based on
      the DNA helical parameters, are introduced to represent DNA sequences in
      artificial neural network (ANN)-based modeling of biological systems. The
      performance of the new coding strategies has been evaluated by conducting three
      case studies involving mapping (modeling) and classification applications of
      ANNs. The proposed coding schemes have been compared rigorously and shown to
      outperform the existing coding strategies especially in situations wherein
      limited data are available for building the ANN models.

PMID- 10966129
TI  - Leukocyte counts and concentrations of soluble adhesion molecules as predictors
      of coronary atherosclerosis.
AB  - BACKGROUND: Authors of recent studies have reported that there is a relationship
      between level of adhesion molecules and atherosclerosis. In an animal study it
      was demonstrated that there is an interaction between adhesion molecules and
      leukocytes in atherosclerotic tissue. OBJECTIVE: To study the relationships
      between coronary-artery atherosclerosis and both differential blood-leukocyte
      count and concentrations of soluble adhesion molecules in patients with and
      without coronary artery disease (CAD). METHODS: Our subjects were 168 patients
      who underwent diagnostic coronary angiography. Forty-eight patients had normal
      coronary angiograms (control group), and 120 patients had significant coronary
      artery stenoses (diameter stenosis > 70%) in at least one major coronary-artery
      branch (CAD group). Total and differential blood-leukocyte counts, and
      concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and
      vascular cell adhesion molecule-1 (sVCAM-1) were assayed prior to angiography.
      RESULTS: Monocyte counts for patients in the CAD group were significantly greater
      than those for patients in the control group (366 +/- 99 versus 258 +/-
      44/microl, P < 0.0001), as were the sICAM-1 concentrations (272 +/- 52 versus 203
      +/- 24 ng/ml, P < 0.0001). The mean concentrations of sVCAM-1 in members of the
      two groups were the same (671 +/- 138 versus 668 +/- 97 ng/ml, P=0.4). There was
      a higher incidence of significant coronary-artery stenosis among patients with
      both a high monocyte count and a high concentration of sICAM-1 (> or = mean + SD)
      than there was among patients with a low monocyte count and a low concentration
      of sICAM-1 (> or = mean - SD; 100 versus 25%, P < 0.0001). CONCLUSIONS: Higher
      levels both of monocyte counts and of serum concentrations of ICAM-1 may serve as
      markers for coronary atherosclerosis.

PMID- 10966131
TI  - High level of cholesterol increases coronary vasomotor tone during exercise.
AB  - BACKGROUND: Coronary vasomotor tone plays an important role in the regulation of
      myocardial perfusion and influences ischemic threshold significantly. Endothelial
      dysfunction occurs in the presence of coronary risk factors and is closely linked
      to the development of atherosclerosis affecting myocardial perfusion and
      decreasing ischemic threshold. OBJECTIVE: To study the effect of
      hypercholesterolemia on coronary vasomotor tone in normal and stenotic coronary
      arteries at rest and during exercise. PATIENTS AND METHODS: In total 48 patients
      were included in the present analysis. Patients were divided into two groups
      according to the actual levels of serum cholesterol: 18 patients had normal (mean
      181 +/- 28 mg%; group 1) and 30 had elevated (mean 263 +/- 46 mg%; group 2)
      levels of serum cholesterol according to the 4S criteria with a cutoff level of
      213 mg% (5.5 mmol/l). Coronary vasomotor tone at rest and during supine bicycle
      exercise was calculated by dividing mean aortic pressure by radius of coronary
      vessel obtained using biplanar quantitative coronary angiography. A normal as
      well as a stenotic vessel segment in each patient were studied. RESULTS: Normal
      vessel segments in patients with normal levels of cholesterol (group 1) exhibited
      no exercise-induced change in coronary vascular tone (+3%, NS), whereas a
      significant increase in tone (+24%, P < 0.01 versus rest) occurred in those with
      high levels of cholesterol (group 2). In contrast, stenotic segments in members
      of both groups exhibited an increase in vascular tone irrespective of the actual
      level of serum cholesterol. CONCLUSIONS: Hypercholesterolemia causes a pathologic
      increase in coronary vasomotor tone of angiographically normal vessel segments
      during exercise. A similar pathologic response occurs in stenotic arteries, but
      this is independent of the actual level of serum cholesterol. These findings
      suggest that hypercholesterolemia influences vasomotor tone of the nonstenosed
      coronary arteries in patients with coronary artery disease probably through the
      occurrence of endothelial dysfunction.

PMID- 10966130
TI  - Repeat intervention for in-stent restenosis: re-expansion of the initial stent is
      a predictor of recurrence of restenosis.
AB  - BACKGROUND: In-stent restenosis has become a significant clinical problem as use
      of stents has increased. The optimal strategy for dealing with in-stent
      restenosis needs to be evaluated. OBJECTIVE: To compare the acute and late
      results of interventions for in-stent restenosis according to the device used,
      and to analyze the clinical and procedural variables of the lesions treated and
      identify the determinants of recurrence of restenosis and target lesion
      revascularization (TLR). METHODS: Procedural and late outcomes for 58 lesions in
      50 patients who underwent repeat intervention for in-stent restenosis were
      analyzed. The results of interventions according to the device employed were
      compared. The predictors of recurrence of restenosis and TLR within 6 months were
      analyzed. The ratio of balloon diameter in repeat intervention to minimal lumen
      diameter after initial stenting (MLD0) was used as an index of re-expansion of
      stents. Serial intravascular ultrasound imaging was performed before and after
      repeat intervention for 33 lesions, and re-expansion of the initial stent was
      evaluated. RESULTS: Repeat intervention was successful in treating all lesions.
      Angiographic follow-up was possible for 49 lesions (84%). The overall incidences
      of recurrence of restenosis and TLR were 40.1 and 27.6%, respectively. Despite
      the immediate results having been good, the late results of stenting for in-stent
      restenosis were not favorable. Diffuse-type in-stent restenosis, early in-stent
      restenosis, and balloon diameter:MLD0 ratio > 1.25 are independent predictors of
      poor late results. Intravascular ultrasound findings have shown that expansion of
      the initial stent leads to recurrence of restenosis and TLR. CONCLUSIONS: Re
      expansion of the initial stent can cause further vascular injury and there is a
      risk of recurrence of restenosis. Alternative therapeutic strategies that work
      without dilating the initial stent may be necessary for treating lesions with
      high risk of recurrence of restenosis.

PMID- 10966132
TI  - Bradycardia is associated with development of coronary collateral vessels in
      humans.
AB  - BACKGROUND: The development of mature coronary collateral vessels in patients
      with obstructive coronary artery disease (CAD) decreases the ischemic myocardial
      burden. Chronic bradycardia has been shown to stimulate formation of collateral
      vessels in experimental models. OBJECTIVE: To test our hypothesis that CAD
      patients with bradycardia would have better developed collateral circulation than
      would members of a control group. DESIGN: A retrospective study examining the
      relationship between bradycardia and the development of coronary collateral
      vessels in patients with obstructive CAD. METHODS: Admission electrocardiograms
      and rhythm tracings obtained during angiography of all patients presenting to the
      cardiac catheterization laboratory were screened from January to October 1997.
      Angiograms for patients with heart rates < or = 50 beats/min were reviewed. An
      equivalent number of consecutive patients with heart rates > or = 60 beats/min
      served as controls. Patients with acute myocardial infarction, with rhythms other
      than sinus, and without high grade obstructive CAD (< 70% stenosis) were excluded
      from the study. RESULTS: The study population consisted of 61 patients, 30 having
      heart rates < or = 50 beats/min (group A), and 31 controls with heart rates > or
      = 60 beats/min (group B). A significantly greater proportion of patients in group
      A than of matched controls was demonstrated to have developed collaterals (97
      versus 55% in group B, P < 0.005). The mean collateral grades were 1.66 and 0.95
      for subjects in groups A and B, respectively (P < 0.001). CAD patients with
      bradycardia are more likely (odds ratio 24, 95% confidence interval 5-146) to
      have angiographic coronary collaterals than are those with higher heart rates.
      CONCLUSION: Results of this study demonstrate that there is an association
      between bradycardia and growth of collateral vessels in patients with obstructive
      CAD. Bradycardic agents may be useful for promoting development of coronary
      collaterals in patients with atherosclerotic disease.

PMID- 10966133
TI  - The effects of uncontrolled hyperglycemia on thrombosis and formation of
      neointima after coronary stent placement in a novel diabetic porcine model of
      restenosis.
AB  - BACKGROUND: Results of recent clinical studies suggest that patients with
      diabetes mellitus have a higher than normal rate of restenosis after percutaneous
      transluminal coronary angioplasty or coronary stenting. The mechanism for this
      exaggerated neointimal response is not known. OBJECTIVES: To determine the
      technical feasibility of a model of in-stent restenosis in swine with
      streptozotocin-induced hyperglycemia and to compare the late arterial responses
      to injury induced by placement of oversized coronary stents in diabetic and
      nondiabetic animals. METHODS: Eighteen 25-40 kg castrated male or intact female
      Yucatan miniature swine aged 6 months were obtained from a commercial supplier.
      Twelve of the miniature swine were randomly selected for intravenous treatment
      with 125 mg/kg streptozotocin to induce a hyperglycemic state. Twelve weeks after
      treatment, all animals underwent placement of oversized balloon-expandable
      stainless steel stents in the coronary arteries. After 28 days, histomorphometric
      analysis of the stented coronary arteries to determine the neointimal responses
      for the diabetic and nondiabetic animals was completed. RESULTS: Sudden death due
      to stent thrombosis occurred for five of 11 (45%) of the diabetic animals and
      none of the age-matched nondiabetic control animals (P=0.05). For histology after
      28 days, the neointimal response was correlated to the extent of arterial injury
      for the diabetic (r=0.79, P < 0.0001) and nondiabetic (r=0.86, P < 0.0001)
      animals. The surviving diabetic animals had areas of neointimal (1.67 +/- 0.74
      mm2) and percentages of in-stent stenosis (28 +/- 14) similar to those of the
      nondiabetic swine (1.36 +/- 0.40 mm2, P=0.26; 22 +/- 6, P=0.17). Multiple
      regression analysis also demonstrated that arterial injury (P < 0.0001) alone,
      not hyperglycemia (P=0.237), was independently correlated to formation of
      neointima. CONCLUSIONS: Uncontrolled hyperglycemia results in greater than normal
      thrombosis after coronary-stent placement in swine with streptozotocin-induced
      diabetes. These data suggest that greater than normal early formation of thrombus
      rather than proliferation of smooth muscle cells contributes to restenosis after
      coronary stenting in patients with diabetes mellitus.

PMID- 10966135
TI  - Correlation between electrocardiographic subtypes of anterior myocardial
      infarction and regional abnormalities of wall motion.
AB  - BACKGROUND: Examination of the electrocardiogram is the most widely used means
      for diagnosis and early stratification of risk of acute myocardial infarction
      (AMI). The classical classification of the subtypes of anterior AMI is based on
      results of studies comparing the electrocardiograms recorded at various stages,
      mostly in the subacute or chronic stage of AMI, with autopsy findings. Reports
      regarding the correlation between electrocardiographic findings in the acute
      phase and regional abnormality of wall motion (AWM) detected by echocardiographic
      evaluation are sparse. OBJECTIVE: To investigate the relationship between the
      electrocardiographic and two-dimensional echocardiographic findings regarding
      patients with their first anterior AMI. DESIGN AND METHODS: We studied 58
      patients, 44 men and 14 women of mean age 61.5 +/- 14.6 years, with their first
      anterior AMI who had undergone two-dimensional echocardiographic evaluation
      within 48 h of admission. Deviation of ST-segment trace from baseline was
      measured manually 0.06 s after the J point for all leads on the admission
      electrocardiogram. ST-segment elevation in the various leads was correlated to
      the incidence of regional AWM detected by echocardiography. RESULTS: ST-segment
      elevations > or = 0.1 mV in V1 leads were found for 21 (36.2%) patients. Basal
      anterior, basal anteroseptal, and basal septal AWM were seen more often for
      patients with than they were for patients without ST-segment elevation in V1 (57
      versus 16%, P=0.003; 43 versus 13.5%, P=0.03; 43 versus 11%, P=0.01
      respectively). In contrast to ST-segment elevation in lead V1, the only
      statistically significant difference in prevalence in the presence of regional
      AWM between patients with (n = 48) and without (n = 10) ST-segment elevation > or
      = 0.2 mV in lead V2 was in the inferoapical region (87.5 versus 40%; P=0.003). ST
      segment elevation > or = 0.1 mV in leads aVL and V5 was found for 11 (19%) and 23
      (40%) patients, respectively. There was no correlation between either lateral or
      apical regional AWM and the presence of ST-segment elevation in the anterolateral
      leads except for mid-lateral AWM, which was more often detected for patients with
      than it was for patients without ST-segment elevation in aVL leads (36.3 versus
      6.4%, P=0.026). CONCLUSIONS: ST-segment elevation in lead V1 during the acute
      phase of anterior AMI is associated with a high incidence of regional AWM in the
      basal anterior, anteroseptal, and anterior regions, whereas ST-segment elevation
      in lead V2 is more often associated with AWM in the inferoapical region. ST
      segment elevation in aVL leads is related to mid-lateral regional AWM.

PMID- 10966134
TI  - Role of tissue factor-mediated coagulation in ischemia/ reperfusion-induced
      injury of Langendorf-perfused rabbit hearts.
AB  - BACKGROUND: Production of oxygen free radicals, and activation of neutrophils and
      plasma complement contribute to myocardial reperfusion injury, but the role of
      coagulation has not been assessed. OBJECTIVE: To characterize tissue-factor
      mediated generation of thrombin and its association with tissue injury during
      reperfusion from normothermic ischemia of isolated, Langendorf-perfused rabbit
      hearts. METHODS: Activation of coagulation was assessed by addition of 12% rabbit
      plasma and human fibrinogen to Krebs-Henseleit-buffer perfusate with measurement
      of levels of human fibrinopeptide A (hFPA) in the heart effluent as an index of
      thrombin-mediated formation of fibrin. RESULTS: Concentrations of hFPA in the
      effluent were minimal during non-ischemic perfusion (5 +/- 5 ng/ml, n=6) and
      during 50 min of ischemia (13 +/- 3 ng/ml, n=6), but increased markedly during
      the first 20 min of reperfusion (to 41 +/- 29 ng/ml, P=0.03 versus before
      reperfusion). Addition to the perfusate of 10 microg/ml recombinant human tissue
      factor-pathway inhibitor, the physiologic inhibitor of tissue-factor-mediated
      coagulation, abolished increases in the level of hFPA after reperfusion. However,
      indexes of myocardial injury manifested during reperfusion, including decrease in
      recovery of left ventricular pressure developed, increase in left ventricular end
      diastolic pressure, and increase in activity of creatine kinase in the heart
      effluent, were not improved by anticoagulation with recombinant human tissue
      factor-pathway inhibitor. CONCLUSION: Our results do not support the hypothesis
      that coagulation plays a major role in ischemia/reperfusion injury of Langendorf
      perfused rabbit hearts.

PMID- 10966136
TI  - In-vivo measurements of wall shear stress in human coronary arteries.
AB  - BACKGROUND: Wall shear stress (WSS) is closely associated with arteriosclerosis.
      WSS values for various vessels and species are available, but fully in-vivo
      measurements in human coronary arteries have not yet been reported. OBJECTIVE: To
      measure WSS in undiseased coronary arteries of adult patients at rest. METHODS:
      We recorded the temporal average value (APV) of the instantaneous maximal blood
      velocity in the three vessel segments of angiographically normal coronary artery
      bifurcations in 21 patients undergoing cardiac catheterization to treat various
      diseases by means of a 0.036 cm Doppler wire (FloWire). In total, 36 bifurcations
      were examined. The 36 x 3 cross-sectional areas (CSA) were determined by means of
      a three-dimensional angiographic technique. The three flows, Q1 (inflow), Q2, and
      Q3 of each bifurcation were calculated according to Q=0.5 x APV x CSA. For each
      segment, WSS was calculated as WSS=32 eta Q/(pi D3) (where blood viscosity
      eta=3.5 mPa s and D is vessel diameter). Only the 54 WSS values obtained from the
      18 flow triplets which satisfied the equation Q1/(Q2+Q3)=1 better than did the 18
      other ones were retained. RESULTS: The 54 WSS values ranged from 0.33 to 1.24 Pa
      (mean 0.68 Pa, SEM, 0.027 Pa). They did not depend significantly on Q (r=0.07;
      P=0.60) and the CSA (r=0.24, P=0.08) but the second relationship approached
      significance. CONCLUSION: The obtained mean WSS value (0.68 Pa) is half the value
      predicted for coronary arteries from optimality principles. It is also smaller
      than many values reported for human carotid, renal, and femoral arteries.

PMID- 10966137
TI  - Direct stenting without predilatation: a new approach to coronary intervention.
AB  - BACKGROUND: Implantation of coronary stents after predilatation is a standard
      approach in the treatment of most coronary lesions. Stenting without
      predilatation could be a possible alternative way of treating a certain subset of
      patients. OBJECTIVE: To identify a group of patients suitable for this optional
      method, to evaluate their immediate clinical and angiographic outcomes and to
      test the feasibility and safety of this new therapeutic concept. METHODS: Ninety
      selected patients with 91 lesions were treated by implantation of coronary stents
      without predilatation. RESULTS: The mean duration of this procedure was 12.3 +/-
      9.1 min and the fluoroscopic time was 3.6 +/- 2.9 min. The stenoses before and
      after this procedure were 77 +/- 10 and 5 +/- 9%, respectively. Predilatation,
      postdilatation or implantation of an additional stent was necessary for seven
      patients. Primary success rate was 92% with an excellent immediate clinical and
      angiographic outcome. No major complications occurred during direct stenting.
      CONCLUSION: Direct stenting is feasible using commercially available stents and
      could be performed for about 20% of patients for whom coronary intervention is
      indicated. The proper selection of lesions is of crucial importance. Lesions
      eligible for direct stenting should be without visible calcifications and on
      vessels without proximal tortuosity. This procedure proved to be safe and
      successful in this series of coronary interventions.

PMID- 10966138
TI  - Bibliography current world literature.

PMID- 10966139
TI  - The use of the rapid exchange grip test in detecting sincerity of effort, Part I:
      administration of the test.
AB  - A review of studies that utilize the rapid exchange grip (REG) test revealed that
      there is no standardized test protocol for administering the test. The purpose of
      this study was to investigate three factors that affect the result of the REG
      test: the hand switch rate, the number of grips performed during the test, and
      the comparative tests used in the interpretation of the REG test. The 146
      uninjured subjects performed a series of randomized grip strength tests including
      the REG test, the maximal static grip test (MSGT), and the five-rung (5R) test
      while making maximal and submaximal efforts. Results revealed no significant
      differences in peak REG scores between hand switch rates of 45 and 60 rpm.
      Significant differences were found for peak REG scores obtained from three vs.
      five trials. Peak scores from the 5R test vs. the MSGT differed significantly for
      maximal efforts but not for submaximal efforts. These results led to the
      following recommendations for a standardized protocol for administering the REG
      test: 1) the REG maneuver may be administered at a rate of either 45 or 60 rpm;
      2) at least five hand-grip exchanges must be performed; and 3) only one
      comparative test, either the MSGT or the 5R test, should be used consistently for
      comparison with the REG maneuver. The findings of the present study, however, did
      not verify which static grip test should be used for comparison with REG scores.

PMID- 10966140
TI  - The use of the rapid exchange grip test in detecting sincerity of effort, Part
      II: validity of the test.
AB  - The rapid exchange grip (REG) test was developed to identify patients exerting
      insincere effort. The premise of the REG test is that a maximal, sincere effort
      yields a "negative REG," in which peak static grip (SG) scores are greater than
      peak REG scores, and that a submaximal, insincere effort yields a "positive REG,"
      in which REG scores are greater than SG scores. There is disagreement in the
      literature concerning what constitutes a positive REG test, suggesting that the
      REG may not be a valid measure of sincerity of effort. The purpose of the present
      study was to investigate the validity of the REG test by examining its premise as
      well as its sensitivity and specificity values. The 146 uninjured subjects
      performed a series of randomized grip strength tests, exerting both maximal and
      submaximal efforts. The tests included the REG at hand switch rates of 45 rpm
      (REG-45) and 60 rpm (REG-60), the maximal static grip test (MSGT), and the five
      rung test (5R). Our findings supported the concept of a "negative REG" for both
      REG maneuvers and both comparative SG tests. The concept of a "positive REG,"
      however, was supported only when peak REG scores were compared with peak 5R
      scores. The authors found relatively low sensitivity and specificity values,
      suggesting that the REG test may not be sensitive or specific enough to
      effectively detect sincerity of effort. The authors discuss the likelihood that
      mistakes will be made when the REG test is used to diagnose sincerity of effort
      and the possible consequences of making such mistakes.

PMID- 10966141
TI  - Effects of fingernail length on finger and hand performance.
AB  - The purpose of this study was to investigate effects of fingernail length on
      active range of motion (AROM) of the fingers, speed of finger manipulation,
      number of words typed, and grip strength. Fifteen normal women (mean age, 30
      years) performed measurements under four conditions--with no attached fingernails
      and with fingernails extending 2, 1, and 0.5 cm beyond the tip of the finger.
      Analyses of variance showed that: 1) with fingernails of all extended lengths,
      grip strength measured on the first setting of the Jamar hand dynamometer
      decreased; 2) with fingernails 1 and 2 cm in length, AROM, grip strength on the
      second dynamometer setting, and finger manipulation decreased; and 3) with
      fingernails 2 cm in length, typing speed decreased (p < 0.05). Long fingernails
      limit flexion of the finger joints, particularly the metacarpophalangeal joints.
      Lack of finger flexion will limit excursion of long flexors and extensors in
      patients. It is recommended that patients cut their fingernails to a length of
      0.5 cm to achieve optimal functional outcomes.

PMID- 10966142
TI  - Prospective analysis of splinting the first carpometacarpal joint: an objective,
      subjective, and radiographic assessment.
AB  - Predisposing factors contributing to the development of first carpometacarpal
      (CMC) osteoarthritis include an inherent laxity or incongruency of this joint, a
      shallow trapezium saddle, and heavy stresses placed on the joint with pinching
      and grasping. Splinting is a common mode of conservative treatment for CMC
      osteoarthritis. This study assessed the objective and subjective responses of
      patients with CMC osteoarthritis who wore short and long opponens splints, as
      well as radiographic changes associated with wearing of the splints. The study
      evaluated 26 hands. Each patient was assigned at random to wear the long or the
      short splint first. Patients wore the splints for one week. They then documented
      function in their splints (on 22 activities of daily living) and rated splint
      satisfaction and pain levels on visual analog scales. One week after application
      of the first splint, the second splint was applied and worn for one week, and all
      measures were repeated. On the final visit, tip pinches were evaluated and x-rays
      were taken to assess subluxation. One-way repeated-measure analysis and paired
      comparison were used to analyze the pinch, pain, radiographic, and splint-rating
      measures. Descriptive statistics were used to assess activity-of-daily-living
      function and splint preference. Both splints appear to reduce subluxation at the
      first CMC joint in patients with grades 1 and 2 osteoarthritis. The majority of
      the patients picked the short splint when asked at the end of the study which
      splint they preferred. The splints do not appear to increase pinch strength or
      affect pain levels associated with the performance of pinch strength
      measurements. This study supports anecdotal evidence that patients with CMC
      osteoarthritis get pain relief with splinting.

PMID- 10966143
TI  - The biomechanics of a thumb carpometacarpal immobilization splint: design and
      fitting.
AB  - Splinting for the common osteoarthritis of the carpometacarpal (CMC) joint of the
      thumb is infrequently described in the literature, but the few splints that are
      described include one or both adjacent joints. This paper describes the design
      and biomechanics of a custom-molded thumb CMC immobilization splint that excludes
      the thumb metacarpophalangeal and wrist joints. The problem of the imbalance of
      extrinsic extensor/abductor forces against the intrinsic flexor/adductor forces
      is described. The accompanying weakening of the thumb CMC capsule allows dorsal
      shifting of the proximal end of the metacarpal, producing pain. The splint
      described in this paper 1) prevents motion of the first metacarpal in relation to
      the other metacarpals, 2) prevents tilting (flexion) of the first metacarpal
      during pinch, and 3) allows unrestricted thumb metacarpal and wrist joint motion.
      Attention to detail during construction is required for an accurate pattern,
      precise positioning of the CMC joint during molding, accurate molding around the
      first metacarpal, and well-distributed pressure. This design may also be used for
      protection following thumb CMC arthroplasty or thumb CMC sprain or strain and as
      a base for thumb metacarpophalangeal and/or interphalangeal mobilization
      splinting.

PMID- 10966145
TI  - An alternative to turnbuckle splinting for elbow flexion.

PMID- 10966144
TI  - Clinical splinting successes: the thumb "strap splint" for dynamic instability of
      the trapeziometacarpal joint.

PMID- 10966146
TI  - Clinical research: impossible or possible?

PMID- 10966147
TI  - The prepubertal years: a uniquely opportune stage of growth when the skeleton is
      most responsive to exercise?
AB  - The growing years may be the most opportune time in life for exercise to result
      in large increases in bone density, enough to reduce the risk of fracture late in
      life. However, it is not known if there is an 'optimal' time during growth when
      the skeleton is most responsive to exercise. Comparing the osteotrophic response
      to exercise between pre- and peripubertal children is complex because: (i) the
      development of the skeleton within each stage of puberty is characterised by
      differing temporal patterns of growth in bone size and mass; (ii) the hormonal
      regulation of the skeleton is unique to each stage of puberty; and (iii) it is
      difficult to equate the relative mechanical load placed on the prepubertal
      compared with the pubertal skeleton. There are sound biological bases for the
      hypotheses being proposed for both the pre- and peripubertal years being the time
      when the skeleton is most responsive to exercise; that is, exercise may enhance
      bone formation in a synergistic fashion in the presence of growth hormone
      (prepubertal years) or sex steroids (peripubertal years). The paucity of data and
      the complex methodology make it difficult to draw conclusions as to the most
      opportune time during growth when exercise may lead to the greatest osteotrophic
      response. The limited data available support the notion that the prepubertal
      years may be the most opportune time, due to increases in bone density and
      periosteal expansion of cortical bone.

PMID- 10966148
TI  - Detraining: loss of training-induced physiological and performance adaptations.
      Part I: short term insufficient training stimulus.
AB  - Detraining is the partial or complete loss of training-induced adaptations, in
      response to an insufficient training stimulus. Detraining characteristics may be
      different depending on the duration of training cessation or insufficient
      training. Short term detraining (less than 4 weeks of insufficient training
      stimulus) is analysed in part I of this review, whereas part II will deal with
      long term detraining (more than 4 weeks of insufficient training stimulus). Short
      term cardiorespiratory detraining is characterised in highly trained athletes by
      a rapid decline in maximal oxygen uptake (VO2max) and blood volume. Exercise
      heart rate increases insufficiently to counterbalance the decreased stroke
      volume, and maximal cardiac output is thus reduced. Ventilatory efficiency and
      endurance performance are also impaired. These changes are more moderate in
      recently trained individuals. From a metabolic viewpoint, short term inactivity
      implies an increased reliance on carbohydrate metabolism during exercise, as
      shown by a higher exercise respiratory exchange ratio, and lowered lipase
      activity, GLUT-4 content, glycogen level and lactate threshold. At the muscle
      level, capillary density and oxidative enzyme activities are reduced. Training
      induced changes in fibre cross-sectional area are reversed, but strength
      performance declines are limited. Hormonal changes include a reduced insulin
      sensitivity, a possible increase in testosterone and growth hormone levels in
      strength athletes, and a reversal of short term training-induced adaptations in
      fluid-electrolyte regulating hormones.

PMID- 10966149
TI  - A review of injury characteristics, aging factors and prevention programmes for
      the older golfer.
AB  - Participation in the sport of golf has risen considerably, particularly amongst
      senior players whose age is categorised as 50 years or more. However, golf
      presents both potential health benefits and risks for this older group of
      players. The health risks are compounded by the fact that the musculoskeletal and
      cardiovascular systems of senior players may not be as efficient at withstanding
      the strains and stress of this type of repetitive exercise. It was the purpose of
      this review paper to investigate the age-related health issues facing senior
      golfers and to discuss appropriate intervention strategies to help minimise these
      detrimental effects. The literature search identified only a minimal amount of
      epidemiological information pertaining specifically to the older golfer. A number
      of case reports were found which described a variety of musculoskeletal and
      cardiovascular incidents involving senior players. There was evidence from the
      literature that many of the age-related changes affecting older players' risk
      profiles were preventable or treatable through exercise. It was the conclusion of
      the authors of this review that conditioning programmes were highly recommended
      for all older players irrespective of their level of participation. Not only
      could the programmes prevent injury, they also had the potential to improve
      performance. Such programmes should incorporate flexibility, strength, endurance,
      speed and balance exercises specifically tailored to the demands of golf in order
      to be effective. Exercise equipment did not need to be elaborate and home-based
      programmes incorporating bodyweight, weighted clubs or elastic tubing resistance
      could be utilised. Future research needs to focus more specifically on injury
      incidence and mechanisms amongst groups of senior golfers whose participation
      rates vary. Randomised controlled trials are also recommended to investigate the
      efficacy of specific golf-related exercise regimens in this segment of the older
      population.

PMID- 10966150
TI  - Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of
      muscle growth and strength.
AB  - Beta-hydroxy beta-methylbutyrate (HMB), a metabolite of the essential amino acid
      leucine, is one of the latest dietary supplements promoted to enhance gains in
      strength and lean body mass associated with resistance training. Unlike anabolic
      hormones that induce muscle hypertrophy by increasing muscle protein synthesis,
      HMB is claimed to influence strength and lean body mass by acting as an
      anticatabolic agent, minimising protein breakdown and damage to cells that may
      occur with intense exercise. Research on HMB has recently tested this hypothesis,
      under the assumption that it may be the active compound associated with the
      anticatabolic effects of leucine and its metabolites. While much of the available
      literature is preliminary in nature and not without methodological concern, there
      is support for the claims made regarding HMB supplementation, at least in young,
      previously untrained individuals. A mechanism by which this may occur is unknown,
      but research undertaken to date suggests there may be a reduction in skeletal
      muscle damage, although this has not been assessed directly. The response of
      resistance trained and older individuals to HMB administration is less clear.
      While the results of research conducted to date appear encouraging, caution must
      be taken when interpreting outcomes as most manuscripts are presented in abstract
      form only, not having to withstand the rigors of peer review. Of the literature
      reviewed relating to HMB administration during resistance training, only 2 papers
      are full manuscripts appearing in peer reviewed journals. The remaining 8 papers
      are published as abstracts only, making it difficult to critically review the
      research. There is clearly a need for more tightly controlled, longer duration
      studies to verify if HMB enhances strength and muscular hypertrophy development
      associated with resistance training across a range of groups, including
      resistance trained individuals.

PMID- 10966151
TI  - Upper extremity injuries in the paediatric athlete.
AB  - Injuries to the upper extremity in paediatric and adolescent athletes are
      increasingly being seen with expanded participation and higher competitive levels
      of youth sports. Injury patterns are unique to the growing musculoskeletal system
      and specific to the demands of the involved sport. Shoulder injuries include
      sternoclavicular joint injury, clavicle fracture, acromioclavicular joint injury,
      osteolysis of the distal clavicle, little league shoulder, proximal humerus
      fracture, glenohumeral instability and rotator cuff injury. Elbow injuries
      include supracondylar fracture, lateral condyle fracture, radial head/neck
      fracture, medial epicondyle avulsion, elbow dislocation and little league elbow.
      Wrist and hand injuries include distal radius fracture, distal radial physeal
      injury, triangular fibrocartilage tear, scaphoid fracture, wrist ligamentous
      injury thumb metacarpalphalangeal ulnar collateral ligament injury, proximal and
      distal interphalangeal joint injuries and finger fractures. Recognition of injury
      patterns with early activity modification and the initiation of efficacious
      treatment can prevent deformity/disability and return the youth athlete to sport.

PMID- 10966152
TI  - Injuries to athletes with disabilities: identifying injury patterns.
AB  - Participation in sport activities for people with disabilities continues to gain
      in popularity. With participation in sports, there is an inherent risk of injury.
      A review of current sport epidemiological studies was used and we concluded that
      injury patterns for this population are similar to those for athletes without
      disabilities. Injury data from Paralympic competitions dating back to 1976
      indicate that most elite athletes with disabilities seek medical care for illness
      and musculo-skeletal injuries. However, there are very limited injury data
      regarding Winter Paralympic events or skiing injuries. For those athletes who
      participate in Summer Paralympic events, abrasions, strains, sprains and
      contusions are more common than fractures and dislocations. However, location of
      injuries appears to be disability and sport dependent. Lower extremity injuries
      are more common in ambulatory athletes (visually impaired, amputee, cerebral
      palsy) and upper extremity injuries are more frequent in athletes who use a
      wheelchair. While it appears that the majority of the injuries occurring in this
      population are minor in nature, inconsistencies in the definition of injury in
      the literature make this conclusion tenuous. When injuries are expressed as time
      lost in participation, 52% of injuries resulted in 7 days lost or less, 29% in 8
      to 21 days lost and 19% in greater than 22 days lost. The only prospective study
      addressing injury rates of athletes with disabilities in a manner consistent with
      other sport epidemiological studies found an injury rate of 9.3 injuries per 1000
      athlete-exposures (AE). This injury rate is less than American football (10.1 to
      15/1000 AE) and soccer (9.8/1000 AE), and greater than basketball (7.0/1000 AE).
      It is unclear whether comparative statistics such as these take into
      consideration the number of illness and injury episodes that resulted from the
      disability. Further complicating epidemiological studies for athletes with
      disabilities is the definition of the population and samples of convenience which
      are frequently used. These samples are often not representative of the
      multiplicity of disability conditions, levels of competition and range of sport
      activities available. Prospective studies comparing athletes to sedentary control
      individuals to measure differences in injury rates, type and frequency between
      and within disability groups, sports and levels of competition are desperately
      needed to further the knowledge of injury trends and develop and establish
      accurate injury prevention programmes.

PMID- 10966153
TI  - Structure-property relationships on histamine H3-antagonists: binding of phenyl
      substituted alkylthioimidazole derivatives to rat plasma proteins.
AB  - The binding of a series of H3-antagonists to rat plasma proteins was investigated
      by dialysis experiments, with RP-HPLC measurement of the free ligand. The series
      was composed of 4(5)-phenyl-2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazoles having,
      on the phenyl ring, meta- and para-substituents, with different physico-chemical
      characteristics. As high protein binding had been proposed as being one of the
      features limiting brain access for the reference H3-antagonist thioperamide, the
      title series was employed to test the possibility of achieving lower protein
      binding by modulation of lipophilicity, while maintaining good receptor affinity.
      The compounds tested showed quotas of bound drug ranging from 60 to 97.5%, while
      for thioperamide a 78% bound drug quota was observed at high total
      concentrations, with a steep increase in bound percentage at lower
      concentrations. Two of the tested compounds, having a carboxamide substituent,
      showed lower protein binding compared to thioperamide over a wide range of total
      concentration, without a significant loss in affinity with respect to the parent
      compound. A strict dependence of protein binding on lipophilicity was observed,
      and a QSPR model was derived which could also account for the protein binding
      observed for thioperamide, while receptor affinity had been reported to be quite
      insensitive to phenyl ring substitution. It is therefore possible to modulate
      protein binding of these H3-antagonists, through lipophilicity adjustment,
      without losing receptor affinity; this finding could help in the design of new
      compounds with improved brain access.

PMID- 10966154
TI  - Anti-cancer activity studies of indolalthiohydantoin (PIT) on certain cancer cell
      lines.
AB  - 5-(2-Phenyl-3'-indolal)-2-thiohydantoin (PIT) has been evaluated as an anti
      cancer compound on several cancer lines organised in to subpanels representing
      leukemia, melanoma, and cancer of lung, colon, kidney, ovary, breast, prostate
      and central nervous system by the National Cancer Institute (NCI) anti-cancer
      drug screen programme. The compound showed inhibitory activity on several cancer
      cell lines. No information is available on anti-cancer potency of this compound
      with normal cell lines.

PMID- 10966155
TI  - Synthesis and evaluation of some new fluorinated hydroquinazoline derivatives as
      antifungal agents.
AB  - The key intermediate octahydroquinazoline (1) was obtained in one pot synthesis
      by a modification of the Biginelli reaction. Compound 1 was allowed to react with
      phenacyl bromide and bromomalononitrile to furnish thiazolo[2,3-b]quinazoline 3
      and 12, respectively. Interaction of compound 12 with formamide, formic acid and
      phenyl isothiocyanate yielded the corresponding pyrimidino[4',5':4.5]thiazolo[2,3
      b] quinazolines 13, 14 and 17, respectively. The structure of the synthesized
      compounds were elucidated by elemental analyses and spectroscopic analyses. Some
      of the prepared compounds were tested for their antifungal activity in comparison
      with tioconazole as a reference fungicide.

PMID- 10966156
TI  - Studies on arylfuran derivatives: part X. Synthesis and antibacterial properties
      of arylfuryl-delta2-pyrazolines.
AB  - Arylfurylpropenones 3 were synthesized by Claisen-Schmidt condensation of
      arylfurfurals 1 with various substituted acetophenones 2. Cyclocondensation of
      these arylfurylpropenones 3 with hydrazine hydrate and phenylhydrazine furnished
      1H-pyrazolines 4 and N-phenylpyrazolines 6, respectively. In order to study the
      structure-activity relationships, pyrazolines 4 were converted into their N
      acetyl derivatives 5. The antibacterial properties of the new pyrazoline
      derivatives were studied.

PMID- 10966157
TI  - Therapeutic proteins: a comparison of chemical and biological properties of
      uricase conjugated to linear or branched poly(ethylene glycol) and poly(N
      acryloylmorpholine).
AB  - Uricase from Bacillus fastidiosus (UC) was covalently linked to linear PEG (PEG
      1) (Mw 5 kDa), branched PEG (PEG-2) (Mw 10 kDa) and to poly(N-acryloylmorpholine)
      (PAcM) (Mw 6 kDa). The conjugation of UC with linear PEG and PAcM was accompanied
      by complete loss of enzymatic activity but, if uric acid as site protecting agent
      was included in the reaction mixture, the conjugate protein retained enzymatic
      activity. On the other hand, the modification with PEG-2 gave a conjugate that
      also maintained enzymatic activity in the absence of any active site protection.
      This behaviour must be related to hindrance of the branched polymer in reaching
      the enzyme active site. The UC conjugates exhibited increased resistance to
      proteolytic digestion while minor variations in the inhibitory constant, optimal
      pH, heat stability, affinity for substrate, were observed. Pharmacokinetic
      investigations in mice demonstrated increased residence time in blood for all the
      conjugates as compared with native uricase. Uricase conjugated with linear PEG
      was longer lasting in blood UC derivative, followed by branched PEG and the PAcM
      conjugates. Unconjugated uricase was rapidly removed from circulation. All these
      data are in favour of the use of the less known amphiphilic polymer PAcM as an
      alternative to PEGs in modification of enzymes devised for therapeutic
      applications.

PMID- 10966158
TI  - Pharmacokinetic monitoring of mycophenolate mofetil in kidney transplanted
      patients.
AB  - Mycophenolate mofetil (MMF) is a new immunosuppressant drug used in association
      with cyclosporin and oral corticosteroids to prevent acute rejection following
      renal allograft transplantation. MMF is an ester pro-drug of mycophenolic acid
      (MFA), the true active species, into which it is completely transformed after
      oral administration. The recommended initial dose to prevent kidney transplant
      rejection is 2 g/day irrespective of body weight, 1 g twice daily. The goal of
      this study was to correlate dosage (fixed or by body weight) and toxic effects to
      some non-compartmental values such as peak level (Cmax), time to peak level
      (Tmax) and trough level (Cmin). In a small number of patients who had already
      reached the plasma steady state, we found a large inter-patient variability,
      while the same qualitative pharmacokinetic profile (as Tmax) was conserved. At
      plasma trough level > 4 microg/ml some serious toxic effects were observed,
      whereas at Cmin < 2 microg/ml, there were some cases of interstitial rejection.
      There was also a negative correlation between dosage and body weight, suggesting
      that dosages related to body weight might be better than fixed ones. Finally,
      monitoring plasma level of drug from transplantation to at least 12 months after
      surgery, at fixed MFA dosage, a small but significant decline of MFA plasma
      levels was found.

PMID- 10966159
TI  - Interactions between DNA and benzo- and tetrahydrobenzofurocoumarins:
      thermodynamic and molecular modeling studies.
AB  - The non-covalent interaction of a series of new water-soluble benzo- and
      tetrahydrobenzofurocoumarins with salmon testes DNA has been studied using flow
      linear dichroism, circular dichroism, contact fluorescence energy transfer and
      ethidium bromide displacement assay. The new derivatives are characterised by
      having an alkyl amino side chain protonated at physiological pH; this fact
      strongly enhances the solubility in aqueous media and the affinity for the
      macromolecule. The results show significant difference in the affinity and the
      mode of binding among the examined compounds depending on the nature of the
      fourth condensed ring and the position of the alkylamino side chain.
      Benzofurocoumarins derivatives bind DNA by undergoing intercalation inside the
      duplex macromolecule, whereas tetrahydrobenzofurocoumarins derivatives show a
      substantial tilt relative to the base planes. Molecular modeling studies have
      been performed to characterise in detail the intercalation mechanism of these
      benzofurocoumarins to DNA.

PMID- 10966161
TI  - C-terminal anthranoyl-anthranilic acid derivatives and their evaluation on CCK
      receptors.
AB  - A series of C-terminal anthranoyl-anthranilic acid derivatives arising from a
      strict bond disconnection approach of asperlicin were synthesized and examined
      for their CCK receptor affinities. These compounds represent the second step of
      our investigation directed toward the search for alternative substructures of
      asperlicin as a starting point for the development of a new class of CCK ligands.
      The obtained micromolar affinities for CCK-A rather than CCK-B receptor confirm
      that the anthranilic acid dimer represents a useful template for the development
      of selective CCK-A receptor ligands.

PMID- 10966160
TI  - Synthesis and antifungal activity of novel pyrano[2',3':4,5]thiazolo[2,3
      b]quinazolines, pyrido[2',3':4,5]thiazolo[2,3-b]quinazolines and
      pyrazolo[2',3':4,5]thiazolo[2,3-b]quinazolines.
AB  - The starting materials thiazolo[2,3-b]quinazolines (5a,b) were obtained in one
      pot synthesis by treating octahydroquinazoline (2) with chloroacetic acid and
      aromatic aldehydes. Thiazoloquinazoline (5) was reacted with CH2(CN)2/piperidine
      and CH2(CN)2/NaOH (CH3OH), to furnish pyrano[2',3':4,5]thiazolo[2,3
      b]quinazolines (6a,b) and pyrido[2',3':4,5]thiazolo[2,3-b]quinazoline (7),
      respectively. Refluxing of 5a with NH2CSNH2/KOH and hydrazines in ethanol
      furnished the corresponding, [1,3]thiazino[4'5':4,5]thiazolo[2,3-b]quinazoline
      (10) and pyrazolo[3',4':4,5]thiazolo[2,3-b]quinazolines (11a,b), respectively.
      Antifungal activity was shown for some of the synthesized compounds.

PMID- 10966162
TI  - Clarithromycin targeting to lung: characterization, size distribution and in vivo
      evaluation of the human serum albumin microspheres.
AB  - Microspheres of clarithromycin have been prepared from human serum albumin using
      the emulsion polymerization technique. Albumin microspheres containing the active
      substance were injected into the tail vein of mice. Mice were sacrificed at
      intervals and microspheres collected from lungs and livers. The clarithromycin
      amount in microspheres was determined by reversed phase high performance liquid
      chromatographic (HPLC) method from the mice organs. Morphological and
      histopathological observations were also reported. The microsphere accumulation
      began at 10 min, and increased gradually until 6 h, then a decrease was observed.
      The microspheres were still present after 24 h. In the liver sample, no
      microsphere accumulation was observed at any time.

PMID- 10966163
TI  - Biscarbamate analogues of the chemotactic tripeptide fMLF-OMe.
AB  - Based on the sequence of the prototypical chemotactic tripeptide HCO-Met-Leu-Phe
      OH (fMLF) and by taking into account the versatility shown by its N-terminal
      carbamate analogues, the new biscarbamates MeOCO-Met-Leu-gPhe-COOMe (2) and Boc
      Met-Leu-gPhe-COOMe (4) were synthesized. These two new ligands are characterized
      by the presence of a gem-diamino residue (gPhe) replacing the C-terminal Phe and
      a carbamate functionality positioned at both the ends of the molecule. The
      activity of the two new compounds has been determined on human neutrophils and
      compared to that shown by the corresponding N-terminal monocarbamates MeOCO-Met
      Leu-Phe-OMe (1) and Boc-Met-Leu-Phe-OMe (3).

PMID- 10966164
TI  - Adsorption of omeprazole on latex particles and characterization of the complex.
AB  - Omeprazole is an antisecretory drug used against gastric ulcers. It quickly
      decomposes in an acid medium, however, therefore making it a matter of great
      interest to protect it in these conditions and determine the ideal adsorption
      conditions for this drug on latex particles for formulation designs--oral
      suspensions--containing polymers with the aim of delivering different drugs in a
      sustained and controlled action. Time, pH, and concentration of the active
      ingredient for which maximum adsorption occurs, were determined. The findings
      suggest that adsorption is evidently greatest at an acid pH 4-5, that the
      adsorption of Omeprazole rises concomitantly with the increase in latex
      particles, and the time is the least influential factor.

PMID- 10966165
TI  - Analgesic activity of cyclic imides: 1,8-naphthalimide and 1,4,5,8
      naphthalenediimide derivatives.
AB  - In early studies, we have reported the synthesis and biological activities of
      several cyclic imides. The present study describes the analgesic activity of 1,8
      naphthalimide and 1,4,5,8-naphthalenediimide derivatives in a standard murine
      model of analgesia. The pharmacological results show that all compounds studied,
      given intraperitoneally, produced significant inhibition of acetic acid-induced
      abdominal constrictions. At the ID50 (micromol/kg) level, these cyclic imide
      derivatives were about 40-270-fold more potent in this assay than aspirin and
      acetaminophen, two well-known and widely used analgesics. These results extend
      previous studies on the analgesic activity of cyclic imides.

PMID- 10966166
TI  - Synthesis and antiviral properties of novel analogues of monophosphate and
      diphosphate bioactive forms of acyclovir.
AB  - New analogues (compounds 6, 7 and 9) of the mono- (8) and diphosphate (10)
      bioactive forms of the antiherpes drug acyclovir are described. In compound 6,
      the monophosphate moiety of 8 was replaced by an aminosulfonyloxy group, while in
      compounds 7 and 9, a phosphonoacetamidoxy and an O-ethyl phosphonoacetamidoxy
      moiety are, respectively present instead of the diphosphate one of 10. None of
      the compounds synthesized proved to possess an appreciable activity on herpes
      simplex virus (HSV) or human immunodeficiency virus (HIV).

PMID- 10966167
TI  - Fetal hemoglobin expression in the compound heterozygous state for -117 (G-->A)
      Agamma HPFH and IVS-1 nt 110 (G-->A) beta+ thalassemia: a case study.
AB  - The splicing defect at IVS-I-110 is by far (43.15%) the most common beta
      thalassaemia mutation in Greece. The - 117 (G-->A) Agamma hereditary persistence
      of fetal hemoglobin (Greek HPFH) is also the most frequent nondeletional HPFH in
      Greece. We report a case in which these two defects co-segregates. She is a
      healthy female where the total Hb is 12.3 g/dl with 51% HbF and normal HbA2. Her
      Ggamma/Agamma ratio is 35:65 differing from that of 10 simple heterozygotes for
      the Greek HPFH who have ratio of 8:92. Molecular analysis of the beta-globin
      genotype revealed the presence of the IVS-I-110 beta+ mutation in trans to the 
      117 G-->A Greek HPFH. Both mutations are linked to Ia. Her father has Greek HPFH
      in trans to the -158 C-->T on the Ggamma promoter, which is linked with haplotype
      IIIalpha. He has 13% HbF with a Ggamma/Agamma ratio 32:68. Her sister is a
      compound heterozygote for the IVS-I-110 mutation in trans to the - 158 C-->T,
      with HbF levels of 3% and a Ggamma/Agamma ratio 72:28.

PMID- 10966168
TI  - EORTC QLQ-C30 and FACT-BMT for the measurement of quality of life in bone marrow
      transplant recipients: a comparison.
AB  - The purpose of the study was to compare two different quality-of-life self-rating
      instruments, namely the EORTC QLQ-C30, developed by the quality-of-life study
      group of the European Organisation for Research and Treatment of Cancer, and the
      FACT-BMT (version 3), the Functional Assessment of Cancer Therapy - Bone Marrow
      Transplantation scale, which is the FACT-G(eneral measure) in combination with a
      module developed specifically for evaluating quality of life of bone marrow
      transplant (BMT) patients. Fifty-six BMT recipients completed both the EORTC QLQ
      C30 and the FACT-BMT (German language version) during the same session.
      Questionnaire data were analyzed on a subscale basis using correlation analysis
      and multiple linear regression. Correlations between corresponding subscales of
      EORTC QLQ-C30 and the FACT-BMT ranged from r=0.30 for the emotional domain (poor
      agreement) to r=0.77 for global QOL (good agreement). This suggests that the
      instruments, despite considerable overlap, possibly focus on different aspects of
      QOL, in particular in addressing emotional and social issues of BMT patients. It
      appears that the FACT-BMT gives a more comprehensive overview regarding the
      multidimensional construct of quality of life. The EORTC QLQ-C30 gives more
      insight into the physical aspects of quality of life and helps to identify
      symptoms which effectively decrease quality of life from the patient's
      perspective. The QLQ-C30 might be improved by the incorporation of a BMT-specific
      module currently under development. We therefore conclude that neither of the two
      instruments can be replaced by the other in the assessment of QOL of BMT patients
      and that a direct comparison of results obtained with the two instruments is
      likely to be misleading.

PMID- 10966169
TI  - Assessment of peripheral blood lymphocyte subsets in idiopathic myelofibrosis.
AB  - The objective of this study was to contribute to a better characterization of the
      immunological profile of idiopathic myelofibrosis (IM) at presentation by
      analysing the blood lymphocyte subsets and their possible correlations with other
      disease features. Absolute blood lymphocytes and lymphocyte subsets were assessed
      in 31 IM patients, compared with those from 34 healthy individuals, and
      correlated with the patients' main clinical, hematological and bone marrow
      histologic features. The mean lymphocyte count of the IM patients was 1.1 (SD
      0.6) x 10(9)/L, versus 1.6 (SD 0.49) x 10(9)/L in controls (p = 0.0006), with 24
      of the 31 patients (77.4%) showing lymphocytopenia (< 1.5 x 10(9)/L). IM patients
      had significantly lower counts of CD3, CD4, CD8, and CD3 -/ CD56+ cells, and
      significantly higher CD3 +/CD56 + lymphocyte counts. Although no significant
      differences were found between patients and controls with regard to CD19+/CD5+
      cell counts, increased CD5 + B-cell lymphocytes were observed in three IM
      patients. In one of the latter patients, Ig gene rearrangement analysis of the
      heavy chain gene demonstrated such a subpopulation to be clonal, but the patient
      did not develop features of chronic lymphoid leukemia during a 5-yr follow-up. No
      correlation was found between the patients' blood lymphocyte counts and other
      disease features. We conclude that most IM patients have absolute lymphopenia,
      decreased T cells and increased cytotoxic T cells at diagnosis, and 10% of them
      show an increased CD5 + B-cell subpopulation.

PMID- 10966170
TI  - Mutational analysis of the tumour suppressor gene MMAC1/PTEN in malignant myeloid
      disorders.
AB  - The candidate tumour suppressor gene MMAC1/PTEN located at chromosome 10q23.3 has
      been reported to be frequently mutated in a number of solid tumours. Less is
      known about its status in leukaemia. In the present study we first analysed 13
      leukaemia cell lines for mutations and homozygous deletions in MMAC1/PTEN using
      PCR and denaturing gradient gel electrophoresis (DGGE). We identified an
      intragenic deletion including MMAC1/PTEN exons 2-5 in an acute myelocytic
      leukaemia cell line, HL-60 blast, and an insertion of four nucleotides in exon 5
      in an acute monocytic leukaemia cell line, U937. Analysis of 59 patients with
      acute myeloid leukaemia (AML), 26 patients with myelodysplastic syndromes (MDS)
      and 10 patients with chronic myeloid leukaemia (CML) only revealed a polymorphic
      base substitution in codon 44 in one AML patient, suggesting that mutations in
      the MMAC1/PTEN gene are infrequent genetic aberrations in myeloid leukaemia.

PMID- 10966171
TI  - Increased risk of lymphoproliferative disorders in relatives of patients with B
      cell chronic lymphocytic leukemia: relevance of the degree of familial linkage.
AB  - We assessed the familial aggregation of chronic lymphoproliferative diseases
      (CLD) in 3962 relatives of 169 patients with B-cell chronic lymphocytic leukemia
      (B-CLL). Data collection included a self-administered questionnaire. The
      "relative risk" considered the connection between a higher incidence of CLD and
      the degree of familial linkage with the probands. The model of logistic
      regression was statistically significant (p < 0.001), with the probability of CLD
      increasing in proportion to the relationship coefficient between parents,
      siblings and children [(relationship coefficient 0.5; probability of CLD 1.85
      (C.I. 95%, range 1.1-3%)]. CLD, particularly B-CLL, were observed in first-degree
      relatives of the patients with B-CLL more often than in other relatives.

PMID- 10966173
TI  - Acute leukaemia and other secondary neoplasms in patients treated with
      conventional chemotherapy for multiple myeloma: a Finnish Leukaemia Group study.
AB  - The occurrence of acute leukaemia and other secondary neoplasms in 432 patients
      treated with conventional chemotherapy for multiple myeloma was analysed after a
      follow-up period of 11-19 yr (mean 16 yr). The number and organ-specific
      distribution of observed solid neoplasms was close to that expected in the
      general population. Non-Hodgkin's lymphoma developed in three patients (expected
      0.7, p = 0.19). Acute leukaemia was diagnosed in 14 patients with an actuarial
      risk of 9.8% at 9 yr. No further cases were diagnosed thereafter. The average
      numbers of courses (26.2 vs. 25.5) and cumulative doses of melphalan (1440 and
      1400 mg) were similar in patients with or without acute leukaemia. It seems
      possible that the advanced stage of multiple myeloma is more vulnerable to the
      leukaemogenic effect of melphalan compared with the earlier stages.

PMID- 10966172
TI  - Administration of a modified chemotherapeutic regimen containing vincristine,
      liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary
      data.
AB  - For elderly patients with multiple myeloma (MM), conventional melphalan and
      prednisone (MP) therapy has been the treatment of choice; the vincristine,
      doxorubicin and dexamethasone (VAD) regimen is preferred for younger patients who
      also receive high-dose melphalan in combination with autologous or allogeneic
      bone marrow transplantation (BMT). Although survival time is similar in both the
      MP and VAD regimens, the continuous infusion of doxorubicin which the latter
      treatment entails constitutes a disadvantage along with the 4-day hospitalization
      required. Doxorubicin also induces cardiotoxicity, particularly in the elderly. A
      modified form of VAD therapy includes liposomal doxorubicin (Caelyx) (40 mg/m2
      for 1 d) [corrected], oncovin (2 mg for 1 d) and dexamethasone 40 mg for 4 d per
      os. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is more
      efficient and has fewer side effects than conventional doxorubicin, and it can be
      administered on an outpatient basis: dexamethasone can be given orally and
      vincristine in bolus infusion. In order to estimate its efficacy and
      tolerability, we administered this regimen to 12 patients (first-line treatment
      in 6 patients, salvage therapy in 6 patients). All patients exhibited good
      tolerance to liposomal doxorubicin with no severe side effects. Eight patients
      achieved complete hematological remission and three partial response. One patient
      died before completing the treatment. In conclusion, compared to other therapies,
      this modified VAD regimen containing liposomal doxorubicin can be more easily
      administered to MM patients, without severe side effects and with increased full
      remission rates, almost similar to those with the conventional VAD treatment.

PMID- 10966174
TI  - Gene frequencies of the HPA-3 and HPA-5 platelet antigen alleles among the
      Amerindians.
AB  - Platelet antigens are of importance in several clinical situations and in
      population genetics. Data are scarce on allele frequencies in ethnic groups other
      than whites, Asians and African Americans. The frequencies of the alleles of the
      systems HPA-3 and HPA-5 were determined using the allele-specific restriction
      enzyme for five South American Amerindian populations and compared with those
      obtained for Afro-Americans, Japanese and whites from Brazil. The frequency of
      the HPA-3a allele among the Amerindians as a group did not differ from the values
      obtained for the other populations. However, differences were observed among the
      Amerindians, varying from 0.27 to 0.75, the highest frequency thus far observed
      for a population of Asian origin. Only the HPA-5a allele was found among 130
      Amerindian chromosomes. The determination of gene frequencies of the HPA systems
      in different populations allows inference of gene flows and genetic constitution
      of populations and the estimation of the risk of platelet-specific
      alloimmunization.

PMID- 10966175
TI  - Incidence, clinical features and outcome of essential thrombocythaemia in a well
      defined geographical area.
AB  - In an attempt to characterise the clinical features, incidence and outcome of
      essential thrombocythaemia (ET) we report our experience in a large unselected
      series of patients from a well defined region. All new cases of ET in the County
      of Copenhagen were registered during the period 1977-98. We identified 96 cases
      of ET, yielding an age- and sex-adjusted annual incidence rate of 0.59/100.000
      and a point-prevalence at last follow up of 11/100.000. The overall incidence
      rate was 0.31 and 1.00 per 100.000 population during the consecutive periods 1977
      89 and 1990-98, respectively, corresponding to a 3.2-fold increase. Median age at
      diagnosis was 67 yr (females 68 yr, males 66 yr, range 18-87 yr), and the female
      to male (F/M) ratio was 2.6:1. At diagnosis, 52% of the patients displayed no ET
      related symptoms and were discovered fortuitously by a routine platelet count.
      Forty-eight percent presented with thrombohaemorrhagic phenomena, of which
      microvascular disturbances of the central nervous system (CNS), extremities and
      skin were most frequently observed (23%). Compared to patients diagnosed after
      1989, patients diagnosed before 1990 had a significantly higher mean platelet
      count, white blood cell (WBC) count, lactate dehydrogenase (LDH) value and
      alkaline phosphatase value. With a median follow up of 70 months, 5-yr survival
      was 76%, significantly lower than the expected survival of an age- and sex
      matched control group (p = 0.0052). Thirty-seven patients experienced a total of
      55 thrombohaemorrhagic events during follow-up, corresponding to an incidence of
      thrombosis and microvascular disturbances or haemorrhage of 8.1% per pt-yr and
      2.5% per pt-yr, respectively. The number of patients experiencing thrombosis or
      microvascular disturbances was significantly higher among the 29 patients who
      never received acetylsalicylic acid (ASA) compared to the 67 patients who
      received ASA during follow up (45% vs. 21%; p = 0.017). This study provides
      population-based data suggesting the benefit of treatment with low-dose ASA in a
      non-selected population of patients with ET.

PMID- 10966176
TI  - Transfusion-dependent congenital dyserythropoietic anaemia with
      intraerythroblastic inclusions of a non-globin protein.
AB  - The congenital forms of dyserythropoiesis comprise a group of hereditary
      disorders characterized by ineffective erythropoiesis as the predominant
      mechanism of anaemia and morphologically abnormal erythroblasts. Up to now three
      major forms and four variants have been described. Group VII is characterized by
      dyserythropoiesis with intraerythroblastic precipitation of a non-globin protein.
      Here we described a case of dyserythropoietic anaemia presenting neonatally and
      requiring regular blood transfusions. Optical and electronic microscopy studies
      confirmed that this case was very similar to those in two previously reported
      transfusion-dependent patients with an unusual type of congenital
      dyserythropoietic anaemia.

PMID- 10966177
TI  - Autoerythrocyte sensitization (Gardner-Diamond) syndrome.
AB  - We describe the clinical presentation and course of a patient with
      autoerythrocyte sensitization (Gardner-Diamond) syndrome, and review the
      literature for similar cases. A 37-yr-old female presented with recurrent
      episodes of painful ecchymotic bruising over the anterior aspect of both thighs.
      These episodes were precipitated by emotional stress. The diagnosis was confirmed
      by induction of similar lesions by intradermal injection of the patient's own
      washed red blood cells and hemoglobin. The lesions did not recur for 6 months
      after the cause of her emotional stress was relieved. Autoerythrocyte
      sensitization (Gardner-Diamond) syndrome should be considered in the differential
      diagnosis of purpura, especially in patients with psychiatric problems.

PMID- 10966178
TI  - Heparin-induced thrombocytopenia (HIT): in vitro and in vivo cross-reactivity to
      danaparoid sodium and successful treatment with recombinant hirudin (lepirudin)

PMID- 10966179
TI  - Physiologically initiated and inhibited phantosmia: cyclic unirhinal, episodic,
      recurrent phantosmia revealed by brain fMRI.
AB  - PURPOSE: Our goal was to use functional magnetic resonance imaging (fMRI) to
      demonstrate brain activation in patients with unirhinal, episodic, recurrent
      phantosmia who induced their phantosmia by coughing, sneezing, laughing or
      vigorous nasal inhalation and expiration, and inhibited it by sleep or
      performance of a Valsalva type maneuver. METHODS: Three patients with unirhinal
      phantosmia without change in taste or smell acuity were studied by fast low angle
      shot (FLASH) MRI and by echo planar imaging (EPI). Brain activation was measured
      following memory of two tastants (salt, sweet), memory of two odorants (banana
      and peppermint), actual smell of three odors (amyl acetate, menthone, pyridine),
      memory of phantosmia (and phantageusia, where applicable), phantosmia initiated
      spontaneously or by vigorous nasal inhalation and exhalation, phantosmia after
      inhibition by Valsalva, and these stimuli before and after treatment with the
      neuroleptic thioridazine. Activation images were derived using correlation
      analysis and ratios of areas of brain activated to total brain areas were
      calculated. Total activated pixel cluster counts were also used to quantitative
      total and regional brain activation. RESULTS: Sensory-specific brain activation
      was present in each section in each patient following memory of tastants and
      odorants, actual smell of each odor and memory, and initiation of and inhibition
      of phantosmia. Activation to odor memory after phantosmia initiation was very
      robust, whereas after phantosmia inhibition it was similar to that in normal
      subjects. Brain activation to unirhinal phantosmia was bihemispheric, independent
      of whether it was left or right sided or patient handedness. While phantosmia
      memory (in the absence of initiated phantosmia) produced extremely robust brain
      activation, after initiation and inhibition of phantosmia apparent brain
      activation decreased. These changes need to be related to shifting state of
      baseline brain activation and should be interpreted to reflect increased rather
      than decreased brain activation over that of phantosmia memory alone. Treatment
      with thioridazine inhibited brain activation to all stimuli including phantosmia
      and phantageusia memory, as it did previously in patients with birhinal
      phantosmia. CONCLUSIONS: 1) Unirhinal phantosmia can be demonstrated by brain
      fMRI as can birhinal phantosmia; 2) unirhinal phantosmia can be initiated and
      inhibited by physiological maneuvers reflected by changes in fMRI brain
      activation; 3) fMRI brain activation of unirhinal phantosmia is bihemispheric and
      independent of peripheral side of phantosmia or patient handedness; 4) anterior
      frontal brain region plays a significant role in both phantosmia initiation and
      inhibition as, to some extent, do temporal brain regions; 5) activation of brain
      GABAergic systems appears to play a role in inhibition of unirhinal phantosmia;
      and 6) unirhinal phantosmia, similar to birhinal phantosmia, may reflect a type
      of maladaptive brain plasticity similar to that hypothesized to be responsible
      for phantom limb pain.

PMID- 10966180
TI  - Functional MRI of the supplementary motor area: comparison of motor and sensory
      tasks.
AB  - PURPOSE: The purpose of this work was to assess the activation of the
      supplementary motor area (SMA) during simple motor, complex motor, hot sensory,
      and touch sensory tasks. METHOD: Functional MRI (fMRI) was performed in eight
      right-handed healthy volunteers. There were four tasks: simple motor, complex
      motor, hot sensory, and touch sensory. The number of pixels and the average
      percentage change of signal intensity in the activated SMA were obtained during
      the four tasks and then compared. RESULTS: The SMA was consistently activated on
      fMRI during both motor and sensory tasks. The average number of activated pixels
      during the complex motor task was more than the number during the hot sensory
      task, but the difference was not statistically significant. The average number of
      activated pixels during the complex motor task was greater than during the simple
      motor task. The average number of activated pixels during the hot sensory task
      was greater than during the touch sensory task. The average percentage change of
      signal intensity was statistically significant between the simple motor and the
      complex motor task. The average percentage change of signal intensity was not
      statistically significant between the complex motor and the hot sensory task.
      CONCLUSION: The SMA is activated in both motor and sensory tasks. The degree of
      activation of the SMA differs according to the type of task.

PMID- 10966181
TI  - Regional cerebral blood flow distributions in normal volunteers: dynamic
      susceptibility contrast MRI compared with 99mTc-HMPAO SPECT.
AB  - PURPOSE: Relative regional cerebral blood flow (rCBF) at rest was measured in 44
      volunteers using both dynamic susceptibility contrast (DSC) MRI and (99m)Tc-HMPAO
      SPECT on the same day. METHOD: In MRI, a Gd-DTPA-BMA contrast agent bolus (0.3
      mmol/kg body wt) was monitored with a simultaneous dual FLASH pulse sequence
      (time resolution 1.5 s). MRI-based rCBF images were calculated by singular value
      decomposition-based deconvolution of the measured tissue concentration-time curve
      with an arterial input function from a small artery within the imaging slice. In
      the SPECT investigation, 900 MBq of (99m)Tc-HMPAO was injected intravenously.
      Relative rCBF in gray matter in the thalamus and in frontal white matter was
      determined. RESULTS: The ratio of relative rCBF in gray matter to relative rCBF
      in white matter was 2.21 +/- 0.57 using MRI and 2.24 +/- 0.54 using SPECT (mean
      +/- SD). CONCLUSION: Relative rCBF maps from DSC MRI and (99m)Tc-HMPAO SPECT
      showed good agreement, and the MRI-based rCBF ratio correlated with the
      corresponding SPECT-based ratio (r = 0.79, p < 0.0000006).

PMID- 10966182
TI  - Three-dimensional optical flow method for measurement of volumetric brain
      deformation from intraoperative MR images.
AB  - A three-dimensional optical flow method to measure volumetric brain deformation
      from sequential intraoperative MR images and preliminary clinical results from
      five cases are reported. Intraoperative MR images were scanned before and after
      dura opening, twice during tumor resection, and immediately after dura closure.
      The maximum cortical surface shift measured was 11 mm and subsurface shift was 4
      mm. The computed deformation field was most satisfactory when the skin was
      segmented and removed from the images before the optical flow computation.

PMID- 10966183
TI  - Radiologic assessment of metastases to the thyroid gland.
AB  - PURPOSE: We reviewed the radiologic and clinical data in patients with metastatic
      disease to the thyroid gland and assessed the role of radiologic techniques in
      this disorder. METHOD: The findings on US (n = 11), CT (n = 7), MRI (n = 6),
      palpation or US-guided fine needle aspiration (FNA) biopsy, and clinical records
      were reviewed in 11 cases of pathologically verified metastatic tumors of the
      thyroid gland. RESULTS: Five patients had palpable thyroid nodules and six had
      nonpalpable nodules discovered incidentally with imaging procedures. Three
      patients had no known malignancies at the time of diagnosis of thyroid tumors.
      Correct diagnosis was obtained in 10 of the 11 cases with FNA biopsy. Thyroid
      metastases were detected in all of the cases with US and MRI and six of the seven
      cases with CT. Thyroid metastases were solitary (n = 5) or multiple (n = 6), and
      about half of them measured <2 cm in diameter. These tumors typically had well
      defined margins and no calcification and sometimes had cystic portions. Multiple
      nodules within the same patient were radiologically quite similar to each other.
      On US, metastases appeared as hypoechoic or markedly hypoechoic areas without
      halo, on CT as low density areas, and on MRI as areas of varying signal
      intensities. Half of the metastases showed hypointensity on either T2-weighted
      images or gadolinium-enhanced T1-weighted images. The tumors involved lymph nodes
      in 10 cases and other remote organs in 5. Level I or II or parotid nodes were
      involved in six cases. CONCLUSION: These radiologic features may alert clinicians
      to a possibility of metastatic thyroid cancer. US combined with US-guided FNA
      biopsy is suitable for early diagnosis of metastases to the thyroid gland.

PMID- 10966184
TI  - Acute posttraumatic pituitary gland hemorrhage.

PMID- 10966185
TI  - Dual-slice helical CT of the thoracic aorta.
AB  - With the advent of helical CT, the capability of noninvasive imaging of the
      thoracic aorta has been enhanced considerably. In this article, we describe the
      potential of helical CT using dual-slice technology to evaluate thoracic aortic
      diseases such dissection, aneurysm, trauma, infection, inflammation,
      thromboembolic disease, and postoperative complications. Technical considerations
      for optimal CT imaging as well as limitations of helical CT are highlighted.

PMID- 10966186
TI  - Pulmonary vein and left atrial invasion by lung cancer: assessment by breath-hold
      gadolinium-enhanced three-dimensional MR angiography.
AB  - PURPOSE: The purpose of this work was to evaluate the ability of breath-hold
      gadolinium-enhanced three-dimensional (3D) MR angiography to assess the invasion
      of the pulmonary vein and the left atrium by lung cancer. METHOD: Gadolinium
      enhanced 3D MR angiography was performed in 20 consecutive patients with lung
      cancer. RESULTS: At two sites with left atrial invasion shown by MR angiography,
      associated partial resection of the left atrium was performed. At five sites with
      invasion of the proximal pulmonary vein within 1.5 cm from the left atrium on MR,
      partial resection of the left atrium was performed at one site, and the pulmonary
      vein was resected at the intrapericardial portion at three sites. At two sites
      with invasion of the proximal pulmonary vein 1.5 cm more distal to the left
      atrium, the pulmonary vein was resected at the extrapericardial portion.
      CONCLUSION: Breath-hold gadolinium-enhanced 3D MR angiography is suitable for
      assessing invasion of the pulmonary vein and the left atrium by lung cancer.

PMID- 10966187
TI  - Near drowning: thin-section CT findings in six patients.
AB  - PURPOSE: The purpose of this study was to assess the thin-section CT findings of
      near drowning in six patients. METHOD: Thin-section (1 mm collimation) CT scans
      of six patients who experienced near drowning were retrospectively analyzed. The
      CT scans were performed 0-5 days (median 1 day) after near drowning. RESULTS:
      Thin-section CT findings included bilateral patchy or diffuse areas of ground
      glass attenuation (n = 6) with geographic pattern (n = 3) and fine intralobular
      reticular opacities ("crazy-paving" appearance) (n = 3), ill-defined
      centrilobular nodules (n = 4), and air-space consolidation (n = 1). Distribution
      of ground-glass attenuation was predominantly central (n = 4) or diffuse (n = 2).
      Interstitial pulmonary emphysema and pneumomediastinum were present in two
      patients. CONCLUSION: The thin-section CT findings of near drowning consist of
      ground-glass opacities with or without associated reticular opacities and
      centrilobular nodules.

PMID- 10966188
TI  - Large cell neuroendocrine carcinoma of the lung: radiologic and pathologic
      findings.
AB  - PURPOSE: The purpose of this work was to determine the radiologic and pathologic
      findings of large cell neuroendocrine carcinoma (LCNEC). METHOD: We
      retrospectively evaluated chest radiographs, CT scans, and pathologic findings of
      five patients with pathologically confirmed LCNEC. They were confirmed by
      percutaneous needle biopsy (n = 2) and by surgery (n = 3). The average age of
      patients was 60 (51-70) years, and all five were smokers (mean 30 pack-years) and
      men. Radiologic findings were reviewed for the pattern of lesion, location, and
      associated findings by two radiologists under consensus. Pathologic findings were
      reviewed by two pathologists. RESULTS: In all five patients, tumors were
      represented as a peripherally located nodule or mass without associated secondary
      pneumonitis or distal atelectasis radiographically. On CT scan, masses were oval
      or round and well demarcated with lobulated margin in all cases, their sizes
      ranged from 2 to 5 cm, and they did not show internal calcification and necrosis.
      On contrast-enhanced CT, three cases showed moderate enhancement more than the
      chest wall muscle. Lymphadenopathy was observed in ipsilateral hilar and
      mediastinal areas in three cases. Distant metastasis to liver was noted in one
      case. One case of LCNEC was Stage IV, two were Stage IIIa, and two were Stage Ia
      at the time of diagnosis. CONCLUSION: Although the epidemiology of LCNEC is more
      similar to that of small cell carcinoma than atypical carcinoids, in its strong
      association with smoking, rapid progression, and poor prognosis, our five cases
      of LCNEC show peripherally located pulmonary nodule or mass with or without
      regional lymphadenopathy, which are findings similar to those of atypical
      carcinoids rather than small cell carcinoma.

PMID- 10966189
TI  - Evaluation of lung cancer by 99mTc-tetrofosmin SPECT: comparison with [18F]FDG
      PET.
AB  - PURPOSE: The purpose of this study was to clarify the validity of (99m)Tc
      tetrofosmin SPECT (TF-SPECT) in the evaluation of lung cancer in comparison with
      [18F]fluorodeoxyglucose ([18F]FDG-PET). METHOD: Twenty-one patients with biopsy
      proven non-small cell lung cancer were examined by both TF-SPECT (early and
      delayed images) and FDG-PET within a week of each study. Lung cancers were
      analyzed visually and semiquantitatively using the ratio of lesion to background
      counts (L/B ratio). Mediastinal lymph node metastases were analyzed only
      visually. RESULTS: Both early and delayed TF images could detect 18 of 21 lung
      cancers on visual analysis (85.7%), whereas FDG-PET could detect all the lesions
      (100%). The L/B ratio of TF-SPECT was significantly higher in delayed than in
      early images (1.79 +/- 0.55 vs. 1.56 +/- 0.40; p < 0.001). However, the L/B ratio
      of FDG-PET was 8.85 +/- 3.05, significantly higher than those of both TF images
      (p < 0.0001). In the assessment of mediastinal involvement, TF-SPECT was 40.0%
      sensitive, 100% specific, and 71.4% accurate, whereas FDG-PET was 80.0%
      sensitive, 81.8% specific, and 81.0% accurate. CONCLUSION: Although the detection
      sensitivity was far better than expected, TF-SPECT is not considered to be an
      alternative to FDG-PET in the evaluation of malignant pulmonary lesions because
      of its significantly low L/B ratio. TF-SPECT has poor sensitivity for mediastinal
      lymph node metastases and is useless for staging patients with lung cancer.

PMID- 10966190
TI  - Pedunculated bronchogenic cyst mimicking pleural lesion.
AB  - We report a rare case of a bronchogenic cyst presenting as a pleural nodule. CT
      and MRI demonstrated a well circumscribed, homogeneous lesion located on the
      pleural surface apart from the mediastinum. It was proven to be a bronchogenic
      cyst localized between the parietal and visceral pleurae and connected with the
      mediastinum only through fibrous tissue. Radiologists should be aware that a
      mediastinal bronchogenic cyst may be located apart from the mediastinum.

PMID- 10966191
TI  - Intertarsal ligaments: high resolution MRI and anatomic correlation.
AB  - High resolution MRI was performed on four cadaveric foot specimens of human feet
      to demonstrate the ligaments of the tarsal joints. Spin echo T1 images were
      obtained using a local gradient coil that produces 6 G/cm and 100 A in all three
      axes. The best views for each of the individual ligaments were determined. High
      resolution MRI potentially can demonstrate most of the intertarsal ligaments.

PMID- 10966192
TI  - Isolated tear of the teres major: a waterskiing injury.

PMID- 10966193
TI  - Transurethral resection of the prostate-related changes in the prostate gland:
      correlation of MRI and histopathology.
AB  - PURPOSE: The purpose of this work was to demonstrate signal changes of the
      prostatic urethra after transurethral resection of the prostate (TURP) on MR
      images and histopathologic correlation. METHOD: Sixty-three patients with
      prostate cancer confirmed by either TURP (Group A, 19 patients) or transrectal
      biopsy (Group B, 44 patients) were evaluated by endorectal MRI before radical
      prostatectomies. The MR images of postcurettaged prostatic urethras were
      correlated with the histopathologic features. RESULTS: On the T2-weighted images,
      a thin zone of hypointense signal surrounding the curettaged prostatic urethra
      was identified in 52.6% (10/19) of Group A patients, imaged soon after (mean 21.1
      days) TURP, but was indiscernible in Group B patients and the other Group A
      patients, imaged later after TURP (mean 49.2 days). This hypointense signal zone
      histopathologically correlates with a zone of inflammatory tissue reaction
      surrounding the widened urethra. CONCLUSION: Inflammatory tissue reaction
      surrounding curettaged prostatic urethra after TURP accounts for the presence of
      a low signal zone on T2-weighted images.

PMID- 10966194
TI  - CT and 99mTc-DMSA scintigraphy in adult acute pyelonephritis: a comparative
      study.
AB  - PURPOSE: The aim of this prospective study was to evaluate the relative value of
      CT and (99m)Tc-DMSA scintigraphy in the diagnosis of acute pyelonephritis (APN)
      in adult patients suspected of having urinary tract infection. METHOD: The study
      was conducted in 36 patients presenting with symptoms suggestive of urinary tract
      infection. Plain B-mode sonography, CT with contrast medium, and (99m)Tc-DMSA
      scintigraphy of the kidneys were performed in all patients. Both CT and (99m)Tc
      DMSA scintigraphy were performed within 72 h after admission. RESULTS: Twelve
      patients with clinical and biological signs of urinary tract infection had no CT
      or (99m)Tc-DMSA scintigraphy abnormalities. Among these patients, lower urinary
      tract infection was found in 10 patients and 2 patients had ureteral obstruction.
      In the 24 remaining patients, the diagnosis of APN was made. Among these
      patients, a correlation was found between CT and (99m)Tc-DMSA scintigraphy in 11
      cases. In two cases, both examinations were normal, and in nine cases, both were
      abnormal. In 11 cases of the 13 remaining patients, abnormal CT was found with
      normal (99m)Tc-DMSA scintigraphy, whereas the 2 last cases had normal CT and
      abnormal (99m)Tc-DMSA scintigraphy results. In two cases, bilateral lesions found
      on CT manifested as unilateral abnormalities on (99m)Tc-DMSA scintigraphy images.
      CONCLUSION: The diagnosis of APN in adult patients is based on clinical
      presentation and biological findings. Few studies have compared (99m)Tc-DMSA
      scintigraphy with CT in the detection of parenchymal involvement in APN. We
      conclude that CT is more accurate than (99m)Tc-DMSA scintigraphy in the detection
      of APN lesions in adult patients.

PMID- 10966195
TI  - Yolk sac tumor of the ovary: radiologic-pathologic correlation in four cases.
AB  - We report the radiologic and pathologic features of yolk sac tumor (endodermal
      sinus tumor) of the ovary in four patients. Yolk sac tumors were shown as well
      enhancing solid tumors on both CT and MR studies and were associated with
      prominent signal voids on MRI. A hypervascular nature was confirmed on
      microscopic studies. Areas of hemorrhage were another common characteristic.
      These imaging findings seem to have an important implication for the diagnosis of
      this tumor.

PMID- 10966196
TI  - MR appearance of adenomatoid tumor of the uterus.
AB  - Reports on the radiological findings of adenomatoid tumor of the uterus are rare,
      and preoperative diagnosis is very difficult. To our knowledge, there have been
      no reports concerning the MR findings of adenomatoid tumor of the uterus. We
      report two cases of uterine adenomatoid tumor that showed the characteristic
      features of leiomyoma on MR images.

PMID- 10966197
TI  - Volumetric measurement of renal cysts and parenchyma using MRI: phantoms and
      patients with polycystic kidney disease.
AB  - We have developed an MR method to measure the volumes of renal cysts and
      parenchyma in patients with polycystic kidney disease. Phantoms were designed to
      simulate polycystic kidneys. Four patients were recruited. MR scans were
      performed on the phantoms and patients. A stereology technique was applied for
      image segmentation and volume measurement. Volumetric measurement of renal cysts
      and parenchyma was accurate in phantom studies and reliable in both phantom and
      patient studies in these limited examples.

PMID- 10966198
TI  - MRI of malignant fibrous histiocytoma of the spermatic cord.

PMID- 10966200
TI  - Dysplastic nodules and hepatocellular carcinoma: sensitivity of digital
      subtraction hepatic arteriography with whole liver explant correlation.
AB  - PURPOSE: The purpose of this work was to determine the sensitivity of hepatic
      digital subtraction arteriography (DSA) for the detection of hepatocellular
      carcinoma (HCC) and dysplastic nodules (DNs) when compared with pathological
      findings from whole liver explants. METHOD: Twenty-one patients 30-72 years old
      (mean 54 years) with cirrhosis and known or clinically suspected HCC (20 prior to
      chemoembolization) underwent hepatic DSA with subsequent transplantation within
      80 days (mean 32 days). The prospective DSA report was compared with pathologic
      findings from explanted livers. RESULTS: Overall, DSA detected 31 of 95 HCC
      lesions for a sensitivity of 33%. Of these 31 lesions, 28 were hypervascular and
      3 were hypovascular. DSA detected all six HCCs measuring >5 cm, all six HCCs
      measuring 3-5 cm, and all five HCCs 2-3 cm, resulting in a sensitivity of 100%
      (17/17) for HCC >2 cm. DSA detected 7 of 18 HCCs measuring 1-2 cm (sensitivity
      39%) and 7 of 60 HCCs < or =1 cm (sensitivity 12%). Overall sensitivity for DSA
      in detection of HCC < or =2 cm was 18% (14/78 lesions). None of 17 DNs (0.2-1.5
      cm in size) was identified on DSA. CONCLUSION: DSA is insensitive to small HCC (<
      or =2 cm), carcinomatosis arising within nodules, and DN.

PMID- 10966199
TI  - Mesenchymal tumors of the pancreas: CT findings.
AB  - This article reviews the CT imaging features of the most frequent mesenchymal
      tumors of the pancreas and stresses important distinctive patterns that may help
      distinguish specific entities. Various neoplasms (lymphangioma, lipoma, teratoma,
      pancreatoblastoma, schwannoma, neurofibroma, lymphoma, and sarcoma) are reviewed,
      with key differential points (structure, fatty and water densities,
      calcification, pattern of contrast enhancement, vascularization, and necrotic or
      regressive changes) emphasized. In addition, epithelial tumors are considered in
      the differential diagnosis.

PMID- 10966201
TI  - Cystic dystrophy of the duodenal wall in the heterotopic pancreas:
      radiopathological correlations.
AB  - PURPOSE: The purpose of this work was to correlate the CT features of cystic
      dystrophy in heterotopic pancreas (CDHP) with pathological features. METHODS:
      Patients were selected from 190 patients who underwent pancreatico-duodenectomy
      over a 10 year period in our institution. CT findings were retrospectively
      analyzed in 20 cases and correlated with pathological findings. RESULTS: Lesions
      were found to be located in the inner part of the second portion of the duodenum
      in all except one case. In all cases, the duodenal wall was thickened, both at CT
      and at histopathological examination, and moderate to strong contrast enhancement
      of the duodenal wall was noted at CT in all cases but one. Cysts were multiple in
      all cases. No heterotopic pancreas was identified with CT. Inflammatory changes
      with or without enlarged nodes were detected on CT in 15 of 20 cases. Chronic
      pancreatitis was present in 10 cases at pathology, including 5 cases with
      calcifications. The radiopathological correlation was excellent for all criteria
      but two: the size of the cysts and the extent of pyloric involvement. CONCLUSION:
      In patients with CDHP, CT features correlate well with pathological results.
      Multiple cysts located in an enlarged duodenal wall with postcontrast enhancement
      and inflammatory changes are strongly suggestive of CDHP.

PMID- 10966202
TI  - Digital image fusion of CT and PET data sets--clinical value in abdominal/pelvic
      malignancies.
AB  - PURPOSE: We investigated the clinical relevance of digital image fusion of CT and
      2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET)
      studies in patients with suspected abdominal and/or pelvic metastasis. METHOD:
      Nineteen patients with suspected residual/recurrent malignancies underwent CT and
      [18F]FDG PET studies of the abdomen and/or pelvis. The data sets of both
      modalities were fused on a digital workstation by automatic adaptation of the
      pixel size and the slice thickness. Different body positions were corrected by
      semiautomatic adaptation of the body axes. The fused images were reconstructed in
      sagittal, coronal, and axial planes. RESULTS: Good spatial correlation between
      both modalities was achieved in all patients. Image fusion improved the spatial
      allocation of pathologically increased [18F]FDG uptake in 7 of 35 lesions (20%).
      CONCLUSION: This work suggests that digital image fusion of CT and [18F]FDG PET
      data sets improves the anatomical localization of foci with increased [18F]FDG
      enhancement of the retroperitoneum and the abdominal/pelvic wall, respectively.

PMID- 10966203
TI  - Early radiation effects on the liver demonstrated on superparamegnetic iron oxide
      enhanced T1-weighted MRI.
AB  - Early radiation-induced liver injury during radiotherapy detected by a
      particulate reticuloendothelial MR contrast agent (superparamagnetic iron oxide;
      SPIO) is described in a patient with cholangiocarcinoma. The irradiated hepatic
      parenchyma appeared as a heterogeneous, less decreased signal intensity area than
      the nonirradiated area on MR images after SPIO administration. Resultant
      differences in signal intensity were better visualized on SPIO-enhanced T1
      weighted images than SPIO-enhanced T2-weighted images, although SPIO-enhanced T2*
      weighted fast field echo imaging was the most sensitive.

PMID- 10966204
TI  - Huge biliary cystadenoma mimicking cholecystic lymphangioma in subhepatic space.
AB  - Biliary cystadenoma is a rare cystic neoplasm and constitutes only 5% of all
      intrahepatic cysts of biliary origin. We report a case of a 44-year-old woman
      with huge biliary cystadenoma in the subhepatic space, mimicking a cholecystic
      lymphangioma. Findings of various imaging modalities including reconstructed CT
      image are presented and correlated with surgical and pathologic findings.

PMID- 10966205
TI  - MR appearance of the small intestinal cavernous hemangioma.

PMID- 10966206
TI  - MRI of an isolated traumatic perforation of the gallbladder.

PMID- 10966207
TI  - The nomenclature and sectional imaging anatomy II: ventral spinal ligaments.
AB  - This paper is the second in a series of three that organizes the complex anatomy
      of the cervical, thoracic, and lumbar spinal ligaments. It describes and
      colorcodes the anatomy and nomenclature of the ventral ligaments. A prior article
      has described the dorsal ligaments, and a future article will illustrate the
      capsular joints and minor spinal ligaments.

PMID- 10966208
TI  - Giant cell myocarditis: most fatal of autoimmune diseases.
AB  - OBJECTIVE: To increase awareness of giant cell myocarditis (GCM), its
      pathogenesis, and treatment. METHODS: Review of relevant publications from the
      English-language literature. RESULTS: GCM is a rare, frequently fatal
      inflammatory disorder of cardiac muscle of unknown origin, characterized by
      widespread degeneration and necrosis of myocardial fibers.Congestive heart
      failure and ventricular tachycardia are common clinical manifestations. GCM
      occurs primarily in previously healthy adults, although it is frequently
      associated with various systemic diseases, primarily of autoimmune causes. The
      inflammatory infiltrate is characterized by the presence of multinucleated giant
      cells and is distinct from cardiac sarcoidosis. Animal models of GCM are similar
      to models of other autoimmune disorders such as rheumatoid arthritis. The
      prognosis, which is poor despite partial responsiveness to immunosuppressive
      medications, is improved with cardiac transplantation. CONCLUSIONS: The clinical
      and immunopathogenetic similarities with classical rheumatologic diseases, the
      differential diagnosis with sarcoidosis and other inflammatory conditions, and
      the use of standard immunosuppressive medications make GCM a disease process that
      should be added to the rheumatologist's expertise.

PMID- 10966209
TI  - Erythrocyte sedimentation rate and C-reactive protein in the evaluation of
      disease activity and severity in polymyalgia rheumatica: a prospective follow-up
      study.
AB  - OBJECTIVE: To determine the frequency and clinical features of patients with
      polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at
      diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive
      protein (CRP) and ESR in the assessment of PMR activity. METHODS: A prospective
      follow-up study on 177 consecutive patients meeting the criteria for PMR
      diagnosed over a 5-year period was conducted in two Italian secondary referral
      centers of rheumatology. At diagnosis and during follow-up, ESR (Westergren
      method) and CRP (nephelometry) were measured in all patients. Phenotypic analysis
      of lymphocyte subpopulations was performed on 78 PMR patients at diagnosis. A two
      color technique using the association of specific monoclonal antibodies was
      applied. A control group consisting of 18 healthy adults older than 60 years was
      matched for age and sex with the PMR patients. RESULTS: Ten of 177 (6%) patients
      had normal ESR values at diagnosis (< or = 30 mm/h). Patients with normal ESR
      were predominantly men and had lower CRP levels; systemic signs and symptoms were
      more frequent in patients with higher ESR. The percentages of circulating CD8+
      cells were similar in the two groups. CRP values at diagnosis were normal in only
      2 of 177 (1%) patients. CRP values were elevated in 9 of 10 patients with normal
      ESR at diagnosis. Twenty-five episodes of relapse/recurrence with normal ESR
      occurred in 17 patients. CRP was high in 62% of these episodes. Results of
      univariate analysis indicated that the 10th percentile for ESR (40 mm/h) and the
      70th percentile for CRP (7.8 mg/dL) values at diagnosis were the best cutoff
      points that discriminate between patients with and without relapse/recurrence.
      Cox proportional hazards modeling showed that ESR greater than 40 mm/h and CRP
      greater than 7.8 mg/dL at diagnosis were the two variables that independently
      increased the risk of relapse/recurrence. However, the relative risk related to
      ESR was twice than that related to CRP (4.9 vs 2.1). CONCLUSION: PMR with a
      normal ESR at diagnosis was infrequent in our study compared with previous
      studies. ESR was a superior predictor of relapse than CRP. However, CRP was a
      more sensitive indicator of current disease activity.

PMID- 10966210
TI  - The role of B-mode ultrasonography and electron beam computed tomography in
      evaluation of Takayasu's arteritis: a study of 43 patients.
AB  - OBJECTIVES: To evaluate the capacity of B-Mode ultrasonography (B-Mode US) and
      electron-beam computed tomography (EBCT) to detect arterial changes in Takayasu's
      arteritis. METHODS: EBCT angiography of the thoracoabdominal aorta and pulmonary
      artery, and B-mode US of large superficial arteries (common carotid, subclavian,
      and common femoral arteries) were performed prospectively in 43 consecutive
      patients with established Takayasu's arteritis. The arterial wall thickness was
      measured, and lumen changes (stenosis, aneurysm) were noted. RESULTS: The
      combined results of B-Mode US and EBCT examinations showed that every patient had
      at least one abnormality at the studied sites. The median score of abnormal sites
      was 7. The most frequent lesion was a characteristic long, homogeneous,
      circumferential thickening, visualized in 52% of examined sites and in all
      patients but one (98%). Stenosis was detected by US and by EBCT, respectively, in
      44% and 32% of patients, and aneurysm in 0.4% and 68%. CONCLUSIONS: In Takayasu's
      arteritis, B-Mode US and EBCT was able to visualize the classical caliber
      abnormalities (stenosis, aneurysm) and, in contrast to angiography, to depict
      vessel wall thickening, a major pathologic feature of the disease. Both these
      safe techniques seem more useful than angiography to characterize and map the
      vascular lesions of Takayasu's arteritis.

PMID- 10966211
TI  - Sarcoidosis and systemic vasculitis.
AB  - BACKGROUND: Systemic vasculitis is an unusual complication of sarcoidosis. Over a
      10-year period, the authors have provided care for six patients who had features
      of both sarcoidosis and vasculitis. Vasculitis could not be attributed to other
      causes. OBJECTIVES: To report six patients (five children) who had sarcoidosis
      and systemic vasculitis and compare our experience with previous literature. To
      better delineate the clinical spectrum of sarcoid vasculitis and its response to
      therapy. METHODS: Retrospective analysis and a Medline literature review of
      sarcoid and concurrent vasculitis from 1966. RESULTS: Our six patients had
      systemic illnesses that included fever, peripheral adenopathy, hilar adenopathy,
      rash, pulmonary parenchymal disease, musculoskeletal symptoms, and scleritis or
      iridocyclitis. Biopsies revealed features compatible with the diagnosis of
      sarcoidosis or necrotizing sarcoid granulomata in either skin, lymph node, lung,
      synovium, bone, bone marrow, liver, trachea, or sclera. Arteriography showed
      features of large vessel vasculitis in three patients, all of whom were African
      American, whereas patients with small vessel vasculitis were white. Prior reports
      of sarcoid and vasculitis included 14 adults, of whom half had predominantly
      small vessel disease, and half had medium- or large-sized vessel disease. Eight
      previously reported children included seven with primarily large vessel sarcoid
      vasculitis. Racial background was noted in 15 reported cases and included whites
      (6), African Americans (5), and Asians (4). Among the authors' six patients, four
      improved when treated with prednisone alone. However, relapses occurred when the
      drug was tapered or withdrawn. CONCLUSIONS: Sarcoidosis may be complicated by
      systemic vasculitis that can affect small- to large-caliber vessels. Sarcoid
      vasculitis can mimic hypersensitivity vasculitis, polyarteritis nodosa,
      microscopic polyangiitis, or Takayasu's arteritis. African American and Asian
      patients are disproportionately represented among cases with large vessel
      involvement. Corticosteroid and cytotoxic therapy is palliative for all forms of
      sarcoid vasculitis. However, relapses and morbidity from disease and treatment is
      common.

PMID- 10966212
TI  - Fibromyalgia syndrome in men.
AB  - OBJECTIVE: Fibromyalgia syndrome (FMS) is uncommon in men and data on its
      characteristics and severity are limited. The current study was undertaken to
      determine whether the clinical characteristics and the spectrum of this disorder
      are similar in men and women. METHODS: Forty men with FMS were matched with 40
      women by age and educational level. All subjects were asked about the presence
      and severity (assessed by visual analog scale) of FMS symptoms; a count of 18
      tender points was conducted by thumb palpation, and tenderness thresholds were
      measured by dolorimetry. Psychological status was assessed by the anxiety and
      depression subscales of the revised Arthritis Impact Measurement Scales. Quality
      of life was evaluated by two scales, QOL-16 and SF-36, and physical function was
      measured by the Fibromyalgia Impact Questionnaire. RESULTS: Men with FMS reported
      more severe symptoms than women, decreased physical function, and lower quality
      of life. Women had lower tender thresholds than men; however their mean point
      counts were similar. CONCLUSION: Although FMS is uncommon in men, its health
      outcome in our study population was worse than in women. Further studies in
      larger samples and in diverse ethnocultural populations are needed to confirm
      this observation.

PMID- 10966213
TI  - Magnetic resonance imaging in rheumatic disorders of the spine and sacroiliac
      joints.
AB  - OBJECTIVE: To review the value of magnetic resonance imaging (MRI) in diagnosis
      and evaluation of rheumatic diseases of the spine and sacroiliac joints. METHODS:
      A review of the literature on MRI of the spine and sacroiliac joints in
      rheumatoid arthritis (RA), ankylosing spondylitis (AS), infectious
      spondylodiscitis, infection of the sacroiliac joint (SIJ), gout, calcium
      pyrophosphate deposition disease, nontraumatic vertebral compression fractures,
      insufficiency fracture of the sacrum, avascular necrosis of the vertebral body,
      sarcoidosis, and Paget's disease was performed. The reports were obtained from a
      Medline search. RESULTS: In RA, AS, and crystal deposition disease, synovial
      tissue, atlantoaxial and subaxial subluxations, crystal deposition, and
      neurologic compromise can be adequately diagnosed with MRI of the cervical spine.
      Studies on MRI of SIJs in AS indicate that MRI enables early diagnosis of
      sacroiliitis. In most cases of infectious spondylodiscitis, avascular necrosis of
      the vertebral body, nontraumatic vertebral compression fractures, and
      insufficiency fractures of the sacrum characteristic findings on MRI suggest the
      correct diagnosis. Moreover, soft tissue abnormalities and neurologic compromise
      can be visualized. In infection of the SIJ, MRI shows findings suggesting an
      inflammatory process. In Paget's disease, MRI does not provide additional
      information as compared with plain radiography (PR) or computed tomography (CT).
      CONCLUSION: In evaluation of spinal and SIJ abnormalities in many rheumatic
      diseases, MRI, in addition to PR, can replace conventional tomography, CT, and
      myelography. Moreover, MRI can visualize soft tissue abnormalities and neurologic
      compromise without use of intrathecal contrast.

PMID- 10966214
TI  - SAPHO: rare or just not recognized?
AB  - OBJECTIVE: The SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis)
      syndrome describes an association between musculoskeletal disorders, in
      particular hyperostosis involving the bones and joints of the anterior chest
      wall, and various dermatologic conditions. It has been reported in Europe and
      Japan, but no Australian series have been published. We describe the clinical,
      laboratory, and radiographic features of a group of patients with the SAPHO
      syndrome and compare this with the literature. METHODS: We performed a
      retrospective review of patients seen in our department between 1990 and 1998 who
      met the proposed diagnostic criteria for SAPHO. Information regarding age, sex,
      disease duration, skeletal site(s) of disease, presence of skin disease, previous
      treatment, and response to treatment was collected. Laboratory tests were
      reviewed, as was all available radiology and bone scintigraphy. RESULTS: Six
      women with a mean age of 40 years fulfilled the criteria for SAPHO. The skeletal
      manifestations were similar to those reported in the literature, with
      hyperostosis of the anterior chest wall being the central feature. Cervical spine
      and pubic bone were other sites of involvement, whereas sacroiliitis and
      peripheral joint synovitis were not seen. Skin disease was less frequent in our
      population than has been reported in other series. Nonsteroidal anti-inflammatory
      drugs were frequently prescribed as first-line treatment but had limited
      efficacy. Intravenous pamidronate was administered to two patients, resulting in
      complete resolution of pain in one patient and 50% reduction in pain in the
      other. CONCLUSIONS: The SAPHO syndrome may be underrecognized as the skin
      manifestations in our patients were mild or absent. Although optimal treatment
      for these patients remains unclear, it is important to make the diagnosis of
      SAPHO to avoid unnecessary investigations and treatment.

PMID- 10966215
TI  - Gyrodactylus poeciliae n. sp. and G. milleri n. sp. (Monogenea: Gyrodactylidae)
      from Poecilia caucana (Steindachner) in Venezuela.
AB  - Two new species of Gyrodactylus are described from the South American live
      bearing fish Poecilia caucana from Venezuela. Gyrodactylus poeciliae n. sp. is
      characterised by conspicuous ventral bar processes and by marginal hooks in which
      the tips are barely curved. Morphologically, the species resembles G.
      bullatarudis and G. costaricensis, and its relationship to the former was
      confirmed by sequencing the Internal Transcribed Spacers (ITS-1 and ITS-2) and
      the 5.8S ribosomal gene of the ribosomal DNA. Gyrodactylus milleri n. sp. was
      characterised by large, sharply angled marginal hook sickles in which the tips
      overhang the toes. This species resembled most closely G. turnbulli from guppies.
      These descriptions confirm the occurrence of G. turnbulli and G. bullatarudis
      like gyrodactylids on a range of South American poeciliid fishes.

PMID- 10966216
TI  - Digeneans from intertidal molluscs of SW Iceland.
AB  - The fauna of digenean daughter-sporocysts, rediae, cercariae and metacercariae
      infecting molluscs Littorina spp., Onoba aculeus. Nucella lapillus and Epheria
      vincta has been studied in the Skerjafjordur and Grindavik regions of SW Iceland.
      In total, intramolluscan stages of 19 digenean species were recorded; 14 of them
      are new for Iceland and one of them, a microphallid named Cercaria islandica I,
      was unknown. A description of this new microphallid cercaria is provided. In
      addition, the identification and separation of the intramolluscan stages of some
      microphallid, renicolid and echinostomatid species are discussed. Consideration
      is given to difficulties encountered when identifying digenean species found on
      the coasts of European countries. Problems have arisen largely because larval and
      adult stages have been described and named independently and in isolation,
      synonyms are common and many "definitive" descriptions are inadequate or
      incomplete.

PMID- 10966217
TI  - Asterocheres crinoidicola n. sp., a copepod (Siphonostomatoida: Asterocheridae)
      parasitic on crinoids in Belize.
AB  - A new species of siphonostomatoid copepod, Asterocheres crinoidicola, is
      parasitic on two closely related comasterid crinoids (Nemaster grandis and
      Davidaster rubiginosus) in Belize, Central America. An unusually long terminal
      prolongation of the third segment of the endopod of leg 1 distinguishes this
      species from all congeners. This is the first report of a copepod parasitic on a
      crinoid in the Caribbean.

PMID- 10966218
TI  - Tetrameres (Gynaecophila) aspicula n. sp. (Nematoda: Tetrameridae), a
      proventricular parasite of the white-faced ibis Plegadis chihi in Argentina.
AB  - Tetrameres (Gynaecophila) aspicula n. sp. is described from the proventriculus of
      the white-faced ibis Plegadis chihi (Vieillot) (Ciconiiformes, Threskiornithidae)
      from Argentina. The new species is characterised by the absence of spicules, by
      possessing two ventral rows of extremely small spines in males, extending along
      the second half of body length, and by the tiny, very feebly developed
      postcloacal papillae. T. (G.) aspicula n. sp. is compared to the remainder of the
      species in the subgenus as well as to other species of Tetrameres which lack or
      possess feebly developed spines. The absence of spicules is a character shared
      with two other species in the genus, T. (G.) gynaecophila and T. (G.) deccani,
      from which the new species differs in body size, the arrangement of caudal
      papillae and the somatic spination in males. A pair of somatic papillae,
      previously unreported in species of this genus, was found just on or ventral to
      the lateral line at various regions of the body length. The homology of these
      structures to other paired somatic papillae described in nematodes is discussed.

PMID- 10966219
TI  - Longidorus camelliae n. sp. (Nematoda: Longidoridae) associated with ornamental
      cultivars of Camellia japonica L. growing in a nursery at Fuyang, Zhejiang
      Province, eastern China.
AB  - A description is provided of Longidorus camelliae n. sp., a bisexual species
      associated with ornamental cultivars of Camellia japonica L. growing in Fuyang,
      Zhejiang Province, eastern China. The species is characterised by its small body
      length (1.83-3.54 mm), narrow (6-10 microm), anteriorly flattened, continuous
      head region, non-bilobed amphidial pouches, medium odontostyle length (80-91,
      microm) and elongate, conoid tail (32-39 microm; c' = 1.1-1.4). Males are
      characterised by having short spicules (44-48 microm) and a row of seven
      supplements. The species has only three juvenile development stages.

PMID- 10966220
TI  - Paramaritremopsis solielangi n. sp. and Microphallus kinsellai n. sp. (Digenea:
      Microphallidae) parasites of Charadrii (Aves) of Belize (Central America).
AB  - The authors describe and illustrate two trematodes from Belize (Central America):
      Paramaritremopsis solielangi n. sp. from the small intestine of Arenaria
      interpres is characterised by a body length of 478 microm, two short and pre
      acetabular caeca, part of the uterus in close association with the cirrus-sac and
      left caecum, vitelline glands in the shape of a horseshoe, a short pre-ovarian
      cirrus-sac containing a long, cylindrical, voluminous and unarmed cirrus (size
      when evaginated: 150 x 20-30 microm) and Microphallus kinsellai n. sp. from the
      caeca of Actitis macularia characterised by a body length of 370 microm and a
      phallus which is 30 microm in diameter and asymmetrical (basically a pad with a
      moderately developed accessory lobe) and a straight ejaculatory canal.
      Levinseniella carteretensis is another microphallid recovered from Arenaria
      interpres. The term of "phallus" is proposed to name the male copulatory organ
      which characterizes the Microphallinae.

PMID- 10966221
TI  - Two new species of Duplicibothrium Williams & Campbell, 1978 (Tetraphyllidea:
      Serendipidae) from the Pacific cownose ray Rhinoptera steindachneri.
AB  - Two new tetraphyllidean species, Duplicihothrium caircae n. sp. and D. paulum n.
      sp., are described from Pacific cownose rays Rhinoptera steindachneri collected
      from the Gulf of California. D. cairae n. sp. differs from the only other known
      species in this genus, D. minutum, in its possession of two posteriorly
      bifurcating longitudinal septa on each bothridium and having a greater number of
      loculi per bothridium, wider bothridia and a greater number of segments per worm.
      D. paulum n. sp. differs from the above two species in being shorter, having two
      continuous longitudinal septa on each bothridium, rather than posteriorly
      bifurcating or absent longitudinal septa, having a greater number of loculi per
      bothridium and having fewer segments per worm. The generic diagnosis of
      Duplicibothrium is amended to reflect the inclusion of the two new species.
      Species of Duplicibothrium appear to be restricted to host species of the genus
      Rhinoptera. Systematic information gained from the study of these two new species
      supports the monophyly of the tetraphyllidean family Serendipidae and suggests
      that Duplicibothrium shares a phylogenetic heritage with species in the genera
      Glyphobothrium and Serendip, taxa that are also parasitic in cownose rays.
      Evidence for a phylogenetic relationship between serendipid species and species
      of Dioecotaenia is discussed, as are potential molluscan hosts for cestode
      species in Duplicibothrium and Dioecotaenia.

PMID- 10966223
TI  - Parasites as indicators of human biology and evolution.

PMID- 10966222
TI  - The status of Petalocotyle Ozaki, 1934 (Digenea: Gyliauchenidae), including the
      description of two new species from acanthurid fishes in Queensland, Australia.
AB  - The status of Petalocotyle Ozaki, 1934 within the Gyliauchenidae Goto &
      Matsudaira, 1918 is reviewed. Two new species, P. adenometra from Prionurus
      microlepidotus (Amity Point, Queensland, Australia) and P. diverticulata from
      Acanthurus nigrofiuscus and A. lineatus (Heron Island, Queensland, Australia),
      are described. The body plan of Petalocotyle conforms to that of members of the
      Gyliauchenidae (oral sucker absent, well-developed pharynx, complex oesophagus
      and characteristic male terminal genitalia), indicating justifiable inclusion in
      this family. A new diagnosis is given for the genus, such that Petalocotyle is
      now identified by the presence of an anterior, protuberant ventral sucker, long
      caeca, a large, sigmoid cirrus-sac containing a coiled ejaculatory duct, and an
      extensive vitellarium. We suggest that, of all the known genera of gyliauchenids,
      Petalocotyle may most closely resemble the 'archaetypal gyliauchenid', that is,
      it may be placed basally within the radiation of the Gyliauchenidae. However,
      derived characters, like diverticula in the reproductive system, indicate that
      some characters of individual members of Petalocotyle may be considered advanced
      and do not reflect an archaetypal condition. Parallels in the structure of the
      male and female genitalia of Robphildollfusium Paggi & Orecchia, 1963 and
      Petalocotyle, along with the shared morphology of the digestive tract, indicate
      possible phylogenetic links between the two genera. This affinity is difficult to
      infer using morphology alone and recommend that Robphildollfusium remain detached
      from the Gyliauchenidae.

PMID- 10966224
TI  - Simplified phenotypic tests for identification of Acinetobacter spp. and their
      antimicrobial susceptibility status.
AB  - Acinetobacter spp. have been found to be responsible for an increasing number of
      nosocomial infections. During a 16-month period, 22 patients hospitalised mainly
      in the respiratory intensive care unit (RICU), paediatric and other medical wards
      were investigated either for infection or colonisation by Acinetobacter spp. Of
      the 45 isolates of Acinetobacter detected among the total of 425 non-fermenters
      encountered, 24 representative isolates were selected for extended phenotypic
      identification. Four environmental isolates were also included in the study.
      These 28 isolates were typed by biotyping and antibiotyping, which helped in
      delineating the Acinetobacter spp. into 12 phenotypes and two distinct
      antibiotypes respectively. A sudden increase of cases of acinetobacter infection
      suggested that three outbreaks during the study period were due to phenotypes 1
      and 2 of A. calcoaceticus-A. baumannii complex (Acb). Strains of Acb-complex
      showed multiple drug resistance and were sensitive only to netilmicin. A
      comparatively high proportion of resistance to amikacin (48%) was also detected
      among these strains by the agar dilution method. The RICU environment was
      recognised as an important reservoir for the resistant outbreak strain (Acb-1)
      which was probably leading to persistent colonisation and recurrent infections.

PMID- 10966225
TI  - Detection and speciation of Cryptosporidium spp. in environmental water samples
      by immunomagnetic separation, PCR and endonuclease restriction.
AB  - Current methods for the detection of Cryptosporidium oocysts in water samples are
      both time-consuming and subject to variation in sensitivity. A genus-specific PCR
      assay was designed for the specific amplification of a 552-bp region of the 18S
      rRNA gene. Postamplification endonuclease restriction generated unique digest
      patterns that enabled differentiation between the three species, C. muris, C.
      baileyi and C. parvum, the major human pathogen. Theoretical restriction profiles
      for other Cryptosporidium species were also predicted. The assay routinely
      detected 10 oocysts in 10-ml purified oocyst preparations, but sensitivity was
      found to be 10(3)-10(4) -fold lower in environmental water samples. The use of
      Chelex resin and an immunomagnetic separation procedure overcame this inhibition.
      This provided detection levels of 10(1)-10(3) oocysts, depending on water
      turbidity. Rapid and sensitive pathogen detection methods are essential for the
      water industry. The results of this study demonstrate that PCR has the potential
      to improve current detection capabilities greatly by differentiating the major
      human pathogens from non-pathogenic species. This will greatly facilitate a
      closer examination of the epidemiology of this important pathogen.

PMID- 10966226
TI  - Comparison of resin-containing BACTEC Plus Aerobic/F* medium with conventional
      methods for culture of normally sterile body fluids.
AB  - The sensitivity of culture in Bactec Plus Aerobic/F* culture vials of body fluids
      from adult patients at a university hospital was compared with that of
      conventional culture methods, including enrichment in Schaedler broth. Previous
      antibiotic therapy was recorded at the time of sampling. Analysis of culture
      results took account of the clinical significance of isolates and impact on
      therapy. Of 336 specimens evaluated, 81 (24%) yielded positive cultures, of which
      50 cultures (15%) were considered to be clinically significant (yielding 71
      isolates) and 31 (9%) were considered contaminated. Of the 71 pathogens, 16 (23%)
      were isolated in the Bactec system only, whereas 13 (18%) grew in conventional
      media only; 12 of the latter were strict anaerobes. Among clinically significant
      positive specimens, 19 (38%) were from patients receiving antibiotic therapy. In
      27 cases (8% of all specimens and 54% of significantly positive cultures), the
      isolation of a pathogen led to modification of therapy. Overall, culture in the
      Bactec system showed higher sensitivity for the isolation of aerobic micro
      organisms than Schaedler broth. Most of the difference was due to a better
      recovery of Streptococcaceae. Additional pathogens found only in resin-containing
      Bactec media led to 30% of all culture-influenced modifications of empirical
      therapy. These data confirm that culture of normally sterile body fluids
      frequently yields results that are useful for guiding therapy. Although more
      costly than standard enrichment broth, the resin-containing Bactec Plus
      Aerobic/F* vial can be advantageous for culture of aerobic pathogens from these
      specimens, particularly in patients receiving antibiotic therapy.

PMID- 10966227
TI  - Genotypic characterisation of endemic VanA Enterococcus faecium strains isolated
      in a paediatric hospital.
AB  - A total of 36 vancomycin-resistant Enterococcus faecium isolates obtained from 30
      patients during a 28-month period in a paediatric university hospital was
      analysed by pulsed-field gel electrophoresis (PFGE) combined with Southern
      hybridisation of a vanA-specific DNA probe. All the isolates hybridised with the
      vanA probe. Seventeen different PFGE patterns and 11 PFGE subtypes were
      identified among the 36 clinical isolates, and the size of probe-positive bands
      ranged from c. 30 to 300 kb. These data are consistent with an increase in the
      overall genomic diversity of vancomycin-resistant E. faecium isolates during the
      study period. Two periods were distinguished. The prevalence of a single clone in
      the initial period suggested transmission between patients in three wards. During
      the following period, multiple genotypes of vancomycin-resistant E. faecium were
      identified, indicative of multiple introductions or the dissemination of
      resistance genes by recombinant transposition.

PMID- 10966228
TI  - Mechanisms of chloride secretion induced by thermostable direct haemolysin of
      Vibrio parahaemolyticus in human colonic tissue and a human intestinal epithelial
      cell line.
AB  - Thermostable direct haemolysin (TDH) produced by Vibrio parahaemolyticus is
      thought to play an important role in the severe diarrhoea caused by this
      organism. This study investigated the enterotoxicity of TDH for human intestinal
      cells. Addition of TDH to the mucosal side of human colonic tissue in Ussing
      chambers caused increased short circuit currents (Isc), a process that was
      inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), an
      inhibitor of Ca2+ -activated chloride (Cl-) channels. With human colonic
      epithelial (Caco-2) cells, high Isc and intracellular Ca2+ concentrations
      ([Ca2+]in) were detected after the addition of TDH to the apical side of the cell
      monolayer. The Isc decreased with the addition of DIDS, but not with
      glybenclamide, 5-nitro-2-(3-phenylpropylamino) benzoic acid, or gadolinium
      chloride. No Isc increase with TDH was observed when the Cl- in the medium was
      replaced by gluconate or when Ca2+ was depleted. Similarly, TDH did not raise
      [Ca2+]in after depletion of extracellular Ca2+. R7, a mutant form of TDH, reduced
      the effects of TDH on Isc and [Ca2+]in, as did protein kinase C (PKC) inhibitors.
      Thus, TDH increases Cl- secretion in human colonic epithelial cells, apparently
      through mechanisms involving cell binding and Ca2+ influx, followed by elevation
      of [Ca2+]in associated with PKC phosphorylation.

PMID- 10966229
TI  - Haemolysin-deficient variants of Streptococcus pyogenes and S. dysgalactiae
      subsp. equisimilis may be overlooked as aetiological agents of pharyngitis.
AB  - Variants of large colony beta-haemolytic Lancefield group A, C and G streptococci
      that are non-haemolytic or alpha-haemolytic on sheep blood agar have been
      detected in clinical specimens due to their enhanced haemolytic activity when
      grown on a new selective and differential blood agar medium containing colistin,
      nalidixic acid and pH 7.5-adjusted PIPES buffer (CNA-P). The large colony
      Lancefield group C and G isolates were identified as Streptococcus dysgalactiae
      subsp. equisimilis by API 20 Strep classification and 16S rDNA profiling. The
      haemolytic activity of these variants on various blood agar media, including CNA
      P, was closely similar to that of known streptolysin S-defective mutants of S.
      pyogenes and was blocked by addition of cholesterol, a specific inhibitor of the
      streptolysin O family of haemolysins. As haemolysin variants could be detected in
      large numbers in cultures from patients with clinical symptoms of pharyngitis it
      is suggested that they may function as primary pathogens in such infections. The
      high frequency with which haemolysin variants were isolated from clinical
      specimens during a 3-month trial (3%, 13% and 10%, respectively, of group A, C
      and G streptococcal isolates) indicated that a substantial proportion of
      streptococcal infections may go undetected if only conventional sheep blood agar
      media are used in clinical laboratories for the detection of beta-haemolytic
      streptococci. As haemolysin variants have been implicated in the development of
      serious streptococcal sequelae, further investigation of the full extent of their
      contribution to streptococcal disease is indicated.

PMID- 10966230
TI  - Profiling of bacterial flora in gastric biopsies from patients with Helicobacter
      pylori-associated gastritis and histologically normal control individuals by
      temperature gradient gel electrophoresis and 16S rDNA sequence analysis.
AB  - The aim of this study was to establish bacterial profiles in gastric biopsy
      specimens from patients with Helicobacter pylori-associated gastritis by means of
      temporal temperature gradient gel electrophoresis (TTGE) of PCR-amplified 16S
      rDNA fragments. Specimens from eight patients with asymptomatic gastritis and
      five histologically normal controls revealed a Helicobacter-specific band in the
      TTGE profile with increased amounts of Helicobacter-specific DNA in the biopsies
      from most of the gastritis patients. DNA from other genera including
      Enterococcus, Pseudomonas, Streptococcus, Staphylococcus and Stomatococcus was
      also found in the stomach. In the absence of gastric inflammation, Helicobacter
      spp. appeared to be part of a complex, presumably indigenous microbial flora
      found in the biopsy specimens from the stomach.

PMID- 10966231
TI  - Unidentified serogroups of enteropathogenic Escherichia coli (EPEC) associated
      with diarrhoea in infants in Londrina, Parana, Brazil.
AB  - Digoxigenin-labelled DNA probes were used to characterise enteropathogenic
      Escherichia coli (EPEC) isolated in Londrina (Brazil) from faeces samples of 102
      children with diarrhoea, and the results were compared with those obtained by
      serogrouping and adherence to HEp-2 cells. The probes employed detect the gene
      coding EPEC adherence factor (EAF) and the virulence genes for bundle-forming
      pilus (bfp) and entero-attaching-effacing (eae) factor. Twenty-one isolates
      hybridised with at least one probe, and 11 of them were classified as typical
      EPEC because they hybridised with all three probes, showed a pattern of localised
      adherence (LA) and carried no genes for enterotoxins (ST and LT) or invasion as
      detected by PCR. Six of the typical EPEC strains belonged to the classical
      serotype 0119:H6 and one to O111:H6; O antigens could not be determined in four
      strains with antisera against 01-0173. All typical EPEC strains carried a 70-MDa
      plasmid plus two other large plasmids. These data showed that typical EPEC
      virulence traits may be found in strains not belonging to classical
      serogroups/serotypes and that molecular identification is required for studying
      the epidemiology of diarrhoea in children.

PMID- 10966232
TI  - Aerobic and anaerobic microbiology in intra-abdominal infections associated with
      diverticulitis.
AB  - The aerobic and anaerobic microbiology of intra-abdominal infections associated
      with diverticulitis was studied in 110 specimens from the peritoneal cavity after
      intestinal perforation and in 22 specimens from abdominal abscesses. Anaerobic
      bacteria only were isolated from 17 (15%) of the peritoneal specimens, aerobic
      bacteria only from 12 (11%) and mixed aerobic and anaerobic flora from 81 (74%).
      A total of 339 bacterial isolates was detected in peritoneal cultures (3.1 per
      specimen), comprising 155 aerobes (1.4 per specimen) and 184 anaerobes (1.7 per
      specimen). Anaerobic bacteria only were isolated in 4 (18%) abscesses, aerobes
      alone in one (5%) and mixed aerobic and anaerobic flora in 17 (77%). A total of
      72 bacterial isolates (3.3 per specimen) was detected in abdominal abscesses - 35
      aerobes (1.6 per specimen) and 37 aerobes (1.7 per specimen). The predominant
      aerobic and facultative bacteria in abdominal infections were Escherichia coli
      and Streptococcus spp. The most frequently isolated anaerobes were Bacteroides
      spp. (B. fragilis group), Peptostreptococcus, Clostridium and Fusobacterium spp.

PMID- 10966233
TI  - Antifungal activity of ibuprofen alone and in combination with fluconazole
      against Candida species.
AB  - Ibuprofen, a non-steroidal anti-inflammatory drug, exhibited antimicrobial
      activity against Candida albicans and non-albicans strains. At 10 mg/ml,
      ibuprofen showed a rapid cidal activity against exponential growth phase C.
      albicans, accompanied by rapid and extensive leakage of intracellular K+,
      permeation to propidium iodide, lysis of spheroplasts and severe membrane
      ultrastructural alterations. These results indicate that the killing of Candida
      cells is due to direct damage to the cytoplasmic membrane. At 5 mg/ml, ibuprofen
      inhibited growth; however, it did not kill the yeasts and did not directly affect
      the cytoplasmic membrane. Evaluation of yeast metabolic vitality with the
      fluorescent probe FUN-1 showed that growth inhibition induced by the fungistatic
      drug concentration was due to metabolic alterations. The combination of ibuprofen
      with fluconazole resulted in synergic activity with eight of the 12 Candida
      strains studied, including four of the five fluconazole-resistant strains. The
      MICs of fluconazole for the fluconazole-resistant strains decreased 2-128-fold
      when the drug was associated with ibuprofen. When in combination with
      fluconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains
      studied. These results point to the practicability of using ibuprofen, alone or
      in combination with azoles, in the treatment of candidosis, particularly when
      applied topically, taking advantage of the drug's antifungal and anti
      inflammatory properties.

PMID- 10966234
TI  - The bactericidal activity of gemifloxacin (SB-265805).
AB  - The bactericidal activity and mechanisms of action of the new fluoroquinolone
      gemifloxacin were investigated against the laboratory strains Escherichia coli
      KL16, Staphylococcus aureus E3T and Streptococcus pneumoniae C3LN4. Gemifloxacin
      was found to be highly bactericidal against these bacteria, producing a biphasic
      dose-response curve typical of the fluoroquinolones. This novel fluoroquinolone
      was more bactericidal than all other fluoroquinolones so far tested
      (ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, levofloxacin, clinafloxacin,
      trovafloxacin, DV-7751 and sitafloxacin) against S. aureus and was more
      bactericidal than most other fluoroquinolones against E. coli or Str. pneumoniae.
      These data show gemifloxacin to be an improved member of the fluoroquinolone
      class of antibacterial agents.

PMID- 10966236
TI  - Interleukin-10 gene transfer improves the survival rate of mice inoculated with
      Escherichia coli.
AB  - OBJECTIVE: To determine whether administration of recombinant adenovirus vectors
      encoding the interleukin (IL)-10 protein (AxCAmIL-10) decreases the mortality of
      septic mice. DESIGN: Prospective, randomized, controlled study. SETTING:
      University research laboratory. SUBJECTS: Adult male C57B/6 mice. INTERVENTIONS:
      Untreated mice and those injected intraperitoneally with 1 x 10(9) pfu of AxCAmIL
      10 were used as control 1 and 2, respectively. Double-capsules without
      Escherichia coli were intraperitoneally embedded in another group (control 3).
      Mice embedded with capsules containing E. coli were divided into the following
      groups: simultaneous administration of 0.5 mL of saline (group 1), and
      administration of AxCAmIL-10 3 hrs before embedding (group 2) or 1 hr after
      embedding (group 3). Histopathologic changes together with expression
      concentrations of IL-10 and tumor necrosis factor (TNF) in various organs and
      plasma were examined 18 hrs after each treatment. Observation periods were 5-8
      days. Survival rates were compared between these groups. MEASUREMENTS AND MAIN
      RESULTS: The plasma IL-10 concentrations were increased in control 2, group 2,
      and group 3 but not in control 1, control 3, or group 1, indicating successful
      adenovirus gene transfer. Plasma TNF values were significantly reduced in groups
      2 and 3 as compared with group 1, with no significant differences in endotoxin
      concentrations. Survival rates were significantly better in groups 2 and 3 than
      in group 1 (p < .05). CONCLUSION: These findings suggested that IL-10 has a
      favorable effect on survival of septic mice via inhibition of TNF production or
      endotoxin stimulation.

PMID- 10966235
TI  - Clonal spread of an invasive strain of Haemophilus influenzae type b among
      nursery contacts accompanied by a high carriage rate of non-disease-associated
      strains.
AB  - Haemophilus influenza carriage was examined in unvaccinated nursery contacts of a
      patient with H. influenzae type b (Hib) meningitis and isolates were typed by
      pulsed-field gel electrophoresis (PFGE). Nasopharyngeal isolates were classified
      into eight PFGE patterns. Seven Hib carriers were found among 15 nursery
      contacts. The isolates from the carriers showed a PFGE pattern identical to that
      of the meningitis strain. The carrier rate of non-disease-associated strains was
      also high (47%, 7 of 15). This study suggests that the clonal spread of invasive
      (serotype b) H. influenzae strains is accompanied by a high carriage rate of non
      disease-associated strains.

PMID- 10966237
TI  - Myocardial effects of repeated electrical defibrillations in the isolated
      fibrillating rat heart.
AB  - OBJECTIVE: Although substantial myocardial cell injury has been reported after
      high-energy electrical defibrillation, only minimal injury with transient
      functional defects seems to develop at energy levels not exceeding those required
      to reverse ventricular fibrillation. Because multiple electrical shocks are often
      delivered in clinical settings during attempts to reverse ventricular
      fibrillation, we investigated the effects of repetitive shocks on
      postresuscitation myocardial dysfunction by using an isolated rat heart model of
      ventricular fibrillation. DESIGN: Prospective and randomized. SETTING:
      Cardiopulmonary resuscitation research laboratory. SUBJECTS: Twenty-seven Sprague
      Dawley rats. INTERVENTIONS: Hearts were harvested and perfused at a constant flow
      of 10 mL/min by using a modified Krebs-Henseleit solution equilibrated with 95%
      oxygen and 5% CO2. Ventricular fibrillation (VF) was induced by a 0.05-mA current
      delivered to the right ventricular endocardium and the perfusate flow was
      stopped. After 10 mins, the perfusate flow was resumed at 20% of baseline flow
      and maintained for 15 additional minutes before returning to baseline flow after
      25 mins of VF (VF25 mins). Twenty-seven hearts were randomized to receive from
      VF22 mins to VF25 mins either 0 epicardial shocks, 6 epicardial shocks, or 12
      epicardial shocks. MEASUREMENTS AND MAIN RESULTS: Isovolumic indices of left
      ventricular function were obtained by using a latex balloon advanced through the
      mitral valve into the ventricular cavity. After defibrillation, indices of
      contractile function rapidly returned to baseline without differences among
      groups. The isovolumic end-diastolic pressure, however, remained elevated
      throughout the postresuscitation interval. A left shift of the diastolic pressure
      volume curves without changes in their slope was observed at 10 mins after
      resuscitation with partial return to baseline by 30 mins postresuscitation. The
      shifts were significantly greater in hearts that received 12 shocks. CONCLUSIONS:
      These findings indicate that repetitive low-energy electrical shocks do not
      accentuate postischemic systolic dysfunction in the isolated fibrillating rat
      heart but adversely affect postischemic diastolic dysfunction by reducing the
      unstressed left ventricular end-diastolic volume.

PMID- 10966238
TI  - Aminoethyl-isothiourea, a nitric oxide synthase inhibitor and oxygen radical
      scavenger, improves survival and counteracts hemodynamic deterioration in a
      porcine model of streptococcal shock.
AB  - OBJECTIVE: To test the effect of a continuous infusion of the nitric oxide (NO)
      synthase (S) inhibitor aminoethyl-isothiourea (AE-ITU) on survival time,
      hemodynamics, and oxygen transport in a porcine model of live group A
      streptococcal (GAS) sepsis. Furthermore, to examine the role of endothelin-1,
      histamine, and reactive oxygen species (ROS) in streptococcal shock. DESIGN:
      Prospective, randomized trial. SETTING: Laboratory at a university hospital.
      SUBJECTS: Twenty-eight pigs with an average weight of 25 kg. INTERVENTIONS:
      Sixteen animals received a continuous infusion of live Streptococcus pyogenes 1.3
      x 10(10) colony forming units/hr: eight received fluids only, and the other eight
      received an intravenous infusion of AE-ITU 10 mg/kg/hr starting 30 mins before
      the GAS challenge. Six control pigs received AE-ITU 10 mg/kg/hr iv for 5 hrs.
      Another six animals received half the dose of GAS over 5 hrs. MEASUREMENTS AND
      MAIN RESULTS: GAS infusion caused a rapid increase in pulmonary, hepatic, and
      systemic vascular resistance, followed by hypotension with a 90% lethality at 4
      hrs. Treatment with AE-ITU increased 4-hr survival in septic animals from 1/8 to
      8/8 and 5-hr survival from 0/8 to 5/8, prevented hypotension, and increased urine
      output. AE-ITU attenuated the decrease in cardiac output, liver blood flow, and
      oxygen delivery, and hepatic arterial blood flow as a fraction of cardiac output
      increased (all p < .05). Plasma nitrate/nitrite levels decreased in all animals.
      Inducible NOS and endothelial constitutive NOS activities in liver, gut, and lung
      were not increased during sepsis, nor were they decreased after AE-ITU. Plasma
      levels of endothelin-1 and methylhistamine increased in all septic animals and
      were not modified by AE-ITU. AE-ITU prevented the increase in monocyte ROS
      production caused by GAS. In control animals, AE-ITU caused an increase in mean
      arterial pressure, liver blood flow, and oxygen delivery. CONCLUSIONS: In this
      model of porcine GAS-induced septic shock, which was not associated with enhanced
      NO production, infusion of the NOS inhibitor AE-ITU prolonged survival, prevented
      hypotension, and improved cardiac contractility, organ perfusion, and tissue
      oxygenation. These beneficial effects of AE-ITU might be a result of the combined
      effect of ROS scavenging and modulation of local NO production, thus improving
      the balance of vasodilator and vasoconstrictor forces and reducing oxidative
      stress.

PMID- 10966239
TI  - Hemodynamic and gas exchange response to inhaled nitric oxide and prone
      positioning in acute respiratory distress syndrome patients.
AB  - OBJECTIVE: To analyze the single effect and the interaction of prone position and
      inhaled nitric oxide (iNO) on lung function and hemodynamic variables. DESIGN: 2
      x 2 factorial trial. SETTING: Department of intensive care medicine at a
      university hospital. PATIENTS: Fourteen patients on volume-controlled mechanical
      ventilation for acute respiratory distress syndrome (ARDS). INTERVENTION: Four
      experimental conditions, each one characterized by the patient's position (supine
      or prone) with iNO or without iNO. MEASUREMENTS AND RESULTS: Hemodynamic and gas
      exchange data were collected for each experimental condition. PaO2 was increased
      both by positioning (p < .01) and iNO (p < .01); iNO caused also a reduction in
      venous admixture (p < .01), pulmonary artery pressure (p < .01), and pulmonary
      vascular resistance index (p < .05). We could not demonstrate any significant
      interaction between the two treatments. The average effect of prone positioning
      was the same both with and without iNO, whereas the average effect of iNO was the
      same in both the prone and the supine position. CONCLUSION: In the studied acute
      respiratory distress syndrome patients the average effects of iNO and positioning
      on oxygenation were additive and no interaction could be shown. A strategy
      including both treatments could warrant the best improvement in oxygenation, and
      should take into account the individual response to each treatment and the
      possible combination of the two.

PMID- 10966240
TI  - A lipid A analog, E5531, blocks the endotoxin response in human volunteers with
      experimental endotoxemia.
AB  - BACKGROUND: Endotoxin (lipopolysaccharide [LPS]) has been associated with sepsis
      and the high mortality rate seen in septic shock. The administration of a small
      amount of LPS to healthy subjects produces a mild syndrome qualitatively similar
      to that seen in clinical sepsis. We used this model to test the efficacy of an
      endotoxin antagonist, E5531, in blocking this LPS-induced syndrome. METHODS: In a
      placebo-controlled, double-blind study, we randomly assigned 32 healthy
      volunteers to four sequential groups (100, 250, 500, or 1000 microg of E5531).
      Each group of eight subjects (six assigned to E5531, two assigned to placebo)
      received a 30-min intravenous infusion of study drug. LPS (4 ng/kg) was
      administered to all subjects as an intravenous bolus in the contralateral arm at
      the midpoint of the infusion. Symptoms, signs, laboratory values, and
      hemodynamics (by echocardiogram) were evaluated at prospectively defined times.
      RESULTS: In subjects receiving placebo, LPS caused headache, nausea, chills, and
      myalgias. E5531 led to a dose-dependent decrease in these symptoms that was
      statistically significant (p < .05) except for myalgias. The signs of endotoxemia
      (fever, tachycardia, and hypotension) were consistently inhibited at the three
      higher doses (250, 500, and 1000 microg, p < .05). Tumor necrosis factor-alpha
      and interleukin-6 blood levels were both lower in those who received E5531 (p <
      .0001). The C-reactive protein level and white blood cell count response were
      decreased at all doses (p < .0001). The hyperdynamic cardiovascular state (high
      cardiac index and low systemic vascular resistance) associated with endotoxin
      challenge was significantly inhibited at the higher doses of E5531. CONCLUSIONS:
      E5531 blocks the symptoms and signs and cytokine, white blood cell count, C
      reactive protein, and cardiovascular response seen in experimental endotoxemia.
      This agent is a potent inhibitor of endotoxin challenge in humans and may be of
      benefit in the prevention or treatment of sepsis and septic shock.

PMID- 10966241
TI  - Effects of helium-oxygen on intrinsic positive end-expiratory pressure in
      intubated and mechanically ventilated patients with severe chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To test the hypothesis that replacing 70:30 nitrogen: oxygen (Air-O2)
      with 70:30 helium:oxygen (He-O2) can decrease dynamic hyperinflation ("intrinsic"
      positive end-expiratory pressure) in mechanically ventilated patients with
      chronic obstructive pulmonary disease (COPD), and to document the consequences of
      such an effect on arterial blood gases and hemodynamics. DESIGN: Prospective,
      interventional study. SETTING: Medical intensive care unit, university tertiary
      care center. PATIENTS: Twenty-three intubated, sedated, paralyzed, and
      mechanically ventilated patients with COPD enrolled within 36 hrs after
      intubation. INTERVENTIONS: Measurements were taken at the following time points,
      all with the same ventilator settings: a) baseline; b) after 45 mins with He-O2;
      c) 45 mins after return to Air-O2. The results were then compared to those
      obtained in a test lung model using the same ventilator settings. MAIN RESULTS
      (MEAN + SD): Trapped lung volume and intrinsic positive end-expiratory pressure
      decreased during He-O2 ventilation (215+/-125 mL vs. 99+/-15 mL and 9+/-2.5 cm
      H2O vs. 5+/-2.7 cm H2O, respectively; p < .05). Likewise, peak and mean airway
      pressures declined with He-O2 (30+/-5 cm H2O vs. 25+/-6 cm H2O and 8+/-2 cm H2O
      vs. 7+/-2 cm H2O, respectively; p < .05). These parameters all rose to their
      baseline values on return to Air-O2 (p < .05 vs. values during He-O2). These
      results were in accordance with those obtained in the test lung model. There was
      no modification of arterial blood gases, heart rate, or mean systemic arterial
      blood pressure. In 12/23 patients, a pulmonary artery catheter was in place,
      allowing hemodynamic measurements and venous admixture calculations. Switching to
      He-O2 and back to Air-O2 had no effect on pulmonary artery pressures, right and
      left ventricular filling pressures, cardiac output, pulmonary and systemic
      vascular resistance, or venous admixture. CONCLUSION: In mechanically ventilated
      COPD patients with intrinsic positive end-expiratory pressure, the use of He-O2
      can markedly reduce trapped lung volume, intrinsic positive end-expiratory
      pressure, and peak and mean airway pressures. No effect was noted on hemodynamics
      or arterial blood gases. He-O2 might prove beneficial in this setting to reduce
      the risk of barotrauma, as well as to improve hemodynamics and gas exchange in
      patients with very high levels of intrinsic positive end-expiratory pressure.

PMID- 10966242
TI  - Effects of perfusion pressure on tissue perfusion in septic shock.
AB  - OBJECTIVE: To measure the effects of increasing mean arterial pressure (MAP) on
      systemic oxygen metabolism and regional tissue perfusion in septic shock. DESIGN:
      Prospective study. SETTING: Medical and surgical intensive care units of a
      tertiary care teaching hospital. PATIENTS: Ten patients with the diagnosis of
      septic shock who required pressor agents to maintain a MAP > or = 60 mm Hg after
      fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) > or = 12 mm
      Hg. INTERVENTIONS: Norepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in
      10 patients with septic shock. MEASUREMENTS AND MAIN RESULTS: At each level of
      MAP, hemodynamic parameters (heart rate, PAOP, cardiac index, left ventricular
      stroke work index, and systemic vascular resistance index), metabolic parameters
      (oxygen delivery, oxygen consumption, arterial lactate), and regional perfusion
      parameters (gastric mucosal Pco2, skin capillary blood flow and red blood cell
      velocity, urine output) were measured. Increasing the MAP from 65 to 85 mm Hg
      with norepinephrine resulted in increases in cardiac index from 4.7+/-0.5
      L/min/m2 to 5.5+/-0.6 L/min/m2 (p < 0.03). Arterial lactate was 3.1+/-0.9 mEq/L
      at a MAP of 65 mm Hg and 3.0+/-0.9 mEq/L at 85 mm Hg (NS). The gradient between
      arterial P(CO2) and gastric intramucosal Pco2 was 13+/-3 mm Hg (1.7+/-0.4 kPa) at
      a MAP of 65 mm Hg and 16+/-3 at 85 mm Hg (2.1+/-0.4 kPa) (NS). Urine output at 65
      mm Hg was 49+/-18 mL/hr and was 43+/-13 mL/hr at 85 mm Hg (NS). As the MAP was
      raised, there were no significant changes in skin capillary blood flow or red
      blood cell velocity. CONCLUSIONS: Increasing the MAP from 65 mm Hg to 85 mm Hg
      with norepinephrine does not significantly affect systemic oxygen metabolism,
      skin microcirculatory blood flow, urine output, or splanchnic perfusion.

PMID- 10966243
TI  - Tumor necrosis factor gene polymorphism and septic shock in surgical infection.
AB  - OBJECTIVES: To evaluate the relationship of the genotype distribution of the
      tumor necrosis factor (TNF)-alpha polymorphism with regard to the plasma TNF
      alpha concentration and the development of septic shock as well as mortality of
      infected patients in a surgical intensive care unit (SICU). DESIGN: A total of
      112 postoperative critically ill infected patients were prospectively enrolled.
      SETTING: SICU of a tertiary university-affiliated medical center. PATIENTS:
      Patients who were consecutively admitted to the SICU because of surgical
      infection with sepsis. INTERVENTION: Blood sampling. MEASUREMENTS AND MAIN
      RESULTS: Blood sample was obtained 24 hrs after intensive care unit (ICU)
      admission or within 2 hrs after the onset of septic shock to determine the plasma
      TNF-alpha level and to analyze the genotype of the biallelic polymorphism of the
      TNF-alpha. RESULTS: The allele frequency of the TNF2 in our infected ICU patients
      was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic
      shock during their ICU stay. Patients carrying the TNF2 allele were not more
      likely to develop septic shock, nor did they have a higher mortality rate. In the
      patients with septic shock, those carrying the TNF2 allele had a significantly
      higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%,
      p < .05). In those who developed septic shock, the TNF2 allele was significantly
      associated with higher TNF levels. CONCLUSION: In patients admitted to SICU with
      surgical infection, the frequency of TNF2 allele was higher than in the general
      population. SICU patients with TNF2 allele did not show a higher incidence of
      developing septic shock, nor was there a higher baseline TNF-alpha level after
      infection. However, once septic shock had developed, the mortality rate was
      higher in those patients carrying the TNF2 allele.

PMID- 10966244
TI  - Impact of quantitative invasive diagnostic techniques in the management and
      outcome of mechanically ventilated patients with suspected pneumonia.
AB  - OBJECTIVE: To assess how data obtained by invasive diagnostic techniques may
      affect management and outcome of patients with suspected ventilator-associated
      pneumonia (VAP), in comparison with noninvasive qualitative techniques. DESIGN:
      Prospective study. SETTING: An 18-bed medical and surgical intensive care unit.
      PATIENTS: A total of 91 patients suspected of having VAP were randomized into two
      groups. In group A (n = 45), quantitative cultures obtained by either
      bronchoscopic or nonbronchoscopic techniques were performed, whereas in group B
      (n = 43), patients were treated based on clinical judgment and nonquantitative
      tracheal aspirates cultures. Three patients were excluded because of the absence
      of follow-up. RESULTS: In patients with positive cultures, therapeutic changes
      were made in 20 patients. In four patients (three from group A and one from group
      B, p = NS), initial empirical antibiotic treatment was modified because the
      isolated microorganisms were not susceptible (all of them had late-onset
      pneumonia). The isolated organisms responsible for antibiotic modifications were
      methicillin-resistant Staphylococcus aureus (three patients) and Pseudomonas
      aeruginosa (one patient). In three patients, the antimicrobial therapy was
      considered inappropriate because the isolated microorganisms were multiresistant
      and treated with only one effective antibiotic. In 13 patients (ten from group A
      and three from group B, p < .05), treatment was changed to select a narrower
      spectrum antibiotic. No therapeutic modifications were made in patients with
      negative cultures based on the results of quantitative cultures. The overall
      mortality was 22.2% in group A and 20.9% in group B. There were no differences in
      intensive care unit stay or days of mechanical ventilation (23.67+/-3.15 vs.
      22.42+/-3.01 and 19.99+/-2.88 vs. 19.24+/-3.04, respectively). CONCLUSIONS: In
      our study population, the routine use of quantitative invasive diagnostic tools
      is not justified in the setting of ventilated patients clinically suspected of
      having nosocomial pneumonia.

PMID- 10966245
TI  - Long-term survival and health status after prolonged mechanical ventilation after
      cardiac surgery.
AB  - OBJECTIVE: To determine hospital mortality, weaning from mechanical ventilation,
      long-term survival, and functional health status in patients receiving > or =7
      days of mechanical ventilation after cardiac surgery. DESIGN: Retrospective chart
      review and prospective patient interviews. SETTING: A university-affiliated,
      tertiary care medical center. PATIENTS: A total of 124 patients that received >
      or =7 days of mechanical ventilation after cardiac surgery. INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: Hospital and long-term death, liberation from mechanical
      ventilation, and functional health status. MEASUREMENTS AND MAIN RESULTS: A total
      of 19 (15%) patients died in hospital. Of the 105 survivors, 104 (99%) were
      completely weaned from mechanical ventilation. Patients who died in the hospital
      were more likely to have had a preoperative stroke or to have a new postoperative
      stroke, more likely to have postoperative renal failure, and less likely to have
      chronic obstructive pulmonary disease. Kaplan-Meier survival was 59% at 5 yrs and
      expected median survival was 6.2 yrs. Patients who died anytime after discharge
      were more likely to have preoperative renal dysfunction or stroke, took longer to
      be weaned from mechanical ventilation and to be discharged, and were more likely
      to have postoperative complications such as stroke or renal dysfunction. Also,
      they were more likely to be too debilitated to walk or eat. By multivariate
      analysis, admitting creatinine, aortic valve surgery, number of ventilator days,
      and discharged on tube feedings remained significant predictors of mortality. A
      total of 40 of 53 survivors were interviewed. Participants were similar to
      nonparticipants (p > .10 for all characteristics). A few (16%) had limitations of
      their activities of daily living (eating, dressing, bathing), and most had
      limitations of moderate activity (60%) and vigorous activity (94%). Only 36%
      could climb stairs or walk uphill without limitations, 54% could walk a block,
      and 41% had no limitations in house or job work. Half the participants had no
      body pain; 38% had moderate and 4% severe pain. Most (59%) described their
      general health as good to excellent. Only 10% said it was poor. CONCLUSION:
      Patients' chances of being liberated from mechanical ventilation are excellent.
      Their long-term survival and health status are good.

PMID- 10966246
TI  - Kinetics and dynamics of lorazepam during and after continuous intravenous
      infusion.
AB  - OBJECTIVE: To evaluate the kinetics and dynamics of lorazepam during
      administration as a bolus plus an infusion, using electroencephalography as a
      pharmacodynamic end point. METHODS: Nine volunteers received a 2-mg bolus loading
      dose of lorazepam, coincident with the start of a 2 microg/kg/hr zero-order
      infusion. The infusion was stopped after 4 hrs. Plasma lorazepam concentrations
      and electroencephalographic activity in the 13- to 30-Hz range were monitored for
      24 hrs. RESULTS: The bolus-plus-infusion scheme rapidly produced plasma lorazepam
      concentrations that were close to those predicted to be achieved at true steady
      state. Mean kinetic values for lorazepam were as follows: volume of distribution,
      126 L; elimination half-life, 13.8 hrs; and clearance, 109 mL/min.
      Electroencephalographic effects were maximal 0.5 hr after the loading dose, were
      maintained essentially constant during infusion, and then declined in parallel
      with plasma concentrations after the infusion was terminated. There was no
      evidence of tolerance. Plots of pharmacodynamic electroencephalographic effect
      vs. plasma lorazepam concentration demonstrated counterclockwise hysteresis,
      consistent with an effect-site equilibration delay. This was incorporated into a
      kinetic-dynamic model in which hypothetical effect-site concentration was related
      to pharmacodynamic electroencephalographic effect via the sigmoid Emax model. The
      analysis yielded the following mean estimates: maximum electroencephalographic
      effect, 12.7% over baseline; 50% effective concentration, 13.1 ng/mL; and effect
      site equilibration half-life, 8.8 mins. CONCLUSION: Despite the delay in effect
      onset, continuous infusion of lorazepam, preceded by a bolus loading dose,
      produces a relatively constant sedative effect on the central nervous system,
      which can be utilized in the context of critical care medicine.

PMID- 10966247
TI  - Effect of norepinephrine on the outcome of septic shock.
AB  - OBJECTIVE: Despite increasingly sophisticated critical care, the mortality of
      septic shock remains elevated. Accordingly, care remains supportive. Volume
      resuscitation combined with vasopressor support remains the standard of care as
      adjuvant therapy, and many consider dopamine to be the pressor of choice. Because
      of fear of excessive vasoconstriction, norepinephrine is considered to be
      deleterious. The present study was designed to identify factors associated with
      outcome in a cohort of septic shock patients. Special attention was paid to
      hemodynamic management and to the choice of vasopressor used, to determine
      whether the use of norepinephrine was associated with increased mortality.
      DESIGN: Prospective, observational, cohort study. SETTING: Intensive care unit of
      a university hospital. PATIENTS: Ninety-seven adult patients with septic shock.
      MEASUREMENTS AND MAIN RESULTS: Data from these patients were examined to select
      variables independently and significantly associated with outcome during the
      hospital stay. Nineteen clinical, biological, and hemodynamic variables were
      collected at study entry or during the first 48-72 hrs and analyzed for each
      patient. A stepwise logistic regression analysis and a model building strategy
      were used to identify variables independently and significantly associated with
      outcome. The overall hospital mortality was 73% (71 patients). Five variables
      were significantly associated with outcome. One factor was strongly associated
      with a favorable outcome: the use of norepinephrine as part of the hemodynamic
      support of the patients. The 57 patients who were treated with norepinephrine had
      significantly lower hospital mortality (62% vs. 82%, p < .001; relative risk =
      0.68; 95% confidence interval = 0.54-0.87) than the 40 patients treated with
      vasopressors other than norepinephrine (high-dose dopamine and/or epinephrine).
      Four variables were associated with a poor outcome and significantly higher
      hospital mortality: pneumonia as a cause of septic shock (82% vs. 61%, p < .03;
      relative risk = 1.47; 95% confidence interval = 1.07-1.77), organ system failure
      index < or = 3 (92% vs. 60%, p < .001; relative risk = 1.47; 95% confidence
      interval = 1.17-1.82), low urine output at entry to the study (88% vs. 60%, p <
      .01; relative risk = 1.44; 95% confidence interval = 1.06-1.87), and admission
      blood lactate concentration > 4 mmol/L (91% vs. 63%, p < .01; relative risk =
      1.60; 95% confidence interval = 1.27-1.84). CONCLUSIONS: Our results indicate
      that the use of norepinephrine as part of hemodynamic management may influence
      outcome favorably in septic shock patients. The data contradict the notion that
      norepinephrine potentiates end-organ hypoperfusion, thereby contributing to
      increased mortality. However, the present study suffers from some limitation
      because of its nonrandomized, open-label, observational design. Hence, a
      randomized clinical trial is needed to clearly establish that norepinephrine
      improves mortality of patients with septic shock, as compared with high-dose
      dopamine or epinephrine. Pneumonia as the cause of septic shock, high blood
      lactate concentration, and low urine output on admission are strong indicators of
      a poor prognosis. Multiple organ failure is confirmed as a reliable predictor of
      mortality in septic patients.

PMID- 10966248
TI  - Early role of neutrophil L-selectin in posttraumatic acute lung injury.
AB  - OBJECTIVE: To investigate whether early numerical and functional changes in
      circulating neutrophils and expression of neutrophil L-selectin and soluble L
      selectin are related to the subsequent development of posttraumatic acute lung
      injury (ALI), the systemic inflammatory response syndrome, sepsis, and organ
      failure. DESIGN: Prospective study of whole blood and plasma samples to assess
      numerical and functional changes in circulating neutrophils and in soluble L
      selectin. SETTING: The emergency department of a university hospital. PATIENTS: A
      total of 147 patients admitted to the resuscitation room after trauma were
      compared with 69 control subjects. Ten patients developed ALI. LABORATORY
      ANALYSIS: Flow cytometry of whole blood and ELISA of plasma. RESULTS: Total
      leukocyte and neutrophil counts, expression of L-selectin, and the ratio of
      neutrophil to plasma L-selectin increased with injury and were highest in those
      who developed ALI. Soluble L-selectin decreased with injury severity and was
      lowest in those who developed ALI. CONCLUSIONS: Early changes in the average
      expression of L-selectin per cell do not correlate with the development of
      subsequent posttraumatic ALI. However, the development of ALI is related to the
      total expression of L-selectin in the neutrophil mass, and the most striking
      association is in those with lower concentrations of plasma L-selectin.

PMID- 10966249
TI  - Response of erythropoiesis and iron metabolism to recombinant human
      erythropoietin in intensive care unit patients.
AB  - OBJECTIVES: Critically ill patients often are anemic, which may impair oxygen
      delivery. Transfusion of red cells and supplementation with vitamins or iron are
      the usual therapeutic strategies, whereas only sporadic data are available on the
      use of epoetin alfa in these patients. We investigated endogenous erythropoietin
      (EPO) production and the response to epoetin alfa in anemic intensive care unit
      (ICU) patients. DESIGN: Randomized, open trial. SETTING: Multidisciplinary ICU in
      a single secondary care center. PATIENTS: Thirty-six critically ill patients
      admitted to the ICU who became anemic (hemoglobin concentration, <11.2 g/dL or
      <12.1 g/dL in case of cardiac disease) were randomized to one of three study
      groups. INTERVENTIONS: All patients received folic acid (1 mg) daily. The control
      group received no additional therapy, the iron group received 20 mg of iron
      saccharate intravenously (iv) daily for 14 days. The EPO group received iv iron
      and epoetin alfa (300 IU/kg) subcutaneously on days 1, 3, 5, 7, and 9.
      MEASUREMENTS AND MAIN RESULTS: Blood and reticulocyte counts were measured daily
      for 22 days. Serum EPO, C-reactive protein, serum transferrin receptor, and iron
      variables were measured on days 0, 2, 6, 10, and 21. Blood loss and red cell
      transfusions were recorded. Serum EPO concentrations were inappropriately low for
      the degree of anemia at baseline, with no difference between patients with and
      without renal failure. Exogenous administration of EPO increased EPO
      concentrations from 23+/-13 to a maximum of 166+/-98 units/L on day 10 (p < .05).
      Reticulocyte count increased exclusively in the EPO group from 56+/-33 x 10(9)/L
      to a maximum of 189+/-97 on day 13 (p < .05). Serum transferrin receptor rose
      only in the EPO group from 3.7+/-1.4 to 8.6+/-3.1 mg/L on day 10 (p < .05) and
      remained elevated on day 21, indicating an increase in erythropoiesis. Hemoglobin
      concentration and platelet count remained identical in the three study groups.
      CONCLUSION: Endogenous EPO concentrations are low in critically ill patients. The
      bone marrow of these patients is able to respond to exogenous epoetin alfa, as
      shown by elevated concentrations of reticulocytes and serum transferrin
      receptors.

PMID- 10966250
TI  - Nitric oxide indices in human septic shock.
AB  - OBJECTIVES: To study the relation between nitrite, nitrate, nitrotyrosine, and
      nitrosothiols as NO indices in human septic shock. DESIGN: A prospective clinical
      study. SETTING: Intensive care units in a university hospital and a central
      county hospital. PATIENTS: Sixteen patients admitted for septic shock. Nine
      healthy volunteers served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Patients with septic shock had a hyperdynamic circulatory response and
      required infusion of at least two vasopressors to maintain systemic blood
      pressure. Four episodes of recurrent shock occurred in two patients. Heparinized
      plasma was collected once daily for analysis of NO indices. Peak plasma
      concentrations of nitrite + nitrate (NOx) were elevated in first episodes of
      septic shock; 144+/-39 microM vs. controls, 20+/-3 microM (p < .05). Peak plasma
      NOx concentrations in recurrent shocks were; 160+/-19 microM. Peak plasma
      concentrations of 3-nitrotyrosine (NT) were elevated in primary septic shock
      102+/-19 pmol x mL(-1) vs. controls 14+/-6 pmol x mL(-1) (p < .05). Peak NT
      concentrations were 117+/-37 pmol x mL(-1) in recurrent septic shock. Peak plasma
      NT concentrations did not coincide with peak NOx concentrations in half of the
      episodes of septic shock. Plasma NT was elevated (59+/-15 pmol x mL(-1) vs.
      controls 14+/-6 pmol x mL(-1), p < .05) in patients with normal plasma NOx
      concentrations throughout septic shock. Plasma concentrations of nitrosothiols
      did not change during septic shock. CONCLUSIONS: Plasma concentrations of NOx and
      NT are elevated in primary episodes of septic shock and may also be elevated in
      secondary septic shock, but too few episodes of recurrent septic shock occurred
      to allow firm conclusions. Plasma concentrations of NT are elevated in patients
      with septic shock with normal plasma NOx concentrations, indicating that plasma
      concentrations of NOx may not always accurately reflect NO production. Reactive
      nitrogen species may be formed in septic shock, and measuring both NOx and NT may
      give a better indication of NO production in septic shock than NOx alone. Plasma
      levels of nitrosothiols did not change during septic shock.

PMID- 10966251
TI  - Scoring systems in cancer patients admitted for an acute complication in a
      medical intensive care unit.
AB  - OBJECTIVE: To validate and compare two severity scoring systems, the Acute
      Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute
      Physiology Score (SAPS) II and to determine their prognostic value for mortality
      during the hospital stay and after discharge in a specific group of cancer
      patients admitted to intensive care unit (ICU) for an acute medical complication.
      DESIGN: Prospective cohort study. SETTING: The medical ICU of a European cancer
      hospital. SUBJECTS: A total of 261 consecutive cancer patients admitted to ICU
      for an acute medical complication. MEASUREMENTS: Variables included into the
      APACHE II and SAPS II scores, as well as characteristics of the cancer, were
      collected during the first 24 hrs of the ICU stay. Hospital and in-ICU
      mortalities, overall survival, and survival after day 30 were measured. RESULTS:
      Observed hospital and ICU mortalities were 33% and 23%. Median survival time was
      94 days and 1-yr survival rate was 23%. The mean predicted risk of death was
      26.5% with APACHE II and 26.1% with SAPS II. Correlation between both systems was
      excellent. Calibration for mortality prediction ability of both scoring systems
      was similar. Discrimination between survivors and nonsurvivors was superior with
      SAPS II according to the area under the receiver operating characteristic curve
      but was better with APACHE II for survivors using thresholds minimizing the
      overall misclassification rates. Multivariate prognostic analysis showed that the
      scoring systems were the only significant factors for hospital and in-ICU
      mortalities, whereas characteristics related to the cancer (extent, phase) were
      the factors predicting survival after discharge. CONCLUSION: The prognosis of
      cancer patients admitted to ICU for a medical problem is first determined by the
      acute physiologic changes induced by the complication, as evaluated by the
      severity scores. There is no major difference between the two assessed scoring
      systems. They are, however, not accurate enough to be used in the routine
      management of these patients. After recovery from complications, characteristics
      related to the neoplastic disease, however, retrieve their independent influence
      on the further survival.

PMID- 10966252
TI  - Discrimination of sepsis and systemic inflammatory response syndrome by
      determination of circulating plasma concentrations of procalcitonin, protein
      complement 3a, and interleukin-6.
AB  - OBJECTIVE: To evaluate whether plasma concentrations of procalcitonin (PCT),
      interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase),
      and the C-reactive protein (CRP) determined directly after the clinical onset of
      sepsis or systemic inflammatory response syndrome (SIRS) discriminate between
      patients suffering from sepsis or SIRS and predict the outcome of these patients.
      DESIGN: Prospective study. SETTING: Medical intensive care unit at a university
      hospital. PATIENTS: Twenty-two patients with sepsis and 11 patients with SIRS.
      MEASUREMENTS AND MAIN RESULTS: The plasma concentrations of PCT, C3a, and IL-6
      obtained < or =8 hrs after clinical onset of sepsis or SIRS but not those of
      elastase or CRP were significantly higher in septic patients (PCT: median, 16.8
      ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807 ng/mL, range, 422-4788
      ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004 pg/mL, p = .009, all Mann
      Whitney rank sum test) compared with patients suffering from SIRS (PCT: median,
      3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range, 279566 ng/mL; IL
      6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a, and IL-6 to
      discriminate between septic and SIRS patients was determined in a receiver
      operating characteristic analysis. C3a was the best variable to differentiate
      between both populations with a maximal sensitivity of 86% and a specificity of
      80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a
      specificity of 80%) was achieved when PCT and C3a were combined in a "sepsis
      score." C3a concentrations also helped to predict the outcome of patients. Based
      on the sepsis score, a logistic regression model was developed that allows a
      convenient and reliable determination of the probability of an individual patient
      to suffer from sepsis or SIRS. CONCLUSIONS: Our data show that the determination
      of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS
      patients than the variables CRP and elastase, routinely used at the intensive
      care unit. The determination of PCT and C3a plasma concentrations appears to be
      helpful for an early assessment of septic and SIRS patients in intensive care.

PMID- 10966253
TI  - Sampling methods for ventilator-associated pneumonia: validation using different
      histologic and microbiological references.
AB  - OBJECTIVE: To validate sampling techniques (tracheobronchial aspirates, protected
      specimen brush, and bronchoalveolar lavage, both conventional and protected) for
      the detection of ventilator-associated pneumonia (VAP) and causative
      microorganisms according to different histologic and microbiological references.
      DESIGN: Immediate, multiple bilateral lung biopsy, postmortem study. SETTING:
      Respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS:
      Twenty-five mechanically ventilated patients (>72 hrs) who died in our intensive
      care unit. MEASUREMENTS: Lung tissue histologic examination and quantitative
      cultures (16 specimens/patient). The following four references for the diagnostic
      techniques were used: histology of guided lung biopsy, histology of blind lung
      biopsy, combined guided and blind lung biopsy histology and microbiology of lung
      tissue, and microbiology of lung tissue. RESULTS: Sensitivities when histologic
      reference tests were used ranged from 16% to almost 40%, whereas specificity
      rates were always <80%. When we combined both lung histology of guided or blind
      specimens and microbiology of lung tissue, all diagnostic techniques achieved
      considerably higher but still limited diagnostic yields (sensitivity range 43% to
      83%; specificity range 67% to 91%). Causative organisms were missed in a
      significant number of cases by all techniques (17% to 83%). CONCLUSIONS: The
      diagnostic performances of different diagnostic techniques strongly depend on the
      reference used. All techniques for detecting VAP are of limited value. Finding a
      balance between clinical judgment and microbiological results is crucial to
      appropriately manage patients with VAP.

PMID- 10966255
TI  - Noninvasive whole-body electrical bioimpedance cardiac output and invasive
      thermodilution cardiac output in high-risk surgical patients.
AB  - OBJECTIVE: To evaluate the reliability of whole-body impedance cardiography with
      two electrodes on either both wrists or one wrist and one ankle for the
      measurement of cardiac output compared with the thermodilution method. DESIGN:
      Prospective, clinical investigation SETTING: Surgical intensive care unit of a
      university-affiliated community hospital. PATIENTS: Simultaneous cardiac output
      measurements by noninvasive whole-body impedance cardiography (nCO) and invasive
      thermodilution (thCO) in 22 high-risk surgical patients scheduled for extended
      surgery requiring perioperative pulmonary artery catheter monitoring.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 109 sets of
      measurements consisting of 455 single comparison measurements between nCO and
      thCO were included in the analysis. The mean cardiac output difference between
      the two methods was 1.62 L/min with limits of agreement (2 SD) of +/- 4.64 L/min.
      The inter-measurement variance was slightly higher for nCO. The correlation
      coefficient between nCO and thCO was r2 = 0.061 (p < .001) for single
      measurements and r2 = 0.083 (p < .002) for sets of three to six measurements. The
      two most predictive factors for between-method differences were the absolute thCO
      value (r2 = 0.13; p < .001) and whether or not a continuous nitroglycerin
      infusion was used (p < .05, Student's t-test). CONCLUSIONS: Agreement between
      whole-body impedance cardiography and thermodilution in the measurement of
      cardiac output was unsatisfactory. Factors that can explain these differences are
      differences between the populations used for calibration of nCO and the study
      population, the influence of changing peripheral perfusion, and the effect of a
      supranormal hemodynamic state on the bioimpedance signal. Whole-body impedance
      cardiography cannot be recommended for assessing the hemodynamic state of high
      risk surgical patients as studied in this investigation.

PMID- 10966254
TI  - Spectral analysis of systemic arterial pressure and heart rate signals of
      patients with acute respiratory failure induced by severe organophosphate
      poisoning.
AB  - OBJECTIVE: Spectral analysis of systemic arterial pressure (BP) and heart rate
      (HR) signals may be an alternative prognostic tool for predicting patient outcome
      in the intensive care unit (ICU). We evaluated the applicability of the same
      analysis in the emergency department for predicting mortality in patients with
      acute respiratory failure induced by severe organophosphate poisoning. DESIGN:
      Prospective collection of data from 14 emergency service patients. SETTING:
      Emergency service at a large, university-affiliated medical center. PATIENTS:
      Consecutive patients who, after attempting suicide by ingesting organophosphates,
      were admitted to the ICU of the emergency service with acute respiratory failure
      and remained for > or =2 days INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Demographic and survival data and day 1 Acute Physiology and Chronic Health
      Evaluation (APACHE) II and Glasgow Coma Scale scores were recorded. Continuous,
      on-line, real-time spectral analysis of BP and HR signals was carried out during
      the first 12 hrs after admission. We then computed the total sum of power density
      during this period of the low-frequency (0.04-0.15 Hz) and very low-frequency
      (0.004-0.04 Hz) components in the BP and HR spectra, along with the averaged
      values of mean BP and HR. Eight patients who recovered exhibited vigorous power
      in the low-frequency and very low-frequency components of their BP and HR
      signals. There was a significant reduction in the power density of those four
      spectral components in three patients who eventually died. Three patients
      discharged in a vegetative state manifested significantly reduced power in the
      low-frequency component in their BP spectra, with maintained power in the other
      three spectral components. APACHE II and Glasgow Coma Scale scores of the
      recovered patients were discernibly different from those of patients who
      eventually died or who became vegetative. None of the 14 patients showed
      appreciable differences in mean BP, mean HR, erythrocyte or plasma cholinesterase
      concentration, or atropine requirement during the first 24 hrs. CONCLUSION: The
      low-frequency and very low-frequency components of BP and HR signals may be a
      sensitive alternative index for early prediction of mortality in patients with
      acute respiratory failure induced by severe organophosphate poisoning.

PMID- 10966256
TI  - Performance of the Mortality Probability Models in assessing severity of illness
      during the first week in the intensive care unit.
AB  - OBJECTIVE: To extend the Mortality Probability Models (MPM) II severity system to
      time periods between 4 and 7 days after admission to the intensive care unit
      (ICU). DESIGN: Prospective inception cohort. SETTING: Fifteen adult medical and
      surgical ICUs in Spain. PATIENTS: A total of 1,441 patients aged > or =18 yrs
      consecutively admitted from April 1, 1995 through July 31, 1995. INTERVENTIONS:
      Prospective data collection during the stay of the patient in the ICU. Data
      collected included demographic information, length-of-stay and vital status at
      both ICU and hospital discharge, as well as all variables necessary for computing
      the MPM II system at admission and during the first 7 days of stay in the ICU
      MEASUREMENTS AND MAIN RESULTS: Calibration and discrimination of the four
      existing MPM II models (MPM0, MPM24, MPM48, and MPM72) were assessed in the study
      database. The MPM II system overestimated the mortality of patients with
      probabilities of death > or =0.4. The MPM24 model was customized. Models for time
      periods between 48 hrs and 7 days (MPM48 to MPMd7) were obtained using the same
      strategy that was used to develop the original MPM48 and the MPM72 models. The
      variable coefficients of the MPM24 model were kept fixed and the constant terms
      of the MPM48 to MPMd7 models were estimated by logistic regression. The constant
      term stabilized after the fourth day of admission and it was similar to the
      constant term of the MPM72 model. The customized MPM72 performed very well for
      days 4 to 7 after admission to the ICU. CONCLUSIONS: If the patient's condition
      stays the same day after day, the probability of dying in the hospital increases
      until 72 hrs, and then stabilizes. A severity measure that performs well at 72
      hrs can be a useful tool for measuring severity at later time periods.

PMID- 10966257
TI  - Correlation between endotoxin level and bacterial count in bronchoalveolar lavage
      fluid of ventilated patients.
AB  - OBJECTIVE: To assess the predictive value of the endotoxin level in the
      bronchoalveolar lavage (BAL) and to propose to the clinician a guide in the
      diagnosis of gram-negative bacterial (GNB) pneumonia. DESIGN: Retrospective and
      prospective studies to investigate the relation between endotoxin level and
      quantitative bacterial culture of BAL and to test the predictive value of a
      defined threshold. SETTING: University hospital general intensive care unit.
      PATIENTS: In the first part of the study, 77 consecutive ventilated patients with
      clinical suspicion of nosocomial pneumonia between January 1995 and January 1996.
      In the second part of the study, 93 consecutive ventilated patients studied
      prospectively between February 1996 and April 1997. MEASUREMENTS AND MAIN
      RESULTS: Quantitative cultures for aerobic bacteria were performed directly from
      the fluid. Bacterial species were determined with standard techniques. The
      detection of endotoxin in BAL was made using a quantitative chromogenic Limulus
      assay. In the retrospective analysis, a significant correlation between
      quantitative GNB cultures and BAL endotoxin levels was observed (r2 = 0.60, p <
      .0001). An endotoxin level > or = 4 endotoxin units/mL (EU/mL) distinguishes
      patients with a significant GNB count from colonized patients with a sensitivity
      of 92.6%, a specificity of 81.4% and a correct classification rate of 84.9%. In
      the prospective analysis, the 4 EU/mL threshold permits identification of
      infected patients with a sensitivity of 82.2%, a specificity of 95.6%, and a
      correct classification rate of 90.3%. The receiver operating characteristic curve
      analysis showed that the Limulus assay still had a good discrimination power in
      the prediction of significant bacterial count in BAL fluid. CONCLUSIONS:
      Endotoxin detection immediately after bronchoscopy is a distinct advantage to the
      clinician because antimicrobial gram-negative therapy may be immediately
      justified according to the results.

PMID- 10966258
TI  - Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to
      the ischemic periphery.
AB  - OBJECTIVE: Hyperbaric oxygen (HBO) increases oxygen supply to anoxic areas. To
      examine the therapeutic effect of HBO on ischemic stroke, we measured infarct
      volume as well as cerebral blood flow (CBF), oxygen supply, and lipid
      peroxidation in the ischemic periphery. DESIGN: Prospective experimental study in
      rats. SETTING: Experimental laboratory in a university teaching hospital.
      SUBJECTS: Thirty-eight adult rats. INTERVENTION: The rats were anesthetized (1%
      halothane) and intubated. Focal ischemia was induced by ligating the right middle
      cerebral and right common carotid arteries. Nineteen animals were exposed to 2
      hrs of HBO (100% oxygen, 3 atmospheres absolute), initiated 10 mins after the
      onset of ischemia. The remaining animals were kept at ambient pressure and used
      as controls. MEASUREMENTS AND MAIN RESULTS: At the initiation of ischemia, CBF
      measured by a laser-Doppler flow probe placed in the ischemic periphery was
      reduced to 47%+/-11% and 51%+/-15% of normal levels in animals exposed or not to
      HBO, respectively. These altered values were not affected further by
      administration of HBO and remained stable throughout a 2-hr observation period.
      Arterial oxygen pressure and content were significantly increased to 1571+/-130
      torr (209.41+/-17.32 kPa; p < .0001) and 1.03+/-0.04 mmol/dL (p < 0.0001),
      respectively, in HBO-treated animals compared with nontreated animals (139+/-14
      torr [18.53+/-1.87 kPa] and 0.86+/-0.04 mmol/dL, respectively). The calculated
      increase in the oxygen supply to the ischemic periphery was 20%. The infarct
      volume of HBO-treated animals measured 24 hrs after the onset of focal cerebral
      ischemia was significantly reduced by 18% (HBO-treated, 132+/-13 mm3 vs.
      nontreated, 161+/-29 mm3; p = .02). Lipid peroxidation was unchanged after 120
      mins of HBO administration in the cerebral cortex where the laser-Doppler flow
      probe was placed. CONCLUSIONS: HBO at 3 atmospheres absolute reduced infarct
      volume by increasing oxygen supply to the ischemic periphery without aggravating
      lipid peroxidation, suggesting that HBO can be useful in treating stroke victims.

PMID- 10966259
TI  - Alterations in tissue oxygen consumption and extraction after trauma and
      hemorrhagic shock.
AB  - OBJECTIVES: Although trauma and hemorrhage are associated with tissue
      hypoperfusion and hypoxemia, changes in oxygen delivery (DO2), oxygen consumption
      VO2), and oxygen extraction at the organ level in a small animal (such as the
      rat) model of trauma and hemorrhage have not been examined. Therefore, the
      objectives of this study were to determine whether blood flow, DO2, VO2, and
      oxygen extraction ratio in various organs are differentially altered after trauma
      hemorrhagic shock and acute resuscitation in the rat. DESIGN: Prospective,
      randomized animal study. SETTING: A university research laboratory. SUBJECTS:
      Male Sprague-Dawley rats (n = 6-7 animals/group) weighing 275-325 g.
      INTERVENTIONS: Male rats underwent laparotomy (i.e., soft tissue trauma) and were
      bled to and maintained at a blood pressure of 40 mm Hg until 40% of shed blood
      volume was returned in the form of lactated Ringer's solution. They were then
      resuscitated with four times the volume of shed blood with lactated Ringer's
      solution for 60 mins. At 1.5 hrs postresuscitation, cardiac output and blood flow
      were determined by using strontium-85 microspheres. Blood samples (0.15 mL each)
      were collected from the femoral artery and vein and the hepatic, portal, and
      renal veins to determine total hemoglobin and oxygen content. Systemic and
      regional DO2, VO2, and oxygen extraction ratio were then calculated. MEASUREMENTS
      AND MAIN RESULTS: Both the systemic hemoglobin and systemic arterial oxygen
      content in hemorrhaged animals at 1.5 hrs postresuscitation were >50% lower as
      compared with sham-operated controls. Cardiac output and blood flow in the liver,
      small intestine, and kidneys decreased significantly, but blood flow in the brain
      and heart remained unaltered after hemorrhage and resuscitation. Systemic DO2 and
      VO2 were 73% and 54% lower, respectively, than controls at 1.5 hrs after
      resuscitation. Similarly, regional DO2 and VO2 in the liver, small intestine, and
      kidneys decreased significantly under such conditions. In addition, the liver had
      the most severe reduction in VO2 (76%) among the tested organs. However, the
      oxygen extraction ratio in the liver of sham animals was the highest (72%) and
      remained unchanged after hemorrhage and resuscitation. CONCLUSION: Because the
      liver experienced the most severe reduction in VO2 associated with an unchanged
      oxygen extraction capacity, this organ appears to be more vulnerable to hypoxic
      insult after hemorrhagic shock.

PMID- 10966260
TI  - Hypertonic saline-dextran improves intestinal perfusion and survival in porcine
      endotoxin shock.
AB  - OBJECTIVE: To examine the effects of hypertonic (7.5%) saline-6% dextran 70 (HSD)
      and isotonic (0.9%) saline-6% dextran 70 (ISD) on cardiovascular function and
      intestinal perfusion in experimental endotoxin shock. DESIGN: Experimental,
      randomized, unblinded, interventional study. SETTING: University experimental
      animal laboratory. SUBJECTS: Anesthetized and mechanically ventilated landrace
      pigs (n = 24). INTERVENTIONS: Induction of endotoxin (ET) shock by infusion of
      Escherichia coil lipopolysaccharide endotoxin (serotype 0111: B4) followed by no
      fluid treatment (control; C) or small-volume (4 mL/kg) treatment with HSD or ISD.
      MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, central venous pressure,
      pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac output,
      portal vein blood flow, intestinal microcirculation, intramucosal (regional)
      P(CO2), intestinal-arterial gap of CO2, and intramucosal pH were monitored, and
      blood gases were analyzed. Infusion of ET resulted in hypokinetic shock, which in
      untreated animals led to cardiovascular deterioration and a survival rate of only
      33% at 300 mins after start of ET infusion. ISD treatment transiently improved
      hemodynamic variables and mucosal blood flow but did not affect the survival rate
      vs. C. Significant beneficial, long-lasting effects of HSD infusion on
      hemodynamics, especially on mucosal blood flow and intramucosal pH, were
      demonstrable, resulting in a survival rate of 86%. The relative risk of death at
      300 mins was 1.20 for ISD vs. C and 0.17 for HSD vs. C. CONCLUSION: Small-volume
      HSD resuscitation is much more effective than ISD resuscitation. Variables that
      were improved include cardiac output, portal blood flow, and intestinal mucosal
      blood flow in ET shock, all of which improve survival. Such beneficial effects of
      HSD on splanchnic perfusion may be of value in treating critically ill septic
      patients in the intensive care unit.

PMID- 10966261
TI  - Impact of endothelin-1 in endotoxin-induced pulmonary vascular reactions.
AB  - OBJECTIVES: Elevated endothelin-1 (ET-1) levels have been detected during sepsis.
      The aim of the study was to examine the role of thromboxane A2 (TXA2) and ET-1 in
      pulmonary vascular reactions after endotoxin (LPS) challenge. DESIGN: Prospective
      experimental study in rabbits. SETTING: Experimental laboratory in a university
      teaching hospital. SUBJECTS: Twenty-four adult rabbits of either sex.
      INTERVENTIONS: Experiments were performed on 30 isolated and ventilated rabbit
      lungs, which were perfused with a saline solution containing 10% autologous
      blood. MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial pressure and lung weight
      gain were continuously registered. Perfusate samples were drawn intermittently to
      determine ET-1, TXA2, and prostacyclin (PGI2) concentrations. LPS isolated from
      Escherichia coli (0.5 mg/mL; n = 6) was added to the perfusate. A marked
      pulmonary arterial pressure increase followed by massive edema formation after 60
      mins was observed after LPS injection. At the same time, elevated TXA2 and PGI2
      levels in the perfusate were measured. ET-1 was detected 30 mins after LPS
      infusion (13.4+/-2.6 fmol/L). Pretreatment with the ET(A) receptor antagonist
      LU135252 (10(-6) M; n = 6) almost completely suppressed the pressure reaction
      after endotoxin injection (p < .01 at 50 and 60 mins) and reduced edema formation
      (p < .05). The cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6) was as
      effective as LU135252 in preventing vascular reactions after LPS injection.
      CONCLUSIONS: Pretreatment with the ET(A) receptor antagonist LU135252 and the
      cyclooxygenase inhibitor diclofenac reduced pulmonary vascular reactions after
      LPS challenge. Based on the current data, we conclude that the pulmonary arterial
      pressure increase and edema formation after LPS injection are related to an ET-1-
      and TXA2-dependent mechanism.

PMID- 10966262
TI  - Inhibition of neutrophil activation by ranitidine contributes to prevent stress
      induced gastric mucosal injury in rats.
AB  - OBJECTIVE: Activated neutrophils play a critical role in stress-induced gastric
      mucosal injury. We investigated the effect of ranitidine, an H2-receptor
      antagonist, on neutrophil activation in vitro and in rats with stress-induced
      gastric mucosal injury. DESIGN: Prospective, randomized, blinded, controlled
      study. SETTING: Research laboratory at a university medical center.
      INTERVENTIONS: Effects of ranitidine on neutrophil elastase release, production
      of O2-, intracellular calcium concentration and expression of adhesion molecules
      CD11b and CD18 were examined in human neutrophils in vitro. The effect of
      ranitidine (30 mg/kg iv) on the development of gastric mucosal injury, neutrophil
      accumulation, and lipid peroxidation was investigated in male Wistar rats
      subjected to water-immersion restraint stress. MEASUREMENTS AND MAIN RESULTS:
      Ranitidine inhibited the release of neutrophil elastase as well as the production
      of O2-, the increase in the concentrations of intracellular calcium, a second
      messenger of neutrophil activation, and increases in CD11b and CD18 expression,
      in activated neutrophils. Ranitidine did not affect the expression of E-selectin
      on endothelial cells in vitro. Ranitidine significantly inhibited gastric
      accumulation of neutrophils and gastric mucosal lipid peroxidation in rats
      subjected to stress. Although oral administration of acid reversed the preventive
      effect of pirenzepine, an anti-cholinergic drug that inhibits gastric acid
      secretion, it did not affect the preventive effect of ranitidine. Leukocytopenia
      produced effects similar to those of ranitidine in animals subjected to stress.
      CONCLUSIONS: Inhibition of neutrophil activation and gastric acid secretion by
      ranitidine might contribute to reduce stress-induced gastric mucosal injury.

PMID- 10966263
TI  - Treatment with an endothelin type A receptor-antagonist after cardiac arrest and
      resuscitation improves cerebral hemodynamic and functional recovery in rats.
AB  - OBJECTIVE: Successful resuscitation of the brain after cardiac arrest requires
      unimpaired microcirculatory reperfusion. Postischemic cerebral hypoperfusion
      presumably is mediated through activation of endothelin type A receptors (ET(A)).
      The effect of the selective ET(A) antagonist BQ123 on cerebral blood flow and
      function was studied in a rat model of cardiac arrest. DESIGN: Prospective,
      randomized trial. SETTING: Experimental animal laboratory. SUBJECTS: Twelve male
      Sprague-Dawley rats (290-350 g). INTERVENTIONS: Cardiac arrest for 12 mins was
      induced by electrical fibrillation of the heart, followed by standardized
      cardiopulmonary resuscitation. BQ123 (0.8 mg/kg; n = 6) or its vehicle (saline; n
      = 6) was injected intravenously at 15 mins after the return of spontaneous
      circulation. MEASUREMENTS: Cortical blood flow was measured by laser-Doppler
      flowmetry, electrophysiological function by recording the amplitude of
      somatosensory evoked potentials, vascular reactivity by ventilation with 6% CO2,
      and the functional coupling of blood flow by recording the laser-Doppler flow
      (LDF) changes during somatosensory stimulation. Hemodynamic and functional
      cerebral recovery was monitored for 3 hrs after the return of spontaneous
      circulation. MAIN RESULTS: Forty-five minutes after the return of spontaneous
      circulation, postischemic hypoperfusion developed in both groups, as reflected by
      a decrease of the LDF signal to about 60% of the preischemic level. In untreated
      animals, hypoperfusion persisted throughout the observation time, but in animals
      receiving BQ123, LDF gradually returned to normal. CO2 reactivity in untreated
      animals was severely reduced for 2-3 hrs after the onset of recirculation,
      whereas after BQ123 treatment it returned to normal and after 2 hrs even above
      normal. The ET(A) antagonist also induced a more rapid recovery of the
      somatosensory evoked potentials amplitude and of the functional blood flow
      response to somatosensory stimulation, but these parameters did not recover
      completely within the observation period. CONCLUSIONS: Application of the ET(A)
      antagonist BQ123 during the early reperfusion period after cardiac arrest
      shortens postischemic cerebral hypoperfusion and accelerates the restoration of
      the cerebrovascular CO2 reactivity and the recovery of electrophysiologic
      function.

PMID- 10966264
TI  - Endothelin type A-antagonist improves long-term neurological recovery after
      cardiac arrest in rats.
AB  - OBJECTIVE: Antagonists of endothelin (ET(A)) receptors improve postischemic
      hypoperfusion. In this study we investigated whether the selective ET(A)
      antagonist BQ123 also improves postischemic functional recovery. STUDY DESIGN:
      Cardiac arrest of 12 mins duration was induced in rats by electrical fibrillation
      of the heart, followed by advanced cardiopulmonary resuscitation. BQ123 (0.8
      mg/kg; n = 9) or its vehicle (saline; n = 9) was injected intravenously at 15
      mins after the return of spontaneous circulation. The neurologic deficit was
      scored daily for 7 days after resuscitation by rating consciousness, various
      sensory and motor functions, and coordination tests. On day 7, we measured
      functional coupling of cerebral blood flow under halothane anesthesia by
      recording laser-Doppler flow during electrical forepaw stimulation, and we
      measured vascular reactivity to CO2 by measuring the laser-Doppler flow change
      during ventilation with 6% CO2. The brains were perfusion-fixated with 4%
      paraformaldehyde, and the histopathologic damage was evaluated in the CA1 sector
      of hippocampus, in the motor cortex, and in the cerebellum. RESULTS: Treatment
      with BQ123 had no effect on histopathologic damage, but it significantly improved
      neurologic recovery. In all nine treated rats, neurologic performance returned to
      near normal within 2 days whereas four of nine untreated animals developed
      spastic paralysis of the hind limbs and severe coordination deficits. BQ123 also
      normalized CO2 reactivity and improved the functional cerebral blood flow
      response to somatosensory stimulation. CONCLUSIONS: The ET(A)-antagonist BQ123
      significantly improves neurologic outcome after 12 mins of cardiac arrest. The
      apparent restoration of vascular reactivity demonstrates a correlation between
      hemodynamic factors and functional recovery.

PMID- 10966265
TI  - Influence of heparin and hirudin on endothelial binding of antithrombin in
      experimental thrombinemia.
AB  - OBJECTIVE: During the last decade, experimental and clinical evidence has
      accumulated that antithrombin (AT) exerts anti-inflammatory effects when given in
      high doses. Meanwhile, AT substitution has been shown to significantly increase
      prostacyclin release. However, the link between endothelial AT binding and anti
      inflammatory AT effects remains to be established in vivo, although heparin has
      been shown to counteract anti-inflammatory AT effects. We hypothesized that the
      administration of heparin in endotoxin-challenged rats would decrease endothelial
      AT binding and systemic prostacyclin concentrations. DESIGN: Prospective,
      randomized, controlled experimental in vivo study. SETTING: Research laboratory
      of a university hospital. ANIMALS: Fifty-six Wistar rats. INTERVENTIONS: Baseline
      values of coagulation variables were measured in six animals. Forty of 50 Wistar
      rats in the study groups were given endotoxin (50 mg x kg(-1) iv) and were
      treated with saline (group LPS), AT (15 units x kg(-1) x hr(-1)) (LPS+AT), AT and
      heparin (80 IU x kg(-1) x hr(-1)), or AT and hirudin (0.12 mg x kg(-1) x hr(-1));
      the other 10 received saline instead of endotoxin and were treated with AT alone.
      Before endotoxin application, a tracheostomy was performed, and venous and
      arterial catheters were inserted for blood sampling and infusion. MEASUREMENTS:
      Intravital endothelial AT binding was studied by using fluorescence
      isothiocyanate-marked antibodies during intravital microscopy of intestinal
      submucosal venules. Systemic prostacyclin, thrombin-AT complex, and fibrinogen
      concentrations were measured after 4 hrs. Intergroup differences were tested by
      Kruskal-Wallis analysis of variance on ranks. MAIN RESULTS: AT and AT + heparin
      were equally effective in inhibiting systemic procoagulant turnover as reflected
      by fibrinogen concentrations. Only the administration of AT + hirudin
      significantly prevented fibrinogen consumption (p < .05). In contrast with all
      other treatments, the administration of heparin significantly reduced intravital
      endothelial AT binding (p < .05). However, prostacyclin concentrations were
      similarly increased in all endotoxin-challenged study groups irrespective of the
      anticoagulatory treatment. CONCLUSIONS: There is evidence that heparin in
      contrast with hirudin prevents AT from being bound to the endothelial cell
      surface in this experimental model. Under low-dose AT substitution, systemic
      prostacyclin concentrations do not depend on whether heparin or hirudin is used
      for thrombin inhibition. These results support the view that heparin may
      counteract anti-inflammatory AT effects by keeping AT away from its endothelial
      binding sites; however, the results question the view that decreased endothelial
      prostacyclin release is solely responsible.

PMID- 10966266
TI  - Surfactant treatment impairs gas exchange in a canine model of acute lung injury.
AB  - The effectiveness of surfactant (SURF) treatment in acute lung injury in the
      adult is controversial. In this study, we tested the effectiveness of early
      surfactant treatment in a commonly used animal model of acute lung injury,
      phorbol-myristate acetate (PMA), to see if it would attenuate the progression of
      lung injury. We measured the effect on lung compliance and whether positive end
      expiratory pressure (PEEP) (10 cm H2O) during SURF administration had a
      synergistic effect. METHODS: Four groups of anesthetized dogs were studied: a)
      normals; b) PMA injury only; c) PMA injury + SURF; and d) PMA + SURF + PEEP. Lung
      injury was induced with 25-30 microg/kg of PMA. Responses were measured over 7
      hrs. Surfactant was administered in the form of Survanta, 4 x 25 mg/kg doses via
      tracheal instillation 2.5 hrs after PMA. For the group receiving PEEP, 10 cm H2O
      PEEP was begun 1.5 hrs after PMA, 1 hr before SURF. Postmortem, the left lung was
      excised and inflated three times to total lung capacity (volume at 30 cm H2O) and
      expiratory compliance was measured with 25-100 mL volume increments. The trachea
      was then clamped and trapped volume was determined by water displacement.
      RESULTS: PMA-induced lung injury significantly reduced expiratory compliance and
      total lung capacity (p < .05 from normal). Wet/dry lung weights did not differ
      between groups. SURF without PEEP further decreased lung compliance as compared
      with PMA only. CONCLUSIONS: SURF administration after PMA injury causes marked
      reductions in lung compliance when no PEEP is coadministered. However, the loss
      of static expiratory lung compliance appears partly ameliorated by application of
      PEEP + SURF. Given that tracheal instillation of SURF is known to acutely elevate
      lung impedance in the first few hours after administration, coadministration of
      PEEP appears to be critically important in counteracting these early effects of
      surfactant instillation on the lung.

PMID- 10966267
TI  - Low potential of dobutamine and dopexamine to block intestinal peristalsis as
      compared with other catecholamines.
AB  - OBJECTIVE: Catecholamines are frequently used in critically ill patients to
      restore stable hemodynamics and to improve organ perfusion. One effect of short
      term or long-term administration of catecholamines may be inhibition of
      propulsive motility in the intestine. We therefore analyzed the effect of
      dopexamine, dobutamine, and dopamine on ileal peristalsis and compared their
      action with that of epinephrine and norepinephrine, which have long been known to
      suppress intestinal peristalsis. DESIGN: In vitro study on excised guinea pig
      ileum segments. SETTING: Laboratory for experimental studies at the University.
      SUBJECTS: Isolated guinea pig ileum. INTERVENTIONS: Segments of ileum excised
      from guinea pigs were mounted in a tissue bath in Krebs-Henseleit solution and
      bubbled with 95% oxygen/5% CO2. Luminal perfusion with the same solution was
      performed at a rate of 0.35 mL/min. The bath temperature was kept at 36.5 degrees
      C. Peristalsis was recorded via changes in the intraluminal pressure. The drugs
      under investigation (dopamine, epinephrine, norepinephrine, dobutamine, and
      dopexamine) were added to the tissue bath. MEASUREMENTS AND MAIN RESULTS: Low
      concentrations of each catecholamine, except epinephrine, caused a decrease in
      the pressure threshold, which reflects a stimulatory effect on peristalsis.
      Higher catecholamine concentrations caused a concentration-related increase in
      the threshold, cumulating in a complete block of peristalsis. The rank order of
      inhibitory potency was epinephrine > norepinephrine > dopamine > dobutamine
      approximately dopexamine. Dobutamine and dopexamine were about 500-fold less
      active than epinephrine in suppressing peristalsis. CONCLUSIONS: This study shows
      that dobutamine and dopexamine have the least potential to block propulsive
      motility in the intestine, whereas epinephrine demonstrates the most adverse
      inhibitory effect. Because at low concentrations dobutamine and dopexamine even
      stimulate peristalsis, these drugs appear to be superior compared with other
      catecholamines with regard to their direct effects on intestinal motility.

PMID- 10966268
TI  - Nitric oxide synthase inhibition increases venular leukocyte rolling and adhesion
      in septic rats.
AB  - OBJECTIVE: Excess production of nitric oxide (NO) has been implicated in
      hypotension and blood flow abnormalities in sepsis, but NO is also an important
      inhibitor of leukocyte rolling and adhesion. Leukocyte adhesion is increased in
      sepsis despite elevated NO production. We hypothesized that inhibition of NO
      synthase (NOS) could increase leukocyte adhesion in sepsis. DESIGN: Prospective
      animal study. SETTING: Experimental animal laboratory. SUBJECTS: Twenty-five male
      rats, anesthetized with ketamine and acepromazine. INTERVENTIONS: Topical
      superfusion of the nonselective NOS inhibitor N(G)-monomethyl-L-arginine (NMA) on
      skeletal muscle postcapillary venules. MEASUREMENTS AND MAIN RESULTS: Rats made
      septic by cecal ligation and puncture were compared with controls that underwent
      sham ligation. Leukocyte rolling and adhesion were measured in cremasteric
      postcapillary venules of septic and control rats using in vivo videomicroscopy.
      The effects of NOS inhibition on leukocyte rolling and adhesion were also
      measured. After a stable baseline was reached, 1 microM of the nonselective NOS
      inhibitor NMA was suffused topically followed by physiologic buffer. The effects
      of L-arginine on leukocyte rolling and adhesion were also measured, both before
      and after suffusion of NMA. Leukocyte rolling and adhesion was increased in
      septic rats as compared with controls (control 5.5+/-0.9 rolling cells/min, 1.0+/
      0.3 adherent cells/min; septic 13.7+/-2.0 rolling cells/min, 3.1+/-0.6 adherent
      cells/min; p < .001), and NOS inhibition further increased leukocyte rolling and
      adhesion in both septic and control rats (control 14.0+/-1.7 rolling cells/min,
      2.8+/-0.5 adherent cells/min; septic 25+/-2.1 rolling cells/min, 5.4+/-0.5
      adherent cells/min; both p < .001 vs. baseline). Prior suffusion of excess L
      arginine prevented the increase in leukocyte adhesion with NMA in septic rats
      (2.6+/-0.4 adherent cells/min vs. 3.0+/-0.6 adherent cells/min; n = 3; p > .05).
      When administered after NMA, excess L-arginine partially reversed leukocyte
      adhesion in septic rats (5.4+/-0.7 adherent cells/min, with NMA vs. 4.3+/-0.7
      adherent cells/min, after L-arginine; n = 5; p < .05). Venular shear did not
      differ between septic and control rats (600+/-109 (sec(-1)) vs. 620+/-37 (sec(
      1)); p > .05). CONCLUSIONS: Although NOS inhibition may ameliorate hypotension in
      sepsis, such therapy may be deleterious by increasing leukocyte adhesion.

PMID- 10966269
TI  - Relationship between airway pressure and the distribution of gas-liquid interface
      during partial liquid ventilation in the oleic acid lung injury model: fluorine
      19 magnetic resonance imaging study.
AB  - OBJECTIVE: To elucidate the relationship between airway pressure (Paw) and the
      distribution of gas-liquid interface d ring partial liquid ventilation (PLV).
      DESIGN: Prospective, controlled study. SETTING: A research laboratory at a
      university medical center. SUBJECTS: Ten Japanese white rabbits. INTERVENTIONS:
      Ten rabbits were tracheostomized and mechanically ventilated (F(IO2) = 1.0, tidal
      volume = 40 mL, respiratory rate = 25 breaths/min) under general anesthesia. In
      the oleic acid lung injury group (n = 5), oleic acid (0.10-0.12 mL/kg) was
      intravenously administered to make a lung injury model. When PaO2 became <100
      torr (13.3 kPa), 15 mL/kg of perflubron was instilled into the endotracheal tube,
      and PLV was performed for 60 mins. In the control group, PLV was performed for 60
      mins without any insult to the lung. After animals were killed under deep
      anesthesia, Paw was set at 0, 5, 10, 15, 20, 25, 30 cm H2O and fluorine-19
      magnetic resonance imaging was performed. Pressure-volume relationship was
      investigated using proton magnetic resonance imaging. MEASUREMENTS AND MAIN
      RESULTS: Gas-liquid interface reduces fluorine-19 magnetic resonance signal. The
      total lung fluorine-19 signal intensity was reduced by the Paw above the lower
      inflection point on the pressure-volume curve, and severe lung injury interfered
      with establishing gas-liquid interface, especially in the dependent region, even
      during PLV. CONCLUSION: Paw above the lower inflection point on the pressure
      volume curve established gas-liquid interface dose dependently during PLV, and
      severe lung injury with low compliance could cause difficulty in the
      establishment of gas-perflubron interface, especially in the dependent lung
      region.

PMID- 10966270
TI  - Hypocalcemia during porcine endotoxemic shock: effects of calcium administration.
AB  - OBJECTIVE: To evaluate the pathophysiology involved in hypocalcemia in septic
      shock and to investigate the value of calcium administration. DESIGN:
      Prospective, randomized placebo-controlled trial with parallel groups. SETTING:
      Animal research laboratory at the University Hospital of Uppsala. SUBJECTS:
      Twenty-four pigs aged 12-14 wks receiving general anesthesia. INTERVENTIONS:
      Twenty pigs received endotoxin infusion (10 microg/kg/hr) for 6 hrs. Ten of these
      pigs also received a calcium infusion (20 mmol total) in parallel. Four control
      pigs received only saline. MEASUREMENTS AND MAIN RESULTS: At the end of the
      study, blood ionized calcium (Ca2+) had declined from 1.32+/-0.04 mmol/L (mean +/
      SD) to 1.09+/-0.06 mmol/L in pigs receiving endotoxin (p < .05 vs. controls)
      compared with 1.38+/-0.04 mmol/L to 1.25+/-0.07 mmol/L in controls and 1.39+/
      0.03 mmol/L to 1.24+/-0.07 mmol/L in endotoxemic pigs receiving calcium. In both
      endotoxemic groups, total calcium levels in ascites were increased by 56% (p <
      .005 vs. controls), and an accumulation of calcium in the liver was mainly seen
      in the endotoxemic group receiving calcium (p < .008 vs. controls). Total Ca2+
      levels in adiposal tissue and skeletal muscle were similar in all groups. Calcium
      administration did not significantly alter systemic hemodynamics or survival in
      this model of septic shock (four survivors in the endotoxemic group and five in
      the calcium administration group). CONCLUSIONS: Endotoxemia in the pig rapidly
      induced hypocalcemia. Calcium accumulation was found in ascites and in the liver,
      but not in other examined tissues. Calcium administration, restoring the Ca2+
      concentration, did not improve hemodynamics or survival in this model of
      hypodynamic sepsis. Porcine endotoxemic shock, which replicates human septic
      shock, seems to be suitable for evaluating calcium turnover.

PMID- 10966271
TI  - Intraosseous blood gases during hypothermia: correlation with arterial, mixed
      venous, and sagittal sinus blood.
AB  - OBJECTIVE: Especially in pediatric patients with severe hypothermia, intraosseous
      access may be more readily available than intravascular access during an early
      phase of treatment and therefore, may be helpful to optimize management. The
      purpose of this study was to determine whether intraosseous blood gases are
      comparable with arterial, mixed venous, and sagittal sinus blood gases during
      different degrees of hypothermia. DESIGN: Prospective, descriptive laboratory
      investigation using a porcine model. SETTING: University hospital laboratory.
      SUBJECTS: Twelve anesthetized, 12- to 16-wk-old domestic pigs weighing 30-35 kg.
      INTERVENTIONS: Volume-controlled ventilated animals were instrumented with
      arterial, pulmonary artery, sagittal sinus, and 16-gauge intraosseous catheters.
      Blood samples were obtained from each site every 15 mins during surface cooling
      with crushed ice until mean +/- SEM core temperature decreased from 38.5+/-0.1
      degrees C [101.3+/-0.2 degrees F] to 27+/-0.5 degrees C [80.5+/-0.9 degrees F]
      over 2 hrs. MEASUREMENTS AND MAIN RESULTS: Intraindividual correlation of Pco2
      and pH values were determined as the difference (delta) between intraosseous and
      reference blood samples. With hypothermia, absolute values of Pco2 decreased and
      pH increased in samples from all sites. At 27 degrees C, intraosseous--arterial
      delta P(CO2) and delta pH (mean +/- 95% confidence intervals) were 2.6+/-10.6
      torr [0.35+/-1.4 kPa] and -0.11+/-0.07 units; intraosseous - mixed venous were
      0.4+/-12.2 torr [0.05+/-1.6 kPa] and -0.06+/-0.08 units; and intraosseous -
      sagittal sinus were -7.3+/-16 torr [-0.97+/-2.1 kPa] and 0.001+/-0.14 units,
      respectively. Intraosseous Pco2 was not comparable to end-tidal values
      (deltaP(CO2) 17.4+/-14.6 torr [2.3+/-1.9 kPa]), and intraosseous lactate did not
      correlate with arterial, mixed venous, or sagittal sinus values. CONCLUSIONS:
      During hypothermia, intraosseous P(CO2) values were predictable for mixed venous
      Pco2 and arterial P(CO2). Intraosseous pH values also correlated with mixed
      venous and sagittal sinus blood samples. Accordingly, interpretation of blood gas
      values obtained from bone marrow aspirates may be helpful to adjust ventilation
      and optimize fluid and drug therapy during the early treatment of patients with
      severe hypothermia.

PMID- 10966272
TI  - Mechanical ventilation with high positive end-expiratory pressure and small
      driving pressure amplitude is as effective as high-frequency oscillatory
      ventilation to preserve the function of exogenous surfactant in lung-lavaged
      rats.
AB  - OBJECTIVE: To demonstrate that under well-defined conditions, pressure-controlled
      ventilators (PCV) allow settings that are as good as high-frequency oscillatory
      ventilators (HFOV) at preserving the function of exogenous surfactant in lung
      lavaged rats. DESIGN: Experimental, comparative study. SETTING: Research
      laboratory of a large university. SUBJECTS: Sixteen adult male Sprague-Dawley
      rats (280-310 g). INTERVENTIONS: Lung injury was induced by repeated lavage.
      After last lavage, all animals received exogenous surfactant and were then
      randomly assigned to two groups (n = 8 per group). The first group received PCV
      with small pressure amplitudes and high positive end-expiratory pressure. The
      second group received HFOV. In both groups, an opening maneuver was performed by
      increasing airway pressure to improve PaO2/F(IO2) to > or =500 torr. MEASUREMENTS
      AND MAIN RESULTS: Blood gases were measured every 30 mins for 3 hrs. Airway
      pressures were measured with a tip catheter pressure transducer. At the end of
      the study period, a pressure-volume curve was recorded and a broncho-alveolar
      lavage was performed to determine protein content and surfactant composition. The
      results showed that arterial oxygenation in both groups could be kept >500 torr
      during the 3-hr study period by using a mean airway pressure of 13+/-3 cm H2O in
      PCV and 13+/-2 cm H2O in HFOV. Further, there were no differences in the
      Gruenwald index, protein influx, or ratio of small to large aggregates between
      the study groups. CONCLUSION: PCV with sufficient level of positive end
      expiratory pressure and small driving pressure amplitudes is as effective as HFOV
      to maintain optimal gas exchange, to improve lung mechanics, and to prevent
      protein influx and conversion of large into small aggregates after exogenous
      surfactant therapy in lung-lavaged rats.

PMID- 10966273
TI  - Heparin binding protein increases survival in murine fecal peritonitis.
AB  - OBJECTIVE: To test the effectiveness of recombinant heparin-binding protein
      (HBP), a neutrophil-derived multifunctional protein with monocytic-specific
      properties, in fecal peritonitis and polymicrobial sepsis. DESIGN: Prospective,
      controlled animal trial. SETTING: Animal research laboratory. SUBJECTS: Swiss
      Webster mice challenged with cecal ligation and puncture (CLP) and treated with
      recombinant HBP and 60 mg/kg cefoxitin twice a day. INTERVENTIONS: HBP was
      administered to mice at different concentrations and different intervals before
      and after CLP. Rat albumin (1%) was administered to control animals. MEASUREMENTS
      AND MAIN RESULTS: MORTALITY RATE: Survival was increased in mice pretreated
      intraperitoneally 24 hrs before CLP with 10 microg or 100 microg of HBP without
      cefoxitin (p = .01, Cox-Mantel log-rank test). Compared with control animals,
      survival was increased significantly (from 5% to 47%, p = .014) in mice that
      received cefoxitin and 50 microg ip HBP immediately after CLP, followed by
      continuous administration of HBP (12 microg/24 hrs). Intravenous administration
      of HBP (0.1, 1, and 10 microg) at the time of CLP showed an opposite dose effect;
      low doses (0.1 microg) prolonged early survival, whereas high dose (10 microg)
      shortened survival (p = .036). Compared with control animals, overall survival
      was not different. CHEMOTAXIS: Cytospin preparations from peritoneal exudate
      cells (PECs) 48 hrs after administration of 10 microg and 100 microg ip HBP
      demonstrated a 1.7-fold increase in the total number of macrophages compared with
      carrier control (p < .05). PHAGOCYTOSIS: A flow cytometric in vitro assay
      demonstrated that administration of 10 microg ip HBP alone did not enhance
      phagocytosis of fluorescent Escherichia coli in PECs. However, 24-hr pretreatment
      with 10 microg of HBP followed by CLP increased phagocytosis in PECs 1.8-fold
      compared with the control CLP group (p = .04). RECEPTOR EXPRESSION: CD16/CD32w
      expression in PECs did not change after HBP or CLP. CD11b and CD18 expression in
      PECs was increased significantly after CLP compared with PECs from non-CLP
      challenged animals (p < .05). Pretreatment with 10 microg of HBP did not further
      enhance CD11b/CD18 expression in PECs. CONCLUSIONS: Recombinant HBP increases
      survival in murine fecal peritonitis. The mechanisms by which HBP reduces septic
      death are not fully understood, but they include monocyte chemotaxis and
      increased phagocytosis of E. coli by PECs. Our data suggest that the inflammatory
      response induced by CLP is important for the effect of HBP to enhance
      phagocytosis.

PMID- 10966274
TI  - Accuracy of base excess--an in vitro evaluation of the Van Slyke equation.
AB  - OBJECTIVES: To evaluate the precision, bias and CO2 invariance of base excess as
      determined by the Van Slyke equation over a wide P(CO2) range at normal and low
      hemoglobin concentrations. DESIGN: Prospective in vitro study. SETTING:
      University research laboratory. SUBJECTS: Normal human blood, both undiluted and
      diluted with plasma. INTERVENTIONS: Two experiments were conducted. In the first,
      blood unmodified or after adding HCl or sodium bicarbonate was rendered
      hypercarbic (P(CO2) >70 torr) by gas equilibration. Rapid Pco2 reduction in > or
      =10 steps to a final P(CO2) < or =20 torr was then performed. In the second
      experiment, blood unmodified or diluted to a hemoglobin concentration of
      approximately 4 G% was mixed anaerobically (9:1, vol:vol) with varying
      concentrations of lactic acid in saline (0-250 mmol/L). MEASUREMENTS AND MAIN
      RESULTS: In the first experiment, blood gas analysis at each step during the
      progressive P(CO2) reduction revealed that base excess remained nearly constant
      (SD all specimens < or =0.6 mmol/L) whereas P(CO2) changed by >80 torr. In the
      second experiment, simultaneous blood gas and plasma lactate analyses showed that
      changes in base excess correlated closely with changes in both plasma and whole
      blood lactate concentrations (r2 > or = 0.91) despite concurrent P(CO2)
      elevations as great as 200 torr. Quantification by base excess of change in whole
      blood lactate concentration was precise with slight negative bias (mean negative
      bias, 1.1+/-1.9 mmol/L) in both diluted and undiluted blood. There was
      significant underestimation of change in plasma lactate concentration in
      undiluted blood, presumably because base excess is a whole blood variable.
      CONCLUSIONS: Base excess calculated using the Van Slyke equation accurately
      quantifies metabolic (nonrespiratory) acid-base status in blood in vitro. This
      accuracy is little affected by large simultaneous alterations in P(CO2), or by
      very low hemoglobin concentrations similar to that used to calculate standard
      base excess.

PMID- 10966275
TI  - In vivo measurement of lung capillary-alveolar macromolecule permeability by
      saturation bronchoalveolar lavage.
AB  - OBJECTIVE: Measurement of capillary-alveolar permeability to fluorescein
      isothiocyanate-dextran (FITC-D) (molecular mass, 71,300 daltons) by a sequential
      bronchoalveolar lavage (BAL) technique. DESIGN: Animal research. SETTING: The
      Department of Physiology at a scientific and medical university. SUBJECTS: Nine
      anesthetized and mechanically ventilated dogs. INTERVENTIONS: Two separate
      experiments were performed in each subject-an initial control experiment followed
      by an oleic acid-induced lung injury. The indicator was administered at constant
      blood concentration before serial BAL including eight fluid instillation-recovery
      cycles. MEASUREMENTS: Plasma to BAL solute clearance at saturation (capillary
      alveolar clearance at saturation, mL/min) was calculated and normalized to lavage
      fluid volume (measured by 1251 serum albumin dilution) to obtain a transport rate
      (TR) constant. MAIN RESULTS: TR for FITC-D70 was 4.0+/-0.8 and 46.1+/-18.1 x 10(
      5) x min(-1) in control and injured lung, respectively (p < .02). Capillary
      alveolar clearance of FITC-D70 was not affected by the lavage procedure itself.
      TR reflected essentially epithelial permeability in normal lung and combined
      epithelial and endothelial permeability in injured lung. A significant
      correlation was found between cardiac output and TR in injured lung. CONCLUSIONS:
      Saturation BAL allowed us to estimate capillary-alveolar macromolecule
      permeability in vivo in dogs. Further study may allow bedside evaluation of lung
      injury by BAL in patients.

PMID- 10966276
TI  - Leukocyte-independent plasma extravasation during endotoxemia.
AB  - OBJECTIVES: To determine the meaning of leukocyte-endothelial interactions for
      the development of endotoxin-induced vascular leakage. DESIGN: Randomized,
      blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty
      four male Wistar rats. INTERVENTIONS: After application of fucoidin to prevent
      leukocyte rolling and adherence (25 mg/kg; n = 8; fucoidin/LPS group) or saline
      0.9% (n = 8; LPS group), animals were given an intravenous infusion of endotoxin
      (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals
      in the control group (n = 8) received an equivalent volume of saline 0.9%.
      MEASUREMENTS AND MAIN RESULTS: Leukocyte rolling and leukocyte adherence, red
      cell velocity, vessel diameters, venular wall shear rate, volumetric blood flow,
      and macromolecular leakage were determined in mesenteric postcapillary venules
      using in vivo videomicroscopy at baseline, 60 mins, and 120 mins after start of a
      continuous endotoxin infusion. Fucoidin prevented leukocyte rolling (baseline,
      3+/-2 rollers; 120 mins, 3+/-1 rollers; not significant vs. baseline; p < .01 vs.
      LPS group) and reduced the adherence of leukocytes at baseline and during
      endotoxemia and showed only a slight increase in adherent leukocytes (baseline,
      100+/-38 cells/mm2; 120 mins, 244+/-68 cells/mm2; p < .05 vs. baseline; p < .01
      vs. LPS group). In the LPS group, endotoxin exposure induced a marked increase in
      adherent leukocytes (baseline, 248+/-24 cells/mm2; 120 mins, 560+/-57 cells/mm2;
      p < .01). Leukocyte adherence in control animals (control group) did not increase
      significantly. Macromolecular leakage, expressed as the ratio of perivenular to
      intravenular fluorescence intensity after injection of fluorescence-labeled
      albumin, increased from 0.16+/-0.03 to 0.49+/-0.04 (p < .01 vs. baseline; p < .05
      vs. control) during the infusion of endotoxin in the LPS group. Fucoidin
      application did not diminish the extravasation of albumin (baseline, 0.09+/-0.03;
      120 mins, 0.61+/-0.10; p < .01 vs. baseline; p < .01 vs. control). CONCLUSIONS:
      These results demonstrate that despite a significant reduction of adherent
      leukocytes to the endothelium by fucoidin, there is no reduction in
      macromolecular leakage, indicating that leukocyte-endothelial interactions only
      play a minor role for the development of macromolecular leakage and microvascular
      damage in the early phase of endotoxemia.

PMID- 10966277
TI  - Immune depression in polymicrobial sepsis: the role of necrotic (injured) tissue
      and endotoxin.
AB  - OBJECTIVE: Recent studies suggest immune dysfunction seen after the onset of
      polymicrobial sepsis, as produced by cecal ligation and puncture (CLP), is not
      caused by endotoxin (ETX) alone, but may be caused by the combined effect of the
      necrotic tissue (cecal ligation, [CL]) and other microbial components. Thus, the
      objective of this study was to assess the ability of necrotic tissue, in the
      presence or absence of low-dose endotoxin, to induce changes in the capacity of
      immune cells to produce proinflammatory or anti-inflammatory cytokines
      approximating those seen in CLP. DESIGN: Experimental, prospective study.
      SETTING: A hospital laboratory in the Center for Surgical Research. SUBJECTS:
      Male C3H/HeN mice. INTERVENTIONS: Mice were subjected to a CL and saline infusion
      (CL/Sal), CL in combination with low-dose ETX infusion (CL/ETX) (0.025 mg ETX/25
      g body weight/24 hrs by a peritoneally implanted osmotic mini-pump), ETX infusion
      alone, saline infusion alone (Sal), CLP, or sham-CLP (Sham). Splenocytes, splenic
      macrophage and peritoneal macrophage were harvested from these animals 24 hrs
      (late) after being subjected to the above protocols. Splenocyte and macrophage
      inducible cytokine release was assessed by ELISA/bioassay. Survival over a 7-day
      period was also examined in additional groups. MEASUREMENTS AND MAIN RESULTS: Our
      results indicate a marked decrease in splenic interleukin (IL)-2. In addition,
      peritoneal or splenic macrophage IL-6 productive capacity was depressed in cells
      from animals subjected to CL/ETX or CLP. Alternatively, CL, in the presence or
      absence of ETX, induced a marked change in macrophage cytokine release capacity
      comparable to that seen in CLP, ie, decreased IL-12 release and increased IL-10
      secretion. To the extent these cellular alterations contribute to an increase in
      mortality rate, we observed in subsequent survival studies that neither CL alone
      nor ETX produced mortality. However, the combination of CL/ETX markedly increased
      7-day mortality rate (approximately 33%), although not to the same extent as CLP
      (80%). CONCLUSIONS: These results collectively suggest that the response to
      devitalized tissue produced by cecal ligation may predispose the host to the
      induction of a suppressive macrophage phenotype. The subsequent exposure of these
      animals to microbial agents induces immune dysfunction, as well as mortality seen
      after such a polymicrobial septic challenge.

PMID- 10966278
TI  - Mechanical ventilation in patients with hemispheric ischemic stroke.
AB  - OBJECTIVE: Whether stroke patients should be ventilated mechanically is still a
      contentious issue, because their outcome is very poor. We wanted to investigate
      how often mechanical ventilation is indicated in patients with hemispheric
      ischemic stroke as well as the outcome of these patients and the factors by which
      outcome is influenced. DESIGN: Prospective case series. SETTING: University
      hospital, neurocritical care unit. SUBJECTS: Subjects were 218 patients who met
      the following inclusion criteria: age 18-85 yrs, acute hemispheric ischemic
      infarction, clinical examination, and computed tomography within 6 hrs after the
      onset of symptoms. INTERVENTIONS: Mechanical ventilation was instituted with one
      or more of the following conditions: deterioration of consciousness with the
      inability to protect the airway; PaO2 of <60; P(CO2) of >60 mm Hg; breath rate of
      >40 breaths/min; and left heart insufficiency with definitive or impending
      pulmonary edema. MEASUREMENTS AND MAIN RESULTS: Mechanical ventilation was
      indicated for 52 (24%) of the 218 patients: in 47 (90%) patients because of
      deterioration of consciousness, and in five (10%) patients because of heart
      insufficiency and/or pneumonia. In a logistic regression model, the history of
      hypertension and a size of infarction exceeding two thirds of the middle cerebral
      artery territory were independent variables for the application of mechanical
      ventilation. After 3 months, 42 (81%) of these 52 patients had died. The most
      common cause of death was fatal midbrain herniation caused by complete middle
      cerebral artery infarction. Patients who survived had a good-to-fair outcome.
      CONCLUSIONS: New therapeutic strategies (e.g., hemicraniectomy) must be developed
      to reduce mortality and improve the outcome for this subgroup of ischemic stroke
      patients. Mechanical ventilation is and will remain a crucial element within such
      new concepts.

PMID- 10966279
TI  - Indicators of postpyloric feeding tube placement in children.
AB  - OBJECTIVE: To determine the validity of five indicators (color, pH, and
      concentrations of bilirubin, pepsin, and trypsin in aspirated gastrointestinal
      secretions) in predicting postpyloric placement of feeding tubes in critically
      ill children. DESIGN: Prospective, observational study. SETTING: University
      teaching hospital. PATIENTS: A total of 96 gastrointestinal aspirates were
      obtained from 53 children requiring placement of a nasoenteric feeding tube.
      INTERVENTIONS: Feeding tubes were aspirated by applying suction with a 20-mL
      syringe. Repeat aspirates from the same patient were obtained on different days.
      All aspirations were performed within 30 mins of obtaining a radiograph to assess
      tube position. MEASUREMENTS AND MAIN RESULTS: Aspirates were inspected visually
      for color. pH and bilirubin concentrations were determined at the bedside by
      using reagent strips. Pepsin and trypsin concentrations were measured
      spectrophotometrically in a research laboratory. The sensitivity, specificity,
      predictive values, and efficiency for each indicator and their 95% confidence
      intervals were determined based on the position of the feeding tube on the
      radiograph. Aspirate pH > or =6 had the lowest positive predictive value (76%,
      range 67% to 85%) but high negative predictive value (94%, range 89% to 99%) for
      determining postpyloric positioning of the feeding tube. Bilirubin concentration
      > or =5 mg/dL (> or =86 micromol/L) had the highest positive predictive value
      (96%, range 91% to 100%) and lowest negative predictive value (88%, range 81% to
      95%). Overall efficiency was best for the appearance of a clear yellow aspirate
      color (93%, range 88% to 98%), pepsin concentration < or =20 microg/mL (94%,
      range 89% to 99%), and trypsin concentration > or =50 microg/mL (94%, range 89%
      to 99%). CONCLUSIONS: Simple bedside assessment of gastrointestinal aspirate
      color, pH, and bilirubin concentration is useful for predicting feeding tube
      position. Use of these tests may reduce the number of radiographic studies needed
      to confirm postpyloric positioning. Laboratory-determined pepsin and trypsin
      concentrations predict tube position with a high degree of accuracy. Development
      of simple and inexpensive bedside tests for the detection of gastrointestinal
      enzymes may be useful.

PMID- 10966280
TI  - Comparison of the performance of two general and three specific scoring systems
      for meningococcal septic shock in children.
AB  - OBJECTIVE: To evaluate the performance at admission to the pediatric intensive
      care unit (PICU) of five severity scores, two general (the Pediatric Risk of
      Mortality [PRISM] II and III scores) and three specific for meningococcal septic
      shock (Leclerc, Glasgow Meningococcal Septicemia Prognostic Score [GMSPS], and
      Gedde-Dahl's MOC score) in children with this condition. DESIGN: Multicenter,
      retrospective, cohort study. SETTING: The PICUs from four tertiary centers.
      PATIENTS: Patients were 192 children ranging in age from 1 month to 14 yrs
      consecutively admitted to the participating PICUs during a period of 12 yrs and 6
      months (January 1983 to June 1995), who were diagnosed with presumed or confirmed
      meningococcal septic shock. Patients with a length of stay <2 hrs were excluded
      from the study. INTERVENTIONS: Clinical and laboratory data gathered during the
      first 2 hrs after admission were used to compute the scoring systems tested.
      MEASUREMENTS AND MAIN RESULTS: There were 66 deaths (34%). Neisseria meningitidis
      was cultured from 142 (74%) children. GMSPS and PRISM II provided the best
      discriminative capability, as measured by the area under the receiver operating
      characteristic curve (SEM): 0.816 (0.036) and 0.803 (0.041), respectively. The
      other three scores gave lower receiver operating characteristic areas: PRISM III
      = 0.777 (0.043), MOC = 0.775 (0.037), and Leclerc = 0.661 (0.045). There was a
      statistically significant difference between the areas under the receiver
      operating characteristic curve of GMSPS and Leclerc (p < .01) but not between the
      GMSPS and the remaining three scores. All five scores presented good calibration
      with no significant differences between observed and predicted mortality (Hosmer
      Lemeshow goodness-of-fit test). CONCLUSIONS: The specific GMSPS and the general
      pediatric severity system PRISM II performed better than the other three scores,
      being appropriate tools to assess severity of illness at admission to the PICU in
      children with presumed meningococcal septic shock.

PMID- 10966281
TI  - Comparison of hyperventilation and inhaled nitric oxide for pulmonary
      hypertension after repair of congenital heart disease.
AB  - BACKGROUND: Pulmonary hypertension is associated with congenital heart lesions
      with increased pulmonary blood flow. Acute increases in pulmonary vascular
      resistance (PVR) occur in the postoperative period after repair of these defects.
      These increases in PVR can be ablated by inducing an alkalosis with
      hyperventilation (HV) or bicarbonate therapy. Studies have shown that these
      patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over
      the relative merits and undesirable effects of HV and iNO. HYPOTHESIS: Alkalosis
      and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP)
      in children with pulmonary hypertension after open heart surgery. SETTING:
      Critical care unit of a tertiary care pediatric hospital. DESIGN: Prospective,
      randomized, crossover design. PATIENTS: Twelve children with a mean PAP > 25 mm
      Hg at normal pH after biventricular repair of congenital heart disease.
      INTERVENTIONS: Patients were assigned to receive iNO or HV (pH > 7.5) in random
      order, and the effect on hemodynamics was measured. Each treatment was
      administered for 30 mins with a 30-min washout period between treatments.
      Finally, both treatments were administered together to look for a possible
      additive effect. MEASUREMENTS AND MAIN RESULTS: Cardiac output and derived
      hemodynamic parameters using the dye dilution technique. Hyperventilation,
      achieved by an increase in ventilator rate without a change in mean airway
      pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg
      and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both
      pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous
      pressure, and cardiac output and an increase in systemic vascular resistance. In
      comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was
      comparable between treatments, although addition of iNO to HV resulted in a small
      additional reduction in PVR. An additional decrease in PAP was seen when HV was
      added to iNO, attributable to a reduction in cardiac output rather than a further
      decrease in PVR. CONCLUSIONS: Inhaled NO and HV are both effective at lowering
      PAP and PVR in children with pulmonary hypertension after repair of congenital
      heart disease. The selective action of iNO on the pulmonary circulation offers
      advantages over HV because a decrease in cardiac output and an increase in SVR
      are undesirable in the postoperative period.

PMID- 10966283
TI  - Combining physician's subjective and physiology-based objective mortality risk
      predictions.
AB  - OBJECTIVE: None of the currently available physiology-based mortality risk
      prediction models incorporate subjective judgements of healthcare professionals,
      a source of additional information that could improve predictor performance and
      make such systems more acceptable to healthcare professionals. This study
      compared the performance of subjective mortality estimates by physicians and
      nurses with a physiology-based method, the Pediatric Risk of Mortality (PRISM)
      III. Then, healthcare provider estimates were combined with PRISM III estimates
      using Bayesian statistics. The performance of the Bayesian model was then
      compared with the original two predictions. DESIGN: Concurrent cohort study.
      SETTING: A tertiary pediatric intensive care unit at a university affiliated
      children's hospital. PATIENTS: Consecutive admissions to the pediatric intensive
      care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each of the
      642 consecutive eligible patients, an exact mortality estimate and the degree of
      certainty (continuous scale from 1 to 5) associated with the estimate was
      collected from the attending, fellow, resident, and nurse responsible for the
      patient's care. Bayesian statistics were used to combine the PRISM III and
      certainty weighted subjective predictions to create a third Bayesian estimate of
      mortality. PRISM III discriminated survivors from nonsurvivors very well (area
      under curve [AUC], 0.924) as did the physicians and nurses (AUCs attendings,
      0.953; fellows, 0.870; residents, 0.923; nurses, 0.935). Although the AUCs of the
      healthcare providers were not significantly different from the AUCs of PRISM III,
      the Bayesian AUCs were higher than both the healthcare providers' AUCs (p < or =
      .09 for all) and PRISM III AUCs. Similarly, the calibration statistics for the
      Bayesian estimates were superior to the calibration statistics for both the
      healthcare providers and PRISM III models. CONCLUSIONS: The results of this study
      demonstrated that healthcare providers' subjective mortality predictions and
      PRISM III mortality predictions perform equally well. The Bayesian model that
      combined provider and PRISM III mortality predictions was more accurate than
      either provider or PRISM III alone and may be more acceptable to physicians. A
      methodology using subjective outcome predictions could be more relevant to
      individual patient decision support.

PMID- 10966282
TI  - A myocardial cytotoxic process is involved in the cardiac dysfunction of
      meningococcal septic shock.
AB  - OBJECTIVE: Myocardial dysfunction is a characteristic component of meningococcal
      septic shock and contributes to the persisting high mortality from the disease.
      Specific treatment of the myocardial failure has been hampered by the lack of
      understanding of its pathophysiology. We were interested to determine whether
      myocardial cell death was occurring in the presence of meningococcal septicemia
      and whether it correlated with the degree of left ventricular dysfunction and
      disease severity. We therefore investigated the release of cardiac troponin I
      (cTnI), a sensitive and specific marker of myocardial cell death, and related
      this to the severity of disease and cardiac dysfunction. DESIGN: Prospective
      study SETTING: Pediatric intensive care unit SUBJECTS: Patients admitted to the
      pediatric intensive care unit with a diagnosis of meningococcal septicemia.
      INTERVENTIONS: Serum concentrations of cTnI were determined at admission to
      intensive care in 101 children with meningococcal septicemia and serially in 37
      children. Changes in cTnI were related to disease severity as measured by the
      Pediatric Risk of Mortality score and two markers of cardiac dysfunction.
      MEASUREMENTS AND MAIN RESULTS: Serum concentrations of cTnI were elevated above
      the range for healthy children in 24% of children with meningococcal septicemia
      at admission and in 62% of patients within 48 hrs. The peak concentrations
      occurred between 12 and 36 hrs after admission. There were significant
      correlations between cTnI levels and disease severity and between cTnI levels and
      the degree of myocardial depression measured by quantitative transthoracic
      echocardiography and peak inotrope requirements. CONCLUSIONS: The elevated serum
      concentrations of cTnI indicate that myocardial cell death is occurring in
      meningococcal septicemia. The relationship between cTnI and markers of myocardial
      function suggest that the cell death may have a role in the pathogenesis of
      myocardial dysfunction in meningococcal septicemia. Elucidation of the mechanism
      responsible for myocardial injury may lead to the development of therapeutic
      interventions to prevent or limit this cardiac damage.

PMID- 10966284
TI  - Validation of predictors of extubation success and failure in mechanically
      ventilated infants and children.
AB  - OBJECTIVE: To validate predictors of extubation success and failure in
      mechanically ventilated infants and children by using bedside measures of
      respiratory function. DESIGN: Prospective, descriptive study. SETTING: A
      university-affiliated children's hospital with a 51-bed critical care area.
      PATIENTS: All infants and children who were mechanically ventilated for > or =24
      hrs except neonates < or =37 wks gestation and patients with neuromuscular
      disease. INTERVENTIONS: None. MEASUREMENTS AND METHODS: Extubation failure was
      defined as reintubation within 48 hrs of extubation in the absence of upper
      airway obstruction. Failure rates were calculated for different ranges (selected
      a priori of preextubation measures of breathing effort, ventilator support,
      respiratory mechanics, central inspiratory drive, and integrated indices useful
      in adults. Effort of spontaneous breathing was assessed by the respiratory rate
      standardized to age, the presence of retractions and paradoxic breathing,
      inspiratory pressure, maximal negative inspiratory pressure, ratio of inspiratory
      pressure to maximal negative inspiratory pressure, and tidal volume indexed to
      body weight of a spontaneous breath. Ventilator support was measured by F(IO2),
      mean airway pressure, oxygenation index, and the fraction of total minute
      ventilation provided by the ventilator. Respiratory mechanics was assessed by
      peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory
      drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and
      the CROP (compliance, rate, oxygenation, and pressure) indexed to body weight,
      the integrated indices useful in predicting extubation failure in adults, were
      also calculated. A regression test for a linear trend in proportions was
      performed with preselected ranges and the corresponding failure rates. The
      failure rates from this study (validation group) were compared to those published
      previously (prediction group) by the chi-square test for proportions. The
      distribution of categorical variables between groups was analyzed by using the
      chi-square test or the Fisher's exact test, and p < .05 was considered
      significant. MAIN RESULTS: The study involved 312 patients. There were no
      differences in any of the clinical characteristics between the prediction and
      validation groups. The reasons for reintubation were similar in both groups.
      Preextubation data were also similar between the two groups. There were no
      differences between the prediction and the validation groups in failure rates
      with different ranges. There were no differences in the failure rates for any of
      the cutoff values for peak ventilatory inspiratory pressure, mean airway
      pressure, F(IO2), oxygenation index, dynamic compliance, tidal volume indexed to
      body weight of a spontaneous breath, fraction of total minute ventilation
      provided by the ventilator, and mean inspiratory flow. CONCLUSIONS: Bedside
      measures of respiratory function can predict extubation success and failure in
      infants and children. Both a low risk and a high risk of failure can be
      determined by using these measures. Integrated indices useful in adults do not
      reliably predict extubation success or failure in infants and children. Our study
      validates our previously published study.

PMID- 10966286
TI  - Increased excretion of urinary glycosaminoglycans in meningococcal septicemia and
      their relationship to proteinuria.
AB  - OBJECTIVES: Meningococcal septic shock is a devastating illness associated with
      an increase in vascular permeability leading to hypovolemia and accumulation of
      plasma proteins and fluid in tissues. The capillary leak syndrome is often
      associated with widespread thrombosis in the skin, limbs, and digits. We
      postulated that the increase in vascular permeability and the intravascular
      thrombosis might be caused by an inflammation-induced loss of endothelial and
      basement membrane glycosaminoglycans (GAGs), which play a role in the
      permeability and thromboresistant properties of the microvasculature. DESIGN:
      Prospective, single-center observational study. SETTING: University-affiliated
      meningococcal research unit and pediatric intensive care unit. PATIENTS: Eighteen
      children requiring intensive care for meningococcal sepsis, 18 children with
      steroid-responsive nephrotic syndrome, and 18 healthy control children.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum concentrations and
      urine excretion of glycosaminoglycans were measured and related to changes in
      glomerular permeability to plasma proteins. The size-distribution and nature of
      glycosaminoglycans were defined by Polyacrylamide Gel Electrophoresis and
      specific enzyme digestion. Urinary excretion of heparan sulfate, chondroitin-4
      sulfate, and chondroitin-6-sulfate were significantly increased in meningococcal
      disease (MD) relative to healthy controls and children with steroid-responsive
      nephrotic syndrome. The urinary GAGs in MD were of similar size to those in
      controls when analyzed after pronase digestion. However, analysis of proteoglycan
      size before proteolytic digestion showed the urinary GAGs in MD were of lower
      molecular weight and unattached to proteins. The fractional excretion of albumin
      and immunoglobulin G in MD increased with severity of disease. Patients with
      severe or fatal MD had albumin clearances overlapping those seen in steroid
      responsive nephrotic syndrome. There was a significant correlation between
      proteinuria in MD and urinary excretion of heparan sulfate (r2 = 0.611, p <
      .0001), chondroitin-4-sulfate (r2 = 0.721, p < .0001), and chondroitin-6-sulfate
      (r2 = 0.395, p < .0001). CONCLUSIONS: The capillary leak in meningococcal disease
      is associated with increased plasma and urine concentrations of GAGs, which may
      be proteolytically cleaved from endothelial and basement membrane sites. The
      correlation between the severity of protein leakage and the urine excretion of
      GAGs suggests that loss of GAGs may be causally related to the increase in
      permeability to proteins.

PMID- 10966285
TI  - Transthoracic intracardiac catheters in pediatric patients recovering from
      congenital heart defect surgery: associated complications and outcomes.
AB  - OBJECTIVES: To characterize transthoracic intracardiac catheter uses and
      associated morbidities in pediatric patients recovering from congenital heart
      defect surgery and to identify potential risk factors associated with their use.
      DESIGN: Prospective data collection and review. SETTING: An 18-bed pediatric
      intensive care unit (PICU) in a tertiary care university hospital. PATIENTS: All
      pediatric patients between October 1, 1996, and September 30, 1997, who were
      recovering from congenital heart defect surgery and had transthoracic
      intracardiac catheters in place. MEASUREMENTS AND MAIN RESULTS: Catheter use,
      associated morbidity, necessary interventions, and risk factors for complications
      of catheter use were identified. During this period, 523 catheters (276 right
      atrial, 155 left atrial, 68 common atrial, and 24 right ventricular or pulmonary
      artery catheters) in 351 PICU patients were studied. Mean age was 23.1+/-45.1
      months (median, 4.98 months); 138 patients (39.3%) were <3 months old. The rate
      of occurrence of bleeding with catheter removal (mediastinal output in the hour
      after removal that was more than twice the previous average hourly output) was
      36.7%, and bleeding occurred more frequently with left atrial catheters (47%;
      odds ratio, 2.0; p < .05). However, interventions after catheter removal were
      required for only 8.3% (42/504) of catheters removed, and hemodynamic compromise
      occurred with the removal of only 2.6% (13/504) of catheters. Interventions
      included fluid resuscitation (35 cases), pleural drainage (three cases), catheter
      wiring for retention (one case), chest tube suctioning (two cases), and surgical
      removal (one case). No associated deaths occurred. In a multivariate logistic
      regression analysis, age <3 months (odds ratio, 4.74), catheter location (left
      atrial: odds ratio, 4.97; pulmonary artery: odds ratio, 12.48), and platelet
      count of <50,000 (odds ratio, 8.59) were identified as risk factors associated
      with a need for intervention after catheter removal (p < .05). Other
      complications included blood cultures positive for organisms (1.5%), thrombus
      (0.6%), and catheter nonfunction (10.9%). Prematurity was a risk factor for
      thrombus and nonfunction. CONCLUSIONS: Use of transthoracic intracardiac
      catheters in pediatric patients is safe. Young infants and pediatric patients
      with thrombocytopenia or with catheters in the left atrial or pulmonary artery
      position have a greater need for interventions after catheter removal, warranting
      added precautions.

PMID- 10966287
TI  - Development of a survey to measure parent satisfaction in a pediatric intensive
      care unit.
AB  - OBJECTIVE: To use classic survey methodology to develop a specific survey tool
      that can assess parent satisfaction with medical care in a pediatric intensive
      care setting. DESIGN: Application of survey design methodology to develop and
      analyze a parent satisfaction survey. SETTING: A pediatric intensive care unit
      (PICU) in a large teaching hospital. SUBJECTS: Sixty-six parents of children
      admitted to a PICU. RESULTS: A four-stage process of item selection, item
      reduction, pretesting, and test analysis was used to create a 23-item parent
      satisfaction survey that was statistically analyzed and developed specifically
      for the PICU setting. The survey tool was developed with the input of parents of
      children admitted to a PICU, and it was administered to parents in the PICU. The
      resultant survey was analyzed for validity and reliability. Both test-retest and
      internal consistency reliability were evaluated. This design yielded a survey
      with acceptable reliability, as demonstrated by a reliability coefficient of
      0.8275. Test-retest reliability also showed good correlation of answers. Validity
      was partially established by including parents in the identification of survey
      topics. CONCLUSIONS: Classic survey design methodology was applied to develop a
      specific satisfaction survey in a pediatric inpatient setting. This stepwise
      method yielded a parent survey specific to one type of inpatient unit, and the
      resultant survey tool reliably measured levels of parent satisfaction with
      medical care in that area. This study demonstrates the feasibility of applying
      classic survey methodology to develop a statistically analyzed parent
      satisfaction survey for an inpatient setting.

PMID- 10966289
TI  - Pathophysiology of septic encephalopathy: a review.
AB  - OBJECTIVES: Encephalopathy is a common complication of sepsis. This review
      describes the different pathologic mechanisms that may be involved in its
      etiology. DATA SOURCES: The studies described here were derived from the database
      PubMed (http:??www.nlm.nih.gov) and from references identified in the
      bibliographies of pertinent articles and books. The citations are largely
      confined to English language articles between 1966 and 1998. Older publications
      were used if they were of historical significance. STUDY SELECTION: All
      investigations in which any aspect of septic encephalopathy was reported were
      included. This selection encompasses clinical, animal, and in vitro cell culture
      work. DATA EXTRACTION: The literature cited was published in peer-reviewed
      clinical or basic science journals or in books. DATA SYNTHESIS: Contradictions
      between the results of published studies are discussed. CONCLUSIONS: The most
      immediate and serious complication of septic encephalopathy is impaired
      consciousness, for which the patient may require ventilation. The etiology of
      septic encephalopathy involves reduced cerebral blood flow and oxygen extraction
      by the brain, cerebral edema, and disruption of the blood-brain barrier that may
      arise from the action of inflammatory mediators on the cerebrovascular
      endothelium, abnormal neurotransmitter composition of the reticular activating
      system, impaired astrocyte function, and neuronal degeneration. Currently, there
      is no treatment.

PMID- 10966288
TI  - Accuracy of an indirect calorimeter for mechanically ventilated infants and
      children: the influence of low rates of gas exchange and varying FIO2.
AB  - OBJECTIVE: To test the accuracy and validity of the Deltatrac II MBM-200
      metabolic monitor for use in mechanically ventilated infants and children in the
      pediatric intensive care unit. DESIGN: Laboratory validation of an indirect
      calorimeter with a ventilated lung model. The influence of low tidal volumes and
      low levels of oxygen consumption (V(O2)) and carbon dioxide production (V(CO2))
      in combination with different levels of inspired oxygen concentrations (F(IO2))
      was investigated. SETTING: University research laboratory. SUBJECTS: Low tidal
      volumes were provided with two intermittent flow types of ventilators, a Servo
      300 and a Servo 900C. INTERVENTIONS: A butane flame with a V(O2) approximating 20
      mL/min and 40 mL/min was ventilated. To investigate the effect of different
      levels of F(IO2) on the accuracy of V(O2), V(CO2), and respiratory quotient (RQ),
      measurements were performed at F(IO2) target values of 0.25, 0.40, and 0.60.
      MEASUREMENTS AND MAIN RESULTS: No significant differences were found between the
      ventilators regarding V(O2), V(CO2), and RQ measurements. The mean deviation of
      V(O2) increased significantly with increasing F(IO2) to -7.98% with a V(O2) of
      21.0 mL/min and to -8.46% with a V(O2) of 38.9 mL/min (F(IO2), 0.558) with a
      variability (2 SD) of +/- 4.86% and +/- 6.82%, respectively. The mean deviation
      and variability of V(CO2) in all tests remained within 8%. The mean deviation of
      RQ increased significantly with increasing F(IO2) to 5.5% with a V(O2) of 21.0
      mL/min and to 5.69% with a V(O2) of 38.9 mL/min (F(IO2), 0.558) with a
      variability (2 SD) of +/- 5.62% and +/- 5.76%, respectively. The minute to minute
      delivered F(IO2) fluctuated significantly when increasing the level of F(IO2).
      CONCLUSIONS: The Deltatrac II MBM-200 metabolic monitor appears accurate for low
      levels of V(O2) and V(CO2) during mechanical ventilation with F(IO2) levels up to
      0.390. With increasing F(IO2) to 0.558, the increase in deviation of V(O2) for
      single measurements can be of clinical relevance for mechanically ventilated
      infants and children. The increased fluctuation of delivered F(IO2) on higher
      levels of F(IO2) is likely the cause of the inaccuracy.

PMID- 10966290
TI  - Hemoglobin solutions--not just red blood cell substitutes.
AB  - OBJECTIVE: To review current knowledge about cell-free hemoglobin solutions. DATA
      SOURCES: All studies involving cell-free hemoglobin were retrieved from a
      computerized MEDLINE search from 1980 to 1998. We also reviewed the reference
      lists of all available review articles and primary studies to identify references
      not found in the computerized search. STUDY SELECTION: Clinical and experimental
      studies in which cell-free hemoglobin solutions were studied. DATA EXTRACTION:
      From the selected studies, information was obtained regarding the experimental
      model or the study population in which cell-free hemoglobin solutions were
      investigated, the type of cell-free hemoglobin solution, their deleterious or
      beneficial effects, and their possible indications. DATA SYNTHESIS: In many
      studies, hemoglobin solutions were considered as efficient resuscitative agents
      and good alternatives to red blood cell transfusion, because of their marked
      vasopressor effect coupled with their capacity to improve the microcirculation
      and quickly restore metabolic parameters. Nevertheless, potential problems
      include an increased susceptibility to infection, immunosuppression, oxidative
      damage, excessive pulmonary and systemic vasoconstriction, and platelet
      activation. CONCLUSIONS: Hemoglobin solutions are more than mere blood
      substitutes. Promising effects on oxygen transport and the microcirculation need
      to be confirmed, and the results of continuing research are eagerly awaited.

PMID- 10966291
TI  - Proposing a new standard to establish medical competence for the purpose of
      critical care intervention.

PMID- 10966292
TI  - Guidelines for the use of do-not-resuscitate orders in Dutch hospitals.
AB  - OBJECTIVES: To determine the prevalence and analyze the content of guidelines for
      the use of do-not-resuscitate (DNR) orders in Dutch hospitals. DESIGN: Cross
      sectional descriptive study. MEASUREMENTS AND MAIN RESULTS: A questionnaire was
      mailed to the directors of patient care at all 143 Dutch hospitals. Directors
      were asked whether their hospitals had guidelines for the use of DNR orders and
      to provide copies of the guidelines if they did. The content of the guidelines
      was analyzed with regard to basic assumptions about nonresuscitation,
      definitions, persons involved in decision-making, advance directives, starting
      discussions about nonresuscitation, notation, evaluation, and other aspects. Of
      the 143 hospital directors surveyed, 95% responded. Sixty percent of the
      hospitals had guidelines for the use of DNR orders and provided copies. The
      assumption "always resuscitate, unless" was mentioned in 66% of guidelines. In
      93% it was stated that patients should be involved in decision-making about
      nonfutile resuscitation. In 38% it was stated that in principle, living wills
      were respected in cases of incompetence. The role of proxies was mainly to
      discuss decisions (58% of guidelines), not to make them. The most frequently
      mentioned moment for starting a discussion about nonresuscitation was the onset
      of clinical deterioration of the patient (41%). CONCLUSIONS: It is promising that
      60% of Dutch hospitals have developed guidelines for the use of DNR orders.
      However, current guidelines can be improved in many respects.

PMID- 10966293
TI  - Half the families of intensive care unit patients experience inadequate
      communication with physicians.
AB  - OBJECTIVE: Effective communication of simple, clear information to families of
      intensive care unit (ICU) patients is a vital component of quality care. The
      purpose of this study was to identify factors associated with poor comprehension
      by family members of the status of ICU patients. DESIGN: Prospective study.
      SETTING: University-affiliated medical intensive care unit. PATIENTS AND METHODS:
      A total of 102 patients admitted to an ICU for >2 days. INTERVENTION: The
      representatives of 76 patients who were visited by at least one person during
      their ICU stay were interviewed. RESULTS: Mean patient age was 54+/-17 yrs and
      mean Simplified Acute Physiology Score II at admission was 40+/-20. The
      representative was the spouse in 47 cases (62%). Among representatives, 25 (33%)
      were of foreign descent and 12 (16%) did not speak French. Mean duration of the
      first meeting with a physician was 10+/-6 mins. In 34 cases (54%), the
      representative failed to comprehend the diagnosis, prognosis, or treatment of the
      patient. Factors associated with poor comprehension by representatives included
      patient-related, family-related, and physician-related factors. Patient-related
      factors included age <50 yrs (p = .03), unemployment (p = .01), referral from a
      hematology or oncology ward (p = .006), admission for acute respiratory failure
      (p = .005) or coma (p = .01), and a relatively favorable prognosis (p = .04).
      Family-related factors were foreign descent (p = .007), no knowledge of French (p
      = .03), representative not the spouse (p = .03), and no healthcare professional
      in the family (p = .01). Physician-related factors were first meeting with
      representative <10 mins (p = .03) and failure to give the representative an
      information brochure (p = .02). Moreover, after the first meeting, caregivers
      accurately predicted poor comprehension by representatives (p = .03).
      CONCLUSIONS: Patient information is frequently not communicated effectively to
      family members by ICU physicians. Physicians should strive to identify patients
      and families who require special attention and to determine how their personal
      style of interrelating with family members may impair communication.

PMID- 10966294
TI  - 100 thoughts for the critical care practitioner in the new millennium.

PMID- 10966295
TI  - Prior healthcare utilization as a predictor of survival for medical intensive
      care unit patients.
AB  - OBJECTIVE: To determine whether measures of inpatient care utilization from the
      year preceding admission to a medical intensive care unit (MICU) improve
      physiology-based predictions of hospital and 1-yr survival. DESIGN: Inception
      cohort study with a validation cohort. SETTING: The MICU in university-affiliated
      Department of Veterans Affairs Medical Center. PATIENTS: A total of 1,200
      consecutive patients admitted to the MICU. MEASUREMENTS AND MAIN RESULTS:
      Increased use of inpatient health care before MICU admission was associated with
      increased mortality. However, inpatient utilization data failed to improve
      physiology-based logistic models for hospital and 1-yr survival (p > .15 for
      improvement in the area under the receiver operating characteristic curve for
      both end points in the validation cohort), whereas physiologic data improved
      models derived from measures of inpatient care (p < .001 for both end points).
      Empirically derived inpatient care models used only information from the few days
      preceding MICU admission, despite the availability of a full year of data.
      CONCLUSIONS: Chronic illness, as gauged by a need for frequent inpatient care in
      the year before MICU admission, is not independently predictive of poor short- or
      long-term survival. Clinicians should not attempt to predict survival of
      prospective MICU patients by the extent of previous inpatient care.

PMID- 10966296
TI  - End-of-life care in the pediatric intensive care unit after the forgoing of life
      sustaining treatment.
AB  - OBJECTIVE: To describe the attitudes and practice of clinicians in providing
      sedation and analgesia to dying patients as life-sustaining treatment is
      withdrawn. STUDY DESIGN: Prospective case series of 53 consecutive patients who
      died after the withdrawal of life-sustaining treatment in the pediatric intensive
      care unit at three teaching hospitals in Boston. Data on the reasons why
      medications were given were obtained from a self-administered anonymous
      questionnaire completed by the critical care physician and nurse for each case.
      Data on what medications were given were obtained from a review of the medical
      record. RESULTS: Sedatives and/or analgesics were administered to 47 (89%)
      patients who died after the withdrawal of life-sustaining treatment. Patients who
      were comatose were less likely to receive these medications. Physicians and
      nurses cited treatment of pain, anxiety, and air hunger as the most common
      reasons, and hastening death as the least common reason, for administration of
      these medications. Hastening death was viewed as an "acceptable, unintended side
      effect" of terminal care by 91% of physician-nurse matched pairs. The mean dose
      of sedatives and analgesics administered nearly doubled as life-support was
      withdrawn, and the degree of escalation in dose did not correlate with
      clinician's views on hastening death. CONCLUSION: Clinicians frequently escalate
      the dose of sedatives or analgesics to dying patients as life-sustaining
      treatment is withdrawn, citing patient-centered reasons as their principle
      justification. Hastening death is seen as an unintended consequence of
      appropriate care. A large majority of physicians and nurses agreed with patient
      management and were satisfied with the care provided. Care of the dying patient
      after the forgoing of life-sustaining treatment remains underanalyzed and needs
      more rigorous examination by the critical care community.

PMID- 10966297
TI  - Teaching critical appraisal during critical care fellowship training: a
      foundation for evidence-based critical care medicine.
AB  - OBJECTIVE: To determine whether fellowship training in critical care medicine
      with critical appraisal exercises improves the ability and confidence of fellows
      to evaluate the medical literature. DESIGN: Prospective, interventional pilot
      study. SETTING: Multidisciplinary critical care medicine training program at a
      large university hospital. INTERVENTION: Fellows were given three didactic
      sessions covering study design, analysis, and critical appraisal techniques.
      During the course of the year, each fellow was required to review one article
      from the literature and present a critique of this article to the group and
      faculty (Journal Club). Fellows were guided in the preparation of this
      presentation by one of the critical care medicine faculty. Finally, a written
      analysis and critique of the article was performed by each fellow. MEASUREMENTS
      AND MAIN RESULTS: A test was given to each fellow at the beginning and end of the
      academic year. This test consisted of two pairs of articles on therapy for acute
      lung injury. For the pretest, each fellow was assigned, at random, one pair of
      articles. Fellows were given 1 hr to review both articles and to fill out a six
      point test to assess their ability and confidence to appraise each article. At
      the end of the year, each fellow was tested on the opposite pair, the tests were
      graded in a blinded fashion and the results of each test were compared. Six
      fellows completed both pre- and posttests. These paired results were analyzed
      separately, whereas results for another six fellows were conducted as an unpaired
      analysis. Mean scores increased both for the paired analysis (4.1+/-0.7 vs. 5.1+/
      0.5; p = .015) and for the unpaired analysis (4.3+/-0.6 vs. 5.0+/-0.5; p = .012).
      Self-reported confidence in critical appraisal also increased (2.5+/-0.5 vs.
      3.9+/-0.7; p = .004 and 2.6+/-0.5 vs. 3.9+/-0.6; p < .001, respectively).
      CONCLUSION: Critical appraisal exercises used in the training of critical care
      medicine fellows appear to improve both ability and confidence to appraise
      relevant medical literature.

PMID- 10966298
TI  - Death related to propofol use in an adult patient.
AB  - OBJECTIVE: To report an adult trauma patient fatality related to propofol
      administration. DESIGN: Retrospective case review. SETTING: Trauma intensive care
      unit (ICU) in a level one trauma center. PATIENT: An 18-yr-old man involved in a
      motor vehicle crash. INTERVENTIONS: Treatment for multiple trauma injuries and
      propofol sedation. MEASUREMENTS AND MAIN RESULTS: Posttrauma ICU monitoring was
      performed. The patient developed cardiac arrhythmia, metabolic acidosis, and
      cardiac failure, which resulted in death. CONCLUSION: Death related to propofol
      infusion can occur in adults as well as in pediatric patients.

PMID- 10966299
TI  - Feasibility of asynchronous independent lung high-frequency oscillatory
      ventilation in the management of acute hypoxemic respiratory failure: a case
      report.
AB  - OBJECTIVE: To report the first case of the use of asynchronous independent lung
      high-frequency oscillatory ventilation (AIL-HFOV) in the management of acute
      hypoxemic respiratory failure in a large pediatric patient with markedly
      asymmetric lung disease. DESIGN: Case study. SETTING: Tertiary pediatric
      intensive care unit in a pediatric teaching hospital. PATIENT: A 17-yr-old, 87-kg
      male patient with trisomy 21 and with respiratory failure and progressive
      hypoxemia because of pneumonia. INTERVENTIONS: Intubation with a 37-Fr double
      lumen endobronchial tube and ventilation with two oscillatory ventilators for a
      total of 16 days. MEASUREMENTS AND MAIN RESULTS: Hemodynamic data were obtained
      using a pulmonary artery catheter. Adequate oxygenation and ventilation were
      readily achieved after institution of AIL-HFOV. The F(IO2)/PaO2 ratio increased
      from 52 to 224, and the shunt fraction decreased from 40 to 9 after 30 mins of
      AIL-HFOV. F(IO2) was rapidly reduced from 1.0 to 0.4 on the right lung and to 0.6
      on the left lung. Mean arterial pressure was maintained, the cardiac index
      increased from 3.5 to 5.4 L/min/m2, the systemic vascular resistance index
      decreased from 1513 to 1225 dyne x sec/cm5 x m2, and the pulmonary vascular
      resistance index decreased from 723 to 428 dyne x sec/cm5 x m2 without the need
      for additional fluid boluses or increases in inotropic support. No airleaks
      developed during the entire hospital stay. CONCLUSIONS: AIL-HFOV improved
      oxygenation and hemodynamic performance in this large patient. This case
      demonstrates that it is feasible to use two high-frequency oscillatory
      ventilators to independently ventilate the lungs of a large patient with markedly
      asymmetric lung disease. We believe that AIL-HFOV deserves future study and
      development for the treatment of large patients with acute hypoxemic respiratory
      failure and asymmetric lung disease when other choices are limited.

PMID- 10966300
TI  - Modulation of gene expression in critical illness: a new millennium or a brave
      new world?

PMID- 10966301
TI  - Research on postresuscitation myocardial dysfunction: potential limitations of
      isolated perfused heart models.

PMID- 10966302
TI  - Gram-positive sepsis.

PMID- 10966303
TI  - Increasing arterial oxygenation with knobs and tricks: lipstick cosmetics or real
      improvement of outcome?

PMID- 10966304
TI  - Back to the future: is lipid A an appropriate target for the therapy of sepsis?

PMID- 10966305
TI  - Heliox in chronic obstructive pulmonary disease...time to lighten up?

PMID- 10966306
TI  - "For every complex problem, there is a solution that is simple...and wrong".

PMID- 10966308
TI  - Adequate empirical therapy minimizes the impact of diagnostic methods in patients
      with ventilator-associated pneumonia.

PMID- 10966307
TI  - Gene in a haystack: tumor necrosis factor polymorphisms and outcome in sepsis.

PMID- 10966309
TI  - Prolonged mechanical ventilation after cardiac surgery: diagnosis of a better
      prognosis.

PMID- 10966310
TI  - Norepinephrine: no more "leave 'em dead"?

PMID- 10966311
TI  - Anemia of the critically ill: "acute" anemia of chronic disease.

PMID- 10966312
TI  - Severe chronic disease with acute physiologic disturbance: a role for intensive
      care.

PMID- 10966313
TI  - Can pure oxygen prevent stroke damage?

PMID- 10966314
TI  - In quest of optimal resuscitation: tissue specific, on to the microcirculation.

PMID- 10966315
TI  - Ranitidine: defining the big picture.

PMID- 10966316
TI  - Cerebral blood flow promotion after prolonged cardiac arrest.

PMID- 10966317
TI  - Vasoactive agents and the gut: fueling the motor of multiple organ failure.

PMID- 10966318
TI  - Leukocytes in sepsis: do they just keep rolling along?

PMID- 10966319
TI  - Resuscitation access and assessment: recurring themes of the intraosseous route.

PMID- 10966320
TI  - Myocardial depression versus myocardial destruction: integrating the multiple
      mechanisms of myocardial dysfunction during sepsis.

PMID- 10966321
TI  - Handicapping outcome.

PMID- 10966322
TI  - New standards for patient rights and medical competence.

PMID- 10966323
TI  - ICU: ineffective communication unit.

PMID- 10966324
TI  - Intensive care unit outcomes: healthcare utilization versus physiology.

PMID- 10966325
TI  - Withdrawing mechanical ventilation in children.

PMID- 10966326
TI  - Extubation or euthanasia: getting the facts clear.

PMID- 10966327
TI  - End-of-life in the pediatric intensive care unit: seeking the family's decision
      of when and how, not if.

PMID- 10966328
TI  - Origins of the Motor Activity Assessment Scale score: a multi-institutional
      process.

PMID- 10966329
TI  - Scoring systems and severe acute pancreatitis.

PMID- 10966330
TI  - Effects of 21-aminosteroids on tumor necrosis factor-alpha in endotoxemia.

PMID- 10966331
TI  - Syndrome of inappropriate antidiuretic hormone secretion after spinal surgery in
      children.

PMID- 10966332
TI  - Microcirculatory weak units--an alternative explanation.

PMID- 10966333
TI  - Sublingual PCO2.

PMID- 10966334
TI  - How to detect Helicobacter pylori infection in the critically ill patient?

PMID- 10966335
TI  - Is Helicobacter pylori associated with gastrointestinal bleeding after cardiac
      surgery?

PMID- 10966336
TI  - Not all perfluorochemicals are created equal.

PMID- 10966337
TI  - A short stay or 23-hour ward in a general and academic children's hospital: are
      they effective?
AB  - OBJECTIVE: We evaluated the usefulness of a short stay or 23-hour ward in a
      pediatric unit of a large teaching hospital, Westmead Hospital, and an academic
      Children's hospital, The New Children's Hospital, to determine if they are a
      useful addition to the emergency service. METHODS: This is a descriptive
      comparison of prospectively collected data on all children admitted to the short
      stay ward at Westmead Hospital (WH) during 1994 and the short stay ward at the
      New Children's Hospital (NCH) during 1997-98. These hospitals service an
      identical demographic area with the latter (NCH) a tertiary referral center. The
      following outcome measures were used: length of stay, appropriateness of stay,
      rate of admission to an in-hospital bed, and rate of unscheduled visits within 72
      hours of discharge. Adverse events were reported and patient follow-up was
      attempted at 48 hours after discharge in all cases. RESULTS: The short stay ward
      accounted for 10.3% (Westmead Hospital) and 14.7% (New Children's Hospital) of
      admissions, with 56% medical in nature, 30% surgical, and the remainder
      procedural or psychological. Admission patterns were similar, with asthma,
      gastroenteritis, convulsion, pneumonia, and simple surgical conditions accounting
      for most short stay ward admissions. The short stay ward increased hospital
      efficiency with an average length of stay of 17.5 hours (Westmead Hospital)
      compared to 20.5 hours (New Children's Hospital). The users of the short stay
      ward were children of young age less than 2 years, with stay greater than 23
      hours reported in only 1% of all admissions to the short stay ward. The rate of
      patient admission to an in-hospital bed was low, (4% [Westmead Hospital] compared
      to 6% [New Children's Hospital]), with the number of unscheduled visits within 72
      hours of short stay ward discharge less than 1%. There were no adverse events
      reported at either short stay ward, with parental satisfaction high. The short
      stay ward was developed through reallocation of resources from within the
      hospital to the short stay ward. This resulted in estimated savings of $1/2
      million (Westmead Hospital) to $2.3 million (New Children's Hospital) to the
      hospital, due to more efficient bed usage. CONCLUSION: This data demonstrates the
      robust nature of the short stay ward. At these two very different institutions we
      have shown improved bed efficient and patient care in a cost-effective way. We
      have also reported on greater parental satisfaction and early return of the child
      with their family to the community.

PMID- 10966338
TI  - Uses and complications of central venous catheters inserted in a pediatric
      emergency department.
AB  - OBJECTIVE: To describe the incidence, indications, insertion sites, duration, and
      complications of central venous catheter (CVC) insertion in patients in a
      pediatric emergency department (ED). METHODS:  DESIGN: Retrospective chart
      review. SETTING: ED of an urban pediatric teaching hospital. SUBJECTS: Patients
      who had a CVC inserted in the ED from January 1992 to July 1997. RESULTS: During
      the 5.5-year study period, 121 patients were identified. Indications for
      insertion were cardiac/respiratory arrest in 20 patients (17%), lack of
      peripheral vascular access in 78 (64%), and inadequate peripheral vascular access
      in 23 (19%). Presenting diagnoses included cardiac/respiratory arrest (20),
      dehydration (19), lower respiratory tract disease (15), seizure (15), sepsis
      (13), trauma (10), and other (29). Prior to the CVC insertion, 80 (66%) patients
      had no venous access, 28 (23%) had a peripheral intravenous catheter, and 13
      (11%) had an intraosseous needle. One hundred one (83%) CVCs were inserted into
      the femoral vein, 12 (10%) into the subclavian, 7 (6%) into the internal jugular,
      and 1 (1%) into an axillary vein. There were four reported complications
      requiring the CVC to be removed, and all occurred with femoral line placement.
      There were no long-term sequelae or life-threatening or limb-threatening
      complications (95% CI = 0-2.5%). CONCLUSIONS: Central venous catheterization,
      particularly using the femoral approach, appears to a safe method of obtaining
      central venous access in the critically ill infant, child, or young adult.

PMID- 10966339
TI  - Appendiceal perforation in children diagnosed in a pediatric emergency
      department.
AB  - OBJECTIVE: To determine the incidence of appendiceal perforation (AP) among
      children with acute appendicitis (AA) and determine factors associated with AP.
      DESIGN: Retrospective chart review. SETTING: Emergency department (ED) of Primary
      Children's Medical Center (PCMC). PATIENTS: 131 children less than 17 years of
      age with AA diagnosed in the PCMC ED. RESULTS: The overall rate of AP was 47%.
      One hundred eleven (85%) children with AA were correctly diagnosed on their first
      ED visit. Patients with AP had a significantly (P < 0.05) lower median age (8.0
      vs 11.0 years), longer duration of illness (3.0 vs 1.4 days), greater incidence
      of vomiting and fever by history (91% vs 69% and 83% vs 58%, respectively),
      higher median temperatures (39.0 degrees vs 38.3 degrees C), and higher
      proportions of leukocyte (WBC) band forms (14% vs 5%). Patients with AP did not
      differ from those without AP with respect to total WBC count, hour of arrival, or
      number of ED visits. CONCLUSIONS: The rate of AP among pediatric patients with AA
      is greater among younger children and is associated with vomiting, prolonged
      illness, and higher body temperatures. Unexpectedly, patients with AP did not
      have higher total WBC values, more frequent late night arrivals, a longer time
      interval prior to surgery, or more ED visits prior to diagnosis. These findings
      suggest that efforts to decrease the rate of AP should be directed toward
      heightening awareness among primary care physicians regarding the high rate of AP
      in children, with an emphasis on early ED and surgical referral.

PMID- 10966340
TI  - Accidental isopropanol ingestion in children.
AB  - OBJECTIVE: To describe the clinical course and determine the minimal observation
      period required following isopropanol ingestion in children. METHODS: The
      emergency department records of children less than 6 years of age with
      isopropanol ingestion who presented between June 1992 and December 1998 were
      identified. Demographics, type, and amount of ingested substance, and time of
      ingestion were recorded. Symptoms, time of onset, and the results of physical
      examination and laboratory tests were collected. Group 1 included patients who
      did not have isopropanol level assayed, and group 2 members had isopropanol level
      assayed. RESULTS: Ninety-one cases of isopropanol ingestion were identified.
      Clinical evidence of toxicity was noted in 26 (29%) patients. Symptoms included
      spontaneous emesis in (24/26), ataxia (5/26), altered mental status (3/26), and
      apnea (1/26). Toxic isopropanol levels were noted in three patients; all had
      altered mental status. Clinical evidence of toxicity developed between 0.5 and 2
      hours post-ingestion. Patients who ingested more than 1 ounce of isopropanol were
      more likely to become symptomatic (RR 4.26, 95% CI = 1.61-11.2). CONCLUSIONS: An
      observation period of 2 hours post-ingestion can be used to rule out clinical
      toxicity in pediatric patients with suspected isopropanol ingestion. Patients
      with a history of ingesting more than 1 ounce are likely to develop adverse
      clinical effects. The development of altered mental status is the most useful
      clinical predictor of a toxic blood isopropanol level.

PMID- 10966341
TI  - Use of CT scan in the diagnosis of pediatric acute appendicitis.
AB  - BACKGROUND: The efficacy of CT scan in the diagnosis of pediatric appendicitis
      has hot been established. METHODS: Every patient under the age of 18 who was
      diagnosed and treated for acute appendicitis in the 1 year period from March 1998
      March 1999 at Lakeland Regional Medical Center were included. The presentation,
      laboratory evaluation, imaging evaluation, hospital course, and pathologic
      evaluation were reviewed. Selected imaging studies were reviewed by an
      independent radiologist. RESULTS: Forty-six patients were treated for
      appendicitis; 17 of them received CT scans (37%). The CT scans predicted
      appendicitis in 9 of 17 cases (sensitivity = 53%). False-negative studies
      resulted in some morbidity but no mortality. The radiology review indicated that
      three cases clearly did not demonstrate appendicitis. The other false-negative
      studies were secondary to either technical or professional factors. CONCLUSION:
      The efficacy of CT imaging in the diagnosis of acute appendicitis in children has
      still not been demonstrated. This limited series indicates that if CT scanning is
      to be used in pediatric patients, more attention to technical and professional
      factors may be required. Some of these factors, particularly the ingestion of
      oral contrast, are particularly problematic in small children and may limit the
      effectiveness of this modality.

PMID- 10966342
TI  - Acute traumatic compartment syndrome of the foot in children.
AB  - Acute traumatic compartment syndrome of the foot is a sequelae of serious injury
      to the foot, which, if unrecognized, may result in significant motor and sensory
      deficits, pain, stiffness, and deformity. It is nearly always associated with
      fractures, dislocations, and crush injuries to the foot. Vascular injuries and
      coagulopathic states are also risk factors for the development of an acute foot
      compartment syndrome. In children, the presentation of an acute foot compartment
      syndrome may be masked by the pain and edema caused by associated fractures and
      dislocations. A high index of suspicion is warranted in children presenting with
      foot injuries that are associated with foot compartment syndrome. Recognition of
      the signs and symptoms of compartment syndrome in the emergency room are
      paramount; the diagnosis is best confirmed by multiple compartment pressure
      readings. The urgency of diagnosis of a compartment syndrome must be underscored,
      as the complications of a missed foot compartment syndrome includes contractures,
      claw toe deformity, sensory loss, stiffness, and chronic pain. Prompt orthopaedic
      consultation is mandatory; urgent compartment fasciotomies are associated with a
      good clinical outcome.

PMID- 10966343
TI  - Candidal arthritis in infants previously treated for systemic candidiasis during
      the newborn period: report of three cases.

PMID- 10966344
TI  - CNS toxicity after topical application of EMLA cream on a toddler with molluscum
      contagiosum.
AB  - EMLA (eutectic mixture of local anesthetics) cream is used topically to provide
      local anesthesia for a variety of painful superficial procedures. Although the
      side effects of EMLA are usually mild and transient local skin reactions,
      potential life threatening complications can be encountered. We report a case of
      central nervous toxicity after EMLA application for curettage of molluscum
      contagiosum lesions in a pediatric patient. This complication was the result of a
      therapeutic misadventure that led to an excessive application of EMLA cream over
      an extensive area causing an overdose of lidocaine and prilocaine with their
      subsequent systemic toxicities.

PMID- 10966345
TI  - Tuberous sclerosis presenting with bowel obstruction and an aortic aneurysm.

PMID- 10966346
TI  - Galeazzi fracture resulting from electrical shock.
AB  - Electrical injuries may cause tetanic contractions capable of producing
      fractures, even at very low voltages. Patients with localized pain and swelling
      require radiographs to assess for fracture, even in the absence of other
      associated trauma.

PMID- 10966347
TI  - Hemorrhagic shock and encephalopathy syndrome: neurologic features.
AB  - Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe disease that
      affects previously healthy infants of less than 1 year of age and is associated
      with significant mortality and neurologic morbidity. It is characterized by
      sudden onset of shock, convulsions and coma, bleeding due to severe coagulopathy,
      fever, diarrhea, metabolic acidosis, and hepatorenal dysfunction. Central nervous
      system involvement with recurrent seizures and brain edema is the most common
      cause of high mortality and neurological morbidity. In this report, we describe
      four patients of HSES and review the initial and follow-up neurological features,
      electroencephalography findings, and the results of neuroradiological
      examinations of this catastrophic illness.

PMID- 10966349
TI  - "Tail of newt": an unusual ingestion.

PMID- 10966348
TI  - A case report: type I choledochal cyst induced pancreatitis in a 15-month-old
      child.

PMID- 10966350
TI  - Penetrating neck trauma: an unusual presentation.

PMID- 10966351
TI  - Integration of foreign and local medical staff in a disaster area: the La Ceiba,
      Honduras experience.

PMID- 10966352
TI  - Sports-related concussions.
AB  - Concussion is the most common head injury occurring in sports participation.
      Concussions range from a brief period of neural dysfunction to a prolonged period
      of unconsciousness with retrograde amnesia. It is imperative that the pediatric
      emergency medicine specialist be familiar with the proper initial assessment of
      the child or adolescent athlete who has sustained a sports-related concussion,
      the latest grading scales of concussions, and the current recommendations for
      returning the athlete to competition. A systematic approach to the athlete who
      has suffered a concussion will minimize the risk of further injury or mortality.

PMID- 10966353
TI  - Swollen and painful left testicle.

PMID- 10966354
TI  - Exhaled nitric oxide as an indicator of severity of asthmatic inflammation.
AB  - Traditional assessment of severity of asthma relies on an evaluation of signs and
      symptoms and pulmonary function tests. These pulmonary function tests, such as
      peak expiratory flow rates, forced vital capacity, and forced expiratory flow
      rates, are indirect measures of airway caliber only, and not inflammation. Since
      asthma is an inflammatory disease, a measure of the degree of inflammation would
      be helpful in quantitating severity and titrating of anti-inflammatory therapy. A
      noninvasive method for measuring pulmonary inflammation would therefore be
      helpful to assist the emergency physician in initial treatment and assist in
      titration of anti-inflammatory therapy during repeat visits. Exhaled nitric oxide
      (NO) assays are convenient and practical and may fulfill this role. In this
      review, we discuss the role of NO in asthmatic inflammation and the role that
      exhaled NO values may play in the emergency management of asthma.

PMID- 10966355
TI  - The role of intravenous valproic acid in status epilepticus.
AB  - Valproic acid (VA) has been reported to be effective in status epilepticus (SE)
      when given rectally. More recently, intravenous (IV) VA has been demonstrated to
      be effective and safe. Pharmacokinetic studies and initial clinical experience
      with IV valproic acid suggest that it may have a useful role in the management of
      refractory status epilepticus, but the magnitude of its utility is not possible
      to quantify or compare with phenytoin and phenobarbital. In simple SE, IV VA
      provides less additional benefit, since standard therapy usually works well. IV
      VA may be useful as a substitute for standard simple SE therapy, but this is
      difficult to justify unless adverse reactions to standard therapy are
      anticipated. The published pediatric experience with IV VA for SE is scant.

PMID- 10966356
TI  - Pharmacology in the mild head trauma patient.

PMID- 10966357
TI  - Pediatric emergency medicine: legal briefs.

PMID- 10966358
TI  - Nasal wash technique for nasal foreign body removal.

PMID- 10966359
TI  - Fairy dust.

PMID- 10966361
TI  - Tibiocalcaneal arthrodesis for the management of severe ankle and hindfoot
      deformities.
AB  - PURPOSE: The purpose of this investigation was to evaluate the outcome of
      tibiocalcaneal arthrodesis using an adolescent condylar blade plate for severe
      ankle and hindfoot deformities. MATERIALS AND METHODS: We retrospectively
      reviewed the records of patients managed at our institutions between 1989 and
      1996 whose tibiocalcaneal arthrodeses were performed with adolescent condylar
      blade plates and allograft bone. In these 30 patients (14 men, 16 women; average
      age, 53 years), the etiologies of the nonbraceable deformity included: diabetic
      neuroarthropathy with talar fragmentation and resorption (26), inflammatory
      arthritis (3), and posttraumatic avascular necrosis of the talus with collapse
      (1). Due to the severity of the deformity in 28 of these patients, the
      alternative treatment would have been amputation. Thirteen patients had undergone
      previous surgeries, eight had documented osteomyelitis, and 13 had ulcers ranging
      from 2 to 27 mm. At surgery, the remnants of the talus were removed. Morcellized
      bone graft mixed with tobramycin/vancomycin powder was inserted into the
      arthrodesis site and then fixed with a rigid plate. Intravenous antibiotics,
      followed by oral antibiotics, were given until wound healing and suture removal.
      Follow-up averaged 48 months (19 to 112 months). RESULTS: Tibiocalcaneal fusion
      was achieved in 28/30 patients at an average of 16 weeks (12 to 18 weeks).
      Complications occurred in seven patients: two developed stress fractures of the
      tibia at the proximal end of the blade plate, three had superficial cellulitis
      that resolved with antibiotic therapy, and two had nonunions. CONCLUSION:
      Tibiocalcaneal arthrodesis using an adolescent condylar blade plate and allograft
      bone can be a successful procedure in the patient with severe neuropathic ankle
      deformity and can achieve a stable plantigrade foot for limited community
      ambulation with relatively few complications.

PMID- 10966360
TI  - Comparison of results of retrocalcaneal decompression for retrocalcaneal bursitis
      and insertional achilles tendinosis with calcific spur.
AB  - Sixteen feet with retrocalcaneal bursitis (RB) and twenty-two feet with calcific
      Achilles insertional tendinosis (IAT-CS) underwent retrocalcaneal decompression
      after failure of nonoperative treatment. Follow-up evaluation at least two years
      after surgery included AOFAS Ankle-Hindfoot subscale scores, satisfaction, time
      until maximum symptomatic improvement, and radiographs. Statistically significant
      differences between the groups include the following: IAT-CS patients were older,
      required nearly twice the time to reach maximum symptomatic improvement, had
      lower satisfaction rates, had a lower pain score, and more frequently had
      shoewear restrictions. Radiographic recurrence did not correlate with outcome or
      symptomatic recurrence.

PMID- 10966362
TI  - Precise anatomic configuration changes in the first ray of the hallux valgus
      foot.
AB  - To detect precise anatomical configuration of the first ray in feet with hallux
      valgus, a two-dimensional coordinate system was devised for evaluation of a
      weight-bearing dorsoplantar radiograph. The radiographs, taken from 229 feet of
      114 patients with symptomatic hallux valgus and 94 normal feet, were
      investigated. A comparative study showed the first metatarsal head of a foot with
      hallux valgus was located on the medial side of that of the normal foot and the
      base of the proximal phalanx of the hallux valgus foot was located on the same
      point of that of the normal foot. Lateral translation of the base of the proximal
      phalanx occurred only in cases with overlap toes. Our study shows that
      subluxation of the metatarsophalangeal joint in hallux valgus is primarily caused
      by metatarsus primus varus. This study indicated that first metatarsal
      osteotomies should be given the first priority in consideration for bunion
      surgery, because these procedures could move the first metatarsal heads laterally
      in a more normal position.

PMID- 10966363
TI  - The relationship between chronic ankle instability and variations in mortise
      anatomy and impingement spurs.
AB  - Thirty-five patients undergoing a Brostrom procedure for ankle instability were
      studied retrospectively as to the presence or absence of spurs and loose bodies,
      outcome, and mortise relationships. 100 adult volunteers had their ankles
      radiographically and clinically examined for spurs, loose bodies, and laxity. 100
      patients' ankles with computed axial tomography were examined to define malleolar
      relationships. The AOFAS Hindfoot scores on the Brostrom patients with or without
      spurs were not different. Patients undergoing a Brostrom procedure had a 3.37
      times incidence of spurs and/or loose bodies compared to normal adult population.
      The incidence of asymmetric but asymptomatic ankle laxity in normal adults was
      11%. The fibula has a 38 degree range of position relative to the axis of the
      talus and the medial malleolus. A posterior fibular position may predispose to
      injury.

PMID- 10966364
TI  - Congruity of the subtalar joint in tongue fracture of the calcaneus: an
      anatomical study.
AB  - STUDY DESIGN: An anatomic study. OBJECTIVES: To evaluate the effect of
      displacement of the fractured posterior facet in tongue fracture of the calcaneus
      on the congruity of the subtalar joint. METHODS: Eleven feet were used in this
      study. Seven females and four males with age range from 59 to 78. The specimens
      were dissected from both the lateral and the medial aspects of the calcaneus to
      expose these surfaces. A primary fracture line was created first, then a
      secondary line was engineered to simulate tongue fracture. Displacement of the
      superio-lateral fragment was done with 5-mm increment. Radiography was performed
      and the graphs were scanned and studied on specific computer software to explore
      the effects of displacement on joint congruity. RESULTS: The anterior end of the
      fragment of the tongue fracture, when displaced, not only is depressed but also
      rotated in the sagittal plane in a downward or planterward direction. The
      articular surface of the posterior facet of the calcaneus and the inferior facet
      of the talus are maintained in congruence with each other despite the varying
      degree of displacement and rotation. CONCLUSION: Congruity of the subtalar joint
      in tongue fractures is maintained despite different degrees of displacement. This
      study explains why the non-surgical treatment outcome is comparable to that of
      the operative treatment in tongue fractures of calcaneus. It also explains why
      tongue fractures have a good outcome with closed reduction.

PMID- 10966365
TI  - Tarsal coalition in adults.
AB  - 32 feet in 27 adults, seen at The Johns Hopkins Hospital Foot and Ankle Clinic
      from 1993-1998, with the diagnosis of tarsal coalition were retrospectively
      reviewed. There were 18 subtalar coalitions, 14 calcaneonavicular coalitions and
      1 naviculocuneiform coalition. The average age was 40 years. Clinically, 22 feet
      had a neutral heel, 7 had a valgus heel with flattening of the longitudinal arch,
      1 had a varus heel and 2 heels had an unknown position. Subtalar motion was
      decreased in 23 feet. Peroneal spasm was only seen in 2 patients. 11 feet were
      asymptomatic. Nonoperative treatment consisting of activity modification,
      nonsteroidal anti-inflammatory medications and casting was successful in the
      majority of patients. Subtalar fusion was performed in 4 feet and coalition
      resection in 1. The treatment of a symptomatic tarsal coalition in the adult is
      as in children but the clinical presentation may differ.

PMID- 10966366
TI  - Should the amputations of the great toe be replanted?
AB  - Seventeen great toes, amputated at the distal phalangeal to the level of the MTP
      joint, were replanted between 1990 and 1998, at Izmir Hand and Microsurgery
      Hospital. Replantation in five out of six complete amputations, and seven out of
      eleven incomplete amputations were successful, and the overall survival rate was
      76.4%. In failed replantations, the base of the proximal phalanx of the great toe
      was preserved during closing of the stump. Nine of 17 patients were available for
      review in the follow-up period of mean 3.5 years (range 1-6.5 years). Clinical
      and biomechanical evaluations of the operated feet were carried out in five
      patients who had replanted great toe, and in four patients who had amputated one.
      The uninjured sides were used as control group. The patients in the two groups
      had no significant subjective symptoms, nearly normal ROM of the MTP joint and
      protective sensation was achieved in the replanted great toes. With the numbers
      available, while radiographical parameters of the involved and the control sides
      demonstrated no significant differences in either groups, pedographical studies
      revealed consistent changes in weight-bearing distribution of the feet with
      amputated great toes. Although the great toe amputation causes no disturbance in
      gait, it alters the load distribution of the foot.

PMID- 10966367
TI  - Acute compartment syndrome following revisional arthroplasty of the forefoot: the
      dangers of ankle-block.
AB  - A case of acute compartment syndrome of the forefoot after revisional
      arthroplasty of the forefoot is presented. Shortening of the compartments due to
      bony resection and extensive dissection due to previous scarring may have
      predisposed to the pathological condition. Prompt decompression based on clinical
      grounds prevented any long term sequelae. Allowance must be made for the
      concomitant use of local anaesthetic procedures which may obscure the clinical
      picture.

PMID- 10966368
TI  - Retrograde intramedullary nail for metastatic lesion of the lower tibia.
AB  - Two cases of distal tibial metastases are presented, and a suggestion is made for
      a method of treatment.

PMID- 10966369
TI  - Pressure controlled Esmarch bandage used as a tourniquet.
AB  - The objective of this paper is to investigate the manual wrapping techniques of
      Esmarch bandages used as tourniquets by physicians and to study the
      controllability of their induced pressure. The properties of the Esmarch bandage
      were first tested using two cylinders to allow uniform stretching of the bandage
      and to control the elastic exercusion and pressure reading. The pressure was
      measured using a load cell and a DPSI electronic strain/stress/pressure indicator
      device. The placement of the load cell sensor was found to yield constant values
      when measured along the lateral direction normal to the tension directional field
      of the cylinder. The results also show that the pressure increases at a rate 3 to
      4 times the initial pressure when the bandage is stretched after each wrap rather
      than over the total length initially. The measurements over a plaster foot showed
      different pressure readings but exhibited a linear relationship in all three
      wraps performed. The method also shows a linear relationship between the elastic
      deformation and the number of wraps necessary to achieve a certain degree of
      mmHg.

PMID- 10966370
TI  - Fracture of an interphalangeal coalition: a report of two cases.
AB  - Congenital coalition of the middle and distal phalanges in the fifth toe are
      common. They have been reported to occur in up to 50% of American and European
      populations and in up to 73% of people of Japanese descent. Congenital
      interphalangeal coalition of the other toes is less common. We report two cases
      of fracture through an interphalangeal coalition following blunt trauma.
      Diagnosis was delayed in these fractures. One fracture healed only after
      prolonged immobilization and the other developed a delayed union. Patients with
      this fracture should be advised of the prolonged convalescence since this may
      delay their return to preinjury activities.

PMID- 10966371
TI  - A review of tendon passing techniques and introduction of a new method using a
      suction tip.

PMID- 10966372
TI  - Spontaneous rupture of the tibialis anterior tendon: a case report and literature
      review.
AB  - Spontaneous rupture of the tibialis anterior tendon is uncommon. This article
      presents a case report in which spontaneous rupture of the tibialis anterior
      tendon occurred secondary to a gouty tophaceous deposit within the tendon. This
      report adds to the list of pathological conditions that should be considered in
      closed spontaneous rupture of the tibialis anterior tendon.

PMID- 10966373
TI  - The bacterium's way for safe enlargement and division.

PMID- 10966374
TI  - Microbial community dynamics during production of the Mexican fermented maize
      dough pozol.
AB  - The dynamics of the microbial community responsible for the traditional
      fermentation of maize in the production of Mexican pozol was investigated by
      using a polyphasic approach combining (i) microbial enumerations with culture
      media, (ii) denaturing gradient gel electrophoresis (DGGE) fingerprinting of
      total community DNA with bacterial and eukaryotic primers and sequencing of
      partial 16S ribosomal DNA (rDNA) genes, (iii) quantification of rRNAs from
      dominant microbial taxa by using phylogenetic oligonucleotide probes, and (iv)
      analysis of sugars and fermentation products. A Streptococcus species dominated
      the fermentation and accounted for between 25 and 75% of the total flora
      throughout the process. Results also showed that the initial epiphytic aerobic
      microflora was replaced in the first 2 days by heterofermentative lactic acid
      bacteria (LAB), including a close relative of Lactobacillus fermentum, producing
      lactic acid and ethanol; this heterolactic flora was then progressively replaced
      by homofermentative LAB (mainly close relatives of L. plantarum, L. casei, and L.
      delbrueckii) which continued acidification of the maize dough. At the same time,
      a very diverse community of yeasts and fungi developed, mainly at the periphery
      of the dough. The analysis of the DGGE patterns obtained with bacterial and
      eukaryotic primers targeting the 16S and 18S rDNA genes clearly demonstrated that
      there was a major shift in the community structure after 24 h and that high
      biodiversity-according to the Shannon-Weaver index-was maintained throughout the
      process. These results proved that a relatively high number of species, at least
      six to eight, are needed to perform this traditional lactic acid fermentation.
      The presence of Bifidobacterium, Enterococcus, and enterobacteria suggests a
      fecal origin of some important pozol microorganisms. Overall, the results
      obtained with different culture-dependent or -independent techniques clearly
      confirmed the importance of developing a polyphasic approach to study the ecology
      of fermented foods.

PMID- 10966375
TI  - Response of atmospheric methane consumption by maine forest soils to exogenous
      aluminum salts.
AB  - Atmospheric methane consumption by Maine forest soils was inhibited by additions
      of environmentally relevant levels of aluminum. Aluminum chloride was more
      inhibitory than nitrate or sulfate salts, but its effect was comparable to that
      of a chelated form of aluminum. Inhibition could be explained in part by the
      lower soil pH values which resulted from aluminum addition. However,
      significantly greater inhibition by aluminum than by mineral acids at equivalent
      soil pH values indicated that inhibition also resulted from direct effects of
      aluminum per se. The extent of inhibition by exogenous aluminum increased with
      increasing methane concentration for soils incubated in vitro. At methane
      concentrations of >10 ppm, inhibition could be observed when aluminum chloride
      was added at concentrations as low as 10 nmol g (fresh weight) of soil(-1). These
      results suggest that widespread acidification of soils and aluminum mobilization
      due to acid precipitation may exacerbate inhibition of atmospheric methane
      consumption due to changes in other parameters and increase the contribution of
      methane to global warming.

PMID- 10966376
TI  - Physiological and chemical investigations into microbial degradation of synthetic
      Poly(cis-1,4-isoprene).
AB  - Streptomyces coelicolor 1A and Pseudomonas citronellolis were able to degrade
      synthetic high-molecular-weight poly(cis-1,4-isoprene) and vulcanized natural
      rubber. Growth on the polymers was poor but significantly greater than that of
      the nondegrading strain Streptomyces lividans 1326 (control). Measurement of the
      molecular weight distribution of the polymer before and after degradation showed
      a time-dependent increase in low-molecular-weight polymer molecules for S.
      coelicolor 1A and P. citronellolis, whereas the molecular weight distribution for
      the control (S. lividans 1326) remained almost constant. Three degradation
      products were isolated from the culture fluid of S. coelicolor 1A grown on
      vulcanized rubber and were identified as (6Z)-2,6-dimethyl-10-oxo-undec-6-enoic
      acid, (5Z)-6-methyl-undec-5-ene-2,9-dione, and (5Z,9Z)-6, 10-dimethyl-pentadec
      5,9-diene-2,13-dione. An oxidative pathway from poly(cis-1,4-isoprene) to methyl
      branched diketones is proposed. It includes (i) oxidation of an aldehyde
      intermediate to a carboxylic acid, (ii) one cycle of beta-oxidation, (iii)
      oxidation of the conjugated double bond resulting in a beta-keto acid, and (iv)
      decarboxylation.

PMID- 10966378
TI  - Quantitative approach in the study of adhesion of lactic acid bacteria to
      intestinal cells and their competition with enterobacteria.
AB  - To describe the phenomena of bacterial adhesion to intestinal cells and the
      competition for adhesion between bacteria, mathematical equations based on a
      simple dissociation process involving a finite number of bacterial receptors on
      intestinal cell surface were developed. The equations allow the estimation of the
      maximum number of Lactobacillus sp. and Escherichia coli cells that can adhere to
      Caco-2 cells and intestinal mucus; they also characterize the affinity of the
      bacteria to Caco-2 cells and intestinal and fecal mucus and the theoretical
      adhesion ratio of two bacteria present in a mixed suspension. The competition for
      adhesion between Lactobacillus rhamnosus GG and E. coli TG1 appeared to follow
      the proposed kinetics, whereas the competition between Lactobacillus casei
      Shirota and E. coli TG1 may involve multiple adhesion sites or a soluble factor
      in the culture medium of the former. The displacement of the adhered
      Lactobacillus by E. coli TG1 seemed to be a rapid process, whereas the
      displacement of E. coli TG1 by the Lactobacillus took more than an hour.

PMID- 10966377
TI  - Changes in glycolytic activity of Lactococcus lactis induced by low temperature.
AB  - The effects of low-temperature stress on the glycolytic activity of the lactic
      acid bacterium Lactococcus lactis were studied. The maximal glycolytic activity
      measured at 30 degrees C increased approximately 2.5-fold following a shift from
      30 to 10 degrees C for 4 h in a process that required protein synthesis. Analysis
      of cold adaptation of strains with genes involved in sugar metabolism disrupted
      showed that both the phosphoenolpyruvate-dependent sugar phosphotransferase
      system (PTS) subunit HPr and catabolite control protein A (CcpA) are involved in
      the increased acidification at low temperatures. In contrast, a strain with the
      PTS subunit enzyme I disrupted showed increased acidification similar to that in
      the wild-type strain. This indicates that the PTS is not involved in this
      response whereas the regulatory function of 46-seryl phosphorylated HPr [HPr(Ser
      P)] probably is involved. Protein analysis showed that the production of both HPr
      and CcpA was induced severalfold (up to two- to threefold) upon exposure to low
      temperatures. The las operon, which is subject to catabolite activation by the
      CcpA-HPr(Ser-P) complex, was not induced upon cold shock, and no increased
      lactate dehydrogenase (LDH) activity was observed. Similarly, the rate-limiting
      enzyme of the glycolytic pathway under starvation conditions, glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), was not induced upon cold shock. This indicates
      that a factor other than LDH or GAPDH is rate determining for the increased
      glycolytic activity upon exposure to low temperatures. Based on their cold
      induction and involvement in cold adaptation of glycolysis, it is proposed that
      the CcpA-HPr(Ser-P) control circuit regulates this factor(s) and hence couples
      catabolite repression and cold shock response in a functional and mechanistic
      way.

PMID- 10966379
TI  - Classification of antibiotic resistance patterns of indicator bacteria by
      discriminant analysis: use in predicting the source of fecal contamination in
      subtropical waters.
AB  - The antibiotic resistance patterns of fecal streptococci and fecal coliforms
      isolated from domestic wastewater and animal feces were determined using a
      battery of antibiotics (amoxicillin, ampicillin, cephalothin, chlortetracycline,
      oxytetracycline, tetracycline, erythromycin, streptomycin, and vancomycin) at
      four concentrations each. The sources of animal feces included wild birds,
      cattle, chickens, dogs, pigs, and raccoons. Antibiotic resistance patterns of
      fecal streptococci and fecal coliforms from known sources were grouped into two
      separate databases, and discriminant analysis of these patterns was used to
      establish the relationship between the antibiotic resistance patterns and the
      bacterial source. The fecal streptococcus and fecal coliform databases classified
      isolates from known sources with similar accuracies. The average rate of correct
      classification for the fecal streptococcus database was 62.3%, and that for the
      fecal coliform database was 63.9%. The sources of fecal streptococci and fecal
      coliforms isolated from surface waters were identified by discriminant analysis
      of their antibiotic resistance patterns. Both databases identified the source of
      indicator bacteria isolated from surface waters directly impacted by septic tank
      discharges as human. At sample sites selected for relatively low anthropogenic
      impact, the dominant sources of indicator bacteria were identified as various
      animals. The antibiotic resistance analysis technique promises to be a useful
      tool in assessing sources of fecal contamination in subtropical waters, such as
      those in Florida.

PMID- 10966380
TI  - Role of phaD in accumulation of medium-chain-length Poly(3-hydroxyalkanoates) in
      Pseudomonas oleovorans.
AB  - Pseudomonas oleovorans is capable of producing poly(3-hydroxyalkanoates) (PHAs)
      as intracellular storage material. To analyze the possible involvement of phaD in
      medium-chain-length (MCL) PHA biosynthesis, we generated a phaD knockout mutant
      by homologous recombination. Upon disruption of the phaD gene, MCL PHA polymer
      accumulation was decreased. The PHA granule size was reduced, and the number of
      granules inside the cell was increased. Furthermore, mutant cells appeared to be
      smaller than wild-type cells. Investigation of MCL PHA granules revealed that the
      pattern of granule-associated proteins was changed and that the predominant
      protein PhaI was missing in the mutant. Complementation of the mutant with a phaD
      harboring plasmid partially restored the wild-type characteristics of MCL PHA
      production and fully restored the granule and cell sizes. Furthermore, PhaI was
      attached to the granules of the complemented mutant. These results indicate that
      the phaD gene encodes a protein which plays an important role in MCL PHA
      biosynthesis. However, although its main effect seems to be the stabilization of
      MCL PHA granules, we found that the PhaD protein is not a major granule
      associated protein and therefore might act by an unknown mechanism involving the
      PhaI protein.

PMID- 10966381
TI  - Modeling reduction of uranium U(VI) under variable sulfate concentrations by
      sulfate-reducing bacteria.
AB  - The kinetics for the reduction of sulfate alone and for concurrent uranium
      [U(VI)] and sulfate reduction, by mixed and pure cultures of sulfate-reducing
      bacteria (SRB) at 21 +/- 3 degrees C were studied. The mixed culture contained
      the SRB Desulfovibrio vulgaris along with a Clostridium sp. determined via 16S
      ribosomal DNA analysis. The pure culture was Desulfovibrio desulfuricans (ATCC
      7757). A zero-order model best fit the data for the reduction of sulfate from 0.1
      to 10 mM. A lag time occurred below cell concentrations of 0.1 mg (dry weight) of
      cells/ml. For the mixed culture, average values for the maximum specific reaction
      rate, V(max), ranged from 2.4 +/- 0.2 micromol of sulfate/mg (dry weight) of SRB.
      h(-1)) at 0.25 mM sulfate to 5.0 +/- 1.1 micromol of sulfate/mg (dry weight) of
      SRB. h(-1) at 10 mM sulfate (average cell concentration, 0.52 mg [dry
      weight]/ml). For the pure culture, V(max) was 1.6 +/- 0.2 micromol of sulfate/mg
      (dry weight) of SRB. h(-1) at 1 mM sulfate (0.29 mg [dry weight] of cells/ml).
      When both electron acceptors were present, sulfate reduction remained zero order
      for both cultures, while uranium reduction was first order, with rate constants
      of 0.071 +/- 0.003 mg (dry weight) of cells/ml. min(-1) for the mixed culture and
      0.137 +/- 0.016 mg (dry weight) of cells/ml. min(-1) (U(0) = 1 mM) for the D.
      desulfuricans culture. Both cultures exhibited a faster rate of uranium reduction
      in the presence of sulfate and no lag time until the onset of U reduction in
      contrast to U alone. This kinetics information can be used to design an SRB
      dominated biotreatment scheme for the removal of U(VI) from an aqueous source.

PMID- 10966382
TI  - Spatial patterns in antibiotic resistance among stream bacteria: effects of
      industrial pollution.
AB  - The spatial distribution of antibiotic resistance to streptomycin and kanamycin
      was examined in natural bacterial communities of two streams. The proportion of
      resistant bacteria was substantially higher (P < 0.05) in the midreaches of an
      industrially perturbed stream, but no such pattern was apparent in an undisturbed
      reference stream. The highest relative frequency of resistance was found at the
      confluence of a tributary draining a nuclear reactor and industrial complex.
      Antibiotic resistance increased with distance upstream from the confluence and
      was positively correlated (r(2) = 0. 54, P = 0.023) with mercury concentrations
      in the sediments. When the data for two years were compared, this pattern was
      stable for streptomycin resistance (paired t test, P < 0.05) but not for
      kanamycin resistance (P > 0.05). Our results imply that heavy metal pollution may
      contribute to increased antibiotic resistance through indirect selection.

PMID- 10966383
TI  - Thermostable chitosanase from Bacillus sp. Strain CK4: cloning and expression of
      the gene and characterization of the enzyme.
AB  - A thermostable chitosanase gene from the environmental isolate Bacillus sp.
      strain CK4, which was identified on the basis of phylogenetic analysis of the 16S
      rRNA gene sequence and phenotypic analysis, was cloned, and its complete DNA
      sequence was determined. The thermostable chitosanase gene was composed of an 822
      bp open reading frame which encodes a protein of 242 amino acids and a signal
      peptide corresponding to a 30-kDa enzyme. The deduced amino acid sequence of the
      chitosanase from Bacillus sp. strain CK4 exhibits 76.6, 15.3, and 14.2%
      similarities to those from Bacillus subtilis, Bacillus ehemensis, and Bacillus
      circulans, respectively. C-terminal homology analysis shows that Bacillus sp.
      strain CK4 belongs to cluster III with B. subtilis. The gene was similar in size
      to that of the mesophile B. subtilis but showed a higher preference for codons
      ending in G or C. The enzyme contains 2 additional cysteine residues at positions
      49 and 211. The recombinant chitosanase has been purified to homogeneity by using
      only two steps with column chromatography. The half-life of the enzyme was 90 min
      at 80 degrees C, which indicates its usefulness for industrial applications. The
      enzyme had a useful reactivity and a high specific activity for producing
      functional oligosaccharides as well, with trimers through hexamers as the major
      products.

PMID- 10966384
TI  - Germination-induced bioluminescence, a route to determine the inhibitory effect
      of a combination preservation treatment on bacterial spores.
AB  - In this work, we have used spores of Bacillus subtilis that specifically induce
      bioluminescence upon initiation of germination as a rapid, real-time monitor of
      the effects of preservative treatments on germination. Using this tool, we have
      demonstrated that the combination of mild acidity (pH 5.5 to 5.0), lactic acid
      (0. 5%), and a pasteurization step (90 degrees C for 5 min) results in enhanced
      inhibition of spore germination compared with the effects of the individual
      treatments alone. Inhibition by the combination treatment occurred as a result of
      both direct but reversible inhibition, entirely dependent on the physical
      presence of the preservative factors, and permanent, nonreversible damage to the
      L-alanine germination apparatus of the spore. However, we were able to restore
      germination of the preservative-damaged spores unable to germinate on L-alanine
      by supplementing the medium with the nonnutrient germinant calcium dipicolinic
      acid. The demonstration that simple combinations of preservative factors inhibit
      spore germination indicates that food preservation systems providing ambient
      stability could be designed which do not adhere to the strict limits set by
      commonly accepted processes and which are based on precise understanding of their
      inhibitory action.

PMID- 10966385
TI  - Direct and Fe(II)-mediated reduction of technetium by Fe(III)-reducing bacteria.
AB  - The dissimilatory Fe(III)-reducing bacterium Geobacter sulfurreducens reduced and
      precipitated Tc(VII) by two mechanisms. Washed cell suspensions coupled the
      oxidation of hydrogen to enzymatic reduction of Tc(VII) to Tc(IV), leading to the
      precipitation of TcO(2) at the periphery of the cell. An indirect, Fe(II)
      mediated mechanism was also identified. Acetate, although not utilized
      efficiently as an electron donor for direct cell-mediated reduction of
      technetium, supported the reduction of Fe(III), and the Fe(II) formed was able to
      transfer electrons abiotically to Tc(VII). Tc(VII) reduction was comparatively
      inefficient via this indirect mechanism when soluble Fe(III) citrate was supplied
      to the cultures but was enhanced in the presence of solid Fe(III) oxide. The rate
      of Tc(VII) reduction was optimal, however, when Fe(III) oxide reduction was
      stimulated by the addition of the humic analog and electron shuttle anthaquinone
      2,6-disulfonate, leading to the rapid formation of the Fe(II)-bearing mineral
      magnetite. Under these conditions, Tc(VII) was reduced and precipitated
      abiotically on the nanocrystals of biogenic magnetite as TcO(2) and was removed
      from solution to concentrations below the limit of detection by scintillation
      counting. Cultures of Fe(III)-reducing bacteria enriched from radionuclide
      contaminated sediment using Fe(III) oxide as an electron acceptor in the presence
      of 25 microM Tc(VII) contained a single Geobacter sp. detected by 16S ribosomal
      DNA analysis and were also able to reduce and precipitate the radionuclide via
      biogenic magnetite. Fe(III) reduction was stimulated in aquifer material,
      resulting in the formation of Fe(II)-containing minerals that were able to reduce
      and precipitate Tc(VII). These results suggest that Fe(III)-reducing bacteria may
      play an important role in immobilizing technetium in sediments via direct and
      indirect mechanisms.

PMID- 10966386
TI  - Development of a fluorogenic 5' nuclease PCR assay for detection of the ail gene
      of pathogenic Yersinia enterocolitica.
AB  - In this report we describe the development and evaluation of a fluorogenic PCR
      assay for the detection of pathogenic Yersinia enterocolitica. The assay targets
      the chromosomally encoded attachment and invasion gene, ail. Three primer-probe
      sets (TM1, TM2, and TM3) amplifying different, yet overlapping, regions of ail
      were examined for their specificity and sensitivity. All three primer-probe sets
      were able to detect between 0.25 and 0.5 pg of purified Y. enterocolitica DNA.
      TM1 identified all 26 Y. enterocolitica strains examined. TM3 was able to detect
      all strains except one, whereas TM2 was unable to detect 10 of the Y.
      enterocolitica strains tested. None of the primer-probe sets cross-reacted with
      any of the 21 non-Y. enterocolitica strains examined. When the TM1 set was
      utilized, the fluorogenic PCR assay was able to detect </=4 Y. enterocolitica
      CFU/ml in pure culture and 10 Y. enterocolitica CFU/ml independent of the
      presence of 10(8) CFU of contaminating bacteria per ml. This set was also capable
      of detecting </=1 CFU of Y. enterocolitica per g of ground pork or feces after a
      24-h enrichment in a Yersinia selective broth.

PMID- 10966387
TI  - Physiological and regulatory effects of controlled overproduction of five cold
      shock proteins of Lactococcus lactis MG1363.
AB  - The physiological and regulatory effects of overproduction of five cold shock
      proteins (CSPs) of Lactococcus lactis were studied. CspB, CspD, and CspE could be
      overproduced at high levels (up to 19% of the total protein), whereas for CspA
      and CspC limited overproduction (0.3 to 0.5% of the total protein) was obtained.
      Northern blot analysis revealed low abundance of the cspC transcript, indicating
      that the stability of cspC mRNA is low. The limited overproduction of CspA is
      likely to be caused by low stability of CspA since when there was an Arg-Pro
      mutation at position 58, the level of CspA production increased. Using two
      dimensional gel electrophoresis, it was found that upon overproduction of the
      CSPs several proteins, including a number of cold-induced proteins of L. lactis,
      were induced. Strikingly, upon overproduction of CspC induction of CspB, putative
      CspF, and putative CspG was also observed. Overproduction of CspB and
      overproduction of CspE result in increased survival when L. lactis is frozen
      (maximum increases, 10- and 5-fold, respectively, after 4 freeze-thaw cycles). It
      is concluded that in L. lactis CSPs play a regulatory role in the cascade of
      events that are initiated by cold shock treatment and that they either have a
      direct protective effect during freezing (e.g., RNA stabilization) or induce
      other factors involved in the freeze-adaptive response or both.

PMID- 10966388
TI  - Characterization of Leuconostoc gasicomitatum sp. nov., associated with spoiled
      raw tomato-marinated broiler meat strips packaged under modified-atmosphere
      conditions.
AB  - Lactic acid bacteria (LAB) associated with gaseous spoilage of modified
      atmosphere-packaged, raw, tomato-marinated broiler meat strips were identified on
      the basis of a restriction fragment length polymorphism (RFLP) (ribotyping)
      database containing DNAs coding for 16S and 23S rRNAs (rDNAs). A mixed LAB
      population dominated by a Leuconostoc species resembling Leuconostoc gelidum
      caused the spoilage of the product. Lactobacillus sakei, Lactobacillus curvatus,
      and a gram-positive rod phenotypically similar to heterofermentative
      Lactobacillus species were the other main organisms detected. An increase in pH
      together with the extreme bulging of packages suggested a rare LAB spoilage type
      called "protein swell." This spoilage is characterized by excessive production of
      gas due to amino acid decarboxylation, and the rise in pH is attributed to the
      subsequent deamination of amino acids. Protein swell has not previously been
      associated with any kind of meat product. A polyphasic approach, including
      classical phenotyping, whole-cell protein electrophoresis, 16 and 23S rDNA RFLP,
      16S rDNA sequence analysis, and DNA-DNA reassociation analysis, was used for the
      identification of the dominant Leuconostoc species. In addition to the RFLP
      analysis, phenotyping, whole-cell protein analysis, and 16S rDNA sequence
      homology indicated that L. gelidum was most similar to the spoilage-associated
      species. The two spoilage strains studied possessed 98.8 and 99.0% 16S rDNA
      sequence homology with the L. gelidum type strain. DNA-DNA reassociation,
      however, clearly distinguished the two species. The same strains showed only 22
      and 34% hybridization with the L. gelidum type strain. These results warrant a
      separate species status, and we propose the name Leuconostoc gasicomitatum sp.
      nov. for this spoilage-associated Leuconostoc species.

PMID- 10966389
TI  - Effects of pH and energy supply on activity and amount of pyruvate formate-lyase
      in Streptococcus bovis.
AB  - The enzyme system of pyruvate formate-lyase (PFL) in Streptococcus bovis was
      investigated by isolating PFL and PFL-activating enzyme (PFL-AE) from S. bovis,
      flavodoxin from Escherichia coli, and chloroplasts from spinach. In this study,
      the PFL and PFL-AE in S. bovis were found to be similar to those in E. coli,
      suggesting that the activating mechanisms are similar. The optimal pH of S. bovis
      PFL was 7.5, which is in contrast to the optimal pH of S. bovis lactate
      dehydrogenase, which is 5.5. The apparent K(m) of S. bovis PFL was 2 mM. The
      intermediates of glycolysis, dihydroxyacetone phosphate (DHAP) and D
      glyceraldehyde-3-phosphate (GAP), were shown to inhibit PFL activity. The
      concentrations of intracellular DHAP and GAP in S. bovis ranged from 1.9 mM to
      less than 0.1 mM and from 0.6 mM to less than 0.05 mM, respectively, depending on
      the energy supply. The wide variations in DHAP and GAP levels indicated that PFL
      activity is allosterically regulated by these triose phosphates in vivo. The
      amount of PFL protein, as determined by Western blot analysis with polyclonal
      antibody, changed in parallel with the level of pfl-mRNA, responding to the
      culture conditions. These observations confirm that PFL synthesis is regulated at
      the transcriptional level and support the hypothesis that S. bovis shifts the
      fermentation pathway from acetate, formate, and ethanol production to lactate
      production when the pH is low and when excess energy is supplied.

PMID- 10966390
TI  - A serine protease-encoding gene (aprII) of Alteromonas sp. Strain O-7 is
      regulated by the iron uptake regulator (Fur) protein.
AB  - The ferric uptake regulator (Fur) box-like sequence was located upstream of the
      serine protease-encoding gene (aprII) from a marine bacterium, Alteromonas sp.
      strain O-7. To clarify whether the production of AprII (the gene product of
      aprII) is regulated by the environmental iron concentrations, this strain was
      cultured under iron-depleted or iron-rich conditions and the level of AprII in
      the culture supernatant was analyzed by Western blotting. The production of AprII
      was significantly repressed under iron-rich conditions. Northern hybridization
      analysis demonstrated that AprII biosynthesis was regulated by iron through the
      control of transcription. These results indicate that aprII is a new member of
      the iron regulon and plays an important role in the iron acquisition system of
      the strain. Furthermore, the gene encoding Fur was cloned and sequenced. The
      deduced amino acid sequence of the cloned Fur showed high sequence similarity
      with that from gram-negative bacteria.

PMID- 10966391
TI  - Development and characterization of diamondback moth resistance to transgenic
      broccoli expressing high levels of Cry1C.
AB  - A field-collected colony of the diamondback moth, Plutella xylostella, had 31
      fold resistance to Cry1C protoxin of Bacillus thuringiensis. After 24 generations
      of selection with Cry1C protoxin and transgenic broccoli expressing a Cry1C
      protein, the resistance that developed was high enough that neonates of the
      resistant strain could complete their entire life cycle on transgenic broccoli
      expressing high levels of Cry1C. After 26 generations of selection, the
      resistance ratios of this strain to Cry1C protoxin were 12,400- and 63,100-fold,
      respectively, for the neonates and second instars by a leaf dip assay. The
      resistance remained stable until generation 38 (G38) under continuous selection
      but decreased to 235-fold at G38 when selection ceased at G28. The Cry1C
      resistance in this strain was seen to be inherited as an autosomal and
      incompletely recessive factor or factors when evaluated using a leaf dip assay
      and recessive when evaluated using Cry1C transgenic broccoli. Saturable binding
      of (125)I-Cry1C was found with brush border membrane vesicles (BBMV) from both
      susceptible and Cry1C-resistant strains. Significant differences in Cry1C binding
      to BBMV from the two strains were detected. BBMV from the resistant strain had
      about sevenfold-lower affinity for Cry1C and threefold-higher binding site
      concentration than BBMV from the susceptible strain. The overall Cry1C binding
      affinity was just 2.5-fold higher for BBMV from the susceptible strain than it
      was for BBMV from the resistant strain. These results suggest that reduced
      binding is not the major mechanism of resistance to Cry1C.

PMID- 10966392
TI  - Rapid virus production and removal as measured with fluorescently labeled viruses
      as tracers.
AB  - Pelagic marine viruses have been shown to cause significant mortality of
      heterotrophic bacteria, cyanobacteria, and phytoplankton. It was previously
      demonstrated, in nearshore California waters, that viruses contributed to up to
      50% of bacterial mortality, comparable to protists. However, in less productive
      waters, rates of virus production and removal and estimates of virus-mediated
      bacterial mortality have been difficult to determine. We have measured rates of
      virus production and removal, in nearshore and offshore California waters, by
      using fluorescently labeled viruses (FLV) as tracers. Our approach is
      mathematically similar to the isotope dilution technique, employed in the past to
      simultaneously measure the release and uptake of ammonia and amino acids. The
      results indicated overall virus removal rates in the dark ranging from 1.8 to
      6.2% h(-1) and production rates in the dark ranging from 1.9 to 6.1% h(-1),
      corresponding to turnover times of virus populations of 1 to 2 days, even in
      oligotrophic offshore waters. Virus removal rates determined by the FLV tracer
      method were compared to rates of virus degradation, determined at the same
      locations by radiolabeling methods, and were similar even though the current FLV
      method is suitable for only dark incubations. Our results support previous
      findings that virus impacts on bacterial populations may be more important in
      some environments and less so in others. This new method can be used to determine
      rates of virus degradation, production, and turnover in eutrophic, mesotrophic,
      and oligotrophic waters and will provide important inputs for future
      investigations of microbial food webs.

PMID- 10966394
TI  - Relative contributions of bacteria, protozoa, and fungi to in vitro degradation
      of orchard grass cell walls and their interactions.
AB  - To assess the relative contributions of microbial groups (bacteria, protozoa, and
      fungi) in rumen fluids to the overall process of plant cell wall digestion in the
      rumen, representatives of these groups were selected by physical and chemical
      treatments of whole rumen fluid and used to construct an artificial rumen
      ecosystem. Physical treatments involved homogenization, centrifugation,
      filtration, and heat sterilization. Chemical treatments involved the addition of
      antibiotics and various chemicals to rumen fluid. To evaluate the potential
      activity and relative contribution to degradation of cell walls by specific
      microbial groups, the following fractions were prepared: a positive system (whole
      ruminal fluid), a bacterial (B) system, a protozoal (P) system, a fungal (F)
      system, and a negative system (cell-free rumen fluid). To assess the interactions
      between specific microbial fractions, mixed cultures (B+P, B+F, and P+F systems)
      were also assigned. Patterns of degradation due to the various treatments
      resulted in three distinct groups of data based on the degradation rate of cell
      wall material and on cell wall-degrading enzyme activities. The order of
      degradation was as follows: positive and F systems > B system > negative and P
      systems. Therefore, fungal activity was responsible for most of the cell wall
      degradation. Cell wall degradation by the anaerobic bacterial fraction was
      significantly less than by the fungal fraction, and the protozoal fraction failed
      to grow under the conditions used. In general, in the mixed culture systems the
      coculture systems demonstrated a decrease in cellulolysis compared with that of
      the monoculture systems. When one microbial fraction was associated with another
      microbial fraction, two types of results were obtained. The protozoal fraction
      inhibited cellulolysis of cell wall material by both the bacterial and the fungal
      fractions, while in the coculture between the bacterial fraction and the fungal
      fraction a synergistic interaction was detected.

PMID- 10966393
TI  - Novel bacterial and archaeal lineages from an in situ growth chamber deployed at
      a Mid-Atlantic Ridge hydrothermal vent.
AB  - The phylogenetic diversity was determined for a microbial community obtained from
      an in situ growth chamber placed on a deep-sea hydrothermal vent on the Mid
      Atlantic Ridge (23 degrees 22' N, 44 degrees 57' W). The chamber was deployed for
      5 days, and the temperature within the chamber gradually decreased from 70 to 20
      degrees C. Upon retrieval of the chamber, the DNA was extracted and the small
      subunit rRNA genes (16S rDNA) were amplified by PCR using primers specific for
      the Archaea or Bacteria domain and cloned. Unique rDNA sequences were identified
      by restriction fragment length polymorphisms, and 38 different archaeal and
      bacterial phylotypes were identified from the 85 clones screened. The majority of
      the archaeal sequences were affiliated with the Thermococcales (71%) and
      Archaeoglobales (22%) orders. A sequence belonging to the Thermoplasmales
      confirms that thermoacidophiles may have escaped enrichment culturing attempts of
      deep-sea hydrothermal vent samples. Additional sequences that represented deeply
      rooted lineages in the low-temperature eurarchaeal (marine group II) and
      crenarchaeal clades were obtained. The majority of the bacterial sequences
      obtained were restricted to the Aquificales (18%), the epsilon subclass of the
      Proteobacteria (epsilon-Proteobacteria) (40%), and the genus Desulfurobacterium
      (25%). Most of the clones (28%) were confined to a monophyletic clade within the
      epsilon-Proteobacteria with no known close relatives. The prevalence of clones
      related to thermophilic microbes that use hydrogen as an electron donor and
      sulfur compounds (S(0), SO(4), thiosulfate) indicates the importance of hydrogen
      oxidation and sulfur metabolism at deep-sea hydrothermal vents. The presence of
      sequences that are related to sequences from hyperthermophiles, moderate
      thermophiles, and mesophiles suggests that the diversity obtained from this
      analysis may reflect the microbial succession that occurred in response to the
      shift in temperature and possible associated changes in the chemistry of the
      hydrothermal fluid.

PMID- 10966396
TI  - Ferrous iron-dependent volatilization of mercury by the plasma membrane of
      Thiobacillus ferrooxidans.
AB  - Of 100 strains of iron-oxidizing bacteria isolated, Thiobacillus ferrooxidans SUG
      2-2 was the most resistant to mercury toxicity and could grow in an Fe(2+) medium
      (pH 2.5) supplemented with 6 microM Hg(2+). In contrast, T. ferrooxidans AP19-3,
      a mercury-sensitive T. ferrooxidans strain, could not grow with 0.7 microM
      Hg(2+). When incubated for 3 h in a salt solution (pH 2.5) with 0.7 microM
      Hg(2+), resting cells of resistant and sensitive strains volatilized
      approximately 20 and 1.7%, respectively, of the total mercury added. The amount
      of mercury volatilized by resistant cells, but not by sensitive cells, increased
      to 62% when Fe(2+) was added. The optimum pH and temperature for mercury
      volatilization activity were 2.3 and 30 degrees C, respectively. Sodium cyanide,
      sodium molybdate, sodium tungstate, and silver nitrate strongly inhibited the
      Fe(2+)-dependent mercury volatilization activity of T. ferrooxidans. When
      incubated in a salt solution (pH 3.8) with 0.7 microM Hg(2+) and 1 mM Fe(2+),
      plasma membranes prepared from resistant cells volatilized 48% of the total
      mercury added after 5 days of incubation. However, the membrane did not have
      mercury reductase activity with NADPH as an electron donor. Fe(2+)-dependent
      mercury volatilization activity was not observed with plasma membranes pretreated
      with 2 mM sodium cyanide. Rusticyanin from resistant cells activated iron
      oxidation activity of the plasma membrane and activated the Fe(2+)-dependent
      mercury volatilization activity of the plasma membrane.

PMID- 10966395
TI  - Molecular analysis of diazotroph diversity in the rhizosphere of the smooth
      cordgrass, Spartina alterniflora.
AB  - N(2) fixation by diazotrophic bacteria associated with the roots of the smooth
      cordgrass, Spartina alterniflora, is an important source of new nitrogen in many
      salt marsh ecosystems. However, the diversity and phylogenetic affiliations of
      these rhizosphere diazotrophs are unknown. Denaturing gradient gel
      electrophoresis (DGGE) of PCR-amplified nifH sequence segments was used in
      previous studies to examine the stability and dynamics of the Spartina
      rhizosphere diazotroph assemblages in the North Inlet salt marsh, near
      Georgetown, S.C. In this study, plugs were taken from gel bands from
      representative DGGE gels, the nifH amplimers were recovered and cloned, and their
      sequences were determined. A total of 59 sequences were recovered, and the amino
      acid sequences predicted from them were aligned with sequences from known and
      unknown diazotrophs in order to determine the types of organisms present in the
      Spartina rhizosphere. We recovered numerous sequences from diazotrophs in the
      gamma subdivision of the division Proteobacteria (gamma-Proteobacteria) and from
      various anaerobic diazotrophs. Diazotrophs in the alpha-Proteobacteria were
      poorly represented. None of the Spartina rhizosphere DGGE band sequences were
      identical to any known or previously recovered environmental nifH sequences. The
      Spartina rhizosphere diazotroph assemblage is very diverse and apparently
      consists mainly of unknown organisms.

PMID- 10966397
TI  - Rapid characterization of spores of Bacillus cereus group bacteria by matrix
      assisted laser desorption-ionization time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption-ionization (MALDI) time-of-flight mass
      spectrometry was used to characterize the spores of 14 microorganisms of the
      Bacillus cereus group. This group includes the four Bacillus species B.
      anthracis, B. cereus, B. mycoides, and B. thuringiensis. MALDI mass spectra
      obtained from whole bacterial spores showed many similarities between the
      species, except for B. mycoides. At the same time, unique mass spectra could be
      obtained for the different B. cereus and B. thuringiensis strains, allowing for
      differentiation at the strain level. To increase the number of detectable
      biomarkers in the usually peak-poor MALDI spectra of spores, the spores were
      treated by corona plasma discharge (CPD) or sonicated prior to MALDI analysis.
      Spectra of sonicated or CPD-treated spores displayed an ensemble of biomarkers
      common for B. cereus group bacteria. Based on the spectra available, these
      biomarkers differentiate B. cereus group spores from those of Bacillus subtilis
      and Bacillus globigii. The effect of growth medium on MALDI spectra of spores was
      also explored.

PMID- 10966398
TI  - Metabolic engineering of Lactobacillus helveticus CNRZ32 for production of pure L
      (+)-lactic acid.
AB  - Expression of D-(-)-lactate dehydrogenase (D-LDH) and L-(+)-LDH genes (ldhD and
      ldhL, respectively) and production of D-(-)- and L-(+)-lactic acid were studied
      in Lactobacillus helveticus CNRZ32. In order to develop a host for production of
      pure L-(+)-isomer of lactic acid, two ldhD-negative L. helveticus CNRZ32 strains
      were constructed using gene replacement. One of the strains was constructed by
      deleting the promoter region of the ldhD gene, and the other was constructed by
      replacing the structural gene of ldhD with an additional copy of the structural
      gene (ldhL) of L-LDH of the same species. The resulting strains were designated
      GRL86 and GRL89, respectively. In strain GRL89, the second copy of the ldhL
      structural gene was expressed under the ldhD promoter. The two D-LDH-negative
      strains produced only L-(+)-lactic acid in an amount equal to the total lactate
      produced by the wild type. The maximum L-LDH activity was found to be 53 and 93%
      higher in GRL86 and GRL89, respectively, than in the wild-type strain.
      Furthermore, process variables for L-(+)-lactic acid production by GRL89 were
      optimized using statistical experimental design and response surface methodology.
      The temperature and pH optima were 41 degrees C and pH 5.9. At low pH, when the
      growth and lactic acid production are uncoupled, strain GRL89 produced
      approximately 20% more lactic acid than GRL86.

PMID- 10966399
TI  - Phylogeny of microorganisms populating a thick, subaerial, predominantly
      lithotrophic biofilm at an extreme acid mine drainage site.
AB  - An unusually thick ( approximately 1 cm) slime developed on a slump of finely
      disseminated pyrite ore within an extreme acid mine drainage site at Iron
      Mountain, near Redding, Calif. The slime was studied over the period of 1 year.
      The subaerial form of the slime distinguished it from more typical submerged
      streamers. Phylogenetic analysis of 16S rRNA genes revealed a diversity of
      sequences that were mostly novel. Nearest relatives to the majority of sequences
      came from iron-oxidizing acidophiles, and it appears that iron oxidation is the
      predominant metabolic characteristic of the organisms in the slime. The most
      abundant of the 16S rRNA genes detected were from organisms related to
      Leptospirillum species. The dominant sequence (71% of clones) may represent a new
      genus. Sequences within the Archaea of the Thermoplasmales lineage were detected.
      Most of these were only distantly related to known microorganisms. Also,
      sequences affiliating with Acidimicrobium were detected. Some of these were
      closely related to "Ferromicrobium acidophilus," and others were affiliated with
      a lineage only represented by environmental clones. Unexpectedly, sequences that
      affiliated within the delta subdivision of the Proteobacteria were detected. The
      predominant metabolic feature of bacteria of this subdivision is anaerobic
      sulfate or metal reduction. Thus, microenvironments of low redox potential
      possibly exist in the predominantly oxidizing environments of the slime. These
      results expand our knowledge of the biodiversity of acid mine drainage
      environments and extend our understanding of the ecology of extremely acidic
      systems.

PMID- 10966400
TI  - Biotransformation of the antimelanoma agent betulinic acid by Bacillus megaterium
      ATCC 13368.
AB  - Microbial transformation of the antimelanoma agent betulinic acid was studied.
      The main objective of this study was to utilize microorganisms as in vitro models
      to predict and prepare potential mammalian metabolites of this compound.
      Preparative-scale biotransformation with resting-cell suspensions of Bacillus
      megaterium ATCC 13368 resulted in the production of four metabolites, which were
      identified as 3-oxo-lup-20(29)-en-28-oic acid, 3-oxo-11alpha-hydroxy-lup-20(29)
      en-28-oic acid, 1beta-hydroxy-3-oxo-lup-20(29)-en-28-oic acid, and 3beta,7beta,
      15alpha-trihydroxy-lup-20(29)-en-28-oic acid based on nuclear magnetic resonance
      and high-resolution mass spectral analyses. In addition, the antimelanoma
      activities of these metabolites were evaluated with two human melanoma cell
      lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).

PMID- 10966401
TI  - Characterization of the minimal replicon of a cryptic Deinococcus radiodurans
      SARK plasmid and development of versatile Escherichia coli-D. radiodurans shuttle
      vectors.
AB  - The nucleotide sequence of a 12-kb fragment of the cryptic Deinococcus
      radiodurans SARK plasmid pUE10 was determined, in order to direct the development
      of small, versatile cloning systems for Deinococcus. Annotation of the sequence
      revealed 12 possible open reading frames. Among these are the repU and resU
      genes, the predicted products of which share similarity with replication proteins
      and site-specific resolvases, respectively. The products of both genes were
      demonstrated using an overexpression system in Escherichia coli. RepU was found
      to be required for replication, and ResU was found to be required for stable
      maintenance of pUE10 derivatives. Gel shift analysis using purified His-tagged
      RepU identified putative binding sites and suggested that RepU may be involved in
      both replication initiation and autoregulation of repU expression. In addition, a
      gene encoding a possible antirestriction protein was found, which was shown to be
      required for high transformation frequencies. The arrangement of the replication
      region and putative replication genes for this plasmid from D. radiodurans strain
      SARK is similar to that for plasmids found in Thermus but not to that for the
      45.7-kb plasmid found in D. radiodurans strain R1. The minimal region required
      for autonomous replication in D. radiodurans was determined by sequential
      deletion of segments from the 12-kb fragment. The resulting minimal replicon,
      which consists of approximately 2.6 kb, was used for the construction of a
      shuttle vector for E. coli and D. radiodurans. This vector, pRAD1, is a
      convenient general-purpose cloning vector. In addition, pRAD1 was used to
      generate a promoter probe vector, and a plasmid containing lacZ and a Deinococcus
      promoter was shown to efficiently express LacZ.

PMID- 10966402
TI  - Mathematical analysis of growth and interaction dynamics of streptomycetes and a
      bacteriophage in soil.
AB  - We observed the infection cycle of the temperate actinophage KC301 in relation to
      the growth of its host Streptomyces lividans TK24 in sterile soil microcosms.
      Despite a large increase in phage population following germination of host
      spores, there was no observable impact on host population numbers as measured by
      direct plate counts. The only change in the host population following infection
      was the establishment of a small subpopulation of KC301 lysogens. The interaction
      of S. lividans and KC301 in soil was analyzed with a population-dynamic
      mathematical model to determine the underlying mechanisms of this low
      susceptibility to phage attack relative to aquatic environments. This analysis
      suggests that the soil environment is a highly significant component of the phage
      host interaction, an idea consistent with earlier observations on the importance
      of the environment in determining host growth and phage-host dynamics. Our
      results demonstrate that the accepted phage-host interaction and host life cycle,
      as determined from agar plate studies and liquid culture, is sufficient for
      quantitative agreement with observations in soil, using soil-determined rates.
      There are four significant effects of the soil environment: (i) newly germinated
      spores are more susceptible to phage lysis than are hyphae of developed mycelia,
      (ii) substrate mycelia in mature colonies adsorb about 98% of the total phage
      protecting susceptible young hyphae from infection, (iii) the burst size of KC301
      is large in soil (>150, 90% confidence) relative to that observed in liquid
      culture (120, standard error of the mean [SEM], 6), and (iv) there is no
      measurable impact on the host in terms of reduced growth by the phage. We
      hypothesize that spatial heterogeneity is the principal cause of these effects
      and is the primary determinant in bacterial escape of phage lysis in soil.

PMID- 10966403
TI  - Ethylene removal at low temperatures under biofilter and batch conditions.
AB  - Removal of the plant hormone ethylene (C(2)H(4)) is often required by
      horticultural storage facilities, which are operated at temperatures below 10
      degrees C. The aim of this study was to demonstrate an efficient, biological
      C(2)H(4) removal under such low-temperature conditions. Peat-soil, acclimated to
      degradation of C(2)H(4), was packed in a biofilter (687 cm(3)) and subjected to
      an airflow ( approximately 73 ml min(-1)) with 2 ppm (microl liter(-1)) C(2)H(4).
      The C(2)H(4) removal efficiencies achieved at 20, 10, and 5 degrees C,
      respectively, were 99.0, 98.8, and 98.4%. This corresponded to C(2)H(4) levels of
      0.022 to 0.032 ppm in the biofilter outlet air. At 2 degrees C, the average
      C(2)H(4) removal efficiency dropped to 83%. The detailed temperature response of
      C(2)H(4) removal was tested under batch conditions by incubation of 1-g soil
      samples in a temperature gradient ranging from 0 to 29 degrees C with increments
      of 1 degrees C. The C(2)H(4) removal rate was highest at 26 degrees C (0.85
      microg of C(2)H(4) g [dry weight](-1) h(-1)), but remained at levels of 0.14 to
      0.28 microg of C(2)H(4) g (dry weight)(-1) h(-1) at 0 to 10 degrees C. At 35 to
      40 degrees C, the C(2)H(4) removal rate was negligible (0.02 to 0.06 microg of
      C(2)H(4) g [dry weight](-1) h(-1)). The Q(10) (i.e., the ratio of rates 10
      degrees C apart) for C(2)H(4) removal was 1.9 for the interval 0 to 10 degrees C.
      In conclusion, the present results demonstrated microbial C(2)H(4) removal, which
      proceeded at 0 to 2 degrees C and produced a moderately psychrophilic temperature
      response.

PMID- 10966404
TI  - Distribution of oxytetracycline resistance plasmids between aeromonads in
      hospital and aquaculture environments: implication of Tn1721 in dissemination of
      the tetracycline resistance determinant tet A.
AB  - Oxytetracycline-resistant (OT(r)) mesophilic aeromonads were recovered from
      untreated hospital effluent (72 isolates) and from fish farm hatchery tanks (91
      isolates) at sites within the English Lake District, Cumbria, England. The
      transfer of OT(r) plasmids from these isolates was investigated. Using
      Escherichia coli J53-1 as a recipient, 11 isolates from the hospital site and 6
      isolates from the fish farm site transferred OT(r) plasmids (designated pFBAOT1
      to 17). Original isolates were identified using fatty acid methyl ester and
      fluorescent amplified fragment length polymorphism comparisons as either
      Aeromonas hydrophila HG3 (eight isolates), A. veronii b.v. sobria HG8 (six
      isolates), and A. caviae HGB5 (one isolate). One isolate remained unidentified,
      and one could not be assigned a taxonomic designation beyond the genus level.
      Plasmids pFBAOT1 to -17 were screened for the presence of the tetracycline
      resistance determinants Tet A to E and Tet G. Only determinant Tet A (10
      plasmids) was detected in these plasmids, with 7 tet gene determinants remaining
      unclassified. In all cases, Tet A was located on a 5.5-kb EcoRI restriction
      fragment. Hybridization with inc-rep probes N, P, Q, W, and U showed pFBAOT3, -4,
      -5, -6, -7, -9, and -11, from the hospital environment, to be IncU plasmids.
      Further, restriction fragment length polymorphism (RFLP) analyses and DNA probing
      demonstrated that pFBAOT plasmids were closely related to IncU OT(r) plasmids
      pASOT, pASOT2, pASOT3, pRAS1 (originally isolated from A. salmonicida strains
      from fish farms in Scotland and Norway, respectively), and pIE420 (isolated from
      a German hospital E. coli strain). In addition, DNA analyses demonstrated that
      plasmids pRAS1 and pIE420 had identical RFLP profiles and that all fragments
      hybridized to each other. The presence of tetracycline resistance transposon
      Tn1721 in its entirety or in a truncated form in these plasmids was demonstrated.
      These results provided direct evidence that related tetracycline resistance
      encoding plasmids have disseminated between different Aeromonas species and E.
      coli and between the human and aquaculture environments in distinct geographical
      locations. Collectively, these findings provide evidence to support the
      hypothesis that the aquaculture and human compartments of the environment behave
      as a single interactive compartment.

PMID- 10966405
TI  - Production and consumption of nitric oxide by three methanotrophic bacteria.
AB  - We studied nitrogen oxide production and consumption by methanotrophs
      Methylobacter luteus (group I), Methylosinus trichosporium OB3b (group II), and
      an isolate from a hardwood swamp soil, here identified by 16S ribosomal DNA
      sequencing as Methylobacter sp. strain T20 (group I). All could consume nitric
      oxide (nitrogen monoxide, NO), and produce small amounts of nitrous oxide
      (N(2)O). Only Methylobacter strain T20 produced large amounts of NO (>250 parts
      per million by volume [ppmv] in the headspace) at specific activities of up to
      2.0 x 10(-17) mol of NO cell(-1) day(-1), mostly after a culture became O(2)
      limited. Production of NO by strain T20 occurred mostly in nitrate-containing
      medium under anaerobic or nearly anaerobic conditions, was inhibited by chlorate,
      tungstate, and O(2), and required CH(4). Denitrification (methanol-supported
      N(2)O production from nitrate in the presence of acetylene) could not be detected
      and thus did not appear to be involved in the production of NO. Furthermore,
      cd(1) and Cu nitrite reductases, NO reductase, and N(2)O reductase could not be
      detected by PCR amplification of the nirS, nirK, norB, and nosZ genes,
      respectively. M. luteus and M. trichosporium produced some NO in ammonium
      containing medium under aerobic conditions, likely as a result of methanotrophic
      nitrification and chemical decomposition of nitrite. For Methylobacter strain
      T20, arginine did not stimulate NO production under aerobiosis, suggesting that
      NO synthase was not involved. We conclude that strain T20 causes assimilatory
      reduction of nitrate to nitrite, which then decomposes chemically to NO. The
      production of NO by methanotrophs such as Methylobacter strain T20 could be of
      ecological significance in habitats near aerobic-anaerobic interfaces where
      fluctuating O(2) and nitrate availability occur.

PMID- 10966406
TI  - Production of angiotensin-I-converting-enzyme-inhibitory peptides in fermented
      milks started by Lactobacillus delbrueckii subsp. bulgaricus SS1 and Lactococcus
      lactis subsp. cremoris FT4.
AB  - Two fermented milks containing angiotensin-I-converting-enzyme (ACE)-inhibitory
      peptides were produced by using selected Lactobacillus delbrueckii subsp.
      bulgaricus SS1 and L. lactis subsp. cremoris FT4. The pH 4.6-soluble nitrogen
      fraction of the two fermented milks was fractionated by reversed-phase fast
      protein liquid chromatography. The fractions which showed the highest ACE
      inhibitory indexes were further purified, and the related peptides were sequenced
      by tandem fast atom bombardment-mass spectrometry. The most inhibitory fractions
      of the milk fermented by L. delbrueckii subsp. bulgaricus SS1 contained the
      sequences of beta-casein (beta-CN) fragment 6-14 (f6-14), f7-14, f73-82, f74-82,
      and f75-82. Those from the milk fermented by L. lactis subsp. cremoris FT4
      contained the sequences of beta-CN f7-14, f47-52, and f169-175 and kappa-CN f155
      160 and f152-160. Most of these sequences had features in common with other ACE
      inhibitory peptides reported in the literature. In particular, the beta-CN f47-52
      sequence had high homology with that of angiotensin-II. Some of these peptides
      were chemically synthesized. The 50% inhibitory concentrations (IC(50)s) of the
      crude purified fractions containing the peptide mixture were very low (8.0 to
      11.2 mg/liter). When the synthesized peptides were used individually, the ACE
      inhibitory activity was confirmed but the IC(50)s increased considerably. A
      strengthened inhibitory effect of the peptide mixtures with respect to the
      activity of individual peptides was presumed. Once generated, the inhibitory
      peptides were resistant to further proteolysis either during dairy processing or
      by trypsin and chymotrypsin.

PMID- 10966407
TI  - Starvation improves survival of bacteria introduced into activated sludge.
AB  - A phenol-degrading bacterium, Ralstonia eutropha E2, was grown in Luria-Bertani
      (LB) medium or in an inorganic medium (called MP) supplemented with phenol and
      harvested at the late-exponential-growth phase. Phenol-acclimated activated
      sludge was inoculated with the E2 cells immediately after harvest or after
      starvation in MP for 2 or 7 days. The densities of the E2 populations in the
      activated sludge were then monitored by quantitative PCR. The E2 cells grown on
      phenol and starved for 2 days (P-2 cells) survived in the activated sludge better
      than those treated differently: the population density of the P-2 cells 7 days
      after their inoculation was 50 to 100 times higher than the population density of
      E2 cells without starvation or that with 7-day starvation. LB medium-grown cells
      either starved or nonstarved were rapidly eliminated from the sludge. The P-2
      cells showed a high cell surface hydrophobicity and retained metabolic
      activities. Cells otherwise prepared did not have one of these two features. From
      these observations, it is assumed that hydrophobic cell surface and metabolic
      activities higher than certain levels were required for the inoculated bacteria
      to survive in the activated sludge. Reverse transcriptase PCR analyses showed
      that the P-2 cells initiated the expression of phenol hydroxylase within 1 day of
      their inoculation into the sludge. These results suggest the utility of a short
      starvation treatment for improving the efficacy of bioaugumentation.

PMID- 10966408
TI  - Contribution of dps to acid stress tolerance and oxidative stress tolerance in
      Escherichia coli O157:H7.
AB  - An Escherichia coli O157:H7 dps::nptI mutant (FRIK 47991) was generated, and its
      survival was compared to that of the parent in HCl (synthetic gastric fluid, pH
      1.8) and hydrogen peroxide (15 mM) challenges. The survival of the mutant in log
      phase (5-h culture) was significantly impaired (4-log(10)-CFU/ml reduction)
      compared to that of the parent strain (ca. 1.0-log(10)-CFU/ml reduction) after a
      standard 3-h acid challenge. Early-stationary-phase cells (12-h culture) of the
      mutant decreased by ca. 4 log(10) CFU/ml while the parent strain decreased by
      approximately 2 log(10) CFU/ml. No significant differences in the survival of
      late-stationary-phase cells (24-h culture) between the parent strain and the
      mutant were observed, although numbers of the parent strain declined less in the
      initial 1 h of acid challenge. FRIK 47991 was more sensitive to hydrogen peroxide
      challenge than was the parent strain, although survival improved in stationary
      phase. Complementation of the mutant with a functional dps gene restored acid and
      hydrogen peroxide tolerance to levels equal to or greater than those exhibited by
      the parent strain. These results demonstrate that decreases in survival were from
      the absence of Dps or a protein regulated by Dps. The results from this study
      establish that Dps contributes to acid tolerance in E. coli O157:H7 and confirm
      the importance of Dps in oxidative stress protection.

PMID- 10966409
TI  - Amplified fragment length polymorphism analysis of Campylobacter jejuni strains
      isolated from chickens and from patients with gastroenteritis or Guillain-Barre
      or Miller Fisher syndrome.
AB  - The high-resolution genotyping method of amplified fragment length polymorphism
      (AFLP) analysis was used to study the genetic relationships between Campylobacter
      jejuni strains infecting chickens (n = 54) and those causing gastroenteritis in
      humans (n = 53). In addition, C. jejuni strains associated with the development
      of Guillain-Barre syndrome (GBS) (n = 14) and Miller Fisher syndrome (MFS) (n =
      4), two related acute paralytic syndromes in human, were included. Strains were
      isolated between 1989 and 1998 in The Netherlands. The AFLP banding patterns were
      analyzed with correlation-based and band-based similarity coefficients and UPGMA
      (unweighted pair group method using average linkages) cluster analysis. All C.
      jejuni strains showed highly heterogeneous fingerprints, and no fingerprints
      exclusive for chicken strains or for human strains were obtained. All strains
      were separated in two distinct genetic groups. In group A the percentage of human
      strains was significantly higher and may be an indication that genotypes of this
      group are more frequently associated with human diseases. We conclude that C.
      jejuni from chickens cannot be distinguished from human strains and that GBS or
      MFS related strains do not belong to a distinct genetic group.

PMID- 10966410
TI  - Additional evidence that juvenile oyster disease is caused by a member of the
      Roseobacter group and colonization of nonaffected animals by Stappia stellulata
      like strains.
AB  - Juvenile oyster disease (JOD) causes significant annual mortalities of hatchery
      produced Eastern oysters, Crassostrea virginica, cultured in the Northeast. We
      have reported that a novel species of the alpha-proteobacteria Roseobacter group
      (designated CVSP) was numerically dominant in JOD-affected animals sampled during
      the 1997 epizootic on the Damariscotta River, Maine. In this study we report the
      isolation of CVSP bacteria from JOD-affected oysters during three separate
      epizootics in 1998. These bacteria were not detected in nonaffected oysters at
      the enzootic site, nor in animals raised at a JOD-free site. Animals raised at
      the JOD enzootic site that were unaffected by JOD were stably and persistently
      colonized by Stappia stellulata-like strains. These isolates (designated M1)
      inhibited the growth of CVSP bacteria in a disk-diffusion assay and thus may have
      prevented colonization of these animals by CVSP bacteria in situ. Laboratory
      maintained C. virginica injected with CVSP bacteria experienced statistically
      significant elevated mortalities compared to controls, and CVSP bacteria were
      recovered from these animals during the mortality events. Together, these results
      provide additional evidence that CVSP bacteria are the etiological agent of JOD.
      Further, there are no other descriptions of specific marine alpha-proteobacteria
      that have been successfully cultivated from a defined animal host. Thus, this
      system presents an opportunity to investigate both bacterial and host factors
      involved in the establishment of such associations and the role of the
      invertebrate host in the ecology of these marine alpha-proteobacteria.

PMID- 10966411
TI  - Variable expressions of Staphylococcus aureus bicomponent leucotoxins
      semiquantified by competitive reverse transcription-PCR.
AB  - A competitive reverse transcription-PCR method was developed for the
      semiquantitation of the expression of genes encoding bicomponent leucotoxins of
      Staphylococcus aureus, e.g., Panton-Valentine leucocidin (lukPV), gamma-hemolysin
      (hlgA and hlgCB), and LukE-LukD (lukED). The optimization procedure included RNA
      preparation; reverse transcription; the use of various amounts of enzymes,
      antisense primer, and RNA; and the final amplification chain reaction.
      Reproducible results were obtained, with sensitivity for detection of cDNA within
      the range of 1 mRNA/10(4) CFU to 10(2) mRNA/CFU, depending on the gene. Both
      specific mRNAs were more significantly expressed at the late-exponential phase of
      growth. Expression was about 100-fold higher in yeast extract-Casamino Acids
      pyruvate medium than in heart infusion medium. Expression of the widely
      distributed gamma-hemolysin locus in the NTCC 8178 strain was around 10-fold
      diminished compared with that in the ATCC 49775 strain. Because of the lower
      level of hlgA expression, the corresponding protein, which is generally not
      abundant in culture supernatant, should be investigated for its contribution to
      the leucotoxin-associated virulence. The agr, sar, and agr sar mutant strains
      revealed a great dependence with regard to leucotoxin expression on the global
      regulatory system in S. aureus, except that expression of hlgA was not affected
      in the agr mutant.

PMID- 10966412
TI  - Engineering hydrogen sulfide production and cadmium removal by expression of the
      thiosulfate reductase gene (phsABC) from Salmonella enterica serovar typhimurium
      in Escherichia coli.
AB  - The thiosulfate reductase gene (phsABC) from Salmonella enterica serovar
      Typhimurium was expressed in Escherichia coli to overproduce hydrogen sulfide
      from thiosulfate for heavy metal removal (or precipitation). A 5.1-kb DNA
      fragment containing phsABC was inserted into the pMB1-based, high-copy, isopropyl
      beta-D-thiogalactopyranoside-inducible expression vector pTrc99A and the RK2
      based, medium-copy, m-toluate-inducible expression vector pJB866, resulting in
      plasmids pSB74 and pSB77. A 3. 7-kb DNA fragment, excluding putative promoter and
      regulatory regions, was inserted into the same vectors, making plasmids pSB103
      and pSB107. E. coli DH5alpha strains harboring the phsABC constructs showed
      higher thiosulfate reductase activity and produced significantly more sulfide
      than the control strains under both aerobic and anaerobic conditions. Among the
      four phsABC constructs, E. coli DH5alpha (pSB74) produced thiosulfate reductase
      at the highest level and removed the most cadmium from solution under anaerobic
      conditions: 98% of all concentrations up to 150 microM and 91% of 200 microM. In
      contrast, a negative control did not produce any measurable sulfide and removed
      very little cadmium from solution. Energy-dispersive X-ray spectroscopy revealed
      that the metal removed from solution precipitated as a complex of cadmium and
      sulfur, most likely cadmium sulfide.

PMID- 10966413
TI  - A novel gene encoding xanthan lyase of Paenibacillus alginolyticus strain XL-1.
AB  - Xanthan-modifying enzymes are powerful tools in studying structure-function
      relationships of this polysaccharide. One of these modifying enzymes is xanthan
      lyase, which removes the terminal side chain residue of xanthan. In this paper,
      the cloning and sequencing of the first xanthan lyase-encoding gene is described,
      i. e., the xalA gene, encoding pyruvated mannose-specific xanthan lyase of
      Paenibacillus alginolyticus XL-1. The xalA gene encoded a 100, 823-Da protein,
      including a 36-amino-acid signal sequence. The 96, 887-Da mature enzyme could be
      expressed functionally in Escherichia coli. Like the native enzyme, the
      recombinant enzyme showed no activity on depyruvated xanthan. Compared to
      production by P. alginolyticus, a 30-fold increase in volumetric productivity of
      soluble xanthan lyase was achieved by heterologous production in E. coli. The
      recombinant xanthan lyase was used to produce modified xanthan, which showed a
      dramatic loss of the capacity to form gels with locust bean gum.

PMID- 10966414
TI  - Phylogenetic analysis of bacterial communities in mesophilic and thermophilic
      bioreactors treating pharmaceutical wastewater.
AB  - The phylogenetic diversity of the bacterial communities supported by a seven
      stage, full-scale biological wastewater treatment plant was studied. These
      reactors were operated at both mesophilic (28 to 32 degrees C) and thermophilic
      (50 to 58 degrees C) temperatures. Community fingerprint analysis by denaturing
      gradient gel electrophoresis (DGGE) of the PCR-amplified V3 region of the 16S
      rRNA gene from the domain Bacteria revealed that these seven reactors supported
      three distinct microbial communities. A band-counting analysis of the PCR-DGGE
      results suggested that elevated reactor temperatures corresponded with reduced
      species richness. Cloning of nearly complete 16S rRNA genes also suggested a
      reduced species richness in the thermophilic reactors by comparing the number of
      clones with different nucleotide inserts versus the total number of clones
      screened. While these results imply that elevated temperature can reduce species
      richness, other factors also could have impacted the number of populations that
      were detected. Nearly complete 16S rDNA sequence analysis showed that the
      thermophilic reactors were dominated by members from the beta subdivision of the
      division Proteobacteria (beta-proteobacteria) in addition to anaerobic phylotypes
      from the low-G+C gram-positive and Synergistes divisions. The mesophilic
      reactors, however, included at least six bacterial divisions, including Cytophaga
      Flavobacterium-Bacteroides, Synergistes, Planctomycetes, low-G+C gram-positives,
      Holophaga-Acidobacterium, and Proteobacteria (alpha-proteobacteria, beta
      proteobacteria, gamma-proteobacteria and delta-proteobacteria subdivisions). The
      two PCR-based techniques detected the presence of similar bacterial populations
      but failed to coincide on the relative distribution of these phylotypes. This
      suggested that at least one of these methods is insufficiently quantitative to
      determine total community biodiversity-a function of both the total number of
      species present (richness) and their relative distribution (evenness).

PMID- 10966415
TI  - Overexpression of protein disulfide isomerase DsbC stabilizes multiple-disulfide
      bonded recombinant protein produced and transported to the periplasm in
      Escherichia coli.
AB  - Dsb proteins (DsbA, DsbB, DsbC, and DsbD) catalyze formation and isomerization of
      protein disulfide bonds in the periplasm of Escherichia coli. By using a set of
      Dsb coexpression plasmids constructed recently, we analyzed the effects of Dsb
      overexpression on production of horseradish peroxidase (HRP) isozyme C that
      contains complex disulfide bonds and tends to aggregate when produced in E. coli.
      When transported to the periplasm, HRP was unstable but was markedly stabilized
      upon simultaneous overexpression of the set of Dsb proteins (DsbABCD). Whereas
      total HRP production increased severalfold upon overexpression of at least
      disulfide-bonded isomerase DsbC, maximum transport of HRP to the periplasm seemed
      to require overexpression of all DsbABCD proteins, suggesting that excess Dsb
      proteins exert synergistic effects in assisting folding and transport of HRP.
      Periplasmic production of HRP also increased when calcium, thought to play an
      essential role in folding of nascent HRP polypeptide, was added to the medium
      with or without Dsb overexpression. These results suggest that Dsb proteins and
      calcium play distinct roles in periplasmic production of HRP, presumably through
      facilitating correct folding. The present Dsb expression plasmids should be
      useful in assessing and dissecting periplasmic production of proteins that
      contain multiple disulfide bonds in E. coli.

PMID- 10966416
TI  - Effects of high pressure on survival and metabolic activity of Lactobacillus
      plantarum TMW1.460.
AB  - The application of high pressure (HP) for food preservation requires insight into
      mechanisms of HP-mediated cell injury and death. The HP inactivation in model
      beer of Lactobacillus plantarum TMW1.460, a beer-spoiling organism, was
      investigated at pressures ranging from 200 to 600 MPa. Surviving cells were
      characterized by determination of (i) cell viability and sublethal injury, (ii)
      membrane permeability to the fluorescent dyes propidium iodide (PI) and ethidium
      bromide (EB), (iii) metabolic activity with tetrazolium salts, and (iv) the
      activity of HorA, an ATP binding cassette-type multidrug resistance transporter
      conferring resistance to hop compounds. HP inactivation curves exhibited a
      shoulder, an exponential inactivation phase, and pronounced tailing caused by a
      barotolerant fraction of the population, about 1 in 10(6) cells. During
      exponential inactivation, more than 99.99% of cells were sublethally injured;
      however, no sublethal injury was detected in the barotolerant fraction of the
      culture. Sublethally injured cells were metabolically active, and loss of
      metabolic activity corresponded to the decrease of cell viability. Membrane
      damage measured by PI uptake occurred later than cell death, indicating that dye
      exclusion may be used as a fail-safe method for preliminary characterization of
      HP inactivation. An increase of membrane permeability to EB and a reduction of
      HorA activity were observed prior to the loss of cell viability, indicating loss
      of hop resistance of pressurized cells. Even mild HP treatments thus abolished
      the ability of cells to survive under adverse conditions.

PMID- 10966417
TI  - Dissolution of xylose metabolism in Lactococcus lactis.
AB  - Xylose metabolism, a variable phenotype in strains of Lactococcus lactis, was
      studied and evidence was obtained for the accumulation of mutations that
      inactivate the xyl operon. The xylose metabolism operon (xylRAB) was sequenced
      from three strains of lactococci. Fragments of 4.2, 4.2, and 5.4 kb that included
      the xyl locus were sequenced from L. lactis subsp. lactis B-4449 (formerly
      Lactobacillus xylosus), L. lactis subsp. lactis IO-1, and L. lactis subsp. lactis
      210, respectively. The two environmental isolates, L. lactis B-4449 and L. lactis
      IO-1, produce active xylose isomerases and xylulokinases and can metabolize
      xylose. L. lactis 210, a dairy starter culture strain, has neither xylose
      isomerase nor xylulokinase activity and is Xyl(-). Xylose isomerase and
      xylulokinase activities are induced by xylose and repressed by glucose in the two
      Xyl(+) strains. Sequence comparisons revealed a number of point mutations in the
      xylA, xylB, and xylR genes in L. lactis 210, IO-1, and B-4449. None of these
      mutations, with the exception of a premature stop codon in xylB, are obviously
      lethal, since they lie outside of regions recognized as critical for activity.
      Nevertheless, either cumulatively or because of indirect affects on the
      structures of catalytic sites, these mutations render some strains of L. lactis
      unable to metabolize xylose.

PMID- 10966418
TI  - Characteristics of Vibrio parahaemolyticus O3:K6 from Asia.
AB  - A variety of serovars of the food-borne pathogen Vibrio parahaemolyticus normally
      cause infection. Since 1996, the O3:K6 strains of this pathogen have caused
      pandemics in many Asian countries, including Taiwan. For a better understanding
      of these pandemic strains, the recently isolated clinical O3:K6 strains from
      India, Japan, Korea, and Taiwan were examined in terms of pulsed-field gel
      electrophoresis (PFGE) typing and other biological characteristics. After PFGE
      and cluster analysis, all the O3:K6 strains were grouped into two unrelated
      groups. The recently isolated O3:K6 strains were all in one group, consisting of
      eight closely related patterns, with I1(81%) and I5(13%) being the most frequent
      patterns. Pattern I1 was the major one for strains from Japan, Korea, and Taiwan.
      All recently isolated O3:K6 strains carried the thermostable direct hemolysin
      (tdh) gene. No significant difference was observed between recently isolated
      O3:K6 strains and either non-O3:K6 reference strains or old O3:K6 strains
      isolated before 1996 with respect to antibiotic susceptibility, the level of
      thermostable direct hemolysin, and the susceptibility to environmental stresses.
      Results in this study confirmed that the recently isolated O3:K6 strains of V.
      parahaemolyticus are genetically close to each other, while the other biological
      traits examined were usually strain dependent, and no unique trait was found in
      the recently isolated O3:K6 strains.

PMID- 10966419
TI  - Genotypic characterization of Bradyrhizobium strains nodulating small Senegalese
      legumes by 16S-23S rRNA intergenic gene spacers and amplified fragment length
      polymorphism fingerprint analyses.
AB  - We examined the genotypic diversity of 64 Bradyrhizobium strains isolated from
      nodules from 27 native leguminous plant species in Senegal (West Africa)
      belonging to the genera Abrus, Alysicarpus, Bryaspis, Chamaecrista, Cassia,
      Crotalaria, Desmodium, Eriosema, Indigofera, Moghania, Rhynchosia, Sesbania,
      Tephrosia, and Zornia, which play an ecological role and have agronomic potential
      in arid regions. The strains were characterized by intergenic spacer (between 16S
      and 23S rRNA genes) PCR and restriction fragment length polymorphism (IGS PCR
      RFLP) and amplified fragment length polymorphism (AFLP) fingerprinting analyses.
      Fifty-three reference strains of the different Bradyrhizobium species and
      described groups were included for comparison. The strains were diverse and
      formed 27 groups by AFLP and 16 groups by IGS PCR-RFLP. The sizes of the IGS PCR
      products from the Bradyrhizobium strains that were studied varied from 780 to
      1,038 bp and were correlated with the IGS PCR-RFLP results. The grouping of
      strains was consistent by the three methods AFLP, IGS PCR-RFLP, and previously
      reported 16S amplified ribosomal DNA restriction analysis. For investigating the
      whole genome, AFLP was the most discriminative technique, thus being of
      particular interest for future taxonomic studies in Bradyrhizobium, for which DNA
      is difficult to obtain in quantity and quality to perform extensive DNA:DNA
      hybridizations.

PMID- 10966420
TI  - Response of a soil bacterial community to grassland succession as monitored by
      16S rRNA levels of the predominant ribotypes.
AB  - The composition of predominant soil bacteria during grassland succession was
      investigated in the Dutch Drentse A area. Five meadows, taken out of agricultural
      production at different time points, and one currently fertilized plot
      represented different stages of grassland succession. Since fertilization and
      agricultural production were stopped, the six plots showed a constant decline in
      the levels of nutrients and vegetation changes. The activity of the predominant
      bacteria was monitored by direct ribosome isolation from soil and temperature
      gradient gel electrophoresis of reverse transcription (RT)-PCR products generated
      from bacterial 16S rRNA. The amounts of 16S rRNA of 20 predominant ribosome types
      per gram of soil were monitored via multiple competitive RT-PCR in six plots at
      different succession stages. These ribosome types mainly represented Bacillus and
      members of the Acidobacterium cluster and the alpha subclass of the class
      Proteobacteria. The 20 16S rRNA molecules monitored represented approximately
      half of all bacterial soil rRNA which was estimated by dot blot hybridizations of
      soil rRNA with the Bacteria probe EUB338. The grasslands showed highly
      reproducible and specific shifts of bacterial ribosome type composition. The
      total bacterial ribosome level increased during the first years after
      agricultural production and fertilization stopped. This correlated with the
      collapse of the dominant Lolium perenne population and an increased rate of
      mineralization of organic matter. The results indicate that there is a true
      correlation between the total activity of the bacterial community in soil and the
      amount of bacterial ribosomes.

PMID- 10966421
TI  - Application of sequence-specific labeled 16S rRNA gene oligonucleotide probes for
      genetic profiling of cyanobacterial abundance and diversity by array
      hybridization.
AB  - DNA sequence information for the small-subunit rRNA gene (16S rDNA) obtained from
      cyanobacterial cultures was used to investigate the presence of cyanobacteria and
      their abundance in natural habitats. Eight planktonic communities developing in
      lakes characterized by relatively low algal biomass (mesotrophic) and in lakes
      with correspondingly high biomass (eutrophic) were selected for the study. The
      organismal compositions of the water samples were analyzed genetically, using
      multiplex sequence-specific labeling of oligonucleotide probes targeted to 16S
      rDNA and subsequent hybridization of the labeled probes to their respective
      complements spotted onto a solid support (DNA array). Ten probes were established
      to determine the relative abundances of the discernible cyanobacteria encountered
      in the selected lakes. The probes were generally specific for their targets, as
      determined through analyses of clone cultures. Reproducible abundance profiles
      were established for the lakes investigated in the subsequent analyses of natural
      cyanobacterial communities. The results from the genetic analyses were then
      compared with information obtained from standard hydrobiological and
      hydrochemical analyses. Qualitatively, there were relatively good correlations
      among the groups of organisms (Nostoc, Microcystis, and Planktothrix species)
      found in the different lakes. The levels of correlation were lower for the
      quantitative data. This may, however, be due to differences in sample processing
      technique. The conclusions from these comparisons are that the genetic abundance
      profiles may provide a foundation for separating and quantifying genetically
      distinct groups of cyanobacteria in their natural habitats.

PMID- 10966422
TI  - Role of respiratory nitrate reductase in ability of Pseudomonas fluorescens YT101
      to colonize the rhizosphere of maize.
AB  - Selection of the denitrifying community by plant roots (i.e., increase in the
      denitrifier/total heterotroph ratio in the rhizosphere) has been reported by
      several authors. However, very few studies to evaluate the role of the
      denitrifying function itself in the selection of microorganisms in the
      rhizosphere have been performed. In the present study, we compared the
      rhizosphere survival of the denitrifying Pseudomonas fluorescens YT101 strain
      with that of its isogenic mutant deficient in the ability to synthesize the
      respiratory nitrate reductase, coinoculated in nonplanted or planted soil. We
      demonstrated that under nonlimiting nitrate conditions, the denitrifying wild
      type strain had an advantage in the ability to colonize the rhizosphere of maize.
      Investigations of the effect of the inoculum characteristics (density of the
      total inoculum and relative proportions of mutant and wild-type strains) on the
      outcome of the selection demonstrated that the selective effect of the plant was
      expressed only during the phase of bacterial multiplication and that the
      intensity of selection was dependent on the magnitude of this phase. Moreover,
      application of the de Wit replacement series technique to our results suggests
      that the advantage of the wild-type strain was maximal when the ratio between the
      two strains in the inoculum was close to 1:1. This work constitutes the first
      direct demonstration that the presence of a functional structural gene encoding
      the respiratory nitrate reductase confers higher rhizosphere competence to a
      microorganism.

PMID- 10966423
TI  - Exposure of phytopathogenic Xanthomonas spp. to lethal concentrations of multiple
      oxidants affects bacterial survival in a complex manner.
AB  - During plant-microbe interactions and in the environment, Xanthomonas campestris
      pv. phaseoli is likely to be exposed to high concentrations of multiple oxidants.
      Here, we show that simultaneous exposures of the bacteria to multiple oxidants
      affects cell survival in a complex manner. A superoxide generator (menadione)
      enhanced the lethal effect of an organic peroxide (tert-butyl hydroperoxide) by
      1, 000-fold; conversely, treatment of cells with menadione plus H(2)O(2) resulted
      in 100-fold protection compared to that for cells treated with the individual
      oxidants. Treatment of X. campestris with a combination of H(2)O(2) and tert
      butyl hydroperoxide elicited no additive or protective effect. High levels of
      catalase alone are sufficient to protect cells against the lethal effect of
      menadione plus H(2)O(2) and tert-butyl hydroperoxide plus H(2)O(2). These data
      suggest that H(2)O(2) is the lethal agent responsible for killing the bacteria as
      a result of these treatments. However, increased expression of individual genes
      for peroxide (alkyl hydroperoxide reductase, catalase)- and superoxide
      (superoxide dismutase)-scavenging enzymes or concerted induction of oxidative
      stress-protective genes by menadione gave no protection against killing by a
      combination of menadione plus tert-butyl hydroperoxide. However, X. campestris
      cells in the stationary phase and a spontaneous H(2)O(2)-resistant mutant (X.
      campestris pv. phaseoli HR) were more resistant to killing by menadione plus tert
      butyl hydroperoxide. These findings give new insight into oxidant killing of
      Xanthomonas spp. that could be generally applied to other bacteria.

PMID- 10966424
TI  - Virulence genes in environmental strains of Vibrio cholerae.
AB  - The virulence of a pathogen is dependent on a discrete set of genetic
      determinants and their well-regulated expression. The ctxAB and tcpA genes are
      known to play a cardinal role in maintaining virulence in Vibrio cholerae, and
      these genes are believed to be exclusively associated with clinical strains of O1
      and O139 serogroups. In this study, we examined the presence of five virulence
      genes, including ctxAB and tcpA, as well as toxR and toxT, which are involved in
      the regulation of virulence, in environmental strains of V. cholerae cultured
      from three different freshwater lakes and ponds in the eastern part of Calcutta,
      India. PCR analysis revealed the presence of these virulence genes or their
      homologues among diverse serotypes and ribotypes of environmental V. cholerae
      strains. Sequencing of a part of the tcpA gene carried by an environmental strain
      showed 97.7% homology to the tcpA gene of the classical biotype of V. cholerae
      O1. Strains carrying the tcpA gene expressed the toxin-coregulated pilus (TCP),
      demonstrated by both autoagglutination analysis and electron microscopy of the
      TCP pili. Strains carrying ctxAB genes also produced cholera toxin, determined by
      monosialoganglioside enzyme-linked immunosorbent assay and by passage in the
      ileal loops of rabbits. Thus, this study demonstrates the presence and expression
      of critical virulence genes or their homologues in diverse environmental strains
      of V. cholerae, which appear to constitute an environmental reservoir of
      virulence genes, thereby providing new insights into the ecology of V. cholerae.

PMID- 10966425
TI  - Application of the 5'-nuclease PCR assay in evaluation and development of methods
      for quantitative detection of Campylobacter jejuni.
AB  - Campylobacter jejuni is recognized as a leading human food-borne pathogen.
      Traditional diagnostic testing for C. jejuni is not reliable due to special
      growth requirements and the possibility that this bacterium can enter a viable
      but nonculturable state. Nucleic acid-based tests have emerged as a useful
      alternative to traditional enrichment testing. In this article, we present a 5'
      nuclease PCR assay for quantitative detection of C. jejuni and describe its
      evaluation. A probe including positions 381121 to 381206 of the published C.
      jejuni strain NCTC 11168 genome sequence was identified. When this probe was
      applied, the assay was positive for all of the isolates of C. jejuni tested (32
      isolates, including the type strain) and negative for all other Campylobacter
      spp. (11 species tested) and several other bacteria (41 species tested). The
      total assay could be completed in 3 h with a detection limit of approximately 1
      CFU. Quantification was linear over at least 6 log units. Quantitative detection
      methods are important for both research purposes and further development of C.
      jejuni detection methods. In this study, we used the assay to investigate to what
      extent the PCR signals generated by heat-killed bacteria interfere with the
      detection of viable C. jejuni after exposure at elevated temperatures for up to 5
      days. An approach to the reduction of the PCR signal generated by dead bacteria
      was also investigated by employing externally added DNases to selectively
      inactivate free DNA and exposed DNA in heat-killed bacteria. The results
      indicated relatively good discrimination between exposed DNA from dead C. jejuni
      and protected DNA in living bacteria.

PMID- 10966426
TI  - Effect of oxygen on formation and structure of Azotobacter vinelandii alginate
      and its role in protecting nitrogenase.
AB  - The activity of nitrogenase in the nitrogen-fixing bacterium Azotobacter
      vinelandii grown diazotrophically under aerobic conditions is generally
      considered to be protected against O(2) by a high respiration rate. In this work,
      we have shown that a high rate of respiration is not the prevailing mechanism for
      nitrogenase protection in A. vinelandii grown in phosphate-limited nitrogen-free
      chemostat culture. Instead, the formation of alginate appeared to play a decisive
      role in protecting the nitrogenase that is required for cell growth in this
      culture. Depending on the O(2) tension and cell growth rate, the formation rate
      and composition of alginate released into the culture broth varied significantly.
      Furthermore, transmission electron microscopic analysis of cell morphology and
      the cell surface revealed the existence of an alginate capsule on the surface of
      A. vinelandii. The composition, thickness, and compactness of this alginate
      capsule also varied significantly. In general, increasing O(2) tension led to the
      formation of alginate with a higher molecular weight and a greater L-guluronic
      acid content. The alginate capsule was accordingly thicker and more compact. In
      addition, the formation of the alginate capsule was found to be strongly affected
      by the shear rate in a bioreactor. Based on these experimental results, it is
      suggested that the production of alginate, especially the formation of an
      alginate capsule on the cell surface, forms an effective barrier for O(2)
      transfer into the cell. It is obviously the quality, not the quantity, of
      alginate that is decisive for the protection of nitrogenase.

PMID- 10966427
TI  - Characterization of growth and acid formation in a Bacillus subtilis pyruvate
      kinase mutant.
AB  - Based on measurements and theoretical analyses, we identified deletion of
      pyruvate kinase (PYK) activity as a possible route for elimination of acid
      formation in Bacillus subtilis cultures grown on glucose minimal media. Evidence
      consistent with the attenuation of PYK flux has come from metabolic flux
      calculations, metabolic pool and enzymatic activity measurements, and a series of
      nuclear magnetic resonance experiments, all suggesting a nearly complete
      inhibition of PYK activity for glucose-citrate fed cultures in which the amount
      of acid formation was nearly zero. In this paper, we report the construction and
      characterization of a pyk mutant of B. subtilis. Our results demonstrate an
      almost complete elimination of acid production in cultures of the pyk mutant in
      glucose minimal medium. The substantial reduction in acid production is
      accompanied by increased CO(2) production and a reduced rate of growth. Metabolic
      analysis indicated a dramatic increase in intracellular pools of
      phosphoenolpyruvate (PEP) and glucose-6-P in the pyk mutant. The high
      concentrations of PEP and glucose-6-P could explain the decreased growth rate of
      the mutant. The substantial accumulation of PEP does not occur in Escherichia
      coli pyk mutants. The very high concentration of PEP which accumulates in the B.
      subtilis pyk mutant could be exploited for production of various aromatics.

PMID- 10966428
TI  - Parallel processing of substrate correlates with greater functional stability in
      methanogenic bioreactor communities perturbed by glucose.
AB  - Parallel processing is more stable than serial processing in many areas that
      employ interconnected activities. This hypothesis was tested for microbial
      community function using two quadruplicate sets of methanogenic communities, each
      set having substantially different populations. The two communities were
      maintained at a mean cell residence time of 16 days and a mean glucose loading
      rate of 0.34 g/liter-day in variable-volume reactors. To test stability to
      perturbation, they were subjected to an instantaneous glucose pulse that resulted
      in a 6.8-g/liter reactor concentration. The pattern of accumulated products in
      response to the perturbation was analyzed for various measures of functional
      stability, including resistance, resilience, and reactivity for each product. A
      new stability parameter, "moment of amplification envelope," was used to compare
      the soluble compound stability. These parameters indicated that the communities
      with predominantly parallel substrate processing were functionally more stable in
      response to the perturbation than the communities with predominantly serial
      substrate processing. The data also indicated that there was good replication of
      function under perturbed conditions; the degrees of replication were 0.79 and
      0.83 for the two test communities.

PMID- 10966429
TI  - Flexible community structure correlates with stable community function in
      methanogenic bioreactor communities perturbed by glucose.
AB  - Methanogenic bioreactor communities were used as model ecosystems to evaluate the
      relationship between functional stability and community structure. Replicated
      methanogenic bioreactor communities with two different community structures were
      established. The effect of a substrate loading shock on population dynamics in
      each microbial community was examined by using morphological analysis, small
      subunit (SSU) rRNA oligonucleotide probes, amplified ribosomal DNA (rDNA)
      restriction analysis (ARDRA), and partial sequencing of SSU rDNA clones. One set
      of replicated communities, designated the high-spirochete (HS) set, was
      characterized by good replicability, a high proportion of spiral and short thin
      rod morphotypes, a dominance of spirochete-related SSU rDNA genes, and a high
      percentage of Methanosarcina-related SSU rRNA. The second set of communities,
      designated the low-spirochete (LS) set, was characterized by incomplete
      replicability, higher morphotype diversity dominated by cocci, a predominance of
      Streptococcus-related and deeply branching Spirochaetales-related SSU rDNA genes,
      and a high percentage of Methanosaeta-related SSU rRNA. In the HS communities,
      glucose perturbation caused a dramatic shift in the relative abundance of
      fermentative bacteria, with temporary displacement of spirochete-related
      ribotypes by Eubacterium-related ribotypes, followed by a return to the
      preperturbation community structure. The LS communities were less perturbed, with
      Streptococcus-related organisms remaining prevalent after the glucose shock,
      although changes in the relative abundance of minor members were detected by
      morphotype analysis. A companion paper demonstrates that the more stable LS
      communities were less functionally stable than the HS communities (S. A.
      Hashsham, A. S. Fernandez, S. L. Dollhopf, F. B. Dazzo, R. F. Hickey, J. M.
      Tiedje, and C. S. Criddle, Appl. Environ. Microbiol. 66:4050-4057, 2000).

PMID- 10966430
TI  - Intracellular accumulation of polyphosphate by the yeast Candida humicola G-1 in
      response to acid pH.
AB  - Cells of a newly isolated environmental strain of Candida humicola accumulated 10
      fold more polyphosphate (polyP), during active growth, when grown in complete
      glucose-mineral salts medium at pH 5.5 than when grown at pH 7.5. Neither
      phosphate starvation, nutrient limitation, nor anaerobiosis was required to
      induce polyP formation. An increase in intracellular polyP was accompanied by a
      4.5-fold increase in phosphate uptake from the medium and sixfold-higher levels
      of cellular polyphosphate kinase activity. This novel accumulation of polyP by C.
      humicola G-1 in response to acid pH provides further evidence as to the
      importance of polyP in the physiological adaptation of microbial cells during
      growth and development and in their response to environmental stresses.

PMID- 10966431
TI  - Expression of green fluorescent protein in Streptococcus gordonii DL1 and its use
      as a species-specific marker in coadhesion with Streptococcus oralis 34 in saliva
      conditioned biofilms in vitro.
AB  - Streptococcus gordonii is one of the predominant streptococci in the biofilm
      ecology of the oral cavity. It interacts with other bacteria through receptor
      adhesin complexes formed between cognate molecules on the surfaces of the partner
      cells. To study the spatial organization of S. gordonii DL1 in oral biofilms, we
      used green fluorescent protein (GFP) as a species-specific marker to identify S.
      gordonii in a two-species in vitro oral biofilm flowcell system. To drive
      expression of gfp, we isolated and characterized an endogenous S. gordonii
      promoter, PhppA, which is situated upstream of the chromosomal hppA gene encoding
      an oligopeptide-binding lipoprotein. A chromosomal chloramphenicol
      acetyltransferase (cat) gene fusion with PhppA was constructed and used to
      demonstrate that PhppA was highly active throughout the growth of bacteria in
      batch culture. A promoterless 0.8-kb gfp ('gfp) cassette was PCR amplified from
      pBJ169 and subcloned to replace the cat cassette downstream of the S. gordonii
      derived PhppA in pMH109-HPP, generating pMA1. Subsequently, the PhppA-'gfp
      cassette was PCR amplified from pMA1 and subcloned into pDL277 and pVA838 to
      generate the Escherichia coli-S. gordonii shuttle vectors pMA2 and pMA3,
      respectively. Each vector was transformed into S. gordonii DL1 aerobically to
      ensure GFP expression. Flow cytometric analyses of aerobically grown transformant
      cultures were performed over a 24-h period, and results showed that GFP could be
      successfully expressed in S. gordonii DL1 from PhppA and that S. gordonii DL1
      transformed with the PhppA-'gfp fusion plasmid stably maintained the fluorescent
      phenotype. Fluorescent S. gordonii DL1 transformants were used to elucidate the
      spatial arrangement of S. gordonii DL1 alone in biofilms or with the coadhesion
      partner Streptococcus oralis 34 in two-species biofilms in a saliva-conditioned
      in vitro flowcell system. These results show for the first time that GFP
      expression in oral streptococci can be used as a species-specific marker in model
      oral biofilms.

PMID- 10966432
TI  - Purification and characterization of novel antifungal compounds from the
      sourdough Lactobacillus plantarum strain 21B.
AB  - Sourdough lactic acid bacteria were selected for antifungal activity by a
      conidial germination assay. The 10-fold-concentrated culture filtrate of
      Lactobacillus plantarum 21B grown in wheat flour hydrolysate almost completely
      inhibited Eurotium repens IBT18000, Eurotium rubrum FTDC3228, Penicillium
      corylophilum IBT6978, Penicillium roqueforti IBT18687, Penicillium expansum
      IDM/FS2, Endomyces fibuliger IBT605 and IDM3812, Aspergillus niger FTDC3227 and
      IDM1, Aspergillus flavus FTDC3226, Monilia sitophila IDM/FS5, and Fusarium
      graminearum IDM623. The nonconcentrated culture filtrate of L. plantarum 21B
      grown in whole wheat flour hydrolysate had similar inhibitory activity. The
      activity was fungicidal. Calcium propionate at 3 mg ml(-1) was not effective
      under the same assay conditions, while sodium benzoate caused inhibition similar
      to L. plantarum 21B. After extraction with ethyl acetate, preparative silica gel
      thin-layer chromatography, and chromatographic and spectroscopic analyses, novel
      antifungal compounds such as phenyllactic and 4-hydroxy-phenyllactic acids were
      identified in the culture filtrate of L. plantarum 21B. Phenyllactic acid was
      contained at the highest concentration in the bacterial culture filtrate and had
      the highest activity. It inhibited all the fungi tested at a concentration of 50
      mg ml(-1) except for P. roqueforti IBT18687 and P. corylophilum IBT6978
      (inhibitory concentration, 166 mg ml(-1)). L. plantarum 20B, which showed high
      antimold activity, was also selected. Preliminary studies showed that
      phenyllactic and 4-hydroxy-phenyllactic acids were also contained in the
      bacterial culture filtrate of strain 20B. Growth of A. niger FTDC3227 occurred
      after 2 days in breads started with Saccharomyces cerevisiae 141 alone or with S.
      cerevisiae and Lactobacillus brevis 1D, an unselected but acidifying lactic acid
      bacterium, while the onset of fungal growth was delayed for 7 days in bread
      started with S. cerevisiae and selected L. plantarum 21B.

PMID- 10966433
TI  - Alterations in the proteome of the Euprymna scolopes light organ in response to
      symbiotic Vibrio fischeri.
AB  - During the onset of the cooperative association between the Hawaiian sepiolid
      squid Euprymna scolopes and the marine luminous bacterium Vibrio fischeri, the
      anatomy and morphology of the host's symbiotic organ undergo dramatic changes
      that require interaction with the bacteria. This morphogenetic process involves
      an array of tissues, including those in direct contact with, as well as those
      remote from, the symbiotic bacteria. The bacteria induce the developmental
      program soon after colonization of the organ, although complete morphogenesis
      requires 96 h. In this study, to determine critical time points, we examined the
      biochemistry underlying bacterium-induced host development using two-dimensional
      polyacrylamide gel electrophoresis. Specifically, V. fischeri-induced changes in
      the soluble proteome of the symbiotic organ during the first 96 h of symbiosis
      were identified by comparing the protein profiles of symbiont-colonized and
      uncolonized organs. Both symbiosis-related changes and age-related changes were
      analyzed to determine what proportion of the differences in the proteomes was the
      result of specific responses to interaction with bacteria. Although no
      differences were detected over the first 24 h, numerous symbiosis-related changes
      became apparent at 48 and 96 h and were more abundant than age-related changes.
      In addition, many age-related protein changes occurred 48 h sooner in symbiotic
      animals, suggesting that the interaction of squid tissue with V. fischeri cells
      accelerates certain developmental processes of the symbiotic organ. These data
      suggest that V. fischeri-induced modifications in host tissues that occur in the
      first 24 h of the symbiosis are independent of marked alterations in the patterns
      of abundant proteins but that the full 4-day morphogenetic program requires
      significant alteration of the host soluble proteome.

PMID- 10966435
TI  - In situ reproductive rate of freshwater Caulobacter spp.
AB  - Electron microscope grids were submerged in Lake Washington, Seattle, Wash., in
      June 1996 as bait to which Caulobacter sp. swarmers would attach and on which
      they would then reproduce in situ. Enumeration of bands in the stalks of attached
      cells implied that the caulobacters were completing approximately three
      reproductive cycles per day. A succession of morphological types of caulobacters
      occurred, as well as an episode of bacteriovore grazing that slowed the
      accumulation of caulobacters and prevented the aging of the population.

PMID- 10966434
TI  - Toluene-degrading bacteria are chemotactic towards the environmental pollutants
      benzene, toluene, and trichloroethylene.
AB  - The bioremediation of polluted groundwater and toxic waste sites requires that
      bacteria come into close physical contact with pollutants. This can be
      accomplished by chemotaxis. Five motile strains of bacteria that use five
      different pathways to degrade toluene were tested for their ability to detect and
      swim towards this pollutant. Three of the five strains (Pseudomonas putida F1,
      Ralstonia pickettii PKO1, and Burkholderia cepacia G4) were attracted to toluene.
      In each case, the response was dependent on induction by growth with toluene.
      Pseudomonas mendocina KR1 and P. putida PaW15 did not show a convincing response.
      The chemotactic responses of P. putida F1 to a variety of toxic aromatic
      hydrocarbons and chlorinated aliphatic compounds were examined. Compounds that
      are growth substrates for P. putida F1, including benzene and ethylbenzene, were
      chemoattractants. P. putida F1 was also attracted to trichloroethylene (TCE),
      which is not a growth substrate but is dechlorinated and detoxified by P. putida
      F1. Mutant strains of P. putida F1 that do not oxidize toluene were attracted to
      toluene, indicating that toluene itself and not a metabolite was the compound
      detected. The two-component response regulator pair TodS and TodT, which control
      expression of the toluene degradation genes in P. putida F1, were required for
      the response. This demonstration that soil bacteria can sense and swim towards
      the toxic compounds toluene, benzene, TCE, and related chemicals suggests that
      the introduction of chemotactic bacteria into selected polluted sites may
      accelerate bioremediation processes.

PMID- 10966436
TI  - Lactococcus lactis as a cell factory for high-level diacetyl production.
AB  - We report the engineering of Lactococcus lactis for the efficient conversion of
      sugar into diacetyl by combining NADH-oxidase overproduction and alpha
      acetolactate decarboxylase inactivation. Eighty percent of the carbon flux was
      found to be rerouted via alpha-acetolactate to the production of diacetyl by
      preloading the cells with NADH-oxidase before their use as a cell factory.

PMID- 10966437
TI  - Quantitative immunocapture PCR assay for detection of Campylobacter jejuni in
      foods.
AB  - The rapid detection of food-borne bacterial pathogens as part of a quality
      control program is necessary for the maintenance of a safe food supply. In this
      report, we present our findings for an immunocapture PCR method for the detection
      of Campylobacter jejuni in foods. The method permits direct detection of the
      pathogen without an enrichment step and can be performed in approximately 8 h.
      Assay results are quantitative, and one cell in a milliliter sample can be
      detected. Application of the method to spiked milk samples and chicken skin
      washes did not affect the sensitivity of the assay.

PMID- 10966438
TI  - Hydrogen peroxide sensitivity of catechol-2,3-dioxygenase: a cautionary note on
      use of xylE reporter fusions under aerobic conditions.
AB  - Catechol-2,3-dioxygenase (C23O) of Pseudomonas putida, encoded by the xylE gene,
      was found to be sensitive to hydrogen peroxide (H(2)O(2)) when used as a reporter
      in gene fusion constructs. Exposure of Pseudomonas aeruginosa katA or katA katB
      mutants harboring katA- or katB-lacZ (encoding beta-galactosidase) or -xylE
      fusion plasmids to H(2)O(2) stimulated beta-galactosidase activity, while there
      was little or no detectable C23O activity in these strains. More than 95% of C23O
      activity was lost after a 5-min exposure to equimolar H(2)O(2), while a 10,000
      fold excess was required for similar inhibition of beta-galactosidase. Electron
      paramagnetic resonance spectra of the nitrosyl complexes of C23O showed that
      H(2)O(2) nearly stoichiometrically oxidized the essential active-site ferrous
      ion, thus accounting for the loss of activity. Our results suggest using caution
      in interpreting data derived from xylE reporter fusions under aerobic conditions,
      especially where oxidative stress is present or when catalase-deficient strains
      are used.

PMID- 10966439
TI  - Murine monoclonal antibodies specific for lipopolysaccharide of Escherichia coli
      O26 and O111.
AB  - Monoclonal antibody (MAb) 12F5 reacted with 35 Escherichia coli O26 isolates and
      cross-reacted with 1 of 365 non-E. coli O26 isolates. MAb 15C4 reacted with 30 E.
      coli O111 strains and 8 Salmonella O35 strains (possessing identical O antigen)
      but not with 362 other bacterial strains. Lipopolysaccharide immunoblots
      confirmed MAb O-antigen specificity.

PMID- 10966440
TI  - Resuscitation by ferrioxamine E of stressed Salmonella enterica serovar
      typhimurium from soil and water microcosms.
AB  - Storage of Salmonella enterica serovar Typhimurium strains in soil and water
      microcosms resulted in loss of culturability on standard plating media. Prior
      incubation in buffered peptone water supplemented with ferrioxamine E markedly
      extended the time that bacteria were recoverable by plating, except in the case
      of mutants deficient in ferrioxamine E uptake.

PMID- 10966441
TI  - Rapid 5' nuclease (TaqMan) assay for detection of virulent strains of Yersinia
      enterocolitica.
AB  - We have developed a rapid procedure for the detection of virulent Yersinia
      enterocolitica in ground pork by combining a previously described PCR with
      fluorescent dye technologies. The detection method, known as the fluorogenic 5'
      nuclease assay (TaqMan), produces results by measuring the fluorescence produced
      during PCR amplification, requiring no post-PCR processing. The specificity of
      the chromosomal yst gene-based assay was tested with 28 bacterial isolates that
      included 7 pathogenic and 7 nonpathogenic serotypes of Y. enterocolitica, other
      species of Yersinia (Y. aldovae, Y. pseudotuberculosis, Y. mollaretti, Y.
      intermedia, Y. bercovieri, Y. ruckeri, Y. frederiksenii, and Y. kristensenii),
      and other enteric bacteria (Escherichia, Salmonella, Citrobacter, and
      Flavobacterium). The assay was 100% specific in identifying the pathogenic
      strains of Y. enterocolitica. The sensitivity of the assay was found to be
      >/=10(2) CFU/ml in pure cultures and >/=10(3) CFU/g in spiked ground pork
      samples. Results of the assay with food enrichments prespiked with Y.
      enterocolitica serotypes O:3 and O:9 were comparable to standard culture results.
      Of the 100 field samples (ground pork) tested, 35 were positive for virulent Y.
      enterocolitica with both 5' nuclease assay and conventional virulence tests.
      After overnight enrichment the entire assay, including DNA extraction,
      amplification, and detection, could be completed within 5 h.

PMID- 10966442
TI  - Starvation alters the apparent half-saturation constant for methane in the type
      II methanotroph Methylocystis strain LR1.
AB  - When cells of a type II methanotrophic bacterium (Methylocystis strain LR1) were
      starved of methane, both the K(m(app)) and the V(max(app)) for methane decreased.
      The specific affinity (a(o)(s)) remained nearly constant. Therefore, the
      decreased K(m(app)) in starved cells was probably not an adjustment to better
      utilize low-methane concentrations.

PMID- 10966443
TI  - Identification and characteristics of a novel Burkholderia strain with broad
      spectrum antimicrobial activity.
AB  - A Burkholderia strain isolated from soil is capable of inhibiting the growth of
      bacteria, plant-pathogenic fungi, pathogenic yeasts, and protozoa. Inhibition
      does not involve cell contact or the presence of living cells, suggesting that at
      least a substantial portion of the antimicrobial activity is due to the excretion
      of extracellular compounds.

PMID- 10966444
TI  - Anhydrobiotic engineering of gram-negative bacteria.
AB  - Anhydrobiotic engineering aims to improve desiccation tolerance in living
      organisms by adopting the strategies of anhydrobiosis. This was achieved for
      Escherichia coli and Pseudomonas putida by osmotic induction of intracellular
      trehalose synthesis and by drying from trehalose solutions, resulting in long
      term viability in the dried state.

PMID- 10966445
TI  - Molecular phylogeny of Anabaena circinalis and its identification in
      environmental samples by PCR.
AB  - Although the cyanobacterium Anabaena circinalis occurs worldwide, Australian
      isolates are believed to exclusively possess the saxitoxin group neurotoxins
      (paralytic shellfish poisons). Identification of A. circinalis in a mixed
      population is complicated due to limited morphological differences between
      Anabaena species. Sequence analysis of the DNA-dependent RNA polymerase (rpoC1)
      gene from 24 Anabaena isolates, including 12 designated A. circinalis, permitted
      a phylogenetic analysis to be performed. In addition, an A. circinalis-specific
      PCR was developed and tested successfully on environmental samples.

PMID- 10966446
TI  - Determination of the sensitivity of a rapid Escherichia coli O157:H7 assay for
      testing 375-gram composite samples.
AB  - Both 25-g single-size ground beef samples and 375-g composite ground beef samples
      were tested by a method combining an immunomagnetic separation (IMS) technique
      with a sandwich enzyme-linked immunosorbent assay (ELISA) system (IMS-ELISA). The
      results demonstrated that IMS-ELISA could detect the target, Escherichia coli
      O157:H7, at the level of 10(-1) CFU/g of sample in either the 25- or 375-g sample
      size.

PMID- 10966447
TI  - Construction of a multihybrid display system: flagellar filaments carrying two
      foreign adhesive peptides.
AB  - A multivalent, bifunctional flagellum carrying two different adhesive peptides in
      separate flagellin subunits within a filament was constructed in Escherichia
      coli. The inserted peptides were the fibronectin-binding 115-mer D repeat region
      of Staphylococcus aureus and the 302-mer collagen-binding region of YadA of
      Yersinia enterocolitica. Western blotting, immunoelectron microscopy, and
      adhesion tests with hybrid flagella from an in trans-complemented DeltafliC E.
      coli strain showed that individual filaments consisted of both recombinant
      flagellins.

PMID- 10966448
TI  - Transformation of triclosan by Trametes versicolor and Pycnoporus cinnabarinus.
AB  - We investigated the ability of Trametes versicolor and Pycnoporous cinnabarinus
      to metabolize triclosan. T. versicolor produced three metabolites, 2-O-(2,4,4'
      trichlorodiphenyl ether)-beta-D-xylopyranoside, 2-O-(2,4,4'-trichlorodiphenyl
      ether)-beta-D-glucopyranoside, and 2,4-dichlorophenol. P. cinnabarinus converted
      triclosan to 2,4, 4'-trichloro-2'-methoxydiphenyl ether and the glucoside
      conjugate known from T. versicolor. The conjugates showed a distinctly lower
      cytotoxic and microbicidal activity than triclosan did.

PMID- 10966449
TI  - Plant genome complexity may be a factor limiting in situ the transfer of
      transgenic plant genes to the phytopathogen Ralstonia solanacearum.
AB  - The development of natural competence by bacteria in situ is considered one of
      the main factors limiting transformation-mediated gene exchanges in the
      environment. Ralstonia solanacearum is a plant pathogen that is also a naturally
      transformable bacterium that can develop the competence state during infection of
      its host. We have attempted to determine whether this bacterium could become the
      recipient of plant genes. We initially demonstrated that plant DNA was released
      close to the infecting bacteria. We constructed and tested various combinations
      of transgenic plants and recipient bacteria to show that the effectiveness of
      such transfers was directly related to the ratio of the complexity of the plant
      genome to the number of copies of the transgene.

PMID- 10966450
TI  - Expression of a tetraheme protein, Desulfovibrio vulgaris Miyazaki F cytochrome
      c(3), in Shewanella oneidensis MR-1.
AB  - Cytochrome c(3) from Desulfovibrio vulgaris Miyazaki F was successfully expressed
      in the facultative aerobe Shewanella oneidensis MR-1 under anaerobic,
      microaerophilic, and aerobic conditions, with yields of 0.3 to 0.5 mg of
      cytochrome/g of cells. A derivative of the broad-host-range plasmid pRK415
      containing the cytochrome c(3) gene from D. vulgaris Miyazaki F was used for
      transformation of S. oneidensis MR-1, resulting in the production of protein
      product that was indistinguishable from that produced by D. vulgaris Miyazaki F,
      except for the presence of one extra alanine residue at the N terminus.

PMID- 10966451
TI  - Still looking for the Ivory Tower.
AB  - Following graduate training, which was disrupted by my changing schools and
      serving in the Navy in World War II, I arrived in Berkeley in 1948 as an
      instructor in the Biochemistry Department. Despite numerous academic
      reorganizations and a host of struggles over the University-imposed Loyalty Oath,
      dismissal of a faculty member because of political affiliations, free speech for
      students, and my resistance to mandatory retirement, I survived with the help of
      great graduate students, postdoctoral fellows, undergraduates, superb research
      assistants, and a supportive wife. Studies on structure of tobacco mosaic virus
      led to our investigating an ultracentrifuge anomaly and the construction of a
      synthetic boundary cell. In turn, this resulted in about 15 years of research on
      the ultracentrifuge and its application to the study of biological
      macromolecules. Among the latter, the discovery of large ribonucleoprotein
      complexes, now known as ribosomes, and chromatophores in photosynthetic
      microorganisms attracted the most attention. But it was the development of the
      photoelectric absorption optical system and the incorporation of the Rayleigh
      interferometer onto the ultracentrifuge that had the greatest impact on our
      further research. These tools, when applied to our initial research on E. coli
      aspartate transcarbamoylase (ATCase), led to the discovery of distinct subunits
      for catalysis and regulation and the global conformational change in the enzyme
      associated with its role in regulation. For almost 35 years we have been using
      the techniques of protein chemistry and molecular biology in studies of
      structural and conformational changes in the enzyme, the genes encoding the
      different polypeptides, subunit interactions, and assembly of the enzyme from six
      catalytic and six regulatory chains. Hybrids constructed from inactive mutants
      were used to demonstrate shared active sites requiring the joint participation of
      amino acid residues from adjoining polypeptide chains. ATCase is still being
      studied as a model for understanding allostery as a regulatory mechanism.
      Circularly permuted polypeptide chains are being used to study the folding and
      assembly pathways, and the recently determined crystal structure of the active
      nonallosteric catalytic subunit has led to new questions regarding the activated
      form of ATCase.

PMID- 10966452
TI  - Cryptochrome: the second photoactive pigment in the eye and its role in circadian
      photoreception.
AB  - Circadian rhythms are oscillations in the biochemical, physiological, and
      behavioral functions of organisms that occur with a periodicity of approximately
      24 h. They are generated by a molecular clock that is synchronized with the solar
      day by environmental photic input. The cryptochromes are the mammalian circadian
      photoreceptors. They absorb light and transmit the electromagnetic signal to the
      molecular clock using a pterin and flavin adenine dinucleotide (FAD) as
      chromophore/cofactors, and are evolutionarily conserved and structurally related
      to the DNA repair enzyme photolyase. Humans and mice have two cryptochrome genes,
      CRY1 and CRY2, that are differentially expressed in the retina relative to the
      opsin-based visual photoreceptors. CRY1 is highly expressed with circadian
      periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus
      (SCN). Mutant mice lacking either Cry1 or Cry2 have impaired light induction of
      the clock gene mPer1 and have abnormally short or long intrinsic periods,
      respectively. The double mutant has normal vision but is defective in mPer1
      induction by light and lacks molecular and behavioral rhythmicity in constant
      darkness. Thus, cryptochromes are photoreceptors and central components of the
      molecular clock. Genetic evidence also shows that cryptochromes are circadian
      photoreceptors in Drosophila and Arabidopsis, raising the possibility that they
      may be universal circadian photoreceptors. Research on cryptochromes may provide
      new understanding of human diseases such as seasonal affective disorder and
      delayed sleep phase syndrome.

PMID- 10966453
TI  - Protein glucosylation and its role in protein folding.
AB  - An unconventional mechanism for retaining improperly folded glycoproteins and
      facilitating acquisition of their native tertiary and quaternary structures
      operates in the endoplasmic reticulum. Recognition of folding glycoproteins by
      two resident lectins, membrane-bound calnexin and its soluble homolog,
      calreticulin, is mediated by protein-linked monoglucosylated oligosaccharides.
      These oligosaccharides contain glucose (Glc), mannose (Man), and N
      acetylglucosamine (GlcNAc) in the general form Glc1Man7-9GlcNAc2. They are formed
      by glucosidase I- and II-catalyzed partial deglucosylation of the oligosaccharide
      transferred from dolichol diphosphate derivatives to Asn residues in nascent
      polypeptide chains (Glc3Man9GlcNAc2). Further deglucosylation of the
      oligosaccharides by glucosidase II liberates glycoproteins from their
      calnexin/calreticulin anchors. Monoglucosylated glycans are then recreated by the
      UDP-Glc:glycoprotein glucosyltransferase (GT), and thus recognized again by the
      lectins, only when linked to improperly folded protein moieties, as GT behaves as
      a sensor of glycoprotein conformations. The deglucosylation-reglucosylation cycle
      continues until proper folding is achieved. The lectin-monoglucosylated
      oligosaccharide interaction is one of the alternative ways by which cells retain
      improperly folded glycoproteins in the endoplasmic reticulum. Although it
      decreases the folding rate, it increases folding efficiency, prevents premature
      glycoprotein oligomerization and degradation, and suppresses formation of non
      native disulfide bonds by hindering aggregation and thus allowing interaction of
      protein moieties of folding glycoproteins with classical chaperones and other
      proteins that assist in folding.

PMID- 10966454
TI  - Spindle assembly in animal cells.
AB  - Chromosome segregation during mitosis and meiosis is driven by a complex
      superstructure called the spindle. Microtubules are the primary structural
      component of spindles, and spindle assembly and function are intimately linked to
      the intrinsic dynamics of microtubules. This review summarizes spindle structure
      and highlights recent findings regarding the mechanisms and molecules involved in
      organizing microtubules into spindles. In addition, mechanisms for chromosome
      movement and segregation are discussed.

PMID- 10966455
TI  - Chromosome cohesion, condensation, and separation.
AB  - The faithful segregation of genetic information requires highly orchestrated
      changes of chromosome structure during the mitotic cell cycle. The linkage
      between duplicated sister DNAs is established during S phase and maintained
      throughout G2 phase (cohesion). In early mitosis, dramatic structural changes
      occur to produce metaphase chromosomes, each consisting of a pair of compacted
      sister chromatids (condensation). At anaphase onset, a signal is produced to
      disrupt the linkage between sister chromatids (separation), allowing them to be
      pulled apart to opposite poles of the cell. This review discusses our current
      understanding of the three stages of large-scale structural changes of
      chromosomes in eukaryotic cells. Recent genetic and biochemical studies have
      identified key components involved in these processes and started to uncover
      hitherto unexpected functional links between mitotic chromosome dynamics and
      other important chromosome functions.

PMID- 10966456
TI  - Cyclooxygenases: structural, cellular, and molecular biology.
AB  - The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also
      cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in
      prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are
      the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including
      aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with
      NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these
      drugs reduces fatal thrombotic events, as well as the development of colon cancer
      and Alzheimer's disease. In this review, we examine how the structures of these
      enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and
      how differences in the structure of PGHS-2 confer on this isozyme differential
      sensitivity to COX-2 inhibitors. We further examine the evidence for independent
      signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS
      2 gene expression.

PMID- 10966457
TI  - Two-component signal transduction.
AB  - Most prokaryotic signal-transduction systems and a few eukaryotic pathways use
      phosphotransfer schemes involving two conserved components, a histidine protein
      kinase and a response regulator protein. The histidine protein kinase, which is
      regulated by environmental stimuli, autophosphorylates at a histidine residue,
      creating a high-energy phosphoryl group that is subsequently transferred to an
      aspartate residue in the response regulator protein. Phosphorylation induces a
      conformational change in the regulatory domain that results in activation of an
      associated domain that effects the response. The basic scheme is highly
      adaptable, and numerous variations have provided optimization within specific
      signaling systems. The domains of two-component proteins are modular and can be
      integrated into proteins and pathways in a variety of ways, but the core
      structures and activities are maintained. Thus detailed analyses of a relatively
      small number of representative proteins provide a foundation for understanding
      this large family of signaling proteins.

PMID- 10966458
TI  - Apoptosis signaling.
AB  - Apoptosis, a physiological process for killing cells, is critical for the normal
      development and function of multicellular organisms. Abnormalities in cell death
      control can contribute to a variety of diseases, including cancer, autoimmunity,
      and degenerative disorders. Signaling for apoptosis occurs through multiple
      independent pathways that are initiated either from triggering events within the
      cell or from outside the cell, for instance, by ligation of death receptors. All
      apoptosis signaling pathways converge on a common machinery of cell destruction
      that is activated by a family of cysteine proteases (caspases) that cleave
      proteins at aspartate residues. Dismantling and removal of doomed cells is
      accomplished by proteolysis of vital cellular constituents, DNA degradation, and
      phagocytosis by neighboring cells. This article reviews current knowledge of
      apoptosis signaling, lists several pressing questions, and presents a novel model
      to explain the biochemical and functional interactions between components of the
      cell death regulatory machinery.

PMID- 10966459
TI  - Yeast homotypic vacuole fusion: a window on organelle trafficking mechanisms.
AB  - Homotypic (self) fusion of yeast vacuoles, which is essential for the low copy
      number of this organelle, uses catalytic elements similar to those used in
      heterotypic vesicular trafficking reactions between different organelles
      throughout nature. The study of vacuole inheritance has benefited from the ease
      of vacuole isolation, the availability of the yeast genome sequence and numerous
      mutants, and from a rapid, quantitative in vitro assay of fusion. The soluble
      proteins and small molecules that support fusion are being defined, conserved
      membrane proteins that catalyze the reaction have been identified, and the
      vacuole membrane has been solubilized and reconstituted into fusion-competent
      proteoliposomes, allowing the eventual purification of all needed factors.
      Studies of homotypic vacuole fusion have suggested a modified paradigm of
      membrane fusion in which integral membrane proteins termed "SNAREs" can form
      stable complexes in cis (when on the same membrane) as well as in trans (when
      anchored to opposing membranes). Chaperones (NSF/Sec18p, LMA1, and -SNAP/Sec17p)
      disassemble cis-SNARE complexes to prepare for the docking of organelles rather
      than to drive fusion. The specificity of organelle docking resides in a cascade
      of trans-interactions (involving Rab-like GTPases), "tethering factors," and
      trans-SNARE pairing. Fusion itself, the mixing of the membrane bilayers and the
      organelle contents, is triggered by calcium signaling.

PMID- 10966460
TI  - Structural insights into microtubule function.
AB  - Microtubules are polymers that are essential for, among other functions, cell
      transport and cell division in all eukaryotes. The regulation of the microtubule
      system includes transcription of different tubulin isotypes, folding of /?
      tubulin heterodimers, post-translation modification of tubulin, and nucleotide
      based microtubule dynamics, as well as interaction with numerous microtubule
      associated proteins that are themselves regulated. The result is the precise
      temporal and spatial pattern of microtubules that is observed throughout the cell
      cycle. The recent high-resolution analysis of the structure of tubulin and the
      microtubule has brought new insight to the study of microtubule function and
      regulation, as well as the mode of action of antimitotic drugs that disrupt
      normal microtubule behavior. The combination of structural, genetic, biochemical,
      and biophysical data should soon give us a fuller understanding of the exquisite
      details in the regulation of the microtubule cytoskeleton.

PMID- 10966461
TI  - Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and
      mammalian cells.
AB  - The sequestration and delivery of cytoplasmic material to the yeast vacuole and
      mammalian lysosome require the dynamic mobilization of cellular membranes and
      specialized protein machinery. Under nutrient deprivation conditions, double
      membrane vesicles form around bulk cytoplasmic cargo destined for degradation and
      recycling in the vacuole/lysosome. A similar process functions to remove excess
      organelles under vegetative conditions in which they are no longer needed.
      Biochemical, morphological, and molecular genetic studies in yeasts and mammalian
      cells have begun to elucidate the molecular details of this autophagy process. In
      addition, the overlap of macroautophagy with the process of pexophagy and with
      the biosynthetic cytoplasm-to-vacuole targeting pathway, which delivers the
      resident vacuolar hydrolase aminopeptidase I, indicates that these three pathways
      are related mechanistically. Identification and characterization of the
      autophagic/cytoplasm-to-vacuole protein-targeting components have revealed the
      essential roles for various functional classes of proteins, including a novel
      protein conjugation system and the machinery for vesicle formation and fusion.

PMID- 10966462
TI  - Coupling of open reading frames by translational bypassing.
AB  - Translational bypassing joins the information found within two disparate open
      reading frames into a single polypeptide chain. The underlying mechanism centers
      on the decoding properties of peptidyl-transfer RNA (tRNA) and involves three
      stages: take-off, scanning, and landing. In take-off, the peptidyl-tRNA/messenger
      RNA (mRNA) complex in the P site of the ribosome dissociates, and the mRNA begins
      to move through the ribosome. In scanning, the peptidyl-tRNA probes the mRNA
      sliding through the decoding center. In landing, the peptidyl-tRNA re-pairs with
      a codon with which it can form a stable interaction. Although few examples of
      genes are known that rely on translational bypassing to couple open reading
      frames, ribosomes appear to have an innate capacity for bypassing. This suggests
      that the strategy of translational bypassing may be more common than presently
      appreciated. The best characterized example of this phenomenon is T4 gene 60, in
      which a complex set of signals stimulates bypassing of 50 nucleotides between the
      two open reading frames. In this review, we focus on the bypassing mechanism of
      gene 60 in terms of take-off, scanning, and landing.

PMID- 10966463
TI  - Protein tyrosine kinase structure and function.
AB  - Tyrosine phosphorylation is one of the key covalent modifications that occurs in
      multicellular organisms as a result of intercellular communication during
      embryogenesis and maintenance of adult tissues. The enzymes that carry out this
      modification are the protein tyrosine kinases (PTKs), which catalyze the transfer
      of the phosphate of ATP to tyrosine residues on protein substrates.
      Phosphorylation of tyrosine residues modulates enzymatic activity and creates
      binding sites for the recruitment of downstream signaling proteins. Two classes
      of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor
      PTKs. Because PTKs are critical components of cellular signaling pathways, their
      catalytic activity is strictly regulated. Over the past several years, high
      resolution structural studies of PTKs have provided a molecular basis for
      understanding the mechanisms by which receptor and nonreceptor PTKs are
      regulated. This review will highlight the important results that have emerged
      from these structural studies.

PMID- 10966464
TI  - Import of peroxisomal matrix and membrane proteins.
AB  - This review summarizes the progress made in our understanding of peroxisome
      biogenesis in the last few years, during which the functional roles of many of
      the 23 peroxins (proteins involved in peroxisomal protein import and peroxisome
      biogenesis) have become clearer. Previous reviews in the field have focussed on
      the metabolic functions of peroxisomes, aspects of import/biogenesis the role of
      peroxins in human disease, and involvement of the endoplasmic reticulum in
      peroxisome membrane biogenesis as well as the degradation of this organelle. This
      review refers to some of the earlier work for the sake of introduction and
      continuity but deals primarily with the more recent progress. The principal areas
      of progress are the identification of new peroxins, definition of protein-protein
      interactions among peroxins leading to the recognition of complexes involved in
      peroxisomal protein import, insight into the biogenesis of peroxisomal membrane
      proteins, and, of most importance, the elucidation of the role of many conserved
      peroxins in human disease. Given the rapid progress in the field, this review
      also highlights some of the unanswered questions that remain to be tackled.

PMID- 10966465
TI  - Platelet-activating factor and related lipid mediators.
AB  - Platelet-activating factor (PAF) is a phospholipid with potent, diverse
      physiological actions, particularly as a mediator of inflammation. The synthesis,
      transport, and degradation of PAF are tightly regulated, and the biochemical
      basis for many of these processes has been elucidated in recent years. Many of
      the actions of PAF can be mimicked by structurally related phospholipids that are
      derived from nonenzymatic oxidation, because such compounds can bind to the PAF
      receptor. This process circumvents much of the biochemical control and presumably
      is regulated primarily by the rate of degradation, which is catalyzed by PAF
      acetylhydrolase. The isolation of cDNA clones encoding most of the key proteins
      involved in regulating PAF has allowed substantial recent progress and will
      facilitate studies to determine the structural basis for substrate specificity
      and the precise role of PAF in physiological events.

PMID- 10966466
TI  - Protein splicing and related forms of protein autoprocessing.
AB  - Protein splicing is a form of posttranslational processing that consists of the
      excision of an intervening polypeptide sequence, the intein, from a protein,
      accompanied by the concomitant joining of the flanking polypeptide sequences, the
      exteins, by a peptide bond. It requires neither cofactors nor auxiliary enzymes
      and involves a series of four intramolecular reactions, the first three of which
      occur at a single catalytic center of the intein. Protein splicing can be
      modulated by mutation and converted to highly specific self-cleavage and protein
      ligation reactions that are useful protein engineering tools. Some of the
      reactions characteristic of protein splicing also occur in other forms of protein
      autoprocessing, ranging from peptide bond cleavage to conjugation with nonprotein
      moieties. These mechanistic similarities may be the result of convergent
      evolution, but in at least one case-hedgehog protein autoprocessing-there is
      definitely a close evolutionary relationship to protein splicing.

PMID- 10966467
TI  - DNA replication fidelity.
AB  - DNA replication fidelity is a key determinant of genome stability and is central
      to the evolution of species and to the origins of human diseases. Here we review
      our current understanding of replication fidelity, with emphasis on structural
      and biochemical studies of DNA polymerases that provide new insights into the
      importance of hydrogen bonding, base pair geometry, and substrate-induced
      conformational changes to fidelity. These studies also reveal polymerase
      interactions with the DNA minor groove at and upstream of the active site that
      influence nucleotide selectivity, the efficiency of exonucleolytic proofreading,
      and the rate of forming errors via strand misalignments. We highlight common
      features that are relevant to the fidelity of any DNA synthesis reaction, and
      consider why fidelity varies depending on the enzymes, the error, and the local
      sequence environment.

PMID- 10966468
TI  - Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin.
AB  - Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of
      influenza virus and the target for infectivity-neutralizing antibodies. The
      structures of three conformations of the ectodomain of the 1968 Hong Kong
      influenza virus HA have been determined by X-ray crystallography: the single
      chain precursor, HA0; the metastable neutral-pH conformation found on virus, and
      the fusion pH-induced conformation. These structures provide a framework for
      designing and interpreting the results of experiments on the activity of HA in
      receptor binding, the generation of emerging and reemerging epidemics, and
      membrane fusion during viral entry. Structures of HA in complex with sialic acid
      receptor analogs, together with binding experiments, provide details of these low
      affinity interactions in terms of the sialic acid substituents recognized and the
      HA residues involved in recognition. Neutralizing antibody-binding sites surround
      the receptor-binding pocket on the membrane-distal surface of HA, and the
      structures of the complexes between neutralizing monoclonal Fabs and HA indicate
      possible neutralization mechanisms. Cleavage of the biosynthetic precursor HA0 at
      a prominent loop in its structure primes HA for subsequent activation of membrane
      fusion at endosomal pH (Figure 1). Priming involves insertion of the fusion
      peptide into a charged pocket in the precursor; activation requires its extrusion
      towards the fusion target membrane, as the N terminus of a newly formed trimeric
      coiled coil, and repositioning of the C-terminal membrane anchor near the fusion
      peptide at the same end of a rod-shaped molecule. Comparison of this new HA
      conformation, which has been formed for membrane fusion, with the structures
      determined for other virus fusion glycoproteins suggests that these molecules are
      all in the fusion-activated conformation and that the juxtaposition of the
      membrane anchor and fusion peptide, a recurring feature, is involved in the
      fusion mechanism. Extension of these comparisons to the soluble N-ethyl-maleimide
      sensitive factor attachment protein receptor (SNARE) protein complex of vesicle
      fusion allows a similar conclusion.

PMID- 10966469
TI  - Mechanisms and control of mRNA decapping in Saccharomyces cerevisiae.
AB  - The process of mRNA turnover is a critical component of the regulation of gene
      expression. In the past few years a discrete set of pathways for the degradation
      of polyadenylated mRNAs in eukaryotic cells have been described. A major pathway
      of mRNA degradation in yeast occurs by deadenylation of the mRNA, which leads to
      a decapping reaction, thereby exposing the mRNA to rapid 5' to 3' exonucleolytic
      degradation. A critical step in this pathway is decapping, since it effectively
      terminates the existence of the mRNA and is the site of numerous control inputs.
      In this review, we discuss the properties of the decapping enzyme and how its
      activity is regulated to give rise to differential mRNA turnover. A key point is
      that decapping appears to be controlled by access of the enzyme to the cap
      structure in a competition with the translation initiation complex. Strikingly,
      several proteins required for mRNA decapping show interactions with the
      translation machinery and suggest possible mechanisms for the triggering of mRNA
      decapping.

PMID- 10966470
TI  - Ribozyme structures and mechanisms.
AB  - The past few years have seen exciting advances in understanding the structure and
      function of catalytic RNA. Crystal structures of several ribozymes have provided
      detailed insight into the folds of RNA molecules. Models of other biologically
      important RNAs have been constructed based on structural, phylogenetic, and
      biochemical data. However, many questions regarding the catalytic mechanisms of
      ribozymes remain. This review compares the structures and possible catalytic
      mechanisms of four small self-cleaving RNAs: the hammerhead, hairpin, hepatitis
      delta virus, and in vitro-selected lead-dependent ribozymes. The organization of
      these small catalysts is contrasted to that of larger ribozymes, such as the
      group I intron.

PMID- 10966471
TI  - Aminoacyl-tRNA synthesis.
AB  - Aminoacyl-tRNAs are substrates for translation and are pivotal in determining how
      the genetic code is interpreted as amino acids. The function of aminoacyl-tRNA
      synthesis is to precisely match amino acids with tRNAs containing the
      corresponding anticodon. This is primarily achieved by the direct attachment of
      an amino acid to the corresponding tRNA by an aminoacyl-tRNA synthetase, although
      intrinsic proofreading and extrinsic editing are also essential in several cases.
      Recent studies of aminoacyl-tRNA synthesis, mainly prompted by the advent of
      whole genome sequencing and the availability of a vast body of structural data,
      have led to an expanded and more detailed picture of how aminoacyl-tRNAs are
      synthesized. This article reviews current knowledge of the biochemical,
      structural, and evolutionary facets of aminoacyl-tRNA synthesis.

PMID- 10966472
TI  - Structure and function of hexameric helicases.
AB  - Helicases are motor proteins that couple the hydrolysis of nucleoside
      triphosphate (NTPase) to nucleic acid unwinding. The hexameric helicases have a
      characteristic ring-shaped structure, and all, except the eukaryotic
      minichromosomal maintenance (MCM) helicase, are homohexamers. Most of the 12
      known hexameric helicases play a role in DNA replication, recombination, and
      transcription. A human genetic disorder, Bloom's syndrome, is associated with a
      defect in one member of the class of hexameric helicases. Significant progress
      has been made in understanding the biochemical properties, structures, and
      interactions of these helicases with DNA and nucleotides. Cooperativity in
      nucleotide binding was observed in many, and sequential NTPase catalysis has been
      observed in two proteins, gp4 of bacteriophage T7 and rho of Escherichia coli.
      The crystal structures of the oligomeric T7 gp4 helicase and the hexamer of RepA
      helicase show structural features that substantiate the observed cooperativity,
      and both are consistent with nucleotide binding at the subunit interface. Models
      are presented that show how sequential NTP hydrolysis can lead to unidirectional
      and processive translocation. Possible unwinding mechanisms based on the DNA
      exclusion model are proposed here, termed the wedge, torsional, and helix
      destabilizing models.

PMID- 10966473
TI  - Clathrin.
AB  - Clathrin was discovered nearly 25 years ago. Since then, a large number of other
      proteins that participate in the process by which clathrin-coated vesicles
      retrieve synaptic membranes or take up endocytic receptors have been identified.
      The functional relationships among these disparate components remain, in many
      cases, obscure. High-resolution structures of parts of clathrin, determined by X
      ray crystallography, and lower-resolution images of assembled coats, determined
      by electron cryomicroscopy, now provide the information necessary to integrate
      various lines of evidence and to design experiments that test specific
      mechanistic notions. This review summarizes and illustrates the recent structural
      results and outlines what is known about coated-vesicle assembly in the context
      of this information.

PMID- 10966474
TI  - Mediator of transcriptional regulation.
AB  - Three lines of evidence have converged on a multiprotein Mediator complex as a
      conserved interface between gene-specific regulatory proteins and the general
      transcription apparatus of eukaryotes. Mediator was discovered as an activity
      required for transcriptional activation in a reconstituted system from yeast.
      Upon resolution to homogeneity, the activity proved to reside in a 20-protein
      complex, which could exist in a free state or in a complex with RNA polymerase
      II, termed holoenzyme. A second line of evidence came from screens in yeast for
      mutations affecting transcription. Two-thirds of Mediator subunits are encoded by
      genes revealed by these screens. Five of the genetically defined subunits, termed
      Srbs, were characterized as interacting with the C-terminal domain of RNA
      polymerase II in vivo, and were shown to bind polymerase in vitro. A third line
      of evidence has come recently from studies in mammalian transcription systems.
      Mammalian counterparts of yeast Mediator were shown to interact with
      transcriptional activator proteins and to play an essential role in
      transcriptional regulation. Mediator evidently integrates and transduces positive
      and negative regulatory information from enhancers and operators to promoters. It
      functions directly through RNA polymerase II, modulating its activity in promoter
      dependent transcription. Details of the Mediator mechanism remain obscure.
      Additional outstanding questions include the patterns of promoter-specificity of
      the various Mediator subunits, the possible cell-type-specificity of Mediator
      subunit composition, and the full structures of both free Mediator and RNA
      polymerase II holoenzyme.

PMID- 10966475
TI  - Critical analysis of antibody catalysis.
AB  - Antibody molecules elicited with rationally designed transition-state analogs
      catalyze numerous reactions, including many that cannot be achieved by standard
      chemical methods. Although relatively primitive when compared with natural
      enzymes, these catalysts are valuable tools for probing the origins and evolution
      of biological catalysis. Mechanistic and structural analyses of representative
      antibody catalysts, generated with a variety of strategies for several different
      reaction types, suggest that their modest efficiency is a consequence of
      imperfect hapten design and indirect selection. Development of improved
      transition-state analogs, refinements in immunization and screening protocols,
      and elaboration of general strategies for augmenting the efficiency of first
      generation catalytic antibodies are identified as evident, but difficult,
      challenges for this field. Rising to these challenges and more successfully
      integrating programmable design with the selective forces of biology will enhance
      our understanding of enzymatic catalysis. Further, it should yield useful protein
      catalysts for an enhanced range of practical applications in chemistry and
      biology.

PMID- 10966476
TI  - GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein
      signaling (RGS) and RGS-like proteins.
AB  - GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by
      increasing the rates at which their subunits hydrolyze bound GTP and thus return
      to the inactive state. G protein GAPs act allosterically on G subunits, in
      contrast to GAPs for the Ras-like monomeric GTP-binding proteins. Although they
      do not contribute directly to the chemistry of GTP hydrolysis, G protein GAPs can
      accelerate hydrolysis >2000-fold. G protein GAPs include both effector proteins
      (phospholipase C-?, p115RhoGEF) and a growing family of regulators of G protein
      signaling (RGS proteins) that are found throughout the animal and fungal
      kingdoms. GAP activity can sharpen the termination of a signal upon removal of
      stimulus, attenuate a signal either as a feedback inhibitor or in response to a
      second input, promote regulatory association of other proteins, or redirect
      signaling within a G protein signaling network. GAPs are regulated by various
      controls of their cellular concentrations, by complex interactions with G? or
      with G?5 through an endogenous G-like domain, and by interaction with multiple
      other proteins.

PMID- 10966477
TI  - Regulation of chromosome replication.
AB  - The initiation of DNA replication in eukaryotic cells is tightly controlled to
      ensure that the genome is faithfully duplicated once each cell cycle. Genetic and
      biochemical studies in several model systems indicate that initiation is mediated
      by a common set of proteins, present in all eukaryotic species, and that the
      activities of these proteins are regulated during the cell cycle by specific
      protein kinases. Here we review the properties of the initiation proteins, their
      interactions with each other, and with origins of DNA replication. We also
      describe recent advances in understanding how the regulatory protein kinases
      control the progress of the initiation reaction. Finally, we describe the
      checkpoint mechanisms that function to preserve the integrity of the genome when
      the normal course of genome duplication is perturbed by factors that damage the
      DNA or inhibit DNA synthesis.

PMID- 10966478
TI  - Helical membrane protein folding, stability, and evolution.
AB  - Helical membrane protein folding and oligomerization can be usefully
      conceptualized as involving two energetically distinct stages-the formation and
      subsequent side-to-side association of independently stable transbilayer helices.
      The interactions of helices with the bilayer, with prosthetic groups, and with
      each other are examined in the context of recent evidence. We conclude that the
      two-stage concept remains useful as an approach to simplifying discussions of
      stability, as a framework for folding concepts, and as a basis for understanding
      membrane protein evolution.

PMID- 10966479
TI  - Synthesis of native proteins by chemical ligation.
AB  - In just a few short years, the chemical ligation of unprotected peptide segments
      in aqueous solution has established itself as the most practical method for the
      total synthesis of native proteins. A wide range of proteins has been prepared.
      These synthetic molecules have led to the elucidation of gene function, to the
      discovery of novel biology, and to the determination of new three-dimensional
      protein structures by both NMR and X-ray crystallography. The facile access to
      novel analogs provided by chemical protein synthesis has led to original insights
      into the molecular basis of protein function in a number of systems. Chemical
      protein synthesis has also enabled the systematic development of proteins with
      enhanced potency and specificity as candidate therapeutic agents.

PMID- 10966480
TI  - Swinging arms and swinging domains in multifunctional enzymes: catalytic machines
      for multistep reactions.
AB  - Multistep chemical reactions are increasingly seen as important in a growing
      number of complex biotransformations. Covalently attached prosthetic groups or
      swinging arms, and their associated protein domains, are essential to the
      mechanisms of active-site coupling and substrate channeling in a number of the
      multifunctional enzyme systems responsible. The protein domains, for which the
      posttranslational machinery in the cell is highly specific, are crucially
      important, contributing to the processes of molecular recognition that define and
      protect the substrates and the catalytic intermediates. The domains have novel
      folds and move by virtue of conformationally flexible linker regions that tether
      them to other components of their respective multienzyme complexes. Structural
      and mechanistic imperatives are becoming apparent as the assembly pathways and
      the coupling of multistep reactions catalyzed by these dauntingly complex
      molecular machines are unraveled.

PMID- 10966481
TI  - Structure and function of cytochrome bc complexes.
AB  - The cytochrome bc complexes represent a phylogenetically diverse group of
      complexes of electron-transferring membrane proteins, most familiarly represented
      by the mitochondrial and bacterial bc1 complexes and the chloroplast and
      cyanobacterial b6f complex. All these complexes couple electron transfer to
      proton translocation across a closed lipid bilayer membrane, conserving the free
      energy released by the oxidation-reduction process in the form of an
      electrochemical proton gradient across the membrane. Recent exciting developments
      include the application of site-directed mutagenesis to define the role of
      conserved residues, and the emergence over the past five years of X-ray
      structures for several mitochondrial complexes, and for two important domains of
      the b6f complex.

PMID- 10966483
TI  - An altered repolarizing potassium current in rat cardiac myocytes after subtotal
      nephrectomy.
AB  - Renal failure in humans is associated with electrocardiographic changes including
      altered QT interval dispersion, which suggests that cardiac myocyte
      repolarization is abnormal and which appears to correlate with cardiac prognosis.
      In this study, cardiac myocyte repolarizing currents have been studied in
      isolated cells from rats 8 wk after subtotal nephrectomy (SNx), using sham
      operated animals as controls. In addition, monophasic cardiac action potentials
      were recorded from the epicardial surface of the left ventricle (LV) apex, LV
      base, and the right ventricle of isolated perfused hearts paced at 320/min. SNx
      was associated with cardiac hypertrophy and histologic evidence of myocardial
      fibrosis, but SNx rats were not hypertensive. Repolarizing K(+) currents were
      measured using whole-cell patch-clamp, and 4-aminopyridine (4-AP)-sensitive
      transient outward (I(to)) and 4-AP-insensitive sustained outward (I(so))
      components were quantified. After SNx, I(to) was increased by two to threefold at
      voltages from -30 to +60 mV and showed increased heterogeneity. For example, at 0
      mV voltage clamp pulse, the median I(to) was increased from 3.23 pA/pF in control
      myocytes (interquartile range 3.20 pA/pF, n = 24) to 5.86 pA/pF in SNx myocytes
      (interquartile range 7.32 pA/pF, n = 21, P: < 0.005). The kinetics of
      inactivation of I(to) were altered after SNx with slowing both of the onset and
      the recovery from inactivation. The mean time constant of inactivation at +30 mV
      after SNx was 14.2 +/- 1.6 ms (n = 20) compared with control values of 9.8 +/-
      0.6 ms (n = 23, P: < 0.05). Neither I(so) nor inward rectifier K(+) currents were
      altered after SNx. The action potential duration (APD(50)) at the left
      ventricular base was approximately 20% shorter (P: < 0.02) in hearts from SNx
      rats compared with controls. 4-AP (2 mM) prolonged the APD(50) in all regions in
      hearts from both SNx and control rats and abolished the APD(50) shortening in
      SNx. These results indicate that abnormalities of the cardiac transient outward
      K(+) current contribute to alterations in the cardiac action potential in renal
      failure and warrant further investigation because they may contribute to altered
      repolarization and arrythmogenesis.

PMID- 10966482
TI  - Effect of acidosis on the properties of the glutaminase mRNA pH-response element
      binding protein.
AB  - The pH-responsive stabilization of the rat renal glutaminase (GA) mRNA during
      metabolic acidosis is mediated by a pH-response element (pH-RE). The primary pH
      RE within the GA mRNA consists of a direct repeat of an 8-base adenosine and
      uridine-rich sequence, which binds a specific cytosolic protein, the pH-response
      element binding protein (REBP). The functional analysis of this system was
      performed in LLC-PK(1)-F(+) cells, a pH-responsive line of porcine proximal
      tubule-like cells. Cytosolic extracts of LLC-PK(1)-F(+) cells also contain a
      protein that binds with high affinity to the rat GA mRNA pH-RE. The apparent
      binding of this protein is increased threefold in cytosolic extracts prepared
      from LLC-PK(1)-F(+) cells that were grown in acidic medium (pH = 6.9, HCO(3)- =
      10 mM). Extracts prepared from the renal cortex of rats that were made acutely
      acidotic also exhibit a similar increase in binding to the RNA probe that
      contains the direct repeat of the pH-RE. The temporal increase in binding
      correlates with the temporal increase in GA mRNA. Scatchard analysis indicates
      that the increased binding is due to an increase in both the affinity and the
      maximal binding of the pH-REBP. Thus, increased binding of the pH-REBP to the GA
      mRNA may initiate its stabilization and increased expression during acidosis.

PMID- 10966484
TI  - Role of Ras isoforms in the stimulated proliferation of human renal fibroblasts
      in primary culture.
AB  - The proliferation of renal fibroblasts is implicated in the pathophysiologic
      processes of renal fibrosis. Many of the growth factors involved in proliferation
      are known to activate intracellular signaling pathways that converge on Ras
      monomeric GTPases. Although three ras family genes exist, their functional
      specificity is not yet known. Using antisense oligonucleotides, a role for
      Kirsten (Ki)-Ras in the stimulated proliferation of a primate renal fibroblast
      cell line was previously demonstrated. This study examines Ras in primary
      cultures of adult human renal fibroblasts. Using reverse transcription-PCR, mRNA
      for Harvey (Ha)-ras, Ki(4B)-ras, and neural (N)-ras, but not Ki(4A)-ras, were
      detected. Antisense oligonucleotides targeting Ha-, Ki-, and N-ras mRNA, which
      were used for liposomal transfection at 100 to 200 nM, were demonstrated to be
      active and isoform-specific in quantitative reverse transcription-PCR assays.
      Cellular Ras protein levels, as estimated using isoform-specific monoclonal
      antibodies, indicated that Ki-Ras was the predominantly expressed isoform (>95%
      of total Ras protein) under both serum-containing and serum-free conditions, with
      N- and Ha-Ras being detected in small amounts. Consistent with this finding, the
      antisense oligonucleotide directed against Ki-Ras reduced total cellular Ras
      levels by >70%, whereas Ha-Ras, N-Ras, and control oligonucleotides had no
      significant effect. Proliferation of oligonucleotide-transfected cells was
      measured using epidermal growth factor (EGF) and serum stimulation. The Ki-Ras
      oligonucleotide at 100 nM reduced serum-stimulated proliferation by >50% and EGF
      stimulated proliferation by 25%, compared with data obtained with the control
      oligonucleotide (P: < 0. 01). The N-Ras oligonucleotide was not active, compared
      with the control oligonucleotide. The Ha-Ras oligonucleotide was not
      significantly active at 100 nM but reduced serum-stimulated proliferation by 13%
      and EGF-stimulated growth by 40% at 200 nM (P: < 0.01). These results demonstrate
      that Ki-Ras(4B) is the predominantly expressed Ras isoform in human renal
      fibroblasts in primary culture and is important for both serum- and EGF
      stimulated proliferation. Ha-Ras appears to be expressed at low levels but may
      also play a distinct role in stimulated proliferation.

PMID- 10966485
TI  - The decorin high glucose response element and mechanism of its activation in
      human mesangial cells.
AB  - The decorin gene encodes a proteoglycan with putative structural and regulatory
      functions whose expression is markedly increased in human mesangial cells (HMC)
      exposed to high concentrations of glucose (15 to 30 mM). The gene has two
      promoters (P1 and P2) upstream of two alternative first exons. Transcripts driven
      by both promoters are present in HMC maintained in 4 mM D-glucose medium. After
      exposure to 30 mM D-glucose for 7 to 21 d, transcripts driven by P1 are markedly
      increased, whereas those driven by P2 decrease. Culture in 4 mM D-glucose medium
      containing transforming growth factor-beta1 (TGF-beta1) (1.25 ng/ml) has the same
      effect. However, addition of an excess of TGF-beta neutralizing antibody to the
      30 mM D-glucose cultures only partly suppressed increased decorin transcription
      from P1. In transformed HMC transfected with a reporter (p-SAEP) driven by P1 or
      P2, P1 activity increased twofold on treatment with either 30 mM D-glucose or TGF
      beta1 in 4 mM medium. P2 had little activity under any conditions. 5' deletion of
      P1 showed that basal transcriptional activity lies within the proximal 378 bp,
      while the major high glucose and TGF-beta response element is located in the -683
      to -583-bp region. A putative cAMP response-like sequence (TGACGTTT) lies within
      this region. Electrophoretic mobility shift assays revealed the same pattern of
      multiple complexes between oligonucleotides containing this sequence and nuclear
      proteins extracted from HMC maintained in either 4 or 30 mM D-glucose conditions,
      but the latter were more prominent. cAMP response element binding protein (CREB)
      was identified as one transcription factor forming these complexes but other
      factors remain unidentified. Increased levels of phospho-(Ser 133) CREB were
      found in HMC exposed to 30 mM D-glucose. High glucose also activated and led to
      nuclear translocation of p42/44 mitogen-activated protein kinase and p38 mitogen
      activated protein kinase, both of which can activate CREB by phosphorylation of
      serine 133.

PMID- 10966486
TI  - Activation of DNA synthesis and AP-1 by profilin, an actin-binding protein, via
      binding to a cell surface receptor in cultured rat mesangial cells.
AB  - Profilin is known to bind to actin monomers (to regulate actin polymerization)
      and to phosphatidylinositol-4,5-bisphosphate (to inhibit hydrolysis by
      unphosphorylated phospholipase C-gammal). It was recently reported that profilin
      is overexpressed in glomerular mesangial cells (MC) of rats with anti-Thy-1.1
      induced glomerulonephritis and is accumulated in the extracellular space around
      MC. In this study, the biologic activities of extracellular profilin were
      examined. Scatchard analysis indicated the existence of a single class of cell
      surface binding sites, with similar equilibrium dissociation constants for
      purified splenic profilin and recombinant profilin, in cultured rat MC. Profilin
      increased [(3)H]thymidine incorporation in a dose-dependent manner and produced
      additive effects on platelet-derived growth factor-induced [(3)H]thymidine
      incorporation. Profilin increased AP-1 DNA-binding activity in a concentration
      dependent (ED(50) = 30 nM) and time-dependent manner after transient c-jun gene
      expression, as measured using gel-shift assays and competitive reverse
      transcription-PCR. Pretreatment of profilin with an anti-profilin inhibitory
      antibody suppressed profilin-induced AP-1 activation and [(3)H]thymidine
      incorporation. Furthermore, profilin induced rapid transient activation of
      protein kinase C, and staurosporine and H-7 reduced the profilin-induced
      activation of AP-1, suggesting protein kinase C-dependent activation of AP-1.
      These findings indicate that profilin in the extracellular space can bind to cell
      surface receptors of MC and act as an inducer of signal transduction. These
      results suggest that extracellular profilin may be involved in the progression of
      glomerular diseases, by affecting cell growth.

PMID- 10966487
TI  - Modification of the epidermal growth factor response by ammonia in renal cell
      hypertrophy.
AB  - Epidermal growth factor (EGF) causes proliferation in renal tubular cells but,
      when it is combined with transforming growth factor-beta1, it causes hypertrophy
      by a mechanism that requires the activity of the retinoblastoma family of
      proteins. In contrast, ammonia causes hypertrophy by decreasing lysosomal
      proteolysis; in some cell types, it also decreases cellular proliferation. These
      studies were designed to determine whether ammonia, like transforming growth
      factor-beta1, could convert EGF-induced hyperplasia to hypertrophy. Cultured NRK
      52E cells were incubated with EGF and/or ammonia and the protein/DNA ratio was
      measured, as a marker of hypertrophy. Addition of ammonia to EGF-treated NRK-52E
      cells converted EGF-induced hyperplasia to hypertrophy, because of a decrease in
      DNA synthesis. The mechanism involved no change in EGF-induced protein synthesis.
      Inhibition of lysosomal function with a proton pump inhibitor or lysosomal
      protease inhibitors also converted the response of EGF-treated cells to
      hypertrophy. Expression of the human papilloma virus 16 E7 protein (which
      inactivates all members of the retinoblastoma family) prevented ammonia from
      converting EGF-induced hyperplasia to hypertrophy. It is concluded that ammonia
      converts EGF-induced hyperplasia to hypertrophy by a mechanism that involves
      suppression of lysosomal function and this response can be blocked by inhibiting
      the activity of the retinoblastoma family of proteins.

PMID- 10966488
TI  - Upregulation of CD14 and CD18 on monocytes In vitro by antineutrophil cytoplasmic
      autoantibodies.
AB  - The expression of CD14, CD18, and major histocompatibility complex II on unprimed
      monocytes from healthy donors after incubation with IgG from patients with
      antineutrophil cytoplasmic autoantibody (ANCA)-positive active Wegener's
      granulomatosis (n = 6) and microscopic polyangiitis (n = 6) in comparison with
      IgG from healthy controls (n = 6) was studied. Monocytes were incubated with IgG
      (100 microg/ml) at 37 degrees C, and expression of antigens was measured by
      fluorescence-activated cell sorter after 18 h. Cytoplasmic ANCA (C-ANCA) IgG and
      perinuclear ANCA (P-ANCA) IgG in comparison with control IgG increased the
      expression of CD14 (49.2% [SD: 37, P: < 0. 001], and 55.8% [SD: 41, P: < 0.05])
      and CD18 (11.4% [SD: 18, P: < 0. 01] and 8% [SD: 26, P: < 0.05]) but did not
      change the major histocompatibility complex II expression. Upregulation of CD14
      started after 6 h and reached a peak after 10 to 14 h of incubation and was not
      inhibited by polymyxin B. F(ab)(2) fragments of C- and P-ANCA IgG also increased
      expression of CD14 and CD18 as compared with control IgG F(ab)(2), but for CD14
      less than with complete IgG. ANCA IgG depleted of antiproteinase 3 and
      antimyeloperoxidase antibodies by immunoadsorption failed to upregulate CD14.
      Monoclonal murine antibodies against proteinase 3 and myeloperoxidase yielded a
      strong upregulation of CD14 when compared with an isotype control or human
      control IgG. The data show that CD14 and CD18 are upregulated on monocytes by C-
      and P-ANCA IgG in vitro, as well as by monoclonal antibodies against proteinase 3
      and myeloperoxidase and that this effect is not dependent on Fc gamma receptor
      crosslinking. Upregulation of CD14 and CD18 on monocytes by ANCA suggests a
      pathogenetic role of ANCA monocyte interactions in systemic vasculitis.

PMID- 10966489
TI  - Lack of in vivo function of osteopontin in experimental anti-GBM nephritis.
AB  - Osteopontin (Opn) is a potent chemoattractant for mononuclear cells that is
      upregulated in various inflammatory states of the kidney. Opn is believed to
      contribute to mononuclear cell infiltration and renal injury. The importance of
      Opn was examined in vivo in rapidly progressive glomerulonephritis in Opn
      knockout mice. Glomerulonephritis was induced by intravenous injection of rabbit
      anti-mouse glomerular basement membrane antiserum in mice that had been
      presensitized to rabbit IgG. Immunologic responsiveness to rabbit IgG (assessed
      by cutaneous delayed-type hypersensitivity and antibody titers) showed no
      significant difference between wild-type and Opn -/- mice. Proteinuria was also
      similar in both groups. Glomerular crescent formation was not different in Opn
      +/+ and -/- groups (26 +/- 6% versus 29 +/- 7%). Tubulointerstitial infiltration
      was assessed qualitatively and showed no significant difference between the two
      genotypes. Formation of thrombi in the glomerular capillaries on a scale from 0
      to 3 also showed no significant difference (1.3 +/- 0.3 for Opn +/+ and 1.4 +/-
      0.3 for Opn -/- mice). Northern blot analysis of total kidney RNA showed a 5.1
      fold increase of Opn expression in Opn +/+ mice compared with untreated controls
      and the absence of expression in Opn -/- mice, as expected. Regulated upon
      activation, normal T cell expressed and secreted (RANTES) and monocyte
      chemoattractant protein-1 mRNA levels were also markedly upregulated with no
      significant difference between the two strains, excluding compensatory
      overexpression of these two chemokines in Opn -/- mice. It is concluded that the
      known upregulation of Opn in murine anti-glomerular basement membrane nephritis
      does not significantly contribute to the glomerular and tubulointerstitial
      mononuclear cell infiltration in this model.

PMID- 10966491
TI  - Type 2 diabetic patients with nephropathy show structural-functional
      relationships that are similar to type 1 disease.
AB  - Glomerular structural-functional relationships were investigated in 21 type 2
      diabetic patients with proteinuria. Structural parameters were quantified using
      both light and electron microscopy and standard stereologic techniques. Data were
      also available on 14 nondiabetic subjects. Mesangial and matrix volume fractions
      and glomerular basement membrane (GBM) width were increased in type 2 patients
      when compared with nondiabetic subjects (mean +/- SD: 0.45 +/- 0.13 versus 0.18
      +/- 0.03, P: < 0.001; 0.28 +/- 0.09 versus 0.10 +/- 0.02, P: < 0.001; and 665 +/-
      138 versus 361 +/- 51 nm, P: < 0. 001, respectively). An increase in mesangial
      volume fraction was associated with high levels of proteinuria and low creatinine
      clearance (r = 0.64, P: = 0.002; r = -0.58, P: = 0.006, respectively). GBM width
      and mesangial foot process width (FPW(mes)) also correlated with proteinuria (r =
      0.58, P: = 0.006; r = 0.60, P: = 0.004, respectively). Volume fraction of
      interstitium correlated with creatinine clearance (r = -0.58, P: = 0.006).
      Patients had previously been defined by light microscopy as having either diffuse
      or nodular glomerulosclerosis; those with nodules had larger mesangial and matrix
      volume fractions and more proteinuria than those classified as diffuse (mean +/-
      SD: 0.51 +/- 0.12 versus 0.36 +/- 0.08, P: = 0.007; 0.32 +/- 0.08 versus 0.21 +/-
      0.05, P: = 0. 003; median, range: 4.3, 1.1 to 9.6 versus 1.1, 0.9 to 12.7 g/24 h,
      P: = 0.027). Creatinine clearance did not differ significantly between the
      groups. Type 2 diabetic patients with proteinuria have established
      glomerulopathy, which is more advanced in those with nodular glomerulosclerosis.
      Creatinine clearance correlated with both mesangial and interstitial expansion,
      whereas proteinuria correlated only with glomerular pathology. These results
      suggest that type 2 patients with advanced nephropathy have structural-functional
      relationships similar to type 1, consistent with a common pathogenesis, and
      strongly support an important role of the tubulointerstitium in the role of renal
      impairment.

PMID- 10966490
TI  - Expression of advanced glycation end products and their cellular receptor RAGE in
      diabetic nephropathy and nondiabetic renal disease.
AB  - Advanced glycation end products (AGE) contribute to diabetic tissue injury by two
      major mechanisms, i.e., the alteration of extracellular matrix architecture
      through nonenzymatic glycation, with formation of protein crosslinks, and the
      modulation of cellular functions through interactions with specific cell surface
      receptors, the best characterized of which is the receptor for AGE (RAGE). Recent
      evidence suggests that the AGE-RAGE interaction may also be promoted by
      inflammatory processes and oxidative cellular injury. To characterize the
      distributions of AGE and RAGE in diabetic kidneys and to determine their
      specificity for diabetic nephropathy, an immunohistochemical analysis of renal
      biopsies from patients with diabetic nephropathy (n = 26), hypertensive
      nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11),
      focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and
      from normal control subjects (n = 2) was performed, using affinity-purified
      antibodies raised to RAGE and two subclasses of AGE, i.e., N(epsilon)
      (carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in
      diffuse and nodular diabetic nephropathy. CML was the major AGE detected in
      diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular
      basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT
      was preferentially located in interstitial collagen (90%) and was less
      consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and
      tubular basement membranes (31%). RAGE was expressed on normal podocytes and was
      upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to
      glomeruli was confirmed by reverse transcription-PCR analysis of microdissected
      renal tissue compartments. The extent of mesangial and GBM immunoreactivity for
      CML, but not PENT, was correlated with the severity of diabetic
      glomerulosclerosis, as assessed pathologically. CML and PENT were also identified
      in areas of glomerulosclerosis and arteriosclerosis in idiopathic and secondary
      focal segmental glomerulosclerosis, hypertensive nephrosclerosis, and lupus
      nephritis. In active lupus nephritis, CML and PENT were detected in the
      proliferative glomerular tufts and crescents. In conclusion, CML is a major AGE
      in renal basement membranes in diabetic nephropathy, and its accumulation
      involves upregulation of RAGE on podocytes. AGE are also accumulated in acute
      inflammatory glomerulonephritis secondary to systemic lupus erythematosus,
      possibly via enzymatic oxidation of glomerular matrix proteins.

PMID- 10966492
TI  - A locus for adolescent and adult onset familial focal segmental
      glomerulosclerosis on chromosome 1q25-31.
AB  - Focal segmental glomerulosclerosis is a nonspecific renal lesion observed both as
      a primary (idiopathic) entity and in a secondary form, typically in association
      with reduced functional renal mass. Familial forms have been observed and two
      loci for autosomal dominant FSGS have been mapped. This study shows that an
      adolescent/adult form of recessive FSGS maps to a locus on chromosome 1q25-31,
      which overlaps with a region previously identified as harboring a locus for an
      early childhood onset recessive form of nephrotic syndrome (SRN1). Evaluation of
      a large family demonstrated linkage with a maximum two-point lod score of 3.98 at
      D1S254 and D1S222. Lod score calculations support the conclusion of linkage in
      four of five additional families. Haplotype analysis suggests that this FSGS gene
      is located in a 19-cM region flanked by D1S416 and D1S413, of which 6 cM overlaps
      with SRN1, suggesting that these distinct clinical subsets of kidney disease may
      be allelic. These regions may also overlap with the syntenic region of the
      glomerulosclerosis susceptibility locus in the BUF/Mna rat. Because the
      presentation of FSGS may be subtle, inherited FSGS may be much more common than
      generally realized and grossly underestimated because of the absence of clear
      familial patterns. This result increases the suspicion that polymorphisms at this
      locus may contribute to sporadic FSGS.

PMID- 10966493
TI  - Induction of CD14 in tubular epithelial cells during kidney disease.
AB  - Analysis of gene expression in a mouse model of unilateral ureteral obstruction
      (UUO) revealed significant induction of CD14 mRNA in kidneys with obstructed
      ureters. Immunocytochemical analysis indicated that CD14 was upregulated in
      tubular epithelial cells and this upregulation was not attributable to
      infiltration of the kidneys by mononuclear cells. This induction of CD14 mRNA was
      found to occur in BALB/C, C57BL/6, C3H/HeN, and C3H/HeJ mice during UUO.
      Ischemia/reperfusion of kidneys also induced CD14 mRNA. Mice lacking either of
      the tumor necrosis factor-alpha receptor (TNFR) genes were also studied; the
      induction of CD14 was blunted in TNFR 1-knockout mice but not in TNFR2-knockout
      mice. Apoptosis of tubular cells in lipopolysaccharide-resistant CH3/HeJ mice was
      significantly (P: < 0. 05) less than that in lipopolysaccharide-responsive
      CH3/HeN mice during UUO. These results suggest that CD14 is acutely induced in
      tubular epithelial cells in two mouse models of renal injury. This induction is
      regulated by tumor necrosis factor-alpha, through TNFR1. CD14 may participate in
      the apoptosis of tubular epithelial cells on a more chronic basis by activating a
      pathway that is absent or deficient in C3H/HeJ mice.

PMID- 10966494
TI  - Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide
      with renal ablation.
AB  - Brain natriuretic peptide (BNP) is a cardiac hormone produced by the ventricle,
      and its secretion is markedly increased in heart failure, hypertension, and renal
      failure. Transgenic mice that overexpress BNP in the liver (BNP-Tg) were recently
      generated, resulting in low BP. To elucidate the role of BNP in renal
      pathophysiology, the effect of chronic excess of BNP in transgenic mice on
      glomerular injury after subtotal nephrectomy induced by resection of the renal
      poles was examined. After nephrectomy, glomerular cross-sectional areas in
      control nontransgenic mice markedly increased as compared with those in sham
      operated mice (+81 +/- 7%), whereas there was only a modest increase in BNP-Tg
      (+10 +/- 6%). Expansion of the mesangial area and increase in the intraglomerular
      cell number were also inhibited in BNP-Tg. Glomerular expressions of transforming
      growth factor-beta and fibronectin were increased with hypertrophy and were
      significantly suppressed in BNP-Tg. Furthermore, increases in the urinary albumin
      excretion and BP were significantly ameliorated in BNP-Tg. Chronic hydralazine
      treatment in nephrectomized nontransgenic mice failed to inhibit glomerular
      hypertrophy. These findings indicate that the chronic excess of BNP in mice
      ameliorates glomerular hypertrophy and mesangial expansion after renal ablation.
      The results also suggest that the observed effects of natriuretic peptides under
      reduced renal mass are not due merely to systemic BP reduction and may be
      therapeutically applicable in various renal diseases.

PMID- 10966495
TI  - Endothelin A receptor blockade prevents capillary/myocyte mismatch in the heart
      of uremic animals.
AB  - In the heart of uremic animals and patients, the number of capillaries per volume
      of myocardium is reduced. Immunohistochemical studies demonstrated increased
      cardiac endothelin-1 (ET-1) expression in the left ventricle of uremic animals.
      Therefore, whether treatment with a selective ET(A)-receptor antagonist prevented
      such capillary-myocyte mismatch was investigated. Twenty-four h after subtotal
      nephrectomy, rats were left untreated or started on treatment with the ET(A)
      receptor antagonist LU 135252 (20 mg/kg per d) and with the angiotensin
      converting enzyme (ACE) inhibitor trandolapril (0.3 mg/kg per d), respectively.
      BP was monitored by telemetry. Myocardial capillary length density was analyzed
      by stereologic techniques that avoid anisotropy artifacts. In addition, cardiac
      ET-1 protein and mRNA were measured using immunohistochemistry, in situ
      hybridization, and quantitative reverse transcription-PCR. Changes in cardiac
      ET(A)-and ET(B)-PCR. receptor mRNA were measured using reverse transcription-PCR.
      Fifteen wk after subtotal nephrectomy, significantly reduced left ventricular
      capillary length density (3307 +/- 535 mm/mm(3)) was found compared with sham
      operated controls (3995 +/- 471 mm/mm(3)); this was also seen in animals that
      were treated with trandolapril (3503 +/- 533 mm/mm(3)) but not in animals that
      were treated with LU 135252 (3800 +/- 303 mm/mm(3)). The results support a role
      of ET-1 in the genesis of left ventricular capillary/myocyte mismatch in uremia.

PMID- 10966496
TI  - Effect of high extracellular phosphate concentration on arachidonic acid
      production by parathyroid tissue in vitro.
AB  - Recent in vivo and in vitro studies show that high phosphate directly stimulates
      parathyroid hormone (PTH) secretion. However, little is known about the
      intracellular signaling system involved in the regulation of PTH secretion by
      extracellular phosphate. High extracellular calcium is coupled to the activation
      of phospholipase A(2) (PLA(2)) and the formation of arachidonic acid (AA), a
      potent inhibitor of PTH release. The present study was designed to evaluate
      whether a high phosphate concentration has an effect on the PLA(2)-AA pathway in
      parathyroid cells. In vitro experiments were performed in parathyroid tissue
      obtained from normal rats and dogs. AA production was measured in parathyroid
      tissue in response to 1- and 4-mM phosphate concentration and after addition of
      PLA(2) to the medium. To determine whether the effect of phosphate on AA
      production in parathyroid cells was tissue specific, separate experiments were
      performed to test the effect of phosphate in rat adrenal glomerulosa cells, which
      are known to increase AA production in response to angiotensin II. The effect of
      sulfate, an ion with chemical characteristics similar to phosphate, on PTH
      secretion was also evaluated. In parathyroid tissue, a high phosphate
      concentration decreased the high calcium-induced AA production. This effect of
      phosphate was associated with an increase in PTH secretion. The addition of AA
      reversed the stimulatory effect of phosphate on PTH secretion. In another type of
      AA-responsive tissue, the adrenal glomerulosa, a high phosphate concentration did
      not affect the production of AA when stimulated by angiotensin II. In a normal
      phosphate concentration, the addition of PLA(2) stimulated AA production and
      decreased the PTH secretion. However, in a 4-mM phosphate concentration, the
      addition of PLA(2) did not reduce PTH secretion and did not stimulate AA
      production. Finally, sulfate did not affect PTH secretion. In conclusion, a high
      phosphate concentration affects the production of AA by parathyroid tissue. This
      effect of phosphate may be the mechanism by which a high phosphate concentration
      stimulates PTH secretion.

PMID- 10966497
TI  - Mechanism of the inhibitory effect of OPB-9195 [(+/-)-2-isopropylidenehydrazono-4
      oxo-thiazolidin-5-yla cetanilide] on advanced glycation end product and advanced
      lipoxidation end product formation.
AB  - The accumulation in uremic plasma of reactive carbonyl compounds (RCO) derived
      from both carbohydrates and lipids ("carbonyl stress") contributes to uremic
      toxicity by accelerating the advanced glycation and lipoxidation of proteins. It
      was previously demonstrated that OPB-9195 [(+/-)-2-isopropylidenehydrazono-4-oxo-
      thiazolidin-5-ylacetanilide] inhibited the in vitro formation of advanced
      glycation end products (AGE) in uremic plasma. This study was designed to
      elucidate the mechanism of action of OPB-9195 by further delineating the AGE and
      advanced lipoxidation end product (ALE) precursors targeted by this drug. The
      inhibitory effects of OPB-9195 on the formation of two AGE (N:epsilon
      carboxymethyllysine and pentosidine) on bovine serum albumin incubated with
      various AGE precursors were examined. Inhibition of N:epsilon-carboxymethyllysine
      and pentosidine formation with OPB-9195 was more efficient than with
      aminoguanidine. OPB-9195 also proved effective in blocking the carbonyl amine
      chemical processes involved in the formation of two ALE (malondialdehyde-lysine
      and 4-hydroxynonenal-protein adduct). The efficiency of OPB-9195 was similar to
      that of aminoguanidine. When glucose-based peritoneal dialysis fluid was
      incubated in the presence of OPB-9195, a similar inhibition of AGE formation was
      observed. The direct effect of OPB-9195 on major glucose-derived RCO in
      peritoneal dialysis fluids was then evaluated. The effects of OPB-9195 could be
      accounted for by its ability to trap RCO. The concentrations of three major
      glucose-derived RCO (glyoxal, methylglyoxal, and 3-deoxy-glucosone) were
      significantly lower in the presence of OPB-9195 than in its absence.
      Aminoguanidine had a similar effect. In conclusion, OPB-9195 inhibits both AGE
      and ALE formation, probably through its ability to trap RCO. OPB-9195 might prove
      to be a useful tool to inhibit some of the effects of RCO-related uremic
      toxicity.

PMID- 10966498
TI  - Evidence in vivo showing increase of baseline nitric oxide generation and
      impairment of endothelium-dependent vasodilation in normotensive patients on
      chronic hemodialysis.
AB  - Cardiovascular mortality is excessive in hemodialyzed patients. Observations in
      atherosclerosis suggest that endothelial dysfunction and impaired nitric oxide
      (NO) may be involved. However, the relation of endothelial NO to its vascular
      effects has not been studied conclusively in uremia. Therefore, to study these
      questions an invasive technique was used in normotensive patients who were on
      hemodialysis (HD; n = 11) and in matched control subjects (n = 11). Pharmacologic
      agents were infused into the brachial artery to test the chain of events from NO
      generation to smooth muscle cell relaxation, measuring forearm blood flow by
      venous occlusion plethysmography. Glyceroltrinitrate (GTN 1:2.2 nmol/min; GTN
      2:4.4; GTN 3:8.8), infused to establish the reaction of the vessel wall to
      defined doses of NO, caused a reduced response in HD patients (control subjects:
      183 +/- 20 [SEM], 246 +/- 26, and 338 +/- 29%; HD patients: 161 +/- 7, 206 +/-
      12, and 262 +/- 24%; baseline = 100% for each group, P: = 0.032 by ANOVA). All
      subsequent data were corrected for this decreased response to defined doses of NO
      in HD patients. L-arginine (10 mg/min), given to exclude substrate deficiency of
      NO synthase (NOS), caused no significant changes (control subjects: 108 +/- 4%;
      HD patients: 103 +/- 4%; P: = NS). Acetylcholine (ACH 1:55 nmol/min; ACH 2:110;
      ACH 3:220), infused to stimulate endothelial NOS, had a significantly reduced
      effect in HD patients (control subjects: 246 +/- 32, 340 +/- 40, and 465 +/- 52%;
      HD patients: 251 +/- 55, 244 +/- 36, and 318 +/- 50%; P: = 0.002). N:-monomethyl
      L-arginine (LMA 1:1 micromol/min; LMA 2:2; LMA 3:4), given to block baseline NO
      generation, showed an enhanced response in HD patients (control subjects: 90 +/-
      2, 83 +/- 2, and 74 +/- 4%; HD patients: 84 +/- 3, 73 +/- 3, and 64 +/- 4%; P: =
      0.037). Vascular response to three doses of norepinephrine (60, 120, and 240
      pmol/min) was comparable in both groups, which indicated similar endothelium
      independent vasoconstriction. In summary, in normotensive HD patients, (1)
      vasodilation to defined doses of exogenous NO was reduced, (2) there was no
      evidence of substrate deficiency of NOS, and (3) stimulation of NOS was impaired;
      however, (4) baseline NO generation was increased. It is concluded that in HD
      patients, the NO system has a reduced capacity to regulate vascular tone and this
      impairment is most significant under conditions of NOS stimulation.

PMID- 10966500
TI  - Advanced glycation and lipoxidation end products: role of reactive carbonyl
      compounds generated during carbohydrate and lipid metabolism.

PMID- 10966499
TI  - Explained and unexplained ischemic heart disease risk after renal
      transplantation.
AB  - Whether the high incidence of ischemic heart disease (IHD) among renal transplant
      patients can be attributed to the same risk factors that have been identified in
      the general population is unclear. The risk for major IHD events occurring >1 yr
      after transplantation among 1124 transplant recipients was estimated by using the
      risk calculated from the Framingham Heart Study (FHS). The FHS risk predicted IHD
      (relative risk, 1.28; 95% confidence interval, 1.20 to 1.40; P: < 0.001);
      however, the FHS risk tended to underestimate the risk of IHD for renal
      transplant recipients. This was largely attributable to increased risks
      associated with diabetes mellitus and, to a lesser extent, age and cigarette
      smoking for renal transplant recipients. For men, the relative risks for diabetes
      mellitus were 2.78 (1.73 to 4.49) and 1.53 for the transplant recipient and FHS
      populations, respectively; the relative risks for age (in years) were 1.06 (1.04
      to 1.08) and 1.05, respectively, and those for smoking were 1.95 (1.20 to 3.19)
      and 1.69, respectively. For women, the relative risks for diabetes mellitus were
      5.40 (2.73 to 10.66) and 1.82, respectively. There was a tendency for the risk
      associated with cholesterol levels to be higher for transplant recipients,
      compared with the FHS population, but the risks associated with high-density
      lipoprotein cholesterol levels and BP appeared to be comparable. Independent of
      these and other risk factors, the adjusted risk of IHD for the transplant
      recipient population has decreased. Compared with the era before 1986,
      transplantation between 1986 and 1992 was associated with a lower relative risk
      of 0.60 (0.39 to 0.92); transplantation after 1992 was associated with an even
      lower relative risk of 0.27 (0.11 to 0.63) for IHD. Of concern was the fact that
      dihydropyridine calcium channel antagonists were associated with an increased
      risk for IHD (relative risk, 2.26; 95% confidence interval, 1.24 to 4.12; P: = 0.
      008), and this association was independent of other antihypertensive agents and
      risk factors. Therefore, although the FHS risk predicts IHD after renal
      transplantation, it tends to underestimate the risks, especially the risk
      associated with diabetes mellitus. The unexpected finding that dihydropyridine
      calcium channel antagonists were associated with an increased IHD risk merits
      further evaluation.

PMID- 10966501
TI  - Molecular genetics of nephronophthisis and medullary cystic kidney disease.
AB  - Nephronophthisis (NPH) and medullary cystic kidney disease (MCKD) constitute a
      group of renal cystic diseases that share the macroscopic feature of cyst
      development at the corticomedullary border of the kidneys. The disease variants
      also have in common a characteristic renal histologic triad of tubular basement
      membrane disintegration, tubular atrophy with cyst development, and interstitial
      cell infiltration with fibrosis. NPH and, in most instances, MCKD lead to chronic
      renal failure with an onset in the first two decades of life for recessive NPH
      and onset in adult life for autosomal dominant MCKD. There is extensive genetic
      heterogeneity with at least three different loci for NPH (NPHP1, NPHP2, and
      NPHP3) and two different loci for MCKD (MCKD1 and MCKD2). Juvenile
      nephronophthisis, in addition, can be associated with extrarenal organ
      involvement. As a first step toward understanding the pathogenesis of this
      disease group, the gene (NPH1) for juvenile nephronophthisis (NPH1) has been
      identified by positional cloning. Its gene product, nephrocystin, is a novel
      protein of unknown function that contains a src-homology 3 domain. It is
      hypothesized that the pathogenesis of NPH might be related to signaling processes
      at focal adhesions (the contact points between cells and extracellular matrix)
      and/or adherens junctions (the contact points between cells). This hypothesis is
      based on the fact that most src-homology 3-containing proteins are part of focal
      adhesion signaling complexes, on animal models that exhibit an NPH-like
      phenotype, and on the recent finding that nephrocystin binds to the protein
      p130(cas), a major mediator of focal adhesion signaling.

PMID- 10966503
TI  - Liver involvement in autosomal-dominant polycystic kidney disease: therapeutic
      dilemma.

PMID- 10966502
TI  - Nail-patella syndrome: identification of mutations in the LMX1B gene in Dutch
      families.
AB  - Nail-patella syndrome is an autosomal dominant disorder characterized by dyplasia
      of finger nails, skeletal anomalies, and, frequently, renal disease. It has
      recently been shown that this disorder is caused by putative loss-of-function
      mutations in a transcription factor (LMX1B) belonging to the LIM-homeodomain
      family, members of which are known to be important for pattern formation during
      development. A cohort of eight Dutch NPS families were screened for mutations in
      the LMX1B gene; seven different mutations, including one novel variant, were
      identified. Three of the mutations are very likely to result in truncated LMX1B
      proteins, three are predicted to influence sequence-specific DNA binding, and one
      is presumed to prevent the formation of a stable protein by abolishing the Zn(II)
      binding site of the protein. Although there was a remarkable high incidence of
      renal disease in one of the families, the nephropathy was not seen in all
      affected family members and the severity of renal impairment varied significantly
      among the patients. This indicates that the incidence and severity of nephropathy
      within this family cannot be attributed to the LMX1B genotype. In addition,
      evidence of a correlation between other characteristics of the NPS phenotype and
      specific mutations has not been found.

PMID- 10966504
TI  - The neurotoxicological consequences of developmental exposure to PCBs.
AB  - The articles highlighted in this issue are three reports by Kevin Crofton and
      colleagues dealing with neuromodulatory effects of PCB (Gilbert, Mundy, and
      Crofton, pp. 102-111; Roegge et al., pp. 121-130; and Crofton et al., pp. 131
      140).

PMID- 10966505
TI  - The distinction between genotoxic and epigenetic carcinogens and implication for
      cancer risk.

PMID- 10966506
TI  - The molecular effects of acrolein.
AB  - Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which
      humans are exposed in a variety of environmental situations, particularly as a
      component of smoke. In addition, as a metabolite of cyclophosphamide, acrolein is
      a major factor in the toxicity and perhaps the therapeutic activity of this
      important anticancer agent. The exposures to acrolein that are attained in vivo
      in most situations are quite low and the effects may differ from those seen at
      acutely toxic doses. At low doses, acrolein inhibits cell proliferation without
      causing cell death and may enhance apoptosis from secondary toxins, while at
      higher doses oncosis ensues. Although the acute toxicology of acrolein has been
      extensively investigated, both in animals and cultured cells, little information
      exists on the molecular effects of this reactive aldehyde. It is possible that
      the acrolein-mediated decrease in cell proliferation is caused by effecting
      changes in the expression of one or more growth- or stress-related genes or
      transcription factors secondary to a reduction in glutathione (GSH), which is
      rapidly depleted following acrolein treatment. It is apparent that the activation
      of the transcription factors nuclear factor kappa B (NF-kappa B) and activator
      protein 1 (AP-1) can be inhibited by acrolein. The purpose of this review is to
      assess the literature currently available on the molecular effects of acrolein,
      to discuss the relationship between effects on glutathione with those on various
      genes, and to present some new data showing that acrolein actively stimulates
      genes associated with the electrophile response element.

PMID- 10966507
TI  - Long circulating liposomes encapsulating organophosphorus acid anhydrolase in
      diisopropylfluorophosphate antagonism.
AB  - These studies are focused on antagonizing organophosphorous (OP) intoxications by
      a new conceptual approach using recombinant enzymes encapsulated within
      sterically stabilized liposomes to enhance diisopropylfluorophosphate (DFP)
      degradation. The OP hydrolyzing enzyme, organophosphorous acid anhydrolase
      (OPAA), encapsulated within the liposomes, was employed either alone or in
      combination with pralidoxime (2-PAM) and/or atropine. The recombinant OPAA
      enzyme, from the ALTEROMONAS: strain JD6, has high substrate specificity toward a
      wide range of OP compounds, e.g., DFP, soman, and sarin. The rate of DFP
      hydrolysis by liposomes containing OPAA (SL)* was measured by determining the
      changes in fluoride-ion concentration using a fluoride ion-selective electrode.
      This enzyme carrier system serves as a biodegradable protective environment for
      the OP-metabolizing enzyme (OPAA), resulting in an enhanced antidotal protection
      against the lethal effects of DFP. Free OPAA alone showed some antidotal
      protection; however, the protection with 2-PAM and/or atropine was greatly
      enhanced when combined with (SL)*.

PMID- 10966509
TI  - Analysis of rat liver foci growth with a quantitative two-cell model after
      treatment with 2,4,5,3',4'-pentachlorobiphenyl.
AB  - A biologically based, quantitative foci-growth model was used to analyze the
      effect of 20 and 52 weeks treatment with 2,4,5,3', 4'-pentachlorobiphenyl
      (PCB118) on the development of enzyme-altered foci in rat liver initiated with
      partial hepatectomy and diethylnitrosamine. Hepatocyte proliferation was examined
      and the data were used in the selection of division rates for the computer
      simulations of foci growth. The bromodeoxyuridine-labeling index in foci was
      generally larger than in nonfocal tissue. A strong correlation was found between
      foci occurrence and proliferation in focal as well as nonfocal tissue, suggesting
      that cytotoxicity and regenerative proliferation are involved in the foci growth
      caused by PCB118. The foci growth model adequately simulated the foci data when
      certain assumptions were introduced. Given the general view that PCB118 is a
      nonmutagenic compound, the foci data could not be modeled assuming one
      homogeneous cell population, but was adequately fitted assuming two separate
      initiated cell populations that respond differently to the promotion stimulus.
      Other assumptions were a selective growth advantage for initiated cells during
      and shortly after the initiation treatment, and a transient increase of
      proliferation in focal hepatocytes at the first PCB administration in the higher
      dose groups. The model predicted an increased rate of focal cell death, at high
      doses, to adequately fit the foci data. These assumptions are supported by
      experimental data for other carcinogens, indicating the importance of studying
      cell kinetics in heterogeneous subpopulations of initiated cells in PCB-induced
      hepatocarcinogenesis.

PMID- 10966508
TI  - Effects of arsenic-, platinum-, and gold-containing drugs on the disposition of
      exogenous selenium in rats.
AB  - Having found that the electrophilic model compound sulfobromophthalein markedly
      altered the fate of exogenous selenium in the body by reacting in vivo with
      nucleophilic selenium metabolites, the effects of metal-containing drugs with
      expected selenium reactivity were tested on biliary, urinary, and pulmonary
      excretion. Tissue distribution of selenium in selenite-injected rats was also
      examined. Coadministration with [(75)Se]selenite (10 micromol/kg, iv) of the
      trypanosomicid arsenicals (100 micromol/kg, iv) trimelarsan (TMA) or melarsoprol
      (MAP), the antitumor cisplatin (25 micromol/kg, iv), or the antirheumatic gold
      sodium thiomalate (25 or 50 micromol/kg, iv) significantly altered the
      disposition of (75)Se, whereas carboplatin (100 micromol/kg, iv) did not produce
      such an effect. The most dramatic alterations included the approximately 20-fold
      increase in the biliary excretion rate of selenium in response to TMA and MAP,
      the almost complete cessation of the exhalation of selenium as dimethyl selenide
      after administration of the arsenic- and gold-containing drugs, and the manifold
      accumulation of selenium in the blood plasma following gold injection. Direct
      chemical reaction of the drugs with nucleophilic selenite metabolites in the body
      may underlie these alterations. The tight coordination in time and extent
      observed between the biliary excretion of arsenic and selenium in rats receiving
      either of the arsenicals and selenite supports this hypothesis. However, attempts
      to detect selenium-containing biliary metabolites of TMA and MAP have failed,
      possibly owing to their instability. In summary, the arsenic-, platinum- and gold
      containing drugs significantly influence the fate of exogenous selenium, whereby
      they may adversely affect the availability of this essential element for
      synthesis of selenoenzymes. Furthermore, the capability of TMA and MAP to enhance
      the biliary and total excretion of selenium renders these drugs significant
      candidates for antidotes in selenium intoxication.

PMID- 10966510
TI  - Evaluation of in vitro reporter gene induction assays for use in a rapid
      prescreen for compound selection to test specificity in the Tg.AC mouse short
      term carcinogenicity assay.
AB  - Under ICH guidelines, short-term carcinogenicity assays such as the Tg.AC assay
      are allowed alternatives for one species in the 2-year rodent bioassay. The Tg.AC
      transgenic mouse, which carries the v-Ha-ras oncogene under control of the zeta
      globin promoter, develops skin papillomas in response to dermal application of
      carcinogens and tumor promoters. The appropriate specificity of the Tg.AC model
      for testing pharmaceuticals has not been systematically evaluated. The selection
      of candidate test compounds among noncarcinogenic pharmaceuticals would be aided
      by a high-throughput in vitro prescreen correlative of activity in the in vivo
      Tg.AC assay. Here we describe the development of a prescreen based on correct
      response to 24 compounds tested previously in Tg.AC mice. The in vitro
      prescreens, chosen to reflect molecular pathways possibly involved in Tg.AC
      papilloma formation, consisted of a zeta-globin promoter-luciferase construct
      stably expressed in K562 cells (Zeta-Luc) and three of the stress-response
      element-chloramphenicol acetyltransferase (CAT) fusion constructs stably
      expressed in HepG2 cells that are part of the CAT-Tox (L)iver assay. The stress
      response elements chosen were the c-fos promoter, the gadd153 promoter, and p53
      response element repeats. Of the four assays, the gadd153-CAT assay showed the
      strongest concordance with activity in the Tg.AC assay, correctly classifying 78%
      of Tg.AC positive and 83% of Tg.AC negative compounds. The correlation was
      further improved by adding the Zeta-Luc assay as a second-stage screen. These
      cell-based assays will be used in a novel approach to selecting candidate
      compounds that challenge the specificity of the Tg.AC assay toward
      pharmaceuticals.

PMID- 10966511
TI  - Lack of significant estrogenic or antiestrogenic activity of pyrethroid
      insecticides in three in vitro assays based on classic estrogen receptor alpha
      mediated mechanisms.
AB  - Estrogenic and antiestrogenic activity of pyrethroid insecticides (d-trans
      allethrin, cypermethrin, empenthrin, fenvalerate, imiprothrin, permethrin, d
      phenothrin and prallethrin) was evaluated using a suite of three in vitro assays
      based on classic human estrogen receptor alpha (hER alpha)-mediated mechanisms. A
      mammalian cell-based luciferase reporter gene assay was developed for examining
      effects on hER alpha-mediated gene activation. hER alpha-independent effects on
      the gene activation were examined using control cells with constitutive
      luciferase activation by a herpes simplex virus thymidine kinase (HSV-TK)
      promoter for determining appropriate dose levels of test chemicals. Moreover, the
      test chemical-dependent interaction between hER alpha and a coactivator
      (transcriptional intermediary factor 2: TIF2) was analyzed by a yeast two-hybrid
      method, competitive binding to hER alpha being assayed by a fluorescence
      polarization method. Significant (p < 0.05) positive effects of estrogenic
      substances (E2/estradiol, diethylstilbestrol, and p-nonylphenol) were detected in
      all assays. An antiestrogen, 4-hydroxytamoxifen, significantly inhibited E2
      mediated transactivation and interaction between hER alpha and TIF2 through hER
      alpha binding (p < 0.05). However, none of the pyrethroids tested showed
      significant (p < 0.05) estrogenic or antiestrogenic effects (100 nM-10 microM),
      indicating that they do not impact on the classic hER alpha-mediated activation
      pathway in vitro.

PMID- 10966513
TI  - Oral bioavailability and pharmacokinetics of elimination of 9
      hydroxybenzo[a]pyrene and its glucoside and sulfate conjugates after
      administration to male and female American lobsters, Homarus americanus.
AB  - The pharmacokinetics of [(3)H]-9-hydroxybenzo[a]pyrene (9-OH-BaP), a highly
      lipophilic primary metabolite of benzo(a)pyrene, were examined after
      intrapericardial (iv) or oral doses of 50 or 200 microg/kg to intermolt American
      lobsters, Homarus americanus. Combining data for all lobsters, the average
      terminal elimination half-life of parent 9-OH-BaP was 97.3 h after iv and 56.5 h
      after oral administration, considerably less than found previously for
      benzo(a)pyrene (720 h). The oral bioavailability of parent 9-OH-BaP, calculated
      from the area under the hemolymph concentration curve, was 15.9%. The low
      bioavailability and variable elimination rates were attributed to extensive first
      pass conjugation and sequestration in the hepatopancreas. BaP-9-sulfate was the
      major metabolite. Hemolymph concentrations of BaP-9-sulfate increased up to one
      day after the dose, and then decreased, with a terminal elimination half-life of
      45 h. BaP 9-beta-D-glucoside was a minor metabolite in most hemolymph and tissue
      samples; an exception was hemolymph from the iv high-dose group. Concentrations
      of 9-OH-BaP and metabolites in the edible muscle tissue were similar to those in
      hemolymph, and 9-OH-BaP residues at 10 to 16 days after the dose were 3 to 12
      ng/g muscle. Sulfotransferase and UDP-glucosyltransferase (UGT) activities with 9
      OH-BaP were found in the antennal gland, intestinal mucosa, and hepatopancreas
      (UGT only). Sulfatase activity with BaP-9-sulfate, found in both the
      hepatopancreas and the antennal gland, was thought to contribute to metabolite
      cycling. These studies showed that 9-OH-BaP was readily conjugated to sulfate and
      glucose in the lobster, and that despite their high lipophilicity, 9-OH-BaP and
      conjugates were excreted from the lobster hemolymph and tissues much more rapidly
      than benzo[a]pyrene.

PMID- 10966512
TI  - A 90-day drinking water toxicity study in rats of the environmental contaminant
      ammonium perchlorate.
AB  - Perchlorate (ClO(4)(-)), the dissociated anion of perchlorate salts such as
      ammonium, potassium, and sodium perchlorate, has been recently recognized as a
      persistent and pervasive contaminant of drinking water supplies in a number of
      metropolitan areas. Perchlorate is of concern because of uncertainties in the
      toxicological database available to address the potential human health effects of
      low-level exposure. The purpose of this study was to evaluate the subchronic
      toxicity of perchlorate when administered to Sprague-Dawley rats as ammonium
      perchlorate (AP) for 14 or 90 days. The study consisted of an untreated control
      group and five treatment groups that received continuous exposure to AP via the
      drinking water at dosage levels of 0.01, 0.05, 0.2, 1.0, and 10.0 mg/kg/day. The
      study design included a nontreatment recovery period of 30 days to evaluate the
      reversibility of any AP-induced effects at the 0.05, 1.0, and 10.0 mg/kg/day
      levels. The study also investigated the potential effects of AP on male sperm
      parameters, female estrous cyclicity, bone marrow micronucleus formation, and
      serum hormone levels, i.e., triiodothyronine (T(3)), thyroxine (T(4)), and
      thyroid stimulating hormone (TSH). No toxicologically meaningful differences were
      observed between the control and AP-treated groups with respect to survival,
      clinical observations, body weights, food consumption, water consumption,
      ophthalmology, hematology, clinical chemistry, estrous cycling, sperm parameters,
      or bone marrow micronucleus formation. A target organ effect was produced by AP
      in the thyroids of male and female rats at the 10 mg/kg/day level after 14 and 90
      days of exposure. The effect was characterized by significantly increased thyroid
      weights and thyroid histopathology consisting primarily of follicular cell
      hypertrophy with microfollicle formation and colloid depletion. These changes
      were reversible after a nontreatment recovery period of 30 days. Statistically
      significant changes in TSH and thyroid hormones were observed at all AP dosage
      levels tested; however, no thyroid organ weight or histopathological effects were
      observed at AP dosage levels < or = 1.0 mg/kg/day. In the absence of thyroid
      organ weight and histopathological effects, the toxicological significance of TSH
      and thyroid hormone changes at AP dosage levels < or = 1.0 mg/kg/day remains to
      be determined.

PMID- 10966514
TI  - The efficiency of maternal transfer of lead and its influence on plasma IgE and
      splenic cellularity of mice.
AB  - Exposure to the well known environmental toxicant lead is typically assessed by
      blood and/or bone levels and has been implicated in the onset of a variety of
      diseases affecting multiple human systems. However, there are conflicting data
      regarding the efficiency of in utero versus lactational transfer of lead to
      offspring, and the immunomodulatory effects of lead in early life have not been
      well defined. Pregnant BALB/c mice were exposed to lead acetate in their drinking
      water beginning at approximately day 15 of gestation, and cross-fostering of
      exposed/nonexposed litters was performed at parturition. Significant increases of
      blood lead levels of all exposed offspring were found at 1 week of age with
      evidence for both transplacental and lactational transfer. Additionally, mice
      exposed to lead continuously beginning at approximately 6 days prior to birth
      showed significant decreases in their blood lead levels 2 weeks after weaning,
      despite continued exposure as adults. This result suggests maternal transfer of
      lead is more efficient than oral adult exposure and that substantial lead
      transfer occurs both transplacentally and lactationally. The incidence of
      childhood atopic responses including asthma has risen considerably in recent
      years, particularly within areas containing higher levels of environmental
      pollutants. Plasma IgE levels of 2-week-old neonates exposed to lead before
      and/or after birth were measured as an index of atopy. Neonates exposed to lead
      transplacentally and/or lactationally had significantly higher plasma IgE levels,
      a biomarker of atopy, and lower splenic white blood cell numbers than age-matched
      controls. These results resemble the lag in immunocompetency and increase in
      serum IgE noted in atopic children and suggest a role for environmental toxicants
      and non-allergen-specific immunology in the prevalence of atopy and asthma in
      children.

PMID- 10966515
TI  - A dose-response study of ibogaine-induced neuropathology in the rat cerebellum.
AB  - Ibogaine (IBO) is an indole alkaloid from the West African shrub, Tabernanthe
      iboga. It is structurally related to harmaline, and both these compounds are
      rigid analogs of melatonin. IBO has both psychoactive and stimulant properties.
      In single-blind trials with humans, it ameliorated withdrawal symptoms and
      interrupted the addiction process. However, IBO also produced neurodegeneration
      of Purkinje cells and gliosis of Bergmann astrocytes in the cerebella of rats
      given even a single dose (100 mg/kg, ip). Here, we treated rats (n = 6 per group)
      with either a single ip injection of saline or with 25 mg/kg, 50 mg/kg, 75 mg/kg,
      or 100 mg/kg of IBO. As biomarkers of cerebellar neurotoxicity, we specifically
      labeled degenerating neurons and axons with silver, astrocytes with antisera to
      glial fibrillary acidic protein (GFAP), and Purkinje neurons with antisera to
      calbindin. All rats of the 100-mg/kg group showed the same pattern of cerebellar
      damage previously described: multiple bands of degenerating Purkinje neurons. All
      rats of the 75-mg/ kg group had neurodegeneration similar to the 100-mg/kg group,
      but the bands appeared to be narrower. Only 2 of 6 rats that received 50 mg/kg
      were affected; despite few degenerating neuronal perikarya, cerebella from these
      rats did contain patches of astrocytosis similar to those observed with 75 or 100
      mg/kg IBO. These observations affirm the usefulness of GFAP immunohistochemistry
      as a sensitive biomarker of neurotoxicity. None of the sections from the 25-mg/kg
      rats, however stained, were distinguishable from saline controls, indicating that
      this dose level may be considered as a no-observable-adverse-effect level
      (NOAEL).

PMID- 10966516
TI  - Spatial learning and long-term potentiation in the dentate gyrus of the
      hippocampus in animals developmentally exposed to Aroclor 1254.
AB  - Developmental exposure to polychlorinated biphenyls (PCBs) has been associated
      with cognitive deficits in children. Rodent studies have revealed impairments in
      learning tasks involving the hippocampus. The present study sought to examine
      hippocampal synaptic plasticity in the dentate gyrus and spatial learning in
      animals exposed to PCBs early in development. Pregnant Long-Evans rats were
      administered either corn oil (control) or 6 mg/kg/day of a commercial PCB
      mixture, Aroclor 1254 (A1254) by gavage from gestational day (GD) 6 until pups
      were weaned on postnatal day (PND) 21. Spatial learning was assessed at 3 months
      of age in male and female offspring using the Morris water maze. Latency to find
      a hidden platform that remained in the same position over 20 days of testing did
      not differ between control and PCB-exposed groups. Neither were group differences
      evident in a repeated acquisition version of the task in which the platform
      remained in the same position over the 2 daily trials but was moved to a new
      spatial location each day. Male littermates of animals in the behavioral study
      were tested electrophysiologically at 5-7 months of age. Field potentials evoked
      by perforant path stimulation were recorded in the dentate gyrus under urethane
      anesthesia. Input/output (I/O) functions were assessed by averaging the response
      evoked in the dentate gyrus to stimulus pulses delivered to the perforant path in
      an ascending intensity series. Long-term potentiation (LTP) was induced by
      delivering a series of brief, high-frequency train bursts to the perforant path
      at increasing stimulus intensities, and I/O functions were reassessed 1 h later.
      No differences in baseline synaptic population spike (PS) and excitatory
      postsynaptic potential (EPSP) slope amplitudes were discerned between the groups
      prior to train delivery. Post-train I/O functions, however, revealed a decrement
      in the magnitude of evoked LTP in PCB-exposed animals, and an increase in the
      train intensity required to induce LTP. The observed dissociation between
      impaired hippocampal plasticity, in the absence of a detectable deficit in
      performance of a hippocampal-dependent task, may be due to task complexity, the
      maintenance of some degree of plasticity in the PCB-exposed animals, or the
      possibility that intact dentate gyrus LTP may not be requisite for water-maze
      learning.

PMID- 10966517
TI  - Acute sarin exposure causes differential regulation of choline acetyltransferase,
      acetylcholinesterase, and acetylcholine receptors in the central nervous system
      of the rat.
AB  - Acute neurotoxic effects of sarin (O:-isopropylmethylphosphonoflouridate) in male
      Sprague-Dawley rats were studied. The animals were treated with intramuscular
      (im) injections of either 1 x LD(50) (100 microg/kg), and sacrificed at 0. 5, 1,
      3, 6, 15, or 20 h after treatment, or with im injections of either 0.01, 0.1,
      0.5, or 1 x LD(50) and sacrificed 15 h after treatment. Plasma
      butyrylcholinesterase (BChE) and brain regional acetylcholinesterase (AChE) were
      inhibited (45-55%) by 30 min after the LD(50) dose. BChE in the plasma and AChE
      in cortex, brainstem, midbrain, and cerebellum remained inhibited for up to 20 h
      following a single LD(50) treatment. No inhibition in plasma BChE activity was
      observed 20 h after treatment with doses lower than the LD(50) dose. Midbrain and
      brainstem seem to be most responsive to sarin treatment at lower doses, as these
      regions exhibited inhibition (approximately 49% and 10%, respectively) in AChE
      activity following 0.1 x LD(50) treatment, after 20 h. Choline acetyltransferase
      (ChAT) activity was increased in cortex, brainstem, and midbrain 6 h after LD(50)
      treatment, and the elevated enzyme activity persisted up to 20 h after treatment.
      Cortex ChAT activity was significantly increased following a 0.1 x LD(50) dose,
      whereas brainstem and midbrain did not show any effect at lower doses. Treatment
      with an LD(50) dose caused a biphasic response in cortical nicotinic
      acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (m2-mAChR)
      ligand binding, using [(3)H]cytisine and [(3)H]AFDX-384 as ligands for nAChR and
      mAChR, respectively. Decreases at 1 and 3 h and consistent increases at 6, 15,
      and 20 h in nAChR and m2-mAChR were observed following a single LD(50) dose. The
      increase in nAChR ligand binding densities was much more pronounced than in
      mAChR. These results suggest that a single exposure of sarin, ranging from 0.1 to
      1 x LD(50), modulates the cholinergic pathways differently and thereby causes
      dysregulation in excitatory neurotransmission.

PMID- 10966518
TI  - Gestational-lactational exposure to Aroclor 1254 impairs radial-arm maze
      performance in male rats.
AB  - Developmental exposure to polychlorinated biphenyls (PCBs) has been associated
      with cognitive deficits in children. The current study assessed effects of
      gestational and lactational exposure to a commercial PCB mixture, Aroclor 1254
      (A1254), on spatial learning and memory in rats, using the radial-arm maze (RAM).
      Pregnant Long-Evans females (10/dose group) were exposed to 0 or 6-mg/kg/day
      A1254 (po in corn oil) from gestation day (GD) 6 to weaning at postnatal day
      (PND) 21. After they reached adulthood, 1 male and 1 female from each litter were
      tested on a working/reference memory task using a 12-arm RAM. Eight of the 12
      arms were baited, with the pattern of baited arms remaining the same on every
      trial for each rat. Compared to control males, the A1254-exposed males made
      significantly more working memory errors (2.15 +/- 0.13 and 3.20 +/- 0.18 errors
      +/- SEM for control and A1254 males, respectively) and reference memory errors
      (3.17 +/- 0.10 and 4.13+/-0.14 errors +/- SEM for control and A1254 males,
      respectively) on the RAM. In contrast, A1254-exposed females were not impaired
      relative to control females on the RAM. Drug challenges with dizocilpine (MK-801)
      and scopolamine did not differentially affect working or reference memory of
      control and exposed rats. These data suggest that perinatal exposure to A1254 may
      cause sex-specific deficits in spatial learning and memory, and that NMDA
      mediated and muscarinic neurotransmission, as assessed with the drug challenges,
      were not markedly impaired in the A1254-exposed animals.

PMID- 10966519
TI  - PCBs, thyroid hormones, and ototoxicity in rats: cross-fostering experiments
      demonstrate the impact of postnatal lactation exposure.
AB  - Previous research has demonstrated the sensitivity of the developing rat to the
      hypothyroxinemic and ototoxic effects of perinatal exposure to Aroclor 1254
      (A1254). We tested the hypothesis that postnatal exposure via lactation is the
      major cause of the ototoxicity by cross fostering animals at birth. Primiparous
      rats (22-24/dose) received 0 or 6 mg/kg A1254 (po in corn oil) from gestation day
      (GD) 6 to postnatal day (PND) 21. On the day of birth, half of the treated
      litters and half of the control litters were cross-fostered, resulting in the
      following groups: Ctrl/Ctrl (controls); A1254/A1254 (perinatal exposure);
      A1254/Ctrl (prenatal exposure only); and Ctrl/A1254 (postnatal exposure only). We
      assessed offspring at a number of ages for: serum thyroid hormone concentrations,
      liver and brain concentrations of PCBs, body weight, mortality, age of eye
      opening, auditory startle amplitudes, and auditory thresholds for 1 kHz and 40
      kHz tones. Circulating thyroxine (T(4)) concentrations were sharply reduced at GD
      21 in the A1254-exposed group, and on PND 3, 7, 14, and 21 in the A1254/A1254 and
      the Ctrl/A1254 groups. Smaller decreases in T(4) were observed in the A1254/Ctrl
      group on PND 3, 7, and 14. PCB concentrations in the liver on PND 21 were sharply
      elevated in the A1254/A1254 and Ctrl/A1254 groups. Much smaller increases were
      seen in the A1254/Ctrl group. Age of eye-opening and startle amplitudes were
      unaffected by treatment. A1254 exposure caused permanent hearing deficits (20 dB
      increase) at the low frequency (1 kHz) in the A1254/A1254 and Ctrl/A1254 groups.
      The present findings demonstrated that the critical period for the ototoxicity of
      developmental A1254 exposure is within the first few postnatal weeks in the rat.
      This effect is consistent with the greater degree of postnatal hypothyroxinemia
      resulting from the greater magnitude of exposure that occurs postnatally via
      lactation.

PMID- 10966520
TI  - Modulation of glutathione and glutamate-L-cysteine ligase by methylmercury during
      mouse development.
AB  - The antioxidant tripeptide glutathione has been proposed to be important in
      defense against oxidative stress and heavy metal toxicity. We evaluated
      alterations in glutathione regulation and synthesis associated with low-level
      chronic methylmercury (MeHg) exposure in the developing mouse fetus. Female
      C57Bl/6 mice were given 0, 3, or 10 ppm MeHg in the drinking water for 2 weeks
      prior to breeding and throughout pregnancy. Fetuses were collected on gestational
      days (gd) 12 and 16. Total glutathione, reduced glutathione (GSH), oxidized
      glutathione (GSSR), and glutamate-L-cysteine ligase (Glcl) activity were assessed
      in yolk sacs and fetuses at gd 16. Western and Northern blots for Glcl-catalytic
      (Glclc) and Glcl-regulatory (Glclr) subunits were performed on gd 12 and gd 16
      fetuses. There were no changes in total glutathione in gd 16 mouse fetuses with
      exposure, but there were dose-related decreases in GSH and increases in GSSR. In
      contrast, visceral yolk sacs exhibited an increase in total glutathione in the
      low-dose groups, but no changes in the high-dose group. There were no changes in
      Glcl activity in fetuses, but there was a 2-fold increase in Glcl activity in
      yolk sacs from both low-dose and high-dose groups. There was a 2-fold induction
      in GLCLC: mRNA and protein in the gd 16 yolk sacs at both 3 and 10 ppm MeHg. No
      treatment-related changes in Glclr protein in either gd 12 or gd 16 yolk sacs or
      fetuses were found. Thus, the yolk sac is capable of up-regulating Glclc and GSH
      synthetic capacity in response to MeHg exposure. This increase appears to be
      sufficient to resist MeHg-induced GSH depletion in the yolk sac; however fetal
      glutathione redox status is compromised with exposure to 10 ppm MeHg.

PMID- 10966521
TI  - Induction of testosterone biotransformation enzymes following oral administration
      of methyl tert-butyl ether to male Sprague-Dawley rats.
AB  - Methyl tert-butyl ether (MTBE) is an oxygenated fuel additive used to decrease
      carbon monoxide emissions during gasoline combustion. In the current study, we
      investigated the hypothesis that the MTBE-induced decrease in serum testosterone
      levels in male rats may be due in part to the ability of MTBE to induce the
      metabolism of endogenous testosterone and hence enhance its clearance. Nine-week
      old male Sprague-Dawley rats were gavaged with 250, 500, 1000, or 1500 mg
      MTBE/kg/day in corn oil or corn oil alone for 15 or 28 consecutive days.
      Increased relative liver weight (10-14%) and minimal-to-moderate centrilobular
      hypertrophy were observed in rats treated with 1000 and 1500 mg MTBE/kg/day (high
      doses) for 28 days. Total hepatic microsomal cytochrome P450 (CYP) was increased
      1. 3-fold in the high-dose, 15-day-treated rats. An evaluation of specific CYP
      activities using selective markers demonstrated a 2. 0-fold increase in CYP2B1/2
      in rats treated with 1000 mg MTBE/kg/day for 28 days, and with 1500 mg
      MTBE/kg/day for 15 and 28 days (6.5- and 2.9-fold, respectively). CYP1A1/2,
      CYP2A1, and CYP2E1 activities were increased 1.5-, 2.4-, and 2.3-fold,
      respectively, in high-dose, 15-day-treated rats. CYP2E1 was also increased in
      high-dose, 28-day-treated rats (2.0-fold). CYP3A1/2 was increased 2.1-fold and
      UDP-glucuronosyltransferase activity 1.7-fold in high-dose, 28-day-treated rats.
      MTBE also induced its own metabolism 2.1-fold in high-dose, 28-day-treated rats.
      Results indicate that MTBE induces selected enzymes involved in testosterone
      metabolism. The decrease in serum testosterone observed following MTBE
      administration may be the result of enhanced testosterone metabolism and
      subsequent clearance.

PMID- 10966522
TI  - Cadmium decreases gap junctional intercellular communication in mouse liver.
AB  - Cadmium (Cd) is an environmental pollutant of increasing importance, due to
      industrialization, smoking, and the lack of effective therapy for Cd poisoning.
      The general population is exposed to Cd principally through food and water. The
      metal accumulates slowly in the liver and kidney, the target organs of acute and
      chronic Cd toxicity, respectively. We showed recently that liver is also a target
      organ for chronic Cd toxicity. Gap junctional intercellular communication (GJIC)
      is a means of maintaining cellular homeostasis in multicellular organisms. It
      involves the transfer of small, water-soluble molecules through intercellular
      channels (gap junctions), composed of proteins called connexins. The major
      connexins of liver (hepatocytes) are connexin 32 (Cx32) and connexin 26 (Cx26).
      Cd disrupts cellular homeostasis in the liver through its induction of necrosis,
      apoptosis, and cellular proliferation. It is to be expected, therefore, that Cd
      must exert some effect on GJIC. This study investigates Cd-induced alterations in
      GJIC, Cx32, and Cx26 expression, and in cytoskeletal actin, and relates the
      changes to apoptosis and cell proliferation induced by Cd in vivo. Mice were
      injected ip with 30 micromol Cd/kg, and were observed for up to 48 h. Other
      groups of mice were injected with 5-60 micromol Cd/kg and observed for 9 h. Blood
      and liver were harvested and used for analysis of GJIC, connexin expression,
      cytoskeletal actin, serum enzymes, and liver pathology. Cd produced a time- and
      dose-dependent inhibition of GJIC in liver, along with parallel decreases in the
      expression of Cx32 and Cx26. Cd also produced disruption and loss of cytoskeletal
      actin in liver in a time- and dose-dependent manner. These observations are
      discussed in relation to the toxicity of Cd, and possible mechanisms of induction
      of the GJIC-related alterations are presented.

PMID- 10966523
TI  - Metallothionein-I/II null mice are sensitive to chronic oral cadmium-induced
      nephrotoxicity.
AB  - Chronic exposure to cadmium (Cd) via food and drinking water is a major human
      health concern. We have previously shown that metallothionein (MT), a metal
      binding protein, plays an important role in protecting against Cd toxicity
      produced by repeated sc injections. However, it is unclear whether MT protects
      against Cd-induced nephrotoxicity following chronic oral exposure, a route with
      obvious human relevance. To clarify this issue, MT-I/II knockout (MT-null) and
      background-matched wild-type (WT) mice were allowed free access to drinking water
      containing CdCl(2) (30, 100, and 300 ppm Cd), or feed containing CdCl(2) (100 ppm
      Cd) for 6 months, and the resultant nephrotoxicity was examined. Chronic oral Cd
      exposure produced a dose-dependent accumulation of Cd in liver and kidney of WT
      mice, reaching levels up to 50 microg Cd/g tissue. Immunohistological
      localization of renal MT indicated that chronic oral Cd exposure in WT mice
      greatly increased MT in the proximal tubules and the medulla, with cellular
      localization in both the cytoplasm and nuclei. As expected, no MT was detected in
      kidneys of MT-null mice. After 6 months of Cd exposure, tissue Cd concentrations
      in MT-null mice were only about one-fifth of that in WT mice. Even though the
      renal Cd concentrations were much lower in the MT-null mice, they were more
      sensitive than WT mice to Cd-induced renal injury, as evidenced by more severe
      nephropathic lesions, increased urinary excretion of gamma-glutamyl-transferase
      and glucose, and elevated blood urea nitrogen. Six months of Cd exposure to MT
      null animals resulted in greater increases in renal caspase-3 activity, an
      indicator of apoptosis, than to WT mice. In conclusion, this study demonstrates
      that lack of MT renders MT-null mice vulnerable to Cd-induced nephrotoxicity
      after chronic oral exposure, the primary route of human Cd exposure.

PMID- 10966524
TI  - Bile acids affect liver mitochondrial bioenergetics: possible relevance for
      cholestasis therapy.
AB  - It has been pointed out that intracellular accumulation of bile acids cause
      hepatocyte injury in cholestatic disease process. This study was aimed to test if
      cytotoxicity of these compounds is mediated through mitochondria dysfunction.
      Bile acids effects on isolated rat liver mitochondrial were analyzed by
      monitoring changes in membrane potential and mitochondrial respiration, as well
      as alterations in H(+) membrane permeability and mitochondrial permeability
      transition pore induction. Increasing concentrations of the bile acids litocholic
      (LCA), deoxycholic (DCA), ursodeoxycholic (UDCA), chenodeoxycholic (CDCA),
      glycochenodeoxycholic (GCDC), or taurochenodeoxycholic (TCDC) decrease
      transmembrane potential (delta psi) developed upon succinate energization. These
      compounds also decreased state 3 respiration and enhanced state 4. We have also
      demonstrated that the observed concentration-dependent stimulation of state 4 by
      LCA, DCA, CDCA, TCDC, and GCDC, is associated with an enhanced permeability of
      mitochondria to H(+). Addition of LCA, DCA, CDCA, TCDC, GCDC, and UDCA to
      mitochondria energized with succinate resulted in a dose-dependent membrane
      depolarization and stimulation of mitochondrial permeability transition.
      Tauroursodeoxycholate (TUDC) elicited no significant effect on succinate
      supported mitochondrial bioenergetics. In contrast, in the presence of
      glycoursodeoxycholic (GUDC), delta psi increases as a function of bile salt
      concentration. The results of this investigation demonstrate that at
      toxicologically relevant concentrations, most but not all bile acids alter
      mitochondrial bioenergetics, so impairment of mitochondrial function can be
      clinically relevant for patients with cholestasis.

PMID- 10966525
TI  - Re: Long-term toxicity and carcinogenicity study of cyclamate in nonhuman
      primates (Takayama et al., Toxicol. Sci. 53, 33-39)

PMID- 10966527
TI  - The prothrombotic state in atrial fibrillation: new insights, more questions, and
      clear answers needed.

PMID- 10966526
TI  - Preventing neurologic complications in coronary artery surgery: the "off-pump, no
      touch" technique.

PMID- 10966528
TI  - Cardiac marker testing: where should we focus?

PMID- 10966529
TI  - Clopidogrel instead of ticlopidine after coronary stent placement: is the switch
      justified?

PMID- 10966530
TI  - Should we measure health-related quality of life?

PMID- 10966531
TI  - Rationale for the use of combination angiotensin-converting enzyme
      inhibitor/angiotensin II receptor blocker therapy in heart failure.
AB  - BACKGROUND: Heart failure (HF) is a major cause of morbidity and mortality in the
      United States. The renin-angiotensin system (RAS) plays a major role in its
      pathophysiology, and angiotensin-converting enzyme (ACE) inhibitors are the
      cornerstone of therapy. However, HF continues to progress despite this therapy,
      perhaps because of production of angiotensin II by alternative pathways, which
      lead to direct stimulation of the angiotensin II receptor. Angiotensin II
      receptor blocker (ARB) therapy alone or in combination with the ACE inhibitor is
      a promising approach to block the RAS and slow HF progression more completely.
      METHODS: The current medical literature on the pathophysiology of HF and the use
      of ACE inhibitors and ARBs was extensively reviewed. RESULTS: Evidence from basic
      science, experimental animals, and clinical trials provides data on the safety
      and efficacy of RAS inhibition with ACE inhibitors and ARBs as monotherapy and in
      combination. Data from the Evaluation of Losartan in the Elderly (ELITE) II trial
      indicate that ARBs alone do not appear to be more effective than ACE inhibitors
      in HF, but studies evaluating their use in combination are currently ongoing.
      CONCLUSIONS: The addition of an ARB offers more complete angiotensin II receptor
      blockade of the RAS than can be obtained by ACE inhibitors alone. Combination
      therapy preserves the benefits of bradykinin potentiation offered by ACE
      inhibitors while providing potential antitrophic influences of AT(2) receptor
      stimulation and may play an increased role in the treatment of chronic HF in the
      future.

PMID- 10966532
TI  - Randomized trial of sertraline in patients with unexplained chest pain of
      noncardiac origin.
AB  - BACKGROUND: Between 10% and 30% of patients with symptoms similar to angina and
      sufficient to justify cardiac catheterization are found to have normal coronary
      angiograms. Treatment of patients with chest pain with no apparent cardiac cause
      is a major clinical problem. Our hypothesis was that sertraline would reduce the
      severity of pain in patients with chest pain of noncardiac origin. METHODS AND
      RESULTS: This was a single-site, double-blind, placebo-controlled study of the
      efficacy, tolerability, and safety of sertraline in the treatment of noncardiac
      chest pain in outpatients. Thirty patients were enrolled in the study. After 1
      week of single-blind placebo washout, patients were randomly assigned in a double
      blind fashion either to drug or placebo. The Beck Depression Inventory was
      administered at baseline and at completion of study. Daily pain diaries (visual
      analogue scale, rating pain on a scale of 1 to 10) were selfadministered and
      evaluated at baseline and at follow-up visits. Statistical measures were
      performed with an intention-to-treat approach. Patients who received sertraline
      over the course of the study showed a statistically significant reduction in pain
      compared with those who were receiving placebo. CONCLUSIONS: The use of
      sertraline in patients with noncardiac chest pain produced clinically significant
      reduction of daily pain. These results suggest the need for further studies of
      the efficacy and tolerability of sertraline and other selective serotonin
      reuptake inhibitors in the long-term management of noncardiac chest pain.

PMID- 10966533
TI  - Very early risk stratification after thrombolytic therapy with a bedside
      myoglobin assay and the 12-lead electrocardiogram.
AB  - BACKGROUND: Available clinical criteria to estimate prognosis in patients with
      evolving ST-segment elevation myocardial infarction do not consider the impact of
      reperfusion therapy and do not incorporate measurement of baseline levels of
      cardiac serum markers. We evaluated the combination of a baseline myoglobin assay
      and early (60- to 90-minute) ST resolution for risk stratification after ST
      segment elevation myocardial infarction. METHODS: In a prospective substudy of
      the Intravenous nPA for Treatment of Infarcting Myocardium Early-II (InTIME-II)
      trial carried out in 2079 patients, a rapid qualitative assay for myoglobin was
      performed immediately before thrombolysis. Serial 12-lead electrocardiograms were
      performed at baseline and 60 to 90 minutes after thrombolysis. ST resolution was
      categorized as complete (>/=70%), partial (30% to <70%), or none (<30%). RESULTS:
      Mortality rate at 30 days was 3.3% in the 905 patients with a negative baseline
      myoglobin assay versus 8.9% in the 527 patients with a positive assay (P <.0001).
      Mortality rate was lowest (2.4%) among the 614 patients with complete ST
      resolution, intermediate (4.9%) among the 512 patients with partial ST
      resolution, and highest (8.1%) among the 540 patients with no ST resolution (P
      <.0001 for trend). In a logistic regression model incorporating other baseline
      predictors of 30-day mortality rate, both a positive myoglobin assay (relative
      risk 1.98, 95% confidence interval 1.00-3.90) and ST resolution <70% (relative
      risk 2.86, 95% confidence interval 1.22-6.69) were independently associated with
      increased mortality rate. At 30 days, mortality rate was 0.4% among patients with
      a negative myoglobin assay and complete ST resolution, 4.8% among patients with
      either a positive myoglobin assay or ST resolution <70%, and 9.6% among those
      with both a positive myoglobin ratio and ST resolution <70% (P <.001 for trend).
      CONCLUSIONS: Within 90 minutes after administering thrombolytic therapy for acute
      myocardial infarction, clinicians can determine the risk for death at the
      patient's bedside with a hand-held myoglobin assay and 2 serial 12-lead
      electrocardiograms. A strategy using these 2 simple, rapid, and inexpensive tests
      may facilitate triage after thrombolytic therapy.

PMID- 10966534
TI  - D-Dimer is an early diagnostic marker of coronary ischemia in patients with chest
      pain.
AB  - BACKGROUND: Chest pain is a frequent symptom in the emergency department and
      often presents a diagnostic challenge. Because coronary thrombosis is a hallmark
      of acute ischemic syndromes, the substrates of the coagulation and fibrinolysis
      cascades may be markers of coronary ischemia. The objective of this study was to
      determine the diagnostic value of several hemostatic markers in patients
      presenting to the emergency department (ED) with chest pain syndromes. METHODS:
      Two hundred fifty-seven consecutive patients with acute chest pain were studied
      in this prospective study conducted in an urban ED. D-Dimer levels were measured
      at admission to the ED in all patients. We also measured thrombin-antithrombin
      complexes, prothrombin fragment 1+2, activated factor VII, and fibrinogen. We
      used regression analysis to estimate the likelihood of myocardial infarction and
      the diagnostic value of D-dimer. RESULTS: D-Dimer and fibrinogen levels were
      significantly higher in patients with acute ischemic events (myocardial
      infarction and unstable angina) than in nonischemic patients (P <.01 and P =.02,
      respectively). The other hemostatic markers were not significantly elevated in
      patients with ischemic events. D-Dimer level >500 microg/L had an independent
      diagnostic value for myocardial infarction and increased the diagnostic
      sensitivity of the electrocardiogram and history from 73% to 92%. CONCLUSION: D
      Dimer, an expression of ongoing thrombus formation and lysis, is a marker of
      substantial incremental value for the early diagnosis of acute coronary syndromes
      presenting with chest pain. It adds independent information to the traditional
      assessment for myocardial infarction. D-Dimer can be incorporated into clinical
      decision models in the ED.

PMID- 10966535
TI  - Negative T waves shortly after ST-elevation acute myocardial infarction are a
      powerful marker for improved survival rate.
AB  - BACKGROUND: Recent studies have reported that negative T waves in the setting of
      acute coronary events are associated with Thrombolysis In Myocardial Infarction
      flow grade 3 in the infarct-related artery and with improved parameters of
      ventricular function rather than with ischemia. METHODS: Patients enrolled in the
      Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries (GUSTO-I) angiographic substudy (ie, patients with acute
      infarction randomly assigned to one of 4 thrombolytic regimens who then underwent
      coronary angiography) were included in this study if they survived at least 24
      hours and had no confounding electrocardiographic factors (n = 1505). RESULTS:
      More patients had negative T waves develop (NT group, n = 938 [62%]) than not (PT
      group, n = 567 [38%]). Peak creatine kinase MB, time to thrombolysis, and
      randomization to accelerated alteplase were no different between the groups.
      Thirty days after admission, 12 patients in the NT group had died versus 25
      patients in the PT group (1.3% vs. 4.4%; P <.001; odds ratio for negative T waves
      0.28; 95% confidence interval 0.14-0.56). The difference persisted when only
      patients who survived at least 3 days were analyzed. After adjusting for relevant
      covariates (including presence of new Q waves in the follow-up
      electrocardiogram), negative T waves were an independent predictor for survival
      (P =. 007; odds ratio for negative T waves 0.38; 95% confidence interval 0. 18
      0.78). Patients in the NT group were 35% more likely to have achieved patency of
      the infarct-related artery, although this difference was not statistically
      significant. CONCLUSIONS: Negative T waves shortly after acute myocardial
      infarction treated with thrombolysis were markers for improved 30-day survival
      rate. This finding merits prospective testing.

PMID- 10966536
TI  - Intravascular ultrasound findings of negative arterial remodeling at sites of
      focal coronary spasm in patients with vasospastic angina.
AB  - BACKGROUND: There are few data about the intravascular ultrasound (IVUS) findings
      in patients with vasospastic angina, especially regarding patterns of vascular
      remodeling. METHODS AND RESULTS: Coronary spasm was documented by angiography and
      electrocardiographic evidence of ischemia in 36 patients after administration of
      ergonovine (cumulative doses up to 350 microg). After relief of spasm with 1000
      microg of intracoronary nitroglycerin, quantitative angiography and IVUS imaging
      were performed and analyzed by standard methods. The 36 focal spasm sites were
      compared with the proximal and distal reference segments. The angiographic
      baseline minimum lumen diameter measured 1.78 +/- 0.66 mm, which decreased to
      0.66 +/- 0.38 mm with ergonovine provocation (P <.0001), increased to 2.66 +/-
      0.64 mm after intracoronary nitroglycerin (P <.0001 compared with baseline and
      after ergonovine), and did not change after IVUS imaging (2.66 +/- 0.63, P =.9).
      By IVUS, atherosclerotic lesions were observed at all coronary spasm sites; the
      mean plaque burden measured 56% at the spasm site and 35% at the reference. Spasm
      site plaque composition was hypoechoic in 31 and hyperechoic, noncalcific in 5;
      there was no calcium. The mean eccentricity index (maximum divided by minimum
      plaque thickness) was 6.7. Positive remodeling (spasm site arterial area greater
      than proximal reference) was present in 5; intermediate remodeling (proximal
      reference greater than spasm site greater than distal reference arterial area)
      was present in 7; and negative remodeling (spasm site arterial area less than
      distal reference) was present in 24. CONCLUSIONS: Sites of vasospasm in patients
      with variant angina showed characteristics of early atherosclerosis, except for
      an unusually high incidence of negative arterial remodeling.

PMID- 10966537
TI  - A Canadian comparison of data sources for coronary artery bypass surgery outcome
      "report cards".
AB  - BACKGROUND: Prior comparisons of administrative versus clinical data for creating
      coronary artery bypass graft (CABG) surgery outcome "report cards" are all from
      the United States and yield inconsistent conclusions regarding the validity of
      administrative data report cards. In this study, we compared 2 CABG surgery
      outcome report cards for Ontario, Canada: one derived from clinical data from the
      Cardiac Care Network of Ontario and one derived from administrative data from the
      Canadian Institute for Health Information. METHODS: Data from 4 fiscal years,
      1992-93 through 1995-96, were used. The Canadian Institute for Health Information
      report card was derived from administrative data only. The Cardiac Care Network
      report card drew on prospectively collected clinical information that included
      variables such as left ventricular ejection fraction but also required linkages
      to the Canadian Institute for Health Information data for ascertainment of
      selected comorbidities and in-hospital mortality rates. Logistic regression
      models were used to calculate risk-adjusted death rates for each of the 9
      hospitals performing CABG surgery in Ontario. RESULTS: The risk-adjusted death
      rates were quite similar between data sources for 7 of the 9 hospitals. For 2
      hospitals, rather large absolute differences in adjusted death rates of 0.58% and
      0.64% were seen between report cards. There was a strong correlation between data
      sources for risk-adjusted hospital death rates (intraclass correlation
      coefficient = 0.927, P <.001) and for rankings of adjusted hospital death rates
      (Spearman correlation coefficient = 0.828, P =.02). CONCLUSION: These results
      from Ontario, Canada, reveal general similarities between administrative and
      clinical data report cards for CABG surgery. However, clinical data are likely
      needed if individual hospitals are to be publicly scrutinized in outcome report
      cards.

PMID- 10966538
TI  - Association of patients' perception of health status and exercise
      electrocardiogram, myocardial perfusion imaging, and ventricular function
      measures.
AB  - BACKGROUND: Patients' viewpoint of their health status is increasingly used as an
      important outcome measure of the success of treatments. Because clinicians rarely
      formally measure patients' health-related quality of life, the question arises
      whether noninvasive testing for ischemia can provide similar information
      regarding physical functioning and general health perception. METHODS: We
      measured physical functioning and general health status with the Medical Outcomes
      Study Short Form (SF-36) survey in 195 consecutive patients (68% male, mean age
      55.6 +/- 11.1 years) referred for exercise testing with myocardial perfusion
      imaging. The survey was completed immediately before the exercise test. RESULTS:
      In the multivariate analysis, the strongest predictor of physical functioning and
      general health perception was metabolic equivalents. However, the best model,
      including demographic, clinical, and test variables, predicted only 14% of the
      variation in physical functioning and 10% of the variability in general health
      perception. CONCLUSIONS: The variation in physical functioning and general health
      perception, as measured by the SF-36, among patients referred for exercise
      testing is not predicted well by the results of the test. As expected, several
      test results are significantly associated with physical functioning and general
      health perception; however, there was substantial overlap among individual
      patients, suggesting that the parameters are poor surrogates for the actual
      assessment of the domains. If these domains are deemed important to tracking
      patient outcomes, then they should supplement the current assessments of these
      patients.

PMID- 10966539
TI  - Expensive medical technologies and "indication extrapolation": the case of
      implantable cardioverter-defibrillators.

PMID- 10966540
TI  - Coagulation indicators in patients with paroxysmal atrial fibrillation: effects
      of electric and pharmacologic cardioversion.
AB  - The aim of this study was to determine whether paroxysmal atrial fibrillation
      (PAF) and/or restoration to sinus rhythm with electric or pharmacologic
      cardioversion induce modifications to the coagulation system. Thirty-five
      patients with PAF undergoing either electric (n = 11) or pharmacologic (n = 24)
      cardioversion were studied. Fibrinopeptide A and D-dimer blood samples were taken
      immediately before and after cardioversion at different intervals. When compared
      with the control group (n = 70), the precardioversion fibrinopeptide A plasma
      values were significantly elevated (11.8 vs 2.5 ng/mL). Fibrinopeptide A plasma
      values were significantly reduced 5 minutes after cardioversion (11.8 vs 5.3
      ng/mL) and remained stable throughout the follow-up sequential measurements. D
      dimer plasma values were significantly increased (measured at 12 hours and at day
      7) in patients who underwent electrical cardioversions only. A positive
      correlation (R(2) = 0.76) was found between the energy delivered for
      cardioversion to sinus rhythm and D-dimer plasma values on day 7. In patients
      with PAF, levels of fibrinopeptide A, an indicator of coagulation activation, are
      elevated and soon reduced by the restoration of sinus rhythm. Electric, but not
      pharmacologic, cardioversion induces an early activation of the fibrinolytic
      system.

PMID- 10966541
TI  - Sex-dependent electrocardiographic pattern of cardiac repolarization.
AB  - BACKGROUND: Although sex-dependent differences in cardiac repolarization have
      been known for many years, few attempts have been carried out to define the
      individual contribution of each electrocardiographic (ECG) repolarization
      variable to the sex-dependent pattern. METHOD AND RESULTS: We analyzed several
      ECG repolarization variables that reflect both the duration and the rate of
      repolarization in 500 normal healthy subjects between the ages of 20 and 80 years
      (250 men and 250 women) and distributed into 5 groups according to age. Cardiac
      repolarization, measured in the precordial lead exhibiting the highest T-wave
      amplitude, was found to be shorter and faster in normal men compared with normal
      women (P <.001). The parameters with the highest individual weight in determining
      these sex differences were the J point and the ST angle, as indicated by
      nonlinear (logistic) multivariate regression analysis. CONCLUSION: We conclude
      that changes in the duration and rate of early repolarization are determinants
      for these sex-dependent ECG pattern differences.

PMID- 10966542
TI  - Decreasing the number of leads required for an implantable atrial defibrillator:
      use of a new 2-lead system.
AB  - BACKGROUND: The purpose of this study was to evaluate the use of a new 2-lead
      system for detection of atrial fibrillation (AF) and atrial defibrillation.
      METHODS: In 16 patients undergoing elective cardioversion of AF, a 2-lead system
      was compared with the conventional 3-lead system in a randomized trial. The new 2
      lead system consisted of a catheter with a distal bipolar right ventricular
      electrode pair and a proximal right atrial shock electrode coil and a separate
      decapolar defibrillation catheter in the coronary sinus. For the 3-lead system,
      an additional decapolar catheter was placed in the right atrium. AF and sinus
      rhythm signal amplitude detection and atrial defibrillation threshold (ADFT) were
      compared in each patient with both systems. RESULTS: Successful defibrillation
      was obtained in all patients. ADFT for the 2-lead system was significantly higher
      compared with the 3-lead system (370 +/- 112 vs 316 +/- 100 V, P < .05; 9.3 +/-
      5.2 vs 6.8 +/- 4.2 J, P < .05). In contrast, there was an increase in impedance
      for the 3-lead system (77 +/- 16 ohms vs 68 +/- 13 ohms; P < .05). AF had a lower
      signal amplitude compared with sinus rhythm for both systems (P < .05), and the 2
      lead system had a lower signal amplitude compared with the 3-lead system for both
      rhythms (P < .05). CONCLUSION: The use of a 2-lead system with this configuration
      is not superior to the 3-lead system regarding AF signal amplitude detection and
      ADFT. Further study is needed with implantable-quality leads in place of the
      temporary catheters used in this study.

PMID- 10966543
TI  - Effects of diltiazem pretreatment on direct-current cardioversion in patients
      with persistent atrial fibrillation: a single-blind, randomized, controlled
      study.
AB  - BACKGROUND: Electric conversion of atrial fibrillation is the most widely used
      and effective treatment for sinus rhythm restoration. However, it has a limited
      success rate and a high recurrence rate. HYPOTHESIS: Pretreatment with calcium
      channel blocker may improve the efficacy by reversing the so-called "electric
      remodeling" phenomenon, also related to overload in cytosolic calcium. METHODS:
      The efficacy of diltiazem or amiodarone pretreatment (oral, 1 month before and 1
      month after conversion) on direct-current conversion of persistent atrial
      fibrillation was assessed in 120 patients, randomly assigned to 3 matched groups:
      A (n = 44, diltiazem); B (n = 46, amiodarone), and C (n = 30, digoxin). RESULTS:
      Before electric conversion, all treatments significantly decreased mean heart
      rate. Spontaneous conversion to sinus rhythm was achieved in 6% of patients of
      group A (3 of 46) versus 25% of group B (11 of 44) and 3% (1 of 30) of group C
      (A/C vs B, P < .005). Current conversion was more successful in group B (91%)
      compared with group A (76%) and group C (67%) (B vs A/C, P < .05), with no
      difference in the electric threshold for effective conversion (P = not
      significant). At the 24-hour time point, early relapse of atrial fibrillation was
      similar between groups A and B (A, 2%; B, 3%; P = not significant) and lower than
      group C (12%) (P < .01), whereas at the 1-month time point the recurrence rate
      was lower in group B (28%) versus groups A (56%) and C (78%) (B vs A/C, P < .01).
      No significant side effects were reported. CONCLUSIONS: Although diltiazem seems
      to be as effective as amiodarone in reducing early atrial fibrillation
      recurrences, diltiazem is less effective in determining spontaneous or electric
      conversion, with a higher recurrence rate at 2 months. Diltiazem pretreatment
      could be considered as only a second choice treatment in those patients in whom
      amiodarone is contraindicated.

PMID- 10966544
TI  - Pilsicainide for conversion and maintenance of sinus rhythm in chronic atrial
      fibrillation: a placebo-controlled, multicenter study.
AB  - BACKGROUND: Pilsicainide is a newly synthesized antiarrhythmic agent with class
      Ic properties. Various antiarrhythmic agents have been used to convert atrial
      fibrillation (AF) to sinus rhythm or decrease the rate of relapse of AF. METHODS:
      We randomly assigned 62 patients with chronic AF to oral treatment of either a
      placebo (10 patients) or 150 mg/day of pilsicainide (52 patients) for 4 weeks
      before electrical cardioversion. Before oral administration of pilsicainide, 41
      patients underwent transesophageal echocardiography to investigate whether there
      was thrombus formation in the heart chambers. Patients without pharmacologic
      defibrillation underwent direct current cardioversion to restore sinus rhythm.
      After successful cardioversion, all patients continued to receive pilsicainide
      and were monitored for up to 2 years. RESULTS: Before cardioversion, 11 patients
      in the pilsicainide group (21%) reverted to sinus rhythm. No patients in the
      placebo group reverted to sinus rhythm. Direct current cardioversion was
      performed in 51 patients; however, 8 patients were not converted to sinus rhythm
      (5 patients receiving pilsicainide, 3 patients receiving placebo), and 3 patients
      needed intracardiac cardioversion to convert to sinus rhythm. Asymptomatic
      bradyarrhythmias were observed in 5 patients in the pilsicainide group. During
      the follow-up period, 33 patients (71%) in the pilsicainide group remained in
      sinus rhythm at 1 month; this number decreased to 23 patients (49%) at 3 months,
      20 (43%) at 6 months, 16 (34%) at 12 months, 16 (34%) at 18 months, and 16 (34%)
      at 24 months. All patients receiving placebo continued to receive placebo after
      the cardioversion, and AF recurred a few days after cardioversion in all cases.
      No independent discriminant variables were identified in the groups between
      maintenance and nonmaintenance of sinus rhythm. Although no serious side effects
      regarding pilsicainide have been documented, one patient died of acute myocardial
      infarction, most likely not related to pilsicainide administration. CONCLUSIONS:
      Pilsicainide is effective in restoring or maintaining sinus rhythm in patients
      with chronic AF lasting longer than an average duration of 22 months. No major
      adverse effects were observed.

PMID- 10966545
TI  - Increased risk of congestive heart failure among infarctions with nighttime
      onset.
AB  - BACKGROUND: The onset of acute myocardial infarction varies by time of day, with
      a peak in the morning and a trough at night. Whether infarct-related
      complications differ by the timing of the infarction is unknown. METHODS AND
      RESULTS: In the Determinants of Myocardial Infarction Onset Study, we performed
      chart reviews and face-to-face interviews with 3625 patients with acute
      myocardial infarction. We assessed the time of onset of symptoms, the presence of
      ventricular tachycardia or congestive heart failure, and peak creatine kinase
      levels (in 1043 patients). We found significant circadian variation in the risk
      of congestive heart failure (P =.001). The risk dropped from 17% for infarctions
      that began between 6 PM and midnight to 10% for infarctions that began between 6
      AM and noon. Adjustment for differences in the time from symptom onset to
      presentation for care and use of thrombolytic agents did not change the results.
      We found no circadian variation in the risk of ventricular tachycardia or in peak
      creatine kinase levels. CONCLUSIONS: The risk of congestive heart failure is
      highest among infarctions that begin at night. Further research may clarify
      whether this reflects differences in the pathophysiologic characteristics of
      infarction or the quality of medical care provided for daytime and nighttime
      infarctions.

PMID- 10966546
TI  - Heart transplant center practice patterns affect access to donors and survival of
      patients classified as status 1 by the United Network of Organ Sharing.
AB  - OBJECTIVE: To determine the effect of adult cardiac transplant center practice
      patterns within a single organ procurement organization on access to donors and
      survival for patients listed as United Network of Organ Sharing (UNOS) status 1.
      METHODS: A total of 662 patients listed (January 1, 1992, through December 31,
      1995) as UNOS status 1 for heart transplantation by the 4 adult cardiac
      transplant centers in an organ procurement organization were analyzed in a
      retrospective cohort study to determine differences in clinical outcomes.
      RESULTS: The specific center at which an individual was listed as UNOS status 1
      was a significant independent predictor of receiving a transplant (odds ratios
      for 3 centers vs center with highest likelihood = 0.73, 0.64, 0.35, respectively;
      P <. 01). Only 1 center had a significantly increased mortality rate compared
      with the other centers (odds ratio 2.03, P <.01). CONCLUSION: Within a single
      regional organ procurement organization, cardiac transplant centers demonstrate
      significant variability in the likelihood of transplantation and survival for
      patients listed as UNOS status 1.

PMID- 10966547
TI  - Flash pulmonary edema: association with hypertension and reoccurrence despite
      coronary revascularization.
AB  - BACKGROUND: The sudden development of acute (flash) pulmonary edema may be an
      indication for coronary angiography and revascularization. However, the
      prevalence of coronary artery disease in these patients and the outcome after
      revascularization are not known. METHODS AND RESULTS: We evaluated 46 patients
      with an initial presentation of flash pulmonary edema requiring hospitalization
      and obtained up to 3 years of follow-up in 45 patients. There were 22 men and 24
      women, 44 to 84 years of age (67 +/- 10 years, mean +/- SD). Systolic blood
      pressure on admission was 194 +/- 38 mm Hg. Twenty-four patients required
      intubation and mechanical ventilation. Left ventricular ejection fraction was
      >40% in 27 of 46 patients. Thirty-eight patients underwent coronary angiography;
      33 had obstructive coronary artery disease. One other patient had regional wall
      motion abnormalities. Nineteen patients underwent coronary revascularization
      surgically and 8 percutaneously. Overall, flash pulmonary edema reoccurred in one
      half of the patients. Of the 19 patients who underwent coronary
      revascularization, by 6 months there was 1 death and 9 patients had been
      hospitalized with recurrent pulmonary edema. CONCLUSIONS: Many patients with
      flash pulmonary edema have preserved systolic left ventricular function and
      coronary artery disease. Flash pulmonary edema frequently reoccurs in association
      with marked systolic hypertension, even after coronary revascularization. This
      suggests that control of hypertension is important and that coronary
      revascularization may not be adequate to prevent reoccurrence of flash pulmonary
      edema.

PMID- 10966548
TI  - Enhanced prognostic stratification of patients with left ventricular hypertrophy
      with the use of single-photon emission computed tomography.
AB  - BACKGROUND: Patients with left ventricular hypertrophy (LVH) are at increased
      risk of future cardiovascular events. Little is known about risk stratification
      of these patients with the use of myocardial perfusion imaging. This study sought
      to assess the prognostic stratification of patients with LVH by using myocardial
      perfusion single-photon emission computed tomography (SPECT). METHODS AND
      RESULTS: We studied 633 consecutive patients with electrocardiographic evidence
      of LVH who underwent dual isotope myocardial perfusion SPECT (rest thallium
      201/stress technetium 99m sestamibi) and were followed up for a mean period of 22
      +/- 7 months. During the follow-up period, 67 events (35 cardiac deaths and 32
      nonfatal myocardial infarctions) occurred (6% annual event rate). The results of
      the perfusion scan significantly risk-stratified the population; patients with
      normal scans had a low rate of nonfatal myocardial infarction and cardiac death
      (<1% per year of follow-up). The rates of cardiac events increased significantly
      as a function of the scan result: 4.9% in patients with mildly abnormal scans and
      10. 3% in moderately to severely abnormal scans. Cox proportional hazards
      analysis demonstrated that after adjusting for pretest likelihood of coronary
      artery disease (the most predictive clinical variable; chi(2) = 15.5, P <.001),
      summed stress score (the most predictive nuclear variable; chi(2) = 18, P <.0001)
      added significant incremental prognostic information (global chi(2) increased
      from 15.5 to 36; P <.001). CONCLUSIONS: In patients with LVH with an overall high
      cardiac event rate, SPECT provided enhanced stratification by adding significant
      incremental prognostic information over clinical and historic variables.

PMID- 10966549
TI  - Cyclic variation of integrated ultrasound backscatter in the left ventricle
      during the early neonatal period.
AB  - BACKGROUND: Significant changes in the contractility and histologic structure of
      the ventricular myocardium occur during the early neonatal period. Cyclic
      variation (CV) of ultrasonic integrated backscatter (IBS) reflects myocardial
      contractile performance. The aim of this study was to define normal values of and
      its serial changes in CV of IBS in the left ventricle of normal neonates. METHODS
      AND RESULTS: We recorded long-axis IBS images in 169 healthy neonates within 14
      days after birth (mean 4.6 +/- 4.2 days) and in 84 infants and children (mean age
      8.7 +/- 5.2 years). For each, we obtained CV of IBS in the interventricular
      septum (CV(IVS)) and the posterior wall (CV(PW)). In neonates, there was a
      significant linear correlation between CV and date after birth in measurements of
      both the interventricular septum and the posterior wall (r = 0.57 and 0. 60,
      respectively). In infants and children, there was no significant relation between
      age and CV(IVS) or CV(PW). In neonates >4 days after birth, the magnitude of
      CV(IVS) was not significantly different from that in infants or children. By
      contrast, the magnitude of CV(PW) was still significantly decreased in neonates
      >9 days after birth compared with that in infants and children (P <. 005). The
      ratio of CV(IVS) to CV(PW) (CV(IVS)/CV(PW)) was significantly higher in neonates
      than in infants and children (0.99 +/- 0.29 vs 0.80 +/- 0.22, P <.001).
      CONCLUSIONS: Both CV(IVS) and CV(PW) in neonates gradually increase after birth,
      indicating developmental maturation of the left ventricle. High values of
      CV(IVS)/CV(PW) might reflect the remnant of relatively high contractile
      performance in the right ventricle during fetal life.

PMID- 10966550
TI  - Accuracy of three-dimensional echocardiography with unrestricted selection of
      imaging planes for measurement of left ventricular volumes and ejection fraction.
AB  - BACKGROUND: Accurate, reproducible, noninvasive determination of left ventricular
      (LV) volumes and ejection fraction (EF) is important for clinical assessment,
      risk stratification, selection of therapy, and serial monitoring of patients with
      cardiovascular disease. Three-dimensional echocardiography (3DE) approaches have
      demonstrated significantly greater accuracy than current clinical 2DE, but the
      clinical utility of 3DE has been limited because of the need for substantial
      modifications to scanning technique (eg, all image acquisition from a single
      acoustic window) or cumbersome additional hardware. We describe a novel 3DE
      system without these limitations and its application to patients. METHODS AND
      RESULTS: Twenty-five patients were examined by 3DE, 2DE, and magnetic resonance
      imaging (MRI). The 3DE system used a magnetic scanhead tracking device, and
      volumes were computed with a novel deformable shell model. End-diastolic volumes
      and EF by MRI ranged from 96 to 375 mL and 18% to 73%, respectively. There was
      excellent correlation, without statistically significant differences, between MRI
      and 3DE for end-systolic volume (ESV) (r(2) = 0.99) and end-diastolic volume
      (EDV) (r(2) = 0.98), ventricular stroke volume (SV) (r(2) = 0.93), and EF (r(2) =
      0.97), with standard error estimates less than 10 mL for volumes and 3% for EF.
      Conventional 2DE consistently underestimated volumes (EDV, P <.01; ESV, P <.01;
      SV, P <.05); correlations with MRI were r(2) = 0.91 for ESV, r(2) = 0.88 for EDV,
      r(2) = 0.62 for SV, and r(2) = 0.72 for EF. Standard error estimates ranged from
      16 to 20 mL for ventricular volumes and 9% for EF. Interobserver variability was
      reduced 3-fold with use of 3DE. CONCLUSIONS: The novel 3DE system allows
      unrestricted selection and combination of acoustic windows in a single
      examination, improves accuracy of estimates of LV volumes and EF 3-fold compared
      with 2DE, and is practical for routine clinical assessment of LV size and
      function in patients with a wide range of cardiac pathology.

PMID- 10966551
TI  - Echocardiographic markers for mitral valve surgery to preserve left ventricular
      performance in mitral regurgitation.
AB  - BACKGROUND: The timing of mitral valve (MV) surgery to preserve left ventricular
      (LV) contractility in patients with mitral regurgitation (MR) has been defined by
      complex cardiac catheterization techniques. Whether noninvasive methods can
      identify patients with MR, a normal LV ejection fraction, and early LV
      contractile impairment is unknown. We hypothesized that echocardiographic
      measures would separate patients with MR and a normal LV ejection fraction into
      those with and without contractile dysfunction and, thus, prospectively predict
      the response of LV size and performance to MV surgery. METHODS AND RESULTS: We
      studied 27 patients with micromanometer LV pressures and radionuclide angiography
      to obtain a determination of LV volumes and ejection fraction and calculate
      chamber elastance, a measure of LV contractility, before MV surgery.
      Echocardiographic studies were performed before MV surgery and repeated at 3 and
      12 months after surgery. Age, New York Heart Association class, LV plus maximum
      pressure per unit change in time, LV systolic and end-diastolic pressures, and
      echocardiographic posterior wall thickness and radius to wall thickness ratio did
      not identify preoperative LV contractile dysfunction. However, other
      echocardiographic measures were related to LV contractility, including LV end
      diastolic dimension (r = -0.50, P <.005), LV end-systolic dimension (r = -0.60, P
      <.0001), and LV fractional shortening (r = 0.50, P =.005). From analysis of
      receiver operator characteristic curves, an LV end-systolic dimension of >/=40 mm
      was identified as most predictive for separating patients with MR before surgery
      into those with and without LV contractile dysfunction (sensitivity of 82% and
      specificity of 100%). The patients with MR and impaired preoperative LV
      contractility showed a dramatic deterioration in LV fractional shortening at 3
      months after MV surgery (P =.01), which recovered to within the normal range for
      fractional shortening at 12 months (P =.02) from a progressive reduction in LV
      end-systolic dimension. This response in LV size and performance temporally
      differed from that in the patients with MR and normal contractility (2-way
      analysis of variance P <.0001). However, at 12 months after MV surgery, LV end
      diastolic dimension, end-systolic dimension, and fractional shortening were
      normal in both groups of patients with MR. CONCLUSION: We conclude that
      echocardiographic measures, particularly an end-systolic dimension of >/=40 mm,
      may be useful for identifying patients with MR before surgery with early, occult
      LV contractile dysfunction in whom MV surgery may be recommended to preserve LV
      systolic performance.

PMID- 10966552
TI  - Clopidogrel for prevention of major cardiac events after coronary stent
      implantation: 30-day and 6-month results in patients with smaller stents.
AB  - OBJECTIVES: We developed this study to assess the procedural outcome,
      complications, and clinical follow-up in patients treated with different
      antiplatelet regimens after intracoronary stent implantation with small stents.
      Three hundred sixty-one consecutive patients, in whom at least one 3.0-mm
      intracoronary stent was implanted, were studied. METHODS: The study was a
      prospective, observational registry of unselected consecutive patients treated in
      our institution. Patients who underwent stent implantation between December 1997
      and July 1998 were treated with aspirin and ticlopidine; those who received
      stents between August 1998 and February 1999 were treated with aspirin and
      clopidogrel. RESULTS: In the group treated with ticlopidine, there were 190
      patients who had 253 lesions treated with 274 stents. Mean age was 59.1 years,
      72% were male, 31% had unstable angina, 64% had 1 stent, 36% had >1 stent, and
      23% had multivessel intervention. In the group treated with clopidogrel, there
      were 171 patients who had 226 lesions treated with 245 stents. Mean age was 60.4
      years, 79% were male, 26% had unstable angina, 70% had 1 stent, 30% had >1 stent,
      and 26% had multivessel intervention. Complications at 30 days in the ticlopidine
      group were death in 1 (0.5%), stent occlusion in 3 (1. 6%; all reopened with
      repeat angioplasty), non-Q-wave myocardial infarction in 2 (1%), and urgent
      revascularization in 4 (2%). Complications at 30 days in the clopidogrel group
      were noncardiac death in 1 (1.2%), cardiac death in 1 (1.2%), stent occlusion in
      0, non-Q-wave myocardial infarction in 3 (1.8%), and urgent revascularization in
      0. Follow-up was available in 100% of patients in both groups (mean 253 +/- 75
      days in the ticlopidine group, 198 +/- 53 days in the clopidogrel group).
      Complications at >30 days in the ticlopidine group were death in 1 and clinical
      restenosis in 11 (5.8%); 1 additional patient had an admission with unstable
      angina to the local hospital. Hence, recurrent angina as a consequence of target
      lesion restenosis occurred in 5.8%. Complications at >30 days in the clopidogrel
      group were death in 0 and clinical restenosis in 8 (4.7%); 2 additional patients
      were admitted with unstable angina to the local hospital, and 1 patient had a
      myocardial infarction 164 days after stent implantation. Hence, recurrent angina
      as a consequence of target lesion restenosis occurred in 4.7%. There were no
      significant differences in complications between the 2 groups. CONCLUSIONS: Our
      observations suggest that clopidogrel can be used instead of ticlopidine in
      patients treated with stents with a diameter of </=3.0 mm, without any increase
      in major adverse cardiac events, both within the first 30 days and at medium-term
      follow-up. Clopidogrel has significant cost advantages over ticlopidine, and
      carries a superior side-effect profile. We suggest that, in combination with
      aspirin, clopidogrel should replace ticlopidine as standard antiplatelet therapy
      after intracoronary stent implantation.

PMID- 10966554
TI  - Safety of intracoronary Doppler flow measurement.
AB  - BACKGROUND: With the introduction of Doppler-tipped guide wires, intracoronary
      Doppler flow measurement has been increasingly accepted as an additional
      diagnostic approach in the catheterization laboratory. However, the safety of
      intracoronary Doppler flow measurement has not been well-investigated. The
      purpose of our study was to evaluate the safety of intracoronary Doppler flow
      measurement using the Doppler FloWire (Cardiometrics, Mountain View, Calif).
      METHODS AND RESULTS: A total of 906 patients were examined by intracoronary
      Doppler with a 0.014-inch or an 0.018-inch Doppler FloWire. For coronary flow
      reserve measurement, intracoronary injection of adenosine or papaverine was used.
      Of the patients studied, 77 were cardiac transplant recipients and 829 were
      patients who had not received a transplant, of whom 617 had undergone diagnostic
      coronary procedures and 212 had coronary interventions. In 27 (2.98%) of 906
      patients adverse cardiac events were observed. Fifteen (1.66%) of 906 patients
      had severe transient bradycardia develop (asystole or second- to third-degree
      atrioventricular block) after intracoronary administration of adenosine, 14 of
      which occurred in the right coronary artery and 1 in the left anterior descending
      artery. Nine (0.99%) of 906 patients had coronary spasm during the passage of the
      Doppler wire (5 in the right coronary artery, 4 in the left anterior descending
      artery). Two (0.22%) of 906 patients had ventricular fibrillation during the
      procedure. Hypotension with bradycardia and ventricular extrasystole each
      occurred in 1 (0.11%) of 906 patients. The incidence of complication was
      significantly higher in transplant recipients than in patients who underwent
      either diagnostic or interventional procedures (12.99% vs 2.43% vs 0.94%, P
      <.001). The Doppler measurements in the right coronary artery were associated
      with a higher incidence of complications, especially bradycardia, compared with
      the left anterior descending and the left circumflex arteries (right coronary,
      5.87% vs left anterior descending, 1.05% vs left circumflex, 0.17%; P <.001). All
      complications were cured medically. CONCLUSION: Intracoronary Doppler flow
      measurement with Doppler wires and intracoronary administration of adenosine is a
      safe method. However, severe complications such as bradycardia and coronary spasm
      can occur. Attention should be paid to the examination of the right coronary
      artery, especially in heart transplant recipients.

PMID- 10966553
TI  - Abciximab, ticlopidine, and concomitant abciximab-ticlopidine therapy: ex vivo
      platelet aggregation inhibition profiles in patients undergoing percutaneous
      coronary interventions.
AB  - BACKGROUND: We examined the ex vivo platelet aggregation profiles of patients who
      underwent percutaneous coronary intervention and received either abciximab,
      ticlopidine, or both agents. STUDY DESIGN AND METHODS: The trial was a
      prospective, nonrandomized, single-center, open-label study of 42 patients
      undergoing percutaneous coronary intervention who received the following
      regimens: group 1, abciximab (0.25 mg/kg bolus and 12-hour, 0.125 microg/kg per
      minute infusion); group 2, ticlopidine (250 mg twice daily for 14 consecutive
      days, initiated 12 to 18 hours before intervention); group 3, abciximab plus
      ticlopidine initiated 12 to 18 hours before procedure; and group 4, abciximab
      plus ticlopidine initiated 72 to 96 hours before procedure. Platelet aggregation
      measurements to adenosine diphosphate (ADP) and a thrombin receptor activating
      peptide (TRAP, 8 micromol/L) were obtained before ticlopidine treatment, after
      initiation of ticlopidine, and immediately before abciximab treatment and
      intervention, then at several time periods after onset of abciximab treatment.
      Platelet surface abciximab levels were monitored by flow cytometry. RESULTS:
      Neither ticlopidine regimen resulted in appreciable platelet inhibition before
      intervention and before administration of abciximab. In the ticlopidine-only arm,
      suppression of platelet aggregation to the weakest stimuli (5 micromol/L ADP; 23%
      +/- 7.5%) was detected within 24 hours after intervention, with maximal
      inhibition to both 5 and 20 micromol/L ADP observed 7 days after intervention
      (48% +/- 7.9% and 18% +/- 8.7%, respectively). In contrast, ticlopidine
      marginally suppressed TRAP-mediated platelet activation at times when maximal
      effects on ADP-mediated platelet aggregation were evident. Neither ticlopidine
      regimen appreciably enhanced platelet inhibition during or shortly after
      cessation of abciximab treatment. For all 3 abciximab treatment arms, profound
      inhibition of ADP-induced (>80%) and TRAP-induced (>65%) platelet aggregation was
      observed 2 hours after treatment. In the abciximab-only arm, platelet aggregation
      responses gradually recovered, with the rate of response directly proportional to
      the strength of stimuli. However, in the ticlopidine plus abciximab arms,
      recovery of platelet aggregation at later times (7 and 14 days) reached a plateau
      and reflected the extent of inhibition observed in ticlopidine-treated patients.
      No difference in the clearance of surface-bound abciximab from circulating
      platelets was observed between the abciximab and abciximab plus ticlopidine arms.
      CONCLUSIONS: Concomitant abciximab plus ticlopidine treatment yields a platelet
      inhibition profile that is a composite of the effects of the 2 agents. In the
      early stages of treatment, inhibition of ex vivo platelet aggregation was
      mediated primarily by abciximab; effects were more moderate and were
      predominately mediated by ticlopidine.

PMID- 10966555
TI  - Comparison of artificial neural networks with logistic regression in prediction
      of in-hospital death after percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: Our objective was to compare artificial neural networks (ANNs) with
      logistic regression for prediction of in-hospital death after percutaneous
      transluminal coronary angioplasty and to assess the impact of guiding initial ANN
      variable selection with univariate analysis. BACKGROUND: ANNs can detect complex
      patterns within data. Criticisms include the unpredictability of variable
      selection. They have not previously been applied to outcomes modeling for
      percutaneous coronary interventions. METHODS: A database of consecutive (n =
      3019) percutaneous transluminal coronary angioplasty procedures from an academic
      tertiary referral center between July 1994 and July 1997 was used. An ANN was
      developed for 38 variables (unguided model) (n = 1554). A second model was
      developed with predictors from an univariate analysis (guided model). Both were
      compared with a logistic regression model developed from the same database. Model
      validation was performed on independent data (n = 1465). Model predictive
      accuracy was assessed by the area under receiver operating characteristic curves.
      Goodness of fit was assessed with the Hosmer-Lemeshow statistic. RESULTS: Sixty
      unguided and guided ANNs were developed. Predictive accuracy and model
      calibration for all models were similar for training data but were significantly
      better for logistic regression for independent validation data. Overestimation of
      event rate in higher risk patients accounted for the majority of discrepancy in
      model calibration for the ANNs. This difference was partially amended by guiding
      variable selection. CONCLUSION: ANNs were able to model in-hospital death after
      percutaneous transluminal coronary angioplasty when guiding variable selection.
      However, performance was not better than traditional modeling techniques. Further
      investigations are needed to understand the impact of this methodology on
      outcomes analysis.

PMID- 10966556
TI  - Flow-mediated vasoactivity and circulating adhesion molecules in
      hypertriglyceridemia: association with small, dense LDL cholesterol particles.
AB  - BACKGROUND: Endothelial dysfunction is considered one of the earliest events in
      the process of atherosclerosis, and an impaired vasodilatory response has been
      reported in patients with dyslipidemias. However, the independent association
      between hypertriglyceridemia and endothelial dysfunction is controversial, and
      the relation between endothelium-dependent vasodilation and circulating cell
      adhesion molecules as markers of endothelial dysfunction has not been fully
      determined. METHODS: Brachial artery flow mediated vasodilation (FMV) and the
      soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular
      adhesion molecule-1 (sICAM-1) were determined after overnight fasting in 16 men
      with hypertriglyceridemia (age 33 +/- 6 years) and in 16 age-matched healthy men
      with normal triglycerides and cholesterol. Subjects who smoked and those with
      known cardiovascular disease, diabetes, hypertension, recent or active
      infections, or any other disease that could affect leukocyte activation were
      excluded from the study. RESULTS: Compared with normal subjects, subjects with
      hypertriglyceridemia showed a higher level of sVCAM-1 and sICAM-1 (both P <.001),
      a reduced FMV (P <.01), and a smaller LDL particle size (P <.05). FMV had a
      significant inverse correlation with sVCAM-1 (r = -0.61, P <.001) and sICAM-1 (r
      = -0.38, P <.03). LDL particle size had a strong, direct association with FMV (r
      = 0.75, P <.001) and an inverse association with adhesion molecules. By multiple
      regression analysis, triglycerides (P <.001) and small LDL particle size (P
      <.002) predicted a reduced FMV. CONCLUSIONS: Serum level of cell adhesion
      molecules is increased and FMV is impaired in young healthy men with
      hypertriglyceridemia compared with age-matched men with normal lipid levels.
      Small, dense LDL particles may play a role in determining endothelial dysfunction
      in these subjects.

PMID- 10966557
TI  - Low caloric expenditure in cardiac rehabilitation.
AB  - BACKGROUND: Total physical activity energy expenditure is a determinant of weight
      loss and risk factor modification in adults. There has been very little study of
      physical activity energy expenditure in cardiac rehabilitation populations.
      METHODS: Exercise-related energy expenditure was calculated in 112 patients with
      coronary artery disease in an outpatient cardiac rehabilitation program. Gross
      energy expenditure was estimated with the heart rate/oxygen consumption relation
      as measured during metabolic exercise testing with expired gas analysis. RESULTS:
      The average exercise training energy expenditure (ETEE) per cardiac
      rehabilitation exercise session was quite low at 270 +/- 112 kcal. Baseline
      fitness level (peak oxygen consumption), body weight, total exercise duration per
      session, age, and body mass index were all significant determinants of ETEE (r =
      0.56 to -0.37, all P <.01). Additionally, patients who had undergone coronary
      bypass surgery and patients with medical comorbidities expended significantly
      fewer calories during exercise. In women, there was a relation between ETEE and
      change in total and LDL cholesterol (r = -0.43 and -0.45, respectively), although
      no such relation was observed in men. CONCLUSION: Cardiac rehabilitation exercise
      training, as currently structured, burns surprisingly few calories and has little
      impact in the short term (3 months) on measures of obesity and lipid risk
      factors. Alternative training programs should be considered to maximize caloric
      expenditure and modify specific risk factors such as obesity and dyslipidemia.

PMID- 10966558
TI  - Transcatheter closure of fenestrations and excluded hepatic veins after fontan:
      versatility of the Amplatzer device.
AB  - BACKGROUND: The aim of this study was to evaluate the Amplatzer septal occluder
      (ASO) for transcatheter closure of fenestrations and excluded hepatic veins in
      patients after modified Fontan operations. Residual right-to-left shunts have
      improved surgical results of the Fontan operation. Shunt closure may eventually
      be desirable to eliminate hypoxemia and reduce risk of embolic complications.
      METHODS AND RESULTS: Ten patients with hypoxemia caused by residual shunts after
      Fontan procedures were evaluated for closure. After favorable results of test
      occlusion, all shunts were closed with the use of the ASO. Eight ASOs were used
      to close fenestrations in 7 patients with 6F transvenous sheaths. Three ASOs were
      used to close excluded hepatic veins in 3 patients with 6F venous sheaths and
      transbaffle punctures. Fluoroscopy and transesophageal echocardiography were used
      to guide device placement. Device placement in all patients was successful. All
      shunts were closed by angiography after device placement. While breathing room
      air, systemic oxygen saturation rose from 87.9% +/- 3.0% to 96.3% +/- 0. 9% (P
      <.001) in the patients. There were no complications of the implant procedures and
      none noted in outpatient follow-up. CONCLUSIONS: This experience suggests that
      the ASO is safe and effective for closing surgical shunts after Fontan
      procedures. The ASO design allows closure of excluded hepatic veins and has
      advantages over other devices in closure of fenestrations.

PMID- 10966560
TI  - Atypical glandular cells of undetermined significance: clinically significant
      lesions and means of patient follow-up.
AB  - BACKGROUND: The clinical significance of atypical glandular cells of undetermined
      significance (AGUS) remains poorly understood, and patient management is not
      standardized. The authors evaluated the rate, qualification, and follow-up (FU)
      findings of AGUS patients. METHODS: Computerized records from the authors'
      institution were searched from April 1992 to December 1997 for diagnoses of AGUS.
      Results of cytologic and histologic FU were evaluated up to 48 months of FU.
      Clinically significant lesions were defined as squamous intraepithelial lesion
      (SIL), endometrial pathology of hyperplasia or higher, adenocarcinoma in situ
      (AIS), or invasive adenocarcinoma. RESULTS: AGUS was diagnosed in 92 of 87,632
      patients (0.11%). FU data were available from 69 patients, consisting of smears
      and/or surgical pathology specimens from the cervix, endometrium, or ovary. Forty
      patients had FU smears only, 13 had histologic FU only, and 16 had both.
      Seventeen patients (25%; 15 patients with unqualified AGUS and 2 patients with
      "favor endometrial origin" according to the Bethesda System of AGUS
      subclassification) had clinically significant lesions: high grade SIL (n = 8
      patients), low grade SIL (n = 2 patients), endometrial lesion (n = 5 patients),
      AIS (n = 1 patient), and invasive cervical adenocarcinoma (n = 1 patient). It is
      noteworthy that 4 patients with carcinoma (3 patients with AIS and 1 patient with
      invasive carcinoma) were diagnosed after a long FU (36-48 months). The remaining
      13 lesions were detected at first FU (1-24 months). Six lesions were detected on
      FU smear, whereas 15 were detected histologically (4 lesions were detected in
      both). CONCLUSIONS: AGUS is associated with clinically significant lesions in 25%
      of patients who are followed. Most of the lesions were high grade and were
      detected histologically. Moreover, 4 of 17 lesions were detected after a FU
      period ranging from 36 months to 48 months. The role of qualifying AGUS needs
      further study. Cancer (Cancer Cytopathol)

PMID- 10966559
TI  - Review of the Bethesda System atlas does not improve reproducibility or accuracy
      in the classification of atypical squamous cells of undetermined significance
      smears.
AB  - BACKGROUND: The Bethesda System (TBS) and its accompanying atlas were developed
      to promote uniform diagnosis and reporting of cervical and vaginal cytology,
      especially with respect to borderline abnormal smears. The authors assessed
      whether group study of TBS atlas improves the reproducibility and accuracy of the
      cytopathologic diagnosis of equivocal Papanicolaou smears. METHODS: One hundred
      "atypical" smears were divided into pretest and posttest sets containing equal
      numbers of negative, atypical squamous cells of undetermined significance
      (ASCUS), and squamous intraepithelial lesion (SIL) diagnoses based on a five
      member panel review. Two comparable teams of four pathologists from George
      Washington University Medical Center (Washington, DC) and Kaiser Permanente
      (Portland, OR), each comprised of two more experienced cytopathologists and two
      less experienced pathologists, independently reviewed the 50 pretest slides and
      classified the slides according to TBS as negative, ASCUS, or SIL. The teams then
      conducted group study sessions using TBS atlas. After the review, the
      pathologists independently classified the 50 posttest slides in a similar manner.
      RESULTS: Pretest, pair-wise interobserver agreement ranged from 30% to 66%
      compared with 34-62% for posttest agreement. Absolute percent agreement of
      reviewers' diagnoses with a previously developed consensus diagnosis based on
      opinions of a five-expert panel (cytopathologic certainty scale) ranged from 44%
      to 62% for the pretest set and from 40% to 60% for the posttest set. Comparison
      of the detection of oncogenic human papilloma virus (HPV) DNA by hybrid capture
      tube test with smears classified as negative, ASCUS, or SIL revealed that seven
      of eight reviewers did not demonstrate a stronger association between HPV
      detection and cytologic diagnosis in the posttest set. CONCLUSIONS: Review of TBS
      atlas by itself does not appear to improve the reproducibility or accuracy of
      cytologic diagnoses. The lack of improvement was similar among the pathologists
      involved regardless of experience level or whether they had a close working
      relation. Cancer (Cancer Cytopathol)

PMID- 10966561
TI  - Trends in the frequency and predictive value of reporting high grade
      abnormalities in cervical smears.
AB  - BACKGROUND: The "organized approach" to cervical screening in Australia includes
      standardized quality assurance measures for laboratories. This study examines
      changes in the frequency and the positive predictive value of reporting severe
      abnormalities in cervical smears over a 3-year period as a guide to the effects
      of implementing these measures. METHODS: The results of screening in 6-month
      periods from January 1995 to December 1997 were determined. Biopsy follow-up for
      results in the high grade epithelial abnormality ("HGEA") and "inconclusive:
      possible HGEA" categories was obtained from the Western Australian Cervical
      Cytology Registry (CCR). RESULTS: Approximately 40,000 smears were examined in
      each 6-month period. The frequencies of reporting HGEA were 0.47%, 0.59%, 0.79%,
      0.85%, and 0.84%, and 0.91% for the study periods (P < 0.001). For the
      inconclusive category, they were 0.24%, 0.18%, 0.24%, 0.31%, 0.38%, and 0.35% (P
      < 0.001). Biopsy follow-up was available for 83. 9%, 80.5%, 89.9%, 92.4%, 93.1%,
      and 90.3% of the HGEA results and for 78.6%, 71.7%, 80.5%, 75.0%, 87.1%, and
      85.9% of the inconclusive results over the study periods. The yield of high grade
      lesions for the biopsied cases was 82.6%, 82.3%, 83.1%, 79.5%, 80.9%, and 79% for
      HGEA cases and 58.2%, 41.9%, 60.6%, 52.8%, 47.5%, and 54.1% for inconclusive
      cases. CONCLUSIONS: There was a doubling in the reporting of HGEA results,
      whereas the positive predictive value for biopsied cases remained at about 80%.
      Reporting rates for inconclusive: possible HGEA cases also doubled, but the yield
      of biopsy-proven, high grade lesions remained at about 50%. These changes
      occurred in the absence of ancillary testing and with targeted rescreening
      methods. A high rate of reporting HGEA, in combination with a high positive
      predictive value, is among the most important indicators of cervical cytology
      laboratory performance. Large improvements in results may occur using
      conventional methods of quality assurance. Cancer (Cancer Cytopathol)

PMID- 10966562
TI  - Subclassifying atypical urinary cytology specimens.
AB  - BACKGROUND: Subclassifying atypical gynecologic Papanicolaou smears successfully
      stratifies patients for risk of a significant underlying lesion. Subclassifying
      atypical urine cytology specimens also may be of value. METHODS: A literature
      review and summary of personal experience with urine cytology specimens were
      performed. RESULTS: Although a wide range of atypical urinary specimens exists,
      most can be categorized into a limited number of patterns. Different patterns are
      associated with different levels of risk for either low grade or high grade
      urothelial neoplasms. CONCLUSIONS: Subclassification of urinary cytology
      specimens may be of value in stratifying patients for their risk of either low
      grade or high grade urothelial carcinoma. Awareness of these patterns may aid in
      evaluating urinary cytology specimens. Cancer (Cancer Cytopathol)

PMID- 10966563
TI  - Diagnostic value of a second generation CA 15-3 antibody to detect adenocarcinoma
      in body cavity effusions.
AB  - BACKGROUND: Detecting malignant cells in body cavity effusions can be
      diagnostically challenging. Several monoclonal antibodies have been studied to
      improve the diagnostic yield of effusion cytology but without widespread
      acceptance. The CA 15-3 antibody has demonstrated high sensitivity but limited
      specificity for breast carcinoma in surgical pathology. A second generation CA 15
      3 antibody has been developed that has not been studied in serous effusions to
      the authors' knowledge. The authors examined this second generation CA 15-3
      antibody for its diagnostic utility in detecting adenocarcinomas in this
      cytologic setting. METHODS: Cell block material from 114 cases of unequivocally
      benign or malignant body cavity effusions were studied. Slides were stained for
      CA 15-3 by using the avidin-biotin complex method. The percentage of cells
      exhibiting strong staining was estimated both for breast carcinoma and for all
      adenocarcinomas as a group. These results were compared with CA 15-3 staining
      exhibited by benign mesothelium. RESULTS: CA 15-3 was expressed in at least 10%
      of tumor cells in 97% of breast carcinoma cases and in 90% of adenocarcinomas
      overall. The highest sensitivity was observed in carcinomas of the breast, ovary,
      and lung. Of 40 cases of benign mesothelium, only 4 (10%) were positive (P <
      0.001). The sensitivity of CA 15-3 was 97% for breast carcinoma and 91% for
      adenocarcinomas overall. Specificity was 95% for breast carcinoma and 91% for
      adenocarcinomas. CONCLUSIONS: CA 15-3 is an immunostain with high specificity and
      sensitivity for adenocarcinomas in cell block material from effusions. The
      antibody holds particular promise for detecting breast carcinoma. Cancer (Cancer
      Cytopathol)

PMID- 10966564
TI  - Telomerase activity as a marker of breast carcinoma in fine-needle aspirated
      samples.
AB  - BACKGROUND: Telomerase activity in breast fine-needle aspiration (FNA) samples
      may have diagnostic utility. The purpose of this study was to compare in FNA
      samples of breast tumor the diagnostic accuracy as correlated with histologic
      final diagnosis. METHODS: Fine-needle aspiration samples were obtained from 617
      patients with palpable breast tumors. Slide preparation and cytology were
      performed according to a uniform approach. Extracts derived from 10(3) cells from
      the residual cells in the syringe were used for the telomeric repeat
      amplification protocol (TRAP) assay. Of the original 617 patients, 220 underwent
      open biopsy or surgery, and 93 cancers and 127 patients' benign diseases were
      diagnosed by histologic examination. RESULTS: All 62 tumors that were diagnosed
      as "malignant" or "probably malignant" by FNA cytology were cancerous, and 50
      cases (81%) showed detectable telomerase activity. Among 17 "atypical" or
      "indeterminate" cases, all 10 tumors with detectable telomerase activity
      subsequently were diagnosed as breast carcinoma whereas 6 of 7 tumors without
      telomerase activity were diagnosed as benign. Among the 141 "benign" or
      "unsatisfactory" samples, 12 of 21 cases with detectable telomerase activity
      subsequently were diagnosed as cancer. CONCLUSIONS: The diagnostic accuracy of
      telomerase activity in FNA samples is considered to be equivalent or slightly
      higher to that of cytology (86% vs. 70%). Detection of telomerase activity should
      be considered an alert for false-negative results of FNA cytology and may be
      useful as a diagnostic marker for breast malignancy, especially in samples
      cytologically undetermined to be malignant. Cancer (Cancer Cytopathol)

PMID- 10966565
TI  - Fine-needle aspiration of the thyroid.
AB  - BACKGROUND: Although fine-needle aspiration (FNA) of the thyroid is the key
      preoperative investigation of thyroid lesions, there are overlaps in the criteria
      for diagnosis of certain lesions, particularly important among which are those
      for follicular neoplasms. A proposal for a 5-category working system for thyroid
      FNA diagnosis is presented, devised using clearly defined diagnostic guidelines
      with a prospective 2-year evaluation in 1 center. METHODS: The results of FNA of
      156 patients with nodular thyroid lesions are presented. All patients were
      observed over a 2-year period in a multidisciplinary thyroid clinic. In some
      cases, the aspirates were repeated before excision of the lesion. The results of
      the FNA are classified by worst category for each patient, according to a 5
      category scheme: THY1: inadequate; THY2: benign; THY3: indeterminate; THY4:
      suspicious lesion; THY5: malignant. RESULTS: Seventy-five of the 156 patients
      (48.1%) proceeded to excision, of these 50 (67%) showed multinodular goiter or
      adenomatoid nodule within a goiter, 7 (9.3%) showed evidence of Hashimoto
      thyroiditis or lymphocytic thyroiditis alone, 1 (1.3%) showed evidence of Reidel
      thyroiditis, and 1 (1.3%) showed evidence of a parathyroid cyst. Eight patients
      (11%) showed evidence of follicular adenoma, and 5 patients (6.6%) showed
      papillary carcinoma; 1 (1.3%) showed follicular carcinoma, and 2 (2.7%) showed
      lymphoproliferative disease. There was a significant difference in the number of
      benign as compared with neoplastic thyroid lesions excised in the indeterminate
      (THY3) (2 of 13 [15%]) as compared with the suspicious categories (THY4) (10 of
      24 [42%]), (P = 0.05). Although no false-negative FNAs were identified in this
      series, there was 1 false-positive (THY5) FNA. CONCLUSIONS: The use of an
      indeterminate (THY3) category is helpful because it improves the diagnostic
      efficacy of thyroid FNA. The indeterminate (THY3) category is clinically useful
      and may markedly reduce or eliminate false-negative FNA in many patients with
      thyroid nodules. Cancer (Cancer Cytopathol)

PMID- 10966566
TI  - Aspiration cytopathology of epithelioid angiosarcoma.
AB  - BACKGROUND: Epithelioid angiosarcoma (EA) is an uncommon neoplasm readily
      mistaken for carcinoma. In contrast to the histopathology of this tumor, the
      cytopathology as obtained using fine-needle aspiration (FNA) biopsy has rarely
      been described. METHODS: Three patients with histologically and
      immunohistochemically proven EA each underwent FNA using standard technique
      before surgical resection. RESULTS: Aspirate smears were obtained from 3 males
      (ages 47, 63, and 15 years) each of whom presented with a solitary palpable soft
      tissue mass, 1 from the left calf and 2 from the right popliteal region. No
      patient had a history of malignancy or had been exposed to prior radiation
      therapy. Smears were relatively hypocellular due to the dilutional effects of
      abundant blood. Cells were scattered on slides primarily in a single cell
      dissociated pattern; small aggregates were present in a fraction of the slides.
      Malignant cells generally monotonous in size and averaging three to four times
      the dimension of a mature lymphocyte had a rounded so-called epithelioid
      configuration. Cells possessed primarily rounded, single nuclei often
      eccentrically placed, with some anisokaryosis, and smooth nuclear borders.
      Binucleated cells with mirror-image nuclei were much less frequent, and cells
      with three or four nuclei were even more scarce. Cells contained large single
      nucleoli or more often multiple misshapen smaller nucleoli. Cytoplasm was
      abundant and finely granular in virtually all cells. In some, the cytoplasm
      acquired a central spheric density thus producing a "rhabdoid" appearance that
      was only seen with air-dried Diff-Quik (Fisher Scientific, Biochemical Sciences,
      Inc., Swedesboro, NJ) stained smears. Mitoses were readily found. Immunostaining
      of the cell block in one case permitted a specific diagnosis of EA before
      subsequent surgical excision. CONCLUSIONS: Epithelioid angiosarcoma may display a
      rhabdoid morphology in FNA biopsy smears, and this cytopathology can closely
      mimic that of nonsmall carcinoma, malignant melanoma, and other epithelioid types
      of soft tissue tumors. Immunophenotyping is essential for definitive diagnosis.
      Cancer (Cancer Cytopathol)

PMID- 10966567
TI  - Tyrosinase immunoreactivity in fine-needle aspiration samples of metastatic
      malignant melanoma.
AB  - BACKGROUND: Tyrosinase, the rate-limiting enzyme in melanin synthesis, is a
      melanoma associated antigen that is recognized by both CD4+ and CD8+ T-cells in
      an HLA-restricted fashion. Peptides derived from the tyrosinase antigen currently
      are being utilized as a target for T-cells in several immunotherapy protocols for
      metastatic malignant melanoma (MMM) at the National Institutes of Health/National
      Cancer Institute. Serial fine-needle aspirations of metastatic lesions are
      performed to monitor the antigen expression of tyrosinase during treatment by
      immunostaining cytologic preparations with the monoclonal antibody T311. METHODS:
      In the current study, 62 samples of MMM were evaluated for tyrosinase
      immunoreactivity on air-dried, acetone fixed cytospins and the corresponding
      formalin fixed, paraffin embedded cell block using an avidin-biotin
      immunoperoxidase method. RESULTS: Positive immunoreactivity revealed a granular
      cytoplasmic staining in melanocytic cells. The current study results showed that
      92% of samples (57 of 62) were T311 immunoreactive on cell block preparations,
      whereas only 61% (38 of 62) were immunoreactive on cytospin preparations. In 66%
      of samples (41 of 62) immunoreactivity for T311 was greater in the cell block
      sample than in the corresponding cytospin, whereas in only 3% of samples (2 of
      62) was it greater in the cytospins. In 31% of samples (19 of 62) there was no
      significant difference in immunoreactivity between the 2 sample types.
      CONCLUSIONS: The results of the current study show that tyrosinase is a sensitive
      marker for the detection of MMM; however, the optimal method of sample
      preparation for immunoperoxidase staining appears to be formalin fixation and
      paraffin embedding as tyrosinase immunoreactivity is diminished significantly in
      air-dried cytospin samples despite subsequent acetone fixation. Cancer (Cancer
      Cytopathol)

PMID- 10966568
TI  - Application of the p53 and K-ras gene mutation patterns for cytologic diagnosis
      of recurrent lung carcinomas.
AB  - BACKGROUND: Cytologic specimens are one of the most important materials for lung
      carcinoma diagnosis, because they can be used in mass screening for lung
      carcinoma and early detection of cancer recurrence by examination of sputum and
      pleural fluid. METHODS: To prove the potentiality of the cytologic specimens to
      be subjected to molecular detection of recurrent lung carcinomas, the authors
      enrolled 16 patients who had undergone surgical treatment for lung carcinoma with
      recurrence detected by malignant pleural fluid. First, they examined K-ras gene
      and p53 tumor suppressor gene abnormalities in resected tumors by polymerase
      chain reaction-based single-strand conformation polymorphism (PCR-SSCP) analysis.
      Next, using a microdissection method, they investigated the use of cytologic
      specimens such as pleural fluid for the detection of recurrence by finding the
      same mutations observed in the initially resected tumor. RESULTS: Seven
      abnormally shifted bands were detected among six patients by PCR-SSCP analysis of
      surgical materials. Five of 7 abnormally shifted bands (71.4%) also were detected
      from microdissected malignant cells in cytologic smears. In two cases, they
      detected mutations by using single malignant cells in pleural fluid. CONCLUSIONS:
      The authors successfully detected the same mutations in recurrent cytologic
      specimens as those in the initially resected tumors by PCR-SSCP analysis. These
      findings suggest that the p53 and K-ras gene mutation patterns are effective
      markers for the detection of recurrent lung carcinoma in cytologic specimens.
      Cancer (Cancer Cytopathol)

PMID- 10966569
TI  - How to generate improved potentials for protein tertiary structure prediction: a
      lattice model study.
AB  - Success in the protein structure prediction problem relies heavily on the choice
      of an appropriate potential function. One approach toward extracting these
      potentials from a database of known protein structures is to maximize the Z-score
      of the database proteins, which represents the ability of the potential to
      discriminate correct from random conformations. These optimization methods model
      the entire distribution of alternative structures, reducing their ability to
      concentrate on the lowest energy structures most competitive with the native
      state and resulting in an unfortunate tendency to underestimate the repulsive
      interactions. This leads to reduced accuracy and predictive ability. Using a
      lattice model, we demonstrate how we can weight the distribution to suppress the
      contributions of the high-energy conformations to the Z-score calculation. The
      result is a potential that is more accurate and more likely to yield correct
      predictions than other Z-score optimization methods as well as potentials of mean
      force.

PMID- 10966570
TI  - Glucose-6-phosphate transporter and receptor functions of the glucose 6
      phosphatase system analyzed from a consensus defined by multiple alignments.
AB  - The cDNA encoding the protein (P46) that is mutated in glycogen storage disease
      type-1b (GSD-1b) has been previously cloned by homology with bacterial sequences
      of the uhp (upper hexose phosphate) system. Hydropathic profiles, transmembrane
      prediction analysis, and a multiple alignment of 14 sequences related to P46
      (with percentage of identity around 30%) allowed to identify two large domains in
      the proteins linked by a large variable loop. Highly conserved transmembrane (TM)
      segments, TM1 and TM4 in the first domain and TM5 in the second one, were
      identified almost in all the integral proteins related to P46. The multiple
      alignment allowed definition of a consensus involving the 14 sequences related to
      P46. The detailed comparison of the consensus with the UhpT (the bacterial G6P
      transporter) and with UhpC (the bacterial G6P receptor) sequences reveals that
      the P46 protein could carry both G6P receptor and transporter functions.

PMID- 10966571
TI  - DARWIN: a program for docking flexible molecules.
AB  - A new program named "DARWIN" has been developed to perform docking calculations
      with proteins and other biological molecules. The program uses the Genetic
      Algorithm to optimize the molecule's conformation and orientation under the
      selective pressure of minimizing the potential energy of the complex. A unique
      feature of DARWIN is that it communicates with the molecular mechanics program
      CHARMM to make the energy calculations. A second important feature is its
      parallel interface, which allows simultaneous use of multiple stand-alone copies
      of CHARMM to rapidly evaluate large numbers of potential solutions. This permits
      an "accuracy first" approach to docking, which avoids many of the common
      assumptions and shortcuts often made to reduce computation time. The method was
      applied to three protein-carbohydrate complexes: the crystallographically
      determined structures of Concanavalin A and Fab Se155-4; and a model structure
      for Fab ME36.1. Conformations close to the crystal structures were obtained with
      this approach, but some "false positive" solutions were also selected. Many of
      these could be eliminated by introducing different methods for simulating solvent
      effects. An effective screening method for docking a database of compounds to a
      single target enzyme using DARWIN is also presented.

PMID- 10966572
TI  - Comparison of two optimization methods to derive energy parameters for protein
      folding: perceptron and Z score.
AB  - Two methods were proposed recently to derive energy parameters from known native
      protein conformations and corresponding sets of decoys. One is based on finding,
      by means of a perceptron learning scheme, energy parameters such that the native
      conformations have lower energies than the decoys. The second method maximizes
      the difference between the native energy and the average energy of the decoys,
      measured in terms of the width of the decoys' energy distribution (Z-score).
      Whereas the perceptron method is sensitive mainly to "outlier" (i.e., extremal)
      decoys, the Z-score optimization is governed by the high density regions in decoy
      space. We compare the two methods by deriving contact energies for two very
      different sets of decoys: the first obtained for model lattice proteins and the
      second by threading. We find that the potentials derived by the two methods are
      of similar quality and fairly closely related. This finding indicates that
      standard, naturally occurring sets of decoys are distributed in a way that yields
      robust energy parameters (that are quite insensitive to the particular method
      used to derive them). The main practical implication of this finding is that it
      is not necessary to fine-tune the potential search method to the particular set
      of decoys used.

PMID- 10966573
TI  - Functional aspects of the heme bound hemophore HasA by structural analysis of
      various crystal forms.
AB  - The protein HasA from the Gram negative bacteria Serratia marcescens is the first
      hemophore to be described at the molecular level. It participates to the
      shuttling of heme from hemoglobin to the outer membrane receptor HasR, which in
      turn releases it into the bacterium. HasR alone is also able to take up heme from
      hemoglobin but synergy with HasA increases the efficiency of the system by a
      factor of about 100. This iron acquisition system allows the bacteria to survive
      with hemoglobin as the sole iron source. Here we report the structures of a new
      crystal form of HasA diffracting up to 1.77A resolution as well as the refined
      structure of the trigonal crystal form diffracting to 3.2A resolution. The
      crystal structure of HasA at high resolution shows two possible orientations of
      the heme within the heme-binding pocket, which probably are functionally involved
      in the heme-iron acquisition process. The detailed analysis of the three known
      structures reveals the molecular basis regulating the relative affinity of the
      heme/hemophore complex.

PMID- 10966574
TI  - Dipole lattice membrane model for protein calculations.
AB  - A dipole lattice model for lipid membranes and their interactions with peptides
      is presented. It uses the Langevin dipole method to calculate electrostatic
      interactions in the heterogeneous membrane environment. A series of test cases
      are presented, including spherical charges, dipoles, side chain analogs, and
      helical peptides. The model consistently produces qualitatively correct results.

PMID- 10966575
TI  - Rapid automatic detection and alignment of repeats in protein sequences.
AB  - Many large proteins have evolved by internal duplication and many internal
      sequence repeats correspond to functional and structural units. We have developed
      an automatic algorithm, RADAR, for segmenting a query sequence into repeats. The
      segmentation procedure has three steps: (i) repeat length is determined by the
      spacing between suboptimal self-alignment traces; (ii) repeat borders are
      optimized to yield a maximal integer number of repeats, and (iii) distant repeats
      are validated by iterative profile alignment. The method identifies short
      composition biased as well as gapped approximate repeats and complex repeat
      architectures involving many different types of repeats in the query sequence. No
      manual intervention and no prior assumptions on the number and length of repeats
      are required. Comparison to the Pfam-A database indicates good coverage, accurate
      alignments, and reasonable repeat borders. Screening the Swissprot database
      revealed 3,000 repeats not annotated in existing domain databases. A number of
      these repeats had been described in the literature but most were novel. This
      illustrates how in times when curated databases grapple with ever increasing
      backlogs, automatic (re)analysis of sequences provides an efficient way to
      capture this important information.

PMID- 10966576
TI  - The synthetase domains of cobalamin biosynthesis amidotransferases cobB and cobQ
      belong to a new family of ATP-dependent amidoligases, related to dethiobiotin
      synthetase.
AB  - Phosphotransacetylases of Escherichia coli and several other bacteria contain an
      additional 350-aa N-terminal fragment that is not required for
      phosphotransacetylase activity. Sequence analysis of this fragment revealed that
      it is closely related to a family of ATP-dependent enzymes that also includes
      dethiobiotin synthetase and the synthetase domains of two amidotransferases
      involved in cobalamin biosynthesis, cobyrinic acid a,c-diamide synthase (CobB)
      and cobyric acid synthase (CobQ). Further database searches showed that this
      enzyme family is also related to the MinD family of ATPases involved in
      regulation of cell division in bacteria and archaea. Analysis of sequence
      conservation in the members of this enzyme family using the structure of
      dethiobiotin synthetase active site as a guide allowed us to suggest a model for
      the interaction of CobB and CobQ with their respective substrates. CobB and CobQ
      were also found to contain unusual Triad family (class I) glutamine
      amidotransferase domains with conserved Cys and His residues, but lacking the Glu
      residue of the catalytic triad. These results should help in understanding the
      enzymology of cobalamin biosynthesis and in resolving the role of
      phosphotransacetylase in regulation of the carbon flow to and from acetate.

PMID- 10966577
TI  - An analysis of the helix-to-strand transition between peptides with identical
      sequence.
AB  - An analysis of peptide segments with identical sequence but that differ
      significantly in structure was performed over non-redundant databases of protein
      structures. We focus on those peptides, which fold into an alpha-helix in one
      protein but a beta-strand in another. While the study shows that many such
      structurally ambivalent peptides contain amino acids with a strong helical
      preference collocated with amino acids with a strong strand preference, the
      results overwhelmingly indicate that the peptide's environment ultimately
      dictates its structure. Furthermore, the first naturally occurring structurally
      ambivalent nonapeptide from evolutionary unrelated proteins is described,
      highlighting the intrinsic plasticity of peptide sequences. We even find seven
      proteins that show structural ambivalence under different conditions. Finally, a
      computer algorithm has been implemented to identify regions in a given sequence
      where secondary structure prediction programs are likely to make serious
      mispredictions.

PMID- 10966578
TI  - Comparative modeling of the three-dimensional structures of family 3 glycoside
      hydrolases.
AB  - There are approximately 100 known members of the family 3 group of glycoside
      hydrolases, most of which are classified as beta-glucosidases and originate from
      microorganisms. The only family 3 glycoside hydrolase for which a three
      dimensional structure is available is a beta-glucan exohydrolase from barley. The
      structural coordinates of the barley enzyme is used here to model representatives
      from distinct phylogenetic clusters within the family. The majority of family 3
      hydrolases have an NH(2)-terminal (alpha/beta)(8) barrel connected by a short
      linker to a second domain, which adopts an (alpha/beta)(6) sandwich fold. In two
      bacterial beta-glucosidases, the order of the domains is reversed. The catalytic
      nucleophile, equivalent to D285 of the barley beta-glucan exohydrolase, is
      absolutely conserved across the family. It is located on domain 1, in a shallow
      site pocket near the interface of the domains. The likely catalytic acid in the
      barley enzyme, E491, is on domain 2. Although similarly positioned acidic
      residues are present in closely related members of the family, the equivalent
      amino acid in more distantly related members is either too far from the active
      site or absent. In the latter cases, the role of catalytic acid is probably
      assumed by other acidic amino acids from domain 1.

PMID- 10966580
TI  - Heart attacks without chest pain: the danger is greater.

PMID- 10966579
TI  - Triglycerides and heart disease.

PMID- 10966582
TI  - Ask the doctor. My chest x-ray report said that I had an "uncoiling aorta." My
      doctor told me that it just means that my aorta is getting longer as I am getting
      older and that it was normal. But if it was normal, why did they mention it in
      the report?

PMID- 10966581
TI  - Don't give up on fiber.

PMID- 10966583
TI  - Ask the doctor. Recently I read that aspirin can actually increase a person's
      risk for a stroke by causing bleeding in the brain. I have atrial fibrillation
      and my doctor wants me to take a blood thinner - if not warfarin, then at least
      aspirin. I've already had a heart attack and I don't want to run the risk of a
      stroke, so I have refused. What should I do?

PMID- 10966584
TI  - Alternative medicine.

PMID- 10966585
TI  - Depression. Five new treatments.

PMID- 10966586
TI  - Respiratory disease. Asthma update.

PMID- 10966587
TI  - Infectious disease. Rabies.

PMID- 10966588
TI  - By the way, doctor... Should I get rotator cuff surgery?

PMID- 10966589
TI  - Attention deficit disorder - part II.

PMID- 10966591
TI  - Exercise as psychotherapy.

PMID- 10966590
TI  - Depression late in life.

PMID- 10966592
TI  - Depression as a physical illness.

PMID- 10966593
TI  - Aging and personality.

PMID- 10966594
TI  - Forum. How much therapy is enough?

PMID- 10966595
TI  - That lingering cough. Part I: introduction.

PMID- 10966596
TI  - The life of a plaque: what causes heart attacks.

PMID- 10966597
TI  - Water.

PMID- 10966598
TI  - On call. I am 46 years old and have arthritis of my knees. Ibuprofen helps, but I
      still have pain. Should I consider the new joint injections?

PMID- 10966599
TI  - Women, work, and stress.

PMID- 10966600
TI  - Hormone replacement. HRT forum: progestins.

PMID- 10966601
TI  - Shingles vaccine trial underway.

PMID- 10966602
TI  - Vision. Cataract removal: getting a clearer view.

PMID- 10966603
TI  - By the way, doctor. I recently read that this year's flu vaccine is recommended
      for anyone over the age of 50. Why has the age changed from 65 to 50?

PMID- 10966604
TI  - A debate over fMRI data sharing.

PMID- 10966606
TI  - Does a stretch-inactivated cation channel integrate osmotic and peptidergic
      signals?

PMID- 10966605
TI  - Does a stretch-inactivated cation channel integrate osmotic and peptidergic
      signals?

PMID- 10966607
TI  - Distant synapses raise their voices.

PMID- 10966608
TI  - CNTF II, I presume?

PMID- 10966609
TI  - Probing the olfactory code.

PMID- 10966610
TI  - Coding for visual categories in the human brain.

PMID- 10966611
TI  - The mechanics behind spines on the move

PMID- 10966612
TI  - Thinking about feeling

PMID- 10966613
TI  - Fast synaptic fatigue in shibire mutants reveals a rapid requirement for dynamin
      in synaptic vesicle membrane trafficking.
AB  - The GTPase dynamin is involved in endocytosis in many cell types, as first
      revealed by temperature-sensitive paralytic mutations in the Drosophila dynamin
      gene, shibire (shi), which disrupt synaptic vesicle endocytosis and deplete
      synaptic terminals of vesicles. Here we report that shi synapses exhibit a fast
      synaptic fatigue phenotype within 20 ms of repetitive stimulation, which cannot
      be explained by vesicle depletion, as we confirmed by electron microscopy. These
      results suggest that, in addition to its well-characterized role in synaptic
      vesicle recycling, dynamin may be required for short-term maintenance of the
      readily releasable pool of synaptic vesicles.

PMID- 10966614
TI  - Motor timing learned without motor training.
AB  - Improvements due to perceptual training are often specific to the trained task
      and do not generalize to similar perceptual tasks. Surprisingly, given this
      history of highly constrained, context-specific perceptual learning, we found
      that training on a perceptual task showed significant transfer to a motor task.
      This result provides evidence for a common neural architecture underlying
      analysis of sensory input and control of motor output, and suggests a potential
      role for perception in motor development and rehabilitation.

PMID- 10966615
TI  - Should the neuroscience community make a paradigm shift to sharing primary data?
AB  - The author outlines the pros and cons of data sharing for neuroscientists and
      argues that continued progress in the field will depend on a cultural shift
      toward making primary data freely available. He argues in favor of distributed
      databases to maximize the efficient use of data.

PMID- 10966616
TI  - CLF associates with CLC to form a functional heteromeric ligand for the CNTF
      receptor complex.
AB  - Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation
      and survival of various cell types in the peripheral and central nervous systems.
      Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two
      signaling beta chains, gp130 and the leukemia inhibitory factor receptor (LIFR).
      Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest
      that CNTFR serves as a receptor for a second, developmentally important ligand.
      We have identified this factor as a stable secreted complex of cardiotrophin-like
      cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF
      expression was required for CLC secretion, and the complex acted only on cells
      expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR
      and signal transducer and activator of transcription 3 (STAT3) and supported
      motor neuron survival. Our results indicate that the CLF/CLC complex is a second
      ligand for CNTFR with potentially important implications in nervous system
      development.

PMID- 10966617
TI  - Control of Muller glial cell proliferation and activation following retinal
      injury.
AB  - Muller glial cells are the major support cell for neurons in the vertebrate
      retina. Following neuronal damage, Muller cells undergo reactive gliosis, which
      is characterized by proliferation and changes in gene expression. We have found
      that downregulation of the tumor supressor protein p27Kip1 and re-entry into the
      cell cycle occurs within the first 24 hours after retinal injury. Shortly
      thereafter, Muller glial cells upregulate genes typical of gliosis and then
      downregulate cyclin D3, in concert with an exit from mitosis. Mice lacking
      p27Kip1 showed a constitutive form of reactive gliosis, which leads to retinal
      dysplasia and vascular abnormalities reminiscent of diabetic retinopathy. We
      conclude that p27Kip1 regulates Muller glial cell proliferation during reactive
      gliosis.

PMID- 10966618
TI  - Molecular memory by reversible translocation of calcium/calmodulin-dependent
      protein kinase II.
AB  - Synaptic plasticity is thought to be a key process for learning, memory and other
      cognitive functions of the nervous system. The initial events of plasticity
      require the conversion of brief electrical signals into alterations of the
      biochemical properties of synapses that last for much longer than the initial
      stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin
      dependent protein kinase IIalpha (CaMKII), sequentially translocates to
      postsynaptic sites, undergoes autophosphorylation and gets trapped for several
      minutes until its dissociation is induced by secondary autophosphorylation and
      phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation
      for several minutes. This suggests that trapping of CaMKII by its targets and
      priming of CaMKII translocation may function as biochemical memory mechanisms
      that change the signaling capacity of synapses.

PMID- 10966619
TI  - Glutamate receptors regulate actin-based plasticity in dendritic spines.
AB  - Dendritic spines at excitatory synapses undergo rapid, actin-dependent shape
      changes which may contribute to plasticity in brain circuits. Here we show that
      actin dynamics in spines are potently inhibited by activation of either AMPA or
      NMDA subtype glutamate receptors. Activation of either receptor type inhibited
      actin-based protrusive activity from the spine head. This blockade of motility
      caused spines to round up so that spine morphology became both more stable and
      more regular. Inhibition of spine motility by AMPA receptors was dependent on
      postsynaptic membrane depolarization and influx of Ca 2+ through voltage
      activated channels. In combination with previous studies, our results suggest a
      two-step process in which spines initially formed in response to NMDA receptor
      activation are subsequently stabilized by AMPA receptors.

PMID- 10966620
TI  - Somatic EPSP amplitude is independent of synapse location in hippocampal
      pyramidal neurons.
AB  - Most neurons receive thousands of synaptic inputs onto widely spread dendrites.
      Because of dendritic filtering, distant synapses should have less efficacy than
      proximal ones. To investigate this, we characterized the amplitude and kinetics
      of excitatory synaptic input across the apical dendrites of CA1 pyramidal neurons
      using dual whole-cell recordings. We found that dendritic EPSP amplitude
      increases with distance from the soma, counterbalancing the filtering effects of
      the dendrites and reducing the location dependence of somatic EPSP amplitude.
      Dendritic current injections and a multi-compartmental computer model
      demonstrated that dendritic membrane properties have only a minor role in
      elevating the local EPSP. Instead a progressive increase in synaptic conductance
      seems to be primarily responsible for normalizing the amplitudes of individual
      inputs.

PMID- 10966621
TI  - A network of electrically coupled interneurons drives synchronized inhibition in
      neocortex.
AB  - The neocortex has at least two different networks of electrically coupled
      inhibitory interneurons: fast-spiking (FS) and low-threshold-spiking (LTS) cells.
      Agonists of metabotropic glutamate or acetylcholine receptors induced
      synchronized spiking and membrane fluctuations, with irregular or rhythmic
      patterns, in networks of LTS cells. LTS activity was closely correlated with
      inhibitory postsynaptic potentials in neighboring FS interneurons and excitatory
      neurons. Synchronized LTS activity required electrical synapses, but not fast
      chemical synapses. Tetanic stimulation of local circuitry induced effects similar
      to those of metabotropic agonists. We conclude that an electrically coupled
      network of LTS interneurons can mediate synchronized inhibition when activated by
      modulatory neurotransmitters.

PMID- 10966622
TI  - The role of alpha-CaMKII autophosphorylation in neocortical experience-dependent
      plasticity.
AB  - Calcium/calmodulin kinase type II (CaMKII) is a major postsynaptic density
      protein. CaMKII is postulated to act as a 'molecular switch', which, when
      triggered by a transient rise in calcium influx, becomes active for prolonged
      periods because of its ability to autophosphorylate. We studied experience
      dependent plasticity in the barrel cortex of mice carrying a point mutation of
      the alpha-CaMKII gene (T286A), which abolishes this enzyme's ability to
      autophosphorylate. Plasticity was prevented in adult and adolescent mice
      homozygous for the mutation, but was normal in heterozygotes and wild-type
      littermates. These results provide evidence that the molecular switch hypothesis
      is valid for neocortical experience-dependent plasticity.

PMID- 10966623
TI  - Competitive Hebbian learning through spike-timing-dependent synaptic plasticity.
AB  - Hebbian models of development and learning require both activity-dependent
      synaptic plasticity and a mechanism that induces competition between different
      synapses. One form of experimentally observed long-term synaptic plasticity,
      which we call spike-timing-dependent plasticity (STDP), depends on the relative
      timing of pre- and postsynaptic action potentials. In modeling studies, we find
      that this form of synaptic modification can automatically balance synaptic
      strengths to make postsynaptic firing irregular but more sensitive to presynaptic
      spike timing. It has been argued that neurons in vivo operate in such a balanced
      regime. Synapses modifiable by STDP compete for control of the timing of
      postsynaptic action potentials. Inputs that fire the postsynaptic neuron with
      short latency or that act in correlated groups are able to compete most
      successfully and develop strong synapses, while synapses of longer-latency or
      less-effective inputs are weakened.

PMID- 10966625
TI  - Fixation neurons in the superior colliculus encode distance between current and
      desired gaze positions.
AB  - A visual scene is scrutinized during sequential periods of steady fixation,
      connected by saccades that shift the visual axis (gaze) to new positions. During
      such exploratory scan paths, gaze frequently strays from and then returns to
      salient features. How the brain keeps track of major end-goals and intermediate
      subgoals is not understood. We studied the discharge of fixation neurons of the
      brainstem's superior colliculus during multiple-step gaze shifts composed of a
      sequence of saccades made in the dark and separated by short periods of steady
      fixation. Cells were initially silent. As sequential gaze saccades approached the
      goal, firing began; its frequency increased progressively and peaked when gaze
      was on the remembered target location. We conclude that these fixation neurons
      encode the error between desired and actual gaze positions, irrespective of
      trajectory characteristics.

PMID- 10966624
TI  - Multi-unit recordings reveal context-dependent modulation of synchrony in odor
      specific neural ensembles.
AB  - We used neural ensemble recording to examine odor-evoked ensemble patterns in the
      moth antennal (olfactory) lobe. Different odors are thought to evoke unique
      spatiotemporal patterns of glomerular activity, but little is known about the
      population dynamics underlying formation of these patterns. Using a silicon
      multielectrode array, we observed dynamic network interactions within and between
      glomeruli. Whereas brief odor pulses repeatedly triggered activity in the same
      coding ensemble, the temporal pattern of synchronous activity superimposed on the
      ensemble was neither oscillatory nor odor specific. Rather, synchrony strongly
      depended on contextual variables such as odor intensity and intermittency. Also,
      because of emergent inhibitory circuit interactions, odor blends evoked temporal
      ensemble patterns that could not be predicted from the responses to the
      individual odorants. Thus even at this early stage of information processing, the
      timing of odor-evoked neural representations is modulated by key stimulus factors
      unrelated to the molecular identity of the odor.

PMID- 10966626
TI  - Activity in primary visual cortex predicts performance in a visual detection
      task.
AB  - Visual attention can affect both neural activity and behavior in humans. To
      quantify possible links between the two, we measured activity in early visual
      cortex (V1, V2 and V3) during a challenging pattern-detection task. Activity was
      dominated by a large response that was independent of the presence or absence of
      the stimulus pattern. The measured activity quantitatively predicted the
      subject's pattern-detection performance: when activity was greater, the subject
      was more likely to correctly discern the presence or absence of the pattern. This
      stimulus-independent activity had several characteristics of visual attention,
      suggesting that attentional mechanisms modulate activity in early visual cortex,
      and that this attention-related activity strongly influences performance.

PMID- 10966627
TI  - Category-specific visual responses of single neurons in the human medial temporal
      lobe.
AB  - The hippocampus, amygdala and entorhinal cortex receive convergent input from
      temporal neocortical regions specialized for processing complex visual stimuli
      and are important in the representation and recognition of visual images.
      Recording from 427 single neurons in the human hippocampus, entorhinal cortex and
      amygdala, we found a remarkable degree of category-specific firing of individual
      neurons on a trial-by-trial basis. Of the recorded neurons, 14% responded
      selectively to visual stimuli from different categories, including faces, natural
      scenes and houses, famous people and animals. Based on the firing rate of
      individual neurons, stimulus category could be predicted with a mean probability
      of error of 0.24. In the hippocampus, the proportion of neurons responding to
      spatial layouts was greater than to other categories. Our data provide direct
      support for the role of human medial temporal regions in the representation of
      different categories of visual stimuli.

PMID- 10966628
TI  - Motion distorts visual space: shifting the perceived position of remote
      stationary objects.
AB  - To perceive the relative positions of objects in the visual field, the visual
      system must assign locations to each stimulus. This assignment is determined by
      the object's retinal position, the direction of gaze, eye movements, and the
      motion of the object itself. Here we show that perceived location is also
      influenced by motion signals that originate in distant regions of the visual
      field. When a pair of stationary lines are flashed, straddling but not
      overlapping a rotating radial grating, the lines appear displaced in a direction
      consistent with that of the grating's motion, even when the lines are a
      substantial distance from the grating. The results indicate that motion's
      influence on position is not restricted to the moving object itself, and that
      even the positions of stationary objects are coded by mechanisms that receive
      input from motion-sensitive neurons.

PMID- 10966629
TI  - Structural biology in motion.

PMID- 10966630
TI  - Charting a course through RNA polymerase.

PMID- 10966631
TI  - Two are better than one.

PMID- 10966632
TI  - Conformational changes by synchrotron radiation circular dichroism spectroscopy.

PMID- 10966633
TI  - Killer conformations.

PMID- 10966634
TI  - Picture story. Rhodopsin structure sees the light of day.

PMID- 10966635
TI  - Conformational changes studied by cryo-electron microscopy.
AB  - Biological processes involving movement, such as muscle contraction or the
      opening of an ion channel through a membrane, are mediated through conformational
      changes. These changes often occur in large and flexible macromolecular
      complexes. Cryo-electron microscopy provides a means of capturing different
      conformational states of such assemblies. Even if the resulting density maps are
      at low resolution, they can be combined with atomic structures of subcomplexes or
      isolated components determined by X-ray crystallography or NMR. This review
      presents a brief summary of the principles and recent advances in macromolecular
      structure determination by cryo-electron microscopy.

PMID- 10966636
TI  - Observing single biomolecules at work with the atomic force microscope.
AB  - Progress in the application of the atomic force microscope (AFM) to imaging and
      manipulating biomolecules is the result of improved instrumentation, sample
      preparation methods and image acquisition conditions. Biological membranes can be
      imaged in their native state at a lateral resolution of 0.5-1 nm and a vertical
      resolution of 0. 1-0.2 nm. Conformational changes that are related to functions
      can be resolved to a similar resolution, complementing atomic structure data
      acquired by other methods. The unique capability of the AFM to directly observe
      single proteins in their native environments provides insights into the
      interactions of proteins that form functional assemblies. In addition, single
      molecule force spectroscopy combined with single molecule imaging provides
      unprecedented possibilities for analyzing intramolecular and intermolecular
      forces. This review discusses recent examples that illustrate the power of AFM.

PMID- 10966637
TI  - Stretching single molecules into novel conformations using the atomic force
      microscope.
AB  - A dense network of interconnected proteins and carbohydrates forms the complex
      mechanical scaffold of living tissues. The recently developed technique of single
      molecule force spectroscopy using the atomic force microscope (AFM) has enabled a
      detailed analysis of the force-induced conformations of these molecules and the
      determinants of their mechanical stability. These studies provide some of the
      basic knowledge required to understand the mechanical interactions that define
      all biological organisms.

PMID- 10966638
TI  - Measuring conformational dynamics of biomolecules by single molecule fluorescence
      spectroscopy.
AB  - Dynamic structural changes of macromolecules undergoing biochemical reactions can
      be studied using novel single molecule spectroscopy tools. Recent advances in
      applying such distance and orientation molecular rulers to biological systems are
      reviewed, and future prospects and challenges are discussed.

PMID- 10966639
TI  - The renaissance of fluorescence resonance energy transfer.
AB  - Recent advances in fluorescence resonance energy transfer have led to qualitative
      and quantitative improvements in the technique, including increased spatial
      resolution, distance range, and sensitivity. These advances, due largely to new
      fluorescent dyes, but also to new optical methods and instrumentation, have
      opened up new biological applications.

PMID- 10966640
TI  - Identifying conformational changes with site-directed spin labeling.
AB  - Site-direct spin labeling combined with electron paramagnetic resonance (EPR)
      spectroscopy is a powerful tool for detecting structural changes in proteins.
      This review provides examples that illustrate strategies for interpreting the
      data in terms of specific rearrangements in secondary and tertiary structure. The
      changes in the mobility and solvent accessibility of the spin label side chains,
      and in the distances between spin labels, report (i) rigid body motions of alpha
      helices and beta-strands (ii) relative movements of domains and (iii) changes in
      secondary structure. Such events can be monitored in the millisecond time-scale,
      making it possible to follow structural changes during function. There is no
      upper limit to the size of proteins that can be investigated, and only 50-100
      picomoles of protein are required. These features make site-directed spin
      labeling an attractive approach for the study of structure and dynamics in a wide
      range of systems.

PMID- 10966641
TI  - Protein dynamics from NMR.
AB  - This review surveys recent investigations of conformational fluctuations of
      proteins in solution using NMR techniques. Advances in experimental methods have
      provided more accurate means of characterizing fast and slow internal motions as
      well as overall diffusion. The information obtained from NMR dynamics experiments
      provides insights into specific structural changes or configurational energetics
      associated with function. A variety of applications illustrate that studies of
      protein dynamics provide insights into protein-protein interactions, target
      recognition, ligand binding, and enzyme function.

PMID- 10966642
TI  - Structural basis of dimerization, coactivator recognition and MODY3 mutations in
      HNF-1alpha.
AB  - Maturity-onset diabetes of the young type 3 (MODY3) results from mutations in the
      transcriptional activator hepatocyte nuclear factor-1alpha (HNF-1alpha). Several
      MODY3 mutations target the HNF-1alpha dimerization domain (HNF-p1), which binds
      the coactivator, dimerization cofactor of HNF-1 (DCoH). To define the mechanism
      of coactivator recognition and the basis for the MODY3 phenotype, we determined
      the cocrystal structure of the DCoH-HNF-p1 complex and characterized
      biochemically the effects of MODY3 mutations in HNF-p1. The DCoH-HNF-p1 complex
      comprises a dimer of dimers in which HNF-p1 forms a unique four-helix bundle.
      Through rearrangements of interfacial side chains, a single, bifunctional
      interface in the DCoH dimer mediates both HNF-1alpha binding and formation of a
      competing, transcriptionally inactive DCoH homotetramer. Consistent with the
      structure, MODY3 mutations in HNF-p1 reduce activator function by two distinct
      mechanisms.

PMID- 10966643
TI  - Crystal structures of the photosystem II D1 C-terminal processing protease.
AB  - We report here the first three-dimensional structure of the D1 C-terminal
      processing protease (D1P), which is encoded by the ctpA gene. This enzyme removes
      the C-terminal extension of the D1 polypeptide of photosystem II of oxygenic
      photosynthesis. Proteolytic processing is necessary to allow the light driven
      assembly of the tetranuclear manganese cluster, which is responsible for
      photosynthetic water oxidation. The X-ray structure of the Scenedesmus obliquus
      enzyme has been determined at 1.8 A resolution using the multiwavelength
      anomalous dispersion method. The enzyme is monomeric and is composed of three
      folding domains. The middle domain is topologically homologous to known PDZ
      motifs and is proposed to be the site at which the substrate C-terminus binds.
      The remainder of the substrate likely extends across the face of the enzyme,
      interacting at its scissile bond with the enzyme active site Ser 372 / Lys 397
      catalytic dyad, which lies at the center of the protein at the interface of the
      three domains.

PMID- 10966644
TI  - A glimpse of a possible amyloidogenic intermediate of transthyretin.
AB  - Studies have indicated that partially unfolded states occur under conditions that
      favor amyloid formation by transthyretin (TTR), as well as other amyloidogenic
      proteins. In this study, we used hydrogen exchange measurements to show that
      there is selective destabilization of one half of the beta-sandwich structure of
      TTR under such conditions. This provides more direct information about
      conformational fluctuations than previously available, and will facilitate design
      of future experiments to probe the intermediates critical to amyloid formation.

PMID- 10966645
TI  - The extended and eccentric E-DNA structure induced by cytosine methylation or
      bromination.
AB  - Cytosine methylation or bromination of the DNA sequence d(GGCGCC)2 is shown here
      to induce a novel extended and eccentric double helix, which we call E-DNA. Like
      B-DNA, E-DNA has a long helical rise and bases perpendicular to the helix axis.
      However, the 3'-endo sugar conformation gives the characteristic deep major
      groove and shallow minor groove of A-DNA. Also, if allowed to crystallize for a
      period of time longer than that yielding E-DNA, the methylated sequence forms
      standard A-DNA, suggesting that E-DNA is a kinetically trapped intermediate in
      the transition to A-DNA. Thus, the structures presented here chart a
      crystallographic pathway from B-DNA to A-DNA through the E-DNA intermediate in a
      single sequence. The E-DNA surface is highly accessible to solvent, with waters
      in the major groove sitting on exposed faces of the stacked nucleotides. We
      suggest that the geometry of the waters and the stacked base pairs would promote
      the spontaneous deamination of 5-methylcytosine in the transition mutation of
      dm5C-dG to dT-dA base pairs.

PMID- 10966646
TI  - The structure of the pro-apoptotic protease granzyme B reveals the molecular
      determinants of its specificity.
AB  - Granzyme B is a serine protease of the chymotrypsin fold that mediates cell death
      by cytotoxic lymphocytes. It is a processing enzyme, requiring extended peptide
      substrates containing an Asp residue. The determinants that allow for this
      substrate specificity are revealed in the three-dimensional structure of granzyme
      B in complex with a macromolecular inhibitor. The primary specificity for Asp
      occurs through a side-on interaction with Arg 226, a buried Arg side chain of
      granzyme B. An additional nine amino acids make contact with the substrate and
      define the granzyme B extended substrate specificity profile. The substrate
      determinants found in this structure are shared by other members of this protein
      class and help to reveal the properties that define substrate specificity.

PMID- 10966647
TI  - Structural basis for copper transfer by the metallochaperone for the
      Menkes/Wilson disease proteins.
AB  - The Hah1 metallochaperone protein is implicated in copper delivery to the Menkes
      and Wilson disease proteins. Hah1 and the N-termini of its target proteins belong
      to a family of metal binding domains characterized by a conserved MT/HCXXC
      sequence motif. The crystal structure of Hah1 has been determined in the presence
      of Cu(I), Hg(II), and Cd(II). The 1.8 A resolution structure of CuHah1 reveals a
      copper ion coordinated by Cys residues from two adjacent Hah1 molecules. The
      CuHah1 crystal structure is the first of a copper chaperone bound to copper and
      provides structural support for direct metal ion exchange between conserved
      MT/HCXXC motifs in two domains. The structures of HgHah1 and CdHah1, determined
      to 1.75 A resolution, also reveal metal ion coordination by two MT/HCXXC motifs.
      An extended hydrogen bonding network, unique to the complex of two Hah1
      molecules, stabilizes the metal binding sites and suggests specific roles for
      several conserved residues. Taken together, the structures provide models for
      intermediates in metal ion transfer and suggest a detailed molecular mechanism
      for protein recognition and metal ion exchange between MT/HCXXC containing
      domains.

PMID- 10966648
TI  - Crystal structure of a naturally occurring parallel right-handed coiled coil
      tetramer.
AB  - The crystal structure of a polypeptide chain fragment from the surface layer
      protein tetrabrachion from Staphylothermus marinus has been determined at 1.8 A
      resolution. As proposed on the basis of the presence of 11-residue repeats, the
      polypeptide chain fragment forms a parallel right-handed coiled coil structure.
      Complementary hydrophobic interactions and complex networks of surface salt
      bridges result in an extremely thermostable tetrameric structure with remarkable
      properties. In marked contrast to left-handed coiled coil tetramers, the right
      handed coiled coil reveals large hydrophobic cavities that are filled with water
      molecules. As a consequence, the packing of the hydrophobic core differs markedly
      from that of a right-handed parallel coiled coil tetramer that was designed on
      the basis of left-handed coiled coil structures.

PMID- 10966649
TI  - Tetrameric coiled coil domain of Sendai virus phosphoprotein.
AB  - The high resolution X-ray structure of the Sendai virus oligomerization domain
      reveals a homotetrameric coiled coil structure with many details that are
      different from classic coiled coils with canonical hydrophobic heptad repeats.
      Alternatives to the classic knobs-into-holes packing lead to differences in
      supercoil pitch and diameter that allow water molecules inside the core. This
      open and more hydrophilic structure does not seem to be destabilized by mutations
      that would be expected to disrupt classic coiled coils.

PMID- 10966650
TI  - The orientation of DNA in an archaeal transcription initiation complex.
AB  - RNA polymerase from the hyperthermophile archaeon Pyrococcus furiosus (Pfu) forms
      specific and transcriptionally active complexes with its conjugate transcription
      factors TBP (the archaeal TATA binding protein homolog) and TFB (the archaeal
      homolog of eukaryotic RNA polymerase II and III transcription factors TFIIB and
      Brf) at the Pfu glutamate dehydrogenase promoter. A photochemical crosslinking
      method was used to map the vicinity of the catalytic subunits of Pfu RNA
      polymerase to DNA locations distributed along the polymerase-promoter interface.
      The largest component of this archaeal polymerase is split into two subunits, A'
      and A", whose relatively sharp boundary of DNA crosslinking (probed on the
      transcribed strand) is centered five to six base pairs downstream of the
      transcriptional start site. A strong argument based on this information, on the
      well-defined homology between the core bacterial, archaeal and eukaryotic RNA
      polymerase subunits, and on the recently determined structure of a bacterial RNA
      polymerase specifies the directionality of DNA in the archaeal transcription
      complex and its trajectory downstream of the transcriptional start site.

PMID- 10966651
TI  - Structure and mechanism of the evolutionarily unique plant enzyme chalcone
      isomerase.
AB  - Chalcone isomerase (CHI) catalyzes the intramolecular cyclization of chalcone
      synthesized by chalcone synthase (CHS) into (2S)-naringenin, an essential
      compound in the biosynthesis of anthocyanin pigments, inducers of Rhizobium
      nodulation genes, and antimicrobial phytoalexins. The 1.85 A resolution crystal
      structure of alfalfa CHI in complex with (2S)-naringenin reveals a novel open
      faced beta-sandwich fold. Currently, proteins with homologous primary sequences
      are found only in higher plants. The topology of the active site cleft defines
      the stereochemistry of the cyclization reaction. The structure and mutational
      analysis suggest a mechanism in which shape complementarity of the binding cleft
      locks the substrate into a constrained conformation that allows the reaction to
      proceed with a second-order rate constant approaching the diffusion controlled
      limit. This structure raises questions about the evolutionary history of this
      structurally unique plant enzyme.

PMID- 10966652
TI  - Structure of the tetrameric restriction endonuclease NgoMIV in complex with
      cleaved DNA.
AB  - The crystal structure of the NgoMIV restriction endonuclease in complex with
      cleaved DNA has been determined at 1.6 A resolution. The crystallographic
      asymmetric unit contains a protein tetramer and two DNA molecules cleaved at
      their recognition sites. This is the first structure of a tetrameric restriction
      enzyme-DNA complex. In the tetramer, two primary dimers are arranged back to back
      with two oligonucleotides bound in clefts on opposite sides of the tetramer. The
      DNA molecules retain a B-type conformation and have an enclosed angle between
      their helical axes of 60 degrees. Sequence-specific interactions occur in both
      the major and minor grooves. Two Mg2+ ions are located close to the cleaved
      phosphate at the active site of NgoMIV. Biochemical experiments show that
      interactions between the recognition sites within the tetramer greatly increase
      DNA cleavage efficiency.

PMID- 10966653
TI  - Hot spots in beta-catenin for interactions with LEF-1, conductin and APC.
AB  - Interactions between beta-catenin and LEF-1/TCF, APC and conductin/axin are
      essential for wnt-controlled stabilization of beta-catenin and transcriptional
      activation. The wnt signal transduction pathway is important in both embryonic
      development and tumor progression. We identify here amino acid residues in beta
      catenin that distinctly affect its binding to LEF-1/TCF, APC and conductin. These
      residues form separate surface clusters, termed hot spots, along the armadillo
      superhelix of beta-catenin. We also show that complementary charged and
      hydrophobic amino acids are required for formation of the bipartite beta-catenin
      LEF-1 transcription factor. Moreover, we demonstrate that conductin/axin binding
      to beta-catenin is essential for beta-catenin degradation, and that APC acts as a
      cofactor of conductin/axin in this process. Binding of APC to conductin/axin
      activates the latter and occurs between their SAMP and RGS domains, respectively.

PMID- 10966654
TI  - Ternary complex between placental lactogen and the extracellular domain of the
      prolactin receptor.
AB  - The structure of the ternary complex between ovine placental lactogen (oPL) and
      the extracellular domain (ECD) of the rat prolactin receptor (rPRLR) reveals that
      two rPRLR ECDs bind to opposite sides of oPL with pseudo two-fold symmetry. The
      two oPL receptor binding sites differ significantly in their topography and
      electrostatic character. These binding interfaces also involve different hydrogen
      bonding and hydrophobic packing patterns compared to the structurally related
      human growth hormone (hGH)-receptor complexes. Additionally, the receptor
      receptor interactions are different from those of the hGH-receptor complex. The
      conformational adaptability of prolactin and growth hormone receptors is
      evidenced by the changes in local conformations of the receptor binding loops and
      more global changes induced by shifts in the angular relationships between the N-
      and C-terminal domains, which allow the receptor to bind to the two
      topographically distinct sites of oPL.

PMID- 10966655
TI  - Ask the doctor. I know that high triglyceride levels probably increase my risk
      for heart disease. My last blood tests showed that my cholesterol numbers were
      pretty good, but my triglycerides were 256 mg/dL. What should I do to bring that
      number down?

PMID- 10966656
TI  - By the way, doctor... No need to take Prilosec forever.

PMID- 10966657
TI  - What is recovery?

PMID- 10966658
TI  - In brief: new tool for digging Up cancer information

PMID- 10966659
TI  - By the way, doctor. This year, there's been alot of news about a cholesterol
      lowering drug that also reduces the risk of fractures. I am postmenopausal and
      would like to know whether I should be taking this drug.

PMID- 10966661
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 2: ethical aspects of CPR and ECC.

PMID- 10966662
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 3: adult basic life support. The American Heart Association in
      collaboration with the International Liaison Committee on Resuscitation.

PMID- 10966663
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 4: the automated external defibrillator: key link in the chain of
      survival. The American Heart Association in Collaboration with the International
      Liaison Committee on Resuscitation.

PMID- 10966664
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 5: new guidelines for first aid. The American Heart Association in
      collaboration with the International Liaison Committee on Resuscitation.

PMID- 10966665
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 1: Introduction to
      ACLS 2000: overview of recommended changes in ACLS from the guidelines 2000
      conference. The American Heart Association in collaboration with the
      International Liaison Committee on Resuscitation.

PMID- 10966666
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 2: defibrillation.
      The American Heart Association in collaboration with the International Liaison
      Committee on Resuscitation.

PMID- 10966667
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 3: adjuncts for
      oxygenation, ventilation and airway control. The American Heart Association in
      collaboration with the International Liaison Committee on Resuscitation.

PMID- 10966668
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 4: devices to assist
      circulation. The American Heart Association in collaboration with the
      International Liaison Committee on Resuscitation.

PMID- 10966669
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 5: pharmacology I:
      agents for arrhythmias. The American Heart Association in collaboration with the
      International Liaison Committee on Resuscitation.

PMID- 10966670
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 6: pharmacology II:
      agents to optimize cardiac output and blood pressure. The American Heart
      Association in collaboration with the International Liaison Committee on
      Resuscitation.

PMID- 10966671
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 7: algorithm approach
      to ACLS emergencies: section 7A: principles and practice of ACLS. The American
      Heart Association in collaboration with the International Liaison Committee on
      Resuscitation.

PMID- 10966672
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 6: advanced cardiovascular life support: section 8: postresuscitation
      care. The American Heart Association in collaboration with the International
      Liaison Committee on Resuscitation.

PMID- 10966674
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 7: the era of reperfusion: section 2: acute stroke. The American Heart
      Association in collaboration with the International Liaison Committee on
      Resuscitation.

PMID- 10966673
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 7: the era of reperfusion: section 1: acute coronary syndromes (acute
      myocardial infarction). The American Heart Association in collaboration with the
      International Liaison Committee on Resuscitation.

PMID- 10966675
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 8: advanced challenges in resuscitation: section 1: life-threatening
      electrolyte abnormalities. The American Heart Association in collaboration with
      the International Liaison Committee on Resuscitation.

PMID- 10966676
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 8: advanced challenges in resuscitation: section 2: toxicology in ECC.
      The American Heart Association in collaboration with the International Liaison
      Committee on Resuscitation.

PMID- 10966677
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 8: advanced challenges in resuscitation: section 3: special challenges
      in ECC. The American Heart Association in collaboration with the International
      Liaison Committee on Resuscitation.

PMID- 10966678
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 9: pediatric basic life support. The American Heart Association in
      collaboration with the International Liaison Committee on Resuscitation.

PMID- 10966679
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 10: pediatric advanced life support. The American Heart Association in
      collaboration with the International Liaison Committee on Resuscitation.

PMID- 10966680
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 11: neonatal resuscitation. The American Heart Association in
      collaboration with the International Liaison Committee on Resuscitation.

PMID- 10966681
TI  - Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care. Part 12: from science to survival: strengthening the chain of survival in
      every community. The American Heart Association in collaboration with the
      International Liaison Committee on Resuscitation.

PMID- 10966682
TI  - The most important changes in the international ECC and CPR guidelines 2000.

PMID- 10966683
TI  - Guidelines based on fear of type II (false-negative) errors : why we dropped the
      pulse check for lay rescuers.

PMID- 10966685
TI  - Diagnosis Please Certificate of Recognition Awarded to Seyed Alireza Emamian, MD,
      PhD.

PMID- 10966684
TI  - Guidelines based on the principle "first, do no harm" : new guidelines on
      tracheal tube confirmation and prevention of dislodgment.

PMID- 10966686
TI  - Impact of managed care on scholarly activity and patient care: case study of 12
      academic radiology and radiation oncology departments.
AB  - Six departments of radiology and six departments of radiation oncology from areas
      with low, medium, or high managed care penetration were asked to complete a
      questionnaire designed to address the impact of managed care on research and
      scholarly activity. Information, when available, was taken from fiscal years 1993
      and 1998. Questionnaires were followed by site visits to the 12 departments. The
      study showed that departments with medium to high managed care penetration
      reported more dissatisfaction in their ability to remain active in their
      education and research goals. Results indicated that for the period surveyed, the
      departments needed to increase clinical time to make up for decreasing patient
      care revenues. In turn, this has reduced the time and money devoted to scholarly
      activities. Information from this study will be used to develop a trends database
      for all U.S. radiology and radiation oncology departments. This, together with a
      more comprehensive study by the RSNA, will assist in measuring the current and
      potential long-term impact of managed care and other system changes on the
      practice of radiology and radiation oncology.

PMID- 10966687
TI  - Rings, slings, and other things: vascular compression of the infant trachea
      updated from the midcentury to the millennium--the legacy of Robert E. Gross, MD,
      and Edward B. D. Neuhauser, MD.
AB  - In the first half of the 20th century, pediatric chest imaging was limited mainly
      to the performance of conventional radiography, including barium esophagography
      and occasionally bronchography and angiography. Despite this limited imaging
      approach, by 1950 the diagnosis and treatment of vascular "rings" compressing
      infant airways had been accomplished with the pioneering efforts of Robert E.
      Gross, MD, in the field of surgery, and Edward B. D. Neuhauser, MD, in the field
      of radiology. The next two decades brought the recognition of pulmonary arterial
      "sling," or anomalous left pulmonary artery, in diagnosis and treatment.
      Recognition of still another vascular compressive syndrome in infants was
      identified as that due to the absence of the pulmonary valve. These "rings,
      slings, and other things" are now evaluated with magnetic resonance (MR) imaging,
      including MR angiography, and computed tomography (CT), including CT angiography,
      with the added use of three-dimensional reconstruction. These are the legacies of
      Drs Gross and Neuhauser.

PMID- 10966688
TI  - Sedation in MR imaging: what price safety?

PMID- 10966689
TI  - Occipital condylar fractures: a review.
AB  - The purpose of this review article is to summarize the epidemiology, pertinent
      anatomy, mechanisms of injury, and classification systems of occipital condylar
      fractures (OCFs), as well as their clinical presentation and screening, the
      importance of computed tomography (CT) for detection, and current treatment
      options. The authors emphasize the rate of occurrence of OCFs, which may be
      detected in as many as 16% of patients with craniocervical injury. Clinical
      presentation is not specific, and OCF is not readily diagnosed at physical
      examination. Failure to diagnose may result in substantial morbidity, and thus
      accurate diagnosis is mandatory for both therapeutic and medicolegal
      implications. The diagnosis is most likely to be made with CT. Thin-section CT
      technique is the method of choice to evaluate the traumatized craniocervical
      junction. OCFs should be suspected in all patients sustaining high-energy blunt
      trauma to the head and/or upper cervical spine, resulting from axial loading,
      lateral bending and/or rotation, and/or direct blow. Besides a CT study assessing
      potential intracranial injuries, these patients require CT of the craniocervical
      junction. Radiologists should be aware of the types of OCFs and associated
      injuries.

PMID- 10966690
TI  - Sedation procedures in MR imaging: safety, effectiveness, and nursing effect on
      examinations.
AB  - PURPOSE: To measure the safety and effectiveness of conscious sedation in order
      to assess utilization and the effect on magnetic resonance (MR) imaging
      examinations. MATERIALS AND METHODS: A database of conscious sedation records for
      MR imaging at the Johns Hopkins Hospital, Baltimore, Md, from 1991 to 1998 was
      searched. Safety data according to medication and procedure duration for each
      nurse were tabulated for 6,093 patient records. Data were analyzed by using
      quality control statistical measures to determine time utilization and
      effectiveness. Break-even costs for the procedure were determined. RESULTS: Of
      6,093 patients scheduled for examination, 4,761 patients (78.1%) received
      conscious sedation by the MR conscious sedation service. Complications were
      observed in 20 of the 4,761 patients (0.42%). No deaths occurred. The most common
      complication was oxygen desaturation (n = 8). Diagnostic and complete MR
      examinations were performed in 4,453 of the 4,761 patients (93.5%). The mean time
      to sedate the patient (+/- SD) was 23.6 minutes +/- 15.2 for specialized MR
      sedation nurses and 26.8 minutes +/- 20.1 for general radiology nurses (P:
      <.001). For inpatient nurses from the inpatient hospital units, the sedation time
      was considerably longer (47.3 minutes +/- 36.6, P: <.001) and more variable.
      Break-even costs were 37% ($11 vs $8 for MR room time) more for general radiology
      nurses than for specialized MR sedation nurses performing the procedure.
      CONCLUSION: Conscious sedation is safe and has a high effectiveness rate. A
      highly specialized nursing staff reduces procedure variability and cost.

PMID- 10966691
TI  - Sedation and analgesia in adult patients: evaluation of a staged-dose system
      based on body weight for use in abdominal interventional radiology.
AB  - PURPOSE: To evaluate the safety and effectiveness of a systematic protocol for
      sedation and analgesia in interventional radiology. MATERIALS AND METHODS: Ninety
      one adult patients underwent 113 abdominal interventional procedures. Fentanyl
      citrate and midazolam hydrochloride were administered in one to five steps (A, B,
      C, D, E) until the patient was drowsy and tranquil at the effective loading dose
      (ELD). Doses per step were as follows: A, fentanyl 1 microg per kilogram of body
      weight; B, midazolam 0.010-0.035 mg/kg; C, repeat dose in A; D, repeat half the
      dose in B; and E, midazolam 1-2-mg boluses (maximum, 0.15 mg/kg). RESULTS: The
      ELD was reached in no procedure after step A, in 70 after B, in 23 after C, and
      in 18 after D. Step E was needed in two procedures. The mean maximum pain score
      (scale of 0 to 10) was 3.4; pain scores in 85 (75%) procedures were 4 or less
      (discomforting). Severe pain occurred in seven (6%) procedures. Hypoxia (oxygen
      saturation < 90%) occurred in 11 (22%) procedures performed in patients breathing
      room air and four (6%) performed in those breathing supplemental oxygen (P:
      =.04). All patients responded to supplemental oxygen. CONCLUSION: This stepwise
      "ABCDE protocol" allows safe and effective sedation of patients. It is easy to
      use and may be useful in training radiology residents, staff, and nurses in the
      techniques of sedation and analgesia. Supplemental oxygen should be used
      routinely.

PMID- 10966692
TI  - Conscious sedation and analgesia for routine aortofemoral arteriography: a
      prospective evaluation.
AB  - PURPOSE: To compare the effectiveness of temazepam and midazolam hydrochloride
      with or without fentanyl citrate versus a placebo in promoting patient acceptance
      of diagnostic aortofemoral arteriography. MATERIALS AND METHODS: One hundred
      twenty-five patients undergoing aortofemoral arteriography were prospectively and
      randomly assigned to one of four treatment arms: placebo (group A), oral
      temazepam (group B), intravenous midazolam (group C), or intravenous midazolam
      and fentanyl (group D). Patients were blinded to the administered sedative. Five
      point scales were used to assess degree of patient discomfort, willingness to
      undergo the same procedure again, patient compliance, and preprocedural anxiety.
      RESULTS: There was no difference between patient groups in willingness to return
      for a repeat procedure (P: =.89). Group C patients were less compliant during the
      procedure (P: =.034). Mean patient discomfort scores were 1.81 for group A, 1.84
      for group B, 1. 53 for group C, and 1.27 for group D. Discomfort experienced
      during the procedure was not related to the degree of preprocedural anxiety (P:
      =.42). Patients who had previously undergone arteriography reported a higher
      level of pain than did those who had not (P: =. 021). CONCLUSION: Most patients
      experienced only low-level discomfort during diagnostic aortofemoral
      arteriography. In the authors' opinion, conscious sedation should only be used
      selectively, not routinely, for diagnostic aortofemoral arteriography.

PMID- 10966693
TI  - Sialolithiasis: MR sialography of the submandibular duct--an alternative to
      conventional sialography and US?
AB  - PURPOSE: To determine the value of magnetic resonance (MR) sialography for the
      diagnosis of sialolithiasis by comparing results prospectively with those of
      ultrasonography (US) and digital sialography. MATERIALS AND METHODS: MR
      sialography was prospectively performed with T2-weighted three-dimensional (3D)
      constructive interference in steady-state (CISS) and rapid acquisition with
      relaxation-enhancement (RARE) sequences in 24 patients suspected of having
      sialolithiasis. Evoked salivation was used as contrast material. T1-weighted spin
      echo and T2-weighted turbo spin-echo MR imaging also were performed. The results
      were then compared with those of US and digital sialography, with the latter as
      standard of reference. RESULTS: The 3D CISS images were significantly (P: <.05)
      superior to RARE images for demonstrating the submandibular ductal system,
      followed by T2-weighted turbo spin-echo images (P: <.01) and T1-weighted spin
      echo images (P: <.001). The sensitivity and specificity were 100% and 80%,
      respectively, for CISS MR sialography and 80% and 100%, respectively, for RARE MR
      imaging. The sensitivity and specificity of US were both 80%. CONCLUSION: MR
      sialography with evoked salivation is noninvasive and allows delineation of the
      submandibular ductal system and detection of sialoliths with accuracy that is
      similar to that of digital sialography and superior to that of US.

PMID- 10966694
TI  - Normal brain development and aging: quantitative analysis at in vivo MR imaging
      in healthy volunteers.
AB  - PURPOSE: To quantitate neuroanatomic parameters in healthy volunteers and to
      compare the values with normative values from postmortem studies. MATERIALS AND
      METHODS: Magnetic resonance (MR) images of 116 volunteers aged 19 months to 80
      years were analyzed with semiautomated procedures validated by means of
      comparison with manual tracings. Volumes measured included intracranial space,
      whole brain, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF).
      Results were compared with values from previous postmortem studies. RESULTS:
      Whole brain and intracranial space grew by 25%-27% between early childhood (mean
      age, 26 months; age range, 19-33 months) and adolescence (mean age, 14 years; age
      range, 12-15 years); thereafter, whole-brain volume decreased such that
      volunteers (age range, 71-80 years) had volumes similar to those of young
      children. GM increased 13% from early to later (6-9 years) childhood. Thereafter,
      GM increased more slowly and reached a plateau in the 4th decade; it decreased by
      13% in the oldest volunteers. The GM-WM ratio decreased exponentially from early
      childhood through the 4th decade; thereafter, it gradually declined. In vivo
      patterns of change in the intracranial space, whole brain, and GM-WM ratio agreed
      with published postmortem data. CONCLUSION: MR images accurately depict normal
      patterns of age-related change in intracranial space, whole brain, GM, WM, and
      CSF. These quantitative MR imaging data can be used in research studies and
      clinical settings for the detection of abnormalities in fundamental neuroanatomic
      parameters.

PMID- 10966695
TI  - MR imaging and (1)H spectroscopy of brain metabolites in hepatic encephalopathy:
      time-course of renormalization after liver transplantation.
AB  - PURPOSE: To evaluate changes in hydrogen 1 magnetic resonance (MR) spectroscopic
      findings in overt or subclinical hepatic encephalopathy (HE) after liver
      transplantation and to compare these changes with clinical outcomes and basal
      ganglia high signal intensity (BGH). MATERIALS AND METHODS: Twenty-two patients
      scheduled for liver transplantation and 17 healthy control subjects were examined
      with (1)H MR spectroscopy and standard nonenhanced MR imaging. Eight patients
      underwent complete MR imaging and (1)H spectroscopic examinations before liver
      transplantation and at 3-4-week, 12-28-week, and 10-12-month follow-up after
      liver transplantation. RESULTS: Before liver transplantation, typical (1)H
      spectroscopic changes-decreased myo-inositol (mI)/creatine (Cr) and choline
      (Cho)/Cr ratios and an elevated glutamine and glutamate (Glx)/Cr ratio-were found
      in 21 patients. Eighteen patients had BGH at T1-weighted imaging. Three to 7
      months after liver transplantation, the mI/Cr and Glx/Cr ratios were within the
      normal range in five of eight and eight of eight patients, respectively, without
      any residual signs of subclinical or overt HE; however, at MR imaging, seven
      patients still had BGH. CONCLUSION: After successful liver transplantation,
      renormalization of HE-specific brain metabolite changes is detected at (1)H
      spectroscopy and precedes the disappearance of BGH. The neuropsychologic signs of
      subclinical or overt HE follow the changes seen at (1)H spectroscopy rather than
      those seen at MR imaging.

PMID- 10966696
TI  - Hepatic cavernous hemangioma: temporal peritumoral enhancement during multiphase
      dynamic MR imaging.
AB  - PURPOSE: To determine whether temporal parenchymal enhancement around hepatic
      cavernous hemangiomas can be correlated with the rapidity of intratumoral
      contrast material enhancement and/or tumor volume at dynamic magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Dynamic MR images obtained in 94 patients
      with 167 hemangiomas were retrospectively reviewed for peritumoral enhancement.
      Tumor volume was estimated by using the longest dimension on nonenhanced images.
      Speed of intratumoral contrast material enhancement was determined with early
      nonequilibrium phase images and was categorized as rapid (>75% of tumor volume),
      intermediate (25%-75% of tumor volume), or slow (<25% of tumor volume). RESULTS:
      Thirty-two of the 167 hemangiomas (19%) had temporal peritumoral enhancement,
      which was more common in hemangiomas with rapid enhancement (20 of 49 [41%]) than
      in those with intermediate (12 of 62 [19%]) and slow (0 of 56 [0%]) enhancement
      (P: <.001). The mean diameter of the hemangiomas with peritumoral enhancement was
      not significantly different from that of hemangiomas without peritumoral
      enhancement (P: >.05). Hemangiomas with rapid enhancement (mean diameter, 16 mm
      +/- 8), however, were significantly smaller than those with intermediate
      enhancement (mean diameter, 33 mm +/- 34) (P: <.001). CONCLUSION: Temporal
      peritumoral enhancement on dynamic MR images of hepatic hemangiomas correlates
      well with the speed of intratumoral contrast material enhancement and was most
      commonly encountered in rapidly enhancing small lesions. There was no
      statistically significant relationship, however, between peritumoral enhancement
      and tumor volume.

PMID- 10966697
TI  - Extrahepatic metastases of hepatocellular carcinoma.
AB  - PURPOSE: To determine the relative frequency, incidence, and locations of
      metastases of hepatocellular carcinoma (HCC), correlate extrahepatic metastatic
      disease with intrahepatic tumor staging, and determine the computed tomographic
      (CT) manifestations of HCC metastases. MATERIALS AND METHODS: CT findings in 403
      consecutive patients with HCC at our institution since 1992 were reviewed
      retrospectively. One hundred forty-eight patients with extrahepatic metastatic
      HCC were identified, and the locations, sizes, and attenuation and enhancement
      characteristics of the lesions were recorded. RESULTS: A majority (128 [86%] of
      148) of patients with extrahepatic HCC foci had either intrahepatic stage IVA
      tumor (112 [76%] patients) or an intrahepatic stage III tumor (16 [11%] patients)
      at the occurrence of metastases. The most frequent site of the first detectable
      metastasis was the lung (58 [39%] patients). Tabulation of all extrahepatic
      metastatic sites showed the most common to be the lung in 81 (55%) patients, the
      abdominal lymph nodes in 60 (41%) patients, and the bone in 41 (28%) patients.
      CONCLUSION: The lung, abdominal lymph nodes, and bone are the most common sites
      of extrahepatic metastatic HCC. Most extrahepatic HCC occurs in patients with
      advanced intrahepatic tumor stage (stage IVA). Incidental extrahepatic lesions at
      CT in patients with stage I or II intrahepatic HCC are unlikely to represent
      metastatic HCC.

PMID- 10966699
TI  - Segmental wall thickening in the colonic loop distal to colonic carcinoma at CT:
      importance and histopathologic correlation.
AB  - PURPOSE: To determine the importance of the finding of segmental wall thickening
      in the colonic loop distal to colonic carcinoma at computed tomography (CT) by
      means of histopathologic correlation. MATERIALS AND METHODS: Thirteen consecutive
      patients whose helical CT scans showed segmental wall thickening (>1 cm in
      maximal width, >5 cm in length) in the colonic loop distal to colonic carcinoma
      were included. The thickness and length of an involved segment, location,
      morphologic tumor type, CT patterns of wall thickening, and pericolic changes
      were evaluated. Surgical pathologic findings in all 13 patients were correlated
      with CT findings. RESULTS: The involved segment distal to the colonic carcinoma
      showed circumferential wall thickening with a preserved wall layer pattern at CT.
      Pericolic changes of varying degrees were seen in 10 patients. Histopathologic
      examination revealed submucosal and subserosal edema (n = 6), chronic
      inflammation and fibrosis (n = 5), or both (n = 1), and no histopathologic
      alteration (n = 1). The tumors were mostly fungating (n = 11), larger than 5 cm
      in the greatest dimension (n = 12), located in the ascending colon (n = 10), and
      extended to pericolic adipose tissue (n = 11). CONCLUSION: Colonic carcinoma,
      especially a large fungating type involving the ascending colon with pericolic
      infiltration, can produce segmental wall thickening in the distal segment at CT,
      which represents edema or colitis at histopathologic examination.

PMID- 10966698
TI  - Optimization of CT colonography technique: prospective trial in 180 patients.
AB  - PURPOSE: To assess the added benefits of prone positioning in addition to supine
      positioning and oral iodinated contrast medium for help in the detection of
      colonic polyps at computed tomographic (CT) colonography. MATERIALS AND METHODS:
      CT colonography was performed in prone and supine positions in 180 patients with
      polyps or risk factors for colonic neoplasia. Patients were randomly assigned to
      receive a standard bowel preparation or a standard preparation plus oral
      iodinated contrast medium. One radiologist interpreted supine images alone, and
      another analyzed supine and prone images. All patients subsequently underwent
      colonoscopy. RESULTS: At colonoscopy, 121 large (> or =1-cm-diameter) polyps and
      142 smaller (0.5-0.9-cm) polyps were identified. Prone positioning resulted in
      increased sensitivity for identification of patients with large (> or =1-cm)
      polyps (increase from 70% to 85%, P: =.004) and of patients with polyps 0.5 cm or
      larger (increase from 75% to 88%, P: <.005), with no change in specificity. Use
      of oral contrast medium did not significantly improve polyp detection even in the
      subset of patients in whom colonic fluid attenuation was markedly increased.
      CONCLUSION: Acquisition and review of supine and prone CT colonographic images
      significantly improves the ability to identify patients with polyps 0.5 cm in
      diameter or larger. Administration of oral iodinated contrast medium does not
      significantly improve polyp detection.

PMID- 10966700
TI  - Abdominal helical CT: evaluation of optimal doses of intravenous contrast
      material--a prospective randomized study.
AB  - PURPOSE: To determine the optimal dose of intravenous contrast material for
      helical computed tomography (CT) of the abdomen on the basis of patient weight.
      MATERIALS AND METHODS: A prospective randomized study of helical CT of the
      abdomen was performed by using different doses of intravenous contrast material
      in 221 patients (mean body weight, 57.3 kg) who were assigned randomly to three
      groups receiving 1.5, 2.0, or 2.5 mL/kg or a fixed dose of 100 mL of iopamidol
      300. The degree of enhancement was scored visually. The CT numbers (HU) of the
      aorta, portal vein, liver, and pancreas were obtained at three levels of the
      abdomen. RESULTS: In arterial enhancement, the 2.0 mL/kg, 2.5 mL/kg, and fixed
      dose groups were significantly better than the 1.5 mL/kg group, but there was no
      significant difference among the 2.0 mL/kg, 2.5 mL/kg, or fixed-dose groups. The
      degree of enhancement of the liver, pancreas, and portal vein increased with
      larger doses. At visual analysis, hepatic parenchymal enhancement was graded as
      good or excellent in 64% of the 1.5 mL/kg, 85% of the 2.0 mL/kg, 94% of the 2.5
      mL/kg, and 65% of the fixed-dose groups. CONCLUSION: When dose was tailored to
      patient weight, the use of 2.0-2.5 mL/kg of intravenous contrast material
      produced better results than did 1.5 mL/kg or a fixed dose. Arterial enhancement
      did not differ among the 2.0 mL/kg, 2.5 mL/kg, or fixed-dose groups.

PMID- 10966701
TI  - Case 30.

PMID- 10966702
TI  - Case 26: Jejunojejunal intussusception secondary to a lipoma.

PMID- 10966703
TI  - Renal growth in children with severe vesicoureteral reflux: 10-year prospective
      study of medical and surgical treatment: the International Reflux Study in
      Children (European branch).
AB  - PURPOSE: To determine whether medical or surgical treatment better promotes renal
      growth in children with severe vesicoureteric reflux (VUR) and to examine factors
      influencing renal growth. MATERIALS AND METHODS: Three hundred two children
      younger than 11 years with urinary tract infection and grade III or IV VUR were
      randomly assigned to surgical (n = 149) or medical (n = 153) treatment and were
      followed up at serial intravenous urography for up to 5 years; 223, for up to 10
      years (surgical, n = 110; medical, n = 113). Renal size was measured
      planimetrically on serial intravenous urograms and was related to the virtual
      height of L1 through L3 by expressing it as an SD score. RESULTS: There was no
      significant difference in mean renal growth between patients treated surgically
      or those treated medically after 5- or 10-year follow-up. Bilateral renal size of
      80 surgical and 75 medical patients remained within 1 SD score. In patients
      entering the study at 2 years of age or younger and in those with grade IV VUR,
      bilateral VUR, or renal scars, there was a trend toward improved renal growth in
      those treated medically, but this finding was not statistically significant. When
      renal scarring or thin parenchyma was unilateral, the affected kidney grew less
      well, irrespective of treatment. Bilateral renal scarring was usually
      asymmetrical, with a corresponding effect on renal growth. CONCLUSION: There was
      no significant difference in renal growth during 10 years between surgical and
      medical treatment in patients with severe reflux.

PMID- 10966704
TI  - Arterioportal fistulas in patients with liver cirrhosis: usefulness of color
      Doppler US for screening.
AB  - PURPOSE: To evaluate the usefulness of routine ultrasonographic (US) evaluation
      of the hepatic arterial resistive and pulsatility indexes and of the direction of
      portal venous blood flow for the diagnosis of intrahepatic arterioportal fistulas
      (APFs) in patients with liver cirrhosis. MATERIALS AND METHODS: In all patients
      with cirrhosis examined at one center over 4 years, the resistive (RI) and the
      pulsatility (PI) indexes in the right and left branches of the hepatic artery
      were evaluated with Doppler US. An APF was suspected when an RI decrease of at
      least 20% and a PI decrease of at least 30% were present in one hepatic lobe
      relative to values in the other lobe and portal blood flow in the lobe with the
      decreased values was reversed. The RI and PI in patients with an APF were
      compared with those in 75 patients with cirrhosis and without APFs at
      angiography. RESULTS: Seven patients with an APF were identified. APFs suspected
      at Doppler US were always confirmed with angiography. The percent differences +/-
      SD in the RI and the PI between the two intrahepatic branches of the hepatic
      artery in patients with versus in patients without an APF were as follows: RI,
      35% +/- 6 (range, 27%-42%) versus 5% +/- 4 (range, 0%-15%) (P: <.001); PI, 50% +/
      5 (range, 41%-58%) versus 11% +/- 7 (range, 0%-26%) (P: <.001). CONCLUSION: The
      intrahepatic arterial resistive and pulsatility indexes and the direction of
      portal blood flow should be evaluated in routine screening for APFs in patients
      with liver cirrhosis.

PMID- 10966705
TI  - Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary
      Angiography-Indirect CT Venography Cooperative Group.
AB  - PURPOSE: To assess the clinical benefits of performing indirect computed
      tomographic (CT) venography after pulmonary CT angiography to detect deep venous
      thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS
      AND METHODS: The authors prospectively enrolled 541 consecutive patients who
      underwent pulmonary CT angiography for suspected pulmonary embolism at seven
      institutions. Using a protocol that optimizes venous enhancement without
      additional contrast material injection, the authors obtained contiguous images
      from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed
      in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and
      pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541
      patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no
      pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of
      thromboembolic disease by 18%. Among 116 patients who underwent US and indirect
      CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT
      venography. In four additional cases, DVT was seen at only indirect CT
      venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a
      substantial number had DVT in the absence of pulmonary embolism. Combined
      pulmonary CT angiography-indirect CT venography can depict these cases with
      accuracy comparable to that of US and thus could have a significant effect on
      patient care.

PMID- 10966706
TI  - Vena cavography with CO(2) versus with iodinated contrast material for inferior
      vena cava filter placement: a prospective evaluation.
AB  - PURPOSE: To determine whether carbon dioxide (CO(2)) vena cavography can safely
      guide the placement of inferior vena cava (IVC) filters. MATERIALS AND METHODS:
      One hundred nineteen patients were prospectively enrolled in this study. CO(2
      )cavograms were obtained and evaluated for IVC diameter, location of renal veins,
      and presence of thrombus and venous anomalies. If CO(2 )cavography was judged to
      be adequate, an IVC filter was deployed. After filter placement, cavography was
      performed with iodinated contrast material; these images were compared with the
      CO(2) cavograms. RESULTS: Two patients experienced mild side effects related to
      venous CO(2) injection. Comparison of cavograms obtained with CO(2) and iodinated
      contrast-enhanced material showed the caval size to be within 3 mm in all 119
      patients. In 116 patients (97.5%), CO(2) cavography was judged to be adequate,
      and in 115 patients, filters were placed. In three (2.5%) patients, it was
      necessary to perform iodinated contrast-enhanced cavography before filter
      deployment. All six cases of venous anomaly and 11 (78.6%) of 14 cases of
      thrombosis were clearly identified with CO(2) cavography. One filter was
      maldeployed owing to misinterpretation of the CO(2) cavogram. CONCLUSION: CO(2)
      cavography is well tolerated, safe, and adequate for identification of the
      parameters necessary for filter deployment. It is especially valuable in patients
      with a history of reaction to iodinated contrast material or renal insufficiency.

PMID- 10966707
TI  - Malignant gastroduodenal obstructions: treatment by means of a covered expandable
      metallic stent-initial experience.
AB  - PURPOSE: To investigate the technical feasibility and clinical effectiveness of a
      polyurethane-covered expandable nitinol stent in the treatment of malignant
      gastroduodenal obstructions. MATERIALS AND METHODS: The stent was constructed in
      house by weaving a single thread of 0.2-mm nitinol wire in a tubular
      configuration and was covered with polyurethane solution by means of a dipping
      method. With fluoroscopic guidance, the stent was placed in 19 consecutive
      patients with malignant gastric outlet obstruction (n = 15) or duodenal
      obstruction (n = 4). All patients had severe nausea and recurrent vomiting, and
      their obstructions were inoperable. RESULTS: Stent placement was technically
      successful in all but one patient. After stent placement, symptoms improved in
      all but one patient, who had another stenosis at the proximal jejunum. One
      patient with stent placement in the second portion of the duodenum became
      jaundiced. During the mean follow-up of 11 weeks, stent migration occurred in
      five patients 1-4 days after the procedure. All patients with stent migration
      were treated by means of placing a second, uncovered nitinol stent. Two of these
      five patients showed recurrence of stricture because of tumor ingrowth; they
      underwent coaxial placement of a third, covered nitinol stent with good results.
      CONCLUSION: Placement of a polyurethane-covered expandable nitinol stent seems to
      be technically feasible and effective for palliative treatment of inoperable
      malignant gastroduodenal obstructions. Stent migration, however, is problematic
      and requires further investigation.

PMID- 10966708
TI  - Mediastinal lymphadenopathy: diagnostic yield of transbronchial mediastinal lymph
      node biopsy with CT fluoroscopic guidance-initial experience.
AB  - PURPOSE: To determine whether the use of computed tomographic (CT) fluoroscopy to
      guide transbronchial needle aspiration (TBNA) of mediastinal lymph nodes can
      improve the diagnostic yield. MATERIALS AND METHODS: CT fluoroscopy was used to
      guide TBNA in 12 consecutive patients with mediastinal lymphadenopathy who had
      previously undergone nondiagnostic conventional TBNA. CT fluoroscopy was used to
      confirm the location of the biopsy needle by using a "quick-check" technique (ie,
      fluoroscopy was performed sparingly after needle insertion). The location of each
      needle, the total procedural and fluoroscopic times, and any complications were
      recorded. RESULTS: All CT fluoroscopic procedures were performed in less than 1
      hour, and a tissue diagnosis was established in all patients. Eighteen lymph
      nodes with a diameter of 0.8-2.4 cm were sampled with 116 needle passes. CT
      fluoroscopy documented inadequate positioning in 48 of the 116 (41.3%) needle
      passes. Eighteen (15.5%) needles did not fully penetrate the tracheobronchial
      tree. Six needles (5.2%) were placed into the great vessels. Malignant disease
      was diagnosed in nine patients, and benign disease was diagnosed in three. The
      mean fluoroscopic exposure time was 20.5 seconds +/- 12.7. No pneumothoraces or
      substantial hemorrhage were observed. CONCLUSION: CT fluoroscopic guidance for
      TBNA procedures is a safe and efficient means of providing diagnostic material
      and should be considered for patients who have previously undergone nondiagnostic
      blinded TBNA.

PMID- 10966709
TI  - Evaluation of air trapping at CT: comparison of continuous-versus suspended
      expiration CT techniques.
AB  - PURPOSE: To compare thin-section computed tomographic (CT) scans obtained during
      suspended end expiration with helical CT scans obtained during continuous
      expiration for the assessment of air trapping. MATERIALS AND METHODS: Forty-nine
      patients with an airway disease were examined with suspended-end-expiration CT
      after a 6-8-second expiratory maneuver, which was followed with continuous
      expiration CT during a 10-second expiratory maneuver. The extent of expiratory
      air-trapping areas was calculated by two observers by using a semiquantitative
      grid score. The relative decrease in attenuation in the areas of air trapping was
      evaluated with a visual continuous-scale score. RESULTS: Air trapping was noted
      in 36 and 35 patients with continuous-expiration CT and with suspended-end
      inspiration CT, respectively. The extents of and relative attenuation decreases
      in air-trapping areas in patients with air-trapping areas on at least one
      expiratory CT scan increased significantly in scans obtained with continuous
      expiration CT compared with those obtained with suspended-end-expiration CT,
      respectively, with mean extent scores of 0.24 +/- 0.20 (SD) and 0.18 +/- 0.20
      (paired t test, P: =.001) respectively, and with mean relative contrast decrease
      scores of 0.35 +/- 0.23 and 0.27 +/- 0.23 (paired t test, P: =.007),
      respectively. CONCLUSION: When suspended-end-expiration CT images are ambiguous,
      complementary continuous-expiration CT can be used to improve the conspicuity and
      apparent extent of air trapping.

PMID- 10966710
TI  - Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111
      patients.
AB  - PURPOSE: To determine whether various eosinophilic lung diseases can be
      differentiated by means of thin-section computed tomography (CT). MATERIALS AND
      METHODS: Thin-section CT scans in 111 patients with eosinophilic lung diseases-40
      with chronic eosinophilic pneumonia, 16 with Churg-Strauss syndrome, 16 with
      allergic bronchopulmonary aspergillosis (ABPA), 13 with acute eosinophilic
      pneumonia, 12 with simple pulmonary eosinophilia, 11 with drug-induced
      eosinophilic pneumonia, and three with hypereosinophilic syndrome-were assessed
      independently by two observers. The observers recorded the abnormalities,
      diagnosis, and degree of confidence in the diagnosis. RESULTS: The two observers
      made a correct first-choice diagnosis on average in 61% of readings. The correct
      diagnosis was made in 78% of cases of chronic eosinophilic pneumonia; 81%, acute
      eosinophilic pneumonia; 44%, Churg-Strauss syndrome; 84%, ABPA; 17%, simple
      pulmonary eosinophilia; 27%, drug-induced eosinophilic pneumonia; and 33%,
      hypereosinophilic syndrome. The two observers made a correct diagnosis with a
      high degree of confidence in 36% of readings. There was moderate agreement
      between the observers for the correct diagnosis (kappa, 0.47) and for the correct
      diagnosis with a high degree of confidence (kappa, 0.59). CONCLUSION: Although
      eosinophilic lung diseases often can be differentiated by means of thin-section
      CT, correlation between CT findings and careful clinical evaluation are required
      for a definitive diagnosis.

PMID- 10966711
TI  - Coronary arterial stents: safety and artifacts during MR imaging.
AB  - PURPOSE: To investigate the safety and imaging artifacts with different coronary
      arterial stents and magnetic resonance (MR) imaging sequences. MATERIALS AND
      METHODS: The heating, artifacts, and ferromagnetism with different stents were
      studied with a 1.5-T MR tomograph with ultrafast gradients by using turbo spin
      echo, turbo gradient-echo, and echo-planar imaging sequences. Nineteen stents,
      which were 8-25 mm in length and 3.0-4.5 mm in diameter, were evaluated. Stent
      deviation induced by the magnetic field and during MR imaging, migration, and
      heating caused by the radio-frequency pulses were examined. The size of imaging
      artifacts was measured with all the stents under standardized conditions and with
      six stents after their implantation into the coronary arteries of freshly
      explanted pig hearts. RESULTS: All except two types of stents showed minimal
      ferromagnetism. No device migration or heating was induced. Turbo spin-echo
      images had minimal artifacts; larger artifacts were seen on the turbo gradient
      echo and echo-planar images. With ultrafast gradients, the artifacts on the echo
      planar images were substantially reduced. CONCLUSION: The studied coronary stents
      were not influenced by heating or motion during 1.5-T MR imaging. Artifact size
      differed according to the type and size of the stent and the MR imaging sequence
      used. Thus, patients with these stents can be safely examined.

PMID- 10966712
TI  - Comparison of US utilization and technical costs before and after establishment
      of 24-hour in-house coverage for US examinations.
AB  - PURPOSE: To compare data regarding the cost and number of ultrasonographic (US)
      examinations performed for 6 months, before and after institution of 24-hour in
      house sonographer coverage. MATERIALS AND METHODS: Data for a 6-month period
      during which US services were provided by a sonographer on call from 11 PM to 7
      AM were compared with data for a 6-month period during which a sonographer was in
      house during this shift. RESULTS: With 11 PM to 7 AM on-call coverage, the
      sonographers performed 147 examinations in a 6-month period, an average of 0.81
      examination per shift. After institution of in-house coverage for this shift, 792
      US examinations were performed in 6 months, an average of 4.3 examinations per
      shift. The cost for 11 PM to 7 AM in-house sonographer coverage for 6 months was
      approximately $16,000 more than that for on-call coverage. This cost would be
      offset by revenues from one additional examination per night. The cost per
      examination for the 11 PM to 7 AM shift decreased from $124.70 to $43.33.
      CONCLUSION: At the authors' institution, 24-hour in-house sonographer coverage
      resulted in additional cost, which was offset by revenues from additional
      examinations. There was nearly a fivefold increase in the number of US
      examinations performed per shift. These examinations were performed more
      expediently, enabling more rapid patient triage.

PMID- 10966713
TI  - Renal cysts: is attenuation artifactually increased on contrast-enhanced CT
      images?
AB  - PURPOSE: To determine if the attenuation values of simple renal cysts are
      artifactually increased on contrast material-enhanced, clinically acquired spiral
      computed tomographic (CT) images. MATERIALS AND METHODS: Dual-phase renal spiral
      CT studies (5-mm collimation; pitch, 1.0) were retrospectively analyzed in 24
      consecutive patients who had ultrasonographic (US) documentation of simple renal
      cysts. Forty-eight cysts were identified. The attenuation values of each cyst
      were measured on nonenhanced, cortical phase, and nephrographic phase images. The
      size and the location of each cyst in relation to the renal parenchyma were also
      recorded. RESULTS: The cysts were 0.6-10.8 cm in diameter (mean, 2.6 cm; SD,
      2.0). The mean attenuation change in the cysts from nonenhanced to contrast
      enhanced images was statistically significant in a comparison of cortical phase
      and nephrographic phase images (P: <.01): +1.8 HU (SD, 3.8) for cortical phase
      and +3. 6 HU (SD, 5.6) for nephrographic phase images. Renal cysts 1.0 cm or
      smaller showed a higher attenuation increase (mean, +4.0 HU for cortical phase
      and +11.0 HU for nephrographic phase). None of the renal cysts larger than 1.0 cm
      demonstrated an increase greater than 10 HU (mean, +1.4 HU for cortical phase and
      +2.3 HU for nephrographic phase). Intraparenchymal cysts showed higher mean
      attenuation changes than the exophytic cysts. CONCLUSION: Attenuation values in
      the renal cysts increased artifactually on contrast-enhanced images, but this
      pseudoenhancement was not substantial and was less than 10 HU when the cyst was
      larger than 1. 0 cm in diameter.

PMID- 10966714
TI  - Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon
      cause of primary adrenal hypercortisolism.
AB  - PURPOSE: To describe the imaging findings in the adrenal glands of 12 patients
      with adrenocorticotropin (ACTH)-independent macronodular adrenocortical
      hyperplasia (AIMAH). MATERIALS AND METHODS: Computed tomographic (CT) and
      magnetic resonance (MR) imaging findings in the adrenal glands were reviewed
      retrospectively in 12 patients (three men, nine women) with ACTH-independent
      Cushing syndrome and with bilateral nonpigmented multinodular adrenal
      hyperplasia. The results of pituitary MR imaging, adrenal scintigraphy, and
      petrosal sampling were available in nine, five, and six patients, respectively.
      Eleven patients underwent bilateral and one patient underwent unilateral
      adrenalectomy. RESULTS: Eleven patients had enlarged multinodular adrenal glands:
      Nodules were 0.1-5.5 cm. The combined weight of both adrenal specimens for the 11
      bilateral adrenalectomy specimens was 28-297 g, with a mean weight of 122 g.
      Glands were hypointense compared with the liver on T1-weighted images and were
      hyperintense on T2-weighted images. Pituitary MR imaging findings were negative
      in nine of nine patients. Iodomethylnorcholesterol scintigraphy showed bilateral
      uptake in four of five patients. Petrosal sinus sampling revealed no petrosal-to
      peripheral ACTH gradients before corticotropin-releasing hormone (CRH)
      stimulation in six of six patients, but three patients had gradients after CRH
      stimulation. After undergoing bilateral or unilateral adrenalectomy, all patients
      were cured. CONCLUSION: AIMAH is a rare cause of ACTH-independent Cushing
      syndrome, with characteristic CT findings of massively enlarged multinodular
      adrenal glands. Bilateral adrenalectomy is indicated on the basis of clinical and
      CT findings.

PMID- 10966716
TI  - Soft-copy quality control of digital spot images obtained by using X-ray image
      intensifiers.
AB  - PURPOSE: To evaluate 12 x-ray image intensifier (XRII) digital spot systems.
      MATERIALS AND METHODS: Four objective tests were performed to assess XRII digital
      spots: entrance exposure, patient exposure, soft-copy gray scale, and pixel
      noise. Two additional tests were performed to assess high-contrast limiting
      resolution and threshold contrast detection. RESULTS: Digital spot XRII entrance
      exposures averaged 1 x 10(-7) C/kg (0.38 mR) for units with large fields of view
      (FOVs); mean entrance exposure in a medium-sized patient was 1. 25 x 10(-5) C/kg
      (48 mR). Luminance measurements of the table-side monitors provided a mean of 473
      just-noticeable differences in gray scale with the room lights off. Mean
      resolution with a bar test pattern was measured as 1.5 line pairs per millimeter
      for systems with a 40-cm FOV. Measured pixel noise (in relative units) was 6-25.
      Mean threshold contrast with the lights off was 0.85%. CONCLUSION: Once input
      exposure is normalized for FOV and image matrix size, soft-copy assessment of
      limiting resolution with either low-contrast detection or, preferably, an off
      line noise metric (pixel SD) provides objective measurements of digital spot
      image quality. With the lights on, 10 systems with room-light sensors had an 11%
      loss of gray scale. For systems without sensors, the loss was 33%.

PMID- 10966715
TI  - Dynamic contrast-enhanced MR imaging of uterine cervical cancer: pharmacokinetic
      analysis with histopathologic correlation and its importance in predicting the
      outcome of radiation therapy.
AB  - PURPOSE: To investigate the histopathologic bases of different enhancement
      patterns on dynamic contrast material-enhanced magnetic resonance (MR) images of
      cervical cancer and to assess their importance in predicting the outcome of
      patients after radiation therapy. MATERIALS AND METHODS: Dynamic enhanced MR
      imaging and pharmacokinetic analyses were performed in 26 patients with cervical
      cancer who subsequently underwent hysterectomy and in 36 patients with cervical
      cancer who received radiation therapy. Histopathologic findings and clinical
      outcomes were correlated with results of dynamic MR imaging and pharmacokinetic
      analysis. RESULTS: On dynamic MR images of the surgical patients, areas with
      intense homogeneous enhancement showed increased permeability (k = 27.4 x 10(-3))
      compared with areas with poor enhancement (k = 19.0 x 10(-3)). Well-enhanced
      areas were predominantly composed of cancer cell fascicles, whereas poorly
      enhanced areas were composed of fibrous tissue with scattered cancer cells.
      Radiation therapy was more effective in tumors with higher tissue permeability (k
      = 31.3 x 10(-3)) on dynamic MR images than in those with lower tissue
      permeability (k = 18.3 x 10(-3)). CONCLUSION: Areas of increased contrast
      enhancement are mainly composed of abundant cancer cell fascicles, whereas poorly
      perfused areas are composed of fibrous tissue with scattered cancer cells.
      Radiation therapy is more effective in well-enhanced tumors, resulting in
      improved local control.

PMID- 10966717
TI  - Radiologists' preferences for digital mammographic display. The International
      Digital Mammography Development Group.
AB  - PURPOSE: To determine the preferences of radiologists among eight different image
      processing algorithms applied to digital mammograms obtained for screening and
      diagnostic imaging tasks. MATERIALS AND METHODS: Twenty-eight images representing
      histologically proved masses or calcifications were obtained by using three
      clinically available digital mammographic units. Images were processed and
      printed on film by using manual intensity windowing, histogram-based intensity
      windowing, mixture model intensity windowing, peripheral equalization, multiscale
      image contrast amplification (MUSICA), contrast-limited adaptive histogram
      equalization, Trex processing, and unsharp masking. Twelve radiologists compared
      the processed digital images with screen-film mammograms obtained in the same
      patient for breast cancer screening and breast lesion diagnosis. RESULTS: For the
      screening task, screen-film mammograms were preferred to all digital
      presentations, but the acceptability of images processed with Trex and MUSICA
      algorithms were not significantly different. All printed digital images were
      preferred to screen-film radiographs in the diagnosis of masses; mammograms
      processed with unsharp masking were significantly preferred. For the diagnosis of
      calcifications, no processed digital mammogram was preferred to screen-film
      mammograms. CONCLUSION: When digital mammograms were preferred to screen-film
      mammograms, radiologists selected different digital processing algorithms for
      each of three mammographic reading tasks and for different lesion types. Soft
      copy display will eventually allow radiologists to select among these options
      more easily.

PMID- 10966718
TI  - Uncommon high-risk lesions of the breast diagnosed at stereotactic core-needle
      biopsy: clinical importance.
AB  - PURPOSE: To assess the outcome of papillary lesions, radial scars, or lobular
      carcinoma in situ (LCIS) diagnosed at stereotactic core-needle biopsy (SCNB).
      MATERIALS AND METHODS: Retrospective review of 1,236 lesions sampled with SCNB
      yielded 22 papillary lesions, nine radial scars, and five LCIS lesions. Diffuse
      lesions such as papillomatosis, papillary ductal hyperplasia, papillary ductal
      carcinoma in situ (DCIS), and atypical lobular hyperplasia were not included. The
      mammographic findings, associated histologic features, and outcome were assessed
      for each case. RESULTS: Sixteen papillary lesions were diagnosed as benign at
      SCNB. Of these, five were benign at excision, and 10 were unremarkable at
      mammographic follow-up. At excision of an unusual lesion containing a microscopic
      papillary lesion, DCIS was found. Three of four papillary lesions suspicious at
      SCNB proved to be papillary carcinomas; the fourth had no residual carcinoma at
      excision. Eight of nine radial scars were excised, which revealed atypical
      hyperplasia in four scars but no malignancies. One LCIS lesion was found at
      excision to contain DCIS. CONCLUSION: Benign or malignant papillary lesions were
      accurately diagnosed with SCNB in the majority of cases. Cases diagnosed as
      suspicious for malignancy or with atypia or unusual associated histologic
      findings should be excised. No malignancies were found at excision of radial
      scars diagnosed at SCNB. Surgical removal of these lesions following SCNB may not
      be routinely necessary. DCIS was found in one lesion diagnosed as LCIS at SCNB,
      which suggests that removal of these lesions may be prudent.

PMID- 10966719
TI  - Linguine sign.

PMID- 10966720
TI  - Characteristics of triangular fibrocartilage defects in symptomatic and
      contralateral asymptomatic wrists.
AB  - PURPOSE: To characterize triangular fibrocartilage (TFC) defects in symptomatic
      and contralateral asymptomatic wrists. MATERIALS AND METHODS: Communicating and
      noncommunicating defects of the TFC were depicted on bilateral wrist arthrograms
      in 56 patients with unilateral wrist pain and without associated lesions of the
      scapholunate or lunotriquetral ligaments. The exact location of each TFC lesion
      was noted. RESULTS: Communicating defects were noted in 36 (64%) of 56
      symptomatic and in 26 (46%) of 56 asymptomatic wrists. Twenty-five (69%) of 36
      communicating defects were bilateral. Except for one defect in each group of
      symptomatic and asymptomatic wrists, all communicating defects were noted
      radially. Noncommunicating defects were noted in 28 (50%) of 56 symptomatic
      wrists and in 15 (27%) of 56 asymptomatic wrists. Eleven (39%) of 28
      noncommunicating defects were bilateral. On the symptomatic side, 28 of 36
      noncommunicating defects (including eight multiple defects) were located
      proximally at the ulnar side. On the asymptomatic side, 11 of 17 noncommunicating
      defects (including two multiple defects) were at or near the ulna. CONCLUSION:
      Noncommunicating TFC defects, which typically are located on the proximal side of
      the TFC near its ulnar attachment, have a more reliable association with
      symptomatic wrists than do communicating defects. Radial-sided communicating
      defects described in the literature (Palmer type 1A and 1D) as posttraumatic
      commonly are seen bilaterally and in asymptomatic wrists.

PMID- 10966721
TI  - Scapholunate ligamentous communicating defects in symptomatic and asymptomatic
      wrists: characteristics.
AB  - PURPOSE: To determine whether the sizes and locations of scapholunate ligamentous
      communicating defects are different in symptomatic and asymptomatic cases.
      MATERIALS AND METHODS: Bilateral wrist arthrograms were reviewed for 30
      consecutive patients with a history of wrist trauma and unilateral wrist pain who
      had at least one scapholunate ligamentous communicating defect and unremarkable
      conventional radiographs. The location and size of each ligamentous defect was
      recorded. Differences between symptomatic and asymptomatic wrists were analyzed
      with the chi(2) or Fisher exact test. RESULTS: Most communicating defects in both
      groups were incomplete and ranged from pinhole size to large. There was a higher
      frequency of complete disruption in the symptomatic wrists (nine [32%] of 28
      wrists) than in the asymptomatic wrists (two [10%] of 20 wrists; P: =.092).
      Communicating defects involved the dorsal portion in 18 (64%) of the 28
      symptomatic cases and in five (25%) of the 20 asymptomatic cases (P: =.007).
      CONCLUSION: The data suggest that the demonstration of a complete ligamentous
      disruption or involvement of the dorsal portion of the ligament may indicate a
      traumatic cause rather than a degenerative change.

PMID- 10966722
TI  - Dual-detector spiral CT arthrography of the knee: accuracy for detection of
      meniscal abnormalities and unstable meniscal tears.
AB  - PURPOSE: To determine the sensitivity and specificity of dual-detector spiral
      computed tomographic (CT) arthrography of the knee in the detection of meniscal
      abnormalities and unstable meniscal tears. MATERIALS AND METHODS: The meniscal
      changes in 50 consecutive patients who underwent dual-detector spiral CT of the
      knee after intraarticular injection of iodinated contrast material (0.55-mm
      effective section thickness, 0.75 pitch value, 0.3-mm increment reconstruction,
      0.43-mm in-plane resolution, 0.3-mm longitudinal resolution) were determined by
      two observers and were compared with arthroscopic findings. The sensitivity and
      specificity of CT arthrography for the detection of meniscal abnormalities and
      unstable meniscal tears and the kappa statistics for assessing interobserver
      reproducibility were determined. RESULTS: The sensitivity and specificity for the
      detection of meniscal abnormalities were 98% and 94%, respectively. The
      sensitivity and specificity for the detection of unstable meniscal tears were 97%
      and 90%, respectively. Interobserver agreement was excellent for the detection of
      meniscal abnormalities (kappa = 0.899) and of unstable meniscal tears (kappa =
      0.885). CONCLUSION: Dual-detector spiral CT arthrography of the knee is an
      accurate and reproducible method for detecting meniscal abnormalities and
      unstable meniscal tears.

PMID- 10966723
TI  - Femoral trochlear dysplasia: MR findings.
AB  - PURPOSE: To establish quantitative and qualitative magnetic resonance (MR)
      criteria for the diagnosis of trochlear dysplasia. MATERIALS AND METHODS: MR
      images were analyzed in 16 consecutive patients with and 23 without trochlear
      dysplasia. The standard of reference was a true lateral radiograph of the knee.
      Quantitative and qualitative MR criteria were assessed. RESULTS: In patients with
      trochlear dysplasia, the trochlear groove was significantly less deep than that
      in control subjects. The most accurate measurement was 3 cm above the
      femorotibial joint space (P: <.001), where a trochlear depth of 3 mm or less had
      a sensitivity of 100% and a specificity of 96%. The ventral trochlear prominence
      between the supratrochlear femoral cortex and the most ventral point of the
      trochlear floor (midsagittal section) was always larger than 6.9 mm in dysplastic
      trochleae. A facet ratio of less than 2:5 (medial to lateral) 3 cm above joint
      space level had a sensitivity of 100% and a specificity of 96%. A nipplelike
      anterior prominence at the superior end of the femoral trochlea on midsagittal
      images was a specific (91%) qualitative criterion. CONCLUSION: Dysplasia of the
      femoral trochlea can be diagnosed reliably by using quantitative or qualitative
      criteria on midsagittal or transverse MR images obtained 3 cm above the
      femorotibial joint space.

PMID- 10966724
TI  - Combined hepatocyte-selective and blood-pool contrast agents for the CT detection
      of experimental liver tumors in rabbits.
AB  - PURPOSE: To determine the imaging characteristics of a new computed tomographic
      (CT) contrast material with both hepatocyte-selective and blood-pool components
      (iodinated triglyceride (ITG)-dual) versus standard iohexol. MATERIALS AND
      METHODS: VX2 carcinoma was inoculated in seven rabbits. Animals underwent
      nonenhanced, iohexol-enhanced (600 mg of iodine per kilogram of body weight), and
      ITG-dual-enhanced (blood-pool moiety, 100 mg of iodine per kilogram; hepatocyte
      selective moiety, 100 or 200 mg of iodine per kilogram, injected 90 minutes
      apart) helical CT. Livers were removed, preserved in formalin, suspended in agar,
      and sectioned transversely at 3-mm intervals. Attenuation values for normal liver
      and tumors were obtained, and blinded readers evaluated images for lesions by
      using a modified free-response receiver operating characteristic (ROC) method.
      RESULTS: A total of 47 separate tumor sites were detected at pathologic
      examination. ITG-dual-enhanced scans obtained with 300 mg of iodine per kilogram
      demonstrated similar liver opacification to iohexol-enhanced scans obtained with
      600 mg of iodine per kilogram, but with less lesion enhancement, which resulted
      in better liver-to-lesion contrast. Blinded readers had a higher sensitivity,
      accuracy, and area under the ROC curve for ITG-dual-enhanced scans as compared
      with iohexol-enhanced scans (P: <.01). CONCLUSION: ITG-dual-enhanced CT
      quantitatively and qualitatively improved liver lesion detection versus iohexol
      enhanced CT. Future clinical trials with various human tumor types after
      potential approval for human use are needed to determine the ultimate role of
      this or other dual-mechanism contrast materials.

PMID- 10966725
TI  - Multiphasic injection method for uniform prolonged vascular enhancement at CT
      angiography: pharmacokinetic analysis and experimental porcine model.
AB  - PURPOSE: To determine if multiphasic injection provides uniform, prolonged
      vascular contrast medium enhancement at computed tomographic (CT) angiography.
      MATERIALS AND METHODS: With a computer-based, compartmental model of the
      cardiovascular system, theoretic analysis was performed to estimate an injection
      algorithm for uniform, prolonged vascular enhancement. For algorithm validation,
      four pigs were scanned after intravenous injection of 50 or 70 mL of contrast
      medium (282 mg of iodine per milliliter). Uni-, bi-, and multiphasic injection
      schemes were tested. In most cases, the initial injection rate was 2 mL/sec. In
      each CT study, 27 dynamic images were acquired every 2 seconds at a fixed mid
      abdominal aortic level. Time-enhancement curves were calculated. Injection
      duration, peak aortic enhancement, and enhancement uniformity (duration of
      enhancement achieved within 90% of the peak [90% DCE]) were evaluated. RESULTS:
      Theoretic and experimental results agreed well. Compared with uniphasic
      injection, biphasic injection resulted in more prolonged enhancement but
      generated two enhancement peaks with a valley between, and multiphasic injection
      yielded more uniform and prolonged enhancement. With 50- and 70-mL multiphasic
      injections, respectively, injection duration increased by 32% and 51%, peak
      enhancement decreased by 19% and 18%, and 90% DCE increased by 81% and 94%.
      CONCLUSION: Uniform, prolonged vascular enhancement, which is desirable for CT
      angiography and essential for steady-state quantification of blood volume in
      organs, can be achieved with multiphasic injection.

PMID- 10966726
TI  - Diffusional anisotropy in cranial nerves with maturation: quantitative evaluation
      with diffusion MR imaging in rats.
AB  - PURPOSE: To investigate the correlation between diffusional anisotropy and
      developmental changes in anatomy, which include myelination, in central and
      peripheral nerves in an animal model by using quantitative diffusion magnetic
      resonance (MR) imaging and electron microscopy. MATERIALS AND METHODS: In vivo
      transverse and longitudinal apparent diffusion coefficients (ADCs) of the optic
      and trigeminal nerves in 2-10-week-old rats were measured with MR imaging. Then
      the animals were sacrificed at each time point, and transverse and longitudinal
      sections of optic and trigeminal nerves were studied with electron microscopy.
      RESULTS: In the optic nerve, the ADC parallel to the neurofibers increased with
      development and increased contemporaneously with myelination, while the ADC
      perpendicular to the nerve did not change. This resulted in a significant
      increase in diffusional anisotropy. There were no significant changes in ADCs in
      either direction in the trigeminal nerve. Longitudinal sections of optic nerve
      showed a marked change in the orientation of each fiber. As development
      proceeded, the axons, which initially followed tortuous courses, assumed
      straighter and more parallel orientations. Trigeminal nerves displayed straight
      parallel courses at 2 weeks that did not change over the study period.
      CONCLUSION: Changes in fiber anatomy in maturation from tortuous to straighter
      and more parallel orientation can account for changes in longitudinal ADC and in
      diffusional anisotropy.

PMID- 10966727
TI  - Brachial plexus nerve block with CT guidance for regional pain management:
      initial results.
AB  - Brachial plexus nerve blocks are performed to treat patients with chronic pain
      referable to the brachial plexus. The needle insertion and trajectory are based
      on palpation of surface landmarks. Occasionally, the surface landmarks are
      difficult to identify owing to body habitus or anatomic alterations secondary to
      surgery or radiation therapy. The intent of this manuscript is to describe a
      technique for brachial plexus block guided with computed tomography and to report
      our initial results for regional pain management.

PMID- 10966728
TI  - Optimized single-slab three-dimensional spin-echo MR imaging of the brain.
AB  - The development and optimization of spin-echo-based, single-slab, three
      dimensional techniques for magnetic resonance imaging of the whole brain are
      described. T1-weighted and T2-weighted image sets with a volume resolution of 1
      mm(3) and fluid-attenuated inversion-recovery image sets with a volume resolution
      of 3 mm(3) were obtained in acquisition times of less than 10 minutes per image
      set.

PMID- 10966729
TI  - Anatomic MR images obtained with silent sequences.
AB  - The authors evaluated silent magnetic resonance (MR) imaging sequences for their
      suitability in providing high-spatial-resolution anatomic images that are of
      sufficient quality to be useful in a clinical setting. The authors compared the
      images obtained with a silent rapid acquisition with relaxation enhancement
      (RARE) sequence to its standard counterpart with respect to signal-to-noise
      ratio, distribution of gray level, and spatial resolution. No real differences
      were observed between the standard and the silent RARE MR images. Anatomic images
      were also acquired with a silent spin-echo sequence. Acoustic noise levels with
      the silent sequences were at least 22 dB (A-weighted scale) lower than those with
      standard sequences, without loss of image quality.

PMID- 10966730
TI  - Hepatic malignancies: improved detection with pulse-inversion US in late phase of
      enhancement with SH U 508A-early experience.
AB  - Twenty consecutive patients with known liver malignancies underwent
      ultrasonography (US) in conventional B mode and in pulse-inversion mode in the
      late hepatic-specific parenchymal phase after intravenous administration of SH U
      508A, a microbubble US contrast agent. Two experienced readers assessed
      subjective and objective conspicuity, number of lesions, and smallest lesion
      diameter in each mode. Subjective and objective conspicuity were improved with
      pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode
      than with conventional B mode, improving the detection of metastases less than 1
      cm in size.

PMID- 10966731
TI  - Abdomen, pelvis, and extremities: diagnostic accuracy of dynamic contrast
      enhanced turbo MR angiography compared with conventional angiography-initial
      experience.
AB  - To determine the value of contrast material-enhanced three-dimensional turbo
      magnetic resonance (MR) angiography compared with conventional cut-film or
      digital subtraction angiography for evaluating arterial stenosis in the abdomen,
      pelvis, and extremities. For detection of significant stenosis, MR angiography
      had 91% sensitivity and 89% specificity. This technique is highly sensitive in
      lesion detection, but stenosis tended to be overestimated.

PMID- 10966732
TI  - Nonenhanced CT for suspected appendicitis.

PMID- 10966733
TI  - Nonenhanced CT for suspected appendicitis.

PMID- 10966734
TI  - Endoanal MR is really complementary to endoanal US.

PMID- 10966735
TI  - Acute stroke: how to improve CT detection and avoid errors in radiology.

PMID- 10966736
TI  - Abstracts of Current Literature.

PMID- 10966737
TI  - Neurosteroid analogues. 8. Structure-activity studies of N-acylated 17a-aza-D
      homosteroid analogues of the anesthetic steroids (3alpha, 5alpha)- and
      (3alpha,5beta)-3-hydroxypregnan-20-one.

PMID- 10966738
TI  - Discovery of potent antagonists of the interaction between human double minute 2
      and tumor suppressor p53.

PMID- 10966739
TI  - Conformationally constrained analogues of diacylglycerol (DAG). 17. Contrast
      between sn-1 and sn-2 DAG lactones in binding to protein kinase C.
AB  - In previous work, we have obtained potent protein kinase C (PK-C) ligands with
      low-namomolar binding affinities by constructing diacylglycerol (DAG) mimetics in
      which the sn-2 carbonyl of DAG was constrained into a lactone ring. An additional
      structural element that helped achieve high binding affinity was the presence of
      branched acyl or alpha-alkylidene chains. In the present study, the effects of
      similarly branched chains on a different lactone system, where the lactone
      carbonyl is now equivalent to the sn-1 carbonyl of DAG, are investigated. In this
      new lactone template, the two chiral centers must have the S-configuration for
      enzyme recognition. As with the sn-2 DAG lactones, the branched chains were
      designed to optimize van der Waals contacts with a group of conserved hydrophobic
      amino acids located on the rim of the C1 domain of PK-C. The acyl and alpha
      alkylidene chains were also designed to be lipophilically equivalent (8 carbons
      each). Eight new compounds (7-14) representing all possible combinations of
      linear and branched acyl and alpha-alkylidene were synthesized and evaluated. The
      sn-1 DAG lactones were less effective as PK-C ligands than the sn-2 DAG lactones
      despite having a similar array of linear or branched acyl and alpha-alkylidene
      chains

PMID- 10966740
TI  - Benzothiadiazine dioxide dibenzyl derivatives as potent human cytomegalovirus
      inhibitors: synthesis and comparative molecular field analysis.
AB  - The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human
      cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure
      activity relationship study of these compounds, we have now synthesized N,N- and
      N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl,
      electron-donating, electron-withdrawing) in the phenyl ring of the benzyl
      moieties. The antiviral activity against HCMV (AD-169 strain) was also
      experimentally measured showing IC(50) values between 2.5 and 50 microM.
      Comparative molecular field analysis (CoMFA) was employed to generate a model,
      based upon 32 diverse BTD derivatives, to delineate structural and electrostatic
      features important for enhanced activity against HCMV. The steric (van der Waals)
      interactions with the receptor majoritary describes the variation in antiviral
      activity among the inhibitors. Finally, the CoMFA model was used to design two
      sets of novel BTD derivatives. Synthesis and subsequent anti-HCMV evaluation of
      these compounds enabled us to maintain the activity of this new kind of HCMV
      inhibitors.

PMID- 10966741
TI  - Crystal structures of human factor Xa complexed with potent inhibitors.
AB  - Involved in the coagulation cascade, factor Xa (FXa) is a serine protease which
      has received great interest as a potential target for the development of new
      antithrombotics. Although there is a great wealth of structural data on thrombin
      complexes, few structures of ligand/FXa complexes have been reported, presumably
      because of the difficulty in growing crystals. Reproducible crystallization
      conditions for human des-Gla1-45 coagulation FXa have been found. This has led to
      an improvement in the diffraction quality of the crystals (about 2.1 A) when
      compared to the previously reported forms (2.3-2.8 A) thus providing a suitable
      platform for a structure-based drug design approach. A series of crystal
      structures of noncovalent inhibitors complexed with FXa have been determined,
      three of which are presented herein. These include compounds containing the
      benzamidine moiety and surrogates of the basic group. The benzamidine-containing
      compound binds in a canonical fashion typical of synthetic serine protease
      inhibitors. On the contrary, molecules that contain surrogates of the benzamidine
      group do not make direct hydrogen-bonding interactions with the carboxylate of
      Asp189 at the bottom of the S1 pocket. The structural data provide a likely
      explanation for the specificity of these inhibitors and a great aid in the design
      of bioavailable potent FXa inhibitors.

PMID- 10966742
TI  - GRid-INdependent descriptors (GRIND): a novel class of alignment-independent
      three-dimensional molecular descriptors.
AB  - Traditional methods for performing 3D-QSAR rely upon an alignment step that is
      often time-consuming and can introduce user bias, the resultant model being
      dependent upon and sensitive to the alignment used. There are several methods
      which overcome this problem, but in general the necessary transformations prevent
      a simple interpretation of the resultant models in the original descriptor space
      (i.e. 3D molecular coordinates). Here we present a novel class of molecular
      descriptors which we have termed GRid-INdependent Descriptors (GRIND). They are
      derived in such a way as to be highly relevant for describing biological
      properties of compounds while being alignment-independent, chemically
      interpretable, and easy to compute. GRIND are obtained starting from a set of
      molecular interaction fields, computed by the program GRID or by other programs.
      The procedure for computing the descriptors involves a first step, in which the
      fields are simplified, and a second step, in which the results are encoded into
      alignment-independent variables using a particular type of autocorrelation
      transform. The molecular descriptors so obtained can be used to obtain graphical
      diagrams called "correlograms" and can be used in different chemometric analyses,
      such as principal component analysis or partial least-squares. An important
      feature of GRIND is that, with the use of appropriate software, the original
      descriptors (molecular interaction fields) can be regenerated from the
      autocorrelation transform and, thus, the results of the analysis represented
      graphically, together with the original molecular structures, in 3D plots. In
      this respect, the article introduces the program ALMOND, a software package
      developed in our group for the computation, analysis, and interpretation of
      GRIND. The use of the methodology is illustrated using some examples from the
      field of 3D-QSAR. Highly predictive and interpretable models are obtained showing
      the promising potential of the novel descriptors in drug design.

PMID- 10966743
TI  - 4-Anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth
      factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7
      dialkoxyquinazoline inhibitors.
AB  - The synthesis and SAR of a series of 4-anilino-6, 7-dialkoxyquinoline-3
      carbonitrile inhibitors of epidermal growth factor receptor (EGF-R) kinase are
      described. Condensation of 3, 4-dialkoxyanilines with ethyl
      (ethoxymethylene)cyanoacetate followed by thermal cyclization gave,
      regiospecifically, 6,7-dialkoxy-4-oxo-1, 4-dihydroquinoline-3-carbonitriles.
      Chlorination (POCl(3)) followed by the reaction with substituted anilines
      furnished the 4-anilino-6, 7-dialkoxyquinoline-3-carbonitrile inhibitors of EGF-R
      kinase. An alternate synthesis of these compounds starts with a methyl 3, 4
      dialkoxybenzoate. Nitration followed by reduction (Fe, NH(4)Cl, MeOH-H(2)O) gave
      a methyl 2-amino-4,5-dialkoxybenzoate. Amidine formation using DMF-acetal
      followed by cyclization using LiCH(2)CN furnished a 6,7-dialkoxy-4-oxo-1,4
      dihydroquinoline-3-carbonitrile, which was transformed as before. Compounds
      containing acid, ester, amide, carbinol, and aldehyde groups at the 3-position of
      the quinoline ring were also prepared for comparison, as were several 1-anilino
      6,7-dimethoxyisoquinoline-4-carbonitriles. The compounds were evaluated for their
      ability to inhibit the autophosphorylation of the catalytic domain of EGF-R. The
      SAR of these inhibitors with respect to the nature of the 6,7-alkoxy groups, the
      aniline substituents, and the substituent at the 3-position was studied. The
      compounds were further evaluated for their ability to inhibit the growth of cell
      lines that overexpress EGF-R or HER-2. It was found that 4-anilinoquinoline-3
      carbonitriles are effective inhibitors of EGF-R kinase with activity comparable
      to the 4-anilinoquinazoline-based inhibitors. A new homology model of EGF-R
      kinase was constructed based on the X-ray structures of Hck and FGF receptor-1
      kinase. The model suggests that with the quinazoline-based inhibitors, the N3
      atom is hydrogen-bonded to a water molecule which, in turn, interacts with Thr
      830. It is proposed that the quinoline-3-carbonitriles bind in a similar manner
      where the water molecule is displaced by the cyano group which interacts with the
      same Thr residue.

PMID- 10966744
TI  - DNA binding, solubility, and partitioning characteristics of extended
      lexitropsins.
AB  - Four new ligands that bind to the minor groove of DNA have been designed,
      synthesized, and evaluated by DNA footprinting. Two of the ligands are polyamides
      containing central regions with five or six N-methylpyrrole units, conferring
      hydrophobicity and good binding affinity but without retaining the correct
      spacing for hydrogen bonding in the base of the minor groove. The two remaining
      ligands have central regions which are head-to-head-linked polyamides, in which
      the linker is designed to improve the phasing of hydrogen bonding of the ligand
      with the floor of the minor groove. The highest affinity was obtained with the
      two polypyrroles without headgroup spacers, indicating that H-bond phasing is
      secondary in determining affinity compared to the major hydrophobic driving
      force. With a dimethylaminoalkyl group, representing a moiety with modest base
      strength, at both ends, water solubility is good and pH-partition theory predicts
      that penetration through lipid membranes will be enhanced, compared to strongly
      basic amidine analogues of the alkaloid precursors. All four compounds bind to
      DNA, with strong selectivity for AT sequences but some tolerance of GC base pairs
      and subtle individual preferences. The data show that very high affinities can be
      anticipated for future compounds in this series, but drug design must take
      account of overall physicochemical properties as well as the details of hydrogen
      bonding between ligands and the floor of the minor groove.

PMID- 10966745
TI  - Nonnucleoside human cytomegalovirus inhibitors: synthesis and antiviral
      evaluation of (chlorophenylmethyl)benzothiadiazine dioxide derivatives.
AB  - A second generation of benzothiadiazine dioxide (BTD) derivatives was synthesized
      employing benzylation reactions mainly. The chlorophenylmethyl BTD derivatives
      showed activity against human cytomegalovirus (HCMV) with IC(50) values ranging
      from 3 to 10 microM. Their 50% cytotoxic concentrations were often >200 microM to
      lung fibroblast HEL cell proliferation and between 20 and 35 microM for
      lymphocyte CME cell growth. When cytotoxicity for cell morphology was considered,
      the minimum cytotoxic concentration for the different BTD derivatives varied
      between 5 and 200 microM. Some of the anti-HCMV compounds also showed activity
      against HIV-1 and HIV-2. The chlorophenylmethyl derivative 21 was active against
      a variety of HCMV clinical isolates from patients with different clinical
      manifestations and fully maintained its activity against a ganciclovir-resistant
      HCMV strain. The dibenzyl BTD derivatives did not inhibit HCMV protease, and
      preliminary pharmacological experiments revealed that their anti-HCMV action
      stems from interference with an early stage of the viral replicative cycle.

PMID- 10966746
TI  - Cholic acid derivatives as 1,2,4,5-tetraoxane carriers: structure and
      antimalarial and antiproliferative activity.
AB  - Cholic acid-derived 1,2,4,5-tetraoxanes were synthesized in order to explore the
      influence of steroid carrier on its antimalarial and antiproliferative activity
      in vitro. Starting with chiral ketones, cis and trans series of diastereomeric
      tetraoxanes were obtained, and the cis series was found to be approximately 2
      times as active as the trans against Plasmodium falciparum D6 and W2 clones. The
      same tendency was observed against human melanoma (Fem-X) and human cervix
      carcinoma (HeLa) cell lines. The amide C(24) termini, for the first time
      introduced into the carrier molecule of a tetraoxane pharmacophore, significantly
      enhanced both antimalarial and antiproliferative activity, as compared to the
      corresponding methyl esters, with cis-bis(N-propylamide) being most efficient
      against the chloroquine-susceptible D6 clone (IC(50) = 9.29 nM). cis- and trans
      bis(N-propylamides) were also screened against PBMC, and PHA-stimulated PBMC,
      showing a cytotoxicity/antimalarial potency ratio of 1/10 000.

PMID- 10966747
TI  - Chemical synthesis and pharmacology of 6- and 7-hydroxylated 2-carbomethoxy-3-(p
      tolyl)tropanes: antagonism of cocaine's locomotor stimulant effects.
AB  - In our efforts to identify molecules that might act as cocaine antagonists or
      cocaine partial agonists, efforts were made to further capitalize on our earlier
      finding regarding the ability of a 7-methoxylated pseudococaine analogue to act
      as a weak cocaine functional antagonist. Herein, a series of the 6- and 7
      hydroxylated WIN analogues possessing a boat or chair conformation of the tropane
      ring were prepared and tested for their ability to displace [(3)H]mazindol
      binding and to inhibit high-affinity monoamine uptake into rat brain nerve
      endings. These 6- and 7-hydroxylated WIN analogues were readily prepared by use
      of a classical Willstatter synthesis to construct an appropriately functionalized
      tropane ring followed by use of a Suzuki coupling reaction to introduce the aryl
      group at position 3. Reduction of the resulting tropene by use of SmI(2) or by
      catalytic hydrogenation followed by deprotection delivered the final target
      compounds. Some of these compounds were found to retain considerable affinity as
      inhibitors of the dopamine transporter (DAT) and the norepinephrine transporter
      (NET), but they were less potent inhibitors of the serotonin transporter (SERT).
      None of the compounds of the present series revealed any substantial potency
      difference in [(3)H]mazindol binding versus [(3)H]DA uptake, and failed to show
      "cocaine antagonism" when tested for their ability to prevent cocaine's
      inhibition of DA transport. However, one of these hydroxylated WIN analogues,
      namely 12b, which possesses nanomolar potency at the DAT and NET and micromolar
      potency at the SERT, when tested in vivo, was found capable of attenuating
      cocaine's locomotor activity (AD(50) = 94 mg/kg). Taken together, this work
      provides further support for our hypothesis that drugs that lack the ability to
      inhibit transport by all three monoaminergic transporters may exhibit "partial"
      cocaine-like properties, but act as cocaine antagonists. Consequently, it may
      prove valuable to examine the behavioral activity of other 6- and 7-substituted
      tropanes in animal behavioral paradigms in the search for a cocaine medication.

PMID- 10966749
TI  - A new class of antituberculosis agents.
AB  - Long-chain lipid envelopes are characteristic of mycobacteria such as those that
      cause tuberculosis and leprosy. Inhibition of fatty acid synthesis or elongation
      is a strategy demonstrated to be clinically effective against M. tuberculosis. A
      new class of compounds designed to inhibit the beta-ketoacyl synthase reaction of
      fatty acid synthesis has been developed. Of >30 compounds described, the most
      active were acetamides containing alkylsulfonyl substituents. Inhibitory
      activities were acutely sensitive to net charge, chain length, and degree of
      unsaturation. The most active compound 5 (alkyl = C(10)) contained a single
      methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75
      1.5 microg/mL, comparable to first-line antituberculosis drugs. These compounds
      are species-specific, exhibiting no significant activity against bacterial
      species other than M. tuberculosis and closely related strains. The synthesis,
      biological activity, and specificity of these compounds are described.

PMID- 10966748
TI  - Synthesis of potent agonists of the D-myo-inositol 1,4, 5-trisphosphate receptor
      based on clustered disaccharide polyphosphate analogues of adenophostin A.
AB  - Clustered disaccharide analogues of adenophostin A (2), i.e. mono-, di-, and
      tetravalent derivatives 6-8, respectively, were synthesized and evaluated as
      novel ligands for the tetrameric D-myo-inositol 1,4, 5-trisphosphate receptor
      (IP(3)R). The synthesis was accomplished via Sonogashira coupling of propargyl 2
      O-acetyl-5-O-benzyl-3-O-(3, 4-di-O-acetyl-2, 6-di-O-benzyl-alpha-D
      glucopyranosyl)-beta-D-ribofuranoside (16) with iodobenzene 18, 22, or 25,
      followed by deacetylation, phosphorylation, and deprotection. The abilities of
      the target compounds 6-8, as well as ribophostin 4, propylphostin 5, and IP(3)
      (1), to evoke Ca(2+) release from permeabilized hepatocytes or displacement of
      [(3)H]IP(3) from its receptor in hepatic membranes were compared. Although the
      binding affinities of 4-8 were similar, there were modest though significant
      differences in their potencies in Ca(2+) release assays: tetraphostin 8 > IP(3)
      approximately diphostin 7 > phenylphostin 6 > ribophostin 4 approximately
      propylphostin 5.

PMID- 10966750
TI  - Anti-Helicobacter pylori agents. 4. 2-(Substituted guanidino)-4-phenylthiazoles
      and some structurally rigid derivatives.
AB  - In order to find a new class of anti-Helicobacter pylori (H. pylori) agents, a
      series of 4-[(3-acetamido)phenyl]-2-(substituted guanidino)thiazoles and some
      structurally rigid analoges were synthesized and evaluated for antimicrobial
      activity against H. pylori. Among the compounds obtained, high anti-H. pyrori
      activities were observed in benzyl derivative 34 (MIC = 0.025 microg/mL) and
      phenethyl derivatives 35 and 36 (MIC = 0.037 microg/mL and 0.017 microg/mL).
      Though alkyl derivatives generally showed lower activity, the 2-methoxyethyl
      derivative 28 preserved significant activity (MIC = 0.32 microg/mL) and also
      exhibited more potent gastric antisecretory activity than ranitidine. Structural
      restriction by bridging between the thiazole and the phenyl rings with an alkyl
      chain did not improve the activity in this series.

PMID- 10966751
TI  - Symmetrical bis(heteroarylmethoxyphenyl)alkylcarboxylic acids as inhibitors of
      leukotriene biosynthesis.
AB  - Symmetrical bis(quinolylmethoxyphenyl)alkylcarboxylic acids were investigated as
      inhibitors of leukotriene biosynthesis and 4, 4-bis(4-(2
      quinolylmethoxy)phenyl)pentanoic acid sodium salt (47.Na) met our design
      parameters for a drug candidate (ABT-080). This compound was readily synthesized
      in three steps from commercially available diphenolic acid. Against intact human
      neutrophils, 47.Na inhibited ionophore-stimulated LTB(4) formation with an IC(50)
      = 20 nM. In zymosan-stimulated mouse peritoneal macrophages producing both LTC(4)
      and PGE(2), 47.Na showed 9000-fold selectivity for inhibition of LTC(4) (IC(50) =
      0.16 nM) over PGE(2) (IC(50) = 1500 nM). Preliminary pharmacokinetic evaluation
      in rat and cynomolgus monkey demonstrated good oral bioavailability and
      elimination half-lives of 9 and 5 h, respectively. Pharmacological evaluation of
      leukotriene inhibition with oral dosing was demonstrated in a rat pleural
      inflammation model (ED(50) = 3 mg/kg) and a rat peritoneal passive anaphylaxis
      model (LTB(4), ED(50) = 2.5 mg/kg; LTE(4), ED(50) = 1.0 mg/kg). In a model of
      airway constriction induced by antigen challenge in actively sensitized guinea
      pigs, 47.Na dosed orally blocked bronchoconstriction with an ED(50) = 0.4 mg/kg,
      the most potent activity we have observed for any leukotriene inhibitor in this
      model. The mode of inhibitory action of 47.Na occurs at the stage of 5
      lipoxygenase biosynthesis as it blocks both leukotriene pathways leading to
      LTB(4) and LTC(4) but not PGH(2) biosynthesis. However, 47.Na does not inhibit 5
      lipoxygenase catalysis in a broken cell enzyme assay; therefore it is likely that
      47.Na acts as a FLAP inhibitor.

PMID- 10966752
TI  - New histamine H(3)-receptor ligands of the proxifan series: imoproxifan and other
      selective antagonists with high oral in vivo potency.
AB  - Histamine H(3)-receptor antagonists of the proxifan series are described. The
      novel compounds possess a 4-(3-(phenoxy)propyl)-1H-imidazole structure and
      various functional groups, e.g., an oxime moiety, on the phenyl ring. Synthesis
      of the novel compounds and X-ray crystallography of one highly potent oxime
      derivative, named imoproxifan (4-(3-(1H-imidazol-4-yl)propyloxy)phenylethanone
      oxime), are described. Most of the title compounds possess high antagonist
      potency in histamine H(3)-receptor assays in vitro as well as in vivo in mouse
      CNS following po administration. Structure-activity relationships are discussed.
      Imoproxifan displays subnanomolar potency on a functional assay on synaptosomes
      of rat cerebral cortex (K(i) = 0.26 nM). In vivo, imoproxifan increases the
      central N(tau)-methylhistamine level with an ED(50) of 0.034 mg/kg po. A receptor
      profile on several functional in vitro assays was determined for imoproxifan,
      demonstrating high selectivity toward the histamine H(3) receptor for this
      promising candidate for further development.

PMID- 10966753
TI  - Design, synthesis, and pharmacological characterization of 4-[4, 4-dimethyl-3-(4
      hydroxybutyl)-5-oxo-2-thioxo-1-imidazolidinyl]- 2-iodobenzonitrile as a high
      affinity nonsteroidal androgen receptor ligand.
AB  - 4-[4, 4-Dimethyl-3-(4-hydroxybutyl)-5-oxo-2-thioxo-1-imidazolidinyl]-2-+ ++trif
      luoromethylbenzonitrile (RU 59063) is a prototype of a new class of high-affinity
      nonsteroidal androgen receptor (AR) ligands. The search for a radioiodinated AR
      ligand prompted us to synthesize 4-[4, 4-dimethyl-3-(4-hydroxybutyl)-5-oxo-2
      thioxo-1-imidazolidinyl]-2-i odo benzonitrile (DTIB) wherein the trifluoromethyl
      group of RU 59063 was substituted with the similarly hydrophobic iodine atom.
      DTIB displayed subnanomolar binding affinity (K(i) = 0.71 +/- 0.22 nM) for the
      rat AR in competitive binding assays. Additionally, DTIB demonstrated potent
      agonist activity, comparable to that of the natural androgen 5alpha
      dihydrotestosterone (DHT), in a cell-based functional assay (cotransfection
      assay). DTIB represents a new lead for the development of high-affinity
      radioiodinated AR radioligands.

PMID- 10966754
TI  - 3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist
      lacking a phenolic hydroxyl group.
AB  - The C(3)-substituent in morphinan opioids is of critical importance; the 3-OH
      group is usually associated with very much higher affinity for mu-receptors than
      H or -OMe. However in this series of 14beta-cinnamoylamino derivatives the
      codeinones (e.g. methoclocinnamox, MC-CAM) had unexpectedly high mu-opioid
      receptor affinity, similar to that of the morphinone (clocinnamox, C-CAM). The
      current report relates to the synthesis and in vitro evaluation of
      deoxyclocinnamox (DOC-CAM) which acted as a high-affinity opioid antagonist
      similar to C-CAM but with greater mu selectivity. Thus it appears that the C(3)
      substituent does not play a major role in the binding of the 14beta-cinnamoyl
      series and that the cinnamoyl group itself may in fact be the dominant binding
      feature.

PMID- 10966755
TI  - Strong reciprocity and human sociality.
AB  - Human groups maintain a high level of sociality despite a low level of
      relatedness among group members. This paper reviews the evidence for an
      empirically identifiable form of prosocial behavior in humans, which we call
      "strong reciprocity", that may in part explain human sociality. A strong
      reciprocator is predisposed to cooperate with others and punish non-cooperators,
      even when this behavior cannot be justified in terms of extended kinship or
      reciprocal altruism. We present a simple model, stylized but plausible, of the
      evolutionary emergence of strong reciprocity.

PMID- 10966756
TI  - A computational study of the effect of capillary network anastomoses and
      tortuosity on oxygen transport.
AB  - The objective of this study was to investigate the effects of capillary network
      anastomoses and tortuosity on oxygen transport in skeletal muscle, as well as the
      importance of muscle fibers in determining the arrangement of parallel
      capillaries. Countercurrent flow and random capillary blockage (e.g. by white
      blood cells) were also studied. A general computational model was constructed to
      simulate oxygen transport from a network of blood vessels within a rectangular
      volume of tissue. A geometric model of the capillary network structure, based on
      hexagonally packed muscle fibers, was constructed to produce networks of straight
      unbranched capillaries, capillaries with anastomoses, and capillaries with
      tortuosity, in order to examine the effects of these geometric properties.
      Quantities examined included the tissue oxygen tension and the capillary
      oxyhemoglobin saturation. The computational model included a two-phase simulation
      of blood flow. Appropriate parameters were chosen for working hamster cheek-pouch
      retractor muscle. Our calculations showed that the muscle-fiber geometry was
      important in reducing oxygen transport heterogeneity, as was countercurrent flow.
      Tortuosity was found to increase tissue oxygenation, especially when combined
      with anastomoses. In the absence of tortuosity, anastomoses had little effect on
      oxygen transport under normal conditions, but significantly improved transport
      when vessel blockages were present.

PMID- 10966757
TI  - Development of nerve connections under the control of neurotrophic factors:
      parallels with consumer-resource systems in population biology.
AB  - The development of connections between neurons and their target cells involves
      competition between axons for target-derived neurotrophic factors. Although the
      notion of competition is commonly used in neurobiology, the process is not well
      understood, and only a few formal models exist. In population biology, in
      contrast, the concept of competition is well developed and has been studied by
      means of many formal models of consumer-resource systems. Here we show that a
      recently formulated model of axonal competition can be rewritten as a general
      consumer-resource system. This allows neurobiological phenomena to be interpreted
      in population biological terms and, conversely, results from population biology
      to be applied to neurobiology. Using findings from population biology, we have
      studied two extensions of our axonal competition model. In the first extension,
      the spatial dimension of the target is explicitly taken into account. We show
      that distance between axons on their target mitigates competition and permits the
      coexistence of axons. The model can account for the fact that in many types of
      neurons a positive correlation exists between the size of the dendritic tree and
      the number of innervating axons surviving into adulthood. In the second
      extension, axons are allowed to respond to more than one neurotrophic factor. We
      show that this permits competitive exclusion among axons of one type, while at
      the same time there is coexistence with axons of another type innervating the
      same target. The model offers an explanation for the innervation pattern found on
      cerebellar Purkinje cells, where climbing fibres compete with each other until
      only a single one remains, which coexists with parallel fibre input to the same
      Purkinje cell.

PMID- 10966758
TI  - Integral rein control in physiology II: a general model.
AB  - We generalize the principle of integral rein control to include other systems
      which partition in such a way that the equilibrium values of some variables are
      not dependent on the equations governing those variables. Instead, they are
      determined by the dynamics of other, "regulator" variables. We improve our
      earlier model for the control of glucose by insulin and glucagon by relaxing the
      condition necessary for it to operate. The two hormones do not have to be
      inhibited in the same way; they need only respond to the same combination of
      their concentrations. We also present a model for the control of ionized calcium
      by PTH and calcitonin and suggest that the role of chromogranin A may be to
      stabilize an otherwise unstable system.

PMID- 10966759
TI  - The implications of variable remigration intervals for the assessment of
      population size in marine turtles.
AB  - Sea turtles nest on sandy beaches and tend to show high fidelity to specific
      nesting areas, but, despite this fidelity, the inter-annual variation in nesting
      numbers may be large. This variation may reflect the fact that turtles do not
      usually nest in consecutive years. Here, theoretical models are developed in
      which the interval between successive nesting years (the remigration interval)
      reflects conditions encountered on the feeding grounds, with good feeding years
      leading to a reduction in the remigration interval and vice versa. These simple
      models produce high levels of inter-annual variation in nesting numbers with, on
      occasion, almost no turtles nesting in some years even when the population is
      large and stable. The implications for assessing the size of sea turtle
      populations are considered.

PMID- 10966760
TI  - Habitat diversity and stability in a metapopulation.

PMID- 10966762
TI  - Self-maintenance and self-reproduction in an abstract cell model.
AB  - Living cells must maintain their membranes by active metabolism. The membrane is
      not static but a dynamic structure that has evolved along with its internal
      reactions. When we reflect on the emergence and evolution of primitive cells, we
      should not forget the mutual dependency between membranes and metabolic cycles
      inside the cell. In this paper, we present a simple abstract model of the self
      maintaining cell. A metabolic cycle will produce a self-assembling membrane that
      will enclose the metabolic cycle. We show that a self-maintaining cell has the
      potential to reproduce itself spontaneously. Further, we have demonstrated two
      different ways of cellular reproduction depending on the mobility of chemicals.
      In the first case, a cell releases autocatalytic chemicals that create new cells
      outside the mother cell. In the second case, a cell grows larger and divides
      itself into daughter cells by creating a new internal dividing membrane.

PMID- 10966761
TI  - The dynamic activation of colicin Ia channels in planar bilayer lipid membrane.
AB  - Dynamic activation of ion channels formed by colicin Ia incorporated into a
      planar bilayer lipid membrane (BLM) was investigated by the voltage clamp
      technique using different step voltage stimuli. We have demonstrated a critical
      resting interval, Deltat(c), between two identical successive voltage pulses. If
      the second pulse is applied within Deltat(c), it produces a predictable current
      response. On the contrary, if the second pulse is applied after Deltat(c), the
      current response cannot be reliably predicted. Computer simulations based on an
      idealized mathematical model, developed in this paper, qualitatively reproduce
      the system's dynamic responses to stimulus trains. The behavior of the ion
      channels, when the resting period exceeds Deltat(c), may be interpreted as a
      transient gain or loss or resetting of memory, as revealed by a specific sequence
      of electrical pulses used for stimulation.

PMID- 10966763
TI  - Towards a quantitative model of immunogenicity: counting pathways in sequence
      space.
AB  - One of the fundamental aims of structural biology is the identification of high
      affinity ligands for arbitrary receptors. The maturation of the antibody
      repertoire elegantly and robustly solves this problem through an evolutionary
      mechanism comprising repeated cycles of mutation and preferential replication. To
      understand better the limitations and biases of this process, we developed an
      interpretation of antibody maturation within the framework of sequence space and
      fitness landscapes. Several well-described phenomena can be directly derived from
      this framework, and new predictions can be made. Ultimately, this
      reconceptualization of the clonal selection process suggests a quantitative,
      testable model of immunogenicity.

PMID- 10966764
TI  - Within-host spatial dynamics of viruses and defective interfering particles.
AB  - Defective-interfering (DI) viruses arise spontaneously by deletion mutations. The
      shortened genomes of the DI particles cannot replicate unless they coinfect a
      cell with a wild-type virus. Upon coinfection, the DI genome replicates more
      quickly and outcompetes the wild type. The coinfected cell produces mostly DI
      viruses. At the population level, the abundances of DI and wild-type viruses
      fluctuate dramatically under some conditions. In other cases, the DI viruses
      appear to mediate persistent infections with relatively low levels of host cell
      death. This moderation of viral damage has led some to suggest DI particles as
      therapeutic agents. Previous mathematical models have shown that either
      fluctuation or persistence can occur for plausible parameter values. I develop
      new mathematical models for the population dynamics of DI and wild-type viruses.
      My work extends the theory by developing specific predictions that can be tested
      in the laboratory. These predictions, if borne out by experiment, will explain
      the key processes that control the diversity of observed outcomes. The most
      interesting prediction concerns the rate at which killed host cells are replaced.
      A low rate of replacement causes powerful epidemics followed by a crash in viral
      abundance. As the rate of replacement increases, the frequency of oscillations
      increases in DI and wild-type viral abundances, but the severity (amplitude) of
      the fluctuations declines. At higher replacement rates for host cells, nearly all
      cells become infected by DI particles and a low level of fluctuating, wild-type
      viremia persists.

PMID- 10966765
TI  - Biological effects of electromagnetic fields--mechanisms for the effects of
      pulsed microwave radiation on protein conformation.
AB  - Microwave exposure under "athermal" conditions occurs when no temperature rise
      can be measured by conventional thermometry. The existence of biological effects
      arising from the athermal exposure is still controversial, partly because of a
      lack of the linear dose response relation. We propose a model in which pulsed
      microwave radiation causes a triggering of the heat shock or stress response by
      altering the conformation of proteins through a transient heating of the protein
      and its close environment. We support this by modelling using the heat diffusion
      equation and show that pulsed exposure even when athermal can lead to transient
      temperature excursions outside the normal range. We propose that the power window
      phenomenon in which biological effects are observed at low power levels may be
      caused by an incomplete triggering of the heat shock response.

PMID- 10966766
TI  - Scaling effects in the fatigue strength of bones from different animals.
AB  - The bones of vertebrates are all made from the same basic material, despite a
      huge variation in size from one species to another. This introduces a problem:
      large structures are more prone to fatigue failure (stress fracture) than smaller
      structures made of the same material. This implies that bones in larger animals
      cannot withstand as much stress in daily use as bones in smaller animals. In
      fact, this is not the case, because all bones experience approximately the same
      stresses and strains in use. This implies a variation in the underlying material:
      bone material in large animals must have superior fatigue properties to offset
      the disadvantages of size. This hypothesis is tested here by reference to fatigue
      data from the literature, taken from a range of animals from cows to mice.
      Fatigue strength was plotted as a function of stressed volume and modelled
      mathematically using a Weibull distribution. This shows a general tendency for
      fatigue strength to reduce as volume increases. But when the volume effect is
      taken into account, there remains a tendency for bones from smaller animals to
      have lower fatigue strength. This can be modelled by a simple variation in one of
      the parameters in the Weibull equation, which defines the intrinsic fatigue
      strength of the material. When extrapolated to the size of the whole bone for
      each animal, all bones were found to have the same fatigue strength. This
      resolves the anomaly and implies a complex system in which the underlying
      structure of bone varies with animal size in order to cancel out scaling effects.

PMID- 10966768
TI  - Thiol-disulfide interchange a potential key to conformational change associated
      with amyloid fibril formation.

PMID- 10966767
TI  - A comparative study of mutations in Escherichia coli and Salmonella typhimurium
      shows that codon conservation is strongly correlated with codon usage.
AB  - Escherichia coli and Salmonella typhimurium are closely related species of
      enteric bacteria, having diverged from 120 to 160 million years ago, according to
      the estimate of Ochman & Wilson (1987. J. Mol. Evol.26, 74-86). In order to study
      base substitution mutations in the genomes of these bacteria, we have compared
      pairs of genes for the same product in the two species, and have selected a
      sample in which the protein length is the same in both E. coli and S.
      typhimurium. From the alignment of these gene pairs, we observe that frequently
      used codons are more conserved than infrequently used codons, i.e., the apparent
      mutation rate is higher for rare codons than for popular codons.

PMID- 10966769
TI  - Placing parallel stranded DNA in an evolutionary context.

PMID- 10966770
TI  - Identification of an epitope in the C terminus of normal prion protein whose
      expression is modulated by binding events in the N terminus.
AB  - We have characterized the epitopes of a panel of 12 monoclonal antibodies (Mabs)
      directed to normal human cellular prion protein (PrP(C)) using ELISA and Western
      blotting of recombinant PrP or synthetic peptide fragments of PrP. The first
      group of antibodies, which is represented by Mabs 5B2 and 8B4, reacts with PrP(23
      145), indicating that the epitopes for these Mabs are located in the 23 to 145 N
      terminal region of human PrP. The second group includes Mabs 1A1, 6H3, 7A9, 8C6,
      8H4, 9H7 and 2G8. These antibodies bind to epitopes localized within N-terminally
      truncated recombinant PrP(90-231). Finally, Mabs 5C3, 2C9 and 7A12 recognize both
      PrP(23-145) and PrP(90-231), suggesting that the epitopes for this group are
      located in the region encompassing residues 90 to 145. By Western blotting with
      PepSpot(TM), only three of Mabs studied (5B2, 8B4 and 2G8) bind to linear
      epitopes that are present in 13-residue long synthetic peptides corresponding to
      human PrP fragments. The remaining nine Mabs appear to recognize conformational
      epitopes. Two N terminus-specific Mabs were found to prevent the binding of the C
      terminus-specific Mab 6H3. This observation suggests that the unstructured N
      terminal region may influence the local conformation within the folded C-terminal
      domain of prion protein.

PMID- 10966771
TI  - Preferential binding of fd gene 5 protein to tetraplex nucleic acid structures.
AB  - The gene 5 protein of filamentous bacteriophage fd is a single-stranded DNA
      binding protein that binds non-specifically to all single-stranded nucleic acid
      sequences, but in addition is capable of specific binding to the sequence
      d(GT(5)G(4)CT(4)C) and the RNA equivalent r(GU(5)G(4)CU(4)C), the latter
      interaction being important for translational repression. We show that this
      sequence preference arises from the formation of a tetraplex structure held
      together by a central block of G-quartets, the structure of which persists in the
      complex with gene 5 protein. Binding of gene 5 protein to the tetraplex leads to
      formation of a approximately 170 kDa nucleoprotein complex consisting of four
      oligonucleotide strands and eight gene 5 protein dimers, with a radius of
      gyration of 45 A and an overall maximum dimension of 120-130 A. A model of the
      complex is presented that is consistent with the data obtained. It is proposed
      that the G-quartet may act as a nucleation site for binding gene 5 protein to
      adjacent single-stranded regions, suggesting a novel mechanism for translational
      repression.

PMID- 10966772
TI  - Extreme functional sensitivity to conservative amino acid changes on enzyme
      exteriors.
AB  - Mutagenesis studies and alignments of homologous sequences have demonstrated that
      protein function typically is compatible with a variety of amino-acid residues at
      most exterior non-active-site positions. These observations have led to the
      current view that functional constraints on sequence are minimal at these
      positions. Here, it is shown that this inference assumes that the set of
      acceptable residues at each position is independent of the overall sequence
      context. Two approaches are used to test this assumption. First, highly
      conservative replacements of exterior residues, none of which would cause
      significant functional disruption alone, are combined until roughly one in five
      have been changed. This is found to cause complete loss of function in vivo for
      two unrelated monomeric enzymes: barnase (a bacterial RNase) and TEM-1 beta
      lactamase. Second, a set of hybrid sequences is constructed from the 50 %
      identical TEM-1 and Proteus mirabilis beta-lactamases. These hybrids match the
      TEM-1 sequence except for a region at the C-terminal end, where they are random
      composites of the two parents. All of these hybrids are biologically inactive. In
      both experiments, complete loss of activity demonstrates the importance of
      sequence context in determining whether substitutions are functionally
      acceptable. Contrary to the prevalent view, then, enzyme function places severe
      constraints on residue identities at positions showing evolutionary variability,
      and at exterior non-active-site positions, in particular. Homologues sharing less
      than about two-thirds sequence identity should probably be viewed as distinct
      designs with their own sets of optimising features.

PMID- 10966773
TI  - Geometric analysis and comparison of protein-DNA interfaces: why is there no
      simple code for recognition?
AB  - Structural studies of protein-DNA complexes have shown that there are many
      distinct families of DNA-binding proteins, and have shown that there is no simple
      "code" describing side-chain/base interactions. However, systematic analysis and
      comparison of protein-DNA complexes has been complicated by the diversity of
      observed contacts, the sheer number of complexes currently available and the
      absence of any consistent method of comparison that retains detailed structural
      information about the protein-DNA interface. To address these problems, we have
      developed geometric methods for characterizing the local structural environment
      in which particular side-chain/base interactions are observed. In particular, we
      develop methods for analyzing and comparing spatial relationships at the protein
      DNA interface. Our method involves attaching local coordinate systems to the DNA
      bases and to the C(alpha) atoms of the peptide backbone (these are relatively
      rigid structural units). We use these tools to consider how the position and
      orientation of the polypeptide backbone (with respect to the DNA) helps to
      determine what contacts are possible at any given position in a protein-DNA
      complex. Here, we focus on base contacts that are made in the major groove, and
      we use spatial relationships in analyzing: (i) the observed patterns of side
      chain/base interactions; (ii) observed helix docking orientations; (iii)
      family/subfamily relationships among DNA-binding proteins; and (iv) broader
      questions about evolution, altered specificity mutants and the limits for the
      design of new DNA-binding proteins. Our analysis, which highlights differences in
      spatial relationships in different complexes and at different positions in a
      complex, helps explain why there is no simple, general code for protein-DNA
      recognition.

PMID- 10966774
TI  - Refined structure of desmodium yellow mottle tymovirus at 2.7 A resolution.
AB  - Desmodium yellow mottle virus is a 28 nm diameter, T=3 icosahedral plant virus of
      the tymovirus group. Its structure has been solved to a resolution of 2.7 A using
      X-ray diffraction analysis based on molecular replacement and phase extension
      methods. The final R value was 0.151 (R(free)=0.159) for 134,454 independent
      reflections. The folding of the polypeptide backbone is nearly identical with
      that of turnip yellow mosaic virus, as is the arrangement of subunits in the
      virus capsid. However, a major difference in the disposition of the amino
      terminal ends of the subunits was observed. In turnip yellow mosaic virus, those
      from the B and C subunits comprising the hexameric capsomeres formed an annulus
      about the interior of the capsomere, while the corresponding N termini of the
      pentameric capsomere A subunits were not visible at all in electron density maps.
      In Desmodium yellow mottle tymovirus, amino termini from the A and B subunits
      combine to form the annuli, thereby resulting in a much strengthened association
      between the two types of capsomeres and an, apparently, more stable capsid. The
      first 13 residues of the C subunit were invisible in electron density maps. Two
      ordered fragments of single-stranded RNA, seven and two nucleotides in length,
      were observed. The ordered water structure of the virus particle was delineated
      and required 95 solvent molecules per protein subunit.

PMID- 10966776
TI  - An integrated approach to the analysis and modeling of protein sequences and
      structures. I. Protein structural alignment and a quantitative measure for
      protein structural distance.
AB  - We have devised and implemented in PrISM (protein informatics system for
      modeling) a new measure of protein structural relationships, the protein
      structural distance (PSD). The PSD is designed to describe relationships between
      protein structures in quantitative rather than descriptive terms and is
      applicable both when two structures are very similar, and when they are very
      different. It is calculated with a structural alignment procedure that uses
      double dynamic programming to align secondary structure elements and an iterative
      rigid body superposition that minimizes the root-mean-square deviation of
      C(alpha) atoms. The alignment algorithm, as implemented on a modest workstation,
      is computationally efficient, allowing for large-scale structural comparisons.
      PSD scores for more than one and a half million pairs of proteins were calculated
      and compared to the discrete classification of proteins in the SCOP database. The
      PSD scores, which were obtained automatically, are in large part consistent with
      the manually derived classifications in SCOP. Discrepancies do arise, however,
      due, in part, to the fact that SCOP uses criteria other than structural
      similarity to derive classifications while the PrISM procedure is exclusively
      structure based. Analysis of PSD scores suggests that there is a continuous
      aspect of protein conformation space, even though various classification schemes
      are extremely useful. The use of a continuous measure for structural distance
      between all pairs of proteins allows us, as described in the two accompanying
      papers to derive sequence/structure relationships in a more quantitative way than
      has previously been possible. An important strength of the approach implemented
      in PrISM is its ability to address many different kinds of queries interactively,
      making its structural comparison procedure a convenient computational tool that
      complements structural classification databases such as SCOP and CATH.

PMID- 10966775
TI  - A-Tract bending: insights into experimental structures by computational models.
AB  - While solution structures of adenine tract (A-tract) oligomers have indicated a
      unique bend direction equivalent to negative global roll (commonly termed "minor
      groove bending"), crystallographic data have not unambiguously characterized the
      bend direction; nevertheless, many features are shared by all A-tract crystal and
      solution structures (e.g. propeller twisting, narrow minor grooves, and localized
      water spines). To examine the origin of bending and to relate findings to the
      crystallographic and solution data, we analyze molecular dynamics trajectories of
      two solvated A-tract dodecamers: 1D89, d(CGCGA(6)CG), and 1D98, d(CGCA(6)GCG),
      using a new general global bending framework for analyzing bent DNA and
      DNA/protein complexes. It is significant that the crystallographically-based
      initial structures are converted from dissimilar to similar bend directions
      equivalent to negative global roll, with the average helical-axis bend ranging
      from 10.5 degrees to 14.1 degrees. The largest bend occurs as positive roll of 12
      degrees on the 5' side of the A-tracts (supporting a junction model) and is
      reinforced by gradual curvature at each A-tract base-pair (bp) step (supporting a
      wedge model). The precise magnitude of the bend is subtly sequence dependent
      (consistent with a curved general sequence model). The conversion to negative
      global roll only requires small local changes at each bp, accumulated over
      flexible moieties both outside and inside the A-tract. In contrast, the control
      sequence 1BNA, d(CGCGA(2)TTCGCG), bends marginally (only 6.9 degrees ) with no
      preferred direction. The molecular features that stabilize the bend direction in
      the A-tract dodecamers include propeller twisting of AT base-pairs, puckering
      differences between A and T deoxyriboses, a narrow minor groove, and a stable
      water spine (that extends slightly beyond the A-tract, with lifetimes approaching
      0.2 ns). The sugar conformations, in particular, are proposed as important
      factors that support bent DNA. It is significant that all these curvature
      stabilizing features are also observed in the crystallographic structures, but
      yield overall different bending paths, largely due to the effects of sequences
      outside the A-tract. These results merge structural details reported for A-tract
      structures by experiment and theory and lead to structural and dynamic insights
      into sequence-dependent DNA flexibility, as highlighted by the effect of an A
      tract variant of a TATA-box element on bending and flexibility required for TBP
      binding.

PMID- 10966777
TI  - An integrated approach to the analysis and modeling of protein sequences and
      structures. II. On the relationship between sequence and structural similarity
      for proteins that are not obviously related in sequence.
AB  - Here, we discuss the relationship between protein sequence and protein structural
      similarity. It is established that a protein structural distance (PSD) of 2.0 is
      a threshold above which two proteins are unlikely to have a detectable pairwise
      sequence relationship. A precise correlation is established between the level of
      sequence similarity, defined by a normalized Smith-Waterman score, and the
      probability that two proteins will have a similar structure (defined by pairwise
      PSD<2). This correlation can be used in evaluating the likelihood for success in
      a comparative modeling procedure. We establish the existence of a correlation
      between sequence and structural similarity for pairs of proteins that are related
      in structure but whose sequence relationship is not detectable using standard
      pairwise sequence alignments. Although it is well known that there is a close
      relationship between sequence and structural similarity for pairwise sequence
      identities greater than about 30 %, there has been little discussion as to the
      possible existence of such a relationship for pairs of proteins in or below the
      twilight zone of sequence similarity (<25 % pairwise sequence identity). Possible
      implications of our results for the evolution of protein structure are discussed.

PMID- 10966779
TI  - Automatic protein design with all atom force-fields by exact and heuristic
      optimization.
AB  - A fully automatic procedure for predicting the amino acid sequences compatible
      with a given target structure is described. It is based on the CHARMM package,
      and uses an all atom force-field and rotamer libraries to describe and evaluate
      side-chain types and conformations. Sequences are ranked by a quantity akin to
      the free energy of folding, which incorporates hydration effects. Exact (Branch
      and Bound) and heuristic optimisation procedures are used to identifying highly
      scoring sequences from an astronomical number of possibilities. These sequences
      include the minimum free energy sequence, as well as all amino acid sequences
      whose free energy lies within a specified window from the minimum. Several
      applications of our procedure are illustrated. Prediction of side-chain
      conformations for a set of ten proteins yields results comparable to those of
      established side-chain placement programs. Applications to sequence optimisation
      comprise the re-design of the protein cores of c-Crk SH3 domain, the B1 domain of
      protein G and Ubiquitin, and of surface residues of the SH3 domain. In all
      calculations, no restrictions are imposed on the amino acid composition and
      identical parameter settings are used for core and surface residues. The best
      scoring sequences for the protein cores are virtually identical to wild-type.
      They feature no more than one to three mutations in a total of 11-16 variable
      positions. Tests suggest that this is due to the balance between various
      contributions in the force-field rather than to overwhelming influence from
      packing constraints. The effectiveness of our force-field is further supported by
      the sequence predictions for surface residues of the SH3 domain. More mutations
      are predicted than in the core, seemingly in order to optimise the network of
      complementary interactions between polar and charged groups. This appears to be
      an important energetic requirement in absence of the partner molecules with which
      the SH3 domain interacts, which were not included in the calculations. Finally, a
      detailed comparison between the sequences generated by the heuristic and exact
      optimisation algorithms, commends a note of caution concerning the efficiency of
      heuristic procedures in exploring sequence space.

PMID- 10966778
TI  - An integrated approach to the analysis and modeling of protein sequences and
      structures. III. A comparative study of sequence conservation in protein
      structural families using multiple structural alignments.
AB  - The information required to generate a protein structure is contained in its
      amino acid sequence, but how three-dimensional information is mapped onto a
      linear sequence is still incompletely understood. Multiple structure alignments
      of similar protein structures have been used to investigate conserved sequence
      features but contradictory results have been obtained, due, in large part, to the
      absence of subjective criteria to be used in the construction of sequence
      profiles and in the quantitative comparison of alignment results. Here, we report
      a new procedure for multiple structure alignment and use it to construct
      structure-based sequence profiles for similar proteins. The definition of
      "similar" is based on the structural alignment procedure and on the protein
      structural distance (PSD) described in paper I of this series, which offers an
      objective measure for protein structure relationships. Our approach is tested in
      two well-studied groups of proteins; serine proteases and Ig-like proteins. It is
      demonstrated that the quality of a sequence profile generated by a multiple
      structure alignment is quite sensitive to the PSD used as a threshold for the
      inclusion of proteins in the alignment. Specifically, if the proteins included in
      the aligned set are too distant in structure from one another, there will be a
      dilution of information and patterns that are relevant to a subset of the
      proteins are likely to be lost. In order to understand better how the same three
      dimensional information can be encoded in seemingly unrelated sequences,
      structure-based sequence profiles are constructed for subsets of proteins
      belonging to nine superfolds. We identify patterns of relatively conserved
      residues in each subset of proteins. It is demonstrated that the most conserved
      residues are generally located in the regions where tertiary interactions occur
      and that are relatively conserved in structure. Nevertheless, the conservation
      patterns are relatively weak in all cases studied, indicating that structure
      determining factors that do not require a particular sequential arrangement of
      amino acids, such as secondary structure propensities and hydrophobic
      interactions, are important in encoding protein fold information. In general, we
      find that similar structures can fold without having a set of highly conserved
      residue clusters or a well-conserved sequence profile; indeed, in some cases
      there is no apparent conservation pattern common to structures with the same
      fold. Thus, when a group of proteins exhibits a common and well-defined sequence
      pattern, it is more likely that these sequences have a close evolutionary
      relationship rather than the similarities having arisen from the structural
      requirements of a given fold.

PMID- 10966780
TI  - Multiple roles of prolyl residues in structure and folding.
AB  - To explore the ways that proline residues may influence the conformational
      options of a polypeptide backbone, we have characterized Pro-->Ala mutants of
      cellular retinoic acid-binding protein I (CRABP I). While all three Xaa-Pro bonds
      are in the trans conformation in the native protein and the equilibrium stability
      of each mutant is similar to that of the parent protein, each has distinct
      effects on folding and unfolding kinetics. The mutation of Pro105 does not alter
      the kinetics of folding of CRABP I, which indicates that the flexible loop
      containing this residue is passive in the folding process. By contrast,
      replacement of Pro85 by Ala abolishes the observable slow phase of folding,
      revealing that correct configuration of the 84-85 peptide bond is prerequisite to
      productive folding. Substitution of Pro39 by Ala yields a protein that folds and
      unfolds more slowly. Removal of the conformational constraint imposed by the
      proline ring likely raises the transition state barrier by increasing the
      entropic cost of narrowing the conformational ensemble. Additionally, the Pro-
      >Ala mutation removes a helix-termination signal that is important for efficient
      folding to the native state.

PMID- 10966781
TI  - Combining phage display and screening of cDNA expression libraries: a new
      approach for identifying the target antigen of an scFv preselected by phage
      display.
AB  - A potential method for identifying new tumor-specific antibody structures as well
      as tumor-associated antigens is by selecting scFv phage libraries on tumor cells.
      This phage display technique involves multiple rounds of phage binding to target
      cells, washing to remove non-specific phage and elution to retrieve specific
      binding phage. Although the binding properties of an isolated tumor-specific scFv
      can be evaluated by ELISA, FACS and immunohistochemistry, it still remains a
      challenge to define the corresponding antigen. Here, we provide evidence that the
      target antigen of a given scFv displayed on phages can be detected in an
      immobilized lambda phage cDNA expression library containing thousands of
      irrelevant clones. The library contained CD30-negative breast-cancer specific
      cDNA as well as human CD30 receptor cDNA. The interaction of anti-CD30 scFv
      phages and their target antigen after blotting onto nitrocellulose filters was
      documented under defined conditions. Screening of different ratios between CD30
      receptor and breast cancer specific clones (1:1 and 1:200) revealed that the CD30
      antigen could be detected by anti-CD30 scFv phages using at least 5x10(12) plaque
      forming units of filamentous phages per blot. These investigations demonstrate
      that it is possible to detect the target antigen of a preselected scFv displayed
      on filamentous phages in lambda phage cDNA expression libraries.

PMID- 10966782
TI  - Crystal structure of Dengue virus NS3 protease in complex with a Bowman-Birk
      inhibitor: implications for flaviviral polyprotein processing and drug design.
AB  - Dengue viruses are members of the Flaviviridae and cause dengue fever and the
      more severe dengue hemorrhagic fever. Although nearly 40 % of the world's
      population is at risk of dengue infection, there is currently no effective
      vaccine or chemotherapy for the disease. Processing of the dengue polyprotein
      into structural and non-structural proteins in a host, which is essential for
      assembly of infective virions, is carried out by the combined action of host
      proteases and the trypsin-like, two-component viral NS2B/NS3 serine protease.
      Although NS2B strongly stimulates the catalytic NS3 protease domain, the latter
      is fully active against small substrates and possesses detectable activity
      against larger substrates, making both forms of the enzyme possible targets for
      drug design. In the crystal structure of a complex of the protease with a Bowman
      Birk inhibitor reported here, an Arg residue at the P1 position of the inhibitor
      is bound in a manner distinctly different from that in other serine proteases of
      comparable specificity. However, because the regulatory component, NS2B, is not
      present in the complex, the physiological implications of this observations are
      currently unclear. The redundant nature of interaction of P1 Arg and Lys residues
      with Asp129, Tyr150 and Ser163 of the enzyme provides an explanation for the
      observed behavior of several site-specific mutants of Asp129 in the protease. The
      strong level of conservation of residues in the protease that interact with the
      P1 Arg, along with conservation of Arg at P1 of most cleavage sites in other
      flaviviruses, suggests that observations from this structure are likely to be
      applicable to many flaviviruses. The structure provides a starting point for
      design of site-specific mutations to probe the mechanism of catalysis by the
      catalytic domain, its activation by the regulatory domain and for design of
      specific inhibitors of enzymatic activity.

PMID- 10966783
TI  - Cytochrome c(553), a small heme protein that lacks misligation in its unfolded
      state, folds with rapid two-state kinetics.
AB  - Cytochrome c(553) (cyt c(553)) from Desulfovibrio vulgaris is a small helical
      heme protein that displays apparent two-state equilibrium-unfolding behavior. The
      covalently attached heme is low-spin, ligated by Met and His residues, in the
      native state but becomes high-spin upon unfolding at pH 7. Here, we show that in
      contrast to other c-type heme proteins, where misligations in the unfolded states
      are prominent, cyt c(553) refolding kinetics at pH 7 proceeds rapidly without
      detectable intermediates. The extrapolated folding rate constant in water for
      oxidized cyt c(553) matches exactly that predicted from the cyt c(553) native
      state topology: 5300 s(-1 )(experimental) versus 5020 s(-1) (predicted). We
      therefore conclude that the presence of the oxidized cofactor does not affect the
      intrinsic formation speed of the cyt c(553 )structural motif.

PMID- 10966784
TI  - The interconversion of isoforms of seminal ribonuclease: modelling key
      intermediates and trypsin effects.
AB  - The stepwise tryptic degradation of the interconverting quaternary isoforms of
      seminal ribonuclease has been analysed by structural modelling, based on the
      experimental results obtained by treating the dimeric protein with trypsin. The
      results of the analysis were compared with those obtained applying to the action
      of trypsin on seminal ribonuclease a recently proposed predictive algorithm for
      limited proteolysis. The attention was focussed on the MxM form of the protein,
      in which the two subunits swap their N-terminal ends interconverting at
      equilibrium with the M=M form with no interchange between subunits. The analysis
      led to the identification of a key intermediate in the interconversion pathway,
      and to the resolution of the apparent contradiction between prediction and actual
      experimental data.

PMID- 10966785
TI  - Examination of the transcription factor NtcA-binding motif by in vitro selection
      of DNA sequences from a random library.
AB  - A recursive in vitro selection among random DNA sequences was used for analysis
      of the cyanobacterial transcription factor NtcA-binding motifs. An eight-base
      palindromic sequence, TGTA-(N(8))-TACA, was found to be the optimal NtcA-binding
      sequence. The more divergent the binding sequences, compared to this consensus
      sequence, the lower the NtcA affinity. The second and third bases in each four
      nucleotide half of the consensus sequence were crucial for NtcA binding, and they
      were in general highly conserved. The most frequently occurring sequence in the
      middle weakly conserved region was similar to that of the NtcA-binding motif of
      the Anabaena sp. strain PCC 7120 glnA gene, previously known to have high
      affinity for NtcA. This indicates that the middle sequences were selected for
      high NtcA affinity. Analysis of natural NtcA-binding motifs showed that these
      could be classified into two groups based on differences in recognition consensus
      sequences. It is suggested that NtcA naturally recognizes different DNA-binding
      motifs, or has differential affinities to these sequences under different
      physiological conditions.

PMID- 10966786
TI  - FHX.L and FHX.S, two isoforms of the human fork-head factor FHX (FOXJ2) with
      differential activity.
AB  - Many biological phenomena are dependent on mechanisms that fine-tune the
      expression levels of particular genes. This can be achieved by altering the
      relative activity of a single transcription factor, by post-translational
      modifications or by interaction with regulatory molecules. An alternative
      mechanism is based on competition between two or more differently active isoforms
      of the same transcription factor. We found that FHX, a recently characterized
      human fork-head transcriptional activator, may show such a mechanism for
      balancing its activity by expressing two differently sized isoforms, FHX.S and
      FHX.L, encoded by a single gene located on human chromosome 12. FHX. L and FHX.S
      showed different transcriptional capacities, the larger form, FHX.L, behaving as
      the more potent transactivator. A transactivation domain of the acidic type
      present only in FHX.L would account for this functional difference. The relative
      concentrations of these two FHX isoforms appear to vary in a number of cell
      types, a circumstance that may regulate the final activity of this transcription
      factor.

PMID- 10966787
TI  - Identification of amino acid residues of transcription factor AP-2 involved in
      DNA binding.
AB  - AP-2 is a cell-type specific, developmentally regulated transcription factor
      which has been described as a critical regulator of gene expression during
      vertebrate development and embryogenesis. Although the overall domains of this
      factor necessary for their activity have been identified, the exact identity of
      AP-2 amino acid residues responsible for its interaction with the DNA structure
      has not yet been described. Here, we describe the identification of a region of
      AP-2 which was protected by an oligonucleotide probe containing its binding site
      from trypsin digestion, monitored by peptide mapping by MALDI-TOF mass
      spectrometry. Furthermore, we analyzed the relative in vitro DNA-binding
      activity, the stimulatory potency on the AP-2-dependent APOE promoter, as well as
      the ability to inhibit the effect of the wild-type protein of each one of a set
      of single-site substitution AP-2 mutants spanning the identified region. Taken
      together, our data clearly demonstrate that the region between amino acid
      residues 252-260 of AP-2 is essential for its DNA-binding activity. Particularly,
      the individual substitution in any of the residues 253, 254, 255, 257 or 260 is
      sufficient for completely abolishing the interaction with DNA and the stimulation
      of APOE promoter activity. These results indicate a crucial role of this region
      in the formation of an active DNA-binding domain and strongly suggest that these
      residues provide direct contacts with the DNA structure at the AP-2 binding site.

PMID- 10966788
TI  - A ribozyme derived from the catalytic subunit of RNase P from Escherichia coli is
      highly effective in inhibiting replication of herpes simplex virus 1.
AB  - A sequence-specific ribozyme (M1GS RNA) derived from the catalytic RNA subunit of
      RNase P from Escherichia coli was used to target the mRNA encoding human herpes
      simplex virus 1 (HSV-1) major transcription activator, ICP4. A reduction of more
      than 80% in the expression level of ICP4 and a reduction of about 1000-fold in
      viral growth were observed in cells that stably expressed the ribozyme. In
      contrast, a reduction of less than 10 % in ICP4 expression and viral growth was
      observed in cells that either did not express the ribozyme or produced a
      catalytically inactive ribozyme mutant. Thus, M1GS ribozyme is highly effective
      in inhibiting HSV-1 growth and can be used as a general gene-targeting agent for
      anti-HSV applications.

PMID- 10966789
TI  - Identification of residues involved in the specificity and regulation of the
      highly efficient multisubstrate deoxyribonucleoside kinase from Drosophila
      melanogaster.
AB  - In contrast to all known deoxyribonucleoside kinases, a single highly efficient
      deoxyribonucleoside kinase from Drosophila melanogaster (Dm-dNK) is able to
      phosphorylate all precursor nucleosides for DNA synthesis. Dm-dNK was mutated in
      vitro by high-frequency random mutagenesis, expressed in the thymidine kinase
      deficient Escherichia coli strain KY895 and clones were selected for sensitivity
      to the nucleoside analogs 1-beta-d-arabinofuranosylcytosine (AraC, Cytarabine),
      3'-azido-2', 3'-dideoxythymidine (AZT, Zidovudine, Retrovir, 2', 3'
      dideoxyadenosine (ddA) and 2',3'-dideoxycytidine (ddC, Zalcitabine, Hivid.
      Thirteen mutants with increased sensitivity compared to the wild-type Dm-dNK were
      isolated from a relatively small pool of less than 10,000 clones. Eight mutant Dm
      dNKs increased the sensitivity of KY895 to more than one analog, and two of these
      mutants even to all four nucleoside analogs. Surprisingly, the mutations did not
      map to the five regions which are highly conserved among deoxyribonucleoside
      kinases. The molecular background of improved sensitivity was characterized for
      the double-mutant MuD (N45D, N64D), where the LD(100) value of transformed KY895
      decreased 316-fold for AZT and more than 11-fold for ddC when compared to wild
      type Dm-dNK. Purified recombinant MuD displayed higher K(m) values for the native
      substrates than wild-type Dm-dNK and the V(max) values were substantially lower.
      On the other hand, the K(m) and V(max) values for AZT and the K(m) value for ddC
      were nearly unchanged between MuD and wild-type Dm-dNK. Additionally, a decrease
      in feedback inhibition of MuD by thymidine triphosphate (TTP) was found. This
      study demonstrates how high-frequency mutagenesis combined with a parallel
      selection for desired properties provides an insight into the structure-function
      relationships of the multisubstrate kinase from D. melanogaster. At the same time
      these mutant enzymes exhibit properties useful in biotechnological and medical
      applications.

PMID- 10966790
TI  - Functional interactions of Mycobacterium leprae RuvA with Escherichia coli RuvB
      and RuvC on holliday junctions.
AB  - The Mycobacterium leprae RuvA homologue (MlRuvA) was over-expressed in
      Escherichia coli and purified to homogeneity. The DNA-binding specificity and the
      functional interactions of MlRuvA with E. coli RuvB and RuvC (EcRuvB and EcRuvC)
      were examined using synthetic Holliday junctions. MlRuvA bound specifically to
      Holliday junctions and produced similar band-shift patterns as EcRuvA. Moreover,
      MlRuvA formed functional DNA helicase and branch-migration enzymes with EcRuvB,
      although the heterologous enzyme had a lower efficiency. These results
      demonstrate that the RuvA homologue of M. leprae is a functional branch-migration
      subunit. Whereas MlRuvA promoted branch-migration in combination with EcRuvB, it
      was unable to stimulate branch-migration-dependent resolution in a RuvABC
      complex. The inability to stimulate RuvC was not due to its failure to form
      heterologous RuvABC complexes on junctions, since such complexes were detected by
      co-immunoprecipitation. Most likely, the stability of the heterologous RuvABC
      complex and, possibly, the interactions between RuvA and RuvC were impaired, as
      gel-shift experiments failed to show mixed MlRuvA-EcRuvC-junction complexes.
      These results demonstrate that branch-migration per se and the assembly of a
      RuvABC complex on the Holliday junction are insufficient for RuvAB-dependent
      resolution of the junction by RuvC, suggesting that specific and intimate
      interactions between all three proteins are required for the function of a RuvABC
      "resolvasome".

PMID- 10966791
TI  - DNA polymerase lambda (Pol lambda), a novel eukaryotic DNA polymerase with a
      potential role in meiosis.
AB  - A new gene (POLL) encoding a novel DNA polymerase (Pol lambda) has been
      identified at mouse chromosome 19. Murine Pol lambda, consisting of 573 amino
      acid residues, has a 32% identity to Pol beta, involved in nuclear DNA repair in
      eukaryotic cells. It is interesting that Pol lambda contains all the critical
      residues involved in DNA binding, nucleotide binding and selection, and catalysis
      of DNA polymerization, that are conserved in Pol beta and other DNA polymerases
      belonging to family X. Murine Pol lambda, overproduced in Escherichia coli,
      displayed intrinsic DNA polymerase activity when assessed by in situ gel
      analysis. Pol lambda also conserves the critical residues of Pol beta required
      for its intrinsic deoxyribose phosphate lyase (dRPase) activity. The first 230
      amino acid residues of Pol lambda, that have no counterpart in Pol beta, contain
      a BRCT domain, present in a variety of cell-cycle check-point control proteins
      responsive to DNA damage and proteins involved in DNA repair. Northern blotting,
      in situ hybridization analysis and immunostaining showed high levels of Pol
      lambda specifically expressed in testis, being developmentally regulated and
      mainly associated to pachytene spermatocytes. These first evidences, although
      indirect, suggest a potential role of Pol lambda in DNA repair synthesis
      associated with meiosis.

PMID- 10966792
TI  - Reversible loss of crystallinity on photobleaching purple membrane in the
      presence of hydroxylamine.
AB  - Structural changes of purple membrane during photobleaching in the presence of
      hydroxylamine were monitored using atomic force microscopy (AFM). The process of
      bleaching was associated with the disassembly of the purple membrane crystal into
      smaller crystals. Imaging steps of the photobleaching progress showed that
      disassembly proceeds until the sample is fully bleached and its crystallinity is
      almost lost. As revealed from high resolution AFM topographs, the loss of
      crystallinity was initiated by loss of lattice forming contact between the
      individual bacteriorhodopsin trimers. The bacteriorhodopsin molecules, however,
      remained assembled into trimers during the entire photobleaching process.
      Regeneration of the photobleached sample into intact purple membrane resulted in
      the reassembly of the bacteriorhodopsin trimers into the trigonal lattice of
      purple membrane. The data provide novel insights into factors triggering purple
      membrane formation and structure.

PMID- 10966793
TI  - Time-resolved detection of transient movement of helix F in spin-labelled
      pharaonis sensory rhodopsin II.
AB  - Sensory rhodopsin II (also called phoborhodopsin) from the archaeal
      Natronobacterium pharaonis (pSRII) functions as a repellent phototaxis receptor.
      The excitation of the receptor by light triggers the activation of a transducer
      molecule (pHtrII) which has close resemblance to the cytoplasmic domain of
      bacterial chemotaxis receptors. In order to elucidate the first step of the
      signal transduction chain, the accessibility as well as static and transient
      mobility of cytoplasmic residues in helices F and G were analysed by electron
      paramagnetic resonance spectroscopy. The results indicate an outward tilting of
      helix F during the early steps of the photocycle which is sustained until the
      reformation of the initial ground state. Co-expression of pSRII with a truncated
      fragment of pHtrII affects the accessibility and/or the mobility of certain spin
      labelled residues on helices F and G. The results suggest that these sites are
      located within the binding surface of the photoreceptor with its transducer.

PMID- 10966794
TI  - Highly efficient selection of phage antibodies mediated by display of antigen as
      Lpp-OmpA' fusions on live bacteria.
AB  - Delayed infectivity panning (DIP) is a novel approach for the in vivo isolation
      of interacting protein pairs. DIP combines phage display and cell surface display
      of polypeptides as follows: an antigen is displayed in many copies on the surface
      of F(+) Escherichia coli cells by fusing it to a Lpp-OmpA' hybrid. To prevent
      premature, non-specific infection by phage, the cells are rendered functionally
      F(-) by growth at 16 degrees C. The antigen-displaying cells are used to capture
      antibody-displaying phage by virtue of the antibody-antigen interaction.
      Following removal of unbound phage, infection of the cells by bound phage is
      initiated by raising the temperature to 37 degrees C that facilitates F pilus
      expression. The phage then dissociate from the antigen and infect the bacteria
      through the F pilus. Using specific scFv antibodies and the human ErbB2 proto
      oncogene and IL2-Ralpha chain as model antibody-antigen pairs, we demonstrate
      enrichment of those phage that display a specific antibody over phage that
      display an irrelevant antibody of over 1,000,000 in a single DIP cycle. We
      further show the successful isolation of anti-toxin, anti-receptor, anti-enzyme
      and anti-peptide antibodies from several immune phage libraries, a shuffled
      library and a large synthetic human library. The effectiveness of DIP makes it
      suitable for the isolation of rare clones present in large libraries. Since DIP
      can be applied for most of the phage libraries already existing, it could be a
      powerful tool for the rapid isolation and characterization of binders in numerous
      protein-protein interactions.

PMID- 10966795
TI  - Membrane-induced conformational change during the activation of HIV-1 gp41.
AB  - The human immunodeficiency virus type 1 gp41 ectodomain forms a three-hairpin
      protease-resistant core in the absence of membranes, namely, the putative gp41
      fusion-active state. Here, we show that recombinant proteins corresponding to the
      ectodomain of gp41, but lacking the fusion peptide, bind membranes and
      consequently undergo a major conformational change. As a result, the protease
      resistant core becomes susceptible to proteolytic digestion. Accordingly,
      synthetic peptides corresponding to the segments that construct this core bind
      the membrane. It is remarkable that the hetero-oligomer formed by these peptides
      dissociates upon binding to the membrane. These results are consistent with a
      model in which, after the three-hairpin conformation is formed, membrane binding
      induces opening of the gp41 core complex. We speculate that binding of the
      segments that constructed the core to the viral and cellular membranes could
      bring the membranes closer together and facilitate their merging.

PMID- 10966797
TI  - Mutations in the glucocorticoid receptor DNA-binding domain mimic an allosteric
      effect of DNA.
AB  - Two previously isolated mutations in the glucocorticoid receptor DNA-binding
      domain (DBD), S459A and P493R, have been postulated to mimic DNA-induced
      conformational changes in the glucocorticoid receptor DBD, thereby constitutively
      triggering an allosteric mechanism in which binding of specific DNA normally
      induces the exposure of otherwise silent glucocorticoid receptor transcriptional
      activation surfaces. Here we report the three-dimensional structure of the free
      S459A and P493R mutant DBDs as determined by NMR spectroscopy. The free S459A and
      P493R structures both display the conformational changes in the DBD dimerization
      interface that are characteristic of the DNA-bound wild-type DBD, confirming that
      these mutations mimic an allosteric effect of DNA. A transition between two
      packing arrangements of the DBD hydrophobic core provides a mechanism for long
      range transmission of conformational changes, induced either by the mutations or
      by DNA binding, to protein-protein contact surfaces.

PMID- 10966796
TI  - 1 A crystal structures of B-DNA reveal sequence-specific binding and groove
      specific bending of DNA by magnesium and calcium.
AB  - The 1 A resolution X-ray crystal structures of Mg(2+) and Ca(2+) salts of the B
      DNA decamers CCAACGTTGG and CCAGCGCTGG reveal sequence-specific binding of Mg(2+)
      and Ca(2+) to the major and minor grooves of DNA, as well as non-specific binding
      to backbone phosphate oxygen atoms. Minor groove binding involves H-bond
      interactions between cross-strand DNA base atoms of adjacent base-pairs and the
      cations' water ligands. In the major groove the cations' water ligands can
      interact through H-bonds with O and N atoms from either one base or adjacent
      bases, and in addition the softer Ca(2+) can form polar covalent bonds bridging
      adjacent N7 and O6 atoms at GG bases. For reasons outlined earlier, localized
      monovalent cations are neither expected nor found.Ultra-high atomic resolution
      gives an unprecedented view of hydration in both grooves of DNA, permits an
      analysis of individual anisotropic displacement parameters, and reveals up to 22
      divalent cations per DNA duplex. Each DNA helix is quite anisotropic, and
      alternate conformations, with motion in the direction of opening and closing the
      minor groove, are observed for the sugar-phosphate backbone. Taking into
      consideration the variability of experimental parameters and crystal packing
      environments among these four helices, and 24 other Mg(2+) and Ca(2+) bound B-DNA
      structures, we conclude that sequence-specific and strand-specific binding of
      Mg(2+) and Ca(2+) to the major groove causes DNA bending by base-roll compression
      towards the major groove, while sequence-specific binding of Mg(2+) and Ca(2+) in
      the minor groove has a negligible effect on helix curvature. The minor groove
      opens and closes to accommodate Mg(2+) and Ca(2+) without the necessity for
      significant bending of the overall helix. The program Shelxdna was written to
      facilitate refinement and analysis of X-ray crystal structures by Shelxl-97 and
      to plot and analyze one or more Curves and Freehelix output files.

PMID- 10966798
TI  - Interactions of Arg2 in the Mnt N-terminal arm with the central and flanking
      regions of the Mnt operator.
AB  - Arg2, in the N-terminal arm of the Mnt repressor, plays an important role in
      determining operator-binding specificity. In the complex of the Mnt tetramer with
      the 21 base-pair mnt operator, there are four potential sites for Arg2
      interactions, two in the central region of the operator and two on the outer
      flanks of the operator. Single-chain variants of the dimeric N-terminal domain of
      Mnt containing one Arg2 residue and one Lys2 or Met2 residue were constructed and
      interactions with operator DNA were probed using Fe. EDTA affinity cleavage. The
      results of these orientation studies show that the majority of the energetically
      significant interactions mediated by Arg2 occur in the central region of the mnt
      operator. The RK2, RA2, and RM2 mutations reduce the free energy of operator
      binding by 1.7 kcal/mol, 3.3 kcal/mol, and 4.9 kcal/mol, respectively. Double
      mutant thermodynamic cycle analyses using the RA2, RM2, and operator variants
      also reveal interaction free energies between Arg2 and operator base-pairs 9, 10,
      11, 12 and 13, which in aggregate account for most of the Arg2 contribution to
      operator binding.

PMID- 10966799
TI  - Structure of bacteriophage T4 gene product 11, the interface between the
      baseplate and short tail fibers.
AB  - Bacteriophage T4, like all other viruses, is required to be stable while being
      transmitted from host to host, but also is poised to eject efficiently and
      rapidly its double-stranded DNA genome to initiate infection. The latter is
      coordinated by the recognition of receptors on Escherichia coli cells by the long
      tail fibers and subsequent irreversible attachment by the short tail fibers.
      These fibers are attached to the baseplate, a multi-subunit assembly at the
      distal end of the tail. Recognition and attachment induce a conformational
      transition of the baseplate from a hexagonal to a star-shaped structure. The
      crystal structure of gene product 11 (gp11), a protein that connects the short
      tail fibers to the baseplate, has been determined to 2.0 A resolution using
      multiple wavelength anomalous dispersion with Se. This structure is compared to
      the trimeric structure of gp9, which connects the baseplate with the long tail
      fibers. The structure of gp11 is a trimer with each monomer consisting of 218
      residues folded into three domains. The N-terminal domains form a central,
      trimeric, parallel coiled coil surrounded by the middle "finger" domains. The
      fingers emanate from the carboxy-terminal beta-annulus domain, which, by
      comparison with the T4 whisker "fibritin" protein, is probably responsible for
      trimerization. The events leading from recognition of the host to the ejection of
      viral DNA must be communicated along the assembled trimeric (gp9)(3) attached to
      the long tail fibers via the trimeric baseplate protein (gp10)(3) to the trimeric
      (gp11)(3) and the trimeric short tail fibers.

PMID- 10966800
TI  - Structural basis of carbohydrate recognition by lectin II from Ulex europaeus, a
      protein with a promiscuous carbohydrate-binding site.
AB  - Protein-carbohydrate interactions are the language of choice for inter- cellular
      communication. The legume lectins form a large family of homologous proteins that
      exhibit a wide variety of carbohydrate specificities. The legume lectin family is
      therefore highly suitable as a model system to study the structural principles of
      protein-carbohydrate recognition. Until now, structural data are only available
      for two specificity families: Man/Glc and Gal/GalNAc. No structural data are
      available for any of the fucose or chitobiose specific lectins. The crystal
      structure of Ulex europaeus (UEA-II) is the first of a legume lectin belonging to
      the chitobiose specificity group. The complexes with N-acetylglucosamine,
      galactose and fucosylgalactose show a promiscuous primary binding site capable of
      accommodating both N-acetylglucos amine or galactose in the primary binding site.
      The hydrogen bonding network in these complexes can be considered suboptimal, in
      agreement with the low affinities of these sugars. In the complexes with
      chitobiose, lactose and fucosyllactose this suboptimal hydrogen bonding network
      is compensated by extensive hydrophobic interactions in a Glc/GlcNAc binding
      subsite. UEA-II thus forms the first example of a legume lectin with a
      promiscuous binding site and illustrates the importance of hydrophobic
      interactions in protein-carbohydrate complexes. Together with other known legume
      lectin crystal structures, it shows how different specificities can be grafted
      upon a conserved structural framework.

PMID- 10966801
TI  - NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl
      cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a
      different functionality of the protein.
AB  - The 131-amino acid residue parvulin-like human peptidyl-prolyl cis/trans
      isomerase (PPIase) hPar14 was shown to exhibit sequence similarity to the
      regulator enzyme for cell cycle transitions human hPin1, but specificity for
      catalyzing pSer(Thr)-Pro cis/trans isomerizations was lacking. To determine the
      solution structure of hPar14 the (1)H, (13)C, and (15)N chemical shifts of this
      protein have been assigned using heteronuclear two and three-dimensional NMR
      experiments on unlabeled and uniformly (15)N/(13)C-labeled recombinant protein
      isolated from Escherichia coli cells that overexpress the protein. The chemical
      shift assignments were used to interpret the NOE data, which resulted in a total
      of 1042 NOE restraints. The NOE restraints were used along with 71 dihedral angle
      restraints and 38 hydrogen bonding restraints to produce 50 low-energy
      structures. The hPar14 folds into a betaalpha(3)betaalphabeta(2) structure, and
      contains an unstructured 35-amino acid basic tail N-terminal to the catalytic
      core that replaces the WW domain of hPin1 homologs. The three-dimensional
      structures of hPar14 and the PPIase domain of human hPin1 reveal a high degree of
      conservation. The root-mean-square deviations of the mean atomic coordinates of
      the heavy atoms of the backbone between residues 38 to 45, 50 to 58, 64 to 70, 81
      to 86, 115 to 119 and 122 to 128 of hPar14 were 0.81(+/-0.07) A. The hPar14 model
      structure provides insight into how this class of PPIases may select preferential
      secondary catalytic sites, and also allows identification of a putative DNA
      binding motif in parvulin-like PPIases.

PMID- 10966802
TI  - Temperature-dependent equilibrium between the open and closed conformation of the
      p66 subunit of HIV-1 reverse transcriptase revealed by site-directed spin
      labelling.
AB  - X-ray crystallographic studies of human immunodeficiency virus type 1 reverse
      transcriptase complexed with or without substrates or inhibitors show that the
      heterodimeric enzyme adopts distinct conformations that differ in the orientation
      of the so-called thumb subdomain in the large subunit. Site-directed spin
      labelling of mutated residue positions W24C and K287C is applied here to
      determine the distances between the fingers and thumb subdomains of liganded and
      unliganded RT in solution. The inter-spin distances of a DNA/DNA and a pseudoknot
      RNA complexed reverse transcriptase in solution was found to agree with the
      respective crystal data of the open and closed conformations. For the unliganded
      reverse transcriptase a temperature-dependent equilibrium between these two
      states was observed. The fraction of the closed conformation decreased from 95%
      at 313 K to 65% at 273 K. The spectral separation between the two structures was
      facilitated by the use of a perdeuterated ([15)N]nitroxide methane-thiosulfonate
      spin label.

PMID- 10966803
TI  - Two-state expansion and collapse of a polypeptide.
AB  - The initial phase of folding for many proteins is presumed to be the collapse of
      the polypeptide chain from expanded to compact, but still denatured,
      conformations. Theory and simulations suggest that this collapse may be a two
      state transition, characterized by barrier-crossing kinetics, while the collapse
      of homopolymers is continuous and multi-phasic. We have used a laser temperature
      jump with fluorescence spectroscopy to measure the complete time-course of the
      collapse of denatured cytochrome c with nanosecond time resolution. We find the
      process to be exponential in time and thermally activated, with an apparent
      activation energy approximately 9 k(B)T (after correction for solvent viscosity).
      These results indicate that polypeptide collapse is kinetically a two-state
      transition. Because of the observed free energy barrier, the time scale of
      polypeptide collapse is dramatically slower than is predicted by Langevin models
      for homopolymer collapse.

PMID- 10966804
TI  - Probing structural determinants specifying high thermostability in Bacillus
      licheniformis alpha-amylase.
AB  - Bacillus licheniformis alpha-amylase (BLA) is a starch-degrading enzyme that is
      highly thermostable although it is produced by a rather mesophilic organism. Over
      the last decade, the origin of BLA thermal properties has been extensively
      investigated in both academic and industrial laboratories, yet it is poorly
      understood. Here, we have used structure-based mutagenesis in order to probe the
      role of amino acid residues previously proposed as being important for BLA
      thermostability. Residues involved in salt-bridges, calcium binding or potential
      deamidation processes have been selected and replaced with various amino acids
      using a site-directed mutagenesis method, based on informational suppression. A
      total of 175 amylase variants were created and analysed in vitro. Active amylase
      variants were tested for thermostability by measuring residual activities after
      incubation at high temperature. Out of the 15 target residues, seven (Asp121,
      Asn126, Asp164, Asn192, Asp200, Asp204 and Ala269) were found to be particularly
      intolerant to any amino acid substitutions, some of which lead to very unstable
      mutant enzymes. By contrast, three asparagine residues (Asn172, Asn188 and
      Asn190) could be replaced with amino acid residues that significantly increase
      the thermostability compared to the wild-type enzyme. The highest stabilization
      event resulted from the substitution of phenylalanine in place of asparagine at
      position 190, leading to a sixfold increase of the enzyme's half-life at 80
      degrees C (pH 5.6, 0.1 mM CaCl(2)). These results, combined with those of
      previous mutational analyses, show that the structural determinants contributing
      to the overall thermostability of BLA concentrate in domain B and at its
      interface with the central A domain. This region contains a triadic Ca-Na-Ca
      metal-binding site that appears extremely sensitive to any modification that may
      alter or reinforce the network of electrostatic interactions entrapping the metal
      ions. In particular, a loop spanning from residue 178 to 199, which undergoes
      pronounced conformational changes upon removal of calcium, appears to be the key
      feature for maintaining the enzyme structural integrity. Outside this region,
      most salt-bridges that were destroyed by mutations were found to be dispensable,
      except for an Asp121-Arg127 salt-bridge that contributes to the enhanced
      thermostability of BLA compared to other homologous bacterial alpha-amylases.
      Finally, our studies demonstrate that the natural resistance of BLA against high
      temperature is not optimized and can be enhanced further through various means,
      including the removal of possibly deamidating residues.

PMID- 10966805
TI  - A Bayesian system integrating expression data with sequence patterns for
      localizing proteins: comprehensive application to the yeast genome.
AB  - We develop a probabilistic system for predicting the subcellular localization of
      proteins and estimating the relative population of the various compartments in
      yeast. Our system employs a Bayesian approach, updating a protein's probability
      of being in a compartment, based on a diverse range of 30 features. These range
      from specific motifs (e.g. signal sequences or the HDEL motif) to overall
      properties of a sequence (e.g. surface composition or isoelectric point) to whole
      genome data (e.g. absolute mRNA expression levels or their fluctuations). The
      strength of our approach is the easy integration of many features, particularly
      the whole-genome expression data. We construct a training and testing set of
      approximately 1300 yeast proteins with an experimentally known localization from
      merging, filtering, and standardizing the annotation in the MIPS, Swiss-Prot and
      YPD databases, and we achieve 75 % accuracy on individual protein predictions
      using this dataset. Moreover, we are able to estimate the relative protein
      population of the various compartments without requiring a definite localization
      for every protein. This approach, which is based on an analogy to formalism in
      quantum mechanics, gives better accuracy in determining relative compartment
      populations than that obtained by simply tallying the localization predictions
      for individual proteins (on the yeast proteins with known localization, 92%
      versus 74%). Our training and testing also highlights which of the 30 features
      are informative and which are redundant (19 being particularly useful). After
      developing our system, we apply it to the 4700 yeast proteins with currently
      unknown localization and estimate the relative population of the various
      compartments in the entire yeast genome. An unbiased prior is essential to this
      extrapolated estimate; for this, we use the MIPS localization catalogue, and
      adapt recent results on the localization of yeast proteins obtained by Snyder and
      colleagues using a minitransposon system. Our final localizations for all
      approximately 6000 proteins in the yeast genome are available over the web at:
      http://bioinfo.mbb.yale. edu/genome/localize.

PMID- 10966806
TI  - The mammalian Rab family of small GTPases: definition of family and subfamily
      sequence motifs suggests a mechanism for functional specificity in the Ras
      superfamily.
AB  - The Rab/Ypt/Sec4 family forms the largest branch of the Ras superfamily of
      GTPases, acting as essential regulators of vesicular transport pathways. We used
      the large amount of information in the databases to analyse the mammalian Rab
      family. We defined Rab-conserved sequences that we designate Rab family (RabF)
      motifs using the conserved PM and G motifs as "landmarks". The Rab-specific
      regions were used to identify new Rab proteins in the databases and suggest rules
      for nomenclature. Surprisingly, we find that RabF regions cluster in and around
      switch I and switch II regions, i.e. the regions that change conformation upon
      GDP or GTP binding. This finding suggests that specificity of Rab-effector
      interaction cannot be conferred solely through the switch regions as is usually
      inferred. Instead, we propose a model whereby an effector binds to RabF (switch)
      regions to discriminate between nucleotide-bound states and simultaneously to
      other regions that confer specificity to the interaction, possibly Rab subfamily
      (RabSF) specific regions that we also define here. We discuss structural and
      functional data that support this model and its general applicability to the Ras
      superfamily of proteins.

PMID- 10966807
TI  - Structural consequences of mono-glucosylation of Ha-Ras by Clostridium sordellii
      lethal toxin.
AB  - Mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin at effector
      region threonine 35 has diverse effects on the Ras GTPase cycle, the dominant one
      of which is the inhibition of Ras-Raf coupling, leading to complete blockade of
      Ras downstream signaling. To understand the structural basis of the functional
      consequences of glucosylation, the X-ray crystal structure of glucosylated Ras
      GDP was compared with that of non-modified Ras. Glucosylated Ras exhibits a
      different crystal packing but the overall three-dimensional structure is not
      altered. The glucose group does not affect the conformation of the effector loop.
      Due to steric constraints, the glucose moiety prevents the formation of the GTP
      conformation of the effector loop, which is a prerequisite for binding to the Raf
      kinase. The X-ray crystal data also revealed the alpha-anomeric configuration of
      the bound glucose, indicating that the glucose transfer proceeds under retention
      of the C-1 configuration of the d-alpha-glucose. Therefore, glucosylation
      preserves the inactive conformation of the effector loop independently of the
      nucleotide occupancy, leading to a complete inhibition of downstream signaling of
      Ras.

PMID- 10966808
TI  - The strength of acidic activation domains correlates with their affinity for both
      transcriptional and non-transcriptional proteins.
AB  - Activation domains (ADs) appear to work by making specific protein-protein
      contacts with the transcriptional machinery. However, ADs show no apparent
      sequence conservation, they can be functionally replaced by a number of random
      peptides and unrelated proteins, and their function does not depend on sustaining
      a complex tertiary structure. To gain a broader perspective on the nature of
      interactions between acidic ADs and several of their proposed targets, the in
      vivo strengths of viral, human, yeast, and artificial activation domains were
      determined under physiological conditions, and mutant ADs with increased in vivo
      potencies were selected. The affinities between ADs and proposed targets were
      determined in vitro and all interactions were found to be of low-level affinity
      with dissociation constants above 10(-7)M. However, in vivo potencies of all ADs
      correlated nearly perfectly with their affinities for transcriptional proteins.
      Surprisingly, the weak interactions of the different ADs with at least two non
      transcriptional proteins show the same rank order of binding and AD mutants
      selected for increased in vivo strength also have increased affinities to non
      transcriptional proteins. Based on these results, isolated acidic ADs can bind
      with relatively low-level specificity and affinity to many different proteins and
      the strength of these semi-specific interactions determine the strength of an AD.
      I suggest that ADs expose flexible hydrophobic elements in an aqueous environment
      to contact hydrophobic patches over short distances, shifting specificity of
      activators largely to the DNA colocalization of arrays of ADs and targets.

PMID- 10966809
TI  - In vitro evolution of the hammerhead ribozyme to a purine-specific ribozyme using
      mutagenic PCR with two nucleotide analogues.
AB  - The conventional hammerhead ribozyme cleaves RNA 3' to nucleotide triplets with
      the general formula NUH, where N is any nucleotide, U is uridine and H is any
      nucleotide except guanosine. In order to isolate hammerhead ribozyme sequences
      capable of cleaving 3' to the GUG triplet, we performed a mutagenic selection
      protocol starting with the conventional sequence of an NUH-cleaving ribozyme. The
      22 nucleotides in the core and the stem-loop II region were subjected to
      mutagenic PCR using the two nucleotide analogues 6-(2-deoxy-beta-d-ribofuranosyl)
      3,4-dihydro-8H-pyrimido-[4,5-C)][1, 2] oxazin-7-one and of 8-oxo-2'
      deoxyguanosine. After five repetitions of the selection cycle, several clones
      showed cleavage activity. One sequence, having one deletion, showed at least a 90
      times higher in trans cleavage rate than the starting ribozyme. It cleaved 3' to
      GUG and GUA. The sequence of this ribozyme is essentially identical with that
      obtained previously by selection for AUG cleavage starting with a randomised core
      and stem-loop II region. This identical result of two independent selection
      procedures supports the notion that sequences for NUR cleavage, where R is a
      purine nucleotide, are not compatible with the classical hammerhead structure,
      and that the sequence space for this cleavage specificity is very limited. The
      cleavage of NUR triplets is not restricted to the sequence of the substrate that
      was used for selection but is sequence-independent for in trans cleavage,
      although the sequence context influences the value for the cleavage rate
      somewhat. Analysis of cleavage activities indicates the importance of A at
      position L2.5 in loop II.

PMID- 10966810
TI  - Arrangement of photosystem II supercomplexes in crystalline macrodomains within
      the thylakoid membrane of green plant chloroplasts.
AB  - The chloroplast thylakoid membrane of green plants is organized in stacked grana
      membranes and unstacked stroma membranes. We investigated the structural
      organization of Photosystem II (PSII) in paired grana membrane fragments by
      transmission electron microscopy. The membrane fragments were obtained by a short
      treatment of thylakoid membranes with the mild detergent n-dodecyl-alpha, d
      maltoside and are thought to reflect the grana membranes in a native state. The
      membranes frequently show crystalline macrodomains in which PSII is organized in
      rows spaced by either 26.3 nm (large-spaced crystals) or 23 nm (small-spaced
      crystals). The small-spaced crystals are less common but better ordered. Image
      analysis of the crystals by an aperiodic approach revealed the precise positions
      of the core parts of PSII in the lattices, as well as features of the peripheral
      light-harvesting antenna. Together, they indicate that the so-called C(2)S(2) and
      C(2)S(2)M supercomplexes form the basic motifs of the small-spaced and large
      spaced crystals, respectively. An analysis of a pair of membranes with a well
      ordered large-spaced crystal reveals that many PSII complexes in one layer face
      only light-harvesting complexes (LHCII) in the other layer. The implications of
      this type of organization for the efficient transfer of excitation energy from
      LHCII to PSII and for the stacking of grana membranes are discussed.

PMID- 10966811
TI  - High-density mutagenesis by combined DNA shuffling and phage display to assign
      essential amino acid residues in protein-protein interactions: application to
      study structure-function of plasminogen activation inhibitor 1 (PAI-I).
AB  - The identification of specific amino acid residues involved in protein-protein
      interaction is fundamental to understanding structure-function relationships.
      Supported by mathematical calculations, we designed a high-density mutagenesis
      procedure for the generation of a mutant library of which a limited number of
      random clones would suffice to exactly localize amino acid residues essential for
      a particular protein-protein interaction. This goal was achieved experimentally
      by consecutive cycles of DNA shuffling, under error prone conditions, each
      followed by exposure of the target protein on the surface of phages to screen and
      select for correctly folded, functional mutants. To validate the procedure, human
      plasminogen activator inhibitor 1 (PAI-1) was chosen, because its 3D structure is
      known, many experimental tools are available and it may serve as a model protein
      for structure-function studies of serine proteinases and their inhibitors
      (serpins). After five cycles of DNA shuffling and selection for t-PA binding,
      analysis of 27 randomly picked clones revealed that PAI-1 mutants contained an
      average of 9.1 amino acid substitutions distributed over 114 different positions,
      which were preferentially located at the surface of the protein. This limited
      collection of mutant PAI-1 preparations contained multiple mutants defective in
      binding to three out of four tested anti-PAI-1 monoclonal antibodies. Alignment
      of the nucleotide sequence of defective clones permitted assignment of single
      dominant amino acid residues for binding to each monoclonal antibody. The
      importance of these residues was confirmed by testing the properties of single
      point mutants. From the position of these amino acid residues in the 3D structure
      of PAI-1 and the effects of the corresponding monoclonal antibodies on t-PA-PAI-1
      interaction, conclusions can be drawn with respect to this serpin-serine
      proteinase interaction.

PMID- 10966813
TI  - Specificity in protein-protein interactions: the structural basis for dual
      recognition in endonuclease colicin-immunity protein complexes.
AB  - Bacteria producing endonuclease colicins are protected against their cytotoxic
      activity by virtue of a small immunity protein that binds with high affinity and
      specificity to inactivate the endonuclease. DNase binding by the immunity protein
      occurs through a "dual recognition" mechanism in which conserved residues from
      helix III act as the binding-site anchor, while variable residues from helix II
      define specificity. We now report the 1.7 A crystal structure of the 24.5 kDa
      complex formed between the endonuclease domain of colicin E9 and its cognate
      immunity protein Im9, which provides a molecular rationale for this mechanism.
      Conserved residues of Im9 form a binding-energy hotspot through a combination of
      backbone hydrogen bonds to the endonuclease, many via buried solvent molecules,
      and hydrophobic interactions at the core of the interface, while the specificity
      determining residues interact with corresponding specificity side-chains on the
      enzyme. Comparison between the present structure and that reported recently for
      the colicin E7 endonuclease domain in complex with Im7 highlights how specificity
      is achieved by very different interactions in the two complexes, predominantly
      hydrophobic in nature in the E9-Im9 complex but charged in the E7-Im7 complex. A
      key feature of both complexes is the contact between a conserved tyrosine residue
      from the immunity proteins (Im9 Tyr54) with a specificity residue on the
      endonuclease directing it toward the specificity sites of the immunity protein.
      Remarkably, this tyrosine residue and its neighbour (Im9 Tyr55) are the pivots of
      a 19 degrees rigid-body rotation that relates the positions of Im7 and Im9 in the
      two complexes. This rotation does not affect conserved immunity protein
      interactions with the endonuclease but results in different regions of the
      specificity helix being presented to the enzyme.

PMID- 10966812
TI  - Selection of tumor-specific internalizing human antibodies from phage libraries.
AB  - Antibody internalization into the cell is required for many targeted
      therapeutics, such as immunotoxins, immunoliposomes, antibody-drug conjugates and
      for targeted delivery of genes or viral DNA into cells. To generate directly
      tumor-specific internalizing antibodies, a non-immune single chain Fv (scFv)
      phage antibody library was selected on the breast tumor cell line SKBR3.
      Internalized phage were recovered from within the cell and used for the next
      round of selection. After three rounds of selection, 40 % of clones analyzed
      bound SKBR3 and other tumor cells but did not bind normal human cells. Of the
      internalizing scFv identified, two (F5 and C1) were identified as binding to
      ErbB2, and one (H7) to the transferrin receptor. Both F5 and H7 scFv were
      efficiently endocytosed into SKBR3 cells, both as phage antibodies and as native
      monomeric scFv. Both antibodies were able to induce additional functional effects
      besides triggering endocytosis: F5 scFv induces downstream signaling through the
      ErbB2 receptor and H7 prevents transferrin binding to the transferrin receptor
      and inhibits cell growth. The results demonstrate the feasibility of selecting
      internalizing receptor-specific antibodies directly from phage libraries by
      panning on cells. Such antibodies can be used to target a variety of molecules
      into the cell to achieve a therapeutic effect. Furthermore, in some instances
      endocytosis serves as a surrogate marker for other therapeutic biologic effects,
      such as growth inhibition. Thus, a subset of selected antibodies will have a
      direct therapeutic effect.

PMID- 10966814
TI  - Endostatins derived from collagens XV and XVIII differ in structural and binding
      properties, tissue distribution and anti-angiogenic activity.
AB  - Endostatin is a fragment of the C-terminal domain NC1 of collagen XVIII that
      inhibits angiogenesis and tumor growth. We report the characterization of a
      collagen XV endostatin analogue and its parent NC1 domain, obtained by
      recombinant expression in mammalian cells. Both NC1 domains contain a
      trimerization domain, a hinge region that is more sensitive to proteolysis in
      collagen XVIII and the endostatin domain. Unlike endostatin-XVIII, endostatin-XV
      does not bind zinc or heparin, which is explained by the crystal structure of
      endostatin-XV. The collagen XV and XVIII fragments inhibited chorioallantoic
      membrane angiogenesis induced by basic fibroblast growth factor (FGF-2) or
      vascular endothelial growth factor (VEGF), but there are striking differences
      depending on which cytokine is used and whether free endostatins or NC1 domains
      are applied. The collagen XV and XVIII fragments showed a similar binding
      repertoire for extracellular matrix proteins. Differences were found in the
      immunohistological localization in vessel walls and basement membrane zones.
      Together, these data indentify endostatin-XV as an angiogenesis inhibitor, which
      differs from endostatin-XVIII in several important functional details.

PMID- 10966816
TI  - How does a symmetric dimer recognize an asymmetric substrate? A substrate complex
      of HIV-1 protease.
AB  - The crystal structure of an actual HIV-1 protease-substrate complex is presented
      at 2.0 A resolution (R-value of 19.7 % (R(free) 23.3 %)) between an inactive
      variant (D25N) of HIV-1 protease and a long substrate peptide, Lys-Ala-Arg-Val
      Leu-Ala-Glu-Ala-Met-Ser, which covers a full binding epitope of capsid(CA)-p2,
      cleavage site. The substrate peptide is asymmetric in both size and charge
      distribution. To accommodate this asymmetry the two protease monomers adopt
      different conformations burying a total of 1038 A(2) of surface area at the
      protease-substrate interface. The specificity for the CA-p2 substrate peptide is
      mainly hydrophobic, as most of the hydrogen bonds are made with the backbone of
      the peptide substrate. Two water molecules bridge the two monomers through the
      loops Gly49-Gly52 (Gly49'-Gly52') and Pro79'-Val82' (Pro79-Val82). When other
      complexes are compared, the mobility of these loops is correlated with the
      content of the P1 and P1' sites. Interdependence of the conformational changes
      allows the protease to exhibit its wide range of substrate specificity.

PMID- 10966815
TI  - Staggered molecular packing in crystals of a collagen-like peptide with a single
      charged pair.
AB  - The crystal structure of the triple-helical peptide, (Pro-Hyp-Gly)(4)-Glu-Lys-Gly
      (Pro-Hyp-Gly)(5) has been determined to 1.75 A resolution. This peptide was
      designed to examine the effect of a pair of adjacent, oppositely charged residues
      on collagen triple-helical conformation and intermolecular interactions. The
      molecular conformation (a 7(5) triple helix) and hydrogen bonding schemes are
      similar to those previously reported for collagen triple helices and provides a
      second instance of water mediated N--H . . . O==C interchain hydrogen bonds for
      the amide group of the residue following Gly. Although stereochemically capable
      of forming intramolecular or intermolecular ion pairs, the lysine and glutamic
      acid side-chains instead display direct interactions with carbonyl groups and
      hydroxyproline hydroxyl groups or interactions mediated by water molecules.
      Solution studies on the EKG peptide indicate stabilization at neutral pH values,
      where both Glu and Lys are ionized, but suggest that this occurs because of the
      effects of ionization on the individual residues, rather than ion pair formation.
      The EKG structure suggests a molecular mechanism for such stabilization through
      indirect hydrogen bonding. The molecular packing in the crystal includes an axial
      stagger between molecules, reminiscent of that observed in D-periodic collagen
      fibrils. The presence of a Glu-Lys-Gly triplet in the middle of the sequence
      appears to mediate this staggered molecular packing through its indirect water
      mediated interactions with backbone C==O groups and side chains.

PMID- 10966818
TI  - The 1.0 A crystal structure of Ca(2+)-bound calmodulin: an analysis of disorder
      and implications for functionally relevant plasticity.
AB  - Calmodulin (CaM) is a highly conserved 17 kDa eukaryotic protein that can bind
      specifically to over 100 protein targets in response to a Ca(2+) signal. Ca(2+)
      CaM requires a considerable degree of structural plasticity to accomplish this
      physiological role; however, the nature and extent of this plasticity remain
      poorly characterized. Here, we present the 1.0 A crystal structure of Paramecium
      tetraurelia Ca(2+)-CaM, including 36 discretely disordered residues and a fifth
      Ca(2+) that mediates a crystal contact. The 36 discretely disordered residues are
      located primarily in the central helix and the two hydrophobic binding pockets,
      and reveal correlated side-chain disorder that may assist target-specific
      deformation of the binding pockets. Evidence of domain displacements and discrete
      backbone disorder is provided by translation-libration-screw (TLS) analysis and
      multiconformer models of protein disorder, respectively. In total, the evidence
      for disorder at every accessible length-scale in Ca(2+)-CaM suggests that the
      protein occupies a large number of hierarchically arranged conformational
      substates in the crystalline environment and may sample a quasi-continuous
      spectrum of conformations in solution. Therefore, we propose that the
      functionally distinct forms of CaM are less structurally distinct than previously
      believed, and that the different activities of CaM in response to Ca(2+) may
      result primarily from Ca(2+)-mediated alterations in the dynamics of the protein.

PMID- 10966817
TI  - The effect of intracellular molybdenum in Hydrogenophaga pseudoflava on the
      crystallographic structure of the seleno-molybdo-iron-sulfur flavoenzyme carbon
      monoxide dehydrogenase.
AB  - Crystal structures of carbon monoxide dehydrogenase (CODH), a seleno-molybdo-iron
      sulfur flavoprotein from the aerobic carbon monoxide utilizing carboxidotrophic
      eubacterium Hydrogenophaga pseudoflava, have been determined from the enzyme
      synthesized at high (Mo(plus) CODH) and low intracellular molybdenum content
      (Mo(minus) CODH) at 2.25 A and 2.35 A resolution, respectively. The structures
      were solved by Patterson search methods utilizing the enzyme from Oligotropha
      carboxidovorans as the initial model. The CODHs from both sources are
      structurally very much conserved and show the same overall fold, architecture and
      arrangements of the molybdopterin-cytosine dinucleotide-type of molybdenum
      cofactor, the type I and type II [2Fe-2S] clusters and the flavin-adenine
      dinucleotide. Unlike the CODH from O. carboxidovorans, the enzyme from H.
      pseudoflava reveals a unique post-translationally modified C(gamma)-hydroxy
      Arg384 residue which precedes the catalytically essential S-selanyl-Cys385 in the
      active-site loop. In addition, the Trp193 which shields the isoalloxazine ring of
      the flavin-adenine dinucleotide in the M subunit of the H. pseudoflava CODH is a
      Tyr193 in the O. carboxidovorans CODH. The hydrogen bonding interaction pattern
      of the molybdenum cofactor involves 27 hydrogen bonds with the surrounding
      protein. Of these, eight are with the cytosine moiety, eight with the
      pyrophosphate, six with the pyranopterin, and five with the ligands of the Mo
      ion. The structure of the catalytically inactive Mo(minus) CODH indicates that an
      intracellular Mo-deficiency affects exclusively the active site of the enzyme as
      an incomplete non-functional molybdenum cofactor was synthesized. The 5'-CDP
      residue was present in Mo(minus) CODH, whereas the Mo-pyranopterin moiety was
      absent. In Mo(plus) CODH the selenium faces the Mo ion and flips away from the Mo
      site in Mo(minus) CODH. The different side-chain conformations of the active-site
      residues S-selanyl-Cys385 and Glu757 in Mo(plus) and Mo(minus) CODH indicate a
      side-chain flexibility and a function of the Mo ion in the proper orientation of
      both residues.

PMID- 10966819
TI  - "Open" structures of MurD: domain movements and structural similarities with
      folylpolyglutamate synthetase.
AB  - UDP-N-acetylmuramoyl-l-alanine:d-glutamate (MurD) ligase catalyses the addition
      of d-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-l-alanine (UMA).
      The crystal structures of Escherichia coli in the substrate-free form and MurD
      complexed with UMA have been determined at 2.4 A and 1.88 A resolution,
      respectively. The MurD structure comprises three domains each of a topology
      reminiscent of nucleotide-binding folds. In the two structures the C-terminal
      domain undergoes a large rigid-body rotation away from the N-terminal and central
      domains. These two "open" structures were compared with the four published
      "closed" structures of MurD. In addition the comparison reveals which regions are
      affected by the binding of UMA, ATP and d-Glu. Also we compare and discuss two
      structurally characterized enzymes which belong to the same ligase superfamily:
      MurD and folylpolyglutamate synthetase (FGS). The analysis allows the
      identification of key residues involved in the reaction mechanism of FGS. The
      determination of the two "open" conformation structures represents a new step
      towards the complete elucidation of the enzymatic mechanism of the MurD ligase.

PMID- 10966820
TI  - Conformational changes during the assembly of factor B from its domains by (1)H
      NMR spectroscopy and molecular modelling: their relevance to the regulation of
      factor B activity.
AB  - Factor B is a key component of the alternative pathway of complement and is
      cleaved by factor D into the Ba and Bb fragments in the presence of activated C3
      (C3b or C3(H(2)O)). The Ba fragment contains three short consensus/complement
      repeat domains, while the Bb fragment contains a von Willebrand factor type A
      (vWF-A) domain and a serine protease (SP) domain, all three of which are
      implicated in multisite contacts with C3. The upfield-shifted signals in the (1)H
      NMR spectra of factor B, the Ba and Bb fragments, and the vWF-A and SP domains
      were used as sensitive conformational probes of their structures. Temperature
      studies and pH titrations showed that the Ba fragment and the vWF-A and SP
      domains had conformationally mobile structures. The comparison of the NMR spectra
      of the SP domains of both factor B and factor D showed that the factor D
      linewidths were broader than those for factor B, which may result from a range of
      proteolytically inactive conformations of factor D in the absence of substrate.
      The NMR spectra from the separate vWF-A and SP domains in combination with that
      of the Ba fragment generally accounted for that of intact factor B, apart from
      the perturbation of an upfield-shifted signal from the Ba fragment. A new upfield
      shifted signal was observed in the Bb fragment that was not detected in the
      spectra for the vWF-A or SP domains or intact factor B. Ring current calculations
      based on homology models or crystal structures predicted that buried hydrophobic
      methyl-aromatic interactions probably accounted for the upfield-shifted signals,
      with many arising from the N-terminal subdomain of the SP domain to which the C
      terminus of the vWF-A domain is directly linked. It was concluded that: (1) the
      conformation of the free SP domain is better ordered in solution than that of
      factor D; (2) the conformation of the Ba fragment is affected by its
      incorporation into factor B; and (3) the proximity of the vWF-A and SP domains
      within the Bb fragment leads to a conformational change in which conserved
      charged residues may be important. Allosteric structural rearrangements in the SP
      domain as the result of its interactions with the vWF-A domain or the Ba fragment
      provide an explanation of the regulation of the catalytic activity of factor B.

PMID- 10966821
TI  - Conformational changes in serpins: II. The mechanism of activation of
      antithrombin by heparin.
AB  - Antithrombin, uniquely among plasma serpins acting as proteinase inhibitors in
      the control of the blood coagulation cascade, circulates in a relatively inactive
      form. Its activation by heparin, and specifically by a pentasaccharide core of
      heparin, has been shown to involve release of the peptide loop containing the
      reactive centre from partial insertion in the A sheet of the molecule. Here we
      compare the structures of the circulating inactive form of antithrombin with the
      activated structure in complex with heparin pentasaccharide. We show that the
      rearrangement of the reactive centre loop that occurs upon activation is part of
      a widespread conformational change involving a realignment of the two major
      domains of the molecule. We also examine natural mutants that possess high
      affinity for heparin pentasaccharide, and relate the kinetics of their
      interaction with heparin pentasaccharide to the structural transitions occuring
      in the activation process.

PMID- 10966822
TI  - Formation of hydrogen bonds precedes the rate-limiting formation of persistent
      structure in the folding of ACBP.
AB  - A burst phase in the early folding of the four-helix two-state folder protein
      acyl-coenzyme A binding protein (ACBP) has been detected using quenched-flow in
      combination with site-specific NMR-detected hydrogen exchange. Several of the
      burst phase structures coincide with a structure consisting of eight conserved
      hydrophobic residues at the interface between the two N and C-terminal helices.
      Previous mutation studies have shown that the formation of this structure is rate
      limiting for the final folding of ACBP. The burst phase structures observed in
      ACBP are different from the previously reported collapsed types of burst phase
      intermediates observed in the folding of other proteins.

PMID- 10966823
TI  - Abnormalities of calcium cycling in the hypertrophied and failing heart.
AB  - Progressive deterioration of cardiac contractility is a central feature of
      congestive heart failure (CHF) in humans. In this report we review those studies
      that have addressed the idea that alterations of intracellular calcium (Ca(2+))
      regulation is primarily responsible for the depressed contractility of the
      failing heart. The review points out that Ca(2+)transients and contraction are
      similar in non-failing and failing myocytes at very slow frequencies of
      stimulation (and other low stress environments). Faster pacing rates, high
      Ca(2+)and beta-adrenergic stimulation reveal large reductions in contractile
      reserve in failing myocytes. The underlying cellular basis of these defects is
      then considered. Studies showing changes in the abundance of L-type
      Ca(2+)channels, Ca(2+)transport proteins [sarcoplasmic reticulum Ca(2+)ATPase
      (SERCA2), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX)] and Ca(2+) release
      channels (RYR) in excitation-contraction coupling and Ca(2+)release and uptake by
      the sarcoplasmic reticulum (SR) are reviewed. These observations support our
      hypotheses that (i) defective Ca(2+)regulation involves multiple molecules and
      processes, not one molecule, (ii) the initiation and progression of CHF inolves
      defective Ca(2+)regulation, and (iii) prevention or correction of
      Ca(2+)regulatory defects in the early stages of cardiac diseases can delay or
      prevent the onset of CHF.

PMID- 10966825
TI  - Diabetes-induced myocardial structural changes: role of endothelin-1 and its
      receptors.
AB  - Several metabolic abnormalities may be triggered secondary to hyperglycemia in
      diabetes. Some of these abnormalities may alter expression of vasoactive factors
      in the target organs of diabetic complications. We investigated alterations of
      endothelin-1 (ET-1) and its receptors, ET(A) and ET(B), and associated structural
      changes in the myocardium of streptozotocin-induced diabetic rats after 6 months
      of hyperglycemia. We further assessed the preventive effects of an ET-receptor
      antagonist bosentan on these changes. Compared to the non-diabetic, age- and sex
      matched control animals, diabetic rats showed hyperglycemia, glucosuria, reduced
      body weight gain and elevated glycated Hb levels. Measurement of ET-1, ET(A) and
      ET(B) mRNAs by semiquantitative RT-PCR showed significantly increased mRNA levels
      in the hearts of diabetic rats. Treatment with bosentan failed to reduce ET-1 or
      ET(B) mRNA expression in diabetes, however ET(A) mRNA expression was reduced.
      Immunocytochemically, ET-1 was detected in the cardiomyocytes, endothelium and
      smooth muscle cells of the larger blood vessels and was increased in diabetes.
      Autoradiographic localization of ET-1 receptors, using (125)I-ET-1, showed
      increased binding in the endothelium and myocardium of diabetic animals.
      Histologically, focal fibrous scarring with apoptotic cardiomyocytes, consistent
      with changes secondary to microvascular occlusion, was only present in the
      diabetic rats. In keeping with focal fibrosis, myocardium from diabetic rats
      further showed significantly increased mRNA expression of two extracellular
      matrix protein transcripts, fibronectin and collagen alpha 1(IV) which were
      completely prevented by treatment with bosentan. These data suggest that
      hyperglycemia-induced upregulation of the ET-system in the heart may be important
      in the pathogenesis of cardiac involvement in diabetes.

PMID- 10966824
TI  - Antagonism of the positive dromotropic effect of isoproterenol by adenosine: role
      of nitric oxide, cGMP-dependent cAMP-phosphodiesterase and protein kinase G.
AB  - We hypothesized that nitric oxide (NO) plays an important role in mediating the
      anti-adrenergic effect of adenosine on atrioventricular (AV) nodal conduction. In
      guinea-pig hearts instrumented for measurement of AV nodal conduction time
      (atrium-to-His bundle, A-H, interval), the NO synthase (NOS) inhibitor, l-NMMA
      (100 microm), reversibly inhibited 80% (P=0.009, n=6) of adenosine's anti
      adrenergic action on the positive dromotropic effect of isoproterenol (0.01
      microm). In parallel studies carried out in rabbit AV nodal myocytes,
      intracellular mechanisms whereby NO mediates the inhibitory effect of adenosine
      on isoproterenol-induced A-H interval shortening were studied. Adenosine (3
      microm) inhibited isoproterenol-stimulated (0.1 microm) I(Ca,L)(beta -I(Ca,L)) by
      46+/-6% (P<0.001, n=17). Consistent with isolated heart data, the NOS inhibitors,
      l -NMMA (100 microm) and L-NNA (500 microm) attenuated the effect of adenosine on
      beta -I(Ca,L)by 69+/-8% (P<0.001, n=16) and 69+/-7% (P<0.001, n=10),
      respectively. An inhibitor of NO-stimulated guanylyl cyclase LY83538 (40 microm)
      reduced the inhibitory effect of adenosine on beta -I(Ca,L)by 97+/-6% (P=0.004,
      n=15). Similarly, the non-specific inhibitor of cAMP-phosphodiesterases IBMX (50
      microm) decreased the anti-adrenergic effect of adenosine by 60% (P=0.02, n=6),
      whereas the extracellular application of the non-hydrolyzeable cAMP analog 8-Br
      cAMP (500 microm) prevented this action of adenosine. Activation of cGMP
      dependent protein kinase (PKG) by CPT-cGMP (300 microm) diminished beta -I(Ca,L),
      but to a significantly smaller degree (16+/-4%, P=0.025, n=12) than that caused
      by adenosine. NO mediates the anti-adrenergic effect of adenosine on AV nodal
      conduction by a mechanism predominately involving activation of cGMP-dependent
      cAMP-phosphodiesterase and to a lesser extent activation of PKG.

PMID- 10966827
TI  - Enhanced contractile responsiveness to cytosolic Ca(2+) by delta-2 opioid agonist
      deltorphin in intact guinea pig hearts.
AB  - Opioid receptor subtypes, delta and kappa, are found in cardiac tissue and may
      play a role in cardiac function. We explored if the synthetic opioid delta(2)[D
      Ala(2)]-deltorphin (DTP) and mu peptide agonist [D-Ala(2)]-enkephalin (DAMGO)
      alter the left ventricular pressure (LVP) [Ca(2+)](i) relationship in isolated
      guinea pig hearts. LV phasic [Ca(2+)](i) was measured from dual fluorescence
      signals using indo 1. Ca(2+) transients were corrected and calibrated to nM
      [Ca(2+)](i). Diastolic (d), systolic (s) [Ca(2+)](i), and s-d[Ca(2+)](i) were
      plotted v LVP at 0.3 to 6.8 mM [CaCl(2)](e)to assess the association of
      contractility to Ca(2+). Also given were naltriben (NTB) and CTOP, delta(2) and
      mu antagonists, and nifedipine (NIF) and thapsigargin (THAP). From a control of
      880+/-95 nM (SEM), DTP decreased s-d[Ca(2+)](max) to 525+/-82 nM after DTP and to
      405+/-84 nM after NIF, whereas THAP increased s-d[Ca(2+)](max)to 1605+/-275 nM.
      NTB, 795+/-33 nM, NTB+DTP, 820+/-98 nM, DAMGO, 970+/-82 nM, and DAMGO+CTOP, 830+/
      93 nM, gave values similar to controls. From a control value of 61+/-4 mm Hg,
      LVP(max)was increased by DTP to 73+/-3 mmHg and by THAP to 77+/-2 mmHg, was
      unchanged by DAMGO at 48+/-6 mmHg, and was decreased by NIF to 24+/-2 mmHg.
      Compared to the control value of 594+/-18 nM, less s-d[Ca(2+)](i) was required to
      attain 50% s-dLVP(max)(curve left shift) with increasing [CaCl(2)](e) for DTP,
      407+/-17 nM, and more was required for THAP, 737+/-35 nM. DTP raised the slope
      max of s-dLVP(max)(100%) v. s-d[Ca(2+)](i)by 2.7-fold. This indicates DTP
      enhances cardiac performance by enhancing responsiveness to cytosolic
      Ca(2+)rather than by raising diastolic Ca(2+) and subsequently released Ca(2+),
      as does THAP.

PMID- 10966826
TI  - Effect of pressure overload on angiotensin receptor expression in the rat heart
      during early postnatal life.
AB  - The development of cardiac hypertrophy during neonatal life and in adults implies
      different processes. The angiotensin II (Ang II) system is involved in the
      development of cardiac hypertrophy in adults, but its role in neonates remains
      unclear. The aim of this study was to estimate the influence of increased
      hemodynamic load on the developmental pattern of the AT1/AT2 receptor expression
      in the heart. Two-day-old rats submitted to abdominal aortic constriction (AC) or
      sham operation were sacrificed 2 h, and 1, 3, and 8 days after surgery. Ang II
      was evaluated in sera and immunohistology was performed to define the cardiac
      hypertrophy process. The Ang II receptor subtypes 1 and 2 were quantified at the
      receptor and mRNA levels by(125)I-Ang II binding and RT-PCR, respectively. Ang II
      content in sera increased transiently 2 h after surgery in the AC group. In sham
      operated, AT1 and AT2 decreased throughout the period studied at both mRNA and
      receptor levels. However, the AT1 mRNA level decrease was more pronounced than
      that of AT2 (by 57% and 27%, respectively). AC not only prevented the postnatal
      decrease in AT mRNA level but resulted in an increase in AT1 mRNA 8 days after
      surgery (P<0.05). Besides in the AC groups, AT2 mRNA levels but not those of AT1
      mRNA were linearly correlated with the left ventricular mass. At the receptor
      level, a significant transient (1 day after surgery) increase in both AT1 and AT2
      was observed. In conclusion, our data demonstrated that imposition of pressure
      overload soon after birth altered the pattern of AT receptor expression.

PMID- 10966828
TI  - Age- and sex-associated changes in cardiac beta(1)-adrenoceptors from the
      muscular dystrophy (mdx) mouse.
AB  - Variations in beta(1)-adrenoceptor function due to age or sex were examined in
      the mouse model of Duchenne muscular dystrophy. Positive chronotropic and
      inotropic responses to (-)-isoprenaline and antagonist effects of CGP20712A were
      determined in isolated right and left atria from young (12 week) and old (12
      month) male and old (12 month) female mdx mice and their age- and sex-matched
      C57BL/10ScSn (C57) mice. There was no difference in efficacy to (-)-isoprenaline
      when expressed as an increase in the rate of contraction or force of contraction
      as a percentage of Ca(2+)-induced increase respectively in right or left atria
      from age- and sex-matched mdx and C57. Old mdx males showed a decreased
      sensitivity to (-)-isoprenaline (P<0.05) and a reduced affinity to CGP 20712A
      (P<0.05) in both right and left atria compared with old C57 males. These same
      changes were also observed in left atria between old and young mdx males. A
      reduced efficacy to (-)-isoprenaline was also evident when young and old mdx
      males were compared. In contrast, in old females, mdx showed an increased
      affinity to CGP20712A in left and right atria (P<0.05), and an enhanced
      sensitivity to (-)-isoprenaline in right atria. Finally, in left atria, the
      maximum Ca(2+)-induced increase in force of contraction was lower in all mdx
      compared to their age- and sex-matched C57 (P<0.05). In conclusion, age- and sex
      associated changes in beta(1)-adrenoceptor function and responses to calcium were
      demonstrated in cardiac muscle from mdx mice, with a marked deterioration in
      beta(1)-adrenoceptor function occurring with aging in male mdx being particularly
      evident.

PMID- 10966829
TI  - Glutathione protects against myocardial ischemia-reperfusion injury by
      detoxifying peroxynitrite.
AB  - Peroxynitrite (ONOO(-)) formation during acute reperfusion of the ischemic heart
      contributes to the poor recovery of mechanical function. As glutathione (GSH)
      detoxifies ONOO(-), we studied whether it could protect isolated rat hearts
      subjected to exogenous ONOO(-)or to ischemia-reperfusion. We showed that GSH (300
      microm, n=5) abolished the detrimental effect of ONOO(-)(80 microm, n=5) on
      mechanical function of aerobically perfused hearts. Hearts were subjected to 25
      min aerobic perfusion, 20 min global, no-flow ischemia and 30 min reperfusion.
      GSH (3-300 microm, n=7-12) or saline vehicle (control, n=22) were infused for 10
      min prior to ischemia and throughout reperfusion. During reperfusion, GSH caused
      a concentration-dependent improvement in the recovery of mechanical function,
      which was not associated with significant changes in the intracellular
      concentration of GSH. The concentration of dityrosine (a marker of ONOO(-)
      formation) in the coronary effluent during reperfusion was significantly reduced
      in GSH-treated hearts. The concentration of myocardial cGMP was significantly
      elevated by GSH during ischemia and early reperfusion. GSH improves the recovery
      of myocardial mechanical function after ischemia-reperfusion, an effect which may
      be related to the detoxification of ONOO(-)by GSH and the stimulation of soluble
      guanylate cyclase.

PMID- 10966830
TI  - Expression of active alpha(1B)-adrenergic receptors in the heart does not
      alleviate ischemic reperfusion injury.
AB  - Ischemic preconditioning reduces infarct size and improves cardiac function in
      various species, including mice. The mechanism for ischemic preconditioning
      protection is not entirely clear and activation of alpha(1B)-adrenergic receptors
      (AR) is believed to be involved. Transgenic mice expressing constitutively active
      mutant alpha(1B)-AR in the heart have enhanced alpha(1B)-AR activity and
      therefore can be used to test the role of alpha(1B)-AR in ischemic
      preconditioning. Wild-type and transgenic mice were subjected to 30- or 40-min
      periods of left coronary artery occlusion followed by 60-min reperfusion, or
      ischemic preconditioning prior to sustained ischemia-reperfusion. Risk and
      infarct zones were determined by staining with Evans blue and
      triphenyltetrazolium, respectively, and quantitated digitally. Infarct zone and
      infarct size were not different between wild-type and transgenic mice, nor was
      the extent of reduction in infarct size by preconditioning ischemia (wild-type
      mice: 45+/-3 to 18+/-3%, transgenic mice: 46+/-3 to 19+/-2% of the left
      ventricle, both P<0.01). Ventricular function was similar between wild-type and
      transgenic mice with or without ischemia-reperfusion injury. In conclusion,
      enhanced alpha(1B)-AR activity by cardiac-specific expression of constitutively
      active mutant alpha(1B)-AR in mice does not mimic ischemic preconditioning to
      protect against ischemia-reperfusion injury.

PMID- 10966831
TI  - Inherited and de novo mutations in the cardiac actin gene cause hypertrophic
      cardiomyopathy.
AB  - Mutations in genes encoding sarcomeric proteins cause hypertrophic cardiomyopathy
      (HCM). The sarcomeric protein actin plays a central, dual role in cardiac
      myocytes, generating contractile force by interacting with myosin and also
      transmitting force within and between cells. Two missense mutations in the
      cardiac actin gene (ACTC), postulated to impair force transmission, have been
      associated with familial dilated cardiomyopathy (DCM). Recently, a missense
      mutation in ACTC was found to cosegregate with familial HCM. To further test the
      hypothesis that mutations within functionally distinct domains of ACTC cause
      either DCM or HCM, we performed mutational analyses in 368 unrelated patients
      with familial or sporadic HCM. Single strand conformation polymorphism and
      sequence analyses of genomic DNA were performed. De novo mutations in ACTC were
      identified in two patients with sporadic HCM who presented with syncope in early
      childhood. Patients were heterozygous for missense mutations resulting in
      Pro164Ala and Ala331Pro amino acid substitutions, adjacent to regions of actin
      actin and actin-myosin interaction, respectively. A mutation that cosegregated
      with familial HCM was also found, causing a Glu99Lys substitution in a weak
      actomyosin binding domain. The cardiac phenotype in many affected patients was
      characterized by an apical form of HCM. These findings support the hypothesis
      that a single amino acid substitution in actin causes either congestive heart
      failure or maladaptive cardiac hypertrophy, depending on its effect on actin
      structure and function.

PMID- 10966832
TI  - Norepinephrine concentrations in the epicardial transudate reflect early changes
      in adrenergic activity in the isolated perfused heart.
AB  - The aim of this study was to establish whether epicardial transudates could be
      used to uncover small, but physiologically important changes in interstitial NE
      concentrations under normal and pathological conditions. Norepinephrine (NE)
      concentrations measured in epicardial transudate fluid were compared to NE levels
      in the coronary effluent in normal and pressure overload hypertrophied (POH) rat
      hearts. Hearts were isolated together with the stellate ganglion and perfused in
      the inverted position. Epicardial surface transudates, representative fluid of
      the interstitial myocardial compartment, and coronary effluents were collected
      for determination of NE levels in the presence and absence of stellate ganglion
      stimulation. The same protocol was repeated in the presence and absence of
      nisoxetine, a NE uptake blocker. NE concentrations in epicardial transudates were
      16- and 19-fold higher than in the coronary effluent in both sham and POH groups,
      respectively. NE concentrations in the transudates but not in the coronary
      effluents were significantly higher (1.6-fold) in hearts with POH when compared
      to normal hearts. Likewise, nisoxetine (10(-5)m) increased (1.3-fold) NE
      concentrations in the transudates but not in the effluents of sham animals. As
      expected, stellate ganglion stimulation increased NE concentrations in both
      transudates and effluents in sham and POH hearts. In conclusion, determination of
      NE concentrations in epicardial transudates represents a simple, rapid and
      sensitive method to detect increases in adrenergic activity in normal and
      abnormal hearts.

PMID- 10966833
TI  - Metabolic control of contractile performance in isolated perfused rat heart.
      Analysis of experimental data by reaction:diffusion mathematical model.
AB  - The intracellular mechanisms of regulation of energy fluxes and respiration in
      contracting heart cells were studied. For this, we investigated the workload
      dependencies of the rate of oxygen consumption and metabolic parameters in
      Langendorff-perfused isolated rat hearts.(31)P NMR spectroscopy was used to study
      the metabolic changes during transition from perfusion with glucose to that with
      pyruvate with and without active creatine kinase system. The experimental results
      showed that transition from perfusion with glucose to that with pyruvate
      increased the phosphocreatine content and stability of its level at increased
      workloads. Inhibition of creatine kinase reaction by 15-min infusion of
      iodoacetamide decreased the maximal developed tension and respiration rates by a
      factor of two.(31)P NMR data were analyzed by a mathematical model of
      compartmentalized energy transfer, which is independent from the restrictions of
      the classical concept of creatine kinase equilibrium. The analysis of
      experimental data by this model shows that metabolic stability-constant levels of
      phosphocreatine, ATP and inorganic phosphate-at increased energy fluxes is an
      inherent property of the compartmentalized system. This explains the observed
      substrate specificity by changes in mitochondrial membrane potential. The
      decreased maximal respiration rate and maximal work output of the heart with
      inhibited creatine kinase is well explained by the rise in myoplasmic ADP
      concentration. This activates the adenylate kinase reaction in the myofibrillar
      space and in the mitochondria to fulfil the energy transfer and signal
      transmission functions, usually performed by creatine kinase. The activity of
      this system, however, is not sufficient to maintain high enough energy fluxes.
      Therefore, there is a kinetic explanation for the decreased maximal respiration
      rate of the heart with inhibited creatine kinase: i.e. a kinetically induced
      switch from an efficient energy transfer pathway (PCr-CK system) to a non
      efficient one (myokinase pathway) within the energy transfer network of the cell
      under conditions of low apparent affinity of mitochondria to ADP in vivo. This
      may result in a significant decrease in the thermodynamic affinity of
      compartmentalized ATPase systems and finally in heart failure.

PMID- 10966834
TI  - Cardiac-specific overexpression of calsequestrin results in left ventricular
      hypertrophy, depressed force-frequency relation and pulsus alternans in vivo.
AB  - Cardiac-specific overexpression of calsequestrin has been shown to result in
      significant decreases in contractile parameters and intracellular
      Ca(2+)transients in vitro. Therefore, the purpose of the present study was to
      determine the effects of calsequestrin overexpression on basal cardiac function
      and the force-frequency relation in vivo. Calsequestrin overexpression mice (CSQ
      OE, n=20) and their isogenic controls (WT) were studied with an integrative
      approach using transthoracic echocardiography, stress-shortening relations, and
      invasive hemodynamics in intact closed-chest mice. M-mode echocardiography
      indicated that calsequestrin overexpression resulted in concentric hypertrophy
      (+52%) and an increase in LV ejection phase indices. However, mean end-systolic
      stress-shortening coordinates revealed that at matched end-systolic wall-stress,
      fractional shortening was depressed in CSQ-OE mice. This was confirmed by
      depressed indices of LV isovolumic contraction and relaxation in CSQ-OE v. WT
      mice. Furthermore, overexpression of calsequestrin resulted in a downward and
      leftward shift of the biphasic force-frequency relation; thus, the critical heart
      (HR(crit)) was significantly lower in calsequestrin-overexpression mice (264+/-15
      bpm) than in wild-type controls (365+/-21 bpm). Surprisingly, calsequestrin
      overexpression was associated with the induction of pulsus alternans in every
      animal (at an average heart rate of 428+/-26 bpm), whereas none of the wild-type
      controls displayed this phenomenon. We conclude that: (i) although increased
      levels of calsequestrin result in decreased myocardial contractility and a
      depressed force-frequency relation, LV wall stress is reduced and chamber
      function is normal, and (ii) an increase in SR Ca(2+)storage capacity induces
      pulsus alternans in the intact anesthetized mouse.

PMID- 10966835
TI  - Vascular beta-adrenergic receptor adenylyl cyclase system in maturation and
      aging.
AB  - The objective of this study was to determine how maturation and aging affects
      beta (beta)-adrenergic receptor (AR) control of arterial vasorelaxation. Left
      ventricular (LV) hemodynamics and arterial vasorelaxation in thoracic artery
      segments were studied in Brown Norway, Fisher 344 cross rats at 6 weeks, 6
      months, and 23 months of age. We defined changes in maturation as occurring
      between 6 weeks and 6 months of age and changes in aging as occurring between 6
      months and 23 months of age. With maturation, isoproterenol resulted in a
      downward shift in heart rate and an upward shift in both LV dP/dt and peripheral
      vascular resistance responses. Similar changes were noted with aging except for
      the downward shift in LV dP/dt isoproterenol response. There was a dose-dependent
      increase in arterial vasorelaxation in response to isoproterenol in all age
      groups, but the 6-week-old animals had a 5-fold (P<0.01) increase in
      vasorelaxation compared to other age groups. The isoproterenol-induced arterial
      vasorelaxation response was not altered by removal of the endothelium. The
      vasodilatory responses to nitroglycerin, acetylcholine, and adenosine were
      diminished (P<0.05) with aging. The vasorelaxation responses to forskolin and
      IBMX were unchanged with maturation and diminished with aging. Incubation of
      arterial rings in cholera toxin resulted in a reduction in relaxation only in
      arteries from 6-week-old rats. Maturation resulted in no change in beta -AR
      density [20.2+/-0.7 v. 18.5+/-0.5 fmol/mg protein, P=n.s., 6 weeks (n=2, 18
      aortas were combined v 6-month-old rats)]. With maturation, there was no change
      in G alpha(i)level. However, beta ARK1 levels were increased (55. 4+/-2.1 v.
      40.8+/-0.4, arbitrary densitometry units) and G alpha(s)levels were decreased
      (29.5+/-0.8 v. 49.9+/-1.9, arbitrary densitometry units). Aging resulted in no
      change in beta -AR density (15.3+/-1.7 v. 18.5+/-0.5 fmol/mg membrane protein),
      but decreases in basal, isoproterenol-, naF-, and forskolin-stimulated AC
      activities. Compared to 6 week data, 23-month-old rats exhibited no change in
      either G alpha(i)or beta ARK1, however, G alpha(s) was decreased. In summary,
      beta -AR-stimulated arterial vasorelaxation is depressed during maturation and
      aging. Since there is no change in beta -AR density but a decrease in G
      alpha(s)and in basal/stimulated AC activities, the defect in beta -AR signaling
      during maturation and aging is probably a post receptor defect, i.e. possibly in
      the receptor-G protein coupling.

PMID- 10966836
TI  - Role of sarcoplasmic reticulum in ischemic preconditioning.

PMID- 10966837
TI  - Re: Preconditioning with ischemia: a delay of lethal cell injury in ischemic
      myocardium.

PMID- 10966838
TI  - Cellular interactions and signaling in cartilage development.
AB  - The long bones of the developing skeleton, such as those of the limb, arise from
      the process of endochondral ossification, where cartilage serves as the initial
      anlage element and is later replaced by bone. One of the earliest events of
      embryonic limb development is cellular condensation, whereby pre-cartilage
      mesenchymal cells aggregate as a result of specific cell-cell interactions, a
      requisite step in the chondrogenic pathway. In this review an extensive
      examination of historical and recent literature pertaining to limb development
      and mesenchymal condensation has been undertaken. Topics reviewed include limb
      initiation and axial induction, mesenchymal condensation and its regulation by
      various adhesion molecules, and regulation of chondrocyte differentiation and
      limb patterning. The complexity of limb development is exemplified by the
      involvement of multiple growth factors and morphogens such as Wnts, transforming
      growth factor-beta and fibroblast growth factors, as well as condensation events
      mediated by both cell-cell (neural cadherin and neural cell adhesion molecule)
      and cell-matrix adhesion (fibronectin, proteoglycans and collagens), as well as
      numerous intracellular signaling pathways transduced by integrins, mitogen
      activated protein kinases, protein kinase C, lipid metabolites and cyclic
      adenosine monophosphate. Furthermore, information pertaining to limb patterning
      and the functional importance of Hox genes and various other signaling molecules
      such as radical fringe, engrailed, Sox-9, and the Hedgehog family is reviewed.
      The exquisite three-dimensional structure of the vertebrate limb represents the
      culmination of these highly orchestrated and strictly regulated events.
      Understanding the development of cartilage should provide insights into
      mechanisms underlying the biology of both normal and pathologic (e.g.
      osteoarthritis) adult cartilage.

PMID- 10966839
TI  - A 5-year randomized controlled, double-blind study of glycosaminoglycan
      polysulphuric acid complex (Rumalon) as a structure modifying therapy in
      osteoarthritis of the hip and knee.
AB  - OBJECTIVE: To determine the structure (disease) modifying effect of a
      glycosaminoglycan polypeptide association complex (GP-C; Rumalon) in patients
      with knee and hip osteoarthritis (OA). METHODS: Double-blind, randomized, placebo
      controlled five-year study. Primary assessment criterion was change in
      radiographic joint space width between baseline and follow-up at 5 years.
      Secondary outcome criteria included Lequesne algofunctional index (LAI), pain on
      passive motion and consumption of non-steroidal antiinflammatory drugs (NSAIDs).
      The patients received 10 courses of injections of placebo or GP-C 2 ml
      intramuscularly in 5 years (two courses each year). Each course included 15
      injections administered twice weekly. RESULTS: There were 277 patients with knee
      OA and 117 patients with hip OA. Control and GP-C treated groups were comparable
      as to sex, age, duration of disease, body weight, X-ray stage and value of LAI at
      the baseline. Knee joint space at 5 years decreased 0.37+/-0.08 (mean+/-standard
      deviation) mm for GP-C and 0.42+/-0.08 mm for placebo groups (P=0.68). Hip joint
      space at 5 years decreased 0.21+/-0.08 mm for GP-C and 0.22+/-0.08 mm for placebo
      groups (P=0.53). In a subset of patients with hip OA, Kellgren-Lawrence> or =2
      and JSW> or =1 mm, there was a trend in favor of GPC for lower joint space
      narrowing in 5 years (P=0.11). In addition, there were no statistical differences
      between the treatment groups in LAI, pain on passive motion and consumption of
      NSAIDs. Side-effects after GP-C (14.5%) were rare, mild and not more frequent
      than in the placebo group (15%). CONCLUSION: We were not able to demonstrate a
      structure modifying effect of GP-C in OA of the hip or knee. Radiographic
      progression of OA in both knee and hip OA was lower than expected in both study
      groups.

PMID- 10966840
TI  - Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low
      molecular weight sodium chondroitin sulfate and manganese ascorbate in the
      management of knee osteoarthritis.
AB  - OBJECTIVES: The objective of this study was to evaluate the oral combination of
      glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate for the
      treatment of osteoarthritis (OA) of the knee. DESIGN: A randomized placebo
      controlled study design was implemented. We recruited 93 patients with OA of the
      knee from a single center. The intervention group received 1000 mg FCHG49
      glucosamine HCl, 800 mg TRH122 low molecular weight sodium chondroitin sulfate
      and 152 mg manganese ascorbate twice daily (Cosamin DS). Patients were evaluated
      initially and then every 2 months for 6 months. The primary outcome was the
      Lesquene Index of severity of osteoarthritis of the knee (ISK). RESULTS: Patients
      with radiographically mild or moderate OA (N=72) in the intervention group showed
      significant improvement in the ISK at 4 and 6 months (P=0.003 and P=0.04,
      respectively). The response rate to the medication was 52% vs a 28% response rate
      to placebo. Patients with radiographically severe osteoarthritis (N=21) did not
      show significant improvements in the ISK. There was a 17% incidence of adverse
      events in the intervention group and 19% in the placebo group. CONCLUSIONS: The
      studied combination of glucosamine HCl, sodium chondroitin sulfate and manganese
      ascorbate was found to be effective for the treatment of radiographically mild to
      moderate OA of the knee as measured by the ISK. This is the first U.S. study of
      these agents.

PMID- 10966841
TI  - Neochondrogenesis in repair of full-thickness articular cartilage defects using
      free autogenous periosteal grafts in the rabbit. A follow-up in six months.
AB  - OBJECTIVE: To analyse the repair of lesions of articular cartilage with
      periosteum-free implants and follow-up at 6 months. DESIGN: Thirty-six New
      Zealand rabbits, 4-6 weeks old, were used. Full-thickness articular cartilage
      defects in the medial femoral condyle were created. Spontaneous evolution
      occurred in 18 animals; the other 18 animals were treated with a free autogenous
      periosteal tibial implant fixed with Tissucol. Animals were killed in groups of
      six at 8, 12 and 24 weeks. Macroscopic, histologic and histochemical results were
      evaluated and analysed statistically using the Mann-Whitney U-test. RESULTS: The
      spontaneous evolution of the lesion did not lead to complete repair in any case.
      The periosteum-free implant provided complete repair of the lesion and
      statistically significant restoration of the articular surface. CONCLUSIONS: In
      the rabbit, this study confirms the incomplete spontaneous repair of articular
      cartilage and the chondrogenic potential of tibial periosteum-free implants, with
      long-term maintenance of the macroscopic, histologic and histochemical
      characteristics of neo-cartilage. This raises the possibility of its use as an
      alternative method in the repair of circumscribed osteochondral lesions in young
      patients.

PMID- 10966842
TI  - The long-term effects of hyaluronan during development of osteoarthritis
      following partial meniscectomy in a rabbit model.
AB  - OBJECTIVE: The long-term effect of hyaluronan (HA) on meniscus remodeling and
      articular cartilage preservation was assessed during the development of
      osteoarthritis following partial meniscectomy in a rabbit model. DESIGN:
      Approximately 60% of the region of each medial meniscus of 20 rabbit knees was
      excised bilaterally. The left knee joint was treated with five weekly
      intraarticular injections of 0.3 ml of HA, beginning 1 week after surgery. The
      right control knee was injected with PBS on the same schedule. Six months after
      surgery, animals were killed and the medial menisci and tibial articular
      cartilage were evaluated morphologically, histologically and biochemically.
      RESULTS: Meniscal regeneration was observed as newly synthesized translucent
      tissue, and image analysis revealed that the amount of this tissue was
      significantly greater in the HA-treated menisci than in the vehicle-treated
      menisci. Safranin-O staining and image analysis revealed the increased presence
      of glycosaminoglycans in the HA-treated menisci relative to vehicle-treated
      menisci while vascularity and biochemical parameters (hydration, total GAGs and
      reducible collagen crosslinks) were statistically similar in HA- and vehicle
      treated menisci. Gross morphologic grading with India ink revealed a trend for
      less deterioration of tibial articular cartilage in the HA group (P=0.09) while
      Mankin's score of the HA-treated tibial articular cartilage was marginally lower
      than that of the vehicle group (P=0.06). Biochemical assessments showed a trend
      for higher total GAGs concentration in the HA-treated articular cartilage when
      compared to the vehicle treatment group (P=0.06). CONCLUSION: The present study
      has demonstrated that following partial meniscectomy, treatment with hyaluronan
      can enhance meniscal regeneration and may inhibit articular cartilage
      degeneration as long as six months post surgery.

PMID- 10966843
TI  - Cartilage damage after intraarticular exposure to collagenase 3.
AB  - OBJECTIVE: To determine the in vivo effects of intraarticular MMP-13. METHODS:
      Human recombinant MMP-13 was injected intraarticularly (i.a. ) into the hamster
      knee joint. MMP-13 activity, collagen and proteoglycan fragments, and hyaluronan
      were measured in synovial fluid. Antibody 9A4 was used to localize collagen
      damage. Western blotting was used to determine the size of type II collagen
      fragments. RESULTS: MMP-13 activity measurements showed greater than 98% of MMP
      13 to be cleared instantly from the joint cavity. The remainder was cleared with
      a t(1/2)of 2 h. Immunohistochemical staining demonstrated collagen cleavage was
      limited to a thin superficial band on the surface of the articular cartilage
      whereas collagen damage extended more deeply into the synovial capsule and the
      menisci. The elevation of proteoglycan and hyaluronan in synovial fluid after MMP
      13 was modest. Collagen fragments appeared in synovial fluid within 15 min
      following MMP-13. They were cleared with a half-life of circa 1.8 h and the
      predominant fragment was 32 kDa. CONCLUSIONS: Activated MMP-13 leads to tissue
      collagen damage with the release of collagen fragments. These fragments are
      measurable and could provide a method for assessment of cartilage collagen
      damage.

PMID- 10966844
TI  - Meniscal ossification in spontaneous osteoarthritis in the guinea-pig.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ossification state of
      the meniscus in the guinea-pig stifle joint using micro-computerized tomography.
      DESIGN: Hind limbs from six (N=12) and 24 (N=11) month-old male Hartley guinea
      pigs were removed and the joints were imaged using high resolution micro
      computerized tomography. The ossified volume of the medial and lateral menisci
      from both groups of animals was quantified. RESULTS: Ossification of both the
      medial and lateral menisci of the both the 6- and 24-month-old animals was
      observed. In both age groups, the ossified region of the medial meniscus was
      significantly larger than the lateral meniscus. In addition, there is a
      significant increase in ossified volume of the medial meniscus between 6 and 24
      months of age. CONCLUSIONS: There is a significant amount of ossification of the
      menisci in the male Hartley guinea-pig, with the medial compartment showing more
      bone than the lateral. In addition, as the animals age, there is an increase in
      ossification within the medial compartment. Bone remodeling and cartilage
      degeneration is evident in the medial compartment within these animals as they
      age. It is possible that the increased ossification of the medial meniscus could
      alter the joint biomechanics and, in part, stimulate this medial compartment
      joint destruction.

PMID- 10966845
TI  - Dexamethasone inhibition of TGF beta-induced cell growth and type II collagen
      mRNA expression through ERK-integrated AP-1 activity in cultured rat articular
      chondrocytes.
AB  - Intraarticular injection of dexamethasone (DEX) accelerates cartilage degradation
      due to the suppression of chondrocyte proliferation and extracellular matrix
      formation. The present study first demonstrated the interaction between DEX and
      TGF beta, a potent growth factor for cultured rat articular chondrocytes (CRAC),
      and then investigated the molecular mechanism by which DEX counteracts TGF beta
      induced chondrocyte proliferation and differentiation through the regulation of
      AP-1 activity. DEX reduced serum-deprived and TGF beta-stimulated cell growth and
      [(3)H]-thymidine incorporation of CRAC. DEX also inhibited the expression of
      (alpha)1 type II collagen with concomitant suppression of the promoter activity.
      Transfection studies using a reporter vector with AP-1 responsive elements showed
      that DEX reduced TGF beta-activated but not basal luciferase activities.
      Activation of 3TP-luc, another AP-1 responsive element containing reporter was
      also blocked by DEX. GAL4-Elk1 studies revealed that DEX suppressed TGF beta
      induced ERK activation which led to c-fos gene expression followed by increase in
      AP-1 complex formation, whereas the Smad pathway was not involved in DEX
      dependent negative regulation of AP-1 in a reporter assay that requires FAST1
      Smad2 for the activation. DEX also eliminated TGF beta-induced c-fos mRNA
      expression and ERK activation in Northern analysis and in vitro kinase assay,
      respectively. Further, DNA synthesis and transactivation of type II collagen by
      TGF beta were inhibited by PD98059, an inhibitor of MEK. Our results indicate
      that DEX suppressed TGF beta-induced chondrocyte proliferation and type II
      collagen expression, probably through selective inhibition of ERK integrated AP-1
      activation.

PMID- 10966847
TI  - Re: Usegi M, Jasin HE. Macromolecular transport across the superficial layer of
      articular cartilage. Osteoarthritis Cart 2000;8:13-6.

PMID- 10966846
TI  - Bovine articular chondrocyte function in vitro depends upon oxygen tension.
AB  - Articular cartilage is a physiologically hypoxic tissue with a proposed gradient
      of oxygen tension ranging from about 10% oxygen at the cartilage surface to less
      than 1% in the deepest layers. The position of the chondrocyte within this
      gradient may modulate the cell's behavior and phenotype. Moreover, the oxygen
      gradient is likely to be disturbed during joint diseases in which the pO(2)of the
      synovial fluid declines which may cause changes in chondrocyte behavior and gene
      expression. Thus, there is a need to understand the chondrocyte's response to
      different oxygen tensions. We compared the behavior of bovine articular
      chondrocytes cultured in alginate beads for 7 days in medium maintained at <0.1,
      5, 10 or 20% oxygen. The chondrocytes' survival, differentiation, cell division,
      viability and matrix production were assessed at each oxygen tension and rRNA and
      mRNA abundance was measured. Chondrocytes were able to survive under all oxygen
      tensions for at least 7 days but cells cultured under anoxic conditions were
      metabolically less active than cells maintained in higher oxygen tensions; this
      was associated with a decrease in matrix production. In <0.1% oxygen there was a
      marked decrease in rRNA and mRNA abundance in the cells. There were no
      differences in cell division or differentiation between any oxygen tensions.
      These findings indicate that articular chondrocytes can be cultured successfully
      in the pO(2)range in which they are thought to exist in vivo (5-10% pO(2)) and
      are fully active under these conditions. Under anoxic conditions (<0.1% pO(2))
      function is severely compromised.

PMID- 10966848
TI  - The biology of inherited cancer.
AB  - This issue of Cancer Biology is focused on inherited cancer. In this short
      introduction to the topic we give a brief overview and list genes and the
      corresponding inherited cancer syndromes. We discuss the basic mechanisms of
      inherited cancer and the clinical implication of predictive genetic testing for
      cancer.

PMID- 10966849
TI  - Retinoblastoma: the disease, gene and protein provide critical leads to
      understand cancer.
AB  - Retinoblastoma has contributed much to the understanding of cancer. The protein
      product of the RB gene, pRB, is a multifaceted regulator of transcription which
      controls the cell cycle, differentiation and apoptosis in normal development of
      specific tissues. Elucidating the mechanisms in which pRB plays a critical role
      will enable novel therapies and strategies for prevention, not only for
      retinoblastoma, but for cancer in general.

PMID- 10966850
TI  - Hereditary breast cancer: a review.
AB  - Breast cancer is the most common female malignancy and a major cause of death in
      middle-aged women. A positive family history of breast cancer is one of the
      strongest risk factors for the disease. In addition, many afflicted breast cancer
      families are characterized by early onset and bilateral tumors, and also, in some
      cases, associated malignancies, most commonly ovarian cancer. It is estimated
      that 5-10% of all breast cancer cases are due to autosomal dominant genes
      segregating with the disease. Mutations in the BRCA1 and BRCA2 genes are known to
      predispose to breast and ovarian cancer in many families. Other genes are only
      involved in very rare syndromes, and additional genes remain to be disclosed.

PMID- 10966851
TI  - Hereditary intestinal cancer.
AB  - Mechanisms involved in hereditary intestinal cancer are likely to play a role in
      sporadic tumorigenesis as well. Studies focusing on the molecular biology
      underlying these syndromes has contributed considerably to our knowledge on
      molecular bases of malignant transformation. It can be concluded, that there are
      two aspects to the importance of studies on intestinal cancer predisposition.
      First, the families suffering from cancer proneness need help which can, to some
      extent, be provided through molecular genetic studies. Second, the resources
      appointed to such research have produced scientific advances with outstanding
      importance to our understanding of common malignant diseases.

PMID- 10966852
TI  - Multiple endocrine neoplasia type 1.
AB  - The recent cloning of the gene responsible for multiple endocrine neoplasia type
      1 (MEN 1) has opened new avenues for both clinical and basic science research in
      the field of endocrine oncology. A large amount of genetic information,
      particularly those in relation to germline and somatic mutations, has since been
      published during the last 2 years. This new knowledge has provided important
      insights into its gene function. The significance of these advances in relation
      to clinical management and future directions for research is discussed.

PMID- 10966853
TI  - Inherited epithelial tumors of the kidney: old and new diseases.
AB  - This review summarizes information on inherited epithelial tumors of the kidney.
      Emphasis is placed on identifying clinically distinct inherited forms of renal
      cancer because each distinct clinical syndrome defines a different renal cancer
      susceptibility gene. So far, two genes that predispose to epithelial cancers of
      the kidney have been identified, VHL and the MET proto-oncogene. Available
      evidence suggests that several renal cancer genes remain to be identified.

PMID- 10966854
TI  - Hereditary cutaneous melanoma.
AB  - Members of some kindreds have a hereditary predisposition for development of
      cutaneous melanoma. Cytogenetic and linkage studies implicated chromosomes 1p and
      9p as possible locations for genetic alterations predisposing for melanoma.
      Germline mutations in the CDKN2A gene on chromosome 9p21 have been identified in
      hereditary melanoma, but are present in only approximately 40% of kindreds with
      linkage to 9p21, indicating that changes in other gene(s) at this location may
      also predispose to melanoma. In a few families, germline mutations in the CDK4
      gene are present. The genetic alterations underlying disease predisposition in a
      large proportion of melanoma families remain unknown.

PMID- 10966855
TI  - Introduction: the molecular cell biology of insulin production

PMID- 10966856
TI  - Regulation of insulin gene transcription.
AB  - Recent studies of the insulin gene promoter and the transcription factors that
      regulate it have expanded our understanding of both how the production of insulin
      is restricted to the pancreatic beta -cell, and how that production is regulated
      by physiologic signals such as glucose. A picture is emerging in which an
      elaborate set of transcription factors binds to specific sequences along the
      promoter and recruits additional transcriptional co-activators to build a
      functional transcriptional activation complex that is unique to beta -cells.
      Surprisingly, however, genetic experiments in mice have demonstrated an
      unexpected degree of redundancy in the factors that control insulin gene
      expression, and have revealed the presence of a network of transcription factors
      that coordinate the expression of factors forming the insulin gene activation
      complex.

PMID- 10966857
TI  - Translational regulation of proinsulin biosynthesis and proinsulin conversion in
      the pancreatic beta-cell.
AB  - Insulin secretion from the pancreatic beta -cell can be initiated in minutes,
      vary as much as 50-100-fold, and be sustained for several hours without need for
      changes in insulin gene transcription. Remarkably, the cellular content of the
      hormone and its molecular composition do not vary appreciably in the face of
      changes of insulin granule exocytosis. Minimal morphological changes are
      apparent, further indicating that the movement of lipids and membrane proteins
      between the granule storage pool, the plasma membrane, and Golgi are likewise
      tightly controlled. Such homeostasis is achieved by an interplay of signaling
      pathways originating from the metabolism of glucose with downstream targets at
      the level of translation of dense-core granule proteins, granule biogenesis, and
      membrane trafficking. Our scant knowledge in this area is confined mostly to a
      descriptive account of the fate of the major secreted components, principally
      insulin and the enzymes PC1, PC2, and CPH involved in the proteolytic conversion
      of proinsulin to insulin. A common theme seems to be the role of intracellular
      energy homeostasis in integrating the stimulus-secretion and stimulus
      biosynthetic responses of this cell.

PMID- 10966858
TI  - Trafficking/sorting and granule biogenesis in the beta-cell.
AB  - Proinsulin is packaged into nascent (immature, clathrin-coated) secretory
      granules in the trans-Golgi network (TGN) of the beta -cell along with other
      granular constituents including the proinsulin conversion enzymes. It is assumed
      that such packaging is dependent on an active sorting process, separating
      granular proteins from other secretory or membrane proteins, but the mechanism
      remains elusive. As granules mature, the clathrin coat is lost, the intragranular
      milieu is progressively acidified, and proinsulin is converted to insulin and C
      peptide. Loss of clathrin is believed to arise by budding of clathrin-coated
      vesicles from maturing granules, carrying with them any inappropriate or
      unnecessary products and providing an additional means for refinement of granular
      content.

PMID- 10966859
TI  - Beta-granule transport and exocytosis.
AB  - Regulated beta -granule exocytosis is critical for the ability of the beta -cell
      to finely control body glucose homeostasis. This is now understood to be a
      multistage process whereby beta -granules are transported from
      biosynthetic/storage sites in the cell cytoplasm and targeted to specific regions
      of the plasma membrane. Exocytosis is achieved when these granules are triggered
      to fuse with the membrane by an elevated cytosolic Ca(2+). Dramatic advances have
      been made recently in our understanding of the protein-protein interactions and
      regulatory signals that govern intracellular transport and fusion. Although best
      understood for exocytosis from neurons and neuroendocrine cells, similar
      processes are thought to be conserved in the beta -cell.

PMID- 10966860
TI  - Metabolic control of beta-cell function.
AB  - Glucose-induced insulin secretion is pulsatile. Glucose metabolism generates
      oscillations in the ATP/ADP ratio which lead to opening and closing of ATP
      sensitive K(+)-channels producing subsequent oscillations in membrane potential,
      cytoplasmic calcium and insulin release. Metabolic signals derived from glucose
      can also stimulate insulin release independent of their effects on ATP-sensitive
      K(+)-channels. The ATP/ADP ratio may mediate both ATP-sensitive K(+)-channel
      dependent and -independent pathways of secretion. Glucose metabolism also results
      in an increase in long-chain acyl-CoA, which is proposed to act as an effector
      molecule in the beta -cell. Long-chain acyl-CoA has a variety of effects in the
      beta -cell that may effect insulin secretion including opening ATP-sensitive K(+)
      channels, activating endoplasmic reticulum Ca(2+)-ATPases and stimulating
      classical protein kinase C activity. In addition to stimulating insulin release,
      nutrients also effect gene expression, protein synthesis and beta -cell
      proliferation. Gene expression is effected by nutrient induction of a variety of
      immediate early response genes. Glucose stimulates proinsulin biosynthesis both
      at the translational and transcriptional level. beta -cell proliferation, as a
      result of insulin-like growth factor and growth hormone mitogenic pathways, is
      also glucose dependent. Thus, many beta -cell functions in addition to secretion
      are controlled by nutrient metabolism.

PMID- 10966861
TI  - Introduction: opening up tight junctions

PMID- 10966862
TI  - Transmembrane proteins of tight junctions.
AB  - Tight junctions from a morphological and functional boundary between the apical
      and basolateral cell surface domains of epithelia and endothelia, and regulate
      selective diffusion along the paracellular space. Two types of four-span
      transmembrane proteins, occludin and claudins, as well as the single-span protein
      JAM are associated with tight junctions. The functional analysis of these
      proteins starts to reveal how they are involved in the functions of tight
      junctions, which of their domains are important for these functions, and how they
      interact with each other to form the junctional diffusion barriers.

PMID- 10966863
TI  - Assembly of tight junctions during early vertebrate development.
AB  - Tight junction formation during development is critical for embryonic patterning
      and organization. We consider mechanisms of junction biogenesis in cleaving mouse
      and Xenopus eggs. Junction assembly follows the establishment of cell polarity at
      8-cell (mouse) or 2-cell (Xenopus) stages, characterized by sequential membrane
      delivery of constituents, coordinated by embryonic (mouse) or maternal (Xenopus)
      expression programmes. Cadherin adhesion is permissive for tight junction
      construction only in the mouse. Occludin post-translational modification and
      membrane delivery, mediated by delayed ZO-1 alpha(+)isoform expression in the
      mouse, provides a mechanism for completion of tight junction biogenesis and
      sealing, regulating the timing of blastocoel cavitation.

PMID- 10966864
TI  - 'Putting the squeeze' on the tight junction: understanding cytoskeletal
      regulation.
AB  - The apical perijunctional actomyosin ring of epithelia is structurally associated
      with the tight junction. The functional association between the tight junction
      and the perijunctional actomyosin ring was initially described in studies using
      pharmacological agents that disrupt microfilaments. More recently, this
      interaction has been studied in physiological, pathophysiological, and molecular
      models of tight junction regulation. These studies have demonstrated the central
      role of actomyosin contraction in tight junction regulation. With the
      identification of novel tight junction proteins and characterization of their
      protein:protein interactions comes the promise of detailed understanding of the
      molecular interactions that mediate tight junction regulation.

PMID- 10966865
TI  - Intercellular junctions: downstream and upstream of Ras?
AB  - Most human tumors are of epithelial origin, and these tumors gradually lose their
      epithelial character in a process termed the epithelial-mesenchymal transition.
      Approximately 40% of human tumors have activating mutations in one of the three
      RAS genes. Given these statistics, it is critically important to understand the
      role of Ras signaling in the epithelial-mesenchymal transition. This review
      considers the mechanisms and effectors through which Ras may regulate
      intercellular junction formation in epithelial cells. Conversely, intercellular
      junction proteins themselves may play a role in regulating Ras activation and
      signaling.

PMID- 10966867
TI  - Adaptations of the archaeal cell membrane to heat stress.
AB  - In extreme environments varying from hot to cold, acidic to alkaline, and highly
      saline, mainly Archaea are found. Thermophilic and extremely acidophilic Archaea
      have a membrane that contains membrane spanning tetraether lipids. These tetra
      ether membranes have a limited permeability for protons even at the high
      temperatures of growth and this property makes it possible for thermophilic
      archaea to maintain a viable proton motive force under the extreme conditions. 
      Ether lipids cannot be degraded easily and are highly stable which is also a
      requirement for life under extreme conditions. Psychrophilic and mesophilic
      Bacteria, and all Archaea adjust the lipid composition of their membranes so that
      the proton permeability of their membranes remains within a narrow range. This
      phenomenon is termed 'homeoproton permeability adaptation'. Thermophilic Bacteria
      are the only prokaryotes that are unable to control the proton permeability of
      their membranes. These organisms have to rely on the less permeable sodium ions
      in energy transducing processes in their membrane.

PMID- 10966866
TI  - MAGUK proteins: structure and role in the tight junction.
AB  - ZO-1, ZO-2 and ZO-3 are tight junction (TJ)-associated proteins that belong to
      the MAGUK family. In addition to the presence of the characteristic MAGUK modules
      (PDZ, SH3 and GK), ZOs have a distinctive carboxyl terminal with splicing
      domains, acidic- and proline-rich regions. The modular organization of these
      proteins allows them to function as scaffolds, which associate to transmembrane
      TJ proteins, the cytoskeleton and signal transduction molecules. ZOs shuttle
      between the TJ and the nucleus, where they may regulate gene expression.

PMID- 10966868
TI  - Therapeutic inhibition of the complement system. Y2K update.
AB  - Activation of complement is an essential part of the mechanism of pathogenesis of
      a large number of human diseases; its inhibition by pharmacological means is
      likely to suppress disease processes in complement mediated diseases. From this
      point of view low molecular weight synthetic inhibitors of complement are being
      developed and high molecular weight natural inhibitors of human origin present in
      plasma or embedded in cell membrane are being purified or produced in their
      recombinant forms. This review is concerned with high molecular weight
      inhibitors, some of which are already in clinical use but may be efficacious in
      many other diseases in which they have not yet been tried. C1-esterase inhibitor
      (C1-INH) concentrate prepared from human plasma is being successfully used for
      the treatment of hereditary angioneurotic edema. Recently, C1-INH has been found
      to be consumed in severe inflammation and has been shown to exert beneficial
      effects in several inflammatory conditions such as human sepsis, post-operative
      myocardial dysfunction due to reperfusion injury, severe capillary leakage
      syndrome after bone marrow transplantation, reperfusion injury after lung
      transplantation, burn, and cytotoxicity caused by IL-2 therapy in cancer. Factor
      I has been used for the treatment of factor I deficiency. Recombinant soluble
      forms of membrane cofactor protein (MCP), and decay accelerating factor (DAF)
      have not yet been tried in humans but have been shown to be effective in immune
      complex mediate inflammation in animals. Organs of pigs transgenic for one or
      more of human membrane regulators of complement namely membrane cofactor protein
      (MCP), decay accelerating factor (DAF) or CD59, are being produced for
      transplantation into humans. They have been shown to be resistant to hyperacute
      rejection in non-human primates; acute vascular rejection is still a problem in
      their clinical use. It is hoped that these observations together with future
      developments will make xeno-transplantation in clinical practice a reality.
      Several recombinant variants of complement receptor 1 (CR1) have been produced.
      The most effective of these appears to be sCR1-SLe x, sCR1 part of which inhibits
      complement and carbohydrate Sle x moiety inhibits selectin mediated interactions
      of neutrophils and lymphocytes with endothelium. Although clinical trials of sCR1
      in humans is eagerly awaited, several of the recombinant versions of sCR1 have
      been shown to suppress ischemia/reperfusion injury, thermal trauma, and immune
      complex mediated inflammation. They have also been shown to be effective in
      experimental models of systemic sclerosis, arthritis, myasthenia gravis, Guillain
      Barre syndrome and glomerulonephritis. Intravenous immunoglobulin, three of the
      most prominent properties of which are neutralization of autoantibody activity,
      suppression of autoantibody production and inhibition of complement activity, is
      being used in several diseases. These include autoimmune thrombocyopenic purpura,
      Kawasaki disease and several neurological diseases such as myasthenia gravis and
      Guillain Barre syndrome. In many uncontrolled small scale studies intravenous
      immunoglobulin has been shown to be effective in many immunological including
      dermatological diseases; controlled clinical trials in a large number of patients
      with these diseases is needed to establish the efficacy. It is hoped that in
      future therapeutic inhibition of complement will be one of the major approaches
      to combat many human diseases.

PMID- 10966869
TI  - Oxygen: friend or foe? Archaeal superoxide dismutases in the protection of intra-
      and extracellular oxidative stress.
AB  - Both "environmental chemistry" and metabolic biochemical reactions can constantly
      generate in vivo free radicals and other oxygen-derived species that can cause
      severe damage to almost all biomolecules, especially to DNA, proteins, and
      lipids. The superoxide anion has been shown to be the most readily generated and
      spread radical among organisms and it is a common intermediate of oxidative
      stress processes in the cells. The antioxidant defense system of superoxide
      dismutases (SOD) scavenges and minimizes the formation of this radical, and thus
      plays a major role in reducing cumulative oxidative damage in different cell
      compartments both in aerobic and anaerobic cells. In the cell, cytosol SODs are
      constitutively present and induced by many oxidative agents able to raise the
      superoxide concentrations. Presence of SODs, however, in extracellular cell
      associated locations demonstrates how valuable they are in maintaining the
      integrity of cells against oxidative stress generated by the cell environment,
      particularly upon increased oxygenation. Because SODs have recently been found in
      Archaea, which are prokaryotes, sometimes living in extreme environments, even in
      anaerobic ones, these enzymes can be considered essential: they may have allowed
      the evolution of aerobic respiration starting from an ancient form of oxygen
      insensitive life.

PMID- 10966870
TI  - Intact smooth muscle metabolism: its responses to cyanide poisoning and pyruvate
      stimulation.
AB  - Smooth muscle mitochondria are unique in their compartmentalization of metabolism
      with the contractile proteins and putative role in cell fate choice. In this
      study we examine the relative and quantitative differences that smooth muscle
      mitochondria have with regard to cyanide inhibition. The effect of cyanide
      poisoning in the mitochondria of smooth muscle was examined in the intact porcine
      carotid artery and intact guinea pig stomach. The respiratory responses of these
      tissues were monitored in the presence of cyanide and following the addition of
      various metabolites. In HEPES buffer with 10 mM glucose as the substrate, it was
      found that the EC50 for cyanide inhibition was 0.11+/-0.02 and 0.14+/-0.02 mM in
      the pig carotid and guinea stomach respectively. We also found that the signaling
      metabolite, pyruvate could partially reverse this inhibition. With pyruvate (10
      mM) as the substrate, the EC50 increased significantly to 6.52+/-0.11 (carotid
      artery) and 1.95+/-0. 30 (stomach) mM as well as being significantly different
      between the tissues. This apparent resistance to cyanide inhibition caused by
      pyruvate was lost when sodium bicarbonate buffer was used (EC50 in the presence
      of pyruvate of 0.13+/-0.04 and 0.25+/-0.04 for carotid and stomach respectively).
      HEPES buffer permitted pyruvate's protection from cyanide poisoning whereas
      bicarbonate buffer did not. The rate of respiration caused by pyruvate re
      stimulation was not significantly different than control in the stomach (2.63+/
      0.77 and 2.69+/-0.3??Mol O2/min/g dw respectively) but was significantly greater
      in the carotid artery. Therefore, smooth muscle with 10 mM pyruvate and 1 mM
      cyanide had a rate or respiration significantly greater than with 10 mM glucose
      alone (0.90+/-0.2 and 0.59+/-0. 06??Mol O2/min/g dw respectively). Using 31P NMR
      spectroscopy, we observed a complete normalisation of high energy phosphates and
      pH in the guinea pig stomach smooth muscle caused by pyruvate after cyanide
      poisoning. These results suggest that cyanide's toxicity of smooth muscle
      oxidative metabolism is affected by the buffer (HEPES versus Bicarbonate) and
      metabolic signalling molecules or substrates (pyruvate versus glucose) in which
      the tissues are exposed to as well as tissue to tissue variations.

PMID- 10966871
TI  - How automatically is meaning accessed: a review of the effects of attention on
      semantic processing.
AB  - This chapter attempts to review electrophysiological data that stand at the
      intersection of two large domains of research: selective attention and semantic
      processing. Analogous behavioral studies will be discussed as a way of
      introducing the reader to some of the more complex paradigms, and providing
      convergent evidence. The focus of this review will be on data that add special
      insight into the issue of semantic processing in the absence of attention.
      However, paradigms which allow semantic activation in the absence of awareness
      will also be examined as these studies have also yielded data concerning
      automatic semantic processing. It is concluded that a great deal of semantic
      processing can occur in the absence of attention as well as in the absence of
      awareness.

PMID- 10966872
TI  - Proteasomes in the archaea: from structure to function.
AB  - Survival of cells is critically dependent on their ability to rapidly adapt to
      changes in the natural environment no matter how 'extreme'the habitat. An
      interplay between protein folding and hydrolysis is emerging as a central
      mechanism for stress survival and proper cell function. In eucaryotic cells, most
      proteins destined for destruction are covalently modified by the ubiquitin-system
      and then degraded in an energy-dependent mechanism by the 26S proteasome, a
      multicatalytic protease. The 26S proteasome is composed of a 20S proteolytic core
      and 19S cap (PA700) regulator which includes six AAA+ ATPase subunits. Related
      AAA+ proteins and 20S proteasomes are found in the archaea and Gram positive
      actinomycetes. In general, 20S proteasomes form a barrel-shaped nanocompartment
      with narrow openings which isolate rather non-specific proteolytic active-sites
      to the interior of the cylinder and away from interaction with cytosolic
      proteins. The proteasome-associated AAA+ proteins are predicted to form ring-like
      structures which unfold substrate proteins for entry into the central proteolytic
      20S chamber resulting in an energy-dependent and processive destruction of the
      protein. Detailed biochemical and biophysical analysis as well as identification
      of proteasomes in archaea with developed genetic tools are providing a foundation
      for understanding the biological role of the proteasome in these unusual
      organisms.

PMID- 10966873
TI  - Stressors, stress and survival: overview.
AB  - This overview introduces the contributions in this Special Issue with the aim of
      presenting an integrated picture of it. The contributions cover several important
      areas: protein stability and function under extreme conditions, osmotic stress
      and osmoadaptation, the structural features of the cell membrane and their
      possible significance with regard to heat stress, the molecular chaperone machine
      and multicellular structures as anti-stress mechanisms, peptidyl-prolyl cis-trans
      isomerases, proteases and the proteasome, and oxidative stress and the role of
      superoxide dismutase. These topics are briefly discussed to explain the basic
      concepts underpinning them, quoting for the most part introductory articles or
      reviews that might help the non-specialist to become familiar with the central
      themes of the Special Issue. As mentioned in the Preface every effort has been
      made to discuss the archaeal features within the context of other disciplines and
      biology in general, against the background of what is known for bacteria and
      eucarya. Hopefully, this approach will help the reader in understanding what is
      unique to the archaea, what is shared between them and the members of the other
      two phylogenetic domains, and how studies in archaea impact on other fields of
      science.

PMID- 10966874
TI  - Archaeal peptidyl prolyl cis-trans isomerases (PPIases).
AB  - PPIases are ubiquitous in living organisms. While 3 families of PPIases,
      cyclophilin (CyP), FK506 binding protein (FKBP) and parvulin (Pvn), have been
      studied in detail in Eukarya and Bacteria (eubacteria), little is known about
      archaeal PPIases. Among 2 cyclophilins found in Archaea, only Halobacterium
      cyclophilin (HcCyP19) has been characterized. It is a cyclosporin A (CsA)
      sensitive CyP with a MW of 19.4kDa. The PPIase activity and CsA sensitivity of
      this CyP is higher at higher salt concentration in the medium. No parvulin or its
      homolog has been found in Archaea. Two types of FKBPs, 26-30kDa long type and 17
      18 kDa short type FKBP, have been found in Archaea. While the N-terminal regions
      of these 2 type FKBPs are similar to each other, the long type archaeal FKBP has
      an additional ca. 100 amino-acid sequence at its C-terminal region. In comparison
      with human HsFKBP12, the N-terminal region of the archaeal FKBP has 2 insertion
      sequences in the regions corresponding to Bulge and Flap of HsFKBP12. A short
      type archaeal FKBP from Methanococcus thermolithotrophicus has been shown to have
      not only a PPIase activity but also a chperone like activity, which includes
      protein refolding and aggregation suppressing activities with regard to protein
      folding intermediates. Mutational analysis revealed that this chaperone-like
      activity was independent of the PPIase activity, and that the insertion sequence
      in the region corresponding to the Flap seemed to be important.

PMID- 10966875
TI  - Molecular mechanisms regulating myogenic determination and differentiation.
AB  - The myogenic regulatory factors are necessary for the determination and terminal
      differentiation of skeletal muscle. Gene targeting experiments have demonstrated
      that MyoD and Myf5 are important for myogenic determination whereas myogenin and
      MRF4 are important for terminal differentiation and lineage maintenance. During
      development, all trunk skeletal muscle is derived from the somite. Two spatially
      distinct sources of myogenic progenitors are defined by the expression of MyoD or
      Myf5 and these give rise to hypaxial and epaxial musculature. Both in vivo and in
      vitro analyses have provided a detailed picture regarding the molecular events
      controlling lineage determination, cell migration, terminal differentiation and
      tissue repair. Signal transduction pathways regulating cell cycle, protein
      protein interactions and myogenic factor gene activation are implicated in the
      regulation of myogenesis. Recent experiments examining the origin and stem-cell
      capacity of satellite cells suggest that these cells may originate from the
      vascular system, are multipotential and may be useful for the treatment of
      several degenerative diseases.

PMID- 10966876
TI  - Plasmalemmal transport of magnesium in excitable cells.
AB  - In excitable cells, the concentration of intracellular free Mg2+ ([Mg2+]i) is
      several hundred times lower than expected if Mg2+ ions were at electrochemical
      equilibrium. Since Mg2+ is a permeant ion across the plasmalemma, it must be
      constantly extruded. An ATP-dependent Na/Mg exchanger has been proposed as the
      sole mechanism responsible for Mg2+ extrusion. However, this hypothesis fails to
      explain numerous observations including the fact that K+ and Cl- appear to be
      involved in Mg2+ transport. Until now three main limitations have hampered the
      studies of plasmalemmal Mg2+ transport: i) 28Mg, the only useful radioactive
      isotope of Mg2+, has a short half-life and is difficult to obtain; ii) squid
      giant axons, the ideal preparation to carry out transport studies under "zero
      trans" conditions, are only available during the summer months; and iii) the
      ionic fluxes mediated by the Mg2+ transporter are very small and difficult to
      measure. The purpose of this manuscript is to review how these limitations have
      been recently overcame and to propose a novel hypothesis for the plasmalemmal
      Mg2+ transporter in squid axons and barnacle muscle cells. Overcoming the
      limitations for studying the plasmalemmal Mg2+ transporter has been possible as a
      result of the following findings: i) the Mg2+ exchanger can operate in "reverse",
      thus extracellular Mg2+-dependent ionic fluxes (e.g., Na+ efflux) can be utilized
      to measure its activity; ii) internally perfused, voltage-clamped barnacle muscle
      cells which are available all year long can be used in addition to squid axons;
      and iii) phosphoinositides (e.g., PIP2) produce an 8-fold increase in the ionic
      fluxes mediated by the Mg2+ exchanger. The hypothesis that we postulate is that,
      in squid giant axons and barnacle muscle cells, a 2Na+2K+2Cl:1Mg exchanger is
      responsible for transporting Mg2+ across the plasmalemma and for maintaining
      [Mg2+]i under steady-state conditions.

PMID- 10966877
TI  - Osmoadaptation and osmoregulation in archaea.
AB  - The response of archaea to changes in external NaCl is reviewed and compared to
      what is known about osmoadaptation and osmoregulation in bacteria and eukaryotes.
      Cells placed in altered external NaCl exhibit short term and long term responses.
      The earliest events are likely to be water movement through aquaporin-like
      channels (efflux if external NaCl has been increased, influx into the cell if the
      external NaCl has been decreased) and ion movement (e.g., K+ moving in the
      direction opposite to water flow) through channels sensitive to osmotic pressure.
      Accumulation of organic solutes, either by uptake from the medium or de novo
      synthesis, is triggered after these initial changes. Archaea have some unique
      organic solutes (osmolytes) that are not used by other organisms. These as well
      as other more common solutes have a role in stabilizing macromolecules from
      denaturation. Many osmolytes are distinguished by their stability in the cell and
      their lack of strong interactions with cellular components. A cell may respond by
      accumulating one or more temporary osmolytes, then over time readjust the
      intracellular solute distribution to what is optimal for cell growth under the
      new conditions. Coupled with the movement and accumulation of solutes is the
      induction of stress proteins (e.g., chaperonins) and, in some cases,
      transcriptional regulation of key enzymes. The response to NaCl stress of
      Methanococcus thermolithotrophicus is presented as an example of how one
      particular archaeon responds and adapts to altered osmotic pressure. Clearly, the
      detailed response of other archaea to osmotic stress will be needed in order to
      identify features (aside from some of the organic osmolytes) unique to the
      organisms in this kingdom.

PMID- 10966878
TI  - Apoptosis - when the cells begin to dance.
AB  - We present a 24-hour time-lapse videosequence of in vitro behavior of Hep-2 cells
      treated with 10 m g/ml Etoposide, a topoisomerase II inhibitor. The cell behavior
      was recorded by a Mitsubishi video recorder, HS-S5600. In the presented sequence,
      we show the typical cell rounding accompanied by formation of numerous
      pseudopodia and rapid rhythmical contractions, so called membrane blebbing known
      as "dance of death".

PMID- 10966879
TI  - Protein stability in extremophilic archaea.
AB  - Extremophilic microorganisms have adapted their molecular machinery to grow and
      thrive under the most adverse environmental conditions. These microorganisms have
      found their natural habitat at the boiling and freezing point of water, in high
      salt concentration and at extreme pH values. The extremophilic proteins, selected
      by Nature to withstand this evolutionary pressure, represent a wide research
      field for scientists from different disciplines and the study of the determinants
      of their stability has been an important task for basic and applied research. A
      surprising conclusion emerges from these studies: there are no general rules to
      achieve protein stabilization. Each extremophilic protein adopts various
      strategies and the outstanding adaptation to extreme temperature and solvent
      conditions is realized through the same weak electrostatic and hydrophobic
      interactions among the ordinary amino acid residues which are also responsible
      for the proper balance between protein stability and flexibility in mesophilic
      proteins.

PMID- 10966880
TI  - Investigating development of infective stage larvae of filarial nematodes.
AB  - Lymphatic filariasis is a parasitic disease affecting millions of individuals and
      one of the leading causes of disability in the world. However, considering the
      magnitude of filariasis as a public health problem, relatively little is known
      about the basic biology of the disease and its causative agents, filarial
      nematodes. In this paper, the biology of the infective stage larvae of the
      nematodes responsible for lymphatic filariasis and the approaches used to study
      their development are reviewed.

PMID- 10966881
TI  - Searching for the determinants of intestinal calcium absorption.

PMID- 10966882
TI  - Iron treatment and human intestinal Caco-2 cells.

PMID- 10966883
TI  - Provocative relation between soy and bone maintenance.

PMID- 10966884
TI  - Dairy foods and bone health: examination of the evidence.
AB  - It is unclear whether dairy foods promote bone health in all populations and
      whether all dairy foods are equally beneficial. The objective of this review was
      to determine whether scientific evidence supports the recommendation that dairy
      foods be consumed daily for improved bone health in the general US population.
      Studies were reviewed that examined the relation of dairy foods to bone health in
      all age, sex, and race groups. Outcomes were classified according to the strength
      of the evidence by using a priori guidelines and were categorized as favorable,
      unfavorable, or not statistically significant. Of 57 outcomes of the effects of
      dairy foods on bone health, 53% were not significant, 42% were favorable, and 5%
      were unfavorable. Of 21 stronger-evidence studies, 57% were not significant, 29%
      were favorable, and 14% were unfavorable. The overall ratio of favorable to
      unfavorable effects in the stronger studies was 2.0 (4.0 in <30-y-olds, 1.0 in 30
      50-y-olds, and 1.0 in >50-y-olds). Males and ethnic minorities were severely
      underrepresented. Dairy foods varied widely in their content of nutrients known
      to affect calcium excretion and skeletal mass. Foods such as milk and yogurt are
      likely to be beneficial; others, such as cottage cheese, may adversely affect
      bone health. Of the few stronger-evidence studies of dairy foods and bone health,
      most had outcomes that were not significant. However, white women <30 y old are
      most likely to benefit. There are too few studies in males and minority ethnic
      groups to determine whether dairy foods promote bone health in most of the US
      population.

PMID- 10966885
TI  - Decreased bioavailability of vitamin D in obesity.
AB  - BACKGROUND: Obesity is associated with vitamin D insufficiency and secondary
      hyperparathyroidism. OBJECTIVE: This study assessed whether obesity alters the
      cutaneous production of vitamin D(3) (cholecalciferol) or the intestinal
      absorption of vitamin D(2) (ergocalciferol). DESIGN: Healthy, white, obese [body
      mass index (BMI; in kg/m(2)) > or = 30] and matched lean control subjects (BMI
      </= 25) received either whole-body ultraviolet radiation or a pharmacologic dose
      of vitamin D(2) orally. RESULTS: Obese subjects had significantly lower basal 25
      hydroxyvitamin D concentrations and higher parathyroid hormone concentrations
      than did age-matched control subjects. Evaluation of blood vitamin D(3)
      concentrations 24 h after whole-body irradiation showed that the incremental
      increase in vitamin D(3) was 57% lower in obese than in nonobese subjects. The
      content of the vitamin D(3) precursor 7-dehydrocholesterol in the skin of obese
      and nonobese subjects did not differ significantly between groups nor did its
      conversion to previtamin D(3) after irradiation in vitro. The obese and nonobese
      subjects received an oral dose of 50000 IU (1.25 mg) vitamin D(2). BMI was
      inversely correlated with serum vitamin D(3) concentrations after irradiation (r
      = -0.55, P: = 0.003) and with peak serum vitamin D(2) concentrations after
      vitamin D(2) intake (r = -0.56, P: = 0.007). CONCLUSIONS: Obesity-associated
      vitamin D insufficiency is likely due to the decreased bioavailability of vitamin
      D(3) from cutaneous and dietary sources because of its deposition in body fat
      compartments.

PMID- 10966886
TI  - Healthy percentage body fat ranges: an approach for developing guidelines based
      on body mass index.
AB  - BACKGROUND: Although international interest in classifying subject health status
      according to adiposity is increasing, no accepted published ranges of percentage
      body fat currently exist. Empirically identified limits, population percentiles,
      and z scores have all been suggested as means of setting percentage body fat
      guidelines, although each has major limitations. OBJECTIVE: The aim of this study
      was to examine a potential new approach for developing percentage body fat
      ranges. The approach taken was to link healthy body mass index (BMI; in kg/m(2))
      guidelines established by the National Institutes of Health and the World Health
      Organization with predicted percentage body fat. DESIGN: Body fat was measured in
      subjects from 3 ethnic groups (white, African American, and Asian) who were
      screened and evaluated at 3 universities [Cambridge (United Kingdom), Columbia
      (United States), and Jikei (Japan)] with use of reference body-composition
      methods [4-compartment model (4C) at 2 laboratories and dual-energy X-ray
      absorptiometry (DXA) at all 3 laboratories]. Percentage body fat prediction
      equations were developed based on BMI and other independent variables. RESULTS: A
      convenient sample of 1626 adults with BMIs < or =35 was evaluated. Independent
      percentage body fat predictor variables in multiple regression models included
      1/BMI, sex, age, and ethnic group (R: values from 0.74 to 0.92 and SEEs from 2.8
      to 5.4% fat). The prediction formulas were then used to prepare provisional
      healthy percentage body fat ranges based on published BMI limits for underweight
      (<18.5), overweight (> or =25), and obesity (> or =30). CONCLUSION: This proposed
      approach and initial findings provide the groundwork and stimulus for
      establishing international healthy body fat ranges.

PMID- 10966887
TI  - Why are nutritionally stunted children at increased risk of obesity? Studies of
      metabolic rate and fat oxidation in shantytown children from Sao Paulo, Brazil.
AB  - BACKGROUND: Previous research suggested that nutritionally stunted children may
      have increased risk of obesity, but little is known about potential underlying
      mechanisms. OBJECTIVE: We sought to test the hypothesis that stunted children
      have a low metabolic rate and impaired fat oxidation relative to nonstunted
      children. DESIGN: The subjects were 58 prepubertal boys and girls aged 8-11 y
      from the shantytowns of Sao Paulo, Brazil. Twenty-eight were stunted (height-for
      age z score <-1.5) and 30 had similar weight-for-height but normal height (height
      for-age z score >-1.5). Parents of children in the 2 groups had equivalent height
      and body mass index values. Fasting and postprandial energy expenditure,
      respiratory quotient (RQ), and substrate oxidation were measured with indirect
      calorimetry in a 3-d resident study in which all food was provided and body
      composition was measured with dual-energy X-ray absorptiometry. RESULTS: Stunted
      children had normal resting energy expenditure relative to body composition
      compared with control children (4559 +/- 90 and 4755 +/- 86 kJ/d, respectively;
      P: = 0.14) and had normal postprandial thermogenesis (2.4 +/- 0.3% and 2.0 +/-
      0.3% of meal load, respectively; P: = 0.42). However, fasting RQ was
      significantly higher in the stunted group (0.92 +/- 0.009 compared with 0.89 +/-
      0.007; P: = 0.04) and consequently, fasting fat oxidation was significantly lower
      (25 +/- 2% compared with 34 +/- 2% of energy expenditure; P: < 0.01).
      CONCLUSIONS: Childhood nutritional stunting is associated with impaired fat
      oxidation, a factor that predicted obesity in other at-risk populations. This
      finding may help explain recent increases in body fatness and the prevalence of
      obesity among stunted adults and adolescents in developing countries.

PMID- 10966888
TI  - Dietary restriction and walking reduce fat deposition in the midthigh in obese
      older women.
AB  - BACKGROUND: It is suggested that fat deposition within midthigh muscle,
      represented by low-density lean tissue, increases with deconditioning and obesity
      and is associated with risk factors for cardiovascular disease (CVD) in women.
      OBJECTIVE: We determined the effects of a 6-mo weight loss and walking (3
      times/wk) program (WL+AEX) on midthigh low-density lean tissue and glucose and
      lipid metabolism in 24 sedentary, obese [body mass index (kg/m(2)): 32 +/- 1
      (mean +/- SEM)] postmenopausal women aged 58 +/- 1 y. DESIGN: Total body fat and
      fat-free mass were measured by using dual-energy X-ray absorptiometry.
      Intraabdominal fat (IAF), subcutaneous abdominal fat (SAF), midthigh fat,
      midthigh muscle, and midthigh low-density lean tissue areas were measured by
      using computed tomography. Glucose and insulin responses were determined with a 3
      h oral-glucose-tolerance test. RESULTS: Body weight decreased 8% (P: < 0.001) and
      maximal aerobic capacity increased 8% (P: < 0.001) with the weight loss and
      walking program. Total body fat decreased by 15% (P: < 0.001) whereas fat-free
      mass did not change. IAF and SAF decreased by 18% and 16%, respectively (P: < 0.
      001). Midthigh fat and midthigh low-density lean tissue decreased by 16% and 18%,
      respectively (P: < 0.001), and midthigh muscle area increased by 7% (P: < 0.05).
      Fasting plasma insulin decreased by 12% and total glucose and insulin areas under
      the curve decreased by 6% and 24%, respectively (P: < 0.05). HDL-cholesterol
      concentrations increased 8% (P: < 0.05) and triacylglycerol concentrations
      decreased 19% (P: < 0.001). CONCLUSION: Increased physical fitness and weight
      loss reduce midthigh low-density lean tissue and improve glucose and lipid
      metabolic risk factors for CVD in obese postmenopausal women.

PMID- 10966889
TI  - Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic
      acid and docosahexaenoic acid is not associated with greater in vivo lipid
      peroxidation compared with oils rich in oleate and linoleate as assessed by
      plasma malondialdehyde and F(2)-isoprostanes.
AB  - BACKGROUND: Although the replacement of dietary saturated fat with unsaturated
      fat has been advocated to reduce the risk of cardiovascular disease, diets high
      in polyunsaturated fatty acids (PUFAs) could increase lipid peroxidation,
      potentially contributing to the pathology of atherosclerosis. OBJECTIVE: The
      objective of this study was to examine indexes of in vivo lipid peroxidation,
      including free F(2)-isoprostanes, malondialdehyde (MDA), and thiobarbituric acid
      reacting substances (TBARS), in the plasma of postmenopausal women taking dietary
      oil supplements rich in oleate, linoleate, and both eicosapentaenoic acid and
      docosahexaenoic acid. DESIGN: Fifteen postmenopausal women took 15 g sunflower
      oil/d, providing 12.3 g oleate/d; safflower oil, providing 10.5 g linoleate/d;
      and fish oil, providing 2.0 g EPA/d and 1.4 g DHA/d in a 3-treatment crossover
      trial. RESULTS: Plasma free F(2)-isoprostane concentrations were lower after fish
      oil supplementation than after sunflower-oil supplementation (P: = 0.003). When
      plasma free F(2)-isoprostane concentrations were normalized to plasma arachidonic
      acid concentrations, significant differences among the supplements were
      eliminated. Plasma MDA concentrations were lower after fish-oil supplementation
      than after sunflower-oil supplementation (P: = 0.04), whereas plasma TBARS were
      higher after fish-oil supplementation than after sunflower oil (P: = 0.003) and
      safflower oil (P: = 0.001) supplementation. When plasma MDA concentrations were
      normalized to plasma PUFA concentrations, significant differences were
      eliminated, but TBARS remained higher after fish-oil supplementation than after
      sunflower oil (P: = 0.01) and safflower-oil (P: = 0.0003) supplementation.
      CONCLUSIONS: With fish-oil supplementation, there was no evidence of increased
      lipid peroxidation when assessed by plasma F(2)-isoprostanes and MDA, although
      plasma TBARS was higher than with sunflower-oil and safflower-oil
      supplementation.

PMID- 10966890
TI  - Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous
      system in healthy subjects.
AB  - BACKGROUND: Fatty acids have been shown to stimulate the sympathetic nervous
      system in rats. Power spectral analysis of heart rate variability (HRV) is a safe
      and useful tool with which to evaluate cardiac autonomic nervous system (ANS)
      activity. Whether changes in plasma fatty acid concentrations affect the
      sympathetic nervous system or HRV in humans is unknown. OBJECTIVE: We
      investigated the possible changes in HRV after a significant increase in plasma
      fatty acid concentration. DESIGN: Subjects were randomly assigned to receive an
      infusion of lipid emulsion (10% triacylglycerol emulsion for 180 min) + heparin
      (a bolus of 200 U followed by 0.2 U*min(-)(1)*kg body wt(-)(1); n = 20) or 0.9%
      NaCl (for 180 min; n = 10). RESULTS: Lipid emulsion + heparin infusion was
      associated with a rise in plasma epinephrine and norepinephrine concentrations.
      The rise in plasma fatty acid concentration was associated with a significant
      decline in the RR interval (P: < 0.03) and in total power (P: < 0.03). Analysis
      of the different components of HRV showed that lipid emulsion + heparin infusion
      stimulated low- frequency (LF) components (P: < 0.03 at the second hour and P: <
      0. 01 at the third hour) and inhibited high-frequency (HF) components (P: < 0.03
      at the second and third hours). Consequently, the LF-HF ratio was significantly
      stimulated (P: < 0.03 at the second hour and P: < 0.01 at the third hour). Such
      results persisted, although attenuated, when the study was repeated in
      association with a propranolol infusion (n = 8). CONCLUSION: Elevated plasma
      fatty acid concentrations may stimulate cardiac autonomic nervous system
      activity.

PMID- 10966891
TI  - Oxidation of plasma proteins is not increased after supplementation with
      eicosapentaenoic and docosahexaenoic acids.
AB  - BACKGROUND: It is generally thought that as the intake of dietary polyunsaturated
      fatty acids increases, so should that of alpha-tocopherol, to protect the
      polyunsaturated fatty acids from increased in vivo peroxidation. However, there
      are little quantitative data about the concentration of alpha-tocopherol that is
      necessary when eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are
      consumed. OBJECTIVE: The purpose of this study was to measure changes produced in
      2 indexes of lipid oxidation after supplementation with EPA and DHA from fish oil
      and 3 doses of RRR-alpha-tocopheryl acetate in postmenopausal women. DESIGN:
      Daily supplements of fish oil providing 2.5 g EPA and 1.8 g DHA and 0, 100, 200,
      or 400 mg alpha-tocopheryl acetate were given to 46 postmenopausal women in a 4
      treatment, 4-period crossover design. RESULTS: The supplements increased plasma
      concentrations of EPA, DHA, and alpha-tocopherol. The fish-oil supplement
      increased the plasma concentration of thiobarbituric acid-reactive substances
      (TBARS) (P: = 0.0001) but not that of oxidatively modified protein, as indicated
      by the carbonyl content. The alpha-tocopheryl acetate and fish-oil supplements
      had no significant effect on plasma concentrations of TBARS or oxidized protein.
      CONCLUSIONS: Although these data show a small but statistically significant
      increase in oxidative stress on the basis of plasma TBARS concentrations after
      the consumption of EPA and DHA, the clinical relevance of this change is
      questionable. In addition, as supplements of alpha-tocopheryl acetate were added
      to the diet, neither the plasma TBARS concentration nor the protein oxidation
      changed. Consequently, the results of this study indicate that there is no basis
      for vitamin E supplementation after consumption of EPA and DHA.

PMID- 10966892
TI  - Efficacy of a vitamin A-fortified wheat-flour bun on the vitamin A status of
      Filipino schoolchildren.
AB  - BACKGROUND: Wheat flour is a possible food vehicle for vitamin A fortification.
      OBJECTIVE: This study assessed the efficacy of consumption of a vitamin A
      fortified wheat-flour bun (pandesal) on the vitamin A status of school-age
      children. DESIGN: This was a double-masked clinical trial conducted in 396 and
      439 children aged 6-13 y attending 4 rural schools in the Philippines. The
      children were randomly assigned to a vitamin A-fortified (experimental) or
      nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing
      approximately 133 microg retinol equivalents) or a nonfortified pandesal was
      consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin
      concentration, anthropometric status, morbidity, and dietary intake were assessed
      at baseline and 30 wk later. A modified relative dose response (MRDR) was
      assessed in a subsample of 20% of the children ( approximately 75/group) with the
      lowest initial serum retinol concentration at the 30-wk follow-up. RESULTS:
      Baseline serum retinol significantly modified the effect of the intervention. The
      fortified group, whose initial serum retinol concentrations were below the
      median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at
      the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A
      status was also evident in the MRDR subsample. End-of-study differences in the
      MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of
      children with inadequate liver vitamin A stores by 50% (15.3% compared with
      28.6%; P: = 0.05). CONCLUSIONS: Daily consumption of vitamin A-fortified pandesal
      significantly improved the vitamin A status of Filipino school-age children with
      marginal-to-low initial serum retinol concentrations.

PMID- 10966893
TI  - Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly
      men and women.
AB  - BACKGROUND: Supplementation with calcium and vitamin D reduces bone loss and
      prevents fractures in elderly people, but it is not known whether any lasting
      benefit remains if the supplements are discontinued. OBJECTIVE: The objective was
      to determine whether gains in bone mineral density (BMD) induced by calcium and
      vitamin D supplementation persist after supplement withdrawal. DESIGN: Two
      hundred ninety-five healthy, elderly men and women (aged >/=68 y) who had
      completed a 3-y randomized, placebo-controlled trial of calcium and vitamin D
      supplementation were followed for an additional 2 y during which no study
      supplements were given. BMD was measured by dual-energy X-ray absorptiometry, and
      biochemical variables related to calcium metabolism and bone turnover were
      measured. RESULTS: In the 128 men, supplement-induced increases in spinal and
      femoral neck BMD were lost within 2 y of supplement discontinuation, but small
      benefits in total-body BMD remained. In the 167 women, there were no lasting
      benefits in total-body BMD or at any bone site. Consistent with the observations
      on BMD, the bone turnover rates in both men and women (as measured by serum
      osteocalcin concentrations) returned to their original higher concentrations
      within the same 2-y period. CONCLUSION: Discontinued calcium and vitamin D
      supplementation has limited cumulative effect on bone mass in men and women aged
      >/=68 y.

PMID- 10966894
TI  - Assessment of vitamin B-12, folate, and vitamin B-6 status and relation to sulfur
      amino acid metabolism in neonates.
AB  - BACKGROUND: Total serum homocysteine (tHcy) has been used as an indicator of
      intracellular vitamin B-12, vitamin B-6, and folate status in adults, but data
      for neonates and infants are lacking. Vitamin B-12 deficiency may have fatal
      effects on neurologic development in infants; therefore, early diagnosis is
      crucial. OBJECTIVE: Our aim was to provide a reference range for tHcy in neonates
      and to explore the relation of tHcy to 1) serum vitamin concentrations, 2) the
      product of the transsulfuration pathway (cysteine), and 3) nutritional factors.
      DESIGN: tHcy, cysteine, folate, vitamin B-12, and vitamin B-6 were measured in
      123 healthy, breast-fed neonates. The influence of nutrition (formula or human
      milk) on these variables was investigated in 60 infants. RESULTS: The mean (+/
      SD) tHcy concentration was 7.8 +/- 3.1 micromol/L. tHcy showed a linear
      association with log vitamin B-12 (r = -0.64, P: < 0. 001), red blood cell folate
      (r = -0.33, P: < 0.001), and cysteine (r = 0.36, P: < 0.001). The strongest
      linear association was found between tHcy and the ratio of log cysteine to log
      vitamin B-12 (r = 0.71, P: < 0.0001). We found more neonates with probable tissue
      deficiencies of vitamin B-12 and folate on the basis of tHcy measurements than
      was expected from the analysis of serum vitamin concentrations alone (15.4%
      compared with 9.7%). Breast-fed infants had significantly lower vitamin B-12
      concentrations and significantly higher serum tHcy and cysteine concentrations
      and ratios of log cysteine to log vitamin B-12 than did formula-fed infants (P: <
      0.001). CONCLUSIONS: tHcy can be used as a functional indicator of vitamin B-12
      and folate status in neonates. The ratio of cysteine to vitamin B-12 can be used
      as an additional index of impaired intracellular Hcy metabolism. tHcy and
      cysteine concentrations in infants are affected by nutritional factors.

PMID- 10966895
TI  - Dietary protein and phosphorus do not affect calcium absorption.
AB  - BACKGROUND: Variation in absorption efficiency explains more of the variability
      in calcium balance than does actual calcium intake. Several investigators have
      suggested that the relatively high phosphorus and protein intakes of the diets of
      industrialized nations reduce calcium absorption and thereby aggravate the
      problem of calcium deficiency. OBJECTIVE: My objective was to test whether
      variation in phosphorus and protein intakes is associated with variation in
      calcium absorption. DESIGN: One hundred ninety-one Roman Catholic nuns aged 48.7
      +/- 7.0 y were studied approximately 3 times each over a >20-y period with a full
      metabolic balance regimen; controlled, chemically analyzed diets; and double
      tracer measurement of calcium absorption. RESULTS: Although the expected
      associations with absorption were found for age, calcium intake, and estrogen
      status, no association was observed for intakes of either phosphorus or protein.
      CONCLUSION: Phosphorus and protein intakes do not contribute to the wide
      variability in calcium absorption efficiency.

PMID- 10966896
TI  - Signs of impaired cognitive function in adolescents with marginal cobalamin
      status.
AB  - BACKGROUND: Lack of cobalamin may lead to neurologic disorders, which have been
      reported in strict vegetarians. OBJECTIVE: The objective of this study was to
      investigate whether cognitive functioning is affected in adolescents (aged 10-16
      y) with marginal cobalamin status as a result of being fed a macrobiotic diet up
      to an average age of 6 y. DESIGN: Data on dietary intake, psychological test
      performance, and biochemical variables of cobalamin status were collected from 48
      adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y,
      subsequently followed by lactovegetarian or omnivorous diets, and from 24
      subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty
      one subjects from the previously macrobiotic group were cobalamin deficient
      according to their plasma methylmalonic acid concentrations. Seventeen previously
      macrobiotic subjects and all control subjects had normal cobalamin status.
      RESULTS: The control subjects performed better on most psychological tests than
      did macrobiotic subjects with low or normal cobalamin status. A significant
      relation between test score and cobalamin deficiency (P: = 0.01) was observed for
      a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: 
      0.48, -0.08). This effect became more pronounced (P: = 0.003) within the subgroup
      of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14).
      CONCLUSION: Our data suggest that cobalamin deficiency, in the absence of
      hematologic signs, may lead to impaired cognitive performance in adolescents.

PMID- 10966897
TI  - Functional and molecular responses of human intestinal Caco-2 cells to iron
      treatment.
AB  - BACKGROUND: Divalent metal transporter 1 (DMT1), HFE, and stimulator of iron
      transport (SFT) are transmembrane proteins that have been implicated in the
      regulation of iron homeostasis. OBJECTIVE: The objective of this study was to
      investigate whether absorption and transepithelial movement of iron correlated
      with gene expression of DMT1, HFE, and SFT in an experimental model of human
      absorptive enterocytes. DESIGN: Caco-2 cells were exposed to iron-supplemented
      media in either the presence or the absence of serum for 24, 72, and 168 h. At
      each time point, the uptake and transepithelial movement of iron were examined
      and gene expression of DMT1, HFE, and SFT was measured. Manganese and zinc
      absorption was also examined at 168 h. RESULTS: Iron treatment in the presence or
      absence of serum reduced the uptake and transepithelial movement of iron by
      approximately 50% after 72 and 168 h. No effect was observed at 24 h. The uptake
      and transepithelial movement of manganese were similar to those of iron at 168 h,
      whereas the effects on zinc were less pronounced. In the absence of serum, iron
      treatment was associated with a reduction of DMT1 expression by 50% at 72 and 168
      h. HFE expression was dependent on serum, but iron treatment did not alter HFE
      expression. SFT expression was not affected by iron. CONCLUSIONS: Iron treatment
      decreased cellular uptake of iron, manganese, and zinc, suggesting that these
      metals may utilize the same apical transporter. The transepithelial movement of
      iron and manganese, but not of zinc, was reduced across iron-treated Caco-2
      cells, suggesting that iron and manganese are regulated by the same mechanism at
      the basolateral membrane. The gene expression of DMT1, HFE, and SFT did not fully
      correlate with the functional responses of Caco-2 cells. This may have been a
      result of posttranscriptional regulation of these genes or regulation of other
      genes involved in the uptake and transepithelial movement of iron in Caco-2
      cells.

PMID- 10966898
TI  - Relation between insulin resistance and plasma concentrations of lipid
      hydroperoxides, carotenoids, and tocopherols.
AB  - BACKGROUND: It is not known whether total circulating lipid hydroperoxides are
      increased in insulin-resistant individuals and whether this correlates with
      depletion of liposoluble antioxidant vitamins that are consumed during lipid
      peroxidation. OBJECTIVE: The goal of this study was to define the relation
      between resistance to insulin-mediated glucose disposal and plasma concentrations
      of lipid hydroperoxides and liposoluble antioxidant vitamins in healthy
      volunteers. DESIGN: Insulin-mediated glucose disposal was determined in 36
      healthy, nondiabetic volunteers by measuring their steady-state plasma insulin
      (SSPI) and glucose (SSPG) concentrations in response to a 180-min constant
      infusion of octreotide, insulin, and glucose. In addition, fasting plasma
      concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins were
      determined by using the FOX 2 assay and liquid chromatography. RESULTS:
      Statistically significant direct relations were observed between SSPG and mean
      arterial blood pressure (r = 0.44, P: = 0.008) and plasma lipid hydroperoxide
      concentrations (r = 0.42, P: = 0.01), whereas significant inverse correlations
      were found between SSPG and alpha-carotene (r = -0.58, P: = 0.0002), beta
      carotene (r = -0.49, P: = 0.004), lutein (r = -0.35, P: = 0.04), alpha-tocopherol
      (r = -0. 36, P: = 0.04), and delta-tocopherol (r = -0.45, P: = 0.007).
      CONCLUSIONS: Variations in insulin-mediated glucose disposal in healthy
      individuals are significantly related to plasma concentrations of lipid
      hydroperoxides and liposoluble antioxidant vitamins. These findings suggest that
      total plasma lipid peroxidation is increased in insulin-resistant individuals at
      an early, preclinical stage, ie, well before the development of glucose
      intolerance and type 2 diabetes.

PMID- 10966899
TI  - Multifrequency bioelectrical impedance analysis in women with a normal and
      hypertensive pregnancy.
AB  - BACKGROUND: An increase in total body water is common in normal pregnancy. It is
      thought to be an important mechanism of maternal adaptation to pregnancy.
      OBJECTIVE: The aim of the present study was to assess longitudinal changes in
      body water compartments in pregnant women and to correlate these measurements
      with the course of pregnancy. DESIGN: One hundred seventy-three pregnant women
      with apparently normal, single pregnancies participated in this longitudinal
      study. Anthropometric measurements and multifrequency bioelectrical impedance
      were performed during the first, second, and third trimesters of pregnancy.
      RESULTS: One hundred three of the women completed all of the measurements; 50 of
      the women had a normal pregnancy and 13 had gestational hypertension. Total body
      water, extracellular water, and intracellular water values in normal pregnancies
      showed a significant, progressive increase throughout pregnancy. In women with
      gestational hypertension, total body water, extracellular water, and
      intracellular water values showed an opposite trend, suggesting a lack of plasma
      volume expansion through fluid-retention mechanisms. CONCLUSIONS: Our results
      show that multifrequency bioelectrical impedance analysis can be used to monitor
      variations in body water compartments in normal pregnancy and detect gestational
      hypertension.

PMID- 10966900
TI  - An unfermented gel component of psyllium seed husk promotes laxation as a
      lubricant in humans.
AB  - BACKGROUND: In addition to increasing stool weight, supplements of psyllium seed
      husk produce stools that are slick and gelatinous. OBJECTIVE: Our purpose was to
      test the hypothesis that a gel-forming fraction of psyllium escapes microbial
      fermentation and is responsible for the characteristics that enhance laxation.
      DESIGN: Fifteen healthy adults consumed controlled diets for two 7-d periods, one
      of which included 8.8 g dietary fiber provided by 15 g/d of a psyllium seed husk
      preparation. All stools were collected and evaluated and diet was monitored
      throughout. RESULTS: Psyllium significantly increased the apparent viscosity of
      an aqueous stool extract, stool moisture, and wet and dry stool weights. A very
      viscous fraction, not present in low-fiber stool and containing predominantly 2
      sugars that are also found in abundance in psyllium husk, was isolated from
      psyllium stool. CONCLUSIONS: In contrast with other viscous fibers that are
      fermented completely in the colon, a component of psyllium is not fermented. This
      gel provided lubrication that facilitated propulsion of colon contents and
      produced a stool that was bulkier and more moist than were stools resulting with
      use of comparable amounts of other bowel-regulating fiber sources.

PMID- 10966901
TI  - Response of glutamine metabolism to glutamine-supplemented parenteral nutrition.
AB  - BACKGROUND: Increasing evidence suggests that glutamine is important for the
      function of many organ systems and supports the use of glutamine-enriched total
      parenteral nutrition (TPN) during severe illness. However, the effect of
      prolonged glutamine supplementation on glutamine kinetics has not been studied.
      OBJECTIVE: We investigated the effect of 8-10 d of TPN enriched with glutamine
      dipeptides on glutamine kinetics. DESIGN: Twenty-three preoperative patients were
      randomly allocated to receive either TPN enriched with glutamine dipeptides (60
      micromol glutamine*kg body wt(-1)*h(-1)) or isonitrogenous, isoenergetic,
      glutamine-free TPN. A primed, continuous, 6-h intravenous infusion of L-[5
      (15)N]glutamine and L-[1-(13)C]leucine was given before (baseline) and 8-10 d
      after the TPN solutions were administered. Baseline measurements were performed
      after a 40-h administration of a standard solution of glucose and amino acids (no
      glutamine). RESULTS: Glutamine-enriched TPN increased the total appearance rate
      of glutamine (P: < 0.05) but did not inhibit or increase the endogenous
      appearance rate. The standard TPN solution also increased the glutamine
      appearance rate (P: < 0.05), but the change was much smaller than in the
      glutamine-supplemented group (P: < 0.01). The plasma glutamine concentration did
      not rise significantly during either treatment, suggesting increased tissue
      glutamine utilization, especially in the glutamine-supplemented group.
      CONCLUSION: In view of the enhanced glutamine requirements in response to trauma
      and disease by tissues such as those of the gut, the immune system, and the
      liver, increased glutamine availability during glutamine-enriched TPN may be
      beneficial preoperatively in patients with gastrointestinal disease.

PMID- 10966902
TI  - Total-body skeletal muscle mass: development and cross-validation of
      anthropometric prediction models.
AB  - BACKGROUND: Skeletal muscle (SM) is a large body compartment of biological
      importance, but it remains difficult to quantify SM with affordable and practical
      methods that can be applied in clinical and field settings. OBJECTIVE: The
      objective of this study was to develop and cross-validate anthropometric SM mass
      prediction models in healthy adults. DESIGN: SM mass, measured by using whole
      body multislice magnetic resonance imaging, was set as the dependent variable in
      prediction models. Independent variables were organized into 2 separate formulas.
      One formula included mainly limb circumferences and skinfold thicknesses [model
      1: height (in m) and skinfold-corrected upperarm, thigh, and calf girths (CAG,
      CTG, and CCG, respectively; in cm)]. The other formula included mainly body
      weight (in kg) and height (model 2). The models were developed and cross
      validated in nonobese adults [body mass index (in kg/m(2)) < 30]. RESULTS: Two SM
      (in kg) models for nonobese subjects (n = 244) were developed as follows: SM = Ht
      x (0.00744 x CAG(2) + 0.00088 x CTG(2) + 0.00441 x CCG(2)) + 2.4 x sex - 0.048 x
      age + race + 7.8, where R:(2) = 0.91, P: < 0.0001, and SEE = 2.2 kg; sex = 0 for
      female and 1 for male, race = -2.0 for Asian, 1.1 for African American, and 0 for
      white and Hispanic, and SM = 0.244 x BW + 7.80 x Ht + 6.6 x sex - 0.098 x age +
      race - 3.3, where R:(2) = 0.86, P: < 0.0001, and SEE = 2.8 kg; sex = 0 for female
      and 1 for male, race = -1.2 for Asian, 1.4 for African American, and 0 for white
      and Hispanic. CONCLUSION: These 2 anthropometric prediction models, the first
      developed in vivo by using state-of-the-art body-composition methods, are likely
      to prove useful in clinical evaluations and field studies of SM mass in nonobese
      adults.

PMID- 10966903
TI  - Effects of sesamin-supplemented dietary fat emulsions on the ex vivo production
      of lipopolysaccharide-induced prostanoids and tumor necrosis factor alpha in
      rats.
AB  - BACKGROUND: Sesamin, a nonfat constituent of sesame oil, inhibits Delta(5)
      desaturase activity, resulting in accumulation of dihomo-gamma-linolenic acid
      (DGLA), which displaces arachidonic acid (AA) and consequently decreases the
      formation of proinflammatory 2-series prostaglandins. OBJECTIVE: We sought to
      determine whether dietary supplementation with sesamin augments the
      antiinflammatory effects of dietary linseed oil in rats. DESIGN: We investigated
      the effects of continuous tube feedings of emulsions containing safflower oil or
      linseed oil with sesamin (SO+ and LO+) or without sesamin (SO and LO) on liver
      fatty acid composition and on endotoxin-induced production of prostaglandin E(2),
      6-keto-prostaglandin F(1alpha), and tumor necrosis factor alpha (TNF-alpha) by
      whole blood from rats (n = 6 per diet group). RESULTS: We found a significant
      accumulation of DGLA only in the liver phospholipids of animals fed SO+ and LO+
      (1.8 +/- 0.2 and 1.4 +/- 0.3 mol%, respectively), which suggests that sesamin
      inhibited Delta(5)-desaturation of n-6 fatty acids. These changes were associated
      with significant reductions in plasma prostaglandin E(2) concentrations in
      animals fed SO+ compared with those fed SO (P: < 0. 05). Despite a significant
      reduction in tissue AA content in the LO group, the prostaglandin E(2)
      concentrations did not differ significantly from those of the SO group. Plasma
      concentrations of TNF-alpha were significantly lower (P: < 0.05) in the animals
      fed LO+ than in those fed SO (199 +/- 48 and 488 +/- 121 ng/L, respectively).
      CONCLUSION: These data indicate that in rats, tube feedings of diets containing
      sesamin exerted antiinflammatory effects that were augmented by concurrent
      consumption of linseed oil.

PMID- 10966904
TI  - Status of selected nutrients and progression of human immunodeficiency virus type
      1 infection.
AB  - BACKGROUND: Immune function is highly dependent on nutritional status because the
      large mass and high rate of cellular turnover of the immune system make it a
      major user of nutrients. Furthermore, nutrient requirements may be increased
      during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The
      current study was designed to assess relations among HIV-1 progression and 11
      nutritional and demographic variables. DESIGN: The participants were 106 HIV
      infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women;
      age range: 35-57 y). The HIV-infected subjects represented a broad range of
      disease progression. RESULTS: We found lower concentrations of plasma and
      erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in
      the course of HIV-1 infection. Significantly decreased hematocrit and increased
      serum copper concentration developed only late in the course of the disease.
      Statistically significant univariate associations were found between the CD4(+) T
      lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc
      concentration. The lowest erythrocyte magnesium concentrations occurred in HIV
      infected subjects who consumed alcoholic beverages. Independent variables that
      were significant joint predictors of CD4(+) cell count in multiple regression
      analyses were hematocrit and plasma free choline and zinc concentrations. These 3
      factors together explained 43% of the variability in CD4(+) cell counts.
      CONCLUSION: The results provide evidence that compromised nutritional and
      antioxidant status begin early in the course of HIV-1 infection and may
      contribute to disease progression.

PMID- 10966905
TI  - Aging: a barrier to renutrition? Nutritional and immunologic evidence in rats.
AB  - BACKGROUND: Previous reports suggest that correcting the malnourished state is
      more difficult in elderly people than in younger ones and that protein
      requirements may be higher in elderly than in younger adults. OBJECTIVE: The aim
      of this study was to establish whether malnourished old rats respond to protein
      supplemented nutritional repletion as do young adult rats. DESIGN: Adult (3 mo
      old) and old (22 mo old) rats were submitted to dietary restriction programs that
      induced similar metabolic and nutritional alterations. Malnourished adult and old
      rats were then killed (R groups) or refed for 1 wk with a high-protein diet (HPD;
      23% protein) or a very-high-protein diet (VHPD; 27% protein). Control groups at
      both ages were fed ad libitum throughout the experiment. Effects of food
      repletion were evaluated in terms of protein metabolism, intestinal
      histomorphometry, and nonspecific immune status. RESULTS: In adult rats, HPD
      sufficed to increase body weight and restore basal values of liver weight and
      protein content (P: < 0.01 compared with the R adult group), nitrogen balance (P:
      < 0.01 compared with the R adult group), and hydrogen peroxide production by
      polymorphonuclear neutrophils and monocytes (P: < 0.01 compared with the R
      group); VHPD had no supplementary effect except on nitrogen balance. In old rats,
      HPD was less effective and greater benefit was observed with VHPD in terms of
      body weight gain (10%; P: < 0.01 compared with the old group fed HPD),
      albuminemia, muscle weight and protein content, plasma arginine concentration,
      and hydrogen peroxide production by stimulated polymorphonuclear neutrophils and
      monocytes compared with the old R group (P: < 0.01). CONCLUSION: Aging is a
      significant variable affecting the response to nutritional support.

PMID- 10966906
TI  - Cognitive performance is associated with glucose regulation in healthy elderly
      persons and can be enhanced with glucose and dietary carbohydrates.
AB  - BACKGROUND: A glucose drink has been shown to improve memory in persons with poor
      glucose regulation and poor cognition. OBJECTIVE: The objective of this study was
      to determine 1) whether an association between cognition and glucose regulation
      is apparent in healthy seniors and 2) the effects of dietary carbohydrates on
      cognition. DESIGN: After an overnight fast, 10 men and 10 women (aged 60-82 y)
      consumed 50 g carbohydrate as glucose, potatoes, or barley or a placebo on 4
      separate mornings. Cognitive tests were administered 15, 60, and 105 min after
      ingestion of the carbohydrate. Plasma glucose and serum insulin were measured.
      RESULTS: In a multiple regression analysis, poor baseline (placebo) verbal
      declarative memory (immediate and 20-min delayed paragraph recall and word list
      recall) and visuomotor task performance were predicted by poor beta cell
      function, high incremental area under the glucose curve, low insulin resistance,
      and low body mass index. The difference in plasma glucose after food consumption
      [glucose > potatoes > barley > placebo (P: < 0.03)] did not predict performance.
      Although overall performance did not differ with consumption of the different
      test foods, baseline score and beta cell function correlated with improvements in
      immediate and delayed paragraph recall for all 3 carbohydrates (compared with
      placebo); the poorer the baseline memory or beta cell function, the greater the
      improvement (correlation between beta cell function and improvement in delayed
      paragraph recall: r > -0.50, P: < 0.03). Poor beta cell function correlated with
      improvement for all carbohydrates in visuomotor task performance but not on an
      attention task. CONCLUSIONS: Glucose regulation was associated with cognitive
      performance in elderly subjects with normal glucose tolerance. Dietary
      carbohydrates (potatoes and barley) enhanced cognition in subjects with poor
      memories or beta cell function independently of plasma glucose.

PMID- 10966907
TI  - Influence of cognitive eating restraint on total-body measurements of bone
      mineral density and bone mineral content in premenopausal women aged 18-45 y: a
      cross-sectional study.
AB  - BACKGROUND: We examined the relation between cognitive eating restraint (CER) and
      total-body measurements of bone mineral density (BMD) and bone mineral content
      (BMC). OBJECTIVE: Our objective was to determine whether women with CER had lower
      total-body BMD and BMC than did other women. DESIGN: Premenopausal women, 90-150%
      of ideal weight, had measurements of their BMD and BMC made and completed
      questionnaires on physical activity, weight history, body size satisfaction,
      dieting history, eating behavior, and childbearing history. Bone measurements
      were examined for differences between groups with low and high CER scores by
      using analysis of covariance and quartiles of body weight to adjust for body size
      differences. CER was assessed by using the Three-Factor Eating Inventory and was
      defined as a score > or =9; normal eating restraint (NER) was defined by a score
      <9. Total-body BMC, BMD, and fat and lean masses were measured by dual-energy X
      ray absorptiometry. RESULTS: Fifty-two percent of the women were classified as
      having CER. Women with CER were significantly more dissatisfied with their
      bodies. Analysis of covariance, with weight as the covariate, indicated a
      significant difference in BMC between women in preplanned pairs from the 5 lowest
      and 5 highest CER levels. No significant differences in BMD were observed between
      groups. Significantly lower BMC was found in women with high CER scores and body
      weights <71 kg than in those with high CER scores and weights > or =71 kg.
      CONCLUSIONS: BMC was significantly differently between women with low and high
      CER scores. BMC was significantly lower in women with body weights <71 kg and
      classified with CER. Lower BMC in women with high CER scores may indicate an
      increased risk of osteoporosis.

PMID- 10966908
TI  - Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of
      perimenopausal women.
AB  - BACKGROUND: No published studies have directly examined the effect of soy protein
      with isoflavones on bone or bone turnover in perimenopausal women. OBJECTIVE: Our
      objective was to determine the effects of 24 wk of consumption of soy protein
      isolate with isoflavones (80.4 mg/d) in attenuating bone loss during the
      menopausal transition. DESIGN: Perimenopausal subjects were randomly assigned,
      double blind, to treatment: isoflavone-rich soy (SPI+; n = 24), isoflavone-poor
      soy (SPI-; n = 24), or whey (control; n = 21) protein. At baseline and
      posttreatment, lumbar spine bone mineral density (BMD) and bone mineral content
      (BMC) were measured by using dual-energy X-ray absorptiometry. At baseline,
      midtreatment, and posttreatment, urinary N:-telopeptides and serum bone-specific
      alkaline phosphatase (BAP) were measured. RESULTS: The percentage change in
      lumbar spine BMD and BMC, respectively, did not differ from zero in the SPI+ or
      SPI- groups, but loss occurred in the control group (-1.28%, P: = 0.0041; -1.73%,
      P: = 0.0037). By regression analysis, SPI+ treatment had a positive effect on
      change in BMD (5.6%; P: = 0.023) and BMC (10.1%; P: = 0.0032). Baseline BMD and
      BMC (P: < or = 0.0001) negatively affected the percentage change in their
      respective models; baseline body weight (P: = 0.0036) and bone-free lean weight
      (P: = 0.016) contributed positively to percentage change in BMD and BMC,
      respectively. Serum BAP posttreatment was negatively related to percentage change
      in BMD (P: = 0.0016) and BMC (P: = 0.019). Contrast coding using analyses of
      covariance with BMD or BMC as the outcome showed that isoflavones, not soy
      protein, exerted the effect. CONCLUSION: Soy isoflavones attenuated bone loss
      from the lumbar spine in perimenopausal women.

PMID- 10966909
TI  - Fatty diets are unhealthy--even those based on monounsaturates.

PMID- 10966910
TI  - Olive oil: more than just oleic acid.

PMID- 10966913
TI  - All cereals may not be equal.

PMID- 10966915
TI  - Getting nutrition education into medical schools: a computer-based approach.
AB  - Despite awareness of the importance of nutrition as part of medical student's
      education, numerous barriers exist to incorporating nutrition education into the
      medical school curriculum. Chief among such barriers is that most medical schools
      do not have faculty trained specifically in nutrition. A curriculum is needed
      that can deliver comprehensive nutrition information that is consistent across
      medical schools. One way to deliver this information is to use computer-assisted
      instruction (CAI). To meet the different needs of medical schools and provide a
      consistent base of nutrition information, we developed a series of interactive,
      multimedia educational programs (Nutrition in Medicine) that teach the basic
      principles of nutritional science and apply those principles in a case-oriented
      approach. Curriculum content is derived from the American Society for Clinical
      Nutrition consensus guidelines. These modules offer the advantages of
      accessibility, self-paced study, interactivity, immediate feedback, and tracking
      of student performance. Modules are distributed free to all US medical schools.
      Preliminary data from surveys gathered by our team at the University of North
      Carolina at Chapel Hill indicate that 73 US medical schools use, or are planning
      to use, these modules; more schools are currently evaluating the programs.
      Successful implementation of CAI requires easy program access, faculty training,
      adequate technical support, and faculty commitment to the programs as a valuable
      resource. CAI fails when the program is just placed in the library and students
      are told to use it when they can find the time.

PMID- 10966916
TI  - Enhancing nutrition education through faculty development: from workshops to Web
      sites.
AB  - Faculty resistance to changing medical school curricula is a major barrier to
      overcome in the effort to expand nutrition education. With clinical clerkships
      becoming more decentralized and basic science courses utilizing more small group
      teaching, the problem of reform is compounded by the increasing numbers of a more
      dispersed teaching faculty. A faculty development program was designed to
      complement a thematic approach to the inclusion of nutrition in a 4-y curriculum.
      The program offers workshops to help faculty learn how to teach in new settings
      while acquiring new knowledge about nutrition. Additionally, a themes Web site
      offers a window that faculty may use to review current nutrition content, to plan
      their teaching agendas, and to continually reassess where nutrition fits in the
      curriculum.

PMID- 10966917
TI  - Integrating nutrition as a theme throughout the medical school curriculum.
AB  - More than one-third of adult Americans are obese. A major portion of the diseases
      that cause the highest morbidity and mortality, eg, heart disease, cancer,
      diabetes, stroke, and hypertension, can be attributed to diet. Yet, despite the
      demand for more nutrition education, few medical schools have an adequate
      nutrition curriculum. Many medical schools are reducing the number of lecture
      hours in favor of problem-based tutorial discussions, so an addition of another
      mandatory lecture course is not likely. The organization of nutrition as a theme
      throughout the 4-y medical school curriculum can pull together many hours of
      nutrition information taught during various courses, eg, biochemistry,
      physiology, pathophysiology, clinical clerkships, and electives. Emphasis should
      be placed on the identification of available resources (eg, faculty throughout
      the medical school and affiliated hospitals, textbooks, research, and clinical
      experiences) and applied to practical clinical situations so that students are
      able to identify, assess, and appropriately manage the frequent nutritional
      problems seen in outpatients and inpatients. Strategies and techniques such as
      curriculum analysis, computer-aided instruction modules, Internet Web sites, case
      based tutorial discussions, use of physician nutrition specialists and
      dietitians, administratively separate nutrition units, observed structured
      clinical examinations, and faculty development are listed and discussed in this
      article.

PMID- 10966918
TI  - Development of a case-based integrated nutrition curriculum for medical students.
AB  - The Nutrition Education and Prevention Program at the University of Pennsylvania
      School of Medicine is a successful program that can be used as a model for the
      development and implementation of a case-based nutrition curriculum across the 4
      y medical school experience. This article gives a broad overview of the
      development, implementation, evaluation, and dissemination processes used by the
      Nutrition Education and Prevention Program administration and core faculty group
      at the University of Pennsylvania School of Medicine. Beginning in 1990, the
      nutrition curriculum was initiated with the assistance of several funding
      sources. The program was structured using a multidisciplinary faculty group of
      physicians and registered dietitians from multiple departments, centers, and
      institutes. The outcome of this process is a textbook, Medical Nutrition and
      Disease, currently required by numerous medical schools, residency programs, and
      other health professional programs across the nation. With the use of data from
      the Association of American Medical Colleges All Schools Survey of Graduating
      Medical Students, perceptions of the adequacy of nutrition education were tracked
      over time. In 1991, 80% of University of Pennsylvania medical students felt that
      nutrition coverage was inadequate compared with 10% of medical students in 1998,
      a significant change resulting from the nutrition program's effect. The
      University of Pennsylvania School of Medicine has developed and implemented a
      successful nutrition curriculum, despite national trends. The case-based
      integrated curricular model presented in Medical Nutrition and Disease and on our
      Web site, www.med.upenn.edu/nutrimed, can be used by medical institutions and
      other health professionals.

PMID- 10966919
TI  - Signal complex regulation of renal transport proteins: NHERF and regulation of
      NHE3 by PKA.
AB  - The activity of the sodium/hydrogen exchanger 3 (NHE3) isoform of the
      sodium/hydrogen exchanger in the brush-border membrane of the renal proximal
      tubule is tightly regulated. Recent biochemical and cellular experiments have
      established the essential requirement for a new class of regulatory factors,
      sodium/hydrogen exchanger regulatory factor (NHERF) and NHERF-like proteins, in
      cAMP-mediated inhibition of NHE3 activity. NHERF is the first PSD-95/Dlg/ZO-1
      (PDZ) motif-containing protein localized to apical membranes and appears to
      facilitate cAMP-dependent protein kinase A (PKA) phosphorylation of NHE3 by
      interacting with the cytoskeleton to target a multiprotein complex to the brush
      border membrane. Other recent experiments have indicated that NHERF also
      regulates the activity of other renal transport proteins, suggesting that the
      signal complex model of signal transduction in the kidney may be more common than
      presently appreciated. This article reviews studies on the regulation of NHE3 by
      NHERF, PKA, and ezrin and introduces the concept of regulation of renal
      transporters by signal complexes. Although not the primary focus of this review,
      recent studies have indicated a role for NHERF in membrane targeting,
      trafficking, and sorting of transporters, receptors, and signaling proteins. Thus
      NHERF and related PDZ-containing proteins appear to be essential adapters for
      regulation of renal transporters in the mammalian kidney that maintain salt and
      water balance.

PMID- 10966920
TI  - Tissue specificity and physiological relevance of various isoforms of adenylyl
      cyclase.
AB  - The present review focuses on the potential physiological regulations involving
      different isoforms of adenylyl cyclase (AC), the enzymatic activity responsible
      for the synthesis of cAMP from ATP. Depending on the properties and the relative
      level of the isoforms expressed in a tissue or a cell type at a specific time,
      extracellular signals received by the G protein-coupled receptors can be
      differently integrated. We report here on various aspects of such regulations,
      emphasizing the role of Ca(2+)/calmodulin in activating AC1 and AC8 in the
      central nervous system, the potential inhibitory effect of Ca(2+) on AC5 and AC6,
      and the changes in the expression pattern of the isoforms during development. A
      particular emphasis is given to the role of cAMP during drug dependence. Present
      experimental limitations are also underlined (pitfalls in the interpretation of
      cellular transfection, scarcity of the invalidation models, and so on).

PMID- 10966921
TI  - Differential localization of human nongastric H(+)-K(+)-ATPase ATP1AL1 in
      polarized renal epithelial cells.
AB  - The human H(+)-K(+)-ATPase, ATP1AL1, belongs to the subgroup of nongastric, K(+)
      transporting ATPases. In concert with the structurally related gastric H(+)-K(+)
      ATPase, it plays a major role in K(+) reabsorption in various tissues, including
      colon and kidney. Physiological and immunocytochemical data suggest that the
      functional heteromeric ion pumps are usually found in the apical plasma membranes
      of renal epithelial cells. However, the low expression levels of characteristic
      nongastric ion pumps makes it difficult to verify their spatial distribution in
      vivo. To investigate the sorting behavior of ATP1AL1, we expressed this pump by
      stable transfection in MDCK and LLC-PK(1) renal epithelial cell lines. Stable
      interaction of ATP1AL1 with either the endogenous Na(+)-K(+)-ATPase beta-subunit
      or the gastric H(+)-K(+)-ATPase beta-subunit was tested by confocal
      immunofluorescence microscopy and surface biotinylation. In cells transfected
      with ATP1AL1 alone, the alpha-subunit accumulated intracellularly, consistent
      with its inability to assemble and travel to the plasma membrane with the
      endogenous Na(+)-K(+)-ATPase beta-subunit. Cotransfection of ATP1AL1 with the
      gastric H(+)-K(+)-ATPase beta-subunit resulted in plasma membrane localization of
      both pump subunits. In cotransfected MDCK cells the heteromeric ion pump was
      predominantly polarized to the apical plasma membrane. Functional expression of
      ATP1AL1 was confirmed by (86)Rb(+) uptake measurements. In contrast,
      cotransfected LLC-PK(1) cells accumulate ATP1AL1 at the lateral membrane. The
      distinct polarization of ATP1AL1 indicates that the alpha-subunit encodes sorting
      information that is differently interpreted by cell type-specific sorting
      mechanisms.

PMID- 10966922
TI  - Identification of a novel kidney-specific gene downregulated in acute ischemic
      renal failure.
AB  - To gain further insights into the molecular mechanisms involved in acute renal
      failure, we have isolated a new gene from rat and human, named KSP32 (kidney
      specific protein with a molecular mass of 32 kDa). KSP32 encodes a novel gene
      that shows little homology to other mammalian proteins. It, however, shares
      extensive homology with several proteins found in the nematode Caenorhabditis
      elegans and plants. The expression of KSP32 mRNA is highly restricted to kidney.
      In situ hybidization analysis revealed that the expression of KSP32 mRNA was
      prominent in the boundary of kidney cortex and outer medulla, exhibiting a
      raylike formation extending from the medulla into the cortex. Finally, KSP32 mRNA
      was dramatically downregulated in rat following induction of acute ischemic renal
      failure. Rapid loss of KSP32 mRNA expression was observed beginning at
      approximately 5 h following renal injury and mRNA levels remained depressed for
      at least 96 h. Both KSP32 mRNA levels as well as renal function recovered 14 days
      after injury. Administration of an endothelin receptor antagonist (SB-209670),
      known to restore renal function, significantly increased KSP32 expression.

PMID- 10966923
TI  - A functional angiotensin II receptor-GFP fusion protein: evidence for agonist
      dependent nuclear translocation.
AB  - We constructed an expression vector for a fusion protein [ANG II type 1a receptor
      green fluorescent protein (AT(1a)R-GFP)] consisting of enhanced GFP attached to
      the COOH terminus of the rat AT(1a)R. Chinese hamster ovary (CHO) cells
      transfected with AT(1a)R-GFP demonstrated specific, high-affinity (125)I-labeled
      ANG II binding (IC(50) 21 nM). ANG II exposure stimulated sodium-proton exchange
      and cytoplasmic calcium release to a similar extent in cells transfected with
      AT(1a)R or AT(1a)R-GFP; these responses were desensitized by prior exposure to
      ANG II and were sensitive to the AT(1)R blocker losartan. ANG II-driven
      internalization of AT(1a)R-GFP in transfected CHO cells was demonstrated both by
      radioligand binding and by laser scanning confocal microscopy. Colocalization of
      GFP fluorescence with that of the nuclear stain TOTO-3 in confocal images was
      increased more than twofold after 1 h of ANG II exposure. We conclude that
      AT(1a)R-GFP exhibits similar pharmacological behavior to that of the native
      AT(1a)R. Our observations also support previous evidence for the presence of
      AT(1a)R in the nucleus and suggest that the density of AT(1a)R in the nucleus may
      be regulated by exposure to its ligand.

PMID- 10966924
TI  - Structure, function, and regional distribution of the organic cation transporter
      OCT3 in the kidney.
AB  - We examined in this study the expression of the potential-sensitive organic
      cation transporter OCT3 in the kidney. A functionally active OCT3 was cloned from
      a mouse kidney cDNA library. The cloned transporter was found to be capable of
      mediating potential-dependent transport of a variety of organic cations including
      tetraethylammonium. This function was confirmed in two different heterologous
      expression systems involving mammalian cells and Xenopus laevis oocytes. We have
      also isolated the mouse OCT3 gene and deduced its structure and organization. The
      OCT3 gene consists of 11 exons and 10 introns. In situ hybridization studies in
      the mouse kidney have shown that OCT3 mRNA is expressed primarily in the cortex.
      The expression is evident in the proximal and distal convoluted tubules. The
      expression of OCT3 in human kidney was confirmed by RT-PCR. We have also cloned
      OCT3 from human placenta and human kidney. Human OCT3 exhibits 86% identity with
      mouse OCT3 in amino acid sequence. Human OCT3 was found to transport
      tetraethylammonium and a variety of other organic cations. The transport process
      was electrogenic. We conclude that OCT3 is expressed in mammalian kidney and that
      it plays an important role in the renal clearance of cationic drugs.

PMID- 10966925
TI  - Long-term regulation of renal Na-dependent cotransporters and ENaC: response to
      altered acid-base intake.
AB  - Increased systemic acid intake is associated with an increase in apical Na/H
      exchange in the renal proximal tubule mediated by the type 3 Na/H exchanger
      (NHE3). Because NHE3 mediates both proton secretion and Na absorption, increased
      NHE3 activity could inappropriately perturb Na balance unless there are
      compensatory changes in Na handling. In this study, we use semiquantitative
      immunoblotting of rat kidneys to investigate whether acid loading is associated
      with compensatory decreases in the abundance of renal tubule Na transporters
      other than NHE3. Long-term (i.e., 7-day) acid loading with NH(4)Cl produced large
      decreases in the abundances of the thiazide-sensitive Na-Cl cotransporter
      (TSC/NCC) of the distal convoluted tubule and both the beta- and gamma-subunits
      of the amiloride-sensitive epithelial Na channel (ENaC) of the collecting duct.
      In addition, the renal cortical abundance of the proximal type 2 Na-dependent
      phosphate transporter (NaPi-2) was markedly decreased. In contrast, abundances of
      the bumetanide-sensitive Na-K-2Cl cotransporter of the thick ascending limb and
      the alpha-subunit of ENaC were unchanged. A similar profile of changes was seen
      with short-term (16-h) acid loading. Long-term (7-day) base loading with NaHCO(3)
      resulted in the opposite pattern of response with marked increases in the
      abundances of the beta- and gamma-subunits of ENaC and NaPi-2. These adaptations
      may play critical roles in the maintenance in Na balance when changes in acid
      base balance occur.

PMID- 10966926
TI  - Inner medullary lactate production and accumulation: a vasa recta model.
AB  - Since anaerobic glycolysis yields two lactates for each glucose consumed and
      since it is reported to be a major source of ATP for inner medullary (IM) cell
      maintenance, it is a likely source of "external" IM osmoles. It has long been
      known that such an osmole source could theoretically contribute to the "single
      effect" of the urine concentrating mechanism, but there was previously no
      suggestion of a plausible source. I used numerical simulation to estimate axial
      gradients of lactate and glucose that might be accumulated by countercurrent
      recycling in IM vasa recta (IMVR). Based on measurements in other tissues,
      anaerobic glycolysis (assumed to be independent of diuretic state) was estimated
      to consume approximately 20% of the glucose delivered to the IM. IM tissue mass
      and axial distribution of loops and vasa recta were according to reported values
      for rat and other rodents. Lactate (P(LAC)) and glucose (P(GLU)) permeabilities
      were varied over a range of plausible values. The model results suggest that
      P(LAC) of 100 x 10(-5) cm/s (similar to measured permeabilities for other small
      solutes) is sufficiently high to ensure efficient lactate recycling. By contrast,
      it was necessary in the model to reduce P(GLU) to a small fraction of this value
      (1/25th) to avoid papillary glucose depletion by countercurrent shunting. The
      results predict that IM lactate production could suffice to build a significant
      steady-state axial lactate gradient in the IM interstitium. Other modeling
      studies (Jen JF and Stephenson JL. Bull Math Biol 56: 491-514, 1994; and Thomas
      SR and Wexler AS. Am J Physiol Renal Fluid Electrolyte Physiol 269: F159-F171,
      1995) have shown that 20-100 mosmol/kgH(2)O of unspecified external,
      interstitial, osmolytes could greatly improve IM concentrating ability. The
      present study gives several plausible scenarios consistent with accumulation of
      metabolically produced lactate osmoles, although only to the lower end of this
      range. For example, if 20% of entering glucose is consumed, the model predicts
      that papillary lactate would attain about 15 mM assuming vasa recta outflow is
      increased 30% by fluid absorbed from the nephrons and collecting ducts and that
      this lactate gradient would double if IM blood flow were reduced by one-half, as
      may occur in antidiuresis. Several experimental tests of the hypothesis are
      indicated.

PMID- 10966927
TI  - Molecular cloning, chromosomal organization, and functional characterization of a
      sodium-dicarboxylate cotransporter from mouse kidney.
AB  - The sodium-dicarboxylate cotransporter of the renal proximal tubule, NaDC-1,
      reabsorbs filtered Krebs cycle intermediates and plays an important role in the
      regulation of urinary citrate concentrations. (1) Low urinary citrate is a risk
      factor for the development of kidney stones. As an initial step in the
      characterization of NaDC-1 regulation, the genomic structure and functional
      properties of the mouse Na(+)-dicarboxylate cotransporter (mNaDC-1) were
      determined. The gene coding for mNaDC-1, Slc13a2, is found on chromosome 11. The
      gene is approximately 24.9 kb in length and contains 12 exons. The mRNA coding
      for mNaDC-1 is found in kidney and small intestine. Expression of mNaDC-1 in
      Xenopus laevis oocytes results in increased transport of di- and tricarboxylates.
      The Michaelis-Menten constant (K(m)) for succinate was 0.35 mM, and the K(m) for
      citrate was 0.6 mM. The transport of citrate was stimulated by acidic pH, whereas
      the transport of succinate was insensitive to pH changes. Transport by mNaDC-1 is
      electrogenic, and substrates produced inward currents in the presence of sodium.
      The sodium affinity was relatively high in mNaDC-1, with half-saturation
      constants for sodium of 10 mM (radiotracer experiments) and 28 mM at -50 mV (2
      electrode voltage clamp experiments). Lithium acts as a potent inhibitor of
      transport, but it can also partially substitute for sodium. In conclusion, the
      mNaDC-1 is related in sequence and function to the other NaDC-1 orthologs.
      However, its function more closely resembles the rabbit and human orthologs
      rather than the rat NaDC-1, with which it shares higher sequence similarity.

PMID- 10966928
TI  - Chaotic behavior of renal sympathetic nerve activity: effect of baroreceptor
      denervation and cardiac failure.
AB  - Nonlinear dynamic analysis was used to examine the chaotic behavior of renal
      sympathetic nerve activity in conscious rats subjected to either complete
      baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation) or
      induction of congestive heart failure (CHF). The peak interval sequence of
      synchronized renal sympathetic nerve discharge was extracted and used for
      analysis. In control rats, this yielded a system whose correlation dimension
      converged to a low value over the embedding dimension range of 10-15 and whose
      greatest Lyapunov exponent was positive. Complete baroreceptor denervation was
      associated with a decrease in the correlation dimension of the system (before
      2.65 +/- 0.27, after 1.64 +/- 0.17; P < 0.01) and a reduction in chaotic behavior
      (greatest Lyapunov exponent: 0.201 +/- 0.008 bits/data point before, 0.177 +/-
      0.004 bits/data point after, P < 0.02). CHF, a state characterized by impaired
      sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve
      activity, was associated with a similar decrease in the correlation dimension
      (control 3.41 +/- 0.23, CHF 2.62 +/- 0.26; P < 0.01) and a reduction in chaotic
      behavior (greatest Lyapunov exponent: 0.205 +/- 0.048 bits/data point control,
      0.136 +/- 0.033 bits/data point CHF, P < 0.02). These results indicate that
      removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic
      nerve activity, occurring either physiologically or pathophysiologically, is
      associated with a decrease in the correlation dimensions of the system and a
      reduction in chaotic behavior.

PMID- 10966929
TI  - Vasopressin-dependent upregulation of aquaporin-2 gene expression in
      glucocorticoid-deficient rats.
AB  - We determined alterations in renal aquaporin-2 (AQP2) gene expression in
      association with impaired water excretion in glucocorticoid-deficient rats. After
      adrenalectomy, Sprague-Dawley rats were administered aldosterone alone by osmotic
      pumps (glucocorticoid-deficient rats). As a control, both aldosterone and
      dexamethasone were administered. These animals were subjected to the studies on
      days 7-14. The expressions of AQP2 mRNA and protein in kidney of the
      glucocorticoid-deficient rats were increased by 1.6- and 1.4-fold compared with
      the control rats, respectively. An acute oral water load test verified the marked
      impairment in water excretion in the glucocorticoid-deficient rats. One hour
      after the water load, the expressions of AQP2 mRNA and protein were significantly
      reduced in the control rats, but they remained unchanged in the glucocorticoid
      deficient rats. However, there was no alteration in [(3)H]arginine vasopressin
      (AVP) receptor binding and AVP V(2) receptor mRNA expression in the
      glucocorticoid-deficient rats. A V(2)-receptor antagonist abolished the increased
      expressions of AQP2 mRNA and protein in the glucocorticoid-deficient rats. These
      results indicate that augmented expression of AQP2 participates in impaired water
      excretion, dependent on AVP, in glucocorticoid deficiency.

PMID- 10966930
TI  - Downregulation of the calpain inhibitor protein calpastatin by caspases during
      renal ischemia-reperfusion.
AB  - The interaction between the cysteine proteases calpain and caspases during renal
      ischemia-reperfusion (I/R) was investigated. An increase in the activity of
      calpain, as determined by 1) the appearance of calpain-mediated spectrin
      breakdown products and 2) the conversion of procalpain to active calpain, was
      demonstrated. Because intracellular calpain activity is regulated by calpastatin,
      the effect of I/R on calpastatin was determined. On immunoblot of renal cortex,
      there was a 50-100% decrease of a low molecular weight (LMW) form of calpastatin
      (41 kDa) after I/R. Calpastatin activity was also significantly decreased after
      I/R compared with sham-operated rats, indicating that the decreased protein
      expression had functional significance. In rats treated with the caspase
      inhibitor, z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-D-DCB), the decrease in
      both calpastatin activity and protein expression was normalized, suggesting that
      caspases may be proteolyzing calpastatin. Caspase 3 activity increased
      significantly after I/R and was attenuated in ischemic kidneys from rats treated
      with the caspase inhibitor. In summary, during renal I/R injury, there is 1)
      calpain activation associated with downregulation of calpastatin protein and
      decreased calpastatin activity and 2) activation of caspase 3. In addition, in
      vivo caspase inhibition reverses the decrease in calpastatin activity. In
      conclusion, proteolysis of calpastatin by caspase 3 may regulate calpain activity
      during I/R injury. Although the protective effect of cysteine protease inhibition
      against hypoxic necrosis of proximal tubules has previously been demonstrated,
      the functional significance in ischemic acute renal failure in vivo merits
      further study.

PMID- 10966931
TI  - Defective fluid and HCO(3)(-) absorption in proximal tubule of neuronal nitric
      oxide synthase-knockout mice.
AB  - Using renal clearance techniques and in situ microperfusion of proximal tubules,
      we examined the effects of N(G)-monomethyl-L-arginine methyl ester (L-NAME) on
      fluid and HCO(3)(-) transport in wild-type mice and also investigated proximal
      tubule transport in neuronal nitric oxide synthase (nNOS)-knockout mice. In wild
      type mice, administration of L-NAME (3 mg/kg bolus iv) significantly increased
      mean blood pressure, urine volume, and urinary Na(+) excretion. L-NAME, given by
      intravenous bolus and added to the luminal perfusion solution, decreased
      absorption of fluid (60%) and HCO(3)(-) (49%) in the proximal tubule. In nNOS
      knockout mice, the urinary excretion of HCO(3)(-) was significantly higher than
      in the wild-type mice (3.12 +/- 0.52 vs. 1. 40 +/- 0.33 mM) and the rates of
      HCO(3)(-) and fluid absorption were 62 and 72% lower, respectively. Both arterial
      blood HCO(3)(-) concentration (20.7 vs. 25.7 mM) and blood pH (7.27 vs. 7.34)
      were lower, indicating a significant metabolic acidosis in nNOS-knockout mice.
      Blood pressure was lower in nNOS-knockout mice (76.2 +/- 4.6 mmHg) than in wild
      type control animals (102.9 +/- 8.4 mmHg); however, it increased in response to L
      NAME (125.5 +/- 5.07 mmHg). Plasma Na(+) and K(+) were not significantly
      different from control values. Our data show that a large component of HCO(3)(-)
      and fluid absorption in the proximal tubule is controlled by nNOS. Mice without
      this isozyme are defective in absorption of fluid and HCO(3)(-) in the proximal
      tubule and develop metabolic acidosis, suggesting that nNOS plays an important
      role in the regulation of acid-base balance.

PMID- 10966932
TI  - Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in
      mice.
AB  - Mononuclear cell infiltrates are found in human renal ischemia-reperfusion injury
      (IRI), and peritubular T lymphocytes have been identified in experimental IRI.
      However, the role of T cells in the pathogenesis of renal IRI is unknown. We
      hypothesized that T cells are one of the important mediators of renal IRI. To
      test this hypothesis, we used an established mouse model of renal IRI, and
      evaluated mice with genetically engineered deficiency of both CD4+ and CD8+ T
      cells. At 48 h postischemia, CD4/CD8-knockout (KO) mice had marked improvement in
      renal function compared with control C57BL/6 mice (serum creatinine: 0.7 +/- 0.4
      vs. 2.5 +/- 0.3 mg/dl, respectively; P < 0.05). Neutrophil infiltration into
      postischemic kidney was reduced in CD4/CD8 KO mice, compared with control mice,
      at both 24 h [polymorphonuclear neutrophils (PMNs)/10 high power fields: 714 +/-
      354 vs. 3,514 +/- 660, respectively; P < 0.05] and 48 h (88 +/- 32 vs. 1,979 +/-
      209, respectively; P < 0.05). Tubular necrosis score in CD4/CD8 KO mice, compared
      with control mice, was significantly less at 48 h (0.4 +/- 0.1 vs. 2.4 +/- 0.2,
      respectively; P < 0.05). Because adhesion between T cells and renal tubular
      epithelial cells (RTECs) may underlie the pathophysiological role of T cells in
      renal IRI, we also measured T cell adhesion to primary murine RTECs in vitro.
      Exposure of RTECs to 2 h of hypoxia followed by 1 h of reoxygenation increased T
      cell adhesion more than twofold. Phorbol ester treatment, which activates
      integrins, increased T cell adhesion threefold. These data suggest that T
      lymphocytes can mediate experimental renal IRI. Moreover, adhesion of
      infiltrating T cells to renal tubular cells may provide a potential mechanism
      underlying postischemic tubular dysfunction.

PMID- 10966933
TI  - Potassium deprivation upregulates expression of renal basolateral Na(+)-HCO(3)(-)
      cotransporter (NBC-1).
AB  - The purpose of the present experiments was to examine the effect of potassium
      deprivation on the expression of the renal basolateral Na(+)-HCO(3)(-)
      cotransporter (NBC-1). Rats were placed on a K(+)-free diet for various time
      intervals and examined. NBC-1 mRNA levels increased by about threefold in the
      cortex (P < 0.04) at 72 h of K(+) deprivation and remained elevated at 21 days.
      NBC activity increased by approximately 110% in proximal tubule suspensions, with
      the activity increasing from 0.091 in control to 0.205 pH/min in the K(+)
      deprived group (P < 0.005). The inner stripe of outer medulla and cells of
      medullary thick ascending limb of Henle (mTAL) showed induction of NBC-1 mRNA and
      activity in K(+)-deprived rats, with the activity in mTAL increasing from 0.010
      in control to 0.133 pH/min in the K(+)-deprived group (P < 0.004). K(+)
      deprivation also increased NBC-1 mRNA levels in the renal papilla (P < 0.02). We
      conclude that 1) K(+) deprivation increases NBC-1 expression and activity in
      proximal tubule and 2) K(+) deprivation causes induction of NBC-1 expression and
      activity in mTAL tubule and inner medulla. We propose that NBC-1 likely mediates
      enhanced HCO(3)(-) reabsorption in proximal tubule, mTAL, and inner medullary
      collecting duct in K(+) deprivation and contributes to the maintenance of
      metabolic alkalosis in this condition.

PMID- 10966934
TI  - Angiotensin II releases 20-HETE from rat renal microvessels.
AB  - We studied hydroxyeicosatetraenoic acid (HETE) release in response to ANG II from
      preglomerular microvessels (PGMVs), the vascular segment governing changes in
      renal vascular resistance. PGMVs were isolated from Sprague-Dawley rats and
      incubated with NADPH and hormones at 37 degrees C. Eicosanoids were extracted,
      and cytochrome P-450 (CYP)-derived HETEs were purified and quantitated by
      negative chemical ionization gas chromatography-mass spectroscopy. PGMVs produced
      primarily 20- and 19-HETEs, namely, 7.9 +/- 1.7 and 2.2 +/- 0.5 ng/mg protein,
      respectively. ANG II (5 nM) increased CYP-HETE release by two- to threefold;
      bradykinin, phenylephrine, and Ca(2+) ionophore were without effect. [Sar(1)]ANG
      II (0.1-100 microM) dose dependently stimulated 19- and 20-HETEs, an effect
      blocked by the AT(2)-receptor antagonist PD-123319 as well as by U-73122, a
      phospholipase C inhibitor. Microvascular 20-HETE release was increased more than
      twofold by the third day in response to ANG II (120 ng. kg(-1). min(-1)) infused
      subcutaneously for 2 wk; it was not further enhanced after 14 days, although
      blood pressure continued to rise. Thus an AT(2)-phospholipse C effector unit is
      associated with synthesis of a vasoconstrictor product, 20-HETE, in a key
      renovascular segment.

PMID- 10966936
TI  - Mechanism of increases in L-kynurenine and quinolinic acid in renal
      insufficiency.
AB  - Marked increases in metabolites of the L-tryptophan-kynurenine pathway, L
      kynurenine and quinolinic acid (Quin), were observed in serum and cerebrospinal
      fluid (CSF) of both the rat and human with renal insufficiency. The mechanisms
      responsible for their accumulation after renal insufficiency were investigated.
      In patients with chronic renal insufficiency, elevated levels of serum L
      kynurenine and Quin were reduced by hemodialysis. In renal-insufficient rats,
      Quin and L-kynurenine levels in serum, brain, and CSF were also increased
      parallel to the severity of renal insufficiency. Urinary excretion of Quin (3.5
      fold) and L-kynurenine (2.8-fold) was also increased. Liver L-tryptophan 2,3
      dioxygenase activity (TDO), a rate-limiting enzyme of the kynurenine pathway, was
      increased in proportion to blood urea nitrogen and creatinine levels. Kynurenine
      3-hydroxylase and quinolinic acid phosphoribosyltransferase were unchanged, but
      the activities of kynureninase, 3-hydroxyanthranilate dioxygenase, and
      aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) were significantly
      decreased. Systemic administrations of pyrazinamide (ACMSDase inhibitor)
      increased serum Quin concentrations in control rats, demonstrating that changes
      in body ACMSDase activities in response to renal insufficiency are important
      factors for the determination of serum Quin concentrations. We hypothesize the
      following ideas: that increased serum L-kynurenine concentrations are mainly due
      to the increased TDO and decreased kynureninase activities in the liver and
      increased serum Quin concentrations are due to the decreased ACMSDase activities
      in the body after renal insufficiency. The accumulation of CSF L-kynurenine is
      caused by the entry of increased serum L-kynurenine, and the accumulation of CSF
      Quin is secondary to Quin from plasma and/or Quin precursor into the brain.

PMID- 10966935
TI  - Altered expression of renal AQPs and Na(+) transporters in rats with lithium
      induced NDI.
AB  - Lithium (Li) treatment is often associated with nephrogenic diabetes insipidus
      (NDI). The changes in whole kidney expression of aquaporin-1 (AQP1), -2, and -3
      as well as Na-K-ATPase, type 3 Na/H exchanger (NHE3), type 2 Na-Pi cotransporter
      (NaPi-2), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), and
      thiazide-sensitive Na-Cl cotransporter (TSC) were examined in rats treated with
      Li orally for 4 wk: protocol 1, high doses of Li (high Na(+) intake), and
      protocol 2, low doses of Li (identical food and normal Na(+) intake in Li-treated
      and control rats). Both protocols resulted in severe polyuria. Semiquantitative
      immunoblotting revealed that whole kidney abundance of AQP2 was dramatically
      reduced to 6% (protocol 1) and 27% (protocol 2) of control levels. In contrast,
      the abundance of AQP1 was not decreased. Immunoelectron microscopy confirmed the
      dramatic downregulation of AQP2 and AQP3, whereas AQP4 labeling was not reduced.
      Li-treated rats had a marked increase in urinary Na(+) excretion in both
      protocols. However, the expression of several major Na(+) transporters in the
      proximal tubule, loop of Henle, and distal convoluted tubule was unchanged in
      protocol 2, whereas in protocol 1 significantly increased NHE3 and BSC-1
      expression or reduced NaPi-2 expression was associated with chronic Li treatment.
      In conclusion, severe downregulation of AQP2 and AQP3 appears to be important for
      the development of Li-induced polyuria. In contrast, the increased or unchanged
      expression of NHE3, BSC-1, Na-K-ATPase, and TSC indicates that these Na(+)
      transporters do not participate in the development of Li-induced polyuria.

PMID- 10966937
TI  - Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal
      hemodynamic changes in diabetes.
AB  - Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic
      changes in diabetes mellitus. However, the contribution of nitric oxide synthase
      (NOS) isoforms to intrarenal production of NO in diabetes remains unknown. To
      explore the role of NOS1 in the control of renal hemodynamics in diabetes, we
      assessed renal responses to inhibition of NOS1 with S-methyl-L-thiocitrulline
      (SMTC; administered into the abdominal aorta) in moderately hyperglycemic
      streptozotocin-diabetic rats (D) and their nondiabetic (C) and normoglycemic
      diabetic counterparts. The contribution of other NOS isoforms was also evaluated
      by assessing the responses to nonspecific NOS inhibition [N(G)-nitro-L-arginine
      methyl ester (L-NAME)] in SMTC-treated diabetic rats. The number of NOS1-positive
      cells in macula densa of D and C kidneys was also evaluated by
      immunohistochemistry. D rats demonstrated elevated glomerular filtration rate
      (GFR) compared with C. SMTC (0.05 mg/kg) normalized GFR in D but had no effect in
      C. SMTC-induced reduction of renal plasma flow (RPF) was similar in C and D.
      Normoglycemic diabetic rats demonstrated blunted renal hemodynamic responses to
      NOS1 inhibition compared with hyperglycemic animals. Mean arterial pressure was
      stable in all groups. L-NAME induced a further decrease in RPF, but not in GFR,
      in D rats treated with SMTC. Immunohistochemistry revealed increased numbers of
      NOS1-positive cells in D. These observations suggest that NOS1-derived NO plays a
      major role in the pathogenesis of renal hemodynamic changes early in the course
      of diabetes. NOS1 appears to be the most important isoform in the generation of
      hemodynamically active NO in this condition.

PMID- 10966938
TI  - Functional and pharmacological characterization of human Na(+)-carnitine
      cotransporter hOCTN2.
AB  - L-Carnitine is essential for the translocation of acyl-carnitine into the
      mitochondria for beta-oxidation of long-chain fatty acids. It is taken up into
      the cells by the recently cloned Na(+)-driven carnitine organic cation
      transporter OCTN2. Here we expressed hOCTN2 in Xenopus laevis oocytes and
      investigated with two-electrode voltage- clamp and flux measurements its
      functional and pharmacological properties as a Na(+)-carnitine cotransporter. L
      carnitine transport was electrogenic. The L-carnitine-induced currents were
      voltage and Na(+) dependent, with half-maximal currents at 0.3 +/- 0.1 mM Na(+)
      at -60 mV. Furthermore, L-carnitine-induced currents were pH dependent,
      decreasing with acidification. In contrast to other members of the organic cation
      transporter family, hOCTN2 functions as a Na(+)-coupled carnitine transporter.
      Carnitine transport was stereoselective, with an apparent Michaelis-Menten
      constant (K(m)) of 4.8 +/- 0.3 microM for L-carnitine and 98.3 +/- 38.0 microM
      for D-carnitine. The substrate specificity of hOCTN2 differs from rOCT-1 and hOCT
      2 as hOCTN2 showed only small currents with classic OCT substrates such as
      choline or tetraethylammonium; by contrast hOCTN2 mediated transport of betaine.
      hOCTN2 was inhibited by several drugs known to induce secondary carnitine
      deficiency. Most potent blockers were the antibiotic emetine and the ion channel
      blockers quinidine and verapamil. The apparent IC(50) for emetine was 4.2 +/- 1.2
      microM. The anticonvulsant valproic acid did not induce a significant inhibition
      of carnitine transport, pointing to a different mode of action. In summary,
      hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity
      transport of L-carnitine and Na(+). hOCTN2 displays transport properties distinct
      from other members of the OCT family and is directly inhibited by several
      substances known to induce systemic carnitine deficiency.

PMID- 10966939
TI  - Who's afraid of prevention of blindness?

PMID- 10966940
TI  - Amblyopia.

PMID- 10966941
TI  - Age related macular degeneration: could we improve the services we offer?

PMID- 10966942
TI  - Evaluation of a national eye care programme: re-survey after 10 years.
AB  - AIM: To re-survey the Gambia after an interval of 10 years to assess the impact
      of a national eye care programme (NECP) on the prevalence of blindness and low
      vision. METHOD: Comparison of two multistage cluster random sample surveys taking
      into account the marked increase in population in the Gambia, west Africa.
      Samples of the whole population in 1986 and 1996 were taken. The definition of
      blindness is presenting vision less than 3/60 in the better eye, or visual fields
      constricted to less than 10 degrees from fixation. Low vision is less than 6/18
      but 3/60 or better. Causes of blindness were determined clinically by three
      ophthalmologists. RESULTS: The crude prevalence of blindness fell from 0.70% to
      0.42%, a relative reduction of 40%. During the same 10 year period, the
      population increased by 51% from 775 000 to 1 169 000. When the results were
      standardised for age, a west to east gradient was found for changes in risk of
      blindness over the 10 year period. This matched the phased west to east
      introduction of the NECP interventions. There was a modest but significant
      increase in the risk of low vision across the whole country. CONCLUSIONS: The
      overall reduction in risk of blindness, in those areas where the NECP has been
      active, appears to justify the programme and the support of donor organisations.
      The low vision cases due to cataract must now be addressed.

PMID- 10966943
TI  - Amblyopia: is visual loss permanent?
AB  - AIM: To ascertain whether recovery of visual function in amblyopic eyes is likely
      to occur when the fellow eye is lost as a result of age related macular
      degeneration. METHODS: The records of 465 patients with an established diagnosis
      of age related macular degeneration who had attended a specialist macular clinic
      between 1990 and 1998 were scrutinised. A full clinical examination and
      standardised refraction had been carried out in 189 of these cases on a minimum
      of two occasions. Cases were looked for where an improvement of one or more lines
      of either distance or near acuity was recorded in the eye unaffected by macular
      disease. In each one of these cases the improvement in visual acuity could not be
      attributed to treatment of other existing pathology. RESULTS: 12 such cases were
      detected. In nine of these the eye showing improvement of acuity had a history of
      amblyopia. The mean improvement in distance and near acuity in amblyopic eyes by
      12 months was 3.3 and 1.9 lines logMAR respectively. The improvement in acuity
      generally occurred between 1 and 12 months from baseline and remained stable over
      the period of follow up. CONCLUSIONS: Older people with a history of amblyopia
      who develop visual loss in the previously normal eye can experience recovery of
      visual function in the amblyopic eye over a period of time. This recovery in
      visual function occurs in the wake of visual loss in the fellow eye and the
      improvement appears to be sustained.

PMID- 10966944
TI  - Parental non-concordance with occlusion therapy.
AB  - BACKGROUND/AIMS: Non-concordance has often been reported as a major contributor
      to the failure of occlusion therapy for amblyopia. In other fields of medicine
      the extent of a patient's understanding in areas of the disease and treatment has
      been shown to have both a direct and indirect effect on subsequent concordance.
      The aims of this study were to determine the extent of parental non-concordance,
      to assess their level of understanding in key areas of amblyopia, occlusion
      therapy, critical period and prognosis, and to discover the parent's own reasons
      for failing to concord. METHODS: Parents of children aged 2-7 years receiving a
      minimum of 1 hour of occlusion for unilateral amblyopia were recruited. Parental
      concordance was monitored using a diary and their understanding and reasons for
      non-concordance were assessed by a questionnaire. Concordance was analysed by
      calculating a concordance index, determining the proportion of non-concordance,
      and also by classifying the non-concordance on the basis of whether the behaviour
      was intentional or unintentional and whether the parents were adequately or
      inadequately informed. RESULTS: Parental non-concordance was defined as failing
      to occlude less than 80% of the total prescribed time. The median concordance
      index was 0.75 and the proportion of non-concordant parents was 0.54 (95% CI 0.41
      to 0.67) (n = 57). Parental knowledge was poor in areas of the critical period
      with 23% of parents unaware of an age limit to the treatment. Reasons for non
      concordance given by 68% of parents demonstrated poor knowledge. CONCLUSION: A
      substantial proportion of the non-concordant parents had poor understanding in
      areas such as the critical period and errors also occurred in implementing the
      treatment regimen. Increased parental awareness of the rationale and urgency of
      the treatment, with reinforcement of details of the regimen, would help to reduce
      non-concordance with occlusion therapy.

PMID- 10966945
TI  - Long term follow up of premature infants: detection of strabismus, amblyopia, and
      refractive errors.
AB  - AIM: To establish recommendations for long term ophthalmological follow up of
      prematurely born infants. METHODS: 130 infants with a gestational age (GA) <37
      weeks and born between 1 November 1989 and 31 October 1990 were enrolled in a
      prospective study about the development of strabismus, amblyopia, and refractive
      errors. Infants were subdivided in three groups according to GA: A <28 weeks
      (n=32), B >/=28-</=32 weeks (n=64), C >32-<37 weeks (n=34). Ophthalmological
      assessment took place at the postconceptional age of 32 weeks, at term and at 3,
      6, 12, and 30 months post term. At the age of 5 years parents received a
      questionnaire and a majority of the children was examined again (n=99). RESULTS:
      At the age of 5 years 46 infants were known to have strabismus (n=29) and/or
      amblyopia (n=22) and/or refractive errors (n=22). Statistical analysis showed
      that gestational age, duration of supplementary oxygen, and duration of
      hospitalisation were important predictive variables for the development of
      strabismus, amblyopia, or refractive errors (SAR) at the age of 5 years (p<0.05).
      Infants with a GA </=32 weeks had a significantly higher risk of developing SAR
      than infants with a GA >32 weeks, who developed an incidence comparable with the
      normal population. Strabismus developed mainly in the first year of life and at
      the age of 5 years. Most infants with amblyopia were detected at the age of 2-3
      years. Refractive errors were found in the first year of life and at the age of
      2.5 and 5 years. CONCLUSION: Infants with a GA <32 weeks should be selected for
      long term ophthalmological follow up. These infants should be screened at the age
      of 1 year, in the third year of life (preferably at 30 months), and just before
      school age (including testing of visual acuity with optotypes).

PMID- 10966946
TI  - Clinical and epidemiological features of acute follicular conjunctivitis with
      special reference to that caused by herpes simplex virus type 1.
AB  - BACKGROUND/AIMS: It is reported by the national surveillance of ocular infectious
      diseases in Japan that 4.3% of cases of epidemic keratoconjunctivitis (EKC)
      diagnosed clinically were caused by herpes simplex virus (HSV). Clinical and
      virological studies of patients with HSV conjunctivitis were carried out.
      METHODS: The study population consisted of 478 patients with acute follicular
      conjunctivitis. Virological analysis was carried out for adenovirus (Ad) and HSV
      by the cell culture method and fluorescein antibody (FA) method. Polymerase chain
      reaction for Chlamydia trachomatis was also carried out. RESULTS: From 23
      patients, HSV type 1 was isolated but Ad or C trachomatis was not isolated. 87%
      of cases were unilateral. Most cases showed clinical resolution within 9 days.
      Early corneal lesions and preauricular lymphadenopathy were less frequent in HSV
      conjunctivitis than in adenoviral conjunctivitis, especially that due to subgenus
      D. No case showed a positive result for HSV by the FA method using conjunctival
      swabs; however, the FA test was positive in all strains isolated by cell culture.
      CONCLUSIONS: These results indicate that it is difficult clinically to
      differentiate HSV conjunctivitis from adenoviral conjunctivitis in the acute
      stage, since the clinical features of adenoviral conjunctivitis are similar to
      those of HSV conjunctivitis. A biological difference may exist between HSV
      strains causing keratitis and conjunctivitis.

PMID- 10966947
TI  - Amniotic membrane graft for primary pterygium: comparison with conjunctival
      autograft and topical mitomycin C treatment.
AB  - AIM: To study the efficacy and safety of amniotic membrane graft as an adjunctive
      therapy after removal of primary pterygium, and to compare the clinical outcome
      with conjunctival autograft and topical mitomycin C. METHODS: 80 eyes of 71
      patients with primary pterygia were treated with excision followed by amniotic
      membrane graft. The result was compared retrospectively with 56 eyes of 50
      patients receiving conjunctival autograft, and 54 eyes of 46 patients receiving
      topical mitomycin C. Patients were followed for at least 6 months, and the
      averaged follow up periods for the three groups were 13.8, 22.8, and 18.4 months,
      respectively. RESULTS: There were three recurrences (3.8%) in the amniotic
      membrane graft group, three recurrences (5.4%) in the conjunctival autograft
      group, and two recurrences (3.7%) in the topical mitomycin C group. There was no
      significant difference in recurrence rate among the three groups (p = 0.879). No
      major complications occurred in the amniotic membrane graft group or the
      conjunctival autograft group. One case of infectious scleritis due to scleral
      ischaemia occurred in the topical mitomycin C group. CONCLUSION: This study
      showed that amniotic membrane graft was as effective as conjunctival autograft
      and mitomycin C in preventing pterygium recurrence, and can be considered as a
      preferred grafting procedure for primary pterygium.

PMID- 10966948
TI  - Early treatment with cyclosporin in serpiginous choroidopathy maintains remission
      and good visual outcome.
AB  - AIMS: To describe management and clinical outcomes of serpiginous choroidopathy
      treated primarily with cyclosporin at a tertiary uveitis referral centre METHODS:
      A case series of 14 eyes of seven patients with serpiginous choroidopathy with
      follow up ranging from 1.3 to 13 years is described. All patients had fundus
      lesions consistent with serpiginous choroidopathy, were investigated for systemic
      disease, had fluorescein angiography, and were treated with combined
      immunosuppressive therapy including cyclosporin. RESULTS: No patients suffered
      significant loss of acuity after starting systemic immunosuppression with
      cyclosporin as the primary agent. All but one patient achieved remission and were
      able to stop medications with no recurrences in the follow up period. Side
      effects from cyclosporin were well tolerated and there were no serious
      complications from immunosuppression. CONCLUSIONS: Cyclosporin is a safe and
      effective option with which to manage serpiginous choroidopathy. Significantly,
      adequate immunosuppression can result in clinical remission and cessation of
      therapy in some patients.

PMID- 10966949
TI  - Recombinant tissue plasminogen activator following paediatric cataract surgery.
AB  - BACKGROUND: The use of recombinant tissue plasminogen activator (r-TPA) has been
      advocated in the treatment of postsurgical fibrinous membrane formation following
      cataract surgery in adults. Its use in paediatric cases is not well documented.
      METHOD: A retrospective review of paediatric cataract extractions performed at
      Moorfields Eye Hospital between 1 January 1997 and 4 April 1999 was carried out.
      RESULTS: Cataract extractions were performed in 37 patients, 22 in males 15 in
      females. Four (9.2%) underwent intracameral injection of 25 microg r-TPA. They
      were all females of Afro-Caribbean origin. The time to injection varied from 4-14
      days, mean 7.2 days. Complete resolution of the fibrinous membrane was seen in
      all cases. There were no complications by the 3 month follow up. CONCLUSION: r
      TPA may be used safely and effectively at a dose of 25 microg for the treatment
      of severe fibrinous membranes following paediatric cataract extraction. It aided
      the visual recovery of the children and also allowed a reduced regimen of topical
      steroid therapy to be used postoperatively.

PMID- 10966950
TI  - Effect of cataract extraction and posterior chamber lens implantation on outflow
      facility and its response to pilocarpine in Korean subjects.
AB  - AIM: To investigate the effect of the lens on outflow facility in Korean patients
      with cataracts. METHODS: Intraocular pressure was measured by Goldmann
      applanation tonometry in 42 patients with cataracts and outflow facility was
      determined by tonography preoperatively, before and after instillation of
      pilocarpine. All patients received clear corneal phacoemulsification and silicone
      foldable intraocular lens implantation within the capsular bag by one surgeon.
      Two months after surgery, slit lamp examination and gonioscopy were performed and
      intraocular pressure and outflow facility were again determined. Statistical
      analysis was carried out using the Student's paired t test. RESULTS: There were
      no anterior chamber reactions and no visible trabecular meshwork damage 2 months
      after surgery. Intraocular pressure 2 months after lens extraction decreased by a
      mean of 2.4 (SE 0.4) mm Hg (p<0.001) compared with the preoperative value;
      postoperative outflow facility with and without pilocarpine increased by 0.080
      (0.019) microl/min/mm Hg (p<0.001) and 0.045 (0.014) microl/min/mm Hg (p<0.001),
      respectively, at 2 months compared with preoperative values. The facility
      response to pilocarpine after lens extraction, relative to the baseline value and
      preoperative response, increased by 10.7 (7.1)% which was not statistically
      significant (p>0.1). CONCLUSION: Lens extraction causes a reduction in
      intraocular pressure and an increase in outflow facility in Korean subjects.
      Pilocarpine causes an increase in outflow facility which persists after cataract
      extraction and posterior chamber lens implantation.

PMID- 10966951
TI  - Rates of hospital admissions for primary angle closure glaucoma among Chinese,
      Malays, and Indians in Singapore.
AB  - AIM: To estimate the rates of hospital admissions for primary angle closure
      glaucoma (PACG) in Chinese, Malays, and Indians in Singapore METHODS: A
      population-wide hospital discharge database in Singapore was used to identify all
      hospital admissions with a primary discharge diagnosis of PACG (International
      Classification of Disease-CM code: 365.2). The Singapore census was used for
      denominator data. RESULTS: Between 1993 and 1997 there were 894 hospital
      admissions for PACG. The mean annual rate of PACG admissions was 11.1 per 100 000
      (95% confidence interval (CI), 10.4, 11.8) among people aged 30 years and over.
      The annual rate was highest for Chinese (age and sex adjusted rate: 12.2 per 100
      000), which was twice that of Malays (6.0 per 100 000) and Indians (6.3 per 100
      000). Females had two times higher rates than males in all three races (age
      adjusted relative risk: 2.0, 95% CI: 1.7, 2.3). CONCLUSION: Malay and Indian
      people had identical rates of hospital admissions for PACG, which were only half
      the rates compared with Chinese.

PMID- 10966952
TI  - Use of sequential Heidelberg retina tomograph images to identify changes at the
      optic disc in ocular hypertensive patients at risk of developing glaucoma.
AB  - AIM: To determine if global and segmental changes in optic disc parameters of
      sequential Heidelberg retina tomograph (HRT) images develop in individual ocular
      hypertensive (OHT) patients without white on white visual field defects. METHODS:
      Patients and normal controls were recruited from a prospective ocular
      hypertension treatment trial. The subject groups consisted of 21 OHT patients who
      had converted to early glaucoma on the basis of visual field criteria (24-2
      program on the Humphrey perimeter), 164 OHT subjects with normal visual fields,
      and 21 normal controls. Sequential HRT images 16-21 months apart were obtained
      for each subject and segmental optic disc parameters were measured to determine
      if any change had occurred. From the analysis of sequential HRT images of the 21
      normal eyes we established normal limits of interimage variation. Individual
      discs in each group showing changes above the 95% limit of normal variability
      were then sought. RESULTS: Several segmental and global optic disc parameters
      were found to show significant change in the converter group before confirmed
      visual field change, confirming our previously published results. Individual
      optic disc analysis using the 95% limit of normal variability data demonstrated
      glaucomatous change in 13 out of 21 converter eyes. 47 of the 164 OHT eyes with
      normal visual fields showed change in global and segmental parameters in a
      "glaucomatous" direction above the level expected for normal variability. The
      parameters which changed most frequently in the OHT eyes were: global cup volume
      (6.7% of discs), inferonasal cup volume (11%), inferotemporal cup volume (8.5%),
      and superotemporal cup area (7.3%). CONCLUSIONS: We have identified change in a
      subset of ocular hypertensive patients which could predate the development of
      glaucomatous visual field loss. The HRT could be of value in the sequential
      follow up of those suspected of having glaucoma by identifying eyes at risk of
      developing glaucoma. However, further refinement of the technique is required to
      eliminate some of the inherent variability of the analysis method described, and
      to increase the ability to detect at risk individuals.

PMID- 10966953
TI  - Transscleral diode laser cyclophotocoagulation for the treatment of refractory
      glaucoma secondary to inflammatory eye diseases.
AB  - BACKGROUND: Inflammatory glaucoma is still a diagnostic and therapeutic dilemma
      and surgical intervention is always associated with a high risk of failure or
      reactivation of the inflammatory disease. In this study we prospectively examined
      the value of transscleral diode laser cyclophotocoagulation (TDLC) for the
      treatment of refractory inflammatory glaucoma. METHODS: 22 eyes of 20 consecutive
      patients with inflammatory, medically uncontrollable, glaucoma secondary to
      chronic uveitis/trabeculitis (n = 18), chemical injury (n = 2), episcleritis (n =
      1), and necrotising scleritis with inflammation (n = 1) were treated by TDLC.
      Nine eyes (41%) had had previous failed glaucoma surgery (trabeculectomy,
      cyclocryocoagulation) and 15 eyes (68.2%) had had previous anterior segment
      surgery. All patients were followed for 1 year after the initial treatment.
      RESULTS: Within 12 months of the first treatment the intraocular pressure was
      controlled in 77.3% of all eyes (72.2% of those with uveitic glaucoma). No
      serious side effects such as activation of the inflammatory process, phthisis
      bulbi or persistent hypotonia were observed, except one patient with a temporary
      fibrin reaction. More than one treatment was necessary in 63.6% of the patients.
      The use of systemic carbonic anhydrase inhibitors was reduced from 68.2% before
      treatment to 27.3% after 1 year. CONCLUSION: TDLC seems to be a safe and
      effective procedure for the treatment of inflammatory glaucoma and may become an
      alternative to trabeculectomy with antimetabolites in uveitic glaucoma. TDLC may
      become the surgical procedure of choice in treating secondary glaucoma caused by
      chemical injury and also in scleritis associated glaucoma, using reduced
      parameters for application.

PMID- 10966954
TI  - Topical ophthalmic beta blockers may cause release of histamine through cytotoxic
      effects on inflammatory cells.
AB  - AIM: To evaluate the effects of beta blockers used in ophthalmology on the
      release of histamine from mixed cell preparations containing human leucocytes and
      basophils. METHODS: A mixed leucocyte and basophil preparation was obtained from
      venous blood of healthy non-atopic volunteers. Cell preparations were then
      incubated with betaxolol, metipranolol, timolol, or carteolol. After incubation
      for 1 hour the histamine content of the supernatant was analysed by automated
      fluorometric analysis. Cell viability was tested by measuring lactate
      dehydrogenase (LDH) concentrations. RESULTS: Betaxolol and metipranolol in
      concentrations between 10(-2) M and 10(-3) M liberated histamine from human blood
      cells in a dose dependent manner. Carteolol and timolol had no effect on
      histamine at these concentrations. At the same concentrations LDH was also
      detected in the supernatants of cell suspensions incubated with metipranolol or
      betaxolol. CONCLUSIONS: Betaxolol and metipranolol induce substantial histamine
      release from human leucocytes, probably as a result of their cytotoxic effect.

PMID- 10966956
TI  - Effects of artefacts on scanning laser polarimetry of retinal nerve fibre layer
      thickness measurement.
AB  - AIMS: To investigate the effects of artefacts on scanning laser polarimetry of
      the retinal nerve fibre layer. METHODS: Six eyes of six normal volunteers and an
      artificial nerve fibre layer were examined using the nerve fibre analyser II. The
      retinal nerve fibre layer thickness (RNFLT) was measured in each of four 90
      degree quadrants, superior (S), temporal (T), inferior (I), and nasal (N), at 1.5
      disc diameters from the disc margin. Study 1: Measurement in normal eyes. The
      amount of maximum error in RNFLT measurements was investigated as follows: (1)
      the intensity setting of the laser beam was changed to be as weak as possible or
      to be as strong as possible; (2) the intentional offsets of the laser beam axis
      in relation to the pupil were made in four directions; (3) the eye was rotated by
      shifting the head 45 or 90 degrees; (4) the right eye was measured by moving it
      to the left eye position on the head rest. Study 2: Measurements on an artificial
      nerve fibre layer. The birefringence measurements were confirmed with a plastic
      disc, which has a radial arrangement of birefringence. The plastic disc with
      black paper was fixed at the right eye position or the left eye position on the
      head rest. The retardation of the laser beam by the plastic disc on the black
      paper was measured. The retardation of the plastic disc was checked by an
      automatic birefringence evaluation system (ABR-10A, Uniopt Co, Ltd, Shizuoka).
      RESULTS: Study 1: The effects of the rotated eye and the measurement of the
      opposite eye position were significant. The eyes rotated 90 degrees showed quite
      a different pattern in which the thicker and thinner locations of the RNFLT are
      switched. The nasal RNFLT of the baseline and the 90 degree rotated eye are 41.9
      (SD 6.0) microm and 122.5 (11.2) microm, respectively (p<0.0001, Scheffe multiple
      comparison test). Study 2: The uniform retardation of the plastic disc was
      observed with the ABR-10A. The NFA detects the retardation of the plastic disc
      which the retardation map showed as a double humped pattern. CONCLUSIONS: Study 2
      indicated that the amount of corneal compensation was not small. The cause of
      significant influences by the rotated eyes and right eyes measurement in left eye
      position were thought to be incorrect corneal compensation. To increase the
      diagnostic ability of SLP, an improved compensation of the cornea is thought to
      be important.

PMID- 10966955
TI  - Altitudinal visual field asymmetry is coupled with altered retinal circulation in
      patients with normal pressure glaucoma.
AB  - AIM: To compare the effect of altitudinal asymmetric glaucomatous damage on
      retinal microcirculation in patients with normal pressure glaucoma (NPG).
      METHODS: In a prospective cross sectional study patients with NPG (washed out for
      antiglaucomatous therapy) and altitudinal asymmetric perimetric findings between
      the superior and inferior hemisphere (Humphrey 24-2) (n=18) were included and
      compared with 20 NPG patients with symmetrical field defects and 18 healthy
      subjects. Fluorescein angiograms were performed using a scanning laser
      ophthalmoscope. Using digital image analysis, arteriovenous passage time (AVP)
      and vessel diameters were assessed for comparison of corresponding affected and
      less affected temporal arcades. RESULTS: Both affected and less affected
      hemispheres showed significantly prolonged AVP times (p<0.001) when compared with
      healthy subject data. In hemispheres with more severe glaucomatous field loss the
      AVP times were significantly (p=0.04) prolonged compared with the less affected
      hemisphere (AVP affected 3.1 (SD 7) seconds v AVP less affected 2.61 (1.4)
      seconds). There was no asymmetry effect on arterial and venous diameter
      measurements. CONCLUSION: Altitudinal visual field defects are linked together
      with circulatory deficits of the retinal tissue. The attenuated circulation seems
      to be a considerable factor in the natural course of glaucomatous optic
      neuropathy.

PMID- 10966957
TI  - The second eye of Japanese patients with unilateral exudative age related macular
      degeneration.
AB  - AIM: To clarify the incidence of choroidal neovascularisation (CNV) and
      predisposing findings for development of CNV in the second eye of Japanese
      patients with unilateral exudative age related macular degeneration (AMD).
      METHODS: The second eyes of unilaterally affected patients with exudative
      (neovascular) AMD treated in our clinic during the past 10 years (1988-97) were
      carefully followed up for more than a year. Evidence of CNV was confirmed by
      fluorescein and indocyanine green angiography. Macular lesions in patients, in
      whom CNV developed in the second eye, were retrospectively evaluated from patient
      records. RESULTS: 170 patients met the criteria. The average follow up period was
      47 months (range 12-108 months). All patients were Japanese. CNV developed in the
      second eye in 12 (7%) of 170 patients, 30.3 months on average after the first
      examination. Cumulative incidence of developing CNV in the second eye using
      Kaplan-Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3%
      by 5 years, and was relatively low compared with that in white patients. CNV
      developed most frequently from serous pigment epithelial detachment (PED) in the
      macula (58%). Soft drusen were not prevalent and risk of developing CNV was not
      very high (18%). CONCLUSION: It was confirmed that there were some differences in
      the incidence and predisposing findings for CNV developing in AMD among Japanese
      and other Asian patients compared with those in white people. It is important to
      recognise these differences between the two populations to understand the
      pathogenesis and epidemiology of AMD.

PMID- 10966958
TI  - Visual prognostic value of the pattern electroretinogram in chiasmal compression.
AB  - BACKGROUND/AIMS: The visual loss associated with compression of the optic chiasm
      by pituitary tumours may be transient or permanent, possibly related to the
      extent of irreversible retrograde degeneration to the retinal ganglion cells. The
      pattern electroretinogram (PERG) N95 component is thought to rise in relation to
      retinal ganglion cell function and hence may be a potential prognostic indicator
      for visual function following decompressive surgery. METHODS: The notes and
      electrodiagnostic records of 72 eyes from 36 patients with chiasmal compression
      were retrospectively analysed. RESULTS: The postoperative change in visual field
      was found to be associated with the PERG N95:P50 ratio (p=0.01). Improvement in
      visual field was shown by a greater proportion of eyes with a normal N95:P50
      ratio (65%) than with an abnormal ratio (27%). No change in visual field occurred
      in 26% of the eyes with a normal N95:P50 ratio compared with 67% of those with an
      abnormal ratio. Only 8% of eyes showed a worsening of visual field following
      surgery, in similar proportions for eyes with normal and abnormal N95:P50 ratios.
      There was no significant relationship with visual acuity. CONCLUSION: The PERG is
      a useful visual prognostic indicator in the preoperative assessment of chiasmal
      compression.

PMID- 10966959
TI  - Colour Doppler imaging of the orbital vasculature in Graves' disease with
      computed tomographic correlation.
AB  - AIMS: To evaluate alterations in orbital blood flow parameters and their
      correlations with extraocular muscle enlargement, proptosis, and intraocular
      pressure in patients with Graves' disease. METHODS: In this multicentre study
      blood flow parameters in the ophthalmic artery, superior ophthalmic vein, central
      retinal artery and vein were determined by colour Doppler imaging in 111 patients
      with Graves' disease in two groups (A and B) and 46 normal control subjects.
      Group A consisted of 42 patients with Graves' disease without ophthalmopathy;
      group B of 69 patients with Graves' disease with ophthalmopathy as detected by
      orbital computed tomographic scanning. RESULTS: Peak systolic and end diastolic
      velocities in the ophthalmic artery, peak systolic velocity in the central
      retinal artery, and maximal and minimal velocities in the central retinal vein in
      patients in group B were statistically significantly higher than those in group A
      and the normal controls, whereas maximal and minimal velocities in the superior
      ophthalmic vein in patients in group B were statistically significantly lower
      than those in group A and the control subjects. Peak systolic and end diastolic
      velocities in the ophthalmic artery, peak systolic velocity in the central
      retinal artery, and maximal and minimal velocities in the central retinal vein
      also correlated with the sum of all extraocular muscle diameters in group B (r >
      or =0.31, p< or =0.021). Blood flow parameters had no consistent correlation with
      proptosis or intraocular pressure (p>0.05). No statistically significant
      difference was found in resistivity indices between the groups (p>0.05). Reversed
      blood flow was noted in nine (13%) superior ophthalmic veins in group B.
      CONCLUSION: Orbital blood flow velocities are altered in patients with Graves'
      ophthalmopathy and may be detected by colour Doppler imaging. Some of these
      changes also correlate with the enlargement of extraocular muscles. The increased
      blood flow velocities in arteries may be secondary to orbital inflammation.

PMID- 10966960
TI  - Quality of life in myopia.
AB  - BACKGROUND: The safety and predictability of refractive surgery for all degrees
      of myopia is now becoming established. It is therefore appropriate to evaluate
      whether there is a patient driven demand for such treatments and, if so, to
      establish guidelines for its provision within the National Health Service (NHS).
      METHODS: A comparative study was designed to assess the effect of degree of
      myopia on quality of life ("high" (n = 30) -10.00D, worse eye; "moderate" (n =
      40) -4.00 to -9.75D, worse eye; "low" (n = 42) <-4. 00D, worse eye) compared with
      a group of patients with keratoconus (n = 30) treated by optical correction. Data
      collection included binocular logMAR visual acuity, Pelli-Robson low contrast
      letter sensitivity, questionnaires to assess subjective visual function (VF-14)
      and effect on quality of life (VQOL), and semi-structured interviews. RESULTS:
      There were no significant differences in any of the measures between patients
      with a high degree of myopia and those with keratoconus, or between those with a
      low and those with a moderate degree of myopia. However, those with a high degree
      of myopia had highly significantly poorer logMAR, VF-14, and VQOL scores than
      those with low and moderate myopia (p<0.001). Interview data supported these
      findings with patients with a high degree of myopia and those with keratoconus
      reporting that psychological, cosmetic, practical, and financial factors affected
      their quality of life. CONCLUSION: Compared with low and moderate myopia,
      patients with a high degree of myopia experience impaired quality of life similar
      to that of patients with keratoconus. Criteria should therefore be identified to
      enable those in sufficient need to obtain refractive surgical treatment under the
      NHS.

PMID- 10966961
TI  - Implementation methods for vision related quality of life questionnaires.
AB  - AIM: To determine the most reliable and consistent method and time interval over
      which to implement a vision impairment quality of life assessment tool. METHODS:
      117 patients with low vision aged 9-101 years were assigned into three age, sex,
      and visual function matched groups (n = 39 in each) to answer the Low Vision
      Quality of Life (LVQOL) questionnaire by post, telephone, or in person. The LVQOL
      questionnaire was completed on four occasions, each separated by four weeks.
      RESULTS: Postal implementation was the most cost effective method, showed the
      highest internal consistency of LVQOL items, but resulted in a lower apparent
      quality of life score than either telephone or in-person interviews (p<0.001).
      There was no difference in test-retest reliability between the three methods of
      implementation (p = 0.12). The profile of LVQOL scores showed a trend towards
      reduced quality of life scores 3 months after the baseline measures, although
      this was not significant. CONCLUSION: Posting may be the method of choice for
      clinical measurement of vision related quality of life. Patients with greater
      visual impairment were no less likely to complete a questionnaire when
      implemented by post and there was no apparent bias from other people assisting
      them. The quality of life measure can occur at any time up to 2 months after low
      vision rehabilitation for the progressive nature of conditions causing low vision
      not to cause a decreased baseline score. The LVQOL was shown to be a highly
      internally consistent and reliable method for measuring quality of life in the
      visually impaired.

PMID- 10966962
TI  - Pain perception with pH buffered peribulbar anaesthesia: a pilot study.
AB  - AIMS: To determine the relation between pH of anaesthetic solutions and patient
      perception of pain with peribulbar injection of local anaesthesia. METHODS: This
      prospective randomised controlled double blind pilot study involved 60
      consecutive patients who received a peribulbar block with either a standard
      acidic local anaesthetic of 5 ml 2% lignocaine and 5 ml of 0.5% bupivacaine
      (solution A), or an alkalinised solution composed of the same anaesthetic agents
      but with a pH of 7.44 (solution B). Before surgery patients were asked to grade
      the pain of both the preoperative dilating drops and the peribulbar injection
      using a visual analogue scale. RESULTS: The mean pain scores were similar in the
      two treatment groups-slightly higher (4.97) in group B who received the buffered
      solution, compared with group A (4.84) who received the plain solution. The small
      difference (-0.13, 95% confidence limits -1.6 and +1.3) was not significant.
      There was, however, a highly significant association between pain threshold
      ("drop pain") and injection pain levels (p<0.0001). CONCLUSION: This study showed
      no difference in the reduction in the pain experienced by patients undergoing
      peribulbar anaesthesia with pH buffered local anaesthetic. The study suggests the
      importance of "pain threshold" as a confounder and also showed the considerable
      pain felt by some patients on instillation of the preoperative dilating drops.

PMID- 10966963
TI  - Optic nerve oxygen tension: effects of intraocular pressure and dorzolamide.
AB  - AIM: To investigate the influence of acute changes in intraocular pressure on the
      oxygen tension in the vicinity of the optic nerve head under control conditions
      and after intravenous administration of 500 mg of the carbonic anhydrase
      inhibitor dorzolamide. METHODS: Domestic pigs were used as experimental animals.
      Oxygen tension was measured by means of a polarographic electrode in the vitreous
      0.5 mm anterior to the optic disc. This entity is called the optic nerve oxygen
      tension. Intraocular pressure was controlled by a hypodermic needle inserted into
      the anterior chamber and connected to a saline reservoir. RESULTS: When the
      intraocular pressure was clamped at 20 cm H2O optic nerve oxygen tension was 20
      (5) mm Hg (n=8). Intravenous administration of dorzolamide caused an increase in
      optic nerve oxygen tension of 43 (8)% (n=6). Both before and after administration
      of dorzolamide optic nerve oxygen tension was unaffected by changes in
      intraocular pressure, as long as this pressure remained below 60 cm H2O. At
      intraocular pressures of 60 cm H(2)O and below, dorzolamide significantly
      increased optic nerve oxygen tension. CONCLUSION: Intravenous administration of
      500 mg dorzolamide increases the oxygen tension at the optic nerve head during
      acute increases in intraocular pressure.

PMID- 10966964
TI  - Necrotising scleritis after bare sclera excision of pterygium.
AB  - AIM: To report cases of scleral necrosis after simple pterygium excision in which
      adjunctive treatment was not used. METHODS: We reviewed four patients who
      presented with scleral melt after pterygium excision without the use of
      adjunctive treatment in the form of beta irradiation, mitomycin C, or thiotepa.
      Each patient was thoroughly investigated to exclude underlying disease. RESULTS:
      Certain similarities were found between our patients with pterygium melt and
      cases of surgically induced necrotising scleritis including the location of melt,
      associated inflammation, and its response to steroid treatment in the latent
      period before they presented. CONCLUSION: Bare sclera pterygium excision can
      cause surgically induced necrotising scleritis years after the surgery.

PMID- 10966965
TI  - Real time fixation point monitoring system for photocoagulation of juxtafoveal
      neovascularisation.
AB  - BACKGROUND/AIMS: A new real time monitoring system has been developed to locate
      the fixation point during juxtafoveal laser photocoagulation. METHOD: The red
      diode laser beam is combined coaxially with the illumination beam to image a
      cross in the focal plane of the slit lamp, which allows projection of a red cross
      onto the patient's fundus. 27 patients with juxtafoveal choroidal
      neovascularisation were treated by photocoagulation using this system. RESULTS:
      13 (48%) patients whose visual acuity ranged from 20/200 to 20/40 answered that
      it was easier to keep the focus on the cross target image than on the aiming
      beam. The patient maintained stable fixation throughout the treatment. The laser
      treatment was completed without foveal damage near the fixation point in all
      patients. CONCLUSION: The real time fixation monitoring system should allow
      surgeons to treat juxtafoveal lesions with laser photocoagulation more safely and
      accurately.

PMID- 10966966
TI  - Anterior chamber flare after trabeculectomy and after phacoemulsification.
AB  - AIMS: To evaluate and compare prospectively the anterior chamber inflammatory
      response after phacoemulsification cataract surgery and after trabeculectomy with
      peripheral iridectomy. METHODS: Anterior chamber inflammation was measured using
      the Kowa FM-500 laser flare meter in 131 patients undergoing trabeculectomy and
      148 patients undergoing phacoemulsification cataract extraction with intraocular
      lens implantation. Flare was measured before surgery and on each postoperative
      visit up to 12 months. RESULTS: Before surgery there was no significant
      difference in flare readings between the two groups. Following trabeculectomy
      flare returned to baseline levels 4 weeks after surgery, while following
      phacoemulsification cataract extraction it remained significantly higher at week
      6 (p<0.006) and month 3 (p<0.05). CONCLUSIONS: Anterior chamber inflammation is
      more prolonged after cataract surgery than after trabeculectomy. This may have
      implications for the timing of trabeculectomy in relation to cataract surgery.

PMID- 10966967
TI  - Prevalence of retinopathy at diagnosis among type 2 diabetic patients attending a
      diabetic centre in South India.
AB  - AIM: To assess the prevalence of retinopathy in newly diagnosed south Indian type
      2 diabetic patients attending a diabetic centre. METHODS: 448 consecutive newly
      diagnosed type 2 diabetic patients were recruited. Four field retinal colour
      photography was performed and graded using a modified form of the Early Treatment
      Diabetic Retinopathy Study grading system. RESULTS: Of the 438 patients with
      assessable photographs, 32 (7.3%, 95% confidence interval 5.0 to 10. 2) had
      retinopathy. None of the variables tested showed a significant association with
      retinopathy on univariate or multivariate logistic regression analysis.
      CONCLUSION: The overall prevalence of retinopathy at diagnosis among clinic based
      south Indian patients with type 2 diabetes appears to be lower than that reported
      among Europeans.

PMID- 10966969
TI  - Intravitreal injection of crystalline cortisone as adjunctive treatment of
      proliferative vitreoretinopathy.
AB  - AIM: To report on clinical outcome and complications of intravitreal injection of
      crystalline cortisone in patients undergoing pars plana vitrectomy for treatment
      of proliferative vitreoretinopathy. METHODS: The study included all 16 patients
      who underwent pars plana vitrectomy for treatment of proliferative
      vitreoretinopathy, who received an intravitreal injection of 10-20 mg crystalline
      triamcinolone acetonide at the end of surgery, and who were operated on by the
      same surgeon. Most of the vehicle of the solution containing the cortisone
      crystals was removed before performing the injection. Mean follow up time was
      1.64 (SD 2.15) months (median 1. 23 months; range 0.20-9.20 months). The study
      group was compared with a control group which consisted of 144 patients
      undergoing pars plana vitrectomy for proliferative vitreoretinopathy performed by
      the same surgeon. RESULTS: In the study group compared with the control group,
      intraocular inflammation, as estimated clinically by slit lamp biomicroscopy, was
      lower, appearance of the fundus upon ophthalmoscopy in the first postoperative
      week was clearer, and postoperative pain in the first two postoperative days was
      reduced. Intraocular pressure measured at the end of the first postoperative week
      did not vary significantly between the groups. A pseudohypopyon consisting of
      cortisone crystals in the inferior anterior chamber angle was detected in one
      patient. Postoperative infectious endophthalmitis was not encountered.
      CONCLUSIONS: This pilot study suggests that intravitreal injection of crystalline
      cortisone with most of the vehicle removed is not toxic to intraocular
      structures, reduces postoperative intraocular inflammation, and may be a
      potentially useful additional tool in the treatment of proliferative
      vitreoretinopathy.

PMID- 10966968
TI  - Subretinal fluid levels of topical, oral, and combined administered ciprofloxacin
      in humans.
AB  - AIMS: To investigate the subretinal fluid (SRF) penetration of ciprofloxacin
      following topical, oral, and combined administration. METHODS: 34 patients
      undergoing conventional retinal reattachment surgery were randomly assigned to
      three groups. Twelve patients received topical ciprofloxacin, 11 patients
      received oral ciprofloxacin, and the other 11 patients received combined drug
      administration. SRF drug level was measured by using high performance liquid
      chromatography method. RESULTS: The highest drug concentrations of all tested
      modes were attained following combined administration and lowest following
      topical administration (p<0.001). The SRF drug concentration following oral
      administration was also significantly higher than that of topical administration
      (p<0.001). Concentrations after oral and combined administration did not differ
      significantly (p = 0.217). CONCLUSIONS: Topical ciprofloxacin can penetrate SRF.
      Ocular bioavailability of ciprofloxacin in SRF after oral and combined
      administration is equivalent.

PMID- 10966970
TI  - Tumour location affects the incidence of cataract and retinopathy after
      ophthalmic plaque radiation therapy.
AB  - AIM: To examine how tumour location affects ocular morbidity after ophthalmic
      plaque radiotherapy for uveal melanoma. METHODS: 69 eyes were irradiated and
      followed for a mean 42 months. There were 23 anterior uveal melanomas and 46 were
      posterior to the equator. Anterior and posterior tumours had similar basal
      dimensions. Their mean apical heights were 4.8 mm (anterior) and 3.5 mm
      (posterior) which received a mean 88 Gy and 83.4 Gy respectively. RESULTS: Only
      one patient (4%) plaqued for an anterior uveal melanoma developed secondary
      retinopathy (cystoid macular oedema). In contrast, 24 (52%) of the posterior
      choroidal melanoma patients developed retinopathy (p value <0.0001). Cataract
      developed in 18 (86%) eyes with phakic anterior tumour compared with seven (17%)
      eyes with posterior tumours (p value <0.0000). No posterior nasal tumours lost
      more than two lines of vision though 45% developed retinopathy. CONCLUSION: While
      plaque radiation of anterior melanomas is more likely to cause reversible vision
      loss secondary to cataract, treatment of posterior tumours is more likely to be
      associated with irreversible loss because of retinopathy. Nasal location is also
      protective against severe loss of vision.

PMID- 10966972
TI  - Age related macular disease.

PMID- 10966971
TI  - Does extraocular muscle proprioception influence oculomotor control?

PMID- 10966973
TI  - Randomised controlled trial of corticosteroid regimens in endothelial corneal
      allograft rejection.

PMID- 10966974
TI  - Indocyanine green guided laser photocoagulation in patients with occult choroidal
      neovascularisation.

PMID- 10966975
TI  - Phacoemulsification combined with silicone oil removal through posterior
      capsulorhexis.

PMID- 10966976
TI  - Susceptibility to ocular autoimmune disease.

PMID- 10966977
TI  - Sex selection and preimplantation diagnosis: a response to the Ethics Committee
      of the American Society of Reproductive Medicine.
AB  - In its recent statement 'Sex Selection and Preimplantation Genetic Diagnosis',
      the Ethics Committee of the American Society of Reproductive Medicine concluded
      that preimplantation genetic diagnosis for sex selection for non-medical reasons
      should be discouraged because it poses a risk of unwarranted gender bias, social
      harm, and results in the diversion of medical resources from genuine medical
      need. We critically examine the arguments presented against sex selection using
      preimplantation genetic diagnosis. We argue that sex selection should be
      available, at least within privately funded health care.

PMID- 10966978
TI  - Embryo implantation and GnRH antagonists: GnRH antagonists in ART: lower embryo
      implantation?
AB  - Recently, concerns have been raised regarding possible adverse effects of
      gonadotrophin-releasing hormone (GnRH) antagonists on extra-pituitary
      reproductive cells and organs, i.e. ovarian cells, oocyte, embryo, endometrium.
      These concerns are based on numerous in-vitro studies suggesting decreased
      biosynthesis of growth factors caused by local action of GnRH antagonists.
      Clinically, it has been shown that the use of high doses (< or =1 mg daily) of
      GnRH antagonists is associated with low implantation rates in IVF. Although such
      direct adverse effect of GnRH antagonists cannot be ruled out at this time, so
      far clinical experience points to profound LH suppression as the major caveat
      associated with the use of high doses of GnRH antagonists. Very low LH
      concentrations are associated with aberrant concentrations of oestradiol during
      ovarian stimulation, which may in turn adversely effect implantation potential.
      The clinical data available thus far on the use of GnRH antagonists originate
      from protocols designed for clinical studies. It is predicted that as more
      clinical experience is gained, and with protocol modifications to suit individual
      patient response, GnRH antagonists will be comparable with the agonists in terms
      of cycle outcome.

PMID- 10966979
TI  - Embryo implantation and GnRH antagonists: GnRH antagonists do not activate the
      GnRH receptor.
AB  - Recent suggestions that gonadotrophin-releasing hormone (GnRH) antagonists
      activate the GnRH receptor are discussed. Most of the studies cited in support of
      this suggestion are in-vitro studies, testing supra-pharmacological doses of GnRH
      analogues in cancer cell lines, whereas GnRH antagonists, e.g. ganirelix or
      cetrorelix, do not affect the steroidogenesis of human granulosa cells in vitro.
      In patients treated with GnRH antagonists prior to IVF or intracytoplasmic sperm
      injection (ICSI), oocyte maturity and fertilization rates are equal to those
      achieved following a long protocol of GnRH agonists. Although there is a tendency
      towards a lower pregnancy rate (not statistically significant) in the initial
      trials using GnRH antagonist with either recombinant FSH or human menopausal
      gonadotrophin (HMG) for ovarian stimulation, this new treatment option of GnRH
      antagonists facilitates short and simple treatment and improves the convenience
      and safety for the patient. As with GnRH agonists in the past, the clinical
      outcome of GnRH antagonist treatment will improve with time as more clinical
      experience is gained (learning curve) and the treatment protocol is optimized.
      Moreover, a GnRH agonist instead of human chorionic gonadotrophin (HCG) may be
      used for triggering ovulation and will decrease the cancellation rate and
      minimize the risk for developing ovarian hyperstimulation syndrome (OHSS).

PMID- 10966980
TI  - Avoiding multiple pregnancies in ART: a plea for single embryo transfer.
AB  - It has been generally accepted that triplets after IVF/intracytoplasmic sperm
      injection (ICSI) can and should be avoided by adopting a standard strategy of
      replacing no more than two embryos. However, there is an increasing awareness of
      the risks and costs and of the epidemic size of twin pregnancies after IVF/ICSI.
      This has resulted in efforts to replace no more than one embryo. However, this
      approach has been hampered by our relative inability to identify embryos with a
      very high implantation potential. To identify such embryos, a number of
      strategies are being considered, both at the two pronuclear (2PN), early cleavage
      and the blastocyst stages. At the 2PN stage, the polarity characteristics of the
      nucleoli have been shown to be correlated with a high implantation rate.
      Similarly, the morphological characteristics at day 2 and 3 have been used to
      describe top quality embryos in approximately 75% of all IVF/ICSI cycles.
      Blastocyst culture has resulted in very high implantation rates in the hands of
      some authors. No approach has shown its superiority at present, but initial
      experience with single embryo transfer (SET) at the early cleavage stage by
      Scandinavian and Belgian groups shows that an ongoing pregnancy rate of 35% and
      more can be achieved. Proper identification of patients at risk of a twin
      pregnancy after double embryo transfer is equally important. It is clear that
      mainly young patients (aged <34 years) during their first, perhaps first two,
      IVF/ICSI cycles constitute the main population at risk (responsible for >80% of
      all twins) and are the main target group for twin prevention by SET of a top
      quality embryo at whatever stage. Therefore, in our opinion, although a further
      fine-tuning of both embryo and patient characteristics relating to a high risk
      for (twin) pregnancy is desirable, SET should be introduced carefully and
      progressively in each IVF/ICSI programme from now on. Correct counselling is very
      important and both public and private insurers will have to join in the
      discussion.

PMID- 10966981
TI  - Immunolocalization of Fas and Fas ligand in the ovaries of women with polycystic
      ovary syndrome: relationship to apoptosis.
AB  - Both Fas (APO-1, CD95), an apoptosis-inducing receptor, and its ligand, Fas
      ligand (FasL, CD95L), have been localized to the ovary. Granulosa cell apoptosis
      occurs in antral follicular atresia. In polycystic ovary syndrome (PCOS), antral
      follicles accumulate with some atretic features. The ovarian expression of Fas
      and FasL was examined in PCOS by immunohistochemistry and correlated with
      immunodetection of apoptotic cells. Fas immunostaining was present in pre-antral
      follicle oocytes, some primary and secondary pre-antral follicle granulosa cells,
      and both granulosa and theca of antral follicles. Thecal staining persisted with
      advancing atresia, while granulosa staining declined. In antral follicles,
      abundant Fas-positive cells co-localized with scattered nuclei immunopositive for
      apoptosis. Ovarian vascular myocytes were strongly Fas-immunopositive. FasL
      immunostaining was present in pre-antral follicles in oocytes and variably in
      granulosa. In antral follicles, granulosa and thecal FasL staining increased with
      advancing atresia. Normal control ovaries showed follicular Fas and FasL staining
      patterns similar to those in PCOS, but vascular staining was less prominent. In
      one healthy follicle, Fas immunostaining was seen in the oocyte and weakly in
      mural granulosa and theca interna. The results suggest that in PCOS, an
      alteration in Fas-mediated apoptosis, does not cause abnormal folliculogenesis,
      but may promote ovarian vascular remodelling.

PMID- 10966983
TI  - A rapid decline in serum oestradiol concentrations around the mid-luteal phase
      had no adverse effect on outcome in 763 assisted reproduction cycles.
AB  - Progesterone is essential in the luteal phase whereas luteal oestradiol may play
      only a permissive role on the endometrium. However, a rapid decline in oestradiol
      concentrations around the mid-luteal period may compromise the endometrial
      integrity leading to poor IVF outcomes. A retrospective analysis of 763 women
      aged <40 years undergoing their first IVF cycle and having < or =3 embryos
      replaced was undertaken. In cycles receiving human chorionic gonadotrophin (HCG)
      for luteal support, 25th, 50th and 75th centiles of the ratio of day-of-HCG
      oestradiol to mid-luteal oestradiol (oestradiol ratio) were 1.8, 2.8 and 5.0
      respectively. Hormonal parameters were not different between pregnant and non
      pregnant cycles. The outcomes were similar irrespective of the oestradiol ratio.
      Progesterone supplementation was used instead when the HCG oestradiol was >18 000
      pmol/l or there were features of ovarian hyperstimulation syndrome. Pregnancy
      rates of these hyperstimulated cycles were 16.7 and 11.4% per cycle respectively
      when oestradiol ratio was < or =5.0 and >5.0. This difference did not reach
      statistical significance. Our results could not find an adverse outcome in cycles
      showing a rapid decline in oestradiol during the mid-luteal phase.

PMID- 10966982
TI  - A biological, immunological and physico-chemical comparison of the current
      clinical batches of the recombinant FSH preparations Gonal-F and Puregon.
AB  - The immunopotency and in-vitro biopotency of clinical batches of Gonal-F((R)) and
      Puregon((R)) (recombinant human follicle stimulating hormones) were compared and
      their carbohydrate chains investigated for charge heterogeneity and internal
      carbohydrate complexity. Immunopotency (IU/pmol) for both Gonal-F and Puregon was
      0.35 +/- 0.01 and biopotency (ED(50), pmol/l) was similar, being 7.3 +/- 0.6 and
      5.4 +/- 0.2 respectively. Charge distributions were essentially the same with no
      difference either in median isoelectric point (pI) (between 4.26 and 4.50), or in
      the bulk of material fractionated between pI 4 and 5 (66.0 +/- 1.8% Gonal-F and
      72.0 +/- 1.8% Puregon). However, there were minor differences in charge at
      extremes of pI, Gonal-F being slightly more acidic: 18.2% Gonal-F versus 9.8%
      Puregon at pI 3.5-4.0 (P: = 0.03) and 6.7% Gonal-F versus 10.7% Puregon at pI 5.0
      5.5 (P: = 0.03). Carbohydrate complexity was the same: 9.3 versus 10.9 (complex),
      76.6 versus 78.6 (intermediate) and 14.1 versus 10.5% (simple). In summary, Gonal
      F and Puregon have similar immunopotency, in-vitro biopotency and internal
      carbohydrate complexity, differing slightly in charge heterogeneity, Gonal-F
      having more acidic glycoforms. We conclude them to be intrinsically very similar,
      expecting no difference in clinical efficacy on the basis of respective
      structure.

PMID- 10966984
TI  - Expected contribution to serum oestradiol from individual ovarian follicles in
      unstimulated cycles.
AB  - Data relating serum oestradiol concentration to follicle size in unstimulated
      cycles are lacking. We provide precise data on serum concentrations expected for
      any follicle diameter (FD) in the mid- to late follicular phase. Infertile women
      (n = 35) with apparently normal ovulatory cycles were studied in detail in 128
      unstimulated monofollicular cycles leading to IVF. Using mathematical modelling
      to account for repeated cycles in the same woman, the relationship between serum
      oestradiol and FD was explored and reference ranges for serum oestradiol at
      individual FD were calculated. Serum oestradiol concentrations [number of
      patients, geometric mean, 95% confidence interval (CI)] at the onset of the LH
      surge were higher in 'fertilized' cycles (73, 1279, 1180-1378 pmol/l) compared
      with 'unfertilized' cycles (31, 1055, 929-1197 pmol/l, P: = 0.008) and 'no
      oocyte' cycles (24, 1064, 922-1227 pmol/l, P: = 0.03) respectively. In
      'fertilized' cycles, oestradiol concentrations rose exponentially with FD and for
      each size of follicle the oestradiol distribution was skewed. Functional oocyte
      competence varied in apparently normal ovulatory cycles and was correlated with
      pre-ovulatory serum oestradiol but not FD. Serum oestradiol varies within wide
      limits for maturing follicles of any given diameter prior to the onset of the LH
      surge.

PMID- 10966985
TI  - Cortical vein thrombosis misinterpreted as intracranial haemorrhage in severe
      ovarian hyperstimulation syndrome: case report.
AB  - A case of cortical vein thrombosis presenting as intracranial haemorrhage is
      described in a patient with ovarian hyperstimulation syndrome (OHSS) after IVF
      and embryo transfer. Veno-occlusive disease of the brain could appear as a
      haemorrhagic lesion on magnetic resonance imaging (MRI) and this made the initial
      diagnosis of cortical vein thrombosis difficult. The patient developed deep vein
      thrombosis 2 weeks after the intracranial event and the diagnosis of cortical
      vein thrombosis was made at that time on MRI study after the resolution of the
      haemorrhage. This patient actually developed generalized thrombosis as a
      complication to OHSS. Although the initial MRI picture may be misleading, the
      diagnosis of thrombosis should always be kept in mind, as it is the commonest
      cause of intracranial lesions after OHSS.

PMID- 10966986
TI  - Apoptosis of testicular germ cells induced by exogenous glucocorticoid in rats.
AB  - The influence of exogenous glucocorticoid, dexamethasone (Dex), on testicular
      germ cell apoptosis was investigated in rats. The percentages of apoptotic
      tubules and apoptotic germ cells in the Dex-treated group of rats were about
      seven-fold and 10-fold higher respectively than in either the control group, or
      in rats treated with glucocorticoid receptor agonist (GR-A), or in rats treated
      with both Dex and GR-A. These results suggest that, in rats, apoptosis of
      testicular germ cells is mediated by glucocorticoid receptors.

PMID- 10966987
TI  - Right-sided ovulation favours pregnancy more than left-sided ovulation.
AB  - The aim of this study was to evaluate whether frequency of ovulation and
      fertility potential of oocytes from the two ovaries differed in regularly
      menstruating women (1057 cycles of 856 fertile women and 1033 cycles of 258
      infertile women). For both fertile and infertile women ovulation from the right
      ovary occurred more often than from the left ovary (55 versus 45%; P: < 0.005).
      In infertile women follicular phase length was similar for right- and left-sided
      ovulation. However, infertile women treated with intrauterine insemination (IUI)
      or in-vitro fertilization (IVF) showed a pregnancy rate in connection with right
      sided ovulation (13%) which was higher than that of left-sided (9%). The ratio of
      pregnancies deriving from the right ovary per total number of pregnancies was
      similar in infertile and fertile women (64.6%, 73/113 and 63.4%, 361/569
      respectively). The ratio of pregnancies from right-sided ovulation (approximately
      64%) per total number of pregnancies was higher than that of right-sided
      ovulation (approximately 55%) during non-pregnant cycles (P: < 0.0001). The
      implantation rate in right-sided ovulation seemed to be higher than in left-sided
      one, since IVF data showed a lower frequency (P: = 0.03) of pre-embryo formation
      from right-sided ovulation than left-sided. Mid-luteal serum oestradiol and
      testosterone were higher (P: < 0.05) in right-sided ovulation than left-sided.
      Taken together, in both fertile and infertile women the fertility potential of
      oocytes from the right ovary surpasses that of the left ovary.

PMID- 10966988
TI  - Source of calcium for contractile responses of large and small human
      intramyometrial arteries.
AB  - The role of calcium (Ca(2+)) released from intracellular stores and the entry of
      extracellular Ca(2+) for vasopressin (AVP)-induced responses in large and small,
      human, intramyometrial arteries was investigated. There was no statistical
      difference as revealed by pD(2) values (-log EC(50)), in the sensitivity of large
      and small vessels to AVP. Nimodipine caused an inhibition of contractions induced
      by low concentrations (10(-10) mol/l) of AVP in both types of vessels but, at
      higher concentration (>10(-10) mol/l), whereas responses in small arteries were
      diminished, in large arteries they remained unchanged. In Ca(2+)-free solution,
      responses of large and small arteries to potassium and to 10(-10) mol/l AVP were
      abolished. With 10(-6) mol/l AVP, response in small arteries was completely
      inhibited, whereas in large arteries it was reduced by approximately 50%.
      Additional experiments were done on large arteries. Thapsigargin (TSG), which
      causes depletion of internal Ca(2+) stores, caused a significant reduction in
      responses. Following treatment with TSG, responses to AVP in Ca(2+)-free solution
      were almost completely inhibited but arteries responded again when incubated in
      normal physiological salt solution. The results indicate that in contrast to
      large arteries, small arteries are highly dependent on extracellular Ca(2+).
      Response of large arteries showed considerable dependence on Ca(2+) stored
      internally particularly, for maximum activation.

PMID- 10966989
TI  - Antibodies to phosphatidylethanolamine and phosphatidylserine are associated with
      increased natural killer cell activity in non-male factor infertility patients.
AB  - Antiphospholipid antibodies (APA) have been identified in patients with recurrent
      pregnancy loss and IVF failure. Of these, antiphosphatidylethanolamine (aPE) and
      antiphosphatidylserine (aPS) may have special significance. A link between
      increased natural killer cell activity (NKa+) and trophoblast cell apoptosis has
      also been reported. This study was undertaken to determine how the APA profile
      was associated with peripheral NK cell activity. We evaluated 197 female IVF
      candidates for APA and NKa. Eighty-nine patients (45%) were APA+ and of these, 51
      (57%) were aPE/aPS+. Fifty-four patients (27%) had increased NK cell activity.
      Some 51% of APA+ and 78% of aPE/aPS+ patients had increased NK cell activity
      compared with 8% and 13% when APA and aPE/aPS tested negative respectively (P: <
      0.0001). Non-male factor infertility patients were APA+ and NKa+ in 57% and 34%
      of cases respectively, compared with 19% and 13% if a pure male factor was
      present. Some 88% of aPE/aPS+, non-male factor patients had increased NK cell
      activity, compared with 12% who tested aPE/aPS negative (P: < 0.0001) and 25% of
      aPE/aPS+, isolated male factor patients (P: < 0.0001). These findings establish a
      direct relationship between APA (specifically aPE/aPS) and increased peripheral
      NK cell activity among non-male factor infertility patients. It is possible that
      APA do not directly cause reproductive failure but rather function as markers or
      intermediaries for an underlying, abnormal activation of cellular immunity.

PMID- 10966990
TI  - The significance of the number of antral follicles prior to stimulation in
      predicting ovarian responses in an IVF programme.
AB  - Multiple follicular development plays a major role in the successful outcome of
      IVF and embryo transfer treatment. Prediction of ovarian responses prior to
      stimulation is useful in counselling patients and helpful in tailoring the dosage
      of gonadotrophin to individual patients. The objective of this study was to
      compare age of women, body mass index (BMI), basal FSH concentration, volume of
      both ovaries and the number of antral follicles of both ovaries in predicting the
      number of oocytes obtained. A total of 128 consecutive women, who had no history
      of ovarian surgery, were non-smokers and undergoing the first cycle using a
      standard regimen of ovarian stimulation were examined. The total number of antral
      follicles achieved the best predictive value, followed by basal FSH, BMI and age
      of women. In those women with fewer antral follicles, a longer duration and
      higher dosage of human menopausal gonadotrophin were required but the number of
      eggs obtained was significantly less than for those with more antral follicles.
      Significantly more cycles were cancelled before egg collection in women with < or
      =6 antral follicles while more cycles of embryo transfer were postponed in order
      to reduce the risk of ovarian hyperstimulation syndrome in women with >9 antral
      follicles.

PMID- 10966991
TI  - Influence of position and length of uterus on implantation and clinical pregnancy
      rates in IVF and embryo transfer treatment cycles.
AB  - In a prospective study of 807 consecutive women shown to have an apparently
      normal uterus after hysterosalpingography, hysteroscopy or pelvic ultrasonography
      prior to IVF or intracytoplasmic sperm injection (ICSI) and embryo transfer, the
      position and length of the uterine cavity was measured routinely at a pre
      treatment mock transfer procedure. The apparent length of the uterine cavity was
      <7 cm in 128 women (group 1), 7-9 cm in 594 women (group 2) and >9 cm in 85 women
      (group 3). The uterus was noted to be retroverted in 38. 2% (308) women. The
      embryo transfer catheter was advanced to 5 mm from the uterine fundus based on
      the previously determined cavity length in all the embryo transfer procedures at
      48 h after oocyte collection. Implantation and clinical pregnancy rates were not
      significantly different with respect to position of the uterus, difficulties
      encountered in passage of the catheter, mean age of the women, aetiology or
      duration of infertility or embryology events. An apparently greater cavity length
      was seen in older and/or parous women, but the difference was not statistically
      significant. Although the highest implantation and clinical pregnancy rates were
      seen in women with a cavity length of 7-9 cm (group 2) the differences were not
      statistically significant: group 1, 18.9 and 36. 7%; group 2, 21.0 and 46.5%; and
      group 3, 17.3 and 32.9% respectively. The incidence of ectopic pregnancy per
      reported clinical pregnancy was highest in group 1 women, being 14.9% (7/47) in
      comparison with group 2 (1.8%, 5/276) and group 3 (0%, 0/27) (P: < 0.0005),
      suggesting that the size of the uterus is a critical factor in the aetiology of
      ectopic pregnancy in IVF/ICSI-embryo transfer.

PMID- 10966992
TI  - Day 5 versus day 3 embryo transfer: a controlled randomized trial.
AB  - Blastocyst transfer has been suggested to improve implantation rate without
      affecting pregnancy rate. The aim of this study was to compare the pregnancy and
      implantation rates of day 3 and 5 transfers in a prospective randomized manner.
      Patients with four or more zygotes were randomly allocated on day 1 to either day
      3 or 5 transfers. Fertilization was achieved through regular IVF or
      intracytoplasmic sperm injection. Zygotes were kept in Medicult IVF medium for
      day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively
      for day 5 transfers. The morphologically best two or three embryos or blastocysts
      were chosen for transfer in both groups. Overall pregnancy rates per embryo
      transfer were the same (39%) in day 3 and 5 transfers. Implantation rates were 21
      and 24% for day 3 and 5 transfers respectively. The pregnancy and implantation
      rates for day 5 transfers were significantly affected by the availability of at
      least one blastocyst to transfer and the number of zygotes. The number of good
      quality embryos on day 3 also significantly affected pregnancy and implantation
      rates on day 5 transfers. Multiple gestation rate, number of abortions and
      ongoing pregnancies were similar in both groups. In conclusion, day 3 and 5
      transfer had similar pregnancy, implantation and twinning rates. Currently, day 5
      transfers have no advantages over day 3 transfers.

PMID- 10966993
TI  - The prognostic power of the post-coital test for natural conception depends on
      duration of infertility.
AB  - Controversy about the value of the post-coital test (PCT) has prompted us to re
      analyse data from 207 couples, originally studied between 1982 and 1983, with at
      least 12 months' infertility at presentation, complete diagnostic information and
      exclusion of female factors, to clarify the effect of duration of infertility on
      the prediction of conception. In couples with less than 3 years infertility and a
      positive PCT, 68% conceived within 2 years compared with 17% of those with a
      negative result. After 3 years, corresponding rates were 14% and 11%. The
      relative risks of conception [95% confidence interval (CI)] calculated using the
      Cox's proportional hazards model were 0.23 (0.12-0.43) for a negative PCT
      (reference positive PCT) and 0.25 (0.13-0.51) for more than 36 months infertility
      (reference 12-23 months). Semen analysis had no extra predictive power given the
      duration of infertility and the PCT. The PCT is an effective predictor of
      conception where defined female causes of infertility are absent and duration of
      infertility is less than 3 years. Once infertility is prolonged (beyond 3 years)
      the conception rate is low even with a positive test because a large proportion
      of couples remaining childless so long have true unexplained infertility. Use of
      the PCT will enable clinicians to allocate scarce, expensive and invasive
      resources effectively.

PMID- 10966994
TI  - Fertility and offspring sex ratio of men who develop testicular cancer: a record
      linkage study.
AB  - Analysis of associations between testicular cancer, subfertility and offspring
      sex ratio (proportion of males born among newborns) was performed on 3530 Danish
      men, born 1945-1980, who developed testicular cancer in the period 1960-1993. As
      the basis of comparison we used the total population of Danish men born in the
      period 1945-1980 (n = 1 488 957) and their biological children (n = 1 250 989).
      Men who developed testicular cancer had, prior to the cancer diagnosis, a reduced
      fertility (standardized fertility rate ratio: 0.93, 95% confidence interval: 0.89
      0.97) and a significantly lower proportion of boys (48.9%, P: = 0.02) compared
      with the general population (51.3%). The reduction in fertility was more
      pronounced in men with non-seminoma but the reduction in offspring sex ratio was
      independent of histological type. This confirms earlier results from less
      conclusive studies and indicates that testicular cancer, male subfertility and a
      female-biased sex ratio among new-born infants are characteristics of male
      reproduction that are linked by biological mechanisms.

PMID- 10966995
TI  - Triploid pregnancy after ICSI of frozen testicular spermatozoa into cryopreserved
      human oocytes: case report.
AB  - Although freezing oocytes is ethically more acceptable than cryopreservation of
      embryos, variable oocyte survival, fertilization rate and possible risk of
      increased ploidy after cryopreservation have precluded the widespread clinical
      application of oocyte cryopreservation in assisted reproduction techniques. We
      report a triploid pregnancy from intracytoplasmic sperm injection of recombinant
      FSH-stimulated frozen/thawed testicular spermatozoa into cryopreserved oocytes in
      a hormone replacement cycle. To our knowledge, this is the first report of a
      pregnancy where both gametes have been frozen. It illustrates the need for
      further research when applying new techniques in assisted reproduction.

PMID- 10966996
TI  - Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH
      antagonist ganirelix treatment in women undergoing ovarian stimulation for
      assisted reproduction, with special reference to the prevention of ovarian
      hyperstimulation syndrome: preliminary report: short communication.
AB  - A new treatment option for patients undergoing ovarian stimulation is the
      gonadotrophin-releasing hormone (GnRH) antagonist protocol, with the possibility
      to trigger a mid-cycle LH surge using a single bolus of GnRH agonist, reducing
      the risk of developing ovarian hyperstimulation syndrome (OHSS) in high
      responders and the chance of cycle cancellation. This report describes the use of
      0.2 mg triptorelin (Decapeptyl) to trigger ovulation in eight patients who
      underwent controlled ovarian hyperstimulation with recombinant FSH (rFSH,
      Puregon) and concomitant treatment with the GnRH antagonist ganirelix
      (Orgalutran) for the prevention of premature LH surges. All patients were
      considered to have an increased risk for developing OHSS (at least 20 follicles >
      or =11 mm and/or serum oestradiol at least 3000 pg/ml). On the day of triggering
      the LH surge, the mean number of follicles > or =11 mm was 25.1 +/- 4.5 and the
      median serum oestradiol concentration was 3675 (range 2980-7670) pg/ml. After
      GnRH agonist injection, endogenous serum LH and FSH surges were observed with
      median peak values of 219 and 19 IU/l respectively, measured 4 h after injection.
      The mean number of oocytes obtained was 23.4 +/- 15.4, of which 83% were mature
      (metaphase II). None of the patients developed any signs or symptoms of OHSS. So
      far, four clinical pregnancies have been achieved from the embryos obtained
      during these cycles, including the first birth following this approach. It is
      concluded that GnRH agonist effectively triggers an endogenous LH surge for final
      oocyte maturation after ganirelix treatment in stimulated cycles. Our preliminary
      results suggest that this regimen may prove effective in triggering ovulation and
      could be said to prevent OHSS in high responders. The efficacy and safety of such
      new treatment regimen needs to be established in comparative randomized studies.

PMID- 10966998
TI  - Relationship between classic histological pattern and sperm findings on fine
      needle aspiration map in infertile men.
AB  - Systematic testis fine needle aspiration (FNA) mapping has been proposed as an
      adjunctive or alternative diagnostic procedure to biopsy to determine the
      presence of spermatozoa within infertile testes. This study related testis
      histology to the global presence or absence of spermatozoa in the same testes
      determined by FNA cytology. Testis biopsies and FNA mapping were performed in 87
      infertile, azoospermic men. A mean of 1.3 biopsies and 14 FNA sites were taken
      per patient. Biopsies were assessed by recognized histological patterns of
      normal, Sertoli cell-only, hypospermatogenesis, early and late maturation arrest,
      sclerosis as well as mixed patterns that included at least two of these
      histologies. FNA cytological specimens were assessed for sperm presence by an
      experienced cytologist. Overall, spermatozoa were found by FNA mapping in 52% of
      patients. A comparison of histology and FNA findings revealed that pure patterns
      of Sertoli cell-only and early maturation were associated with a very poor
      likelihood of sperm detection (4-8%). In contrast, patients with other pure
      pattern histologies or mixed patterns had high rates of FNA sperm detection (77
      100%). Similar to reported testicular sperm extraction (TESE) findings, sperm
      detection with FNA shows wide variation depending on testis histology. Unlike
      most TESE reports, however, some histological patterns generally reflect a more
      global testicular dysfunction and poorer likelihood of sperm identification,
      suggesting the possibility that these phenotypes have a genetic origin.
      Systematic testis sampling with FNA offers additional geographical information
      about spermatogenesis that routine biopsies lack and can further guide couple
      decision-making in severe male factor infertility.

PMID- 10966997
TI  - Once a month administration of mifepristone improves bleeding patterns in women
      using subdermal contraceptive implants releasing levonorgestrel.
AB  - It has been suggested that the administration of an anti-progesterone might
      improve bleeding patterns in women with irregular bleeding while using low-dose
      progestin-only contraception. We report the findings of a double-blind,
      randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4
      weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent
      and irregular bleeding while using a levonorgestrel-releasing subdermal
      contraceptive implant. In all women, regardless of treatment, the frequency of
      bleeding decreased significantly over 360 days of observation. Women recorded
      significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone
      treatment than during the 90 days before treatment started. In contrast, the
      duration of bleeding episodes fell more gradually in placebo-treated controls.
      Women using mifepristone were more likely to find treatment acceptable than women
      receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic
      effects may jeopardize contraception, there were no pregnancies. This approach
      may offer a useful strategy to improve continuation rates by alleviating unwanted
      side-effects until bleeding patterns improve spontaneously with time.

PMID- 10966999
TI  - Semen granulocyte elastase: its relevance for the diagnosis and prognosis of
      silent genital tract inflammation.
AB  - Elastase-inhibitor complex was assessed by immunoassay in the seminal plasma of
      312 men attending the outpatient infertility clinic. Using receiver operating
      characteristic (ROC) curve analysis, elastase at the cut-off value of > or =290
      ng/ml was shown to be efficient (sensitivity 79.5%, specificity 74.4%) in the
      detection of genital tract inflammation as defined by leukocytospermia (>1x10(6)
      leukocytes/ml). The prevalence of increased elastase in 292 infertile men was
      significantly higher (34%) as compared with that (5%) observed in 20 fertile men
      (P: = 0.02). Moreover, high elastase concentration (> or =290 ng/ml) was observed
      in 66 of the 264 men (25%) without leukocytospermia. A significant positive
      correlation was found between elastase concentration and patient age (r = 0.202,
      P: < 0.0001) and the number of leukocytes (r = 0.330, P: < 0.0001). A negative
      correlation was found between elastase concentration and semen volume (r = 
      0.146, P: = 0.01) and the percentage of spermatozoa with single-stranded DNA (r =
      -0.194, P: = 0.024), but there was no correlation between elastase and sperm
      reactive oxygen species production. A higher seminal elastase concentration was
      significantly associated with tubal damage in female partners (P: < 0.001). After
      norfloxacine antibiotic therapy, decrease in elastase concentration was observed
      in 15 (25%) of the 60 treated patients. Tubal damage in the partner negatively
      affected the response to antibiotic therapy. In conclusion, granulocyte elastase
      is a reliable screening test for silent genital tract inflammation of the couple.
      The elastase-inhibitor complex may have a protective effect in reducing sperm DNA
      denaturation.

PMID- 10967000
TI  - Follow-up of sperm concentration and motility in patients with lymphoma.
AB  - Lymphomas are a group of diseases, prevalent at reproductive age. Fertility is
      notoriously reduced among lymphoma patients. This study evaluates pre- and post
      treatment semen concentration and motility, and factors associated with semen
      quality deterioration. We followed-up 33 patients with non-Hodgkin's lymphoma or
      with Hodgkin's disease during the years 1987-1997 who were referred for semen
      cryopreservation. Pretreatment semen analysis, and hormonal profile were recorded
      at diagnosis and at least 1 year after completion of the treatment, and compared.
      Medical records for disease type, disease stage and treatment protocols were
      related to long-term sperm outcome. Hormonal concentrations were not predictive
      of post-treatment sperm concentration. In patients with localized disease,
      initial sperm concentration and motility tended to be preserved, compared with
      patients with widespread disease (P: = 0. 016). In Hodgkin's disease patients,
      treatment with the adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)
      protocol was superior to the mechloretamine, vincristine, procarbazine and
      prednisone with ABV protocol regarding germinal toxicity (P: = 0.0008). The post
      treatment sperm outcome was better in patients treated with local irradiation
      than in those who did not undergo irradiation (P: = 0.0027). No predictive tools
      for post-treatment fertility were found and, therefore, every patient with a
      lymphoma should have his semen cryopreserved at diagnosis.

PMID- 10967001
TI  - Is endometrial pre-treatment of value in improving the outcome of transcervical
      resection of the endometrium?
AB  - The aim of this study was to determine whether or not the use of medical pre
      treatment of the endometrium improves the outcome of transcervical resection of
      the endometrium with regards to long-term operative outcome, histological
      findings and patient satisfaction. A prospective randomized trial comparing three
      endometrial pre-treatment agents (danazol, medroxyprogesterone acetate or
      nafarelin) with no pre-treatment was conducted. The main outcome measures were:
      (i) thickness of the endometrium and myometrium resected; (ii) histological stage
      of the endometrium at the time of operation; (iii) the presence or absence of
      menses and (iv) patient satisfaction 1 year post-operatively. Of the three pre
      treatments studied, danazol produced a lower median endometrial thickness than
      the control, showed the greatest ability to induce atrophy of the endometrial
      glands and stroma (not statistically significant) and produced the highest rate
      of amenorrhoea (not different to the control). Danazol and nafarelin produced
      significantly lower median endometrial thickness than no pre-treatment. There
      were, however, no significant differences in the rates of amenorrhoea in any of
      the pre-treatment groups compared with that in the control group. No improvement
      in clinical outcome or patient satisfaction is conferred by the use of medical
      pre-treatments if transcervical resection of the endometrium is performed in the
      proliferative phase of the menstrual cycle.

PMID- 10967002
TI  - Laparoscopic myomectomy and subsequent pregnancy: results in 54 patients.
AB  - The laparoscopic approach to myomectomy has raised questions about the risk of
      uterine rupture in patients who become pregnant following surgery. It has been
      suggested that the rupture outside labour in pregnancies following laparoscopic
      myomectomy can be due to the difficulty of suturing or to the presence of a
      haematoma or to the wide use of radio frequencies. In this paper we describe the
      pregnancy outcome of 54 patients submitted to laparoscopic myomectomy at our
      Institution and prospectively followed during subsequent pregnancies. A total of
      202 patients underwent laparoscopic myomectomy. A total of 65 pregnancies
      occurred in 54 patients who became pregnant following surgery. Data were
      collected about complications of pregnancy, mode of delivery, gestational age at
      delivery and birthweight of the neonates. No cases of uterine rupture occurred.
      Twenty-one pregnancies followed an IVF procedure. Nine patients conceived twice
      and one three times. Four multiple pregnancies occurred. Eight pregnancies
      resulted in a first trimester miscarriage and another in an interstitial
      pregnancy requiring laparotomic removal of the cornual gestational sac. Of the
      remaining 56 pregnancies, 51 (91%) were uneventful. In two cases a cerclage was
      performed at 16 weeks. In two cases pregnancy-induced hypertension developed. Two
      pregnancies ended with a preterm labour (26-36 weeks). A Caesarean section was
      performed in 45 cases (54/57, 80%). In terms of the safety of laparoscopic
      myomectomy in patients who become pregnant following surgery, our results were
      encouraging. However, further studies are needed to provide reliable data on the
      risk factors and the true incidence of uterine rupture.

PMID- 10967003
TI  - In-vitro development of mouse zygotes following reconstruction by sequential
      transfer of germinal vesicles and haploid pronuclei.
AB  - We evaluated whether mouse oocytes reconstructed by germinal vesicle (GV)
      transfer can develop to blastocyst stage. The oocytes were artificially activated
      with sequential treatment of A23187 and anisomycin; fertilization was then
      established by transfer or exchange of pronuclei with those of zygotes fertilized
      in vivo. Type 1 zygotes were constructed by placing the male haploid pronucleus
      from a zygote into the cytoplasm of an oocyte that underwent GV transfer, in
      vitro maturation and activation; for type 2 zygotes, the female pronucleus was
      removed from a zygote and replaced with the female pronucleus of an oocyte
      subjected to GV transfer, in-vitro maturation and activation. Karyotypes of
      activated oocytes and type 2 zygotes were also subjected to analysis. When
      cultured in human tubal fluid (HTF) medium, reconstructed oocytes matured and,
      following artificial activation, consistently developed a pronucleus with a
      haploid karyotype; the activation rate for this medium was two- to three-fold
      higher than that of oocytes cultured in M199 (87% versus 30% respectively).
      Following transfer of a male pronucleus, only 47% of the type 1 zygotes developed
      to morula or blastocyst stage and embryo morphology was poor. In contrast, 73% of
      the type 2 zygotes developed to morula or blastocyst stage, many even hatching,
      with few morphological anomalies. Normal karyotypes were observed in 88% of the
      type 2 zygotes analysed. These observations demonstrate that the nucleus of a
      mouse oocyte subjected to sequential nuclear transfer at GV and pronucleus stages
      is, nonetheless, capable of maturing meiotically, activating normally and
      supporting embryonic development to hatching blastocyst stage. In contrast, the
      developmental potential of the cytoplasm of such oocytes appears to be
      compromised by these procedures.

PMID- 10967004
TI  - Healthy births and ongoing pregnancies obtained by preimplantation genetic
      diagnosis in patients with advanced maternal age and recurrent implantation
      failure.
AB  - Preimplantation genetic diagnosis (PGD) and subsequent embryo development was
      evaluated in 72 couples presenting at our centre for intracytoplasmic sperm
      injection (ICSI) due to severe male factor. The embryo biopsies were performed in
      Ca(2+)/Mg(2+)-free medium. These patients were further divided into those with
      advanced maternal age (AMA, n = 49) and those with recurrent implantation failure
      (RIF, n = 23). Fluorescence in-situ hybridization (FISH) was carried out on 329
      blastomeres (91.3%) with probes for the X, Y, 13, 18 and 21 chromosomes. The
      chromosomal abnormality rate was 41.3% with no significant difference between the
      AMA and RIF groups. Aneuploidy accounted for the majority (72.8%) of chromosomal
      abnormalities. Out of 329 embryos, 84.2% had cleaved after 24 h and 15.1% had
      arrested. Embryos were transferred in 70 patients and 22 pregnancies were
      achieved (31.4% with an ongoing pregnancy rate of 28.5%). There were no
      significant differences between the pregnancy rates of the AMA and RIF groups
      (32.5 and 30% respectively). Therefore PGD should be offered to patients with AMA
      and RIF. Furthermore, the use of Ca(2+)/Mg(2+)-free medium during the blastomere
      biopsy facilitates the procedure, while further embryo cleavage, ongoing
      pregnancies and healthy births are possible.

PMID- 10967005
TI  - Early prediction of severe twin-to-twin transfusion syndrome.
AB  - This extended series of 303 monochorionic twin pregnancies examined at 10-14
      weeks gestation explores the possible association of increased fetal nuchal
      translucency thickness (NT) in the early prediction of severe twin-to-twin
      transfusion syndrome (TTS). Of 303 pregnancies, there were 16 in which at least
      one fetus was structurally or chromosomally abnormal and in the remaining 287
      ongoing pregnancies there were 43 (15%) which developed severe TTS. The median
      fetal NT was 1.0 multiples of the median (MOM) and NT was >95th centile in 47
      (8.2%) fetuses and in at least one fetus in 37 (12.9%) pregnancies. The
      prevalence of increased NT in the pregnancies that developed TTS [17.4% (n = 15)
      of fetuses and 28% (n = 12) of pregnancies] was significantly higher than in the
      non-TTS group [6.6% (n = 32) and 10.2% (n = 25) respectively; Z: = -3.4, P: <
      0.001 and Z: = 3.2, P: < 0.001 respectively], likelihood ratio of increased fetal
      NT for prediction of TTS = 3.5 [95% confidence interval (CI) 1.9-6.2]. In 153 of
      the pregnancies, an ultrasound examination was also performed at 15-17 weeks
      gestation and intertwin membrane folding was seen in 49 (32%) cases; 21 of these
      (43%) subsequently developed TTS compared to two (1.9%) of the 104 pregnancies
      without membrane folding (Z: = 6.6, P: < 0.001), likelihood ratio of membrane
      folding for prediction of TTS = 4.2 (95% CI 3.0-6.0).

PMID- 10967006
TI  - Circulating cytokines and CD30 in normal human pregnancy and recurrent
      spontaneous abortions.
AB  - Concentrations of the T-helper (Th) 1 cytokines interleukin (IL)-2, tumour
      necrosis factor (TNF) -alpha, TNF-beta and interferon-gamma, Th2 cytokines IL-4,
      IL-5, IL-6, IL-10 as well as those of soluble CD30 in sera have been examined
      during the three trimesters of gestation, at delivery in normal pregnancy, and at
      the time of spontaneous abortion in women with a history of unexplained recurrent
      spontaneous abortion (RSA). Significantly higher concentrations of the Th2
      cytokines IL-6 and IL-10 were found at normal delivery than in women with RSA,
      and conversely significantly increased concentrations of the Th1-type cytokine
      TNF-alpha were found in RSA as compared with successful pregnancy. In abortion
      prone women who had a successful pregnancy, significantly higher concentrations
      of IL-6 and significantly lower concentrations of TNF-alpha were found as
      compared with abortion-prone women who had another abortion, supporting the
      notion that Th2- and Th1-bias are associated with successful and unsuccessful
      pregnancy respectively. Serum CD30 concentrations did not correlate with the
      outcome of pregnancy. These findings support observations drawn from experiments
      on the cytokine secretion profiles of peripheral blood mononuclear cells and
      decidual lymphocytes which suggest that normal pregnancy is Th2-biased and that
      unexplained RSA is associated with Th1-type reactivity.

PMID- 10967007
TI  - Permeability of fetal membranes to calcium and magnesium: possible role in
      preterm labour.
AB  - Calcium (Ca(2+)) and magnesium (Mg(2+)) are co-factors in the synthetic activity
      of a variety of enzymes and in the secretory process. Both the binding to fetal
      membranes and the diffusion through the membranes of these two cations could be
      important factors in the synthesis and/or action of prostaglandins and generation
      of nitric oxide (NO) which are believed to regulate myometrial activity
      particularly for the induction of labour. In the present study, the permeability
      to Ca(2+) and Mg(2+) of chorioamniotic membranes obtained from women who had
      undergone term or preterm labour was examined. Diffusion of Ca(2+) and Mg(2+)
      were measured using a system of Plexiglas chambers separated by the mounted fetal
      membrane. Permeability of Mg(2+) and Ca(2+) through fetal membranes was
      calculated using non-linear regression analysis. The data show highly significant
      differences in the diffusion of Ca(2+) and Mg(2+) across fetal membranes between
      preterm and term labour. Transport coefficient K for Ca(2+) was 0.203 h(-1) and
      0. 0223 h(-1) in term and preterm labour respectively. The corresponding values
      for Mg(2+) were -0.017 h(-1) and 0.051 h(-1) respectively. It is proposed that a
      considerable reduction in Ca(2+) available to myometrium and placenta would
      result in down-regulation of nitric oxide synthase (NOS) activity and thereby a
      reduction in NO production. This together with an effect on intracellular Ca(2+)
      transport resulting from a reduced availability of Mg(2+) would lead to increased
      myometrial activity in preterm labour.

PMID- 10967008
TI  - Pregnancy outcome and infant follow-up of fetuses with abnormally increased first
      trimester nuchal translucency.
AB  - The numbers of fetuses with an abnormal increased first trimester nuchal
      translucency (NT) but a confirmed normal anatomy and karyotyping is relatively
      small and therefore a challenge for prenatal counselling. The aim of the current
      study was to assess the long-term pregnancy outcome and infancy prognosis of 78
      fetuses with NT > 95th centile of the normal range for crown-rump length (CRL).
      The most common abnormalities in this group were aneuploidy, which affected 32 of
      the fetuses followed by four and three cases which were miscarried or had cardiac
      defects respectively. The remaining euploid fetuses with normal detailed scans
      were followed throughout their infancy (mean 24 months; range 12-36 months). Post
      natally, except for a correctable case of ventricular septal defect and a case of
      posterior urethral valve, no other abnormalities were detected. After excluding
      all aneuploid cases and using the maternal age as a second variable, an
      uncomplicated pregnancy outcome could be anticipated in 17 cases (100%) when the
      maternal age was <30 years and NT between 95th centile and 5 mm. However, the
      chance of a normal outcome dropped to 50% in four cases with maternal age > or
      =30 years and NT > or =5 mm (Fisher's exact test; P: = 0.02). These findings
      suggest that the long-term prognosis of the euploid fetuses with large NT (<5 mm)
      is reassuring in younger women.

PMID- 10967009
TI  - Maternal serum inhibin A concentrations in early pregnancy after IVF and embryo
      transfer reflect the corpus luteum contribution and pregnancy outcome.
AB  - To compare maternal serum inhibin A concentrations in early pregnancy with
      pregnancy outcomes and treatment protocols, serum samples were collected from 237
      women undergoing in-vitro fertilization (IVF) and embryo transfer cycles. Samples
      were collected on day 16 after oocyte retrieval for beta human chorionic
      gonadotrophin (HCG) pregnancy testing and inhibin A measurement. The samples were
      divided into non-pregnant (n = 128) and pregnant (n = 109) groups, the
      pregnancies were followed and outcomes determined. Inhibin A concentrations were
      significantly lower in non-pregnant women than in women with ongoing pregnancies
      (P: < 0.001) and those resulting in spontaneous abortions (P: < 0.001). In
      ongoing pregnancies, inhibin A concentrations were significantly lower in the
      absence of functioning ovaries (donor oocyte/embryo) (P: < 0.01) and in natural
      cycles (frozen-thawed embryo transfer) (P: < 0.01) compared with concentrations
      after ovarian stimulation. Further, since inhibin A concentrations were not
      significantly different between singleton and multiple pregnancies in the ovarian
      stimulation protocol, the size of the early trophoblast does not appear to
      influence the secretion of inhibin A. These data strongly support the concept
      that the corpus luteum is a major source of circulating inhibin A in early
      pregnancy. Additionally, low concentrations of serum inhibin A may be useful in
      predicting betaHCG-positive preclinical 'biochemical' pregnancies.

PMID- 10967010
TI  - Longitudinal analysis of maternal plasma leptin concentrations during normal
      pregnancy and pre-eclampsia.
AB  - Leptin concentrations have been found to be elevated in cross-sectional studies
      of established pre-eclampsia. Circulating concentrations of leptin were measured
      in a cross-sectional study to confirm these findings (19 women with pre-eclampsia
      and 13 normal pregnant controls) and in a longitudinal study to establish the
      timing of the increase in leptin concentrations (samples obtained at 16, 20, 24,
      28, 32, 36 and 38 weeks gestation from eight women who went on to develop pre
      eclampsia and seven normal pregnant controls). In the cross-sectional study,
      plasma leptin concentrations were significantly greater in women with pre
      eclampsia than in normal controls (P: = 0.001). In the longitudinal study, it was
      found that circulating leptin concentrations rose gradually to 32 weeks and
      thereafter declined slightly in normals. The concentrations in women destined to
      develop pre-eclampsia were consistently higher from 20 weeks gestation (P: = 0.04
      0.003) and, in contrast to the normal controls, rose markedly from 32 weeks as
      pre-eclampsia developed. This study confirms that plasma leptin concentrations
      are increased in established pre-eclampsia and reports for the first time that
      leptin concentrations are elevated before pre-eclampsia is clinically evident.

PMID- 10967011
TI  - Laparoscopic therapy of an intact primary ovarian pregnancy with ovarian
      hyperstimulation syndrome: case report.
AB  - A case of an intact primary ovarian pregnancy with ultrasonographic demonstration
      of heart motion following ovarian stimulation is presented. After preoperative
      ultrasonographic confirmation of an extrauterine pregnancy, proof of the ovarian
      localization was achieved by intra-operative ultrasonographic visualization
      during a diagnostic laparoscopy on post-menstrual day 48. A moderate ovarian
      hyperstimulation syndrome with a concomitant increase in size, vulnerability and
      vascularity of the ovaries presented an additional challenge for the surgical
      approach. However, thanks to the early diagnosis of the ectopic pregnancy
      localization, a laparoscopic organ-preserving removal of the intact ovarian
      pregnancy was successfully performed. In this way, the fertility of the patient,
      who had previously undergone contralateral ovariectomy, was preserved. To our
      knowledge, this represents the first such treatment to be reported in the medical
      literature. Improvements in diagnosis and therapy of ovarian pregnancy are
      reviewed.

PMID- 10967012
TI  - What does it mean to be a donor offspring? The identity experiences of adults
      conceived by donor insemination and the implications for counselling and therapy.
AB  - In the absence of research with adult donor offspring, this study begins to
      bridge that gap by asking individuals about their experiences as donor offspring
      and considering the implications for psychotherapeutic and counselling practice.
      Sixteen participants (13 male, three female, age range 26-55 years) recruited
      through donor insemination support networks in the UK, USA, Canada and Australia,
      were sent semi-structured questionnaires by E-mail and post. Using identity
      process theory as a framework for understanding participants' accounts, the data
      were qualitatively analysed using interpretative phenomenological analysis.
      Participants consistently reported mistrust within the family, negative
      distinctiveness, lack of genetic continuity, frustration in being thwarted in the
      search for their biological fathers and a need to talk to a significant other
      (i.e. someone who would understand). These experiences could be postulated as
      being indicative of a struggle to assimilate, accommodate and evaluate
      information about their new identities as donor offspring. Psychotherapists and
      counsellors need to be aware of these identity issues if they are to meet the
      needs of donor offspring within therapeutic practice.

PMID- 10967013
TI  - Disclosure of donor insemination to the child: the impact of Swedish legislation
      on couples' attitudes.
AB  - The question whether or not parents of children conceived after donor
      insemination (DI) tell their offspring about its biological background was
      addressed. Swedish legislation from 1985 gives the child born after DI the right,
      when grown up, to receive identifying information about the sperm donor. Until
      now no information about compliance with the law has been available. All parents
      who gave birth to a child by DI after the new legislation in two major Swedish
      fertility centres (Stockholm and Umea) received a questionnaire containing
      questions about the issue of informing the child. The response rate was 80%. The
      majority of parents (89%) had not informed their children, whereas 59% had told
      someone else. As a response to an open question, 105/132 parents chose to comment
      on their answer about not having informed their child. Of these families, 61
      intended to tell their child later, 16 were not sure and 28 were not going to
      inform the child. Compliance with the law must be regarded as low since only 52%
      of the parents had told or intended to tell their child. In addition, concern is
      raised about the children who run the risk of being informed by someone other
      than their parents.

PMID- 10967014
TI  - Telomerase activity in testicular biopsy material.

PMID- 10967015
TI  - Use of GnRH in preference to LH-RH terminology in scientific papers.

PMID- 10967016
TI  - The epitope detected by cytotoxic T lymphocytes against thymus leukemia (TL)
      antigen is TAP independent.
AB  - Thymus leukemia (TL) antigens belong to the family of MHC class Ib antigens. We
      have shown in our previous studies that they serve as transplantation antigens,
      and can be recognized by both TCR alpha beta and TCR gamma delta cytotoxic T
      lymphocytes (CTL) with TL but not H-2 restriction. Although TL are known to be
      expressed TAP independently, it is unclear whether peptide loading on TL
      molecules is necessary for the formation of CTL epitopes. In the present study,
      we first showed that TL expression is beta(2)-microglobulin (beta(2)m)-dependent
      but TAP1 independent by flow cytometric analysis of thymocytes from beta(2)m- or
      TAP1-deficient mice crossed with TL transgenic mice expressing Tla(a)-3-TL on
      their thymocytes. Subsequently, we investigated the epitope recognized by CTL
      derived from C3H mice immunized with skin from a transgenic mouse expressing
      T3(b)-TL ubiquitously. Bulk CTL lines against TL from primary mixed lymphocyte
      cultures showed comparable cytotoxicity against T3(b)-TL transfectants of TAP2
      deficient murine RMA-S grown at 37 degrees C to that against those grown at 25
      degrees C. Furthermore, TCR alpha beta and TCR gamma delta CTL clones against TL
      recognized TL expressed on T3(b)-TL transfectants of RMA-S and Drosophila
      melanogaster cells having broad defects in peptide loading of MHC, and lysed
      these target cells. These results together indicate that TL-specific CTL
      populations primarily recognize epitopes expressed TAP independently.

PMID- 10967017
TI  - Early in vitro priming of distinct T(h) cell subsets determines polarized growth
      of visceralizing Leishmania in macrophages.
AB  - An in vitro priming system of murine naive splenocytes was established to
      investigate early immune responses to Leishmania chagasi, the agent of visceral
      leishmaniasis in the New World. Priming of splenocytes from resistant C3H and CBA
      or susceptible BALB and B10 mice with L. chagasi resulted in blast transformation
      and in proliferating parasite-specific CD4(+) T cells secreting a differential
      complement of cytokines (IFN-gamma and low IL-10 levels for resistant T cells;
      IFN-gamma, IL-4 and high IL-10 levels for susceptible T cells). After priming,
      intracellular parasite load was much higher in susceptible than in resistant-type
      splenocyte cultures. On the other hand, infection of purified splenic macrophages
      from either resistant or susceptible mice with live L. chagasi promastigotes,
      resulted in comparable parasite loads. Moreover, when early CD4(+) T cell priming
      in splenocyte cultures was disrupted with anti-CD4 mAb, polarized parasite growth
      was abolished, becoming comparable in resistant and susceptible cultures.
      Neutralizing IL-4 activity during splenocyte priming did not affect the final
      parasite load in susceptible cultures. However, neutralizing IL-10 activity
      markedly decreased parasite load in susceptible, but not in resistant splenic
      macrophages. These results suggest that IL-10 plays an important role in L.
      chagasi infection in susceptible hosts. The results also indicate that innate
      control of growth of a visceralizing Leishmania in splenic macrophages results
      from the ability to activate different CD4(+) T cell subsets.

PMID- 10967018
TI  - Adenoids provide a microenvironment for the generation of CD4(+), CD45RO(+), L
      selectin(-), CXCR4(+), CCR5(+) T lymphocytes, a lymphocyte phenotype found in the
      middle ear effusion.
AB  - Adenoidectomy in children with otitis media with effusion reduces inflammation in
      the middle ear by an unknown mechanism. Potentially, the adenoids of these
      children may serve as a site for the differentiation of lymphocytes, which after
      entering blood circulation eventually extravasate in the middle ear mucosa and
      thereby contribute to excessive inflammation. During lymphocyte extravasation
      various adhesion molecules and chemokines play a crucial role. To evaluate
      possible connections between the adenoids and middle ear inflammation, the
      expression of the chemokine receptors CXCR4 and CCR5 and the lymphocyte homing
      receptor L-selectin were analyzed in adenoidal and middle ear lymphocytes. It was
      found that most CD4(+) T lymphocytes in the middle ear effusion express the
      memory phenotype marker CD45RO and the chemokine receptors CXCR4 and CCR5, but
      are negative for the lymphocyte homing receptor L-selectin. This cell phenotype
      was rare in peripheral blood but was found much more frequently in the adenoids.
      The results suggest that the adenoids provide a microenvironment for the
      generation for CD4(+), CD45RO(+), L-selectin(-), CXCR4(+) and CCR5(+) T
      lymphocytes. Further, these cells may include cells that have the capacity to
      home to the middle ear mucosa. As the adenoidal CD4(+) memory phenotype CD45RO(+)
      T cells expressed the activation antigen CD69 and included cells expressing the
      HIV co-receptors CXCR4 and CCR5 at a high level, they may be permissive for HIV
      infection.

PMID- 10967019
TI  - Strand bias in Ig somatic hypermutation is determined by signal sequence within
      the variable region.
AB  - Ig genes undergo hypermutation with a nucleotide preference of A over T for
      mutation on the coding strand. As only with concomitant strand bias can such
      nucleotide bias be observed, Ig gene hypermutation is generally accepted as a
      strand-specific process, for which the mechanistic basis remains unknown. It has
      previously been shown that different non-Ig sequences replacing the LVJ region of
      an Ig transgene to various extents are targeted for hypermutation with similar
      mutation frequencies. However, the nucleotide bias characteristic of Ig
      hypermutation was not found in two of the three such sequences studied. To test
      whether it is the DNA sequences of the non-Ig substrates that determine the
      pattern of nucleotide bias in hypermutation or whether the LVJ sequence may
      contain element(s) that confer strand bias, we have added back all the replaced
      LVJ sequences to one of the transgenes, L(kappa)-Vgpt*, that expresses no strand
      bias in hypermutation and studied the outcome. The results show that the gpt
      sequence in the presence of the complete LVJ sequence hypermutates differently
      from the same sequence in L(kappa)-Vgpt* where 84% of the LVJ was replaced. The
      main difference is the resumption of strand bias characteristic of Ig
      hypermutation. Thus, whether or not a substrate sequence manifests strand bias in
      hypermutation is not inherently determined by the substrate DNA sequence. This
      indicates the presence of special element(s) within the LVJ that confer strand
      bias.

PMID- 10967020
TI  - Reconstitution of conformationally dependent epitopes on the N-terminal
      extracellular domain of the human muscle acetylcholine receptor alpha subunit
      expressed in Escherichia coli: implications for myasthenia gravis therapeutic
      approaches.
AB  - Myasthenia gravis (MG) is an autoimmune disease, caused by autoantibodies against
      the muscle acetylcholine receptor (AChR), an oligomeric transmembrane
      glycoprotein composed of alpha(2)beta gamma delta subunits. The alpha subunit
      carries in its N-terminal extracellular domain the main immunogenic region (MIR),
      a group of conformationally dependent epitopes that seems to be a major target
      for the anti-AChR antibodies in MG patients. Detailed epitope studies on
      pathogenic anti-AChR antibodies have been hindered because the binding of most of
      these antibodies is conformationally dependent, which precludes the use of
      denatured AChR fragments. The N-terminal extracellular fragment, residues 1-207,
      of the human AChR alpha subunit was expressed in Escherichia coli in a denatured
      form, solubilized in a guanidinium hydrochloride-containing buffer, purified, and
      renatured using a refolding approach which employs a detergent and a cyclodextrin
      as 'artificial chaperones'. Compared with the non-refolded protein, the refolded
      molecule exhibited a dramatic improvement in terms of the binding of all anti-MIR
      mAb tested. Anti-MIR mAb that normally bind weakly to the denatured alpha subunit
      bound approximately 30-100 times better to the refolded polypeptide and other
      anti-MIR mAb that bind exclusively to completely conformationally dependent
      epitopes also bound quite efficiently. These results, in addition to providing a
      means for the thorough investigation of the antigenic structure of the AChR, show
      that the conformationally dependent MIR epitopes do not require the participation
      of the oligosaccharide moiety of the alpha subunit nor the contribution of
      neighboring subunits for antibody binding. Such AChR fragments may be used in
      structural studies of the AChR autoantigen, and should prove valuable in the
      understanding and development of therapeutic approaches for MG.

PMID- 10967021
TI  - CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective
      immunity against infection with Leishmania major.
AB  - The roles of gamma delta T, NK and NKT cells in an early stage of protective
      immunity against infection with Leishmania major were investigated. Further, the
      contribution of these innate cells to the expression of 65 kDa heat shock protein
      (HSP65) in host macrophages was examined, since we found previously that this
      expression prevents apoptotic death of infected macrophages and is a crucial step
      in the acquisition of protective immunity against infection with various obligate
      intracellular protozoa including L. major. C57BL/6 and DBA/2 mice were found to
      be resistant against the infection on the basis of the parasite burden in their
      regional lymph nodes, and to strongly express HSP65 in their macrophages, whereas
      BALB/c mice were susceptible and barely expressed the HSP65. In those resistant
      mice, CD4(+) NKT cells prominently increased in their regional lymph node and
      were the main effector cells at least for an early stage of the protective
      immunity and for the HSP65 expression, whereas this subset did not increase in
      susceptible BALB/c mice. Further, neither gamma delta T nor NK cells in resistant
      mice contributed to those protective immune responses. The NKT cell subset bore
      CD3, CD4, TCR alpha beta, IL-2R beta and NK1.1 but scarcely asialo-GM(1).
      Moreover, this effector subset was confirmed to be V(alpha)14 NKT cells by using
      J(alpha)281(-/-) mice.

PMID- 10967022
TI  - Correlation of anti-viral B cell responses and splenic morphology with expression
      of B cell-specific molecules.
AB  - This study attempted to evaluate and compare the role of various B cell-specific
      markers for anti-viral immune responses in mouse strains lacking molecules
      belonging to the B cell receptor (BCR) complex (IgM, Ig alpha and C(kappa)), the
      co-stimulatory molecules (CD19 and CD22), the protein kinases [Bruton's tyrosine
      kinase (Btk)] or the transcription factors (OBF-1). These mice were tested in two
      model infections [vesicular stomatitis virus (VSV) and lymphocytic
      choriomeningitis virus (LCMV)] using T cell-independent (TI) or T cell-dependent
      (TD) antigens. All mice controlled an LCMV infection indicating that cytotoxic T
      cell functions were within normal ranges. In contrast, OBF-1(-/-) mice were
      partially protected and mb-1(delta c/delta c) mice not at all protected against
      VSV infection, a virus that is controlled virtually exclusively by neutralizing
      antibodies. Susceptibility to VSV infection was correlated with structural
      defects in the spleen: absence of mature B cells and follicles with marginal zone
      macrophages and absence of germinal centers with follicular dendritic cells
      correlated with lack or substantial reduction of protective IgM and IgG responses
      respectively. The lack of kappa light chain did not affect the neutralizing
      response, indicating that it could easily be replaced by the lambda chain.
      Absence of the co-stimulatory molecules CD19 and CD22 or of the signaling
      molecule Btk had modulating effects, but did not increase susceptibility to VSV
      or LCMV. Our findings suggest that there are crucial molecules for B cell
      activation at the beginning (BCR complex) and the end (transcription) of the
      signaling cascade, whereas fine-tuning factors modulating the response in between
      exhibit considerable functional overlap.

PMID- 10967023
TI  - Activation-dependent modulation of B lymphocyte migration to chemokines.
AB  - In this study we have examined the migration responses of human peripheral blood
      or tonsillar B lymphocytes to a selection of 27 chemokines. Freshly isolated
      (CD19(+)) B lymphocytes show greatly impaired in vitro chemotaxis which is
      overcome by overnight culture. The best responses of cultured B lymphocytes were
      observed with BCA-1, SLC, ELC and SDF-1, reaching 19-26% of total input cells
      that have migrated, followed by LARC and TECK with 5-10% of migrated cells,
      whereas no other chemokine was found to be active. Stimulation of B lymphocytes
      with lipopolysaccharide or anti-CD40 plus IL-4 resulted in marked enhancement of
      the migration response to BCA-1, SLC, ELC and SDF-1, reaching 30-60% migrated
      cells at 12 or 36 h of culture respectively. The activation-dependent increase in
      the migration efficacy was transient and declined to base level responses after
      72 h of culture. Under no circumstances did we detect B lymphocyte chemotaxis to
      inflammatory chemokines. Also, mobilization of intracellular calcium
      ([Ca(2+)](i)), an otherwise typical response of leukocytes to chemokines, was not
      observed. The transient increase in B lymphocyte migration did not correlate with
      changes in chemokine receptor expression, as evidenced by cell surface staining
      with antibodies to CXCR4, CXCR5 and CCR6, and by receptor transcript analyses.
      BCA-1, SLC, ELC and SDF-1 are typical 'housekeeping' chemokines with prominent
      expression at discrete locations in lymphoid tissues. Modulation of migration to
      these chemokines may be a critical mechanism for the proper positioning of B
      lymphocytes during humoral responses in secondary lymphoid tissues.

PMID- 10967024
TI  - Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by
      HLA-A2 heavy chain modifications.
AB  - Vigorous HIV-1-specific CD8(+) cytotoxic T lymphocyte (CTL) responses play an
      important role in the control of HIV-1 replication and the induction of a strong,
      broadly cross-reactive CTL response remains an important goal of HIV vaccine
      development. It is known that the display of high levels of class I MHC-viral
      peptide complexes at the cell surface of target cells is necessary to elicit a
      strong CTL response. We now report two strategies to enhance the presentation of
      defined HIV-1 epitope-specific CTL target structures, by incorporating
      subdominant HIV-1 reverse transcriptase (RT) CTL epitope sequences into the human
      class I MHC molecule HLA-A2. We show that either incorporation of HIV-1 CTL
      epitopes into the signal sequence of HLA or tethering of epitopes to the HLA-A2
      heavy chain provide simple ways to create effective CTL target structures that
      can be recognized and lysed by human HLA-A2-restricted RT-specific CD8(+) CTL.
      Moreover, cells expressing these epitope-containing HLA-A2 constructs stimulated
      the generation of primary epitope-specific CTL in vitro. These strategies offer
      new options in the design of plasmid DNA-based vaccines or immunotherapeutics for
      the induction of CTL responses against subdominant HIV-1 epitopes.

PMID- 10967025
TI  - Presence of the 55 kDa glycosylation inhibiting factor in human serum.
AB  - An ELISA system for the human glycosylation inhibiting factor (GIF) was
      established using polyclonal antibodies against highly purified 13 kDa
      recombinant human GIF, and the concentration of GIF in the sera of healthy donors
      and patients with various diseases was determined. GIF was detected in the sera
      of most healthy individuals and its concentration tended to increase with age. It
      was also found that the serum GIF levels markedly increased in some patients with
      rheumatoid arthritis or malignant tumors. Analysis of serum samples by SDS-PAGE
      and immunoblotting revealed a 55 kDa protein that has both the GIF antigenic
      determinant and the TCR alpha chain determinant. A 13 kDa GIF was not detected in
      the sera. In view of our previous findings on antigen-specific GIF from murine
      suppressor T cell hybridomas indicating that the 55 kDa GIF is a post
      translationally formed conjugate of a TCR alpha chain with 13 kDa GIF, we suspect
      that the 55 kDa GIF detected in human sera is a human homologue of the murine 55
      kDa GIF.

PMID- 10967026
TI  - Influence of nucleotide polymorphisms in the CCR2 gene and the CCR5 promoter on
      the expression of cell surface CCR5 and CXCR4.
AB  - Polymorphisms in the CCR2 gene (CCR2-64I) and the CCR5 promoter (pCCR5-59029G)
      have been correlated with slower HIV-1 disease progression. How these
      polymorphisms influence the rate of AIDS progression has remained unclear. We
      have therefore investigated whether these nucleotide polymorphisms will reduce
      the expression levels of surface CCR5 and CXCR4, and thus lead to slower AIDS
      progression. For this, a cohort of Chinese volunteers in Taiwan was subjected to
      the determination of CCR2 and pCCR5 genotypes followed by analysis of the surface
      CCR5 and CXCR4 expression on five cell types derived from peripheral blood
      mononuclear cells by flow cytometry. Several significant associations were
      detected between genotypes and expression levels of the proteins. The most
      important finding was that an increased number of CD4(+) cells expressing CCR5
      correlated with pCCR5-59029A homozygosity without the interference of both the
      CCR2-64 and the CCR5 delta 32 (deleted 32 bp) mutations (P: = 0.0453), which is
      consistent with the previous data on the association of the genotype to AIDS
      progression. Since different genetic polymorphisms co-exist in human beings, the
      rate of AIDS progression as well as the risk of rheumatoid arthritis may be
      governed by the interplay of the array of nucleotide changes and their affected
      proteins.

PMID- 10967027
TI  - Rotational and lateral dynamics of I-A(k) molecules expressing cytoplasmic
      truncations.
AB  - Rotational and lateral diffusion of I-A(k) molecules with various alpha and beta
      chain cytoplasmic truncations known to affect class II function were measured to
      assess the role of cytoplasmic domains in regulating I-A(k) molecular motions.
      Deletion of all 12 alpha chain C-terminal residues and all 18 corresponding beta
      chain residues (alpha-12/beta-18) is known to abrogate translocation of protein
      kinase C to the nucleus upon class II cross-linking. Similarly, truncation of the
      entire cytoplasmic alpha chain domain and the 10 C-terminal residues of the beta
      chain impairs presentation of antigenic peptides to T cells. The rotational
      correlation time of the wild-type molecule, 11.9 +/- 2.6 micros as measured by
      time-resolved phosphorescence anisotropy, decreased to 7. 2 +/- 3.7 micros in the
      fully truncated alpha-12/beta-18 protein. Other truncated class II molecules
      exhibited only small changes in molecular rotation rates relative to the wild
      type. The rate of lateral diffusion of the fully truncated molecule, measured
      with two independent methods, 2.3 x 10(-10) cm(2)/s, was comparable with that of
      the wild-type molecule. Thus, it appears that the alpha and beta chain
      cytoplasmic domains regulate the molecular motions of unperturbed I-A(k)
      molecules only modestly, despite the known involvement of these regions in class
      II signaling. Various explanations for this behavior are discussed, e.g. the
      possibility that class II membrane complexes are sufficiently large that
      association and dissociation of specific signaling proteins during antigen
      presentation do not significantly perturb the apparent molecular motions of the
      complex.

PMID- 10967028
TI  - Cytokines and chemokines are both expressed by human myoblasts: possible
      relevance for the immune pathogenesis of muscle inflammation.
AB  - The idiopathic inflammatory myopathies are characterized by antibody- or cell
      mediated immune response against unknown muscle tissue antigens. In these
      diseases a cellular infiltrate, composed of T and B lymphocytes, macrophages and
      NK cells, may invade muscle tissue with a gradient from the perivascular space to
      the endomysial compartment. Muscle cells may be actively involved in the
      processes of mononuclear cell recruitment and activation from the blood stream to
      the areas of inflammation. In order to verify this hypothesis, cultured human
      myoblasts were tested for their capacity to express different pro-inflammatory
      cytokines [IL-1alpha, IL-1beta, IL-6 and tumor necrosis factor (TNF)-alpha] and
      chemokines (IL-8, MCP-1 and RANTES) at the mRNA level and protein secretion, in
      the presence of the pro-inflammatory cytokines IFN-gamma and TNF-alpha alone or
      in combination. We confirmed that human myoblasts expressed IL-1alpha and IL-6
      constitutively, while IL-1beta and TNF-alpha are detected only after treatment
      with pro-inflammatory cytokines; moreover, we observed that TNF-alpha was
      expressed on an autocrine fashion by myoblasts. IL-8 and RANTES were expressed
      constitutively while MCP-1 after proper induction. These molecular data were
      further confirmed by specific ELISA in the supernatant from cultured myoblasts.
      Our results underline the importance of human myoblasts in the recruitment of
      leukocytes from the blood stream and, most probably, in the cross-talk between
      infiltrating inflammatory cells and muscle cells, creating the conditions for a
      chronic inflammation. Moreover, the capacity of muscle cells to behave as cells
      of the immune system has to be kept in mind, also in view of i.m. vaccination and
      use of molecular engineered myoblasts as vehicles in gene therapy.

PMID- 10967029
TI  - T(h)1 versus T(h)2 cytokine profile determines the modulation of in vitro T cell
      independent type 2 responses by IL-4.
AB  - We have previously demonstrated that stimulation of B cells by multivalent
      membrane Ig cross-linking, using dextran-conjugated anti-IgD mAb (alpha delta
      dex), in the presence of cytokines, is an in vitro model for T cell-independent
      type 2 (TI-2) Ig secretory responses. Earlier studies have shown that IL-4
      enhances IgM secretion upon stimulation with alpha delta-dex plus IL-5 and
      induces IgG1 isotype-switching, without altering the proliferative response to
      alpha delta-dex. Here we show that IL-4 can have both stimulatory and inhibitory
      effects on alpha delta-dex-induced Ig secretion. Both the kinetics and time of
      exposure to IL-4, and the nature of the cytokine additions, T(h)1 versus T(h)2,
      determine whether stimulation or inhibition is observed. Preincubation of sort
      purified B cells with IL-4 caused a 6- to 8-fold increase in Ig secretory
      responses to subsequent stimulation with alpha delta-dex plus IL-1, IL-2 or a
      combination of both. However, the continued presence of IL-4 during B cell
      stimulation suppressed responses to all cytokine combinations tested, except for
      those which included IL-5. Of 11 cytokines tested, only IL-4 showed this dual
      effect of enhancement and suppression. The stimulatory effect of IL-4 required a
      minimum of 4 h of preincubation and could be inhibited by the addition of IFN
      gamma. Thus stimulation of non-MHC class II-dependent T or non-T cells by
      multivalent antigens to secrete IL-4 may regulate the response to these antigens,
      such that early and brief exposure of B cells to IL-4 will enhance a subsequent
      TI-2 response in the presence of T(h)1-dependent cytokines, while continuous
      exposure will result in inhibition of the response.

PMID- 10967030
TI  - Activation-induced expression of murine CD83 on T cells and identification of a
      specific CD83 ligand on murine B cells.
AB  - Human CD83 is a cell surface protein expressed predominantly by dendritic cells
      (DC) and lymphoid cells. So far, there exists no information on the function and
      distribution of mCD83. Here we demonstrate that mCD83 is moderately expressed on
      resting T cells and DC, but strongly increases in its expression on T cells
      following activation with antigenic peptides or T cell receptor-specific mAb.
      When returning to the resting state, T cells down-regulate CD83 again. Ig fusion
      proteins which express the extracellular part of the mCD83 molecule (mCD83-Ig)
      specifically inhibit antigen-specific T cell proliferation and IL-2 secretion in
      spleen cell cultures from DO11.10 T cell receptor transgenic mice. Staining of
      spleen cells from BALB/c, XID and mu MT (B cell) knockout mice with mCD83-Ig
      proteins reveals the presence of a CD83 ligand predominantly expressed most
      likely by B220(+) cells since spleen cells from mu MT knockout mice do not bind
      mCD83-Ig. CD83, besides its established expression on human dendritic cells,
      thus, also represents a new marker molecule on activated T cells which with its
      specific ligand is involved in the regulation of T cell responses.

PMID- 10967031
TI  - Affinity of thymic self-peptides for the TCR determines the selection of CD8(+) T
      lymphocytes in the thymus.
AB  - Experiments with synthetic antigen peptides have suggested that a critical
      parameter that determines the developmental fate of an immature thymocyte is the
      affinity of interaction between TCR and self-peptide/MHC expressed on thymic
      stromal cells. To test the physiological relevance of this model for thymocyte
      development, we determined the affinity of the anti-HY TCR (B6.2.16) expressed on
      CD8(+) cells for thymic self-peptide/H-2D(b) tetramers, then examined the ability
      of these self-peptides to determine the outcome of B6.2.16 CD8 cell selection in
      the thymus. The B6.2.16 TCR bound the male HY self-antigen with high affinity.
      Thymic self-peptides, which are highly abundant on the surface of thymic
      epithelial cells, bound the B6.2.16 TCR with low affinity. The ability of self
      peptides to trigger positive or negative selection of B6.2.16 CD8 cells in
      cultured fetal thymi was determined by the relative affinity of self-peptide/H
      2D(b) for the B6.2.16 TCR. High-affinity binding of the HY self-peptide resulted
      in B6.2.16 TCR complex zeta chain phosphorylation and the negative selection of
      B6.2.16 CD8 cells. Low-affinity binding of thymic self-peptides to B6.2.16 TCR
      resulted in the positive selection of B6.2.16 CD8 cells. Differences between the
      binding affinities of self-peptides to B6.2.16 TCR accounted for the self-peptide
      specificity of B6.2.16 CD8 cell positive selection. We conclude that the relative
      affinity of TCR for thymic self-peptide/class I MHC is a critical parameter in
      determining fate of CD8(+) cells during thymic selection.

PMID- 10967032
TI  - Monocyte inflammatory protein-1 alpha facilitates priming of CD8(+) T cell
      responses to exogenous viral antigen.
AB  - Dendritic cells (DC) derived from bone marrow precursors of BALB/c or C57BL/6
      mice in low-serum cultures supplemented with granulocyte macrophage colony
      stimulating factor and Flt(3) ligand were pulsed in vitro with hepatitis B
      surface antigen (HBsAg) particles. DC processed exogenous HBsAg and presented its
      MHC class I-binding epitopes to cytotoxic T lymphocytes (CTL). This specific and
      restricted interaction of DC with CTL stimulated release of IFN-gamma and
      macrophage inflammatory protein (MIP)-1 alpha from the responding CTL. MIP-1
      alpha enhanced the survival of DC in vitro but did not induce proliferation.
      Furthermore, co-delivery of MIP-1 alpha facilitated CTL priming in vivo to
      exogenous HBsAg in low responder C57BL/6 (H-2(b)) mice: a single injection of a
      low dose of HBsAg particles (without further adjuvants) successfully primed K(b)
      restricted CTL responses to HBsAg only when the exogenous antigen was co
      delivered with 100 ng MIP-1 alpha. These in vitro and in vivo data point to an
      important role of MIP-1 alpha in the DC-dependent priming of CTL to exogenous
      viral antigens.

PMID- 10967033
TI  - Ocular gene therapy: quo vadis?

PMID- 10967034
TI  - Astrocytes and blood vessels define the foveal rim during primate retinal
      development.
AB  - PURPOSE: To investigate the relationship between development of the perifoveal
      blood vessels and formation of the foveal depression. METHODS: Retinal sections
      and flatmounts from monkeys aged between fetal day (Fd)80 and 2 years of age were
      double labeled using antisera to CD31 or von Willebrand factor to detect vascular
      endothelial cells and antiserum to glial fibrillary acidic protein to detect
      astrocytes. Sections were studied by fluorescence or confocal microscopy.
      RESULTS: From Fd88 to 115, vessels on the horizontal meridian were found only at
      the level of the ganglion cell layer (GCL)-inner plexiform layer (IPL) border
      where they form the ganglion cell layer plexus (GCP). Stellate astrocytes
      accompany GCP vessels and extend closer to the fovea than vessels. The foveal
      avascular zone was present within the GCP at Fd101, and at Fd105 a shallow foveal
      depression encircled by the GCP was present. The GCP foveal margin had the same
      dimensions as the adult foveal pit. Both blood vessels and astrocytes were
      excluded from the emerging fovea throughout development. After Fd140, capillary
      plexuses in the outer retina anastomosed with the GCP on the foveal slope to form
      a perifoveal plexus, but this plexus did not mature until a month or more after
      birth. After Fd142, astrocytes rapidly disappeared from the GCP and most of
      central retina. CONCLUSIONS: An avascular area is outlined by the GCP before the
      foveal pit begins to form, suggesting that molecular factors in this region
      exclude both vessels and astrocytes. These factors may also guide neuronal
      migration to form the pit. Because the perifoveal plexus is formed during late
      gestation, both capillary growth and foveal development may be affected adversely
      by prematurity.

PMID- 10967035
TI  - Cyclin-dependent kinase inhibitory protein expression in human choroidal melanoma
      tumors.
AB  - PURPOSE: Recent studies have demonstrated the close link between oncogenesis and
      cell cycle machinery. Cyclin-dependent kinase inhibitory proteins (CKIs) have
      been shown to play a critical role in the regulation of cell cycle progression.
      Alteration of CKI levels and/or functions could be implicated in cell
      transformation. The three CKIs-p16, p21, and p27-were investigated in human uveal
      melanoma tumors, and an attempt was made to correlate their levels with
      clinicopathologic parameters, as well as to p53 and Ki-67 (Mib-1) protein levels.
      METHODS: Immunochemistry was performed on 32 formalin-fixed, paraffin-embedded
      specimens of malignant choroidal melanoma. Immunoblot was performed to confirm
      the immunochemistry study. Prognostic histologic markers such as cell typing,
      pigmentation, larger tumor dimension, mitotic figures, nucleolar size, scleral
      invasion, and optic nerve head invasion were reported. RESULTS: Nuclear
      positivity for p16 was observed in 11 tumors (34%) without any association with
      clinicopathologic parameters. Tumor cells positive for p21 were detected in 12
      choroidal melanomas (37%). Unexpectedly, a positive relationship was seen between
      p21 and scleral invasion (P: = 0.008). Nuclear positivity for p27 was observed in
      nine tumors (28%). An inverse correlation was observed between the number of
      mitotic figures and p27 immunoreactivity (P: = 0.03), as well as between Mib-1
      positivity and p27 expression (P: = 0.02). Western blot assays of tumor extracts
      confirmed overexpression of p21 and p27. CONCLUSIONS: The results suggest that
      p21 and p27 may be involved in tumorigenesis in choroidal melanoma.

PMID- 10967036
TI  - Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green
      stained leukocytes.
AB  - PURPOSE: To develop a new method with which to visualize leukocytes moving
      through the choroidal vessels of pigmented animals and enable the evaluation of
      leukocyte dynamics in the choroidal microcirculation. METHODS: Pigmented rabbits
      and monkeys were used in this study. Leukocytes, collected by centrifugal
      separation of autologous blood, were stained with indocyanine green (ICG) dye.
      The ICG-stained leukocyte fluid was injected into the vein, and the fundus image
      was obtained with a scanning laser ophthalmoscope. The image was recorded on
      videotapes and analyzed with a personal computer-based image analysis system.
      RESULTS: In pigmented rabbits, fluorescent leukocytes moving in the choroidal
      circulation were clearly visible for more than 1 hour. In monkeys, distinct
      fluorescent dots were seen moving approximately 50 to 200 microm in the foveal
      avascular zone for more than 30 minutes after the injection of the ICG-stained
      leukocyte fluid. Dim fluorescent dots were seen moving in the fundus. Although
      the movement of these dim dots was difficult to trace, they seemed to be moving
      in the choroidal vessels. In the rabbits, the mean flow velocity of leukocytes
      moving without plugging was 0.48 +/- 0.14 mm/sec in the peripheral
      choriocapillaris. In the monkeys, the mean flow velocity of distinct fluorescent
      leukocytes without plugging was 2.45 +/- 0. 48 mm/sec in the posterior choroid.
      CONCLUSIONS: In pigmented rabbits and monkeys, this method allows visualization
      of leukocytes passing through the choroidal vessels and provides a new way to
      investigate, noninvasively and in vivo, leukocyte dynamics in the choroidal
      microcirculation.

PMID- 10967037
TI  - Nuclear trafficking of photoreceptor protein crx: the targeting sequence and
      pathologic implications.
AB  - PURPOSE: To identify the targeting sequence controlling the nuclear transport of
      the photoreceptor-specific transcription factor cone-rod homeobox (Crx) protein
      and to address the question of whether disease-causing Crx mutations disrupt the
      nuclear trafficking of the Crx protein. METHODS: A series of cDNA fragments
      encoding Crx protein with deleted C termini were generated from mouse Crx cDNA by
      polymerase chain reaction (PCR). Point mutations were introduced into Crx coding
      sequence through PCR-based, site-directed mutagenesis. These mutated Crx
      fragments and the wild-type Crx were fused to cDNA encoding the jellyfish green
      fluorescent protein (GFP) and were transiently expressed in human embryonic
      kidney (HEK) 293T cells. Twelve to 48 hours after transfection, the living cells
      were counterstained with the red fluorescent nucleic acid dye SYTO 59 and
      examined with epifluorescence and confocal microscopy to determine the
      subcellular localization of Crx fusion proteins. RESULTS: GFP expressed without a
      fusion partner was distributed evenly throughout the cells, whereas the wild-type
      Crx protein fused to GFP was localized only in the nucleus. GFP-tagged Crx
      proteins truncated at residues 107 or 165, demonstrated exclusive nuclear
      localization. In contrast, Crx fusion proteins truncated at residues 88, 79, 44,
      and 36, were located equally in both the cytoplasm and the nucleus. These results
      demonstrate that the nuclear localization signal (NLS) of Crx appears to reside
      in the amino acids between residue 88 and 107, which is surprising because the
      putative NLSs identified by prosite search are at residues 36 to 43 and 116 to
      122. Further, a Crx fusion protein truncated at residue 99 was localized within
      the nucleus in the majority of the transfected cells, and two point mutations at
      residues 88 (K88T) and 98 (R98L) disrupted the nuclear localization, which
      indicates that the sequence between 88 and 98 in the C terminus of the Crx
      homeodomain contains a NLS that is essential for targeting Crx to the nucleus.
      However, the fusion protein truncated at residue 99 did not produce a complete
      nuclear localization in every transfected cell, suggesting that the Gln-rich
      domain at residues 99 to 106 is also required for the full accumulation of Crx
      protein in the nucleus. Two point mutations of Crx, R41W and E80A, that cause
      cone-rod dystrophy in humans and lie within the homeodomain but outside the NLS
      did not disrupt the nuclear localization of Crx protein, but a R90W mutation of
      Crx that causes human Leber congenital amaurosis (LCA) and resides within the NLS
      resulted in the fusion protein localized in both nuclei and cytoplasm in majority
      (51% to 69%) of the transfected cells. CONCLUSIONS: The wild-type Crx protein is
      localized within the nucleus. The putative NLSs of Crx at residues 36 to 43 and
      116 to 122 are not essential. The minimal NLS necessary for the nuclear transport
      of Crx protein is located at residues 88 to 98 in the C terminus of the
      homeodomain. The R90W mutation of Crx found in LCA disrupts the nuclear transport
      of the mutant protein. The defective nuclear trafficking of Crx protein may be a
      part of the molecular mechanism of this early-onset retinal degeneration.

PMID- 10967038
TI  - Heat shock cognate-70 gene expression declines during normal aging of the primate
      retina.
AB  - PURPOSE: Despite documented age-related changes in retinal function and
      histology, little is known about the pattern of gene expression during normal
      aging of the vertebrate retina. This study was undertaken to definitively
      characterize gene expression in the primate retina during aging. METHODS: Human
      retina cDNA library clones were arrayed at high density on nylon membranes and
      screened with mixed cDNA probes generated from young (4-year-old) and old (80
      year-old) human retinae. Clones showing a more than twofold difference in
      intensity were rescreened by dot blot analysis with the same probes and with
      mixed cDNA probes generated from young (2-3 years) and old (27-35 years) rhesus
      monkeys. One clone identified by its differential (age-putative) signal, and age
      related differential expression was used for analysis of Northern blot analysis
      of total retinal RNA from human donors (35 weeks to 94 years of age) and two
      rhesus monkeys (2 and 27 years of age). The identified clone was sequenced and
      compared with entries in the GenBank/EMBL databases. Western blot analysis was
      performed on protein isolated from the retina of human donors aged 4 to 64 years
      and rhesus monkeys aged 18 months and 35 years. RESULTS: Approximately 1.6% of
      the 55,368 retina-expressed sequences examined show age-related changes between
      tissues from young and old donors. The mRNA level one clone, identical with heat
      shock cognate (HSC)70, was altered during normal retinal aging in primates.
      Regression analysis of Northern blot analysis signals from 23 human donors
      suggested that there may be a two- to threefold decrease in HSC70 mRNA levels in
      the human retina by the eighth decade of life. Western blot analysis also showed
      lower levels of the 70-kDa HSC protein in older tissues of both primates.
      CONCLUSIONS: HSC70 mRNA levels apparently decline during normal aging of the
      primate retina. Because the heat shock 70 protein family may play important roles
      in ocular development and protection from various biologic and environmental
      stresses, decreased HSC70 levels in the retina during aging may contribute to the
      apparent increased susceptibility of the retina to age-acquired retinal disease.

PMID- 10967039
TI  - Ribozyme-based therapeutic approaches for autosomal dominant retinitis
      pigmentosa.
AB  - PURPOSE: To design, generate, and compare in vitro a range of hammerhead
      ribozymes targeting retinal transcripts implicated in autosomal dominant
      retinitis pigmentosa (adRP) and thereby identify ribozymes that may be valuable
      as therapeutic agents for adRP. To address mutational heterogeneity in rhodopsin
      and peripherin-linked adRP using mutation-independent ribozyme-based therapeutic
      approaches. METHODS: Ribozyme and cDNAs constructs were cloned into pcDNA3 and
      expressed in vitro from the T7 promoter. Cleavage reactions were separated on
      polyacrylamide gels, visualized by autoradiography, and quantified using an
      instant imager. Ribozymes targeting rhodopsin and peripherin transcripts in a
      mutation-independent manner (Rz9, Rz10, and Rz40) and a multimeric ribozyme
      (RzMM) targeting rhodopsin transcripts were evaluated for in vitro activity.
      Parameters such as V:(max), K:(m), k(2) and k(-1) were established for each
      ribozyme. RESULTS: Four ribozymes targeting retinal transcripts were evaluated.
      Mutation-independent ribozymes targeting degenerate sites or untranslated regions
      in retinal transcripts resulted in cleavage products of predicted size, whereas
      transcripts from modified replacement genes remained intact. Detailed kinetic
      evaluation of ribozymes revealed substantial differences in cleavage rates
      between ribozymes. CONCLUSIONS: Mutation-independent hammerhead ribozymes
      targeting rhodopsin and peripherin have been screened in vitro, and a number of
      extremely efficient ribozymes identified subsequent to detailed kinetic analyses,
      suggesting that these ribozymes may provide mutation-independent methods of
      treating adRP. These are the first ribozymes reported that potentially will
      provide benefit for inherited retinopathies.

PMID- 10967040
TI  - Component perimetry: a fast method to detect visual field defects caused by brain
      lesions.
AB  - PURPOSE: Noise field campimetry, performed according to Aulhorn and Kost,
      confronts patients with a large field of irregularly flickering dots, and many
      patients immediately perceive their visual field defects. The original method had
      a somewhat low specificity and sensitivity, especially for patients with visual
      field defects caused by cortical lesions. METHODS: The method was improved in two
      ways. First, the grain of the visual noise was increased toward the periphery of
      the visual field to accommodate the peripheral decrease in visual acuity. Second,
      the type of stimulus pattern was varied to include separate investigations of
      different visual components or functions (color, motion, temporal resolution,
      line orientation, stereoscopic depth, acuity, and figure-ground segmentation). To
      evaluate the reliability of the method, the visual fields were compared, as
      assessed by the new method, with those of conventional perimetry in 41 patients
      with neurologic disorders and 22 normal control subjects. RESULTS: The results
      were encouraging. All patients with suprageniculate lesions subjectively
      experienced visual field defects in component perimetry. Sizes of visual field
      defects obtained with both methods corresponded qualitatively with each other,
      with a highly significant correlation. The specificity of component perimetry was
      higher than that of the original noise field campimetry. CONCLUSIONS: This pilot
      study indicates that component perimetry is a subjective but relatively reliable
      method for detecting disorders of visual perception caused by lesions at
      different stages along the visual pathway, permitting fast screening of the
      visual field. In addition, this method seems to allow examination of the visual
      field, not only for defects in contrast sensitivity, as does conventional light
      perimetry, but also for the status of other components of vision such as color or
      motion perception. Further evaluation with larger patient cohorts is needed to
      allow exact assessment of the clinical usefulness of the method.

PMID- 10967041
TI  - Apoptosis in the endothelium of human corneas for transplantation.
AB  - PURPOSE: To determine whether endothelial cell loss of human corneas stored in
      organ culture before transplantation is due to apoptosis. METHODS: The corneal
      endothelium of human corneas, stored in organ culture at 34 degrees C for varying
      periods of time, were analyzed for the presence of apoptotic cells using the TdT
      mediated dUTP nick-end labeling (TUNEL) technique. Corneal endothelial cell
      apoptosis was confirmed by Hoechst staining and immunolabeling with anti-caspase
      3 active antibody. RESULTS: Apoptotic cells were identified in the corneal
      endothelium of human organ cultured corneas: their number and distribution
      demonstrated a close correlation with corneal folding and overall quality of the
      corneal endothelium. TUNEL-positive labeling of cells was confirmed as apoptotic
      by the presence of morphologic nuclear alterations identified by Hoechst staining
      and the presence of immunostaining for caspase-3 activity. Corneal endothelial
      cell apoptosis was independent of cause of donor death, death to enucleation
      time, and death to culture times. CONCLUSIONS: Corneal endothelial cell apoptosis
      appears to determine the suitability of a cornea for transplantation.

PMID- 10967042
TI  - Differential expression of MT1-MMP (MMP-14) and collagenase III (MMP-13) genes in
      normal and wounded rat corneas.
AB  - PURPOSE: Several members of the matrix metalloproteinase (MMP) group have been
      identified in the rat cornea during corneal wound healing. The aim of the present
      study was to identify additional members of the MMP gene family in the rat cornea
      and localize the expression of membrane type-1 matrix metalloproteinase (MT1-MMP;
      MMP-14) and collagenase III (MMP-13) in normal and wounded corneas. METHODS:
      Adult rats underwent laser keratectomy on the right eye. Unwounded left eyes were
      normal controls. Corneas were collected and processed at different times post
      wounding. Reverse transcription-polymerase chain reaction (RT-PCR) and DNA
      sequencing were used to discover the MMP genes expressed in the corneas. In situ
      hybridization was performed to localize the mRNA expression of MMP-14 and MMP-13.
      RESULTS: MMP-13 mRNA was detected in epithelial cells of wounded corneas, but not
      in normal controls; MMP-14 was found in both normal and wounded corneas. MMP-14
      mRNA was expressed predominantly in the stromal keratocytes and rarely in the
      basal epithelial cells in normal and wounded corneas. MMP-13 mRNA was localized
      exclusively to basal cells of the epithelium at the wounded area from 6 hours to
      3 days after wounding. CONCLUSIONS: MMP-14 and MMP-13 expression in rat corneas
      parallels that of gelatinases A and B, respectively. MMP-13 may play an important
      role in the gelatinase B-associated proteolytic cascade that allows rapid
      turnover of the extracellular matrix (ECM) components during corneal wound
      healing. MMP-14 may contribute to removing abnormal ECM components through
      activation of gelatinase A in rat corneas.

PMID- 10967043
TI  - Human uroplakin Ib in ocular surface epithelium.
AB  - PURPOSE: To investigate the expression and localization of the human gene
      encoding uroplakin Ib in ocular surface epithelium. METHODS: The full-length cDNA
      of human uroplakin Ib was isolated from a cDNA library of human corneal
      epithelium, and the expression of uroplakin Ib in various tissues was examined by
      reverse transcription-polymerase chain reaction (RT-PCR). In cornea and
      conjunctiva, the expressions of uroplakin Ia, II, and III were also examined by
      RT-PCR. Finally, the localization of uroplakin Ib in the ocular surface was
      analyzed by immunofluorescence confocal microscopy, by using an antiserum against
      a synthetic peptide. RESULTS: Two mRNA isoforms, arising through two
      polyadenylation sites, were isolated. RT-PCR detected uroplakin Ib in cornea,
      conjunctiva, bladder, placenta, and kidney. Among other uroplakins, uroplakin II
      was also faintly detected in cornea and conjunctiva. Immunofluorescence confocal
      microscopy documented uroplakin Ib protein in the cell membranes of superficial
      and wing cells in the corneal epithelium. It was not found, however, in the most
      apical corneal epithelial cells. In limbus and conjunctiva, uroplakin Ib was also
      localized in the cell membranes of all epithelial layers, apart from the most
      apical cells. CONCLUSIONS: Uroplakin Ib is highly expressed in ocular surface
      epithelia. As in bladder epithelium, uroplakin Ib may protect the ocular surface
      from bacterial infection.

PMID- 10967044
TI  - Modulation of acute inflammation and keratocyte death by suturing, blood, and
      amniotic membrane in PRK.
AB  - PURPOSE: To investigate the role of acute inflammation in keratocyte death, which
      may influence corneal haze after photorefractive keratectomy (PRK). METHODS:
      Transepithelial PRK was performed on both eyes of 30 rabbits. Twenty-six rabbits
      were divided into 4 groups receiving autologous blood, suturing alone, suturing
      with amniotic membrane graft, or no treatment as the control. Twenty-four hours
      later, the ablated zone was analyzed for keratocyte death by TdT-dUTP terminal
      nick-end label (TUNEL) staining and transmission electron microscopy, for
      polymorphonuclear cell (PMN) infiltration by hematoxylin-eosin staining, and for
      oxygen radical-induced lipid peroxidation by malondialdehyde
      immunohistochemistry. The remaining four rabbits were subjected to PRK or
      mechanical scraping and analyzed immediately or after culturing for 24 hours.
      RESULTS: Compared with the control group where TUNEL-positive keratocytes were
      found only in the superficial ablated stroma, blood application or suturing
      caused more and deeper keratocyte death and PMN infiltration (P: < 0.05). The
      amniotic membrane graft group had less keratocyte death and PMN than the control
      or the suture group (P: < 0.05 and P: < 0.01, respectively). There was a strong
      correlation between keratocyte death and PMN infiltration (P: < 0.01, correlation
      factor = 0.786). Transmission electron microscopy revealed that the majority of
      keratocyte death was due to necrosis. Amniotic membrane stroma trapped and
      prevented PMN infiltration into the stroma. Malondialdehyde-modified antigen was
      found on the ablated surface and around infiltrated PMN. CONCLUSIONS:
      Transepithelial PRK causes oxygen radical-mediated lipid peroxidation on the
      superficial stroma and may contribute to superficial keratocyte death even in the
      absence of inflammation. Mechanical scraping leads to apoptosis without the
      participation of inflammation. Keratocyte death by necrosis spreads to the deeper
      part of the stroma and correlates with additional acute inflammation. Amniotic
      membrane precludes PMN infiltration and decreases lipid peroxidation and
      keratocyte death. Future studies are needed to discern whether prevention of
      inflammation-mediated keratocyte necrosis can reduce unwanted scarring caused by
      PRK.

PMID- 10967045
TI  - Corneal structure and sensitivity in type 1 diabetes mellitus.
AB  - PURPOSE: Corneal wound healing is impaired in diabetic cornea. The purpose of
      this study was to examine patients with type 1 diabetes mellitus for changes in
      corneal morphology and to correlate corneal sensitivity, subbasal nerve
      morphology, and degree of polyneuropathy with each other. METHODS: Forty-four
      eyes of 23 patients with diabetes and nine control eyes were included. Corneal
      sensitivity was tested with a Cochet-Bonnet esthesiometer (Luneau, Paris,
      France), and corneal morphology and epithelial and corneal thickness were
      determined by in vivo confocal microscopy. The density of subbasal nerves was
      evaluated by calculating the number of long subbasal nerve fiber bundles per
      confocal microscopic field. The degree of polyneuropathy was evaluated using the
      clinical part of the Michigan Neuropathy Screening Instrument (MNSI)
      classification, and retinopathy was evaluated using fundus photographs. RESULTS:
      A reduction of long nerve fiber bundles per image was noted to have occurred
      already in patients with mild to moderate neuropathy, but corneal mechanical
      sensitivity was reduced only in patients with severe neuropathy. Compared with
      control subjects the corneal thickness was increased in patients with diabetes
      without neuropathy. The epithelium of patients with diabetes with severe
      neuropathy was significantly thinner than that of patients with diabetes without
      neuropathy. CONCLUSIONS: Confocal microscopy appears to allow early detection of
      beginning neuropathy, because decreases in nerve fiber bundle counts precede
      impairment of corneal sensitivity. Apparently, the cornea becomes thicker in a
      relatively early stage of diabetes but does not further change with the degree of
      neuropathy. A reduction in neurotrophic stimuli in severe neuropathy may induce a
      thin epithelium that may lead to recurrent erosions.

PMID- 10967046
TI  - Regulation of collagenase, stromelysin, and gelatinase B in human conjunctival
      and conjunctivochalasis fibroblasts by interleukin-1beta and tumor necrosis
      factor-alpha.
AB  - PURPOSE: Overexpression and increased activities of matrix metalloproteinases
      (MMPs) have recently been reported in cultured conjunctival fibroblasts from
      patients with conjunctivochalasis. The role of inflammatory cytokines in
      modulating expression of MMPs, their tissue inhibitors (TIMPs), and urokinase
      plasminogen activator (uPA) as potential contributors to the pathogenesis of
      conjunctivochalasis was investigated. METHODS: Interleukin-1beta (IL-1beta) or
      tumor necrosis factor-alpha (TNF-alpha) was added at 10 ng/ml to a serum-free
      medium. Expression of transcripts and proteins of MMPs, TIMPs, and uPA by
      cultured normal human conjunctival and conjunctivochalasis fibroblasts was
      determined by Northern hybridization, enzyme-linked immunosorbent assay (ELISA)
      and Western blot analysis, respectively. Gelatin and casein zymographies were
      performed in serum-free conditioned media with and without the respective enzyme
      inhibitors. RESULTS: Without challenging the cells, conjunctivochalasis
      fibroblasts showed mRNA and protein overexpression of MMP-1 and MMP-3 compared
      with normal conjunctival fibroblasts, which showed minor or no expression of
      these enzymes. IL-1beta markedly and TNF-alpha to lesser extent increased mRNA
      and protein expression of MMP-1 and MMP-3 in conjunctivochalasis fibroblasts from
      2 subjects when compared with normal conjunctival fibroblasts from 2 subjects and
      with their nonstimulated counterparts. In conjunctivochalasis fibroblasts and
      normal conjunctival fibroblasts, TNF-alpha, but not IL-1beta, induced a
      gelatinolytic activity of MMP-9, which was further confirmed by Western blot
      analysis and ELISA. Expression of MMP-2, TIMP-1, and TIMP-2 mRNA and protein was
      not influenced by IL-1beta or TNF-alpha, and no difference was found in the
      gelatinolytic activity of MMP-2 between both cell types. CONCLUSIONS:
      Inflammatory cytokines such as IL-1beta and TNF-alpha, which can potentially be
      derived from the ocular surface and tears, may be responsible for increased
      expression of MMPs in cultured conjunctivochalasis fibroblasts. Ocular
      inflammation might be one important denominator in the pathogenesis of
      conjunctivochalasis.

PMID- 10967047
TI  - EDTA: a promoter of proliferation in human corneal endothelium.
AB  - PURPOSE: To determine whether it is possible to induce proliferation in the
      endothelium of older donor corneas by treatment of the intact monolayer with
      EDTA. METHODS: Corneas from donors 52 to 75 years of age were obtained from an
      eye bank and were usually cut in quarters to increase sample size. The effect of
      EDTA dose (0.02-2.0 mg/ml) and incubation time (6, 30, and 60 minutes) on
      endothelial cell-cell contacts was evaluated by staining for ZO-1, a cell
      junction marker. Cell death was tested by a commercial live-dead assay. Corneal
      pieces were incubated for 0, 24, 48, or 60 hours in culture medium (M-199, 10%
      fetal bovine serum, 10 ng/ml epidermal growth factor, 20 ng/ml fibroblast growth
      factor) before EDTA treatment. After treatment, pieces were incubated in the same
      medium for 24, 48, 72, or 96 hours to permit cell cycle entry. Tissue was fixed,
      stained for Ki67 (a marker for late G1-phase through the M-phase), and mounted in
      medium containing propidium iodide to visualize all nuclei. Confocal images were
      evaluated by computer (Image software; NIH, Bethesda, MD) to count Ki67-positive
      and propidium iodide-stained cells. RESULTS: EDTA released corneal endothelial
      cell-cell contacts in a dose- and time-dependent manner. At doses and incubation
      times tested, EDTA did not induce significant cell death. Preincubation in
      culture medium for 24 hours was needed for endothelial cells to efficiently
      initiate proliferation in response to EDTA. The endothelium of corneas incubated
      in mitogen-containing medium for up to 108 hours without EDTA treatment did not
      stain for Ki67. EDTA at 2.0 mg/ml for 60 minutes appeared optimal and stimulated
      16% to 18% of the cells to proliferate. Ki67-positive mitotic figures were
      visible 48 hours after exposure to EDTA. Formation of daughter cells was visible
      after double-staining for Ki67 and ZO-1. CONCLUSIONS: EDTA released cells from
      contact inhibition and promoted proliferation in corneal endothelium from older
      donors. The authors hypothesize that corneal endothelium from older individuals
      divide in situ when exposed to positive growth factors under conditions in which
      cells have been transiently released from contact inhibition.

PMID- 10967049
TI  - On-line 3-dimensional confocal imaging in vivo.
AB  - PURPOSE: In vivo confocal microscopy through focusing (CMTF) can provide a 3-D
      stack of high-resolution corneal images and allows objective measurements of
      corneal sublayer thickness and backscattering. However, current systems require
      time-consuming off-line image processing and analysis on multiple software
      platforms. Furthermore, there is a trade off between the CMTF speed and
      measurement precision. The purpose of this study was to develop a novel on-line
      system for in vivo corneal imaging and analysis that overcomes these limitations.
      METHODS: A tandem scanning confocal microscope (TSCM) was used for corneal
      imaging. The TSCM video camera was interfaced directly to a PC image acquisition
      board to implement real-time digitization. Software was developed to allow in
      vivo 2-D imaging, CMTF image acquisition, interactive 3-D reconstruction, and
      analysis of CMTF data to be performed on line in a single user-friendly
      environment. A procedure was also incorporated to separate the odd/even video
      fields, thereby doubling the CMTF sampling rate and theoretically improving the
      precision of CMTF thickness measurements by a factor of two. RESULTS: In vivo
      corneal examinations of a normal human and a photorefractive keratectomy patient
      are presented to demonstrate the capabilities of the new system. Improvements in
      the convenience, speed, and functionality of in vivo CMTF image acquisition,
      display, and analysis are demonstrated. CONCLUSIONS: This is the first full
      featured software package designed for in vivo TSCM imaging of the cornea, which
      performs both 2-D and 3-D image acquisition, display, and processing as well as
      CMTF analysis. The use of a PC platform and incorporation of easy to use, on
      line, and interactive features should help to improve the clinical utility of
      this technology.

PMID- 10967048
TI  - Molecular cloning and expression of an inwardly rectifying K(+) channel from
      bovine corneal endothelial cells.
AB  - PURPOSE: To determine the presence of a putative inwardly rectifying K(+) channel
      in bovine corneal endothelial (BCE) cells and to characterize its molecular and
      electrophysiological properties. METHODS: An RT-PCR strategy was used to clone an
      IRK1 channel sequence from BCE mRNA. Northern blot analysis was used to confirm
      expression of this sequence in cultured BCE cells. Two-electrode voltage-clamp
      and whole-cell patch-clamp recordings were used to characterize the cloned
      channel expressed in Xenopus oocytes and the native channels in cultured BCE
      cells, respectively. RESULTS: A full-length (1284 bp) coding sequence that shares
      99.7% nucleotide sequence and 100% amino acid sequence identity to bovine lens
      IRK1 (Kir2.1) was cloned. The authors designate this sequence BCE IRK1 or BCIRK1.
      Northern blot analysis indicated that BCIRK1 mRNA is expressed in cultured BCE
      cells with two major transcripts of 7.5 and 5.5 kb. BCIRK1 cDNA was subcloned
      into the vector, pcDNA3.1(-), and cRNA transcribed from the BCIRK1 cDNA clone was
      injected into Xenopus oocytes. Two-electrode voltage-clamp recordings from
      injected oocytes revealed inwardly rectifying K(+) currents that were blocked by
      external Ba(2+) and Cs(+) in a concentration- and voltage-dependent manner. Whole
      cell patch-clamp recordings from dissociated cultured BCE cells revealed strongly
      inwardly rectifying K(+) currents with similar properties. CONCLUSIONS: Corneal
      endothelial cells express IRK1 (Kir2.1) inwardly rectifying K(+) channels.
      Consistent with the properties of IRK1 channels, BCIRK1 is likely involved in
      regulating membrane potential and possibly other cellular functions in corneal
      endothelial cells.

PMID- 10967050
TI  - Effects of a fixation target on torsional optokinetic nystagmus.
AB  - PURPOSE: To investigate the effects of an imaginary and a visual target on
      torsional optokinetic nystagmus (tOKN) and directional symmetry of tOKN. METHODS:
      Torsional OKN was induced by a rotating random dot pattern (52 degrees in
      diameter, constant angular velocity: +/-30 deg/sec to +/-52 deg/sec) with an
      imaginary or a visual target in 11 eyes of 10 healthy humans by dual-search coil
      methods. RESULTS: Intorsional OKN and extorsional OKN were symmetrical in their
      slow-phase gain. The mean slow-phase gain (0. 037/0.041, intorsion/extorsion) of
      tOKN during fixation on a visual target at the center of the rotating random dot
      pattern was significantly (P: < 0.002) smaller than that (0.051/0.052,
      intorsion/extorsion) during fixation on an imaginary target at the center of the
      rotating random dot pattern. The mean tOKN slow-phase beat duration (840 msec/724
      msec, intorsion/extorsion) during fixation on the visual target was significantly
      (P: < 0.002) longer than that (585 msec/543 msec, intorsion/extorsion) during
      fixation on the imaginary target. In seven eyes of six subjects, the mean slow
      phase gain and beat duration (0.034 and 812 msec) of tOKN during fixation on a
      visual target 6.5 degrees left or right from the center of the rotating random
      dot pattern were not significantly different from those (0.037 and 825 msec) with
      a visual target at the center of the rotating random dot pattern (P: > 0.3).
      CONCLUSIONS: A visual target spot suppresses tOKN by a nonpursuit visual system.
      Intorsional and extorsional OKNs were symmetrical.

PMID- 10967051
TI  - Ultrasonographic evaluation of optic disc swelling: comparison with CSLO in
      idiopathic intracranial hypertension.
AB  - PURPOSE: To determine the accuracy and reproducibility of ultrasonographic (US)
      readings of optic disc elevations in patients with papilledema compared with
      confocal scanning laser ophthalmoscope (CSLO) measurements. METHODS: One randomly
      selected eye of 22 patients with idiopathic intracranial hypertension (IIH) and a
      variable degree of optic disc swelling underwent five and three repeated
      measurements of disc height using high-resolution ultrasonography (Biovision
      unit; Quantel Medical, Clermont-Ferrand, France) and CSLO (Heidelberg Retina
      Tomograph [HRT]; Heidelberg Engineering, Heidelberg, Germany), respectively. The
      same procedure was assessed in 14 subjects with variable degrees of physiologic
      optic disc cupping. US and HRT measurements from each group were individually
      compared with each other to estimate the accuracy of US readings in both disc
      conditions in comparison with HRT data. RESULTS: Ultrasonographic readings were
      positively correlated with HRT measurements in both swollen (r = 0.62, P: =
      0.002) and excavated disc (r = 0.84, P: < 0.0002). The 95% limits of agreement
      between the instruments were 0.24 +/- 0.59 mm (mean +/- 2 SD) and 0. 05 +/- 0.3
      mm for swelling and cupping measurements, respectively. The coefficient of
      variation was 7.63% and 1.8% for swelling and 7. 93% and 5.91% for cupping, with
      US and HRT, respectively. CONCLUSIONS: The results indicate that US and CSLO
      readings are correlated i: both disc swelling and cupping conditions, but to a
      different extent because of a significant discrepancy in papilledema. US
      assessment can be considered highly reproducible. Combined US and HRT optic disc
      analysis may be recommended in papilledema evaluation as long as a better
      correlation can be demonstrated in further studies.

PMID- 10967052
TI  - The combined effect of brain-derived neurotrophic factor and a free radical
      scavenger in experimental glaucoma.
AB  - PURPOSE. Brain-derived neurotrophic factor (BDNF) had a limited effect on the
      survival of retinal ganglion cells (RGCs) in rats' eyes with elevated intraocular
      pressure (IOP). The combined treatment of BDNF and a nonspecific free radical
      scavenger N-tert-butyl-(2-sulfophenyal)-nitrone (S-PBN) was investigated on the
      RGCs in hypertensive eyes of rats. METHODS: Adult Wistar rats were separated into
      five groups: BDNF (0.5 microg) + S-PBN; BDNF (1. 0 microg) + S-PBN; BDNF (1.0
      microg); S-PBN; and phosphate-buffered saline. Right eyes served as normal
      controls (n = 10). RGCs were labeled with 5% Fluoro Gold; injected into the
      superior colliculus. Three days after intratectal injection, the episcleral veins
      of the left eyes were cauterized. Intravitreal injection of BDNF was performed on
      days 5, 13, 21, and 29 after IOP elevation. S-PBN was injected intraperitoneally
      (100 mg/kg body wt) every 12 hours starting 30 minutes after cauterization.
      RESULTS: The survival of RGCs using BDNF treatment alone in moderately
      hypertensive eyes and systemic administration of S-PBN alone did not
      significantly rescue the RGCs. However, the combination of BDNF and S-PBN
      increased the survival of RGCs to 90.1%. CONCLUSIONS: Trophic factors and
      antioxidants have synergistic effects on rescuing RGCs from death in eyes with
      elevated IOP. Further studies of different combined treatment therapies may
      provide avenues to save RGCs from death in eyes with elevated IOP.

PMID- 10967053
TI  - Influence of experimental chronic high-pressure glaucoma on age-related macular
      degeneration in rhesus monkeys.
AB  - PURPOSE: To assess prospectively whether development of age-related macular
      degeneration is influenced by experimentally induced chronic high-pressure
      glaucoma, and whether age-related macular degeneration influences the appearance
      of the optic nerve head in experimental chronic high-pressure glaucoma in older
      rhesus monkeys. METHODS: The longitudinal study included 102 eyes of 52 rhesus
      monkeys. The total study group was divided into a group with experimentally
      induced unilateral chronic high-pressure glaucoma (n = 40 eyes) and a normal
      control group (n = 62 eyes). Additionally, arterial hypertension and
      atherosclerosis were experimentally induced in both study groups in a similar
      percentage of monkeys. Mean monkey age at the end of the study was 19.6 +/- 3.1
      years (range, 13-24 years). The macular region, optic disc, and retinal nerve
      fiber layer were morphometrically evaluated by color wide-angle fundus
      photographs taken at baseline and at the end of the study. RESULTS: The degree of
      age-related macular degeneration, measured as number and area of drusen in the
      foveal and extrafoveal region of the macula, did not differ significantly between
      the two study groups. In the glaucomatous group, the degree of macular
      degeneration was statistically independent of the development of parapapillary
      atrophy, loss of neuroretinal rim, and decrease in the visibility of the retinal
      nerve fiber layer. CONCLUSIONS: Development of age-related macular degeneration
      in rhesus monkeys is independent of concomitant chronic high-pressure glaucoma,
      including the development of glaucomatous parapapillary chorioretinal atrophy.
      Conversely, age-related macular degeneration does not markedly influence the
      course of experimental chronic high-pressure glaucoma or the development of
      parapapillary atrophy in monkeys.

PMID- 10967054
TI  - Ophthalmoscopic appearance of the normal optic nerve head in rhesus monkeys.
AB  - PURPOSE: To evaluate the ophthalmoscopic appearance of the normal optic disc,
      parapapillary region, and retinal nerve fiber layer in rhesus monkeys. METHODS:
      Color stereo fundus photographs of 17 normal eyes of 17 rhesus monkeys aged
      between 13 and 23 years were morphometrically evaluated. RESULTS: The
      neuroretinal rim was significantly (P: < 0.008) broadest in the inferior disc
      region followed by the superior disc region, the nasal region, and the temporal
      region. Retinal nerve fiber layer visibility was significantly highest in the
      inferior temporal fundus region followed by the superior temporal fundus region,
      the superior nasal fundus region, and the inferior nasal fundus region. It
      decreased significantly (P: < 0.001) with increasing age. The retinal arterioles
      were significantly (P: < 0.01) wider in the inferior temporal and superior
      temporal fundus regions than in the superior nasal and inferior nasal fundus
      regions. The alpha zone of parapapillary atrophy (14/17 or 82.4%) occurred
      significantly (P: < 0.001) more often than the beta zone (2/17 or 11.8%). In 15
      eyes (88. 2%), the foveola was located inferior to a horizontal line drawn
      through the center of the optic disc. Neuroretinal rim shape and area and size of
      alpha and beta zones of parapapillary atrophy were independent of age.
      CONCLUSIONS: As in humans, in normal rhesus monkeys the neuroretinal rim has a
      typical physiologic configuration that spatially correlates with the retinal
      arteriole diameter, retinal nerve fiber layer visibility, and position of the
      foveola inferior to the center of the optic disc. Neuroretinal rim shape is
      independent of age. Retinal nerve fiber layer visibility decreases significantly
      with increasing age. These findings may be useful for the early detection and
      differentiation of experimental optic nerve damage in rhesus monkeys.

PMID- 10967055
TI  - Giant vacuoles are found preferentially near collector channels.
AB  - PURPOSE: To determine whether giant vacuoles form preferentially near collector
      channels or over regions of optically empty space within the juxtacanalicular
      tissue (JCT). METHODS: To assess the relationship between giant vacuoles and
      collector channels, six eyes were perfused with phosphate-buffered saline (PBS)
      at 20 mm Hg and then fixed by perfusion. Serial sections were cut in the frontal
      plane and light microscopy used to count the number of giant vacuoles per length
      of Schlemm's canal. The number of giant vacuoles between two adjacent collector
      channels was determined. To assess the relationship between giant vacuoles and
      the ultrastructure of the JCT, an additional seven eyes were perfused with PBS at
      10 mm Hg, fixed by perfusion, and examined by transmission electron microscopy.
      The ultrastructural components of the JCT were quantitated with an image analysis
      system. RESULTS: Twice as many giant vacuoles were present in regions underlying
      collector channels as in regions between channels (giant vacuoles per histologic
      section: 14.0 +/- 1.7 versus 7.3 +/- 0.8, P: = 0.01). Giant vacuoles occurred on
      both the inner and outer walls of the canal but were more numerous on the inner
      wall (9.1 +/- 1.0 versus 2.6 +/- 0.4, P: < 0.001). No significant increase in
      optically empty space was found in the JCT regions underlying giant vacuoles
      compared with regions with no vacuoles (50.7% +/- 2.3% versus 47.3% +/- 2.5%, P:
      = 0.09). Examination of the amount of optically empty space immediately adjacent
      (within 1 microm) to the inner wall endothelial cells of the canal did not reveal
      a significant difference between regions under vacuoles and regions without giant
      vacuoles. CONCLUSIONS: Giant vacuoles are found preferentially near collector
      channels, indicating that aqueous flow across the inner wall is sensitive to
      downstream pressure. The variability in giant vacuole distribution noted in
      previous studies is in part due to the distance of the vacuoles from the
      collector channels. No distinct findings in the JCT were associated with the
      presence of giant vacuoles.

PMID- 10967056
TI  - The optic nerve head as a biomechanical structure: initial finite element
      modeling.
AB  - PURPOSE: To study the relationship between intraocular pressure (IOP) and the IOP
      related stress (force/cross-sectional area) it generates within the load-bearing
      connective tissues of the optic nerve head. METHODS: Thirteen digital, three
      dimensional geometries were created representing the posterior scleral shell of
      13 idealized human eyes. Each three-dimensional geometry was then discretized
      into a finite element model consisting of 900 constituent finite elements. In
      five models, the scleral canal was circular (diameters of 0.50, 1.50, 1.75, 2.00,
      and 2.56 mm), with scleral wall thickness (0.8 mm) and inner radius (12.0 mm)
      held constant. In three models, the canal was elliptical (vertical-to-horizontal
      ratios of 2:1 [2.50 x 1.25 mm], 1.5:1 [2.1 x 1.4 mm], and 1.15:1 [1.92 x 1.67
      mm]), with the same constant scleral wall thickness and inner radius. In five
      additional models, scleral canal size was held constant (1.92 x 1.67 mm), and
      either scleral wall thickness (three models, 0.5, 1.0, and 1.5 mm) or inner
      radius (two models, 13.0 and 14.0 mm) was varied. In all models, each finite
      element was assigned a single isotropic material property, either scleral
      (modulus of elasticity, 5500 kPa) or axonal (modulus of elasticity, 55 kPa).
      Maximum stresses within specific regions were calculated at an IOP of 15 mm Hg
      (2000 Pa). RESULTS: Larger scleral canal diameter, elongation of the canal, and
      thinning of the sclera increased IOP-related stress for a given level of IOP. For
      all models, maximum IOP-related stress ranged from 6 x IOP (posterior sclera) to
      122 x IOP (laminar trabeculae). For each model, maximum IOP-related stress was
      highest within the laminar trabecular region and decreased progressively through
      the laminar insertion, peripapillary scleral, and posterior scleral regions.
      Varying the inner radius had little effect on the maximum IOP-related stress
      within the scleral canal. CONCLUSIONS: Initial finite element models show that
      IOP-related stress within the load-bearing connective tissues of the optic nerve
      head is substantial even at low levels of IOP. Although the data suggest that
      scleral canal size and shape and scleral thickness are principal determinants of
      the magnitude of IOP-related stress within the optic nerve head, models that
      incorporate physiologic scleral canal and laminar geometries, a more refined
      finite element model meshwork, and nonisotropic material properties will be
      required to confirm these results.

PMID- 10967057
TI  - Analysis of the cellular infiltrate in the iris during experimental autoimmune
      encephalomyelitis.
AB  - PURPOSE: Previous studies have shown that experimental autoimmune
      encephalomyelitis (EAE) and anterior uveitis (AU) develop in Lewis rats immunized
      with myelin basic protein (MBP). The purpose of this study was to characterize
      the dynamics, distribution, and phenotype of infiltrating cells in the iris
      during EAE-associated AU. METHODS: Lewis rats were immunized with MBP emulsified
      in complete Freund's adjuvant (CFA) or with CFA alone. Cellular infiltration of
      the iris was analyzed at various time points by immunohistochemistry of
      wholemounts, flow cytometry, and immunoelectron microscopy, by using monoclonal
      antibodies specific for monocytes/macrophages (ED1), T lymphocytes (R73, W3.25,
      OX8), T-cell activation markers (OX39, OX40), granulocytes (HIS48), major
      histocompatibility complex (MHC) class II (OX6), and neurofilament (2H3).
      RESULTS: MBP-immunized rats showed development of characteristic monophasic EAE,
      followed, after resolution of paralysis, by mild self-limited AU. Initially,
      focal infiltrates of round MHC class II(+) and ED1(+) cells were found in the
      iris. During the course of AU, the midiris became massively infiltrated with
      ED1(+) monocytes-macrophages, R73(+) T cells, granulocytes (HIS48(+)), and MHC
      class II(+) cells. The influx of T cells consisted of CD4(+) and CD8(+) cells, of
      which only a small fraction (<14 and 11%, respectively) expressed activation
      markers. The infiltrating cells accumulated in proximity to myelinated and
      nonmyelinated nerve bundles and in the vicinity of blood vessels in the iris. No
      evidence was found for demyelination or nerve degradation. Neither EAE nor AU
      developed in CFA-treated control rats. CONCLUSIONS: These data show that EAE
      associated AU is characterized by a transient mixed cellular infiltrate
      consisting of monocytes-macrophages, granulocytes, and CD4 and CD8 T cells. The
      preferential accumulation of inflammatory cells in the vicinity of nerve fibers
      suggests that AU in this model may result from autoreactivity to nerve antigens.

PMID- 10967058
TI  - The role of apoptosis within the retina of coronavirus-infected mice.
AB  - PURPOSE: To evaluate the possible roles of apoptosis in the murine retinopathy
      induced by coronavirus. METHODS: Mice were inoculated with virus intravitreally.
      Mouse eyes harvested at varying times after inoculation were evaluated for
      apoptotic and immunologic events by hematoxylin and eosin staining,
      immunohistochemical staining, in situ terminal deoxynucleotidyltransferase dUTP
      nick-end labeling (TUNEL) assay, and electron microscopy. Isolated retinas were
      analyzed for infectious virus and for expression of apoptosis-associated genes.
      RESULTS: The number of apoptotic events was significantly elevated in infected
      eyes from BALB/c and CD-1 mouse strains, reaching a maximum at days 6 through 10,
      and returning to normal levels at day 20. The majority of apoptotic cells were
      observed in the outer nuclear layer of the infected retina. In contrast, few
      apoptotic cells were observed in normal or mock-injected mouse eyes. Apoptotic
      events within the retina were associated with the presence of viral antigen,
      infiltration of CD8(+) T cells, and clearance of infectious virus. Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis identified the
      upregulation of Fas ligand (FasL) and granzyme B mRNAs within the infected
      retinas. The development of apoptosis, regulative gene expression, and viral
      clearance were similar in both retinal degeneration-susceptible (BALB/c) and 
      resistant (CD-1) mice. CONCLUSIONS: Retinal apoptosis was associated with retinal
      inflammation, a decrease in infectious virus, and upregulation of genes
      associated with CTL killing. These studies indicate that retinal apoptosis may be
      one of the host mechanisms that contribute to limiting this retinal infection.

PMID- 10967059
TI  - Aging and PMN response to P. aeruginosa infection.
AB  - PURPOSE: Alterations in immune system function associated with aging may
      contribute to increased morbidity in this population of individuals. The current
      studies were performed to determine aging-related changes in polymorphonuclear
      neutrophil (PMN) function after corneal infection with Pseudomonas aeruginosa.
      METHODS: Total PMN number, macrophage inflammatory protein (MIP)-2 mRNA and
      protein expression, and ocular bacterial load were determined in 8-week- and 12
      month-old inbred BALB/c mice at various times after infection with P. aeruginosa.
      In addition, 12-month-old mice were treated systemically with the MIP-2
      polyclonal antibody (pAb) to determine the effects of MIP-2 neutralization on
      ocular disease and PMN recruitment. RESULTS: Histologically, PMN infiltration
      into the cornea of 12-month-old mice was delayed initially and was associated
      with an inability to reduce bacterial load at later postinfection (PI) times. In
      addition, a significantly greater number of PMNs were found in the cornea of 12
      month-old mice at later PI times. The increase in PMN number in 12-month-old mice
      correlated with a persistence of MIP-2 expression in cornea at these later times.
      Systemic treatment of 12-month-old mice with neutralizing MIP-2 pAb versus normal
      rabbit serum (NRS) resulted in reduced corneal PMN number and ocular disease.
      CONCLUSIONS: These data provide evidence that persistence of PMN in the cornea of
      12-month-old mice contributes to corneal tissue destruction after P. aeruginosa
      challenge. Further evidence also is provided that the chemoattractant MIP-2
      contributes to the altered PMN response in these animals.

PMID- 10967060
TI  - Expression of human beta-defensins in intraocular tissues.
AB  - PURPOSE: Defensins are naturally occurring antimicrobial peptides. Recently the
      authors published evidence of defensin production by the human ocular surface. A
      study was undertaken to look for intraocular defensins that may account for
      unexplained antimicrobial activity of intraocular fluids. METHODS: Reverse
      transcription-polymerase chain reaction (RT-PCR) was performed on human
      postmortem ciliary body samples for beta defensins-1 (HBD-1) and beta defensin-2
      (HBD-2), and alpha defensins 5 and 6. Induction of defensins by cytokines was
      analyzed in cultured human ciliary body epithelial (CBE) and retinal pigment
      epithelial (RPE) cells. Polyclonal antibodies were used to immunoblot aqueous and
      vitreous to detect HBD-1 and HBD-2 and to estimate their concentration. RESULTS:
      RT-PCR revealed constitutive HBD-1 message in ciliary body. HBD-2 and alpha
      defensin 5 and 6 messages were absent. HBD-2 message was induced by cytokine
      stimulation of both CBE and RPE cells. Immunoblots of vitreous and aqueous
      stained positively for HBD-1 but not HBD-2. The estimated aqueous concentration
      of HBD-1 was less than 16 ng/ml. CONCLUSIONS: This study demonstrates that HBD-1
      is constitutively present in the aqueous and vitreous, probably at sub
      bacteriocidal concentrations. HBD-2 was absent from aqueous, but cytokine
      stimulation studies suggest that it may be generated in response to inflammatory
      cytokines during infections. HBD-2 has a wider antibacterial spectrum, is 10-fold
      more potent, and may play a more significant role in antimicrobial defense than
      HBD-1. The use of defensins therapeutically may be indicated; however, caution is
      required because defensins also promote cell proliferation and fibrin formation,
      which are 2 key elements in ocular scarring processes such as proliferative
      vitreoretinopathy.

PMID- 10967061
TI  - Immune privilege and immunogenicity reside among different layers of the mouse
      cornea.
AB  - PURPOSE: To determine the extent to which each layer of the mouse cornea displays
      alloimmunogenicity or immune privilege. METHODS: Intact corneas or individual or
      combined layers of corneas from normal or cauterized eyes of BALB/c, C57BL/6, and
      CD95L-deficient B6-gld mice were grafted beneath the kidney capsule of normal
      BALB/c, B10.D2, BALB.B mice or of BALB/c mice presensitized to donor antigens.
      Graft fate was assessed clinically and histologically and acquisition of donor
      specific delayed hypersensitivity (DH) was assessed at selected intervals after
      grafting. RESULTS: Full-thickness allogeneic corneas induced vigorous DH and were
      rejected acutely. Similar results were obtained with allografts of corneal
      epithelium alone (if supported by syngeneic viable stroma), allografts of
      epithelium from cauterized corneas (containing Langerhans' cells), and stromal
      allografts deprived of endothelium. Grafts comprised of stroma plus endothelium
      (without epithelium) were not rejected, nor did they induce DH unless the graft
      had no CD95L expression. If stroma-endothelium grafts had no CD95L expression, DH
      directed against major histocompatibility complex (MHC), but not minor
      histocompatibility, alloantigens was induced. Moreover, CD95L expressed on stroma
      endothelium grafts protected endothelial cells, but not stromal cells, from
      rejection in presensitized recipients. CONCLUSIONS: When grafted to a heterotopic
      site, the alloimmunogenicity of the normal cornea resides within its epithelial
      and stromal layers, whereas immune privilege arises from the endothelium. In
      normal mice, CD95L-expressing endothelium can inhibit the stroma from inducing
      immunity directed at MHC alloantigens, but in presensitized mice the endothelium
      can protect itself only from immune rejection.

PMID- 10967062
TI  - Optimal methods for preparation and immunostaining of iris, ciliary body, and
      choroidal wholemounts.
AB  - PURPOSE: Investigations into the biology of resident and infiltrating immune
      cells in the uveal tract of the rodent eye have been greatly aided by the use of
      tissue wholemount methods. These methods offer a number of advantages over
      conventional histological and frozen section techniques. The purpose of this
      article is to provide a detailed step by step guide to aid others who may wish to
      use this method. METHODS: A detailed description of whole-body perfusion
      fixation, dissection and isolation of the iris-ciliary body from the anterior
      segment and the choroid from the posterior segment is provided. In addition, the
      techniques used to handle whole tissue pieces during single and double
      immunohistochemical staining protocols, as well as the staining protocols
      themselves, are described. RESULTS: In refining the techniques described, the
      author has catalogued a number of frequent problems which compromise
      immunohistochemical staining results. A troubleshooting guide aimed to help
      identify the cause of common problems and with some suggested remedies is
      provided. CONCLUSIONS: Although tissue wholemounts are frequently used in retinal
      research, a similar approach to investigating the components of the uveal tract
      has only recently been applied. The methods described in this article will
      provide sufficient detail for other investigators to obtain maximum benefit from
      this alternative approach and provide an additional technique to assist in their
      investigations of ocular immunobiology.

PMID- 10967063
TI  - Blocking chloride channels in the rat lens: localized changes in tissue hydration
      support the existence of a circulating chloride flux.
AB  - PURPOSE: To investigate the effects of inhibitors of chloride channels on lens
      volume and tissue architecture under isotonic conditions. METHODS: Rat lenses
      were maintained in organ culture under isotonic conditions in the presence of
      various putative chloride channel inhibitors. The effect of an inhibitor on lens
      wet mass and tissue morphology was determined by weighing and histologic
      examination, respectively. RESULTS: Exposure to 100 microM of either 5-nitro-2-
      (3-phenylpropylamino) benzoic acid (NPPB) or 4, 4'-diisothiocyanatostilbene-2,2'
      disulfonic acid (DIDS) caused an increase in wet mass and severe tissue
      disruption in the lens equatorial region. Two distinctly different zones of
      tissue damage were evident: a peripheral zone of fiber cell swelling and an inner
      zone of extensive tissue breakdown. Extracellular space dilations caused the
      extensive tissue damage in the inner zone and preceded the peripheral fiber cell
      swellings. That the observed effects were a consequence of the inhibition of
      chloride channels was supported by (1) the effectiveness of NPPB at the lower
      dose of 10 microM, (2) the absence of any NPPB effect in chloride-free medium,
      and (3) an identical effect after exposure to tamoxifen, an inhibitor of the
      chloride channel regulator p-glycoprotein. CONCLUSIONS: Study results indicate
      that chloride channels are active in the lens under isotonic conditions. The
      spatial and temporal pattern of morphologic changes that was observed is
      consistent with a steady state efflux of chloride ions and water from peripheral
      fiber cells and a corresponding influx into fiber cells deeper in the lens. These
      observations may therefore represent the first visualization of the chloride flux
      postulated by others to be a component of the lens internal circulation system.

PMID- 10967064
TI  - Expression of betaB(2)-crystallin mRNA and protein in retina, brain, and testis.
AB  - PURPOSE: To evaluate the expression of betaB(2)-crystallin mRNA and protein in
      rat, bovine, and human nonlens and nonocular tissues. METHODS: betaB(2)
      crystallin mRNA levels were detected by RT-PCR. betaB(2)-crystallin protein was
      purified from rat and bovine tissues by FPLC chromatography. FPLC fractions were
      analyzed by immunoblotting. The identity of betaB(2)-crystallin protein, isolated
      from the retina, was confirmed by protein microsequencing. RESULTS: betaB(2)
      crystallin transcript was detected in rat brain, rat testis, and human retina by
      RT-PCR. betaB(2)-crystallin transcript was not found in rat lung, heart, ovary,
      spleen, thymus, kidney, and liver or in human brain and testis. betaB(2)
      crystallin protein was partially purified from and its identity confirmed in rat
      brain, rat testis, and bovine retina. The bovine retinal protein was further
      confirmed to be authentic betaB(2)-crystallin by protein microsequencing.
      CONCLUSIONS: These results establish that betaB(2)-crystallin mRNA and protein
      are expressed in tissues outside of the lens and outside of the eye including
      retina, brain, and testis. Extralenticular and extraocular expression of betaB(2)
      crystallin, coupled with its participation in phosphorylation pathways, suggests
      that it has nonrefractive functions in these tissues.

PMID- 10967065
TI  - Impact of aging and hyperbaric oxygen in vivo on guinea pig lens lipids and
      nuclear light scatter.
AB  - PURPOSE: To measure lipid compositional and structural changes in lenses as a
      result of hyperbaric oxygen (HBO) treatment in vivo. HBO treatment in vivo has
      been shown to produce increased lens nuclear light scattering. METHODS: Guinea
      pigs, approximately 650 days old at death, were given 30 and 50 HBO treatments
      over 10- and 17-week periods, respectively, and the lenses were sectioned into
      equatorial, cortical, and nuclear regions. Lipid oxidation, composition, and
      structure were measured using infrared spectroscopy. Phospholipid composition was
      measured using (31)P-NMR spectroscopy. Data were compared with those obtained
      from lenses of 29- and 644-day-old untreated guinea pigs. RESULTS: The percentage
      of sphingolipid approximately doubled with increasing age (29-544 days old).
      Concomitant with an increase in sphingolipid was an increase in hydrocarbon chain
      saturation. The extent of normal lens lipid hydrocarbon chain order increased
      with age from the equatorial and cortical regions to the nucleus. These order
      data support the hypothesis that the degree of lipid hydrocarbon order is
      determined by the amount of lipid saturation, as regulated by the content of
      saturated sphingolipid. Products of lipid oxidation (including lipid hydroxyl,
      hydroperoxyl, and aldehydes) and lipid disorder increased only in the nuclear
      region of lenses after 30 HBO treatments, compared with control lenses. Enhanced
      oxidation correlated with the observed loss of transparency in the central
      region. HBO treatment in vivo appeared to accelerate age-related changes in lens
      lipid oxidation, particularly in the nucleus, which possesses less antioxidant
      capability. CONCLUSIONS: Oxidation could account for the lipid compositional
      changes that are observed to occur in the lens with age and cataract. Increased
      lipid oxidation and hydrocarbon chain disorder correlate with increased lens
      nuclear opacity in the in vivo HBO model.

PMID- 10967066
TI  - Retroillumination versus reflected-light images in the photographic assessment of
      posterior capsule opacification.
AB  - PURPOSE: To investigate the relative merit of retroillumination and of reflected
      light slit-lamp-derived photographs in the assessment of the opacification of the
      posterior lens capsule. METHODS: Retroillumination and slit-lamp-derived
      reflected-light photographs were taken on 23 consecutive eyes with posterior
      capsule opacification (PCO) in uncomplicated pseudophakia. Subjective grading was
      performed on both types of photographs to evaluate the extent and density of
      posterior capsular opacification. Best-corrected visual acuity (BCVA) before and
      after YAG laser capsulotomy was used to assess the impact of capsular
      opacification on visual function. RESULTS: After capsulotomy all patients
      attained a BCVA > or = 46 letters (> or =20/32) with a mean increase of 25
      letters, indicating that PCO was the cause of visual impairment in these
      patients. The relative capacity of retroillumination and of reflected-light
      photographs to adequately capture the extent and the severity of posterior
      capsule opacification varied considerably. Reflected-light images, in addition to
      frequently producing higher severity scores for the opacity than
      retroillumination photographs, in 4 of 23 eyes (17.4%) proved to be the only
      technique able to document the presence of PCO. CONCLUSIONS: Our results indicate
      that, with respect to retroillumination images, reflected-light photography has
      an increased ability to adequately capture the presence and the severity of PCO
      and that the use of only retroillumination images may lead to its
      underestimation. This may be relevant to clinical studies aiming to evaluate
      incidence and progression of this condition.

PMID- 10967067
TI  - Effects of systemic NO synthase inhibition on choroidal and optic nerve head
      blood flow in healthy subjects.
AB  - PURPOSE: There is evidence from animal studies that nitric oxide (NO) is a major
      determinant of ocular blood flow. In humans NO synthase inhibition reduces
      pulsatile choroidal blood flow, but no data on optic nerve head (ONH) vasculature
      are available yet. The goal of this study was to investigate the effects of NO
      synthase inhibition on human choroidal and ONH blood flow using laser Doppler
      flowmetry. METHODS: The study design was a randomized, placebo-controlled, double
      masked, balanced three-way crossover. On separate study days 12 healthy male
      subjects received infusions of N:(G)-nitro-L-arginine (L-NMMA; either 3 mg/kg
      over 5 minutes followed by 30 microg/kg per minute over 55 minutes or 6 mg/kg
      over 5 minutes followed by 60 microg/kg per minute over 55 minutes) or placebo.
      The effects of L-NMMA or placebo on choroidal and ONH blood flow were measured
      with laser Doppler flowmetry. In addition, laser interferometric measurement of
      fundus pulsation was performed in the macula to assess pulsatile choroidal blood
      flow. RESULTS: L-NMMA reduced all outcome parameters in the choroid and the ONH.
      The higher dose of L-NMMA caused a significant decrease in blood flow in the
      choroid (-26% +/- 9%; P: < 0.001) and the ONH (-20% +/- 16%; P: < 0.001) as
      evidenced from laser Doppler flowmetry and a significant decrease in fundus
      pulsation amplitude (-26% +/- 5%; P: < 0.001). CONCLUSIONS: These results
      indicate that NO is continuously released in human choroidal and ONH vessels.

PMID- 10967068
TI  - Active scatter factor (HGF/SF) in proliferative vitreoretinal disease.
AB  - PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) possesses mitogenic,
      motogenic, and morphogenic properties and has recently been implicated in various
      retinal diseases. The role of HGF/SF in proliferative vitreoretinal disease was
      investigated. METHODS: Sections of epiretinal membranes were stained
      immunohistochemically for cytokeratins, to identify HRPE cells, and for HGF/SF
      receptor (c-Met). Cultured HRPE cells were stained for c-Met and investigated for
      shape change in response to HGF/SF, by using image analysis. The dose-response
      relationship for HRPE cells to HGF/SF was investigated by a cell migration assay
      and the specificity of this response evaluated by a neutralization experiment.
      Subretinal fluid (SRF) and vitreous from patients with retinal detachment and
      proliferative vitreoretinopathy (PVR) plus vitreous from eyes obtained after
      death, eyes with macular hole, and eyes with proliferative diabetic retinopathy
      (PDR) were investigated for the presence of HGF/SF using an enzyme-linked
      immunosorbent assay (ELISA). HGF/SF activity was measured using an MDCK cell
      scatter assay. RESULTS: HRPE cells in epiretinal membranes and in culture
      expressed c-Met. Cultured HRPE cells responded to HGF/SF by an epithelial-to
      mesenchymal shape change and by cell migration, a response that increased with
      increasing concentrations of HGF/SF. This response was reduced in the presence of
      neutralizing antibody. There was evidence of HGF/SF in increasing concentrations
      in more severe PVR and in PDR when measured by ELISA, and, conversely, there was
      evidence of correspondingly decreasing HGF/SF activity when measured by MDCK cell
      scatter assay in these diseases. CONCLUSIONS: HGF/SF is present in normal and
      pathologic vitreous. HRPE cells respond by shape change and cell migration to
      HGF/SF. Concentrations of HGF/SF increase in proliferative vitreoretinal disease
      and increase in turn with increased severity of the disease, but HGF/SF
      bioactivity decreases (consistent with activator depletion). These findings are
      consistent with the hypothesis that HGF/SF may play a role in the HRPE
      mesenchymal transformation that typifies PVR.

PMID- 10967069
TI  - Dexamethasone and critical effect of timing on retinopathy.
AB  - PURPOSE: Administration of corticosteroids soon after birth has been reported to
      have deleterious, protective, and no effect on retinopathy of prematurity.
      Conflicting results may be due to timing of corticosteroid administration. The
      goal of this study was to determine effects of pretreatment and late
      dexamethasone on retinopathy in a mouse model. METHODS: The C57BL6 mouse model of
      oxygen-induced retinopathy (by placing animals in 75% oxygen from postnatal days
      7 through 12) was used to create retinal neovascularization. Dexamethasone at 0.5
      mg/kg per day was administered from day 1 through day 5 in the pretreatment
      group. The late-treatment group received 5 days of dexamethasone at the same dose
      beginning on day 12. Mice were killed at days 17 through 20, and retinal
      vasculature was assessed by a retinal scoring system of wholemount preparation
      after high-molecular-weight fluorescein-labeled dextran perfusion. In addition,
      retinal neovascularization was assessed by quantification of extraretinal
      neovascular nuclei in retinal sections. Statistical significance was defined as
      P: < 0.05 and was determined by the Kruskal-Wallis test, Mann-Whitney test, and
      Student's t-test. RESULTS: Oxygen-exposed animals that received treatment with
      dexamethasone before oxygen exposure had an improvement in retinopathy, with a
      median score of 6 (5,7; 25th,75th quartiles) compared with 10 (8,11) in the
      untreated oxygen-exposed (P: < 0.05). The group treated late (after oxygen
      exposure) with dexamethasone had a median score of 10 (9,11). Pretreatment
      reduced extraretinal vascularization, when assessed by quantification of
      neovascular nuclei, to a mean +/- SEM of 19 +/- 9, significantly less than in the
      untreated oxygen-exposed group (55 +/- 12; P: < 0.05). No difference was observed
      in the late-treatment group when compared with the untreated oxygen-exposed
      group. Significant growth retardation, indicated by body weight, was observed in
      the pretreatment (P: < 0.01) and late-treatment (P: < 0. 05) groups when compared
      with the control group. CONCLUSIONS: Timing of dexamethasone administration was
      critical to the inhibition of development of retinopathy in the mouse model.
      Degree of growth retardation, measured by body weight, also appeared to be time
      dependent. These data may explain the different results of clinical observations
      with respect to corticosteroid treatment, timing, and development of retinopathy.

PMID- 10967070
TI  - Human neural retinal transplantation.
AB  - PURPOSE: A pilot study of human neural retinal transplantation was undertaken to
      investigate three major issues: whether a safe surgical procedure could be
      devised for transplantation of neural retinal tissue into the subretinal space,
      whether the transplant would be accepted in the subretinal space, and whether an
      improvement in vision could be achieved. METHODS: Eight patients with bare light
      perception (LP) vision due to retinitis pigmentosa (RP) and one patient with bare
      LP vision due to advanced neovascular age-related macular degeneration (AMD)
      received subretinal transplants of human fetal retinal microaggregate suspensions
      without postoperative systemic immunosuppression. The patient with AMD also
      received a fetal retinal sheet transplant. The ages of the patients ranged from
      31 to 94 years (median, 55 years). The pre- and postoperative evaluations
      included visual function testing, detailed fundus examinations, fundus
      photography, fluorescein angiography, macular perimetry using a scanning laser
      ophthalmoscope (SLO), and full field and focal electroretinograms (ERGs).
      RESULTS: Three of the eight RP patients demonstrated possible improved light
      sensitivity during the initial months of follow-up. However, visual improvement
      disappeared between 3 and 13 months of follow-up. After transplantation, no
      subject showed any changes in the ERG recordings or SLO macular perimetry
      relative to their preoperative baseline. No patient experienced a retinal
      detachment, infection, or extensive bleeding. None of the patients developed
      retinal vasculitis or intraocular inflammation. In one RP patient, fluorescein
      angiography and fundus photography documented the formation and maturation of new
      host retinal vessels in the area of the transplant. CONCLUSIONS: Transplantation
      of fetal retinal photoreceptor suspensions into the subretinal space was achieved
      safely in nine subjects. Although a definite positive effect on visual function
      could not be demonstrated, the apparent high tolerance for graft tissue is
      promising for future efforts in the field of neural retinal transplantation.

PMID- 10967071
TI  - Attenuation of experimental proliferative vitreoretinopathy by inhibiting the
      platelet-derived growth factor receptor.
AB  - PURPOSE: The work from numerous laboratories has led to the idea that the growth
      factors such as platelet-derived growth factor (PDGF) contribute to proliferative
      vitreoretinopathy (PVR) in experimental models of the disease, as well as in
      humans. In support of this idea, the authors have previously reported that cells
      unable to respond to PDGF had a greatly reduced PVR potential, compared with PDGF
      responsive versions of the same cells. The goal of this study was to test the
      effect of blocking the output of the PDGF receptor in an experimental model of
      PVR. METHODS: Polymerase chain reaction-based site-directed mutagenesis was used
      to generate point mutations in the human PDGF alpha receptor (alphaPDGFR) cDNA,
      which resulted in single amino acid substitutions. These changes were based on
      naturally occurring point mutations in the c-kit receptor tyrosine kinase, which
      suppresses the function of wild-type c-kit. A truncated alphaPDGFR was also made,
      in which the receptor ended just after the juxtamembrane domain. As with the
      point mutants, truncated receptors have been shown to block the action of wild
      type receptors. All the alphaPDGFR mutants were introduced into cells that
      naturally express the wild-type receptor, and the PDGF-dependent output of the
      resultant cell lines was determined. In addition, the PVR potential of cell lines
      expressing the mutant receptors was tested in a PVR rabbit model. RESULTS:
      Although the mutants differed in their ability to suppress PDGF-dependent
      signaling of the wild-type receptor, each mutant effectively blocked cell cycle
      progression. When expressed in rabbit conjunctival fibroblasts, a cell line that
      effectively induces PVR, the mutant receptors blocked PVR to various degrees. The
      most effective receptor was the truncated mutant. CONCLUSIONS: These data suggest
      that the alphaPDGFR plays an important role in PVR. In addition, these mutant
      receptors appear to have therapeutic potential for prevention of this blinding
      disease.

PMID- 10967072
TI  - Metabolic dependence of photoreceptors on the choroid in the normal and detached
      retina.
AB  - PURPOSE: This article assesses the hypothesis that the high blood flow rate and
      low O(2) extraction associated with the choroidal circulation are metabolically
      necessary and explores the implications of the spatial relationship between the
      choroid and the photoreceptors for metabolism in the normal and detached retina.
      METHODS: The O(2) distribution across the retinal layers was previously measured
      with O(2)-sensitive microelectrodes in cat. Profiles were fitted to a diffusion
      model to obtain parameters characterizing photoreceptor O(2) demand. This was a
      study of simulations based on those parameters. RESULTS: Photoreceptor inner
      segments have a high O(2) demand (QO(2)), and they are far (20 to 30 microm) from
      the choroid. These unusual conditions require a large O(2) flux to the inner
      segments, which in turn requires high choroidal oxygen tension (PO(2)), high
      choroidal venous saturation (ScvO(2)), low choroidal O(2) oxygen extraction per
      unit volume of blood, and a choroidal blood flow (ChBF) of at least 500 ml/100 g
      min. Movement of the inner segments further from the choroid, which occurs in a
      retinal detachment, severely reduces the ability of the inner segments to obtain
      O(2), even for detachment heights as small as 100 microm. Depending on detachment
      height and assumptions about choroidal and inner retinal PO(2) during elevation
      of inspired O(2) (hyperoxia), hyperoxia is predicted to partially or fully
      restore photoreceptor QO(2) during a detachment. CONCLUSIONS: The choroid is not
      overperfused, but requires a high flow rate to satisfy the normal metabolic
      demand of the retina. Because the oxygenation of the photoreceptors is barely
      adequate under normal conditions, detachment has serious metabolic consequences.
      Hyperoxia is predicted to have clinical benefit during detachment.

PMID- 10967073
TI  - Novel rhodopsin mutations Gly114Val and Gln184Pro in dominant retinitis
      pigmentosa.
AB  - PURPOSE: To identify mutations in the rhodopsin gene in North American patients
      with autosomal dominant retinitis pigmentosa (ADRP) and to measure the proportion
      of cases with rhodopsin mutations. METHODS: Single-strand conformation
      polymorphism (SSCP) analysis and direct genomic sequencing were used to evaluate
      the coding region and intron splice sites of the rhodopsin gene for mutations in
      91 unrelated patients. RESULTS: Nineteen patients heterozygously carried a
      missense change in the rhodopsin gene (six with Pro23His, two with Pro347Leu, and
      one each with Thr17Met, Phe45Leu, Gly51Arg, Gly89Asp, Gly114Val, Arg135Trp,
      Pro171Leu, Gln184Pro, Phe220Leu, Ser297Arg, and Pro347Thr). All these missense
      changes were previously reported as causes for ADRP except for Gly114Val,
      Gln184Pro, and Phe220Leu, which were evaluated further by examining the relatives
      of index patients. The Gly114Val and Gln184Pro alleles cosegregated with ADRP as
      expected if they were pathogenic. Phe220Leu did not, indicating that it is not a
      cause of ADRP. CONCLUSIONS: Summation of the results of cases in this study with
      those of 272 unrelated cases of ADRP previously evaluated by our group shows that
      90 of 363 (25%) of cases were caused by rhodopsin mutations.

PMID- 10967074
TI  - Retinal dysfunction in basigin deficiency.
AB  - PURPOSE: To examine the retina of basigin (Bsg) knockout mice by
      electrophysiological and histologic methods and thereby to determine the possible
      function of Bsg in phototransduction and retinal development. METHODS: Scotopic
      and photopic electroretinograms (ERGs) were recorded from 11 wild-type, 12
      heterozygous, and 8 homozygous Bsg gene knockout mice of different ages. The
      retinas were also examined by histologic and immunolabeling methods. RESULTS: Bsg
      knockout mice of 5 to 41 weeks of age showed a decrease in the amplitude of all
      components of both the photopic and scotopic ERGs. In contrast, the fundus and
      the fluorescein fundus angiography and morphology of the retina at the light
      microscopic level appeared to be normal until 8 weeks of age in Bsg knockout
      mice. Thereafter, the length of outer segment and outer nuclear layers decreased
      with increasing age. Immunohistochemical analysis localized Bsg protein in a
      variety of cells in the retina, especially in the pigment epithelium, the upper
      outer plexiform layer and the inner segments of photoreceptor cells. CONCLUSIONS:
      The results demonstrated that both rod and cone function were severely affected
      from an early age by the targeted disruption of the Bsg gene. In spite of
      abnormal ERGs, the photoreceptor cells maintained normal morphology up to 8
      weeks. Thereafter, the photoreceptor cells degenerated gradually and were almost
      ablated by 41 weeks.

PMID- 10967075
TI  - Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral
      gene transfer.
AB  - PURPOSE: To determine whether local immunosuppression with Cyclosporin A can
      influence the survival of human fetal retinal pigment epithelium (RPE) xenografts
      in the rabbit's subretinal space. METHODS: Cultured human fetal RPE cells were
      transduced with the gene for green fluorescent protein (GFP) using a lentiviral
      vector. The RPE was transplanted into the subretinal space of rabbits that
      received intravitreal cyclosporine either by weekly injections (0. 25-0.5 mg) or
      by slow release (approximately 2 microg/d) from a capsule sutured into the
      vitreal cavity after prior cryopexy. The transplanted RPE was followed by GFP
      fluorescence scanning laser ophthalmoscopy and by histology of the transplant
      site. RESULTS: RPE xenografts in eyes receiving intravitreal cyclosporine
      survived longer (several months) than they did in control eyes without
      cyclosporine. Survival was as long with slow release capsules as it was with
      weekly intravitreal injections at much higher concentrations of cyclosporine.
      CONCLUSIONS: Local immunosuppression of the eye with cyclosporine prolongs the
      survival of RPE xenografts in the subretinal space of rabbits, implying that
      rejection involves activated T lymphocytes. Local immunosuppression with slow
      release capsules is as effective as weekly injections at much higher
      concentrations.

PMID- 10967076
TI  - Histologic correlation of human neural retinal transplantation.
AB  - PURPOSE: To describe the histologic findings of the transplanted eye of a 94-year
      old man with neovascular age-related macular degeneration, who 3 years earlier
      underwent subretinal transplantation of both a fetal neural retinal sheet and a
      retinal microaggregrate suspension. METHODS: Serial sections of the posterior
      segment of the eye and the transplanted areas were processed and studied by
      routine histologic techniques, including both light and transmission electron
      microscopy (TEM). Transplanted areas were also examined for the presence of
      glial, neuronal, and photoreceptor cell markers by standard immunohistochemical
      methods. RESULTS: After transplantation in this patient, there was no visual
      improvement. Light microscopic examination disclosed survival of the transplanted
      cells in the subretinal space with no evidence of inflammation or rejection. The
      neural retinal sheet transplant developed a layered configuration. The retinal
      pigment epithelium (RPE) was absent over much of the posterior pole, including
      the area of transplantation. TEM examination and immunohistochemical analysis
      disclosed the presence of neuronal and glial cells within the transplant. A few
      transplant neuronal cell processes overlying a focus of residual RPE cells were
      positive for S-antigen, but well-developed photoreceptor outer segments were not
      present. CONCLUSIONS: Long-term survival of transplanted neural retinal tissue
      can be achieved in human patients without immunosuppression. The lack of
      photoreceptor development in this patient may be the result of absent or
      dysfunctional RPE. Nonetheless, the long-term survival of grafted tissue in the
      human subretinal space in the absence of immunosuppressive treatment is promising
      for future efforts in the field of neural retinal transplantation.

PMID- 10967077
TI  - Retinal degeneration 6 (rd6): a new mouse model for human retinitis punctata
      albescens.
AB  - PURPOSE: To characterize the genetics and phenotype of a new mouse mutant with
      retinal degeneration, rd6, that is associated with extensive, scattered, small
      white retinal dots seen ophthalmoscopically. METHODS: The phenotype was
      characterized using ophthalmoscopy, fundus photography, electroretinography,
      light microscopy, immunocytochemistry, and electron microscopy. Genetic
      characterization and linkage analysis studies were performed using standard
      methods. RESULTS: The inheritance pattern of rd6 is autosomal recessive. Linkage
      analysis mapped rd6 to mouse Chromosome 9 approximately 24 cM from the
      centromere, suggesting that the human homolog may be on chromosome 11q23.
      Ophthalmoscopic examination of mice homozygous for rd6 revealed discrete
      subretinal spots oriented in a regular pattern across the retina. The retinal
      spots appeared by 8 to 10 weeks of age and persisted through advanced stages of
      retinal degeneration. Histologic examination revealed large cells in the
      subretinal space, typically juxtaposed to the retinal pigment epithelium. The
      white dots seen on fundus examination corresponded both in distribution and size
      to these large cells. By 3 months of age, the cells were filled with membranous
      profiles, lipofuscin-like material, and pigment. These cells reacted strongly
      with an antibody directed against a mouse macrophage-associated antigen.
      Photoreceptor cells progressively degenerated with age, and an abnormal
      electroretinogram was initially detected between 1 and 2 months of age.
      CONCLUSIONS: The fundi of mice homozygous for rd6 exhibit phenotypic similarities
      to the human flecked retinal disorder retinitis punctata albescens. Thus, rd6/rd6
      mice may be a model for understanding the etiology of this or similar disorders.
      The relationship between the aberrant subretinal cells and the concomitant
      photoreceptor degeneration remains to be established.

PMID- 10967079
TI  - Axonal regeneration of retinal ganglion cells depending on the distance of
      axotomy in adult hamsters.
AB  - PURPOSE: To examine the relationship between the distance of axotomy and axonal
      regeneration of injured retinal ganglion cells (RGCs) systematically and the
      effect of a predegenerated (pretransected or precrushed) peripheral nerve (PN)
      graft on axonal regeneration of RGCs axotomized at a definite distance (0.5 mm
      from the optic disc) in comparison with a normal PN graft. METHODS: The optic
      nerve (ON) was transected intraorbitally at 0.5, 1, 1.5, 2, or 3 mm or
      intracranially at 6 to 8 mm from the optic disc, and a PN graft was transplanted
      onto the ocular ON stump in adult hamsters. Four weeks after grafting, the number
      of RGCs regenerating their injured axons into the PN graft was investigated in
      all animals. RESULTS: The number of regenerating RGCs decreased significantly
      when the distance of axotomy increased from 0.5 to 7 mm. A precrushed PN graft
      was shown to enhance more injured RGCs to regenerate axons than a normal or
      pretransected PN graft. CONCLUSIONS: The distance of axotomy on the ON of adult
      hamsters is critical in determining the number of regenerating RGCs. Thus,
      experimental strategies to repair the damaged ON by PN transplantation is to
      attach a precrushed PN graft as close to the optic disc as possible to obtain
      optimal axonal regeneration of the axotomized RGCs.

PMID- 10967078
TI  - VEGF is major stimulator in model of choroidal neovascularization.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and
      is a major stimulatory factor for retinal neovascularization in ischemic
      retinopathies such as diabetic retinopathy. This study sought to determine if
      VEGF is a stimulatory factor in a murine model of choroidal neovascularization
      (CNV). METHODS: Mice with laser-induced ruptures in Bruch's membrane were treated
      with vehicle alone; a drug that inhibits both VEGF and platelet-derived growth
      factor (PDGF) receptor kinases; a drug that inhibits PDGF, but not VEGF receptor
      kinase; or genistein, a nonspecific kinase inhibitor. After two weeks, CNV was
      quantified and compared. RESULTS: Blockade of phosphorylation by VEGF and PDGF
      receptors caused dramatic, almost complete inhibition of CNV. Genistein also had
      an inhibitory effect, but less so than the VEGF/PDGF receptor blocker. Blockade
      of phosphorylation by PDGF receptors, but not VEGF receptors, had no significant
      effect on CNV. CONCLUSIONS: These data and our previous study, which demonstrated
      that a kinase inhibitor that blocks VEGF and PDGF receptors and several isoforms
      of protein kinase C causing dramatic inhibition of CNV, suggest that VEGF
      signaling plays a critical role in the development of CNV in this model. If
      safety is established, the effect of inhibiting VEGF receptor kinase activity
      should be investigated in patients with CNV.

PMID- 10967080
TI  - Cone differentiation with no photopigment coexpression.
AB  - PURPOSE: To decide whether the transitory coexpression of cone visual pigments
      described in the developing rat and gerbil retina is a universal feature of
      dichromatic mammalian species. METHODS: The rabbit, a species widely used in eye
      research, was selected for the study and a search made for the presence of cones
      that bound more than one cone antibody during the first postnatal week. To plot
      the densities of individual cone types and to colocalize the two visual pigments,
      immunocytochemistry on retinal wholemounts and consecutive tangential sections,
      respectively, were used. RESULTS: The sequence in which the visual pigments began
      to be expressed was the same as that observed in other mammals: first, rhodopsin;
      second, blue pigment; and last, green pigment. The striking increase in blue cone
      density numbers observed in the rat, however, did not occur in the rabbit.
      Instead, some days after the first blue cones appeared, the green cones also
      started to express their visual pigment, and this cone type soon outnumbered the
      blue cones. Within the limits of the immunocytochemical method, it was
      established that unlike the developing rat, the presence of double-labeled cones
      was not a character of the rabbit retina. CONCLUSIONS: Visual pigment
      coexpression is an interesting phenomenon of retinal development, however, it is
      not the exclusive scenario of photoreceptor differentiation. Each species must be
      carefully studied before deciding whether its retinal cones synthesize both
      pigments during retinal development.

PMID- 10967081
TI  - Differential susceptibility of retinal ganglion cells to reactive oxygen species.
AB  - PURPOSE: Retinal light exposure is a source of oxidative stress, and retinal
      cells contain molecules that scavenge or inactivate reactive oxygen species
      (ROS). Yet, ROS also play a role in signal transduction, and some retinal cells
      (e.g., neurotrophin-dependent retinal ganglion cells, RGCs) may use ROS as part
      of the signaling process for cell death. RGCs might therefore have specialized
      mechanisms for regulating ROS levels. The hypothesis that RGCs might regulate ROS
      differently from other retinal cells was tested by studying their differential
      response to oxidative stress in vitro. METHODS: RGCs were retrogradely labeled by
      injecting the fluorescent tracer DiI into the superior colliculi of postnatal day
      2 through 4 Long-Evans rats. At postnatal days 7 through 9 the retinas were
      dissociated with papain and cultured with and without specific ROS-generating
      systems and/or scavengers. RGCs were identified by their DiI positivity using
      rhodamine filters. Living cells, determined by metabolism of calcein-AM viewed
      with fluorescein filters, were counted in triplicate. Degenerate reverse
      transcription-polymerase chain reaction (RT-PCR) using primers specific to
      peroxidase homology regions was used to survey for novel peroxidases expressed
      within normal retinas. RESULTS: Compared with other retinal cells, RGCs were
      remarkably resistant to cell death induced by superoxide anion, hydrogen
      peroxide, or hydroxyl radical. Catalase counteracted the effect of each ROS
      generating system on retinal cells, consistent with damage occurring via a
      hydrogen peroxide intermediate. Aminotriazole, L-buthionine sulfoximine, and
      sodium azide partly abrogated the RGC resistance to oxidative stress, suggesting
      that this resistance may be mediated by catalase and/or glutathione peroxidase. A
      limited expression survey within the retina using degenerate RT-PCR did not
      demonstrate novel peroxidases. CONCLUSIONS: These data suggest a role for one or
      more endogenous peroxidases within RGCs, which could possibly be protective under
      conditions of axonal damage. Exploration of the unique characteristics of RGC
      resistance and susceptibility to injury may help in better understanding the
      pathophysiology of diseases associated with primary axonal damage.

PMID- 10967082
TI  - Energy metabolism in human retinal Muller cells.
AB  - PURPOSE: To measure selected parameters of energy metabolism and adenosine
      triphosphate (ATP) production in passaged monolayer cultures of human retinal
      glial (Muller) cells to assess the effects of varying substrate and oxygen
      availability on the biochemistry and histologic integrity of these cells.
      METHODS: Confluent Muller cell cultures were incubated for up to 4 hours at 37
      degrees C in a modified minimal essential medium (no serum) under aerobic or
      mitochondrial-inhibited conditions in the presence and absence of 5 mM glucose or
      in the presence of lactate, pyruvate, glutamate, or glutamine. Cellular ATP
      levels, lactic acid production, and (14)CO(2) production from labeled glucose or
      glutamate were measured along with an examination of cellular morphology.
      Immunohistochemistry with antibodies to glial cell-specific proteins was also
      performed. Cells were positive for vimentin, but negative for glial fibrillary
      acidic protein and glutamine synthetase. RESULTS: Human Muller cells maintained
      ATP content aerobically at the same level for 4 hours in the presence and absence
      of glucose. ATP content was also maintained anaerobically at a value equal to
      that found aerobically, but only in the presence of glucose. ATP content in human
      Muller cells declined to a very low level when glycolysis was blocked by
      iodoacetate, and inclusion of lactate, pyruvate, glutamate, or glutamine did not
      restore the level of ATP. Aerobically, lactic acid production accounted for 99%
      of the total glucose used, whereas the oxidation of glucose by the mitochondria
      accounted for only 1%. When mitochondria were inhibited with antimycin A, there
      was only a modest (1.3-fold) increase in the rate of lactic acid production. No
      significant differences were found in the histologic appearance of the cells
      after mitochondrial blockade, but there was massive death of cells after
      inhibition of glycolysis with iodoacetate. CONCLUSIONS: These results suggest
      that, in the presence of glucose and oxygen, cultured Muller cells obtain their
      ATP principally from glycolysis and have a low rate of oxygen consumption. This
      metabolic pattern may spare oxygen for retinal neurons, particularly in the inner
      nuclear and ganglion cell layers under normal physiological conditions.
      Furthermore, retinal Muller cells in culture are resistant to anoxia or absence
      of glucose, which provides a basis for understanding why Muller cells are less
      susceptible than neurons to ischemia or hypoglycemia.

PMID- 10967083
TI  - Expression of somatostatin subtype 1 receptor in the rabbit retina.
AB  - PURPOSE: To detect mRNAs for somatostatin (somatotropin release-inhibiting factor
      [SRIF]) receptor subtypes 1 to 5 (sst(1) through sst(5)) in rabbit retinas by
      reverse transcription-polymerase chain reaction (RT-PCR) and to investigate the
      distribution of sst(1) by single- and double-label immunocytochemistry. METHODS:
      Semiquantitative RT-PCR using sst-specific primers from mouse sequences was
      performed. sst(1) was localized using a polyclonal antiserum directed to human
      sst(1) in cryostat sections of retinas from either normal or optic nerve
      transected animals. Immunolabeled cell sizes and densities were measured in
      wholemounted retinas using computer-assisted image analysis. Double-label
      immunofluorescence was performed using the sst(1) antiserum in conjunction with
      monoclonal antibodies directed to SRIF, tyrosine hydroxylase (TH), parvalbumin
      (PV), or gamma-aminobutyric acid (GABA). RESULTS: With RT-PCR it was found that
      all five sst mRNAs were expressed in the rabbit retina, with highest levels of
      sst(1) mRNA. sst(1) immunolabeling was localized to amacrine cells in the
      proximal inner nuclear layer (INL) of all retinal regions and to displaced
      amacrine cells in the ganglion cell layer (GCL) of the ventral retina. Some large
      sst(1)-immunoreactive (IR) somata were also present in the GCL. They were not
      observed after optic nerve transection. Double-label immunofluorescence showed
      sst(1) expression by all TH-IR amacrine cells and by other amacrine cells that
      were neither PV-IR nor GABA-IR. In addition, sst(1) was expressed by all SRIF
      containing displaced amacrine cells. CONCLUSIONS: All five sst mRNAs are
      expressed in the rabbit retina. The localization of sst(1) suggests that it may
      mediate SRIF actions onto amacrine (including dopaminergic) and sparse ganglion
      cells. sst(1) expression in SRIF-IR cells suggests that this receptor may also
      act as an autoreceptor.

PMID- 10967084
TI  - P23H rhodopsin transgenic rat: correlation of retinal function with
      histopathology.
AB  - PURPOSE: To correlate retinal functional changes with structural changes in P23H
      rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa.
      METHODS: P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were
      studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a
      wave transduction modeling. RESULTS: Both line 1 (faster degeneration) and line 3
      (slower degeneration) showed progressive rod outer segment (ROS) shortening and
      outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude
      (Vb(max)) decreased with age, but b-wave threshold remained constant within each
      line despite progressive ONL thinning and ROS shortening. The only exception was
      in line 1 at 29 weeks, which showed a slight threshold change relative to earlier
      ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive
      than the b-wave in reflecting histologic degeneration. Va(max) was linearly
      proportional to the product of (ROS x ONL) across a two log unit range of data
      combined from both lines. The photopic b-wave was normal for both lines until the
      ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines,
      and dark-adaptation recovery after bleaching rhodopsin was normal. CONCLUSIONS:
      The P23H transgenic rat has a slow rod degeneration with initially normal cone
      function, consistent with clinical findings of P23H patients. However, the normal
      bleach recovery and the normal phototransduction sensitivity in this rat model
      are different from human P23H disease. a-Wave measures were more sensitive than
      the b-wave for tracking changes. b-Wave threshold was inexplicably poor for
      tracking degeneration. Although line 1 degenerated faster than line 3, the
      functional-structural correlates were the same. The tight linear relationship
      between saturated a-wave amplitude and the product of (ROS x ONL) indicates that
      the density of cGMP-gated channels per unit ROS plasma membrane area remains
      constant over a wide range of degenerations.

PMID- 10967085
TI  - Post-treatment at 12 or 18 hours with 3-aminobenzamide ameliorates retinal
      ischemia-reperfusion damage.
AB  - PURPOSE: The window of protection afforded by 3-aminobenzamide (3-ABA), a poly
      (ADP-ribose) polymerase (PARP) inhibitor, against apoptotic loss of inner retinal
      elements after ischemia-reperfusion insult in rats was examined. METHODS:
      Ischemia-reperfusion injury to the retinas in albino Lewis rats was induced by
      elevated intraocular pressure (IOP) through cannulation of the anterior chamber
      with a needle connected to a saline column delivering a pressure of 110 mm Hg.
      The ischemic period was held at 60 minutes, and reperfusion was established
      immediately afterward. 3-Aminobenzamide (3-ABA) was administered intravitreally
      at 0, 4, 8, 12, 18, or 24 hours after reperfusion and its effect evaluated by
      morphology and morphometry of the inner retinas at 7 days after reperfusion.
      Immunohistochemistry of poly-(ADP-ribose), a product of PARP activity, and
      Western blot analysis for PARP were performed on retinas at 0, 4, 8, 12, 18, and
      24 hours after reperfusion. RESULTS: Morphology and morphometry showed
      significantly better preserved inner retinas in animals receiving 3-ABA between
      12 and 18 hours after reperfusion. Immunohistochemical study of poly-(ADP-ribose)
      showed elevated levels at the retinal ganglion cell layer and the inner nuclear
      layer at 12 and 18 hours after reperfusion. Western blot analysis of PARP showed
      a notable increase in the 116-kDa band (PARP) from 4 to 18 hours after
      reperfusion. CONCLUSIONS: Administration of 3-ABA at 12 or 18 hours after
      ischemia, when there was accumulation of poly-(ADP-ribose) in the inner retina,
      significantly ameliorated retinal ischemia-reperfusion injury. These findings,
      together with earlier reports from our laboratory, are consistent with a late and
      pivotal role of PARP in apoptotic loss of inner retinal elements after ischemia
      reperfusion insult to the retina.

PMID- 10967086
TI  - Time at confluence for human RPE cells: effects on the adherens junction and in
      vitro wound closure.
AB  - PURPOSE: To determine how time at confluence affects the properties of cultured
      human retinal pigment epithelium (RPE) cells, with emphasis on the adherens
      junction. METHODS: Cultures were maintained at confluence without passage for
      intervals to several months. Adherens junction proteins (N-cadherin, E-cadherin,
      alpha-catenin, beta-catenin, plakoglobin, and actin) and the proliferation marker
      Ki-67 were localized in the cultures by fluorescence microscopy, and in vitro
      wound healing was compared. Adherens junctions were analyzed for protein
      solubility in detergent buffers and sensitivity to disruption by treatment with
      anti-cadherin antibodies and low calcium conditions. RESULTS: Compared with
      cultures in early-confluence (2-3 days), postconfluent cultures (weeks) had more
      mature adherens junctions characterized by a circumferential (rather than linear)
      actin organization, and a zonular (rather than punctate) distribution of more
      detergent resistant cadherin and catenins. Postconfluent cultures also had fewer
      Ki-67-positive cells and a higher cell packing density. Early-confluence cells
      migrated into in vitro wounds as dissociated single cells, whereas postconfluent
      cells moved as contiguous sheets, retaining an intact junction during wound
      induced cell migration and proliferation. Mature junctions were not disrupted by
      treatment of living cells with N-cadherin antibodies, which bound to and remained
      detectable at junctions for several days. Calcium withdrawal displaced N-cadherin
      from mature junctions and rendered it more soluble, but the dominant
      circumferential pattern of actin was stable. Restoration of medium calcium
      resulted in a rapid (hours) recovery of a nearly complete zonular pattern of
      insoluble N-cadherin. CONCLUSIONS: Over long postconfluent periods, cultured RPE
      cells became more growth quiescent, and intercellular cadherin adhesions became
      more stable, exhibiting increased resistance to calcium removal and greater
      retention of junctional integrity during in vitro wound closure. Consideration
      should be given to whether the behavior of RPE cells in postconfluent cultures,
      where intercellular adhesions are more mature, more closely simulates RPE cells
      in situ than cells in early-confluence cultures, which are more commonly used for
      analysis.

PMID- 10967087
TI  - Large phase differences between L-cone- and M-cone-driven electroretinograms in
      retinitis pigmentosa.
AB  - PURPOSE: To study the dynamics and interactions of the signals originating in the
      long- (L-) and middle (M)-wavelength-sensitive cone pathways in patients with
      retinitis pigmentosa (RP). METHODS: Twenty-six patients with RP and 29 normal
      subjects participated in the study. Electroretinographic (ERG) responses were
      measured to stimuli that modulated exclusively the L- or the M-cones or the two
      simultaneously (both in-phase and in counter-phase) with varying ratios of L- to
      M-cone contrasts. S-cones were not modulated. RESULTS: The data of the normal
      subjects and of the patients can be described by a model in which the amplitudes
      and the phases of the signals originating in the L- and M-cones are vector
      summed. In the RP patients, there was a general reduction in ERG sensitivity. The
      L-cone-driven ERG response was significantly delayed, whereas the M-cone-driven
      ERG response was phase advanced. CONCLUSIONS: Large dynamic differences between L
      and M-cone-driven ERGs can be detected in RP. As a result, the interaction
      between the L- and M-cone systems, when modulated simultaneously at 30 Hz, is
      subtractive in RP patients and additive in normal subjects. Our data show that
      the use of only a standard white flicker ERG might lead to a misinterpretation of
      the mechanisms involved in retinal disorders, because the phases of different
      cone-driven responses are not considered.

PMID- 10967089
TI  - Techniques, tools, and models in vision research

PMID- 10967088
TI  - Multifocal oscillatory potentials in type 1 diabetes without retinopathy.
AB  - PURPOSE: To study multifocal recordings of oscillatory potentials (m-OPs) in
      diabetic (Type 1) eyes that have no visible fundus alterations, to ascertain
      whether topographical changes in sensitivity are evident when compared with
      recordings from control subjects. METHODS: The Visual Evoked Response Imaging
      System (VERIS; EDI, San Diego, CA) system was used to elicit m-OPs from 61
      independent areas, subtending the central 30 degrees of the retina, from 24 eyes
      of 12 patients with diabetes without retinopathy and from 26 eyes of 14 control
      subjects. For each group of subjects, the mean first- and second-order (first
      slice) kernel components of the responses for one eye, randomly chosen from each
      subject, were analyzed and compared for a retinal ring analysis and for an
      analysis of retinal quadrants. RESULTS: Both first- and second-order kernel
      responses of the diabetic group show significant delays in the implicit times of
      some of the m-OPs, compared with those of the control group. No significant
      changes in amplitude were found. For the first-order component, significant
      differences are found for both potentials between 5 degrees and 22 degrees
      eccentricity, for the nasal retina, and for one of the potentials for the
      remaining retinal areas. In the second-order kernel responses, the differences
      are significant for two of the three potentials in the midperiphery between 5
      degrees and 13 degrees eccentricity, with the central potential being
      significantly delayed in all rings and quadrants. CONCLUSIONS: Patients with
      diabetes without retinopathy show prolonged latencies in m-OP recordings. This
      indicates an alteration in inner retinal sensitivity that can be explained by an
      impaired rod-cone interaction.

PMID- 10967090
TI  - Glutamate is not a messenger in insulin secretion.
AB  - Experiments do not support a recent claim that glutamate formed from the
      amination of citric acid cycle-derived alpha-ketoglutarate is a messenger in
      glucose-induced insulin secretion (Maechler, P., and Wollheim, C. (1999) Nature
      402, 685-689). Glucose, leucine, succinic acid methyl ester, and alpha
      ketoisocaproic acid all markedly stimulate insulin release but do not increase
      glutamate levels in pancreatic islets. Increasing the intracellular glutamate
      levels to 10-fold higher than basal levels by adding glutamine to islets does not
      stimulate insulin release. When leucine, in addition to glutamine, is applied to
      islets, insulin release is almost as high as with glucose alone. This is
      consistent with the known ability of leucine to allosterically activate glutamate
      deamination by glutamate dehydrogenase, which can supply alpha-ketoglutarate to
      the citric acid cycle. Experiments with mitochondria from pancreatic islets
      suggest that flux through the glutamate dehydrogenase reaction is quiescent
      during glucose-induced insulin secretion. These experiments support the
      traditional idea that when insulin release is associated with flux through
      glutamate dehydrogenase, the flux is in the direction of alpha-ketoglutarate.

PMID- 10967092
TI  - Biochemical characterization of an ATPase activity associated with the large
      packaging subunit gp17 from bacteriophage T4.
AB  - Double-stranded DNA-packaging in icosahedral bacteriophages is believed to be
      driven by a packaging "machine" constituted by the portal protein and the two
      packaging/terminase proteins assembled at the unique portal vertex of the empty
      prohead shell. Although ATP hydrolysis is evidently the principal driving force,
      which component of the packaging machinery functions as the translocating ATPase
      has not been elucidated. Evidence suggests that the large packaging subunit is a
      strong candidate for the translocating ATPase. We have constructed new phage T4
      terminase recombinants under the control of phage T7 promoter and overexpressed
      the packaging/terminase proteins gp16 and gp17 in various configurations. The
      hexahistidine-tagged-packaging proteins were purified to near homogeneity by
      Ni(2+)-agarose chromatography and were shown to be highly active for packaging
      DNA in vitro. The large packaging subunit gp17 but not the small subunit gp16
      exhibited an ATPase activity. Although gp16 lacked ATPase activity, it enhanced
      the gp17-associated ATPase activity by >50-fold. The gp16 enhancement was
      specific and was due to an increased catalytic rate for ATP hydrolysis. A
      phosphorylated gp17 was demonstrated under conditions of low catalytic rates but
      not under high catalytic rates in the presence of gp16. The data are consistent
      with the hypothesis that a weak ATPase is transformed into a translocating ATPase
      of high catalytic capacity after assembly of the packaging machine.

PMID- 10967091
TI  - Cellugyrin is a marker for a distinct population of intracellular Glut4
      containing vesicles.
AB  - Although Glut4 traffic is routinely described as translocation from an
      "intracellular storage pool" to the plasma membrane, it has been long realized
      that Glut4 travels through at least two functionally distinct intracellular
      membrane compartments on the way to and from the cell surface. Biochemical
      separation and systematic studies of the individual Glut4-containing compartments
      have been limited by the lack of appropriate reagents. We have prepared a
      monoclonal antibody against a novel component protein of Glut4 vesicles and have
      identified this protein as cellugyrin, a ubiquitously expressed homologue of a
      major synaptic vesicle protein, synaptogyrin. By means of sucrose gradient
      centrifugation, immunoadsorption, and confocal microscopy, we have shown that
      virtually all cellugyrin is co-localized with Glut4 in the same vesicles.
      However, unlike Glut4, cellugyrin is not re-distributed to the plasma membrane in
      response to insulin stimulation, and at least 40-50% of the total population of
      Glut4 vesicles do not contain this protein. We suggest that cellugyrin represents
      a specific marker of a functionally distinct population of Glut4 vesicles that
      permanently maintains its intracellular localization and is not recruited to the
      plasma membrane by insulin.

PMID- 10967093
TI  - Male-specific IDGF, a novel gene encoding a membrane-bound extracellular
      signaling molecule expressed exclusively in testis of Drosophila melanogaster.
AB  - We identified a novel gene of Drosophila melanogaster, Male-specific IDGF (MSI),
      encoding a transmembrane signaling molecule with exclusive expression in the
      testis. This molecule (MSI) contains a single transmembrane domain and has 35%
      amino acid identity with insect-derived growth factor (IDGF), a soluble growth
      factor for embryonic cells of the flesh fly, Sarcophaga peregrina. When MSI was
      exogenously expressed in Schneiders's line 2 cells, it was shown to be localized
      on the cell surface and exhibits growth factor activity, suggesting that MSI is a
      membrane-bound extracellular signaling molecule. Gene expression studies revealed
      that MSI mRNA was restricted to mature primary spermatocytes, whereas MSI was
      detected in the cells at the later developmental stages. Analysis using four
      meiotic arrest mutants, aly, can, mia, and sa suggested that MSI is involved in
      spermiogenesis, the final differentiation step of spermatogenesis. These results
      suggest that MSI is an extracellular signaling molecule participating in
      spermatogenesis and is a new member of the IDGF family.

PMID- 10967094
TI  - Characterization of TCL, a new GTPase of the rho family related to TC10
      andCcdc42.
AB  - GTPases of the Rho family control a wide variety of cellular processes such as
      cell morphology, motility, proliferation, differentiation, and apoptosis. We
      report here the characterization of a new Rho member, which shares 85% and 78%
      amino acid similarity to TC10 and Cdc42, respectively. This GTPase, termed as
      TC10-like (TCL) is encoded by an unexpectedly large locus, made of five exons
      spanning over 85 kilobases on human chromosome 14. TCL mRNA is 2.5 kilobases long
      and is mainly expressed in heart. In vitro, TCL shows rapid GDP/GTP exchange and
      displays higher GTP dissociation and hydolysis rates than TC10. Using the yeast
      two-hybrid system and GST pull-down assays, we show that GTP-bound but not GDP
      bound TCL protein directly interacts with Cdc42/Rac interacting binding domains,
      such as those found in PAK and WASP. Despite its overall similarity to TC10 and
      Cdc42, the constitutively active TCL mutant displays distinct morphogenic
      activity in REF-52 fibroblasts, producing large and dynamic F-actin-rich ruffles
      on the dorsal cell membrane. Interestingly, TCL morphogenic activity is blocked
      by dominant negative Rac1 and Cdc42 mutants, suggesting a cross-talk between
      these three Rho GTPases.

PMID- 10967095
TI  - Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for
      direct and indirect pathways.
AB  - The hypothalamic-pituitary-thyroid axis is down-regulated during starvation, and
      falling levels of leptin are a critical signal for this adaptation, acting to
      suppress preprothyrotropin-releasing hormone (prepro-TRH) mRNA expression in the
      paraventricular nucleus of the hypothalamus. This study addresses the mechanism
      for this regulation, using primary cultures of fetal rat hypothalamic neurons as
      a model system. Leptin dose-dependently stimulated a 10-fold increase in pro-TRH
      biosynthesis, with a maximum response at 10 nm. TRH release was quantified using
      immunoprecipitation, followed by isoelectric focusing gel electrophoresis and
      specific TRH radioimmunoassay. Leptin stimulated TRH release by 7-fold.
      Immunocytochemistry revealed that a substantial population of cells expressed TRH
      or leptin receptors and that 8-13% of those expressing leptin receptors
      coexpressed TRH. Leptin produced a 5-fold induction of luciferase activity in CV
      1 cells transfected with a TRH promoter and the long form of the leptin receptor
      cDNA. Although the above data are consistent with a direct ability of leptin to
      promote TRH biosynthesis through actions on TRH neurons, addition of alpha
      melanocyte-stimulating hormone produced a 3.5-fold increase in TRH biosynthesis
      and release, whereas neuropeptide Y treatment suppressed pro-TRH biosynthesis
      approximately 3-fold. Furthermore, the melanocortin-4 receptor antagonist SHU9119
      partially inhibited leptin-stimulated TRH release from the neuronal culture.
      Consequently, our data suggest that leptin regulates the TRH neurons through both
      direct and indirect pathways.

PMID- 10967096
TI  - Identification of osteoblast/osteocyte factor 45 (OF45), a bone-specific cDNA
      encoding an RGD-containing protein that is highly expressed in osteoblasts and
      osteocytes.
AB  - We describe the cloning and characterization of a novel bone-specific cDNA
      predicted to encode an extracellular matrix protein. This cDNA was identified by
      subtractive hybridization based upon its high expression in bone marrow-derived
      osteoblasts. By Northern blot analysis, we detected a single 2-kilobase mRNA
      transcript in bone, whereas no expression was detected in other tissues.
      Immunohistochemistry revealed that the protein was expressed highly in osteocytes
      within trabecular and cortical bone. RNA and protein expression analysis using in
      vivo marrow ablation as a model of bone remodeling demonstrated that this gene
      was expressed only in cells that were embedded within bone matrix in contrast to
      the earlier expression of known osteoblast markers. The cDNA was predicted to
      encode a serine/glycine-rich secreted peptide containing numerous potential
      phosphorylation sites and one RGD sequence motif. The interaction of RGD domain
      containing peptides with integrins has been shown previously to regulate bone
      remodeling by promoting recruitment, attachment, and differentiation of
      osteoblasts and osteoclasts. Secretion of this RGD-containing protein from
      osteocytes has the potential to regulate cellular activities within the bone
      environment and thereby may impact bone homeostasis. We propose the name OF45
      (osteoblast/osteocyte factor of 45 kDa) for this novel cDNA.

PMID- 10967097
TI  - The Na+/Ca2+ exchanger NCX1 has oppositely oriented reentrant loop domains that
      contain conserved aspartic acids whose mutation alters its apparent Ca2+
      affinity.
AB  - We examined the membrane topology and functional importance of residues in
      regions of the Na(+)/Ca(2+) exchanger NCX1 encompassing the conserved internal
      alpha repeats by substituted cysteine scanning analysis and kinetic analysis of
      site-directed mutants. The results suggest that both the alpha-1 repeat and a
      region encompassing the alpha-2 repeat and its immediately C-terminal segment
      contain reentrant loop domains, each oriented in an opposite direction with
      respect to the membrane. We found that single or multiple mutations of six
      residues including Asn-125 and conserved aspartates Asp-130, Asp-825, and Asp-829
      in the alpha repeat reentrant domains reduce the apparent affinity of the
      exchanger for extracellular Ca(2+) by up to 6-fold. In contrast, the triple
      cysteine mutation D130C/D825C/D829C did not influence the current-voltage (I-V)
      relationship of the exchange current. Cysteine accessibility scanning with
      different thiol modifiers suggested that N125C, D130C, and D825C may be located
      in a restricted aqueous space in the membrane accessible only to ions when
      examined with external probes, although N125C and D825C were previously shown to
      be internally accessible during exchange reaction. The results suggest that these
      reentrant domains in the alpha repeats may participate in the formation of the
      ion transport pathway in the exchanger with some of the aspartates possibly
      lining it or located close to it.

PMID- 10967098
TI  - Lack of palmitoylation redirects p59Hck from the plasma membrane to p61Hck
      positive lysosomes.
AB  - Hck, a protein-tyrosine kinase of phagocytes, is the unique member of the Src
      family expressed under two alternatively translated isoforms differing in their N
      terminal site of acylation: p61(Hck) has an additional 21-amino acid sequence
      comprising a single myristoylation motif, whereas p59(Hck) N terminus has
      myristoylation and palmitoylation sites. To identify the molecular determinants
      involved in the targeting of each isoform, they were fused to GFP and expressed
      in HeLa and CHO cells. p61(Hck) was associated with lysosomal vesicles, whereas
      p59(Hck) was found at the plasma membrane and to a low extent associated with
      lysosomes. Their unique N-terminal domains were sufficient to target GFP to the
      corresponding intracellular compartments. Mutation of the palmitoylation site of
      p59(Hck) redirected this isoform to lysosomes, indicating that the palmitoylation
      state governs the association of p59(Hck) with the plasma membrane or with
      lysosomes. In addition, both isoforms and the nonpalmitoylated p59(Hck) mutant
      were found on the Golgi apparatus, suggesting a role of this organelle in the
      subcellular sorting of Hck isoforms. Regarding their subcellular localizations,
      we propose that bi-acylated p59(Hck) might transduce plasma membrane receptor
      signals, whereas p61(Hck) and the nonpalmitoylated p59(Hck) might control the
      biogenesis of phagolysosomes, two functions yet proposed for Hck in phagocytes.

PMID- 10967099
TI  - Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis
      and defects in heartbeat.
AB  - Ca(2+), which enters cardiac myocytes through voltage-dependent Ca(2+) channels
      during excitation, is extruded from myocytes primarily by the Na(+)/Ca(2+)
      exchanger (NCX1) during relaxation. The increase in intracellular Ca(2+)
      concentration in myocytes by digitalis treatment and after ischemia/reperfusion
      is also thought to result from the reverse mode of the Na(+)/Ca(2+) exchange
      mechanism. However, the precise roles of the NCX1 are still unclear because of
      the lack of its specific inhibitors. We generated Ncx1-deficient mice by gene
      targeting to determine the in vivo function of the exchanger. Homozygous Ncx1
      deficient mice died between embryonic days 9 and 10. Their hearts did not beat,
      and cardiac myocytes showed apoptosis. No forward mode or reverse mode of the
      Na(+)/Ca(2+) exchange activity was detected in null mutant hearts. The Na(+)
      dependent Ca(2+) exchange activity as well as protein content of NCX1 were
      decreased by approximately 50% in the heart, kidney, aorta, and smooth muscle
      cells of the heterozygous mice, and tension development of the aortic ring in
      Na(+)-free solution was markedly impaired in heterozygous mice. These findings
      suggest that NCX1 is required for heartbeats and survival of cardiac myocytes in
      embryos and plays critical roles in Na(+)-dependent Ca(2+) handling in the heart
      and aorta.

PMID- 10967100
TI  - Nadrin, a novel neuron-specific GTPase-activating protein involved in regulated
      exocytosis.
AB  - It has been proposed that the cortical actin filament networks act as a cortical
      barrier that must be reorganized to enable docking and fusion of the synaptic
      vesicles with the plasma membranes. We identified a novel neuron-associated
      developmentally regulated protein, designated as Nadrin. Expression of Nadrin is
      restricted to neurons and correlates well with the differentiation of neurons.
      Nadrin has a unique structure; it contains a GTPase-activating protein (GAP)
      domain for Rho family GTPases, a potential coiled-coil domain, and a succession
      of 29 glutamines. In vitro the GAP domain activates RhoA, Rac1, and Cdc42
      GTPases. Expression of Nadrin in NIH3T3 cells markedly reduced the number of the
      actin stress fibers and the formation of the ruffled membranes, suggesting that
      Nadrin regulates actin filament reorganization. In PC12 cells, Nadrin colocalized
      with synaptotagmin in the neurite termini and also with cortical actin filaments
      in the subplasmalemmal regions. Expression of Nadrin or its mutant composed of
      the coiled-coil and GAP domain enhanced Ca(2+)-dependent exocytosis of PC12
      cells, but a mutant lacking the GAP domain inhibited exocytosis. These results
      suggest that Nadrin plays a role in regulating Ca(2+)-dependent exocytosis, most
      likely by catalyzing GTPase activity of Rho family proteins and by inducing the
      reorganization of the cortical actin filaments.

PMID- 10967101
TI  - Differential protective activity of alpha A- and alphaB-crystallin in lens
      epithelial cells.
AB  - alphaA- and alphaB-crystallins are molecular chaperones expressed at low levels
      in lens epithelial cells, and their expression increases dramatically during
      differentiation to lens fibers. However, the functions of alphaA- and alphaB
      crystallins in lens epithelial cells have not been studied in detail. In this
      study, the relative ability of alphaA- and alphaB-crystallin, in protecting lens
      epithelial cells from apoptotic cell death was determined. The introduction of
      alphaA-crystallin in the transformed human lens epithelial (HLE) B-3 lens
      epithelial cell line (which expresses low endogenous levels of alphaB-crystallin)
      led to a nearly complete protection of cell death induced by staurosporine, Fas
      monoclonal antibody, or the cytokine tumor necrosis factor alpha. To further
      study the relative protective activities of alphaA- and alphaB-crystallins, we
      created a cell line derived from alphaA-/-alphaB-/- double knockout mouse lens
      epithelia by infecting primary cells with Ad12-SV40 hybrid virus. The transformed
      cell line alphaAalphaBKO1 derived from alphaA/alphaB double knockout cells was
      transfected with alphaA- or alphaB-crystallin cDNA contained in pCIneo mammalian
      expression vector. Cells expressing different amounts of either alphaA-crystallin
      or alphaB-crystallin were isolated. The ability of alphaA- or alphaB-crystallin
      to confer protection from apoptotic cell death was determined by annexin labeling
      and flow cytometry of staurosporine- or UVA- treated cells. The results indicate
      that the anti-apoptotic activity of alphaA-crystallin was two to three-fold
      higher than that of alphaB-crystallin. Our work suggests that comparing the in
      vitro annexin labeling of lens epithelial cells is an effective way to measure
      the protective activity of alphaA- and alphaB-crystallin. Since the expression of
      alphaA-crystallin is largely restricted to the lens, its greater protective
      effect against apoptosis suggests that it may play a significant role in
      protecting lens epithelial cells from stress.

PMID- 10967103
TI  - Hic, a novel surface protein of Streptococcus pneumoniae that interferes with
      complement function.
AB  - The important human pathogen Streptococcus pneumoniae was found to absorb factor
      H, an inhibitor of complement, from human plasma. We identified the gene encoding
      a novel surface protein, factor H-binding inhibitor of complement (Hic), in the
      pspC locus of type 3 pneumococci. Unlike PspC proteins in other serotypes, Hic is
      anchored to the cell wall by means of an LPXTG motif, and the overall sequence
      homology to various PspC proteins is low. However, the NH(2)-terminal region
      showed significant homology to the NH(2)-terminal region of several PspC
      proteins. A fragment of Hic, covering this homologous region, was expressed as a
      glutathione S-transferase (GST) fusion protein. GST:Hic(39-261) bound
      radiolabeled factor H and inhibited binding of factor H to pneumococci of
      different serotypes. Interaction kinetics between GST:Hic(39-261) and factor H
      were studied with surface plasmon resonance and showed a high affinity binding
      (K(A) = 5 x 10(7), K(D) = 2.3 x 10(-)(8)). Mutant pneumococci lacking Hic showed
      no absorption of factor H in human plasma and no binding of radiolabeled factor
      H, suggesting that Hic is responsible for factor H-binding in type 3 pneumococci.
      Factor H-dependent inhibition of the alternative pathway was not diminished by
      the presence of GST:Hic(39-261). In addition, an intrinsic inhibitory effect of
      Hic is suggested.

PMID- 10967102
TI  - Crystal structure of a deacylation-defective mutant of penicillin-binding protein
      5 at 2.3-A resolution.
AB  - Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a d-alanine
      carboxypeptidase, cleaving the C-terminal d-alanine residue from cell wall
      peptides. Like all PBPs, PBP 5 forms a covalent acyl-enzyme complex with beta
      lactam antibiotics; however, PBP 5 is distinguished by its high rate of
      deacylation of the acyl-enzyme complex (t(12) approximately 9 min). A Gly-105 -->
      Asp mutation in PBP 5 markedly impairs this beta-lactamase activity
      (deacylation), with only minor effects on acylation, and promotes accumulation of
      a covalent complex with peptide substrates. To gain further insight into the
      catalytic mechanism of PBP 5, we determined the three-dimensional structure of
      the G105D mutant form of soluble PBP 5 (termed sPBP 5') at 2.3 A resolution. The
      structure is composed of two domains, a penicillin binding domain with a striking
      similarity to Class A beta-lactamases (TEM-1-like) and a domain of unknown
      function. In addition, the penicillin-binding domain contains an active site loop
      spatially equivalent to the Omega loop of beta-lactamases. In beta-lactamases,
      the Omega loop contains two amino acids involved in catalyzing deacylation. This
      similarity may explain the high beta-lactamase activity of wild-type PBP 5.
      Because of the low rate of deacylation of the G105D mutant, visualization of
      peptide substrates bound to the active site may be possible.

PMID- 10967104
TI  - Using a phage display library to identify basic residues in A-Raf required to
      mediate binding to the Src homology 2 domains of the p85 subunit of
      phosphatidylinositol 3'-kinase.
AB  - Src homology 2 (SH2) domains are found in a variety of cytoplasmic proteins
      involved in mediating signals from cell surface receptors to various
      intracellular pathways. They fold as modular units and are capable of recognizing
      and binding to short linear peptide sequences containing a phosphorylated
      tyrosine residue. Here we show that each of the SH2 domains of the p85 subunit of
      phosphatidylinositol 3-kinase selects phage displayed peptide sequences
      containing the core (L/I)-A-(R/K)-I-R. The serine/threonine kinase A-Raf,
      containing the sequence LQRIRS, is associated with the p85 protein in both
      quiescent and growth factor stimulated cells. This suggests that p85 and A-Raf
      exist in a protein complex in cells and that complex formation does not require
      growth factor stimulation. We also show that p85 and A-Raf can bind directly to
      each other in vitro and that this interaction is mediated in part by the p85 SH2
      domains. Further, the p85 SH2 domains require at least one of four distinct basic
      X-basic sequence motifs within A-Raf for binding. This is the first description
      of a phosphotyrosine-independent SH2 domain interaction that requires basic
      residues on the SH2 ligand.

PMID- 10967105
TI  - BAG1L enhances trans-activation function of the vitamin D receptor.
AB  - The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor
      superfamily of nuclear receptors that has potential tumor-suppressive functions.
      We show here that VDR interacts with and is regulated by BAG1L, a nuclear protein
      that binds heat shock 70-kDa (Hsp70) family molecular chaperones. Endogenous
      BAG1L can be co-immunoprecipitated with VDR from prostate cancer cells (ALVA31;
      LNCaP) in a ligand-dependent manner. BAG1L, but not shorter non-nuclear isoforms
      of this protein (BAG1; BAG1M/Rap46), markedly enhanced, in a ligand-dependent
      manner, the ability of VDR to trans-activate reporter gene plasmids containing a
      vitamin D response element in transient transfection assays. Mutant BAG1L lacking
      the C-terminal Hsc70-binding domain suppressed (in a concentration-dependent
      fashion) VDR-mediated trans-activation of vitamin D response element-containing
      reporter gene plasmids, without altering levels of VDR or endogenous BAG1L
      protein, suggesting that it operates as a trans-dominant inhibitor of BAG1L. Gene
      transfer-mediated elevations in BAG1L protein levels in a prostate cancer cell
      line (PC3), which is moderately responsive to VDR ligands, increased the ability
      of natural (1alpha,25(OH)(2) vitamin D(3)) and synthetic (1alpha, 25-dihydroxy-19
      nor-22(E)-vitamin D(3)) VDR ligands to induce expression of the VDR target gene,
      p21(Waf1), and suppress DNA synthesis. Thus, BAG1L is a direct regulator of VDR,
      which enhances its trans-activation function and improves tumor cell responses to
      growth-suppressive VDR ligands.

PMID- 10967106
TI  - Dominant negative MyD88 proteins inhibit interleukin-1beta /interferon-gamma 
      mediated induction of nuclear factor kappa B-dependent nitrite production and
      apoptosis in beta cells.
AB  - Insulin-dependent diabetes mellitus is an autoimmune disease in which pancreatic
      islet beta cells are destroyed by a combination of immunological and inflammatory
      mechanisms. In particular, cytokine-induced production of nitric oxide has been
      shown to correlate with beta cell apoptosis and/or inhibition of insulin
      secretion. In the present study, we investigated whether the interleukin (IL)
      1beta intracellular signal transduction pathway could be blocked by
      overexpression of dominant negative forms of the IL-1 receptor interacting
      protein MyD88. We show that overexpression of the Toll domain or the lpr mutant
      of MyD88 in betaTc-Tet cells decreased nuclear factor kappaB (NF-kappaB)
      activation upon IL-1beta and IL-1beta/interferon (IFN)-gamma stimulation.
      Inducible nitric oxide synthase mRNA accumulation and nitrite production, which
      required the simultaneous presence of IL-1beta and IFN-gamma, were also
      suppressed by approximately 70%, and these cells were more resistant to cytokine
      induced apoptosis as compared with parental cells. The decrease in glucose
      stimulated insulin secretion induced by IL-1beta and IFN-gamma was however not
      prevented. This was because these dysfunctions were induced by IFN-gamma alone,
      which decreased cellular insulin content and stimulated insulin exocytosis. These
      results demonstrate that IL-1beta is involved in inducible nitric oxide synthase
      gene expression and induction of apoptosis in mouse beta cells but does not
      contribute to impaired glucose-stimulated insulin secretion. Furthermore, our
      data show that IL-1beta cellular actions can be blocked by expression of MyD88
      dominant negative proteins and, finally, that cytokine-induced beta cell
      secretory dysfunctions are due to the action of IFN-gamma.

PMID- 10967107
TI  - Autoregulation and maturity onset diabetes of the young transcription factors
      control the human PAX4 promoter.
AB  - During pancreatic development, the paired homeodomain transcription factor PAX4
      is required for the differentiation of the insulin-producing beta cells and
      somatostatin-producing delta cells. To establish the position of PAX4 in the
      hierarchy of factors controlling islet cell development, we examined the control
      of the human PAX4 gene promoter. In both cell lines and transgenic animals, a 4.9
      kilobase pair region directly upstream of the human PAX4 gene transcriptional
      start site acts as a potent pancreas-specific promoter. Deletion mapping
      experiments demonstrate that a 118-base pair region lying approximately 1.9
      kilobase pairs upstream of the transcription start site is both necessary and
      sufficient to direct pancreas-specific expression. Serial deletions through this
      region reveal the presence of positive elements that bind several pancreatic
      transcription factors as follows: the POU homeodomain factor HNF1alpha, the
      orphan nuclear receptor HNF4alpha, the homeodomain factor PDX1, and a heterodimer
      composed of two basic helix-loop-helix factors. Interestingly, mutations in the
      genes encoding four of these factors cause a dominantly inherited form of human
      diabetes called Maturity Onset Diabetes of the Young. In addition, PAX4 itself
      has at least two high affinity binding sites within the promoter through which it
      exerts a strong negative autoregulatory effect. Together, these results suggest a
      model in which PAX4 expression is activated during pancreatic development by a
      combination of pancreas-specific factors but is then switched off once PAX4
      protein reaches sufficient levels.

PMID- 10967108
TI  - Topography of nicotinic acetylcholine receptor membrane-embedded domains.
AB  - The topography of nicotinic acetylcholine receptor (AChR) membrane-embedded
      domains and the relative affinity of lipids for these protein regions were
      studied using fluorescence methods. Intact Torpedo californica AChR protein and
      transmembrane peptides were derivatized with N-(1-pyrenyl)maleimide (PM),
      purified, and reconstituted into asolectin liposomes. Fluorescence mapped to
      proteolytic fragments consistent with PM labeling of cysteine residues in
      alphaM1, alphaM4, gammaM1, and gammaM4. The topography of the pyrene-labeled Cys
      residues with respect to the membrane and the apparent affinity for
      representative lipids were determined by differential fluorescence quenching with
      spin-labeled derivatives of fatty acids, phosphatidylcholine, and the steroids
      cholestane and androstane. Different spin label lipid analogs exhibit different
      selectivity for the whole AChR protein and its transmembrane domains. In all
      cases labeled residues were found to lie in a shallow position. For M4 segments,
      this is compatible with a linear alpha-helical structure, but not so for M1, for
      which "classical" models locate Cys residues at the center of the hydrophobic
      stretch. The transmembrane topography of M1 can be rationalized on the basis of
      the presence of a substantial amount of non-helical structure, and/or of kinks
      attributable to the occurrence of the evolutionarily conserved proline residues.
      The latter is a striking feature of M1 in the AChR and all members of the rapid
      ligand-gated ion channel superfamily.

PMID- 10967109
TI  - The binding of a glycoprotein 120 V3 loop peptide to HIV-1 neutralizing
      antibodies. Structural implications.
AB  - The structural and antigenic properties of a peptide ("CRK") derived from the V3
      loop of HIV-1 gp120 protein were studied using NMR and SPR techniques. The
      sequence of CRK corresponds to the central portion of the V3 loop containing the
      highly conserved "GPGR" residue sequence. Although the biological significance of
      this conserved sequence is unknown, the adoption of conserved secondary structure
      (type II beta-turn) in this region has been proposed. The tendency of CRK (while
      free or conjugated to protein), to adopt such structure and the influence of such
      structure upon CRK antigenicity were investigated by NMR and SPR, respectively.
      Regardless of conjugation, CRK is conformationally averaged in solution but a
      weak tendency of the CRK "GPGR" residues to adopt a beta-turn conformation was
      observed after conjugation. The influence of GPGR structure upon CRK antigenicity
      was investigated by measuring the affinities of two cognate antibodies: "5023A"
      and "5025A," for CRK, protein-conjugated CRK and gp120 protein. Each antibody
      bound to all the antigens with nearly the same affinity. From these data, it
      appears that: (a) antibody binding most likely involves an induced fit of the
      peptide and (b) the gp120 V3 loop is probably conformationally heterogeneous.
      Since 5023A and 5025A are HIV-1 neutralizing antibodies, neutralization in these
      cases appears to be independent of adopted GPGR beta-turn structure.

PMID- 10967110
TI  - Abl family kinases and Cbl cooperate with the Nck adaptor to modulate Xenopus
      development.
AB  - We previously showed that overexpression of the Nck Src homology (SH) 2/SH3
      adaptor in Xenopus embryos induced developmental defects including anterior
      truncation and mesoderm ventralization. Mutagenic analysis indicated that this
      was due to relocalization of endogenous proteins that bind the first two SH3
      domains of Nck. We therefore screened a Xenopus expression library with Nck SH3
      domains to identify Nck-interacting proteins, and evaluated candidate binding
      proteins for a potential role in Nck-induced anterior truncation/ventralization.
      Of 39 binding proteins analyzed, only the Abl-related kinase Arg and the Cbl
      proto-oncogene product bound preferentially to the first two SH3 domains in
      tandem compared with the individual domains, consistent with a role in the
      developmental phenotype. High level overexpression of c-Abl or Arg alone induced
      anterior truncation, as did lower levels of an activated form of Abl; Cbl alone
      had no effect. In a sensitized system where subthreshold amounts of a
      ventralizing Nck mutant were expressed, co-expression of the combination of Abl
      or Arg and Cbl at modest levels strongly potentiated anterior truncation, while
      Arg, Abl, or Cbl alone were without effect. These results suggest a role for both
      Cbl and Abl family kinases in patterning the Xenopus embryo.

PMID- 10967111
TI  - Synergistic adhesive interactions and signaling mechanisms operating between
      platelet glycoprotein Ib/IX and integrin alpha IIbbeta 3. Studies in human
      platelets ans transfected Chinese hamster ovary cells.
AB  - This study investigates three aspects of the adhesive interaction operating
      between platelet glycoprotein Ib/IX and integrin alpha(IIb)beta(3). These include
      the following: 1) examining the sufficiency of GPIb/IX and integrin
      alpha(IIb)beta(3) to mediate irreversible cell adhesion on immobilized von
      Willebrand factor (vWf) under flow; 2) the ability of the vWf-GPIb interaction to
      induce integrin alpha(IIb)beta(3) activation independent of endogenous platelet
      stimuli; and 3) the identification of key second messengers linking the vWf
      GPIb/IX interaction to integrin alpha(IIb)beta(3) activation. By using Chinese
      hamster ovary cells transfected with GPIb/IX and integrin alpha(IIb)beta(3), we
      demonstrate that these receptors are both necessary and sufficient to mediate
      irreversible cell adhesion under flow, wherein GPIb/IX mediates cell tethering
      and rolling on immobilized vWf, and integrin alpha(IIb)beta(3) mediates cell
      arrest. Moreover, we demonstrate direct signaling between GPIb/IX and integrin
      alpha(IIb)beta(3). Studies on human platelets demonstrated that vWf binding to
      GPIb/IX is able to induce integrin alpha(IIb)beta(3) activation independent of
      endogenous platelet stimuli under both static and physiological flow conditions
      (150-1800 s(-)(1)). Analysis of the key second messengers linking the vWf-GPIb
      interaction to integrin alpha(IIb)beta(3) activation demonstrated that the first
      step in the activation process involves calcium release from internal stores,
      whereas transmembrane calcium influx is a secondary event potentiating integrin
      alpha(IIb)beta(3) activation.

PMID- 10967112
TI  - Protection of human islets from the effects of interleukin-1beta by adenoviral
      gene transfer of an Ikappa B repressor.
AB  - Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that inhibits beta
      cell function and promotes Fas-triggered apoptosis. IL-1beta is thought to act
      early in the initiation of the autoimmune destruction of pancreatic beta cells in
      type I diabetes. IL-1beta promotes beta cell impairment, in part, by activating
      NF-kappaB transcription factor-dependent signaling pathways. We have examined
      whether beta cells could be protected from the effects of IL-1beta by
      overexpressing an inhibitor of NF-kappaB activity, IkappaB, by adenoviral gene
      transfer to intact human islets in culture. Infection of islets with an
      adenoviral vector encoding a non-phosphorylatable, non-degradable variant of
      IkappaBalpha resulted in normal insulin responses to glucose in the presence of
      IL-1beta. Furthermore, nitric oxide production was prevented and, more
      importantly, Fas-triggered apoptosis was inhibited following IkappaBalpha gene
      transfer. These results suggest that blocking the NF-kappaB pathway might prevent
      cytokine-induced beta cell impairment as a means of facilitating islet
      transplantation.

PMID- 10967113
TI  - Glucose down-regulates the expression of the peroxisome proliferator-activated
      receptor-alpha gene in the pancreatic beta -cell.
AB  - To better understand the action of glucose on fatty acid metabolism in the beta
      cell and the link between chronically elevated glucose or fatty acids and beta
      cell decompensation in adipogenic diabetes, we investigated whether glucose
      regulates peroxisomal proliferator-activated receptor (PPAR) gene expression in
      the beta-cell. Islets or INS(832/13) beta-cells exposed to high glucose show a 60
      80% reduction in PPARalpha mRNA expression. Oleate, either in the absence or
      presence of glucose, has no effect. The action of glucose is dose-dependent in
      the 6-20 mm range and maximal after 6 h. Glucose also causes quantitatively
      similar reductions in PPARalpha protein and DNA binding activity of this
      transcription factor. The effect of glucose is blocked by the glucokinase
      inhibitor mannoheptulose, is partially mimicked by 2-deoxyglucose, and is not
      blocked by the 3-O-methyl or the 6-deoxy analogues of the sugar that are not
      phosphorylated. Chronic elevated glucose reduces the expression levels of the
      PPAR target genes, uncoupling protein 2 and acyl-CoA oxidase, which are involved
      in fat oxidation and lipid detoxification. A 3-day exposure of INS-1 cells to
      elevated glucose results in a permanent rise in malonyl-CoA, the inhibition of
      fat oxidation, and the promotion of fatty acid esterification processes and
      causes elevated insulin secretion at low glucose. The results suggest that a
      reduction in PPARalpha gene expression together with a rise in malonyl-CoA plays
      a role in the coordinated adaptation of beta-cell glucose and lipid metabolism to
      hyperglycemia and may be implicated in the mechanism of beta-cell
      "glucolipotoxicity."

PMID- 10967114
TI  - Vascular endothelial growth factor up-regulation via p21-activated kinase-1
      signaling regulates heregulin-beta1-mediated angiogenesis.
AB  - Heregulin-beta1 promotes the activation of p21-activated kinase 1 (Pak1) and the
      motility and invasiveness of breast cancer cells. In this study, we identified
      vascular endothelial growth factor (VEGF) as a gene product induced by heregulin
      beta1. The stimulation by heregulin-beta1 of breast cancer epithelial cells
      induced the expression of the VEGF mRNA and protein and its promoter activity.
      Heregulin-beta1 also stimulated angiogenesis in a VEGF-dependent manner.
      Herceptin, an anti-HER2 antibody inhibited heregulin-beta1-mediated stimulation
      of both VEGF expression in epithelial cells and angiogenesis in endothelial
      cells. Because the activation of Pak1 and VEGF expression are positively
      regulated by heregulin-beta1, we hypothesized that Pak1 regulates VEGF
      expression, and hence explored the role of Pak1 in angiogenesis. We provide new
      evidence to implicate Pak1 signaling in VEGF expression. Overexpression of a
      kinase-dead K299R Pak1 leads to suppression of VEGF promoter activity, as well as
      VEGF mRNA expression and secretion of VEGF protein. Conversely, kinase-active
      T423E Pak1 promotes the expression and secretion of VEGF. Furthermore, expression
      of the heregulin-beta1 transgene, HRG, in harderian tumors in mice enhances the
      activation of Pak1 as well as expression of VEGF and angiogenic marker CD34
      antigen. These results suggest that heregulin-beta1 regulates angiogenesis via up
      regulation of VEGF expression and that Pak1 plays an important role in
      controlling VEGF expression and, consequently, VEGF secretion and function.

PMID- 10967115
TI  - Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1
      expression.
AB  - Integrins are transmembrane receptors involved in interactions between cells and
      extracellular matrix proteins. Here we show that cell adhesion regulates insulin
      receptor substrate-1 (IRS-1) mRNA synthesis. When fibroblasts are held in
      suspension, lower levels of IRS-1 mRNA, but not of IRS-2 mRNA, are detected, and
      this effect is due to the negative regulation of IRS-1 transcription rather than
      to decreased mRNA stability. Upon fibronectin- or vitronectin-mediated integrin
      stimulation, the level of IRS-1 mRNA was restored within 4 h. The focal adhesion
      kinase (FAK) is known to be activated upon integrin stimulation, and we found
      that IRS-1 was not expressed in FAK(-)(/-) cells. Stable re-expression of epitope
      tagged FAK in FAK(-)(/-) fibroblasts (DA2 cells) restored normal levels of IRS-1
      expression, confirming that IRS-1 mRNA expression is regulated by FAK. It is
      known that integrins activate the JNK pathway. However, in adherent FAK(-)(/-)
      cells, we failed to detect activation of JNK, whereas JNK was stimulated in DA2
      cells. This confirms the role of FAK in integrin-induced JNK stimulation. FAK
      independent stimulation of JNK with anisomycin treatment both in FAK(-)(/-) cells
      and in suspended FAK(+/+) cells confirmed that IRS-1 mRNA transcription can be
      partially regulated by JNK. We suggest that integrins can modulate insulin and
      insulin-like growth factor-1 signaling pathways by regulating the levels of IRS-1
      in cells and that FAK-mediated signaling to JNK is one pathway involved in this
      process.

PMID- 10967116
TI  - Activation of insulin signal transduction pathway and anti-diabetic activity of
      small molecule insulin receptor activators.
AB  - We recently described the identification of a non-peptidyl fungal metabolite (l
      783,281, compound 1), which induced activation of human insulin receptor (IR)
      tyrosine kinase and mediated insulin-like effects in cells, as well as decreased
      blood glucose levels in murine models of Type 2 diabetes (Zhang, B., Salituro,
      G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M. T. ,
      Pelaez, F., Ruby, C., Kendall, R. L., Mao, X., Griffin, P., Calaycay, J.,
      Zierath, J. R., Heck, J. V., Smith, R. G. & Moller, D. E. (1999) Science 284, 974
      977). Here we report the characterization of an active analog (compound 2) with
      enhanced IR kinase activation potency and selectivity over related receptors
      (insulin-like growth factor I receptor, epidermal growth factor receptor, and
      platelet-derived growth factor receptor). The IR activators stimulated tyrosine
      kinase activity of partially purified native IR and recombinant IR tyrosine
      kinase domain. Administration of the IR activators to mice was associated with
      increased IR tyrosine kinase activity in liver. In vivo oral treatment with
      compound 2 resulted in significant glucose lowering in several rodent models of
      diabetes. In db/db mice, oral administration of compound 2 elicited significant
      correction of hyperglycemia. In a streptozotocin-induced diabetic mouse model,
      compound 2 potentiated the glucose-lowering effect of insulin. In normal rats,
      compound 2 improved oral glucose tolerance with significant reduction in insulin
      release following glucose challenge. A structurally related inactive analog
      (compound 3) was not effective on insulin receptor activation or glucose lowering
      in db/db mice. Thus, small molecule IR activators exert insulin mimetic and
      sensitizing effects in cells and in animal models of diabetes. These results have
      implications for the future development of new therapies for diabetes mellitus.

PMID- 10967117
TI  - Cell cycle arrest and apoptosis induced by Notch1 in B cells.
AB  - Notch receptors play various roles for cell fate decisions in developing organs,
      although their functions at the cell level are poorly understood. Recently, we
      found that Notch1 and its ligand are each expressed in juxtaposed cell
      compartments in the follicles of the bursa of Fabricius, the central organ for
      chicken B cell development. To examine the function of Notch1 in B cells, a
      constitutively active form of chicken Notch1 was expressed in a chicken B cell
      line, DT40, by a Cre/loxP-mediated inducible expression system. Remarkably, the
      active Notch1 caused growth suppression of the cells, accompanied by a cell cycle
      inhibition at the G(1) phase and apoptosis. The expression of Hairy1, a gene
      product up-regulated by the Notch1 signaling, also induced the apoptosis, but no
      cell cycle inhibition. Thus, Notch1 signaling induces apoptosis of the B cells
      through Hairy1, and the G(1) cell cycle arrest through other pathways. This novel
      function of Notch1 may account for the recent observations indicating the
      selective inhibition of early B cell development in mice by Notch1.

PMID- 10967118
TI  - Inactivation of plasminogen activator inhibitor-1 by specific proteolysis with
      stromelysin-1 (MMP-3).
AB  - Matrix metalloproteinase-3 (MMP-3 or stromelysin-1) specifically hydrolyzes the
      Ser(337)-Ser(338) (P10-P9) and Val(341)-Ile(342) (P6-P5) peptide bonds in human
      plasminogen activator inhibitor-1 (PAI-1). Cleavage is completely abolished in
      the presence of the metal chelators EDTA or 1,10-phenanthroline. A stabilized
      active PAI-1 variant was also cleaved by MMP-3. At an enzyme/substrate ratio of
      1/10 at 37 degrees C, PAI-1 protein cleavage occurred with half-lives of 27 or 14
      min for active or stable PAI-1 and was associated with rapid loss of inhibitory
      activity toward tissue-type plasminogen activator with half-lives of 15 or 13
      min, respectively. A substrate-like variant of PAI-1, lacking inhibitory activity
      but with exposed reactive site loop, was cleaved with a half-life of 23 min,
      whereas latent PAI-1 in which a major part of the reactive site loop is inserted
      into the molecule, was resistant to cleavage. Biospecific interaction analysis
      indicated comparable binding of active, stable, and substrate PAI-1 to both
      proMMP-3 and MMP-3 (K(A) of 12-22 x 10(6) m(-1)), whereas binding of latent PAI-1
      occurred with lower affinity (1.7-2.3 x 10(6) m(-1)). Stable PAI-1 bound to
      vitronectin was cleaved and inactivated by MMP-3 in a manner comparable with that
      of free PAI-1; however, the cleaved protein did not bind to vitronectin. Cleavage
      and inactivation of PAI-1 by MMP-3 may thus constitute a mechanism decreasing the
      antiproteolytic activity of PAI-1 and impairing the potential inhibitory effect
      of vitronectin-bound PAI-1 on cell adhesion and/or migration.

PMID- 10967119
TI  - Regulation of gene expression by glucose in pancreatic beta -cells (MIN6) via
      insulin secretion and activation of phosphatidylinositol 3'-kinase.
AB  - Increases in glucose concentration control the transcription of the preproinsulin
      (PPI) gene and several other genes in the pancreatic islet beta-cell. Although
      recent data have demonstrated that secreted insulin may regulate the PPI gene
      (Leibiger, I. B., Leibiger, B., Moede, T., and Berggren, P. O. (1998) Mol. Cell
      1, 933-938), the role of insulin in the control of other beta-cell genes is
      unexplored. To study the importance of insulin secretion in the regulation of the
      PPI and liver-type pyruvate kinase (L-PK) genes by glucose, we have used
      intranuclear microinjection of promoter-luciferase constructs into MIN6 beta
      cells and photon-counting imaging. The activity of each promoter was increased
      either by 30 (versus 3) mm glucose or by 1-20 nm insulin. These effects of
      insulin were not due to enhanced glucose metabolism since culture with the
      hormone had no impact on the stimulation of increases in intracellular ATP
      concentration caused by 30 mm glucose. Furthermore, the islet-specific
      glucokinase promoter and cellular glucokinase immunoreactivity were unaffected by
      30 mm glucose or 20 nm insulin. Inhibition of insulin secretion with the Ca(2+)
      channel blocker verapamil, the ATP-sensitive K(+) channel opener diazoxide, or
      the alpha(2)-adrenergic agonist clonidine blocked the effects of glucose on L-PK
      gene transcription. Similarly, 30 mm glucose failed to induce the promoter after
      inhibition of phosphatidylinositol 3'-kinase activity with LY294002 and the
      expression of dominant negative-acting phosphatidylinositol 3'-kinase (Deltap85)
      or the phosphoinositide 3'-phosphatase PTEN (phosphatase and tensin homologue).
      LY294002 also diminished the activation of the L-PK gene caused by inhibition of
      5'-AMP-activated protein kinase with anti-5'-AMP-activated protein kinase alpha2
      antibodies. Conversely, stimulation of insulin secretion with 13 mm KCl or 10
      microm tolbutamide strongly activated the PPI and L-PK promoters. These data
      indicate that, in MIN6 beta-cells, stimulation of insulin secretion is important
      for the activation by glucose of L-PK as well as the PPI promoter, but does not
      cause increases in glucokinase gene expression or glucose metabolism.

PMID- 10967120
TI  - Hepatocyte nuclear factor 4alpha regulates the expression of pancreatic beta 
      cell genes implicated in glucose metabolism and nutrient-induced insulin
      secretion.
AB  - Mutations in the HNF4alpha gene are associated with the subtype 1 of maturity
      onset diabetes of the young (MODY1), which is characterized by impaired insulin
      secretory response to glucose in pancreatic beta-cells. Hepatocyte nuclear factor
      4alpha (HNF4alpha) is a transcription factor critical for liver development and
      hepatocyte-specific gene expression. However, the role of HNF4alpha in the
      regulation of pancreatic beta-cell gene expression and its correlation with
      metabolism secretion coupling have not been previously investigated. The
      tetracycline-inducible system was employed to achieve tightly controlled
      expression of both wild type (WT) and dominant-negative mutant (DN) of HNF4alpha
      in INS-1 cells. The induction of WT-HNF4alpha resulted in a left shift in glucose
      stimulated insulin secretion, whereas DN-HNF4alpha selectively impaired nutrient
      stimulated insulin release. Induction of DN-HNF4alpha also caused defective
      mitochondrial function substantiated by reduced [(14)C]pyruvate oxidation,
      attenuated substrate-evoked mitochondrial membrane hyperpolarization, and blunted
      nutrient-generated cellular ATP production. Quantitative evaluation of HNF4alpha
      regulated pancreatic beta-cell gene expression revealed altered mRNA levels of
      insulin, glucose transporter-2, L-pyruvate kinase, aldolase B, 2-oxoglutarate
      dehydrogenase E1 subunit, and mitochondrial uncoupling protein-2. The patterns of
      HNF4alpha-regulated gene expression are strikingly similar to that of its
      downstream transcription factor HNF1alpha. Indeed, HNF4alpha changed the
      HNF1alpha mRNA levels and HNF1alpha promoter luciferase activity through altered
      HNF4alpha binding. These results demonstrate the importance of HNF4alpha in beta
      cell metabolism-secretion coupling.

PMID- 10967121
TI  - Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I.
AB  - Nucleolin functions in ribosome biogenesis and contains an acidic N terminus that
      binds nuclear localization sequences. In previous work we showed that human
      nucleolin associates with the N-terminal region of human topoisomerase I (Top1).
      We have now mapped the topoisomerase I interaction domain of nucleolin to the N
      terminal 225 amino acids. We also show that the Saccharomyces cerevisiae
      nucleolin ortholog, Nsr1p, physically interacts with yeast topoisomerase I,
      yTop1p. Studies of isogenic NSR1(+) and Deltansr1 strains indicate that NSR1 is
      important in determining the cellular localization of yTop1p. Moreover, deletion
      of NSR1 reduces sensitivity to camptothecin, an antineoplastic topoisomerase I
      inhibitor. By contrast, Deltansr1 cells are hypersensitive to the topoisomerase
      II-targeting drug amsacrine. These findings indicate that nucleolin/Nsr1 is
      involved in the cellular localization of Top1 and that this localization may be
      important in determining sensitivity to drugs that target topoisomerases.

PMID- 10967122
TI  - Requirement of specific intrahelical interactions for stabilizing the inactive
      conformation of glycoprotein hormone receptors.
AB  - Systematic analysis of structural changes induced by activating mutations has
      been frequently utilized to study activation mechanisms of G-protein-coupled
      receptors (GPCRs). In the thyrotropin receptor and the lutropin receptor (LHR), a
      large number of naturally occurring mutations leading to constitutive receptor
      activation were identified. Saturating mutagenesis studies of a highly conserved
      Asp in the junction of the third intracellular loop and transmembrane domain 6
      suggested a participation of this anionic residue in a salt bridge stabilizing
      the inactive receptor conformation. However, substitution of all conserved
      cationic residues at the cytoplasmic receptor surface did not support this
      hypothesis. Asp/Glu residues are a common motif at the N-terminal ends of alpha
      helices terminating and stabilizing the helical structure (helix capping). Since
      Asp/Glu residues in the third intracellular loop/transmembrane domain 6 junction
      are not only preserved in glycoprotein hormone receptors but also in other GPCRs
      we speculated that this residue probably participates in an N-terminal helix
      capping structure. Poly-Ala stretches are known to form and stabilize alpha
      helices. Herein, we show that the function of the highly conserved Asp can be
      mimicked by poly-Ala substitutions in the LHR and thyrotropin receptor. CD and
      NMR studies of peptides derived from the juxtamembrane portion of the LHR
      confirmed the helix extension by the poly-Ala substitution and provided further
      evidence for an involvement of Asp in a helix-capping structure. Our data
      implicate that in addition to well established interhelical interactions the
      inactive conformation of GPCRs is also stabilized by specific intrahelical
      structures.

PMID- 10967123
TI  - The potentiation of estrogen on insulin-like growth factor I action in MCF-7
      human breast cancer cells includes cell cycle components.
AB  - To gain insight into the mechanisms involved in the cross-talk between IGF-1
      receptor (IGF-1R) and estrogen receptor signaling pathways, we used MCF-7-derived
      cells (SX13), which exhibit a 50% reduction in IGF-1R expression. Growth of NEO
      cells (control MCF-7 cells) was stimulated by both IGF-1 and estradiol (E2), and
      the addition of both mitogens resulted in a synergistic response. Estrogen
      enhanced IGF-1R signaling in NEO cells, but this effect was markedly diminished
      in SX13 cells. Estrogen was also able to potentiate the IGF-1 effect on the
      expression of cyclin D1 and cyclin E and on the phosphorylation of retinoblastoma
      protein in control but not in SX13 cells. IGF-1 increased the protein level of
      p21 and the luciferase activity of the p21 promoter, whereas it only reduced the
      protein level of p27 without affecting p27 promoter activity. Estrogen did not
      affect the p21 inhibitor, but it decreased the protein level of p27 and the p27
      promoter luciferase activity. These effects of both mitogens were also observed
      at the level of association of both cyclin-dependent kinase inhibitors with CDK2
      suggesting that IGF-1 and E2 affect the activity of both p21 and p27. Taken
      together, these data suggest that in MCF-7 cells, estrogen potentiates the IGF-1
      effect on IGF-1R signaling as well as on the cell cycle components. Moreover, IGF
      1 and E2 regulate the expression of p21 and p27 and their association with CDK2
      differently.

PMID- 10967124
TI  - A monomer-dimer equilibrium of a cellular prion protein (PrPC) not observed with
      recombinant PrP.
AB  - Both the purified normal (protease-sensitive) isoform of the prion protein
      (PrP(C)) (Pergami, P., Jaffe, H., and Safar, J. (1996) Anal. Biochem. 236, 63-73)
      and recombinant prion protein (PrP) have been found to be in monomeric form
      (Mehlhorn, I., Groth, D., Stockel, J., Moffat, B., Reilly, D., Yansura, D.,
      Willet, W. S., Baldwin, M., Fletterick, R., Cohen, F. E., Vandlen, R., Henner,
      D., and Prusiner, S. B. (1996) Biochemistry 35, 5528-5537; and this paper), and
      therefore PrP(C)-PrP(C) interactions were previously unknown. In this report we
      confirm recombinant PrP to be a monomer by analytical ultracentrifugation.
      However, by three lines of evidence (enzyme-linked immunosorbent assay (ELISA),
      cross-linking experiments, and size exclusion chromatography) we could also
      demonstrate that, under native conditions, at least part of the native bovine
      PrP(C) exists as a monomer-dimer equilibrium. A bovine PrP(C)-specific immuno
      sandwich ELISA was developed and calibrated with recombinant PrP (Meyer, R. K.,
      Oesch, B., Fatzer, R., Zurbriggen, A., and Vandevelde, M. (1999) J. Virol. 73,
      9386-9392). By this ELISA we identified a distinct PrP(C) fraction and partially
      purified this protein. When serial dilutions of brain homogenate or partially
      purified PrP(C) were measured, using the peptide antibody C15S, a nonlinear dose
      response curve was obtained. This nonlinearity was shown not to be due to an
      artifact of the procedure but to a monomer-dimer equilibrium of PrP(C) with
      preferential binding of the antibody to the dimer. From the curvature we could
      deduce the association constant (3.9 x 10(8) M(-1) at 37 degrees C). Accordingly,
      DeltaG degrees of the reaction was calculated (-48.6 kJ M(-1)), and DeltaH
      degrees (9.5 kJ M(-1)) as well as DeltaS degrees (0.2 kJ K(-1) M(-1)) were
      extrapolated from the van't Hoff plot. When serial dilutions of monomeric
      recombinant PrP were tested, only a straight line was obtained, supporting our
      hypothesis. Additional evidence of dimer formation was revealed by Western
      blotting of partially purified PrP(C) cross-linked by the homobifunctional cross
      linker BS(3). Finally, size exclusion chromatography of partially purified PrP(C)
      fractions revealed an additional shoulder not observed with recombinant PrP. The
      difference in respect of dimer formation between native PrP(C) and recombinant
      PrP could be explained by the lack of glycosylation of the latter.

PMID- 10967125
TI  - Oncogenic ras mediates apoptosis in response to protein kinase C inhibition
      through the generation of reactive oxygen species.
AB  - Ras is a well established modulator of apoptosis. Suppression of protein kinase C
      (PKC) activity can selectively induce apoptosis in cells expressing a
      constitutively activated Ras protein. We wished to determine whether reactive
      oxygen species serve as an effector of Ras-mediated apoptosis. Ras-transformed
      NIH/3T3 cells contained higher basal levels of intracellular H(2)O(2) compared
      with normal NIH/3T3 cells, and PKC inhibition up-regulated ROS to 5-fold greater
      levels in Ras-transformed cells than in normal cells. Treatment with N-acetyl-l
      cysteine reduced both the basal and inducible levels of intracellular H(2)O(2) in
      NIH/3T3-Ras cells and antagonized the induction of apoptosis by PKC inhibition.
      Culturing NIH/3T3-Ras cells in low oxygen conditions, which prevents ROS
      generation, also inhibited the apoptotic response to PKC inhibition. These
      results suggest that reactive oxygen species are necessary as downstream
      effectors of the Ras-mediated apoptotic response to PKC inhibition. However, the
      generation of ROS alone is not sufficient to induce apoptosis in Ras-transformed
      cells because inhibition of cell cycle progression prevented the induction of
      apoptosis in NIH/3T3-Ras cells without inhibiting the generation of intracellular
      H(2)O(2) observed after PKC inhibition. These findings suggest that continued
      cell cycle progression of Ras-transformed cells during PKC inhibition is also
      necessary for the induction of apoptosis.

PMID- 10967127
TI  - A mouse phenome project.
AB  - A community-wide effort to establish baseline phenotypic data on commonly used
      and genetically diverse inbred mouse strains and to provide the information
      through a publicly accessible database.

PMID- 10967126
TI  - Inhibition of NF-kappa B activation by arsenite through reaction with a critical
      cysteine in the activation loop of Ikappa B kinase.
AB  - Arsenite is a potent environmental toxin that causes various pathologies
      including cancers and skin disorders. Arsenite is believed to exert its
      biological effects through reaction with exposed sulfhydryl groups, especially
      pairs of adjacent thiols. Here, we describe the mechanism by which arsenite
      affects the NF-kappaB signaling pathway. Activation of transcription factor NF
      kappaB depends on the integrity of the IkappaB kinase (IKK) complex. We found
      that arsenite potently inhibits NF-kappaB and IKK activation by binding to Cys
      179 in the activation loop of the IKK catalytic subunits, IKKalpha/beta. The
      affinity of IKKbeta for trivalent arsenic was verified in vitro by the ability of
      IKKbeta to enhance the fluorescence of an arsenic-substituted fluorescein dye.
      The addition of 1,2-dithiol antidotes or replacement of Cys-179 with an alanine
      residue abolished dye binding to and arsenite inhibition of IKKbeta.
      Overexpression of IKKbeta (C179A) protects NF-kappaB from inhibition by arsenite,
      indicating that despite the involvement of a large number of distinct gene
      products in this activation pathway, the critical target for inhibition by
      arsenite is on the IKK catalytic subunits.

PMID- 10967129
TI  - Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmd(mdx) and
      Dmd(mdx3cv) dystrophin-deficient mice.
AB  - The SHIRPA protocol was proposed as a rapid, comprehensive screening method for
      qualitatively abnormal phenotypes in the mouse (Rogers et al., Mamm Genome 8,
      711, 1997). This screening technique is currently being used to identify mutants
      induced by N-ethylnitrosourea (ENU) mutagenesis (Brown and Nolan, Hum Mol Genet
      7, 1627, 1998). SHIRPA can be used to identify mutants with neuromuscular
      abnormalities, but the sensitivity of the protocol is unknown. We tested two
      dystrophin-deficient mutants Dmd(mdx) and Dmd(mdx3cv), both of which are
      indistinguishable from wild-type by a simple visual assessment, at different
      ages, using the primary screen of the SHIRPA protocol. The most dramatic
      observation was that both Dmd(mdx) and Dmd(mdx3cv) mice showed extreme fatigue
      after testing, while mice from the same C57BL strains appeared unaffected. Each
      strain of dystrophin-deficient mice showed a different profile in locomotor
      activity and deficiencies in the wire maneuver, righting reflex, and negative
      geotaxis tests. Furthermore, the wire maneuver test indicated an earlier onset of
      muscular impairment in Dmd(mdx) than Dmd(mdx3cv) mice. These data suggest that
      the SHIRPA primary screen is effective not only in identifying subtle
      neuromuscular mutants, but also in distinguishing qualitative differences between
      mutants with neuromuscular abnormalities.

PMID- 10967128
TI  - Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in
      upper gastrointestinal tract but significantly suppressed in human gastric cancer
      cells.
AB  - Amplification of proto-oncogenes associated with their over-expression is one of
      the critical carcinogenic events identified in human cancer cells. In many cases
      of human gastric cancer, a proto-oncogene ERBB-2 is co-amplified with CAB1 genes
      physically linked to ERBB-2, and both genes are over-expressed. The amplified
      region containing ERBB-2 and CAB1 was named 17q12 amplicon from its chromosomal
      location. The syntenic region corresponding to the 17q12 amplicon is well
      conserved in mouse. In this study we isolated and characterized a novel mouse
      gene that locates telomeric to the mouse syntenic region. Northern blot analysis
      using the mouse cDNA and a cloned partial cDNA of human homolog disclosed a
      unique expression pattern of the genes. They are expressed predominantly in the
      gastrointestinal (GI) tract and in the skin at a lower level. Moreover, in the GI
      tract, the expression is highly restricted to the esophagus and stomach. Thus, we
      named the mouse gene Gasdermin (Gsdm). This is the first report of a mammalian
      gene whose expression is restricted to both upper GI tract and skin.
      Interestingly, in spite of its expression in normal stomach, no transcript was
      detected by Northern blot analysis in human gastric cancer cells. These data
      suggest that the loss of the expression of the human homolog is required for the
      carcinogenesis of gastric tissue and that the gene has an activity adverse to
      malignant transformation of cells.

PMID- 10967130
TI  - Localization of 54 rat genes, and definition of new synteny groups conserved in
      the human and the rat.
AB  - In order to improve the rat gene map and comparative mapping with the human and
      the mouse, we determined the chromosome localization of 54 rat genes. Most genes
      encode transcription factors or other regulatory proteins of cancer relevance.
      The human homologs of four genes were also assigned to their respective
      chromosome. These data generated anchor points between the recently established
      radiation hybrid maps and the genetic and cytogenetic maps. They improve
      comparative mapping between the rat, the mouse, and the human gene maps, and in
      particular they disclose four new synteny groups conserved in the rat and the
      human. These new localizations should also be useful for the identification of
      genes involved in the control of quantitative traits such as cancer
      susceptibility or diabetes.

PMID- 10967131
TI  - Molecular analysis and chromosomal assignment of the canine CALC-I/alpha-CGRP
      gene.
AB  - We have isolated a recombinant phage harboring the canine CALC-I/alpha-CGRP gene.
      The gene spans a region of approx. 5.3 kb and consists of six exons with sizes
      ranging from 95 bp (exon 2) and 494 bp (exon 4). By alternative splicing, two
      transcripts with ORFs of 390 and 384 nt are generated. These encode either the 32
      amino acid-long hormone calcitonin (CALC) or the neurotransmitter calcitonin gene
      related peptide (alpha-CGRP) with a length of 37 amino acids after proteolytic
      processing of precursor molecules. The canine calcitonin precursor consists of
      130 amino acids with a molecular mass of 14.05 kDa and a statistical pI of 8.0,
      whereas the deduced alpha-CGRP precursor harbors 128 amino acids with a molecular
      mass of 13.87 kDa and a statistical pI of 8.6. Both polypeptides have a common N
      terminal region of 76 amino acids that is encoded by exons 2 and 3 and separated
      by different eight (CALC) or six (alpha-CGRP) amino acid spacers from the
      biologically active polypeptide. The CALC-I/alpha-CGRP gene is a member of the
      calcitonin gene family and was assigned to chromosome CFA 16q25.1. A comparative
      analysis of different dog breeds revealed a breed-specific allelic d(CAGGAG)
      hexanucleotide expansion in exon 3. This expansion results in an elongation of
      the common N-terminal region by two amino acids (glutamine-glutamic acid) and
      alters the molecular mass to 14.31 kDa (pI 7.9) and 14.13 kDa (pI 8.5) of the
      calcitonin and alpha-CGRP precursor, respectively.

PMID- 10967132
TI  - Isolation of DNA markers informative in purebred dog families by genomic
      representational difference analysis (gRDA).
AB  - Genomic Representational Difference Analysis (gRDA) is a subtractive DNA method
      to clone the differences between two related genomes, called tester and driver.
      We have evaluated this method to obtain polymorphic DNA markers for pedigree
      dogs. Amplified size-selected genomic restriction fragments (amplicons) of two
      dog littermates were repeatedly hybridized to each other in order to remove
      (subtract) those restriction fragments common to both sibs. Already after two
      rounds of subtractive hybridization, a clear enrichment of presumably tester
      specific restriction fragments was observed, which was even more pronounced after
      the third round of subtraction. A plasmid library of 3000 recombinant clones was
      constructed of the second round and of the third round difference product. DNA
      sequence determination of randomly chosen clones of each difference product
      showed that approximately 1000 unique clones were obtained in the second-round
      difference product and approximately 500 in the third-round difference product.
      About half of the clones identified in the second-round difference product were
      also present in the third-round difference product. Of the second-round
      difference product, 39 different gRDA fragments could be identified, of which 21
      were tester specific. In the third-round difference product, 22 different gRDA
      fragments were identified, of which 18 were tester specific. There were 13
      fragments in common, resulting in a total of 48 different fragments. In order to
      establish the localization of these markers, we performed mapping using the dog
      radiation hybrid panel RHDF5000. Of 39 mapped clones, 29 were mapped to 20
      existing RH groups, and 10 remained unlinked. It is concluded that gRDA is
      suitable to generate DNA markers to track disease genes within lines of pedigree
      dogs.

PMID- 10967133
TI  - Assignment of 60 human ESTs in cattle.
AB  - As part of the human genome study, large-scale cDNA sequencing has produced
      thousands of Expressed Sequence Tags (ESTs). Genethon has mapped in human 10,000
      of these ESTs and has shown that the primers of about 1000 ESTs could amplify
      bovine DNA. In this work, we have analyzed 233 primer pairs provided by Genethon,
      to assign type I sequences to the bovine genome by using a hamster-bovine somatic
      cell hybrid panel. Among these 233 primer pairs, 109 gave a specific PCR product
      with bovine genomic DNA, but for 50% the size of the PCR product was the same in
      cattle and hamster, requiring SSCP analysis. Finally, 60 ESTs were assigned to
      the bovine genome, and among them 46 were found on the bovine chromosome expected
      from heterologous painting data between cattle and human.

PMID- 10967134
TI  - Complete nucleotide sequence and genomic structure of the human NRAMP1 gene
      region on chromosome region 2q35.
AB  - Several lines of independent evidence suggest that human Natural Resistance
      Associated Macrophage Protein 1 gene (NRAMP1) is an important regulator of
      susceptibility to infectious diseases caused by certain intracellular pathogens.
      Here, we report the nucleotide sequence of 32198 bp of genomic DNA overlapping
      NRAMP1 on chromosomal region 2q35. The NRAMP1 gene spans 13604 bp. The gene and
      its 5' genomic region are highly enriched for DNA repeat sequences. A second gene
      was identified in the immediate vicinity of NRAMP1 and was tentatively named
      Nuclear LIM Interactor-Interacting Factor (NLI-IF) by analogy to its closest
      ortholog. The human NLI-IF gene begins 4721 bp downstream of the NRAMP1 stop
      codon and is composed of seven exons varying in size from 57 bp to 1644 bp. The
      gene gives rise to a 2655-bp mRNA transcript that contains a 783-bp open reading
      frame. The predicted molecular weight of the 261-amino acid NLI-IF protein is
      29.2 kDa. Several putative gene regulatory elements were identified in the 5'
      upstream region of NLI-IF, including consensus binding sequences for Sp1, AP-2,
      NF-kappa B, and PU 1. The NLI-IF amino acid sequence has homology to proteins
      that have a high degree of homology with the NLI-interacting factor from Gallus
      gallus and are found in divergent species ranging from yeast to plants. NLI-IF is
      part of a human gene family encoding four related proteins of unknown function.
      Northern blot analysis of 15 different human tissues revealed a 2.6-kb NLI-IF
      mRNA that was ubiquitously expressed, but at varying levels. A second transcript
      with estimated size of 7 kb was expressed only in the placenta. Our data provide
      new sequence information about the NRAMP1 gene region that will be useful in the
      search for genetic variants causally involved in altered susceptibility to
      infectious diseases.

PMID- 10967135
TI  - Organization of the human synphilin-1 gene, a candidate for Parkinson's disease.
AB  - We have recently identified a protein we called synphilin-1, which interacts in
      vivo with alpha-synuclein. Mutations in alpha-synuclein cause familial
      Parkinson's disease (PD). Alpha-synuclein protein is present in the pathologic
      lesions of familial and sporadic PD, and diffuse Lewy body disease, indicating an
      important pathogenic role for alpha-synuclein. Here we describe the structure of
      the human synphilin-1 gene (SNCAIP). The open reading frame of this gene is
      contained within ten exons. We have designed primers to amplify each SNCAIP exon,
      so these primers can now be used to screen for mutations or polymorphisms in
      patients with Parkinson's disease or related diseases. We found a highly
      polymorphic GT repeat within intron 5 of SNCAIP, suitable for linkage analysis of
      families with PD. We have mapped SNCAIP locus to Chromosome (Chr) 5q23.1-23.3
      near markers WI-4673 and AFMB352XH5. In addition, using immunohistochemistry in
      human postmortem brain tissue, we found that synphilin-1 protein is present in
      neuropil, similar to alpha-synuclein protein. Because of its association with
      alpha-synuclein, synphilin-1 may be a candidate for involvement in Parkinson's
      disease or other related disorders.

PMID- 10967136
TI  - The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple
      cancers.
AB  - We previously identified ps20 protein as a secreted growth inhibitor and purified
      the protein from fetal rat prostate urogenital sinus mesenchymal cell conditioned
      medium. The rat cDNA was subsequently cloned, and ps20 was found to contain a WAP
      type four-disulfide core motif, indicating it may function as a protease
      inhibitor. We now report cloning and characterization of the mouse ps20 gene
      (designated Wfdc1), the human homolog cDNA, and the human gene (designated
      WFDC1). Both the mouse and human WFDC1 genes consist of seven exons and encode
      respective ps20 proteins sharing 79.1% identity and nearly identical WAP motifs
      in exon 2. The WFDC1 gene was mapped by FISH analysis to human Chromosome (Chr)
      16q24, an area of frequent loss of heterozygosity (LOH) previously identified in
      multiple cancers including prostate, breast, hepatocellular, and Wilms' tumor.
      Identification and characterization of the WFDC1 gene may aid in better
      understanding the potential role of this gene and ps20 in prostate biology and
      carcinogenesis.

PMID- 10967137
TI  - Fine linkage and physical mapping suggests cross-over suppression with a
      retroposon insertion at the npc1 mutation.
AB  - Mouse Niemann-Pick disease type C1 (npc1), formerly designated spm
      (sphingomyelinosis), is an autosomal recessive lipid storage disorder. We
      generated a high-resolution linkage map in the 2.24-cM npc1 critical region by
      typing eight polymorphic markers in 2322 meioses (948 of these were previously
      reported). A minimal set of overlapping yeast artificial chromosomes (YACs) had
      previously been assembled (Hsu and Erickson 2000). The YAC 313-B-8, which covered
      this whole region, has been used to construct cosmid libraries. Three cosmid
      contigs were built, and one of them contained the npc1 locus. Two (CA)(n)
      microsatellites were identified, and the one new one was characterized, from the
      YAC-derived cosmids. The most proximal cosmid contig overlaps with markers near
      twirler (Tw). Both the physical map and genetic linkage map have been integrated
      to study the recombination frequencies in this particular region of the mouse
      genome, and recombination suppression due to the heterozygous insertion of DNA
      was suggested.

PMID- 10967138
TI  - Identification and characterization of naturally occurring variants of the
      macrophage scavenger receptor (SR-A).
AB  - The scavenger receptor (SR) family comprises a group of cell surface proteins
      functionally defined by their ability to bind chemically modified lipoproteins.
      In macrophages, the class A Type I and Type II SRs (SR-AI/II) are thought to play
      a key role in adherence to and phagocytosis of infectious agents.
      Immunoprecipitation studies show that the rat anti-SR-AI/II monoclonal antibody
      2F8 detects the mature, trimeric form of the receptor expressed in peritoneal
      macrophages from A/J, but not from C57Bl/6J (B6) mice. Subsequent sequencing of
      cDNA and genomic clones indicates that SR-AI and AII of A/J and B6 mice differ in
      sequence at nine positions, two in the cytoplasmic domain and seven in the
      extracellular spacer and alpha-helical coiled coil domains. These sequence
      polymorphisms are non-conservative and produce distinct receptor molecules that
      differ by four charged residues and alter recognition of the receptor by the
      monoclonal 2F8 antibody. The B6 SR-AI/II haplotype appears unique, since most
      inbred strains analyzed show the A/J-type haplotype. Interestingly, several of
      the B6 polymorphic variant residues are conserved in human and bovine receptors,
      suggesting a recent divergence of the A/J haplotype. Initial studies in CHO
      derived cells expressing individual receptor isoforms indicate that the A/J and
      B6 receptors are stable and can mature into oligomers expressed in the membrane
      fractions of these cells. In these transfectants, no major functional differences
      were detected between receptors of the two haplotypes with respect to
      internalization and degradation of (125)I-labeled acetylated LDL. However, since
      SR-AI/II recognizes a large number of structurally unrelated anionic molecules,
      the possibility that different haplotypes may affect either binding and release
      of other ligands, or receptor recycling, cannot be excluded.

PMID- 10967139
TI  - The genomic structure of c14orf1 is conserved across eukarya.
AB  - We have recently cloned the gene C14orf1, which is strongly expressed in normal
      testis and in several cancer cell lines and tumors. This gene maps to 14q24.3 and
      is interrupted by four introns. Two of them are also represented in the open
      reading frame of Schizosaccharomyces pombe in the same phase. In Arabidopsis
      taliana only the first of the two introns was found, in the same phase as the
      corresponding ones in S. pombe and human. Disruption of the ortholog in
      Saccharomyces cerevisiae (Yer044c) led to a severe growth defect, and C14orf1
      failed to complement mutant yeast when put under the control of the natural
      Yer044c promoter. Further studies are needed to understand the causes underlying
      the high degree of conservation of the C14orf1 genomic structure.

PMID- 10967140
TI  - Genetic comparison between laboratory rats and Japanese and German wild rats.

PMID- 10967141
TI  - A whole-genome radiation hybrid panel and framework map of the rat genome.

PMID- 10967142
TI  - Improvement of comparative map between porcine chromosomes 1 and 7 and human
      chromosomes 6, 14, and 15 by using human YACs.

PMID- 10967143
TI  - The X chromosome harbors quantitative trait loci for backfat thickness and
      intramuscular fat content in pigs.

PMID- 10967144
TI  - A horse whole-genome-radiation hybrid panel: chromosome 1 and 10 preliminary
      maps.

PMID- 10967145
TI  - Human chromosomes 3 and 21 are the products of an ancestral gene arrangement that
      is at least 300 million years old.

PMID- 10967146
TI  - Human NDUFS3 gene coding for the 30-kDa subunit of mitochondrial complex I:
      genomic organization and expression.

PMID- 10967147
TI  - A large-fragment porcine genomic library resource in a BAC vector.

PMID- 10967149
TI  - Clinical clues to the causes of large pericardial effusions.
AB  - PURPOSE: To examine whether the size of the effusion, the presence of tamponade,
      and inflammatory signs are useful in determining the causes of moderate or severe
      pericardial effusions. SUBJECTS AND METHODS: All echocardiograms performed at a
      general hospital between January 1990 and April 1996 were screened for
      pericardial effusion. Patients with moderate (echo-free space of 10 to 20 mm
      during diastole) or severe (echo-free space >20 mm) effusions were studied.
      RESULTS: We identified 322 patients (166 [52%] men, mean [+/- SD] age 56 +/- 17
      years [range 15 to 88 years]), 132 (41%) with moderate and 190 (59%) with severe
      pericardial effusion. The most frequent etiologic diagnoses were acute idiopathic
      pericarditis (n = 66 [20%]), iatrogenic effusions (n = 50 [16%]), cancer (n = 43
      [13%]), and chronic idiopathic pericardial effusion (n = 29 [9%]). In 192 (60%)
      of the patients, the cause of the effusion was a known medical condition. In the
      130 other patients, inflammatory signs were associated with acute idiopathic
      pericarditis (likelihood ratio = 5. 4, P < 0.001), severe effusions without
      inflammatory signs or tamponade were associated with chronic idiopathic
      pericardial effusion (likelihood ratio = 20, P < 0.001), and tamponade without
      inflammatory signs was associated with malignant effusions (likelihood ratio =
      2.9, P < 0.01). CONCLUSIONS: In many patients, pericardial effusions are due to a
      known underlying disease or condition. In patients without underlying diseases,
      inflammatory signs, the size of effusion, and the presence or absence of cardiac
      tamponade can be helpful in establishing cause.

PMID- 10967148
TI  - Incidence and preventability of adverse drug events in nursing homes.
AB  - PURPOSE: Adverse drug events, especially those that may have been preventable,
      are among the most serious concerns about medication use in nursing homes. We
      studied the incidence and preventability of adverse drug events and potential
      adverse drug events in nursing homes. METHODS: We performed a cohort study of all
      long-term care residents of 18 community-based nursing homes in Massachusetts
      during a 12-month observation period. Potential drug-related incidents were
      detected by stimulated self-report by nursing home staff and by periodic review
      of the records of nursing home residents by trained nurse and pharmacist
      investigators. Each incident was classified by 2 independent physician-reviewers,
      using a structured implicit review process, by whether or not it constituted an
      adverse drug event or potential adverse drug event (those that may have caused
      harm, but did not because of chance or because they were detected), by the
      severity of the event (significant, serious, life-threatening, or fatal), and by
      whether it was preventable. Examples of significant events included nonurticarial
      rashes, falls without associated fracture, hemorrhage not requiring transfusion
      or hospitalization, and oversedation; examples of serious events included
      urticaria, falls with fracture, hemorrhage requiring transfusion or
      hospitalization, and delirium. RESULTS: During 28,839 nursing home resident
      months of observation in the 18 participating nursing homes, 546 adverse drug
      events (1.89 per 100 resident-months) and 188 potential adverse drug events (0.65
      per 100 resident-months) were identified. Of the adverse drug events, 1 was
      fatal, 31 (6%) were life-threatening, 206 (38%) were serious, and 308 (56%) were
      significant. Overall, 51% of the adverse drug events were judged to be
      preventable, including 171 (72%) of the 238 fatal, life-threatening, or serious
      events and 105 (34%) of the 308 significant events (P < 0.001). Errors resulting
      in preventable adverse drug events occurred most often at the stages of ordering
      and monitoring; errors in transcription, dispensing, and administration were less
      commonly identified. Psychoactive medications (antipsychotics, antidepressants,
      and sedatives/hypnotics) and anticoagulants were the most common medications
      associated with preventable adverse drug events. Neuropsychiatric events were the
      most common types of preventable adverse drug events. CONCLUSIONS: Adverse drug
      events are common and often preventable in nursing homes. More serious adverse
      drug events are more likely to be preventable. Prevention strategies should
      target the ordering and monitoring stages of pharmaceutical care.

PMID- 10967150
TI  - A controlled trial of the health benefits of regular walking on a golf course.
AB  - PURPOSE: To study the effects of regular walking during a golf game on various
      health and fitness indicators in middle-aged men. METHODS: Study subjects were 55
      healthy male golfers aged 48 to 64 years who had been sedentary during the 7
      months before the study, and 55 age-matched, similarly sedentary controls. During
      the 20-week study, those in the intervention group were encouraged to play golf
      two to three times a week; the controls were not. Measurements of body
      composition, cardiorespiratory performance, motor and musculoskeletal fitness,
      blood pressure, and serum lipid, glucose, and insulin levels were obtained at
      baseline and after the 20-week study. RESULTS: Walking during a golf game was a
      practical and safe form of physical activity with high adherence. It
      significantly increased aerobic performance and trunk muscle endurance, with a
      net difference (pretraining to posttraining change between the golfers and
      controls) of 36 seconds (95% confidence interval [CI]: 19 to 53 seconds, P <
      0.001) for treadmill walking time and 13 seconds (95% CI: 2 to 24 seconds, P =
      0.02) for static back extension. In addition, regular walking favorably affected
      body composition, including reductions in weight of 1.4 kg (95% CI: 0.6 to 2.1
      kg, P < 0.001), in waist circumference of 2.2 cm (95% CI: 1.0 to 3.3 cm, P <
      0.001), and in abdominal skin fold thickness of 2.2 cm (95% CI: 0.9 to 3.4 cm, P
      = 0.001). Golfers also had significantly greater increases in serum high-density
      lipoprotein (HDL) cholesterol levels and in the ratio of HDL cholesterol to total
      cholesterol. CONCLUSIONS: Regular walking had many positive effects on the health
      and fitness of sedentary middle-aged men. Walking during a golf game is
      characterized by high adherence and low risk of injury and is therefore a good
      form of health-enhancing physical activity.

PMID- 10967151
TI  - Ischemic hepatitis: clinical presentation and pathogenesis.
AB  - BACKGROUND: The pathophysiology of ischemic hepatitis, otherwise known as "shock
      liver," is poorly understood, although it is believed to be the result of a
      reduction in systemic blood flow as typically occurs in shock. The aim of this
      study was to investigate the importance of this phenomenon as well as other
      clinical features in patients with ischemic hepatitis. METHODS: We identified a
      cohort of 31 patients (case group) who met the most commonly accepted definition
      of ischemic hepatitis (an acute reversible elevation in either the serum alanine
      or aspartate aminotransferase level of at least 20 times the upper limit of
      normal, excluding known causes of acute hepatitis or hepatocellular injury, in an
      appropriate clinical setting). We also evaluated the clinical features and serum
      aminotransferase levels in a cohort (the control group) of 31 previously healthy
      patients who sustained major nonhepatic trauma at San Francisco General Hospital,
      a major trauma center. Both groups of patients had documented systolic blood
      pressures <75 mm Hg for at least 15 minutes. Clinical and hemodynamic (invasive
      and noninvasive) data were recorded. RESULTS: Despite the marked reduction in
      blood pressure, no patient in the control group developed ischemic hepatitis. The
      mean (+/- SD) peak serum aspartate aminotransferase level in the control group
      was only 78 +/- 72 IU, in contrast with a mean peak of 2,088 +/- 2,165 IU in the
      case group. All 31 patients with ischemic hepatitis had evidence of underlying
      organic heart disease, 29 (94%) of whom had right-sided heart failure.
      CONCLUSIONS: Systemic hypotension or shock alone did not lead to ischemic
      hepatitis in any patient. The vast majority of patients with ischemic hepatitis
      had severe underlying cardiac disease that had often led to passive congestion of
      the liver. These data lead us to propose that right-sided heart failure, with
      resultant hepatic venous congestion, may predispose the liver to hepatic injury
      induced by a hypotensive event.

PMID- 10967152
TI  - Effects of adding a leukotriene antagonist or a long-acting beta(2)-agonist in
      asthmatic patients with the glycine-16 beta(2)-adrenoceptor genotype.
AB  - PURPOSE: In the United Kingdom, about 40% of patients with asthma are homozygous
      for the glycine-16 beta(2)-adrenoceptor polymorphism, which predisposes them to
      agonist-induced down-regulation and desensitization of the beta(2)-adrenoceptor.
      We assessed the effects of adding treatment with either a long-acting beta(2)
      agonist (inhaled formoterol, 12 microg twice daily) or a leukotriene receptor
      antagonist (oral zafirlukast, 20 mg twice daily) to inhaled corticosteroid
      therapy in patients with this genotype. SUBJECTS AND METHODS: We enrolled 24
      patients with mild to moderate asthma who were being treated with inhaled
      corticosteroids. Patients were randomly assigned to receive one of three
      treatments (placebo, zafirlukast, or formoterol in addition to inhaled
      corticosteroids) for 1 week each in a crossover fashion, separated by a 1-week
      placebo run-in and washout period. Measurements of bronchoprotection (measured as
      the provocative dose of methacholine that produced a 20% decline in forced
      expiratory volume in 1 second [FEV(1)]), exhaled nitric oxide (a surrogate marker
      of airway inflammation), and symptoms were made before each treatment and 12
      hours after the last dose of each treatment. RESULTS: Both formoterol and
      zafirlukast were equally effective in maintaining asthma control compared with
      placebo: the geometric mean-fold difference in the methacholine provocative dose
      was 1.5-fold (95% confidence interval [CI]: 1.1- to 2.2-fold) for zafirlukast and
      1.9-fold (95% CI: 1.2- to 2.9-fold) for formoterol. As compared with placebo,
      zafirlukast caused a significant suppression in exhaled nitric oxide (1.7-fold
      difference in geometric mean values, 95% CI: 1.1- to 2.6-fold) but formoterol did
      not (1.2-fold difference, 95% CI: 0.8- to 1.9-fold). Diary cards showed
      significant (P <0.05) improvements in the peak flow with formoterol (morning and
      evening) and zafirlukast (evening) as compared with placebo. CONCLUSIONS:
      Formoterol and zafirlukast maintained asthma control in patients who might be
      genetically predisposed to fare worse with long-acting beta(2)-agonists. The
      reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti
      inflammatory effects in addition to those seen with inhaled corticosteroids.

PMID- 10967153
TI  - How many deaths occur annually from adverse drug reactions in the United States?
AB  - PURPOSE: The numbers of deaths attributed to adverse drug reactions by death
      certificates and by the Food and Drug Administration's (FDA) spontaneous
      postmarketing surveillance system (MedWatch) were compared in order to
      characterize national mortality statistics. METHODS: Mortality statistics related
      to adverse drug reactions were obtained from national public-use databases of
      death certificates based on appropriate International Classification of Disease
      (ICD-9) codes and from MedWatch during 1995. The number of deaths, frequency
      distributions of sex and age groups, and rankings of drug categories associated
      with adverse reactions were compared. RESULTS: During 1995, 206 deaths were
      attributed to adverse drug reactions on death certificates in the United States,
      whereas MedWatch tabulated 6,894 fatalities. The proportions of men and women
      were similar, and the majority of deaths involved persons 60 years of age and
      older, in both data sets. The rankings of drug categories associated with adverse
      drug reactions differed in the two data sets. CONCLUSION: The numbers of deaths
      reported in these data sets varied 34-fold and were up to several 100-fold less
      than values based on extrapolations of surveillance programs. These differences
      indicate that better and more comprehensive data are needed to develop
      appropriate health care policies to improve drug safety.

PMID- 10967154
TI  - The fate of manuscripts rejected by a general medical journal.
AB  - PURPOSE: The fate of research manuscripts that have been rejected by medical
      journals is of interest to authors, editors, and peer reviewers, but previous
      studies were conducted before the widespread availability of computerized
      literature searches. We update the previous investigations of the fate of
      rejected research manuscripts by using an electronic literature search and a
      larger sample, a longer follow-up, and more descriptive journal indexes. METHODS:
      Using a retrospective cohort study design, we examined 350 manuscripts rejected
      by the Annals of Internal Medicine, a general medical journal, during 1993 and
      1994. We assessed the number of manuscripts that were published after initial
      rejection, time to eventual publication, journal type (general versus specialty),
      and journal impact factor (higher scores indicated greater impact) and immediacy
      index. RESULTS: Of 350 rejected manuscripts, 240 (69%, 95% confidence interval
      [CI]: 64% to 73%) were eventually published after a mean of 552 days (95% CI: 479
      to 544 days, range 121 to 1, 792 days). Of 226 rejected research articles and
      reviews, 159 (70%, 95% CI: 64% to 76%) were subsequently published in specialty
      journals. During 1993 and 1994, the mean impact factor for articles published in
      the Annals was 9.60 (95% CI: 9.56 to 9.64), compared with a mean of 3.09 (95% CI:
      2.80 to 3.37) for the journals in which the rejected articles were subsequently
      published (mean difference 6. 52, 95% CI: 6.24 to 6.81, P < 0.0001). The
      immediacy index was also lower for these journals. Time to publication had a weak
      negative correlation with the impact factor of the journal in which the article
      was published (correlation coefficient -0.15, P = 0.007). CONCLUSIONS: The
      majority of the manuscripts that were rejected from a large general medical
      journal were eventually published after an average of 18 months. Most were
      published in specialty journals with lower impact factor and immediacy index
      ratings.

PMID- 10967155
TI  - Patient-oriented research: principles and new approaches to training.
AB  - Remarkable advances in modern biology have enhanced our understanding of disease,
      permitting us to define-and potentially to treat-illness at the cellular and
      molecular level. The challenge we now face as physicians and physician-scientists
      is ensuring that these advances find expression in clinical practice. Thus far,
      the distance from the bench to the bedside has been surprisingly difficult to
      span, reflecting the need to develop broader, more integrative approaches to
      understanding how component molecules and physiologic systems function in the
      context of the whole person. Although there appears to be a consensus about the
      need to pursue such integrative, patient-oriented research, a mechanism for
      training future investigators in this discipline is less well established. In
      this essay, we present and develop the rationale for a set of underlying
      principles for patient-oriented research that can be used to guide appropriate
      training in this field. We also describe briefly a recently established prototype
      program-the Harvard initiative in Patient-Associated Science: Training,
      Education, Understanding, and Research (PASTEUR)-that we hope will help cultivate
      patient-oriented investigators and catalyze the evolution of patient-oriented
      research into a fully realized academic discipline.

PMID- 10967156
TI  - A clinical update in polycythemia vera and essential thrombocythemia.
AB  - Polycythemia vera and essential thrombocythemia pose specific management issues
      that distinguish them from other chronic myeloproliferative disorders. They are
      associated with a better prognosis, as well as a variable risk of
      thrombohemorrhagic complications. In addition, essential thrombocythemia occurs
      comparatively more often in young people and women. Treatment strategies for
      patients with polycythemia vera and essential thrombocythemia must consider the
      possibility of long-term survival, morbidity from thrombotic complications,
      transformation into myelofibrosis with myeloid metaplasia or acute myeloid
      leukemia, and the effect of specific therapies on the incidence of leukemic
      transformation and on pregnancy. There is increasing concern about the possible
      leukemogenic effect of hydroxyurea. Newer therapeutic agents, including
      interferon alpha and anagrelide, are being used more often. Ongoing studies are
      reexamining the effects of low-dose aspirin in preventing thrombotic
      complications.

PMID- 10967158
TI  - A drive for the health benefits of walking.

PMID- 10967157
TI  - Nitric oxide and intestinal inflammation.
AB  - Inflammation of the intestinal tract remains a very serious concern in the
      clinical setting. Unfortunately, to date, the mechanisms underlying many
      inflammatory conditions such as sepsis or inflammatory bowel diseases are poorly
      understood and our therapeutic interventions are less than ideal. Over the past
      decade, an abundance of research has been directed toward the role of nitric
      oxide (NO) in intestinal inflammation. It has become apparent that NO might have
      a dichotomous role as both a beneficial and detrimental molecule. Nitric oxide is
      a weak radical produced from L-arginine via the enzyme nitric oxide synthase
      (NOS). NOS exists in three distinct isoforms; constitutively (cNOS) expressed
      neuronal NOS (NOS1 or nNOS) and endothelial NOS (NOS3 or eNOS) or an inducible
      isoform (NOS2 or iNOS) capable of high production output of NO during
      inflammation. Constitutively expressed NOS has been shown to be critical to
      normal physiology and inhibition of these enzymes (nNOS or eNOS) caused damage.
      It has been proposed that the high output production of NO from iNOS causes
      injury, perhaps through the generation of potent radicals such as peroxynitrite
      and hence may explain the apparent dichotomous role of NO. However, recent
      studies have challenged this simple paradigm providing evidence that iNOS may
      have some protective role in some inflammatory models. Moreover, the importance
      of peroxynitrite has been questioned. In this review we discuss the role of cNOS
      and iNOS in intestinal inflammation and provide an overview of peroxynitrite in
      intestinal inflammation, highlighting some of the controversy that exists.

PMID- 10967159
TI  - The fate of rejected manuscripts.

PMID- 10967160
TI  - Patient-oriented research: definitions and new paradigms.

PMID- 10967161
TI  - Adverse drug events and near misses: who's counting?

PMID- 10967162
TI  - Pericardial effusion: a continuing drain on our diagnostic acumen.

PMID- 10967163
TI  - Supporting research in departments of internal medicine: recommendations for NIH.

PMID- 10967164
TI  - Pregnancy outcome in renal transplant recipients.
AB  - OBJECTIVE: To correlate pregnancy outcome with complications in pregnancy and
      transplantation-to-pregnancy interval in renal transplant recipients in Croatia.
      METHOD: Data on 23 pregnancies after prepregnancy stabilization of blood pressure
      and normalization of graft function were retrospectively analyzed. RESULT: The
      mean interval between transplantation and conception was 3.1 years. Primary renal
      disease was chronic glomerulonephritis in 7, chronic pyelonephritis in 7 and
      agenesis of right kidney and stenosis of left renal artery in 1 patient. There
      were 10 term and 5 preterm deliveries, 6 induced and 2 spontaneous abortions. The
      mean gestational age was 38.1 weeks and the mean newborn birthweight was 3015 g.
      The prematurity rate was 21.7%. Patients with arterial hypertension in pregnancy,
      elevated serum creatinine level and bacteriuria, as well as those with conception
      occurring less than 2 years after transplantation, had a higher rate of
      therapeutic and spontaneous abortions, preterm deliveries and low birth weight
      infants. CONCLUSION: The interval between transplantation and conception, as well
      as allograft function during pregnancy, seem to be of great importance for
      successful obstetric outcome in renal transplant patients.

PMID- 10967165
TI  - Prevalence and risk factors for hepatitis C virus (HCV) infection among pregnant
      Brazilian women.
AB  - OBJECTIVES: To determine the prevalence and the risk factors associated with HCV
      infection among women at childbirth, and to assess potential for infectivity of
      anti-HCV-positive women. METHODS: A total of 6995 women were interviewed and
      screened for HCV antibodies. Association and logistic regression analyses were
      conducted. RESULTS: The anti-HCV prevalence was 1.5% by EIA-3 and 0.8% by RIBA-3;
      HCV-RNA (RT-PCR) was detected in 74% of the RIBA-positive samples. Blood
      transfusion, race (blacks), alcohol abuse, a history of STD and anti-HBc
      positivity were independent risk factors for HCV positivity. Except for
      parenteral exposure, independent predictors of anti-HCV were a history of STD,
      anti-HBc positivity, a sex partner with multiple sex partners and a sex partner
      with a history of hepatitis. CONCLUSIONS: The prevalence of anti-HCV is higher in
      pregnant women than in blood donors. Sexual exposure may facilitate the spread of
      HCV and there is a high potential for mother-to-infant transmission.

PMID- 10967166
TI  - Risk factors for pre-eclampsia in an Asian population.
AB  - OBJECTIVE: To identify the risk factors for pre-eclampsia in an Asian population.
      METHOD: We conducted a retrospective cohort study involving 29375 Taiwanese women
      who delivered between July 1990 and September 1998, excluding pregnancies
      complicated by chronic hypertension or fetal malformations. RESULT: Four hundred
      and fifteen women had pre-eclampsia (1.4%). Women who had a history of pre
      eclampsia (OR 6.3, 95% CI 4.4, 9.2), multiple gestation (OR 3.6, 95% CI 2.4,
      5.5), a prepregnancy BMI > 24.2 kg/m(2) (OR 2.4, 95% CI 1. 8, 3.1), were > 34
      years of age (OR 1.8, 95% CI 1.4, 2.4), nulliparous (OR 1.3, 95% CI 1.2, 1.5),
      had urinary tract infection (OR 4.8, 95% CI 1.5, 15.8), or worked during
      pregnancy (OR 1.9, 95% CI 1.4, 2.4) were at increased risk of pre-eclampsia.
      CONCLUSION: Some of the risk factors for pre-eclampsia among Asian women are the
      same as those of other ethnic groups, whereas some of the risk factors are
      different.

PMID- 10967167
TI  - Assessment of gestational age based on ultrasonic femur length after the first
      trimester: a simple mathematical correlation between gestational age (GA) and
      femur length (FL).
AB  - OBJECTIVE: The ultrasonic measurement of the fetal femur length is a sensitive
      and precise variable for estimation of fetal growth and development. The
      objective of this study was to predict gestational age in fetuses more than 13
      weeks of gestation by ultrasound measurement of the femur length. METHOD: In this
      study, pregnant mothers were identified by the criteria of normalities such as:
      well-known LMP, regular menstrual cycles, no use of OCP for the last 3 months, no
      smoking, no history of diabetes, etc. RESULT: The relation between gestational
      age and fetal femur length has been determined by cross-sectional analysis of 900
      normal fetuses (> or = 14 weeks of gestation) using real time ultrasonography.
      Mathematical modeling of the data has demonstrated that the femur growth curve is
      non-linear beyond 13 weeks of gestation. With the aid of a scientific calculator
      the data were analyzed and a simple second grade equation has been derived: GA
      (weeks) = 0.262(2) FL (cm) + 2 FL + 11.5, S.D. approximately +/- 5
      days(Honarvar's Formula 3). With the use of this data, the error in the
      estimation of GA given as FL is +/-5 days. CONCLUSION: This simple, new and
      accurate equation appears to be clinically reliable and easy to use and suggests
      that previous normal ultrasonic fetal femur length curves for another population
      may under- or overestimate normal fetal age for the Iranian population. Thus, our
      formula is an excellent means of estimating true gestational age.

PMID- 10967168
TI  - Bacterial vaginosis and contraceptive methods.
AB  - OBJECTIVES The aim of this study was to investigate if bacterial vaginosis is
      associated with the use of specific contraceptives. METHODS: The study population
      consisted of 1314 women attending for periodical preventive examinations at our
      gynecology unit at the II Institute of Obstetrics and Gynecology of the
      University 'La Sapienza' in Rome. The patient's history and any current genital
      symptom were recorded on a structured protocol. Current users of contraceptives
      were compared with non-users. The chi(2) test and the t-test were used in the
      statistical analysis; a stepwise logistic regression analysis was performed to
      assess the simultaneous effect of more than one variable and to identify for
      possible confounding factors. RESULTS: Both oral contraceptive and condom use
      showed a significant protective effect against bacterial vaginosis. Our results
      also showed a significant increase of BV among IUD users, either before or after
      adjustments. CONCLUSIONS: This study showed a significant negative association
      between BV and OC and condom use, respectively, and a significant positive
      association between BV and IUD use. Therefore, we suggest that it is advisable to
      carry out a systematic microscopic evaluation in order to identify BV for IUD
      users.

PMID- 10967169
TI  - GnRH agonist decreases endothelial nitric oxide synthase (eNOS) expression in
      leiomyoma.
AB  - OBJECTIVES To define the effect of GnRH agonist (GnRHa) treatment on endothelial
      nitric oxide synthase (eNOS) expression in leiomyoma. As eNOS expression is more
      pronounced in leiomyoma compared to parental myometrium, we hypothesized that the
      mechanism(s) of tumor shrinkage by GnRHa may be due to decreased nitric oxide
      (NO) production in leiomyoma. METHODS: Eleven patients with leiomyoma were
      operated for myoma enucleation by laparatomy. Six of them were treated with GnRHa
      every 28 days, three times before the operation. The remaining five patients who
      had no treatment prior to operation formed the control group. Blood was drawn
      from the patients before treatment and on the day of operation for the assay of
      serum estradiol (E(2)). Immunohistochemical localization of eNOS expression in
      leiomyoma and myometrium in treated patients, and in leiomyoma in the control
      group, was performed using monoclonal antibodies specific to eNOS. RESULTS: All
      treated subjects showed a significant reduction of fibroid volume at the end of
      therapy. eNOS-positive cells were localized primarily within the vascular
      endothelium and smooth muscle cells, but had weak expression in fibroid and
      myometrial muscle cells in the treated group. The immunoreactivity was similar
      for both the leiomyoma and myometrium (P > 0.05). In contrast to this, the
      control group had shown strong expression in leiomyoma muscle cells (P < 0.005)
      in addition to the vascular endothelium and smooth muscle cells. CONCLUSION:
      GnRHa-induced tumor shrinkage should be due to diminished eNOS expression, most
      probably by lowering estrogen secretion.

PMID- 10967170
TI  - Clinical classification of vesicouterine fistula.
AB  - OBJECTIVE AND METHODSs: The aim of this paper is to propose a classification of
      vesicouterine fistula based on the routes of menstrual flow. RESULTS: Three types
      of the fistula are distinguished: type I - with menouria; type II - with dual
      flow via both the bladder and vagina; and type III - with normal vaginal menses.
      CONCLUSIONS: There is relevance of such division to both diagnosis and treatment.
      The simplicity and clinical utility of this classification warrant its widespread
      use.

PMID- 10967171
TI  - Attitudes, management and consequences of nausea and vomiting of pregnancy in the
      United States and Canada.
AB  - BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects a large proportion of
      pregnant women. In 1983, Bendectin((R)), the only FDA-approved drug for NVP, was
      removed from the market by its manufacturer due to legal costs based on claims of
      teratogenicity, which were subsequently proven to be unsubstantiated. In Canada,
      a generic form of Bendectin (Diclectin; a doxylamine/pyridoxine combination) has
      continued to be available, with increasing use over the last few years.
      OBJECTIVE: To characterize the attitudes, management and consequences of NVP
      among pregnant women in the USA, where no approved drug for NVP is available, and
      in Canada, where such a drug is available. DESIGN: Prospective, observational
      study. RESULTS: Women suffering from NVP (N = 1444) were interviewed, of which
      42% were American and 58% were Canadian. The two groups had similar maternal
      characteristics and a similar distribution of severity of NVP, although among
      Canadian women the NVP continued for slightly longer. American respondents were
      treated significantly more often by an obstetrician as their primary caregiver,
      were more commonly advised by their caregiver to change their diet and/or
      lifestyle and to use non-pharmacological agents to manage their NVP, and more
      often perceived anti-emetics as posing an increased risk for malformations (all P
      < 0.001). Canadian respondents reported a family physician as their primary
      caregiver significantly more often, were more commonly advised to take anti
      emetic medications and perceived their NVP as causing a concern to their unborn
      (all P < 0.001). American women experienced significantly larger weight loss,
      more hospitalizations and more time lost from paid work. CONCLUSIONS: Lack of an
      approved drug for symptoms of NVP may be associated with unwarranted and
      preventable adverse health effects. Because this is an observational study, these
      associations do not necessarily prove causation.

PMID- 10967172
TI  - The potential of midwives providing primary obstetric care to reduce perinatal
      deaths in a rural region.
AB  - OBJECTIVE: To determine the proportion of perinatal deaths that could be reduced
      by midwives providing primary obstetric services. METHOD: The study was conducted
      in a rural region of the Eastern Cape, South Africa. The primary obstetric and
      final causes of perinatal deaths and avoidable factors related to these deaths
      were determined in a large town and two small towns. RESULTS: In the three towns
      52 (48.6%) of the 107 avoidable factors were related to medical care while 20
      (38.5%) of these had the potential to be prevented at the level of care rendered
      by midwives. In the large town 21 (20.6%) of 102 and in the smaller towns 15
      (24.6%) of 61 perinatal deaths had potential for intervention by midwives.
      CONCLUSION: The 22.1% of perinatal deaths potentially preventable by midwives
      presupposes complete patient cooperation within an optimally functioning health
      system.

PMID- 10967173
TI  - Simplified disposable abdominal and vulvar drapes for cesarean section in
      maternal HIV-1 infection.

PMID- 10967174
TI  - Incarcerated pregnant uterus in an incisional hernia.

PMID- 10967175
TI  - Effects of community and health facility interventions on postpartum hemorrhage.

PMID- 10967176
TI  - Law and ethics in conflict over confidentiality?
AB  - Ethical principles that require the preservation of patients' confidential
      information are reinforced by principles found in several areas of law, such as
      law on contracts, negligence, defamation and fiduciary duty. However, laws
      sometimes compel disclosures of medical confidences, and more often may justify
      or excuse disclosures. Legally contentious issues concern patients' confidences
      regarding possible unlawful conduct, such as pregnancy termination, and the risk
      of spread of HIV and other infections. This article reviews the various legal
      bases of the duty of confidentiality, and legal challenges to the ethical
      obligation of non-disclosure. It addresses the justifications and limits of
      exchange of patients' health information among healthcare professionals and
      trainees, and considers legally recognized limits of confidential duties, and the
      scope of legitimate disclosure. An underlying theme is how to determine whether
      physicians are ethically justified in employing the discretion the law sometimes
      affords them to breach patients' expectations of confidentiality.

PMID- 10967177
TI  - Update on the pathophysiology of the epilepsies.
AB  - The pathophysiology of convulsive and non-convulsive epilepsies is discussed in
      its primary generalised forms. Focal, clinical and experimental epilepsies, with
      emphasis placed on the temporal lobe epilepsies (TLE) and their pathophysiologies
      are also reviewed. Neurotransmitters and neuromodulators and between them, the
      second messenger systems are considered in the generation, maintenance or
      inhibition of the epileptic discharge. Action mechanisms of the more classic
      antiepileptic drugs are briefly summarized along with the therapeutic strategies
      that might achieve the final control of abnormal discharges, including genetic
      control as a promising alternative in the current state of research. We
      emphasized the study of all type of glutamate and GABA receptors and their
      relation with mRNA editing in the brain. Some of the genetic studies which have
      been so fruitful during the last ten years and which have brought new insights
      regarding the understanding of epileptic syndromes are summarized in this
      article.

PMID- 10967178
TI  - A nonlinear biomathematical model for the study of intracranial aneurysms.
AB  - The formation and rupture of aneurysms is a significant medical problem, but is
      not clearly understood. Most intracranial aneurysm are located in the circle of
      Willis. We consider a nonlinear mathematical model that simulates the blood flow
      inside the aneurysm, one of the relevant factors in the evolution of an aneurysm.
      Different techniques from nonlinear analysis are used in order to obtain, from
      the model, several consequences that would help to understand some medical
      aspects of aneurysms of the circle of Willis.

PMID- 10967180
TI  - Habituation of cutaneomuscular reflexes recorded from the first dorsal
      interosseous and triceps muscle in man.
AB  - Cutaneomuscular reflexes have been recorded from the first dorsal interosseous
      muscle during a sustained abduction of the index finger of 20 subjects (25
      recordings) following stimulation of the digital nerves at the following
      frequencies: 2 Hz, 3 Hz, 5 Hz, 7 Hz and 9 Hz, presented in random order. Five
      hundred stimuli were given at each frequency. EMG was rectified and consecutive
      batches of 100 sweeps of each set of 500 responses were averaged time locked to
      the stimulus. All reflex components, E1, I1 and E2, exhibit habituation with the
      E1 component habituating the most and the I1 component the least. There was
      considerable variation in the rate of habituation between subjects. The rate of
      habituation was independent of the frequency of stimulation. Reflex responses
      were recorded from the triceps brachii muscle in eight subjects; this reflex
      response habituated at a faster rate than the E2 component recorded from the
      first dorsal interosseous muscle. These results are discussed in relation to the
      choice of stimulus parameters for the clinical testing of cutaneous reflexes. We
      conclude that it is important to consistently average the same number of
      responses.

PMID- 10967179
TI  - Flow cytometric differentiation of Asian and Western types of multiple sclerosis,
      HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and
      hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK
      cell subsets.
AB  - We examined the alterations of memory CD4(+) T cell subsets bearing surface
      receptors linked to either Th1 or Th2 cytokine production as well as natural
      killer (NK) cell subsets by three color flow cytometry in the peripheral blood
      from 36 patients with clinically definite multiple sclerosis (MS), 27 patients
      with HAM/TSP, 13 patients with hyperIgEaemic myelitis who had mite antigen
      specific IgE and 25 healthy controls (HC). The patients with MS were clinically
      classified into an optico-spinal form of MS (Asian type, MS-A) and the
      conventional form of MS (Western type, MS-W). MS-A showed a significant increase
      of CD4(+)CD45RA(-)CCR5(+) cells (Th1 cells) through the relapse and remission
      phases in comparison to HC, while MS-W showed a significant increase of
      CD4(+)CD45RO(+)CD62L(-) cells (Th1 cells) only at the relapse phase. HAM/TSP
      showed a significant increase of CCR5(+) and CD62L(-) memory CD4(+) T cells as
      well as CD30(+) memory CD4(+) T cells (Th2 cells) in comparison to HC. On the
      other hand, a selective increase of CD4(+)CD45RO(+)CD30(+) cells was found in
      hyperIgEaemic myelitis. The percentage of mature NK cells (CD3(-)CD16(+)CD56(+)
      cells) as well as double negative T cells (CD3(+)CD4(-)CD8(-) cells) decreased
      significantly in HAM/TSP in comparison to HC. Our findings therefore suggest a
      flow cytometric analysis of Th1/Th2-associated markers on memory CD4(+) T cells
      as well as NK cell subsets to be useful for differentiating various inflammatory
      neurologic conditions.

PMID- 10967181
TI  - Transcranial doppler sonography-ergometer test for the non-invasive assessment of
      cerebrovascular autoregulation in humans.
AB  - Cerebrovascular hemodynamics during physical stress have been sparsely
      investigated, mostly through risky invasive techniques. The aim of this study was
      to determine the effect of ergometer stress on cerebrovascular hemodynamics in
      humans using the non-invasive and thus clinically-applicable method of
      transcranial Doppler sonography (TCD) combined with simultaneous non-invasive
      measurements of cardiovascular parameters. In eighteen healthy subjects (six
      women, twelve men; 29.3+/-4.6 years old) left midcerebral artery blood flow
      velocities (CBFVs) were continuously monitored using TCD during 3 min at rest, 3
      min during ergometry and 3 min recovery. Simultaneously, systolic, diastolic,
      mean CBFVs, pulsatility index (PI), heart rate, beat-to-beat blood pressure (BP)
      and transcutaneous p(CO(2)) were measured. The subjects were supine with elevated
      trunk. Ergometry was performed by pedalling a Muhe-ergometer. In eight
      volunteers, the procedure was repeated within the next day to test the
      repeatability of the results. Heart rate increased significantly during ergometry
      (from 65.2+/-11 to 105. 3+/-12.3/min; P<0.05). The systolic BP increased
      significantly slightly later during ergometry (from 118.9+/-8.6 to 141.6+17.9
      mmHg; P<0.05). Transcutaneous p(CO(2)) was initially within physiological ranges,
      but increased significantly after a delay during the 3rd min of cycling (from
      39.7+/-3.7 to 41.1+/-4.7 mmHg; P<0.05). MFV started to rise significantly after 1
      min of the exercise period (from 59.6+10.9 to 68.3+13.9 cm/s; P<0.05). PI
      increased immediately and significantly at the start of exercise (PI at rest
      0.93+0.11; PI ergometry 1.1+0.13; P<0.05). The results were found to be
      reproducible in the eight volunteers. The cerebrovascular changes during
      ergometer exercise may reflect the combined activation of the cerebrovascular
      autoregulative mechanisms (neurogenic, myogenic and metabolic). The TCD-ergometer
      test presented here is non-invasive and would seem to present a low risk for
      patients who are judged fit enough for mild exercise. The test may contribute to
      the detection of cerebrovascular abnormalities in various diseases.

PMID- 10967182
TI  - Widespread expression of alpha-synuclein and tau immunoreactivity in Hallervorden
      Spatz syndrome with protracted clinical course.
AB  - Hallervorden-Spatz syndrome (HSS) is a rare autosomal recessive disorder
      clinically characterized by extrapyramidal signs and progressive dementia. In a
      typical case, the clinical symptoms become apparent during late childhood, and
      usually the course is protracted over a decade or more. We recently had an
      opportunity to study the brains of two cases of HSS with a clinical course of
      over 30 years. Case 1 was a 44-year-old female and case 2 was a 37-year-old male.
      Grossly, the brains showed severe fronto-temporal lobar atrophy with abundant
      spheroids and mild iron deposits in the globus pallidus, associated with features
      of motor neuron disease. In addition, there was diffuse sponginess in the
      atrophic cortex as well as widespread Alzheimer's neurofibrillary tangles (NFTs)
      and Lewy bodies (LBs) in the cortical and subcortical regions, including the
      spinal cord. Ultrastructurally, NFTs were composed of paired helical filaments,
      and LBs of central dense cores with radiating fibrils. Discrete immunostaining
      was demonstrated in NFTs and neuropil threads with various antibodies against
      phosphorylated tau, and in LBs with antibody against alpha-synuclein. In
      addition, diffuse, overlapping immunoreactivity of alpha-synuclein and
      phosphorylated tau was seen within the cytoplasm of many neurons. However, when
      LBs and NFTs coexisted within the same neurons, they were clearly segregated. The
      findings of our present cases as well as those reported in the literature may
      indicate that simultaneous and extensive occurrence of abnormal phosphorylation
      of tau and accumulation of alpha-synuclein may constitute cardinal pathological
      features of HSS with protracted clinical course.

PMID- 10967183
TI  - Familial spinal arachnoiditis with secondary syringomyelia: clinical studies and
      MRI findings.
AB  - We report the clinical and MRI findings of two patients with familial spinal
      arachnoiditis. Although their initial symptoms were various, they both showed
      spastic paraparesis and sensory disturbance below the thoracic level. Cytokines
      and WBC in the CSF were studied, but they were not elevated at all. The spinal
      magnetic resonance images of each showed extensive arachnoiditis and a cystic
      structure. The other impressive features included: (i) an enhancement within the
      thickened arachnoid and an adhesion between the spinal cord and the dura mater,
      (ii) deformation of the thoracic cord where the arachnoid adhered, and (iii)
      secondary syrinx formation. Laminectomy may have an adverse outcome for such
      patients.

PMID- 10967184
TI  - Vitamin D receptor gene polymorphism in multiple sclerosis and the association
      with HLA class II alleles.
AB  - We have previously reported that the association between Bsm I polymorphism, one
      of the vitamin D receptor genes (VDRG) polymorphism, and multiple sclerosis (MS).
      In this report, we investigated the further possible role or relevance of VDRG in
      the pathogenesis of MS. Apa I polymorphism was detected by PCR-RFLP from the DNA
      of 77 conventional MS patients and 95 healthy controls. The study of the Bsm I
      and Apa I haplotypes was carried out by employing previously reported Bsm I data.
      The AA genotype and the [A] allele in the profiles were significantly more
      prevalent in MS patients than in controls (P=0.0070 and P=0.0321, respectively).
      In the [A] allele-positive MS patients, the positive rate of DPB1*0501 in HLA was
      significantly higher than that of the [A] allele-positive controls and that of
      the [A] allele-negative MS patients even when the corrected P value (P(corr)) was
      applied (P(corr)=0.0220 and P(corr)=0.0077, respectively). The frequency of
      DRB1*1501 was higher in the [A] allele-positive patients than in the [A] allele
      positive controls and the [A] allele-negative patients (P(uncorr)=0.0431 and
      P(uncorr)=0.0089, respectively), but the P values did not reach statistical
      significance after P corrections. The rate of Bsm I and Apa I haplotypes was much
      higher in bA/bA-positive MS patients than in the controls (P=0.0003), and in the
      bA positive MS patients, the positive rate of DPB1*0501 was higher than that of
      the bA-positive controls and that of the bA-negative MS patients (P(corr)=0.0308
      and P(corr)=0.0033, respectively). These results indicate that VDRG polymorphism
      may be associated with susceptibility to MS, and HLA alleles may correlate with
      risk for MS together with VDRG.

PMID- 10967186
TI  - The influence of surface roughness on porcelain strength.
AB  - OBJECTIVES: In order to adjust occlusion, the functional surfaces of porcelain
      restorations are often ground and mechanical machining is even an essential part
      of the CAD-CAM process for these restorations. The aim of this study was to
      investigate the influence of the finishing procedures on the biaxial flexure
      strength of four commercial porcelains. METHODS: Four commercial porcelains of
      which two are used for metal-ceramic restorations (Flexo Ceram Dentine and Vita
      VM K68) and two for veneers and inlays (Duceram LFC Dentine and Cerinate BODY)
      are used in this study. For each porcelain, sixty discs (O = 22 mm, h = +/- 2.0
      mm) were produced using twelve different finishing procedures. Twenty discs were
      left untreated, twenty discs were milled, using a high-speed diamond disc, and
      twenty discs were machined in a high-speed grinding/polishing device. Half of the
      samples were glazed. In each of these six groups, half of the samples were stored
      for 16 h at 80 degrees C in a 4% acetic acid solution. The biaxial flexure
      strength was determined using the ball-on-ring method. In each group the
      roughness of the surface was determined and examined via SEM. RESULTS: With the
      exception of Flexo Ceram Dentine, a significant correlation was found between the
      roughness of the surface and the biaxial strength: the smoother the surface, the
      stronger the sample. The differences in biaxial strength may be attributed to the
      stress concentration of an applied load due to the roughness of the surface
      caused by mechanical finishing or chemical action. The fact that the strength of
      Flexo Ceram Dentine was not affected by the different surface treatments is
      probably due to the size of the leucite particles, which apparently induce more
      stress concentration than the surface flaws and the roughness of the surface.
      SIGNIFICANCE: It was concluded that surface roughness determines the strength of
      a porcelain material, except where the inner structure of the material causes
      greater stress concentration than that caused by the combination of surface
      roughness and surface flaws.

PMID- 10967185
TI  - Immunohistochemical markers for intracranial ependymoma recurrence. An analysis
      of 88 cases.
AB  - Intracranial ependymomas are the third most common primary brain tumor in
      children. Although clinical and histological criteria for ependymoma prognosis
      are recognized, studies have reported contradictory results. Prognostic
      significance based on immunohistochemistry of ependymomas has been reported in a
      few studies. Eighty-eight patients with intracranial ependymomas were examined
      retrospectively for immunoexpression of various tumor-associated antigens and
      apoptosis. The results demonstrated significant preponderance of expression of
      the tenascin, vascular endothelial growth factor protein (VEGF), epidermal growth
      factor (EGFR), and p53 protein in high-grade tumors. Also high-grade ependymomas
      revealed more prominent labeling indices (LI) for proliferative marker Ki-S1 and
      lower LI for cyclin-dependent kinase inhibitor p27/Kip1. For low-grade
      ependymomas the progression free survival time (PFS) was found to be
      significantly shorter for Ki-S1 LI>/=5%, and for tenascin, VEGF, and EGFR
      positivity. For high-grade ependymomas PFS was found to be significantly reduced
      for age <16 years, subtotal tumor removal, p27 LI <20%, p53 positivity, and for
      apoptotic index (AI) <1%. The classification regression tree analysis exhibited
      four groups of ependymomas; (1) low-grade tenascin negative (32 cases, recurrence
      rate=0), (2) high-grade with AI >/=1% (21 cases, recurrence rate=57%), (3) low
      grade tenascin-positive (10 cases, recurrence rate=89%), and (4) high-grade with
      AI <1% (25 cases, recurrence rate=100%). So, the immunohistochemical variables
      were found to be strongest predictors of ependymoma recurrence and they seem to
      be useful for assessing individual tumor prognosis in routinely processed biopsy
      specimen.

PMID- 10967187
TI  - Comparison of two heat-pressed all-ceramic dental materials.
AB  - OBJECTIVES: The processing route for two heat-pressed all-ceramic materials
      (Empress and OPC) is virtually identical. The purpose of this study was to
      determine the mechanical properties of both materials and determine if
      significant differences exist between them. METHODS: X-ray powder diffraction of
      the ceramics before and after processing was carried out to identify the crystal
      phases present. The mechanical properties of both materials were tested.
      Specimens were tested for hardness, fracture toughness (indentation method) and
      flexural strength (biaxial method). The results were statistically evaluated and
      tested for differences using a Mann-Whitney test. Secondary electron imaging of
      both materials was carried out before and after processing. RESULTS: X-ray powder
      diffraction revealed that OPC changes as a result of heat-pressing from being a
      complex mixture of crystalline oxides to a glass-ceramic. In contrast Empress is
      a glass-ceramic before and after processing. X-ray diffraction identified leucite
      as the main crystalline phase in both ceramics. The biaxial flexural strength of
      OPC was 153.6 (17.8) MPa and for Empress was 134.4 (11.5) MPa. The hardness of
      OPC was 7.28 (0.62) GPa and for Empress was 6.94 (0.79) GPa. Indentation fracture
      toughness of OPC was 1.36 (0.29) MPam0.5 and for Empress was 1.33 (0.08) MPam0.5.
      Secondary electron images show Empress to be the same before and after processing
      while OPC is clearly very different. Empress also appears to have a higher glass
      content compared with OPC. SIGNIFICANCE: The results of X-ray diffraction show
      that Empress is pre-cerammed whilst OPC is not. Statistical analysis revealed
      that no significant difference exists between the two materials for any of the
      mechanical properties tested at a 95% (p < 0.05) confidence level. It was
      concluded that no difference exists between the two materials on completion of
      processing.

PMID- 10967188
TI  - Novel priming and crosslinking systems for use with isocyanatomethacrylate dental
      adhesives.
AB  - OBJECTIVES: (a) to design, formulate and evaluate prototype primers and a
      crosslinking agent for use with isocyanatomethacrylate-based comonomer adhesives
      and (b) to establish correlations between bond strength and solubility parameter
      differences between the adhesives and etched dentin, and the permeability
      coefficients of the adhesives. METHODS: Equimolar mixtures of 2-isocyanatoethyl
      methacrylate (IEM) and a methacrylate comonomer were formulated with tri-n-butyl
      borane oxide (TBBO) as the free radical initiator to have cure times of 6-10 min.
      Shear bond strengths to dentin were determined for each adhesive mixture (n = 7)
      using standard testing protocols. Shear bond strengths for the three systems were
      also determined after application of "reactive primers" to the dentin surface.
      The "reactive primers" contained 10-20 parts by weight of the respective
      comonomer mixture and 3.5 parts by weight TBBO in acetone. Solubility parameters
      difference values (delta delta) and permeability coefficients (P) were
      approximated for each adhesive system and correlated with shear bond strength
      values. Additionally, a crosslinking agent was prepared by bulk reaction of an
      equimolar mixture containing IEM and a methacrylate comonomer. The effects of
      crosslinker addition on: (a) the setting time of IEM; and (b) the setting times
      and initiator requirements of selected IEM/comonomer mixtures were determined.
      RESULTS: Shear bond strength values (MPa): IEM/HEMA 13.6 +/- 2.0 (no primer),
      20.1 +/- 2.0 (with primer); IEM/HETMA 9.3 +/- 3.3 (no primer), 20.8 +/- 8.1 (with
      primer); IEM/AAEMA 13.6 +/- 1.9 (no primer), 17.3 +/- 3.2 (with primer). Also,
      approximated permeability coefficients showed a significant correlation (r =
      +0.867, p < 0.001) with shear bond strength values. Crosslinker addition studies
      with IEM/4-META: (a) at 5-9 mol% reduced the setting time of IEM polymerization
      by 79%; and (b) at 6 mol% reduced initiator level requirements 60-70% to achieve
      a comparable setting time, and decreased setting times by ca. 75% for a given
      initiator level with selected IEM/methacrylate adhesive systems. SIGNIFICANCE:
      The shear bond strengths of isocyanatomethacrylate-based dental adhesives can be
      enhanced by using reactive primers; their setting times and initiator
      requirements can be improved using a dimethacrylate crosslinker. Approximated
      permeability coefficients may be useful as indicators of bonding performance for
      dentin adhesive systems.

PMID- 10967190
TI  - Strain patterns in cervical enamel of teeth subjected to occlusal loading.
AB  - OBJECTIVES: This study was planned to investigate the variations in strains in
      enamel under different patterns of occlusal loading, using three-dimensional
      finite element analysis (3D FEA) and strain gage measurements in extracted teeth.
      METHODS: A 3D FEA model of a mandibular second premolar was used to investigate
      effects of occlusal load on enamel surface strains, particularly in response to
      oblique directions of cuspal loading. Point loads of 100 N were applied axially
      and at 45 degrees from the vertical on the buccal or lingual incline of the
      buccal cusp, either in the bucco-lingual plane or at varying mesio-distal
      angulations (up to +/- 20 degrees). Patterns of strain observed in the FEA model
      were confirmed experimentally using strain gages on extracted premolars mounted
      in a servohydraulic testing machine. RESULTS: Strains predicted from the FEA
      model were in excellent agreement with the strain gage measurements. Strains were
      concentrated near the cementoenamel junction (CEJ) regardless of load direction.
      A vertical load on the buccal cusp tip resulted in compressive strains on the
      buccal surface but small tensile strains in lingual cervical enamel. Strains
      resulting from oblique loads on buccal cusp inclines were complex and asymmetric,
      with either tension or compression occurring in any location depending on the
      site and angle of loading. SIGNIFICANCE: The magnitude, direction and character
      of strains in cervical enamel are highly dependent on patterns of loading. The
      asymmetric pattern of strains in buccal cervical enamel in response to oblique
      occlusal forces is consistent with the common clinical picture of asymmetric non
      carious cervical lesions.

PMID- 10967189
TI  - The effect of hybrid layer thickness on bond strength: demineralized dentin zone
      of the hybrid layer.
AB  - OBJECTIVES: The purpose of this study was to evaluate the correlation between
      hybrid layer thickness and bond strength using specimens acid-conditioned for
      varying lengths of time. METHODS: The dentin surfaces of human premolars,
      sectioned to remove the enamel from the labial surface, were conditioned with
      35.0% phosphoric acid of an adhesive resin system (Scotchbond Multi-Purpose; 3M)
      for 15 (as directed by the manufacturer), 60, 120, or 180 s (experimental acid
      conditioning times). The bonded specimens were then sectioned perpendicular to
      the adhesive interface to measure the hybrid layer thickness by SEM. The
      specimens for the micro-tensile test were sectioned perpendicular to the adhesive
      interface and trimmed to an hourglass-shape. Then, the micro-tensile test was
      performed at a crosshead speed of 1.0 mm/min. The bond strengths and hybrid layer
      thickness were statistically compared with Student's t-test (p < 0.05). All
      fractured surfaces were also observed by SEM. RESULTS: Significant differences
      between the groups exposed to acid for 15 and 60 s, and those exposed for 120 and
      180 s were observed in hybrid layer thickness and bond strength (p < 0.05). SEM
      observation of the fractured surfaces revealed that a demineralized dentin zone
      without resin impregnation remained within the hybrid layer. SIGNIFICANCE: A
      demineralized dentin zone was formed in the bond structures after prolonged acid
      conditioning, resulting in low bond strength. The shrinkage of the hybrid layer
      due to desiccation during the SEM examination process provided evidence of the
      presence of the demineralized dentin zone within the hybrid layer.

PMID- 10967191
TI  - Cutting efficiency of air-turbine burs on cast titanium and dental casting
      alloys.
AB  - OBJECTIVE: The purpose of this study was to investigate the cutting efficiency of
      air-turbine burs on cast free-machining titanium alloy (DT2F) and to compare the
      results with those for cast commercially pure (CP) Ti, Ti-6Al-4V alloy, and
      dental casting alloys. METHODS: The cast metal (DT2F, CP Ti, Ti-6Al-4V, Type IV
      gold alloy and Co-Cr alloy) specimens were cut with air-turbine burs (carbide
      burs and diamond points) at air pressures of 138 or 207 kPa and a cutting force
      of 0.784 N. The cutting efficiency of each bur was evaluated as volume loss
      calculated from the weight loss cut for 5 s and the density of each metal. The
      bulk microhardness was measured to correlate the machinability and the hardness
      of each metal. RESULTS: The amounts of DT2F cut with the carbide burs were
      significantly (p < 0.05) greater than for the other titanium specimens at either
      138 or 207 kPa. The diamond points exhibited similar machining efficiency among
      all metals except for Type IV gold alloy. The increase in the volume loss of Co
      Cr alloy (Vitallium) cut with the diamond points showed a negative value (-29%)
      with an increase in air pressure from 138 to 207 kPa. There was a negative
      correlation between the amounts of metal removed (volume loss) and the hardness
      (r2 = 0.689) when the carbide burs were used. SIGNIFICANCE: The results of this
      study indicated that a free-machining titanium alloy (DT2F) exhibited better
      machinability compared to CP Ti and Ti-6Al-4V alloy when using carbide fissure
      burs. When machining cast CP Ti and its alloys, carbide fissure burs possessed a
      greater machining efficiency than the diamond points and are recommended for
      titanium dental prostheses.

PMID- 10967192
TI  - Water-enhanced crystallization of leucite in dental porcelain.
AB  - OBJECTIVE: The purpose of this study was to determine whether long-term exposure
      of dental porcelain to saliva during temporary cementation of a porcelain-fused
      to-metal (PFM) restoration could enhance leucite crystallization if the
      restoration is refired. Such water-enhanced leucite crystallization in dental
      porcelains could lead to porcelain-metal thermal incompatibility problems.
      METHODS: Six commercial dental body porcelains and the Component No. 1 (leucite
      containing) frit of the Weinstein et al. [13] patent were studied. For each
      porcelain, 30 coupon specimens were randomly assigned to a treatment group. Ten
      specimens were placed in artificial saliva, 10 in distilled water, and 10 in a
      desiccator and were stored for six months. At the end of the six months, an
      additional 10 coupons of each porcelain were prepared to serve as a control. All
      40 specimens of each porcelain were randomized and subjected to one additional
      firing. Leucite weight fraction was determined by quantitative X-ray powder
      diffraction analysis via an internal standard technique. RESULTS: Comparisons
      among the treatments via the least-squares-means test-adjusting for porcelain
      showed that the saliva group mean leucite weight fraction was significantly
      higher than that of the other groups. The change in porcelain thermal expansion
      that would be associated with a leucite change in this range would be between 0.2
      x 10(-6) K-1 and 0.3 x 10(-6) K-1. SIGNIFICANCE: The results of this work
      constitute the first demonstration that moisture absorbed by a porcelain can act
      as a glass modifier and enhance the crystallization of the glass during
      subsequent firing. The effect was sufficiently large to generate thermal
      expansion changes that would exceed the maximum safe mismatch between porcelain
      and metal.

PMID- 10967193
TI  - Factors influencing pulpal response to cavity restorations.
AB  - OBJECTIVES: The purposes of this retrospective work were: (1) to determine the
      relative importance of bacteria on cavity walls, remaining dentin thickness and
      post-operative time on pulpal inflammation after cavity restoration; (2) to
      compare the respective influences of bacterial microleakage and the restorative
      material itself on pulp reaction severity. METHODS: 317 class V cavities, in
      human bicuspids scheduled for extraction for orthodontic reasons were used for
      this study. Nine different materials were included. The severity of the pulpal
      reaction was ranked on hematoxylin/eosin stained sections according to FDI
      standards. The further parameters recorded were: (1) the presence or absence of
      bacteria on the cavity walls was noted on Brown and Brenn stained sections; (2)
      the remaining dentin thickness was measured and the teeth classified into three
      groups (< 500, 500-1000, > 1000 microns); and (3) the post-operative delay before
      extraction was recorded and classified as short time (< 5 weeks) or long time (>
      5 weeks). Three two-way analyses of variance (ANOVA) followed by Kruskall and
      Wallis tests evaluated the influence of the three parameters on pulpal reaction
      severity. The third ANOVA also compared pulpal reactions under the different
      materials when the teeth were pooled, on bacteria free teeth and on bacteria
      contaminated teeth. RESULTS: The first ANOVA ranked by decreasing order of
      importance: the presence of bacteria (p < 0.0001), the remaining dentin thickness
      (p = 0.02) and the post-operative delay (p = 0.04). The second ANOVA showed no
      difference among the restorative materials when bacteria were present on the
      cavity walls. SIGNIFICANCE: The presence of bacteria on the cavity walls is the
      main factor influencing pulpal reaction under restorative materials, but does not
      account for 100% of the cases.

PMID- 10967194
TI  - Dimensional changes of demineralized dentin treated with HEMA primers.
AB  - OBJECTIVES: The purpose of this study was to measure the dimensional changes of
      demineralized dentin before and after application of HEMA (2-hydroxyethyl
      methacrylate) by confocal laser scanning microscopy (CLSM). METHODS: The middle
      portion of bovine dentin was ground, polished, and covered with a vinyl tape with
      a 4-mm hole punched through it. A strip of polysiloxane impression material was
      then placed across the center of the dentin surface to preserve a strip of the
      original unetched surface. Dentin surfaces were etched with 32% phosphoric acid
      for 60 s and rinsed with water. The impression material was then removed and the
      following sequential steps were performed: the dentin surface was mildly air
      dried, then strongly air-dried, then treated with either 35 wt.% HEMA/water or
      100 wt.% HEMA and mildly air-dried, and then strongly dried again. The shrinkage
      of the demineralized dentin surface from the original unetched level was measured
      by CLSM in each step and results analyzed by one-way ANOVA. RESULTS: The
      dimensional changes of demineralized dentin after mild air drying were
      approximately -1 micron and, following strong air drying, resulted in -5 microns
      shrinkage. Following the application of 35 wt.% HEMA/water, the height of the
      demineralized dentin changed to a level of -3.3 microns, but then shrank to -4.8
      microns after strong drying. ANOVA indicated that re-expansion of the shrunken
      etched dentin was significant (p < 0.05); however, the treated surface collapsed
      when it was strongly dried again (p < 0.05). 100% HEMA did not re-expand the
      shrunken demineralized dentin under any of the application on protocols (p >
      0.05). SIGNIFICANCE: Thirty-five wt.% HEMA in water re-expanded the collapsed
      demineralized dentin matrix, however not to the original level. One hundred wt.%
      HEMA did not cause any re-expansion.

PMID- 10967195
TI  - Optimal specimen geometry in bonded-disk shrinkage-strain measurements on light
      cured biomaterials.
AB  - OBJECTIVES: The aim was to determine the effect on apparent shrinkage-strain
      values of varying specimen aspect ratio in the bonded-disk configuration. Thereby
      one source of possible inter-laboratory variation might be understood and
      eliminated. METHODS: The bonded-disk procedure was followed and applied to three
      representative resin-composites. However, specimen sub-groups were examined, each
      of different diameters (3.5, 5.0, 7.0 and 9.0 mm), corresponding to C-factors in
      the range 0.45-7.0. RESULTS: For each material, no statistically significant
      difference was apparent between data obtained with 7 and 9 mm diameter specimens.
      However, statistically significant reductions (p < 0.05, Scheffe and SNK) were
      apparent at 5.0 and 3.5 mm diameter, in the range 14-18% of the maximum 'true'
      value. For each material, the diameter (d)-dependence of apparent shrinkage
      strain (epsilon) was given by the curve fit expression: epsilon = A - B/d2.
      SIGNIFICANCE: For accurate determination of maximum final equilibrium shrinkage
      strain values, a high aspect ratio (7-9:1) of the bonded-disk should be utilised.
      This is important for accurate comparison of data from proposed low-shrinkage
      amalgam-replacement materials.

PMID- 10967196
TI  - Antibacterial effect of silver-zeolite on oral bacteria under anaerobic
      conditions.
AB  - OBJECTIVES: The purpose of this study was to evaluate the antibacterial effect of
      silver-zeolite (SZ) against oral bacteria under anaerobic conditions. METHODS:
      The antibacterial activity of SZ was evaluated by determining the minimum
      inhibitory concentrations (MICs) using two-fold serial dilutions of SZ in Brain
      Heart Infusion broth. Release of Ag+ into the broth was measured by an atomic
      absorption technique. RESULTS: SZ inhibited the growth of the bacteria tested
      under anaerobic conditions. The MIC of SZ ranged between 256 and 2048
      micrograms/ml, which corresponded to a range of 4.8-38.4 micrograms/ml of Ag+.
      All strains grew in broth containing 16,384 micrograms/ml of type-A zeolite.
      SIGNIFICANCE: These results suggested that SZ may be a useful vehicle to provide
      antibacterial activity to dental materials used even under anaerobic conditions
      such as deep in the periodontal pocket.

PMID- 10967197
TI  - The cardiac renin-angiotensin system: novel signaling mechanisms related to
      cardiac growth and function.
AB  - Angiotensin II, the effector peptide of the renin-angiotensin system, has been
      demonstrated to be involved in the regulation of cellular growth of several
      tissues in response to developmental, physiological, and pathological processes.
      The recent identification of renin-angiotensin system components and localization
      of angiotensin II receptors in cardiac tissue suggests that locally synthesized
      Ang II can modulate functional and growth responses in cardiac tissue. In this
      review, regulation of the cardiac RAS is discussed, with an emphasis on growth
      related Ang II signal transduction systems.

PMID- 10967198
TI  - Signal transduction of angiotensin II type 1 receptor through receptor tyrosine
      kinase.
AB  - In cultured vascular smooth muscle cells, the angiotensin II (AngII) type-1
      (AT(1)) receptor generates growth-promoting signals via the epidermal growth
      factor (EGF) receptor system. This 'transactivation' mechanism now appears to be
      utilized by a variety of G-protein-coupled receptors in many cells. The AngII
      induced EGF receptor transactivation leads to activation of downstream signaling
      molecules including Ras, ERK, c-fos, Akt/protein kinase B, and p70 S6 kinase. We
      propose three possible mechanisms may be involved in the transactivation, (i) an
      upstream tyrosine kinase, (ii) reactive oxygen species, and (iii) a juxtacrine
      activation of the EGF receptor ligand. Whether the EGF receptor signal
      transduction induced by AngII plays an essential role in cardiovascular
      remodeling remains to be investigated.

PMID- 10967199
TI  - Reactive oxygen species as mediators of angiotensin II signaling.
AB  - Angiotensin II stimulates a plethora of signaling pathways leading to cell growth
      and contraction. Recent work has shown that reactive oxygen species are involved
      in transducing many of the effects of angiotensin II, and are in fact produced in
      response to agonist-receptor binding. Angiotensin II stimulates a NAD(P)H oxidase
      to produce superoxide and hydrogen peroxide, both of which may act on
      intracellular growth-related proteins and enzymes to mediate the final
      physiological response. Of particular importance is hydrogen peroxide, which
      mediates angiotensin II stimulation of such important intracellular signals as
      EGF-receptor transactivation, p38 mitogen activated protein kinase, and Akt.
      Future work will be directed towards identifying other important redox-sensitive
      signaling pathways and their relationship to the physiology and pathophysiology
      of the renin-angiotensin system.

PMID- 10967200
TI  - Mechanisms and functions of AT(1) angiotensin receptor internalization.
AB  - The type 1 (AT(1)) angiotensin receptor, which mediates the known physiological
      and pharmacological actions of angiotensin II, activates numerous intracellular
      signaling pathways and undergoes rapid internalization upon agonist binding.
      Morphological and biochemical studies have shown that agonist-induced endocytosis
      of the AT(1) receptor occurs via clathrin-coated pits, and is dependent on two
      regions in the cytoplasmic tail of the receptor. However, it is independent of G
      protein activation and signaling, and does not require the conserved NPXXY motif
      in the seventh transmembrane helix. The dependence of internalization of the
      AT(1) receptor on a cytoplasmic serine-threonine-rich region that is
      phosphorylated during agonist stimulation suggests that endocytosis is regulated
      by phosphorylation of the AT(1) receptor tail. beta-Arrestins have been
      implicated in the desensitization and endocytosis of several G protein-coupled
      receptors, but the exact nature of the adaptor protein required for association
      of the AT(1) receptor with clathrin-coated pits, and the role of dynamin in the
      internalization process, are still controversial. There is increasing evidence
      for a role of internalization in sustained signal generation from the AT(1)
      receptor. Several aspects of the mechanisms and specific function of AT(1)
      receptor internalization, including its precise mode and route of endocytosis,
      and the potential roles of cytoplasmic and nuclear receptors, remain to be
      elucidated.

PMID- 10967201
TI  - Angiotensin-(1-7): an update.
AB  - The renin-angiotensin system is a major physiological regulator of arterial
      pressure and hydro-electrolyte balance. Evidence has now been accumulated that in
      addition to angiotensin (Ang) II other Ang peptides [Ang III, Ang IV and Ang-(1
      7)], formed in the limited proteolysis processing of angiotensinogen, are
      importantly involved in mediating several actions of the RAS. In this article we
      will review our knowledge of the biological actions of Ang-(1-7) with focus on
      the puzzling aspects of the mediation of its effects and the interaction Ang-(1
      7)-kinins. In addition, we will attempt to summarize the evidence that Ang-(1-7)
      takes an important part of the mechanisms aimed to counteract the vasoconstrictor
      and proliferative effects of Ang II.

PMID- 10967202
TI  - Calcitonin gene-related peptide (CGRP) inhibits contractions of the prostatic
      stroma of the rat but not the guinea-pig.
AB  - This study investigated the presence and effects of calcitonin gene-related
      peptide (CGRP) within the rat and guinea-pig prostate glands. Immunohistochemical
      studies demonstrated that CGRP immunoreactive nerve fibres are sparsely
      distributed throughout the prostatic fibromuscular stroma in both species. These
      CGRP immunopositive nerve fibres shared a similar distribution profile but were
      not colocalized with tyrosine hydroxylase immunopositive nerve fibres which also
      innervate the prostatic stroma of these species. Nerve terminals within rat and
      guinea-pig prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10
      Hz, 20 pulses every 60 s). In guinea-pig preparations, application of human alpha
      CGRP, rat adrenomedullin or rat amylin (0.1 nM-1 microM) had no effect on
      responses to field stimulation. In contrast, both rat and human alpha-CGRP (10 pM
      300 nM), rat adrenomedullin (0.3 nM-1 microM) and rat amylin (3 nM-1 microM)
      concentration-dependently inhibited electrically evoked contractile responses in
      the rat prostate. The relative order of potency was rat alpha-CGRP=human alpha
      CGRP>rat adrenomedullin>rat amylin. The inhibition by rat alpha-CGRP of field
      stimulation-induced contractions in the rat prostate was competitively
      antagonized by human CGRP((8-37)) (1, 3 and 10 microM) with a pA(2) of 6.20+/
      0.13. Rat alpha-CGRP (10 nM) attenuated contractile responses of the rat prostate
      to exogenously added noradrenaline (1-100 microM). Inhibitory concentration
      response curves to rat alpha-CGRP in rat prostates were unaffected by
      preincubation in either glibenclamide (10-100 microM), N-nitro-L-arginine methyl
      ester (L-NAME) (10 microM), bestatin (10 microM), captopril (10 microM) or
      phosphoramidon (3 microM). Our results indicate that CGRP-induced inhibition of
      electrically evoked contractions in the rat prostate occurs through activation of
      postjunctional CGRP(2) receptors which act independently of a K(ATP) channel or
      nitrergic mechanisms. Degradation of rat alpha-CGRP via peptidases does not
      appear to occur in the rat prostate.

PMID- 10967203
TI  - Effects of centrally or systemically injected glucagon-like peptide-1 (7-36)
      amide on release of neurohypophysial hormones and blood pressure in the rat.
AB  - The present study was designed to compare the effects of glucagon-like peptide-1
      (7-36) amide (GLP-1) injected centrally or systemically in a dose range of 10
      10000 ng on the vasopressin and oxytocin release as well as the blood pressure in
      the rat. The urethane-anaesthetised Wistar male and female rats were fitted with
      venous as well as arterial catheters and, in the second study, additionally with
      the intracerebroventricular cannula. The arterial blood pressure was monitored
      throughout the experiment. The plasma vasopressin/oxytocin concentrations were
      measured in blood samples taken 15 min before and 5, 15 and 30 min after the
      intravenous or intracerebroventricular GLP-1 injection. No gender-dependent
      differences were seen as to the GLP-1 effect on the blood pressure or the hormone
      release. GLP-1 administered centrally or systemically at low doses (10 or 100 ng)
      either showed a hypertensive or biphasic (an increase followed by a decrease in
      the blood pressure) effect. On the other hand, 1000 or 10000 ng GLP-1 caused a
      clear increase of the blood pressure regarding the way of injection. When
      injected systemically, GLP-1 increased the release of both neurohypophysial
      hormones. When injected centrally, however, GLP-1 either enhanced or, at low
      doses, significantly reduced the plasma vasopressin/oxytocin levels. The effect
      on the blood pressure seems to be independent of the possible pressor effect of
      endogenous vasopressin. It is concluded that GLP-1 may modulate the function of
      the hypothalamo-neurohypophysial system as well as the cardiovascular system
      through both the central and systemic mechanisms.

PMID- 10967204
TI  - Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) relax
      cholecystokinin-induced tension in guinea pig gallbladder strips.
AB  - Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) have
      been shown to relax various types of smooth muscle, e.g. vascular, uterine and
      gastric. This study demonstrates that PTH and PTHrP both relaxed cholecystokinin
      octapeptide (CCK)-induced tension in guinea pig gallbladder strips. This
      relaxation was concentration-dependent. The use of PTHrP (7-34) blocked the
      relaxant effect of both agents. This suggested PTH and PTHrP were acting through
      the same receptor. The use of Rp-cAMPs, an inhibitor of cAMP activation of
      protein kinase A, and H-89, a selective inhibitor of protein kinase A, suggested
      that cAMP mediated the relaxant action of PTH and PTHrP. The use of iberiotoxin
      indicated that the high conductance Ca(2+)-activated potassium channels also
      mediated the actions of PTH/PTHrP. The use of KT5823, a selective blocker of
      protein kinase G, also decreased the amount of relaxation induced by PTH/PTHrP.
      This suggested that crosstalk between the two second messenger (cAMP and cGMP)
      systems occurred.

PMID- 10967205
TI  - Effect of middle cerebral artery occlusion on the passage of pituitary adenylate
      cyclase activating polypeptide across the blood-brain barrier in the rat.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be a
      potent neuroprotective agent in global and focal ischemia. We demonstrated that
      PACAP could cross the blood-brain barrier (BBB) by a saturable transport system,
      and a systemic administration of PACAP reduced the infarct induced by unilateral
      middle cerebral artery occlusion (MCAO). Therefore, we studied whether this
      transport system is affected by MCAO in the rat. The entry of PACAP38 into the
      brain was compared in five groups: control, 4, 6, 24, and 48 h after MCAO.
      [(125)I]PACAP38 was injected intravenously and serum and various brain regions
      were collected 3 min later. The rate of entry into the brain of PACAP38 was also
      determined. We showed that PACAP entered the rat brain via a rapid transport
      system when the BBB is intact. After transient (2 h) unilateral MCAO, all regions
      of the brain, showed a selective increase in the passage of PACAP38 across the
      BBB after 4 h after the occlusion, which was not related to any generalized
      change in the permeability of the BBB, as measured with albumin. A significant
      decrease in the amount of PACAP38 entering the brain was observed in the 6- and
      24-h groups, but it returned to the baseline level in the 48-h group. These
      results suggest that focal cerebral ischemia can selectively modify the passage
      of PACAP38 across the BBB, in both damaged and undamaged sides of the brain, and
      that these changes in influx are not solely due to the disruption of BBB. These
      findings imply the necessity of adjusting the dose of intravenously administered
      PACAP38 in order to maximize its therapeutic effect on the brain damage resulting
      from focal ischemia

PMID- 10967208
TI  - Bacteria in the cold deep-sea benthic boundary layer and sediment-water interface
      of the NE Atlantic.
AB  - This is a short review of the current understanding of the role of microorganisms
      in the biogeochemistry in the deep-sea benthic boundary layer (BBL) and sediment
      water interface (SWI) of the NE Atlantic, the gaps in our knowledge and some
      suggestions of future directions. The BBL is the layer of water, often tens of
      meters thick, adjacent to the sea bed and with homogenous properties of
      temperature and salinity, which sometimes contains resuspended detrital
      particles. The SWI is the bioreactive interface between the water column and the
      upper 1 cm of sediment and can include a large layer of detrital material
      composed of aggregates that have sedimented from the upper mixed layer of the
      ocean. This material is biologically transformed, over a wide range of time
      scales, eventually forming the sedimentary record. To understand the microbial
      ecology of deep-sea bacteria, we need to appreciate the food supply in the upper
      ocean, its packaging, passage and transformation during the delivery to the sea
      bed, the seasonality of variability of the supply and the environmental
      conditions under which the deep-sea bacteria grow. We also need to put into a
      microbial context recent geochemical findings of vast reservoirs of intrinsically
      labile organic material sorped onto sediments. These may well become desorped,
      and once again available to microorganisms, during resuspension events caused by
      deep ocean currents. As biotechnologists apply their tools in the deep oceans in
      search of unique bacteria, an increasing knowledge and understanding of the
      natural processes undertaken and environmental conditions experienced by deep-sea
      bacteria will facilitate this exploitation.

PMID- 10967206
TI  - Dihydrocapsaicin treatment depletes peptidergic nerve fibers of substance P and
      alters mast cell density in the respiratory tract of neonatal sheep.
AB  - In the present study we administered dihydrocapsaicin (DHC) to neonatal lambs to
      deplete C-fibers of neuropeptides. We measured the density of substance P (SP)
      fibers in nasal septum to assess the effectiveness of the treatment at 3, 9, and
      21 days. The numbers of mast cells in the upper and lower respiratory tract were
      determined at the same time points and histamine content was determined from lung
      tissue. DHC treatment depleted SP-fibers for up to the 21 day time point. This
      depletion was estimated as 85% in comparison with controls. In vehicle-treated
      lambs, the density of SP-fibers decreased progressively with age, but not to the
      degree of DHC-treated lambs whose SP-fibers were depleted from the initial 3-day
      measurement. In both, vehicle- and DHC-treated lambs, numbers of mast cells
      increased progressively with time; however, the density of mast cells was
      augmented in the entire respiratory tract of DHC-treated animals. Apparently, DHC
      treatment exerts a single and initial effect in increasing mast cells whereas
      time maintains a continuous influence; both factors exert their influence
      independently. Despite large numbers of mast cells in DHC-treated animals,
      histamine content in the lung had similar levels as controls. Our study provides
      fundamental data for a better understanding of conditions that may influence
      defense mechanisms dependent on the mast cell-nerve axis in the respiratory
      tract.

PMID- 10967209
TI  - Adhesion and development of the root rot fungus (Heterobasidion annosum) on
      conifer tissues: effects of spore and host surface constituents.
AB  - The objective of this study was to correlate the occurrence of particular root
      and woody stump surface components with the ability of spores of the root rot
      fungus (Heterobasidion annosum) to adhere, germinate and establish on conifer
      tissues. With the aid of high performance liquid chromatography, several sugars
      (pinitol, xylitol, dulcitol, mannitol, D-glucose, mannose, fructose) were
      detected on both stump and fine root surfaces of Scots pine and Norway spruce. Of
      all the sugars observed, xylose and arabinose were poorly utilized for initiation
      of germ tube growth whereas spore germination was enhanced in the presence of D
      glucose, mannose or fructose. Oxidation of these sugars by pretreatment of wood
      discs or roots with periodic acid abolished the ability of the spores to
      germinate. Non-sugar components such as long chain fatty acids on spores and root
      surfaces as detected with nuclear magnetic resonance were found to have a
      significant influence on adhesion and initiation of germ tube development.
      Removal of these aliphatic compounds from the root surface increased spore
      germination by 2-fold, whereas similar treatment on spores led to a 5-fold
      decrease in adhesiveness to root material. In vitro studies revealed that the di
      ethyl ether extract from the roots had no long term adverse effect on spore
      germination which suggests that the fungus may possess the capability to detoxify
      this substance. Similarly, adhesion of spores was affected by low and freezing
      temperatures. The role of significant levels of mannitol and trehalose
      accumulated in spores and hyphae of the fungi on viability, survival and
      tolerance to adverse conditions such as oxidative stress, freezing and
      desiccation are discussed.

PMID- 10967210
TI  - Diverse, yet-to-be-cultured members of the Rubrobacter subdivision of the
      Actinobacteria are widespread in Australian arid soils.
AB  - Phylogenetic analyses of ribosomal RNA gene sequences (rDNAs) retrieved from an
      Australian desert soil sample (Sturt National Park) revealed the presence of a
      number of clones which branched deeply from the high GC Gram-positive division
      line of descent. The most abundant group of these clones were related to
      Rubrobacter. An oligonucleotide probe was designed to have broad specificity to
      Rubrobacter and relatives. This probe was used to interrogate eight rDNA
      libraries representing four distinct land forms within the Australian arid zone.
      Relative abundance of Rubrobacter-relatives in these samples ranged from 2.6 to
      10.2%. Clones from these libraries were selected for sequence analysis on the
      basis of a heteroduplex mobility assay to maximise the diversity represented in
      the sample. Phylogenetic analyses of these rDNA clones and Rubrobacter-related
      clones reported in the literature show strong support for three distinct groups.
      Database-searching revealed 'Rubrobacteria' were relatively abundant in a number
      of published soil rDNA libraries but absent from others. A PCR assay for group-1
      'Rubrobacteria' was used to test for their presence in 21 environmental samples.
      Only marine and arid-zone soil samples gave positive PCR results. Taken together
      these results indicate 'Rubrobacteria' are a widespread group of variable
      abundance and diversity.

PMID- 10967211
TI  - The impact of surface attachment on cadmium accumulation by Pseudomonas
      fluorescens H2.
AB  - Cadmium accumulation by Pseudomonas fluorescens H2 attached to glass surfaces and
      by cells free in suspension in maleate buffer was compared and showed several
      major differences. The time to saturation of cells with Cd(2+) was different for
      attached and free cells, although both showed biphasic uptake of Cd(2+). The
      accumulation of Cd(2+) by free cells was inhibited by the presence of zinc but
      remained several orders of magnitude higher than accumulation by attached cells.
      The presence of Zn(2+), however, did not inhibit Cd(2+) uptake by cells attached
      to the solid substratum. Cadmium uptake still increased with Cd(2+) concentration
      for both free and attached cells in the presence of Zn(2+). The accumulation of
      Cd(2+) by both free and attached cells increased with pH up to pH 11. The
      presence of a metabolic inhibitor, carbomyl cyanide m-chlorophenyl-hydrazone,
      reduced the uptake of Cd(2+) by free cells by 40% but reduced uptake by attached
      cells by only 25%. Approximately 65% of Cd(2+) accumulated by cells free in
      suspension was associated with the cell wall, 33% was present in the cytoplasm
      and only 2% was bound to exopolymer. The results suggest that the characteristics
      of heavy metal accumulation by bacterial cells are substantially affected by
      attachment to solid surfaces.

PMID- 10967212
TI  - Comparison of methods to investigate microbial populations in soils under
      different agricultural management.
AB  - The microbial community in sludge-treated and nearby untreated soils was
      investigated using direct microscopic counting, plate culture, carbon substrate
      utilisation (Biolog), and fatty acid methyl esters. Long-term sewage sludge
      applications had resulted in higher concentrations of organic carbon and had
      altered other factors in the soil, including the concentration of metals.
      Bioluminescence was inhibited in assays of the sludge-treated soil, although
      microbial counts were similar in all soils. A detailed analysis of carbon
      substrate utilisation patterns and fatty acid methyl esters showed qualitative
      differences in the microbial populations. This work shows that a variety of
      approaches are required to assess microbial communities in soil where, despite
      large differences in land management, the populations are similar in size and
      overall composition.

PMID- 10967213
TI  - Viscosinamide-producing Pseudomonas fluorescens DR54 exerts a biocontrol effect
      on Pythium ultimum in sugar beet rhizosphere.
AB  - Growth inhibition of the root pathogen Pythium ultimum by the biocontrol agent
      Pseudomonas fluorescens DR54 inoculated on sugar beet seeds was studied in a soil
      microcosm. Plant emergence was followed, together with bacterial rhizosphere
      colonization, antibiotic production and effects on fungal growth. P. fluorescens
      DR54 inoculation of the P. ultimum-challenged seeds improved plant emergence
      after 7 days compared to a control without the biocontrol strain. At this time,
      P. fluorescens DR54 was the dominating colony-forming pseudomonad in rhizosphere
      soil samples from inoculated seedlings as shown by immuno-staining with a strain
      specific antibody. Viscosinamide, a cyclic lipopeptide, which has previously been
      identified as a major antagonistic determinant produced by P. fluorescens DR54
      and shown to induce physiological changes in P. ultimum in vitro, could be
      detected in the rhizosphere samples. The impact of P. fluorescens DR54 on the
      growth and activity of P. ultimum was studied by direct microscopy after staining
      with the vital fluorescent dyes Calcofluor white and fluorescein diacetate. P.
      fluorescens DR54 caused reduction in P. ultimum mycelial density, oospore
      formation and intracellular activity. Further, Pythium oospore formation was
      absent in the presence of P. fluorescens DR54. A striking effect on zoospore
      forming indigenous fungi was also observed in microcosms with P. fluorescens DR54
      and, thus, where viscosinamide could be detected; a large number of encysted
      zoospores were seen in such microcosms both with and without P. ultimum
      infections. In vitro studies confirmed that purified viscosinamide induced
      encystment of Pythium zoospores.

PMID- 10967214
TI  - Molecular analysis of microbial communities in mobile deltaic muds of
      Southeastern Papua New Guinea.
AB  - A culture-independent examination of microbial diversity in mobile deltaic
      sediments from the Gulf of Papua, Papua New Guinea, was conducted by sequence
      analysis of 16S rDNA clone library. Universal small subunit primers were used to
      amplify DNA extracted from the sediment. Of 91 clones randomly selected from the
      library, 33 contained unique non-chimeric sequences. Analysis of these unique
      sequences showed that the majority of them belonged to bacteria (94.5%), with
      proteobacteria being the dominant division (74.8%). One sequence belonging to
      Crenarchaeota and another to Euryarchaeota were found as well. Bacterial
      sequences belonging to the following major divisions were identified: Cytophaga
      Flexibacter-Bacteroides (5.5%), low GC Gram-positives (1.1%), Nitrospira group
      (3.3%), OP8 candidate division (2.2%), OS-K candidate division (2.2%),
      Planctomyces (1.1%), alpha, delta, gamma and epsilon-subdivisions of
      Proteobacteria (4.4, 20.9, 19.8 and 23.1%, respectively) and Spirochaetales
      (4.4%). The composition of 16S rDNA library of the Gulf of Papua sediments is
      similar to those for deepwater sediments from around the Japanese Islands,
      indicating a possible cosmopolitan nature of microbial communities in suboxic and
      anoxic sediments of the Pacific. It appears that many Papua/New Guinea sequences
      are loosely affiliated with bacteria involved in sulfur cycling, thus supporting
      the hypothesis that the sulfur cycle may be important in early diagenesis of
      suboxic sediments.

PMID- 10967215
TI  - Characterization of the microbial community of lotic organic aggregates ('river
      snow') in the Elbe River of Germany by cultivation and molecular methods.
AB  - Aerobic and anaerobic cultivation techniques, 16S rDNA-based phylogeny, and
      fluorescent in situ hybridization were used to describe the phylogenetic
      diversity and physiological versatility of lotic microbial aggregates ('river
      snow') obtained from the river Elbe. In the course of the year the 'river snow'
      community changed. It was characterized by a great bacterial diversity in spring,
      the predominant occurrence of algae in summer and reduction of the total
      bacterial cell count in autumn and winter. In all 'river snow' samples, more than
      70% of the bacteria counted with the general DNA stain DAPI also hybridized with
      the Bacteria-specific probe EUB338. In situ analysis of the bacterial 'river
      snow' community with a comprehensive suite of specific rRNA-targeted probes
      revealed population dynamics to be governed by seasonal factors. During all
      seasons, beta-Proteobacteria constituted the numerically most important bacterial
      group forming up to 54% of the total cell counts. In contrast to this, the
      relative abundance of other major bacterial lineages ranged from 2% for the order
      Planctomycetales to 36% for Cytophaga-Flavobacteria. Cultivation of 'river snow'
      under aerobic and anaerobic conditions with a variety of different media resulted
      in the isolation of 40 new bacterial strains. Phenotypic and phylogenetic
      analyses revealed these new strains to be mostly unknown organisms affiliated to
      different bacterial phyla. Application of newly developed specific
      oligonucleotide probes proved the cultivated bacteria, including clostridia and
      the numerically abundant beta-Proteobacteria, as relevant in situ members of the
      'river snow' community.

PMID- 10967216
TI  - Preface

PMID- 10967217
TI  - Current status of DNA vaccines in veterinary medicine.
AB  - DNA vaccination entails administration of the DNA itself encoding antigen to
      direct synthesis of the antigen directly in the target organism. The target
      organism's immune system recognizes the antigen, and generates humoral (antibody)
      and/or cell-mediated immune response. DNA vaccines afford numerous advantages
      over conventional vaccines, including ease of production, stability and
      transport. They overcome the need to cultivate dangerous infectious agents, and
      provide a possibility to vaccinate against multiple pathogens in a single shot.
      DNA vaccination is beginning to be explored for many pathogens of veterinary
      interest. The status of DNA vaccines in poultry, livestock and companion animals
      is reviewed here. While examples of DNA vaccines being tested in the veterinary
      field are not numerous, the early studies highlight the potential DNA vaccinology
      offers in veterinary medicine.

PMID- 10967218
TI  - Recent advances in the use of DNA vaccines for the treatment of diseases of
      farmed animals.
AB  - DNA-based vaccination constitutes one of the most recent approaches to vaccine
      development. This technology is in principle one of the most simple and yet
      versatile methods of inducing both humoral and cellular immune responses, as well
      as protection against a variety of infectious agents. However, although immune
      responses have been induced in a number of larger species, most information on
      the efficacy of DNA immunization has been generated in mice. In this review the
      information available to date about the use of DNA vaccines in farmed animals,
      including cattle, pigs and poultry, is presented. The areas that need specific
      attention in the future to bring this technology to the market are discussed,
      including the issues concerning delivery, safety, compatibility of plasmids in
      multivalent vaccines and the potential of using immune stimulants as part of a
      DNA vaccine.

PMID- 10967219
TI  - Application of DNA vaccine technology to aquaculture.
AB  - The aquaculture industry needs to augment its global production and efficiency to
      meet the increasing consumer needs for fish and shellfish products.
      Unfortunately, infectious diseases have been a major impediment to the
      development and profitability of fish farms. While vaccines offer the most
      efficient way to control infectious pathogens, current products have only been
      successful against some diseases. These are mostly bacterial, and there are still
      several important diseases, mainly of viral and parasitic origin, for which no
      prophylactic treatment exists. DNA vaccines, compared to traditional antigen
      vaccines, have several practical and immunological advantages that make them very
      attractive for the aquaculture industry. The early success of DNA vaccines in
      animal models was very encouraging, but fish are unique in many aspects, and
      findings with other classes of vertebrate, namely mammals and birds, do not
      necessarily apply to aquatic animals. However, more recent studies with reporter
      genes showed that fish cells efficiently express foreign proteins encoded by
      eukaryotic expression vectors. A piscine-specific backbone vector might
      eventually improve immune responses to DNA vaccines, but there is already strong
      direct evidence for the induction of protective immunity with currently available
      plasmids. Immune responses to plasmid DNA injected intramuscularly (IM) into fish
      are characterized by the production of antibodies, which have been shown to be
      neutralizing in two different viral disease models. There is also indirect
      evidence suggesting the induction of cell-mediated immunity. Despite this
      evidence, immune responses to DNA vaccines have only been poorly characterized in
      fish because of the limited knowledge of the piscine immune system, and the small
      number of studies on the subject. Apart from optimizing the efficiency of DNA
      vaccines, other important issues, such as safety and production cost will be
      determinants for the potential application of this technology in commercial fish
      farms. Alternative methods of administration will also have to be developed for
      small fish and low-valued species, for which IM injection is not practical and/or
      cost effective.

PMID- 10967220
TI  - Transcutaneous immunization of domestic animals: opportunities and challenges.
AB  - Transcutaneous immunization (TCI), the topical application of antigen and
      adjuvant directly onto intact skin, can safely and effectively elicit systemic
      immune responses in mice and humans against a variety of antigens. This novel
      method of vaccine delivery has the potential to provide a safe and convenient
      method by which vaccines may be delivered to elicit protective immunity in
      domestic animals. To date, however, immune responses induced by TCI in companion
      and production animals has not been reported. In this report, we demonstrate that
      TCI may be widely applicable to many animals. Immune responses elicited by TCI
      require further optimization for each antigen and species, and success may depend
      upon the structure and composition of the skin of the target species. The
      prospect of TCI as a practical and broadly applicable approach to vaccination in
      veterinary medicine is discussed in the context of these challenges.

PMID- 10967221
TI  - Applications of genetic engineering in veterinary medicine.
AB  - A mutation of just one gene will cause abnormal cell behavior leading to the
      synthesis of a dysfunctional protein. This mutation will inevitably result in the
      cell functioning only marginally or not at all. Other genetic mutations interfere
      with the cell's normal life cycle, especially the cell-division cycle. The goal
      behind recombinant DNA technology is to deliver the correct version of a mutated
      gene to the cell so that the expression will lead to the normal production of
      protein and the restoration of normal cell function. This can be considered
      qualitatively different from other conventional treatments due to genetic
      material being a putative therapeutic agent. By altering the genetic material of
      cells, gene therapy may correct, or one day cure, the specific disease
      pathophysiology. Genetic engineering has been used in veterinary medicine to
      diagnose, prevent and treat diseases, breed different species and produce
      transgenic animals for therapeutic proteins or xenografting. In this review the
      current status of recombinant DNA technology and its application in veterinary
      medicine together with the obstacles to, and applications of, genetic engineering
      in veterinary medicine are discussed.

PMID- 10967222
TI  - Potential applications and delivery strategies for bone morphogenetic proteins.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional cytokines which are
      members of the Transforming Growth Factor-beta superfamily. They are the only
      signaling molecules which can singly induce de novo bone formation at orthotopic
      and heterotopic sites and their osteoinductive potency makes them clinically
      valuable as alternatives to bone graft. Several means of delivering BMPs to
      patients are undergoing evaluation including systemic administration, gene
      transfer and local matrix delivery vehicle implantation. The latter methodology
      is in advanced stages of development for application in humans in the treatment
      of selected spinal fusions, fracture repairs, craniomaxillofacial surgery and
      periodontal injury and disease. The BMPs are also widely distributed in non
      skeletal tissues such as nerve, gastrointestinal tract, kidney, heart and lungs
      and they have a central role in vertebrate and non-vertebrate organogenesis.
      Initial studies indicate that the BMPs have neuro, cardio and reno-protective
      actions and it is likely that therapeutic indications for their use will extend
      well beyond skeletal disease and injury.

PMID- 10967223
TI  - Ligand-mediated tissue specific drug delivery.

PMID- 10967224
TI  - Endogenous carriers and ligands in non-immunogenic site-specific drug delivery.
AB  - Targeted drug delivery has gained recognition in modern therapeutics and attempts
      are being made to explore the potentials and possibilities of cell biology
      related bioevents in the development of specific, programmed and target oriented
      systems. The components which have been recognized to be tools include receptors
      and ligands, where the receptors act as molecular targets or portals, and
      ligands, with receptor specificity and selectivity, are trafficked en route to
      the target site. Although ligands of exogenous or synthetic origin contribute to
      the selectivity component of carrier constructs, they may impose immunological
      manifestations of different magnitudes. The latter may entail a continual quest
      for bio-compatible, non-immunogenic and target orientated delivery. Endogenous
      serum, cellular and extracellular bio-ligands interact with the colloidal carrier
      constructs and influence their bio-fate. However, these endogenous bio-ligands
      can themselves serve as targeting modules either in their native form or
      engineered as carrier cargo. Bio-regulatory, nutrient and immune ligands are
      sensitive, specific and effective site directing handles which add to targeted
      drug delivery. The present review provides an exhaustive account of the
      identified bio-ligands, which are not only non-immunogenic in nature but also
      site-specific. The cell-related bioevents which are instrumental in negotiating
      the uptake of bio-ligands are discussed. Further, a brief account of ligand
      receptor interactions and the set of biological events which ensures ligand
      driven trafficking of the ligand-receptor complex to the cellular interior is
      also presented. Since ligand-receptor interaction is a critical pre-requisite for
      negotiating cellular uptake of endogenous ligands and anchored carrier cargo, an
      attempt has been made to identify differential expression of receptors and bio
      ligands under normal and etiological conditions. Studies which judiciously
      utilized bio-ligands or their analogs in negotiating site-specific drug delivery
      have been reviewed and presented. Targeted delivery of bioactives using
      endogenous bio-ligands offers enormous options and opportunities through carrier
      construct engineering and could become a future reality in clinical practice.

PMID- 10967225
TI  - The use of phage display for the development of tumour targeting agents.
AB  - One way to improve the selectivity of therapeutic molecules in clinical oncology
      would be to target them on the tumour site, thereby sparing normal tissues. The
      development of targeted therapeutic methodologies relies in most cases on the
      availability of binding molecules specific for tumour-associated markers. The
      display of repertoires of polypeptides on the surface of filamentous phage,
      together with the efficient selection-amplification of the desired binding
      specificities using affinity capture, represents an efficient route towards the
      isolation of specific peptides and proteins that could act as vehicles for tumour
      targeting applications. Most investigations in this area of research have so far
      been performed with phage derived recombinant antibodies, which have been shown
      to selectively target tumour-associated markers both in preclinical animal models
      and in the clinic. However, future developments with other classes of
      polypeptides (small constrained peptides, small globular proteins) promise to be
      important for the selective delivery of therapeutic agents to the tumour site.

PMID- 10967226
TI  - Virosomes: evolution of the liposome as a targeted drug delivery system.
AB  - The drug delivery system (DDS) is attractive as a therapeutic method. Liposomes
      are of particular interest as a DDS because they can reduce drug toxicity, and
      offer promise as gene carriers. An evolution has occurred in the construction of
      liposomes in the effort to develop efficient vectors for in vivo use. To avoid
      uptake by the reticuloendothelial system (RES); Lipid components have been
      optimized. To enhance tissue targeting, liposome surface has been modified with
      antibodies or ligands recognized by specific cell types. To enhance the
      efficiency of gene delivery by the introduction of molecules directly into cells,
      virosomes have been developed by combining liposomes with fusiogenic viral
      envelope proteins. Liposomes are now being used in the treatment of intractable
      human diseases such as cancer and monogenic disorders. In the future, many
      medical procedures will be performed using liposomes.

PMID- 10967227
TI  - Lectin-mediated mucosal delivery of drugs and microparticles.
AB  - Absorption of drugs and vaccines at mucosal surfaces may be enhanced by
      conjugation to appropriate bioadhesins which bind to mucosal epithelia.
      Bioadhesins might also permit cell- and site-selective targeting. One approach is
      to exploit surface carbohydrates on mucosal epithelial cells for lectin-mediated
      delivery. We review work supporting the use of lectins as mucosal bioadhesins in
      the gastrointestinal and respiratory tracts, the oral cavity and the eye. The
      gastrointestinal tract is particularly favoured for mucosal delivery. Many
      studies have demonstrated that the antigen sampling intestinal M cells offer a
      portal for absorption of colloidal delivery vehicles. Evidence is presented that
      M cell targeting may be achieved using M cell-specific lectins, microbial
      adhesins or immunoglobulins. While many hurdles must be overcome before mucosal
      bioadhesins can guarantee consistent, safe, effective mucosal delivery, this is
      an exciting area of research that has important implications for future drug and
      vaccine formulation.

PMID- 10967228
TI  - Endogenous lectins as targets for drug delivery.
AB  - To minimize side effects of drugs it would be ideal to target them exclusively to
      those cell types which require treatment. As a means to this end prototypical
      cellular recognition systems pique our interest to devise biomimetic strategies.
      Since oligosaccharides of glycoconjugates outmatch other information-carrying
      biomolecules (proteins, nucleic acids) in theoretical storage capacity by far,
      work on the sugar code can spark off development of effective targeting devices.
      Conjugation of custom-made glycan epitopes to proteins or biocompatible non
      immunogenic polymeric scaffolds produces neoglycoconjugates with purpose
      adaptable properties. In the interplay with endogenous receptors such as lectins,
      suitable oligosaccharides such as histo-blood group trisaccharides as parts of
      neoglycoconjugates have already proven their practical applications in
      histopathology. Elucidation of the structure of cell lectins with currently five
      main families aids to tailor ligand characteristics rationally. They include the
      types of functional groups and their topological presentation to optimize the
      bimolecular binding as well as the optimal spatial clustering and spacer
      characteristics to exploit cooperativity. Indeed, the potent trivalent cluster
      glycosides designed for the C-type asialoglycoprotein receptors furnish an
      instructive example how to turn the theoretical guideline on ligand modification
      into nM-affinity. By placing emphasis on tissue lectins as targets of
      neoglycoconjugate-mediated drug delivery, the long-term perspective is opened to
      likewise test members of these families themselves for routing of therapeutic
      payloads, aiming at cell addressins. This review illustrates the conceivable
      potential which work on the sugar code with custom-made neoglycoconjugates and
      tissue lectins can have in store for drug delivery.

PMID- 10967229
TI  - Experimental manipulation of a unique cue in Pavlovian SCR conditioning with
      humans.
AB  - We report two experiments on positive and negative patterning in human skin
      conductance response (SCR) conditioning with a manipulable unique cue. In
      experiment 1 flashing red lights, arrayed horizontally, were used as elements and
      apparent movement was used as additional (unique) cue when the elements were
      presented in compound. Positive and negative patternings were both acquired
      readily, and positive patterning transferred to new stimuli (green lights,
      vertically arrayed). The unique cue did not influence these outcomes. Experiment
      2 examined only positive patterning, using a more conventional unique cue, a
      visual frame that surrounded the letter stimuli on compound trials but not on
      element trials. The unique cue again facilitated neither acquisition nor
      transfer. These results do not support either the unique cue extension of the
      Rescorla-Wagner theory or configural theories. Human participants seem to utilize
      'size' or 'number' or some other abstract feature in preference to available
      concrete stimuli.

PMID- 10967230
TI  - Neuro-cognitive activity during a self-paced visuospatial task: comparative EEG
      profiles in marksmen and novice shooters.
AB  - Log-transformed EEG power spectral estimates (6-7, 9,10-11,18-22, and 36-44 Hz),
      obtained from skilled marksmen and novice shooters at sites F3, F4, C3, C4,T3,
      T4, P3, P4, O1, and O2 during the aiming period (6 s) of a target shooting task
      for each of 40 trials up to the moment of trigger pull, were contrasted to
      determine regional differences in cortical activation. The EEG power obtained
      from both groups during the preparatory aiming period was also compared to that
      observed for a similar time period during the processing of standard verbal and
      spatial tasks. The marksmen exhibited less activation than the novice shooters at
      all sites during the aiming period with a pronounced difference in the left
      central-temporal-parietal area. Fewer group differences in cortical activation
      were observed during the comparative verbal and spatial tasks with which the
      groups held equal experience. Additionally, the novice shooters exhibited a
      cortical activation pattern during target shooting that was similar to that
      observed during the processing of the comparative verbal and spatial tasks. In
      contrast, marksmen generally exhibited less cortical activation during the aiming
      period when contrasted to that during the novel comparative tasks. These results
      are consistent with the notion of relative economy in the cortical processes of
      marksmen, relative to controls, during the specific challenge with which they are
      highly practiced.

PMID- 10967231
TI  - Habituation and laterality of orienting processes as reflected by slow negative
      waves.
AB  - The study is concerned with the question of whether the orienting wave (O-wave),
      a slow potential shift of the event-related brain potential, is a component of
      the orienting response (OR). As habituation is supposed to be the most important
      characteristic of the OR, we focussed particularly on any habituating aspect of
      the O-wave. Results suggest that its bilateral distribution over midfrontal areas
      might constitute such a link relating the O-wave to orienting activity.
      Hemispheric asymmetry linearly decreased its right-sided predominance in response
      to repeated presentations of an initially novel auditory stimulus. A similar,
      concomitant diminution of the skin conductance response (SCR) occurred. Both, the
      O-wave and the SCR varied, moreover, with signal value and electrodermal lability
      which are known to relate to the OR. Therefore we suggest the O-wave comprise
      features typical of a component of the OR. A hypothesis is put forward according
      to which the O-wave and its laterality are dependent on the ascending
      noradrenergic locus coeruleus system.

PMID- 10967232
TI  - Operant conditioning of left-hemispheric slow cortical potentials and its effect
      on word processing.
AB  - This study investigated whether language-related cognitive processes can be
      modified by learned modulation of cortical activity. Study participants received
      feedback of slow cortical potentials (SCPs) recorded above left-hemispheric
      language cortices and were reinforced for producing negative and positive shifts
      upon two different discriminative stimuli. In all subjects who achieved reliable
      control of left-hemispheric brain responses, substantial modification of word
      processing was observed. Behavioral modification could be documented in two
      experiments in which word probes were presented following discriminative stimuli.
      When negative shifts of the EEG were required, lexical decisions on words were
      substantially speeded, while they were slowed during positivity conditions. There
      was no indication for any performance difference between conditions in control
      subjects who failed to achieve control over SCPs after feedback training. This
      result was replicated in an experiment using lateralized-tachistoscopic stimulus
      presentation. Comparisons of word and pseudoword responses in both experiments
      indicated that behavioral modification was most pronounced for word responses. It
      was also not seen in a simple reaction time task not involving language
      materials. This argues against a global effect related to perception, visuo
      spatial attention, or motor processes. We conclude that linguistic processes can
      be influenced by modification of cortical activity due to operant conditioning.
      In closing, tentative explanations of the present results based on theories of
      language and attention processes are being discussed.

PMID- 10967234
TI  - Hyperventilation and attention: effects of hypocapnia on performance in a stroop
      task.
AB  - This study aimed to investigate the effect of hypocapnia on attentional
      performance. Hyperventilation, producing hypocapnia, is associated with
      physiological changes in the brain and with subjective symptoms of dizziness,
      concentration problems and derealization. In this study (N=42), we examined
      cognitive performance on a Stroop-like task, following either 3 min of hypocapnic
      or normocapnic overbreathing. Both overbreathing trials were run on separate
      days, each preceded by a baseline trial with the same task during normal
      breathing. More and other symptoms were reported after hypocapnia compared to
      normocapnia. Also, more errors were made and progressively slower reaction times
      (RT's) were observed during recovery from hypocapnia. These performance deficits
      were only found in participants characterized by apneas. The number of symptoms
      did not correlate with RT's or errors. The pattern of data suggested that
      hypoxia, as a result of apneas during recovery from hypocapnia, caused the
      cognitive performance deficit.

PMID- 10967233
TI  - Cardiopulmonary baroreflex stimulation and blood pressure-related hypoalgesia.
AB  - Results from both experimental animals and humans suggest that baroreflex
      stimulation may be involved in blood pressure-related hypoalgesia. However, most
      of this research, especially in the area of human experimentation, has focused on
      sinoaortic baroreceptors. Cardiopulmonary baroreflex stimulation may also be an
      important moderator of pain. Sixty-six healthy male undergraduates varying in
      risk for hypertension participated in an experimental protocol in which painful
      mechanical finger pressure was presented three times in a counterbalanced
      fashion. One pain stimulus was preceded by 6 min of supine rest, another by a
      period of rest interspersed with periodic Valsalva manoeuvres, and another by a
      period in which cardiopulmonary baroreceptors were stimulated by passive leg
      elevation. Significantly lower pain was reported by men with relatively elevated
      systolic blood pressure following leg elevation but not the other conditions.
      Cardiopulmonary baroreflex stimulation was documented by increased forearm blood
      flow and other data obtained via impedance cardiography. These results suggest
      that blood pressure related hypoalgesia may be at least partially related to
      cardiopulmonary baroreflex stimulation.

PMID- 10967235
TI  - The time course of spatial orienting elicited by central and peripheral cues:
      evidence from event-related brain potentials.
AB  - To study differences in the time course of attentional orienting triggered by
      salient peripheral events and by central symbolic precues, event-related brain
      potentials (ERPs) were recorded in response to letter stimuli following spatially
      informative symbolic or peripheral precues after a cue-target interval (CTI) of
      either 200 or 700 ms. Stimuli at cued (attended) locations elicited an enhanced
      negativity relative to stimuli at uncued locations. With short CTIs, these
      effects started around 150 ms post-stimulus for peripheral cues. They were
      delayed by about 100 ms for central cues. This latency difference is assumed to
      reflect fast exogenous orienting elicited by peripheral, but not by central cues.
      Beyond 200 ms post-stimulus, attentional negativities were larger with long CTIs
      than with short CTIs for both cue types, presumably related to the gradual build
      up of endogenous orienting triggered by spatially predictive events.

PMID- 10967236
TI  - Influence of bull biostimulation, season and parity on resumption of ovarian
      activity of zebu (Bos indicus) cattle following parturition.
AB  - A total of 135 postpartum suckled zebu cows were assigned randomly at calving to
      two treatments: cows exposed to vasectomised bulls (Mature Bull Exposure, MBE)
      and cows not exposed to bulls (No Bull Exposure, NBE) for a period of 150 days
      postpartum. This study was conducted to determine the influence of bull
      biostimulation, season and parity on postpartum reproductive performance of Bos
      indicus cattle. The trials were conducted in two seasons: cows calving in the dry
      season and cows calving in the rainy season. Cows with an increase in serum
      progesterone (P(4)) concentration of >1 ng/ml from the weekly blood samples were
      used to analyse the number of days from calving to the time of resumption of
      ovarian activity. The introduction of vasectomised bulls shortened the postpartum
      anoestrus in cattle following calving. Mean interval from calving to resumption
      of ovarian activity for the MBE cows was 71.7 days, which was significantly
      earlier following calving than the NBE cows with a duration of 77.8 days. By 60
      to 80 days postpartum, the proportion of cows at resumption of postpartum
      activity for MBE cows was greater than for the NBE cows. Mean interval from
      calving to resumption of ovarian activity for cows that calved in the dry season
      was 71.3 days, which was significantly earlier than for cows that calved in the
      rainy season (78.6 days). At 60 days postpartum, the proportion of cows at
      resumption of postpartum ovarin activity for cows that calved in the dry season
      was greater than the cows that calved in the rainy season. Mean interval from
      parturition to resumption of ovarian activity for cows with three to five
      calvings was 65.1 days, which was significantly earlier than the value of 71. 2
      days for cows with one to two calvings. By 60 to 80 days postpartum, the
      proportion of cows at onset of ovarian activity for cows with three to five
      calvings was greater than those cows with one to two calvings. Cows that calved
      in the dry season completed uterine involution by 24.4 days, which was
      significantly shorter than the duration of 26.5 days for cows that calved in the
      rainy season. Cows with three to five calvings completed uterine involution
      earlier than those with one to two calvings. It is concluded that bull-cow
      biostimulation influences reproductive activity in the cow possibly through
      olfactory cues (pheromones).

PMID- 10967237
TI  - Hormonal and ovarian responses to a 5-day progesterone treatment in anoestrous
      dairy cows in the third week post-partum.
AB  - Primiparous cows with low body condition at calving have an extended anovulatory
      period. Induction of ovulation and oestrus is possible with progesterone
      treatment but the response to this treatment differs between Friesian and Jersey
      breeds. The objective of this study was to describe changes in pulsatile LH
      secretion and the synchrony of developing ovarian follicles that occur during a
      progesterone treatment period of 5 days in primiparous anovulatory cows. The
      experimental model compared the progesterone treatment with spontaneous post
      partum changes as well as a breed comparison in a factorial design.Thirty-six
      cows (Jersey n=19 and Friesian n=17) were managed to calve with a low body
      condition score (BCS<4. 5). Daily changes in ovarian follicle size were observed
      with transrectal ultrasonography in each cow from 8 days post-partum. Thirty of
      these cows were diagnosed to be anovulatory at 12-18 days post-partum (day 0) and
      allocated to a treatment (n=16) or a control group (n=14), balanced for breed.
      Each treated cow had a progesterone-releasing controlled internal drug-releasing
      (CIDR) device inserted vaginally for 5 days while control cows were left
      untreated. Changes in plasma LH concentrations were measured with intensive blood
      sampling over 8 h on days -1, 1, and 4. Blood samples were also collected daily
      (06:00 h) for determination of plasma progesterone as well as oestradiol
      concentrations on days 6 and 8. Treatment with progesterone was associated with a
      transient initial decrease (day 1) in both LH pulse frequency and mean LH
      concentrations after device insertion, but both had returned to pre-treatment
      levels by day 4. Jersey cows had a greater pulse frequency, but there was no
      breed difference in mean LH concentrations. Patterns of ovarian follicle growth
      were affected by progesterone treatment with an increase in diameter of the
      dominant follicle (DF) identified after treatment initiation. This followed an
      earlier emergence of a new DF after device insertion. Follicular response to
      progesterone was dependent on the diameter of the DF present at treatment
      initiation. Those follicles >/=9 mm were replaced by a new DF during treatment
      such that the DF observed at the time of device removal was large (>/=9 mm) and
      growing in 13/16 cases.Progesterone was not effective for the induction of an LH
      surge, ovulation and oestrus in anovulatory cows with a low BCS. However,
      treatment was associated with synchronous development of a DF so that it was
      large and growing at the end of the treatment period in most cases. This
      synchronous development may be due to the transient suppression of LH and the
      presence of an LH-dependent DF.

PMID- 10967238
TI  - In vitro culture of bovine preantral follicles.
AB  - Bovine preantral follicles (40-100 microm diameter at collection) were collected
      from ovaries of slaughtered cows and cultured in vitro with one of the four
      treatments: follicle stimulating hormone (FSH; 100 ng/ml) alone; FSH plus
      epidermal growth factor (EGF; 100 ng/ml); FSH plus insulin-transferrin-selenium
      (ITS; +1%) or FSH plus hypoxanthine (4 mM) in tissue culture medium (TCM 199)
      supplemented with 10% fetal calf serum (FCS), 0.1 mg/ml sodium pyruvate, 100
      IU/ml of penicillin and 100 microg/ml streptomycin. The control culture medium
      was TCM 199 with supplements without any treatments. Follicles of each size were
      cultured separately in groups of one to three in 24-well multidishes each
      containing 500 microl of the appropriate culture medium. Culture commenced at
      follicle recovery (day 1) and continued for 10 days (harvested on day 11). In
      each case, half the medium was removed and replaced by fresh medium every third
      day. Follicle diameters were recorded on days 1, 5 and 11 of the experiment. At
      the end of the 10-day culture period, half of the follicles were stained with
      trypan blue to assess their potential viability and half were stained with
      bisbenzimide plus propidium iodine to estimate various morphological features of
      the follicles. Follicles of all initial sizes, on all culture treatments,
      increased in diameter during in vitro cultures with the greatest increases, both
      in absolute and proportional size, occurring between days 1 and 5 of culture. All
      of the culture medium supplements caused greater increases in follicle diameters
      than control medium at both days 5 and 11 of culture for all initial sizes of
      follicles (p<0.01). The most effective culture supplements for follicles of 40-,
      60- and 80-microm initial diameter were FSH alone and FSH+EGF. The size of these
      follicles at both days 5 and 11 of culture on both the treatments was
      significantly larger (p<0.01) than follicles cultured in the presence of the
      other two supplementary treatments. The growth of follicles of 100-microm initial
      diameter did not differ between culture medium supplements. None of the culture
      media caused follicle size to increase to the initial diameters of the next
      larger size category during the 10 days of culture although follicles of 100
      microm diameter achieved a diameter of 120 microm, after 4 days of culture. The
      overall follicular viability and morphology were better with treatments than the
      controls in all cases; however, there was no significant difference (p>0.05)
      among them. From this experiment, FSH and FSH plus EGF may be recommended for in
      vitro culture of smaller (40, 60 and 80 microm) follicles.

PMID- 10967239
TI  - Serum progesterone profiles of zebu cattle (Bos indicus) in relationship to
      conception and repeat breeding after artificial insemination.
AB  - Sixty-four zebu cows, comprised mainly of Bunaji cattle aged between 3 and 7
      years old, were involved in an intensive artificial insemination programme. The
      study was conducted during the breeding period (May-October), and cows were
      inseminated with freshly prepared Friesian semen when they stood to be mounted by
      the vasectomised bull or herdmates. Fertility was measured by serum progesterone
      (P(4)) concentrations and pregnancy diagnosis by rectal examination post
      insemination. From the records of oestrus detection and P(4) profiles of cattle
      following breeding, 39 oestrous cycle lengths were classified into short, normal
      and long cycles. The mean duration for short, normal and long oestrous cycles
      were 15.6+/-2.0, 21.5+/-1.5 and 29.5+/-2.5 days, respectively. Mean inter-oestrus
      intervals between the treatment groups were not different. The percentage
      frequency distribution was 48.7% for normal oestrous cycles. The short oestrous
      cycle lengths of 11-17 days were observed in 12.8% of the cases, while 38.5% of
      the cases of oestrus returns had long luteal phases with oestrous cycle lengths
      of 26-32 days. Out of the 64 cows, 48.4% conceived to the first breeding while
      18.8% conceived to the second breeding. Five and nine cows became acyclic after
      the first and second breeding, respectively, constituting 22. 0%. Cows that
      displayed irregular oestrous cycles (repeat breeders) constituted 10.9%. Average
      number of services per conception was 1.3. Serum P(4) is of practical value in
      monitoring ovarian activity in cattle and in the identification of acyclic and
      repeat breeder cows. Repeat breeder cows could be investigated by a combination
      of radioimmunoassay and clinical examination of the ovaries and reproductive
      tract. In cattle management, it is economical and profitable to diagnose
      pregnancy early after insemination so that cows which fail to conceive may be
      rebred.

PMID- 10967240
TI  - Blastocyst viability and generation of transgenic cattle following freezing of in
      vitro produced, DNA-injected embryos.
AB  - This study examined whether the viability, determined in vitro, of DNA-injected
      bovine embryos produced in vitro was affected by freezing, and if the frozen
      embryos developed to term following transfer to recipients. In vitro fertilized
      zygotes were injected with the pBL1 gene and then co-cultured with mouse
      embryonic fibroblasts (MEF) in CR1aa medium. Embryos were prepared for
      cryopreservation by exposure to a 10% (v/v) glycerol solution, loaded into 0.25
      ml straws and then frozen by conventional slow freezing. Thawing was by rapid
      warming in water (37 degrees C) and embryos were rehydrated in PBS diluents of
      6%, 3% and 0% (v/v) glycerol supplemented with 0.25 M sucrose and 0.5% (w/v) BSA.
      In Experiment 1, blastocysts that developed from DNA-injected embryos were
      individually classified into three morphological groups and three stages of
      development prior to freezing. DNA-injected blastocysts of excellent quality at
      freezing showed a higher survival rate (78.8+/-10.6%) after thawing than those of
      good (60. 9+/-16.4%) or fair (12.5+/-5.9%) quality (P<0.05). Post-thaw survival
      rate, judged in vitro, increased with more advanced stage of blastocyst
      development at freezing (early 48.8+/-15.9%, mid 52. 1+/-12.6% and expanded
      71.2+/-1.1; P<0.05). In Experiment 2, the frozen/thawed embryos were transferred
      to recipients to examine in vivo viability. Following transfer of one or two
      embryos per recipient, pregnancy rates at 60 days of gestation were 13.6% (13/96)
      for frozen embryos and 26.5% (43/162) for fresh embryos (P<0. 05). Of the 12 live
      calves born from the frozen/thawed embryos, two males (18.3%) were transgenic.
      None of the live-born calves derived from fresh embryos exhibited the transgene.
      One of transgenic bulls did not produce transgenic sperm. Three out of 23 calves
      (13.0%) produced from cows inseminated with semen of the other bull were
      transgenic, suggesting that this animal was a germ-line mosaic. These studies
      indicated that the viability of in vitro produced, DNA-injected bovine
      blastocysts was affected by freezing and by both the quality and stage of
      development of the embryo prior to freezing. The generation of transgenic cattle
      demonstrates that it is feasible to freeze DNA-injected, in vitro produced
      embryos.

PMID- 10967241
TI  - Effect of ACTH-challenge on progesterone and cortisol levels in ovariectomised
      repeat breeder heifers.
AB  - In order to investigate the potential influence of stress as a component of the
      repeat breeding syndrome, the adrenocortical capacity for steroid production was
      evaluated in ovariectomised dairy heifers. In repeat breeder heifers (RBH),
      marginally elevated plasma progesterone levels during oestrus, so-called
      suprabasal progesterone levels, have earlier been measured and are believed to
      impair fertility. The aim was to distinguish if this progesterone could be of
      extra-gonadal or in this case, adrenal origin. Baseline levels of plasma cortisol
      and progesterone were determined as well as the corresponding response after
      induced acute stress in the form of an adrenocorticotropin (ACTH)-challenge.
      Comparisons were made between strictly selected RBH, n=5 and virgin heifers (VH),
      n=5 of the Swedish Red and White breed. The heifers were used as their own pre
      challenge controls in a 2-day trial. On the control day, saline was injected i.v.
      and on the treatment day, a synthetic analogue of ACTH (60 microg Synachten(R)).
      Via a jugular vein catheter, blood samples were collected every 30 min for 6 h
      each day of the experiment. Analyses for plasma progesterone and cortisol were
      made. RBH had a significantly higher (P<0.01) pretreatment baseline cortisol
      level (10.1+/-2.3 nmol l(-1)) than VH (2.6+/-0.2 nmol l(-1)). Moreover, the
      cortisol response after stimuli was stronger in RBH than VH, especially
      concerning total hormone production (P<0. 001), but there was also a tendency
      towards higher peak values (P=0. 06) and longer duration of significantly
      increased hormone concentrations (P=0.08). Progesterone concentrations, however,
      did not differ between the groups. Both baseline levels (P=0.25) and
      posttreatment production (P=0.45) were of the same magnitude in RBH and VH. In
      conclusion, the study could not confirm that suprabasal progesterone
      concentrations during oestrus in RBH derive from the adrenal glands. Still,
      apparent differences were found in adrenocortical activity when ovariectomised
      heifers, VH and RBH, were subjected to an ACTH-challenge. It is suggested that a
      sustained adrenal stimulation associated with environmental or social stress
      could be one factor in the repeat breeding syndrome.

PMID- 10967242
TI  - Pre-ovulatory follicular characteristics and ovulation rates in different breed
      crosses, carriers or non-carriers of the Booroola or Cambridge fecundity gene.
AB  - Terminal follicular dynamics and ovulation rates (OR) were compared in different
      local breeds after introducing fecundity genes of different origin. Crossbred
      ewes which were carriers (F+) or non-carriers (++) of Booroola (BFec) or
      Cambridge genes (CFec) were included: CambridgexCambridge (CC), CambridgexSuffolk
      (CS), CambridgexTexel (CT), BooroolaxTexel (BT) and BooroolaxGerman Mutton Merino
      (BGM). The numbers of small (diameter 2-3.5 mm), medium (diameter >3.5-5.0 mm)
      and large (diameter >5.0 mm) growing follicles, the maximum diameter before
      ovulation and the regression and artesia rates of ovarian follicles >/=2 mm in
      diameter were studied laparoscopically and repeatedly during the last 5 days of
      an induced oestrous cycle. The ORs were determined one cycle before and two
      cycles after the repeated laparoscopy. BFec and CFec significantly enhanced the
      OR of all crossbreeds. Carriers of BFec or CFec did not have significantly
      different ORs due to any crossbreeding effect. The same observation was made for
      non-carriers of both Fec gene types. Whatever the crossbreed, the number of
      small, medium and large growing follicles were similar between carriers and non
      carriers in spite of a higher number of ovulating follicles in carriers of both
      Fec gene types. The diameter of ovulatory follicles did not differ among
      crossbreds, or between carriers and non-carriers except in the BT (5.2+/-0.2 vs.
      6.5+/-0.8 mm, respectively) and CC (6.6+/-0.2 vs. 5.6+/-0.3 mm) ewes.The higher
      OR in the presence of the Booroola gene was associated with a low atresia rate of
      large follicles in all crossbreeds (BT: 52+/-8% (F+) vs. 61+/-7% (++); BGM: 51+/
      6% vs. 75+/-5%). The high OR of the carriers of the CFec gene seemed to be
      associated with a lower number of large growing follicles with a lower (P<0.05)
      atresia rate as compared with Booroola crossbreeds. In conclusion, follicular
      features were similar between purebred Cambridge and its crossbred CS and CT. In
      ewes carrying the BFec or CFec gene, the reduction in follicular atresia seemed
      to be one of the main follicular features implicated in the higher OR.

PMID- 10967243
TI  - Release of oxytocin and prostaglandin f(2alpha) around teasing, natural service
      and associated events in the mare.
AB  - Mating has been shown in many species to provoke the release of oxytocin (OT). In
      our study, various stimuli were applied to mares to study release of OT and
      prostaglandin F(2alpha) (PGF(2alpha)) associated with mating. Blood samples were
      collected from mares around the time of teasing both in oestrus and dioestrus and
      at mating. For comparison, blood samples were also collected at the time of
      manual manipulation of the genital tract and after intrauterine infusion of 500
      ml phosphate buffered saline (PBS). Additional samples were collected 16 to 18 h
      after mating. Mating caused a significant increase in OT in all mares and teasing
      caused a significant OT response in 6 of 10 oestrous and 3 of 5 dioestrous mares.
      However, mating and teasing had no significant effect on concentrations of 15
      keto-13,14-dihydro-PGF(2alpha) (PGFM). Manual manipulation of the clitoris,
      vagina and cervix caused significant OT release in all mares and intrauterine
      infusion of 500 ml PBS caused significant OT release in three of the five mares.
      However, only one mare had a significant PGF(2alpha) response during manual
      manipulation and only one responded positively to intrauterine infusion of 500 ml
      PBS. We concluded that events around mating, including stimulation of the genital
      tract and uterine distension, often caused an increase in circulating
      concentrations of OT but only rarely in PGFM.

PMID- 10967244
TI  - Activation of pig oocytes using calcium ionophore: effect of protein synthesis
      inhibitor cycloheximide.
AB  - In vitro matured pig oocytes were activated using a combined treatment of calcium
      ionophore A 23187 with cycloheximide. The oocytes were exposed to ionophore (10,
      25 or 50 microM) for 0.5, 1, 3, 5 or 7 min and then cultured with cycloheximide
      (0 or 10 microg/ml) for 6 h. Cycloheximide treatment significantly increased the
      activation rate of oocytes and the percentage of oocytes that were able to
      develop after activation. The highest activation rate was observed after
      treatment with 50 microM ionophore. The highest percentage of developing eggs was
      observed after combined treatment of ionophore (25 microM) with cycloheximide.
      The percentage of oocytes developing up to the morula and blastocyst stage was
      not significantly increased after cycloheximide treatment.

PMID- 10967245
TI  - Co-injection of restriction enzyme with foreign DNA into the pronucleus for
      elevating production efficiencies of transgenic animals.
AB  - The microinjection method for production of transgenic farm animals requires
      specialized techniques and results in intolerably low production efficiencies. We
      investigated whether or not co-injection of foreign DNA constructs with
      restriction endonuclease into the pronucleus of mouse zygotes would improve the
      integration frequencies of foreign DNA into the host genome. Two kinds of DNA
      constructs that have no EcoRI site in their sequences were used for co
      microinjection. With reference to the results of experiments in which EcoRI alone
      was injected at various amounts varying from 10(-9) to 10(-5) U/nucleus, the
      amount of 5x10(-8) U/nucleus that showed survival rate of 60.6% was used for the
      co-injection with DNA. Successful transgenesis of co-injected embryos was
      identified by DpnI-Bal31 digestion method for single embryos and by PCR method
      for pups born, respectively. The overall efficiency for the integration of
      foreign DNA in single embryos and live-born pups obtained by the co-injection
      procedures were 17.9% compared with 9.1% obtained by the injection of DNA alone.
      The results suggest that co-injection of foreign genes with restriction enzyme
      may elevate the integration rate of foreign genes into host genomes.

PMID- 10967246
TI  - Erratum to "Short-term dietary effects on reproductive wastage after induced
      ovulation and artificial insemination in primiparous lactating sarda ewes"

PMID- 10967247
TI  - Motherless case in paternity testing.
AB  - In paternity test using the DNA evidence, the analysis of the deficient case that
      the DNA profiles of mother or alleged father are not available is different from
      that of the trio case analyzed routinely. However, the motherless case that the
      genotypes of mother is not available has been requested and analyzed like the
      trio case. In this paper, we compared the motherless case and the trio case
      through the mean exclusion chance describing the probability of exclusion for a
      genetic marker system and the distribution of the probability of paternity
      calculated using the three current methods. We have also shown a case which can
      be falsely discriminated if it were requested in the analysis of the motherless
      case, and conclude that the analysis of the motherless case should be carefully
      conducted and the level for the discrimination should be different from that of
      the trio case.

PMID- 10967248
TI  - Heroin impurity profiling. A harmonization study for retrospective comparisons.
AB  - Three laboratories present a harmonised system for the retrospective comparison
      of south west Asian heroin. It consists of an improved gas chromatographic (GC)
      profiling method and a computerised data retrieval. The investigations of the GC
      were necessary with a view to improve the reproducibility of the system. The
      necessity of a strict quality control is emphasized. The peaks of the GC profile
      were investigated for abundance, intensity, GC behaviour (reproducibility) and
      correlations; 16 of them were selected for describing the heroin profile in the
      database. The results from intra-lab profile comparisons are reported. The
      reproducibility of the analysis was good and the variation between the samples
      was large, thus, allowing conclusions with a high degree of certainty. The
      criteria of similarity were defined. The system is successfully running in all
      three labs. In connection with inter-laboratory comparison, the aspects of method
      harmonisation and standardisation are discussed. It appeared that the GC method
      is a very subtile one, urging for a strict standardisation between the three
      labs. Despite a long cooperation between three well-equipped and experienced
      labs, a more or less serious loss of reproducibility was noticed in the inter-lab
      results in comparison with the intra-lab results. The loss could for the greater
      part be attributed to the (limits of the) GC technique; a number of compounds,
      necessary for making the discrimination between samples, showed difficult
      chromatographic behaviour, leading to insufficient inter-lab reproducibility.
      Using the actual variables, improvements in performance can hardly be expected in
      the near future. The loss of reproducibilty implies that the number of false
      positive matches in a database search increases. This may strongly reduce the
      value of a relatively large, international database. The study shows that so far,
      the best option for international comparison is the analysis in a central
      laboratory. The idea of local determination at a large number of national labs
      and the use of a common database is not a realistic aim for this type of
      analysis.

PMID- 10967249
TI  - Metal concentrations in plants and urine from patients treated with traditional
      remedies.
AB  - A number of traditional South African herbal remedies which are associated with
      morbidity and mortality were analysed for selenium, manganese, copper, lead, zinc
      and mercury content. Few showed high levels of toxic metals, but in these the
      concentrations were sufficiently high as to cause concern since there is no
      quality control on the production of these remedies, which are the accepted form
      of medication for over 80% of the population. Urine samples, obtained from 65
      patients admitted to hospital following treatment with a traditional herbal
      remedy were also analysed for metals. Only a small number of the patients had
      abnormally high levels of metal excretion. These data suggest that, in contrast
      to experience with traditional Chinese and Indian preparations, metal
      contamination from plants seems not to be a problem in traditional South African
      remedies.

PMID- 10967250
TI  - An anatomical and photographic technique for forensic facial identification.
AB  - The increase in the use of photographs on individual identification credentials
      such as driving licences, credit cards, security passes and passports has led,
      for the purpose of criminal activities, to the falsification of genuine documents
      bearing photographs of the perpetrating criminal. These photographs may be used
      as valuable physical evidence when compared with known photographs of a suspect
      as they form somewhat of a signature of the suspect that is left behind on the
      evidence. The comparison of ID photographs requires the cooperation of two
      predominantly visual disciplines; forensic photography and morphological anatomy.
      This paper describes a photographic technique which allows accurate anatomical
      measurement and tracing of facial features, which allows direct physical
      comparison of ID document images.

PMID- 10967251
TI  - Relatedness testing in subdivided populations.
AB  - Assigning probabilities to alleged relationships, given DNA profiles, requires,
      among other things, calculation of a likelihood ratio (LR). Such calculations
      usually assume independence of genes: this assumption is not appropriate when the
      tested individuals share recent ancestry due to population substructure. Adjusted
      LR formulae, incorporating the coancestry coefficient F(ST), are presented here
      for various two-person relationships, and the issue of mutations in parentage
      testing is also addressed.

PMID- 10967252
TI  - Comparison of the clinical and post mortem diagnoses of the causes of death.
AB  - The fast moving progress in medical technology causes someone to ask if the
      progress is not only in diagnostic abilities but also in diagnostic precision.
      Despite the improved quality of diagnostic technology, the frequency of
      misdiagnosis has not decreased appreciably. The goal of autopsy is not only to
      uncover clinicians mistakes or judge them but rather to instruct clinicians to
      learn by their own mistakes. We reviewed the autopsy records from the Archive of
      the Institute of Forensic Medicine in Ljubljana of 1792 deceased persons in 1997
      and 1998 and compared the clinical and post mortem diagnoses. We eliminated from
      study all autopsies performed on deceased persons not admitted to the Clinical
      Medical Centre. From the remaining 911 autopsy reports we compared the post
      mortem diagnoses with the clinical diagnoses. We classified findings into five
      groups according to the level of agreement between the clinical and the post
      mortem diagnoses. Group 1 included cases of complete agreement between clinical
      and post mortem diagnoses. Group 2 cases of disagreement about the basic illness,
      group 3 cases of partial disagreement about the direct causes of death, group 4
      cases of total disagreement between the clinical diagnosis and the post mortem,
      named, also misdiagnosis and group 5 clinical diagnosis which could not be
      calssified. The diagnoses were in total agreement in 49.30% of cases, in partial
      agreement (disagreement about direct causes of death) in 20.68% and in
      disagreement about the basic illness in 6.87%. The diagnoses were in total
      disagreement in 9.87%. 13.30% of cases were not possible to classify owing to
      incomplete death certificates or reports of the causes of death.

PMID- 10967253
TI  - Release of monocyte chemoattractant protein (MCP)-1 by a human alveolar
      epithelial cell line in response to mycobacterium avium.
AB  - Clinical strains of Mycobacterium avium isolated from patients with acquired
      immunodeficiency syndrome, but not a non-clinical laboratory strain (ATCC 25291),
      were found to stimulate the human alveolar epithelial cell line A549, to produce
      monocyte chemoattractant protein (MCP)-1. A549 cells were also found to produce
      elevated levels of MCP-1 in response to sonicates of the clinical strains of M.
      avium, and surprisingly, the non-clinical strain as well. However, sonic extracts
      of the clinical strains were found to induce significantly higher levels of MCP-1
      production compared to extracts of the non-clinical strain (P < 0.001). These
      data suggest the existence of strain-related differences in antigen expression by
      M. avium. The clinical and non-clinical strains of M. avium were found to attach
      and invade, but not replicate in A549 cells indicating that MCP-1 production by
      A549 cells does require the presence of viable, replicating organisms. Activation
      of alveolar epithelial cells by exposure to M. avium resulting in the production
      of chemokines which recruit inflammatory cells to the site of infection may be an
      important regulatory pathway for the activation of pulmonary host defense.

PMID- 10967254
TI  - Genotypes of multidrug-resistant Salmonella enterica serotype typhimurium from
      two regions of Kenya.
AB  - A combination of phage typing and pulsed-field gel electrophoresis of Xbal
      digested chromosomal DNA has been used to study the epidemiological relationships
      of multidrug-resistant Salmonella enterica serotype typhimurium from Nairobi (64
      isolates) and Kilifi (40 isolates) collected over the period 1994-1997. Isolates
      from Nairobi belonged to 11 definitive phage types (DTs) encompassing eight
      different PFGE patterns. In contrast, isolates from Kilifi were mainly DT 56
      (60%) and all fell into a single PFGE pattern. The remaining isolates did not
      conform to a recognisable phage type. We conclude that multidrug-resistant S.
      typhimurium infections from Nairobi were caused by multiple strains while those
      from Kilifi were likely to be from a microepidemic caused by a single clone.

PMID- 10967255
TI  - Specific immune response to a synthetic peptide derived from outer surface
      protein C of Borrelia burgdorferi predicts protective borreliacidal antibodies.
AB  - In a previous study, we described the development of a new specific
      serodiagnostic test for Lyme disease involving enzyme-linked immunosorbent assay
      and a synthetic peptide, OspC-I. The OspC-I peptide is derived from part of the
      outer surface protein C (OspC) amino acid sequence of Borrelia burgdorferi and is
      located in the region conserved among B. burgdorferi sensu stricto or sensu lato
      isolates. In this study, we demonstrate that sera containing antibodies against
      OspC-I from patients with early Lyme disease had borreliacidal activity against
      isolates of three genospecies of Lyme disease spirochete, B. burgdoreferi B31, B.
      garinii HPI and B. afzelii HT61. However, the borreliacidal activity against B.
      burgdorferi, which has not been isolated in Japan, was weaker than that against
      the other species. Vaccination of mice with OspC-I induced the production of anti
      OspC-I antibodies in serum with borreliacidal activity. The immune mouse serum
      had significantly higher levels of borreliacidal activity against HP1 and HT61,
      than against B31. Neutralization of borreliacidal activity with anti-IgM
      antibodies showed that the borreliacidal activity of anti-OspC-I antibodies in
      serum was due to IgM. Furthermore. mice vaccinated with OspC-I were protected
      against challenge with HPI and HT61. but not fully protected against infection
      with B31. These results suggest that OspC-I is not only a specific antigen for
      use in serodiagnostic tests for Lyme disease, but is also a potential candidate
      for a Lyme disease vaccine in Japan.

PMID- 10967256
TI  - Helicobacter pylori infection of human gastric epithelial cells induces IL-8 and
      TNFalpha, but not TGFbeta1 mRNA.
AB  - Helicobacter pylori (Hp) infection causes gastric ulcers and gastric carcinomas.
      The mechanisms of these diseases are not known but Hp induction of cytokines is
      believed to be involved. However, the profile as well as the involvement of
      cytokines induced by Hp infection is less clear. In the present study, steady
      state levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNFalpha) and
      TGFbeta1 mRNA of human gastric epithelial cell lines Kato III, AGS and NCI-87N in
      response to Hp infection were investigated. The cell cultures were infected with
      Hp for up to 18 h. Total RNA was extracted and analyzed by reverse transcription
      PCR. The three cell lines tested expressed low constitutive levels of mRNA for IL
      8 and TNFalpha. The mRNA levels of IL-8 quickly increased within 2 h in all three
      cells tested and reached a peak at 4 h following infection with Hp. In contrast,
      the levels of TNFalpha after Hp infection increased in only Kato III cells. The
      other cells, AGS and NCI-87N, responded with minimum increases after Hp
      infection. The TGFbeta1 mRNA was constitutively expressed in both AGS and NCI-87N
      cells, but Kato III cells expressed only low levels prior to infection. The Hp
      infection did not increase the levels of TGFbeta1 mRNA as well as TGFbeta1
      secretion in all cells tested. These results indicate that the cytokine response
      to Hp infection differs according to the cells studied and the response may be
      linked somewhat to TGF levels of gastric cells.

PMID- 10967257
TI  - Calprotectin (MRP8/14 protein complex) release during mycobacterial infection in
      vitro and in vivo.
AB  - The calprotectin (MRP8/14) protein complex belongs to the S100 family of Ca2+
      binding proteins and is expressed during myelomonocytic differentiation. MRP8/14
      plasma levels were determined by ELISA in 35 patients with active pulmonary
      tuberculosis (TB) showing mild (n = 12), moderate (n = 11) or severe (n = 12)
      disease, 13 patients with active pulmonary sarcoidosis (SR) and 21 healthy
      controls. TB patients had significantly increased plasma levels of MRP8/14 in
      comparison with SR and controls, which significantly depended on the volume of
      lung tissue involved in the inflammatory process. In TB patients, there was no
      correlation between plasma levels of MRP8/14 and total white blood cell (WBC)
      count, and blood polymorphonuclear neutrophil (PMN) count. In SR patients,
      MRP8/14 plasma levels were twofold higher in comparison with controls, but were
      lower compared with mild TB, and correlated with PMN and WBC counts. Human
      monocytes infected and cultured for 7 days with Mycobacterium bovis bacillus
      Calmette-Guerin showed fivefold higher MRP8/14 levels in supernatants compared
      with unstimulated or purified protein derivative-stimulated cells. Human MRP8/14
      significantly increased Mycobacterium tuberculosis H37Rv growth in liquid medium
      in a dose- and time-dependent manner. These findings suggest that MRP8/14 plays
      an important role in the immunopathogenesis of tuberculosis.

PMID- 10967258
TI  - A PCR-based approach to sequence the Candida tropicalis HSP90 gene.
AB  - The heat shock protein 90 (hsp90) gene sequence is known to be highly conserved
      across the species barrier. A PCR-based method was thus utilised in an attempt to
      sequence the Candida tropicalis hsp90 gene. Primers for PCR were designed from
      conserved regions of the gene, which were identified by comparing the
      Saccharomyces cerevisiae and Candida albicans hsp90 gene sequences. Different
      sets of primers were designed to amplify and obtain overlapping DNA sequences of
      the C tropicalis gene. PCR was carried out on genomic DNA of Candidca tropicalis
      and the PCR products were cloned into suitable vector molecules for sequencing.
      In this way, a 2,070-basepair sequence of the C. tropicalis hsp90 gene was
      obtained. The PCR-based approach proved to be an easier method of obtain the
      sequence of a highly conserved gene, as compared to more conventional methods.

PMID- 10967259
TI  - Staphylococcus aureus alpha-toxin induces apoptosis in endothelial cells.
AB  - The internalization of Staphylococcus aureus by cultured human umbilical vein
      endothelial cells was recently shown to induce apoptosis. We examined the role of
      alpha-toxin, a major pore-forming toxin secreted by S. aureus, in causing
      apoptosis in vitro. Purified alpha-toxin, at sublytic concentrations, induced
      apoptosis in endothelial cell monolayers. Comparisons of two alpha-toxin (hla)
      positive S. aureus strains and their isogenic hla-deficient mutants in the
      invasion assay of endothelial cells demonstrated that the capacity to produce
      alpha-toxin was associated with a greater propensity for apoptosis in endothelial
      cells. These results demonstrate for the first time that expression of alpha
      toxin during endothelial cell invasion by S. aureus enhances apoptosis.

PMID- 10967260
TI  - Modulation of humoral immune response through probiotic intake.
AB  - Thirty healthy volunteers were randomised into three different treatment groups
      and consumed Lactobacillus GG, Lactococcus lactis or placebo (ethyl cellulose)
      for 7 days. On days 1, 3 and 5, an attenuated Salmonella typhi Ty21a oral vaccine
      was given to all subjects to mimic an enteropathogenic infection. All subjects
      responded well to the vaccine, but no significant differences were observed in
      numbers of IgA-, IgG- and IgM-secreting cells among the different groups. There
      was a trend towards a greater increase in specific IgA among the subjects
      receiving the vaccine in combination with Lactobacillus GG. Those receiving L.
      lactis with their vaccine evinced significantly higher CR3 receptor expression on
      neutrophils than those receiving either the placebo or Lactobacillus GG. These
      results indicate that probiotics may influence differently the immune response to
      oral S. typhi vaccine and that the immunomodulatory effect of probiotics is
      strain-dependent.

PMID- 10967261
TI  - Identification and characterization of pseudomonas aeruginosa PA-IIL lectin gene
      and protein compared to PA-IL.
AB  - Using the 33 N-terminal amino acids of the fucose/mannose binding lectin PA-IIL
      of Pseudomonas aeruginosa ATCC 33347 in a tblastn search of P. aeruginos PAOI
      genomic sequence in GenBank revealed a single open reading frame encoding a 114
      amino acid protein (excluding initiator methionine) perfectly matching that amino
      acid sequence. Following its stop codon there is a GC-rich sequence having a
      perfect dyad symmetry promoting formation of a hairpin loop structure,
      potentially enabling rho-independent transcription termination. Upstream of the
      putative ribosomal binding site there are sequences resembling Vibrio fischeri
      luxIbox. consistent with autoinduction of this gene, The predicted PA-IIL
      molecular mass, confirmed by mass spectrometry, is 11,732 Da. Its pI is 3.88. The
      C-terminal domain is particularly hydrophobic, implying possible embedding in the
      cell membrane. PA-IIL is similar to P. aeruginosa PA-IL lectin in some amino
      acids and potential glycosylation sites but lacks cysteine, methionine and
      histidine. Despite their relations in functions and regulation.,their genes are
      widely separated (by about 867.5 kb).

PMID- 10967262
TI  - Role of strain type, AGS cells and fetal calf serum in Helicobacter pylori
      adhesion and invasion assays.
AB  - In a human gastric biopsy specimen, 30% of adhering Helicobacter pylori strain
      AF4 (cagA and VacA positive) was associated with adhesion pedestals. In an AGS
      cell assay, only a few percent of this type I strain was found to be associated
      with adhesion pedestals. Nevertheless, a larger proportion of the type I strain
      was found to invade AGS cells (P < 0.03) and to attach with depressions in the
      AGS cell membrane (P < 0.03) than a type II strain (cagA and VacA negative).
      Incubation of AGS cells and H. pylori without adding fetal calf serum (FCS) to
      the culture medium increased actin accumulations (FITC-phalloidin stained)
      beneath adhering H. pylori, and decreased H. pylori invasion of AGS cells
      significantly (P < 0.01). However, no increase in the number of adhesion
      pedestals was observed by electron microscopy. Proteinase K treatment of FCS
      eliminated the H. pylori invasion promoting effect (P < 0.01). Our results
      suggest differences in the ability of H. pylori to induce adhesion pedestals in
      human gastric epithelial cells and in AGS cells, but a correlation between
      adhesion pedestal formation in vivo and H. pylori invasion in vitro can be
      speculated. In addition, H. pylori invasion into AGS cells was found to be
      mediated by proteins in FCS.

PMID- 10967263
TI  - Measurement of blood clearance time by Limulus G test of Candida-water soluble
      polysaccharide fraction, CAWS, in mice.
AB  - The Limulus G test, responsive to beta-1,3-D-glucan, is a well-established method
      for the detection of invasive fungal infection. We have recently found that
      Candida albicans released a water-soluble polysaccharide fraction (CAWS) into
      synthetic medium (Uchiyama et al., FEMS Immunol. Med. Microbiol. 24 (1999) 411
      420). CAWS was composed of a mannoprotein-beta-glucan complex and activated
      Limulus factor G, and thus would be similar to the Limulus active substance in
      patient's blood. In a preliminary investigation, we have found that CAWS is
      lethal when administered intravenously in a murine system. In this study, we
      examined the toxicity and then the fate of CAWS in mice. The lethal toxicity was
      strain-dependent and strain DBA/2 was the most resistant. The toxicity was, at
      least in part, reduced by salbutamol sulfate and prednisolone treatment in the
      sensitive strains. On intravenous administration, the half clearance time (t1/2)
      was approximately 40 min in mice (DBA/2). On intraperitoneal administration, CAWS
      appeared in the blood with a peak concentration at 1 h. In order to establish a
      treatment plan, it is important to demonstrate the onset and the termination of
      deep-seated mycosis. The Limulus G test is suitable for the above purpose;
      however, it is necessary to fully understand the fate of beta-1,3-D-glucan in
      patients' blood.

PMID- 10967265
TI  - Prevention and treatment of cytomegalovirus disease in heart transplant patients.
AB  - Cytomegalovirus (CMV) remains the most important infection affecting heart
      transplant recipients. Treatment of clinical disease is with a two to three-week
      course of intravenous ganciclovir, which is effective in more than 90% of
      individuals. However, relapsing disease, particularly in those with primary
      infection, is an increasing problem, occasionally with the development of
      ganciclovir-resistant infection. In those instances, foscarnet is needed, despite
      its nephro- and neurotoxicities. Increasingly, in order to prevent relapse, more
      prolonged oral courses of anti-viral therapy are being added to the standard two
      to three-week course of intravenous treatment. In the prevention of CMV disease,
      those at risk of primary disease (donor seropositive, recipient seronegative)
      should receive prophylaxis; for seropositive transplant patients, preemptive
      strategies linked to immunosuppression or viremia monitoring are becoming
      increasingly prevalent. In the future, as new drugs become available, the
      essential question will be whether chronic allograft injury (i.e., accelerated
      coronary artery atherosclerosis) can be prevented with an anti-viral strategy.

PMID- 10967264
TI  - Complement as a mediator of vascular inflammation and activation in allografts.

PMID- 10967266
TI  - Bone mineral density in lung-transplant recipients before and after graft:
      prevention of lumbar spine post-transplantation-accelerated bone loss by
      pamidronate.
AB  - BACKGROUND: Lung-transplant recipients are at risk of osteoporosis. They may have
      low bone mass even before posttransplantation immunosuppressive therapy. We
      studied bone mineral density (BMD) before and after lung transplantation and
      compared the efficacy of antiresorptive therapies to calcium and vitamin D
      supplementation. METHODS: Areal BMD was assessed in 42 patients awaiting lung
      transplantation and measured again after surgery at 6 (n = 29), and at 12 months
      (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV
      every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10
      patients received only calcium and vitamin D supplements. RESULTS: Mean age- and
      gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly
      decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2
      standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic
      (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score.
      Antiresorptive therapy decreased the rate of LS bone loss during the first 6
      months and led to a significant increase of BMD at 1 year, with LS changes of +
      0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002),
      and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients
      experienced clinically evident fractures during antiresorptive therapy, and 3 out
      of 12 in the calcium-vitamin D group. CONCLUSION: A significant proportion of
      patients awaiting lung transplantation was osteoporotic or osteopenic.
      Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT))
      prevented accelerated LS bone loss after graft.

PMID- 10967267
TI  - Active CMV infection before lung transplantation: risk factors and clinical
      implications.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity
      following lung transplantation, but active CMV infection has not been described
      before transplantation. Since 1990, we have screened all lung-transplant
      recipients for CMV infection with viral urine cultures on the day of
      transplantation. We retrospectively reviewed the medical records of all 102 lung
      allograft recipients transplanted between March 1990 and September 1998. Patients
      with positive urine cultures for CMV were compared to culture negative patients
      for age, gender, pretransplant diagnosis, time from diagnosis to transplantation,
      CMV serostatus, use of pretransplant immunosuppression, T-lymphocyte subsets, and
      presence of fever. Posttransplant outcomes assessed were duration of intubation
      and hospitalization, acute rejection, frequency of CMV disease, duration of
      Nashville rabbit antithymocyte serum or globulin (N-RATS/G) and ganciclovir, and
      survival. Five (5%) of 102 patients had positive urine cultures for CMV; none had
      symptoms of CMV infection. All 5 had idiopathic pulmonary fibrosis (IPF) (5/5 vs
      27/97; p = 0.002). The age, gender, and CMV serostatus of these patients did not
      differ from the 97 patients in the culture negative group. Four (80%) of the 5
      patients with positive cultures were receiving treatment with azathioprine or
      cyclophosphamide vs only 18 (19%) of the 97 patients with negative cultures (p =
      0.007), and all 5 (100%) were receiving steroids compared to 50 (52%) of 97
      patients with negative cultures (p = 0.06). Culture-positive IPF patients, when
      compared with the 27 culture-negative IPF patients, did not differ in any
      demographic variable or in the use of immunosuppression, but culture-positive
      patients were more likely to have a CD4/CD8 T-cell subset ratio <1.0 (p = 0.02).
      Following transplantation, 3 (60%) of 5 IPF patients with positive CMV cultures
      developed CMV disease compared to 3 (11%) of 27 IPF patients with negative
      cultures (p = 0.03). Patients with positive cultures also received more days of
      parenteral antiviral therapy (mean 44 +/- 11 days vs 16 +/- 10 days; p < 0.001).
      Utilizing pretransplant screening, we have discovered that 16% of patients with
      IPF had active CMV infection, which was associated with both alterations in their
      T-cell subsets and a greater risk for CMV disease after transplantation. This
      occurrence of occult CMV infection in patients with IPF has not been previously
      recognized, and has important implications.

PMID- 10967268
TI  - Outcome while awaiting heart transplantation in children: a comparison of
      congenital heart disease and cardiomyopathy.
AB  - BACKGROUND: Outcomes for children who undergo heart transplantation differ for
      children with congenital heart disease as compared to those with structurally
      normal hearts. Similar data have not been reported for these groups of patients
      for the morbidity and mortality associated with waiting for a donor. We report
      these data. METHODS: A retrospective review was performed for all pediatric
      patients who were listed for heart transplantation at Stanford from 1977 to 1996,
      comparing mortality and major morbidity for patients with congenital heart
      disease and those with cardiomyopathy and structurally normal hearts. RESULTS:
      There were 96 patients who met study criteria, of whom 67 were successfully
      transplanted. The median waiting time was 23 days. Survival at 30 days was 93%
      and at 90 days was 81%, with no difference between groups. Major complications
      were identified in 38% of patients with structurally normal hearts, vs 9% of
      patients with congenital heart disease (p < 0.001). CONCLUSIONS: Overall
      mortality is similar for patients with congenital heart disease and those with
      structurally normal hearts while listed for heart transplantation, but patients
      with congenital heart disease have fewer episodes of major morbidity during this
      time.

PMID- 10967269
TI  - Non-invasive assessment of rejection in pediatric transplant patients: serologic
      and echocardiographic prediction of biopsy-proven myocardial rejection.
AB  - BACKGROUND: Cardiac allograft rejection is a multifocal immune process that is
      currently assessed using biopsy-guided histologic classification systems
      (International Society for Heart and Lung Transplantation). Cardiac troponin T
      and I are established serologic markers of global myocyte damage. The use of load
      independent measures of contractility have also been shown to accurately assess
      the presence of ventricular dysfunction. Little is known about their utility in
      accurately predicting rejection in the pediatric age group. We undertook the
      present study to compare rejection grade with echocardiographic and serologic
      estimates of transplant rejection-related myocardial damage. METHODS: We compared
      histologic rejection grades (0 to 4) with patient characteristics,
      echocardiographic measurements, catheterization measurements, and biochemical
      markers for 86 evaluations in 37 transplant recipients at Children's Hospital.
      RESULTS: In univariate analyses, biopsy scores correlated (p < 0.05) inversely
      with left ventricular systolic function (shortening fraction) and contractility
      (stress velocity index, SVI), and directly with mitral E-wave amplitude. In
      multivariate analyses, lower contractility and higher mitral E-wave amplitude
      remained significantly (p < or = 0.01) associated with rejection (SVI, p = 0.002,
      odds ratio = 0.393; E wave, p = 0.0002, odds ratio = 228). Most rejection
      episodes were associated with elevation of biochemical markers of myocardial
      injury. Although troponin I was weakly associated with differences between
      rejection grades (p = 0.034), troponin T, creatine kinase-MB fraction, and C
      reactive protein did not differ with biopsy-rejection scores. Serum markers had a
      poor predictive capacity for biopsy-detected rejection. Troponin T and I did
      correlate with increased left ventricular wall thickness and mass. CONCLUSION:
      Progressively depressed left ventricular contractility and diastolic function are
      found with worsening pediatric heart transplant rejection-biopsy score; however,
      sensitive and specific serum markers do not correspond to the degree of active
      myocardial injury. The use of echocardiographic measures of contractility is
      associated with a specificity of 91.8% but low sensitivity of 66.7%. Overall we
      found poor concordance between serum markers and grade of rejection. It is
      unclear whether myocardial injury as assessed by serum markers, echocardiography,
      or histologic scoring is more important for assessment of acute rejection or long
      term outcome, but it does not appear that serum and tissue markers of rejection
      can be used interchangeably.

PMID- 10967270
TI  - Genetic variations of the apolipoprotein E gene determine the plasma triglyceride
      levels after heart transplantation.
AB  - OBJECTIVES: To study whether the presence of the polymorphism in the
      apolipoprotein E (apo E) gene influences the lipid profile in heart-transplant
      recipients. METHODS: A cohort of 103 recipients of heart transplant (93 men and
      10 women, with a mean age of 47 +/- 13 years) under triple immunosuppressive
      therapy were submitted to a genetic study of the apo E gene region.
      Anthropometric and analytical data, including lipid profile and arterial blood
      pressure were collected prior to transplantation and 3, 6, 12, and 24 months
      after it. RESULTS: 65 subjects present the genotype E3E3, 27 the genotype E3E4, 6
      the genotype E2E3, and 5 the genotype E2E4. Carriers of the E2 allele (that is,
      genotypes E3E2 and E4E2) had higher total plasma triglyceride (TG) levels after 3
      months (3.47 +/- 1.88 mmol/liter p < 0.001) and after 1 year of transplantation
      (3.13 +/- 1.77 mmol/liter p < 0.05) than the other genotypes. There were no
      differences in the plasma levels of total cholesterol (TC), LDL-cholesterol (LDL
      C), and HDL-cholesterol (HDL-C). Multiple regression analysis revealed that the
      apoprotein E gene polymorphism determines 5% (p = 0.0425) and age 8.7% (p <
      0.009) of the variants in TG levels. CONCLUSIONS: The presence of the E2 allele
      in heart-transplant recipients produces a greater rise in total TG plasma levels
      than the other genotypes.

PMID- 10967271
TI  - A prospective study of a quantitative PCR ELISA assay for the diagnosis of CMV
      pneumonia in lung and heart-transplant recipients.
AB  - BACKGROUND: Qualitative polymerase chain reaction (PCR) for the identification of
      cytomegalovirus (CMV) infection has a low predictive value for the identification
      of CMV pneumonia. This study prospectively evaluated the application of a
      quantitative PCR Enzyme-Linked Immuno-Sorbent Assay (ELISA) assay in 9 lung- and
      18 heart-transplant recipients who did not receive ganciclovir prophylaxis.
      METHODS: DNA was collected from peripheral blood polymorphonuclear leucocytes
      (PMNL) posttransplantation. Oligonucleotide primers for the glycoprotein B gene
      (149 bp) were used in a PCR ELISA assay using an internal standard for
      quantitation. CMV disease was defined as histological evidence of end organ
      damage. RESULTS: The median level CMV genome equivalents in patients with CMV
      disease was 2665/2 x 10(5) PMNL (range 1,200 to 61,606) compared to 100 x 10(5)
      PMNL (range 20 to 855) with infection but no CMV disease (p = 0.036). All
      patients with CMV disease had genome equivalents levels of >1200/2 x 10(5) PMNL.
      A cut-off level of 1,200 PMNL had a positive predictive value for CMV disease of
      100% and a negative predictive value of 100%. The first detection of levels of
      CMV genome equivalents above a level of 1200/2 x 10(5) PMNL was at a median of 58
      days (range 47 to 147) posttransplant. CONCLUSIONS: Quantitative PCR assays for
      the diagnosis of CMV infection may predict patients at risk of CMV disease and
      thereby direct preemptive treatment to high-risk patients.

PMID- 10967272
TI  - Outcomes in patients who are hepatitis B surface antigen-positive before
      transplantation: an analysis and study using the joint ISHLT/UNOS thoracic
      registry.
AB  - BACKGROUND: Hepatitis B surface antigenemia (HBsAg) has been considered at least
      a relative contraindication for heart transplantation, yet patients have
      undergone liver transplantation for hepatitis B-induced chronic liver disease,
      albeit with poorer results than for other liver diseases. The impact of
      asymptomatic hepatitis B infection on heart transplant outcome is not known.
      METHODS: To examine this question, we queried the Joint International Society for
      Heart and Lung Transplantation/United Network of Organ Sharing Thoracic Registry
      for all patients undergoing heart transplantation who had been identified as
      positive for HBsAg before transplantation. We then sent a 4-question data
      instrument to the centers responsible for the identified patients. Seventy-eight
      patients were identified. Of the 78 data forms sent, 53 forms were returned with
      the requested data. Of the 53 data forms returned, the centers incorrectly
      identified 23 patients as positive for HBsAg, resulting in 30 patients who were
      confirmed as HBsAg positive and who served as the final cohort for this analysis.
      RESULTS: The cohort included 24 males and 6 females, with a mean age of 46 +/- 16
      years (range 0 to 68 years). Eleven patients had coronary artery disease, 14 had
      dilated cardiomyopathy, and 5 patients had a variety of other cardiac diseases.
      Of those tested at most recent follow-up, 20 of 25 patients continued to be
      positive for HBsAg, whereas 7 of 21 patients studied had converted and were
      hepatitis B serum antibody-positive. Approximately 37% of the patients had
      evidence of active hepatic inflammation or cirrhosis. We found a statistically
      significant correlation between positivity for hepatitis C antibodies and
      clinical liver disease (p = 0.0105). No difference in survival could be
      demonstrated between the study cohort and a reference heart transplant cohort,
      yet 5 of the 9 deaths were considered to be related to hepatitis B. CONCLUSIONS:
      These data demonstrate that clinical liver disease is common post-transplantation
      in HBsAg+ patients who presumably have no overt liver disease at the time of
      transplantation. Despite the inability to show a survival difference in this
      cohort, the fact that the majority of deaths were related to hepatitis B should
      suggest caution in accepting HBsAg+ patients for cardiac transplantation.

PMID- 10967273
TI  - Myocardial neutrophil sequestration during reperfusion of the transplanted rabbit
      heart.
AB  - BACKGROUND: Neutrophils are major participants in myocardial reperfusion injury,
      but the relationship between ischemic time and the extent of the neutrophil
      sequestration in heart transplantation has not yet been systematically studied.
      This study was designed to determine whether increased ischemic time would cause
      greater neutrophil sequestration during reperfusion of the globally ischemic
      heart. METHODS: Rabbit hearts were arrested with cardioplegia, explanted, and
      subjected to either 1 or 4 hours of global ischemia at 4 degrees C before being
      heterotopically transplanted into a recipient rabbit's abdomen for reperfusion.
      Each heart was reperfused for either 4, 8, or 12 hours. Between 3 and 7 hearts
      were studied (average = 5.8) for each combination of ischemic and reperfusion
      time (total = 35). A myeloperoxidase (MPO) assay was used to qualify neutrophil
      content. RESULTS: MPO activity (U/g wet weight) was not significantly different
      at 4, 8, and 12 hours of reperfusion (0.33 +/- 0.05, 0.20 +/- 0.04, 0.26 +/-
      0.04: p = 0.13), but was significantly increased at 4 hours compared to 1 hour
      ischemia (0.34 +/- 0.04 vs 0.19 +/- 0.03: p = 0. 006). Interaction between
      ischemic and reperfusion times was not significant (p = 0.12). MPO activity was
      below the measurable threshold in 5 freshly excised control hearts. CONCLUSIONS:
      These results suggest that acute reperfusion injury will be more severe in the
      hearts subjected to 4 hours ischemia and indicate the need to consider neutrophil
      mediated reperfusion injury when addressing cardioprotective interventions for
      cardiac preservation and reperfusion after transplantation. Neutrophil-mediated
      reperfusion injury of the rabbit myocardium after heterotopical transplantation
      is more severe in hearts subjected to 4 hours of ischemia vs 1 hour of ischemia
      prior to transplantation.

PMID- 10967274
TI  - Microperfusion techniques for long-term hypothermic preservation.
AB  - BACKGROUND: The aim of this study was to compare several methods of hypothermic
      heart preservation. METHODS: We preserved isolated pig hearts for 24 hours in
      cold cardioplegia (4 degrees C), using either continuous microperfusion (Group I)
      or simple storage (Group II), and with a new preservative solution (NPS, groups
      IA and IIA) vs St. Thomas' solution (groups IB and IIB). The main characteristics
      of the NPS include (1) prevention of cell swelling with polyethelene glycol
      (PEG), (2) low calcium and magnesium, and (3) presence of metabolic substrates,
      such as glucose, insulin, pyruvate, aspartate, alanyl-glutamine, and membrane
      stabilization compounds such as ethanol and chlorpromazine. RESULTS: The 4 above
      groups were compared with hearts harvested and immediately reperfused (control
      group). During preservation, only Group IB showed significant edema (40% +/- 8.4%
      water gain). Adenylate charge was 25% to 50% higher in microperfused Groups IA
      and IB (0.678 +/- 0.049 and 0.795 +/- 0.071, respectively) as compared with
      simple-storage groups IIA and IIB (0.605 +/- 0.048 and 0.524 +/- 0.160,
      respectively). Ultrastructural analysis showed that tissue injury occurred mainly
      in Group IIB (altered mitochondria, chromatin clumping). Functional data showed
      better recovery of NPS groups as compared with St. Thomas groups: coronary flow
      was identical in Group IB and control (57.8 +/- 22 and 56.6 +/- 14 ml/min/100 g,
      respectively), and in IA > IB (p < 0.001) and IIA > IIB (p < 0.01); the rate
      pressure products were higher in NPS groups compared with St. Thomas groups (IA >
      IB, p < 0.01); IIA > IIB, p < 0.05). CONCLUSIONS: The microperfusion method
      associated with the NPS provides excellent protection in long-term hypothermic
      heart preservation.

PMID- 10967275
TI  - Long-term outcome of cardiac allograft vasculopathy treated by transmyocardial
      laser revascularization: early rewards, late losses.
AB  - Transmyocardial laser revascularization (TLR) was initially touted as a promising
      therapeutic alternative for tackling the growing problem of cardiac allograft
      vasculopathy in late heart transplant survivors. We first described 4- and 8-week
      observations of application of this surgical technique, in which we professed
      enthusiasm for TLR in providing symptomatic relief and in reducing ischemic
      burden. In this report, we present the long-term (24-month) impact of TLR on
      clinical outcome, channel patency, and recrudescence of ischemic burden. In the
      long term, surgical TLR provides neither consistent symptomatic improvement nor
      an ameliorative effect on the natural history of cardiac allograft vasculopathy.

PMID- 10967277
TI  - Management strategies for heparin-induced thrombocytopenia in heart-transplant
      candidates: case report and review of the literature.
AB  - Management of anticoagulation in patients with heparin-induced thrombocytopenia
      (HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac
      transplantation, represents a difficult clinical problem and no clear management
      strategy exists. The cases of 2 patients with HIT who underwent cardiac
      transplantation using differing anticoagulation strategies are presented with a
      discussion of potential advantages and pitfalls of each approach used.

PMID- 10967276
TI  - Early post-transplant lymphoproliferative disease following heart transplantation
      in the absence of lymphocytolytic induction therapy.
AB  - We report a case of post-transplant lymphoproliferative disease presenting as a
      disseminated polymorphous B-cell lymphoma involving the cardiac allograft 3
      months following transplantation in a recipient who did not receive anti
      lymphocyte induction immunosuppression. In situ hybridization for the lytic
      Epstein-Barr virus marker NOT I was positive within a lymphocytic infiltrate on
      endomyocardial biopsy. Our case is the third of early post-transplant
      lymphoproliferative disease (within 6 months of transplantation) involving the
      heart allograft in the absence of anti-lymphocyte induction immunosuppression.
      Post-transplant lymphoproliferative disease of the heart allograft should be
      considered in the presence of an atypical cardiac lymphocytic infiltrate, with
      possible differentiation from allograft rejection using in situ hybridization for
      Epstein-Barr virus.

PMID- 10967278
TI  - Comparison of the efficacy and cost-effectiveness of pre-emptive therapy as
      directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant
      recipients.

PMID- 10967279
TI  - Human polyomavirus JC variants in Papua New Guinea and Guam reflect ancient
      population settlement and viral evolution.
AB  - The peopling of the Pacific was a complex sequence of events that is best
      reconstructed by reconciling insights from various disciplines. Here we analyze
      the human polyomavirus JC (JCV) in Highlanders of Papua New Guinea (PNG), in
      Austronesian-speaking Tolai people on the island of New Britain, and in nearby
      non-Austronesian-speaking Baining people. We also characterize JCV from the
      Chamorro of Guam, a Micronesian population. All JCV strains from PNG and Guam
      fall within the broad Asian group previously defined in the VP1 gene as Type 2 or
      Type 7, but the PNG strains were distinct from both genotypes. Among the Chamorro
      JCV samples, 8 strains (Guam-1) were like the Type 7 strains found in Southeast
      Asia, while nine strains (Guam-2) were distinct from both the mainland strains
      and most PNG strains. We identified three JCV variants within Papua New Guinea
      (PNG-1, PNG-2 and PNG-3), but none of the Southeast Asian (Type 7) strains. PNG-1
      strains were present in all three populations (Highlanders and the Baining and
      Tolai of New Britain), but PNG-2 strains were restricted to the Highlanders.
      Their relative lack of DNA sequence variation suggests that they arose
      comparatively recently. The single PNG-3 strain, identified in an Austronesian
      speaking Tolai individual, was closely related to the Chamorro variants (Guam-2),
      consistent with a common Austronesian ancestor. In PNG-2 variants a complex
      regulatory region mutation inserts a duplication into a nearby deletion, a change
      reminiscent of those seen in the brains of progressive multifocal
      leukoencephalopathy patients. This is the first instance of a complex JCV
      rearrangement circulating in a human population.

PMID- 10967280
TI  - Experimental histoplasmosis in mice treated with anti-murine interferon-gamma
      antibody and in interferon-gamma gene knockout mice.
AB  - Histoplasma capsulatum is an important fungal pathogen in immunocompromised
      hosts, including AIDS patients. Experimental evidence suggests interferon-gamma
      (IFN) plays a role in host defense against H. capsulatum. In these studies we
      sought to demonstrate the importance of IFN in innate resistance to systemic
      histoplasmosis. The possible exacerbation of infection in BALB/c mice was
      assessed by administering 200 microg of hamster anti-IFN antibody prior to
      infection with H. capsulatum (2 x 10(6) yeasts, i.v.) and by comparing the
      severity of infection between BALB/c IFN gene knockout mice (GKO) and congenic
      control animals. In two separate studies, we found that anti-IFN treatment caused
      a dramatic loss of resistance to lethal infection and resulted in earlier
      mortality of IFN-depleted animals compared with normal IgG or no treatment
      (P<0.001). GKO mice were significantly (P<0.001) more susceptible to lethal
      infection than were control animals, and histological studies corroborated this.
      These studies clearly demonstrate that IFN is a vital part of the host's innate
      resistance to systemic infection with H. capsulatum and provide an additional
      rationale for studying IFN as an immunomodulatory therapeutic for the treatment
      of this disease.

PMID- 10967281
TI  - Impaired immunogenicity of immunostimulating complexes (iscoms) by administration
      in slow-release formulations.
AB  - This study was performed to explore the possible benefits of formulations and
      administration regimens that allow a protracted release of iscoms from the
      injection site. Three forms of slow release of immunostimulating complexes
      (iscoms) were therefore tested; encapsulation in sodium alginate gel,
      emulsification in Freund's incomplete adjuvant (FIA) or pulsed-release mimicked
      by weekly administrations. The administration of iscoms in a depot (alginate or
      FIA) or in pulses resulted in an antibody response of similar magnitude to that
      of a traditional two-dose scheme. The character of the immune response was on the
      other hand affected, i.e. the proportion of specific IgG2a and the IFN-gamma
      production was decreased by a protracted or repeated release of iscoms, either by
      a depot or by weekly administrations.

PMID- 10967282
TI  - Regulation of cell cycle and apoptosis by human immunodeficiency virus type 1
      Vpr.
AB  - Biological effects of HIV-1 Vpr on CD4(+) cells were studied by an infection
      system. High-titered HIV-1 stocks pseudotyped with vesicular stomatitis virus G
      protein were prepared and used to inoculate into CD4(+ )T cells at high
      multiplicity of infection. Both cell- and virion-associated Vpr were demonstrated
      to arrest the cell cycle at the G2/M phase, and to induce cell apoptosis. Of
      note, morphologically apoptotic cells were shown to be arrested at the G2/M
      stage. No appreciable effect of Vpr on the anti-Fas antibody-mediated apoptosis
      was observed in this system.

PMID- 10967283
TI  - Evolution of the CD8 T-cell repertoire during infections.
AB  - CD8 T cells exist in a dynamic network whose repertoire remains static in the
      absence of infection but changes in the presence of foreign antigens. Individuals
      each have unique T-cell repertoires that continually evolve in the presence of
      antigen and of cross-reactive heterologous antigens, and homeostatic forces drive
      deletions in T-cell memory pools to accommodate the entry of new memory cells
      into a finite immune system.

PMID- 10967284
TI  - Dengue viral infections; pathogenesis and epidemiology.
AB  - Dengue viral infections affect up to 100 million individuals per year. Dengue
      haemorrhagic fever is a clinical form of disease characterised by intravascular
      fluid loss. There has been a marked increase in the incidence of this form of the
      disease over the last few decades, associated with significant mortality,
      particularly in the paediatric population. A number of theories relating to the
      pathogenesis of dengue haemorrhagic fever exist that have evolved from the
      analysis of the epidemiology of this disease. Virological and immunopathological
      factors are both important but the exact mechanisms for the disease are unknown.

PMID- 10967285
TI  - Establishment of Pseudomonas aeruginosa infection: lessons from a versatile
      opportunist.
AB  - Pseudomonas aeruginosa is an ubiquitous pathogen capable of infecting virtually
      all tissues. A large variety of virulence factors contribute to its importance in
      burn wounds, lung infection and eye infection. Prominent factors include pili,
      flagella, lipopolysaccharide, proteases, quorum sensing, exotoxin A and
      exoenzymes secreted by the type III secretion system.

PMID- 10967287
TI  - The immune response against Helicobacter pylori--a direct linkage to the
      development of gastroduodenal disease.
AB  - Helicobacter pylori infects about half of the world's population. H. pylori
      elicits marked immune responses, but the infection is commonly life-long. Some
      infected individuals remain asymptomatic, while others develop significant
      gastroduodenal disease. We review the underlying host immune response to H.
      pylori which programs for persistence and evolution of gastroduodenal disease.

PMID- 10967286
TI  - Secretion of virulence determinants by the general secretory pathway in gram
      negative pathogens: an evolving story.
AB  - Secretion of proteins by the general secretory pathway (GSP) is a two-step
      process requiring the Sec translocase in the inner membrane and a separate
      substrate-specific secretion apparatus for translocation across the outer
      membrane. Gram-negative bacteria with pathogenic potential use the GSP to deliver
      virulence factors into the extracellular environment for interaction with the
      host. Well-studied examples of virulence determinants using the GSP for secretion
      include extracellular toxins, pili, curli, autotransporters, and crystaline S
      layers. This article reviews our current understanding of the GSP and discusses
      examples of terminal branches of the GSP which are utilized by factors implicated
      in bacterial virulence.

PMID- 10967288
TI  - Response of the ruminant respiratory tract to Mannheimia (Pasteurella)
      haemolytica.
AB  - Pneumonia is a leading cause of loss to the sheep and cattle industry throughout
      the world. Mannheimia (Pasteurella) haemolytica is one of the most important
      respiratory pathogens of domestic ruminants and causes serious outbreaks of acute
      pneumonia in neonatal, weaned and growing lambs, calves, and goats. M.
      haemolytica is also an important cause of pneumonia in adult animals.
      Transportation, viral infections with agents such as infectious bovine
      rhinotracheitis virus, parainfluenza-3 virus or bovine respiratory syncytial
      virus, overcrowding, housing of neonates and weaned animals together and other
      stressful conditions predispose animals to M. haemolytica infection [1, 2]. This
      review assimilates some of the findings key to cellular and molecular responses
      of the lung from a pathologist's perspective. It includes some of what is known
      and underscores areas that are not fully understood.

PMID- 10967289
TI  - DNA polymorphism in the genus Brucella.
AB  - The genus Brucella has been described as consisting of six species, three of them
      including several biovars, which display a high degree of DNA homology by DNA-DNA
      hybridization. However, DNA polymorphism able to differentiate the six Brucella
      species and some of their biovars has been shown to exist. This work reviews the
      DNA variability in the genus Brucella and discusses the relationships between its
      members according to this genetic variability and a proposal for their evolution
      based on genetic diversity of the omp2 locus.

PMID- 10967290
TI  - Respiratory fungal allergy.
AB  - Fungal allergy including allergic rhinitis, conjunctivitis, bronchial asthma, and
      allergic bronchopulmonary mycoses results from exposure to spores. In this review
      we have dealt with the common allergenic fungi and allergens, immunopathogenesis,
      diagnostic assays, and the possible control of allergy in the future based on
      epitope-specific immunotherapy and vaccination.

PMID- 10967291
TI  - Physiological significance of apoptosis in animal virus infection.
AB  - In contrast to insect viruses, animal viruses can produce considerable amounts of
      progeny virus in cells undergoing apoptosis. Nevertheless, viruses in general
      have acquired the ability to escape apoptosis of infected cells. These facts
      indicate that the role of apoptosis in virus infection is different in insect
      virus and animal virus, although both viruses need to avoid apoptosis of the
      infected cells for a viral life cycle in nature. In animal virus infection, the
      primary role of apoptosis is considered not to be a premature lysis of the
      infected cells (and the following abortion of virus multiplication) but to allow
      the dying cells to be phagocytosed by macrophages. This phagocytosis is able to
      prevent dysregulated inflammatory reactions at the site of virus infection and to
      initiate a specific immune response against the infected virus.

PMID- 10967292
TI  - Molecular studies of the intestinal mucosal barrier physiopathology using
      cocultures of epithelial and immune cells: a technical update.
AB  - Peyer's patch lymphocytes cocultured with Caco-2 cells trigger the phenotypic
      conversion of enterocytes into cells that express morphological and functional M
      cell properties. We report a technical update for setting up this model, which
      will enable the study of M-cell biology, the identification by biochemical
      approaches of molecules involved in the interaction of microorganisms with M
      cells, and the development of vectors that would efficiently target the mucosal
      immune system.

PMID- 10967293
TI  - Expression, activity and distribution of Na,K-ATPase subunits during in vitro
      neuronal induction.
AB  - The expression pattern of the alpha and beta isoforms and the gamma subunit of
      the Na,K-ATPase was investigated during in vitro induction of pluripotent murine
      embryonic stem (ES) cells into neuronal cells. alpha1 protein was expressed in
      undifferentiated ES (UES) cells and throughout all stages studied. In contrast,
      alpha3 protein was prominent only when neuronal cells have reached full
      differentiation. In this model, neuron-depleted cultures did not express the
      alpha3 isoform, indicating its specificity for mature neuronal cells. UES
      possessed Na,K-ATPase activity consistent with a single isoform (alpha1), whereas
      in fully mature neuronal cells a ouabain-sensitive isoform (alpha3) accounted for
      27+/-4% of the activity, and a ouabain-resistant isoform (alpha1) 66+/-3%.
      Immunocytochemistry of mature neuronal cells for alpha1 and alpha3 proteins
      showed a similar distribution, including cell soma and processes, without
      evidence of polarization. beta1 protein was expressed in uninduced ES, embryonic
      bodies (EB) and neuronal cells. While proteins of the beta2 and beta3 isoforms
      were not detected by immunoblots (except for beta2 in UES), their mRNAs were
      detected in UES and EB (beta2 and beta3), and in immature and fully
      differentiated neuronal cells (beta3). Message for the beta2 isoform, however,
      was not present in neuronal cells. gamma subunit mRNA and protein were
      undetectable at any stage. These results provide further characterization of
      neuron-like cells obtained by induction of ES cells in vitro, and establish a
      model for the expression of isoforms of the Na,K-ATPase during neuronal
      differentiation. The relation to other aspects of neuronal cell development and
      relevance to a specialised function for the alpha3 subunit in neurons are
      discussed.

PMID- 10967294
TI  - Sleep rebound in animals deprived of paradoxical sleep by the modified multiple
      platform method.
AB  - The objective of the present study was to assess the sleep rebound of animals
      exposed to the modified multiple platform method (MMPM), in which cage-mate rats
      were placed onto narrow platforms (NP=6.5 cm in diameter), onto wide platforms
      (WP=14 cm in diameter) or onto a grid (GR). The last two groups were included as
      environmental controls for the deprivation method. Animals were implanted with
      bipolar electrodes in the cortex, hippocampus and neck muscle. Baseline sleep was
      recorded for 6 h, after which the animals were placed in one of the above
      mentioned settings for 90 h and their sleep was again recorded. Comparison
      between baseline and post-GR recordings revealed no sleep differences in these
      animals. Placement of animals onto WP resulted in augmented sleep time (16%),
      time spent in PS (+99%), duration of PS episodes (+77%), sleep efficiency (+16%),
      and in reduced latency to PS (-84.8%). Finally, NP animals exhibited a dramatic
      increase in sleep time (+34.3%), time spent in PS (+184.7%), duration of PS
      episodes (+106%), and in sleep efficiency (+34.4%). Moreover, sleep latency (
      52.2%) and time spent in SWS (-12.2%) were reduced. Based on the results of sleep
      rebound, the data indicated that placement of animals onto narrow platforms in
      the MMPM was an effective PS deprivation method and the grid should be considered
      as an adequate environmental control.

PMID- 10967295
TI  - Discharge modulation of rat dorsal raphe neurons during sleep and waking: effects
      of preoptic/basal forebrain warming.
AB  - In cats, putative serotonergic neurons (PSNs) recorded from the dorsal raphe
      nucleus (DRN) across the sleep-wake cycle exhibit the so-called rapid eye
      movement sleep-off (REM-off) discharge pattern. Since, the sleep-wake discharge
      patterns of DRN neurons in behaving rats is poorly known, the present study
      examined this neuronal populations. The PSNs recorded in this study exhibited:
      (1) progressive decrease in discharge rate from waking to NREM to REM sleep; (2)
      long action potential duration, and (3) reduction of discharge rate after
      systemic administration of a selective 5-HT(1A) agonist, (+/-)-8-hydroxy-2-(di-n
      propylamino) tetralin hydrobromide (8-OH-DPAT). Evidence supports the hypothesis
      that NREM sleep is modulated by thermoregulatory mechanisms localized in the
      preoptic area and adjacent basal forebrain (POA/BF). We previously reported that
      POA/BF warming suppresses the discharge of wake-promoting neurons in the
      posterior hypothalamus and the basal forebrain. Since the DRN is one component of
      the brainstem arousal system and receives projections from POA/BF, we examined
      the effects of local POA/BF warming by 1.5-2.0 degrees C during waking on the
      discharge of DRN neurons. POA/BF warming reduced the discharge in 14 of 19 PSNs
      and in 12 of 17 other wake-related neurons in the DRN. DRN neuronal discharge
      reduction occurred without accompanying EEG frequency or behavioral changes.
      These results suggest that PSNs recorded in DRN in unrestrained and
      unanesthetized rats exhibit a "wake-active REM-off" discharge pattern and further
      support the hypothesis that the POA/BF warm-sensitive hypnogenic system induces
      sleep by a coordinated inhibition of multiple arousal systems including that
      modulated by the DRN.

PMID- 10967296
TI  - An evaluation of the role of 5-HT(2) receptor antagonism during subchronic
      antipsychotic drug administration in rats.
AB  - A widely postulated mechanism of action for the atypical profile of many novel
      antipsychotic drugs (APDs) is their relatively high affinity for 5-HT(2)
      receptors. The present study investigated motor function and striatal dopamine
      (DA) efflux and metabolism in rats given 21 daily injections of drugs that
      differed in 5-HT(2) affinity. These drugs included: risperidone (high 5
      HT(2A/2C)/high D(2)), clozapine (high 5-HT(2A/2C)/low D(2)), haloperidol (low 5
      HT(2A/2C)/high D(2)), haloperidol+ritanserin (selective 5-HT(2A/2C)), or vehicle.
      Rats injected with haloperidol (0.5 mg/kg) or haloperidol+ritanserin (0.5 mg/kg
      and 1.0 mg/kg, respectively) showed extreme catalepsy on day 1, but significantly
      decreased catalepsy when tested again on days 7 and 21. Acute or subchronic
      risperidone (0.05 or 0.5 mg/kg), clozapine (20 mg/kg), or vehicle did not induce
      significant catalepsy. Microdialysis performed 24 h after the last injection
      demonstrated that rats treated with risperidone, clozapine, or vehicle showed
      similar increases in DA efflux and metabolism following an acute injection of a
      selective DA D(2/3) antagonist (raclopride, 0.5 mg/kg). DA efflux showed an
      attenuated response to raclopride in the haloperidol alone group; this effect was
      less apparent in the haloperidol+ritanserin group. However, both of these groups
      showed a similar tolerance effect to the raclopride-induced increase in DA
      metabolites. These results suggest that the profile seen after subchronic
      risperidone more closely resembles clozapine than haloperidol. While ritanserin
      reduced the tolerance-like effects of haloperidol on striatal DA efflux, the
      overall results demonstrate that potent 5-HT(2) blockade alone may not entirely
      account for the distinctive profile of novel APDs.

PMID- 10967297
TI  - Enhanced acquisition of cocaine self-administration in adult rats with neonatal
      isolation stress experience.
AB  - That stress enhances the behavioral effects of cocaine is well-documented in
      adult rats, but whether early life stress endures into adulthood to affect
      responsivity to cocaine is less clear. We now report that neonatal isolation
      stress (1 h per day isolation on postnatal days 2-9) enhances acquisition of
      cocaine self-administration in adult rats. This effect was specific to cocaine
      and not due to learning or performance differences. Neither acquisition of
      operant responding for food nor locomotor activity differed between groups. These
      results have important implications for the role of early childhood stress in
      vulnerability to cocaine addiction.

PMID- 10967298
TI  - Increased cerebrospinal fluid glutamate and taurine concentrations are associated
      with traumatic brain edema formation in rats.
AB  - Glutamate-mediated excitotoxicity results in cell swelling and contributes to
      brain edema formation. Since increased extracellular taurine reflects glutamate
      induced cell swelling in vitro, elevated CSF taurine could therefore unmask
      glutamate-mediated cytotoxic edema formation under in vivo conditions. For this,
      the temporal profile of brain edema and changes in cisternal CSF glutamate and
      taurine levels were determined in 28 rats following focal traumatic brain injury.
      Compared to six non-traumatized rats, CSF glutamate (4. 8+/-0.3 vs. 10+/-0.9
      microM) and taurine levels (12+/-1.3 vs. 41+/-3 microM) were significantly
      increased at 8 h after trauma (P<0.001). Over time, CSF glutamate and taurine
      were significantly increased by 24 (glutamate: 38+/-4.4 microM) and 48 h
      (taurine: 51+/-4 microM), respectively. While CSF glutamate closely reflected
      changes in hemispheric water content, alterations in CSF taurine occurred
      diametrically to those seen for glutamate. Under the present study design,
      increased CSF taurine could reflect glutamate-induced cell swelling. In addition,
      neuronal release of taurine with its inhibitory and antiexcitotoxic functions
      could explain the observed diametric changes in CSF glutamate, CSF taurine, and
      hemispheric water content. Therefore, increasing taurine could be a therapeutic
      approach in attenuating post-traumatic glutamate-mediated cell damage.

PMID- 10967299
TI  - Expression of estrogen receptor-alpha and c-Fos in adrenergic neurons of the
      female rat during the steroid-induced LH surge.
AB  - Epinephrine is an important neurotransmitter that is synthesized in relatively
      few neurons of the medullary regions C1-C3. Epinephrine is involved, among others
      in the control of most neuroendocrine systems, such as corticotropin releasing
      hormone-, gonadotropin releasing hormone- and oxytocin/vasopressin-containing
      neurons as part of complex feedback loop systems that often include interactions
      with the gonadal or adrenal steroid hormones. In order to determine if the
      interactions between gonadal steroid hormones with the adrenergic neurons are
      direct or involve steroid-receptive interneurons that in turn innervate the
      adrenergic neurons, dual immunohistochemistry was applied to identify if estrogen
      receptor-alpha (ERalpha) protein was expressed by adrenergic, phenylethanolamine
      N-methyl transferase (PNMT)-positive neurons and if estradiol can activate these
      neurons as determined by the transient expression of the transcription factor c
      Fos. The results show that an average of 22% of all PNMT neurons in the C1
      region, 38% in C2 and 42% in the C3 region express estrogen receptor-alpha
      protein with the highest numbers of dual labeled neurons in the central levels of
      the C1-C3 regions. Overall, the percentages of dual labeled PNMT/ERalpha neurons
      did not change during the steroid-induced LH surge. In contrast, the percentage
      of c-Fos expressing PNMT neurons changed significantly during the LH surge. Thus,
      c-Fos immunoreactivity was highest in all three regions at 1200 h with 69% of the
      PNMT neurons in C1, 60% in C2 and 79% in C3 co-expressing c-Fos. C-Fos expression
      was lowest before and after the surge with 39% of the PNMT neurons in the C2
      region containing c-Fos at 0800 h, 52% c-Fos-positive PNMT neurons in C1 and 54%
      in area C3. The results show that many adrenergic neurons are direct targets for
      estradiol and that most PNMT neurons in the brainstem are activated during the
      initiation of the steroid-induced LH surge which suggests that epinephrine is one
      of the triggers that stimulates GnRH release during the surge.

PMID- 10967300
TI  - Chronic inhibition of Ca(2+)/calmodulin kinase II activity in the pilocarpine
      model of epilepsy.
AB  - The development of symptomatic epilepsy is a model of long-term plasticity
      changes in the central nervous system. The rat pilocarpine model of epilepsy was
      utilized to study persistent alterations in calcium/calmodulin-dependent kinase
      II (CaM kinase II) activity associated with epileptogenesis. CaM kinase II
      dependent substrate phosphorylation and autophosphorylation were significantly
      inhibited for up to 6 weeks following epileptogenesis in both the cortex and
      hippocampus, but not in the cerebellum. The net decrease in CaM kinase II
      autophosphorylation and substrate phosphorylation was shown to be due to
      decreased kinase activity and not due to increased phosphatase activity. The
      inhibition in CaM kinase II activity and the development of epilepsy were blocked
      by pretreating seizure rats with MK-801 indicating that the long-lasting decrease
      in CaM kinase II activity was dependent on N-methyl-D-aspartate receptor
      activation. In addition, the inhibition of CaM kinase II activity was associated
      in time and regional localization with the development of spontaneous recurrent
      seizure activity. The decrease in enzyme activity was not attributed to a
      decrease in the alpha or beta kinase subunit protein expression level. Thus, the
      significant inhibition of the enzyme occurred without changes in kinase protein
      expression, suggesting a long-lasting, post-translational modification of the
      enzyme. This is the first published report of a persistent, post-translational
      alteration of CaM kinase II activity in a model of epilepsy characterized by
      spontaneous recurrent seizure activity.

PMID- 10967301
TI  - Effects of calcium on the discharge pattern of primary and secondary endings of
      isolated cat muscle spindles recorded under a ramp-and-hold stretch.
AB  - The impulse activity of muscle spindles isolated from the cat tenuissimus muscle
      was investigated under varying concentrations of external calcium (Ca(2+)). The
      outer capsule of the muscle spindle represents an effective diffusion barrier for
      Ca(2+) ions since activity changes were strong and rapid only if the capsule was
      partly removed from the sensory region of the receptor. The impulse activity of
      both primary and secondary muscle spindle endings was lowered by an increase in
      the external Ca(2+) concentration from 1.8 mM (normal Ringer's solution) to 2.7
      mM and raised by a decrease in the Ca(2+) concentration from 1.8 to 0.9 mM.
      Primary endings were generally more strongly affected than secondary endings.
      With primary endings the firing rate changed by 23-52% when the external Ca(2+)
      concentration was altered by 0.9 mM. With secondary endings the discharge
      frequency changed by 15-24%. The afferent discharge patterns were obtained under
      repetitive ramp-and-hold stretches and were analyzed with regard to influences of
      external Ca(2+) ions on the static and dynamic components of the endings'
      responses. The stretch sensitivity and the adaptive response of both types of
      ending increased in the low Ca(2+) solution and decreased in the high Ca(2+)
      solution, but a specific effect on a single component of the responses to stretch
      was not observed. These findings indicate an overall change in excitability when
      the external Ca(2+) concentration was varied. The mechanical properties of the
      receptor were probably not affected since changes in the Ca(2+) concentration did
      not elicit a contraction or relaxation of the intrafusal muscle fibers. On the
      one hand, the observed effects can be explained according to the surface
      potential theory by an indirect influence of extracellular Ca(2+) ions on ion
      channels of the sensory nerve terminals, with Ca(2+) ions binding to negative
      charged sites at the endings' outer membrane. On the other hand, the results are
      consistent with the supposition that Ca(2+) ions act directly on ion channels of
      the sensory membrane of muscle spindle endings.

PMID- 10967302
TI  - Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain.
AB  - A high fat diet leads to progressive development of obesity and leptin resistance
      in C57 mice with a middle stage of peripheral, but not central, leptin
      resistance. This stage is characterized by increased fat accumulation despite
      relative hypophagia. At a later stage central leptin resistance ensues along with
      hyperphagia, rapid weight and fat gain. The aim of this study is to characterize
      the mRNA levels of leptin receptor (LR), neuropeptide Y (NPY) and pro
      opiomelanocortin (POMC) in high fat (HFF) and low fat (LFF) fed groups of mice.
      The hypothalamic arcuate nucleus (Arc) was investigated, as was the choroid
      plexus (ChP) in the case of the leptin receptor. No differences between groups
      were seen in LR, NPY or POMC mRNA levels after 1 week of feeding. After 8 and 19
      weeks, the HFF mice, compared to LFF controls, demonstrated a +45% (P<0. 003) and
      +84% (P<0.0001) increase in the ratio of visceral fat to body weight and +223%
      (P<0.0001) and +468% (P<0.0001) elevation in plasma leptin levels, respectively.
      At 8 weeks, LR mRNA expression showed a +98% (P<0.016) and +66% (P<0.0001)
      increase in ChP and Arc, respectively, while Arc NPY mRNA showed down-regulation
      by -45% (P<0. 006). Arc POMC mRNA showed no significant changes between groups at
      8 weeks. However, after long-term (19 weeks) feeding, the HFF mice displayed
      significantly -26% (P<0.039) and -33% (P<0.0015) reduced LR mRNA in the ChP and
      Arc, respectively, with Arc POMC and NPY mRNAs down by -55% (P<0.004) and -32%
      (P<0.009), respectively. The present results suggest that in the middle stage of
      development of high fat-induced obesity, when central leptin sensitivity is
      maintained, the increased leptin receptor expression may play a role to defend
      against obesity which is overwhelmed as central leptin insensitivity develops. In
      this later stage the down-regulation of the POMC system may be important in the
      final breakdown of weight homeostasis.

PMID- 10967303
TI  - Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of
      brain injury.
AB  - There is evidence that the excessive generation of reactive-oxygen radicals
      contributes to the brain injury associated with transient, cerebral ischemia.
      This study investigates the effects of tempol, a small, water-soluble molecule,
      that crosses biological membranes, on the brain injury caused by bilateral
      occlusion and reperfusion of both common carotid arteries in the gerbil (BCO).
      Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prior to reperfusion
      and at 1 and 6 h after the onset of reperfusion) reduced the formation of post
      ischemic brain oedema. Tempol also attenuated the increase in the cerebral levels
      of malondialdehyde (MDA) and the hippocampal levels of myeloperoxidase (MPO)
      caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of
      the hippocampal region of brains subjected to ischemia-reperfusion exhibited
      positive staining for nitrotyrosine (an indicator of the generation of
      peroxynitrite) and poly(ADP-ribose) synthetase (PARS) (an indicator of the
      activation of this nuclear enzyme secondary to single strand breaks in DNA). In
      gerbils subjected to BCO, which were treated with tempol, the degree of staining
      for nitrotyrosine and PARS was markedly reduced. Tempol increased survival and
      reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration)
      caused by cerebral ischemia and reperfusion. The loss of neurons from the
      pyramidal layer of the CA1 region caused by ischemia and reperfusion was also
      attenuated by treatment of gerbils with tempol. This is the first evidence that
      the membrane-permeable, radical scavenger tempol reduces the cerebral injury
      caused by transient, cerebral ischemia in vivo.

PMID- 10967304
TI  - Restraint as a stressor in mice: against the dopaminergic neurotoxicity of D
      MDMA, low body weight mitigates restraint-induced hypothermia and consequent
      neuroprotection.
AB  - In experimental studies of stress, restraint of laboratory rodents, perceived as
      easy to apply and believed to be reproducible, is a commonly used manipulation.
      The restraint manipulation is utilized as a technique to characterize the
      physiological, cellular and molecular consequences of stress as well as a tool to
      understand the ways in which stress may interact with toxic substances. In
      previous work, we utilized restraint in an examination of the effect of stress on
      the striatal dopaminergic neurotoxicity engendered by a series of substituted
      amphetamines. Contrary to our expectations, and most likely due to its body
      temperature-reducing properties in the mouse, restraint provided total or near
      total protection against the neurotoxicity of these agents. During subsequent
      studies utilizing C57Bl6/J female mice of varying weights and ages the degree of
      temperature reduction and the associated ability to block (20-100%) the dopamine
      depletion associated with the neurotoxic amphetamine 3,4-methylendioxyamphetamine
      (D-MDMA, 20 mg/kg of mouse body weight, every 2 h, s.c., total of four doses)
      were found to vary considerably more than had been previously observed. An in
      depth analysis of the role mouse weight plays in the temperature reduction
      induced by restraint indicates mouse weight is a primary determinant of
      hypothermia and subsequent neuroprotection. It suggests the induction of stress
      in rodents by restraint is a complex effect that may lead to unanticipated
      results. The restraint manipulation is not as straight-forward a procedure as is
      commonly believed. Our data indicate that consistent application of restraint may
      require an adjustment of the restrainer device to mouse body weight.

PMID- 10967305
TI  - Glutamatergic transmission in the trigeminal nucleus assessed with local blood
      flow.
AB  - Stimulation of the superior sagittal sinus in humans is pain-producing and in
      experimental animals leads to excitation of neurons in the caudal trigeminal
      nucleus and dorsal horns of the C(1/)C(2) cervical spinal cord: the
      trigeminocervical complex. Neuronal excitation is generally associated with an
      increase in local blood flow due to flow/metabolism coupling and we have used
      local blood flow in the trigeminocervical complex to examine the role of N-methyl
      D-aspartate (NMDA)-mediated transmission in these neurons. Cats were
      anaesthetised with alpha-chloralose (60 mg/kg, ip; supplements 20 mg/kg iv) after
      surgical preparation under halothane (0.5-3%). Animals were paralysed with
      gallamine triethiodide to prevent possible movement artefact distorting the laser
      Doppler signals. The superior sagittal sinus was isolated for electrical
      stimulation (150 V; 250 microsec duration; 0.5, 1, 2, 5, 10 and 20 Hz) and the
      dorsal surface of the spinal cord exposed at the C(2) level. Blood flow was
      recorded from the region over the trigeminocervical complex by careful placement
      of a laser Doppler flow probe. Flow was recorded continuously by an online
      collection programme and NMDA-mediated transmission modulated by intravenous
      administration of MK-801 (0.4, 1 and 4 mg/kg, iv) at the stimulation frequency of
      5 Hz. Stimulation of the superior sagittal sinus produced a stimulus-locked,
      frequency-dependent increase in blood flow in the region of the trigeminocervical
      complex. The mean maximum response was 39+/-4% at 20 Hz. MK-801 had no effect on
      the resting flow signal but markedly attenuated the SSS-evoked response in a dose
      dependent manner. The mean maximum response after 4 mg/kg MK-801 was 13+/-2%.
      NMDA-mediated transmission is likely to be involved in nociceptive
      trigeminovascular transmission within the trigeminocervical complex and offers a
      possible target for both acute and preventative treatment of migraine.

PMID- 10967306
TI  - Sexual dimorphism in the subiculum of the rat hippocampal formation.
AB  - Data accumulated over the last years demonstrate that the hippocampal formation
      of rodents is sexually dimorphic with respect to its functional attributes.
      Neuroanatomical substrates that might contribute to explain these gender-related
      differences have been described in the dentate gyrus, and in the CA3 and CA1
      hippocampal fields. However, the subiculum, the source of the major efferent
      projection of the hippocampal formation, has not been searched for the presence
      of sex-related differences. To address this issue, we have used stereological
      methods applied to adult rats of both sexes to estimate the volume of the
      subiculum, the total number of subicular neurons, and the total number and size
      of the synapses established by subicular neurons. The apical dendritic trees of
      Golgi-impregnated subicular neurons were also quantitatively analyzed. We have
      found that the volume of the subiculum and of its neuronal layer, and the total
      number of subicular neurons were greater in males than in females. Conversely,
      the total dendritic length of the apical arborization of the subicular neurons,
      and the number of dendritic spines and axospinous synapses were higher in females
      than in males. However, the size of the postsynaptic densities of the individual
      synapses was smaller in female than in male rats and, as a result, the surface
      area of the total active synaptic zones did not differ between the sexes. These
      findings provide an additional morphological clue for the comprehension of the
      sex dimorphisms within the hippocampal circuitries and, consequently, for a
      better understanding of the functional sex differences ascribed to the
      hippocampal formation.

PMID- 10967307
TI  - Synaptic relationship of the neurons containing a metabotropic glutamate
      receptor, MGluR5, with nociceptive primary afferent and GABAergic terminals in
      rat spinal superficial laminae.
AB  - Recent pharmacological evidence showed that metabotropic glutamate receptors
      (mGluRs), particularly mGluRs1/5, had a potential role in spinal nociceptive
      processing. However, previous morphological studies on mGluRs have been limited
      mainly to their distribution in the spinal cord. In the present study, electron
      microscopic immunocytochemistry was employed to identify the synaptic
      relationship of the neurons containing mGluR5, with nociceptive primary afferent
      and gamma-aminobutyric acid-ergic (GABAergic) terminals in the superficial dorsal
      horn of the spinal cord. Nociceptive C- and A(delta)-primary afferent terminals
      selectively labeled with horseradish peroxidase conjugated to wheat-germ
      agglutinin were in asymmetric synaptic contacts with or in direct apposition to
      mGluR5 positive dendritic profiles. The double-labeling studies revealed that
      mGluR5 immunoreactive dendrites also received symmetric synaptic contacts from
      axon terminals labeled with immunogold particles indicating GABA. The present
      demonstration of mGluR5 neurons receiving inputs from both nociceptive primary
      afferents and GABAergic terminals of presumed interneurons further supports the
      involvement of mGluR5 in the transmission and modulation of nociceptive
      information in the spinal cord.

PMID- 10967308
TI  - NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell
      size and protects from age-related, spatial memory deficits in middle-aged rats.
AB  - Administration of nerve growth factor (NGF) by intracerebroventricular infusion
      or transplantation of NGF-secreting cells to the basal forebrain improves spatial
      memory in aged animals. Using the adeno-associated virus (AAV) vector system,
      basal forebrain neurons were transduced to produce NGF ectopically for long
      intervals (at least 9 months). Rats received intraseptal injections of either the
      control vector, pTR-UF4, or the pTR-NGFmyc at 3 months of age, prior to testing
      their performance in the Morris water task. An age-related decrease in the
      acquisition of the hidden platform location was found at 12 months of age in the
      pTR-UF4 control group, but not in the pTR-NGFmyc group. Further, when compared to
      3 month old untreated animals, the control group, but not the pTR-NGFmyc group,
      was impaired at 12 months of age. Concomitant to preventing age-related memory
      deficits, the NGF gene transfer increased cholinergic neuron size by 34% in the
      medial septum. This approach may therefore represent a viable therapy for age
      related dementia involving dysfunction in cholinergic activity and memory, such
      as Alzheimer's disease.

PMID- 10967309
TI  - 5-HT(1A) and 5-HT(7) receptor expression in the mammalian retina.
AB  - Serotonin or 5-hydroxytryptamine (5-HT) is a common neurotransmitter found widely
      in the nervous system. Here, using RT-PCR, we have identified both the 5-HT(1A)
      and 5-HT(7) receptor transcripts in the rabbit retina. Furthermore, we found the
      same two receptors in the rat retina which was previously believed not to have a
      serotoninergic system. These results confirm previous reports of 5-HT(7) gene
      expression in retina and together with other biochemical, physiological and
      anatomical studies, they support the presence of multiple 5-HT receptors in the
      mammalian retina and suggest that the action of serotonin in the retina may be
      more complicated than previously believed.

PMID- 10967310
TI  - Modulation of K(+)-induced synaptosomal calcium influx by gabapentin.
AB  - Gabapentin, a drug useful in several neurological and psychiatric disorders,
      decreased K(+) (15 mM)-induced [Ca(2+)](i) increase in Fura-PE3-loaded rat
      neocortical synaptosomes (IC(50)=9.7 microM; submaximal inhibition of 28.6%).
      This effect may indicate a selective modulation of presynaptic Ca(2+) influx in
      response to depolarizing (pathological) conditions causing excessive
      neurotransmitter release.

PMID- 10967311
TI  - Identification of a protein phosphorylated by cAMP-dependent protein kinase in
      drosophila brain.
AB  - In the present study, we examined the effects of reagents that elevate cAMP
      concentration on protein phosphorylation in Drosophila brain cells. Application
      of forskolin or dopamine to brain cells that were prelabeled with (32)Pi enhanced
      phosphorylation of a 25-kDa protein (p25a). To identify p25a, we isolated the
      protein, and partial amino acid sequences were analyzed. Database searches showed
      that p25a is a J-domain protein, dJDP that contains the J-domain found in the
      DnaJ (heat shock protein 40) family of molecular chaperones.

PMID- 10967312
TI  - Immunohistochemical study on the distribution of six members of the Kv1 channel
      subunits in the rat basal ganglia.
AB  - The differential expression of specialized voltage-gated potassium (Kv) channel
      subtypes in the nervous system probably reflects the wide range of functions.
      Although there have been previous reports in the cellular and subcellular
      localizations of various Kv mRNAs and proteins, the comprehensive study described
      here is the first in which the expression of six Kv1 channel subunits have been
      directly compared in the rat basal ganglia. In the present study, we have found
      that staining patterns of the six Kv1 channel subunits overlap in some areas of
      the basal ganglia, but each has a unique pattern of expression. It was noted that
      Kv 1.4 subunit had a strikingly high level of expression in the globus pallidus
      compared to the caudate-putamen. This distinct distribution formed the clear
      demarcations between caudate-putamen and globus pallidus. The dot-like staining
      pattern of Kv1 subunits was observed through the accumbens nucleus. Strong
      staining for Kv1.4 was observed in the cerebral peduncle, not in the subthalamic
      nucleus. In the substantia nigra, immunoreactivity for Kv1.4 subunit was
      prominent in the pars reticulata of the substantia nigra. The staining intensity
      for Kv1.2 was high in the pars compacta of the substantia nigra. Our
      immunohistochemical results may support the notion that the formation of
      heteromultimeric Kv channels possibly represents an important contribution to the
      generation of Kv channel diversity in the brain, especially in the basal ganglia.

PMID- 10967314
TI  - Morphological and electrophysiological properties of dissociated primate retinal
      cells.
AB  - Although isolated retinal cell preparations have been used widely to study
      retinal function in lower vertebrates, dissociated cells from primate retina have
      not been developed for routine physiological experiments. In this study, we
      demonstrated the feasibility of obtaining viable and identifiable dissociated
      cells from the primate retina. In addition, we characterized voltage-dependent
      membrane currents in each type of primate retinal cell with the whole-cell patch
      clamp technique. Multiple types of ionic conductance with distinctive current
      profiles were recorded in various types of primate retinal neurons.
      Photoreceptors exhibited an inward I(H) activated by membrane hyperpolarization
      and an outward current activated at depolarized potentials. Two types of
      potassium currents (transient potassium current, I(K(A)), and delayed rectifier
      potassium current, I(K(V))) were recorded from bipolar cells. I(K(A)) dominated
      the current response in putative midget bipolar cells, and I(K(V)) was mainly
      associated with putative rod bipolar cells. L-type calcium currents (I(Ca)) were
      observed in primate bipolar cells with axon terminals, but not in axotomized
      bipolar cells. Large voltage-dependent sodium currents (I(Na)) were only recorded
      from ganglion cells. Muller cells exhibited I(K(V)) and large potassium inward
      rectifier current (I(K(IR))), and occasionally a small I(Na). Neurons with
      electrophysiological signatures of amacrine cells and horizontal cells were also
      studied even though their morphological features were lost during cell
      dissociation. By using both morphological and physiological criteria outlined in
      this report, it is possible to use the dissociated retinal cell preparation as an
      in vitro system for physiological, biochemical and pharmacological studies of the
      primate visual system.

PMID- 10967313
TI  - Rat hippocampal slices need bicarbonate for the recovery of synaptic transmission
      after anoxia.
AB  - The purpose of this study was to see how the nominal removal of bicarbonate (HCO(
      )(3)) from the extracellular space of brain tissue influenced recovery of brain
      tissue from anoxia. Removal of HCO(-)(3) in HEPES-buffered artificial
      cerebrospinal fluid (aCSF) inhibited almost completely recovery of synaptic
      transmission in hippocampal slices after anoxia. Altered pH did not contribute to
      this finding because adjusting intracellular (pH(i)) and extracellular (pH(o)) pH
      to control levels did not reduce the effect of HCO(-)(3) removal. Our results
      suggest that HCO(-)(3) levels are important in determining the extent of anoxic
      or ischemic brain injury.

PMID- 10967316
TI  - Chronic corticosterone enhances the rewarding effect of hypothalamic self
      stimulation in rats.
AB  - Excessive levels of glucocorticoids have been implicated in the etiology of
      affective disorders in humans, and in a range of behavioral deficits in animals.
      In the present study, we used an established regimen of corticosterone
      administration (40 mg/kg, for 21 days) to determine its effects upon responding
      for rewarding brain stimulation in rats. After chronic treatment, subjects
      exhibited an unexpected but significantly increased sensitivity to the rewarding
      effects of brain stimulation. These results suggest that chronic, high levels of
      corticosterone are unlikely to cause anhedonia in rodents.

PMID- 10967315
TI  - Dietary arginine alters time of symptom onset in Huntington's disease transgenic
      mice.
AB  - Recent neuroimaging studies reported complex changes in cerebral blood flow (CBF)
      in early-staged Huntington's disease (HD) patients. Deckel and co-workers [Deckel
      and Duffy, Brain Res. (in press); Deckel and Cohen, Prog. Neuro-Psychopharmacol.
      Biol. Psychiatry 24 (2000) 193; Deckel et al., Neurology 51 (1998) 1576; Deckel
      et al., J. Nucl. Med. 41 (2000) 773] suggested that these findings might be
      accounted for, in part, by alterations in cerebral nitric oxide (NO) and its
      byproduct, peroxynitrite. The current experiment tested this hypothesis by
      altering NO levels via manipulations of dietary L-arginine (ARG), the dietary
      precursor of NO, in mice transgenic for HD. Seventy-one mice were assigned at 12
      weeks of age to one of three isocaloric diets that varied in their content of
      ARG. These diets included: (a) 0% ARG, (b) 1.2% ARG (i.e. typical mouse chow), or
      (c) 5% ARG. The 5% ARG diets in HD mice accelerated the time of onset of body
      weight loss (P<0.05) and motor impairments (P<0.05), and increased resting CBF in
      HD relative to control (P<0.05). Conversely, the 0% ARG diet demonstrated no loss
      of body weight and had no changes in CBF relative to controls. However, the 0%
      ARG HD group continued to show significant deficits on motor testing (P<0. 05).
      The 1.2% ARG HD group showed reduced body weight loss, better motor functioning,
      and fewer changes in CBF compared to the 5% ARG HD group. Immunocytochemistry
      analysis found greater deposition of nitrotyrosine in the cortex, and
      vasculature, of HD+ mice, 5% and 1. 2%>0% arginine diets. When collapsed across
      all conditions, CBF inversely correlated (P<0.05) both with the body weight and
      motor changes suggesting that changes in CBF are associated with behavioral
      decline in HD mice. Collectively, these findings indicate that dietary
      consumption of the NO precursor ARG has a measurable, but complex, effect on
      symptom progression in HD transgenic mice, and implicates NO in the
      pathophysiology of HD.

PMID- 10967317
TI  - Antioxidant defense against antidepressants in C6 and 1321N1 cells.
AB  - The effects of pretreatment with the antioxidants reduced glutathione (GSH),
      ascorbate (ASC), Trolox (TROL), and combined ascorbate and Trolox (ASC/TROL)
      exposure on the acute (24 h) toxicities (EC50 value) of the antidepressants
      amitriptyline, imipramine (tricyclic antidepressants), fluoxetine (a selective
      serotonin reuptake inhibitor; SSRI), and tranylcypromine (a monoamine oxidase
      inhibitor; MAOI) were determined in the rat (C6) glioma and human (1321N1)
      astrocytoma cell lines using the neutral red uptake assay. The effects of
      pretreatment with buthionine-[S, R]-sulfoximine (BSO), and manipulation of
      intracellular cyclic AMP (cAMP) using isoproterenol (beta-receptor agonist), 3
      isobutyl-1-methylxanthine (IBMX; a phosphodiesterase inhibitor), and dibutyryl
      cyclic AMP (dBcAMP; cAMP analogue) on antidepressant toxicity were also
      determined. Protective responses were observed after antioxidant treatments and
      manipulation of cAMP in both C6 cells pretreated with dBcAMP (+dBcAMP) and 1321N1
      cells not pretreated with dBcAMP (-dBcAMP), with a few exceptions in 1321N1 cells
      (-dBcAMP). Some protective responses occurred in C6 cells (-dBcAMP) and 1321N1
      cells (+dBcAMP) after isoproterenol and combined IBMX/isoproterenol pretreatment
      but not after just IBMX pretreatment. Pretreatment with BSO enhanced toxicity
      with the exception of fluoxetine. The antidepressants caused increases in
      intracellular GSH in the C6 cells at subcytotoxic concentrations, with decreases
      in GSH occurring at higher concentrations. Cytotoxicity of the antidepressants
      may be partly mediated through oxidative stress with alterations in signal
      transduction pathways.

PMID- 10967318
TI  - Glutathione depletion and the production of reactive oxygen species in isolated
      hepatocyte suspensions.
AB  - Diethyl maleate (DEM) (5 mM) and ethyl methanesulfonate (EMS) (35 mM) treatments
      rapidly depleted cellular reduced glutathione (GSH) below detectable levels (1
      nmol/10(6) cells), and induced lipid peroxidation and necrotic cell death in
      freshly isolated rat hepatocytes. In hepatocytes incubated with 2.5 mM DEM and 10
      mM EMS, however, the complete depletion of cellular GSH observed was not
      sufficient to induce lipid peroxidation or cell death. Instead, DEM- and EMS
      induced lipid peroxidation and cell death were dependent on increased reactive
      oxygen species (ROS) production as measured by increases in dichlorofluorescein
      fluorescence. The addition of antioxidants (vitamin E succinate and deferoxamine)
      prevented lipid peroxidation and cell death, suggesting that lipid peroxidation
      is involved in the sequence of events leading to necrotic cell death induced by
      DEM and EMS. To investigate the subcellular site of ROS generation, the
      cytochrome P450 inhibitor, SKF525A, was found to reduce EMS-induced lipid
      peroxidation but did not protect against the loss of cell viability, suggesting a
      mitochondrial origin for the toxic lipid peroxidation event. In agreement with
      this conclusion, mitochondrial electron transport inhibitors (rotenone,
      thenoyltrifluoroacetone and antimycin A) increased EMS-induced lipid peroxidation
      and cell death, while the mitochondrial uncoupler, carbonyl cyanide m
      chlorophenylhydrazone, blocked EMS- and DEM-mediated ROS production and lipid
      peroxidation. Furthermore, EMS treatment resulted in the significant loss of
      mitochondrial alpha-tocopherol shortly after its addition, and this loss preceded
      losses in cellular alpha-tocopherol levels. Treatment of hepatocytes with
      cyclosporin A, a mitochondrial permeability transition inhibitor, oxypurinol, a
      xanthine oxidase inhibitor, or BAPTA-AM, a calcium chelator, provided no
      protection against EMS-induced cell death or lipid peroxidation. Our results
      indicate that DEM and EMS induce cell death by a similar mechanism, which is
      dependent on the induction of ROS production and lipid peroxidation, and
      mitochondria are the major source for this toxic ROS generation. Cellular GSH
      depletion in itself does not appear to be responsible for the large increases in
      ROS production and lipid peroxidation observed.

PMID- 10967319
TI  - Nitration and hydroxylation of aromatic amino acid and guanine by the air
      pollutant peroxyacetyl nitrate.
AB  - Peroxyacetyl nitrate (PAN) is a common gaseous photochemical compound in polluted
      air and cigarette smog. The toxicity of PAN has been found to depend on three
      pathways: (1) its oxidizing property that mimics peroxide or peroxynitrite; (2)
      its nitrating and hydroxylating properties similar to peroxynitrite; and (3) its
      acetylating property like acetic anhydride. The present investigations were
      intended to focus on the reactions of PAN with aromatic amino acids and guanine.
      When PAN interacted with tyrosine and guanine the major products were 3
      nitrotyrosine, 3, 5-dinitrotyrosine, 8-hydroxyguanine and 8-nitroguanine. These
      compounds have been used as indicators for the presence of peroxynitrite in
      previous studies. When PAN interacted with phenylalanine, the products were 3
      nitrotyrosine, 4-nitrophenylalanine, p-tyrosine, o-tyrosine and m-tyrosine. 5
      Hydroxytryptophan is produced from the reaction of PAN with tryptophan.
      Furthermore, the formation of nitrated tyrosines was also found in the PAN
      treated HL-60 cells. A high yield of dityrosine was formed when PAN and
      peroxynitrite were reacted with tyrosine, probably through free radical
      oxidation. We also found that peroxynitrite and PAN are similar in their
      oxidizing activity. From these findings, we suggest that peroxynitrite may be
      considered as the reactive intermediate of PAN.

PMID- 10967321
TI  - Editorial.

PMID- 10967320
TI  - Toxicity of Trp-P-2 to cultured human and rat keratinocytes.
AB  - Keratinocytes cultured from human and rat epidermis exhibited strongly divergent
      sensitivities to toxicity from the heterocyclic amine food mutagen Trp-P-2. To
      find a biochemical basis for this difference, the cultured cells were compared in
      their expression of phase 1 and 2 biotransformation activities, mutagenic
      activation and macromolecular adducts. The human and early passage rat cells
      expressed similar levels of ethoxyresorufin O-deethylase and N-acetyl transferase
      activities, their microsomes were similarly active in inducing bacterial
      mutagenesis when incubated with Trp-P-2, and the keratinocytes accumulated
      similar levels of DNA adducts over a 4-day treatment period. However, the human
      cells expressed an order of magnitude higher cytosolic glutathione S-transferase
      activity than the rat cells, likely providing enhanced protection. Late passage
      rat epidermal cells were insensitive to Trp-P-2 toxicity, attributable to their
      rapid loss of measured cytochrome P450 activity. Rat esophageal and fore-stomach
      epithelial cells resembled late passage rat epidermal cells in their lack of
      sensitivity to Trp-P-2 toxicity and lack of P450 activity. Human esophageal
      epithelial cells expressed substantial P450 activity but, in contrast to human
      epidermal cells, were sensitive to Trp-P-2 toxicity. Thus keratinocytes provide a
      valuable system in which to examine the basis for species- and tissue-specific
      differences in toxicity from this carcinogenic heterocyclic amine.

PMID- 10967322
TI  - Gene expression profiling: monitoring transcription and translation products
      using DNA microarrays and proteomics.
AB  - Novel and powerful technologies such as DNA microarrays and proteomics have made
      possible the analysis of the expression levels of multiple genes simultaneously
      both in health and disease. In combination, these technologies promise to
      revolutionize biology, in particular in the area of molecular medicine as they
      are expected to reveal gene regulation events involved in disease progression as
      well as to pinpoint potential targets for drug discovery and diagnostics. Here,
      we review the current status of these technologies and highlight some studies in
      which they have been applied in concert to the analysis of biopsy specimens.

PMID- 10967323
TI  - Gene expression data analysis.
AB  - Microarrays are one of the latest breakthroughs in experimental molecular
      biology, which allow monitoring of gene expression for tens of thousands of genes
      in parallel and are already producing huge amounts of valuable data. Analysis and
      handling of such data is becoming one of the major bottlenecks in the utilization
      of the technology. The raw microarray data are images, which have to be
      transformed into gene expression matrices--tables where rows represent genes,
      columns represent various samples such as tissues or experimental conditions, and
      numbers in each cell characterize the expression level of the particular gene in
      the particular sample. These matrices have to be analyzed further, if any
      knowledge about the underlying biological processes is to be extracted. In this
      paper we concentrate on discussing bioinformatics methods used for such analysis.
      We briefly discuss supervised and unsupervised data analysis and its
      applications, such as predicting gene function classes and cancer classification.
      Then we discuss how the gene expression matrix can be used to predict putative
      regulatory signals in the genome sequences. In conclusion we discuss some
      possible future directions.

PMID- 10967324
TI  - Functional genomics by mass spectrometry.
AB  - Systematic analysis of the function of genes can take place at the
      oligonucleotide or protein level. The latter has the advantage of being closest
      to function, since it is proteins that perform most of the reactions necessary
      for the cell. For most protein based ('proteomic') approaches to gene function,
      mass spectrometry is the method of choice. Mass spectrometry can now identify
      proteins with very high sensitivity and medium to high throughput. New
      instrumentation for the analysis of the proteome has been developed including a
      MALDI hybrid quadrupole time of flight instrument which combines advantages of
      the mass finger printing and peptide sequencing methods for protein
      identification. New approaches include the isotopic labeling of proteins to
      obtain accurate quantitative data by mass spectrometry, methods to analyze
      peptides derived from crude protein mixtures and approaches to analyze large
      numbers of intact proteins by mass spectrometry directly. Examples from this
      laboratory illustrate biological problem solving by modern mass spectrometric
      techniques. These include the analysis of the structure and function of the
      nucleolus and the analysis of signaling complexes.

PMID- 10967325
TI  - Genome-wide protein interaction maps using two-hybrid systems.
AB  - Automated sequence technology has rendered functional biology amenable to genomic
      scale analysis. Among genome-wide exploratory approaches, the two-hybrid system
      in yeast (Y2H) has outranked other techniques because it is the system of choice
      to detect protein-protein interactions. Deciphering the cascade of binding events
      in a whole cell helps define signal transduction and metabolic pathways or
      enzymatic complexes. The function of proteins is eventually attributed through
      whole cell protein interaction maps where totally unknown proteins are partnered
      with fully annotated proteins belonging to the same functional category. Since
      its first description in the late 1980's, several versions of the Y2H have been
      developed in order to overcome the major limitations of the system, namely false
      positives and false negatives. Optimized versions have been recently applied at
      multi-molecular and genomic scale. These genome-wide surveys can be
      methodologically divided into two types of approaches: one either tests
      combinations of predefined polypeptides (the so-called matrix approach) using
      various short-cuts to speed up the process, or one screens with a given
      polypeptide (bait) for potential partners (preys) present in complex libraries of
      genomic or complementary DNA (library screening). In the former strategy, one
      tests what one knows, for example pair-wise interactions between full-length open
      reading frames from recently sequenced and annotated genomes. Although based on a
      one-by-one scheme, this method is reported to be amenable to large-scale genomics
      thanks to multicloning strategies and to the use of small robotics workstations.
      In the latter, highly complex cDNA or genomic libraries of protein domains can be
      screened to saturation with high-throughput screening systems allowing the
      discovery of yet unidentified proteins. Both approaches have strengths and
      drawbacks that will be discussed here. None yields a full proteome-wide screening
      since certain proteins (e.g. some transcription factors) are not usable in Y2H.
      Novel two-hybrid assays have been recently described in bacteria. Applications of
      these time- and cost-effective assays to genomic screening will be discussed and
      compared to the Y2H technology.

PMID- 10967327
TI  - Recent developments and future directions in computational genomics.
AB  - Computational genomics is a subfield of computational biology that deals with the
      analysis of entire genome sequences. Transcending the boundaries of classical
      sequence analysis, computational genomics exploits the inherent properties of
      entire genomes by modelling them as systems. We review recent developments in the
      field, discuss in some detail a number of novel approaches that take into account
      the genomic context and argue that progress will be made by novel knowledge
      representation and simulation technologies.

PMID- 10967326
TI  - Four years of post-genomic life with 6,000 yeast genes.
AB  - Four years after disclosure of the full yeast genome sequence, a series of
      resources including tens of thousands of mutant strains, plasmids bearing
      isolated genes and disruption cassettes are becoming publicly available.
      Deletions of each of the 6,000 putative yeast genes are being screened
      systematically for dozens of phenotypic traits. In addition, new global
      approaches such as DNA hybridization arrays, quantitative proteomics and two
      hybrid interactions are being steadily improved. They progressively build up an
      immense computation network of billions of data points which will, within the
      next decade, characterize all molecular interactions occurring in a simple
      eukaryotic cell. In this process of acquisition of new basic knowledge, an
      international community of over 1,000 laboratories cooperates with a remarkable
      willingness to share projects and results.

PMID- 10967328
TI  - Domain repertoires as a tool to derive protein recognition rules.
AB  - Several approaches, some of which are described in this issue, have been proposed
      to assemble a complete protein interaction map. These are often based on high
      throughput methods that explore the ability of each gene product to bind any
      other element of the proteome of the organism. Here we propose that a large
      number of interactions can be inferred by revealing the rules underlying
      recognition specificity of a small number (a few hundreds) of families of protein
      recognition modules. This can be achieved through the construction and
      characterization of domain repertoires. A domain repertoire is assembled in a
      combinatorial fashion by allowing each amino acid position in the binding site of
      a given protein recognition domain to vary to include all the residues allowed at
      that position in the domain family. The repertoire is then searched by phage
      display techniques with any target of interest and from the primary structure of
      the binding site of the selected domains one derives rules that are used to infer
      the formation of complexes between natural proteins in the cell.

PMID- 10967329
TI  - Convergent evolution with combinatorial peptides.
AB  - Once the sequence of a genome is in hand, understanding the function of its
      encoded proteins becomes a task of paramount importance. Much like the
      biochemists who first outlined different biochemical pathways, many genomic
      scientists are engaged in determining which proteins interact with which
      proteins, thereby establishing a protein interaction network. While these
      interactions have evolved in regard to their specificity, affinity and cellular
      function over billions of years, it is possible in the laboratory to isolate
      peptides from combinatorial libraries that bind to the same proteins with similar
      specificity, affinity and primary structures, which resemble those of the natural
      interacting proteins. We have termed this phenomenon 'convergent evolution'. In
      this review, we highlight various examples of convergent evolution that have been
      uncovered in experiments dissecting protein-protein interactions with
      combinatorial peptides. Thus, a fruitful approach for mapping protein-protein
      interactions is to isolate peptide ligands to a target protein and identify
      candidate interacting proteins in a sequenced genome by computer analysis.

PMID- 10967331
TI  - Decision of the asteroid Leptasterias polaris to abandon its prey when confronted
      with its predator, the asteroid Asterias vulgaris.
AB  - We examined the decision of the asteroid Leptasterias polaris to abandon its
      bivalve prey Spisula polynyma when confronted with the predatory asteroid
      Asterias vulgaris. The frequency of abandonment decreased as the proportion of
      prey ingested increased from 10 to 40%, and increased with further increases in
      proportion of prey ingested. The escape response of L. polaris appears to be a
      compromise between risk of predation and benefits of feeding. This increase in
      the frequency of abandonment as the prey became further consumed beyond 30-40%
      likely represented decreasing benefits in the face of continued risk of
      predation. We propose that the initial decrease in fleeing as the proportion of
      prey eaten increased from 10 to 40% was because of a decreasing costs in subduing
      the prey, as there was a coincident decrease in the proportion of prey which were
      still capable of holding their valves closed.

PMID- 10967330
TI  - Gene trap: a way to identify novel genes and unravel their biological function.
AB  - The gene trap methodology is a powerful tool to characterize novel genes and
      analyze their importance in biological phenomena. It is based on the use of mouse
      embryonic stem cells and reporter vectors designed to randomly integrate into the
      genome, tagging an insertion site and generating a mutation. Theoretically, all
      the 100,000 genes present in the mouse genome could be tagged and functionally
      inactivated at the same time. Here we describe the basic concepts and
      perspectives of this methodology and show some results obtained by the gene trap
      approach used to study molecular cascades in basic cell biology and in
      developmental processes.

PMID- 10967332
TI  - Nitrogen efflux from the sediments of a subtropical bay and the potential
      contribution to macroalgal nutrient requirements.
AB  - The concentration of dissolved inorganic nitrogen (DIN) in the porewaters of
      shallow-water tropical marine sediments can be as high as 50-100 uM, at sediment
      depths of shallow as 20 cm. These concentrations are at least two-orders of
      magnitude greater than the DIN concentration in the overlying water. High
      porewater concentrations, and the resulting concentration gradient, result in
      substantial efflux of DIN from the sediments to the water column. This sediment
      derived DIN may be an important nutrient source for benthic algae. In Kaneohe
      Bay, Hawaii, a mean ammonium efflux rate of 490 umolm(-2)day(-1) and a mean
      nitrate+nitrite efflux rate of 123 umolm(-2)day(-1) were measured on reef slopes
      in the habitat occupied by benthic algae. It has been demonstrated that this
      nutrient source is essential for the growth of at least one abundant alga,
      Dictyosphaeria cavernosa, and possibly others. The DIN concentrations in Kaneohe
      Bay sediment porewaters, and the rates of DIN efflux from those sediments, are
      greater than porewater concentrations and efflux rates reported for other, more
      pristine tropical sites. The rate of sedimentation of particulate nitrogen is
      similar to rates reported from other tropical lagoons, and about twice as high as
      the efflux rate of total dissolved nitrogen. Given the present low nutrient
      concentrations in the water column of the Bay, these results support the view
      that nutrient efflux from the benthos is in part responsible for the persistence
      of D. cavernosa on these reefs. It is possible that efflux of DIN from sediments
      may be responsible for sustained benthic algal productivity in similar habitats
      on other tropical reefs.

PMID- 10967333
TI  - Acute and acclimated digestive responses of the cockle Cerastoderma edule (L.) to
      changes in food quality and quantity. I. Feeding and absorption of biochemical
      components.
AB  - Cockles Cerastoderma edule were fed two different concentrations ( approximately
      0.8 and 2 mm(3) l(-1)) of two diets with different qualities ( approximately 10
      and 60% of organic content) which were achieved by mixing different proportions
      of ashed silt particles with cells of the microalgae Tetraselmis suecica.
      Clearance, ingestion and absorption rates of organic matter and biochemical
      components were measured after 3 days (acute response) and 11 days (acclimated
      response) of exposure to the diets. With low quality diets cockles were found to
      reject part of the filtered matter ( approximately 25-35%) through pseudofaeces
      production both in the acute and acclimated responses. In the acute response,
      absorption rate of organic matter was positively dependent on food quality and
      quantity, but the physiological response to increasing food concentrations
      differed with food quality: with low qualities, increasing absorption rate
      resulted from the simultaneous increase of clearance ( approximately 2 times) and
      ingestion rate ( approximately 4 times) as well as absorption efficiency of
      organic matter ( approximately 22%). However, those fed high qualities, were
      found to compensate increasing food concentration by reducing ( approximately
      50%) clearance rate. The resulting moderate increase of ingestion rate (
      approximately 1.6 times) was accompanied with a reduction in absorption
      efficiency ( approximately 20%). Irrespective of food quality and quantity,
      protein and lipids were absorbed, respectively, with the highest (from 61.7 to
      80.0%) and the lowest (from 42.6 to 66.8%) efficiency. Acclimated response was
      entirely affected by food quality: with low qualities, cockles greatly improved
      the energetic intake from available ration ( approximately 4 and 2 times, with
      low and high food concentrations, respectively). Both preingestive and digestive
      mechanisms were involved in this response: at the preingestive level, clearance
      rate and preingestive selection efficiency were significantly increased. At the
      digestive level, cockles were capable of maintaining absorption efficiency of
      organic matter with rising ingestion rate. On the contrary, acclimation to high
      quality diets brought about no significant increase in organic absorption rate:
      with low ration, clearance rate was kept constant, whereas with high ration the
      increase in clearance and ingestion rate ( approximately 2 times) promoted a
      compensatory reduction in absorption efficiency. However, the biochemical
      composition of the absorbed matter was found to be absolutely modified, both at
      low and high food rations, due to an strong reduction of lipid absorption
      efficiency. The observed modifications of absorption rate and/or the biochemical
      composition of the absorbed matter suggests the capability of cockles to adjust
      the digestive performance.

PMID- 10967334
TI  - Acute and acclimated digestive responses of the cockle Cerastoderma edule (L.) to
      changes in the food quality and quantity. II. Enzymatic, cellular and tissular
      responses of the digestive gland.
AB  - Cockles Cerastoderma edule were fed two different concentrations of two diets
      with different qualities which were achieved by mixing different proportions of
      ashed silt particles with cells of the microalgae Tetraselmis suecica. After 3
      days (acute response) and 11 days (acclimated response) of exposure to the diets,
      we analysed the digestive activity of the digestive gland using cyto-histological
      and enzymatic techniques. We measured (i) the volumetric fraction of digestive
      and basophilic cells in digestive tubules, (ii) the diverticular radius and the
      thickness of digestive epithelia, (iii) the stereological parameters
      characterizing the lysosomal system and, (iv) dry weight, soluble protein content
      and specific and total amylase, cellulase, laminarinase, and protease activities
      of the digestive gland. In the conditions of the present study, specific
      cellulase and laminarinase activities in the digestive gland of cockles were
      correlated with the volumetric fraction of basophilic cells (r=0.672 and 0.642,
      respectively), whereas the specific protease was highly correlated (r=0.866) with
      lysosomal volume density. The implications of these correlations are discussed in
      relation to the feeding and absorptive parameters reported in the preceding
      publication. In the acute response, adjustments of the synthesis of constituents
      of the lysosomal/proteolytic system of the digestive cells seemed to be the only
      mechanism operating at the digestive level to respond to the changes in food
      availability. Lysosomal volume density increased with rising ingestion rate of
      organic matter, however, the occurrence of a limit in this short-term tissular
      response would account for the recorded trade-off between absorption efficiency
      and ingestion rate with different food qualities. With regard to acclimation,
      food quality determined the nature of the response of the digestive gland. With
      low quality diets, a time-dependent capability of the digestive gland for
      intensifying lysosomal/proteolytic production explains the increase of food
      absorption rates that result from higher filtration and ingestion rates. With
      high quality food, digestive acclimation differed with food particle
      concentration: with low rations, in spite of constant morphometrical and
      stereological parameters, the significant changes in the absorptive balance of
      biochemical components suggests the existence of an increased production of
      lysosomes that promotes an accelerated turn-over rate of the digestive epithelia.
      With high food concentrations, this response was coupled with increased
      activities of cellulase and laminarinase enzymes, probably as a consequence of
      higher rates of enzyme secretions from basophilic cells.

PMID- 10967335
TI  - Shifting roles of heterotrophy and autotrophy in coral energetics under varying
      turbidity.
AB  - Suspended particulate matter (SPM) strongly alters the trophic environment of
      photosymbiotic aquatic organisms. At high particles loads, phototrophic energy
      gains can be diminished due to light absorption by suspended particles, and
      stress from particle abrasion or deposition on tissues. However, energy gains are
      enhanced if organisms are able to use SPM as a food source. For photosymbiotic
      benthic suspension feeders, increases in SPM concentrations may require both
      phototrophic and heterotrophic acclimation to sustain a positive energy balance.
      This study provides an experimental analysis of the effects of contrasting light
      and SPM regimes on the energy budget (scope for growth) of two zooxanthellate
      corals (Goniastrea retiformis and Porites cylindrica). Using a factorial design
      in a flow-through tank system, corals were exposed for 2 months to shaded and
      unshaded conditions (equivalent to 3-4 m depth at 4 and 16 mg dry weight SPM l(
      1), respectively) and a range of controlled SPM loads with a natural organic
      content ( approximately 3% w/w). In G. retiformis, rates of particle ingestion
      were a linear function of SPM concentration within a broad range (1-30 mg dry
      weight l(-1)). After 2 months of shading, photosynthetic acclimation was
      significant in G. retiformis, but did not compensate for the reduced light level,
      as daily respiration exceeded daily photosynthesis. However, in response to the
      prolonged shading, G. retiformis more than doubled its rate of particle feeding.
      At high SPM treatments (16 mg dw l(-1)), sediment feeding by this species
      compensated fully for the 35-47% lower phototrophy in the shaded treatment. Due
      to both photo- and heterotrophic plasticity, G. retiformis gained tissue and
      skeletal mass at all experimental levels of light and SPM. In contrast, rates of
      particle intake by P. cylindrica contributed <10% to the energy budget in shaded
      and <3% in unshaded conditions. Feeding rates of P. cylindrica were half
      saturated at approximately 3 mg dry weight l(-1), and four- to eight-fold lower
      than those of G. retiformis. Skeletal growth was sustained, but tissue mass and
      lipid contents declined in shaded and high-SPM treatments, and carbon loss due to
      shading by SPM was not compensated for by particle feeding. Thus, due to a lack
      of photo- and heterotrophic plasticity, periods of high turbidity resulted in
      energy deficiency in P. cylindrica, and high turbidity conditions appeared
      physiologically unsustainable for this species. This study is the first to show
      heterotrophic plasticity in a symbiotic coral, and to show that such plasticity
      can offset stress from high particle loads. It demonstrates that changes in the
      trophic mode of some coral species are a mechanism for sustaining a positive
      energy balance in turbid environments, thereby broadening their physiological
      niche.

PMID- 10967336
TI  - Evaluating whether velar lobe size indicates food limitation among larvae of the
      marine gastropod Crepidula fornicata.
AB  - Disproportionately large feeding structures have been used to infer food
      limitation in some marine invertebrate larvae, but few studies have investigated
      whether other factors alter larval morphology in similar ways. In this study,
      larvae of Crepidula fornicata were reared either at five different food
      concentrations of Isochrysis galbana (clone T-ISO) at a single temperature (22
      degrees C) (Experiments I and II); or on three different phytoplankton species
      (Isochrysis galbana, Dunaliella tertiolecta, and Pavlova lutheri) at both high
      and low concentrations at a single temperature (22 degrees C) (Experiment III);
      or at high and low concentrations of Isochrysis galbana at four different
      temperatures between 16 and 25 degrees C (Experiment IV). Shell lengths and velar
      lobe dimensions were determined for individual larvae at intervals to monitor
      relative rates of velar and shell growth. In addition (Experiment V), fast
      growing and slow growing larvae in Experiment I were examined separately to
      determine whether velar lobes developed at similar rates (relative to shell
      growth) for fast and slow growing larvae within individual cultures. In general,
      velar lobes grew significantly larger, relative to shell length, when larvae were
      reared at low food concentrations (P<0.0001); for larvae of similar shell length,
      the velar lobes of those fed 1x10(4) cells ml(-1) were on average 17.7% larger
      than those of larvae fed 18x10(4) cells ml(-1) of T-ISO. In contrast, larvae fed
      different phytoplankton species at equivalently high food concentrations did not
      differ in relative velum size (P=0.2666), even though shell growth rates differed
      significantly for larvae raised on the different diets, indicating substantial
      variation in food quality. We also found that relative rates of velum and shell
      growth differed among fast and slow growing individuals within treatments.
      Temperature had no significant effect on relative rates of velar and shell growth
      within the 16-25 degrees C range tested (P=0.121), but may have altered the
      relationship between food concentration and relative velar growth. These results
      indicate that dramatically reduced food concentration induces disproportionate
      growth in the velar lobes of C. fornicata, but that interpretation of data from
      field-collected individuals of this species will be made difficult by the
      potentially confounding effects of temperature, food quality, and differences in
      individual growth potential. Assessments of food limitation using morphological
      measurements for field-collected larvae will need to be supplemented with other
      indicators before convincing conclusions about the extent of food limitation in
      C. fornicata can be drawn.

PMID- 10967337
TI  - Plasticity of cardiorespiratory neural processing: classification and
      computational functions.
AB  - Neural plasticity, or malleability of neuronal structure and function, is an
      important attribute of the mammalian forebrain and is generally thought to be a
      kernel of biological intelligence. In this review, we examine some reported
      manifestations of neural plasticity in the cardiorespiratory system and classify
      them into four functional categories, integral; differential; memory; and
      statistical-type plasticity. At the cellular and systems level the myriad forms
      of cardiorespiratory plasticity display emergent and self-organization
      properties, use- and disuse-dependent and pairing-specific properties, short-term
      and long-term potentiation or depression, as well as redundancy in series or
      parallel structures, convergent pathways or backup and fail-safe surrogate
      pathways. At the behavioral level, the cardiorespiratory system demonstrates the
      capability of associative and nonassociative learning, classical and operant
      conditioning as well as short-term and long-term memory. The remarkable
      similarity and consistency of the various types of plasticity exhibited at all
      levels of organization suggest that neural plasticity is integral to
      cardiorespiratory control and may subserve important physiological functions.

PMID- 10967338
TI  - Neurotransmitters in central respiratory control.
AB  - A diverse group of processes are involved in central control of ventilation. Both
      fast acting neurotransmitters and slower acting neuromodulators are involved in
      the central respiratory drive. This review deals with fast acting
      neurotransmitters that are essential centrally in the ventilatory response to
      H(+)/CO(2) and to acute hypoxia. Data are reviewed to show that the central
      response to H(+)/CO(2) is primarily at sites in the medulla, the most prominent
      being the ventral medullary surface (VMS), and that acetylcholine is the key
      neurotransmitter in this process. Genetic abnormalities in the cholinergic system
      lead to states of hypoventilation in man and that knock out mice for genes
      responsible for neural crest development have none or diminished CO(2)
      ventilatory response. In the acute ventilatory response to hypoxia the afferent
      impulses from the carotid body reach the nucleus tractus solitarius (NTS)
      releasing glutamate which stimulates ventilation. Glutamate release also occurs
      in the VMS. Hypoxia is also associated with release of GABA in the mid-brain and
      a biphasic change in concentration of another inhibitory amino acid, taurine.
      Collectively changes in these amino acids can account for the ventilatory output
      in response to acute hypoxia. Future studies should provide more data on
      molecular and genetic basis of central respiratory drive and the role of
      neurotransmitter in this essential function.

PMID- 10967339
TI  - Breathing pattern in humans: diversity and individuality.
AB  - In adult awake human subjects at rest, there exists a diversity in the breathing
      pattern not only in terms of tidal volume and inspiratory and expiratory duration
      and derived variables (TTOT, VT/TI and TI/TTOT) but also in the airflow profile.
      Besides this diversity, in every recording of ventilation at rest in steady-state
      condition breath-to-breath fluctuations are observed in ventilatory variables.
      This variability is non random and may be explained either by a central neural
      mechanism or by instability in the chemical feedback loops. Beyond this
      variability, each individual appears to select one particular pattern among the
      infinite number of possible combination of ventilatory variables and airflow
      profile. This one particular pattern appears to be a relatively stable
      characteristic of an adult individual being reproducible in several conditions
      and above all, after a long period of time. Consequences of this individuality of
      breathing pattern are discussed with regard to the selection of control subjects
      for a study and also per se: are there physiological situations where differences
      may be observed solely because of the differences in the pattern of breathing?

PMID- 10967340
TI  - Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker
      network model.
AB  - We review a new unified model of respiratory rhythm generation - the hybrid
      pacemaker-network model. This model represents a comprehensive synthesis of
      cellular and network mechanisms that can theoretically account for rhythm
      generation in different functional states, from the most reduced states in the
      neonatal nervous system in vitro to the intact adult system in vivo. The model
      incorporates a critical neuronal kernel consisting of a network of excitatory
      neurons with state-dependent, oscillatory bursting or pacemaker properties. This
      kernel, located in the pre-Botzinger complex of the ventrolateral medulla,
      provides a rudimentary pacemaker network mechanism for generating an inspiratory
      rhythm, revealed predominately in functionally reduced states in vitro. In vivo
      the kernel is embedded in a larger network that interacts with the kernel via
      inhibitory synaptic connections that provide the dynamic control required for the
      evolution of the complete pattern of inspiratory and expiratory network activity.
      The resulting hybrid of cellular pacemaker and network properties functionally
      endows the system with multiple mechanisms of rhythm generation. New
      biophysically realistic mathematical models of the hybrid pacemaker-network have
      been developed that illustrate these concepts and provide a computational
      framework for investigating interactions of cellular and network processes that
      must be analyzed to understand rhythm generation.

PMID- 10967341
TI  - Control of the exercise hyperpnoea in humans: a modeling perspective.
AB  - Models of the exercise hyperpnoea have classically incorporated elements of
      proportional feedback (carotid and medullary chemosensory) and feedforward
      (central and/or peripheral neurogenic) control. However, the precise details of
      the control process remain unresolved, reflecting in part both technical and
      interpretational limitations inherent in isolating putative control mechanisms in
      the intact human, and also the challenges to linear control theory presented by
      multiple-input integration, especially with regard to the ventilatory and gas
      exchange complexities encountered at work rates which engender a metabolic
      acidosis. While some combination of neurogenic, chemoreflex and circulatory
      coupled processes are likely to contribute to the control, the system appears to
      evidence considerable redundancy. This, coupled with the lack of appreciable
      error signals in the mean levels of arterial blood gas tensions and pH over a
      wide range of work rates, has motivated the formulation of innovative control
      models that reflect not only spatial interactions but also temporal interactions
      (i.e. memory). The challenge is to discriminate between robust competing control
      models that: (a) integrate such processes within plausible physiological
      equivalents; and (b) account for both the dynamic and steady-state system
      response over a range of exercise intensities. Such models are not yet available.

PMID- 10967342
TI  - Determinants of ventilatory instability and variability.
AB  - This paper reviews the major mechanisms that can give rise to various forms of
      variability in the ventilatory pattern. First, an elevated controller gain,
      coupled with the presence of delays and response lags in the chemoreflex loops,
      can lead to instability in feedback control and give rise to periodic breathing.
      This form of ventilatory stability can be assessed quantitatively by employing
      the concept of 'loop gain'. Several different methods of estimating loop gain
      from steady state or dynamic respiratory measurements are discussed. An
      inherently stable respiratory control system can also exhibit periodic behavior
      due to the influence of primary fluctuations in sleep-wake state and other
      physiological variables, such as cardiac output and cerebral blood flow. Self
      sustained, irregular ventilatory fluctuations may be generated by nonlinear
      dynamic interactions between various components of the respiratory control
      system, such as the lung vagal afferents and the respiratory pattern generator,
      or through the propagation of stochastic disturbances around the chemoreflex
      loops.

PMID- 10967343
TI  - Respiratory neuronal assemblies.
AB  - This review describes results from in vivo experiments on brain stem network
      mechanisms that control breathing. Multi-array recording technology and
      computational methods were used to test predictions derived from simulations of
      respiratory network models. This highly efficient approach has the advantage that
      many simultaneously recorded neurons are subject to shared stimulus, history, and
      state-dependent conditions. Our results have provided evidence for concurrent or
      parallel network interactions in the generation and modulation of the respiratory
      motor pattern. Recent data suggest that baroreceptors, chemoreceptors,
      nociceptors, and airway cough receptors shape the respiratory motor pattern, at
      least in part, through a system of shared coordinated 'multifunctional' neurons
      distributed in the brain stem. The 'gravity method' for the analysis and
      representation of multi-neuron data has demonstrated respiratory phase-dependent
      impulse synchrony among neurons with no respiratory modulation of their
      individual firing rates. The detection of this emergent property motivated the
      development of pattern detection methods that subsequently identified repeated
      transient configurations of these 'correlational assemblies'. These results
      support the view that information can be 'coded' in the nervous system by spike
      timing relationships, in addition to firing rate changes that traditionally have
      been measured by neurophysiologists.

PMID- 10967344
TI  - The respiratory central pattern generator of Lymnaea: a model, measured and
      malleable.
AB  - Great progress has been made, and continues to be made in our understanding of
      the neuronal mechanisms underlying respiration in a wide variety of model
      systems. The central pattern generator (CPG) controlling aerial respiration in
      the pond-snail Lymnaea is a particularly well-studied model. Using in vitro and
      semi-intact preparations, the neural circuitry that controls aerial respiration
      has been characterized as consisting of three identified interneurons.
      Furthermore, insight has been gained into the behavioural, cellular and synaptic
      mechanisms by which this circuit controls respiratory rhythmogenesis. It has also
      been demonstrated that aerial respiratory behaviour can be modified both by
      experience and by environmental factors. Studies have shown that, in a
      behavioural hierarchy, respiration is subservient to the whole-body withdrawal
      response that respiratory behaviour can be modified through operant conditioning,
      and that respiratory behaviour is altered by hypoxia. Through research on the
      Lymnaea respiratory CPG we are coming to a better understanding of the
      construction and malleability of a CPG network. The malleability of this CPG is
      of particular interest. No longer can neuronal networks underlying respiratory
      behaviour be considered hard-wired; they have inherent plasticity.

PMID- 10967345
TI  - Cellular mechanisms of oxygen sensing at the carotid body: heme proteins and ion
      channels.
AB  - The purpose of this article is to highlight some recent concepts on oxygen
      sensing mechanisms at the carotid body chemoreceptors. Most available evidence
      suggests that glomus (type I) cells are the initial site of transduction and they
      release transmitters in response to hypoxia, which in turn depolarize the nearby
      afferent nerve ending, leading to an increase in sensory discharge. Two main
      hypotheses have been advanced to explain the initiation of the transduction
      process that triggers transmitter release. One hypothesis assumes that a
      biochemical event associated with a heme protein triggers the transduction
      cascade. Supporting this idea it has been shown that hypoxia affects
      mitochondrial cytochromes. In addition, there is a body of evidence implicating
      non-mitochondrial enzymes such as NADPH oxidases, NO synthases and heme
      oxygenases located in glomus cells. These proteins could contribute to
      transduction via generation of reactive oxygen species, nitric oxide and/or
      carbon monoxide. The other hypothesis suggests that a K(+) channel protein is the
      oxygen sensor and inhibition of this channel and the ensuing depolarization is
      the initial event in transduction. Several oxygen sensitive K(+) channels have
      been identified. However, their roles in initiation of the transduction cascade
      and/or cell excitability are unclear. In addition, recent studies indicate that
      molecular oxygen and a variety of neurotransmitters may also modulate Ca(2+)
      channels. Most importantly, it is possible that the carotid body response to
      oxygen requires multiple sensors, and they work together to shape the overall
      sensory response of the carotid body over a wide range of arterial oxygen
      tensions.

PMID- 10967346
TI  - Multiple sites for central chemoreception: their roles in response sensitivity
      and in sleep and wakefulness.
AB  - Central chemoreceptors appear to be widely distributed in the brainstem. Why are
      there so many central chemoreceptor sites? This review focuses on two hypotheses.
      (1) The high sensitivity of the respiratory control system as a whole to small
      changes in systemic P(CO(2)) results from an additive, or greater, effect of the
      multiple central chemoreceptor sites. Each site provides a fraction of the total
      response and, importantly, provides tonic excitatory input in eucapnia as well.
      (2) Individual central chemoreceptor sites vary in effectiveness depending on the
      arousal or vigilance state of the animal. For example, some sites are more
      important in wakefulness; others in sleep. Proof for these hypotheses depends
      critically on obtaining accurate measures of stimulus intensity at each
      chemoreceptor site in vivo.

PMID- 10967347
TI  - Functional synaptic connections among respiratory neurons.
AB  - This presentation focuses on the application of methods to determine functional
      connections between neurons in the respiratory network of adult decerebrate rats.
      We employ a general network investigation paradigm that first examines the
      intracellular recordings of a respiratory neuron and then determines which
      neurons synapse with it to produce the observed membrane potential changes. It is
      used to pursue the source of respiratory excitation and inhibition from its
      arrival at phrenic motoneurons to respiratory neurons in the medulla, and then
      examine some of the interactions among these neurons that shape their patterns of
      activity. Findings include a demonstration that phrenic motoneuron activity is
      determined by excitation from medullary inspiratory premotor neurons and
      inhibition by Botzinger complex expiratory neurons, and that the latter neurons
      inhibit both medullary inspiratory premotor neurons and themselves. We conclude
      that these functional interconnections explain the activity patterns of some
      respiratory neurons, but the connections between neurons thought to be involved
      in rhythm generation remain to be demonstrated in adult rats.

PMID- 10967348
TI  - Genetic and developmental models for the neural control of breathing in
      vertebrates.
AB  - The present paper reviews some of the possible mechanisms that may link gene
      function in the brainstem and breathing patterns in vertebrates. On one hand,
      adaptation and acclimatisation of mature breathing to environmental constraints
      such as hypoxia, involves complex regulation of the gene expression in precise
      cardiorespiratory sites of the brainstem. On the other hand, targeted
      inactivation of different genes suggests that postnatal respiratory variables at
      rest depend on genes controlling the prenatal development of the brainstem.
      During embryogenesis, neurotrophins (gdnf, bdnf) regulate the survival of
      specific cellular populations composing the respiratory neuronal network. The
      expression of developmental genes such as Hox and Krox-20 initiates hindbrain
      segmentation, the earliest sign of regionalisation in the brainstem. As shown in
      the chick embryo, segmental specifications allow the establishment of an active
      embryonic rhythmic network and later insertion of specific neuronal circuits
      increasing the primordial rhythm frequency to near mature values.

PMID- 10967349
TI  - Determinants of respiratory motoneuron output.
AB  - The respiratory motoneuron is the critical link between the neural elements
      responsible for respiratory rhythm generation and the respiratory muscles.
      Studies of respiratory motoneurons provide important information on the
      mechanisms that govern respiratory motor output because of the obligatory synapse
      that exists between these respiratory motoneurons and the respiratory muscle
      fibers they innervate. This review focuses almost exclusively upon one type of
      respiratory motoneuron, the hypoglossal motoneuron. Intrinsic properties
      (membrane properties and ion channels) as well as fast excitatory and inhibitory
      synaptic transmission to these motoneurons have been extensively studied during
      the last 10 years. This review summarizes many of these new findings. It is hoped
      that some of these findings can be generalized to all respiratory motoneurons and
      these will be of importance in formulating models that can predict the behavior
      of these critical elements in the respiratory system.

PMID- 10967350
TI  - Measuring ventilatory acclimatization to hypoxia: comparative aspects.
AB  - Acclimatization to hypoxia increases the hypoxic ventilatory response (HVR) in
      mammals. The literature on humans shows that several protocols can quantify this
      increase in HVR if isocapnia is maintained, regardless of the exact level of
      Pa(CO(2)). In rats, the isocapnic HVR also increases with chronic hypoxia and
      this cannot be explained by a non-specific effect of increased ventilatory drive
      on the HVR. Changes in arterial pH are predicted to increase the HVR during
      chronic hypoxia in rats but this has not been quantified. Limitations in
      determining mechanisms of change in the HVR from reflex experiments are
      discussed. Chronic hypoxia changes some, but not all, indices of ventilatory
      motor output that are useful for normalization between experiments on
      anesthetized rats. Finally, ducks also show time-dependent increases in
      ventilation during chronic hypoxia and birds provide a good experimental model to
      study reflex interactions. However, reflexes from intrapulmonary CO(2)
      chemoreceptors can complicate the measurement of changes in the isocapnic HVR
      during chronic hypoxia in birds.

PMID- 10967351
TI  - Wnt signaling function in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease with progressive dementia
      accompanied by three main structural changes in the brain: diffuse loss of
      neurons; intracellular protein deposits termed neurofibrillary tangles (NFT) and
      extracellular protein deposits termed amyloid or senile plaques, surrounded by
      dystrophic neurites. Two major hypotheses have been proposed in order to explain
      the molecular hallmarks of the disease: The 'amyloid cascade' hypothesis and the
      'neuronal cytoskeletal degeneration' hypothesis. While the former is supported by
      genetic studies of the early-onset familial forms of AD (FAD), the latter
      revolves around the observation in vivo that cytoskeletal changes - including the
      abnormal phosphorylation state of the microtubule associated protein tau - may
      precede the deposition of senile plaques. Recent studies have suggested that the
      trafficking process of membrane associated proteins is modulated by the FAD
      linked presenilin (PS) proteins, and that amyloid beta-peptide deposition may be
      initiated intracellularly, through the secretory pathway. Current hypotheses
      concerning presenilin function are based upon its cellular localization and its
      putative interaction as macromolecular complexes with the cell-adhesion/signaling
      beta-catenin molecule and the glycogen synthase kinase 3beta (GSK-3beta) enzyme.
      Developmental studies have shown that PS proteins function as components in the
      Notch signal transduction cascade and that beta-catenin and GSK-3beta are
      transducers of the Wnt signaling pathway. Both pathways are thought to have an
      important role in brain development, and they have been connected through
      Dishevelled (Dvl) protein, a known transducer of the Wnt pathway. In addition to
      a review of the current state of research on the subject, we present a cell
      signaling model in which a sustained loss of function of Wnt signaling components
      would trigger a series of misrecognition events, determining the onset and
      development of AD.

PMID- 10967352
TI  - Stress-induced relapse to heroin and cocaine seeking in rats: a review.
AB  - Studies in humans suggest that exposure to stress increases the probability of
      relapse to drug use, but until recently there has been no animal model to study
      the mechanisms that mediate this effect. We have developed a reinstatement
      procedure that allows us to study the effect of stress on relapse to drug seeking
      in rats. Using this procedure, we have shown that exposure to intermittent
      footshock stress reliably reinstates heroin and cocaine seeking after prolonged
      drug-free periods. In the present paper, we summarize results from several
      studies on stress-induced reinstatement of heroin and cocaine seeking in rats. We
      first assess the degree to which the phenomenon of stress-induced relapse
      generalizes to other stressors, to behaviors controlled by other drugs of abuse,
      and to behaviors controlled by non-drug reinforcers. We then review evidence from
      studies concerned with the neurotransmitters, the brain sites, and the neural
      systems involved in stress-induced reinstatement of drug seeking. Finally, we
      consider the mechanisms that might underlie stress-induced relapse to drug
      seeking and the possible implications of the findings for the treatment of
      relapse to drug use in humans.

PMID- 10967353
TI  - The suprachiasmatic nucleus and the circadian time-keeping system revisited.
AB  - Many physiological and behavioral processes show circadian rhythms which are
      generated by an internal time-keeping system, the biological clock. In rodents,
      evidence from a variety of studies has shown the suprachiasmatic nucleus (SCN) to
      be the site of the master pacemaker controlling circadian rhythms. The clock of
      the SCN oscillates with a near 24-h period but is entrained to solar day/night
      rhythm by light. Much progress has been made recently in understanding the
      mechanisms of the circadian system of the SCN, its inputs for entrainment and its
      outputs for transfer of the rhythm to the rest of the brain. The present review
      summarizes these new developments concerning the properties of the SCN and the
      mechanisms of circadian time-keeping. First, we will summarize data concerning
      the anatomical and physiological organization of the SCN, including the roles of
      SCN neuropeptide/neurotransmitter systems, and our current knowledge of SCN input
      and output pathways. Second, we will discuss SCN transplantation studies and how
      they have contributed to knowledge of the intrinsic properties of the SCN,
      communication between the SCN and its targets, and age-related changes in the
      circadian system. Third, recent findings concerning the genes and molecules
      involved in the intrinsic pacemaker mechanisms of insect and mammalian clocks
      will be reviewed. Finally, we will discuss exciting new possibilities concerning
      the use of viral vector-mediated gene transfer as an approach to investigate
      mechanisms of circadian time-keeping.

PMID- 10967354
TI  - Regulation of exocytosis in neuroendocrine cells: spatial organization of
      channels and vesicles, stimulus-secretion coupling, calcium buffers and
      modulation.
AB  - Neuroendocrine cells display a similar calcium dependence of release as synapses
      but a strongly different organization of channels and vesicles. Biophysical and
      biochemical properties of large dense core vesicle release in neuroendocrine
      cells suggest that vesicles and channels are dissociated by a distance of 100-300
      nm. This distinctive organization relates to the sensitivity of the release
      process to mobile calcium buffers, the resulting relationship between calcium
      influx and release and the modulatory mechanisms regulating the efficiency of
      excitation-release coupling. At distances of 100-300 nm, calcium buffers
      determine the calcium concentration close to the vesicle. Notably, the
      concentration and diffusion rate of mobile buffers affect the efficacy of
      release, but local saturation of buffers, possibly enhanced by diffusion
      barriers, may limit their effects. Buffer conditions may result in a linear
      relationship between calcium influx and exocytosis, in spite of the third or
      fourth power relation between intracellular calcium concentration and release.
      Modulation of excitation-secretion coupling not only concerns the calcium
      channels, but also the secretory process. Transmitter regulation mediated by cAMP
      and PKA, as well as use-dependent regulation involving calcium, primarily
      stimulates filling of the releasable pool. In addition, direct effects of cAMP on
      the probability of release have been reported. One mechanism to achieve increased
      release probability is to decrease the distance between channels and vesicles.
      GTP may stimulate release independently from calcium. Thus, while in most cases
      primary inputs triggering these pathways await identification, it is evident that
      large dense core vesicle release is a highly controlled and flexible process.

PMID- 10967356
TI  - Application of PET-MRI registration techniques to cat brain imaging.
AB  - In positron emission tomography (PET) studies of diseased animals, it is very
      useful to have accurate anatomical information as a reference. In human studies,
      anatomical information is usually obtained from magnetic resonance imaging (MRI)
      of the subject with retrospective registration of the subject's PET image to the
      MRI. A number of PET-MRI registration techniques are used for this purpose.
      However, the utility of these methods has not been tested for animals image
      registration. This paper studies the feasibility of applying two currently used
      human brain PET-MRI registration techniques to cat brain images. METHODS: Three
      cats were anesthetized with isoflurane gas, and PET images were acquired with
      H(2)(15)O, benzodiazepine receptor ligand 11C-flumazemil (FMZ), dopamine receptor
      ligand 11C-nemonapride (NEM) and fluorodeoxy glucose (18F-FDG). The four PET
      scans were acquired consecutively within the same day while the cat remained
      fixed in the scanner. We also obtained T1-weighted and T2-weighted MRI of the
      cats in a 4.7 T unit. The PET images were registered to MRI using two human brain
      registration techniques: a semi-automatic method (SAM), which is a two-step
      method based on the extraction of the midsagittal plane, and an automatic method
      (AMIR) method that minimizes PET pixel variance within spatially connected
      segments determined by MRI. RESULTS: T2-weighted MRI provided better structural
      information than T1 MRI. FMZ did, while FDG or H(2)O PET images did not, provide
      a structural outline of the brain. The FMZ PET image was registered to MRI
      satisfactorily using SAM. The striatum visualized in nemonapride PET image re
      sliced with the same parameters matched the striatum identified in T2-weighted
      MRI. Registration by AMIR was successful by inspection for FMZ, FDG or H(2)O PET
      images in only one of the three cats. The registration error of SAM was estimated
      to be less than 2 mm or 2 degrees. CONCLUSION: A satisfactory registration of FMZ
      PET to T2-weighted MRI of the cat brain was obtained by a two-step manual
      registration technique. This will enhance the usefulness of PET in the field of
      cerebral pathophysiology.

PMID- 10967355
TI  - Tau protein isoforms, phosphorylation and role in neurodegenerative disorders.
AB  - Tau proteins belong to the family of microtubule-associated proteins. They are
      mainly expressed in neurons where they play an important role in the assembly of
      tubulin monomers into microtubules to constitute the neuronal microtubules
      network. Microtubules are involved in maintaining the cell shape and serve as
      tracks for axonal transport. Tau proteins also establish some links between
      microtubules and other cytoskeletal elements or proteins. Tau proteins are
      translated from a single gene located on chromosome 17. Their expression is
      developmentally regulated by an alternative splicing mechanism and six different
      isoforms exist in the human adult brain. Tau proteins are the major constituents
      of intraneuronal and glial fibrillar lesions described in Alzheimer's disease and
      numerous neurodegenerative disorders referred to as 'tauopathies'. Molecular
      analysis has revealed that an abnormal phosphorylation might be one of the
      important events in the process leading to their aggregation. Moreover, a
      specific set of pathological tau proteins exhibiting a typical biochemical
      pattern, and a different regional and laminar distribution could characterize
      each of these disorders. Finally, a direct correlation has been established
      between the progressive involvement of the neocortical areas and the increasing
      severity of dementia, suggesting that pathological tau proteins are reliable
      marker of the neurodegenerative process. The recent discovery of tau gene
      mutations in frontotemporal dementia with parkinsonism linked to chromosome 17
      has reinforced the predominant role attributed to tau proteins in the
      pathogenesis of neurodegenerative disorders, and underlined the fact that
      distinct sets of tau isoforms expressed in different neuronal populations could
      lead to different pathologies.

PMID- 10967357
TI  - A double labeling technique using WGA-apoHRP-gold as a retrograde tracer and non
      isotopic in situ hybridization histochemistry for the detection of mRNA.
AB  - We describe a novel method to study the neurochemical nature of a specific
      neuronal pathway by using conjugated WGA-apoHRP as a retrograde tracer and non
      isotopic in situ hybridization histochemistry to examine the expression of mRNA.
      The technique was developed to eliminate the reduction of retrograde tracer
      during the rigorous procedures involved in in situ hybridization. The tracer was
      injected stereotaxically into the brainstem of Macaca fascicularis monkeys.
      Sections through the central nucleus of the amygdala were processed for the
      visualization of the retrogradely transported WGA-apoHRP-gold using a silver
      enhanced reaction, followed by non radioactive in situ hybridization for the mRNA
      encoding glutamic acid decarboxylase (GAD67). Numerous retrogradely labeled cells
      were observed in the central nucleus of the amygdala. Comparison of double
      labeled sections with sections processed for the retrograde tracer alone
      indicated that there was relatively little loss of the retrograde tracer during
      the in situ hybridization processing. This method provides a relatively simple
      and reliable tool to study the molecular phenotype of identified projection
      neurons.

PMID- 10967358
TI  - Light scattering in brain slices measured with a photon counting fiber optic
      system.
AB  - Measurements of intrinsic optical signals (IOSs) from neural tissue, commonly
      with a reflection-type or transmittance-type set-up, have been used increasingly
      to study physiological events. Even for the same event, however, such as
      spreading depression (SD) or osmotic challenge, signals of opposite polarities
      (increase or decrease) have been obtained by different investigators using
      similar set-ups under similar conditions. The origin of the inconsistencies is
      still unknown. It is suggested here that the inconsistencies may be caused by
      artifacts associated with tissue surface scattering. The main goal of this paper
      was to present a photon counting fiber optic (PCFO) system designed to exclude
      surface artifacts and predominantly measure the light scattering (LS) within the
      tissue. Experiments on rat neocortical slices under osmotic challenges
      demonstrated the consistency of the PCFO data: hypertonic challenge always
      increased LS signal while hypotonic challenge decreased it, as long as the
      challenge did not induce SD. Under strong osmotic challenge (-100 mOsm), the
      signal suddenly reversed the polarity at the onset of SD induced by the challenge
      and continued to increase until the challenge was removed. When SD was blocked by
      high [Mg(2+)](o), the LS signal remained decreased during the -100 mOsm
      challenge. A spectroscopic study with the PCFO system showed that the spectrum of
      tissue scattering was almost a flat function in most of the visible range (650
      470 nm) with a maximum at 500 nm and a rapid drop at 450 nm.

PMID- 10967359
TI  - Multi-electrode stimulation and recording in the isolated retina.
AB  - As part of an exploration of the feasibility of an epi-retinal prosthesis, we
      developed an experimental method to electrically stimulate and record from
      retinal neurons using a micro-fabricated multi-electrode array. An isolated
      retina is placed on an array of 10 microm diameter disk electrodes with the
      ganglion cell side of the retina facing the electrode surfaces. The retina is
      bathed in oxygenated Ames' medium and warmed in order to sustain it in vitro for
      the duration of an experiment, typically 4-9 h. To reduce stimulus artifacts, the
      electrodes are grouped into two clusters - one used for stimulation and the other
      for recording--spaced several hundred microns apart, and electrodes are insulated
      with both silicon nitride and a 10 microm thick layer of polyimide. Stimuli are
      delivered to the array using an optically isolated current source stimulator, and
      the resulting responses recorded with an eight channel nerve response amplifier.
      Stimulation and recording are performed under computer control. A variety of
      physiologic measurements is described in order to illustrate the strengths and
      drawbacks of this method.

PMID- 10967360
TI  - A computer program for sequencing and presenting complex sounds for auditory
      neuroimaging studies.
AB  - This paper describes a computer program, named ASAP (audio sequencing and
      presentation), that runs on IBM PC compatible hardware with a Microsoft Windows
      operating system and has been specially designed for facilitating auditory
      neuroimaging studies. The program's main characteristics are: (1) the ability to
      generate sequences of complex sounds; (2) an easy-to-use, graphical user
      interface; (3) full compatibility with Microsoft Windows 95 or later and Windows
      NT version 4.0 or later software; (4) precise timing of selected sound sequences;
      (5) the capability of triggering other devices; (6) the capability of being
      triggered to deliver stimuli; (7) support for both monotic and dichotic sound
      sequences; and (8) rudimentary support for the simultaneous presentation of
      pictures/text and sound.

PMID- 10967361
TI  - Simultaneous measurement of human joint force, surface electromyograms, and
      functional MRI-measured brain activation.
AB  - Functional magnetic resonance imaging (fMRI) has been increasingly used in
      studying human brain function given its non-invasive feature and good spatial
      resolution. However, difficulties in acquiring data from peripheral (e.g.
      information from muscle) during fMRI studies of motor function hinder
      interpretation of fMRI data and designing more sophisticated investigations. Here
      we describe a system that was designed to concurrently measure handgrip force,
      surface electromyograms (EMG) of finger flexor and extensor muscles, and fMRI of
      human brain. The system included a pressure transducer built in a hydraulic
      environment, a heavily shielded EMG recording element, and a visual feedback
      structure for online monitoring of force and/or EMG signal, by the subject
      positioned in the scanner during an fMRI experiment. System evaluation and
      subsequent fMRI motor function studies have indicated that by using this system,
      high quality force and EMG signals can be recorded without sacrificing the
      quality of the fMRI data.

PMID- 10967362
TI  - Tracking of flying insects using pan-tilt cameras.
AB  - Potent and affordable video and computer systems for automatic data acquisition
      are becoming increasingly important in behavioural neuroscience. It has remained
      challenging, however, to acquire data from small and fast-moving animals, such as
      insects in flight, due to the limited spatial and temporal resolution of the
      systems currently available. Our research on free-flying insects motivated the
      development of new methods in the context of two different experimental settings.
      First, the position and precise body axis direction of honey bees approaching a
      food source were automatically measured. Second, the flight trajectories of a
      phonotactic parasitoid fly homing in on its cricket host were recorded in 3D. We
      used pan-tilt cameras, i.e. cameras with moveable optics, to follow the animal's
      path with a close up image. Novel methods were developed for image acquisition
      and position measurement using pan-tilt cameras, as well as calibration and data
      evaluation in 3D world coordinates. The innovations of this system comprise: (1)
      Acquisition of images in high spatial detail over large observation areas. (2)
      Image acquisition at a field rate of 50 Hz PAL. (3) Free positioning of the
      cameras for 3D acquisition. (4) Computation of the flight path in 3D world
      coordinates. We illustrate the capabilities of the system with data obtained from
      a calibration object as well as from the behaviour of unrestricted, free-flying
      flies and bees. Potential applications in behavioural neuroscience and the
      psychophysics of sensory perception are briefly discussed.

PMID- 10967363
TI  - A novel system for simultaneous monitoring of locomotor and sound activities in
      animals.
AB  - This paper describes a PC-based system for simultaneous monitoring of locomotor
      and sound activities on small rodents. The displacement and location signals of
      the animal were first determined across consecutive video-frames, followed by
      marked data reduction to cater for long-term studies. At the same time, sounds
      generated by the animal were detected and the sound level was recorded as root
      mean-square values at 1 s intervals. Preliminary data showed that such a multi
      parametric monitor system could provide comprehensive information on the animal's
      activity.

PMID- 10967364
TI  - Effect of cocaine, nomifensine, GBR 12909 and WIN 35428 on carbon fiber
      microelectrode sensitivity for voltammetric recording of dopamine.
AB  - Electrochemical measurements using voltammetry or amperometry at carbon-fiber
      microelectrodes have been used in vitro and in vivo to examine regulatory
      mechanisms for the central dopamine system. In many of these experiments,
      dopamine efflux concentrations under control conditions are determined followed
      by their alterations in response to a drug treatment. The present study
      demonstrates that some drugs can affect dopamine measurements, not only by their
      expected pharmacological action but also by directly altering the microelectrode
      responsivity. The commonly used reuptake inhibitors GBR 12909 (10 microM) and
      nomifensine (5 microM) drastically reduce electrode sensitivity and, in the case
      of nomifensine, increase the time to reach a plateau in response to dopamine
      boluses (i.e. reduced 'frequency response'). Cocaine (10 microM) and WIN 35428 (2
      microM) have negligible effect on these indices. This decrease in sensitivity was
      found in both nafion and non-nafion coated electrodes. Further, the reduction in
      sensitivity seen in non-nafion coated electrodes was not prevented by increasing
      the reversal potential (from +1.0 to +1.3 V) and voltage scan rate (from 350 to
      450 V/s). These data suggest that care must be taken when interpreting data from
      voltammetric or amporometric experiments using carbon electrodes where GBR 12909
      or nomifensine are used, especially at high concentrations. Furthermore, wherever
      possible, direct effects of a drug on electrode sensitivity and frequency
      response should be determined.

PMID- 10967365
TI  - Neutral red as a hydrophobic probe for monitoring neuronal activity.
AB  - Neutral red fluorescence has been used to monitor neuronal activity. Local
      changes in either pH or hydrophobicity are reported to increase neutral red
      fluorescence, but the mechanisms underlying the increases remain unclear. In this
      study, the pH-dependent fluorescence changes in the basic and acidic forms of
      neutral red preloaded in rat cerebellar slices were separately measured with two
      excitation wavelengths. Bath application of kainate, domoate or alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) at 1 mM increased fluorescence
      of the acidic form and decreased that of the basic form irreversibly, consistent
      with a pH-dependent mechanism. In contrast, application of lower concentrations
      of AMPA, (S)-3,5-dihydroxyphenylglycine or KCl increased fluorescence of both
      forms transiently, suggesting that a pH-independent mechanism may also increase
      neutral red fluorescence. Electrical stimulation in the molecular layer also
      increased fluorescence of both forms. The response to weak electrical stimulation
      decayed in about 1 s, while response to intense stimulation lasted longer than 1
      min. Neutral red binding to phospholipids was also detected as fluorescent spots
      on thin-layer chromatography, suggesting that interaction with phospholipids
      enhances neutral red fluorescence. Thus, the short-lasting signal of neutral red
      suggests its usage as a hydrophobic probe for neuronal activity.

PMID- 10967367
TI  - Correlates of symptomatic, minor and major depression in the elderly.
AB  - BACKGROUND: Associations between different types of depression with clinical
      characteristics and putative vulnerability factors from several domains (health,
      disability, personality, familial psychopathology) were studied in a sample of
      elderly subjects, in order to find arguments that support or discard the notion
      of discontinuity in correlates of depression. METHODS: Subjects were 183
      depressed elderly persons from the general population, general practitioners and
      mental health care outpatient clinics, and a random elderly control group (n=74).
      Depression was subdivided into symptomatic (n=45), DSM-IV minor (n=73), and DSM
      IV major (n=65) depression. The groups were compared with respect to a variety of
      variables from different domains. RESULTS: Most variables showed a marked
      difference between the control group and the depressive groups, and smaller or no
      differences between depressive subtypes. LIMITATIONS: The data were collected
      cross-sectionally. CONCLUSIONS: With a few notable exceptions, all subtypes of
      depression were significantly different from the control group, while differences
      between depressive subtypes were generally smaller. Depressive subtypes showed no
      discontinuum with respect to the associated variables. Similar associations in
      different subtypes of depression may indicate common vulnerability factors.

PMID- 10967366
TI  - Paternal and maternal depressed mood during the transition to parenthood.
AB  - BACKGROUND: The course of postnatal depression was examined in first-time mothers
      and fathers with emphasis on the role of personality and parental relationships
      as risk factors. METHOD: 157 couples were assessed at four points: antenatally
      and at 6, 12 and 52 weeks postnatally. Various measures of mood and personality
      were administered at each of these assessment points. RESULTS: Examination of the
      factors associated with depressed mood suggested that a woman's relationship with
      her own mother was important in the early postpartum stage, and also her level of
      interpersonal sensitivity and neuroticism. For the father, his relationship with
      either his mother or father and his level of neuroticism were associated with his
      mood level early on. By the end of the first year couple morbidity increased,
      with rates of distress being at their highest for both parents, and factors
      associated with depressed mood being linked to partner relationship variables, at
      least for mothers. At most time points, antenatal mood and partner relationship
      were significant predictor variables for the postnatal mood of both mothers and
      fathers. LIMITATIONS: The sample had a relatively high level of education and
      this should be taken into account when considering the generalisation of findings
      to less educated populations. At the time of conducting this study, the Edinburgh
      Postnatal Depression Scale (EPDS) had only been validated for use in the first
      few months postpartum, and thus we used another scale to measure the mother's
      mood at the other assessment points (the Beck Depression Inventory). Current
      research would suggest that the EPDS is valid both antenatally and at other times
      in the first year postpartum. CONCLUSION: Whilst there was some consistency for
      mothers and fathers in the variables that predict their postpartum adjustment,
      these being antenatal mood and partner relationship, there is also evidence that
      adjustment to parenthood was related to different variables at different times.
      Early adjustment was related to the couple's relationship with their own parents,
      as well as their own personality. Later adjustment was related to the couple's
      functioning and relationship.

PMID- 10967368
TI  - Deliberate self poisoning with antidepressant drugs: a comparison of the relative
      hospital costs of cases of overdose of tricyclics with those of selective
      serotonin re-uptake inhibitors.
AB  - BACKGROUND: Debate continues over the relative merits of tricyclics and selective
      serotonin re-uptake inhibitors (SSRIs) as first line antidepressant treatment for
      depression. SSRIs are safer in overdose but more expensive than tricyclics. This
      report compared the hospital costs of cases of overdose with both groups of drug.
      METHODS: Records of all persons aged over thirteen years presenting to a general
      hospital in one year were analysed for demographic information and details of
      their attendance. RESULTS: There were 1165 episodes of self-poisoning, 151
      involving tricyclics as the sole antidepressant and 69 SSRIs as the sole
      antidepressant. Those taking SSRIs had a shorter (1.96 vs. 2.59 days) and less
      expensive ( pound330 vs. pound567) stay. A large proportion of this difference in
      cost was due to a small number of admissions to the Intensive Care Unit.
      LIMITATIONS: This study used only hospital costs, so excluding costs associated
      with primary care. CONCLUSIONS AND CLINICAL RELEVANCE: If there were similar cost
      differences countrywide, the difference in hospital costs of self poisoning with
      SSRIs and tricyclics would represent an additional pound3.87 million per year due
      to self poisoning with tricyclics across the whole of England and Wales. This is
      a small proportion of the estimated pound100 million cost of switching to first
      line prescribing of SSRIs for depression.

PMID- 10967369
TI  - A prospective follow-up study of ECT outcome in older depressed patients.
AB  - BACKGROUND: This study examined the relationship between age and outcome of
      electroconvulsive therapy (ECT). METHOD: This was a naturalistic, prospective
      follow-up of 81 consecutive in-patients with primary major depression. ECT
      outcome was compared for three age groups - under 65, 65-74 and 75 years and over
      - on the Hamilton Rating Scale for Depression (HRSD), Global Assessment of
      Functioning scale (GAF) and clinical outcome rating scale. Assessments were
      performed pre-ECT, immediately post-ECT, 1-3 years later and, for patients
      suspected of having dementia, 5 years later. RESULTS: At post-ECT and follow-up,
      improvement on HRSD and clinical outcome ratings were comparable for patients in
      the three age groups. Improvements on GAF were also comparable post-ECT, but not
      between post-ECT and follow-up. At follow-up, 35.7% of the oldest group had
      dementia. Importantly, patients who did and did not develop dementia were
      clinically indistinguishable prior to ECT. The number and severity of common
      adverse events were similar pre- and post-ECT and were not associated with age.
      CONCLUSIONS: Depressive outcome and adverse effects of ECT are largely
      independent of age. Older patients receiving ECT appear to have a higher risk of
      developing dementia, possibly underpinned by cerebrovascular disease.

PMID- 10967370
TI  - The long-term outcome of a depressive population in a Hungarian material.
AB  - The authors made a follow-up study among 118 depressive patients. The follow-up
      period was 11 years (mean 7.8 years). They have used the operational criteria
      elaborated by Lee and Murray. The suicide rate was 2.54%, calculated for annual
      average per 100000 inhabitants is 231.5. This figure is close to ten times higher
      (9.7) than the annual suicide rate of the general population of the district from
      the patients who were admitted (23.8). They found 'very good outcome' 25.4%,
      'moderate outcome not readmitted' 42.4%, 'moderate outcome readmitted' 13.6% and
      'very poor outcome' 13.6%. They summarised the available literature.

PMID- 10967372
TI  - Trinucleotide repeat expansion in the beta1 subunit of the sodium pump in manic
      depression illness: a negative study.
AB  - BACKGROUND: Trinucleotide repeats have become a recognized molecular abnormality
      in a variety of neuropsychiatric conditions. Bipolar illness has been purported
      to be a possible trinucleotide repeat-associated disease. Since abnormalities in
      the expression and regulation of the sodium- and potassium-activated adenosine
      triphosphatase (Na,K-ATPase) have been documented in bipolar patients and since
      the beta1 subunit of this pump contains a heterogenous GCC repeat, we decided to
      investigate the possibility of a repeat expansion in beta1 subunit of Na,K-ATPase
      in bipolar patients. METHODS: DNA from postmortem temporal cerebral cortex tissue
      of five bipolar subjects and five matched normal controls and five
      lyumphoblastoid cells lines from the Old Order Amish bipolar pedigrees and match
      normal controls were used for this study. The GCC rich region of beta1 DNA was
      amplified by polymerase chain reaction (PCR) and sequenced. RESULTS: The range of
      GCC repeat in the beta1 gene is between 7 and 9 in our population. This is not
      different in bipolar patients from normal controls. LIMITATIONS: This study
      examined a small number of patients and examined a very limited portion of the
      locus. CONCLUSION: It appears that there is not an expansion of the GCC repeat in
      the beta1 gene in bipolar patients.

PMID- 10967371
TI  - Enhancement of the antidepressant action of fluoxetine by folic acid: a
      randomised, placebo controlled trial.
AB  - BACKGROUND: A consistent finding in major depression has been a low plasma and
      red cell folate which has also been linked to poor response to antidepressants.
      The present investigation was designed to investigate whether the co
      administration of folic acid would enhance the antidepressant action of
      fluoxetine. METHODS: 127 patients were randomly assigned to receive either 500
      microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine
      daily. All patients met the DSM-III-R criteria for major depression and had a
      baseline Hamilton Rating Scale (17 item version) score for depression of 20 or
      more. Baseline and 10-week estimations of plasma folate and homocysteine were
      carried out. RESULTS: Patients receiving folate showed a significant increase in
      plasma folate. This was less in men than in women. Plasma homocysteine was
      significantly decreased in women by 20.6%, but there was no significant change in
      men. Overall there was a significantly greater improvement in the fluoxetine plus
      folic acid group. This was confined to women where the mean Hamilton Rating Scale
      score on completion was 6.8 (S.D. 4. 1) in the fluoxetine plus folate group, as
      compared to 11.7 (S.D. 6. 7) in the fluoxetine plus placebo group (P<0.001).A
      percentage of 93. 9 of women, who received the folic acid supplement, showed a
      good response (>50% reduction in score) as compared to 61.1% of women who
      received placebo supplement (P<0.005). Eight (12.9%) patients in the fluoxetine
      plus folic acid group reported symptoms possibly or probably related to
      medication, whereas in the fluoxetine plus placebo group 19 (29.7%) patients
      reported such symptoms (P<0.05). LIMITATIONS AND CONCLUSIONS: Folic acid is a
      simple method of greatly improving the antidepressant action of fluoxetine and
      probably other antidepressants. Folic acid should be given in doses sufficient to
      decrease plasma homocysteine. Men require a higher dose of folic acid to achieve
      this than women, but more work is required to ascertain the optimum dose of folic
      acid.

PMID- 10967374
TI  - Special communication

PMID- 10967373
TI  - Moderate and severe depression. Gradations for the Montgomery-Asberg Depression
      Rating Scale.
AB  - BACKGROUND: Despite its importance, no distinction between moderate and severe
      depression using the Montgomery-Asberg Depression Rating Scale (MADRS) based on a
      direct comparison with the Hamilton Depression Rating Scale (HAMD-17) is
      available. METHODS: HAMD-17 and MADRS ratings from N=40 at least moderately
      depressed inpatients with major depression (DSM-III-R) were analyzed. Linear and
      non-parametric correlations were computed and a MADRS cut-off score for severe
      depression using an HAMD-17 score of at least 28 points as reference was
      estimated. RESULTS: HAMD-17 and MADRS mean scores were 24.6+/-4.3 and 32.6+/-5.0
      points, respectively. Linear correlation of both scores was r=0.70 (P<0.0005). A
      MADRS cut-off score of at least 35 points was estimated to separate 'moderate'
      from 'severe' depression corresponding to a HAMD-17 cut-off of 28 points with
      sufficient sensitivity and specificity. LIMITATIONS: The sample size was limited
      and no observer ratings directly assessing the severity of depression were used.
      CONCLUSIONS: The preliminary findings are in line with previous findings and
      suggest a cut-off score of 35 points to separate moderate from severe depression
      with the MADRS accepting an HAMD-17 score of >/=28 point as reference. Further
      studies on this issue are warranted.

PMID- 10967375
TI  - The case to fund universal newborn hearing screening in New York State.

PMID- 10967376
TI  - Linguistic development in cleft palate patients with and without compensatory
      articulation disorder.
AB  - INTRODUCTION: Cleft palate patients frequently show compensatory articulation
      disorder (CAD). CAD severely affects speech intelligibility and requires a
      prolonged period of speech intervention. CAD has been considered a phonologic
      disorder. Thus, it seems necessary to explore the relationship between CAD and
      language development. OBJECTIVE: To study the relationship between language
      development and the presence of CAD in cleft palate patients. MATERIALS AND
      METHODS: Cleft palate children with residual velopharyngeal insufficiency (VPI)
      after palatal closure, with and without CAD were studied. Only patients with an
      age ranging from 3 to 8 years were included in the study group. Twenty-nine cleft
      palate patients with residual VPI and CAD were included in the first group
      (active). The second group was assembled with 29 cleft palate patients with
      residual VPI without CAD, matched by age and sex (control). For evaluating
      language development, all patients were analyzed using the Situational-Discourse
      Semantic (SDS) Model [13]. This Model is a valuable tool for conducting
      naturalistic observation and descriptive assessment of language development. The
      SDS Model provides a detailed description of three contexts (situational,
      discourse, and semantic) in ten levels of cognitive and linguistic organization.
      RESULTS: In all contexts considered by the model of cognitive and linguistic
      organization used for this study, i.e. SDS, a Fischer exact test demonstrated
      that patients with CAD showed a significantly higher frequency of language delay
      as compared with patients without CAD. None of the patients present with CAD
      showed an adequate level of language development. The degree of language delay
      was greater in the situational context as compared to the semantic and discourse
      contexts. CONCLUSIONS: Cleft palate patients present with CAD, demonstrated a
      significantly higher frequency of delay in language development as compared with
      cleft palate patients present with VPI without CAD. From the results of this
      paper, it seems that a detailed evaluation of all aspects of cognitive and
      linguistic organization should be performed in cleft palate patients, especially
      in patients present with CAD. Moreover, it seems that speech intervention in
      cleft palate patients with CAD should address not only the articulation process,
      but also specific aspects of language development.

PMID- 10967377
TI  - Topical use of mitomycin C in laser myringotomy: an experimental study in rats.
AB  - OBJECTIVE: Ventilation tubes are used to a large extent for the treatment of
      otitis media with effusion. As this has some drawbacks, laser myringotomy was
      suggested as a treatment alternative. The use of laser has some advantages but
      its use is limited in prolonging the patency rate of myringotomy. Mitomycin C
      (MMC) is being used in some surgical applications to reduce stenosis as it has
      the property to inhibite activity of fibroblasts. We explored the use of
      mitomycin C as an adjunct in prolonging the patency rate in laser myringotomy on
      rats. METHODS: We performed laser myringotomy on both ears of 20 rats. We, then
      applied MMC with a concentration of 2 mg/ml on 10 rats to one of their ears
      (Group 1). In group 2 we used MMC with a concentration of 1 mg/ml. After a follow
      up of 8 weeks we calculated the patency rate for the two groups and the total
      ears with MMC and without MMC. RESULTS: The mean patency rate observed for group
      1 was found to be 6 weeks whereas for group 2, it was 5.8 weeks. The overall
      patency rate for the ears with and without MMC is 5.9 and 1.5 weeks,
      respectively. While there was a statistical difference between ears with and
      without MMC (P<0.01), there was no difference between the two groups according to
      concentrations. CONCLUSION: Mitomycin C has an adjunct effect in laser
      myringotomy in prolonging the patency rate of myringotomy on rats. Low
      concentrations of mitomycin C have the same effect in this issue.

PMID- 10967378
TI  - Otorhinolaryngological manifestations in children with human immunodeficiency
      virus infection.
AB  - The otorhinolaryngological manifestations (ENTM) in AIDS were first described in
      1983. Continuing research confirmed that the ENTM reached up to 100% of the
      infected individuals. In the infant population, this percentage is also found,
      differing by presenting specific ENTM. The main objectives of this study were to
      define the most common ENTM in HIV children and to observe the difference, when
      compared to non-infected children. The HIV detection was also correlated with the
      appearance of the first ENTM. The observational, case-control research involved
      the study of 40 children over a period of 1 year. It was found that HIV children
      have a higher occurrence of ENTM, herpes simplex virus gingivostomatitis,
      cervical lymphadenopathy and parotid hypertrophy. On the other hand, the
      proportion of children who developed rhinosinusitis, acute otitis media (AOM) and
      oral candidiasis (OC) were not statistically different among the groups. However,
      90% of the HIV children presented at least one ENTM, as opposed to 45% of the
      immunocompetent children. Differences in the occurrence of the ENTM were noticed,
      some more suggestive of the HIV infection. Furthermore, the majority of the
      infected children had their first ENTM diagnosed before the infection of HIV was
      established.

PMID- 10967379
TI  - Velopharyngeal insufficiency and articulation impairment in velo-cardio-facial
      syndrome: the influence of adenoids on phonemic development.
AB  - Velo-cardio-facial syndrome is the most common contiguous gene disorder in humans
      and constitutes 8% of patients with clefts of the secondary palate. Speech
      disorders, including severe hypernasality and articulation impairment have been
      documented as among the most common clinical manifestations of the disorder. A
      series of 36 consecutive patients with VCFS ranging in age from 3 to 14 years,
      all confirmed to have a 22q11.2 deletion, were studied to determine specific risk
      factors associated with VPI and articulation impairment. Factors studied included
      palatal clefting, hypotonia, platybasia, and adenoid size. The factor that
      correlated most strongly with speech disorders was adenoid hypoplasia or absence,
      a common manifestation in the syndrome. It is hypothesized that early
      identification of the absence or hypoplasia of the adenoids can result in the
      implementation of appropriate therapy plans to avoid severe disorders of speech
      intelligibility.

PMID- 10967380
TI  - Intractable pediatric chronic sinusitis with antrochoanal polyp.
AB  - It has been reported that pediatric chronic sinusitis with antrochoanal polyp is
      difficult to cure because it tends to recur easily even with surgery. Therefore,
      in order to improve its cure rate, aggressive treatment combining polypectomy,
      intra-maxillary intubation through the inferior meatus, macrolide administration,
      etc., was attempted. Thirty-seven sides of pediatric chronic sinusitis with
      antrochoanal polyp and 44 sides of chronic sinusitis without polyp were evaluated
      after the same treatments. The mean age of patients was 9.7 years, and the mean
      intubation period was 20 months. Since subjective improvements in children are
      questionable, the efficacy was evaluated strictly on the basis of X-ray alone
      focusing on the maxillary sinus. Twenty-four percent of the group with
      antrochoanal polyp showed 'excellent' effect, i.e. almost complete resolution of
      the sinus findings, while 45% of the group without polyp showed 'excellent'
      effect, with a mean follow-up period of 3 years and 6 months. This difference was
      significant (P<0. 01, chi(2)-test). These results further document the
      intractableness of chronic sinusitis with choanal polyp in children.

PMID- 10967381
TI  - Vestibular neuronitis in children: study of medium and long term follow-up.

PMID- 10967382
TI  - Ankyloglossia: controversies in management.
AB  - PURPOSE: To determine current beliefs regarding ankyloglossia and its treatment.
      DESIGN: Anonymous written survey. PARTICIPANTS: Otolaryngologists (OTO, n=423),
      pediatricians (PD, n=425), speech pathologists (SP, n=400), and lactation
      consultants (LC, n=350) were randomly selected from professional membership
      lists, with a response rate of 209 (49%), 235 (55%), 150 (37.5%), and 203 (58%),
      respectively. CLINICAL FINDINGS: Sixty-nine percent of LCs, but a minority of
      physician respondents, believe tongue-tie is frequently associated with feeding
      problems. Sixty percent of OTOs, 50% of SPs, but only 23% of PDs believe tongue
      tie is at least sometimes associated with speech difficulties. Sixty-seven
      percent of OTOs versus 21% of PDs believe tongue-tie is at least sometimes
      associated with social/mechanical issues. Surgery is recommended at least
      sometimes for feeding, speech, and social/mechanical issues by 53, 74, and 69% of
      OTOs, respectively, but by only 21%, 29%, and 19% of PDs. CONCLUSION: The
      significance of ankyloglossia in children remains controversial, both within, and
      between, specialty groups.

PMID- 10967383
TI  - Cricotracheal resection as a primary procedure for laryngotracheal stenosis in
      children.
AB  - OBJECTIVE: Cricotracheal resection (CTR) is being increasingly used in the
      treatment of children with severe laryngotracheal stenosis. In this institution
      the majority of children are treated with CTR as a salvage procedure having
      undergone previous unsuccessful laryngotracheal reconstruction (LTR). Selected
      children have undergone CTR as a primary procedure (without previous LTR). The
      objective of this study is to examine the outcome for children undergoing
      cricotracheal resection as a primary procedure for severe laryngotracheal
      stenosis. METHOD: analysis from prospectively collected database. RESULTS: 17
      patients underwent CTR without previous LTR or anterior cricoid split between
      October 1994 and September 1998. All the patients had grade 3 or 4 stenosis.
      After a minimum of 1 year follow up 15 children are decannulated. Five children
      required further surgery to achieve this. Two children still have tracheostomies.
      Both had extended procedures. One included bilateral arytenoid abduction for
      bilateral vocal cord paralysis in a patient with quadraparesis following
      transverse myelitis. The other child, who suffered from multiple congenital
      anomalies, underwent a concurrent posterior cricoid cartilage graft. Nine
      patients had good voice post-operatively, five had acceptable voice and three had
      weak or no voice. CONCLUSION: the early experience for CTR in children as a
      primary procedure achieved an overall decannulation rate of 88% after 1 year
      follow up in children with severe laryngotracheal stenosis. Five children
      required further surgery to achieve this. The voice outcome was variable. CTR is
      an alternative primary procedure to LTR for severe laryngotracheal stenosis in
      children. The relative indications for these procedures are discussed.

PMID- 10967384
TI  - Tracheal stenosis and congenital heart disease in patients with Down syndrome:
      diagnostic approach and surgical options.
AB  - Upper airway obstruction is a prevalent feature in patients with Down syndrome.
      However, these patients may be completely asymptomatic in the early months of
      life. The recognition of a problem within the airway quite often occurs when
      these children present for cardiac surgery, diagnostic radiography with sedation,
      or during the induction and intubation for anesthesia. Tracheal stenosis is rare
      in the general population, but is seen somewhat more frequently in patients with
      Down syndrome. The incidence of tracheal stenosis in children with congenital
      heart disease, which is seen in 40% of patients with Down syndrome, has been
      reported to be 1.2%. Patients with Down syndrome also tend to have other upper
      airway obstructive pathology such as nasopharyngeal, oropharyngeal, and
      subglottic compromise. These entities, combined with the high incidence of
      cardiac disease, put these children at risk for acute and chronic cardiopulmonary
      compromise. We present two patients with Down syndrome and congenital heart
      disease who were found to have significant tracheal stenosis at the time of their
      cardiac surgery. The perioperative management of their airway defects including
      diagnostic evaluation and treatment modalities are discussed.

PMID- 10967385
TI  - Rate of persistent perforation after elective tympanostomy tube removal in
      pediatric patients.
AB  - This study was performed to determine the rate of persistent perforations
      according to age, tube type and duration of intubation in children who underwent
      elective tympanostomy tube removal. Our retrospective analysis of hospital and
      clinic charts included all patients who underwent elective tube removal from July
      1995 to December 1997 at our institution. Information from the chart review
      included patient age at time of tube removal, type of tube removed, duration of
      intubation, presence of granulation tissue/polyps, and concomitant paper patch
      placement. The outcome of each surgical removal was determined by examining
      follow-up clinic charts. A patient was deemed to have a persistent perforation if
      the eardrum had not adequately healed within 3 months after surgery. Data on 201
      patients were gathered. These patients had 273 tube removals. Eleven percent of
      ears (29/273) had persistent perforations. According to tube type, no
      perforations (0/48) occurred with Collar Bobbin tubes, 6% (3/50) with Tytan
      tubes, 7% (3/44) with Duravent tubes, and 22% (16/74) with Paparella II tubes.
      Three percent (3/101) of tubes in place for <3 years and 15% (26/172) of tubes in
      place for >3 years showed persistent perforations after removal. Ears with
      granulation polyps had a 9% (18/203) rate of perforations, whereas those without
      granulation polyps had a 16% (11/70) rate of perforations. Forty percent (4/10)
      of ears were treated with paper patches at the time of tube removal showed
      persistent perforations. Our data indicate that the rate of persistent
      perforation (11%) after elective tympanostomy tube removal is high. The factors
      associated with higher rates of persistent perforation (P<0.05) include duration
      of intubation >3 years prior to removal and the use of long-term Paparella II
      tubes.

PMID- 10967386
TI  - Case report: an unusal cause of stridor in a post-liver transplant 6-year old.
AB  - Polymorphic lymphoproliferative disorder is a recognised cause of upper airway
      obstruction in children [N. Sculerati, M. Arriga, Ann. Otol. Rhinol. Laryngol 99
      (1990) 445-450]. It is associated with long-term immunosuppression therapy and
      frequently with Epstein-Barr virus (EBV) infection [D.W. Hanto, Annu. Rev. Med.
      46 (1995) 381-394; B.D. Fletcher, H.E. Heslop, H.C. Kaste, S. Bodner, Upper
      airway obstruction and pulmonary abnormalities due to lymphoproliferative disease
      following bone marrow transplantation in children, Pediatr. Radiol. 28 (1998) 492
      496]. The prevalence in reported series ranges from 4 to 13% among post
      transplant children [M. Ho, R. Jaffe, G. Miller, Transplantation 45 (1988) 719
      727; G.B. Hammer, S. Cao, M.G. Boltz, A. Messner, Anesthesiology 89 (1998) 263
      265; B.V. Lattyak, P. Rosenthal, Post-transplant lymphoproliferative disorder
      presenting in the head and neck, Laryngoscope 108 (1998) 1195-1198]. This
      condition may present in the transplanted allograft, the gastrointestinal tract,
      the head and neck, and in particular in the upper airway. Previously reported
      cases of upper airway obstruction have been in the supraglottis, Waldeyer's ring,
      the glottis, and one case of an intra tracheal mass [M. Ho, R. Jaffe, G. Miller,
      Transplantation 45 (1988) 719-727; G.B. Hammer, S. Cao, M.G. Boltz, A. Messner,
      Anesthesiology 89 (1998) 263-265]. We report a case of post-transplant
      lymphoproliferative disorder in the sub-glottis causing acute upper airway
      obstruction with negative (EBV) serology.

PMID- 10967387
TI  - Anterior submucous laryngeal cleft.
AB  - Upper airway obstruction in the newborn is frequently due to congenital laryngeal
      anomalies. One of these, the posterior laryngeal cleft, is often associated with
      subglottic stenosis and respiratory difficulty. This discussion of the anterior
      laryngeal cleft reports findings in an infant who required intubation immediately
      after birth and survived only 3 days. The anterior cricoid cleft was associated
      with severe congenital anomalies including congenital tracheal stenosis.

PMID- 10967388
TI  - Ossifying fibroma arising in the right ethmoid sinus and nasal cavity.
AB  - Ossifying fibroma, a rare tumor entity, is a well-demarcated benign fibro-osseous
      tumor composed of bone, fibrous tissue and cementum. It is commonly found in the
      mandible, but also found in the maxilla and paranasal sinuses. Simple curettage
      is enough when the fibrous lesions are located in the mandible but a complete en
      bloc excision is required when these lesions are located in the maxilla and
      paransal sinuses to relieve symptoms and prevent recurrence. With the advent of
      sinonasal endoscopy in the mid 1980s, and subsequent advances in surgical
      techniques, endoscopic management of the fibrous-osseous lesions has become
      possible. In the current case study, we report a successful endoscopic removal of
      a huge ossifying fibroma located in the right ethmoid sinus and nasal cavity.

PMID- 10967389
TI  - Antrochoanal polyp presenting with obstructive sleep apnoea and cachexia.
AB  - A rare presentation of an antrochoanal polyp is reported. A 14-year-old boy
      presented with obstructive sleep apnoea and subnormal growth velocity for height
      and weight over a 1-year period. Examination revealed a post-nasal mass which
      following removal was confirmed histopathologically as an antrochoanal polyp.
      Relief of the airway obstruction was promptly followed by catch-up growth and
      subsequent normal growth velocities. The possible mechanisms underlying the
      cachexia are explored including the possible association with the obstructive
      sleep apnoea.

PMID- 10967390
TI  - Third branchial cleft anomaly presenting as a retropharyngeal abscess.
AB  - Branchial cleft anomalies are congenital developmental defects that typically
      present as a soft fluctuant mass or fistulous tract along the anterior border of
      the sternocleidomastoid muscle. However, branchial anomalies can manifest
      atypically, presenting diagnostic and therapeutic challenges. Error or delay in
      diagnosis can lead to complications, recurrences, and even life-threatening
      emergencies. We describe a case of an infected branchial cleft cyst that
      progressed to a retropharyngeal abscess in a 5-week-old female patient. The
      clinical, radiographic, and histologic findings of this rare presentation of
      branchial cleft cyst are discussed.

PMID- 10967391
TI  - Syndrome of recurrent meninigitis due to congenital perilymph fistula with two
      different clinical presentations.
AB  - Recurrent meningitis secondary to a congenital labyrinthine anomaly is a rare
      clinical entity, diagnosis of which is dependent upon certain clinical,
      radiological and intraoperative features. In the following report we describe two
      children with congenital labyrinthine fistula and recurrent meningitis whose
      clinical presentation, radiological features and intraoperative findings were
      dissimilar and thus, illustrative of two different ways of presentation of this
      rare disorder. While one had a classical Mondini defect and unilateral hearing
      loss, the other had normal audiometric and radiographic findings. The fistulae
      were successfully closed via a tympanotomy approach in both the patients.

PMID- 10967392
TI  - Pathologic alterations in adult rainbow trout, Oncorhynchus mykiss, exposed to
      dietary 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Adult female rainbow trout (Oncorhynchus mykiss) fed [3H]2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) impregnated diet at 0, 1.8, 18 or 90 ng/kg
      food for up to 320 days were evaluated by clinical pathology, gross pathology and
      histopathology procedures. Gross pathological changes were limited to a slight
      increase in the incidence of lesions of the caudal fins in the treated groups.
      Mixed mononuclear inflammatory infiltrates were present in multiple organs of
      fish from control and treatment groups, but did not appear to be treatment
      related. Lesions associated with exposure to TCDD were observed histologically in
      liver and spleen after 100 and 250+ days of exposure. The livers of TCDD-treated
      fish contained less hepatocellular glycogen, more mitotic figures, greater
      anisokaryosis, anisocytosis, nuclear chromatin clumping and margination.
      Prominent nucleoli were directly proportional to TCDD dose. Hepatocellular
      changes in fish exposed to TCDD also included single cell necrosis and clear
      cytoplasmic vacuoles consistent with lipid. Some fish from all TCD exposed groups
      had lower lymphoid density compared to controls at all time intervals. Fish
      exposed to the highest TCDD dose had decreased peripheral leukocyte counts after
      50 and 100 days. The lowest observable adverse effect level (LOAEL) for these
      effects was 5.69 ngTCDD/kg in diet and 0.90 ng TCDD/kg liver.

PMID- 10967393
TI  - Metal accumulation and metallothionein in two populations of brown trout, Salmo
      trutta, exposed to different natural water environments during a run-off episode.
AB  - Cd, Cu and Zn concentrations were measured in ambient water as well as in gills,
      liver and kidney tissues of two natural populations of brown trout (Salmo trutta)
      during a run-off episode in two rivers with different metal compositions due to
      mining pollution. Metallothionein (MT) was also measured in these tissues. The
      two rivers, Rugla (Cu contaminated) and Naustebekken (Cd and Zn contaminated),
      are located in two neighboring drainage basins separated by the topographic
      divide near the city of Roros in the County of Sor-Trondelag, Norway. In Rugla,
      the Cu concentration increased from 15 ug/l at the low water level to 41 ug/l
      during the run-off episode. In Naustebekken, corresponding values for Cd were 90
      170 ng/l and those for Zn were 49-91 ug/l. Gill concentrations of Cu and Cd/Zn MT
      in both populations of native trout clearly reflect the presence of these metals
      in the rivers during the run-off, in accordance with the hypothesis of protection
      caused by MT induction. When Rugla trout were transferred to Naustebekken and
      vice versa, both the amounts of MT itself and the Cu contents reflected the
      concentration of this metal in the new environment, indicating that MT induction
      also protects against acutely increased metal levels. The measured levels of MT
      in both native and transferred trout can account for all the Cd present in the
      tissues, but not for all of the Cu and Zn. The capacity of MT to regulate Cd and
      Cu in the trout populations in their natural habitat therefore seems clearly
      present. Our data also indicate that the MT I and II isoforms may bind metals
      selectively.

PMID- 10967394
TI  - Interrelationship of apoptosis, mutation, and cell proliferation in N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG)-induced medaka carcinogenesis model.
AB  - The present study examined the interrelationship of GSH depletion, apoptosis,
      mutation, and cell proliferation following carcinogen exposure. Medaka (Oryzias
      latipes) were investigated following a 28 day, three times/week pulse exposure to
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Fish (5 weeks old) were exposed to
      MNNG at concentrations of 0, 0.5, and 1 mg l(-1) and reared for 3, 5 and 7 more
      months after the last day of exposure. GSH levels were decreased in the higher
      concentration groups and longer-reared groups. Flow cytometric analysis revealed
      that fish from the groups reared 3 and 5 months showed active apoptotic changes
      in the dose- and time-dependent manner, but the group reared 7 months had fewer
      apoptotic, rather showed more necrotic and carcinogenic alterations. Mutational
      responses were detected by an arbitrarily primed polymerase chain reaction (AP
      PCR) fingerprinting method using whole body DNA samples as templates and pBR
      primer. A mutational change was expressed by a loss or gain of a band. There was
      a time-dependent mutational change, but no distinctive concentration-dependent
      one. A band from normal fish sample that disappeared after treatment of MNNG was
      excised and sequenced. The band had an 869 base pair-long sequence, however,
      there was no putative protein-coding region based on an analysis by DNAsis.
      Spindle cell sarcomas invading muscle were detected on the whole body sections
      from three of ten fish examined, and immunohistochemical analysis with PCNA
      showed that tumor cells were actively proliferating. However, terminal
      deoxynucleotidyl transferase (TdT) assay showed that tumored fish still had
      active apoptotic cell changes in the tissues without tumor. This study shows not
      only the interrelationship of GSH depletion, apoptosis, mutation and cell
      proliferation, but also indicates that medaka is appropriate as a fish model for
      research on the passage of carcinogenesis.

PMID- 10967395
TI  - Histopathology of the hepatopancreas and gills of the prawn Macrobrachium
      malcolmsonii exposed to endosulfan.
AB  - The tissue damage induced by various organic pollutants in aquatic animals is
      well-documented, but there is a dearth of information relating to the
      histological alterations induced by pesticides in freshwater prawns of the genus
      Macrobrachium. In the present study intermoult juveniles of the freshwater prawn
      Macrobrachium malcolmsonii (total length, 4.5-5.0 cm; weight, 1.0-1.25 g) were
      exposed to three sublethal concentrations of the organochlorine pesticide,
      endosulfan (10.6, 16.0 and 32.0 ng/l) for a period of 21 days. The hepatopancreas
      and gills of the prawns were then dissected out and processed for light
      microscopic studies. Exposure to endosulfan was found to result in several
      alterations in the histoarchitecture of the hepatopancreas and gills of M.
      malcolmsonii. The alterations included: hemocytic infiltration in the
      interstitial sinuses, thickening of basal laminae and necrosis of the tubules of
      the hepatopancreas; accumulation of hemocytes in the hemocoelic space, swelling
      and fusion of lamellae, abnormal gill tips, hyperplastic, necrotic, and clavate
      globate lamellae of the gills. The results obtained suggest that the
      hepatopancreas and gills of prawns exposed to endosulfan were structurally
      altered. Such alterations-could affect vital physiological functions, such as
      absorption, storage and secretion of the hepatopancreas, and respiration, osmotic
      and ionic regulations of the gills, which in turn could ultimately affect the
      survival and growth of M. malcolmsonii. Thus, all possible remedial measures
      should be adopted to prevent the occurrence of pesticide contamination in the
      aquatic environment.

PMID- 10967396
TI  - Effects of glutathione depletion on copper cytotoxicity in oysters (Crassostrea
      virginica).
AB  - Glutathione is a tripeptide that plays an important role in ameliorating metal
      toxicity. Depletion of glutathione has been associated with an increased risk of
      metal toxicity in mammals. An understanding of the toxicological significance of
      glutathione depletion in oysters would be of considerable importance given the
      widespread use of bivalves in biological monitoring. Laboratory studies were
      conducted by using an inhibitor of glutathione synthesis (buthionine sulfoximine)
      to investigate the effects of glutathione depletion on metallothionein
      expression, lysosomal membrane destabilization, and lipid peroxidation in Cu
      exposed oysters. In oysters exposed to Cu (20 and 80 ug/l) and buthionine
      sulfoximine (20 mg/l), metallothionein induction was suppressed and cellular
      stress responses were frequently higher than those observed in oysters exposed
      singly to Cu. Together, these results suggest that environmental conditions that
      cause glutathione depletion may increase the potential for adverse effects to
      pollutants during in situ exposures.

PMID- 10967397
TI  - Total oxyradical scavenging capacity (TOSC) in polluted and translocated mussels:
      a predictive biomarker of oxidative stress.
AB  - Several classes of environmental pollutants are known to enhance the
      intracellular formation of reactive oxygen species in marine invertebrates with
      different consequences on their antioxidant system. Despite variations in the
      endogenous levels of antioxidants may reveal biological effects induced by
      pollutants, the overall efficiency of antioxidant system is not evaluated from
      such data. The total oxyradical scavenging capacity (TOSC) assay measures the
      biological resistance to various kinds of oxyradicals, thus providing useful
      indications to predict oxyradical-mediated adverse effects on the physiological
      condition of the organisms. In the present work, the capability to neutralize
      three potent cellular oxidants (peroxyl radicals, hydroxyl radicals and
      peroxynitrite) was compared in two natural populations of mussels from a clean
      and a metal polluted area, respectively, and in control organisms translocated
      for 8 weeks to the contaminated site. Within each group of mussels, the relative
      efficiency towards the various forms of oxyradicals, showed peroxyl radicals and
      hydroxyl radicals as the less and the most difficult species, respectively, to
      neutralize by cellular antioxidants. When the two populations were compared,
      polluted organisms revealed a significantly higher susceptibility to oxidative
      stress as indicated by their lower TOSC values. A significant reduction of
      antioxidant capacity was observed also in translocated organisms where only a
      moderate recovery was evident at the longer exposure time. Separation of soluble
      antioxidants from the protein fraction, suggested a greater depletion of low
      molecular weight molecules during the first phase of exposure to pollutants. The
      pollutant-induced impairment of antioxidant capability precludes the appearance
      of oxyradical toxicity. In the present study a high correlation was obtained
      between reduced TOSC values and lower Neutral Red retention time in lysosomal
      compartment of circulating haemocytes. The TOSC towards different forms of
      oxyradicals is confirmed an useful biomarker with predictive validity at the
      organism level.

PMID- 10967398
TI  - 17-alpha-ethinylestradiol affects reproduction, sexual differentiation and
      aromatase gene expression of the medaka (Oryzias latipes).
AB  - Juvenile medaka (Oryzias latipes) of the d-rR strain were exposed for 2 months to
      1, 10 and 100 ng/l of the environmental estrogen 17-alpha-ethinylestradiol
      (EE(2)). The exposure period was followed by a 6 week recovering period in order
      to detect long-lasting effects on sexual differentiation. Survival rate, sex
      ratio, gonadal growth, spawning, fecundity, histology as well as the ovarian gene
      expression of aromatase were monitored. At 100 ng/l EE(2), all XY medaka were sex
      reversed and had developed an ovary. At lower EE(2) concentrations, which did not
      result in sex reversal, no alteration of testicular structure was detected and
      male fertility appeared to be unchanged. In XX females, reduced production of
      eggs was reflected in a significantly reduced gonadal weight at 10 and 100 ng/l
      EE(2). Aromatase, which in gonads is normally only expressed in ovaries, was
      detectable in testis of XY males exposed to 10 ng/l EE(2). The results indicated
      that a combination of different biological endpoints provide a suitable set of
      parameters for the biological evaluation of xenoestrogens, since the expression
      of molecular marker genes was not always paralleled by morphological
      deficiencies.

PMID- 10967399
TI  - Induction of cytochrome P450 1A in the American Eel by model halogenated and non
      halogenated aryl hydrocarbon receptor agonists.
AB  - Eels (Anguilla sp.) have phylogenetic, life history, and morphological
      characteristics which distinguish them from many other species that have been
      examined for cytochrome P450 1A (CYP1A) induction. Members of the family
      Anguillidae often occur in regions of the coastal environment that are heavily
      impacted by chemical contamination. Although eels have been suggested to be a
      useful species for biomonitoring, the sensitivity with which eel CYP1A is induced
      by aryl hydrocarbon receptor (AHR) agonists is not known. We investigated the
      dose-dependent induction of hepatic CYP1A in the American eel (Anguilla
      rostrata). Eels from an uncontaminated site were injected intra-peritoneally with
      the model AHR agonists beta-naphthoflavone (BNF), benzo[a]pyrene (B[a]P) or
      3,3',4,4-tetrachlorobiphenyl (TCB) at increasing doses (BNF at 0.1, 1, 10 and 100
      mg/kg, B[a]P at 0.1, 1 and 10 mg/kg, and TCB at 0.1, 1, 10 and 20 mg/kg). All
      three compounds produced dose-dependent induction of CYP1A content and catalytic
      activity. An estimated ED(50) for induction of liver microsomal EROD activity by
      TCB was approximately 5 mg/kg, indicating only moderate sensitivity. At
      comparable doses of 1 and 10 mg/kg (or 3-4 and 30-40 umol/kg), BNF and B[a]P had
      2-3-fold greater effect than TCB in eliciting hepatic CYP1A induction. Injection
      of radiolabeled B[a]P and TCB resulted in similar dose-dependent concentrations
      of these compounds in eel liver, and the hepatic inducer concentrations and CYP1A
      levels were correlated positively. Eels collected from New Bedford Harbor (NBH),
      a Superfund site highly contaminated by polycyclic aromatic hydrocarbons and
      polychlorinated biphenyls, had levels of microsomal CYP1A protein and EROD
      activity that were equivalent to the highest levels induced experimentally. Eels
      from less contaminated sites had correspondingly less CYP1A expression. The
      responses to B[a]P or BNF as compared to TCB suggest a lower efficacy and/or
      potency for CYP1A induction by TCB which could involve differences in the
      mechanisms of responses to these compounds in eels. However, the moderate
      sensitivity and the CYP1A induction in NBH eels support suggestions that eels may
      be useful in monitoring more contaminated regions.

PMID- 10967400
TI  - Toxicity of TCDD in European flounder (Platichthys flesus) with emphasis on
      histopathology and cytochrome P450 1A induction in several organ systems.
AB  - The present study is part of a series of experiments, set up to elucidate the
      impact of aquatic pollution on fish health in the marine and estuarine
      environment. In the Dutch coastal and estuarine waters, European flounder
      (Platichthys flesus) showed a relatively high prevalence of (pre)neoplastic liver
      lesions and lymphocystis virus disease. The hypothesis of a causal relationship
      between pollution and these diseases was supported by semi-field experiments.
      Therefore a series of laboratory experiments was performed to further
      substantiate causality and identify the xenobiotics that may play a major role in
      the field. Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)
      are important environmental pollutants. They are highly persistent, highly
      lipophilic, and have shown to induce several toxic effects in mammalian and non
      mammalian species at relatively low concentrations. This report describes a study
      in which European flounder were orally exposed to the most toxic PCDD congener,
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or to harbor sludge extract under
      controlled laboratory conditions. The effects on several organs (liver, gills,
      gastro-intestinal tract, thyroid gland, gonads, spleen and mesonephros) were
      examined microscopically. Induction and localization of cytochrome P4501A (CYP1A)
      immunoreactivity, and effects on hepatocyte-proliferation were visualized
      immunohistochemically. Effects on thymus size were examined by morphometric
      analysis. Oral exposure of flounder to 0.0125 or 0.3125 ug TCDD/kg bw, or to
      0.3125 ug TEQ/kg bw of a harbor sludge extract, weekly for 8 weeks, induced a
      significant increase in CYP1A immunoreactivity in hepatocytes. Single
      administration of higher doses (20, 100 and 500 ug/kg bw) of TCDD also induced a
      significant increase CYP1A immunoreactivity in the endothelium in all organs
      examined, and in the epithelium of the digestive tract, liver, and mesonephros.
      Remarkably, strong immunoreactivity was noted in a distinct cell population of
      the hematopoietic tissue in the mesonephros and spleen, which has not been
      described in fish previously. Moreover, oral exposure to 20 ugTCDD/kg bw resulted
      in an increased mitotic activity, and an increased hepatosomatic index was found
      after exposure to 500 ugTCDD/kg bw. In the thymus only a trend in size reduction
      was noted, again in the highest dose group. Nevertheless, no marked pathology was
      detected even in fish exposed to a single dose of 500 ug TCDD/kg body weight. The
      present experiments show that, under the actual experimental conditions, European
      flounder is relatively insensitive to the toxic effects of TCDD. However, we
      assume that exposure to TCDD (and related substances) may promote the development
      of tumors in the field.

PMID- 10967401
TI  - Effect of a dioxin-like PCB (CB 126) on the biotransformation and genotoxicity of
      benzo
AB  - Two experiments were performed to study the interaction between benzo[a]pyrene
      (BaP) and the planar, dioxin-like PCB congener 3,3',4,4',5-pentachlorobiphenyl
      (CB 126) in the flatfish dab (Limanda limanda). The first experiment involved
      four groups. Group I was treated with 10 ug/kg CB 126, group II was treated with
      2 mg/kg BaP, group III was first treated with 10 ug/kg CB 126 and exposed to 2
      mg/kg BaP 6 days later, and group IV was a control group. The second experiment
      was similar, except that the BaP dosage level was increased to 50 mg/kg. Pre
      treatment with 10 ug/kg of CB 126 always caused the induction of hepatic
      cytochrome P450 1A (CYP1A), as measured by significant increases of the model
      reaction 7-ethoxyresorufin-O-deethylase (EROD) in microsomal preparations.
      Treatment of dab with BaP caused a significant EROD induction at the 50 mg/kg,
      but not at the 2 mg/kg level. Concurrent with EROD induction by either CB 126 or
      50 mg/kg BaP, was a significant change in the biliary metabolite pattern in
      favour of 1-hydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene and towards a lower
      fraction of the procarcinogen BaP-7,8-dihydrodiol (7,8-DIOL). Pre-treatment with
      CB 126 did not cause an increase of hepatic BaP DNA adducts formed after
      treatment with either 2 or 50 mg/kg BaP. Glutathione S-transferase (GST)
      activities remained also unaffected by any of the treatments. The results of this
      study suggest that the pattern of BaP metabolites in bile depends on the level of
      CYP1A induction. Moreover, the concurrence of a potent CYP1A inducer and BaP does
      not necessarily lead to an increase in DNA adduct levels in liver tissue. The
      observation that the level of 7,8-DIOL is decreased despite a higher (CYP1A
      mediated) EROD activity explains, at least in part, the lack of induction of DNA
      adducts.

PMID- 10967402
TI  - Stability of cytochrome P450 proteins in cultured precision-cut rat liver slices.
AB  - The objective of this study was to evaluate the stability of individual,
      xenobiotic-metabolising, cytochrome P450 proteins in precision-cut rat liver
      slices cultured for up to 72 h using the multiwell plate system. This was
      achieved using established diagnostic probes (O-dealkylation of methoxy-, ethoxy-
      and pentoxy-resorufin, testosterone 2alpha-hydroxylase, debrisoquine 4
      hydroxylase, aniline p-hydroxylase and lauric acid hydroxylase) and
      immunologically using Western blotting. All cytochrome P450 activities declined
      in culture, the most rapid loss occurring at about 8-12 h of culture; in all
      cases no detectable activity was present in the 72-h cultured slices. Isoform
      specific differences in the stability of various cytochrome P450 proteins were
      observed, with CYP2E1 being the most stable. When cytochrome P450 expression was
      determined immunologically, a different picture emerged. High levels of
      apoprotein were retained in the slices even when activity was very low. In the
      case of CYP2B, apoprotein levels even increased following the culture of hepatic
      slices. It is concluded, that for tissue slices to become an acceptable in vitro
      alternative system for long-term incubations, the culturing conditions must be
      improved to ensure that cytochrome P450 activities are better maintained.

PMID- 10967403
TI  - A theoretical approach to the mechanism of biological oxidation of
      organophosphorus pesticides.
AB  - Organophosphorus pesticides are the most common classes involved in poisonings
      related to pesticides. We used enzymatic activity of chloroperoxidase on the
      metabolism of some phosphorothioate pesticides published previously and molecular
      mechanics methods to perform a theoretical approach of the mechanism of
      biological oxidation of this class of pesticides. The molecular structure of
      eight pesticides were optimized by molecular mechanics methods using the CAChe
      program package for biomolecules, ver. 3.11 (Oxford Molecular Ltd., Campbell,
      CA). Total energy resulted from the structure optimization process and the
      partial charges of both phosphorus and sulfur were computed for every pesticide.
      Phosphorus partial charge and enzymatic activity were significantly related by
      linear regression analysis (r=0.82, P<0.05). Analyzing our results and using
      previously reported enzymatic activity of chloroperoxidase on these pesticides,
      we deduced chemical events involved in activation of the active site of
      chloroperoxidase and proposed a novel mechanism of oxidation for this class of
      pesticides. This mechanism will also help to understand the oxidation process of
      pesticides by cytochrome P450, and production of toxic metabolites.

PMID- 10967404
TI  - Expression of Fas antigen and apoptosis caused by 5,10,15, 20-tetra(4
      methoxyphenyl)porphyrin (TMP) on carcinoma cells: implication for photodynamic
      therapy.
AB  - The photodynamic effects of 5,10,15, 20-tetra(4-methoxyphenyl)porphyrin (TMP) on
      a Hep-2 cell line were investigated. TMP toxicity in the dark and in relation to
      illumination with visible light was examined. Hep-2 cells were treated with
      different TMP concentrations (1, 5 and 10 microM). The uptake of TMP by Hep-2
      cells increased with TMP concentration and an increase of the initial uptake rate
      was observed with increasing TMP concentrations. However, after 24 h of
      incubation, a similar value of intracellular TMP concentration was reached at all
      three concentrations of TMP added. Cell toxicity induced by TMP was analyzed in
      the dark at different concentrations of the photosensitizer and at several
      incubation periods. The cell mortality obtained after exposure of the cell
      cultures to visible light was exclusively due to the photosensitization effect of
      TMP produced by light irradiation. Staining with the hematoxylin-eosin method
      demonstrated that treatment with TMP, followed by exposure to visible light,
      notably increased the apoptotic figures. Fas antigen was only expressed in these
      conditions. The results contribute to the understanding of the photodynamic
      therapy (PDT) mechanism produced by TMP on Hep-2 carcinoma cell line.

PMID- 10967405
TI  - Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley
      rat.
AB  - Endotoxin (lipopolysaccharide; LPS) and mercury are nephrotoxic compounds of food
      safety concern. Endotoxin is a product of cell walls of gram negative bacteria.
      Humans are constantly exposed to LPS through food, water and air. Food is the
      main source of mercury exposure for humans. Endotoxin potentiates the toxicity of
      a number of xenobiotics, but its interaction with nephrotoxic heavy metals has
      not been investigated. We tested the hypothesis that endotoxin enhances mercury
      induced nephrotoxicity. Thirty-two, 41-43-day-old, male Sprague-Dawley rats were
      allocated randomly to four groups of eight rats each as follows: group I received
      0.9% sodium chloride, group II received 2.0 mg of Escherichia coli 0128:B12 LPS
      kg(-1) once, group III received 0.5 mg mercuric chloride kg(-1) once, and group
      IV received 2.0 mg E. Coli 0128:B12 LPS kg(-1) once 4 h before receiving 0.5 mg
      mercury chloride kg(-1) once. Mercury, LPS and 0.9% sodium chloride were all
      injected IV through the tail vein. Rats were monitored for 48 h after mercury
      injection. Serum creatinine, urea nitrogen, and polyuria were significantly
      increased in rats given LPS plus mercury relative to those given either agent
      alone or saline (P</=0.05). The most severe morphologic lesions were found in
      rats given LPS plus mercury, which also had significantly greater renal mercury
      concentration than those given mercury alone (P < or = 0. 05). In conclusion, LPS
      potentiated mercury-induced nephrotoxicity.

PMID- 10967406
TI  - Hexachlorobenzene-induced alterations on neutral and acidic sphingomyelinases and
      serine palmitoyltransferase activities. A time course study in two strains of
      rats.
AB  - Hexachlorobenzene (HCB) induces porphyria both in humans and rodents, and
      hepatocarcinoma in rodents. In a previous work we observed that HCB produces a
      continuous decrease in hepatic sphingomyelin (SM) content in Wistar rats. A
      distinguishing characteristic of sphingolipids breakdown products is their
      participation in anti-proliferative and apoptotic processes and in the
      suppression of oncogenesis. As a first step to elucidate the role of SM decrease
      in the hepatotoxicity induced by HCB, the present study evaluates the metabolic
      causes of the continuous decrease in hepatic SM content observed in Wistar rats
      with HCB intoxication, and its relation with porphyria development. For this
      purpose, the time-course (3, 7, 15, 21 and 28 days) of the effects of HCB on
      hepatic SM levels and on some of the enzymes of SM synthesis (serine
      palmitoyltransferase, SPT) and catabolism (sphingomyelinases, SMases) was
      followed, using two strains of rats differing in their susceptibility to acquire
      porphyria: Chbb THOM (low) and Wistar (high). HCB (1 g kg(-1) b.w. per day) was
      administered by gastric intubation as an aqueous suspension. After 5 days of HCB
      treatment, animals were allowed a 2-day recovery period without HCB
      administration. Two phases in the HCB-induced damages to sphingolipid metabolism
      were observed. The first stage (7 days of treatment), common to both strains of
      rats, was characterized by a decrease in hepatic SM levels (17-25%) and in SPT
      activity (50-43%), while strain differences were found for the later stage. In
      Chbb THOM rats, hepatic SM content was restored to normal values concomitantly
      with an increase in SPT activity (44%, at day 28), and without any increase in SM
      catabolism. In addition, the level of the other phospholipids was not altered. In
      Wistar rats, hepatic SM levels decreased continuously throughout the experiment,
      accompanied by increases in SPT, acidic sphingomyelinase (A-SMase) and neutral
      sphingomyelinase (N-SMase) activities (86, 28.5 and 78% increase, respectively).
      A role for glutathione (GSH) in the interstrain differences or a direct effect of
      HCB on SM metabolism was not found. The present study: (a) demonstrates that N
      SMase, A-SMase, and SPT are some of the enzymes that play a role in the HCB
      induced decrease of hepatic SM content; (b) finds that HCB-induced alterations of
      SM metabolism do not correlate with HCB-induced accumulation of hepatic
      porphyrins; and (c) proposes a link between HCB-induced alterations in
      phospholipid pattern and in SM metabolism. The increased SM hydrolysis produced
      as a consequence of SMases induction could be regarded as a cellular response to
      liver injury elicited by HCB, perhaps acting through the activation of SM signal
      transduction pathway delaying the proliferative processes observed after long
      term treatment with HCB in some rodent species. However, such protective
      mechanism appears to be strain-dependent.

PMID- 10967408
TI  - Lead nitrate induced apoptosis in alveolar macrophages from rat lung.
AB  - In this work we have attempted to characterize the programmed cell death
      (apoptosis) in alveolar macrophages exposed to various concentrations of lead
      nitrate. It was found that after 3 h of exposure a significant increase in
      superoxide anion production was observed, i.e. the number of trypan blue -
      exculding cells, was unchanged (< or = 95%) with any dose of lead employed.
      Agarose gel electrophoresis and diphenylamin reaction analysis revealed the
      occurrence of internucleosomal DNA fragmentation evaluated using cytological
      analysis by fluorescence dyes, suggesting that lead nitrate at low concentrations
      and short periods of exposure leads macrophages into apoptosis. However, time
      course studies showed that beyond 3 h, toxicity occurs, which could be attenuated
      by phosphodiesterase inhibitors, such as caffeine, suggesting a possible
      mechanism involving cAMP.

PMID- 10967407
TI  - Dose and time dependent effects of caffeine on superoxide release, cell survival
      and DNA fragmentation of alveolar macrophages from rat lung.
AB  - In this study, the effect of two concentration ranges of the cAMP
      phosphodiesterase inhibitor, caffeine, on alveolar macrophage function was
      investigated by measuring survival rate, superoxide anion production and DNA
      fragmentation. The results show caffeine induced apoptosis in alveolar
      macrophages in a dose dependent manner. The survival rate of the cells exposed to
      low concentrations of caffeine (<5 mM) increased remarkably with a peak at 2.5
      mM. At this concentration, caffeine failed to affect superoxide anion production
      and DNA degradation. However, at higher concentrations (5-20 mM), at which the
      viability was higher than the control, a significant increase in both superoxide
      production and DNA degradation, as judged by agarose gel and diphenylamine
      reaction, was obtained for 3 and 24 h of culture. The effect of caffeine on
      survival rate was also time dependent. At low caffeine concentrations,
      macrophages survived with a viability of 90-97% after 3 days. At moderate
      concentrations, the cells maintained viability up to 24 h but at concentrations
      higher than 20 mM, caffeine inhibited cell survival and killed a fraction of the
      population. The results suggest that low concentrations of caffeine prevent
      apoptosis of macrophages, whereas at moderate concentrations caffeine induces
      apoptosis in these cells. The results are discussed in relation to the mechanism
      of cAMP.

PMID- 10967409
TI  - Dose-dependent apoptosis induced by low concentrations of methylmercury in murine
      splenic Fas+ T cell subsets.
AB  - Methylmercury chloride (MeHgCl) is known to induce cellular and humoral
      immunodeficiencies in mice. In this study, the involvement of lymphoid subset
      disorders due to low concentrations of methylmercury (0.001-1.0 microM) has been
      examined. Cytofluorometric analysis of splenic cells exposed in vitro to low
      concentrations of MeHgCl for 48 h revealed two distinct populations: the first
      expressed a typical lymphoid forward light scatter (FSC)/side light scatter (SSC)
      pattern (R1 region), and the second was characterized by a lower FSC and a higher
      SSC (R2 region). A dose-dependent shift of cells from R1 region toward R2 region
      was observed in splenic cells treated with MeHgCl. The apoptotic state of cells
      in the R2 region was confirmed by the TdT-mediated dUTP nick end labeling (TUNEL)
      assay. Analysis of DNA content in splenic lymphoid cells showed that low
      concentrations of MeHgCl increased both hypoploid cells and cells in G0-G1/S
      phase, both in the R1 and R2 regions. However, the numbers of cells in G0-G1/S
      and G2/M phases were decreased, but hypoploid cells increased in both regions due
      to exposure to 1 microM MeHgCl. MeHgCl-induced apoptosis disappeared when splenic
      cells were pretreated with anti-Fas antibodies, indicating that Fas expressing
      cells were the target cells for MeHgCl-mediated apoptosis. Furthermore, T cells
      from the V beta 8 family were found to be more sensitive to apoptosis induced by
      low concentrations of MeHgCl. Taken together, these results suggest that MeHgCl
      at low concentrations mediates the development of apoptosis in peripheral T cell
      via the Fas/FasL pathway.

PMID- 10967410
TI  - Beryllium-stimulated apoptosis in macrophage cell lines.
AB  - In vitro stimulation of bronchoalveolar lavage cells from patients with chronic
      beryllium disease (CBD) induces the production of TNF-alpha. We tested the
      hypothesis that beryllium (Be)-stimulated TNF-alpha might induce apoptosis in
      mouse and human macrophage cell lines. These cell lines were selected because
      they produce a range of Be-stimulated TNF-alpha. The mouse macrophage cell line
      H36.12j produces high levels of Be-stimulated TNF-alpha. The mouse macrophage
      cell line P388D.1 produces low, constitutive, levels of TNF-alpha and does not up
      regulate Be-stimulated TNF-alpha production. The DEOHS-1 human CBD macrophage
      cell line does not produce constitutive or Be-stimulated TNF-alpha. Apoptosis was
      determined by microscopic observation of propidium iodide stained fragmented
      nuclei in unstimulated and BeSO(4)-stimulated macrophage cell lines. BeSO(4)
      induced apoptosis in all macrophage cell lines tested. Beryllium-stimulated
      apoptosis was dose-responsive and maximal after 24 h of exposure to 100 microM
      BeSO(4). In contrast, unstimulated and Al(2)(SO(4))(3)-stimulated macrophage cell
      lines did not undergo apoptosis. The general caspase inhibitor BD-fmk inhibited
      Be-stimulated macrophage cell line apoptosis at concentrations above 50 microM.
      Our data show that Be-stimulated macrophage cell line apoptosis was caspase
      dependent and not solely dependent on Be-stimulated TNF-alpha levels. We
      speculate that the release of Be-antigen from apoptotic macrophages may serve to
      re-introduce Be material back into the lung microenvironment, make it available
      for uptake by new macrophages, and thereby amplify Be-stimulated cytokine
      production, promoting ongoing inflammation and granuloma maintenance in CBD.

PMID- 10967411
TI  - Bone-related mineral content of water samples collected on the Navajo
      reservation.
AB  - Although dairy food intake is low among the Navajo people, hip fracture rates are
      lower than in Caucasians. Genetic differences in bone density have been cited as
      the reasons for low fracture rates among Native Americans and other segments of
      the population. However, more detailed examination of mineral intakes suggests
      that environmental factors may provide part of the explanation for the lower
      fracture rates. Cultural practices such as the addition of ash to traditional
      foods and the high mineral content of water may provide much higher intakes of
      bone-related minerals than food intake surveys have previously reported. As part
      of a larger study to assess overall intake of minerals related to bone health and
      other conditions, water samples were collected from the Navajo reservation.
      Duplicates were collected at least one week apart from 53 sites including wells,
      springs, taps, and storage barrels and analyzed by atomic absorption and
      inductively coupled plasma spectrometry for a number of minerals. For average
      intakes of 2 l/day, water could provide up to 212 mg of calcium, 150 mg of
      magnesium and 8 mg of zinc. The combined contribution of mineral intakes provided
      by the addition of juniper ash to traditional foods, not genetic differences, may
      partially explain the lower fracture rates of the Navajo people. Further research
      in this area is required to confirm this hypothesis.

PMID- 10967421
TI  - Neurofibromatosis type 1.

PMID- 10967423
TI  - Diverse nuclear transport pathways regulate cell proliferation and oncogenesis.

PMID- 10967424
TI  - p21(WAF1/Cip1): more than a break to the cell cycle?

PMID- 10967425
TI  - The Eukaryotic Nucleus, 9-13 September 1999, Coolfont Conference Center, Berkeley
      Springs, WV, USA.

PMID- 10967426
TI  - Erratum to 'Molecular horizons of cancer therapeutics. 11th pezcoller Symposium'.

PMID- 10967427
TI  - Lyophilization and development of solid protein pharmaceuticals.
AB  - Developing recombinant protein pharmaceuticals has proved to be very challenging
      because of both the complexity of protein production and purification, and the
      limited physical and chemical stability of proteins. To overcome the instability
      barrier, proteins often have to be made into solid forms to achieve an acceptable
      shelf life as pharmaceutical products. The most commonly used method for
      preparing solid protein pharmaceuticals is lyophilization (freeze-drying).
      Unfortunately, the lyophilization process generates both freezing and drying
      stresses, which can denature proteins to various degrees. Even after successful
      lyophilization with a protein stabilizer(s), proteins in solid state may still
      have limited long-term storage stability. In the past two decades, numerous
      studies have been conducted in the area of protein lyophilization technology, and
      instability/stabilization during lyophilization and long-term storage. Many
      critical issues have been identified. To have an up-to-date perspective of the
      lyophilization process and more importantly, its application in formulating solid
      protein pharmaceuticals, this article reviews the recent investigations and
      achievements in these exciting areas, especially in the past 10 years. Four
      interrelated topics are discussed: lyophilization and its denaturation stresses,
      cryo- and lyo-protection of proteins by excipients, design of a robust
      lyophilization cycle, and with emphasis, instability, stabilization, and
      formulation of solid protein pharmaceuticals.

PMID- 10967428
TI  - In vivo evaluation of doxorubicin carried with long circulating and remote
      loading proliposome.
AB  - Long circulating and remote loading proliposome (LRP-L) was a kind of transparent
      solution and composed of soybean phosphatidylcholine (SPC), cholesterol,
      polyethylene glycol derivative of distearoylphosphatidyl ethanolamine (PEG-DSPE)
      and oleic acid sodium salt. When LRP-L was mixed with 0.9% NaCl aqueous solution
      containing doxorubicin (DXR), liposomes formed and automatically loaded DXR, in
      which sonication and extruders were not needed. The average diameter of the
      liposomal DXR in saline was 129.0+/-1.9 nm and the encapsulation efficiency was
      98.1+/-0.6%. The pharmacokinetics, biodistribution, acute toxicity and anticancer
      effect of DXR carried with LRP-L (LRP-L-DXR) were studied. The plasma
      concentration-time curves of DXR were best fitted to the triexponential decay
      curves. The area under the plasma concentration-time curve (AUC) of LRP-L-DXR was
      22 and five times of free DXR (F-DXR) and conventional cardiolipin liposomal DXR
      (CL-DXR), respectively. Following i.v. administration, the biodistribution of LRP
      L-DXR in the heart and the liver, unlike that of CL-DXR, was not greater than
      that of F-DXR. However, the biodistribution of LRP-L-DXR in the spleen was less
      than that of CL-DXR and greater than that of F-DXR. The acute toxicity of LRP-L
      DXR was decreased compared with that of F-DXR. The anticancer effect of LRP-L-DXR
      was significantly increased compared with that of F-DXR in the ascitic M5076
      tumor model of C57BL/6 mice and had no significant difference compared with that
      of doxorubicin HCl liposome injection (Doxil).

PMID- 10967429
TI  - Tensile strength of tablets containing two materials with a different compaction
      behaviour.
AB  - The tensile strength of tablets compressed from binary mixtures is in general not
      linearly related to the strength of tablets prepared from single materials; in
      many cases it shows a decreased tensile strength relative to interpolation. The
      materials used in this study, sodium chloride and pregelatinised starch, are both
      plastically deforming materials, but have a different densification and
      relaxation behaviour. The yield pressure of the binary mixtures shows an almost
      linear relationship. As an effect of their lower yield pressure, starch particles
      yield earlier than sodium chloride particles. The following enclosure prevents
      some sodium chloride particles to yield or crack. The relaxation of the tablets
      is higher than the relaxation calculated by linear interpolation of the
      relaxation behaviour of the two pure materials. The difference between the
      measured porosity expansion and the data obtained by linear interpolation can be
      considered as a measure for the reduced interparticle bonding. SEM-photographs
      indicate that the reduced interparticle bonding is caused by the low adhesive
      forces. The measured decrease of the tensile strength of the tablets is also
      considered to be the result of reduced interparticle bonding. In this paper it is
      shown that there exists a similar relationship between the tensile strength
      reduction and the percentage of starch on the one hand and the extra porosity
      expansion and the starch percentage on the other hand.

PMID- 10967430
TI  - Strategies for maintaining the particle size of peptide DNA condensates following
      freeze-drying.
AB  - The particle size of peptide DNA condensates were studied after freeze-drying and
      rehydration as a function of sugar excipient, concentration, pH, DNA
      concentration, and peptide condensing agent. In the absence of an excipient,
      freeze-dried 50 microg/ml AlkCWK(18) (iodoacetic acid alkylated Cys-Typ-Lys(18))
      DNA condensates formed large fibrous flocculates on rehydration. Of the sugars
      tested as lyoprotectants, sucrose proved most effective at preserving particle
      size during rehydration. The addition of 5 wt/vol% sucrose preserved a mean
      particle diameter of less than 50 nm during rehydration of AlkCWK(18) DNA
      condensates prepared at DNA concentrations up to 200 microg/ml; however, higher
      DNA concentrations led to the formation of insoluble fibrous flocculates.
      Substitution of polyethylene glycol (PEG)-CWK(18) as a DNA condensing peptide
      eliminated the need for sucrose, resulting in peptide DNA condensates that
      retained particle size when rehydrated in water or normal saline at
      concentrations up to 5 mg/ml. The results suggest that sucrose functions
      primarily as a bulking agent during freeze-drying that only preserves the
      particle size of AlkCWK(18) DNA condensates up to a maximum concentration of 200
      microg/ml. Alternatively, the steric layer created on the surface of PEG-CWK(18)
      DNA condensates provides far more efficient lyoprotection, preserving their
      particle size at a concentration of 5 mg/ml without a bulking agent.

PMID- 10967431
TI  - Characterization of thermosensitive chitosan gels for the sustained delivery of
      drugs.
AB  - The aim of this study was to investigate the physical properties of a
      chitosan/glycerophosphate (GP) thermosensitive solution which gels at 37 degrees
      C and evaluate the in vitro release profiles of different model compounds. The
      gelation rate was dependent on the temperature and on the chitosan deacetylation
      degree. The solution containing 84%-deacetylated chitosan could be stored 3
      months at 4 degrees C without apparent change in viscosity. The in vitro release
      profiles of the model compounds depended on the presence of GP in the chitosan
      solution, on their molecular weight and on the presence of lysozyme in the
      release media. They were not affected by the electrostatic charge of the model
      compound when present at low concentrations. During the first 4 h, the release
      was accompanied by a substantial loss of the gel weight which was mainly
      attributed to the leaching of water and excess GP. Scanning electron micrographs
      revealed that the solutions yield gels with a highly porous structure after 24 h
      of exposure to a continuous flow of phosphate buffered saline. These results
      indicate that the chitosan/GP thermosensitive solutions gel rapidly at body
      temperature, can remain in the sol state at 4 degrees C and can sustain the
      delivery of macromolecules.

PMID- 10967432
TI  - Interactions between liposomes and hydroxypropylmethylcellulose.
AB  - The characteristics of the adsorption process of hydroxypropylmethylcellulose
      (HPMC) of molecular weight 35400 Da and nominal viscosity 100 cps onto liposomes
      prepared with different egg lecithin-cholesterol molar ratios were examined.
      Adsorption isotherms were constructed and analysed to investigate the mechanisms
      implicated in the incorporation of the polymer to the interface. Only the
      isotherms obtained with cholesterol-free liposomes were fitted with Langmuir
      model. When cholesterol is present in the composition they present a sigmoidal
      slope. The mechanism of adsorption depends on liposome composition being the main
      force that drives polymer adsorption of hydrophobic nature. The apparent volumes
      of HPMC indicate that the conformation of the adsorbed macromolecules depends on
      liposome composition. Hydration enthalpy values show that adsorbed polymers do
      not give more hydrophilic systems after freeze-drying as expected with the
      hydrophilic characteristics of the HPMC.

PMID- 10967433
TI  - Microbiological assay for terbinafine hydrochloride in tablets and creams.
AB  - The optimization of a microbiological assay, applying the cylinder-plate method,
      for the determination of the antifungal terbinafine hydrochloride is described.
      Using a strain of Aspergillus flavus ATCC 15546 as the test organism, terbinafine
      hydrochloride at concentrations ranging from 0.125 to 0.5 microg ml(-1) could be
      measured in tablets and creams. A prospective validation of the method showed
      that the method was linear (r=0. 9999), precise (intra-day: CV=0.48%-tablets and
      0.43%-creams; inter-day: CV=0.98%-tablets and 0.64%-creams) and accurate (it
      measured the added quantities). The method shows results that confirm its
      precision, not differing significantly the others methods described in the
      literature. We conclude that the microbiological assay is satisfactory for
      quantitation of in vitro antifungal activity of terbinafine.

PMID- 10967434
TI  - The degradation pathways of glucagon in acidic solutions.
AB  - OBJECTIVE: Glucagon is a 29 amino acid peptide hormone that exhibits degradation
      via both chemical and physical pathways. The objective of the studies reported
      herein was to identify the degradation products and scheme for glucagon
      hydrolysis in acidic solutions. METHODS: Solutions of glucagon in 0.01 N HCl (pH
      2.5) were degraded at 60 degrees C for 70 h. One isocratic and two gradient RP
      HPLC methods were developed to separate the degradation products. Structure
      elucidation of the separated peaks was achieved using amino acid sequencing,
      amino acid analysis, and mass spectrometry. Degradation was carried out in the pH
      range 1.5-5 to check for changes in degradation scheme with pH. Authentic samples
      of degradation products were degraded under similar acidic conditions to confirm
      precursor successor relationships in the degradation scheme. RESULTS: Sixteen
      major degradation products were isolated and identified. The major pathways of
      degradation were found to be aspartic acid cleavage at positions 9, 15, and 21
      and glutaminyl deamidation at positions 3, 20, and 24. Cleavage occurred on both
      sides of Asp-15 but only on the C-terminal side of Asp-9 and Asp-21. Deamidation
      of the Asn residue at position 28 was not detected.

PMID- 10967435
TI  - Synchrotron X-ray investigations into the lamellar gel phase formed in
      pharmaceutical creams prepared with cetrimide and fatty alcohols.
AB  - Semisolid liquid paraffin-in-water emulsions (aqueous creams) prepared from
      cetrimide/fatty alcohol mixed emulsifiers, and ternary systems formed by
      dispersing the mixed emulsifier in controlled percentages of water were examined
      as they aged using a combination of low and high angle X-ray diffraction
      measurements (Daresbury Laboratory Synchrotron Radiation Source). The results
      were correlated with the rheological properties measured in earlier studies. The
      cationic emulsifying wax showed phenomenal swelling in water. The reflection that
      incorporates interlamellar water increased continuously from 74 A at 28% water to
      over 500 A at 93% water. The trend was not influenced by the method of
      incorporation of the components and swollen lamellar phase was also identified in
      the corresponding emulsion. The swelling, which was due to electrostatic
      repulsion, was suppressed by salt and was reduced when the surfactant counterion
      was changed from Br(-) to Cl(-). Changes in rheological properties on storage and
      in the presence of salt were correlated with changes in water layer thickness.
      High angle diffraction confirmed that the hydrocarbon bilayers were in the
      hexagonal alpha-crystalline mode of packing. Ternary systems and creams prepared
      from pure alcohols, although initially semisolid, were rheologically unstable and
      broke down. Low angle X-ray study into the kinetics of structure breakdown showed
      that the swollen lamellar gel phase formed initially swells even further on
      storage before separating.

PMID- 10967436
TI  - Stabilization and sustained-release effect of misoprostol with methacrylate
      copolymer.
AB  - The use of ammonio methacrylate copolymer (Eudrgit RS, RL) to form a sustained
      release solid dispersion of Misoprostol can improve and enhance two important
      physical and chemical properties of Misoprostol. First, the solid dispersion
      matrix formed by the copolymer can protect Misoprostol from being degraded by
      water so that its stability is improved. Second, Misoprostol can be slowly
      released by diffusion from the copolymer matrix. Accelerated stability studies of
      Misoprostol-Eudragit solid dispersion after storing at various temperatures for
      different time periods were carried out. According to high performance liquid
      chromatography (HPLC) analyses, the stability of Misoprostol in a series of
      Eudragit appeared significantly improved at different ratios. The Misoprostol
      Eudragit dispersion can be used in a powder form, filled in capsules, or
      compressed into tablets. The dissolution profiles of Misoprostol-Eudragit solid
      dispersion and its tablets in water, pH 1. 2, 4.5 and 6.8, dissolution media show
      that this stable solid dispersion is a sustained-release type.

PMID- 10967437
TI  - Controlled release of terbinafine hydrochloride from pH sensitive
      poly(acrylamide/maleic acid) hydrogels.
AB  - Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and
      from pH sensitive poly(acrylamide/maleic acid) (P(AAm/MA)) hydrogels were
      investigated. P(AAm/MA) hydrogels were prepared by irradiating the ternary
      mixtures of AAm/MA/and water by gamma-rays at ambient temperature. Antifungal
      drug, TER-HCl containing hydrogels, at different drug to polymer ratios, was
      prepared by direct adsorption method. The influence of MA content in the gel on
      the adsorption capacities of hydrogel and the effect of pH on the releasing
      behavior of TER-HCl from gel matrix were investigated. Terbinafine adsorption
      capacity of hydrogels are found to increase from 2 to 38 mg TER-HCl per g dry gel
      with increasing amount of MA in the gel system. In vitro drug release studies in
      different buffer solutions show that the basic parameters affecting the drug
      release behavior of hydrogel are the pH of the solution and MA content of
      hydrogel.

PMID- 10967438
TI  - Development of spray-dried acetaminophen microparticles using experimental
      designs.
AB  - Experimental factorial designs were built to investigate the effects of five
      parameters on production yields and moisture contents of spray-dried products.
      These factors concerned both the solution feed (drug concentration, colloidal
      silica concentration and polymer/drug ratio) and the spray dryer (inlet
      temperature and feed rate). Three formulations containing cellulose derivatives
      and acetaminophen were tested. The aim of the study was to optimize the operating
      conditions to maximize production yields while minimizing moisture contents.
      First screening experiments consisting of fractional factorial designs revealed
      the most significant factors to be inlet temperature, feed rate and their
      interaction for both formulations containing sodium carboxymethylcellulose and
      feed rate and colloidal silica concentration for the formulation containing
      microcrystalline cellulose. Then, the optimal operating conditions were estimated
      by response surface methodology. Central rotational composite designs showed
      quadratic models were adequate. New assays were carried out using these last
      conditions to evaluate both the repeatability and reproducibility of the spray
      drying technique. Yields above 80% and moisture content of approximately 1% were
      reached. The characterization of microparticles revealed the poor flowability of
      the spray-dried products due to significant cohesiveness and very small size
      (less than 55 microm).

PMID- 10967439
TI  - Polysaccharide coated liposomes for oral immunization--development and
      characterization.
AB  - Polysaccharide coated liposomes were prepared, characterized and evaluated for
      their potential use in oral immunization. Liposomes were prepared by reverse
      phase evaporation method. Bovine serum albumin (BSA) was chosen as the model
      antigen. Pulluan, a naturally occurring polysaccharide produced by a yeast like
      fungus, was chemically modified into its palmitoyl derivative (O
      palmitoylpullulan; OPP) and was used for coating of the liposomes. The
      synthesized OPP was characterized by IR and NMR spectroscopy. The liposomes
      prepared were characterized for their size, shape, surface charge, encapsulation
      efficiency and stability in simulated gastric fluid. The immune stimulating
      activity was studied by measuring the serum IgA and IgG following oral
      administration of the prepared polysaccharide coated liposomes. Similarly, other
      formulations were studied and the results were compared. BSA loaded liposomes
      coated with OPP and plain polysaccharide could produce better IgG and IgA titre
      levels as compared to plain alum adsorbed BSA. The plain liposomes containing BSA
      could however produce significantly higher IgG and IgA levels as compared to
      equivalent BSA-alum based oral immunization. The results indicate that chemically
      modified polysaccharide coated liposomes can be used as a potential adjuvants for
      effective oral immunization.

PMID- 10967440
TI  - Compressed xanthan and karaya gum matrices: hydration, erosion and drug release
      mechanisms.
AB  - Directly compressed matrices were produced containing either xanthan gum or
      karaya gum as a release-controlling agent. These swellable hydrophilic natural
      gums were used to control the release of varying proportions of two model drugs,
      caffeine and diclofenac sodium, which have different solubilities in aqueous
      medium. Gum erosion, hydration and drug release studies were carried out using a
      dissolution apparatus (basket method) at two agitation speeds. Xanthan gum
      displayed a high degree of swelling due to water uptake and a small degree of
      erosion due to polymer relaxation. Neither agitation speed nor drug solubility
      had any significant effect on water uptake, but matrices with the lower
      proportion of gum produced a lesser degree of hydration. In contrast, karaya gum
      displayed a much lower hydration capacity and a higher rate of erosion, both
      markedly affected by agitation speed. Drug release from xanthan and karaya gum
      matrices depended on agitation speed, solubility and proportion of drug. Both
      xanthan and karaya gums produced near zero order drug release with the erosion
      mechanism playing a dominant role, especially in karaya gum matrices.

PMID- 10967442
TI  - Whisker growth of l-menthol in coexistence with various excipients.
AB  - The purpose of the present study was to clarify the mechanism for l-menthol
      whisker growth. l-Menthol was mixed with an excipient, and the interaction was
      examined by IR measurement, thermal analysis and powder X-ray diffraction. Then
      we examined the involvement of the capillary condensation using the pore size
      distribution measurement. By mixing l-menthol with an excipient with whisker
      growth, the hydroxyl group stretching band of l-menthol was shifted to the higher
      wavenumber in the IR spectrum, the melting point and heat of fusion of l-menthol
      became lower in the thermal analysis, and the diffraction intensity of l-menthol
      became lower in the powder X-ray diffraction. The excipients with whisker growth
      showed the tendency to have the meso-pore involved in the capillary condensation
      in the pore size distribution measurement. From the above results, the whisker
      growth mechanism is considered as follows. When l-menthol was mixed with an
      excipient with whisker growth, the crystallinity of l-menthol was lowered and the
      vapor pressure was increased by the interaction mainly consisting of the hydrogen
      bond. The generated l-menthol vapor entered meso-pore, the saturated vapor
      pressure was lowered by the capillary condensation, and the nucleation occurred.
      The vapor was further supplied, generating the growth of whisker.

PMID- 10967441
TI  - Hydrophobic ion pair formation between leuprolide and sodium oleate for sustained
      release from biodegradable polymeric microspheres.
AB  - Leuprolide acetate, an analogue of luteinizing hormone-releasing hormone (LH-RH),
      was hydrophobically ion paired with a long chain fatty acid, sodium oleate, in an
      aqueous solution. Solution behaviors of the complex formed between leuprolide and
      sodium oleate were investigated in terms of aqueous solubility, turbidity,
      particle size, and zeta potential as a function of molar ratio between the two
      species. It was found that with increasing the stoichiometric molar amounts of
      sodium oleate to leuprolide approached up to 2.5-3, the solution became gradually
      turbid with increasing particle sizes, indicating leuprolide precipitation as a
      result of hydrophobic ion pairing. On the other hand, beyond that critical molar
      ratio range, the solution turned into clear with much reduced particle size,
      indicative of micelle formation. The hydrophobically modified leuprolide-oleate
      complex was lyophilized and directly encapsulated within biodegradable poly(D, L
      lactic-co-glycolic acid) (PLGA) microspheres via a single oil-in-water (O/W)
      emulsion method. Microsphere morphology, leuprolide release behavior, and polymer
      mass erosion profiles were examined in comparison to the PLGA microspheres
      prepared with free leuprolide.

PMID- 10967443
TI  - Lipid and ultrastructural characterization of reconstructed skin models.
AB  - The study aimed at evaluating tissue architecture and quality of the permeability
      barrier in commercially available reconstructed human skin models; EpiDerm,
      SkinEthic and Episkin in comparison to native tissue. For this purpose, tissue
      architecture was examined by electron microscopy and epidermal lipid composition
      was analyzed by HPTLC. Stratum corneum lipid organization was investigated by
      electron microscopy in combination with RuO(4) post-fixation and by SAXD.
      Ultrastructurally, the overall tissue architecture showed high similarities with
      native epidermis. In the stratum corneum extracellular space, lipid lamellae
      consisting of multiple alternating electron-dense and electron-lucent bands were
      present. This regular pattern was not seen throughout the whole stratum corneum
      probably due to the observed irregular lamellar body extrusion in some areas.
      Lipid analyses revealed the presence of all major epidermal lipid classes.
      Compared with native epidermis the content of polar ceramides 5 and 6 was lower,
      ceramide 7 was absent, and the content of free fatty acids was very low. These
      differences in lipid composition may account for differences observed in SAXD
      pattern of Episkin and EpiDerm penetration models. In the latter only the long
      distance periodicity unit of about 12 nm was observed and the short periodicity
      unit was missing. In conclusion, all three skin models provide a promising means
      for studying the effects of topically applied chemicals, although the observed
      deviations in tissue homeostasis and barrier properties need to be optimized.

PMID- 10967444
TI  - Spinal biopharmaceutics of bupivacaine and lidocaine by microdialysis after their
      simultaneous administration in rabbits.
AB  - The aim of the present study was to determine the intrathecal bioavailability of
      a mixture of lidocaine and bupivacaine in a rabbit model of spinal anesthesia by
      using the microdialysis technique. Catheter and microdialysis probe were inserted
      under control of the view either in the epidural or in the intrathecal space.
      First, the epidural disposition of the mixture of bupivacaine and lidocaine was
      studied after epidural administration. Then, the intrathecal and plasma
      dispositions of bupivacaine and lidocaine were investigated following intrathecal
      or epidural administration. The epidural clearance of bupivacaine was higher than
      that of lidocaine, suggesting a more significant uptake of bupivacaine into the
      systemic circulation and/or into the CSF. The intrathecal bioavailability of
      bupivacaine and lidocaine was 12.3 and 17.9%, respectively, while it was 5.5 and
      17.7% following the separate administration of each agent [Clement, R.,
      Malinovsky, J.M., Le Corre, P., Dollo, G., Chevanne, F., Le Verge, R., 1999.
      Cerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and
      lidocaine following intrathecal and epidural administrations in rabbits using
      microdialysis. J. Pharmacol. Exp. Ther. 289, 1015-21]. After intrathecal
      administration, a decrease in C(max) and AUC values was observed for bupivacaine
      in comparison with the separate administration. Moreover, after epidural
      administration, the systemic resorption was slower and lower, especially for
      bupivacaine. Such a reduction in the systemic absorption of bupivacaine might
      increase its intrathecal bioavailability, resulting from a vasoconstrictor effect
      of lidocaine reducing the systemic absorption of bupivacaine from the epidural
      space leading to an increase of its extent of absorption through meninges into
      CSF although its absorption rate was not modified.

PMID- 10967445
TI  - Preparation in high-shear mixer of sustained-release pellets by melt
      pelletisation.
AB  - The preparation of sustained-release pellets by melt pelletisation was
      investigated in a 10-l high shear mixer and ternary mixtures containing stearic
      acid as a melting binder, anhydrous lactose as a filler and theophylline as a
      model drug. A translated Doehlert matrix was applied for the optimisation of
      process variables and quality control of pellets characteristics. After
      determination of size distribution, the pellets were characterised with scanning
      electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis.
      Finally, the in vitro release from every single size fraction was evaluated and
      the release mechanism was analysed. Since the drug release rate decreased when
      enhancing the pellet size fraction, the 2000-microm fraction, exhibiting a
      substantially zero-order release, was selected for further in vivo biovailability
      studies. These data demonstrated that pellets based on the combination of stearic
      acid and lactose can be used to formulate sustained release pellets for
      theophylline.

PMID- 10967446
TI  - The influence of Span20 on stratum corneum lipids in langmuir monolayers:
      comparison with Azone.
AB  - Recently we have proved that Span 20 has the same enhancer effect as Azone on in
      vitro percutaneous penetration of lipophilic compounds (logP(oct) from 1.34 to
      2.33). The purpose of this work is to study the interactions of Span 20 with
      stratum corneum lipids monolayers and to compare them with Azone. The surface
      pressure-area characteristics of Span 20 in mixed monolayers with different model
      lipids (ceramides, cholesterol, free fatty acids and two mixtures of
      ceramides+cholesterol, and ceramides+cholesterol+free fatty acids) in similar
      proportions to that which exists in human stratum corneum lipids were recorded as
      compression isotherms at 25 degrees C. Azone was also investigated on
      monomolecular films of some of these lipids. The results indicate that the effect
      exerted upon lipid packing by the Span 20 correspond, as in the case of Azone, to
      increased fluidity within monolayers. To quantify and compare the effect of Span
      20 and Azone, the compressibility of enhancer-lipid model mixed monolayers was
      calculated, and expressed as a function of mole fraction of enhancer present on
      the films. Statistical comparison of the results obtained from both enhancers
      shows that they are equally potent in their interaction with the lipid models
      assayed. These models, if restricted, seem to be good for predict the activity
      and potency of percutaneous enhancers on the fluididity of the lipidic structure
      of the stratum corneum.

PMID- 10967447
TI  - Determination of incorporated amounts of poly(ethylene glycol)-derivatized lipids
      in liposomes for the physicochemical characterization of stealth liposomes.
AB  - We describe a method for determining incorporated amounts of poly(ethylene
      glycol) (PEG)-derivatized lipids in liposomes for the physicochemical
      characterization of PEG-coated liposomes. This method is based on the
      spectrophotometric determination of complexes of polyethers with sodium ions
      after their extraction as picrates into 1,2-dichloroethane, developed by Favretto
      for measuring levels of polyoxyethylene alkylphenyl-ether non-ionic surfactants
      in waste water. The same assay was applied to the estimation of PEG-derivatized
      lipids in liposomes and percent incorporation of PEG-derivatized lipids into
      liposomes was successfully determined. To prevent the interference from liposomal
      lipids other than PEG-derivatized lipids in this assay, liposomal samples were
      diluted at least to a concentration of less than 0.2 mM. The percent
      incorporation of PEG-lipids varied, depending on the molecular weight of PEG and
      anchor acyl chain length in PEG-lipids and it was suggested that the percent
      incorporation of PEG-lipids into liposomes would be a good parameter of quality
      control of PEG-liposomes in manufacturing facility and the picrate method used in
      the present study allows for the determination of this parameter without the need
      for hazardous radioisotopes.

PMID- 10967448
TI  - Adhatoda vasica: a critical review of ethnopharmacological and toxicological
      data.
AB  - Adhatoda vasica (L.) Nees is a well-known plant drug in Ayurvedic and Unani
      medicine. It has been used for the treatment of various diseases and disorders,
      particularly for the respiratory tract ailments. During the last 20 years,
      several scientific reports on oxytocic and abortifacient effects of vasicine and
      alkaloid derived from the plant have appeared. This leads to questions concerning
      the safety of A. vasica as a herbal medicine. In this article, the major data on
      traditional uses as well as ethnopharmacological and toxicological studies, both
      published and unpublished, are reviewed and commented upon. The data have been
      evaluated from the point of view of correctness, reliability, relevance and
      importance for the overall evaluation of the safety of A. vasica.

PMID- 10967449
TI  - Hypoglycemic effect of extracts and fractions from Psacalium decompositum in
      healthy and alloxan-diabetic mice.
AB  - The hypoglycemic effect of the hexane, methanol and water extracts obtained from
      roots of Psacalium decompositum (Asteraceae) was investigated in fasting healthy
      mice. Only the water extract significantly reduced blood glucose in a dose
      dependent manner in normal mice after intraperitoneal administration (P<0.05).
      This water extract was macerated with methanol obtaining a precipitate (WMP
      fraction), and it was studied in healthy and alloxan-diabetic mice. The WMP
      fraction showed significant hypoglycemic activity in healthy and mild diabetic
      mice, but the administration of this fraction to animals with severe diabetes did
      not cause any significant decrease in blood glucose levels. Two polysaccharide
      components isolated from WMP fraction showed hypoglycemic effect when tested in
      healthy mice.

PMID- 10967450
TI  - Chemopreventive activity of Ocimum sanctum seed oil.
AB  - The seed oil of Ocimum sanctum was evaluated for chemopreventive activity against
      subcutaneously injected 20-methylcholanthrene induced-fibrosarcoma tumors in the
      thigh region of Swiss albino mice. Supplementation of maximal tolerated dose (100
      microl/kg body weight) of the oil significantly reduced 20-methylcholanthrene
      induced tumor incidence and tumor volume. The enhanced survival rate and delay in
      tumor incidence was observed in seed oil supplemented mice. Liver enzymatic
      (superoxide dismutase, catalase, glutathione-S-transferase), non-enzymatic
      antioxidants (reduced glutathione) and lipid peroxidation end product,
      malondialdehyde levels were significantly modulated with oil treatment as
      compared to untreated 20-methylcholanthrene injected mice. The results of this
      study suggest that the potential chemopreventive activity of the oil is partly
      attributable to its antioxidant properties. The chemopreventive efficacy of 100
      microl/kg seed oil was comparable to that of 80 mg/kg of vitamin E.

PMID- 10967451
TI  - Phenolic compounds and antioxidant activities of buckwheat (Fagopyrum esculentum
      Moench) hulls and flour.
AB  - The interest of polyphenolics as therapeutic agents against diseases involving
      radical damage is growing. The phenolic contents of the hulls and flour from the
      seeds of Fagopyrum esculentum (French variety 'La Harpe') (total phenols,
      flavonoids, total flavanols, oligomeric proanthocyanidins) are compared with the
      antioxidative effects of the extracts against reactive oxygen species: hydrogen
      peroxide, hypochlorous acid, superoxide anion. The higher efficiency of the flour
      extract can be related to its higher flavanolic content rather than to flavonoids
      which are predominant in the hull extract.

PMID- 10967452
TI  - Antifungal activity of anthraquinone derivatives from Rheum emodi.
AB  - Rhein, physcion, aloe-emodin and chrysophanol isolated from Rheum emodi rhizomes
      exhibited antifungal activity against Candida albicans, Cryptococcus neoformans,
      Trichophyton mentagrophytes and Aspergillus fumigatus (MIC 25-250 microg/ml).

PMID- 10967453
TI  - Comparison of relative antioxidant activities of British medicinal plant species
      in vitro.
AB  - We have determined the relative levels of endogenous antioxidant activity in a
      range of British medicinal plant species (representative of a variety of plant
      families, selected on the basis of their widespread use in traditional herbal
      medicine), via competitive scavenging of the ABTS(z.rad)(+) or O(2)(-)(z.rad)
      radicals in vitro. A number of plant species with appreciable levels (i.e.
      greater than or comparable with the activity in corresponding extracts of Ginkgo
      biloba or Panax ginseng, as recognised phytological sources of antioxidant
      activity) of antioxidant activity against the ABTS(z.rad)(+) radical were
      identified as potentially novel sources of free radical scavenging compounds;
      however none of these extracts showed measurable antioxidant activity when
      assayed against the O(2)(-)(z.rad) radical. It, therefore, follows that any
      comparative determination of antioxidant activity should clearly define the
      radical species and assay method employed. For those extracts showing activity
      against the ABTS(z.rad)(+) radical, in general, it was not possible to predict
      the potential antioxidant capacity of a given plant species (or the most active
      part of the plant) on a taxonomical basis, or from its use in traditional or
      modern medicine. In the longer term further characterisation of the active
      compounds from plant species with appreciable antioxidant activity identified in
      the present investigation may prove of value for treatment of disorders such as
      Alzheimer's disease, in which free radical induced tissue damage has been
      implicated.

PMID- 10967454
TI  - Effects of aqueous extracts of Apocynum venetum leaves on spontaneously
      hypertensive, renal hypertensive and NaCl-fed-hypertensive rats.
AB  - Effects of aqueous extracts of Apocynum venetum leaves (Luobuma extracts) on the
      blood pressure were evaluated in hypertensive animal models, such as
      spontaneously hypertensive rats (SHR), renal hypertensive rats and NaCl-induced
      hypertensive rats. In SHR, administration of Luobuma (heat-processed and
      unprocessed leaves) extracts at a dose of 70 mg/rat per day significantly
      decreased the systolic blood pressure value, but their decreasing effects were
      weaker than that of captopril. The urine volume, and the urinary Na(+), K(+) and
      protein excretions were not significantly different between Luobuma-treated and
      untreated groups. In 3/4 nephrectomized rats, the Luobuma extracts significantly
      decreased the systolic blood pressure value, accompanied by significant increases
      of the urine volume and the urinary Na(+) and K(+) excretions. Furthermore, they
      decreased the blood urea nitrogen (BUN) level. In NaCl-induced hypertensive rats,
      the Luobuma extract decreased the systolic blood pressure value. However, it did
      not change the urinary excretions of Na(+), K(+) and protein. The BUN level was
      lower than that of control rats, but the serum total cholesterol (TC) level did
      not changed. From these findings, the Luobuma extracts have an anti-hypertensive
      effect, possibly due to amelioration of the kidney functions in the three
      experimental animal models.

PMID- 10967455
TI  - Hydroalcoholic extract and fractions of Davilla rugosa Poiret: effects on
      spontaneous motor activity and elevated plus-maze behavior.
AB  - Davilla rugosa Poiret is commonly used in Brazilian folk medicine. The use as
      stimulant induced us to study the effects on motor activity and anxiety using an
      open-field and an elevated plus-maze, respectively. The hydroalcoholic extract of
      the stems (HE) was fractionated with chloroform (CF), chloroform/ethyl acetate
      (CAF), ethyl acetate (AF), ethyl acetate/ethanol (AEF), ethanol (EF) and
      ethanol/water (EWF). Rats were treated orally with HE (7.5, 15, 30 or 60 mg/kg)
      or fractions (15 mg/kg). In the open-field, HE (15 mg/kg), AEF, EF and EWF
      increased locomotion frequency and decreased immobility time; the contrary was
      observed with 30 and 60 mg/kg of HE. These doses also increased defecation. No
      effects were observed with 7.5 mg/kg of HE, CF, CAF or AF, except for an increase
      in defecation induced by AF. In the elevated plus-maze, total entries and number
      of entries into the open and closed arms and the time spent in the open arms and
      its percentage were increased only with 15 mg/kg of HE. The open-field results
      suggest that the drug increases motor activity (stimulant effect) and that the
      active components are in the three more polar fractions. An anxiolytic effect was
      observed only with the HE.

PMID- 10967456
TI  - Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in
      streptozotocin-diabetic rats.
AB  - The present study was designed to investigate the hypoglycemic and hypolipidemic
      activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae,
      Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal
      hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose
      tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the
      effect of repeated administration of an ethanolic extract of Averrhoa bilimbi
      (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125
      mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin,
      ABe significantly lowered blood glucose by 50% and blood triglyceride by 130%
      when compared with the vehicle. ABe also significantly increased the HDL
      cholesterol concentrations by 60% compared with the vehicle. ABe thus
      significantly increased the anti-atherogenic index and HDL-cholesterol/total
      cholesterol ratio. However, like metformin, ABe did not affect total cholesterol
      and LDL-cholesterol concentrations, but significantly reduced the kidney lipid
      peroxidation level. These data show that ABe has hypoglycemic,
      hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in
      STZ-diabetic rats.

PMID- 10967457
TI  - Shibimijihwang-tang elevates intracellular ATP and choline content in the
      cerebral cortex of ovariectomized rats.
AB  - Shibimijihwang-tang (SJT) has been used traditionally to improve systemic blood
      circulation and biological energy production in patients with circulatory and
      neuronal diseases. The object of this study is to determine the effect of SJT
      extract on the intracellular adenosine triphosphate (ATP) and choline content in
      the cerebral cortex of ovariectomized (OVX) rats. Bilateral ovaries of 8-week-old
      rats were removed. Rats were maintained for 12 weeks to deplete ovarian steroid
      hormones, followed by treatment with SJT at 500 mg/kg body weight per day for 12
      weeks. High rate of body weight increase in the OVX rats was markedly reduced by
      treatment with SJT, but the change in body weight of normal rats was not affected
      by it. SJT also significantly reduced the decline of cerebral weight in the OVX
      rats (P<0.05). Tissue glucose content in the cerebral cortex of OVX rats was
      significantly increased by SJT treatment (P<0.05). A decline in cerebral ATP
      content in OVX rats was dramatically restored by SJT administration (P<0.01), but
      SJT did not change the cerebral ATP content in normal rats. Cerebral choline
      content also declined following ovariectomy. This reduction was significantly
      elevated by SJT treatment (P<0.05), but SJT did not affect the change in cerebral
      choline in normal rats. Taken together, these results demonstrate that SJT can
      reduce the decrease in brain weight, cerebral ATP and choline content caused by
      deprivation of ovarian steroid hormones. This suggests that pharmacological
      properties of SJT may play a role in improvement of reduced cerebral energy
      production and cholinergic neurotransmitter synthesis caused by deficiency of
      ovarian steroid hormones in the cerebroneuronal cells of postmenopausal women.

PMID- 10967458
TI  - Anti-inflammatory evaluation of Ficus racemosa Linn. leaf extract.
AB  - The anti-inflammatory activity of Ficus racemosa extract was evaluated on
      carrageenin, serotonin, histamine and dextran-induced rat hind paw oedema models.
      The extract at doses of 200 and 400 mg/kg has been found to possess significant
      anti-inflammatory activity on the tested experimental models. The extract (400
      mg/kg) exhibited maximum anti-inflammatory effect, that is 30.4, 32.2, 33.9 and
      32.0% at the end of 3 h with carrageenin, serotonin, histamine, dextran-induced
      rat paw oedema, respectively. In a chronic test the extract (400 mg/kg) showed
      41.5% reduction in granuloma weight. The effect produced by the extract was
      comparable to that of phenylbutazone, a prototype of a non-steroidal anti
      inflammatory agent.

PMID- 10967459
TI  - Immunomodulatory effect of some naturally occuring sulphur-containing compounds.
AB  - The immunomodulatory effects of naturally occurring sulphur compounds such as
      diallyl sulphide (DAS), diallyl disulphide (DADS) and allyl methyl sulphide (AMS)
      were studied in BALB/c mice. After treatment with five doses (20 mg/dose) of
      sulphur-containing compounds, the total white blood cell (WBC) count was enhanced
      significantly in mice. Among the sulphur compounds studied, DADS showed the
      maximum number of WBC (17,900 cells/mm(3)) on the 6th day, and highest antibody
      titre of 516 on the 12th day. Administration of DAS and DADS enhanced the weight
      of vital organs such as the spleen and thymus. DADS, AMS, and DAS administration
      could enhance the number of plaque forming cells (PFC) in the spleen of the
      animals. Maximum numbers of PFC (1,409 PFC/10(6) spleen cells) were observed in
      DADS-treated animals. Bone-marrow cellularity was also increased significantly
      (P<0.001) in DADS (19.3 x 10(6) cells/femur) and AMS (24.7 x 10(6) cells/femur)
      treated animals. The number of alpha-esterase positive cells was enhanced in DAS
      (1,315/4,000 cells), DADS (1,748/4,000 cells), and AMS (1,648/4,000 cells)
      treated animals, compared to normal animals (1,065/4,000 cells). These results
      are suggestive of an immunostimulating effect of sulphur compounds.

PMID- 10967460
TI  - Herbal medicine in Jordan with special emphasis on less commonly used medicinal
      herbs.
AB  - The use of herbal medicine in Jordan is very common. In order to evaluate the
      knowledge and the attitudes of the herbalists and acquire the common and less
      common medicinal herbs sold by the Jordanian herbalists, more than 100 herbalists
      throughout the country were interviewed and data concerning herbs present in
      their shops, the herbalists' recommendations and other observations were
      collected. The present paper reports on the less common herbs and problems
      observed dealing with them.

PMID- 10967461
TI  - Antifungal activity of volatile constituents of Eugenia dysenterica leaf oil.
AB  - The essential oil from the hydrodistillation of Eugenia dysenterica leaves
      consisted mainly of beta-caryophyllene and alpha-humulene as the major
      sesquiterpene, while limonene and alpha-thujene were the major monoterpene
      hydrocarbons. The main oxygenated mono and sesquiterpene constituents were alpha
      terpineol and beta-caryophyllene oxide, respectively. The oil was investigated
      against eight strains of Candida albicans, 35 strains of Cryptococcus neoformans
      var. neoformans, and two C. neoformans var. gattii isolated from HIV-infected
      individuals with candidosis or cryptococcal meningitis using the agar dilution
      method. Based on the minimal inhibitory concentration (MIC) values, the most
      significant results were obtained against Cryptococcus strains. It was observed
      that 22 strains were inhibited at a concentration of 250 microg/ml, whereas four
      exhibited potent inhibition with MIC values below 125 microg/ml against 10(6)
      UFC/ml organisms. We found MICs > or = 3.12 microg/ml for 91.6, 50 and 30% of all
      Cryptococcus strains in relation of amphotericin B, fluconazole and itraconazole,
      respectively.

PMID- 10967462
TI  - Effect of Indian Hypericum perforatum Linn on animal models of cognitive
      dysfunction.
AB  - The effect of a standardised 50% ethanolic extract of Indian Hypericum perforatum
      (IHp) was investigated for its putative nootropic activity on various
      experimental paradigms of learning and memory, viz. transfer latency (TL) on
      elevated plus-maze, passive avoidance (PA), active avoidance (AA), scopolamine
      and sodium nitrite induced amnesia (SIA & NIA) in albino rats. Pilot studies
      indicated that single dose administration of IHp had little or no acute
      behavioural effects, hence the extract of IHp was administered orally at two dose
      levels (100 and 200 mg/kg, p.o.), once in daily for three consecutive days, while
      piracetam (500/kg, i.p.), a clinically used nootropic agent, was administered
      acutely to rats as the standard drug. Control rats were treated with equal volume
      of vehicle (0.3% carboxymethyl cellulose (CMC)). IHp and piracetam when given
      alone shortened the TL on day 1, 2, 9 and also antagonised the amnesic effects of
      scopolamine and sodium nitrite on the TL significantly. IHp had no significant
      per se effect on the retention of the PA in rats. Only the higher dose (200
      mg/kg, p.o.) produced a significant reversal of scopolamine induced PA retention
      deficit but no significant reversal was observed with sodium nitrite. Piracetam
      showed significant per se facilitatory effect on PA retention and also reversed
      the scopolamine and sodium nitrite induced impaired PA retention. In the AA test,
      IHp in both the doses, and piracetam, facilitated the acquisition and retention
      of AA in rats and the IHp effects were found to be dose dependent. Both the doses
      of IHp and piracetam significantly attenuated the scopolamine and sodium nitrite
      induced impaired retention of AA. These results indicate a possible nootropic
      action of IHp, which was qualitatively comparable with that induced by piracetam.

PMID- 10967463
TI  - Hypoglycemic effect of Equisetum myriochaetum aerial parts on streptozotocin
      diabetic rats.
AB  - The hypoglycemic effect of water as well as butanolic extracts prepared from
      aerial parts of Equisetum myriochaetum (Equisetaceae) was examined in
      streptozotocin induced diabetic rats. A single oral administration of the water
      extract (WE) at doses of 7 and 13 mg/kg and of the butanol extract (BE) at doses
      of 8 and 16 mg/kg significantly (P<0.001) lowered the plasma glucose levels in
      diabetic rats after three hours of the administration. As a reference drug
      glibenclamide was used and showed, at a dose of 3 mg/kg, similar hypoglycemic
      effect like the tested extracts. Three kaempferol glucosides and one caffeoyl
      glucoside were isolated from the drug and were shown to be the main constituents
      in both extracts.

PMID- 10967464
TI  - Hepatoprotective activity of Emblica officinalis and Chyavanaprash.
AB  - Hepatoprotective activity of Emblica officinalis (EO) and Chyavanaprash (CHY)
      extracts were studied using carbon tetrachloride (CCl(4)) induced liver injury
      model in rats. EO and CHY extracts were found to inhibit the hepatotoxicity
      produced by acute and chronic CCl(4) administration as seen from the decreased
      levels of serum and liver lipid peroxides (LPO), glutamate-pyruvate transaminase
      (GPT), and alkaline phosphatase (ALP). Chronic CCl(4) administration was also
      found to produce liver fibrosis as seen from the increased levels of collagen
      hydroxyproline and pathological analysis. EO and CHY extracts were found to
      reduce these elevated levels significantly, indicating that the extract could
      inhibit the induction of fibrosis in rats.

PMID- 10967465
TI  - Polygonum tinctorium extract suppresses nitric oxide production by activated
      macrophages through inhibiting inducible nitric oxide synthase expression.
AB  - Despite its beneficial role in host defense mechanisms, excessive nitric oxide
      (NO) production by activated macrophages has been implicated in several
      inflammatory diseases. To clarify the mechanisms of anti-inflammatory activities
      of Polygonum tinctorium, we evaluated whether extracts of P. tinctorium could
      modulate the production of NO by activated macrophages. An AcOEt extract of P.
      tinctorium markedly inhibited NO synthesis by interferon-gamma (IFN
      gamma)/lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages and the
      macrophage-like cell line RAW 264.7 in a dose-dependent manner. Inhibition of NO
      synthesis was achieved by reducing inducible NO synthase (iNOS) expression at
      protein and mRNA levels. However, the AcOEt extract of P. tinctorium failed to
      inhibit NO synthesis when iNOS was already expressed following stimulation with
      IFN-gamma and LPS. The AcOEt extract also exhibited inhibitory activity on iNOS
      expression in human lung epithelial A549 cells stimulated with a combination of
      IFN-gamma, TNF-alpha and IL-1 beta without affecting the expression of
      constitutive isoforms of NOS. Furthermore, in vivo injection of the AcOEt extract
      of P. tinctorium into LPS-treated mice significantly reduced NO synthesis by
      peritoneal exudate cells under ex vivo conditions. These results suggest that P.
      tinctorium extract may be a potential therapeutic modulator of NO synthesis in
      various pathological conditions.

PMID- 10967466
TI  - Antitumor activity of methanolic extract of Cassia fistula L. seed against
      Ehrlich ascites carcinoma.
AB  - Effects of methanolic extract (ME) of Cassia fistula seed on the growth of
      Ehrlich ascites carcinoma (EAC) and on the life span of tumor bearing mice were
      studied. ME treatment showed an increase of life span, and a decrease in the
      tumor volume and viable tumor cell count in the EAC tumor hosts. Cytological
      studies have revealed a reduction in the mitotic activity, and the appearance of
      membrane blebbing and intracytoplasmic vacuoles in the treated tumor cells.
      Improvement in the hematological parameters following ME treatment, like
      hemoglobin content, red blood cell count and bone marrow cell count of the tumor
      bearing mice have also been observed. The results of the present study suggest
      that ME of C. fistula seed has an antitumor activity.

PMID- 10967467
TI  - Antithrombin activity of medicinal plants of the Azores.
AB  - A chromogenic bioassay was utilized to determine the antithrombin activity of
      methylene chloride and methanol extracts prepared from 50 plants of Azores.
      Extracts of the six plants Hedychium gardneranum, Tropaeolum majus, Gunnera
      tinctoria, Hedera helix, Festuca jubata and Laurus azorica demonstrated activity
      of 78% or higher in this bioassay system.

PMID- 10967469
TI  - Free radical scavenging activity of Lafoensia pacari.
AB  - The methanolic extract of the stem bark of Lafoensia pacari (Lythraceae) showed
      free radical scavenging activity in the diphenyl picryl hydrazyl radical (DPPH)
      decoloration assay and inhibited the enzyme xanthine oxidase 'in vitro'. Bioassay
      guided isolation led to ellagic acid (EA) as the main active compound of
      Brazilian and Paraguayan collections of the plant.

PMID- 10967468
TI  - Evaluation of the immunomodulatory effects of five herbal plants.
AB  - A group of medicinal plants including, Silybum marianum, Matricaria chamomilla,
      Calendula officinalis, Cichorium intybus and Dracocephalum kotschyi which grow in
      Iran, were extracted with ethanol 70% and the mitogenic activity was examined
      both on human peripheral blood lymphocytes and thymocytes. Effect of these
      extracts on proliferative responsiveness of human lymphocytes to
      phytohemagglutinin (PHA) and on the mixed lymphocyte reaction (MLR) was also
      investigated. The results obtained indicated that none of the extracts had a
      direct mitogenic effect on human lymphocytes or thymocytes (stimulation index,
      SI<0.07). Among the plants studied, C. intybus and C. officinalis showed a
      complete inhibitory effect on the proliferation of lymphocytes in the presence of
      PHA (SI range 0.01-0.49). A dose dependent inhibitory effect was obtained in the
      case of D. kotschyi. Extract of M. chamomilla showed almost no stimulatory
      effect. A significant decrease in proliferation assay due to 0.1-10 microg/ml of
      S. marianum was observed (SI<0.46, P<0.05). In MLR, a markedly stimulatory effect
      with some lower concentrations of all the extracts except Dracocephalum was
      detected. The highest stimulatory effect was due to 100 microg/ml of S. marianum
      (SI 2.82). Treatment of mixed lymphocytes with 0.1-10 microg/ml of C. officinalis
      (SI range 1.34-1.80) and 10 microg/ml of M. chamomilla and C. intybus (SI 2.18
      and 1.70, respectively) strongly increased the cell proliferation. In conclusion,
      this in vitro study revealed the capacity of all the extracts except
      Dracocephalum to enhance the proliferation of lymphocytes after stimulation with
      the allogenic cells.

PMID- 10967470
TI  - Assessment of the effect of Maytenus ilicifolia (espinheira santa) extract on the
      labeling of red blood cells and plasma proteins with technetium-99m.
AB  - We are trying to develop a model to assess properties of products utilized in
      popular medicine. Maytenus ilicifolia is used in herbal medicine. Red blood cells
      (RBC) labeled with technetium-99m (99mTc) are employed in nuclear medicine. This
      labeling procedure depends on a reducing agent and stannous chloride is used.
      There is evidence that this labeling may be altered by drugs. We have
      investigated the possibility of M. ilicifolia extract being capable to alter the
      labeling of blood elements with 99mTc. Blood was incubated with M. ilicifolia
      extract. Stannous chloride solution and Tc-99m were added. Blood was centrifuged
      and plasma (P) and blood cells (C) were isolated. Samples of P or C were also
      precipitated, centrifuged and insoluble (IF) and soluble (SF) were separated. The
      percentages of radioactivity (%ATI) in C, IF-P and IF-C was calculated. The %ATI
      decreased on C from 93.6+/-2.3 to 29.0+/-2.7, on IF-P from 77.6+/-1.2 to 7.5+/
      1.0 and on IF-C from 80.0+/-3.4 to 12.6+/-4.8. Once in RBC labeling procedure
      with 99mTc depends on the presence of stannous (+2) ions, the substances of the
      M. ilicifolia extract could increase the valence these ions to stannic (+4). This
      fact would decrease the %ATI on blood elements and indicate the presence of
      oxidant agents in the M. ilicifolia extract.

PMID- 10967471
TI  - Insecticidal activity against Aedes aegypti larvae of some medicinal South
      American plants.
AB  - The insecticidal activity of 11 extracts from nine South American medicinal
      plants has been studied using the Aedes aegypti larvicidal assay. Eight of the 11
      plant extracts studied showed toxicity against the A. aegypti larvae (LC(50)<500
      microg/ml). The dichloromethane extracts of Abuta grandifolia and Minthostachys
      setosa demonstrated high larvicidal activity, the most active being the
      dichloromethane extract of A. grandifolia, with an LC(50)=2.6 microg/ml (LC(100)=
      8.1 microg/ml), indicating an activity 2-fold higher than beta-asarone, a natural
      botanical insecticide used as a positive control (LC(100)=16 microg/ml). On the
      other hand, the dichloromethane extract of M. setosa was quite potent against A.
      aegypti larvae showing an LC(50)=9.2 microg/ml (LC(100)=25.2 microg/ml). The
      results obtained suggest that the extracts of A. grandifolia and M. setosa are
      promising as larvicides against A. aegypti larvae and could be useful in the
      search for new larvicidal natural compounds.

PMID- 10967472
TI  - Ethnopharmacological survey of traditional drugs sold in Israel at the end of the
      20th century.
AB  - This report deals with the results of a study of present day uses of traditional
      medicinal materials in Israel. The survey covered selected markets in medicinal
      materials, belonging to various religious and ethnic communities, and also
      included questioning of the sellers and buyers about the healing characteristics
      of the various materials. The survey yielded information on many and varied
      medicinal materials, of which 310 are identified according to the following
      classifications, 264 species of plants (85.1%); 20 species of animals (6.5%); 19
      kinds of minerals (6.5%); and seven materials of other or mixed origin (2.3%).
      Analysis of the data showed that a significant proportion of the materials were
      of local origin (51.5%) and some were imported from other countries. These data
      demonstrate that there is still a flourishing and well developed trade in these
      materials - a trade which is the remnant of a rich and ancient medical culture,
      which is disappearing from the modern world.

PMID- 10967473
TI  - Pharmacological effects of the aqueous extract of Neorautanenia mitis in rodents.
AB  - The pharmacological effects of the aqueous extract of Neorautanenia mitis (family
      Papilonaceae) were studied in rodents. Investigations were carried out on acetic
      acid-induced writhing (pain) in mice and hind paw oedema in rats. The effects of
      the extract were also studied on the isolated non-pregnant rat uterus and rabbit
      jejunum. Results showed the extract to possess significant (P<0.05) dose
      dependent anti-nociceptive activity between 12.5 and 50.0 mg/kg p.o. in mice and
      slight anti-inflammatory activity at 25 and 50 mg/kg p.o. in rats. The extract
      also produced a concentration-dependent inhibition of the normal rhythmic
      contraction of the isolated non-pregnant rat uterus. It was found to inhibit
      oxytocin-induced as well as acetylcholine-induced contractions in the rat uterus.
      The extract also exhibited concentration-dependent inhibition of spontaneous
      contractions of the rabbit jejunum. Preliminary phytochemical analysis of the
      extract revealed the presence of saponin glycosides, flavonoids, tannins and
      alkaloids. The extract had an intraperitoneal (i.p.) LD(50) of 282.84+/-3.2 mg/kg
      in mice. These data corroborate the traditional use of this plant in the
      treatment of dysmenorrhea.

PMID- 10967474
TI  - Fetotoxic potentials of Globularia arabica and Globularia alypum (Globulariaceae)
      in rats.
AB  - Adult female Sprague-Dawley rats received by intragastric application, ethanolic
      extracts of Globularia arabica and Globularia alypum dried leaves. The effect of
      the extracts was monitored on fertility. The ingestion by female rats of 800
      mg/kg of ethanolic extracts of G. arabica and G. alypum, from day 1 to day 6 of
      pregnancy, did not cause pregnancy failure. However, the ingestion of ethanolic
      extracts of G. alypum significantly reduced the number of viable fetuses. The
      number of resorptions was significantly increased in pregnant females
      administered ethanolic extracts of both G. arabica and G. alypum. The ingestion
      of 800 mg/kg of ethnologic extracts of G. arabica and G. alypum for 30
      consecutive days by adult female rats had no significant effect on the occurrence
      of pregnancy. However, the ingestion of extracts of both species increased the
      number of resorptions and only G. alypum extract caused a significant reduction
      in the number of viable fetuses. These results indicate that ingestion of G.
      arabica and G. alypum could have some reproductive toxicity in female rats.

PMID- 10967475
TI  - Antiherpetic activities of acidic protein bound polysacchride isolated from
      Ganoderma lucidum alone and in combinations with acyclovir and vidarabine.
AB  - To investigate antiherpetic activity, an acidic protein bound polysaccharide
      (APBP) was isolated from carpophores of Ganoderma lucidum. This brownish APBP was
      isolated from water soluble substances of the carpophores by activity-guided
      isolation method. APBP was tested for its antiviral activity against herpes
      simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay in
      tissue culture. APBP showed potent antiviral activity against HSV-1 and HSV-2 in
      Vero cells at its 50% effective concentration (EC(50)) of 300 and 440 microg/ml,
      respectively. APBP had no cytotoxicity on Vero cells at a concentration of 1 x
      10(4) microg/ml. APBP exhibited a potent antiviral activity with selectivity
      index (SI) of more than 22.73. The combined antiherpetic effects of APBP with
      nucleoside antiherpetic agents, acyclovir (ACV) and vidarabine (ara-A), were
      examined on the multiplication of these two strains of herpesviruses in Vero
      cells by the combination assay. The results of combination assay were evaluated
      by the combination index (CI) that was calculated by the multiple drug effect
      analysis. CI values were in the range 0.47-0.51 for a combination of APBP with
      ACV, and in the range of 1.02-1.18 for a combination of APBP with ara-A. The
      combinations of APBP with ACV on HSV-1 and HSV-2 showed potent synergistic
      effects, and these results suggest that the possibility of developing APBP as a
      new antiherpetic agent.

PMID- 10967476
TI  - Antinociceptive properties of extracts of new species of plants of the genus
      Phyllanthus (Euphorbiaceae).
AB  - The hydroalcoholic extract (HE) of the four new species of Phyllanthus, given
      intraperitoneally, produced significant inhibition of acetic acid-induced
      abdominal constrictions, with mean ID(50) values of 0.3, 1.8, 7.4 and 26.5 mg/kg
      for Phyllanthus amarus, Phyllanthus orbiculatus, Phyllanthus fraternus and
      Phyllanthus stipulatus, respectively. In the formalin test, the four species of
      Phyllanthus, also produced graded inhibition against both phases of formalin
      induced licking, being more active in relation of the late phase. The HE of the
      Phyllanthus species elicited significant inhibition of the capsaicin-induced
      neurogenic pain, with mean ID(50) values of 8.9, 6.7, >30 and approximately 30
      mg/kg for P. amarus, P. fraternus, P. stipulatus and P. orbiculatus,
      respectively. Given orally all HE of the Phyllanthus species were less potent and
      efficacious than when given by intraperitoneally. Results of the present study
      extend previous data and indicate that all extracts of Phyllanthus plants so far
      studied exhibit pronounced antinociception when assessed in chemical models of
      nociception, namely acetic acid-induced writhing, and formalin and capsaicin
      induced licking.

PMID- 10967477
TI  - Cytotoxic, hepatoprotective and free radical scavenging effects of propolis from
      Brazil, Peru, the Netherlands and China.
AB  - Propolis is a resinous hive product collected by honeybees from various plant
      sources. The composition of the propolis depends upon the time, vegetation and
      the area of collection. Thus, quality evaluation of the propolis is important,
      before use in food and beverages. For this propose three different biological
      activities were carried out, i.e. 1,1-diphenyl-2-picrylhydrazyl (DPPH) free
      radical scavenging activity, cytotoxicity and hepatoprotective activity, of MeOH
      and water extracts of nine different propolis from Brazil, Peru, the Netherlands
      and China. The results showed that water extracts of six Brazilian and a Chinese
      propolis possessed stronger DPPH free radical scavenging activity than the
      corresponding MeOH extract, whereas in the case of Netherlands and Peruvian
      propolis MeOH extract exhibited stronger DPPH free radical scavenging activity.
      The MeOH extracts of all propolis possessed stronger cytotoxicity than the
      corresponding water extract towards murine colon 26-L5 carcinoma and human HT
      1080 fibrosarcoma cells. The result of hepatoprotective activity of Brazilian
      propolis on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)
      induced cell death in primary cultured mouse hepatocytes were found in accordance
      with the grade set up by beekeepers in Brazil.

PMID- 10967478
TI  - Antibacterial, anthelmintic and anti-amoebic activity in South African medicinal
      plants.
AB  - Hexane, ethanol and water extracts of plants used by South African traditional
      healers for treating stomach ailments were screened for antibacterial,
      anthelmintic and anti-amoebic activities. To evaluate antibacterial activity, the
      disc-diffusion assay was used against several Gram-positive and Gram-negative
      species. Minimal inhibitory concentration values were determined with a
      microdilution assay. Ethanolic extracts showed the greatest activity, and Gram
      positive bacteria were the most susceptible microorganisms. The free-living
      nematode Caenorhabditis elegans was used in two different assays to evaluate
      anthelmintic activity. A microdilution technique was employed to investigate anti
      amoebic activity against the enteropathogenic Entamoeba histolytica. These assays
      were suitable for the screening of a large number of extracts at one time.
      Several plants exhibited significant activity against these test organisms.

PMID- 10967479
TI  - Preliminary studies on the anti-inflammatory and analgesic activity of the
      methanolic fraction of the root extract of Tragia involucrata Linn.
AB  - Tragia involucrata has been widely used in the traditional medicinal system for
      the treatment of a variety of diseases. The effect of methanolic extract of T.
      involucrata was studied in different experimental animal models and it was
      revealed that the extract possesses significant analgesic and anti-inflammatory
      activity.

PMID- 10967480
TI  - In vitro purgative effect of Ruellia praetermissa. Sceinf.ex.Lindau
      (Acanthaceae).
AB  - Methanol, ethylacetate and aqueous extracts of Ruellia praetermissa initiated
      spontaneous contractions in the quiescent and increased contraction on the
      electrically stimulated ileal strip at a concentration of 30 microg/ml. The
      extracts produced concentration-related contractions both in amplitude and tone
      up till 750 microg/ml with IC(50) of 360 microg/ml (methanol extract), 425
      microg/ml (ethylacetate extract) and 540 microg/ml (aqueous extract).
      Acetylcholine also produced a concentration-related (IC(50)=18 microg/ml)
      contractions of the isolated ileum. Atropine in concentrations of 3.4 x 10(-6)-3
      x 10(-3) microg/ml antagonized progressively the response of the isolated ileum
      to acetylcholine (32 x 10(-2) microg/ml) and the methanol extract (650 microg/ml)
      induced contractions suggesting a mode of action via cholinergic system. Luteolin
      and apigenin and iridoid glucosides (taxiphilin and 8-epi-deoyganic acid) might
      be responsible at least in part for the observed effect.

PMID- 10967481
TI  - Anti-inflammatory, analgesic activity and acute toxicity of Sida cordifolia L.
      (Malva-branca).
AB  - Sida cordifolia L. (Malvaceae) is used in folk medicine for the treatment of
      inflammation of the oral mucosa, blenorrhea, asthmatic bronchitis and nasal
      congestion. The anti-inflammatory, analgesic effects and acute toxicity of an
      aqueous extract of S. cordifolia were evaluated in animal models. The extract was
      prepared using leaves collected before the flowering period. The aqueous extract
      (AE) showed a significant inhibition of carrageenin-induced rat paw edema at a
      dose of 400 mg/kg administered orally, but did not block the edema induced by
      arachidonic acid. The AE also increased the latency period for mice in the hot
      plate test, and inhibited the number of writhes produced by acetic acid at the
      oral dose of 400 mg/kg. The aqueous extract of S. cordifolia showed low acute
      toxicity in mice.

PMID- 10967482
TI  - Folk medicinal use of some animal products in Central Sudan.

PMID- 10967483
TI  - The effect of Plantago ovata on humoral immune responses in experimental animals.
AB  - The effect of the aqueous extract of Plantago ovata (PO) (Plantaginaceae)
      consisting of a mixture of polysaccharides and glycoside on humoral immune
      responses was studied. In rabbits, after oral administration of PO (0.5 g/kg) a
      significant decrease in anti-HD antibody titre was observed in primary response.
      Intraperitoneal injection of 0.25 g/kg of PO in mice prior to immunisation with
      sheep red blood cells (SRBC) resulted in a significant decrease in
      hemagglutinating antibody (HD) titre. Oral administration and intraperitoneal
      injection of 0.25 and 0.5 g/kg of PO resulted in a significant increase in white
      blood cells (WBC) and spleen leukocytes counts. The spleen weight also increased
      with intraperitoneal injection (0.25 and 0.5 g/kg) and oral administration of 0.5
      g/kg of PO. Present results indicate that PO can suppress the humoral immune
      responses, especially in primary immune response.

PMID- 10967484
TI  - Antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit
      extract.
AB  - In this study, probable antinociceptive and anti-inflammatory effects of
      Elaeagnus angustifolia fruit components, were evaluated. For evaluation of
      antinociceptive effects, the chronic (formalin test) and acute (tail-flick) pain
      models of rats were used. For the anti-inflammatory effects, the paw inflammation
      model was used through subcutaneous injection of 5% formalin to the paw of male
      rats. Water extracts of the fruit and its components in the single dose were
      assessed through comparison with the antinociceptive and anti-inflammatory
      effects of sodium salicylate (SS) as a positive control. Administration of 300
      mg/kg of SS (i.p.) had no effect on tail flick latency, while 1000 mg/kg of total
      (i.p. and p.o.) and endocarp (i.p.) extract, increased this latency (P<0.01,
      P<0.001, respectively), which was not reversed by naloxone (2 mg/kg). In the
      formalin test, SS (300 mg/kg, i.p.) and the extract (1000 mg/kg, p.o. )
      alleviated the animals nociception in the second phase, while in the first phase
      they were not effective. The total and endocarp extracts (1000 mg/kg, i.p.)
      showed a significant effect on both phases (P<0.01, P<0.001, respectively) which
      was also not reversed by naloxone (2 mg/kg, i.p.). In the acute anti-inflammatory
      test, the total extract and the aqueous extract of individual fruit components
      showed a significant effect (P<0.001). This anti-inflammatory effect was not
      significant compared with the anti-inflammatory effect of SS. Because of the
      extract effect on the tail-flick latency and both phases of the formalin test,
      the site of its analgesic action is probably central, and the mechanism of
      antinociceptive action of the extract are not related to the opioid system. Our
      phytochemical studies indicated that aqueous extract of E. angustifolia fruit
      contains flavonoids, terpenoids and cardiac glycosides.

PMID- 10967485
TI  - Oral hypoglycaemic activity of Ipomoea aquatica.
AB  - Ipomoea aquatica is a commonly consumed green leafy vegetable in Sri Lanka which
      is supposed to possess an insulin-like activity [Jayaweera, D.M.A., 1982.
      Medicinal Plants (Indigenous and Exotic) Used in Ceylon. Part 11. National
      Science Council, Colombo, Sri Lanka, pp. 99]. Only a little attention has been
      paid to the therapeutic use of this plant. We studied the oral hypoglycaemic
      activity of single and multiple doses of I. aquatica in healthy, male Wistar rats
      after a glucose challenge. There was a significant reduction in the serum glucose
      concentrations with both single (33%, P<0.0027) and multiple (25%, P<0.02) doses.
      The optimum dose was 3.4 g/kg while the optimum activity was given 2 h after the
      administration of the extract. The present study indicates that a boiled, whole
      extract of I. aquatica exerts an oral hypoglycaemic effect in healthy, male,
      Wistar rats after a glucose challenge.

PMID- 10967486
TI  - Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in
      rats.
AB  - The present work was done to investigate the possible effects of Nigella sativa
      oil (NSO) on gastric secretion and ethanol-induced ulcer in rats. Thirty two
      adult male rats were used in this study (four groups) and several parameters were
      determined to assess any degree of protection. It was found that the
      administration of NSO in rats produced a significant increase in mucin content
      and glutathione level and a significant decrease in mucosal histamine content.
      Ethanol administration produced a 100% ulcer induction with an ulcer score of
      12.62+/-1.35 (mean+/-S.E., n=8). It caused a significant reduction in free
      acidity and glutathione level while it produced a significant increase in mucosal
      histamine content. When animals were pretreated with NSO before induction of
      ulcer, there was a significant increase in glutathione level, mucin content and
      free acidity and a significant decrease in gastric mucosal histamine content with
      a protection ratio of 53.56% as compared to the ethanol group. It can be
      concluded that NSO imparted a protective action against ethanol induced ulcer in
      rats.

PMID- 10967487
TI  - Pediculocidal and scabicidal properties of Lippia multiflora essential oil.
AB  - The essential oil from the leaves of Lippia multiflora Moldenke (Verbenaceae) was
      tested for its pediculocidal and scabicidal activites against bodylice, headlice
      and scabies' mites. The 'knockdown' times obtained for bodylice and headlice
      using lippia oil preparations were comparatively shorter than those obtained
      using benzyl benzoate and Delvap Super, a brand of dichlorvos. The lethal effect
      of the lippia oil on headlice was increased when applied in an enclosed system
      that prevented volatilization of the oil while allowing maximum contact of the
      vapour with the headlice. A 20% v/v preparation of lippia oil applied to
      scabietic subjects for 5 consecutive days gave 100% cure compared with 87.5% cure
      obtained for benzyl benzoate preparation of the same concentration. The GC-MS
      analysis of oil revealed, among others, the presence of terpineol, alpha- and
      beta-pinene which are known to be lethal to body and headlice.

PMID- 10967488
TI  - Antibacterial activity of water and acetone extracts of the roots of Euclea
      natalensis.
AB  - Water and acetone extracts of the roots of Euclea natalensis A.DC. were
      investigated for their in vitro antibacterial properties. The Gram-positive
      bacteria tested appeared to be more susceptible to the extracts than the Gram
      negative bacteria. The water and acetone extracts inhibited the growth of
      Bacillus cereus, Bacillus pumilus, Bacillus subtilis, Micrococcus kristinae and
      Staphylococcus aureus at concentrations ranging between 0.1 and 6.0 mg/ml. The
      water extract did not exert any inhibitory action on Gram-negative bacteria while
      the acetone extract showed inhibitory activity at a concentration of 5.0 mg/ml
      against all the Gram-negative bacteria investigated. The antibacterial activity
      of acetone extract was also investigated by a direct bioassay on TLC plates
      against S. aureus.

PMID- 10967489
TI  - Evaluation of the antiviral activity of an aqueous extract from Phyllanthus
      orbicularis.
AB  - The antiviral and cytotoxic activity of Phyllanthus orbicularis, a member of the
      Euphorbiaceae, was evaluated in tissue culture. An aqueous extract made from
      leaves and stems of this plant exhibited selective antiviral indexes of 12.3 and
      26 against bovine herpesvirus type 1 and herpes simplex virus type 2,
      respectively, showing no selective antiviral activity against adenovirus type 5
      and mengovirus. Incubation with this plant extract during cell culture infection,
      impaired the productive replication of both herpes viruses in an extract
      concentration-dependent manner, also depending on the multiplicity of infection
      (MOI) used. The results obtained suggested that the P. orbicularis antiviral
      activity might be partially due to a direct interaction with virus particles or
      their entry into the cell, instead of interfering with intracellular virus
      specific macromolecular synthesis.

PMID- 10967490
TI  - Studies on the vascular effects of the fractions and phenolic compounds isolated
      from Viscum album ssp. album.
AB  - Viscum album L. has been used in the indigenous system of medicine for treatment
      of various diseases such as atherosclerosis and hypertension. In the literature,
      phenylpropan and flavonoid derivatives were suggested to play a role in the
      inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and a
      correlation was proposed between the in vitro inhibition of PDE and in vivo
      pharmacological activity. The vascular effects of the phenolic compounds and
      subfractions isolated from n-butanolic fraction of V. album ssp. album were
      studied on noradrenaline-contracted rat aortic rings. Isolated phenolic compounds
      (Syringin (VA-1), Coniferin (VA-9), 5, 7-dimethoxy-flavanone-4'-O-[beta-D
      apiofuranosyl(1-->2)]-beta-D-gl uco pyranoside (VA-4)) produced concentration
      dependent contractions in rat aortic rings. Only one compound (Kalopanaxin D (VA
      15)) displayed very slight relaxant response. The weak concentration-dependent
      relaxing effect of the subfractions gave the idea that vasodilator activity were
      observed in the less polar subfractions. In addition, there was no clear
      correlation between the weak relaxant effects of subfractions and an inhibitory
      effect on cAMP-PDE.

PMID- 10967491
TI  - Effects of Momordica charantia powder on serum glucose levels and various lipid
      parameters in rats fed with cholesterol-free and cholesterol-enriched diets.
AB  - The effects of dietary bitter melon (Momordica charantia) freeze-dried powder on
      serum glucose level and lipid parameters of the serum and liver were studied in
      rats fed diets supplemented with and without cholesterol. Rats were fed the diets
      for 14 days containing bitter melon freeze-dried powder at the level of 0.5, 1
      and 3% without an added dietary cholesterol (experiment I) and those containing
      bitter melon at the level of 1% with or without 0.5% cholesterol and 0.15% bile
      acid (experiment II). No adverse effect of dietary bitter melon powder on growth
      parameters and relative liver weight were noted. Dietary bitter melon resulted in
      a consistent decrease in serum glucose levels in rats fed cholesterol-free diets,
      but not in those fed cholesterol-enriched diets, although no dose-response was
      noted. Addition of cholesterol to the diets as compared to those without added
      cholesterol caused hypercholesterolemia and fatty liver. Bitter melon had little
      effect on serum lipid parameters, except for high density lipoprotein (HDL)
      cholesterol; HDL-cholesterol levels tended to decrease by dietary cholesterol,
      while they were consistently elevated by dietary bitter melon both in the
      presence and absence of dietary cholesterol, indicating an antiatherogenic
      activity of bitter melon. In addition, bitter melon exhibited a marked reduction
      in the hepatic total cholesterol and triglyceride levels both in the presence and
      absence of dietary cholesterol; the reduction of triglyceride levels in the
      absence of dietary cholesterol was in a dose-dependent manner. These results
      suggest that bitter melon can be used as a health food.

PMID- 10967492
TI  - Effects of Teucrium divaricatum Heldr. ssp. divaricatum decoction on experimental
      ulcer in rats.
AB  - The effects of chronic intragastric administration of the aerial parts decoction
      of Teucrium divaricatum Heldr. ssp. divaricatum (Labiateae) on experimental
      acetylsalicylic acid (ASA)-induced ulcer were studied in rats. The ulcer index
      and histological mucosa regeneration were evaluated. The ulcer index
      significantly decreased (U.I. 1.7+/-1.5; P<0.05) after treatment with a
      lyophilized decoction of T. divaricatum (500 mg/kg os), once daily for 7 days,
      compared to the control (U.I. 11.4+/-2.3). The ultrastructure modifications of
      gastric mucosa were observed by transmission electronic microscopy (TEM)
      confirming the antisecretory effect exercised by administration of the T.
      divaricatum decoction. Treatment with T. divaricatum seems to block up parietal
      cell acid secretion and to stimulate in the chief cells the formation of zymogen
      granules.

PMID- 10967493
TI  - Preface.

PMID- 10967494
TI  - Proliferation of endothelial cells on the plasma-treated segmented-polyurethane
      surface: attempt of construction of a small caliber hybrid vascular graft and
      antithrombogenicity.
AB  - To prepare a porous segmented-polyurethane (SPU) tube, a solution of SPU
      containing different concentrations of NaCl was coated on a glass rod and the
      coated SPU was immediately immersed in water. When the surface of the porous SPU,
      where bovine aortic endothelial cells are not normally capable of adhering and
      proliferating, was modified by plasma treatment, the proliferation of endothelial
      cells could be drastically improved. The cells proliferated confluently on the
      porous SPU surface prepared at low concentrations of NaCl below 10 g per 100 ml,
      but poorly on the porous surface prepared at high concentrations of NaCl. The
      construction of a hybrid vascular graft consisting of a porous SPU tube (2 mm in
      inner diameter, 5 cm in length) and endothelial cells was attempted. The cells
      cultured on the inner surface of the tube proliferated to confluency everywhere.
      From an in vitro antithrombogenic evaluation test, which involved the use of
      human blood, the present hybrid graft can be considered to provide an inert
      surface against thrombus formation and blood coagulation. Negligible changes in
      shape of human leukocytes in contact with bovine aortic endothelial cell surface
      occurred, suggesting that the bovine aortic endothelial cells used are
      immunologically less active against human blood.

PMID- 10967495
TI  - Antithrombogenicity of cultured endothelial cell-detached surface.
AB  - To examine the antithrombogenicity of cultured endothelial cell-detached surface,
      a simple hybrid vascular model tube consisting of a glass tube and endothelial
      cells was constructed. To detach the endothelial cells from the inner surface of
      the model tube, a steady shear stress of 2 or 8 N m(-2) was imposed onto the
      surface of endothelial cell monolayer by means of a coaxial double cylinder
      rotational-type apparatus. Coagulation of blood in contact with the endothelial
      cell-detached surface was examined using a damped oscillation rheometer.
      Coagulation of whole blood in the cell-detached tube occurred at about 40 min,
      which was almost the same as that in the endothelial cell-coated tube. A few
      platelets without shape change adhered to the endothelial cell-detached surface.
      These data suggest that the endothelial cell-detached surface may exhibit
      antithrombogenic and anticoagulant surfaces. Biochemical analyses showed that the
      glass surface, where endothelial cell was detached, was covered with components
      such as collagen type IV that is considered to be produced from the endothelial
      cells on the glass surface.

PMID- 10967496
TI  - Ion implantation into collagen-coated surfaces for the development of small
      diameter artificial grafts.
AB  - Ion implantation into collagen (Type I) coated inner surfaces of test tubes with
      a length of 50 mm and an inner diameter of 2 and 3 mm were performed to develop
      hybrid type small diameter artificial vascular grafts. To obtain information
      about the cellular response and chemical and physical structure of those collagen
      surfaces, several experiments such as platelets adhesion test, endothelial cell
      culture, analysis of amino acids and animal study were performed. He(+) ion
      implanted collagen coated specimen exhibited cell attachment and inhibit platelet
      adhesion. From these results, it was assumed that He(+) ions broke the ligands
      that correspond to platelet, and the ligands that correspond to endothelial cell
      adhesion still existed after ion implantation. It was suggested that platelets
      and cell attachment could be control individually by ion implantation into
      collagen.

PMID- 10967497
TI  - Oxygen ion implantation at 20 to 2000 keV into polysulfone for improvement of
      endothelial cell adhesion.
AB  - The irradiation effects of oxygen on polysulfone have been investigated at
      energies of 20 keV, 150 keV and 2 MeV. The strong improvement of endothelial cell
      adhesion and proliferation is found on ion irradiated polysulfone at 20 keV. Such
      improvement is declined with increasing ion energy. The changes of surface color
      and free energy are strongly dependent on ion energy and dose. The formation of
      amorphous carbon phase is demonstrated by Raman spectroscopy and its degree is
      correspondent to the color changes observed. The formations of hydroxyl and
      carboxyl groups are confirmed by the attenuated total reflectance (ATR) FTIR
      spectroscopy. The depletions of heteroatoms are conjectured by detail analysis of
      X-ray photoelectron spectroscopy (XPS). Since no single one of these changes can
      be related directly to the improved adhesion and proliferation of endothelial
      cells on irradiated surface, we argue that the distribution of functional groups
      is crucial in promoting the adhesion of endothelial cells. Although the
      distribution cannot directly be detected at present, the irradiation effects were
      related to the results of TRIM simulation. The surface changes can be controlled
      by adjusting the size energy and dose of irradiating ion for the optimum
      morphology to cell adhesion.

PMID- 10967498
TI  - Chemical changes of polymeric surfaces after modification with multi-source
      cluster deposition.
AB  - A new process for surface modification of polymers with multi-source cluster
      deposition apparatus has been reported in our previous work. The apparatus
      simultaneously supplies reactant of ammonium sulfamate and activator of energetic
      Ar(+) ion. In this work chemical changes are analyzed on the basis of XPS spectra
      and the relations of contact angle and platelet adhesion with chemical changes
      are discussed. Polymer film, setting on a turning holder, was irradiated by Ar(+)
      ions during bombardment with ammonium sulfamate clusters. The Ar(+) ion source
      served for activation of polymer surface and a cluster ion source supplied
      ammonium sulfamate molecules to react with activated surface. After thorough
      washing with deionized sterile water, the modified surfaces were evaluated in
      terms of contact angle of water, elemental composition and binding state on XPS
      and platelet adhesion with platelet rich plasma (PRP). The modification of
      polysulfone decreased the contact angle of water on surfaces from 82.6 down to
      34.5 degrees. The adhesion number of platelets were decreased to one-tenth of the
      original surface. Ammonium, amine, sulfate and thiophene combinations were formed
      on the modified surfaces. The primary studies showed successful modification of
      polysulfone with ammonium sulfamate by assistance of Ar(+) ion irradiation. The
      polar groups like N-sulfate were formed on surfaces and contribute to the
      decrease of surface contact angle and adhesion number of platelets. Since the
      same process can also be applied to other polymeric materials with various
      substrates, combining with the features of no solvent and no topographic changes,
      this method might be developed in a promising way for modification of polymers.

PMID- 10967499
TI  - Ultra-hydrophobic fluorine polymer by Ar-ion bombardment.
AB  - A study has been made of the improvement of the hydrophobicity of a fluorine
      polymer (polytetra-fluorinethylene, PTFE) by Ar-ion bombardment. Ar-ion
      bombardment to PTFE) by Ar-ion bombardment. Ar-ion bombardment to PTFE sheets was
      carried out at the fluences ranging from 3.1x10(20) to 18.3x10(20) ions/m(2). The
      beam current densities were ranged from 1.25 to 7.5 A/m(2). The hydrophobicity of
      modified materials has been investigated by means of a sessile drop method of
      water. The roughness, morphology and structure of bombarded specimens have been
      estimated as a function of beam current density and acceleration energy. It was
      found that Ar-bombardment causes the contact angle of water to increase from the
      original value 103 to 170 degrees. The results indicate that Ar-bombardment at an
      optional condition results in the formation of ultrahydrdophobic surfaces. The
      effects of Ar-bombardment to hydrophobicity of PTFE are discussed with the
      relationship among roughness, morphology and chemical bonding states of the
      surfaces.

PMID- 10967500
TI  - Surface hardness changes induced by O-, Ca- or P-ion implantation into titanium.
AB  - Titanium or titanium alloys are very attractive biomedical materials.
      Biocompatible elements of oxygen, calcium and phosphorus were implanted into
      titanium and changes of surface hardness were measured using an ultra micro
      indenter (UMIS-2000). A multiple load-partial unload procedure that can reveal a
      hardness versus depth profile was adopted. Depth profiles of concentration of
      implanted ions were obtained by SIMS measurement. For O and P implantation, it is
      observed that the hardness increases with the increases in the dose. O
      implantation produced the largest increase in hardness, up to 2.2 times higher
      than the unimplanted titanium. On the other hand, Ca implantation produced only a
      small increase in the hardness that was independent of the ion dose. The surface
      oxide layer of a Ca implanted titanium sample was much thicker than the
      unimplanted samples or those implanted with O and P ions. The depth of maximum
      hardness increases with increasing energy of implanted ions. The depths of the
      maximum hardness occur at indentation depths of one-third to one-eighth of the
      mean ranges of implanted ions.

PMID- 10967501
TI  - Crystallization in low-energy deposition of titanium ions.
AB  - To investigate crystallization in the ion beam deposition process, titanium ions
      were deposited on silicon wafers at 105 and 55 eV. As titanium is an active
      metal, titanium compounds are formed by absorbing backfilled or residual gas. At
      energy levels of 105 or 55 eV, titanium crystallizes in a NaCl-type titanium
      compound with the backfilling of air. In all samples, (110)-oriented crystals
      grew with a rectangular lattice arrangement of titanium atoms. The open channel
      <110> of preferentially oriented crystal growth was parallel to the direction of
      incident ions normal to the substrate surface.

PMID- 10967502
TI  - Absorption in the visible region of YSZ implanted with Ag ions.
AB  - Ag ions were implanted into YSZ (yttrium-stabilized (cubic) zirconia) single
      crystals in two different energy regimes: kiloelectron volt and megaelectron
      volt. Optical absorption spectra were measured in the visible region at each
      stage in the annealing process of the sample. Depth profiles of Ag for the
      samples implanted at the energy of 20 keV were measured by X-ray photoelectron
      spectroscopy (XPS). For the samples implanted with Ag at the low energy of 20
      keV, one large absorption peak appeared in the wavelength ranging from 470 to 536
      nm, depending on the dose of Ag ions. As the sample was heated to 1000 degrees C,
      the intensity of the absorption peak decreased gradually, but a small, broad peak
      remains even at the temperature of 1000 degrees C. For the samples implanted with
      2.8x10(16) Ag ion cm(-2) at the high energy of 3 MeV, one broad absorption peak
      was observed at around 470 nm. As the sample was heated sequentially to high
      temperatures, the peak gradually decreased and almost disappeared at 400 degrees
      C. When the sample was further heated to even higher temperatures, the absorption
      peak at 514 nm reappeared at 1000 degrees C and grew with heating time.

PMID- 10967503
TI  - Electrochemical characterization for ion-implanted materials surfaces.
AB  - Studies on the surface modification of materials by ion implantation have been
      carried out during the past 25 years in RIKEN. In this paper, results of
      electrochemical studies on the ion-implanted materials are described to realize
      the unique substances formed by the ion implantation. The ion implantation is
      used for compositional and structural surface modification of iron and carbon
      substrates. Voltammetric behavior of ion-implanted iron electrodes characterized
      effects of the ion implantation on anodic dissolution and passivation properties
      of the modified surfaces. Typical electrode reaction properties of ion-implanted
      carbon electrodes clearly were related to the effects of structural modification
      of the carbon surfaces.

PMID- 10967504
TI  - The properties of BCN films formed by ion beam assisted deposition.
AB  - A study has been made on the formation and the properties of boron carbonnitride
      (BCN) thin films. The BCN films were produced by ion beam assisted deposition, in
      which boron and carbon were deposited by electron beam heating and nitrogen was
      supplied by ion implantation simultaneously. The mechanical properties of BCN
      films were measured using a ultra micro hardness tester and a friction tester.
      The atomic ratio and the structure of BCN thin films were estimated by means of X
      ray photoelectron spectroscopy, laser Raman spectroscopy and Fourier transform
      infrared spectroscopy. As preliminary results, it was found that the BCN films
      are higher in hardness and lower in friction coefficient than diamond-like carbon
      (DLC) films. The mechanical properties are discussed with the relation of surface
      composition and structure.

PMID- 10967505
TI  - EC-IBD: a European effort in inflammatory bowel disease.

PMID- 10967506
TI  - Changes in the incidence of inflammatory bowel disease: what does it mean?
AB  - A sharp rise in the incidence of inflammatory bowel disease (IBD) has been
      observed in the western world since the early 1950s. The increase in the
      incidence of ulcerative colitis preceded the increase in the incidence of Crohn's
      disease by about 10-15 years. In high-incidence areas, a female preponderance at
      a young age (20-40 years) is observed in Crohn's disease, whereas in ulcerative
      colitis male incidence is still high at older ages. IBD is more common in the
      developed world than in the developing world and, in both the United States and
      Europe, a north-south incidence gradient has been reported, with IBD more common
      in the north than in the south. There are also indications that, in typically low
      incidence areas, more cases are being seen lately. At present, IBD is rather
      common in western Europe, affecting 0.5-1.0% of the population during their
      lifetime. It will be interesting to follow these temporal trends in the coming
      years, as they may teach us more about the role of environmental factors in the
      pathogenesis of IBD.

PMID- 10967507
TI  - Medical treatment: does it influence the natural course of inflammatory bowel
      disease?
AB  - It is difficult to predict the clinical course of inflammatory bowel disease
      (IBD). Moderately sick Crohn's disease (CD) patients and patients with distal
      ulcerative colitis (UC) may get better even without medical or surgical
      treatment. Once better, they may continue in remission even without treatment. If
      they are not treated, there are several factors that predict whether they will
      maintain remission. Most patients will probably alternate between remission and
      relapse, with 10% having a relapse-free course after 10 years, and only 1% having
      a continuously active course. Frequent relapses initially are associated with
      active disease later on, but the disease activity course is independent of the
      response to the initial medical treatment. There is a cumulative frequency of
      operation of 50-80% and of reoperation of 33% in CD, which suggests that CD has a
      more serious course than UC. In UC, the overall probability of surgery is 33% for
      pancolitis and 10% for proctitis within 5 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 UC has reduced relapse
      rates to about half over a 1-year follow-up period. The use of 5-ASA for
      maintenance of CD has been shown to result in only a modest therapeutic gain,
      while azathioprine and 6-mercaptopurine (6-MP) improve the relapse frequency for
      at least 3 years whilst on treatment. Changes in disease distribution in UC are
      part of the natural course of the disease, which should have implications for
      medical treatment strategies, and affects the risk of colectomy and colonic
      cancer. Certain enviromental factors are thought to determine disease activity
      and disease outcome in UC and CD. Patient compliance with prescribed medication
      and clinical check-ups must be considered another non-specific variable affecting
      the clinical outcome. IBD frequently requires potent medication with side effects
      that limit patients' acceptance. Such patients often resort to medicinal herbs,
      acupuncture, and homeopathy, which may alter the expected course.

PMID- 10967508
TI  - Genotype-phenotype relationship in inflammatory bowel disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases of unknown
      etiology. Much effort has been made in the last years to clarify the pathogenesis
      of inflammatory bowel disease (IBD). Data are not conclusive at the moment, but
      the most important known risk factor for developing IBD is a positive familial
      history. Genetic analyses have shown a linkage between loci on several
      chromosomes and IBD (IBD1 gene on chromosome 16 for CD and on chromosome 12 for
      UC). The association of genotype to specific phenotypes of disease could be
      hypothesized by the concordance of clinical characteristics in familial IBD, by
      the association of specific HLA haplotypes to clinically different groups of
      patients, and by different responses to treatment related to different
      polymorphisms of other chromosome 6 genes. The clinical heterogeneity of IBD has
      led to classifications of patients with Crohn's disease based upon clinical
      features (e.g. Rome and Vienna classifications) that allow the identification of
      subgroups of patients with similar clinical behavior. The possible drawbacks of
      these classifications are the lack of validation of intra-interobserver
      concordance, the absence of prospective evaluations, and stratification into too
      many subgroups. Furthermore, in our experience, clinical presentation (surgical
      or medical) seems to have a good correlation with prognosis, is easy
      identifiable, and can be applied at the time of diagnosis. In UC, extension of
      disease and clinical behavior correlate with prognosis. For these reasons,
      studies correlating genotype to phenotype should be performed to improve our
      knowledge of the diseases and possibly to stratify patients into different
      subgroups for more personalized treatments, in clinical trials and for research
      purposes.

PMID- 10967509
TI  - Musculoskeletal manifestations in inflammatory bowel disease.
AB  - Musculoskeletal manifestations are the most common extra-intestinal complication
      of inflammatory bowel disease (IBD). They are part of the clinical spectrum of
      spondylarthropathies and include different articular manifestations. In addition
      to axial symptoms, peripheral findings such as seronegative oligoarthritis,
      dactylitis, and enthesopathy commonly occur, sometimes representing the only
      manifestation. Wide ranges of prevalence have been reported, depending on the
      criteria used to define spondyloarthropathy and on the selection of patients. In
      an inceptional cohort of newly diagnosed IBD patients, we observed
      musculoskeletal manifestations in 30.7% of the patients. The clinician should,
      therefore, carefully evaluate any rheumatological findings in order to provide an
      accurate and early diagnosis, and to establish an adequate therapy. In this
      article, epidemiological, clinical, and diagnostic aspects are discussed.
      Furthermore, the contribution of intestinal bacteria and immunogenetic factors to
      the pathogenesis of arthritis is briefly reviewed. Finally, we summarize the
      available therapeutic options.

PMID- 10967510
TI  - Pregnancy, fertility, and disease course in patients with Crohn's disease and
      ulcerative colitis.
AB  - Pattern recognition of the long-term disease course before, during, and after
      pregnancy can provide us with data about the influence of pregnancy on IBD, and
      vice versa. Determinants that predict an indolent versus an aggressive disease
      course are currently being sought. Our intention is to analyze the disease course
      during pregnancy in an EU-IBD inception cohort of 1200 patients diagnosed from
      1991 to 1993 and followed up for 10 years. We also attempt to evaluate such
      factors as smoking and medication and to predict pregnancy course and fertility
      in IBD as well as in a cross-sectional study of members of the patient
      organization EFCCA. One of the questions that arose was: what factor is
      responsible for the observation that pregnancy decreases the incidence of
      relapses and the development of fibrostenotic lesions? Relaxin and the
      glycoprotein YKL-40 are validated in the cohort. The protein relaxin, produced by
      the corpus luteum during pregnancy, increases the laxity of fibrous tissue.
      Collagen fibers are dissolved and disorganized. As maternal rejection of the
      fetus does not occur, a protein from the fetal lymphocytes most likely decreases
      the maternal lymphocyte response. Multiparity may lead to subtle, acquired immune
      deficits. Glycoprotein YKL-40, which causes fibrosis in RA and cirrhosis, is
      speculated to be lower in multiparous women than in nonpregnant women due to the
      fetal lymphocytes that secrete a protein that is a potential immune modulator.
      Knowledge gained from future EC-IBD studies may result in new legislation (e.g.
      regarding adoption) that can benefit IBD patients throughout Europe.

PMID- 10967511
TI  - Anemia in inflammatory bowel disease - the role of recombinant human
      erythropoietin.
AB  - Anemia is a common problem in inflammatory bowel disease (IBD). It is related to
      low Karnofsky scores, loss of weight, impaired physical activity, low tolerance
      to the underlying disease, and a poor growth rate in children. Multiple factors
      can contribute to the anemia in IBD, such as iron, folic acid or B(12)
      deficiency, treatment with immunosuppressive drugs or sulfasalazine, hemolysis,
      and anemia of chronic disease. Anemia of chronic disease is characterized by
      impaired iron utilization, lower erythropoietin (EPO) production than needed, and
      a low response of bone marrow erythroid progenitor cells to EPO. In recent years,
      recombinant human erythropoietin (rhEPO) has been used in combination with iron
      for the correction of refractory anemia in IBD patients (adults or children) with
      good results. There is increasing evidence that rhEPO may correct refractory
      anemia in IBD (both ulcerative colitis (UC) and Crohn's disease (CD)). In
      addition, such therapy may give IBD patients the opportunity to predonate blood
      before surgery and to avoid blood transfusions. One must not forget to exclude or
      correct other causes of anemia in IBD patients before administering rhEPO.
      Furthermore, the enhancement of erythropoiesis by EPO makes it mandatory to
      administer oral or intravenous iron supplementation during therapy to meet the
      increased demand. rhEPO is safe in IBD patients. Further studies with larger
      numbers of patients are needed to optimize the therapy with rhEPO in the
      refractory anemia of IBD.

PMID- 10967513
TI  - Editorial.

PMID- 10967512
TI  - Influence of quality of care on quality of life in inflammatory bowel disease
      (IBD): literature review and studies planned.
AB  - Inflammatory bowel disease (IBD) is a chronic disorder with an early onset in
      life. Therefore, it is reasonable to assume that IBD patients are in considerable
      need of health care. The quality of life of IBD patients is reported to be
      impaired. Whether optimizing the quality of health care for these patients may
      positively influence their quality of life is a question that has been raised
      often during recent years. This review of the literature on health care research
      discusses different concepts regarding the quality of care assessment in chronic
      disease, stresses the need to see things from the patient's perspective, and
      provides recommendations to optimize health care research. The two most important
      conclusions that can be drawn are that: (1) the relationship between quality of
      health care and quality of life in IBD is one that is certainly worth studying;
      and (2) when developing a means to assess patient data on quality of care, it is
      essential to involve patients from the very start.

PMID- 10967514
TI  - The general well-being of recreational drug users: a survey on the WWW.
AB  - American drug policy is predicated upon a dichotomy between legal drugs and
      illegal drugs - good drugs that enhance health and bad drugs which damage health.
      The fact of psychiatric co-morbidity between substance misuse disorders and other
      mental disorders is commonly taken to mean that drug use is damaging to mental
      health. The purpose of this study was to examine the mental well-being of a
      sample of occasional, recreational drug users. DRUGNET was an on-line survey of
      recreational drug use by non-deviant adults via the WWW. Volunteer subjects
      (n=906) completed the survey over the internet between March and September 1997.
      Mental health was assessed utilizing the General Well-being Schedule (GWBS). A
      complete demographic profile of the sample was taken. The GWBS correlated with
      frequency of use, intoxication levels and types of drugs consumed. This study
      demonstrates the existence of healthy, normally functioning adults who
      occasionally use psychoactive drugs.

PMID- 10967515
TI  - The transfer of harm-reduction strategies into prisons: needle exchange
      programmes in two German prisons.
AB  - In Autumn 1995, the Minister of Justice of Lower Saxony (a northern state of
      Germany) gave the green light for the implementation of a 2-year pilot project.
      This project provided for the distribution of sterile injection equipment and
      provision of communicative methods of prevention to drug addicted inmates in a
      women's prison with 170 inmates (Vechta) and a men's prison with 230 inmates
      (Lingen). The decision to go ahead with the project was based on positive
      experiences in Swiss prisons and the supporting recommendations of a panel of
      experts. The pilot project in Vechta started on 15 April 1996, using five
      dispensing machines which allow a needle exchange to guarantee an anonymous
      access. The project in the men's prison started on 15 July 1996. Here the staff
      of the drug counselling service and of the health care unit hand out sterile
      syringes to inmates. The social scientific evaluation was carried out by the Carl
      von Ossietzky University in Oldenburg. The study focused on the aim of the
      project which is to assess the feasibility, usefulness and efficacy of the
      measures undertaken. Of special interest was whether and how changes occured in
      the prison system itself (i.e. acceptance of the measures by staff, medical
      service and management), and in the drug user's behaviour and knowledge (i.e.
      development of needle sharing, change in drug use patterns). The study used a
      multi-methodological approach: documentation of the project practice, half
      standardized, longitudinal examination of inmates (n=224) and staff (n=153),
      qualitative examination of management, selected groups of prisoners, staff and
      external organisations (AIDS-Help-Groups; n=75) for at least two times. The
      evaluation intended to be dynamic, process accompanying, in order to communicate
      the empirical data and developments with the practice already during the pilot
      phase. Results of the final report of the study are presented here. Finally this
      paper discusses shortly what is known so far about the impact of needle exchange
      programmes in prisons in Germany and Switzerland.

PMID- 10967516
TI  - The limits of therapeutic models of substance misuse for policy and practice. A
      qualitative study of two agencies.
AB  - This paper presents the analysis from a qualitative study of two substance misuse
      treatment agencies, one based on the Twelve Step AA model and one on a Cognitive
      Behavioural approach. Analysis of ethnographic data and 38 semi-structured
      interviews with staff indicated that the agencies were in practice using very
      similar methods. However, the use of particular therapist models gave rise to
      different definitions of problems, assessment and notions of success. The paper
      considers the implications of these findings for policy and practice. It
      distinguishes between the therapeutic usefulness of theory and its role in
      focusing assessment procedures, limiting interventions, defining success and
      determining the timing of treatment termination. It considers how far models
      might influence purchasing and service development through research and
      evaluation.

PMID- 10967517
TI  - Black powder drugs: an innovative response to drug control policy.
AB  - As the intensity of the War on Drugs escalates, the social control of drug
      interdiction crosses international borders and employs more technologically
      advanced detection and apprehension tactics. In response to this intensification,
      drug traders develop advanced counter-surveillance strategies that diminish their
      chances of being detected and apprehended. This results in an interesting
      relationship between those who choose to indulge in drug-related behavior and
      agents who actively try to detect, identify, and apprehend drug traders. Drug
      traders appear to have recently gained the upper hand with the production of
      "Black Powder," which represents the most innovative and effective anti
      surveillance technique to date. Black powder is a simple industrial cloaking
      method that renders many surveillance strategies and chemical tests futile. Black
      powder is but one evolution in this exchange driven by tangible rewards, which
      results in intensified anti-drug strategies and an escalation of social control.

PMID- 10967518
TI  - Consideration of a North American heroin-assisted clinical trial for the
      treatment of opiate-dependent individuals.
AB  - Untreated opiate addiction remains a major public health problem in North America
      (US and Canada). Increased morbidity and mortality as well as criminal behavior
      related to untreated opiate dependence constitute significant social and economic
      burdens. While the principal treatment modality to opiate addiction in North
      America has been methadone treatment since the 1960s, its reach and effectiveness
      has been limited; at any given time, only about 25% (US) and 15-20% (Canada) of
      all opiate addicts are in methadone treatment. Reasons for low levels of
      treatment participation among this subset of users include perceptions among
      users that treatment programs are punitive and that the medication is fraught
      with side effects. In the meantime, alternatives to methadone have been recently
      approved or are in development, including levo-alpha acetylmethadol and
      buprenorphine. However, the extent to which they will solve the current problem
      is still unknown, and therefore development of additional treatment strategies
      needs to continue. Recent studies of heroin-assisted treatment in Europe
      (Switzerland, the Netherlands and Great Britain) produced preliminary yet
      encouraging results in attracting and retaining long-term, treatment-resistant
      addicts in treatment, as well as improving treatment outcomes. However
      encouraging, the North American context differs from Europe. A study performed in
      North America would provide critical information on whether utilizing injectable
      opiates enhances the overall therapeutic attractiveness and effectiveness of
      substance abuse treatment to a subset of recalcitrant users. Implications of
      positive results would expand the continuum of effective interventions in the US
      and Canada, and increase the number of long-term, treatment-resistant opiate
      addicts in treatment.

PMID- 10967519
TI  - Dynamics of molecules in crystals from multi-temperature anisotropic displacement
      parameters. I. theory
AB  - A new model for analysing the temperature evolution of anisotropic displacement
      parameters (ADP's) is presented. It allows for a separation of temperature
      dependent from temperature-independent contributions to ADP's and provides a
      fairly detailed description of the temperature-dependent large-amplitude
      molecular motions in crystals in terms of correlated atomic displacements and
      associated effective vibrational frequencies. It can detect disorder in the
      crystal structure, systematic error in the diffraction data and the effects of
      non-spherical electron-density distributions on ADP's in X-ray data. The analysis
      requires diffraction data measured at multiple temperatures.

PMID- 10967520
TI  - Dynamics of molecules in crystals from multi-temperature anisotropic displacement
      parameters. II. Application To benzene (C6D6) and urea
AB  - The temperature evolution of atomic anisotropic displacement parameters (ADP's)
      of perdeuterobenzene and of urea in the temperature range between 12 and 123 K is
      investigated in terms of the model presented in paper I. For the benzene
      molecule, the temperature-dependent contributions to the ADP's are well described
      by three molecular librations and three molecular translations. For the urea
      molecule, the analysis revealed a low-frequency high-amplitude normal mode (
      approximately 64 cm(-1)), which combines out-of-plane deformations of the NH(2)
      groups with molecular libration. The pyramidalization motion allows the hydrogen
      bonding pattern to be retained quite well, whereas this pattern is heavily
      distorted in the higher-frequency molecular librations. The results presented for
      urea go a step beyond those obtainable in a conventional rigid-body or segmented
      rigid-body analysis because they show how correlations of atomic displacements in
      molecular crystals can be determined from the temperature evolution of ADP's. For
      both molecules, the analysis reveals temperature-independent contributions to the
      ADP's accounting for the high-frequency internal vibrations. It is the first time
      that such contributions have been extracted directly from single-crystal
      diffraction data for light atoms like hydrogen and deuterium as well as for
      heavier atoms like carbon, nitrogen and oxygen. These contributions agree well
      with those calculated from independent spectroscopic information.

PMID- 10967521
TI  - Anharmonicity in anisotropic displacement parameters
AB  - A quasi-harmonic molecular-mean-field model for analyzing anharmonic temperature
      evolution of anisotropic displacement parameters is described. Anharmonic effects
      are taken into account through a Gruneisen-type temperature dependence of
      effective vibrational frequencies. The method is applied to neutron and X-ray
      diffraction data of hexamethylenetetramine measured between 15 and 298 K. The
      resulting Gruneisen parameters and other characteristics of molecular motion in
      the solid state agree well with those obtained from independent vibrational data.
      The analysis also suggests errors in the ADP's due to insufficient extinction
      corrections in the diffraction data.

PMID- 10967522
TI  - Strategies for structure solution and refinement of small organic molecules from
      electron diffraction data and limitations of the simulation approach
AB  - In recent years, a series of non-linear optically active bis(benzylidene) ketones
      have been synthesized and investigated by electron crystallography. In most
      cases, structure refinement was possible by combining electron diffraction
      analysis and quantum-mechanical calculations with maximum-entropy methods.
      However, when the torsional angles between the phenyl rings and the C=C double
      bonds are strongly affected by the crystal field, this method fails because
      packing-energy calculations are not sufficiently sensitive. This problem can be
      solved by refining the approximate model with SHELXL, if the data set is
      sufficiently accurate and the model close to the correct structure. Here it is
      shown that a considerably superior data set can be obtained at 300 kV with on
      line data acquisition.

PMID- 10967524
TI  - Statistical dynamical direct methods. I. The effective kinematical approximation
AB  - While it is known that the kinematical approximation works poorly if at all for
      transmission electron diffraction, substantial success has been achieved over the
      last few years in applying it via direct methods to determine atomic structures.
      This raises an interesting quandary; is the established theory of electron
      diffraction wrong, or are the apparent successes mirages? The intention of this
      note is to look more deeply into this question and it is found that the correct
      answer is neither of the above. Beyond vanishingly thin samples when the
      kinematical approximation holds rigorously, the distribution of phases can remain
      effectively kinematical; the summation operator(0) distribution given by the sum
      of the phase of +g and -g reflections remains peaked, albeit not at zero phase,
      and has a relatively narrow distribution. This fact is shown via both exploiting
      prior works on including anomalous-scattering effects into direct methods, and
      numerical calculations. Provided that the summation operator(0) distribution
      remains narrow, direct methods and indeed structural refinements have some
      validity. Even larger unit-cell structures with close to statistically random
      atomic positions do not approach a kinematical limit but instead an effective
      statistical kinematical approximation. While there are similarities to what there
      is in conventional (kinematical) direct methods, there remain major differences;
      for instance, positivity is no longer a valid constraint and the scattering need
      not be dominated by heavy atoms.

PMID- 10967523
TI  - SIR2000, a program for the automatic ab initio crystal structure solution of
      proteins.
AB  - A new phasing procedure is described working both in direct and in reciprocal
      space. The procedure has been implemented into the program SIR2000, the heir to
      SIR99, and it is able routinely to solve ab initio crystal structures of proteins
      without any use of prior information and any user intervention. The moduli and
      the flow diagram of SIR2000 are also described and its efficiency tested on
      several protein diffraction data sets. Success has been attained for crystal
      structures with up to almost 2000 non-hydrogen atoms in the asymmetric unit and
      resolution higher than 1.2 A. The phasing process is analysed to provide a better
      insight into the role of the various steps of the procedure.

PMID- 10967525
TI  - Atomic scattering factors for K-shell and L-shell ionization by fast electrons
AB  - Atomic scattering factors have been calculated for K-shell ionization for
      elements in the range Z = 6 (carbon) to Z = 50 (tin) and for L-shell ionization
      in the range Z = 20 (calcium) to Z = 60 (neodymium). The calculations are based
      on relativistic Hartree-Fock wave functions for the atomic bound states and
      Hartree-Slater wave functions for the continuum wave functions. The results are
      presented in tabular form such that accurate values of the scattering factors can
      be obtained by cubic spline interpolation for incident electron energies between
      50 and 400 keV and for scattering vectors with magnitude s = sin straight theta /
      lambda up to 2.5 A(-1) (2straight theta is the scattering angle and lambda the
      wavelength of the incident electrons). A separate parameterization of the form
      factors is given for 2.5 </= s </= 20 A(-1), where they are small. In addition, a
      simpler but less accurate parameterization of the atomic scattering factors in an
      exponential form has been obtained by fitting the calculated form factors in the
      region s </= 2.5 A(-1). The scattering factors are suitable for the calculation
      of ionization cross sections for use in atom location by channelling-enhanced
      microanalysis (ALCHEMI).

PMID- 10967526
TI  - The contraction types of parallelohedra in E5
AB  - Using the process of zone contraction and its inverse, zone extension, the 179372
      contraction types of parallelohedra in E(5) were derived from the 84
      combinatorial types of relatively or totally zone-contracted parallelohedra.

PMID- 10967527
TI  - Diffraction by one-dimensional paracrystals and perturbed lattices
AB  - A detailed comparison of the one-dimensional paracrystalline and perturbed
      lattice models of disordered crystals, and their diffraction, is made. If
      noncumulative (thermal) disorder is added to the paracrystalline model, then the
      two models and their diffraction patterns are similar but not identical because
      of their different intersite statistics. However, they are identical in the
      limiting cases of either strong or weak correlations. Calculation of diffraction
      patterns shows that, with an appropriate choice of parameters, the two models
      give essentially identical diffraction for small crystallites and very similar
      diffraction for larger crystallites. An empirical relationship is derived between
      parameters of the two models such that they give similar diffraction patterns.

PMID- 10967528
TI  - Bragg-surface dynamical diffraction
AB  - In this work, the dispersion surface of Bragg-surface diffraction (BSD) is
      presented. A symmetric Bragg reflection plus a secondary diffracted wave nearly
      parallel to in-plane directions distinguish the BSD from an ordinary three-beam
      diffraction. The solutions of the fundamental equations of the dynamical theory
      of X-ray diffraction for the BSD demonstrate that measurable specular-reflected
      secondary waves are simultaneously excited with the diffracted waves.

PMID- 10967531
TI  - Histochemical and ultrastructural characteristics of leg muscle fibres in
      patients with repairative abdominal aortic aneurysm (AAA).
AB  - Tibialis anterior (ta) muscle biopsies before and after elective abdominal aortic
      aneurysm (AAA) repair operation were obtained, in order to observe possible
      changes after the aortic declamping reperfusion. Open muscle biopsies were taken
      from each of eight patients (60-75 years old) which were processed for enzyme
      histochemistry, and for transmission electron microscopy (EM). Morphometric
      analysis was applied to estimate the number and the area of muscle fibres of each
      fibre type. Rectus abdominis muscle biopsies were served as controls. Before the
      operation the predominant elements found were the presence of atrophic muscle
      fibres, fibre size diversity, localised cellular reactions, increased extent of
      connective tissue, disappearance, in many cases, of the mosaic pattern,
      predominance of type I and oxidative fibres, and existence of fibres with core
      like structures in the sarcoplasm. Type I fibres consisted of 66.95 +/- 9% of all
      muscle fibres, the mean cross sectional area of which was 3,372.8 +/- 1,016
      microm(2) and of type II fibres was 3,786.5 +/- 6,046 microm(2). After the aortic
      clamping was performed mitochondrial swelling was found, as well as
      disorganisation of sarcomeres. After declamping of the aorta, there were also
      severe edema, local fibre necrosis, and adhesion of leucocytes, whereas muscle
      fibre areas became 3,935.18 micro 531 microm(2) for type I and 5,804 +/- 1,075
      microm(2) for type II. The short ischemic period during aortic clamping and the
      subsequent reperfusion resulted mainly in ultrastructural changes.

PMID- 10967532
TI  - Decreased constitutive nitric oxide synthase, but increased inducible nitric
      oxide synthase and endothelin-1 immunoreactivity in aortic endothelial cells of
      donryu rats on a cholesterol-enriched diet.
AB  - The Donryu rat is resistant to a high cholesterol diet in that typical
      atheromatous lesions do not develop. Using electron microscopic
      immunocytochemical techniques, the effects of a CCT diet (4% cholesterol with 1%
      cholic acid and 0.5% thiouracil) on the distributions of neuronal, macrophage,
      and endothelial specific nitric oxide synthase (NOS I, NOS II, and NOS III) and
      endothelin-1 (ET-1) immunoreactivity were examined in the thoracic aortic intima.
      Atheromatous lesions were absent, but immunocytochemistry showed 1. 4+/-0.52% and
      4.0+/-0.9% endothelial cells (EC) with positive staining for NOS I and NOS III,
      respectively, compared with 16.3+/-2. 5% and 88.6+/-2.48% in control Donryu rats.
      The CCT-supplemented diet induced expression of NOS II immunoreactivity in
      thoracic aortic intimal cells. EC, subendothelial macrophages, and smooth muscle
      cells (SMC) also showed high NOS II-positive staining. The percentage of NOS II
      immunoreactive EC was 43+/-1.8%. In control groups, no NOS II immunoreactive
      cells were observed. The percentage of ET-1 immunopositive cells was also
      significantly increased by 9. 2+/-0.66% and 64.2+/-1.4% in control and CCT-fed
      groups, respectively. It is concluded that the administration of a high
      cholesterol diet in Donryu rats produces endothelial dysfunction associated with
      changes in the balance of the different isoforms of NOS and ET-1. Therefore, the
      increase in inducible NOS and ET-1 immunoreactivity seen during the cholesterol
      enriched diet appears to be a compensatory reaction of aortic wall cells to the
      high cholesterol supplementation.

PMID- 10967533
TI  - Pads and flexion creases on the plantar surface of hammertoe mutant mouse (Hm).
AB  - The purpose of the present work was to determine the effects of the hereditary
      malformation of Hammertoe mutant mice (gene symbol Hm) on the surrounding
      morphological structures and, specifically, on the volar pads, i.e., the sites of
      the epidermal ridge patterns (dermatoglyphics). The hindlimbs of the wild-type
      (+/+) Hammertoe mice show no anomalies and their major pad and flexion crease
      configurations correspond to those of normal mice. The heterozygous (Hm/+) and
      homozygous (Hm/Hm) mice display a fusion of the interdigital tissues involving
      all digits with the exception of digit I. In Hm/Hm mice, this webbing extends to
      the distal phalanx and the markedly flexed digits form a shape resembling a
      hammer. In Hm/+ mice, the interdigital webbing does not extend as far and the
      digits show moderate flexion compared to those of Hm/Hm mice. Both Hm/Hm and Hm/+
      have a rudimentary extra digit in the postaxial area of the hindlimbs. The
      ventral volar skin of the flexed digits is incompletely developed. The more
      posterior digits show the more severe camptodactyly. These aberrant
      configurations are related to the abnormal occurrence of the programmed cell
      death (PCD) in the interdigital zones II-IV and the proximal part of the
      postaxial margin during hindlimb development. They are limited to the pads on the
      plantar surface of the postaxial area; the preaxial area is not affected. As a
      result of a severe camptodactyly of digit V, its volar skin is shifted into the
      distal portion of the hypothenar area. This shifting affects the number, size,
      and location of the pads, especially of the hypothenar pad, resulting in varying
      pad configurations, such as a displacement of the distal and proximal components
      of the hypothenar pad, or a fusion of the two components of the hypothenar pad,
      leading to a reduced final pad number. These pad modifications are induced by the
      postaxial plantar surface shifting proximally and are not affected by the
      presence of an extra rudimentary digit. The pad modifications in Hammertoe mice
      with webbed digits and postaxial polydactyly resemble closely those of the
      previously studied mice with genetic preaxial polydactyly.

PMID- 10967534
TI  - Intercalated clear cells or pale cells in the sinus node of canine hearts? An
      ultrastructural study.
AB  - Two types of sinus nodal cells were responsible for the main differences in the
      literature concerning the ultrastructure of the sinuatrial node: the intercalated
      clear cells and pale cells. Canine hearts were arrested by (1) aortic cross
      clamping, (2) coronary perfusion with the cardioplegic solution St. Thomas, and
      (3) coronary perfusion with the cardioplegic solution HTK (Custodiol(R)). After
      fixation by immersion or perfusion the sinus node tissue was prepared for
      electron microscopy. Following cardioplegic arrest and perfusion fixation, three
      nodal cell types in the non-ischemic sinuatrial node were observed: typical nodal
      cells, transitional cells, and intercalated clear cells. Less than 1% of the non
      ischemic sinuatrial cells were intercalated clear cells, surrounded by typical
      nodal cells or transitional cells. The contractile apparatus of the intercalated
      clear cells was extremely poorly developed. Great structural variations in the
      mitochondria were observed in intercalated clear cells, variations that would not
      appear under conditions of ischemia. In contrast, after 15-25 min of ischemia at
      25 degrees C the appearance of the sinus nodal cells was strikingly different
      from that of the non-ischemic sinuatrial cells. More than 10% of the nodal cells
      showed typical ischemic alterations, e.g., mitochondrial swelling, clumping of
      nuclear chromatin, loss of glycogen particles, and cell swelling in varying
      degrees. Because they look very pale, these nodal cells have been described as
      pale cells in the literature. Intercalated clear cells appear mainly in non
      ischemic nodal tissue. Pale cells are ischemically damaged sinus nodal cells.

PMID- 10967535
TI  - Immunohistochemical detection of the estrogen receptor-alpha and progesterone
      receptor in the canine pregnant uterus and placental labyrinth.
AB  - The presence of hormone receptors is as important as the amount of hormone to
      predict hormone action. Therefore, the presence of estrogen receptors of the
      alpha subtype (ER-alpha) and progesterone receptors (PR) was evaluated in six
      pregnant uteri including the placenta and in three postpartum uteri of dogs. This
      preliminary study is part of our immunohistochemical research project on steroid
      hormone receptor distribution in the canine female genital tract. Specific
      staining for ER-alpha or PR was found only in cell nuclei. Staining for ER-alpha
      was rare in the various cell types of pregnant and postpartum uteri. Staining for
      PR was absent or weak in epithelial cells. Moderate staining for PR was observed
      in endometrial stromal cells and myometrial smooth muscle cells, two cell types
      playing an important role in the maintenance of pregnancy. Stromal cells stained
      more frequently positive for ER-alpha and PR than epithelial cells, indicating
      that both hormones may act on epithelial cells indirectly via stromal cells. In
      the placental labyrinth, fetal cells showed no evidence of ER-alpha or PR. In
      contrast, both receptors were present in maternal mesenchymal cells that were
      located around the basement membrane of the maternal blood vessels. These cells
      showed signs of decidualization. No difference in PR distribution was seen
      between pregnant and postpartum uterine tissue, suggesting that during
      parturition the decrease in serum progesterone levels and the concomitant
      increase in the estrogen/progesterone ratio are probably more important than the
      decline in receptor availability.

PMID- 10967536
TI  - Neurovascular plasticity in the knee joint of an arthritic mouse model.
AB  - Lower numbers of neuropeptide-containing fibers in arthritic joints have been
      found as compared to control joints. This may be the result of fiber depletion,
      necrosis of fibers, or proliferation of soft tissues without neural sprouting. To
      discriminate between these possibilities, we studied the relationships between
      soft tissue proliferation, changes in vascularity of synovial tissues, and
      changes in joint innervation during arthritis. Arthritis was induced in the knee
      joint of mice by a single subpatellar injection of methylated bovine serum
      albumin after previous immunization. Antibodies to protein gene product 9.5, S
      100, and growth-associated protein-43 (GAP-43) were used to study the general
      innervation pattern. Antibodies to calcitonin gene-related peptide (CGRP),
      vasointestinal polypeptide (VIP), substance P (SP), and tyrosine hydroxylase (TH)
      were used to localize sensory (SP, CGRP, VIP) and sympathetic (TH) fibers. Blood
      vessels of the joint were studied with ink perfusion, GAP-43, and a vascular
      marker (LF1). Directly after the induction of arthritis, the synovial cavity was
      enlarged and filled with leukocytes. From day 4 onward, small sprouting blood
      vessels penetrated the avascular mass of cells in the joint cavity. After 1 week,
      the vascular sprouting activity and GAP-43 immunoreactivity were maximal, and
      after 2 weeks, vascular sprouting activity diminished. In the subsequent period,
      the synovia slowly regained their prearthritic appearance and thickness. The most
      pronounced changes in the general staining pattern of CGRP, SP, VIP, and TH were
      found in the periosteum. From 2 days to 4 weeks after the induction of arthritis,
      the layer of SP, CGRP, and VIP fibers in the femoral periosteum was thicker and
      more irregular. GAP-43 staining showed many terminal varicosities, which
      suggested sprouting of nerve fibers. From 2 days to 2 weeks after the induction
      of arthritis, the SP and CGRP fibers in the periosteum showed gradual depletion.
      In the thickened subsynovial tissues that were revascularized, no ingrowth of
      neural elements was found. As the total number of nerve fibers in the synovial
      tissue did not change, large parts of the synovia directly facing the joint
      cavity were not innervated at 1 week after the induction of arthritis. These
      results strongly suggest that periosteal SP and CGRP fibers were depleted during
      arthritis. Synovial proliferation without concomitant fiber growth is the main
      cause of the reduced number of immunocytochemically detectable fibers in the
      mouse arthritic knee joint.

PMID- 10967537
TI  - Histological studies of pedicle skin formation and its transformation to antler
      velvet in red deer (Cervus elaphus).
AB  - Deer antlers and their antecedent pedicles are made up of two components,
      interior osseocartilage and exterior integument. In a previous study, we
      described that histogenesis of the interior osseocartilage proceeds through four
      ossification stages. These are intramembranous (IMO), transition (OPC), pedicle
      endochondral (pECO), and antler endochondral (aECO). In the present study, we
      used histological techniques to examine pedicle skin formation and its
      transformation to antler velvet. The results showed that pedicle skin initiated
      from the apex of a frontal lateral crest and was formed through three distinctive
      stages. These stages are 1) compression of the subcutaneous loose connective
      tissue at the OPC stage, 2) stretching of the undulated epidermis at the early
      pECO stage, and 3) neogenesis of the skin and its associated appendages at the
      mid pECO stage. Transformation into antler velvet, which occurs at the late pECO
      stage, is mainly associated with alteration in the skin appendages. This
      alteration includes the loss of arrector pili muscle and sweat glands, and the
      gain of the large bi- or multi-lobed sebaceous glands. These results suggest that
      pedicle skin expansion occurs to release the mechanical tension created by
      underlying forming antlerogenic tissue, initially in response to it by mechanical
      stretch, and then by neogenesis of skin. In turn, the stretched pedicle skin may
      exert mechanical pressure on the underlying antlerogenic tissue causing it to
      change in ossification type. Antler velvet generation may be accomplished by both
      mechanical stimulation and chemical induction from the underlying pECO stage
      antlerogenic tissue. If this hypothesis is correct it is likely that mechanical
      stimulation would drive skin formation and chemical induction then determine skin
      type. Furthermore, asynchronous transformation of the interior and exterior
      components during pedicle formation and antler generation may result from the
      delayed chemical induction and the way antler velvet initially generates. The
      results from both mitotic cell labelling of the basal layer and ultrastructure of
      the basement membrane of the apical skin in the study support these hypotheses.

PMID- 10967538
TI  - Bisphosphonate administration alters subcellular localization of vacuolar-type
      H(+)-ATPase and cathepsin K in osteoclasts during experimental movement of rat
      molars.
AB  - This study was designed to clarify the effects of bisphosphonate (BP)
      administration on structure and functions of osteoclasts in alveolar bone
      resorption during experimental movement of rat molars. To produce orthodontic
      force, elastic band was inserted between the upper first and second molars for 4
      days, and dissected maxillae were then examined by means of light and electron
      microscopic immunocytochemistry for vacuolar-type H(+)-ATPase and lysosomal
      cystein proteinase, cathepsin K in osteoclasts. Vacuolar-type H(+)-ATPase and
      cathepsin K in osteoclasts are the most important enzymes for demineralization of
      apatite crystals and degradation of bone type-I collagen, respectively. At 1 day
      before elastic band insertion, BP was administered intraperitoneally. Control
      rats received the same volume of physiologic saline. In BP-administered rats,
      most osteoclasts exhibited either irregularly-formed ruffled borders and clear
      zones or only clear zones of various degrees of extension. Subcellular
      localization and expression of both vacuolar-type H(+)-ATPase and cathepsin K was
      significantly decreased in such osteoclasts with impaired ruffled borders and/or
      only clear zones by BP administration. In particular, cathepsin K secretion by
      osteoclasts towards resorption lacunae was markedly inhibited by BP
      administration. Our results indicate for the first time that BP administration
      significantly impair the osteoclast structure and reduces expression of both
      vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during tooth movement.

PMID- 10967539
TI  - Anatomy of the human atrioventricular junctions revisited.
AB  - There have been suggestions made recently that our understanding of the
      atrioventricular junctions of the heart is less than adequate, with claims for
      several new findings concerning the arrangement of the ordinary working
      myocardium and the specialised pathways for atrioventricular conduction. In
      reality, these claims are grossly exaggerated. The structure and architecture of
      the pathways for conduction between the atrial and ventricular myocardium are
      exactly as described by Tawara nearly 100 years ago. The recent claims stem from
      a failure to assess histological findings in the light of criterions established
      by Monckeberg and Aschoff following a similar controversy in 1910. The
      atrioventricular junctions are the areas where the atrial myocardium inserts
      into, and is separated from, the base of the ventricular mass, apart from at the
      site of penetration of the specialised axis for atrioventricular conduction.
      There are two such junctions in the normal heart, surrounding the orifices of the
      mitral and tricuspid valves. The true septal area between the junctions is of
      very limited extent, being formed by the membranous septum. Posterior and
      inferior to this septal area, the atrial myocardium overlies the crest of the
      ventricular septum, with the atrial component being demarcated by the landmarks
      of the triangle of Koch. The adjacent structures, and in particular the so-called
      inferior pyramidal space, were accurately described by McAlpine (Heart and
      Coronary Arteries, 1975). Thus, again there is no need for revision of our
      understanding. The key to unravelling much of the alleged controversy is the
      recognition that, as indicated by Tawara, the atrioventricular node becomes the
      atrioventricular bundle at the point where the overall axis for conduction
      penetrates into the central fibrous body. There are also marked differences in
      arrangement, also described by Tawara, between the disposition of the conduction
      axis in man as compared to the dog.

PMID- 10967540
TI  - Comparative morphology and histochemistry of glands associated with the
      vomeronasal organ in humans, mouse lemurs, and voles.
AB  - The vomeronasal organ (VNO) is a chemosensory structure of the vertebrate nasal
      septum that has been recently shown to exist in nearly all adult humans. Although
      its link to reproductive behaviors has been shown in some primates, its
      functionality in humans is still debated. Some authors have suggested that the
      human VNO has the capacity to detect pheromones, while others described it as
      little more than a glandular pit. However, no studies have utilized histochemical
      techniques that would reveal whether the human VNO functions as a generalized
      gland duct or a specialized chemosensory organ. Nasal septal tissue from 13
      humans (2-86 years old) were compared to that of two adult lemurs (Microcebus
      murinus) and eight adult voles (four Microtus pennsylvanicus and four Microtus
      ochrogaster). Sections at selected intervals of the VNO were stained with
      periodic acid-Schiff (PAS), alcian blue (AB), AB-PAS, and PAS-hematoxylin
      procedures. Results revealed typical well-developed VNOs with tubuloacinar glands
      in Microtus and Microcebus. VNO glands were AB-negative and PAS-positive in voles
      and mouse lemurs. Homo differed from Microtus and Microcebus in having more
      branched, AB and PAS-positive glands that emptied into the VNO lumen.
      Furthermore, the human VNO epithelium had unicellular mucous glands (AB and PAS
      positive) and cilia, similar to respiratory epithelia. These results demonstrate
      unique characteristics of the human VNO which at once differs from glandular
      ducts (e.g., cilia) and also from the VNOs of mammals possessing demonstrably
      functional VNO.

PMID- 10967541
TI  - Differential expression of cSmad1 and cSmad5 in the primitive streak during chick
      embryo gastrulation.
AB  - Whole mount in situ hybridization was performed to determine the expression
      patterns of cSmad1 and cSmad5 during gastrulation stages (Hamburger-Hamilton 2-6)
      of chicken embryogenesis. It was revealed that cSmads 1 and 5 mRNAs are
      prominently expressed in the developing primitive streak. As determined from
      cross-sectional analysis of stage 4 embryos, most transcripts were associated
      with the ingressing mesoderm. However, whereas cSmad5 was expressed throughout
      the streak at all stages examined, the strongest expression of cSmad1 was
      confined to the posterior half of the streak.

PMID- 10967543
TI  - Editorial.

PMID- 10967544
TI  - Announcing EarlyView((R))-Another enhancement to Wiley InterScience, your gateway
      to Wiley publications online.

PMID- 10967542
TI  - Ectodermal markers delineate the neural fold interface during avian neurulation.
AB  - The formation and morphogenesis of the neural folds are important processes
      underlying neurulation. We showed previously that these processes comprise four
      key events in avian embryos: epithelial ridging, kinking, delamination, and
      apposition. Collectively, these events establish the paired, bilaminar neural
      folds, which fuse in the dorsal midline during late neurulation to close the
      neural groove and to establish the neural tube. Here, we use an antisense
      riboprobe for a new gene called Plato, as well as an antibody for a previously
      cloned transcription factor, AP-2, as markers to identify critical subpopulations
      of ectodermal cells during the formation and morphogenesis of the avian neural
      folds. Plato antisense riboprobe marks the cranial neural ectoderm and
      premigratory cranial neural crest cells, whereas AP-2 antibody marks the
      epidermal ectoderm and the early migratory neural crest. We show that
      subpopulations of ectodermal cells at the forebrain and midbrain levels undergo
      considerable rearrangement within the neural fold transition zone, which
      redistributes incipient neural crest cells from the neural ectodermal side of the
      forming neural fold interface to the epidermal ectodermal side. Additionally, we
      show that Plato and AP-2 provide useful markers for delineating the incipient
      neural fold interface.

PMID- 10967545
TI  - Membrane signaling and progesterone in female and male osteoblasts. II. Direct
      involvement of G alpha q/11 coupled to PLC-beta 1 and PLC-beta 3.
AB  - We have shown that progesterone (10 pM-10 nM) and progesterone covalently bound
      to bovine serum albumin (P-CMO BSA; 100 pM-1 microM) rapidly increased (within 5
      s) the cytosolic free Ca(2+) concentration and inositol 1,4,5 trisphosphate
      (InsP(3)) formation in confluent female and male rat osteoblasts via a pertussis
      toxin-insensitive G-protein. The activation of G-proteins coupled to effectors
      such as phospholipase C (PLC) is an early event in the signal transduction
      pathway leading to InsP(3) formation. We used antibodies against the various PLC
      isoforms to show that only PLC-beta1 and PLC-beta 3 were involved in the Ca(2+)
      mobilization and InsP(3) formation induced by both progestins in female and male
      osteoblasts, whereas PLC-beta 2, PLC-gamma 1, and PLC-gamma 2 were not. We also
      used antibodies against the subunits of heterotrimeric G-proteins to show that
      the activation of PLC-beta 1 and PLC-beta 3 by both progestins involved the G
      alpha q/11 subunit, which was insensitive to pertussis toxin, whereas G alpha i,
      G alpha s, and G beta gamma subunits were not. The membrane effects were
      independent of the concentration of nuclear progesterone receptor, because the
      concentration of nuclear progesterone receptors was lower in male than in female
      osteoblasts. These data suggest that progesterone and P-CMO BSA, which does not
      enter the cell, directly activate G-protein leading to the very rapid formation
      of second messengers without involving the nuclear receptor.

PMID- 10967546
TI  - Regulation of collagenase-3 gene expression in osteoblastic and non-osteoblastic
      cell lines.
AB  - Collagenase-3 expression in osteoblastic (UMR 106-01, ROS 17/2.8) and non
      osteoblastic cell lines (BC1, NIH3T3) was examined. We observed that parathyroid
      hormone (PTH) induces collagenase-3 expression only in UMR cells but not in BC1
      (which express collagenase-3 constitutively) or ROS and NIH3T3 cells. Since we
      know from UMR cells that the AP-1 factors and Cbfa1 are required for collagenase
      3 expression, we analyzed the expression and PTH regulation of these factors by
      gel shift and Northern blot analysis in all cell lines. Gel mobility shift with a
      [(32)P]-labeled collagenase-3 AP-1 site probe indicated the induction of c-Fos in
      osteoblastic cells upon PTH treatment. While c-fos was induced in UMR cells, both
      c-fos and jun B were induced in ROS cells. Since Jun B is inhibitory of Fos and
      Jun in the regulation of the rat collagenase-3 gene in UMR cells, it is likely
      that high levels of Jun B prevent PTH stimulation of collagenase-3 in ROS cells.
      When we carried out gel shift analysis with a [(32)P]-labeled collagenase-3 RD
      (runt domain) site probe and Northern blot analysis with a Cbfa1 specific probe,
      we have observed the presence of Cbfa1 in both osteoblastic and non-osteoblastic
      cell lines, but there was no change in the levels of Cbfa1 RNA or protein in
      these cells under either control conditions or PTH treatment. From our studies
      above, it is evident that the expression of collagenase-3 and its regulation by
      PTH in osteoblastic and non-osteoblastic cells may be influenced by differential
      temporal stimulation of the AP-1 family members, especially c-Fos and Jun B along
      with the potential for posttranslational modification(s) of Cbfa1.

PMID- 10967547
TI  - Differential alteration of catecholamine release during chemical hypoxia is
      correlated with cell toxicity and is blocked by protein kinase C inhibitors in
      PC12 cells.
AB  - Release of neurotransmitters, including dopamine and glutamate, has been
      implicated in hypoxia/ischemia-induced alterations in neuronal function and in
      subsequent tissue damage. Although extensive studies have been done on the
      mechanism underlying the changes in glutamate release, few have examined the
      mechanism that is responsible for the changes in catecholamines. Rat
      pheochromocytoma-12 (PC12) cells synthesize, store, and release catecholamines
      including DA and NE. Therefore, we used HPLC and ED to evaluate extracellular DA
      and NE concentrations in a medium during chemical hypoxia in PC12 cells. Chemical
      hypoxia produced by KCN induced differential release of DA and NE. Under normal
      glucose conditions, KCN induced release of NE, but not DA. Under glucose-free
      conditions, KCN-induced release of DA was elevated transiently, whereas the
      release of NE increased progressively. Under parallel conditions, KCN
      biphasically elevated the level of cytosolic free calcium ([CA(2+)](i)) in
      glucose-free DMEM, peaking at 95 +/- 18 nM at 1,107 +/- 151 s, followed by a new
      plateau level at 249 +/- 24 nM sustained from 4,243 +/- 466 to 5,263 +/- 440 s.
      Cell toxicity, as measured by LDH release, was increased significantly by KCN in
      glucose-free DMEM but was diminished in the presence of glucose, and was
      correlated with DA release by chemical hypoxia. The protein kinase C (PKC)
      inhibitor GO6976 or staurosporine inhibited KCN-induced LDH release as well as
      the release of NE and DA. Taken together, selective activation of DA but not NE
      was correlated with the LDH release by chemical hypoxia, and was diminished with
      GO6976 or staurosporine. These results suggest that selective activation of PKC
      isoforms is involved in the chemical hypoxia-induced DA release, which may lead
      to neuronal cell toxicity.

PMID- 10967548
TI  - Tumor metastasis-associated human MTA1 gene: its deduced protein sequence,
      localization, and association with breast cancer cell proliferation using
      antisense phosphorothioate oligonucleotides.
AB  - Using differential cDNA library screening techniques based on metastatic and
      nonmetastatic rat mammary adenocarcinoma cell lines we previously cloned and
      sequenced the metastasis-associated gene mta1. Using homology to the rat MTA1
      gene we cloned the human MTA1 gene and found it to be overexpressed in a variety
      of human cell lines. We found a close similarity between the human MTA1 and rat
      MTA1 genes, as shown by 88% and 96% identities of the nucleotide and predicted
      amino acid sequences, respectively. Both genes encode novel proteins that contain
      a proline-rich region (SH3 binding motif), a putative zinc finger motif, a
      leucine zipper motif, and five copies of the SPXX motif often found in gene
      regulatory proteins. Using Southern blot analysis, the MTA1 gene was found to be
      highly conserved among all species examined; and using Northern blot analysis,
      MTA1 transcripts were found in virtually all cell lines of human origin that were
      analyzed, including melanoma and breast, cervix and ovarian carcinoma cells and
      normal breast epithelial cells. However, the expression level of the MTA1 gene in
      a normal breast epithelial cell was approximately 50% of that found in rapidly
      growing breast adenocarcinoma cell lines and an atypical mammary cell line.
      Experimental inhibition of MTA1 protein expression using antisense
      phosphorothioate oligonucleotides resulted in growth inhibition of human MDA-MB
      231 breast cancer cells with relatively high expression of the MTA1 gene.
      Furthermore, the MTA1 protein was localized in the nuclei of cells transfected
      using a mammalian expression vector containing the full-length MTA1 gene. The
      results suggest that the MTA1 protein may function in cellular signaling
      processes important in the progression and growth of cancer cells, possibly as a
      nuclear regulatory factor.

PMID- 10967550
TI  - Nuclear import and DNA binding of human papillomavirus type 45 L1 capsid protein.
AB  - During the life cycle of human papillomaviruses (HPVs), the L1 capsid proteins
      seem to enter the nucleus twice: once after the virions infect the cells, and
      later during the productive phase when they assemble the replicated HPV genomic
      DNA into infectious virions. We established for the high-risk HPV45 that when
      digitonin-permeabilized HeLa cells were incubated with L1 homopentameric
      capsomers, the HPV45 L1 protein was imported into the nucleus in a receptor
      mediated manner. In contrast, intact capsids were not able to enter the nucleus.
      Immunoisolation assays showed that HPV45 L1 capsomers interact with cytosolic
      karyopherin alpha 2 beta 1 heterodimers. HPV45 L1 bound strongly to karyopherin
      alpha 2, and weakly to karyopherin beta 1, as did its nuclear localization signal
      (NLS). Nuclear import of HPV45 L1, or of a GST-NLS(HPV45L1) fusion protein was
      efficiently mediated by karyopherin alpha 2 beta 1 heterodimers, and only weakly
      by karyopherin beta 1. Nuclear import required RanGDP, but was independent of GTP
      hydrolysis by Ran. Together, these data suggest that the major nuclear import
      pathway for HPV45 L1 major capsid protein in infected host cells is mediated by
      karyopherin alpha 2 beta 1 heterodimers and that GTP hydrolysis by Ran is not
      required for import. Remarkably, HPV45 L1 capsomers can interact nonspecifically
      with different types of HPV-DNA, and the DNA binding region of HPV45 L1 overlaps
      with its NLS sequence.

PMID- 10967549
TI  - The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane
      spanning proteoglycan NG2.
AB  - A yeast two-hybrid screen was employed to identify ligands for the cytoplasmic
      domain of the NG2 chondroitin sulfate proteoglycan. Two overlapping cDNA clones
      selected in the screen are identical in sequence to a DNA segment coding for the
      most amino-terminal of the 13 PDZ domains found in the multi-PDZ-protein MUPP1.
      Antibodies made against recombinant polypeptides representing these two clones
      (NIP-2 and NIP-7) are reactive with the same 250-kDa molecule recognized by anti
      MUPP1 antibodies, confirming the presence of the NIP-2 and NIP-7 sequences in the
      MUPP1 protein. NIP-2 and NIP-7 GST fusion proteins effectively recognize NG2 in
      pull-down assays, demonstrating the ability of these polypeptide segments to
      interact with the intact proteoglycan. The fusion proteins fail to bind NG2
      missing the C-terminal half of the cytoplasmic domain, emphasizing the role of
      the NG2 C-terminus in the interaction with MUPP1. The existence of an NG2/MUPP1
      interaction in situ is demonstrated by the ability of NG2 antibodies to co
      immunoprecipitate both NG2 and MUPP1 from detergent extracts of cells expressing
      the two molecules. MUPP1 may serve as a multivalent scaffold that provides a
      means of linking NG2 with key structural and/or signaling components in the
      cytoplasm.

PMID- 10967551
TI  - Induction of the urokinase plasminogen activator system by oncostatin M promotes
      endothelial migration.
AB  - Oncostatin M (OSM) is an inflammatory cytokine produced by activated macrophages
      and T-lymphocytes. We have previously demonstrated that OSM-induced endothelial
      cell migration, unlike endothelial cell proliferation and spindle formation, is
      independent of basic fibroblast growth factor expression (Wijelath et al. [1997]
      J. Cell. Sci. 110:871-879). To better understand the mechanism of OSM-induced
      endothelial cell migration, this study examined the potential role of the
      plasminogen activator system in promoting OSM mediated endothelial cell
      migration. OSM stimulated increased mRNA levels of urokinase-plasminogen
      activator (uPA) and urokinase-plasminogen activator receptor (uPAR) in a time and
      dose-dependent manner. Transcriptional run-off and mRNA stability analysis
      demonstrated that the increase in uPA and uPAR mRNA levels was due to both
      increased gene transcription and mRNA stability. The increase in mRNA correlated
      with increased protein levels of both uPA and uPAR. This increase was reflected
      in elevated levels of membrane-bound plasmin activity. OSM-induced endothelial
      cell migration was only partially dependent on plasmin activity since incubating
      endothelial cells without plasminogen or, in the presence of aprotinin, resulted
      in suppression of endothelial cell migration, indicating that OSM promoted
      endothelial cell migration through both a plasmin-dependent and -independent
      mechanism. Our results imply a role for OSM in promoting endothelial cell
      migration via a plasmin-dependent pathway and a uPAR-mediated pathway. Together,
      these and other recent studies support a role for OSM in modulating the different
      phases of angiogenesis.

PMID- 10967552
TI  - Human DNA-demethylating activity: a glycosylase associated with RNA and PCNA.
AB  - We have partially purified and characterized the 5-methylcytosine removing
      activity (5-meC-DNA Glycosylase) from HeLa cells with 700-fold enrichment. This
      activity cleaves DNA specifically at fully methylated CpG sites. The mechanism of
      5-meC removal is base excision from fully methylated CpG loci on DNA, producing
      abasic sites. Hemi-methylated DNA is not a substrate. A prominent 52 KDa protein
      is present in all partially purified fractions. This activity is tightly
      associated with other nuclear factors and proteins, which resulted in
      differential fractionation of this activity on ion exchange columns. One nuclear
      factor associated with this activity is identified as RNA. Another nuclear
      protein, proliferating cell nuclear antigen (PCNA) is also associated with this
      enzyme. Glycosylic removal of 5-meC from DNA by this activity could be involved
      in the regulation of transcription, replication, differentiation, and development
      through resultant hypomethylation of DNA.

PMID- 10967553
TI  - Extracellular matrix and nuclear localization of beta ig-h3 in human bladder
      smooth muscle and fibroblast cells.
AB  - The extracellular matrix (ECM) plays an essential role in bladder structure and
      function. In this study, expression of beta ig-h3, a recently identified
      extracellular matrix protein, was investigated in human bladder tissue, and human
      bladder smooth-muscle (SMC) and fibroblast cells in vitro. SMCs secreted greater
      than three times the level of this protein compared with fibroblasts. The
      relative levels of beta ig-h3 mRNA in the two cell types reflected the protein
      expression. Immunohistochemical analysis demonstrated protein deposition in the
      ECM as well as cytoplasmic localization and, unexpectedly, nuclei. Anti-beta ig
      h3 antibodies also stained the matrix surrounding the detrusor SMCs and nuclei of
      bladder fibroblasts, SMCs, and urothelium in intact bladder tissue. Western blot
      analyses of medium and matrix fractions obtained from cells in vitro revealed
      protein of approximately 70-74 kDa, whereas nuclear extracts contained a 65-kDa
      reactive protein band. We propose that although this protein is a structural
      component of bladder ECM, its nuclear localization suggests that it has other
      regulatory and/or structural functions.

PMID- 10967554
TI  - Activation of Src kinase in skeletal muscle cells by 1, 1,25-(OH(2))-vitamin D(3)
      correlates with tyrosine phosphorylation of the vitamin D receptor (VDR) and VDR
      Src interaction.
AB  - The rapid effect of 1 alpha,25(OH(2))-vitamin D(3) [1 alpha, 25(OH(2))D(3)] on
      tyrosine kinase Src and its relationship to the vitamin D receptor (VDR) was
      investigated to further characterize the hormone signaling mechanism in chick
      muscle cells. Exposure of cultured myotubes to 1 alpha,25(OH(2))D(3) caused a
      time-dependent increase in Src activity, which was evident at 1 min (one-fold)
      and reached a maximum at 5 min (15-fold). Immunoblotting with anti
      phosphotyrosine antibody of immunoprecipitated Src showed that the hormone
      decreased Src tyrosine phosphorylation state with maximal effects at 5 min. Using
      a database for protein consensus motifs we found a putative tyrosine
      phosphorylation site (amino acids 164-170: KTFDTTY) within the primary sequence
      of the chick VDR. When the myotube VDR was immunoprecipitated it appeared onto
      SDS-PAGE gels as a single band of 58 kDa recognized by an anti-phosphotyrosine
      antibody. Prior treatment of cells with (1)alpha,25(OH(2))D(3) significantly
      increased tyrosine phosphorylation of the VDR (two- to three-fold above basal
      levels). In agreement with Src being a SH2-domain containing protein involved in
      recognition of tyrosine-phosphorylated targets, immunoprecipitation with anti-Src
      antibody under native conditions followed by blotting with anti-VDR antibody, or
      using the antibodies in inverse order, showed that the VDR co-precipitates with
      Src, thus indicating the existence of a VDR/Src complex. Stimulation with the
      cognate VDR ligand significantly increased formation of the complex with respect
      to basal conditions. These results altogether provide the first evidence to date
      for 1 alpha,25(OH(2))D(3) activation involving Src association to tyrosine
      phosphorylated VDR.

PMID- 10967555
TI  - Effects of selenite on estrogen receptor-alpha expression and activity in MCF-7
      breast cancer cells.
AB  - To determine whether selenite has estrogen-like activities, the effects of this
      compound on estrogen receptor-alpha (ER-alpha) and other estrogen-regulated genes
      were measured in the human breast cancer cell line MCF-7. Treatment of cells with
      1 uM of sodium selenite resulted in a 40% decrease in the amount of estrogen
      receptor-alpha and in a parallel decrease of 40% in ER-alpha mRNA. Progesterone
      receptor concentration increased 2.6-fold and pS2 mRNA increased 2.4-fold after
      selenite treatment. The induction of progesterone receptor and pS2 was blocked by
      the anti-estrogen ICI-182,780. In transient co-transfection experiments of Wild
      type ER-alpha and an estrogen response element-reporter construct, selenite
      stimulated CAT activity. In binding assays, selenite blocked the binding of
      estradiol to ER-alpha (K(i) = 23 +/- 17 nM, n = 3) suggesting that this compound
      interacts with the hormone binding domain of the receptor. To determine whether
      interaction of selenite with the hormone binding domain results in receptor
      activation, COS-1 cells were transiently co-transfected with the chimeric
      receptors GAL-ER, which contains the hormone binding domain of ER-alpha and the
      DNA binding domain of the transcription factor GAL4, and a GAL4-responsive CAT
      reporter gene. Treatment of cells with estradiol or selenite resulted in a three-
      to five-fold increase in CAT activity. The effects of selenite on the chimeric
      receptor were blocked by the antiestrogen, suggesting that selenite activates ER
      alpha through an interaction with the hormone binding domain of the receptor.
      Transfection assays with ER-alpha mutants identified C381, C447, H524, and N532
      as interaction sites of selenite with the hormone binding domain.

PMID- 10967556
TI  - delta-Ca(2+)/calmodulin-dependent protein kinase II expression pattern in adult
      mouse heart and cardiogenic differentiation of embryonic stem cells.
AB  - delta-isoforms of the Ca(2+)/calmodulin-dependent protein kinase type II (CaMKII)
      are considered to substantially influence cardiac functions. However, no data
      exist on the expression of these isoforms in the mouse heart. We analyzed the
      transcript pattern of non-neuronally expressed delta-isoforms in heart and
      skeletal muscle of adult mice by RT-PCR. For members of the delta-CaMKII subclass
      with both variable domains (subclass II), weak transcriptional expression of
      isoforms delta(2) and delta(3) was found in the heart. In skeletal muscle no
      delta(3)-specific transcript was detectable. In cardiac tissue, stronger signals
      result from amplifications of delta(9) and from members of the subclass I lacking
      the second variable domain. Western blotting was performed using a subclass II
      specific antibody. In murine cardiac and skeletal muscle tissue a delta-CaMKII
      protein pattern was obtained similar to that described for rat. To gain insight
      into the expression of delta-CaMKII during the earliest steps of cardiogenic
      differentiation, we analyzed the transcript pattern of murine embryonic stem cell
      derived cardiomyocytes in various differentiation stages. Reproducible RT-PCR
      signals could be obtained for delta(6) and delta(10), both belonging to the delta
      CaMKII subclass I. Transcripts for delta(6) were ubiquitously expressed, whereas
      transcripts for delta(10) were detectable in increasing amounts after 7-10 days
      of the onset of cardiogenic differentiation. Our results point to a
      differentiation-dependent expression of the two delta-CaMKII subclasses, and also
      to differences in the expression of individual members of subclass I during the
      early stages of cardiogenic differentiation.

PMID- 10967557
TI  - Extracellular glucose influences osteoblast differentiation and c-Jun expression.
AB  - Insulin dependent diabetes mellitus, marked by high blood glucose levels and no
      insulin secretion, is associated with decreased bone mass and increased fracture
      rates. Analysis of bone histology suggests that osteoblast phenotype and function
      are influenced by diabetes. To determine if elevated extracellular glucose levels
      could directly influence osteoblast phenotype we treated mouse osteoblasts, MC3T3
      E1 cells, with 22 mM glucose and analyzed osteoblast gene expression. Collagen I
      mRNA levels significantly increased while osteocalcin mRNA levels decreased 24 h
      after the addition of glucose. Expression of other genes, actin, osteopontin, and
      histone H4, was unaffected. Effects on collagen I expression were seen as early
      as 1 h after treatment. c-Jun, an AP-1 transcription factor involved in the
      regulation of osteoblast gene expression and growth, was also modulated by
      glucose. Specifically, an increase in c-jun expression was found at 1 h and
      maintained for 24 h following glucose treatment. Treatment of osteoblasts with an
      equal concentration of mannitol completely mimicked glucose treatment effects on
      collagen I and c-jun expression, demonstrating that osmotic stress rather than
      glucose metabolism is responsible for the effects on osteoblast gene expression
      and phenotype. Additional studies using staurosporine and Ro-31-8220 demonstrate
      that protein kinase C is required for the glucose up regulation of collagen I and
      c-jun. Taken together, our results demonstrate that osteoblasts respond to
      increasing extracellular glucose concentration through an osmotic response
      pathway that is dependent upon protein kinase C activity and results in
      upregulation of c-jun and modulation of collagen I and osteocalcin expression.

PMID- 10967558
TI  - Tyrosine phosphorylation and cellular redistribution of ezrin in MDCK cells
      treated with pervanadate.
AB  - Ezrin is a key protein in membrane-cytoskeleton interaction and is expressed
      primarily in actin-rich surface projections. Activation in protein tyrosine
      phosphorylation apparently regulates the structure and function of ezrin. In this
      study, we found that pervanadate (PV, the complexes of vanadate with hydrogen
      peroxide) caused an increase in tyrosine phosphorylation of ezrin and affected
      its cellular redistribution. Treatment of Madin-Darby canine kidney (MDCK) cells
      with pervanadate resulted in a dramatically increased tyrosine phosphorylation of
      ezrin within two to five min and the level reached the maximum after 60 min. This
      was accompanied by an alteration in the subcellular distribution of ezrin.
      Immunofluorescence and scanning laser confocal microscopy analysis revealed that,
      after PV stimulation, ezrin was redistributed from cytosol to the apical and
      lateral membrane domains. This occurred within five min, and more obvious
      redistribution to the lateral membrane domain was observed after 30 min.
      Furthermore, immunoblotting of ezrin in cell fractionation experiments showed
      that, in PV-treated MDCK cells, cytosolic ezrin was translocated to the membrane
      fraction, while there was no change in the level of ezrin associated with the
      actin-cytoskeleton. Therefore, cytoplasmic signaling may result in activation of
      ezrin in tyrosine phosphorylation, which is induced by PV stimulation. These
      results suggest that ezrin has qualities that might play a role in modulation of
      cell shape and adhesion.

PMID- 10967559
TI  - The roles of matrix molecules in mediating chondrocyte aggregation, attachment,
      and spreading.
AB  - The most abundant macromolecules in cartilage are hyaluronan, collagen, aggrecan,
      and link protein, which are believed to play roles in maintaining a unique three
      dimensional network for a functional joint. This study was designed to
      investigate the roles of the major extracellular molecules in mediating
      chondrocyte-matrix interactions. We employed specific approaches to remove
      components individually or in combination: hyaluronan was digested with
      hyaluronidase; type II collagen was digested with collagenase; aggrecan
      expression was inhibited with antisense and beta-xyloside approaches; and link
      protein expression was inhibited with antisense oligonucleotides. Digestion of
      hyaluronan induced chondrocyte attachment to tissue culture plates, collagen
      coated plates, and fibroblast-like chondrocyte cultures, and induced chondrocyte
      aggregation. Treated chondrocytes exhibited a fibroblast-like morphology, and the
      effects of hyaluronidase were dose-dependent. Conversely, the effect of
      collagenase on chondrocyte adhesion and aggregation was far less pronounced.
      Treatment with Arg-Gly-Asp peptide inhibited chondrocyte-collagen interaction.
      Chondrocyte attachment was enhanced by antisense oligonucleotides complementary
      to aggrecan and link protein and by beta-xyloside treatment. Nevertheless,
      hyaluronan seems to predominate over the other molecules in mediating chondrocyte
      matrix interactions.

PMID- 10967560
TI  - Membrane signalling and progesterone in female and male osteoblasts. I.
      Involvement Of intracellular Ca(2+), inositol trisphosphate, and diacylglycerol,
      but not cAMP.
AB  - Bone is a target tissue of progestins, but the mechanisms by which they act are
      still unclear. We examined the early (5-60 s) effects of progesterone and
      progesterone covalently bound to BSA (P-CMO BSA), which does not enter the cell,
      on the cytosolic free Ca(2+) concentration ([Ca(2+)]i) and the formation of
      inositol 1,4,5 trisphosphate (InsP3) and diacylglycerol (DAG) in confluent female
      and male rat osteoblasts. P-CMO BSA like free progesterone increased [Ca(2+)]i
      via Ca(2+) influx through L-type Ca(2+) channels and Ca(2+) mobilization from the
      endoplasmic reticulum. Both progestins increased InsP(3) and DAG formation within
      10 s, and the increase was blocked by phospholipase C inhibitors (neomycin and U
      73122). Progesterone and P-CMO BSA mobilized calcium from the endoplasmic
      reticulum via the activation of a phospholipase C linked to a pertussis toxin
      insensitive G-protein in both osteoblast types, and this process was controlled
      by protein kinase C. Neither progestin had any effect on cAMP formation in male
      and female osteoblasts. The membrane effects were not blocked by a progesterone
      nuclear antagonist. They were independent of the concentration of nuclear
      receptors and not linked to gender. Thus, progesterone appears to act in female
      and male rat osteoblasts via unconventional cell-surface receptors which belong
      to the class of membrane receptors coupled to phospholipase C via a pertussis
      toxin-insensitive G-protein. The bifurcating pathways leading to the formation of
      InsP(3) and DAG may provide a certain flexibility in controlling cell responses,
      both by their nature and by their rates of formation and degradation.

PMID- 10967561
TI  - Rapid achievement of complete donor chimerism and low regimen-related toxicity
      after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic
      transplantation.
AB  - Between August 1998 and July 1999, 21 patients received a novel protocol of
      reduced conditioning with fludarabine, carmustine and melphalan (FBM) followed by
      matched-related allogeneic peripheral blood stem cell transplantation (PBSCT) in
      a prospective multi-center phase I/II study. Cyclosporin A and 'mini
      methotrexate' were used for GVHD prophylaxis. Patients were included because of
      age, advanced disease, previous transplantation or co-morbidity. Hematopoietic
      engraftment after allogeneic transplantation was rapid with a median white blood
      count (WBC) >1 x 10(9)/l on day +11 (range 10-17) and a median platelet count >20
      x 10(9)/l on day +13 (range 9-36). Donor chimerism was complete in 16/21 (76%)
      patients at all time points during follow-up and mixed at least on one occasion
      in 5/21 (24%) patients. The conditioning regimen was well tolerated with low
      toxicity even in previously transplanted patients. Thirteen patients (62%)
      developed acute GVHD grades II-IV. Nineteen out of 21 patients achieved complete
      (CR, n = 15) or partial remission (PR, n = 4) with a median patient follow-up of
      354+ days (range 258-577) for patients alive. The reduced intensity protocol FBM
      is feasible with rapid engraftment, early achievement of complete donor
      chimerism, low toxicity, especially in heavily pretreated patients, and good
      response rates in advanced disease patients.

PMID- 10967562
TI  - High rate of secondary viral and bacterial infections in patients undergoing
      allogeneic bone marrow mini-transplantation.
AB  - New approaches using nonmyeloablative-conditioning regimens have been developed
      to cause minimal procedure-related toxicity. Such novel therapeutic options are
      being explored with good preliminary results concerning feasibility and
      engraftment. However many aspects remain under-evaluated, and few data are
      available about viral and nonviral infections after these highly
      immunosuppressive regimens. We present our preliminary data on 21 patients
      receiving a highly immunosuppressive conditioning strategy, focusing on early
      infectious complications. Early viral infections before day 45, especially CMV,
      occurred at a high rate (65%). Furthermore, 33% of patients presented with late
      bacterial infections (predominately gram negative) although they were not
      neutropenic compared to conventional conditioning regimens. Although there is
      presently real interest in these new conditioning regimens which result in
      reduced immediate transplant-related mortality, it is important that
      investigators be aware of these pitfalls which may secondarily increase
      transplant toxicity. Further studies are needed to confirm these findings.

PMID- 10967563
TI  - High-dose chemotherapy (CTM) for breast cancer.
AB  - We designed and implemented a new mitoxantrone-based high-dose chemotherapy
      regimen to minimize pulmonary injury (seen in carmustine-based regimens) in
      patients with breast cancer. One hundred and ninety-one breast cancer patients
      (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose
      chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4
      days (cyclophosphamide (6 g/m2), thiotepa (600 mg/m2), and mitoxantrone (24-60
      mg/m2)) followed by autologous hematopoietic stem cell rescue. Stage II/III
      patients received chest wall radiation and tamoxifen (if hormone-receptor
      positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA
      patients with 10 or more involved axillary lymph nodes (n = 80) was 62 +/- 12%.
      Hormone receptor-positive patients with 10 or more nodes did significantly better
      than negative patients. The EFS for stage IIIB patients at 5 years was 44 +/-
      19%; for stage IV patients at 5 years was 17 +/- 10%. Stage IV patients achieving
      complete response in viscera and/or soft tissue prior to CTM did significantly
      better than those achieving a partial response. There were six (3%) treatment
      related deaths including two due to diffuse alveolar hemorrhage. There were no
      episodes of delayed interstitial pneumonitis. There were six severe cardiac
      events in 91 patients (6.6%) but none after instituting mitoxantrone dose
      adjustment in the final 100 patients. We conclude that CTM is associated with a
      low treatment-related mortality and little pulmonary toxicity. CTM produces
      excellent outcomes in stage II/IIIA patients with 10 or more involved axillary
      lymph nodes.

PMID- 10967564
TI  - Clinical and economic comparison of allogeneic peripheral blood progenitor cell
      and bone marrow transplantation for acute lymphoblastic leukemia in children.
AB  - There is limited experience in the use of peripheral blood progenitor cells
      (PBPC) for allogeneic transplantation in children. In the present study we
      compared engraftment kinetics, incidence of acute and chronic graft-versus-host
      disease (GVHD) and the outcome and economic costs of allogeneic PBPCT vs BMT in
      children with ALL in a single institution. All children were transplanted in
      complete remission (CR) with a similar conditioning regimen and the same GVHD
      prophylaxis. Patients undergoing PBPCT achieved myeloid and platelet engraftment
      before patients undergoing BMT (P < 0.001). Platelet recovery was faster for the
      PBPCT group (P < 0.014 for 50 x 10(9)/l and P < 0.039 for 100 x 10(9)/l).
      Incidence and severity of acute and chronic GVHD were similar in both groups
      (acute grade 1-2: 9/13 for PBPCT vs 9/11 for BMT; chronic GVHD: 5/12 for PBPCT vs
      3/8 for BMT). Hospital stay was shorter for the PBPCT than for the BMT group
      (28.8 days vs 42.9 days, respectively) and the PBPCT group used less clinical
      resources, resulting in overall lower cost for PBPCT (US $14,046) compared to BMT
      (US $19,840). There was no statistically significant difference in DFS between
      PBPCT and BMT (68.4% vs 50%, respectively).

PMID- 10967565
TI  - Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution
      after allogeneic bone marrow transplantation in chronic myelogenous leukemia--a
      single center experience on 160 patients.
AB  - A retrospective single center study was performed on 516 trephine biopsies
      derived from 160 patients with stable phase Ph+-CML and allogeneic BMT. Following
      morphometric quantification of reticulin-collagen fibers we tried to elucidate
      (1) the dynamics of bone marrow fibrosis in the post-transplant period; and (2)
      the influence of manifest myelofibrosis on relevant engraftment parameters. An
      evaluation of fiber density at standardized endpoints after BMT was carried out
      on a selected cohort of 124 patients (399 biopsy specimens). A manifest
      myelofibrosis (more than a three-fold increase compared to the normal fiber
      content) before BMT was found in 26% of our patients. Concentrating on bone
      marrow areas with reconstituting hematopoiesis, several findings emerged.
      Pretransplant myelofibrosis was associated with an initial regression following
      BMT, but insidiously recurred in the areas of regenerating hematopoiesis or
      developed in a few patients without increased pregraft fibers during the post
      transplant period (mean observation time more than 4 months). Severe acute GVHD
      (grades III and IV) was significantly correlated with a greater amount of
      reticulin fibers in the early post-transplant period (9 to 30 days after BMT).
      Regarding engraftment parameters, a significant delay was detectable in the time
      to achieve transfusion independence for the patients with manifest myelofibrosis
      compared to those without pre-transplant fiber increase.

PMID- 10967566
TI  - Blood stem cell collections in multiple myeloma: definition of a scoring system.
AB  - The purpose of the study was to identify factors that could predict good yields
      of peripheral blood stem cells (PBSC) in multiple myeloma (MM). Fifty-one MM
      patients, nine with refractory disease and 42 in plateau phase, were mobilized
      with high-dose cyclophosphamide (HD-Cy) at 4 g/m2 followed by granulocyte colony
      stimulating factor (G-CSF) 5 microg/kg/day. Clinical and laboratory parameters at
      the time of mobilization were analyzed for correlations with the number of CD34+
      cells collected, with the colony-forming unit granulocyte-macrophage (CFU-GM)
      count, and the mononuclear cell (MNC) count. In univariate analysis, low WBC
      count, low platelet count, prior exposure to melphalan, and an interval >6 months
      from the start of treatment correlated with poor yields of CD34+ cells. Low
      platelet count, prior exposure to melphalan or to radiotherapy, and an interval
      >6 months from the start of treatment were associated with a low CFU-GM count. On
      the basis of these data, we defined a scoring system able to predict the yield of
      the mobilizing procedure. According to this system, the presence of more than one
      risk factor (low WBC and platelet counts, prior exposure to melphalan, interval
      from first chemotherapy >6 months) was predictive of insufficient collections
      when a conventional combination of mobilizing measures are used.

PMID- 10967567
TI  - Sequential analysis of HLA-C-specific killer cell inhibitory receptor (CD158b)
      expressing peripheral blood mononuclear cells during chronic graft-versus-host
      disease.
AB  - We have sequentially investigated the expression of natural killer cell
      inhibitory receptors (KIRs) for HLA-C (CD158b) on peripheral blood mononuclear
      cells (PBMC) in three patients with extensive chronic graft-versus-host disease
      (cGVHD) after allogeneic bone marrow transplantation (alloBMT). Clinical symptoms
      of cGVHD were not cured and worsened in the first patient whose CD158b-positive
      cells increased to 18.5% during cGVHD and decreased to 9.4% at 8 months after
      transplantation. On the other hand, cGVHD was cured and did not relapse in the
      second patient whose CD158b-positive cells increased up to 45.9% during cGVHD and
      sustained 19.4% at 8 months after transplantation. In contrast, CD158b-positive
      cells were less than 10% during the course of cGVHD in the third patient, and her
      cGVHD did not respond to treatment. Therefore, it appears that chronic
      allostimulation augments the expansion of CD158b-positive cells and these
      expanded CD158b-positive cells may have some role in the control of alloresponse
      in some patients.

PMID- 10967568
TI  - Tuberculosis after hematopoietic stem cell transplantation: incidence, clinical
      characteristics and outcome. Spanish Group on Infectious Complications in
      Hematopoietic Transplantation.
AB  - A national survey of tuberculosis after hematopoietic stem cell transplant (SCT)
      was undertaken to study incidence, clinical presentation and outcome. Twenty
      confirmed cases were found among 8,013 patients (eight in 5,147 autologous and 12
      in 2,866 allogeneic SCT). The estimated incidence in cases/10(5) patients/year
      (95% CI) was 101 (56.5-145) for the whole group, 71.1 (21.8-120) in autologous
      and 135.6 (58.9-212) in allogeneic transplants. Compared with the general
      population, tuberculosis was more frequent after allogeneic (RR 2.95) but not
      after autologous SCT. Tuberculosis after SCT is a late infection (median 324 days
      post transplant), predominately affects the lungs (80% of the cases), appears to
      respond well to treatment but has a high mortality (25%) in allogeneic
      recipients. It can also complicate the post-transplant management as
      antituberculosis drugs frequently decrease the serum levels of cyclosporine
      causing an aggravation of GVHD. Graft-versus-host disease, corticosteroid
      treatment and total body irradiation appear to be associated with tuberculosis in
      allogeneic recipients. No obvious factors were associated with tuberculosis in
      autologous transplants. Finally, we found that the published literature on
      tuberculosis after solid and SCT has overestimated its incidence due to the
      direct translation of tuberculosis frequency into incidence.

PMID- 10967569
TI  - Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic
      and autologous stem cell transplant recipients.
AB  - The incidence and aetiology of acute diarrhoea in 60 adult allogeneic or
      autologous stem cell transplant (SCT) recipients was determined in a prospective
      study. Stool specimens were obtained prior to SCT and on days +20, +40, +60 and
      +100 post transplant. Microbiological evaluation was performed for pathogenic
      bacteria, fungi, parasites and viruses. Forty-seven patients were evaluable of
      whom 31 had a total of 48 acute diarrhoeal episodes. Diarrhoea occurred in 79% of
      allogeneic and 47% of autologous SCT recipients (P < 0.05). Intestinal infections
      were found in three of 48 (6%) diarrhoeal episodes. Clostridium difficile with
      positive toxin was cultured twice and one stool specimen was positive for
      cryptosporidium. Intestinal pathogens were identified in 13 out of 172 stool
      specimens from asymptomatic patients and included: rotavirus (4), adenovirus (3),
      C. difficile, toxin positive (2), and others (4). Graft-versus-host disease was
      confirmed by biopsy in two of 36 episodes of diarrhoea in allogeneic patients,
      and in three patients a relationship between reactivation of cytomegalovirus and
      diarrhoea was suspected. In 40 of 48 (83%) episodes of diarrhoea no clear
      aetiology could be found.

PMID- 10967570
TI  - Adenovirus infections following haematopoietic cell transplantation: is there a
      role for adoptive immunotherapy?
AB  - Adenovirus has been recognised as an important pathogen in BMT recipients,
      especially in patients with GVHD and those receiving T cell-depleted allografts.
      We report adenovirus infections from an ongoing surveillance study in four
      patients after a non-myeloablative transplant and their improved outcome
      following withdrawal of immunosuppression in two patients and donor lymphocyte
      infusion for relapsed disease in the others. We discuss the control of adenovirus
      infections following immune manipulations and the feasibility of adoptive
      immunotherapy for post-transplant adenovirus infections.

PMID- 10967571
TI  - Assessment of cardiotoxicity during haemopoietic stem cell transplantation with
      plasma brain natriuretic peptide.
AB  - Cardiac failure is a known complication of haemopoietic stem cell transplantation
      (HSCT) and is often difficult to diagnose as patients may have multiple medical
      problems. Since brain natriuretic peptide (BNP) is largely a hormone of cardiac
      ventricular origin and is released early in the course of ventricular
      dysfunction, we have examined the value of serial plasma BNP levels for detecting
      cardiac failure in patients undergoing cytotoxic conditioning for HSCT. Fifteen
      patients undergoing HSCT were evaluated (10 undergoing autologous HSCT; five
      undergoing allogeneic HSCT). BNP was measured by radioimmunoassay prior to
      therapy and weekly for 5 weeks. Seven patients had a significant rise in BNP
      level (above a previously established threshold of 43 pmol/l associated with
      cardiac failure), occurring 1-4 weeks post commencement of conditioning. In three
      of these patients, cardiac failure was subsequently diagnosed clinically 3, 9 and
      23 days after a BNP level of 43 pmol/l had been detected. These three patients
      had the highest peak BNP levels for the group and in each case elevation in BNP
      level occurred for a period exceeding 1 week. Although numbers were relatively
      small, a BNP >43 pmol/l was significantly associated with the inclusion of high
      dose cyclophosphamide in the preparative regimen (P = 0.02). BNP levels showed no
      relationship to febrile episodes. In conclusion, these results show that plasma
      BNP may be used as a marker for early detection of cardiac dysfunction in
      patients undergoing HSCT, particularly if levels are increased for periods
      exceeding 1 week. Measurement of BNP during HSCT may be helpful in patients at
      risk of cardiac failure, in complex clinical situations and in monitoring the
      cardiotoxicity of preparative regimens.

PMID- 10967572
TI  - Bleeding risk and platelet transfusion refractoriness in patients with acute
      myelogenous leukemia who undergo autologous stem cell transplantation.
AB  - Therapy for acute myelogenous leukemia can be complicated by alloimmunization to
      histocompatibility antigens (HLA), with resultant refractoriness to platelet
      transfusions. Autologous peripheral blood or bone marrow stem cell
      transplantation (referred here collectively as 'autoBMT') is emerging as a
      standard consolidative strategy in acute myelogenous leukemia (AML). We had noted
      life-threatening bleeding associated with platelet transfusion refractoriness
      following autoBMT; we therefore retrospectively analyzed 39 AML patients for this
      complication following BMT. All patients received high-dose chemoradiotherapy,
      followed by infusion of allogeneic sibling donor (n = 12, alloBMT) or autologous
      (n = 27, autoBMT) stem cells. HLA alloimmunization was assessed if patients were
      suspected of immune refractoriness to random donor platelet transfusions. Within
      100 days of stem cell infusion, one of three alloBMT and six of 12 autoBMT
      recipients tested were HLA alloimmunized (not statistically significant, NS).
      Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding,
      which contributed to their demise while still in remission (P < 0.001). Increased
      platelet requirements in HLA alloimmunized autoBMT recipients were observed
      between days 61 and 100 post-BMT, at a median of 211 platelet transfusions vs 0
      in non-alloimmunized autoBMT patients (P < 0.01) and 17 in alloBMT patients. Our
      data suggest that platelet transfusion refractoriness, when associated with HLA
      alloimmunization, is a risk factor for increased platelet transfusion
      requirements, delayed bleeding, and poor outcome following autoBMT for AML.

PMID- 10967573
TI  - Myelodysplasias and leukemias after autologous stem cell transplantation for
      lymphoid malignancies.
AB  - The incidence of secondary myelodysplastic syndromes and acute leukemia (MDS/AL)
      was reported for 395 patients autografted for Hodgkin's disease (HD) (n = 96) and
      non-Hodgkin's lymphoma (NHL) (n = 299) between 1987 and 1998. Eleven patients
      developed secondary MDS/AL (crude rate at 2.8%) including two lymphoblastic AL
      cases. The mean time of occurrence was at 32 months after autologous stem cell
      transplantation (ASCT) and 71 months after diagnosis. The estimated actuarial
      incidence at 10 years was at 6.3% (+/-4%). Karyotyping revealed complex
      chromosomal aberrations in only one patient, and two translocations [t(8;21) and
      t(8;16)]. No features of topoisomerase II inhibitor-related leukemia were found.
      Only one patient had received ASCT in first remission. The remaining 10 patients
      had received multiple courses of chemotherapy before stem cell collection and
      four had relapsed after ASCT and before the occurrence of secondary MDS/AL. Five
      of 11 patients had received localized radiotherapy and five others received TBI
      in their conditioning regimen. Ten patients died despite chemotherapy and/or
      supportive care and only one patient is alive and well after genoidentical
      allogeneic transplantation. We suggest a cumulative leukemogenic role of pre-ASCT
      radiation and chemotherapy in the occurrence of these secondary MDS/AL more than
      the high-dose therapy itself.

PMID- 10967575
TI  - High-dose melphalan and allogeneic peripheral blood stem cell transplantation for
      treatment of early relapse after allogeneic transplant.
AB  - Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a
      poor prognosis. We studied the use of melphalan 180 mg/m2 followed by allogeneic
      peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing
      after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were
      AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast
      crisis (n = 1). Eight patients were beyond first relapse and none were in
      remission. The median time from previous transplant to relapse was 146 days
      (range 66-206). The melphalan dose was 90 mg/m2 intravenously on days -4 and -3
      with PBSC infusion on day 0. GVHD prophylaxis consisted of cyclosporine and
      methylprednisolone. The median time to an absolute neutrophil count >0.5 x
      10(9)/l and to a platelet count >20 x 10(9)/l was 11 and 13 days, respectively.
      All engrafting patients (n = 8) had 100% donor cells. Two patients died before
      day 30, but no other grade 3 or 4 toxicity occurred. Acute GVHD grades II-III
      occurred in two subjects, and chronic GVHD in four. Seven patients achieved CR,
      but relapsed at a median of 116 days (range 56-614). Leukemia was the cause of
      death in eight patients. Median survival was 149 days (range 6-614). This
      treatment produced responses in the majority of this poor prognosis group.
      However, durable remissions were not observed, and new treatments to consolidate
      the responses achieved in this setting are needed. This regimen could be
      considered for short-term disease control to facilitate donor lymphocyte infusion
      based immunotherapy or other measures to prevent disease recurrence.

PMID- 10967574
TI  - Prognostic value of hematopoietic chimerism in patients with acute leukemia after
      allogeneic bone marrow transplantation: a prospective study.
AB  - Hematopoietic chimerism as a predictive marker for the relapse of acute leukemia
      after allogeneic BMT was evaluated in a prospective study. Monthly assays of
      hematopoietic chimerism were performed from peripheral blood samples by PCR
      amplification of short tandem repeats or amelogenin loci. Between December 1997
      and June 1999, 33 patients enrolled and 30 were evaluable (two early deaths, one
      lack of informative bands for chimerism evaluation). There were 14 male and 16
      female patients (15 AML and 15 ALL) with a median age of 31 years (range 16-46).
      Mixed chimerism (MC) was observed at least once in 14 of 30 patients (47%). There
      was no significant difference between 14 patients who showed MC (MC group) and 16
      patients who did not show MC (complete chimerism (CC) group) in terms of age,
      sex, disease status at BMT, donor type, and the number of bone marrow cells
      infused. There was no significant difference in the neutrophil and platelet
      engraftment rates between the two groups. After a median follow up of 10.9 months
      (range 4.3-22.4), five patients in the CC group and two patients in the MC group
      relapsed (P = 0.27). All five patients who relapsed in the CC group maintained CC
      up to 1 month prior to clinical relapse. Our study demonstrated that the patients
      who showed MC post BMT did not have higher risk of relapse of acute leukemia when
      compared to patients who did not show MC. Sensitive PCR-based assays for
      hematopoietic chimerism applied on a monthly basis after allogeneic BMT could not
      predict relapse of acute leukemia.

PMID- 10967576
TI  - Successful large volume leukapheresis on a small infant allogeneic donor.
AB  - We successfully performed a hematopoietic stem cell apheresis on the smallest
      allogeneic donor reported to date, a 6.1 kg female. After placement of a dialysis
      catheter in the left femoral vein, the COBE Spectra was primed with one unit of
      paternal whole blood. Heparin and anticoagulant citrate dextrose, solution A (ACD
      A) were slowly administered to the patient. Ionized calcium levels were checked
      hourly and calcium gluconate was given for hypocalcemia. Coagulation parameters
      were checked throughout the procedure. We collected 4.4 x 10(6) CD34+ cells/kg
      (recipient). The donor tolerated the procedure well and was discharged the
      following day. Five months later, the child manifests no obvious late effects.

PMID- 10967577
TI  - Hyperammonemia after high-dose chemotherapy and stem cell transplantation.
AB  - We report a patient with multiple myeloma who suffered from hyperammonemia after
      a second stem cell autograft. This syndrome is not well known but is associated
      with a high mortality rate. Considering the possibility of this diagnosis in
      patients developing confusion and neurological degradation with respiratory
      alkalosis after intensive chemotherapy, could allow earlier treatment and perhaps
      improved survival. Possible mechanisms and potential therapies are discussed.
      With rapid recognition and treatment of the syndrome, the patient fully
      recovered. One and a half years later, she is still alive and well, on interferon
      for persisting myeloma.

PMID- 10967578
TI  - Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV
      reactivation with cidofovir.
AB  - Hemorrhagic cystitis (HC) is a common complication following high-dose
      chemotherapy and bone marrow transplantation, and the treatment of virus
      associated HC remains to be optimized. This is the first report on the successful
      use of cidofovir in a patient with HC and polyoma viruria concomitant with CMV
      reactivation after allogeneic BMT. Treatment led to a significant decrease in
      viruria and to sustained suppression of CMV reactivation. Administered with
      probenecid and hydration, cidofovir was well tolerated, and there were no side
      effects.

PMID- 10967579
TI  - Re-mobilization of peripheral blood progenitor cells within a short time interval
      fails to achieve effective progenitor cell yields.
AB  - We report the case of a healthy donor who was mobilized for the purpose of
      performing an unrelated donor transplantation with subcutaneous injections of rhG
      CSF. Because of accidental loss of progenitors, 3 days after completing the first
      collection, the donor was mobilized again with rhG-CSF, and progenitors were
      collected. While a similar increase in the pre-apheresis leukocyte count was
      observed in both procedures, fewer mononuclear cells were mobilized during the
      second rhG-CSF course, resulting in a poor CD34+ yield. These data suggest that
      an 8-day interval between commencement of rhG-CSF mobilizations is insufficient
      to predict an efficient collection of hematopoietic progenitors to ensure
      engraftment after bone marrow transplantation.

PMID- 10967580
TI  - Treatment of leukemic relapse following unrelated umbilical cord blood
      transplantation with interleukin-2: potential for augmenting graft-versus
      leukemia and graft-versus-host effects with cytokines.
AB  - In comparison to bone marrow, umbilical cord blood has decreased intrinsic immune
      responsiveness allowing transplantation across HLA barriers with lower rates of
      graft-versus-host disease. However, laboratory models have also suggested that
      cord blood may be extremely sensitive to stimulation by cytokines. We report an
      adult recipient of an ex vivo expanded, HLA-mismatched, unrelated cord blood
      transplant who experienced a late extramedullary relapse while still in
      hematologic remission. Despite demonstrating immune tolerance on minimal
      immunosuppressive agents, a brief course of intravenous interleukin-2 resulted in
      rapid, aggressive graft-versus-host and graft-versus-leukemia reactions. This
      case highlights the potential of cytokine immunomodulation following cord blood
      transplantation, but also suggests caution in stimulating these cells.

PMID- 10967581
TI  - Bone marrow transplantation for infantile ceramidase deficiency (Farber disease).
AB  - Infantile ceramidase deficiency (Farber disease) is an uncommon, progressive
      lysosomal storage disease characterized by multiple ceramide-containing nodules
      (lipogranulomata) in the subcutaneous tissue and upper aerodigestive tract,
      painful periarticular swelling, psychomotor retardation, and varying degrees of
      ocular, pulmonary or hepatic involvement. Management of Farber disease has been
      limited to symptomatic supportive care, and few affected infants survive beyond 5
      years of age. We performed an allogeneic bone marrow transplant (BMT) from an HLA
      identical heterozygous sister in a 9.5-month-old female with minimally
      symptomatic Farber disease who received a pre-transplant regimen of busulfan and
      cyclophosphamide. Ceramidase activity in peripheral blood leukocytes increased
      from 6% before transplant to 44% (donor heterozygote level) by 6 weeks after BMT.
      By 2 months after transplant, the patient's subcutaneous lipogranulomata, pain on
      joint motion, and hoarseness had resolved. Despite modest gains in cognitive and
      language development, hypotonia and delayed motor skills persisted. Gradual loss
      of circulating donor cells with autologous hematopoietic recovery occurred; VNTR
      analyses showed 50% donor DNA in peripheral blood cells at 8.5 months after BMT
      and only 1% at 21 months after transplant. Interestingly, leukocyte ceramidase
      activity consistently remained in the heterozygous range despite attrition of
      donor cells in peripheral blood. This novel observation indicates ongoing
      hydrolase production by non-circulating donor cells, possibly in the mononuclear
      phagocytic system, and uptake by recipient leukocytes. Although lipogranulomata
      and hoarseness did not recur, the patient's neurological and neurocognitive
      status progressively declined. She died 28 months after BMT (age 37.5 months)
      with pulmonary insufficiency caused by recurrent aspiration pneumonias.
      Allogeneic BMT improves the peripheral manifestations of infantile ceramidase
      deficiency, but may not prevent the progressive neurological deterioration, even
      when carried out in minimally symptomatic patients.

PMID- 10967582
TI  - Reliability of the interpretation of coronary angiography by the simple visual
      method.
AB  - OBJECTIVE: Evaluation of inter and intraobserver reproducibility of by the visual
      method interpretation of cineangiogram in a clinically based context. METHODS:
      Five interventional cardiologists analyzed 11 segments of 8 coronary
      cineangiograms at a two month apart sessions. The percent luminal reduction by
      the lesions were analyzed by two different classifications: in one (A) the
      lesions were graded in 0% = absent, 1-50% = mild, 51 - 69 = moderate, and > or =
      70% = severe; the other classification (B) was a dichotomic one : <70% =
      nonsignificant and > or = 70%=significant lesions. The agreement were measured by
      the kappa (k) index. RESULTS: Interobserver agreement was moderate for
      classification A (1st measurement, k = 0.36 - 0.63, k m = 0.49; 2nd measurement,
      k = 0.39-0.68, k m = 0.52) and good for classification B (1st measurement, k =
      0.55-0.73, k m = 0.63; 2nd measurement, k = 0.37-0.82, k m = 0.61). Intraobserver
      levels of agreement were k = 0.57-0.95 for classification A and 0.62-1.0 for
      classification B. CONCLUSION: The higher level of reproducibility obtained by
      adopting the dichotomous criteria usually considered for ischemic limits
      demonstrates that in the present clinical context, the reliability of the simple
      visual method is adequate for the identification of patients with clinically
      significant lesions and candidates for myocardial revascularization procedures.

PMID- 10967583
TI  - The effect of siesta in parameters of cardiac structure and in interpretation of
      ambulatory arterial blood pressure monitoring.
AB  - OBJECTIVE: To evaluate the influence of the siesta in ambulatory blood pressure
      (BP) monitoring and in cardiac structure parameters. METHODS: 1940 ambulatory
      arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15
      minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and
      21% of the records indicated that the person had taken a siesta (263 woman, 52+/
      14 years). The average duration of the siesta was 118+/-58 minutes. RESULTS:
      (average +/- standard deviation) The average of systolic/diastolic pressures
      during wakefulness, including the napping period, was less than the average for
      the period not including the siesta (138+/-16/85+/-11 vs 139+/-16/86+/-11 mmHg,
      p<0. 05); 2) pressure loads during wakefulness including the siesta, were less
      than those observed without the siesta); 3) the averages of nocturnal sleep blood
      pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops
      were similar to those in the siesta including wakefulness with and without the
      siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with
      and without the siesta, during the siesta and nocturnal sleep in relation to the
      average obtained in women; 6) patients with a reduction of 0- 5% during the
      siesta had thickening of the interventricular septum and a larger posterior wall
      than those with a reduction during the siesta >5%. CONCLUSION: The siesta
      influenced the heart structure parameters and from a statistical point of view
      the average of systolic and diastolic pressures and the respective pressure loads
      of the wakeful period.

PMID- 10967584
TI  - Peripheral arterial embolism. Report of hospitalized cases.
AB  - OBJECTIVE: We analyzed the frequency of peripheral embolisms, the underlying
      heart disease,triggering factors, the sites of the emboli, and evolution of the
      patients. METHODS: We analyzed 29 cases of peripheral arterial embolism out of a
      total of 20,211 hospitalizations in a cardiology center in the city of Sao Paulo.
      The age was 51.89+/-18.66 years, and 15 were males. RESULTS: Embolism in the
      right lower limb occurred in 18 patients (62.0%),in the left lower 11(37.9%) and
      right upper 3 (10.3%) limbs, and in the left arm (1). Four patients had embolism
      in two limbs. The heart disease, mitral valvar heart disease (9 patients -
      31.0%); infective endocarditis (7- 24.1%); dilated cardiomyopathy (6 - 20.6%);
      ischemic coronary heart disease (6 patients - 20.6%); and one patient with cor
      pulmonale. Atrial fibrillation was observed in 20 patients (68.9%), chronic in 12
      patients (41.3% ) and acute in 8 (27. 5%). All patients with mitral valvar heart
      disease had atrial fibrillation, chronic in 8 patients (88.8%); patients with
      cardiomyopathy and coronary heart disease, 4 in each group had atrial
      fibrillation, acute in 60% of the patients. Patients with infective endocarditis,
      3 had staphylococcus and 2 Gram-negative bacteria. In the follow-up, 2 patients
      (6.8%) required limbs amputation, and 5 (17.2%) died due to embolism. CONCLUSION:
      Most of the time, embolism does not cause permanent complications. Our data
      highlight the importance of anticoagulation for patients acute atrial
      fibrillation in myocardial dysfunction and for patients with chronic atrial
      fibrillation in cases of mitral valvar heart disease to prevent peripheral
      embolism.

PMID- 10967585
TI  - Mortality attributed to myocardial infarction in the male and female population
      of Salvador, BA, between 1981 and 1996.
AB  - OBJECTIVE: To describe according to gender the trend in mortality attributed to
      myocardial infarction (MI) in the population of Salvador, Bahia between 1981 and
      1996. METHODS: This study was on mortality due to MI estimates by period and
      gender of the city of Salvador, Bahia. Data from 1981 to 1996 were stratified by
      quadrienia, and the percentage reduction in death rate due to MI relative to the
      preceding period (PRR) was determined. Comparisons between genders were expressed
      by the male/female death ratio (DR) based on the gender-related PPR. RESULTS: An
      overall increase of approximately 8% was observed in the death rate attributed to
      MI for the period 1985-1988 (89.2/10 5 individuals / year) versus the period 1981
      1984 (82.1/10(5)/ year). In the subsequent periods, overall reductions of 10% and
      20.3% were observed for the periods 1989-1992 and 1993-1996, respectively. For
      men, the PPRs were 11.1 in the period 1989-1992 and 22.7% in the period 1993
      1996. The PPRs in women were lower: 8.6% and 17.4% between 1989 and 1992, and
      1993 and 1996, respectively. Death rate reduction was greater for men than women,
      then the male/female DR decreased from 1.66 in 1981-1984 to 1.35 in 1993-1996.
      CONCLUSION: The results indicate a trend towards a reduction in the death rate
      attributed to myocardial infarction in the city of Salvador from the second half
      of the 1980s onwards, striking in men.

PMID- 10967586
TI  - Congenital atresia of the ostium of the left coronary artery. Diagnostic
      difficulty and successful surgical revascularization in two patients.
AB  - We report two cases of congenital atresia of the ostium of the left coronary
      artery. Case 1: a six-month-old infant presenting with serious cardiac
      insufficiency. A noninvasive diagnosis of dilated myocardiopathy was established
      and the clinical picture was pharmacologically compensated. When the patient was
      nine months of age, a hemodynamic study was performed that revealed congenital
      atresia of the ostium of the left coronary artery; the infant immediately
      underwent a successful anastomosis of the internal mammary artery with the left
      coronary artery. Case 2: an eleven-year-old asymptomatic boy with a history of
      heart murmur from the age of six months on, was referred for surgery with a
      diagnosis of anomalous origin of the left coronary artery from pulmonary trunk. A
      definitive diagnosis of atresia of the left coronary ostium was only established
      during surgery. Successful surgical revascularization with the left internal
      mammary artery, and left ventricular aneurysmectomy were performed.

PMID- 10967587
TI  - Myocardial infarction and subsequent pregnancy.
AB  - We report the case of a 40-year-old woman with 2 previous myocardial infarctions,
      revascularization surgery, and an ongoing pregnancy complicated with preeclampsia
      and fetal hypoxia. Her follow-up performed by a multidisciplinary team made
      possible the birth through cesarean section of a premature infant of the female
      sex with a very low birth weight, but without severe respiratory distress of the
      hyaline membrane disease type. Three months after the delivery, mother and
      daughter were healthy.

PMID- 10967588
TI  - Bilateral carotid endarterectomy combined with myocardial revascularization
      during the same surgical act.
AB  - The best surgical approach for the treatment of patients with severe cerebral
      artery disease and simultaneous serious coronary artery disease still remains
      controversial. In this report we present a case of a 72-year-old female patient
      admitted to the hospital with unstable angina. Triple coronary artery obstructive
      disease and severe bilateral carotid artery stenosis were diagnosed. A combined,
      simultaneous surgical procedure was performed. After total circulatory by-pass
      with a membrane oxygenator, the patient's body temperature was lowered to 32
      degrees C. During the cool-down period, three proximal anastomoses of segments of
      autologous saphenous veins were performed in the ascending aorta. Immediately
      afterwards, bilateral carotid endarterectomy was performed, followed by three
      distal anastomoses to coronary arteries. The patient showed a satisfactory post
      operative outcome. It was concluded that the combination of moderate hypothermia,
      hemodilution with appropriate hemodynamic control, as used in this patient, was
      an effective method of cerebral protection. The simultaneous approach of carotid
      endarterectomy and coronary artery by-pass surgery should be seen as a safe
      option for the treatment of this type of patient.

PMID- 10967589
TI  - A 15-year-old male with progressive muscular dystrophy of the becker type and
      severe heart failure.

PMID- 10967590
TI  - Expression of nitric oxide synthases in the pathophysiology of cardiovascular
      diseases.

PMID- 10967591
TI  - [Poisonous sting by Tityus stigmurus (Scorpiones; Buthidae) in the state of
      Bahia, Brazil].
AB  - The present investigation is a descriptive study regarding the clinical aspects
      of accidents caused by the scorpion Tityus stigmurus in Bahia, Brazil. We
      analyzed 237 confirmed cases treated by the Antivenom Information Centre (CIAVE)
      from 1982 to 1995. Envenomation by T. stigmurus was mainly characterized by local
      symptoms: pain (94.4%), dormancy (30.0%), edema (17.8%), erythema (17.8),
      paresthesia (15.6%) and general manifestations such as headache (4.4%), vomiting
      (4.4%) and sudoresis (3.3%). Most of the envenomation cases were mild (94%) and
      all were successfully cured. Although T. stigmurus venom is not in the pool of
      anti-venom serum (SAE), the absence of lethality and benign nature of the cases
      suggest the efficiency of SAE. With the exception of deaths and systemic
      complications, envenoming gravity was similar to those of Tityus serrulatus.

PMID- 10967592
TI  - Excito-repellency effect of deltamethrin on triatomines under laboratory
      conditions.
AB  - This work demonstrates that deltamethrin in low doses produces an excito
      repellency effect on triatomines, as already observed for mosquitoes. A wooden
      box covered with a cloth impregnated with deltamethrin at doses of 2.5 and 5mg
      ai/m2 was utilized for the experiment. The triatomine species studied were
      Triatoma infestans, Panstrongylus megistus, Rhodnius neglectus and Triatoma
      sordida. Adults were released in one of the sides of the box and their position
      was noted in subsequent periods. The observations were realized on the day the
      cloth was impregnated and subsequently repeated at 30 and 60 days for T. sordida;
      on day 120, the remaining species were included. Insect mortality and attempts at
      flight from the box were also observed. Excito-repellency was evident for all
      species and doses up to day 120. The only species that attempted to fly was P.
      megistus. The excito-repellency effect may be considered as an additional
      advantage to the insecticide power, as it should be able to prevent the
      installation of new colonies by females that fly into the homes, and at the
      moment of the spraying, it should promote the flushing out of triatomines from
      the wall crevices and from other shelters.

PMID- 10967593
TI  - Nested-PCR using MPB64 fragment improves the diagnosis of pleural and meningeal
      tuberculosis.
AB  - Fluids in which Mycobacterium tuberculosis are seldom found, such as pleural and
      cerebrospinal liquids, are good candidates to be studied using PCR techniques. We
      detail our experience with a PCR assay applied to pleural and cerebrospinal
      fluids using the primer MPB64. Seventy three specimens were analyzed: 30 pleural
      fluids (PF), 26 pleural biopsies (PB) and 17 cerebrospinal fluids (CSF). The gold
      standard for the diagnosis of tuberculous meningitis was the positive culture for
      M. tuberculosis in CSF. Tuberculous pleural effusion was diagnosed when cultures
      of PF and/or PB were positive for M. tuberculosis, or the PB histology showed
      granulomas. Our results, compared to the gold standards employed, showed a
      sensitivity of 70%, specificity of 88%, positive predictive value of 82% and
      negative predictive value of 80%. The high specificity of the MPB64 fragment
      while still retaining a good sensitivity makes it very well suited for pleural
      and cerebrospinal tuberculosis diagnosis.

PMID- 10967594
TI  - [Seroprevalence of measles antibodies in a pediatric population from Botucatu,
      Sao Paulo State, Brazil].
AB  - A study of the seroprevalence of measles antibodies was conducted in a population
      of children residing in Botucatu, SP, in order to asses their immunological
      status whether induced by natural infection or by vaccination. A total of 101
      children were studied, all of which had been vaccinated against measles. The
      laboratory tests used to determine the presence of antibodies in the collected
      blood samples were hemagglutination inhibition (HI) and immunoenzymatic assay
      (ELISA). HI results showed that 92.1% of the samples presented antibodies against
      measles. Samples with titers <1:4 when studied by HI were retested by ELISA in
      the same laboratory and only two continued to be negative for measles antibodies.
      Thus, measles antibodies were present in 98% of the serum samples from the
      children studied.

PMID- 10967595
TI  - [Methylmercury human exposure in riverside villages of Tapajos basin, Para State,
      Brazil].
AB  - Evaluation of total human exposure to mercury and methylmercury was effected in
      riverine villages along the Tapajos river and in the metropolitan area of Belem
      city, state of Para, Brazil, by using total mercury and methylmercury
      concentrations in hair samples in 1994 and 1995. It was observed that average
      concentrations of total mercury are in a range from 2 +/- 1 microg/g-1 to 20.5 +/
      12. 1 microg/g-1. While methylmercury average concentration varies from 1. 4 +/-
      0.7 microg/g-1 to 18.5 +/- 11 microg/g-1. These results confirm mercury
      contamination in the Tapajos river and possible appearance of mercury
      intoxication symptoms, and recommends the monitoring of compounds in hair samples
      as well as the need for epidemiological and clinical studies for human health
      prevention and control of mercury intoxication.

PMID- 10967596
TI  - [Tetanus in Brazil: a disease of the elderly?].
AB  - Epidemiological data regarding the age distribution of tetanus in Brazil is
      scarce. This work analyzed the historical evolution of tetanus in Brazil, between
      1980 and 1991, according to the Mortality Information System and established the
      age distribution for this disease. The data used was that provided by FUNASA
      CENEPI, DATASUS and IBGE. Between 1980 and 1991, the coefficient of general
      incidence dropped from 2.6 to 1.0 case per 100,000 inhabitants. There was a
      decline in the mortality coefficients within all the age groups, except in the
      elderly. In the North and South regions, there was an increase in the mortality
      coefficient among the elderly. Infantile tetanus is disappearing, particularly,
      in the developed areas. However, the overall lethality tended to rise in this
      period and, in 1991, it reached 32.5%. In Brazil, tetanus presents epidemic
      behavior similar to that observed in the developed countries, where the elderly
      represent the main risk group to contract and die from the disease.

PMID- 10967597
TI  - [Prevalence of Cryptosporidium parvum among children of less than 5 years of age
      in the urban zone of Campo Grande, Mato Grosso do Sul State, Brazil, 1996].
AB  - The purpose of this study was to establish the prevalence of Cryptosporidium
      parvum among infants of less than 5 years of age, resident in the urban area of
      Campo Grande, Mato Grosso do Sul State, Brazil, 1996/97, through parasitological
      examinations and epidemiological analysis of the diagnosed cases. It was a
      transverse study with domiciliary inquiry and we evaluated 1051 fecal samples
      processed by the Blagg method, and a modified Ziehl-Neelsen staining was used for
      research of oocysts of C. parvum. We can concluded that the prevalence of C.
      parvum (1.1%) was not statistically significant; 58.3% of the children with
      positive diagnosis presented diarrhea, suggesting an association between this
      sign and the presence of the parasites; C. parvum was more frequent among
      children aged between 25 to 36 months (50%), but this was not statistically
      significant; sex did not have a differential role in relation to the
      cryptosporidiosis; out of the 12 children with cryptosporidiosis, 10 had contact
      with domestic animals (dogs and or cats).

PMID- 10967598
TI  - [Problems with gram-positive bacteria: resistance in staphylococci, enterococci,
      and pneumococci to antimicrobial drugs].
AB  - The resistance in staphylococci, enterococci, and pneumococci is reviewed. The
      author also recalls the first cases, and presents an overview of the distribution
      of cases in the world, the genetic and molecular mechanisms of resistance, the
      importance in Brazil and therapeutic alternatives. The factors that contribute to
      the dissemination of these problem bacteria and the measures for their control
      are emphasized.

PMID- 10967599
TI  - [Critical analysis of the estimated number of Schistosomiasis mansoni carriers in
      Brazil].
AB  - The number of carriers of Schistosoma mansoni infection in Brazil was estimated
      based on the results of parasitological examinations of feces carried out by the
      Fundacao Nacional de Saude (FNS - National Health Foundation) in 1996 and 1997,
      as well as population data from 18 states collected by the Instituto Brasileiro
      de Geografia e Estatistica (IBGE - Brazilian Institute of Geography and
      Statistics). This information allowed the number of carriers of schistosomiasis
      mansoni to be estimated at 7.1 million in 1996 and 6. 3 million in 1997. These
      figures may not reflect the true situation since the population sample used was
      not originally selected for this purpose. The absence of precise data indicates
      the need for an adequate national survey of the prevalence of schistosomiasis,
      which continues to be an important endemic parasitic disease, justifying greater
      efforts for its control in Brazil.

PMID- 10967600
TI  - Intestinal paracoccidioidomycosis simulating colon cancer.
AB  - We report a case of intestinal involvement of Paracoccidioidomycosis, in a
      patient considered to have colonic cancer. The diagnosis of this mycosis should
      be considered when an abdominal mass associated with intra-lesional
      calcifications on X-ray is observed. CT scans increase the findings.

PMID- 10967601
TI  - [Cat-scratch disease caused by Bartonella quintana in an infant: an unusual
      presentation].
AB  - This case study reports a typical clinical course of cat-scratch disease (CSD) in
      an infant without epidemiological data and presenting bilateral submandibular
      lymphadenopathy. The authors describe clinical course, ultrasound images,
      diagnosis and prognosis. Polymerase chain reaction (PCR) detected and identified
      B. quintana in lymph node samples. B. henselae currently thought to be the
      causative agent of CSD was not detected. The PCR assays for B. quintana and B.
      henselae should be available for the investigation of lymphadenopathy, even if
      the infant has not had either cat or dog contact.

PMID- 10967602
TI  - [Prevalence of microbiota in the digestive tract of wild females of Lutzomyia
      longipalpis Lutz & Neiva, 1912) (Diptera: Psychodidae)].
AB  - We dissected the digestive tract of 245 females in pools of 35 flies forming 7
      groups. These flies were Lutzomyia longipalpis originating from Lapinha Cave,
      Lagoa Santa, Minas Gerais. Out of the 8 species of bacteria isolated there was a
      predominancy of Gram negative bacterias (GNB) in the group of non-fermenters of
      sugar belonging to the following species: Acinetobacter lwoffii, Stenotrophomonas
      maltophilia, Pseudomonas putida and Flavimonas orizihabitans. The group of GNB
      fermenters were: Enterobacter cloacae and Klebsiella ozaenae. In the Gram
      positive group we isolated the genera Bacillus thuringiensis and Staphylococcus
      spp.

PMID- 10967603
TI  - How much undernutrition is there in hospitals?

PMID- 10967604
TI  - Interactions between vitamins C and E in human subjects.
AB  - Despite convincing in vitro evidence, a vitamin C-E interaction has not been
      confirmed in vivo. This study was designed to examine the effects of
      supplementation with either vitamin C or E on their respective plasma
      concentrations, other antioxidants, lipids and some haemostatic variables.
      Fasting blood was collected before and after intervention from thirty healthy
      adults in a double-blinded crossover study. Baselines for measured variables were
      established after 2 weeks of placebo supplementation, followed by daily
      supplementation with 73.5 mg RRR-alpha-tocopherol acetate or 500 mg ascorbic
      acid, and placebo, for 6 weeks. A 2 month washout preceded supplement crossover.
      Mean values showed that plasma lipid standardised alpha-tocopherol increased with
      ascorbic acid supplementation: from 4.09 (sem 0.51) to 4.53 (sem 0.66)
      micromol/mmol total cholesterol plus triacylglycerol (P < 0.05), and plasma
      ascorbic acid increased from 62.8 (sem 14.9) to 101.3 (sem 22. 2) micromol/l (P <
      0.005). Supplementation with (RRR)-alpha-tocopherol acetate increased plasma
      alpha-tocopherol from 26.8 (sem 3.9) to 32.2 (sem 3.8) micromol/l (P < 0.05), and
      lipid-standardised alpha-tocopherol from 4.12 (sem 0.48) to 5.38 (sem 0.52)
      micromol/mmol (P < 0.001). Mean plasma ascorbic acid also increased with vitamin
      E supplementation, from 64.4 (sem 13.3) to 76. 4 (sem 18.4) micromol/l (P <
      0.05). Plasma ferric reducing (antioxidant) power and glutathione peroxidase (U/g
      haemoglobin) increased in both groups, while urate, total cholesterol and
      triacylglycerol levels decreased (P < 0.05 throughout). Results are supportive of
      an in vivo interaction between vitamins C and E.

PMID- 10967605
TI  - Comparison of recoveries in breath carbon dioxide of H13CO-3 and H14CO-3
      administered simultaneously by single 6 h constant unprimed intravenous infusion.
AB  - The aim of this study was to assess the bioequivalence of H13CO-3 and H14CO-3, by
      administering both labels simultaneously by single infusion and comparing their
      recovery in breath CO2 and urinary urea. Six healthy male subjects (age range 24
      41 years; weight 76.7 (sd, 18.6) kg; height 1.79 (sd 0.05) m) were infused with
      unprimed solutions of HCO3- (110.0 mmol/kg) labelled with 13C (0.76 mmol 13C/h)
      and 14C (48 Bq/h) at a constant rate for 6 h, in a whole-body calorimeter (1400
      litres) for measurement of CO2 production. Samples of breath were collected
      hourly in a Douglas bag and all urine was collected into two batches (0-4 h and 4
      6 h) for estimating recovery of infused label by measurement of enrichment or
      specific activity. Recovery in breath CO2 of both labels increased from about 25
      % for the first hour to 88 % and above for hours 3-4 onwards. Mean recovery of
      13C in breath CO2 was slightly higher than that of 14C for all periods (mean
      difference always less than 1 % of infused label) but was significant only for
      the first 3 h (P < 0.05). Recovery of 14C in urea was significantly higher (P <
      0.01) than 13C, but was confounded by substantial variability and uncertainties
      concerning 13CO2 background enrichments. These results suggest that there is no
      compelling need to alter factors currently used for recovery of 14C in breath
      when using 13C instead, and vice versa.

PMID- 10967606
TI  - The effects of breed and level of nutrition on whole-body and muscle protein
      metabolism in pure-bred Aberdeen angus and Charolais beef steers.
AB  - Eighteen pure-bred steers (live weight 350 kg) from each of two breeds, Aberdeen
      Angus (AA) and Charolais (CH), were split into three equal groups (six animals
      each) and offered three planes of nutrition during a 20-week period. The same
      ration formulation was offered to all animals with amounts adjusted at 3-week
      intervals to give predicted average weight gains of either 1.0 kg/d (M/M group)
      or 1.4 kg/d (H/H group). The remaining group (M/H) were offered the same amount
      of ration as the M/M group until 10 weeks before slaughter when the ration was
      increased to H. Data on animal performance, carcass characteristics and fibre
      type composition in skeletal muscle are presented elsewhere (Maltin et al. 2000;
      Sinclair et al. 2000). On three occasions (17, 10 and 2 weeks before slaughter)
      the animals were transferred to metabolism stalls for 1 week, during which total
      urine collection for quantification of Ntau-methylhistidine (Ntau-MeH)
      elimination was performed for 4 d. On the last day, animals were infused for 11 h
      with [2H5]phenylalanine with frequent blood sampling (to allow determination of
      whole-body phenylalanine flux) followed by biopsies from m. longissimus lumborum
      and m. vastus lateralis to determine the fractional synthesis rate of mixed
      muscle protein. For both breeds, the absolute amount of Ntau-MeH eliminated
      increased with animal age or weight (P < 0.001) and was significantly greater for
      CH steers, at all intake comparisons, than for AA (P < 0.001). Estimates of
      fractional muscle breakdown rate (FBR; calculated from Ntau-MeH elimination and
      based on skeletal muscle as a fixed fraction of live weight) showed an age (or
      weight) decline for M/M and H/H groups of both breeds (P < 0.001). FBR was
      greater for the H/H group (P = 0.044). The M/H group also showed a lower FBR for
      the first two measurement periods (both at M intake) but increased when intake
      was raised to H. When allowance was made for differences in lean content
      (calculated from fat scores and eye muscle area in carcasses at the end of period
      3), there were significant differences in muscle FBR with intake (P = 0.012) but
      not between breed. Whole-body protein flux (WBPF; g/d) based on plasma
      phenylalanine kinetics increased with age or weight (P < 0.001) and was similar
      between breeds. The WBPF was lower for M/M compared with H/H (P < 0.001) based on
      either total or per kg live weight0.75. Muscle protein fractional synthesis rate
      (FSR) declined with age for both breeds and tended to be higher at H/H compared
      with M intakes (intake x period effects, P < 0.05). Changing intake from M to H
      caused a significant increase (P < 0.001) in FSR. The FSR values for AA were
      significantly greater than for CH at comparable ages (P = 0. 044). Although FSR
      and FBR responded to nutrition, these changes in protein metabolism were not
      reflected in differences in meat eating quality (Sinclair et al. 2000).

PMID- 10967607
TI  - Raised saturated-fat intake worsens vascular function in virgin and pregnant
      offspring of streptozotocin-diabetic rats.
AB  - Adult offspring of severely diabetic pregnant rats are insulin resistant and
      display cardiovascular dysfunction. When pregnant they develop mild
      hyperglycaemia. Diets high in saturated fat have been implicated in the
      development of cardiovascular disease and vascular dysfunction. In the present
      study we have determined vascular function in small mesenteric arteries from
      offspring of normal (OC) and diabetic (OD) rats fed standard chow and offspring
      of diabetic rats fed a diet high in saturated fats (OD-HF) from weaning to
      adulthood, and throughout their subsequent pregnancies. OD rats displayed an
      increased sensitivity to noradrenaline (P < 0.05) and impaired sensitivity to the
      endothelium-dependent vasodilator, acetylcholine. The component of acetylcholine
      induced relaxation attributable to endothelium-derived hyperpolarizing factor was
      reduced in OD-HF rats. Pregnant OD rats also demonstrated impaired maximum
      relaxation to acetylcholine (pregnant OD rats v. pregnant OC rats P < 0.05). In
      pregnant OD-HF rats noradrenaline sensitivity was enhanced and endothelium
      dependent relaxation further reduced (pregnant OD-HF rats v. pregnant OC rats P <
      0.001). The isoprostane, 8-epi-prostaglandin F2alpha, a marker of oxidative
      stress, was increased in pregnant OD rats (pregnant OD rats v. pregnant OC rats P

PMID- 10967608
TI  - Enzyme supplementation of dry and wet wheat-based feeds for broiler chickens:
      performance and gut responses.
AB  - To test whether the improvements in digestive efficiency due to either wetting of
      the food or inclusion of enzymes are accompanied by the same changes in gut
      function, foods with a high content of wheat were fed to broiler chicks from 1-42
      d old. Twenty-four birds were caged individually while a further sixty-four were
      in group pens in experiments of 2 x 2 factorial design with two levels of enzyme
      (0 or 1 g/kg, designed for wheat) and two levels of water addition (0 and 1300
      g/kg). Food intake and live-weight gain were significantly increased by wet
      feeding (from 89.3 to 153.4 g/d and from 39.7 to 65.4 g/d respectively), the
      differences increasing with age, while the enzyme had no significant effect
      (120.5 and 122.2 g/d and 51.9 and 53.1g/week respectively). The viscosity of
      digesta was greatly reduced both by wetting (from 4.40 to 2.64 kPa. s) and enzyme
      (from 4.47 to 2.57 kPa. s) but there was a significant interaction with age in
      which the viscosity was low throughout in the wet only, enzyme only and wet +
      enzyme treatments but declined with age from a very high level in the dry, no
      enzyme treatment (11.5 kPa. s at 14 d). While wetting increased weight and length
      of digestive tract and thickness of some parts of the gut, enzyme had no
      significant effect, tending to reduce gut wall thickness. Crypt cell
      proliferation rate (CCPR) was significantly reduced by wet feeding (from 39.4 to
      28.7 cells/crypt per 2 h) and by enzyme supplementation (from 38.9 to 29.2
      cells/crypt per 2 h). Therefore, while both wetting and enzyme addition to the
      food reduced digesta viscosity and CCPR to a similar extent, the former had
      marked stimulatory effects on food intake and weight gain while the latter had
      little effect. The mode of action of wet feeding is therefore deduced to be not
      primarily through its effects on viscosity and CCPR.

PMID- 10967609
TI  - Effects of milk diets containing beef tallow or coconut oil on the fatty acid
      metabolism of liver slices from preruminant calves.
AB  - Coconut oil (CO) induces a triacylglycerol infiltration in the hepatocytes of
      preruminant calves when given as the sole source of fat in the milk diet over a
      long-term period. Metabolic pathways potentially involved in this hepatic
      triacylglycerol accumulation were studied by in vitro methods on liver slices
      from preruminant Holstein x Friesian male calves fed a conventional milk diet
      containing CO (n 5) or beef tallow (BT, n 5) for 19 d. Liver slices were
      incubated for 12 h in the presence of 0.8 mm-[14C]oleate or -[14C]laurate added
      to the medium. Fatty acid oxidation was determined by measuring the production of
      CO2 (total oxidation) and acid-soluble products (partial oxidation). Production
      of CO2 was 1. 7-3.6-fold lower (P 0.0490) and production of acid-soluble products
      tended to be lower (P = 0.0625) in liver slices of CO- than BT-fed calves. Fatty
      acid esterification as neutral lipids was 2.6- to 3. 1-fold higher (P = 0.0088)
      in liver slices prepared from calves fed the CO diet compared with calves fed the
      BT diet. By contrast with what occurs in the liver of rats fed CO, the increase
      in neutral lipid production did not stimulate VLDL secretion by the hepatocytes
      of calves fed with CO, leading to a triacylglycerol accumulation in the cytosol.
      It could be explained by the reduction of fatty acid oxidation favouring
      esterification in the form of triacylglycerols, in association with a limited
      availability of triacylglycerols and/or apolipoprotein B for VLDL packaging and
      subsequent secretion.

PMID- 10967610
TI  - Resting energy expenditure, activity energy expenditure and total energy
      expenditure at age 91-96 years.
AB  - There is a limited knowledge concerning energy requirements of the elderly,
      especially the oldest old (> 80 years). Energy requirements should be estimated
      from measurements of energy expenditure. For this purpose twenty-one free-living
      individuals (eight males, thirteen females) aged 91-96 years living in Goteborg,
      Sweden were studied. Total body water (TBW) measured by the doubly-labelled-water
      (DLW) technique was 29.5 (sd 5.4) kg in females and 35.6 (sd 4.3) kg in males.
      TBW measured using bioelectric impedance (BIA) was 31.6 (sd 6.4) kg in females
      and 42.0 (sd 7.4) kg in males. The mean difference between TBW measured by BIA
      and that measured by DLW was 3.54 (sd 3.6) kg (P = 0.0002). Resting metabolic
      rate (RMR) was measured using a ventilated-hood system and averaged 5.36 (sd
      0.71) MJ/d in females (n 12) and 6.09 (sd 0.91) MJ/d in males (n 8). Difference
      between measured RMR and predicted BMR (n 20) was 0.015 (sd 0.86) MJ/d (NS).
      Total energy expenditure (TEE) measured by DLW averaged 6.3 (sd 0.81) MJ/d in
      females and 8.1 (sd 0.73) MJ/d in males. Activity energy expenditure (TEE - RMR),
      thus including diet-induced thermogenesis (DIT), averaged 0.95 (sd 0.95) MJ/d in
      females (n 12) and 2.02 (sd 1.13) MJ/d in males. Physical activity level
      (TEE/BMR) averaged 1.19 (sd 0. 19) in females and 1.36 (sd 0.21) (P = 0.08) in
      males. If DIT is assumed to be 10 % of the TEE, energy spent on physical activity
      will be very low in this population.

PMID- 10967611
TI  - Apparent low frequency of undernutrition in Dublin hospital in-patients: should
      we review the anthropometric thresholds for clinical practice?
AB  - Protein-energy undernutrition, or the possibility of its development, has been
      documented to occur frequently in patients on admission to hospital.
      Deterioration in nutritional status is known to occur in hospital. In a
      prospective study of 594 sequential hospital admissions, we aimed to assess the
      prevalence of undernutrition among patients on admission to two acute teaching
      hospitals in Dublin, Republic of Ireland using the widely-accepted anthropometric
      criteria applied in a large study from Dundee, Scotland, UK (McWhirter &
      Pennington, 1994) and to determine changes in nutritional status in hospital. The
      mean prevalence of undernutrition (11 %) was considerably lower than was reported
      from Dundee (40 %). Unintentional weight loss before admission and functional
      impairment on admission occurred to a similar extent in both centres. Weight loss
      in hospital occurred in the same proportion of patients, but less frequently
      among those undernourished on admission to hospital, in Dublin compared with
      Dundee. The patients found to be undernourished on admission in this study had a
      mortality rate in hospital (6.5 %) over three times that of the adequately
      nourished group (2 %). The magnitude of the difference in prevalence of
      undernutrition between the two centres cannot be explained by ethnicity, case-mix
      or age distribution. With the secular increase in BMI in the population, the
      thresholds for classifying patients as undernourished or at risk of nutritional
      deterioration may need to be reviewed. For clinical use, recent weight loss and
      functional status may be more appropriate variables to use in the evaluation of
      nutritional status on admission to hospital.

PMID- 10967612
TI  - Is advice for breakfast consumption justified? Results from a short-term dietary
      and metabolic experiment in young healthy men.
AB  - Short-term (2 weeks) effects of the consumption of a high-energy (2920 kJ (700
      kcal)) or low-energy (418 kJ (100 kcal)) breakfast on dietary patterns, blood
      variables and energy expenditure (indirect calorimetry) were compared in ten free
      living healthy young men in a crossover study. During the high-energy breakfast,
      total energy intake was increased, the intake of protein and lipids was unchanged
      but the intake of carbohydrates was increased. Thus, 48 (sd 4)% of energy came
      from carbohydrates in the high-energy breakfast compared with 42 (sd 5)% in the
      low-energy breakfast. Excluding breakfast, the macronutrient composition of the
      diet remained identical in the two situations. After the high-energy breakfast,
      fasting serum triacylglycerol concentration was higher and HDL-cholesterol
      concentration was lower than after the low-energy breakfast. A high glycaemic
      response was observed in the morning after the high-energy breakfast period,
      while there was a peak of free fatty acids after the low-energy breakfast. The
      high-energy breakfast induced a strong inhibition of fat oxidation throughout the
      day. Although long-term adaptation to a high-energy breakfast cannot be excluded,
      the high-energy breakfast in this study did not appear to be favourable to
      health. Our results do not support the current advice to consume more energy at
      breakfast.

PMID- 10967613
TI  - Efficacy of oral iodised oil is associated with anthropometric status in severely
      iodine-deficient schoolchildren in rural Malawi.
AB  - The effect of anthropometric status on the efficacy of an oral supplement of
      iodised oil (1 ml Lipiodol Ultrafluide, 490 mg I; Laboratoire Guerbet, Aulnay
      sous-Bois, France) was examined in 8-10-year-old schoolchildren (n 197) of
      Ntcheu, a severely I-deficient district of Malawi. The study was a controlled
      trial using the I concentration of casual urine samples to monitor the I status.
      The median urinary I concentration increased from 0.15 micromol/l at baseline
      (51.3 % of children < 0.16 micromol/l, 89.7 % < 0.40 micromol/l, 95.7 % 0.79
      micromol/l) to 0.32 micromol/l at 40 weeks (29.1 % of the children < 0.16
      micromol/l, 71.0 % < 0.40 micromol/l, 96.1 % < 0.79 micromol/l) while the total
      goitre prevalence fell from 63 % to 21 %. Variables of efficacy were estimated
      from a hyperbolic function describing the longitudinal pattern of urinary I
      excretion after the dose. The I retention and I elimination rate, and the periods
      of protection from mild (< 0.79 micromol/l) or moderate (< 0.40 micromol/l) I
      deficiency were obtained for groups of children with differing anthropometric
      status at baseline. Initial height-for-age and mid upper-arm circumference were
      not significantly related to efficacy. However, both the I retention and I
      elimination rate were reduced in children with lower initial weight-for-height.
      Children with lower skinfold thickness at baseline also had reduced I retention,
      which resulted in shorter protection periods from recurrent moderate and mild I
      deficiency. The efficacy of the oral iodised-oil supplement was not related to
      changes in anthropometric status during follow-up, nor was it related to the
      consumption of a food supplement of 1610 kJ immediately before the iodised-oil
      dose. Very low (< 0.16 micromol/l) urinary I concentration, and the presence of
      goitre at baseline were both associated with higher I retention and elimination
      rate. Children with goitre at baseline were found to have a prolonged duration of
      protection against recurrent moderate I deficiency. We conclude that in
      apparently healthy schoolchildren in I-deficient areas, general anthropometric
      status has a little influence on the efficacy of oral iodised oil for correcting
      I deficiency.

PMID- 10967614
TI  - Effects of dietary maritime pine (Pinus pinaster)-seed oil on high-density
      lipoprotein levels and in vitro cholesterol efflux in mice expressing human
      apolipoprotein A-I.
AB  - Maritime pine (Pinus pinaster)-seed oil contains two Delta5 unsaturated
      polymethylene interrupted fatty acids (all cis-5,9, 12-18:3 and all cis-5,11,14
      20:3 acids) one of which resembles eicosapentaenoic acid. The goal of the present
      study was to test whether maritime pine-seed oil consumption affects HDL and
      apolipoprotein (Apo) A-I levels as well as the ability of serum to promote efflux
      of cholesterol from cultured cells. To this end, wild type (WT) non-transgenic
      mice and transgenic mice expressing human ApoA-I (HuA-ITg) were fed on
      isoenergetic diet containing either 200 g maritime pine-seed oil/kg or 200 g
      lard/kg for 2 weeks. WT and HuA-ITg mice fed maritime pine-seed oil had lower
      cholesterol, HDL-cholesterol, LDL-cholesterol and HuA-ITg mice had lower human
      ApoA-I than those fed lard. The differences in cholesterol (P < 0.0001) and HDL
      cholesterol (P < 0.003) levels between mice fed on the two diets were more
      pronounced in the HuA-ITg than in the WT mice. The ability of HuA-ITg serum to
      promote cholesterol efflux in cultured cells was greater (P < 0.008) than that of
      WT animals. However, the maritime pine-seed oil diet was associated with lower (P
      < 0.005) in vitro cholesterol efflux ability than the lard diet in both mice
      genotypes. This suggests a negative effect of the maritime pine-seed oil on
      reverse cholesterol transport. Cholesterol efflux was correlated with serum free
      or esterified cholesterol and phospholipid levels. The slope of the regression
      line was smaller in the HuA-ITg than in the WT mice indicating that
      overexpression of human ApoA-I reduces the negative impact of maritime pine-seed
      oil on cholesterol efflux. In conclusion, maritime pine-seed oil diet lowers HDL
      cholesterol and diminishes in vitro cholesterol efflux. This potentially
      detrimental effect is attenuated by overexpression of human ApoA-I in mice.

PMID- 10967615
TI  - Comparison of children's dietary intake patterns with US dietary guidelines.
AB  - Monitoring dietary intake patterns among children is important in order to
      explore and prevent the onset of adult health problems. The aim of the present
      study was to compare children's dietary intakes with national recommendations and
      to determine whether sex or ethnic differences were evident. This was done using
      a methodology that allows assessment of intake from the major components of the
      Food Guide Pyramid developed by the United States Department of Agriculture
      (USDA: US Department of Agriculture and US Department of Health and Human
      Services (1992)). The sample studied included 110 African-American and Caucasian
      males and females (mean age 9.9 years, BMI 20.1 kg/m2) from Birmingham, AL, USA,
      who were participating in a study investigating the development of obesity.
      Dietary data were based on three 24 h recalls and food group intake was
      determined using the USDA Pyramid Servicing Database. The results indicated that
      a high percentage of subjects failed to meet the recommended number of servings
      from each of the food groups. For example, only 5 % and 9 % met fruit and dietary
      group recommendations respectively. Consumption of foods from the Pyramid 'tip'
      (including discretionary fat and added sugar) contributed almost 50 % of the
      diet. African-Americans were more likely to meet requirements for the meat group,
      with a higher proportion of Caucasians meeting dietary recommendations. Males
      were more likely to meet the vegetable group guidelines although females consumed
      more energy per day from discretionary fat. In conclusion, these results suggest
      that implementation of nutrition education programmes may be important for
      promoting healthy nutrition among American children.

PMID- 10967616
TI  - Composition of bacteria harvested from the liquid and solid fractions of the
      rumen of sheep as influenced by feed intake.
AB  - A study was conducted to determine the effect of the feed intake on the chemical
      composition of bacteria associated with the solid (solid-associated bacteria;
      SAB) and liquid (liquid-associated bacteria; LAB) fractions of rumen digesta, the
      digestive passage kinetics and their relationships. Whole rumen contents were
      sampled after a period of continuous infusion of 15NH3 from four ruminally
      cannulated wethers provided successively with a hay-concentrate diet (2 : 1 w/w
      on a DM basis) at two rates of feed intake: 40 and 80 g DM/kg body weight 0.75.
      SAB had a higher content of organic matter and total lipids (P < 0.001) and a
      similar N content as compared with LAB. The concentration of purines and 15N was
      lower (P = 0.011 and P < 0.001 respectively) in SAB than LAB, whereas the
      opposite was observed for the concentration of amino acids (mg/g DM; P = 0.031).
      An increase in feed intake produced an increase in the N (P = 0.034) and purine
      (P = 0.066) concentrations in bacteria and a decrease (P = 0.033) in their amino
      acid concentrations. Significant increases of rumen outflow rates of liquid and
      particles were also observed with increased feed intake. Rates of rumen outflow
      showed positive and negative linear relationships (P < 0.001) with the purine : N
      ratio and the proportion of amino acid on total N of bacteria respectively. SAB
      contained significantly higher proportions of leucine, isoleucine, lysine and
      phenylalanine and lower proportions of alanine, methionine and valine than LAB.
      The increase in feed intake also induced significant changes in the amino acid
      profile of bacteria, increasing arginine and methionine and decreasing alanine
      and glycine proportions. Results show that the outflow rate of rumen contents is
      a major factor in determining the proportion of nucleic acids and protein in
      rumen bacteria and explains some of the differences observed between LAB and SAB.

PMID- 10967617
TI  - Effect of long-term high-fat feeding on energy balance and liver oxidative
      activity in rats.
AB  - The purpose of this work was to study the effect of early long-term high-fat
      feeding on energy balance and liver oxidative activity. To this end, rats aged
      about 30 d were fed a high-fat or a low-fat diet for 15, 30 or 60 d. Full energy
      balance and energy partitioning measurements were carried out. In addition, we
      measured hepatic mitochondrial and peroxisomal oxidative capacities. Serum levels
      of free triiodothyronine (T3) and leptin were also determined. Rats fed a high
      fat diet showed an increase in metabolizable energy intake as well as in energy
      expenditure, while lipid gain over the whole period was lower than that expected
      due to a decrease in metabolic efficiency. An increase in serum free T3 levels
      was also found in rats fed a high-fat diet after 15 and 30 d. Statistically
      significant correlations between serum leptin levels and body fat mass were found
      after 15, 30 and 60 d of high-fat feeding. Finally, no variation in hepatic
      mitochondrial and peroxisomal fatty acid oxidation capacity was found in rats fed
      a high-fat diet for 15, 30 or 60 d. In conclusion, the results of the present
      study show that young Wistar rats fed a high-fat diet for up to 60 d are able to
      counteract, at least in part, obesity development.

PMID- 10967619
TI  - The mineral nutrition of livestock, 3rd ed

PMID- 10967618
TI  - Dietary fatty acids influence the appearance of tumour necrosis factor-alpha
      receptors on adipocytes following an immune challenge.
AB  - Rats were fed from weaning on chow supplemented with suet or sunflower oil (10 %
      (w/w) each). The appearance of receptors for tumour necrosis factor-alpha on
      perinodal adipocytes from the popliteal depot following a subcutaneous injection
      of bacterial lipopolysaccharide was examined. In rats fed on sunflower oil
      supplemented chow receptors appeared at a time similar to that described in rats
      fed unsupplemented chow, but in rats fed on chow supplemented with suet receptor
      appearance was significantly delayed. The popliteal adipocytes were found to
      contain different proportions of fatty acids as assessed by GLC. These
      preliminary results suggest that the fatty acid component of the diet can, by
      influencing the triacylglycerol-fatty acids within adipocytes, directly alter the
      time course of an early inflammatory immune response.

PMID- 10967620
TI  - Economics of nuclear medicine. Introduction.

PMID- 10967621
TI  - Health technology assessment.
AB  - The developing role and use of diagnostic imaging continue to emerge as disease
      management paradigms are refined and clinical guidelines are employed more often.
      Health technology assessment, HTA (also known as health care technology
      assessment), is fundamentally a form of policy research. By formulating effective
      HTA, the short- and long-term effects of health care technology are studied in a
      systematic and multidisciplinary way. The fundamental aim of all HTA is to assist
      those individuals and organizations who stand to benefit from a new health
      technology (patients), those who will apply the technology (providers), and those
      who will pay for it (payers) to make better decisions about the technology they
      utilize by supplying information that is of a high scientific standard and
      population-based. Effective HTA is especially useful to health care providers,
      payers, professional groups in health care, manufacturers, political decision
      makers and the general public or consumers of health care technology because it
      represents a process through which effective technology can be identified and
      ineffective technology can be understood in the context of its limitations. HTA
      is a multidisciplinary undertaking requiring combined expertise in clinical
      medicine, epidemiology, biostatistics, bioengineering, health economics,
      administration, psychology, sociology, ethics and legal science. Additionally,
      the experiences and opinions of health technology users and consumers of health
      care (especially patient advocacy groups) are needed to form an overall accurate
      understanding of the technology under review.

PMID- 10967622
TI  - The role of cost effectiveness analysis in health care evaluation.
AB  - This paper provides an overview of the key elements of cost effectiveness
      analysis (CEA). CEA is a method for evaluating the relative costs and benefits of
      treatments and procedures. Typically, CEA compares a proposed intervention with
      (at least) one alternative intervention, yielding an incremental cost
      effectiveness ratio. This ratio reflects both the longevity and health status of
      the differing interventions and permits the researcher to more completely compare
      and evaluate the "payoff" of the interventions. This paper discusses different
      perspectives CEA studies might adopt, and reviews the major methods for measuring
      both outcomes and costs.

PMID- 10967623
TI  - Economic evaluation studies in nuclear medicine: a methodological review of the
      literature.
AB  - BACKGROUND: The growing need for evaluation of the utility of new nuclear
      medicine technologies has spawned a few economic studies ranging from preliminary
      indications of cost savings to complete decision analysis models incorporating
      costs and quality of life. The objective of the current study was to evaluate the
      methodological quality of economic analyses of nuclear medicine procedures which
      targeted cost-effectiveness or cost-utility issues published in the medical
      literature during the years 1985-1999. METHODS: A computerized literature search
      was used to identify original investigations from the medical literature which
      included an economic analysis of a nuclear medicine procedure. Each economic
      analysis article was evaluated by two independent reviewers for adherence to ten
      accepted methodological criteria. RESULTS: Of the 29 articles meeting the search
      criteria, only six (21%) conformed to all ten methodological criteria.
      CONCLUSIONS: Published economic analyses of nuclear medicine procedures usually
      do not meet accepted methodological standards and could be significantly improved
      to achieve overall better quality relative to similar analyses in the literature
      from other medical fields. Continued improvement in the number and quality of
      economic studies is critically needed for the future competitiveness of nuclear
      medicine studies.

PMID- 10967624
TI  - Clinical and economic outcomes assessment in nuclear cardiology.
AB  - The future of nuclear medicine procedures, as understood within our current
      economic climate, depends upon its ability to provide relevant clinical
      information at similar or lower comparative costs. With an ever-increasing
      emphasis on cost containment, outcome assessment forms the basis of preserving
      the quality of patient care. Today, outcomes assessment encompasses a wide array
      of subjects including clinical, economic, and humanistic (i.e., quality of life)
      outcomes. For nuclear cardiology, evidence-based medicine would require a
      threshold level of evidence in order to justify the added cost of any test in a
      patient's work-up. This evidence would include large multicenter, observational
      series as well as randomized trial data in sufficiently large and diverse patient
      populations. The new movement in evidence-based medicine is also being applied to
      the introduction of new technologies, in particular when comparative modalities
      exist. In the past 5 years, we have seen a dramatic shift in the quality of
      outcomes data published in nuclear cardiology. This includes the use of
      statistically rigorous risk-adjusted techniques as well as large populations
      (i.e., > 500 patients) representing multiple diverse medical care settings. This
      has been the direct result of the development of multiple outcomes databases that
      have now amassed thousands of patients worth of data. One of the benefits of
      examining outcomes in large patient datasets is the ability to assess individual
      endpoints (e.g., cardiac death) as compared with smaller datasets that often
      assess combined endpoints (e.g., death, myocardial infarction, or unstable
      angina). New technologies for the diagnosis of coronary artery disease have
      contributed to the rising costs of care. In the United States and in Europe,
      costs of care have risen dramatically, consuming an ever-increasing amount of
      available resources. The overuse of diagnostic angiography often leads to
      unnecessary revascularization that does not lead to improvement in outcome. Thus,
      the potential exists that stress SPECT imaging, a highly effective diagnostic
      tool, could effect substantial change in reducing inappropriate use of an
      invasive procedure resulting in cost effective cardiac care. A synthesis of
      current economic evidence in gated SPECT imaging will be presented. In
      conclusion, a current state of the evidence review is presented on the clinical
      and economic data using nuclear cardiology imaging.

PMID- 10967625
TI  - A review of the literature for whole-body FDG PET in the management of patients
      with melanoma.
AB  - BACKGROUND: A review and meta-analysis of the literature on the use of 2
      [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the
      detection of recurrent melanoma was conducted. The goals were to evaluate the
      quality of data reporting and to determine the overall values for the sensitivity
      and specificity of whole body FDG PET and management changes. METHODS: Guidelines
      to evaluate reporting within articles were formulated based on the United States
      medical payer source criteria for assessing studies reporting information on the
      utilization of new medical technology. A meta-analysis was conducted using
      methodology described in the peer reviewed literature. RESULTS: Our MEDLINE PLUS
      search resulted in a universe of 89 total articles. Within these 89, 19 were
      categorized in our targeted content area of which 13 were selected for analysis
      in our targeted subset, with the remaining 70 covering 24 different related
      content areas. Five of 13 (38%) articles in the target subset reported data which
      was adequate for incorporation into modeling objectives based on PET sensitivity
      and specificity values, with 1 of 13 (8%) in the same target subset reporting
      data adequate for modeling based on change-in-management data. Through a meta
      analysis of the 13 target articles we determined, within a 95% confidence level,
      an overall sensitivity of 92% (95% confidence level 88.41%-95.82%) and an overall
      specificity of 90% (95% confidence level 83.26%-96.05%) as calculated by number
      of lesions, for FDG PET detecting recurrent melanoma throughout the whole body.
      Furthermore, limited data available for change-in-management suggests an overall
      FDG PET directed change-in-management value of 22%. CONCLUSIONS: Our review
      suggests that improvements can be made to more effectively report the results of
      these FDG PET studies. The overall values determined through the meta-analysis
      indicate the potential benefits of using FDG PET as a diagnostic/management tool.
      Furthermore, these values should prove useful to assessing the cost effectiveness
      of utilizing FDG PET in the management of recurrent melanoma.

PMID- 10967626
TI  - Decision analysis for the cost effectiveness of sestamibi scintimammography in
      minimizing unnecessary biopsies.
AB  - BACKGROUND: The purpose of this study was to assess if breast cancer screening
      using sestamibi scintimammography (SSMM) in conjunction with mammography (MM) is
      cost effective in avoiding biopsies in healthy patients. METHODS: Quantitative
      decision tree sensitivity analysis was used to compare the conventional MM alone
      strategy (strategy A) with two decision strategies for screening with SSMM; SSMM
      after an indeterminate mammogram (strategy B) or SSMM after both a positive and
      an indeterminate mammogram (strategy C). Cost effectiveness was measured by
      calculating the expected cost per patient and the average life expectancy per
      patient for baseline values as well as over a range of values for all of the
      variables of each strategy. RESULTS: Based on Medicare reimbursement values,
      strategies B and C showed a cost savings of $9 and $20 per patient respectively
      as compared to strategy A. This translates into respective savings of $189 and
      $420 million per year assuming 21 million females undergo screening each year.
      Strategies B and C did however have a loss of mean life expectancy of 0.000178
      and 0.000222 years respectively as compared to strategy A due to interval
      progression of breast cancer in a small number of women. Strategies B and C
      significantly lowered the number of biopsies performed on healthy patients in the
      screening population by 750,063 and 1,557,915 biopsies respectively as compared
      to strategy A. CONCLUSIONS: These results quantitatively verify the potential
      utility of using SSMM in avoiding unnecessary biopsies.

PMID- 10967627
TI  - Utility evaluations for Markov states of lung cancer for PET-based disease
      management.
AB  - BACKGROUND: Utilities for the health outcomes states (Markov states) of non-small
      cell lung carcinoma (NSCLC) should be measured to evaluate management options for
      patients because patients are key participants in the process of care, and their
      assessment of diagnostic and therapeutic value in the options presented to them
      ultimately impacts their net health outcomes. This investigation sought to
      measure utilities for stage-dependent outcomes states of NSCLC. METHODS: Persons
      (n = 23) with suspected NSCLC based on physical findings and computed tomography
      completed a short utilities survey. Utility valuations were obtained according to
      severity of morbidity and varied considerably. Respondents rated these health
      states according to accuracy measures for 18flurodeoxyglucose (18FDG) positron
      emission tomography (PET) imaging and medastinoscopy. RESULTS: The results
      demonstrate that stage-dependent morbidity is an important consideration for
      patients with NSCLC and should be included in any decision analysis regarding the
      evaluation or treatment of NSCLC. Respondents valued the quality of information
      obtained from non-invasive PET and invasive mediastinoscopy comparably. The
      utilities obtained from this investigation are useful in clinical decision-making
      based on Markov processes because they provide an initial estimation of utility
      assessment for 18FDG-based diagnostic evaluation of lung cancer. CONCLUSIONS:
      Consequently, these utilities will be useful in future decision analyses that
      require patient preference in the assignment of the evaluation of decision
      options (branches).

PMID- 10967628
TI  - The willingness to pay for positron emission tomography (PET): evaluation of
      suspected lung cancer using contingent valuation.
AB  - BACKGROUND: In this study, contingent valuation is used to estimate the
      willingness-to-pay (WTP) for positron emission tomography (PET) imaging by
      patients with suspected benign or malignant lung disease. METHODS: Patients (n =
      87) undergoing thoracic computed tomography were surveyed for their WTP for PET
      for the evaluation of lung disease in lieu of further testing. Patients were
      provided background PET information and a two-page self-administered
      questionnaire. The survey queried basic demographic information, perceived risk
      of malignancy, and perceived life expectancy given a diagnosis of malignancy.
      RESULTS: Patients with increased perception of risk were willing to pay more than
      those with lower perceived risk. Patients who were self-payers for their health
      insurance indicated a lower WTP than those who did not pay any out-of-pocket
      insurance premiums. CONCLUSIONS: Individuals are willing to pay additional out-of
      pocket costs for diagnostic imaging to reduce their perception of risk and
      improve their quality of life.

PMID- 10967629
TI  - Clinical trials of cost effectiveness in technology evaluation.
AB  - This article discusses models of efficacy, design of clinical trials and the role
      of mathematical modeling in diagnostic technology evaluation and determination of
      cost-effectiveness. A multi-tiered model of efficacy, which views diagnostic
      imaging as part of a global process of patient management and outcome, has been
      described. The first tier involves imaging efficacy, which must be determined by
      clinical trial. Direct comparison of new and established modalities in a single
      study population has major advantages over randomized controlled trials, which
      are extremely costly and time-consuming and are not appropriate for most
      evaluations of diagnostic modalities. Selection of patients for inclusion in the
      trial, interpretation and verification of results, and determination of a
      reference standard are all possible sources of bias, which need to be identified
      and controlled. Decision analysis modeling can be used to assess diagnostic,
      therapeutic, patient-outcome and cost efficacy, once imaging efficacy has been
      evaluated by clinical trial. Decision analysis is easier and less expensive to
      perform than clinical trials, and results are easily generalizable to other
      settings. Disadvantages arise from the nondescriptive nature of modeling and lack
      of transparency, which make it difficult to evaluate the appropriateness of
      decision tree structures and input data. Modeling is an unavoidable fact of life
      in technology evaluation, since the resources that would be required for full
      evaluation of imaging modalities by clinical trial are not available.

PMID- 10967630
TI  - CT and MRI anatomy of the lumbar spine.
AB  - Lumbosacral spine examinations represent approximately 30% of CT and MRI
      procedures. Aim of this article is to pinpoint the anatomy of lumbosacral spine
      whose knowledge is basic for understanding and interpreting CT and MR images.

PMID- 10967631
TI  - Biomechanics of the spine.
AB  - Instability is one of the pathologic conditions of the spine for which surgical
      treatment is increasingly indicated, even if to-date the definition of
      instability is controversial. Some aspects of the biomechanics of the spine with
      particular reference to the viscoelastic characteristics of its elements and the
      involved loads, are reported. The elasticity of the spine is analyzed with an in
      depth consideration of the concept of stability and instability from the
      biomechanical, clinical and radiographic viewpoint.

PMID- 10967632
TI  - Imaging in degenerative disease of the lumbar spine.
AB  - Degenerative disease involves all spinal components. Conventional radiology and
      digital radiology are the procedures of first choice in order to establish the
      diagnosis. CT and MRI should be considered of second choice, based on precise
      indications. The physiologic aspects of the spine during aging are differentiated
      from the degenerative alterations and relative complications specific of
      arthrosis with modern available imaging procedures.

PMID- 10967633
TI  - Degenerative disease of the lumbosacral spine: disk herniation and stenosis.
AB  - Degeneration of the intervertebral disk complex begins early in life and is a
      consequence of a variety of environmental factors as well as of normal aging.
      Degeneration of bone and soft tissue spinal elements is the most common cause of
      spinal stenosis. The term "degeneration" as commonly applied to the spine covers
      such a wide variety of clinical, radiological and pathological manifestations
      that the word is really only a symbol of our ignorance. Computed tomography and
      myelography have long been used for diagnosing the effects of degenerative
      diseases' of the lumbar spine. Despite the continuous improvement in magnetic
      resonance scanning for this purpose, computed tomography can provide excellent
      screening for disk herniation and spinal stenosis.

PMID- 10967634
TI  - The lumbar spine: imaging in rheumatic disease.
AB  - Seronegative inflammatory spondyloarthropathies include ankylosing spondylitis,
      psoriatic arthritis, Reiter syndrome, juvenile chronic arthritis and colitic
      arthritis. These diseases share some characteristics among which the most
      important is the presence of the histocompatibility antigen HLA B27; moreover the
      frequent overlapping of the various inflammation patterns have accounted for
      their classification in a single group. Diagnostic imaging can differentiate
      among the different forms only if the diagnostic algorithm, based on clinical
      history and laboratory findings is followed, considering the advantages and
      limitations of each method. In this respect, it should be kept in mind that the
      findings relative to the spine and sacroiliac joints allow to establish a
      definitive diagnosis.

PMID- 10967635
TI  - Imaging of sacroiliac joints.
AB  - The early diagnosis of inflammatory and degenerative disease of sacroiliac joints
      is markedly difficult because the clinical pattern is not dissimilar from that of
      diseases involving the lumbar spine and sciatic nerve. Furthermore as in
      inflammations in general, when only structural changes in the synovial membrane
      and cartilage are involved, the findings of conventional radiology are often
      nondiagnostic. CT is now considered the gold standard procedure because in spite
      of its nonnegligible limitations, single lesions in the synovial and ligamentous
      compartments can be distinctively evidenced. MRI, unlike other procedures,
      affords the early nonspecific documentation of intrinsic and/or reactive
      alterations in the subchondral bone, therefore it appears to fill the gap between
      the onset of symptoms and the imaging visualization of sacroiliitis.

PMID- 10967636
TI  - Combined imaging in spondylodiscitis.
AB  - At present, in spite of the advancement in antibiotic therapy no significant
      decrease in the incidence of spinal infections is observed: most likely, this is
      correlated to the increased immigration flows, high risk behaviors (drug
      addiction, alcoholism), immunosuppressive diseases (AIDS, leukemia, lymphoma),
      interventional procedures (iatrogenic causes). Early diagnosis, at times
      difficult and often misunderstood, is facilitated by the use of a correct
      diagnostic algorithm, supported by blood culture, needle aspiration and biopsy.
      Aim of this report was to evaluate the role of the different imaging procedures,
      CT and MRI in particular, for prompt correct therapeutic management.

PMID- 10967637
TI  - Primary bone tumors and pseudotumors of the lumbosacral spine.
AB  - Primary tumors of the spine are relatively infrequent lesions compared with
      metastatic disease, multiple myeloma, and lymphoma which are the more frequent
      neoplasms of the spine and usually manifest with multifocal lesions and thus pose
      little diagnostic dilemma. However, in the presence of a solitary spinal lesion,
      the more uncommon primary tumors of the spine represent an important group of
      entities for diagnostic consideration. The most common benign and malignant
      primary tumors of the spine are enostosis, osteoid osteoma, osteoblastoma, giant
      cell tumor, aneurysmal bone cyst, osteochondroma, chordoma, chondrosarcoma, Ewing
      sarcoma, primitive neuroectodermal tumor, and osteosarcoma. The imaging features
      of these lesions are often characteristic. Radiologists should be aware of the
      appearance of these unusual tumors in order to provide a complete differential
      diagnosis.

PMID- 10967638
TI  - Surgical management of instability of the lumbar spine.
AB  - The surgical management of clinical spinal instability is for many aspects
      controversial since the lack of a precise clinical and instrumental definition of
      instability complicates the implementation of a therapeutic protocol. Both the
      indications and the surgical procedure are not always well defined. Some of the
      most common surgical techniques used in the most frequent causes of instability
      of the lumbar spine: fractures, degenerative disease and spondylolisthesis, are
      described.

PMID- 10967639
TI  - Surgical management of degenerative disease of the lumbar spine.
AB  - With the advances in diagnostic and surgical procedures, for degenerative disease
      of the lumbar spine an aggressive therapeutic approach is more frequently
      indicated. The available surgical procedures are numerous and in continuing
      evolution. Most common surgical procedures used in major degenerative disease of
      the lumbar spine as disk herniation and stenosis are described. Indications,
      results and complications associated to these procedures are also illustrated.

PMID- 10967640
TI  - Postoperative lumbar spine.
AB  - The differentiation between normal sequelae and complications of any surgical
      treatment of the lumbar spine is of the utmost importance. Clinical and
      radiological diagnosis is often difficult. Certainly the introduction of computed
      tomography (CT) and magnetic resonance imaging (MRI) has improved and refined the
      diagnostic possibilities, however not all problems have been resolved. For
      example, the frequent resort in vertebral surgery to metal implants which may
      limit or even prevent the interpretation of CT or MR images, should be kept in
      mind. The main types of surgical procedures involving the lumbar spine are
      briefly reviewed, focusing on CT and MRI appearance of normal sequelae of early
      or late complications and the recurrence of the lesion that necessitated the
      first procedure.

PMID- 10967641
TI  - [Microscopic surgery (Mohs surgery) for skin cancers].

PMID- 10967643
TI  - [Cardiac decompensation after an adenectomy for primary hyperparathyroidism:
      hypocalcemic cardiopathy or cascade effect?].
AB  - A 42 year old woman presented with an auricular tachyarrhythmia as well as a
      congestive cardiac failure ascribed to a viral myocarditis, two months after an
      adenectomy for primary hyperparathyroidism. Serum calcium was low whereas
      parathormone serum was increased suggesting a "hungry bone syndrome". The left
      ventricular dysfunction persisted for a long period even after normalization of
      the serum calcium. The contributory role of hypocalcemia in unexplained or
      refractory heart failure is reviewed. The eventuality of a cascade effect is
      evoked.

PMID- 10967642
TI  - [Closure of an atrial septal defect by a mini-thoracotomy with the help of extra
      corporal circulation].
AB  - AIM OF THE STUDY: "Minimal invasive" surgical closure of an atrial septal defect
      (ASD) is performed under femoro-femoral CPB, the superior vena cava being (IVC)
      drained by a supplementary cannula placed directly through the thoracic opening.
      We present a new technique where both vena cavae are drained by a single 2 stage
      femoral cannula. METHODS: The cannula is introduced through the femoral vein and
      its distal holes are directed into the superior vena cava (SVC) while the
      proximal holes are maintained into the IVC. A centrifugal pump is placed on the
      venous line between the cannula and the venous reservoir in order to improve the
      venous return. Both IVC and SVC are clamped around the cannula to isolate the
      right atrium before opening it and repairing the ASD. RESULTS: We recently
      operated on a 60 years old man using this technique. Passive venous drainage was
      2.6 l/min whereas the perfusion theoretical flow was 5.4 l/min. But adding the
      centrifugal pump increased the flow to 5.4 l/min which ensured an optimal
      perfusion flow. CPB time was 38 minutes and operative time was 140 minutes. There
      were no complications and the patient returned home at day 5 following the
      operation. CONCLUSIONS: Using a single venous cannula for drainage of both vena
      cavae simplifies the technique and therefore contributes to the development of
      "minimally invasive" cardiac surgery.

PMID- 10967644
TI  - [Recent progress in the treatment of rheumatoid polyarthritis].

PMID- 10967645
TI  - [Advance directives, a tool to humanize care].
AB  - The relationship between the patient and a medical care giver is complex
      specially as it implies to the human, juridical and practical points of view. It
      depends on legal and deontological considerations, but also on professional
      habits. Today, we are confronted to a fundamental modification of this
      relationship. Professional guidelines exist, but are rarely applied and rarely
      taught in universities. However, patients are eager to move from a paternalistic
      relationship to a true partnership, more harmonious and more respectful of
      individual values ("value based medicine"). Advance directives give us an
      opportunity to improve our practices and to provide care consistent with the
      needs and wishes of each patient.

PMID- 10967646
TI  - [Community health for aged persons: the activities of the geriatric polyclinic in
      Geneva].
AB  - In addition to its mainly home-based clinical activity, the Geriatric Polyclinic
      has chosen to develop tree programmes with a specific activity. Their common
      objectives being promoting heath and maintaining home-based treatment in the best
      conditions and for as long as possible. This article describes these programmes.

PMID- 10967647
TI  - [Fibromyalgia at the crossroads of rheumatology, psychology and social work].

PMID- 10967648
TI  - [Diffuse Lewy body disease searched out from 114 patients with parkinsonism].
AB  - From 114 patients who had been previously diagnosed as Parkinson's disease, we
      diagnosed six cases as clinically definite "diffuse Lewy body disease (DLBD)"
      according to McKeith's criteria with more strict modifications. Besides a central
      feature, dementia, and core features including parkinsonism, fluctuating
      cognition, and recurrent visual hallucinations, the patients presented some of
      supportive features, that is, repeated falls (4 cases), syncope (5 cases), and
      transient loss of consciousness (all cases). Autopsy, which was performed in 2 of
      the cases, revealed Lewy bodies in various nervous tissues including autonomic
      nervous systems in both cases. 7 cases of probable DLBD and 8 cases of possible
      DLBD, which lacked fluctuating cognition and/or visual hallucinations,
      demonstrated neither of repeated falls, syncope, nor transient loss of
      consciousness. Episodes of these supportive features, which seem to be associated
      with autonomic dysfunctions and/or fluctuating cognition, should be important in
      the differential diagnosis of DLBD.

PMID- 10967649
TI  - [Genetically confirmed spinal muscular atrophy type III with epilepsy, cerebral
      hypoperfusion, and parahippocampal gyrus atrophy].
AB  - We report a 37-year-old female with spinal muscular atrophy (SMA) type III and
      central nervous system (CNS) involvement. She showed gait disturbance at the age
      of 12 years, and difficulty of squatting at the age of 19. On examination at the
      age of 22, she had proximal muscle weakness and atrophy, fasciculation, normal
      sensory system and elevated creatine kinase in the serum. She was diagnosed as
      having SMA type III based on clinical, electrophysiological, and muscle biopsy
      findings. She suffered from subacute necrotizing lymphadenitis at the age of 23
      and from epilepsy at the age of 33. Magnetic resonance imaging showed atrophy of
      parahippocampal gyrus with right side predominance. Single photon emission
      computed tomography (SPECT) using I123-IMP showed decreased accumulations of I123
      IMP in the temporal lobes with left side predominance. Electroencephalogram
      showed theta wave without epileptic burst. SMA gene analysis revealed deletion of
      exon 7 and 8 in survival motor neuron (SMN) gene. A few patients with SMA and CNS
      involvement have been reported without genetic diagnosis. This is the first
      report of genetically confirmed SMA patient with CNS involvement. SMN gene is
      distributed not only in spinal cord but also in brain. The CNS involvement
      detected in this patient may be related to the loss of SMN gene function,
      although coincidental association of SMA and the CNS abnormalities is still
      considered in this atypical case.

PMID- 10967650
TI  - [A case of non-convulsive status epilepticus worsened Wernicke's aphasia
      reversely].
AB  - A 62-year-old right-handed woman had presented progressive speech impediment over
      4 months. She was alert without any convulsions or involuntary movements.
      Neurological examination showed Wernicke's aphasia, constructional apraxia. Her
      magnetic resonance imaging (MRI) showed an old cerebral infarction in the left
      parieto-occipital area, in addition to ischemic changes in the bilateral deep
      white matter. Electroencephalography (EEG) revealed periodic lateralized
      epileptiform discharges (PLEDs) predominant in the posterior left hemisphere. The
      PLEDs as well as the cortical symptoms improved after an administration of anti
      convulsive agents, thus establishing the diagnosis of non-convulsive status
      epilepticus (NSE). It should be emphasized that NSE manifesting as Wernicke's
      aphasia should be distinguished from dementia syndrome because it is a treatable
      disorder.

PMID- 10967651
TI  - [Manifestation of primary biliary cirrhosis and Basedow's disease caused by
      exposure to carbon monoxide in a patient with HTLV-1 associated myelopathy].
AB  - A 55-year-old woman with HTLV-1 associated myelopathy (HAM) was discovered in a
      rentan kotatsu (Japanese foot warmer with a frame and a coverlet by burning
      briquet) with conscious disorder and admitted to an emergency hospital. Her
      conscious disturbance waned the 3rd day after admission with gradual improvement
      of communication and food intake. However, on the 18th day after admission, her
      orientation was poor again and she was unable to take food for herself and keep
      sitting. She was diagnosed as suffering from an interval form of acute carbon
      monoxide (CMO) poisoning and transferred to our hospital for the purpose of
      hyperbaric oxygen therapy on the 20th day after exposure to CMO. In the course of
      treatment she recovered but showed jaundice, pruritus, liver dysfunction and
      elevation of antimitochondrial antibody. She received liver biopsy and was found
      to have primary biliary cirrhosis (PBC). On the 150th day, she manifested
      perspiration and hypertension. The clinical and immunological feature revealed
      her Basedow's disease. The relationship between HAM and PBC due to the autoimmune
      process has been predicted by investigators. The implication of autoimmune
      disease and HLA haplotype is a main focus of attention. Our case supports their
      hypothesis, and suggested that the complication occurred with immunological and
      genetic correlation. Anti-HTLV-1 antibody was positive at a titer of 1:8192
      before exposure to CMO. On transferring to us, it was negative and revealed
      excessive positive at a titer of 1:20,480 on the 80th day. Immunoglobulin
      analysis was normal on admission and increased during hospitalization. It was
      reported that prenatal exposure to relatively mild concentrations of CMO in rats
      reduces splenic macrophage phagocytosis and killing ability as well as macrophage
      respiratory burst. These data suggested that PBC and Basedow's disease were
      manifested by exposure to carbon monoxide.

PMID- 10967652
TI  - [An autopsy case of juvenile neuronal ceroid-lipofuscinosis with dilated
      cardiomyopathy].
AB  - We reported an autopsy case of neuronal ceroid-lipofuscinosis (NCL3) with
      dilatated cardiomyopathy. A 29-year-old male patient first noticed night
      blindness at the age of four years. He was pointed out retinitis pigmentosa at
      the age of six years and developed ataxia, mental retardation, epilepsy and
      myoclonus, thereafter. T1 weighted MRI showed diffuse atrophy of the cerebellum,
      brainstem, and cerebrum, and dilatation of the ventricular system and T2-weighted
      MRI showed mild high signal intensity in the white matter around the trigones of
      the lateral ventricles. Autopsy findings showed an abundant accumulation of
      ceroid-lipofuscin-like lipopigments in most neurons in the central nervous
      system, and curvilinear bodies and lipofuscin like granules were confirmed by
      electron microscopy. The heart muscle showed an increase in the accumulation of
      ceroid-lipofuscin-like lipopigments, severe fibrosis and fatty infiltration in
      the myocardium. The peculiar point of this case is NCL3 with dilated
      cardiomyopathy.

PMID- 10967654
TI  - [Velopharyngeal palsy: a case report].
AB  - Here we present a case of velopharyngeal palsy. An 18-year-old man had hyperemia
      in his left conjunctivum. One or two weeks later he experienced nasal speech and
      difficulty in swallowing. General physical examination was normal. The only
      abnormal neurological finding was palato-pharyngeal paralysis on the right side.
      MRI of the head and neck had no abnormalities. Acute and convalescent sera showed
      no rise in viral antibody titer. CSF examination was normal except for the
      increased IgG% and IgG.albumin index. Treatment consisted of glycerol and
      steroid, and his symptom improved within two or three weeks. We think
      immunological mechanism is important because CSF examination showed increased
      IgG% and IgG.albumin index in our case. Acquired and isolated velopharyngeal
      palsy is uncommon. Only 26 cases have been reported so far. This is the first
      case in Japan. The disease has some characteristics. This occurs in childhood and
      adolescence. Onset is sudden, consisting in rhinolalia and dysphagia. On
      examination there is asymmetry of the pharynx and deviation of the uvula
      contralateral to the affected side. There is no other neurological abnormalities.
      Complete spontaneous recovery is usual. In some cases viral infection is the
      cause, but in most cases the cause is unknown. In contrast, the disease with both
      acquired velopharyngeal palsy and vocal cord palsy is relatively common. This
      occurs in the middle aged or elderly people. In addition to dysphagia and hoarse
      voice, this disease often accompanies neurological abnormalities such as other
      cranial nerve palsy and meningitis, fever, and pain in the pharyngeal region. In
      most cases viral infection is the cause.

PMID- 10967653
TI  - [A family with heat-sensitive myotonia alternating with hypokalemic periodic
      paralysis].
AB  - We report a 34-year-old man with evident family history of paralysis and
      myotonia. He has noticed episodic morning paralysis alternating with muscle
      myotonia since the age of 10 years. When an episode of paralysis occurred, his
      serum potassium level decreased to 2.3 mEq/L and tended to increase to about 4.0
      mEq/L when he complained myotonia. This case is obviously different from several
      already-known diseases, as it is perhaps the first case thermo-sensitive disorder
      of muscle activity in that the myotonia is induced by warm environment but
      paralysis occurs in the setting of cold ambient temperature and hypokalemia.
      Therefore, we are underway to perform molecular genetic analysis of ion channels
      since paramyotonia/hyperkalemic periodic paralysis is known to be associated with
      Na(+)-channel missense mutations, while hypokalemic periodic paralysis is with
      Ca(++)-channel. Addendum: After submission of the manuscript, we identified a
      novel mutation in Na+ channel alpha subunit. The detail of molecular aspect will
      be reported elsewhere.

PMID- 10967655
TI  - [A case of amoxapine-induced tardive dystonia successfully treated with a low
      dose anti-cholinergic agent].
AB  - We report a 63-year-old man who presented with amoxapine-induced tardive
      dystonia. At 49 years of age, he developed depression and was administrated 50 mg
      amoxapine, 4 mg cloxazoram and 3 mg biperiden per day. The daily dose of
      amoxapine was gradually increased up to 150 mg at 58 years of age. At 61 years of
      age and after having been taking amoxapine for twelve years, he noticed a
      rotating left arm and muscle pain in his left shoulder and arm while walking. At
      62 years of age, he stopped taking these three drugs. However, the dystonic
      movements and pain both continued to get worse. Neurological findings revealed no
      abnormality except for a dystonic posture and movements in the neck and bilateral
      arms while sitting, standing and walking. Positron emission tomography with C-11
      raclopride revealed a mild decrease in the dopamine D 2 receptor numbers in the
      bilateral striatum. However, two dopamine agonists, pergolide and bromocriptine,
      worsened his dystonia. In contrast, the daily administration of 2 mg of
      trihexyphenidyl, an anti-cholinergic agent, markedly ameliorated the dystonia
      symptoms. As a result, the long-term co-administration of biperiden, an anti
      cholinergic agent, may mask the toxicity of amoxapine, which may induce tardive
      dystonia.

PMID- 10967656
TI  - [An autopsy case of corticobasal degeneration without prominent cortical
      pathology--an imitator of progressive supranuclear palsy].
AB  - We describe an autopsy case of parkinsonism with bradykinesia, muscle rigidity,
      and dementia as major symptoms. The patient had developed bradykinesia at the age
      of 62, and then muscle rigidity, a parkinsonian posture, bradylalia, and dementia
      gradually appeared. Neurological examination revealed rigidity in the neck and
      limbs, with motion and speech being generally slow. He lacked involuntary
      movements including alien hand, tremor, chorea, and dystonia. Vertical gaze
      palsy, both upward and downward was noted, but other cranial nerves were intact.
      He was diagnosed as suffering from PSP clinically based on vertical gaze palsy,
      bradykinesia, instability on standing and gait, and dementia. Levodopa was only
      transiently effective. Within three years he became bed-ridden and in a state of
      akinetic mutism. At age 65 he died from pneumonia. Neuropathology revealed severe
      neuronal degeneration and gliosis in the substantia nigra. Because atrophy of the
      tegmentum of brainstem, dentate nuclei, inferior olivary nuclei was very mild and
      Alzheimer neurofibrillary tangles in the brainstem were relatively few, PSP was
      ruled out. Cortical neuronal degeneration was not apparent, but in the deep layer
      of cingulate gyrus, frontal lobe, and insula, there were several ballooned
      neurons. Gallyas-Braak silver staining showed no tuft-shaped astrocytes, specific
      for PSP, but it disclosed astrocytic plaques in the basal ganglia and the
      cerebral cortex. At present, astrocytic plaques are recognized as a hallmark of
      corticobasal degeneration (CBD), along with ballooned neurons in the cerebral
      cortex. The present case thus illustrates that CBD has a wide spectrum and may
      include cases in which degeneration of cerebral cortex is very mild.

PMID- 10967657
TI  - [A case of chorea gravidarum with moyamoya disease].
AB  - A 16-year-old girl developed acute left choreic movements during her fourth week
      of pregnancy. She had sometimes had transient ischemic attacks since she was 10
      years old. During the eighth week of pregnancy, a brain MRI showed old ischemic
      lesions deep in the right frontal white matter. Her angiograph revealed a
      complete obstruction of the terminal portion of the right internal carotid artery
      with a developed moyamoya net work. After her abortion, all involuntary movements
      completely subsided. The choreic movements might have been caused not only by
      ischemia, but also by enhanced dopaminergic sensitivity mediated by elevations in
      female sex hormones due to pregnancy.

PMID- 10967658
TI  - [Two cases of thalamic infarction presenting with "thalamic astasia"].
AB  - We report two cases of so-called 'thalamic astasia', associated with thalamic
      infarction. A 76-year-old-man suddenly noted to fall down to the left side
      without severe hemiparesis. An MRI showed an infarction in the superolateral
      portion of the right thalamus. Over eight weeks, his astasia gradually
      disappeared. A 69-year-old-man suddenly noted inability to stand with loss of
      balance. He showed mild hemiparesis, hypesthesia and cerebellar signs on the
      right side. Although right hemiparesis was slight, he was unable to stand by
      himself. An MRI demonstrated an infarction in the ventrolateral to
      ventroposterior portion of the left thalamus. Three weeks later, his symptoms
      except for cerebellar ataxia remarkably disappeared. The overlapped MRI lesions
      of these two cases were localized in the ventrolateral thalamus, such as Vimi
      (nucleus ventrointermedii internus), Vci (nucleus ventrocaudalis internus), Cemc
      (nucleus centralis thalami magnocellularis). These lesions are so-called
      'vestibular thalamic nuclei', in which fibers from vestibulocerebellum are
      terminated. Involvement of the thalamic connectivity explains that two patients
      noted inability to stand. Thus we concluded that these two patients had thalamic
      astasia, described by Masdeu and Gorelick.

PMID- 10967659
TI  - [A family with DRPLA and chronic renal failure].
AB  - We reported a family with dentato-rubro-pallido-luysian atrophy (DRPLA) and
      chronic renal failure. The proband was a 66-year-old woman who developed gait
      disturbance, limb ataxia, pyramidal tract signs, and dementia since age 54. T2
      weighted brain MR images revealed symmetric high-signal lesions in the cerebral
      white matter, in addition to cerebellar, brainstem, and cerebral cortical
      atrophy. She suffered from renal failure and became dialysis-dependent at the age
      of 59, four years after the onset of chronic nephritic syndrome. At the age of
      66, she was admitted to our hospital because of hyperthermia and disturbance of
      consciousness, and died of DIC. Her CAG repeats in the DRPLA gene were 58 and 12.
      An autopsy was performed. The brain weighed 910 g. Histological findings
      confirmed the diagnosis of DRPLA. Her mother died of chronic renal failure. All
      three siblings had cerebellar ataxia, and two siblings had chronic nephritic
      syndrome. Among them, only her younger brother was diagnosed as non-IgA
      glomerulonephritis based on kidney biopsy findings at the age of 48. Though the
      nature of the association between DRPLA and renal dysfunction remains obscure,
      the DRPLA gene abnormality may be correlated with chronic renal failure in this
      family.

PMID- 10967660
TI  - [Hyperlexia in an adult patient with lesions in the left medial frontal lobe].
AB  - A 69-year-old right-handed woman developed a transcortical motor aphasia with
      hyperlexia following resection of a glioma in the left medial frontal lobe.
      Neurological examination revealed grasp reflex in the right hand and
      underutilization of the right upper extremity. An MRI demonstrated lesions in the
      left medial frontal lobe including the supplementary motor area and the anterior
      part of the cingulate gyrus, which extended to the anterior part of the body of
      corpus callosum. Neuropsychologically she was alert and cooperative. She
      demonstrated transcortical motor aphasia. Her verbal output began with echolalia.
      Furthermore hyperlexia was observed in daily activities and during examinations.
      During conversation she suddenly read words written on objects around her which
      were totally irrelevant to the talk. When she was walking in the ward with an
      examiner she read words written on a trash bag that passed by and signboards
      which indicated a name of a room. Her conversation while walking was intermingled
      with reading words, which was irrelevant to the conversation. She also read time
      on analog clocks, which were hung on a wall in a watch store. In a naming task,
      she read words written on objects first and named them upon repeated question
      about their names. When an examiner opened a newspaper in front of her without
      any instructions she began reading until the examiner prohibited it. Then she
      began reading again when an examiner turned the page, although she remembered
      that she should not read it aloud. She showed mild ideomotor apraxia of a left
      hand. Utilization behavior, imitation behavior, hypergraphia, or compulsive use
      of objects was not observed throughout the course. Hyperlexic tendency is a
      prominent feature of this patient's language output. Hyperlexia was often
      reported in children with pervasive developmental disorders including autism.
      There are only a few reports about hyperlexia in adults and some of them were
      related to diffuse brain dysfunction. Hyperlexia of our patient was associated
      with echolalia but not with the other "echo" phenomena, which may be because the
      lesion was unilateral on the left side. Dysfunction of the left supplementary
      motor area could lead to disinhibition of regulatory mechanism of verbal output
      in response to auditory and visual stimuli.

PMID- 10967661
TI  - [Diffusion-weighted magnetic resonance imaging of neuro-Behcet's disease].
AB  - We report 2 patients (35-year-old and 38-year-old men) with neuro-Behcet's
      disease and characterize their diffusion-weighted MRI (DWI) findings of brain. T2
      weighted and fluid-attenuated inversion recovery images obtained during the acute
      phase of neurological manifestations demonstrated multiple hyperintense lesions
      with a characteristic distribution in the brain including brainstem, thalamus,
      basal ganglia, and cerebral hemisphere. Most of these lesions did not exhibit
      increased signal intensity on DWI. This MRI profile, especially the combination
      of isointensity on DWI and hyperintensity on T2-weighted image, of neuro-Behcet's
      disease is similar to that of multiple sclerosis, and different from that of
      acute cerebral infarction and herpes simplex encephalitis.

PMID- 10967662
TI  - [Juvenile cerebral infarction associated with heparin cofactor II abnormality. A
      case report].
AB  - A 15-year-old woman with a history of transient dysarthria two years before,
      suddenly developed weakness of right upper extremity, right facial palsy, and
      dysarthria. She was admitted to our hospital on the third day. She had no
      hypertension, heart murmur and oedema. On neurological examination, she had mild
      right hemiparesis including face muscles and mild dysarthria. The right knee jerk
      was brisk with no Babinski's sign. Ataxia and sensory disturbance were not
      present. T2-weighted MRI showed a hyperintensity at the posterior limb of the
      left internal capsule. Cerebral angiography was unremarkable. Ultracardiography
      and 24-hour electrocardiography were normal. Laboratory data revealed no
      inflammatory findings, liver dysfunction, hyperglycemia and hyperlipidemia.
      Antinuclear and anticardiolipin antibodies were negative. Prothrombin time was
      normal, but activated partial thromboplastin time was slightly prolonged (35.4
      sec, normal 25.2-34.4). Protein C, protein S and antithrombin III were normal.
      Heparin cofactor II (HC II) activity was decreased (44%) with normal HC II
      antigen (79%) and so she was diagnosed as heparin cofactor II deficiency type II
      (heparin cofactor II abnormality). Her father manifesting thromboangitis
      obliterans also had low HC II activity with normal HC II antigen. However, on her
      genetic analysis, we didn't detect any mutations in the coding region of HC II
      gene. Until now she has no recurrence of cerebrovascular attacks. On the basis of
      these results, we suspect that HC II deficiency was a possible risk factor of
      cerebral infarction in this case because she was so young and had no general risk
      factors except for HC II. No stroke associated with HC II deficiency type II has
      been reported up to date. This case is worth considering etiologies of juvenile
      cerebral infarction.

PMID- 10967663
TI  - [A patient with limb-girdle type myasthenia gravis and atopic dermatitis, both of
      which improved after thymectomy].
AB  - We herein report a patient with myasthenia gravis (MG) and atopic dermatitis
      (AD). Heretofore, there have been no reports of patients with MG and AD. Nine
      years ago, a 25-year-old man noted muscle weakness of upper and lower extremities
      on physical labor, and the muscle weakness was gradually exacerbated. Two years
      ago, he noted acute skin eczema with itching on his hands and feet. Neurological
      examination revealed mild left ptosis, facial muscle weakness and proximal muscle
      weakness of upper and lower extremities, but no diplopia, ophthalmoplegia or
      dysphagia. Although anti-nicotinic acetylcholine receptor antibody was negative,
      edrophonium test was positive and 54% waning in the thenar muscles was observed
      on Harvey-Masland test. Thus, he was diagnosed as limb-girdle type MG. IgE level
      in his serum elevated (1,818 U/ml). After thymectomy, the muscle weakness
      markedly improved as well as waning in the thenar muscles (11%). Simultaneously,
      AD markedly improved and serum IgE level was decreased (1,245 U/ml). Thus, MG and
      AD in this case may be derived from some common immunological aberrancy in the
      thymus.

PMID- 10967664
TI  - [A case of Avellis' syndrome with ipsilateral central facial palsy due to a small
      medullary infarction].
AB  - We report a 51-year-old man with mild left central facial palsy and left Avellis'
      syndrome due to a small medullary infarction. On admission, neurological
      examination revealed hoarseness, dysphasia, absent left gag reflex, palsies of
      the left vocal cord and left soft palate, and hypalgesia and thermohypesthesia on
      the right side of the trunk and extremities. In addition, he had a mild left
      central facial palsy. He had no nausea, vomiting, vertigo, hiccups, nystagmus,
      Horner's sign, facial numbness, or paresis or ataxia of the limbs. A T2 weighted
      MRI showed a small, high signal intensity area in the left dorsal region of the
      medulla and this lesion was presumed to involve the nucleus ambiguus and a part
      of the spinothalamic tract. These findings suggest that an aberrant supranuclear
      pathway, looping around the nucleus ambiguus to the facial nucleus exists in our
      patient.

PMID- 10967665
TI  - [Reversible posterior leukoencephalopathy in a patient receiving cyclosporine
      therapy].

PMID- 10967666
TI  - [Radical procedures on the thyroid gland at the turn of the millennium].
AB  - The increasing demands for radical thyroid operations by endocrinologists led
      during the last decade to elaboration of tactics and surgical techniques of
      thyroid operations. Nowadays as radical operation removal of all thyroid tissue
      is considered, and when malignancy is suspected, also removal of the affected
      lymph nodes. While in 1992 the ratio of radical thyroid operations did not exceed
      30%, at present these operations account for more than 90%. Our experience is
      based on results assembled in a group of 4960 patients operated on account of
      thyroid disease with the conclusion, if judged with regard to postoperative
      complications, radical removal of the thyroid gland is nowadays almost equally
      safe as subtotal surgery. Sufficiently radical surgery prevents moreover a
      relapse of the disease. An essential part of treatment of thyroid disease should
      be interdisciplinary collaboration in particular among endocrinologists,
      sonographists and surgeons, not only during preoperative preparation but also
      during the regular postoperative follow up of patients.

PMID- 10967667
TI  - [Bronchial anastomoses in lung transplantation].
AB  - Bronchial anastomosis is as to the number of complications the most risky
      anastomosis of transplanted lungs. The most suitable of hitherto used techniques
      is simple suture with continuous stitches or individual absorbable stitches. The
      authors prefer the latter technique. They performed a total of 34 bronchial
      anastomoses. In none dehiscence or stenosis of the anastomosis was occurred. In
      case of complication of the anastomosis, surgeons often consider the cause of the
      failure to be ischaemia of the border of the tissue at the time of suture of the
      anastomosis, corticoid treatment or a poor nutritional status of the patient. The
      authors cannot confirm the above statements from their own experience, similarly
      as other authors. They are however aware of the fact that their group of
      anastomoses is small.

PMID- 10967668
TI  - [Healing of bronchial anastomoses in lung transplantation: comparison of two
      techniques].
AB  - The authors present a group of patients with transplantations made in 1988 at the
      Department of Cardiac and Thoracic Surgery of the Surgical University Clinic in
      Vienna under the guidance of Prof. W. Klepetko. This department serves also as a
      training place for the centre for transplantations of the lungs in the Faculty
      Hospital Motol. The standard technique of suture of bronchial anastomoses in
      transplantations of the lungs is continuous suture on the pars membranacea and
      individual stitches on the pars cartilaginea of the bronchus. The objective of
      this retrospective study was to compare the results when using the established
      technique with the use of a new technique--suture of the anastomsis by one
      continuous stitch. The technique of one continuous stitch when suturing bronchial
      anastomoses is a safe method which gives similar results as the established
      technique. As it is simpler and saves time, it may be recommended for bronchial
      anastomoses during transplantation of the lungs. While using the mentioned
      techniques only a minimum of complications was recorded.

PMID- 10967669
TI  - [Personal experience with the Lemperle method of reduction mammaplasty].
AB  - The authors describe their experience with Lemperle's method of reduction
      mammoplasty. It is based on the procedure of Wise and Strombeck and involves
      resection of the lower quadrants. We used this operation in seventy patients of
      the age between seventeen and 55 years during last five years. Six of our cases
      (8.6%) were classified as gigantomasty, four of them (5.7%) as hypertrophy with
      asymmetry and sixty patients (85.7%) were classified as hypertrophy with ptosis.
      As to the postoperative complications, two patients (2.8%) developed partial
      necrosis of the areola with dehiscence of the vertical suture and one patient
      (1.4%) partial dehiscence of the vertical suture. The resected tissue volumes
      were between 4,500 g and 400 g. The patients were very pleased with the result of
      the operation.

PMID- 10967670
TI  - [6 years' personal experience with duodenum-sparing procedures in chronic
      pancreatitis].
AB  - The First Surgical Clinic of the First Medical Faculty Charles University and
      General Faculty Hospital Prague made operations of the pancreas ever since 1971.
      In the work sooner or later all approaches to surgical treatment of pancreatitis
      were reflected. The authors present a brief review of results and their own
      experience since 1994 when duodenum sparing operations were introduced.
      Indications for surgical treatment were based on the diagnosis by US, CT and
      ERCP, in exceptional cases MR, after evaluation by a pancreatologist,
      roentgenologist and surgeon. The group of patients with chronic pancreatitis was
      extended by 15 patients from a group operated because of preoperative suspicion
      of a malignant pancreatic tumour not confirmed during and after surgery. In those
      Whipple's operation was performed. The same operation was performed in three
      patients with chronic pancreatitis with serious changes in the area of the head
      of the pancreas. In 111 patients a drainage and duodenum sparing operation was
      performed. Of these in 46x according to Neger, 9x according to Frey, 10x
      modification of these operations, 37x Partington-Rochelle's procedure. The
      authors did not record postoperative complications after the classical Beger
      operation and the hospital stay was on average by five days shorter as compared
      with the classical method of Whipple. When evaluating postoperative complaints
      and problems (pain, malnutrition, physical constitution and social position) the
      authors recorded equally favourable results as after non-complicated
      duodenopancreatectomy. They varied, depending on the patient s co-operation round
      87% while after longitudinal drainage of the duct a satisfactory result was
      recorded in 78% of the operated patients. The authors consider Beger's operation
      logical because of the removal of the main tissue mass of the head of the
      pancreas, responsible for pain, complications caused by fibrosis in the area
      round the bile duct and duodenum, responsible for the deterioration of the
      compartment syndrome in the left half of the gland. Its result is destruction of
      the remainder of exocrine and endocrine tissue. Of 170 operated patients one
      patient with decompensated diabetes died. Based on their own experience the
      authors do not consider repeated re-operations an absolute contraindication of
      Beger's operation when conditions permit. A problem is, in their opinion,
      fibrosis in the vicinity of the pancreas and portal overpressure.

PMID- 10967671
TI  - [Manually-assisted laparoscopic surgery].
AB  - The authors describe and discuss a new method of minimally invasive surgery--hand
      assisted laparoscopic surgery. For the analysis they used recent data from the
      literature and their own experience. The main advantage is greater safety, better
      diagnosis by palpation and better preparation in the abdominal cavity. The main
      disadvantage is the cost of the method.

PMID- 10967672
TI  - [Recurrent acute hemorrhage in the duodenum as a symptom of Bouveret's syndrome].
AB  - The authors demonstrate on the case-history of a 51-year-old patient the rare
      cause of repeated haemorrhage into the digestive tract calling for emergency
      surgery. On operation they found as the cause a solitary biliary concrement which
      penetrated into the duodenum and caused haemorrhage of its wall. The disease was
      described in 1896 by Bouveret as a syndrome of duodenal obturation by a large
      gallstone. In the described case the whole concrement did not yet penetrate into
      the duodenum to cause its obturation but it produced repeated haemorrhage which
      could not be treated by conservative methods.

PMID- 10967673
TI  - [Meckel's diverticulum in a 17-year-old boy as a cause of intermittent chronic
      pain in the umbilical area and the development of sudden abdominal inflammation-
      case report].
AB  - The authors present an account of a large Meckel's diverticulum in a 17-year-old
      boy as the cause of chronic intermittent pain in the umbilical area, rare at this
      age, with development of acute inflammatory abdomen. During an emergency
      operation resection of the diverticulum was performed with 10 cm of the adjacent
      ileum and anastomosis of the ileum end-to-end. The patient recovered after
      surgery per primam intentionem and is free from complaints. The authors draw
      attention to the difficult preoperative diagnosis of this disease as well as to
      possible contemporary diagnostic and therapeutic possibilities.

PMID- 10967674
TI  - [Gene therapy of liver tumors].
AB  - The aim of this review is to describe current possibilities of gene therapy in
      liver tumours. The authors discuss the following methods which were used in
      experimental clinical trials: tumour suppressor genes, suicide gene therapy,
      immunogene therapy and use of oncolytic viruses. The results from these first
      clinical trials were encouraging. However, because of the present limitations,
      such as safe transport and selective expression of genes in the malignant cells,
      gene therapy cannot be used as a definitive treatment for liver tumours.

PMID- 10967675
TI  - [The moist wound healing system in an experiment and clinical practice].
AB  - We compared two types of moisture-retentive dressings (dressings that are capable
      of maintaining a moist environment) in wound healing. The conventional method of
      using an impregnated gauze in combination with a moist wound dressing was
      compared with TenderWet. First, we report results from an in vitro study and an
      animal experiment that included assessment of reepithelization and incidence of
      wound infection. Secondly, we discuss our experience using TenderWet in a
      clinical setting. Two cases of deep dermal burns are described and documented in
      detail. The results of our work suggest that a moist wound environment is more
      effective in facilitating wound healing than conventional methods.

PMID- 10967676
TI  - [Preservation of venous grafts].
AB  - The objective of the work was to find an optimal preservation medium for short
      term preservation of venous grafts which could be subsequently used to line metal
      stents. The external jugular vein of dogs (n = 15) was removed surgically,
      divided into portions and immersed into preservation media. For hypothermic
      preservation (+4 degrees C) solutions of Optisol (Chiron, USA), University of
      Wisconsin (Baxter, USA), Eurocollins (Fresenius, GFR) and saline (Bieffe Medital,
      Italy) were used. For normothermic preservation (+37 degrees C) in an atmosphere
      with 5% CO2 Dulbecc's medium for tissue cultures (Sigma, USA) was used. During
      hypothermic preservation the specimens were kept for 24 hours, 3 and 7 days,
      during normothermic preservation in Dulbecc s medium also for 24 hours, 3 and 7
      days. The specimens were evaluated by light microscopy and raster electron
      microscopy. The results revealed that minimal changes on the endothelia of venous
      grafts occurred during normothermic preservation in Dulbecc's medium where after
      7 days the endothelium did not become detached and the vitality of cells did not
      change. During hypothermic preservation the solution of Wisconsin University
      proved most suitable. By addition of 5% human albumin to this solution it proved
      possible moreover to reduce pyknosis of the endothelial cell nuclei. The
      specimens kept in saline displayed deformities of the nuclei, oedema and loss of
      endothelia incl. incipient oedema of the cellular wall already after 24 hours of
      hypothermic preservation. The authors consider the use of this solution
      unsuitable for preservation.

PMID- 10967677
TI  - [Latent injury of the brachial artery--case report].
AB  - The author presents an account on a subtotal asymptomatic penetrating injury of
      the brachial artery which was treated after a 5-day latency following injury.
      They draw attention to the necessity of careful treatment of minor stab wounds.

PMID- 10967678
TI  - [A rare case of necrotizing fasciitis and subsequent sepsis with multiorgan
      failure caused by Vibrio vulnificus].
AB  - The authors report a rare case of necrotizing fasciitis, sepsis caused by a
      strain of Vibrio vulnificus rare in Czech Republic.

PMID- 10967679
TI  - [Complaints of patients or their relatives regarding surgical complications].
AB  - The authors analyse complaints of patients or their relatives in connection with
      surgical complications in 1987 to 1997 and illustrate them by short case-records.
      During this period, they evaluated 52 complaints and among them 27 fatal. Most
      complaints were from abdominal surgery. Finally, they emphasize the importance of
      high surgical professionality, early discovery of a complications, early,
      sufficient and suitable informing of the patient and his relatives, by the head
      of the department and in severe or fatal complications the management of the
      hospital. They emphasize also the requirement of precise and exhaustive records
      and autopsy.

PMID- 10967680
TI  - [Comments on the article by Dr. V. Marecek:"Trauma department or trauma team?"].

PMID- 10967681
TI  - [Comments on the article by Dr. V. Marecek: "Trauma department or trauma team?"].

PMID- 10967682
TI  - [Comment on the article by Dr. V. Marecek: "Trauma department or trauma team?"].

PMID- 10967683
TI  - [A new paradigm of osteoclast biology: discovery of OCIF and ODF].

PMID- 10967684
TI  - [New aspects of physiological roles of serine/threonine phosphatase 2B,
      calcineurin].

PMID- 10967685
TI  - [Structure and pathogenic functions of trypsin-like cysteine proteinases
      (gingipains) from Porphyromonas gingivalis, a causative bacterium of
      periodontitis].

PMID- 10967686
TI  - [Platelet receptors for collagen].

PMID- 10967687
TI  - [A morphogen gradient made through biosynthesis of bone morphogenetic proteins].

PMID- 10967688
TI  - [WASP-family, a critical signal transducer linking various signals to rapid actin
      polymerization].

PMID- 10967689
TI  - [Transgenic skinny mice overexpressing leptin].

PMID- 10967690
TI  - D. J. du Plessis Lecture. Surgical research--does the patient benefit? Presented
      at the Surgical Research Society of Southern Africa meeting, Bloemfontein, 28-29
      July 1999.

PMID- 10967691
TI  - Primary cricopharyngeal achalasia in infancy--myotomy treatment of choice.
AB  - Dysphagia secondary to primary cricopharyngeal achalasia (PCA) is infrequently
      seen in paediatric patients. Two female children with PCA who had recurrent
      attacks of aspiration pneumonia are presented. A cricopharyngeal myotomy was
      successfully performed in both cases, confirming its efficacy. Investigation and
      management of this rare condition are reviewed.

PMID- 10967692
TI  - Congenital diaphragmatic hernia repair--impact of delayed surgery and epidural
      analgesia.
AB  - This study was undertaken to assess the impact on mortality and the need for
      postoperative ventilation of intra- and postoperative epidural analgesia and
      delayed surgery in neonates with congenital diaphragmatic hernia. The study was a
      retrospective chart review of 35 neonates with congenital diaphragmatic hernia
      treated in Durban between 1988 and 1993. The mortality rate was 30%, with too few
      patients having delayed surgery to demonstrate a benefit from this policy.
      Mortality and the requirement for postoperative ventilation were reduced in the
      epidural group. However, the patients with the worst prognosis all received
      general anaesthesia. The benefit of delaying surgery for congenital diaphragmatic
      hernia repair could not be demonstrated because of small numbers. Epidural
      analgesia appears to be a useful technique to reduce the need for postoperative
      ventilation following repair in lower-risk patients.

PMID- 10967693
TI  - Use of arm veins for lower extremity arterial bypass--results, anatomical
      features and technical considerations.
AB  - Forty lower limb bypasses using arm veins were performed on 37 patients. The
      indications for surgery were limb threat in 50% of cases, graft failure in 33%,
      aneurysms in 10% and claudication in 7%. Saphenous veins were absent because of
      prior use in 73% of cases, and because they were unsuitable in 27%. A single vein
      was used in 48%, 2 veins in 40% and 3 veins in 12% of cases. Seventy-four per
      cent of cases had a single-vessel run-off below the distal anastomosis. Eighty
      two per cent of the distal anastomoses were to infrapopliteal arteries. The
      primary and secondary rates of these 40 bypasses at a mean follow-up of 14 months
      (range 1-40 months) were 74% and 90%, respectively. Limb salvage was 94%. Peri
      operative morbidity and mortality were 23% and 3%, respectively. The anatomical
      and technical aspects of harvesting arm veins are critical to the success of this
      procedure and will be emphasised. We have found arm veins to be a durable source
      of accessible autogenous grafts for lower limb revascularisation in the absence
      of suitable saphenous veins.

PMID- 10967694
TI  - Geophagia--a forgotten diagnosis?

PMID- 10967695
TI  - [Endocrinolgy of estrogens: some recent developments and future applications].
AB  - The interaction of oestrogens with their intra-nuclear receptor is now recognized
      in its tri-dimensional aspects. A new receptor, ER beta, has been cloned and new
      non-genomic oestrogen effects have been reported. Hence, a better understanding
      of physiological mechanisms or of pathophysiological aspects, such as phyto- and
      xeno-oestrogens' influence on the organism, is possible. New compounds, belonging
      to the SERM family, are being explored. Raloxifene is now available for the
      prevention of post-menopausal osteoporosis. Tamoxifen has been associated with a
      beneficial effect for the primary prevention of breast cancer in a high-risk
      population. The understanding of genetic susceptibility could contribute, to
      better define women at risk. A dedicated primary prevention strategy in women
      with a high risk of breast cancer coupled with early detection through
      mammography will continue to improve the prognosis of this hormono-dependent
      cancer.

PMID- 10967696
TI  - [Molecular diversity of calcium channel activities by depolarization].
AB  - Voltage-gated calcium channels are involved in a large variety of cellular
      functions such as excitation-contraction coupling, hormone secretion, firing and
      pacemaker activity, gene activation and proliferation. Cloning of complementary
      DNAs encoding for calcium channel subunits has challenged the study of the
      functional properties of calcium channels and has allowed analysis of the
      molecular basis of calcium channel diversity. Recently, pore-forming subunits of
      T-type calcium channels have been cloned. Recent data describing the genes
      encoding calcium channels, their molecular and pharmacological studies, as well
      as their linkage to human genetic diseases are reviewed in this article.

PMID- 10967697
TI  - Therapeutics teaching: problems in prescribing long-term treatment for chronic
      diseases.

PMID- 10967698
TI  - [The quality of life of hypertensive patients treated with prazosin (sustained
      release) or enalapril: a randomized controlled trial over 24 weeks].
AB  - The importance of the criterion of Quality of Life (QOL) for compliance with
      antihypertensive drugs led us to study the QOL of 51 hypertensives receiving 2.5
      mg of the new formulation of prazosin (sustained release), compared with 49
      subjects treated by a converting enzyme inhibitor (enalapril 10 mg), in a double
      blind randomized trial. QOL, assessed by means of a 22 item self-administered
      questionnaire, improved significantly with prazosin, during the 24 weeks of the
      trial. In the intention to treat analysis, the global score of QOL increased from
      46.3 +/- 8.4 to 51.6 +/- 8.9 (p < 0.0001); the covariance analysis showed that
      the improvement was obtained as early as the 8th week. A similar favourable
      evolution was observed for anxiety, retardation and anhedonia components,
      computed from the same questionnaire. No significant difference in QOL evolution
      was found between prazosin and enalapril. Both treatments proved equivalent in
      respect of efficacy on blood-pressure values, and tolerance, estimated through
      the number of dropouts or side-effects. These results confirm the benefit to QOL
      of hypertensive patients of the new formulation of prazosin.

PMID- 10967699
TI  - Clinical pharmacokinetics during plasma exchange.
AB  - Drug removal during plasma exchange (PE) is a complex phenomenon that is defined
      by the molecule pharmacokinetic characteristics. Plasma-protein binding and the
      volume of distribution (Vd) are two kinetic parameters that strongly affect the
      efficiency of drug removal by PE. The effect of PE on drug kinetics has been
      specifically studied with antivirals, cardiotonic agents, antibiotics,
      corticosteroids, antalgics, anti-epileptic agents and non-steroidal anti
      inflammatory drugs. This effect can be evaluated using different parameters:
      extracorporeal clearance, half-life, amount eliminated, and fraction of the drug
      removed. The estimated fraction eliminated (Fe) from the body by PE is the best
      parameter to evaluate the effectiveness of the exchange procedure; it can account
      for 0.5-30 per cent. Results reported in the literature showed that PE most
      influences drugs with a low Vd, regardless of the extent of protein binding. We
      established that, during PE, there is a linear relationship between Fe and the
      fraction of the drug in extracellular fluids. The fraction eliminated during PE
      is approximately one-seventh of the fraction of the drug in extracellular fluids.
      We propose to use this extracellular fraction as a predictive index: when < 20,
      extraction is low; the amount eliminated becomes consequential only when the
      index > 20. Dosage supplementation may be needed to maintain an adequate drug
      concentration in the body. Practically, for drugs with a low Vd (< 0.3 l/kg), it
      seems necessary to adjust the dosage.

PMID- 10967701
TI  - [Lactic acidosis and metformin implicated: why better information about risk
      factors?].
AB  - In type II diabetes treated with metformin (Glucophage) lactic acidosis is a rare
      adverse reaction, fatal in approximately 50 per cent of cases. Metformin is
      implicated by plasma and intra-erythrocyte levels. An analysis is carried out on
      available information about this risk for healthcare professionals and for
      patients. A comparison is made of approved labelling information on Glucophage
      and its patient leaflets in France and in the USA and an analysis made of the
      differences. In France, Information given to physicians, pharmacists and patients
      on the risk of lactic acidosis where Glucophage is implicated must be improved,
      and on the interest of the metformin plasma level in this case. These are primary
      points because the issue for the few patients concerned may be fatal. Advice on
      self-medication may be introduced. The evolution of information provided on these
      risks depends on the pharmaceutical laboratory, government authorities and
      healthcare professionals.

PMID- 10967700
TI  - [Can we use a Bayesian method to build a pharmacokinetic population in two
      steps?].
AB  - The aim of this study is to evaluate the use of a pharmacokinetic population
      model built by the two-stage method and individual parameters determined by a
      Bayesian estimation instead of nonlinear regression. We performed a retrospective
      analysis on 32 patient files (mean age: 82 years). First, we analysed prediction
      of amikacin serum levels for the Bayesian method (MAP) and nonlinear regression
      (MLS). Second, we compared pharmacokinetic parameter values for each patient with
      MAP and MLS methods for a one- or two-compartment model. For the one-compartment
      model, no difference in prediction performance was found (correlation
      coefficient: rMLS = 0.911, rMAP = 0.903, p > 0.05; precision: pMLS = 134.3, pMAP
      = 147, p > 0.05). A significant difference was observed only for systematic error
      (eMLS = -4.47, eMAP = -3.34, p < 0.05). For a two-compartment model, the Bayesian
      method was better for long-term prediction: 4-8 days (rMLS = 0.877, rMAP = 0.886,
      p > 0.05; eMLS = 5.26, eMAP = 0.04, p < 0.01; pMLS = 441.7, pMAP = 149, p <
      0.05). The comparison of MAP and MLS estimated pharmacokinetic parameter values
      for a one-compartment model showed that the Bayesian method used to built a
      pharmacokinetic population in two stages does not influence pharmacokinetic
      parameter estimation (p > 0.05 for Vd, Kslope, Kel and t1/2). We conclude that we
      can use a Bayesian method to build a pharmacokinetic population in two steps in
      order to perform adaptative control of a drug-dosage regimen.

PMID- 10967702
TI  - [Practical reflections on the diversion of drugs].
AB  - The drugs most diverted for toxicomanic use from their therapeutic indication are
      principally the opioids or related substances, with codeine still high in
      importance, in spite of the wide prescription of substitution treatments. The
      psychotropic drugs, essentially the benzodiazepines and the stimulant
      antidepressants such as amineptine, are also frequently used. The market
      withdrawal of amineptine should diminish its misuse. The abuse of amphetamines
      anorectics and barbiturates seems to be regressing. Nevertheless, substances such
      as nitrous oxide and ketamine are the subject of selective, recent misuse.
      Moreover high-dose buprenorphine misuse, as a concomitant buprenorphine
      benzodiazepine combination and/or an intravenous injection of high doses of
      buprenorphine, can be implicated in severe adverse effects. Twenty-one lethal
      intoxications linked to such drug misuse have already been reported. However, the
      addictive drug potential is not the only explanation for drugs diverted for
      toxicomanic use. It is also associated with a polytoxicomania, a symptom of pre
      existing difficulties, particularly familial, social and environmental in origin.
      Therefore, the therapeutic regime should be adapted to the drug addict's
      personality. We report a few cases of polydrug abusers, treated with methadone in
      a specialist unit. The misuse and the practical therapeutic response, adapted to
      each case, are compared and discussed in respect of the data published in the
      literature.

PMID- 10967703
TI  - [Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral
      sclerosis].
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly fatal degenerative disorder of
      the motoneurones which was without any effective therapy until 1997. Riluzole
      (Rilutek) has been the first patented drug used in its specific treatment. In
      order to evaluate the tolerability profile of this molecule, a Pharmacovigilance
      study was undertaken in the Department of Neurology B at the Montpellier
      University Hospital. A total of 153 patients were studied and all observed side
      effects were listed in the French bank of Pharmacovigilance. Riluzole induced one
      or more adverse effects in 50.3 per cent of patients. The most frequent were
      gastrointestinal disturbances, hepatotoxicity and asthenia. Dermatological,
      haematological, neuropsychiatric and metabolic side-effects were also reported.
      This study shows an acceptable safety profile for riluzole. Due to its mode of
      action, riluzole could potentially be used in the treatment of other
      neurodegenerative diseases involving glutamate excitotoxicity. Subsequently,
      Pharmacovigilance will have to be carried out to establish the proper use of
      riluzole.

PMID- 10967704
TI  - [Strategic analysis and the drug industry].
AB  - During the postwar decades, the quasi-spontaneous growth permitted less rigorous
      management than that of today in terms of the development of enterprises. The
      choice was made in a more or less well-considered way and often by 'feeling'. The
      economic upheaval that followed the oil crises, the acceleration of technological
      discoveries and their practical applications and the speeding up of the
      dissemination of information have imposed a new way of strategic decision making
      on society. This type of approach, used largely in the industrial world, ought to
      be better understood by doctors so that they may appreciate the changes and also
      so that they can eventually use these methodologies in their field of activity.

PMID- 10967705
TI  - [Mental confusion from interaction of a proton-pump inhibitor with
      benzodiazepines: 3 cases].

PMID- 10967706
TI  - [Hypersensitivity syndrome to nevirapine].

PMID- 10967707
TI  - [Intoxication from venlafaxine combined with benzodiazepines, lithium and
      alimemazine].

PMID- 10967709
TI  - [Gene therapy approaches in chronic viral hepatitis].
AB  - The clinical and socioeconomic background of chronic viral hepatitis is
      favourable to new therapeutic approaches based on gene biochemistry. As with all
      gene therapy, the treatment of chronic viral hepatitis using this approach would
      make use of a therapeutic gene and a delivery system adapted to the
      pharmaceutical objectives of targeting, gene expression and kinetics. The various
      vectors under review are not yet sufficiently optimized for selective targeting
      of infected hepatocytes. Moreover, four therapeutic gene processes are currently
      under development: antisense oligonucleotides, ribozymes, dominant negative
      mutants and DNA vaccines. These developments are obviously limited by the lack of
      experimental or animal models representative of the pathophysiology of chronic
      viral hepatitis. The gene therapy for chronic viral hepatitis is nearly ready for
      clinical evaluation but must be weighed against the continuous progress of
      pharmaceutical treatments.

PMID- 10967708
TI  - [Intoxication with amisulpride (Solian): a case with toxicologic documentations].

PMID- 10967710
TI  - [Tolerance and dependence on opioid analgesics: experimental and clinical
      aspects].
AB  - Long-term administration of morphine for chronic non-malignant pain continues to
      be controversial, mainly because of the fear of opioid addiction and abuse. It is
      important to distinguish three phenomena: tolerance of the analgesic and side
      effects of the drug, physical dependence (which is a pure pharmacological event)
      and addiction (defined as a compulsive drug-related behaviour). Animal studies
      suggest that similar mechanisms underlie tolerance and physical dependence. These
      may result from an imbalance between anti- and pro-nociceptive mechanisms. By
      contrast, the occurrence of an addictive behaviour depends on both different
      endogenous mechanisms and environmental factors. Clinical data suggest that the
      use of stable doses of morphine (or other opiates) is common in patients
      suffering from chronic non-malignant pain. However, drug addiction might develop
      in 'at-risk patients' and therefore the decision to start long-term treatment
      with an opiate should be undertaken very cautiously, and ongoing assessment of
      aberrant drug-related behaviours should be undertaken repeatedly.

PMID- 10967712
TI  - Similarities and/or dissimilarities of CYP2D6 polymorphism in three Tunisian
      ethnic groups: Arabs, Berbers, Numides.
AB  - Using the validated probe drug debrisoquine and the 8 h urinary metabolic ratio
      debrisoquine/4 hydroxy-debrisoquine, we have determined the phenotype of the
      debrisoquine CYP2D6 dependent polymorphic metabolism in 464 Arabs, 227 Berbers
      and 215 Numides to elicit similarities or dissimilarities of poor metabolizer
      (PM) prevalence. We found 2.36 per cent of PM in Arabs, 3.08 per cent in Berbers
      and 2.33 per cent in Numides. These figures are similar to those observed in
      Middle East populations, and cannot be considered as different from those
      observed in Caucasians.

PMID- 10967711
TI  - Drug extrapyramidal side-effects or not: is there a dextromethorphan phenotype
      difference?
AB  - A recent hypothesis suggests the possible role of cytochrome P450 2D6 (CYP2D6)
      polymorphism (involved in the metabolism of a large number of drugs), as a
      potential risk factor for the development of extrapyramidal side-effects of
      psychotropic drugs. The CYP2D6 metabolizer phenotype (dextromethorphan test) of
      31 drug treated psychiatric adult patients suffering from extrapyramidal side
      effects (group 1) and of 31 matched patients without drug side effects (group 2)
      were compared. In the first group, 13 poor metabolizer patients (41.9 per cent)
      were found, characterized by a dextromethorphan metabolic ratio > 0.3, and only
      two patients in the second group (6.4 per cent). These data provide some support
      for the notion that in subjects in whom CYP2D6 is probably saturated, the risk of
      drug extrapyramidal side-effects may be increased. In such patients the choice of
      psychotropic drugs 'without' this risk must be preferred.

PMID- 10967713
TI  - Analysis of N-acetyltransferase (NAT2) in three ethnic groups in Tunisia.
AB  - Acetylation status was compared, using caffeine as a probe drug, in the three
      main racial/ethnic groups living in Tunisia: Arabs, Berbers and Numides. The
      frequency of slow acetylators appears identical in these three groups and is
      different from that observed in Caucasians. However, the NAT-2 activity as a
      whole is lower in Tunisians than in Caucasians. These differences might be
      attributable to the various population mixings which occurred in the past, given
      the geographical position of Tunisia. It may be asked whether these differences
      are relevant in term of efficiency and/or frequency of adverse drug reactions
      when medicines whose metabolism is NAT-2 dependent are used. This hypothesis
      deserves to be tested.

PMID- 10967714
TI  - Autoimmune cytopenias associated with malignancies and successfully treated with
      intravenous immune globulins: about two cases.
AB  - The authors report on the cases of two adult male patients presenting with
      autoimmune cytopenias associated with malignancies: a case of autoimmune
      haemolytic anemia occurring after remission of Hodgkin's disease and a case of
      autoimmune neutropenia in the setting of renal carcinoma. High-dose intravenous
      immune globulins (IIG) administered after failure of corticosteroid therapy
      produced a rapid and long-lasting response. These cases illustrate that
      intravenous immunoglobulins may be helpful in refractory cases of autoimmune
      cytopenias. The association of IIG and corticosteroid could be synergistic and
      effective independently of the outcome of the underlying disease. The
      pathophysiogenic mechanisms and literature are discussed briefly.

PMID- 10967715
TI  - [Experimental evidence of an antihypertensive and hypocholesterolemic effect of
      oil of argan, Argania sideroxylon].
AB  - The chronic ingestion of 5 ml/kg/d of Argan oil by spontaneously hypertensive
      rats restores normal blood pressure and induces hypocholesterolaemia. In order to
      confirm these results Meriones shawi, a rodent of the Gerbillideae family, was
      tested as a second animal model. Meriones submitted to a hypercaloric diet and
      physical inactivity became fat, and exhibited hypertension, dyslipidaemia and
      hyperinsulinaemia. When treated for two months with the same dosage regimen,
      decreases in glycaemia, total plasmatic cholesterol, LDL, insulinaemia and
      systolic and diastolic blood pressures of 4.4 per cent, 14.4 per cent, 32.5 per
      cent, 26.8 per cent, 28.8 per cent and 30.5 per cent were simultaneously
      observed. Increases in LDH and of TG of 27.9 per cent and 16.2 per cent
      respectively were also observed. No effect on body weight occurred. The action of
      polyunsatured fatty acids of the Argan oil is predominant, but in addition, other
      constituents play an active part.

PMID- 10967716
TI  - [Diuretic and hypotensive effects of Nigella sativa in the spontaneously
      hypertensive rat].
AB  - Nigella sativa (ranunculaceae) is used in Arab folk medicine as a diuretic and
      hypotensive plant. We report here the diuretic and hypotensive effects of
      dichloromethane extract of Nigella sativa seeds in the spontaneously hypertensive
      rat (SHR). An oral dose of Nigella sativa extract (0.6 ml/kg/day) and furosemide
      (5 mg/kg/day) increased significantly the diuresis by 16 and 30 per cent
      respectively after 15 days of treatment; urinary excretion of Cl-, Na+, K+ and
      urea is also increased. Simultaneously, the mean arterial pressure decreased
      respectively by 22 and 18 per cent in the Nigella sativa treated rat and
      nifedipine treated rat (0.5 mg/kg/day). In conclusion, the diuretic activity
      observed in the SHR rat treated with Nigella sativa seeds may be partially
      responsible for its diuretic action; it seems that other pathways may also be
      involved in their cardiovascular effects.

PMID- 10967717
TI  - [Consumption of performance-enhancing drugs by medical students in Nancy].
AB  - Medical students, who deal routinely with difficult studies and with patients,
      are not always prepared for this challenge. This may produce a specific and
      important source of stress. As a consequence, medical students may sometimes
      develop maladaptive responses, such as substance abuse. This study aimed to
      evaluate performance-enhancing drug use among medical students at the University
      Hospital of Nancy, France. A self-administered anonymous questionnaire was given
      to all 104 eighth-year residents. The 93 responding students (37 female and 56
      male), were aged 28.0 +/- 2.2 years (mean +/- SD); 53 per cent of the subjects
      reported enhancing-substance use in their first year of medical studies (72 per
      cent during preparation for their difficult examinations and 28 per cent
      throughout the year). The main substances were vitamins, anti-fatigue capsules,
      betablockers, marijuana (illicit drug) and benzodiazepines; 46 per cent of them
      were still using these drugs during the second to sixth years of their medical
      course. The main sources of drugs were retail pharmacists, with or without
      medical prescriptions. Could this use persist and lead to doctors with substance
      problems?

PMID- 10967719
TI  - [Drug interactions: a prospective pilot study in primary health care].
AB  - The present prospective pilot study investigated putative drug interactions in
      primary health care. Among 110 outpatients, 50 were treated with more than one
      drug (maximum = 10). Among these 50 prescription forms, 21 concerned at least one
      drug interaction, with a total of 47 different drug interactions. Most of them
      (94 per cent) were explained by a pharmacodynamic mechanism. They were classified
      as 'requiring use precautions' (64 per cent), 'to be taken into account' (25 per
      cent) or 'inadvisable' (11 per cent). None of them was 'contraindicated'. Most
      often the drugs involved were diuretics, converting enzyme inhibitors or non
      steroidal antiinflammatory drugs. Drug interactions, which concern around one in
      five prescription forms, remain an important topic in Clinical Pharmacology.

PMID- 10967718
TI  - [Adverse effects of contrast media: results of a 6 months study].
AB  - The use of iodinated contrast agents is associated with adverse drug reactions
      (ADRs) (mainly allergic). Data from the literature suggest a frequency of ADRs
      ranging from 5 to 8 per cent for the whole group of iodinated contrast agents.
      The present systematic prospective study performed over a period of six months
      investigated ADRs in a Radiology Department of the University Hospital in
      Toulouse. After 1480 injections of iodinated contrast agents, only five ADRs
      (i.e. 0.34 per cent) were observed. However, the frequency remained higher in
      patients with a history of allergy (1.5 per cent). The low frequency of ADRs can
      be explained both by the use of mainly low osmolality contrast agents (75 per
      cent) and by systematic preventive management of risk (detailed questionnaire,
      choice of the contrast agent according to risk).

PMID- 10967720
TI  - [Myocardial infarct and severe angina after antiproteases: 4 cases].

PMID- 10967721
TI  - [Polydrug intoxication with urapidil, bromazepam and chlorpromazine: case study].

PMID- 10967723
TI  - Health tips. Help for rectal itching.

PMID- 10967722
TI  - Coronary bypass surgery. Vital detours for the heart's blood supply.

PMID- 10967725
TI  - Anemia. A blood condition with many causes.

PMID- 10967726
TI  - Blepharoplasty. An eye-opening experience.

PMID- 10967724
TI  - New developments in osteoporosis treatment.

PMID- 10967727
TI  - Sprains. How to care for these common injuries.

PMID- 10967728
TI  - My wife and I take a multivitamin that contains iron. I've heard that too much
      iron can increase my risk of having a heart attack. Should I stop taking the
      iron?

PMID- 10967729
TI  - I've heard the term "placebo" used in news stories about research studies. What
      is it?

PMID- 10967730
TI  - Triage and initial evaluation of the oral facial emergency.
AB  - Essentially, emergency medicine encompasses the efficient application of limited
      resources to provide timely care to patients in health crisis. The appropriate
      triage, management, and disposition of patients with orofacial complaints
      requires systematic evaluation with attention to the ABCs. The first priority is
      to secure the airway. Once such a patient has been stabilized, a thorough
      examination, with documentation of the oropharyngeal and facial examination,
      should be conducted. Unfortunately, many conditions seen initially in the ED
      through patient self-referral ultimately require specialist care. Therefore,
      emergency physicians must temporarily provide pain relief and begin initial
      treatment of traumatic, infectious, or inflammatory conditions that await more
      definitive intervention. The emergency physician should consider it his or her
      role to exclude life threats, prevent complications, provide patient comfort, and
      ensure adequate and timely follow-up care.

PMID- 10967731
TI  - Important landmarks of the orofacial complex.
AB  - Hard-tissue and soft-tissue landmarks of the face and oral cavity are introduced.
      Definitions for anatomic structures are listed, and figures to aid clinical
      examination are provided. Relevance of these landmarks to examination, diagnosis,
      and function is made.

PMID- 10967732
TI  - Radiographic evaluation of the facial complex.
AB  - The patient with maxillofacial trauma presents a diagnostic challenge to the
      evaluating physician. Radiologic evaluation begins only after initial assessment
      and stabilization of the patient. Despite the advent of new-generation CT
      scanners, conventional radiography remains the diagnostic test of choice for
      initial evaluation of the maxillofacial skeleton. One should understand and be
      aware of the clinical value and interpretation of the standard radiographic
      facial and mandibular series, and panoramic radiography. Plain films can serve as
      a springboard, giving direction and orientation to CT when this is indicated.

PMID- 10967733
TI  - Assessment of patients with facial fractures.
AB  - One of the most demanding aspects of emergency medicine is the management of
      patients who have suffered facial trauma. The diagnosis and initial management of
      patients who have sustained traumatic facial injuries are discussed. The
      fundamentals required to assess patients with fractures of the facial skeleton
      and to make appropriate referrals are provided.

PMID- 10967734
TI  - Anesthesia and pain management.
AB  - Acute orofacial pain is usually managed by the administration of local
      anesthetics, systemic analgesics, or a combination of the two methods. In an
      emergency, intraoral maxillary nerve blockade is helpful for controlling pain in
      the midface, although infiltrations may be more suitable for discomfort
      originating from individual teeth or portions of the alveolar process. Mandibular
      anesthesia can be achieved by open or closed-mouth techniques for inferioral
      alveolar-lingual nerve blockade. Systemic pain relief is optimized by using full
      analgesic doses of NSAIDs, with opioids serving to increase the degree of
      analgesia if required, or to be used, often with acetaminophen, in patients
      intolerant to NSAIDs.

PMID- 10967735
TI  - Lacerations of the mouth.
AB  - Soft-tissue and bony injuries of the face and oral cavity constitute much of the
      trauma seen in the emergency department. These types of wounds can be frightening
      for patients. The management of patients with oral lacerations, including those
      of the oral mucosa, gingiva, tongue, and lip, is addressed.

PMID- 10967736
TI  - The swollen face. Severe odontogenic infections.
AB  - Owing to the widespread availability of preventive dental care and the
      development of effective antibiotics for the treatment of orofacial infection,
      the incidence of serious odontogenic infections has decreased dramatically over
      the past 50 years. Serious dental infections still occur, however, and their
      occasionally severe complications or even mortality warrant serious study of the
      clinical presentation, anatomy, and pathophysiology of orofacial infections. The
      goal of this review is to provide the emergency practitioner with a concise
      description of the clinical presentation, relevant anatomy, and treatment
      principles of odontogenic infection in the patient who presents to the ED with a
      swollen face or difficulty in opening the mouth widely. Prompt institution of
      surgical therapy for the infection, aided by appropriate antibiotic therapy
      enables the healthcare professions to continue their remarkable progress in
      treating these once-dreaded infections.

PMID- 10967738
TI  - Special considerations for the pediatric emergency patient.
AB  - Management of pediatric maxillofacial infections and trauma continue to challenge
      the clinician, because both conditions are uncommon. Therefore, individual
      clinicians might not see enough cases to formulate systematic and consistent
      treatment plans. When one is evaluating pediatric maxillofacial infections, the
      location of infection (upper or lower face) can serve as a diagnostic aid to
      develop a differential diagnosis and to initiate empiric treatment. When
      evaluating pediatric maxillofacial injuries while implementing acute treatment
      measures, the clinician should also be aware of the potential for late adverse
      sequalae owing to alteration of growth. In the absence of controlled studies,
      however, growth alternation from traumatic injuries to the facial skeletal
      remains a plausible but unproved hypothesis.

PMID- 10967737
TI  - Dentoalveolar trauma.
AB  - Dentoalveolar injuries represent a serious dental problem for the patient. Time
      from injury to treatment is a major factor in the outcome of many of these
      injuries. To decrease dental pain and suffering and enhance the prognosis,
      medical personnel must recognize the presence of dentoalveolar injuries and
      consult with, or refer the patient to, a dentist as soon as possible.

PMID- 10967739
TI  - Postsurgical complications.
AB  - The most common complications of oral surgery include bleeding, pain, swelling,
      infection, dry socket, and fracture. Bleeding can be controlled by applying gauze
      pressure to the area or through the use of hemostatic agents. A dry socket should
      have a dressing with eugenol applied, whereas a prescription for antibiotics or
      analgesics can take care of some of the other problems. Patients with fractures
      should be referred to a dentist or oral surgeon for treatment.

PMID- 10967740
TI  - Oral manifestations of systemic disease.
AB  - Many systemic diseases have associated oral symptoms. Occasionally, patients with
      these diseases present with lesions that occur primarily in the mouth. Although
      few systemic diseases have strictly pathognomonic lesions of the oral mucosa, a
      careful examination of the oral cavity can often lend important clues to making a
      diagnosis.

PMID- 10967741
TI  - Extraoral facial pain.
AB  - Craniofacial pain is a common chief complaint and is among the most frustrating
      diagnostic and treatment challenges encountered by emergency physicians. The
      efficient development of a differential diagnosis, the delivery of appropriate
      and effective therapies, and the appropriate referral of patients who present
      with craniofacial pain from extraoral sources are discussed. Disease
      descriptions, a diagnostic workup format, and acute management protocols are
      presented for the more common craniofacial pain entities.

PMID- 10967742
TI  - Orofacial considerations for pediatric, adult, and elderly victims of abuse.
AB  - Health care providers must take the time to educate themselves about domestic
      violence, its signs and symptoms, and the proper care of victims of child,
      spouse, or elder abuse. It is not enough to treat the immediate injuries without
      offering necessary and appropriate intervention on behalf of the victim. No one
      deserves to be beaten, sexually abused, or emotionally mistreated. If abuse is
      suspected, report it to the proper authorities. By focusing attention on this
      major health problem, physicians can provide a leadership role in using health
      care response to reduce the incidence of abuse and, ultimately, to save lives.

PMID- 10967743
TI  - Anesthesia management during cataract surgery.

PMID- 10967744
TI  - MMR vaccine and autism.

PMID- 10967745
TI  - Pest houses of Hertfordshire.

PMID- 10967746
TI  - Are drug proprietary names necessary?

PMID- 10967747
TI  - EU pharmacovigilance guidelines. Review.

PMID- 10967748
TI  - Free radicals as mediators of toxicity in Alzheimer's disease: a review and
      hypothesis.
AB  - Recent research has increasingly suggested a central role for free radical
      induced tissue damage in the pathogenesis of Alzheimer's disease (AD). In this
      paper we review evidence for the interaction between free radicals and other
      major factors/metabolic areas which have also been implicated in AD, including
      beta-amyloidosis, inflammatory cytokines, mitochondrial dysfunction and metal
      ions/homocysteine. We hypothesize that free radicals and antioxidants should not
      be considered in isolation in the aetiology and treatment of AD. It is the
      reciprocal induction and self-amplifying interplay between all of the above
      factors which is important in the pathogenesis of this disorder, and to which
      multi-pharmacological therapeutic strategies should be directed.

PMID- 10967749
TI  - Incidence, epidemiology, and etiology of esophageal cancer.
AB  - The precise causes of esophageal cancer have not been identified. A number of
      carcinogens and predisposing conditions have been implicated. There are
      pronounced differences between the demographic groups affected by squamous cell
      carcinoma and adenocarcinoma of the esophagus. Whereas the incidence of squamous
      cell carcinoma has remained constant, the incidence of adenocarcinoma of the
      esophagus has been rising steadily in recent years. The reasons for this trend
      remain unclear. Further studies of the molecular biology and epidemiology of this
      disease are needed.

PMID- 10967751
TI  - Clinical staging of esophageal carcinoma. CT, EUS, and PET.
AB  - CT is readily available to all patients. It is relatively inexpensive and fees
      are usually reimbursed. It provides exquisite anatomic detail of the chest and
      abdomen in patients with esophageal cancer. The only reliable use of CT in the
      determination of T is the exclusion of T4 tumors, which is suggested by the
      preservation of fat planes. Enlarged lymph nodes are suspicious for metastatic
      disease but require further study or tissue sampling if nodal metastases will
      determine treatment. Its major use is in the detection of distant metastatic
      disease; however, 30% to 60% of distant metastases may be radiographically
      occult. There is a significant learning curve for EUS staging of esophageal
      cancer. It is suggested that this study be performed at institutions where there
      is a dedicated, experienced endoscopic ultrasonographer with adequate
      instrumentation that allows specialty imaging and EUS-FNA. EUS is the best means
      of clinically determining T. The addition of EUS-FNA to routine EUS evaluation of
      lymph nodes allows an accuracy similar to the EUS determination of T. EUS has no
      purpose in assessment of non-nodal distant metastatic disease; however, the
      serendipitous finding of distant metastases in adjacent structures visualized
      during the evaluation of the primary tumor and lymph nodes has, on occasion,
      detected M1b disease. FDG-PET represents an advance over CT scanning in the
      screening for distant metastases. The major problems with FDG-PET staging of
      esophageal cancer is failure to detect metastatic deposits less than 1 cm in
      diameter and lack of anatomic definition. It is unable to determine T and has
      been inaccurate in the detection of lymph node metastases. Because this test is
      not readily available, is expensive, and is not routinely reimbursed, its use in
      staging esophageal cancer continues to be limited. Today, CT and EUS are the
      mainstays in the clinical staging of esophageal carcinoma. When possible, FDG-PET
      should be added to CT to improve the evaluation of non-nodal M1b disease. Results
      of these studies should determine the necessity for invasive staging techniques
      and direct their use.

PMID- 10967750
TI  - Molecular biology of esophageal cancer.
AB  - Several mechanisms of resistance to chemotherapy have been identified among the
      agents that are commonly used in the systemic treatment of patients with
      esophageal cancer: paclitaxel, platinum, and 5-FU. A recent study from our
      laboratory evaluated the initial endoscopic biopsy material from patients who
      subsequently underwent trimodality therapy, including chemotherapy with cisplatin
      and 5-FU, radiation therapy, and surgery. IHC analysis was performed on seven
      markers of chemotherapy or radiation therapy resistance: P-gp, GST-pi, MT
      (platinum inhibitors); EGF-R, TGF-alpha, erb-B2 (activation of cell growth
      cascade); and p53 (interferes with chemotherapy-induced apoptosis). In this
      study, elevated expression of GST-pi and P-gp were associated with decreased
      survival and may be markers of treatment resistance. Expression of erb-B2 was
      associated with enhanced survival and may be a marker of treatment sensitivity.
      Assessment of the probability of chemoresistance of a particular tumor using the
      expression of molecular biologic markers may allow for the selection of a more
      favorable chemotherapeutic agent. Furthermore, understanding the mechanisms of
      resistance, including the mechanisms of DNA repair, may provide insight into
      mechanisms to reverse or to inhibit resistance to chemotherapy. DNA repair
      mechanisms are used by cells to protect themselves against mutagens and
      carcinogens. DNA repair inhibitors may increase the mutagenicity associated with
      DNA damage and may prove to be an ineffective oncologic treatment strategy;
      however, the possibility exists that DNA repair inhibition may improve the
      efficacy of anticancer agents, and this should be tested. The value of this
      strategy may be in allowing treatment doses to be decreased and lessening side
      effects while maintaining therapeutic efficacy.

PMID- 10967752
TI  - Surgical staging of esophageal cancer.
AB  - The rising incidence of adenocarcinoma of the esophagus and the poor overall 5
      year survival using current treatment regimens make it essential that clinical
      trials continue to search for more effective regimens for specific stages of
      esophageal cancer. It is clear from work in non-small cell lung cancer that
      clinical efficacy for platinum-based chemotherapeutic regimens has shown promise
      only in specific subsets of patients, such as those with stage IIIa tumors, but
      no benefit at all for earlier stages. In lung cancer, mediastinoscopy has been
      shown to be the most accurate method to stage locoregional lymph nodes and is
      considered to be the gold standard for clinical trials. In esophageal cancer,
      accurate surgical staging of all locoregional lymph nodes is more complex and may
      involve abdominal, thoracic, and cervical areas. Molecular evidence of lymph node
      involvement in esophageal cancer suggests that even histologically negative nodes
      may harbor micrometastases in a significant number of cases. Laparoscopy and
      thoracoscopy now offer a more accurate alternative to conventional staging of
      esophageal cancer. For distal esophageal cancers near the gastroesophageal
      junction, laparoscopic staging alone may suffice in most cases. Associated costs
      and the requirement for a surgical procedure should encourage the continued
      evaluation of new noninvasive modalities and the further evolution of endoscopic
      ultrasound. Currently, we recommend the application of minimally invasive
      surgical staging to assess new noninvasive technologies, such as PET scanning,
      and for use in clinical trials until the definitive approach to staging
      esophageal cancer is established. We are currently participating in an ongoing
      multicenter study of thoracoscopic and laparoscopic staging for esophageal
      cancer.

PMID- 10967753
TI  - The current role of transhiatal esophagectomy.
AB  - Transhiatal esophagectomy is gaining increasing use as the preferred technique
      for esophagectomy. In this article, the indications, diagnostic evaluation, and
      technical details of the operative procedure for transhiatal esophagectomy are
      reviewed. Results of large clinical series are discussed and the potential
      pitfalls and risks of the procedure are reviewed. Current controversies and
      future trends are also discussed.

PMID- 10967754
TI  - Esophagectomy. The role of the intrathoracic anastomosis.
AB  - Esophagectomy for carcinoma continues to play a vital role in the treatment of
      patients with esophageal carcinoma. Safe resection with minimal short-term
      mortality and good swallowing palliation can be performed via the use of
      multiple, well-described resection techniques. Tumor location and the possibility
      of direct mediastinal invasion may dictate the need for transthoracic dissection
      and extension of the resection to the cervical esophagus for ideal margins.
      Differences in survival, short-term outcome, and swallowing function have yet to
      be proven for procedures with extended lymph node dissection versus those with
      minimal intrathoracic or cervical node dissections. The surgeon's ability and
      familiarity with various techniques may enhance the overall treatment of the
      patient with esophageal carcinoma as their treatment becomes more directed by the
      initial pathologic stage at presentation.

PMID- 10967755
TI  - The three-hole esophagectomy. The Brigham and Women's Hospital approach (modified
      McKeown technique).
AB  - The three-incisional technique described above allows the surgeon to do a safe
      resection that includes a complete lymphadenectomy and a cervical esophagogastric
      anastomosis. The advantages of a neck anastomosis have been detailed elsewhere
      and briefly include a lower incidence of reflux symptoms, a more extensive
      proximal resection margin, position outside prior radiation ports, and easier
      management of an anastomotic leak should it occur. By performing this in two
      phases, the operation can be performed efficaciously. The subtle nuances
      detailed, such as the use of Penrose drains and the arthroscopic camera bag to
      deliver the specimen, help to avoid some of the potential complications generally
      associated with an esophagectomy.

PMID- 10967756
TI  - Three-field lymphadenectomy for esophageal cancer.
AB  - Esophagectomy with three-field lymph node dissection can be performed with a
      mortality and morbidity similar to that of less extensive operations.
      Approximately one third of patients will have previously unsuspected metastasis
      to the recurrent laryngeal nodes. This pattern of spread seems to be independent
      of cell type or tumor location. The impact of the procedure on patient survival
      is unclear; however, our early results are encouraging.

PMID- 10967758
TI  - Radiation therapy for esophageal cancer.
AB  - Radiation therapy continues to play a major role in the management of patients
      with esophageal carcinoma. This role continues to evolve based on the success of
      combined modality treatment regimens. During the past decade, the concurrent
      application of chemotherapy and radiation has gained acceptance as a standard of
      practice that offers patients an improved opportunity for long-term survival,
      whereas the ultimate benefit of trimodality therapy remains an unanswered
      question. The start of the twenty-first century brings the challenge of
      decreasing the toxicities associated with therapy and the need to improve
      therapeutic options. The recent advances in technology have positioned radiation
      oncology to achieve both of these goals.

PMID- 10967757
TI  - Recent developments in the chemotherapy of advanced esophageal cancer.
AB  - Several new agents developed in the past decade have demonstrated activity in
      esophageal cancer. No single agent or combination of agents has been compared in
      a randomized study with the current standard, albeit limited, treatment of
      cisplatin and 5-FU. Recent studies employing instruments measuring pain and
      quality of life have demonstrated stability or improvement, indicating real
      patient benefit from treatment. Numerous agents with potential activity in
      esophageal carcinoma based on their putative mechanisms of action are in
      development. Only clinical trials can establish the role of these agents in the
      clinic.

PMID- 10967759
TI  - Clinical trials for esophageal carcinoma.
AB  - Progress is being made in the treatment of this usually fatal disease. Clinical
      trials are essential to define the role of chemotherapy, radiation, and surgery
      in the treatment of esophageal cancer, and hopefully, with continued enthusiasm
      within the surgery community, these trials can be completed within a reasonable
      period of time.

PMID- 10967761
TI  - Palliation of dysphagia.
AB  - This article discusses the diagnosis and interventional options apart from
      surgical resection for carcinoma of the esophagus. Other topics discussed are
      methods of inserting plastic and self-expanding metal stents in conjunction with
      their complications, and neodymium:yttrium-aluminum-garnet photodynamic therapy,
      cryoablation, and BICAP (bipolar cautery probe) options. Clinical scenarios
      illustrate the pros and cons of these approaches.

PMID- 10967760
TI  - The role of multimodality therapy for esophageal cancer.
AB  - One trial has suggested improved survival with preoperative chemotherapy and
      radiation therapy with acceptable morbidity and mortality. Other studies have not
      demonstrated apparent improvement in survival, although the protocols are
      somewhat different. Longer follow-up is needed in these preliminary studies, and
      well-designed, prospective, multicenter randomized trials are necessary in the
      future. These studies should compare identical CRT and surgery regimens and
      identify a group of esophageal patients that might benefit from preoperative
      chemotherapy or radiation therapy. In order to evaluate the results of future
      trials without bias and to determine which group of esophageal patients will
      benefit from preoperative CRT, pretreatment, accurate TNM staging by CT and EUS
      combined with pathologic LN staging when possible will be crucial in future
      trimodality therapy trials for esophageal cancer. The investigation of biologic
      molecular markers to predict chemoradiation sensitivity and prognosis deserves
      careful exploration. Unfortunately, those patients without a response do not
      benefit from the preoperative chemotherapy but still may suffer the associated
      toxicity. These patients may have a much higher risk of postoperative fatal
      complications including respiratory failure, bone marrow suppression, and sepsis.
      It has been shown that CR patients in the chemotherapy/surgery group survive
      longer than nonresponders; it would be helpful to find useful molecular
      biomarkers to identify chemotherapy-sensitive patients before the preoperative
      chemotherapy is employed. Several pilot trials are underway using chemotherapy
      sensitivity testing on the endoscopic biopsy specimen before the chemotherapy is
      applied.

PMID- 10967762
TI  - Photodynamic therapy for esophageal cancer. Update.
AB  - Although clinical studies with photodynamic therapy have been conducted for over
      25 years, only recently has this technique become widely available for the
      treatment of esophageal cancer. Studies have demonstrated that it is as effective
      as Nd:YAG therapy for advanced esophageal malignancies while technically being
      somewhat easier to perform. Preliminary studies in early esophageal cancer also
      show effectiveness. In many ways, PDT is still in its infancy, and its exact role
      compared to other endoscopic treatments of esophageal cancer remains to be
      defined. It is expected that the development of new photosensitizers and light
      delivery systems will further expand the role of PDT in the diagnosis and
      management of esophageal neoplasms.

PMID- 10967763
TI  - Long-term outcomes following esophagectomy.
AB  - Improving postesophagectomy outcomes results in fewer long-term sequelae.
      Research with this population has shown a correlation between physical symptoms
      and quality of life. Provider awareness of common postesophagectomy conditions,
      such as post-thoracotomy pain, vocal cord paralysis, altered gastric emptying,
      and dysphagia, can expedite appropriate treatment and referrals. Prompt symptom
      management, consistent psychosocial support from clinicians, and contact with
      other patients and families can decrease feelings of stress and isolation in
      patients and family caregivers.

PMID- 10967764
TI  - Role of fluoride in oral health promotion.
AB  - Fluoride has played a pivotal role in oral health promotion over the past 50
      years. This paper reviews key issues currently impacting on the role of fluoride
      in preventing dental caries. The understanding of the process of dental caries
      and the mode of action of fluoride has changed in recent years. Dental caries is
      a continuous process of demineralisation and remineralization of the enamel and
      fluoride plays a key role in this process through its action at the plaque enamel
      interface. It is now accepted that the primary mode of action of fluoride is post
      eruptive. The post-eruptive action of fluoride has resulted in new methods of
      delivering fluoride. The paper discusses the impact of these new methods of
      delivering fluoride on total fluoride intake in children and on the prevalence of
      dental fluorosis. The role of different methods of delivering fluoride both on a
      community and individual basis is presented and recommendations are outlined.

PMID- 10967765
TI  - Oral hygiene in the prevention of caries and periodontal disease.
AB  - While some periodontal disease may be as old as mankind itself, caries as a
      public health problem appeared with the development of flour and sugar mills, and
      the universal access to fermentable carbohydrates. As a consequence, during the
      last 500 years caries and periodontal disease have been the most common diseases
      afflicting the human mouth. Together, these two diseases have been responsible
      for untold pain and suffering, and for excessive destruction and loss of people's
      teeth. With improving social circumstances in most industrialised nations,
      increased availability and affordability of modern oral health care, and the
      promotion of conservative treatment concepts, the 20th century saw significant
      progress in eliminating pain and tooth loss. Moreover, during the last 50 years
      advances in the oral health sciences and in technology, have not only increased
      our understanding of the nature of these diseases and their causes, but also
      introduced and tested new approaches to their prevention.

PMID- 10967766
TI  - Saliva in health and disease: an appraisal and update.
AB  - Saliva plays an important role in oral health monitoring, regulating and
      maintaining the integrity of the oral hard tissues and some soft tissues. This
      paper reviews the role of saliva, the prevalence of oral dryness and the
      consequent importance of salivary flow as well as the relationship between
      xerostomia and salivary gland hypofunction amongst the causes of oral dryness.
      Other aspects of oral conditions associated with saliva are also reviewed
      including Sjogren's Syndrome and oesophageal function. Finally, knowledge, and
      the current use of salivary tests and the utilisation of saliva as a diagnostic
      fluid are surveyed.

PMID- 10967767
TI  - Diet and oral health.
AB  - This review paper looks at the effects of diet on oral health and is concerned
      mainly with the effects of localised attacks on the dental hard tissues. In
      analysing the epidemiological evidence, the paper draws distinctions between the
      rates of diseases entities in developed and developing countries. The author
      concludes that oral health risks do not necessitate dietary recommendations in
      addition to, or other than, those required for maintenance of general health. The
      paper indicates an increasing need for evidence-based, individual tailor-made
      counselling and for specific programmes directed towards defined, high-risk
      groups or populations whose oral health problems have been carefully studied and
      identified.

PMID- 10967768
TI  - The central phobic position: a new formulation of the free association method.
AB  - The author discusses a particular quality of associative behaviour observed in
      some borderline patients, and its role in maintaining a central defensive
      position, clearly discernible in a complex use of the analyst, and a particular
      functioning of the mind that the author terms phobic. Illustrating his argument
      with a detailed clinical account of the gradual joining of associative themes in
      one particular patient, the author both demonstrates the theory underlying his
      practice and exemplifies the deeper theoretical underpinning of his approach to
      psychoanalysis. This implies a new formulation of the free association method. By
      constructing an analytic space in which free association and psychoanalytic
      listening are possible, the analyst can voice and link previously catastrophic
      ideas, quite unknown to the patient's consciousness, to help the patient to
      create meaning and obtain relief from previously dominant but unknown terrors.
      Concluding his paper, the author links his clinical account both to his ideas on
      temporality and negativity and to the relationship between oedipal and pre
      oedipal elements.

PMID- 10967769
TI  - Symbols and their function in managing the anxiety of change: an intersubjective
      approach.
AB  - The author suggests that change inevitably creates anxiety because of loss and
      confrontation with the unknown. It is proposed that one function of symbols is to
      manage the anxiety of change. They do this by creating a means by which anxieties
      can be presented to the subject and then communicated to another mind. These
      creations are called symbolic because, it is proposed, their purpose is the
      communication as well as the incorporation of internal anxieties and desires with
      external exigencies, which might be termed symptoms. Viewing them in this way
      enables the analyst to put symbolic phenomena as they emerge in an analysis into
      an intersubjective perspective. The author suggests that thinking of symbols as
      purely intrasubjective phenomena limits our perspective. It is more technically
      useful to look at the communicative aspects of symbols as they present themselves
      to the symbolising subject; and, subsequently, to the analyst in the dialogue
      within the psychoanalytic setting because the objective and temporal dimension of
      the setting can thereby be included. Two clinical examples of symbols are
      discussed, one that was brought for analysis and a second that developed in the
      course of an analysis. One is given as an example of resistance to change,
      whereas the other revealed an unconscious drive for change.

PMID- 10967770
TI  - Shared life narratives in the work of Lou Andreas-Salome.
AB  - The author presents a re-reading of the works of Lou Andreas-Salome (1861-1937),
      one of the key figures in the early history of psychoanalysis. He focusses in
      particular on her biographical and autobiographical works, as well as her
      correspondences with Freud, Rilke and other influential people of her time,
      arguing that Andreas-Salome disappears from her own works as an autonomous
      speaking subject, while reappearing in the works of others as a silent, tacit
      influence. On closer examination, a specific genre emerges from her works that
      has so far gone unnoticed: the shared life narrative. The author claims that
      Andreas-Salome developed this genre of shared life narratives in an attempt to
      match her theoretical notions of narcissism to a practical communicative position
      that is neither subjectivistic nor objectivistic. Relating the notion of shared
      life narratives to the psychoanalytic discourse, new possibilities may be opened
      up for expanding and enlarging our knowledge of human interaction.

PMID- 10967771
TI  - Freud's different versions of forgetting 'Signorelli': rhetoric and repression.
AB  - The author examines Freud's three written accounts of his forgetting of the name
      'Signorelli'. The three texts--a letter to Fliess, an early scientific article
      and a chapter in 'The Psychopathology of Everyday Life'--contain significant
      differences that are examined in detail. In describing the incident, Freud made
      successive changes that were matched to his theoretical explanations for the
      forgetting. More than this, close examination of the differences between the
      versions offers clues about Freud's own personal feelings that he was seeking to
      avoid exposing to his readers, while discussing the reasons for his slip of
      memory. It is suggested that Freud's thoughts are likely to have included his
      ambivalent feelings towards the death of his father, his sense of Jewishness and
      his relations with his sister-in-law, with whom he had been travelling when he
      had seen Signorelli's frescoes at Orvieto. Freud's other associations with
      Orvieto are examined. It is argued that the different versions of the episode
      represent a means by which Freud himself repressed uncomfortable thoughts exposed
      during his self-analysis. As such, this paper provides evidence for a discursive
      interpretation of repression.

PMID- 10967772
TI  - The borrowed sense of guilt.
AB  - An enquiry into the aetiology and dynamics of the borrowed sense of guilt is
      attempted, using selected material from three adult analytic cases. The author
      describes the tendency for the borrowed sense of guilt to develop in children
      where there is an extremely narcissistic family member, usually a parent, with a
      marked tendency to externalize his or her own guilt. The child develops a massive
      denial of being so used and so little loved by the parent and is trained into
      accepting the externalized guilt, through long repetition of interactions with
      the narcissistic family member, in which a terror of abandonment acts as a
      primary motivator. As development progresses a further powerful dynamic develops
      that keeps the borrowed sense of guilt in place: it is used by the child as a
      buttress for his or her denial of the lack of love shown in the relationship. 'I
      must be the guilty one, and if I just change my behaviour the relationship should
      be fine', is what the child says to him- or herself.

PMID- 10967773
TI  - Can we do psychoanalytic outcome research? A feasibility study.
AB  - Despite the widespread use of long-term psychodynamic treatments,
      methodologically rigorous outcome studies have not been conducted. The authors
      describe the results of a feasibility study designed to (1) investigate whether
      patients in psychodynamic treatment, including psychoanalysis, could be recruited
      and retained as research subjects, (2) determine patient and therapist compliance
      with self-report measures, rater-administered structured interviews and session
      audiotaping and (3) obtain pilot data on changes in these measures after one year
      of treatment. Nine patients entering psychoanalysis and fifteen entering
      psychodynamic psychotherapy were studied at baseline, six months and one year.
      Major findings were as follows: (1) recruitment rates were 27% (psychoanalysis)
      and 83% (psychotherapy), (2) all patients who remained in treatment remained in
      the research protocol, (3) drop-out rates among research participants and non
      participants were equivalent, (4) current Axis I (usually affective or anxiety)
      disorders were found in over 60% of patients, (5) Axis II disorders in the
      absence of current Axis I disorders were rare, (6) despite a small number (N) of
      participants, significant positive change was demonstrated on a variety of
      measures after one year. Results suggest that it is possible to demonstrate a
      therapeutic effect of psychodynamic treatments, including psychoanalysis, but
      changing negative clinical perceptions of research is necessary if
      methodologically rigorous outcome studies are to be possible in the future.

PMID- 10967774
TI  - From sixty-two interviews on 'the worst and the best episode of your life'.
      Relationships between internal working models and a grammatical scale of subject
      object affective connections.
AB  - The authors address the issue of inferring unconscious internal working models of
      interaction through language. After reviewing Main's seminal work of linguistic
      assessment through the 'adult attachment interview', they stress the idea of
      adults' internal working models (IWMs) as information-processing devices, which
      give moment-to-moment sensory orientation in the face of any past or present,
      animate or inanimate object. They propose that a selective perception of the
      objects could match expected with actual influence of objects on the subject's
      self, through very simple 'parallel-processed' categories of internal objects.
      They further hypothesise that the isomorphism between internal working models of
      interaction and grammatical connections between subjects and objects within a
      clause could be a key to tracking positive and negative images of self and other
      during discourse. An experiment is reported applying the authors' 'scale of
      subject/object affective connection' to the narratives of sixty-two subjects
      asked to write about the 'worst' and 'best' episodes of their lives. Participants
      had previously been classified using Hazan & Shaver's self-reported 'attachment
      types' (avoidant, anxious and secure) categorising individuals' general
      expectations in relation to others. The findings were that the subject/object
      distribution of positive and negative experience, through verbs defined for this
      purpose as either performative or state verbs, did significantly differ between
      groups. In addition, different groups tended, during the best episodes,
      significantly to invert the trend of positive/negative subject/object
      distribution shown during the worst episode. Results are discussed in terms of a
      psychoanalytic theory of improvement through co-operative elaboration of negative
      relational issues.

PMID- 10967775
TI  - The primary process and the unconscious: experimental evidence supporting two
      psychoanalytic presuppositions.
AB  - The authors report on two experiments designed to test an important feature of
      the primary process: unconscious categorisation by attributes rather than by
      relations. These experiments were designed to provide support, independently of
      the clinical situation, for the presupposition of a psychological unconscious and
      for the presupposition that unconscious mentation is organised along primary
      process lines. Their results were encouraging. They found that (1) unconscious
      similarity judgements could be made; and (2) these judgements were based on
      attributes (a primary-process mechanism) rather than relationships (a secondary
      process mechanism). This independent evidence, obtained in controlled
      experimental studies supporting two fundamental psychoanalytic presuppositions,
      should be welcome news to psychoanalysts, given the continuing criticism from
      many quarters that basic psychoanalytic ideas lack independent validation. This
      paper begins with an overview of the primary processes with a special focus on
      the role of categorisation by attribute, the particular aspect of primary process
      explored in this study. Next a brief history of previous empirical investigations
      of primary process is given, following which the current experiments are
      presented.

PMID- 10967777
TI  - Rage in the analytic setting.

PMID- 10967776
TI  - Clinical and theoretical uses of bi-logic: presentations in honour of Matte
      Blanco.

PMID- 10967779
TI  - The role of affect in motivation.

PMID- 10967778
TI  - Erna and Melanie Klein.

PMID- 10967780
TI  - Between ourselves: philosophical conceptions of intersubjectivity.

PMID- 10967781
TI  - Memory and therapeutic action.

PMID- 10967782
TI  - On James Herzog's 'Blood and love'.

PMID- 10967783
TI  - 'The unconscious and psychosis: some considerations on the psychoanalytic theory
      of psychosis' by Franco De Masi.

PMID- 10967784
TI  - The cultural and institutional context of Habermas's view of psychoanalysis.

PMID- 10967785
TI  - Controversies in psychoanalytic education: the issue of race and its relevance in
      psychoanalytic treatment.

PMID- 10967786
TI  - Psychoanalysis on stage: Moss Hart's Lady in the dark.

PMID- 10967788
TI  - A derailed dialogue: unexpected difficulties in the psychoanalytic work with
      patients from East Germany.

PMID- 10967787
TI  - Blaming Bettelheim.

PMID- 10967789
TI  - Janacek and Sibelius: the antithetical fates of creativity in late adulthood.

PMID- 10967790
TI  - Breast cancer: risk factors, screening, and prevention.
AB  - OBJECTIVES: To provide a review of the major and minor risk factors for the
      development of breast cancer and the options for prevention and treatment in
      women at high risk for breast cancer. DATA SOURCES: Clinical and research
      articles and textbooks. CONCLUSIONS: Breast cancer is the leading cancer found in
      women in the United States. For high-risk women, understanding their risk,
      appropriate screening recommendations, and possible prevention strategies is
      paramount. IMPLICATIONS FOR NURSING PRACTICE: Through education and psychosocial
      support, the nurse can assist with decision-making regarding risk reduction and
      current prevention and treatment options.

PMID- 10967791
TI  - New diagnostic techniques and treatments for early breast cancer.
AB  - OBJECTIVES: To review diagnostic techniques and treatments for early breast
      cancer, including radiologic techniques, biomarkers, surgical techniques,
      radiation therapy, adjuvant chemotherapy regimens, and hormonal therapy. DATA
      SOURCES: Scientific and review articles, book chapters, and clinical practice.
      CONCLUSIONS: Breast cancer is a major health problem. The advances in diagnosis
      and treatment of early breast cancer and the amount of information available make
      it difficult for patients to make diagnostic and treatment decisions.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses need to be knowledgeable in
      the many advances in diagnostic and treatment techniques for early breast cancer
      to assist patients with difficult decisions.

PMID- 10967792
TI  - Issues in the treatment of metastatic breast cancer.
AB  - OBJECTIVES: To provide a discussion of the treatment of metastatic breast cancer,
      nursing interventions, and quality of life issues for women with advanced breast
      cancer. DATA SOURCES: Journal articles and internet web sites. CONCLUSIONS:
      Advances in the discovery of new chemotherapeutic regimens, monoclonal
      antibodies, and bisphosphonates have offered more options for the treatment of
      metastatic breast cancer. Treatment is aimed at improving survival while
      maintaining quality of life. IMPLICATIONS FOR NURSING PRACTICE: Nurses can use
      this information to educate patients about their cancer treatment. It provides
      nurses with strategies for management of treatment side effects and will enhance
      their understanding of quality of life issues for women with metastatic breast
      cancer.

PMID- 10967793
TI  - Advanced breast cancer: recent developments in hormonal therapy.
AB  - OBJECTIVES: To review recent developments in hormonal therapy for metastatic
      breast cancer. DATA SOURCES: Published books and articles. CONCLUSIONS: Newer
      hormonal agents are offering women alternatives for sequential therapy of
      metastatic disease that provide benefit with less risk. IMPLICATIONS FOR NURSING
      PRACTICE: A thorough understanding of the relationship between hormonal
      influences and breast cancer will assist nurses to better appreciate the variety
      of agents now available and their specific indications, outcomes, and effects.
      Common side effects include weight gain, hot flashes, nausea, and skin and
      vaginal changes. Nursing efforts focus on the areas of body image disturbance,
      side effect management, and fostering healthy relationships.

PMID- 10967794
TI  - Hot flashes and their management in breast cancer.
AB  - OBJECTIVES: To review literature relevant to defining and managing hot flashes in
      women with breast cancer. DATA SOURCES: Published literature on hot flashes in
      women with breast cancer and in healthy women. CONCLUSIONS: The etiology of hot
      flashes is influenced by several breast cancer treatment-related factors. Hot
      flashes are a prevalent, severe problem that can negatively impact quality of
      life. Certain women are at higher risk for hot flashes following breast cancer
      treatment. Little research supports the safety or effectiveness of treatments in
      women with breast cancer. IMPLICATIONS FOR NURSING PRACTICE: Implications include
      the need to improve patient education, perform comprehensive symptom assessments,
      and counsel women about various treatment alternatives.

PMID- 10967796
TI  - Culture as an influence on breast cancer screening and early detection.
AB  - OBJECTIVES: To explore how culture may play a part in breast cancer screening,
      early detection, and efforts to decrease breast mortality. DATA SOURCES: Journal
      articles published in the past 20 years on cultural aspects of cancer prevention
      and control. CONCLUSIONS: Research seems directed more at discovering cultural
      differences than at identifying similarities on how culture influences breast
      cancer screening and early detection. The influences of poverty and lack of
      educational opportunities account for much of what is termed cultural difference.
      IMPLICATIONS FOR NURSING PRACTICE: Improving practice through an informed
      understanding of culture calls for considerable self-education and a fundamental
      refinement of care delivery.

PMID- 10967795
TI  - Lymphedema in women treated for breast cancer.
AB  - OBJECTIVES: To review the clinical and evidence-based knowledge of lymphedema in
      women treated for breast cancer, including the anatomy, physiology,
      pathophysiology, diagnosis, management, and nursing role. DATA SOURCES: Research
      studies, review articles, clinical literature, American Cancer Society lymphedema
      work group proceedings. CONCLUSIONS: Arm lymphedema can be a consequence of
      treatment for breast cancer and may affect all aspects of quality of life at any
      time during recovery and long-term survivorship. Prevention and early treatment
      are vital. IMPLICATIONS FOR NURSING PRACTICE: As patient advocates, nurses can
      document patient complaints, conduct arm assessments, and reinforce arm
      precautions at every clinical visit. Knowledge of research and treatment advances
      is crucial to enhancing the quality of life of women treated for breast cancer.

PMID- 10967797
TI  - XIII international AIDS Conference: new thoughts on treatment in all worlds.

PMID- 10967798
TI  - Selected topics from the XIII International AIDS Conference.

PMID- 10967799
TI  - Improving outcomes and managing costs of care: from the XIII International AIDS
      Conference.
AB  - Taken as a group, these presentations endorse a treatment strategy that should
      improve outcomes for patients as well as manage the high costs of antiretroviral
      therapy. A combination of strategies that balances antiretroviral therapy with
      convenient, compact regimens and the use of new technologies such as viral load
      monitoring, therapeutic drug levels, and resistance testing can lead to improved
      outcomes such as fewer hospitalizations and decreased mortality. Wrapped around
      this strategy is an adherence program that assesses adherence and provides
      treatment support by helping patients overcome the myriad barriers to adherence.
      When one compares the treatment of HIV in developed nations with that in
      underdeveloped nations, the contrasts can be sobering and stark as evidenced by
      the descriptions of the significant barriers to treatment in other parts of the
      world. It is clear that while we still have significant barriers to treatment in
      the United States, the rest of the world looks to us for answers on how to make
      treatment accessible and cost-effective.

PMID- 10967800
TI  - Hoax-busting Web site created by CDC.

PMID- 10967801
TI  - Alarming incidence of new HIV infections raises fears of scourge to come.

PMID- 10967802
TI  - Vaccine based on HIV subtype A.

PMID- 10967803
TI  - Botswana AIDS partnership is formed.

PMID- 10967804
TI  - Emerging HIV drug resistance in Africa.

PMID- 10967805
TI  - Clinical data released on ABT-378/r.

PMID- 10967806
TI  - A physician's primer to antiretroviral drug resistance testing.
AB  - Evaluating the genetic composition of HIV has evolved from a traditional
      epidemiologic research tool into a widely used clinical asset in the management
      of HIV infection. Genotypic and phenotypic testing is designed to identify drugs
      less likely to be therapeutically effective. Genotypic assays identify specific
      "gene mutations" or nucleotide substitutions known to confer drug resistance,
      whereas phenotypic assays measure the amount of drug necessary to inhibit viral
      replication in vitro. Prospective studies of antiretroviral drug resistance
      testing have shown its value as an independent predictor of optimal virologic
      response to drug therapy. Current guidelines recommend use of these tests
      following treatment failure and during pregnancy; considerations for testing
      include primary infection and treatment-naive patients. The identification of
      drug resistance can help the clinician individualize treatment regimens to attain
      maximal viral suppression and patient longevity.

PMID- 10967807
TI  - HIV resistance testing--has it come of age?

PMID- 10967808
TI  - Switching from a PI-based to a PI-sparing regimen for management of metabolic or
      clinical fat redistribution.
AB  - Concerns regarding metabolic perturbations occurring during protease inhibitor
      (PI)-based regimens have led to investigation of switching from a PI-based to a
      non-nucleoside reverse transcriptase inhibitor- or abacavir-based regimen. There
      appear to be considerable benefits to switching from a PI-based regimen to one of
      these PI-sparing regimens. In particular, patients appear generally pleased with
      the improved administration characteristics of the new regimens, and improvements
      in quality of life have been reported. However, resolution of the metabolic
      abnormalities that may arise during PI therapy is incomplete. Peripheral or
      subcutaneous fat mass improvements are not evident in the studies reported to
      date. Weight gain, probably in part due to removal of PI-related dietary
      restrictions, has been observed and may lead to improvements in appearance.
      Maintenance of virologic control varies among studies but is generally in the
      range of 85% to 100% of the patients receiving the PI-sparing regimen. The extent
      of prior drug exposure (or drug resistance) in patients entering the studies may
      be a key risk factor for loss of virologic control.

PMID- 10967809
TI  - Antiretroviral switching studies--the jury is still out.

PMID- 10967810
TI  - AIDS-related primary CNS lymphoma: a brief review.
AB  - Primary CNS lymphoma, which has a strong association with Epstein-Barr virus, was
      increasing in incidence in patients with AIDS before the introduction and
      widespread use of combination antiretroviral therapy. The diagnostic strategies
      for primary CNS lymphoma, including contrast-enhanced CT or MRI and brain biopsy,
      are well established. The use of a combination of diagnostic tools to reduce the
      need for brain biopsy is currently being evaluated. The clinical outcome with
      current treatments for primary CNS lymphoma in HIV-infected persons remains
      relatively discouraging.

PMID- 10967811
TI  - Thromboembolism associated with HIV infection: a case report and review of the
      literature.
AB  - The array of the clinicopathologic spectrum related to HIV infection continues to
      increase and present new challenges to physicians caring for HIV-infected
      patients. Recent literature is encumbered with reports of various abnormalities
      consistent with a hypercoagulable state leading to thromboembolic complications.
      The coexistence of HIV/AIDS-related illnesses, such as malignancies,
      opportunistic infections, or autoimmune diseases, as well as drug therapy, may
      also predispose HIV-infected patients to thromboembolic disease. A case report of
      a 39-year-old man with Kaposi sarcoma who developed pulmonary embolism is
      presented, along with a review of the literature.

PMID- 10967812
TI  - Impact factor.

PMID- 10967813
TI  - Silence surprising.

PMID- 10967814
TI  - Definition outdated.

PMID- 10967815
TI  - Delights of a dental career.

PMID- 10967816
TI  - Concerns addressed.

PMID- 10967817
TI  - Trial dentures, insertion of processed dentures and review of complete dentures.

PMID- 10967818
TI  - Dental bodies corporate--a trip through the legislation.
AB  - A review of the legislation and regulation impacting upon Dental Bodies
      Corporate. This includes consideration of the Dentists Act 1984; the GDC Rules
      and Regulations made there under; and current ethical guidance issued by the GDC.

PMID- 10967819
TI  - What the papers say: how does the United Kingdom press treat water fluoridation
      and does it matter?
AB  - This is a case study to investigate in an objective way how fluoridation is
      reported in the press. All press cuttings collected by a reputable national
      agency covering a 9-month period were studied; were rated as being
      profluoridation, antifluoridation or neutral. The rating system was calibrated
      before the study by comparing the scores given by the author and a selected group
      of experts. Overall, press article coverage was antifluoridation, though it is
      not clear how intentional this is.

PMID- 10967820
TI  - What patients think of dental services.
AB  - In 1998, research on 'What the general public wants from the general dental
      service' was carried out by the Centre for Dental Services Studies (CDSS) at the
      University of York and was commissioned by the British Dental Association (BDA).
      The research culminated in the report: 'User Priorities for General Dental
      Services'. This article outlines the main message from the research and contains
      the researcher's personal observations.

PMID- 10967821
TI  - Career patterns of dental hygienists in Scotland.
AB  - OBJECTIVE: To study career patterns of dental hygienists in Scotland. SUBJECTS
      AND METHODS: Questionnaires were sent to all the dental hygienists enrolled with
      the General Dental Council in 1998 who had addresses in Scotland and those who
      were alumni of Scottish School of Dental Hygiene within the past 10 years.
      RESULTS: There was a 58.7% response (334 out of 569). A net loss of trained
      hygienists was not found. The results suggested that most would remain in
      employment for at least 30 years and about a third would retire early. Half were
      in full-time employment and 60% had been in continuous employment. Most of the
      remainder had personal reasons for ceasing work. 39% had refused employment
      because of the poor level of pay. CONCLUSIONS: The introduction of the 2-year
      course has reduced output from schools of dental hygiene and demand for
      hygienists is high. Little hard information exists to support manpower planning
      in this area. This study suggests that there is little wastage of trained dental
      hygienists in Scotland. More data is required concerning employment opportunities
      and potential unmet demand for this group of PCDs to establish the number of
      training places required.

PMID- 10967822
TI  - Repeat general anaesthesia for paediatric dentistry.
AB  - AIMS: To investigate patterns of referral, disease and treatment for healthy
      children who had received two or more dental general anaesthetics (DGA) for
      exodontia. METHODS: Records from 200 episodes of repeat DGA were studied
      retrospectively. RESULTS: The mean age of patients at first referral was 5y4m,
      and the mean interval before repeat was 22 months. Self-referrals rose from 14%
      at DGA1 to 30% at DGA2. New caries at second referral, where all diagnosed
      disease had been treated at DGA1, accounted for only 15% of the total. Where a
      specific request was made in the referral, only 8% of letters matched the
      charting made in hospital. 30% of all specific requests were honoured, but then
      required treatment for previously diagnosed caries at DGA2.75% of single-tooth
      extractions required repeat DGA for caries left at DGA1. CONCLUSIONS: It may be
      too optimistic to address only the most grossly diseased teeth when a child
      requires GA exodontia. A more radical treatment-planning approach, combining
      primary care, secondary care and public health considerations, may be required to
      avoid the unnecessary use of DGA.

PMID- 10967823
TI  - The influence of viewing conditions on radiological diagnosis of periapical
      inflammation.
AB  - OBJECTIVES: To determine the effect of viewing conditions upon diagnosis of early
      periapical inflammatory pathosis on intra-oral radiographs, and to examine the
      effect of observer experience upon diagnostic performance in this task. METHODS:
      50 observers examined 18 periapical radiographs using three different viewing
      conditions (room lighting; viewing box; viewing box with x2 magnification and
      masking). Their diagnoses were compared with an 'expert' diagnosis provided by
      repeated viewings of the films by two dental radiologists. Sensitivities and
      specificities were determined. RESULTS: When 'ideal' viewing conditions were
      used, optimal sensitivity (78%) and specificity (78%) were obtained. Use of a
      viewing box was associated with significantly higher specificity than the use of
      room lighting (P = 0.0016). Use of masking and x2 magnification was associated
      with significantly higher sensitivity than a viewing box alone (P = 0.004). There
      were few significant differences in diagnostic performance between observers, but
      qualified dental staff had significantly higher specificities than 4th year (P =
      0.01) and 5th year (P = 0.01) students when a viewing box was used alone.
      CONCLUSIONS: This study on early periapical inflammatory pathosis gives support
      to guidelines which recommend the use of a viewing box, x2 magnification and
      masking for interpreting intra-oral radiographs. It also suggests that observer
      experience may influence interpretation of early periapical pathosis.

PMID- 10967824
TI  - A study of prophylactic antibiotic prescribing in National Health Service general
      dental practice in England.
AB  - OBJECTIVE: To study the use of prophylactic antibiotics by general dental
      practitioners. DESIGN: A postal questionnaire of National Health Service (NHS)
      general dental practitioners in ten English Health Authorities. SUBJECTS: General
      dental practitioners (GDPs) (1544) contracted to provide NHS treatment in the
      Health Authorities of Liverpool, Wirral, Oxfordshire, Buckinghamshire,
      Nottingham, North Nottinghamshire, Sheffield, Newcastle, Northumberland and North
      Tyneside. MAIN OUTCOME MEASURES: The questionnaires were analysed and the
      responses to each question expressed as absolute frequencies. RESULTS: Responses
      to the questionnaires were received from 929 (60.1%) practitioners. Over 40% of
      general dental practitioners would prescribe prophylactic antibiotics for
      patients with no relevant medical history for minor oral surgery to prevent
      postoperative infection. Amoxicillin was the predominant choice of antibiotic in
      this situation. Between 15-67% of GDPs failed to prescribe prophylactic
      antibiotics for at risk medically compromised patients. GDPs also prescribed for
      patients with a medical history not known to be at risk from dental procedures.
      Over 50% of GDPs however, would seek specialist advice about prophylaxis if they
      were unsure of the indications and over 90% of GDPs indicated they would use the
      current recommended regime for antibiotic prophylaxis for patients at risk of
      infective endocarditis. CONCLUSIONS: The evidence from this study suggests that a
      significant number of the practitioners surveyed prescribe prophylactic
      antibiotics inappropriately, both for surgical procedures and for patients at
      risk from endocarditis. There is also evidence that practitioners prescribe
      antibiotic prophylaxis for clinical procedures and medical conditions for which
      there is little evidence. The results suggest that there is a need for the
      development of guidelines for practitioners on the appropriate prophylactic use
      of antibiotics.

PMID- 10967825
TI  - [Solitary cyst of the calcaneus contemporary diagnostic possibilities: the
      results and treatment].
AB  - Bone remodeling within solitary cyst of the calcaneus has been investigated, its
      unique location underlined. Different theories behind its origin within the short
      bone like the calcaneus are discussed. The diagnosis might be supported by
      magnetic resonance imaging according to Greenfield data. At the final
      radiographic assessment according to the Neer criteria in majority of the
      patients incomplete healing with small osteoporotic areas has been found.

PMID- 10967826
TI  - [Intramedullary fixation within bones of the hand: 20 years of experience].
AB  - Intramedullary fixation within bones of the hand has been used for treatment of
      313 fractures in 169 patients after serious trauma or replantation between 1978
      and 1998. Kirschner wires or Steinmann pins were introduced at the fracture site
      and anchored within both metaphyses. The method was used in various types of
      fractures, comminuted ones and bone defects included. In all cases fracture
      healed between 4 and 8 weeks. No deep infection occurred, in 2 patients the
      implants had to be removed because of their migration. The method is technically
      undemanding and allows for immediate postoperative rehabilitation. Total range of
      motion exceeded by 15% results achieved in patients treated with temporary
      immobilization of the hand.

PMID- 10967827
TI  - [An analysis of the selected parameters of the normal hip joint during growth in
      magnetic resonance imaging].
AB  - Dynamics of the selected parameters of the normal hip joint during growth has
      been presented. Fifty-three normal hips in 40 individuals aged 3-17 years were
      assessed with Magneton Impact MRI. The angles and indices were found on T1
      coronal images in Spin Echo or Turbo Spin Echo sequence. Acetabular roof angle of
      Hilgenreiner, acetabular inclination angle of Sharp, Wiberg angle and Heyman
      Herndon index were calculated with both bony and cartilaginous elements regarded.
      Parameters based on cartilaginous parts of the joint did not change during normal
      growth, but they do change if calculated with the use of bony landmarks reaching
      Acartilaginous values by the age of 14-15. The results suggest, that during
      growth gradual ossification of cartilaginous elements takes place but the
      proportions remain unchanged. The investigation determines the age of enhanced
      ossification and the age of its termination.

PMID- 10967828
TI  - [Pedicled osteocutaneous groin flap in the compound reconstruction procedures of
      the fingers].
AB  - The paper presents the authors own experiences with pedicled oseocutaneous groin
      flaps based on superficial circumflex iliac vessels with a vascularized bone
      graft (size ranging from 2.5 cm to 5 cm) from the ilium. Eight patients, 7 males
      and 1 female, (aged 9-46 years, mean age 24 years) were treated using this method
      because a bone defect of the first metacarpal bone or the middle phalanx of the
      III finger. The flap pedicle was cut off after 17-36 days. Treatment was
      successful in all patients, although complications of the healing process were
      noted in 7 flaps. In 5 cases an inflammatory reaction around the sutures or
      superficial necrosis of the skin was observed. In two cases extensive infection
      of the flap's tissues was noted which in one case lead to partial necrosis of the
      soft tissues.

PMID- 10967829
TI  - [Surgical stabilization of fractures and dislocations of the spine].
AB  - Observing the results of surgical treatment in 84 patients (64 males and 20
      females) it was noted that stability of the cervical spine with a damaged
      posterior column could be achieved by using a coticospongious graft wedged in
      between the vertebral bodies. Unstable fractures of the thoracaic, thoracolumbar,
      and lumbar spine are best treated with a transpedicular stabilization system,
      involving application of either rods or plates onto the vertebral bodies. When
      using transpedicular screws, stability is achieved when screws are of the right
      size, are properly implanted into the pedicles and the rods are linked by
      transverse connectors (forming a 3D construction). Reconstruction of the anterior
      column by using bone graft or titanium baskets is of crucial importance.

PMID- 10967830
TI  - [Biomechanical studies of forces occurring in the Ilizarov and Orthofix
      apparatuses during limb lengthening by distractive osteogenesis].
AB  - The magnitude of the distractive forces occurring in the Ilizarov and Orthofix
      apparatuses during limb lengthening by distractive osteogenesis has been
      investigated. Eighteen patients treated between 1995 and 1998 were included in
      the study. The data obtained were computerized and related to clinical,
      radiographic and sonographic findings. Typical and repeatable graphs of forces
      were found during the process of lengthening as well as typical relationships
      between the callus and the values of distractive forces.

PMID- 10967831
TI  - [Total cementless hip replacement complicated by the damage of the femoral
      artery].
AB  - The paper presents the mode of treatment in two patients with injury of the
      femoral artery which resulted during total cementless hip replacement. The first
      patient underwent a total hip replacement procedure because of degenerative
      changes secondary to purulent inflammation during infancy. During the procedure
      the femoral artery was damaged and subsequently sutured. The second patient was
      underwent a total hip replacement procedure because of degenerative changes
      secondary to congenital dislocation of the hip. Two months after implantation of
      a Biocontact prosthesis with a self-threading acetabular component, a false
      aneurysm was diagnosed by ultrasonographic examination. The aneurysm was excised
      and a vascular prosthesis was implanted. This mode of treatment saved both
      patients, while preserving the hip prosthesis. The complication rate was 0.3%.

PMID- 10967832
TI  - [The analysis of causes of divergence between clinical and radiological results
      of conservative treatment for distal radius fracture in patients over 50 years of
      age].
AB  - A series of 231 distal radius fractures treated with closed manipulation and cast
      immobilization has been retrospectively evaluated. Excellent and good results
      were reported in 69.7% (according to patient's evaluation), in 67.1% according to
      Gartland-Werley clinical criteria and in 52.4% according to Sarmiento radiologic
      scale. Fair and poor results constitute circa 30% of results; their share
      increases as the Frykman fracture type increases and so increases the divergence
      between clinical and radiologic results.

PMID- 10967833
TI  - [Influence of patient's age and fracture morphology on the final result of
      conservative treatment].
AB  - Three hundred and thirty-three cases of the distal radius fractures have been
      retrospectively analyzed. The patients were divided into 4 age groups (15-29, 30
      49, 50-69 and above 70 years of age) and into 8 groups according to Frykman's
      classification of fracture morphology. Excellent and good results in the first
      and second age group were found in 84.3% (patients evaluation), in 85.3%
      (clinical evaluation according to Gartland-Werley criteria) and in 87.2%
      (radiologic Sarmiento scale). The scores in age groups III and IV were 69.7%,
      67.1% and 52.4% respectively. Extraarticular fractures (Frykman I and II) were
      found in 69.7% in age groups II and I and in 37.3% in group III and IV. Excellent
      and good results in the extraarticular fractures group were found in 88%
      subjectively, 84.2% clinically and in 85.1% radiologically whilst in the
      intraarticular fractures group in 57.6%, 59.3% and 37.4% respectively. Clinical
      and radiologic results worsen as the fracture morphology gets more complicated
      and this occurs with increasing age of the patient.

PMID- 10967834
TI  - [The use of the garamycin sponge in the treatment of infected pseudoarthrosis of
      the tibia].
AB  - The use of the Garamycin sponge in the treatment of infected pseudoarthrosis of
      the tibia has been presented. The study included 6 male patients aged from 27 to
      56 years; the sponge filled the defect after resection of the pseudoarthrosis.
      The method seems to be the one of choice to support adequate surgical
      intervention grossly contributing to the final positive result.

PMID- 10967835
TI  - [Fatigue tibial fracture coexistent with severe degenerative changes of the knee
      in a patient with rheumatoid arthritis].
AB  - The authors present a case of fatigue fracture of the proximal tibia with
      concurrent degenerative changes of the knee in a 53 year old patient with
      rheumatoid arthritis. The patient was treated surgically with a hinge-rotation
      prothesis. The procedure yielded pain relief, correction of the axis of the lower
      limb with progressive bone union.

PMID- 10967836
TI  - [The Judet and Letournel classification of acetabular fractures].
AB  - Many classifications of acetabular fractures are to be found in literature. The
      fact that various orthopedic centres use different classifications makes an
      objective comparison of methods of treatment and their results difficult, if not
      impossible. The authors of the paper present the principles of the Judet and
      Letrournel classification of acetabular fractures. The Judet and Letournel
      classification is widely accepted and and used by many reknown orthopedic centres
      around the world. Polish literature lacks so far a satisfactory discussion about
      this issue.

PMID- 10967837
TI  - [Treatment of pseudoarthrosis of long bones by surgical stabilization and a
      transfer of in-vitro cultivated bone marrow interstitial cells].
AB  - The paper presents the results of surgical stabilization of pseudoarthrosis of
      long bone augmented by a transfer of in vitro cultivated bone marrow interstitium
      cells in 4 patients. In three cases a Zespol external fixation device was applied
      without opening the pseudoarthrosis. One patient was treated by open reduction of
      the bone fragments with the use of frozen spongiose bone grafts. The mean age of
      the patients was 30.2 years. In two cases the pseudoarthrosis had developed in
      the tibia, in the remaining two cases it developed in the ulna. The
      pseudoarthrosis was present for a mean time of 2.5 years. In all cases healing of
      the pseudoarthrosis was observed after a mean time of 3.7 months.

PMID- 10967838
TI  - [An analysis of selected risk factors of aseptic loosening of hip
      endoprosthesis].
AB  - An analysis of selected risk factors of aseptic loosening of hip endoprosthesis
      has been attempted on the ground of retrospective evaluation of 57 hips in 54
      patients (41 females, 13 males) who underwent revision of the hip replacement.
      Age of the patients at primary surgery ranged from 18 to 73 years (mean 55.6
      years). Follow-up ranged from 8 to 212 months (mean 83 months). Originally, in 45
      cases cemented hip replacement was done and in 12 cementless endoprosthesis was
      implanted. In 34 cases both components were replaced, in 14 cases acetabular
      component, in 9 cases stem only and in 1 case the endoprosthesis was removed.
      Clinical evaluation was done according to Merle-d'Aubignea criteria, radiologic
      assessment was done according to DeLee and Charnley classification and the one of
      Gruen. Within 10 years after primary surgery all cementless hips were revised
      (all Parhofer-Monch type within 5 years). Among Weller cemented replacements both
      components were replaced in 18 cases, acetabulum in 8, the stem in 5 and 1
      endoprosthesis was removed. McKee-Farrar implants were replaced completely in all
      but 2 cases. Most of revisions among cemented hip replacements took place 10
      years after primary operation. Angular migration of the acetabular component was
      found in 40 cases; in 8 cases no migration was observed. Forty-three hips with
      loosened stem have been analyzed: to small size of the stem was found in 6 cases,
      varus deviation was found in 14 cases and valgus deviation in 6. Special
      attention has been paid to the technical errors that are essential for long-term
      result of hip replacement.

PMID- 10967839
TI  - Self-assessment of the competences in occupational medicine as an instrument for
      improving postgraduate training.
AB  - The main goal of the postgraduate training in occupational medicine is to make
      already experienced students develop appropriate competences to deal with health
      problems existing and emerging in the realities of different spheres of
      occupational health. The task requires checking on and evaluation of the
      students' learning process and its results. Thirteen types of competence
      transmitted to the students were made the points of reference in a special self
      assessment questionnaire. The respondents were asked to assess the contribution
      of particular lectures and seminars to the acquirement or improvement of each
      type of competence. The results obtained in a group of students suggest that some
      modifications and improvements in the educational objectives and programmes
      should be introduced.

PMID- 10967840
TI  - Occurrence of pulmonary diseases in steel mill workers.
AB  - The 'Sendzimir' Steel Mill, Cracow, Poland, gives employment to approximately
      17,000 workers. During the years 1994-98, 1396 compensation claims for diseases
      related to occupational hazards were registered. After a scrupulous
      investigation, 851 cases were certified as occupation-related diseases. Of this
      number, 481 cases (56.5%) were diagnosed as pulmonary diseases, including
      silicosis (n = 225, 46.7%); chronic bronchitis (n = 138, 28.7%); lung carcinoma
      (n = 59, 12.3%); epithelial cancer (n = 42); adenocarcinoma (n = 12);
      microcellular carcinoma (n = 5); asthma, 12 atopic and 24 non-atopic (n = 36,
      7.5%); and asbestosis (n = 23, 4.8%). Chronic bronchitis was diagnosed in
      patients exposed to industrial dusts, containing SiO2, NOx, and SO2. Asthma
      occurred most frequently among those exposed mainly to Cr+6, Co and Ni containing
      dusts, and lung carcinoma in those exposed to policyclic aromatic hydrocarbons,
      including benz(a)pyren, asbestos, chromium, vapours of oils and lubricants. In
      1994-96, chronic bronchitis and silicosis, and in 1997-98, lung carcinoma and
      asthma were most frequently diagnosed in the workers under study. It is likely
      that the diminishing frequency of chronic bronchitis and silicosis was the
      consequence of technological progress, and greater concern for hygiene standards.
      Increasing incidence of lung cancer reflects long latency characteristic of this
      illness.

PMID- 10967841
TI  - Air pollution and acute respiratory diseases in children: regression analysis of
      morbidity data.
AB  - The aim of this study was to investigate the relationship between acute
      respiratory diseases and the air quality in the urban area of the Upper Silesian
      Industrial Zone during autumn and winter with special emphasis on temporal
      variability in the air concentrations of pollutants. The survey was carried out
      in 5 primary care units in Chorzow where the morbidity data on the selected
      respiratory diseases were collected from 1 November 1992 to 31 March 1993. The
      air pollution data were obtained from the monitoring station, being a part of the
      Sanitary and Epidemiological Station Network. Regression analysis with mean
      values of concentrations of air pollutants as explanatory variables revealed a
      positive effect of combined suspended particulate matter and SO2 concentration on
      the increased prevalence of bronchitis and bronchiolitis. Similar and even
      stronger effect was observed at the level of temporal variability coefficients of
      the air pollutants. A hypothesis that temporal variability of the air
      concentration of pollutants might be a more relevant factor for determining the
      prevalence of respiratory diseases than simple mean values of the pollutant
      concentrations is very interesting worthy of further investigations.

PMID- 10967842
TI  - Mortality of workers at two asbestos-cement plants in Poland.
AB  - To assess mortality rate among workers occupationally exposed to asbestos, cohort
      studies were carried out in two asbestos cement plants operating since the 1960s.
      Asbestos cement sheets for roofing and siding have been manufactured there, using
      mostly chrisotile, and since 1985 also crocidolite for pressure pipes. In all,
      the cohort comprised 3,220 workers, including 2,616 male workers. Subject to
      consideration were the workers employed for at least three months in the period
      between the onset of the production and 1980. The vital status of the subjects
      was traced up to 31 December 1991. The availability of the cohort was 96.8%.
      Workers' mortality was analysed using standardized mortality ratio (SMR). The
      reference group was the general population of Poland. In the male cohort, 385
      cases of death were recorded. Statistically significant excess of mortality from
      large intestine cancer (7 cases, SMR = 264) and pleural mesothelioma (5 cases,
      SMR = 2846) was found. In male workers who died from pleural mesothelioma the
      work history ranged from 12 to 26 years. An excess mortality from pleural
      mesothelioma was also noted among the female workers (2 cases, SMR = 11,275). No
      malignant neoplasms of other locations produced significant excess mortality
      either in the male or female workers.

PMID- 10967843
TI  - Mobilization of mercury by DMPS in occupationally exposed workers and in model
      experiments on rats: evaluation of body burden.
AB  - The aim of the study was to evaluate the efficacy of DMPS (sodium-2,3-dimercapto
      1-propane sulfonate) (Dimaval) administration for mobilizing mercury from the
      body in occupationally exposed people and experimental animals. Two doses of DMPS
      were administered at a 24-h interval to: (a) groups of people occupationally
      exposed to merkury--workers of the chloralkali industry (n = 43), and dentists (n
      = 12), (b) non-exposed individuals (n = 20), and (c) rats chronically exposed to
      mercury vapour at the concentration of 0.8 mg/m3 Hg degree (6 h/day, 5 days/week)
      for 15 weeks. In an out-patient mobilizing test, the urinary excretion of mercury
      48 h after the administration of the first dose reached 1513 micrograms in the
      group of industrial workers, 132.6 micrograms in dentists, and 3.78 micrograms in
      controls. In rats, two consecutive doses of DMPS decreased kidney content of
      mercury by about 30% and 50% after oral and intraperitoneal administration,
      respectively. Kidney mercury burden was calculated on the basis of the data from
      animal and human studies of the mobilization of mercury via urine after DMPS
      treatment: 61, 2800 and 28,000 ng/g in controls, dentists and workers,
      respectively. It was estimated that two doses of DMPS mobilized 17-20% (after
      oral administration) and 25-30% (after intramuscular administration) of kidney
      mercury burden, both in the control and exposed subjects.

PMID- 10967844
TI  - Temperature calibration of Pico-Rad detectors for radon measurement.
AB  - A simple mathematical equation linking the activity of adsorbed radon in the
      vials to the time and temperature of its exposure is discussed. The calibration
      coefficient--Ks, defined as activity measured in cpm after saturation time,
      corresponding to radon air concentration of 1 Bq m-3, was determined for four
      temperatures: 284, 291, 294 and 298 K. A linear relationship of ln Ks values
      versus T-1 was found. The relatively high difference in Ks values: 2.12 and 1.24
      cpm/Bq m-3 for the temperatures of 284 and 298 K, respectively, was observed. It
      indicates that temperature fluctuations during Pico-Rad vial exposure may lead to
      erroneous results if the constant average temperature of exposure is introduced
      into a commonly used computer programme for calculating Rn concentration.

PMID- 10967845
TI  - Sub-chronic inhalation toxicity of 1,2,4-trimethylbenzene (pseudocumene) in rats.
AB  - Toxic effects of exposure of 1,2,4-trimethylbenzene (pseudocumene) in the
      condition of sub-chronic inhalation experiment were examined. Rats were exposed
      to vapours of pseudocumene at concentrations of 123 mg/m3, 492 mg/m3 and 1230
      mg/m3, 6 h/day, 5 days/week for 3 months. After 3 months of inhalation exposure
      animals were necropsied. Blood samples were obtained and selected organs were
      weighted and prepared for histological examinations. Sub-chronic inhalation
      exposure to pseudocumene resulted in an overall low degree of systemic toxicity.
      There were no changes in body weight gain, food consumption and absolute and
      relative organ weights. Slightly higher activity of sorbitol dehydrogenase was
      observed in male rats exposed to all concentrations applied. Some disturbances in
      hematological parameters characterised by decrease in red and increase in white
      blood cells were observed in male rats exposed to high concentration of 1230
      mg/m3. The pulmonary lesions observed in male and female rats were statistically
      significant at mid and high concentrations of pseudocumene.

PMID- 10967846
TI  - Circadian variations in hepatotoxicity of carbon tetrachloride in mice.
AB  - Male mice of Balb/C strain were administered i.p. carbon tetrachloride, in single
      doses of 35 and 145 mg/kg, given at variable time of the day. The activity of
      alanine aminotransferase (ALAT) in serum, and the hepatic level of
      malondialdehyde (MDA) as well as reduced glutathione (GSH) were adopted as
      indicators of toxicity. In selected groups, liver histopathology was carried out.
      The experiment was performed in two series differing in the dynamics of
      observations. A differentiation of the intensity of toxic effects was found
      dependent on the time of the day at which animals were administered the
      xenobiotic. This was especially evident for a lower dose: given in the morning it
      produced no effects, whereas given in the evening it resulted in distinct
      elevation of toxicity indicators. Additionally, the correlation was checked
      between the histopathological evaluation (semiquantitative expression) and serum
      ALAT activity. A high correlation (r = 0.98) allows for basing the evaluation of
      liver necrosis on the ALAT activity alone.

PMID- 10967847
TI  - Informed consent.

PMID- 10967848
TI  - Euthanasia and assisted suicide.

PMID- 10967849
TI  - Research and development in Irish primary care.
AB  - Primary care is central to the health system and patient care. Evidence for the
      optimal delivery of such healthcare can only be obtained by research and
      development involving primary care practitioners and their patients. The present
      capacity of Irish primary care to provide this evidence base is limited. A
      coherent strategy to improve the quantity and quality of Irish primary care R&D
      is outlined. Consideration is given to how research findings will be implemented.

PMID- 10967850
TI  - Drug reimbursement in Ireland.

PMID- 10967851
TI  - Hyperprolactinaemia: analysis of presentation, diagnosis and treatment in the
      endocrine service of a general hospital.
AB  - The charts of 184 patients with clinically significant hyperprolactinaemia who
      presented to a teaching hospital between 1978-1995 were reviewed, 158 (86%)
      females and 26 (14%) males. Hyperprolactinaemia was due to a microadenoma or was
      idiopathic in 36.4%, drug induced in 16%, associated with a macroadenoma in 12%,
      due to epilepsy in 7%, with other causes each contributing 5% or less. The
      presenting symptoms were amenorrhoea in 64%, galactorrhoea in 40.5%, infertility
      in 15%, visual field defect in 9%, with impotence in 30% and, gynaecomastia in 8%
      of men. One hundred and one patients were treated with bromocriptine (80%),
      surgery (35.4%) and radiotherapy (10.7%). Twenty-five percent of patients
      developed side-effects of bromocriptine for which cabergoline, a new long-lasting
      dopaminergic agonist, was successfully substituted. Presenting features responded
      to drug treatment in 70-80% of patients.

PMID- 10967853
TI  - The beneficial role of transvaginal ultrasound in the preoperative
      characterisation of dermoid cysts of the ovary.
AB  - The advent of transvaginal sonography has improved the ability of radiologists to
      visualise both ovaries and has facilitated the preoperative characterisation of
      many of these lesions. We describe the beneficial role of transvaginal sonography
      in the accurate preoperative characterisation of dermoid cysts of the ovary in
      two patients and describe the characteristic features of ovarian dermoid cysts.

PMID- 10967852
TI  - Delays in administration of acetylcysteine in paracetamol overdose.
AB  - Despite an effective antidote, paracetamol overdose is a frequent cause of
      fulminant hepatic failure in Ireland and the United Kingdom. Most treatment
      failures are due to late presentation but some may be related to delayed
      treatment in hospital. The aim of this study was to investigate delays in
      treatment in patients presenting to two large Dublin accident and emergency
      departments. One hundred and seventy seven admissions were recorded over a two
      year period. The average patient presented 6-8 hours after the overdose and
      waited another 1.5 to 2 hours for treatment to commence. Treatment was delayed
      more than 2 hours after presentation in 24/110 (22%) and more than 4 hours in
      10/110 (10%). The majority had no adverse sequelae but four patients required
      ventilation, one haemofiltration and one died. The patient who died presented 35
      hours after overdose. This study suggests that delays in treatment of paracetamol
      overdose are common. Delays of this magnitude may be clinically important in the
      small minority of patients with significant liver injury. It is possible that
      oral administration of n-acetylcysteine may reduce delays in treatment.

PMID- 10967854
TI  - A novel presentation of cryptococcal infection in a renal allograft recipient.
AB  - The population of immunosuppressed patients is growing rapidly because of the HIV
      epidemic and the rapid expansion in transplant medicine. These patients may
      present to a variety of clinical specialties with seemingly innocuous infections.
      We present here the first Irish case of primary cryptococcal cellulitis. The
      patient was a 62-year old renal transplant recipient and was immunosuppressed
      with Cyclosporine, Azathioprine and Prednisolone. He presented with an apparent
      bacterial cellulitis on the dorsum of the hand that had failed to respond to a 3
      week course of oral antibiotics. There was no clinical evidence of systemic
      infection. There was tissue necrosis present and the area was debrided
      surgically. Histological examination of debrided tissue revealed necrotic
      granulomata and budding yeast-like organisms. Cryptococcus neoformans was
      cultured from this specimen. The patient was treated with oral fluconazole 400 mg
      daily for 6 weeks with complete healing of the infected area and no evidence of
      recurrence after 12 months of follow up. This case emphasises the need for a high
      index of suspicion for atypical infection in the immunocompromised patient.

PMID- 10967855
TI  - An acute stroke service: potential to improve patient outcome without increasing
      length of stay.
AB  - Acute stroke is associated with a high morbidity and mortality: up to 24% of
      patients may not survive their hospital admission. Stroke unit care has been
      shown in a meta-analysis to reduce this morbidity and mortality. We present a
      three-year audit of the first acute stroke service in an Irish teaching hospital.
      The audit was carried out prospectively on 193 patients admitted to the acute
      stroke service, from July 1996 to end of June 1999. Details regarding patients,
      type and severity of stroke, length of stay and outcome were collected
      prospectively on a standard pro-forma. We observed a reduction in mortality from
      19% to 15% to 9%, and an increasing percentage of patients discharged home from
      55% to 64% to 68%, in year 1, year 2 and year 3 respectively. A trend towards a
      greater number of patients, younger age and improved outcome with lower mortality
      was observed from year to year, without significant change in length of stay.
      This study confirms the value to patients of organised stroke care in terms of
      reduction in mortality and morbidity without increasing length of stay or
      disability. We suggest that every acute hospital should have organised stroke
      care.

PMID- 10967856
TI  - Abdominal cervical cerclage case report.

PMID- 10967857
TI  - Rectus sheath haematoma: an unusual diagnosis.
AB  - Rectus sheath haematoma is a very rare occurrence. There were four cases in this
      hospital within a three month period. In this article, these cases, their
      investigation and management arc reported. A review of the literature was
      undertaken to ascertain how best to diagnose and treat this condition.

PMID- 10967858
TI  - Biochemical ratios as indicators of health, ageing and disease.

PMID- 10967859
TI  - An end to managed care: a vote of confidence in doctors.

PMID- 10967860
TI  - The contribution of medical biochemistry to new technologies in medicine.

PMID- 10967861
TI  - Non-ionizing electromagnetic radiation and public health.

PMID- 10967862
TI  - Medical treatment of hepatorenal syndrome.

PMID- 10967863
TI  - Drug treatment for Alzheimer's disease.

PMID- 10967864
TI  - What do Irish women know about cervical screening?
AB  - In anticipation of the launch of the national cervical screening programme, a
      questionnaire was distributed amongst 200 women on the maternity wards of the
      Coombe Women's Hospital. The questionnaires revealed that 24% of the women
      surveyed never had a smear test and 50% of these did not know how the test was
      performed. The majority of all women did not know what a smear test showed and
      26% did not know the meaning of an abnormal smear. Irish women's knowledge of
      cervical screening is limited, and the success of the proposed programme will
      depend on an improvement in public information and education.

PMID- 10967865
TI  - Pharmacoeconomics of lipid lowering therapy in Ireland.
AB  - Increases in expenditure on medicines above the level of increases in health care
      are generally, a feature of all Western health systems. From the early 1990's,
      the average annual growth rate (AAGR) in pharmaceutical expenditure exceeded the
      AAGR in health among all the European member states 1. In Ireland, the
      expenditure on drugs, as a percentage of health care spending, was 7.1% in 1987
      compared with 9.2% in 1997. The state expenditure on medicines increased from
      165.8 million Pounds in 1993 to 278 million Pounds in 1998 representing an
      average increase of 11% each year. All the available evidence indicates that the
      expenditure on medicines will continue to show real growth, and take an
      increasing share of the total health care budget. Analysis shows that the main
      reasons driving such growth include those of "product mix"--the prescribing of
      newer, more expensive medicines, in addition to the 'volume effect' comprising
      growth in the number of tablets per prescription. These two factors account for
      80% of the observed increase in drug cost 2. Six therapeutic classes accounted
      for 16 of the top 20 most expensive drugs prescribed under the GMS in 1998 3.
      These areas can be classified as follows: peptic ulcer disease, asthma,
      hypertension/cardiac failure, antidepressants, anti inflammatory and lipid
      lowering drugs. In this article we discuss the clinical evidence base, and the
      pharmacoeconomic implications of lipid lowering therapy in this country.

PMID- 10967867
TI  - Delusions of infestation--a case report of response to risperidone.

PMID- 10967866
TI  - Latex allergy--implications for Irish patients and healthcare workers.
AB  - A 34-year-old lady presented with an exacerbation of her atopic dermatitis. She
      also gave a history of angioedema during labour. Type I latex hypersensitivity
      was confirmed by serological and epicutaneous testing. Virtually unrecognised
      until the 1980s, latex hypersensitivity is now being reported more and more
      frequently, particularly in spina bifida patients, atopics and healthcare
      personnel. The importance of this problem for patients and healthcare personnel
      is discussed.

PMID- 10967868
TI  - A case study of non-binding mediation in practice: Rush-Presbyterian-St. Luke's
      Medical Centre, Chicago, medical malpractice mediation programme.

PMID- 10967869
TI  - Incidental diagnosis of breast carcinoma following technetium 99m tetrofosmin
      (myoview) scintigraphy for evaluation of ischaemic heart disease.

PMID- 10967870
TI  - Increased incidence in childhood empyema thoracis in Northern Ireland.

PMID- 10967871
TI  - Non-specialist paediatric surgery--where should it be performed?

PMID- 10967872
TI  - Editorial commentary regarding prevention of blood borne diseases in the health
      care setting (Sep/Oct '99).

PMID- 10967873
TI  - Restless leg syndrome--mechanical and cramps (Aug '99).

PMID- 10967874
TI  - The Barker hypothesis (Sep/Oct '99).

PMID- 10967875
TI  - Baring the sole. The rise and fall of the shoe-fitting fluoroscope.
AB  - One of the most conspicuous nonmedical uses of the x-ray was the shoe-fitting
      fluoroscope. It allowed visualization of the bones and soft tissues of the foot
      inside a shoe, purportedly increasing the accuracy of shoe fitting and thereby
      enhancing sales. From the mid 1920s to the 1950s, shoe-fitting fluoroscopes were
      a prominent feature of shoe stores in North America and Europe. Despite the
      widespread distribution and popularity of these machines, few have studied their
      history. In this essay we trace the origin, technology, applications, and
      significance of the shoe-fitting fluoroscope in Britain, Canada, and the United
      States. Our sources include medical and industrial literature, oral and written
      testimony of shoe retailers, newspapers, magazines, and government reports on the
      uses and dangers of these machines. The public response to shoe-fitting
      fluoroscopes changed from initial enthusiasm and trust to suspicion and fear, in
      conjunction with shifting cultural attitudes to radiation technologies.

PMID- 10967876
TI  - B. B. Warfield (1851-1921). A biblical inerrantist as evolutionist.
AB  - The theological doctrine of biblical inerrancy is the intellectual basis for
      modern creation science. Yet Benjamin Breckinridge Warfield of Princeton
      Theological Seminary, the theologian who more than any other defined modern
      biblical inerrancy, was throughout his life open to the possibility of evolution
      and at some points an advocate of the theory. Throughout a long career Warfield
      published a number of major papers on these subjects, including studies of
      Darwin's religious life, on the theological importance of the age of humanity
      (none) and the unity of the human species (much), and on Calvin's understanding
      of creation as proto-evolutionary. He also was an engaged reviewer of many of his
      era's important books by scientists, theologians, and historians who wrote on
      scientific research in relation to traditional Christianity. Exploration of
      Warfield's writing on science generally and evolution in particular retrieves for
      historical consideration an important defender of mediating positions in the
      supposed war between science and religion.

PMID- 10967877
TI  - Resiliency and prevention in college health.

PMID- 10967878
TI  - Predictors of vaccination rates during a mass meningococcal vaccination program
      on a college campus.
AB  - Factors contributing to students' compliance with mass vaccination programs
      during meningococcal outbreaks have not been well described. A 1997 mass
      vaccination campaign at Michigan State University provided an opportunity to
      study such factors. Of 34,024 students in the target population, 17,538 (51.5%)
      were vaccinated in 5 days. Vaccination rates were higher for women (47.9%) than
      for men (43.1%) and higher for on-campus residents (65.3%) than for off-campus
      residents (35.6%). For each year of students' age beyond 19, the adjusted odds of
      vaccination were reduced by 0.82. Adjusted odds ratios for vaccination, with
      White students as the reference group at 1.0, were 1.33 for Asian American
      students, 0.97 (not significant) for Hispanic students, 0.82 for African American
      students, and 0.80 for Native American students. Students from the Colleges of
      Business, Engineering, Communication, and Natural Science had the highest
      vaccination rates; those from the College of Arts and Letters had the lowest
      rates.

PMID- 10967879
TI  - Prevalence of psychological symptoms among undergraduate students in an
      ethnically diverse urban public college.
AB  - The levels of psychological symptoms (anger, anxiety, and depression) among 595
      college students in an ethnically diverse urban public college were surveyed. The
      students reported a wide range of symptoms that were quite similar to those
      reported by a representative sample of adults in the United States in the 1990s.
      Among these Asian, Black/African American, Latino/Hispanic, White, and other
      ethnic minority students, women's levels of symptoms were higher than men's
      (although the differences were small). Older students reported lower levels of
      anger and depression (the differences were even smaller), and ethnic groups did
      not differ in manifestations of psychological symptoms. Some of these students,
      however, reported problematic levels of psychological symptoms that were similar
      to those reported by more traditional college and university students.

PMID- 10967880
TI  - Factors influencing condom use and STD acquisition among African American college
      women.
AB  - To identify factors that influence condom use and the risk of acquiring sexually
      transmitted diseases (STDs) among African American college women, the authors
      surveyed a sample of 123 sexually experienced undergraduate women at a state
      university. The college women who were older, had initiated sex earlier, or had
      more recent sexual partners were more likely than others in the study to report a
      history of an STD. The findings have implications for prevention and intervention
      programs for African American college women.

PMID- 10967882
TI  - A personal diary of the outsourcing of a university student health service.

PMID- 10967881
TI  - Men, masculinity, and cancer: risk-factor behaviors, early detection, and
      psychosocial adaptation.
AB  - Men and women experience cancer differently. More men than women get cancer, more
      men than women die from cancer, and men usually adapt less well than women after
      a cancer diagnosis. In this article, the author suggests that the consequences of
      male gender-role socialization may explain some of these differences. The focus
      of the article is on (a) cancer risk-factor behaviors; (b) screening, early
      detection, symptom recognition, and help seeking; and (c) psychosocial
      adaptation. Research that has identified gender differences is reviewed and the
      impact of male gender-role socialization is offered as a potential explanation
      for these differences. In addition, practice implications for college health
      professionals are offered.

PMID- 10967883
TI  - Should college health providers use e-mail to communicate with their patients?
      Two points of view.

PMID- 10967884
TI  - Advance medical directives for college students: it's not your father's living
      will.

PMID- 10967885
TI  - College students and the diagnosis of attention deficit hyperactivity disorder.

PMID- 10967886
TI  - Early lexical development in English- and Korean-speaking children: language
      general and language-specific patterns.
AB  - The present study examined the composition of the early productive vocabulary of
      eight Korean- and eight English-learning children and the morpho-syntactic,
      semantic, and pragmatic characteristics of their caregivers' input in order to
      determine parallels between caregiver input and early lexical development.
      Vocabulary acquisition was followed using maternal diary and checklists for the
      Korean-learning children (from a mean age of 1;6 to 1;9) and for the English
      learning children (from a mean age of 1;4 to 1;8). Results showed that both
      Korean-learning and English-learning children acquired significantly more nouns
      than verbs at the 50-word mark. However, Korean children learned significantly
      more verbs than did English-learning children. The relative ease with which
      Korean learners, as compared to English learners, acquired verbs parallels
      several differences in the linguistic and socio-pragmatic characteristics of the
      input addressed to them. Korean-speaking caregivers presented more activity
      oriented utterances, more verbs, and more salient cues to verbs than did English
      speaking caregivers. These data suggest that both general and language-specific
      factors shape the early lexicon.

PMID- 10967887
TI  - Predictive validity of the New Zealand MacArthur Communicative Development
      Inventory: Words and Sentences.
AB  - This study assessed the long-term predictive validity of the MacArthur
      Communicative Development Inventories: Words and Sentences (CDI:WS; Fenson, Dale,
      Reznick, Thal, Bates, Hartung, Pethick & Reilly, 1993) for children's expressive
      and receptive vocabulary development. Sixty-one New Zealand children (31 females)
      were assessed with a New Zealand version of the CDI: WS at 1;7 and 2;1 and with
      the Expressive Vocabulary Test (Williams, 1997) and the Peabody Picture
      Vocabulary Test-III (Dunn & Dunn, 1997) at 2;8 and 3;4. Excellent reliability and
      good predictive validity was obtained for the NZ CDI:WS even over a 21-month
      delay. Predictive validity of the NZ CDI:WS for the PPVT-III was higher for
      children of mothers with less education. We discuss the implications of these
      results for use of the CDI:WS with children from a broad range of cultural and
      educational backgrounds.

PMID- 10967888
TI  - How children build their morphosyntax: the case of French.
AB  - Early morphosyntax is very rich and uniform in young French-speaking children.
      The present study aims to give a thorough analysis of the morphosyntax produced
      at the outset of multi-word speech, with a classification of free language
      produced at 2;0 by 27 French-speaking children. The corpus was fully tagged by an
      automatic part-of-speech tagger. A classification performed with words taken in
      isolation shows a clear difference between the categories used in single-word
      utterances and those used in multi-word utterances. A classification performed
      with word sequences reveals surprisingly adult-like sequences of syntactic
      categories and words; the non-adult combinations are few in a French child's
      language. The very successful use of the tagger demonstrates the morphosyntactic
      coherence of the child's speech. When compared with adult language, the
      quantitative results, and more precisely the data concerning regularity and error
      types, contribute to the documentation of all the specificities of the emerging
      morphosyntax in normally developing French children.

PMID- 10967889
TI  - Vocabulary growth in late talkers: lexical development from 2;0 to 3;0.
AB  - Vocabulary growth from 2;0 to 3;0 was studied in 28 late talkers using expressive
      vocabulary inventories reported bimonthly on the Language Development Survey
      (LDS). Group milestones were 18 words at 2;0, 89 words at 2;6, and 195 words at
      3;0. A sub-group of 11 children (Group 1) showed a rapid vocabulary spurt between
      2;2 and 2;8, reached the 150-180 word mark by 2;6, and attained the LDS ceiling
      of about 300 words by 2;10. In contrast, the 17 children in Group 2 still had a
      mean vocabulary of fewer than 30 words at 2;6, had less of a vocabulary spurt
      when they did start acquiring words, and attained the 150-180 vocabulary mark at
      3;0. All 3;0 language outcome measures were significantly predicted by LDS
      vocabulary size from 2;2 to 2;4.

PMID- 10967890
TI  - Comprehension and production of relative clauses: a comparison between Swedish
      impaired and unimpaired children.
AB  - The aim of the present study is to investigate the relationship between language
      comprehension and language production in Swedish children. This was done
      longitudinally with 10 children with specific language impairment (SLI), aged 4;0
      to 6;3 at Time I, and 10 children with unimpaired language development, aged 3;1
      to 3;7 at Time I. The target structure was subordination, more precisely relative
      clauses. The children's comprehension was tested with picture pointing, act-out
      and oral response tests. Their production was tested with elicited imitation and
      sentence completion tests. Data were collected twice, with an interval of six
      months. The results from the unimpaired children at Time I showed a difference
      between comprehension and production. At Time II these children scored higher on
      production than on comprehension. The children with SLI scored significantly
      higher on comprehension than on production at Time I. In half of the SLI group
      there was a clear development between the two data collection sessions,
      diminishing the dissociation. On neither testing did the children with SLI differ
      significantly from the unimpaired children in comprehension. At both testings,
      however, the children with SLI had significantly more responses where they did
      not insert the complementizer in relative clauses. The results indicate that the
      relationship between comprehension and production is different at different
      stages in development. They also show that structures involving dependency
      relations are particularly difficult to produce for children with SLI.

PMID- 10967891
TI  - Phonological priming in children's picture naming.
AB  - Two experiments examined phonological priming in children and adults, using a
      cross-modal picture-word interference task. Pictures of familiar objects were
      presented on a computer screen, while interfering words (IWs) were presented over
      headphones. In terms of their relation to target pictures, IWs were either
      phonologically related, unrelated, neutral (the word go), or identical. Ninety
      children (30 aged 4;11 to 5;11, 30 aged 6;11 to 7;11, and 30 aged 9;5 to 11;9)
      and 30 adults were instructed to name the pictures as quickly as possible while
      ignoring the IWs. In Experiment 1, related IWs shared onset consonants with the
      names of the pictures. Across ages, participants named pictures faster with
      related IWs than with unrelated IWs. In Experiment 2, related IWs rhymed with the
      targets. Here, only the youngest children (five to seven-year-olds) named
      pictures faster with related IWs than with unrelated IWs. The results indicate
      that priming effects reach a peak during a time when articulatory information is
      being consolidated in the output phonological buffer. The disappearance of the
      rhyme priming effect with age may reflect the gradual emergence of the onset as
      an organizing structure in speech production. This increased prominence of the
      onset can be viewed as one component of a just-in-time, incrementalist approach
      to speech production that allows adults to speak more fluently than children.

PMID- 10967892
TI  - Children's understanding of homonymy: metalinguistic awareness and false belief.
AB  - The aim of this study was to explain why children have difficulty with homonymy.
      Two experiments were conducted with forty-eight children (Experiment 1) and
      twenty-four children (Experiment 2). Three- and four-year-old children had to
      either select or judge another person's selection of a different object with the
      same name, avoiding identical objects and misnomers. Older children were
      successful, but despite possessing the necessary vocabulary, younger children
      failed these tasks. Understanding of homonymy was strongly and significantly
      associated to understanding of synonymy, and more importantly, understanding of
      false belief, even when verbal mental age, chronological age, and control
      measures were partialled out. This indicates that children's ability to
      understand homonymy results from their ability to make a distinction
      characteristic of representation, a distinction fundamental to both
      metalinguistic awareness and theory of mind.

PMID- 10967893
TI  - Mothers' ability to identify infants' communicative acts consistently.
AB  - A mother's ability to identify consistently what she perceives to be
      communicatively salient behaviours is considered to be fundamental to the process
      of responding sensitively to prelinguistic infants. The present study
      investigated the ability of 35 mothers to identify consistently what they
      perceived to be communicative acts by infants at three ages (0;6, 0;9, and 1;0).
      Each mother coded the same videotape of her infant's behaviour on two occasions,
      three months apart, and observed measures of agreement (consistency) between
      coded records were obtained. A randomization procedure was used to provide
      distributions of chance levels of agreement between coded records with which
      observed measures were compared. Comparisons of the mothers' coded records
      indicated that they were able to identify infants' communicative acts
      consistently at each age.

PMID- 10967894
TI  - Child language with mother and with stranger at home and in the laboratory: a
      methodological study.
AB  - This methodological study in 33 two-year-olds shows that child speech (total
      utterances, word roots, MLU) occurs at about the same level in different settings
      (the familiar home vs. the unfamiliar laboratory), but that children speak more
      and in more differentiated ways with different people (mother vs. stranger).
      Child speech also shows significant short-term stability. Girls use more
      different word roots and speak in longer utterances than do boys. In spontaneous
      child speech, cross-context generalizations appear warranted, but they also
      depend on conversational partner and gender of child.

PMID- 10967895
TI  - Temporal reference in Chinese mother-child conversation: morphosyntactic,
      semantic and discourse-pragmatic resources.
AB  - This paper explores two Mandarin-speaking children's (3;2 and 3;3) ability to
      refer to the past in mother-child conversation. The approach encompasses
      morphosyntactic, semantic and discourse-pragmatic perspectives. The results show
      that the children tend to refer to immediate past spontaneously, but rely heavily
      on elicitation when referring to earlier past. It is suggested that maternal
      scaffolding functions as a discourse support for children to participate in
      conversation involving earlier past. When establishing past reference with overt
      temporal markers, the children resort mainly to aspect markers. In addition, they
      also rely on semantic and discourse-pragmatic resources for temporal inferencing,
      such as inherent semantic aspect, shared background knowledge and situational
      context.

PMID- 10967897
TI  - [Compliance to treatment recommendations in patients with obstructive sleep apnea
      at least one year after diagnosis].
AB  - 102 OSA patients, qualified for nCPAP treatment at least one year ago were
      investigated by questionnaire and direct examination. CPAP device has been used
      by 76 patients (75%). Other subjects (26 persons) did not use it for various
      reasons. Subjects treated (Group L) and not treated (Group NL) were compared.
      Before qualifying for nCPAP treatment, Group L compared to Group NL, had
      significantly higher apnoea/hyponoea index, AHI (p < 0.001) and more severe
      hypoxaemia during sleep (p < 0.01). Subjects of Group L were more obese (p <
      0.01) and smoked more cigarettes per day (p < 0.05) than Group NL. Group L
      patients have been using nCPAP for 6.3 +/- 0.2 nights per week and 6.4 +/- 0.2
      hours per night. From variables characterizing OSA and obesity, the intensity of
      nCPAP usage positively correlated with AHI (p < 0.05) and negatively with
      severity of daytime sleepiness (p < 0.001). Among Group L patients, 93% reported
      general improvement, 84% woke up refreshed and rested in the morning and 70% did
      not feel sleepy during the daytime. Concentration improved in 66% of treated
      patients. Main complaints were associated with rhinitis (38%), uncomfortable mask
      (34%) or air leaks around the mask (26%), dryness in throat and nose (33%),
      shallow, unquiet sleep with frequent awakenings (about 31%), chest pain (23%) or
      headache (22%). 33% of subjects complained of machine noise, troubling sleep
      partner. CONCLUSIONS: The acceptance of nCPAP treatment was 75% and depended on
      the OSA severity. nCPAP device was effective in OSA treatment, mild side effects
      were reported by around one third of studied patients.

PMID- 10967896
TI  - [Assessment of antibiotic treatment effectiveness for prophylaxis of
      postoperative wound infections].
AB  - Uniform prevention of postoperative infections has been introduced in the second
      half of 1998. Patients who underwent lung tissue resection were treated with the
      2nd generation cephalosporin on the day of operation and every 8 hours within
      next 24 hours. Patients operated on trachea and oesophagus additionally received
      metronidazol. Those prevention methods were applied to 465 patients. Infections
      of postoperative wounds were observed only in 1.1% of patients, compared to 3.8%
      of patients in whom such infections were found before the beginning of the
      prophylactic regime.

PMID- 10967898
TI  - [Evaluation of surgical treatment results for pneumothorax in patients from the
      Institute of Tuberculosis and Chest Diseases].
AB  - 2421 patients with pneumothorax (491 women and 1930 men), at the mean age of 42
      years were treated in the Institute of TB and Lung Diseases in years 1975-1997.
      There were 2209 cases with primary pneumothorax and 739 (33%) cases with
      recurrent pneumothorax. Among these 739 patients, only 439 patients were treated
      previously in the Institute of TB and Lung Diseases because of the primary
      pneumothorax. Percentage of the "own recurrences" was 16.7%. Only 34% of patients
      were admitted to the hospital before the elapse of 12 hours after the appearance
      of symptoms; the next 11% of patients--before 24 hours. The rest of the patients
      were hospitalised later than the above mentioned time, even 7 days after the
      first symptoms. A mean duration of hospitalisation of patients with primary
      pneumothorax was 12 days, with the recurrent pneumothorax--13.6 days. In 1/3 of
      patients pneumothorax was related to exertion. Chest X-ray showed partial
      pneumothorax in 3/4 of patients, total pneumothorax--in 1/4 of patients. The
      general condition of 1/3 of patients was assessed as medium-heavy and heavy. In
      703 cases (29%) coexistence of emphysema bullosa was found, in 524 cases (22%)--a
      past tuberculosis lesions, in 42 cases--neoplasm, in 589 cases (20%)-
      inflammation of the respiratory system. Conservative management was applied in
      211 patients (7%). It was satisfactory in 94% of cases. The intercostal tube
      drainage was performed in 2583 patients (88%). The duration of drainage lasted
      from 2 to 551 days (x = 6.6 (4.9 days). The results of treatment were
      satisfactory in 76% of cases, without any complications. In 331 patients the most
      important complication was the leakage of air lasting longer than 7 days. In 167
      patients the result of treatment was unsatisfactory. Thoracotomy was performed on
      152 patients. Twelve patients (0.46%) died.

PMID- 10967899
TI  - [Effect of nocturnal hypoxia on pulmonary hemodynamics in patients with
      obstructive sleep apnea].
AB  - Effects of apnoea induced nocturnal hypoxia on pulmonary haemodynamics (PH) in
      pts with OSA are still under debate. We studied PH in 67 pts (64 M and 3 F) mean
      +/- SD: age 45 +/- 8 years, with severe OSA, AHI 62 +/- 22. Patients had normal
      spirometry: FVC 98 +/- 15% N, FEV1 97 +/- 16% N and arterial blood gases--PaO2 72
      +/- 10 mmHg, PaCO2 40 +/- 4 mmHg. PH were studied using Swan-Ganz thermodilution
      catheter. PH were within normal range: right atrial pressure 4.2 +/- 2.7 mmHg,
      right ventricular systolic/enddiastolic pressure 28.1 +/- 7.1/5.0 +/- 3.3 mmHg,
      mean pulmonary artery pressure (PAP) 15.8 +/- 4.6 mmHg, mean pulmonary wedge
      pressure (PW) 6.8 +/- 3.1 mmHg, cardiac output (CO) 5.6 +/- 2.2 L/min. and
      pulmonary vascular resistance (PVR) 150 +/- 83 dyn.sec.cm-5. During exercise (44
      pts) PAP rose from 15.8 +/- 4.3 to 29.8 +/- 9.4 mmHg, PW rose from 6.8 +/- 3.2 to
      12.6 +/- 6.8 mmHg and CO from 4.9 +/- 1.9 to 9.2 +/- 4.2 L/min. All patients
      presented with nocturnal desaturations. Mean oxygen saturation (SaO2 mean) was:
      87.4 +/- 5.4%, minimal saturation (SaO2 min) was 57.4 +/- 15.9%. Time spent in
      desaturation SaO2 < 90% (T90) was 50.7 +/- 26.5%. Results of PH investigations
      were related to results of pulse oximetry. Linear regression analysis showed week
      negative correlations between SaO2 mean and: PAP (r = -0.37 p = 0.003), PVR (r = 
      0.37 p = 0.007), and positive correlation between T90 and PAP (r = 0.37 p =
      0.008). We conclude that there is no diurnal pulmonary hypertension at rest in
      patients with severe OSA and normal lung function even in the presence of severe
      overnight nocturnal desaturations. In half of studied patients we observed
      pulmonary hypertension during exercise.

PMID- 10967900
TI  - [Effects of nocturnal desaturation on pulmonary hemodynamics in patients with
      overlap syndrome (chronic obstructive pulmonary disease and obstructive sleep
      apnea)].
AB  - We studied pulmonary haemodynamics and nocturnal desaturation in 17 patients with
      an overlap syndrome (OS), all males, mean age 51.4 +/- 8.3 years, mean BMI 37 +/-
      4.2 kg/m2. Diagnosis of COPD was based on pts history, clinical examination, lung
      function tests and chest radiography. Spirometry showed: FVC 2.7 +/- 0.7 L (59 +/
      16% N), FEV1 1.5 +/- 0.7 L (43 +/- 16% N), FEV1% FVC 54 +/- 13%, Raw 0.58 +/-
      0.4 kP.s/L, RV 3.3 +/- 1.2 L (144 +/- 51% N), TLC 6.6 +/- 1.3 L (100 +/- 14% N)
      and RV% TLC (49.5 +/- 12.1%. Arterial blood gas values were: PaO2 56.9 +/- 9.5
      mmHg, PaCO2 46.9 +/- 9.8 mmHg, pH 7.37 +/- 0.05. Mean apnoea/hypopnoea index
      (AHI) was 63.9 +/- 18.9. Pulmonary haemodynamics at rest (Swan Ganz
      thermodilution catheter) were: mean pulmonary artery pressure (PAP-SP) 24.2 +/-
      7.4 mmHg, mean pulmonary wedge pressure (PW-SP) was 9.1 +/- 7.3 mmHg, cardiac
      output (CO-SP) was 5.6 +/- 2.3 L/min. and pulmonary vascular resistance (PVR) was
      229 +/- 97 dyn.sec.cm-5. During exercise (40 Watts, 7 mins, in 8 pts) PAP rose
      from 19 +/- 6 mmHg to 41.2 +/- 15.1 mmHg, PW rose from 7.4 +/- 7.2 mmHg to 11 +/-
      10.2 mmHg, CO rose from 5.8 +/- 2.7 L/min to 12.7 +/- 2.4 L/min. Overnight pulse
      oximetry showed: mean oxygen saturation (SaO2 mean) 80.2 +/- 8.5%, minimal
      saturation (SaO2 min) was 50.7 +/- 19.7%. Time spent in desaturation SaO2 < 90%
      (T 90) was 76.9 +/- 25.7%. We conclude that pts with OS have resting pulmonary
      hypertension and elevated PVR. During low grade exercise the rise in PAP was
      highly abnormal. Statistical analysis showed no correlations between nocturnal
      SaO2 and diurnal pulmonary haemodynamics data.

PMID- 10967901
TI  - [Respiratory response to inspiratory resistive load changes in patients with
      obstructive sleep apnea syndrome].
AB  - Patients with OSA have many episodes of increased airway resistance because of
      repeated collapses of upper airways during night. The aim of this work was to
      evaluate respiratory response during chemical stimulation without and with added
      inspiratory resistive load (10 cmH2O/L/sec). The studies were performed during
      quiet breathing with air and during hypercapnic and hypoxic rebreathing tests
      without and with inspiratory resistive loading in 23 obese (BMI = 34.4 +/- 4.3
      kg/m2) patients with OSA and in 10 healthy subjects with similar weight (BMI =
      32.4 +/- 4.3 kg/m2). The measurements of respiratory responses (ventilation,
      mouth occlusion pressure) were performed with the use of computerized equipment.
      During quiet breathing in response to added load an increase of P0.1 in controls
      and in OSA patients was observed. During hypercapnic stimulation the ventilatory
      response with additional load decreased in patients as well as in controls. The
      slope of mouth occlusion pressure response increased significantly in controls
      (from 4.40 to 6.83 cmH2O/kPa, p < 0.001) and slightly weaker in OSA patients
      (from 4.21 to 5.43 cmH2O/kPa, p < 0.05). Although the difference between the
      slopes was not significant, we found that the absolute increase of P0.1 measured
      at point 8 kPa of PEtCO2 during loaded breathing was significantly smaller in OSA
      patients in comparison to controls. (2.1 vs. 10.3 cm H2O; p < 0.001). During
      hypoxic stimulation occlusion pressure responses were similar in both examined
      groups. In conclusion we postulate that OSA patients have impaired respiratory
      compensation of additional inspiratory load, what was demonstrated during
      hypercapnic rebreathing test.

PMID- 10967902
TI  - [Breast tuberculosis].
AB  - A 47-year-old woman, mother of 7 children, was admitted to hospital because of
      the painful tumour of her left breast. The clinical course was chronic with
      formation of abscess and then fistula. Chest X-ray was normal. Axillary lymph
      nodes were not palpable. During mammography tumour was revealed (3.5 cm in
      diameter). During tumour resection abscess was found. Staphylococcus aureus was
      cultured from its pus, but histologic picture of resected tissue suggested
      caseous tuberculosis of mamma. Bacilli were not found. The patient was treated
      with antituberculous drugs. At the early stage of treatment the skin fistula of
      mamma occurred but the long-lasting therapy was successful.

PMID- 10967903
TI  - [Benign clear cell tumor of the lung (sugar tumor). Morphologic,
      immunohistochemical and ultrastructural evaluation].
AB  - Clear cell tumour or "sugar tumour" of the lung is a rare primary neoplasm with
      unique histologic and electron microscopic features that may resemble those of
      metastatic renal cell carcinoma. An immunohistochemical studies are useful in a
      differential diagnosis these tumours: HMB45 in combination with a panel of
      various antibodies. The authors present a benign clear cell tumour of the lung,
      diagnosed on the base of its morphological, immunohistochemical and
      ultrastructural features.

PMID- 10967904
TI  - [Physiologic basis for using electrocardiographic R-R interval fluctuations in
      pulmonary diseases].

PMID- 10967905
TI  - [Usefulness of flow cytometric evaluation of DNA ploidy analysis in lung cancer].

PMID- 10967906
TI  - [Pneumothorax. Etiopathogenesis and treatment--current views].

PMID- 10967907
TI  - [Barbara Wardzianka (1912-1999].

PMID- 10967908
TI  - [Primary biliary cirrhosis].
AB  - Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease
      characterised by the destruction of small intrahepatic bile ducts. Although known
      for many years its etiology and pathogenesis still remains uncertain. Alterations
      of humoral and cellular immune functions suggests an autoimmune pathogenesis.
      Primary biliary cirrhosis typically affects middle-aged women who reports fatigue
      and itching. Diagnosis is usually based on abnormal biochemical tests of liver
      function, presence of antimitochodrial antibodies (especially anti-M2) and
      histologic evaluation of liver biopsy specimens. Relatively small number of
      diagnosed cases in Poland may be due to insufficient knowledge on this disease in
      our country.

PMID- 10967909
TI  - [Antibodies against M2-antigen in differential diagnosis of primary biliary
      cirrhosis].
AB  - Measurement of antimitochondrial antibodies is established as a sensitive
      indicator for primary biliary cirrhosis, which has unfortunately limited
      diagnostic specificity. M2-antigen complex, consisted of four proteins of the
      inner mitochondrial membrane, has been found to be strongly associated with PBC.
      Clinical value of anti-M2 antibodies quantitative measurement with ELISA was
      analysed in 107 patients with carefully diagnosed liver diseases: acute viral
      hepatitis A, B, C (VHA, VHB, VHC; n = 41), chronic viral hepatitis B, C (CHB,
      CHC; n = 23), autoimmune hepatitis (AH; n = 6), liver cirrhosis (LC; n = 20),
      extrahepatic cholestasis (EC; n = 2) and primary biliary cirrhosis (PBC; n = 15).
      The highest values were found in PBC patients and varied from 92 to 167 U/l and
      dramatically exceeded normal range recommended by manufacturer (5 U/l). Mean
      value in this group (119.5 +/- 8.4 U/l) was significantly (p < 5 x 10(-8)) higher
      than in others, that varied from 1.3 +/- 0.2 up to 2.8 +/- 1.7 U/l in VHA and CHC
      groups respectively. Only two among 92 non-PBC patients have values over 10 U/l,
      but they reached only 15.8 (CHB) and 16.5 (CHC). Anti-M2 level in PBC patients
      demonstrated a significant positive correlation (r = 0.857) with the degree of
      liver insufficiency measured trough Child-Pugh score. From these data we can
      conclude, that quantitative measurement of anti-M2 antibodies with ELISA can
      serve as a very good screening for PBC, with 100% diagnostic sensitivity and
      specificity, if concentration of 20 U/l will be established as a pathognomic
      level.

PMID- 10967910
TI  - [Prognostic value of natural killer cells monitoring in the course of IFN-alpha
      therapy in children with chronic hepatitis C].
AB  - The aim of this study was evaluation of the role NK cells in antiviral response
      and the monitoring IFN-alpha therapy in children with chronic hepatitis C. The
      study included 60 children between 3 and 15 years of age with chronic hepatitis C
      -30 treated and 30 not treated IFN-alpha (Intron A, Schering Plough). Percentage
      of NK cells (CD3-CD16+CD56+) was determined in all children using monoclonal
      antibodies (Becton-Dickinson) and flow cytometry before and after therapy.
      RESULTS: After IFN-alpha therapy increase of the percentage NK cells,
      significantly higher in children with elimination HCV RNA and decrease NK cells
      in children no treated was observed. These observations underline significant
      part NK cells in antiviral response and suggest that IFN-alpha ability to
      increase this cells population is an important mechanism elimination of HCV
      infection. CONCLUSION: Increase NK cells in children with chronic hepatitis C IFN
      alpha treated may be determinate effectiveness of IFN therapy.

PMID- 10967911
TI  - [Thyroid function in children with diagnosed chronic hepatitis B treated with
      interferon alpha].
AB  - The aim of the study is to estimate thyroid function during interferon alpha
      therapy in children with chronic hepatitis B. 31 children aged 4-16 years were
      included in the study. Thyroid function was monitored by estimation of thyroid
      hormones (FT3, FT4, TSH) and antithyroid antibodies (TPO, ATG) concentration
      before and after therapy completion. In all children normal thyroid hormones and
      ATG concentration were found before and after therapy completion. Presence of TPO
      before IFN treatment in blood serum of 2 girls (6.45%) and in 4 children (12.9%)
      after IFN therapy were found. Clinical features of thyroid dysfunction were not
      observed in this group of children during IFN therapy.

PMID- 10967912
TI  - [Histological evaluation of activity and progression changes in the liver in HCV
      infected children].
AB  - In this study we present the analysis of pathological pictures of the liver in
      children with chronic HCV infection, among whom 60 children with HCV RNA and 22
      children without HCV RNA were selected. For histological evaluation traditional
      classification and modified Histological Activity Index (HAI) was used. Only 2
      children without viremia did not present changes in histopathological picture, in
      the remaining ones with and without viremia hepatitis chronic persistent
      prevailed. In both groups of children statistical differences in
      necroinflammatory activity and fibrosis were not observed. In histopathological
      picture correlation grading and staging was observed. The results of the studies
      show necessity for histological evaluation in anti-HCV carriers, because the
      pathology of the liver may occur independent of viremia.

PMID- 10967913
TI  - [Lymphocytic response of gastric and duodenal mucosa in Helicobacter pylori
      infection in children].
AB  - The authors evaluated morphologically gastric and duodenal mucosa in H. pylori
      infection in children. Fenotypic evaluation of T lymphocytes carried out in
      patients showed the increase in number of these cells in gastric antrum and
      corpus mucosa in comparison with controls according to the level of mucosal
      inflammation. B lymphocytes in inflamed gastric mucosa were dispersed as lamina
      propria infiltrates or in clusters (lymph nodules).

PMID- 10967914
TI  - [Mast cell of upper gastrointestinal tract mucosa and Helicobacter pylori
      infection in children].
AB  - Using histological, immunohistochemical and electron microscopic examinations of
      gastric and duodenal mucosa the authors showed the increase in the number of mast
      cells with ultrastructural changes characteristic of their degranulation in H.
      pylori infected children. The damage of various intensification in glandular and
      covering epithelial cells and the inflammatory response were also proved. The
      results suggest the role of mastocytes in the inflammation of gastric and
      duodenal mucosa in H. pylori infected children.

PMID- 10967915
TI  - [The joint changes and presence of HLA-B27 antigen in patients with ulcerative
      colitis].
AB  - The extra-bowel manifestation can be found among patients with ulcerative colitis
      (UC). The most common are the joint changes. A group of 18 patients with
      ulcerative colitis was investigated. The physical and radiological signs of joint
      inflammation and presence of HLA-B27 antigen in blood were examined. Appearance
      of HLA-B27 antigen among 28% of patients with ulcerative colitis can support
      involvement of autoimmunologic mechanism in joint inflammation. The joint changes
      (swelling of small joints of hand, presence of nodes, sacroileitis, and
      particularly spondyloarthritis) were observed in 50% of patients.

PMID- 10967916
TI  - [The influence of Aronia melanocapra in experimental pancreatitis].
AB  - The administration of anthocyanin dyes from Aronia melanocarpa in the rats before
      the intraperitoneal injections of PAF and ceruleine have a beneficial effect on
      the development of the acute experimental pancreatitis. It was revealed the
      reduction of pancreas swelling and decreasing of lipid peroxidation and adenosine
      deaminase activity. The examination was carried out on 149, weighing 200-250 g,
      female and male Wistar rats. They lived in the animal quarters with a stable
      temperature and humidity being fed with standard fodder (Murigan) and water ad
      libitum.

PMID- 10967917
TI  - [Lipid metabolism disorders in acute pancreatitis].
AB  - On the course of acute pancreatitis which occurred in 30 patients treated in our
      clinic changes in cholesterol, triglycerides and phospholipids levels were
      monitored during 7 days of hospitalization taking into account the severity and
      aetiology of disease. The decrease of cholesterol and phospholipids levels were
      observed in 3-rd and 7-th day of hospitalization. TGs concentrations however
      showed variability regarding aetiology and severity of acute pancreatitis lack of
      mentioned above lipid levels changes before the disease onset as well as their
      rapid normalization with healing suggest, that they are rather a consequence not
      a cause of acute pancreatitis.

PMID- 10967918
TI  - [Levels of alpha-amylase, C-reactive protein and lipoprotein (a) in acute
      pancreatitis].
AB  - On the course of acute pancreatitis which occurred in 30 patients treated in our
      clinic changes in levels of alpha-amylase, C-reactive protein and lipoprotein (a)
      were monitoring during 7 days of hospitalisation talking into account the
      severity and aetiology of disease. The highest level of the alpha-amylase were
      observed in 1-st day, C-reactive protein in 3-rd day and lipoprotein (a) in 7-th
      day of observation. These parameters are very useful to monitoring course and
      heaviness of acute pancreatitis.

PMID- 10967920
TI  - [Somatic development of children who recovered from secondary malabsorption
      syndrome].
AB  - The aim of the study was to estimate somatic development of children who
      recovered from secondary malabsorbtion syndrome. We examined 24 children 2.5-13
      years old. Their weight when diagnosed was between 10-3 percentiles. Patients
      were treated with gluten free diet 8-36 month. After recovery (normal mucose in
      biopsy) 20 children (83.3%) had normal somatic development and 4 (16.7%) abnormal
      development. This abnormal development was caused by infantile cerebral palsy and
      Silver-Russel syndrome. Therapy by elimination diets gave villi regeneration and
      normal development in most of our patients.

PMID- 10967919
TI  - [Cellular immunity changes after total parenteral nutrition enriched with
      glutamine in patients with sepsis and malnutrition].
AB  - The influence of glutamine on human immune system is multidirectional but the
      exact changes still remain unclear. In this study the effect of total parenteral
      nutrition (TPN) enriched with glutamine on some selected immunological and
      nutritional parameters was examined in twelve surgical patients with sepsis and
      malnutrition. The reason for glutamine supplementation was lack of clinical
      improvement after standard TPN. All patients received TPN enriched with glutamine
      for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4,
      CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine
      administration and two days after (day 12) glutamine withdrawal. Simultaneously
      some nutritional parameters were assessed. The number and percentage of CD4,
      CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the
      same level during observation (with exception in CD4 on day 6, 12 and CD56 on day
      4). No significant differences in CD8 and HLA-DR number and percentages were
      observed after TPN enriched with glutamine. BIA examination revealed on days 2
      and 12 significant decrease of total body water and significant increase of body
      cell mass, intracellular water on day 12. It was correlated with significant
      higher total lymphocytes count and significantly higher total protein, serum
      albumin, transferrin, cholesterol and CRP concentration. Results demonstrated
      that TPN supplemented with glutamine improved rapidly some immunological and
      nutritional parameters in surgical, malnutrition patients with sepsis.

PMID- 10967921
TI  - [Melatonin in sleep rhythm disorders after cerebral stroke].
AB  - Small doses of melatonin were administrated to 30 patients with day/night rhythm
      disorders, after cerebral stroke. Psychotropic drugs administrated before did not
      bring any clinical improvement. In evaluation of melatonin the time till falling
      asleep, sleep duration, anxiety and the following day activity were taken into
      account. Good results were observed in majority of patients, concerning falling
      asleep and sleep were obtained continuity. The melatonin is a safe and worth drug
      in sleep rhythm disorders in patients after cerebral stroke.

PMID- 10967922
TI  - [Psychological and behavioral predictors of the quality of life of people with
      multiple sclerosis].
AB  - The aim of the study was to determine the relationship between some psychological
      and behavioural variables associated with disease, and health related quality of
      life. A survey was conducted on a sample of 44 people with multiple sclerosis.
      Quality of life was defined as life satisfaction and subjective assessment of
      current health status. The following methods were used: The Satisfaction With
      Life Scale (Diener et al.) and Visual Analogue Scale (single-item self-ratings of
      health) to measure the quality of life; Multidimensional Health Locus of Control
      Scale--MHLC (Wallston et al.); Acceptance of Illness Scale (Felton et al.); Self
      Esteem Scale (Rosenberg); Courtauld Emotional Control Scale (Watson and Greer)
      and Health Behaviour Inventory (Juczynski). A series of step-wise regression
      models and discriminant function analysis on future quality of life variables
      were calculated, taking as predictors psychological and behavioural variables.
      High self-esteem, engagement in a large number of health behaviour and acceptance
      of illness were most predictive of good health related quality of life of people
      with multiple sclerosis.

PMID- 10967923
TI  - [Cancer procoagulant (CP): the new biochemical marker in oncologic diagnosis].
AB  - This review describes the physicochemical and biological properties of cancer
      procoagulant (CP). This procoagulant is cysteine protease which directly
      activates coagulation factor X to factor Xa. CP is found in the tissues and blood
      of subjects suffering from cancer so its determination could be very useful in
      diagnostics and prognostics of cancer disease.

PMID- 10967925
TI  - [Disturbances of the neurohumoral regulation in patients in critical illness and
      post-resuscitation period].
AB  - Cardiac arrest (CA) is an extreme stressful situation accompanied by impairment
      of hypotalamichypophyseal axis resulting from many reasons, specially when cardio
      pulmonary resuscitation (CPR) has been delayed or prolonged. The author compares
      dysfunction of the neurohormonal system, including the release of hypophyseal and
      adrenal hormones, atrial natriuretic hormone and endothelin in patients in
      critical illness as well as in those after cardiac arrest. Associated
      consequences for the maintenance of homeostasis in postresuscitation period have
      also presented.

PMID- 10967924
TI  - [Alpha-fetoprotein: diagnostic value in hepatic disorders].
AB  - The serum AFP concentration in man falls rapidly after birth and its synthesis in
      adult life is normally repressed. However, AFP is synthesized in large amounts by
      human hepatocellular carcinoma in greater than 70% of patients. Elevation of
      serum AFP in benign hepatic diseases such as acute and chronic viral hepatitis as
      well as toxic liver injury is associated with small transient increases in serum
      AFP. Therefore, quantification of serum alpha-fetoprotein (AFP) has been widely
      used as a diagnostic marker for hepatocellular carcinoma. Measurement of serum
      AFP levels have also been used in screening populations at high risk of human
      hepatocellular carcinoma such as those with cirrhosis or carriers of hepatitis B
      virus. However the specificity of the screening test in patients with only
      modestly raised AFP (below 400 ng/ml) is low, and false-positive results are
      frequent. A wide range of overlap in the distribution of serum AFP levels between
      hepatocellular carcinoma and chronic liver disease patients were observed mainly
      among HBsAg (+) patients. Therefore the specificity and predictive value of AFP
      are lower in HBsAg(+) than in HBsAg(-) patients, especially when AFP is between
      25 and 200 ng/ml. In patients with chronic hepatitis B, the analysis of lectin
      reactivity of AFP has the advantages over quantification of serum AFP to detect
      HCC-specific variants in serum samples with only moderate raised AFP levels.
      Measurement of AFP serves as an important tool in the care and management of
      patients with benign and malignant hepatic disorders.

PMID- 10967926
TI  - [Progress in imaging diagnostics of adrenal neoplasms].
AB  - Computed tomography is the modality of choice in imaging of adrenal glands.
      Density measurements on images without contrast agent are essential for
      differentiation of adrenal masses. Application of spiral computed tomography for
      diagnostics of adrenal masses enables sensitive detection of small adrenal tumors
      and reliable density measurements by elimination of uneven breath-holds effect
      and minimization of partial volume effect. Tissue harmonic imaging in
      ultrasonography is a new technique, which enables visualization of abdominal
      parenchymal organs with higher tissue contrast with less artifacts and is
      especially useful in ultrasound imaging of difficult-to-image patients with high
      body weight. Further comparative research will enable to learn the advantages of
      using that technique in diagnostics of adrenal masses. Magnetic resonance imaging
      enables very accurate visualization diagnostics of adrenal masses. It is due to
      its inherent multiplanar imaging capabilities and high tissue contrast of soft
      tissues which enables very accurate visualization of anatomical structures in
      adrenal region. Introduction of new techniques of magnetic resonance imaging as
      chemical shift imaging and dynamic studies with paramagnetic contrast agent
      enables accurate differentiation of adrenal cortex adenomas from non-adenomas. In
      case of difficulties in adrenal diagnostics magnetic resonance imaging is often a
      problem solving examination in regard to other imaging techniques of adrenal
      region.

PMID- 10967927
TI  - [Magnetic resonance techniques used in the differentiation of adrenal tumors].
AB  - Noninvasive differentiation of adrenal masses by imaging studies as computed
      tomography and magnetic resonance imaging is an accepted diagnostic procedure in
      patients with extraadrenal neoplasm and discovered on imaging studies adrenal
      mass or in patients with incidentally discovered adrenal mass. Significant impact
      on possibilities of differentiation of adrenal masses with magnetic resonance
      imaging was due to introduction to adrenal imaging such techniques as chemical
      shift imaging and dynamic imaging with paramagnetic contrast agent.
      Differentiation of adrenal masses with magnetic resonance imaging involves
      following parameters: tumor diameter, signal intensity of adrenal mass on T2
      weighted images, lipid contents in adrenal tumor evaluated with chemical shift
      imaging and washout of paramagnetic contrast agent from adrenal mass evaluated
      with dynamic examination. The best results, reaching 100% sensitivity and 100%
      specificity in differentiation adrenal adenomas from non-adenomas, can be
      achieved by combined analysis of all mentioned parameters. In regard to
      availability and costs computed tomography not magnetic resonance imaging is the
      examination of choice in visualization of adrenal glands and their pathology and
      in differentiation of adrenal masses. Adrenal tumors on non-enhanced images with
      density below 0 Hounsfield units can reliably be diagnosed as adenomas, whereas
      adrenal tumors with density above 20 Hounsfield units can reliably be diagnosed
      as non-adenomas. Tumors with density in 0-20 Hounsfield range are ambiguous in
      character, that in many cases can be determined in magnetic resonance imaging.

PMID- 10967928
TI  - [Results of surgical treatment of congenital heart defects in infants below 2500
      grams].
AB  - We present a review of our recent experience of operating on infants below 2500 g
      suffering from congenital heart disease. A retrospective review was performed in
      73 children who had undergone cardiac operations at our institution from 1990 to
      1999. There were 43 (59%) females and 30 (41%) males; the mean age at operation
      was 28 days (range 4 to 92). The mean gestational age was 34.7 weeks (range 24 to
      41), mean birth weight--1899 g (range 700 to 2450) and mean weight at operation-
      2013 g (range 640 to 2500). Cardiac diagnoses included patent ductus arteriosus
      (PDA) (N = 21, 28.7%), ventricular septal defect (VSD) (N = 9, 12.3%),
      transposition of great arteries (TGA) (N = 10, 13.7%), tetralogy of Fallot (TOF)
      (N = 7, 9.6%), double-outlet right ventricle (DORV) (N = 4, 5.5%), truncus
      arteriosus communis (TAC) (N = 4, 5.5%), hypoplastic left heart syndrome (HLHS)
      (N = 4, 5.5%), coarctation of aorta (CoAo) (N = 6, 8.2%), total anomalous
      pulmonary venous return (TAPVR) (N = 2, 2.7%), aortic stenosis (AoVS) (N = 3,
      4.1%), interrupted aortic arch (IAA) (N = 1, 1.4%), pulmonary atresia (PA) (N =
      1, 1.4%) and common atrioventricular canal (CAVC) (N = 1, 1.4%). Hospital
      mortality was 16.4%. There were 6 early deaths (8.2%) and 6 late deaths (8.2%). A
      higher mortality rate was noted in premature children and in children who had
      undergone palliative procedures. At a 1-116-month follow-up (mean 39 months), of
      57 (93.4%) patients, 46 (80.7%) were in NYHA class I and 11 (19.3%) in NYHA class
      II. In conclusion the authors believe that early intervention can be performed in
      infants below 2500 g, and the associated mortality and morbidity rates are low.

PMID- 10967929
TI  - [Propolis: its properties and administration to patients treated for some
      surgical diseases].
AB  - The authors tested a bee-hive product propolis as a drug to treat patients
      operated for goitre, patients with wounds and ulcerations difficult to heal and
      patients with non-specific rectal inflammation. They also tested the
      effectiveness of propolis as supplementary means in eradicating treatment of
      Helicobacter pylori. It was found that the drug was tolerated very well,
      practically had no side-effects and was highly effective. Preparations of
      propolis can be successfully used in surgery.

PMID- 10967930
TI  - [Does the laparoscopic technique influence the intraperitoneal tumor
      dissemination?].
AB  - Rapid tumour growth after laparoscopic surgery is a rare and mysterious problem.
      In seven years period (October 1992-31 June 1999) in the 2nd Department of
      Surgery at the Jagiellonian University in Cracow, we observed seven persons (five
      women and two men aged 45 to 70 years), who in short time after laparoscopic
      cholecystectomy, developed intra-abdominal cancer dissemination. In all cases
      before and during the operation gallbladder was unsuspected. In five patients,
      gallbladder cancer (T3) was found in routine postoperative microscopic
      examination. 18 to 65 days after laparoscopic cholecystectomy patients were
      operated on and in all cases reexcision was impossible because of micronodular
      tumour dissemination in peritoneal cavity. The next woman, six months after
      laparoscopic cholecystectomy, gastric cancer was diagnosed, and during the
      operation we found intraperitoneal micro-nodular tumour growth. Last patient 4
      months after laparoscopic hernioraphy and cholecystectomy had pancreatic cancer
      subsequently portsite metastasis and intraabdominal cancer dissemination.
      CONCLUSIONS: Rapid tumour dissemination in peritoneal cavity after laparoscopic
      cholecystectomy is probably a consequence of laparoscopic technique.

PMID- 10967931
TI  - [Chronic inflammation of the colon: a diagnostic problem].
AB  - Chronic inflammation of the colon and rectum with associated diarrhea has become
      more difficult to diagnose recently. Many etiological factors and different
      therapeutic outlines need to be carefully discussed and summarized. Based on most
      recent literature, authors present current data on etiology and specific (case
      depended) diagnostic procedures in colitis and proctocolitis.

PMID- 10967933
TI  - [Psychological aspects of postop pain].
AB  - Pain has an important role to play as a warning signal against disease or tissue
      injury, yet is perceived as one of the most unpleasant and complex sensations.
      Since it is usually accompanied by nervousness, anxiety and other negative
      emotions, return to health can be longer than necessary. Hence much attention is
      paid to medical interventions which allow pain relief or a total elimination
      thereof. In some circumstances, however, they may be inadequate, that is why
      other, extra-medical factors are being explored. Man is a psychosomatic being,
      consequently, no somatic changes can happen without the involvement of the
      psychological sphere. In the case of surgical procedures, methods of
      psychological preparation and patient support play an important role in recovery.

PMID- 10967932
TI  - [Pathophysiology of postoperative pain].
AB  - The rapid progress in neurophysiology and neuropharmacology has made it possible
      to understand an entire series of pain-related processes. The discovery of
      endogenic opioid system, the noradrenergic and serotoninergic antinociceptive
      systems, peripheral opioid receptors and of the role of NMDA, muscarinic and
      nicotinic receptors in nociception allowed for an optimization of pain treatment
      through the use of new drugs and therapies. An appropriate pain treatment
      procedure prevents the development of persistent postoperative pain, which is
      described as a pathological chronic pain that endures following the operation
      despite normal healing process having taken place in affected tissues.

PMID- 10967934
TI  - [Pharmacotherapy of postoperative pain].
AB  - In recent years there has been much progress in the understanding of the
      pathophysiology of acute pain and analgesic pharmacology. The most important role
      in postoperative pain management is still played by opioids administered through
      various modes, including spinal and local ones. However, non-opioid analgesics,
      i.e. non-steroid anti-inflammatory drugs and paracetamol are more and more
      frequently used in the management of postoperative pain, which is the result of,
      among other factors, the appearance on the market of intravenous forms of those
      drugs. Paracetamol, owing to its safe therapeutical profile, should be the
      primary postoperative pain management tool in a majority of surgical procedures.
      A combination of opioids, NSAIDs and paracetamol in order to relieve pain allows
      both for a significant reduction in the dosage of respective drugs, fewer side
      effects and an improved pain relief.

PMID- 10967935
TI  - [Postoperative pain treatment].
AB  - Postoperative pain, arising due to surgical tissue injury, is most frequent type
      of pain found in clinical practice. In postoperative analgesia opioids still
      constitute the fundamental form of pain treatment, but the development of
      neurophysiology and neuropharmacology has allowed for the optimization of
      postoperative analgesia. Therefore, in order to potentialize the pain relief
      effect of opioids and/or inhibit the nociception process and its consequences,
      diverse drugs and therapies are used. The procedure is called multimodal
      analgesia and consists in the administration of opioids in conjunction with NMDA
      antagonists, COX inhibitors, cholecystokinin antagonists, agonists of muscarine
      receptors, agonists of alpha-2 receptors or cytokine inhibitors. An alternative
      or supplementary therapy in the postoperative period relies on local anaesthetic
      techniques or TENS. There also exists pre-emptive analgesia, whose aim is to
      safeguard the central nervous system from increased afferent nociceptive
      stimulation during the operation.

PMID- 10967936
TI  - [Postop pain treatment in children].
AB  - In last years there has been an increasing consideration of pain and it's
      treatment in children. Pain is difficult to measure precisely and reliably in
      children and this has led to the proliferation of a multiplicity of pain
      measurement scores for neonates, infants and children. Most pain measurement
      scores try to assign a numerical value to just one of these dimensions:
      cognitive, physiological, sensory, behavioural, affective, sociocultural and
      environmental factors all affect pain assessment. Anesthesiologists are
      adequately trained and sensitive to the manifestations of acute pain in various
      age groups and are experienced in intervening safely, effectively and
      appropriately to control the pain. All children should be regularly assessed for
      the presence of pain, its intensity and its cause. Titration of analgesia to
      control pain and documentation of the efficacy and adverse effects of pain
      management should be routine in all age groups. Whichever scoring system is used,
      the assessments should be repeated regularly, appropriate interventions should be
      prescribed and their effectiveness in reducing the pain severity should be
      regularly documented.

PMID- 10967938
TI  - [Zygmunt Szantroch: Krakovian anatomist of the war period].
AB  - Z. Szantroch (Szantroch) professor of anatomy of the Medical Faculty of the
      Jagiellonian University 1936-1939. The main interest: structure and formation
      sympathetic nervous system. He was murdered in 1940.

PMID- 10967937
TI  - [Pregnancy in patients with end-stage renal failure on maintenance dialysis: case
      reports].
AB  - Pregnancy in women with end-stage renal failure on maintenance dialysis is rare,
      and the chance of successful delivery is relatively low. In this paper we present
      two cases of women who conceived just prior to initiation of renal replacement
      therapy and the pregnancy was terminated successfully already on chronic dialysis
      treatment. The special attention was paid on the necessity of multi-disciplinary
      collaboration and the need for changes in regular dialysis schedule as the
      conditions crucial for successful delivery. In summary, the review of current
      literature dealing with mentioned problem was done.

PMID- 10967939
TI  - Being there.

PMID- 10967940
TI  - ACE inhibitors: new hope for old drugs?

PMID- 10967941
TI  - [Instruments for quality control in management of severely injured patients].
AB  - This article describes the most important scoring systems in trauma care and
      their application to quality control. Development and contents of the Glasgow
      Coma Scale (GCS), Abbreviated Injury Scale (AIS), Injury Severity Score (ISS),
      Trauma Score (TS), Revised Trauma Score (RTS) and of the TRISS-method are
      described. The advantages and the limitations of the mentioned scoring systems
      are discussed critically.

PMID- 10967942
TI  - [Liver resection for liver metastases--1998 Bern Symposium].
AB  - The increasing knowledge of the anatomy and function of the liver made the
      surgical resection of liver metastases currently to the therapy of choice.
      Although liver metastasis is an advanced stage in tumor-progression, surgery
      achieves the best long-term results due to a better understanding of the
      carcinogenesis (i.e. micrometastases) and the prognostic risk factors. This study
      summarizes the results of 109 resections of colorectal and non-colorectal liver
      metastases during a period of 59 months at our department. Four different
      surgical techniques (extended hepatectomy vs. segmental resection vs. atypical
      resection vs. biopsy) were investigated. For resections a tumour-free resection
      margin of at least 10 mm was always attempted to achieve. The accumulated
      morbidity of all techniques together was 23%. Although the morbidity was higher
      for extended resections (Encephalopathy 16% vs. 2.3% for segmental resections,
      Liver insufficiency 23% vs. 4.7%), compared to the limited resection procedures,
      the long-term survival improved. The overall mortality was 2.7%. Survival was
      higher in patients with resection of colorectal than non colorectal metastases.
      Our results indicate that liver resection, under observance of the anatomical and
      functional margins (i.e. an adequate resection margin), is the only potentially
      curative therapy for liver metastases. An extensive formal resection, although
      inducing a higher perioperative morbidity, is superior to the limited resection
      techniques and results in an increased long-term survival. One reason is the
      increased probability of co-resection of preoperatively undetected local
      micrometastases.

PMID- 10967943
TI  - Diagnostic value of interleukin-6 and C-reactive protein in acute appendicitis.
AB  - The aim of this study is prospectively to evaluate the serum C-reactive protein
      (CRP) and interleukin-6 (IL-6) levels in detection of acute appendicitis in
      patients with right iliac fossa pain. Data were collected in prospective manner
      on 102 consecutive patients with right iliac fossa pain. Laparotomy was performed
      for suspected acute appendicitis for 55 of the 102 patients, of whom 49 patients
      had appendicitis, 6 patients non-appendicitis (NA), and the other 47 patients had
      nonspecific abdominal pain (NSAP) and they did not undergo operation. Among those
      with appendicitis 31 had acute appendix (AA), 8 had gangrenous appendix (GA), and
      10 had perforated appendix (PA). The WBC and CRP the mean (SEM) values were
      significantly different in AA, GA, and PA groups compared with NSAP and NA groups
      (P < 0.05). Although the mean IL-6 levels were significantly different only in PA
      group than the others groups (P < 0.05). The sensitivity and specificity of serum
      CRP measurements were calculated as 96% and 87%, respectively whereas these were
      33% and 83% for IL-6 levels for the diagnosis of the acute appendicitis. As a
      result, measurement of the CRP levels and WBC have an additional diagnostic value
      on the diagnosis of the acute appendicitis but determination of IL-6 levels which
      added to the test combination of WBC and CRP, the sensitivity for the diagnosis
      of the acute appendicitis was not changed whereas the specificity was decreased
      to 66%.

PMID- 10967944
TI  - [Secondary hyperparathyroidism: pathophysiology and therapy--follow-up analysis
      of patients of the Chur dialysis department].
AB  - Between 1982 and 1998 12 chronic dialysis patients treated at the dialysis unit
      of Kantonsspital Chur were operated for secondary hyperparathyroidism (HPT). In
      10 patients total parathyroidectomy with autotransplantation of parathyroid
      tissue was performed. Two patients had subtotal parathyroidectomy. Patient data
      were retrospectively analyzed in regard to indication, operation techniques,
      pharmacological therapy and possible recurrence or persistence of HPT. Four
      patients had normal PTH levels upon follow up. The parathyroid function was
      judged "equivocal" in three patients, the average PTH being to high (1), normal
      (1) and too low (1). One patient showed moderate hyperparathyroidism. Two
      patients developed recurrence of HPT one of which was sufficiently severe to
      necessitate reoperation at the autotransplantation site. In the first two
      operated patients the data are missing. Compared with other studies the rate of
      recurrence is higher in our series. Intraoperative ultrasound and improving
      diagnosis of the frozen sections could possibly favorably influence outcome.

PMID- 10967945
TI  - [Recurrent hyperparathyroidism in kidney failure patients after total
      parathyroidectomy and autotransplantation. Case report and review of the
      literature].
AB  - We present the case of a 57-year old man who underwent total parathyroidectomy
      with autotransplantation into the brachioradial muscle (Wells' method) due to
      secondary hyperparathyroidism as a complication of chronic renal failure. Three
      years later the patient developed recurrent secondary hyperparathyroidism due to
      graft hyperplasia resulting in the removal of the graft. We point out various
      problems associated with Wells' method and discuss alternative surgical
      techniques.

PMID- 10967946
TI  - Primary small bowel carcinoma--case report.

PMID- 10967947
TI  - [Ogilvie syndrome with cecal perforation. A rare complication after isolated
      thoracic trauma. Case report and current literature review].
AB  - In reviewing 750 cases of acute colonic pseudo-obstruction from the literature,
      the most commonly associated disorders are listed and the therapeutical
      management is critically discussed. The authors describe an additional case of a
      77-year-old male with ogilvie's syndrome following isolated thoracic trauma.
      Ogilvie's syndrome has been used synonymously with acute colonic pseudo
      obstruction (ACPO) of the colon, first defined by Sir Heneage Ogilvie in 1948. If
      inappropriately managed, the massive colonic dilatation may lead to caecal
      ischaemia and perforation with a high mortality rate. Aetiology and pathogenesis
      of the syndrome are still unknown, but mostly ACPO is associated with a wide
      variety of medical conditions. Often it appears to be a complication after
      abdominal or pelvic surgery or trauma. In few cases the pseudo-obstruction is
      isolated and therefore truly idiopathic. Conservative treatment is indicated if
      the caecum is less than 12 cm in diameter. If there is a progressive increase in
      diameter or no improvement is seen, the colon should be decompressed without
      further delay. The indications for surgery are failure of conservative treatment
      and colonoscopy, signs for ceacal ischaemia or perforation. The choice of
      procedure, coecostomy or resection, is dictated by the state of the caecum. Due
      to a high mortality rate (up to 50%) if the caecum is perforated, an aggressive
      therapeutical management should be applied.

PMID- 10967948
TI  - [An alternative for defect coverage of the dorsal side of the finger with a
      pedicled flap].
AB  - We present a flap to cover defects of the dorsum of the digits with donor site at
      the midhand. It may be used by leek of the donor sites of established
      alternatives i.e. cross-finger flap or an island flap. The flap can size up to 8
      x 2 cm, its pedicle is formed by the Vasa perforantia distales of the webspace 2
      4. It is inset into the primary defect by rotation of 180 degrees and reaches
      easily defects beyond the PIP joints.

PMID- 10967949
TI  - Can life be evaluated? The Jewish Halachic approach vs. the quality of life
      approach in medical ethics: a critical view.
AB  - In recent years there has been an increase in the number of requests for "mercy
      killings" by patients and their relatives. Under certain conditions, the patient
      may prefer death to a life devoid of quality. In contrast to those who uphold
      this "quality of life" approach, those who hold the "sanctity of life" approach
      claim that life has intrinsic value and must be preserved regardless of its
      quality. This essay describes these two approaches, examines their flaws, and
      offers a "golden path" between the two extreme positions. We discuss the halachic
      and the secular views, arguing for a balance between the sanctity of life and the
      quality of life. We argue that, indeed, such a balance exists in practice, and
      that life is important, but it is not sacred. Life can be evaluated, but quality
      of life is not the sole criterion.

PMID- 10967950
TI  - Why the practice of medicine is not a phronetic activity.
AB  - This essay argues that the practice of medicine is not a phronetic activity in
      the original Aristotelian sense of that term. Jonsen and Toulmin are two
      philosophers who have conflated the techne of medicine with phronesis. This
      conflation ignores Aristotle's crucial distinction between techne and phronesis
      and his use of the medical analogy. It is argued that medical reasoning is
      similar to phronesis but does not exemplify it. Phronesis will not save the life
      of medical ethics. The concept could be utilized as a moral prosthetic.

PMID- 10967951
TI  - Ethical issues in gestational surrogacy.
AB  - The introduction of contraceptive technologies has resulted in the separation of
      sex and procreation. The introduction of new reproductive technologies (mainly
      IVF and embryo transfer) has led not only to the separation of procreation and
      sex, but also to the redefinition of the terms mother and family. For the purpose
      of this essay, I will distinguish between: 1. the genetic mother--the donor of
      the egg; 2. the gestational mother--she who bears and gives birth to the baby; 3.
      the social mother--the woman who raises the child. This essay will deal only with
      the form of gestational surrogacy in which the genetic parents intend to be the
      social parents, and the surrogate mother has no genetic relationship to the child
      she bears and delivers. I will raise questions regarding medical ethical aspects
      of surrogacy and the obligation(s) of the physician(s) to the parties involved. I
      will argue that the gestational surrogate is "a womb to rent," that there is
      great similarity between gestational commercial surrogacy and organ transplant
      marketing. Furthermore, despite claims to freedom of choice and free marketing, I
      will claim that gestational surrogacy is a form of prostitution and slavery,
      exploitation of the poor and needy by those who are better off. The right to be a
      parent, although not constitutional, is intuitive and deeply rooted. However, the
      issue remains whether this right overrules all other rights, and at what price to
      the parties involved. I will finally raise the following provocative question to
      society: In the interim period between today's limited technology and tomorrow's
      extra-corporeal gestation technology (ectogenesis), should utilizing females in
      PVS (persistent vehetative state) for gestational surrogacy be socially
      acceptable/permissible--provided they have left permission in writing?

PMID- 10967952
TI  - Hermeneutics of clinical practice: the question of textuality.
AB  - In this article I scrutinize the question whether clinical medicine, in order to
      be considered a hermeneutical enterprise, must be thought of as a reading of
      different "texts." Three different proposals for a definition of the concept of
      text in medicine, suggested by other hermeneuticians, are discussed. All three
      proposals are shown to be unsatisfying in various ways. Instead of attempting to
      find a fourth definition of the concept of text suitable to a hermeneutics of
      medicine, I then try to show that the assumption that one needs to operate with
      the concept of text in order to develop a hermeneutics of medicine is false.
      Clinical interpretation can be shown to essentially consist in a dialogical
      hermeneutics, the pattern of which can be found in the philosophy of Hans-Georg
      Gadamer. This kind of hermeneutics is not a methodology of text reading, but an
      ontological, phenomenological hermeneutics in which understanding is a necessary
      feature of the being-together of human beings in the world. This being-together
      in and through language takes on a peculiar form in the clinical encounter, since
      the medical meeting is typically characterized by an asymmetrical enstrangement
      and has a specific goal--health for the patient--absent in other forms of
      hermeneutics. Central issues of Gadamer's philosophy, e.g. "fusion of horizons,"
      are shown to fit the structure of clinical practice.

PMID- 10967954
TI  - [A traditional farming environment--a prophylactic factor against allergies].

PMID- 10967953
TI  - Schizophrenia epigenesis?
AB  - I begin by examining how genetics drives schizophrenia research, and raise both
      familiar and relatively novel criticisms of the evidence putatively supporting
      the genetic basis of schizophrenia. In particular, I call attention to a set of
      concerns about the effects of placentation on concordance rates of schizophrenia
      in monozygotic twins, which further weakens the case for schizophrenia's so
      called strong genetic component. I then underscore two critical points. First, I
      emphasize the importance of taking seriously considerations about the complexity
      of both ontogenesis and the development of hereditary diseases. The recognition
      of developmental constraints and supports is crucial, for attention to
      development exposes the naivete of too many models of gene action in the
      aetiology of disease. Secondly, I attend to those schizophreniologists who ignore
      methodological criticisms and thus presume a genetic basis for schizophrenia, and
      then seek the 'schizophrenic genotype' lacking an adequate phenotype. In response
      I attempt to demonstrate the necessity of a sustained effort at characterizing
      the phenotype of schizophrenia as an enabling condition for the whole enterprise
      of psychiatric genetics--and for psychiatry itself. Without the organism-level
      phenotype, research at the level of genes will remain unproductive--assuming of
      course that research at the genetic level is appropriate at all.

PMID- 10967955
TI  - [Farmers' children suffer less from hay fever and asthma].
AB  - BACKGROUND: Farm children suffer less frequently from pollinosis and bronchial
      asthma, although they are exposed to higher concentrations of airborne allergens.
      How do farm children differ from children in the general population with respect
      to immunological sensitization to airborne allergens? METHODS: Since 1983, a
      continuing seroepidemiological study of allergic reactions of schoolchildren in a
      rural area was conducted. Each year, all 15 year-old schoolchildren were given a
      standardized allergy questionnaire and are tested serologically (RAST/CAP-test)
      for their IgE sensitization towards the four major groups of airborne allergens:
      timothy grass pollen, birch pollen, house-dust mites, and cat dander. Farm
      children were compared with children who only occasionally help out on farms and
      also with those who had no direct contact with agriculture. RESULTS: From a total
      of 1307 children, 1287 questionnaires (98.5%) and 1100 (84.2%) of the serological
      tests could be analysed. Over the 16 years of the study, a statistically
      significant increase in the incidence and severity of hay fever and asthma was
      found in the children with no direct contact to agriculture. This was coupled
      with a significant increase in the sero-prevalence of sensitisation to the major
      airborne allergens. Among the 133 farm children, the prevalence of hay fever was:
      any history of hay fever in 2.4%, hay fever within the last year in none. A
      history of asthma was found in 1.6% of the children. Among children who
      occasionally worked on or had contact with farms, the prevalences were: any
      history of hay fever 9.3%, hay fever within the last year 9.3%, asthma 4.4%.
      Corresponding prevalences in children with no direct contact to farms were 18.3%,
      18.6% and 9.1%, respectively. The seroepidemiological tests showed that the farm
      children not only had an overall lower rate of seroprevalence of antibodies
      towards the 4 marker allergens, but they also became sensitized to a lesser
      extent. At increasing cut-off values of the specific IgE titers, the odds ratio
      of the farm children in comparison to the control children became increasingly
      significant. This trend was found with all four marker allergens. The paradoxical
      immune reaction of farm children towards airborne allergens shows two
      characteristic quantitative features: in spite of high exposure rates, the
      children became sensitized less often and more weakly than control classmates
      from the same village. Children who had intermittent contact with farms showed
      intermediate results with respect to both symptoms and sensitization.
      CONCLUSIONS: These farm children have thus become adapted towards the allergens
      to which they are exposed. This immunological form ist similar to results from
      East Germany and the former USSR, in spite of the fact that lifestyle and
      exposure to microbes differ greatly. The immunological adaptation can best be
      interpreted as the result of a greater and continual stimulation of the Th1
      immune response towards anthropozoonotic antigens.

PMID- 10967956
TI  - [First diagnosis of celiac disease in a 67-year old female patient].
AB  - HISTORY AND CLINICAL FINDINGS: A 67 year old female patient presented herself to
      our emergency room with paraesthesia in both hands, chronic diarrhea and
      continuous weight loss. From the past medical history, only an autoimmune
      hypothyroidism was known. On initial, examination leading features were
      carpopedal spasms and a pulse deficit. Her general condition, especially the
      nutritional status was low. INVESTIGATIONS: Serum levels of potassium (2.2
      mmol/l) and calcium (1.45 mmol/l) were low, as well as the levels of total
      protein (5.1 g/dl) and albumin (2.94 g/dl). Clotting time was prolonged (Quick
      51%). The ECG showed a ventricular bigeminus and a prolonged QT-period (120%
      rel). Endoscopy and biopsy showed a total villous atrophy suggesting celiac
      disease as probable cause. This was emphasized by the high antibody levels
      against gliadin (1:80) and endomyosin (1:40). Furthermore, the Human Leukocyte
      Antigen molecules HLA-B8 and HLA-DR3 showed increased expression. TREATMENT AND
      COURSE: After normalizing the electrolyte imbalance intravenously the
      neurological symptoms disappeared as well as the arrhythmia. The QT-period went
      back to normal. Under initial drip feeding and a strict gluten-free diet the
      general condition improved quickly and the diarrhea stopped. A follow-up
      investigation 3 months later showed the woman in a good condition having gained
      10 kg weight and an improvement in histological findings, so that diagnosis of
      celiac disease could be proved. CONCLUSIONS: The possibility of ventricular
      arrhythmia and a prolonged QT-period in the ECG should be taken into account for
      patients diagnosed with celiac disease, especially in case of electrolyte
      imbalance. In these cases addition to a strict gluten free diet a rapid
      correction of the electrolyte imbalance is necessary because of the risk of
      sudden cardiac death. Furthermore associated disorders like autoimmune diseases
      expressing the same HLA-antigens (HLA-B8 and HLA-DR3) must be considered.
      Combined incidence of celiac disease and autoimmune hypothyroidism is well
      documented. For patients with celiac disease we therefore recommend a routine
      testing of thyroid hormone levels.

PMID- 10967957
TI  - [Clopidogrel].

PMID- 10967958
TI  - [p53 autoantibodies in clinical diagnosis].

PMID- 10967959
TI  - [Cardiomyopathy in obesity--a disease entity?].

PMID- 10967960
TI  - [Nocturnal bronchial obstruction, sleep and vigilance--is there an interaction?].

PMID- 10967961
TI  - [Thomas Mann and medicine. An inquiry on his 125th birthday].

PMID- 10967962
TI  - [Amoxicillin/clavulanic acid].

PMID- 10967963
TI  - [Favorable long-term outcome with mistletoe therapy in a patient with
      centroblastic-centrocytic non hodgkin lymphoma].

PMID- 10967964
TI  - The antifungal action of dandruff shampoos.
AB  - The disease commonly known as "dandruff" is caused by numerous host factors in
      conjunction with the normal flora yeast Malassezia furfur (Pityrosporum ovale).
      Indeed, clinical studies have shown that administration of antifungal agents
      correlates with an improved clinical condition. Almost all commercially available
      hair shampoos publicize that they contain some form of antifungal agent(s).
      However, few studies have been published in which antifungal activity of
      commercially available hair shampoos have been contrasted experimentally. In this
      study six commercially available shampoos (in the Philippines) were assessed for
      antifungal activity against a human (dandruff) isolate of M. furfur: (a) Head &
      Shoulders (Proctor & Gamble); (b) Gard Violet (Colgate-Palmolive); (c) Nizoral 1%
      (Janssen); (d) Nizoral 2% (Janssen); (e) Pantene Blue (Proctor & Gamble); and (f)
      Selsun Blue (Abbott). The results demonstrated that all six of the assayed hair
      shampoos have some antifungal effect on the test yeast. However, there was
      consider variation in potency of antifungal activity. Nizoral 1% and Nizoral 2%
      shampoo preparations were the most effective. The 1% Nizoral shampoo was
      consistently 10X better at killing yeast cells than the next closest rival
      shampoo. The 2% Nizoral shampoo was 10X better than the Nizoral 1% product and
      100 times better than any of the other products assayed. The study demonstrated
      that shampoos containing a proven antifungal compound were the most effective in
      controlling the causative yeast.

PMID- 10967965
TI  - Field ecology of the ochratoxin A-producing Penicillium verrucosum: survival and
      resource colonisation in soil.
AB  - A field experiment was conducted to elucidate the survival of P. verrucosum in
      infested bulk soil (T1) and infested soil with waste grain (T2). The infested
      soil and reference soil (T3) was filled into steel cylinders, which were buried
      and sampled 13 times during a period from October 1994 to March 1996. The
      abundance of P. verrucosum and indigenous soil fungi were assessed by dilution
      plating on a selective and diagnostic medium (DYSG). Kernel infection was
      examined in T2. According to our results, P. verrucosum seems well adapted to
      survival in arable soil and little affected by indigenous fungi. During the first
      autumn and winter the grain caused a proliferation of P. verrucosum while its
      abundance in bulk soil was more constant except for a decrease in February 95,
      which is ascribed to frost/thaw alternations. In T2, P. verrucosum initially
      infected more than 50% of the kernels but during the first few months it was
      ousted by other fungi. A hypothesis regarding waste grain as the natural niche
      for the fungus in the field was therefore partly rejected. A gradual decrease in
      the abundance of P. verrucosum in soil during spring, a die-off in the dry summer
      and a proliferation during the second winter were found in both T1 and T2. Our
      results cannot provide the reason for the increase during the second winter. On
      an overall basis, however, they show that P. verrucosum can survive in the field,
      proliferate on soil organic matter and probably become an integral part of the
      soil ecosystem. This may constitute a risk of grain contamination when given
      appropriate environmental conditions.

PMID- 10967966
TI  - Suppression of spore germination and aflatoxin biosynthesis in Aspergillus
      parasiticus during and after exposure to high levels of phosphine.
AB  - Agar cultures of toxigenic Aspergillus parasiticus NRRL 2999 were exposed to
      phosphine (PH3), in levels ranging from 0 to 2000 ppm (vol/vol). It was found
      that with PH3 concentrations of 400 ppm or higher the growth of the fungus was
      totally arrested. When PH3 was vented and the agar plates were exposed to open
      air, 100% of the initial CFU developed into fully grown colonies after PH3 levels
      below 300 ppm, but at higher PH3 concentrations only 50% of the colonies
      developed. The same strain of A. parasiticus was inoculated into high moisture
      corn under conditions highly favorable for aflatoxin production, and it was
      exposed to a range of PH3 levels. After exposure to 500 ppm PH3, both fungal
      growth and aflatoxin synthesis resumed shortly after elimination of the toxic
      gas, but after exposure to PH3 levels of 1000 ppm and higher, the physical
      appearance of the contaminated corn was remarkably changed, showing reduced
      mycelial growth and almost complete absence of green pigmentation. In addition,
      aflatoxin synthesis was totally absent for the remainder of the experiment (20
      days). These results strongly suggest that exposure to PH3 levels of 1000 ppm or
      higher could bring about persistent metabolic changes in surviving Aspergillus
      organisms.

PMID- 10967967
TI  - Production of T-2 toxin by a Fusarium resembling Fusarium poae.
AB  - A Fusarium species with a micro morphology similar to F. poae and a metabolite
      profile resembling that of F. sporotrichioides has been identified. Like typical
      F. poae, the microconidia have a globose to pyriform shape, but the powdery
      appearance, especially on Czapek-Dox Iprodione Dichloran agar (CZID), less aerial
      mycelium and the lack of fruity odour on Potato Sucrose Agar (PSA) make it
      different from F. poae. The lack of macroconidia, polyphialides and
      chlamydospores differentiates it from F. sporotrichioides. All 18 isolates
      investigated, 15 Norwegian, two Austrian and one Dutch, produced T-2 toxin (25
      400 micrograms/g) on PSA or Yeast Extract Sucrose agar (YES). In addition,
      neosolaniol, iso-neosolaniol, HT-2 toxin, 4- and 15-acetyl T-2 tetraol, T-2 triol
      and T-2 tetraol and 4,15-diacetoxyscirpenol were formed in variable amounts.
      Neither nivalenol, 4- or 15-acetylnivalenol or 4,15-diacetylnivalenol were
      detected in any of the cultures, while these toxins were produced at least in
      small amounts by all the 12 typical F. poae isolates studied. The question of
      whether this Fusarium should be classified as F. poae or F. sporotrichioides or a
      separate taxon should be addressed.

PMID- 10967969
TI  - Repressor-AFLR interaction modulates aflatoxin biosynthesis in Aspergillus
      parasiticus.
AB  - Regulation of aflatoxin (AF) biosynthesis likely involves a complex interplay of
      positive- and negative-acting factors that are affected by physiological cues
      responsive to internal and external stimuli. These factors, presumably, modulate
      the expression of the AF pathway-specific regulatory gene, aflR, whose product,
      AFLR, a zinc cluster transcription factor, then turns on or off the transcription
      of other AF genes. To determine if the AFLR carboxyl region (AFLRC) interacts
      with positive- or negative-acting proteins, we fused the Aspergillus parasiticus
      aflR carboxyl coding region (aflRC) to the promoter of A. parasiticus nitrite
      reductase gene (niiA(p)::aflRC), and transformed it into A. parasiticus SRRC
      2043. Transformants that contained two copies of niiA(p)::aflRC, one at the niaD
      locus and another at the aflR locus, overproduced AF precursors independent of
      the nitrogen source. The higher copy number of the integrated niiA(p)::aflRC
      correlated with increased production of AF precursors by the transformants as
      well as increased expression of both aflRC and native aflR in potato dextrose
      broth and A&M medium. Since aflRC does not encode a DNA-binding domain, the
      expressed AFLRC should not bind to the promoters of AF pathway genes and affect
      transcription directly. The results are consistent with AFLRC titrating out a
      putative repressor that interacts with AFLR under different growth conditions and
      modulates AF biosynthesis. This interaction also indirectly affects sclerotial
      development.

PMID- 10967968
TI  - Mycotoxin production by Fusarium proliferatum isolates from rice with Fusarium
      sheath rot disease.
AB  - Twenty samples of unpolished (rough) rice collected in Arkansas and Texas during
      the 1995 harvesting season from fields exhibiting Fusarium sheath rot disease or
      panicle blight were previously shown to include 8 samples positive for fumonisin
      B1 (FB1) in the range 2.2-5.2 ppm, and moniliformin (MON), but no beauvericin
      (BEA), deoxynivalenol, its derivatives or zearalenone were detected. Fifteen
      cultures of F. proliferatum were established from the 20 rough rice samples.
      Single spore isolates of each culture were grown on rice and tested for the
      production of fumonisins (FB1, FB2, FB3, etc.), MON and BEA. All 15 isolates
      produced FB1, FB2, MON and BEA in culture on rice. No deoxynivalenol, its
      derivatives or zearalenone were detected. Seven cultures produced FB1 at > 50 ppm
      (range 80-230 ppm), with the rest producing FB1 in the range 14-43 ppm. FB2 was
      produced in the range 5-47 ppm, and those cultures which produced the most FB1
      also produced the most FB2. Of the 15 cultures producing MON, 11 produced it at >
      100 ppm in the range 188-6018 ppm, with the rest producing in the range 7-64 ppm.
      BEA was produced in the range 109-1350 ppm. Other derivatives of fumonisins,
      including FA1, FA2 and partially hydrolyzed FB1, as well as several unknown
      metabolites including a compound with MW 414, were identified in culture extracts
      by continuous flow fast atom bombardment with ion spray mass spectrometry
      (CF/FAB/MS). Further study is needed to identify the factors that control
      production of FB1, MON and BEA by F. proliferatum in culture and in field
      samples.

PMID- 10967971
TI  - Emerging infections: the threat to Malaysia.

PMID- 10967970
TI  - Infectious diseases in England and Wales: April to June 1999.

PMID- 10967972
TI  - Microbial diseases in Malaysia: recent experiences.
AB  - Microbial diseases continue to occur in Malaysia despite the marked socio
      economic development that has been taking place in the country along with
      improvements in the medical, health, and environmental sectors. This paper
      highlights the continuing presence of the numerous microbial diseases including
      the emergence of new problems such as AIDS. Local publications dealing with work
      on several microbial diseases is reviewed to show that this group of diseases
      will pose challenges for a long while. Undoubtedly several other diseases that
      were relatively unrecognised in the past are increasingly being identified owing
      to recent availability of diagnostic facilities and equipments. The need for
      continued vigilance is emphasised.

PMID- 10967973
TI  - Screening for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the commonest cancers in Asian males. In
      Malaysia, it is one of the ten most common cancers amongst the male population.
      Most of our patients with HCC present to us rather late and almost all die within
      4 months of diagnosis. HCC occurs more commonly in patients with cirrhosis
      associated with hepatitis B and C infections. Screening for HCC can lead to early
      detection of small tumours (< 5 cm) that are more amenable to surgical resection,
      resulting in improved survival rates. The average 5-year survival rate for those
      who have undergone surgical resection is 68% (range, 22-73%). Better results are
      obtained with the smaller tumours (< 2 cm in diameter). Patients with chronic
      hepatitis B and C infection especially those who are > 45 years of age, who have
      concomitant cirrhosis or have a family history of HCC should be examined every 3
      6 months with periodic serum alpha-fetoprotein (AFP) measurements and abdominal
      ultrasound examinations. Abdominal ultrasound is useful in the detection of small
      tumours. While mass screening for HCC is not cost-effective in countries of low
      incidence of HCC, screening of high risk groups may be justified in countries
      with a high endemicity of HBV infection. Screening for HCC in Japan, Taiwan and
      China appears to yield better results than those in the West. Nonetheless,
      primary prevention with mass hepatitis B vaccination and blood donor screening
      for anti-HCV is expected to make a much greater impact in the control of HCC in
      the years to come.

PMID- 10967974
TI  - Dietary inquiries in public health practice.
AB  - Public health administrations are responsible for monitoring the availability and
      use of foods. The information required can be obtained cheaply and easily by
      asking schoolchildren about the foods they have consumed. When the mean weights
      of adults is low and the number of kinds of food in use is small, nutritional
      problems probably exist and must be investigated. The same indicators may also be
      useful in the identification of families affected by poverty.

PMID- 10967975
TI  - Bacterial hand infections: an analysis of cases presenting at the University
      Hospital, Kuala Lumpur.
AB  - A significant number of hand infections were found to occur in college students,
      a group not associated with manual labour. Diabetics did not have a significant
      delay in recognising the symptoms but have a significant longer period of
      hospitalisation. The right hand was predominantly involved especially the thumb,
      index finger and the thenar region. Staphylococcus aureus was the commonest
      infecting organism.

PMID- 10967976
TI  - Deaths in visceral leishmaniasis (Kala-azar) during treatment.
AB  - Twenty-seven out of five hundred and fifty three patients hospitalized for
      visceral leishmaniasis (Kala-azar) died during treatment with sodium antimony
      gluconate. Data from these patients were evaluated to find out the cause of
      death. Eight patients had associated diseases such as pulmonary tuberculosis (3),
      severe malnutrition (1), acute gastroenteritis (1), spleenic infarction (1),
      acute renal failure (1) and atrial septal defect (1) which could be attributed to
      death. Twelve patients developed spontaneous haemorrhages from nose, gums and
      gastrointestinal tract and died, despite of adequate supportive measures. Seven
      other patients who were improving slowly with antimony therapy died unexpectedly.
      Though, cause of death could be explained in some patients with associated
      disease conditions, it could not be explained in others as significant clinical
      manifestations, haematological, biochemical and electrocardiographic alterations
      were not evident prior to death. Our impression is that mortality in Kala-azar
      patients during standard antimonial therapy is more related to the drug rather
      than the disease process.

PMID- 10967977
TI  - Prevalence of hypertension among Chinese elderly and its relationship to
      behavioural and nutritional factors.
AB  - A cross-sectional study was carried out to determine the prevalence of
      hypertension in the Chinese elderly and to examine its relationship with various
      behavioural and nutritional risk factors. This study involved 243 Chinese aged 55
      years and older in 2 randomly selected Chinese Villages in Seberang Prai Tengah,
      Penang. The study included an interview, anthropometric assessment and blood
      pressure measurement. The prevalence of hypertension was 48.1% and out of this,
      65 (55.6%) were on anti-hypertensive treatment. There was a significant rise in
      the prevalence with age. Hypertension was found to be inversely related to per
      capita income and physical activity (p < 0.05). Hypertension was significantly
      more common in smokers than non-smokers. Alcohol intake in the elderly was low
      and not related to hypertension. Obesity was significantly associated with
      hypertension only among the elderly aged 55-64 years. The dietary intake of
      sodium, potassium and calcium did not differ significantly between the
      hypertensive and normotensive elderly.

PMID- 10967978
TI  - Changing prevalence of diabetes mellitus amongst rural Malays in Kuala Selangor
      over a 10-year period.
AB  - A cross-sectional study was carried out to determine the prevalence of diabetes
      mellitus and its relationship with age, physical activity, nutritional status and
      diet amongst rural Malays in Kuala Selangor. By simple random sampling 360
      subjects were selected for the study. Besides guided questionnaires, subjects
      also underwent a 2 hours post prandial (2HPP) test to determine the diabetic
      status as recommended by WHO. The crude prevalence of diabetes mellitus was 14.6%
      which increases with age. The prevalence of diabetes adjusted for age was 12.2%.
      Physical activity status seemed to be a significant risk factor for diabetes. A
      greater proportion of diabetics was obese and their mean fat intake was higher
      than normal subjects (p < 0.05). The prevalence of diabetes mellitus in this
      study was significantly higher compared with data from 1984 (3.9%), representing
      a marked increment of 212.8 per cent over a 10-year period.

PMID- 10967979
TI  - Diabetic control among NIDDM patients in urban and rural areas in Malaysia.
AB  - Sixty three and fifty nine non-insulin dependent diabetes mellitus (NIDDM)
      patients in rural (land resettlement scheme) and urban areas respectively were
      studied to determine factors associated with diabetic control. The anthropometric
      and metabolic data (HbA1 and fructosamine levels) were analysed. After adjusting
      for gender, age, body mass index (BMI) and food intake, the fructosamine level
      which correlates with short term diabetic control, was significantly lower among
      patients in urban areas compared to patients in rural areas (p < 0.05). However,
      for longer term diabetic control (HbA1 level) the difference was not
      statistically significant (p > 0.05). The socio-economic status, level of
      education, BMI and types of food did not correlate with diabetic control in
      either group of patients. More diabetes education is needed together with socio
      economic development and changes in lifestyles to enhance compliance towards
      health and dietary regimens and to achieve better metabolic control.

PMID- 10967980
TI  - Anaesthetic related maternal deaths in Malaysia--a review.
AB  - The anaesthetic hazards for the obstetric patient are well known. Based on
      results of the first two reports on the confidential enquiry into maternal deaths
      in Malaysia for 1991 and 1992, ten cases of anaesthetic related deaths were
      analysed. There were 3 in 1991 and 7 in 1992 accounting for 1.34% and 2.8% of
      maternal deaths respectively. It was estimated that the crude mortality rate for
      the obstetric patient was 11.4 per 100,000 operative deliveries or a four-fold
      risk compared to the general surgical patient. One case resulted from
      administration of intravenous sedation while the rest involved general
      anaesthesia, seven of which were done under emergency conditions. Inadequate
      airway management and ventilation in the perioperative period, including during
      interhospital transfer was the single most important factor causing the majority
      of these deaths. The use of regional anaesthesia for Caesarean sections is
      strongly advocated. Substandard care was also present in all cases. Other issues
      pertinent to improvement of obstetric anaesthetic services are also discussed
      which include the quality of anaesthetic manpower, upgrading of infrastructure,
      facilities and staffing of operating and recovery areas, the use of regional
      anaesthesia, expanding the role of the anaesthetist and the quality of the
      anaesthetic services in general.

PMID- 10967981
TI  - Fetal heart sound analysis: a preliminary evaluation.
AB  - The aim of this study, is to determine whether the fine characteristics of the
      fetal heart sounds could be used to identify intrauterine growth retarded
      fetuses. A preliminary evaluation, was conducted to compare these characteristics
      between intrauterine growth retarded fetuses and normal fetuses in the antenatal
      period after 36 weeks of gestation. Altogether, 7 IUGR fetuses were compared with
      12 normal fetuses. An instrument named the Fetal Frequency Phonocardiogram was
      designed for this purpose. When connected to a personal computer and with a
      software programme specially written, the fetal heart sound characteristics were
      analysed. After detailed analysis, there were 3 significant differences between
      IUGR and normal fetuses, all of which gave a p-value of < 0.01. The frequency of
      the first heart sound was significantly higher in the IUGR fetuses compared to
      normal fetuses. The ratio of the amplitude of the first heart sound over the
      second heart sound was higher in the IUGR group. Finally, the ratio of the time
      between the first and second heart sound over the cardiac cycle was shorter in
      the IUGR fetuses. Fetal heart sound analysis, may provide a simple non-invasive
      method of detecting and monitoring fetuses at risk in the antenatal period.

PMID- 10967982
TI  - Serum lipid & lipoprotein profiles of obese Chinese children.
AB  - The serum lipid and lipoprotein levels of 59 obese Chinese children with a mean
      age of 13.0 years and mean relative weight of 164.2% were analysed. Between 40%
      to 54% of these children had elevated lipid and lipoprotein levels and about 78%
      had reduced high density lipoprotein (HDL) level when compared to healthy
      American and Japanese children. The obese children also had higher mean levels of
      total cholesterol (TC) and lower HDL compared to male adults in the local
      population. Those with elevated TC had higher mean relative weight (170% vs 159%,
      p < 0.05). In view of the close association between hyperlipidaemia and
      atherosclerosis, obese children should be carefully screened and managed to
      prevent long term morbidity and mortality of coronary artery disease.

PMID- 10967983
TI  - Coronary stents in the management of coronary artery disease review of first 100
      stents.
AB  - This is a review of the first 100 coronary stents implanted for the indications
      of PTCA restenosis, acute or threatened closure and De Novo lesions. The success
      rates were high and complications rates were low. Subacute stent thrombosis rates
      were low and stenting for De Novo lesions in > 3.0 mm arteries provide the best
      short and long term results. Six months restenosis rate was low. Stent assisted
      high pressure balloon angioplasty is an important advance.

PMID- 10967984
TI  - A portal recording system for the assessment of patients with sleep apnoea
      syndrome.
AB  - The gold standard for the diagnosis and evaluation of sleep apnoea is overnight
      polysomnography. However, full polysomnography is an expensive and labour
      intensive procedure which requires the patient to sleep overnight in a hospital
      sleep laboratory. This paper describes the use of a commercial ambulatory
      microprocessor based system (Edentrace II) for the evaluation of fifteen patients
      aged 24 to 68 years with clinical features suggestive of sleep apnoea syndrome.
      With this portable recording system, sleep studies can be carried out unattended
      in a hospital ward and computer-assisted scoring of respiratory events can be
      performed.

PMID- 10967985
TI  - An audit on the assessment and management of acute bronchial asthma in the
      accident and emergency department of a district hospital.
AB  - A study was undertaken to determine the assessment and management of adult
      asthmatic patients presenting to the Accident and Emergency department. The
      records of 50 consecutive adult asthmatic patients presenting to A & E with acute
      bronchial asthma between June 1993 to April 1994 were reviewed. Patients were
      also interviewed on their subsequent visit to hospital. Observations and
      measurements used to assess the severity of asthma were recorded with variable
      frequency--cyanosis 8%, inability to speak 2%, chest auscultation 64%, heart rate
      10%, blood pressure 6%, respiratory rate 4%. The failure to record more objective
      measurements of severity of asthma and in particular extent of airflow
      obstruction is cause for concern. The drugs used to treat acute asthma in order
      of frequency were Beta agonists by nebuliser, 49 patients; intravenous
      aminophylline, 8 patients; and intravenous corticosteroids, 6 patients. 15
      patients were admitted to the medical ward. The decision to admit patients
      appeared to be due to a lack of symptomatic improvement after treatment. Of the
      35 patients who were discharged from A & E, 13 (37%) had an acute relapse within
      10 days. None of the patients on discharge from A & E were given a short course
      of oral steroids or were advised an increase in steroid inhaler therapy. There
      was therefore a gross underuse of corticosteroids.

PMID- 10967986
TI  - Gastro-oesophageal reflux in children with severe respiratory symptoms--clinical
      spectrum and management.
AB  - Respiratory symptoms in children may be associated with underlying gastro
      oesophageal reflux (GOR). We reviewed the case notes of 20 children who presented
      to us from June 1993 to June 1994 with respiratory symptoms and GOR. The patients
      consisted of 16 Malays, two Chinese and two Indians with equal number of males
      and females. Their age at diagnosis was less than one year in 17 patients. The
      earliest age at presentation was at the third day of life. All patients had major
      respiratory manifestations i.e. recurrent wheezing, recurrent cough and
      pneumonia. In addition, three patients had stridor and six patients had apparent
      life threatening episodes (ALTE). Fourteen patients required ventilation because
      of respiratory failure. Diagnosis of GOR was based on clinical grounds supported
      by barium oesophagogram in seven patients and ultrasound examination in 11
      patients. Eight patients were fundoplicated because of ALTE and recurrent severe
      bronchospasm. On follow up, 14 patients had hyperactive airways requiring inhaled
      bronchodilator and steroid therapy.

PMID- 10967987
TI  - Primary biliary cirrhosis--experience in University Hospital, Kuala Lumpur.
AB  - Primary biliary cirrhosis is an uncommon disease amongst Malaysians. Over a 12
      year period, between 1979 and 1991, only seven patients with clinical,
      biochemical and histologic evidence of primary biliary cirrhosis were identified
      in University Hospital Kuala Lumpur. All were Chinese females between the ages of
      30 to 55 years. The presenting complaint was pruritus in 5 patients. All except
      one patient was jaundiced when the diagnosis was made. These patients were
      followed up from 1 to 11 years. Three deaths were reported, one from massive
      hemetemesis and two from liver failure.

PMID- 10967988
TI  - Hearing loss in diving--a study amongst Navy divers.
AB  - Despite the commonly observed condition of middle and inner ear barotrauma among
      divers, there is little evidence of insidious and permanent development of
      sensorineural hearing loss associated with diving. An audiometric survey was
      performed on a group of 120 divers and 166 non divers from the Royal Malaysian
      Naval Base in Lumut, West Malaysia between July to December 1991. The results of
      this survey revealed that insidious development of high frequency sensorineural
      hearing loss may be associated with diving. At frequencies 4000, 6000 and 8000 Hz
      the divers had higher mean hearing levels than non divers and their hearing at
      those frequencies seemed to deteriorate faster. The etiology of this insidious
      hearing loss is multifactorial and may be related to inner ear barotrauma,
      decompression sickness or noise-induced deafness.

PMID- 10967990
TI  - Guidelines on management of adult asthma: a consensus statement of the Malaysian
      Thoracic Society.

PMID- 10967989
TI  - Early experience of video-assisted thoracoscopic surgery.
AB  - Consecutive 25 patients (M/F:18/7) underwent video-assisted thoracoscopic surgery
      (VATS) for various chest illnesses. These included nine cases of pneumothorax,
      three cases of pericardial effusion, three cases of pleural effusion, four cases
      of lung lesion requiring either incisional or excisional biopsy, two cases of
      empyema, one case of traumatic haemothorax, and three cases of mediastinal
      lesion. The mean age was 36.2 years (range 19-78 years). A total of forty-three
      procedures were performed. The mean durations of intrapleural chest-tube
      requirement and hospitalisation following VATS alone were 4.5 days (range: 0-13
      days) and 8.3 days (range: 2-25 days) respectively. No intraoperative
      complication and VATS procedure-related mortality reported. Apart from simple
      analgesics such as paracetamol or tramadolol, no opiate analgesia was given to
      patients undergoing only VATS. The results support that VATS is a safe and
      effective procedure in the management of pulmonary, mediastinal, pericardial and
      pleural diseases and the treatment of persistent and recurrent spontaneous
      pneumothorax.

PMID- 10967991
TI  - Serological evidence of schistosomiasis in the Malaysian police field force.
AB  - A total of 1131 Police Field Force personnel were screened serologically for
      schistosomiasis in Malaysia. A total of 150 (13.3%) were tested positive or
      borderline. Stool samples from 75 of these cases were however all negative for
      schistosome eggs. This survey suggests that Police Field Force personnel may be
      agents for propagating the schistosome life cycle in Malaysia.

PMID- 10967992
TI  - Radiation doses to patient's relatives following radioiodine therapy.
AB  - A total of 10 volunteers were monitored for radiation doses, whose spouses were
      given radio-iodine (131I) orally. Nine of the spouses were given radio-iodine for
      Graves' disease and one for thyroid carcinoma. It was found that the highest
      radiation dose received by the volunteer was only 13.5% of the annual dose limit
      for individual members of the public. Hence, patients treated with radio-iodine
      do not pose a significant radiation hazard to the public.

PMID- 10967993
TI  - Necrotizing fasciitis.
AB  - A 31-year-old Pakistani man was admitted to hospital after sustaining a Grade I
      compound fracture of the mid-shaft of the left tibia and fibula following a motor
      vehicle accident. He developed septicaemic shock, acute renal failure and Group A
      streptococcal necrotizing fasciitis of the left leg. The patient underwent an
      above knee amputation followed by disarticulation of the left hip with extensive
      debridement. He was treated with benzylpenicillin, vancomycin, inotropes and
      continuous haemodialysis and survived without further sequelae. Subsequently,
      skin grafting was done over the wound site. This case highlights the role of
      Group A streptococcus as a cause of this rare and life-threatening infection.

PMID- 10967995
TI  - Glibenclamide induced chronic cholestasis simulating primary biliary cirrhosis: a
      case report.
AB  - A 43-year-old lady with long standing non-insulin dependent diabetes mellitus on
      glibenclamide presented with cholestatic liver disease. Initially she was thought
      to have developed primary biliary cirrhosis (PBC). When she made a spontaneous
      recovery following the withdrawal of glibenclamide, it became obvious that the
      patient had been suffering from drug-induced chronic cholestasis (DICC). The
      subtle differences between PBC and DICC are highlighted.

PMID- 10967994
TI  - A report of the first three cases of diffuse panbronchiolitis in Malaysia.
AB  - Three cases of diffuse panbronchiolitis (DPB) occurring in two Malaysian Chinese
      patients and one Malay patient are reported. They had similar clinical,
      radiological and physiological features which are characteristic of DPB. The
      diagnosis in one of the cases was confirmed histologically by transbronchial lung
      biopsy. These could be the first three cases identified in Malaysia.

PMID- 10967996
TI  - Road traffic accidents in patients with obstructive sleep apnoea.
AB  - Three patients involved in road traffic accidents were suspected to have
      obstructive sleep apnoea (OSA). Two of them fell asleep while riding motorcycles
      and one patient fell asleep behind the wheel of a truck causing it to overturn.
      The diagnosis of OSA in each case was suspected based on a history of loud
      snoring, restless sleep, and excessive daytime somnolence and was confirmed by
      sleep studies.

PMID- 10967997
TI  - Concordant childhood acute lymphoblastic leukemia in monozygotic twins.
AB  - Two 4-year-old monozygotic Chinese, female twins developed concordant childhood
      acute lymphoblastic leukemia (ALL) within an interval of about 2 weeks. Based on
      morphology and cytochemistry findings of the bone marrow blast cells, a diagnosis
      of ALL, L1 was made. Immunophenotyping showed the blast cells of both twins
      expressed similar antigens, i.e. HLA-DR, CD10, CD13, CD19, CD22 and CD34.
      Identical blood group, same HLA (human leucocyte antigen) genotype, sex and
      similar appearance suggest that the twins are monozygotic. Since the bone marrow
      leukemic cells of both twins were identical in morphology and expressed the same
      antigens with almost similar percentages of positivity, it is likely that the
      blast cells were derived from the same single clone. Based on the single clone
      hypothesis, the leukemogenic event must have arisen in utero in one twin and the
      cells from the abnormal clone then spread to the other twin via shared placental
      anastomoses.

PMID- 10967998
TI  - Spontaneous rupture of renal angiomyolipoma presenting as acute abdomen.
AB  - Five cases of renal angiomyolipoma which underwent spontaneous rupture are
      described. These patients presented as an "acute abdomen" for which the diagnosis
      was not initially apparent. A high index of suspicion is required to make the
      diagnosis even with modern imaging techniques. The treatment of these tumours is
      discussed.

PMID- 10967999
TI  - Spinal dural arteriovenous malformation: a cause of myelopathy.
AB  - Spinal vascular malformation is an uncommon but potentially treatable cause of
      myelopathy. We describe two cases of angiographically proven spinal vascular
      malformation in Malaysia. The first case is a 47-year-old man who had a
      progressive myelopathy and the second a 60-year-old man with intermittent attacks
      of transient paraparesis leading to paraplegia. As the clinical presentation of
      spinal vascular malformation is variable, it should be considered as a cause of
      patients with myelopathy.

PMID- 10968000
TI  - Psychiatric presentation of Huntington's disease in a Malaysian family.
AB  - A 32-year-old Chinese lady presented to the Psychiatric Clinic with a history of
      change in personality for 2 years and abnormal movements for a year. After
      thorough investigations and observation a diagnosis of Huntington's Disease was
      made. Her elder brother was traced and found to have Huntington's Disease as
      well. He had a long standing history of antisocial behaviour and substance abuse
      long before the onset of the choreiform movements. Her younger brother also has
      choreiform movements for the last 2 years and had recent change in personality.
      Their mother also had abnormal movements and was recorded to be depressed and
      attempted suicide. The maternal grandfather had a mental illness and was warded
      at a mental institution till his death in 1942. Psychiatric presentation of
      Huntington's Disease in this Malaysian family is prominent and preceded the
      characteristic movements in the present generation.

PMID- 10968001
TI  - Bladder outflow obstruction masquerading as pelviureteric junction (PUJ)
      obstruction.
AB  - We report a case of bladder outflow obstruction presenting with upper tract
      dilatation mistaken initially as pelviureteric junction (PUJ) obstruction. The
      lower tract obstruction ought to be dealt with first before upper tract
      obstruction is assessed because the renal pelvic pressure is significantly
      affected by vesical filling and high bladder pressure.

PMID- 10968002
TI  - A case of traumatic cholecystectomy.

PMID- 10968003
TI  - "Chap Kaki Tiga" a possible cause of upper gastrointestinal haemorrhage.

PMID- 10968004
TI  - Breast cancer 100 years on--what we have learnt!

PMID- 10968006
TI  - A short history of the Medical Journal of Malaysia.

PMID- 10968005
TI  - Advances in health in Malaysia.

PMID- 10968007
TI  - Development of urology and nephrology at General Hospital, Kuala Lumpur from 1962
      1974.

PMID- 10968008
TI  - Medical progress in the Straits Settlements--an editorial note.

PMID- 10968009
TI  - Medicine in Malaysia: cardiology.

PMID- 10968010
TI  - Medicine in Malaysia: nephrology.

PMID- 10968011
TI  - Medicine in Malaysia: endocrinology.

PMID- 10968012
TI  - Medicine in Malaysia: dermatology.

PMID- 10968013
TI  - Medicine in Malaysia: radiotherapy and oncology.

PMID- 10968014
TI  - Medicine in Malaysia: sexually transmitted diseases and AIDS.

PMID- 10968015
TI  - Medicine in Malaysia: haematology.

PMID- 10968016
TI  - Medicine in Malaysia: pathology.

PMID- 10968017
TI  - Medicine in Malaysia: microbiology and infectious diseases.

PMID- 10968018
TI  - Medicine in Malaysia: parasitic diseases.

PMID- 10968019
TI  - Medicine in Malaysia: paediatrics.

PMID- 10968020
TI  - Medicine in Malaysia: psychiatry.

PMID- 10968021
TI  - Medicine in Malaysia: general surgery.

PMID- 10968022
TI  - Medicine in Malaysia: orthopaedic surgery.

PMID- 10968023
TI  - Medicine in Malaysia: ophthalmology.

PMID- 10968024
TI  - Medicine in Malaysia: anaesthesiology.

PMID- 10968025
TI  - Menopause and hormone replacement therapy. Facts and misconceptions.

PMID- 10968026
TI  - Practice patterns of some gynaecologists in Malaysia with regards to prophylactic
      oophorectomy and hormone replacement therapy.
AB  - This study aimed to look at the prevailing practice patterns of gynaecologists
      with regards to prophylactic oophorectomy and usage of hormone replacement
      therapy. Questionnaires were sent to the first 200 gynaecologists listed in the
      membership list of the Obstetrical and Gynaecological Society of Malaysia. The
      response rate was 30%. The results showed that most gynaecologists would perform
      prophylactic oophorectomy after the age of 49 years. The result was equivocal for
      the ages between 45 to 49 years. Of those who retained the ovaries at the age of
      45 to the menopause, 55% did so because the ovaries were still functional. Almost
      all gynaecologists would prescribe hormone replacement therapy (HRT) after
      oophorectomy and the most commonly prescribed form was the oral type. Thirty-five
      per cent of gynaecologists claimed that more than 80% of their patients were
      compliant to HRT. The reasons perceived for the poor compliance were mainly poor
      knowledge and misconception.

PMID- 10968027
TI  - Outcome of vaginal hysterectomy for the undescended and enlarged uterus--a
      preliminary report.
AB  - This is a retrospective observational study of outcome of 11 cases of vaginal
      hysterectomy for undescended and enlarged uterus carried in University Hospital,
      Kuala Lumpur. The cases included relative contraindications such as 14 weeks size
      fibroids, severe obesity, previous Caesarean section and nulliparity. All the
      eight patients agreeable for prophylactic bilateral salpingoophorectomy had their
      ovaries removed. Operative time ranged from 1 hr 20 min to 2 hr 15 min. All
      patients were sent home within 48 hours of the operation. The excellent outcome
      of our initial experience highlights the known advantages of vaginal hysterectomy
      for undescended and enlarged uterus.

PMID- 10968028
TI  - Anaesthetic management of conjoined twins: experience with six sets of twins.
AB  - Anaesthesia for the separation of conjoined twins requires a well-prepared,
      multidisciplinary team. Each patient for surgery is different and the extent of
      organ sharing and coexisting anomalies must be determined before surgery so that
      problems can be anticipated. We report our experience of the anaesthetic
      management for the separation of six sets of conjoined twins. Anaesthesia and
      surgery were prolonged, massive blood loss and transfusion, hypothermia,
      electrolyte imbalance and infection being the main perioperative problems
      encountered.

PMID- 10968029
TI  - Differences in public and private health services in a rural district of
      Malaysia.
AB  - A cross-sectional study, comparing the nature of services in 15 private clinics
      and 6 public health facilities, was undertaken in a rural district of Malaysia.
      Semi-structured interviews and observations using check-lists were employed.
      Public health facilities were run by younger doctors (mean age = 31.1 years),
      supported mostly by trained staff. The private clinics were run by older doctors
      (mean age = 41.2 years) who had served the district for much longer (8.9 years vs
      1.5 years) but were supported by less well trained staff. The curative services
      were the main strength of the private clinics but their provision of preventive
      care was less comprehensive and of inferior quality. Private clinics were
      inclined to provide more expensive diagnostic services than the public
      facilities. 'Short hours' private clinics had very restricted opening hours and
      offered limited range of services.

PMID- 10968030
TI  - Mortality in Malaysians with systemic lupus erythematosus.
AB  - One hundred and two patients attending the systemic lupus erythematosus (SLE)
      clinic of the Department of Medicine, Universiti Kebangsaan Malaysia, were
      studied retrospectively to determine their survival rates and causes of death.
      There were 21 deaths. The 1, 5, and 10 year survival rates were 93%, 86% and 70%
      respectively. There was a bimodal pattern of mortality with more patients dying
      in the first 2 years or after 5 years of disease. Infection was the direct cause
      of death in 52% and contributed to a further 19% of deaths. Patients with lupus
      nephritis had a higher relative risk (RR) of death (RR = 4.34, p < 0.02) although
      there was no significant increase in risk with any particular histological type
      on biopsy. Cerebral lupus (RR = 3.08, p < 0.001) and methylprednisolone treatment
      (RR = 6.24, p < 0.001) were also associated with increased risk of death.
      Increased awareness of infection and earlier use of antibiotic therapy may
      improve survival of patients suffering from SLE.

PMID- 10968031
TI  - Management of gastroschisis in a peripheral hospital setting.
AB  - Ten patients (5 males and 5 females) with gastroschisis were treated in Alor
      Setar Hospital from January 1989 to December 1993. Two patients had associated
      congenital anomalies. Primary closure was possible in 9 patient while the other
      patient had stage closure. All patients received prophylactic antibiotics, 9
      patients were ventilated electively in the post-operative period and 7 patients
      received parenteral nutrition. There were 9 survivors. Complications especially
      wound infection and breakdown were seen in 7 patients. The average hospital stay
      was 36 days.

PMID- 10968032
TI  - Risk factors for retinopathy in diabetes mellitus in Kelantan, Malaysia.
AB  - Few attempts have been made to determine the risk factors for diabetic
      retinopathy which is a major cause of visual impairment and blindness. One
      hundred and forty patients of diabetes mellitus were studied to determine the
      prevalence and types of retinopathy, and its relation to various risk factors.
      Nearly half (48.6%) of the patients suffered from retinopathy. The significant
      associated risk factors were long duration of diabetes, proteinuria and elevated
      serum creatinine level. However, there was no significant association between the
      prevalence of retinopathy and high levels of serum cholesterol, C-peptide levels,
      associated hypertension, and glycaemic control of diabetes mellitus. An effective
      screening programme for detection of retinopathy in the patients of diabetes as a
      regular practice is encouraged.

PMID- 10968033
TI  - Acceptability of epidural analgesia for pain relief during labour among
      Kelantanese women.
AB  - Three hundred and five primigravid women were interviewed at term to assess the
      acceptability of epidural during labour, and reasons for the decisions. Data was
      collected on a prestructured proforma which consisted of background information,
      socio-economic status, knowledge about epidural analgesia, source of information
      and reasons for choice. Of the 305 patients only 17.3% were willing to receive
      epidural analgesia. This group consisted of 56.6% non-Malay women. Those employed
      in professional or skilled jobs (56.6%) also readily consented for epidural.
      Nearly half the women willing for epidural had received college (tertiary)
      education (43.3%) and more than a quarter (26.4%) were over 30 years of age. The
      majority of those who were unwilling had no prior knowledge about the procedure,
      and refused either out of fear, ignorance, resistance from husbands, on religious
      grounds or following poor feedback from friends. In order to advocate epidural
      analgesia, knowledge has to be targeted to the relatively less educated,
      unemployed women, mainly through the media or personally in the antenatal clinic
      by doctors and nurses. Services have to be improved as substandard analgesia may
      send out wrong messages and actually do more harm than good.

PMID- 10968034
TI  - The role of ductography in patients with nipple discharge.
AB  - The main objective of this study is to illustrate the role of ductography in the
      management of nipple discharge. Thirty-six patients had ductography for the
      investigation of blood-stained or serous nipple discharge. The ductogram findings
      were reviewed. Ductography showed an intraductal lesion in 13 patients, duct
      ectasia in 16 and normal ducts in 7. Fourteen patients had surgery. Eight had
      preoperative ductography using a mixture of methylene blue and contrast media.
      Histology revealed 5 cases of duct papilloma, 2 cases of epithelial hyperplasia,
      4 cases of fibrocystic change and 3 cases of duct ectasia. Twenty had follow-up
      without surgery and of these, the nipple discharge ceased in 11 patients. Two
      patients did not come for follow-up. Ductography has a significant role in the
      management of nipple discharge. Firstly, surgery might be averted in patients
      with normal ducts or duct ectasia on ductography. Secondly, intraductal methylene
      blue will demonstrate the abnormal ductal system to the surgeon and allow for a
      less radical surgery.

PMID- 10968035
TI  - Parental reactions to febrile seizures in Malaysian children.
AB  - The reactions of 117 parents to the febrile seizure experienced by their
      children; and their fears and worries were investigated. A standard questionnaire
      was used and clinical information was abstracted from the notes. In 88.9% of the
      cases, the adult present at the seizure was one of the parents usually the
      mother. Most of the parents (66.7%) did tepid sponging to bring the fever down
      but a third tried to open the clenched teeth of the child. The adults present
      placed the child supine in 62.9%, on the side in 9.5% and prone in 6.0%. Over
      half of the parents brought the child to a private clinic first before bringing
      to hospital. A fifth of the children were given antipyretics by the parent or the
      doctor and an anticonvulsant was given in 7.7% of cases. Interestingly, in 12% of
      children traditional treatment was given for the seizure. Three quarters of the
      parents knew that the febrile seizure was caused by high fever (which we have
      taken as the correct knowledge of febrile seizure). However "ghosts" and
      "spirits" were blamed as the cause of the seizure by 7% of parents. Factors
      significantly associated with correct knowledge were higher parental education
      and higher family income. The most common fear expressed was that the child might
      be dead or might die from the seizure (70.9%). Fear of death was associated with
      low paternal education. We concluded that the majority of our parents had reacted
      appropriately to a febrile seizure and their knowledge of the cause of febrile
      seizure was generally correct. Their fears and worries were similar to those
      elsewhere. However, traditional beliefs and practices may have to be taken into
      consideration during counselling.

PMID- 10968036
TI  - Outcome of 80 cases of external cephalic version.
AB  - This is a prospective observational study of the outcome of 80 cases of external
      cephalic version (ECV) at term using terbutaline infusion. There were 55
      primiparas and 25 multiparas. The successful ECV rate was 44% and 85%
      respectively. The majority (82%) of the patients with successful ECV delivered
      vaginally. Parity and type of breech were the two significant factors in the
      success of the procedure.

PMID- 10968037
TI  - Prevalence of giardiasis among Malaysian primary school children.
AB  - Giardiasis, a gastrointestinal disease caused by Giardia intestinalis is endemic
      in Malaysia. The prevalence rate has been reported to range from 1.4% to 11.1%.
      The present study was undertaken between 1992-1994 in three health districts in
      three states viz. Pahang, Negeri Sembilan and Selangor. Seven thousand five
      hundred and fifty seven (7557) primary school children between the ages of 6-12
      years from the lower socio-economic groups were screened. The prevalence was
      0.21%. The study suggests that improved water supply, toilet facilities and
      sanitation have lowered the prevalence of a waterborne disease in the areas
      surveyed.

PMID- 10968038
TI  - Extra pelvic endometriosis and catamenial pneumothorax.
AB  - Extra pelvic endometriosis is rare and its presentation is varied. A case of
      pulmonary and umbilical endometriosis which presented as catamenial pneumothorax
      is presented. Due to poor response to medical treatment, a total abdominal
      hysterectomy and bilateral salpingo-oophorectomy was done to relieve the patient
      of her recurrent symptoms.

PMID- 10968039
TI  - The first frozen embryo donation pregnancy for hypergonadotrophic hypogonadism in
      Singapore--hormonal profile and obstetric outcome.
AB  - This is the first report in South East Asia of a singleton frozen embryo donation
      pregnancy for hypergonadotrophic hypogonadism. The hormonal profile was compared
      with that of a control group of normal uncomplicated singleton pregnancies in
      Singapore. The plasma beta hCG levels were lower compared to those of our normal
      uncomplicated singleton pregnancies at 2 to 3 weeks after the embryo transfer but
      became comparable at 4 to 5 weeks after embryo transfer. The successful vaginal
      delivery and the obstetric complications developed in this case are discussed.

PMID- 10968040
TI  - Co-existing tubal ectopic pregnancy and appendicitis--a case report.
AB  - Appendicitis in pregnancy has a well documented high morbidity due to the
      difficulty in diagnosis. However, synchronous ectopic pregnancy and appendicitis
      is a rare event. This report describes the case of a 22-year-old lady of
      Bangladeshi origin who presented with both these conditions. The importance of
      prompt diagnosis and early surgical intervention, the inherent difficulties in
      diagnosis and the possible interrelated aetiological factors are discussed.

PMID- 10968041
TI  - Supernumerary chromosomes in mosaic Turner syndrome.
AB  - The finding of a supernumerary or marker chromosome in a karyotype poses
      difficulty in genetic counselling. The true incidence and significance of this
      chromosomal aberration is unknown in Malaysia. We report two patients who
      presented with supernumerary chromosomes in mosaic Turner syndrome.

PMID- 10968042
TI  - Topical chloramphenicol/gentamicin in the empirical treatment of acute
      conjunctivitis--is it rational?

PMID- 10968043
TI  - The effectiveness of permethrin-impregnated bed nets for malaria control in Kg.
      Ganoh, an Orang Asli area of Rompin District, Pahang.

PMID- 10968044
TI  - Sepsis.

PMID- 10968045
TI  - Antibiotic prophylaxis in surgery.

PMID- 10968046
TI  - Single-dose antibiotic prophylaxis in women undergoing elective caesarean
      section.
AB  - This prospective, randomised, controlled trial was performed to evaluate the
      effectiveness of single-dose antibiotic prophylaxis in decreasing the infectious
      morbidity following elective caesarean section. Two hundred women undergoing
      elective caesarean section were randomly assigned to receive either 1.2 g of
      Augmentin intravenously, or no treatment, just before the start of their
      caesarean section. The two groups of women were comparable in terms of patient
      characteristics and operation variables. The overall postoperative morbidity rate
      was 19% in the Augmentin treated group versus 38% in the group that received no
      prophylaxis (p < 0.01). The incidence of wound sepsis was 3% in the Augmentin
      group versus 13% in the control group (p < 0.01). The incidence of febrile
      morbidity with no identifiable cause was 8% in the Augmentin group versus 18% in
      the control group (p < 0.05). The duration of hospital stay was significantly
      shorter in the Augmentin group (p < 0.05). A single-dose of prophylactic
      Augmentin significantly reduced the postoperative morbidity and duration of
      hospital stay in women who underwent elective caesarean sections.

PMID- 10968047
TI  - The occurrence of autoantibodies in sera of healthy pregnant women.
AB  - Autoantibodies have been known to be detected during pregnancy. The occurrence of
      autoantibodies during pregnancy was studied in a group of 146 healthy pregnant
      women from Jan-March 1995. Serum samples were tested for antinuclear (ANA), anti
      ds DNA, anti-mitochondrial, anti-smooth muscle and anti-parietal cell antibodies
      employing the technique of indirect immunofluorescence. Sera from 66 non-pregnant
      women were used as controls. Among the pregnant group, 2 (1.4%) were found to
      have ANA positivity in comparison to none in the control group. This difference
      was found to be not statistically significant. Only 1 (0.7%) was positive for
      anti-mitochondrial antibody in the pregnant group compared to one in the control
      group (p > 0.05). However, anti-ds DNA, anti-smooth muscle and anti-parietal cell
      antibodies were not detected in both groups. All those positive for
      autoantibodies were in their 2nd trimester. When these cases were followed-up at
      the end of their pregnancy, none had complicated pregnancies nor infant
      abnormalities. Our findings suggest that (a) the occurrence of autoantibodies in
      pregnant women was not significantly different from non-pregnant controls and
      that (b) maternal autoantibodies did not appear to cause complications during
      pregnancy or infant morbidity.

PMID- 10968048
TI  - A study of perforating eye injuries at the Ophthalmology Department, National
      University of Malaysia.
AB  - One hundred and sixty seven (167) perforating eye injuries involving 159 patients
      were analyzed in a retrospective study over a three-year period. The degree of
      blindness and their associated factors were determined. Most patients were in the
      first three decades of life and were males. One hundred and seven (64%) eyes had
      vision of 3/60 or worse at initial assessment. Of these only 45% of eyes had
      improved vision to 6/36 or better at six months of follow-up. Fifty-five per cent
      of eyes were blind. The only significant associated factor identified was the
      extent of injury. Age, time interval and mechanism of injury were not significant
      factors.

PMID- 10968050
TI  - Adult allogeneic bone marrow transplantation: initial experience in the
      University Hospital, Kuala Lumpur.
AB  - Prior to 1993, bone marrow transplantation for adult patients was not available
      in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia
      when the first transplant was conducted at the University Hospital, Kuala Lumpur
      on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been
      conducted at the University Hospital. Five patients had acute myeloid leukaemia
      in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic
      leukaemia in first partial remission. The age range of patients at the time of
      transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully
      and the survival for the first 100 days post-transplant is 90%. One patient
      demonstrated haematological relapse post-transplant but achieved remission with
      donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first
      100 days. Locally available adult allogeneic bone marrow transplantation is safe,
      affordable and has comparable results with reputable overseas transplant centres.

PMID- 10968051
TI  - Experience of radioactive needle implants in the Institute of Radiotherapy
      Hospital Kuala Lumpur.
AB  - This retrospective study of radioactive needle implants at the Institute of
      Radiotherapy and Oncology, Kuala Lumpur Hospital serves as an audit of our
      practice as well as a demonstration of the usefulness of this technique of
      brachytherapy. A variety of tumour sites were implanted, of which over two-thirds
      involved the tongue and buccal mucosa. Although most of the implants were carried
      out with radical intent, one-tenth of these implants were performed for
      palliation. Radiotherapy techniques employed are described. The crude survival
      ranged from 1 month to 109 months while the disease free interval ranged from 0
      months to 102 months.

PMID- 10968049
TI  - The outcome of trabeculectomy for primary glaucoma in adult patients in UKM.
AB  - A clinical audit was conducted for a 4-year period at the Universiti Kebangsaan
      Malaysia (UKM) Ophthalmology Department in which 61 eyes of adult patients with
      primary glaucoma underwent trabeculectomies without antimetabolites. At a 2-year
      follow-up duration, successful trabeculectomies as defined by intraocular
      pressure below 20 mm Hg without additional glaucoma medication were 62% for
      primary open-angle glaucoma, 48% for primary acute angle-closure glaucoma and 43%
      for chronic angle-closure glaucoma. 50.8% of eyes were without complications
      while 49.2% had complications. Shallow anterior chamber (22.9%) and hyphaema
      (19.7%) were the two commonest complications.

PMID- 10968052
TI  - Serum lipids and their relationship with other coronary risk factors in healthy
      subjects in a city clinic.
AB  - Over a thousand subjects who visited a city private medical clinic for health
      screening and advice were examined for their lipid profile and other
      cardiovascular risk factors. The mean TC, TG, LDL-C and HDL-C were 5.43, 1.45,
      3.61 and 1.15 mmol/l. Their derived ratios viz, TC:HDL-C and LDL:HDL-C were 5.11
      and 3.43 respectively. The prevalence of hyperlipidaemia was moderately high. Of
      the subjects studied 58.5% had elevated serum cholesterol, 14.8% had raised
      triglycerides, 64.9% had raised LDL-C and 20.8% had low HDL-C. Male subjects
      generally showed higher mean values and abnormality frequency in TC, TG, LDL-C,
      TC:HDL-C and LDL:HDL-C as compared to female subjects. Although significant
      ethnic differences were not detected for certain lipid parameters (e.g. TC, TG
      and HDL-C), the Indians appeared to have higher mean lipid values (except HDL-C),
      and higher percentage abnormality for all the lipid parameters as compared to the
      Chinese and the Malays. In correlation studies, the following lipid parameters:-
      TC versus TG, LDL-C, TC:HDL-C; TG versus TC:HDL-C and LDL:HDL-C; LDL-C versus
      TC:HDL-C and LDL:HDL-C; were positively correlated. On the other hand, TC versus
      HDL-C, TG versus HDL-C, LDL-C and HDL-C, and HDL-C versus TC:HDL-C and LDL:HDL-C
      were negatively correlated. The coronary risk factors which generally showed
      positive correlations with lipid parameters were BMI and blood pressure. Positive
      correlations were also recorded between fasting blood glucose and TG; uric acid
      with TG, TC:HDL-C and LDL:HDL-C. In contrast, risk factors of negative
      correlations were observed between HDL-C and the coronary risk factors of BMI,
      diastolic blood pressure and uric acid. Smoking showed raised per cent lipid
      abnormality for TG, HDL-C, TC:HDL-C and LDL:HDL-C. Alcohol consumption also
      increased the mean level and abnormality frequency for TG. The implication of
      this investigation is discussed.

PMID- 10968053
TI  - A Malaysian Well Person's Clinic--review of patients seen between April and
      December 1995.
AB  - The Well Man & Well Woman's Clinic in Ipoh Hospital provides screening for
      coronary risk factors and early detection of cancer. This retrospective review of
      1095 patients screened between April and December 1995 showed 48% had one or more
      coronary risk factors--1 risk (29%), 2 risks (14%), 3 or more risks (5%).
      Modifiable risks included hypertension (10%), obesity (9%), diabetes mellitus
      (8%) and smoking (7%). Sixteen abnormal Papanicolaou smears and six cancers
      (three cervical, two breast and one ovarian) were detected. Public response was
      good. There is a need for clinics offering comprehensive screening in Malaysian
      primary health care.

PMID- 10968054
TI  - Childhood epilepsy: what parents know, believe and do.
AB  - This was a descriptive study to assess parents' knowledge of epilepsy in their
      children at the Klinik Pakar Pediatrik in Universiti Kebangsaan Malaysia from
      1.1.93-31.6.93. Factors that influence the level of knowledge were examined. Our
      hypothesis was that the level of knowledge was low and level of education and
      social factors were important. Fifty consecutive parents were interviewed during
      the clinic appointments. The questionnaire consisted of 25 questions which had
      been used in a survey on epilepsy in Australia. In order to cater for the local
      population the questions were modified by adding new questions pertaining to
      local situation. The results showed that 90% (45/50) of parents were unaware of
      the type of epilepsy their children were suffering from. 50% (25/50) of parents
      knew the underlying cause of epilepsy of which 32% (8/25) attributed it to brain
      disease, 8% (2/25) to birth defects and 10% (3/25) to fever. Factors such as
      duration of epilepsy, parental education and racial differences between Malay and
      other races (Chinese, Indians) did not reach any statistical significance (p >
      0.05). 80% of patients (30/50) were on monotherapy. However, 90% (45/50) of
      parents were unaware of their children's medications. 82% of parents (31/50) knew
      that the anti-convulsants would only control their children's convulsions. Only
      10% (8/50) of parents knew the acute management of seizures. Wrong practices such
      as inserting spoons (5/50) or massaging their limbs (17/50) during an acute
      attack were still common. 70% of parents (35/50) attended the follow-up clinics
      hoping that their children's epilepsy would be cured. Parents with low economic
      status and of children with duration of epilepsy of less than five years had been
      coming to the clinic regularly. (p = 0.01 and p = 0.02 respectively). In
      conclusion, the overall knowledge of these parents was poor. In order to improve
      the management of epilepsy, it is necessary to educate parents with reading
      materials and effective educational packages.

PMID- 10968055
TI  - Glucose: a reevaluation of its intraoperative use in paediatric surgery.
AB  - Blood glucose concentration was measured in 100 children immediately before and
      during surgery. These children were randomly assigned to receive either lactated
      Ringer's (LR) solution or 5% dextrose in lactated Ringer's (5%D/LR)
      intraoperatively as maintenance and replacement fluids. Blood samples were taken
      immediately after induction of anaesthesia and at 1/2, 1, 1.5, 2 and subsequent
      hours. Blood glucose concentration was assayed by a reflectance meter. None of
      the patients was noted to be hypoglycaemic pre- and intraoperatively.
      Intraoperative blood glucose concentration increased significantly (p < 0.05)
      from preoperative levels for both groups of children but the increase in those
      that received 5%D/LR was significantly greater (p < 0.05) than those who received
      LR. The number of children who were hyperglycaemic during surgery was also
      greater in those who received 5% dextrose in lactated Ringer's as their
      intraoperative fluid. These data suggest that lactated Ringer's alone is a safe
      and appropriate fluid for intraoperative fluid therapy in children.

PMID- 10968056
TI  - Oxygen consumption--a comparison between calculation by Fick's principle and
      measurement by indirect calorimetry.
AB  - Oxygen consumption values calculated by Fick's principle (cVO2) were compared to
      simultaneously obtained values measured by indirect calorimetry (mVO2) in two
      groups of patients; post-coronary artery bypass graft (post-CABG) and septic
      shock. In both groups of patients, oxygen consumption values derived using
      indirect calorimetry were higher than that from Fick's principle. Whilst the bias
      obtained between the two methods of measurement were of acceptable amount
      clinically, the limits of agreement were wide: -57 to 51 ml.min-1.m-2 in the post
      CABG group and -101 to 67 ml.min-1.m-2 in the group of septic patients;
      indicating that significant differences exist between paired individual values
      such that cVO2 and mVO2 were not interchangeable in this study.

PMID- 10968057
TI  - Career preferences of male and female medical students in Malaysia.
AB  - A survey of career choices were conducted for three batches of final year medical
      students at Universiti Sains Malaysia. A total of 241 students responded, giving
      a response rate of 76%, with 107 males (44.4%) and 134 females (55.6%). Surgery
      ranked highest among the male students while obstetrics and gynaecology ranked
      highest among female students. Internal medicine was the second choice for both
      males and females. Among the other specialties, the male students shows preferred
      Hospital Administration and Radiology while female students preferred Community
      Medicine, Psychiatry and Pathology. Both male and female students chose to be a
      clinical consultant in a general hospital as the first choice. They prefer to
      work in or near their hometowns.

PMID- 10968058
TI  - Endotracheal tube ignition during CO2 laser surgery of the larynx.
AB  - We report a case of endotracheal tube fire occurring during CO2 laser surgery of
      the larynx. The ignition of an endotracheal tube was thought to be caused by
      laser penetration of an unprotected portion of the tube during resection of vocal
      cord tumour. Fire hazard is inevitable when a laser is used in the path of
      combustible gases and in the presence of flammable objects. We discuss the
      methods of prevention that were used.

PMID- 10968059
TI  - Pulmonary involvement by Hodgkin's disease mimicking pneumonia.
AB  - A 24-year-old man who was initially thought to have nocardiosis of his
      mediastinal lymph node which progressed to involve his right lung, had to undergo
      a right pneumonectomy when he failed to respond to treatment with sulphadiazine.
      Histology of the right lung specimen and a subsequent axillary lymph node biopsy
      revealed that he actually had lymphocyte-depleted Hodgkin's disease.

PMID- 10968060
TI  - Primary non-Hodgkin's lymphoma of the cranial vault mimicking a meningioma: a
      case report.
AB  - Primary non-Hodgkin's lymphoma of the brain is rare. Majority of the lesions are
      intraaxial, multicentric and involve the leptomeninges. We report a case of
      malignant primary non-Hodgkin's lymphoma arising from the cranial vault. Computed
      tomography of the brain showed an extraaxial lesion in the right parietal region
      mimicking a meningioma.

PMID- 10968061
TI  - Severe combined immunodeficiency in a Malaysian child.
AB  - A 3-month-old Malay male infant presented with multiple infections (candidiasis,
      Pseudomonas aeruginosa, Cytomegalovirus), persistent pneumonia, intractable
      diarrhoea and failure to thrive. There was lymphopaenia affecting both T and B
      subsets. He developed Graft versus Host disease weeks following transfusion with
      non irradiated blood. In spite of aggressive microbicidal and supportive therapy
      including regular immunoglobulin infusions, the child succumbed to infection
      before a bone marrow transplant could be instituted.

PMID- 10968062
TI  - Tuberculous infection.
AB  - A female patient presenting with post-prandial epigastric pain and weight loss
      was diagnosed to have oesophageal tuberculosis by endoscopic biopsy. She
      responded well to standard anti-tuberculosis treatment.

PMID- 10968063
TI  - Successful closure of a recto-prostatic fistula.
AB  - Recto-prostatic fistula is a rare complication of prostatic surgery, occurring
      usually because surgical planes are not appreciated. We describe a combined
      abdomino-perineal approach for the repair of a large recto-prostatic fistula with
      the interposition of omentum and gracilis without formally closing the fistula in
      layers.

PMID- 10968064
TI  - Ambulatory carbon dioxide laser haemorrhoidectomy without disability.

PMID- 10968065
TI  - Psychiatry for the general practitioner.

PMID- 10968066
TI  - Viruses and cancer.

PMID- 10968067
TI  - Human papillomavirus DNA and virus-encoded antigens in cervical carcinoma.
AB  - The present study was undertaken to evaluate the prevalence of HPV in formalin
      fixed, paraffin-embedded cervical carcinoma tissues using PCR followed by non
      radioactive Southern hybridization with type-specific oligonucleotides for HPV 16
      and 18. In addition, the tissue sections were immunohistochemically screened with
      two monoclonal antibodies, for expression of HPV 16 L1 and HPV 18 E6 proteins. A
      total of 57 of 60 cervical carcinomas (95.0%) were found with HPV using both
      techniques. HPV 16 and HPV 18 were present in equal proportions. Results of both
      DNA hybridization and immunohistochemistry were in agreement for the majority of
      the cases. HPV 16 and 18 DNA and virus-encoded antigens, L1 and E6 were found
      highly prevalent in these cervical carcinomas. Due to the high prevalence of HPV
      with cervical carcinoma in Malaysia, the implementation of routine diagnosis for
      the virus in cervical biopsies would be clinically useful.

PMID- 10968068
TI  - Adjuvant chemotherapy for colorectal cancer: a Malaysian experience.
AB  - This study aims to evaluate the practice of adjuvant chemotherapy in colorectal
      cancer at the Institute of Radiotherapy and Oncology, Hospital Kuala Lumpur. A
      retrospective analysis of 320 patients' records from 1986 to 1994 was carried
      out. Adjuvant chemotherapy was given to 98 patients. Cancers of the rectum and
      sigmoid colon constituted over 60% of the patients. All the regimes used were 5
      fluorouracil-based. The oral route was the most commonly used (55.1%). Toxicity
      was seldom the reason for stopping treatment (2%). The adjuvant treatment
      employed has been tolerable while the survival was comparable with other centres.

PMID- 10968069
TI  - Prevalence of emotional and behavioural problems in Johor Bahru District school
      children--comparing three geographical areas.
AB  - This is a cross sectional community study in Johor Bahru District. The aim of
      this study is to estimate the overall prevalence of emotional and behavioural
      deviance among the school children in three different geographical areas, and to
      identify their correlates. This paper presents the findings of phase one of a two
      stage procedure involving a total of 589 children aged 10-12 years. Using the cut
      off point validated locally, the prevalence of deviance on the parental scale was
      40% in the rural school, 30.2% in the agricultural resettlement (Felda) school
      and 32.3% in the urban school. On the teachers' assessment, the prevalence of
      deviance was 40.8% in the rural school, 10.8% in the Felda School and 8.9% in the
      urban school. There was significantly higher prevalence of deviance in the rural
      school on the teachers' scale. In the rural school, significantly higher
      prevalence of deviance was found among boys.

PMID- 10968070
TI  - The significance of aches/pains among workers in an electronics factory.
AB  - Three hundred and fifteen female workers with at least three months' employment
      history in a factory manufacturing disk drives were studied. Each worker
      completed a self-administered questionnaire on their personal particulars, hours
      of work, opinion on the work and the workplace and the presence and severity of
      aches/pains experienced over the past one month. One hundred and forty one
      (44.8%) of the workers had complaints of aches/pains. Of these, 81 (57.5%)
      reported an improvement in their symptoms during their off-days. 59 (41.8%) had
      symptoms affecting two or more sites. The most commonly affected sites were the
      hands and shoulders, followed by the head and back. There was no significant
      difference in the prevalence of symptoms between workers from the different work
      stations. Ninety four (66.7%) of these workers reported that the pains that were
      severe enough to affect their activities. 76 (53.9%) had to seek some form of
      medical treatment while 33 (23.4%) had to be on medical leave. However, the
      physical examinations of this group of workers were normal. The symptoms appeared
      to be influenced by their attitude towards work. A significantly higher number of
      workers with symptoms expressed dissatisfaction with work and had complaints of a
      noisy and cold environment. The study showed that workers' morale and the quality
      of the work environment may play an important role in improving their general
      well-being.

PMID- 10968071
TI  - Audit of new long-stay patients in Permai Mental Hospital, Johor.
AB  - We report a cross-sectional descriptive study of 90 new long-stay patients (NLS)
      (i.e. those who had been resident for six months to three years in Permai Mental
      Hospital, Johor) and studied from April to June, 1995. The age of this sample
      ranged from 18 to 85 years. Two subgroups were observed (i.e. younger NLS
      patients aged 18 to 34 years and older NLS patients aged 35 to 85 years). Among
      the younger NLS patients, the commonest diagnosis was schizophrenia (51.2%),
      followed by mental retardation with related problems (24.4%). Sixty-one percent
      of these younger patients had a history of serious violence or dangerous
      behaviour. Older NLS patients were likely to have a diagnosis of schizophrenia
      (79.6%), followed by mood disorder (6.1%) and dementia (4.1%). Forty seven
      percent of these older group had history of danger to others and 57.1% were at
      moderate or severe risk of non-deliberate self-harm. Focusing on the
      schizophrenic patients, all of them had some form of psychopathology, either
      positive, negative or general symptoms and about one-fourth were assessed to pose
      a risk for aggression.

PMID- 10968072
TI  - Non-familial haemophagocytic lymphohistiocytosis in children.
AB  - Haemophagocytic Lymphohistiocytosis (HLH) is a rare clinical illness with a high
      mortality. There are reported effective treatment and a favourable outcome if
      diagnosed early. Five cases of childhood non-familial HLH seen over a 3 year
      period in our hospital are presented. The diagnosis was not suspected in the
      referring hospitals even after a bone marrow biopsy examination in two cases.
      Delay in referral was between 2 weeks to 2 months. A viral trigger was detected
      in only two cases. There were two deaths. Cause of death in both cases were
      cytomegalovirus pneumonitis and disseminated intravascular coagulopathy. Respond
      to treatment was better if started earlier. One case spontaneously resolved.
      Earlier diagnosis will lead to prompt treatment and a better outcome.

PMID- 10968073
TI  - Paediatric day care anaesthesia--our first two years experience at the Paediatric
      Institute, Hospital Kuala Lumpur.
AB  - The first two years anaesthetic experience of paediatric day care surgery is
      reviewed. Four hundred and three patients underwent 447 general surgical
      procedures. The mean age of the patients was 5.4 years with the youngest being 5
      months old. The commonest procedures performed were herniotomy, circumcision,
      correction of hydrocoele and orchidopexy. The overall postoperative admission
      rare was 2.5%. No major complications were seen. Anaesthesia for paediatric day
      care surgery is safe provided patients are carefully selected and evaluated,
      appropriate anaesthetic management instituted and proper discharge criteria
      adhered to.

PMID- 10968074
TI  - In-vitro susceptibility of Burkholderia pseudomallei to cefoperazone-sulbactam
      combination.
AB  - Melioidosis is endemic in Malaysia. Emerging resistance with new and current
      antimicrobial agents has underscored the need to look further for new
      antimicrobial agents for the treatment of melioidosis. Hence, we evaluated the in
      vitro susceptibility of fifty locally isolated strains of Burkholderia
      pseudomallei, the causative agent of melioidosis to cefoperazone-sulbactam
      combination using the method of NCCLS. All the fifty strains tested were
      susceptible in-vitro to cefoperazone-sulbactam. The MIC90 of the organism for
      cefoperazone-sulbactam was 4 mg/L. The results of our findings suggested that
      cefoperazone-sulbactam may be useful in the treatment of melioidosis.

PMID- 10968075
TI  - Helicobacter pylori and peptic ulcer disease--a causal link.
AB  - The link between Helicobacter. pylori and peptic ulcer disease in 1997 is an
      irrefutable one. The association between infection and ulcerogenesis has been
      shown to be biologically plausible with induction of epithelial inflammation and
      cell damage and its effect on gastrin/acid homeostasis. The association of H.
      pylori infection and peptic ulcer disease is a close and consistent one. There is
      ample evidence indicating that H. pylori eradication results in virtual abolition
      of ulcer relapse. Several studies have demonstrated that eradication of H. pylori
      results in ulcer healing and there is evidence showing a temporal relationship
      between infection and development of peptic ulcer disease.

PMID- 10968076
TI  - Carbon monoxide poisoning from gas water heater installed and operated in the
      bathroom.
AB  - Two cases of carbon monoxide poisoning involving 3 victims occurred in Cameron
      Highlands in the months of August and September 1995. Two of the victims were
      found dead in the bathrooms where they were taking a bath while the other one
      survived. Blood toxicology from the post mortems revealed high levels of carbon
      monoxide. The only significant source of carbon monoxide in both cases were the
      gas water heaters which were installed in the bathrooms. A multigas detector was
      used to monitor the level of carbon monoxide in one of the bathrooms and carbon
      monoxide was found to be produced to 1200 ppm in 16 minutes during operation of
      the heater. Carbon monoxide poisoning from gas water heaters installed in
      bathroom is a significant hazard.

PMID- 10968077
TI  - A unique case of tetrodotoxin poisoning.
AB  - A 69-year-old lady who was referred by her general practitioner with a diagnosis
      of food poisoning developed cardiorespiratory arrest shortly after arriving at
      the Casualty Department. Cardiac output was successfully restored with
      resuscitation but she had to be mechanically ventilated due to the absence of any
      spontaneous respiratory effort. Assessment 24 hours after admission, showed fixed
      and dilated pupils with brain stem areflexia. Her family was told that the
      prognosis was hopeless. Surprisingly, her condition rapidly improved a day later
      and she eventually had a good recovery. Her condition was actually due to severe
      tetrodotoxin poisoning after eating roe of the puffer fish and it was fortunate
      that appropriate aggressive resuscitation was instituted to revive the patient
      from her critical state.

PMID- 10968078
TI  - Second malignant neoplasms: an increasingly recognized complication of childhood
      cancer.
AB  - Second malignant neoplasms (SMN) are an increasingly recognized late complication
      seen in childhood cancer survivors. A total of 3 cases of SMN have been found in
      the Department of Paediatrics, University Hospital Kuala Lumpur after a 15-year
      experience of treating childhood malignancies. Two cases are described here. The
      first developed abdominal non-Hodgkin's lymphoma 3 years after undergoing an
      allogeneic bone marrow transplant for second relapse of acute lymphoblastic
      leukaemia, while the second child developed myeloid leukaemia two years after
      completing treatment for acute lymphoblastic leukaemia. Progress in the
      management of childhood cancer in Malaysia and the availability of bone marrow
      transplantation facilities have increased the number of childhood cancer
      survivors; leading to increased incidence of SMN.

PMID- 10968079
TI  - Primary repair with in-situ interposition graft for infrarenal mycotic aortic
      pseudoaneurysm.
AB  - This is a case report of a pseudoaneurysm due to Salmonella aortitis in a 52 year
      old man. The condition is rare and represents one of the few cases reported in
      Malaysia. The diagnosis was made preoperatively by ultrasonography and computed
      tomography. This was confirmed at surgery where there was a 3 cm defect at the
      posterior wall of the aorta at L2/3 level. The aneurysmal sac extended to the
      retrocrural space at the 12th vertebra level cranially on the right side to the
      lower border of the 3rd lumbar vertebra caudally. It had a smooth fibrous wall
      and contained a mixture of organised haematoma and pus. At operation the aneurysm
      was excised, the affected region was carefully debrided and the aorta grafted
      with an in-situ in-lay graft. Antibiotic therapy was instituted until clinical
      response was evident, leukocytosis was reduced and blood culture was negative.
      However 4 months after surgery, the patient returned in irreversible shock and
      succumbed to disseminated intravascular coagulation secondary to massive upper
      gastrointestinal haemorrhage from an aortoduodenal fistula.

PMID- 10968080
TI  - The use of gutta-percha point to locate the origin of facial sinus.
AB  - Infection from the wisdom teeth usually causes severe swelling at the region of
      the angle and body of the mandible. Occasionally, it tracts outward to form a
      cervicofacial sinus. This paper demonstrates the use of gutta-percha point to
      locate the origin of a cervicofacial sinus due to an asymptomatic impacted wisdom
      tooth. The advantage of using gutta-percha point is discussed.

PMID- 10968081
TI  - Acute myocardial injury: an entity of acute coronary syndromes.
AB  - A 46-year-old Indian man was admitted with unstable angina (Braunwald's class
      IIIB1)--the chest pain at rest was associated with inferolateral ischaemia on the
      ECG at admission. His serial total creatine kinase levels were elevated but CKMB
      was not detected. Serial serum troponin T levels were significantly raised
      suggesting the presence of significant acute myocardial injury.

PMID- 10968082
TI  - Clubbing of the fingers in patients with primary lung cancer.

PMID- 10968083
TI  - Viral hepatitis.

PMID- 10968084
TI  - Malaysia's ageing issues.

PMID- 10968085
TI  - Geriatric practice in Malaysia: issues and challenges.

PMID- 10968086
TI  - The elderly in Malaysia: demographic trends.

PMID- 10968087
TI  - Ophthalmic problems among the elderly in Malaysia.

PMID- 10968088
TI  - Surgical problems among the elderly in Malaysia.

PMID- 10968089
TI  - Psychiatric problems among the elderly in Malaysia.

PMID- 10968090
TI  - Orthopaedic problems in the elderly.

PMID- 10968091
TI  - Social problems and care of the elderly.

PMID- 10968092
TI  - A comparative study of first and third year student nurses' knowledge and
      attitudes on the elderly and ageing.
AB  - A comparative study was carried out to assess Year I and Year III student nurses'
      attitudes and knowledge of the elderly. Significantly more Year I students
      disagreed that the elderly had a capacity to learn (chi 2 = 11.08, p = 0.0006).
      Year III students were significantly more likely to obtain information about the
      elderly from the mass media, agencies, and relatives but not from health
      personnel. Nearly all respondents (96.25%) in the study wanted to know more about
      the elderly. Only 3 of the 14 questions on ageing revealed significant
      differences in knowledge between the two groups. The basic course in gerontology
      should be expanded and revised to dispel erroneous attitudes, allow better
      understanding of the ageing process, and ensure entry-level competence in caring
      for older people.

PMID- 10968093
TI  - Active resuscitation in Malaysian district hospitals--is it adequate?
AB  - Adequacy of active resuscitation in collapsed inpatients aged 12 and above
      (excluding those with terminal illness) were studied in 6 Malaysian district
      hospitals for 3 months starting 1/1/93. Results showed 59.5% (25 out of 42
      inpatients) were inadequately resuscitated measured by: failure of nurses to
      initiate resuscitation (24%), duration of resuscitation less than 30 minutes
      (42%) and incompletely equipped emergency trolleys (44%). Questionnaires revealed
      lack of knowledge and training in cardiopulmonary resuscitation in medical staff.
      Regular cardiopulmonary resuscitation courses, regular spot checks on emergency
      trolleys and management protocols on active resuscitation are recommended. Each
      hospital should design its own criteria for adequacy.

PMID- 10968094
TI  - Acute renal failure requiring dialysis--a 5 year series.
AB  - A retrospective review of 246 patients with established acute renal failure (ARF)
      needing dialysis from 1990-1994 is reported from Hospital Sultanah Aminah, Johor
      Bahru. Peritoneal dialysis was more commonly used than haemodialysis or
      haemofiltration. Patients on mechanical ventilation in Intensive Care Unit (ICU)
      who were hypercatabolic and fluid overloaded were treated with haemofiltration.
      Males outnumbered females by a ratio of 1.5:1. The majority were Malays (61.4%).
      Most patients were from the district of Johor Bahru, but 41.5% were from other
      districts in the Johor state. The mean age was 47.1 years (SD 18.2). The ARF was
      caused by acute tubular necrosis in 55.3%, post-renal obstruction in 22.8%,
      nephrotoxins in 5.7% and other causes in 16.2%. The proportions of patients
      referred from the medical, surgical and obstetric and gynaecology units were
      50.8%, 45.5% and 3.7% respectively. The mortality rate was 48%. Patients with
      established ARF should be dialysed early as they tolerate uraemia poorly.
      Prevention is by prompt treatment of patients with sepsis, avoidance of
      hypovolaemia and nephrotoxic drugs.

PMID- 10968095
TI  - Job satisfaction of doctors in Negeri Sembilan.
AB  - A cross sectional study was carried out in Negeri Sembilan to identify factors
      associated with job satisfaction of doctors serving in Ministry of Health and
      their intentions to resign. All Ministry of Health doctors currently working in
      Negeri Sembilan were included in the study and data collection was done via a
      self-administered postal questionnaire. The response rate was 69.4%. Out of those
      who responded, only 31.3% had global job satisfaction, with the majority
      dissatisfied. Intention to resign was high among 32.7% of the respondents.
      Factors found to be significantly associated with job satisfaction were age, job
      designation, income, duration of service and intention to resign. Intention to
      resign was found to be significantly associated with ethnicity and income. From
      logistic regression, predictors of job satisfaction identified were age, place of
      first graduation, and satisfaction with status and autonomy, satisfaction with
      career development, satisfaction with workload and satisfaction with transfers.
      Predictors of intention to resign were race, income and global job satisfaction.

PMID- 10968096
TI  - A comparison of antiemetic efficacy of droperidol alone and in combination with
      metoclopramide in day surgery anaesthesia.
AB  - We have studied the antiemetic efficacy of droperidol alone, and in combination
      with metoclopramide in first trimester termination of pregnancy in day surgery.
      The aim was to determine whether the addition of metoclopramide could further
      reduce the incidence of postoperative nausea and vomiting (PONV) but avoid
      excessive sedation. Group I (control, n = 40) received i.v. droperidol 0.625 mg
      at induction. Group II (study, n = 40) received i.v. droperidol 0.625 mg and i.v.
      metoclopramide 10 mg at induction. The incidence of nausea at 1 and 2 hours
      postoperatively was 23% and 10% in group I, and 5% and nil in group II
      respectively. The difference in the incidence of nausea was significant at p <
      0.05 at one hour but not at two hours postoperatively. No patients vomited. There
      was no difference in the sedation and pain score between them. We did not observe
      any significant side effects attributable to either drug. All patients were
      discharged home within 3 hours. We conclude that in the prevention of PONV, the
      combination of metoclopramide and droperidol is superior to the use of droperidol
      alone at one hour but not at two hours postoperatively.

PMID- 10968097
TI  - Day surgery: a post operative audit.
AB  - Fifty-five patients were followed up after day surgery for breast lumpectomy. It
      was found that local infiltration with bupivacaine significantly decreased
      analgesic requirement in recovery. Almost half of the patients could not be
      contacted during the 24 hour post-operative follow-up by telephone. 7.1%
      complained of severe pain despite oral analgesics. 14.3% of patients had queries
      regarding wound care and 78.6% of the patients were willing to undergo day
      surgery again. Ongoing patient education and good post operative analgesia are
      crucial to enable successful establishment of ambulatory surgery. Post-operative
      follow-up is encouraged to audit clinical and social outcomes of day surgery.

PMID- 10968098
TI  - A comparative study on family, social supports and mental health of rural and
      urban Malay women.
AB  - The present study aims to compare the family's social environment, social
      supports and mental health of Malay women from rural and urban areas. Equal
      number (n-184) of Malay women from similar socio-economic back grounds were
      chosen from the rural areas of Kedah and urban areas of Pulau Pinang using the
      stratified random sampling method. The results indicated significantly higher
      level of mental health problems among the rural respondents when compared with
      the urban subjects. Among the family related variables included in the present
      study, cohesiveness, moral religious emphasis and organization and intellectual
      and cultural orientation were found to be significantly associated with the
      mental health problems of rural respondents. Whereas, only one variable, namely,
      active recreational orientation was found to be having an impact on the mental
      health of urban respondents. Similarly, deficiencies in the social support
      perceived from family and other members of the community were found to be
      significantly associated with the mental health problems of rural samples when
      compared to the social support perceived from the others for the urban subjects.
      The implications of these observations are discussed.

PMID- 10968099
TI  - Post meningitic sensori-neural hearing loss in children--alterations in hearing
      level.
AB  - Post meningitic sensori-neural hearing loss was studied in forty new cases of
      bacterial meningitis and ten cases of viral meningitis treated at the Pediatric
      Institute, Kuala Lumpur Hospital from April 1991 to March 1992. Hearing
      assessment at 2 weeks, 3 months and 6 months following the diagnosis of
      meningitis using Brain Stem Evoked Response Audiometry showed that hearing loss
      was prevalent only in patients with bacterial meningitis. Hearing loss was
      detected in 32.5% of these patients during the acute phase of the disease, 22.8%
      after 3 months and 24.2% after 6 months. In 63.6% of the affected cases, hearing
      loss was bilateral. In 61.5% of the patients who had hearing loss during the
      acute phase of the disease, it was permanent, 16.7% had either partial or
      complete recovery and, 15.4% had deterioration in hearing level. In 2 cases the
      subsequent hearing level was unknown. The risk of developing sensori neural
      hearing loss was found to be significantly higher in patients who developed other
      neurological sequelae. The study highlights the importance of performing repeated
      hearing assessment in children with bacterial meningitis and the difficulty in
      appropriate selection of hearing aids in the early stages.

PMID- 10968100
TI  - Conjoined twins in a triplet pregnancy.
AB  - Conjoined twins in a triplet pregnancy is an extremely rare occurrence. We
      present here, a 27-year-old multigravida with gestational diabetes and a
      conjoined twins in a triplet pregnancy.

PMID- 10968101
TI  - Peritoneal trophoblastic implant.
AB  - A case of persistent trophoblastic tissue on the pelvic peritoneum is presented.
      While most cases are secondary to conservative surgery for tubal ectopic
      pregnancy, primary implantation can also occur as highlighted by this case. A
      brief pathophysiology of the condition is presented. The importance of monitoring
      the serum for beta subunit human chorionic gonadotrophin (HCG) is emphasised.

PMID- 10968102
TI  - Pregnancies after microinjection of human spermatozoa into human oocytes.

PMID- 10968103
TI  - Differences in public and private health services in a rural district of
      Malaysia.

PMID- 10968104
TI  - Typhoid fever: present and future.
AB  - Typhoid fever (TF), a systemic prolonged febrile illness, continues to be a
      worldwide health problem especially in developing countries where there is poor
      sanitation and poor standards of personal hygiene. The worldwide incidence of TF
      is estimated to be approximately 16 million cases annually with 7 million cases
      occurring annually in SE Asia alone. More than 600,000 people die of the disease
      annually. The pathogenesis of TF is beginning to be understood. The clinical
      features and diagnosis of TF are well known. New diagnostic methods have yet to
      gain universal acceptance. Traditional treatment with the first-line antibiotics
      (i.e. chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole) though
      still being used in most developing countries are gradually being replaced with
      shorter courses of treatment with third generation cephalosporins or
      fluoroquinolones especially with the growing incidence of multi-drug resistant S
      typhi strains (MDR-ST). MDR-ST strains are particularly common in the Indian
      subcontinent; Pakistan and China. The presently available vaccines are far from
      satisfactory in terms of safety, efficacy and costs. Newer vaccines have been
      developed and are presently undergoing clinical trials in human volunteers.

PMID- 10968105
TI  - HIV in south and South-East Asia.

PMID- 10968106
TI  - Epidemiology and clinical characteristics of HIV-infected patients in Kuala
      Lumpur.
AB  - Between 1987 to 1995, a total of 334 patients infected with HIV were treated at
      the Hospital Kuala Lumpur. There were 159 Malays, 108 Chinese, 64 Indians, and 3
      from other ethnic groups. Three hundred and twenty-one (96.1%) of these
      individuals were males and 262 (65.9%) were between the ages of 26-45 years.
      Intravenous drug users made up 77% (256) of the attributable risk behaviour from
      the group although many of them also had added risk behaviours like heterosexual
      activity with multiple partners (50 patients), tattoos (7 patients), homosexual
      practice (4 patients) and previous transfusions (3 patients). The others acquired
      their infection through heterosexual promiscuity (59 patients), homo/bisexual
      activity (7 patients), previous transfusion (5 patients) and tattoos (1 patient).
      Sixty-six patients (all males) had since progressed to full blown AIDS and 10
      have died. The two commonest AIDS-defining events were tuberculosis infection and
      Pneumocystic carinii pneumonia occurring in 37 (56%) and 15 (22.7%) of patients
      respectively. Forty-one patients with AIDS presented for the first time with
      their AIDS-defining infections. The mean CD4 count of the patients when they
      progressed to AIDS was 130/mm3. The mean time for progression from "known"
      seropositivity to AIDS was 2.42 years. These results suggest that Malaysians
      infected with HIV are not coming forward for treatment until they are in the
      advanced stage of the disease.

PMID- 10968107
TI  - Sexual behaviour and HIV knowledge among Dermatology cum Genitourinary Clinic
      attendees, Johor Bahru, Malaysia.
AB  - A study was conducted in the Dermatology cum Genitourinary Clinic, Hospital
      Sultanah Aminah Johor Bahru to determine a local population's knowledge of HIV
      and their sexual behaviour in relation to it. A total of 231 men and 217 women
      were interviewed. The sexual culture seen is one of relatively late age of first
      sexual intercourse, low level of partner change and low level of condom use. Men
      reported a higher involvement in risk behaviour. Nearly all the respondents
      (95.8%) have heard of HIV/AIDS but had incorrect perceptions of its mode of
      transmission and its associations with risk groups. This study enable us to gain
      background information about our patients sexual behaviour and HIV knowledge.
      There is a need to continue HIV education to improve our public's HIV knowledge
      and the results of this study provides a baseline against which future
      educational interventions can be gauged.

PMID- 10968108
TI  - Post-caesarean septicaemia in Kandang Kerbau Hospital, Singapore, 1993-1995.
AB  - We reviewed all documented cases of septicaemia following caesarean deliveries in
      Kandang Kerbau Hospital between 1st January 1993 to 31st December 1995. There
      were 22 cases of septicaemia among 8201 caesarean births, and hence the incidence
      is 2.7:1000. There were 45,412 deliveries, and the overall caesarean section rate
      was 18.1%. Among the 22 documented cases of septicaemia which came under this
      study, the most common clinical conditions found were endomyometritis (7 cases),
      urinary tract infection (6 cases), and wound infection (3 cases). One of the
      three cases with wound infection also had pneumonia. There was one patient who
      had mild transient myocarditis. We could not determine with certainty any site of
      infection in five patients. The most common bloodstream bacterial isolates was
      Staphylococcus aureus (16), while the uncommon ones were Acinetobacter baumanii
      (2), Escherichia coli (1), Klebsiella sp. (1), Staphylococcus epidermidis (1),
      Streptococcus Group F (1), Peptostreptococcus species and Veillonella species
      (1). There was no mortality and prompt, vigorous treatment had led to uneventful
      recovery in all the cases.

PMID- 10968109
TI  - The prevalence of hepatitis B surface antigen and anti-HCV antibody in paediatric
      oncology patients in Hospital Universiti Sains Malaysia.
AB  - This study examined the prevalence of hepatitis B and C markers in 55 paediatric
      oncology patients who had completed treatment at the Hospital Universiti Sains
      Malaysia in Kota Baru. All these children had received blood products and had
      been treated between 1985-1996. Forty seven per cent of patients were positive
      for hepatitis B or C. Twenty nine per cent were positive for hepatitis C and
      twenty two per cent were HBsAg positive. Two children were positive for both and
      none were HIV positive. Four children had an elevated ALT level and one child had
      jaundice and hepatomegaly. Some children were marker-positive despite
      immunization and screening of blood.

PMID- 10968110
TI  - The incidence of human herpesvirus 6 infection in children with febrile
      convulsion admitted to the University Hospital, Kuala Lumpur.
AB  - From October 1996 to March 1997, 31 children with febrile convulsions were
      admitted to the University Hospital, Kuala Lumpur. Human Herpesvirus 6 (HHV 6)
      was virologically and/or serologically confirmed to be the cause of the febrile
      episode in 5 of these children (16.1%). Age, sex and other associated clinical
      features (diarrhoea, cough, running nose and type of seizure) were not useful in
      differentiating cases of febrile convulsion due to HHV 6 from those of other
      aetiology. However, uvulo-palatoglossal junctional ulcers were noted in children
      in whom the cause of the seizure could be attributed to HHV 6 but not in the
      remaining cases in the study group. HHV 6 DNA was detected in peripheral blood
      mononuclear cells from all patients with febrile convulsions attributed to HHV6,
      and in patients shown serologically to have already been exposed to the virus by
      nested polymerase chain reaction amplification. Only genotype HHV 6B was detected
      from patients with seizure due to HHV 6 but both genotype 6A and 6B were detected
      in the remaining cases studied.

PMID- 10968111
TI  - Characteristics of Malaysian infants with biliary atresia and neonatal hepatitis.
AB  - Cholestatic disorders of infancy (viz neonatal hepatitis and biliary atresia)
      have not been well studied in Malaysia. In a retrospective study in the
      Department of Paediatrics, University Hospital, Kuala Lumpur from January 1982
      through December 1991, a total of ninety-three infants with such conditions were
      identified: 35 (38%) had biliary atresia, 58 (62%) neonatal hepatitis. There was
      a statistically significant male preponderance in the neonatal hepatitis group (P
      = 0.020). There was no significant difference in the racial distribution and in
      the proportions of low birthweight infants between the two groups of disorders.
      When the biliary atresia group was compared with the neonatal hepatitis group,
      significant differences were observed in the age of presentation (mean +/- SD)
      9.8 +/- 6.8 VS 20 +/- 17.3 weeks (P < 0.001), proportion of infants with
      prolonged jaundice (> seven weeks) 28/35 (80%) VS 20/58 (34.5%) (P < 0.00001),
      occurrence of alcoholic stools 26/35 (74.3%) VS 27/58 (46.6%) (P = 0.020), liver
      size (mean +/- SD): 4.3 (1.6 cm VS 3.3 +/- 1.8 cm (P < 0.01) and splenic size:
      2.5 (1.8 cm VS 1.4 (1.2 cm (P < 0.001). There was however considerable overlap
      between the two groups in these features at presentation, making clinical
      differentiation between the two conditions difficult. Infants with cholestasis
      tended to present late, compromising the chance of survival. In order to improve
      the medical care of these patients, these conditions must be emphasised during
      the training of medical practitioners, and efforts to increase public awareness
      of these conditions must be created.

PMID- 10968112
TI  - Health status of senior civil servants in Kuala Lumpur.
AB  - 733 senior civil servants comprising 520 males and 213 females with a mean age of
      44 years (range 25-56 years) were screened for their health status. The sample
      population comprised of 67.9% Malays, 22.5% Chinese, 9.1% Indians and 0.4% other
      ethnic origins. The subjects' medical histories were recorded and a full medical
      examination including anthropometric measurements (weight, height, waist and hip
      circumference), blood biochemistry and urine analysis, chest X-ray and
      electrocardiograms were done. The results obtained showed that 36.0% of the study
      population were overweight with 6.5% being obese. Of this 32.0% had central
      obesity. 15.2% of the subjects had systolic hypertension (systolic BP > or = 140
      mmHg) whilst 27.6% had diastolic hypertension (diastolic BP > or = 90 mmHg).
      Hyperlipidaemia was common, with 75.2% subjects having raised cholesterol, 19.9%
      raised triglycerides, 50.2% raised LDL-C, 74.6% raised TC:HDL-C and 26.6% raised
      LDL:HDL-C. An elevated blood glucose was found in 8.4% subjects, whilst urine
      sugar was detected in only 2.6%, and a raised uric acid was found in 2.8%
      subjects. The prevalence of hypertension, raised blood glucose and
      hyperlipidaemia increased with age with more males affected than females.
      Although hypercholesterolaemia appeared more frequently amongst the Malays, the
      Indians, by comparison had the highest prevalence for a raised LDL:HDL-C ratio, a
      reflection of the increase in LDL-C and a concomitant decrease in HDL-C. The
      latter findings indicate that the Indians are at greater risk for the development
      of coronary heart disease than the Chinese and Malays. In addition, the mean
      levels of serum cholesterol found in this study seemed to have exceeded the
      levels found in populations in the industrialised countries such as the USA.
      There is thus an urgent need for more public health campaigns aimed at the
      reduction and control of such coronary risk factors.

PMID- 10968113
TI  - Prevalence of coronary risk factors in a sample of Chinese women in Kuala Lumpur.
AB  - Several risk factors for cardiovascular disease amongst a sample of urban Chinese
      women were investigated. These factors included body mass index (BMI), waist hip
      ratio, total blood cholesterol (TC), HDL-cholesterol and Lp(a) levels, blood
      pressure, cigarette smoking, family history of chronic disease, dietary habits
      and frequency of selected food intake. The subjects were found to have coronary
      risks with respect to BMI and TC level, both of which increased with age of the
      women. Hypertension, HDL-cholesterol and Lp(a) levels appeared not to pose as
      risk factors amongst these subjects. Dietary habits and intake showed significant
      correlations with subjects' BMI status. Health promotion is called for towards
      reducing the modifiable coronary risk factors.

PMID- 10968114
TI  - A comparison between the pregnancy outcome of women with gestation diabetes
      treated with glibenclamide and those treated with insulin.
AB  - The pregnancy outcome of 33 women with gestational diabetes who were treated with
      glibenclamide and changed to insulin if glibenclamide failed, were compared with
      the pregnancy outcome of 21 women with gestational diabetes treated
      conventionally with insulin. The pregnancy outcome, with regard to the overall
      glycaemic control, rates of preterm labour, neonatal hypoglycaemia, fetal
      macrosomia, perinatal morbidity and mortality, were not statistically different
      between the two treatment groups. The limited number of women studied, and the
      non-random allocation of these women to each treatment group however, could have
      influenced these results. There were a few observed differences in the pregnancy
      outcome between the two treatment groups, which although were not statistically
      significant, caused some concern. In particular we noted an increased rate of
      fetal macrosomia in the glibenclamide treated group, which in theory could have
      been drug mediated.

PMID- 10968115
TI  - Audit of diabetes in Perak outpatient departments.
AB  - Adequacy of diabetic management in 5 Perak outpatient departments was studied in
      April 1996. Two hundred diabetic patients' records were analysed. All doctors and
      100 patients answered questionnaires on diabetes. Fifty five percent of doctors
      had adequate knowledge. Patients' knowledge varied between centres (13% to 80%
      adequacy). Most records had insufficient data to determine adequacy of early
      detection. Centres with screeners had adequate weight and blood pressure
      measurement. Overall control and monitoring of diabetes were inadequate. Referral
      of complications were delayed in 2 centres. Refresher courses for doctors,
      patient health education, protocols, screeners and physician visits are
      recommended.

PMID- 10968116
TI  - Evaluation of the sensitivity in vitro of Plasmodium falciparum and in vivo of
      Plasmodium chabaudi Malaria to various drugs and their combinations.
AB  - K1 strain of Plasmdoium falciparum is resistant in vitro to chloroquine,
      pyrimethamine and sulfadoxine. Response of this strain to combinations of
      antimalarial drugs in the in vitro hypoxanthine incorporation test was coupled
      with that of a line of strain NF54 relatively sensitive to chloroquine and fully
      sensitive to other antimalarials. Pyrimethamine and sulfadoxine showed
      potentiative synergism against NF54 and less marked against K1. Erythromycin and
      chloroquine showed potentiation, but less marked against NF54. Quinine and
      clindamycin had an additive effect against NF54 but potentiated against K1.
      Combinations of chloroquine with quinine or amodiaquine or of amodiaquine with
      clindamycin or erythromycin showed mild antagonistic or additive effects. In vivo
      studies in mice, using the 4-day suppressive test, the AS(3CQ) clone of
      Plasmodium chabaudi was resistant to pyrimethamine and chloroquine but sensitive
      to sulfadoxine. Similar combinations as above were carried out and their
      responses were compared between the resistant and sensitive strains. For both
      strains, the combinations of chloroquine-erythromycin, pyrimethamine-sulfadoxine,
      quinine-clindamycin showed potentiation; antagonistic effects were observed in
      chloroquine-amodiaquine combinations whereas when amodiaquine combined with
      erythromycin the effect was additive. Amodiaquine-clindamycin and chloroquine
      quinine combinations have an antagonistic effect against the sensitive strain but
      additive against the resistant strain.

PMID- 10968117
TI  - Teaching of basic life support in the undergraduate medical curriculum.
AB  - There is now increased public awareness of the value and role of cardiopulmonary
      resuscitation (CPR). It is therefore not surprising that the public expects a
      reasonable level of expertise of medical doctors in the application of the CPR
      techniques during emergency situations. Newly qualified doctors often lack
      confidence and are usually at a loss when faced with such situations as they have
      never had practical training before graduation. Most doctors are gradually
      introduced to CPR as part and parcel of their clinical experience. Many begin to
      attend formal CPR workshops later in their careers. Medical schools are expected
      to produce well trained doctors who are competent in clinical practice which
      include the techniques of basic resuscitation. By virtue of their expertise in
      airway management and clinical resuscitation, anaesthesiologists can
      significantly contribute to the teaching of CPR in the undergraduate medical
      curriculum. This is a retrospective review of Basic Life Support programmes
      conducted at the Department of Anaesthesiology, Faculty of Medicine, Universiti
      Kebangsaan Malaysia.

PMID- 10968118
TI  - [The risk of road traffic accidents among primary school children in Kuala
      Terengganu].
AB  - A case control study was conducted in 1996 among primary school student in
      Terengganu. The objective of the study is to determine the relationship between
      road traffic accidents and factors such as socio-economic status, distance from
      school, number of siblings, behavioural problems, knowledge and attitudes of
      pupil and their parents towards road safety and parents' educational status. A
      total of 140 cases was obtained from 3 urban schools and 3 from rural schools.
      Cases were matched with control according to age sex and locality of residence.
      There were significant associations between road traffic accidents and pupils'
      knowledge regarding road crossing (OR = 0.40, 95% CI = 0.19-0.85), parental
      supervision (OR = 0.43, 95% CI = 0.19, 0.64) and parents having driving licences
      (OR = 0.99, 95% CI = 0.856-0.999). Road safety education for pupils and parental
      supervision are key measures in preventing road traffic accidents among primary
      school children.

PMID- 10968119
TI  - Prevalence and antibiotic susceptibility of Ureaplasma urealyticum in Malaysian
      neonates with respiratory distress.
AB  - Ureaplasma urealyticum was isolated from the endotracheal aspirates of 39 (21.4%)
      of 182 neonates with respiratory distress requiring ventilatory support.
      Mycoplasma hominis was isolated from one (0.5%) neonate. Bacterial cultures were
      negative in 123 (67.6%) neonates. Antibiotic susceptibility test carried out on
      ten isolates of U. urealyticum showed that all the organisms were sensitive to
      erythromycin but resistant to lincomycin and sulfamethoxazole trimethoprim. All,
      except one, U. urealyticum were sensitive to tetracycline and minocycline. Two
      isolates were resistant to ciprofloxacin. This study showed that U.urealyticum
      was a common organism isolated from the endotracheal aspirates of neonates with
      respiratory distress.

PMID- 10968120
TI  - Parasitic infections among aborigine children at Post Brooke, Kelantan, Malaysia.
AB  - This study investigated the prevalence of parasitic infections among aborigine
      children at Post Brooke, Kelantan. Eighty-four formalin-fixed specimens and 78
      PVA-fixed specimens were obtained. 79.8% and 35.9% of the samples were positive
      for helminth ova and protozoa respectively. The parasites detected (single plus
      mixed infections) were A. lumbricoides (50/84, 59.5%), T. trichiura (35/84,
      41.7%), hookworm (5/84, 6.0%), S stercoralis (1/84, 1.2%), G. intestinalis
      (18/78, 23.1%), E. histolytica (7/78, 9.0%) and E. coli (7/78, 9.0%). Two hundred
      thick blood film examinations detected only one case of Plasmodium falciparum
      infection. A high prevalence of intestinal parasitic infections among the
      children at Post Brooke was demonstrated in this study; thus there is an urgent
      need to improve the hygiene, education and living standards of this population.

PMID- 10968121
TI  - Guidelines for the management of childhood asthma--a consensus statement.

PMID- 10968122
TI  - Interstitial lung disease in children--a report of four cases.
AB  - Interstitial lung disease (ILD) is very rare in children. In the majority of
      cases the aetiology is unknown. Very little is known about the clinical course of
      this condition in children. Prognosis may be influenced by sex, age of onset of
      symptoms, radiographic features, presence of right ventricular hypertrophy and
      histopathology. We report our experience in managing four children with
      interstitial lung disease. All these children presented in early infancy with
      cough, respiratory distress, cyanosis and failure to thrive. Three of these
      children had finger clubbing and right ventricular hypertrophy. All patients
      received oral steroids. Chloroquine was added in two patients who showed no
      response. A trial of oral cyclophosphamide was started in one patient who failed
      with both drugs. One child is oxygen independent while another is on home oxygen
      therapy. The other two patients eventually died.

PMID- 10968123
TI  - A preliminary report on anaesthesia for thoracoscopic oesophagectomy.
AB  - The anaesthetic experience in three patients undergoing thoracoscopic
      oesophagectomy is discussed. The indications for surgery and the premorbid states
      are outlined. The necessity for one-lung ventilation, with its attendant
      cardiopulmonary effects, the difficulty of patient access and the assessment of
      blood loss were the main problems encountered. Pulmonary morbidity was high in
      the post-operative period despite the avoidance of thoracotomy. Two patients
      developed persistent vocal cord paralysis. In conclusion, the role of
      thoracoscopic oesophagectomy needs further evaluation.

PMID- 10968124
TI  - A report of two non-AIDS associated Kaposi's sarcoma in Malaysia.
AB  - Kaposi's sarcoma is an uncommon cutaneous neoplasm seen classically in elderly
      males of East European or Jewish extract. It has been known to be endemic in sub
      Saharan Africa for many years. Numerous cases had been described in patients on
      long-term immunosuppressive therapy and in patients living with acquired
      immunodeficiency syndrome (AIDS). In spite of the increasing number of organ
      transplant recipients and people living with AIDS. Kaposi's sarcoma remains rare
      in Asia. We report two cases seen in Johor, Malaysia.

PMID- 10968125
TI  - Penetrating cardiac injury without tamponade.
AB  - A case of unsuspected penetrating cardiac injury is presented. It was recognised
      by the presence of bleeding into peritoneal cavity even after the source of
      bleeding from intra-abdominal organs had been stopped. It highlights the
      importance of high index of suspicion of associated cardiac injury in high
      epigastric penetrating injury.

PMID- 10968126
TI  - Nifedipine-induced hypotensive shock.

PMID- 10968127
TI  - Safety considerations in magnetic resonance imaging (MRI).
AB  - MRI is now an important diagnostic tool in medical management. There are numerous
      safety issues to be considered by the clinicians prior to requesting an MRI
      examination for their patients. These include those related to the magnetic
      field, gradient magnetic fields, the patient and contrast medium. This paper
      discusses the dangers and necessary precautions essential to reduce the risk of
      untoward complications from MRI.

PMID- 10968128
TI  - Imported infections.

PMID- 10968129
TI  - Rabies raises its ugly head once more.

PMID- 10968130
TI  - Imported malaria: a retrospective study in University Hospital, Kuala Lumpur, a
      ten-year experience.
AB  - Over a period of ten years (1983-1992), 134 malaria cases admitted to University
      Hospital, Kuala Lumpur (UHKL) were analysed. Malays constituted 27.6%, Chinese
      29.8%, Indians 9.7%, Indonesians 16.4% and other foreigners 16.4%. Therefore, of
      the total number of cases, foreigners constituted 32.8% (44) of all the malaria
      cases admitted to UHKL. Fifteen of these foreigners had chloroquine-resistant
      strains of malarial parasites. Three species of malaria were reported of which
      Plasmodium falciparum constituted the most (46.3%) (80% of these developed
      resistance to chloroquine). Plasmodium vivax was confirmed in 44.8% (10% of these
      developed resistance to chloroquine) and there was only one case of Plasmodium
      malarie infection.

PMID- 10968131
TI  - Bacterial infection of central venous catheters in short-term total parenteral
      nutrition.
AB  - Fourteen severely ill ventilated patients in an intensive care unit, requiring
      short-term total parenteral nutrition, were examined for catheter-related
      infection. Microbiological analysis using Maki's SQ technique was carried out on
      catheter exit site, catheter hub, proximal subcutaneous segment of catheter and
      catheter up. Qualitative cultures were carried out on total parenteral nutrition
      and peripheral blood samples. Twenty six of 29 catheters removed (90%) were
      culture positive but only 7 catheters were related to positive blood cultures,
      giving a catheter-related bacteremia (CRB) rate of 24%. Haematogenous seeding was
      strongly implicated in 7/29 (24%) of catheters. Patients' skin flora appeared to
      be the main source of catheter-related infection. The organisms isolated for
      patients with CRB included coagulase-negative staphylococci, Acinetobacter and
      Klebsiella. It is suggested that to control infective complications of central
      venous catheters, emphasis should be focused on specialised intravenous therapy
      teams and the use of strict protocols for insertion and care of central lines.

PMID- 10968132
TI  - The prevalence of Chlamydia trachomatis in patients with pelvic inflammatory
      disease.
AB  - Chlamydia trachomatis is recognized as the most prevalent sexually transmitted
      organism in many parts of the world. Most complications associated with
      chlamydial infection in women and their infants can be avoided by appropriate
      treatment. However, treatment is often not initiated because infections are
      frequently asymptomatic. The identification of at risk patients and treatment of
      these patients is a practical clinical approach in the reduction of transmission
      and prevention of complications. The prevalence of chlamydial infection among
      patients with pelvic inflammatory disease admitted to Seremban General Hospital
      was 22.7%. The difference in seropositivity between PID patients (20.5%) and
      antenatal controls (2.3%) was statistically significant. The corresponding
      cervical antigen detection rates were 6.8% and 2.3% respectively. Chlamydial
      infection should be screened for in gynaecological patients and antibiotic
      policies should take cognizance of the aetiological role played by this organism
      in pelvic inflammatory disease.

PMID- 10968133
TI  - A hospital based study of cancer admissions.
AB  - A study was done on patients admitted to Penang Hospital with malignant disease
      in 1995. A total of 1333 patients (638 male, 695 female) with 1335 malignancies
      were studied. The majority (77.3%) were aged 41-80 years. The commonest cancers
      in males were cancers of lung, nasopharynx, colon and rectum, leukemia and larynx
      whereas the commonest malignancies in females were of the breast, cervix, colon
      and rectum, leukemia and ovarian/lung carcinoma. The average number of admissions
      was 2.2 and the average length of stay was 12.7 days. Cancer admissions account
      for a significant proportion of the inpatient workload of Penang Hospital.

PMID- 10968134
TI  - Radiotherapy in locally advanced cancer of the cervix.
AB  - Radical radiotherapy is considered as the treatment of choice in locally advanced
      cancer cervix. In late stages radiotherapy produce optimum palliation and to some
      extent cure. Three hundred cases of cancer cervix (stage I-IV) comprising stage-I
      (7), stage-II (144), stage-III (145) and stage IV (4) were evaluated and treated
      with radiotherapy between April 1990 to July 1994. FIGO stage IB, IIA and IIB
      (early), were treated with predominant intracavitary radiotherapy (34 Gy X 2
      fractions; within one week) followed by external pelvic radiotherapy to a dose of
      36 Gy in 18 fractions; treating 200 cGy per fraction, 5 days a week. The late
      stage (stage-IIB, IIIA and IIIB, IVA) of disease were managed with initial
      external radiotherapy to a dose of 50 Gy, followed by a single intracavitary dose
      of 30 Gy to point-A. The median follow up was 33 months (range 12-72 months). The
      tumor volume less than 100 cc were associated with better survival than volume
      more than 100 cc (p < 0.05). The five year actuarial survival was 83%, 68% and
      58% respectively in FIGO stage I-III disease. There were 0.33% and 2.6% late
      grade-III bladder and rectal complications. Our experience shows effectiveness of
      radiotherapy in the management of locally advanced cancer of the cervix.

PMID- 10968135
TI  - Pilot study of formestane in postmenopausal women with breast cancer.
AB  - A pilot study of Formestane or 4-Hydroxyandrostenedione (Lentaron), a new
      endocrine agent, was conducted on 18 postmenopausal patients with locally
      advanced and metastatic breast cancer. 16 patients were evaluable for response
      and objective responses were seen in 4 patients (25%). Stabilisation of disease
      was seen in 5 patients (32%). Out of 17 patients evaluable for toxicity, 3 (18%)
      reported adverse effects including hot flushes, lethargy and myalgia. Adverse
      effects were mild, transient and no patient required discontinuation of drug. Our
      study confirms that Formestane is a well tolerated endocrine agent with low
      toxicity and reasonable efficacy in postmenopausal patients with locally advanced
      and metastatic breast cancer.

PMID- 10968136
TI  - An analysis of glaucoma patients seen at the General Hospital Kuala Lumpur over a
      five year period: 1986 to 1990.
AB  - The records of all the glaucoma patients seen at the General Hospital Kuala
      Lumpur over a five year period were analysed. The racial, age and sex
      distribution of patients with primary open angle glaucoma and primary angle
      closure glaucoma was determined. The causes of secondary glaucoma were analysed.
      As no previous records of glaucoma statistics are available in Malaysia, it is
      hoped that these findings will form an initial mosaic to build on in the future.

PMID- 10968137
TI  - Blindness and visual impairment amongst rural Malays in Kuala Selangor, Selangor.
AB  - A population-based cross-sectional study was carried out to determine the
      prevalence of visual impairment and blindness and its causes amongst the adult
      rural Malay population in the district of Kuala Selangor, Selangor. By simple
      random sampling 330 samples were selected for the study. All samples underwent
      complete ophthalmological examination. The crude prevalence of visual impairment
      and blindness were 0.7% and 5.6% respectively. Age was the most important factor
      associated with the prevalence; gender, level of education and level of income
      was not significantly related. Cataract was the commonest cause of visual
      impairment and blindness while diabetic retinopathy was the second important
      cause.

PMID- 10968138
TI  - Ureteral injuries in an obstetric and gynaecology teaching hospital.
AB  - Between November 1994 to May 1996, there was a total of eight ureteric injuries
      out of 2495 major gynaecologic operations and one ureteric injury out of 4146
      caesarean sections at the Kandang Kerbau Hospital, giving the incidence to be
      0.3% and 0.02% respectively. Antecedent operations were four abdominal
      hysterectomies, two Werthiem's hysterectomies, one laparoscopic-assisted vaginal
      hysterectomy and one caesarean section. All operations were performed by
      qualified specialists. Three patients had previous abdominal operations and five
      patients had procedures complicated by dense adhesions. Only one injury was
      detected intraoperatively and the rest presented with uretero-vaginal fistula.
      One presented with immediate postoperative anuria. The average time interval for
      diagnosis ranged between one day and twenty-three days (average 10.7 days). The
      commonest damage was transection of the ureter. Double J stents were used in all
      repairs with two cases requiring reimplantation with psoas hitch, and two cases
      of ureteroneocystostomies and one case of primary reanastomosis. There were no
      mortality in our series.

PMID- 10968139
TI  - Epidemiology of aplastic anaemia in the state of Sabah, Malaysia.
AB  - Aplastic anaemia is a rare disease which is more prevalent in the Far East. In
      Malaysia, it appears to be unusually common in the state of Sabah. A
      retrospective analysis of all cases of aplastic anaemia diagnosed between January
      1993 and March 1996 was undertaken. The criteria of the International Aplastic
      Anaemia and Agranulocytosis Study (IAAAS) was used. In this 39 month period, 31
      cases were confirmed by marrow trephine biopsy to be aplastic anaemia. The male
      to-female ratio was 3.4. Median age of diagnosis was 23 years. There were 24
      patients (77%) who were from the Kadazan-Dusun ethnic group, which forms 18% of
      the population of Sabah. The incidence of aplastic anaemia in Sabah appears to be
      higher than that reported elsewhere in the Far East, at 4.8 per million
      population per year. Peak incidence is in the elderly group at 8.6 per million
      followed by a second peak in young people aged 15 to 24 (7.9 per million). The
      aplastic anaemia to total acute leukaemia ratio is 0.37. The marked male
      preponderance and apparent susceptibility of the Kadazan-Dusun people are also
      notable. A further prospective study to address the true incidence of aplastic
      anaemia and possible aetiologic factors accounting for these observations is
      necessary.

PMID- 10968140
TI  - Chevron osteotomy for hallux valgus--SGH experience.
AB  - Thirty-one chevron osteotomies for hallux valgus performed over a period of four
      years were reviewed. Their follow-up period ranged from one to five years. All
      the patients had pain over the bunion prior to operation. After operation, there
      was marked decrease of pain over the first matatarsophalangeal joint. The
      preoperative hallux valgus angle average 27 degrees and the postoperative angle
      averaged 12 degrees. The preoperative intermetatarsal angle averaged 13 degrees
      and the postoperative angle, 8 degrees. Ninety-one per cent of the patients were
      satisfied with the result of the procedure.

PMID- 10968141
TI  - Detection of xanthine oxidase in human plasma.
AB  - Xanthine oxidase is a highly versatile enzyme which is widely distributed among
      various species. Though the presence of the enzyme in serum is not yet
      established, high antibody titre of this enzyme has been reported. Xanthine
      oxidase is thought to be the principal source of free radical generation via
      degradation of nucleotides to the end product, uric acid. The aim of this study
      was to detect xanthine oxidase activity in human plasma and report any
      significant relationships found between its activity and variables such as race,
      age and sex for the sample size studied. Forty six normal healthy individuals (14
      males and 32 females) were studied. The enzyme activity was measured by a
      spectrophotometric method whereby the reduction of ferricytochrome c by free
      radicals was calculated and expressed as nmol O2 production/ml/min. Results
      obtained showed that there was a positive relationship between xanthine oxidase
      activity with age (r = 0.415, p < 0.05) and weight (r = 0.369, p < 0.05) in the
      normal individual. For the age group 30-39 yrs (n = 11), a higher enzyme activity
      was observed in males (2.71 +/- 1.44) as compared to females (2.34 +/- 1.23) but
      it was not significant (p = 0.53). For racial distribution, the Malays [M] have a
      higher enzyme activity (2.65 +/- 0.86, N = 32) than their Indian [I] (2.27 +/-
      0.58; N = 7) and Chinese counterparts [C] (1.44 +/- 1.22; N = 7) but this was
      also not statistically significant (M vs I: p = 0.39; M vs C: p = 0.07; I vs C: p
      = 0.16). In conclusion this study showed that there is a measurable amount of
      xanthine oxidase activity in the human plasma.

PMID- 10968142
TI  - Blood lead levels of pregnant women from the Klang Valley.
AB  - A study was conducted to compare the blood lead levels of 97 pregnant women
      warded at the Kuala Lumpur Hospital, according to their ethnicity, residence and
      place of work. The lead content of venous blood samples was determined with a
      graphic furnace atomic absorption spectrometer. Blood lead levels of Klang Valley
      women seem to have decreased from 17.3 micrograms/dl in 1982 to 7.71
      micrograms/dl in the present study most probably attributed to the phasing out of
      leaded gasoline. This level is below the 10 micrograms/dl recommended by the
      United States Environmental Protection Agency for the public, even though 27.8%
      of them still have blood lead levels that are equal to or in excess of 10
      micrograms/dl. The study shows that certain segments of the population such as
      Indians (geometric mean = 9.35 micrograms/dl) and housewives (geometric mean =
      9.55 micrograms/dl) may still experience blood lead levels that are slightly
      elevated than the rest of the population.

PMID- 10968143
TI  - Domestic accidental injuries to children presenting at a rural general practice.
AB  - A survey of domestic childhood accidental injuries was conducted at a rural
      general practice in Arau, Perlis. Data was collected from parents or other
      caregivers of 171 children, aged 12 years and below, using a pretested
      questionnaire. Male children between the ages of 6 and 12 years were the most
      common group affected, with a male to female ratio of 1.7:1. The three most
      common accidents were injuries from falls (28%), cuts, lacerations, bruises and
      puncture wounds not resulting from falls (26%), and thermal injuries (22%). The
      most commonly affected parts of the body were the limbs. Most injuries to
      children between ages 4 to 12 years occurred in the house compounds, while those
      to children below 4 years occurred in the kitchen and other locations within the
      house. Major contributing factors to the injuries were the existence of unsafe
      home environments, the risk taking activities of the children, the presence of
      hazardous products in the household and unrealistic parental attitudes to injury
      prevention.

PMID- 10968144
TI  - Clinical pathways--the new paradigm in healthcare?
AB  - A clinical pathway defines the optimal care process, sequencing and timing of
      interventions by doctors, nurses and other healthcare professionals for a
      particular diagnosis or procedure. It is a relatively new clinical process
      improvement tool that has been gaining popularity across hospitals in the USA,
      Australia and United Kingdom. Clinical pathways are developed through
      collaborative efforts of clinicians, nurses, pharmacists, physiotherapists and
      other allied healthcare professionals with the aim towards improving the quality
      of patient care. Clinical pathways have been shown to reduce unnecessary
      variation in patient care, reduce delays in discharge through more efficient
      discharge planning, and improve the cost-effectiveness of clinical services. The
      approach and objectives of clinical pathways are consistent with those of total
      quality management (TQM) and continuous quality improvement (CQI) and is
      essentially the application of these principles to the patient's bedside. This
      article examines the proliferation in the use of clinical pathways, its benefits
      to the healthcare organisation, its application as a tool for CQI activities in
      direct relation to patient care and the medico-legal implications involved.

PMID- 10968145
TI  - An outbreak of rabies in dogs in the state of Terengganu 1995-1996.
AB  - The presence of rabies in dogs has been well recognized in areas of Malaysia
      close to the Thai border but it has rarely ever been reported in Terengganu which
      is a state on the East Coast of Malaysia. From November 1995 to June 1996 six
      different rabid stray dogs were found to have been involved in dog bite attacks
      on 9 members of the public. We report these cases to highlight that rabid dog
      bites may occur even in areas where the disease is thought to be rate. Medical
      and veterinary staff must keep the possibility of the risk of rabies in mind when
      faced with patients who have been bitten by dogs.

PMID- 10968148
TI  - An unusual case of Wegener's granulomatosis.
AB  - A 35-year-old Malay man underwent treatment for uveitis of the right eye in 1992
      but developed marked visual impairment in the affected eye after he failed to
      attend follow-up. Two years later, he complained of difficulty swallowing and was
      found to have left sided X and XI cranial nerve palsies. Chest radiograph showed
      a cavitating lesion in the lower zone of the right lung field. Inflammation and
      perforation of the nasal septum was found on examination of his upper respiratory
      tract. Punch biopsies taken from that area showed chronic inflammatory change and
      necrotizing vasculities. The patient was diagnosed as having Wegener's
      granulomatosis and made a very good recovery with immunosuppressive therapy.

PMID- 10968146
TI  - Decompression illness associated with underwater logging: 6 case reports from
      Kenyir Lake, Malaysia.
AB  - The formation of Kenyir Lake as part of a hydroelectric project in the 1980s
      caused much forest area to be submerged. From 1991, underwater divers were
      employed to log these sunken trees at depths of up to 100 meters. At least 6
      mishaps involving underwater logging personnel were recorded from March 1994 to
      August 1996. We retrospectively reviewed 5 cases who were managed in Hospital
      Kuala Terengganu. The patients presented with marked cardiorespiratory and
      neurological disturbances. One diver died in the Hospital while another died at
      the recompression chamber. Three divers were treated with recompression and
      improved. Average delay before the start of recompression was 14 hours.
      Underwater logging has definite dangers and steps must be taken to ensure that
      both the divers and the equipment are appropriate for the task. Availability of a
      nearby recompression facility would greatly enhance the management of diving
      accidents, not only for commercial divers but also for recreational divers who
      frequent the islands nearby.

PMID- 10968147
TI  - Papillary adenocarcinoma of the nasopharynx--case report and review of the
      literature.
AB  - We report a rare tumour of the nasopharynx- papillary adenocarcinoma. This is
      usually of low grade and certainly in out patient it behaved so. It is even rarer
      to have this tumour in a patient with Turner's syndrome in whom there is a high
      incidence of gynaecological malignancy. It has not previously been documented and
      the occurrence in this patient is probably coincidental.

PMID- 10968149
TI  - Typhoid thyroiditis.
AB  - Acute suppurative thyroiditis in a 62 year old lady with enteric fever is
      reported. Plain radiography of the neck showed a distinct localised abscess
      cavity with air fluid level. A rare causative agent Salmonella typhi was
      isolated. Needle aspiration and antibiotics resulted in complete recovery.

PMID- 10968150
TI  - Lingual haematoma: yet another unusual cause of upper airway obstruction.
AB  - An episode of acute upper airway obstruction was caused by a lingual haematoma,
      when a patient with end stage renal failure suffered a hypocalcaemic fit and bit
      his tongue. The large haematoma and profuse bleeding caused the patient to
      obstruct and become hypoxic, and rendered laryngoscopy and intubation impossible,
      requiring an urgent tracheostomy to secure the airway.

PMID- 10968151
TI  - Neural leprosy--a case report.
AB  - Neural leprosy is rare. This is a report of a 63-year-old Indian man who had long
      standing multiple peripheral neuropathy. The slit skin smear for acid-fast
      bacilli of Mycobacterium leprae was positive. The skin and nerve biopsies were
      normal. He was treated with rifampicin, dapsone and clofazimine.

PMID- 10968152
TI  - Acute coronary syndromes. I. Recent advances in pathogenesis.
AB  - New knowledge on the pathogenesis of the acute coronary syndromes provides the
      clinician with a better understanding of these important, often life-threatening,
      events and opens up new ways of managing them. The identification of the
      vulnerable plaque whilst important and possible pathologically still requires
      elaborate and often invasive methods. The central role of inflammation and the
      platelets in these syndromes has already been translated into practical
      therapeutics. Identifying and predicting which plaque would rupture and thereby
      facilitating the formation of an acute obstructive thrombus continue as major
      challenges to the clinician, but, in the meantime, regressing and stabilising
      these plaques are achievable goals.

PMID- 10968153
TI  - Pain management and the role of pain clinics in Malaysia--is there a place for
      alternative medicine in pain clinics?

PMID- 10968154
TI  - Patterns of post-operative analgesic usage in adults and children.
AB  - There appears to be a general tendency towards under-usage of analgesics not only
      in children but also in adults. The aim of this study was to describe the pattern
      of analgesic usage in adults and children admitted for major intra-abdominal
      surgery. All patients who had intra-abdominal surgery at University Science
      Malaysia Hospital (USM Hospital) from 1st January to 31st March 1995 were
      included in the study. Children were patients of 12 years and below and adults
      were patients above 12 years of age. Data including age, sex, weight, type of
      analgesics used, the number of patients who had analgesics ordered and
      administered post-operatively were obtained from the patients' medical record. A
      total of 48 children and 67 adults were studied. Narcotic analgesics were the
      most common analgesics ordered both in adults (95.5%) and in children (97%). Post
      operative analgesics were ordered significantly more often for adults 67 (100%)
      than for children 33 (69%) (p < 0.0001). In adults, 70% of patients who had
      analgesics ordered post-operatively had their analgesics administered, but in
      children only 39.4% of patients had their analgesics administered (p < 0.001).
      The most common route of administration was intramuscular in both adults (95.5%)
      and children (88%). Analgesics were more likely to be administered in the
      intensive care units (100%) than in the surgical wards (60%) (p = 0.049).
      Elective or emergency surgery and the time of day when surgery was performed did
      not affect the frequency of analgesics ordered or administered. In summary,
      children in this hospital had less analgesics ordered and administered following
      intra-abdominal surgery compared to adults. The results of this study imply that
      increased attention should be given to relieve postoperative pain with analgesic
      drugs in children.

PMID- 10968155
TI  - Use of the uroflow study in the diagnosis of bladder outlet obstruction in
      elderly men.
AB  - The uroflow and pressure-flow data of 67 men aged 65 years or more were compared.
      At best, the uroflow study applying the Liverpool nomogram (25th percentile) and
      Bristol nomogram (OSD) diagnosed bladder outlet obstruction with sensitivity of
      62.5% and 62.5% and specificity of 48.8% and 74.4% respectively. Using the 50th
      percentile of the Liverpool nomogram as the cut-off resulted in a negative
      predictive value of 100.0% allowing about 10% of men to have this diagnosis ruled
      out. We conclude that the uroflow study is inaccurate in diagnosing bladder
      outlet obstruction in elderly men. However, it can be used to rule out this
      condition in the small subset of men with maximum flow rates above the 50th
      percentile of the Liverpool nomogram.

PMID- 10968156
TI  - Epidemiology of head injury in Malaysian children: a hospital-based study.
AB  - A prospective observational study was carried out at the Emergency Department,
      Hospital Kuala Lumpur to determine the proportion of accidental head injury among
      children and the circumstances of injury. The study was carried out from November
      1993 to January 1994 on all children below 14 years who presented to the
      Emergency Department with accidental head injury. Accidental head injury made up
      (4.75%) of all cases seen at the Casualty Department. The ratio of boys to girls
      was 2:1. The mean age of head injured children was 5.2 (S.D. 3.63) years. The
      leading cause of head injury was fall (63%) followed by road traffic accidents
      (RTA) in (30.7%) while the rest were due to 'impact' (injury caused by flying
      object or missiles) injuries. More than half (54.4%) of those injured in RTA were
      pedestrians. Pedestrian injury was particularly important in the 5-< 14 years age
      group, where adult supervision was lacking in two thirds of the children. None of
      the patients who were involved in vehicle-related injuries had used a suitable
      protective or restraining device. All three patients who died were from this
      group. This study emphasises the need for stricter enforcement of laws related to
      the use of protective devices and measures to decrease child pedestrian injury.
      The issues of lack of adult supervision, both in and outside the home need to be
      addressed.

PMID- 10968157
TI  - A 3 year case study of alcohol related psychotic disorders at Hospital Seremban.
AB  - This paper reports the characteristics and psychopathology of alcohol dependents
      with alcohol induced psychotic disorder admitted to the Seremban Hospital. The
      method is that of a case study of all alcohol dependents with alcohol induced
      psychotic disorder admitted to the Psychiatric Ward, Hospital Seremban over 3
      years (1993-1995). There were 34 subjects, 30 Indians, 3 Chinese and 1 Malay with
      a mean age of 43 years. 32 were men and predominantly of Social Class IV and V
      (91%). They had a mean duration of drinking of 14.2 years and had a mean weekly
      consumption of 69.5 units of alcohol. There was a family history of alcohol
      dependence in (44%). The majority (68%) consumed samsu with beer the second
      choice. Auditory hallucinations (26) and delusions (16) were common while visual
      hallucinations (3) and depression (2) were less frequent. Speech disorder
      occurred in 4 subjects. 2 developed delirium tremens and 1 died. Liver function
      test was normal in 55%. All except the death from delirium tremens responded to
      treatment with a combination of anxiolytics, thiamine and antipsychotics and were
      rapidly discharged. The mean stay was 7 days. However, (68%) did not return for
      follow up and only 4 were abstinent from alcohol at the time of follow up.

PMID- 10968158
TI  - Cannulation of internal jugular vein in neutral head position.
AB  - An approach to cannulate right internal jugular vein in neutral head position is
      described for situations where head rotation and extension are contraindicated.
      Venous puncture was made immediately lateral to the carotid artery at the level
      of cricoid cartilage and directed caudad. In 40 patients studied, the right
      internal jugular vein of 97.5% of the patients were successfully located by the
      finder needle. The mean (SE) number of puncture attempts to locate the vein was
      1.3 (0.1) per patient. In 72.5% (29 patients), the veins were located exactly at
      the predicted point after the first attempt. However the overall success rate for
      cannulation by the angiocath cannula was 87.5% and short term complication rate
      was 5.0%. We conclude this technique is a reliable, safe alternative for central
      venous access, especially in patients where cervical spine movement is
      contraindicated or restricted.

PMID- 10968159
TI  - Psychiatric disorders in ASEAN-migrants in Malaysia--a university hospital
      experience.
AB  - Malaysia's workforce presently includes 13% foreigners most coming from the
      neighboring ASEAN-countries. No data of the prevalence of psychiatric disorders
      amongst this population is currently available. METHOD: All patients from ASEAN
      countries admitted to the University Hospital, Kuala Lumpur between January 1994
      and June 1996 were included in a prospective study. RESULTS: During the study
      period 39 patients were admitted. Five patients were male (12.8%) and 34 female
      (87.2%). Most came from Indonesia (51.3%) and the Philippines (41.0%), while one
      each was from Brunei, Singapore and Thailand. Thirty (76.9%) were working in
      Malaysia as unskilled workers, 23 (59.0%) as maids. Six of the patients (15.4%)
      were married to Malaysians and only three (7.2%) held white-collar jobs. Three
      patients (7.2%) received the diagnosis schizophrenia and ten (25.6%) acute and
      transient psychotic disorder. Two (5.1%) were diagnosed as bipolar affective
      disorder--manic and two (5.1%) as depression without psychotic features. Five
      patients (12.8%) were depressed and had as well presence of psychotic features.
      Adjustment disorders mostly with depressed mood was diagnosed in fourteen
      (35.9%), three (7.2%) received another diagnosis. CONCLUSION: The study showed
      high rates of acute and transient psychosis as well as adjustment disorders
      indicating high stress level in this population. In particular maids from
      Indonesia and the Philippines with their dependent and isolated situation seem
      vulnerable to develop psychiatric disorders. However, overall the rates of
      psychiatric admissions (only 1.3%) in the ASEAN-nationals is relatively low and
      tends to support the view that migrants do not suffer from an excess of mental
      disorders.

PMID- 10968160
TI  - The dimensions of ocular morbidity amongst the nursing home geriatrics
      population.
AB  - A cross-sectional prevalence study amongst a nursing home elderly population was
      carried out at Rumah Sri Kenangan, Seremban, Negeri Sembilan between June 1995
      until June 1996. A total of 204 cases of 60 years and older were examined in
      order to determine the ocular morbidity amongst them. It was found that 47.5% had
      low vision and 19.1% were legally blind. Cataract was found to be the leading
      cause of low vision and blindness occurring in 81.4% and 74.3% respectively.
      Glaucoma occurred in 1% of those who had low vision and none due to macular
      degeneration or diabetic retinopathy. The magnitude of visual impairment and
      blindness in this nursing home is high but is preventable and avoidable.

PMID- 10968161
TI  - Utilisation of specialist medical manpower in Malaysia.
AB  - One hundred and twenty specialists from the Ministry of Health, the Universities
      and the private sector provided information on 4,802 patients seen over a total
      of two hundred and forty working days. This information was used to classify the
      patients into four categories based on a disease complexity classification. Each
      specialist's perception on the appropriateness of utilisation of his expertise
      was obtained. Complex cases requiring specialist expertise in management made up
      69.8%, 73.5% and 19.1% of the cases of the Ministry of Health, University and
      private sector specialists respectively. Underutilisation was most marked with
      paediatricians and obstetricians in the private sector. The Specialist Register,
      the Programme for Accreditation of Hospitals and a National Health Financing Plan
      can be used to influence positively the case-mix of specialists.

PMID- 10968162
TI  - Clinical features and associated radiological abnormalities in 54 patients with
      cavum septi pellucidi.
AB  - PURPOSE: To determine the clinical and radiological features of the patients who
      were found to have cavum septum pellucidum (CSP) on the cranial computerized
      tomographic (CT) scans. METHODS: Fifty four consecutive cases of cavum septum
      pellucidum were detected amongst 1,281 patients who underwent cranial CT scans;
      their clinical and radiological features were studied. RESULTS: Recurrent
      seizures and developmental delay were the commonest presenting symptoms seen.
      Significant neurological deficits were present in 75.9% of these cases.
      Additional cerebral abnormalities were observed in the CT scan in 76% of cases,
      the commonest being cortical atrophy, cerebral infarction and hydrocephalus.
      CONCLUSIONS: There seems to be a strong association between CSP and certain
      neurological abnormalities in the population studied. Further interpretation of
      this study would be possible if normal population in this geographical area is
      screened for CSP using cranial CT scans or magnetic resonance imaging.

PMID- 10968163
TI  - Anticardiolipin antibody isotype profile in lupus nephritis--a cross sectional
      survey.
AB  - Thirty-six patients with lupus nephritis (LN) attending the Nephrology Clinic,
      Hospital Kuala Lumpur were studied for the prevalence of anticardiolipin antibody
      (ACA) isotypes (IgG and IgM) and other associated antibodies, antinuclear
      antibody (ANA) and anti-ds DNA antibody and to determine the possible association
      between serological and clinical parameters. The study population consisted of 20
      (55.6%) Malays, 15 (41.7%) Chinese and 1 (2.8%) Indian with a mean age of 31.4 +/
      11.3 years, range 14 to 60 years. The female to male ratio was 11:1. The average
      time between diagnosis and blood sampling was 4.4 years (range 0.25 to 15 years).
      Increased ACA levels were found in 20 (55.6%) patients where raised IgG ACA and
      IgM ACA were observed in 20 (55.6%) and 2 (5.6%) cases respectively. ANA and anti
      ds DNA antibodies were detected in 22 (61.1%) and 4 (11.1%) individuals
      respectively, with the majority (82%) showing a speckled pattern of nuclear
      staining. However, neither the IgM ACA nor IgG ACA showed any significant
      association with thrombosis or any other clinical parametres. Our preliminary
      study indicates that ACA is a frequent finding in lupus nephritis and that the
      IgG isotype is more prevalent.

PMID- 10968164
TI  - A survey of hysterectomy patterns in Malaysia.
AB  - A prospective cross-sectional study involving 14 government hospitals was
      undertaken for a period of 6 months in Malaysia to study the patterns of
      hysterectomy for gynaecological indications. A total of 707 patients were
      enrolled in the study consisting of 612 abdominal hysterectomies and 95 vaginal
      hysterectomies. Fibroids (47.6%) and uterovaginal prolapse (13.4%) formed the
      main indications for surgery. The initial preoperative diagnosis was accurate in
      82.8% of cases. A different pathology from that initially suspected was noted in
      118 cases. The overall complication rate was 7.9% but vaginal hysterectomies
      carried a statistically higher complication rate compared to abdominal
      hysterectomies. Urinary tract infection was significant in vaginal
      hysterectomies. Blood transfusion was required in 25.0% of abdominal and 6.3% of
      vaginal hysterectomies. There were no laparoscopic hysterectomies or mortality in
      this series.

PMID- 10968165
TI  - Secondary intraocular lens implantation in University Hospital, Kuala Lumpur.
AB  - Secondary intraocular lens implantation after cataract surgery done in University
      Hospital between 1983 to 1993 were reviewed. Thirty three patients (37 eyes)
      underwent secondary intraocular lens implantation during this period. Twenty four
      eyes had secondary anterior chamber lens implantation while 13 had posterior
      chamber lens implantation. There was no case of secondary posterior scleral
      fixation lens implantation. Visual acuity of 6/9 or better was seen in 25 of 37
      eyes (67%) in the series. Eyes seeing as good or better than before secondary
      implantation procedure were noted in 34 of 37 eyes (92%). Vision of 6/9 or better
      was seen in 9 of 13 eyes (70%) with posterior chamber implants and 16 of 24 eyes
      in (67%) with anterior chamber lenses. Complications including bullous
      keratopathy, uveitis and glaucoma were seen with anterior chamber implants of the
      rigid type resulting in poorer visual acuity than before the secondary procedure.

PMID- 10968166
TI  - Chronic pain management--upper visceral malignancies coeliac plexus block with CT
      scanning--a case report.
AB  - Coeliac plexus block has been described more than seventy years ago and is widely
      used for chronic pain management in upper visceral malignancies. The technique
      described here is a posterior approach using CT scan guidance with absolute ethyl
      alcohol. A case illustration of a patient with carcinoma of pancreas managed with
      coeliac plexus block for pain control is presented.

PMID- 10968168
TI  - Tumoral cystitis in children.
AB  - Three children aged 3-11 years had ultrasonography of the urinary tract for the
      investigation of dysuria and haematuria. A bladder mass was seen in these 3
      children. One child had computed tomography scan, cystoscopy and bladder biopsy
      because rhabdomyosarcoma was considered. The biopsy revealed an inflammatory
      process. The urine culture of the other 2 children revealed E. coli. On
      ultrasonography, the inflammatory mass may appear homogeneously hypoechoic or may
      contain moderate level echoes. The mucosal surface of the mass may be smooth or
      lobulated. It is important to consider an infective cause for a bladder mass in
      children because computed tomography, cystoscopy and biopsy may be avoided.

PMID- 10968167
TI  - Fetal supraventricular tachycardia--a case report.
AB  - A gravid patient with fetal supraventricular tachycardia is presented. A review
      of this rare condition and the present recommended mode of therapy are discussed.

PMID- 10968169
TI  - Tuberculous retinal vasculitis.
AB  - A patient who was referred to the eye department for routine ocular assessment
      prior to commencement of antituberculous therapy was found to have periphlebitis
      in both eyes despite being visually asymptomatic. Fluorescein angiography
      confirms the presence of vasculitis without any retinal oedema or areas of non
      perfusion, which may sometimes accompany the condition. Within 2 months of
      systemic treatment, the ocular signs regressed without any permanent effect on
      vision. This case highlights a rare ocular complication associated with systemic
      tuberculosis which fortunately did not result in loss of vision due to prompt
      treatment.

PMID- 10968170
TI  - Calcified vertical plate of the cricoid--a rare pitfall in the diagnosis of an
      oesophageal foreign body.
AB  - We present a case of rare pitfall in the diagnosis of an oesophageal foreign body
      due to the calcified vertical plate of the cricoid to highlight the need to be
      aware of this entity to avoid unnecessary morbidity.

PMID- 10968171
TI  - Detection of apoptotic cells in Vero cell cultures inoculated with samples
      derived from fatal cases of Sarawak acute childhood viral infection.
AB  - Infectious agent(s) causing the fatal Sarawak acute childhood viral infection
      (SACVI) has not been identified. In the present study, results indicating that
      inocula prepared from the fatal cases of SACVI induced apoptosis in Vero cell
      cultures are presented. These findings suggest the possible involvement of
      apoptotic cellular responses in SACVI.

PMID- 10968172
TI  - Isolation and identification of human herpesvirus 7 from an infant with exanthem
      subitum.
AB  - Exanthem subitum (ES) is a common childhood exanthematous disease. In a recent
      study of ES due to human herpesvirus 6 (HHV 6), we isolated human herpesvirus 7
      (HHV 7) from the peripheral blood mononuclear cells (PBMC) of a seven month-old
      infant with typical symptoms of ES. The identity of the virus was confirmed by
      indirect immunofluorescence using HHV 7 specific monoclonal antibody and by
      amplification of the HHV 7 specific genomic sequences using the polymerase chain
      reaction (PCR). Paired serum samples from the infant showed serological
      conversion to the isolated virus. The clinical manifestations of ES in this
      infant appeared to be milder than the classical ES due to HHV 6.

PMID- 10968173
TI  - Management of Helicobacter pylori infection--a Working Party Report of the
      Malaysian Society of Gastroenterology and Hepatology.
AB  - The Working Party Report on the Management of Helicobacter pylori serves as a
      clinical practice guideline for Malaysian doctors. H. pylori is not uncommon in
      the Malaysian population. Marked racial differences and the consistently low
      prevalence rates amongst Malays are noted. The working party recommends that if
      endoscopy is to be performed, a rapid urease test should be used for diagnosis.
      Where suspicion of the infection is strong and the urease test is negative,
      histology should be performed on gastric biopsies. Culture should be used to
      monitor resistance patterns to antibiotics and regional laboratories should
      assume this responsibility. The urea breath tests are highly accurate tests for
      diagnosis of H. pylori but is as yet not widely available in Malaysia. The
      working party strongly recommends that all peptic ulcer patients infected with H.
      pylori whether active, in remission and complicated ulcers should be treated for
      the infection. Patients with low-grade gastric mucosal lymphoid tissue lymphoma
      should also be treated for H. pylori infection. It is considered advisable that
      patients on long term nonsteroidal antinflammatory drug (NSAID) treatment with a
      history of peptic ulcers or dyspepsia and patients following resection of early
      gastric cancer or those with a family history of gastric cancer should also be
      tested and treated for H. pylori. The working party recommends, as first line
      treatment a 7-day combination therapy of a proton pump inhibitor, clarithromycin
      and metronidazole or amoxicillin. High metronidazole resistance rates locally may
      adversely affect regimens containing the antibiotic. It should also be noted that
      regimens that yield lower eradication rates may result in higher long term
      expenditure.

PMID- 10968175
TI  - Critical appraisal of the medical research literature.

PMID- 10968174
TI  - Cyclosporiasis in a HIV-positive patient.

PMID- 10968176
TI  - Halovest treatment in traumatic cervical spine injury.
AB  - This is a cross-sectional study on the use of halovest appliance in the
      Orthopaedic and Traumatology Department, Kuala Lumpur Hospital from June 1993 to
      September 1996. Fifty-three patients with cervical spine injuries were treated by
      halovest stabilization. Majority of cases was caused by motor-vehicle accident;
      others were fall from height at construction sites, fall at home, hit by falling
      object and assault. The injuries were Jefferson fracture of C1, odontoid
      fractures, hangman fractures, open spinous process fracture and fracture body of
      C2, and fracture, and fracture-dislocation of the lower cervical spines. Majority
      of patients had hospital stay less than 30 days. The use of the halovest ranges
      from 4 to 16 weeks and the healing rate was 96%. Two patients of lower cervical
      spine injury had redislocation and one of them was operated. There was one case
      of non-union of type II odontoid fracture and treated by posterior fusion. Other
      complications encountered during halovest treatment were minor. They were pin
      site infection, pin-loosening, clamp loosening and neck pain or neck stiffness.
      This method of treatment enables patient to ambulate early and reduces hospital
      stay. We found that halovest is easy to apply, safe and tolerable to most of the
      patients.

PMID- 10968177
TI  - Neurological recovery following posterior decompression of spinal secondaries.
AB  - This is a retrospective study comprising 45 patients who underwent decompressive
      laminectomy due to secondary malignancy in the spine. There were 31 males and 14
      females. Two of them had no weakness, one was treated for radicular pain and the
      other for severe intractable back pain. Forty-three patients presented with
      weakness of the limb of which six patients were able to walk unaided, four with
      an aid, twenty four were unable to walk of which eleven of them were completely
      paralysed. Nineteen of the patients had urinary incontinence. Out of 10 patients
      in Frankel's D, 3 of them regained almost normal power post operatively and were
      able to walk without any aids at the time of discharge. There were 6 patients in
      Frankel's C and 2 improved. Of 17 patients in Frankel's B, 6 of them improved and
      were able to walk with walking aids. Only one out of ten patient from Frankel's A
      had showed an improvement. A total of three patients deteriorated post
      operatively and all of them presented with multiple level involvement. There was
      no change in the post operative status of the two patients who did not have
      weakness. Overall only 27% of the patient showed improvement following
      decompressive laminectomy.

PMID- 10968178
TI  - The surgical outcome of degenerative lumbar spinal stenosis.
AB  - A retrospective study was conducted to assess the surgical outcomes of
      degenerative lumbar spinal stenosis. Twenty-five patients treated with
      decompressive surgery in Hospital Kuala Lumpur between January 1992 and August
      1996 were reviewed. There were seven males and eighteen females. The average age
      was 51 years old (range 33 to 64 years old). The diagnosis of degenerative spinal
      stenosis was made based on the clinical features and was confirmed by
      radiographic findings. Ninety two percent of the patients had moderate to severe
      symptoms preoperatively. The types of surgery consisted of laminectomy (n = 15),
      laminotomy (n = 10), and laminoplasty (n = 1). The surgical outcomes were
      assessed based on patients' own assessment of symptoms relieved and functional
      returned to daily activities at least six months after the surgery. The average
      follow-up period was fifteen months (range 6 months to 42 months). Of these
      twenty-five patients, 4 (16%) claimed to have excellent results, 11 (44%) had
      good results, 8 (32%) reported fair, and 2 (8%) judged their surgical treatment
      as poor with little or no use. There was no anaesthetic, cardiovascular, or
      thromboembolic complications seen in this study. Four patients had recurrent
      claudication, one demonstrated localised arachnoiditis, and two had lumbar
      instability which were not documented preoperatively. One patient had L4 nerve
      root avulsion with dura torn and another patient had superficial wound infection.
      We concluded in this study that decompressive surgery offers satisfactory results
      in patients with moderate to severe degenerative spinal stenosis in short term
      follow-up.

PMID- 10968179
TI  - Conservative management of femoral shaft fractures in children.
AB  - Thirty-two children with femoral shaft fractures were treated conservatively with
      initial skin traction followed by an additional period in a spica cast. After 12
      to 20 months of follow up, none had any pain and all of them were attending
      school without problems. Shortening of more than 2 cm occurred in 6 (19%) of the
      32 patients. The most important factor associated with shortening was an overlap
      of more than 2 cm of shortening of the fracture ends at the time of cast fitting.
      The average compensatory overgrowth at final assessment was 7 mm. Angular
      deformity did not pose a problem. This is a safe, simple and practical method to
      treat childhood femoral shaft fractures.

PMID- 10968180
TI  - Closed tibia fracture. "The effect of an intact fibula and the location of tibia
      fracture on fracture union".
AB  - Tibial fractures are common and complications occur more frequently than any
      other long bone fractures. The effect of fibula and location of fracture on union
      of Tibia fracture remain controversial. A retrospective study of unilateral
      closed tibial shaft fractures without any associated injury was done. From 1988
      to 1992, 74 out of 103 patients were available for the study. There were 60 males
      and 14 females with the age ranges from 3 to 75 years with an average of 29.7
      years. The differences of fractures healing were analyses with respect to the
      status of the fibula and the location of the tibial fracture. This study
      concludes that the location of the fracture and the status of the fibula have no
      significant influence on healing (p > 0.05).

PMID- 10968181
TI  - The results of surgical treatment of tibial plateau fractures.
AB  - Thirty-eight tibial plateau fractures were treated with open reduction and
      internal fixation. The fractures were classified into six groups (Hohl's 1991
      Classification) and the clinical results were evaluated using the Rasmussen
      (1973) criteria. The average follow-up period was 2.07 years. Overall there was
      one excellent, thirty-four (34) good, three fair and no poor results. In three
      patients with less than a good score there were other associated ipsilateral
      injuries and delayed mobilisation of the knee joint. There was no direct
      association between the type of internal fixation and the end result.

PMID- 10968182
TI  - Contributing factors in non-union of the humeral shaft fracture and the results
      of treatments.
AB  - Out of 218 fractures of humeral shaft treated in the department, 23 (10.5%) of
      them developed non-union. 14/23 (60.9%) fracture were located in middle third.
      Transverse (52.2%), short oblique (17.4%) and comminuted fracture (13.0%)
      constituted about 82% of all initial fracture pattern. Twelve cases (52.5%) were
      initially treated with hanging cast. Radial nerve palsy occurred in 4/23 (17.4%)
      of patient and all of them located at lower third of humerus and only one
      recovered after eight weeks of injury. Factors such as middle third comminuted
      opened fractures, soft tissue interposition, improper immobilization and poor
      patient compliance were found to be directly associated with the non-union. All
      non-unions healed following plating and bone grafting. Overall 17/23 patient
      (74%) had good results, 4/23 (17%) fair and 2/23 (9%) with poor functional
      results.

PMID- 10968183
TI  - Displaced supracondylar fracture of humerus in children--comparative study of the
      result of closed and open reduction.
AB  - The displaced supracondylar fracture of the humerus in children (Gartland type 3)
      is a most challenging injury to treat. There is controversy regarding the initial
      treatment either closed manipulation and splint immobilization or open reduction
      and internal fixation. This is a retrospective study comparing two groups of
      patients with displaced supracondylar fracture of the humerus (Gattland 3)
      treated in the Orthopaedic Unit, Universiti Kebangsaan Malaysia. The first group,
      13 patients treated with closed reduction and splint immobilization and a second
      group, 15 patients treated with open reduction and internal fixation as initial
      definitive treatment. The results showed a high failure rate of closed reduction
      and splint immobilization. This was due to difficulty in reduction, loss of
      reduction post operatively or during follow-up. Open reduction and internal
      fixation was more advantages with reduced hospitalization time, fewer
      complications, more stable fixation and better anatomical reduction with minimal
      complications for type 3 supracondylar fracture of humerus. We would recommend
      that all Gartland 3 supracondylar fracture of the humerus be treated with open
      reduction and two K-wire fixation.

PMID- 10968184
TI  - The results of treatment of dislocation and fracture--dislocation of the elbow--a
      review of 41 patients.
AB  - Forty-one patients with 42 elbow dislocations, of which 13 had acute simple
      dislocations, 21 had fracture-dislocations and 8 had neglected elbow
      dislocations, were evaluated with regard to limitation of motion, pain,
      instability and residual neurovascular deficit. All patients with acute simple
      dislocation were treated with closed reduction, but the duration of
      immobilization before commencement of active motion varied. Open-reduction was
      indicated for failed closed reduction and neglected-dislocations. Internal
      fixation as a primary procedure was only performed for displaced fracture
      dislocation. Excision of radial head or tricepsplasty were performed if the
      reduction was impossible in neglected elbow dislocation. Despite a good results
      in acute simple dislocation, 33.07% had flexion contracture of between 5 to 30
      degrees. In fracture dislocation, satisfactory results were seen in whom the
      elbow was immobilized for three weeks or less. Neglected-dislocation is
      associated with poor functional outcome, 37.5% were good and 62.5% were poor.
      Prolonged immobilization after injury was strongly associated with an
      unsatisfactory result. The results indicate that early properly supervised active
      motion is a key factor in the rehabilitation of elbow dislocation.

PMID- 10968185
TI  - Surgical treatment of acromio-clavicular dislocation.
AB  - Acromio-clavicular joint (ACJ) dislocation usually occurs in young adults
      following trauma or sports injury. Fourteen patients underwent surgical treatment
      for symptomatic total ACJ dislocation (Rockwood and Matsen Type III-VI) in our
      unit between January 1996 and June 1997. Eight patients were operated within
      three weeks of injury and six in the chronic period (after three weeks). In the
      acute group, two patients had Botsworth procedure and six had Weaver-Dunn
      operations. All six in the chronic group had Rockwood procedure. Nine patients
      achieved excellent outcome with full range of shoulder movement, pain free and
      return to work within three months of surgery. Two patients had good outcome.
      Three other patients had satisfactory outcome with tolerable pain and light duty
      at three months. Two patients developed chronic shoulder pain and one had painful
      hypertrophic surgical scar. Two patients had screw breakage requiring revision
      surgery. In conclusion, surgical treatment for ACJ dislocation produces good
      results. We suggest that surgical treatment be the treatment of choice for young
      patients requiring early recovery and good shoulder function.

PMID- 10968186
TI  - Reconstruction of lower leg defects using a medial island fasciocutaneous flap.
AB  - It is usually a major task providing soft tissue cover to significant defects of
      the lower leg. A wide variety of flaps and techniques are available, each with
      its advantages and limitations. Previously described anatomic study of the
      septocutaneous vessels of the leg have indicated a consistent lower most
      perforator at 9-12 cm from the tip of the medial malleolus. An island
      fasciocutaneous flap based on this perforator vessels can be raised subfascially.
      After the vessels have been dissected clean down to the posterior tibial artery,
      it can be rotated up to 180 degrees degrees. Successful soft tissue
      reconstruction was achieved in 18 patients. Most of the tissue loss was due to
      trauma and were around the ankle and the heel. There were 7 minor complications
      which resolved completely after 2 months. Its simplicity of design and elevation
      plus its extensive arc of rotation makes it a reliable and versatile flap in the
      reconstruction of lower leg defects.

PMID- 10968187
TI  - A review of haematogenous osteomyelitis in children in Kuala Lumpur Hospital.
AB  - We review 81 cases of acute haematogenous osteomyelitis from 1983 to 1990 to
      establish current pattern of clinical presentation, modes of treatment and
      success of therapy. Majority of the patient (70%) presented within a week of
      symptom and significant number of them came with fever and swelling of the
      affected limb. Sedimentation rate was found to be raised in all of them. Fifty
      four (55%) of them were treated surgically. The average antibiotic time was one
      week by intravenous administration followed by additional oral therapy for period
      up to four weeks. Average follow-up was 9 months. Six of them (7.5%) end up with
      various complication which was believed to be due to delay in getting medical
      treatment.

PMID- 10968188
TI  - An epidemiological study of septic arthritis in Kuala Lumpur Hospital.
AB  - Forty-one patients with 42 joint infections were admitted to the hospital between
      June 1989 and June 1994. An overview on the behaviour of septic arthritis in both
      children and adults, at presentation and after various types of treatment was
      done. There were 32 knees, 7 hips, 2 elbows and 1 shoulder. Duration of symptoms,
      type of organism, type of joint drainage, presence of preexisting joint problems
      and presence of osteomyelitis are among the important factors with prognostic
      significance. Seventy three percent of patients with less than 7 days duration of
      symptoms had satisfactory results. Whereas when the duration of symptoms exceeded
      7 days, 75% of the patients had unsatisfactory outcome. All cases with poor
      outcome had positive cultures. Staphylococcus aureus was responsible for 77% of
      the culture-positive cases. All Staphylococcus aureus in this study were
      penicillin-resistant but sensitive to cloxacillin. There were 3 instances where
      Staphylococcus became resistant to cloxacillin following recurrence of septic
      arthritis. However, they were still sensitive to third generation cephalosporin.
      Staphylococcus aureus was capable of producing poor results even when the case
      was treated early. Other organisms were gram-negative bacilli which infect
      patients with suppressed immune system, that is, intravenous drug abuser,
      systemic steroid therapy and diabetes mellitus. Open arthrotomy was the method of
      drainage used in all hip sepsis. This method was also the most reliable method of
      joint drainage in other joints compared to aspiration method when frank pus was
      already present. Most immuno-compromised patients recovered badly from septic
      arthritis. Associated adjacent osteomyelitis, preexisting chronic arthritis and
      recent intra-articular fractures were also noted to adversely affect the
      functional outcome.

PMID- 10968189
TI  - The management of psoas abscess.
AB  - The presentation and management of psoas abscess was studied prospectively in 5
      patients and retrospectively in 4. 3 patients had bilateral abscesses. All
      patients had back pain and a mass in loin or iliac fossa. 7 patients had no hip
      findings. One patient had a perinephric abscess and another had radiological
      features of tuberculosis of the spine. In the other seven no cause for the
      abscess could be identified. Ultrasonography demonstrated the abscess in all
      patients; CT scanning done in 5 patients was confirmatory. Drainage was done by
      an extraperitoneal route. Biopsy of the abscess wall in 2 patients demonstrated
      tuberculosis. They, the patient with TB spine and 3 others put empirically on
      anti-tuberculosis chemotherapy responded well. The perinephric abscess grew
      Pseudomonas sensitive to gentamycin, but she and two other patients died due to
      multiorgan failure.

PMID- 10968190
TI  - Arthroscopy under local anaesthesia.
AB  - We studied 95 patients who underwent knee Arthroscopy under local anaesthesia
      between JANUARY 1995 till 1997. Materials used were 1% Xylocaine and 0.25%
      Bupivacaine of 20 mls each combined with midazolam 2 mg and IV pethidine 30 mgm
      for sedation. The patients were attached to monitors (pulse Oxymeter, ECG and BP
      and pulse recorders) and blood less field was created using a tornquet. The
      procedures lasted about 45 minutes. 90 out of 95 patients completed the
      procedures successfully without any complications. 2 developed respiratory
      embarrassments and were intubated and ventilated. 3 procedures abandoned and
      converted to general anaesthesia. The range of procedures done include
      meniscectomy, meniscal repair, synovial biopsy, debridement for osteoarthrosis,
      shaving of osteophytes, drilling of cartilage and bones and removal of loose
      bodies. This study is to show that knee arthroscopy under LA is a safe
      alternative in hospitals where GA time is limited.

PMID- 10968191
TI  - Simultaneous bilateral total knee replacement.
AB  - This paper summarises our experience of twenty one patients with degenerative
      arthritis treated by bilateral simultaneous total knee replacement (BSTKR) in
      Tawakal Hospital in a period of twenty two months vis. January 1994 to November
      1995. The results were analysed according to the scoring system of Hospital for
      Special Surgery. The preliminary observations were encouraging, 90% excellent, 8%
      good and 2% fair results. The benefits, safety and cost effectiveness of the
      procedure as compared to the unilateral staged knee replacement are discussed. We
      recommend that BSTKR be routinely practised for appropriate situations in all
      institutions where the expertise and facilities are available.

PMID- 10968192
TI  - Anterior cruciate ligament reconstruction using the patellar ligament.
AB  - From January 1992 to January 1996, thirty-three patients with persistent clinical
      and functional knee instability due to anterior cruciate insufficiency underwent
      ACL reconstruction using central third of the bone-patellar ligament-bone graft.
      An early experience was presented with average follow-up of 9.8 months (range six
      to thirty-three months). There thirty-two male and two females. The average age
      was twenty-four months. Eighty-three percent were involved in football injury.
      The average time interval from initial injury to operation was twenty-five
      months. Majority presented with knee pain and giving way. Meniscal tear was the
      commonest associated injury in more than 70 percent; the lateral meniscus being
      more frequently injured (42 percent) than the medial meniscus (15 percent). Using
      modified criteria by Paterson and Trickey (1986), nine patients (27 percent) had
      good results and twenty-two (67 percent) has satisfactory results. Two patients
      (6 percent) who had post-operative infection were graded as poor. Functional
      stability was achieved in twenty-eight (85 percent) and instability persisted in
      five (15 percent). There were marked clinical improvement in the Lachman and
      anterior drawer grading post-operatively. The accelerated rehabilitation
      programme was effective in obtaining early clinical improvement and in reducing
      post-operative knee stiffness.

PMID- 10968193
TI  - Residual deformity following surgical treatment of congenital talipes
      equinovarus.
AB  - A study was carried out on 24 patients (36 clubfeet) surgically treated at the
      Orthopaedic Department National University of Malaysia, Kuala Lumpur, over a
      period of four and half years. Nine feet underwent posterior release, 24 feet
      underwent posteromedial release combined with Evan's procedure. The overall
      operative result was 63.3% good, 9.5% fairly and 27.2% poor. Patients who
      underwent surgery between 3 to 12 months showed a high percentage of good results
      (66.7%). Metatarsal adduction was found to be the commonest residual deformity
      (63.9%), followed by heel varus (11.1%), cavus (11.1%) and equinus (5.6%).
      Inadequacy of primary surgery and post operative period of immobilization
      resulted in a significant high failure rate.

PMID- 10968194
TI  - Hand replantation and revascularization--six years experience in Hospital Kuala
      Lumpur 1990-1995.
AB  - A retrospective study was conducted in 130 patients who underwent replantation or
      revascularization of 195 amputations in Hand and Microsurgery Unit Hospital Kuala
      Lumpur from 1990 to 1995. There were 130 patients with 195 amputations in the
      duration of 6 years study, which were mainly males (111 patients, 85.4%). The
      commonest age group involved was 19-25 years old (49 cases, 63.7%). There were
      146 complete amputations replanted and 49 cases of incomplete amputations were
      revascularized. The commonest part involved was thumb and index finger (23% of
      cases each) and majority was caused by industrial accident (60.8%). However in
      pediatric age group home accident was the leading cause of the amputation
      (93.8%). The overall survival rate for the amputation was 65.6%.
      Revascularization had a better survival rate (77.6%) than replantation (61.6%). A
      clean cut wound and ischaemic time less than 12 hours gave better survival rate.
      However, there was no significant different chance of survival on distribution of
      injured parts and ischaemic time (< 12 hours).

PMID- 10968195
TI  - Arterial fibrodysplasia in the hand.

PMID- 10968196
TI  - The calcium channel blocker controversy.
AB  - A major controversy about the safety of calcium channel blockers (CCBs) has
      arisen since the publication of a case-control study showing that hypertensives
      who suffered an acute myocardial infarction (MI) were more likely than
      hypertensives who had not had an MI to be taking one of these (short-acting)
      agents than other antihypertensive agents. This study was accompanied by a
      republication of older studies showing that large doses of short-acting
      nifedipine given to post-MI patients increased their mortality rate. The danger
      of massive doses of short-acting nifedipine in a post-MI patient is real but
      irrelevant to current practice. On the other hand, the putative dangers of short
      acting CCBs in the treatment of hypertension do not apply to the current use of
      long-acting CCBs. Therefore the scare over their use is both irrational and
      unfortunate.

PMID- 10968197
TI  - Induction of high affinity epidermal growth factor binding in the aorta of Dahl
      hypertensive rats fed with high salt diet.
AB  - Dahl salt sensitive rats (DS) developed severe hypertension on four weeks of high
      salt feeding while the Dahl salt resistant rats (DR) remained normotensive under
      the same conditions. The specific maximal binding of epidermal growth factor
      (EGF) in the freshly prepared kidney membranes of high salt fed DS rats was
      higher than those from DR rats (5.3 +/- 1.9 vs. 1.6 +/- 0.62 fmoles/mg protein,
      p<0.001). Scatchard analysis of EGF binding in the kidney showed one class of
      receptors in the DR (K(d) = 0.75 +/- 0.05 nM) as well as in the DS rats
      (K(d)=0.69 +/- 0.06 nM). The EGF binding in the aortic membranes of DS rats was
      also high compared to DR rats (24.98 +/- 5.52 vs. 13.20 +/- 4.10 fmoles/mg
      protein, p < 0.001). Scatchard analysis of EGF binding in the aorta showed one
      class of receptors in the DR aorta with a K(d) of 0.70 +/- 0.06 nM. On the other
      hand, in the DS rat aorta two classes of receptors, a high affinity form
      (K(d)=0.05 +/- 0.01 nM) and a low affinity form (K(d)=3.5 +/- 0.3 nM) were noted.
      The induction of a high affinity species of EGF receptors in the aorta, appears
      to be a mechanism unique to the salt fed DS rats.

PMID- 10968198
TI  - Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously
      hypertensive rats (SHRSP).
AB  - Noradrenergic (NA) nerve fiber density was investigated in the subepicardium and
      myocardium of ventricles in stroke-prone spontaneously hypertensive rats (SHRSP)
      and was compared with that of normotensive Wistar Kyoto (WKY) rats. Fluorescent
      NA nerve fibers in the subepicardium of the right and left ventricles of both
      strains at the ages of 10, 30, 60, 90, and 180 days were examined by the
      glyoxylic acid method. NA nerve fibers in the myocardium of the right and left
      ventricles and the ventricular septum of both strains at the ages of 30, 90, and
      180 days were also examined in a similar manner. The density of NA nerve fibers
      was measured by quantitative image analysis. The distribution pattern of NA nerve
      fibers in the entire subepicardium of ventricles of both strains showed a
      meshwork pattern throughout the examination period. In sections of the
      myocardium, NA nerve fibers were distributed between heart muscle cells and
      around blood vessels in both strains at all ages examined. The densities of NA
      nerve fibers in the subepicardium of the ventricles of SHRSP were significantly
      higher than those of WKY rats at all ages examined except for the subepicardium
      of the left ventricle at 90 days of age. The densities in the myocardium of the
      right ventricle in 30- and 90-day-old SHRSP were significantly higher than those
      in WKY rats. The ratios of NA nerve fiber density of SHRSP to that of WKY rats
      were greater in the subepicardium of the right and left ventricles, except at 90
      days of age, and in the myocardium of the right ventricle of younger animals as
      compared with older ones. NA hyperinnervation in the subepicardium and myocardium
      of the ventricles of SHRSP may be a primary change of the heart before the onset
      of hypertension and may be caused by hyperfunction of the stellate ganglia.

PMID- 10968199
TI  - Comparison of the antihypertensive effects of the new angiotensin II (AT1)
      receptor antagonist candesartan cilexetil (TCV-116) and the angiotensin
      converting enzyme inhibitor enalapril in rats.
AB  - Antihypertensive effects of an angiotensin (Ang) II receptor antagonist,
      candesartan cilexetil (TCV-116), were compared with those of an angiotensin
      converting enzyme (ACE) inhibitor, enalapril, in spontaneously hypertensive rats
      (SHR), 2-kidney, 1-clip hypertensive rats (2K, 1C-HR) and 1-kidney, 1-clip
      hypertensive rats (1K, 1C-HR). CV-11974, the active form of TCV-116, had no
      inhibitory activity for plasma ACE. In rats, TCV-116 inhibited the pressor
      responses to Ang I, Ang II, and Ang III without an effect on the bradykinin (BK)
      induced depressor response. Enalapril inhibited only the Ang I-response and
      potentiated the BK-response. In SHR, the antihypertensive effect of TCV-116 (10
      mg/kg) was larger than the maximum antihypertensive effect of enalapril and was
      not intensified by combination with enalapril. Administration of CV-11974
      potentiated the maximum antihypertensive effect of enalapril. Although both
      agents reduced blood pressure in 2K, 1C-HR, only TCV-116 had a marked
      antihypertensive effect in 1K, 1C-HR. These findings indicate that TCV-116 is
      more effective than enalapril in reducing blood pressure in SHR and 1K, 1C-HR,
      and that the BK- and/or prostaglandin-potentiating effect of enalapril
      contributes little to its antihypertensive mechanism in SHR.

PMID- 10968200
TI  - Sexual dimorphism of renal alpha2-adrenergic receptor regulation in Dahl rats.
AB  - Male Dahl salt-sensitive hypertensive (S) rats develop hypertension faster than
      females. We measured renal alpha2-adrenergic receptor density of inbred Dahl salt
      sensitive (SS/JR) and salt-resistant (SR/JR) rats, using [3H]-rauwolscine
      saturation binding studies. Male and female SS/JR rats were gonadectomized or
      sham-operated at 6 weeks of age and fed a high salt diet for 4 weeks. Additional
      intact SS/JR and SR/JR rats of both sexes were fed the high salt diet for a
      longer period of time (7 weeks instead of 4 weeks). Both blood pressure and renal
      alpha2-adrenergic receptor density were significantly higher in male than female
      SS/JR rats on high salt diet for 4 weeks. Gonadectomy did not change blood
      pressure nor did it change renal alpha2-adrenergic receptor density measured at
      the 4th week of high salt feeding in either male or female SS/JR rats. When the
      SS/JR rats were fed high salt diet for a longer period (for 7 weeks), blood
      pressure of female SS/JR reached the level of males, but the density of renal
      alpha2-adrenergic receptors was still significantly lower than that of males.
      Both renal alpha2-adrenergic receptor density and blood pressure were higher in
      male than female SR/JR. We conclude that higher blood pressure in male Dahl SS/JR
      and SR/JR rats is associated with higher renal alpha2-adrenergic receptor density
      compared with their female counterparts.

PMID- 10968201
TI  - Effect of erythropoietin treatment on blood pressure and intracellular cation
      concentrations in maintenance hemodialysis patients.
AB  - To assess the effect of recombinant human erythropoietin (EPO) on the factors
      regulating blood pressure (BP), we determined the hemoglobin level (Hgb), blood
      viscosity (BV), plasma renin activity (PRA), plasma concentrations of aldosterone
      (PAC), adrenaline (Ad), noradrenaline (NAd), and atrial natriuretic peptide
      (ANP), and serum and intracellular concentrations of cations before and after 3
      months of EPO treatment (40 units/kg/week of EPO intravenously after each
      hemodialysis session) in 11 patients undergoing maintenance hemodialysis.
      Intracellular sodium concentration ([Na+]i) was measured using erythrocytes with
      flame photometry. EPO treatment was associated with significant increases in Hgb
      (7.1 +/- 1.4 to 8.4 +/- 1.8 g/dl, p<0.01), mean BP (103 +/- 11.4 to 116 +/- 19.9
      mmHg, p<0.01), [Na+]i (4.99 +/- 0.78 to 6.22 +/- 0.96 mmol/l, p<0.01) and BV
      (1.39 +/- 0.14 to 1.53 +/- 0.18 c.p., p<0.05), but no significant alteration in
      PRA, PAC, Ad, NAd, ANP, or in the serum concentration of Na+, K+, and Ca2+. The
      changes in mean BP (deltaMBP) were significantly correlated with delta[Na+]i
      (R=0.676, p=0.022) and deltaBV (R=0.668, p=0.034), but not with deltaHgb. By
      multiple regression analysis, delta[Na+]q and deltaBV independently contributed
      to deltaMBP; deltaMBP=2.27 X delta[Na+]i+32.2 X deltaBV +3.37 (R=0.695). These
      data suggest that intracellular sodium accumulation as well as increased blood
      viscosity may be independently involved in the blood pressure elevation after EPO
      treatment in patients under maintenance hemodialysis. We found no evidence
      supporting a role of circulating hormonal factors, such as the renin-angiotensin
      system, adrenaline, or ANP, in the change in blood pressure.

PMID- 10968202
TI  - Antihypertensive therapy reduces increased plasma levels of adrenomedullin and
      brain natriuretic peptide concomitant with regression of left ventricular
      hypertrophy in a patient with malignant hypertension.
AB  - We investigated the potential role of increased plasma adrenomedullin and brain
      natriuretic peptide (BNP) levels in a patient with malignant hypertension. A 51
      year-old man was admitted to our hospital with a chief complaint of visual
      disturbance. His blood pressure was 270/160 mmHg on admission. Papillary edema
      associated with retinal bleeding was observed. Echocardiography revealed marked
      concentric left ventricular hypertrophy with mild systolic dysfunction. Plasma
      levels of adrenomedullin and BNP were markedly elevated. Antihypertensive therapy
      reduced the plasma levels of adrenomedullin in association with a concomitant
      decrease in blood pressure. The plasma level of BNP also decreased and regression
      of left ventricular hypertrophy and normalization of left ventricular systolic
      function were observed. Our findings suggest that adrenomedullin may be involved
      in the defense mechanism against further elevations in blood pressure in patients
      with hypertension and that the plasma level of BNP may reflect left ventricular
      systolic dysfunction, left ventricular hypertrophy, or both, in patients with
      severe hypertension.

PMID- 10968203
TI  - Intracellular calcium stores and oscillatory contractions in arteries from
      genetically hypertensive rats.
AB  - Strips of tail artery from stroke-prone spontaneously hypertensive rats (SHRSP),
      but not from normotensive Wistar Kyoto (WKY) rats, exhibit oscillatory activity
      after stimulation with norepinephrine. In addition, oscillatory activity is
      observed in response to tetraethylammonium (TEA) in vessels from both SHRSP and
      WKY rats. Mechanistically, the oscillatory contractions are associated with
      calcium (Ca2+)-driven action potentials. We have tested the hypothesis that
      intracellular Ca2+ stores participate in the generation of norepinephrine-induced
      oscillatory contractions in tail arteries from SHRSP. Additionally, the role of
      intracellular Ca2+ stores on TEA-induced contractions were evaluated. Contractile
      force in strips of tail artery from SHRSP and WKY rats was measured, using
      standard muscle bath procedures, and the effect of interventions that affect the
      storage of intracellular Ca2+ on the oscillatory contractions was evaluated.
      Depletion of intracellular Ca2+ stores, with ryanodine, or inhibition of Ca2+
      uptake into the sarcoplasmic reticulum (SR), with thapsigargin and cyclopiazonic
      acid (CPA), did not inhibit oscillatory contractions induced by norepinephrine in
      SHRSP vessels. However, these agents inhibited the amplitude of TEA-induced
      contractions in WKY strips. Bay K 8644 and A23187 inhibited TEA-induced
      oscillatory contractions in WKY vessels. In SHRSP tail artery Bay K 8644
      inhibited both norepinephrine and TEA-induced contractions, while A23187 did not
      have any effect. The phospholipase C inhibitor, NCDC (3X 10(-5) M), blocked
      oscillatory activity induced by norepinephrine in SHRSP tail artery and TEA
      induced oscillations both in SHRSP and WKY vessels. These observations suggest
      that Ca2+ release and Ca2+ uptake into intracellular Ca2+ stores are not involved
      in the contraction-relaxation cycles that characterize norepinephrine-induced
      oscillatory activity in SHRSP tail artery. Similarly, SR Ca2+ stores may modulate
      but are not essential for TEA-induced oscillatory contractions.

PMID- 10968204
TI  - Inhibition by adrenomedullin of arginine vasopressin-activated mitogen-activated
      protein kinase in rat glomerular mesangial cells via cAMP production.
AB  - The present study was undertaken to determine whether adrenomedullin modulates
      the arginine vasopressin (AVP)-activated mitogen-activated protein (MAP) kinase
      in cultured rat glomerular mesangial cells. AVP dose-dependently increased
      cellular free calcium, and this increase was unaffected by adrenomedullin.
      Adrenomedullin increased cellular cAMP production in a dose-dependent manner and
      AVP activated MAP kinase in a dose-dependent manner. When cells were preincubated
      for 15 min with adrenomedullin at concentrations of 1 X 10(-8) M or higher, the
      AVP-activated MAP kinase was significantly reduced. In addition, the activation
      of MAP kinase by phorbol-12-myristate-13-acetate (PMA) was significantly
      inhibited by adrenomedullin. Similarly, forskolin also diminished the activation
      of MAP kinase by AVP and PMA. The inhibition by adrenomedullin or forskolin of
      AVP-activated MAP kinase disappeared when cells were preexposed to H-89, an
      inhibitor of protein kinase A. These results indicate that adrenomedullin
      inhibits the AVP activation of MAP kinase mediated through cAMP in glomerular
      mesangial cells and that the site of action of adrenomedullin is behind the site
      of activation of protein kinase C.

PMID- 10968205
TI  - Endothelin-1 and vasopressin signalling in blood vessels of young SHR in
      comparison to adult SHR.
AB  - To examine potential intracellular signalling abnormalities of endothelin-1 (ET
      1) and vasopressin (AVP) which may contribute to blood pressure elevation,
      contractility and inositol phosphate levels in intact arteries and calcium
      transients in vascular smooth muscle cells were investigated after stimulation
      with these peptides in pre-hypertensive 5 week-old spontaneously hypertensive
      rats (SHR) and age-matched Wistar-Kyoto (WKY) rats. Contractility of aorta in
      response to ET-1, AVP and norepinephrine (NE) was blunted in SHR relative to WKY.
      Contraction of mesenteric resistance arteries induced by ET-1 was similar in both
      groups, whereas sensitivity in response to NE and AVP was greater in SHR. Basal
      inositol phosphate in aorta and mesenteric arteries was elevated in SHR, but ET-1
      and AVP-stimulated inositol phosphate responses were similar in both groups.
      Calcium transients induced by ET-1 and AVP in vascular smooth muscle cells were
      similar in young SHR and WKY. In contrast, in adult rats inositol phosphate
      responses to ET-1 were blunted in aorta of SHR, but were normal in mesenteric
      arteries. Inositol phosphate responses to AVP were similar in both rat strains of
      rats both in aorta and mesenteric arteries except for accumulation of inositol
      trisphosphate, which was enhanced in mesenteric arteries of SHR. Calcium
      mobilization in vascular smooth muscle cells from adult SHR also exhibited
      enhanced responses to AVP. In conclusion, in young SHR, blunted ET-1 and AVP
      induced contraction in aorta and enhanced AVP-induced mesenteric artery
      contraction are associated with normal inositol phosphate production and calcium
      mobilization. Signal transduction in response to ET-1 and AVP is depressed in
      aorta of pre-hypertensive SHR after the step of inositol phosphate generation and
      calcium mobilization. Resistance vessel reactivity to AVP is enhanced in young
      SHR at steps following inositol phosphate generation and calcium mobilization.
      These results argue against a role of ET-1, but suggest the possible involvement
      of AVP in the development of this model of genetic hypertension.

PMID- 10968207
TI  - 1H NMR studies: dynamics of water in gelatin.
AB  - Proton magnetic resonance was used to characterize the dynamics of water in
      gelatin. Both sol and gel states were investigated. Transverse relaxation rates
      (R2) were dependent on the proton frequency measurement. (R2) measured with the
      Carr-Purcell-Meiboom-Gill pulse sequence was dependent on pulse spacing. These
      observations were interpreted in terms of chemical exchanges between water
      protons and those of the macromolecules in the sol state, whereas in the gel
      state the contribution of diffusion through microheterogeneities in the sample
      seems to provide an additional transverse relaxation mechanism.

PMID- 10968206
TI  - Clinical significance of pressor responses to laboratory stressor testing in
      hypertension.
AB  - We investigated the relation between pressor responses to laboratory stressors
      and 24-hour blood pressure (BP) variability or left ventricular mass. Mental
      arithmetic tests, isometric hand grip exercise, and bicycle ergometer exercise
      were carried out in middle-aged normotensive subjects (n=10) and in age-matched
      WHO stage I (n=23) and stage II (n=11) patients with essential hypertension.
      Mental arithmetic was associated with a greater rate of increase in plasma
      epinephrine than in norepinephrine, and handgrip exercise was associated with a
      greater rate of increase in plasma norepinephrine than in epinephrine in all
      three groups. Bicycle ergometer exercise caused a remarkable increase in plasma
      norepinephrine and a mild increase in plasma epinephrine in all three groups. In
      mental arithmetic tests, pressor responses of hypertensive patients were
      significantly greater than those of normotensives. The pressor response during
      mental tests was significantly correlated with the value of 24-hour BP
      variability in all subjects (r=0.56, p< 0.01). The pressor response to handgrip
      increased with the stage of hypertension. A good correlation existed between the
      pressor response to handgrip and the left ventricular mass index in the subjects
      (r=0.73, p < 0.001). There was no difference in the pressor response to ergometer
      exercise between any of the groups. The findings suggest that the pressor
      response to mental stress reflects BP variability and that the response to
      handgrip is correlated with target-organ disease associated with hypertension,
      especially the degree of cardiac hypertrophy.

PMID- 10968208
TI  - Osmotic water permeability measurements using confocal laser scanning microscopy.
AB  - We have developed a method for measurement of plasma membrane water permeability
      (P(f)) in intact cells using laser scanning confocal microscopy. The method is
      based on confocal recording of the fluorescence intensity emitted by calcein
      loaded adherent cells during osmotic shock. P(f) is calculated as a function of
      the time constant in the fluorescence intensity change, the cell surface-to
      volume ratio and the fractional content of the osmotically active cell volume.
      The method has been applied to the measurement of water permeability in MDCK
      cells. The cells behaved as linear osmometers in the interval from 100 to 350
      mosM. About 57% of the total cell volume was found to be osmotically inactive.
      Water movement across the plasma membrane in intact MDCK cells was highly
      temperature dependent. HgCl2 had no effect on water permeability, while
      amphotericin B and DMSO significantly increased P(f) values. The water
      permeability in MDCK cells transfected with aquaporin 2 was an order of magnitude
      higher than in the intact MDCK cell line. The water permeability of the nuclear
      membrane in both cell lines was found to be unlimited. Thus the intranuclear
      fluid belongs to the osmotically active portion of the cell. We conclude that the
      use of confocal microscopy provides a sensitive and reproducible method for
      measurement of water permeability in different types of adherent cells and
      potentially for coverslip-attached tissue preparations.

PMID- 10968209
TI  - Interaction of phloretin with membranes: on the mode of action of phloretin at
      the water-lipid interface.
AB  - The interaction of phloretin with single lipid bilayers on a spherical support
      and with multilamellar vesicles was studied by differential scanning calorimetry
      (DSC) and nuclear magnetic resonance (NMR). The results indicated that phloretin
      interacts with the lipid layer and changes its structural parameters. In DSC
      experiments, phloretin in its neutral form strongly decreased the lipid phase
      transition temperature and slightly reduced the cooperativity of the phase
      transition within the lipid layer. In NMR measurements, phloretin led to an
      increase of the transverse relaxation time constant but had no effect on the spin
      lattice relaxation time constant. The overall dipole moment of phloretin was
      experimentally determined and was found to be roughly 40% lower than has been
      published previously. This result suggested that the size of the dipole moment of
      phloretin does not provide such a high contribution to the effect of phloretin on
      the dipole potential of monolayers and bilayers as has been published previously.
      To understand the discrepancy between phloretin adsorption and dipole potential
      change, we performed computational conformational analysis of phloretin in the
      gas phase. The results showed that a wide distribution of the dipole moments of
      phloretin conformers exists, which mainly depends on the orientation of the OH
      moieties. The adsorption of phloretin as determined from its binding to solid
      supported bilayers differed from the one determined from dipole potential
      measurements on black lipid membranes. The difference between the phloretin
      dissociation constants of both types of experiments suggested a change of its
      dipole moment normal to the membrane surface in a concentration-dependent manner,
      which was in agreement with the results of the computational conformational
      analysis.

PMID- 10968210
TI  - Formation of unilamellar vesicles by repetitive freeze-thaw cycles:
      characterization by electron microscopy and 31P-nuclear magnetic resonance.
AB  - It has been reported that repetitive freeze-thaw cycles of aqueous suspensions of
      dioleoylphosphatidylcholine form vesicles with a diameter smaller than 200 nm. We
      have applied the same treatment to a series of phospholipid suspensions with
      particular emphasis on dioleoylphosphatidylcholine/dioleoylphosphatidic acid
      (DOPC/DOPA) mixtures. Freeze-fracture electron microscopy revealed that these
      unsaturated lipids form unilamellar vesicles after 10 cycles of freeze-thawing.
      Both electron microscopy and broad-band 31P NMR spectra indicated a disparity of
      the vesicle sizes with a highest frequency for small unilamellar vesicles
      (diameters < or =30 nm) and a population of larger vesicles with a frequency
      decreasing exponentially as the diameter increases. From 31P NMR investigations
      we inferred that the average diameter of DOPC/DOPA vesicles calculated on the
      basis of an exponential size distribution was of the order of 100 nm after 10
      freeze-thaw cycles and only 60 nm after 50 cycles. Fragmentation by repeated
      freeze-thawing does not have the same efficiency for all lipid mixtures. As found
      already by others, fragmentation into small vesicles requires the presence of
      salt and does not take place in pure water. Repetitive freeze-thawing is also
      efficient to fragment large unilamellar vesicles obtained by filtration. If
      applied to sonicated DOPC vesicles, freeze-thawing treatment causes fusion of
      sonicated unilamellar vesicles into larger vesicles only in pure water. These
      experiments show the usefulness of NMR as a complementary technique to electron
      microscopy for size determination of lipid vesicles. The applicability of the
      freeze-thaw technique to different lipid mixtures confirms that this procedure is
      a simple way to obtain unilamellar vesicles.

PMID- 10968211
TI  - Formation of model lipid bilayers at the silica-water interface by co-adsorption
      with non-ionic dodecyl maltoside surfactant.
AB  - This present article describes a new and simple method for preparing model lipid
      bilayers. Stable and reproducible surface layers were produced at silica surfaces
      by co- adsorbing lipid with surfactant at the silica surface from mixed micellar
      solutions. The adsorption was followed in situ by use of ellipsometry. The mixed
      micellar solution consisted of a lipid (L-alpha-dioleoyllecithin) and a non-ionic
      sugar-based surfactant (n-dodecyl-beta-maltoside). The latter showed, by itself,
      no affinity for the surface and could, therefore, easily be rinsed off the
      surface after the adsorption step. By first adsorbing from solutions with high
      lipid and surfactant concentrations and then, in succession, rinsing and re
      adsorbing from solutions with lower lipid-surfactant concentrations, a dense
      packed lipid bilayer was produced at the silica surface. The same result can be
      achieved in a one-step process where the rinsing, after adsorption from the
      concentrated solution, is performed very slowly. The thickness of the adsorbed
      lecithin bilayer after this treatment found was to be about 44 +/- 3 A, having a
      mean refractive index of 1.480 +/- 0.004. The calculated surface excess of lipids
      on silica was about 4.2 mg m(-2), giving an average area per lipid molecule in
      the two layers of 62 +/- 3 A2. The physical characteristic of the adsorbed
      bilayer is in good agreement with previously reported data on bulk and surface
      supported lipid bilayers. However, in contrast to previous investigations, we
      found no support for the presence of a thicker multi-molecular water layer
      located between the lipid layer and the solid substrate.

PMID- 10968212
TI  - Microstructure and dynamic surface properties of surfactant protein SP
      B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein
      bilayers.
AB  - Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or
      20% (w/w) surfactant protein SP-B have been reconstituted and spread at air
      liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from
      these preparations were qualitatively comparable to the isotherms of the
      corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out at
      higher pressures from vesicle-spread films than from solvent-spread monolayers.
      SP-B caused a marked decrease on the rate of relaxation of DPPC collapse phases
      to equilibrium pressures in all the lipid/protein films assayed. This stabilizing
      effect was higher in vesicle-spread than in solvent-spread monolayers. Inclusion
      in the films of traces of the fluorescent probe NBD-PC (1 mol%) and use of a
      fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red,
      allowed for direct observation of protein and lipid domains at the interface by
      epifluorescence microscopy. Upon compression, SP-B altered the packing of
      phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction
      of the area of liquid-condensed domains, in a way similar to its effect in
      solvent-spread monolayers. SP-B was not associated with condensed regions of the
      films. Fluorescence images from vesicle-spread films showed discrete fluorescent
      aggregates that could be consistent with the existence of lipid-protein vesicles
      in close association with the monolayer. Both the retention of SP-B at higher
      surface pressures and the greater stability of collapse phases of DPPC/SP-B films
      prepared by spreading from liposomes in comparison to those spread from solvents
      can be interpreted as a consequence of formation of complex bilayer-monolayer
      interacting systems.

PMID- 10968213
TI  - A two-dimensional many-body system with competing interactions as a model for
      segregation of photosystems in thylakoids of green plants.
AB  - We address the segregation of photosystems I (PSI) and II (PSII) in thylakoid
      membranes by means of a molecular dynamics method. We assume a two-dimensional
      (in-plane) problem with PSI and PSII being represented by particles with
      different values of negative charge. The pair interactions between particles
      include a screened Coulomb repulsive part and am exponentially decaying
      attractive part. Our modeling results suggest that the system may have a
      complicated phase behavior, including a quasi-crystalline phase at low ionic
      screening, a disordered phase and, in addition, a possible "clotting" agglomerate
      phase at high screening where the photosystems tend to clot together. The
      relevance of the observed phenomena to the stacking of thylakoid membranes is
      discussed.

PMID- 10968214
TI  - Mean residence time of molecules diffusing in a cell bounded by a semi-permeable
      membrane: Monte Carlo simulations and an expression relating membrane transition
      probability to permeability.
AB  - The rapid exchange of water across erythrocyte membranes is readily measured
      using an NMR method that entails doping a suspension of cells with a moderately
      high concentration of Mn(2-) and measuring the rate of transverse relaxation of
      the nuclear magnetisation. Analysis of the data yields an estimate of the rate
      constant for membrane transport, from which the membrane permeability can be
      determined. It is assumed in the analysis that the efflux rate of the water is
      solely a function of the rate of membrane permeation and that the time it takes
      for intracellular water molecules to diffuse to the membrane is relatively
      insignificant. The limits of this assumption were explored by using random-walk
      simulations of diffusion in cells modelled as parallel planes, spheres, and
      biconcave discs. The rate of membrane transport was specified in terms of a
      transition probability but it was not initially clear what the relationship
      should be between this parameter and the diffusional membrane permeability P(d).
      This relationship was derived and used to show that the mean residence time for a
      water molecule is determined by P(d) when the diffusion coefficient is above a
      certain threshold value; it is determined by the distance to the membrane below
      that value.

PMID- 10968215
TI  - A comparison of head-unrestrained and head-restrained pursuit: influence of eye
      position and target velocity on latency.
AB  - Horizontal step-ramp target trajectories were used to study the initiation of
      head-unrestrained and head-restrained pursuit in the monkey. In a first series of
      experiments, initial target position (0 degrees, 5 degrees, or 30 degrees,
      contraversive to the direction of pursuit), fixation duration, target velocity
      (20 degrees, 40 degrees, 60 degrees and 80 degrees/s), and target direction were
      randomized in order to minimize predictive responses. Animals pursued the target
      either with their eyes alone (head-restrained: HR condition) or with a
      combination of eye and head movements (head-unrestrained: HU condition). Head
      motion onset consistently lagged pursuit onset (i.e., eye motion) by 50 ms or
      more in the HU condition, and was influenced by target velocity as well as by
      initial target position. Pursuit onset latencies did not vary systematically as a
      function of target velocity in either the HR or HU conditions. However, pursuit
      initiation latencies tended to be longer in the HU condition as compared to the
      HR condition when target motion started from the most contraversive position. A
      second series of experiments revealed that this difference in HR and HU pursuit
      onset latencies could be explained by the effects of initial eye-in-head
      position; more contraversive initial eye positions yielded shorter pursuit
      latencies in both conditions, and the monkeys generally moved their head towards
      the target in the HU condition, resulting in smaller eye-in-head eccentricities.
      Furthermore, we found that initial gaze and head positions had little or no
      effect on pursuit latencies. We conclude that the latency for pursuit initiation
      is similar irrespective of whether an animal is head-restrained or head
      unrestrained, when initial eye position is held constant.

PMID- 10968216
TI  - The neural basis of egocentric and allocentric coding of space in humans: a
      functional magnetic resonance study.
AB  - The spatial location of an object can be represented in the brain with respect to
      different classes of reference frames, either relative to or independent of the
      subject's position. We used functional magnetic resonance imaging to identify
      regions of the healthy human brain subserving mainly egocentric or allocentric
      (object-based) coordinates by asking subjects to judge the location of a visual
      stimulus with respect to either their body or an object. A color-judgement task,
      matched for stimuli, difficulty, motor and oculomotor responses, was used as a
      control. We identified a bilateral, though mainly right-hemisphere based, fronto
      parietal network involved in egocentric processing. A subset of these regions,
      including a much less extensive unilateral, right fronto-parietal network, was
      found to be active during object-based processing. The right-hemisphere
      lateralization and the partial superposition of the egocentric and the object
      based networks is discussed in the light of neuropsychological findings in brain
      damaged patients with unilateral spatial neglect and of neurophysiological
      studies in the monkey.

PMID- 10968217
TI  - Neural compensation for mechanical differences between hand and foot during
      coupled oscillations of the two segments.
AB  - (1) Rhythmic flexion-extensions of the hand and foot on one side were performed
      by ten male and nine female subjects. Limbs were rotated in the same direction
      (in-phase) or in opposite directions (anti-phase). Oscillation frequency ranged
      from 0.6 to 3.2 Hz for in-phase and to 2.2 Hz for anti-phase movements. In both
      genders, movement synchrony was more strictly maintained during anti-phase than
      during in-phase coupling. (2) EMG recordings showed that, in males, movement
      synchrony was achieved by activating hand movers in advance of foot movers. This
      phase advance increased as the oscillation frequency increased. In females,
      instead, muscles of the two limbs were activated almost simultaneously over most
      of the frequency range. Since the different timing of muscle activation in the
      two genders suggests that their limbs have different mechanical characteristics,
      the frequency response of each limb was estimated in either gender. The frequency
      response between 0.6 and 3.2 Hz was evaluated in five males and five females by
      measuring the phase delay between the onset of the EMG activity and the onset of
      the related movement, both when the limbs were moved in isolation and when they
      were coupled. (3) In uncoupled conditions, the hand and foot curves were roughly
      parallel in females, the phase delay being about 45 degrees larger in the hand
      than in the foot. In males, the curves were also separated by 45 degrees at the
      lowest frequencies but they further diverged when the frequency was raised,
      because of a faster increase in the phase delay in the hand than in the foot.
      These results indicate that, when the extremities have to be coupled, a nervous
      compensation is necessary and that it must be different in the two genders. (4)
      Analysis of the phase-response when limbs were coupled showed that synchrony was
      approached by two mechanisms: (a) an earlier EMG activation of the hand movers,
      preferentially utilised by males during in-phase coupling; and (b) a change in
      the viscoelastic properties of one extremity, which reduces (or eliminates) the
      difference between their frequency responses as well as between the EMG onsets of
      hand and foot movers. This second mechanism was utilised by both genders during
      anti-phase coupling.

PMID- 10968218
TI  - Antiparkinsonian and neuroprotective effects of modafinil in the mptp-treated
      common marmoset.
AB  - The psychostimulant drug, modafinil, protects rodents against 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) toxicity, striatal ischemia and partial
      transection of the nigro-striatal pathway. We now report on the ability of
      modafinil to reverse motor disability in MPTP-treated common marmosets and to
      prevent MPTP-induced nigral cell death in this species. In the initial
      experiments, adult common marmosets were treated with MPTP to produce stable
      motor deficits. The subsequent administration of modafinil (10, 30 or 100
      mg/kg/day, p.o.) produced a dose-dependent reversal of motor disability. In a
      subsequent experiment, normal common marmosets were concurrently treated with 10,
      30 or 100 mg/kg of modafinil once daily by gavage during acute MPTP
      administration (daily for 5 days), continuing for 2 weeks after the last dose of
      MPTP. Modafinil dose-dependently prevented the decline in motor activity normally
      produced by MPTP treatment. MPTP treatment caused a 76% loss of nigral tyrosine
      hydroxylase-immunoreactive cells in placebo-treated animals, and this was dose
      dependently prevented by modafinil. At the highest dose (100 mg/kg/day) of
      modafinil, there was no significant loss of tyrosine-hydroxylase-immunoreactive
      cells in the substantia nigra compared with normal animals. MPTP treatment also
      reduced striatal dopamine uptake sites by 95%, as measured by specific [3H]
      mazindol binding, compared with normal controls. Modafinil treatment dose
      dependently reduced the loss of specific [3H]-mazindol binding. Behavioural and
      morphological evidence in the present study indicate a potential antiparkinsonian
      and neuroprotective role for modafinil, which may form a new pharmacological
      approach to the treatment of Parkinson's disease.

PMID- 10968219
TI  - Experimental tests of a neural-network model for ocular oscillations caused by
      disease of central myelin.
AB  - Spontaneous sinusoidal oscillations of the eyes are a feature of disorders
      affecting central myelin, including multiple sclerosis. The mechanism responsible
      for these oscillations (pendular nystagmus) is unknown. We tested the hypothesis
      that pendular nystagmus is due to instability of the neural integrator, a network
      of neurons that normally guarantees steady gaze by mathematically integrating
      premotor signals. It was possible to make a model of the neural integrator
      unstable, and abnormal feedback then produced sustained oscillations so that it
      simulated pendular nystagmus. One prediction of the model is that a large
      premotor signal, such as is required to generate a rapid (saccadic) eye movement,
      will transiently suppress the activity of some neurons in the network, and that
      this will "reset" the oscillations, i.e., produce a phase shift; larger saccades
      will produce greater phase shifts. Alternatively, if the source of pendular
      nystagmus is outside the neural integrator (i.e., is present on velocity inputs
      to the stable integrator), then it may not be possible to reset the oscillations
      with a saccadic eye movement. We compared the phase relationships of pendular
      nystagmus prior to and following saccades in six patients with multiple sclerosis
      (MS). All patients showed phase shifts (median 64 degrees) of their ocular
      oscillations following large (more than 10 degrees) saccades; smaller saccades
      (less than 5 degrees) caused smaller phase shifts (median 17 degrees). Our
      findings suggest that, in MS, pendular nystagmus arises from an instability in
      the feedback control of the neural integrator for eye movements, which depends on
      a distributed network of neurons in the brainstem and cerebellum.

PMID- 10968220
TI  - Influence of conflicting visual, inertial and substratal cues on head direction
      cell activity.
AB  - In order to navigate efficiently, animals can benefit from internal
      representations of their moment-to-moment orientation. Head-direction (HD) cells
      are neurons that discharge maximally when the head of a rat is oriented in a
      specific ("preferred") direction in the horizontal plane, independently from
      position or ongoing behavior. This directional selectivity depends on
      environmental and inertial cues. However, the mechanisms by which these cues are
      integrated remain unknown. This study examines the relative influence of visual,
      inertial and substratal cues on the preferred directions of HD cells when cue
      conflicts are produced in the presence of the rats. Twenty-nine anterior dorsal
      thalamic (ATN) and 19 postsubicular (PoS) HD cells were recorded from 7 rats
      performing a foraging task in a cylinder (76 cm in diameter, 60 cm high) with a
      white card attached to its inner wall. Changes in preferred directions were
      measured after the wall or the floor of the cylinder was rotated separately or
      together in the same direction by 45 degrees, 90 degrees or 180 degrees, either
      clockwise or counterclockwise. Linear regression analyses showed that the
      preferred directions of the HD cells in both structures shifted by approximately
      =90% of the angle of rotation of the wall, whether rotated alone or together with
      the floor (r2>0.87, P<0.001). Rotations of the floor alone did not trigger
      significant shifts in preferred directions. These results indicate that visual
      cues exerted a strong but incomplete control over the preferred directions of the
      neurons, while inertial cues had a small but significant influence, and
      substratal cues were of no consequence.

PMID- 10968221
TI  - Response characteristics of neurons in the pulvinar of awake cats to saccades and
      to visual stimulation.
AB  - We studied responses of pulvinar neurons in awake cats that were allowed to
      execute spontaneous eye movements. Extracellular cell activity during saccades,
      saccade-like image shifts, and various stationary visual stimuli was recorded
      together with the animals' eye positions. All neurons analyzed had receptive
      fields that covered most of the central 80x80 degrees of the animals' visual
      field and did only respond to large (>20 degrees) visual stimuli. According to
      their response properties, recorded neurons were divided into three populations.
      The first group, termed "S neurons" (16%), responded when the animals performed
      saccades but were unresponsive to any of the visual stimuli tested. These neurons
      do not seem to receive a visual input that is strong enough to drive them. The
      second group, termed "V neurons" (51%), responded to various visual stimuli
      including saccade-like image motion when the eyes were stationary, but not when
      the animals executed saccades. V neurons therefore distinguish retinal image
      movements that are generated externally from internally generated image motion.
      Finally, "SV neurons" (31%) responded when the animals made saccades as well as
      to saccade-like image motion or to stationary stimuli. Although these neurons do
      not distinguish self-induced retinal image motion from motion generated by
      external stimulus movements, they must receive non-retinal motion-related input,
      because responses elicited by saccades had shorter latencies than responses to
      saccade-like stimulus movements. Only SV neurons resemble response properties of
      pretectal neurons that project to the pulvinar and that comprise the major
      subcortical visual input. The functional significance of pulvinar neuronal
      populations for visual and visuomotor information processing is discussed.

PMID- 10968222
TI  - Connections of Purkinje cell axons of lobule X with vestibulocerebellar neurons
      projecting to lobule X or IX in the rat.
AB  - Connections of Purkinje cell axons of lobule X (nodulus) with vestibulocerebellar
      neurons projecting to lobule X or IX (uvula) were revealed in the rat. Purkinje
      cell axons were anterogradely labeled with biotinylated dextran (BD) injected
      into sublobule Xa while vestibular neurons were retrogradely labeled with cholera
      toxin subunit B (CTB) injected into sublobule Xa or IXc. Labeled terminals of
      Purkinje cell axons of lobule X were numerous in the superior vestibular nucleus
      (SV), medial parts of the parvocellular (MVpc) and the caudal part (MVc) of the
      medial vestibular nucleus (MV), and group y. These subdivisions of the vestibular
      nuclei contained many neurons projecting to lobule X or IX. Lobule-X-projecting
      and lobule-IX-projecting neurons were in contact with terminals of Purkinje cell
      axons of lobule X in the MVpc and MVc. They were distributed dorsally to medially
      in medial parts of the MVpc and MVc. The present study suggests that Purkinje
      cells in lobule X regulate the output of a population of lobule-X-projecting or
      lobule-IX-projecting neurons of the MVpc and MVc.

PMID- 10968223
TI  - Reorientation of a visually evoked postural response during passive whole body
      rotation.
AB  - Visually evoked postural responses (VEPR) to a roll-motion rotating disk were
      recorded from normal subjects standing on a yaw axis motorised rotating platform.
      The disk was fluorescent so that subjects could be tested in an otherwise dark
      room. Movements of the head and centre of foot pressure were measured while
      subjects looked at the disk with their eyes and head in the primary position and
      while the rotating platform moved the subjects randomly to 0, +/-45 degrees and
      +/-90 degrees angles from the visual stimulus. Subjects were instructed to
      maintain fixation on the centre of the rotating disk but the amount of horizontal
      eye and head movement used was not specified. Platform rotational velocity was
      set near threshold values for perception of self-rotation (approximately 2
      degrees/s) so that subjects would find it difficult to reconstruct the angle
      travelled. The data showed that the VEPR occurred in the plane of disk rotation,
      regardless of body position with respect to the disk, and despite the subjective
      spatial disorientation induced by the experiment. Averages of the response
      revealed a good match (gain=0.95) between disk orientation and sway direction.
      The horizontal gaze deviation required to fixate the centre of the disk was
      largely achieved by head motion (head 95%, eye 5%). The results confirm previous
      results that VEPRs are reoriented according to horizontal gaze angle. In
      addition, we show that the postural reorientation is independent of cognitively
      or visually mediated knowledge of the geometry of the experimental conditions. In
      the current experiments, the main source of gaze position input required for VEPR
      reorientation was likely to be provided by neck afferents. The results support
      the notion that vision controls posture effectively at any gaze angle and that
      this is achieved by combining visual input with proprioceptively mediated gaze
      angle signals.

PMID- 10968224
TI  - Low frequency depression of H-reflexes in humans with acute and chronic spinal
      cord injury.
AB  - We measured low-frequency depression of soleus H-reflexes in individuals with
      acute (n=5) and chronic (n=7) spinal-cord injury and in able-bodied controls
      (n=7). In one acute subject, we monitored longitudinal changes in low-frequency
      depression of H-reflexes over 44 weeks and examined the relationship between H
      reflex depression and soleus-muscle fatigue properties. Soleus H-reflexes were
      elicited at 0.1, 0.2, 1, 5, and 10 Hz. The mean peak-to-peak amplitude of ten
      reflexes at each frequency was calculated, and values obtained at each frequency
      were normalized to 0.1 Hz. H-reflex amplitude decreased with increasing
      stimulation frequency in all three groups, but H-reflex suppression was
      significantly larger in the able-bodied and acute groups than in the chronic
      group. The acute subject who was monitored longitudinally displayed reduced low
      frequency depression with increasing time post injury. At 44 weeks post injury,
      the acute subject's H-reflex depression was similar to that of chronic subjects,
      and his soleus fatigue index (assessed with a modified Burke fatigue protocol)
      dropped substantially, consistent with transformation to faster muscle. There was
      a significant inverse correlation over the 44 weeks between the fatigue index and
      the mean normalized H-reflex amplitude at 1, 5, and 10 Hz. We conclude that: (1)
      the chronically paralyzed soleus muscle displays impaired low-frequency
      depression of H-reflexes, (2) attenuation of rate-sensitive depression in humans
      with spinal-cord injury occurs gradually, and (3) changes in H-reflex
      excitability are generally correlated with adaptation of the neuromuscular
      system. Possible mechanisms underlying changes in low-frequency depression and
      their association with neuromuscular adaptation are discussed.

PMID- 10968225
TI  - Hitting moving objects. The dependency of hand velocity on the speed of the
      target.
AB  - In previous studies, subjects did not hit slowly moving objects as quickly as
      fast ones, despite being instructed to hit them all as quickly as possible. In
      those studies the targets moved at constant but unpredictable velocities, and it
      has been suggested that subjects were unable to adjust the hand's path to suit
      the velocity of the target. To compensate for this, they adjusted the speed of
      their hand to that of the target (speed coupling). According to this hypothesis,
      speed coupling is necessary only when subjects are unable to correctly predict
      the next target velocity and only if they have to be accurate. We show here that
      decreasing the uncertainty about the upcoming target's velocity or enlarging the
      tip of the hitting weapon does not make speed coupling disappear. Moreover, there
      is a negative correlation between hand velocity and strength of speed coupling,
      whereas the hypothesis predicts a positive correlation. The hypothesis is
      therefore rejected. We propose that speed coupling is a result of different speed
      accuracy tradeoffs applying to different target velocities.

PMID- 10968226
TI  - Reduced interhemispheric inhibition in musicians.
AB  - In vivo magnetic resonance imaging has revealed that the anterior half of the
      corpus callosum is larger in musicians trained intensively from an early age than
      in untrained subjects. The corpus callosum is crucial for the coordination of
      bimanual motor activity, but neurophysiological correlates of morphological
      differences in the corpus callosum of musicians are not known. In the present
      study we have used transcranial magnetic stimulation (TMS) to assess
      interhemispheric inhibition in six adult professional musicians who began musical
      training at an early age. Conditioning TMS was applied to the hand area of the
      motor cortex of one hemisphere, followed 4-16 ms later by a test stimulus applied
      to the other hemisphere. Tests were performed at rest, and with the first dorsal
      interosseous muscle contralateral to the conditioning hemisphere voluntarily
      active. Conditioning TMS in musicians was 29% less effective at reducing the size
      of the test MEP at rest, and 63% less effective in the active condition, compared
      with control subjects. We conclude that transcallosal interhemispheric inhibitory
      circuits activated by TMS are less effective in musicians than in controls.

PMID- 10968227
TI  - Response properties of neurons in the central nucleus and external and dorsal
      cortices of the inferior colliculus in guinea pig.
AB  - The inferior colliculus (IC) represents a mid-brain structure which integrates
      information from many ascending auditory pathways, descending corticotectal
      projections and intercollicular pathways. The processing of information is
      different in each of the three main subdivisions of the IC--the central nucleus
      (CNIC), the dorsal cortex (DCIC) and the external cortex (ECIC)--which may be
      distinguished morphologically as well as by different inputs and outputs. To
      assess the differences in information processing we compared the response
      properties of single neurons in individual subnuclei of the IC in anesthetized
      guinea pigs. In comparison with DCIC and ECIC neurons, the CNIC neurons as a
      group were characterized by a sharper frequency tuning (as expressed by Q10
      values), a lower average threshold, a shorter average first-spike latency of
      response to tones at the characteristic frequency (CF), a higher occurrence of
      non-monotonic rate/level functions and a higher rate of spontaneous activity.
      CNIC neurons and DCIC neurons reacted to tones at the CF more frequently by a
      sustained type of response than did ECIC neurons. The difference between the
      parameters of DCIC neuronal activity and ECIC neuronal activity was found to be
      smaller. The frequency tuning (expressed in Q10 values), spontaneous activity and
      dominance of monotonic rate/level functions were very similar in both structures;
      ECIC neurons expressed a higher average threshold and a shorter average first
      spike latency than did DCIC neurons. Responsiveness expressed as the average
      maximal firing rate to tones at the CF was significantly higher in the CNIC than
      in the ECIC. The results give additional support to the idea that the CNIC is a
      part of a fast, frequency-tuned, low threshold and intensity-sensitive ascending
      pathway, whereas the other two subdivisions are involved in additional processing
      of information that involves feedback loops and polysensory pathways.

PMID- 10968228
TI  - Absence of nerve specificity in human cutaneous reflexes during standing.
AB  - Cutaneous reflexes in lower limb muscles were recorded from healthy human
      subjects after non-noxious electrical stimulation of superficial peroneal (SP),
      sural and distal tibial nerves while subjects: (1) made graded voluntary
      contractions of the ankle and knee extensor and flexor muscles while mimicking
      late stance or heel strike limb positions; and (2) walked on a treadmill at
      speeds of 2 and 4 km/h. During standing, net reflexes were predominantly
      suppressive and graded with background EMG. In contrast, during walking net
      reflexes were mostly facilitatory and uncorrelated with background EMG. Opposite
      signs (negative during standing, positive during walking) and significant
      differences of the reflex ratio (net reflex/background EMG) were seen in most leg
      muscles. The nerve stimulated did not determine the sign of the net reflex while
      standing: nerve specificity was absent. We suggest that during standing, where
      maintenance of posture is of primary importance, there is a reduction of effort
      that led to increased cutaneous input (i.e., a global suppressive response),
      while during walking there is a modulation of reflexes which is independent of
      muscle activation level but closely tied to events occurring in the step cycle.

PMID- 10968229
TI  - Motor imagery and visual event recognition.
AB  - In order to investigate the influence of covert motor processes in the
      recognition of visual events, we compared the response times (RT) in two similar
      tasks, one involving a to-be-grasped object and the other involving a to-be
      observed object. In one task, we asked right-handed subjects to tell whether an
      observed screwdriver presented in different orientations and rotating on its main
      axis was screwing or unscrewing (screwdriver task). In the other task the visual
      stimuli were precisely the same, but subjects had to think of the screwdriver as
      being the pivot pin of an imagined clock, turning its hands from the back (clock
      task). They had to tell whether the imagined clock hands were moving clockwise or
      counterclockwise. In the screwdriver task, a prominent right-left asymmetry
      consisting of higher RTs for stimulus orientations awkward for a right-hand grip
      was present, suggesting that subjects adopted a strategy based upon mentally
      simulating the grabbing of the screwdriver handle with the dominant hand.
      Consistent with the hypothesis that the crucial factor that triggers these motor
      imagery processes is the "graspability" of the relevant object in the scene, in
      the clock task the right-left asymmetry disappeared in most subjects, RTs
      mirroring the symmetry of the visual stimuli. These findings indicate that, when
      interpreting a scene involving a to-be-grasped object, a strategy based upon
      motor imagery (mental grasping), probably unfolding procedural knowledge, is
      activated. When the scene involves a to-be-observed object, the recognition task
      can be accomplished through other, possibly visual, strategies.

PMID- 10968230
TI  - Cortical malformations: a frequent cause of epilepsy in children.
AB  - In this review, a simplified scheme for classification of cortical malformations
      is introduced and illustrated based on the work of Barkovich et al. [8]. Detailed
      MRI studies identify cortical malformations as a major cause of epilepsy in
      children. Two aspects that are becoming increasingly important for the
      paediatrician are emphasised. First, knowledge of the genetic background of
      cortical malformations is necessary for appropriate genetic counselling. Although
      the majority of cortical malformations occur sporadically, recent studies have
      shown a familial pattern in specific epilepsy syndromes associated with cortical
      malformations. Second, the epilepsy becomes refractory to the common anti
      epileptic drugs in many patients with cortical malformations so that epilepsy
      surgery should be considered. In this respect, the paediatrician can play a
      pivotal role in referring candidate patients for further specialised assessment.
      CONCLUSION: The input of the paediatrician will become crucial to link clinical,
      genetic and neuro-imaging data in children with the great variety of possible
      cortical malformations.

PMID- 10968231
TI  - Detection and follow up of exocrine pancreatic insufficiency in cystic fibrosis:
      a review.
AB  - Pancreatic function testing is particularly difficult when the degree of
      remaining function has to be quantified. Detection of pancreatic insufficiency
      can suggest the diagnosis of cystic fibrosis (CF). It is, however, also important
      to follow the degree of pancreatic insufficiency in CF since its function can
      decline with age. Adaptation of pancreatic enzyme replacement therapy on residual
      function is necessary. Different tests with their advantages and disadvantages
      are critically reviewed in this article with respect to specificity, sensitivity,
      performance and cost-effectiveness. CONCLUSION: Elastase-1 detection in faeces is
      probably the easiest test for the detection of pancreatic insufficiency in cystic
      fibrosis. For clinical follow-up tests, measuring the fat assimilation such as
      steatocrit and breath tests are more suited.

PMID- 10968232
TI  - Vestibular anomalies in CHARGE syndrome: investigations on and consequences for
      postural development.
AB  - Recently, vestibular anomalies have been described as a frequent feature in
      children with coloboma-heart-atresia-retarded-genital-ear (CHARGE) syndrome. They
      are likely to play an important role in the psychomotor retardation affecting
      these children. In order to test this hypothesis, we prospectively performed
      complete vestibular investigations in a series of 17 CHARGE syndrome patients
      including inner ear CT scan and functional vestibular evaluation of both canal
      and otolith functions. These results were correlated with the postural anomalies
      observed during the children's development and showed that vestibular dysfunction
      is a constant feature in CHARGE syndrome and has very good sensitivity for
      confirming the diagnosis. Anomalies of semicircular canals were frequently found
      (94%), easily detectable on CT scan and associated with no response on canal
      function evaluation. They were considered as partly responsible for the
      retardation of postural stages. Vestibular functional tests were consistently
      abnormal but allowed detection of residual otolith function in most patients
      (94%). All children of this series had an atypical pattern of postural behaviour
      that we consider to be related to their vestibular anomalies. Residual otolith
      function seems to have a positive influence for postural development. CONCLUSION:
      Vestibular investigations are valuable for diagnosis, developmental assessment,
      and adaptation of specific rehabilitation programmes in CHARGE syndrome patients.

PMID- 10968233
TI  - Longitudinal growth in HIV-negative boys with haemophilia.
AB  - It has been shown that HIV-positive haemophilic children develop growth
      retardation. As not only the HIV infection but also other disease-related factors
      might compromise growth in these children, growth data were analysed in a
      longitudinal cross-sectional manner in 84 HIV-negative haemophilic patients from
      two university clinics. A total of 2-24 height and weight measurements (median 6)
      were recorded in each patient resulting in 683 single values collected between
      1977-1995. Height SDS of all haemophilic boys was -0.31 +/- 2.13 (mean +/- SD, NS
      versus 0) and body mass index SDS was 0.21 +/- 3.49 (mean SD, NS versus 0) at
      first measurement and remained unchanged throughout the observation period.
      Neither height nor body mass index differed with respect to the severity of
      haemophilia (mild/moderate/severe) or the study centre (Vienna/Prague).
      CONCLUSION: Growth in HIV-negative patients with haemophilia is not affected in
      spite of the immunological abnormalities attributed to the substitution therapy
      or the bleeding episodes in the joints with the potential effect on the growth
      plate.

PMID- 10968234
TI  - Osteopetrorickets: case report.
AB  - We report the case of a baby girl who presented with rickets at 3 months. At the
      age of 5 months she was readmitted because of nystagmus and a diagnosis of
      osteopetrosis was made on the basis of clinical and radiological findings.
      Rickets is a paradoxical feature of osteopetrosis resulting from inability to
      maintain a normal calcium-phosphorus balance. In our patient the onset of rickets
      before other symptoms of osteopetrosis suggests a primary defect. CONCLUSION: It
      is possible that patients with osteopetrosis and rickets (osteopetrorickets)
      represent a different mutation like the osteopetrosis mouse, which is the only
      animal mutation with rickets.

PMID- 10968235
TI  - Cutaneous malignant melanoma in children.
AB  - Although rare, malignant melanoma does occur in children. As in adults, prognosis
      clearly depends on rapid diagnosis and early treatment. This paper describes
      eight cases of confirmed malignant melanoma in children, with full case history
      and pathological findings. Mean follow-up was 109.8 months. Early diagnosis and
      low Breslow indices provide good results in the form of absence of recurrence and
      long-term survival prognosis. The paper also includes a discussion of specific
      risk factors affecting children. In order to encourage earlier diagnosis and
      improved prognosis, it must be kept in mind that in children too, the skin as an
      organ should be included in any physical examination. CONCLUSION: As for adult
      patients, early clinical detection, speedy histological confirmation and prompt
      surgery is the only way to achieve a long survival period for children suffering
      from malignant melanoma.

PMID- 10968236
TI  - Serum transferrin receptor in children and adolescents with inflammatory bowel
      disease.
AB  - Iron studies are difficult to interpret in patients with chronic inflammatory
      states such as inflammatory bowel disease (IBD). Serum transferrin receptor (TfR)
      has been reported to be a reliable tool for the diagnosis of iron deficiency in
      adults. Our aim was to evaluate the role of serum TfR in diagnosing iron
      deficiency in children and adolescents with IBD. A total of 63 consecutive
      patients with IBD, aged 9 to 22 years (median 15 years), were tested for serum
      haemoglobin level, mean corpuscular volume (MCV), and serum iron, transferrin,
      ferritin and serum TfR levels. Those found to be anaemic were compared with seven
      age-matched subjects with iron deficiency anaemia (IDA) and 24 age-matched
      children without signs of anaemia or inflammation. Of the 63 patients with IBD,
      26 had anaemia. Based on ferritin levels and MCV indices, anaemia was classified
      as IDA in 11 patients and as anaemia of chronic disease (ACD) in 15 patients.
      Mean serum TfR level in normal controls was 3.5 mg/l (range 1.2-8.2 mg/l). Mean
      (+/-SD) serum TfR levels were significantly lower in the IBD patients with ACD
      (5.3 +/- 2.3 mg/l) than in the IBD patients with IDA (8.2 +/- 3.1 mg/l) (P <
      0.05). Serum TfR levels above 5 mg/l identified 10/11 IBD patients with IDA. The
      calculated TfR/ferritin ratio was 84 (range 17-367) for controls and 133 (range
      6.4-1840) for IBD patients. A cut-off level of 350 (91% sensitivity, 100%
      specificity, 100% positive predictive value, 98% negative predictive value) was
      established for the diagnosis of IDA in IBD. CONCLUSION: The results suggest that
      serum transferrin receptor is a useful parameter for the diagnosis of iron
      deficiency in inflammatory bowel disease, in particular, the transferrin
      receptor/ferritin ratio with a cut-off level > or = 350.

PMID- 10968237
TI  - Preliminary experience with the angiotensin II receptor antagonist irbesartan in
      chronic kidney disease.
AB  - Blocking the formation of angiotensin II with converting enzyme inhibitors is an
      established intervention for kidney disease. The advent of antagonists of the
      angiotensin II receptor has increased the options for inhibiting the renin
      angiotensin-aldosterone system. In adults, angiotensin II antagonists have
      antihypertensive and antiproteinuric effects similar to those of converting
      enzyme inhibitors and an adverse effect profile similar to that of placebo. In
      children, no information is available on angiotensin II antagonists. A total of
      20 children (aged 4 to 17 years) with chronic kidney disease received the
      angiotensin II antagonist irbesartan given once daily. They had hypertension (n =
      11), overt proteinuria (n = 3), or both (n = 6). At last follow-up, 2 to 17
      months after starting irbesartan (median dosage: 3.3 mg/kg body weight daily),
      arterial pressure was significantly reduced: the systolic value by 16 [6-22] and
      the diastolic value by 11 [4-22] mmHg (median and interquartile range). In nine
      patients with proteinuria, the urinary albumin/creatinine ratio significantly
      decreased by 145 [105-209] mg/mmol. The frequency of reported adverse events was
      similar before and with irbesartan. CONCLUSION: In children with chronic kidney
      disease the effects of the angiotensin II antagonist irbesartan on arterial
      pressure and proteinuria mimic those observed with the converting enzyme
      inhibitors. The effectiveness of a single daily dose and the paucity of side
      effects suggest that angiotensin II antagonists expand therapeutic options for
      inhibiting the renin-angiotensin-aldosterone system in children.

PMID- 10968238
TI  - Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in
      childhood: a report of ten cases and review of the literature.
AB  - Chronic recurrent multifocal osteomyelitis is a rare chronic inflammatory
      musculoskeletal process observed in children and young adults. Recently, the
      acronym SAPHO syndrome (for synovitis, acne, pustulosis, hyperostosis, osteitis)
      was coined to emphasise the association between osteo-articular inflammations and
      different skin abnormalities which are aseptic and filled with neutrophils. In
      adults, chronic recurrent multifocal osteomyelitis is now a classical
      manifestation of SAPHO syndrome. Chronic skin disorders were seen in eight of ten
      children on follow-up at the University Children's Hospitals in Bern and Zurich
      and in 61 of 260 paediatric cases reported in the literature. The different skin
      lesions were palmoplantar pustulosis (n = 40), non-palmoplantar pustulosis (n =
      6), psoriasis vulgaris (n = 16) or severe acne (n = 4). More rarely Sweet
      syndrome (n = 2) or pyoderma gangrenosum (n = 1) were reported. CONCLUSION: The
      synovitis, acne, pustulosis, hyperostosis, osteitis syndrome is pertinent even in
      paediatrics since skin involvement is frequent.

PMID- 10968240
TI  - Adolescents' drug use and drug knowledge.
AB  - Self-medication is a common event. To use drugs correctly, a basic knowledge
      about drugs is required. Poor data are available about adults' drug knowledge.
      Furthermore, adolescents' basic drug knowledge has not been investigated. This
      study was designed in order to explore adolescents' drug use and knowledge and
      the factors that influence them. A total of 56 tenth grade students between 15-17
      years of age at a secondary school in Dresden, Germany were enrolled in a pilot
      study by answering a self-completion questionnaire. Of adolescents, 57% took from
      one to six different drugs in the 2 weeks before questioning. In particular, a
      chronic consumption of non-opioid analgesics was found. Some 15% of adolescents
      took headache remedies at least several times per month. Self-acquisition
      occurred more often for these drugs than for any other drug group. The best score
      for drug knowledge was 10 out of 13 possible points and only 43% of students
      attained from 7 to 10 points. Astonishingly, more than two-thirds of adolescents
      could not describe in their own words how a medicinal agent is ingested. Female
      gender and a chronic drug consumption were detected as influencing factors of
      better drug knowledge. CONCLUSION: The results indicate that adolescents gain
      drug knowledge through drug consumption and not before taking drugs. This leads
      to a potential risk particularly in the case of self-medication.

PMID- 10968239
TI  - Drinking behaviour among teenagers in Switzerland and correlation with
      lifestyles.
AB  - Several criteria (frequency, hazardous use, drunkenness) were used to delineate
      four distinct groups and to analyse the relations between patterns of alcohol use
      and other health variables. In the 1993 Swiss Multicentre Adolescent Survey on
      Health, anonymous self-administered questionnaires were distributed to a national
      representative sample of in-school 15 to 20-year-old adolescents. Of the
      respondents, 25% answered a module targeting alcohol use (n = 2359) of whom 13%
      were totally abstinent, 55.1% were moderate drinkers (< or = 1 drink/week and < 3
      times drunk), 21.7% were 'social' drinkers (> 3 times drunk and < twice driven
      when drunk) and 10.2% were 'problem drinkers' (> twice driven whilst drunk or > 1
      drink/day). Differences between problem drinkers and the rest of the sample
      showed the former as being predominantly boys with an odds ratio (OR) of 6.3,
      having a higher lifetime prevalence rate of cannabis use (OR = 3.4), never using
      seat belts (OR = 2.5), having their family/peers more often involved in alcohol
      consumption (OR = 1.9), being predominantly apprentices (against high school
      pupils OR = 1.9), having cheated during courses (OR = 1.9), being a member of a
      gang (OR = 1.7), having stolen in a public area (OR = 1.7) and having considered
      suicide (OR = 1.8). CONCLUSION: Within the Swiss context, whereas
      moderate/occasional use of alcohol must be considered as part of an adolescents'
      development, regular use of alcohol, often associated with drunkenness and
      driving while drunk, is associated with various health hazards and problems.
      Preventive strategies should be built accordingly.

PMID- 10968241
TI  - Osteogenesis imperfecta: profiles of motor development as assessed by a postal
      questionnaire.
AB  - This study was performed to achieve more detailed information regarding the age
      and sequence in the development of motor milestones in the different types of
      osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI
      were sent a questionnaire regarding the age at which patients achieved motor
      milestones. All patients were attending the outpatient clinic for children with
      OI at the Wilhelmina Children's Hospital. The motor milestones were classified
      into static motor milestones and dynamic motor milestones and all data were
      checked with health care records. The age of development of motor milestones was
      compared to reference values of the healthy population. The severity of the
      disease was classified according to Sillence based on clinical, genetic and
      radiological data. The age of intramedullary rodding of the first nail in the
      lower and upper extremity and the localisation was noted. A total of 76 parents
      responded to the 98 questionnaires (78%). In OI type I, a delay exists in
      achieving motor milestones, comparable to the 95th percentile of the normal
      population. In type III, the development of all motor milestones was
      significantly delayed compared to types I and IV with a discrepancy between
      static and dynamic milestones. In OI type IV, a retardation in motor development
      developed after the milestone 'sitting without support' was achieved. Motor
      development in types I and IV was not influenced by intramedullary rodding of the
      lower extremities, since rodding was rarely performed before the milestone
      'unsupported standing' was achieved. In type III, the influence of intramedullary
      rodding on the age of achieving motor milestones remains questionable.
      CONCLUSION: The severity of osteogenesis imperfecta has a large influence on the
      age and sequence in the development of motor milestones. No influence of
      intramedullary rodding of the lower extremities on motor development was found in
      osteogenesis imperfecta types I and IV, whereas the influence in type III remains
      questionable.

PMID- 10968242
TI  - Cystic adenomatoid malformation of the lung: clinical evolution and management.

PMID- 10968243
TI  - Neonatal thrombocytopenia.

PMID- 10968244
TI  - Do recombinant human erythropoietin and iron supplementation increase the risk of
      retinopathy of prematurity?
AB  - Comparing a group of infants treated with recombinant erythropoietin and iron
      supplementation to a group of control infants, no difference was observed
      concerning the transfusion need. The incidence of retinopathy of prematurity was
      significantly higher in the treated group. These data need to be confirmed in
      randomized controlled studies.

PMID- 10968245
TI  - Benign hypermobility syndrome in Greek schoolchildren.
AB  - Since the incidence of benign hypermobility syndrome is significantly high in
      otherwise healthy children, paediatricians should consider this benign entity
      when they evaluate musculoskeletal complaints in childhood.

PMID- 10968246
TI  - A case of neonatal-onset carbamoyl-phosphate synthase I deficiency treated by
      continuous haemodiafiltration.
AB  - This is the first case of fulminant neonatal-onset carbamoyl-phosphate synthase I
      deficiency treated by continuous hemodiafiltration indicating that this is an
      available and effective procedure for neonates with hyperammonemic coma.

PMID- 10968247
TI  - A case of sensory neuropathy associated with childhood Sjogren syndrome.
AB  - Complications observed in adulthood Sjogren syndrome also occur in the childhood
      disease and suggest that Sjogren syndrome should be considered as a cause of
      neuropathy in children. Treatment with corticosteroid is a choice for such cases.

PMID- 10968248
TI  - Wolcott-Rallison syndrome: a case with endocrine and exocrine pancreatic
      deficiency and pancreatic hypotrophy.
AB  - Clinical analysis and genetic investigations of new cases of Wolcott-Rallison
      syndrome are needed to evaluate the role of the gene(s) directly or indirectly
      implicated in pancreas development and in the aetiology of the syndrome.

PMID- 10968249
TI  - Impaired interleukin-2 production in T-cells from a patient with Wiskott-Aldrich
      syndrome: basis of clinical effect of interleukin-2 replacement therapy.
AB  - Interleukin-2 production may be one of the underlying causes of Wiskott-Aldrich
      syndrome immunodeficiency and recombinant interleukin-2 administration (or an
      infusion of T-cells expanded by CD3 stimulation and rIL-2) is able, to some
      extent, to restore defective T-cell function.

PMID- 10968250
TI  - A new look at the nuclear matrix.
AB  - The concept of the nuclear matrix, a karyoskeletal structure that serves as a
      support for the genome and its activities, has stimulated many studies of the
      association of nuclear components and functions with this structure. However,
      certain experimental findings are not consistent with the existence of the
      nuclear matrix in vivo, including our inability to visualise a corresponding
      structure in intact cells, the demonstrated mobility in vivo of chromatin and
      messenger ribonucleoprotein particles, which are claimed to be bound to the
      nuclear matrix, the paradoxical extractability from nuclei in low ionic strength
      buffers of enzymes that are found in the 2 M NaCl-insoluble matrix, and the
      extractability, in conditions which reproduce the intranuclear milieu, of regions
      of DNA (matrix or scaffold attachment regions, MAR/SARs) postulated to be bound
      to the nuclear matrix in vivo. This review considers the nuclear matrix model in
      the light of sometimes overlooked evidence that each step in its isolation may
      cause nuclear components to bind to it by new liaisons that do not exist in vivo.
      This is illustrated by experiments where nuclear-targeted green fluorescent
      protein is found in the nuclear matrix, and raises the possibility that MAR/SARs
      actually bind to DNA-binding proteins or multiprotein complexes, including
      replicational, transcriptional and processing machinery, and topoisomerases that
      are incorporated into the nuclear matrix during its preparation. Considering that
      the nuclear lamina forms a rigid exoskeleton, the necessity for internal skeletal
      structures is raised; the major roles that macromolecular crowding, phase
      partitioning, and charge effects are likely to play in organisation of the
      intranuclear space may provide new models for the compartmentalisation of
      proteins and functions into different nuclear domains and of chromosomes into
      territories.

PMID- 10968251
TI  - Double-strand breaks on artificial chromosomes in yeast.
AB  - Yeast artificial chromosomes composed primarily of bacteriophage gamma DNA
      exhibit very low levels of meiotic crossing over compared with similarly sized
      intervals of natural yeast DNA. When these recombinationally quiet chromosomes
      were augmented with a 12.5 kb insert of sequences from yeast chromosome VIII,
      genetic studies demonstrated that the artificial chromosomes had acquired
      recombination properties characteristic of this region of chromosome VIII. On
      authentic yeast chromosomes, most meiotic recombination events are initiated at
      sites where the DNA is cleaved to create a double-strand break (DSB). This report
      describes physical analyses that were carried out to examine the relationship
      between DSB sites and the recombination behavior of the artificial chromosomes.
      The results show that DSBs are rare on these artificial chromosomes, except for
      the 12.5 kb insert. Mapping of the DSB sites shows that their positions correlate
      with the previously determined positions of DSB sites on chromosome VIII.
      Deletion of two characterized chromosome VIII DSB sites from the 12.5 kb insert
      on the artificial chromosome resulted in the loss of the predicted DSB fragments
      and a reduction in crossing over between artificial chromosomes.

PMID- 10968252
TI  - Premitotic chromosome individualization in mammalian cells depends on
      topoisomerase II activity.
AB  - When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging
      topo II inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2
      phase. In this study, we analyzed chromosome structure in cells that bypassed
      this checkpoint. We observed a novel type of chromosome aberration, which we call
      omega-figures. These are entangled chromosome regions that indicate the
      persistence of catenations between nonhomologous sequences. The number of omega
      figures per cell increased sharply as cells evaded the transient block imposed by
      the topo II-dependent checkpoint, and the presence of caffeine (a checkpoint
      evading agent) potentiated this increase. Thus, the removal of nonreplicative
      catenations, a process that promotes chromosome individualization in G2, may be
      monitored by the topo II-dependent checkpoint in mammals.

PMID- 10968253
TI  - Molecular cytogenetic analyses and phylogenetic studies in the Nicotiana section
      Tomentosae.
AB  - Phylogenetic schemes based on changing DNA sequence have made a major impact on
      our understanding of evolutionary relationships and significantly built on
      knowledge gained by morphological and anatomical studies. Here we present another
      approach to phylogeny, using fluorescent in situ hybridisation. The phylogenetic
      scheme presented is likely to be robust since it is derived from the chromosomal
      distribution of ten repetitive sequences with different functions and
      evolutionary constraints [GRS, HRS60, NTRS, the Arabidopsis-type telomere repeat
      (TTTAGGG)n, 18S-5.8S-26S ribosomal DNA (rDNA), 5S rDNA, and four classes of
      geminiviral-related DNA (GRD)]. The basic karyotypes of all the plant species
      investigated Nicotiana tomentosiformis, N. kawakamii, N. tomentosa, N. otophora,
      N. setchellii, N. glutinosa (all section Tomentosae), and N. tabacum (tobacco,
      section Genuinae) are similar (x=12) but the distribution of genic and non-genic
      repeats is quite variable, making the karyotypes distinct. We found sequence
      dispersal, and locus gain, amplification and loss, all within the regular
      framework of the basic genomic structure. We predict that the GRD classes of
      sequence integrated into an ancestral genome only once in the evolution of
      section Tomentosae and thereafter spread by vertical transmission and speciation
      into four species. Since GRD is similar to a transgenic construct that was
      inserted into the N. tabacum genome, its fate over evolutionary time is
      interesting in the context of the debate on genetically modified organisms and
      the escape of genes into the wild. Nicotiana tabacum is thought to be an
      allotetraploid between presumed progenitors of N. sylvestris (maternal, S-genome
      donor) and a member of section Tomentosae (T-genome donor). Of section
      Tomentosae, N. tomentosiformis has the most similar genome to the T genome of
      tobacco and is therefore the most likely paternal genome donor. It is known for
      N. tabacum that gene conversion has converted most 18S-5.8S-26S rDNA units of N.
      sylvestris origin into units of an N. tomentosiformis type. Clearly if such a
      phenomenon were widespread across the genome, genomic in situ hybridisation
      (GISH) to distinguish the S and T genomes would probably not work since
      conversion would tend to homogenise the genomes. The fact that GISH does work
      suggests a limited role for gene conversion in the evolution of N. tabacum.

PMID- 10968254
TI  - XMR is associated with the asynapsed segments of sex chromosomes in the XY body
      of mouse primary spermatocytes.
AB  - The XMR (Xlr-related, meiosis-regulated) protein is an M(r) 30,000 nuclear
      protein closely associated with the XY body in mouse primary spermatocytes. It
      shows sequence similarity with several other meiosis-specific proteins. In the
      present study, we investigated the fine immunolocalization of XMR in the XY body
      by laser confocal and electron microscopy. It was found that XMR was associated
      with the asynapsed segments of sex chromosomes, including their axes and the
      surrounding chromatin loops. In contrast, the pseudoautosomal region and the
      opposite free end of the X were unlabeled for XMR. In mice with the reciprocal
      T(X;16)16H translocation, XMR was also associated with the heterochromatic
      translocation product that emerges from the XY body. These findings at the
      subchromosomal level point to a role for XMR in chromatin condensation and
      transcriptional inactivation. XMR is unique among proteins in being capable of
      association with the XY body. It could play a specific role in a mechanism of
      male X-chromosome inactivation in mammals.

PMID- 10968255
TI  - Non-apoptotic chromosome condensation induced by stress: delineation of
      interchromosomal spaces.
AB  - Chromosomes are known to occupy distinct territories, suggesting the existence of
      definite borders. Visualization of these borders requires chromatin condensation
      like that seen in prophase cells. We developed a novel method to induce
      chromosome condensation in all cells regardless of cell cycle stage using a
      complex set of stresses. The cells were not apoptotic, as indicated by the
      absence of DNA damage, maintenance of the intact lamina and scaffold attachment
      factor A, and by the continuation of metabolic processes as well as proliferative
      capacity. That the appearance of chromosome condensation did not represent a
      premature mitotic event was shown by the absence of fibrillarin and Ki67
      envelopment of chromosomes, continued protein synthesis and the reversibility of
      chromosome condensation. That chromosome condensation was achieved was
      demonstrated by the removal of chromatin from the nuclear envelope and chromosome
      painting. Specific genetic sites known to be at the surface of chromosomes
      retained their positions as shown by in situ hybridization. Stress-induced
      chromosome condensation was used to prove that specific nuclear domains such as
      ND10 are interchromosomally located and that green fluorescent protein-tagged
      ND10-associated proteins are useful markers for chromosomal boundaries after
      adenovirus 5 track formation in vivo. From these observations we conclude that
      chromosomal territories appear to have boundaries that exclude developing
      macromolecular aggregates.

PMID- 10968256
TI  - Probing meiosis in hybrids of Lolium (Poaceae) with a discriminatory repetitive
      genomic sequence.
AB  - A moderately repetitive genomic DNA sequence (designated pLPBB2-123) derived from
      Lolium perenne L. (Poaceae) is considerably more abundant in the genome of this
      species than in that of the closely related L. temulentum. The repetitive
      sequence probe is clearly able to discriminate between the genomic DNA of both
      species in Southern analysis, and effectively 'paints' only the chromosome set of
      L. perenne in diploid and triploid hybrids with L. temulentum. Fluorescence in
      situ hybridisation of this sequence onto homologous chromosomes during meiosis I
      of the hybrids shows that the sequence is evenly distributed along all of the
      chromosomes of L. perenne and appears to have little effect on the structural
      integrity or recombination potential of hybrid bivalents. Discrimination between
      chromatin of different parental origin in hybrid bivalents shows for the first
      time a progressive relaxation of relational coiling of homoeologues throughout
      meiotic prophase. It also highlights structural irregularities that can now be
      unequivocally assigned to the longer chromosomes of L. temulentum. The advantages
      of the use of specific differentially amplified sequences instead of whole genome
      probes are discussed within the context of introgression breeding programmes
      within the Lolium/Festuca complex.

PMID- 10968257
TI  - Cre/lox-mediated recombination in Arabidopsis: evidence for transmission of a
      translocation and a deletion event.
AB  - Cre recombinase was used to mediate recombination between a chromosomally
      introduced loxP sequence in Arabidopsis thaliana (35S-lox-cre) and transferred
      DNA (T-DNA) originating from Agrobacterium tumefaciens (plox-npt), carrying a
      single loxP sequence. Constructs were designed for specific Cre-mediated
      recombination between the two lox sites, resulting in restoration of neomycin
      phosphotransferase (nptII) expression at the target locus. Kanamycin resistant
      (Km(r)) recombinants were obtained with an efficiency of about 1% compared with
      random integration. Molecular analyses confirmed that these were indeed due to
      recombination between the lox sites of the target and introduced T-DNA. However,
      polymerase chain reaction analysis revealed that these reflected site-specific
      integration events only in a minority (4%). The other events were classified as
      translocations/inversions (71%) or deletions (25%), and were probably caused by
      site-specific recombination between a randomly integrated T-DNA and the original
      target locus. We studied some of these events in detail, including a Cre-mediated
      balanced translocation event, which was characterized by a combination of
      molecular, genetic and cytogenetic experiments (fluorescence in situ
      hybridization to spread pollen mother cells at meiotic prophase I). Our data
      clearly demonstrate that Agrobacterium-mediated transfer of a targeting T-DNA
      with a single lox site allows the isolation of multiple chromosomal
      rearrangements, including translocation and deletion events. Given that the
      complete sequence of the Arabidopsis genome will have been determined shortly
      this method has significant potential for applications in functional genomics.

PMID- 10968258
TI  - The design and synthesis of a potent Angiotensin II cyclic analogue confirms the
      ring cluster receptor conformation of the hormone Angiotensin II.
AB  - The novel amide linked Angiotensin II potent cyclic analogue, c-[Sar1,Lys3,Glu5]
      ANG II 19 has been designed and synthesized in an attempt to test the aromatic
      ring clustering and the charge relay bioactive conformation we have recently
      suggested for ANG II. This constrained cyclic analogue was synthesized by
      connecting the Lys3 amino and Glu5 carboxyl side chain groups, and it was found
      to be potent in the rat uterus assay and in anesthetized rabbits. The central
      part of the molecule is fixed covalently in the conformation predicted according
      to the backbone bend conformational model proposed for Angiotensin II. The
      obtained results using a combination of 2D NMR, 1D NOE spectroscopy and molecular
      modeling revealed a similar Tyr4-Ile5-His6 bend, a His6-Pro7 trans configuration
      and a side chain aromatic ring cluster of the key aminoacids Tyr4, His6, Phe8 for
      c-[Sar1,Lys3,Glu5] ANG II as it has been found for ANG II (Matsoukas, J. H.;
      Hondrelis, J.; Keramida, M.; Mavromoustakos, T.; Markriyannis, A.; Yamdagni, R.;
      Wu, Q.; Moore, G. J. J. Biol. Chem. 1994, 269, 5303). Previous study of the
      conformational properties of the Angiotensin II type I antagonist [Hser(gamma
      OMe)8] ANG II (Matsoukas, J. M.; Agelis, G.; Wahhab, A.; Hondrelis, J.;
      Panagiotopoulos. D.; Yamdagni, R.; Wu, Q.; Mavromoustakos, T.; Maia, H.; Ganter,
      R.; Moore, G. J. J. Med. Chem. 1995, 38, 4660) using 1-D NOE spectroscopy coupled
      with the present study of the same type of lead antagonist Sarilesin revealed
      that the Tyr4-Ile5-His6 bend, a conformational property found in Angiotensin II
      is not present in type I antagonists. The obtained results provide an important
      conformational difference between Angiotensin II agonists and type I antagonists.
      It appears that our synthetic attempt to further support our proposed model was
      successful and points out that the charge relay system and aromatic ring cluster
      are essential stereoelectronic features for Angiotensin II to exert its
      biological activity.

PMID- 10968259
TI  - Building a common feature hypothesis for thymidylate synthase inhibition.
AB  - A set of 21 highly flexible competitive inhibitors of thymidylate synthase (TS;
      EC 2.1.1.45) covering a wide activity range (IC50 = 6 nM-100 microM) has been
      investigated by three-dimensional quantitative structure-activity relationship
      (3D-QSAR). CATALYST was used to generate three-dimensional hypotheses to study
      the common interaction features among a set of thymidylate synthase inhibitor.
      The verification of the hypothesis was achieved by using the molecules outside
      the training set.

PMID- 10968260
TI  - Avermectin chemistry and action: ester- and ether-type candidate photoaffinity
      probes.
AB  - Avermectin B1a (1) is a potent anthelmintic, insecticide, miticide and chloride
      channel activator on interaction with a specific nerve membrane site analyzed by
      binding assays with [3H]1. Candidate photoaffinity probes were prepared replacing
      the dioleandrosyl substituent with potential isosteric esters and ethers
      approximating the original overall atom length and terminating in a phenyl moiety
      substituted with azido, iodo or hydroxy. Several of the candidates met the goal
      of high potency on mouse, housefly and fruit fly brain chloride channels with
      IC50 values of 7-57 nM in competing for the [3H]1 binding site.

PMID- 10968261
TI  - Chemical investigation of Mycale mytilorum and a study on toxicity and
      antidiabetic activity of 5-octadecylpyrrole-2-carboxaldehyde.
AB  - Chemical investigation of Mycale mytilorum afforded four new and two known
      compounds, of which 5-octadecylpyrrole-2-carboxaldehyde (1) and (6'Z)-5-(6'
      heneicosenyl) pyrrole-2-carboxaldehyde (2, congeners of alkylpyrrole
      carboxadehyde), (2S,3R,4E)-1,3-dihydroxy-2-[(heneicosanoyl) amino]-4-heneicosene
      (5, sphingolipid) and 2-methyl-3-(4,5,7-trihydroxy-8-hydroxy-methyltetrahydro-6H
      4-py ranyl)-2-propenoic acid (6, tetrahydropyran derivative) are new, and
      batylalcohol (3) and p-hydroxyphenylacetic acid (4) are known. The toxicity and
      antidiabetic activity of 5-octadecylpyrrole-2-carboxaldehyde were evaluated for
      the first time. Also, compounds 1, 2, 5 and 6 were studied for the antibacterial,
      antifungal and antiviral activity.

PMID- 10968262
TI  - Reactions of a series of 1-aminobenzimidazoles and 1-amino-3
      methylbenzimidazolium chlorides with 2,4-pentanedione.
AB  - Reactions of a series of 1-aminobenzimidazoles and 1-amino-3
      methylbenzimidazolium chlorides with 2,4-pentanedione were carried out and
      pyridazino[1,6-a]benzimidazoles and 2-pyrazolylanilines were generated. The
      product ratios of these compounds remarkably depended on the reaction conditions
      and on the electronic character of the substituent at the benzene moiety. The
      possible mechanisms involved in these reactions are discussed.

PMID- 10968263
TI  - Orally active cephalosporins: synthesis, structure-activity relationships and
      oral absorption of 3-[(E) and (Z)-2-substituted vinyl]-cephalosporins.
AB  - A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamid o]-3-[(E)-
      and (Z)-2-substituted vinyl]-3-cephem-4-carboxylic acids was designed and
      synthesized using palladium-catalyzed coupling reactions of a 3
      methanesulfonyloxy-3-cephem and an E substituted vinyl stannane or Wittig
      reaction of a 3-triphenylphosphoniummethyl cephem and an aldehyde as a key step.
      These compounds were evaluated for in vitro antibacterial activity and oral
      absorption in rats. A number of them exhibited excellent antibacterial activity
      against both gram-positive and gram-negative bacteria including Haemophilus
      influenzae. Among them, FR86524 (2j). having a (Z)-2-(3-pyridyl)vinyl moiety at
      the C-3 position, had the most well balanced activity. Although FR86254 exhibited
      low oral absorption, the pivaloyloxymethyl ester (23) of FR86524 showed improved
      oral absorption.

PMID- 10968264
TI  - Novel adenosine A1 receptor antagonists. Synthesis and structure-activity
      relationships of a novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6
      yl)-2-phenylpyrazolo[1,5 -a]pyridines.
AB  - A novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2
      phenylpyrazol o[1,5-a]pyridines was synthesized and evaluated for in vitro
      adenosine A1 and A2A receptor binding activities. Most of the cyclohexenyl
      derivatives (7a-e, 8a-s) were found to be potent adenosine A1 receptor
      antagonists. In a series of analogues of FR166124 (3a), alcohol 7c, nitrile 7e
      and amide derivatives (7d, 8c, 8r) were found to be more potent A1 antagonists
      with higher A2A/A1 selectivity than FR166124. Amongst them, 8r showed
      considerable water solubility (33.3 mg/mL), but lower than that of the sodium
      salt of FR166124 (> 200 mg/mL). Additionally, FR166124 had strong diuretic
      activity by both p.o. and iv administration in rats (minimum effective dose=0.1
      and 0.032 mg/kg, respectively).

PMID- 10968265
TI  - Radiolabeling of paclitaxel with electrophilic 123I.
AB  - 123I-Labeled paclitaxel, [123I]-1 was prepared by electrophilic aromatic
      radioiodination of 3'-N-(p-trimethylstannylbenzoyl)-3'-debenzoylpaclitaxel 2 with
      123I- in the presence of peracetic acid.

PMID- 10968266
TI  - Alumina-supported synthesis of antibacterial quinolines using microwaves.
AB  - 7-(5'-Alkyl-1',3',4'-thiadiazol/oxadiazol-2'-ylthio)-6 -fluoro-2,4
      dimethylquinolines and 3-formyl-2-(2'-hydroxy- 1',4'-naphthoquinon-3'-yl)-4
      methyl/6-methyl/7-quinolines have been synthesised by the reaction of 5-alkyl
      1,3,4-thiadiazol/oxadiazol-2-thiols with 7-chloro-6-fluoro-2,4-dimethylquinoline
      and by the reaction of 2-hydroxy-1,4-naphthoquinone with 2-chloro-3-formyl-4
      methyl/6-methyl/7-methyl/8-methylquinolines respectively on basic alumina using
      microwaves, the reaction time has been brought down from hours to seconds with
      improved yield as compared to conventional heating. The compounds were tested for
      their in vitro antibacterial activity. All compounds showed promising
      antibacterial activity. The best activity was observed by compounds 3a and 3f.

PMID- 10968267
TI  - Antimicrobial effects of novel siderophores linked to beta-lactam antibiotics.
AB  - As a strategy to increase the penetration of antibiotic drugs through the outer
      membrane of gram-negative pathogens, facilitated transport through siderophore
      receptors has been frequently exploited. Hydroxamic acids, catechols, or very
      close isosteres of catechols, which are mimics of naturally occurring
      siderophores, have been used successfully as covalently linked escorting
      moieties, but a much wider diversity of iron binding motifs exists. This
      observation, coupled to the relative lack of specificity of siderophore
      receptors, prompted us to initiate a program to identify novel, noncatechol
      siderophoric structures. We screened over 300 compounds for their ability to (1)
      support growth in low iron medium of a Pseudomonas aeruginosa siderophore
      biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore
      antibiotic conjugate for siderophore receptor access. From these assays we
      identified a set of small molecules that fulfilled one or both of these criteria.
      We then synthesized these compounds with functional groups suitable for
      attachment to both monobactam and cephalosporin core structures. Siderophore-beta
      lactam conjugates then were tested against a panel of Escherichia coli,
      Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of
      the resultant chimeric compounds had antimicrobial activity approaching that of
      ceftazidime, and most compounds demonstrated very potent activity against their
      cellular targets, only a single compound was obtained that had enhanced,
      siderophore-mediated antibacterial activity. Results with tonB mutants frequently
      showed increased rather than decreased susceptibilities. suggesting that multiple
      factors influenced the intracellular concentration of the drugs.

PMID- 10968268
TI  - Trypanothione reductase inhibition/trypanocidal activity relationships in a 1,4
      bis(3-aminopropyl)piperazine series.
AB  - A series of symmetrically substituted 1,4-bis(3-aminopropyl)piperazines was
      synthesized and tested towards trypanothione reductase and for its in vitro
      trypanocidal potency. The most trypanocidal amongst them was found to be totally
      inactive towards the enzyme and thus constitutes a lead structure for the
      identification of new potential Trypanosoma cruzi target(s).

PMID- 10968269
TI  - Substituted oxygenated heterocycles and thio-analogues: synthesis and biological
      evaluation as melatonin ligands.
AB  - A new series of substituted oxygenated heterocycles and thio-analogues were
      synthesized and evaluated as melatonin receptor ligands. The replacement of the
      indolic moiety of melatonin by heterocyclic skeleton such as 1,4-benzodioxin, 2,3
      dihydro-1,4-benzodioxin, chroman, 2,3-dihydro-1,4-benzoxathiin, thiochroman,
      carrying the amidic chain on the aromatic ring, leads to compounds showing a weak
      affinity for melatonin receptors, except for the compounds 1cb and 1hb.

PMID- 10968270
TI  - Formation of a phospholipid-linked pyrrolecarbaldehyde from model reactions of D
      glucose and 3-deoxyglucosone with phosphatidyl ethanolamine.
AB  - Phospholipid-linked 'advanced glycation end products' (AGEs) are supposed to play
      an important role for lipid oxidation in vivo. The identification of the
      pyrrolecarbaldehyde 1-[2-formyl-5-(hydroxymethyl)-1 H-pyrrol-1-yl]-4,10-dioxo-7
      (tetradecanoyloxy)-3,5,9-trioxa- 4lambda5-phosphatricosan-4-olate (7) from model
      reactions of D-glucose or 3-deoxyglucosone (4, 3-DG) with phosphatidyl
      ethanolamine (PE) is described. A preparation method is given for 1-(2
      hydrox?ethyl)-5-(hydroxymethyl)-1H-pyrrole-2-carbaldehyde (8). Independent
      syntheses as well as unequivocal structural characterization are reported for the
      substitution products of 8 1-(2-hydroxyethyl)-5-(methoxymethyl)-1H-pyrrole-2
      carbaldehyde (9a) and 5-(ethoxymethyl)-1-(2-hydroxyethyl)-1H-pyrrole-2
      carbaldehyde (9b). For all these compounds, chromatographic and spectroscopic
      data were established by GLC-MS and HPLC with diode array detection (DAD). PE and
      D-glucose or 3-DG 4 were either incubated at pH 7.4, 100 degrees C for 3 h or at
      pH 7.4, 37 degrees C for 5 weeks in neat buffer or ethanol buffer mixtures. The
      phospholipid fraction was purified on a C18 solid-phase extraction column and
      cleaved with ethanolic potassium hydroxide. The carbaldehyde 8, released in this
      process, was identified bs GLC-MS and quantified by HPLC-DAD. Formation of 7 is
      favored in the ethanol buffer reactions relative to those in buffer solution only
      although the amounts determined from the 37 degrees C incubations generally are
      very low. It seems likely, therefore, that phospholipid-linked
      pyrrolecarbaldehydes, such as 7, are biomarkers rather than effectors of membrane
      damage in vivo.

PMID- 10968271
TI  - Efficient synthesis and biological evaluation of all A-ring diastereomers of
      1alpha,25-dihydroxyvitamin D3 and its 20-epimer.
AB  - An improved synthesis of the diastereomers of 1alpha,25-dihydroxyvitamin D3 (1)
      was accomplished utilizing our practical route to the A-ring synthon. We applied
      this procedure to synthesize for the first time all possible A-ring diastereomers
      of 20-epi-1alpha,25-dihydroxyvitamin D3 (2). Ten-step conversion of 1-(4
      methoxyphenoxy)but-3-ene (6), including enantiomeric introduction of the C-3
      hydroxyl group to the olefin by the Sharpless asymmetric dihydroxylation,
      provided all four possible stereoisomers of A-ring enynes (3). i.e., (3R,5R)-,
      (3R,5S)-, (3S,5R)- and (3S,5S)-bis[(tert-butyldimethylsilyl)oxy]oct-1-en-7-yne,
      in good overall yield. Palladium-catalyzed cross-coupling of the A-ring synthon
      with the 20-epi CD-ring portion (5), (E)-(20S)-de-A,B-8-(bromomethylene)cholestan
      25-ol, followed by deprotection, afforded the requisite diastereomers of 20-epi
      1alpha,25-dihydroxyvitamin D3 (2). The biological profiles of the synthesized
      stereoisomers were assessed in terms of affinities for vitamin D receptor (VDR)
      and vitamin D binding protein (DBP). HL-60 cell differentiation-inducing activity
      and in vivo calcium-regulating potency in comparison with the natural hormone.

PMID- 10968272
TI  - Synthesis and evaluation as glycosidase inhibitors of 2,5-imino-D-glucitol and
      1,5-imino-D-mannitol related derivatives.
AB  - Selectively functionalized 2,5-imino-D-glucitol and 1,5-imino-D-mannitol
      derivatives were synthesized and tested as precursors of hydrolytically resistant
      pseudo-disaccharides. Among them N-acetyl-6-amino-6-deoxy-2,5-imino-D-glucitol
      (11) and N-acetyl-6-amino-6-deoxy-1,5-imino-D-mannitol (12) were found potent and
      specific inhibitors against beta-D-glucosidase and alpha-L-fucosidase,
      respectively.

PMID- 10968273
TI  - Effects of the hydrophobicity of taxoids on their interaction with tubulin.
AB  - Modifications of the hydrophobic character at the 7 and 10 positions of the
      taxoids greatly modified the effect of these drugs on the tubulin microtubule
      system. The presence of an alkyl chain at these positions decreased the activity
      while their corresponding more polar analogues restored the activity of these
      molecules. It appears that the recognition of taxoids by tubulin depends on the
      location of the most important hydrophobic area.

PMID- 10968274
TI  - Synthesis, spectroscopic characterization and biological properties of new
      natural aldehydes thiosemicarbazones.
AB  - As part of a research programme aimed at the synthesis of compounds with
      antiviral, antibacterial and antitumor properties and their spectroscopic
      characterization, new thiosemicarbazones deriving from natural aldehydes have
      been investigated. These substances contain in the same molecule both a chain
      with nucleophilic centres N, S with tubercolostatic activity, and a glycosidic or
      alkyl moiety (modified glycosides and nucleosides have recently received a great
      deal of attention in the fields of neoplastic diseases and viral infections). In
      this paper the synthesis and the characterization of these compounds by means of
      1H NMR, IR, and MS techniques is reported. Biological studies have involved both
      inhibition of cell proliferation and apoptosis tests on human leukemia cell line
      U937.

PMID- 10968275
TI  - Synthesis of a small library of phenylalkylamide derivatives as melatoninergic
      ligands for human mt1 and MT2 receptors.
AB  - Focused small libraries of melatonin receptor ligands from arylalkylamine
      derivatives were synthesised by combinatorial chemistry using the mix and split
      method in the solid phase. A library of 108 compounds was then synthesised from
      12 arylalkyl amines and nine carboxylic acids. The compound mixtures were
      evaluated on chicken brain melatonin and recombinant human mt1 and MT2 receptors.
      Deconvolution of the most potent mixture demonstrated the superiority of 3
      methoxy and 2,5-dimethoxy substitution on the phenyl ring with isopropyl, propyl
      and ethyl amido chains. Several compounds with nanomolar affinity for human
      melatonin receptors were obtained.

PMID- 10968276
TI  - Monoalkylation of DNA by reductively activated FR66979.
AB  - The antitumor antibiotic FR66979 has previously been shown to form interstrand
      cross-links in duplex DNA at the sequence [5'-d(CG)]2, linking the exocyclic
      amino groups (N2) of deoxyguanosine (dG) residues. During the reaction of
      reductively activated FR66979 with DNA. products are formed which have
      electrophoretic mobility in denaturing polyacrylamide gels which is intermediate
      between that of unmodified and interstrand cross-linked DNA. We show here that
      these products are monoadducts between FR66979 and DNA and provide strong
      evidence for the site of alkylation being N2 of dG. Moreover, the sequence
      selectivity of monoalkylation reactions between FR66979 and DNA containing either
      5'-d(CG).5'-d(CI) or [5'-d(CG)]2 was observed to be ca. 5-fold less than for the
      related antitumor antibiotic mitomycin C (MC). The mechanistic implications of
      this result are discussed. Furthermore, it was demonstrated that contrary to a
      previous report, FR66979 requires DNA to be in duplex form for efficient
      monoadduct formation.

PMID- 10968277
TI  - The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)
      pyrazolo-[1 ,5-a]-pyrimidine: a corticotropin-releasing factor (hCRF1)
      antagonist.
AB  - Structure activity relationship studies led to the discovery of 4-(3-pentylamino)
      2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazo lo-[1,5-a]-pyrimidine 11-31
      (DMP904), whose pharmacological profile strongly supports the hypothesis that
      hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki =
      1.0+/-0.2 nM (n = 8)) was a potent antagonist of hCRF1-coupled adenylate cyclase
      activity in HEK293 cells (IC50= 10.0+/-0.01 nM versus 10 nM r/hCRF, n = 8); alpha
      helical CRF(9-41) had weaker potency (IC50 = 286+/-63 nM, n = 3). Analogue 11-31
      had good oral activity in the rat situational anxiety test; the minimum effective
      dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction
      in latency time in the dark compartment) was observed at this dose.
      Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The
      literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test.
      Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100
      mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good
      plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss
      values equal to 46.4+/-7.6 h. 0.49+/-0.08 L/kg/h and 23.0+/-4.2 L/kg,
      respectively. After oral dosing, the mean Cmax, Tmax t1/2 and bioavailability
      values were equal to 1260+/-290 nM, 0.75+/-0.25 h. 45.1+/-10.2 h and 33.1%,
      respectively. The overall rat behavioral profile of this compound suggests that
      it may be an anxiolytic drug with a low motor side effect liability.

PMID- 10968279
TI  - Ligand design for alpha1 adrenoceptor subtype selective antagonists.
AB  - Alpha1 adrenoceptors have three subtypes and drugs interacting selectively with
      these subtypes could be useful in the treatment of a variety of diseases. In
      order to gain an insight into the structural principles governing subtype
      selectivity, ligand based drug design (pharmacophore development) methods have
      been used to design a novel 1,2,3-thiadiazole ring D analogue of the aporphine
      system. Synthesis and testing of this compound as a ligand on cloned and
      expressed human alpha1 adrenoceptors is described. Low binding affinity was
      found, possibly due to an unfavourable electrostatic potential distribution.
      Pharmacophore models for antagonists at the three adrenoceptor sites (alpha1A,
      alpha1B, alpha1D) were generated from a number of different training sets and
      their value for the design of new selective antagonists discussed. The first
      preliminary antagonist pharmacophore model for the alpha1D adrenoceptor subtype
      is also reported.

PMID- 10968278
TI  - Synthesis and anti-HIV activity of cosalane analogues incorporating nitrogen in
      the linker chain.
AB  - Introduction of an amido group or an amino moiety into the alkenyl linker chain
      of cosalane (1) provided a new series of analogues 3-8. The new compounds were
      evaluated as inhibitors of the cytopathic effect of HIV-1 and HIV-2 in cell
      culture. The replacement of the 1' and 2' carbons in the linker chain of I by an
      amido group was generally tolerated. The length of the linker chain and the
      stereochemistry of the substituent at C-3 of the steroidal ring had significant
      effects on the antiviral activity and potency. Incorporation of an amino moiety
      into the linker completely abolished the anti-HIV activity. There are several
      steps in the HIV replication cycle that have been proposed as targets for the
      development of therapeutic agents (De Clercq, E. J. Med. Chem. 1995, 38, 2491; De
      Clercq, E. Pure Appl. Chem. 1998, 70, 567). However, currently approved anti-HIV
      drugs are only directed against the viral enzymes reverse transcriptase or
      protease (Carpenter. C. C. J.; Fischl, M. A.; Hammer, S. M.; Hirsch, M. S.;
      Jacobsen, D. M.; Katzenstein, D. A.; Montaner, J. S. G.; Richman, D. D.; Saag, M.
      S.; Schooley, R. T.; Thompson, M. A.; Vella, S.; Yeni, P. G.; Volberding, P. A.
      JAMA 1998, 280, 78). Drugs capable of interfering with other steps of the virus
      life cycle will be highly valuable in the antiretroviral therapy of AIDS, as they
      will have different patterns of resistance mutations than the drugs currently
      used clinically. In addition, their utilization in combination with other
      therapeutic agents could provide more potent drug 'cocktails' capable of
      completely suppressing virus replication. Consequently, there is an urgent need
      for the discovery of clinically useful anti-HIV agents possessing novel
      mechanisms of action.

PMID- 10968280
TI  - DNA double helix destabilizing properties of cyclobisintercaland compounds and
      competition with a single strand binding protein.
AB  - The DNA helix destabilizing activity of a series of cyclobisintercaland compounds
      (CBIs) has been evaluated by measuring their ability to displace a 32P-labelled
      oligonucleotide primer (17-mer) hybridized to the single stranded DNA of M13.
      This destabilizing activity appears to be strongly dependent on the cyclic
      structure (the linear acyclic references are inactive) and the size of the
      macrocycle; both features being known to determine the preferential binding of
      the compound to ssDNA. Interestingly, CBIs induced the dissociation of the duplex
      template in a concentration range (0.5-1 microM) close to that required for the
      destabilizing activity of single stranded DNA binding proteins (SSBs). Therefore
      competition experiments between CBIs and an SSB protein (Eco SSB) for binding to
      a single stranded oligonucleotide target (36-mer) have been performed through gel
      electrophoresis and nitrocellulose binding assays and strong inhibitory effects
      on the formation of the SSB:36-mer complex have been observed.

PMID- 10968281
TI  - Stereospecific syntheses of trans-vinyldioxidosqualene and 3-hydroxysulfide
      derivatives, as potent and time-dependent 2,3-oxidosqualene cyclase inhibitors.
AB  - trans-Vinyldioxidosqualene and beta-hydroxysulfide derivatives were synthesized
      stereospecifically and evaluated as inhibitors of animal and yeast oxidosqualene
      cyclases. Only trans-vinyldioxidosqualene and 2,3-epoxy-vinyl-beta
      hydroxysulfides, having the reactive function at crucial positions 14,15 and
      18,19, were active as inhibitors of animal and yeast cyclases. (14-trans)-28
      Methylidene-2,3: 14,15-dioxidoundecanorsqualene 27 was the most potent inhibitor
      of the series of pig liver cyclase, with an IC50 of 0.4 microM, and it behaved
      also as the most active time-dependent inhibitor of the animal enzyme.

PMID- 10968282
TI  - Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 6:
      hydrolysis of 7,8-diacetoxy-4-methylcoumarin by a novel deacetylase in rat liver
      microsomes--a simple method for assay and characterisation.
AB  - The existence of a novel microsomal deacetylase in rat liver catalysing
      deacetylation of diacetoxy 4-methylcoumarins has been reported. A simple method
      is outlined for the enzyme assay based upon the quantification of the dihydroxy
      derivative by measuring the UV absorption of its complex with ADP and Fe3+ at 600
      nm. The enzyme can be routinely assayed using 7,8-diacetoxy-4-methylcoumarin
      (DAMC) as the substrate and demonstrated hyperbolic kinetics and yielded Km and
      vmax values of 1250 microM and 500 units, respectively. The pH optima was found
      to be 7.5 for the enzyme. No DAMC deacetylase activity was found in hepatic
      cytosol and the enzyme activity was not discernible in extrahepatic tissues.

PMID- 10968283
TI  - Synthesis and biological activity of some rigid analogues of flavone-8-acetic
      acid.
AB  - Some rigid analogues of flavone-8-acetic acid are described. Direct in vitro
      toxicity of the synthesised compounds was evaluated towards four tumoral cell
      lines and the ability of these compounds to stimulate mouse peritoneal
      macrophages in culture to become tumoricidal (indirect toxicity) was also
      studied. All compounds were able to induce direct cytotoxicity only at very high
      concentrations but showed a remarkable indirect activity. In particular compound
      4d was able to significantly increase macrophage lytic properties and has been
      selected for further investigations.

PMID- 10968284
TI  - Pentacyclic triterpenoids from Freziera sp. that inhibit DNA polymerase beta.
AB  - In a survey of crude plant extracts for DNA polymerase 1 inhibitors, a methyl
      ethyl ketone extract prepared from Freziera sp. exhibited potent inhibition of
      DNA polymerase beta. Bioassay-guided fractionation of the extract, guided by an
      assay to detect DNA polymerase beta inhibition, resulted in the isolation of six
      active pentacyclic triterpenoids (1-6). These triterpenoids had IC50 values
      ranging from 7.5 to 16 microM in the presence of bovine serum albumin (BSA) and
      2.6-5.8 microM in the absence of BSA, consistent with the possibility that these
      inhibitors may be of use in vivo.

PMID- 10968285
TI  - Structure-activity relationship of piperine and its synthetic analogues for their
      inhibitory potentials of rat hepatic microsomal constitutive and inducible
      cytochrome P450 activities.
AB  - Inhibitors of drug metabolism have important implications in pharmaco-toxicology
      and agriculture. We have reported earlier that piperine, a major alkaloid of
      black and long peppers inhibits both constitutive and inducible cytochrome P450
      (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has
      been made to prepare several novel synthetic analogues so as to relate various
      modifications in the parent molecule to the inhibition of CYP activities. Two
      types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7
      methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were
      investigated in rat microsomal fraction prepared from untreated, 3MC- and PB-
      treated rat liver in vitro. Modifications were introduced into the piperine
      molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the
      basic moiety. Thus, 38 compounds have been subjected to such studies, and
      simultaneously an attempt has also been made to arrive at the structure-activity
      relationship of synthetic analogues. In general, most of the inhibitory potential
      of the parent molecule is lost with modification in either of the three
      components of piperine. Saturation of the side chain resulted in significantly
      enhanced inhibition of CYP while modifications in the phenyl and basic moieties
      in few analogues offered maximal selectivity in inhibiting either constitutive or
      inducible CYP activities. Thus few novel analogues as CYP inactivators have been
      synthesized which may have important consequences in pharmacokinetics and
      bioavailability of drugs.

PMID- 10968286
TI  - Interstrand disulfide cross-linking of internal sugar residues in duplex RNA.
AB  - Disulfide cross-linking is being used increasingly more to study the structure
      and dynamics of nucleic acids. We have previously developed a procedure for the
      formation of disulfide cross-links through the sugar-phosphate backbone of
      nucleic acids. Here we report the preparation and characterization of an RNA
      duplex containing a disulfide interstrand cross-link. A self-complementary
      oligoribonucleotide duplex containing an interstrand cross-link was prepared from
      the corresponding 2'-amino modified oligomer. Selective modification of the 2'
      amino group with an aliphatic isocyanate, containing a protected disulfide, gave
      the corresponding 2'-urea derivative in excellent yield. An RNA duplex containing
      an intrahelical, interstrand disulfide cross-link was subsequently prepared by a
      thiol disulfide exchange reaction in nearly quantitative yield as judged by
      denaturing polyacrylamide gel electrophoresis (DPAGE). The cross-linked RNA was
      further characterized by enzymatic digestion and the Structure of the cross-link
      lesion was verified by comparison to an authentic sample, prepared by chemical
      synthesis. The effect of the chemical modifications on duplex stability was
      determined by UV thermal denaturation experiments. The intrahelical cross-link
      stabilized the duplex considerably: the disulfide cross-linked oligomer had a
      melting temperature that was ca. 40 degrees C higher than that of the noncross
      linked oligomer.

PMID- 10968287
TI  - Stereo-enriched phosphorothioate oligodeoxynucleotides: synthesis, biophysical
      and biological properties.
AB  - Stereo-enriched [Rp] and [Sp]-phosphorothioate oligodeoxynucleotides are
      synthesized using oxazaphospholidine derivatized monomers. Three different
      designs of phosphorothioate oligodeoxynucleotides (PS-oligos), (i) stereo
      enriched all-[Rp] or all-[Sp] PS-linkages, (ii) stereo-random mixture of PS
      linkages, and (iii) segments containing certain number of stereo-enriched [Rp]
      and [Sp] PS-linkages ([Sp-Rp-Sp] or [Rp-Sp-Rp]), have been studied. Thermal
      melting studies of these PS-oligos with RNA complementary strands showed that the
      binding affinities are in the order [Rp] > [Sp-Rp-Sp]-[Rp-Sp-Rp] > stereo-random
      > [Sp]. Circular dichroism (CD) studies suggest that the stereochemistry of the
      PS-oligo does not affect the global conformation of the duplex. The in vitro
      nuclease stability of these PS-oligos is in the order [Sp] > [Sp-Rp-Sp] > stereo
      random > [Rp]. The RNase H activation is in the order [Rp] > stereo-random > [Rp
      Sp-Rp] > [Sp] > [Sp-Rp-Sp]. Studies in a cancer cell line of PS-oligos targeted
      to MDM2 mRNA showed that all oligos had similar biological activity under the
      experimental conditions employed. Protein- and enzyme-binding studies showed
      insignificant stereo-dependent binding to proteins. The [Sp] and [Sp-Rp-Sp]
      chimeric and stereo-random PS-oligos that contained a CpG motif showed higher
      cell proliferation than [Rp] PS-oligo of the same sequence.

PMID- 10968288
TI  - Asitrilobins C and D: two new cytotoxic mono-tetrahydrofuran annonaceous
      acetogenins from Asimina triloba seeds.
AB  - Two new bioactive mono-tetrahydrofuran (THF) gamma-lactone acetogenins,
      asitrilobins C (1) and D (2), were isolated from the seeds of Asimina triloba
      (Annonaceae) by directing the fractionation with brine shrimp lethality.
      Compounds 1 and 2 have a relative stereochemical relationship of
      threo/trans/threo across the mono-THF ring with its two flanking hydroxyls. Their
      structures were established on the basis of chemical and spectral evidence.
      Compounds 1 and 2 showed selective cytotoxicity comparable with adriamycin for
      the breast carcinoma (MCF-7) and the colon adenocarcinoma (HT-29) cell lines.

PMID- 10968289
TI  - Care for depression in HMO patients aged 65 and older.
AB  - OBJECTIVE: To examine treatment for depression among older adults in a large
      staff model health maintenance organization (HMO). DESIGN: A 4-year prospective
      cohort study (1989-1993). SETTING: Four primary care clinics of a large staff
      model HMO in Seattle, Washington. PATIENTS: A total of 2558 Medicare enrollees
      aged 65 and older. MAIN OUTCOME MEASURES: Treatment of depression was defined as
      primary care visits resulting in depression diagnoses, use of antidepressant
      medications, or specialty mental health services. MAIN RESULTS: The older adults
      in our sample had low rates of treatment for depression, ranging from 4 to 7% in
      the entire sample and from 12 to 25% among those with probable depressive
      disorders. Predictors of treatment included female gender, severity, and
      persistence of depressive symptoms, and severity of comorbid medical illness.
      Even when patients were treated for depression, the intensity of treatment was
      very low. Overall likelihood of treatment for depression increased somewhat from
      1989 to 1993, but among those treated, the rate of adequate antidepressant use
      remained below 30%. CONCLUSIONS: There is still considerable need to improve care
      for older adults with depression in primary care.

PMID- 10968290
TI  - Families' perception of the added value of hospice in the nursing home.
AB  - OBJECTIVE: To determine if family members perceive that hospice improves the care
      of dying nursing home residents during the last 3 months of life. DESIGN: Mailed
      survey. PARTICIPANTS: Family members for all nursing home hospice enrollees in
      North Carolina during a 6-month period. MEASUREMENTS: After residents' deaths,
      family members answered questions about the quality of care for symptoms before
      and after hospice, the added value of hospice, the effect of hospice on
      hospitalization, and special services provided by nursing home staff or by
      hospice staff. RESULTS: A total of 292 (73%) of 398 eligible family members
      completed surveys. The average age of the nursing home residents who had received
      hospice was 79.5 years; 50% had cancer and 76% were dependent for self-care. In
      their last 3 months, 70% of decedents had severe or moderate pain, 56% had severe
      or moderate dyspnea, and 61% had other symptoms. Quality of care for physical
      symptoms was rated good or excellent by 64% of family before hospice and 93%
      after hospice (P<.001). Dying residents' emotional needs included care for
      moderate or severe depression (47%), anxiety (50%), and loneliness (35%). Quality
      of care for emotional needs was rated good or excellent by 64% of family before
      hospice and 90% after hospice (P<.001). Fifty-three percent of respondents
      believed hospice prevented hospitalizations. Family estimated the median added
      value of hospice to be $75 per day and described distinct special services
      provided by hospice and by nursing home staff. CONCLUSIONS: Family members
      believe that nursing home hospice improves quality of care for symptoms, reduces
      hospitalizations, and adds value and services for dying nursing home residents.

PMID- 10968291
TI  - Physical activity, falls, and fractures among older adults: a review of the
      epidemiologic evidence.
AB  - OBJECTIVES: Assess the relationship between physical activity and risk for falls
      and osteoporotic fractures among older adults. DESIGN: Review and synthesis of
      published literature. MEASUREMENTS: We searched the literature using MEDLINE,
      Current Contents, and the bibliographies of articles identified. We included
      randomized controlled trials (RCT) of the effects of physical activity on the
      incidence of falls and case-control and prospective cohort studies of the
      association of physical activity with osteoporotic fracture risk. We also
      summarized mechanisms whereby physical activity may influence risk for falls and
      fractures. RESULTS: Observational epidemiologic studies and randomized clinical
      trials evaluating the effectiveness of physical activity programs to prevent
      falls have been inconclusive. However, many studies have lacked adequate
      statistical power, and recent trials suggest that exercise, particularly
      involving balance and lower extremity strength training, may reduce risk of
      falling. There is consistent evidence from prospective and case-control studies
      that physical activity is associated with a 20-40% reduced risk of hip fracture
      relative to sedentary individuals. The few studies that have examined the
      association between physical activity and risk of other common osteoporotic
      fractures, such as vertebral and wrist fractures, have not found physical
      activity to be protective. CONCLUSIONS: Epidemiologic studies suggest that higher
      levels of leisure time physical activity prevent hip fractures and RCTs suggest
      certain exercise programs may reduce risk of falls. Future research needs to
      evaluate the types and quantity of physical activity needed for optimal
      protection from falls and identify which populations will benefit most from
      exercise.

PMID- 10968292
TI  - Self-care practices used by older men and women to manage urinary incontinence:
      results from the national follow-up survey on self-care and aging.
AB  - OBJECTIVES: To estimate the extent to which self-care practices are employed by
      older adults with urinary incontinence (UI); to determine how demographic and
      functional status measures are associated with self-care practice use; and to
      explore the relationship between contacting a doctor and disposable pad use.
      DESIGN: A cross-sectional analysis of a national probability sample using
      multiple logistic regression. SETTING: Responses of subjects with UI (n = 787)
      from the 1993-1994 National Follow-up Survey on Self-Care and Aging, a follow-up
      survey of older Medicare beneficiaries living in the community within the
      contiguous United States drawn in 1990-1991 MEASURES: Subject responses about UI,
      fecal incontinence, dressing, eating, bathing, Instrumental Activities of Daily
      Living (IADL), Mobility Activities of Daily Living (MADL), age, gender, place of
      residence, race, education, proxy response to the survey, and self-reported
      medical conditions. RESULTS: Self-care practices used by more than 25% of
      respondents with UI included using disposable pads, limiting trips, and limiting
      fluids. Among older adults with incontinence, more women used disposable pads
      (44.5%; 95% CI, 36.9-52.1) and performed exercises (14.2%; 95% CI, 9.7-18.9) than
      did men (15.1%; 95% CI, 8.1-22.1; and 4.3%; 95% CI, 1.0-7.7, respectively). Bi
      variate analysis showed respondents with severe UI or fecal incontinence reported
      greater use of self-care practices. In multivariate models of the three most
      commonly used self-care practices, measures of UI severity were not always
      associated independently with self-care practice use, whereas ADL measures of
      functional status were. Disposable pad use was positively independently
      associated (OR 3.36; 95% CI, 2.01-5.63) in multivariate models with contacting a
      doctor about incontinence, even after controlling for age, gender, demographics,
      and self-reported medical conditions. CONCLUSIONS: Use by older adults of self
      care practices to manage urinary incontinence is predicted independently in
      multivariate models by measures of functional status such as dressing, eating,
      bathing, IADLs or MADLs, but not by all UI measures. Disposable pad users had
      increased odds of contacting a doctor, suggesting that self-care practices and
      formal medical care are not always inversely related.

PMID- 10968293
TI  - Using structured implicit review to assess quality of care in the Program of All
      Inclusive Care for the Elderly (PACE)
AB  - OBJECTIVE: To develop a quality assessment tool for care rendered to enrollees in
      the Program for All-inclusive Care of the Elderly (PACE) that can discriminate
      care quality ratings across PACE sites. DESIGN: Structured implicit review (SIR)
      of medical records by trained geriatricians and geriatric nurse practitioners.
      SETTING: Eight PACE sites. PARTICIPANTS: Older adults enrolled in a PACE program
      for at least 6 months (n = 313). MEASUREMENTS: Process and outcome measures for
      both overall care and 14 specific conditions (tracers) managed up to 1 year.
      RESULTS: Overall care quality was judged to be above a community standard in 56%
      and below standard in 8% of cases. Process of care was rated as very good or good
      in 70% of the cases. Outcomes depended on how questions were phrased: only 19% of
      cases improved, whereas 28% were judged to have fared better than expected given
      their condition at baseline. The SIR method produced ratings demonstrating
      considerable variability across the sites; three of the sites consistently showed
      poorer quality ratings than the other five. CONCLUSIONS: PACE care was generally
      assessed to be of good quality, but with room for improvement. Despite
      significant limitations of poor interrater reliability for process of care
      measures, excessive time involved for the reviews, and lack of a control group,
      the SIR method was able to consistently discriminate quality ratings among PACE
      sites. A modified version of the assessment instrument could prove useful in a
      quality improvement program for PACE care.

PMID- 10968294
TI  - Consistency of physicians' legal standard and personal judgments of competency in
      patients with Alzheimer's disease.
AB  - OBJECTIVES: To investigate the consistency of physician judgments of treatment
      consent capacity (competency) for patients with Alzheimer's disease (AD) when
      specific legal standards (LS) for competency are used, and to identify the LS
      most clinically relevant to experienced physicians. DESIGN: Control and AD
      patient participants were videotaped being administered a measure of capacity to
      consent to medical treatment. Study physicians viewed videotapes of these
      assessments individually and made competency judgments for each participant under
      different LS followed by their own personal judgment of competency. SETTING: A
      university medical center. PARTICIPANTS: Participants were 10 older controls and
      21 patients with AD (10 with mild and 11 with moderate AD). Five physicians with
      experience assessing the competency of AD patients were recruited from the
      geriatric psychiatry, geriatric medicine, and neurology services of a university
      medical center. MEASUREMENTS: The 31 participants were videotaped performing on a
      measure of treatment consent capacity (Capacity to Consent to Treatment
      Instrument) (CCTI). The CCTI consists of two clinical vignettes (A-neoplasm and B
      cardiac) that test competency under five LS. Vignette A and B assessments were
      videotaped separately for each participant (total videotapes for sample = 62).
      Each study physician viewed each videotaped vignette individually, made judgments
      under each of the LS (competent or incompetent), and then made his/her own
      personal competency judgment. Physicians were blinded to participant diagnosis.
      Within participant group, consistency of physician judgments was evaluated across
      LS and personal judgments using percentage agreement and kappa. Agreement between
      personal and LS judgments for the AD group was evaluated for each physician using
      logistic regression. RESULTS: As expected, physicians as a group generally
      demonstrated very high percentage agreement in their LS and personal competency
      judgments for the control group. For the AD group, mean percentage judgment
      agreement among physicians ranged from a high of 84% (LS1) (evidencing a
      treatment choice) to a low of 67% (LS3) (appreciating consequences of treatment
      choice). Mean percentage agreement for personal competency judgments was 76%. For
      the AD sample, kappa analyses for physicians as a group demonstrated significant
      agreement not attributable to chance for LS5 (understanding treatment
      situation/choices) (k = 0.57, P = .001), LS4 (providing rational reasons for
      treatment choice) (k = 0.39, P = .04), and also for personal judgments (k = 0.48,
      P = .009). Analysis of LS judgment agreement within physician indicated that
      physicians applied the LS as discrete standards. Within-physician and for the AD
      sample, personal competency judgments were associated significantly with
      judgments on LS5 (P = .001), LS4 (P = .004), and LS3 (P < .04). CONCLUSIONS:
      Experienced physicians demonstrated significant agreement assessing competency in
      AD patients when judgments were based upon specific legal standards. Personal
      competency judgments of physicians showed a substantially higher level of
      agreement than found in a previous study, where specific LS were not used. These
      results suggest that consistency of physician competency judgments can be
      enhanced if they are guided by knowledge of specific LS. Physicians' personal
      competency judgments were most closely associated with comprehension and
      reasoning LS, the most conservative and clinically appropriate standards for
      deciding competency.

PMID- 10968295
TI  - Cognitive models of physicians' legal standard and personal judgments of
      competency in patients with Alzheimer's disease.
AB  - OBJECTIVES: To investigate measures of patient cognitive abilities as predictors
      of physician judgments of medical treatment consent capacity (competency) in
      patients with Alzheimer's disease (AD). DESIGN: Predictor models of legal
      standards (LS) and personal competency judgments were developed for each study
      physician using independent neuropsychological test measures and logistic
      regression analyses. SETTING: A university medical center. PARTICIPANTS: Five
      physicians with experience assessing the competency of AD patients were recruited
      to make competency judgments of videotaped vignettes from 10 older controls and
      21 patients with AD (10 with mild and 11 with moderate dementia). MEASUREMENTS:
      The 31 patient and control videotapes of performance on a measure of treatment
      consent capacity (Capacity to Consent to Treatment Instrument) (CCTI) were rated
      by the five physicians. The CCTI consists of two clinical vignettes (A-neoplasm
      and B-cardiac) that test competency under five LS. Each study physician viewed
      each vignette videotape individually, made judgments of competent or incompetent
      under each of the LS, and then made his/her own personal competency judgment.
      Physicians were blinded to participant diagnosis and neuropsychological test
      performance. Stepwise logistic regression was conducted to identify cognitive
      predictors of each physician's LS and personal competency judgments for Vignette
      A using the full sample (n = 31). Classification logistic regression analysis was
      used to determine how well these cognitive predictor models classified each
      physician's competency judgments for Vignette A. These classification models were
      then cross-validated using physician's Vignette B judgments. RESULTS: Cognitive
      predictor models for Vignette A competency judgments differed across individual
      physicians, and were related to difficulty of LS and to incompetency outcome
      rates across LS for AD patients. Measures of semantic knowledge and receptive
      language predicted judgments under less difficult LS of evidencing a treatment
      choice (LS1) and making the reasonable treatment choice (LS2). Measures of
      semantic knowledge, short-term verbal recall, and simple reasoning ability
      predicted judgments under more difficult and clinically relevant LS of
      appreciating consequences of a treatment choice (LS3), providing rational reasons
      for a treatment choice (LS4), and understanding the treatment situation and
      choices (LSS). Cognitive models for physicians' personal competency judgments
      were virtually identical to their respective models for LS5 judgments. For AD
      patients, shortterm memory predictors were associated with high incompetency
      outcome rates (over 70%), a simple reasoning measure was associated with
      moderately high incompetency outcome rates (60-70%), and a semantic knowledge
      measure was associated with lower incompetency outcome rates (30-60%). Overall,
      single predictor models were relatively robust, correctly classifying an average
      of 83% of physician judgments for Vignette A and 80% of judgments for Vignette B.
      CONCLUSIONS: Multiple cognitive functions predicted physicians' LS and personal
      competency judgments. Declines in semantic knowledge, short-term verbal recall,
      and simple reasoning ability predicted physicians' judgments on the three most
      difficult and clinically most relevant LS (LS3-LS5), as well as their personal
      competency judgments. Our findings suggest that clinical assessment of competency
      should include evaluation of semantic knowledge, verbal recall, and simple
      reasoning abilities.

PMID- 10968296
TI  - Driving cessation in older men with incident dementia.
AB  - OBJECTIVE: To determine the prevalence and cessation of driving among older men
      with incident dementia in the Honolulu-Asia Aging Study. DESIGN: Retrospective
      cohort data from a community-based study of incident dementia. SETTING: The
      Honolulu Heart Program and the Honolulu-Asia Aging Study. PARTICIPANTS: A total
      of 643 men who were evaluated for the incidence of Alzheimer's disease or other
      dementia between the fourth and the fifth examination of the Honolulu Heart
      Program. MEASUREMENTS: Driving history, diagnosis of dementia, grip strength,
      walking speed, standing balance test, interviewer's rating of vision status, and
      the neurologist's notes on mentions of driving behavior from informal interviews
      with a caregiver or family informant. RESULTS: The prevalence of driving declined
      dramatically with level of cognitive functioning. Among 162 men evaluated and
      found to have normal cognitive functioning, 78% still drove, compared with 62% of
      287 men with poor cognitive functioning but no clinical dementia, 46% of 96 men
      with a new diagnosis of very mild dementia (Clinical Dementia Rating = 0.5), and
      22% of 98 men with a new diagnosis of mild dementia (CDR = 1). Only one of 23 men
      diagnosed with moderate or more severe staged incident dementia (CDR > 1) was
      driving. About 10% of the 59 demented persons still driving relied on co-pilots,
      and only one driver was reported as involved in a crash according to a review of
      the neurologists' notes. CONCLUSIONS: Incident dementia is a major cause of
      driving cessation. Based on these data, we estimate that approximately 4% of male
      drivers aged 75 years and older nationwide (about 175,000 men) have dementia.
      This number will increase with the projected growth of drivers aged 75 years and
      older.

PMID- 10968298
TI  - Predictors of nursing home placement in Parkinson's disease: a population-based,
      prospective study.
AB  - OBJECTIVES: To examine the rate and predictors of nursing home placement in
      patients with Parkinson's disease. DESIGN: Four-year prospective study. SETTING:
      A population-based study in western Norway PARTICIPANTS: 178 community-dwelling
      subjects with Parkinson's disease. MEASUREMENTS: Main outcome measure was the
      time from baseline to nursing home admission. Baseline evaluation of motor
      symptoms (Unified Parkinson's Disease Rating Scale, UPDRS), cognition (clinical
      dementia interview, Gottfries, Brane & Steen dementia scale, and Mini-Mental
      State Examination), depression (clinical interview and the Montgomery & Asberg
      Depression Rating Scale), and psychotic symptoms (UPDRS Thought Disorder item)
      were performed. RESULTS: Forty-seven patients (26.4%) were admitted to a nursing
      home during the 4-year study period. Institutionalized patients were older, had
      more advanced Parkinson's disease with more severe motor symptoms and impairment
      of activities of daily living, were cognitively more impaired, were more often
      living alone, and had more hallucinations than those who continued to live at
      home. Duration of disease, levodopa dose, and gender distribution did not differ
      between the two groups. A Cox proportional hazards linear regression analysis
      showed that old age, functional impairment, dementia, and hallucinations were
      independent predictors of nursing home admission. CONCLUSIONS: Both motor and
      neuropsychiatric symptoms contributed to institutionalization, but the presence
      of hallucinations was the strongest predictor. This finding indicates it is
      possible that effective treatment of hallucinations may reduce the need for
      institutionalization in patients with Parkinson's disease.

PMID- 10968297
TI  - The impact of legislation on psychotropic drug use in nursing homes: a cross
      national perspective.
AB  - OBJECTIVES: To quantify the impact of legislation on nursing home residents,
      psychotropic drug use, and the occurrence of falls in the US compared with five
      countries with no such regulation. DESIGN: A retrospective cross-sectional study
      SETTING: Nursing homes in five US states and selected nursing homes in Denmark,
      Iceland, Italy, Japan, and Sweden. PARTICIPANTS: Residents in nursing homes in
      five US states and the aforementioned countries during 1993-1996. MAIN OUTCOME
      MEASURES: Using data collected using the Minimum Data Set, logistic regression
      provided estimates of the legislative effects on the use of antipsychotics and
      antianxiety/hypnotics while simultaneously adjusting for potential confounders.
      The occurrence of falls was evaluated similarly. RESULTS: Prevalence of
      antipsychotic and/or antianxiety/ hypnotic use varied substantially across
      countries. After adjustment for differences in age, gender, presence of
      psychiatric/neurologic conditions, and physical and cognitive functioning,
      residents in Denmark, Italy, and Sweden were at least twice as likely to receive
      these drugs (Denmark Odds Ratio (OR)=2.32; 95% Confidence Intervals (CI), 2.15
      2.51; Italy OR=2.05; 95% CI, 1.78-2.34; Sweden OR=2.50; 95% CI, 2.16-2.90); in
      Iceland, the risk was increased to greater than 6 times (OR=6.54; 95% CI, 5.75
      7.44) that of the US. Residents were less likely to fall in Italy, Iceland, and
      Japan compared with the US, despite more extensive use of psychotropic
      medication, whereas residents in Sweden and Denmark were more likely to fall.
      CONCLUSIONS: Policy has had an impact on the prescribing of psychotropic
      medication in US nursing homes compared with other countries, but it is unclear
      if this is translated into better outcomes for residents.

PMID- 10968299
TI  - Prevalence, effectiveness, and predictors of planning the place of death among
      older persons followed in community-based long term care.
AB  - BACKGROUND: Little is known about whether patients plan for the site of their
      death and whether such planning is effective. OBJECTIVE: To determine the
      prevalence, effectiveness, and predictors of planning the place of death among
      older homebound persons followed in a community-based, physician-led house call
      program. DESIGN: Retrospective chart review. SETTING: A geographically defined
      catchment area in southeast Baltimore, Maryland. PATIENTS: One hundred twenty
      five patients who died between July 1995 and November 1998 who were followed in a
      physician-led house call program. MAIN OUTCOME MEASURES: Presence of a plan to
      die in a specific place and concordance between planned and actual place of
      death. RESULTS: Eighty patients (64%) made a plan to die in a specific place, and
      these plans were executed successfully in 73 cases (91%). The median time between
      formulating a plan to die in a specific place and death was 36 days. In logistic
      regression analysis, making a plan to die in a specific place was positively
      associated with an advance directive of Do Not Resuscitate (DNR) (odds ratio (OR)
      11.7, confidence interval (CI) 3.7, 32.5) and negatively associated with the lack
      of an identifiable main medical problem other than being homebound (OR 0.17; CI,
      0.02-0.88). CONCLUSIONS: Among a group of frail older persons living in the
      community, planning to die in a particular place was common and implemented
      successfully most of the time. Providing physician care at home may facilitate
      improved end-of-life care for older persons.

PMID- 10968300
TI  - Immunologic response to a single dose of tetanus toxoid in older people.
AB  - OBJECTIVES: Several studies have demonstrated that a large percentage of older
      people are inadequately immunized against tetanus. The aim of this study was to
      assess the immunity against tetanus in a group of individuals aged 69 and older
      and to examine the immune response to a single dose of tetanus toxoid. DESIGN: A
      convenience sample of 115 residents of a large retirement home, aged 69 and
      older, was studied. After a blood sample for anti-tetanus antibody titer, a
      single dose of tetanus toxoid vaccine was administered. Repeat titers were
      obtained 6 weeks after the vaccination and analyzed by ELISA assay. Antibody
      levels equal to or greater than 0.1 IU/mL were considered protective. RESULTS:
      Sixty-seven of 115 (58.3%) individuals had adequate antibody titers. Those
      individuals who reported having been vaccinated with tetanus toxoid in the past
      were more likely to be immunized adequately compared with those who reported
      having never been vaccinated (66.7% vs 39.3%, P = .02). After vaccination, 34 of
      46 (73.9%) individuals with inadequate antibody titers became seropositive. Those
      who remained seronegative had mean prevaccination antibody titers significantly
      lower than those who seroconverted. Sixteen of 17 (94.1%) persons who reported
      having been vaccinated in the past and were found to be seronegative developed
      adequate antibody titers following vaccination, compared with only nine of 16
      (56.2%) who reported never having been vaccinated (P = .04). There was no
      association between seroconversion rate and age, sex, underlying diseases, and
      army service. CONCLUSIONS: Most individuals will develop an adequate anti-tetanus
      antibody titer following administration of a single dose of tetanus vaccine. A
      history of past immunization is a good predictor of becoming adequately
      immunized. It is important that physicians follow the current recommendations for
      adult immunization and initiate campaigns to ensure that the older population is
      protected against tetanus.

PMID- 10968301
TI  - Attrition in an exercise intervention: a comparison of early and later dropouts.
AB  - OBJECTIVE: To identify reasons for dropout and factors that may predict dropout
      from an exercise intervention aimed at improving physical function in frail older
      persons. DESIGN/SETTING: An 18-month randomized controlled intervention in a
      community setting. The intervention comprised 2 groups: class-based and self
      paced exercise. PARTICIPANTS: 155 community-dwelling older persons, mean age
      77.4, with mildly to moderately compromised mobility. MEASUREMENTS: The primary
      outcome measure was dropout. Dropouts were grouped as: D0, dropout between
      baseline and 3-month assessment, and D3, dropout after 3-month assessment.
      MEASUREMENTS: Measurements of demographics, health, and physical performance
      included self-rated health, SF-36, disease burden, adverse events, PPT-8,
      MacArthur battery, 6-minute walk, and gait velocity. RESULTS: There were 56
      dropouts (36%), 31 in first 3 months. Compared with retained subjects (R), the D0
      group had greater disease burden (P = .011), worse self-perceived physical health
      (P = .014), slower usual gait speed (P = .001), and walked a shorter distance
      over 6 minutes (P<.001). No differences were found between R and D3. Multinomial
      logistic regression showed 6-minute walk (P<.001) and usual gait velocity
      (P<.001) were the strongest independent predictors of dropout. Controlling for
      all other variables, adverse events after randomization and 6-minute walk
      distance were the strongest independent predictors of dropout, and self-paced
      exercise assignment increased the risk of dropout. CONCLUSIONS: We observed
      baseline differences between early dropouts and retained subjects in disease
      burden, physical function, and endurance, suggesting that these factors at
      baseline may predict dropout. Improved understanding of factors that lead to and
      predict dropout could allow researchers to identify subjects at risk of dropout
      before randomization. Assigning targeted retention techniques in accordance with
      these factors could result in decreased attrition in future studies. Therefore,
      the results of selective attrition of frailer subjects, such as decreased
      heterogeneity, restricted generalizability of study findings, and limited
      understanding of exercise effects in this population, would be avoided.

PMID- 10968302
TI  - Breast cancer screening for older women in a primary care practice.
AB  - OBJECTIVE: To determine rates of breast cancer screening for older women cared
      for in a primary care practice and to identify associations between patient and
      physician characteristics and breast cancer screening. STUDY DESIGN: A
      retrospective cohort study of older women. SETTING: An urban hospital-based
      academic general medicine practice. This practice uses a computerized medical
      record and office procedures that facilitate tracking and ordering of mammograms.
      PARTICIPANTS: A random sample of 130 women aged 65 to 80 who receive primary care
      at a hospital-based general medicine practice. MEASUREMENTS: Data were collected
      from the hospital's computerized medical record. We recorded all clinical breast
      exams and mammograms performed or recommended during the 2-year study period.
      RESULTS: The median age of the 130 women studied was 71, and 21% of the women
      were black. Most patients had no serious comorbid illness (69%) and were
      independent in their activities of daily living (92%). During the 2-year study
      period, mammography was recommended for 95% of women and completed for 84%, and
      clinical breast exam was performed on 75%. Patients of male physicians had higher
      rates of mammography than patients of female physicians (89% vs. 75%, P = .045).
      Patients of faculty physicians had higher rates of clinical breast exam than
      patients of house officers or fellows (83% vs. 56%, P = .001). CONCLUSIONS: We
      report a very high rate of mammography for women cared for at a hospital-based
      primary care practice. The systems in place to facilitate ordering and tracking
      of mammograms probably contributed to the unusually high rate of mammography
      observed.

PMID- 10968304
TI  - Mitral balloon valvotomy for the treatment of mitral stenosis in octogenarians.
AB  - OBJECTIVES: To study the safety and benefit of mitral balloon valvotomy (MBV) in
      patients aged > or =80 years. SETTING: A tertiary cardiac centre DESIGN: A
      retrospective study of 20 octogenarians (mean age 83, range 80-89 years) in whom
      percutaneous MBV was performed as a definitive or palliative treatment for severe
      mitral stenosis. All were in New York Heart Association (NYHA) symptom class III
      or IV. Fourteen had been judged unfit for cardiac surgery. Hemodynamic data was
      recorded before and after MBV. Symptomatic outcome was documented at 1 month for
      all patients. Outcome at 1 year was available for 16 patients. RESULTS:
      Dilatation of the mitral valve was achieved in all patients without major
      complications. Mean mitral valve area increased 106% from 0.81 (+/-0.3) to 1.67
      (+/- 0.8) cm2, transvalvular gradient decreased from 11.8 (+/- 4.8) to 5.6 (+/
      2.9) mm Hg, cardiac output increased from 3.1 (+/- 0.6) to 4.1 (+/- 1.4) l/min
      (all P<.01). Eight of these 20 patients obtained a valve area > or =1.5 cm2, and
      16 obtained an area > or = 1.2 cm2. One month after BMV, all patients were alive,
      and 16 of the 20 patients were improved by at least one NYHA class. This
      improvement was sustained in 7 of 16 patients followed up for 1 year. More severe
      mitral valve degenerative change, determined by echocardiography, was associated
      with poorer outcome. CONCLUSIONS: In this group of very old and frail patients,
      MBV was safe and resulted in significant immediate improvement. Sustained
      symptomatic benefit at 1 year was obtained in those with less extensive leaflet
      and subvalvular disease. In patients with severe degenerative valve disease on
      echocardiography, but unacceptable surgical risk, MBV offers short-term
      palliation.

PMID- 10968305
TI  - Agreement between older subjects and proxy informants on history of surgery and
      childbirth.
AB  - OBJECTIVES: To assess the agreement between proxy informants' reports of history
      of surgery and childbirth and older index subjects' own recall. DESIGN:
      Interrater reliability study. SETTING: An outpatient family medicine clinic and a
      provincial electoral district in Montreal, Canada. PARTICIPANTS: Eighty-two
      subjects aged 65 years and older without cognitive impairment, identified from
      clinic and community settings, and each index subject's proxy respondent.
      MEASUREMENTS: Identical questionnaires were administered to index subjects and
      proxies. RESULTS: Proxies failed to report 39% of non-childbirth surgeries
      reported by index subjects, but failed to report only 10% of childbirths. Female
      proxies were significantly less likely than male proxies to underreport non
      childbirth surgeries after controlling for age of index subject and interval
      since surgery. Longer interval since surgery was significantly associated with
      greater underreporting, whereas age of the index subject and relationship between
      proxy and index subject were not. Agreement between proxies and index subjects on
      date of surgery was much higher for childbirths than for non-childbirth
      surgeries. CONCLUSIONS: Our findings suggest that proxy respondents can provide
      reliable information on older women's history of childbirth but that use of proxy
      respondents for history of non-childbirth surgeries may result in substantial
      underreporting.

PMID- 10968306
TI  - Country profile: Israel.

PMID- 10968303
TI  - A population-based study on motor performance and white matter lesions in older
      women.
AB  - OBJECTIVE: To investigate the relationship between motor performance and white
      matter lesions (WMLs) on computed tomography (CT) of the brain in older women.
      DESIGN: Cross-sectional study. SETTING: Population-based study in Goteborg,
      Sweden. PARTICIPANTS: A total of 248 women aged 70, 74, and 78 years.
      MEASUREMENTS: Motor performance was measured by a Postural-Locomotion-Manual
      (PLM) test using an optoelectronic technique. WMLs on CT scans were rated as no,
      mild, moderate, or severe. RESULTS: White matter lesions were associated with
      impaired mobility of the lower extremities, that is, prolonged locomotion phase
      in the PLM test. This association was also present after controlling for age,
      hypertension, coronary heart disease, stroke, diabetes mellitus, chronic
      bronchitis, intermittent claudication, and smoking. CONCLUSIONS: Cerebral white
      matter lesions may contribute to motor impairments in older adults.

PMID- 10968307
TI  - Substance abuse in older people.

PMID- 10968308
TI  - The effect of case management on the costs of health care for enrollees in
      Medicare Plus Choice plans: a randomized trial.
AB  - OBJECTIVE: To measure the effects of case management on an older population's
      costs of health care. DESIGN: A 1-year randomized controlled trial. SETTING:
      Multiple sites of care in San Francisco, California. PARTICIPANTS: Patients aged
      65 or older of primary care physicians in a large provider organization bearing
      financial risk for their care (n = 6409). INTERVENTION: Screening for high risk
      and provision of social work-based case management. OUTCOME MEASURES: Volume and
      cost of hospital, physician, case management, and other health-related services.
      RESULTS: The experimental group used more case management services than the
      control group (0.09 vs. 0.02 months per person, P<.001). The experimental group's
      average total payments for health care were slightly lower ($3148 vs $3277, P =
      .40). CONCLUSIONS: This study provides no statistically significant evidence that
      social work-oriented case management reduces the use or the cost of health care
      for high-risk older people. Other potentially favorable effects of this type of
      case management need to be evaluated, as do the effects of other types of case
      management.

PMID- 10968309
TI  - Long-term home health care for the impoverished frail homebound aged: a twenty
      seven-year experience.

PMID- 10968310
TI  - Removing the barriers to effective depression treatment in old age.

PMID- 10968311
TI  - Why physicians need to become more proficient in assessing their patients'
      competency and how they can achieve this.

PMID- 10968312
TI  - After aging.

PMID- 10968313
TI  - The challenge of measuring quality of care in PACE. Program of All Inclusive Care
      for the Elderly.

PMID- 10968314
TI  - Encouraging physical fitness for older people.

PMID- 10968315
TI  - Oral therapy for cobalamin deficiency.

PMID- 10968316
TI  - Pyogenic liver abscess: a geriatric problem.

PMID- 10968317
TI  - Comparison of rectal and infrared ear temperatures in older hospital inpatients.

PMID- 10968318
TI  - Change in functional status during hospitalization in older adults: a geriatric
      concept of frailty.

PMID- 10968319
TI  - Clinical impact of an infectious disease service on the management of bloodstream
      infection.
AB  - The impact of an infectious disease (ID) service on the optimal antibiotic
      management of 103 patients with bloodstream infections, defined as bacteremia and
      systemic inflammatory response syndrome, was evaluated. The optimal antibiotic
      management was defined according to the Sanford Guide to Antimicrobial Therapy
      (1996) or written internal guidelines. The judgment on optimal antibiotic
      management was made at the time of reporting the positive blood culture results.
      Switching from a broad-spectrum to a narrow-spectrum agent was carried out
      significantly more often by the ID service than by the attending physicians (25
      of 25 vs. 20 of 40; P<0.001). In patients without empirical therapy, the ID
      service initiated optimal antimicrobial therapy significantly more often than
      physicians without training in infectious diseases (12 of 12 vs. 4 of 10,
      P=0.0028). Three of 12 patients in whom the attending physician misinterpreted
      the positive blood culture result needed 8 days to 4 months of additional
      hospitalization. In summary, patients for whom an ID service was provided
      received appropriate treatment more often and experienced significantly fewer
      complications.

PMID- 10968320
TI  - Clinical and microbiological characteristics of bacteremia caused by
      Acinetobacter lwoffii.
AB  - A retrospective study was conducted to analyze the clinical features and
      pathogenic roles of bacteremia caused by Acinetobacter lwoffii during a 4-year
      period. Acinetobacter lwoffii (formerly Acinetobacter calcoaceticus var. lwoffii)
      is recognized as normal flora of the skin, oropharynx and perineum of healthy
      individuals. There are few reports of Acinetobacter lwoffii bacteremia associated
      with indwelling catheters in humans, particularly in immunocompromised hosts. The
      records of 18 patients with Acinetobacter lwoffii bacteremia whose underlying
      conditions included cancer (11 patients), systemic lupus erythematosus (n=1),
      chronic obstructive pulmonary disease (n = 2) and other diseases (n = 4), all but
      one of whom had indwelling catheters during the bacteremic episode, were
      examined. The clinical syndromes were classified as probable catheter-related
      bacteremia (n = 14), definite catheter-related bacteremia (n = 2), primary
      bacteremia (n = 1) or biliary tract infection (n = 1). The infections improved
      after removal of the catheter and/or appropriate antimicrobial therapy. One death
      was attributable to the bacteremic event. The results of this study show that
      indwelling catheter-related Acinetobacter lwoffii bacteremia in immunocompromised
      hosts appears to be associated with a low risk of mortality.

PMID- 10968322
TI  - Strain characterization of Candida parapsilosis fungemia by molecular typing
      methods.
AB  - The present study used two molecular typing methods to investigate a cluster of
      eight cases of Candida parapsilosis fungemia in a hospital in Rio de Janeiro,
      Brazil. Candida parapsilosis is an important opportunistic pathogen that is
      frequently involved in outbreaks of nosocomial fungemia. Identification of a
      common source of infection and determination of genetic relatedness among the
      strains involved in outbreaks are important for infection control. Candida
      parapsilosis strains were isolated from the bloodstream of patients housed in an
      intensive-care unit (n=5) and in individual rooms (n=3). An additional strain of
      Candida parapsilosis was isolated from a hyperalimentation infusion flask, which
      was implicated by molecular typing to be the source of infection. All strains
      were identified using morphological and biochemical methods. The genetic
      relationship between patients' strains and the hyperalimentation infusion strain
      was assessed by electrophoretic karyotype (EK) analysis and random amplification
      of polymorphic DNA (RAPD). Both methods resulted in patterns that allowed
      differentiation of the isolates. Candida parapsilosis fungemia, in three of the
      eight patients, resulted from a common source of infection, as demonstrated by
      molecular typing methods. Image analysis of EK patterns indicated that these
      strains were closest to Candida parapsilosis Group II, a grouping that is a less
      frequent clinical isolate than the major Group I strains.

PMID- 10968321
TI  - Effect on diphtheria immunity of combined tetanus and diphtheria booster
      vaccination in adults.
AB  - The effect of a single booster injection of an adult formulation of a combined
      diphtheria-tetanus vaccine (Td) on diphtheria-specific immunity was evaluated.
      The booster injection, containing 2 IU diphtheria toxoid per dose, was given as
      part of the surgical wound management for adults with open soft tissue injuries.
      Diphtheria antitoxin concentrations were determined in serum samples from 534
      patients (199 women and 335 men, aged 18-70 years) using an enzyme immunoassay
      and a tissue culture toxin neutralization assay. Seroimmunity against diphtheria
      toxin was classified at three levels: susceptibility, basic protection, and full
      protection against the toxic manifestations of the disease. Before vaccination,
      27.1% of the subjects were susceptible to diphtheria, 26.5% had basic protection,
      and 46.4% were fully protected. Six weeks (minimum 25 days, maximum 98 days)
      after a single booster injection, 89.7% of the subjects achieved full protection
      against diphtheria, and only 3.9% had antitoxin levels below the protective
      level. The median increase from the prevaccination to postvaccination antitoxin
      concentration was found to be 14-fold (4.4-47; quartiles Q25 to Q75). The change
      in antitoxin levels after revaccination was higher in older age groups (P<
      0.001), whereas neither sex (P = 0.86) nor the country of previous immunization
      with a different national immunization schedule (P=0.61) had a significant
      influence on the revaccination effect. Systemic adverse reactions were rare, and
      local reactions of clinical significance were reported in only 1.9% of subjects.

PMID- 10968323
TI  - Intrathecal synthesis of specific antibodies in patients with invasion of the
      central nervous system by Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae commonly causes respiratory tract infections in humans, but
      it may also be associated with central nervous system manifestations. The aim of
      the present study was to determine whether the cerebrospinal fluid taken from
      patients with neurologic symptoms due to Mycoplasma pneumoniae infection contains
      specific antibodies and whether the detection of these antibodies can be used for
      diagnosis. Mycoplasma pneumoniae was isolated from the cerebrospinal fluid taken
      from nine patients with central nervous system symptoms on admission to the
      hospital. In addition, Mycoplasma pneumoniae was detected in cerebrospinal fluid
      using polymerase chain reaction in four other patients. Antibodies to Mycoplasma
      pneumoniae were detected using the enzyme immunosorbent assay, indirect
      immunoperoxidase assay and immunoblotting in cerebrospinal fluid samples from 14
      of 19 patients included in the study. The indirect immunoperoxidase assay showed
      high titers of Mycoplasma pneumoniae immunoglobulin G1 (IgG1) and IgM antibodies
      in cerebrospinal fluid samples of some patients with meningoencephalitis or
      meningitis. Titers of specific IgA, IgG2 and IgG3 antibodies were lower, while
      specific IgG4 was not detectable. Cerebrospinal fluid samples with higher
      antibody titers also contained IgA, IgG1, IgG2, IgG3 and IgM antibodies that
      recognized the P1 adhesin (170 kDa protein) of Mycoplasma pneumoniae. A
      comparison of antibody titers of concomitant serum/cerebrospinal fluid samples to
      Mycoplasma pneumoniae and those to measles virus by enzyme immunosorbent assay
      suggested the intrathecal synthesis of IgG and IgM antibodies to Mycoplasma
      pneumoniae in patients with acute meningoencephalitis. Data from this study
      clearly reinforce previous findings that Mycoplasma pneumoniae is an etiologic
      agent of central nervous system infections in humans.

PMID- 10968324
TI  - Nosocomial spread of hepatitis B virus in two hemodialysis units, investigated by
      restriction fragment length polymorphism analysis.
AB  - A method for genotyping hepatitis B virus (HBV) strains, based on restriction
      fragment length polymorphism (RFLP) analysis of four different amplified
      fragments of the HBV genome, was used to investigate nosocomial infections that
      occurred in two Brazilian hemodialysis centers. Viral isolates from hepatitis B
      surface antigen (HBsAg)-positive serum samples from 27 hemodialysis patients and
      39 HBV-positive unrelated control patients were grouped according to their RFLP
      patterns. Strains isolated from the control patients were divided into nine RFLP
      patterns: A1, A2, A3 (genotype A), D1, D2, D3, D4 (genotype D), F1, and F2
      (genotype F). In hemodialysis unit A (Rio de Janeiro), 14 HBV isolates were
      grouped into five different RFLP patterns: A1, A2, A3, D3, and D4. Pattern A2,
      present at a relatively low prevalence (18%) in the control group, was observed
      in the majority (53%) of the hemodialysis patients. Notably, all five patients
      who seroconverted to HBsAg positivity in 1995 carried the strain A2. In
      hemodialysis unit B (state of Sao Paulo), where an outbreak of HBV infection
      occurred in 1996-1997, RFLP analysis showed that all 13 patients who
      seroconverted were infected with HBV isolates of genotype D. Coinfection with
      strain A1 was detected in seven of them. The results demonstrate the value of
      RFLP analysis in establishing common sources of infection in hemodialysis
      centers.

PMID- 10968325
TI  - Secondary resistance among 554 isolates of Helicobacter pylori after failure of
      therapy.
AB  - In a study to determine secondary resistance among Helicobacter pylori isolates,
      gastroenterologists from several German cities submitted over a 3-year period to
      centre A (Regensburg) or centre B (Freiburg) gastric biopsies from patients in
      whom one or more therapies to eradicate Helicobacter pylori had failed. Rates of
      resistance among the collections of 302 (centre A) and 252 (centre B) isolates
      were, respectively, as follows: to metronidazole, 75% and 66%; to clarithromycin,
      58% and 49%; to amoxicillin, 0%; to ciprofloxacin, 9%; to doxycycline, 0%; and to
      rifampin, 0%. Resistance to clarithromycin was associated with metronidazole
      resistance in 89% and 85% of the isolates in centre A and centre B, respectively.

PMID- 10968326
TI  - Outbreak of Campylobacter infection in a subartic community.
AB  - A presumably waterborne outbreak of Campylobacter jejuni/coli infection in a
      subarctic community is described. Drinking water supplied to residents was
      delivered unchlorinated during a 4-week period. No Campylobacter sp. was
      recovered from the water supply. Three hundred thirty individuals (15% of the
      2,200 exposed) became ill. Diarrhoea, abdominal pain, fever, nausea and joint
      pain occurred in 81%, 30%, 29%, 43% and 21%, respectively. Nine percent reported
      swelling of joints, and two cases of reactive arthritis occurred. A Campylobacter
      sp. was isolated from 9 of 33 individuals who became ill and from 1 of 33 healthy
      controls. All culture-positive individuals, 46% of culture-negative ill persons
      and 27% of healthy controls were seropositive. All strains recovered had an
      identical DNA profile.

PMID- 10968327
TI  - Astrovirus infection among children with gastroenteritis in the city of Zaragoza,
      Spain.
AB  - The incidence of astrovirus infection in children less than 10 years of age with
      gastroenteritis in the city of Zaragoza, Spain, was analysed during a 12-month
      period. A total of 718 stool samples obtained from 534 children were examined. In
      401 samples no routinely searched for pathogenic organism was detected; these
      specimens were then tested for the presence of astrovirus antigens. Astrovirus
      was detected in the samples of 15 (5.5%) patients, a detection rate similar to
      that recognised for Yersinia enterocolitica and Cryptosporidium spp. All children
      with confirmed astrovirus infection had diarrhoea (median duration, 9 days), 11
      experienced loss of appetite, 5 vomiting, and 4 fever. The incidence of
      astrovirus infection reported here indicates that Spanish children suffering from
      gastroenteritis should be routinely screened for the presence of astrovirus.

PMID- 10968328
TI  - Impact of moxifloxacin versus clarithromycin on normal oropharyngeal microflora.
AB  - A multiple-dose, randomized, double-blind, controlled, cross-over trial was
      performed in 12 healthy male subjects in order to investigate the effect of a 7
      day treatment with moxifloxacin (400 mg orally, once daily) versus clarithromycin
      (500 mg orally, twice daily) on the normal oropharyngeal microflora. Moxifloxacin
      caused significant reductions in levels of alpha-streptococci and Neisseria cocci
      during the treatment period, while the numbers of gram-negative anaerobic
      bacteria increased markedly during moxifloxacin administration. Clarithromycin
      administration caused a suppression of micrococci and corynebacteria, while no
      significant changes were recorded in the anaerobic microflora. No new colonizing
      moxifloxacin-resistant strains were isolated during the investigation period.

PMID- 10968329
TI  - Evaluation of ceftazidime concentration released in agar from an E test strip.
AB  - The aim of this study was to evaluate, using high-performance liquid
      chromatography, the concentration of ceftazidime in agar released from an E test
      strip, sampling at the edge of the strip at different points (1, 2, 4, 8, 16, 32,
      64, and 128 microg/ml) at 6, 15, and 24 h after its deposition on uninoculated
      plates. From 6 to 24 h, the ceftazidime concentration in agar increased at the
      graduations 1, 2, and 4 microg/ml (+140, +82, and +58%, respectively), remained
      fairly constant at 8 microg/ml (-1.9%), and decreased at 16, 32, 64, and 128
      microg/ml (-25, -44, -36, and -58%, respectively). In the 6-24 h range, the
      ceftazidime concentrations between 16 and 1 microg/ml were +/-1 serial dilution
      of the values reported on the strip, confirming the accuracy of the E test in
      agar.

PMID- 10968330
TI  - Influence of rheumatoid factor on the specificity of a rapid
      immunochromatographic test for diagnosing dengue infection.
AB  - In order to determine the influence of rheumatoid factor in serum specimens on
      the specificity of an immunochromatographic test for the detection of antibodies
      against dengue virus, 50 clinical specimens containing rheumatoid factor were
      evaluated for cross reactivity with a commercially available assay. While
      specificity for the detection of immunoglobulin (Ig) G antibodies was 100%, the
      IgM component of the test showed false-positive results in 26% of cases. Thus, it
      is important to consider interference by rheumatoid factor when using
      immunochromatographic assays for the detection of specific IgM produced during
      dengue infection.

PMID- 10968331
TI  - False-positive IgM antibody tests for cytomegalovirus in patients with acute
      Epstein-Barr virus infection.
AB  - The diagnosis of acute cytomegalovirus (CMV) infection is frequently based on a
      positive IgM result. False-positive reactions due to interfering infections may
      exist. Between August 1998 and May 1999, 62 patients were found to be IgM
      positive and IgG negative with the Axsym assay (Abbott, Germany). Serological
      testing for Epstein-Barr virus (EBV) was performed in these patients to detect
      any cross-reactivity due to acute mononucleosis. Additionally, the results of the
      CMV Axsym was evaluated in 40 patients with acute EBV infection. The results
      suggest that the CMV-IgM Axsym assay shows a lack of specificity due to acute EBV
      infection. Precautions must be taken when CMV-IgM Axsym results are interpreted.
      It seems necessary to confirm equivocal results with another technique and to
      take into account other clinical and biological observations.

PMID- 10968332
TI  - Candida glabrata oesophagitis in a patient without HIV infection.

PMID- 10968333
TI  - Vertebral osteomyelitis complicating Rothia dentocariosa endocarditis.

PMID- 10968334
TI  - Analysis of genotypes of human astrovirus isolates from hospitalized children in
      northeastern Germany.

PMID- 10968335
TI  - Activity of trovafloxacin, alone and in combination with other agents, against
      Enterobacteriaceae by time-kill analysis.

PMID- 10968336
TI  - Is a kit for identification of clinical yeasts correctly evaluated when released
      onto the market?

PMID- 10968337
TI  - Vitamin D and breast cancer: new approaches for hormonal therapy of breast
      cancer.

PMID- 10968338
TI  - Successful laparoscopic treatment of an abdominal pregnancy in the posterior cul
      de-sac.
AB  - PURPOSE: To describe the laparoscopic treatment of a first trimester abdominal
      pregnancy found in the cul-de-sac between the right uterosacral ligament and the
      rectum. CASE REPORT: A 32-year-old female presented to the emergency department
      with abdominal pain beginning a few hours prior to presentation. The serum
      betahCG level was 543 mIU/ml. An ultrasound examination revealed an empty uterus,
      bilateral normal fallopian tubes, and a large quantity of fluid in the pelvis.
      Secondary to patient symptoms, laparoscopy was performed. After the pelvis was
      irrigated to remove blood and clot, bilaterally normal fallopian tubes and
      ovaries were found. Further laparoscopic examination revealed an abdominal
      pregnancy implanted on the peritoneum between the right uterosacral ligament and
      the rectum. Hydrodissection was used to help elevate the peritoneum away from
      adjacent structures, and the products of conception were removed
      laparoscopically. CONCLUSION: In select first trimester patients with abdominal
      pregnancies, laparoscopic management can be performed.

PMID- 10968339
TI  - Nucleated red blood cell count and doppler ultrasound in low- and high-risk
      pregnancies.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of circulatory
      deterioration in small-for-gestational-age fetuses (SGA) on the nucleated red
      blood cell count (NRBC). PATIENTS AND METHODS: During a 12-month period 194
      patients with a complete NRBC count post-partum were enrolled in the study. Using
      pulsed wave colour Doppler ultrasound we recorded blood flow velocity waveforms
      from both uterine arteries and from the umbilical artery and/or from the fetal
      aorta. Patients were assigned to seven groups according to the results of the
      Doppler examination. Mean outcome measures were birthweight, gestational age at
      delivery, NRBC count, incidence of preeclampsia or SGA and need of neonatal
      intensive care. RESULTS: Significantly higher nucleated red blood cell counts
      than in all other groups were found in cases with abnormal Doppler findings in
      both uterine arteries and the umbilical artery and/or fetal aorta (p<0.001).
      These newborns had significantly lower birth weights (p<0.01, p<0.001), lower
      gestational age (p<0.001), an increased likelihood of caesarean section for
      clinical signs of fetal distress (p<0.001) and had to be transfered more
      frequently to the neonatal intensive care unit (p<0.01, p<0.001). CONCLUSION:
      Patients with abnormal Doppler velocimetry waveforms of the uterine arteries in
      the presence of an abnormal umbilical artery or fetal aorta Doppler findings have
      a high risk of prematurity, preeclampsia or delivering a small-for-gestational
      age newborn. Fetal response to uteroplacental insufficiency may lead to elevated
      nucleated red blood cells in the fetal blood. This fact might help to
      discriminate the small-for-gestational-age fetus who is growth-retarded and
      suffers from chronic placental insufficiency from the small but healthy fetus.

PMID- 10968340
TI  - Ovarian hyperstimulation can reduce uterine receptivity. A case report.

PMID- 10968341
TI  - The clinical significance of antenatal pathological Doppler findings in fetal
      middle cerebral artery compared to umbilical artery and fetal aorta.
AB  - PURPOSE: To compare the diagnostic capacity of fetal Doppler velocimetry in fetal
      middle cerebral artery to umbilical artery and fetal aorta to the prediction of
      fetal outcome. METHODS: 229 patients between 28 weeks of gestation (weeks) and 40
      weeks were examined by Doppler ultrasound in relationship to complications in
      gestation and labor, and fetal outcome. One thousand two hundred and seventy
      doppler blood flow velocity waveforms in the middle cerebral artery, umbilical
      artery and fetal aorta were recorded. Sensitivity of these vessels with regard to
      the prediction of intrauterine growth retardation, rate of cesarean section,
      preterm delivery and new-born depression was calculated. In all Doppler
      measurements there were no cases with absence of end-diastolic flow. RESULTS: The
      differences between pathological fetal outcome were not statistically
      significant, but diagnostic capacity of the middle cerebral artery velocimetry
      with regard to the prediction of pathological fetal outcome was on average 11%
      below the diagnostic capacity of the fetal aorta and umbilical artery.
      CONCLUSION: There is no benefit in examining fetal middle cerebral artery Doppler
      measurements in clinical routine in patients with normal velocity waveforms in
      the umbilical artery and fetal aorta.

PMID- 10968342
TI  - Ovarian mixed germ cell tumor composed of endodermal sinus tumor and immature
      teratoma: case report.

PMID- 10968343
TI  - Successful pregnancy following in vitro fertilization-embryo transfer despite
      imminent ovarian failure.
AB  - There have been previously published several anecdotal cases of women in apparent
      or imminent ovarian failure who subsequently ovulated and became pregnant. Many
      of these women had been treated with estrogen. A series of cases were reported
      where women with hypergonadotropic hypogonadism who failed to stimulate despite
      gonadotropin therapy were able to ovulate when treated with pharmacologic doses
      of estrogen alone or in combination with human menopausal gonadotropins.
      Presented herein is a case of a woman with imminent ovarian failure with tubal
      disease who failed to stimulate with gonadotropins alone but was successful with
      estrogen and gonadotropins. We believe this is the first successful case of
      hypergonadotropic hypogonadism to conceive by in vitro fertilization.

PMID- 10968344
TI  - Impaired intestinal active calcium absorption and reduction of serum 1alpha,
      25(OH)2D3 in streptozotocin-induced diabetic pregnant rats with hypocalcemia in
      their fetuses.
AB  - PURPOSE: The effects of maternal diabetes mellitus on fetal hypocalcemia were
      studied in streptozotocin-induced diabetic rats. MATERIALS AND METHODS:
      Experiments were performed using Wistar rats rendered diabetic with
      streptozotocin. Treatment with insulin was started in six diabetic pregnant rats
      after diabetes induction. On day 21 of gestation, cesarean section was performed
      and serum ionized calcium, parathyroid hormone and 1alpha, 25-dihydroxyvitamin D3
      were measured and the active intestinal calcium absorption was measured in mother
      rats using the everted gut sac technique. RESULTS: In untreated diabetic pregnant
      rats, serum 1alpha, 25-dihydroxyvitamin D3 and the active intestinal calcium
      absorption were significantly decreased, and the placental calcium transfer was
      disturbed compared with the control and insulin-treated groups. Furthermore,
      serum ionized calcium levels were markedly reduced in fetuses from untreated
      diabetic pregnant rats. However, these abnormalities of calcium metabolism in
      untreated diabetic rats could be corrected by treatment with insulin.
      CONCLUSIONS: These data indicate that diabetes mellitus in pregnant rats a
      contribute to negative calcium homeostasis which is probably related to the
      development of fetal hypocalcemia.

PMID- 10968345
TI  - Cetrotide confirmatory trial of cetrorelix/0.25 mg in 26 women undergoing ovarian
      stimulation with recombinant follicle stimulating hormones for IVF, ICSI and
      embryo transfer (ET).
AB  - BACKGROUND: There have been numerous double-blind, randomised, dose-finding
      studies of the gonadotrophin-releasing hormone (Gn-RH) antagonist Ganirelix (Org
      37462) and the Gn-RH antagonist Cetrorelix. METHODS: We performed a clinical
      trial with 26 patients undergoing ovarian stimulation with the recombinant human
      follicle stimulating hormone (FSH) by applying rec. FSH in a flexible daily dose,
      depending on the estradiol levels of the patient, from day 3 of the cycle onwards
      in a controlled ovarian hyperstimulation (COH) protocol. A single dose of 0.25 mg
      was injected daily subcutaneously from day 7 of the cycle onwards until the day
      of HCG application. The recombinant FSH dose was adjusted according to ovarian
      response. Fifteen patients were treated for IVF and nine for ICSI. In two
      patients egg retrieval was not performed. Estradiol and LH levels were measured
      on the day of HCG application. RESULTS: The mean number of recovered oocytes in
      the 24 patients was 5.5. A fertilisation rate of 64% was achieved in the IVF
      group and 69% in the ICSI group. In Germany a maximum of three embryos per
      patient is permitted to be transferred. Pregnancy occurred in ten patients: 5 IVF
      patients and 5 ICSI patients. In this small group of IVF patients a 33% pregnancy
      rate per follicular puncture and a 50% pregnancy rate per embryo transfer
      resulted. The ICSI group showed a 55% pregnancy rate per follicular puncture and
      a 62% pregnancy rate per embryo transfer. CONCLUSION: Within an IVF/ET, ICSI
      programme the Gn-RH-antagonist Cetrorelix in combination with rec. FSH gave
      optimal pregnancy results.

PMID- 10968346
TI  - Reference ranges and standard percentile-curves for the Doppler indices RI and
      S/D ratio of the fetal middle cerebral artery. Color Doppler measurements in a
      perinatal centre.
AB  - PURPOSE: To perform reference ranges and standard percentile-curves for the
      Doppler indices resistance index (RI) and systolic/diastolic (S/D) ratio of the
      fetal middle cerebral artery, periodical color doppler sonographic measurements
      of 70 pregnant women in the 3rd trimester of pregnancy were done. METHODS: 600
      Doppler flow measurements of the fetal middle cerebral artery between 28 and 40
      weeks of gestation were performed. The patients had no previous obstetric
      complications, no apparent medical problems and no complications in pregnancy and
      labor. Percentiles curves were performed for the RI and the S/D ratio from the
      10th percentile up to the 90th percentile. RESULTS: In the 3rd trimester of
      pregnancy fetal cerebral circulation shows an increase of the diastolic component
      and simultaneous decrease in cerebral resistance. The average S/D ratio in week
      29 is 8.0, in week 34 6.0 and in the 40th week 3.5. The RI decrement is from 0.88
      to 0.67. Other groups demonstrated similar ranges however absolute data are
      different. CONCLUSION: The increase in the diastolic component in the middle
      cerebral artery of the last third of the pregnancy demands reference ranges by
      using percentile curves. Knowledge of the reference range helps to discriminate
      between a normal fetal situation and disease. Because of different absolute
      ranges in the literature each perinatal centre should develop their own data.

PMID- 10968347
TI  - Does hysterectomy without salpingo-oophorectomy influence the reoperation rate
      for adnexal pathology? A retrospective study.
AB  - OBJECTIVE: The aim of this study was to assess if the abdominal, vaginal and
      laparoscopic approach to hysterectomy can affect the incidence of ovarian or
      adnexal pathology after hysterectomy without salpingo-oophorectomy. METHODS: In
      this study 17 cases out of 617 hysterectomies were found to have development of
      adnexal pathology; reoperation rate was 2.75%. RESULTS: The reoperation rate was
      significantly different (p < 0.006) in the observed approaches to hysterectomy
      (TAH 5.67%, VH 0.69%, LH 3.18%). The greatest difference was found between the
      abdominal and vaginal groups. CONCLUSION: Our study results have sufficiently
      shown that the relationship of a number of factors (age, primary histologic
      findings, smaller peritoneal trauma) had an important impact on a significant
      difference in reoperation rate between vaginal, laparoscopic and namely abdominal
      hysterectomies in female patients with preserved adnexa.

PMID- 10968348
TI  - Evaluation of the secretion of the atrial natriuretic factor (ANF) after
      laparotomy.
AB  - BACKGROUND: ANF is a potent diuretic, natriuretic and vasorelaxant hormone. The
      objective of the present study was to examine the effect of opioid receptor
      stimulation by morphine after surgery on endogenous ANF production and diuresis.
      METHODS: Prospectively, 11 women undergoing surgery for either uterine
      leiomyomas, chronic pelvic discomfort or desire for definitive contraception by
      laparotomy were evaluated. Venous samples were collected at fixed times.
      Concentrations of ANF were measured by commercially available radioimmunoassay
      test kits. Statistical analysis was performed by the Friedman Two way ANOVA.
      Kruskal-Wallis 1-way ANOVA and Mann-Whitney U-Wilcoxon Rank Sum W Test. The level
      of significance was set at probability below 0.05. RESULTS: There were
      statistically significant changes in the serum levels of ANF (p=0.0028), in pain
      score (p<0.0001) and urinary flow rate (p<0.0001) after operation, while the
      diastolic (p=0.0671) and systolic (p=0.0543) blood pressure showed slightly
      significant changes. CONCLUSION: Our results show that i.v. administered morphine
      induces a potent diuretic effect via activation of opioid receptors and suggest
      that this effect is due to the enhanced release of ANF. However the mechanism by
      which morphine induces the ANF release remains to be evaluated.

PMID- 10968349
TI  - A case report of a pedunculated uterine leiomyosarcoma.

PMID- 10968350
TI  - The applicability of biochemical markers of bone metabolism for predicting the
      risk of bone fractures and for the assessment of bone tissue resorption in the
      course of osteoporosis.
AB  - The role of increased metabolism of bone tissue as a risk factor for bone
      fractures in the course of osteoporosis has been investigated. The importance of
      the assay of biochemical markers of bone remodelling for determining the degree
      of bone tissue resorption has been evaluated.

PMID- 10968351
TI  - Ovarian remnant syndrome: a case report and review of the literature.
AB  - The ovarian remnant syndrome in an unusual complication of bilateral
      oophorectomy, usually presenting with pelvic mass and pain. A case of the
      syndrome is described in a 35-year-old woman with a history of abdominal
      hysterectomy and bilateral oophorectomy. We suggest that ovarian remnant syndrome
      should be considered in the differential diagnosis of chronic pelvic pain after
      recorded oophorectomy.

PMID- 10968353
TI  - Argyrophilic proteins of nucleolar organizer regions (AgNORs) in fallopian tube
      carcinomas.
AB  - Forty-four patients diagnosed with primary cancer of the fallopian tube (PFTC)
      were analyzed with regard to AgNORs expression, morphological classification,
      clinical stage and survival rate. Twenty-seven patients were FIGO stage I, 7 FIGO
      II and 10 FIGO III. Histological classification of PFTC revealed 18 endometrioid
      types, 9 serous, 7 undifferentiated, 6 urothelial, 2 clear cell and 2 another
      type of (intestinal, squamous cell) cancer. Histological grading revealed 11 G1,
      16 G2 and 17 G3 tumors. The number of AgNORs per nucleus ranged from 1 to 7, mean
      2.54+/-0.77. The smallest number of silver stained NORs was observed in the
      endometrioid type (mean 2.32+/-0.62) and the biggest number of AgNORs in
      undifferentiated carcinoma (mean 3.05+/-0.82). There was no correlation between
      number of AgNORs and AgNOR area/nuclear area ratio and survival (p=0.71),
      histological stage or histological type of PFTC. There was a correlation between
      the number of AgNORs among tumors with histological grade 1 and grade 3
      (p=0.023), and grade 2 and grade 3 (p=0.045). However, there was no correlation
      between AgNOR number and survival rate in these groups.

PMID- 10968352
TI  - Successful treatment of an advanced ovarian serous cystadenocarcinoma in
      pregnancy with cisplatin, adriamycin and cyclophosphamide (CAP) regimen. Case
      report.

PMID- 10968354
TI  - Levator ani muscle activity in pregnancy and the postpartum period: a myoelectric
      study.
AB  - The levator ani (LA) is a muscle of evacuation and acts as well to support the
      pelvic viscera. An increase of the intra-abdominal pressure beyond the
      physiologic limits and visceral overload are speculated to interfere with LA
      functional activity. This consideration was a stimulus to study the effect of
      pregnancy on the LA muscle. The EMG activity of the LA muscle was recorded before
      and during pregnancy and after delivery in 36 women (mean age 27.2+/-3.1 years,
      20 multigravida, 16 primigravida). A needle electrode was inserted into the
      muscle and LA activity was recorded at rest, and on squeezing and straining in
      both the erect and recumbent position. In the erect position, the resting and
      squeezing EMG activity during the first 8 weeks of pregnancy, showed no
      significant difference (p>0.05) from that before pregnancy, and after that,
      increased progressively and significantly until delivery. On straining, the EMG
      activity showed no significant difference from that before pregnancy in the first
      8 weeks, and after that, decreased progressively and significantly till delivery.
      In the recumbent position, the LA EMG registered similar activity to that in the
      erect position but with significantly lower values (p<0.05). The reduction in the
      LA EMG activity was more evident in the multi-than in the primigravida. In the
      postpartum period, no LA EMG activity was recorded in the first month; the
      activity increased progressively after that time to reach the pre-pregnancy level
      in the forth postpartum month. In conclusion, pregnancy interferes with EMG and
      functional activity of the LA from the 8th week onwards due to the progressively
      increasing size and weight of the uterus. This effect was most marked in the last
      12 weeks. Delivery seems to maximally inhibit the LA activity in the first
      postpartum month. Excessive LA traumatization may eventually lead to levator
      dysfunction syndrome.

PMID- 10968355
TI  - Anti-endometrial IgM autoantibodies in endometriotic patients: a preliminary
      study.
AB  - Japanese herbal medicines (Kampo medicines) are usually the third most popular
      choice among medicines for treatment of endometriosis in Japan. This traditional
      therapy is used to improve various signs and symptoms of endometriosis without
      decreasing serum estradiol levels or causing menstrual disorders. We used flow
      cytometry to examine and compare the effects of the Kampo therapy and danazol on
      anti-endometrial humoral immunity. Autoantibodies against endometrial epithelial
      cell lines and endometrial stromal cells were detectable in all the examined sera
      of men and women irrespective of the presence of endometriosis. Moreover, no
      significant increase in anti-endometrial antibodies was found in endometriotic
      patients. Anti-endometrial antibodies included Ig-gamma chain, Ig-mu chain, Ig
      kappa chain, and Ig-lambda chain indicating polyclonal B cell activation in the
      endometriotic patients. Absorption tests of nonspecific antibodies with cervical
      cancer cells or ovarian cancer cells revealed that endometriotic patients had
      higher levels of endometrium-specific autoantibodies than did non-endometriotic
      healthy women. IgM fractions from endometriotic patients and healthy women
      differed in their effect on growth of endometrial adenocarcinoma cells. Therapy
      with the herbal compounds Keishi-bukuryo-gan but not danazol therapy, gradually
      decreased the tissue-specific anti-endometrial IgM antibody levels. These results
      indicate that tissue-specific anti-endometrial IgM may be a useful therapeutic
      marker for endometriotic patients treated with Keishi-bukuryo-gan and that
      endometrial tissue-specific immune disorders play specific roles in the
      pathogenesis or development of endometriosis.

PMID- 10968356
TI  - Histomorphometric aspects of adult castrated rat endometrium after the use of
      estrogen, progesterone and tamoxifen.
AB  - The aim of this study was to analyse the morphologic and morphometric aspects of
      endometrium in rats receiving hormone replacement therapy with conjugated equine
      estrogen (CEE), medroxyprogesterone acetate (MPA) and tamoxifen (TMX). Thirty
      five adults rats, 2-3 months of age were ovariectomized four days prior to using
      the drugs. Rats were divided according to the following treatments for 60 days:
      CEE (50 microg); CEE/MPA (50 microg/2 mg); MPA (2mg); TMX (250 microg); vehicle
      (propyleneglycol). Fragments of endometrium were removed and analysed by light
      microscopy. The endometrium suffered evident morphologic modifications under the
      action of hormones and TMX. The endometrium was significantly thicker in the CEE,
      CEE/MPA and TMX group when compared to the control, however the MPA group showed
      no differences when compared to the control group.

PMID- 10968357
TI  - Significance of changes in lipid peroxides and antioxidant enzyme activities in
      pregnant women with preeclampsia and eclampsia.
AB  - This review addresses the general hypothesis that the pathogenesis of
      preeclampsia and eclampsia are related to an imbalance of increased oxidative
      stress and lipid peroxidation coupled with a deficiency of antioxidant
      protection. Accordingly, this study was initiated to assess total antioxidant
      status and free-radical activity in preeclampsia and eclampsia. The patients
      studied were 44 healthy pregnant women and 45 women with hypertension classified
      as having preeclampsia (n=27), and eclampsia (n=18). The serum levels of lipid
      peroxide were significantly increased (p<0.0001) and antioxidant enzyme
      activities (superoxide dismutase and glutathione levels) in erythrocytes were
      significantly decreased (p<0.0001) in women with preeclampsia and eclampsia
      compared with the controls. The groups of preeclampsia and eclampsia had similar
      values of catalase activities as the controls (p>0.05). There were no
      correlations between serum levels of lipid peroxide and antioxidant enzyme
      activities or systolic-diastolic blood pressure of pregnant women with
      preeclampsia and eclampsia. The mean systolic and diastolic blood pressure, the
      serum lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels of
      preeclamptic and eclamptic women were high, whereas haemoglobin (Hb), Hematocrit
      (Htc) and platelet levels were lower than those of the control subjects
      (p<0.0001). There were no differences in mean gestational week, whereas the mean
      age of eclamptic women was lower than that of the other two groups (p<0.001). The
      serum levels of Alanine-transaminase (ALT) and urea in eclamptic women were
      significantly higher compared with the other two groups (p<0.0001), whereas
      creatinine levels were lower than those of the other two groups (p<0.05). Our
      findings give support to those few studies considering lipid peroxidation as an
      important factor in the pathogenesis of preeclampsia and eclampsia. Further
      studies are needed to clarify the relations between lipid peroxidation and
      antioxidative function and their pathophysiological significance in preeclampsia
      and eclampsia.

PMID- 10968358
TI  - Uterine malformations and pregnancy losses: is cervical cerclage effective?
AB  - For many years, we and others have reported the efficacy of cervical cerclage in
      the prevention of miscarriage in patients with uterine malformations. In this
      paper the experience of 275 cases collected between 1978 and 1998 is reported.
      Our data indicate that cervical cerclage is effective in preventing miscarriages,
      prevalently in those pregnancies bearing uterine malformations with simultaneous
      cervical incompetence.

PMID- 10968359
TI  - Removal of a voluminous serous papillary paraovarian cystadenoma by endoscopic
      surgery. A case report.
AB  - A case of a right paraovarian cystadenoma (7.3 litres) in a young woman, 19 years
      old, who was treated by laparoscopy is described. The advantages of endoscopic
      surgery are evaluated.

PMID- 10968360
TI  - The functional organization of the nucleolus in proliferating plant cells.
AB  - The nucleolus is a prominent nuclear organelle which morphologically expresses
      all functional steps necessary for the synthesis of ribosomes, from transcription
      of rRNA genes to the assembly and maturation of preribosomal particles and their
      transport to the cytoplasm. Structurally, the nucleolus contains some basic
      components common to practically all cell types, namely fibrillar centers (FCs),
      the dense fibrillar component (DFC), and the granular component (GC); however,
      the organization and distribution of these components is highly variable,
      depending on cell identity and functional status. The different steps of ribosome
      biogenesis are not strictly correlated with the structural components of the
      nucleolus. Thus, FCs are most likely the anchoring sites for the accumulation of
      rDNA, and the sites where the assembly of transcription complexes takes place,
      but transcription of rRNA genes actually occurs at discrete points in the
      transition zone between FCs and the DFC. The DFC is a structurally homogeneous,
      but functionally heterogeneous component in which transcription and some early
      and advanced steps of pre-rRNA processing develop successively in a gradual
      fashion, from transition with FCs to transition with the GC. Finally, the GC is
      the site of the later steps of preribosomal processing, including the final
      assembly of ribosomal proteins for the export of mature particles to the
      cytoplasm. The rate of ribosome biogenesis, as well as the structure of the
      nucleolus, are highly influenced by the proliferation status of the cell, and by
      factors regulating cell cycle progression. These factors are nucleolar proteins,
      such as nucleolin, which are targets of signal transduction mechanisms, being at
      the same time regulators of key steps in preribosome synthesis and processing.
      Thus, many features of the nucleolus, such as the structural organization of its
      components, the level and distribution of certain nucleolar proteins and, in
      general, the rate of ribosome biogenesis, show profound variations throughout
      cell cycle periods. Particularly interesting is the behavior of the nucleolus
      during mitosis, in which its structure is disorganized and its activity is
      stopped, even though the individual transcription and processing complexes are
      not disassembled, but carried from one cell generation to the next one in such a
      way that the daughter-cell nucleoli are built with materials coming from the
      parent-cell nucleolus. Transcription complexes remain assembled at the
      chromosomal nucleolar organizer in which the rRNA genes are clustered, and
      processing complexes are carried at the chromosome periphery, and then they are
      organized into discrete entities called prenucleolar bodies, whose fusion,
      together with the resumption of transcription and processing, originates the new
      nucleolus.

PMID- 10968361
TI  - Genome instability in human tumorigenesis: microphotometry of interphase nuclei
      and pathologic mitoses reveals dysplasia.
AB  - Tumorigenesis goes with genome instability comprising point mutations and gross
      chromosome aberrations due to defective DNA repair mechanisms and multiple
      overrun of cell cycle checkpoints. Pathologic mitoses (CDFs) occur in human
      precancers and cancers and were detected by nuclear DNAs deviating more or less
      than 0.5 c from 4.0 c values. Abundant CDFs were recorded above 4.5 c threshold
      in lesions of the uterine cervix and the stomach. Low-grade dysplasias and well
      differentiated carcinomas showed 3%-10% CDFs, high-grade dysplasias 30%-44% CDFs
      in total divisions. Poorly differentiated cancers comprised some 50% CDFs. Most
      telophase CDFs showed asymmetric morphology and unbalanced DNA content in their
      corresponding "halves". CDFs precede DNA aneuploidy of interphase nuclei not only
      in precancers, but also in cancer. Chromatin bridges and lagging chromosomes
      suggest that unbalanced telophases are caused by somatic nondisjunction. Tumour
      progression from low-grade to high-grade dysplasia and cancer is characterised by
      recurrent shifts from 2 c to 4 c interphase nuclei and a remarkable increase in
      the 5 c exceeding rate. Clonal selection is the gateway in tumorigenesis for
      aberrant karyotypes.

PMID- 10968363
TI  - Immunoelectron microscopic demonstration of the membrane proteases aminopeptidase
      N/CD13 and dipeptidyl peptidase IV/CD26 in normal and neoplastic renal
      parenchymal tissues and cells.
AB  - Aminopeptidase N (APN, CD13) and dipeptidyl peptidase IV (DPP IV, CD26) are
      transmembrane ectoenzymes occurring in a wide variety of cells. They are involved
      in tumour cell invasion and the formation of metastases. A basis for further
      information about these enzymes is the exact ultrastructural localization in
      normal and malignant cells. In this paper, we demonstrate the precise subcellular
      localization of the membrane peptidases APN and DPP IV on the cell surfaces in
      renal tissues, renal cell carcinoma, cultured renal parenchymal cells and
      cultured renal carcinoma cells. Using cryo-ultramicrotomy of weakly fixed tissues
      and cells in combination with indirect immunogold labelling, both membrane
      peptidases were detectable on the external cell surfaces. They showed different
      ultrastructural expression patterns. Both membrane peptidases were abundantly
      labelled on the external cell surfaces of human kidney proximal tubular cells.
      The expression pattern of APN/CD13 and DPP IV/CD26 in single labelling was
      confirmed by a successive double labelling technique. The immunolabelling of CD13
      on cultured renal parenchymal cells showed a stronger expression then in cells in
      vivo, but CD26 could not be found. In renal cell cancer (mixed clear
      cell/chromophilic, poorly differentiated and clear cell type, moderately
      differentiated) CD13 and CD26 were labelled as in benign renal tissue, but CD26
      appeared overexpressed. On the renal carcinoma cells Caki-1 and Caki-2, only one
      of the two peptidases could be found. CD13 was present non-homogeneously in Caki
      1, where the enzyme appeared to form clusters. When CD26 on the cultured renal
      carcinoma cells Caki-2, is compared with renal proximal tubular cells and renal
      carcinoma cells in tissue sections, a reduced expression is observed. CD13 was
      not detected in Caki-2, and CD26 was not found in Caki-1. These small changes on
      the cell surfaces can only be detected by electronmicroscopic methods. The
      differences in the distribution of APN/CD13 and DPP IV/CD26 in normal and
      malignant cells are discussed in connection with literature. Further
      investigations, especially labelling studies on other neoplastic tissues and
      cells, will be necessary in order to explain the precise role these membrane
      peptidases in malignancies.

PMID- 10968362
TI  - Early progression stage of malignancy of uterine cervical dysplasia as revealed
      by immunohistochemical demonstration of increased DNA-instability.
AB  - The degree of DNA-instability as revealed by the immunohistochemical staining
      with anti-single-stranded DNA antibody after acid hydrolysis (DNA-instability
      test) was used as a marker of malignancy. This was applied to mild dysplasia (42
      cases), moderate dysplasia (43 cases), severe dysplasia (27 cases), squamous cell
      carcinoma in situ (CIS) (21 cases), invasive squamous cell carcinoma (SCC) (31
      cases) and normal (7 cases) human uterine cervix. The expression of tumour
      suppressor gene p53 and oncogene bcl-2 was detected immunohistochemically.
      Proliferative activity was evaluated by PCNA immumohistochemistry and the
      quantitative analysis of the number, mean area, the largest area and maximum
      shape irregularities of AgNOR in a nucleus were performed for all these cases.
      The distribution of numeric chromosomal aberrations of chromosome 17 was also
      investigated in some of these cases. The results showed that 31 SCC (100%), 21
      CIS (100%), 21 severe dysplasia (77.77%), 28 moderate dysplasia (65.11%), and 14
      mild dysplasia (33.33%) were positively stained by the DNA-instability test
      diffusely or sporadically, indicating their malignancy. Reflecting the malignant
      character, these cases showed a remarkable increase in the PCNA-index with the
      loss of polarity of PCNA positive cell distribution and also an increase in
      number, mean and largest sizes and maximum shape irregularity of AgNOR dots. The
      mean chromosome index for chromosome 17, p53 and bcl-2 immunostaining positivity
      were also found to be significantly increased in moderate and severe dysplasia
      and in cancerous cases in comparison to normal and mild dysplasia cases.
      Moreover, the DNA-instability-test positive dysplasia cases showed statistically
      significant increased values of PCNA-index, AgNOR parameters, mean chromosome
      index, p53 and bcl-2 expression in comparison to those of DNA-instability-test
      negative dysplasia cases. In conclusion, some mild dysplasia (33.33%) and most of
      the moderate (65.11%) and severe dysplasia (77.77%) were regarded as malignant in
      nature, existing at an early stage of progression of malignancy.

PMID- 10968364
TI  - Cholinergic nerve fibres associated with the microvessels of the human cerebral
      cortex: a study based on monoclonal immunocytochemistry for choline
      acetyltrasferase.
AB  - The distribution of cholinergic nerve fibres associated with the microvasculature
      of the human parietal cerebral cortex was investigated by immunocytochemistry,
      employing monoclonal antibodies against choline acetyl-transferase, the
      acetylcholine-synthesizing enzyme. The results revealed strongly immunoreactive
      nerve fibres in the tunica adventitia of arterioles penetrating the superficial
      cortical layers from the pial vasculature. Networks of stained nerve fibres were
      seen within the tunica muscularis of the radially directed arterioles that cross
      the intermediate and deep cortical laminae, and of their transverse and recurrent
      branches. Tiny positive nerve fibres were also seen around the cortex
      capillaries, some reaching the endothelial cells. The morphological data support
      the involvement of acetylcholine in microvasculature local regulation, possibly
      with a differentiated role in the arterioles and capillaries.

PMID- 10968365
TI  - Tissue distribution of bovine cystatin C analysed by in situ hybridisation.
AB  - Cysteine proteinase inhibitors of the cystatin superfamily have been identified
      in many living organisms. However, knowledge of the tissue distribution of such
      inhibitors is limited. To elucidate this distribution in mammals, we have
      investigated the expression of the gene for cystatin C, belonging to cystatin
      family II, in several bovine tissues. In situ hybridisation with a digoxigenin
      labelled cRNA probe demonstrated a high concentration of bovine cystatin C mRNA
      in the secretory epithelial cells of the choroid plexus, and also intense
      staining in cells of lymphoid tissue and in Sertoli cells. Cystatin C mRNA was
      also present in scattered neurons and glial cells throughout the cerebrum and the
      cerebellum. In the submandibular gland, specific mRNA was found mainly in
      striated intralobular ducts and interlobular ducts. The expression of cystatin C
      in brain tissue is of particular interest, as the inhibitor appears to be
      involved in certain neurological diseases. The main production of cystatin C
      within the brain is believed to be by astrocytes. However, this work shows that
      also neurons from young, normal individuals express cystatin C.

PMID- 10968366
TI  - In situ-PCR for the detection of Mycobacterium paratuberculosis DNA in paraffin
      embedded tissues.
AB  - Molecular biological techniques have permitted the rapid and sensitive detection
      of the Mycobacterium paratuberculosis genome in infected tissues, most commonly
      by polymerase chain reaction amplification of sequences in the IS900 DNA
      insertion sequence. The aim of this work was the detection of M. paratuberculosis
      DNA in ovine tissues by in situ-polymerase chain reaction, which is sensitive and
      localises the signal within the tissue sample. Paraffin embedded tissues from
      three acid-fast positive ovine guts with classical lesions of paratuberculosis,
      and from negative control samples were tested. A 413-bp fragment of the IS900
      sequence was amplified in-situ and hybridised to an internal PCR-synthesised
      digoxygenin-labelled probe. The samples from sheep affected by paratuberculosis
      clearly showed cell-specific cytoplasmic signals in mucosal and submucosal
      macrophages. This technique could be useful both in the diagnosis and study of
      the pathogenesis of infections in which involvement of M. paratuberculosis is
      suspected.

PMID- 10968367
TI  - Detection of bromodeoxyuridine in formalin-fixed tissue. DNA denaturation
      following microwave or enzymatic digestion pretreatment is required.
AB  - The present study was designed to assess the influence of antigen retrieval
      and/or DNA denaturation on the quantitative estimation of bromodeoxyuridine
      (BrdU) in formalin-fixed paraffin-embedded tissue. Specimens of small intestine
      from rats injected with BrdU were routinely fixed and embedded in paraffin. For
      antigen retrieval, sections were pretreated with microwave irradiation or
      enzymatically (pepsin or trypsin). Acid hydrolysis was used as a DNA denaturation
      method. Immunostaining of BrdU-labeled cells was performed. The best results,
      regarding tissue morphology and immunostaining, were obtained with microwave
      pretreatment followed by acid hydrolysis. Enzymatic pretreatment resulted in
      damage of tissue morphology and/or high background staining. Microwave alone,
      without DNA denaturation, resulted in a lower percentage of BrdU positive cells.
      The significance of validation studies is emphasized when the level of positivity
      for a prognostic marker, such as BrdU, is assessed.

PMID- 10968368
TI  - Fluorescent in situ hybridisation on tissue sections: a quantitative approach
      with confocal laser scanning microscopy.
AB  - The use of fluorescent detection methods in association with digital microscopy
      technologies is an innovative approach for tissue localisation of messenger RNA.
      The success of such methods relies on the tissue preservation, local availability
      of the probe and on the existence of high resolution tridimensional analysis
      systems. Cryostatic sections, mild denaturation, short oligonucleotide probes
      (20mer) and confocal laser scanning microscopy allow the fulfillment of all these
      conditions avoiding photobleaching and tissue autofluorescence. In this paper, we
      describe in detail a method for in situ hybridisation set up with digoxigenin
      coupled oligonucleotide complementary to beta-actin mRNA as a probe and an anti
      hapten fluorescent antibody as second step for detecting specific hybridisation.
      Fluorescence was analysed by means of a confocal laser scanning microscope (CLSM)
      that provides images with low out-of-focus blurring also with relatively low
      numerical aperture (NA) objectives. We propose also an easy method to perform
      semi-quantitative thresholding analysis which allows to discriminate between
      background and specific signal.

PMID- 10968369
TI  - Production and characterization of antibodies directed against the human
      melatonin receptors Mel-1a (mt1) and Mel-1b (MT2).
AB  - We report the production of polyclonal antibodies directed against the human
      melatonin receptors Mel-1a (mt1) and Mel-1b (MT2) by means of antigenic synthetic
      peptides with sequences unique to these proteins. Immunostaining on NIH3T3 cells
      stably transfected with Mel-1a and Mel-1b cDNA gave intense reactions. Neither
      the preimmune serum nor cross-tested antisera showed any reactivity. These
      polyclonal antibodies will be essential immunocytochemical tools to study the
      human melatonin receptors distribution at subcellular level.

PMID- 10968370
TI  - Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected
      cells.
AB  - Two molecules that regulate cell fusion have been identified and designated
      fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a
      glycosylated heavy chain and a nonglycosylated light chain that are disulfide
      linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is
      identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional
      molecule: that is, fusion regulator, amino acid transporter, integrin regulator,
      comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several
      aspects of the structure and function of the FRP-1 system are reviewed: fusion
      regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the
      FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The
      FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant
      cell formation of blood monocytes. Monoclonal antibodies against human FRP-1
      heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple
      steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy
      chain supports amino acid transport activity and the FRP-1 light chains have
      recently been cloned as amino acid transporters that require association with the
      heavy chain to exhibit their activity. Novel pathways for monocyte-dependent
      regulation of T-cell activation have recently been found that are mediated by the
      FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic
      cellular functions.

PMID- 10968371
TI  - Regulation of the adhesion versus cytotoxic functions of the Mac
      1/CR3/alphaMbeta2-integrin glycoprotein.
AB  - Mac-1/CR3 functions as both an adhesion molecule mediating the diapedesis of
      leukocytes across the endothelium and a receptor for the iC3b fragment of
      complement responsible for phagocytic/degranulation responses to microorganisms.
      Mac-1/CR3 has many functional characteristics shared with other integrins,
      including bidirectional signaling via conformational changes that originate in
      either the cytoplasmic domain or extracellular region. Another key to its
      functions is its ability to form membrane complexes with
      glycosylphosphatidylinositol (GPI)-anchored receptors such as Fc gammaRIIIB
      (CD16b) or uPAR (CD87), providing a transmembrane signaling mechanism for these
      outer membrane bound receptors that allows them to mediate cytoskeleton-dependent
      adhesion or phagocytosis and degranulation. Many functions appear to depend upon
      a membrane-proximal lectin site responsible for recognition of either microbial
      surface polysaccharides or GPI-linked signaling partners. Because of the
      importance of Mac-1/CR3 in promoting neutrophil inflammatory responses,
      therapeutic strategies to antagonize its functions have shown promise in treating
      both autoimmune diseases and ischemia/reperfusion injury. Conversely, soluble
      beta-glucan polysaccharides that bind to its lectin site prime the Mac-1/CR3 of
      circulating phagocytes and natural killer (NK) cells, permitting cytotoxic
      degranulation in response to iC3b-opsonized tumor cells that otherwise escape
      from this mechanism of cell-mediated cytotoxicity.

PMID- 10968372
TI  - Interaction between the human NK receptors and their ligands.
AB  - NK cells are physiologically important in a number of contexts: mediating
      immunity against viruses, intracellular bacteria and parasites, and in anti
      tumour immune responses. Moreover, in addition to these overtly immune protective
      functions, NK cells also mediate a variety of homeostatic functions, particularly
      in the regulation of haematopoesis and they may have an important role to play in
      the maintenance and development of placentation; certainly NK cells are a major
      component of the lymphocyte population of the decidua. The behaviour of the NK
      cell in these various situations is regulated by a large number of distinct
      receptors that transmit positive and negative signals. The balance of these
      signals determines whether the NK cell does nothing or is activated to
      proliferate, kill or secrete a wide range of cytokines and chemokines. In this
      review the structure and function of a number of molecules found on the NK cell
      surface are discussed, particular emphasis being placed on the molecular details
      of the recognition of target cell classical class I HLA molecules by Killer cell
      Immunoglobulin-like Receptors (KIR) and the binding of the non-classical class I
      molecule HLA-E to the heterodimer formed by the association of CD94 with various
      members of the NKG2 proteins.

PMID- 10968373
TI  - Adhesion molecule expression in acute and chronic exercise.
AB  - Adhesion molecules expressed on leukocytes and the vascular endothelial lining
      include the selectins, integrins, members of the immunoglobulin superfamily, and
      mucins. The changes in their expression that develop with acute and chronic
      exercise are briefly reviewed. Adhesion molecules are thought to modulate
      leukocyte trafficking, accounting for changes in the counts and possibly also the
      functional activity of various leukocyte subsets during and following an acute
      bout of physical activity. Some of the changes in the surface density of adhesion
      molecules can be explained through the action of epinephrine and other humoral
      factors on their expression, but an influence of sympathetic nerve terminals on
      cells sequestered in the spleen and liver, and an influx into the general
      circulation of leukocytes of differing phenotype also appear to be involved.

PMID- 10968375
TI  - Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a
      multicenter case-control study. Collaborating Centers.
AB  - Occupational exposures were investigated in a multicenter case-control study of
      clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a
      chronic diffuse interstitial lung disease of unknown etiology. Results are based
      on 248 cases, aged 20-75 years, diagnosed at 16 referral centers between January
      1989 and July 1993. There were 491 controls ascertained by random digit dialing
      and matched to cases on sex, age, and geographic region. Data were collected
      using a standard telephone questionnaire. Occupational factors were based on a
      detailed history of jobs lasting 6 months or more and job activity, hobby, and
      specific substance checklists. Several occupational factors, adjusted for age and
      smoking in conditional multivariate logistic regression analyses, were
      significantly associated with IPF: farming (odds ratio (OR) = 1.6, 95% confidence
      interval (CI): 1.0, 2.5); livestock (OR = 2.7, 95% CI: 1.3, 5.5); hairdressing
      (OR = 4.4, 95% CI: 1.2, 16.3); metal dust (OR = 2.0, 95% CI: 1.0, 4.0); raising
      birds (OR = 4.7, 95% CI: 1.6, 14.1); stone cutting/polishing (OR = 3.9, 95% CI:
      1.2, 12.7); and vegetable dust/animal dust (OR = 4.7, 95% CI: 2.1, 10.4).
      Interaction was detected between smoking and exposure to livestock (p = 0.06) and
      farming (p = 0.08). Results confirm previous studies showing increased risk
      associated with dusty environments.

PMID- 10968374
TI  - Exposure to nitrosamines, carbon black, asbestos, and talc and mortality from
      stomach, lung, and laryngeal cancer in a cohort of rubber workers.
AB  - There is sufficient evidence for an excess occurrence of stomach and lung cancer
      among rubber workers. However, evidence for causal associations with specific
      exposures is still limited. A cohort of 8,933 male German rubber workers was
      followed for mortality from January 1, 1981 through December 31, 1991. Work
      histories were reconstructed using routinely documented cost center codes. For
      each cost center code, calendar time-and plant-specific levels of exposure to
      nitrosamines, asbestos, talc (low, medium (m), and high (h)), and carbon black
      (two levels) were estimated by industrial hygienists. Rate ratios (RR) and 95%
      confidence intervals (CI) were calculated using Cox proportional hazards models,
      with the lowest exposure level used as the reference category. Exposure was
      lagged 10 years to account for latency. Exposure-response relations between
      exposure to asbestos and lung cancer mortality (RRm = 1.3, 95% CI: 0.9, 1.9; RRh
      = 2.0, 95% CI: 0.9, 4.1) and between exposure to dust (talc and asbestos
      combined) and stomach cancer mortality (RRm = 1.8, 95% CI: 0.9, 3.8; RRh = 2.7,
      95% CI: 1.0, 7.1) were observed. Exposure to nitrosamines was not associated with
      mortality from stomach or lung cancer. These results suggest that the increased
      mortality from lung and stomach cancer among rubber workers is associated with
      exposure to asbestos and dust, respectively.

PMID- 10968376
TI  - Effects of a community-wide health education program on cardiovascular disease
      morbidity and mortality: the Stanford Five-City Project.
AB  - The authors examined changes in morbidity and mortality from 1979 through 1992
      during the Stanford Five-City Project, a comprehensive community health education
      study conducted in northern California. The intervention (1980-1986), a multiple
      risk factor strategy delivered through multiple educational methods, targeted all
      residents in two treatment communities. Potentially fatal and nonfatal myocardial
      infarction and stroke events were identified from death certificates and hospital
      records. Clinical information was abstracted from hospital charts and coroner
      records; for fatal events, it was collected from attending physicians and next of
      kin. Standard diagnostic criteria were used to classify all events, without
      knowledge of the city of origin. All first definite events were analyzed;
      denominators were estimated from 1980 and 1990 US Census figures. Mixed model
      regression analyses were used in statistical comparisons. Over the full 14 years
      of the study, the combined-event rate declined about 3% per year in all five
      cities. However, during the first 7-year period (1979-1985), no significant
      trends were found in any of the cities; during the late period (1986-1992),
      significant downward trends were found in all except one city. The change in
      trends between periods was slightly but not significantly greater in the
      treatment cities. It is most likely that some influence affecting all cities, not
      the intervention, accounted for the observed change.

PMID- 10968377
TI  - Associations of weight change and weight variability with cardiovascular and all
      cause mortality in the Chicago Western Electric Company Study.
AB  - Few studies of associations between weight loss or weight fluctuations and
      mortality have been sufficiently long term to permit exclusion of early deaths
      for a portion of follow-up long enough to eliminate likely effects of illness
      related weight loss. This study examined associations of the variation (standard
      deviation and standard deviation about the trend (slope)) and trend (weight loss
      or weight gain) in body mass index (weight (kg)/height (m2) between 1958 and 1966
      (minimum of five measurements) with subsequent 25-year mortality among 1,281 men
      originally aged 40-56 years from the Chicago Western Electric Company Study. In
      multivariate Cox regression models that included two slope variables representing
      weight loss and weight gain and each variability measure separately, weight loss
      and weight gain were significantly related to 15-year mortality but weight
      variability was not. Relative risks for cardiovascular disease mortality were
      1.25 (95% confidence interval (CI): 1.09, 1.45) and 1.14 (95% CI: 0.97, 1.33),
      respectively, for weight loss and weight gain slopes larger by 0.12 kg/m2 per
      year; corresponding relative risks for all-cause mortality were 1.23 (95% CI:
      1.10, 1.38) and 1.15 (95% CI: 1.03, 1.29), respectively. For follow-up years 16
      25, none of these weight variables were significantly related to mortality. These
      results indicate that an association between weight loss and mortality may not
      persist beyond 15 years, and that weight variability may not be related to
      mortality independently of weight loss or weight gain.

PMID- 10968378
TI  - Occupational status, educational level, and the prevalence of carotid
      atherosclerosis in a general population sample of middle-aged Swedish men and
      women: results from the Malmo Diet and Cancer Study.
AB  - The associations among educational level, occupational status, and
      atherosclerosis were investigated during 1992-1994 in a general population sample
      of 4,176 Swedish men and women. Carotid artery intima-media thickness (IMT) and
      carotid stenosis were determined by B-mode ultrasound. Socioeconomic differences
      in mean carotid IMT and odds ratios for carotid stenosis prevalence were
      estimated. In women, the associations among educational level, occupational
      status, and IMT were weak. In men, there was no association between education and
      IMT, while low occupational status was associated with a thicker IMT. Women with
      low education had an increased odds of carotid stenosis compared with women with
      high education (odds ratio (OR) = 2.04, 95% confidence interval (CI): 1.53,
      2.73), while this pattern was weaker among men. Women in manual occupations had
      an increased odds of carotid stenosis compared with women in high- or medium
      level nonmanual occupations (OR = 1.75, 95% CI: 1.29, 2.36), which could not be
      seen among men. After adjustment for risk factors, the association between IMT
      and occupational status in men disappeared, while the associations among
      educational level, occupational status, and carotid stenosis in women persisted.
      The results imply that the atherosclerotic process is associated with
      socioeconomic status in both sexes, and they also indicate the possibility of sex
      differences in the mechanisms connecting socioeconomic status to atherosclerosis.

PMID- 10968379
TI  - Why do Mexican Americans give birth to few low-birth-weight infants?
AB  - There are relatively few low-weight births among Mexican Americans, despite their
      socioeconomic disadvantages. Fewer low-birth-weight (LBW) births result when
      babies are heavier at term or when there are fewer preterm deliveries. The
      authors used 1994 US singleton livebirth birth certificates to compare Mexican
      Americans with non-Hispanic Whites. They found that the lower LBW rate among
      Mexican Americans (5.8%) compared with non-Hispanic Whites (6.1%) occurred
      because fewer small, preterm babies were born to Mexican Americans (3.4% vs.
      3.9%). This result was obscured by two findings. First, the mean birth weight of
      Mexican American babies (3,343 g) was lower than that of non-Hispanic White
      babies (3,393 g). This finding again showed the independence of mean birth weight
      and LBW. Second, the overall preterm birth rate was higher among Mexican
      Americans (10.6%) than non-Hispanic Whites (9.3%). Our hypothesis is that this
      finding reflects errors in recorded gestational age, as illustrated by a strongly
      bimodal birth-weight distribution at young gestational ages for Mexican
      Americans. Further studies on the LBW paradox among Mexican Americans should thus
      focus on gestational age more than on birth weight.

PMID- 10968380
TI  - Community-based study of the transition to adulthood for adolescents with
      psychiatric disorder.
AB  - This longitudinal study examines the transition to adulthood in a randomly
      sampled, community-based cohort of adolescents. The study compares young adult
      outcomes of 33 adolescents with and 148 adolescents without psychiatric disorder.
      After adjustment for differences in age, gender, and social class, adolescents
      with psychiatric disorder were 13.74 times less likely to complete secondary
      school (95% confidence interval (CI): 4.17, 45.17), 4.07 times less likely to be
      employed or in college or trade school (95% CI: 1.4, 12.3), 3.13 times more
      likely to be involved in criminal activity (95% CI: 1.11, 8.87), and 6.46 times
      more likely to have gotten pregnant themselves or to have gotten someone else
      pregnant (95% CI: 1.75, 23.87). While adolescents with psychiatric disorder in
      this community-based study had outcomes that were somewhat more favorable than
      those of adolescents with psychiatric disorder in prior treatment-based studies,
      they nonetheless are at high risk of failing to meet young adult role
      expectations.

PMID- 10968381
TI  - Breast cancer, lactation history, and serum organochlorines.
AB  - The authors analyzed the relation between lactation history, organochlorine serum
      levels-in particular, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and 1,1
      dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE)-and the risk of breast cancer
      within a subsampe from a larger breast cancer case-control study conducted among
      women living in Mexico City, Mexico, between 1990 and 1995. From the original
      study, they selected a random sample of 260 subjects (1:1 case/control ratio).
      Analysis was restricted to 120 cases and 126 controls who had given birth to at
      least one child and had complete information on all key variables. Serum DDE
      levels were higher among cases (mean = 3.84 microg/g lipids, standard deviation =
      5.98) than among controls (mean = 2.51 microg/g lipids, standard deviation =
      1.97). After adjustment for age, age at menarche, duration of lactation, Quetelet
      index, and serum DDT levels, serum DDE levels were positively related to the risk
      of breast cancer (adjusted odds ratio (OR)Q1-Q2 = 1.24, 95% confidence interval
      (CI): 0.50, 3.06; ORQ1-Q3 = 2.31, 95% CI: 0.92, 5.86; ORQ1-Q4 = 3.81, 95% CI:
      1.14, 12.80; test of trend, p = 0.02). The increased risk associated with higher
      serum DDE levels was more apparent among postmenopausal women (ORQ1-Q4 = 5.26,
      95% CI: 0.80, 34.30; test of trend p = 0.03). A longer period of lactation was
      associated with a slightly decreased risk of breast cancer independently of serum
      DDE levels (OR = 0.91, 95% CI: 0.85, 0.99 change in risk per 10 months of
      lactation). Serum DDT level was not related to the risk of breast cancer. The
      data suggest that high levels of exposure to DDE may increase women's risk of
      breast cancer, particularly among postmenopausal women.

PMID- 10968382
TI  - Current medicolegal and confidentiality issues in large, multicenter research
      programs.
AB  - The convenience of fast computers and the Internet have encouraged large
      collaborative research efforts by allowing transfers of data from multiple sites
      to a single data repository; however, standards for managing data security are
      needed to protect the confidentiality of participants. Through Dartmouth Medical
      School, in 1996-1998, the authors conducted a medicolegal analysis of federal
      laws, state statutes, and institutional policies in eight states and three
      different types of health care settings, which are part of a breast cancer
      surveillance consortium contributing data electronically to a centralized data
      repository. They learned that a variety of state and federal laws are available
      to protect confidentiality of professional and lay research participants. The
      strongest protection available is the Federal Certificate of Confidentiality,
      which supersedes state statutory protection, has been tested in court, and
      extends protection from forced disclosure (in litigation) to health care
      providers as well as patients. This paper describes the careful planning
      necessary to ensure adequate legal protection and data security, which must
      include a comprehensive understanding of state and federal protections applicable
      to medical research. Researchers must also develop rules or guidelines to ensure
      appropriate collection, use, and sharing of data. Finally, systems for the
      storage of both paper and electronic records must be as secure as possible.

PMID- 10968383
TI  - Factor analysis of self-reported symptoms: does it identify a Gulf War syndrome?
AB  - Active duty US Naval mobile construction battalion personnel (Seabees) were
      surveyed in 1994 for the presence of a variety of symptoms. Questions were drawn
      from the Hopkins Symptom Checklist and from a collection of symptoms either
      defining clinical depression or commonly reported by Persian Gulf War veterans.
      Of those surveyed, 524 were Gulf War veterans and 935 were nondeployed Gulf War
      era veterans. Factor analysis applied to Gulf War veterans yielded five factors,
      three deriving from the Hopkins Symptom Checklist, one suggesting clinical
      depression, and one containing symptoms commonly reported by Gulf War veterans.
      Factor analysis applied to nondeployed veterans yielded five similar factors.
      Three of the factors yielded statistically significantly greater standardized
      factor scores for Gulf War veterans than for nondeployed veterans. Four of the
      factors resembled factors resulting from a previous analysis on a sample of
      similar Gulf War veterans. Gulf War veterans and nondeployed era veterans
      reported similar clusters of symptoms and illnesses. However, Gulf War veterans
      reported these same clusters with greater frequencies than did nondeployed
      veterans. The authors conclude that, in contrast to a previous report, factor
      analysis did not identify a unique Gulf War syndrome.

PMID- 10968384
TI  - Incidence of influenza-like illness, measured by a general practitioner sentinel
      system, is associated with day-to-day variations in respiratory health in panel
      studies.
AB  - During three consecutive winters beginning in 1992-1993, the association between
      the incidence of influenza and influenza-like illness (ILI), measured by a
      general practitioner sentinel system, and respiratory health was investigated in
      an air pollution panel study. Data from 22 panels of children (7-11 years old)
      and adults (50-70 years old) in the Netherlands were used. ILI incidence was
      associated with peak expiratory flow, respiratory symptoms, and bronchodilator
      use. Peak ILI incidence of 122 cases/10,000 subjects was associated with a
      decrement in peak expiratory flow of 6% and a 3- to 4.5-fold increase in symptom
      reporting and bronchodilator use. In panel studies, ILI incidence might be used
      to adjust for confounding by acute respiratory infections.

PMID- 10968385
TI  - Re: "Presenting statistical uncertainty in trends and dose-response relations".

PMID- 10968386
TI  - Re: "Health problems in teenage daily smokers versus nonsmokers, Norway, 1995
      1997: the Nord-Trondelag Health Study".

PMID- 10968387
TI  - Galileo's peers.

PMID- 10968388
TI  - Tubulointerstitial nephritis following high-dose ifosfamide in three breast
      cancer patients.
AB  - We report three cases of women with breast cancer who developed renal impairment
      following treatment with high-dose ifosfamide. All the women underwent renal
      biopsy, which demonstrated severe interstitial damage with tubular changes by
      light and electron microscopy. Although reversible acute tubular dysfunction is
      well recognised with ifosfamide therapy, the long-term outcome of ifosfamide
      induced renal injury remains unclear. The results of the current study suggest
      that ifosfamide can cause severe irreversible renal tubulointerstitial injury and
      should be used with caution even when there is initially normal renal function.

PMID- 10968389
TI  - The initiation of intimal thickening in human arteries.
AB  - To obtain more detailed information about the relationship of intimal thickening
      to defects in the elastin structure of the arterial wall, the internal elastic
      lamina and subsequent elastin formation in the intima was studied by very oblique
      sectioning of paraffin sections of the arterial wall, and by scanning electron
      microscopy of formic acid digested preparations. Comparison was made in the same
      subject between the internal thoracic artery (a vessel showing only slight
      intimal thickening) and the anterior descending coronary (which usually develops
      advanced intimal thickening). There was no evidence of penetration of the normal
      fenestrations of the internal elastic lamina by medial smooth muscle cells. This
      took place through major defects of this lamina and resulted in a change from
      transverse to longitudinal orientation of these cells and the accompanying
      elastin fibers of the intima. A further condensation of elastin (greater for the
      internal thoracic) occurred in the intima subjacent to the endothelial cells.

PMID- 10968390
TI  - Histological assessment of apoptotic cell death in cardiomyopathies.
AB  - Apoptosis in the myocardium is complex and often difficult to recognise. Myocyte
      apoptosis is scattered across the myocardial wall and is restricted to individual
      cells. In the present study, we describe the amount of apoptosis in 50
      endomyocardial biopsies taken from 50 patients with dilated cardiomyopathy, in 14
      hearts with hypertrophic cardiomyopathy and in five hearts with arrhythmogenic
      dysplasia of the right ventricle. As a control group, 15 endomyocardial biopsies
      from 15 transplanted hearts (of live patients) were used. Apoptosis was
      immunohistochemically determined in paraffin sections with the TUNEL method. In
      each specimen the TUNEL index was calculated as the percentage of TUNEL-positive
      nuclei among a total number of 200 counted nuclei. Cellular morphology was
      assessed in conjunction with TUNEL staining. The mean percentage of TUNEL
      positive myocardial cells varied from 4% for dilated cardiomyopathy to 17.5% for
      arrhythmogenic right ventricle dysplasia and 18.5% for hypertrophic
      cardiomyopathy, whereas no signs of apoptotic myocardial cell death were found in
      normal subjects. The numbers of apoptotic cells in dilated cardiomyopathy
      specimens were significantly lower by comparison with both those of hypertrophic
      cardiomyopathy and those of arrhythmogenic right ventricular dysplasia specimens.
      It is evident that apoptosis constitutes a major biological phenomenon in the
      development of at least some heart diseases, but its role in their
      pathophysiology has yet to be delineated.

PMID- 10968391
TI  - The measurement of IgA and IgG transglutaminase antibodies in celiac disease: a
      comparison with current diagnostic methods.
AB  - Celiac disease (CD) is an inflammatory disorder of the small intestine induced by
      cereal prolamins. The demonstration of IgA endomysial antibodies (EMA) is
      currently the most reliable serological screen for CD. The antigenic target is
      transglutaminase. The aim of this study was to develop an ELISA assay for the
      detection of antibodies to transglutaminase (TGA), and to assess the sensitivity
      and specificity of TGA for the detection of celiac disease against the benchmarks
      of jejunal biopsy, antigliadin antibodies (AGA) and EMA. Sera from 57 patients
      with celiac disease were tested for IgA and IgG TGA, IgA EMA, IgA and IgG AGA,
      and the total IgA level. The sensitivity, specificity, predictive value and
      concordance of AGA, EMA and TGA were assessed against the gold-standard biopsy
      result. IgG plus IgA TGA offered 100% sensitivity in CD patients for whom no
      dietary intervention had been commenced, with a specificity of 61%. The
      sensitivity of TGA dropped from 100 to 79% after dietary restriction. In patients
      on no gluten restriction, there was 100% agreement between TGA and EMA, and 100%
      agreement between TGA and AGA for the IgA isotype. The false-positive rate for
      TGA was 53% in Down's syndrome patients and 25% in patients with systemic
      autoimmune disorders. We conclude that testing for TGA is a reliable diagnostic
      serology for celiac disease, with improved sensitivity compared with established
      methods. The results suggest that serial TGA measurements may be a more and
      accurate marker for dietary compliance than AGA, but prospective studies are
      required.

PMID- 10968392
TI  - The tunel assay in the diagnosis of graft-versus-host disease: caveats for
      interpretation.
AB  - Acute graft-versus-host disease (GVHD) is a significant cause of morbidity and
      mortality following bone marrow transplantation, and early detection is important
      to allow effective therapy. Since the presence of apoptotic keratinocytes
      (dyskeratotic bodies) has been suggested as a useful diagnostic criterion for
      GVHD, attention has focused on the use of the TUNEL assay to detect apoptosis in
      clinical specimens. We reviewed clinical specimens upon which TUNEL had been
      performed for possible artifacts that might interfere with accurate evaluation
      for GVHD. Several distinct types of artifact were found and could be re-created
      in experimental systems. Artifacts in TUNEL staining generally resulted from the
      lack of specificity of this reaction for apoptotic cell death. Artifacts were
      found resulting from inadequate fixation, over-exposure of the TUNEL reaction,
      and proximity to the section edge. In addition, a novel artifact, apparently
      resulting from DNA shearing during the sectioning process, was noted and
      confirmed using confocal microscopy of experimental specimens. The TUNEL assay
      must therefore must be interpreted with caution in the clinical setting. In our
      laboratory, we consider TUNEL-positive cells as apoptotic only when accompanied
      by apoptotic morphology. Although these criteria clearly miss some cells in the
      early stages of apoptosis, they provide the highest specificity for apoptotic
      cell death.

PMID- 10968393
TI  - Broadsheet number 57: problems in fine needle biopsy of the thyroid.
AB  - The role of fine needle biopsy and cytological diagnosis in the preoperative
      evaluation of thyroid nodules is reviewed on the basis of the current literature
      as well as the authors' personal experience. Technical aspects and guidelines for
      reporting thyroid samples are discussed in some detail. The main emphasis is on
      diagnostic pitfalls, those which may lead to a false-negative diagnosis, to a
      false-positive diagnosis or to an erroneous typing of the lesion, and their
      cytological patterns are described.

PMID- 10968394
TI  - Test and teach. Number One hundred and two. Vascular transformation of lymph node
      sinuses.

PMID- 10968395
TI  - Test and teach. Number One hundred and three. Plexiform fibrohistiocytic tumor.

PMID- 10968396
TI  - Test and teach. Number One hundred and four. Mu heavy chain disease (mu-HCD).

PMID- 10968398
TI  - Combined large cell neuroendocrine, small cell and squamous carcinomas of the
      lung with rhabdoid cells.
AB  - Two unusual cases of combined lung carcinoma are presented. Both patients, aged
      50 and 53 years, had strong histories of cigarette smoking and presented with
      lung masses. Microscopic examination revealed an uncommon combination of primary
      lung cancers. Both cases had a dominant histological picture of large cell
      neuroendocrine carcinoma. The first case was combined with both squamous and
      small cell carcinomas in almost equal proportions, while the second consisted of
      large cell neuroendocrine and squamous carcinomas with a focal area of small cell
      carcinoma. In addition, both cases contained rhabdoid cells. One of the cases
      pursued an aggressive clinical course with death in 6 months. The other patient
      presented with recurrent tumor 12 months after the operation and died shortly
      thereafter. These cases illustrate two examples of uncommon combined lung
      cancers: large cell neuroendocrine carcinoma combined with squamous carcinoma and
      small cell carcinoma. An additional feature was the presence of rhabdoid cells in
      both cases. It is felt that the rhabdoid component is a reflection of de
      differentiation or poor differentiation, and may contribute to the aggressive
      nature of both tumors.

PMID- 10968397
TI  - Identification of multiple genital HPV types and sequence variants by consensus
      and nested type-specific PCR coupled with cycle sequencing.
AB  - Consensus and type-specific HPV primers were employed for PCR and cycle
      sequencing of genital HPVs in scrapings and colposcopically directed biopsies of
      the cervix from a cohort of 188 female sex workers. A total of 27 individuals
      tested positive for a broad spectrum of HPV types, including HPVs 6b, 16, 18, 31,
      33, 34, 35, 45, 56 and 58, as well as a new HPV type, with seven individuals
      displaying dual infections. Good correlation between the results of individually
      paired samples was observed. A HPV 16 primer biotinylated at the 5' end was also
      used as a probe, which could successfully detect amplified products of HPV 16 but
      not other HPV types tested by an automated ELISA detection system. DNA sequence
      analysis revealed several HPV sequence variants that harbored mutations,
      especially in the E6 gene, many of which culminated in non-conservative amino
      acid substitutions in the transforming E6 oncoprotein. Such an approach of
      coupling PCR with cycle sequencing permits the determination of many known and
      even novel HPV types associated with varying degrees of risk to cervical
      carcinogenesis, and enables the identification of HPV sequence variants of
      putative biological and clinical significance, thus justifying its utility as an
      adjunct tool to complement cervical cytology and colposcopy. This study also
      emphasises the need for educational, interventional and behavioral modification
      to minimise HPV transmission, such as through consistent condom usage among sex
      workers.

PMID- 10968399
TI  - Cytodiagnosis of tuberculosis of the skull by fine needle aspiration cytology: a
      case report.
AB  - Close to one-third of the world's population is believed to be infected with
      tuberculosis, with the vast majority being in the developing world. However, even
      in the developed world, the incidence of this disease has been steadily
      increasing. Tuberculosis is very common in the Indian subcontinent, but at the
      same time tuberculous infection of the skull is rare and very few cases have been
      reported. We report a child who presented with a swelling of the frontal bone of
      the skull. Fine needle aspiration yielded the cytological diagnosis of
      tuberculosis on the basis of a necrotising granulomatous process with acid-fast
      bacilli detected on Ziehl Neelsen stain. This procedure obviated the need for an
      operative procedure and the patient responded to anti-tuberculous therapy. As the
      incidence of tuberculous infection is on the increase, both in the developed and
      in the developing world, the importance of diagnosis by newer non-invasive
      techniques like fine needle aspiration cytology cannot be overemphasized. To the
      best of our knowledge, this is the first report of its kind in the world
      literature.

PMID- 10968400
TI  - Papillary cystic tumor of the pancreas coexisting with hairy cell leukemia.
AB  - The coexistence of a pancreatic papillary cystic tumor with hairy cell leukemia
      is reported. To the best of our knowledge this association has never been
      published. A 41-year-old man diagnosed with hairy cell leukemia developed a
      second malignancy that corresponded to a papillary cystic pancreatic tumor. The
      patient underwent splenectomy and a tumoral surgical resection, and is currently
      well at 21 months follow-up. A pathogenetic relationship between the two
      malignancies was not demonstrated. Hairy cell leukemia has been reported to be
      associated to a great number of different second malignancies. In contrast, only
      two papillary cystic tumors of the pancreas have been described associated to a
      second neoplasm, a papillary thyroid carcinoma and a colonic carcinoma. This
      unusual benign or low-grade malignant pancreatic tumor more commonly occurs in
      the tail of the pancreas of young women. We want to stress the unusual
      presentation of this pancreatic tumor affecting the head of the gland in a male
      patient as well as its coexistence with a hairy cell leukemia.

PMID- 10968401
TI  - Uterine hemorrhage in a menopausal female associated with an arteriovenous
      malformation and myometritis.
AB  - A case is described of vaginal bleeding in a 67-year-old female as the first
      manifestation of a uterine arteriovenous malformation (AVM). Although bleeding is
      the commonest presentation of an AVM, this is the first case known to have been
      precipitated by florid myometritis associated with the long-standing presence of
      an intra-uterine contraceptive device (IUCD). Uterine imaging studies utilising
      ultrasound scan with color Doppler were instrumental in suggesting the source of
      bleeding in this case. Subsequently, the patient suffered a torrential hemorrhage
      which necessitated hysterectomy.

PMID- 10968402
TI  - Occasional comment: pathology in Madagascar.

PMID- 10968403
TI  - The biology of ophiobolins.
AB  - This review article aims at summarizing the research findings on the biological
      aspects of ophiobolins, phytotoxins produced by the pathogenic fungi Bipolaris
      species, which usually infect rice, maize and sorghum. The topics covered include
      the organisms that produce the various ophiobolins, the structural variations of
      ophiobolins, the biological actions of ophiobolins in plants, animals and
      microorganisms, and the mode of action and the possible use of ophiobolin A as a
      calmodulin antagonist.

PMID- 10968404
TI  - Steroid hormone-induced effects on membrane fluidity and their potential roles in
      non-genomic mechanisms.
AB  - Steroid hormones are lipophilic suggesting they intercalate into the bilayer of
      target cell plasma membranes, potentially altering the fluidity and function of
      the membrane. The present study measured the effects of steroidal exposure on
      both phospholipid fluidity and integral protein mobility. Studies were performed
      on the effects of a variety of steroids on phosphatidylcholine liposomes,
      synaptosomal plasma membranes and sarcoplasmic reticulum membranes. Progesterone
      decreased the lipid fluidity, whereas testosterone had no effect on lipid
      movement. The estrogen, 17 beta-estradiol, an aromatised metabolite of
      testosterone, increased lipid mobility. In each case, the steroid action was
      concentration-dependent. The steroids all increased the activity of the Ca2+
      ATPase of SR membrane, in keeping with their effects on this enzyme's aggregation
      state. The results suggest that, although lipid fluidity is a factor influencing
      protein activity, their mobility within the bilayer is the primary determinant of
      enzyme activity in the membrane for most proteins.

PMID- 10968405
TI  - Pyronaridine: an effective antimalarial against multidrug-resistant malaria.
AB  - Pyronaridine, administered intramuscularly (im) to Swiss mice infected with the
      lethal multidrug-resistant Plasmodium yoelii nigeriensis, was found to exert high
      blood schizontocidal activity. The efficacy of doses of pyronaridine ranging from
      0.625 to 30 mg (base/kg) was evaluated using a 4 day treatment schedule (drug was
      administered at 0, 24, 48 and 72 hrs). It was found that doses of 2.5mg/ kg and
      higher protected animals completely from the lethal effects of the parasite. The
      same degree of protection was found when the treatment duration was reduced to 3
      days. This study shows that pyronaridine is a potentially useful antimalarial
      drug that could be exploited for the control of multidrug-resistant malaria
      infection.

PMID- 10968406
TI  - Sexual hormones terminate in the rat: the significantly enhanced
      catecholaminergic/serotoninergic tone in the brain characteristic to the post
      weaning period.
AB  - The amount of dopamine released from the striatum, substantia nigra and
      tuberculum olfactorium, noradrenaline from locus coeruleus and serotonin from the
      raphe, was significantly higher in four and five weeks old rats than in three
      month old ones, proving that the catecholaminergic/serotoninergic activity
      enhancer (CAE/SAE) regulation works unrestrained during developmental longevity
      and is restricted thereafter. As the dampening of the CAE/SAE regulation (end to
      the second month of age) coincided temporally with the appearance of sexual
      hormones, we castrated three weeks old male and female rats and measured at the
      end of the third month of their life the release of catecholamines and serotonin
      from selected discrete brain regions. The amount of catecholamines and serotonin
      released from the neurons was significantly higher in castrated than in untreated
      or sham operated rats, signalting that sexual hormones inhibit the CAE/SAE
      regulation in the brain. We therefore treated male and female rats s.c. with oil
      (0.1 ml/rat), testosterone, (0.1 mg/rat), estrone (0.01 mg/rat) and progesterone
      (0.5 mg/rat), respectively, and measured their effect on the CAE/SAE regulation.
      Twenty-four hours after a single injection with the hormones, the release of
      noradrenaline, dopamine and serotonin was significantly inhibited in the
      testosterone or estrone treated rats, but remained unchanged after progesteron
      treatment. In rats treated with a single hormone injection, testosterone in the
      male and estrone in the female was the significantly more effective inhibitor.
      Remarkably, the reverse order of potency was found in rats treated with daily
      hormone injections for 7 or 14 days. After two-week treatment with the hormones
      estrone was in the male and testosterone in the female the significantly more
      potent inhibitor of the CAE/SAE regulation. The data indicate that sexual
      hormones terminate the hyperactive phase of adolescence by dampening the impulse
      propagation mediated release of catecholamines and serotonin in the brain.

PMID- 10968407
TI  - Sativin: a novel antifungal miraculin-like protein isolated from legumes of the
      sugar snap Pisum sativum var. macrocarpon.
AB  - An antifungal protein designated sativin was isolated from the legumes of the
      sugar snap (also known as honey pea) Pisum sativum var. macrocarpon. The
      procedure entailed extraction, affinity chromatography on Affi-gel blue gel and
      ion exchange chromatography on CM-Sepharose. The protein exhibited a molecular
      weight of 38 kDa in SDS-polyacrylamide gel electrophoresis. It possessed an N
      terminal amino acid sequence which showed similarity to those of miraculin (a
      sweet protein) and pisavin (a ribosome-inactivating protein from Pisum sativum
      var arvense Poir manifesting similarity to miraculin). Unlike pisavin, however,
      sativin demonstrated negligible ribonuclease activity and inhibited translation
      in a rabbit reticulocyte lysate system with a very low potency (IC50= 14 microM).
      Sativin exerted antifungal activity against Fusarium oxysporum, Coprinus comatus
      and Pleurotus ostreatus but not against Rhizoctonia solani.

PMID- 10968408
TI  - Differential effects of N-methyl-D-aspartate receptor stimulation on growth
      hormone secretion at specific stages of postnatal development of the male rhesus
      monkey.
AB  - The present study attempts to examine the role of N-methyl-D-aspartate (NMDA)
      receptor in the central regulation of growth hormone (GH) secretion during
      specific stages of pubertal development of the male rhesus monkey (Macaca
      mulatta). Infantile (n=4), prepubertal (n=5), peripubertal (n=5) and adult (n=5)
      intact male rhesus monkeys were given an agonist of NMDA receptor, N-methyl-D,L
      aspartate (NMA) (15 mg/kg BW) through a teflon cannula implanted in the saphenous
      vein. Blood samples were collected 20-60 min before and 40-80 min after the
      injection of the drug at 10-20 min intervals. NMA was dissolved in normal saline
      immediately before use and passed through a 0.22 microm filter at the time of
      injection. All bleedings were carried out under ketamine hydrochloride anesthesia
      (initial dose 5 mg/kg BW, im followed by 2.5 mg/kg at 30 min intervals). The
      plasma levels of GH and testosterone (T) were determined by using specific assay
      systems. The hypothalamic-somatotrope activity under basal conditions was studied
      by averaging all the GH concentrations obtained before NMA injection, whereas the
      sensitivity of NMDA receptor to NMA stimulation was determined by comparing basal
      GH levels immediately before NMA injection at 0 min and GH concentrations
      obtained 10 min after the injection. The mean basal plasma concentrations of GH
      in the four groups of animals showed marked age-related differences. The levels
      of GH were found to be higher in infantile and peripubertal monkeys as compared
      to those of prepubertal and adult animals. A single iv injection of NMA produced
      differential effects on GH secretion during specific stages of postnatal
      development depending upon the level of GH secretion under basal conditions.
      Whereas NMA had no demonstrable effect on GH secretion in infantile and
      peripubertal animals in which the basal GH levels were high, it produced
      pronounced effects on GH secretion in prepubertal and adult monkeys wherein
      baseline GH concentrations were low. In conclusion, the present study suggests
      that the glutamatergic component of the control system that governs GH secretion
      by utilizing NMDA receptor may participate in regulation of age-related changes
      in the secretion of GH in the male rhesus monkey.

PMID- 10968409
TI  - Dietary serotonin and alcohol combined may provoke adverse physiological symptoms
      due to 5-hydroxytryptophol.
AB  - The urinary excretion products of serotonin (5-hydroxytryptamine, 5HT) are 5
      hydroxyindole-3-acetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL), and the
      ratio of 5HTOL to 5HIAA is normally very low (< 0.01 ) in man. Intake of foods
      rich in 5HT (high amounts in banana, pineapple, and walnuts) induces a general
      increase in the output of 5HT metabolites, without affecting the 5HTOL/5HIAA
      ratio. In contrast, during metabolism of ethanol there is a shift in the
      catabolic pattern of 5HT, and the formation of 5HTOL increases appreciably at the
      expense of 5HIAA. Accordingly, the urinary 5HTOL/ 5HIAA ratio increases and does
      not recover to baseline levels until several hours after ethanol has been cleared
      from the body. When 10 healthy subjects ingested a moderate dose of ethanol (0.5
      g/kg), the urinary 5HTOL/SHIAA ratio was increased approximately 70-fold on
      average at 4 h after intake. When the same amount of ethanol was ingested
      together with 3 bananas (approximately 10 mg 5HT), this ratio was increased
      approximately 100-fold at 4 h and still significantly higher than baseline levels
      at 24 h. Starting at 3-4 h after the combined intake of ethanol and banana, 7
      subjects experienced one or more unpleasant symptoms (diarrhea, headache, and
      fatigue) which are associated with the 5HT system. The events were transient but
      typically lasted for several hours, and the duration correlated with the time
      period during which 5HTOL levels were raised. Intake of ethanol and banana
      separately produced much lower increases in 5HTOL output and caused no
      corresponding effects. This observation indicate that dietary 5HT intake together
      with even a moderate dose of ethanol can provoke unpleasant physiological
      symptoms. The symptoms may be attributed to the high concentration of 5HTOL.

PMID- 10968410
TI  - Morphological and functional changes of rabbit mesenteric artery cultured with
      fetal bovine serum.
AB  - The aim of this study was to examine the morphological and functional changes in
      rabbit mesenteric arterial tissue cultured with fetal bovine serum. In the
      endothelium-denuded arteries cultured under a serum-free condition for one week
      (serum-free arteries), morphology of the smooth muscle layer was intact. In the
      serum-free arteries, high K+ -induced contraction did not change but
      norepinephrine-induced contraction slightly decreased compared with that in the
      freshly isolated arteries, whereas the sensitivity to these stimulants was
      significantly augmented. In the medial layer of the arteries cultured with 10%
      fetal bovine serum for one week (serum-treated arteries), proliferation,
      disorientation and death of smooth muscle cells were observed. In the serum
      treated arteries, both the amplitude of contractions induced by high K+ and
      norepinephrine and the sensitivity to these stimulants were significantly reduced
      compared with those of the serum-free arteries. The reduced norepinephrine
      induced contraction in the serum-treated arteries was partially recovered by
      adding NG-monomethyl-L-arginine (L-NMMA), a nitric oxide (NO) synthase inhibitor,
      to the assay medium. In alpha-toxin permeabilized arteries, the amplitude of Ca2+
      -induced contraction and the sensitivity of the contractile apparatus to Ca2+
      were significantly reduced after serum-treatment. These results suggest that
      chronic serum-treatment of rabbit mesenteric arteries impairs muscle
      contractility by the morphological and phenotypic changes in smooth muscle cells.
      NO production in smooth muscle cells is also responsible for the decreased
      contractility after the serum-treatment.

PMID- 10968411
TI  - Pyruvate dehydrogenase activity and energy metabolite levels following bilateral
      common carotid artery occlusion in rat brain.
AB  - The influence of chronic cerebral hypoperfusion on cerebral energy metabolism was
      studied. The bilateral common carotid arteries of Wistar rats were occluded for
      0, 2, 7, and 28 days. Cerebral energy metabolism was evaluated by assaying
      adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels and
      measuring pyruvate dehydrogenase (PDH) activity (each time point, n = 6).
      Pathological changes were assessed light-microscopically by Kluver-Barrera
      staining and immunohistochemical labeling for astroglia (each time point, n = 3).
      There were no changes in ATP and PCr levels or PDH activity; there was slight but
      significant transient lactate accumulation at 2 days. Myelin pallor and increase
      in immuno-reactive astroglia were only observed at 28 days. These results
      indicate that chronic cerebral hypoperfusion induces delayed white matter changes
      in the corpus callosum of rat brain, but does not affect energy production.

PMID- 10968412
TI  - Overexpression of phospholipase Cbeta-1 protects NIH3T3 cells from oxidative
      stress-induced cell death.
AB  - Oxidative stress has been implicated in a wide range of cellular damage which
      includes DNA oxidation, membrane lipid peroxidation, and apoptosis. In our study,
      we found that overexpression of PLC-beta1 in NIH3T3 fibroblasts protected them
      from cell death occuring in response to oxidative stress. Cell death caused by
      treatment with prooxidant tert-butylhydroperoxide (TBH), H2O2, or CdCl2 was
      considerably suppressed in PLC-beta1 overexpressed NIH/beta1-14 cells in
      comparison to control NIH/neo cells. However, overexpression of PLC-beta1 failed
      to protect the cells from toxicity by diamide or KCN. In addition, while
      accumulation of c-fos mRNA was observed within 30 min of TBH treatment in vector
      transfected NIH/neo cells, TBH-induced c-fos mRNA generation was completely
      suppressed in NIH/beta1-14 cells, while that of c-jun and GAPDH was not affected.
      These findings suggest that PLC-beta1 may play a role in process that can protect
      cells from oxidative stress-induced cell death.

PMID- 10968413
TI  - The effect of aspirin and two nitric oxide donors on the infarcted heart in situ.
AB  - Nitric oxide (NO) donors are heterogeneous substances which release NO, a
      biologically active compound. NO released by nitric oxide donors has important
      effects on the circulation by causing vasodilation, diminishing myocardial
      contractile force, inhibiting platelet aggregation, and counteracting the effects
      of thromboxane A2. In the infarcted heart, activation of the inducible form of
      nitric oxide synthase (iNOS) and the formation of prostacyclin and thromboxane A2
      by cyclooxygenase (COX) were increased. Myocardial infarction also resulted in
      increased myocardial NO production. Aspirin (acetylsalicylic acid. ASA) at low
      concentration (35 mg/kg/day) fails to change iNOS production, in contrast to
      higher dose (150 mg/kg/day) which, as previously shown, inhibits iNOS activity.
      ASA at all doses also suppresses myocardial prostanoid formation because of
      inhibition of COX. Recently, two NO donors have been synthesized: NCX 4016 and
      Diethylenetriamine/NO (DETA/NO). NCX 4016 combines an NO-releasing moiety with a
      carboxylic residue via an esteric bond. We describe here that NCX 4016 (65
      mg/kg/day) increased prostacyclin and thromboxane A2 production in the infarcted
      heart muscle, overcoming the inhibitory effects of ASA. As a result of nitric
      oxide release, oxidation products of NO (NO2- and NO3-; NOx) in arterial blood
      rose following administration of NCX 4016. On oral administration, NCX 4016 did
      not change systemic arterial pressure. The effects of a single NO donor, DETA/NO
      (1.0 mg/kg/day) on the infarcted heart were also investigated On intravenous
      administration, the compound increased NO concentration in arterial blood
      slightly but to a lesser degree than NCX 4016. Like NCX 4016, it raised
      myocardial production of prostacyclin and thromboxane A2 in the infarcted heart.
      However, it caused a severe fall in blood pressure. These findings demonstrate
      that newly-synthesized NO donors release nitric oxide in situ and increase
      myocardial production of prostanoids. NCX 4016 has therapeutic potential because
      it can be orally administered, lacks hypotensive effects, increases blood levels
      of nitric oxide and myocardial prostacyclin production.

PMID- 10968414
TI  - Luteinizing hormone response to controlled-release deslorelin in estradiol
      benzoate primed ovariectomized gilts.
AB  - Development of a controlled release formulation of gonadotropin releasing hormone
      that would stimulate a LH surge capable of reducing the time span of ovulations
      would greatly benefit reproductive management because a single timed insemination
      could be used. A dose-response study was conducted to determine if Deslorelin, a
      potent gonadotropin releasing hormone analogue, delivered via the SABER system, a
      biodegradable controlled release system, would stimulate an ovulatory-like LH
      surge in the pig. Twenty ovariectomized gilts, approximately 200 d old and 100 kg
      body weight (BW), received estradiol benzoate (15 microg/kg BW im) and 48 h
      later, the gilts were given deslorelin at 0, 12.5, 25.0, 50.0 or 100.0 microg im
      (n = 4 each treatment group). Compared to controls, mean blood deslorelin
      concentrations were still elevated at 30 h after deslorelin. Mean deslorelin
      magnitude, area under the curve and duration were sequentially greater (P<0.05)
      in a dose-dependent sequence. Compared to controls, serum LH concentrations were
      elevated (P<0.05) for 6 to 12 h after deslorelin. A dose-response relationship
      was absent for all parameters of LH secretion. Magnitude of the serum LH response
      was greatest (P<0.05) in the 12.5 microg and 50.0 microg groups, whereas area
      under the curve was lower (P<0.05) after 25.0 microg of deslorelin than after
      12.5, 50.0 and 100.0 microg, which were not different from each other. Thus, no
      more than 12.5 microg of deslorelin is necessary to obtain maximum LH release in
      the model studied and doses less than 12.5 microg may also be effective.

PMID- 10968415
TI  - Assessment of equine sperm mitochondrial function using JC-1.
AB  - The fluorescent carbocyanine dye, JC-1, labels mitochondria with high membrane
      potential orange and mitochondria with low membrane potential green. Evaluation
      of mitochondrial membrane potential with JC-1 has been used in a variety of cell
      types, including bull spermatozoa; however, JC-1 staining has not yet been
      reported for equine spermatozoa. The aim of this study was to apply JC-1 staining
      and assessment by flow cytometry or a fluorescence microplate reader for
      evaluation of mitochondrial function of equine spermatozoa. Six ejaculates from
      four stallions were collected and centrifuged through a Percoll gradient (PERC).
      Spermatozoa were resuspended to 25 x 10(6) cells/mL, samples were split, and one
      sample was repeatedly flash frozen (FF) in LN2 and thawed. The following
      gradients of PERC:FF were prepared: 100:0 (100), 75:25(75), 50:50 (50), 25:75
      (25) and 0:100 (0). Samples were stained with 2.0 microM JC-1 and assessed for
      staining by flow cytometry and by a fluorescence microplate reader. A total of
      10,000 gated events was analyzed per sample with flow cytometry. The mean
      percentage of cells staining orange for the 100, 75, 50, 25 and 0 treatments was
      92.5, 72.8, 53.4, 27.3 and 7.3, respectively. The expected percentage of
      spermatozoa forming JC-1 aggregates was correlated with the actual percentage of
      orange labeled sperm cells determined by flow cytometry (r2=0.98). Conversely, JC
      1 monomer formation was negatively correlated with expected mitochondrial
      membrane potential (r2=-0.98). The blank corrected orange fluorescence, assessed
      by microplate assay, was significantly (P<0.0001) correlated with the expected
      (r2=0.49) and with the flow cytometric (r2=0.50) determination of percentage of
      spermatozoa with mitochondria of high membrane potential. Total orange and
      orange:green fluorescence was also correlated with mitochondrial function. These
      results indicate that JC-1 staining can accurately detect changes in
      mitochondrial membrane potential of equine spermatozoa. The relative fluorescence
      of JC-1 labeling patterns of equine spermatozoa can be accurately and objectively
      determined by flow cytometry and by a fluorescence microplate reader assay.

PMID- 10968416
TI  - Effects of the chromatographic fractions of the pig placental trophoblast on
      graft-versus-host reaction.
AB  - The trophoblast has a significant role in regulation of immune reactions at the
      materno-fetal interface by producing biologically active substances. In our
      previous studies five fractions with immunomodulatory activities were isolated by
      gel chromatography from trophoblast of pig placentas. To confirm the
      immunomodulatory effect of these trophoblast fractions on allogeneic in vivo
      systems and to obtain more evidence for the relevance of their activity on the
      maternofetal interface, their effect was studied on graft-versus-host reaction
      (GVHR). To assess the GVHR, the primary and secondary popliteal lymph nodes assay
      was used in mice. In the primary GVHR, 100 microg protein of Fraction 2-5, mixed
      with 5 x 10(6) allogeneic spleen cells (C57BL/6), were injected into one of the
      foot pads of recipient (BALB/c) mice. The secondary GVHR was induced in F1
      (BALB/c x C57BL/6) mice by injection of spleen cells of BALB/c mice
      intraperitoneally preimmunized with allogeneic cells. The GVHR was measured by
      the weight of lymph nodes and by the lymphocyte proliferation. Flow cytometric
      analyses of the cells in the nodes with GVHR and under the influence of Fraction
      4 or 5 were performed using monoclonal antibodies. In the primary GVHR, Fraction
      4 or 5, injected simultaneously with allogeneic spleen cells, significantly
      suppressed the lymph nodes reactivity. Fractions 4 and 5 inhibited the ability of
      the spleen cells of mice intraperitoneally preimmunized with allogeneic cells to
      induce secondary GVHR in F1 mice. The Fraction 2 and 3 had no effect on GVHR. The
      results revealed that a group of proteins with Mr 37-7 kDa, isolated from
      trophoblast of pig placenta, strongly suppressed popliteal lymph node reactivity
      in the primary and secondary GVHR. The data provide convincing evidence for these
      fractions in vivo activity, for their effect across the species barrier and
      suggest the relevance of the same reactions on the materno-fetal interface.

PMID- 10968417
TI  - Reproductive management of silver foxes (Vulpes vulpes) in captivity.
AB  - Specific protocols need to be developed that take into consideration the
      requirements of silver foxes. This study was designed to investigate the
      reproduction of 26 pairs of silver foxes (Vulpes vulpes). Reproduction parameters
      (breeding season, age at puberty, fecundity and fertility) of the foxes were
      examined under experimental conditions, and new techniques to optimize fox
      breeding were assessed. Staining of the vaginal smears with the double Harris
      Schorr stain allowed for the precise detection of estrus and proved to be more
      reliable than simply measuring vaginal resistance. Ultrasonography was
      demonstrated to be useful for pregnancy diagnosis and prediction of parturition.
      Results demonstrate that the methods reported in this paper are easily applicable
      to similar studies carried out on small groups of animals within the framework of
      fox animal experimentation.

PMID- 10968418
TI  - Effect of disease on reproduction in the dairy cow: a meta-analysis.
AB  - Effects on reproduction of dystocia, stillbirth, abortion, milk fever, retained
      placenta, metritis, cystic ovaries, anestrus, ketosis, displaced abomasum,
      locomotor disorders, and mastitis were reviewed. Papers were considered if they
      provided quantitative estimates of diseases on days to first estrus, days to
      first service, conception rate at first service, days from first service to
      conception, days to conception or days open, calving interval, conception rates
      at various days post partum (dpp), and number of services per conception or per
      cow. Only papers in English in peer-reviewed journals were selected for analysis
      of post 1960 data from intensive dairy regions. Seventy papers fulfilled the
      selection criteria. Summary estimates of disease effects were calculated
      according to meta-analysis methods, and study designs were described in detail to
      identify possible heterogeneity of the results. Stillbirth, milk fever, displaced
      abomasum and mastitis had no effect on reproduction. Clinical ketosis, dystocia
      and retained placenta were associated with 2 to 3 more days to first service and
      with a 4 to 10% lower conception rate at first service, resulting in 6 to 12 more
      days to conception. Locomotor disorders were associated with an average increase
      of 12 d to conception, with wide variation depending on lesions and stage of
      occurrence. Metritis was associated with 7 more days to first service, 20% lower
      conception rate at first service, resulting in 19 more days to conception. Cystic
      ovaries were associated with 6 to 11 more days to first service and with 20 to 30
      more days to conception. Anestrus was associated with 26 more days to first
      service and with an 18% lower conception rate at first service, resulting in 41
      more days to conception. Abortion was associated with 70 to 80 more days to
      conception.

PMID- 10968419
TI  - Body dimensions and birth and organ weights of calves derived from in vitro
      produced embryos cultured with or without serum and oviduct epithelium cells.
AB  - Body dimensions, birth and organ weights of calves derived from embryos produced
      in 2 in vitro culture systems (modified SOFaa with 20% cattle serum and co
      cultured with oviduct-epithelium cells [IVPserum, n=8], and modified SOFaa with 3
      mg/mL PVA [IVPdefined, n=6]) were compared with calves originating from
      artificial insemination (AI, n=85). Three additional IVP calves were included
      which had been vitrified as mature oocytes by the open pulled straw (OPS) method,
      warmed, fertilized and cultured to the blastocyst stage in modified SOFaa with 5%
      cattle serum, then again OPS-vitrified and warmed prior to transfer (IVPops,
      n=3). At birth, gestation length and birth weights were registered for all
      calves. At 1 wk of age all 17 IVP and 7 of the AI calves were killed, and their
      body dimensions and organ weights recorded. Birth weight was higher for the
      IVPserum and IVPops calves than for AI control calves (kg +/- SEM: IVPserum
      46.9+/-1.8, IVPops 50.6+/-2.4, AI 41.8+/-0.8; P < 0.002). There was no difference
      between IVP and AI calves regarding gestation length and no effect of culture
      conditions on body dimensions or organ weights, except for longer hind legs in
      IVPdefined calves compared with AI calves (cm +/- SEM: IVPdefined 93+/-2, AI 87+/
      2; P < 0.04). The IVPops calves had an increased liver weight compared with AI
      and the other IVP calves (g +/- SEM: IVPops 1.457+/-59; AI 1,117+/-37; IVPserum
      1,159+/-34, IVPdefined 1,073+/-39; P < 0.0003). It is concluded that in vitro
      culture of bovine embryos in the presence of serum and oviduct epithelium cells
      increased birth weight but not organ weight and body dimension in 1-wk-old
      calves. However, vitrification of the ova as oocyte and again as blastocysts
      increased birth weight and liver size. This possible effect of cryopreservation
      of oocytes on subsequent fetal development awaits further investigation.

PMID- 10968420
TI  - Effect of growth hormone releasing hormone (GHRH) and vasoactive intestinal
      peptide (VIP) on in vitro bovine oocyte maturation.
AB  - The aim of this study was to investigate the effects of growth hormone releasing
      hormone (GHRH) and the structural-related peptide vasoactive intestinal peptide
      (VIP) on nuclear maturation, cortical granule distribution and cumulus expansion
      of bovine oocytes. Bovine cumulus oocyte complexes (COCs) were cultured in M199
      without FCS and gonadotropins and in the presence of either 100 ng/mL bovine GHRH
      or 100 ng/mL porcine VIP. The COCs were incubated at 39 degrees C in a humidified
      atmosphere with 5% CO2 in air, and the nuclear stage was assessed after 16 or 24
      h of incubation using DAPI staining. Cortical granule distribution was assessed
      after 24 h of incubation using FITC-PNA staining. To assess the effects of GHRH
      and VIP on cumulus expansion, COCs were incubated for 24 h under the conditions
      described above. In addition, 0.05 IU/mL recombinant human FSH was added to GHRH
      and VIP groups. Cultures without GHRH/VIP/FSH or with only FSH served as negative
      and positive controls, respectively. At 16 h neither GHRH (42.9%) nor VIP (38.5%)
      influenced the percentage of MII stage oocytes compared with their respective
      controls (44.2 and 40.8%). At 24 h there also was no difference in the percentage
      of MII oocytes between GHRH (77.0%), VIP (75.3%) and their respective controls
      (76.0 and 72%). There was no significant cumulus expansion in the GHRH or VIP
      group, while FSH induced significant cumulus expansion compared with the control
      groups, which were not inhibited by GHRH or VIP. Distribution of cortical
      granules was negatively affected by GHRH and VIP. The percentage of oocytes
      showing more or less evenly dispersed cortical granules in the cortical cytoplasm
      aligning the oolemma (Type 3) was lower in the GHRH (2.7%) and VIP (7.8%) groups
      than in the control group (15.9%). In conclusion, GHRH and VIP have no effect on
      nuclear maturation or cumulus expansion of bovine COCs but retard cytoplasmic
      maturation, as reflected by delayed cortical granule migration.

PMID- 10968421
TI  - Relationship among estradiol, cortisol and intensity of estrous behavior in dairy
      cattle.
AB  - Economic profitability of a dairy farm is based, in part, on the calving interval
      of the cows. The optimal interval is 365 d. To achieve this, the cow needs to be
      pregnant within 85 d post partum. The first and most problematic step in this
      process is the determination of the optimal time for insemination, which is based
      on estrous behavior. The expression of estrous behavior, however, is at a low
      level in modem dairy herds, resulting in low detection rates and longer calving
      intervals. In the present study, a point scale was used to monitor postpartum,
      nonpregnant cows for estrous symptoms. Frequent blood samples were taken around
      estrus, and the cows were fit with pedometers to measure their activity.
      Correlations between the occurrence of symptoms of estrus and levels of estradiol
      and cortisol were then analyzed. Standing heat, the standard symptom of estrus,
      was observed in only 53% of the cows. A high correlation of 0.7 was found between
      estradiol concentration and estrous behavior. This was empasized by the fact that
      the estradiol level reached its highest level of 7.76 + 2.39 (SD) pg/mL at the
      same time as the highest behavior score. The highest pedometer readout lagged 8 h
      behind this moment. Cortisol levels did not exceed the physiological levels in
      rest situations but showed an increase at the time estrous behavior was at its
      maximum. The present study showed that standing heat is not the primary symptom
      for detecting estrus in cows. Pedometers are a useful aid but they have to be
      read several times a day. The high correlation between the visual symptoms of
      estrus and estradiol concentrations indicates that visual estrus detection is an
      efficient, reliable way to determine the right time for insemination.

PMID- 10968422
TI  - Effects of wortmannin on the kinetics of GVBD and the activities of the
      maturation-promoting factor and mitogen-activated protein kinase during bovine
      oocyte maturation in vitro.
AB  - The present study was conducted with the objective of examining the effect of
      wortmanin, a specific PI 3-kinase inhibitor, on the kinetic of GVBD, and on the
      activities of the maturation-promoting factor (MPF) and mitogen-activated protein
      (MAP) kinase during bovine oocyte maturation. The time sequence for GVBD was not
      different between oocytes cultured with or without wortmannin. Most of the
      cultured oocytes were at the filamentous bivalents stage after 4 h of culture.
      Six hours after the start of culture, most of the oocytes possessed germinal
      vesicles with condensed bivalent, and by 10 h of culture nearly all of the
      cultured oocytes underwent GVBD. A gradual increase in MPF activity until 12 h of
      culture was observed in the presence and absence of wortmannin. A sharp decrease
      in MPF activity in oocytes cultured without wortmannin treatment was recorded at
      14 h of culture. Thereafter, MPF regained activity, reaching a maximum level at
      20 to 24 h of culture. For oocytes cultured with wortmannin, no decline in the
      activity of MPF was observed during the interval from 12 to 24 h of culture. For
      these oocytes the MPF activity remained nearly stable during this transition
      until the end of incubation. The presence of wortmannin in the maturation medium
      did not alter MAP kinase activity. Taken together, these observations indicate
      that inhibition of PI 3-kinase does not modulate the time sequence of GVBD or the
      pattern of MAP kinase activity in bovine oocytes. However, PI 3-kinase might be
      one of the molecules that regulate the sharp reduction in the activity of MPF
      during the MI/MII transition.

PMID- 10968423
TI  - Short time priming of pig cumulus-oocyte complexes with FSH and forskolin in the
      presence of hypoxanthine stimulates cumulus cells to secrete a meiosis-activating
      substance.
AB  - This study evaluated the effect of forskolin and FSH on pig oocyte maturation
      when cultured in a maturation inhibiting system. Ovaries from prepubertal gilts
      were collected at a local slaughterhouse. Oocytes were cultured in a hypoxanthine
      (HX 4 mM) containing M 199 for 24 or 40 h with or without forskolin and FSH
      treatment. After the culture, we examined germinal vesicle breakdown (GVBD) and
      polar body (PB) formation. Two experiments were designed. (1) Cumulus enclosed
      oocytes (CEO) were cultured for 24 or 40 h with or without different doses of
      forskolin and FSH. (2) CEO were primed by forskolin and FSH for different times
      and then transferred into an HX-medium for a further culture. The total culture
      period was 24 h. The results revealed that 4 mM HX markedly prevented pig CEO
      from undergoing GVBD. After 24 and 40 h culture, FSH (50-200 U/L) stimulated
      oocytes to resume meiosis by overcoming the inhibition of HX. Both GVBD and PB
      formation were increased (P < 0.002 and 0.01 respectively) after 40 h exposed to
      FSH. Forskolin showed a biphasic effect on CEO maturation. Within 24 h forskolin,
      in combination with HX, inhibited oocytes maturation. The GVBD percentage was
      significantly decreased compared to HX alone group (2% to 20%, P < 0.01), whereas
      no inhibition was observed after 40 h of culture. The second experiment showed
      that forskolin (3 microM) and FSH (100 U/L) priming CEO could time-dependently
      induce oocyte maturation by overriding the inhibition of HX. After 30 and 60 min
      priming by FSH or forskolin, the GVBD and PB percentage was significantly
      increased (P < 0.002 and 0.01 respectively). No difference of GVBD percentage was
      observed between FSH short time priming group and FSH long time presentation
      group. In conclusion, we found that forskolin and FSH in vitro can stimulate pig
      cumulus cells to secrete a meiosis-activating substance which induces the oocyte
      to overcome the inhibition of hypoxanthine and undergo GVBD.

PMID- 10968424
TI  - Comparison of open pulled straw (OPS) vs glass micropipette (GMP) vitrification
      in mouse blastocysts.
AB  - The purpose of this study was to investigate the use of a glass micropipette
      (GMP) as a vessel for vitrification of mouse blastocysts, and to compare the post
      thaw survival of these blastocysts with those cooled in open pulled straws (OPS).
      The GMP vessel permits higher freezing and warming rates than OPS due to the
      higher heat conductivity of glass and lower mass of the solution containing the
      embryos. Groups of 6 mouse blastocysts were sequentially placed into 2
      vitrification solutions before being loaded into either the OPS or GMP vessels
      and immersed into LN2 within 20 to 25 sec. Post-thaw blastocysts were serially
      washed in 0.25 and 0.15 M sucrose in holding medium (HM) and modified human tubal
      fluid medium (mHTF), each for 5 min, and then cultured in mHTF supplemented with
      10% FCS for 24 h. The rate of blastocyst re-expansion did not differ
      significantly for OPS (93.5%) and GMP (95.0%) methods (P<0.05). The hatching rate
      in OPS (88.7%) was similar to that in GMP (90.0%) but was lower than for the
      unvitrified control embryos (98.3%, P<0.05). To determine the optimal embryo
      population per GMP vessel, the pipettes were loaded with 2 to 10 embryos. The
      rate of blastocyst re-expansion after vitrification was significant for 2 to 4
      embryos than for 6 to 10 embryos per vessel. In addition, the rate of blastocyst
      re-expansion was significantly lower if blastocysts were vitrified in the wide
      rather than the narrow portion of the micropipette (100 vs 87.5%; P<0.05) even
      when only 4 blastocysts were loaded per vessel. These results indicate that both
      vitrification vessels can provide high rates of embryo survival. However, the GMP
      vessel does not need a cap to protect the vessel from floating after immersion in
      LN2. The number and location of the embryos (narrow versus wide portion of
      capillary) were considered to be limiting factors to the viability of mouse
      embryos.

PMID- 10968425
TI  - Effect of intrauterine treatment with prostaglandin E2 prior to insemination of
      mares in the uterine horn or body.
AB  - Two trials were conducted to investigate the effects of intrauterine infusion of
      PGE2 and uterine horn insemination on pregnancy rates in mares achieved by
      breeding with a suboptimal number of normal spermatozoa. Estrus was synchronized
      and mares were teased daily with a stallion to detect estrus. Mares in estrus
      were examined by transrectal palpation and ultrasonography to monitor follicular
      status. On the first day a 35-mm diameter follicle was present, hCG (1500 IU, iv)
      was administered and the mares were bred the next day. Mares (Trial 1, n = 34;
      Trial 2, n = 28) were inseminated with 25 million total spermatozoa from either a
      stallion with good semen quality (Trial 1) or poor semen quality (Trial 2). In
      each trial, mares were assigned to 1 of 4 treatment groups as follows: Group PGE
      HI - infusion of 0.25 mg PGE2 into the proximal end of the uterine horn
      ipsilateral to the dominant follicle 2 h prior to insemination in the proximal
      end of the same uterine horn; Group PGE-BI - infusion of 0.25 mg PGE2 into the
      proximal end of the uterine horn ipsilateral to the dominant follicle 2 h prior
      to insemination in the uterine body; Group SAL-HI - infusion of 1 mL sterile
      saline into the proximal end of the uterine horn ipsilateral to the dominant
      follicle 2 h prior to insemination in the proximal end of the same uterine horn;
      or Group SAL-BI - infusion of 1 mL sterile saline into the proximal end of the
      uterine horn ipsilateral to the dominant follicle 2 h prior to insemination in
      the uterine body. After breeding, mares were examined daily by transrectal
      ultrasonography to confirm ovulation, and were re-examined 14 to 16 d after
      ovulation for pregnancy status. Data were analyzed by Chi-square. Overall
      pregnancy rates were 59% for stallion 1 and 29% for stallion 2. Group pregnancy
      rates did not differ for mares bred by either stallion (P > 0.10). Pregnancy
      rates were not altered by horn insemination for either stallion (P > 0.10).
      Intrauterine infusion of PGE2 improved pregnancy rate in mares bred by the
      stallion with good quality semen (P < 0.05), but did not alter pregnancy rate in
      mares bred by the stallion with poor quality semen (P > 0.10). Further research
      is warranted to determine if intrauterine infusion of PGE2 will enhance
      spermatozoal colonization of the oviduct and pregnancy rates in mares, and if PGE
      treatment will improve pregnancy rates achieved by subfertile stallions.

PMID- 10968426
TI  - Experimenting with direct-to-consumer advertising.

PMID- 10968427
TI  - Vasopeptidase inhibition and angio-oedema.

PMID- 10968428
TI  - Ganciclovir resistance: a matter of time and titre.

PMID- 10968429
TI  - Long-term safety and efficacy of omeprazole in gastro-oesophageal reflux disease.

PMID- 10968430
TI  - White matters: small vessels and slow thinking in old age.

PMID- 10968431
TI  - Elusiveness of ideal approach to Pseudomonas aeruginosa infection complicating
      cystic fibrosis.

PMID- 10968432
TI  - Thyroid (neuro)myopathy.

PMID- 10968433
TI  - Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise
      tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.
AB  - BACKGROUND: We aimed to assess in patients with congestive heart failure whether
      dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE)
      with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone
      with lisinopril on functional capacity and clinical outcome. METHODS: We did a
      prospective, randomised, double-blind, parallel trial of 573 patients with New
      York Heart Association (NYHA) class II-IV congestive heart failure, left
      ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor.
      Patients were randomly assigned omapatrilat at a daily target dose of 40 mg
      (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The
      primary endpoint was improvement in maximum exercise treadmill test (ETT) at week
      12. Secondary endpoints included death and comorbid events indicative of
      worsening heart failure. FINDINGS: Week 12 ETT increased similarly in the
      omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly
      well tolerated, but there were fewer cardiovascular-system serious adverse events
      in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%],
      p=0.04). There was a suggestive trend in favour of omapatrilat on the combined
      endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio
      0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the
      composite of death, admission, or discontinuation of study treatment for
      worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA
      class more than lisinopril in patients who had NYHA class III and IV (p=0.035),
      but not if patients with NYHA class II were included. INTERPRETATION: Our
      findings suggest that omapatrilat could have some advantages over lisinopril in
      the treatment of patients with congestive heart failure. Thus use of
      vasopeptidase inhibitors could constitute a potentially important treatment for
      further improving the prognosis and well being of patients with this disorder.

PMID- 10968434
TI  - Normalised intrinsic mortality risk in liver transplantation: European Liver
      Transplant Registry study.
AB  - BACKGROUND: No model exists for liver transplantation to estimate the mortality
      risk in a given patient, and no standard by which to assess performance in
      different centres. We investigated the intrinsic mortality risk in the absence of
      known mortality risk factors. METHODS: We identified mortality risk factors and
      risk ratios quantified in data from the European Liver Transplant Registry
      (22,089 patients at 102 centres in 18 countries) registered from 1988 to 1997. To
      develop a model of the intrinsic risk and the risk ratios for specific factors,
      univariate and multivariate analyses were done separately for the overall
      population, for adults, and for children younger than 15 years, and the number of
      deaths were estimated. We validated the model by comparing mortality in patients
      without risk factors with the model-adjusted mortality in patients with risk
      factors. FINDINGS: Overall 5-year and 8-year actuarial survival was 66% (95% CI
      65-66) and 61% (60-62). 65% of deaths occurred within 6 months.
      Retransplantation, transplantation for cancer, acute liver failure, fewer than 20
      split-liver grafts per year, and a centre workload of fewer than 25 transplants
      per year were the main risk factors of 12 identified factors. 1-year and 5-year
      death rates among adults with no risk factors were similar to model estimates (15
      [13-16] vs 14% [13-15], and 22 (20-24) vs 23% [21-24]). Corresponding data for
      paediatric transplants were 9% (7-12) compared with 11% (9-12) and 13% (10-17)
      compared with 14% (11-16). The reduction of mortality risk in high-volume centres
      was even greater in patients without risk factors (48 vs 23%, p<0.001).
      INTERPRETATION: The normalised intrinsic mortality risk can be combined with the
      relative risk ratios of known risk factors to better estimate the mortality risk
      of a given procedure in a given patient. Centres can assess performance by
      removing potential bias of donor and recipient selection.

PMID- 10968435
TI  - Relation between age-related decline in intelligence and cerebral white-matter
      hyperintensities in healthy octogenarians: a longitudinal study.
AB  - BACKGROUND: White-matter hyperintensities are commonly found on magnetic
      resonance imaging (MRI) of elderly people with or without dementia. Studies of
      the relation between severity of white-matter hyperintensities and cognitive
      impairment have had conflicting results. We undertook a longitudinal study of age
      related decline in intellectual function and MRI at age 80 years. METHODS: From a
      cohort of 698 people born in 1914 and living in seven municipalities in Denmark,
      68 healthy non-demented individuals had been tested with the Wechsler adult
      intelligence scale (WAIS) at ages 50, 60, and 70, and they agreed to further WAIS
      testing at age 80, and cerebral MRI at age 80-82 (mean age 82.3 years). We scored
      separately the numbers of periventricular and deep white-matter hyperintensities.
      FINDINGS: Scores for periventricular hyperintensities in this sample included all
      possible degrees of severity, but no participant scored more than 75% of maximum
      for deep white-matter hyperintensities. Neither type was related to the WAIS IQs
      of the 80-year assessment, but both were significantly associated with decline in
      performance IQ from age 50 to age 80 years (bivariate correlation coefficients
      0.32, p=0.0087, and 0.28, p=0.0227, respectively). An analysis based on two WAIS
      subtests showed that the association between white-matter hyperintensities and
      cognitive impairment was significant only for cognitive decline in the decade 70
      80 years. INTERPRETATION: Both periventricular and deep white-matter
      hyperintensities are related to decline in intelligence but, in healthy
      octogenarians, the cumulative effect of these features alone explains only a
      small part of the large differences among individuals in age-related decline in
      intelligence. Interpretation of the presence and severity of white-matter
      hyperintensities in a diagnostic context must be done cautiously.

PMID- 10968436
TI  - The uncertainty principle and industry-sponsored research.
AB  - BACKGROUND: Reporting of pharmaceutical-industry-sponsored randomised clinical
      trials often result in biased findings, either due to selective reporting of
      studies with non-equivalent arms or publication of low-quality papers, wherein
      unfavourable results are incompletely described. A randomised trial should be
      conducted only if there is substantial uncertainty about the relative value of
      one treatment versus another. Studies in which intervention and control are
      thought to be non-equivalent violates the uncertainty principle. METHODS: We
      examined the quality of 136 published randomised trials that focused on one
      disease category (multiple myeloma) and adherence to the uncertainty principle.
      To evaluate whether the uncertainty principle was upheld, we compared the number
      of studies favouring experimental treatments over standard ones. We analysed data
      according to the source of funding. FINDINGS: Trials funded solely or in part by
      35 profit-making organisations had a trend toward higher quality scores (mean
      2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or
      other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty
      principle was upheld, with 44% of randomised trials favouring standard treatments
      and 56% innovative treatments (p=0.17); mean and median preference evaluation
      scores were 3.7 (1.0) and 4. However, when the analysis was done according to the
      source of funding, studies funded by non-profit organisations maintained
      equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a
      greater extent than randomised trials supported solely or in part by profit
      making organisations (74% vs 26%; p=0.004). INTERPRETATION: The reported bias in
      research sponsored by the pharmaceutical industry may be a consequence of
      violations of the uncertainty principle. Sponsors of clinical trials should be
      encouraged to report all results and to choose appropriate comparative controls.

PMID- 10968437
TI  - Rate of heart failure and 1-year survival for older people receiving low-dose
      beta-blocker therapy after myocardial infarction.
AB  - BACKGROUND: Many older people do not receive beta-blocker therapy after
      myocardial infarction or receive doses lower than those tested in trials, perhaps
      because physicians fear that beta-blockers may precipitate heart failure. We
      examined the relation between use of beta-blockers, the dose used, and hospital
      admission for heart failure and 1-year survival in a cohort of all older patients
      surviving myocardial infarction in Ontario, Canada. METHODS: We collected data on
      a cohort of 13,623 patients aged 66 years or older who were discharged from
      hospital after a myocardial infarction and who did not receive beta-blocker
      therapy or received low, standard, or high doses. We used Cox's proportional
      hazards models to study the association of dose with admission for heart failure
      and survival with adjustment for factors including age, sex, and comorbidity.
      FINDINGS: Among 8232 patients with no previous history of heart failure,
      dispensing of beta-blocker therapy was associated with a 43% reduction in
      subsequent admission for heart failure (adjusted risk ratio 0.57 [95% CI 0.48
      0.69]) compared with patients not dispensed this therapy. Among the 4681 patients
      prescribed beta-blockers, the risk of admission was greater in the high-dose than
      in the low-dose group (1.53 [1.01-2.31]). Among all 13,623 patients in the
      cohort, 2326 (17.1%) died by 1 year. Compared with those not dispensed beta
      blocker therapy, the adjusted risk ratio for mortality was lower for all three
      doses (low 0.40 [0.34-0.47], standard 0.36 [0.31-0.42], high 0.43 [0.33-0.56]).
      INTERPRETATION: Compared with high-dose beta-blocker therapy, low-dose treatment
      is associated with a lower rate of hospital admission for heart failure and has a
      similar 1-year survival benefit. Our findings support the need for a randomised
      controlled trial comparing doses of beta-blocker therapy in elderly patients.

PMID- 10968439
TI  - Crusted scabies looking like psoriasis.

PMID- 10968438
TI  - Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of
      solid-organ transplants.
AB  - BACKGROUND: Concerns have been raised about emergence of ganciclovir resistance
      as a result of the advent of both routine oral ganciclovir prophylaxis and highly
      potent immunosuppression. We retrospectively assessed the occurrence of
      ganciclovir-resistant cytomegalovirus disease among transplant recipients who had
      received oral ganciclovir prophylaxis and highly potent immunosuppression.
      METHODS: We studied 240 recipients of liver, kidney, or pancreas transplants.
      Antiviral susceptibility testing of blood cytomegaloviral isolates was done when
      patients failed to respond to intravenous ganciclovir treatment for symptomatic
      cytomegalovirus infection. Portions of the UL97 gene associated with ganciclovir
      resistance were sequenced in cytomegalovirus isolates with phenotypic resistance
      to ganciclovir. FINDINGS: Ganciclovir-resistant cytomegalovirus disease developed
      in five (7%) of 67 seronegative recipients of cytomegalovirus-seropositive organs
      (D+/R-) compared with none of 173 seropositive recipients (p=0.002). Among the 25
      (10.4%) patients who developed cytomegalovirus disease within 1 year after
      transplantation, five had ganciclovir-resistant cytomegalovirus disease. Among
      D+/R-transplant recipients, ganciclovir-resistant cytomegalovirus disease was
      more common among the group receiving the most potent immunosuppression--ie,
      recipients of kidney and pancreas or pancreas alone (four of 19) compared with
      all other transplant recipients (one of 48, p=0.02). Ganciclovir-resistant
      cytomegalovirus disease was diagnosed at a median of 10 months after
      transplantation (range 7-12) after lengthened exposure to ganciclovir, was
      associated with previously described mutations of the UL97 gene, and led to
      serious clinical complications. INTERPRETATION: Ganciclovir-resistant
      cytomegalovirus is an important cause of late morbidity among D+/R- transplant
      recipients who have had lengthened exposure to ganciclovir and have received
      highly potent immunosuppression. Strategies to reduce this complication,
      especially among D+/R- patients, are warranted.

PMID- 10968440
TI  - Predictive value of T-wave alternans for arrhythmic events in patients with
      congestive heart failure.
AB  - Measurement of microvolt level T-wave alternans in the surface electrocardiogram
      is a novel way to assess the risk of ventricular arrhythmias. Seven tests of
      arrhythmic risk, including T-wave alternans, were undertaken in 107 consecutive
      patients with congestive heart failure and no history of sustained ventricular
      arrhythmias; the patients were followed up for arrhythmic events during the next
      18 months. Of the patients with events, 11 had positive and two indeterminate T
      wave alternans results; there were no arrhythmic events among patients with
      negative T-wave alternans results. Of the seven tests, only T-wave alternans was
      a significant (p=0.0036) and independent predictor of arrhythmic events.

PMID- 10968441
TI  - Gilbert's syndrome and hyperbilirubinaemia in ABO-incompatible neonates.
AB  - We asked whether UDP glucuronosyltransferase (UGT) gene promoter polymorphism
      (Gilbert's syndrome) would increase hyperbilirubinaemia in direct Coombs'
      negative ABO-incompatible neonates, as seen in other combinations with this
      condition. 40 ABO-incompatible and 344 ABO-compatible controls had an allele
      frequency of 0.35 for the variant promoter gene. The incidence of
      hyperbilirubinaemia was significantly higher only in the former who were also
      homozygotes for the variant UGT promoter, compared with ABO-incompatible babies
      homozygous for the normal UGT promoter (43% vs 0, p=0.02), and with ABO
      compatible controls of all UGT genotypes combined (relative risk 5.65, 95% CI
      2.23-14.31). Gilbert's syndrome is a determining factor for neonatal
      hyperbilirubinaemia ABO incompatibility.

PMID- 10968442
TI  - Retroperitoneal endoscopic debridement for infected peripancreatic necrosis.
AB  - Standard management of infected peripancreatic necrosis consists of open surgical
      debridement and lavage--a traumatic intervention with substantial morbidity and
      mortality. As an alternative and novel approach with minimum invasiveness, we
      present fenestration of the gastric wall and debridement of infected necrosis by
      direct retroperitoneal endoscopy. In three patients, this strategy led to rapid
      clinical improvement and no serious complications. Transgastric endoscopic
      therapy may be a less traumatic alternative to surgery and should be further
      assessed in prospective studies.

PMID- 10968443
TI  - Association between infant growth before onset of juvenile type-1 diabetes and
      autoantibodies to IA-2. Netherlands Kolibrie study group of childhood diabetes.
AB  - Secular growth changes have not been linked with type-1 diabetes. Longitudinal
      growth analysis in prediabetic type-1 children indicated increased body mass
      index (BMI) in the first year of life and an increased growth in length in the
      next 2 years. These heavier and taller children presented with autoantibodies
      against pancreatic islet tyrosine phosphatases at diagnosis many years later. It
      is possible that increased BMI during the first year of life and the development
      of such autoantibodies represents an additional risk marker towards earlier
      clinical onset of disease.

PMID- 10968444
TI  - Hyponatraemia associated with lamotrigine in cranial diabetes insipidus.
AB  - We report the cases of two children with cranial diabetes insipidus who were
      treated with lamotrigine for seizures and who had accompanying changes in
      desmopressin requirements. Lamotrigine is a new anticonvulsant chemically
      unrelated to other existing antiepileptic drugs. Studies suggest it acts at
      voltage-sensitive sodium channels and also decreases calcium conductance. Both of
      these mechanisms of action are shared by carbamazepine, which can cause
      hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is
      possible that the effect of lamotrigine on fluid balance in the cases described
      is also centrally mediated.

PMID- 10968445
TI  - New Dartmouth Atlas: improving US cardiac care?

PMID- 10968446
TI  - Putting the capacity into capacity building in South Sudan.

PMID- 10968447
TI  - India challenges UN agencies' estimates of HIV prevalence.

PMID- 10968448
TI  - Concerns raised about Botswana's proposed HIV-disclosure law.

PMID- 10968449
TI  - Pakistan's treatment of women criticised.

PMID- 10968450
TI  - No-fault awards for babies with cerebral palsy in Ireland?

PMID- 10968451
TI  - Public health in Europe.
AB  - Any attempt to describe public health in Europe faces the twin problems of
      defining Europe and of dealing with the diversity of health and health systems it
      contains. Health status varies considerably between countries. In some, health is
      improving, with substantial decreases in heart disease in many western and
      central European countries. In others, especially in the former Soviet Union,
      there is concern about the rapid increase in tuberculosis and AIDS. A national
      analysis does, however, conceal a substantial variation within countries, between
      regions, and between social classes. The responses to these threats to health are
      also diverse. A few countries have developed effective mechanisms to design and
      implement appropriate policies but, in many countries, the public-health
      community is weak. In particular, public health has largely failed in its role as
      an advocate of the health of the population. There are, however, many encouraging
      signs that this may change in the future.

PMID- 10968452
TI  - European cardiology: 50 years.

PMID- 10968453
TI  - Prader-Willi syndrome.

PMID- 10968454
TI  - Treatment of Gaucher's disease with OGT 918.

PMID- 10968455
TI  - Treatment of Gaucher's disease with OGT 918.

PMID- 10968456
TI  - Prevention of hypertension and stroke in Africa.

PMID- 10968457
TI  - Prevention of hypertension and stroke in Africa.

PMID- 10968458
TI  - Parity and breast cancer in BRCA1/BRCA2 carriers.

PMID- 10968459
TI  - Thyroid FNA and benign thyroid disease.

PMID- 10968460
TI  - Global health policy.

PMID- 10968461
TI  - Global health policy.

PMID- 10968462
TI  - Global health policy.

PMID- 10968463
TI  - Space flight related anorexia.

PMID- 10968464
TI  - Sentinel-node biopsy sampling in breast cancer.

PMID- 10968465
TI  - Systolic blood pressure and mortality.

PMID- 10968466
TI  - Systolic blood pressure and mortality.

PMID- 10968467
TI  - Systolic blood pressure and mortality.

PMID- 10968468
TI  - Evidence-based illiteracy or illiterate evidence.

PMID- 10968469
TI  - Life after sanctions: the fate of Iraq.

PMID- 10968470
TI  - Life after sanctions: the fate of Iraq.

PMID- 10968472
TI  - Tailored treatment for heart failure.

PMID- 10968471
TI  - Attraction of mosquitoes to pregnant women.

PMID- 10968473
TI  - A surgical amputation in 2nd century Rome.

PMID- 10968474
TI  - Nongenomic actions of steroids--from the laboratory to clinical implications.
AB  - In the classical concept of steroid action, steroids bind to cytoplasmic
      receptors and modulate nuclear transcription after translocation of steroid
      receptor complexes into the nucleus. Due to similarities of molecular structure,
      receptors for steroids, retinoids, vitamin D3 and thyroid hormone are considered
      to represent a superfamily of receptors. While genomic steroid effects been
      evident for several decades, rapid effects of steroids have been characterized
      only recently. These rapid actions are likely to be transmitted by specific
      membrane receptors. Binding sites in membranes have been characterized which
      display binding features compatible with an involvement in rapid steroid
      signaling. Characteristics of putative membrane receptors are completely distinct
      from those of intracellular steroid receptors, a fact which is further supported
      by the inability of classic steroid receptor antagonists to suppress nongenomic
      steroid actions. The cloning and functional expression of a putative progesterone
      membrane receptor has been achieved. Drugs that specifically modulate nongenomic
      action alone or even both genomic and nongenomic actions may be applied in
      various areas such as the cardiovascular and central nervous systems, and
      treatment of infertility and electrolyte homeostasis.

PMID- 10968475
TI  - Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective
      multicenter study.
AB  - This retrospective multicenter study was designed to survey the management of
      childhood and adolescent hyperthyroidism in six pediatric endocrinological units
      in Germany. Fifty-six patients aged between 1.1 and 17.0 yr (median 10.5 yr) were
      enrolled. Data were collected retrospectively from the patients' records by a
      trained pediatric endocrinologist using standardized questionnaires. After the
      diagnosis of hyperthyroidism was established on the basis of clinical and
      biological findings, treatment with antithyroid drugs (carbimazole, methimazole,
      thiamazole, propylthiouracil) was started in all patients. In 55/56 of the
      patients treated with antithyroid drugs, euthyroidism was achieved (98%).
      However, 26 patients (47%) were still hyperthyroid after discontinuation of the
      medication. Eight children with continued hyperthyroidism ultimately underwent
      subtotal thyroidectomy 13-136 (median 28) months after the initial diagnosis.
      Management principles of the participating centers were heterogeneous. As a
      consequence, prospective multicenter studies are urgently needed to establish
      clear standards for the diagnosis and therapy of childhood hyperthyroidism.

PMID- 10968476
TI  - Relationship between serum growth hormone binding protein levels and height in
      young men.
AB  - The biochemical mediators responsible for variations in stature among normal
      subjects are largely unknown. To obtain some initial information about potential
      endocrine factors, we measured the serum concentrations of GH, IGF-1, IGFBP-3 and
      GHBP in healthy young men shorter than 159 cm and taller than 187 cm. We studied
      14 volleyball and basketball players (tall group), and 14 jockey students from a
      horse racetrack (short group). A careful medical history was taken, including
      dietary intake, and physical examination with special attention to the possible
      presence of genetic stigmata was performed. Serum prealbumin was determined as an
      index of nutritional status. A buccal smear was performed to exclude
      Klinefelter's syndrome. The BMI and serum prealbumin levels were comparable in
      both groups of individuals. The nutritional survey, however, revealed that the
      tall subjects had a higher intake of calories (42.2+/-11.2 vs. 30.1+/-15.15
      kcal/kg, p<0.05), and protein (1.5+/-0.6 vs. 0.8+/-0.4 mg/kg, p<0.01). Serum
      concentrations of GHBP did not differ in the two groups (0.95+/-0.37 nmol/l in
      the tall, and 0.95+/-0.53 nmol/l in the short group), and did not correlate with
      height, serum IGF-I levels, or BMI. We observed a significant difference in the
      serum concentrations of IGF-I in the two groups of individuals (42.02+/-9.37
      nmol/l in the tall and 31.79+/-3.18 nmol/l in the short group, p<0.05), and this
      growth factor showed a positive correlation with height (r = 0.5, p<0.01). These
      preliminary findings suggest that final height differences in young men do not
      appear to be mediated by variations in GHBP concentrations.

PMID- 10968477
TI  - Prediction of height velocity of prepubertal children with growth hormone
      deficiency in the first year of treatment with recombinant human growth hormone.
AB  - AIM: Several methods have been developed to predict the outcome of growth hormone
      (GH) therapy in children with growth hormone deficiency (GHD). METHODS: Over 50
      factors for each of 92 prepubertal patients with GHD (26 patients with total and
      45 patients with partial GHD, 21 patients with neurosecretory dysfunction) were
      collected and included in multiple regression analyses and other nonlinear models
      to predict height velocity (HV) (cm/yr) in the first year of treatment.
      Afterwards the model was validated by two other cohorts of patients from other
      universities, which followed the same treatment regime as our clinic. RESULTS:
      Twelve parameters had a significant correlation to HV (p<0.05) and a coefficient
      of determination >20%. Two parameters (In BA, In GHmax) showed a coefficient of
      determination >60% for children with GHD in multiple regression analysis. The
      validation of the mathematical model against another data set showed different
      results. GH was measured by the same method, but BA was scored at the first
      clinic as in our clinic by only one doctor and in the other university by several
      radiologists. The accuracy of prediction in the first clinic was significantly
      higher than in the other university. CONCLUSION: This model demonstrates that
      exact scoring of BA and precise measurement of GHmax in the stimulation test is
      necessary, and if carried out carefully leads to useful prediction values for
      determining height velocity.

PMID- 10968478
TI  - Efficacy of recombinant human growth hormone in children with juvenile rheumatoid
      arthritis and growth failure.
AB  - Ten patients with juvenile rheumatoid arthritis (JRA) and growth failure were
      treated with recombinant human growth hormone (GH) for 1 to 3 years at a dosage
      of 0.57 IU/kg/wk. All the patients had been on prednisone at a mean dosage of
      4.12 mg p.o. daily. GH was low in one patient, two patients had a borderline
      level and seven patients had adequate response to provocative tests or post-sleep
      measurement. Serum IGF-I was found to be low in five of six patients. Mean growth
      velocity increased from 2.45 cm/yr to 4.79 cm/yr after 1 year's treatment with GH
      (P<0.004). Six patients continued on GH treatment for a second year and continued
      to have a better growth velocity, with a mean of 5.43 cm/yr (P<0.014). Two
      patients entered puberty during the second year of GH treatment. This study
      demonstrates the potential beneficial effect of GH treatment in patients with JRA
      with growth failure of systemic onset or polyarticular onset who are on
      prednisone. Further study is needed to determine the long-term effect of GH
      treatment on ultimate height.

PMID- 10968479
TI  - Differences of hexarelin-induced prolactin and cortisol responses between
      prepubertal and early pubertal short children and lack of correlation with
      gonadotropin-releasing hormone-induced gonadotropin response.
AB  - Hexarelin (HEX), a synthetic hexapeptide with strong GH-stimulating activity, is
      known to induce the release of prolactin (PRL) and cortisol (F). The responses of
      GH and F vary according to age and pubertal development, correlating with serum
      levels of sex steroids, while the release of PRL does not. We evaluated GH, PRL
      and F responses to HEX (2 microg/kg i.v.) in 19 children with short stature, 12
      prepubertal (Tanner stage I) and 7 early pubertal (stage II), and their
      correlation with those of FSH and LH to GnRH and with the serum levels of
      testosterone (T) or estradiol (E2). At baseline, the GH, PRL, F and sex steroid
      serum levels did not vary in the two groups of patients. HEX induced a strong GH
      and a slight PRL increase in prepubertal and early pubertal children, with no
      differences in the extent of the response, while F secretion was not affected in
      either group; these responses did not correlate with those of the gonadotropins
      to GnRH nor with basal T or E2.

PMID- 10968480
TI  - No relationship between leptin and cortisol in obese children and adolescents.
AB  - Recent findings have shown that leptin downregulates the steroid producing system
      in the adrenal. We studied the interactions of leptin, insulin and cortisol in
      obese children and adolescents at different stages of maturation. In 44 boys (age
      11+/-3.1 yr, body mass index [BMI] 29+/-5.3 [mean +/- SD]) and 35 girls (age
      11.4+/-2.6 yr, BMI 29+/-4.3), blood levels of leptin, insulin, cortisol, and
      glucose were determined. Fat mass (FM) was calculated by bioelectrical impedance.
      No significant differences were found between boys and girls with respect to
      humoral and anthropometric characteristics. When children were divided according
      to maturation stage (prepubertal, pubertal, and late/postpubertal) insulin was
      higher in the more mature groups (p<0.01) and leptin was higher in the pubertal
      group (p=0.03). In the prepubertal and pubertal groups, the expected positive
      relationship between adiposity and leptin was found although the magnitude of
      this association decreased with maturity. In none of the groups studied was
      cortisol significantly correlated to leptin. Insulin (p=0.03) and glucose
      (p=0.01) were positively associated with cortisol in the prepubertal group after
      adjustment for adiposity. However, in the pubertal group an inverse correlation
      was found between insulin and cortisol (p=0.03), and between insulin and glucose
      after control for adiposity. In the late/ postpubertal group, no significant
      correlations were found between estimates of adiposity and humoral parameters
      even after adjustment for gender. Stepwise multiple regression failed to detect a
      significant influence of cortisol to explain the variation in leptin, and vice
      versa. BMI contributed to the variation in leptin (adj. R2 =0.275, p<0.0001), and
      glucose added 5% to the variation in cortisol (p=0.03). The results do not
      confirm the inverse association between leptin and cortisol found in adults.
      Although BMI reflects levels of leptin, it is likely that several other factors
      in conjunction with fatness modulate the relationship with leptin. Whether leptin
      per se exerts an influence on the hypothalamic-adrenal-adipo axis remains to be
      investigated in longitudinal studies.

PMID- 10968481
TI  - Insulin and insulin resistance index are not independent determinants for the
      variation in leptin in obese children and adolescents.
AB  - Recent findings have questioned the independent influence of insulin on leptin.
      We studied whether insulin contributes to leptin in obese children, independent
      of confounding parameters, such as total adiposity, fasting insulin resistance
      index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of
      leptin, insulin, glucose, and triglycerides were determined. The fasting insulin
      resistance index (FIRI) was calculated, and body composition was assessed by
      means of impedance. Leptin and glucose were higher in girls, and all estimates of
      adiposity were significantly associated with leptin. However, when adjusted for
      adiposity, the relationship between insulin and leptin, and also between FIRI and
      leptin, remained significant in boys and girls (p<0.05). Although several
      regression models were tested, neither insulin nor FIRI were found to contribute
      significantly and independently to leptin. BMI together with triglycerides and
      FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46,
      p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin
      (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood
      and adolescent obesity, total adiposity but not insulin or insulin resistance
      index is the main determinant for leptin. In contrast to obese girls, the fat
      free mass and triglycerides contribute significantly to the variation in leptin
      in obese boys. The biological significance for these findings should be
      elucidated in longitudinal studies.

PMID- 10968483
TI  - Growth in four patients on combined treatment with LHRH analogue and growth
      hormone after renal transplantation.
AB  - Four short pubertal boys were treated with LHRHa (leuprolide) and GH after renal
      transplantation, and followed until adult height. This combined therapy was not
      successful in increasing growth. Although this study must be considered
      preliminary because of the small number of patients and the lack of a matched
      control group, it shows for the first time that this combined therapy (GH +
      LHRHa) administered to short, pubertal boys after renal transplantation was not
      successful in increasing growth. Further studies are required to reach definitive
      conclusions.

PMID- 10968482
TI  - Evaluation of bone mineral metabolism in children receiving carbamazepine and
      valproic acid.
AB  - Dual energy X-ray absorptiometry (DXA) was used to assess lumbar spine (L2-4) and
      femoral neck bone mineral density (BMD) in 36 children taking either
      carbamazepine or valproic acid for longer than one year, for generalized
      idiopathic epilepsy. Patients were matched with controls. Biochemical parameters
      of bone mineral metabolism were also measured. BMD values at both the femur neck
      and lumbar spine in both the carbamazepine and valproic acid groups were not
      significantly different from that of the control group. Serum levels of calcium
      were subnormal and alkaline phosphatase levels were high in the carbamazepine
      group. Urinary calcium levels were significantly lower in both groups than in the
      control group (p< or =0.05) and also significantly lower in the valproic acid
      group than in the carbamazepine group (p< or = 0.05). There were no other
      significant biochemical changes in either group. In conclusion, the results
      suggest that valproic acid and carbamazepine monotherapies have minimal effects
      on bone mineral metabolism, but routine monitoring of risk and consideration of
      prophylactic vitamin D supplementation is important.

PMID- 10968484
TI  - Combined 21-hydroxylase and 11beta-hydroxylase deficiency: patient report and
      molecular basis.
AB  - A female newborn (46, XX) with ambiguous genitalia was initially diagnosed by
      biochemical criteria as having classical congenital adrenal hyperplasia caused by
      11beta-hydroxylase deficiency. Shortly after effective treatment was
      administered, she developed a salt-wasting crisis with severe electrolyte
      imbalance. DNA analysis revealed a homozygous splice mutation in the second
      intron of the CYP21 gene, for which both parents were heterozygous. No mutations
      were found in the entire CYP11B1 gene, thus proving that the 11beta-hydroxylase
      deficiency was not caused by a gene mutation but rather was a secondary event,
      possibly due to androgen suppression of 11beta-hydroxylase activity.

PMID- 10968485
TI  - Hajdu-Cheney syndrome with growth hormone deficiency and neuropathy.
AB  - A Hajdu-Cheney syndrome is a very rare congenital dysplastic bone disease
      including acro-osteolysis, short stature, characteristic facies, osteopenia,
      abnormalities of spine, skull and long bones. A 9 year-old boy presented at our
      clinic with a chief complaint of short stature and frequent lower respiratory
      tract infections. He had typical physical and radiographic features of Hajdu
      Cheney syndrome associated with growth hormone (GH) deficiency and peripheral
      motor neuropathy. To our knowledge, this is the first report describing GH
      deficiency and neuropathy in Hajdu-Cheney syndrome.

PMID- 10968486
TI  - Familial brachyolmia.
AB  - Brachyolmia is characterized clinically by short stature and radiographically by
      generalized platyspondyly without significant long bone abnormalities. A healthy
      13-(8/12) year-old girl was referred for evaluation of short stature. The parents
      were first cousins. She had two older brothers and a younger brother and sister.
      On examination, her height was 116.2 cm, height SDS -6.2, armspan 135 cm. She had
      completed puberty. Except for her short trunk and lower extremities and mild
      scoliosis, she appeared normal. At 12 years old, the younger brother had short
      stature. His height was 104.7 cm, height SDS -6.2, armspan 116 cm. The younger
      sister was 3 years old. Her height was 84.2 cm, height SDS -2.9, armspan 85 cm.
      Other findings were normal in the younger sister and brother. The other members
      of the family were of normal stature and appearance. The proband's growth hormone
      stimulation tests, thyroid function tests, sex steroids, gonadotropins and blood
      biochemistry were found normal. There were similar radiological findings in the
      three siblings. There was platyspondyly, narrowing of intervertebral spaces in
      all vertebral bodies. The iliac bones were broad. No metaphyseal irregularity and
      normal epiphyses were detected in all patients. No significant changes were seen
      in long bones and skull. According to the physical and radiological findings, the
      patients were evaluated as brachyolmia.

PMID- 10968487
TI  - Androglottia in a young female adolescent with congenital adrenal hyperplasia and
      21-hydroxylase deficiency.
AB  - Vocal disturbances in women with congenital adrenal hyperplasia and androgen
      excess should be extremely rare today since effective substitution with
      glucocorticoids is available. We present a 17 year-old female with congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency and severe virilization
      because of long-term insufficient therapy. Laboratory data showed elevated serum
      levels of testosterone, 17-hydroxyprogesterone, plasma ACTH and a high excretion
      of urinary pregnanetriol. The phoniatric aspect showed a masculine voice. We
      discuss the different effects of androgens on the pubertal larynx and various
      hormonal disturbances that may cause voice changes as well as therapeutic options
      of voice therapy. From the pediatric point of view it might be important to
      perform a phoniatric examination in girls with congenital adrenal hyperplasia
      during puberty in order to monitor androgen effects.

PMID- 10968488
TI  - Re: Leptin in African-American children, by Danadian K, Suprasongsin C, Janosky
      JE, Arslanian S. J Pediatr Endocrinol Metab 1999; 12:639-644.

PMID- 10968489
TI  - The need for antituberculosis drug resistance surveillance in Europe.

PMID- 10968490
TI  - Preflight medical screening of patients.

PMID- 10968491
TI  - Surveillance of antituberculosis drug resistance in Switzerland 1995-1997: the
      central link.
AB  - The purpose of the present paper is to investigate the usefulness of routine
      notification of antituberculosis drug susceptibilities. In Switzerland,
      laboratories have to report susceptibilities to isoniazid, rifampicin,
      ethambutol, and pyrazinamide to the Federal Office of Public Health. All clinical
      and laboratory information on every single tuberculosis case is routinely linked.
      Proportions of drug resistance were calculated and logistic regression was
      applied to evaluate the role of potential risk factors. Eighty percent (1056) of
      all culture-positive tuberculosis cases reported between October 1995 and
      December 1997 were analysed. The strains of 66 (6.3%) patients had resistances to
      at least one drug. Risk factors identified were previous antituberculosis
      treatment (adjusted odds ratio 7.3, 95% confidence interval 3.9-13.6), male sex
      (1.4, 1.1-2.0), and age <65 yrs (1.5, 1.0-2.3). Fourteen cases (1.3%), 13 of them
      foreign-born, were resistant to at least isoniazid and rifampicin. Reporting of
      drug susceptibilities allows routine assessment of the proportion of drug
      resistant tuberculosis and populations at risk. This proportion was found to be
      small in Switzerland. Risk factors were previous treatment for tuberculosis, male
      sex, and age <65 yrs. Resistance to at least isoniazid and rifampicin was
      predominantly found in foreign-born patients.

PMID- 10968492
TI  - Results from 8 yrs of susceptibility testing of clinical Mycobacterium
      tuberculosis isolates in Denmark.
AB  - Increased rates of multidrug-resistant (MDR) tuberculosis (TB) has been reported
      from countries close to Denmark. This study evaluated the incidence of drug
      resistance in Denmark in order to determine the magnitude of the problem.
      Susceptibility testing was performed in isolates from 85.4% of all notified
      patients during 1991-1998. Epidemiological information was retrieved from the
      mandatory notification forms. Total drug resistance remained largely constant,
      although a minor increase was observed in 1997-1998. Monoresistance was observed
      in 7.3%, of the isolates. Among 3.6% polyresistant isolates, resistance to
      isoniazid and streptomycin accounted for 2.8%, whereas MDR accounted for 0.5%.
      The MDR strains displayed different restriction fragment length polymorphism
      (RFLP) patterns, and no matches were identified in the international MDR
      database. Drug resistance in untreated Danes and foreigners were 5.9% and 14.6%,
      respectively. Among Danes and foreigners with previous TB, 6.2% and 22.7% had
      drug resistance, respectively. Increased drug-resistance was found among
      untreated Danes aged 25-54 yrs mainly due to a single isoniazid and streptomycin
      resistant RFLP-cluster. Among all patients with isoniazid and streptomycin
      resistance, 77.0% had clustered strains. In conclusion, although drug resistance
      among untreated Danes was close to the rate estimated in good national
      programmes, close monitoring is needed in future years, as active transmission of
      isoniazid- and streptomycin-resistant Mycobacterium tuberculosis was
      demonstrated.

PMID- 10968493
TI  - Defaulting from tuberculosis treatment in The Netherlands: rates, risk factors
      and trend in the period 1993-1997.
AB  - The aim of this study was to assess the rate of defaulting from treatment among
      tuberculosis patients diagnosed in the Netherlands in the period 1993-1997,
      whether risk groups for defaulting can be identified at the start of treatment
      and the trend of defaulting over time. The Netherlands Tuberculosis Register
      provided data on all patients diagnosed in the Netherlands during the period 1993
      1997. Defaulting probabilities were determined using Kaplan-Meier survival
      analysis and risk factors were identified with Cox's proportional hazard
      analysis. Of 7,529 patients with reported treatment outcome, 718 (10%) defaulted
      or left the country within 1 yr after starting treatment. Defaulting
      probabilities were 9% (95% confidence interval (CI) 8-10%) among 5,256 patients
      in low-risk groups, 17% (95% CI 14-19%) among 1,437 asylum seekers and 29% (95%
      CI 24-34%) among 836 patients in other high-risk groups (other recent immigrants,
      illegal immigrants, the homeless, prisoners and nationals from Eastern Europe).
      Defaulting probabilities decreased over time from 12% in 1993 to 7% in 1997. Risk
      groups for defaulting can be recognized at the start of treatment. The decreasing
      defaulting probabilities were probably due in part to shortening treatment from 9
      to 6 months and improved follow-up of asylum seekers. However, additional
      measures are needed to reduce defaulting among the homeless, recent immigrants,
      illegal immigrants and prisoners.

PMID- 10968494
TI  - Laboratory assessment of fitness to fly in patients with lung disease: a
      practical approach.
AB  - To identify patients with respiratory disease, who may be at risk of developing
      respiratory distress during commercial air travel, a hypoxia inhalation test
      (HIT) can be performed. This paper reports our experience of using such a test
      combined with an interpretation algorithm in a routine respiratory function
      laboratory. Twenty-eight patients were studied. Baseline oxygen saturation
      (Sa,O2) was measured using a pulse oximeter. If Sa,O2 was < 90% no HIT was
      performed and the patient was assessed as unfit for air travel. If baseline Sa,O2
      was > or = 90% an HIT was performed by the patient breathing through a 35%
      Venturi mask supplied with 100% nitrogen which reduced inspiratory oxygen
      fraction to 15.1+/-0.2%. Results were interpreted using a locally derived
      algorithm, and validation was attempted using a questionnaire to investigate
      subsequent symptoms during travel. All patients tolerated the assessment well.
      Twenty-two patients were assessed as "fit to fly" with a further two patients
      "fit to fly with supplemental O2". Four patients were considered unfit to fly.
      Hypoxic response could not be predicted from either forced expiratory volume in
      one second, or pretest saturation. Validation of such protocols is difficult, but
      the hypoxia inhalation test may be a useful tool for predicting hypoxia during
      air travel in patients with chronic respiratory disease.

PMID- 10968495
TI  - Changes in peak expiratory flow indices as a proxy for changes in bronchial
      hyperresponsiveness. Dutch Chronic Non-Specific Lung Disease study group.
AB  - Guidelines for asthma management advocate home peak expiratory flow (PEF)
      monitoring. It is commonly stated that PEF variability is a good proxy of
      bronchial hyperresponsiveness (BHR), a hallmark of asthma. However, this has
      hardly been tested longitudinally, as required to monitor asthma. This study
      assesses which PEF index correlates best with BHR longitudinally and whether the
      correlation improves when correcting PEF values for the known nonlinearity of
      mini-Wright PEF meters. Every 6 months, for a period of 2 yrs, PEF diary cards
      were filled in and BHR to histamine was tested in 104 patients with BHR and
      reversible airways obstruction, who started treatment with bronchodilators with
      (n=33) or without (n=71) inhaled corticosteroids. Within each subject, PEF
      indices and BHR were correlated longitudinally. The highest median correlation
      coefficients were obtained in the group of patients using inhaled
      corticosteroids. The PEF indices providing the best correlation with BHR were:
      mean PEF bronchodilator response (rho=-0.50) and within-day variation (% mean or
      % maximum) (with postbronchodilator values, rho=-0.50; without postbronchodilator
      values, rho=-0.40). Using PEF data corrected for the nonlinearity of the PEF
      meters did not result in higher correlation coefficients. Since current
      guidelines on asthma management recommend only bronchodilators on demand, the
      most useful peak expiratory flow index for reflecting bronchial
      hyperresponsiveness longitudinally is mean within-day peak expiratory flow
      variation (% mean or % maximum) (without postbronchodilator values). Since the
      correlation coefficients are not very strong, the authors suggest that peak
      expiratory flow measurements are not used as a proxy for bronchial
      hyperresponsiveness longitudinally but as a measurement in its own right. The use
      of corrections of peak expiratory flows for the nonlinearity of mini-Wright peak
      expiratory flow meters does not improve the correlation between peak expiratory
      flow and bronchial hyperresponsiveness.

PMID- 10968496
TI  - Optimal asthma control, starting with high doses of inhaled budesonide.
AB  - The aim of this study was to determine whether outcomes in poorly controlled
      asthma can be further improved with a starting dose of inhaled budesonide higher
      than that recommended in international guidelines. The study had a parallel-group
      design and included 61 subjects with poorly controlled asthma, randomized to
      receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks
      (double-blind), then 1,600 microg x day(-1) for 8 weeks (single-blind), followed
      by 14 months of open-label budesonide dose down-titration using a novel
      algorithm, with a written asthma crisis plan based on electronic peak expiratory
      flow monitoring. The primary outcome variable for weeks 1-16 was change in airway
      hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide
      dose. By week 16, there were large changes from baseline in all outcomes, with no
      significant differences between the 3,200- and 1,600-microg x day(-1) starting
      dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak
      flow increased by 134 versus 127 L x min(-1), p=0.8). Subjects starting with
      3,200 microg x day(-1) were 3.8 times more likely to achieve AHR within the
      normal range, as defined by a provocative dose of histamine causing a 20% fall in
      forced expiratory volume in one second (PD20) of > or = 3.92 micromol by week 16
      (p=0.03) [corrected]. During dose titration, there was no significant difference
      in mean budesonide dose (1,327 versus 1,325 microg x day(-1), p>0.3). Optimal
      asthma control was achieved in the majority of subjects (at
      completion/withdrawal: median symptoms 0.0 days x week(-1), beta2-agonist use 0.2
      occasions x day(-1), and PD20 2.4 micromol). In subjects with poorly controlled
      asthma, a starting dose of 1,600 microg x day(-1) budesonide was sufficient to
      lead to optimal control in most subjects. The high degree of control achieved,
      compared with previous studies, warrants further investigation.

PMID- 10968497
TI  - Characterization of exhaled nitric oxide: introducing a new reproducible method
      for nasal nitric oxide measurements.
AB  - Nitric oxide (NO) is present in the human nasal airways and has been suggested to
      originate primarily from the paranasal sinuses. The aim of this study was to
      establish a new and reproducible method for measurement of nasal NO. Through
      repeated single-breath measurements the intra- and inter-individual variations of
      NO levels in nasally (into a tightly fitting mask covering the nose) and orally
      exhaled air were determined in healthy humans. Variations due to the methods used
      were investigated. The contribution of oral NO to the nasal exhalations by
      introducing a mouthwash procedure was also studied. This study shows distinct
      individual values of NO in nasally and orally exhaled air of healthy humans. Some
      diurnal variability was also found with a rise in NO in nasally and orally
      exhaled air over the day, but no, or little, day-to-day variability when
      comparing the results from separate mornings. There was no correlation between NO
      levels in nasally and orally exhaled air, whereas there was a strong correlation
      between NO levels in air exhaled through the left and right nostril. The levels
      of NO in air exhaled at 0.17 L x s(-1) through either nostril separately were
      higher than in air exhaled at the same flow rate through both nostrils
      simultaneously. After the introduction of a mouthwash procedure the level of NO
      in orally, but not nasally exhaled air was reduced. To conclude the method using
      nasal exhalation into a nose mask is highly reproducible. It is also suggested
      that subtracting the level of NO in orally exhaled air, after mouthwash, from
      that in nasally exhaled air, would adequately reflect nasal NO levels.

PMID- 10968498
TI  - Reproducibility of measurements of exhaled NO, and cell count and cytokine
      concentrations in induced sputum.
AB  - Sputum induction is a noninvasive, well-tolerated method for studying airway
      inflammation. When induction with hypertonic saline is repeated at short time
      intervals (<24 h), the cell profile of sputum has not been reproducible. To
      determine the proper interval between sampling cell profiles and cytokine
      contents of sputum samples that had been induced 48 h apart, were compared. In
      addition, the inducible nitric oxide synthase (iNOS) expression of sputum cells
      was compared to the levels of exhaled nitric oxide (NO). Sputum induction and
      measurement of exhaled NO was performed in 31 healthy nonatopic volunteers. Cell
      differentials were counted. Concentrations of interleukin (IL)-4, IL-6, tumour
      necrosis factor (TNF)alpha, eosinophil cationic protein (ECP) were measured in
      sputum supernatant, and iNOS was determined. Reproducibility of cell counts was
      high (r=0.836 total cells, r=0.762 neutrophils, r=0.966 eosinophils, r=0.742
      macrophages). IL-4 (r=0.398), IL-6 (r=0.566), TNFalpha (r=0.658) and ECP
      (r=0.501) were also less reproducible in healthy volunteers. Consistent with the
      low levels of NO in the exhaled air (18.5+/-2.6 ppb and 19.3+/-2.8 parts per
      billion (ppb) on the two study days, r=0.976, p=0.0000), expression of iNOS was
      not detected. In conclusion, in healthy subjects, induced sputum cell counts are
      reproducible. Even though the success rate in nonatopic populations is relatively
      low, sputum induction appears to be a valid method for detecting inflammatory
      changes within the airways, when being performed 48 h apart.

PMID- 10968499
TI  - Muscle metabolic status in patients with severe COPD with and without long-term
      prednisolone.
AB  - Both abnormalities in high energy phosphate metabolism and a decreased oxidative
      enzyme capacity have been reported in skeletal muscle of stable chronic
      obstructive pulmonary disease (COPD) patients. The first aim of this study was to
      investigate whether these findings are present in anterior tibialis muscle and
      whether or not they are associated. Abnormalities in mitochondrial structure and
      function as well as signs of myopathy have been found during corticosteroid
      treatment. The second aim of this study, therefore, was to investigate whether in
      COPD patients prolonged use of low dose prednisolone has effects on muscle energy
      metabolism and qualitative morphology. In a cross-sectional study 15 COPD
      patients (forced expiratory volume in one second (FEV1) 33+/-9 (mean+/-SD) %
      predicted) who were steroid-naive (CORT-) were compared with 10 healthy control
      subjects (HC) and with 14 COPD patients (FEV1 30+/-11 % pred), who had been using
      oral prednisolone for at least 1 yr (CORT+). It was found that adenosine
      triphosphate (ATP)/adenosine diphosphate was lower in CORT- compared to HC (5.7
      versus 6.2, p=0.03). Inosine monophosphate was detected in 13 of 15 CORT-
      compared to 3 of 10 HC (p=0.004). However, although indications were found for an
      imbalance in production and utilization of ATP, comparing CORT- and HC, no
      differences in oxidative (citrate synthase and 3-hydroxy-acyl-coenzyme A
      dehydrogenase) and glycolytic (hexokinase, lactate dehydrogenase and
      phosphofructokinase) enzyme capacities were found. When, comparing steroid
      treated and steroid-naive patient subgroups, no differences in the above
      mentioned parameters of muscle energy metabolism and of muscle qualitative
      morphology were found.

PMID- 10968500
TI  - The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative
      systematic review.
AB  - The role of N-acetylcysteine (NAC) in the treatment of chronic bronchitis is
      unclear. Since a number of studies have been published on this topic, a
      systematic review of published studies seems justified. A systematic search
      (Medline, Embase, Cochrane Library, bibliographies, no language restriction) for
      published randomized trials comparing oral NAC with placebo in patients with
      chronic bronchitis was performed. Dichotomous data on prevention of exacerbation,
      improvement of symptoms and adverse effects were extracted from original reports.
      The relative benefit and number-needed-to-treat were calculated for both
      individual trials and combined data. Thirty-nine trials were retrieved; eleven
      (2,011 analysed patients), published 1976-1994, were regarded as relevant and
      valid according to preset criteria. In nine studies, 351 of 723 (48.5%) patients
      receiving NAC had no exacerbation compared with 229 of 733 (31.2%) patients
      receiving placebo (relative benefit 1.56 (95% confidence interval (CI) 1.37
      1.77), number-needed-to-treat 5.8 (95% CI 4.5-8.1). There was no evidence of any
      effect of study period (12-24 weeks) or cumulative dose of NAC on efficacy. In
      five trials, 286 of 466 (61.4%) patients receiving NAC reported improvement of
      their symptoms compared with 160 of 462 (34.6%) patients receiving placebo
      (relative benefit 1.78 (95% CI 1.54-2.05), number-needed-to-treat 3.7 (95% CI 3.0
      4.9)). With NAC, 68 of 666 (10.2%) patients reported gastrointestinal adverse
      effects compared with 73 of 671 (10.9%) taking placebo. With NAC, 79 of 1,207
      (6.5%) patients withdrew from the study due to adverse effects, compared with 87
      of 1,234 (7.1%) receiving placebo. In conclusion, with treatment periods of
      approximately 12-24 weeks, oral N-acetylcysteine reduces the risk of
      exacerbations and improves symptoms in patients with chronic bronchitis compared
      with placebo, without increasing the risk of adverse effects. Whether this
      benefit is sufficient to justify the routine and long-term use of N
      acetylcysteine in all patients with chronic bronchitis should be addressed in
      further studies and cost-effectiveness analyses.

PMID- 10968501
TI  - Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD
      patients: influence of flow pattern.
AB  - In mechanically ventilated patients the flow pattern during bronchodilator
      delivery by metered-dose inhaler (MDI) could be a factor that might influence the
      effectiveness of this therapy. In order to test this the effect of two different
      inspiratory flow patterns on the bronchodilation induced by beta2-agonists
      administered via MDI and spacer in a group of mechanically ventilated patients
      with chronic obstructive pulmonary disease (COPD) was examined. Eighteen
      mechanically ventilated patients with COPD, were prospectively randomized to
      receive two (n=8, protocol A) or six (n=10 protocol B) puffs salbutamol (100
      microg x puff(-1)) either under pressure control (decelerating flow pattern) or
      under volume control (square wave flow pattern). With both modes, tidal volume
      and inspiratory time were identical. Salbutamol was administered via an MDI
      adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud
      enhancer spacer. After a 6-h washout, patients were crossed over to receive the
      same dose of salbutamol (200 or 600 microg, respectively in protocols A and B) by
      the alternative mode of administration. Static and dynamic airway pressures,
      minimum (Rint) and maximum (Rrs) inspiratory resistance and the difference
      between Rrs and Rint (deltaR) were measured before and at 15, 30 and 60 min after
      salbutamol. Independent of the dose, salbutamol caused a significant decrease in
      dynamic and static airway pressures, Rint and Rrs. These changes were not
      influenced by the inspiratory flow pattern and were evident at 15, 30 and 60 min
      after salbutamol. It is concluded that salbutamol delivered via metered dose
      inhaler and spacer device, induces significant bronchodilation in mechanically
      ventilated patients with chronic obstructive pulmonary disease, the magnitude of
      which is not affected by the inspiratory flow/time profile.

PMID- 10968502
TI  - Role of inspiratory capacity on exercise tolerance in COPD patients with and
      without tidal expiratory flow limitation at rest.
AB  - Expiratory flow limitation promotes dynamic hyperinflation during exercise in
      chronic obstructive pulmonary disease (COPD) patients with a consequent reduction
      in inspiratory capacity (IC), limiting their exercise tolerance. Therefore, the
      exercise capacity of patients with tidal expiratory flow limitation (FL) at rest
      should depend on the magnitude of IC. The presented study was designed to
      evaluate the role of FL on the relationship between resting IC, other respiratory
      function variables and exercise performance in COPD patients. Fifty-two patients
      were included in the study. Negative expiratory pressure (NEP) uptake (VO2,max)
      were measured during an incremental symptom-limited cycle exercise. Twenty-nine
      patients were FL at rest. The IC was normal in all non-FL patients, while in most
      FL subjects it was decreased. Both WRmax and VO2,max were lower in FL patients
      (p<0.001, each). A close relationship of WRmax and O2,max to IC was found (r=0.73
      and 0.75, respectively; p<0.0001, each). In the whole group, stepwise regression
      analysis selected IC and forced expiratory volume in one second (FEV1)/forced
      vital capacity (FVC) (% predicted) as the only significant contributors to
      exercise tolerance. Subgroup analysis showed that IC was the sole predictor in FL
      patients, and FEV1/FVC in non-FL patients. Detection of flow limitation provides
      useful information on the factors that influence exercise capacity in chronic
      obstructive pulmonary disease patients. Accordingly, in patients with flow
      limitation, inspiratory capacity appears as the best predictor of exercise
      tolerance, reflecting the presence of dynamic hyperinflation.

PMID- 10968503
TI  - Diffusion capacity and haemodynamics in primary and chronic thromboembolic
      pulmonary hypertension.
AB  - The transfer factor of the lung for carbon monoxide (TL,CO) is decreased in
      patients with pulmonary hypertension. The pulmonary membrane diffusion capacity
      (Dm) and pulmonary capillary blood volume (Vc), were studied to establish: 1) the
      relative contribution of the components of the transfer factor to the decrease in
      TL,CO; 2) whether differences exist between primary pulmonary hypertension (PPH)
      and chronic thromboembolic pulmonary hypertension (CTEPH); and 3) the
      relationship between these parameters and haemodynamic parameters. Dm and Vc were
      determined in 19 patients with PPH and in eight patients with CTEPH. The patients
      had been referred for consideration for lung transplantation. Haemodynamic
      parameters were assessed by heart catheterization. In the PPH group, Vc was
      reduced in 12 of 19 patients (mean+/-SD Vc 72+/-14% of the predicted value) and
      Dm in 17 of 19 patients (60+/-22% pred). In the CTEPH group, Vc was reduced in
      six of eight patients and Dm in seven of eight patients. The mean TL,CO Dm and Vc
      values were similar to those in the PPH group. The reduction in pulmonary
      membrane diffusion capacity was significantly greater than that in pulmonary
      capillary blood volume. No differences in pulmonary and cardiovascular functional
      values were found between the groups. Right atrial pressure showed a significant
      negative correlation with pulmonary capillary blood volume and an increased
      pulmonary vascular resistance was associated with a decrease in pulmonary
      membrane diffusion capacity. These results suggest pronounced functional
      impairment of the alveolocapillary membrane in these patients.

PMID- 10968504
TI  - Pulmonary artery pressure measurement during exercise testing in patients with
      suspected pulmonary hypertension.
AB  - It is recognized that exercise produces abnormally large increases in pulmonary
      artery pressure in patients with pulmonary vascular disease as a consequence of a
      variety of disorders, but the relationship between pressure and cardiopulmonary
      exercise performance is poorly understood. This lack of understanding is due (in
      part) to difficulty making measurements of pulmonary haemodynamics using
      conventional fluid filled catheters. This article seeks to improve understanding
      by comparing variables measured during formal exercise testing with simultaneous
      measurements of pulmonary artery pressure using a micro-manometer tipped
      catheter. Ten patients with suspected pulmonary hypertension were studied using a
      micromanometer tipped pulmonary artery catheter, during cardiopulmonary exercise
      testing. Ventilatory equivalents for oxygen and carbon dioxide correlated with
      the pulmonary artery pressure measured on exercise, but oxygen pulse and oxygen
      uptake did not. Ventilatory equivalents, noninvasively measured during exercise,
      may merit further study as potential surrogates of pulmonary artery pressure and
      hence be useful in identifying individuals at risk of developing pulmonary
      hypertension.

PMID- 10968505
TI  - Pulmonary NO synthase inhibition and inspired CO2: effects on V'/Q' and pulmonary
      blood flow distribution.
AB  - Inhaled carbon dioxide decreases ventilation/perfusion ratio (V'/Q')
      heterogeneity in dogs. The aim of this study was to test whether inhaled CO2
      improves the V'/Q' by inhibition of nitric oxide production and whether
      inhibition of endogenous NO production in the lung alters gas exchange and V'/Q'
      matching. Eleven healthy dogs were anaesthetized and mechanically ventilated. The
      multiple inert gas elimination technique (MIGET) was used to measure V'/Q'
      heterogeneity and regional pulmonary blood flow heterogeneity was assessed in
      five dogs using fluorescent microspheres. In a separate set of five dogs, exhaled
      NO levels were measured via chemiluminescence. All dogs were studied before and
      after 4.8% inspired CO2, and then given the NO synthase inhibitor N(omega)-nitro
      L-arginine methyl ester (L-NAME, 10 mg x kg(-1)) via nebulization, after which
      they were studied again with room air and inhaled CO2. CO2 and L-NAME improved
      arterial and alveolar oxygen tension, but the improvements with L-NAME did not
      reach statistical significance. Improved V'/Q' matching, as assessed by the
      MIGET, occurred under all experimental conditions. Exhaled NO levels were reduced
      by 40% with CO2 and 70% with L-NAME. The standard deviation of regional pulmonary
      blood flow assessed via microspheres decreased only with inhaled CO2. Fractal
      analysis of pulmonary blood flow distributions revealed that regional blood flow
      was highly correlated with flow to neighbouring pieces of lung in all four
      conditions with no changes in the fractal dimension. Inspired carbon dioxide
      improves ventilation perfusion ratio matching and is associated with a more
      homogeneous distribution of pulmonary blood flow. Although inspired carbon
      dioxide causes a reduction in exhaled nitric oxide, the differences in pulmonary
      perfusion distributions found between carbon dioxide and N(omega)-nitro-L
      arginine methyl ester suggest that the carbon dioxide effect is not mediated by a
      reduction in nitric oxide production. The improved ventilation perfusion ratio
      matching with inhibition of nitric oxide synthase suggests the intriguing
      possibility requiring further study that endogenous production of nitric oxide in
      the lung does not subserve ventilation perfusion ratio regulation.

PMID- 10968506
TI  - Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of
      ventilator-associated bronchopneumonia.
AB  - The study was designed to identify markers of oxidative injury, related to the
      nitric oxide derived cascade, in bronchoalveolar lavage (BAL) fluid from
      intensive care patients suspected of ventilator-associated pneumonia (VAP) and/or
      acute respiratory distress syndrome (ARDS). Thirty-eight patients developing VAP
      and/or ARDS (VAP/ARDS group) were compared to 20 ventilated patients without
      VAP/ARDS (control group). Myeloperoxidase (MPO) and elastase, taken as markers of
      neutrophil activation were measured by enzymatic techniques, and nitrated
      proteins (NTPs) by an immunological method. The cytotoxicity of the BAL fluid was
      tested using cultured human epithelial alveolar cells by the release of pre
      incorporated 51Cr. Mean NTP concentration and, MPO and elastase activities were
      different between the VAP/ARDS and control groups (p<0.05 for NTPs; p<0.005 for
      MPO; p<0.005 for elastase). NTP concentration correlated with MPO and elastase
      activity and neutrophil number (r=0.93, 0.91 and 0.87, respectively), but not to
      protein concentration and arterial oxygen tension/inspiratory oxygen fraction.
      The cytotoxicity of BAL correlated with NTP concentration (r=0.92) and MPO
      activity (r=0.89). It was concluded that the concentrations of nitrated proteins
      in bronchoalveolar lavage fluid correlated with the oxidant activity of
      neutrophils and that, bronchoalveolar lavage fluid cytotoxicity was correlated
      with the nitrated protein concentration and may be mediated by oxidants.

PMID- 10968507
TI  - Bedside assessment of respiratory viscoelastic properties in ventilated patients.
AB  - Viscoelasticity represents an important component of respiratory mechanics, being
      responsible, in some cases, for most of the pressure dissipated during breathing.
      Hitherto the methods available for determining the viscoelastic properties have
      been simplified, but are still time-demanding and depend on a great deal of
      calculation. In this study, a simple means of determining respiratory
      viscoelastic properties during mechanical ventilation was introduced. The
      viscoelastic constants of the respiratory system, modelled as a Maxwell body,
      were studied in 17 normal subjects and seven patients with acute lung injury
      (ALI) using two end-inspiratory occlusions; one with a short inspiratory time
      (tI) to determine the elastic component of viscoelasticity and the other with a
      long tI to assess the resistive component of viscoelasticity. The results were
      reproducible and similar to those provided by the previously described multiple
      breath method (MB). The mean+/-SD viscoelastic resistance was 5.31+/-1.50 cm H2O
      x L(-1) x s with the proposed method and 5.71+/-1.87 cm H2O x L(-1) x s with the
      MB method in normal subjects, and 8.93+/-2.82 cm H2O x L(-1) x s and 10.36+/-3.13
      cm H2O x L(-1), respectively in ALI patients. The mean+/-SD viscoelastic
      elastance was 3.92+/-0.84 cm H2O x L(-1) and 4.94+/-1.01 cm H2O x L(-1) in normal
      subjects and 7.08+/-2.01 cm H2O x L(-1) and 8.21+/-1.16 cm H2O x L(-1) in ALI
      patients, respectively. The mean+/-SD viscoelastic time constant was 1.36+/-0.24
      s and 1.17+/-0.34 s in normal subjects and 1.26+/-0.35 s and 1.24+/-0.23 in ALI
      patients, respectively. The method was easy to perform and applicable at the
      bedside in clinical routine.

PMID- 10968508
TI  - Dermatophagoides pteronyssinus and bioelectric properties of airway epithelium:
      role of cysteine proteases.
AB  - Several epidemiological studies suggest that exposure to house dust mite
      allergens plays a role in the pathogenesis of asthma. Since many of these
      allergens exhibit enzymatic properties, they may damage the airway epithelium. To
      characterize the effects of low doses of Dermatophagoides pteronyssinus on the
      airway epithelium, the effect of D. pteronyssinus on the epithelial bioelectric
      properties of tracheal fragments of non-sensitized Lewis rats was studied, using
      Ussing-type chamber technique. The addition of a crude D. pteronyssinus extract
      containing 20 microg mL(-1) of Der pI allergen in the presence of 1.5 mM
      dithiothreitol (DTT, an activator of cysteine proteases), induced a progressive
      increase in bioelectrical conductance (+12.0+/-1.5%, n=12, p<0.005), an index of
      epithelial permeability, without affecting the short circuit current (which
      reflects active ion transports). The D. pteronyssinus-induced increase in
      epithelial conductance was related to the cysteine-protease activity of the
      allergen since it was not observed in the absence of DTT (n=12), and was
      completely suppressed in the presence of 10 nM E-64, a specific inhibitor of
      cysteine proteases (n=12). D. pteronyssinus-induced increase in epithelial
      conductance could be entirely attributed to an increase in the paracellular
      conductance (+11.2+/-1.2%, n=8, p<0.01). There was no electrophysiological
      evidence of rupture in epithelial continuity, and no cell detachment was observed
      on microscopic examination. In conclusion, the cysteine protease activity of
      crude Dermatophagoides pteronyssinus extract is able to increase the epithelial
      paracellular conductance of rat tracheal tissues, even at relatively low doses
      that do not induce cell detachment or cell death.

PMID- 10968509
TI  - Effects of the thromboxane receptor agonist U46619 and endothelin-1 on large and
      small airways.
AB  - Recently attention has been drawn to the role of small airways in asthma.
      However, little information exists about the responsiveness of small airways to
      various bronchoconstrictors in comparison to large airways. In this study, the
      model of precision-cut lung slices (PCLSs) was used to investigate the effects of
      the thromboxane receptor agonist U46619 and endothelin (ET)-1 on small (diameter
      <250 microm), medium (250-420 microm) and large (>420 microm) airways. Viable
      PCLSs were prepared from rat lungs and the bronchoconstriction of differently
      sized airways inducible by U46619 and ET-1 was observed by means of a microscope
      and analysed by digital imaging techniques. The median effective concentration
      (EC50) of U46619 for inducing bronchoconstriction was 6.9 nM in small and 66 nM
      in large airways, respectively. This finding was corroborated by direct
      observations in single lung slices containing both a small and a large airway. In
      such slices, U46619 caused smaller airways to contract to a greater degree than
      larger ones. ET-1 induced bronchoconstriction was similar in small (EC50 34 nM)
      and in medium or large (ECso 22 nM) airways. This was again confirmed by direct
      observation of ET-1-treated PCLSs. It is concluded that, in rat lungs, endothelin
      1 affects small and large airways to the same extent, whereas thromboxane is ten
      times more potent in causing small airways to contract than larger ones.
      Precision-cut lung slices appear to be a valuable model for examining the
      (patho)physiology of small airways.

PMID- 10968510
TI  - Flow cytometric analysis of the effect of dithiothreitol on leukocyte surface
      markers.
AB  - Pretreatment with dithiothreitol (DTT) is necessary to dissolve mucus in samples
      of induced sputum prior to analysis. However, DTT may affect cell surface markers
      which are essential for lymphocyte subtyping. Therefore, the aim of this study
      was to evaluate the effect of DTT on an appropriate panel of surface markers.
      Peripheral blood leukocytes were used because these cells, in contrast to sputum
      cells, could be obtained without DTT treatment. Peripheral blood from healthy
      donors was incubated with either DTT according to standard sputum procedures or
      phosphate-buffered saline (PBS), washed and incubated with fluorochrome-labelled
      antibodies. After lysis of erythrocytes, analysis was performed using a
      calibrated flow cytometer. Leukocyte populations were identified by their light
      scattering properties. For analysis, fluorescence intensity was compared between
      DTT- and PBS-treated samples. After treatment with DTT, fluorescence intensity
      was significantly increased in CD16-positive granulocytes; it was reduced in CD2
      positive lymphocytes, CD45-positive lymphocytes and CD14-positive monocytes (p <
      or = 0.001). These changes occurred in all samples. The fluorescence intensity of
      CD3-, CD4-, CD8-, CD19-, CD56- and histocompatibility leukocyte antigen DR
      positive lymphocytes was not altered by DTT. However, there were statistically
      significant (p<0.001), although small, changes in the percentages of leukocytes.
      The present data demonstrate that, although dithiothreitol as used in sputum
      analysis affects some surface markers of peripheral blood leukocytes,
      comparability between samples concerning lymphocyte surface markers is preserved.
      Therefore, it is suggested that treatment of sputum samples with dithiothreitol
      does not invalidate the immunocytochemical analysis of lymphocytes.

PMID- 10968511
TI  - Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus
      in some human lung tumours.
AB  - Human bronchioloalveolar carcinoma (BAC) is a lung cancer, morphologically
      similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary
      adenomatosis (SPA) or jaagsiekte. SPA is caused by an exogenous type B/D
      retrovirus (jaagsiekte sheep retrovirus (JSRV)), which prompted the present study
      to obtain evidence of a retrovirus in BAC. A panel of 249 human lung tumours, 21
      nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other
      organs and a cell line expressing a human endogenous retrovirus protein was
      examined immunohistochemically using a rabbit antiserum directed against the JSRV
      capsid protein. Specific staining was detected only in the cytoplasm of
      recognizably neoplastic cells in the pulmonary alveoli of 39 of 129 (30%) BACs,
      17 of 65 (26%) lung adenocarcinomas and two of seven large cell carcinomas. The
      remaining samples were negative. These results support the hypothesis that some
      human pulmonary tumours may be associated with a jaagsiekte sheep retrovirus
      related retrovirus, warranting further studies.

PMID- 10968512
TI  - Enhancing care for people with asthma: the role of communication, education,
      training and self-management. 1998 World Asthma Meeting Education and Delivery of
      Care Working Group.
AB  - Reduction in the morbidity associated with asthma requires attention to several
      aspects of the behaviour of health professionals and patients, and to the
      interactions between these two groups. In this review, what has been learnt about
      health professional/patient communication and patient education (skills, settings
      and materials), lay and health professional liaison (including telephone
      helplines), patient education in low-income countries, the integration of patient
      education into clinical practice, health professional training and the
      implementation of guidelines, and the role of national asthma campaigns is drawn
      together. What changes in public policy would enhance asthma care, and whether
      the promotion of asthma self-management skills is cost effective are also
      considered. It is concluded that, although further research is necessary in many
      areas, well-educated health professionals who recognize the person with asthma as
      an individual, and who give advice about self-management, can significantly
      reduce the suffering and costs associated with asthma.

PMID- 10968513
TI  - The contribution of airway smooth muscle to airway narrowing and airway
      hyperresponsiveness in disease.
AB  - Airway hyperresponsiveness (AHR), the exaggerated response to constrictor
      agonists in asthmatic subjects, is incompletely understood. Changes in either the
      quantity or properties of airway smooth muscle (ASM) are possible explanations
      for AHR. Morphometric analyses demonstrate structural changes in asthmatic
      airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy,
      neovascularization and an increase in ASM mass. Mathematical modelling of airway
      narrowing suggests that, of all the changes in structure, the increase in ASM
      mass is the most probable cause of AHR. An increase in ASM mass in the large
      airways is more closely associated with a greater likelihood of dying from asthma
      than increases in ASM mass in other locations within the airway tree. ASM
      contraction is opposed by the elastic recoil of the lungs and airways, which
      appears to limit the degree of bronchoconstriction in vivo. The cyclical nature
      of tidal breathing applies stresses to the airway wall that enhance the
      bronchodilating influence of the lung tissues on the contracting ASM, in all
      probability by disrupting cross-bridges. However, the increase in ASM mass in
      asthma may overcome the limitation resulting from the impedances to ASM
      shortening imposed by the lung parenchyma and airway wall tissues. Additionally,
      ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a
      greater degree of bronchoconstriction when stimulated to contract than slower
      ASM. Changes in ASM properties are induced by the process of sensitization and
      allergen-exposure such as enhancement of phospholipase C activity and inositol
      phosphate turnover, and increases in myosin light chain kinase activity. Whether
      changes in ASM mass or biochemical/biomechanical properties form the basis for
      asthma remains to be determined.

PMID- 10968514
TI  - Update on sputum methodology.
AB  - Over the past few years cellular and biochemical sputum examinations have become
      important instruments to assess airway inflammation. The aim of this review is to
      summarize new methodological developments and aspects, which are currently under
      investigation. The use of isotonic saline has increased safety of inductions in
      patients with severe asthma and in children. The origin of sputum is better
      understood, as is the need to standardize the volume and duration of induction.
      It also needs to be borne in mind that the induction procedure itself is able to
      cause changes in sputum composition. However, the basic induction and processing
      procedures have not changed much over the last few years, and therefore the
      method is still time consuming. The analysis of ECP in lysed sputum cells as a
      marker for the number of eosinophils has been suggested to overcome this problem,
      but needs further validation. Furthermore, storage of sputum has been studied, as
      well as early fixation or freezing of sputum cells to elongate the time between
      induction and processing. Differential cell counts by flow cytometry are still
      difficult, but the method has increased knowledge concerning lymphocyte subsets
      and the activation status of sputum cells. The use of induced sputum to
      noninvasively measure airway inflammation in clinical trials will offer
      additional information, but the proper use and interpretation of sputum outcome
      parameters will need further investigation.

PMID- 10968515
TI  - "Coffee grounds" through the chest tube.

PMID- 10968517
TI  - Is lung function really a good parameter in evaluating the long-term effects of
      inhaled corticosteroids in COPD?

PMID- 10968516
TI  - Standardization of antituberculosis drug resistance surveillance in Europe.
      Recommendations of a World Health Organization (WHO) and International Union
      Against Tuberculosis and Lung Disease (IUATLD) Working Group.
AB  - Surveillance of antituberculosis drug resistance is an essential tool for
      evaluating the quality of tuberculosis control programmes. Consensus-based
      recommendations on uniform reporting of antituberculosis drug resistance
      surveillance data in Europe have been developed by a Working Group of the World
      Health Organization (WHO) and the International Union Against Tuberculosis and
      Lung Disease (IUATLD). Laboratories should use standardized methods for testing
      drug susceptibility with a quality assurance programme including national and
      international proficiency testing. The proportion of drug resistance,
      particularly resistance to isoniazid, rifampicin or both (multidrug resistance)
      among all definite, i.e. culture-positive, tuberculosis cases at the start of
      treatment is the major indicator of interest. It should be calculated separately
      among patients treated previously and among those who have never been treated
      with > or = 1 month of combined antituberculosis drugs. The Working Group
      recommends that, in countries in which resources allow, laboratories report drug
      susceptibility test results on all isolates of the Mycobacterium tuberculosis
      complex. Test results of the specimen at the start of treatment and clinical data
      from the notification should be linked using a suitable identifier. Results
      should be presented by calendar year and analysed by age, sex, place of birth,
      site of disease and sputum smear results. In countries in which a routine system
      cannot be organized, representative surveys or sentinel systems are possible
      alternatives. In some countries, the annual prevalence of multidrug-resistant
      tuberculosis may be estimated through a national laboratory reporting system.

PMID- 10968518
TI  - Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics
      with allergic rhinitis.

PMID- 10968519
TI  - Diagnostic utility of eosinophils in pleural fluid.

PMID- 10968520
TI  - Postoperative ambulatory level after hip fracture in the elderly predicts
      survival rate.
AB  - The purpose of this study was to evaluate whether the ambulatory level premorbid
      or at discharge reflected the survival rate better. Ambulatory level was
      retrospectively evaluated as a postoperative indicator of survival rate following
      operative treatment in 301 consecutive patients over 65 years old. All of the
      patients were followed up for a mean of 62 months. The postoperative ambulatory
      level at discharge reliably reflected the survival rate in the elderly after hip
      fracture, better than the premorbid ambulatory level. It is confirmed that the
      planning of the operation and rehabilitation to maintain the premorbid ambulatory
      level after hip fracture might be critical.

PMID- 10968521
TI  - Multiple epiphyseal dysplasia--report of two families.
AB  - Multiple epiphyseal dysplasia (MED) is a relatively uncommon inherited disorder
      of epiphyseal maturation. Affected individuals may have a degree of short-limbed
      dwarfism, short stubby digits, and stiff or painful joints. We report two
      families of MED and emphasize the variations of joint involvement. Ten out of 34
      members in family A and 13 out of 39 members in family B were suspected of having
      MED by questionnaire. Radiological examination was done for 3 out of the 10
      members in family A and 6 out of the 13 members in family B. In both families,
      the epiphyseal disturbances in the skeleton were bilaterally symmetric and
      involved several joints. Apparent dwarfism, short stubby digits and spinal
      involvement were not observed. The degree and the pattern of affected joints were
      different in the two families and even among members of the same family. In
      family A, the knee joint was commonly affected, followed by the ankle joint. The
      deformity of the joints was mild and caused only slight disability. No apparent
      hip lesion was present. In family B, the hip joint was predominantly affected,
      followed by the knee and ankle joints, and the deformity was severer than that in
      family A. These observations suggest that MED is a group of heterogeneous
      disorders.

PMID- 10968522
TI  - Rotational acetabular osteotomy for severely dysplastic acetabulum.
AB  - The operative procedures chosen for arthrosis with severe acetabular dysplasia
      vary among orthopaedic surgeons. We operated on 250 hips using the rotational
      acetabular osteotomy (RAO) method of Ninomiya and Tagawa [8]. In this report, we
      describe the technique of RAO and the results of this procedure in patients with
      severely dysplastic hips. Among the 250 hips, there were 6 which were classified
      as Severin group V. In those hips, the CE angle was less than 0 degrees, and the
      femoral head showed superolateral subluxation. After acetabular osteotomy with
      straight and curved osteotomes, smooth inferolateral rotation could be done in
      all cases. At the latest follow-up symptoms were improved remarkably, especially
      pain. Radiographically, adequate coverage of the femoral head was achieved and
      joint congruence improved in all 6 hips.

PMID- 10968523
TI  - Radiographic analysis of lumbar spine for low-back pain in the general
      population.
AB  - We sought to demonstrate a correlation between low-back pain (LBP) and the plain
      radiographic findings of the lumbar spine in the general population based on an
      analysis of 838 persons, 387 of whom presented with complaints of low-back pain.
      The incidence of intervertebral narrowing and irregular ossification of the
      vertebral end-plate image increased consistently with age and was higher in the
      presence of LBP in any age or gender group. Multiregression analysis was
      performed with the imaging factors as multivariates. As a result, multiregression
      equations with irregular ossification of the vertebral end-plate image,
      intervertebral narrowing, spondylolisthesis and abnormal lumbar lordotic angle
      combined as variates showed the highest significance as predictors of a
      relationship with LBP. The discrimination analysis was performed using the linear
      discriminant function, resulting in a true discrimination rate of 65%. Plain
      radiography of the lumbar spine is thus significant as it provides information
      which can be evaluated as meaningful findings in the investigation of LBP. In
      addition, while the significance can be increased by considering multiple
      factors, it is important to understand the limits of the accuracy of this
      prediction.

PMID- 10968524
TI  - Cemented femoral impaction bone grafting for severe osteolysis in revision hip
      arthroplasty. Good results at 4-year follow-up of 10 patients.
AB  - Ten hips underwent impaction bone grafting with cement as revision of the femoral
      stem for severe osteolysis. At clinical follow-up of a median of 4 years (range
      3.0-4.6 years) there were no failures. The median Harris hip score increased from
      53 to 80, and pain score from 25 to 40. Radiographically, there was no resorption
      of the impacted grafts. All of the 9 patients with radiographical follow-up of
      more than 1 year showed trabecular remodelling, 7 of whom had signs of cortical
      repair. Subsidence was a median of 2 mm, with the maximum subsidence being 5 mm.
      The results appeared clinically stable after 4 years with radiographic
      reconstitution of the bone stock.

PMID- 10968525
TI  - Magnetic resonance imaging of growth plate injuries: the efficacy and indications
      for surgical procedures.
AB  - In 23 patients with growth plate injuries, magnetic resonance imaging (MRI)
      studies were performed a total of 31 times to evaluate the physis which showed
      plain radiographic evidence of possible damage. Fourteen patients clinically
      showed growth arrest, and 10 patients required a Langenskiold operation. In 3
      patients who underwent this operation, subsequent premature total fusion of the
      physis adversely affected the postoperative results. We propose that the merging
      shape of the arrest line with calcification of the provisional zone of the
      metaphysis shown by MRI indicates poor viability of the physis. MRI provided
      useful information on the appearance of the growth plate and changes in the
      metaphysis, both of which affected the prognosis and the results of the surgical
      procedures.

PMID- 10968526
TI  - Moderate to severe hallux valgus deformity: correction with proximal crescentic
      osteotomy and distal soft-tissue release.
AB  - Between 1991 and 1995, 96 patients (114 feet) were treated with a proximal
      crescentic metatarsal osteotomy and distal soft-tissue procedure for moderate to
      severe hallux valgus deformity [intermetatarsal (IM) angle > 15 degrees, or
      hallux valgus (HV) angle > 30 degrees]. At an average follow-up of 26 months, 8
      men and 62 women (86 feet) with a mean age of 53.2 years were retrospectively
      reviewed. The HV angle averaged 41.1 degrees preoperatively and 14.6 degrees
      postoperatively. The respective values for the IM angle were 17.8 degrees and 7.8
      degrees. Neither the average metatarsal shortening of 3 mm nor the dorsal
      angulation at the osteotomy site seen in 9% of cases evidenced any clinical
      significance at follow-up. Patient satisfaction was excellent or good in 91%, and
      the mean Mayo Clinic Forefoot Score (total 75 points) improved from 37.2 to 61.1
      points. Complications included 8 cases of hallux varus and 5 cases of hardware
      failure. Based on this first study exclusively focusing on moderate to severe
      hallux valgus deformity, we conclude that proximal first metatarsal osteotomy in
      combination with a lateral soft-tissue procedure is effective in correcting
      moderate to severe symptomatic hallux valgus deformity with metatarsus primus
      varus (IM angle > 15 degrees or HV angle > 30 degrees).

PMID- 10968527
TI  - The effect of extracorporeal shock waves on joint cartilage--an in vivo study in
      rabbits.
AB  - The application of extracorporeal shock waves has become a new mode of treatment
      for affections of the locomotor apparatus such as calcifying tendinitis,
      epicondylitis humeri radialis, calcaneodynia and pseudarthrosis. The treatment
      often takes place in the vicinity of joints. Up to now no systematic data have
      been published about possible side-effects on joint cartilage. In an in vivo
      study the effect of extracorporeal shock waves on joint cartilage was evaluated
      in 24 immature New Zealand White rabbits. The left lateral femoral condyle of
      each animal was treated with 2000 shock waves of 1.2 mJ/mm2; the right condyle
      served as control. Macroscopical, radiological and histological analysis at 0, 3,
      12 and 24 weeks after treatment showed no pathological changes in the joint
      cartilage. We conclude that extracorporeal shock wave treatment does not cause
      damage to the joint cartilage of growing rabbits.

PMID- 10968528
TI  - Total hip arthroplasty using an uncemented femoral component with taper design:
      outcome at 10-year follow-up.
AB  - The aim of this study was to assess the clinical and radiological outcome of the
      cementless-system (CLS) femoral component designed by Spotorno with a taper
      design. Ninety-four patients (107 hips) were operated on from January 1987 to
      December 1988. The female/male ratio was 2/1, the mean age was 51 years (range 20
      77 years). Clinical follow-up was obtained in 89 hips (83%). Five patients (7
      hips, 6.5%) could not be traced. Nine patients (11 hips, 10%) had died before the
      minimum time of follow-up required for this study (10 years). All these hips
      still had their stem in place at the time of the last intermediate inquiry. The
      mean follow-up was 10.3 +/- 0.3 years. No stem required revision. According to
      the Harris score, 84% of hips were rated good or excellent, 14% fair, and 2%
      poor. The average Harris hip score was 88 at the time of the last follow-up.
      Fifteen patients (17%) reported occasional thigh pain. All patients reported
      complete relief of pain within the first 6 months after the operation.
      Radiologically, 95% of stems showed stable fixation by bony ingrowth, 5% by
      fibrous ingrowth. Seven (9%) uncemented acetabular components showed progressive
      migration. Three of those cups had been replaced in the meantime. Fifty-one (65%)
      of the CLS stems induced either no change in femoral bone density or only patchy
      loss of bone density localized to zone 1 or 7 according to Gruen, while 27 (35%)
      of the hips showed some reduction of bone density in the proximal diaphysis of
      the femur (zone 2 or 6). Severe progressive osteolysis of the femoral cortex
      underneath the lesser trochanter was found in 4 hips (5%) with coexistent
      loosening of the cup. In all of these hips, the Mecron cup had been used. At a
      mean follow-up of 10 years, the results of the CLS femoral component are
      comparable with those of modern techniques of cementing in primary total hip
      arthroplasty and with the long-term outcomes of other uncemented stems with
      tapered design. The long-term fixation of the cup remains an unsolved problem.

PMID- 10968529
TI  - Do Colles' fracture patients benefit from routine referral to physiotherapy
      following cast removal?
AB  - Colles' fracture patients who received physiotherapy immediately following cast
      removal were compared with patients who received no active therapy following cast
      removal in a prospective randomised study. Patients who attended physiotherapy
      achieved significantly greater increases in wrist extension and grip strength
      after 6 weeks compared to patients who received no active therapy.

PMID- 10968530
TI  - Scintigraphic evaluation of impaction grafting for total hip arthroplasty
      revision.
AB  - To determine the fate of an impacted allograft after a minimum follow-up of 1
      year, we examined 9 of 40 patients who underwent revision arthroplasty with the
      impaction grafting technique. The allograft used in this study was morselized
      cancellous freeze-dried allograft. We examined these 9 patients with technetium
      99 m methylene diphosphonate bone scintigraphy at an average of 14 (range 12-20)
      months after surgery. All of them had a good clinical outcome, with an average
      postoperative Hip Society Score of 89 (range 65-98) and no evidence of
      radiolucency or subsidence on direct radiography. Scintigraphic examination
      demonstrated that the area corresponding to the allograft had a remarkable
      radioactivity accumulation suggesting new bone formation. The allograft in total
      hip revision using the impaction grafting technique undergoes a significant
      neovascularization and new bone formation. This study suggests than when vigorous
      impaction is used, freeze-dried cancellous allograft can be used for impaction
      grafting.

PMID- 10968531
TI  - Cubitus varus: problem and solution.
AB  - A lateral closing wedge osteotomy was performed in 39 children with cubitus varus
      deformity resulting from a supracondylar fracture. All had a deformity of 15
      degrees or more, with 5 having more than 30 degrees of varus. The osteotomy was
      fixed by three different methods. In 8 cases the osteotomy was fixed with 2
      parallel Kirschner wies (group K). A modified French technique (group TBW) was
      used in 25 cases and held with a figure-of-8 wire loop tightened over the screw
      heads. In the last 6 cases the osteotomy was fixed with an external fixator
      (group EF). The only poor result (i.e. loss of carrying angle of more than 10
      degrees and loss of flexion and extension of 20 degrees or more) was in group K
      due to pin tract infection and loosening of the K-wires. In the TBW group 5
      patients lost some degree of correction, and none became infected. In the EF
      group no patient suffered pin tract infection or loss of correction. Based on our
      experience and results, we feel that the best age at which to correct cubitus
      varus deformity was 6-11 years and that the external fixator is a safe, effective
      and reliable method to fix the osteotomy. We propose this method of fixation as a
      good alternative method to the modified French technique, especially in cases of
      severe cubitus varus deformity, where removal of a large wedge can produce a big
      step at the osteotomy site, increasing the possibility of disengagement of the
      stainless steel wire from the screw head. In addition, minor postoperative
      modifications of correction, if required, can also be performed. It also avoids a
      second operation for implant removal.

PMID- 10968532
TI  - Functional outcome of transplanted knee joints in dogs.
AB  - Total knee joint transplantation has been performed in animal models and humans.
      This study investigates the impact of this operation on knee joint function in a
      dog model. Therefore, replantation was compared to transplantation during a 6
      month follow-up period in four dogs in each group. The peak vertical ground
      reaction force normalized in all legs undergoing replantation and in two of four
      after transplantation. A third transplant recipient reduced loading from the 4th
      month due to a local complication, and the fourth succumbed to sepsis 3 months
      postoperatively. A weight-bearing index (WBI), defined as loading of the grafted
      divided by loading of both hind-limbs decreased from 0.48 +/- 0.08 preoperatively
      to 0.13 +/- 0.10 by 1 month after replantation and from 0.53 +/- 0.07 to 0 after
      transplantation. After 6 months, weight-bearing of all replant recipients was
      restored, but reduced in two transplant recipients with graft function. Full
      recovery after replantation, but impaired function after transplantation, was
      also reflected in the histological results: normal histological pictures of blood
      vessels, cartilage, bone and soft tissues were found in all replant recipients,
      but infiltrative vasculopathy indicating chronic rejection was found in the
      transplanted joints. The results of this animal study confirm that the procedure
      can lead to satisfactory functional results but also emphasize the need for
      perfect control of immunosuppression.

PMID- 10968533
TI  - Outcome analysis following open rotator cuff repair. Early effectiveness
      validated using four different shoulder assessment scales.
AB  - Evaluation of upper extremity function after reconstructive surgery is
      increasingly important both to predict outcome and for the control of cost
      effectiveness. Three validated, self-administered shoulder questionnaires were
      applied prospectively in 23 otherwise healthy patients with rotator cuff
      deficiency and correlated to the Constant-Murley Shoulder Score and a visual
      analogue scale for satisfaction. Seven women and 16 men with combined tears of
      supraspinatus and infraspinatus (mean age 55.3 +/- 10.5 years, r/l: 14/9, follow
      up 57.8 +/- 15.7 weeks) were gathered prospectively and evaluated pre- and
      postoperatively with the American Shoulder and Elbow Surgeons (ASES) Shoulder
      Index, the Simple Shoulder Test (SST) and the Disabilities of the Arm, Shoulder
      and Hand Module (DASH questionnaire). Additionally, a visual analogue scale for
      satisfaction was employed. All four scores and the visual analogue scale revealed
      improvement at a statistically significant level (P < 0.01) after surgery. All
      questionnaires showed a significant correlation with the Constant-Murley Shoulder
      Score (ASES: r = 0.871, P < 0.01; DASH: r = -0.758, P < 0.01, SST: r = 0.494, P <
      0.05, Pearson's correlation coefficient). Taken together, all questionnaires were
      easy to apply, and reliable evaluation of shoulder function was possible with
      significant correlation to the Constant-Murley Shoulder Score postoperatively.
      The SST was easy to apply, and compound outcome analysis was possible with the
      ASES Shoulder Index and DASH questionnaire. The DASH scale was the most complex
      evaluation instrument. The Constant-Murley Shoulder Score comprises a physical
      examination, which is advantageous but restricts the application to the office.
      For postoperative assessment without the patient having to return to the clinic,
      the ASES Shoulder Index is preferred because of its good correlation to the
      Constant-Murley Shoulder Score (r = 0.871) and the visual analogue scale for
      satisfaction (r = 0.762).

PMID- 10968534
TI  - Transtrochanteric rotational osteotomy for osteonecrosis of the femoral head with
      preoperative superselective angiography.
AB  - A prospective radiologic and scintigraphic study was made of 15 joints in 12
      patients who underwent transtrochanteric rotational osteotomy of the femoral head
      after identifying by preoperative superselective angiography which arteries
      should be preserved during surgery. The preoperative superselective angiography
      revealed that the blood supply to the femoral head was provided by the medial
      femoral circumflex artery in 12 joints and a branch of the internal iliac artery
      in 3 joints. These nutrient arteries were preserved during surgery. At the follow
      up examination made after at least 2 years, there were no cases of collapse of
      the new femoral head weight-bearing site, and also there were no cases with a
      large cold area in the femoral head on the scintigram obtained 2 months
      postoperatively. For this operative procedure, the nutrient arteries of the
      femoral head should be confirmed by preoperative superselective angiography, and
      it is essential that these arteries be preserved during surgery.

PMID- 10968535
TI  - Cervical spine stenosis due to ossification of the posterior longitudinal
      ligament in Italian patients: surgical treatment and outcome.
AB  - Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine
      is a frequent pathological entity in people of Japanese and Asian extraction and
      is reported with increasing frequency also in the USA; on the contrary, reports
      in the European and particularly in the Italian literature remain rare. This
      paper describes 8 Italian patients with cervical spine stenosis due to OPLL
      extending three to five vertebral segments (and above C3 in four cases). Magnetic
      resonance imaging shows the extent of the ossification well in terms of height
      and cord compression, while computed tomography is useful to measure the
      thickness of the bone mass and the residual spinal canal. Anterior cervical
      decompression by discectomy, corpectomy, and removal of the ossified ligament is
      the treatment of choice and results in clinical improvement in most cases.
      Decompressive laminectomy may be reserved for patients with ossification
      extending to four or five levels and above C3. The surgical technique and
      intraoperative findings are discussed.

PMID- 10968536
TI  - Bigger size and defatting of bone chips will increase cup stability.
AB  - Morcellised bone allograft in an in vitro model was used to test the tendency
      towards cup rotation using small or larger fragment sizes of an impacted graft
      bed and different fat contents. A cup cemented on an impacted graft bed of larger
      sized bone chips from the Howex bone mill containing natural marrow fat was
      loaded eccentrically until the cup rotated. This required 3450 N. The same chips
      impacted in the same way, but defatted with warm saline solution required 7000 N
      for rotation. The smaller sized bone chips from the Tracer bone mill defatted in
      a similar manner required only 1950 N for cup rotation. The conclusion was that
      larger sized chips, partly defatted, prevent rotation of a cup cemented on a
      graft bed.

PMID- 10968537
TI  - Conservative and operative treatment in cervical burst fractures.
AB  - The aim of this study is to compare the results of non-operative and anterior
      operative treatment of cervical burst and flexion teardrop fractures. Sixty-nine
      consecutive patients treated during 1980 to 1995 were reviewed retrospectively.
      Thirty-four of them had been treated with skull traction or halo-vest and 35 with
      anterior decompression, bone grafting and fixation by an anterior Caspar plate.
      Neurological functioning on admission and at the end of the follow-up was
      assessed by using Frankel's classification. Kyphosis and spinal canal
      encroachment by retropulsed fragments were measured radiographically. Operatively
      treated patients recovered more often with at least one Frankel grade (P = 0.027)
      and presented less narrowing of the spinal canal (P = 0.0006) and kyphotic
      deformity (P = 0.00003) at the end of the followup. In comparison with the
      conservative methods, the operative Caspar technique provided superior
      decompression and fixation as well as promoted the healing of cord injuries
      caused by burst and flexion teardrop fractures.

PMID- 10968538
TI  - Osseous overgrowth after post-traumatic amputation of the lower extremity in
      childhood.
AB  - Severe accidents in children may cause extreme destruction of the lower
      extremities. In some cases, there is no possibility to preserve the limbs.
      Initially, a weight-bearing stump cannot be achieved after amputation due to
      unstable local and soft tissue conditions. This critical situation is often
      complicated by one of the leading problems in the limb-deficient child - the
      development of osseous overgrowth. Bizarre overgrowth of the stump may lead to
      skin perforation, pressure ulcers, and difficulties with the prosthesis. Since
      1993, we have been able to follow five pediatric and adolescent patients (2 years
      to 17 years old) with six post-traumatic amputations of the lower extremities.
      Four of these cases developed osseous overgrowth. One child treated with initial
      autologous stump-capping had excellent soft tissue conditions and no problems
      with the artificial limb. We also report on a case of bizarre and extensive new
      bone formation. We conclude that close follow-up visits after post-traumatic
      amputations in children are essential because of new bone formation which may
      endanger the soft tissue situation of the stump. Unfortunately, surgical
      revisions have to be performed quite often. To avoid several surgical
      corrections, an initial stump-capping with autologous material from the injured
      limb can be performed. Thus, the number of secondary procedures may be reduced
      drastically.

PMID- 10968539
TI  - Development of a solitary bone cyst--a report of a case suggesting its
      pathogenesis.
AB  - The origin and natural course of solitary bone cysts (SBC) still remain
      controversial. Knowledge of the process of cyst formation and enlargement would
      be helpful for investigating its pathogenesis. Only two papers have described a
      radiodense nidus of the diaphysis as a precursor. Their cases were unique in that
      the initial lesions were in the diaphysis and that the cysts did not abut onto
      the epiphyseal line. This study reports a case in a patient with a tiny erosive
      lesion in the endosteal surface of the humeral metaphysis, which developed
      expansively into a typical large cyst over 6 years. Serial roentgenograms taken
      every year demonstrated the process of cyst enlargement. This is the first
      longitudinal study of a case with SBC documented from its onset.

PMID- 10968540
TI  - Autogenous bone marrow graft to non-ossifying fibroma with a pathologic fracture.
AB  - Non-ossifying fibroma with a pathological fracture of the radius in a 10-year-old
      girl was successfully treated by curettage and autogenous bone marrow graft. The
      lesion was completely replaced by normal bone at 1 year after the operation.
      Autogenous bone-marrow graft was considered to be a useful method for the
      treatment of non-ossifying fibroma with minimal morbidity of the graft-harvesting
      site.

PMID- 10968541
TI  - Monostotic fibrous dysplasia of the spine: report of a case involving the lumbar
      transverse process and review of the literature.
AB  - Monostotic fibrous dysplasia of the spine is rare. We report its clinical,
      radiologic and histologic features affecting a 47-year-old housewife. She
      presented with low-back pain of 1-year's duration, and radiographs showed a
      diffuse expansile lesion in the left transverse process of the fourth lumbar
      vertebra. The lesion was excised and histologically confirmed to be fibrous
      dysplasia. The patient remained well 8 years after operation. Including the
      present case, a total of 22 cases of monostotic fibrous dysplasia of the spine
      were found in the literature. Combining these reported cases, we found that the
      condition affects either sex with equal frequency and presents at any age, the
      mean being 32 years. There is no predilection for any part of the spinal column,
      though sacral or coccygeal involvement is distinctly rare. It most commonly
      involves the body and adjacent pedicle, although no part of the vertebra is
      spared. It is worth noting that a propensity for progressive enlargement, even to
      the extent of causing graft destruction, exists if the lesion is left untreated
      or incompletely treated. Complete removal of all involved bone, together with
      stabilization, should therefore be the treatment of choice for this condition.

PMID- 10968542
TI  - Reflex sympathetic dystrophy in children.
AB  - This report presents the case of an 8-year-old boy who underwent a second
      clubfoot operation following early-stage reflex sympathetic dystrophy (RSD).
      After other conditions had been ruled out, the patient was submitted to
      physiotherapy supported by antiphlogistic and analgesic drugs as well as a
      partial immobilisation of the affected extremity. He remained asymptomatic during
      the following 4 weeks. RSD in children is not a well-recognised entity. This case
      of early-stage RSD illustrates the need to be aware of this possible
      complications after operation in the differential diagnosis of local pain and
      swelling of a limb.

PMID- 10968543
TI  - Giant schwannoma of the back.
AB  - We treated a patient with giant schwannoma of the back. The tumor measured 35 x
      25 x 12 cm and weighted 1840 g. Histological diagnosis was benign schwannoma. To
      our knowledge, there is no previous report of such a large schwannoma of the
      back.

PMID- 10968544
TI  - Failure of osteosynthesis and prosthetic joint infection due to Mycobacterium
      tuberculosis following a subtrochanteric fracture: a case report and review of
      the literature.
AB  - We report a patient with a subtrochanteric fracture, for whom internal fixation
      failed and a prosthetic joint replacement was complicated by a local reactivation
      of a Mycobacterium tuberculosis infection. After hip replacement with revision
      and adequate medical therapy, a full recovery was attained without the necessity
      of removing the artificial joint.

PMID- 10968545
TI  - Expression of keratan sulfate at the arthroplasty surface after cup arthroplasty.
AB  - Fibrous tissue which regenerated on the acetabular arthroplasty surface was
      obtained from a 52-year-old woman who underwent total hip replacement after cup
      arthroplasty. The histological features of this newly formed fibrous tissue and
      expression of keratan sulfate, which is a characteristic matrix component of
      articular cartilage, were studied. Microscopic observation revealed that the
      arthroplasty surface consisted mainly of fibrous tissue which did not show
      metachromasia with toluidine blue staining, but there were many nodular
      structures communicating with the bone marrow. Immunostaining for keratan sulfate
      revealed clear positive staining around the cells of the nodular structures
      communicating with the bone marrow, while only weakly positive staining was
      observed in the superficial layer of the loose fibrous tissue. The present study
      revealed marked formation of articular cartilaginous tissue in areas having good
      communication with the bone marrow, which indicates that maintenance of this
      communication may be necessary to improve the outcome of cup arthroplasty.

PMID- 10968546
TI  - Pseudotumor occurring in hemophilia.
AB  - A patient suffering from severe hemophilia combined with a large pseudotumor of
      his left thigh is presented, and the case history discussed. The occurrence of
      this tumor in hemophilia is considered with respect to the clinical,
      radiological, and laboratory findings.

PMID- 10968547
TI  - Traumatic abscess of pectoralis major.
AB  - Pectoralis major rupture is a well-recognised but uncommon injury that rarely
      leads to complications. We present an unusual case where the resultant haematoma
      following a partial rupture became infected and caused problems with diagnosis.
      We are only aware of one previous report of this.

PMID- 10968548
TI  - Surgical management of tophaceous gout in the hand.
AB  - A patient who suffered from severe deforming arthritis secondary to chronic
      tophaceous gout with multilobular, solid, tender, enlarged subcutaneous nodules
      and draining tophi in both hands was evaluated and treated by second ray
      amputation of the most deformed second finger to provide a more functional
      result.

PMID- 10968550
TI  - Periprosthetic bone remodelling after total knee arthroplasty: early assessment
      by dual energy X-ray absorptiometry.

PMID- 10968549
TI  - A rare case of osteoporotic spine fracture associated with epidural lipomatosis
      causing paraplegia following long-term cortisone therapy.
AB  - Cushing's syndrome is frequently associated with osteoporosis. Therefore, the
      incidence of osteoporotic spine fractures is significant. They are a rare cause
      of paraplegic syndromes. Additionally, epidural lipomatosis may occur in those
      patients. The combination of both fracture and lipomatosis may cause neurological
      deficit. A case of a young patient suffering from drug-induced Cushing's syndrome
      is reported. She developed progressive paraplegia. Radiographs demonstrated
      kyphosis of the thoracic spine from T7 to T9 and pathologic fractures. Urgent
      operation was planned to stabilize and decompress the spinal cord in the area of
      the kyphosis. Fortunately, magnetic resonance imaging (MRI) was conducted first.
      It confirmed pathologic fractures of T7-9 but also showed massive epidural fat
      extending from the level of T1 to T9. As suspected, laminectomy alone in the area
      of the fracture proved to be insufficient, as shown by myelography during
      operation. For treatment of paraplegia in this case of symptomatic epidural
      lipomatosis, an expanded laminectomy was necessary to remove all the epidural
      fat. Having undergone this procedure, the patient is now recovering from
      paraplegia. Our experience suggests that care should be taken before operative
      treatment of patients with pathological fractures in combination with Cushing's
      syndrome. In addition to vertebral fractures, epidural lipomatosis has to be
      taken into consideration. Those patients with neurological deficits have to be
      treated by an extensive laminectomy.

PMID- 10968551
TI  - Electromagnetic fields: low dose exposure, current update.
AB  - OBJECTIVES: The controversial discussion of low-dose electromagnetic field (EMF)
      effects on human health derives from a lack of knowledge of the mechanism of
      action and proven results of cellular, animal and human experiments. The paper
      gives an overview of the current results of scientific research. METHODS: Review
      based on the legal measurements of the EU parliament, the ICNIRP guidelines, the
      current literature and personal contacts with scientist in the field. RESULTS:
      Epidemiologic research shows a low degree of association, inconsistency and
      missing dose-effect relations. A biologic mechanism of action is still debatable.
      When observing ICNIRP guideline values, no harm to human health has been shown;
      but the statement, "EMF are not harmful", cannot be made. Implanted electric
      devices, like pace-makers, are more sensitive to EMF and need special attention.
      CONCLUSION: There is no scientific basis as to the harmful effects of EMFs on
      human health, when ICNIRP guidelines are observed. Hypersensitivity to EMF has
      not been clinically proved.

PMID- 10968552
TI  - Occupational standards for the protection of employees in biotechnology.
AB  - A growing number of employees are exposed to biological agents (BAs) at the
      workplace. Their handling can be associated with the risk of occupational
      illnesses like infections, allergic or toxic reactions. Several legal
      considerations are making requirements for the safe handling of BAs necessary. A
      specific risk assessment has to consider both the adverse health effects deriving
      from BAs and the exposure situation at the workplace. Industrial hygiene is of
      critical importance for safe handling, especially with regard to allergic
      reactions. Occupational surveillance programs can help to further minimize the
      risks, especially in preventing infections through vaccinations and in counseling
      persons with impaired immune systems. For accidental exposures medical emergency
      plans should be prepared. Occupational medical examination programs, vaccinations
      and counseling of employees must be adapted to the outcome of the risk
      assessment.

PMID- 10968553
TI  - Health, safety and environmental protection in a biological research laboratory.
AB  - This manuscript summarizes the mandatory regulations for Health, safety and
      environmental protection (HSE) at the Novartis Forschungsinstitut-Vienna to
      ensure the safe and contained biological laboratory work especially with class II
      agents in the specialized biosafety level 2 (BL2) facilities available at this
      institute. These regulations apply to work practices conducted within these
      facilities; to special safe-containment features of these BL2 facilities; to
      containment and decontamination of biohazardous or potentially biohazardous
      materials of risk class II; and to the procedures in place to guarantee that
      these regulations are strictly carried out, and that only individuals with the
      appropriate training and approval have access to these facilities. The
      regulations governing BL2 facilities summarized here have been taken directly
      from CDC and NIH public documents; any special adaptations or additions to these
      regulations have been stated as such, in order to make these guidelines as
      transparent and nonredundant as possible.

PMID- 10968554
TI  - Safety evaluation of genetically modified foods.
AB  - The concept of substantial equivalence has been accepted as the cornerstone of
      the health hazard assessment of genetically modified (GM) foods (OECD 1993).
      Substantial equivalence is the most practical approach to address the safety of
      foods or food components derived from GM crops and is based on comparison of the
      phenotypic and compositional characteristics of the parent crop and the GM crop.
      Basically, three categories of GM crops can be considered (FAO/WHO 1996; EU
      1997): (a) GM crops which have the same composition as the parent crop, (b) GM
      crops which have the same composition as the parent crop with the exception of a
      well-defined trait, and (c) GM crops which are different from the parent crop.
      For the safety assessment of the first category of GM foods only a molecular
      characterisation of the genetic insert is sufficient, whereas for the second
      category a safety assessment of the expressed protein(s) is also required. For
      the last category an extensive evaluation including bioavailability and
      wholesomeness studies are required, beside the molecular characterisation and
      safety assessment of the expressed protein(s) and their products. By molecular
      characterisation is meant the position, nature, stability and number of copies of
      the inserted DNA. Substantial equivalence is established by the determination of
      the phenotypic characteristics (e.g. resistance against diseases, agronomic
      properties) and the complete chemical composition of the plant including
      nutrients, toxicants, antinutrients, and allergens. The toxicity of the expressed
      protein(s) is assessed by their homology with known protein toxins, degradation
      in the gastro-intestinal tract, stability to food processing and acute toxicity
      in rodents. The possible allergenicity of the expressed proteins is evaluated by
      comparison of their amino acid sequence with that of known allergens and
      determination of their stability to digestion and food processing. If the source
      of the genetic insert is allergenic then the use of solid-state immunoassays,
      skin prick tests and even food challenge tests can be considered.

PMID- 10968555
TI  - Are natural gene sequences patentable?
AB  - The title question is answered in the affirmative. The patentability of natural
      gene sequences is based on general principles of patent law, and depends on
      novelty, inventive steps and industrial applicability of the subject matter to be
      patented. Patentability is further confirmed by the particular articles of the
      European Patent Convention and the recent EC Directive on the legal protection of
      biotechnological inventions.

PMID- 10968556
TI  - Recombinant DNA technology: chances, risks, ethical considerations.
AB  - In recent years, undesirable costs and the likely payoffs of DNA technology have
      been widely discussed. In this paper, the author concentrates on molecular
      genetic diagnostics. One of the main benefits of molecular genetic diagnostics is
      its predictive potential. However, the predictive dimension inherent in this type
      of diagnostics also gives rise to a host of problems.

PMID- 10968557
TI  - Psychosocial factors in the work environment--a new challenge for occupational
      health physicians in the chemical industry: introduction.

PMID- 10968558
TI  - Workplace and workforce 2000+ -the future of our work environment.
AB  - OBJECTIVES: Research in the Human Resource Department at the University of
      Mannheim is directed towards the exploration of future work structures and
      design, and their effects on employees and employment relations. METHODS: The
      main methods applied are trend extrapolation and simulation in combination with
      delphi research methodology. The trends observed during the last decade suggest
      that the workplace and workforce in the new millenium will primarily be affected
      by flexibilization, decentralization, and globalization. RESULTS AND CONCLUSIONS:
      Flexibilization will lead to a core group with unlimited full employment and an
      increasing larger group of short-term limited and/or part-time employees who face
      severe employment risks, ultimately resulting in stress. Flexibilization will
      also affect the workplace. Information technologies will dissolve social
      entities. The virtual company suppresses social interaction and will as a
      consequence create new forms of alienation. Decentralization will increase the
      responsibility for business processes. Employees will be regarded as business
      process owners and will be held responsible for their results, a situation which
      again creates new stress factors. Globalization enhances competition, which in
      turn will encourage competitive attitudes at the workplace. Internal market
      mechanisms will take the place of performance appraisals by management. Market
      evaluation will substitute leadership styles and communication, which stand for
      the human side of enterprise. The psychosocial problems arising from these
      developments will produce new challenges for occupational health professionals.

PMID- 10968559
TI  - Psychosocial and clinical risk factor profiles in managers.
AB  - OBJECTIVES: Over the past 10 years the IAS Foundation has performed more than
      15,000 PREVENT check-ups on managers. In addition to a comprehensive clinical
      program of preventive examinations, the main emphasis is placed on extensive
      counseling. This counseling centres not only on personal behaviour patterns
      affecting the individual's health, but also on the psychomental capabilities of
      the patient within the context of the psychosocial stresses in managerial
      positions. METHODS: Three cross-sectional studies examined: (1) the major
      cardiovascular risk factors (n = 974), (2) the psychosocial structure (n = 2,800)
      and (3) the relationships between clinical risk factors and psychological
      structural features (n = 200). RESULTS: According to expectations, managers
      showed somewhat lower cardiovascular risk levels than did other professional
      groups. However, nearly 70% of them reported various unspecific, psychovegetative
      complaints. Managers were subdivided into four psychological types, each
      representing roughly one quarter of the series: Type 1: anxiety, tension (20.5%);
      Type 2: repression, lack of self-control (22.2%); Type 3: challenge, ambition,
      self-control (27.6%); Type 4: healthy living, with self-control (29.7%). Type 3
      resembles most closely classic type A behaviour and is seen in a good quarter of
      the overall cohort. This may indicate that not only people showing type A
      behaviour are predestined to occupy managerial positions, but that people with a
      type B structure also take up managerial positions. It is, however, in particular
      the type B behavioural patterns that are also associated with increased
      psychovegetative complaints. The relationships between psychosocial structural
      variables and clinical risk factors such as hypercholesteremia and high blood
      pressure are not very strong. CONCLUSIONS: Occupational health measures in
      organisations should also be established for managers, as they present an
      important employee group within the enterprise. In addition to examining them for
      cardiovascular risks, counseling and coaching programmes on preventive measures
      and recommended behaviour at work should be a primary concern.

PMID- 10968560
TI  - Psychosocial work environment and the risk of coronary heart disease.
AB  - OBJECTIVES: Remarkable changes in the working situation have led to the
      increasing importance of psychomentally and socio-emotionally demanding
      conditions at work. With the help of theoretical models, those highly prevalent
      psychosocial work environments were conceptualized which influence the risk of
      coronary heart disease by enhanced activation of the autonomic nervous system.
      One of the most prominent theoretical approaches, the job strain model, and a
      more recent approach, the effort-reward imbalance model, are discussed in the
      paper. EMPIRICAL EVIDENCE: Findings from prospective and cross-sectional studies
      indicate that job strain and effort-reward imbalance at work define specific
      conditions of chronic work stress that are associated with an elevated risk of
      coronary heart disease (CHD). Respective multivariate odds-ratios range from 1.2
      to 5.0 with respect to job strain, and from 1.5 to 6.1 with respect to effort
      reward imbalance. These associations are explained neither by established
      behavioral or biomedical risk factors nor by physical and chemical hazards at
      work, rather they define independent, new work-related risk conditions. There is
      additional evidence that effort-reward imbalance may mediate the association of
      some traditional occupational exposures, such as shift work, with cardiovascular
      risk: in a cross-sectional study, prevalence odds ratios of hypertension and
      atherogenic lipids attributable to effort-reward imbalance were relatively
      highest among shiftworkers as compared to daytime workers. Preliminary results
      from intervention programs based on the theoretical models document favorable
      effects on health. CONCLUSIONS: Information derived from theoretical models on
      psychosocial work environment may help to better identify populations at risk and
      to develop and apply specific, theory-guided preventive activities in the future.

PMID- 10968561
TI  - Objectifying psychomental stress in the workplace--an example.
AB  - BACKGROUND: Psychomental stress is a major source of illness and reduced
      productivity. Data objectifying physiological stress responses are scarce. We
      studied salivary cortisol levels in a highly stressful environment, the pediatric
      critical care unit. The aim was to identify targets for organizational changes,
      to implement these changes and to assess their impact on cortisol levels. DESIGN:
      Repeated measurements observational cohort study (before and after intervention).
      SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed
      pediatric intensive care unit. Between study periods team A experienced a major
      exchange of experienced staff while the turnover rate in team B remained average.
      MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2
      h and after stressful events. Nurses in study period I showed elevated cortisol
      levels at the beginning of the late shift, interpreted as an anticipatory stress
      reaction. To ease conditions during the early part of the late shift (conflicting
      tasks, noise and crowding), we postponed the afternoon ward round, limited non
      urgent procedures and introduced a change in visiting hours. The early shift,
      which was not affected by the intervention, served as control. MAIN RESULTS: Both
      crude and adjusted analysis revealed a decrease of cortisol levels at the
      beginning of the late shift in team B (p = 0.0009), but not in team A (p =
      0.464). The control situation showed no difference between teams and study
      periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team
      following organizational changes, which was probably overridden by the disruption
      of social coherence in the second team.

PMID- 10968562
TI  - Asbestos as reference material for fibre-induced cancer.
AB  - The objective of this paper is to review published data on the carcinogenicity of
      asbestos fibres with regard to the elucidation of a potential risk originating
      from exposure to man-made vitreous fibres (MMVF). Steps in the comparison of the
      two fibre classes are characterization of the fibres, pulmonary deposition,
      biodurability and biopersistence and a review of the cancer risk from asbestos
      fibres after inhalation in rats and humans. Various dust samples of chrysotile,
      crocidolite, and amosite were used as reference materials in studies with
      experimental animals. These fibres are normally thinner and shorter than MMVF.
      These differences in dimensions cause differences in the deposition in the
      airways. In addition, significant dissimilarities exist in the deposition pattern
      between rats and humans. Data from biopersistence studies show that focusing only
      on fibres longer than 20 microm and using weighted half-time for a
      characterization of risk may be misleading. Inhalation experiments with rats need
      fibre exposure concentrations over 100 times higher to match the lung cancer risk
      of asbestos workers, and about 1,000 times higher to reach the same mesothelioma
      risk. Also, the striking difference between the low lung burden of amphibole
      fibres of asbestos workers with mesothelioma and the more than 1,000 times higher
      lung burden of rats with a low mesothelioma risk demonstrates the low sensitivity
      of the inhalation test model for the carcinogenic potency even of crocidolite
      fibres. It can be concluded that the rat inhalation model is also not sensitive
      enough to predict the cancer risk of other fibre types for humans.

PMID- 10968563
TI  - Determinants of the pathogenicity of man-made vitreous fibers (MMVF).
AB  - INTRODUCTION AND OBJECTIVES: A number of man-made vitreous fibers (MMVF) have
      been developed over the years to replace asbestos fibres in its uses as
      insulating material. Concerns have been raised that these man-made fibers may
      also pose a significant health hazard when inhaled during their manufacture and
      application. As will be discussed in this brief overview, dose, dimension and
      durability of fibrous particles are key parameters with respect to the induction
      of adverse pulmonary effects, including carcinogenicity as well as non-cancer
      effects. In particular, fiber biopersistence plays a most important role for
      pulmonary pathogenicities, and consequently biopersistence receives greatest
      attention in the search of new fibrous materials. METHODS AND RESULTS: Tests to
      evaluate fiber biopersistence include the administration of fibers by a short
      term inhalation (5 days) or intratracheal instillation into rats. Advantages of
      the inhalation methodology include the even distribution throughout the lung
      administered by a physiological process. A disadvantage of this method is the
      limited respirability of long fibers in the rat whereas they are well respirable
      by humans. Such long fibers ( > 20 microm) have the greatest potential for
      tumorigenicity and need special consideration in connection with the evaluation
      of fiber biopersistence. Enrichment of the inhaled aerosol by these long fibers
      needs to be considered in order to deposit enough of them in the lower
      respiratory tract of the rat. In contrast, the advantage of the instillation
      technique is that these long fibers can be delivered to the lung. However, the
      major disadvantages of intratracheal instillations are the potential of the
      administered fibers to form clumps and aggregates in the airways and the
      induction of a major inflammatory response when high-bolus doses are
      administered. This could influence fiber dissolution in the lungs significantly.
      CONCLUSIONS: At the same delivered lung dose, a fiber of low biopersistency has
      the least effect and is, therefore, less likely to induce lung or pleural tumors
      even under chronic exposure conditions. Respective animal studies with more
      fibers of different biopersistence have confirmed this general principle. It is
      very important that, when evaluating and interpreting fiber effects observed in
      experimental animals, species differences with respect to respirability, lung
      retention and mechanisms of responses are considered.

PMID- 10968564
TI  - Natural organic fibers--health effects.
AB  - OBJECTIVES: Natural organic fibers are used in large quantities in the production
      of paper products and textiles. They are also constituents of food and added to
      food to promote health. The objective of this review is to evaluate the health
      effects of natural organic fibers. The health effects of dietary fibers are
      excluded from the review. METHODS: This is a literature review. RESULTS: Exposure
      to these fibers in industry is usually not characterized as fibers but as dust.
      Rather dusty conditions have been reported in both paper and textile industries
      with concentrations up to and above 30 mg/m3. Both in the paper and textile
      industry inorganic fibers may occur making it hard to evaluate health effects of
      natural organic fibers from studies of workers in the paper and textile industry.
      There seems to be no increased risk of mesothelioma, lung cancer or lung fibrosis
      in workers exposed to natural organic fibers in contrast to workers exposed to
      inorganic crystalline fibers as asbestos. However, workers with a heavy exposure
      to paper dust or textile dust seem to have an increased risk of obstructive lung
      disease and bronchitis. These effects have not been causally linked to the
      fibrous shape of the particles but rather to the dust, chemicals absorbed on the
      dust or microorganisms occurring together with the dust. There is some indication
      that work in the textile industry may increase the risk of sinonasal cancer, but
      the etiological agents are unknown. CONCLUSION: Natural organic fibers are not
      causally linked with the well-known effects of some inorganic fibers, i.e.
      mesothelioma, lung cancer, lung fibrosis or some pleural diseases. The health
      effects of natural organic fibers, e.g. irritative effects, seem not to be linked
      to their fibrous shape.

PMID- 10968565
TI  - Biodegradability of inhaled p-aramid respirable fibre-shaped particulates:
      representative of other synthetic organic fibre-types?
AB  - OBJECTIVES: Biopersistence, or alternatively, biodegradability (i.e., low
      biopersistence) represents an important concept in fibre toxicology. The studies
      described below were undertaken to investigate the mechanisms through which
      inhaled para-aramid (p-aramid) respirable, fibre-shaped particulates (RFP) are
      biodegraded in the lungs of exposed rats and hamsters; in contrast, cellulose
      fibres, another organic fibre-type, are known to be biopersistent. To investigate
      the mechanisms of RFP biodegradation, we have hypothesized that lung fluids
      activate p-aramid RFP following deposition, and the RFP are then vulnerable to
      enzymatic attack in the lungs. METHODS: To test the hypothesis, p-aramid RFP or
      cellulose RFP were instilled into the lungs of rats and the lungs digested 24 h
      post-exposure using two different digestion techniques: (1) a conventional
      ethanolic KOH method, and (2) an enzymatic method which simulates lung enzymes.
      RESULTS: The enzymatic but not the KOH method artificially cleaved the p-aramid
      RFP recovered from rat lungs. Next, p-aramid RFP or cellulose RFP were incubated
      with saline or lung fluids and then processed by one of the two digestion
      techniques. Mean lengths of p-aramid RFP processed with KOH and evaluated by SEM
      were 13.4 microm; in contrast, mean lengths of p-aramid RFP samples, incubated in
      lung fluids and treated with the enzymatic method were 8.8 microm. The enzymatic
      digestion method had no discernible effect on shortening of cellulose RFP,
      indicating that the results with p-aramid were specific. CONCLUSIONS: Our data
      indicate that components of lung fluids coat and catalyze the p-aramid, thereby
      predisposing the RFP to enzymatic cleavage. This could play a significant
      mechanistic role in facilitating the transverse cleavage or shortening of inhaled
      p-aramid RFP in the lungs of exposed rats and hamsters.

PMID- 10968566
TI  - Future structures of industrial work: management of occupational safety and
      occupational health. Position of management and labour and the accident insurance
      of the chemical industry.

PMID- 10968567
TI  - Toxicokinetics of intravenous fluoride in rats with renal damage caused by high
      dose fluoride exposure.
AB  - Fluoride (F) complexes are used in some fields of industry and medicine. F
      excretion mainly depends on kidney function. Urinary F concentration is measured
      to monitor the health of workers exposed to F. The toxicokinetics of F were
      studied by analyzing plasma concentration of F after intravenous injection of
      2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose-response relationship was
      recognized between these F doses and renal tissue injury. Blood samples were
      removed at 0, 10, 20, and 30 min, and after 1, 2, 3, 4, 5, and 6 h after
      injection. Plasma concentration-vs-time profiles were evaluated by a nonlinear
      least-squares method for fitting data to polyexponential equations and
      calculation of relevant pharmacokinetic parameters. Results indicated that a two
      compartment model could describe the elimination of F from plasma. The beta rate
      constant, total plasma clearance (C1) and first-order rate constants (K21, Kel)
      decreased, and the half-time of the beta-phase (t1/2beta) was significantly
      prolonged with increasing dose. The kidney is the main target organ for F
      toxicity. Acute exposure to high doses of F damages renal tissue and causes renal
      dysfunction. The C1 of F is mainly dependent on renal F excretion. Since severe
      kidney damage markedly affected the toxicokinetics of F and decreased its
      elimination, other nephrotoxic indicators and measurement of plasma F
      concentration are necessary for monitoring high-dose F exposure.

PMID- 10968568
TI  - Successful treatments of lung injury and skin burn due to hydrofluoric acid
      exposure.
AB  - Recent growth in the electronics and chemical industries has brought about a
      progressive increase in the use of hydrofluoric acid (HF), along with the
      concomitant risk of acute poisoning among HF workers. We report severe cases of
      inhalation exposure and skin injury which were successfully treated by
      administering a 5% calcium gluconate solution with a nebulizer and applying 2.5%
      calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for
      surface treatment after welding stainless steel, and was hospitalized with rapid
      onset of severe dyspnea. On admission to the critical care medical center he had
      widespread wheezing and crackles in his lungs. Chest radiograph showed a fine
      diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high
      concentrations of F in serum and urine were disclosed. He was immediately given
      5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB),
      utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not
      demonstrate any abnormality. He was discharged very much improved on the 22nd
      hospital day. Case 2: A 35-year old worker at an electronics factory was admitted
      to his local hospital with severe skin burn on his face and neck after exposure
      to 100% HF. Treatment began with immediate copious washing with water for 20 min.
      Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid
      measure. Persistent high concentrations of serum and urinary F were disclosed for
      2 weeks. After treatment with applications of HF burn jelly, he was confirmed as
      being completely recovered. The present cases and a review of published data
      suggest that an adequate method of emergency treatment for accidental HF
      poisoning is necessary.

PMID- 10968569
TI  - Pharmacokinetics and effects after intravenous administration of high-dose boron
      to rat.
AB  - Boron (B) compounds have been widely used in the chemical industry, agriculture,
      and environmental science. The kinetics and toxicity of B were studied by
      analyzing several serum and urine parameters after a single intravenous injection
      of sodium tetraborate solution (B: 85.7 mg/kg) in Wistar male rats. Blood samples
      were removed at 0, 1, 2, 4, and 6 h after injection. The serum parameters studied
      included: B, Na, Ca, K, P, Mg, gamma-GTP, AST, ALT, BUN, Cr, CK, LDH and ALD.
      Plasma concentration-time profiles of B were evaluated by a nonlinear least
      squares method for fitting data to polyexponential equations and calculation of
      relevant pharmacokinetic parameters. Urine samples were collected from the
      bladder following infusion. The urinary parameters that were studied included
      urine volume and excretion of B, Cr and NAG. Results indicated that a two
      compartment model could describe the elimination of B from plasma after
      intravenous administration. Urine volume significantly increased. A diuretic
      effect of B was noted.

PMID- 10968570
TI  - Public health in the new millennium I: Technology.

PMID- 10968571
TI  - Is RJR still going after the "kiddie" market?

PMID- 10968572
TI  - Defining infertility.

PMID- 10968573
TI  - Not-so-sweet charity.

PMID- 10968574
TI  - WHO and UN: AIDS not losing momentum. World Health Organization. United Nations.

PMID- 10968575
TI  - WHO's new mental health strategies. World Health Organization.

PMID- 10968576
TI  - Death rates of "atomic vets".

PMID- 10968577
TI  - New cancer mortality atlas.

PMID- 10968578
TI  - Reducing medical errors requires system changes.

PMID- 10968579
TI  - New health care quality data bank.

PMID- 10968580
TI  - "Club drugs" take center stage.

PMID- 10968581
TI  - Halting the obesity epidemic: a public health policy approach.
AB  - Traditional ways of preventing and treating overweight and obesity have almost
      invariably focused on changing the behavior of individuals, an approach that has
      proven woefully inadequate, as indicated by the rising rates of both conditions.
      Considering the many aspects of American culture that promote obesity, from the
      proliferation of fast-food outlets to almost universal reliance on automobiles,
      reversing current trends will require a multifaceted public health policy
      approach as well as considerable funding. National leadership is needed to ensure
      the participation of health officials and researchers, educators and legislators,
      transportation experts and urban planners, and businesses and nonprofit groups in
      formulating a public health campaign with a better chance of success. The authors
      outline a broad range of policy recommendations and suggest that an obesity
      prevention campaign might be funded, in part, with revenues from small taxes on
      selected products that provide "empty" calories-such as soft drinks-or that
      reduce physical activity-such as automobiles.

PMID- 10968582
TI  - Culturally competent health care.

PMID- 10968583
TI  - The voices of children: a violence prevention project.

PMID- 10968585
TI  - Incidence of severe unintentional carbon monoxide poisoning differs across
      racial/ethnic categories.
AB  - OBJECTIVE: This study was conducted to test the hypothesis that the incidence of
      severe, acute, unintentional carbon monoxide (CO) poisoning differs across
      racial/ethnic categories. METHODS: The authors retrospectively reviewed medical
      records of all Washington State residents treated with hyperbaric oxygen for
      severe, acute, unintentional CO poisoning from December 1, 1987, through February
      28, 1997. RESULTS: Among 586 Washington State residents treated with hyperbaric
      oxygen for severe, acute, unintentional CO poisoning, racial/ethnic designations
      could be determined from record review for 530 (90%). The black and Hispanic
      white populations of Washington State had higher relative risks for severe,
      acute, unintentional CO poisoning than the non-Hispanic white population. The
      most common sources of CO poisoning differed by racial/ethnic category.
      CONCLUSIONS: Members of certain groups in Washington State are at higher risk for
      severe, unintentional CO poisoning. Public education programs regarding CO
      exposure should be targeted to populations at risk.

PMID- 10968584
TI  - Disclosure of HIV status to medical providers: differences by gender, "race," and
      immune function.
AB  - OBJECTIVE: The authors used data from a larger study to explore differences by
      gender, self-reported racial identification, and immune function in disclosure of
      HIV-positive serostatus to medical providers (dentists, family doctors, and
      emergency room [ER] and obstetrics-gynecology [ob/gyn] providers). METHOD: The
      authors analyzed interview responses from a convenience sample of African
      American and white men and women receiving HIV medical care at urban hospitals
      and clinics in St. Louis. Missouri. RESULTS: Of 179 respondents using at least
      one of three types of providers, 124 (69%) disclosed their HIV status to all
      applicable types of providers, 39 (22%) disclosed to only one or two types of
      providers, and 16 (9%) did not disclose to any of these types of providers.
      "Race" and CD4 count, but not gender, were independently associated with
      disclosure to dentists, family doctors, and ER providers in multivariate logistic
      regression analyses. CONCLUSIONS: Differences in disclosure rates, especially
      among patients who may be asymptomatic, suggest a need for public health
      education of both medical providers and patients with HIV.

PMID- 10968586
TI  - Disparities in premature coronary heart disease mortality by region and
      urbanicity among black and white adults ages 35-64, 1985-1995.
AB  - OBJECTIVES: Regional and urban-rural disparities in premature coronary heart
      disease (CHD) mortality were evident in the US as early as 1950. Recent favorable
      trends at the national level may obscure less favorable outcomes for certain
      regions and localities. The authors examined trends in premature CHD mortality
      for 1985-1995 for black and white adults ages 35-64 years for four categories of
      urbanicity in two regions of the US (South and non-South). METHODS: All counties
      in the US (excluding Alaskan counties) were grouped by urbanicity and region.
      Annual age-adjusted CHD mortality rates were calculated for adults ages 35-64 by
      racial category (African American or white) and gender for each geographic area
      for the years 1985- 1995. Loglinear regression models were used to estimate
      average annual percent declines in mortality for each of 28 geo-demographic
      groups. Data were also collected on selected socioeconomic resources by
      urbanicity for the non-South (excluding Alaska) and South. RESULTS: For both
      white and black adults ages 35-64, the highest rates of premature CHD mortality
      and slowest mortality declines were observed in the rural South. For white men
      and women, marked disparities in premature CHD mortality across categories of
      urbanicity were noted in the South but not outside the South. Unexpectedly high
      rates of premature CHD mortality were observed for African Americans in major
      metropolitan areas outside the South despite favorable levels of socioeconomic
      resources. CONCLUSIONS: Disparities in premature CHD mortality by region and
      urbanicity appear to have widened between 1985 and 1995. Residents of the rural
      South had the highest rates of premature CHD mortality, and rural communities in
      the South face significant barriers to effective heart disease prevention and
      control.

PMID- 10968587
TI  - National Immunization Survey: the methodology of a vaccination surveillance
      system.
AB  - The National Immunization Survey (NIS) was designed to measure vaccination
      coverage estimates for the US, the 50 states, and selected urban areas for
      children ages 19-35 months. The NIS includes a random-digit-dialed telephone
      survey and a provider record check study. Data are weighted to account for the
      sample design and to reduce nonresponse and non-coverage biases in order to
      improve vaccination coverage estimates. Adjustments are made for biases resulting
      from nonresponse and nontelephone households, and estimation procedures are used
      to reduce measurement bias. The NIS coverage estimates represent all US children,
      not just children living in households with telephones. NIS estimates are highly
      comparable to vaccination estimates derived from the National Health Interview
      Survey. The NIS allows comparisons between states and urban areas over time and
      is used to evaluate current and new vaccination strategies.

PMID- 10968588
TI  - Diethylene glycol deaths in Haiti.

PMID- 10968589
TI  - Executive summary: a report of the Surgeon General on mental health.

PMID- 10968590
TI  - The North Carolina Institute for Public Health: science into service.

PMID- 10968591
TI  - Images in infectious diseases in obstetrics and gynecology. Endometrial
      tuberculosis.

PMID- 10968592
TI  - Semiquantitative bacterial observations with group B streptococcal
      vulvovaginitis.

PMID- 10968593
TI  - Immunotherapy of gynaecological high-risk human papilloma virus infection with
      human leukocyte ultrafiltrate.
AB  - OBJECTIVE: In this preliminary presentation the outcome of women following
      systemic treatment of cervical human papilloma virus (HPV) with a leukocyte
      ultrafiltrate is reported. METHODS: Cervical brush specimens of 819 women with
      low-grade CIN-1 were evaluated for HPV infection. HPV-positive patients were
      treated either by cone biopsy because of suspicious colposcopy or by antibiotics
      for symptoms of bacterial cervicitis. The remaining women were considered as
      asymptomatic carriers of HPV and underwent systemic therapy by a human leukocyte
      ultrafiltrate in a dosage of 5 IE, 6 times in the first 2 weeks, and additionally
      as a single dose at weeks 4, 6, 8 and 10. RESULTS: The leukocyte ultrafiltrate
      was administered to 97 HPV-positive women. In follow-up 88.7% were HPV negative
      at week 6; the remaining 11 women were tested negative after completion of a
      second course of therapy. CONCLUSIONS: These preliminary data on the successful
      treatment of HPV infection by a leukocyte ultrafiltrate are very promising but
      have to be supported by additional research.

PMID- 10968595
TI  - Is antenatal group B streptococcal carriage a predictor of adverse obstetric
      outcome?
AB  - OBJECTIVES: While early-onset neonatal GBS sepsis is positively associated with
      premature birth and prolonged rupture of membranes, there is debate in the
      literature as to whether maternal GBS colonization is a predictor of adverse
      obstetric outcome. This is a critical issue to resolve for appropriate management
      (expectant vs. interventional management) of the patient presenting with
      premature rupture of membranes, who has no overt signs of sepsis, but who is
      colonized with GBS. METHODS: Since 1981 it has been hospital policy to screen all
      public patients antenatally for genital carriage of GBS by collection of a low
      vaginal swab at 28-32 weeks. All patients colonized with GBS antenatally are
      given penicillin as intrapartum chemoprophylaxis. Review of all GBS-colonized
      antenatal patients for a 12-month period (580 of 4,495 patients) and a randomized
      (every fourth consecutive antenatal patient) number of noncolonized patients
      (958) was made. Lower vaginal GBS colonization and other risk factors for preterm
      delivery were assessed using univariate and multivariate generalized linear
      modeling. RESULTS: In the study group, the maternal GBS colonization rate was
      12.9%. When cofounding variables were controlled in a multivariate analysis, the
      association between antepartum GBS colonization and preterm labor and preterm
      rupture of membranes was not significant. CONCLUSION: Maternal antenatal carriage
      of GBS does not predict preterm labor. Therefore it is appropriate that expectant
      management occur for a GBS-colonized woman who ruptures her membranes, is not in
      labor, and has no evidence of sepsis.

PMID- 10968594
TI  - Antifungal activity of local anesthetics against Candida species.
AB  - OBJECTIVE: To evaluate the activity of benzydamine, lidocaine, and bupivacaine,
      three drugs with local anesthetic activity, against Candida albicans and non
      albicans strains and to clarify their mechanism of activity. METHODS: The minimal
      inhibitory concentration (MIC) was determined for 20 Candida strains (18 clinical
      isolates and two American Type Culture Collection strains). The fungistatic
      activity was studied with the fluorescent probe FUN-1 and observation under
      epifluorescence microscopy and flow cytometry. The fungicidal activity of the
      three drugs was assayed by viability counts. Membrane alterations induced in the
      yeast cells were evaluated by staining with propidium iodide, by quantitation of
      intracellular K+ leakage and by transmission electron microscopy of intact yeast
      cells and prepared spheroplasts. RESULTS: The MIC ranged from 12.5-50.0
      microg/mL, 5.0-40.0 mg/mL, and 2.5-10.0 mg/mL for benzydamine, lidocaine, and
      bupivacaine, respectively. The inhibitory activity of these concentrations could
      be detected with the fluorescent probe FUN-1 after incubation for 60 minutes. A
      very fast fungicidal activity was shown by 0.2, 50, and 30 mg/mL of benzydamine,
      lidocaine, and bupivacaine, respectively. CONCLUSIONS: At lower concentrations,
      the tested drugs have a fungistatic activity, due to yeast metabolic impairment,
      while at higher concentrations they are fungicidal, due to direct damage to the
      cytoplasmic membrane.

PMID- 10968596
TI  - Liberal diagnosis and treatment of intrauterine infection reduces early-onset
      neonatal group B streptococcal infection but not sepsis by other pathogens.
AB  - OBJECTIVE: Comparison of the incidence and case fatality of early-onset group B
      streptococcus sepsis and sepsis caused by other pathogens in neonates after
      change of management of intrauterine infection. METHODS: All infants delivered
      from 1988 through 1997 at a gestational age > or = 24 weeks with a birth weight >
      or = 500 gram without lethal congenital abnormalities were eligible for
      inclusion. Infants delivered by cesarean section before the onset of labor or
      rupture of membranes were excluded. During the first period (1988-1991)
      intrauterine infection was diagnosed by a temperature > 38 degrees C, during the
      second period (1992-1997) this diagnosis was made at a lower temperature (> or =
      37.8 degrees C) or by fetal tachycardia > or = 160/min. Treatment of intrauterine
      infection was similar during both periods with 3 x 2 gram amoxicillin and 1 x 240
      mg gentamicin every 24 hours intravenously during labor. Prophylactic treatment
      during labor was only given to women with a history of an earlier infant with
      early-onset group B streptococcus sepsis. RESULTS: During the first period 6,103
      infants were included, during the second period 8,504. Intrauterine infection was
      diagnosed and treated more often in the second period (7.1% vs. 2.6%). The
      incidence of early-onset group B streptococcus sepsis was significantly lower in
      the second period than in the first period [0.2% vs. 0.4%; OR 0.5 (0.3-0.9)] and
      survival without disability higher [80% vs. 52%; OR 4.5 (1.4-16.5)]. However, in
      both periods the overall incidence of neonatal sepsis (3.6% vs. 3.5%) and overall
      mortality because of sepsis (14.3% vs.13.1%) were similar. CONCLUSIONS: Although
      the early detection of clinical signs of intrauterine infection might have been
      effective for the prevention of serious sequelae of early-onset group B
      streptococcus sepsis the overall incidence and mortality from neonatal sepsis
      remained unchanged. Evaluation of preventive measures for early-onset group B
      streptococcus sepsis should always take the incidence of neonatal sepsis caused
      by other pathogens into account.

PMID- 10968597
TI  - Use of methergine for the prevention of postoperative endometritis in non
      elective cesarean section patients.
AB  - OBJECTIVE: Methergine increases constriction of uterine musculature which may
      facilitate sloughing of endometrial debris, close uterine vessels, and prevent
      post-cesarean endometritis. The objective of this study was to evaluate the
      efficacy of methergine in preventing endometritis in patients undergoing non
      elective cesarean section delivery. METHODS: Eighty patients undergoing non
      elective cesarean section were enrolled in a prospective randomized clinical
      trial of methergine (41) versus no methergine (39) administration during the
      postpartum period. The hospital records were abstracted after discharge to
      compare the postpartum course. RESULTS: There were no significant demographic
      differences between the two groups. The women receiving methergine had a
      significant reduction in the rate of postoperative endometritis (10% vs. 36%, P <
      0.005). In addition, the mean postoperative hemoglobin was significantly higher
      in the methergine treated group (P < 0.001). CONCLUSIONS: The use of methergine
      postpartum in women undergoing non-elective cesarean sections significantly
      reduces the incidence of postoperative endometritis and blood loss.

PMID- 10968598
TI  - Antenatal marijuana use is unrelated to sexually transmitted infections during
      pregnancy.
AB  - OBJECTIVE: This study evaluated the relationship between marijuana use and
      sexually transmitted diseases in pregnant women. METHODS: A retrospective review
      of clinic records over a 12-1/2 month period identified all women entering
      prenatal care. Eighty-six women using no illicit substance other than marijuana
      were compared to 441 drug-free women. The prevalence of gonorrhea, chlamydia,
      syphilis, human immunodeficiency virus, hepatitis B surface antigen, human
      papilloma virus, and herpes was ascertained. RESULTS: No significant differences
      were found in the prevalence of any single sexually transmitted disease between
      pregnant women who used marijuana and drug-free pregnant women. When the presence
      of one or more sexually transmitted disease was considered, again no difference
      was found. CONCLUSION: Marijuana use was not associated with sexually transmitted
      disease in pregnant women.

PMID- 10968599
TI  - Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal
      vaginal microbial flora of pregnant women.
AB  - OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the
      incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial
      flora graded as intermediate or BV and to investigate the effect of the
      antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of
      pregnant women in an antenatal clinic of a district general hospital. The
      subjects were 268 women who had abnormal vaginal microbial flora at first clinic
      visit by examination of a Gram-stained vaginal smear and 34 women with a normal
      vaginal flora. Two hundred and thirty-seven women were evaluable. Women with
      abnormal Gram-stained smears (graded as II or III) on clinic recall were
      randomised to receive treatment (intravaginal clindamycin cream) or placebo and
      followed to assess outcome of pregnancy, vaginal flora, and detection of
      Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal
      outcomes of pregnancy were not significantly different in treated and placebo
      groups by Chi square (P = 0.2). However, women with grade III flora responded
      better to clindamycin than women with grade II flora by numbers of abnormal
      outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic
      regression analysis model). This may be due to differences in vaginal bacterial
      species in these grades. Women whose abnormal vaginal flora had spontaneously
      returned to normal on follow-up and were therefore not treated (revertants) had
      as many abnormal outcomes as placebos suggesting that damage by abnormal
      bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening
      distinguishing grade II from grade III flora may be helpful in prescribing
      treatment other than clindamycin for women with grade II flora. Earlier diagnosis
      and treatment may be more effective in preventing an abnormal outcome, possibly
      as soon as pregnancy is diagnosed or even offered as a pre-conception screen.

PMID- 10968601
TI  - A study to determine the incidence and prevalence of newly discovered human
      immunodeficiency virus infection during the prenatal care period.
AB  - OBJECTIVES: This study asked the following questions: 1) Does HIV testing in
      pregnancy identify women who previously were not known to be HIV positive? 2)
      When in pregnancy are women identified as HIV infected? 3) Does HIV
      seroconversion occur during the prenatal care period? METHODS: Medical records of
      97 women from two primarily indigent care hospitals in Houston, TX who were found
      to be HIV positive at delivery were reviewed to determine if they had tested
      positive during the prenatal care period. Demographics and time of gestation of
      the prenatal testing also were recorded. The outcome measures were: 1) number of
      women found positive during prenatal care; 2) week of gestation at discovery of
      HIV positivity; and 3) number of women seroconverting between the initiation of
      prenatal care and delivery. RESULTS: Thirty women were known to be HIV positive
      prior to pregnancy. Fifty-six women were found to be positive during prenatal
      care and the seropositivity of 44 was discovered before the 34th week of
      pregnancy. Ten women were found to be positive at their first prenatal visit,
      which occurred after the 34th week. Date of testing was unknown for two women.
      Eleven women who received no prenatal care were found to be HIV positive at
      delivery. There were no seroconversions while women were under prenatal care.
      CONCLUSIONS: HIV testing at delivery did not find any HIV-positive women who had
      tested negative during prenatal care. Testing is very important for women who do
      not receive prenatal care. Making certain that high-risk women get into prenatal
      care also is very important.

PMID- 10968600
TI  - Detection of cytomegalovirus in the meconium of infected newborns by polymerase
      chain reaction.
AB  - OBJECTIVE: Congenital cytomegalovirus (CMV) infection is a leading cause of
      hearing loss and mental retardation throughout the world. Detection of the CMV
      DNA by polymerase chain reaction (PCR) offers a sensitive, rapid, and specific
      means of identification. Meconium, the stool formed in utero, may be an ideal
      specimen for CMV detection. The objective of this study was to develop a PCR
      based methodology for the detection of CMV in the meconium of neonates. METHODS:
      Meconium was collected from 10 newborn infants (seven with positive viral
      cultures and three uninfected infants born to CMV-seropositive mothers). For
      each, DNA was isolated from meconium by organic extraction and attachment to a
      DNA-binding matrix, and PCR was performed using amplimers specific for the major
      intermediate early (MIE) and late antigenic (LA) regions of CMV. RESULTS: Gel
      electrophoresis demonstrated an anticipated PCR product of 250 base pairs (bp)
      corresponding to the MIE region of CMV in all infected and positive control
      meconium samples. Furthermore, a single band of 150 bp corresponding to the LA
      region of CMV was also amplified in several of the infected infants. Conversely,
      no amplification of these antigenic regions was noted in either uninfected
      infants born to CMV-seropositive mothers or negative controls. CONCLUSIONS: CMV
      is present within the meconium of infected neonates and is readily detectable by
      PCR.

PMID- 10968602
TI  - Determinants of incident vulvovaginal candidiasis in human immunodeficiency virus
      positive women.
AB  - OBJECTIVE: Mucosal infections including vulvovaginal candidiasis are a common
      problem for women with human immunodeficiency virus (HIV) infection. Our
      objective was to determine which factors predict the development of symptomatic
      disease among HIV-infected women. MATERIALS AND METHODS: In a prospective study
      from 1991 to 1995, 205 HIV-positive women were evaluated every 6 months for
      occurrences of vulvovaginal candidiasis. Included in the study were all initially
      asymptomatic women, whether they were fungal-culture-positive or -negative at
      baseline. Excluded from the study were all women with symptomatic vulvovaginal
      candidiasis at the initial visit, those who developed trichomonas vaginitis at
      any visit, and those who used any antifungal agents. RESULTS: The risk of the
      development of vulvovaginal candidiasis did not differ between women who were
      asymptomatically colonized at baseline and those who were fungal-culture
      negative. However, the risk of developing vulvovaginal candidiasis was increased
      6.8 times for women with CD4 counts less than 200 cells/mm3 at baseline.
      CONCLUSIONS: Fungal culture is not predictive of the development of symptomatic
      vulvovaginal candidiasis. Women infected with HIV who have CD4 counts below 200
      cells/mm3 should be monitored more carefully for vulvovaginal candidiasis.

PMID- 10968603
TI  - Non-surgical management of post-cesarean endomyometritis associated with
      myometrial gas formation.
AB  - We present a case of post-cesarean delivery, nonclostridial endomyometritis in
      which uterine (myometrial) gas formation raised concern for myonecrosis and need
      for hysterectomy. The patient fully recovered without surgery. Myometrial gas
      formation in this setting and in an otherwise stable patient may be an
      insufficient reason for hysterectomy.

PMID- 10968606
TI  - Persistence of hexaconazole, a triazole fungicide in soils.
AB  - Persistence of hexaconazole (2-(2,4-dichlorophenyl)- 1-(1H-1,2,5-triazol-1-yl)
      hexan-2-ol) was studied in alluvial, red and black soils under flooded and
      nonflooded conditions. This fungicide was more persistent in all soils under
      flooded conditions than under nonflooded conditions and at 27 degrees C than at
      35 degrees C. Degradation of hexaconazole in sterilized and nonsterilized soils
      proceeded at identical rates indicating a minor role of micro-organisms in its
      degradation. The soil persistence of hexaconazole was not affected by the
      addition of wheat straw both under flooded and nonflooded conditions.

PMID- 10968605
TI  - An alternative supercritical fluid extraction system for aqueous matrices and its
      application in pesticides residue analysis.
AB  - Supercritical fluid extraction (SFE) is a rapid and convenient method for the
      isolation of organic compounds from environmental samples. This paper describes a
      supercritical carbon dioxide (CO2) extraction system that uses a newly designed
      extraction cell to recover organic compounds from an aqueous matrix. Analysis of
      the extracts by gas chromatography-electron capture detector (GC-ECD) indicated
      that the herbicide trifluralin (2,6-dinitro-N,N-dipropyl-4
      trifluoromethylaniline) could be quantitatively extracted by using the SFE system
      proposed with small amounts of sample. The percentage of recovery obtained with
      the SFE system described was twice as high as the result obtained using a
      conventional solid-phase extraction technique. Extraction by SFE was completed in
      a short period of time using a simple and low-cost home-made system that did not
      require the use of organic solvents.

PMID- 10968604
TI  - Gynecologic conditions and bacterial vaginosis: implications for the non-pregnant
      patient.
AB  - Bacterial vaginosis is characterized by a shift from the predominant
      lactobacillus vaginal flora to an overgrowth of anaerobic bacteria. Bacterial
      vaginosis is associated with an increased risk of gynecologic complications,
      including pelvic inflammatory disease, postoperative infection, cervicitis, human
      immunodeficiency virus (HIV), and possibly cervical intraepithelial neoplasia
      (CIN). The obstetrical risks associated with bacterial vaginosis include
      premature rupture of membranes, preterm labor and delivery, chorioamnionitis and
      postpartum endometritis. Despite the health risks associated with bacterial
      vaginosis and its high prevalence in women of childbearing age, bacterial
      vaginosis continues to be largely ignored by clinicians, particularly in
      asymptomatic women.

PMID- 10968607
TI  - In vitro study of oxytetracycline adsorption on activated charcoal.
AB  - In vitro adsorption experiments simulating pH in gastric environment and using
      Langmuir isotherm, showed that 408 mg of oxytetracycline was adsorbed per gram of
      activated charcoal. Langmuir isotherm fitted adsorption data better than a
      Freundlich isotherm. Freundlich isotherm showed a specific adsorption capacity of
      518 mg/g for activated charcoal. Both isotherm parameters indicated a strong
      oxytetracycline adsorption on activated charcoal in terms of quantity and binding
      strength. The results demonstrate that the concomitant use of oxytetracyline and
      activated charcoal should be avoided.

PMID- 10968608
TI  - Metolachlor persistence in laboratory and field soils under Indian tropical
      conditions.
AB  - Metolachlor [2-chloro-N-(2-methoxy-1-methylethyl)-2'-ethyl-6'- methyl
      acetanilide] dissipation under both field and laboratory conditions were studied
      during summer season in an Indian soil. Metolachlor was found to have moderate
      persistence with a half-life of 27 days in field. The herbicide got leached down
      to 15-30 cm soil layer and residues were found up to harvest day of the sunflower
      crop in both 0-15 cm and 15-30 cm soil layers. Metolachlor was found to be more
      persistent in laboratory studies conducted for 190 days. The rate of degradation
      was faster in soil under flooded partial anaerobic conditions as compared to
      aerobic soil with a half-life of 44.3 days. In aerobic soil, metolachlor was very
      stable with only 49% dissipation in 130 days. Residues remained in both the soils
      up to the end of the experimental period of 190 days.

PMID- 10968609
TI  - Seepage from deep bedded and poultry litter systems.
AB  - The work reported indicates that there could be a potential of ground water
      pollution by NO3-N from turkey facilities built on both sandy and clay soils. At
      four different depths (30.54, 61.08, 91.62, and 122.16 cm), the NO3-N levels for
      the clay soil were 1572, 497, 66, and 28 ppm, and those for the sandy soil were
      293, 425, 324, and 164 ppm, respectively. No significant P increases were
      observed but there did exist a significant increase of K in the topsoil for both
      clay and sandy turkey structures. The results show that swine hoop houses with
      less than three or four years of age may not pose a threat to groundwater
      pollution due to the leaching of nutrients. The only dairy feedlot sampled in
      this study, although it has been used for more than 20 years, did not show
      leaching of NO3-N and P. However, it did show a significantly elevated
      concentration of potassium in the topsoil, as compared to the background sample.
      More sites should be investigated to verify this.

PMID- 10968610
TI  - Salmonella enteritidis hilA gene fusion response after incubation in spent media
      from either S. enteritidis or a poultry Lactobacillus strain.
AB  - The purpose of this study was to determine if growth of a poultry probiotic
      lactobacilli strain can influence S. enteritidis virulence expression by
      measuring the response of a hilA-lacZY transcriptional fusion. beta-galactosidase
      activity was not detected when S. enteritidis was incubated in Lactobacillus
      spent medium (24 h growth, pH 4.1, 50.4 mM lactate) but was detectable in spent
      medium from 4 h growth cultures of Lactobacillus sp. (final OD of 0.213, pH 5.7,
      12 mM lactate) when pH and lactate were adjusted to that of the 24 h-pH 4 spent
      media levels. Adjusting the pH of the 24 h spent medium from 4 to 6, resulted in
      a measurable beta-galactosidase activity that was significantly higher than
      expression in LB broth. When S. enteritidis was grown in Salmonella-spent media
      (24 h growth, pH 4.2, 78 mM acetate), hilA expression was increased 4-fold over
      expression in the LB broth.

PMID- 10968611
TI  - Radionuclides in pinon pine (Pinus edulis) nuts from Los Alamos National
      Laboratory lands and the dose from consumption.
AB  - One of the dominant tree species growing within and around the eastern portion of
      Los Alamos National Laboratory (LANL), Los Alamos, NM, lands is the pinon pine
      (Pinus edulis). Pinon pine is used for firewood, fence posts, and building
      materials and is a source of nuts for food--the seeds are consumed by a wide
      variety of animals and are also gathered by people in the area and eaten raw or
      roasted. This study investigated the (1) concentration of 3H, 137Cs, 90Sr, totU,
      238Pu, 239,240Pu, and 241Am in soils (0- to 12-in. [31 cm] depth underneath the
      tree), pinon pine shoots (PPS), and pinon pine nuts (PPN) collected from LANL
      lands and regional background (BG) locations, (2) committed effective dose
      equivalent (CEDE) from the ingestion of nuts, and (3) soil to PPS to PPN
      concentration ratios (CRs). Most radionuclides, with the exception of 3H in
      soils, were not significantly higher (p < 0.10) in soils, PPS, and PPN collected
      from LANL as compared to BG locations, and concentrations of most radionuclides
      in PPN fromLANL have decreased over time. The maximum net CEDE (the CEDE plus two
      sigma minus BG) at the most conservative ingestion rate (10 lb [4.5 kg]) was
      0.0018 mrem (0.018 microSv); this is far below the International Commission on
      Radiological Protection (all pathway) permissible dose limit of 100 mrem (1000
      microSv). Soil-to-nut CRs for most radionuclides were within the range of default
      values in the literature for common fruits and vegetables.

PMID- 10968612
TI  - Phytoavailability and extractability of potassium, magnesium and manganese in
      calcareous soil amended with olive oil wastewater.
AB  - Land disposal of olive oil wastewater using it as a soil amendment requires a
      knowledge of the effects that its application may produce on the status of the
      mineral nutrients in the plant-soil system. A pot experiment using calcareous
      soil was performed in a growth chamber to examine the effects of olive oil
      wastewater on the availability and postharvest soil extractability of K, Mg and
      Mn. The experiment included 6 treatments: two rates of olive oil wastewater, two
      mineral fertilizer treatments containing K (which supplied K in amounts
      equivalent to the K supplied by the olive oil wastewater treatments), a K-free
      mineral fertilizer treatment, and a control. The pots were sown with ryegrass as
      the test plant, harvesting 3 times at intervals of one month. Olive oil
      wastewater has demonstrated a considerable capacity for supplying K that can be
      assimilated by the plant, tending in fact to surpass the mineral potassium
      fertilizer tested. The application of olive oil wastewater tends to reduce the
      concentration of Mg in the plant, similarly to the effect of adding mineral
      potassium fertilizer. An enhancement of Mn availability takes place in the soil
      amended with olive oil wastewater, which on occasion has produced Mn
      concentrations in plant that could be considered phytotoxic or at least
      excessive. After harvesting, we observed an increase in the amount of
      exchangeable K in soil with added industrial wastewater. However, these increases
      are lower than those in soil treated with mineral potassium fertilizer. The
      levels of exchangeable, carbonate-bound, organic-bound and residual Mg in soil
      were higher in treatments incorporating olive oil wastewater than in those with
      added mineral K, with the opposite tendency occurring in the amount of Fe-Mn
      oxides-bound Mg in soil. Treatments based on olive oil wastewater, especially in
      high doses, increased the amount of exchangeable and carbonate-bound Mn in soil,
      in comparison with treatments adding mineral fertilizers with or without K. In
      contrast, the addition of industrial wastewater caused a drop in the amount of Fe
      Mn oxides-bound and organic-bound Mn in soil.

PMID- 10968613
TI  - Perspectives in inorganic structural biology: solution structures of
      metalloproteins.
AB  - The achievements in the structural characterization in solution, through NMR
      spectroscopy, of proteins containing metal ions are reviewed and discussed. We
      call this branch "inorganic structural biology". The results of this approach are
      presented here for cytochrome b5, used in this paper as a case system. These
      results are discussed particularly in the light of their relevance for
      understanding the biological function of the proteins. Furthermore, the extension
      of the characterization to the internal motions and to the folding/unfolding
      processes, as well as the development of tools for structure prediction, are
      critically presented. The message is that the complete characterization of a
      biological molecule cannot be limited to a static description of the structure
      but it should go beyond, analyzing the internal motions occurring at various time
      scales as well as the behavior in different conditions, such as in the presence
      of denaturing agents.

PMID- 10968614
TI  - Characterisation of oxidised 7Fe dicluster ferredoxins with NMR spectroscopy.
AB  - Dicluster ferredoxins (Fds) from Sulfolobus acidocaldarius and Desulfovibrio
      africanus (FdIII) have been studied using 1H NMR. Both wild-type proteins contain
      a [3Fe-4S]+/0 and a [4Fe-4S]2+/+ cluster as isolated. The [4Fe-4S]2+/+ cluster
      (cluster II) is bound by cysteine residues arranged in a classic ferredoxin
      motif: CysI-(Xaa)2-CysII-(Xaa)2-CysIII-(Xaa)n-CysIV-Pro , whilst the binding
      motif of the [3Fe-4S]+/0 cluster (cluster I) has a non-ligating aspartic acid
      (Asp14) at position II, i.e. CysI-(Xaa)2-Asp-(Xaa)2-CysIII. D. africanus FdIII
      undergoes facile cluster transformation from the 7Fe form to the 8Fe form, but S.
      acidocaldarius Fd does not. Many factors determine the propensity of a cluster to
      undergo interconversion, including the presence, and correct orientation, of a
      suitable ligand. We have investigated this using 1H NMR by introducing a
      potential fourth ligand into the binding motif of cluster I of D. africanus
      FdIII. Asp14 has been mutated to cysteine (D14C), glutamic acid (D14E) and
      histidine (D14H). Cluster incorporation was performed in vitro. The cluster types
      present were identified from the chemical shift patterns and temperature
      dependent behaviour of the hyperfine-shifted resonances. Factors influencing
      cluster ligation and cluster interconversion, in vitro, are discussed.
      Furthermore, the data have established that the residue at position II in the
      cluster binding motif of cluster I is influential in determining the chemical
      shift pattern observed for a [3Fe-4S]+ cluster when a short/symmetric binding
      motif is present. Based on this, a series of rules for characterising the 1H NMR
      chemical shifts of mono- and di-cluster [3Fe-4S]+ cluster-containing ferredoxins
      is given.

PMID- 10968615
TI  - Probing local thermal stabilities of bovine, horse, and tuna ferricytochromes c
      at pH 7.
AB  - Correlation between the flexibility of the Met80 loop (residues 75-86) and the
      local stabilities of native ferricytochromes c from horse, bovine, and tuna was
      examined. By monitoring the heme bands versus temperature, absorption changes
      associated with altered ligation in the alkaline isomers were observed. In
      addition, the intensity of the 695-nm absorption band, which is associated with
      the heme-crevice stability, decreased with increasing temperature and exhibited
      biphasic temperature dependence, with transition temperatures (Tc) at 35 degrees
      C in tuna c, 55 degrees C in horse c, and 58 C in bovine c. Since the heme
      crevice plays a key role in the thermal stabilities of cytochromes c, their
      susceptibility to proteolytic attack was examined as a function of temperature.
      Proteolytic digestion, which requires local conformational instability, revealed
      that the local stabilities of the cytochromes follow the order: bovine > horse >>
      tuna, and increased digestion occurred at temperatures close to the 695-nm Tc for
      each protein. This is consistent with the actual substitution of the Met80 ligand
      above the 695-nm Tc, which is reflected in the thermodynamic parameters for the
      two phases. Also, tuna c, unlike horse and bovine c, exhibits different 695-nm
      (35 degrees C) and Soret (approximately 46 degrees C) Tc values, but its local
      stability is controlled by the transition detected at 695 nm. The combined
      spectroscopic and proteolysis results clearly indicate that the flexibility of
      the Met80 loop determines the local stability of cytochromes c.

PMID- 10968616
TI  - 19F NMR study of protein-induced rhombic perturbations on the electronic
      structure of the active site of myoglobin.
AB  - A novel C2-symmetric ring-fluorinated hemin, 13,17-bis(2-carboxyethyl)-2,8,12,18
      tetramethyl-3,7-difluoroporphyrin atoiron(III), has been synthesized and was
      incorporated into sperm whale apomyoglobin to investigate protein-induced rhombic
      perturbations on the electronic structure of the active site of myoglobin (Mb)
      using 19F NMR spectroscopy. NMR signals for 19F atoms introduced as substituents
      on the present heme in ferrous low-spin and high-spin and ferric low-spin
      complexes have been observed and their shifts sharply reflect not only the
      electronic nature of the heme iron, but also in-plane asymmetry of the heme
      electronic structure. The two-fold symmetric electronic structure of the ring
      fluorinated hemin is clearly manifested in the 19F and 1H NMR spectra of its
      dicyano complex. The chemical equivalence of the two fluorine atoms of the heme
      is removed in the active site of myoglobin and the splitting of the two 19F NMR
      signals provides a quantitative probe for characterizing the rhombic perturbation
      of the heme electronic structure induced by the heme-protein interaction. The in
      plane asymmetry of heme electronic structures in carbon-monoxy and deoxy Mbs have
      been analyzed for the first time on the basis of the shift difference between the
      two 19F NMR signals of the heme and is interpreted in terms of iron-ligand
      binding and/or the orbital ground state of the heme. A potential utility of 19F
      NMR, combined with the use of a symmetric fluorinated hemin, in characterizing
      the heme electronic structure of myoglobin in a variety of iron oxidation, spin,
      and ligation states, is presented.

PMID- 10968617
TI  - Reaction of DNA oligonucleotides with [Pt(dien)GSMe]2+ (GSMe = S-methylated
      glutathione) and cis-[Pt(NH3)2(GSMe)2]2+: evidence of oligonucleotide platination
      via sulfur-coordinated platinum intermediates.
AB  - To study the possibility of DNA platination via platinum-sulfur coordinated
      intermediates, the reactions of the complexes [Pt(dien)GSMe]2+ (GSMe=S-methylated
      glutathione) and cis-[Pt(NH3)2(GSMe)2]2+ with the synthetic oligonucleotides
      d(ATATGCATAT), d(ATTACCGGTAAT), and d(ATCCTATTTTTTTTAGGAT) have been
      investigated. The reactions were studied using FPLC, NMR, and mass spectrometry.
      It was found that the sulfur atom of the platinum-thioether adduct is substituted
      by these oligonucleotides. For the reactions with [Pt(dien)GSMe]2+ at 310 K, half
      lives were determined to be t 1/2 =147+/-7 h for d(ATATGCATAT), t 1/2 =84+/-4 h)
      for d(ATTACCGGTAAT), and t 1/2 = 21+/-1 h for d(ATCCTATTTTTTTTAGGAT. This study
      clearly shows that it is indeed possible for oligonucleotides to be platinated
      via Pt-thioether coordinated intermediates. The rates at which such substitutions
      occur, however, makes it improbable that such a mechanism contributes
      significantly to the antitumor activity of cisplatin.

PMID- 10968618
TI  - Synthesis, spectroscopic, and structural characterization of the first aqueous
      cobalt(II)-citrate complex: toward a potentially bioavailable form of cobalt in
      biologically relevant fluids.
AB  - Citric acid represents a class of carboxylic acids present in biological fluids
      and playing key roles in biochemical processes in bacteria and humans. Its
      ability to promote diverse coordination chemistries in aqueous media, in the
      presence of metal ions known to act as trace elements in human metabolism,
      earmarks its involvement in a number of physiological functions. Cobalt is known
      to be a central element of metabolically important biomolecules, such as B12, and
      therefore its biospeciation in biological fluids constitutes a theme worthy of
      chemical and biological perusal. In an effort to unravel the aqueous chemistry of
      cobalt in the presence of a physiologically relevant ligand, citrate, the first
      aqueous, soluble, mononuclear complex has been synthesized and isolated from
      reaction mixtures containing Co(II) and citrate in a 1:2 molar ratio at pH
      approximately 8. The crystalline compound (NH4)4[Co(C6H5O7)2] (1) has been
      characterized spectroscopically (UV/vis, EPR) and crystallographically. Its X-ray
      structure consists of a distorted octahedral anion with two citrate ligands
      fulfilling the coordination requirements of the Co(II) ion. The magnetic
      susceptibility measurements of 1 in the range from 6 to 295 K are consistent with
      a high-spin complex containing Co(II) with a ground state S=3/2. Corroborating
      this result is the EPR spectrum of 1, which shows a signal consistent with the
      presence of a Co(II) system. The spectroscopic and structural properties of the
      complex signify its potential biological relevance and participation in
      speciation patterns arising under conditions consistent with those employed for
      its synthesis and isolation.

PMID- 10968619
TI  - Mossbauer, EPR, and MCD studies of the C9S and C42S variants of Clostridium
      pasteurianum rubredoxin and MDC studies of the wild-type protein.
AB  - Rubredoxins contain a mononuclear iron tetrahedrally coordinated by four
      cysteinyl sulfurs. We have studied the wild-type protein from Clostridium
      pasteurianum and two mutated forms, C9S and C42S, in the oxidized and reduced
      states, with Mossbauer, integer-spin EPR, and magnetic circular dichroism (MCD)
      spectroscopies. The Mossbauer spectra of the ferric C42S and C9S mutant forms
      yielded zero-field splittings, D = 1.2 cm(-1), that are about 40% smaller than
      the D-value of the wild-type protein. The 57Fe hyperfine coupling constants were
      found to be ca. 8% larger than those of the wild-type proteins. The present study
      also revealed that the ferric wild-type protein has delta=0.24+/-0.01 mm/s at 4.2
      K rather than delta = 0.32 mm/s as reported in the literature. The Mossbauer
      spectra of both dithionite-reduced mutant proteins revealed the presence of two
      ferrous forms, A and B. These forms have isomer shifts delta = 0.79 mm/s at 4.2
      K, consistent with tetrahedral Fe2+(Cys)3(O-R) coordination. The zero-field
      splittings of the two forms differ substantially; we found D = -7+/-1 cm(-1), E/D
      = 0.09 for form A and D = +6.2+/-1.3 cm(-1), E/D = 0.15 for form B. Form A
      exhibits a well-defined integer-spin EPR signal; from studies at X- and Q-band we
      obtained g(z) = 2.08+/-0.01, which is the first measured g-value for any ferrous
      rubredoxin. It is known from X-ray crystallographic studies that ferric C42S
      rubredoxin is coordinated by a serine oxygen. We achieved 75% reduction of C42S
      rubredoxin by irradiating an oxidized sample at 77 K with synchrotron X-rays; the
      radiolytic reduction produced exclusively form A, suggesting that this form
      represents a serine-bound Fe2+ site. Studies in different buffers in the pH 6-9
      range showed that the A:B ratios, but not the spectral parameters of A and B, are
      buffer dependent, but no systematic variation of the ratio of the two forms with
      pH was observed. The presence of glycerol (30-50 % v/v) was found to favor the B
      form. Previous absorption and circular dichroism studies of reduced wild-type
      rubredoxin have suggested d-d bands at 7400, 6000, and 3700 cm(-1). Our low
      temperature MCD measurements place the two high-energy transitions at ca. 5900
      and 6300 cm(-1); a third d-d transition, if present, must occur with energy lower
      than 3300 cm(-1). The mutant proteins have d-d transitions at slightly lower
      energy, namely 5730, 6100 cm(-1) in form A and 5350, 6380 cm(-1) in form B.

PMID- 10968620
TI  - Ternary Gd(III)L-HSA adducts: evidence for the replacement of inner-sphere water
      molecules by coordinating groups of the protein. Implications for the design of
      contrast agents for MRI.
AB  - Two novel gadolinium(III) chelates based on the structure of the heptadentate
      macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand
      have been synthesized and their relaxometric and luminescent properties
      thoroughly investigated. They contain two water molecules in the inner
      coordination sphere in fast exchange with the bulk solvent and bear either a p
      bromobenzyl or a p-phosphonatomethylbenzanilido substituent for promoting further
      interaction with macromolecular substrates. Upon interaction with human serum
      albumin the expected relaxation enhancement is not observed owing to displacement
      of the two inner-sphere water molecules of the complexes by a donor atom (likely
      from a carboxylate group) on the protein and possibly the phosphate anion of the
      buffered solution, respectively. We modeled the observed behavior by measuring
      the decrease of the relaxation rate of the water protons upon addition of
      malonate anion to aqueous solutions of the complexes. Conversely, no change in
      the hydratation state of the Gd(III) center for both complexes has been observed
      when the substrate for the formation of the macromolecular adduct is represented
      by poly-beta-cyclodextrin.

PMID- 10968621
TI  - Time-dependent interactions of platinum(II) complexes with 5'-GMP under simulated
      physiological conditions studies by capillary electrophoresis.
AB  - The binding behaviour as well as the time-dependent reaction of five platinum(II)
      complexes with 5'-GMP have been investigated by capillary electrophoresis under
      simulated physiological conditions referred to chloride concentration, pH and
      temperature. Different amine ligands influenced the binding properties towards 5'
      GMP and resulted in different half-times of the overall reaction. Complexes with
      bidentate ligands reacted faster with the monophosphate compared to complexes
      with monodentate ligands. Complexes consisting of two monodentate
      hydroxyethylamine ligands reacted very slowly owing to a competitive
      intramolecular reaction of the hydroxyethyl residues, which was proven by NMR
      investigations. Reducing the number of hydroxyethyl residues increased the half
      times of the reactions. Moreover, the major adducts formed with 5'-GMP were
      identified by MALDI-MS analysis.

PMID- 10968622
TI  - The 1.9 A crystal structure of the "as isolated" rubrerythrin from Desulfovibrio
      vulgaris: some surprising results.
AB  - Rubrerythrin is a non-heme iron dimeric protein isolated from the sulfate
      reducing bacterium Desulfovibrio vulgaris. Each monomer has one mononuclear iron
      center similar to rubredoxin and one dinuclear metal center similar to
      hemerythrin or ribonucleotide reductase. The 1.88 A X-ray structure of the "as
      isolated" molecule and a uranyl heavy atom derivative have been solved by
      molecular replacement techniques. The resulting model of the native "as isolated"
      molecule, including 164 water molecules, has been refined giving a final R factor
      of 0.197 (R(free) = 0.255). The structure has the same general protein fold,
      domain structure, and dimeric interactions as previously found for rubrerythrin
      [1, 2], but it also has some interesting undetected differences at the metal
      centers. The refined model of the protein structure has a cis peptide between
      residues 78 and 79. The Fe-Cys4 center has a previously undetected strong seventh
      N-H...S hydrogen bond in addition to the six N-H...S bonds usually found in
      rubredoxin. The dinuclear metal center has a hexacoordinate Fe atom and a
      tetracoordinate Zn atom. Each metal is coordinated by a GluXXHis polypeptide
      chain segment. The Zn atom binds at a site distinctly different from that found
      in the structure of a diiron rubrerythrin. Difference electron density for the
      uranyl derivative shows an extremely large peak adjacent to and replacing the Zn
      atom, indicating that this particular site is capable of binding other atoms.
      This feature/ability may give rise to some of the confusing activities ascribed
      to this molecule.

PMID- 10968623
TI  - Probing magnetic properties of the reduced [2Fe-2S] cluster of the ferredoxin
      from Arthrospira platensis by 1H ENDOR spectroscopy.
AB  - The 1H electron nuclear double resonance (ENDOR) spectra in frozen solutions of
      the reduced [2Fe-2S] cluster in ferredoxin from Arthrospira (Spirulina) platensis
      have been measured at low temperatures (5-20 K) and simulated using orientational
      selection methods. The analysis confirmed the existence of a single paramagnetic
      species with iron valence states II and III connected uniquely to the cluster
      irons. The experimental ENDOR spectra were fitted to a model including the spin
      distribution on the centre, the orientation of the g-matrix, and the isotropic
      and anisotropic hyperfine couplings of the nearest protons in the
      crystallographically determined structure. In order to partially simulate ENDOR
      line shapes, a statistical distribution of the corresponding torsion angles
      between the Fe(III) centre and one of the beta-CH2 protons was introduced. From
      the analysis, four of the larger hyperfine couplings found were assigned to the
      cysteine beta-protons near the Fe(III) ion of the cluster, with isotropic
      hyperfine couplings ranging from 1.6 to 4.1 MHz. The spin distribution on the two
      iron ions was estimated to be +1.85 for the Fe(III) ion and -0.9 for the Fe(II)
      ion. The Fe(III) ion was identified as being coordinated to the cysteine ligands
      Cys49 and Cys79, confirming previous NMR results. The direction of the g-tensor
      with respect to the cluster was deduced. The g1-g2 plane is parallel to the
      planes through each iron and its adjacent cysteine sulfurs; the g2-g3 plane is
      nearly perpendicular to the latter planes and deviates by 25 degrees from the
      FeSSFe plane. The g1 direction is dominated by the bonding geometry of Fe(II) and
      does not align with the Fe(II)-Fe(III) vector.

PMID- 10968625
TI  - Fruiting body production in Basidiomycetes.
AB  - Mushroom cultivation presents an economically important biotechnological industry
      that has markedly expanded all over the world in the past few decades. Mushrooms
      serve as delicacies for human consumption and as nutriceuticals, as "food that
      also cures". Mushrooms, the fruiting bodies of basidiomycetous fungi, contain
      substances of various kinds that are highly valued as medicines, flavourings and
      perfumes. Nevertheless, the biological potential of mushrooms is probably far
      from exploited. A major problem up to now is that only a few species can be
      induced to fruit in culture. Our current knowledge on the biological processes of
      fruiting body initiation and development is limited and arises mostly from
      studies of selected model organisms that are accessible to molecular genetics. A
      better understanding of the developmental processes underlying fruiting in these
      model organisms is expected to help mushroom cultivation of other basidiomycetes
      in the future.

PMID- 10968624
TI  - Novel structure and redox chemistry of the prosthetic groups of the iron-sulfur
      flavoprotein sulfide dehydrogenase from Pyrococcus furiosus; evidence for a [2Fe
      2S] cluster with Asp(Cys)3 ligands.
AB  - The consecutive structural genes for the iron-sulfur flavoenzyme sulfide
      dehydrogenase, sudB and sudA, have been identified in the genome of Pyrococcus
      furiosus. The translated sequences encode a heterodimeric protein with an alpha
      subunit, SudA, of 52598 Da and a beta-subunit, SudB, of 30686 Da. The alpha
      subunit carries a FAD, a putative nucleotide binding site for NADPH, and a [2Fe
      2S]2+,+ prosthetic group. The latter exhibit EPR g-values, 2.035, 1.908, 1.786,
      and reduction potential, Em,8 = +80 mV, reminiscent of Rieske-type clusters;
      however, comparative sequence analysis indicates that this cluster is coordinated
      by a novel motif of one Asp and three Cys ligands. The motif is not only found in
      the genome of hyperthermophilic archaea and hyperthermophilic bacteria, but also
      in that of mesophilic Treponema pallidum. The beta-subunit of sulfide
      dehydrogenase contains another FAD, another putative binding site for NADPH, a
      [3Fe-4S]+,0 cluster, and a [4Fe-4S]2+,+ cluster. The 3Fe cluster has an unusually
      high reduction potential, Em,8 = +230 mV. The reduced 4Fe cluster exhibits a
      complex EPR signal, presumably resulting from magnetic interaction of its S = 1/2
      spin with the S=2 spin of the reduced 3Fe cluster. The 4Fe cluster can be reduced
      with deazaflavin/EDTA/light but not with sodium dithionite; however, it is
      readily reduced with NADPH. SudA is highly homologous to KOD1-GO-GAT (or KOD1
      GltA), a single-gene encoded protein in Pyrococcus kodakaraensis, which has been
      putatively identified as hyperthermophilic glutamate synthase. However, P.
      furiosus sulfide dehydrogenase does not have glutamate synthase activity. SudB is
      highly homologous to HydG, the gamma-subunit of P. furiosus NiFe hydrogenase. The
      latter enzyme also has sulfide dehydrogenase activity. The P. furiosus genome
      contains a second set of consecutive genes, sudY and sudX, with very high
      homology to the sudB and sudA genes, and possibly encoding a sulfide
      dehydrogenase isoenzyme. Each subunit of sulfide dehydrogenase is a primary
      structural paradigm for a different class of iron-sulfur flavoproteins.

PMID- 10968626
TI  - Ice crystallization by Pseudomonas syringae.
AB  - Several bacterial species can serve as biological ice nuclei. The best
      characterized of these is Pseudomonas syringae, a widely distributed bacterial
      epiphyte of plants. These biological ice nuclei find various applications in
      different fields, but an optimized production method was required in order to
      obtain the highly active cells which may be exploited as ice nucleators. The
      results presented here show that P. syringae cells reduce supercooling of liquid
      or solid media and enhance ice crystal formation at sub-zero temperatures, thus
      leading to a remarkable control of the crystallization phenomenon and a potential
      for energy savings. Our discussion focuses on recent and future applications of
      these ice nucleators in freezing operations, spray-ice technology and
      biotechnological processes.

PMID- 10968627
TI  - Utilisation of saccharides in extruded domestic organic waste by Clostridium
      acetobutylicum ATCC 824 for production of acetone, butanol and ethanol.
AB  - Domestic organic waste (DOW) collected in The Netherlands was analysed and used
      as substrate for acetone, butanol and ethanol (ABE) production. Two different
      samples of DOW, referred to as fresh DOW and dried DOW, were treated by extrusion
      in order to expand the polymer fibres present and to obtain a homogeneous
      mixture. The extruded material was analysed with respect to solvent and hot water
      extractives, uronic acids, lignin, sugars and ash. The total sugar content in the
      polymeric fractions of the materials varied from 27.7% to 39.3% (w/w), in which
      glucose represented the 18.4 and 25.1% of the materials, for fresh and dried DOW,
      respectively. The extruded fresh DOW was used as substrate for the ABE
      fermentation by the solventogenic strain Clostridium acetobutylicum ATCC 824.
      This strain was grown on a suspension of 10% (w/v) DOW in demineralised water
      without further nutrient supplement. This strain produced 4 g ABE/100 g extruded
      DOW. When C. acetobutylicum ATCC 824 was grown on a suspension of 10% (w/v) DOW
      hydrolysed by a combination of commercial cellulases and beta-glucosidases, the
      yield of solvents increased to 7.5 g ABE/100 g extruded DOW. The utilisation of
      sugar polymers in both hydrolysed and non-hydrolysed DOW was determined, showing
      that only a small proportion of the polymers had been consumed by the bacteria.
      These results indicate that growth and ABE production on DOW is mainly supported
      by soluble saccharides in the medium.

PMID- 10968628
TI  - The use of silica gel prepared by sol-gel method and polyurethane foam as
      microbial carriers in the continuous degradation of phenol.
AB  - A mixed microbial culture was immobilized by entrapment into silica gel (SG) and
      entrapment/ adsorption on polyurethane foam (PU) and ceramic foam. The phenol
      degradation performance of the SG biocatalyst was studied in a packed-bed reactor
      (PBR), packed-bed reactor with ceramic foam (PBRC) and fluidized-bed reactor
      (FBR). In continuous experiments the maximum degradation rate of phenol (q(s)max)
      decreased in the order: PBRC (598 mg l(-1) h(-1)) > PBR (PU, 471 mg l(-1)h(-1)) >
      PBR(SG, 394 mg l(-1) h(-1)) > FBR (PU, 161 mg l(-1) h(-1)) > FBR (SG, 91 mg l(-1)
      h(-1)). The long-term use of the SG biocatalyst in continuous phenol degradation
      resulted in the formation of a 100-200 microm thick layer with a high cell
      density on the surface of the gel particles. The abrasion of the surface layer in
      the FBR contributed to the poor degradation performance of this reactor
      configuration. Coating the ceramic foam with a layer of cells immobilized in
      colloidal SiO2 enhanced the phenol degradation efficiency during the first 3 days
      of the PBRC operation, in comparison with untreated ceramic packing.

PMID- 10968629
TI  - Purification and characterization of a thermostable esterase from the moderate
      thermophile Bacillus circulans.
AB  - The thermostable esterase from the moderate thermophile Bacillus circulans was
      purified to homogeneity using a four-step procedure. Esterase activity was
      associated with a protein of molecular mass 95 kDa, composed of three identical
      subunits of 30 kDa. The esterase activity was thermostable with a maximum
      activity at 55 degrees C using initial rate assay. The half-inactivation
      temperature was 71 degrees C after a 1-h treatment, which compared favorably to
      that of other enzymes. Activity at temperatures of 30-37 degrees C was high
      (about half of maximum), making this new enzyme very attractive for applications
      in this moderate temperature range. The esterase also showed high activity at a
      rather alkaline pH (higher than 10). The specificity pattern showed a marked
      specificity for mid-chain-length fatty acids (3-8 carbon atoms), which classified
      the enzyme as a carboxylesterase.

PMID- 10968630
TI  - A genetically modified solvent-tolerant bacterium for optimized production of a
      toxic fine chemical.
AB  - The aim of the study was to investigate whether toxic fine chemical production
      can be improved using the solvent-tolerant Pseudomonas putida S12 in a two-liquid
      phase system consisting of aqueous media and a water-immiscible octanol phase
      with production of 3-methylcatechol from toluene as the model conversion. For
      this purpose the genes involved in this conversion, todC1C2BAD from P. putida F1,
      were introduced into P. putida S12 with high stable expression. Production of 3
      methylcatechol was monitored in batch incubations with different media using a
      single medium and a two-liquid medium-octanol system. The maximum concentration
      of 3-methylcatechol increased two-fold using the two-liquid medium-octanol
      system, irrespective of the selected medium.

PMID- 10968631
TI  - Analysis of the Thiocapsa pfennigii polyhydroxyalkanoate synthase: subcloning,
      molecular characterization and generation of hybrid synthases with the
      corresponding Chromatium vinosum enzyme.
AB  - The PHA synthase structural gene of Thiocapsa pfennigii was identified and
      subcloned on a 2.8-kbp BamHI restriction fragment, which was cloned recently from
      a genomic 15.6-kbp EcoRI restriction fragment. Nucleotide sequence analysis of
      this fragment revealed three open reading frames (ORFs), representing coding
      regions. Two ORFs encoded for the PhaE (Mr 40,950) and PhaC (Mr 40,190) subunits
      of the PHA synthase from T. pfennigii and exhibited high homology with the
      corresponding proteins of the Chromatium vinosum (52.8% and 85.2% amino acid
      identity) and the Thiocystis violacea (52.5% and 82.4%) PHA synthases,
      respectively. This confirmed that the T. pfennigii PHA synthase was composed of
      two different subunits. Also, with respect to the molecular organization of phaE
      and phaC, this region of the T. pfennigii genome resembled very much the
      corresponding regions of C. vinosum and of Thiocystis violacea. A recombinant
      strain of Pseudomonas putida, which overexpressed phaE and phaC from T.
      pfennigii, was used to isolate the PHA synthase by a two-step procedure including
      chromatography on Procion Blue H-ERD and hydroxyapatite. The isolated PHA
      synthase consisted of two proteins exhibiting the molecular weights predicted for
      PhaE and PhaC. Hybrid PHA synthases composed of PhaE from T. pfennigii and PhaC
      from C. vinosum and vice versa were constructed and functionally expressed in a
      PHA-negative mutant of P. putida; and the resulting PHAs were analyzed.

PMID- 10968632
TI  - Coexpression of the Bacillus pumilus beta-xylosidase (xynB) gene with the
      Trichoderma reesei beta xylanase 2 (xyn2) gene in the yeast Saccharomyces
      cerevisiae.
AB  - The xynB gene encoding the Bacillus pumilus beta-xylosidase was expressed
      separately and jointly with the Trichoderma reesei beta-xylanase (xyn2) gene in
      the yeast Saccharomyces cerevisiae. Both genes were placed under the
      transcriptional control of the glucose-derepressible alcohol dehydrogenase 2
      promoter (ADH2p) and terminator (ADH2T) sequences. The xynB gene was fused in
      frame to the yeast mating factor alpha1 secretion sequence (MFalpha1s) to effect
      secretion in S. cerevisiae. The fusion protein was designated Xlo1. Xlo1 produced
      in S. cerevisiae exhibited low affinity for xylobiose, but eventually hydrolyzed
      xylobiose and xylotriose to the monomeric constituent, D-xylose. Coproduction of
      Xyn2 and Xlo1 by S. cerevisiae led to a 25% increase in the amount of reducing
      sugars released from birchwood xylan compared to S. cerevisiae producing only the
      Xyn2 beta-xylanase. However, no D-xylose was produced from birchwood xylan,
      presumably due to very low Xlo1 beta-xylosidase activity and its low affinity for
      xylobiose.

PMID- 10968633
TI  - Inhibition of Clostridium butyricum by 1,3-propanediol and diols during glycerol
      fermentation.
AB  - 1,3-Propanediol inhibition during glycerol fermentation to 1,3-propanediol by
      Clostridium butyricum CNCM 1211 has been studied. The initial concentration of
      the 1,3-propanediol affected the growth of the bacterium more than the glycerol
      fermentation. mu(max) was inversely proportional to the initial concentration of
      1,3-propanediol (0-65 g l(-1)). For glycerol at 20 g l(-1), the growth and
      fermentation were completely stopped at an initial 1,3-propanediol concentration
      of 65 g l(-1). However, for an initial 1,3-propanediol concentration of 50 g l(
      1) and glycerol at 70 g l(-1), the final concentration (initial and produced) of
      1,3-propanediol reached 83.7 g l(-1)(1.1 M), with complete consumption of the
      glycerol. Therefore, during the fermentation, the strain tolerated a 1,3
      propanediol concentration higher than the initial inhibitory concentration (65 g
      l(-1)). The addition of 1,2-propanediol or 2,3-butanediol (50 g l(-1)) in the
      presence of glycerol (50-100 g l(-1)), showed that 2-diols reduced the mu(max) in
      a similar way to 1,3-propanediol. The measurement of the osmotic pressure of
      glycerol solutions, diols and diol/glycerol mixtures did not indicate any
      differences between these compounds. The hypothesis of diol inhibition was
      discussed. Taking into account the strain tolerance of highly concentrated 1,3
      propanediol during fermentation, the fermentation processes for optimising
      production were considered.

PMID- 10968634
TI  - Changes in the physiological and agricultural characteristics of peat-based
      Bradyrhizobium japonicum inoculants after long-term storage.
AB  - Commercial soybean inoculants processed with sterilised peat and stored at 20
      degrees C for 1-8 years were used as experimental materials to assess the changes
      in the physiological activity of Bradyrhizobium japonicum after storage. Viable
      counts decreased and physiological characteristics of the bacterium changed
      during storage, with an increase in the time taken for colony appearance on a
      medium without yeast extract, an increase in the lag time for nodule appearance
      on soybean grown in glass tubes and a decrease in survival on seeds. All the
      inoculants produced a significant increase in grain yield in a field experiment.
      The percentage of efficient cells in the field (relative to the plate counts)
      decreased as the length of storage increased. These results suggest that the
      physiological activity of B. japonicum cells changes after storage. Practical
      implications for inoculant quality control are discussed.

PMID- 10968635
TI  - Metabolic characterization of high- and low-yielding strains of Penicillium
      chrysogenum.
AB  - A recently developed method for analyzing metabolic networks using 13C-labels was
      employed for investigating the metabolism of a high- and a low-yielding strain of
      Penicillium chrysogenum. Under penicillin-producing conditions, the flux through
      the pentose phosphate (PP) pathway in the high- and the low-yielding strains was
      estimated to 70 and 66, respectively. When the high-yielding strain was
      cultivated in a medium without the penicillin side chain precursor, phenoxyacetic
      acid, the PP pathway flux was estimated as 71. Thus, in all three experiments,
      the flux through the PP pathway was almost constant with an average value of 69+/
      3, and the method therefore allows for a very reproducible estimation of the PP
      pathway flux. Phenoxyacetic acid was found to be a source of cytosolic acetyl-CoA
      and thereby a source of precursors for the biosynthesis of 2-aminoadipic acid,
      which is a central amino acid in penicillin biosynthesis. However, the labeling
      patterns also indicated the presence of an unrecognized pathway to cytosolic
      acetyl-CoA.

PMID- 10968636
TI  - Accumulation and mobilization of storage lipids by Rhodococcus opacus PD630 and
      Rhodococcus ruber NCIMB 40126.
AB  - The time course of the accumulation of triacylglycerols (TAGs) in Rhodococcus
      opacus PD630 or of TAGs plus polyhydroxyalkanoates (PHA) in Rhodococcus ruber
      NCIMB 40126 with gluconate or glucose as carbon source, respectively, was
      studied. In addition, we examined the mobilization of these storage compounds in
      the absence of a carbon source. R. opacus accumulated TAGs only after the
      exhaustion of ammonium in the medium, and, with a fixed concentration of the
      carbon source, the amounts of TAGs in the cells increased with decreasing
      concentrations of ammonium in the medium. When these cells were incubated in the
      absence of an additional carbon source, about 90% of these TAGs were mobilized
      and used as endogenous carbon source, particularly if ammonium was available. R.
      ruber accumulated a copolyester consisting of 3-hydroxybutyrate and 3
      hydroxyvalerate already during the early exponential growth phase, whereas TAGs
      were synthesized and accumulated mainly during the late exponential and
      stationary growth phases. In the stationary growth phase, synthesis of TAGs
      continued, whereas PHA was partially mobilized. In the absence of an additional
      carbon source but in the presence of ammonium, mobilization of TAGs started first
      and was then paralleled by the mobilization of PHA, resulting in an approximately
      90% and 80% decrease of these storage compounds, respectively. During the
      accumulation phase, interesting shifts in the composition of the two storage
      compounds occurred, indicating that the substrates of the PHA synthase and the
      TAG synthesizing enzymes were provided to varying extents, depending on whether
      the cells were in the early or late exponential or in the stationary growth
      phase.

PMID- 10968637
TI  - Kinetic analysis of oil biosynthesis by an arachidonic acid-producing fungus,
      Mortierella alpina 1S-4.
AB  - Kinetic analysis of arachidonic acid (AA)-oil biosynthesis by Mortierella alpina
      1S-4 growing under lipid-accumulating (LN medium) and non-lipid-accumulating (HN
      medium) conditions was investigated and compared with industrial AA fermentation.
      Various kinetic parameters of these cultivation processes demonstrate a
      characteristic pattern of the lipogenesis in this fungus, where growth phase,
      phase of oil accumulation and phase of AA synthesis are distinct from each other.
      The fungus utilizing LN medium synthesized 32.3 g fatty acid 100 g(-1) glucose on
      the 4th day of cultivation and reached the maximum daily fatty acid accumulation
      (expressed as differential specific rate qD(FA/B)) of 9.5%. Our results also
      indicate that a qD(FA/B) value of about 2.5% might be critical for lipid
      overproduction in M. alpina. AA was rapidly incorporated into triacylglycerols
      (90% of total AA) at the later cultivation phase and overall AA yield was
      directly related to the total yield of fatty acid.

PMID- 10968638
TI  - Artificial biofilm model--a useful tool for biofilm research.
AB  - For biofilm studies, artificial models can be very helpful in studying processes
      in hydrogels of defined composition and structure. Two different types of
      artificial biofilm models were developed. Homogeneous agarose beads (50-500
      microm diameter) and porous beads (260 microm mean diameter) containing pores
      with diameters from 10 to 80 microm (28 microm on average) allowed the embedding
      of cells, particles and typical biofilm matrix components such as proteins and
      polysaccharides. The characterisation of the matrix structures and of the
      distribution of microorganisms was performed by confocal laser scanning
      microscopy. The physiological condition of the embedded bacteria was examined by
      redox activity (CTC-assay) and membrane integrity (Molecular Probes LIVE/DEAD
      Kit). Approximately 35% of the immobilised cells (Pseudomonas aeruginosa SG81)
      were damaged due to the elevated temperature required for the embedding process.
      It was shown that the surviving cells were able to multiply when provided with
      nutrients. In the case of homogeneous agarose beads, cell growth only occurred
      near the bead surface, while substrate limitation prevented growth of more deeply
      embedded cells. In the porous hydrogel, cell division was observed across the
      entire matrix due to better mass transport. It could be shown that embedding in
      the artificial gel matrix provided protection of immobilized cells against toxic
      substances such as sodium hypochlorite (0.5 mg/l, 30 min) in comparison to
      suspended cells, as observed in other immobilized systems. Thus, the model is
      suited to simulate important biofilm matrix properties.

PMID- 10968639
TI  - Isolation of Penicillium chrysogenum PEX1 and PEX6 encoding AAA proteins involved
      in peroxisome biogenesis.
AB  - In Penicillium chrysogenum, key enzymes involved in the production of penicillin
      reside in peroxisomes. As a first step to understand the role of these organelles
      in penicillin biosynthesis, we set out to isolate the genes involved in
      peroxisome biogenesis. Here we report the cloning and characterization of P.
      chrysogenum PEX1 and PEX6, which encode proteins of the AAA family of ATPases.
      The second AAA module, which is essential for the function of Pex1p and Pex6p in
      peroxisome biogenesis, is highly conserved in both PcPexlp and PcPex6p. PcPEX1
      and PcPEX6 contain three and two introns, respectively.

PMID- 10968640
TI  - Bacterial response to acetate challenge: a comparison of tolerance among species.
AB  - Although acetate formation and tolerance are important criteria for various
      aspects of biotechnological process development, available studies on acetate
      tolerance in different species are disparate. We evaluate the response of eight
      bacterial strains, including two variants of Escherichia coli, two variants of
      Staphylococcus capitis, and one each of Acetobacter aceti, Gluconobacter
      suboxydans, Lactobacillus acetotolerans, and L. bulgaricus, to acetate challenges
      under identical conditions. Our findings were: (1) wild-type organisms of species
      that are considered tolerant of acetate perform only slightly better than E. coli
      in unadapted shaker cultures; (2) the ability to tolerate acetate is strongly
      dependent on the carbon source, and is, especially for E. coli, much greater on
      glycerol than on glucose; (3) respiration is not as important to acetate
      tolerance in E. coli and S. capitis as has been reported for the acetic acid
      bacteria; (4) S. capitis was the least affected by acetate under all conditions
      and grew at up to 44 g/l acetate without any preconditioning; and (5) qualitative
      high-throughput screening of growth characteristics can be achieved with
      relatively inexpensive multiwell plate readers.

PMID- 10968641
TI  - Toluene vapour removal in a laboratory-scale biofilter.
AB  - A bench-scale biofilter with a 0.5-m high filter bed, inoculated with a toluene
      degrading strain of Acinetobacter sp. NCIMB 9689, was used to study toluene
      removal from a synthetic waste air stream. Different sets of continuous tests
      were conducted at influent toluene concentrations ranging over 0.1-4.0 g m(-3)
      and at superficial gas velocities ranging over 17.8-255 m h(-1). The maximum
      volumetric toluene removal rate for the biofilter (242 g m(-3) h(-1)) was
      obtained at a superficial gas velocity of 127.5 m h(-1) (corresponding to a
      residence time of 28 s) and a toluene inlet concentration of 4.0 g m(-3). Under
      these operating conditions, toluene removal efficiency was only 0.238, which
      suggested that effective operation required higher residence times. Removal
      efficiencies higher than 0.9 were achieved at organic loads less than 113.7 g m(
      3) h(-1). A macro-kinetic study, performed using concentration profiles along the
      bioreactor, revealed this process was limited by diffusion at organic loads less
      than 100 g m(-3) h(-1) and by biological reaction beyond this threshold.

PMID- 10968642
TI  - Estimating the availability of polycyclic aromatic hydrocarbons for
      bioremediation of creosote contaminated soils.
AB  - Bioremediation of soil contaminated by organic compounds can remove the
      contaminants to a large extent, but residual contamination levels may remain
      which are not or only slowly biodegraded. Residual levels often exceed existing
      clean-up guidelines and thereby limit the use of bioremediation in site clean-up.
      A method for estimating the expected residual levels would be a useful tool in
      the assessment of the feasibility of bioremediation. In this study, three soil
      types from a creosote-contaminated field site, which had been subjected to 6
      months of bioremediation in laboratory column studies, were used to characterize
      the residual contamination levels and assess their availability for
      biodegradation. The soils covered a wide range of organic carbon levels and
      particle size distributions. Results from the biodegradation studies were
      compared with desorption rate measurements and selective extractability using
      butanol. Residual levels of polycyclic aromatic hydrocarbons after bioremediation
      were found to be strongly dependent on soil type. The presence of both soil
      organic matter and asphaltic compounds in the soil was found to be associated
      with higher residual levels. Good agreement was found between the biodegradable
      fraction and the rapidly desorbable fraction in two of the three soils studied.
      Butanol extraction was found to be a useful method for roughly estimating the
      biodegradable fraction in the soil samples. The results indicate that both
      desorption and selective extraction measurements could aid the assessment of the
      feasibility for bioremediation and identifying acceptable end-points.

PMID- 10968643
TI  - Factors influencing the biosorption of gadolinium by micro-organisms and its
      mobilisation from sand.
AB  - The present work was devoted to the study of the biosorption capacities of
      various microbial species (Bacillus subtilis, Pseudomonas aeruginosa, Ralstonia
      metallidurans CH34 previously Alcaligenes eutrophus CH34, Mycobacterium
      smegmatis, Saccharomyces cerevisiae) for ions of the lanthanide gadolinium
      (Gd3+). The uptake by sand of this element was also measured. Saturation curves
      and Scatchard models were established for all biosorbants used in this work. The
      results enabled us to determine the binding affinities and the maximum capacities
      for biosorption of Gd3+, which ranged from 350 micromol g(-1) for B. subtilis to
      5.1 micromol g(-1) for S. cerevisiae. This study demonstrated the usefulness of
      optimisation of experimental conditions in biosorption investigations.
      Experimental results showed that biosorption could be influenced by the growth
      stage and by the composition of the growth medium of microbial cells. Finally,
      particular attention was given to the transfer of gadolinium ions from a loaded
      sand to a bacterial suspension.

PMID- 10968644
TI  - Biodegradation of azo dyes in a sequential anaerobic-aerobic system.
AB  - A sequential anaerobic aerobic treatment process based on mixed culture of
      bacteria isolated from textile dye effluent-contaminated soil was used to degrade
      sulfonated azo dyes Orange G (OG), Amido black 10B (AB), Direct red 4BS (DR) and
      Congo red (CR). Under anaerobic conditions in a fixed-bed column using glucose as
      co-substrate, the azo dyes were reduced and amines were released by the bacterial
      biomass. The amines were completely mineralized in a subsequent aerobic treatment
      using the same isolates. The maximum degradation rate observed in the treatment
      system for OG was 60.9 mg/l per day (16.99 mg/g glucose utilized), for AB 571.3
      mg/l per day (14.46 mg/g glucose utilized), for DR 112.5 mg/l per day (32.02 mg/g
      glucose utilized) and for CR 134.9 mg/l per day (38.9 mg/g glucose utilized).

PMID- 10968645
TI  - Regulation of glial cell line-derived neurotrophic factor expression by
      electroacupuncture after transient focal cerebral ischemia.
AB  - The present study was designed to investigate whether electroacupuncture (EA) is
      able to regulate glial cell line-derived neurotrophic factor (GDNF) expression
      following transient middle cerebral artery occlusion (MCAO) using reverse
      transcriptase polymerase chain reaction and immunohistochemistry in rats. The
      results indicate that after 2 h MCAO, GDNF mRNA and immunoreactivity profoundly
      increased in peri-infarct cerebral cortex, with peaks at 2 h after reperfusion,
      then declined dramatically at 12 and 24 h after reperfusion. Although EA given
      immediatelly after MCAO couldn't elevate the peaks of GDNF expression, it
      obviously raised the GDNF mRNA and immunoreactivity levels at 12 h after
      reperfusion, delayed the declining trends of GDNF mRNA and immunoreactivity
      levels. These results suggest that EA could upregulate GDNF expression after
      ischemic insult, elongating the duration of upregulated GDNF expression. This may
      be one of the mechanisms of EA anti-ischemic injury by augmenting endogenous
      protective mechanism.

PMID- 10968646
TI  - Experimental study on the low-intensity millimeter-wave electro-magnetic
      stimulation of acupuncture points.
AB  - The aim of this study was to investigate the effects of the millimeter-wave
      bioresonance therapy on acute inflammation and stressful conditions in
      experimental models. Licking reaction in mice as a component of the
      hypersensitive state evoked by subcutaneous formalin (0.03 ml of 1% solution)
      injection into the right hind paw was monitored. Different parameters of electro
      magnetic stimulation (frequencies 43 GHz and 61 GHz, intensities from 0.1 to 7
      mW/cm2, the exposure time for 3 min. or 10 min.) applied to ipsilateral acupoint
      St.36 were studied. It was found that the millimeter-wave bioresonance therapy
      improved the condition of experimental animals, accompanying by diminution of
      licking reaction which was registered for every 10 min. during 2 hours after the
      formalin test start. Effect of 10 min. irradiation was more demonstrative than 3
      min. (frequency 61 GHz, intensity 0.1 mW/cm2). Stimulation with frequency of 61
      GHz suppressed licking reaction more deeply than 43 GHz under equal intensities.
      Most beneficial effects have been observed when minimal (0.1 mW/cm2) intensity of
      electromagnetic stimulation was used.

PMID- 10968647
TI  - Electro-acupuncture attenuates nitric oxide release from rat striatum after
      transient middle cerebral artery occlusion.
AB  - Nitric oxide (NO) is an important diffusible neurotransmitter, which also has
      neurotoxicity when it is overproduced. To investigate whether electro-acupuncture
      (EA) could inhibit the excessive NO release during cerebral ischemia, we detected
      NO directly by our self-made NO sensitive electrode. The electrode was placed
      into rat striatum after transient middle cerebral artery occlusion. NO level was
      significantly increased upon the onset of ischemia and reperfusion. EA apparently
      antagonized the ischemia-elicited rise of NO, although it could not suppress the
      NO level to baseline. The results indicated that EA might inhibit directly the
      elevation of NO following cerebral ischemia.

PMID- 10968648
TI  - Analgesic effects of acupuncture on pain after mandibular wisdom tooth
      extraction.
AB  - We evaluated the analgesic effects of acupuncture on postoperative pain by
      comparing patients who underwent routine tooth extraction alone (control group)
      and those who underwent tooth extraction in combination with acupuncture
      (experimental group) by the random allocation method. As teeth easy to extract.
      requiring no gingival incision (grade A) or those difficult to extract, requiring
      gingival incision or bone cutting (grade B). As local anesthesia, 1.8 ml or 3.6
      ml of 2% xylocaine was used. The LI.4, Hegu on both sides and ST.7, Xiaguan and
      ST.6, Jiache on the affected side were selected. Low frequency electrical
      acupuncture was performed. When acupuncture was used in combination with tooth
      extraction, 3 of 22 patients did not develop postoperative pain. In patients with
      wisdom teeth difficult to extract (grade B), acupuncture used in combination with
      local anesthesia decreased postoperative pain.

PMID- 10968649
TI  - Genetic control of acute ethanol-induced behaviors in Drosophila.
AB  - BACKGROUND: In most organisms in which acute ethanol exposure has been studied,
      it leads to similar changes in behavior. Generally, low ethanol doses activate
      the central nervous system, whereas high doses are sedative. Sensitivity to the
      acute intoxicating effects of ethanol is in part under genetic control in rodents
      and humans, and reduced sensitivity in humans predicts the development of
      alcoholism (Crabbe et al., 1994; Schuckit, 1994). We have established Drosophila
      melanogaster as a model organism to study the mechanisms that regulate acute
      sensitivity to ethanol. METHODS: We measured the effects of ethanol vapor on
      Drosophila locomotor behaviors by using three different assays. Horizontal
      locomotion was quantified in a locomotor chamber, turning behavior was assayed in
      narrow tubes, and ethanol-induced loss of postural control was measured in an
      inebriometer. Mutants with altered sensitivity to the acute effects of ethanol
      were generated by treatment with ethyl methane sulfonate and isolated by
      selection in the inebriometer. We ascertained the effects of these mutations on
      ethanol pharmacokinetics by measuring ethanol levels in extracts of flies at
      various times during and after ethanol exposure. RESULTS: Among nearly 30,000
      potentially mutant flies tested, we isolated 19 mutant strains with reduced and 4
      strains with increased sensitivity to the acute effects of ethanol as measured in
      the inebriometer. Of these mutants, four showed changes in ethanol absorption.
      Two mutants, named barfly and tipsy to reflect their reduced and increased
      ethanol sensitivity in the inebriometer, respectively, were analyzed for
      locomotor behaviors. Both mutants exhibited ethanol-induced hyperactivity that
      was indistinguishable from wild type. However, barfly and tipsy displayed reduced
      and increased sensitivity to the sedative effects of ethanol, respectively.
      Finally, both mutants showed an increased rate of ethanol-induced turning
      behavior. CONCLUSIONS: The effects of acute ethanol exposure on Drosophila
      locomotor behaviors are remarkably similar to those described for mammals. The
      analysis of mutants with altered sensitivity to ethanol revealed that the genetic
      pathways which regulate these responses are complex and that single genes can
      affect hyperactivity, turning, and sedation independently.

PMID- 10968650
TI  - Chronic ethanol administration alters immunoreactivity for GABA(A) receptor
      subunits in rat cortex in a region-specific manner.
AB  - BACKGROUND: Chronic ethanol administration has a plethora of physiological
      effects. Among the most consistently observed findings is a change in the
      expression pattern of gamma-aminobutyric acid type A (GABA(A)) receptor subunits
      in the rat brain cortex. These findings led to the hypothesis of "subunit
      substitution" to account for changes in receptor function without changes in
      receptor number. METHODS: We used subunit (alpha1 and alpha4) specific antibodies
      and a combination of immunohistochemistry and immunoblotting to examine
      subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for
      their response to 2 weeks of forced ethanol administration. RESULTS: Overall,
      cortical immunoreactivity for the alpha1 subunit was decreased and for the alpha4
      subunit increased whether measured immunohistochemically or by immunoblotting.
      Piriform cortex exhibited a bidirectional change in GABA(A) receptor alpha1 and
      alpha4 immunoreactivity, similar to that previously observed in preparations of
      whole cortex. However, in parietal cortex, declines in alpha1 immunoreactivity
      (55 +/- 12% control value [CV] and 88.3 +/- 4.3% CV; immunohistochemistry and
      immunoblotting, respectively) were not accompanied by concomitant increases in
      alpha4 immunoreactivity (104 +/- 8% CV and 116 +/- 9.3% CV; immunohistochemistry
      and immunoblotting, respectively). Conversely, alpha4 immunoreactivity increased
      in cingulate cortex (210 +/- 30% CV and 134 +/- 9.5% CV; immunohistochemistry and
      immunoblotting, respectively) without a decline in alpha1 immunoreactivity (90 +/
      4% CV and 91.3 +/- 3.9% CV; immunohistochemistry and immunoblotting,
      respectively). Prefrontal and motor cortex exhibited GABA(A) receptor subunit
      peptide alterations, but these changes varied with the method of analysis.
      CONCLUSIONS: These findings demonstrate that ethanol dependence results in
      nonuniform changes in GABA(A) receptor subunit peptide levels across the rat
      brain cortex and suggest that mechanisms which subserve functional changes in
      receptor activity may vary in accordance with anatomic or cellular differences
      within the cortex.

PMID- 10968651
TI  - Changes in activity and regulation of the cardiac Ca2+ channel (L-type) by
      protein kinase C in chronic alcohol-exposed rats.
AB  - BACKGROUND: It has been reported recently that long-term alcohol exposure in rats
      increases the number of dihydropyridine binding sites in cardiac membrane
      preparations. We fed Sprague Dawley rats a liquid diet that contained ethanol as
      36% of total calories for 4 to 6 months and studied how alcohol exposure affected
      the activity and regulation of the cardiac Ca2+ channel. METHODS: Dihydropyridine
      sensitive cardiac Ca2+ channel activity was measured as the rate of Mn2+ quench
      of the cytosolic fura-2 signal in electrically stimulated myocytes. RESULTS: In
      control rat myocytes, pretreatment with phorbol 12-myristate 13-acetate (PMA), an
      activator of protein kinase C (PKC), reduced the rate of Mn2+ quench to 68% of
      the untreated cell response. Pretreatment with GF109203X, a protein kinase C
      inhibitor, enhanced the rate of influx by 56%, whereas Go6976, an inhibitor of
      PKC alpha, beta, and gamma, did not affect the rate of influx. By contrast, PMA
      did not affect the rate of Mn2+ quench in alcoholic myocytes; however, the PKC
      inhibitor GF109203X still enhanced the rate of Mn2+ quench by 33%. Similar to
      control myocytes, no effect was observed after pretreatment with Go6976 in the
      alcoholic cells. In both Western blot and immunoprecipitation experiments, PKC
      epsilon expression in alcohol-exposed myocytes was reduced to 68% of the control.
      However, the ratio of membrane/ cytosolic distribution of PKC epsilon in
      alcoholic myocytes was increased from 1.6 to 2.6. No change was detected in the
      expression of PKC alpha and PKC delta. PKC activity, measured in the presence of
      Go6976, which inhibits PKC alpha, beta, and gamma, was reduced in alcoholic
      myocytes to 57% of the control, but the proportion of PKC activity in the
      particulate fraction was increased from 26% in the control myocytes to 36% in the
      alcoholic myocytes. CONCLUSIONS: Altered expression and activity of PKC may be
      associated with changes in the regulation of the cardiac Ca2+ channel found in
      the hearts of rats chronically exposed to alcohol. Specifically, we found that
      the novel class of PKC isozymes is responsible for regulating the cardiac Ca2+
      channel in control cardiomyocytes, and that the loss of PMA modulation found in
      the alcoholic cells may be due, in part, to reduced expression and altered
      distribution of PKC epsilon.

PMID- 10968652
TI  - The development of an ethanol model using social insects I: behavior studies of
      the honey bee (Apis mellifera L.).
AB  - BACKGROUND: The purpose of this experiment was to test the feasibility of
      creating an animal model of ethanol consumption using social insects. Honey bees
      were selected as the model social insect because much is known about their
      natural history, physiology, genetics, and behavior. They are also inexpensive to
      procure and maintain. Of special interest is their use of communication and
      social organization. METHODS: Using both between- and within-experiment designs,
      studies were conducted with harnessed foragers to determine whether honey bees
      would consume ethanol mixed with sucrose (and, in some cases, water). Shuttle-box
      and running-wheel studies were conducted to examine the effect of ethanol on
      locomotion. The effect of ethanol on stinging behavior in harnessed foragers was
      investigated. The effect of ethanol on Pavlovian conditioning of proboscis
      extension was also investigated. Finally, in a self-administration study,
      foraging honey bees were trained to fly to an artificial flower containing
      ethanol. RESULTS: (1) Harnessed honey bees readily consume 1%, 5%, 10%, and 20%
      ethanol solutions; (2) 95% ethanol will also be consumed as long as the antennae
      do not make contact with the solution; (3) with the exception of 95% ethanol,
      consumption as measured by contact time or amount consumed does not differ in
      animals that consume 1%, 5%, 10%, and 20% ethanol solutions; (4) exposure to a
      lesser (or greater) concentration of ethanol does not influence consumption of a
      greater (or lesser) concentration; (5) consumption of 10% and 20% ethanol
      solutions decreases locomotion when tested in both a shuttle-box and running
      wheel situation; (6) consumption of 1%, 5%, 10%, and 20% ethanol does not
      influence stinging behavior in harnessed foragers; (7) ethanol solutions greater
      than 5% significantly impair Pavlovian conditioning of proboscis extension; and
      (8) free-flying honey bee foragers will readily drink from an artificial flower
      containing 5% ethanol. CONCLUSIONS: The experiments on consumption, locomotion,
      and learning suggest that exposure to ethanol influences behavior of honey bees
      similar to that observed in experiments with analogous vertebrates. The honey bee
      model presents unique research opportunities regarding the influence of ethanol
      in the areas of language, social interaction, development, and learning. Although
      the behavioral results are interesting, similarity between the physiologic
      effects of ethanol on honey bees and vertebrates has not yet been determined.

PMID- 10968653
TI  - Children's hedonic response to the smell of alcohol: effects of parental drinking
      habits.
AB  - BACKGROUND: Previous research in our laboratory revealed that during the first
      year of life, infants who had more exposure to alcohol, as inferred from
      questionnaires about parental alcoholism and alcohol intake, mouthed an ethanol
      scented toy more compared with less exposed infants. The present study focused on
      older children (3.8-6.0 years) to determine whether their hedonic response to the
      odor of alcohol was related to the drinking habits of their parents. METHODS: Age
      appropriate, game-like tasks that were fun for children and minimized the impact
      of language development were used to examine their preferences and identification
      of a variety of odors, one of which was beer. RESULTS: The children's preference
      for the odor of beer varied as a function of the escape drinking of their mothers
      alone or both parents. That is, children who lived in a household in which one or
      both parents drank alcohol to escape were significantly more likely to dislike
      the odor bottle that contained alcohol when compared with children whose parents
      did not drink to escape. This difference between the groups was odor specific.
      Additional analyses also revealed that the fathers of children who rejected the
      beer odor reported drinking significantly more than the fathers of those who
      liked the odor. CONCLUSIONS: These findings suggest that some early learning
      about alcohol is based on sensory experiences and anchor it to children's
      experiences at home and the emotional context in which their parents experience
      alcohol.

PMID- 10968654
TI  - Ethanol reinforcement in nondeprived mice: effects of abstinence and naltrexone.
AB  - BACKGROUND: Operant experiments which indicate that ethanol can serve as a
      reinforcer to maintain lever responding during limited periods of access have not
      been conducted on non-food-deprived mice, as they have for rats and monkeys.
      Furthermore, there are no reports of the effects of chronic ethanol and
      subsequent abstinence on ethanol reward in mice. Finally, although naltrexone
      reduces responding for ethanol in food-deprived mice, the effects of the drug on
      ethanol reward for non-food-deprived mice have not been reported. METHODS: In
      three experiments, lever responding for ethanol (10-12%) was established in
      C57BL/6 (B6) mice by using either sucrose or saccharin fading procedures commonly
      used for rats. Experiment 1 examined both appetitive and consummatory responses
      while sucrose was faded from the ethanol solutions. Experiment 2 examined lever
      responding and ethanol intake (1) during saccharin fading; (2) when reinforcement
      schedules, reward availability, and primary conditioned reinforcers were
      manipulated; and (3) when mice were allowed chronic ethanol consumption followed
      by forced abstinence. Experiment 3 examined the effects of low doses of
      naltrexone on ethanol reward. RESULTS: Lever responding for ethanol can be
      established in non-food-deprived mice with the sucrose and saccharin fading
      procedures commonly used for rats. Lever responses increased with decreases in
      the reinforcer and increases in schedule demand, which indicated the reward value
      of the ethanol solution. Removal of ethanol from the solution reduced consumption
      with no change in the appetitive, instrumental response, which indicated that the
      two responses were under control of different stimuli, perhaps mediated by
      different neural mechanisms. Forced abstinence after chronic ethanol exposure
      increased responding for the drug, which suggested increased reward value.
      Naltrexone reduced responding as previously reported for food-deprived B6 mice.
      CONCLUSIONS: Ethanol appears to serve as a reinforcer for non-food-deprived or
      non-water-deprived B6 mice. Its reinforcing effects are increased by forced
      abstinence after chronic exposure and are decreased by naltrexone.

PMID- 10968655
TI  - Inferior colliculus intracellular response abnormalities in vitro associated with
      susceptibility to ethanol withdrawal seizures.
AB  - During ethanol withdrawal (ETX), rats become susceptible to audiogenic seizures
      in which the inferior colliculus (IC) is known to play a critical role. The
      present study examined changes in membrane properties that occurred in IC dorsal
      cortex (ICd) neurons in brain slices from rats after 4 days of three times daily
      intragastric ethanol, which is proposed to be an analog of binge drinking.
      Compared with neurons from control animals, ICd neurons during ETX had action
      potentials (APs) with lower thresholds, a greater incidence of spontaneous APs, a
      reduced degree of spike firing adaptation, and an increased incidence of anode
      break firing. With synaptic stimulation, epileptiform firing was seen in nearly
      50% of ICd neurons during ETX but never was seen in normal ICd neurons except
      after perfusion of the gamma-aminobutyric acid type A (GABA(A)) antagonist
      bicuculline. Paired pulse responses of ICd neurons were also abnormal during ETX.
      Thus, in 75% of normal rats, paired synaptic stimuli inhibited the second
      response, but during ETX all neurons tested showed paired pulse facilitation.
      These aberrant membrane and synaptic properties provide direct evidence for the
      hyperexcitability of IC neurons during ETX. They may be due, in part, to changes
      in GABAergic and glutamatergic neurotransmission known to be produced during
      withdrawal after continued ethanol administration.

PMID- 10968656
TI  - The influence of maternal drinking and drug use on the quality of the home
      environment of school-aged children.
AB  - BACKGROUND: Although many studies have examined the development of children of
      male alcoholics, few studies have considered substance use by the female
      caregiver. This study evaluated the relationship between substance use by female
      caregivers and factors that affect the child-rearing environment. METHODS: A
      total of 480 inner-city African-American women were recruited during pregnancy
      for a longitudinal study of the effects of prenatal alcohol use and substance use
      by caregivers on the development of their children. All women were screened for
      alcohol consumption at their first prenatal visit to a large urban maternity
      hospital. Those who averaged seven or more drinks per week (0.5 oz absolute
      alcohol per day) at the time of conception were invited to participate in the
      study, as was a 5% random sample of lighter drinkers and abstainers. At the 7.5
      year follow-up assessment, the quantity and frequency of alcohol consumption and
      drug use, as well as several measures of the child-rearing environment, were
      assessed for 231 of the caregivers. RESULTS: Current alcohol use was uncorrelated
      with standard demographic factors, such as socioeconomic status, but was related
      to poorer family functioning, lower quality of parental intellectual stimulation,
      and higher levels of domestic violence. There were independent effects of illicit
      drug use on family environment, domestic violence, and caregiver depression.
      History of drinking during pregnancy, however, was not related to the current
      child-rearing environment. Poorer parental functioning generally was found only
      among the caregivers who currently drank both heavily (six or more
      drinks/occasion) and frequently (three or more days/week). After controlling for
      lifetime alcohol problems, current drinking still predicted a less cohesive and
      organized family environment and higher levels of domestic violence. CONCLUSIONS:
      Current heavy, frequent drinking in this relatively homogenous, economically
      disadvantaged sample was unrelated to demographics and seemed to have an
      important negative impact on the quality of the child-rearing environment,
      whereas drinking during pregnancy was unrelated to the current child-rearing
      environment.

PMID- 10968657
TI  - Use of a high-risk alcohol relapse scale in evaluating liver transplant
      candidates.
AB  - BACKGROUND: Methods to improve assessment, selection, and monitoring of patients
      with alcoholic cirrhosis who pursue liver transplantation are sought
      continuously. We chose to investigate the use of the High-Risk Alcohol Relapse
      (HRAR) scale in our transplant population in the hope that it would improve our
      ability to identify and follow patients at highest risk for alcohol relapse.
      METHODS: Detailed alcohol histories of 207 patients evaluated for liver
      transplantation were collected and graded for severity by using the HRAR. The
      HRAR provides information on the duration of alcohol use (a measure of
      chronicity), daily quantity of alcohol use, and rehabilitation experiences
      (treatment responsiveness). Posttransplant alcohol use was monitored through
      clinical follow-up in the transplant clinic. RESULTS: Although men and women had
      similar years of heavy drinking pretransplant, women's daily alcohol consumption
      was significantly less than men's. HRAR scores did not distinguish those listed
      for transplant from those not listed or those who drank posttransplant from those
      who did not. Transplant patients were predominantly in the low-risk group (83%
      had an HRAR score <4). CONCLUSIONS: The HRAR did not have predictive ability in
      our transplant population. Few of our patients were rated as high risk, and few
      drank posttransplant. Nevertheless, identifying patients at high risk may improve
      clinical care and decrease the rate of posttransplant alcohol consumption.

PMID- 10968658
TI  - Enhanced clinical utility of gamma-CDT in a general population.
AB  - BACKGROUND: The use of a combination of markers to detect excessive alcohol
      consumption has been reported to provide better sensitivity in the diagnosis of
      alcohol abuse than single markers. However, the optimal combination of markers
      for the diagnosis of alcohol abuse has not yet been found. The aim of this study
      was to compare the diagnostic value of carbohydrate-deficient transferrin (CDT)
      and gamma-glutamyltransferase (GGT) to discriminate among heavy drinkers (>280
      g/week), moderate drinkers (105-280 g/week), and light drinkers (<105 g/week).
      Their mathematical combination, named gamma-CDT, which has been found to be a
      strong marker of alcohol abuse in a former study, was also evaluated. METHODS:
      The study was conducted in a group of 6962 subjects (3974 males and 2988
      females), between the ages of 25 and 74 years, who participated in a large cross
      sectional risk factor survey carried out in five geographic areas in Finland. In
      each study area, an age- and gender-stratified random sample was drawn from the
      general population. Sensitivity, specificity, positive and negative predictive
      values, and receiver operating characteristic curves were used to evaluate the
      performance of CDT, GGT, and gamma-CDT. RESULTS: For both sexes, the combined
      marker had the highest specificity (95%) and sensitivity in detecting heavy
      drinkers. In all cases, gamma-CDT had the highest area under ROC plots. Our
      results also showed that GGT and CDT have similar, and rather low, sensitivity
      but high specificity in a general population. CONCLUSIONS: Compared with single
      markers, a significant improvement of sensitivity was obtained when the
      combination of both markers was used, especially in females.

PMID- 10968659
TI  - Adverse working conditions and alcohol use in men and women.
AB  - OBJECTIVE: This study examined the association between adverse working conditions
      and abstinence and heavy drinking. METHODS: The study was a cross-sectional study
      within the framework of a general population survey conducted in Eindhoven, The
      Netherlands (N = 7533). Working conditions were classified into four domains:
      hazardous physical working conditions, demands at work, level of control over
      one's job, and support from coworkers and supervisors. Abstainers were compared
      with drinkers; within drinkers, heavy drinkers were compared with light-moderate
      drinkers, and those who reported binge drinking were compared with those who did
      not report binge drinking. RESULTS: Respondents who reported adverse working
      conditions were as likely to be abstainers as they were to be drinkers. Within
      drinkers, males and females who reported high hazardous physical working
      conditions were more likely to be heavy drinkers than to be light-moderate
      drinkers (light-moderate is not just an amount, but a combination of amount and
      frequency) and to report binge drinking (males only). Respondents who reported
      high demands were also more likely to be heavy drinkers than to be light-moderate
      drinkers. CONCLUSIONS: Stressful circumstances, such as adverse working
      conditions, were associated with high levels of alcohol intake among drinking men
      and women.

PMID- 10968660
TI  - In vivo detection and functional correlates of white matter microstructural
      disruption in chronic alcoholism.
AB  - BACKGROUND: Postmortem studies report degradation of brain white matter
      microstructure in chronic alcoholism, but until recently, in vivo neuroimaging
      could provide measurement only at a macrostructural level. The development of
      magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a
      method for depicting and quantifying the diffusion properties of white matter
      expressed as intravoxel and intervoxel coherence of tracts and fibers. METHODS:
      This study used DTI to examine the intravoxel coherence measured as fractional
      anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu
      and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified
      alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational
      analyses examined the relationships between regional DTI measures and tests of
      attention and working memory in the alcoholic patients. RESULTS: The alcoholic
      group had lower regional FA than the control group. C was lower in the alcoholics
      than controls in the splenium only. Working memory correlated positively with
      splenium FA, whereas attention correlated positively with genu C. CONCLUSIONS:
      These results provide in vivo evidence for disruption of white matter
      microstructure in alcoholism and suggest that interruption of white matter fiber
      coherence contributes to disturbance in attention and working memory in chronic
      alcoholism.

PMID- 10968661
TI  - Increased serum tissue polypeptide specific antigen (TPS) in alcoholics: a
      possible marker of alcoholic hepatitis.
AB  - BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is widely used as a
      tumor proliferation marker. There is some evidence of an increase in serum TPS in
      benign liver diseases. The aim of the study was to evaluate serum TPS levels in
      alcoholics. METHODS: Seventy-seven alcoholics (64 men and 13 women) admitted to
      the hospital with ethanol withdrawal syndrome entered the study. Twenty-three
      patients were biopsied (12 of them had alcoholic hepatitis and 11 steatosis or
      fibrosteatosis). Serum TPS was determined by enzyme immunoassay in all cases.
      Results were compared with those of 24 healthy controls. RESULTS: Serum TPS
      levels were significantly increased in alcoholic patients compared with controls
      (median 365 units/liter and range 41-6400 units/liter versus median 79
      units/liter and range 19-235 units/ liter, respectively, p < 0.0001). Seventeen
      alcoholics (22%) had a TPS value 10 times higher than the upper normal threshold
      level (> or = 1000 units/liter). Among alcoholics, serum TPS levels were higher
      in patients with alcoholic hepatitis than in those with steatosis or
      fibrosteatosis (median 1486 units/liter and range 176-5023 units/liter versus
      median 106 units/liter and range 41-221 units/liter, respectively, p = 0.0001),
      offering a better discriminant value for the diagnosis of alcoholic hepatitis
      than usual liver function parameters. Serum TPS values showed significant
      correlation with liver cell necrosis and Mallory's hyaline degeneration. TPS
      values decreased after alcohol abstinence during hospital admission. CONCLUSIONS:
      Serum TPS is frequently increased in alcoholics and may be a marker of alcoholic
      hepatitis. Specificity of this molecule as a tumor marker is limited in
      alcoholics.

PMID- 10968662
TI  - Ethanol in human brain by magnetic resonance spectroscopy: correlation with blood
      and breath levels, relaxation, and magnetization transfer.
AB  - BACKGROUND: Proton magnetic resonance spectroscopy (1H MRS) allows measurement of
      alcohol in the human brain after alcohol consumption. However, the quantity of
      alcohol that can be detected in the brain by 1H MRS pulse sequences has been
      controversial, with values ranging from about 24% to 94% of the temporally
      concordant blood alcohol concentrations. The quantitation of brain alcohol is
      critically affected by the kinetics of alcohol uptake and elimination, by the
      relaxation times of the protons that give rise to the brain alcohol signal, and
      by the specifics of both pulse sequence timing and radio frequency pulse
      applications. METHODS: We investigated these factors in 20 light-drinking
      subjects after oral administration of approximately 0.85 g/kg body weight of
      alcohol by localized 1H MRS and measurements of blood and breath alcohol
      concentrations obtained at the same time. Specifically, we measured transverse
      and longitudinal relaxation times of brain alcohol and its signal saturation on
      application of on- or off-resonance radio frequency pulses. All 1H MRS
      measurements were performed at a time after brain and blood alcohol
      concentrations had equilibrated. RESULTS: 1H MRS measures of brain alcohol were
      correlated highly with both breath and blood alcohol concentrations after
      equilibration in brain tissue. The measured 1H MRS relaxation times of brain
      alcohol were shorter than given in previous reports that were limited by smaller
      subject numbers, improper use of 1H MRS methods, and estimates rather than
      measurements. The brain alcohol signal decreased by about 30% on application of
      on- or off-resonance saturation pulses. CONCLUSIONS: 1H MRS allows direct
      measurement of brain alcohol, formerly only possible indirectly through
      inferences from breath alcohol levels. Quantitation of brain alcohol levels need
      to take into account measured relaxation times and alcohol signal attenuation due
      to presence and timing of standard radio frequency MRS pulses. Saturation
      experiments give evidence for the existence of more than one compartment of brain
      alcohol characterized by different molecular environments. They suggest that a
      fraction of brain alcohol is invisible to 1H MRS.

PMID- 10968663
TI  - Ethanol decreases zinc transfer to the fetus in normal but not metallothionein
      null mice.
AB  - BACKGROUND: Ethanol causes significant teratogenicity in normal (MT+/+) but not
      metallothionein-null (MT-/-) fetuses. Impaired maternal fetal zinc (Zn) transfer
      is indicated, because ethanol significantly reduces plasma Zn concentrations in
      MT+/+ dams while increasing concentrations in MT-/- dams. In this study we
      examined maternal-fetal Zn homeostasis in response to ethanol in MT+/+ and MT-/-
      mice and the origins of the increase in plasma Zn in MT-/- mice. METHODS AND
      RESULTS: Mice were treated with saline or ethanol (0.015 ml/g intraperitoneally
      at 0 and 4 hr) on day 12 of gestation. An additional subcutaneous injection of
      65Zn tracer was administered after the second ethanol injection before mice were
      killed 3 hr later. Maternal liver MT levels were not different between ethanol
      and saline MT+/+ mice. Both liver Zn and 65Zn levels were higher in MT+/+ mice.
      Plasma Zn concentrations were higher in MT-/- mice, with MT-/- ethanol-treated
      mice having levels greater than those of MT-/- saline-treated controls. MT+/+
      ethanol-treated fetuses exhibited lower 65Zn transfer and whole Zn concentrations
      compared with MT+/+ and MT-/- saline and MT-/- ethanol fetuses. So we could
      examine changes in plasma Zn after ethanol treatment, MT+/+ and MT-/- mice were
      injected with 65Zn 3 days before they received ethanol treatment. Muscle and skin
      showed a decrease in 65Zn retention in both genotypes over 3 hr. There was a
      trend toward greater 65Zn release from skin and muscle at an earlier time in MT-/
      mice: 24% vs. 2% decrease (MT-/- vs. MT+/+) for muscle and 28% vs. 15% decrease
      (MT-/- vs. MT+/+) for skin at 2 hr. CONCLUSIONS: The results show (a) that
      ethanol interferes with the transfer of Zn to the fetus, and that this is MT
      dependent, and (b) that the increase in plasma Zn seen in MT-/- mice after
      ethanol administration is a result of Zn release from the skin and muscle, in the
      absence of hepatic Zn sequestration.

PMID- 10968664
TI  - Understanding drinking during pregnancy among urban American Indians and African
      Americans: health messages, risk beliefs, and how we measure consumption.
AB  - BACKGROUND: Little is known about urban American Indian and African American
      women's drinking during pregnancy, or their beliefs about the risk of doing so.
      However, rates of fetal alcohol syndrome (FAS) are believed to be highest among
      those ethnic groups. METHODS: The Developing Effective Educational Resources
      (DEER) project recruited pregnant American Indian, African American, and white
      women from urban California areas (n = 321), to develop culturally appropriate
      consumption measures, to gather epidemiological data about drinking during
      pregnancy, and to assess exposure and reactions to health warnings intended to
      encourage abstinence during pregnancy. RESULTS: The study found high levels of
      exposure to health warnings among all ethnic groups, but many women were unclear
      about the actual consequences of FAS, about the risk of drinking even beer or
      wine or wine coolers, or about the value of reducing intake at any time during
      pregnancy. The majority of the women who drank malt liquor, fortified wine, wine,
      and spirits reported having larger than standard drinks, and daily drinkers had
      the highest levels of reporting error. When drink size was considered in the
      calculation of alcohol volume, average daily volume of consumption during
      pregnancy increased to the FAS risk level (average daily volume > or = 1) in the
      overall sample and among the African American and white subjects. CONCLUSIONS:
      Because some women, especially heavy drinkers, will continue drinking despite
      exposure to abstention-oriented health messages, it may be prudent to develop
      campaigns and interventions that provide factual information to help at-risk
      women reduce their drinking during pregnancy. Women could be advised of beverage
      equivalency, of standard drink sizes, and of how their own drinks compare with
      standard ones. Reliance on standard drink sizes in research can result in
      significant underreporting of consumption, especially among pregnant risk
      drinkers.

PMID- 10968665
TI  - Binge pattern ethanol exposure in adolescent and adult rats: differential impact
      on subsequent responsiveness to ethanol.
AB  - BACKGROUND: Recent evidence indicates that adolescent animals are more sensitive
      than adults to the disruptive effects of acute ethanol exposure on spatial
      learning. It is not yet known whether adolescent animals are also more sensitive
      than adults to the enduring neurobehavioral effects of repeated ethanol exposure.
      In this study, animals were exposed to ethanol in a binge-pattern during either
      adolescence or adulthood. At a time when all subjects were adults, spatial
      working memory was examined in the absence and presence of an acute ethanol
      challenge. METHODS: Rats were exposed to ethanol (5.0 g/kg intraperitoneally) or
      isovolumetric saline at 48 hr intervals over 20 days. Exposure began on either
      postnatal day 30 (adolescent group) or 70 (adult group). Twenty days after the
      final injection, a time at which all animals were adults, the subjects were
      tested on an elevated plus maze and then were trained to perform a spatial
      working memory task on an eight-arm radial maze. At the beginning of each session
      of training on the working memory task, subjects retrieved food rewards on four
      of the eight arms. After a delay, subjects were placed on the maze and allowed to
      retrieve food from the remaining four arms. RESULTS: Prior exposure to ethanol
      did not influence behavior on the plus maze. Performance of the groups did not
      differ during acquisition of the spatial working memory task with a 5 min delay
      or during subsequent testing with a 1 hr delay. However, animals treated with
      ethanol during adolescence exhibited larger working memory impairments during an
      ethanol challenge (1.5 g/kg intraperitoneally) than subjects in the other three
      groups. CONCLUSIONS: The findings indicate that binge pattern exposure to ethanol
      during adolescence enhances responsiveness to the memory-impairing effects of
      ethanol in adulthood.

PMID- 10968666
TI  - Treatment of older women with alcohol problems: meeting the challenge for a
      special population.
AB  - As a larger proportion of the U.S. population reaches late life, there are new
      challenges to providing quality health care services for this group. Record
      numbers of adults over 60 are seeking health care for acute and chronic
      conditions. Older women represent the largest single group of health care users
      in this country. Twelve percent of older women regularly drink in excess of
      recommended guidelines (no more than one drink per day or seven drinks per week)
      and can be considered at-risk drinkers. Problems related to alcohol use and
      misuse can seriously affect many of the health concerns common among older women,
      including chronic illnesses and depression. Older women have specific risks and
      vulnerabilities to alcohol use, which include a swifter progression to alcohol
      related illness. However, women in later life who have alcohol problems are
      underscreened and underdiagnosed, have significant barriers in accessing health
      care, and respond differentially to standard specialized treatment protocols. To
      date, research on these topics has been limited. Furthermore, there is a paucity
      of research focused on treatment outcomes for elderly adults with alcohol
      problems, with almost no emphasis on women. This paper presents the state of
      knowledge about alcohol health services for older women and provides
      recommendations for necessary future health services research on this vulnerable
      population.

PMID- 10968668
TI  - Pregnant, alcohol-abusing women.
AB  - BACKGROUND: This paper reviews the literature on the identification and treatment
      of pregnant, alcohol-abusing women, with special emphasis on poor women who have
      access to treatment through Medicaid. METHODS: The paper discusses the gaps and
      controversies in the literature and suggests five priorities for future research.
      RESULTS: Studies that attempt to identify pregnant women who drink conclude that
      heavier drinkers enter prenatal care later than other women, that many health
      care providers fail to recognize alcohol abuse by pregnant women, and that
      research on screening techniques is still in the early stages. Treatment research
      suggests that comprehensive, holistic treatment approaches, as well as brief
      interventions and case management, have been successful in reducing prenatal
      alcohol use. Debate continues over whether treatment should be voluntary.
      CONCLUSIONS: The five areas identified as priorities for future research include
      (1) developing reliable and valid measures to identify alcohol abuse in pregnant
      women, (2) creating training programs for providers, (3) generating programs to
      reduce barriers to care, (4) determining which treatment programs are most
      successful, and (5) estimating the costs and benefits of various treatment
      approaches.

PMID- 10968667
TI  - Barriers to and need for alcohol services for women in rural populations.
AB  - BACKGROUND: This article reviews and summarizes the research on alcohol problems
      and issues related to alcohol services for rural women. METHODS: We discuss the
      prevalence of alcohol problems, help-seeking behavior and barriers to help
      seeking for rural women and suggest directions for future research for rural
      women with alcohol problems. We also address key methodological issues in
      measuring rurality that must be considered when designing research on rural
      women. RESULTS: Little is known about these topics, specifically for rural women,
      and much has to be currently inferred either from studies of psychiatric
      disorders in rural populations, from studies of urban or suburban women, or from
      general research about rural life. CONCLUSIONS: Increased knowledge regarding
      specific issues for women with alcohol problems in rural areas, particularly
      about gender-specific barriers to obtaining services and gender-specific needs
      for particular services, will be beneficial for developing programs designed to
      meet the unique needs of this group of women.

PMID- 10968669
TI  - Family violence and victimization: treatment issues for women with alcohol
      problems.
AB  - A brief overview of the prevalence of violence in women's lives and psychological
      and physical consequences of these experiences is presented, with special
      attention to populations of women with alcohol and other drug problems. Barriers
      to identification of violent victimization within health care settings are
      discussed. Finally, potential areas for further consideration regarding policy,
      practice, and research are identified. The relationships between women's
      experiences of violent victimization and their use of alcohol and drugs are
      documented, although prior research has not fully explored or explained the
      etiologic nature of these relationships. Of additional importance is the
      recognition that various forms of violence occur throughout a single life span.
      Women's histories of violent victimization negatively affect their children, and
      thus, intergenerational issues are of concern. Understanding how the combined
      problems of alcohol and drugs interconnect with violence is relevant to the
      delivery of health services for women.

PMID- 10968670
TI  - Welfare reform and the changing landscape of substance abuse services for low
      income women.
AB  - Recent welfare reform policies could fundamentally change the nature of public
      sector substance abuse services available to women. This review summarizes what
      is presently known about substance abuse services and women on welfare, and
      identifies limitations in our current knowledge about the potential effects of
      welfare reform. Five crucial areas are examined in which research on services has
      fallen short: (1) assessing the need for substance abuse services across a broad
      spectrum of welfare populations, (2) exploring the role that alcohol and drug
      problems play in welfare dependency, (3) examining how welfare programs can serve
      as pathways to alcohol and drug treatment, (4) evaluating the effectiveness and
      costs of innovative welfare-treatment programs, and (5) understanding systems
      level adaptations in substance abuse services for women that result from changing
      welfare policies. We conclude that researchers who study services should take a
      broad view of these issues-one that considers the unique situation of poor women
      and single mothers, that views substance abuse within a work impairment or
      disabilities framework, and one that is attuned to future changes in the effects
      of welfare reform as the economy and labor markets undergo change.

PMID- 10968671
TI  - Alcohol and eating disorders: implications for alcohol treatment and health
      services research.
AB  - BACKGROUND: This paper focuses on the co-occurrence of alcoholism and eating
      disorders and the clinical implications for treating this comorbidity in women
      with alcohol use disorders. There is substantial literature that supports higher
      than expected rates of co-occurrence of these two disorders. In addition, there
      is evidence that the co-occurrence of alcoholism and eating disorders is more
      likely to occur in the presence of other psychiatric disorders. A critical
      analysis of the studies on the comorbidity of these disorders is conducted along
      with a review of the possible etiologic association between the two disorders.
      Crucial questions related to pharmacological and behavioral treatments for this
      subgroup of alcoholic women with eating disorders are raised from a health
      services research perspective. CONCLUSIONS: There is substantial evidence that
      alcoholism and eating disorders co-occur at high rates. However, as this review
      points out, several important research questions remain regarding both the
      clinical manifestations of each problem in women who are comorbid for both
      disorders and the treatment implications.

PMID- 10968672
TI  - Women and alcohol problems: a critical analysis of the literature and unanswered
      questions.
AB  - The evaluation of alcohol treatment services for women that emerged from the
      deliberations of the expert panel and RSA roundtable clearly documents the
      importance of interdisciplinary research. This research considers the particular
      social and physical context of women's lives and uses measurement tools and
      outcome measures appropriate for women. Development of gender-tested
      measurements, gender-relevant treatment services, and gender-appropriate outcome
      evaluations is necessary to ensure that women receive the services they need. The
      inclusion of women from geographically and ethnically diverse subject
      populations, as well as from subgroups who have traditionally been excluded from
      health research, is critical in the development of scientifically sound, research
      based knowledge of the treatment of women with alcohol problems. The papers that
      follow include critical reviews of the literature by members of the expert panel,
      and these reviews were enriched by the roundtable discussion at RSA. Schmidt and
      McCarty evaluate the research on women supported on welfare. The unique
      challenges for pregnant women on Medicaid are discussed by Hankin, McCaul, and
      Heussner. The research on alcohol treatment specific to older women is critiqued
      by Blow, and the barriers and need for alcohol service for women in rural
      populations are discussed by Booth and McLaughlin. The relationships between
      substance abuse and violence are assessed by Miller, Wilsnack, and Cunradi.
      Finally, Sinha and O'Malley discuss critical gaps in understanding the impact on
      treatment outcomes of co-occurring disorders such as depression, anxiety, and
      eating disorders.

PMID- 10968673
TI  - Methods of synthesis of glycosyl fluorides.
AB  - In recent years glycosyl fluorides have been utilized as versatile sugar donors
      in the synthesis of natural products and carbohydrates. This paper provides an
      update on the advances made in the preparation of glycosyl fluorides during the
      last decade (1988-1998).

PMID- 10968674
TI  - Glycosyl fluorides in glycosidations.
AB  - This short review deals with the recent progress in chemical O-glycosidation and
      C-glycosylation methods using glycosyl fluorides as glycosyl donors. Pyranosyl
      and furanosyl fluorides were effectively activated by fluorophilic reagents such
      as SnCl2-AgClO4, SnCl2-TrClO4, SnCl2-AgOTf, TMSOTf, SiF4, BF3 x Et2O, TiF4, SnF4,
      Cp2MCl2-AgClO4 (M = Zr or Hf), Cp2ZrCl2-AgBF4, Cp2HfCl2-AgOTf, Bu2Sn(ClO4)2,
      Me2GaCl, Tf2O, LiClO4, Yb(OTf)3, La(ClO4)3 x nH2O, La(ClO4)3 x nH2O-Sn(OTf)2, Yb
      Amberlyst 15, SO4/ZrO2, Nafion-H, montmorillonite K-10, and TrB(C6F5)4 to react
      with alcohols to give the corresponding O-glycosides in high yields. Furthermore,
      several types of C-glycosyl compounds, such as aryl, allyl and alkyl C-glycosyl
      derivatives, were also obtained by the glycosylation using glycosyl fluorides and
      the corresponding nucleophile with or without a Lewis acid.

PMID- 10968675
TI  - Glycosyl fluorides in enzymatic reactions.
AB  - Glycosyl fluorides have considerable importance as substrates and inhibitors in
      enzymatic reactions. Their good combination of stability and reactivity has
      enabled their use as glycosyl donors with a variety of carbohydrate processing
      enzymes. Moreover, the installation of fluorine elsewhere on the carbohydrate
      scaffold commonly modifies the properties of the glycosyl fluoride such that the
      resultant compounds act as slow substrates or even inhibitors of enzyme action.
      This review covers the use of glycosyl fluorides as substrates for wild-type and
      mutant glycosidases and other enzymes that catalyze glycosyl transfer. The use of
      substituted glycosyl fluorides as inhibitors of enzymes that catalyze glycosyl
      transfer and as tools for investigation of their mechanism is discussed,
      including the labeling of active site residues. Synthetic applications in which
      glycosyl fluorides are used as glycosyl donors in enzymatic transglycosylation
      reactions for the synthesis of oligo- and polysaccharides are then covered,
      including the use of mutant glycosidases, the so-called glycosynthases, which are
      able to catalyze the formation of glycosides without competing hydrolysis.
      Finally, a short overview of the use of glycosyl fluorides as substrates and
      inhibitors of phosphorylases and phosphoglucomutase is given.

PMID- 10968676
TI  - Synthesis of deoxyfluoro sugars from carbohydrate precursors.
AB  - Results obtained over the past decade concerning the introduction of the fluorine
      atom into carbohydrate molecules, either by nucleophilic substitution or
      electrophilic addition reactions, are summarised. The first section mainly deals
      with the triflate/fluoride tandem sequence and the DAST-reaction. In the
      discussion, emphasis is given to the dependency of the reaction course on the
      stereochemical and protecting group features. Possible reaction pathways are
      direct substitution (with inversion or retention of configuration), rearrangement
      (combined with substitution and inversion of configuration at both of the centres
      involved) and elimination. Based on the assumption of cyclic transition states or
      transient intermediates (formed through participation of neighbouring groups),
      far-reaching mechanistic generalisations were made. On this basis, isolated
      examples from the literature, which are not in accordance with these
      generalisations, are specifically brought to attention. Results from the recently
      introduced reaction of safe and easy to handle N-F fluorinating agents with
      glycals are also reported. This approach allows the simple and stereoselective
      access to a series of 2-deoxy-2-fluoro aldopyranoses, as well as the synthesis of
      various C-1-substituted derivatives by an easy one-pot reaction. However, the
      same method applied to furanoid glycals is rather poor with respect to
      stereoselectivity. Finally, considerations on the importance of fluorine-specific
      reactions of the S(N)-type in related fields of organic synthesis are made.

PMID- 10968677
TI  - Fluorinated nucleosides.
AB  - The synthesis and biological activity of deoxyfluoro nucleosides are reviewed.

PMID- 10968678
TI  - Preparation of fluorine-18 labelled sugars and derivatives and their application
      as tracer for positron-emission-tomography.
AB  - The usefulness of 18F-labelled carbohydrates, especially 2-deoxy-2-[18F]fluoro-D
      glucose, to study pathophysiological processes in man non-invasively using
      positron-emission-tomography (PET) led to a widespread investigation of different
      18F-labelled sugars and sugar derivatives. In consideration of the short half
      life of fluorine-18 (T(1/2) = 110 min) synthetic strategies concerning precursor
      design, labelling conditions and deprotection of the intermediate compounds were
      developed to guarantee an efficient high radiochemical yield synthesis for
      diagnostic purposes. Besides some aspects of medical application of 2-deoxy-2
      [18F]fluoro-D-glucose, a few synthetic strategies are described reflecting
      development work on promising 18F-labelled sugars for diagnostic purposes during
      the last two decades.

PMID- 10968679
TI  - C-Difluoromethylene-containing, C-trifluoromethyl and C-perfluoroalkyl
      carbohydrates. Synthesis by carbohydrate transformation or building block
      methods.
AB  - The synthetic methods for preparing carbohydrates bearing a C-branched
      substituent of the type CF2-Y, with Y = F, Y = CnF(2n + 1) or Y = a carbon
      attached or heteroatom-attached nonfluorinated residues, are reviewed. Both
      direct introduction of C-branched fluorinated substituents (direct
      trifluoromethylation, perfluoroalkylation or difluoromethylenation) and building
      block methods from fluorinated synthons are considered.

PMID- 10968680
TI  - Carbohydrate- and related polyol-derived fluorosurfactants: an update.
AB  - A short review of recent literature is presented on the synthesis, biological
      properties, colloid and surface chemistry, and applications of carbohydrate- and
      related polyol-derived amphiphiles with perfluoroalkyl hydrophobes.

PMID- 10968681
TI  - Liquid crystals based on fluorinated carbohydrates.
AB  - Fluorine introduced in the hydrophilic or the hydrophobic region of amphiphiles
      influences the thermomesomorphy of amphiphilic and monophilic fluorosugars in a
      very specific manner. This paper is the first review about chiral mesogens based
      on fluorinated carbohydrates. It covers the literature published so far.
      Analytical objectives are given to: (i) Effects of fluorine atoms on the H
      bonding network of the hydrophilic region of sugar amphiphiles; (ii) Effects of
      perfluoroalkyl chains compared to alkyl chains; (iii) Polymorphism, e.g., also
      formation of smectic S(C)* phases.

PMID- 10968682
TI  - NMR spectra of fluorinated carbohydrates.
AB  - Recent advances in structural and conformational analysis of fluorinated
      carbohydrates by NMR spectroscopy are reviewed. Characteristic 1H, 13C, and 19F
      NMR chemical shifts and coupling constants for selected examples are given and
      the spectral data of a series of fluorinated carbohydrates were collected in
      continuation of the review of Csuk and Glanzer [Adv. Carbohydr. Chem. Biochem.,
      46 (1988) 73-177].

PMID- 10968684
TI  - Dismal rehabilitation in predominantly type II diabetics on dialysis in Inner
      City Brooklyn.
AB  - AIM: In order to define their demographics and medical conditions, 218 diabetic
      patients undergoing hemodialysis in Brooklyn were interviewed and their charts
      reviewed. METHODS: Patient rehabilitation was assessed with the Karnofsky score,
      and the urea reduction rate as well as serum albumin and hematocrit levels
      evaluated adequacy of hemodialysis. RESULTS: The majority of patients (167) were
      African-American, 25 were Whites, 19 patients were Hispanic and 6 were Asian. One
      patient was a Native American. The mean age was 60.5 years (range 16-88), and the
      majority, 52%, were women. Rehabilitation was poor, the mean Karnofsky score
      being 65.1+/-20.8, and only 6% of patients were working. By linear regression,
      there was no difference in the Karnofsky score according to gender, age, race,
      type of diabetes, education, family income or hematocrit level. Only the
      patients' self-perception of their psyche function, or how well they thought they
      were doing, was significant. CONCLUSION: Further work is needed to examine the
      reasons for the poor rehabilitation of diabetics on dialysis in Brooklyn.

PMID- 10968683
TI  - High sodium chloride intake is associated with low bone density in calcium stone
      forming patients.
AB  - BACKGROUND: Although renal stone disease has been associated with reduced bone
      mass, the impact of nutrient intake on bone loss is unknown. SUBJECTS AND
      METHODS: The present study was undertaken to investigate the influence of
      nutrient intake on bone density of 85 calcium stone-forming (CSF) patients (47
      male and 38 premenopausal females) aged 41+/-11 years (X+/-SD). Bone mineral
      density (BMD) was measured using dual energy X-ray absorptiometry at the lumbar
      spine (L2-L4) and femoral neck sites, and low BMD was defined as a T score < -1
      (WHO criteria). A 4-day dietary record and a 24-hour urine sample were obtained
      from each patient for the assessment of nutrient intake and urinary calcium
      (U(Ca)), sodium (U(Na)), phosphate and creatinine excretion. RESULTS: Forty-eight
      patients (56%) presented normal BMD and 37 (44%) low BMD. There were no
      statistical differences regarding age, weight, height, body mass index, protein,
      calcium and phosphorus intakes between both groups. The mean U(Ca), phosphorus
      and nitrogen appearance also did not differ between groups. However, there was a
      higher percentage of hypercalciuria among low vs normal BMD patients (62 vs 33%,
      p < 0.05). Low BMD patients presented a higher mean sodium chloride (NaCl) intake
      and excretion (UNa) than normal BMD (14+/-5 vs 12+/-4 g/day and 246+/-85 vs 204+/
      68 mEq/day, respectively p < 0.05). The percentage of patients presenting NaCl
      intake > or = 16 g/day was also higher among low vs normal BMD patients (35 vs
      12%, p < 0.05). After adjustment for calcium and protein intakes, age, weight,
      body mass index, urinary calcium, citrate and uric acid excretion, and duration
      of stone disease, multiple-regression analysis showed that a high NaCl intake (>
      or = 16 g/day) was the single variable that was predictive of risk of low bone
      density in CSF patients (odds ratio = 3.8). CONCLUSION: These data suggest that
      reducing salt intake should be recommended for CSF patients presenting
      hypercalciuria and osteopenia.

PMID- 10968685
TI  - A trial of two iron-dextran infusion regimens in chronic hemodialysis patients.
AB  - AIM: To test the ability to elicit a hemoglobin (Hb) response in patients on
      chronic hemodialysis, we prospectively compared two regimens of iron dextran
      administration, 100 mg once weekly (QW) or 100 mg once every dialysis (QD), both
      given for 10 doses. PATIENTS AND METHODS: Twenty-three consecutive patients on
      chronic hemodialysis received iron dextran intravenously if they had absolute or
      functional iron deficiency. There was no difference in the Hb response between
      regimens. RESULTS: Both groups had a significant increase in Hb from 10.5+/-1.5
      g/dl at baseline, to 11.1+/-1.7 g/dl at 1 month, 1.4+/-2.1 g/dl at 2 months and
      11.6+/-1.9 g/dl at 3 months. The increment in Hb at 1 month was similar (QD
      0.62+/-1.245 g/dl vs. QW 0.64+/-1.464 g/dl) between the two groups despite a
      large difference in the amount of iron received. Serum ferritin, transferrin
      saturations or epoetin dose did not change significantly. At the end of 3 months
      12 patients did not need further iron therapy as judged by the serological
      markers of iron stores. Of these 12 patients, 3 had serum ferritins of > 1,000
      ng/ml. Weekly dosing of iron was associated with more medication errors than
      dosing every dialysis. Baseline iron stores could not predict the responsiveness
      to intravenous iron therapy as judged by an increase in Hb concentration at 1
      month or at 3 months. CONCLUSION: This study confirms the efficacy of 1,000 mg of
      intravenous iron administered over a 3-month period in patients with functional
      iron deficiency. It underscores the importance of careful monitoring of iron
      stores and highlights the need for developing better parameters of functional
      iron stores in hemodialysis patients.

PMID- 10968686
TI  - Hemodialysis-related subacromial lesion: diagnostic imaging and minimally
      invasive treatment.
AB  - BACKGROUND: In an attempt to refine the diagnosis and surgical treatment system
      for spontaneous shoulder pain in supine position (SPSP) in long-term hemodialysis
      (LTHD) patients we reviewed shoulders of patients during a 4-year period.
      PATIENTS AND METHODS: Clinical findings, imaging findings and operative results
      (average duration of follow-up was 39 months) on both shoulders of 110 patients
      (Shigei Hospital, Okayama, Japan) were analyzed to identify the cause of SPSP in
      order to accurately differentiate it from other shoulder pains, and to select the
      proper treatment method. RESULTS: As the hemodialysis period lengthened, increase
      in the incidence and severity of bone and soft tissue changes (radiolucency,
      joint destruction, increase of thickness of subacromial bursa and rotator cuff,
      and synovial proliferation) in the shoulder induced by dialysis-related
      amyloidosis were noted in roentgenography, ultrasonography and magnetic resonance
      imaging. SPSP occurred in the LTHD patients. An increase in subacromial bursa and
      rotator cuff thickness correlated with SPSP. A decrease in subacromial space
      correlated with change in position and SPSP. An increase of subacromial pressure
      was judged to be the cause of SPSP, and subacromial decompression by coraco
      acromial ligament release was effective for relieving SPSP. When massive synovial
      proliferation or invasion of granulation tissues was observed in the glenohumeral
      joint, arthroscopic debridement was necessary. CONCLUSION: SPSP is a sensitive
      indicator of a distinct subacromial lesion frequently found in LTHD patients.
      These lesions can be treated by minimally invasive endoscopic coraco-acromial
      ligament release, resulting in marked pain relief.

PMID- 10968687
TI  - Pentosan polysulfate decreases proliferation and extracellular matrix deposition
      by vascular smooth muscle cells isolated from failed hemodialysis access grafts.
AB  - BACKGROUND: Vascular access failure is a major cause of morbidity, and increased
      costs in patients undergoing maintenance hemodialysis. Stenosis, the most common
      underlying cause of loss of patency in failed grafts, appears to be caused by an
      obstructing mass of tissue containing proliferating smooth muscle cells and their
      associated extracellular matrix. METHODS: To determine whether this process was
      amenable to pharmacologic intervention and/or prevention, we obtained samples of
      the material occluding vascular accesses from 7 patients undergoing revision
      surgery in order to characterize the cells contributing to the stenosis. In all 7
      patients the outgrowth contained predominantly smooth muscle-like cells admixed
      with fibroblasts, which produced a large amount of type IV and type I collagen.
      RESULTS: Treatment with pentosan polysulfate inhibited cell proliferation and
      significantly reduced the accumulation of types I and type IV collagens. This was
      associated with increase in metalloproteinase-9 (MMP-9) and a shift of tissue
      inhibitor of metalloproteinase-3 (TIMP-3) from the cell layer into the medium.
      CONCLUSION: These data suggest that pentosan polysulfate (PPS) may have a
      favorable effect in patients with a polytetrafluoroethylene (PFTE) graft by
      decreasing cell proliferation and collagen deposition.

PMID- 10968688
TI  - Effects of "isolating hemodialysis" on prevention of methicillin-resistant
      Staphylococcus aureus cross-infection in a hemodialysis unit.
AB  - AIM: To evaluate the effects of a contact isolation program against methicillin
      resistant Staphylococcus aureus (MRSA) cross-infection among patients in a
      hemodialysis unit. CLINICAL SETTING AND METHODS: In all patients maintaining
      hemodialysis therapy were tested for MRSA infection and who had MRSA infection,
      not only inpatients but also outpatients were separated into a designated area
      (isolating hemodialysis). Clinically isolated MRSA strains were clonotyped with
      coagulase typing, staphylococcal enterotoxin typing and restriction enzyme
      analysis of plasmid DNA. RESULTS: The frequency of patients with MRSA infection
      was 4.5% before starting this protocol and was reduced to 2.9% two and a half
      years later. At this time, MRSA was isolated from the 8 patients. These 8
      clinical strains were differentiated into 6 clonotypes and 3 strains showed the
      same patterns. Two of 3 were isolated from inpatients and the other was from a
      patient with community onset MRSA colitis. In this case, most MRSA infections
      were independent under prophylaxis control and cross-infection was observed only
      once between hospitalized patients who stayed in a same ward. CONCLUSION: This
      "isolating hemodialysis" should be useful to prevent cross-infection among
      patients in end-stage renal disease in a dialysis unit.

PMID- 10968689
TI  - The outcome of tuberculosis in patients on chronic hemodialysis.
AB  - AIM: In patients on regular hemodialysis, the incidence of tuberculosis is high.
      MATERIAL: We present 18 (6.08%) tuberculosis patients among 296 patients on
      regular hemodialysis between 1980 and 1996. RESULTS: Pulmonary tuberculosis was
      seen in 11 (61%) patients, 7 (38%) of whom presented with pleural effusion.
      Tuberculosis was extrapulmonary in 7 (38%) patients. There were 4 (22.2%)
      patients with tuberculous lymphadenitis, 2 (11.1%) with tuberculous peritonitis,
      1 (5.5%) with urinary tuberculosis. Intermittent fever, malasia and dyspnea were
      the most common symptoms. The mean duration on hemodialysis before diagnosis of
      tuberculosis were 22.22+/-7.19 months and the mean duration of symptoms prior to
      treatment were 34.16+/-3.36 days. Tuberculosis was diagnosed in 10 (55.5%)
      patients within the first 4 months of dialysis and in 8 (44.4%) between the 1st
      and the 8th year of hemodialysis treatment. Our patients were treated with
      isoniazid, rifampicin, morfazinamid and ethambutol. Four patients died within the
      first 4 months of the antituberculosis therapy, in all of whom tuberculosis was
      diagnosed within the 4 months of dialysis. In patients who died, duration of
      symptoms ranged from 30 days to 60 days, mean 42 days. Overall mortality was
      22.2% and correlated with the duration of symptoms prior to initiation of
      antituberculosis and hemodialysis therapy. Fourteen patients (77.7%) who survived
      longer than one year were clinically cured. CONCLUSION: Our results suggest that
      the mortality of tuberculosis is high in patients in the early phase of
      maintenance dialysis and delay in the disease treatment of tuberculosis. Because
      of their generally poor state of nutrition, and depressed cellular immunity, the
      mortality is high in patients in the early stage of maintenance hemodialysis.
      Therefore, if the diagnosis is delayed, mortality is higher. Tuberculosis should
      be considered strongly and treated promptly if suspected.

PMID- 10968690
TI  - The safety and efficacy of GM-CSF as an adjuvant in hepatitis B vaccination of
      chronic hemodialysis patients who have failed primary vaccination.
AB  - BACKGROUND: End-stage renal disease and the need for chronic hemodialysis is an
      indication for hepatitis B vaccination, but up to half of dialysis patients fail
      to respond to a 40 microg/dose i.m. three-dose primary series of recombinant
      hepatitis B vaccine. Only another 10-20% respond to additional boosting doses of
      vaccine. PATIENTS AND METHODS: Since GM-CSF has been shown to be an effective
      adjuvant for hepatitis B vaccine in healthy subjects and multiple animal vaccine
      models, we conducted a randomized, double-blind trial of GM-CSF with recombinant
      hepatitis B vaccine in chronic hemodialysis patients. Patients with negative
      hepatitis B surface antibody and antigen who had received at least three doses of
      recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml)
      were randomized to placebo, 40 microg, or 80 microg of GM-CSF given with 40
      microg recombinant hepatitis B vaccine i.m. at the same site. Clinical and
      laboratory studies for safety assessment were done on days 1 and 3, and hepatitis
      B surface antibody titres were measured at baseline and days 21 and 180 after the
      study injections. RESULTS: No significant local or systemic toxicity was noted
      from the co-injections. The rates of response and geometric mean titre (GMT) were
      equivalent among all three study groups: placebo 6/10 developed antibodies, GMT
      22.1 mIU/ml; 40 microg GM-CSF 3/10 developed antibodies, GMT 5.4 mIU; and 80
      microg GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after
      vaccination, antibody titres were available for 11 of the 12 day 21 positive
      responders; only 4 of these 11 patients remained antibody positive at 6 months.
      CONCLUSION: GM-CSF given in a single 40 microg and 80 microg i.m. dose was not an
      effective adjuvant with hepatitis B vaccine in chronic hemodialysis patients who
      had previously failed to respond to hepatitis B immunization.

PMID- 10968691
TI  - Hepatitis C virus in the hemodialysis setting: detecting viral RNA from blood
      port caps by reverse transcription-polymerase chain reaction.
AB  - BACKGROUND: A widely observed increased risk of hepatitis C virus (HCV) infection
      in chronic hemodialysis patients has been previously attributed to violations of
      "Universal Precautions" for the control of blood-borne pathogens, as well as in
      part, to other risk factors, such as a history of blood transfusion or injection
      drug use. However, specific factors responsible for transmission have not been
      identified and the possibility that flaws in dialysis procedures, including
      sterilization, could increase the risk of transmission, has not been excluded.
      METHODS: We investigated reuse procedures for hemodialysis equipment and tested
      dialyzer blood port caps for detection of hepatitis C virus RNA (HCV RNA) by
      reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Following
      artificial contamination of the blood port caps with blood or fluids from human
      HCV-positive patients, and overnight soaking in 1% Renalin, HCV RNA was detected
      on 4 of 20 caps contaminated with blood, 1 of 10 contaminated with serum and 8 of
      24 contaminated with dialyzer blood compartment residue. HCV RNA was also
      detected on 1 of 111 pairs of blood port caps collected post dialysis from HCV
      positive patients, after soaking the caps overnight in 1% Renalin. CONCLUSION:
      The results suggest that HCV RNA might be detectable on reused dialysis equipment
      post sterilization procedures, if residual blood or serum is not entirely or
      almost entirely removed prior to sterilization. This may warrant evaluation of
      sterilization procedures to ensure that procedures are adequate and that
      protocols are rigorously followed. Further studies of sterilization procedures by
      sensitive techniques such as RT-PCR may be indicated.

PMID- 10968692
TI  - Expression of macrophage migration inhibitory factor in patients with
      myeloperoxidase anti-neutrophil cytoplasmic antibody-associated
      glomerulonephritis.
AB  - AIM AND METHODS: To investigate the relationship between macrophage migration
      inhibitory factor and clinical or pathological findings in patients with
      myeloperoxidase anti-neutrophil cytoplasmic antibody MPO-ANCA-associated
      glomerulonephritis characterized by idiopathic necrotizing crescentic
      glomerulonephritis, renal biopsy specimens from 16 patients with MPO-ANCA
      associated glomerulonephritis and 15 controls were stained using an enzyme
      antibody method to detect macrophage migration inhibitory factor and macrophages
      infiltrating the glomeruli. The relationship of this factor with various clinical
      parameters and with cellular crescents was determined. RESULTS: Macrophage
      migration inhibitory factor was detected in 11 out of 16 patients with MPO-ANCA
      associated glomerulonephritis, but was not found in any of the controls. In the
      positive patients, the blood MPO-ANCA level was significantly higher than in the
      negative patients. Both cellular crescents and the number of macrophages
      infiltrating the glomeruli were significantly increased in the patients positive
      for macrophage migration inhibitory factor. CONCLUSION: Thus, macrophage
      migration inhibitory factor may be closely related to cellular crescent formation
      and disease activity in patients with MPO-ANCA-associated glomerulonephritis.

PMID- 10968693
TI  - High ALT levels predict viremia in anti-HCV-positive HD patients if a modified
      normal range of ALT is applied.
AB  - AIMS: Some studies have reported that ALT determination is of little value in the
      study of chronic hepatitis C in hemodialysis (HD) patients. This could be due to
      the fact that ALT values are lower in HD patients than in healthy individuals;
      ALT in HCV infection follows a fluctuating pattern and the HCV viremia may be
      intermittent. The aim of this study was to establish the reference ALT values in
      a large group of hepatitis-free HD patients, and to determine their role in
      predicting viremia in anti-HCV-positive HD patients. METHODS: Four subject groups
      were studied: group I, patients with normal renal function (n = 88); group II,
      hepatitis-free HD patients (n = 218); group III, non-viremic anti-HCV+ HD
      patients (n = 9); and group IV, viremic anti-HCV+ HD patients (n = 24). The ALT
      used for calculation purposes was the mean value of the twelve previous months
      for each individual patient. PCR screening for HCV-RNA was performed at least
      twice for anti-HCV+ patients; these were deemed viremic (HCV-RNA+) if at least
      one screening was positive, and non-viremic (HCV-RNA) if all PCR results were
      negative. RESULTS: Mean ALT in group II was lower than in subjects with normal
      renal function (15.6 +/- 12 vs. 22.7 +/- 18 IU/l, p < 0.05). No significant
      differences were observed between group III and group II (17.7 +/- 6 vs. 15.6 +/-
      6 IU/l, ns). ALT levels in group IV patients were higher than those of groups II
      and III (38.5 +/- 39 IU/l, p < 0.05). The upper limit (mean + 2 SD and 95th
      percentile) for ALT in hepatitis-free HD patients was 27 IU/l. Sensitivity of a
      mean ALT value > or = 27 IU/l in the diagnosis of HCV viremia was 50%, and
      specificity was 100%. The positive predictive value of this test in the diagnosis
      of hepatitis C viremia was 100%. CONCLUSIONS: ALT values are lower in HD patients
      and a high ALT level can constitute an excellent tool in predicting viremia in
      anti-HCV-positive HD patients once other causes of liver disease have been
      excluded.

PMID- 10968694
TI  - Inappropriate antidiuresis associated with pituitary adenoma--mechanisms not
      involving inappropriate secretion of vasopressin.
AB  - We report an unusual case of inappropriate antidiuresis with undetectable
      vasopressin in an elderly man presenting with confusion due to severe
      hyponatremia. Further investigations led to the diagnosis of non-functional
      pituitary macroadenoma. The patient had normal thyroid and adrenal function. The
      abnormal water balance resolved promptly after transsphenoidal removal of the
      tumor, confirmed by a repeat water loading test. We conclude that inappropriate
      antidiuresis in the absence of excess vasopressin secretion may implicate mass
      effect from an underlying pituitary tumor.

PMID- 10968695
TI  - Transformation of hepatitis B virus-related membranous glomerulonephritis to
      crescentic form.
AB  - We report a case of hepatitis B virus-(HBV) related membranous glomerulonephritis
      which progressed to crescentic transformation after withdrawal of
      immunosuppressive treatment. Immunosuppressive therapy probably enhanced HBV
      replication, and its withdrawal led to a return of immune competence resulting in
      progression of the glomerulonephritis. Prior screening of all patients for
      hepatitis B surface antigen, before using immunosuppressive therapy may prevent
      this complication. The usage of immunosuppressive therapy as a first-line choice
      in HBV-related glomerulonephritis may result in harmful complications.

PMID- 10968696
TI  - A case of mixed connective tissue disease (MCTD) complicated with MPO-ANCA
      related necrotizing glomerulonephritis.
AB  - Renal diseases of mixed connective tissue disease (MCTD) are not unusual.
      Although most of them are SLE-like renal impairment with immune complex deposits,
      systemic sclerosis- (SSc) like renal impairments with intimal thickening of
      interlobular arteries or arterioles are also encountered. Several cases of SSc
      complicated with MPO-ANCA-related necrotizing glomerulonephritis (nGN) are
      reported. Here we report a case which developed MPO-ANCA-related nGN 16 years
      after the diagnosis of MCTD. She exhibited pauci-immune focal nGN and
      significantly high titer of MPO-ANCA. She was successfully treated with
      prednisolone and cyclophosphamide. We believe this is the first case in which MPO
      ANCA-related nGN was demonstrated in a patient with MCTD.

PMID- 10968697
TI  - Acute poststreptococcal glomerulonephritis associated with thrombotic
      microangiopathy in an adult.
AB  - The simultaneous occurrence of acute poststreptococcal glomerulonephritis and
      thrombotic microangiopathy is rare. A 47-year-old woman was admitted with acute
      renal failure, hematuria, edematous nephrotic syndrome and severe hypertension.
      This acute nephritic syndrome occurred two weeks after left leg erysipelas. The
      patient also had signs of intravascular hemolysis, low serum levels of C3 and C4
      and elevated antistreptolysin-O titer. Kidney biopsy confirmed postinfectious
      glomerulonephritis with diffuse hypercellularity and humps, and simultaneous
      subendothelial hyalin deposits and fibrinoid arteriolar thrombi. The patient
      received four antihypertensive drugs, acetylsalicyclic acid and plasma infusions.
      Renal function improved, hypertension was controlled and serum levels of C3 and
      C4 complement components returned to normal within three months. This case
      illustrates the occurrence of thrombotic microangiopathy in association with
      acute poststreptococcal glomerulonephritis. This simultaneous appearance supports
      a role of neuraminidase in this disease.

PMID- 10968698
TI  - Reply to Satomura.

PMID- 10968699
TI  - Causes of peritoneal calcifications in CAPD. Reply to Kitoh et al.

PMID- 10968701
TI  - RPA provides guidance on the role of the nephrologist as the dialysis facility
      medical director. Renal Physicians Association.

PMID- 10968700
TI  - Patients with IgA nephropathy whose renal function remains stable for a long time
      even after exceeding the "point of no return".

PMID- 10968702
TI  - Advances in immunohistochemistry: impact on surgical pathology practice.
AB  - Over the past decade, the many advances in immunohistochemical techniques have
      revolutionized the field of immunohistochemistry. Most notable is discovery of
      the use of heat for antigen retrieval, which permits consistent and reliable
      demonstration of antigens in routine surgical pathology specimens despite
      variations in the duration of fixation and tissue processing schedules. As a
      result, immunohistochemical studies play an increasingly important role in
      surgical pathology, such as help in rendering a diagnosis in a crushed specimen,
      classification of tumors, prediction of the likely origin of a carcinoma,
      demonstration of micrometastases, provision of prognostic information, and
      demonstration of microorganisms. To serve such purposes, immunohistochemical
      stains must be performed at a high standard with consistent and reproducible
      results. The stains must be interpreted cautiously in the appropriate context,
      and potential pitfalls such as endogenous biotin activity must be recognized. The
      increased demand for immunohistochemical tests raises the issue of cost
      containment, which can be achieved through a number of ways, such as deletion of
      nonvalue-added tests, deletion of antibodies that no longer serve a purpose,
      replacement of the conventional positive control with a multitissue control
      mounted on the same slides of the test cases, various means of savings on
      antibodies, and continuing to use "expired" antibodies. To keep abreast of modem
      developments in the field in this era of information explosion, the internet can
      play an important role by providing updated information or database and a
      platform for rapid exchange of knowledge.

PMID- 10968703
TI  - The role of immunohistochemistry in the diagnosis of malignant mesothelioma.
AB  - The immunohistochemical diagnosis of mesothelioma is perhaps one of the most
      perplexing and controversial issues in surgical pathology. A tumor that in
      essence is extremely rare has managed to captivate the attention not only of
      pulmonologists and thoracic surgeons but also of pathologists. Throughout its
      history, mesothelioma has emerged as one of the tumors that has evaded definitive
      characterization; hence, the numerous attempts at trying to establish not only
      histological criteria but also histochemical, immunohistochemical, and
      ultrastructural guidelines for its diagnosis. Perhaps as we enter an era of more
      sophisticated technology, molecular biology will have an opportunity to make
      inroads into the diagnosis and characterization of this peculiar neoplasm.
      Despite the many difficulties involved in the diagnosis of malignant
      mesothelioma, we have recently gained significant knowledge of this entity in
      many respects, several decades after its description. From a morphological point
      of view, several variations of the histological appearances that these tumors may
      exhibit have been described. Traditional histochemistry and electron microscopy
      continue to play an important role in the evaluation of these neoplasms, with
      ultrastructural analysis in particular representing the most reliable technique
      for making this diagnosis in equivocal cases. However, because of its speed, cost
      effectiveness, and general availability, immunohistochemistry has emerged as the
      most commonly used procedure for the diagnosis of mesotheliomas. We herein
      present a review of the current status of immunohistochemical evaluation of
      malignant lesions that are suspected of having a mesothelial lineage.

PMID- 10968704
TI  - Immunohistologic evaluation of metastatic carcinomas of unknown origin: an
      algorithmic approach.
AB  - Pathologists are now asked frequently to determine the primary site for
      metastatic carcinomas of unknown origin (MCUO), using adjunctive morphological
      techniques such as electron microscopy, immunohistology, and other modalities.
      The authors present an algorithmic immunohistochemical approach to this problem
      that is based on their experience with over 2,800 routinely-processed epithelial
      malignancies of various types. These have been studied with antibodies to
      keratins, vimentin, epithelial membrane antigen, MOC-31, tumor associated
      glycoprotein-72 (recognized by monoclonal antibody B72.3), prostate-specific
      antigen, thyroglobulin, gross cystic disease fluid protein-15, carcinoembryonic
      antigen, CA-125, CA19-9, placental alkaline phosphatase, S100 protein, and
      estrogen receptor protein. The algorithm that is structured around these 14
      analytes is based on the relative predictive value of each marker, which in turn,
      determines its place in the sequence of interpretation. The authors' experience
      with this approach shows 67% accuracy with regard to the ultimately determined
      site of origin for MCUO, a figure which is similar to that reported by other
      investigators.

PMID- 10968705
TI  - Immunohistology of neuroendocrine and neuroectodermal tumors.
AB  - Neuroendocrine and neuroectodermal tumors are interrelated, and comprise a
      neoplastic family including lesions formerly termed "carcinoid," "atypical
      carcinoid," "small cell undifferentiated carcinoma," "primitive
      neuroepithelioma," "chemodectoma," and "neuroblastoma," to name but a few
      entities. The nosology of these neoplasms has been simplified recently, in part
      as a result of a better understanding of their immunophenotypes and molecular
      biological attributes. This review considers those immunohistochemical markers
      that are now generally available for diagnostic evaluation of neuroendocrine and
      neuroectodermal differentiation, and provides information on the relative
      sensitivity and specificity of each of them. Intermediate filament proteins,
      chromogranins, synaptophysin, CD56, CD57, CD99, neuron-specific (gamma-dimer)
      enolase, protein gene product 9.5, and specific neuropeptide products are
      discussed. The application of such determinants in regional differential
      diagnosis is also summarized.

PMID- 10968706
TI  - Immunohistochemistry in the diagnosis of neoplasms of the central nervous system.
AB  - The diagnosis and evaluation of neoplasms of the central nervous system
      frequently involves the use of immunohistochemical stains. This article reviews
      some of the more commonly used markers including glial fibrillary acidic protein,
      synaptophysin, neurofilament protein, S-100 protein, epithelial membrane antigen,
      and cytokeratin markers. The focus of the discussion is on the use of these
      markers including their utility in resolving differential diagnostic issues. We
      also review the use of p53 and a variety of cell proliferation markers including
      proliferating cell nuclear antigen, Ki-67, MIB-1 and their potential role as
      adjuncts in the grading of tumors and their potential role in predicting tumor
      behavior.

PMID- 10968707
TI  - Immunohistochemistry of small round-cell tumors.
AB  - The term "small round-cell tumor" describes a group of highly aggressive
      malignant tumors composed of relatively small and monotonous undifferentiated
      cells with high nuclear to cytoplasmic ratios. This group includes Ewing's
      sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor
      or extraskeletal ES), peripheral neuroblastoma ("classic-type"),
      rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small
      cell osteosarcoma, small-cell carcinoma (either undifferentiated or
      neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma
      (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal
      chondrosarcoma. Their clinical presentations often overlap, thus making a
      definitive diagnosis problematic in some cases. Yet, a clear understanding of
      their clinicopathologic features usually allows for a confident diagnosis,
      especially if immunohistochemistry is used. The following is a review of the
      immunohistochemistry of this small round-cell tumor group.

PMID- 10968708
TI  - Recent advances in the application of immunohistochemical markers for the
      diagnosis of soft tissue tumors.
AB  - Soft tissue tumors represent a frequent source of diagnostic difficulty for
      surgical pathologists. Over the past 20 years, immunohistochemical studies have
      emerged as a powerful and helpful tool for the assessment and characterization of
      these lesions. Although much progress has been made in this field, the continuous
      realization of the relative lack of specificity and broad overlap in reactivity
      for the various tumor markers among these lesions has contributed to limit
      somewhat their usefulness and reliability in this area of tumor diagnosis.
      However, with the advent of new markers has come the new promise of better and
      more accurate distinction and characterization for these tumors. Herein we will
      review the current status of immunohistochemical tumor markers in the diagnosis
      of soft tissue neoplasms and address some of the more recently described
      antibodies and their relative value and limitations for the diagnosis of these
      tumors.

PMID- 10968709
TI  - Immunophenotyping of hematopoietic neoplasms.
AB  - Advances in the staging and treatment of hematopoietic neoplasms have
      necessitated a high degree of accuracy in the diagnosis and classification of
      these tumors. A greater degree of diagnostic precision has resulted from recent
      advances in immunophenotyping and genotyping of hematopoietic neoplasms. This
      review discusses several new immunohistochemical reagents, many of which are
      derived from results of molecular studies.

PMID- 10968710
TI  - Costs and benefits of measures to prevent needlestick injuries in a university
      hospital.

PMID- 10968711
TI  - Evaluation of hospital infection rates and control measures in a cardiac surgery
      hospital: 10 years' experience.

PMID- 10968712
TI  - Effect of dispensers and hand antiseptic on hand hygiene.

PMID- 10968713
TI  - Medical-device reprocessing.

PMID- 10968714
TI  - Cleaning of blood-contaminated reprocessed angiographic catheters and spinal
      needles.
AB  - OBJECTIVES: To evaluate the efficacy of a multistep cleaning method using a
      cleaner and a chemical disinfectant on blood-contaminated angiographic catheters
      and spinal needles intended to be sterilized by hydrogen peroxide gas plasma.
      METHOD: A mixture of radiopaque iodine contrast, bovine blood (plus
      ethylenediaminetetraacetic acid), and a suspension of Bacillus subtilis spores
      was used to simulate catheterization and needle use. The mixture was a 1:1
      proportion of contrast and blood, inoculated so that there was a final
      concentration of B subtilis spores of 1.0x10(6) colony-forming units (CFU)/mL.
      The inoculated devices were cleaned using a hydrogen peroxide solution at a
      concentration of 1.5+/-0.5 percent by weight, followed by distilled water with
      enzymatic detergent. After drying, the devices were sterilized with hydrogen
      peroxide gas plasma. RESULTS: The initial B subtilis spore concentration
      inoculated into catheters and needles varied from 2.12x10(4) to 2.74x10(7)
      CFU/mL. The residual load of B. subtilis spores after cleaning varied from zero
      (no count) to a maximum of 200 CFU/device. The multistep cleaning procedure was
      responsible for an average 5log10 reduction of B. subtilis spores in the catheter
      and needle lumens. CONCLUSIONS: The hydrogen peroxide and enzymatic detergent
      aqueous solutions were shown to be efficacious when used as part of a multistep
      cleaning method. The low level of microbial contamination prior to sterilization
      with hydrogen peroxide gas plasma assured that the intended sterility assurance
      level was reached.

PMID- 10968715
TI  - Pathogenic organisms associated with artificial fingernails worn by healthcare
      workers.
AB  - OBJECTIVE: To determine differences in the identity and quantity of microbial
      flora from healthcare workers (HCWs) wearing artificial nails compared with
      control HCWs with native nails. DESIGN: Two separate studies were undertaken. In
      study 1, 12 HCWs who did not normally wear artificial nails wore polished
      artificial nails on their nondominant hand for 15 days. Identity and quantity of
      microflora were compared between the artificial nails and the polished native
      nails of the other hand. In study 2, the microbial flora of the nails of 30 HCWs
      who wore permanent acrylic artificial nails were compared with that of control
      HCWs who had native nails. In both studies, nail surfaces were swabbed and
      subungual debris was collected to obtain material for culture. Staphylococcus
      aureus, gram-negative bacilli, enterococci, and yeasts were considered to be
      potential pathogens. All organisms were identified and quantified. RESULTS: In
      study 1, potential pathogens were isolated from more samples obtained from
      artificial nails than native nails (92% vs. 62%; P<.001). Colonization of
      artificial nails increased over time; by day 15, 71% of cultures yielded a
      pathogen compared with 21% on day 1 (P=.004). A significantly greater quantity of
      organisms (expressed as mean log10 colony-forming units +/- standard deviation)
      was isolated from the subungual area than the nail surface; this was noted for
      both artificial (5.0+/-1.4 vs. 4.1+/-1.0; P<.001) and native nails (4.9+/-1.3 vs.
      3.7+/-0.8; P<.001). More organisms were found on the surface of artificial nails
      than native nails (P=.008), but there were no differences noted in the quantities
      of organisms isolated from the subungual areas. In study 2, HCWs wearing
      artificial nails were more likely to have a pathogen isolated than controls (87%
      vs. 43%; P=.001). More HCWs with artificial nails had gram-negative bacilli (47%
      vs. 17%; P=.03) and yeasts (50% vs. 13%; P=.006) than control HCWs. However, the
      quantities of organisms isolated from HCWs wearing artificial nails and controls
      did not differ. CONCLUSIONS: Artificial fingernails were more likely to harbor
      pathogens, especially gram-negative bacilli and yeasts, than native nails. The
      longer artificial nails were worn, the more likely that a pathogen was isolated.
      Current recommendations restricting artificial fingernails in certain healthcare
      settings appear justified.

PMID- 10968716
TI  - Nosocomial infections in combined medical-surgical intensive care units in the
      United States.
AB  - OBJECTIVE: To describe the epidemiology of nosocomial infections in combined
      medical-surgical (MS) intensive care units (ICUs) participating in the National
      Nosocomial Infection Surveillance (NNIS) System. DESIGN: Analysis of surveillance
      data on 498,998 patients with 1,554,070 patient-days, collected between 1992 and
      1998 from 205 MS ICUs following the NNIS Intensive Care Unit protocol,
      representing 152 participating NNIS hospitals in the United States. RESULTS:
      Infections at three major sites represented 68% of all reported infections
      (nosocomial pneumonia, 31%; urinary tract infections (UTIs), 23%; and primary
      bloodstream infections (BSIs), 14%: 83% of episodes of nosocomial pneumonia were
      associated with mechanical ventilation, 97% of UTIs occurred in catheterized
      patients, and 87% of primary BSIs in patients with a central line. In patients
      with primary BSIs, coagulase-negative staphylococci (39%) were the most common
      pathogens reported; Staphylococcus aureus (12%) was as frequently reported as
      enterococci (11%). Coagulase-negative staphylococcal BSIs were increasingly
      reported over the 6 years, but no increase was seen in candidemia or enterococcal
      bacteremia. In patients with pneumonia, S. aureus (17%) was the most frequently
      reported isolate. Of reported isolates, 59% were gram-negative bacilli. In
      patients with UTIs, Escherichia coli (19%) was the most frequently reported
      isolate. Of reported isolates, 31% were fungi. In patients with surgical-site
      infections, Enterococcus (17%) was the single most frequently reported pathogen.
      Device-associated nosocomial infection rates for BSIs, pneumonia, and UTIs did
      not correlate with length of ICU stay, hospital bed size, number of beds in the
      ICU, or season. Combined MS ICUs in major teaching hospitals had higher device
      associated infection rates compared to all other hospitals with combined medical
      surgical units. CONCLUSIONS: Nosocomial infections in MS ICUs at the most
      frequent infection sites (bloodstream, urinary, and respiratory tract) almost
      always were associated with use of an invasive device. Device-associated
      infection rates were the best available comparative rates between combined MS
      ICUs, but the distribution of device-associated rates should be stratified by a
      hospital's major teaching affiliation status.

PMID- 10968717
TI  - Activity of an alcohol-based hand gel against human adeno-, rhino-, and
      rotaviruses using the fingerpad method.
AB  - OBJECTIVE: To assess the activity against three non-enveloped viruses (an adeno-,
      a rhino- and a rotavirus) of a gel containing 60% ethanol, using experimentally
      contaminated thumb- and fingerpads of 12 panelists, as per standard procedure E
      1838-96 of the American Society of Testing and Materials. DESIGN: Each digit
      received 10 microL of the test virus suspension. The inoculum from the thumbs was
      eluted immediately with 990 microL of Earle's balanced salt solution (EBSS) to
      assess the amount of virus on each digit (0-minute control). The inoculum on the
      fingers was allowed to dry (20-25 minutes), and virus was eluted from two
      fingerpads to determine the loss in virus infectivity upon drying (baseline
      titer). Then the dried inoculum on randomly selected fingers was exposed to 1 mL
      of the test product or standard hard water (200-ppm calcium carbonate) for 20
      seconds. The virus remaining was eluted with 1 mL of EBSS, titrated to determine
      the amounts eliminated, and compared to the baseline titer. RESULTS: Each digit
      received at least 10(4) plaque-forming units of virus in 10 microL. The amounts
      of adeno-, rhino-, and rotaviruses surviving the drying were 30%, 75%, and 42%,
      respectively. The product reduced the infectivity titers of the three viruses by
      3 to >4 log10 when compared to a reduction of < or =1 log10 for the hard-water
      rinse. CONCLUSION: The level of virus reduction by gel was statistically
      significantly higher than that seen with the water control. Evidence for such
      activity against non-enveloped viruses supports further investigation of the
      benefits of this product.

PMID- 10968718
TI  - Prevalence and determinants of fecal colonization with vancomycin-resistant
      Enterococcus in hospitalized patients in The Netherlands.
AB  - OBJECTIVE: To determine the prevalence and determinants of fecal carriage of
      vancomycin-resistant enterococci (VRE) in intensive care unit (ICU), hematology
      oncology, and hemodialysis patients in The Netherlands. DESIGN: Descriptive,
      multicenter study, with yearly 1-week point-prevalence assessments between 1995
      and 1998. POPULATION: All patients hospitalized on the testing days in ICUs and
      hematology-oncology wards in nine hospitals in The Netherlands were included.
      METHODS: Rectal swabs obtained from 1,112 patients were screened for enterococci
      in a selective broth and subcultured on selective media with and without 6 mg/L
      vancomycin. Resistance genotypes were determined by polymerase chain reaction.
      Further characterization of VRE strains was done by pulsed-field gel
      electrophoresis (PFGE). We studied possible determinants of VRE colonization with
      a logistic regression analysis model. Determinants analyzed included gender, age,
      and log-transformed length of prior hospital stay. RESULTS: The results showed
      that 614 (55%) of 1,112 patients were colonized with vancomycin-sensitive
      enterococci, and 15 (1.4%) of 1,112 carried VRE. No increase in VRE colonization
      was observed from 1995 to 1998. Eleven strains were identified as Enterococcus
      faecium and four as Enterococcus faecalis. All E faecium and one E faecalis
      carried the vanA gene; the other E faecalis strains harbored the vanB gene. PFGE
      revealed that three vanB VRE isolated from patients hospitalized in one single
      ICU were related, suggesting nosocomial transmission. Though higher age seemed
      associated with VRE colonization, exclusion of patients with the nosocomial
      strain from the regression analysis decreased this relation to nonsignificant.
      Duration of hospital stay was not associated with VRE colonization. CONCLUSION:
      VRE colonization in Dutch hospitals is an infrequent phenomenon. Although
      nosocomial spread occurs, most observed cases were unrelated, which suggests the
      possibility of VRE acquisition from outside the hospital. Prolonged hospital
      stay, age, and gender proved unrelated to VRE colonization.

PMID- 10968719
TI  - Use of spoligotype analysis to detect laboratory cross-contamination.
AB  - Spoligotype analysis identified false-positive isolates of Mycobacterium
      tuberculosis caused by laboratory cross-contamination. Spoligotyping is faster,
      is less expensive than DNA fingerprinting, and can be used with a variety of
      media. Patients were reevaluated and had medications discontinued as a result of
      this investigation. Months of unnecessary patient follow-up and treatment were
      avoided.

PMID- 10968720
TI  - Epidemiology of nosocomial outbreaks: 14-year experience at a tertiary-care
      center.
AB  - Twelve nosocomial outbreaks over 14 years at a tertiary-care center in Mexico are
      described. Overall mortality was 25.8%, one half due to pneumonia. The most
      common organism was Pseudomonas aeruginosa. Incidence was three outbreaks per
      10,000 discharges; outbreak-related infections comprised 1.56% of all nosocomial
      infections. Incidence in the intensive care unit was 10-fold higher.

PMID- 10968721
TI  - Transient detection of plasma HIV-1 RNA during postexposure prophylaxis.
AB  - Transient plasma human immunodeficiency virus (HIV) copies were detected by
      nucleic-acid sequence-based amplification during combination antiretroviral
      prophylaxis in a healthcare worker who reported a percutaneous injury from a
      stylet and who remained HIV-antibody-negative. An HIV-specific T-helper response,
      assessed by interleukin-2 production, was observed when tested at 13 months
      following the exposure.

PMID- 10968722
TI  - A pilot study on infection control in 10 randomly selected European hospitals:
      results of a questionnaire survey.
AB  - We describe and compare the organization of infection control and some infection
      control practices in 10 hospitals in seven different European countries. Great
      differences were observed. By evaluating infection control and hygiene practices
      in different European centers, areas of prime importance for the development of a
      European infection control standard may be defined.

PMID- 10968723
TI  - Nosocomial infections in a new medical center, Turkey.
AB  - Nosocomial infection was found in 255 (2.5%) of 10,164 inpatients in a new
      medical center with a 310-bed capacity. The infection rate was 12.5% in the
      intensive care unit, 9.5% in neurology, 5.5% in general surgery, and 4.0% in
      orthopedics. Rates in the other services were lower. Hospital-acquired infections
      in our medical center frequently involved multiply resistant Enterobacteriaceae
      and staphylococci.

PMID- 10968724
TI  - Antimicrobial use in long-term-care facilities. SHEA Long-Term-Care Committee.
AB  - There is intense antimicrobial use in long-term-care facilities (LTCFs), and
      studies repeatedly document that much of this use is inappropriate. The current
      crisis in antimicrobial resistance, which encompasses the LTCF, heightens
      concerns of antimicrobial use. Attempts to improve antimicrobial use in the LTCF
      are complicated by characteristics of the patient population, limited
      availability of diagnostic tests, and the virtual absence of relevant clinical
      trials. This position paper recommends approaches to management of common
      infections in LTCF patients and proposes minimal standards for an antimicrobial
      review program. In developing these recommendations, the position paper
      acknowledges the unique aspects of provision of care in the LTCF.

PMID- 10968725
TI  - Studies on the disinfection of VRE-contaminated surfaces.

PMID- 10968726
TI  - Comparability of resting energy expenditure in Nigerians and U.S. blacks.
AB  - OBJECTIVE: To determine the influence of environmental factors on resting energy
      expenditure (REE) and its relationship to adiposity in two populations of West
      African origin, Nigerians and U.S. blacks. RESEARCH METHODS AND PROCEDURES: REE
      and body composition were measured in a cross-sectional sample of 89 Nigerian
      adults (39 women and 50 men), and 181 U.S. black adults (117 women and 65 men).
      Both groups represent randomly selected population samples. REE was measured by
      indirect calorimetry after an overnight fast in both sites using the same
      instrument. Body composition was estimated using bioelectrical impedance analysis
      (BIA) in 72 Nigerians and 156 U.S. participants. Multivariate regression analysis
      was used to determine the significant predictors of REE. The analyses were
      repeated in a set of 17 Nigerians and 28 U.S. blacks in whom body composition was
      measured using deuterium dilution. RESULTS: U.S. black adults were significantly
      heavier and had both more fat-free mass (FFM) and body fat than Nigerians. FFM
      was the only significant determinant of REE in both population groups, whether
      body composition was measured using BIA or deuterium dilution. The relationship
      between REE and body composition did not differ by site. There was no
      relationship between REE and adiposity. DISCUSSION: Differences in current
      environmental settings did not impact REE. The differences observed in mean
      levels of body fat between Nigerians and U.S. blacks were not the result of
      differences in REE adjusted for body composition.

PMID- 10968727
TI  - Resemblance for body mass index in families of obese African American and
      European American women.
AB  - OBJECTIVE: We determined the levels of resemblance in body mass index (BMI) in
      large samples of families selected through obese African American and European
      American women. RESEARCH METHODS AND PROCEDURES: We examined correlations among
      relatives in 1,185 European American and African American families ascertained
      through age-matched obese women (BMI > or = 30 kg/m2). A subset of 801 families
      were ascertained through extremely obese women (BMI > or = 40 kg/m2). RESULTS:
      Parent-offspring and sibling correlations ranged from 0.19 to 0.15, suggesting a
      moderate level of heritability in both groups. Mean BMI values for female
      relatives were lower for European Americans than for African Americans even
      though probands were matched, perhaps because the European American relatives
      regress to a lower population mean. We found significantly higher family
      correlations for height in European Americans, suggesting greater environmental
      variability among African Americans for factors affecting growth and physical
      development. DISCUSSION: Our results suggest a similar level of heritability of
      BMI in families of obese African American and European American women. Other
      genetic studies will be needed to determine the extent to which the same or
      different genes and environmental conditions contribute to an overall similar
      heritability in the two racial groups.

PMID- 10968728
TI  - Predictors of weight change in middle-aged and old men.
AB  - OBJECTIVE: Studies on weight change and mortality have yielded inconclusive
      results. This 10-year prospective study was undertaken to improve understanding
      of factors affecting weight change. RESEARCH METHODS AND PROCEDURES: The subjects
      were 1,143 men, aged 36 to 88 years (mean, 53.3 years) at entry. A questionnaire
      was filled in at entry and at the end of the follow-up with queries on weight,
      height, weight at the age of 20, physician-diagnosed diseases, smoking, alcohol
      use, dietary habits, leisure physical activity, occupation, present occupational
      activity, living conditions (living alone or cohabiting), and former athletic
      status. Further information on morbidity was obtained from selected national
      registers. Factors predicting weight change during the study were identified by
      stepwise linear multiple regression analysis. RESULTS: The mean 10-year weight
      change was 0.8 (range, -29 to +24) kg. Age at entry (beta-coefficient, -0.17, SE
      0.02), weight at entry (beta, -0.03, SE 0.01), diabetes at entry (beta, -3.55, SE
      1.02), diabetes diagnosed after entry (beta, -3.94, SE 0.96), malignant cancer
      (beta, -1.60, SE 0.70), being a smoker (beta, - 1.59, SE 0.48), and increased
      physical activity (beta, - 1.27, SE 0.54) were significantly (p < 0.05)
      associated with weight loss in the final model. The model explained 13% of the
      variance of weight change. DISCUSSION: The results emphasize the complexity of
      weight change. Some factors associated with weight change are apparently
      negatively, and some positively, associated with health. This could explain the
      equivocal findings on weight change and mortality in the literature.

PMID- 10968729
TI  - Partial genome scale analysis of gene expression in human adipose tissue using
      DNA array.
AB  - OBJECTIVE: Large scale analysis of gene expression in adipose tissue provides a
      basis for the identification of novel candidate genes involved in the
      pathophysiology of obesity. Our goal was to explore gene expression in human
      adipose tissue at a partial genome scale using DNA array. RESEARCH METHODS AND
      PROCEDURES: Labeled cDNA, derived from human adipose tissue poly(A+) RNA, was
      hybridized to a DNA array containing over 18,000 human expressed sequence-tagged
      (EST) clones. The results were analyzed by database searches. RESULTS: Homology
      searches of the 300 EST clones with highest hybridization signals revealed that
      145 contained DNA sequences identical to known genes and 79 could be linked to
      UniGene clusters. Of the 145 identified genes, 136 were nonredundant and
      subsequently characterized with respect to function and chromosomal localization
      by searching MEDLINE, UniGene, GeneMap, OMIM, SWISS-PROT, the Genome Database,
      and the Location Data Base. The identified genes were grouped according to their
      putative functions; cell/organism defense (9.6%), cell division (5.1%), cell
      signaling/communication (19.8%), cell structure/motility (12.5%), gene/ protein
      expression (16.9%), metabolism (16.2%), and unclassified (19.8%). Less than 50%
      of these genes have previously been reported to be expressed in adipose tissue.
      The chromosomal localization of 268 genes strongly expressed in adipose tissue
      showed that their relative abundance was significantly increased on chromosomes
      11, 19, and 22 compared to the expected distribution of the same number of random
      genes. DISCUSSION: Our study resulted in the identification of numerous genes
      previously not reported to be expressed in adipose tissue. These results suggest
      that DNA array is a powerful tool in the search for novel regulatory pathways
      within adipose tissue on a scale that is not possible using conventional methods.

PMID- 10968730
TI  - Defective dietary induction of uncoupling protein 3 in skeletal muscle of obesity
      prone rats.
AB  - OBJECTIVE: The goal of this study was to determine whether differential induction
      of skeletal muscle uncoupling protein 3 (UCP3) contributes to the development of
      diet-induced obesity (DIO) or resistance to the development of obesity (DR) when
      rats are placed on a moderate fat (31%) high energy (HE) diet. RESEARCH METHODS
      AND PROCEDURES: Gastrocnemius muscle was obtained from Sprague-Dawley rats that
      were identified as DIO-prone (n = 5) or DR (n = 5) on the basis of urinary
      norepinephrine excretion while consuming a chow diet. Muscle was also obtained
      from animals in the top tertile of weight gain (DIOHE, n = 5) and the bottom
      tertile of weight gain (DRHE, n = 5) after 2 weeks on the HE diet. UCP3 and actin
      mRNA levels were measured in all muscle samples by Northern analysis. To
      distinguish the effect of dietary energy content from the effect of obesity
      itself, we studied additional DIO and DR animals that had been returned to a chow
      diet for 10 weeks after consuming a HE diet for 10 weeks. RESULTS: The muscle
      UCP3/actin mRNA ratio in animals that resisted the development of obesity during
      2 weeks on the HE diet was 3-fold higher than in the other groups (DRHE = 3.24 +/
      0.83, DIOHE = 0.91 +/- 0.20, DIO-prone = 0.72 +/- 0.15, DR = 0.63 +/- 0.15; p =
      0.002). However, there was no difference in muscle UCP3/actin mRNA ratios between
      DIO animals and DR animals that had been fed the HE diet for 10 weeks and then
      returned to either an ad libitum chow diet for 10 weeks (DIO = 13.8 +/- 3.53, DR
      = 11.1 +/- 3.43, p = NS) or to a restricted chow diet for 10 weeks (DIO = 11.0 +/
      2.85, DR = 10.6 +/- 2.20, p = NS) despite significantly greater body weight of
      the DIO animals. DISCUSSION: DR animals may initially resist weight gain when
      placed on a HE diet through a greater induction of muscle UCP3. This induction is
      transient and is related more closely to dietary fat content than to body fat
      stores. DIO animals show no initial induction of muscle UCP3, which may
      contribute to their increased metabolic efficiency soon after exposure to a HE
      diet.

PMID- 10968731
TI  - Precision and accuracy of dual-energy X-ray absorptiometry for determining in
      vivo body composition of mice.
AB  - OBJECTIVE: To evaluate the precision and accuracy of dual-energy X-ray
      absorptiometry (DXA) for the measurement of total-bone mineral density (TBMD),
      total-body bone mineral (TBBM), fat mass (FM), and bone-free lean tissue mass
      (LTM) in mice. RESEARCH METHODS AND PROCEDURES: Twenty-five male C57BL/6J mice (6
      to 11 weeks old; 19 to 29 g) were anesthetized and scanned three times (with
      repositioning between scans) using a peripheral densitometer (Lunar PIXImus).
      Gravimetric and chemical extraction techniques (Soxhlet) were used as the
      criterion method for the determination of body composition; ash content was
      determined by burning at 600 degrees C for 8 hours. RESULTS: The mean
      intraindividual coefficients of variation (CV) for the repeated DXA analyses
      were: TBMD, 0.84%; TBBM, 1.60%; FM, 2.20%; and LTM, 0.86%. Accuracy was
      determined by comparing the DXA-derived data from the first scan with the
      chemical carcass analysis data. DXA accurately measured bone ash content (p =
      0.942), underestimated LTM (0.59 +/- 0.05g, p < 0.001), and overestimated FM
      (2.19 +/- 0.06g, p < 0.001 ). Thus, DXA estimated 100% of bone ash content, 97%
      of carcass LTM, and 209% of carcass FM. DXA-derived values were then used to
      predict chemical values of FM and LTM. Chemically extracted FM was best predicted
      by DXA FM and DXA LTM [FM = -0.50 + 1.09(DXA FM) - 0.11(DXA LTM), model r2 =
      0.86, root mean square error (RMSE) = 0.233 g] and chemically determined LTM by
      DXA LTM [LTM = -0.14 + 1.04(DXA LTM), r2 = 0.99, RMSE = 0.238 g]. DISCUSSION:
      These data show that the precision of DXA for measuring TBMD, TBBM, FM, and LTM
      in mice ranges from a low of 0.84% to a high of 2.20% (CV). DXA accurately
      measured bone ash content but overestimated carcass FM and underestimated LTM.
      However, because of the close relationship between DXA-derived data and chemical
      carcass analysis for FM and LTM, prediction equations can be derived to more
      accurately predict body composition.

PMID- 10968732
TI  - Metabolic and weight loss effects of long-term dietary intervention in obese
      patients: four-year results.
AB  - OBJECTIVE: To investigate the contribution of meal and snack replacements for
      long-term weight maintenance and risk factor reduction in obese patients.
      RESEARCH METHODS AND PROCEDURES: Prospective, randomized, two-arm, parallel
      intervention for 12 weeks followed by a prospective single-arm 4-year trial in a
      University Hospital clinic. One hundred patients, >18 years old and with a body
      mass index > 25 and < or = 40 kg/m2, were prescribed a 1,200 to 1,500 kcal/d
      control diet (Group A) or an isoenergetic diet, including two meal and snack
      replacements (vitamin- and mineral-fortified shakes, soups, and bars) and one
      meal high in fruits and vegetables (Group B). Following a 3 months of weight
      loss, all patients were prescribed the same energy-restricted diet (1,200 to
      1,500 kcal) with one meal and one snack replacement for an additional 4 years.
      RESULTS: All 100 patients were evaluated at 12 weeks. Mean percentage weight loss
      was 1.5 +/- 0.4% and 7.8 +/- 0.5% (mean +/- SEM) for Groups A and B,
      respectively. At 12 weeks systolic blood pressure, plasma triacylglycerol,
      glucose, and insulin concentrations were significantly reduced in Group B,
      whereas no changes occurred in Group A. After 4 years, 75% of the patients were
      evaluated. Total mean weight loss was 3.2 +/- 0.8% for Group A and 8.4 +/- 0.8%
      (mean +/- SEM) for Group B. Both groups showed significant improvement in blood
      glucose and insulin (p < 0.001), but only Group B showed significant improvement
      in triacylglycerol and systolic blood pressure compared to baseline values (p <
      0.001). DISCUSSION: Providing a structured meal plan via vitamin- and mineral
      fortified liquid meal replacements is a safe and effective dietary strategy for
      obese patients. Long-term maintenance of weight loss with meal replacements can
      improve certain biomarkers of disease risk.

PMID- 10968733
TI  - Access and use of medical care among obese persons.
AB  - The prevalence of obesity and severe obesity is growing rapidly, along with
      obesity-related comorbidities and mortality. Given the increased health risks
      associated with obesity, it is vital that obese persons have adequate access to,
      and make consistent use of, medical care services. Assuming obese persons have
      access to medical care that is comparable to non-obese persons, one would expect
      to observe greater use of medical services among obese persons. In this article
      we briefly review empirical evidence of the access to and use of medical care
      among obese persons. Although certain subgroups that tend to have
      disproportionately high prevalences of obesity (i.e., low socioeconomic status,
      minority groups) have reduced access to care, no studies have specifically
      examined whether or not obese persons have the same access to health care as do
      their lean counterparts. With respect to use of health care services, however,
      obesity has been consistently linked with greater rates of utilization and
      increased health care expenditures. Both the increased use and cost appear to be
      largely a function of treating obesity-associated comorbidities such as diabetes
      and hypertension. We conclude that, although it is clear that obesity is
      associated with both greater use and cost of medical care, the relationship
      between obesity and access to medical care has not been determined.

PMID- 10968734
TI  - Role of environmental vs. metabolic factors in the etiology of obesity: time to
      focus on the environment.

PMID- 10968735
TI  - NRA on gun ownership.

PMID- 10968736
TI  - Docs for guns.

PMID- 10968737
TI  - Self-reported swimming ability in US adults, 1994.

PMID- 10968739
TI  - First-ever surgeon general's report on oral health identifies disparities.

PMID- 10968738
TI  - Cultural competence.

PMID- 10968740
TI  - Girl power! Education kit available.

PMID- 10968741
TI  - Healthy communities: a young movement that can revolutionize public health. A
      short history and some acknowledgments.

PMID- 10968742
TI  - The healthy communities movement and the coalition for healthier cities and
      communities.
AB  - Part One of this article describes the principles and origins of the Healthy
      Communities movement. Part Two describes the Coalition for Healthier Cities and
      Communities, a national network of partnerships and organizations. The authors
      argue (a) that to sustain community initiatives, practitioners must move from
      projects that address symptoms of social problems to changing the underlying
      community cultures, incentives, and settings that give rise to these symptoms,
      and (b) that the Coalition's continued relevance depends on its ability to help
      leaders make that transition.

PMID- 10968743
TI  - Twelve years and counting: California's experience with a statewide Healthy
      Cities and Community program.
AB  - California Healthy Cities and Communities is the longest running statewide
      program of its kind in the nation. After providing a brief history the authors
      give an overview of the supporting activities and resources the Program provides
      to Healthy Cities and Communities initiatives throughout California.

PMID- 10968744
TI  - Key components of a statewide Healthy Communities effort.
AB  - The Healthy Cities/Healthy Communities movement is in its second decade. Examples
      of both successful and unsuccessful Healthy Communities efforts can be found in
      large and small communities across the country. What are the key components of a
      successful effort? Movement leaders from California, Massachusetts, Pennsylvania,
      and South Carolina as well as the Centers for Disease Control (CDC) and
      Prevention have contributed their collective experience to identifying the key
      components of a statewide Healthy Communities effort. Assessing the degree to
      which a state has these key components in place can help the state take steps to
      assure support for Healthy Communities.

PMID- 10968745
TI  - Building communities that create health.
AB  - Typically, public health policy, program design, and resource allocation are
      based on issue-specific, targeted interventions directed at specific populations
      or sub-populations. The authors argue that this approach fails to meet the goal
      of public health-to improve health for all--and that the key to health
      improvement is to create a social context in which healthy choices are the norm.
      The authors present as case studies two Pennsylvania cities that used
      multisectoral approaches to achieve community health improvements.

PMID- 10968746
TI  - Caring relationships: an investment in health?
AB  - Although the US has created the most expensive, technologically advanced medical
      system in the world, health outcomes are not commensurate with investment. The
      author argues that providers and policy makers have neglected the effect of human
      relationships on health, citing research showing that better relationships lead
      to better health. The author concludes with recommendations for improving public
      health by supporting society's investments in social capital.

PMID- 10968747
TI  - Healthy communities must also be sustainable communities.
AB  - The author contends that healthy communities must be both environmentally and
      socially sustainable, given that health depends on the quality of the built and
      natural environments, and that global change resulting from the industrial
      economy is affecting the web of life. He argues that suburban sprawl wastes
      scarce resources and disproportionately places those resources in the hands of
      suburban dwellers. Urban areas can be made more environmentally sustainable,
      especially with respect to energy consumption, which will help reduce air
      pollution and climate change and contribute in other ways to improved health.

PMID- 10968748
TI  - Toward a healthy democracy.
AB  - Because it represents a revival of citizen responsibility, the Healthy
      Communities movement is not only a health and quality-of-life movement but a
      civic and democratic movement as well. Healthy Communities efforts need to seek
      meaningful partnerships with local governments and work their collaborative and
      citizen-based efforts into formal local political structures. As the foundation
      of the Healthy Communities movement, civic renewal should be elevated as a major
      theme and goal for its future.

PMID- 10968749
TI  - Community-building: from local wisdom to public policy.
AB  - The authors argue that social changes have caused the rupture of communal life in
      our neighborhoods and that the answer is community-building: strengthening
      communities holistically, fostering participation and problem-solving, addressing
      issues of bigotry and poverty, and engaging institutions to work as partners with
      residents.

PMID- 10968750
TI  - Supportive communities for children and families.
AB  - Starting from the premise that strong families are a key factor in building
      healthy communities, the author recounts what children need to become productive
      members of society and what families need to help children succeed. The author
      describes what communities can do to help families and calls for the public will
      to support families as they struggle to raise healthy, successful children.

PMID- 10968751
TI  - A model memorandum of collaboration: a proposal.
AB  - The authors propose a model memorandum of collaboration for use by state and
      community partnerships, support organizations, and grantmakers in working
      together to build healthier communities. Described as an idealized social
      contract, the model memorandum lays out interrelated responsibilities for the key
      parties.

PMID- 10968752
TI  - Commentaries from grantmakers on Fawcett et al.'s proposed memorandum of
      collaboration.

PMID- 10968753
TI  - Using Participatory Action Research to build Healthy Communities.
AB  - The author contends that community-based Participatory Action Research (PAR) is
      ideally suited for use in Healthy Communities projects. The article begins by
      defining PAR and its principles and characteristics, then discusses the
      philosophical and methodological compatibility of PAR and Healthy Communities.
      After highlighting the challenges of expanding the Healthy Communities accent on
      participation to include PAR, the article describes the experiences of two
      Healthy Communities projects in the US that have successfully used PAR.

PMID- 10968754
TI  - A participatory evaluation model for Healthier Communities: developing indicators
      for New Mexico.
AB  - Participatory evaluation models that invite community coalitions to take an
      active role in developing evaluations of their programs are a natural fit with
      Healthy Communities initiatives. The author describes the development of a
      participatory evaluation model for New Mexico's Healthier Communities program.
      She describes evaluation principles, research questions, and baseline findings.
      The evaluation model shows the links between process, community-level system
      impacts, and population health changes.

PMID- 10968755
TI  - Assets-oriented community assessment.
AB  - Determining how to promote community health requires that community health
      workers first assess where the community stands. The authors maintain that
      Healthy Communities initiatives are better served by assets-oriented assessment
      methods than by standard "problem-focused" or "needs-based" approaches. An assets
      orientation allows community members to identify, support, and mobilize existing
      community resources to create a shared vision of change, and encourages greater
      creativity when community members do address problems and obstacles.

PMID- 10968756
TI  - Healthy Communities and public policy: four success stories.
AB  - As Healthy Communities initiatives mature, many of them are discovering that
      their work in building community consensus for improved health care and other
      quality-of-life issues can be transformed into public policy. This article shows
      how Healthy Communities initiatives have had important effects on policy making
      at both the county and state level in several cities and states.

PMID- 10968757
TI  - The city government's role in community health improvement.
AB  - Amid increasing pressures to address complex issues not traditionally assigned to
      localities, Healthy Cities is seen as a powerful model for community improvement
      and quality-of-life enhancements for individuals and organizations willing to
      think beyond the traditional local government management models and
      responsibilities. As a model for community-oriented government, it offers
      opportunities for fostering a return to "barnraising" concepts, civic
      responsibility, participation, tailoring solutions to local circumstances, and
      the transition of local government to governance models.

PMID- 10968758
TI  - Schools as catalysts for healthy communities.
AB  - Four school superintendents with a shared commitment to students' needs were able
      to forge a coalition that brought positive change to an entire region. Helping
      students and their families was a rallying issue for all community agencies.
      Initially, the four districts joined to apply for grant funding to link schools
      and social services providers. This served as a model and catalyst for many other
      cooperative community efforts.

PMID- 10968759
TI  - The school as the center of a healthy community.
AB  - Educational institutions have long been an important focus for public health
      initiatives. Their readily accessible populations of young people provide an
      excellent forum for health education, vaccination, and other public health
      interventions. However, schools can also play an important role as various
      sectors of the community seek to build new relationships. This article explores
      opportunities for public health leadership in strengthening schools, an important
      community asset.

PMID- 10968760
TI  - Engaging colleges and universities as partners in Healthy Communities
      initiatives.
AB  - Colleges and universities have an important role to play in building healthier
      communities. In many communities, however, these institutions are viewed with
      mistrust and skepticism, not as partners or assets. Academics often fail to
      respect and value community resources; they often assume the role of experts when
      they approach communities, in the context of short-term projects that place a
      priority on their goals rather than on communities' goals. Yet, colleges and
      universities have much to contribute as partners with their communities, and
      there are many strategies that can be used to develop community-campus
      partnerships. Whether the leadership for such a partnership starts with the
      community or the campus is not particularly important as long as the
      collaboration moves forward in a way that honors and values the strengths and
      assets of each.

PMID- 10968761
TI  - Healthy Communities and civil discourse: a leadership opportunity for public
      health professionals.
AB  - The author argues that the Healthy Communities movement provides public health
      professionals with an opportunity to become not just community leaders but also
      agents of change in a broad political sense. Extending the work of Kohlberg and
      other developmental psychologists, the author describes five levels of civil
      discourse. Professionals who practice the inclusive, consensus-oriented level of
      discourse, which is consistent with the philosophy of Healthy Communities, can
      help reinvigorate civil society and democracy as a part of making their
      communities healthier.

PMID- 10968762
TI  - Improving collaboration between researchers and communities.
AB  - Active collaboration between communities and researchers is critical to
      developing appropriate public health research strategies that address community
      concerns. To capture the perspectives of inner-city Seattle communities about
      issues in community-researcher partnerships, Seattle Partners for Healthy
      Communities conducted interviews with community members from the ethnically
      diverse neighborhoods of Central and Southeast Seattle. The results suggest that
      effective community-researcher collaborations require a paradigm shift from
      traditional practices to an approach that involves: acknowledging community
      contributions, recruiting and training minority people to participate in research
      teams, improving communication, sharing power, and valuing respect and diversity.

PMID- 10968763
TI  - Police as contributors to Healthy Communities: Aiken, South Carolina.
AB  - In Aiken, South Carolina, community policing has led to numerous innovative
      programs that have contributed to a healthy community. The MOMS and COPS
      (Managing Our Maternity System with Community Oriented Policing System) program
      has played a significant part in the county's 50% decrease in infant mortality
      since 1989 and contributed to Aiken's designation as an All-America City in 1997.
      Other programs include a mentoring program for at-risk teen girls; instant crime
      reporting with donated cellular phones; seminars for seniors to alert them to
      scams and common crimes; demolition of unsafe homes; free installation of smoke
      detectors; a child ID program; and parental education on child brain development.

PMID- 10968764
TI  - A park for all the people.
AB  - A small park in downtown Oakland, California, has been a focal point for
      community-building and neighborhood improvement. This effort embodies the Healthy
      Cities cooperative approach to promoting social justice and positive community
      change. The story of the revitalization of this park is a story of individual and
      personal actions that collectively have shaped policy and strategy to improve the
      quality of life in this city.

PMID- 10968765
TI  - Backing onto sacred ground.
AB  - It is widely recognized that the health of individuals and communities is
      determined by the interaction of physical, mental, social, and spiritual factors.
      Public health leaders can find precedent for the resulting holistic strategies in
      the collaboration with religious structures that characterized the early years of
      public health. The modern context is more pluralistic, democratic, and complex in
      terms of its institutional array of partners.

PMID- 10968766
TI  - A "community as resource" strategy for disaster response.
AB  - Natural and technological disasters present significant threats to the public's
      health. The emergency response capabilities of government and private relief
      organizations are limited. With a strategy in which residents of urban areas are
      trained in search and rescue, first aid, fire suppression, care and shelter,
      emergency communications, and disaster mental health, the community becomes a
      "resource" rather than a "victim."

PMID- 10968767
TI  - Integrating Healthy Communities concepts into health professions training.
AB  - To meet the demands of the evolving health care system, health professionals need
      skills that will allow them to anticipate and respond to the broader social
      determinants of health. To ensure that these skills are learned during their
      professional education and training, health professions institutions must look
      beyond the medical model of caring for communities. Models in Seattle and Roanoke
      demonstrate the curricular changes necessary to ensure that students in the
      health professions are adequately prepared to contribute to building Healthy
      Communities in the 21st century. In addition to these models, a number of
      resources are available to help promote the needed institutional changes.

PMID- 10968768
TI  - Health information community networks.
AB  - The author supports the development of health information community networks
      (HICNs) as an important tool for use by individuals and community groups. HICNs
      can enable citizens, organizations, and communities to exchange geographically
      based information on community health status. Through HICNs, individuals and
      groups will be able to share information, prioritize issues, resolve conflicts,
      estimate the impact of policy initiatives, and plan, organize, manage, and
      evaluate programs and projects that deal with community health issues.

PMID- 10968769
TI  - The Community Tool Box: a Web-based resource for building healthier communities.
AB  - Building healthier cities and communities requires an array of community-building
      skills that are not always taught in formal education. The Community Tool Box
      (http://ctb.ukans.edu) is an Internet-based resource for practical,
      comprehensive, accessible, and user-friendly information on community-building,
      which both professionals and ordinary citizens can use in everyday practice. It
      connects people, ideas, and resources, offering more than 200 how-to sections and
      more than 5,000 pages of text.

PMID- 10968770
TI  - Healthy Cities: a guide to the literature.
AB  - The author reviews the literature on attempts by city governments, international
      agencies, and nongovernmental and community organizations to improve city life
      around the world through Healthy Cities projects.

PMID- 10968772
TI  - Mechanism of Phosphorus-Carbon Bond Cleavage in Tertiary Phosphines. An Optimized
      Synthesis of 1,2-Bis(phenylphosphino)ethane.

PMID- 10968773
TI  - A Simple Method for the Selective Deprotection of p-Methoxybenzyl Ethers by
      Cerium(III) Chloride Heptahydrate and Sodium Iodide.

PMID- 10968771
TI  - Linking public health academia to public health practice through program
      evaluation.

PMID- 10968774
TI  - Synthesis and Reactivity of Bicycles Derived from Tartaric Acid and alpha-Amino
      Acids: A Novel Class of Conformationally Constrained Dipeptide Isosteres Based
      upon Enantiopure 3-Aza-6,8-dioxabicyclo

PMID- 10968775
TI  - Transmission/disequilibrium tests using multiple tightly linked markers.
AB  - Transmission/disequilibrium tests have attracted much attention in genetic
      studies of complex traits because (a) their power to detect genes having small to
      moderate effects may be greater than that of other linkage methods and (b) they
      are robust against population stratification. Highly polymorphic markers have
      become available throughout the human genome, and many such markers can be
      studied within short physical distances. Studies using multiple tightly linked
      markers are more informative than those using single markers. However, such
      information has not been fully utilized by existing statistical methods,
      resulting in possibly substantial loss of information in the identification of
      genes underlying complex traits. In this article, we propose novel statistical
      methods to analyze multiple tightly linked markers. Simulation studies comparing
      our methods versus existing methods suggest that our methods are more powerful.
      Finally, we apply the proposed methods to study genetic linkage between the
      dopamine D2 receptor locus and alcoholism.

PMID- 10968776
TI  - Mapping of the locus for cholestasis-lymphedema syndrome (Aagenaes syndrome) to a
      6.6-cM interval on chromosome 15q.
AB  - Patients with cholestasis-lymphedema syndrome (CLS) suffer severe neonatal
      cholestasis that usually lessens during early childhood and becomes episodic;
      they also develop chronic severe lymphedema. The genetic cause of CLS is unknown.
      We performed a genome screen, using DNA from eight Norwegian patients with CLS
      and from seven unaffected relatives, all from an extended pedigree. Regions
      potentially shared identical by descent in patients were further characterized in
      a larger set of Norwegian patients. The patients manifest extensive allele and
      haplotype sharing over the 6.6-cM D15S979-D15S652 region: 30 (83.3%) of 36
      chromosomes of affected individuals carry a six-marker haplotype not found on any
      of the 32 nontransmitted parental chromosomes. All Norwegian patients with CLS
      are likely homozygous for the same disease mutation, inherited from a shared
      ancestor.

PMID- 10968777
TI  - PEX3 is the causal gene responsible for peroxisome membrane assembly-defective
      Zellweger syndrome of complementation group G.
AB  - Peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome (ZS) and
      neonatal adrenoleukodystrophy are autosomal recessive diseases caused by defects
      in peroxisome assembly, for which 13 genotypes have been identified. Expression
      of the human peroxin Pex3p cDNA encoding a 373-amino-acid peroxisomal membrane
      protein morphologically and biochemically restored peroxisome biogenesis,
      including peroxisomal membrane assembly, in fibroblasts from PBDG-02, a patient
      with complementation group G (CG-G) ZS. Patient PBDG-02 carried a homozygous,
      inactivating mutation-a 97-bp deletion of nucleotide residues at positions 942
      1038-resulting in a 32-amino-acid truncation and in a frameshift inducing both a
      3-amino-acid substitution and a termination codon. Genomic PCR analysis revealed
      mutation of T-->G at eight bases upstream of the splicing site at the boundary of
      intron 10 and exon 11 of PEX3 gene, giving rise to a deletion of all of exon 11.
      When assessed by expression in a pex3 mutant of Chinese hamster ovary cells and
      the patient's fibroblasts, PBDG-02-derived PEX3 cDNA was found to be defective in
      peroxisome-restoring activity. These results provide evidence that PEX3 is a
      novel, pathogenic gene responsible for CG-G PBDs.

PMID- 10968778
TI  - Hypervariable sites in the mtDNA control region are mutational hotspots.
AB  - Hypervariable sites in human mtDNA are readily identified in evolutionary studies
      and are usually assumed to represent mutational hotspots. Recently, an
      alternative hypothesis was proposed that holds that hypervariable sites may
      instead reflect ancient mtDNA mutations that have been "shuffled" among different
      lineages via recombination. These hypotheses can be tested by examining the
      evolutionary rates for sites at which new mtDNA mutations are observed; if
      hypervariable sites are mutational hotspots, then newly arisen mtDNA mutations
      should occur preferentially at hypervariable sites. Results of this study show
      that both germline and somatic mtDNA mutations occur preferentially at
      hypervariable sites, which supports the view that hypervariable sites are indeed
      mutational hotspots.

PMID- 10968779
TI  - The osteoblast: a sophisticated fibroblast under central surveillance.
AB  - The study of the biology of osteoblasts, or bone-forming cells, illustrates how
      mammalian genetics has profoundly modified our understanding of cell
      differentiation and physiologic processes. Indeed, genetic-based studies over the
      past 5 years have revealed how osteoblast differentiation is controlled through
      growth and transcription factors. Likewise, the recent identification, using
      mutant mouse models, of a central component in the regulation of bone formation
      expands our understanding of the control of bone remodeling. This regulatory
      loop, which involves the hormone leptin, may help to explain the protective
      effect of obesity on bone mass in humans. In addition, it provides a novel
      physiologic concept that may shed light on the etiology of osteoporosis and help
      to identify new therapeutic targets.

PMID- 10968781
TI  - Therapeutic approaches to bone diseases.
AB  - The strength and integrity of our bones depends on maintaining a delicate balance
      between bone resorption by osteoclasts and bone formation by osteoblasts. As we
      age or as a result of disease, this delicate balancing act becomes tipped in
      favor of osteoclasts so that bone resorption exceeds bone formation, rendering
      bones brittle and prone to fracture. A better understanding of the biology of
      osteoclasts and osteoblasts is providing opportunities for developing
      therapeutics to treat diseases of bone. Drugs that inhibit the formation or
      activity of osteoclasts are valuable for treating osteoporosis, Paget's disease,
      and inflammation of bone associated with rheumatoid arthritis or periodontal
      disease. Far less attention has been paid to promoting bone formation with, for
      example, growth factors or hormones, an approach that would be a valuable adjunct
      therapy for patients receiving inhibitors of bone resorption.

PMID- 10968782
TI  - Coseismic and Postseismic Fault Slip for the 17 August 1999, M = 7.5, Izmit,
      Turkey Earthquake.
AB  - We use Global Positioning System (GPS) observations and elastic half-space models
      to estimate the distribution of coseismic and postseismic slip along the Izmit
      earthquake rupture. Our results indicate that large coseismic slip (reaching 5.7
      meters) is confined to the upper 10 kilometers of the crust, correlates with
      structurally distinct fault segments, and is relatively low near the hypocenter.
      Continued surface deformation during the first 75 days after the earthquake
      indicates an aseismic fault slip of as much as 0.43 meters on and below the
      coseismic rupture. These observations are consistent with a transition from
      unstable (episodic large earthquakes) to stable (fault creep) sliding at the base
      of the seismogenic zone.

PMID- 10968780
TI  - Bone resorption by osteoclasts.
AB  - Osteoporosis, a disease endemic in Western society, typically reflects an
      imbalance in skeletal turnover so that bone resorption exceeds bone formation.
      Bone resorption is the unique function of the osteoclast, and anti-osteoporosis
      therapy to date has targeted this cell. The osteoclast is a specialized
      macrophage polykaryon whose differentiation is principally regulated by
      macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin.
      Reflecting integrin-mediated signals, the osteoclast develops a specialized
      cytoskeleton that permits it to establish an isolated microenvironment between
      itself and bone, wherein matrix degradation occurs by a process involving proton
      transport. Osteopetrotic mutants have provided a wealth of information about the
      genes that regulate the differentiation of osteoclasts and their capacity to
      resorb bone.

PMID- 10968784
TI  - Enhanced Room-Temperature Geometric Magnetoresistance in Inhomogeneous Narrow-Gap
      Semiconductors.
AB  - A symmetric van der Pauw disk of homogeneous nonmagnetic indium antimonide with
      an embedded concentric gold inhomogeneity is found to exhibit room-temperature
      geometric magnetoresistance as high as 100, 9100, and 750,000 percent at magnetic
      fields of 0.05, 0.25, and 4.0 teslas, respectively. For inhomogeneities of
      sufficiently large diameter relative to that of the surrounding disk, the
      resistance is field-independent up to an onset field above which it increases
      rapidly. These results can be understood in terms of the field-dependent
      deflection of current around the inhomogeneity.

PMID- 10968783
TI  - Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR
      heterodimers.
AB  - Several nuclear hormone receptors involved in lipid metabolism form obligate
      heterodimers with retinoid X receptors (RXRs) and are activated by RXR agonists
      such as rexinoids. Animals treated with rexinoids exhibited marked changes in
      cholesterol balance, including inhibition of cholesterol absorption and repressed
      bile acid synthesis. Studies with receptor-selective agonists revealed that
      oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR
      heterodimeric partners that mediate these effects by regulating expression of the
      reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid
      synthesis, CYP7A1, respectively. Thus, these RXR heterodimers serve as key
      regulators of cholesterol homeostasis by governing reverse cholesterol transport
      from peripheral tissues, bile acid synthesis in liver, and cholesterol absorption
      in intestine.

PMID- 10968785
TI  - Evidence for Superfluidity in Para-Hydrogen Clusters Inside Helium-4 Droplets at
      0.15 Kelvin.
AB  - A linear carbonyl sulfide (OCS) molecule surrounded by 14 to 16 para-hydrogen
      (pH(2)) molecules, or similar numbers of ortho-deuterium (oD(2)) molecules,
      within large helium-4 ((4)He) droplets and inside mixed (4)He/(3)He droplets was
      investigated by infrared spectroscopy. In the pure (4)He droplets (0.38 kelvin),
      both systems exhibited spectral features that indicate the excitation of angular
      momentum around the OCS axis. In the colder (4)He/(3)He droplets (0.15 kelvin),
      these features remained in the oD(2) cluster spectra but disappeared in the pH(2)
      spectra, indicating that the angular momentum is no longer excited. These results
      are consistent with the onset of superfluidity, thereby providing the first
      evidence for superfluidity in a liquid other than helium.

PMID- 10968786
TI  - A Quantum State-Resolved Insertion Reaction: O((1)D) + H(2)(J = 0) --> OH((2)
      product operator product operator product operator, v, N) + H((2)S).
AB  - The O((1)D) + H(2) --> OH + H reaction, which proceeds mainly as an insertion
      reaction at a collisional energy of 1.3 kilocalories per mole, has been
      investigated with the high-resolution H atom Rydberg "tagging" time-of-flight
      technique and the quasiclassical trajectory (QCT) method. Quantum state-resolved
      differential cross sections were measured for this prototype reaction. Different
      rotationally-vibrationally excited OH products have markedly different angular
      distributions, whereas the total reaction products are roughly forward and
      backward symmetric. Theoretical results obtained from QCT calculations indicate
      that this reaction is dominated by the insertion mechanism, with a small
      contribution from the collinear abstraction mechanism through quantum tunneling.

PMID- 10968787
TI  - 92Nb-(92)Zr and the Early Differentiation History of Planetary Bodies.
AB  - The niobium-92-zirconium-92 ((92)Nb-(92)Zr) extinct radioactive decay system
      (half-life of about 36 million years) can place new time constraints on early
      differentiation processes in the silicate portion of planets and meteorites.
      Zirconium isotope data show that Earth and the oldest lunar crust have the same
      relative abundances of (92)Zr as chondrites. (92)Zr deficits in calcium-aluminum
      rich inclusions from the Allende meteorite constrain the minimum value for the
      initial (92)Nb/(93)Nb ratio of the solar system to 0.001. The absence of (92)Zr
      anomalies in terrestrial and lunar samples indicates that large silicate
      reservoirs on Earth and the moon (such as a magma ocean residue, a depleted
      mantle, or a crust) formed more than 50 million years after the oldest meteorites
      formed.

PMID- 10968788
TI  - A 22,000-Year Record of Monsoonal Precipitation from Northern Chile's Atacama
      Desert.
AB  - Fossil rodent middens and wetland deposits from the central Atacama Desert (22
      degrees to 24 degrees S) indicate increasing summer precipitation, grass cover,
      and groundwater levels from 16.2 to 10.5 calendar kiloyears before present (ky
      B.P.). Higher elevation shrubs and summer-flowering grasses expanded downslope
      across what is now the edge of Absolute Desert, a broad expanse now largely
      devoid of rainfall and vegetation. Paradoxically, this pluvial period coincided
      with the summer insolation minimum and reduced adiabatic heating over the central
      Andes. Summer precipitation over the central Andes and central Atacama may depend
      on remote teleconnections between seasonal insolation forcing in both
      hemispheres, the Asian monsoon, and Pacific sea surface temperature gradients. A
      less pronounced episode of higher groundwater levels in the central Atacama from
      8 to 3 ky B.P. conflicts with an extreme lowstand of Lake Titicaca, indicating
      either different climatic forcing or different response times and sensitivities
      to climatic change.

PMID- 10968789
TI  - Structural evidence for evolution of the beta/alpha barrel scaffold by gene
      duplication and fusion.
AB  - The atomic structures of two proteins in the histidine biosynthesis pathway
      consist of beta/alpha barrels with a twofold repeat pattern. It is likely that
      these proteins evolved by twofold gene duplication and gene fusion from a common
      half-barrel ancestor. These ancestral domains are not visible as independent
      domains in the extant proteins but can be inferred from a combination of sequence
      and structural analysis. The detection of subdomain structures may be useful in
      efforts to search genome sequences for functionally and structurally related
      proteins.

PMID- 10968790
TI  - Selective inhibition of NF-kappaB activation by a peptide that blocks the
      interaction of NEMO with the IkappaB kinase complex.
AB  - Activation of the transcription factor nuclear factor (NF)-kappaB by
      proinflammatory stimuli leads to increased expression of genes involved in
      inflammation. Activation of NF-kappaB requires the activity of an inhibitor of
      kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and
      IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino
      terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment
      of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell
      permeable NBD peptide blocked association of NEMO with the IKK complex and
      inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene
      expression. The peptide also ameliorated inflammatory responses in two
      experimental mouse models of acute inflammation. The NBD provides a target for
      the development of drugs that would block proinflammatory activation of the IKK
      complex without inhibiting basal NF-kappaB activity.

PMID- 10968791
TI  - Predictions of biodiversity response to genetically modified herbicide-tolerant
      crops.
AB  - We simulated the effects of the introduction of genetically modified herbicide
      tolerant (GMHT) crops on weed populations and the consequences for seed-eating
      birds. We predict that weed populations might be reduced to low levels or
      practically eradicated, depending on the exact form of management. Consequent
      effects on the local use of fields by birds might be severe, because such
      reductions represent a major loss of food resources. The regional impacts of GMHT
      crops are shown to depend on whether the adoption of GMHT crops by farmers
      covaries with current weed levels.

PMID- 10968792
TI  - Relation between population density and body size in stream communities.
AB  - The existence of a general relation between population density and body size in
      animal assemblages has been debated because of known biases and ambiguities in
      the published data and data handling. Using new comprehensive data sets from two
      geographically separated stream communities that encompass 448 and 260
      invertebrate taxa with a wide range of body sizes, we show that an inverse
      proportionality between density and body size is a consistent feature in these
      communities. The scaling across taxa is not statistically different between the
      two systems, indicating a convergent pattern of communities. Variation in the
      regression slope among different taxonomic groups indicates that these
      communities are not governed universally by a single ecological or energetic
      rule.

PMID- 10968793
TI  - Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha
      ubiquitination.
AB  - Epithelia of the vertebrate intestinal tract characteristically maintain an
      inflammatory hyporesponsiveness toward the lumenal prokaryotic microflora. We
      report the identification of enteric organisms (nonvirulent Salmonella strains)
      whose direct interaction with model human epithelia attenuate synthesis of
      inflammatory effector molecules elicited by diverse proinflammatory stimuli. This
      immunosuppressive effect involves inhibition of the inhibitor kappaB/nuclear
      factor kappaB (IkappaB/NF-kappaB) pathway by blockade of IkappaB-alpha
      degradation, which prevents subsequent nuclear translocation of active NF-kappaB
      dimer. Although phosphorylation of IkappaB-alpha occurs, subsequent
      polyubiquitination necessary for regulated IkappaB-alpha degradation is
      completely abrogated. These data suggest that prokaryotic determinants could be
      responsible for the unique tolerance of the gastrointestinal mucosa to
      proinflammatory stimuli.

PMID- 10968794
TI  - Generation of G-to-A and C-to-U changes in HIV-1 transcripts by RNA editing.
AB  - RNA editing involves posttranscriptional alterations of messenger RNA (mRNA)
      sequences modifying the information content encoded by the genetic message. Here,
      it is shown that, in chronically infected H9 cells, human immunodeficiency virus
      type 1 (HIV-1) mRNAs undergo guanine-to-adenine (G-to-A) and cytosine-to-uracil
      (C-to-U) changes. G-to-A modification in the untranslated region of exon 1 was
      present only in spliced HIV-1 mRNAs. The creation of stop codons in HIV-1 mRNAs
      may function to control the translation of viral proteins, such as viral protein
      R, that are involved in the regulation of HIV-1 expression and the survival of
      chronically infected cells.

PMID- 10968795
TI  - Extension of life-span with superoxide dismutase/catalase mimetics.
AB  - We tested the theory that reactive oxygen species cause aging. We augmented the
      natural antioxidant systems of Caenorhabditis elegans with small synthetic
      superoxide dismutase/catalase mimetics. Treatment of wild-type worms increased
      their mean life-span by a mean of 44 percent, and treatment of prematurely aging
      worms resulted in normalization of their life-span (a 67 percent increase). It
      appears that oxidative stress is a major determinant of life-span and that it can
      be counteracted by pharmacological intervention.

PMID- 10968796
TI  - Responses of vomeronasal neurons to natural stimuli.
AB  - The vomeronasal organ (VNO) of mammals plays an essential role in the detection
      of pheromones. We obtained simultaneous recordings of action potentials from
      large subsets of VNO neurons. These cells responded to components of urine by
      increasing their firing rate. This chemosensory activation required phospholipase
      C function. Unlike most other sensory neurons, VNO neurons did not adapt under
      prolonged stimulus exposure. The full time course of the VNO spiking response is
      captured by a simple quantitative model of ligand binding. Many individual VNO
      neurons were strongly selective for either male or female mouse urine, with the
      effective concentrations differing as much as a thousandfold. These results
      establish a framework for understanding sensory coding in the vomeronasal system.

PMID- 10968797
TI  - Chemotherapy for advanced colorectal cancer.

PMID- 10968798
TI  - How to manage the first episode of schizophrenia.

PMID- 10968799
TI  - Obesity surgery-another unmet need.

PMID- 10968800
TI  - The future of research into rotavirus vaccine.

PMID- 10968802
TI  - US government to fund human stem cell research.

PMID- 10968801
TI  - A fair way of donating hearts for transplantation.

PMID- 10968803
TI  - UK government approves limited cloning of human embryos.

PMID- 10968804
TI  - Suicides in Japan reach a record high.

PMID- 10968806
TI  - In brief

PMID- 10968805
TI  - French health costs rising rapidly.

PMID- 10968807
TI  - Siamese twins to be separated against parents' will.

PMID- 10968808
TI  - More "cot deaths" occur in day care than at home

PMID- 10968810
TI  - New cytokine treatment for inflammatory bowel disease.

PMID- 10968809
TI  - Baby's penis reattached after botched circumcision.

PMID- 10968811
TI  - Dutch waiting lists increase despite 36m (sterling pounds) campaign.

PMID- 10968812
TI  - Palliative chemotherapy for advanced colorectal cancer: systematic review and
      meta-analysis. Colorectal Cancer Collaborative Group.
AB  - OBJECTIVES: To determine the benefits and harms of palliative chemotherapy in
      patients with locally advanced or metastatic colorectal cancer and to compare the
      outcomes for elderly and younger patients. DESIGN: Meta-analysis of individual
      patient data and published summary statistics from trials for which individual
      patient data could not be obtained from the investigators. STUDIES: All
      randomised controlled trials comparing palliative chemotherapy with supportive
      care in patients with advanced colorectal cancer that were identified by
      computerised and hand searches of the literature, scanning references, and
      contacting investigators. MAIN OUTCOME MEASURES: Survival, disease progression,
      quality of life, and toxicity. RESULTS: 13 randomised controlled trials including
      a total of 1365 patients met the inclusion criteria. Meta-analysis of seven
      trials that provided individual patient data (866 patients) showed that
      palliative chemotherapy was associated with a 35% reduction in the risk of death
      (95% confidence interval 24% to 44%). This translates into an absolute
      improvement in survival of 16% at both six and 12 months and an improvement in
      median survival of 3.7 months. No age related differences were found in the
      effectiveness of chemotherapy, but elderly patients were under represented in
      trials. The overall quality of evidence relating to treatment toxicity, symptom
      control, and quality of life was poor. CONCLUSIONS: Chemotherapy is effective in
      prolonging time to disease progression and survival in patients with advanced
      colorectal cancer. The survival benefit may be underestimated in this analysis as
      some patients in the control arms received chemotherapy.

PMID- 10968813
TI  - Comparison of St John's wort and imipramine for treating depression: randomised
      controlled trial.
AB  - OBJECTIVES: To compare the efficacy and tolerability of Hypericum perforatum (St
      John's wort extract) with imipramine in patients with mild to moderate
      depression. DESIGN: Randomised, multicentre, double blind, parallel group trial.
      SETTING: 40 outpatient clinics in Germany. PARTICIPANTS: 324 outpatients with
      mild to moderate depression. INTERVENTION: 75 mg imipramine twice daily or 250 mg
      hypericum extract ZE 117 twice daily for 6 weeks. MAIN OUTCOME MEASURES: Hamilton
      depression rating scale, clinical global impression scale, and patient's global
      impression scale. RESULTS: Among the 157 participants taking hypericum mean
      scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00
      at end point; among the 167 participants taking imipramine they fell from 22.1 to
      12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for
      the hypericum group and 2.42 for the imipramine group. On the 7 point self
      assessments of global improvement completed by participants (score of 1
      indicating "very much improved" and 7 indicating "very much deteriorated") mean
      scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of
      the differences between treatment groups were significant. However, the mean
      score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the
      hypericum group and 4.26 in the imipramine group) indicated a significant
      advantage for hypericum relative to imipramine. Mean scores on the 5 point scale
      used by participants to assess tolerability (score of 1 indicating excellent
      tolerability and 5 indicating very poor tolerability) were better for hypericum
      (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%)
      participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%)
      participants taking hypericum withdrew because of adverse events compared with 26
      (16%) taking imipramine. CONCLUSIONS: This Hypericum perforatum extract is
      therapeutically equivalent to imipramine in treating mild to moderate depression,
      but patients tolerate hypericum better.

PMID- 10968815
TI  - Birth characteristics of women who develop gestational diabetes: population based
      study.

PMID- 10968814
TI  - Effect of receiving a heart transplant: analysis of a national cohort entered on
      to a waiting list, stratified by heart failure severity. Comparative Outcome and
      Clinical Profiles in Transplantation (COCPIT) Study Group.
AB  - OBJECTIVE: To determine whether there is a survival benefit associated with
      cardiac transplantation in Germany. DESIGN: Prospective observational cohort
      study. SETTING: All 889 adult patients listed for a first heart transplant in
      Germany in 1997. MAIN OUTCOME MEASURE: Mortality, stratified by heart failure
      severity. RESULTS: Within 1 year after listing, patients with a predicted high
      risk had the highest global death rate (51% v 32% and 29% for medium and low risk
      patients respectively; P<0.0001), had the highest risk of dying on the waiting
      list (32% v 20% and 20%; P=0.0003), and were more likely to receive a transplant
      (48% v 45% and 41%; P=0.01). Differences between the risk groups in outcome after
      transplantation did not reach significance (P=0.2). Transplantation was not
      associated with a reduction in mortality risk for the total cohort, but it did
      provide a survival benefit for the high risk group. CONCLUSION: Cardiac
      transplantation in Germany is currently associated with a survival benefit only
      in patients with a predicted high risk of dying on the waiting list. Patients
      with a predicted low or medium risk have no reduction in mortality risk
      associated with transplantation; they should be managed with organ saving
      approaches rather than transplantation.

PMID- 10968817
TI  - Email submissions from outside the united kingdom

PMID- 10968818
TI  - Identifying patients with ischaemic heart disease in general practice: cross
      sectional study of paper and computerised medical records.
AB  - OBJECTIVES: To identify patients with ischaemic heart disease by using a practice
      computer and to estimate the work required to do so. DESIGN: Cross sectional
      study. Data from the notes and from the computer records of 1680 patients were
      used to build a database. This was used to compare different methods of
      identifying patients with ischaemic heart disease. SETTING: 11 general practices
      in the Battersea primary care group in south London. SUBJECTS: 1 in 40 random
      sample of patients aged 45 or older. MAIN OUTCOME MEASURES: Numbers of patients
      identified with ischaemic heart disease. RESULTS: The combination of the Read
      code for ischaemic heart disease (G3) and a prescription for a nitrate had a 73%
      sensitivity and a yield (100/positive predictive value) of one case of ischaemic
      heart disease for every 1.2 sets of notes reviewed. By searching the records of
      patients also receiving aspirin, atenolol, digoxin, or a statin, the sensitivity
      was increased to 96% but the yield fell to one in three. CONCLUSION: Although
      commonly used to identify cases, a computer search for G3 code or nitrate missed
      almost 30% of patients with ischaemic heart disease. A substantially higher
      percentage of patients can be identified by adding other drugs to the search
      strategy.

PMID- 10968816
TI  - Drug points: prolonged cholestasis associated with irbesartan.

PMID- 10968819
TI  - The power of prayer

PMID- 10968821
TI  - Experience not required

PMID- 10968820
TI  - Clinical governance in primary care. Improving quality in the changing world of
      primary care.

PMID- 10968823
TI  - Medicine as a career

PMID- 10968824
TI  - ABC of oral health. Dental emergencies.

PMID- 10968822
TI  - Recent advances: palliative care.

PMID- 10968825
TI  - Role of private sector in United Kingdom healthcare system.

PMID- 10968826
TI  - Evaluating "payback" on biomedical research. Biomedical funding decisions should
      be audited.

PMID- 10968827
TI  - Pragmatic approach is effective in evidence based health care.

PMID- 10968828
TI  - Evidence should be accessible as well as relevant.

PMID- 10968829
TI  - Costs are as important as outcomes.

PMID- 10968830
TI  - Breast cancer screening. Screening has to be combined with good surgical and
      oncological services.

PMID- 10968831
TI  - Non-steroidal anti-inflammatory drugs. Article was inconsistent.

PMID- 10968832
TI  - Generalisations on benefits of aspirin are dangerous.

PMID- 10968833
TI  - Detecting tuberculosis in new arrivals to UK. Occupational health screening of
      doctors must be improved.

PMID- 10968834
TI  - Detecting tuberculosis in new arrivals to UK. Screening is of doubtful value.

PMID- 10968835
TI  - Detecting tuberculosis in new arrivals to UK. Failure to register with a general
      practice compounds the problem.

PMID- 10968836
TI  - Ulcerative colitis should be investigated differently in children.

PMID- 10968837
TI  - Ending genital mutilation. Women in Africa have many other problems besides
      genital mutilation.

PMID- 10968838
TI  - Standard GP search strategies miss many patients with heart disease

PMID- 10968839
TI  - Risk of gestational diabetes increases in women whose mothers had diabetes during
      pregnancy

PMID- 10968841
TI  - Working in barbados

PMID- 10968840
TI  - Lack of collaboration between UK's private and public health sectors is a lost
      opportunity

PMID- 10968842
TI  - Focus on...fiberoptic colonoscope.

PMID- 10968843
TI  - Role of Doppler US in acute peptic ulcer hemorrhage: can it predict failure of
      endoscopic therapy?
AB  - BACKGROUND: Recurrent bleeding after successful primary endoscopic hemostasis of
      acutely bleeding ulcers is a significant problem. This study evaluates endoscopic
      Doppler ultrasound (US) in assessing risk of recurrent bleeding in patients
      presenting with acute peptic ulcer hemorrhage. METHODS: In this prospective,
      double-blind, nonrandomized trial, patients were enrolled from a single academic
      institution. Only patients with endoscopically confirmed gastric, duodenal,
      pyloric, or anastomotic ulcers were enrolled. The therapeutic endoscopist was
      blinded to the Doppler US signal from the ulcer and based treatment decisions on
      standard guidelines. A 16 MHz pulsed-wave, linear scanning, US probe was used
      through the accessory channel of an endoscope to assess for the presence of a
      Doppler signal. RESULTS: Fifty-two of 139 screened patients entered the trial (55
      Doppler sessions). Endoscopic therapy was performed in 42% (30-day recurrent
      bleeding rate of 17%). Ulcers that remained persistently Doppler positive
      immediately after endoscopic therapy had a significantly higher rate of recurrent
      bleeding than ulcers where the Doppler signal was abolished: 100% versus 11% (p =
      0.003). There were no bleeding-related deaths. CONCLUSIONS: A persistently
      positive Doppler US signal appears to be a marker of inadequate endoscopic
      therapy in patients with acutely bleeding peptic ulcers.

PMID- 10968844
TI  - Clinical outcome of endoscopic mucosal resection for superficial GI lesions and
      the role of high-frequency US probe sonography in an American population.
AB  - BACKGROUND: Endoscopic mucosal resection, a major advance in endoscopy, provides
      an endoscopic option for management of focal and superficial lesions of the
      gastrointestinal tract. Although popular in the Orient due to the high incidence
      of superficial neoplasia, there are scant data on its use in the United States.
      Our aim was to assess the efficacy and safety of endoscopic mucosal resection in
      our patient population and evaluate whether high-frequency ultrasound (US) probe
      sonography provides useful information relative to the procedure. METHODS:
      Endoscopic mucosal resection was performed in 32 of 33 patients referred for
      endoscopic management of superficial neoplastic or submucosal lesions. High
      frequency US probe sonography was performed with a 20 MHz US probe. Endoscopic
      mucosal resection was performed after submucosal saline solution injection with
      the strip biopsy technique. RESULTS: Thirty-two superficial lesions were
      resected. Of 24 epithelial lesions resected, 22 were intramucosal and 2 had early
      submucosal invasion (SM1); the 2 patients with the latter 2 lesions were poor
      candidates for surgery. Depth of penetration of 25 of 26 lesions scanned was
      accurately predicted by high-frequency US probe sonography. Eight lesions raised
      from the submucosa. Minor complications were limited to the colon. Of the 7
      patients with carcinomas, 6 had no evidence of recurrence at a mean follow-up of
      12 months; 1 died of a second primary cancer. CONCLUSIONS: Endoscopic mucosal
      resection provided definitive therapy for 24 early-stage neoplastic lesions and
      provided a diagnosis in the remaining 8. In our study, the technique proved to be
      safe with only three minor complications noted. High-frequency US probe
      sonography accurately delineated the depth of penetration of all lesions scanned,
      therefore making it an ideal imaging modality for selecting patients who may
      benefit from endoscopic mucosal resection.

PMID- 10968846
TI  - Is the diagnostic yield of upper GI endoscopy improved by the use of explicit
      panel-based appropriateness criteria?
AB  - BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI)
      endoscopy is important to improve quality of care while at the same time
      containing costs. This study explored whether detailed explicit appropriateness
      criteria significantly improve the diagnostic yield of upper GI endoscopy.
      METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1
      university hospital, 2 district hospitals, 3 gastroenterology practices) were
      prospectively included over a 6-month period. After controlling for disease
      presentation and patient characteristics, the relationship between the
      appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria
      developed by the RAND/UCLA panel method, and the presence of relevant endoscopic
      lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57%
      men) were included. Analysis was restricted to the 1681 patients referred for
      diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were
      judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit
      criteria. No cancer was found in upper GI endoscopies judged to be inappropriate.
      Upper GI endoscopies judged appropriate or uncertain yielded significantly more
      relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio
      2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper
      GI endoscopy was significantly influenced by appropriateness, patient gender and
      age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed
      for appropriate indications resulted in detecting significantly more clinically
      relevant lesions than did those performed for inappropriate indications. In
      addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged
      to be inappropriate. The use of such criteria improves patient selection for
      upper GI endoscopy and can thus contribute to efforts aimed at enhancing the
      quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

PMID- 10968845
TI  - Endoscopic mucosal resection for lesions with endoscopic features suggestive of
      malignancy and high-grade dysplasia within Barrett's esophagus.
AB  - BACKGROUND: Endoscopic mucosal resection has been used in the treatment of
      superficial squamous cell cancers and gastric malignancies. Our aim was to
      determine whether endoscopic mucosal resection can be used in the diagnosis of
      lesions within Barrett's esophagus whose endoscopic appearances raise suspicion
      of carcinoma or high-grade dysplasia. METHODS: Twenty-five patients with such
      lesions within Barrett's esophagus underwent endoscopic mucosal resection for
      diagnostic and therapeutic purposes. All patients underwent endoscopic ultrasound
      to determine the feasibility of endoscopic resection. Only lesions found to be
      uT0 or uT1 underwent EMR. The lift and cut technique was used in 23 patients and
      a variceal ligating device was used on 2 patients. RESULTS: Endoscopic mucosal
      resection was performed because of a nodule or polyp within Barrett's esophagus
      in 11 patients (44%) and suspected superficial cancer or high-grade dysplasia in
      14 patients (56%). Endoscopic mucosal resection diagnosed superficial
      adenocarcinoma in 13 patients (52%) and high-grade dysplasia in 4 (16%); it
      confirmed lesions in 8 patients (40%) to be of lower neoplastic risk. No
      complications occurred due to the procedure itself. CONCLUSIONS: Endoscopic
      mucosal resection is a technique with low morbidity and mortality. It has led to
      a change in diagnosis in patients with Barrett's esophagus and lesions with
      endoscopic features that suggest neoplasia. Its major advantages include
      simplicity and retrieval of the specimen en bloc.

PMID- 10968847
TI  - The tissue effect of argon plasma coagulation on esophageal and gastric mucosa.
AB  - BACKGROUND: Argon plasma coagulation is a diathermy-based non-contact therapeutic
      endoscopic modality that may have a lower risk of perforation than other tissue
      ablation techniques. METHODS: Its effect was studied on three fresh esophageal
      and three fresh gastric resection specimens using power settings from 40 to 99
      Watts at 90 degrees, with 1 mm separation using pulse durations of 1 and 3
      seconds. A scoring system for depth of tissue damage was created and samples were
      analyzed blindly by a gastrointestinal histopathologist. RESULTS: There was
      significantly greater damage to gastric tissue using a 3-second (compared with 1
      second) pulse (p = 0.003) and marginally significantly greater damage to
      esophageal tissue using the 3-second pulse (p = 0.053). Tissue damage was related
      to power setting for gastric (p = 0.031) but not for esophageal tissue (p = 0.
      065). Only 1 of 42 esophageal samples and 2 of 42 gastric samples examined showed
      damage extending into the muscularis propria. CONCLUSIONS: Deep tissue damage
      that could lead to perforation was rare with argon plasma coagulation. The depth
      of gastric mucosal damage increased with increased pulse duration and increasing
      power settings, and, although the depth of esophageal mucosal damage was
      marginally related to pulse duration, it was not related to the power setting.
      (Gastrointest Endosc 2000;52:342-5).

PMID- 10968848
TI  - A novel tableted purgative for colonoscopic preparation: efficacy and safety
      comparisons with Colyte and Fleet Phospho-Soda.
AB  - BACKGROUND: Currently available aqueous purgatives used before colonoscopy are
      poorly tolerated. We designed a tableted sodium phosphate purge that we believe
      will yield much greater patient acceptance. METHODS: A total of 305 outpatients
      undergoing routine diagnostic colonoscopy were randomized to one of three
      preparation groups: Colyte (100 patients), Fleet Phospho-Soda (106 patients), or
      sodium phosphate tablets (99 patients). Endoscopists were blinded to the type of
      preparation administered and answered a questionnaire regarding preparation
      quality. Patients answered a questionnaire designed to analyze tolerability.
      Adverse events were closely followed and recorded. RESULTS: There were no
      significant differences in quality of preparation across the groups (80%
      excellent or good, 4% repreparation). Although hypocalcemia (4 of 71),
      hypokalemia (18 of 68), and hyperphosphatemia (39 of 69) were observed in
      patients receiving the tablets, no adverse events occurred. Patients preferred
      taking the tablets over Colyte and Fleet Phospho-Soda. CONCLUSION: The evaluation
      of a novel delivery system of a sodium phosphate purge is described. Intended for
      use before colonoscopy, it circumvents the poor taste and excessive volume of
      ingestion that are aversive to patients. The tableted purgative is equally
      effective, safe, and greatly preferred over the existing aqueous preparations.
      This may improve patient compliance with recommendations for screening
      colonoscopy.

PMID- 10968849
TI  - KTP laser therapy for bleeding from chronic radiation proctopathy.
AB  - BACKGROUND: Endoscopic laser photocoagulation is commonly used to treat bleeding
      from the neovascular lesions of chronic radiation proctopathy. The KTP laser is
      an Nd/YAG-driven unit that emits light with a wavelength of 532 nm. This
      wavelength of energy is absorbed by hemoglobin and penetrates tissue to a depth
      of only 1 to 2 mm. METHODS: Twenty-three patients were treated with KTP laser and
      followed for a median of 29 months (range 5 to 51 months); 21 had received
      radiation for prostate cancer and 2 for uterine cancer. The median age was 77
      years (range 68 to 87 years). A median of 2 sessions (range 1 to 5 sessions) was
      performed using 4 to 10 Watts of power and a median energy of 816 Joules per
      session (range 204 to 2430 Joules). RESULTS: After treatment there was a
      significant reduction in the frequency (p = 0.0005) of bleeding, increase in
      hematocrit level (p < 0.0001), improvement in activities of daily life (p =
      0.01), and a reduction in use of health care resources (p < 0.0001). There was a
      trend toward decreased use of iron supplements (11 to 4 patients) and
      transfusions (4 to 0 patients). Two patients (9%) developed rectal ulcers after
      treatment. CONCLUSIONS: KTP laser photocoagulation is a safe and effective
      therapy for bleeding from chronic radiation proctopathy that improves activities
      of daily living and reduces use of health care resources.

PMID- 10968850
TI  - Significance of small distal adenoma for detection of proximal neoplasms in the
      colorectum.
AB  - BACKGROUND: The significance of the small distal tubular adenoma detected by
      sigmoidoscopy as a predictor of proximal neoplasm remains controversial. The aim
      of this study was to examine the prevalence of proximal neoplasms in patients
      with and without distal neoplasms. METHODS: This is a retrospective study of 3131
      asymptomatic middle-aged men who underwent total colonoscopy. For 812 men with
      colorectal neoplasms characteristics of the identified neoplasms were determined.
      RESULTS: The prevalence of proximal neoplasms in patients with small distal
      tubular adenoma was 20% (92 of 461), whereas the prevalence of proximal neoplasms
      in patients without distal neoplasms was 11.5% (301 of 2620). The prevalence of
      advanced proximal neoplasms in patients with small distal tubular adenoma and
      without distal neoplasm was 1.3% and 0.8%, respectively. In the 29 patients with
      advanced proximal neoplasms, only 6 (21%) had a small distal tubular adenoma.
      CONCLUSIONS: The presence of small distal tubular adenomas may provide a clue to
      the presence of small proximal tubular adenomas. However, the majority of
      advanced proximal neoplasms (79%) do not have a synchronous small distal tubular
      adenoma. (Gastrointest Endosc 2000;52:358-61).

PMID- 10968851
TI  - Routine droperidol pre-medication improves sedation for ERCP.
AB  - BACKGROUND: Pre-medication with droperidol has been used to improve sedation
      during endoscopy, especially in patients with a history of alcohol or narcotic
      abuse. We studied whether routine use of droperidol pre-endoscopic retrograde
      cholangiopancreatography (ERCP) could improve patient and physician satisfaction
      with sedation. METHODS: Sixty-seven patients undergoing routine ERCP were
      enrolled in this double-blind placebo-controlled study. Patients were given
      either parenteral normal saline solution or 5 mg of droperidol 15 minutes before
      the procedure. After the ERCP, several parameters of procedural sedation were
      scored on an ordinal scale by the endoscopist, the endoscopy nurse, and the
      recovered patient. In addition, a follow-up telephone call was made to the
      patient after 24 hours. RESULTS: The mean procedural room time was similar in the
      two groups. Nearly 25% less meperidine and diazepam was used in the droperidol
      treated patients, making the overall medication cost similar in both groups. The
      mean recovery room time was 113 minutes for the placebo group and 106 minutes for
      the droperidol group. Droperidol premedication significantly decreased post
      procedure nausea and vomiting, reduced gagging at intubation, and decreased
      retching during the procedure. Droperidol also improved physician (p = 0.001),
      nurse (p = 0.001), and patient (p = 0.0001) impressions of overall sedation and
      decreased the need for physical restraint during the procedure. Droperidol
      significantly increased the number of patients with no memory of the procedure.
      CONCLUSION: Droperidol improved overall patient, physician, and nurse
      satisfaction with sedation during ERCP. It also reduced post-ERCP nausea and
      vomiting without increasing recovery time or medication cost. Droperidol is
      recommended for routine pre-ERCP sedation. (Gastrointest Endosc 2000;52:362-6).

PMID- 10968852
TI  - EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma.
AB  - BACKGROUND: Preoperative diagnosis of pancreatic adenocarcinoma can be difficult.
      Computed tomography (CT) is the standard, noninvasive imaging method for
      evaluation of suspected pancreatic adenocarcinoma, but it has limited sensitivity
      for diagnosis, local staging, and metastases. Endoscopic ultrasound (EUS) and
      fluoro-deoxyglucose/positron emission tomography (FDG-PET) are imaging methods
      that may improve diagnostic accuracy. METHODS: Thirty-five patients with presumed
      resectable pancreatic adenocarcinoma were prospectively evaluated with helical
      CT, EUS, and FDG-PET. RESULTS: Sensitivity for the detection of pancreatic cancer
      was higher for EUS (93%) and FDG-PET (87%) than for CT (53%). EUS was more
      sensitive than CT for local vascular invasion of the portal and superior
      mesenteric veins. EUS diagnosis of vascular invasion was associated with poor
      outcome after surgery. EUS-guided, fine-needle aspiration allowed tissue
      diagnosis in 14 of 21 attempts (67%). FDG-PET diagnosed 7 of 9 cases of proven
      metastatic disease, 4 of which were missed by CT. Two of three metastatic liver
      lesions suspected by CT were indeterminate for metastases. FDG-PET confirmed
      metastases. CONCLUSIONS: EUS and PET improve diagnostic capability in pancreatic
      adenocarcinoma. EUS is useful in determining local vascular invasion and
      obtaining tissue diagnosis. FDG-PET is useful in identifying metastatic disease.
      Both techniques are more sensitive than helical CT for identification of the
      primary tumor. (Gastrointest Endosc 2000;52:367-71).

PMID- 10968853
TI  - A new strategy to predict the neoplastic polyps of the gallbladder based on a
      scoring system using EUS.
AB  - BACKGROUND: A new method to predict neoplastic polyps of the gallbladder using a
      scoring system based on five endoscopic ultrasonography (EUS) variables is
      presented. METHODS: EUS data from patients with gallbladder polyps who were to
      undergo cholecystectomy were used for the construction of an EUS scoring system
      in polyps between 5 and 15 mm in diameter (reference group). The EUS scoring
      system developed from those patients was applied to other patients (validation
      group). RESULTS: In the reference group, size was the most significant predictor
      of neoplastic polyp. All polyps 5 mm or less in diameter were non-neoplastic and
      94% of polyps of greater than 15 mm were neoplastic in the reference group. For
      polyps between 5 and 15 mm in diameter, the area under the receiver-operating
      characteristic curves (ROC) plots for the endoscopic scoring system was
      significantly greater than that under the ROC plots for polyp size alone (p <
      0.01). In the validation group, the risk of neoplastic polyp was significantly
      higher for polyps with a score of 6 or greater compared with those with a score
      of less than 6 (p < 0.01). CONCLUSIONS: Our data show that a score based on five
      EUS variables identifies those patients at risk of neoplasia when polyps are
      between 5 and 15 mm in diameter. (Gastrointest Endosc 2000;52:372-9).

PMID- 10968854
TI  - Detection of telomerase activity in biopsy specimens for diagnosis of biliary
      tract cancers.
AB  - BACKGROUND: Telomerase activity is detectable in more than 85% of primary
      cancers. We determined telomerase activity in biopsy specimens obtained from
      biliary tract cancers to evaluate the clinical application of telomerase activity
      detection in combination with p53 immunostaining and routine histologic
      examination. METHODS: Biopsy specimens obtained during percutaneous transhepatic
      cholangioscopy from 13 patients with cholangiocarcinoma, 3 patients with
      gallbladder carcinoma, and 4 patients with intrahepatic bile duct stones were
      evaluated by routine histologic examination, p53 immunostaining, and telomerase
      activity. Semiquantitative determination of telomerase activity was performed
      using a fluorescence-based telomeric repeat amplification protocol. RESULTS:
      Thirteen of 16 specimens of malignant tissue had detectable telomerase activity,
      whereas no specimen of nonmalignant tissue had detectable telomerase activity. A
      p53 overexpression was recognized by immunostaining in 9 of 16 samples with
      cancers. Combining both telomerase activity and p53 overexpression resulted in
      the detection of all cancer with a sensitivity of 100%. There were no false
      positive results by either modality (specificity 100%). CONCLUSIONS: The
      detection of telomerase activity in biopsy specimens and p53 overexpression in
      combination with routine histologic examination may improve the diagnosis of
      biliary tract cancers. (Gastrointest Endosc 2000;52:380-6).

PMID- 10968856
TI  - Colonoscopic findings in an adult patient with Henoch-Schonlein purpura.

PMID- 10968855
TI  - A sphincterotome-based technique for selective transpapillary common bile duct
      cannulation.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) requires
      selective cannulation of the common bile duct and pancreatic duct. Selective
      common bile and pancreatic duct cannulation with standard techniques can be
      achieved in most but not all cases even in experienced centers. To facilitate
      selective cannulation, sphincterotomes can be used. METHODS: A prospective
      randomized study aimed at selective deep cannulation of the common bile and
      pancreatic ducts comparing different ERCP procedures was performed. One hundred
      patients were randomly assigned to undergo cannulation with a standard catheter
      or with a guidewire sphincterotome (GS) without guidewire. RESULTS: The primary
      success rate of selective common bile duct cannulation was significantly higher
      in the GS group (84%) as compared with the standard catheter group (62%) (p =
      0.023). In patients with primary standard catheter failure, selective common bile
      duct cannulation was possible in 16 patients using a GS which increased the total
      success rate in the standard catheter group to 94% (p < 0.001). In GS failures
      selective common bile duct cannulation was possible in two patients using a
      standard catheter and increased the total success rate from 84% to 88%. The
      frequency of postinterventional pancreatitis did not differ significantly between
      the two groups. CONCLUSIONS: ERCP using a GS without guidewire has a
      significantly higher primary success rate for selective common bile duct
      cannulation then ERCP using a standard catheter. The use of a GS should be
      considered to optimize selective cannulation of the common bile duct before
      resorting to precut techniques.

PMID- 10968857
TI  - Metastatic malignant melanoma involving the colon.

PMID- 10968858
TI  - Actively bleeding gastric varix.

PMID- 10968859
TI  - Light-induced autofluorescence spectroscopy for tissue diagnosis of GI lesions.
AB  - BACKGROUND: The present article describes light-induced autofluorescence
      spectroscopy using violet-blue excitation light for endoscopic in vivo
      measurements in the upper GI tract. The spectra of normal mucosa, cancer, and
      dysplastic lesions of the esophagus and stomach are presented and compared.
      METHODS: Over 120 spectra were obtained in 11 patients of normal mucosa and
      malignant lesions in the esophagus and stomach during routine endoscopy. A
      special light source capable of delivering either white or violet-blue light was
      used for the excitation of tissue auto-fluorescence via the endoscope. Endogenous
      fluorescence spectra emitted by the tissue were collected with a fiberoptic probe
      and analyzed with a spectrograph. After spectrographic measurements biopsies were
      taken for definitive classification of histopathologic status. RESULTS: As
      compared with normal mucosa, (pre) cancerous lesions were associated with special
      changes in the emitted fluorescence spectra. The spectrographic records were
      influenced by the intensity of the illumination and on the position of the probe
      (distance and angle). CONCLUSION: Fluorescence spectroscopy with a slightly
      modified conventional light source might be useful for the endoscopic detection
      of dysplasia and early-stage carcinoma in the upper GI tract. Prospective trials
      need to determine the sensitivity and specificity of this new method.

PMID- 10968860
TI  - Improved model for teaching interventional EUS.
AB  - BACKGROUND: A swine model was previously developed for teaching endoscopic
      ultrasound (EUS). The purpose of this study was to improve this model and develop
      a method for creating focal lesions for EUS imaging and intervention. METHODS:
      Experiments were performed in farm pigs (Sus scrofa) under general anesthesia.
      Under real-time EUS guidance attempts were made to create a submucosal lesion and
      a focal mediastinal lesion, to perform EUS-guided fine-needle aspiration of the
      pancreas, and to confirm the site of injection during "sham" EUS-guided celiac
      block. RESULTS: A hypoechoic, submucosal mass was created in the stomach, which
      was then imaged by EUS and punctured trans-gastrically. Injection of saline
      solution in the mediastinum created a pseudo-mediastinal lymph node. A needle was
      then advanced trans-esophageally into the mediastinum to mimic EUS-guided fine
      needle aspiration of a mediastinal lymph node. Abdominal exploration of the pigs
      after euthanasia confirmed injection of the sham celiac block around the celiac
      ganglion. CONCLUSION: The swine model is not only useful for teaching normal EUS
      anatomy, but it may be a useful model for teaching EUS-guided intervention.

PMID- 10968861
TI  - A new endoscopic technique for the removal of gastric phytobezoars.
AB  - BACKGROUND: There is no standardized method for the evacuation of gastric
      phytobezoars. Prior endoscopic attempts have used injected cellulase and various
      devices to disrupt bezoars. The efficacy of directed, large-channel suction using
      an endoscope for the removal of large gastric phytobezoars is the subject of this
      study. METHODS: Three consecutive patients with large gastric bezoars were
      examined. Phytobezoar removal using a standard endoscope (GIF-100, Olympus) was
      attempted but unsuccessful. Each phytobezoar was successfully evacuated by
      directed suction through an endoscope with a large-diameter accessory channel
      (GIF-XT30, Olympus). Each patient was followed up for bezoar recurrence. RESULTS:
      Rapid, complete bezoar evacuation was achieved at one session in all patients.
      Aspirated volumes were 500, 700, and 1000 mL. There were no procedure-related
      complications. CONCLUSIONS: Endoscopic suction removal of gastric phytobezoars
      using a large-channel endoscope is efficacious and safe. Coupling directed
      endoscopic suction with other endoscopic techniques might be efficacious for
      removal of more complex bezoars.

PMID- 10968862
TI  - A case of mucin-hypersecreting intrahepatic bile duct tumor associated with
      pancreatic intraductal papillary mucinous tumor.

PMID- 10968864
TI  - Pancreaticopleural fistula in chronic pancreatitis: resolution with endoscopic
      therapy.

PMID- 10968863
TI  - Successful percutaneous treatment of infected necrosis of the body of the
      pancreas associated with segmental disruption of the main pancreatic duct.

PMID- 10968865
TI  - A case of pancreatic carcinoma diagnosed by intraductal US after lithotripsy for
      pancreatolithiasis.

PMID- 10968866
TI  - Topical formalin therapy by means of an endoscopic applicator for control of
      ileoanal pouch ulcer bleeding.

PMID- 10968867
TI  - Laparoscopic removal of an ingested foreign body and repair of colonic
      perforation.

PMID- 10968868
TI  - Endoscopic resection of adenocarcinoma arising in a tongue of Barrett's
      esophagus.

PMID- 10968869
TI  - Mucous membrane pemphigoid presenting with isolated esophageal involvement: a
      case report.

PMID- 10968870
TI  - Endoscopic hemostasis of hemorrhage from esophageal bullous pemphigoid.

PMID- 10968871
TI  - Brunner's gland hamartoma presenting as a large duodenal polyp.

PMID- 10968872
TI  - Successful treatment of a benign anastomotic stricture despite stent migration.

PMID- 10968873
TI  - Do we need more technology to reduce recurrence of bleeding from ulcers?

PMID- 10968874
TI  - Endoscopic mucosal resection: (not) made in the USA (so commonly). A dissection
      of the definition, technique, use, and controversies.

PMID- 10968875
TI  - Continuing education in endoscopy: live courses or video format?

PMID- 10968876
TI  - The usefulness of endoscopy in diagnosing celiac disease in Greece.

PMID- 10968877
TI  - Celiac disease detected at endoscopy.

PMID- 10968878
TI  - Anesthesia facilitates the extraction of rectal foreign bodies.

PMID- 10968879
TI  - Cytomegalovirus infection in children with Down syndrome in a day-care center in
      Brazil.
AB  - This study evaluates the transmission of CMV infection in 120 children aged 1 to
      15 years with Down syndrome who attended a day-care center for handicapped
      children in Sao Paulo, Brazil. A blood sample was obtained from each children at
      the beginning of the study for detection of IgG and IgM cytomegalovirus (CMV)
      antibodies by an immunofluorescence assay. Samples of saliva and urine were
      obtained every 3 months from the children with CMV antibodies to detect shedding
      of the virus by culture in human foreskin fibroblasts, by detection of pp65 CMV
      antigen and by a nested PCR assay. The prevalence of anti CMV-IgG antibodies was
      76.6% (92/120), and IgM anti-CMV antibodies were detected in 13% (12/92) of the
      seropositive children. During the first viral evaluation, CMV was detected in the
      urine and/or saliva in 39/90 (43.3%) of the seropositive children. In the second
      and third evaluations, CMV was detected in 41/89 (46%) and in 35/89 (39.3%)
      children, respectively. Detection of CMV was shown both in urine and saliva in
      28/39 (71.8%), 19/41(46.3%) and 20/35 (57.1%) of the children excreting the
      virus, respectively. Additionally, in 3(3/4)9 (67.4%) of the excreters CMV could
      be demonstrated in urine or saliva in at least two out of the three virological
      evaluations carried out sequentially in a six month period. Of the 28 initially
      seronegative children, 26 were re-examined for anti-CMV IgG antibodies about 18
      months after the negative sample; seroconversion was found in 10/26 (38.5%).
      Taking all 536 samples of urine or saliva examined by virus culture and pp65
      antigen detection during the study into account, 159 (29.6%) were positive by
      virus culture and 59 (11%) gave a positive result with the pp65 assay. These data
      demonstrate the high prevalence of CMV shedding and the high risk of CMV
      infection in children with Down syndrome attending a day-care center for mentally
      handicapped patients. The virus culture was more sensitive than the pp65 CMV
      antigen assay for CMV detection in both urine and saliva samples.

PMID- 10968880
TI  - Relevant prevalence of Mycoplasma hominis and Ureaplasma urealyticum serogroups
      in HIV-1 infected men without urethritis symptoms.
AB  - M. hominis and U. urealyticum are the better-known mycoplasma species pathogenic
      to the human genitourinary tract, causing mainly urethritis, bacterial vaginosis
      and pregnancy complications. In HIV-infected patients, the prevalence and role of
      these species is still not well known. The aim of this work was to determinate
      the prevalence of these species in this group of male patients (HIV group), in
      comparison to a group of men with clinical symptoms of urethritis (STD group). M.
      hominis was isolated from 7.5% patients (8/106) and U. urealyticum from 18.9%
      patients (20/106) from the HIV group, being among these 62.5% and 85% in
      significant concentrations, respectively. In the STD group these rates were 0.9%
      (1/110) for M. hominis and 13.6% (15/110) for U. urealyticum, being 100% and
      93.3% in significant concentrations, respectively. We could demonstrate infection
      rates by these mycoplasma species in the HIV group as high as the one found in
      the STD one, what may indicate the occurrence of opportunistic infections in our
      population. This fact is discussed here because in immunosuppressed patients,
      specially M. hominis has been reported causing severe infections, even
      systemically.

PMID- 10968881
TI  - Predictive factors for response to lamivudine in chronic hepatitis B.
AB  - BACKGROUND: Lamivudine has been shown to be an efficient drug for chronic
      hepatitis B (CHB) treatment. AIM: To investigate predictive factors of response,
      using a quantitative method with high sensitivity. METHODS: We carried out a
      prospective trial of lamivudine in 35 patients with CHB and evidence for viral
      replication, regardless to their HBeAg status. Lamivudine was given for 12 months
      at 300 mg daily and 150 mg thereafter. Response was considered when DNA was
      undetectable by PCR after 6 months of treatment. Viral replication was monitored
      by end-point dilution PCR. Mutation associated with resistance to lamivudine was
      detected by DNA sequencing in non-responder patients. RESULTS: Response was
      observed in 23/35 patients (65.7%) but only in 5/15 (33.3%) HBeAg positive
      patients. Only three pre-treatment variables were associated to low response:
      HBeAg (p = 0.006), high viral load (DNA-VHB > 3 x 10(6) copies/ml) (p = 0.004)
      and liver HBcAg (p = 0. 0028). YMDD mutations were detected in 7/11 non-responder
      patients. CONCLUSIONS: HBeAg positive patients with high viral load show a high
      risk for developing drug resistance. On the other hand, HBeAg negative patients
      show a good response to lamivudine even with high viremia.

PMID- 10968882
TI  - Detection of hepatitis A antibodies by ELISA using saliva as clinical samples.
AB  - The possibility of detecting acute infection and immunity using body fluids that
      are easier to collect than blood, mainly in children, would facilitate the
      investigation and follow-up of outbreaks of hepatitis A (HAV). Our study was
      carried out to evaluate the detection of anti-HAV IgM, IgA and total antibodies
      in saliva using serum samples as reference. Forty three paired serum and saliva
      samples were analyzed. From this total, 24 samples were obtained from children
      and 1 from one adult during the course of acute hepatitis A; an additional 18
      samples were obtained from health professionals from Adolfo Lutz Institute. The
      sensitivity to detect anti-HAV IgM was 100% (95%CI: 79.1 to 100.0%), employing
      saliva as clinical samples. In detecting anti-HAV IgA, the sensitivity was 80. 8%
      (95%CI: 60.0 to 92.7%) and for the total antibodies was 82.1% (95%CI: 62.4 to
      93.2%). The specificity was 100% for each. The rate of agreement was high
      comparing the results of serum and saliva samples for detecting HAV antibodies.
      We conclude that saliva is an acceptable alternative specimen for diagnosing
      acute hepatitis A infection, and for screening individuals to receive hepatitis A
      vaccine or immunoglobulin.

PMID- 10968883
TI  - Epidemiological analysis of bacterial strains involved in hospital infection in a
      university hospital from Brazil.
AB  - Hospital infections cause an increase in morbidity and mortality of hospitalized
      patients with significant rise in hospital costs. The aim of this work was an
      epidemiological analysis of hospital infection cases occurred in a public
      University Hospital in Rio de Janeiro. Hence, 238 strains were isolated from 14
      different clinical materials of 166 patients hospitalized in the period between
      August 1995 and July 1997. The average age of the patients was 33.4 years, 72.9%
      used antimicrobials before having a positive culture. The most common risk
      conditions were surgery (19.3%), positive HIV or AIDS (18.1%) and lung disease
      (16.9%). 24 different bacterial species were identified, S. aureus (21%) and P.
      aeruginosa (18.5%) were predominant. Among 50 S. aureus isolated strains 36% were
      classified as MRSA (Methicillin Resistant S. aureus). The Gram negative bacteria
      presented high resistance to aminoglycosides and cephalosporins. A diarrhea
      outbreak, detected in high-risk neonatology ward, was caused by Salmonella
      serovar Infantis strain, with high antimicrobial resistance and a plasmid of high
      molecular weight (98Mda) containing virulence genes and positive for R factor.

PMID- 10968884
TI  - Migration and urban schistosomiasis. The case of Sao Lourenco da Mata, northeast
      of Brazil.
AB  - A population-based case-control design was used to investigate the association
      between migration, urbanisation and schistosomiasis in the Metropolitan Region of
      Recife, Northeast of Brazil. 1022 cases and 994 controls, aged 10 to 25, were
      selected. The natives and the migrants who come from endemic areas have a similar
      risk of infection. On the other hand, the risk of infection of migrants from
      nonendemic areas seems to be related with the time elapsed since their arrival in
      Sao Lourenco da Mata; those who have been living in that urban area for 5 or more
      years have a risk of infection similar to that of the natives. Those arriving in
      the metropolitan region of Recife mostly emigrate from "zona da mata" and "zona
      do agreste" in the state of Pernambuco. Due to the changes in the sugar
      agroindustry and to the increase in the area used for cattle grazing these
      workers were driven to villages and cities. The pattern of urbanisation created
      the conditions for the establishment of foci of transmission in Sao Lourenco da
      Mata.

PMID- 10968885
TI  - Heart rate responses to a muscarinic agonist in rats with experimentally induced
      acute and subacute chagasic myocarditis.
AB  - We administered arecoline to rats, with experimentally induced chagasic
      myocarditis, in order to study the sinus node sensitivity to a muscarinic
      agonist. Sixteen month old rats were inoculated with 200,000 T. cruzi parasites
      ("Y" strain). Between days 18 and 21 (acute stage), 8 infected rats and 8 age
      matched controls received intravenous arecoline as a bolus injection at the
      following doses: 5. 0, 10.0, 20.0, 40.0, and 80.0 microg/kg. Heart rate was
      recorded before, during and after each dose of arecoline. The remaining 8
      infected animals and 8 controls were subjected to the same experimental procedure
      during the subacute stage, i.e., days 60 to 70 after inoculation. The baseline
      heart rate, of the animals studied during the acute stage (349 +/- 68 bpm, mean
      +/- SD), was higher than that of the controls (250 +/- 50 bpm, p < 0.005). The
      heart rate changes were expressed as percentage changes over baseline values. A
      dose-response curve was constructed for each group of animals. Log scales were
      used to plot the systematically doubled doses of arecoline and the induced-heart
      rate changes. The slope of the regression line for the acutely infected animals
      (r = - 0.99, b =1.78) was not different from that for the control animals (r = -
      0.97, b = 1.61). The infected animals studied during the subacute stage (r = -
      0.99, b = 1.81) were also not different from the age-matched controls (r = -
      0.99, b = 1.26, NS). Consequently, our results show no pharmacological evidence
      of postjunctional hypersensitivity to the muscarinic agonist arecoline.
      Therefore, these results indirectly suggest that the postganglionic
      parasympathetic innervation, of the sinus node of rats with autopsy proved
      chagasic myocarditis, is not irreversibly damaged by Trypanosoma cruzi.

PMID- 10968886
TI  - The use of cyclosporine modifies the clinical and histopathological presentation
      of tuberculosis after renal transplantation.
AB  - Tuberculosis is one of the most frequent opportunistic infections after renal
      transplantation and occurred in 30 of 1264 patients transplanted between 1976 and
      1996 at Hospital Sao Paulo - UNIFESP and Hospital Dom Silverio, Brazil. The
      incidence of 2.4% is five times higher than the Brazilian general population. The
      disease occurred between 50 days to 18 years after the transplant, and had an
      earlier and worse development in patients receiving azathioprine, prednisone and
      cyclosporine, with 35% presenting as a disseminated disease, while all patients
      receiving azathioprine and prednisone had exclusively pulmonary disease. Ninety
      percent of those patients had fever as the major initial clinical manifestation.
      Diagnosis was made by biopsy of the lesion (50%), positivity to M. tuberculosis
      in the sputum (30%) and spinal cerebral fluid analysis (7%). Duration of
      treatment ranged from 6 to 13 months and hepatotoxicity occurred in 3 patients.
      The patients who died had a significant greater number of rejection episodes and
      received higher doses of corticosteroid. In conclusion, the administration of
      cyclosporine changed the clinical and histopathological pattern of tuberculosis
      occurring after renal transplantation.

PMID- 10968887
TI  - Central nervous system paracoccidioidomycosis. Report of a case successfully
      treated with itraconazol.
AB  - Paracoccidioidomycosis (PCM) is a primary pulmonary infection that often
      disseminates to other organs and systems. Involvement of the central nervous
      system (CNS) is rare and due to the fact that both clinical alertness and
      establishment of the diagnosis are delayed, the disease progresses causing
      serious problems. We report here a case of neuroparacoccidioidomycosis (NPCM),
      observed in a 55 year-old male, who consulted due to neurological symptoms (left
      hemiparesis, paresthesias, right palpebral ptosis, headache, vomiting and tonic
      clonic seizures) of a month duration. Upon physical examination, an ulcerated
      granulomatous lesion was observed in the abdomen. To confirm the diagnosis a
      stereotactic biopsy was taken; additionally, mycological tests from the ulcerated
      lesion and a bronchoalveolar lavage were performed. In the latter specimens, P.
      brasiliensis yeast cells were visualized and later on, the brain biopsy revealed
      the presence of the fungus. Treatment with itraconazole (ITZ) was initiated but
      clinical improvement was unremarkable; due to the fact that the patient was
      taking sodium valproate for seizure control, drug interactions were suspected and
      confirmed by absence of ITZ plasma levels. The latter medication was changed to
      clonazepam and after several weeks, clinical improvement began to be noticed and
      was accompanied by diminishing P. brasiliensis antigen and antibody titers. In
      the PCM endemic areas, CNS involvement should be considered more often and the
      efficacy of itraconazole therapy should also be taken into consideration.

PMID- 10968888
TI  - Toxocara seroprevalence in children from a subtropical city in Argentina.
AB  - Most studies from Argentina have focused on toxocariasis as an environmental
      problem of big cities, and there are no available data about children infection
      from small or middle-sized cities. In order to assess the prevalence of anti
      Toxocara antibodies in infantile population, 206 children from Resistencia, of
      both sexes, aged 1-14 years old were studied by Elisa testing with E/S T. canis
      L2 antigens. Hematological parameters and immunoglobulin levels were determined;
      five days' stool samples were studied and epidemiological data were obtained by
      means of a questionnaire to parents. Results showed that 73% of the children had
      one or more dogs living at home, 57% reported geophagia and 37.9% were positive
      for Toxocara serology, but there was no significant difference in prevalence
      neither for boys and girls, nor concerning age. An increased risk of infection
      was observed in age groups 5-6 and 7-8 for boys, and in age groups 3-4 and 5-6
      for girls.

PMID- 10968889
TI  - 'Equivocal' antiphospholipid syndrome.

PMID- 10968890
TI  - Structure-function studies on beta 2-glycoprotein I.
AB  - Human beta 2-glycoprotein I is a heavily glycosylated plasma protein which has
      been implicated in the binding of antiphospholipid antibodies to negatively
      charged phospholipids; a process considered as an important risk factor for the
      development of thrombosis. We have solved the crystal structure of beta 2
      glycoprotein I. In this review we will discuss what the three-dimensional
      structure teaches us about the role of beta 2-glycoprotein I in the pathogenesis
      of the antiphospholipid syndrome.

PMID- 10968891
TI  - Epitope studies with anti-beta 2-glycoprotein I antibodies from autoantibody and
      immunized sources.
AB  - This paper examines the methodology of anti-beta(2)-glycoprotein I (beta(2)-GPI)
      epitope determination and provides further epitope studies using human sera
      containing anti-beta(2)-GPI autoantibodies. Studies in this field may be
      misleading as the antigen coating density using mutant forms of beta(2)-GPI may
      be below the threshold required for monogamous divalent binding by low affinity
      anti-beta(2)-GPI autoantibodies, while being easily detected by high affinity
      anti-beta(2)-GPI from immunized animals. The antigen density threshold effect is
      found in anti-beta(2)-GPI autoantibodies from humans and from monoclonal anti
      beta(2)-GPI derived from mice with models of autoimmune disease. Anti-beta(2)-GPI
      from an autoimmune mouse and from 18/21 human sera did not bind above background
      levels to a domain-I-deleted mutant. In addition, single point mutations in
      domain I result in dramatic changes in the binding of many human sera containing
      anti-beta(2)-GPI. These findings support a conclusion that domain I of beta(2)
      GPI contains significant epitopes for the anti-beta(2)-GPI antibodies found in
      the antiphospholipid syndrome.

PMID- 10968892
TI  - Beta 2-glycoprotein I-anti-beta 2-glycoprotein I interaction.

PMID- 10968893
TI  - Should we include anti-prothrombin antibodies in the screening for the
      antiphospholipid syndrome?
AB  - Anti-prothrombin antibodies belong to the family of the antiphospholipid
      antibodies. Their prevalence ranges from 50 to 90% of antiphospholipid-positive
      patients, depending on the laboratory methodology employed for their detection.
      ELISA techniques are the most commonly used methods for their measurements, which
      allow a quick determination of their titer and isotype(s). Unfortunately, no well
      standardized assays are yet commercially available. The clinical relevance of
      anti-prothrombin antibodies as risk factors for thromboembolic events has been
      investigated by a number of retrospective and case-control studies. We reviewed
      11 studies: data on 1,440 patients and 371 sex- and age-matched controls were
      available. Seven studies reported a significant association between anti
      prothrombin antibodies and thrombosis by univariate analysis. Multivariate
      analysis was performed in five studies: only two of them confirmed the
      association. The sensitivity and specificity of anti-prothrombin antibodies for
      thrombosis were analysed according to the antibody isotype and to the arterial
      and/or venous site of thrombosis. The sensitivities are disappointingly low,
      particularly when the M isotype and arterial thrombosis are considered, whereas
      the specificities are somewhat better, even though they range widely. These data
      do not allow to recommend the measurement of anti-prothrombin antibodies in the
      routine laboratory workout of antiphospholipid-positive patients in order to
      define their thrombotic risk.

PMID- 10968895
TI  - The anticoagulant and anti-inflammatory roles of the protein C anticoagulant
      pathway.
AB  - Recent research has revealed a number of links between inflammation and
      coagulation. The protein C anticoagulant pathway appears to be the major pathway
      involved in the cross-talk between inflammation and coagulation. Studies indicate
      that inflammatory mediators can downregulate key components of the pathway
      through transcriptional control, proteolytic inactivation and oxidant damage. In
      turn, in vivo and in vitro studies have revealed mechanisms by which the
      components of the pathway may inhibit inflammatory responses. These include
      inhibition of cytokine responses to endotoxin, inhibition of leukocyte attachment
      to the activated endothelium and inhibition of thrombin and factor Xa generation
      in the microcirculation where both enzymes can lead to endothelial cell
      activation, further potentiating the inflammatory response. The ability of the
      protein C system to modulate both inflammation and coagulation may explain i part
      why specific defects in the pathway appear to be associated with both arterial
      and venus thrombosis.

PMID- 10968894
TI  - Antiphospholipid antibody-mediated disruption of the annexin-V antithrombotic
      shield: a thrombogenic mechanism for the antiphospholipid syndrome.
AB  - The mechanism(s) for thrombosis and pregnancy losses in the anti-phospholipid
      antibody syndrome have not yet been established. Annexin-V is an anionic
      phospholipid-binding protein with potent anticoagulant activity. The protein has
      been shown to be necessary for the maintenance of placental integrity and may
      play a thromboregulatory role at the maternal-fetal interface. There, it
      assembles over the apical surfaces of the placental villi and shields the
      underlying anionic phospholipids from availability for complexation with
      coagulation proteins. We have proposed that thrombosis and pregnancy loss in the
      antiphospholipid syndrome may be due to the disruption of the annexin-V shield by
      antiphospholipid (and co-factor) antibodies. The data accumulated from tissue
      immunohistochemistry, trophoblast and endothelial cell culture studies,
      coagulation studies using non-cellular phospholipids, and competition studies on
      artificial phospholipid bilayer are consistent with this hypothesis.

PMID- 10968896
TI  - Antiphospholipid antibodies, malignancies and paraproteinemias.

PMID- 10968897
TI  - Recent advances in antiphospholipid antibody-related valvulopathies.

PMID- 10968898
TI  - Kidney involvement in the antiphospholipid syndrome.

PMID- 10968899
TI  - Differential diagnosis of central nervous system manifestations of the
      antiphospholipid antibody syndrome.
AB  - Anti-phospholipid antibodies (aPL) have been associated with a variety of
      neurologic manifestations. The evidence for an association between aPL and most
      of these is weak because (1) no association actually exists, (2) the
      manifestation is rare or (3) sufficiently powered studies have not been
      performed. The only neurologic manifestation that is considered to have
      sufficient evidence to justify it being a part of the criteria for the diagnosis
      of Anti-phospholipid Antibody Syndrome (APS) is cerebral ischemia. In this mini
      review, most of the neurologic syndromes with an actual or suspected association
      with aPL are considered. The role of aPL in the differential diagnosis of these
      syndromes is considered as well.

PMID- 10968900
TI  - The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and
      systemic lupus erythematosus.
AB  - Since its description in 1965, Sneddon syndrome (SNS) is usually characterized by
      the association of an ischemic cerebrovascular disease and a widespread livedo
      reticularis. The presence of many other manifestations suggests that it is a
      systemic syndrome. The prevalence of anti-phospholipid antibodies (aPL) is highly
      variable, 41% in our experience. Comparison of patients with or without aPL
      showed that the fishnet of the livedo was clearly larger in aPL-negative patients
      who nevertheless, did not develop thrombocytopenia. Seizures and clinically
      audible mitral regurgitation were more frequently observed in aPL-positive
      patients. These data lead to consider that SNS is not a unique entity. As
      patients with primary anti-phospholipid syndrome (APS) and SNS did not differ
      from those with livedo reticularis, ischemic cerebral events and APS within
      systemic lupus erythematosus (SLE), there is no reason today to exclude patients
      with SLE. On one hand, SNS might cover a continuum spectrum joining diverse
      clinico-biological entities ranging from aPL-negative to SLE-related cases, with
      primary APS-SNS standing amidst. On the other hand, one might speculate that SNS
      should be regarded as a nearly similar clinical expression of two distinct
      disorders, i.e. a peculiar form of APS characterized by preferential arteriolar
      involvement or on the opposite a primary non-aPL related small artery disease
      mainly involving brain and skin vessels.

PMID- 10968901
TI  - Epidemiology of the antiphospholipid antibody syndrome.
AB  - The prevalence of antiphospholipid antibodies in normals and SLE patients is
      reviewed. The frequency of complications of antiphospholipid antibodies
      (thrombosis, pregnancy morbidity) in the literature and in the Hopkins Lupus
      Cohort is summarized.

PMID- 10968902
TI  - Ethnicity and APS.
AB  - Ethnic and geographic studies have contributed to knowledge of the clinical
      epidemiology of APS. In general, these studies support the associations of aPL
      with thrombosis and pregnancy morbidity, with some exceptions. Further
      investigation is needed to determine whether the exceptions represent interethnic
      variation in the clinical associations of aPL and thus provide clues to the
      causation of APS, or alternatively, whether methodologic factors are responsible.

PMID- 10968903
TI  - Long-term prognosis of antiphospholipid syndrome in patients with systemic lupus
      erythematosus.

PMID- 10968904
TI  - Which are the best biological markers of the antiphospholipid syndrome?
AB  - The diagnosis of antiphospholipid syndrome (APS) requires the presence of both
      clinical and biological features. Due to the heterogeneity of anti-phospholipid
      antibodies (aPL) the laboratory approach for their detection includes clotting
      based tests for lupus anticoagulant (LA) as well as solid-phase assays for
      anticardiolipin antibodies (aCL). In addition, as it has been shown that
      autoimmune aPL recognize epitopes on phospholipid (PL)-binding plasma proteins,
      assays detecting antibodies to beta 2-glycoprotein I (beta 2-GPI) or prothrombin
      have been developed. The association between venous or arterial thrombosis and
      recurrent fetal loss with the presence of conventional aPL (LA and/or aCL) has
      been confirmed by many studies. The LA and IgG aCL at moderate/high titre seem to
      exhibit the strongest association with clinical manifestations of the APS.
      Several reports indicate that LA is less sensitive but more specific than aCL for
      the APS. Assays against PLs other than CL as well as the use of mixtures of PLs
      have been proposed to improve the detection of APS-related aPL. Concerning
      antibodies to PL-binding proteins (detected in the absence of PLs), there is
      evidence that anti-beta 2-GPI are closely associated with thrombosis and other
      clinical features of the APS. Moreover, these antibodies may be more specific in
      the recognition of the APS and in some cases may be present in the absence of aPL
      detected by standard tests. Many issues are still under debate and are discussed
      in this review, such as the problems of standardization of anti-beta 2-GPI
      assays, detection of the IgA isotype of aCL and anti-beta 2-GPI, the coagulation
      profiles of LA in the recognition of the thrombotic risk and the association of
      particular markers with subsets of patients with APS.

PMID- 10968905
TI  - Use of the dilute Russell viper venom time (dRVVT): its importance and pitfalls.
AB  - Antiphospholipid antibodies (APA) are now recognized as the most common cause of
      acquired thrombophilia. These antibodies may lead to thrombosis in both arterial
      and venous sites. Lupus anticoagulants (LA) are the most significant risk factor
      among the various APAs. The detection of LAs remains challenging to most
      laboratories. Multiple screening tests are recommended (e.g. APTT, dilute PT and
      dRVVT). The dRVVT is one of the most important screening procedures. In many
      instances, commercially available dRVVT systems include a screening reagent with
      low PL concentration and a confirmatory product with high PL concentration. There
      are a number of commercially available dRVVT test systems. These reagents vary in
      phospholipid origin and concentration as well as source of Russell viper venom
      (RVV). It is imperative for laboratories to be well informed regarding reagent
      composition and laboratory performance.

PMID- 10968906
TI  - Conceptions and misconceptions in testing for lupus anticoagulants.
AB  - The aim of the following presentation is to review certain technical issues
      complicating clotting tests for lupus anticoagulants (LA). This is a field
      riddled with incorrect and misleading studies which often make progress difficult
      and which are difficult to retract. Inconsistent test sensitivity comparisons are
      sometimes due to incorrect methods being used but are more often due to
      contamination with platelets and instrument effects. Time dependence of LA is
      often due to pH drift during incubation and probably all LA are immediate acting
      (at least in our hands). The use of platelets in confirmatory tests is dangerous
      and can lead to false-positive results in patients with anti-factor V and heparin
      like inhibitors.

PMID- 10968907
TI  - Anti-phosphatidylethanolamine (aPE) antibodies: a survey.
AB  - Reports of anti-phosphatidylethanolamine antibodies (aPE) with similar or
      identical pathogenic associations as those described for anticardiolipin (aCL)
      and anti-phosphatidylserine (aPS) are found in the literature. In some instances,
      aPE is the sole antiphospholipid antibody (aPL) observed. Lupus anticoagulant
      antibodies (LA) appear to represent a subset of aPE as hexagonal phase PE can
      specifically inhibit the LA ability to prolong clotting times. As documented for
      aPL to the negatively charged phospholipids (PL), plasma proteins have been
      implicated for a positive aPE signal in the ELISA. Other aPE appear independent
      of known PE-binding plasma proteins. Among the described PE-binding proteins are
      high and low molecular weight kininogens (HMWK and LMWK) and the HMWK-binding
      proteins, factor XI and prekallikrein. Recently prothrombin has been added to
      this list. The reports of aPE published since 1986 are reviewed and discussed in
      this presentation.

PMID- 10968908
TI  - Overview on anticardiolipin ELISA standardization.

PMID- 10968909
TI  - Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in
      murine atherosclerosis.
AB  - We have made consecutive studies to prove that autoimmune factors can influence
      the progression of atherosclerosis in inbred and transgenic mice. C57BL/6 as well
      as LDL-receptor deficient mice were immunized with heat shock protein 65. LDL-RD
      and apolipoprotein E knockout (apoE KO) mice were immunized with human B
      glycoprotein I. ApoE KO mice were immunized with oxidized LDL. In all immunized
      mice, a sustained humoral response to the provided antigen was elicited evident
      by high titers of antibodies by ELISA. A primary cellular immune response was
      also shown by thymidine incorporation studies employing the antigens in vitro.
      Immunization with hsp-65 and with beta 2-GPI served to enhance the progression
      atherosclerosis and led to an increase in the infiltration of CD3 in the
      subendothelial regions of the early plaques. Transfer of hsp-65 and beta 2-GPI
      reactive lymphocytes to syngenic mice led to enhancement of fatty streak
      formation. However, immunization with homologous oxLDL in apoE KO mice led to
      attenuation of lesion progression concomitant with the production of anti-oxLDL
      antibodies. Thus, autoimmune factors appear to influence early artherosclerosis
      progression in mice. If proven in humans these antigen specific responses may be
      harnessed for selective immunomodulation of the atherosclerotic plaque.

PMID- 10968910
TI  - Obstetric management of antiphospholipid syndrome.
AB  - The obstetric management of women with antiphospholipid (aPL) syndrome remains
      controversial. Despite recent advances, the controversies have been fueled by our
      limited understanding of the multi-factorial causes of aPL-associated pregnancy
      loss and the lack of data from randomized studies. We have escaped from the
      narrow confines of the concept of aPL pregnancy loss being purely thrombotic in
      aetiology and attention is now focused on the adverse effects of aPL on embryonic
      implantation and trophoblast invasion. Combined treatment with aspirin and
      heparin has been demonstrated in two randomized studies to lead to a high live
      birth rate in aPL pregnancies. However, successful pregnancies are characterized
      by a high rate of perinatal complications and some women are refractory to this
      treatment combination. In addition to addressing these issues, multi-centre
      studies, which should perhaps be internet based, are needed to identify those aPL
      that are causative of pregnancy complications and those that are not, the role of
      IVIG and the long-term follow-up of both mothers with aPL and their babies.

PMID- 10968911
TI  - Management of patients with antiphospholipid antibodies undergoing in vitro
      fertilization.
AB  - Infertility affects 10-15% of all married couples of reproductive age in the
      United States and results in substantial emotional distress and medical
      investment. Though it is uncertain whether antiphospholipid syndrome (APS) is a
      cause of infertility, inevitably there is a small proportion of women who have
      both APS and infertility. In turn, some of these patients are candidates for
      ovulation induction, with or without assisted reproductive technologies, such as
      in vitro fertilization and embryo transfer, in an attempt to achieve successful
      pregnancy. The medications used for ovulation induction cause an increase in
      ovarian estrogen production beyond that typical of a normal menstrual cycle.
      Clinicians are appropriately concerned about the potential adverse effects of
      this estrogen surge on the clinical status of women with autoimmune disease. For
      APS, a primary concern would be that of thrombosis or embolism.

PMID- 10968912
TI  - Hormonal contraception and replacement and the use of androgens in the
      antiphospholipid syndrome.

PMID- 10968913
TI  - Tissue factor pathway and the antiphospholipid syndrome.
AB  - Expression of tissue factor activity on cells in contact with flowing blood is
      the trigger for physiological coagulation as well as many types of thrombosis. A
      number of older observations and considerable recent data suggest that increased
      tissue factor activity is an important cause of hypercoagulability in the
      antiphospholipid syndrome. Potential mechanisms contributing to upregulation of
      the tissue factor pathway include increased expression of tissue factor due to
      increased transcription, increased functional activity of tissue factor molecules
      due to de-encryption and decreased activity of tissue factor pathway inhibitor.
      Autoantibodies and/or immune complexes appear to play a major role in enhanced
      tissue factor activity, although increased levels of inflammatory cytokines may
      also contribute. Anti-beta 2-glycoprotein I autoantibodies have been specifically
      implicated in the antibody-mediated enhancement of tissue factor activity.

PMID- 10968914
TI  - Antiphospholipid antibodies and the protein C pathway.
AB  - Among the mechanisms suggested for the prothrombotic activity of lupus
      anticoagulant and antiphospholipid antibodies is the direct inhibition of the
      anticoagulant activated protein C (APC) pathway. Although some pathological
      antibodies may be directed towards the proteins involved, we hypothesize that
      populations exist which selectively inhibit the APC complex as a result of
      differences in the phospholipid requirements of this complex as compared to those
      of the procoagulant complexes. The most prominent feature is the requirement for
      the presence of phosphatidylethanolamine in the membrane for APC anticoagulant
      function. This mimics the requirements for inhibitory activity of at least a
      subset of autoantibodies associated with thrombosis. The role of oxidation of the
      phospholipid in APC function and antibody reactivity is also discussed.

PMID- 10968915
TI  - New developments in viral peptides and APL induction.
AB  - The associations of antiphospholipid antibodies (aPL) with thrombosis and fetal
      death are well recognized, but the mechanism(s) that induce their production are
      not. We demonstrated induction of pathogenic aPL antibodies by immunization with
      foreign beta(2)-GPI, or synthetic peptides representing the PL-binding site of
      the beta(2)-GPI. These antibodies caused intrauterine fetal death and transverse
      myelopathy due to spinal cord infarction in mice, and activated endothelial cells
      in vitro. We also introduced aPL in mice by immunization with PL-binding viral
      peptides and observed their pathogenic effects. This study demonstrated that
      pathogenic effects of aPL antibodies induced by immunization with a human CMV
      derived PL-binding synthetic peptide. We hypothesize that in APS patients aPL is
      induced by beta(2)-GPL-like PL-binding products of human common bacteria or
      viruses.

PMID- 10968916
TI  - Apoptosis and the antiphospholipid syndrome.
AB  - The target of many antiphospholipid autoantibodies (APA) has been shown to be a
      complex between anionic phospholipid (PL) and the plasma protein beta 2
      glycoprotein I (beta 2-GPI), but the identity of the natural target(s) and/or
      immunogen for APA in vivo remains undetermined. The anionic PL of cell membranes
      represent important potential targets and immunogenes for APA. Although anionic
      PL are normally absent from the extracellular surface of cell membranes, they
      redistribute from the inner to the outer leaflet during apoptosis. We and others
      have shown that beta 2-GPI binds selectively to the surface of apoptotic, but not
      viable, cells, and that the binding of beta 2-GPI to the surface of apoptotic
      cells generates an epitope recognized by APA from patients with both primary
      antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). In this
      review, we discuss recent findings, which suggest not only that apoptotic cell
      bound beta 2-GPI is injected by non-intravenous routes. We also review briefly
      the potential role of oxidation in generating epitopes responsible for the
      recognition and induction of APA. Taken together, we believe that the available
      evidence supports a role for apoptotic cells as far as targets of APA and
      possible players in the induction of APA.

PMID- 10968917
TI  - Endothelial activation by aPL: a potential pathogenetic mechanism for the
      clinical manifestations of the syndrome.

PMID- 10968918
TI  - Experimental thrombosis and antiphospholipid antibodies: new insights.

PMID- 10968919
TI  - Primary prevention of thrombosis in subjects with positive antiphospholipid
      antibodies.
AB  - A major cause of stroke, as well as other arterial and venous thromboembolic
      disease has been identified-the presence of antiphospholipid antibodies (aPL).
      Now it is possible to identify individuals positive for aPL and still free of
      thrombosis. The tests to measure aPL have been standardized (aCL by ELISA and LA
      by coagulometric assays) and they are routinely performed in patients with SLE
      and other connective tissue diseases and women with recurrent pregnancy loss.
      However, very little is known about the risk of thrombosis in individuals
      positive for aPL but still free of thrombosis. Should these individuals receive
      any treatment? If so, which one?

PMID- 10968920
TI  - Do we know which patients with the antiphospholipid syndrome should receive long
      term high dose anti-coagulation?
AB  - The standard treatment of thrombosis related to antiphospholipid antibodies is
      lifelong high-intensity oral anticoagulation. This standard is primarily based on
      retrospective evaluations of such patients. In this paper we give a summary of
      current treatment of deep leg vein thrombosis, pulmonary embolism, ischaemic
      stroke and transient ischaemic events in the general population and relate this
      to studies performed in patients with the anti-phospholipid syndrome (APS). It is
      concluded that many patients with APS can be treated with conventional doses of
      oral anticoagulants, and that anti-platelet drugs may have a role in the
      prevention of cerebral ischaemic events. Data from large scale prospective
      studies, which are underway, will ultimately identify the optimal treatment in
      individual patients.

PMID- 10968921
TI  - Future trends for treatment of APS.
AB  - Since the Sapporo Anti-phospholipid Antibody Conference we have learned much
      about the molecular and genetic biology of antiphospholipid antibody, its
      mechanisms of pathogenesis, detailed clinical descriptions of illness, including
      tests of criteria, definitions of subsets of disease, and early intimations about
      long-term prognosis. There has been wide application of known treatments but
      little testing of new ones. Rapid advances in the basic science of this illness
      gives us an opportunity to devise, test, and generally apply targeted biologic
      agents in order to prevent the short-term and long-term complications of this
      disease.

PMID- 10968922
TI  - Antiphospholipid syndrome and heparin-induced thrombocytopenia: update on
      similarities and differences.

PMID- 10968923
TI  - Speculations on APS in the coming millennium.

PMID- 10968924
TI  - Serial control of phonology in speech production: a hierarchical model.
AB  - A dynamic oscillator-based model of the sequencing of phonemes in speech
      production (OSCAR) is described. An analysis of phoneme movement errors
      (anticipations, perseverations, and exchanges) from a large naturalistic speech
      error corpus provides a new set of data suitable for quantitative modeling and is
      used to derive a set of constraints that any speech-production model must
      address. The new computational model is shown to account for error type
      proportions, movement error distance gradients, the syllable-position effect, and
      phonological similarity effects. The model provides an alternative to frame-based
      accounts, serial buffer accounts, and associative chaining theories of serial
      order processing in speech.

PMID- 10968925
TI  - Diagnostic colors mediate scene recognition.
AB  - In this research, we aim to ground scene recognition on information other than
      the identity of component objects. Specifically we seek to understand the
      structure of color cues that allows the express recognition of scene gists. Using
      the L*a*b* color space we examined the conditions under which chromatic cues
      concur with brightness to allow a viewer to recognize scenes at a glance. Using
      different methods, Experiments 1 and 2 tested the hypothesis that colors do
      contribute when they are diagnostic (i.e., predictive) of a scene category.
      Experiment 3 examined the structure of colored cues at different spatial scales
      that are responsible for the effects of color diagnosticity reported in
      Experiments 1 and 2. Together, the results suggest that colored blobs at a coarse
      spatial scale concur with luminance cues to form the relevant spatial layout that
      mediates express scene recognition.

PMID- 10968926
TI  - The influence of life history and diet on the distribution of catarrhine primates
      during the Pleistocene in eastern Asia.
AB  - Environmental changes during the Pleistocene in eastern Asia had profound impacts
      on the distributions of mammalian groups. Critical for many mammals were the
      southward latitudinal shifts of the tropical and subtropical vegetational zones,
      and decreases in the areas of these zones. Examination of the responses of
      members of a single clade, the Catarrhini, indicates that the main catarrhine
      genera of eastern Asia responded individually to the environmental changes in the
      Pleistocene. These responses were influenced by the life history parameters and
      diets of the genera involved. Those animals (macaques, langurs) with shorter
      gestation times, shorter weaning periods, shorter interbirth intervals, higher
      intrinsic rates of increase of population, and abilities to survive on a wider
      variety of vegetation in seasonal habitats were less adversely affected than
      those (gibbons, orangutans and the giant extinct hominoid, Gigantopithecus) with
      more protracted reproductive schedules, lower intrinsic rates of population
      increase and preferences for the higher quality foods (especially ripe fruits) of
      less seasonal environments. Hominids, while displaying "hyper-ape" life history
      parameters, increasingly overcame the constraints of these parameters through
      extrasomatic means not available to other catarrhines. This ability made possible
      their colonization, by the Late Pleistocene, of highly seasonal habitats such as
      tundra, which were off-limits to non-culture-bearing catarrhines.

PMID- 10968927
TI  - Postcranial functional morphology of Morotopithecus bishopi, with implications
      for the evolution of modern ape locomotion.
AB  - The large-bodied hominoid from Moroto, Uganda has until recently been known only
      from proconsulid like craniodental remains and some vertebrae with modern ape
      like features. The discovery of two partial femora and the glenoid portion of a
      scapula demonstrates that the functional anatomy of Morotopithecus differed
      markedly from other early and middle Miocene hominoids. Previous studies have
      consistently associated the vertebral remains with a short, stiff back and with
      orthograde postures. Although the proximal femur more closely resembles the
      femora of monkeys than of apes and suggests a moderate degree of hip abduction,
      the distal femur resembles those of extant large bodied apes and suggests a
      varied loading regime and an arboreal repertoire that may have included
      substantial vertical climbing. The femoral shaft displays uniformly thick
      cortical bone, beyond the range of thickness seen in extant primates, and
      signifies higher axial loading than is typical of most extant primates. The
      glenoid fossa is broad and uniformly curved as in extant suspensory primates.
      Overall, Morotopithecus is reconstructed as an arboreal species that probably
      relied on forelimb-dominated, deliberate and vertical climbing, suspension and
      quadrupedalism. Morotopithecus thus marks the first appearance of certain aspects
      of the modern hominoid body plan by at least 20 Ma. If the suspensory and
      orthograde adaptations linking Morotopithecus to extant apes are synapomorphies,
      Morotopithecus may be the only well-documented African Miocene hominoid with a
      close relationship to living apes and humans.

PMID- 10968928
TI  - Degenerative joint disease in African great apes: an evolutionary perspective.
AB  - Degenerative joint disease is investigated in the spine and major peripheral
      joints (shoulder, elbow, hip and knee) in samples of chimpanzees (Pan troglodytes
      schweinfurthii; P. troglodytes troglodytes), lowland gorillas (Gorilla gorilla
      gorilla), and bonobos (P. paniscus). The P. troglodytes schweinfurthii sample
      comes from Gombe National Park, Tanzania, while the other samples are derived
      from museum materials originally collected in west/central Africa. Total data for
      African ape samples include 5807 surfaces for ascertainment of vertebral
      osteophytosis, 12,479 surfaces for determination of spinal osteoarthritis, and
      1211 joints for evaluation of peripheral joint osteoarthritis. All apes display
      significantly less spinal disease than in a comparable human sample, and these
      differences are most likely a consequence of human biomechanical adaptations for
      bipedal locomotion. Apes are also generally less involved in the major peripheral
      joints than are humans, but human groups are themselves highly variable in
      prevalence of peripheral osteoarthritis. These data agree with other findings of
      low prevalence of degenerative joint prevalence in free-ranging apes, but
      contrast markedly with evidence derived from colony-reared Old World monkeys.

PMID- 10968929
TI  - Vocal responsiveness in male wild chimpanzees: implications for the evolution of
      language.
AB  - Several captive chimpanzees and bonobos have learned to use symbols and to
      comprehend syntax. Thus, compared with other nonhumans, these animals appear to
      have unusual cognitive powers that can be recruited for communicative behavior.
      This raises the possibility that wild chimpanzee vocal communication is more
      complex than heretofore demonstrated. To examine this possibility, I investigated
      whether wild chimpanzee vocal exchanges exhibit uniquely human conversational
      attributes. The results indicate that wild chimpanzees vocalize at low rates,
      tend not to respond to calls that they hear, and, when they do respond, tend to
      give calls that are similar to the ones they have heard. Thus, chimpanzee vocal
      interactions resemble those of other primate species, and show no special
      similarity to human conversations. The results support the view that we need to
      explore cognitive and social continuities and discontinuities with nonhuman
      primates to understand the origin and evolution of language, but also emphasize
      the need for fine-grained analyses of wild chimpanzee vocal interactions.

PMID- 10968930
TI  - The petrosal of Omomys carteri and the evolution of the primate basicranium.
AB  - The first omomyine petrosals, those of Omomys carteri, are described. Omomys
      probably had a tympanic bulla and canals for the intratympanic carotid
      circulation derived from the petrosal bone. The stapedial and promontory canals
      were complete, large and subequal. The posterior carotid foramen entered the
      bulla posteromedially. The intratympanic portion of the facial nerve was fully
      enclosed in bone, the stapedius fossa is extrabullar and the parotic fissure is
      patent. The mastoid was pneumatized from the epitympanic recess and a
      supracochlear cavity may have been present. The Omomys petrosals exhibit a
      generic omomyiform morphology, exhibiting no features that can be interpreted as
      autapomorphies and only one feature shared with adapiforms. The monophyly of
      Omomyiformes is based on other cranial characters, dental and postcranial
      characters assessed elsewhere. The similarity of the Shanghuang petrosal to the
      petrosals of omomyiforms, as well as the ambiguous evidence of its association,
      suggest that an omomyiform affinity for that petrosal cannot be ruled out.

PMID- 10968931
TI  - The Amud 7 skeleton--still a burial. Response to Gargett.

PMID- 10968932
TI  - A response to Hovers, Kimbel and Rak's argument for the purposeful burial of Amud
      7.

PMID- 10968933
TI  - Thermodynamics and evolution.
AB  - The science of thermodynamics is concerned with understanding the properties of
      inanimate matter in so far as they are determined by changes in temperature. The
      Second Law asserts that in irreversible processes there is a uni-directional
      increase in thermodynamic entropy, a measure of the degree of uncertainty in the
      thermal energy state of a randomly chosen particle in the aggregate. The science
      of evolution is concerned with understanding the properties of populations of
      living matter in so far as they are regulated by changes in generation time.
      Directionality theory, a mathematical model of the evolutionary process,
      establishes that in populations subject to bounded growth constraints, there is a
      uni-directional increase in evolutionary entropy, a measure of the degree of
      uncertainty in the age of the immediate ancestor of a randomly chosen newborn.
      This article reviews the mathematical basis of directionality theory and analyses
      the relation between directionality theory and statistical thermodynamics. We
      exploit an analytic relation between temperature, and generation time, to show
      that the directionality principle for evolutionary entropy is a non-equilibrium
      extension of the principle of a uni-directional increase of thermodynamic
      entropy. The analytic relation between these directionality principles is
      consistent with the hypothesis of the equivalence of fundamental laws as one
      moves up the hierarchy, from a molecular ensemble where the thermodynamic laws
      apply, to a population of replicating entities (molecules, cells, higher
      organisms), where evolutionary principles prevail.

PMID- 10968934
TI  - Fundamental theorem of natural selection and frequency-dependent selection:
      analysis of the matrix game diploid model.
AB  - Following Ewens' interpretation about Fisher's fundamental theorem of natural
      selection, the matrix game model for diploid populations undergoing non
      overlapping, discrete generations is investigated. The total genetic variance is
      decomposed and it is shown that the partial change in the mean fitness, which is
      equal to the additive genetic variance over the mean fitness, can be thought of
      as a change due only to the partial changes in the phenotypic frequencies.

PMID- 10968935
TI  - Neural network methods for identification and optimization of quantum mechanical
      features needed for bioactivity.
AB  - This paper presents a new approach to the discovery and design of bioactive
      compounds. The focus of this application will be on the analysis of enzymatic
      inhibitors. At present the discovery of enzymatic inhibitors for therapeutic use
      is often accomplished through random searches. The first phase of discovery is a
      random search through a large pre-fabricated chemical library. Many molecules are
      tested with refined enzyme for signs of inhibition. Once a group of lead
      compounds have been discovered the chemical intuition of biochemists is used to
      find structurally related compounds that are more effective. This step requires
      new molecules to be conceived and synthesized, and it is the most time-consuming
      and expensive step. The development of computational and theoretical methods for
      prediction of the molecular structure that would bind most tightly prior to
      synthesis and testing, would facilitate the design of novel inhibitors. In the
      past, our work has focused on solving the problem of predicting the bioactivity
      of a molecule prior to synthesis. We used a neural network trained with the
      bioactivity of known compounds to predict the bioactivity of unknown compounds.
      In our current work, we use a separate neural network in conjunction with a
      trained neural network in an attempt to gain insight as to how to modify existing
      compounds and increase their bioactivity.

PMID- 10968936
TI  - Possible role of endogenous retinoid (Vitamin A) toxicity in the pathophysiology
      of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of unknown
      etiology commonly affecting women. It is characterized by progressive destruction
      of the small intrahepatic bile ducts and portal inflammation, leading to fibrosis
      and cirrhosis. The major signs and symptoms of PBC, which include pruritus,
      lethargy, the sicca syndrome, and osteoporosis, closely resemble the
      manifestations of hypervitaminosis A. Based on a review of the literature and
      other observations connecting PBC with retinoid metabolism (vitamin A and its
      derivatives), the hypothesis is proposed that exposure to excess endogenous
      retinoids contributes to the pathogenesis of PBC and may be to the cause of some
      of the signs and symptoms associated with the disease.

PMID- 10968937
TI  - Information processing in multigame environments modeling the evolution of sex
      via punctuated equilibria.
AB  - Uncertain environments are properly described by probability distributions which,
      as usual, can be collapsed or conditioned into distributions with reduced
      uncertainty through the processing of environmental information. Organisms which
      force this collapse gain evolutionary advantage by being able to employ
      strategies in a known environment rather than in a merely probable one. The
      accrued benefit gained from processing information can be precisely quantified by
      comparing benefits returned using distributions prior to, and after collapse, and
      these often large and immediate benefits can amply justify the evolutionary cost
      of information processing systems. More importantly, the evolution of information
      processing systems must necessarily occur in a predictable evolutionary sequence
      from less complex to more complex. Practical applications include modeling the
      evolution of sex modeled here as a sequence from asexual reproduction, to single
      gene exchange, to gene packet exchange, to same species packet exchange, and
      finally to sexual reproduction, sexual selection, Red Queen contests and so on.
      Modeling this sequence requires extensions to game theory originally designed to
      model a single game, to allow the simultaneous operation of many games. This
      extension is called a multigame environment. The dynamical evolution of the
      development sequence shows punctuated equilibria.

PMID- 10968938
TI  - A simple model for the interplay of predators, rodents and food.
AB  - This paper presents a simple mathematical model for multiannual population
      cycles, in particular the periods, for the triple of small rodents and their
      predators and food. The parameters used are average birth rates of rodents and
      predators. The period lengths fit observations of lemmings and voles rather well
      and the model explains why the observed periods cluster around 4 years and around
      10 years.

PMID- 10968939
TI  - The survival of slow reproducers.
AB  - Multicellularity, and the attendant segregation of the germ line, entails the
      loss of reproductive capacity by the soma: in Volvox carteri, less than 1 cell in
      100 contributes to the next generation. However, compensatory advantages are
      unlikely to be very large (Koufopanou & Bell, 1993. Proc. R. Soc. Lond. (B)
      254,107-113). Somewhat similarly, sex implies the generation of males, hence a
      dramatic reproductive slowdown (Barton & Charlesworth, 1998. Science281, 1986
      1990); yet, a compensating (two-fold) advantage of sex has not been found. Here,
      I try to evaluate the actual cost of maintaining slow reproductive cycles, namely
      cycles that necessitate the production of "dead end" units such as somatic cells
      or males. In a quantitative model for the competition of individuals with
      different, heritable reproductive rates, this cost turns out to be unexpectedly
      small, and may even sometimes become irrelevant. The bases for this are made
      fairly clear: thus, when all enjoy high fecundity (e.g. a long reproductive life)
      the handicap of a slower reproduction vanishes; alternatively, a slight
      separation of ecological niches may be sufficient for survival of slower but
      otherwise unchanged reproducers; and finally, inherent to slow reproduction is a
      low rate of destabilizing genetic change. These facts are largely independent of
      the formal model details, and are supported by direct computer simulations. They
      give a quantitative basis for analysing the evolution and prevalence of slow life
      cycles. The implications of these findings for the evolution of multicellularity
      are briefly discussed.

PMID- 10968940
TI  - Transpiration and assimilation of early Devonian land plants with axially
      symmetric telomes-simulations on the tissue level.
AB  - Early terrestrial ancestors of the land flora are characterized by a simple,
      axially symmetric habit and evolved in an atmosphere with much higher
      CO(2)concentrations than today. In order to gain information about the
      ecophysiological interrelationships of these plants, a model dealing with their
      gaseous exchange, which is basic to transpiration and photosynthesis, is
      introduced. The model is based on gas diffusion inside a porous medium and on a
      well-established photosynthesis model and allows for the simulation of the local
      gas fluxes through the various tissue layers of a plant axis. Necessary
      parameters consist of kinetical properties of the assimilation process and other
      physiological parameters (which have to be taken from extant plants), as well as
      physical constants and anatomical parameters which can be obtained from well
      preserved fossil specimens. The model system is applied to an Early Devonian land
      plant, Aglaophyton major. The results demonstrate that, under an Early Devonian
      CO(2)concentration, A. major shows an extremely low transpiration rate and a low,
      but probably sufficiently high assimilation rate. Variation of the atmospheric
      CO(2)concentration shows that the assimilation is fully saturated even if the
      CO(2)content is decreased to about one-third of the initial value. This result
      indicates that A. major was probably able to exist under a wide range of
      atmospheric CO(2)concentrations. Further applications of this model system to
      ecophysiological studies of early land plant evolution are discussed.

PMID- 10968941
TI  - Daisyworld is Darwinian: constraints on adaptation are important for planetary
      self-regulation.
AB  - The Daisyworld model demonstrates that self-regulation of the global environment
      can emerge from competition amongst types of life altering their local
      environment in different ways. Robertson & Robinson (1998. J. theor. Biol.195,
      129-134) presented what they describe as a "Darwinian Daisyworld" in which the
      ability of organisms to adapt their internal physiology in response to
      environmental change undermines their ability to regulate their environment. They
      assume that there are no bounds on the environmental conditions that organisms
      can adapt to and that equal growth rates can potentially be achieved under any
      conditions. If adaptation could respond sufficiently rapidly to changes in the
      environment, this would eliminate any need for the environment to be regulated in
      the first place, because all possible states of the environment would be equally
      tolerable to life. However, the thermodynamics, chemistry and structure of living
      organisms set bounds on the range of environmental conditions that can be adapted
      to. As these bounds are approached, environmental conditions limit growth rate,
      and adaptations necessary for survival can also cost energy. Here we take account
      of such constraints and find that environmental regulation is recovered in the
      Daisyworld model. Hence, we suggest that constraints are an important part of a
      self-regulating planetary system.

PMID- 10968942
TI  - Feasibility of a sustained steep Ca(2+)Gradient in the cytosol of electrically
      non-excitable cells.
AB  - In electrically non-excitable cells the predominant mode of calcium signaling is
      a biphasic rise in cytosolic calcium concentration. It results from Ca(2+)release
      from intracellular stores, followed by Ca(2+)influx across the plasma membrane.
      It has been hypothesized that prolonged calcium influx may result in a sustained
      local elevation of the cytosolic calcium concentration near the plasma membrane.
      The mathematical model presented here evaluates the cytosolic concentration of
      Ca(2+)as a function of time and distance from the plasma membrane. It consists of
      cytoplasmic calcium stores and a plasma membrane, both equipped with calcium
      channels and pumps, and an immobile cytoplasmic calcium buffer. The model has
      verified quantitatively the feasibility of a stable Ca(2+)gradient in the cytosol
      with high values of Ca(2+)concentration near the plasma membrane and evaluated
      its properties as a function of different cellular parameters. The formation of
      the gradient does not require special distribution of the intracellular contents,
      channels and pumps. However, it requires buffering of the cytosolic calcium by
      the intracellular stores and that the rate of calcium release from the stores
      near the plasma membrane be higher than in other parts of the cell. We suggest
      that this model can provide an adequate description of the elevated calcium
      plateau generally observed in electrically non-excitable cells.

PMID- 10968943
TI  - A finite-element model for the mechanical analysis of skeletal muscles.
AB  - In the present paper, a finite-element model for simulating muscle mechanics is
      described. Based on nonlinear continuum mechanics an algorithm is proposed that
      includes the contractile active and passive properties of skeletal muscle. Stress
      in the muscle is assumed to result from the superposition of a passive and an
      active part. The passive properties are described by a hyperelastic constitutive
      material law whereas the active part depends on the fibre length, shortening
      velocity and an activation function. The constraint of approximate
      incompressibility of the muscle element is satisfied as a property of the
      constitutive equations. Because of the nonlinear behaviour of the material and
      the highly dynamical performance an incremental procedure including iterative
      methods is used. The advantage of the model over previous formulations is the
      possibility to integrate the element into an engineering standard finite-element
      programme ANSYS using advanced numerical tools. The model allows simulations of
      muscle recruitment, calculations of stress and strain distributions and
      predictions of muscle shape. Other possible applications are studies of the
      muscle architecture, the effect of inertia and impacts. First, simple examples
      are presented.

PMID- 10968944
TI  - System-theoretical (Holistic) approach to the modelling of structural-functional
      relationships of biomolecules and their evolution: an example of triterpene
      glycosides from sea cucumbers (Echinodermata, holothurioidea).
AB  - Triterpene glycosides from sea cucumbers (Holothurioidea, Echinodermata) are used
      as a model for studying the biochemical evolution for correlation between the
      glycoside membranolytic activity and biological functions. Concepts of
      evolutionary morphology are applied at the molecular level. The concept of Van
      der-Klaauve's- Dullemeijer's system-theoretical (holistic) approach is used for
      the model of structural-functional relationships of the glycosides. Network
      diagrams of structural-functional relationships have been prepared for many
      glycosides. The diagrams correlate well with experimental data and show a very
      complex and flexible action of the natural selection on the structural fragments
      of the glycosides. The diagrams also show overlapping in the functional
      components that provide stability to the general structural plan of glycosides
      during evolution. The method may be applied to other biomolecules.

PMID- 10968945
TI  - Acid tolerance in Listeria monocytogenes influences invasiveness of enterocyte
      like cells and macrophage-like cells.
AB  - Clinical and food Listeria monocytogenes isolates, pre-exposed to mild acidic
      conditions, were able to readily develop acid tolerance, irrespective of their
      origin. We attempted to investigate the influence of acid tolerance mechanisms,
      either constitutive or induced, on the invasive behaviour of this facultative
      food-borne pathogen. Entry efficiency and intracellular growth of acid-tolerant
      strains were evaluated in in vitro cell models capable to mimic in vivo target
      cells, such as enterocytes and macrophages. An acid-adapted L. monocytogenes wild
      type strain and a constitutively acid-tolerant mutant were able to enter
      enterocyte-like (Caco-2) cells as well as to survive and proliferate
      intracellularly in lipopolysaccharide-treated macrophage-like (J774.A1) cells, at
      a significant increased extent by respect of the non acid-adapted wild-type
      strain. These findings add new information about the influence of the acid
      tolerance response on L. monocytogenes virulence, suggesting that in acid-adapted
      bacteria the early events of pathogenesis which allow the colonization and the
      spread of bacteria in the host may be highly promoted.

PMID- 10968946
TI  - Molecular characterization and allelic distribution of the phage-mediated
      hyaluronidase genes hylP and hylP2 among group A streptococci from western
      Norway.
AB  - Forty-two isolates of group A streptococcus from patients with invasive and non
      invasive diseases in western Norway, belonging to the emm sequence types emml,
      emm3, emm6, emm22, emm28, emm75 and emm78 were screened by PCR for the phage
      mediated hyaluronidase genes hylP and hylP2. The amplified genes were
      characterized by nucleotide sequencing and/or by PCR-RFLP, with the objective of
      looking for possible associations between alleles of these two genes and
      invasiveness. The hylP was amplified from all isolates and two main alleles were
      found hylP-emm3 in all emm3 isolates and hylP-emm6A in all emm6 isolates, the
      latter possibly generated by an intergenic recombination between hylP and hylP2.
      The isolates of the other sequence types had either of these two alleles, or
      both. Only 27 isolates gave amplicons of the appropriate size with the primers
      targeting hylP2. Sequencing of these amplicons showed two main types: one was
      similar to the published hylP2 and the other (hylP-emm6B) was probably a variant
      of hylP. PCR-RFLP revealed the presence of both hylP-emm6B and hylP2 in at least
      six of the emm6 isolates. The alleles of both hylP and hylP2 seemed to have emm
      sequence type preferences. No association between invasiveness and specific phage
      mediated hyaluronidase genes/alleles or the production of extracellular
      hyaluronidase was observed.

PMID- 10968947
TI  - Comparison of pathogenic properties between two types of arginine-specific
      cysteine proteinases (gingipains-R) from Porphyromonas gingivalis.
AB  - Two major arginine-specific cysteine proteinases (gingipains R) from
      Porphyromonas gingivalis have been compared with regard to their potential
      participation in the pathology of periodontal disease. Both the high and low
      molecular mass forms, HRgpA and RgpB, cleaved oligopeptide fluorogenic substrates
      at the P1-arginine residue with essentially identical specificity but different
      efficiencies, with HRgpA being about 1.5 to seven-fold less potent than RgpB. In
      contrast HRgpA, which occurs as a non-covalent complex of catalytic and
      hemagglutinin/adhesion domains, was about two-fold more active than RgpB in
      degrading fibrinogen and fibrin, while both enzymes activated prekallikrein with
      similar efficiency. These data indicate the likelihood that both activities could
      be involved in both the bleeding tendency and production of gingival crevicular
      fluid, which occur at infected periodontitis sites. Significantly, however, is
      the fact that HRgpA, but not RgpB, was able to bind phospholipids in the presence
      of calcium ions, the effect dramatically enhancing the activation of clotting
      factors by this proteinase. This suggests that HRgpA may play a more important
      role in the virulence of Porphyromonas gingivalis, relative to RgpB, almost
      certainly because of the presence of the hemagglutinin/adhesion domain which can
      bind phospholipid and apparently modulate enzyme activity.

PMID- 10968948
TI  - Interaction of Bartonella bacilliformis with human erythrocyte membrane proteins.
AB  - Intracellular invasion is an important aspect of Carrion's disease caused by
      Bartonella bacilliformis. Both the hematic and tissue phases of the disease
      involve the initial attachment of the organism to erythrocytes and endothelial
      cells, respectively. Using two different approaches, preliminary evidence is
      provided that B. bacilliformis interacts with multiple surface-exposed proteins
      on human erythrocytes. Utilizing Western blot analysis, it was demonstrated that
      the organism binds several biotinylated erythrocyte proteins with approximate
      molecular masses of 230, 210, 100, 83 and 44 kDa. There was enhanced Bartonella
      binding to the 44 kDa protein and binding to a 25 kDa protein following exposure
      of intact red cells to trypsin. Moreover, there was a complete abrogation of
      binding to these proteins following exposure of erythrocytes to sodium
      metaperiodate oxidation, indicating the significance of carbohydrate moieties in
      the interactions of Bartonella with the erythrocyte. In a second approach,
      similar binding proteins or putative receptors were identified when Bartonella
      was co-incubated with isolated membrane proteins from red cell ghosts. A
      comparison of the molecular weights of these putative receptors with known
      erythrocyte proteins and their immunoreactivity to specific antisera suggested
      that the 230 and 210 kDa proteins are the alpha and beta subunits of spectrin;
      the 100 and 83 kDa proteins are band 3 protein and glycophorin A, respectively;
      and the 44 and 25 kDa proteins are the respective dimeric and monomeric forms of
      glycophorin B. Consistent with this notion was the binding of Bartonella to
      purified preparations of alpha and beta spectrin and glycophorin A/B.

PMID- 10968949
TI  - Aerosol infection of mice with recombinant BCG secreting murine IFN-gamma
      partially reconstitutes local protective immunity.
AB  - To better understand the contribution of interferon-gamma (IFN-gamma) to the
      immune response during the first 60 days of mycobacterial infection in the lungs,
      IFN-gamma gene disrupted (IFN-gamma-/-) mice were infected via aerosol with
      recombinant Mycobacterium bovis Bacillus Calmette-Guerin (BCG) secreting murine
      IFN-gamma (BCG-IFN-gamma) and compared to mice infected with recombinant BCG
      containing the vector only (BCG-vector). When IFN-gamma-/- mice were infected
      with BCG-vector, increasing bacillary loads and large undifferentiated granulomas
      that did not express inducible nitric oxide synthase (iNOS) were observed in the
      lungs. In contrast, infection with BCG-IFN-gamma resulted in reduced bacillary
      load and better differentiated granulomas containing epithelioid macrophages
      expressing iNOS as well as reduced levels of interleukin 10 (IL-10) mRNA.
      However, local production of IFN-gamma by the recombinant BCG did not protect IFN
      gamma-/- mice from subsequent challenge with M. tuberculosis. Infection of IFN
      gamma-/- peritoneal macrophages in vitro with BCG-IFN-gamma led to induction of
      iNOS expression and lower IL-10 mRNA levels. Nevertheless, the growth of the
      intracellular BCG was unaffected. Since IFN-gamma induced-iNOS protein and
      reduced IL-10 production were insufficient to control mycobacterial growth in
      vitro, the results suggest that additional mediator(s) present in vivo are
      required for control of mycobacterial growth.

PMID- 10968950
TI  - Effect of CD40 ligand and other immunomodulators on Pneumocystis carinii
      infection in rat model.
AB  - The corticosteroid-treated animal is well established as an experimental model
      for the study of Pneumocystis carinii pneumonitis (PCP). Latent or acquired
      infection with P. carinii in the murine lung progresses to fatal pneumonitis when
      the host is profoundly immunocompromized. In this study the effects of five
      immunomodulators; recombinant CD40 ligand (CD40L), bryostatin 1, recombinant FLT3
      ligand (FLT3L), recombinant granulocyte colony-stimulating factor (G-CSF) and
      recombinant interleukin-15 (IL-15) were investigated against PCP in a
      dexamethasone immunosuppressed Sprague-Dawley rat model. The majority of rats
      (70%) treated with CD40L at the onset of dexamethasone immunosuppression were
      protected against PCP. When CD40L was given after 10 days of immunosuppression,
      only 40% of the rats resolved the infection. However, 95% of the control animals
      developed PCP. Immunosuppressed rats treated with bryostatin 1, an immune
      activator had a partial (50%) protection against P. carinii infection. In
      contrast, daily administration of FLT3L, IL-15 or G-CSF provided no protection
      against P. carinii infection.

PMID- 10968951
TI  - Residual virulence of Brucella abortus in the absence of the cytochrome
      bc(1)complex in a murine model in vitro and in vivo.
AB  - To maintain survival in macrophages, Brucella must overcome a hostile phagosomal
      environment defined as low pH, limited nutrition and low oxygen tension. The
      specific mechanisms utilized by Brucella to surmount such unfavorable
      environmental factors in phagosomes are not well understood. In general, to adapt
      to a change in environmental oxygen tension, bacteria use different terminal
      oxidases that have different oxygen affinity. To survive in phagosomes where low
      oxygen tension exists, Brucella, like other bacteria, may require high oxygen
      affinity terminal oxidases that can accept electrons through a cytochrome
      bc(1)complex dependent or independent pathway. Using a Brucella abortus
      cytochrome bc(1)complex deficient mutant, delta fbcF, the requirement for a high
      oxygen affinity terminal oxidase governed by the cytochrome bc(1)complex
      dependent pathway was tested. The number of cfu from RAW 264.7 macrophage cells
      and spleens of BALB/c mice infected with wild-type or the cytochrome bc(1)complex
      deficient mutant was similar during the course of infection. These results
      suggest that B. abortus contains no essential terminal oxidase utilized at low
      oxygen tension in phagosomes requiring the cytochrome bc(1)complex.
      Alternatively, other branched cytochrome bc(1)complex independent respiratory
      mechanisms that contain the high oxygen affinity terminal oxidases likely exist
      to facilitate Brucella survival in phagosomes. This is the first investigation
      regarding the Brucella respiratory system at the molecular level and the
      involvement of a respiratory system in Brucella pathogenesis.

PMID- 10968952
TI  - Numerical studies of intermolecular multiple quantum coherences: high-resolution
      NMR in inhomogeneous fields and contrast enhancement in MRI.
AB  - A fast, efficient numerical algorithm is used to study intermolecular zero
      quantum coherences (iZQCs) and double-quantum coherences (iDQCs) in two
      applications where the three-dimensional structure of the magnetization is
      important: high-resolution NMR in inhomogeneous fields and contrast enhancement
      in MRI. Simulations with up to 2 million coupled volume elements (256 x 256 x 32)
      show that iZQCs can significantly narrow linewidths in the indirectly detected
      dimension of systems with inhomogeneous fields and explore the effects of shape
      and orientation of the inhomogeneities. In addition, this study shows that MR
      images from iZQC and iDQC CRAZED pulse sequences contain fundamentally new
      contrast, and a modified CRAZED pulse sequence (modCRAZED) can isolate the
      contrast from chemically inequivalent spins.

PMID- 10968953
TI  - Diffusion measurements at long observation times in the presence of spatially
      variable internal magnetic field gradients
AB  - Diffusion measurements in heterogeneous media may contain a significant source of
      error, the influence of the coupling between the applied and internal magnetic
      field gradients on the attenuation of the NMR signal. The application of bipolar
      magnetic field gradients has been introduced to suppress this error. The basic
      assumption for the successful removal of the coupling is that the diffusing
      molecules are experiencing a constant internal gradient during the experiment. We
      will provide theoretical and experimental evidence that the application of
      bipolar magnetic field gradients may fail to suppress the effect from all the
      cross terms between internal and applied gradients effectively at long
      observation times. It will be shown experimentally that a successful suppression
      of the cross terms is strongly dependent on the observation time, and on the tau
      value in the bipolar pulsed field gradient stimulated echo experiment. Copyright
      2000 Academic Press.

PMID- 10968954
TI  - Phase angle measurement from peak areas (PAMPAS)
AB  - A new method is described for accurate Phase Angle Measurement from Peak AreaS
      (PAMPAS) with the goal of facilitating automated phase correction of NMR spectra.
      PAMPAS measures phases of isolated NMR peaks by using Fourier analysis of a
      series of peak areas measured with systematically incremented phase shifts. The
      calculated phases of individual peaks can be employed to extract the zero- and
      first-order phase corrections by means of linear regression. The method is
      accurate, independent of the lineshape, robust, fast, and easy to implement.
      Copyright 2000 Academic Press.

PMID- 10968955
TI  - Simulations of chemical exchange lineshapes in CP/MAS spectra using floquet
      theory and sparse matrix methods
AB  - This paper presents a general method for simulating the effect of chemical
      exchange on MAS NMR spectra of solid samples. The complication in MAS spectra is
      that the Hamiltonian itself is time-dependent, due to the spinning of the sample.
      The approach taken in this work is to use Floquet theory to convert the problem
      into a time-independent form, and then use established methods (used in liquid
      NMR simulations) to calculate the lineshape. Floquet theory has been admired for
      its elegance, but criticized for its computational inefficiencies. This is
      because it removes the time dependence of the system by expanding the problem in
      a Fourier-like series. This makes a relatively small, time-dependent calculation
      into a much larger time-independent one. Typically, we use twice as many Floquet
      blocks as there are spinning sidebands, so the increase in size is substantial.
      The problem that this creates stems from the fact that the usual Householder
      methods for diagonalizing a matrix scale as the cube of the size of the matrix.
      This would make a Floquet calculation prohibitively long. However, the Floquet
      matrix is inherently sparse, so sparse matrix methods can produce substantial
      computational savings. Also, fully diagonalizing a matrix is expensive, but
      converting the matrix to a tridiagonal form (using iterative Lanczos methods) is
      much cheaper. The use of the Lanczos methods makes the Floquet calculations
      feasible as a general method for systems of more than one spin. We show how to
      set up the full matrix describing chemical exchange in a spinning sample, but the
      details of how the Lanczos methods work are not included-they are described
      elsewhere. We then validate the theory by simulating the MAS spectra of dimethyl
      sulfone both with natural abundance (13)C and with methyl groups labeled with
      (13)C. The latter system has both dipolar and chemical shielding anisotropy terms
      contributing to the spectrum. Copyright 2000 Academic Press.

PMID- 10968956
TI  - The nutation spin echo and its use for localized NMR
AB  - A suitably matched combination of unidirectional gradient pulses of the radio
      frequency amplitude B(1) and of the main magnetic field B(0) produces an
      unconventional type of spin echo, the nutation echo. The echo signal becomes
      volume selective if the gradients to be matched are inhomogeneously distributed
      in space. An example is a combination of a constant B(0) gradient and the
      inhomogeneous B(1) gradient of a surface coil. We suggest a method for localized
      NMR on this basis. Nutation echoes can also be used to map the spatial
      distribution of B(1) gradients of an arbitrary radio frequency coil geometry with
      the aid of a small probe sample. Copyright 2000 Academic Press.

PMID- 10968957
TI  - In vitro monitoring of total choline levels in a bioartificial pancreas: (1)H NMR
      spectroscopic studies of the effects of oxygen level.
AB  - This investigation implements specifically designed solvent-suppressed adiabatic
      pulses whose properties make possible the long-term monitoring of (1)H NMR
      detectable metabolites from alginate/poly-l-lysine/alginate (APA)-encapsulated
      betaTC3 cells. Our encapsulated preparations were maintained in a perfusion
      bioreactor for periods exceeding 30 days. During this prolonged cultivation
      period, the cells were exposed to repetitive hypoxic episodes of 4 and 24 h. The
      ratio of the total choline signal (3.20 ppm) to the reference signal (observed at
      0.94 ppm assigned to isoleucine, leucine, and valine) decreased by 8-10% for the
      4-h and by 20-32% for the 24-h episodes and returned to its prehypoxic level upon
      reoxygenation. The decrease in the mean value of total choline to reference
      signal ratio for three 4-h and two 24-h episodes in two different cultures was
      highly significant (P<0.01). The rate of recovery by this ratio was slower than
      the rates of recovery by oxygen consumption, lactate production, or glucose
      consumption. A step-up in oxygen level led to a new, higher value for the total
      choline to reference ratio. From spectra of extracts at 400 MHz, it was
      determined that 63.6% of the total choline signal is due to intracellular
      phosphorylcholine. Therefore, it is inferred that the observed changes in total
      choline signal are linked to an oxygen level dependence of the intracellular
      phosphorylcholine. Several possible mechanisms in which oxygen may influence
      phosphorylcholine metabolism are suggested. In addition, the implications of
      these findings to the development of a noninvasive monitoring method for tissue
      engineered constructs composed of encapsulated cells are discussed.

PMID- 10968958
TI  - RF pulse concatenation for spatially selective inversion
AB  - It is shown that spatially selective inversion and saturation can be achieved by
      concatenation of RF pulses with lower flip angles. A concatenation rule which
      enables global doubling of the flip angle of any given excitation pulse applied
      to initial z magnetization is proposed. In this fashion, the selectivity of the
      single pulse is preserved, making the high selectivity achievable in the low flip
      angle regime available for inversion and large flip-angle saturation purposes.
      The profile quality achievable with exemplary concatenated pulses is investigated
      in comparison with adiabatic inversion. It is verified that by using concatenated
      inversion in the transfer insensitive labeling technique (TILT), the MT artifact
      is suppressed. Copyright 2000 Academic Press.

PMID- 10968959
TI  - A Bayesian statistical method for the detection and quantification of rotational
      diffusion anisotropy from NMR relaxation data.
AB  - It has recently become more widely appreciated that the presence of rotational
      diffusional anisotropy in proteins and other macromolecules can have a
      significant affect on the interpretation of NMR relaxation data in terms of
      molecular motion. In this paper, we show how commonly used NMR relaxation data
      (R(1), R(2), and NOE) obtained at two spectrometer frequencies can be analyzed
      using a Bayesian statistical approach to reliably detect and quantify the degree
      of rotational diffusion anisotropy. Our approach differs from previous methods in
      that it does not make assumptions concerning the internal motions experienced by
      the residues which are used to quantify the diffusion anisotropy, but rather
      averages the results over all internal motions consistent with the data. We
      demonstrate our method using synthetic data corresponding to isotropic, axially
      symmetric anisotropic, and fully asymmetric anisotropic rotational diffusion, as
      well as experimental NMR data. We compare the Bayesian statistical approach with
      a widely used method for extracting tumbling parameters using both synthetic and
      experimental data. While it can be difficult to separate the effects of chemical
      exchange from rotational anisotropy using this "standard" method, these effects
      are readily separated using Bayesian statistics. In addition, we find that the
      Bayesian statistical approach requires considerably less CPU time than an
      equivalent standard analysis.

PMID- 10968960
TI  - Orientation-dependent (19)F dipolar couplings within a trifluoromethyl group are
      revealed by static multipulse NMR in the solid state.
AB  - The homonuclear dipolar coupling between the three equivalent (19)F-spins of a
      trifluoromethyl group, rotating about its threefold symmetry axis, was studied by
      multipulse solid-state NMR. A modified CPMG sequence was used first to resolve
      the dipolar splitting of a powder sample, and then to follow its orientation
      dependence in uniaxially aligned samples. Our aim is to employ the CF(3)-group as
      a highly sensitive reporter to describe the mobility and spacial alignment of
      (19)F-labeled molecules in biomembranes. As an example, the fluorinated anti
      inflammatory drug, flufenamic acid, was embedded as a guest compound in lipid
      bilayers. Undistorted (19)F dipolar spectra of its CF(3)-group were obtained
      without (1)H-decoupling, revealing a sharp triplet lineshape. When an oriented
      membrane sample was tilted in the magnetic field, the change in dipolar
      splittings confirmed that the guest molecule is motionally averaged about the
      membrane normal, as expected. A different behavior of flufenamic acid, however,
      was observed under conditions of low bilayer hydration. From this set of
      orientation-dependent lineshapes we conclude that the axis of motional averaging
      becomes aligned perpendicular to the sample normal. It thus appears that
      flufenamic acid induces a hexagonal phase in the membrane at low hydration.
      Finally, the dipolar (19)F NMR experiments were extended to frozen samples, where
      no molecular diffusion occurs besides the fast rotation about the CF(3)-axis.
      Also under these conditions, the CPMG experiment with composite pulses could
      successfully resolve the dipolar coupling between the three (19)F-nuclei.

PMID- 10968961
TI  - A time-domain algorithm for NMR spectral normalization.
AB  - Recently, a new method for quantitatively comparing NMR spectra of control and
      treated samples, in order to examine the possible occurring variations in cell
      metabolism and/or structure in response to numerous physical, chemical, and
      biological agents, was proposed. This method is based upon the utilization of the
      maximum superposition normalization algorithm (MaSNAl) operative in the frequency
      domain and based upon maximizing, by an opportune sign variable measure, the
      spectral region in which control and treated spectra are superimposed. Although
      the frequency-domain MaSNAl algorithm was very precise in normalizing spectra, it
      showed some limitations in relation to the signal-to-noise ratio and to the
      degree of diversity of the two spectra being analyzed. In particular, it can
      rarely be applied to spectra with a small number of visible signals not buried in
      the noise such as generally in vivo spectra. In this paper, a time-domain
      normalization algorithm is presented. Specifically, it consists in minimizing the
      rank of a Hankel matrix constructed with the difference of the two free induction
      decay signals. The algorithm, denoted MiRaNAl (minimum rank normalization
      algorithm), was tested by Monte Carlo simulations as well as experimentally by
      comparing two samples of known contents both with the new algorithms and with an
      older method using a standard. Finally, the algorithm was applied to real spectra
      of cell samples showing how it can be used to obtain qualitative and quantitative
      biological information.

PMID- 10968962
TI  - Correcting for incomplete saturation and off-resonance effects in multiple-site
      saturation-transfer kinetic measurements.
AB  - The effects of incomplete saturation and off-resonance irradiation on nuclear
      magnetic resonance saturation-transfer measurements of three-site chemical
      exchange rates are discussed. A new method that uses double-saturation
      measurements is compared with two published methods, one that uses single
      saturation measurements and one that uses a single-saturation measurement and a
      double-saturation measurement. Several formulas are compared for measuring the
      exchange rate constant k(DE) for exchange from a detected spin D to an exchanging
      spin E in the presence of exchange from spin D to a competing spin C. For each
      method, formulas are derived with corrections for incomplete saturation or off
      resonance effects, with both corrections, and with neither correction. Exact
      formulas are available for three exchanging sites with incomplete saturation if
      there are no off-resonance effects. Off-resonance corrections are imperfect even
      with complete saturation.

PMID- 10968963
TI  - Multiphoton resonances in pulse EPR
AB  - Two- and three-photon electron spin echoes of a two-level system are observed
      using, in addition to the microwave excitation, a linearly polarized radio
      frequency field oriented along the static magnetic field B(0). Such multiphoton
      echoes are detected when the sum of the energies of one microwave and one or two
      radio-frequency photons are equal to the difference between energies of two spin
      states. The multiphoton character of the echoes is confirmed by measuring the
      spin nutation frequency as a function of the angle between the radio-frequency
      field and B(0), and monitoring the echo amplitude as a function of the radiation
      field strengths. Floquet theory, usually applied for the description of
      multiphoton resonances with an odd number of photons, is extended to the case
      where an even number of photons participate in the transition. Copyright 2000
      Academic Press.

PMID- 10968964
TI  - Improved baseline recognition and modeling of FT NMR spectra
AB  - A new approach to baseline correction is presented. A smoothed spectrum is used
      for both baseline area recognition and modeling. To complete the model an
      interpolation technique is employed over the signals area; then the model is
      subtracted from the spectrum giving a flat baseline. The method has been shown to
      give excellent results even for spectra with large baseline distortions due to
      different origins. Copyright 2000 Academic Press.

PMID- 10968965
TI  - Efficient measurement of (3)J(N,Cgamma) and (3)J(C',Cgamma) coupling constants of
      aromatic residues in (13)C, (15)N-labeled proteins.
AB  - An NMR pulse sequence is proposed for the simultaneous determination of side
      chain chi1 torsion-angle related (3)J(N,Cgamma) and (3)J(C', Cgamma) couplings in
      aromatic amino acid spin systems. The method is of the quantitative J correlation
      type and takes advantage of attenuated (15)N and (1)H transverse relaxation by
      means of the TROSY principle. Unlike previously developed schemes for the
      measurement of either of the two coupling types, spectra contain internal
      reference peaks that are usually recorded in separate experiments. Therefore, the
      desired information is extracted from a single rather than four data sets. The
      new method is demonstrated with uniformly (13)C/(15)N labeled Desulfovibrio
      vulgaris flavodoxin, which contains 14 aromatic out of 147 total amino acid
      residues.

PMID- 10968966
TI  - Recoupling of heteronuclear dipolar interactions with rotational-echo double
      resonance at high magic-angle spinning frequencies.
AB  - Heteronuclear dipolar recoupling with rotational-echo double-resonance (REDOR) is
      investigated in the rapid magic-angle spinning regime, where radiofrequency
      irradiation occupies a significant fraction of the rotor period (10-60%). We
      demonstrate, in two model (13)C-(15)N spin systems, [1-(13)C, (15)N] and [2
      (13)C, (15)N]glycine, that REDOR DeltaS/S(0) curves acquired at high MAS rates
      and relatively low recoupling fields are nearly identical to the DeltaS/S(0)
      curve expected for REDOR with ideal delta-function pulses. The only noticeable
      effect of the finite pi pulse length on the recoupling is a minor scaling of the
      dipolar oscillation frequency. Experimental results are explained using both
      numerical calculations and average Hamiltonian theory, which is used to derive
      analytical expressions for evolution under REDOR recoupling sequences with
      different pi pulse phasing schemes. For xy-4 and extensions thereof, finite
      pulses scale only the dipolar oscillation frequency by a well-defined factor. For
      other phasing schemes (e.g., xx-4 and xx-4) both the frequency and amplitude of
      the oscillation are expected to change.

PMID- 10968967
TI  - Sideband patterns from rotor-encoded longitudinal magnetization in MAS recoupling
      experiments.
AB  - Recent multiple-quantum MAS NMR experiments have shown that a change in the rotor
      phase (and, hence, in the Hamiltonian) between the excitation and reconversion
      periods can lead to informative spinning-sideband patterns. However, such "rotor
      encoding" is not limited to multiple-quantum experiments. Here it is shown that
      longitudinal magnetization can also be rotor-encoded. Both homonuclear and
      heteronuclear rotor encoding of longitudinal magnetization (RELM) experiments are
      performed on dipolar-coupled spin-1/2 systems, and the corresponding sideband
      patterns in the indirect dimension are analyzed. In both cases, only even-order
      sidebands are produced, and their intensity distribution depends on the durations
      of the recoupling periods. In heteronuclear experiments using REDOR-type
      recoupling, purely dipolar sideband patterns that are entirely free of effects
      due to the chemical-shielding anisotropy can be generated. Advantages and
      disadvantages of the heteronuclear RELM experiment are discussed in the context
      of other methods used to measure heteronuclear dipolar couplings.

PMID- 10968968
TI  - Torus factor-The relationship between radiofrequency field and radial position in
      toroid cavity probes
AB  - Toroid detectors are resonators for high-pressure in situ NMR spectroscopy or one
      dimensional rotating-frame imaging. One of their unique qualities is a
      mathematically well-defined nonuniform radiofrequency field confined to the
      inside of the detector. A single parameter (i.e., the torus factor) is sufficient
      to describe the relationship between this radiofrequency field and the radial
      distance from the center axis of the torus. Because accurate determination of the
      torus factor is essential to optimize toroid cavity NMR experiments or conduct
      toroid cavity imaging, a fast numerical algorithm for accurate, precise, and
      convenient determination of torus factors from pulse width-dependent signal
      intensities is introduced. In addition, the new algorithm provides for 99%
      confidence intervals around the refined torus factors. A computer program in
      which the optimization progress is visualized during the torus factor refinement
      is presented. Upon completion of the program, the best-fit simulated data and the
      residuals between best fit and experimental data are provided. Copyright 2000
      Academic Press.

PMID- 10968969
TI  - An accurate and simple method for setting the magic angle for solid state NMR
      studies
AB  - Use of the deuterium NMR spectrum of a deuteriated solute dissolved in the
      nematic phase of a liquid crystal is suggested for setting the magic angle in
      solid state NMR. The use of the method as a convenient and accurate means of
      setting the angle is demonstrated. Copyright 2000 Academic Press.

PMID- 10968970
TI  - Two-dimensional PFG NMR for encoding correlations of position, velocity, and
      acceleration in fluid transport
AB  - A generalized approach to obtain two-dimensional maps of spatial particle
      coordinates and their derivatives with respect to time by PFG-NMR employing
      multiple gradient pulses is presented. A sequence of n magnetic field gradient
      pulses makes it possible, after independent stepping of each pulse and subsequent
      Fourier transformation, to plot the spin density distribution in coordinate space
      at n times and along the respective directions of the gradient pulses. In
      particular, two gradient pulses of effective area k(1) and k(2) separated by a
      time interval Delta lead to a plot of the combined two-time probability density,
      W(2)(r(1), 0; r(2), Delta), to find a particle at a coordinate r(1) at t = 0 and
      at r(2) at t = Delta. A conventional experiment for measuring transport
      properties by simultaneous stepping of the gradients under the condition k(1) = 
      k(2) is equivalent to a projection onto the secondary diagonal in the [r(1),
      r(2)] plot. The main diagonal represents an average position between the two
      timepoints t = 0 and t = Delta, so that a rotation of the coordinate plot by an
      angle of 45 degrees allows one to correlate the displacement R = r(2) - r(1) with
      the averaged position r parallel to the gradient direction. While an average
      velocity during the time interval Delta can be defined as &vmacr; = R/Delta, an
      extension toward acceleration and higher order derivatives is straightforward by
      modification of the pulse sequence. We discuss this concept by application to
      flow through a circular and a narrowing pipe (confusor), respectively, the
      experimental results of which are compared to numerical simulations. Copyright
      2000 Academic Press.

PMID- 10968971
TI  - REDOR with adiabatic dephasing pulses
AB  - The response of a spin (1/2) ensemble, at thermal equilibrium and experiencing
      chemical shift anisotropy (CSA), to the application of adiabatic inversion pulses
      has been studied under magic-angle spinning (MAS). Numerical simulations and
      experimental studies on such systems, carried out under slow spinning conditions,
      show that the response to adiabatic inversion pulses has much more favorable
      characteristics than the response to conventional rectangular pulses. We have
      also explored the possibilities of employing adiabatic 180 degrees pulses as
      dephasing pulses in rotational-echo double-resonance (REDOR) experiments. Our
      results show that it is indeed possible to employ such adiabatic inversion pulses
      conveniently in REDOR experiments to eliminate resonance offset and H(1)
      inhomogeneity effects which may arise from the usage of conventional rectangular
      180 degrees pulses. Copyright 2000 Academic Press.

PMID- 10968973
TI  - Two-dimensional pulsed TRIPLE at 95 GHz
AB  - The one-dimensional (1D) pulsed TRIPLE resonance experiment, introduced by
      Mehring et al. (M. Mehring, P. Hofer, and A. Grupp, Ber. Bunseges. Phys. Chem.
      91, 1132-1137 (1987)) is a modification of the standard Davies ENDOR experiment
      where an additional RF pi-pulse is applied during the mixing time. While the
      first RF pulse is set to one of the ENDOR transitions, the frequency of the
      second RF pulse is scanned to generate the TRIPLE spectrum. The difference
      between this spectrum and the ENDOR spectrum yields the difference TRIPLE
      spectrum, which exhibits only ENDOR lines that belong to the same M(S) manifold
      as the one selected by the first RF pulse. We have extended this experiment in
      two dimensions (2D) by sweeping the frequencies of both RF pulses. This
      experiment is particularly useful when the spectrum is congested and consists of
      signals originating from different paramagnetic centers. The connectivities
      between the peaks in the 2D spectrum enable a straightforward assignment of the
      signals to their respective centers and M(S) manifolds, thus providing the
      relative signs of hyperfine couplings. Carrying out the experiment at high fields
      has the additional advantage that nuclei with different nuclear gyromagnetic
      ratios are well separated. This is particularly true for protons which appear at
      significantly higher frequencies than other nuclei. The feasibility and
      effectiveness of the experiment is demonstrated at W-band (94.9 GHz) on a crystal
      of Cu(2+)-doped l-histidine. Homonuclear (1)H-(1)H, (14)N/(35)Cl-(14)N/(35)Cl and
      heteronuclear (1)H-(14)N/(35)Cl 2D TRIPLE spectra were measured and from the
      various connectivities in the 2D map the (1)H, (14)N, and (35)Cl signals that
      belong to two different Cu(2+) centers were identified and grouped according to
      their M(S) manifolds. Copyright 2000 Academic Press.

PMID- 10968972
TI  - Peptide internal motions on nanosecond time scale derived from direct fitting of
      (13)C and (15)N NMR spectral density functions.
AB  - NMR relaxation-derived spectral densities provide information on molecular and
      internal motions occurring on the picosecond to nanosecond time scales. Using
      (13)C and (15)N NMR relaxation parameters [T(1), T(2), and NOE] acquired at four
      Larmor frequencies (for (13)C: 62.5, 125, 150, and 200 MHz), spectral densities
      J(0), J(omega(C)), J(omega(H)), J(omega(H) + omega(C)), J(omega(H) - omega(C)),
      J(omega(N)), J(omega(H) + omega(N)), and J(omega(H) - omega(N)) were derived as a
      function of frequency for (15)NH, (13)C(alpha)H, and (13)C(beta)H(3) groups of an
      alanine residue in an alpha-helix-forming peptide. This extensive relaxation data
      set has allowed derivation of highly defined (13)C and (15)N spectral density
      maps. Using Monte Carlo minimization, these maps were fit to a spectral density
      function of three Lorentzian terms having six motional parameters: tau(0),
      tau(1), tau(2), c(0), c(1), and c(2), where tau(0), tau(1) and tau(2) are
      correlation times for overall tumbling and for slower and faster internal
      motions, and c(0), c(1), and c(2) are their weighting coefficients. Analysis of
      the high-frequency portion of these maps was particularly informative, especially
      when deriving motional parameters of the side-chain methyl group for which the
      order parameter is very small and overall tumbling motions do not dominate the
      spectral density function. Overall correlation times, tau(0), are found to be in
      nanosecond range, consistent with values determined using the Lipari-Szabo model
      free approach. Internal motional correlation times range from picoseconds for
      methyl group rotation to nanoseconds for backbone N-H, C(alpha)-H, and C(alpha)
      C(beta) bond motions. General application of this approach will allow greater
      insight into the internal motions in peptides and proteins.

PMID- 10968974
TI  - Spinning-frequency-dependent narrowband RF-driven dipolar recoupling
AB  - Dipolar recoupling techniques of homonuclear spin pairs are commonly used for
      distance or orientation measurements in solids. Accurate measurements are
      interfered with by broadening mechanisms. In this publication narrowband RF
      driven dipolar recoupling magnetization exchange experiments are performed as a
      function of the spinning frequency to reduce the effect of zero-quantum T(2)
      relaxation. To enhance the exchange of magnetization between the coupled spins, a
      fixed number of rotor-synchronous pi-pulses are applied at spinning frequencies
      approaching the rotational resonance (R(2)) conditions. The analysis of the
      powder averaged dipolar decay curves of the spin magnetizations as a function of
      the spinning frequency provides a quantitative measure of the dipolar coupling.
      An effective Hamiltonian for this experiment is derived, taking into account all
      chemical shift parameters of the spins. The length of the nbRFDR mixing time and
      the number of rotor cycles per pi-pulse are optimized by numerical simulations
      for sensitive probing of the dipolar coupling strength. The zero-quantum T(2)
      relaxation time can easily be taken into account in the data analysis, because
      the overall exchange time is almost constant in these experiments. Spinning
      frequency-dependent nbRFDR experiments near the m = 1 and m = 2 R(2) condition
      are shown for doubly (13)C-labeled hydroxybutyric acid. Copyright 2000 Academic
      Press.

PMID- 10968975
TI  - Measuring (13)C-(2)D dipolar couplings with a universal REDOR dephasing curve
AB  - A (13)C-observe REDOR experiment is described which allows (13)C-(2)D dipolar
      couplings to be obtained by a universal dipolar dephasing curve. Previous (13)C
      observe REDOR experiments on (13)C-(2)D spin pairs generally relied on numerical
      simulations to obtain the dipolar coupling. The REDOR experiment described in
      this article is based on a deuterium composite pulse, and the data analysis
      eliminates the need for numerical simulations and is the same as the traditional
      REDOR analysis performed on pairs of spin-12 nuclei. Copyright 2000 Academic
      Press.

PMID- 10968976
TI  - Single-coil surface imaging using a radiofrequency field gradient
AB  - A method for in-plane imaging of large objects as compared to the RF coil is
      proposed based on the use of a single specially designed surface coil, without
      using B(0) gradients. A constant B(1) gradient was generated along the main axis
      of a ladder-shaped coil, and RF-encoding along the direction of the gradient made
      it possible to obtain spin-density profiles. Successive acquisitions of profiles
      obtained by translation of the NMR coil resulted in distorted images-due to the
      presence of non-zero gradients perpendicular to the constant gradient-that were
      successfully processed using a mathematical treatment based on linear
      combinations of calculated altered images from single-pixel objects. Copyright
      2000 Academic Press.

PMID- 10968977
TI  - A J-multiplied HMQC (MJ-HMQC) experiment for measuring (3)J(HNHalpha) coupling
      constants.
AB  - The J-multiplied HSQC experiment (MJ-HSQC: S. Heikkinen et al., J. Magn. Reson
      137, 243 (1999)) amplifies J coupling constants m times and allows direct
      observation of the (3)J(HNHalpha) coupling constants of peptides and proteins
      (<10 kDa). The drawbacks to this method are line broadening in the f(1)-dimension
      and lower sensitivity. In the J-multiplied HMQC (MJ-HMQC) experiment described
      here, the PEP-HSQC pulse sequence is replaced by a sensitivity-enhanced HMQC
      section, and the total decay time for the J-coupling and the chemical shift
      evolution is shortened by a period of t(1). This experiment affords narrower
      linewidth and enhances the sensitivity by 34%, on an average of 105 well-isolated
      peaks, when compared with the MJ-HSQC experiment.

PMID- 10968978
TI  - 2J,(3)J-HMBC: A new long-range heteronuclear shift correlation technique capable
      of differentiating (2)J(CH) from (3)J(CH) correlations to protonated carbons
AB  - The development of a series of new, accordion-optimized long-range heteronuclear
      shift correlation techniques has been reported. A further derivative of the
      constant time variable delay introduced in the IMPEACH-MBC experiment, a STAR
      (Selectively Tailored Accordion F(1) Refocusing) operator is described in the
      present report. Incorporation of the STAR operator with the capability of user
      selected homonuclear modulation scaling as in the CIGAR-HMBC experiment, into a
      long-range heteronuclear shift correlation pulse sequence, (2)J,(3)J-HMBC,
      affords for the first time in a proton-detected experiment the means of
      unequivocally differentiating two-bond ((2)J(CH)) from three-bond ((3)J(CH)) long
      range correlations to protonated carbons. Copyright 2000 Academic Press.

PMID- 10968979
TI  - Strange effects of pulse shaping in water presaturation experiments
AB  - During the course of some water presaturation experiments with a shaped pulse
      envelope we observed inverted responses from certain signals flanking the water
      response. This phenomenon did not occur when a rectangular presaturation envelope
      was used. Apparently the leading and trailing edges of the shaped pulse act as
      adiabatic sweeps, causing the coupled magnetizations in question to be spin
      locked. This gives rise to Hartmann-Hahn coherence transfer, and when the spin
      lock duration is equal to 1/(2J) the trajectories are such as to carry these
      magnetization vectors to the -z axis, leading to inverted signals in the final
      spectrum. Copyright 2000 Academic Press.

PMID- 10968980
TI  - A simple method to increase the spectral window for ultra wide NMR spectroscopy

PMID- 10968981
TI  - Cumulant analysis of charge recombination kinetics in bacterial reaction centers
      reconstituted into lipid vesicles.
AB  - The kinetics of charge recombination between the primary photoxidized donor
      (P(+)) and the secondary reduced quinone acceptor (Q(B)(-)) have been studied in
      reaction centers (RCs) from the purple photosynthetic bacterium Rhodobacter
      sphaeroides incorporated into lecithin vesicles containing large ubiquinone pools
      over the temperature range 275 K </= T </= 307 K. To account for the non
      exponential kinetics of P(+) re-reduction observed following a flash, a new
      approach has been developed, based on the following assumptions: 1) the exchange
      of quinone between different vesicles is negligible; 2) the exchange of quinone
      between the Q(B) site of the RC and the quinone pool within each single vesicle
      is faster than the return of the electron from the primary reduced acceptor Q(A)(
      ) to P(+); 3) the size polydispersity of proteoliposomes and the distribution of
      quinone molecules among them result in a quinone concentration distribution
      function, P(Q). The first and second moments of P(Q) have been evaluated from the
      size distribution of proteoliposomes probed by quasi-elastic light scattering
      (mean radius, <R> = (50 +/- 15) nm). Following these premises, we describe the
      kinetics of P(+)Q(B)(-) recombination with a truncated cumulant expansion and
      relate it to P(Q) and to the free energy changes for Q(A)(-)Q(B) --> Q(A)Q(B)(-)
      electron transfer (DeltaG(AB)(o)) and for quinone binding (DeltaG(bind)(o)) at
      Q(B). The model accounts well for the temperature and quinone dependence of the
      charge recombination kinetics, yielding DeltaG(AB)(o) = -7.67 +/- 0.05 kJ mol(-1)
      and DeltaG(bind)(o) = -14.6 +/- 0.6 kJ mol(-1) at 298 K.

PMID- 10968982
TI  - Association entropy in adsorption processes.
AB  - The association of two species to form a bound complex, e.g., the binding of a
      ligand to a protein or the adsorption of a peptide on a lipid membrane, involves
      an entropy loss, reflecting the conversion of free translational and rotational
      degrees of freedom into bound motions. Previous theoretical estimates of the
      standard entropy change in bimolecular binding processes, DeltaS(o), have been
      derived from the root-mean-square fluctuations in protein crystals, suggesting
      DeltaS(o) approximately -50 e.u., i.e., TDeltaS degrees approximately -25 kT = 
      15 kcal/mol. In this work we focus on adsorption, rather than binding processes.
      We first present a simple statistical-thermodynamic scheme for calculating the
      adsorption entropy, including its resolution into translational and rotational
      contributions, using the known distance-orientation dependent binding
      (adsorption) potential. We then utilize this scheme to calculate the free energy
      of interaction and entropy of pentalysine adsorption onto a lipid membrane,
      obtaining TDeltaS(o) approximately -1.7 kT approximately -1.3 kcal/mol. Most of
      this entropy change is due to the conversion of one free translation into a bound
      motion, the rest arising from the confinement of two rotational degrees of
      freedom. The smaller entropy loss in adsorption compared to binding processes
      arises partly because a smaller number of degrees of freedom become restricted,
      but mainly due to the fact that the binding potential is much "softer."

PMID- 10968983
TI  - Switching from simple to complex oscillations in calcium signaling.
AB  - We present a new model for calcium oscillations based on experiments in
      hepatocytes. The model considers feedback inhibition on the initial agonist
      receptor complex by calcium and activated phospholipase C, as well as receptor
      type-dependent self-enhanced behavior of the activated G(alpha) subunit. It is
      able to show simple periodic oscillations and periodic bursting, and it is the
      first model to display chaotic bursting in response to agonist stimulations.
      Moreover, our model offers a possible explanation for the differences in dynamic
      behavior observed in response to different agonists in hepatocytes.

PMID- 10968984
TI  - A kinetic model of vertebrate 20S proteasome accounting for the generation of
      major proteolytic fragments from oligomeric peptide substrates.
AB  - There is now convincing evidence that the proteasome contributes to the
      generation of most of the peptides presented by major histocompatibility complex
      class I molecules. Here we present a model-based kinetic analysis of fragment
      patterns generated by the 20S proteasome from 20 to 40 residues long oligomeric
      substrates. The model consists of ordinary first-order differential equations
      describing the time evolution of the average probabilities with which fragments
      can be generated from a given initial substrate. First-order rate laws are used
      to describe the cleavage of peptide bonds and the release of peptides from the
      interior of the proteasome to the external space. Numerical estimates for the 27
      unknown model parameters are determined across a set of five different proteins
      with known cleavage patterns. Testing the validity of the model by a jack knife
      procedure, about 80% of the observed fragments can be correctly identified,
      whereas the abundance of false-positive classifications is below 10%. From our
      theoretical approach, it is inferred that double-cleavage fragments of length 7
      13 are predominantly cut out in "C-N-order" in that the C-terminus is generated
      first. This is due to striking differences in the further processing of the two
      fragments generated by the first cleavage. The upstream fragment exhibits a
      pronounced tendency to escape from second cleavage as indicated by a large
      release rate and a monotone exponential decline of peptide bond accessibility
      with increasing distance from the first scissile bond. In contrast, the release
      rate of the downstream fragment is about four orders of magnitude lower and the
      accessibility of peptide bonds shows a sharp peak in a distance of about nine
      residues from the first scissile bond. This finding strongly supports the idea
      that generation of fragments with well-defined lengths is favored in that
      temporary immobilization of the downstream fragment after the first cleavage
      renders it susceptible for a second cleavage.

PMID- 10968985
TI  - Model energy landscapes and the force-induced dissociation of ligand-receptor
      bonds.
AB  - We discuss models for the force-induced dissociation of a ligand-receptor bond,
      occurring in the context of cell adhesion or single molecule unbinding force
      measurements. We consider a bond with a structured energy landscape which is
      modeled by a network of force dependent transition rates between intermediate
      states. The behavior of a model with only one intermediate state and a model
      describing a molecular zipper is studied. We calculate the bond lifetime as a
      function of an applied force and unbinding forces under an increasing applied
      load and determine the relationship between both quantities. The dissociation via
      an intermediate state can lead to distinct functional relations of the bond
      lifetime on force. One possibility is the occurrence of three force regimes where
      the lifetime of the bond is determined by different transitions within the energy
      landscape. This case can be related to recent experimental observations of the
      force-induced dissociation of single avidin-biotin bonds.

PMID- 10968986
TI  - Conformational dynamics of a 5S rRNA hairpin domain containing loop D and a
      single nucleotide bulge.
AB  - Molecular modeling and molecular dynamics have been employed to study the
      conformation and flexibility of a 15-nucleotide fragment of the plant 5S rRNA
      containing loop D and a single uridine bulge. Two different model built initial
      structures were used: one with the bulge localized inside the helical stem and
      another with the bulge pointing out from the helix. Several independent 700-ps
      long trajectories in aqueous solution with Na(+) conterions were produced for
      each starting structure. The bulge nucleotide inside the helix stayed in two main
      conformations, both of which affected the geometry of the stem part opposite the
      bulge. When the bulge nucleotide was located outside the helix, we found high
      base mobility and local backbone flexibility. The dynamics of the hydrogen bond
      network and conformational changes from a direct to a water mediated hydrogen
      bond in the sheared G-A basepair in the tetraloop was described. Our results
      correlate with lead ion induced cleavage patterns in 5S rRNA. Sites resistant to
      nonspecific lead cleavage appeared in all our simulations as the most rigid
      fragments independent of the localization of the bulge nucleotide.

PMID- 10968987
TI  - Fluctuations and quality of control in biological cells: zero-order
      ultrasensitivity reinvestigated.
AB  - Living cells differ from most other chemical systems in that they involve
      regulation pathways that depend very nonlinearly on chemical species that are
      present in low copy numbers per cell. This leads to a variety of intracellular
      kinetic phenomena that elude macroscopic modeling, which implicitly assumes that
      cells are infinitely large and fluctuations negligible. It is of particular
      importance to assess how fluctuations affect regulation in cases where precision
      and reliability are required. Here, taking finite cell size and stochastic
      aspects into account, we reinvestigate theoretically the mechanism of zero-order
      ultrasensitivity for covalent modification of target enzymes ( Proc. Natl. Acad.
      Sci. USA. 78:6840-6844). Macroscopically, this mechanism can produce a very sharp
      transition in target concentrations for very small changes in the activity of the
      converter enzymes. This study shows that the transition is much more gradual in a
      finite cell or a population of finite cells. It also demonstrates that the switch
      is exactly analogous to a thermodynamic phase transition and that
      ultrasensitivity is inevitably coupled to random ultravariation. As a
      consequence, the average response in a large population of cells will often be
      much more gradual than predicted from macroscopic descriptions.

PMID- 10968988
TI  - Self-regulation phenomena in bacterial reaction centers. I. General theory.
AB  - A model for light-induced charge separation in a donor-acceptor system of the
      reaction center of photosynthetic bacteria is described. This description is
      predicated on a self-regulation of the flow of photo-activated electrons due to
      self-consistent, slow structural rearrangements of the macromolecule. Effects of
      the interaction between the separated charges and the slow structural modes of
      the biomolecule may accumulate during multiple, sequential charge transfer
      events. This accumulation produces non-linear dynamic effects on system function,
      providing a regulation of the charge separation efficiency. For a biomolecule
      with a finite number of different charge-transfer states, the quasi-stationary
      populations of these states with a localized electron on different cofactors may
      deviate from a Lagmuir law dependence with actinic light intensity. Such
      deviations are predicted by the model to be due to light-induced structural
      changes. The theory of self-regulation developed here assumes that light-induced
      changes in the effective adiabatic potential occur along a slow structural
      coordinate. In this model, a "light-adapted" conformational state appears when
      bifurcation produces a new minimum in the adiabatic potential. In this state, the
      lifetime of the charge-separated state may be quite different from that of the
      "dark-adapted" conformation. The results predicted by this theory agree with
      previously obtained experimental results on photosynthetic reaction centers.

PMID- 10968989
TI  - Quantum-dynamical picture of a multistep enzymatic process: reaction catalyzed by
      phospholipase A(2).
AB  - A quantum-classical molecular dynamics model (QCMD), applying explicit
      integration of the time-dependent Schrodinger equation (QD) and Newtonian
      equations of motion (MD), is presented. The model is capable of describing
      quantum dynamical processes in complex biomolecular systems. It has been applied
      in simulations of a multistep catalytic process carried out by phospholipase A(2)
      in its active site. The process includes quantum-dynamical proton transfer from a
      water molecule to histidine localized in the active site, followed by a
      nucleophilic attack of the resulting OH(-) group on a carbonyl carbon atom of a
      phospholipid substrate, leading to cleavage of an adjacent ester bond. The
      process has been simulated using a parallel version of the QCMD code. The
      potential energy function for the active site is computed using an approximate
      valence bond (AVB) method. The dynamics of the key proton is described either by
      QD or classical MD. The coupling between the quantum proton and the classical
      atoms is accomplished via Hellmann-Feynman forces, as well as the time dependence
      of the potential energy function in the Schrodinger equation (QCMD/AVB model).
      Analysis of the simulation results with an Advanced Visualization System revealed
      a correlated rather than a stepwise picture of the enzymatic process. It is shown
      that an sp(2)--> sp(3) configurational change at the substrate carbonyl carbon is
      mostly responsible for triggering the activation process.

PMID- 10968990
TI  - Structure and hydration of BamHI DNA recognition site: a molecular dynamics
      investigation.
AB  - The results of a 3-ns molecular dynamics simulation of the dodecamer duplex
      d(TATGGATCCATA)(2) recognized by the BamHI endonuclease are presented here. The
      DNA has been simulated as a flexible molecule using an AMBER force field and the
      Ewald summation method, which eliminates the undesired effects of truncation and
      permits evaluation of the full effects of electrostatic forces. The starting B
      conformation evolves toward a configuration quite close to that observed through
      x-ray diffraction in its complex with BamHI. This configuration is fairly stable
      and the Watson-Crick hydrogen bonds are well maintained over the simulation
      trajectory. Hydration analysis indicates a preferential hydration for the
      phosphate rather than for the ester oxygens. Hydration shells in both the major
      and minor groove were observed. In both grooves the C-G pairs were found to be
      more hydrated than A-T pairs. The "spine of hydration" in the minor groove was
      clear. Water residence times are longer in the minor groove than in the major
      groove, although relatively short in both cases. No special long values are
      observed for sites where water molecules were observed by x-ray diffraction,
      indicating that water molecules having a high probability of being located in a
      specific site are also fast-exchanging.

PMID- 10968991
TI  - Inhibition of Ca(2+) sparks by ruthenium red in permeabilized rat ventricular
      myocytes.
AB  - We have compared the effects of the sarcoplasmic reticulum (SR) Ca(2+) release
      inhibitor, ruthenium red (RR), on single ryanodine receptor (RyR) channels in
      lipid bilayers, and on Ca(2+) sparks in permeabilized rat ventricular myocytes.
      Ruthenium red at 5 microM inhibited the open probability (P(o)) of RyRs
      approximately 20-50-fold, without significantly affecting the conductance or mean
      open time of the channel. At the same concentration, RR inhibited the frequency
      of Ca(2+) sparks in permeabilized myocytes by approximately 10-fold, and reduced
      the amplitude of large amplitude events (with most probable localization on the
      line scan) by approximately 3-fold. According to our theoretical simulations,
      performed with a numerical model of Ca(2+) spark formation, this reduction in
      Ca(2+) spark amplitude corresponds to an approximately 4-fold decrease in Ca(2+)
      release flux underlying Ca(2+) sparks. Ruthenium red (5 microM) increased the SR
      Ca(2+) content by approximately 2-fold (from 151 to 312 micromol/l cytosol).
      Considering the degree of inhibition of local Ca(2+) release events, the increase
      in SR Ca(2+) load by RR, and the lack of effects of RR on single RyR open time
      and conductance, we have estimated that Ca(2+) sparks under normal conditions are
      generated by openings of at least 10 single RyRs.

PMID- 10968992
TI  - Quantitative morphodynamics of endothelial cells within confluent cultures in
      response to fluid shear stress.
AB  - To evaluate shear stress-induced effects on cultured cells we have extended the
      mechanical setup of a multichannel in vitro rheological system and developed
      software allowing entire processing control and image data analysis. The values
      of cell motility, degree of orientation (alignment), and cell elongation were
      correlated as a function of time (morphodynamics). Collective and individual
      endothelial cells within confluent cultures displayed a shear stress-dependent
      characteristic phase behavior of the following time course: resting conditions
      (phase I), change of motility (phase II), onset of alignment (phase III), and
      finally cell elongation (phase IV). Especially cell motility was characterized by
      a randomized zigzag movement around mean trajectories (fluctuations) together
      with mean cell locomotion. Onset of shear stress caused a down-regulation of
      fluctuations of 30% within <10 min and simultaneously increased locomotion
      velocities preferring the flow direction (phase II). After a lag period of 10 to
      20 min cells orientated in the direction of flow (phase III) without significant
      cell elongation, which finally occurs within hours (phase IV). These data provide
      first evidence that cells within confluent endothelial monolayers respond to
      shear stress with a characteristic phase behavior.

PMID- 10968993
TI  - Interaction of cationic colloids at the surface of J774 cells: a kinetic
      analysis.
AB  - We have characterized the binding of multilamellar colloids to J774 cells.
      Cationic colloids were shown to bind much more efficiently than neutral ones.
      Particle uptake by cells was followed by flow cytometry and fluorescence
      microscopy. Analysis of the kinetics of uptake of cationic particles indicated
      that binding on the cell surface occurred with two characteristic times. Analysis
      of the dissociation properties allowed discriminating between several alternative
      models for adsorption and led us to propose a mechanism that involved two
      independent classes of binding sites on the cell surface. One class of sites
      appeared to be governed by a classic mass action law describing a binding
      equilibrium. The other sites were populated irreversibly by particles made of 10%
      cationic lipids. This was observed in the absence of endocytosis, under
      conditions where both the equilibrium and the irreversible binding occurred at
      the cell surface. We determined the rate constants for the different steps. We
      found that the reversible association occurred with a characteristic time of the
      order of tens of seconds, whereas the irreversible binding took a hundred times
      longer. The presence of serum proteins in the incubation medium did not
      drastically affect the final uptake of the particles. In contrast, the capture of
      the particles by cells significantly dropped when the fraction of positively
      charged lipids contained in the colloids was decreased from 10% to 5%. Finally,
      the results will be discussed within a comprehensive model where cationic
      particles find labile binding sites in the volume of the pericellular network
      (glycocalyx and extracellular matrix) and less-accessible irreversible binding
      sites at the cell membrane itself.

PMID- 10968994
TI  - Amplitude-dependent spike-broadening and enhanced Ca(2+) signaling in GnRH
      secreting neurons.
AB  - In GnRH-secreting (GT1) neurons, activation of Ca(2+)-mobilizing receptors
      induces a sustained membrane depolarization that shifts the profile of the action
      potential (AP) waveform from sharp, high-amplitude to broad, low-amplitude
      spikes. Here we characterize this shift in the firing pattern and its impact on
      Ca(2+) influx experimentally by using prerecorded sharp and broad APs as the
      voltage-clamp command pulse. As a quantitative test of the experimental data, a
      mathematical model based on the membrane and ionic current properties of GT1
      neurons was also used. Both experimental and modeling results indicated that
      inactivation of the tetrodotoxin-sensitive Na(+) channels by sustained
      depolarization accounted for a reduction in the amplitude of the spike upstroke.
      The ensuing decrease in tetraethylammonium-sensitive K(+) current activation
      slowed membrane repolarization, leading to AP broadening. This change in firing
      pattern increased the total L-type Ca(2+) current and facilitated AP-driven
      Ca(2+) entry. The leftward shift in the current-voltage relation of the L-type
      Ca(2+) channels expressed in GT1 cells allowed the depolarization-induced AP
      broadening to facilitate Ca(2+) entry despite a decrease in spike amplitude. Thus
      the gating properties of the L-type Ca(2+) channels expressed in GT1 neurons are
      suitable for promoting AP-driven Ca(2+) influx in receptor- and non-receptor
      depolarized cells.

PMID- 10968995
TI  - Quantitative analysis of tetrapentylammonium-induced blockade of open N-methyl-D
      aspartate channels.
AB  - The blockade of open N-methyl-d-aspartate (NMDA) channels by tetrapentylammonium
      (TPentA) in acutely isolated rat hippocampal neurons was studied using whole-cell
      patch-clamp techniques. TPentA prevented the closure of the NMDA channel
      following what is known as the foot-in-the-door mechanism. Hooked tail currents
      appearing after termination of the agonist (aspartate) and TPentA coapplication
      were analyzed quantitatively according to the corresponding sequential kinetic
      model. Studies of the hooked tail current amplitude and the degree of the
      stationary current inhibition dependence on the blocker concentration led to a
      new method for estimation of fast foot-in-the-door blocker binding/unbinding rate
      constants. The application of this method to the NMDA channel blockade by TPentA
      allowed finding the values of its binding (1.48 microM(-1)s(-1)) and unbinding
      (14 s(-1)) rate constants. An analysis of the dependence of the electric charge
      carried during the hooked tail current on the blocker concentration led to a new
      method for estimation of the maximum NMDA channel open probability, P(0). The
      value of P(0) found in experiments with TPentA was 0.04.

PMID- 10968996
TI  - Block of sodium channels by divalent mercury: role of specific cysteinyl residues
      in the P-loop region.
AB  - Divalent mercury (Hg(2+)) blocked human skeletal Na(+) channels (hSkM1) in a
      stable dose-dependent manner (K(d) = 0.96 microM) in the absence of reducing
      agent. Dithiothreitol (DTT) significantly prevented Hg(2+) block of hSkM1, and
      Hg(2+) block was also readily reversed by DTT. Both thimerosal and 2,2'
      dithiodipyridine had little effect on hSkM1; however, pretreatment with
      thimerosal attenuated Hg(2+) block of hSkM1. Y401C+E758C rat skeletal muscle
      Na(+) channels (mu1) that form a disulfide bond spontaneously between two
      cysteines at the 401 and 758 positions showed a significantly lower sensitivity
      to Hg(2+) (K(d) = 18 microM). However, Y401C+E758C mu1 after reduction with DTT
      had a significantly higher sensitivity to Hg(2+) (K(d) = 0.36 microM) than wild
      type hSkM1. Mutants C753Amu1 (K(d) = 8.47 microM) or C1521A mu1 (K(d) = 8.63
      microM) exhibited significantly lower sensitivity to Hg(2+) than did wild-type
      hSkM1, suggesting that these two conserved cysteinyl residues of the P-loop
      region may play an important role in the Hg(2+) block of the hSkM1 isoform. The
      heart Na(+) channel (hH1) was significantly more sensitive to low-dose Hg(2+)
      (K(d) = 0.43 microM) than was hSkM1. The C373Y hH1 mutant exhibited higher
      resistance (K(d) = 1.12 microM) to Hg(2+) than did wild-type hH1. In summary,
      Hg(2+) probably inhibits the muscle Na(+) channels at more than one cysteinyl
      residue in the Na(+) channel P-loop region. Hg(2+) exhibits a lower K(d) value
      (<1. 23 microM) for inhibition by forming a sulfur-Hg-sulfur bridge, as compared
      to reaction at a single cysteinyl residue with a higher K(d) value (>8.47 microM)
      by forming sulfur-Hg(+) covalently. The heart Na(+) channel isoform with more
      than two cysteinyl residues in the P-loop region exhibits an extremely high
      sensitivity (K(d) < 0. 43 microM) to Hg(+), accounting for heart-specific high
      sensitivity to the divalent mercury.

PMID- 10968997
TI  - P(3)-[2-(4-hydroxyphenyl)-2-oxo]ethyl ATP for the rapid activation of the
      Na(+),K(+)-ATPase.
AB  - P(3)-[2-(4-hydroxyphenyl)-2-oxo]ethyl ATP (pHP-caged ATP) has been investigated
      for its application as a phototrigger for the rapid activation of electrogenic
      ion pumps. The yield of ATP after irradiation with a XeCl excimer laser (lambda =
      308 nm) was determined at pH 6.0-7.5. For comparison, the photolytic yields of
      P(3)-[1-(2-nitrophenyl)]ethyl ATP (NPE-caged ATP) and P(3)-[1, 2-diphenyl-2
      oxo]ethyl ATP (desyl-caged ATP) were also measured. It was shown that at lambda =
      308 nm pHP-caged ATP is superior to the other caged ATP derivatives investigated
      in terms of yield of ATP after irradiation. Using time-resolved single-wavelength
      IR spectroscopy, we determined a lower limit of 10(6) s(-1) for the rate constant
      of release of ATP from pHP-caged ATP at pH 7.0. Like NPE-caged ATP, pHP-caged ATP
      and desyl-caged ATP bind to the Na(+), K(+)-ATPase and act as competitive
      inhibitors of ATPase function. Using pHP-caged ATP, we investigated the charge
      translocation kinetics of the Na(+),K(+)-ATPase at pH 6.2-7.4. The kinetic
      parameters obtained from the electrical measurements are compared to those
      obtained with a technique that does not require caged ATP, namely parallel
      stopped-flow experiments using the voltage-sensitive dye RH421. It is shown that
      the two techniques yield identical results, provided the inhibitory properties of
      the caged compound are taken into account. Our results demonstrate that under
      physiological (pH 7.0) and slightly basic (pH 7.5) or acidic (pH 6. 0)
      conditions, pHP-caged ATP is a rapid, effective, and biocompatible phototrigger
      for ATP-driven biological systems.

PMID- 10968998
TI  - Sh and eag K(+) channel subunit interaction in frog oocytes depends on level and
      time of expression.
AB  - Subcellular clustering of ion channels critically affects neuronal function.
      Coexpression of Eag and Sh channel subunits in Xenopus oocytes leads to
      accelerated decay of the Sh-like transient K(+) current (Chen, M.-L., T. Hoshi,
      and C.-F. Wu. 1996. Neuron. 17:535-542). We report that such interaction depends
      critically on functional expression level (controlled by RNA injection quantities
      and indicated by current amplitudes) and developmental time after RNA injection.
      The accelerated decay became apparent 3 days after coinjection and increased
      thereafter. This was observed in different ionic conditions and at different
      voltage steps. However, decay was not accelerated at low expression levels,
      either within 1-2 days after injection or with reduced amounts of RNA. With
      sequential RNA injection, preformation of either Eag or Sh channels prevented
      interactions with the other subunit. The carboxyl terminus of Eag was found to be
      involved in accelerating, and in retarding recovery from, N-type inactivation.
      The interaction was reduced upon patch excision in macropatch measurements,
      suggesting involvement of cytosolic factors. We have reproduced the absence of
      interaction between Eag and Sh reported previously within 2 days after RNA
      injection and with low levels of current expression (Tang, C.-Y., C. T.
      Schulteis, R. M. Jimenez, and D. M. Papazian. 1998. Biophys. J. 75:1263-1270).
      Our findings demonstrate that heterologous expression of channels in Xenopus
      oocytes is a dynamic process influenced by cell physiology and development. These
      factors must be considered in interpreting the functional properties of
      heterologously expressed channels.

PMID- 10968999
TI  - MinK endows the I(Ks) potassium channel pore with sensitivity to internal
      tetraethylammonium.
AB  - I(Ks) channels are heteromeric complexes of pore-forming KvLQT1 subunits and pore
      associated MinK subunits. Channels formed only of KvLQT1 subunits vary from I(Ks)
      channels in their gating kinetics, single-channel conductance, and ion
      selectivity. Here we show that I(Ks) channels are more sensitive to blockade by
      internal tetraethylammonium ion (TEA) than KvLQT1 channels. Inhibition by
      internal TEA is shown to proceed by a simple bimolecular interaction in the I(Ks)
      conduction pathway. Application of a noise-variance strategy suggests that MinK
      enhances blockade by increasing the dwell time of TEA on its pore site from
      approximately 70 to 370 micros. Mutation of consecutive residues across the
      single transmembrane segment of MinK identifies positions that alter TEA blockade
      of I(Ks) channels. MinK is seen to determine the pharmacology of I(Ks) channels
      in addition to establishing their biophysical attributes.

PMID- 10969000
TI  - Residues in Na(+) channel D3-S6 segment modulate both batrachotoxin and local
      anesthetic affinities.
AB  - Batrachotoxin (BTX) alters the gating of voltage-gated Na(+) channels and causes
      these channels to open persistently, whereas local anesthetics (LAs) block Na(+)
      conductance. The BTX and LA receptors have been mapped to several common residues
      in D1-S6 and D4-S6 segments of the Na(+) channel alpha-subunit. We substituted
      individual residues with lysine in homologous segment D3-S6 of the rat muscle mu1
      Na(+) channel from F1274 to N1281 to determine whether additional residues are
      involved in BTX and LA binding. Two mutant channels, mu1-S1276K and mu1-L1280K,
      when expressed in mammalian cells, become completely resistant to 5 microM BTX
      during repetitive pulses. The activation and/or fast inactivation gating of these
      mutants is substantially different from that of wild type. These mutants also
      display approximately 10-20-fold reduction in bupivacaine affinity toward their
      inactivated state but show only approximately twofold affinity changes toward
      their resting state. These results demonstrate that residues mu1-S1276 and mu1
      L1280 in D3-S6 are critical for both BTX and LA binding interactions. We propose
      that LAs interact readily with these residues from D3-S6 along with those from D1
      S6 and D4-S6 in close proximity when the Na(+) channel is in its inactivated
      state. Implications of this state-dependent binding model for the S6 alignment
      are discussed.

PMID- 10969001
TI  - Single-channel function of recombinant type 2 inositol 1,4, 5-trisphosphate
      receptor.
AB  - A full-length rat type 2 inositol 1,4,5-trisphosphate (InsP(3)) receptor cDNA
      construct was generated and expressed in COS-1 cells. Targeting of the full
      length recombinant type 2 receptor protein to the endoplasmic reticulum was
      confirmed by immunocytochemistry using isoform specific affinity-purified
      antibodies and InsP(3)R-green fluorescent protein chimeras. The receptor protein
      was solubilized and incorporated into proteoliposomes for functional
      characterization. Single-channel recordings from proteoliposomes fused into
      planar lipid bilayers revealed that the recombinant protein formed InsP(3)- and
      Ca(2+)-sensitive ion channels. The unitary conductance ( approximately 250 pS;
      220/20 mM Cs(+) as charge carrier), gating, InsP(3), and Ca(2+) sensitivities
      were similar to those previously described for the native type 2 InsP(3)R
      channel. However, the maximum open probability of the recombinant channel was
      slightly lower than that of its native counterpart. These data show that our full
      length rat type 2 InsP(3)R cDNA construct encodes a protein that forms an ion
      channel with functional attributes like those of the native type 2 InsP(3)R
      channel. The possibility of measuring the function of single recombinant type 2
      InsP(3)R is a significant step toward the use of molecular tools to define the
      determinants of isoform-specific InsP(3)R function and regulation.

PMID- 10969002
TI  - Tethered polymer-supported planar lipid bilayers for reconstitution of integral
      membrane proteins: silane-polyethyleneglycol-lipid as a cushion and covalent
      linker.
AB  - There is increasing interest in supported membranes as models of biological
      membranes and as a physiological matrix for studying the structure and function
      of membrane proteins and receptors. A common problem of protein-lipid bilayers
      that are directly supported on a hydrophilic substrate is nonphysiological
      interactions of integral membrane proteins with the solid support to the extent
      that they will not diffuse in the plane of the membrane. To alleviate some of
      these problems we have developed a new tethered polymer-supported planar lipid
      bilayer system, which permitted us to reconstitute integral membrane proteins in
      a laterally mobile form. We have supported lipid bilayers on a newly designed
      polyethyleneglycol cushion, which provided a soft support and, for increased
      stability, covalent linkage of the membranes to the supporting quartz or glass
      substrates. The formation and morphology of the bilayers were followed by total
      internal reflection and epifluorescence microscopy, and the lateral diffusion of
      the lipids and proteins in the bilayer was monitored by fluorescence recovery
      after photobleaching. Uniform bilayers with high lateral lipid diffusion
      coefficients (0.8-1.2 x 10(-8) cm(2)/s) were observed when the polymer
      concentration was kept slightly below the mushroom-to-brush transition.
      Cytochrome b(5) and annexin V were used as first test proteins in this system.
      When reconstituted in supported bilayers that were directly supported on quartz,
      both proteins were largely immobile with mobile fractions < 25%. However, two
      populations of laterally mobile proteins were observed in the polymer-supported
      bilayers. Approximately 25% of cytochrome b(5) diffused with a diffusion
      coefficient of approximately 1 x 10(-8) cm(2)/s, and 50-60% diffused with a
      diffusion coefficient of approximately 2 x 10(-10) cm(2)/s. Similarly, one-third
      of annexin V diffused with a diffusion coefficient of approximately 3 x 10(-9)
      cm(2)/s, and two-thirds diffused with a diffusion coefficient of approximately 4
      x 10(-10) cm(2)/s. A model for the interaction of these proteins with the
      underlying polymer is discussed.

PMID- 10969003
TI  - Delay of influenza hemagglutinin refolding into a fusion-competent conformation
      by receptor binding: a hypothesis.
AB  - Two subunits of influenza hemagglutinin (HA), HA1 and HA2, represent one of the
      best-characterized membrane fusion machines. While a low pH conformation of HA2
      mediates the actual fusion, HA1 establishes a specific connection between the
      viral and cell membranes via binding to the sialic acid-containing receptors.
      Here we propose that HA1 may also be involved in modulating the kinetics of HA
      refolding. We hypothesized that binding of the HA1 subunit to its receptor
      restricts the major refolding of the low pH-activated HA to a fusion-competent
      conformation and, in the absence of fusion, to an HA-inactivated state.
      Dissociation of the HA1-receptor connection was considered to be a slow kinetic
      step. To verify this hypothesis, we first analyzed a simple kinetic scheme
      accounting for the stages of dissociation of the HA1/receptor bonds, inactivation
      and fusion, and formulated experimentally testable predictions. Second, we
      verified these predictions by measuring the extent of fusion between HA
      expressing cells and red blood cells. Three experimental approaches based on 1)
      the temporal inhibition of fusion by lysophosphatidylcholine, 2) rapid
      dissociation of the HA1-receptor connections by neuraminidase treatment, and 3)
      substitution of membrane-anchored receptors by a water-soluble sialyllactose all
      provided support for the proposed role of the release of HA1-receptor
      connections. Possible biological implications of this stage in HA refolding and
      membrane fusion are being discussed.

PMID- 10969004
TI  - Modulation of cytochrome C coupling to anionic lipid monolayers by a change of
      the phase state: a combined neutron and infrared reflection study.
AB  - The effect of monolayer domain formation on the electrostatic coupling of
      cytochrome c from the subphase to a monolayer at the air/water interface was
      studied using a combination of neutron reflection (NR) and infrared reflection
      absorption spectroscopy (IRRAS) techniques. The monolayers consisted of a binary
      mixture of the zwitterionic phosphatidylcholine and the anionic
      phosphatidylglycerol. For a monolayer of dipalmitoylphosphatidylcholine (DPPC)
      and dimyristoylphosphatidylglycerol (DMPG, 30 mol%), which exhibits a non-ideal
      mixing of the two lipid components, we observed a significantly higher protein
      coupling to the liquid-condensed phase compared to the liquid-expanded state. In
      contrast, this higher protein binding was not observed when the two lipids had
      identical chain lengths (nearly ideal mixing). Similarly, for an equimolar
      mixture of DPPC and DMPG, we did not observe significant differences in the
      protein binding for the two phase states. The results strongly suggest that the
      domain formation in a condensed monolayer under non-ideal lipid mixing conditions
      is crucial for the cytochrome c binding strength. Furthermore, this study
      demonstrates the significant advantages of gathering information on protein
      monolayer coupling by the combined use of a dedicated IRRAS set-up with the NR
      technique.

PMID- 10969005
TI  - Tunable pH-sensitive liposomes composed of mixtures of cationic and anionic
      lipids.
AB  - The pH-dependent fusion properties of large unilamellar vesicles (LUVs) composed
      of binary mixtures of anionic and cationic lipids have been investigated. It is
      shown that stable LUVs can be prepared from the ionizable anionic lipid
      cholesteryl hemisuccinate (CHEMS) and the permanently charged cationic lipid N,N
      dioleoyl-N, N-dimethylammonium chloride (DODAC) at neutral pH values and that
      these LUVs undergo fusion as the pH is reduced. The critical pH at which fusion
      was observed (pH(f)) was dependent on the cationic lipid-to-anionic lipid ratio.
      LUVs prepared from DODAC/CHEMS mixtures at molar ratios of 0 to 0.85 resulted in
      vesicles with pH(f) values that ranged from pH 4.0 to 6.7, respectively. This
      behavior is consistent with a model in which fusion occurs at pH values such that
      the DODAC/CHEMS LUV surface charge is zero. Related behavior was observed for
      LUVs composed of the ionizable cationic lipid 3alpha-[N-(N',N'
      dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-Chol) and the
      acidic lipid dioleoylphosphatidic acid (DOPA). Freeze-fracture and (31)P NMR
      evidence is presented which indicates that pH-dependent fusion results from a
      preference of mixtures of cationic and anionic lipid for "inverted" nonbilayer
      lipid phases under conditions where the surface charge is zero. It is concluded
      that tunable pH-sensitive LUVs composed of cationic and anionic lipids may be of
      utility for drug delivery applications. It is also suggested that the ability of
      cationic lipids to adopt inverted nonbilayer structures in combination with
      anionic lipids may be related to the ability of cationic lipids to facilitate the
      intracellular delivery of macromolecules.

PMID- 10969006
TI  - Lipoplex formation under equilibrium conditions reveals a three-step mechanism.
AB  - Cellular transfection can be accomplished by the use of synthetic amphiphiles as
      gene carrier system. To understand the mechanism and hence to improve the
      efficiency of transfection, insight into the assembly and properties of the
      amphiphile/gene complex is crucial. Here, we have studied the interaction between
      a plasmid and cationic amphiphiles, using a monolayer technique, and have
      examined complex assembly by atomic force microscopy. The data reveal a three
      step mechanism for complex formation. In a first step, the plasmids, interacting
      with the monolayer, display a strong tendency of orientational ordering.
      Subsequently, individual plasmids enwrap themselves with amphiphile molecules in
      a multilamellar fashion. The size of the complex formed is determined by the
      supercoiled size of the plasmid, and calculations reveal that the plasmid can be
      surrounded by 3 to 5 bilayers of the amphiphile. The eventual size of the
      transfecting complex is finally governed by fusion events between individually
      wrapped amphiphile/DNA complexes. In bulk phase, where complex assembly is
      triggered by mixing amphiphilic vesicles and plasmids, a similar wrapping process
      is observed. However, in this case, imperfections in this process may give rise
      to a partial exposure of plasmids, i.e., part of the plasmid is not covered with
      a layer of amphiphile. We suggest that these exposed sites may act as nucleation
      sites for massive lipoplex clustering, which in turn may affect transfection
      efficiency.

PMID- 10969007
TI  - Surface charge markedly attenuates the nonlamellar phase-forming propensities of
      lipid bilayer membranes: calorimetric and (31)P-nuclear magnetic resonance
      studies of mixtures of cationic, anionic, and zwitterionic lipids.
AB  - The lamellar/nonlamellar phase preferences of lipid model membranes composed of
      mixtures of several cationic lipids with various zwitterionic and anionic
      phospholipids were examined by a combination of differential scanning calorimetry
      and (31)P NMR spectroscopy. All of the cationic lipids utilized in this study
      form only lamellar phases in isolation. Mixtures of these cationic lipids with
      zwitterionic strongly lamellar phase-preferring lipids such as
      phosphatidylcholine form only the lamellar liquid-crystalline phase even at high
      temperatures, as expected. Moreover, mixtures of these cationic lipids with
      strongly nonlamellar phase-preferring zwitterionic lipids such as
      phosphatidylethanolamine exhibit a markedly reduced propensity to form inverted
      nonlamellar phases, again as expected. However, when mixed with anionic lipids
      such as phosphatidylserine, phosphatidylglycerol, cardiolipin, or phosphatidic
      acid, a marked enhancement of nonlamellar phase-forming propensity occurs,
      despite the fact both components of the mixture are nominally lamellar phase
      preferring. An examination of the lamellar/nonlamellar phase transition
      temperatures and the nature of the nonlamellar phases formed, as a function of
      temperature and of the composition of the mixture, indicates that the propensity
      to form inverted nonlamellar phases is maximal in mixtures where the mean surface
      charge of the membrane surface approaches neutrality and decreases markedly with
      increases in the density of positive or negative charge at the membrane surface.
      Moreover, the onset temperatures of the reversed hexagonal phase rise more
      steeply than do those of the inverted cubic phase as the ratio of cationic and
      anionic lipids is varied, suggesting that the formation of inverted hexagonal
      phases is more sensitive to this surface charge effect. These results indicate
      that surface charge per se is a significant and effective modulator of the
      lamellar/nonlamellar phase preferences of membrane lipids and that charged group
      interactions at membrane surfaces may have a major role in regulating this
      particular membrane property.

PMID- 10969008
TI  - Membrane-induced folding of cecropin A.
AB  - Lipid membranes manifest a diverse array of surface forces that can fold and
      orient an approaching protein. To better understand these forces and their
      ability to influence protein function, we have used infrared spectroscopy with
      isotopic editing to characterize the 37-residue membrane-active antimicrobial
      polypeptide cecropin A as it approached, adsorbed onto, and finally penetrated
      various lipid membranes. Intermediate stages in this process were isolated for
      study by the use of internal reflection and Langmuir trough techniques. Results
      indicate that this peptide adopts well-ordered secondary structure while
      superficially adsorbed to a membrane surface. Its conformation is predominantly
      alpha-helical, although some beta structure is likely to be present. The
      longitudinal axis of the helical structure, and the transverse axes of any beta
      structure, are preferentially oriented parallel to the membrane surface. The
      peptide expands the membrane against pressure when it penetrates the membrane
      surface, but its structure and orientation do not change. These observations
      indicate that interactions between the peptide and deeper hydrophobic regions of
      the membrane provide energy to perform thermodynamic work, but separate and
      distinct interactions between the peptide and superficial components of the
      membrane are responsible for peptide folding. These results have broad
      implications for our understanding of the mechanism of action and the specificity
      of these antimicrobial peptides.

PMID- 10969009
TI  - Different sphingolipids show differential partitioning into
      sphingolipid/cholesterol-rich domains in lipid bilayers.
AB  - Two fluorescence-based approaches have been applied to examine the differential
      partitioning of fluorescent phospho- and sphingolipid molecules into sphingolipid
      enriched domains modeling membrane "lipid rafts." Fluorescence-quenching
      measurements reveal that N-(diphenylhexatrienyl)propionyl- (DPH3:0-)-labeled
      gluco- and galactocerebroside partition into sphingolipid-enriched domains in
      sphingolipid/phosphatidylcholine/cholesterol bilayers with substantially higher
      affinity than do analogous sphingomyelin, ceramide, or phosphatidylcholine
      molecules. By contrast, the affinity of sphingomyelin and ceramide for such
      domains is only marginally greater than that of a phosphatidylcholine with
      similar hydrocarbon chains. By using direct measurements of molecular
      partitioning between vesicles of different compositions, we show that the
      relative affinities of different C(6)-NBD- and C(5)-Bodipy-labeled sphingolipids
      for sphingolipid-enriched domains are quantitatively, and in most circumstances
      even qualitatively, quite different from those found for species whose N-acyl
      chains more closely resemble the long saturated chains of cellular sphingolipids.
      These findings lend support in principle to previous suggestions that
      differential partitioning of different sphingolipids into "raft" domains could
      contribute to the differential trafficking of these species in eukaryotic cells.
      However, our findings also indicate that short-chain sphingolipid probes
      previously used to examine this phenomenon are in general ill-suited for such
      applications.

PMID- 10969010
TI  - Effect of fluorine substitution on the interaction of lipophilic ions with the
      plasma membrane of mammalian cells.
AB  - The effects of the anionic tungsten carbonyl complex [W(CO)(5)SC(6)H(5)](-) and
      its fluorinated analog [W(CO)(5)SC(6)F(5)](-) on the electrical properties of the
      plasma membrane of mouse myeloma cells were studied by the single-cell
      electrorotation technique. At micromolar concentrations, both compounds gave rise
      to an additional antifield peak in the rotational spectra of cells, indicating
      that the plasma membrane displayed a strong dielectric dispersion. This means
      that both tungsten derivatives act as lipophilic ions that are able to introduce
      large amounts of mobile charges into the plasma membrane. The analysis of the
      rotational spectra allowed the evaluation not only of the passive electric
      properties of the plasma membrane and cytoplasm, but also of the ion transport
      parameters, such as the surface concentration, partition coefficient, and
      translocation rate constant of the lipophilic anions dissolved in the plasma
      membrane. Comparison of the membrane transport parameters for the two anions
      showed that the fluorine-substituted analog was more lipophilic, but its
      translocation across the plasma membrane was slower by at least one order of
      magnitude than that of the parent hydrogenated anion.

PMID- 10969011
TI  - Conformational selection during weak binding at the actin and myosin interface.
AB  - The molecular mechanism of the powerstroke in muscle is examined by resonance
      energy transfer techniques. Recent models suggesting a pre-cocking of the myosin
      head involving an enormous rotation between the lever arm and the catalytic
      domain were tested by measuring separation distances among myosin subfragment-2,
      the nucleotide site, and the regulatory light chain in the presence of nucleotide
      transition state analogs. Only small changes (<0.5 nm) were detected that are
      consistent with internal conformational changes of the myosin molecule, but not
      with extreme differences in the average lever arm position suggested by some
      atomic models. These results were confirmed by stopped-flow resonance energy
      transfer measurements during single ATP turnovers on myosin. To examine the
      participation of actin in the powerstroke process, resonance energy transfer
      between the regulatory light chain on myosin subfragment-1 and the C-terminus of
      actin was measured in the presence of nucleotide transition state analogs. The
      efficiency of energy transfer was much greater in the presence of ADP-AlF(4), ADP
      BeF(x), and ADP-vanadate than in the presence of ADP or no nucleotide. These data
      detect profound differences in the conformations of the weakly and strongly
      attached cross-bridges that appear to result from a conformational selection that
      occurs during the weak binding of the myosin head to actin.

PMID- 10969012
TI  - The smooth muscle cross-bridge cycle studied using sinusoidal length
      perturbations.
AB  - The mechanical characteristics of smooth muscle can be broadly defined as either
      phasic, or fast contracting, and tonic, or slow contracting (, Pharmacol. Rev.
      20:197-272). To determine if differences in the cross-bridge cycle and/or
      distribution of the cross-bridge states could contribute to differences in the
      mechanical properties of smooth muscle, we determined force and stiffness as a
      function of frequency in Triton-permeabilized strips of rabbit portal vein
      (phasic) and aorta (tonic). Permeabilized muscle strips were mounted between a
      piezoelectric length driver and a piezoresistive force transducer. Muscle length
      was oscillated from 1 to 100 Hz, and the stiffness was determined as a function
      of frequency from the resulting force response. During calcium activation (pCa 4,
      5 mM MgATP), force and stiffness increased to steady-state levels consistent with
      the attachment of actively cycling cross-bridges. In smooth muscle, because the
      cross-bridge states involved in force production have yet to be elucidated, the
      effects of elevation of inorganic phosphate (P(i)) and MgADP on steady-state
      force and stiffness were examined. When portal vein strips were transferred from
      activating solution (pCa 4, 5 mM MgATP) to activating solution with 12 mM P(i),
      force and stiffness decreased proportionally, suggesting that cross-bridge
      attachment is associated with P(i) release. For the aorta, elevating P(i)
      decreased force more than stiffness, suggesting the existence of an attached, low
      force actin-myosin-ADP- P(i) state. When portal vein strips were transferred from
      activating solution (pCa 4, 5 mM MgATP) to activating solution with 5 mM MgADP,
      force remained relatively constant, while stiffness decreased approximately 50%.
      For the aorta, elevating MgADP decreased force and stiffness proportionally,
      suggesting for tonic smooth muscle that a significant portion of force production
      is associated with ADP release. These data suggest that in the portal vein, force
      is produced either concurrently with or after P(i) release but before MgADP
      release, whereas in aorta, MgADP release is associated with a portion of the
      cross-bridge powerstroke. These differences in cross-bridge properties could
      contribute to the mechanical differences in properties of phasic and tonic smooth
      muscle.

PMID- 10969013
TI  - ADP inhibition of myosin V ATPase activity.
AB  - The kinetic mechanism of myosin V is of great interest because recent evidence
      indicates that the two-headed myosin V molecule functions as a processive motor,
      i.e., myosin V is capable of moving along an actin filament for many catalytic
      cycles of the motor without dissociating. Three recent publications assessing the
      kinetics of single-headed myosin V provide different conclusions regarding the
      mechanism, particularly the rate-limiting step of the cycle. One study (, Proc.
      Natl. Acad. Sci. USA. 96:13726-13731) identifies ADP release as the rate-limiting
      step and provides a kinetic explanation for myosin V processivity. The others (,
      J. Biol. Chem. 274:27448-27456;, J. Biol. Chem. 275:4329-4335) do not identify
      the rate-limiting step but conclude that it is not ADP release. We show
      experimental and simulated data demonstrating that the inconsistencies in the
      reports may be due to difficulties in the measurement of the steady-state ATPase
      rate. Under standard assay conditions, ADP competes with ATP, resulting in
      product inhibition of the ATPase rate. This presents technical problems in
      analyzing and interpreting the kinetics of myosin V and likely of other members
      of the myosin family with high ADP affinities.

PMID- 10969014
TI  - Shear-induced assembly of lambda-phage DNA.
AB  - Recombinant DNA technology, which is based on the assembly of DNA fragments,
      forms the backbone of biological and biomedical research. Here we demonstrate
      that a uniform shear flow can induce and control the assembly of lambda-phage DNA
      molecules: increasing shear rates form integral DNA multimers of increasing
      molecular weight. Spontaneous assembly and grouping of end-blunted lambda-phage
      DNA molecules are negligible. It is suggested that shear-induced DNA assembly is
      caused by increasing the probability of contact between molecules and by
      stretching the molecules, which exposes the cohesive ends of the otherwise
      undeformed lambda-phage DNA molecules. We apply this principle to enhance the
      kinetics and extent of DNA concatenation in the presence of ligase. This novel
      approach to controlled DNA assembly could form the basis for improved approaches
      to gene-chip and recombinant DNA technologies and provide new insight into the
      rheology of associating polymers.

PMID- 10969015
TI  - On the truncation of long-range electrostatic interactions in DNA.
AB  - Long-range interactions are known to play an important role in highly polar
      biomolecules like DNA. In molecular dynamics simulations of nucleic acids and
      proteins, an accurate treatment of the long-range interactions are crucial for
      achieving stable nanosecond trajectories. In this report, we evaluate the
      structural and dynamic effects on a highly charged oligonucleotide in aqueous
      solution from different long-range truncation methods. Two group-based truncation
      methods, one with a switching function and one with a force-switching function
      were found to fail to give accurate stable trajectories close to the crystal
      structure. For these group-based truncation methods, large root mean square (rms)
      deviations from the initial structure were obtained and severe distortions of the
      oligonucleotide were observed. Another group-based truncation scheme, which used
      an abrupt truncation at 8. 0 A or at 12.0 A was also investigated. For the short
      cutoff distance, the conformations deviated far away from the initial structure
      and were significantly distorted. However, for the longer cutoff, where all
      necessary electrostatic interactions were included, the trajectory was quite
      stable. For the particle mesh Ewald (PME) truncation method, a stable DNA
      simulation with a heavy atom rms deviation of 1.5 A was obtained. The atom-based
      truncation methods also resulted in stable trajectories, according to the rms
      deviation from the initial B-DNA structure, of between 1.5 and 1.7 A for the
      heavy atoms. In these stable simulations, the heavy atom rms deviations were
      approximately 0.6-1.0 A lower for the bases than for the backbone. An increase of
      the cutoff radius from 8 to 12 A decreased the rms deviation by approximately 0.2
      A for the atom-based truncation method with a force-shifting function, but
      increased the computational time by a factor of 2. Increasing the cutoff from 12
      to 18 A for the atom-based truncation method with a force-shifting function
      requires 2-3 times more computational time, but did not significantly change the
      rms deviation. Similar rms deviations from the initial structure were found for
      the atom-based method with a force-shifting function and for the PME method. The
      computational cost was longer for the PME method with a cutoff of 12. 0 A for the
      direct space nonbonded calculations than for the atom-based truncation method
      with a force-shifting function and a cutoff of 12.0 A. If a nonperiodic boundary,
      e.g., a spherical boundary, was used, a considerable speedup could be achieved.
      From the rms fluctuations, the terminal nucleotides and especially the cytidines
      were found to be more flexible than the nonterminal nucleotides. The B-DNA form
      of the oligonucleotide was maintained throughout the simulations and is judged to
      depend on the parameters of the energy function and not on the truncation method
      used to handle the long-range electrostatic interactions. To perform accurate and
      stable simulations of highly charged biological macromolecules, we recommend that
      the atom-based force-shift method or the PME method should be used for the long
      range electrostatics interactions.

PMID- 10969016
TI  - Competition-integration of blue and orange stimuli in Halobacterium salinarum
      cannot occur solely in SRI photoreceptor.
AB  - Experiments on the integration of blue and orange stimuli in Halobacterium
      salinarum were performed by using different combinations of blue and orange
      steps. The results show that the prevalence of the blue stimulus over the orange
      one depends on both the blue and the orange light intensities. A quantitative
      analysis of the current hypotheses on the phototransduction of orange and UV-blue
      light stimuli is presented, showing that the balancing between the two
      antagonistic stimuli should depend only on the intensity of the blue stimulus and
      not on that of the orange one, provided that the combination of the two stimuli
      occurs linearly at the photoreceptor stage. We conclude that blue and orange
      stimuli elicit distinct intracellular signals whose integration occurs downstream
      of the photoreceptor.

PMID- 10969017
TI  - High-pressure and stark hole-burning studies of chlorosome antennas from
      Chlorobium tepidum.
AB  - Results from high-pressure and Stark hole-burning experiments on isolated
      chlorosomes from the green sulfur bacterium Chlorobium tepidum are presented, as
      well as Stark hole-burning data for bacteriochlorophyll c (BChl c) monomers in a
      poly(vinyl butyral) copolymer film. Large linear pressure shift rates of -0.44
      and -0.54 cm(-1)/MPa were observed for the chlorosome BChl c Q(y)-band at 100 K
      and the lowest Q(y)-exciton level at 12 K, respectively. It is argued that
      approximately half of the latter shift rate is due to electron exchange coupling
      between BChl c molecules. The similarity between the above shift rates and those
      observed for the B875 and B850 BChl a rings of the light-harvesting complexes of
      purple bacteria is emphasized. For BChl c monomer, fDeltamu++ = 0.35 D, where
      Deltamu+ is the dipole moment change for the Q(y) transition and f is the local
      field correction factor. The data establish that Deltamu+ is dominated by the
      matrix-induced contribution. The change in polarizability (Deltaalpha) for the
      Q(y) transition of the BChl c monomer is estimated at 19 A(3), which is
      essentially identical to that of the Chl a monomer. Interestingly, no Stark
      effects were observed for the lowest exciton level of the chlorosomes (maximum
      Stark field of 10(5) V/cm). Possible explanations for this are given, and these
      include consideration of structural models for the chlorosome BChl c aggregates.

PMID- 10969018
TI  - Ultrafast primary processes in PS I from Synechocystis sp. PCC 6803: roles of
      P700 and A(0).
AB  - The excitation transport and trapping kinetics of core antenna-reaction center
      complexes from photosystem I of wild-type Synechocystis sp. PCC 6803 were
      investigated under annihilation-free conditions in complexes with open and closed
      reaction centers. For closed reaction centers, the long-component decay
      associated spectrum (DAS) from global analysis of absorption difference spectra
      excited at 660 nm is essentially flat (maximum amplitude <10(-5) absorbance
      units). For open reaction centers, the long-time spectrum (which exhibits
      photobleaching maxima at approximately 680 and 700 nm, and an absorbance feature
      near 690 nm) resembles one previously attributed to (P700(+) - P700). For
      photosystem I complexes excited at 660 nm with open reaction centers, the
      equilibration between the bulk antenna and far-red chlorophylls absorbing at
      wavelengths >700 nm is well described by a single DAS component with lifetime 2.3
      ps. For closed reaction centers, two DAS components (2.0 and 6.5 ps) are required
      to fit the kinetics. The overall trapping time at P700 ( approximately 24 ps) is
      very nearly the same in either case. Our results support a scenario in which the
      time constant for the P700 --> A(0) electron transfer is 9-10 ps, whereas the
      kinetics of the subsequent A(0) --> A(1) electron transfer are still unknown.

PMID- 10969019
TI  - Significance of a two-domain structure in subunits of phycobiliproteins revealed
      by the normal mode analysis.
AB  - Phycobiliproteins are basic building blocks of phycobilisomes, a supra-molecular
      assembly for the light-capturing function of photosynthesis in cyanobacteria and
      red algae. One functional form of phycobiliproteins is a trimeric form consisting
      of three identical units having C(3) symmetry, with each unit composed of two
      kinds of subunits, the alpha-subunit and beta-subunit. These subunits have
      similar chain folds and can be divided into either globin-like or X-Y helices
      domains. We studied the significance of this two-domain structure for their
      assembled structures and biological function (light-absorption) using a normal
      mode analysis to investigate dynamic aspects of their three-dimensional
      structures. We used C-phycocyanin (C-PC) as an example, and focused on the
      interactions between the two domains. The normal mode analysis was carried out
      for the following two cases: 1) the whole subunit, including the two domains; and
      2) the globin-like domain alone. By comparing the dynamic properties, such as
      correlative movements between residues and the fluctuations of individual
      residues, we found that the X-Y helices domain plays an important role not only
      in the C(3) symmetry assemblies of the subunits in phycobiliproteins, but also in
      stabilizing the light absorption property by suppressing the fluctuation of the
      specific Asp residues near the chromophore. Interestingly, the conformation of
      the X-Y helices domain corresponds to that of a module in pyruvate phosphate
      dikinase (PPDK). The module in PPDK is involved in the interactions of two
      domains, just as the X-Y helices domain is involved in the interactions of two
      subunits. Finally, we discuss the mechanical construction of the C-PC subunits
      based on the normal mode analysis.

PMID- 10969020
TI  - Homology modeling and characterization of IgE binding epitopes of mountain cedar
      allergen Jun a 3.
AB  - The Jun a 3 protein from mountain cedar (Juniperus ashei) pollen, a member of
      group 5 of the family of plant pathogenesis-related proteins (PR-proteins),
      reacts with serum IgE from patients with cedar hypersensitivity. We used the
      crystal structures of two other proteins of this group, thaumatin and an
      antifungal protein from tobacco, both approximately 50% identical in sequence to
      Jun a 3, as templates to build homology models for the allergen. The in-house
      programs EXDIS and FANTOM were used to extract distance and dihedral angle
      constraints from the Protein Data Bank files and determine energy-minimized
      structures. The mean backbone deviations for the energy-refined model structures
      from either of the templates is <1 A, their conformational energies are low, and
      their stereochemical properties (determined with PROCHECK) are acceptable. The
      circular dichroism spectrum of Jun a 3 is consistent with the postulated beta
      sheet core. Tryptic fragments of Jun a 3 that reacted with IgE from allergic
      patients all mapped to one helical/loop surface of the models. The Jun a 3 models
      have features common to aerosol allergens from completely different protein
      families, suggesting that tertiary structural elements may mediate the triggering
      of an allergic response.

PMID- 10969021
TI  - High apparent dielectric constants in the interior of a protein reflect water
      penetration.
AB  - A glutamic acid was buried in the hydrophobic core of staphylococcal nuclease by
      replacement of Val-66. Its pK(a) was measured with equilibrium thermodynamic
      methods. It was 4.3 units higher than the pK(a) of Glu in water. This increase
      was comparable to the DeltapK(a) of 4.9 units measured previously for a lysine
      buried at the same location. According to the Born formalism these DeltapK(a) are
      energetically equivalent to the transfer of a charged group from water to a
      medium of dielectric constant of 12. In contrast, the static dielectric constants
      of dry protein powders range from 2 to 4. In the crystallographic structure of
      the V66E mutant, a chain of water molecules was seen that hydrates the buried Glu
      66 and links it with bulk solvent. The buried water molecules have never
      previously been detected in >20 structures of nuclease. The structure and the
      measured energetics constitute compelling and unprecedented experimental evidence
      that solvent penetration can contribute significantly to the high apparent
      polarizability inside proteins. To improve structure-based calculations of
      electrostatic effects with continuum methods, it will be necessary to learn to
      account quantitatively for the contributions by solvent penetration to dielectric
      effects in the protein interior.

PMID- 10969022
TI  - Effects of high pressure on solvent isotope effects of yeast alcohol
      dehydrogenase.
AB  - The effect of pressure on the capture of a substrate alcohol by yeast alcohol
      dehydrogenase is biphasic. Solvent isotope effects accompany both phases and are
      expressed differently at different pressures. These differences allow the
      extraction of an inverse intrinsic kinetic solvent isotope effect of 1.1 (i.e.,
      (D(2(O)))V/K = 0.9) accompanying hydride transfer and an inverse equilibrium
      solvent isotope effect of 2.6 (i.e., (D(2(O)))K(s) = 0.4) accompanying the
      binding of nucleotide, NAD(+). The value of the kinetic effect is consistent with
      a reactant-state E-NAD(+)-Zn-OH(2) having a fractionation factor of phi
      approximately 0.5 for the zinc-bound water in conjunction with a transition-state
      proton exiting a low-barrier hydrogen bond with a fractionation factor between
      0.6 and 0.9. The value of the equilibrium effect is consistent with restrictions
      of torsional motions of multiple hydrogens of the enzyme protein during the
      conformational change that accompanies the binding of NAD(+). The absence of
      significant commitments to catalysis accompanying the kinetic solvent isotope
      effect means that this portion of the proton transfer occurs in the same reactive
      step as hydride transfer in a concerted chemical mechanism. The success of this
      analysis suggests that future measurements of solvent isotope effects as a
      function of pressure, in the presence of moderate commitments to catalysis, may
      yield precise estimates of intrinsic solvent isotope effects that are not fully
      expressed on capture at atmospheric pressure.

PMID- 10969023
TI  - Structural equilibrium fluctuations in mesophilic and thermophilic alpha-amylase.
AB  - By comparing a mesophilic alpha-amylase with its thermophilic homolog, we
      investigated the relationship between thermal stability and internal equilibrium
      fluctuations. Fourier transform infrared spectroscopy monitoring
      hydrogen/deuterium (H/D) exchange kinetics and incoherent neutron scattering
      measuring picosecond dynamics were used to study dynamic features of the folded
      state at room temperature. Fairly similar rates of slowly exchanging amide
      protons indicate about the same free energy of stabilization DeltaG(stab) for
      both enzymes at room temperature. With respect to motions on shorter time scales,
      the thermophilic enzyme is characterized by an unexpected higher structural
      flexibility as compared to the mesophilic counterpart. In particular, the
      picosecond dynamics revealed a higher degree of conformational freedom for the
      thermophilic alpha-amylase. The mechanism proposed for increasing thermal
      stability in the present case is characterized by entropic stabilization and by
      flattening of the curvature of DeltaG(stab) as a function of temperature.

PMID- 10969024
TI  - Salt effects on ionization equilibria of histidines in myoglobin.
AB  - The salt dependence of histidine pK(a) values in sperm whale and horse myoglobin
      and in histidine-containing peptides was measured by (1)H-NMR spectroscopy.
      Structure-based pK(a) calculations were performed with continuum methods to test
      their ability to capture the effects of solution conditions on pK(a) values. The
      measured pK(a) of most histidines, whether in the protein or in model compounds,
      increased by 0.3 pH units or more between 0.02 M and 1.5 M NaCl. In myoglobin two
      histidines (His(48) and His(36)) exhibited a shallower dependence than the
      average, and one (His(113)) showed a steeper dependence. The (1)H-NMR data
      suggested that the salt dependence of histidine pK(a) values in the protein was
      determined primarily by the preferential stabilization of the charged form of
      histidine with increasing salt concentrations rather than by screening of
      electrostatic interactions. The magnitude and salt dependence of interactions
      between ionizable groups were exaggerated in pK(a) calculations with the finite
      difference Poisson-Boltzmann method applied to a static structure, even when the
      protein interior was treated with arbitrarily high dielectric constants.
      Improvements in continuum methods for calculating salt effects on pK(a) values
      will require explicit consideration of the salt dependence of model compound
      pK(a) values used for reference in the calculations.

PMID- 10969025
TI  - Actin dynamics at the living cell submembrane imaged by total internal reflection
      fluorescence photobleaching.
AB  - Although reversible chemistry is crucial to dynamical processes in living cells,
      relatively little is known about relevant chemical kinetic rates in vivo. Total
      internal reflection/fluorescence recovery after photobleaching (TIR/FRAP), an
      established technique previously demonstrated to measure reversible biomolecular
      kinetic rates at surfaces in vitro, is extended here to measure reversible
      biomolecular kinetic rates of actin at the cytofacial (subplasma membrane)
      surface of living cells. For the first time, spatial imaging (with a charge
      coupled device camera) is used in conjunction with TIR/FRAP. TIR/FRAP imaging
      produces both spatial maps of kinetic parameters (off-rates and mobile fractions)
      and estimates of kinetic correlation distances, cell-wide kinetic gradients, and
      dependences of kinetic parameters on initial fluorescence intensity. For
      microinjected rhodamine actin in living cultured smooth muscle (BC3H1) cells, the
      unbinding rate at or near the cytofacial surface of the plasma membrane (averaged
      over the entire cell) is measured at 0.032 +/- 0.007 s(-1). The corresponding
      rate for actin marked by microinjected rhodamine phalloidin is very similar,
      0.033 +/- 0.013 s(-1), suggesting that TIR/FRAP is reporting the dynamics of
      entire filaments or protofilaments. For submembrane fluorescence-marked actin,
      the intensity, off-rate, and mobile fraction show a positive correlation over a
      characteristic distance of 1-3 microm and a negative correlation over larger
      distances greater than approximately 7-14 microm. Furthermore, the kinetic
      parameters display a statistically significant cell-wide gradient, with the cell
      having a "fast" and "slow" end with respect to actin kinetics.

PMID- 10969026
TI  - Domain motions of EF-G bound to the 70S ribosome: insights from a hand-shaking
      between multi-resolution structures.
AB  - Molecular modeling and information processing techniques were combined to refine
      the structure of translocase (EF-G) in the ribosome-bound form against data from
      cryoelectron microscopy (cryo-EM). We devised a novel multi-scale refinement
      method based on vector quantization and force-field methods that gives excellent
      agreement between the flexibly docked structure of GDP. EF-G and the cryo-EM
      density map at 17 A resolution. The refinement reveals a dramatic "induced fit"
      conformational change on the 70S ribosome, mainly involving EF-G's domains III,
      IV, and V. The rearrangement of EF-G's structurally preserved regions, mediated
      and guided by flexible linkers, defines the site of interaction with the GTPase
      associated center of the ribosome.

PMID- 10969027
TI  - Molecular belt models for the apolipoprotein A-I Paris and Milano mutations.
AB  - Models for the binding of the 200-residue carboxy-terminal domain of two mutants
      of apolipoprotein A-I (apo A-I), apo A-I(R173C)(Milano) and apo A
      I(R151C)(Paris), to lipid in discoidal high-density lipoprotein (HDL) particles
      are presented. In both models, two monomers of the mutant apo A-I molecule bind
      to lipid in an antiparallel manner, with the long axes of their helical repeats
      running perpendicular to the normal of the lipid bilayer to form a single
      disulfide-linked homodimer. The overall structures of the models of these two
      mutants are very similar, differing only in helix-helix registration. Thus these
      models are consistent with experimental observations that reconstituted HDL
      particles containing apo A-I(Milano) and apo A-I(Paris) are very similar in
      diameter to reconstituted HDL particles containing wild-type apo A-I, and they
      support the belief that apo A-I binds to lipid in discoidal HDL particles via the
      belt conformation.

PMID- 10969028
TI  - Mining the myocardium with macrophage drills: A novel mechanism for
      revascularization.

PMID- 10969029
TI  - Vascular control during pregnancy: extending experimental findings to humans.

PMID- 10969030
TI  - Role of gap junctions in cardiac conduction and development: insights from the
      connexin knockout mice.

PMID- 10969031
TI  - Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha
      tocopherol (vitamin E).
AB  - The premise that oxidative stress, among several other factors, plays an
      important role in atherogenesis implies that the development and progression of
      atherosclerosis can be inhibited by antioxidants. In this minireview we discuss
      several mechanisms by which the antioxidants ascorbate (vitamin C) and alpha
      tocopherol (vitamin E) may protect against atherosclerosis. These mechanisms
      include inhibition of LDL oxidation and inhibition of leukocyte adhesion to the
      endothelium and vascular endothelial dysfunction. Overall, ascorbate appears to
      be more effective than alpha-tocopherol in mitigating these pathophysiological
      processes, most likely as a result of its abilities to effectively scavenge a
      wide range of reactive oxygen and nitrogen species and to regenerate alpha
      tocopherol, and possibly tetrahydrobiopterin, from its radical species. In
      contrast, alpha-tocopherol can act either as an antioxidant or a pro-oxidant to
      inhibit or facilitate, respectively, lipid peroxidation in LDL. However, this pro
      oxidant activity of alpha-tocopherol is prevented by ascorbate acting as a
      coantioxidant. Therefore, an optimum vitamin C intake or body status may help
      protect against atherosclerosis and its clinical sequelae, whereas vitamin E may
      only be effective in combination with vitamin C.

PMID- 10969032
TI  - Retinoids: versatile biological response modifiers of vascular smooth muscle
      phenotype.

PMID- 10969033
TI  - Development of a smooth muscle-targeted cre recombinase mouse reveals novel
      insights regarding smooth muscle myosin heavy chain promoter regulation.
AB  - The use of genetically modified mice has been an important model system to study
      gene function in cardiovascular development and under pathophysiological
      conditions. Although conventional gene knockout studies have provided important
      insights into gene function in the cardiovascular system, they may be limited by
      upregulation of compensatory pathways and the inability to differentiate direct
      versus indirect functions in vivo. As a first step in developing systems that can
      target gene activation or inactivation specifically to smooth muscle cells
      (SMCs), we coupled the smooth muscle myosin heavy chain (SMMHC) promoter to the
      cre recombinase gene and generated transgenic mice that express cre in SMCs. In
      addition, we used these mice to address whether the heterogeneous staining
      observed in SMMHC-LacZ mice was due to subsets of SMCs that required different
      regulatory cassettes of the promoter or if it reflected episodic expression of
      the transgene. To address both the feasibility of SMC targeting and the apparent
      heterogeneous expression, we bred SMMHC-cre mice to indicator mice containing a
      cre-activated LacZ gene. Results showed high-level expression in SMCs at various
      embryonic time points and in adult tissues. Because breeding of SMMHC-cre mice to
      an indicator line provided an integration of cre activity over time, results of
      this study revealed that expression of the SMMHC promoter fragment more closely
      resembled the expression of the endogenous gene, both with respect to the onset
      of activation during development and uniformity of staining among individual
      cells within tissues. Overall, these mice will provide a powerful tool to
      researchers to study gene function in vascular development/disease by using
      cre/lox technology to direct smooth muscle-specific gene activation or
      inactivation in vivo.

PMID- 10969034
TI  - Tie2 receptor expression is stimulated by hypoxia and proinflammatory cytokines
      in human endothelial cells.
AB  - The tyrosine kinase receptor Tie2 (also known as Tek) plays an important role in
      the development of the embryonic vasculature and persists in adult endothelial
      cells (ECs). Tie2 was shown to be upregulated in tumors and skin wounds, and its
      ligands angiopoietin-1 and -2, although they are not directly mitogenic, modulate
      neovascularization. To gain further insight into the regulation of Tie2, we have
      studied the effect of hypoxia and inflammatory cytokines, two conditions
      frequently associated with neoangiogenic processes, on Tie2 expression in human
      ECs. Exposure to 1% O(2) led to a time-dependent significant rise of Tie2 protein
      levels in human coronary microvascular endothelial cells (HCMECs) and dermal
      microvascular ECs (HMEC-1) (3.2- and 2.5-fold within 24 hours), which was
      reversible after reoxygenation, and induced a less marked increase in human
      umbilical vein ECs (HUVECs; 1.7-fold). Hypoxia-conditioned medium and D
      deoxyglucose did not change Tie2 expression, but desferrioxamine and cobalt,
      which are known to mimic hypoxia-sensing mechanisms, induced Tie2 at ambient
      oxygen tensions. Tumor necrosis factor-alpha induced Tie2 in a time- and dose
      dependent fashion in all 3 EC types (HUVEC, 2.3-fold; HMEC-1, 2. 8-fold; and
      HCMEC, 3.0-fold; 10 ng/mL, 24 hours). Enhanced expression was also found after
      exposure to interleukin-1beta (1 ng/mL). Changes in Tie2 protein levels were
      paralleled by changes in mRNA expression. In accordance with these in vitro
      findings, immunohistochemistry revealed focal upregulation of Tie2 in capillaries
      at the border of infarcted human and rat myocardium. In conclusion, the data show
      that hypoxia and inflammatory cytokines upregulate Tie2, which may contribute to
      the angiogenic response in ischemic tissues.

PMID- 10969035
TI  - Contribution of monocytes/macrophages to compensatory neovascularization: the
      drilling of metalloelastase-positive tunnels in ischemic myocardium.
AB  - In a transgenic model of ischemic cardiomyopathy in which monocytes are attracted
      to the myocardium by the targeted overexpression of monocyte chemoattractant
      protein-1 (MCP-1), we have observed the presence of endothelial NO synthase and
      platelet endothelial cell adhesion molecule-1-negative tunnels, occasionally
      containing blood-derived cells, that probe the cardiac tissue.
      Immunohistochemical data show that monocytes/macrophages (MCs/Mphs) drill tunnels
      using the broad-spectrum mouse macrophage metalloelastase. 5-Bromo-2'
      deoxyuridine incorporation and neo-endothelial markers present in the
      microvasculature of MCP-1 mouse hearts suggest an active angiogenic process.
      Further studies will be required to establish that the MC-/Mph-drilled tunnels
      evolve to become capillaries, connected to the existing vessels and colonized by
      circulating endothelial cell progenitors. This possibility is supported by the
      availability of these cells, which is demonstrated by cell tagging with beta
      galactosidase placed under an active endothelial Tie-2 promoter. This phenomenon
      might represent another mechanism, in addition to the secretion of the angiogenic
      factors, by which MCs/MPhs may participate in the elaboration of new blood
      vessels in adult tissues.

PMID- 10969036
TI  - Fluid shear stress activates Ca(2+) influx into human endothelial cells via P2X4
      purinoceptors.
AB  - Ca(2+) signaling plays an important role in endothelial cell (EC) responses to
      shear stress generated by blood flow. Our previous studies demonstrated that
      bovine fetal aortic ECs showed a shear stress-dependent Ca(2+) influx when
      exposed to flow in the presence of extracellular ATP. However, the molecular
      mechanisms of this process, including the ion channels responsible for the Ca(2+)
      response, have not been clarified. Here, we demonstrate that P2X4 purinoceptors,
      a subtype of ATP-operated cation channels, are involved in the shear stress
      mediated Ca(2+) influx. Human umbilical vein ECs loaded with the Ca(2+) indicator
      Indo-1/AM were exposed to laminar flow of Hanks' balanced salt solution at
      various concentrations of ATP, and changes in [Ca(2+)](i) were monitored with
      confocal laser scanning microscopy. A stepwise increase in shear stress elicited
      a corresponding stepwise increase in [Ca(2+)](i) at 250 nmol/L ATP. The shear
      stress-dependent increase in [Ca(2+)](i) was not affected by phospholipase C
      inhibitor (U-73122) but disappeared after the chelation of extracellular Ca(2+)
      with EGTA, indicating that the Ca(2+) increase was due to Ca(2+) influx.
      Antisense oligonucleotides designed to knockout P2X4 expression abolished the
      shear stress-dependent Ca(2+) influx seen at 250 nmol/L ATP in human umbilical
      vein ECs. Human embryonic kidney 293 cells showed no Ca(2+) response to flow at 2
      micromol/L ATP, but when transfected with P2X4 cDNA, they began to express P2X4
      purinoceptors and to show shear stress-dependent Ca(2+) influx. P2X4
      purinoceptors may have a "shear-transducer" property through which shear stress
      is perceived directly or indirectly and transmitted into the cell interior via
      Ca(2+) signaling.

PMID- 10969037
TI  - Treatment with dimethylthiourea prevents left ventricular remodeling and failure
      after experimental myocardial infarction in mice: role of oxidative stress.
AB  - Oxidative stress might play an important role in the progression of left
      ventricular (LV) remodeling and failure that occur after myocardial infarction
      (MI). We determined whether reactive oxygen species (ROS) are increased in the LV
      remodeling and failure in experimental MI with the use of electron spin resonance
      spectroscopy and whether the long-term administration of dimethylthiourea (DMTU),
      hydroxyl radical (.OH) scavenger, could attenuate these changes. We studied 3
      groups of mice: sham-operated (sham), MI, and MI animals that received DMTU
      (MI+DMTU). Drugs were administered to the animals daily via intraperitoneal
      injection for 4 weeks.OH was increased in the noninfarcted myocardium from MI
      animals, which was abolished in MI+DMTU. Fractional shortening was depressed by
      65%, LV chamber diameter was increased by 53%, and the thickness of noninfarcted
      myocardium was increased by 37% in MI. MI+DMTU animals had significantly better
      LV contractile function and smaller increases in LV chamber size and hypertrophy
      than MI animals. Changes in myocyte cross-sectional area determined with LV mid
      free wall specimens were concordant with the wall thickness data. Collagen volume
      fraction of the noninfarcted myocardium showed significant increases in the MI,
      which were also attenuated with DMTU. Myocardial matrix metalloproteinase-2
      activity, measured with gelatin zymography, was increased with MI after 7 and 28
      days, which was attenuated in MI+DMTU. Thus, the attenuation of increased
      myocardial ROS and metalloproteinase activity with DMTU may contribute, at least
      in part, to its beneficial effects on LV remodeling and failure. Therapies
      designed to interfere with oxidative stress might be beneficial to prevent
      myocardial failure.

PMID- 10969038
TI  - Abnormal cardiac conduction and morphogenesis in connexin40 and connexin43 double
      deficient mice.
AB  - Connexin40-deficient (Cx40(-/-)/Cx43(+/+)) and connexin43-heterozygous knockout
      mice (Cx40(+/+)/Cx43(+/-)) are viable but show cardiac conduction abnormalities.
      The ECGs of adult double heterozygous animals (Cx40(+/-)/Cx43(+/-)) suggest
      additive effects of Cx40 and Cx43 haploinsufficiency on ventricular, but not on
      atrial, conduction. We also observed additive effects of both connexins on
      cardiac morphogenesis. Approximately half of the Cx40(-/-)/Cx43(+/+) embryos died
      during the septation period, and an additional 16% died after birth. The majority
      of the latter mice had cardiac hypertrophy in conjunction with common
      atrioventricular junction or a ventricular septal defect. All Cx40(-/-)/Cx43(+/-)
      progeny exhibited cardiac malformations and died neonatally. The most frequent
      defect was common atrioventricular junction with abnormal atrioventricular
      connection, which was more severe than that seen in Cx40(-/-)/Cx43(+/+) mice.
      Furthermore, muscular ventricular septal defects, premature closure of the ductus
      arteriosus, and subcutaneous edema were noticed in these embryos. Cx40(+/-)/Cx43(
      /-) embryos showed the same phenotype (ie, obstructed right ventricular outflow
      tract) as reported for Cx40(+/+)/Cx43(-/-) mice. These findings demonstrate that
      Cx43 haploinsufficiency aggravates the abnormalities observed in the Cx40(-/-)
      phenotype, whereas Cx40 haploinsufficiency does not worsen the Cx43(-/-)
      phenotype. We conclude that the gap-junctional proteins Cx40 and Cx43 contribute
      to morphogenesis of the heart in an isotype-specific manner.

PMID- 10969039
TI  - Increased nitric oxide synthase activity and expression in the human uterine
      artery during pregnancy.
AB  - Evidence exists that NO plays a role in the vasodilation that occurs during
      pregnancy. The purpose of the present study was to determine whether the role of
      NO is associated with an increase in the activity and protein expression of NO
      synthase (NOS) in the human uterine artery. Uterine arteries were obtained from
      pregnant patients (P arteries) and nonpregnant patients (NP arteries). NOS
      activity was estimated with the L-[(3)H]-arginine-to-L-[(3)H]-citrulline
      conversion method and on the basis of changes in tissue levels of cGMP. Western
      immunoblotting and immunohistochemistry were used to assess NOS protein
      expression. Ca(2+)-dependent NOS activity was 8 times greater (P:<0.01) in P than
      in NP arteries. Although most of this pregnancy-induced increase in NOS activity
      was Ca(2+) dependent (64%), a considerable portion was Ca(2+) independent.
      Expressions of endothelial NOS (eNOS) and neuronal NOS, but not inducible NOS,
      were demonstrated in P and NP arteries. The eNOS was located in the endothelium
      and stained with a qualitative order of P arteries>NP arteries (follicular)>NP
      arteries (luteal). The neuronal NOS was located in the adventitia of P and NP
      arteries. Basal NO-dependent and bradykinin-stimulated levels of cGMP were higher
      (P:<0.05) in P than in NP arteries. These results indicate that an upregulation
      of eNOS protein expression could account for the increased NO synthesis/release
      in the human uterine artery during pregnancy.

PMID- 10969040
TI  - Protein kinase C activation contributes to microvascular barrier dysfunction in
      the heart at early stages of diabetes.
AB  - The functional disturbance of microvasculature is recognized as an initiating
      mechanism that underlies the development of various diabetic complications.
      Although a causal relationship between microvascular leakage and tissue damage
      has been well documented in diabetic kidneys and eyes, there is a lack of
      information regarding the barrier function of coronary exchange vessels in the
      disease state. The aim of the present study was to evaluate the permeability
      property of coronary microvessels during the early development of experimental
      diabetes with a focus on the protein kinase C (PKC)-dependent signaling
      mechanism. The apparent permeability coefficient of albumin (Pa) was measured in
      isolated and perfused porcine coronary venules. The administration of high
      concentrations of D-glucose induced a dose-dependent increase in the Pa value,
      which was prevented by blockage of PKC with its selective inhibitors
      bisindolylmaleimide and Goe 6976. More importantly, an elevated basal
      permeability to albumin was observed in coronary venules at the early onset of
      streptozotocin-induced diabetes. The hyperpermeability was corrected with
      bisindolylmaleimide and the selective PKCbeta inhibitor hispidin. Concomitantly,
      protein kinase assay showed a high PKC activity in isolated diabetic venules.
      Immunoblot analysis of the diabetic heart revealed a significant subcellular
      translocation of PKCbetaII and PKCepsilon from the cytosol to the membrane,
      indicating that the specific activity of these isoforms was preferentially
      elevated. The results suggest that endothelial barrier dysfunction attributed to
      the activation of PKC occurs at the coronary exchange vessels in early diabetes.

PMID- 10969041
TI  - Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or
      doxycycline aggravates pulmonary hypertension in rats.
AB  - Chronic hypoxic pulmonary hypertension (PH) results from persistent
      vasoconstriction, excess muscularization, and extracellular matrix remodeling of
      pulmonary arteries. The matrix metalloproteinases (MMPs) are a family of
      proteinases implicated in extracellular matrix turnover and hence in smooth
      muscle and endothelial cell migration and proliferation. Because MMP expression
      and activity are increased in PH, we designed the present study to investigate
      whether inhibition of lung MMPs in rats subjected to chronic hypoxia (CH)
      contributes to or protects against vascular remodeling and PH. To achieve lung
      MMP inhibition, rats exposed to 10% O(2) for 15 days were treated with either
      doxycycline (20 mg/kg per day by gavage starting 2 days before and continuing
      throughout the CH period) or a single dose of recombinant adenovirus (Ad) for the
      human tissue inhibitors of metalloproteinases-1 (hTIMP-1) gene (Ad.hTIMP-1, 10(8)
      plaque-forming units given intratracheally 2 days before CH initiation). Control
      groups either received no treatment or were treated with an adenovirus containing
      no gene in the expression cassette (Ad.Null). Efficacy of hTIMP-1 gene transfer
      was assessed both by ELISA on bronchoalveolar lavages and by hTIMP-1
      immunofluorescence on lung sections. MMP inhibition in lungs was evaluated by in
      situ zymography and gelatinolytic activity assessment using [(3)H]gelatin. Rats
      treated with either doxycycline or Ad.hTIMP-1 had higher pulmonary artery
      pressure and right heart ventricular hypertrophy more severe than their
      respective controls. Worsening of PH was associated with increased
      muscularization and periadventitial collagen accumulation in distal arteries. In
      conclusion, our study provides compelling evidence that MMPs play a pivotal role
      in protecting against pulmonary artery remodeling.

PMID- 10969043
TI  - Preface.
AB  - Although the clinical presentation and the treatment of lower urinary tract
      infection (UTI) have changed little in the 60 to 70 years of the 'antibiotic
      era', uropathogenic bacteria have not been slow to respond to the selecting
      pressure of antimicrobials. This is because such infections are common.
      Approximately 3% of all consultations made to general practitioners are for
      symptoms of UTI and approximately 12-20% of all antibiotic prescriptions are for
      this indication. Between one-quarter and one-half of all women experience a UTI
      at some time. The problem, therefore, is a considerable one and warrants
      reevaluation. This supplement is based upon papers presented at a meeting held in
      March 2000 in Vienna, Austria and sponsored by Leo Pharmaceutical Laboratories.
      It draws together the current views on the diagnosis and the treatment of UTIs at
      a time when the disease-causing microorganisms are most certainly changing.
      Antibiotic resistance to commonly used agents, such as trimethoprim and
      ampicillin, often now exceeds 30-50%. The clinician may be tempted to choose an
      agent such as a fluoroquinolone for the treatment of this disease, yet it is
      known that fluoroquinolone resistance can develop rapidly. Views on the length of
      treatment have also changed over the years and a 3 day regimen is usually now
      advocated. Pivmecillinam, which is hydrolysed to mecillinam after absorption, has
      a novel mode of action, rapid bacterial cell penetration and lower affinity for
      common beta-lactamases. Its spectrum of activity and good safety profile make it
      an ideal candidate for the treatment of this common condition. Experience in
      several countries over many years confirms this assessment and it may be time to
      reconsider the potential role of pivmecillinam in the treatment of UTIs. The
      Editors would like to thank Inge Boe and Paul Menday of Leo Laboratories for
      their untiring support and assistance in the preparation of this supplement.

PMID- 10969042
TI  - A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts
      angiotensin I to angiotensin 1-9.
AB  - ACE2, the first known human homologue of angiotensin-converting enzyme (ACE), was
      identified from 5' sequencing of a human heart failure ventricle cDNA library.
      ACE2 has an apparent signal peptide, a single metalloprotease active site, and a
      transmembrane domain. The metalloprotease catalytic domains of ACE2 and ACE are
      42% identical, and comparison of the genomic structures indicates that the two
      genes arose through duplication. In contrast to the more ubiquitous ACE, ACE2
      transcripts are found only in heart, kidney, and testis of 23 human tissues
      examined. Immunohistochemistry shows ACE2 protein predominantly in the
      endothelium of coronary and intrarenal vessels and in renal tubular epithelium.
      Active ACE2 enzyme is secreted from transfected cells by cleavage N-terminal to
      the transmembrane domain. Recombinant ACE2 hydrolyzes the carboxy terminal
      leucine from angiotensin I to generate angiotensin 1-9, which is converted to
      smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture.
      ACE2 can also cleave des-Arg bradykinin and neurotensin but not bradykinin or 15
      other vasoactive and hormonal peptides tested. ACE2 is not inhibited by
      lisinopril or captopril. The organ- and cell-specific expression of ACE2 and its
      unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in
      the local renin-angiotensin system of the heart and kidney. The full text of this
      article is available at http://www. circresaha.org.

PMID- 10969044
TI  - Pathogenesis of urinary tract infections: an update.
AB  - The pathogenesis of uncomplicated urinary tract infection (UTI) is complex and
      influenced by many host biological and behavioural factors and by properties of
      the infecting uropathogens. Most uncomplicated UTIs in women are not associated
      with underlying functional or anatomical abnormalities of the urinary tract,
      whereas sexual intercourse, spermicide use, a history of recurrent UTI and recent
      antimicrobial chemotherapy are important risk factors. A maternal history of UTI
      and young age at first UTI, as well as sexual intercourse and spermicide use, are
      risk factors for recurrent UTI in young women. In some young healthy women,
      especially those with 'low UTI risk' behaviour, features of pelvic anatomy appear
      to be associated with UTI risk. In postmenopausal women, anatomical and
      functional characteristics of the genitourinary tract are more strongly
      associated with UTI risk than in younger women. A genetic predisposition to
      recurrent UTI is suggested by the association of recurrent UTI in certain age
      groups with the ABH blood group non-secretor phenotype, a maternal history of UTI
      and early age at onset of UTI. Virulence determinants of uropathogens are much
      more important in the normal host than in the host who has a functional or
      anatomical abnormality of the genitourinary tract.

PMID- 10969045
TI  - Preface.
AB  - Although the clinical presentation and the treatment of lower urinary tract
      infection (UTI) have changed little in the 60 to 70 years of the 'antibiotic
      era', uropathogenic bacteria have not been slow to respond to the selecting
      pressure of antimicrobials. This is because such infections are common.
      Approximately 3% of all consultations made to general practitioners are for
      symptoms of UTI and approximately 12-20% of all antibiotic prescriptions are for
      this indication. Between one-quarter and one-half of all women experience a UTI
      at some time. The problem, therefore, is a considerable one and warrants
      reevaluation. This supplement is based upon papers presented at a meeting held in
      March 2000 in Vienna, Austria and sponsored by Leo Pharmaceutical Laboratories.
      It draws together the current views on the diagnosis and the treatment of UTIs at
      a time when the disease-causing microorganisms are most certainly changing.
      Antibiotic resistance to commonly used agents, such as trimethoprim and
      ampicillin, often now exceeds 30-50%. The clinician may be tempted to choose an
      agent such as a fluoroquinolone for the treatment of this disease, yet it is
      known that fluoroquinolone resistance can develop rapidly. Views on the length of
      treatment have also changed over the years and a 3 day regimen is usually now
      advocated. Pivmecillinam, which is hydrolysed to mecillinam after absorption, has
      a novel mode of action, rapid bacterial cell penetration and lower affinity for
      common beta-lactamases. Its spectrum of activity and good safety profile make it
      an ideal candidate for the treatment of this common condition. Experience in
      several countries over many years confirms this assessment and it may be time to
      reconsider the potential role of pivmecillinam in the treatment of UTIs. The
      Editors would like to thank Inge Boe and Paul Menday of Leo Laboratories for
      their untiring support and assistance in the preparation of this supplement.

PMID- 10969046
TI  - Comparative potency of mecillinam and other beta-lactam antibiotics against
      Escherichia coli strains producing different beta-lactamases.
AB  - The activity of mecillinam, a beta-lactam antibiotic with high affinity for Gram
      negative penicillin-binding protein 2 (PBP2), was assessed against ampicillin
      resistant Escherichia coli strains producing beta-lactamases representing the
      three molecular classes, A (TEM-1 and -3, SHV-3 and IRT-5), C (AmpC) and D (OXA
      3). The antimicrobial activity of mecillinam and other beta-lactam antibiotics
      was evaluated by determining their MICs on Mueller-Hinton agar. The time course
      of hydrolysis in crude extracts prepared from the various beta-lactamase
      producing strains was also measured and was used to determine the relative rate
      of hydrolysis and the apparent affinity for ampicillin, cephalothin and
      mecillinam. When compared with the other beta-lactam antibiotics, mecillinam
      demonstrated significantly greater antibacterial potency and higher stability to
      beta-lactamase hydrolysis in TEM-, IRT- and AmpC-producing isolates. These
      findings confirm that the antimicrobial potency of mecillinam compares favourably
      with those of the other penicillins included in the present study, suggesting
      that mecillinam use in the treatment of infections caused by Gram-negative
      bacteria should be re-evaluated.

PMID- 10969047
TI  - The ECO*SENS Project: a prospective, multinational, multicentre epidemiological
      survey of the prevalence and antimicrobial susceptibility of urinary tract
      pathogens-interim report.
AB  - The ECO*SENS Project is the first international survey to investigate the
      prevalence and susceptibility of pathogens causing community-acquired,
      uncomplicated urinary tract infections (UTIs) in women. At 240 centres in 17
      countries, female patients presenting with symptoms of uncomplicated UTIs were
      asked to provide a urine sample for testing for the presence of leucocytes and
      bacteria. The bacteria were identified and their susceptibility to 12 antibiotics
      commonly used in the treatment of UTIs was determined. The objective of the
      survey was to collect 5000 urine samples to obtain approximately 3500 isolates of
      defined uropathogens. This interim report includes the results from 1960 urine
      samples, 75% of which contained a uropathogen. Escherichia coli accounted for the
      majority (80%) of uropathogens isolated in all 17 countries. The rates of
      resistance among E. coli strains were: ampicillin and sulphamethoxazole, 30%;
      trimethoprim alone or with sulphamethoxazole, 15%; nalidixic acid, 6%;
      ciprofloxacin, 3%; amoxycillin-clavulanic acid, mecillinam, cefadroxil,
      nitrofurantoin and fosfomycin, 2%. The use of ampicillin, sulphonamides and
      trimethoprim alone or with sulphamethoxazole needs to be reconsidered. The
      seemingly rapid increase in quinolone resistance among community-acquired E. coli
      in some of the countries gives cause for concern.

PMID- 10969048
TI  - Treatment options for acute uncomplicated cystitis in adults.
AB  - Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a
      patient with a structurally and functionally normal urinary tract. Acute
      uncomplicated cystitis is observed chiefly in women. It needs, however, to be
      differentiated depending on whether it occurs in premenopausal, postmenopausal or
      pregnant women. Only a small number of 15-50 year old, otherwise healthy men
      suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single
      dose antimicrobial therapy is generally less effective than the same antibiotic
      used for longer duration. However, most antimicrobial agents given for 3 days are
      as effective as those given for longer duration, and adverse events tend to be
      found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be
      recommended as first-line empirical therapy only in communities with resistance
      rates of uropathogens to trimethoprim of </=10-20%. Otherwise fluoroquinolones
      are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as
      second- or third-generation oral cephalosprins or pivmecillinam, especially when
      fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia
      coli strains in the community are already resistant to fluoroquinolones, as in
      Spain, for example. Recurrent UTIs are common among young, healthy women even
      though they generally have anatomically and physiologically normal urinary
      tracts. The following prophylactic antimicrobial regimens are recommended: (i)
      the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii)
      post-coital prophylaxis for women in whom episodes of infection are associated
      with sexual intercourse. Other prophylactic methods are not as yet as effective
      as antimicrobial prophylaxis.

PMID- 10969049
TI  - Which antibiotics are appropriate for treating bacteriuria in pregnancy?
AB  - Bacteriuria in pregnancy, with or without clinical symptoms, is frequent. If left
      untreated, it can in 20-30% of cases lead to acute pyelonephritis, which is a
      serious threat to the mother and fetus, increasing the risk of preterm labour and
      low birthweight infants. This paper is a review of the literature concerning
      antibacterial treatment of bacteriuria in pregnancy. It is crucial to ensure that
      drugs to be used in pregnancy are safe and effective. Established first-line
      drugs such as ampicillin (pivampicillin) and amoxycillin, and other commonly used
      treatments such as trimethoprim-sulphamethoxazole, are associated with a high
      degree of resistance in Escherichia coli, the most common pathogen in the urinary
      tract. A recent survey of physicians in Denmark, Finland, Norway and Sweden
      confirms that beta-lactam antibiotics (particularly pivmecillinam) and
      nitrofurantoin are the drugs of first choice in the treatment of bacteriuria in
      pregnancy in the Nordic countries. No teratogenic effects have been associated
      with these agents. In contrast to nitrofurantoin, pivmecillinam is also efficient
      against pyelonephritis. In spite of resistance in E. coli and possible adverse
      effects on the fetus, many physicians still prescribe sulphonamides during the
      first two trimesters of pregnancy.

PMID- 10969050
TI  - Pivmecillinam in the treatment of urinary tract infections.
AB  - The efficacy of pivmecillinam for empirical treatment of acute uncomplicated
      urinary tract infection (UTI) was initially reported in clinical trials published
      in the 1970s and 1980s. Bacteriological cure rates observed in these trials were
      consistently >85%, and studies of different dosing regimens suggested that a 3
      day course was appropriate. Comparative studies reported that pivmecillinam was
      equivalent to other antimicrobial agents in terms of clinical and bacteriological
      outcomes. These studies also documented that pivmecillinam was effective for
      treatment of Staphylococcus saprophyticus infections, was acceptable for use in
      pregnancy and was well tolerated. Subsequent widespread use of pivmecillinam in
      Scandinavian countries has led to a body of clinical experience which confirms
      the efficacy and safety of this antimicrobial agent in the treatment of acute
      cystitis. Recently, two large, prospective, randomized, double-blind, multi
      centre clinical trials have been completed to assist in defining the role of this
      antimicrobial agent in the treatment of acute cystitis. A comparison of 3 day
      courses of pivmecillinam or norfloxacin, both at 400 mg bd, showed higher
      bacteriological cure rates with norfloxacin but generally similar clinical
      outcomes. A second, dose-ranging study found that pivmecillinam, given bd for 7
      days, led to superior bacteriological and clinical outcomes at short-term follow
      up than the 3 day regimen. Pooling bacteriological outcomes from the two studies
      showed similar outcomes with 7 days of pivmecillinam 200 mg bd or 3 days of
      norfloxacin 400 mg bd. The shorter, 3 day, course achieved similar short-term
      clinical outcomes to 7 days of pivmecillinam and 3 days of norfloxacin in women
      aged </=50 years. These recent studies confirm earlier reports and clinical
      experience that pivmecillinam is effective and well tolerated for the treatment
      of acute cystitis in women.

PMID- 10969051
TI  - Effect on the human normal microflora of oral antibiotics for treatment of
      urinary tract infections.
AB  - Oral administration of antibiotics for treatment of urinary tract infections
      (UTIs) can cause ecological disturbances in the normal intestinal microflora.
      Poorly absorbed drugs can reach the colon in active form, suppress susceptible
      microorganisms and disturb the ecological balance. Suppression of the normal
      microflora may lead to reduced colonization resistance with subsequent overgrowth
      of pre-existing, naturally resistant microorganisms, such as yeasts and
      Clostridium difficile. New colonization by resistant potential pathogens may also
      occur and may spread within the body or to other patients and cause severe
      infections. It is therefore important to learn more about the ecological effects
      of antibacterial agents on the human microflora. The impact on intestinal
      microorganisms of oral antibiotics used for the treatment of UTIs is reviewed
      here. Ampicillin, amoxycillin and co-amoxiclav suppress both the aerobic and
      anaerobic intestinal microflora with overgrowth of ampicillin-resistant
      Enterobacteriaceae. Pivmecillinam also affects the intestinal microflora,
      suppressing Escherichia coli, but does not have a major effect on the anaerobic
      microflora. Several orally administered cephalosporins, such as cefixime,
      cefpodoxime, cefprozil and ceftibuten, reduce the number of Enterobacteriaceae
      and increase the number of enterococci. Colonization with C. difficile has also
      been observed. Fluoroquinolones eliminate or strongly suppress intestinal
      Enterobacteriaceae, but affect enterococci and anaerobic bacteria only slightly.
      When antimicrobial agents are prescribed for the treatment of UTIs, not only the
      antimicrobial spectrum of the agent but also the potential ecological
      disturbances, including the risk of emergence of resistant strains, should be
      considered.

PMID- 10969052
TI  - Survey on antibiotic usage in the treatment of urinary tract infections.
AB  - Ninety-two clinical microbiologists, infectious disease clinicians and clinicians
      with an interest in the management of urinary tract infections (UTIs)
      participated in an interactive session concerning the management of acute
      uncomplicated lower UTI. The antibacterials considered most appropriate as first
      line agents were trimethoprim, co-trimoxazole, pivmecillinam, nitrofurantoin and
      fluoroquinolones. The current level of usage of fluoroquinolones for lower UTIs
      was, however, considered inappropriate by most delegates from a 'societal
      perspective', in terms of spread of resistance and potential impact on the
      environment.

PMID- 10969053
TI  - Environmental risk assessment of antibiotics: comparison of mecillinam,
      trimethoprim and ciprofloxacin.
AB  - The effects of mecillinam, trimethoprim and ciprofloxacin, antibiotics used in
      the treatment of urinary tract infections, on the aquatic environment were
      assessed. Mecillinam and ciprofloxacin were both readily biodegradable (primary
      degradation) in activated sludge, whereas trimethoprim persisted. The toxicity of
      these antibiotics towards sludge bacteria, a green alga, a cyanobacterium, a
      crustacean and a fish were investigated; both mecillinam and ciprofloxacin were
      highly toxic to the cyanobacterium Microcystis aeruginosa (EC(50) in the range 5
      60 Ig/L). Risk characterization for the aquatic environment was performed for the
      three compounds by calculating the predicted environmental concentration (PEC)
      and the predicted no-effects concentration (PNEC). A PEC/PNEC ratio of <1
      indicates that, with the present pattern of use, no environmental risk is
      expected. PEC/PNEC ratios of <1 for present usage in Europe were found for
      mecillinam and trimethoprim whereas a PEC/PNEC ratio >1 was found for
      ciprofloxacin.

PMID- 10969054
TI  - Ecological antibiotic policy.
AB  - Development of resistance to antibiotics is a major problem worldwide. The normal
      oropharyngeal flora, the intestinal flora and the skin flora play important roles
      in this development. Within a few days after the onset of antibiotic therapy,
      resistant Escherichia coli, Haemophilus influenzae and Staphylococcus epidermidis
      can be detected in the normal flora of volunteers or patients. Horizontal spread
      of the resistance genes to other species, e.g. SALMONELLA: spp., Staphylococcus
      aureus and Streptococcus pneumoniae, occurs by conjugation or transformation. An
      ecologically sound antibiotic policy favours the use of antibiotics with little
      or no impact on the normal flora. Prodrug antibiotics which are not active
      against the bacteria in the mouth and the intestine (before absorption) and which
      are not excreted to a significant degree via the intestine, saliva or skin are
      therefore preferred. Prodrugs such as pivampicillin, bacampicillin, pivmecillinam
      and cefuroxime axetil are favourable from an ecological point of view. Experience
      from Scandinavia supports this, since resistance to mecillinam after 20 years of
      use is low (about 5%) and stable.

PMID- 10969055
TI  - Progress in the management of urinary tract infections: discussion.

PMID- 10969056
TI  - Preface.
AB  - Although the clinical presentation and the treatment of lower urinary tract
      infection (UTI) have changed little in the 60 to 70 years of the 'antibiotic
      era', uropathogenic bacteria have not been slow to respond to the selecting
      pressure of antimicrobials. This is because such infections are common.
      Approximately 3% of all consultations made to general practitioners are for
      symptoms of UTI and approximately 12-20% of all antibiotic prescriptions are for
      this indication. Between one-quarter and one-half of all women experience a UTI
      at some time. The problem, therefore, is a considerable one and warrants
      reevaluation. This supplement is based upon papers presented at a meeting held in
      March 2000 in Vienna, Austria and sponsored by Leo Pharmaceutical Laboratories.
      It draws together the current views on the diagnosis and the treatment of UTIs at
      a time when the disease-causing microorganisms are most certainly changing.
      Antibiotic resistance to commonly used agents, such as trimethoprim and
      ampicillin, often now exceeds 30-50%. The clinician may be tempted to choose an
      agent such as a fluoroquinolone for the treatment of this disease, yet it is
      known that fluoroquinolone resistance can develop rapidly. Views on the length of
      treatment have also changed over the years and a 3 day regimen is usually now
      advocated. Pivmecillinam, which is hydrolysed to mecillinam after absorption, has
      a novel mode of action, rapid bacterial cell penetration and lower affinity for
      common beta-lactamases. Its spectrum of activity and good safety profile make it
      an ideal candidate for the treatment of this common condition. Experience in
      several countries over many years confirms this assessment and it may be time to
      reconsider the potential role of pivmecillinam in the treatment of UTIs. The
      Editors would like to thank Inge Boe and Paul Menday of Leo Laboratories for
      their untiring support and assistance in the preparation of this supplement.

PMID- 10969058
TI  - Preface.

PMID- 10969059
TI  - MYSTIC (Meropenem Yearly Susceptibility Test Information Collection): a global
      overview.
AB  - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) is a
      global, multicentre surveillance study that compares the activity of meropenem in
      centres that are prescribers with that of imipenem, ceftazidime,
      piperacillin/tazobactam, ciprofloxacin and gentamicin. Of the 46 centres
      (intensive care units, cystic fibrosis units, neutropenia units and general
      wards) contributing to this study, 29 were in Europe, 14 in the Americas and
      three in the Middle East and Asia. The results for the most common isolates
      obtained in the first year of the study from these three regions show that
      meropenem has a broad spectrum of activity and potency in these centres, with 89%
      of the 6890 strains tested having an MIC 4 mg/L. The overall susceptibility was
      lower for the comparator antibiotics. There was evidence in all regions of
      strains producing beta-lactamases and other resistance mechanisms against the
      other beta-lactams tested, fluoroquinolones and aminoglycosides. Future years'
      results from this surveillance study will show whether meropenem will continue to
      exhibit such activity.

PMID- 10969057
TI  - Detection of emerging resistance patterns within longitudinal surveillance
      systems: data sensitivity and microbial susceptibility.
AB  - Communicating information from antimicrobial resistance surveillance study data
      to microbiologists and physicians can be challenging. Large amounts of data,
      commonly reaching millions of MICs or zone 20diameter endpoints, must be analysed
      and condensed to easily-read tables or figures. Furthermore, data must not be
      prejudged relative to susceptibility categories, because of the diverse nature of
      interpretive criteria available internationally. An attempt must be made to
      present results of all surveillance studies in a mode that can be reinterpreted
      for immediate use in different geographical areas, or used to compare future data
      with relative ease and high accuracy. Such data displays require peer-reviewed
      journals to permit greater numbers of more complex tables to present results. The
      Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) study is a
      year-on-year global surveillance programme in medical centres where meropenem is
      available for use. We have developed a presentation strategy that expands the
      long-term clinical value of MYSTIC results. In addition to statistical
      parameters, tables of cumulative percentages or numbers of strains inhibited at
      each tested antimicrobial concentration will be presented. Alternative figures
      (Finland-o-grams) could also be used, but these generally lack precise
      extractable rates and require more journal space. Regardless of study design,
      promotion of this presentation philosophy enhances any surveillance study's value
      to each reader or user and facilitates application to locally appropriate
      interpretations. The widespread use of these analysis and presentation principles
      as benchmarks by various resistance studies and networks is strongly encouraged,
      particularly by investigations across international boundaries.

PMID- 10969060
TI  - MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from
      the Americas: resistance implications in the treatment of serious infections.
AB  - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC)
      programme aims to provide in vitro surveillance data for geographically diverse
      institutions where meropenem is available for use. The in vitro activity of
      meropenem and eight comparator antimicrobial agents against 2340 significant
      pathogens obtained in 1999 was assessed and compared in 14 study centres in
      Brazil, Mexico and the USA. Isolates were further characterized for production of
      extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and
      carbapenemases. Carbapenems demonstrated their broad spectrum and potency,
      inhibiting >/=95% of all isolates irrespective of the geographical region or
      centre type. The overall order of activity of the nine agents tested against all
      pathogens in 1999 was meropenem (96%) > imipenem (95%) > cefepime (92%) >
      gentamicin (89%) > piperacillin/tazobactam (88%) > ceftazidime = tobramycin (86%)
      > cefotaxime (84%) > ciprofloxacin (83%). Thus far, the results from the Americas
      indicate that meropenem has excellent potency and spectrum of activity despite
      being prescribed for the treatment of seriously ill patients. In contrast, other
      ESBLs, fluoroquinolones and aminoglycosides have lost activity in many
      institutions as a result of the selection of strains producing ESBLs or having
      AmpC and other resistance determinants. Carbapenem resistance was observed rarely
      and at a prevalence similar to those reported in earlier studies. Carbapenems
      appear to be a continuing reliable option for the treatment of serious nosocomial
      infection.

PMID- 10969061
TI  - MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from
      Europe: comparison of antibiotic susceptibilities between countries and centre
      types.
AB  - The activity of meropenem and five comparators has been studied against 7886
      isolates from 29 centres in 10 European countries from 1997 to 1999 as part of
      the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC)
      surveillance study. Gram-positive and Gram-negative isolates from intensive care
      units (ICUs), neutropenia centres, cystic fibrosis (CF) centres and general wards
      were investigated in Belgium (1 year), Czech Republic (2 years), Germany (3
      years), Italy (3 years), Poland (2 years), Russia (2 years), Sweden (2 years),
      Switzerland (1 year), Turkey (1 year) and UK (3 years). Resistance to quinolones
      and aminoglycosides was observed, as was resistance to the cephalosporins and
      penicillins via extended-spectrum beta-lactamases (ESBLs) and AmpC beta
      lactamases. Meropenem showed good activity against the pathogens tested,
      particularly in CF and neutropenia centres, over the 3 year period. The overall
      order of potency of the six antimicrobial agents tested was: meropenem > imipenem
      > piperacillin/tazobactam and ciprofloxacin > ceftazidime > gentamicin. No
      increase in resistance to the carbapenems, to date, has been detected in any of
      the European centres included in this study.

PMID- 10969062
TI  - Surveillance studies: how can they help the management of infection?
AB  - The increase in antimicrobial resistance has led to predictions of doom in the
      international press and to depression in the medical community. It has focused
      attention upon measures for fighting resistance, foremost of which is
      susceptibility surveillance. Until recently, global efforts at surveillance have
      been largely uncoordinated and random. This scene is rapidly changing with the
      World Health Organization (WHO), among others, leading multidisciplinary,
      targeted initiatives. In terms of individual surveillance programmes, much has
      been learned about their design. The best of these, the Meropenem Yearly
      Susceptibility Test Information Collection (MYSTIC), SENTRY and the Alexander
      Project, involve well-defined patient and organism groups against key
      denominators, and use standardized, internationally recognized methods that are
      quality-controlled, explore susceptibility quantitatively and include
      investigation of resistance mechanisms. Results are rapidly returned to the user.
      Evidence shows that surveillance, when used to guide policies on antibiotic use
      and infection control, can be helpful in the fight to control the development and
      spread of resistance. Further work is required to demonstrate these benefits and
      quantify them fully.

PMID- 10969063
TI  - Preface.
AB  - Efficient monitoring for the emergence of resistance to various antimicrobial
      agents has, in the face of global trends in resistance, recently assumed great
      importance. Many programmes have been developed to survey resistance, each
      varying in scope or emphasis as well as commitment to long-term monitoring. A
      programme that specifically addresses pathogens from populations of the most
      severely ill patients is the Meropenem Yearly Susceptibility Test Information
      Collection (MYSTIC). This programme was started in 1997 to monitor carbapenem
      activity in vitro in centres using carbapenems because their prevalent strains
      were resistant to other beta-lactams and drug classes. Meropenem is a broad
      spectrum carbapenem and differs microbiologically from imipenem by having a
      greater potency in vitro against many Gram-negative pathogens and a slightly
      lower potency against some Gram-positive pathogens. Meropenem has improved
      stability to renal-based enzymatic metabolism, and does not require the addition
      of an enzyme inhibitor such as cilastatin. Material in this publication is based
      on the many abstracts and oral presentations delivered at recent national and
      international meetings including: the International Congress of Infectious
      Disease in Buenos Aires, Argentina (April, 2000); the European Congress of
      Chemotherapy in Madrid, Spain (May, 2000); and the European Congress of Clinical
      Microbiology and Infectious Disease in Stockholm, Sweden (May, 2000). All of the
      authors are active participants in the MYSTIC programme and bring to it
      experience in the design of surveillance studies and the detection of resistance
      mechanisms. Professor Jones discusses the most useful ways of storing and
      presenting susceptibility data to preserve the long-term value of all results. He
      argues for the publication of expanded study details and the limited use of
      MIC(90) values or susceptibility rates. Dr Turner has coordinated the MYSTIC
      programme, and he summarizes here the similarities and differences in the results
      seen to date between the Americas, Europe and centres in Asia and the Middle
      East. The Americas have been one of the most recently monitored regions.
      Professors Pfaller and Jones give baseline data for the USA (10 sites), Mexico
      and Brazil. Professor Goossen's article focuses on the results of MYSTIC in the
      European centres. Doctor Masterton presents a comprehensive overview of various
      surveillance studies and assesses their value and characteristics for the
      continued optimal management of infected patients.

PMID- 10969064
TI  - Stabilization of the GDP-bound conformation of Gialpha by a peptide derived from
      the G-protein regulatory motif of AGS3.
AB  - The G-protein regulatory (GPR) motif in AGS3 was recently identified as a region
      for protein binding to heterotrimeric G-protein alpha subunits. To define the
      properties of this approximately 20-amino acid motif, we designed a GPR consensus
      peptide and determined its influence on the activation state of G-protein and
      receptor coupling to G-protein. The GPR peptide sequence (28 amino acids)
      encompassed the consensus sequence defined by the four GPR motifs conserved in
      the family of AGS3 proteins. The GPR consensus peptide effectively prevented the
      binding of AGS3 to Gialpha1,2 in protein interaction assays, inhibited guanosine
      5'-O-(3-thiotriphosphate) binding to Gialpha, and stabilized the GDP-bound
      conformation of Gialpha. The GPR peptide had little effect on nucleotide binding
      to Goalpha and brain G-protein indicating selective regulation of Gialpha. Thus,
      the GPR peptide functions as a guanine nucleotide dissociation inhibitor for
      Gialpha. The GPR consensus peptide also blocked receptor coupling to
      Gialphabetagamma indicating that although the AGS3-GPR peptide stabilized the GDP
      bound conformation of Gialpha, this conformation of Gialpha(GDP) was not
      recognized by a G-protein coupled receptor. The AGS3-GPR motif presents an
      opportunity for selective control of Gialpha- and Gbetagamma-regulated effector
      systems, and the GPR motif allows for alternative modes of signal input to G
      protein signaling systems.

PMID- 10969065
TI  - Clastogenic effect of the human T-cell leukemia virus type I Tax oncoprotein
      correlates with unstabilized DNA breaks.
AB  - Expression of the human T-cell leukemia virus type I (HTLV-I) Tax oncoprotein
      rapidly engenders DNA damage as reflected in a significant increase of
      micronuclei (MN) in cells. To understand better this phenomenon, we have
      investigated the DNA content of MN induced by Tax. Using an approach that we
      termed FISHI, fluorescent in situ hybridization and incorporation, we attempted
      to characterize MN with centric or acentric DNA fragments for the presence or
      absence of free 3'-OH ends. Free 3'-OH ends were defined as those ends accessible
      to in situ addition of digoxigenin-dUTP using terminal deoxynucleotidyl
      transferase. MN were also assessed for centromeric sequences using standard
      fluorescent in situ hybridization (FISH). Combining these results, we determined
      that Tax oncoprotein increased the frequency of MN containing centric DNA with
      free 3'-OH and decreased the frequency of MN containing DNA fragments that had
      incorporation-inaccessible 3'-ends. Recently, it has been suggested that
      intracellular DNA breaks without detectable 3'-OH ends are stabilized by the
      protective addition of telomeric caps, while breaks with freely detectable 3'-OH
      are uncapped and are labile to degradation, incomplete replication, and loss
      during cell division. Accordingly, based on increased detection of free 3'-OH
      containing DNA fragments, we concluded that HTLV-I Tax interferes with protective
      cellular mechanism(s) used normally for stabilizing DNA breaks.

PMID- 10969066
TI  - Suppression of intestinal polyposis in Apc(delta 716) knockout mice by an
      additional mutation in the cytosolic phospholipase A(2) gene.
AB  - Arachidonic acid is a precursor for biosynthesis of eicosanoids, including
      prostaglandins, thromboxanes, leukotrienes, and lipoxins. Cytosolic phospholipase
      A(2) (cPLA(2)) plays a key role in the release of arachidonic acid as the
      substrate of cyclooxygenase-1 (COX-1) or COX-2. We found that the level of
      cPLA(2) mRNA was markedly elevated in the polyps and correlated with the polyp
      size in the small intestine of the Apc(delta)(716) knockout mouse, a model for
      human familial adenomatous polyposis. To determine the role of cPLA(2) in
      intestinal tumorigenesis, we then introduced a cPLA(2) gene mutation into
      Apc(delta)(716) mice. In the compound mutant mice, the size of the small
      intestinal polyps was reduced significantly, although the numbers remained
      unchanged. These results provide direct genetic evidence that cPLA(2) plays a key
      role in the expansion of polyps in the small intestine rather than in the
      initiation process. In contrast, colonic polyps were not affected in either size
      or number. Interestingly, group X sPLA(2) was constitutively expressed in the
      colon at much higher levels than in the small intestine. These results suggest
      that in the colon, group X sPLA(2) supplies arachidonic acid in both the normal
      epithelium and the polyps even in the absence of cPLA(2).

PMID- 10969067
TI  - The neuropeptide processing enzyme EC 3.4.24.15 is modulated by protein kinase A
      phosphorylation.
AB  - The metalloendopeptidase EC (EP24.15) is a neuropeptide-metabolizing enzyme
      expressed predominantly in brain, pituitary, and testis, and is implicated in
      several physiological processes and diseases. Multiple putative phosphorylation
      sites in the primary sequence led us to investigate whether phosphorylation
      effects the specificity and/or the kinetics of substrate cleavage. Only protein
      kinase A (PKA) treatment resulted in serine phosphorylation with a stoichiometry
      of 1.11 +/- 0.12 mol of phosphate/mol of recombinant rat EP24.15. Mutation
      analysis of each putative PKA site, in vitro phosphorylation, and phosphopeptide
      mapping indicated serine 644 as the phosphorylation site. Phosphorylation effects
      on catalytic activity were assessed using physiological (GnRH, GnRH(1-9),
      bradykinin, and neurotensin) and fluorimetric (MCA-PLGPDL-Dnp and
      orthoaminobenzoyl-GGFLRRV-Dnp-edn) substrates. The most dramatic change upon PKA
      phosphorylation was a substrate-specific, 7-fold increase in both K(m) and k(cat)
      for GnRH. In both rat PC12 and mouse AtT-20 cells, EP24.15 was serine
      phosphorylated, and EP24.15 phosphate incorporation was enhanced by forskolin
      treatment, and attenuated by H89, consistent with PKA-mediated phosphorylation.
      Cloning of the full-length mouse EP24.15 cDNA revealed 96.7% amino acid identity
      to the rat sequence, and conservation at serine 644, consistent with its putative
      functional role. Therefore, PKA phosphorylation is suggested to play a regulatory
      role in EP24.15 enzyme activity.

PMID- 10969068
TI  - The immunologically protective P-4 antigen of Leishmania amastigotes. A
      developmentally regulated single strand-specific nuclease associated with the
      endoplasmic reticulum.
AB  - The purified membrane-associated Leishmania pifanoi amastigote protein P-4 has
      been shown to induce protective immunity against infection and to elicit
      preferentially a T helper 1-like response in peripheral blood mononuclear cells
      of patients with American cutaneous leishmaniasis. As this molecule is
      potentially important for future vaccine studies, the L. pifanoi gene encoding
      the P-4 membrane protein was cloned and sequenced. Southern blot analyses
      indicate the presence of six tandemly arrayed copies of the P-4 gene in L.
      pifanoi; homologues of the P-4 gene are found in all other species of the genus
      Leishmania examined. DNA-derived protein sequence data indicated an identity to
      the P1 zinc-dependent nuclease of Penicillium citrinum (20.8%) and the C-terminal
      domain of the 3' nucleotidase of Leishmania donovani (33.7%). Consistent with
      these sequence analyses, purified L. pifanoi P-4 protein possesses single strand
      nuclease (DNA and RNA) and phosphomonoesterase activity, with a preference for
      UMP > TMP > AMP >> CMP. Double-labeling immunofluorescence microscopic analyses
      employing anti-binding protein antibodies revealed that the P-4 protein is
      localized in the endoplasmic reticulum of the amastigote. Northern blot analyses
      indicated that the gene is selectively expressed in the intracellular amastigote
      stage (mammalian host) but not in the promastigote stage (insect) of the
      parasite. Based upon its subcellular localization and single-stranded specific
      nuclease activity, possible roles of the P-4 nuclease in the amastigote in RNA
      stability (gene expression) or DNA repair are discussed.

PMID- 10969069
TI  - Basic fibroblast growth factor utilizes both types of component subunits of Gs
      for dual signaling in human adipocytes. Stimulation of adenylyl cyclase via
      Galph(s) and inhibition of NADPH oxidase by Gbeta gamma(s).
AB  - Basic fibroblast growth factor (bFGF), a ligand of receptor protein-tyrosine
      kinases, promoted the dissociation of G(s) and had antagonistic stimulatory and
      inhibitory effects on adenylyl cyclase and NADPH oxidase in human fat cell plasma
      membranes. The bFGF-induced activation of adenylyl cyclase was blocked by COOH
      terminal anti-Galpha(s), indicating that it was mediated by Galpha(s). The
      inhibitory action of bFGF was mimicked by exogenously supplied Gbetagamma
      subunits and was reversed by anti-Gbeta(1/2), or betaARK-CT, a COOH-terminal beta
      adrenergic receptor kinase fragment that specifically binds free Gbetagamma,
      indicating that it was transduced by Gbetagamma complexes. The bFGF-induced
      inhibition of NADPH-dependent H(2)O(2) generation was also reversed by peptide
      100-119, an inhibitor of G(s) activation by ligand-occupied beta-adrenergic
      receptors, indicating that the Gbetagamma complexes mediating the inhibitory
      action of the growth factor are derived from G(s). The findings suggest a direct,
      non-kinase-dependent, coupling of bFGF receptor(s) to G(s) and provide the first
      example of a ligand of receptor protein-tyrosine kinases that is capable of
      utilizing both types of component subunits of a single heterotrimeric G protein
      for dual signaling in a single cell type.

PMID- 10969070
TI  - Generation and characterization of a recombinant human CCR5-specific antibody. A
      phage display approach for rabbit antibody humanization.
AB  - We describe the isolation of a CCR5-specific antibody, ST6, from an antibody
      phage display library generated from an immune rabbit. ST6 was previously shown
      to efficiently prevent the surface expression of CCR5 when expressed
      intracellularly (Steinberger, P., Andris-Widhopf, J., Buhler, B., Torbett, B. E.,
      and Barbas, C. F., III (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 805-810).
      Because ST6 has therapeutic potential in human immunodeficiency virus, type 1
      disease, its humanization was desired to minimize the potential for
      immunogenicity. ST6 was humanized using a phage display-based approach. Like the
      parental rabbit clone, the humanized version ST6/34 efficiently prevented the
      surface expression of CCR5. The conserved linear peptide epitope bound by these
      antibodies was mapped using phage display. Both ST6 as well as the humanized anti
      CCR5 antibody ST6/34 were produced as complete IgG antibodies and shown to bind
      to cell surface CCR5.

PMID- 10969071
TI  - Tumor necrosis factor-alpha -mediated protein kinases in regulation of scavenger
      receptor and foam cell formation on macrophage.
AB  - We previously reported tumor necrosis factor-alpha (TNF) modulates
      transcriptional and post-transcriptional down-regulation of macrophage scavenger
      receptor (MSR) (Hsu, H. Y., Nicholson, A. C., and Hajjar, D. P. (1996) J. Biol.
      Chem. 271, 7767-7773); however, TNF-mediated signaling mechanisms are unknown.
      Here, we demonstrate that ligation of TNF receptor stimulates activity of p21
      activated protein kinase (PAK) and mitogen-activated protein kinases (MAPK) as
      follows: ERK, JNK, and p38 in murine macrophage J774A.1 cells. Upon activation of
      protein kinases (PK), TNF rapidly increases MSR message and protein; later it
      markedly reduces MSR expression. Studies using PK inhibitors and dominant
      negative constructs demonstrate phosphatidylinositol 3-kinase/Rac1/PAK/JNK and
      phosphatidylinositol 3-kinase/Rac1/PAK/p38 pathways contribute to important roles
      in the late stage of TNF down-regulation of MSR expression and taking up of
      OxLDL. Alternatively, the PKC/MEK1/ERK pathway in the early stage plays a
      significant role in up-regulation of the MSR gene. By using anti-TNF-R1 agonist
      antibody, we further confirm TNF-R1-mediated MAPK in regulation of MSR.
      Furthermore, in MSR gene promoter-driven luciferase reporter assays with TNF, PKC
      activator increases, but antioxidant N-acetylcysteine, PK inhibitors, and
      dominant negative constructs decrease luciferase activity in MSR gene promoter
      transfected cells. Our current results show the first evidence of crucial roles
      for TNF-mediated MAPK pathways in the transcriptional regulation of MSR gene and
      increase MSR expression; in contrast, with TNF longer treatment the pathways down
      regulate MSR and foam cell formation probably via post-transcriptional process.

PMID- 10969072
TI  - Surface-accessible residues in the monomeric and assembled forms of a bacterial
      surface layer protein.
AB  - The S-layer protein SbsB of the thermophilic, Gram-positive organism Bacillus
      stearothermophilus PV72/p2 forms a crystalline, porous array constituting the
      outermost component of the cell envelope. SbsB has a molecular mass of 98 kDa,
      and the corresponding S-layer exhibits an oblique lattice symmetry. To
      investigate the molecular structure and assembly of SbsB, we replaced 75 residues
      (mainly serine, threonine, and alanine), located throughout the primary sequence,
      with cysteine, which is not found in the wild-type protein. As determined by
      electron microscopy, 72 out of 75 mutants formed regularly-structured self
      assembly products identical to wild-type, thereby proving that the replacement of
      most of the selected amino acids by cysteine does not dramatically alter the
      structure of the protein. The three defective mutants, which showed a greatly
      reduced ability to self-assemble, were, however, successfully incorporated into S
      layers of wild-type protein. Monomeric SbsB mutants and SbsB mutants assembled
      into S-layers were subjected to a surface accessibility screen by targeted
      chemical modification with a 5-kDa hydrophilic cysteine-reactive polyethylene
      glycol conjugate. In the monomeric form of SbsB, 34 of the examined residues were
      not surface accessible, while 23 were classified as very accessible, and 18 were
      of intermediate surface accessibility. By contrast, in the assembled S-layers, 57
      of the mutated residues were not accessible, six were very accessible, and 12 of
      intermediate accessibility. Together with other structural information, the
      results suggest a model for SbsB in which functional domains are segregated along
      the length of the polypeptide chain.

PMID- 10969073
TI  - Tissue-specific expression patterns and fine mapping of the human kallikrein
      (KLK) locus on proximal 19q13.4.
AB  - The tissue or glandular kallikreins (KLK) are members of a highly conserved
      multigene family encoding serine proteases that are central to many biological
      processes. The rodent KLK families are large, highly conserved and clustered at
      one locus. The human KLK gene family is clustered on chromosome 19q13.3-13.4, and
      until recently consisted of just three members. However, recent studies have
      identified up to 11 new members of the KLK family that are less conserved than
      their rodent counterparts. Using a Southern blot and sequence analysis of 10 BACs
      and cosmids spanning approximately 400 kilobases (kb) either side of the original
      KLK 60-kb locus, we demonstrated that these genes also lie adjacent to this. We
      have also clarified the position of several microsatellite markers in relation to
      the extended KLK locus. Moreover, from Southern blot analysis of the cosmids and
      BACs with a degenerate oligonucleotide probe to the histidine-encoding region of
      serine proteases, we have shown that there are no other serine protease genes
      approximately 400 kb centromeric and 220 kb telomeric of the extended locus. We
      performed an extensive analysis of the expression patterns of these genes by
      poly(A)(+) RNA dot blot and reverse transcriptase-polymerase chain reaction
      analysis, and demonstrated a diverse pattern of expression. Of interest are
      clusters of genes with high prostate (KLK2-4) and pancreatic (KLK6-13) expression
      suggesting evolutionary conservation of elements conferring tissue specificity.
      From these findings, it is likely that the human KLK gene family consists of just
      14 clustered genes within 300 kb and thus is of a comparable size to the rodent
      families (13-24 genes within 310 and 480 kb, respectively). In contrast to the
      rodent families, the newest members of the human KLK family are much less
      conserved in sequence (23-44% at the protein level) and appear to consist of at
      least four subfamilies. In addition, like the rat, these genes are expressed at
      varying levels in a diverse range of tissues although they exhibit quite distinct
      patterns of expression.

PMID- 10969074
TI  - IkappaBalpha and IkappaBalpha /NF-kappa B complexes are retained in the cytoplasm
      through interaction with a novel partner, RasGAP SH3-binding protein 2.
AB  - IkappaBalpha inhibits the transcriptional activity of NF-kappaB both in the
      cytoplasm by preventing the nuclear translocation of NF-kappaB and in the nucleus
      where it dissociates NF-kappaB from DNA and transports it back to the cytoplasm.
      Cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes is
      controlled by mutual masking of nuclear import sequences of NF-kappaB p65 and
      IkappaBalpha and active CRM1-mediated nuclear export. Here, we describe an
      additional mechanism accounting for the cytoplasmic anchoring of IkappaBalpha or
      NF-kappaB/IkappaBalpha complexes. The N-terminal domain of IkappaBalpha contains
      a sequence responsible for the cytoplasmic retention of IkappaBalpha that is
      specifically recognized by G3BP2, a cytoplasmic protein that interacts with both
      IkappaBalpha and IkappaBalpha/NF-kappaB complexes. G3BP2 is composed of an N
      terminal domain homologous to the NTF2 protein, followed by an acidic domain
      sufficient for the interaction with the IkappaBalpha cytoplasmic retention
      sequence, a region containing five PXXP motifs and a C-terminal domain containing
      RNA-binding motifs. Overexpression of G3BP2 directly promotes retention of
      IkappaBalpha in the cytoplasm, indicating that subcellular distribution of
      IkappaBalpha and NF-kappaB/IkappaBalpha complexes likely results from a
      equilibrium between nuclear import, nuclear export, and cytoplasmic retention.
      The molecular organization of G3BP2 suggests that this putative scaffold protein
      might connect the NF-kappaB signal transduction cascade with cellular functions
      such as nuclear transport or RNA metabolism.

PMID- 10969075
TI  - Pulmonary surfactant proteins A and D are potent endogenous inhibitors of lipid
      peroxidation and oxidative cellular injury.
AB  - The lung is composed of a series of branching conducting airways that terminate
      in grape-like clusters of delicate gas-exchanging airspaces called pulmonary
      alveoli. Maintenance of alveolar patency at end expiration requires pulmonary
      surfactant, a mixture of phospholipids and proteins that coats the epithelial
      surface and reduces surface tension. The surfactant lining is exposed to the
      highest ambient oxygen tension of any internal interface and encounters a variety
      of oxidizing toxicants including ozone and trace metals contained within the 10
      kl of air that is respired daily. The pathophysiological consequences of
      surfactant oxidation in humans and experimental animals include airspace
      collapse, reduced lung compliance, and impaired gas exchange. We now report that
      the hydrophilic surfactant proteins A (SP-A) and D (SP-D) directly protect
      surfactant phospholipids and macrophages from oxidative damage. Both proteins
      block accumulation of thiobarbituric acid-reactive substances and conjugated
      dienes during copper-induced oxidation of surfactant lipids or low density
      lipoprotein particles by a mechanism that does not involve metal chelation or
      oxidative modification of the proteins. Low density lipoprotein oxidation is
      instantaneously arrested upon SP-A or SP-D addition, suggesting direct
      interference with free radical formation or propagation. The antioxidant activity
      of SP-A maps to the carboxyl-terminal domain of the protein, which, like SP-D,
      contains a C-type lectin carbohydrate recognition domain. These results indicate
      that SP-A and SP-D, which are ubiquitous among air breathing organisms, could
      contribute to the protection of the lung from oxidative stresses due to
      atmospheric or supplemental oxygen, air pollutants, and lung inflammation.

PMID- 10969076
TI  - The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular
      dopamine oxidation. A novel mechanism of toxicity.
AB  - Uptake of the Parkinsonism-inducing toxin, 1-methyl-4-phenylpyridinium (MPP(+)),
      into dopaminergic terminals is thought to block Complex I activity leading to ATP
      loss and overproduction of reactive oxygen species (ROS). The present study
      indicates that MPP(+)-induced ROS formation is not mitochondrial in origin but
      results from intracellular dopamine (DA) oxidation. Although a mean lethal dose
      of MPP(+) led to ROS production in identified dopaminergic neurons, toxic doses
      of the Complex I inhibitor rotenone did not. Concurrent with ROS formation,
      MPP(+) redistributed vesicular DA to the cytoplasm prior to its extrusion from
      the cell by reverse transport via the DA transporter. MPP(+)-induced DA
      redistribution was also associated with cell death. Depleting cells of newly
      synthesized and/or stored DA significantly attenuated both superoxide production
      and cell death, whereas enhancing intracellular DA content exacerbated
      dopaminergic sensitivity to MPP(+). Lastly, depleting cells of DA in the presence
      of succinate completely abolished MPP(+)-induced cell death. Thus, MPP(+)
      neurotoxicity is a multi-component process involving both mitochondrial
      dysfunction and ROS generated by vesicular DA displacement. These results suggest
      that in the presence of a Complex I defect, misregulation of DA storage could
      lead to the loss of nigrostriatal neurons in Parkinson's disease.

PMID- 10969077
TI  - An inhibitory monoclonal antibody binds at the turn of the helix-turn-helix motif
      in the N-terminal domain of HIV-1 integrase.
AB  - With the increase in our understanding of its structure and enzymatic mechanism,
      HIV-1 integrase (IN) has become a promising target for designing drugs to treat
      patients with AIDS. To investigate the structure and function of IN, a panel of
      monoclonal antibodies (mAbs) directed against HIV-1 IN was raised and
      characterized previously in this laboratory. Among them, mAbs17, -4, and -33 were
      found to inhibit IN activity in vitro. In this study, we investigated the
      interaction of N-terminal-specific mAb17 and its isolated Fab fragment with full
      length HIV-1 IN(1-288) and its isolated N-terminal, Zn(2+)-binding domain IN(1
      49). Our results show that binding of Zn(2+) to IN(1-49) stabilizes the mAb17-IN
      complex and that dimer dissociation is not required for binding of the Fab. To
      identify the epitope recognized by mAb17, we developed a protein footprinting
      technique based on controlled proteolysis and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry. Binding was mapped to a region
      within amino acids Asp(25)-Glu(35). This peptide corresponds to the end of a
      helix-turn-helix motif in the IN(1-55) NMR structure and contributes to the
      dimerization of the N-terminal domain. Antibody binding also appears to
      destabilize the N-terminal helix in this domain. A molecular model of the [IN(1
      49)](2).(Fab)(1) complex shows Fab binding across the dimer protein and suggests
      a potential target for drug design. These data also suggest that mAb17 inhibits
      integrase activity by blocking critical protein-protein interactions and/or by
      distorting the orientation of the N-terminal alpha-helix. The relevance of our
      results to an understanding of IN function is discussed.

PMID- 10969078
TI  - Phosphatidylinositol 3-kinase function is required for transforming growth factor
      beta-mediated epithelial to mesenchymal transition and cell migration.
AB  - We have studied the role of phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling
      in transforming growth factor beta (TGFbeta)-mediated epithelial to mesenchymal
      transition (EMT). In NMuMG mammary epithelial cells, exogenous TGFbeta1 induced
      phosphorylation of Akt at Ser-473 and Akt in vitro kinase activity against GSK
      3beta within 30 min. These responses were temporally correlated with
      delocalization of E-cadherin, ZO-1, and integrin beta(1) from cell junctions and
      the acquisition of spindle cell morphology. LY294002, an inhibitor of the p110
      catalytic subunit of PI3K, and a dominant-negative mutant of Akt blocked the
      delocalization of ZO-1 induced by TGFbeta1, whereas transfection of
      constitutively active p110 induced loss of ZO-1 from tight junctions. In
      addition, LY294002 blocked TGFbeta-mediated C-terminal phosphorylation of Smad2.
      Consistent with these data, TGFbeta-induced p3TP-Lux and p(CAGA)(12)-Lux reporter
      activities were inhibited by LY294002 and transiently expressed dominant-negative
      p85 and Akt mutants in NMuMG and 4T1 cells. Dominant-negative RhoA inhibited
      TGFbeta-induced phosphorylation of Akt at Ser-473, whereas constitutively active
      RhoA increased the basal phosphorylation of Akt, suggesting that RhoA in involved
      in TGFbeta-induced EMT. Finally, LY294002 and neutralizing TGFbeta1 antibodies
      inhibited ligand-independent constitutively active Akt as well as basal and
      TGFbeta-stimulated migration in 4T1 and EMT6 breast tumor cells. Taken together,
      these data suggest that PI3K-Akt signaling is required for TGFbeta-induced
      transcriptional responses, EMT, and cell migration.

PMID- 10969079
TI  - MEKK1 binds raf-1 and the ERK2 cascade components.
AB  - Mitogen-activated protein (MAP) kinase cascades are involved in transmitting
      signals that are generated at the cell surface into the cytosol and nucleus and
      consist of three sequentially acting enzymes: a MAP kinase, an upstream
      MAP/extracellular signal-regulated protein kinase (ERK) kinase (MEK), and a MEK
      kinase (MEKK). Protein-protein interactions within these cascades provide a
      mechanism to control the localization and function of the proteins. MEKK1 is
      implicated in activation of the c-Jun N-terminal kinase/stress-activated protein
      kinase (JNK/SAPK) and ERK1/2 MAP kinase pathways. We showed previously that MEKK1
      binds directly to JNK/SAPK. In this study we demonstrate that endogenous MEKK1
      binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting
      that it can assemble all three proteins of the ERK2 MAP kinase module.

PMID- 10969080
TI  - Regulation of cyclooxygenase-2 induction in the mouse uterus during
      decidualization. An event of early pregnancy.
AB  - The infertility phenotype of cyclooxygenase-2 (Cox-2)-deficient female mice
      establishes the important role of Cox-2 in pregnancy. Cox-2 deficiency results in
      defective ovulation, fertilization, implantation, and decidualization; the latter
      of which can be restored in part by the prostacyclin analog carbaprostacyclin.
      Uterine Cox-2 expression during early pregnancy shows distinct localization and
      kinetics in the uterine luminal epithelium and underlying stromal cells,
      suggesting that expression is tightly regulated. Several intracellular signaling
      cascades including ERK, p38, and JNK are implicated in vitro as critical
      components of regulated Cox-2 expression in response to mitogens, growth factors,
      and cytokines. We investigated the involvement of these signaling pathways during
      Cox-2 induction in vivo by monitoring uterine kinase activity after intraluminal
      application of a deciduogenic stimulus. Our results show that the ERK and p38
      pathways are activated in uterine preparations as early as 5-min post
      stimulation. ERK activation was sustained for several hours with a return to
      baseline levels by 4 h. p38 activation was rapid with a peak at 5-min post
      stimulation and returned to near baseline levels after 45 min. Systemic
      administration of a MEK inhibitor completely inhibited ERK activation, but did
      not affect early (2 h) luminal epithelial or late (24 h) stromal Cox-2 expression
      and only modestly affected decidualization. In contrast, administration of a p38
      inhibitor modestly inhibited early Cox-2 expression in the luminal epithelium,
      while dramatically diminishing late stromal expression. In parallel, induced
      stromal peroxisomal proliferator activated receptor-delta (PPARdelta) expression
      is blunted by p38 inhibition. p38 inhibition also significantly inhibited
      decidualization. These results suggest that p38, but not ERK, activation is
      required for induced Cox-2 and PPARdelta expression during decidualization. In
      addition, inhibition of p38 led to decreased decidualization suggesting that an
      intracrine prostanoid pathway consisting of Cox-2, prostacyclin, and PPARdelta is
      required for maintenance of early pregnancy.

PMID- 10969081
TI  - Restoration of correct splicing of thalassemic beta-globin pre-mRNA by modified
      U1 snRNAs.
AB  - The T-->G mutation at nucleotide 705 in the second intron of the beta-globin gene
      creates an aberrant 5' splice site and activates a 3' cryptic splice site
      upstream from the mutation. As a result, the IVS2-705 pre-mRNA is spliced via the
      aberrant splice sites leading to a deficiency of beta-globin mRNA and protein and
      to the genetic blood disorder thalassemia. We have shown previously that in cell
      culture models of thalassemia, aberrant splicing of beta-thalassemic IVS2-705 pre
      mRNA was permanently corrected by a modified murine U7 snRNA that incorporated
      sequences antisense to the splice sites activated by the mutation. To explore the
      possibility of using other snRNAs as vectors for antisense sequences, U1 snRNA
      was modified in a similar manner. Replacement of the U1 9-nucleotide 5' splice
      site recognition sequence with nucleotides complementary to the aberrant 5'
      splice site failed to correct splicing of IVS2-705 pre-mRNA. In contrast, U1
      snRNA targeted to the cryptic 3' splice site was effective. A hybrid with a
      modified U7 snRNA gene under the control of the U1 promoter and terminator
      sequences resulted in the highest levels of correction (up to 70%) in transiently
      and stably transfected target cells.

PMID- 10969082
TI  - Peroxisome proliferator-activated receptors and hepatic stellate cell activation.
AB  - The present study examined the roles of peroxisome proliferator-activated
      receptors (PPAR) in activation of hepatic stellate cells (HSC), a pivotal event
      in liver fibrogenesis. RNase protection assay detected mRNA for PPARgamma1 but
      not that for the adipocyte-specific gamma2 isoform in HSC isolated from sham
      operated rats, whereas the transcripts for neither isoforms were detectable in
      HSC from cholestatic liver fibrosis induced by bile duct ligation (BDL). Semi
      quantitative reverse transcriptase-polymerase chain reaction confirmed a 70%
      reduction in PPARgamma mRNA level in HSC from BDL. Nuclear extracts from BDL
      cells showed an expected diminution of binding to PPAR-responsive element,
      whereas NF-kappaB and AP-1 binding were increased. Treatment of cultured
      activated HSC with ligands for PPARgamma (10 microm 15-deoxy-Delta(12,14)-PGJ(2)
      (15dPGJ(2)); 0.1 approximately 10 microm BRL49653) inhibited DNA and collagen
      synthesis without affecting the cell viability. Suppression of HSC collagen by
      15dPGJ(2) was abrogated 70% by the concomitant treatment with a PPARgamma
      antagonist (GW9662). HSC DNA and collagen synthesis were inhibited by WY14643 at
      the concentrations known to activate both PPARalpha and gamma (>100 microm) but
      not at those that only activate PPARalpha (<10 microm) or by a synthetic
      PPARalpha-selective agonist (GW9578). 15dPGJ(2) reduced alpha1(I) procollagen,
      smooth muscle alpha-actin, and monocyte chemotactic protein-1 mRNA levels while
      inducing matrix metalloproteinase-3 and CD36. 15dPGJ(2) and BRL49653 inhibited
      alpha1(I) procollagen promoter activity. Tumor necrosis factor alpha (10 ng/ml)
      reduced PPARgamma mRNA, and this effect was prevented by the treatment with
      15dPGJ(2). These results demonstrate that HSC activation is associated with the
      reductions in PPARgamma expression and PPAR-responsive element binding in vivo
      and is reversed by the treatment with PPARgamma ligands in vitro. These findings
      implicate diminished PPARgamma signaling in molecular mechanisms underlying
      activation of HSC in liver fibrogenesis and the potential therapeutic value of
      PPARgamma ligands for liver fibrosis.

PMID- 10969083
TI  - Signaling from E-cadherins to the MAPK pathway by the recruitment and activation
      of epidermal growth factor receptors upon cell-cell contact formation.
AB  - E-cadherins are well characterized cell surface molecules expressed in epithelial
      cells, which play a major role in cell adhesion through the establishment of
      calcium-dependent homophilic interactions at sites of cell-cell contacts. They
      are also integral components of morphogenetic programs controlling the
      maintenance of the structural and functional integrity of epithelia. Accumulated
      evidence indicates that the E-cadherin-mediated cell adhesion system is highly
      regulated from inside the cells by a number of intracellular signaling pathways.
      Recently available information suggests that E-cadherins may also play a role in
      the transduction of signals from the outside of the cell to the cytoplasm.
      However, the nature of the biochemical routes regulated by E-cadherins is still
      largely unknown. In this study, we set out to explore the possibility that E
      cadherins may regulate the activity of MAPK, a key signaling pathway involved in
      cell fate decisions, upon the formation of cell-cell contacts among neighboring
      cells. By using an immortalized non-tumorigenic keratinocyte cell line, HaCat, as
      a model system, we provide evidence that the assembly of calcium-dependent
      adherens junctions leads to a rapid and remarkable increase in the state of
      activation of MAPK and that this event is mediated by E-cadherins. Furthermore,
      we found that E-cadherins stimulate the MAPK pathway through the ligand
      independent activation of epidermal growth factor receptors and the consequent
      activation of a biochemical route leading to the stimulation of MAPKs. These
      findings suggest that E-cadherins can initiate outside-in signal transducing
      pathways through the engagement of tyrosine kinase receptors for epidermal growth
      factor, thus providing a novel molecular mechanism whereby these cell adhesion
      molecules may ultimately control the fate of normal and transformed epithelial
      cells.

PMID- 10969084
TI  - Identification of potent, selective non-peptide CC chemokine receptor-3
      antagonist that inhibits eotaxin-, eotaxin-2-, and monocyte chemotactic protein-4
      induced eosinophil migration.
AB  - Eosinophils have been implicated in the pathogenesis of asthma and other allergic
      diseases. Several CC chemokines including eotaxin (CCL-11), eotaxin-2 (CCL-24),
      RANTES (CCL-5), and monocyte chemotactic protein-3 (MCP-3, CCL-7) and 4 (MCP-4,
      CCL-13) are potent eosinophil chemotactic and activating peptides acting through
      CC chemokine receptor-3 (CCR3). Thus, antagonism of CCR3 could have a therapeutic
      role in asthma and other eosinophil-mediated diseases. A high throughput,
      cellular functional screen was configured using RBL-2H3 cells stably expressing
      CCR3 (RBL-2H3-CCR3) to identify non-peptide receptor antagonists. A small
      molecule CCR3 antagonist was identified, SK&F 45523, and chemical optimization
      led to the generation of a number of highly potent, selective CCR3 antagonists
      including SB-297006 and SB-328437. These compounds were further characterized in
      vitro and demonstrated high affinity, competitive inhibition of (125)I-eotaxin
      and (125)I-MCP-4 binding to human eosinophils. The compounds were potent
      inhibitors of eotaxin- and MCP-4-induced Ca(2+) mobilization in RBL-2H3-CCR3
      cells and eosinophils. Additionally, SB-328437 inhibited eosinophil chemotaxis
      induced by three ligands that activate CCR3 with similar potencies. Selectivity
      was affirmed using a panel of 10 seven-transmembrane receptors. This is the first
      description of a non-peptide CCR3 antagonist, which should be useful in further
      elucidating the pathophysiological role of CCR3 in allergic inflammatory
      diseases.

PMID- 10969085
TI  - Mutational analysis of subunit G (Vma10p) of the yeast vacuolar H+-ATPase.
AB  - The G subunit of V-ATPases is a soluble subunit that shows homology with the b
      subunit of F-ATPases and may be part of the "stator" stalk connecting the
      peripheral V(1) and membrane V(0) sectors. When the N-terminal half of the G
      subunit is modeled as an alpha helix, most of the conserved residues fall on one
      face of the helix (Hunt, I. E., and Bowman, B. J. (1997) J. Bioenerg. Biomembr.
      29, 533-540). We probed the function of this region by site-directed mutagenesis
      of the yeast VMA10 gene. Stable G subunits were produced in the presence of Y46A
      and K55A mutations, but subunit E was destabilized, resulting in loss of the V
      ATPase assembly. Mutations E14A and K50A allowed wild-type growth and assembly of
      V-ATPase complexes, but the complexes formed were unstable. Mutations R25A and
      R25L stabilized V-ATPase complexes relative to wild-type and partially inhibited
      disassembly of V(1) from V(0) in response to glucose deprivation even though the
      mutant enzymes were fully active. A 2-amino acid deletion in the middle of the
      predicted N-terminal helix (DeltaQ29D30) allowed assembly of a functional V
      ATPase. The results indicate that, although the N-terminal half of the G subunit
      is essential for V-ATPase activity, either this region is not a rigid helix or
      the presence of a continuous, conserved face of the helix is not essential.

PMID- 10969086
TI  - Interactions of metarhodopsin II. Arrestin peptides compete with arrestin and
      transducin.
AB  - Arrestin blocks the interaction of rhodopsin with the G protein transducin
      (G(t)). To characterize the sites of arrestin that interact with rhodopsin, we
      have utilized a spectrophotometric peptide competition assay. It is based on the
      stabilization of the active intermediates metarhodopsin II (MII) and
      phosphorylated MII by G(t) and arrestin, respectively (extra MII monitor). The
      protocol involves native disc membranes and three sets of peptides 10-30 amino
      acids in length spanning the arrestin sequence. In the absence of arrestin, not
      one of the peptides by itself had an effect on the amount of MII formed. However,
      inhibition of arrestin-dependent extra MII was found for the peptides at residues
      11-30 and 51-70 (IC(50) < 100 microm) and residues 231-260 (IC(50) < 200 microm).
      A similar pattern of inhibition by arrestin peptides was seen when arrestin was
      replaced by G(t) or the farnesylated G(t)gamma C-terminal peptide. Only arrestin
      (11-30) inhibited MII.G(t) less (IC(50) = 300 microm) than phosphorylated
      MII.arrestin. We interpreted the data by competition of the arrestin peptides for
      interaction sites at rhodopsin, exposed in the MII conformation and specific for
      both arrestin and G(t). The arrestin sites are located in both the C- and N
      terminal domains of the arrestin structure.

PMID- 10969087
TI  - T lymphocyte-triggering factor of african trypanosomes is associated with the
      flagellar fraction of the cytoskeleton and represents a new family of proteins
      that are present in several divergent eukaryotes.
AB  - The trypanosome cytoskeleton consists almost entirely of microtubule-based
      structures. Although alpha- and beta-tubulin from Trypanosoma brucei have been
      well characterized, much less is known about other cytoskeleton-associated
      proteins in trypanosomes. Using biochemical fractionation, we demonstrate here
      that T lymphocyte-triggering factor (TLTF) from T. brucei is a component of the
      detergent-resistant and Ca(2+)-resistant fraction of the parasite cytoskeleton.
      This fraction contains the flagellar apparatus and a subset of cytoskeletal
      protein complexes that together function in cell motility, cytokinesis, and
      organelle inheritance. We also show that TLTF-related genes are present in
      several highly divergent eukaryotic organisms. Although the function of the
      corresponding proteins is not known, the mammalian TLTF-like gene (GAS11; growth
      arrest-specific gene 11) is up-regulated in growth-arrested cells and is a
      candidate tumor suppressor (Whitmore, S. A., Settasatian, C., Crawford, J.,
      Lower, K. M., McCallum, B., Seshadri, R., Cornelisse, C. J., Moerland, E. W.,
      Cleton-Jansen, A. M., Tipping, A. J., Mathew, C. G., Savnio, M., Savoia, A.,
      Verlander, P., Auerbach, A. D., Van Berkel, C., Pronk, J. C., Doggett, N. A., and
      Callen, D. F. (1998) Genomics 52, 325-331), suggestive of a role in coordinating
      cytoskeleton activities. Consistent with this possibility, we show that the human
      GAS11 protein contains a 144-amino acid domain that co-localizes with
      microtubules when fused to the green fluorescent protein and expressed in
      mammalian cells. These findings suggest that TLTF represents a newly defined
      protein family, whose members contribute to cytoskeleton function in species as
      diverse as protozoa and mammals.

PMID- 10969089
TI  - Identification of positive and negative determinants of malonyl-CoA sensitivity
      and carnitine affinity within the amino termini of rat liver- and muscle-type
      carnitine palmitoyltransferase I.
AB  - The extreme amino terminus and, in particular, residue Glu-3 in rat liver (L)
      carnitine palmitoyltransferase I (CPT I) have previously been shown to be
      essential for the sensitivity of the enzyme to inhibition by malonyl-CoA. Using
      the Pichia pastoris expression system, we now observe that, although mutants E3A
      (Glu-3 --> Ala) or Delta(3-18) of L-CPT I have markedly lowered sensitivity to
      malonyl-CoA compared with the wild-type protein, the mutant Delta(1-82) generated
      an enzyme that had regained much of the sensitivity of wild-type CPT I. This
      suggests that a region antagonistic to malonyl-CoA sensitivity is present within
      residues 19-82 of the enzyme. This was confirmed in the construct Delta(19-30),
      which was found to be 50-fold more sensitive than wild-type L-CPT I. Indeed, this
      mutant was >4-fold more sensitive than even the native muscle (M)-CPT I isoform
      expressed and assayed under identical conditions. This behavior was dependent on
      the presence of Glu-3, with the mutant E3A-Delta(19-30) having kinetic
      characteristics similar to those of the E3A mutant. The increase in the
      sensitivity of the L-CPT I-Delta(19-30) mutant was not due to a change in the
      mechanism of inhibition with respect to palmitoyl-CoA, nor to any marked change
      of the K(0.5) for this substrate. Conversely, for M-CPT I, a decrease in malonyl
      CoA sensitivity was invariably observed with increasing deletions from Delta(3
      18) to Delta(1-80). However, deletion of residues 3-18 from M-CPT I affected the
      K(m) for carnitine of this isoform, but not of L-CPT I. These observations (i)
      provide the first evidence for negative determinants of malonyl-CoA sensitivity
      within the amino-terminal segment of L-CPT I and (ii) suggest a mechanism for the
      inverse relationship between affinity for malonyl-CoA and for carnitine of the
      two isoforms of the enzyme.

PMID- 10969088
TI  - Kinetic characterization of glutathione reductase from the malarial parasite
      Plasmodium falciparum. Comparison with the human enzyme.
AB  - The homodimeric flavoenzyme glutathione reductase (GR) maintains high
      intracellular concentrations of the antioxidant glutathione (GSSG + NADPH + H(+)
      <--> 2 GSH + NADP(+)). Due to its central function in cellular redox metabolism,
      inhibition of GR from the malarial parasite Plasmodium falciparum represents an
      important approach to antimalarial drug development; therefore, the catalytic
      mechanism of GR from P. falciparum has been analyzed and compared with the human
      host enzyme. The reductive half-reaction is similar to the analogous reaction
      with GR from other species. The oxidative half-reaction is biphasic, reflecting
      formation and breakdown of a mixed disulfide between the interchange thiol and
      GSH. The equilibrium between the E(ox)-EH(2) and GSSG-GSH couples has been
      modeled showing that the Michaelis complex, mixed disulfide-GSH, is the
      predominant enzyme form as the oxidative half-reaction progresses; rate constants
      used in modeling allow calculation of an K(eq) from the Haldane relationship,
      0.075, very similar to the K(eq) of the same reaction for the yeast enzyme
      (0.085) (Arscott, L. D., Veine, D. M., and Williams, C. H., Jr. (2000)
      Biochemistry 39, 4711-4721). Enzyme-monitored turnover indicates that E(FADH(
      ))(S-S). NADP(+) and E(FAD)(SH)(2).NADPH are dominant enzyme species in turnover.
      Since the individual forms of the enzyme differ in their susceptibility to
      inhibitors, the prevailing states of GR in the cell are of practical relevance.

PMID- 10969090
TI  - Predicting the outcome of neonatal bacterial meningitis.
AB  - OBJECTIVE: To build predictive models of severe adverse outcome at various times
      in the course of neonatal bacterial meningitis. STUDY DESIGN: Retrospective
      cohort study with follow-up to a minimum age of 1 year of term and near-term
      infants, admitted between 1979 and 1998 to a regional tertiary care center.
      Predictors of adverse outcome detectable at 1 year of age (death or moderate or
      severe neurosensory impairment) were identified by univariate analysis.
      Independent predictors of adverse outcome were identified by multivariate
      analysis. Predictive tree models were constructed at 12, 24, 48, and 96 hours
      after admission and at discharge. RESULTS: Of 101 infants admitted with
      definitive bacterial meningitis, 13 died and 17 had moderate or severe disability
      at 1 year of age. Outcomes are known for all patients, to 1 year of age. Twelve
      hours after admission the important predictors of adverse outcome were presence
      of seizures, presence of coma, use of inotropes, and leukopenia (sensitivity:
      68%; specificity: 100%). At 96 hours the predictors were seizure duration of >72
      hours, presence of coma, use of inotropes, and leukopenia (sensitivity: 88%;
      specificity: 99%). CONCLUSIONS: Most infants at risk for adverse outcome can be
      identified within 12 hours of admission. Duration of seizures for >72 hours,
      presence of coma, use of inotropes, and leukopenia were the most important
      predictors of adverse outcome. Although these models have good predictive
      accuracy, they need to be validated in a contemporary cohort in large multicenter
      studies.

PMID- 10969091
TI  - Pacifier as a risk factor for acute otitis media: A randomized, controlled trial
      of parental counseling.
AB  - OBJECTIVES: To evaluate the association between pacifier use and the increased
      occurrence of acute otitis media (AOM) in an intervention trial. METHODS:
      Fourteen well-baby clinics were selected to participate in an open, controlled
      cohort study. These clinics were paired according to the number of children and
      the social classes of the parents they served. One clinic in each pair was
      randomly allocated for an intervention, while the other served as a control. The
      nurses at the intervention clinics were trained to instruct the parents of
      children <18 months old to limit pacifier use during their prescheduled visits to
      the clinic. The intervention consisted of a leaflet explaining the harmful
      effects of pacifier use and instructions to restrict its use. Two hundred seventy
      two children were successfully recruited from the intervention clinics and 212
      from the control clinics. The data about pacifier use and the occurrence of
      respiratory infections and AOM were collected similarly in both groups. RESULTS:
      After the intervention, a 21% decrease was achieved in continuous pacifier use at
      the age of 7 to 18 months (P =.0001), and the occurrence of AOM per person-months
      at risk was 29% lower among children at the intervention clinics. The children
      who did not use a pacifier continuously in either of the clinics had 33% fewer
      AOM episodes than the children who did. CONCLUSION: Pacifier use appeared to be a
      preventable risk factor for AOM in children. Its restriction to the moments when
      the child was falling asleep effectively prevented episodes of AOM.

PMID- 10969092
TI  - Immunization entry at the point of service improves quality, saves time, and is
      well-accepted.
AB  - OBJECTIVE: Computer-based immunization tracking is a routine part of many
      pediatric practices; however, data quality is inconsistent and entry often relies
      on dedicated data entry personnel and is time-consuming, expensive, or difficult.
      The purpose of this study was to evaluate data quality, nursing satisfaction, and
      reduction in documentation burden after the introduction of a point-of-service
      immunization entry system in an inner-city pediatric primary care center. DESIGN:
      Prospective preintervention and postintervention study. METHODS: Visit records
      from all pediatric nonurgent care visits for patients <5 years old were collected
      during a 2-week period before (preintervention) and after (postintervention) the
      introduction of a computer-based immunization entry system. Nurses used software
      designed to allow rapid entry during immunization preparation followed by
      printing 2 adhesive labels for documentation. Satisfaction was evaluated using an
      8-question survey administered 3 months after the intervention. RESULTS: One
      hundred forty-seven (63.6%) of 231 preintervention and 132 (51.4%) of 257
      postintervention children received at least 1 immunization (immunized) during the
      study visit. Gender and mean age were similar for immunized children in the 2
      groups. In the preintervention group, 56 (37.9%) of 147 immunized children had at
      least 1 dose missing (a total of 128 of 343 doses administered) from the
      immunization tracking database compared with none in the postintervention group.
      Medical record review showed that 92.6% of preintervention and 91.4% of
      postintervention children were on-schedule after the study visit. However,
      missing data lead to the misclassification of preintervention children-only 68.4%
      were reported by the database to be on-schedule. All 9 nurses reported using the
      program all the time to enter immunizations, 89% said that the program required
      somewhat or a lot less time, and 100% strongly recommended continued use of the
      program. All 9 nurses also reported that they would be somewhat or very
      unenthusiastic about the system if labels were not available. During the 12
      months after introduction of the system, 8273 forms containing immunization
      information were printed, preventing nurses from having to write >101,000 dates.
      CONCLUSIONS: Immunization entry by nurses at the time of immunization preparation
      improves the quality of tracking data, reduces misclassification of immunization
      needs, saves time, and can be well-accepted. It is likely that poor data quality
      in some tracking systems has led to falsely low immunization coverage estimates.
      Systems such as the one in this study can improve quality and should be
      integrated into routine clinical practice.

PMID- 10969093
TI  - Determination of up-to-date vaccination status for preschool-aged children: how
      accurate is manual assessment conducted by paraprofessional staff?
AB  - BACKGROUND: Accurate identification of underimmunized children is needed to
      determine which children need vaccination. Previous studies have found the
      accuracy of manually determining the immunization status from a personal
      vaccination record to be low (<50%). OBJECTIVE: To determine the accuracy of
      manual immunization status assessment for preschool-aged children. SUBJECTS AND
      SETTING: Children </=32 months old (n = 21 263) seen over 1 year at 12 women,
      infants, and children (WIC) sites in San Diego, California. Age at evaluation was
      between 0 and 24 months. METHODS: Paraprofessional immunization specialists
      conducted manual immunization status assessment using the WIC client's personal
      vaccination record. Immunization status as recorded in the WIC record was
      compared with computerized assessment (the gold standard). MEASURES AND RESULTS:
      For all patient encounters, 29 078 (80%) of 36 368 were assessed correctly;
      manual assessment outcome was not recorded in the WIC record for 2171 (6%) of
      encounters. Accuracy varied by WIC site (range: 70%-90%). The sensitivity at
      correctly identifying an underimmunized child per encounter was 53.6%; the
      specificity at correctly identifying a fully vaccinated child per encounter was
      89. 4%. The 3 most common vaccines that were incorrectly assessed in identifying
      an underimmunized child were Haemophilus influenzae type b (43%), hepatitis B
      (37%), and diphtheria-tetanus toxoids and (cellular or acellular) pertussis
      vaccine (24%). Children with no outcome as recorded in the WIC record were 5
      times as likely to be up-to-date. CONCLUSIONS: Manual immunization assessment was
      specific but only moderately sensitive at identifying underimmunized children.
      Thus, many underimmunized children will by missed but only 10% of children will
      be referred inappropriately.

PMID- 10969094
TI  - Clinical performance of an in-line point-of-care monitor in neonates.
AB  - OBJECTIVE: To evaluate the bias, precision, and blood loss characteristics of an
      ex vivo in-line point-of-care testing blood gas and electrolyte monitor designed
      for use in critically ill newborn infants. STUDY DESIGN: Study participants
      included consecutive neonates with an umbilical artery catheter (UAC) in use for
      clinical laboratory testing. The in-line monitor (VIA LVM Blood Gas and Chemistry
      Monitoring System, VIA Medical, San Diego, CA) was directly connected to the
      participant's UAC and the monitor's determinations of pH, PCO(2), PO(2), sodium,
      potassium, and hematocrit (Hct) were compared with those simultaneously drawn and
      measured with a standard bench top laboratory instrument (Radiometer 625 ABL;
      Radiometer America, Inc, Westlake, OH). The bias (the mean difference from the
      reference method) and precision (1 standard deviation of the mean difference)
      performance criteria of the in-line monitor were derived using standard
      laboratory procedures. RESULTS: Sixteen neonates monitored for a total of 37 days
      had a total of 229 paired blood samples available for comparison by the 2
      methods. Bias and precision performance characteristics of the in-line monitor
      were similar to reports of other point-of-care devices (ie, pH: -.003 +/-.024;
      PCO(2):.35 +/- 2.84 mm Hg; PO(2):.39 +/- 7.30 mm Hg; sodium:.52 +/- 2.34 mmol/L;
      potassium:.17 +/-.18 mmol/L; and Hct:.61 +/- 2.80%). The range of values observed
      for each parameter included much of the range anticipated among critically ill
      neonates (ie, pH: 7.15-7.65; PCO(2): 25-75 mm Hg; PO(2): 25-275 mm Hg; sodium:
      127-150 mmol/L; potassium: 2.6-5.5 mmol/L; and Hct: 32%-60%). Mean blood loss (+/
      standard deviation) per sample with the in-line monitor was approximately one
      tenth that of the reference method: 24 +/- 7 microL versus 250 microL,
      respectively. There was no evidence of hemolysis and no patient related safety
      issues were identified with use of the in-line monitor. CONCLUSIONS: Repeated
      laboratory testing of critically ill neonates using an ex vivo in-line monitor
      designed for use in neonates provides reliable laboratory results. The blood loss
      and hemolysis data obtained suggests that this monitoring device offers potential
      for reducing neonatal blood loss-and possibly transfusion needs-during the first
      weeks of life. Before this promising technology can be routinely recommended for
      care of critically ill neonates, greater practical experience in a variety of
      clinical settings is needed.

PMID- 10969095
TI  - Occult bacteremia from a pediatric emergency department: current prevalence, time
      to detection, and outcome.
AB  - OBJECTIVE: To evaluate selected characteristics of occult bacteremia in the post
      Haemophilus influenzae type b (HIB) vaccine era. METHODS: A retrospective cohort
      study was performed involving 5901 children 2 to 24 months old with fever >/=39.0
      degrees C evaluated with a blood culture at an urban tertiary care children's
      hospital emergency department (ED) between February 1993 and June 1996. Patients
      were excluded if immune-suppressed, diagnosed with a focal infection, evaluated
      by lumbar puncture, or admitted to the hospital during initial evaluation.
      Prevalence of occult bacteremia, distribution of current pathogenic organisms,
      and time to positive culture in a continuously monitored system were determined.
      All patients with cultures positive for pathogenic bacteria were reevaluated and
      serious adverse outcomes were documented. RESULTS: The prevalence of occult
      bacteremia was 1.9% (95% confidence interval: 1.5%-2.3%). Streptococcus
      pneumoniae accounted for 82.9% of all pathogens and H influenzae was not a
      causative organism in this cohort. The mean time to positive culture was
      significantly shorter for pathogens compared with contaminants (14.9 hours vs
      31.1 hours). A culture that was positive in </=18 hours was 13.0 (6.3-26. 6)
      times more likely to contain a pathogen than a contaminant. The average time from
      positive culture notification to reevaluation in the ED was 10.6 hours and over
      half of the patients recalled to the ED for positive cultures were admitted to
      the hospital. Of patients with occult pneumococcal bacteremia, 95.7% had
      resolution of their bacteremia without the use of parenteral antibiotics. Two
      patients had serious adverse outcomes. The rate of meningitis or death was. 03%
      (.004%-.12%). The contamination rate of blood cultures was 2.1% (1.7%-2.5%). Most
      (85%) of these patients were reevaluated in the ED and more than one third were
      admitted to the hospital before full identification of the organism. CONCLUSIONS:
      Prevalence of occult bacteremia in the post-HIB vaccine era is lower than
      previously reported. S pneumoniae is the most common causative organism and
      resolves without parenteral antibiotics in the vast majority of cases.
      Continuously monitoring blood culture systems allow for early identification and
      can aid in differentiating contaminated from true pathogenic cultures by time to
      positive culture. Serious adverse outcome is an uncommon result of occult
      bacteremia. Updated epidemiology and microbiologic technology may impact the
      evaluation and treatment of children at risk for occult bacteremia.

PMID- 10969096
TI  - Barriers to asthma care in urban children: parent perspectives.
AB  - BACKGROUND: Despite improved treatment regimens for asthma, the prevalence and
      morbidity from asthma are increasing, especially among underserved, minority
      children. OBJECTIVE: The purpose of this study was to identify barriers to the
      treatment of asthma among urban, minority children as perceived by parents.
      METHODS: Parents were recruited from 4 schools located in low-income, urban areas
      with high rates of asthma hospitalizations. Focus groups involving parents of
      children 5 to 12 years old with asthma were conducted using a standardized
      questionnaire. Parents' comments were analyzed to identify barriers, and 3
      independent raters coded parents' comments to assess reliability of
      interpretation. RESULTS: Forty parents who represented 47 children participated
      in the focus groups. All parents described their racial background as black.
      Parents' average age was 36.8 years, 92% were females, 70% were nonmarried, and
      38% had less than a high school education. Forty-five percent of children had
      intermittent or mild asthma and 55% had moderate to severe asthma. The most
      frequent types of barriers identified by parents were patient or family
      characteristics (43%), followed by environmental (28%), health care provider
      (18%), and health care system (11%). Parents were specifically concerned about
      the use, safety and long-term complications of medications, the impact of
      limitation of exercise on their child's quality of life, and their own quality of
      life. CONCLUSIONS: In contrast with the widespread beliefs that access to medical
      care, health insurance, and continuity of care are the major barriers to quality
      asthma care, the barriers most frequently reported by parents were related to
      patient and family characteristics, health beliefs, or to their social and
      physical environment. To improve asthma management and health outcomes for urban,
      minority children with asthma, it is critical to tailor education about asthma
      and its treatment, and address quality of life issues for both children and
      parents.

PMID- 10969097
TI  - Nosocomial respiratory syncytial virus infections: the cost-effectiveness and
      cost-benefit of infection control.
AB  - OBJECTIVE: To determine the cost-effectiveness and cost-benefit of an infection
      control program to reduce nosocomial respiratory syncytial virus (RSV)
      transmission in a large pediatric hospital. DESIGN: RSV nosocomial infection (NI)
      was studied for 8 years, before and after intervention with a targeted infection
      control program. The cost-effectiveness of the intervention was calculated, and
      cost-benefit was estimated by a case-control comparison. SETTING: Children's
      Hospital of Philadelphia, a 304-bed pediatric hospital. PATIENTS: All inpatients
      with RSV infection, both community- and hospital-acquired. INTERVENTION:
      Consisted of early recognition of patients with respiratory symptoms,
      confirmation of RSV infection by laboratory testing, establishing cohorts of
      patients and nursing staff, gown and glove barrier precautions, and monitoring
      and education of staff. OUTCOME MEASURES: The incidence density of RSV NI before
      and after the intervention was calculated as the rate per 1000 patient days-at
      risk for infection. Intervention costs included laboratory testing, isolation,
      and administration of the program. The cost of RSV NI was estimated by comparing
      hospital charges for 30 cases and matched uninfected controls. RESULTS: A total
      of 148 patients acquired NI (88 before and 60 after the intervention). The Mantel
      Haenszel stratified relative risk for NI in the period before the infection
      control program, compared with the postintervention period, was.61 (95%
      confidence interval:.53-.69). By applying the preintervention stratum-specific
      rates of infection to the days-at-risk in the postintervention period, an
      estimated 100 NIs would have been expected, which in comparison to the 60 NIs
      observed, yielded an estimated program effectiveness of 10 RSV NIs prevented per
      season. The total cost of the program per season was $15 627 or $1,563/NI
      prevented. In comparison, the mean cost to the hospital was $9,419/case of RSV
      NI, resulting in a cost-benefit ratio of 1:6. CONCLUSIONS: A targeted infection
      control intervention was cost-effective in reducing the rate of RSV NI. For every
      dollar spent on the program, approximately $6 was saved.

PMID- 10969098
TI  - Neuroimaging in children with newly diagnosed epilepsy: A community-based study.
AB  - BACKGROUND: Neuroimaging is generally considered a part of the evaluation of
      seizures and epilepsy. There is limited information about its current use in the
      initial evaluation of pediatric epilepsy and about its yield during the initial
      diagnosis of epilepsy. We describe the patterns in the use and yield of
      diagnostic imaging in children with newly diagnosed epilepsy in a community-based
      study. METHODS: Children were recruited when first diagnosed with epilepsy by
      participating physicians in Connecticut (1993-1997). Definitions for etiology and
      underlying epilepsy syndromes are as published by the International League
      Against Epilepsy. RESULTS: Of 613 children, 488 (79.6%) had imaging: 388 (63. 3%)
      magnetic resonance imaging, 197 (32.1%) computed tomography scans, and 97 (15.8%)
      both. Half of children with idiopathic generalized epilepsy had imaging studies
      compared with 70% to 100% of children with other forms of epilepsy, depending on
      the specific type. Etiologically relevant abnormalities were found in 62 (12.7%
      of those imaged). Fourteen of these children had otherwise completely normal
      presentations and histories. Their abnormalities included tuberous sclerosis (N =
      4), tumors (N = 2), an arteriovenous malformation later diagnosed as a tumor, a
      cavernous angioma, cerebral malformations (N = 3), and other abnormalities (N =
      3). Thirteen of the 14 had partial seizures and 12 had focal
      electroencephalographic (EEG) findings. Only 1 had neither. CONCLUSIONS: In
      children with newly diagnosed epilepsy, neuroimaging reveals a small but
      significant number of serious abnormalities not previously suspected. Most of
      these children have partial seizures or focal EEG abnormalities. Neuroimaging
      should be considered during the evaluation of children with newly diagnosed
      epilepsy, especially for those with neurologic deficits or partial seizures or
      focal EEG abnormalities that are not part of an idiopathic localization-related
      epilepsy syndrome.

PMID- 10969099
TI  - Stimulant treatment in Maryland public schools.
AB  - OBJECTIVE: A statewide school survey was performed to provide naturalistic data
      on the prevalence of medication administered to Maryland public school students
      for the treatment of attention deficit hyperactivity disorder (ADHD) to clarify
      the concern of some state legislators about stimulant treatment for youths.
      METHODS: In April 1998, school nurses supervised a survey of all Maryland public
      school students medicated during school hours for ADHD. The data collected on
      these students included: type of medication administered, gender, school level,
      race/ethnicity, special education and Section 504 status, and the specialist of
      the prescriber. RESULTS: Of the 816 465 students surveyed, 20 050 (2. 46%)
      received methylphenidate and 3721 (0.46%) received other medications for ADHD.
      Other major findings were: 1) methylphenidate constituted 84% of all the
      medication administered for ADHD; 2) the male:female ratio of the medication's
      recipients was 3.5:1 and 4.3:1 in elementary and secondary school, respectively;
      3) black and Hispanic students received methylphenidate at approximately half the
      rate of their white counterparts; 4) 45% of all students receiving
      methylphenidate had special education status and an additional 8% had Section 504
      status; and 5) nurse practitioners were the prescribers of 3% of the
      methylphenidate prescribed to Maryland students. CONCLUSIONS: This large,
      population-based, point prevalence study of medication administered to students
      for ADHD adds new and updated findings on prevalence variations, rates for
      minority and special education/Section 504 students, and specialty prescriber
      rates.

PMID- 10969100
TI  - Effects of negative life events on immune suppression in children and youth
      infected with human immunodeficiency virus type 1.
AB  - OBJECTIVES: To evaluate the association of negative stressful life events
      experienced over 12 months and the risk of moderate to severe immune suppression
      among children and youth infected with human immunodeficiency virus type 1 (HIV
      1). METHODS: Longitudinal study of 618 HIV-1-infected children, baseline ages 1
      to 20 years (mean age: 6.4 years), who completed 52 weeks of participation in the
      Pediatric Late Outcomes Study (Pediatric AIDS Clinical Trials Group Protocol
      219). Severity of immune suppression was indicated by the Centers for Disease
      Control and Prevention Pediatric HIV Disease Classification System, based on CD4
      percentages. The total number of negative life events-categorized as none, 1, or
      >1 life event reported as having occurred in the previous 12 months (previous 6
      months for children <3 years of age)-was the predictor variable. Multiple
      logistic regressions were estimated to assess the relationship of negative life
      events and immune suppression at outcome, controlling for baseline measures of
      immune suppression, continuous CD4%, negative life events, age, race/ethnicity,
      gender, primary caretaker, education level of caretaker, and acquired
      immunodeficiency syndrome status. RESULTS: At week 52, 379 subjects (61% of total
      study population) had moderate to severe immune suppression. Of 275 children with
      normal immune function at baseline, 68 (24.7%) subsequently developed moderate to
      severe suppression levels by week 52 of follow-up. Of 343 children with immune
      suppression at baseline, 32 (9.2%) had recovered to normal CD4% levels by week
      52. More than 1 negative life event was associated with an increased risk
      (prevalence) of immune suppression (odds ratio [OR]: 2.76; 95% confidence
      interval [CI]: 1.44,5.31), controlling for baseline CD4%, total life events, and
      other covariates. Children without immune suppression at baseline who experienced
      >1 negative life event had an increased incidence of immune suppression (OR:
      2.93; 95% CI: 1.34,6.39), controlling for baseline covariates. CONCLUSIONS:
      Results indicate that negative stressful life events increase the risk of
      children with HIV-1 infection having impaired immune function. Further research
      is needed to identify potential mechanisms of the relationship between stressful
      life events and impaired immune function. These mechanisms include
      psychoneuroendocrinologic response and difficulties in adherence to therapy after
      exposure of a child to major negative life events.

PMID- 10969101
TI  - Vitamin A status and postnatal dexamethasone treatment in bronchopulmonary
      dysplasia.
AB  - OBJECTIVE: Vitamin A (retinol) plays an important role in epithelial regeneration
      during recovery from lung injury in bronchopulmonary dysplasia (BPD).
      Dexamethasone is used in the postnatal treatment of very low birth weight (VLBW)
      neonates with BPD. To test the hypothesis that the vitamin A status is critical
      for the beneficial pulmonary response to dexamethasone, we performed a
      prospective cohort study in which we characterized the changes in plasma
      concentrations of vitamin A and retinol-binding protein (RBP) in response to
      dexamethasone, and correlated these changes with the pulmonary outcome. METHODS:
      VLBW neonates (birth weight <1350 g, gestational age <31 weeks, postnatal age >10
      days), who had presumptive diagnosis of severe BPD and need for high ventilatory
      support (fraction of inspired oxygen >/=.6, mean airway pressure >/=7 cm H(2)O),
      were treated with a seven-day course of dexamethasone (.5 mg/kg/d x 2 days,.25
      mg/kg/d x 2 days,.1 mg/kg/d x 3 days). Plasma concentrations of vitamin A and RBP
      were determined sequentially at baseline, and during and after dexamethasone
      treatment. Pulmonary response to dexamethasone was graded daily using a composite
      ventilation score. The changes in plasma vitamin A and RBP concentrations were
      compared between infants with a positive (beneficial) pulmonary response to
      dexamethasone and those with a negative response. RESULTS: Among 23 infants
      studied, 13 showed a positive pulmonary response to dexamethasone, as indicated
      by successful weaning from supplemental oxygen and mechanical ventilation,
      whereas 10 showed a negative response. A significant, yet short-term, increase in
      plasma concentrations of both vitamin A and RBP was observed in most infants
      treated with dexamethasone. The plasma vitamin A and RBP responses to
      dexamethasone tended to be higher in infants with a positive pulmonary response
      than in those with a negative response. Accounting for gender, a vitamin A
      response with each 10.0 microg/dL increment in plasma vitamin A concentration was
      associated with a 60% increase in the odds favoring a positive pulmonary response
      to dexamethasone. CONCLUSION: Postnatal dexamethasone treatment in VLBW neonates
      with BPD induces a significant, yet short-term, increase in plasma concentrations
      of both vitamin A and RBP. This increase probably results from endogenous
      mobilization of vitamin A from the liver. Our data suggest that the beneficial
      pulmonary response to dexamethasone in infants with BPD is influenced, at least
      in part, by the vitamin A status, and that gender plays a role in this
      response.vitamin A, dexamethasone, bronchopulmonary dysplasia.

PMID- 10969102
TI  - Functional limitations and special health care needs of 10- to 14-year-old
      children weighing less than 750 grams at birth.
AB  - OBJECTIVE: To examine the health status, functioning, and special health care
      needs of children 10 to 14 years old weighing <750 g at birth. METHODS: We
      compared outcomes of a regional cohort of 59 children born from 1982 through 1986
      weighing <750 g at birth (mean: 665 g; gestational age: 26 weeks) to matched
      groups of 54 children weighing 750 to 1499 g at birth and 49 children born at
      term. Assessments of limitations in functioning, compensatory dependence and
      needs for services above routine, at a mean age of 11 years, were based on
      responses to maternal questionnaires. Rates of these outcomes were compared
      between groups using logistic regression analyses that controlled for gender and
      social risk. RESULTS: Children weighing <750 g at birth had significantly higher
      rates of functional limitations, greater compensatory dependence, and need for
      services above routine than the other 2 groups. Compared with children born at
      term, the odds ratio for mental or emotional delay was 4.7 (95% confidence
      interval [CI]: 2.0-11.0), for restrictions in activity, 5.1 (CI: 1.6-16.3) and
      for blindness or difficulty seeing 3.9 (CI:1.3-11.4). With the exception of 3% of
      children who were severely impaired, the only compensatory aid that
      differentiated the children weighing <750 g at birth from the children born at
      term was the greater need for glasses (odds ratio [OR]: 2.8 [CI: 1.3-6.3]).
      Increased services above routine included special education (OR: 5.0 [CI: 2.1
      11.7]), counseling (OR: 4.8 [CI: 1.0-23.1]) and special arrangements in school
      (OR: 9.5 [C.I. 2.1-43. 6]). CONCLUSION: Parents and educators need to be informed
      of the potential for disability and special health care needs of children
      weighing <750 g at birth.

PMID- 10969103
TI  - Effect of prenatal steroids on potassium balance in extremely low birth weight
      neonates.
AB  - OBJECTIVE: Potassium is the most abundant intracellular cation and plays an
      important role in a variety of cell functions. Potassium homeostasis and
      regulation are important aspects of fluid and electrolyte homeostasis in
      extremely low birth weight (ELBW) infants. Because prenatal steroid (PNS)
      treatment promotes maturation of many epithelial cell systems, we sought to
      determine whether PNS affects potassium homeostasis in ELBW infants (<1000 g)
      during the first week of life. METHOD: Serum potassium (SK) concentration,
      potassium intake and output, and renal clearance were collected prospectively
      each day during the first week of life. Infants whose mothers received a full
      course of steroids before delivery (PNS group: n = 16) were compared with those
      infants whose mothers did not receive steroids (nonsteroid group [NSG]: n = 14).
      The decision to treat with PNS was made entirely by the obstetric staff in a
      nonrandomized manner. Potassium intake and excretion and serum and urine
      electrolytes were measured every 12 hours, and urine output was monitored every 2
      to 3 hours. Hyperkalemia was defined as SK >6. 5 mmol/L in a nonhemolyzed sample
      on at least 1 measurement from a central line. RESULTS: There were no significant
      differences between the groups in gestational age, Apgar score, and birth weight.
      SK increased initially after birth in the absence of exogenous K intake in all
      infants, then subsequently decreased and stabilized by day 4 of life. The peak SK
      was significantly lower in the PNS group than in the NSG group (5.2 +/-.2 mmol/L
      vs 6.2 +/-.4 mmol/L). Moreover, the peak SK was higher than 6.5 mmol/L in 70% of
      the NSG infants and in none of the PNS group. Hyperkalemia occurred in the NSG
      infants within the first 2 days when urine output was significantly lower than in
      PNS infants. SK peaked in the absence of potassium intake with similar potassium
      excretion in both groups. PNS infants had similar cumulative potassium intake
      with a lower cumulative potassium excretion than did NSG infants. PNS infants had
      a significantly less negative potassium balance than did NSG infants by day 7 of
      life (-1.0 mmol/kg vs -7.0 mmol/kg). There was no statistical difference in the
      daily serum creatinine levels, fractional excretion of potassium, and in the
      daily creatinine clearance between the 2 groups. CONCLUSION: We conclude that
      treatment with PNS prevents the nonoliguric hyperkalemia known to occur in ELBW
      neonates. We speculate that PNS induces upregulation of cell membrane sodium,
      potassium-adenosinetriphosphatase activity in the fetus. The differences in
      negative potassium balance may be accounted for by stabilization of cell
      membranes that may result in a decrease in potassium shift from intracellular to
      extracellular compartments.

PMID- 10969105
TI  - Infant sleep position policies in licensed child care centers after back to sleep
      campaign.
AB  - BACKGROUND: Since the Back to Sleep (BTS) campaign was initiated in 1994, the
      rate of prone sleeping has decreased to approximately 20%. However, child care
      centers may have an increased rate of prone sleeping in infants. In 1996, a study
      of licensed child care centers demonstrated that 43% were unaware of the
      association between sudden infant death syndrome (SIDS) and prone sleeping and
      that 49% positioned infants prone. OBJECTIVE: To determine effectiveness of a
      mailing from the BTS campaign to licensed child care centers by assessing the
      following: 1) child care center awareness of the recommendations of the American
      Academy of Pediatrics regarding infant sleep position and 2) implementation of
      the recommendations of the American Academy of Pediatrics in child care center
      practice. DESIGN: A descriptive, cross-sectional survey of licensed child care
      centers in the metropolitan Washington, DC, region. All licensed child care
      centers caring for infants <6 months old in Washington, DC, and Montgomery,
      Prince Georges, Howard, Anne Arundel, Frederick, and Charles Counties in Maryland
      were recruited for the study. RESULTS: Out of 236 eligible centers, 172 completed
      the survey. Seventy-five percent (129) of the centers were aware of
      recommendations regarding infant sleep position. Infants were placed prone in
      27.9% of centers, although only 2.9% placed infants exclusively in the prone
      position. The most common reasons for avoiding prone position entirely were SIDS
      risk reduction and licensing regulations. Half of the centers had a written
      policy regarding sleep position. Twenty centers who were aware of the dangers of
      prone sleeping continued to placed infants prone at least some of the time,
      largely because of parental request. Only 56.9% of centers had heard of the BTS
      campaign despite the mass mailing. The mailing resulted in policy change for 14
      centers. CONCLUSIONS: Since 1996, the percentage of licensed child care centers
      in the greater Washington, DC, area that are aware of the association between
      SIDS and infant sleep position has increased from 57% to 75%. In addition, the
      rate of placing infants prone in these centers has declined from 49% in 1996 to
      27.9% in this study. When child care centers are aware of the risk of prone
      sleeping, the most likely reason for continued prone placement is parental
      request. Although media and mailings have been largely effective in communicating
      BTS information to many child care centers, nonprone positioning is not universal
      among child care providers. Additional educational efforts toward child care
      providers and parents remain necessary.

PMID- 10969104
TI  - Apolipoprotein epsilon2 allele is associated with an anti-atherogenic lipoprotein
      profile in children: The Columbia University BioMarkers Study.
AB  - OBJECTIVE: We examined associations between allelic variation in the apo epsilon
      gene, which codes for apolipoprotein E, and plasma lipid levels in children.
      MATERIALS AND METHODS: We analyzed genotype and fasting lipid levels, including
      lipid particle size by nuclear magnetic resonance spectroscopy, in 515 children
      from 297 families. RESULTS: Children carrying the apo epsilon2 allele (1 or 2
      epsilon2 alleles; n = 45) had higher mean high-density lipoprotein (HDL)
      cholesterol level (49.5 +/- 13.0 vs 42.4 +/- 8.9 mg/dL) and lower mean low
      density lipoprotein (LDL) cholesterol level (82.2 +/- 48.6 vs 105.9 +/- 45.0
      mg/dL) compared with apo epsilon3/epsilon3 children (n = 322). Mean HDL size was
      larger and mean level of the atheroprotective large HDL subpopulation was higher
      among apo epsilon2 carriers compared with epsilon3/epsilon3 children (9.5 +/- 0.4
      vs 9.3 +/-.4 nm, and 32.8 +/- 9.9 vs 27.6 +/- 8.2 mg/dL). In multivariate models
      adjusting for age, sex, ethnicity, family history, body mass index, and fasting
      triglyceride level, the apo epsilon2 allele was independently predictive of
      higher levels of HDL cholesterol and the large HDL subpopulation and of lower
      level of LDL cholesterol. CONCLUSION: The apo epsilon2 allele is associated with
      an anti-atherogenic lipid pattern in children.apolipoprotein epsilon, children,
      cholesterol.

PMID- 10969106
TI  - Enhanced growth of preterm infants fed a new powdered human milk fortifier: A
      randomized, controlled trial.
AB  - OBJECTIVE: A prospective, double-blind, randomized, controlled trial was
      conducted to evaluate the growth and nutritional status of preterm infants
      receiving preterm human milk supplemented with a newly formulated powdered human
      milk fortifier (HMF), study fortifier (SF), or a powdered commercial HMF (CF).
      METHODS: Infants (n = 144) with a birth weight </=1600 g and gestational age at
      birth of </=33 weeks were enrolled and randomized before 21 days of life. Study
      day (SDAY) 1 was defined as the day full-strength fortification (4 packets/100
      mL) began and the infant reached an intake of at least 100 mL/kg/day. Growth,
      biochemical indices of nutritional status, enteral intake, feeding tolerance,
      clinical histories, and morbidity were assessed serially. The primary outcome
      variable was weight gain (g/kg/day) from SDAYs 1 to 29 or hospital discharge,
      whichever came first. RESULTS: Infants fed human milk supplemented with SF
      consistently grew more rapidly from SDAYs 1 to 29 (or hospital discharge),
      regardless of whether the statistical analyses were performed on all subjects who
      were randomized into the study and reached SDAY 1 (intent-to-treat) or were
      limited to those able to adhere strictly to the feeding protocol of the study
      (subgroup). Using mean values adjusted for study site (least square [LS] means),
      the weight gain differences were 2.6 and 3.8 g/kg/day for the intent-to-treat and
      subgroup analyses, respectively. Likewise, the length-gain differences were.14
      and.18 cm/week for the intent-to-treat and subgroup analyses, respectively.
      Infants in the SF group reached a weight of 1800 g at SDAY 18, and those in the
      CF group at SDAY 25. Mean alkaline phosphatase values among infants in the SF
      group were higher than for the CF infants (eg, LS means: 327 U/L vs 272 U/L,
      intent-to-treat analysis), likely reflecting the more rapid linear growth of the
      SF infants. Mean serum calcium values tended to be lower in the SF group in the
      intent-to-treat analysis and were significantly lower in the subgroup analysis
      (LS means: 10.3 mg/dL vs 11.2 mg/dL). Both fortifiers were generally well
      tolerated, although an increased number of infants in the CF group exited the
      feeding protocol because of gastric residuals and abdominal distention.
      CONCLUSION: A new powdered HMF was shown to enhance the growth of preterm
      infants, compared with a commercially available powdered HMF in the United
      States.

PMID- 10969108
TI  - Functional hyperactivity of hepatic glutamate dehydrogenase as a cause of the
      hyperinsulinism/hyperammonemia syndrome: effect of treatment.
AB  - OBJECTIVE: The combination of persistent hyperammonemia and hypoketotic
      hypoglycemia in infancy presents a diagnostic challenge. Investigation of the
      possible causes and regulators of the ammonia and glucose disposal may result in
      a true diagnosis and predict an optimum treatment. PATIENT: Since the neonatal
      period, a white girl had been treated for hyperammonemia and postprandial
      hypoglycemia with intermittent hyperinsulinism. Her blood level of ammonia varied
      from 100 to 300 micromol/L and was independent of the protein intake. METHODS:
      Enzymes of the urea cycle as well as glutamine synthetase and glutamate
      dehydrogenase (GDH) were assayed in liver tissue and/or lymphocytes. RESULTS: The
      activity of hepatic GDH was 874 nmol/(min.mg protein) (controls: 472-938). Half
      maximum inhibition by guanosine triphosphate was reached at a concentration of
      3.9 micromol/L (mean control values:.32). The ratio of plasma glutamine/blood
      ammonia was unusually low. Oral supplements with N-carbamylglutamate resulted in
      a moderate decrease of the blood level of ammonia. The hyperinsulinism was
      successfully treated with diazoxide. CONCLUSION: A continuous conversion of
      glutamate to 2-oxoglutarate causes a depletion of glutamate needed for the
      synthesis of N-acetylglutamate, the catalyst of the urea synthesis starting with
      ammonia. In addition, the shortage of glutamate may lead to an insufficient
      formation of glutamine by glutamine synthetase. As GDH stimulates the release of
      insulin, the concomitant hyperinsulinism can be explained. This disorder should
      be considered in every patient with postprandial hypoglycemia and diet
      independent hyperammonemia.

PMID- 10969109
TI  - Herbal vitamins: lead toxicity and developmental delay.
AB  - A case of lead poisoning from an Indian herbal vitamin is presented. The patient
      who was developmentally delayed was given an herbal vitamin from India to
      strengthen his brain. The tablet contained large amounts of lead and mercury,
      leading to significant lead burden. Vulnerability of families and lack of
      awareness of health care professionals of dangers of unknown herbal
      supplementation are discussed.

PMID- 10969107
TI  - The importance of newborn screening.

PMID- 10969110
TI  - Human granulocytic ehrlichiosis presenting as abdominal pain.
AB  - Human granulocytic ehrlichiosis (HGE) is an emerging infectious disease that
      primarily affects adults. Typical clinical features include fever, headache, and
      myalgias. This case represents the youngest reported patient with HGE. Her
      clinical presentation was unusual in that she presented with severe abdominal
      pain. In addition, she did not develop the typical spectrum of laboratory
      abnormalities that has been reported in adults. This patient's course suggests
      that the presentation of HGE may be more varied than previously reported.

PMID- 10969111
TI  - American Academy of Pediatrics. Committee on Medical Liability. Professional
      liability coverage for residents and fellows.
AB  - The American Academy of Pediatrics first developed a policy on professional
      liability coverage for pediatricians-in-training in 1989 and subsequently
      reaffirmed its basic position with slight modification in 1993. In this latest
      iteration of the statement, the original positions have been strengthened to
      address changes in the professional liability insurance industry, the structure
      and settings of residency training, and mandated reporting to health provider
      data banks. The new policy emphasizes the need to provide pediatricians in
      training with adequate professional liability insurance coverage and to educate
      residents and fellows on the importance of adequate and uninterrupted
      professional liability coverage-both during and after residency.

PMID- 10969112
TI  - American Academy of Pediatrics. Committee on Sports Medicine and Fitness. Medical
      concerns in the female athlete.
AB  - Female children and adolescents who participate regularly in sports may develop
      certain medical conditions, including disordered eating, menstrual dysfunction,
      and decreased bone mineral density. The pediatrician can play an important role
      in monitoring the health of young female athletes. This revised policy statement
      provides updated and expanded information for pediatricians on these health
      concerns as well as recommendations for evaluation, treatment, and ongoing
      assessments of female athletes.

PMID- 10969113
TI  - International Guidelines for Neonatal Resuscitation: An excerpt from the
      Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care: International Consensus on Science. Contributors and Reviewers for the
      Neonatal Resuscitation Guidelines.
AB  - The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation
      (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based
      recommendations for neonatal resuscitation. These guidelines comprehensively
      update the last recommendations, published in 1992 after the Fifth National
      Conference on CPR and ECC. As a result of the evidence evaluation process,
      significant changes occurred in the recommended management routines for: *
      Meconium-stained amniotic fluid: If the newly born infant has absent or depressed
      respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct
      tracheal suctioning should be performed to remove meconium from the airway. *
      Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and
      ventilation: 100% oxygen is recommended for assisted ventilation; however, if
      supplemental oxygen is unavailable, positive-pressure ventilation should be
      initiated with room air. The laryngeal mask airway may serve as an effective
      alternative for establishing an airway if bag-mask ventilation is ineffective or
      attempts at intubation have failed. Exhaled CO(2) detection can be useful in the
      secondary confirmation of endotracheal intubation. * Chest compressions:
      Compressions should be administered if the heart rate is absent or remains <60
      bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling
      hands method of chest compression is preferred, with a depth of compression one
      third the anterior-posterior diameter of the chest and sufficient to generate a
      palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine
      in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be
      administered if the heart rate remains <60 bpm after a minimum of 30 seconds of
      adequate ventilation and chest compressions. Emergency volume expansion may be
      accomplished with an isotonic crystalloid solution or O-negative red blood cells;
      albumin-containing solutions are no longer the fluid of choice for initial volume
      expansion. Intraosseous access can serve as an alternative route for
      medications/volume expansion if umbilical or other direct venous access is not
      readily available. * Noninitiation and discontinuation of resuscitation: There
      are circumstances (relating to gestational age, birth weight, known underlying
      condition, lack of response to interventions) in which noninitiation or
      discontinuation of resuscitation in the delivery room may be appropriate.

PMID- 10969114
TI  - Targeted early rescue surfactant in ventilated preterm infants using the click
      test.
AB  - OBJECTIVE: To determine whether use of the click test, a rapid bedside test of
      surfactant function, results in earlier and more appropriate surfactant
      administration in ventilated preterm infants than does usual early rescue
      treatment. STUDY DESIGN: Ventilated preterm infants (n = 126) with inspired
      oxygen >/=25% and mean airway pressure >/=7 cm H(2)O were randomized in
      gestational strata (<28 weeks and 28-36 weeks) to have surfactant therapy
      determined by the click test or by usual clinical and chest radiograph criteria.
      The treatment group had the click test performed on a tracheal aspirate as soon
      as possible after intubation and, if negative or equivocal (surfactant
      deficient), surfactant was given. The control group had surfactant given as soon
      as possible based on clinical and chest radiograph diagnoses of respiratory
      distress syndrome. RESULTS: In infants of <28 weeks' gestation, use of the click
      test resulted in significantly earlier surfactant therapy (median time: 50 vs 159
      minutes) and a reduction in the number of infants receiving surfactant (48% vs
      79%). In infants of 28 to 36 weeks' gestation, there was no difference in time to
      surfactant (median time: 300 vs 268 minutes) or in the number of infants
      receiving surfactant. Neonatal morbidity and mortality were similar in click test
      and control groups. CONCLUSIONS: Use of the click test in ventilated, extremely
      premature infants results in significantly earlier and more appropriately
      targeted administration of surfactant than does early rescue therapy based on
      clinical and radiograph criteria. A randomized trial of targeted early rescue
      surfactant therapy versus prophylactic surfactant therapy in infants of <28
      weeks' gestation is warranted. The click test has the potential to improve
      clinical outcomes and reduce costs.

PMID- 10969115
TI  - Are household firearms stored safely? It depends on whom you ask.
AB  - OBJECTIVE: To determine gun storage practices in gun-owning households with
      children. DESIGN: National random digit-dial telephone survey of 2521 households
      conducted in March 1999 through July 1999. This study uses a subsample of 434
      households with children <18 years old in which a respondent reported either: 1)
      personally owning a gun, or 2) living in a gun-owning household but not owning a
      gun themselves. Respondents were asked whether any household gun was currently
      stored loaded, and, if yes, whether any gun was currently stored loaded and
      unlocked. RESULTS: Twenty-one percent of gun owners compared with 7% of non
      owners reported that a household gun was stored loaded, while 9% and 2%,
      respectively, reported that a household gun was stored loaded and unlocked. Non
      gun owners were significantly more likely than were gun owners to be female (87%
      vs 22%) and to report that they lived in a house with only 1 gun (70% vs 57%) and
      no handguns (51% vs 31%). Based on the reports of actual gun owners (n = 252),
      households with children <13 years old were significantly less likely to store a
      gun loaded and unlocked (multivariate odds ratio:.1; 95% confidence
      interval:.0,.4) than were households with teenagers only. CONCLUSIONS: We find
      that among gun-owning households with children, non-gun owners report
      significantly lower rates of guns stored loaded and unlocked than do gun owners.
      These findings are consistent with recent studies that have found that married
      men are far more likely to report household gun ownership than are married women,
      and that gun users are far more likely to report that a gun is stored loaded or
      loaded and unlocked than are never users. Our findings suggest that non-gun
      owners, the vast majority of whom are women (87%), may be unaware that guns in
      their homes are stored in a manner that experts agree is unsafe. Our findings
      reinforce the importance of many pediatricians' current efforts to offer
      anticipatory guidance about firearms to gun-owning families, and, in addition,
      suggest that this guidance can be adapted depending on whether the physician is
      speaking with a gun-owning or non-gun-owning parent. In particular, because gun
      owners (mostly fathers) are less likely to bring children to the pediatrician's
      office than are non-owners (mostly mothers), physicians should take advantage of
      any opportunities that they have to address gun-related issues with parents who
      personally own guns. More commonly, physicians can encourage non-gun owners to
      participate more fully in household decision-making about gun storage by letting
      them know not only about recommended storage practices, but also that many non
      owners may not know how guns are actually stored in their own homes. firearm,
      storage, children, survey.

PMID- 10969117
TI  - Dose-response effect of cocaine on newborn head circumference.
AB  - OBJECTIVE: To evaluate the relationship between head circumference, birth weight,
      and cocaine dose in healthy term and near-term newborns exposed to cocaine in
      utero. METHODS: We used radioimmune assay (RIAH) of cocaine metabolite in
      maternal hair to quantify third trimester cocaine exposure in 240 healthy newborn
      infants (gestational age: >36 weeks). Cocaine exposure was categorized into 3
      levels: no exposure (n = 136), low cocaine exposure (n = 52; RIAH: 2-66 ng/10 mg
      hair), and high cocaine exposure (n = 52; RIAH: 81-4457 ng/10 mg hair). We
      collected information on maternal demographic characteristics, the pregnancy, and
      the use of substances through a structured interview and from the medical record.
      RESULTS: Means of birth weight, length, and head circumference of infants with
      high cocaine exposure differed significantly from those with low exposure and no
      exposure, but were similar between low exposure and no exposure. We used a
      multiple linear regression model to assess the association between newborn head
      circumference and cocaine level, adjusting for the effects of birth weight;
      gestational age; infant sex; and several maternal factors, including height,
      weight gain during pregnancy, syphilis during pregnancy, and the use of alcohol,
      cigarettes, marijuana, and opiates during pregnancy. Only birth weight, sex, and
      high cocaine exposure were significantly associated with newborn head
      circumference. The predicted head circumference deficit associated with high
      cocaine exposure (.44 cm) represents 34% of the unadjusted difference (1.28 cm)
      between mean head circumferences of infants in the high cocaine exposure and no
      exposure groups. CONCLUSION: Newborns exposed to a high level of cocaine in utero
      (RIAH: >81 ng/10 mg hair) exhibit asymmetric intrauterine growth retardation in
      which the head circumference is disproportionately smaller than would be
      predicted from the birth weight (head wasting). The deficit in head size
      associated with cocaine exposure may reflect the effects of a specific central
      nervous system insult that interferes with prenatal brain growth.

PMID- 10969116
TI  - Testing for Chlamydia and sexual history taking in adolescent females: results
      from a statewide survey of Colorado primary care providers.
AB  - OBJECTIVES: Little is known about the practice patterns of primary care providers
      as they relate to assessing risk of and screening for chlamydial infections, an
      important cause of preventable reproductive morbidity in young women in the
      United States. The present cross-sectional study was undertaken to assess levels
      of chlamydia testing, sexual history taking, and prevention practices by Colorado
      primary care physicians, nurse practitioners, and physician assistants who
      provide gynecologic care to adolescent females (13-19 years old). METHODS:
      Between July 1998 and October 1998, an anonymous, self-administered questionnaire
      was mailed to a 25% random sample (n = 1265) of Colorado physicians (family
      practitioners, internal medicine specialists, obstetrician-gynecologists, and
      pediatricians), nurse practitioners, and physician assistants. Practitioners were
      identified through professional organization membership, state-licensing bodies,
      and listings in the yellow pages. RESULTS: After estimating the eligibility rate
      among non-respondents, the adjusted response rate was 71.5%. Only 53.8% of
      providers reported regularly testing sexually active female adolescents for
      chlamydia; 71.8% of providers regularly took a sexual history. Female providers
      reported significantly higher levels of regularly taking a sexual history (87. 2%
      vs 60.6% of males), feeling comfortable discussing sex (94.4% vs 77.8%),
      discussing sexually transmitted disease (STD) prevention (81. 5% vs 71.3%), and
      testing for chlamydia (64.4% vs 38.6%). Among provider types, obstetrician
      gynecologists, nurse practitioners, and pediatricians were most likely to report
      regularly taking a sexual history (90.1%, 88.6%, and 76.0%, respectively).
      Internal medicine specialists were the least likely to report taking a sexual
      history (43.9%). Pediatricians and nurse practitioners were the most likely to
      report testing sexually active adolescent females for chlamydia (74.1% and 70.1%,
      respectively), whereas physician assistants and internal medicine specialists
      were the least likely (46.0% and 38.5%, respectively). In multivariate analysis,
      variables independently associated with regularly taking a sexual history
      included female provider gender (odds ratio [OR]: 5.5; 95% confidence interval
      [CI]: 2.9-10.9), obstetrics/gynecology specialty (OR: 4.0; 95% CI: 1.7-10. 3;
      referent group: family practitioners), and provider comfort level in discussing
      sex (OR: 4.9; 95% CI: 2.3-11.1). Variables independently associated with
      regularly testing adolescent females for chlamydia included female provider
      gender (OR: 2.8; 95% CI: 1. 6-4.8), regularly discussing STD prevention (OR: 2.1;
      95% CI: 1.1-4. 1), and regularly discussing limiting the number of patients' sex
      partners (OR: 2.4; 95% CI: 1.4-4.1). CONCLUSIONS: Only a little over one half of
      providers (54%) reported regularly performing chlamydia tests on adolescent
      females who are sexually active by history. Because this falls well short of the
      recommendations of the Centers for Disease Control and Prevention to test all
      sexually active female adolescents, efforts are needed to improve STD clinical
      practices of Colorado physician and nonphysician providers of primary care for
      adolescent females. Particular efforts are needed to close the provider gender
      gap.

PMID- 10969118
TI  - Effect of passive smoking in pregnancy on neonatal nucleated red blood cells.
AB  - OBJECTIVE: We evaluated whether the absolute nucleated red blood cell (RBC) count
      is elevated in term, appropriate for gestational age (AGA) infants born to women
      exposed to passive smoking in pregnancy. PATIENTS AND METHODS: We compared
      absolute nucleated RBC counts taken during the first 12 hours of life in 2 groups
      of term, vaginally delivered infants, 1 group born to mothers who were routinely
      exposed to tobacco smoke during pregnancy (n = 55) either at home or at the
      workplace, and the other to mothers who were not routinely exposed to any tobacco
      smoke (n = 31). We excluded infants of women with conditions known to elevate
      nucleated RBC counts. RESULTS: There were no differences between groups in birth
      weight, maternal age, gravidity, parity, maternal analgesia during labor, 1- and
      5-minute Apgar scores. Gestational age was minimally higher in the control group
      (39.6 +/- 1.1 vs 39.2 +/-.8 weeks). The median absolute nucleated RBC count in
      the passive smoking group was 357 x 10(6)/L (range: 0-5091 x 10(6)/L) versus 237
      x 10(6)/L (range: 0-1733 x 10(6)/L) in nonsmoking controls. Stepwise regression
      analysis that included Apgar scores, gestational age, and the passive smoking
      status (yes/no) as independent variables showed significant correlation of
      absolute nucleated RBC count only with the passive smoking status. CONCLUSION: At
      birth, term AGA infants born to mothers exposed to passive smoking have increased
      circulating absolute nucleated RBC counts compared with those of controls. We
      speculate that passive smoking in pregnancy should be avoided, because it may
      have subtle negative effects on fetal oxygenation.

PMID- 10969119
TI  - Distal sensory polyneuropathy in a cohort of HIV-infected children over five
      years of age.
AB  - BACKGROUND: Peripheral neuropathy in children with human immunodeficiency virus
      (HIV) infection has not been systematically studied. Objectives. To describe the
      symptoms and signs of peripheral neuropathy in HIV-infected children and to
      determine their frequency. METHODS: A cross-sectional study was conducted on a
      convenience sample from a cohort of children older than 5 years of age at the
      pediatric HIV outpatient clinic of the Federal University of Rio de Janeiro.
      Those patients were interviewed and examined systematically for peripheral nerve
      symptoms and signs. RESULTS: A total of 39 patients were clinically evaluated.
      Their ages ranged from 5 to 14 years, and 13 patients (34%) had symptoms and
      signs of peripheral nerve involvement. Distal paresthesia and/or pain plus
      diminished ankle jerks and/or diminished vibration sense were the most common
      clinical findings. Symptoms were chronic and fluctuating, and pain was, in
      general, not severe. Nerve conduction studies primarily revealed axonal changes.
      CONCLUSIONS: Peripheral neuropathy occurs in one third of HIV-infected children,
      and, in general, has less severe features than the distal sensory polyneuropathy
      described in adults. peripheral neuropathy, human immunodeficiency virus,
      children.

PMID- 10969120
TI  - Coarctation of the abdominal aorta and renal artery stenosis related to an
      umbilical artery catheter placement in a neonate.
AB  - Umbilical artery catheters have been associated with thrombotic complications,
      such as partial or complete occlusion in the aorta, the renal arteries, and other
      blood vessels. There have been few reports of the long-term consequences of
      either symptomatic or asymptomatic thrombi. We report a patient, now 22 years of
      age, born with a normal aorta, who developed hypertension at the age of 2 months
      after use of an umbilical artery catheter. An intravenous pylegram and nuclear
      renal scan were compatible with occlusion of left renal artery and of the distal
      aorta. At 6 months of age, the patient presented with reduced femoral pulses.
      Angiography demonstrated an acquired coarctation of the abdominal aorta and renal
      artery stenosis. An abdominal ultrasound performed at 22 years of age revealed
      partial obstruction of the lower abdominal aorta and marked atrophy of the left
      kidney. This case underlines the importance of long-term follow-up studies of
      infants who have undergone umbilical artery catheterizations.

PMID- 10969121
TI  - Morbid hypocalcemia associated with phosphate enema in a six-week-old infant.
AB  - A 6-week-old premature infant who was born at 29 weeks of gestation presented to
      the emergency department with a several-hour history of stiffness and increased
      alarms on his apnea monitor at home. On arrival he was noted to have generalized
      seizures, apnea, and bradycardia. He was intubated and required cardiopulmonary
      resuscitation including chest compressions and medications. After stabilization
      he was transferred to the neonatal intensive care unit for further management.
      His initial laboratory tests revealed a serum calcium level of 2.4 mg/dL (normal
      range: 8.4-10.2 mg/dL) and a serum phosphorus level of 28.5 mg/dL (normal range:
      2.4-4.5 mg/dL). During the first week of admission, the infant's mother reported
      that she had administered a full pediatric Fleets enema (CB Fleet Company Inc,
      Lynchburg, VA) to him. The infant was discharged after 12 days of
      hospitalization. Anticipatory guidance on the stool patterns and behavior of
      infants can prevent misconceptions about constipation that are especially
      prevalent in new parents. Proper management of constipation, should it arise,
      should be addressed with all parents at early well-child visits to avoid
      hazardous complications of treatments. hypocalcemia, seizures, premature infants,
      enema.

PMID- 10969122
TI  - Early respiratory infections and childhood asthma.
AB  - OBJECTIVE: To assess the role of early respiratory infections in the development
      of bronchial obstruction in the first 2 years of life, and asthma by the age of 4
      years in the Oslo Birth Cohort, established in 1992-1993. Having older siblings
      and attendance to a day care center were also considered as proxy measures of
      early infections. METHODS: A total of 2531 children were followed from birth to 4
      years of age. Experiences of respiratory infections were recorded in the follow
      up surveys at 6 and 12 months of age, and children with symptoms and signs of
      bronchial obstruction during the first 2 years of life were identified and
      examined. The presence of current asthma was recorded when the children were 4
      years old. RESULTS: Children with respiratory infections during infancy had a
      higher risk of having bronchial obstruction during the first 2 years of life and
      of having asthma at 4 years of age. In logistic regression adjusting for
      confounders including other infections, the risk of asthma at 4 years of age was
      related to lower respiratory tract infection (odds ratio [OR]: 3.4; 95%
      confidence interval [CI]: 2.3-7.0), otitis media (OR: 1.8; 95% CI: 1.2-2.6),
      croup (OR: 2.1; 95% CI: 1.2-3.7) in the first year and related to the common cold
      (OR: 2.0; 95% CI: 1.3-3.1) in the first 6 months of life. The risk of current
      asthma was inversely related to older siblings after controlling for early
      respiratory infections. CONCLUSION: Early respiratory infections indicate
      increased, rather than decreased, risk of developing bronchial obstruction during
      the first 2 years of life and of having asthma at 4 years of age.

PMID- 10969123
TI  - Spinal epidural abscess in a young child.
AB  - This is a case report of a spinal epidural abscess, caused by Staphylococcus
      aureus, in a 3-year-old girl. The child presented with fever and hip pain, but
      without any neurologic deficit. After normal plain films and a normal bone scan
      were obtained, the diagnosis was made via magnetic resonance imaging (MRI). The
      neurosurgery and pediatric infectious disease teams evaluated the patient, and
      the decision was made to forego surgical drainage and to treat medically with
      appropriate intravenous and then oral antibiotics. Several months later, the
      child was doing well without any signs of neurologic sequelae. Because of the
      rarity of this disease in children, the treatment guidelines are controversial.
      Many suggest that a spinal epidural abscess must be drained surgically. Our
      experience adds to the literature a case of a child successfully treated with
      antibiotics alone. We believe that this success is related to the fact that the
      child was diagnosed by MRI early in the course of the disease and that she never
      displayed any neurologic deficits.

PMID- 10969124
TI  - Endocarditis attributable to group A beta-hemolytic streptococcus after
      uncomplicated varicella in a vaccinated child.
AB  - Varicella is generally a benign, self-limited childhood illness; however, severe,
      life-threatening complications do occur. A live, attenuated vaccine exists to
      prevent this illness, but controversy remains concerning the need to vaccinate
      children for what is generally a benign, self-limited disease, although more
      states are currently recommending this vaccine. We report a previously healthy 3
      year-old who developed varicella 6 months after vaccination with no apparent skin
      superinfections, who subsequently developed group A beta-hemolytic streptococcus
      (GABHS) bacteremia resulting in endocarditis of a normal heart valve. We are
      unaware of previous reports of endocarditis related to GABHS after varicella.
      After developing a harsh, diastolic murmur that led to an echocardiogram, aortic
      valve endocarditis was diagnosed. A 6-week course of intravenous penicillin G was
      administered. Two weeks after the initiation of therapy, the diastolic murmur was
      harsher, and echocardiography revealed a large vegetation on the posterior
      leaflet of the aortic valve, with severe aortic insufficiency and a dilated left
      ventricle. The patient subsequently developed congestive heart failure requiring
      readmission and aggressive management. One month after the initial
      echocardiogram, a repeat examination revealed worsening aortic regurgitation and
      mitral regurgitation. The patient received an additional 4 weeks of intravenous
      penicillin and gentamicin followed by aortic valve replacement using the Ross
      procedure. Our patient, the first reported case of bacteremia and endocarditis
      from GABHS after varicella, illustrates the need for the health care practitioner
      to consider both common and life-threatening complications in patients with
      varicella. While cellulitis, encephalitis, and septic arthritis may be readily
      apparent on physical examination and commonly recognized complications of
      varicella, the possibility of bacteremia without an obvious skin superinfection
      should also be entertained. The case we report is unique in that the patient had
      normal immune function, had been previously vaccinated, and developed a rare
      complication of varicella-endocarditis-in a structurally normal heart with a
      previously unreported pathogen. Although a child may have been vaccinated against
      varicella, the chance of contracting the virus still exists and parents should be
      informed of this risk. group A beta-hemolytic streptococcus, endocarditis,
      varicella, Varivax, complications of varicella.

PMID- 10969125
TI  - Unsafe sleep practices and an analysis of bedsharing among infants dying suddenly
      and unexpectedly: results of a four-year, population-based, death-scene
      investigation study of sudden infant death syndrome and related deaths.
AB  - BACKGROUND: Prone sleep and unsafe sleep surfaces increase the risk of sudden
      infant death. Recent epidemiologic studies also suggest that when an infant's
      head or face is covered by bedding, or when a sleep surface is shared with
      others, the risk of dying increases. The inference of a causal role for these
      risk factors is supported by physiologic studies and by the consistent finding
      that fewer infants die when risk factors are reduced. The prevalence of most of
      these risk factors in infant deaths in the United States is uncertain. OBJECTIVE:
      To describe the prevalence of several important risk factors related to sleep
      practices among a defined population of infants dying suddenly and unexpectedly.
      METHODS: In this population-based study, we retrospectively reviewed death-scene
      information and medical examiners' investigations of deaths in the city of St
      Louis and St Louis County between January 1, 1994 and December 31, 1997. Because
      of the potential for diagnostic overlap, all deaths involving infants <2 years
      old with the diagnoses of sudden infant death syndrome (SIDS), accidental
      suffocation, or cause undetermined were included. RESULTS: The deaths of 119
      infants were studied. Their mean age was 109.3 days (range: 6-350). The diagnoses
      were SIDS in 88 deaths, accidental suffocation in 16, and undetermined in 15.
      Infants were found prone in 61.1% of cases and were found on a sleep surface not
      designed for infants in 75.9%. The head or face was covered by bedding in 29.4%.
      A shared sleep surface was the site of death in 47.1%. Only 8.4% of deaths
      involved infants found nonprone and alone, with head and face uncovered.
      CONCLUSIONS: Using detailed death-scene descriptions, we found that similar
      unsafe sleeping practices occurred in the large majority of cases diagnosed as
      SIDS, accidental suffocation, and cause undetermined. Considering these diagnoses
      together may be useful in public health campaigns during a time when there may be
      diagnostic overlap. Regardless of the diagnosis, recommendations that infants
      sleep supine on firm sleep surfaces that lessen the risk of entrapment or head
      covering have the potential to save many lives. Campaigns are needed to heighten
      awareness of these messages and of the risks of dangerous bedsharing.

PMID- 10969126
TI  - The effect of ventilation tubes on language development in infants with otitis
      media with effusion: A randomized trial.
AB  - OBJECTIVE: To study the effectiveness of ventilation tubes on the language
      development in infants with persistent otitis media with effusion (OME). All
      existing studies addressed children 3 years of age or older. Currently, OME is
      detected and treated with ventilation tubes at a younger age. Because of the
      critical relationship between age, hearing, and language development, we
      conducted a study of the effects of ventilation tubes on language development in
      infants 1 to 2 years old with persistent OME. DESIGN: A multicenter, randomized,
      controlled trial (embedded in a cohort) with 2 treatment arms: 1) treatment with
      ventilation tubes (VT group; n = 93); or 2) with a period of watchful waiting (WW
      group; n = 94). Hearing loss and expressive and comprehensive language were
      assessed every 6 months, while tympanometry and otoscopy were performed every 3
      months. Other factors with potential influence on language development were also
      included: adenoidectomy, hospital, attending day care, sex, age at randomization,
      educational level of the mother, upper respiratory infections, and the native
      country of the parents and older siblings. The trial was designed to allow for
      the detection of a mean difference in language development of 3 months or more
      between children allocated to the VT and WW groups. RESULTS: No relevant
      differences were found in expressive or comprehensive language between the 2
      groups after adjustment for educational level of the mother, IQ of the child, and
      differences at baseline. A principal component analysis showed that in the VT
      group, the children with frequent complaints improved 1.6 months more in
      comprehensive language than those with no or some complaints. The children with
      favorable language stimulation, however, did not improve more than the children
      with less favorable stimulation. No differences were found for expressive
      language among the various clusters. The probability to improve >3 months in
      comprehensive language was.48 (95% confidence interval [CI]:.29-.68) for children
      with highly educated mothers versus.09 (95% CI:.02-.30) for children whose
      mothers had a low educational level. In the WW group, these changes were.30 (95%
      CI:.14-.53) and.14 (95% CI:.04-.35), respectively. The probability to improve >4
      months in expressive language was.52 (95% CI:.32-.71) for children with highly
      educated mothers versus.06 (95% CI:.01-.31) for children whose mothers had a low
      educational level. In the WW group these changes were.42 (95% CI:.23-.64) and.11
      (95% CI:.03-.35), respectively. In addition, there were delays in expressive
      language in both groups compared with their age expected values. The
      comprehensive language of the children who were effusion-free during the follow
      up (n = 54) improved 1.5 months (95% CI: -.2-3.2) more than that of the children
      who had persistent effusion during the entire follow-up (n = 28). No differences
      were found for expressive language development. Disregarding the intervention
      contrast, improvements in hearing seemed to be related to improvements in
      language development, especially in verbal comprehension. DISCUSSION: In this
      study, we used the Reynell, Schlichting, and Lexi tests to study the relation
      between early persistent OME and language development. These tests are directly
      related to normal language, widely accepted, and validated. It cannot be ruled
      out that more specific measures such as auditory perception tests would have
      produced more differences between groups, but the focus was on general language
      development. A total of 10 children in the WW group received treatment with
      ventilation tubes during follow-up. A further 11 children dropped out during the
      trial. A sensitivity analysis with the 10 children who received ventilation tubes
      did not change the results, and baseline differences were not found between the
      11 children who dropped out and those who completed the trial. CONCLUSIONS: In
      the total group of infants with persistent OME, ventilation tubes did not h

PMID- 10969128
TI  - A high-performance liquid chromatographic assay for reduced and oxidized
      glutathione in human erythrocytes.

PMID- 10969127
TI  - Early intervention and language development in children who are deaf and hard of
      hearing.
AB  - OBJECTIVE: The primary purpose of this study was to examine the relationship
      between age of enrollment in intervention and language outcomes at 5 years of age
      in a group of deaf and hard-of-hearing children. METHOD: Vocabulary skills at 5
      years of age were examined in a group of 112 children with hearing loss who were
      enrolled at various ages in a comprehensive intervention program. Verbal
      reasoning skills were explored in a subgroup of 80 of these children.
      Participants were evaluated using the Peabody Picture Vocabulary Test and a
      criterion-referenced measure, the Preschool Language Assessment Instrument,
      administered individually by professionals skilled in assessing children with
      hearing loss. A rating scale was developed to characterize the level of family
      involvement in the intervention program for children in the study. RESULTS: A
      statistically significant negative correlation was found between age of
      enrollment and language outcomes at 5 years of age. Children who were enrolled
      earliest (eg, by 11 months of age) demonstrated significantly better vocabulary
      and verbal reasoning skills at 5 years of age than did later-enrolled children.
      Regardless of degree of hearing loss, early-enrolled children achieved scores on
      these measures that approximated those of their hearing peers. In an attempt to
      understand the relationships among performance and factors, such as age of
      enrollment, family involvement, degree of hearing loss, and nonverbal
      intelligence, multiple regression models were applied to the data. The analyses
      revealed that only 2 of these factors explained a significant amount of the
      variance in language scores obtained at 5 years of age: family involvement and
      age of enrollment. Surprisingly, family involvement explained the most variance
      after controlling for the influence of the other factors (r =.615; F change =
      58.70), underscoring the importance of this variable. Age of enrollment also
      contributed significantly to explained variance after accounting for the other
      variables in the regression (r = -.452; F change = 19.24). Importantly, there
      were interactions between the factors of family involvement and age of enrollment
      that influenced outcomes. Early enrollment was of benefit to children across all
      levels of family involvement. However, the most successful children in this study
      were those with high levels of family involvement who were enrolled early in
      intervention services. Late-identified children whose families were described as
      limited or average in involvement scored >2 standard deviations below their
      hearing peers at 5 years of age. Even in the best of circumstances (eg, early
      enrollment paired with high levels of family involvement), the children in this
      study scored within the low average range in abstract verbal reasoning compared
      with hearing peers, reflecting qualitative language differences in these groups
      of children. CONCLUSIONS: Consistent with the findings of Yoshinaga-Itano et
      al,(1) significantly better language scores were associated with early enrollment
      in intervention. High levels of family involvement correlated with positive
      language outcomes, and, conversely, limited family involvement was associated
      with significant child language delays at 5 years of age, especially when
      enrollment in intervention was late. The results suggest that success is achieved
      when early identification is paired with early interventions that actively
      involve families.

PMID- 10969129
TI  - Fatty acid composition of LDL before and after oxidation in a diabetic population
      and influence of alpha-tocopherol concentration of LDL on their oxidability.

PMID- 10969130
TI  - Monitoring of androgenic and anti-androgenic activities by analyzing secreted
      fluid from golden hamster Harderian gland.

PMID- 10969131
TI  - Effects of dietary PUFA level and environmental temperature on fatty acid
      composition of sow milk.

PMID- 10969132
TI  - Effect of 5-hydroxytryptamine on hepatic lipid synthesis in rats in vivo.

PMID- 10969134
TI  - Age-related changes in saturated and polyunsaturated fatty acid rates in rat
      brain and hippocampus. Relationship between central nervous system fatty acid
      composition and aged-relative cognitive deficits.

PMID- 10969133
TI  - Correlation between linoleic acid intake, and linoleic acid content of adipose
      tissue and LDL lipid fractions in subjects with substantial atherosclerotic
      plaques.

PMID- 10969136
TI  - Lipid posttranslational modification of Ras oncoproteins: evidence for dual
      prenylation pathways of Ki-Ras in vivo and inhibition studies. A new strategy for
      disrupting the proliferation of Ras-related tumorigenic cells.

PMID- 10969135
TI  - Effect of ion zinc on the incorporation of

PMID- 10969138
TI  - Study of serotonin interactions with brush border membrane of rabbit jejunum
      enterocytes.
AB  - Recent studies have demonstrated that serotonin (5-hydroxytryptamine, 5-HT) may
      interact with either specific receptors or with a specific transporter that takes
      up 5-HT in the gastrointestinal tract. The purpose of the present work was to
      study the 5-HT interactions with brush border membrane from rabbit jejunum
      enterocytes. The results obtained showed that 5-HT did not seem to be transported
      by any specific system of transport in brush border membrane vesicles.
      Nevertheless, [3H]5-HT seemed to bind specifically to this membrane. The kinetic
      analysis indicated a saturable and dissociable specific binding with a
      dissociation constant K(D)=14x10(-9) M. The saturation studies with [3H]5-HT
      indicated the presence of one specific site in the brush border membrane. The
      results of displacement of [3H]5-HT specific binding from the brush border
      membrane showed that both unlabelled 5-HT and unlabelled GR113080 ([1-[(2-methyl
      sulphonyl) amino] ethyl-4-piperidinyl] methyl-1-methyl-1H-indole-3-carboxylate),
      a specific competitive antagonist of 5-HT(4) receptors, inhibited the specific
      binding of [3H]5-HT to this membrane.

PMID- 10969137
TI  - Involvement of G protein-coupled receptor kinase-6 in desensitization of CGRP
      receptors.
AB  - This investigation was undertaken to study the mechanisms of calcitonin gene
      related peptide (CGRP)-mediated desensitization using recombinant porcine CGRP
      receptors stably expressed in human embryonic kidney (HEK-293) cells.
      Pretreatment of these cells with human alphaCGRP resulted in an approximately 60%
      decrease in CGRP-stimulated adenylyl cyclase activity and an approximately 10
      fold rightward shift in the dose-response curve of CGRP. This effect was rapid
      (t(1/2) approximately 5 min) and was accompanied by a significant decrease in
      [125I]CGRP binding to membrane preparations from CGRP-pretreated cells. In
      contrast, CGRP pretreatment had no effect on isoproterenol- or forskolin
      stimulated adenylyl cyclase activity in these cells. The potential involvement of
      protein kinase A or protein kinase C in CGRP-mediated desensitization was studied
      using selective inhibitors or activators of these kinases. Pretreatment of the
      cells with forskolin (adenylyl cyclase activator) or phorbol dibutyrate (protein
      kinase C activator) had no effect on CGRP-mediated adenylyl cyclase activity and
      did not influence CGRP-mediated desensitization. However, pretreatment of the
      cells with 2-(8-[(dimethylamino)methyl]-6,7,8, 9-tetrahydropyrido[1,2-a]indol-3
      yl]-3-(1-methylindol-3-yl)m aleimide hydrochloride (Ro 32-0432) (a potent
      inhibitor of protein kinase C) resulted in significant attenuation of CGRP
      mediated desensitization with an IC(50) approximately 3 microM. To establish
      whether this effect might be due to inhibition of other protein kinases by Ro 32
      0432, its effect was tested against several G protein-coupled receptor kinases
      (GRKs). Ro 32-0432 was found to inhibit GRK2, GRK5, and GRK6 with IC(50) values
      of 29, 3.6, and 16 microM, respectively, suggesting that its effect on CGRP
      mediated desensitization might be a result of GRK inhibition. To further test
      this hypothesis, as well as the potential GRK specificity, the cells were treated
      with antisense oligonucleotides to GRK2, GRK5, and GRK6. While GRK2 and GRK5
      antisense nucleotides had no effect on CGRP-mediated desensitization, the GRK6
      antisense nucleotide treatment significantly reversed CGRP-mediated
      desensitization. These results suggest the involvement of GRK6 in CGRP-mediated
      desensitization in HEK-293 cells.

PMID- 10969139
TI  - A synthetic glycine-extended bombesin analogue interacts with the GRP/bombesin
      receptor.
AB  - alpha-amidation of a peptide (which takes place from a glycine-extended
      precursor) is required to produce biologically active amidated hormones, such as
      gastrin-releasing peptide (GRP)/Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His
      Leu-Met-NH(2) (bombesin). It was shown that glycine-extended gastrin mediates
      mitogenic effects on various cell lines by interacting with a specific receptor,
      different from the classical CCK(1) or CCK(2) receptors. On the basis of this
      observation, we have extended the concept of obtaining active glycine-extended
      forms of others amidated peptides to produce new active analogues. In this study,
      we have tested the biological behaviour of a synthetic analogue of the glycine
      extended bombesin (para-hydroxy-phenyl-propionyl-Gln-Trp-Ala-Val-Gly-His-Leu-Met
      Gly-OH or JMV-1458) on various in vitro models. We showed that compound JMV-1458
      was able to inhibit specific (3-[125I]iodotyrosyl(15)) GRP ([125I]GRP) binding in
      rat pancreatic acini and in Swiss 3T3 cells with K(i) values of approximately 10(
      8) M. In isolated rat pancreatic acini, we found that JMV-1458 induced inositol
      phosphates production and amylase secretion in a dose-dependent manner. In Swiss
      3T3 cells, the glycine-extended bombesin analogue dose-dependently produced
      [3H]thymidine incorporation. By using potent GRP/bombesin receptor antagonists,
      we showed that this synthetic glycine-extended bombesin analogue induces its
      biological activities via the classical GRP/bombesin receptor.

PMID- 10969140
TI  - Contribution of the renin-angiotensin system to subsensitivity of soluble
      guanylyl cyclase in TGR(mREN2)27 rats.
AB  - Soluble guanylyl cyclase activity and its stimulation by diethylamineNONOate was
      measured in aortae from hypertensive TGR(mREN2)27 rats (TGR) and Sprague-Dawley
      controls. Superoxide dismutase was added in vitro to evaluate the contribution of
      oxidative breakdown of nitric oxide (NO) by superoxide anions. Expression of
      soluble guanylyl cyclase was assessed by reverse transcriptase-polymerase chain
      reaction (RT-PCR). Basal and stimulated soluble guanylyl cyclase activity was
      significantly reduced in TGR rats, addition of superoxide dismutase had no
      effect. Expression of soluble guanylyl cyclase subunits was not different between
      strains. The independent contribution of hypertension and the overactive renin
      angiotensin system to soluble guanylyl cyclase subsensitivity was assessed after
      normalization of TGR's blood pressure by the Ca(2+)-channel blocker amlodipine or
      the angiotensin converting enzyme-inhibitor enalapril. Soluble guanylyl cyclase
      activity in TGR was slightly increased by amlodipine and almost completely
      restored by enalapril. In conclusion, TGR showed desensitized vascular soluble
      guanylyl cyclase, depending on their overactive renin-angiotensin system.

PMID- 10969141
TI  - Selectivity of mu-opioid receptor determined by interfacial residues near third
      extracellular loop.
AB  - We hypothesized that the selectivity profile of the rat mu-opioid receptor for
      opioid receptor-selective ligands is determined by the nature of the amino acid
      residues at highly divergent sites in the ligand-binding pocket. To determine
      which characteristics of these residues contribute to opioid receptor ligand
      selectivity, we made various mutant receptors that replaced the Lys(303) and
      Trp(318) residues near the extracellular interface of transmembrane domains VI
      and VII, respectively. Ligand binding determinations using transiently
      transfected monkey kidney epithelial (COS-1) cells show that Lys(303) mutations
      cause little change in the receptor binding profile, whereas the Trp(318) mutant
      receptors have considerably lower affinity for micro-opioid receptor-selective
      ligands and greatly increased affinity for delta-opioid receptor-selective
      ligands. The nature of these mutations show that this effect is not due to
      sterics or charge alone. [35S]guanosine-5'-O-(3-thio)-triphosphate
      ([35S]GTPgammaS) activity assays show that these residues may influence
      functional, as well as binding selection. We conclude that a primary role for
      Trp(318) is to form a basis for ligand selectivity.

PMID- 10969142
TI  - Nucleotide-evoked ion transport and [Ca(2+)](i) changes in normal and
      hyperhidrotic human sweat gland cells.
AB  - Apical and basolateral application of ATP and UTP evoked [Ca(2+)](i) and short
      circuit current (Isc) increases in normal and hyperhidrotic human eccrine sweat
      gland cells grown into functionally polarised epithelia on permeable supports.
      Basolateral application to hyperhidrotic cells exhibited a markedly greater
      increase in Isc than in normal cells. Hyperhidrotic cells also demonstrated
      differences from the normal in [Ca(2+)](i) and Isc responses to ATP when pre
      treated with thapsigargin. The data demonstrate the presence of apical and
      basolateral receptors that allow nucleotides to increase [Ca(2+)](i) and Isc. The
      results suggest that changes from the normal in transepithelial ion transport
      contribute to the characteristic excessive fluid production of hyperhidrotic
      sweat glands.

PMID- 10969143
TI  - The analgesic effects of peripheral and central administration of melatonin in
      rats.
AB  - To explore the site and mechanism of the analgesic action of melatonin, the
      present study was designed to evaluate the analgesic effects of intraperitoneal
      (i.p.) and intracerebroventricular (i.c.v. ) administration of melatonin, and to
      investigate the effect of i.c. v. naloxone on the analgesic effect induced by
      i.p. melatonin in rats. Antinociception was determined by tail-flick latency to
      hot water at 50 degrees C. On i.p. administration, melatonin (30, 60 and 120
      mg/kg) produced the antinociceptive effect in a dose-dependent manner, with an
      A(50) of 72.8 mg/kg. Administered i.c.v., melatonin (0.25, 0.5 and 1 mg/kg) also
      resulted in dose-dependent antinociception, with an A(50) of only 0.693 mg/kg.
      Injected i.c.v. to rats, 10 microg of naloxone antagonized significantly the
      antinociceptive effect induced by i.p. melatonin. It is concluded that melatonin
      has an analgesic effect in rats and the central nervous system (CNS) may be the
      primary site for melatonin to elicit the response, and the effect of melatonin is
      related to the central opioid system.

PMID- 10969144
TI  - Effects of acute and chronic tianeptine administration on serotonin outflow in
      rats: comparison with paroxetine by using in vivo microdialysis.
AB  - Using in vivo microdialysis, we compared the effects of tianeptine (an
      antidepressant drug which, in marked contrast with other antidepressants, is
      thought to increase the uptake of serotonin (5-hydroxytryptamine, 5-HT) on
      extracellular 5-HT concentrations ([5-HT](ext)) in the frontal cortex and raphe
      nuclei of freely moving rats with those of paroxetine, a potent selective
      serotonin reuptake inhibitor. A single paroxetine dose (1 mg/kg, i.p.) increased
      [5-HT](ext) over baseline in the frontal cortex and raphe nuclei, respectively. A
      single administration of tianeptine (10 mg/kg, i.p.) did not change [5-HT(ext)]
      in the two brain regions studied. Repeated exposure to paroxetine (0.5 mg/kg)
      b.i.d. for 14 days induced a sixfold significant increase in basal [5-HT](ext) in
      the raphe nuclei. Administration of tianeptine (5 mg/kg) b.i.d. for 14 days did
      not affect 5-HT baseline concentrations. In rats chronically treated with either
      paroxetine or tianeptine, drug challenge did not alter area under the curve
      values. Thus, our in vivo data indicate that tianeptine and paroxetine do not
      exert a similar in vivo effect on the serotonergic system in rat brain.

PMID- 10969145
TI  - Neurochemical changes after morphine, dizocilpine or riluzole in the ventral
      posterolateral thalamic nuclei of rats with hyperalgesia.
AB  - A number of studies suggest the involvement of glutamate in central hyperalgesia
      through NMDA receptors in animal models of inflammation. Most studies analyze
      glutamate effects at the spinal cord level. In this work, the effects of
      morphine, dizocilpine and riluzole on the hyperalgesia induced by carrageenan
      administration in the rat paw model were investigated. The effects of morphine
      and riluzole on the release of glutamate and aspartate and on the concentrations
      of citrulline and arginine in dialysates of the ventral posterolateral nucleus of
      the thalamus were also examined. All three drugs decreased hyperalgesia when
      administered prior to carrageenan injection. Morphine decreased the glutamate
      concentration in dialysates of the ventral posterolateral nucleus but did not
      affect the concentrations of the other amino acids. The effect of morphine was
      observed in the absence of painful stimulation and when pressure applied to the
      rat paw induced a nociceptive reaction. Riluzole decreased the concentrations of
      glutamate and aspartate and those of citrulline and arginine in the presence or
      absence of painful stimulation. These experiments suggest that morphine and
      riluzole attenuate the hyperalgesia induced by injection of carrageenan in the
      rat hind paw, at least partly, by decreasing glutamate release in the ventral
      posterolateral thalamic nucleus.

PMID- 10969146
TI  - Increased dopamine uptake in striatal synaptosomes after treatment of rats with
      amantadine.
AB  - The aim of the present study was to investigate the effect of short- and long
      term treatments with amantadine on the activity of the neuronal dopamine
      transporter (DAT) in the rat striatum. For this purpose, the [3H]dopamine uptake
      was measured in striatal synaptosomes prepared from rats treated for 2, 7 and 14
      days with amantadine (40 mg/kg; i.p.). After 7 days of treatment, amantadine
      increased the apparent V(max) by 30% without modification of the apparent K(m) of
      dopamine uptake whereas no change in these parameters was observed after 2 and 14
      days treatment. Binding assays conducted with [3H]GBR-12935 on membranes prepared
      from animals treated with amantadine revealed no difference in the density and
      the affinity of striatal DAT binding sites as compared to control. This indicates
      that the increased dopamine uptake was not reflecting a modification at the level
      of the DAT expression. The activity of the DAT is regulated by phosphorylation
      and one may propose that ionotropic glutamate receptors present on presynaptic
      terminals directly modulate this phosphorylation. An indirect mechanism would
      involve presynaptic dopamine receptors that control the activity of the DAT in
      response to the increased dopamine concentration in the synaptic cleft.

PMID- 10969147
TI  - Involvement of spinal protein kinase C in thermal hyperalgesia evoked by partial
      sciatic nerve ligation, but not by inflammation in the mouse.
AB  - Activation of several protein kinases contributes to the development of
      hyperalgesia evoked by injuries. The present study was designed to investigate
      the role of protein kinase C in the spinal cord in thermal hyperalgesia evoked by
      sciatic nerve ligation or by intraplantar injection of complete Freund's
      adjuvant. The paw withdrawal latency on the ipsilateral side, but not on the
      contralateral side, was markedly decreased after sciatic nerve ligation.
      Intraplantar injection of complete Freund's adjuvant also caused markedly
      decreases of the paw withdrawal latency. Intrathecal pretreatment with protein
      kinase C inhibitor calphostin C (100 and 250 ng) attenuated the decrease of the
      paw withdrawal latency evoked by sciatic nerve ligation. In contrast, the
      decrease of the paw withdrawal latency evoked by inflammation was only slightly
      attenuated by intrathecal pretreatment with calphostin C. The results indicate
      that protein kinase C in the spinal cord is involved in the development of the
      thermal hyperalgesia evoked by nerve ligation and is much less involved in the
      thermal hyperalgesia by complete Freund's adjuvant's-induced inflammation.

PMID- 10969148
TI  - A performance-dependent adjustment of the retention interval in a delayed non
      matching-to-position paradigm differentiates effects of amnestic drugs in rats.
AB  - Operant delayed non-matching-to-position (delayed non-matching-to-position) tasks
      have been widely used as tests of working memory in rats, but have suffered some
      loss in sensitivity to differentiating selective mnemonic from non-mnemonic
      deficits due to floor and ceiling effects. To circumvent this problem, a novel
      delayed non-matching-to-position was developed in which the retention interval
      was adjusted on a trial-by-trial basis to hold performance accuracy at an
      intermediate value. The present study assessed the effects of three amnestic
      drugs in this delayed non-matching-to-position. Rats were administered (i.p.)
      NMDA receptor antagonist ((5R,10S)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d,]
      cyclohepten-5,10-imine (Dizocilpine or MK-801), muscarinic receptor antagonist (
      )-scopolamine hydrobromide (scopolamine), or cannabinoid receptor agonist ((R)
      (+)-[2, 3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1, 4
      benzoxazin-6-yl]-1-naphthalenylmethanone) (WIN 55, 212-2). At high doses, both MK
      801 (0.12-0.25 mg/kg) and scopolamine (0.25 mg/kg) produced deficits not
      selective to working memory. At low doses, scopolamine (0.06-0.12 mg/kg) and MK
      801 (0.06 mg/kg) produced no deficits in any mnemonic or secondary measures. WIN
      55, 212-2 produced deficits at 2.0 mg/kg that were consistent with a specific
      impairment of working memory. Using this particular delayed non-matching-to
      position revealed that consistent changes in performance accuracy at the short
      retention interval were evident for scopolamine and MK-801, at times in the
      absence of changes in response tendency, which are consistent with an
      interpretation that these drugs produce general deficits in reference or
      procedural memory. In contrast, cannabinoid-induced deficits in choice accuracy
      support previous reports of delay-dependent deficits. Together, these data
      suggest that this delayed non-matching-to-position task is able to differentiate
      deficit patterns of amnestic drugs, and isolate the effects of motivational side
      effects of drugs from working memory measurement.

PMID- 10969149
TI  - Ethanol intake is not elevated in male 5-HT(1B) receptor knockout mice.
AB  - Recently, the phenotype of increased ethanol intake in mice lacking 5-HT(1B)
      receptors could not be replicated. We assessed ethanol consumption in male
      wildtype and 5-HT(1B) receptor knockout mice derived from the original
      population. Intake of water and ethanol (0%, 3%, 6%, 10% and 20% v/v) from two
      pipettes was determined daily for 40 days. Ethanol intake (g/kg body weight) did
      not differ between genotypes, while body weights (20-25%) and water intake (50%)
      were elevated in 5-HT(1B) receptor knockout mice. Hence, the initial finding of
      elevated ethanol intake in 5-HT(1B) receptor knockout mice may have been due to
      phenotypic differences in fluid intake.

PMID- 10969150
TI  - In vivo evidence that EMD 57033 restores myocardial responsiveness to
      intracoronary Ca(2+) in stunned myocardium.
AB  - Despite ample in vitro evidence that myofilament Ca(2+)-responsiveness of stunned
      myocardium is decreased, in vivo data are inconclusive. Conversely, while Ca(2+)
      sensitizing agents increase myofilament Ca(2+)-responsiveness in vitro, it has
      been questioned whether this also occurs in vivo. We therefore tested in open
      chest anesthetized pigs whether EMD 57033 (the (+) enantiomer of 5-[1-(3,4
      dimethoxybenzoyl)-1,2,3, 4-tetrahydro-6-quinolyl]-6-methyl-3,6-dihydro-2H-1,3, 4
      thiadiazin-2-one) increases responsiveness to Ca(2+) of non-stunned myocardium
      and restores function of stunned myocardium by normalizing the responsiveness to
      Ca(2+). Studies were performed under beta-adrenoceptor blockade to minimize the
      contribution of the phosphodiesterase-III inhibitory actions of EMD 57033.
      Consecutive intracoronary Ca(2+) infusions were used to evaluate the contractile
      response (assessed by the left ventricular end-systolic elastance, E(es)) to
      added Ca(2+) of non-stunned myocardium and myocardium stunned by 15 min coronary
      artery occlusion and 30 min reperfusion. In non-stunned propranolol-treated
      myocardium, the Ca(2+) infusions doubled E(es) (baseline 6.9+/-0.9 mmHg mm(-2),
      n=8). Following Ca(2+)-washout, subsequent EMD 57033 infusion (0.1 mg kg(-1) min(
      1), i.v.) tripled E(es) (P<0.05) and potentiated the Ca(2+)-induced increase in
      E(es) to 55.7+/-10.0 mmHg mm(-2) (P<0.05). Stunning (n=7) decreased E(es) to
      5.3+/-0.6 mmHg mm(-2) (P>0.10) and attenuated the Ca(2+)-induced increase in
      E(es) (P<0.05). Subsequent infusion of EMD 57033 increased E(es) to 6.8+/-1.8
      mmHg mm(-2) (P<0. 05) and restored responsiveness to added Ca(2+). These in vivo
      findings are consistent with the in vitro observations that myofilament Ca(2+)
      responsiveness of stunned myocardium is reduced and that EMD 57033 increases
      contractility by enhancing myofilament Ca(2+)-responsiveness.

PMID- 10969151
TI  - Novel S-nitrosothiols do not engender vascular tolerance and remain effective in
      glyceryl trinitrate-tolerant rat femoral arteries.
AB  - Organic nitrates, such as glyceryl trinitrate, are nitric oxide (NO) donor drugs
      that engender tolerance with long-term use. Here, we tested the hypothesis that
      our novel S-nitrosothiols, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy
      1,3,4,6, tetra-O-acetyl-beta-D-glucopyranose (RIG200) and S-nitroso-N-valeryl-D
      penicillamine (D-SNVP), do not induce vascular tolerance ex vivo. Femoral
      arteries from adult male Wistar rats were preconstricted with phenylephrine and
      perfused with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L
      NAME). Perfusion pressure was measured during 20-h treatment with supramaximal
      concentrations of NO donor (10 microM). Perfusion with glyceryltrinitrate caused
      a vasodilatation, which recovered over 2-20 h. In contrast, the S-nitrosothiols
      caused vasodilatations that were maintained throughout the 20-h perfusion period.
      Responses to S-nitrosothiols were partially reversed by the NO scavenger
      ferrohaemoglobin and fully reversed by the soluble guanylate cyclase inhibitor
      [1H-[1,2,4] oxadiazole [4,3-a]quinoxaline-1-one (ODQ). Glyceryltrinitrate
      tolerant vessels were fully responsive to bolus injections of S-nitrosothiols.
      Resistance to tolerance is an attractive property of our novel compounds,
      particularly in view of their sustained activity in arteries with damaged
      endothelium.

PMID- 10969152
TI  - Effects of a BLT receptor antagonist on local and remote reperfusion injuries
      after transient ischemia of the superior mesenteric artery in rats.
AB  - Reperfusion of ischemic vascular beds may lead to recruitment and activation of
      leukocytes, release of mediators of the inflammatory process and further injury
      to the affected vascular bed and to remote sites. Neutrophils appear to play a
      major role in the pathophysiology of reperfusion injury. Amongst inflammatory
      mediators shown to activate neutrophils and induce their recruitment in vivo,
      much interest has been placed on the role of leukotriene (LT)B(4). Here, we have
      assessed the effects of the BLT receptor antagonist (+)-1-(3S, 4R)-[3-(4-phenyl
      benzyl)-4-hydroxy-chroman-7-yl]-cyclopentane carboxylic acid (CP 105,696) in a
      model of neutrophil-dependent ischemia and reperfusion injury in the rat. The
      superior mesenteric artery was isolated and ischemia was induced by its total
      occlusion for 30 min. After 30 min of reperfusion, injury was assessed by
      evaluating the extravasation of Evans blue, an index of vascular permeability,
      and the levels of myeloperoxidase, an index of neutrophil accumulation, in the
      intestine, mesentery and lung. The neutrophil-dependence of the local (intestine
      and mesentery) and remote (lung) injury was confirmed by using fucoidin, a
      selectin blocker, and WT-3, an anti-CD18 monoclonal antibody. Post-ischemic
      treatment with CP 105,696 dose-dependently inhibited vascular permeability and
      neutrophil accumulation in the intestine and mesentery. CP 105,696 also blocked
      the vascular permeability changes, but not neutrophil accumulation, in the lungs
      after reperfusion injury. Virtually identical results were obtained with another
      BLT receptor antagonist, 1-(5-ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)
      heptoxy++ +)-phenyl )ethanone (LY255283). Our results suggest that post-ischemic
      treatment with BLT receptor antagonists may inhibit local and remote ischemia and
      reperfusion injury by blocking both the accumulation and/or activation of
      neutrophils.

PMID- 10969153
TI  - Temocapril, an angiotensin converting enzyme inhibitor, protects against diabetes
      induced endothelial dysfunction.
AB  - The effect of chronic treatment with the angiotensin converting enzyme inhibitor,
      temocapril, on prevention of endothelial dysfunction was evaluated in an
      experimental model of diabetes mellitus. Endothelium-dependent relaxation to
      acetylcholine was impaired while endothelium-independent relaxation to
      nitroglycerin was unaltered in diabetic aortic ring segments. Treatment of
      diabetic animals with temocapril prevented the impaired endothelium-dependent
      relaxation without altering responses to nitroglycerin. Acetylcholine-induced
      relaxation was largely due to nitric oxide (NO)-mediated relaxation; however, a
      small but significant portion of relaxation in aortic rings from temocapril
      treated diabetic rats was resistant to inhibition by the nitric oxide synthase
      (NOS) inhibitor, L-nitroarginine.

PMID- 10969154
TI  - Partial agonist activity of carteolol on atypical beta-adrenoceptors in the
      guinea pig duodenum.
AB  - The partial agonist activities of carteolol were investigated on atypical beta
      adrenoceptors of duodenum on the guinea pig. Carteolol produced a concentration
      dependent relaxation of the guinea pig duodenum (pD(2)=4.85), which was not
      significantly affected by propranolol (1 microM). In the presence of propranolol
      (1 microM), however, the non-selective beta(1)-, beta(2)- and beta(3)
      adrenoceptor antagonist, bupranolol (30 microM), caused a rightward shift of the
      concentration-response curves for carteolol (apparent pA(2)=5.31). Moreover,
      carteolol (10 microM) weakly, but significantly, antagonized the relaxations in
      response to catecholamines (isoprenaline, noradrenaline and adrenaline), to a
      selective beta(3)-adrenoceptor agonist, (R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)
      2-hydroxyethyl)amino]propyl]pheno xyacetic acid sodium salt (BRL37344), and to a
      non-conventional partial beta(3)-adrenoceptor agonist, [4-[3-[(1, 1
      dimethylethyl)amino]-2-hydroxypropoxy]-1, 3-dihydro-2H-benzimidazol-2-one]
      hydrochloride (CGP12177A), also in the guinea pig duodenum (apparent pA(2)=5.77,
      5.92, 6.05, 6.56 and 5. 58, respectively). These results suggest that the partial
      agonist effects of carteolol are mediated by atypical beta-adrenoceptors in the
      guinea pig duodenum.

PMID- 10969155
TI  - The contractile effects of endothelins on the smooth muscle of the rat prostate
      gland.
AB  - Endothelin-1 elicited tonic contractions of rat prostatic smooth muscle that were
      unaffected by prazosin (0.5 microM), tetrodotoxin (1 microM) or guanethidine (10
      microM). The rank order of potency of the endothelin isopeptides was endothelin
      1>endothelin-2> or =endothelin-3. Sarafotoxin S6B was approximately equipotent
      with endothelin-1 in eliciting tonic contractions, but neither of the selective
      endothelin ET(B) receptor-agonists, sarafotoxin S6C (0.1 nM-0.3 microM) and
      BQ3020 (Ac-[Ala (11,15)]endothelin-1(6-21); 0.1 nM-0.3 microM), affected
      prostatic smooth muscle tone. The selective endothelin ET(A) receptor antagonist,
      BQ123 (cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp; 1 microM), attenuated responses to
      endothelin-1, -2 and -3, while the non-selective endothelin receptor antagonist
      bosentan (1 microM) and the selective endothelin ET(B) receptor antagonist BQ788,
      (Dmpc-gamma-MeLeu(9)-D-Trp(l-CO(2)CH(3))-D-Nle-OH; 1 microM) attenuated responses
      to endothelin-3 only. Contractions induced by exogenous administration of
      noradrenaline were unaffected by preincubation of tissues in BQ123 (1 microM)
      indicating the selectivity of this antagonist. These data suggest that
      endothelins mediate contractions of the rat prostate by action at endothelin
      ET(A) receptors.

PMID- 10969156
TI  - Characterization of beta-adrenoceptor subtypes in the ferret urinary bladder in
      vitro and in vivo.
AB  - In the present study, the beta-adrenoceptor subtypes distributed in the detrusor
      of the ferret were investigated in functional experiments in vitro and in vivo
      using a variety of beta-adrenoceptor agonists and antagonists. All the beta
      adrenoceptor agonists tested relaxed the isolated detrusor strip, the rank order
      of potency being (+/-)-(R*, R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]
      amino]propyl]phenoxy]- acetic acid sodium (BRL 37344A)>(+/-)-4-(3-t-butylamino-2
      hydroxypropoxy) benzimidazol-2-one (CGP-12177A), isoprenaline and (R, R)-5-[2-[[2
      (3-chlorophenyl)-2-hydroxyethylamino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate
      (CL 316,243)>dobutamine and procaterol. In antagonist experiment, 3-(2
      allylphenoxy)-1-[(1S)-1,2, 3,4-tetrahydro-naphth-1-ylamino]-(2S)-2-propanol
      hydrochloride (SR 58894A), but neither 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl
      4-trifluoromethyl)1H-imidaz ole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide
      monomethane sulphonate (CGP-20712A) nor erythro-(+/-)-1-(7-methylindan-4-yloxy)-3
      isopropylaminob utan-2-ol hydrochloride (ICI-118,551), caused a rightward shift
      of the concentration-relaxation curve for isoprenaline. In in vivo experiments,
      isoprenaline and CL 316,243 each reduced bladder pressure in a dose-dependent
      manner. CL 316,243 was the only drug that did not produce any significant
      influences on blood pressure and heart rate at doses that reduced bladder
      pressure. The present functional study provides the first evidence that
      relaxation of the ferret detrusor by beta-adrenoceptor activation is mediated
      mainly via the beta(3)-adrenoceptor, as in the human detrusor.

PMID- 10969157
TI  - Effect of dimethylthiourea, a hydroxyl radical scavenger, on cigarette smoke
      induced bronchoconstriction in guinea pigs.
AB  - Cigarette smoke exposure causes bronchoconstriction in guinea pigs by stimulating
      cholinergic and excitatory nonadrenergic, noncholinergic (eNANC)-nerves in vagus
      system. The aim of this study is to elucidate the role of hydroxyl radical (OH(
      )), contained in cigarette smoke, in bronchoconstriction. Anaesthetized animals
      were exposed to 80 puffs of smoke for 4 min. Pretreatment with dimethylthiourea,
      a OH(-) scavenger, significantly inhibited cigarette smoke-induced
      bronchoconstriction. To investigate its site of action, effects of
      dimethylthiourea were examined on vagally mediated bronchcoconstriction by
      electrical stimulation and on the bronchoconstriction by intravenous
      acetylcholine and neurokinin-A. Dimethylthiourea did not inhibit
      bronchoconstriction evoked by vagal stimulation, acetylcholine or neurokinin-A.
      These results suggest that dimethylthiourea inhibits cigarette smoke-induced
      bronchoconstriction by scavenging the smoke-derived OH(-), but not by inhibiting
      airway nerve function.

PMID- 10969158
TI  - Effects of repeated administration of baclofen on transient lower esophageal
      sphincter relaxation in the dog.
AB  - The metabotropic gamma-aminobutyric acid (GABA) receptor (GABA(B) receptor)
      agonist baclofen inhibits transient lower esophageal sphincter relaxation in
      dogs, ferrets, and humans. Since transient lower esophageal sphincter relaxations
      are the major cause of gastroesophageal reflux, GABA(B) receptor agonists may
      have a therapeutic value in the treatment of gastroesophageal reflux disease.
      However, repeated stimulation of the GABA(B) receptor may induce receptor
      desensitization which, depending on the magnitude, would limit the therapeutic
      effect. The aim of the present study was to follow the effects of baclofen on
      transient lower esophageal sphincter relaxation in the dog after repeated
      administration. The effect of 7 micromol/kg baclofen b.i.d. (given
      intragastrically) on transient lower esophageal sphincter relaxation and related
      parameters was determined in four dogs. Transient lower esophageal sphincter
      relaxations stimulated by infusion of liquid nutrient and insufflation of air
      were quantified after placebo and then after the 1st, 13th, and 27th dose.
      Baclofen reduced the number of transient lower esophageal sphincter relaxations
      without affecting their duration, and the latency to the first transient lower
      esophageal sphincter relaxation was prolonged. Basal sphincter pressure was
      unaffected by baclofen, and the number of reflux episodes and esophageal acid
      exposure decreased. There was a statistically insignificant numerical decrease
      (approximately 30%) in the effect of baclofen on transient lower esophageal
      sphincter relaxation after the seventh dose but this was not further accentuated
      after the 27th dose. The effect on latency was also reduced with repeated dosing,
      but again, the effects after the 1st, 13th, and 27th doses were not statistically
      significant. The attenuation of acid exposure and reflux episodes was unaltered
      after repeated dosing. Three of the dogs greatly reduced their food intake within
      the first 2-3 days but this side effect was resolved subsequently. It is
      concluded that repeated dosing of baclofen leads to mild tolerance development in
      terms of the effects on transient lower esophageal sphincter relaxation, but that
      the tolerance is much less pronounced than that previously reported in other
      animal models.

PMID- 10969160
TI  - Margaret Barnes - An appreciation.

PMID- 10969159
TI  - Effect of combined leukotriene D(4) and thromboxane A(2) receptor antagonist on
      mediator-controlled resistance in guinea pigs.
AB  - The effects of YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4
      chlorobenzenesu lfonyl )propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide
      monosodium salt monohydrate), a new dual antagonist for leukotriene D(4) and
      thromboxane A(2) receptors, on antigen-induced increases in airway resistance
      were investigated in mediator-controlled novel asthmatic models using actively
      sensitized guinea pigs. While the predominant mediator was thromboxane A(2),
      complete inhibition of cyclooxygenase induced mediation by cysteinyl
      leukotrienes. About 1-mg/kg indomethacin induced a state where both mediators
      participated equally. YM158 inhibited increases in resistance whether only one or
      both mediators were involved. When leukotriene D(4) and thromboxane A(2) equally
      participated, ED(50) values for 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2
      (tetrazol-5-yl)-4 H-1-benzo pyran hemihydrate (pranlukast; 3.9 mg/kg) and 7
      (3,5,6-trimethyl-1, 4-benzoquinon-2-yl)-7-phenylheptanoic acid (seratrodast; 2.1
      mg/kg) were similar to that for YM158 (8.3 mg/kg), although those effects on the
      corresponding mediator-induced reaction were 10 times stronger than those of
      YM158. Additionally, the maximum inhibition of YM158 was stronger than those of
      either single receptor antagonist. In conclusion, YM158 has a potentially greater
      efficacy in wider types of experimental asthmatic models than single receptor
      antagonists.

PMID- 10969161
TI  - Roles of experimental marine ecology in coastal management and conservation.
AB  - The paper reviews the main findings of rocky shore and subtidal nearshore
      experimental marine ecology (EME) in cold and temperate marine ecosystems during
      the past four decades. It analyzes the role of EME in coastal management and
      conservation. The historical development of strategies for managing single or
      multispecies fisheries are reviewed. The published results show over-exploitation
      and depletion of more than 60% of the fish stocks and a lack of connection
      between the management of fisheries and results derived from experimental marine
      ecology. This is mainly due to: (a) the different temporal and spatial scale at
      which most marine ecologists and fishery managers operate; (b) the lack of long
      term fishery monitoring and adaptive techniques for management; and (c)
      limitations in the design of experiments on fisheries. Large-scale oceanic
      perturbations, due to combinations of excessive resource exploitation and
      environmental variability coupled with present trends in management approaches
      are discussed. Modern approaches and tools for management of fisheries, such as
      Adaptive Management (AM), Territorial User Rights in Fisheries (TURFs),
      Individual Transferrable Quotas and Non-Transferrable Quotas (ITQs, INTQs) are
      discussed in the context of small-scale fisheries and EME. Published views on
      limits of applied ecological research with regards to management of fisheries are
      discussed. Linkages between EME, marine conservation and the establishment of
      Marine Protected Areas (MPAs) and experimental exclusions of humans are
      highlighted. Results derived from MPAs, such as: (a) species or community trophic
      cascades, and (b) the role of key-stone species and species interaction
      strengths, are discussed. It is concluded that the role of EME in conservation
      has been greater than has been the case in management of fisheries. The potential
      to link EME, conservation and the management of fisheries is exemplified through
      the proposed establishment in Chile of a connected network of Scientific
      Reserves, MPAs and TURFs sites. The final conclusion is that to cross-fertilize
      EME, conservation and management, there are three main challenges: (1) to end the
      traditional view of approaching the management of fisheries and marine
      conservation as contradictory/antagonizing issues; (2) to improve communications
      between experimental marine ecology and the management of fisheries through the
      implementation of experimentation and adaptive management; (3) to improve
      linkages between marine conservation, the management of fisheries and social
      sciences.

PMID- 10969162
TI  - The measurement of marine species diversity, with an application to the benthic
      fauna of the Norwegian continental shelf.
AB  - Species diversity includes two aspects, the number of species (species richness)
      and the proportional abundances of the species (heterogeneity diversity). Species
      richness and heterogeneity diversity can be measured over different scales; a
      single point, samples, large scales, biogeographical provinces and in assemblages
      and habitats. In the literature, the terminology of these scales is confused.
      Here, scales are given a uniform notation. Scales of species richness and
      heterogeneity diversity are distinguished from turnover (beta) diversity, which
      is the degree of change in species composition along a gradient. Methods of
      measurement of the scales of species richness, heterogeneity diversity, turnover
      diversity and for estimating total species richness are reviewed. Two methods for
      measuring heterogeneity diversity are recommended Exp H' (where H' is the Shannon
      Wiener index) and 1/Simpson's index, together with an equitability index J'. The
      reviewed methods are then applied to a data set from the Norwegian continental
      shelf to illustrate the advantages of the recommended methods. Finally, the
      application of the methods to assessment of effects of disturbance, to studies of
      gradients of species richness and to conservation issues are discussed.

PMID- 10969163
TI  - Experimental ecology of rocky intertidal habitats: what are we learning?
AB  - Experimental analyses of causes of patterns of distribution and abundance of
      intertidal animals and plants on rocky shores have been a major activity for many
      years. In this review, some of the themes and topics that have emerged from such
      analyses are briefly discussed to provide an up-date for practitioners and
      ecologists working in other habitats. Conceptual issues include the widespread
      occurrence of transphyletic use of the same resources (space and food), theories
      and experimental analyses of intermediate disturbance in relation to numbers of
      species, the complex but pervasive nature of indirect interactions among species,
      relative importance of 'top-down' versus 'bottom-up' control of assemblages and
      the importance to rocky intertidal species of 'supply-side' influences on
      densities and interactions. Methodological advances include experimental designs
      for complex and patchy, interacting sets of species, the importance of controls
      in experimental manipulations and methods for analyses of hierarchical scales of
      patterns and processes. Finally, some contributions to social issues (pollution,
      biodiversity) and some scenarios for future directions are briefly considered.

PMID- 10969164
TI  - Poor design of behavioural experiments gets poor results: examples from
      intertidal habitats.
AB  - Many patterns of distribution and abundance of intertidal animals are explained
      by processes of movements of animals, selecting particular habitats or levels on
      the shore, or interacting with other species. Movements of intertidal animals
      have therefore been studied over many years. During this long history, much
      intertidal ecology has changed in focus from broad-scale to small-scale patterns
      and processes, although there has been recent refocus on a combination of many
      scales. Simultaneously, there has been an increase in the incidence of field
      experiments and growing recognition that behaviour is more flexible than
      originally thought. This review examines changes in the ways that experiments on
      movements on intertidal animals have been and are being done, taking into account
      these changes in emphasis. Although some progress has been made, there is still a
      long way to go. The idea is still prevalent that behaviour is simple, rather
      invariant and that the animals respond to broad-scale cues that have
      traditionally been of interest to many investigators. This means that many
      experiments are still designed to minimise (or ignore) natural variation in
      behaviour rather than to measure it and that any associated disturbances are
      considered irrelevant and therefore not evaluated. Understanding the role that
      behaviour has in establishing and maintaining many of the patterns observed on
      intertidal shores is crucial to our understanding of the ecology of these
      habitats. Better experiments, designed logically with appropriate controls to
      evaluate realistic processes and to measure how behaviour varies among places and
      from time to time can only improve this understanding.

PMID- 10969165
TI  - Observations in ecology: you can't make progress on processes without
      understanding the patterns.
AB  - Coastal marine ecology is, quite properly, increasingly focussed on experimental
      tests of hypotheses about processes. These are, however, done to explain
      observations and patterns. It is therefore appropriate to be able to publish
      quantitative observations to provide the context and basis for studying
      mechanisms and processes. Ecologists are concerned about very different types of
      observations. Some areas of study are still totally dependent on observational,
      descriptive evidence; some depend on mensurative tests of hypotheses about
      patterns. Tests of hypotheses about patterns are also needed to validate casual
      or qualitative observations. Guide-lines for what constitutes appropriate or
      publishable ecological descriptions are discussed here. These recognize the
      experimental, hypothesis-testing nature of many descriptive studies and consider
      the relevance of sound logic and experimental design in the planning, collection
      and interpretation of observations.

PMID- 10969166
TI  - Marine biodiversity and ecosystem services: an elusive link.
AB  - Efforts to test the hypothesised positive link between ecosystem services and
      functions and biodiversity are increasing in order to forecast the consequences
      of the present erosion of biodiversity on ecosystem functions and to provide an
      additional basis for the conservation of biodiversity. These efforts have been,
      however, modest in marine ecosystems. An examination of seagrass communities,
      which are simple assemblages with a limited membership of about 50 species
      worldwide and <12 species in any one community, provides, however, strong
      evidence for the existence of such positive link between species richness and
      ecosystem functions. Ecosystem functions are, however, dependent on the
      particular membership of the community, rather that its number, for the functions
      are species-specific properties. Yet evidence, is provided, that an increasing
      species richness should be, on average, linked to an increase in the functional
      repertoire present in the community, will lead to a more efficient use of
      resources and a greater capacity to ensure the sustainability of ecosystem
      functions under disturbance or ecosystem change. Closer examination indicates
      that the functional variability of mixed-species seagrass assemblages is
      correlated to the variability in species size, whereas species of similar size
      tend to show similar functional capacities and, therefore, a greater degree of
      functional redundancy. In addition, the demonstration of positive interactions in
      seagrass communities, which are also dependent on the presence of engineering
      species in the community that facilitate the growth of other species, provides
      increasing grounds to expect an enhanced functional performance of mixed
      communities over that expected from a simple additive contribution of the
      community members. Multispecific communities also hold, within the functional
      repertoire they contain, many unrealised functional potentials that may prove
      instrumental to ensure the sustainability of ecosystem functions in the presence
      of disturbance or a changing environment. The arguments offered, illustrated for
      the comparatively simple seagrass communities, provide strong reasons to expect a
      strong - if difficult to test experimentally - positive relationship between
      species diversity and the functions of marine ecosystems and, thereby, the
      services they yield to humanity.

PMID- 10969167
TI  - Review of nitrogen and phosphorus metabolism in seagrasses.
AB  - Within the past few decades, major losses of seagrass habitats in coastal waters
      impacted by cultural eutrophication have been documented worldwide. In
      confronting a pressing need to improve the management and protection of seagrass
      meadows, surprisingly little is known about the basic nutritional physiology of
      these critical habitat species, or the physiological mechanisms that control
      their responses to N and P gradients. The limited available evidence to date
      already has revealed, for some seagrass species such as the north temperate
      dominant Zostera marina, unusual responses to nutrient enrichment in comparison
      to other vascular plants. Seagrasses derive N and P from sediment pore water
      (especially ammonium) and the water column (most nitrate). The importance of
      leaves versus roots in nutrient acquisition depends, in part, on the enrichment
      conditions. For example, a shift from reliance on sediment pore water to
      increased reliance on the overlying water for N and P supplies has been observed
      under progressive water-column nutrient enrichment. Seagrasses may be N-limited
      in nutrient-poor waters with sandy or (less so) organic sediments, and P-limited
      in carbonate sediments. On the basis of data from few species, seagrasses appear
      to have active uptake systems for NO(3)(-) and PO(4)(-3), but NH(4)(+) uptake may
      involve both low- and high-affinity systems. P(i) uptake affinities reported thus
      far are much lower than values for active ammonium uptake, but comparable to
      values for nitrate uptake by leaf tissues. Beyond such basic information,
      seagrass species have shown considerable variation in nutritional response.
      Dominance of acropetal versus basipetal nutrient translocation appears to vary
      among species as an innate trait. While some species follow classic Michaelis
      Menten kinetics for N(i) uptake, others have exhibited sustained linear uptake
      with limited or negligible product feedback inhibition, perhaps in adaptation to
      oligotrophic environments. Zostera marina also is able to maintain nitrate
      reductase (NR) activity during dark periods if adequate carbohydrate reserves and
      substrate are available. Thus, this species can respond to nitrate pulses
      throughout a diel cycle, rather than being limited as most plants to nitrate
      uptake during the light period. Further adaptations may have occurred for
      seagrasses in extremely nitrate-depauperate conditions. For example, Halophila
      decipiens and H. stipulacea lack inducible NR and apparently have lost the
      ability to reduce nitrate; and a biphasic rather than hyperbolic P(i) uptake
      curve, with 'surge' uptake, has been described for Zostera noltii. Many
      seagrasses respond favorably to low or moderate N and/or P enrichment. However,
      excessive N(i) loading to the water column can inhibit seagrass growth and
      survival, not only as an indirect effect by stimulating algal overgrowth and
      associated light reduction, but-for some species-as a direct physiological
      effect. The latter direct impact has been most pronounced for plants growing in
      sandy (nutrient-poor) sediments, and is exacerbated by elevated temperatures
      and/or light reduction. Ammonia toxicity, known for many vascular plants, has
      been reported in seagrasses Ruppia drepanensis and Z. marina (125 uM water-column
      NH(4)(+), 5 weeks). Z. marina has shown to be inhibited, as well, by pulsed water
      column nitrate enrichment (as low as 3.5-7 uM NO(3)(-), 3-5 weeks), which is
      actively taken up without apparent product feedback inhibition. Inhibition by
      elevated nitrate has also been reported, with description of the underlying
      physiological mechanisms, in certain macroalgae and microalgae. In Z. marina,
      this effect has been related to the high, sustained energy demands of nitrate
      uptake, and to inducement of internal carbon limitation by the concomitant
      'carbon drain' into amino acid assimilation. In contrast, nitrate enrichment can
      stimulate growth of Z. marina when the sediment, rather than the water column, is
      the source. Because seagrass species have shown considerable variation in
      nutritional response, inferences about one well-studied species, from one
      geographic location, should not be applied a priori to that species in other
      regions or to seagrasses in general. Most of the available information has been
      obtained from study of a few species, and the basic nutritional physiology of
      many seagrasses remains to be examined and compared across geographic regions.
      Nonetheless, the relatively recent gains in general understanding about the
      physiological responses of some seagrass species to nutrient gradients already
      have proven valuable in both basic and applied research. For example,
      physiological variables such as tissue C:N:P content have begun to be developed
      as integrative indicators of nutrient conditions and anthropogenic nutrient
      enrichment. To strengthen insights for management strategies to optimize seagrass
      survival in coastal waters adjacent to exponential human population growth and
      associated nutrient inputs, additional emphasis is critically needed to assess
      the role of variable interactions-among inorganic as well as organic N, P and C,
      environmental factors such as temperature, light, and other community components
      in controlling the physiology, growth and survival of these ecologically
      important marine angiosperms.

PMID- 10969168
TI  - Overview of the physiological ecology of carbon metabolism in seagrasses.
AB  - The small but diverse group of angiosperms known as seagrasses form submersed
      meadow communities that are among the most productive on earth. Seagrasses are
      frequently light-limited and, despite access to carbon-rich seawaters, they may
      also sustain periodic internal carbon limitation. They have been regarded as C3
      plants, but many species appear to be C3-C4 intermediates and/or have various
      carbon-concentrating mechanisms to aid the Rubisco enzyme in carbon acquisition.
      Photorespiration can occur as a C loss process that may protect photosynthetic
      electron transport during periods of low CO(2) availability and high light
      intensity. Seagrasses can also become photoinhibited in high light
      (generally>1000 uE m(-2) s(-1)) as a protective mechanism that allows excessive
      light energy to be dissipated as heat. Many photosynthesis-irradiance curves have
      been developed to assess light levels needed for seagrass growth. However, most
      available data (e.g. compensation irradiance I(c)) do not account for belowground
      tissue respiration and, thus, are of limited use in assessing the whole-plant
      carbon balance across light gradients. Caution is recommended in use of I(k)
      (saturating irradiance for photosynthesis), since seagrass photosynthesis
      commonly increases under higher light intensities than I(k); and in estimating
      seagrass productivity from H(sat) (duration of daily light period when light
      equals or exceeds I(k)) which varies considerably among species and sites, and
      which fails to account for light-limited photosynthesis at light levels less than
      I(k). The dominant storage carbohydrate in seagrasses is sucrose (primarily
      stored in rhizomes), which generally forms more than 90% of the total soluble
      carbohydrate pool. Seagrasses with high I(c) levels (suggesting lower efficiency
      in C acquisition) have relatively low levels of leaf carbohydrates. Sucrose-P
      synthase (SPS, involved in sucrose synthesis) activity increases with leaf age,
      consistent with leaf maturation from carbon sink to source. Unlike terrestrial
      plants, SPS apparently is not light-activated, and is positively influenced by
      increasing temperature and salinity. This response may indicate an osmotic
      adjustment in marine angiosperms, analogous to increased SPS activity as a
      cryoprotectant response in terrestrial non-halophytic plants. Sucrose synthase
      (SS, involved in sucrose metabolism and degradation in sink tissues) of both
      above- and belowground tissues decreases with tissue age. In belowground tissues,
      SS activity increases under low oxygen availability and with increasing
      temperatures, likely indicating increased metabolic carbohydrate demand.
      Respiration in seagrasses is primarily influenced by temperature and, in
      belowground tissues, by oxygen availability. Aboveground tissues (involved in C
      assimilation and other energy-costly processes) generally have higher respiration
      rates than belowground (mostly storage) tissues. Respiration rates increase with
      increasing temperature (in excess of 40 degrees C) and increasing water-column
      nitrate enrichment (Z. marina), which may help to supply the energy and carbon
      needed to assimilate and reduce nitrate. Seagrasses translocate oxygen from
      photosynthesizing leaves to belowground tissues for aerobic respiration. During
      darkness or extended periods of low light, belowground tissues can sustain
      extended anerobiosis. Documented alternate fermentation pathways have yielded
      high alanine, a metabolic 'strategy' that would depress production of the more
      toxic product ethanol, while conserving carbon skeletons and assimilated
      nitrogen. In comparison to the wealth of information available for terrestrial
      plants, little is known about the physiological ecology of seagrasses in carbon
      acquisition and metabolism. Many aspects of their carbon metabolism - controls by
      interactive environmental factors; and the role of carbon metabolism in salt
      tolerance, growth under resource-limited conditions, and survival through periods
      of dormancy - remain to be resolved as directions in future research. Such
      research will strengthen the understanding needed to improve management and
      protection of these environmentally important marine angiosperms.

PMID- 10969169
TI  - Paradigm lost: reconsidering functional form and group hypotheses in marine
      ecology.
AB  - Although functional form and functional group models for marine algae have been
      used extensively, there is little general literature support for these models,
      and many studies have shown that associated hypotheses are often incorrect. In
      functional form/group models, a wide range of ecological and physiological
      functions are assumed to be correlated with general algal form or morphology. In
      contrast, functional group approaches have been used most successfully in
      terrestrial and aquatic systems when groupings are based on a particular function
      rather than overall plant morphology, and when addressing ecosystem-level
      questions. In this type of functional group approach, a given set of species
      would likely be grouped differently depending on the function under
      consideration. Functional groupings are appropriate for many situations and
      questions, but not all. Certainly, grouping taxa by a particular function can be
      very useful and often necessary for many ecosystem-level questions and modeling,
      especially where qualitative results are more important than quantitative
      predictions, and when there are too many species in a system to consider them all
      individually. However, when one considers species-species interactions or
      questions about population biology, the specific responses of individual species
      must be considered. To make functional group models more useful, we recommend
      that groupings be based on specific functions (e.g. nutrient uptake rates,
      photosynthesis rates, herbivore resistance, disturbance resistance, etc.) rather
      than gross morphology. Explicit testing of performance of a particular function
      should be made before generalizations can be assumed, and groupings should be
      used for questions/approaches where they are most appropriate. If models fail
      when tested, they should be modified using the additional information to generate
      new hypotheses and models, and then retested.

PMID- 10969170
TI  - Trends in research on shallow water food webs.
AB  - Making sense of the spider-web networks of interactions between species in food
      webs has been a major pre-occupation of ecologists over the last 60 years. This
      review describes the early attempts to reduce this complexity through the
      grouping of individual taxa into functional categories (such as trophic levels),
      through adopting the energy flow or systems approach as epitomised by the
      International Biological Programme, and most recently by the derivation of web
      statistics by food web theorists. The strengths and weaknesses of these
      approaches are discussed in relation to empirical field experiments for
      unravelling the processes responsible for organising communities and an
      assessment made of the representation of these approaches in the marine
      biological literature.

PMID- 10969171
TI  - Estimation of phytoplankton production from space: current status and future
      potential of satellite remote sensing.
AB  - A new generation of ocean colour satellites is now operational, with frequent
      observation of the global ocean. This paper reviews the potential to estimate
      marine primary production from satellite images. The procedures involved in
      retrieving estimates of phytoplankton biomass, as pigment concentrations, are
      discussed. Algorithms are applied to SeaWiFS ocean colour data to indicate
      seasonal variations in phytoplankton biomass in the Celtic Sea, on the
      continental shelf to the south west of the UK. Algorithms to estimate primary
      production rates from chlorophyll concentration are compared and the advantages
      and disadvantage discussed. The simplest algorithms utilise correlations between
      chlorophyll concentration and production rate and one equation is used to
      estimate daily primary production rates for the western English Channel and
      Celtic Sea; these estimates compare favourably with published values. Primary
      production for the central Celtic Sea in the period April to September inclusive
      is estimated from SeaWiFS data to be 102 gC m(-2) in 1998 and 93 gC m(-2) in
      1999; published estimates, based on in situ incubations, are ca. 80 gC m(-2). The
      satellite data demonstrate large variations in primary production between 1998
      and 1999, with a significant increase in late summer in 1998 which did not occur
      in 1999. Errors are quantified for the estimation of primary production from
      simple algorithms based on satellite-derived chlorophyll concentration. These
      data show the potential to obtain better estimates of marine primary production
      than are possible with ship-based methods, with the ability to detect short-lived
      phytoplankton blooms. In addition, the potential to estimate new production from
      satellite data is discussed.

PMID- 10969172
TI  - Top-down and bottom-up community regulation in marine rocky intertidal habitats.
AB  - Strong top-down control by consumers has been demonstrated in rocky intertidal
      communities around the world. In contrast, the role of bottom-up effects
      (nutrients and productivity), known to have important influences in terrestrial
      and particularly freshwater ecosystems, is poorly known in marine hard-bottom
      communities. Recent studies in South Africa, New England, Oregon and New Zealand
      suggest that bottom-up processes can have important effects on rocky intertidal
      community structure. A significant aspect of all of these studies was the
      incorporation of processes varying on larger spatial scales than previously
      considered (10's to 1000's of km). In all four regions, variation in
      oceanographic factors (currents, upwelling, nutrients, rates of particle flux)
      was associated with different magnitudes of algal and/or phytoplankton abundance,
      availability of particulate food, and rates of recruitment. These processes led
      to differences in prey abundance and growth, secondary production, consumer
      growth, and consumer impact on prey resources. Oceanographic conditions therefore
      may vary on scales that generate ecologically significant variability in
      populations at the bottom of the food chain, and through upward-flowing food
      chain effects, lead to variation in top-down trophic effects. I conclude that top
      down and bottom-up processes can be important joint determinants of community
      structure in rocky intertidal habitats, and predict that such effects will occur
      generally wherever oceanographic 'discontinuities' lie adjacent to rocky
      coastlines. I further argue that increased attention by researchers and of
      funding agencies to such benthic-pelagic coupling would dramatically enhance our
      understanding of the dynamics of marine ecosystems.

PMID- 10969173
TI  - Communication of the central nervous and the immune systems.

PMID- 10969174
TI  - Cytokines and immunity in multiple sclerosis: the dual signal hypothesis.
AB  - Multiple sclerosis (MS) is considered an immune-mediated disease of the central
      nervous system (CNS) sustained by a chronic inflammatory process leading to
      patchy demyelination and axonal loss. However, the inflammatory triggering event
      as well as the target of the pathogenic process in MS are still partially
      unknown. We report evidence that a 'local' inflammatory process occurring in the
      CNS (considered as a reaction of blood vessels in vascularized living tissue to a
      local injury leading to the accumulation of fluid and blood cells) along with a
      concomitant, but possibly unrelated, peripheral inflammatory event may trigger a
      CNS-specific autoimmune reaction cascade sustaining the MS pathogenesis. In the
      CNS, inflammatory mediators (mainly cytokines) act either as regulatory (i.e.
      activation of glial cells, shaping the autoimmune response) or effector molecules
      (i.e. myelinotoxicity, oligodendrotoxicity). In the periphery, inflammatory
      cytokines induce, in a bystander fashion, activation of monocytes and T cells.
      Among this latter cell population there are myelin-specific T cells belonging to
      the normal 'autoimmune' repertoire that home to the CNS where they may trigger
      the continuous recruitment of effector cells (macrophages) from the periphery.
      The concept that two concomitant, but possibly unrelated, inflammatory events,
      occurring in the CNS and in the periphery, represent the crucial elements
      sustaining MS, might reveal a more comprehensive view (dual signal hypothesis) of
      the entire etiopathogenic process underlying this disease.

PMID- 10969175
TI  - Cytokines and hormones as possible links between endocrinosenescence and
      immunosenescence.
AB  - Deterioration of the immune system and the endocrine system during aging is
      thought to contribute to increased morbidity and mortality. Since bidirectional
      interrelations of both systems are present in the young and in the elderly,
      endocrinosenescence modulates the immune system and immunosenescence changes the
      endocrine system. This review focuses on age-related changes of the two systems
      and provides examples for the interaction of both systems during aging. It is
      demonstrated that both systems modulate each other in a probably unfavorable way
      which may be a cofactor in the aging process. Understanding of these
      bidirectional physiological mechanisms will help to define targets for
      therapeutical intervention to improve the health of aging people.

PMID- 10969176
TI  - Mechanisms of anti-inflammatory action and of immunosuppression by
      glucocorticoids: negative interference of activated glucocorticoid receptor with
      transcription factors.
AB  - Glucocorticoids are the most widely used anti-inflammatory and immunomodulatory
      agents, whose mechanism of action is based mainly on interference with the
      activity of transcription factors, such as nuclear factor kappaB (NF-kappaB) and
      activator protein-1 (AP-1). The precise molecular mechanisms of gene repression
      by glucocorticoids are a controversial matter, due to the existence of many
      conflicting hypotheses. We discuss the three main paradigms reported in the
      literature, namely the inhibitor kappaB-alpha (IkappaB-alpha) upregulatory model,
      the protein-protein interaction model and the competition model.

PMID- 10969177
TI  - Molecular mechanisms and Th1/Th2 pathways in corticosteroid regulation of
      cytokine production.
AB  - We focus on how the IL-1 system, T-helper1 (Th1) or Th2 cytokines and
      glucocorticoids, converge to give a unified physiological response.
      Glucocorticoids inhibit IL-1 and IL-1 receptor antagonist (IL-1ra) expression,
      Th1 cytokines stimulate both and Th2 cytokines stimulate IL-1ra and inhibit IL-1.
      Thus, during the Th1 response there is a window for IL-1 inflammatory activity,
      absent during the Th2 response. We also study the interactions among
      glucocorticoid and cytokine transcriptional activity. Glucocorticoids inhibit
      cytokine-induced transcription factors (NFkB, AP1) and cytokines enhance
      glucocorticoid receptor (GR) transcriptional activity, thus reciprocally fine
      tuning immunological control mechanisms.

PMID- 10969178
TI  - Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy.
AB  - Development of CD4+ helper T (Th) cells into type 1 (Th1) or type 2 (Th2)
      effectors, as characterized by their opposite pattern of cytokine production, can
      be influenced by several factors, including hormones. Progesterone promotes the
      production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-gamma
      by T cells. Leukemia inhibitory factor (LIF), essential for embryo implantation,
      is up-regulated by IL-4 and progesterone. Moreover, the production of LIF and/or
      Th2 cytokines by decidual T cells contributes to the maintenance of pregnancy.
      Our results suggest that relaxin and progesterone may contribute to the
      regulation of the immune homeostasis during pregnancy.

PMID- 10969179
TI  - Expression of SOCS genes in normal and leukemic human leukocytes stimulated by
      prolactin, growth hormone and cytokines.
AB  - To evaluate the possible role of the recently described family of suppressors of
      cytokine signaling (SOCS) factors in the human lympho-hemopoietic system, we have
      monitored SOCS factor expression, both constitutive and induced by either
      cytokines, prolactin (PRL) or growth hormone (GH), using polymerase chain
      reaction in normal and leukemic cells. CIS (cytokine-inducible SH2-containing
      protein), SOCS-2 and SOCS-3 were constitutively expressed in peripheral blood
      mononuclear leukocytes. SOCS-3 expression was enhanced by PRL or by IFN-gamma. In
      bone marrow cells and granulocytes, CIS expression was induced and SOCS-2
      enhanced by IFN-gamma and by PRL. In tonsillar cells, CIS expression was
      increased and SOCS-2 was induced by IL-1beta, IL-6, PRL and GH. SOCS-3 expression
      was enhanced by IL-1beta. The expression of SOCS-7 was increased by IL-6, PRL and
      GH. In Raji B-lymphoma cells, the expression of SOCS-2 and SOCS-7 was enhanced by
      IL-1beta. In THP-1 myeloid leukemia cells pretreated with TPA (to induce
      receptors for IFN-gamma), IFN-gamma induced SOCS-2. Jurkat cells expressed more
      SOCS-2 when exposed to PRL. Original observations in this work include the first
      report on SOCS-7 induction by cytokines. Also our data shed new light on the
      possible involvement of PRL and GH in the cytokine network. These hormones could
      modulate the transduction of signals originating from receptors for various
      cytokines.

PMID- 10969180
TI  - Transcriptional regulation of pim-1 by prolactin: independence of a requirement
      for Jak2/Stat signaling.
AB  - Lactogen-dependent Nb2 cell lines have been widely employed to investigate
      signaling mechanisms coupled to prolactin receptor (PRLR)-stimulated
      transcription of hormone-responsive genes. We previously reported that PRL
      rapidly induced expression of the immediate-early protooncogene, pim-1. In the
      present report, we describe experiments conducted to evaluate PRL-stimulated
      transcription of pim-1 as well as potential PRLR-linked signaling mechanisms
      leading to promoter activation. Results from promoter/reporter experiments and
      electrophoretic mobility gel shift analysis indicated that two elements (distal
      element, -427 to -336 bp, and proximal element, -104 to -1 bp) positively
      regulated PRL-stimulated pim-1 promoter activity while it appeared to be
      repressed by factor binding to a NF-1 half site located between these positive
      elements. Deletion of gamma-interferon activation sequences did not reduce the
      effect of PRL to activate the promoter. Results from pharmacological antagonism
      of several signaling mechanisms indicated that PRLR activation of the pim-1
      promoter reflected contributions from the ras-MAPK and PI-3 kinase pathways.
      Together these observations suggest that PRLR stimulation of pim-1 transcription
      occurs independently of a requirement for signaling through a Jak2/Stat
      mechanism.

PMID- 10969181
TI  - Prolactin in autoimmunity and antitumor defence.
AB  - Prolactin (PRL) enhances inflammatory and antitumor responses in vitro and thus
      exhibits Th1-type cytokine-like effects. Evidence from experimental models
      indicates that inhibition of PRL release by bromocriptine downregulates immune
      reactions and ameliorates autoimmune diseases in which Th1 responses are
      predominant. A direct effect of locally produced PRL in some Th1 diseases, such
      as rheumatoid arthritis, supports this concept. Paradoxically, however,
      hyperprolactinemia can also be associated with conditions such as pregnancy,
      where remission of Th1-mediated diseases is known to occur in the context of a
      Th2-dominated milieu. This reversal of the Th1-promoting effect of PRL may be due
      to major changes in the levels of other hormones that can annul and/or override
      the PRL-mediated proinflammatory state. Nevertheless, PRL, as an
      immunopotentiating agent, may have a powerful therapeutic role in cancer and
      other immunocompromised patients.

PMID- 10969182
TI  - Use of human prolactin as a therapeutic protein to potentiate immunohematopoietic
      function.
AB  - The conclusion that prolactin plays a role in immune and hematopoietic function
      was initially based upon observations in hormone deficient animals. The multiple
      cell function defects associated with hypophysectomy or bromocriptine treatment
      were reversed by administration of prolactin. Since these initial observations,
      an increasing body of literature supports prolactin having a role in the immune
      and hematopoietic system. A recombinant form of human prolactin (r-hPRL) has been
      produced and evaluated in a wide variety of preclinical models. Both in vitro and
      in vivo studies suggest that r-hPRL can enhance cell function, accelerate
      lymphoid and myeloid reconstitution and promote hematopoiesis. The multi-lineage
      effect of r-hPRL makes it an attractive candidate for clinical situations
      presenting with immune deficiency or myelosuppression.

PMID- 10969183
TI  - A direct effect of competition on food choice by pigeons.
AB  - Previous research on food choice of pigeons foraging alone and in competition
      showed an indirect response to the competitor, mediated by the resource depletion
      associated with the competitor. This experiment showed, in addition, that pigeons
      can adjust their food choice in direct response to the competitor itself. Pigeons
      foraged for large, preferred grains of maize and smaller, unpreferred grains of
      wheat presented in bowls covered with sawdust. In a within-subject design,
      pigeons were tested alone or in competition with another pigeon. In competition,
      a higher choice proportion of the wheat grains was observed on the first two
      choices out of 48 items, and this effect increased with time in the experiment.
      This result underscores the role of learning in group foraging behaviour. It also
      suggests a possible ecological implication: that individuals that learn faster
      may enjoy a competitive advantage in terms of reduced delay in responding to the
      presence of a conspecific.

PMID- 10969184
TI  - Interaction between positional but not between non-positional cues in human
      predictive learning.
AB  - Four experiments with human subjects examined the cue-interaction effects using a
      computer-controlled predictive learning task. In Phase 1, subjects learned that
      cue P was consistently associated with the occurrence of an outcome (P+), whereas
      cue N was never followed by the outcome (N-). In Phase 2, two neutral cues, R and
      I, were compounded with P and N, respectively. Each compound was followed by the
      outcome (PR+ and NI+). Thus, cue R was compounded with the already predictive cue
      P, whereas cue I was compounded with the non-predictive cue N. In each phase,
      subjects rated the contingency between the different cues and the outcome. In
      experiments 1 and 2, the spatial position of the cues was fixed, whereas it was
      variable in experiments 3, 4a and 4b. Verbal cues were used in experiments 1-3,
      whereas the cues consisted of geometrical figures in experiments 4a and 4b.
      Evidence for cue interaction, as indicated by giving cue I a higher contingency
      rating than cue R after or during Phase 2, was only found under the conditions of
      experiments 1 and 2. The results indicate that the use of positional cues
      facilitates the occurrence of cue-interaction effects. Possible reasons for this
      finding are discussed.

PMID- 10969185
TI  - Generalization of 'same-different' classification abilities in bottlenosed
      dolphins.
AB  - Two bottlenosed dolphins taught to classify pairs of three-dimensional objects as
      either same or different were tested with novel stimulus sets to determine how
      well their classification abilities would generalize. Both dolphins were
      immediately able to classify novel pairs of planar objects, differing only in
      shape, as same or different. When tested on sets of three objects consisting of
      either all different objects or of two identical objects and one different
      object, both dolphins proved to be able to classify 'all different' sets as
      different and 'not all different' sets as same, at levels significantly above
      chance. These data suggest that dolphins can use knowledge about similarity-based
      classification strategies gained from previous training to perform successfully
      in a variety of novel same-different classification tasks. Visual classificatory
      abilities of dolphins appear to be comparable to those that have been
      demonstrated in primates.

PMID- 10969186
TI  - Re-examination of the poisoned-partner effect with the two-bottle testing method.
AB  - Revusky, Coombes and Pohl (Animal Learning and Behavior 10 (1982) 83-90)
      suggested that poisoned conspecifics function as aversive unconditional stimuli
      (USs) for rats (the poisoned-partner effect). The present study re-examines this
      effect with the two-bottle testing method. Rats were first given saccharin and
      later exposed to a poisoned conspecific. They exhibited an aversion to saccharin
      in the subsequent tests involving a choice between saccharin solution and water.
      Furthermore, the subjects that were only exposed to the poisoned conspecific
      later avoided saccharin. The poisoned-partner effect, therefore, can also be
      explained by sensitization. This finding suggests that poisoned conspecifics are
      simply salient stimuli that attract the rat's attention, rather than aversive USs
      of food aversion learning for rats.

PMID- 10969187
TI  - Agonistic and proximity patterns in enclosed mouflon (Ovis gmelini) ewes in
      relation to age, reproductive status and kinship.
AB  - Agonistic and proximity patterns of mouflon sheep (Ovis gmelini) were studied in
      a group of enclosed females during two lambing periods. A non-random linear
      tending hierarchy almost stable over the 2-years was found. Age was correlated to
      social rank and to the distribution of agonistic acts by females. The rank of the
      yearling females was linked to the rank of their mothers. The age of the animal
      and the degree of relatedness with its congeners appeared as main determinants of
      the proximity patterns of ewes. Strong associations between closely related
      females (especially mothers and daughters), brought out the existence of a
      familial structure in mouflon. Otherwise, we found a strong inter-attraction
      between yearlings, which received a large number of aggressions from older
      females. That revealed peer grouping superimposed on familial structures. Age
      also seemed to influence 'sociality' of females, older females tending to
      associate less with conspecifics than younger ones.

PMID- 10969188
TI  - The additive factor method in rat information processing.
AB  - Sternberg introduced the additive factor method as a tool for discovering and
      studying in choice reaction time situations in human subjects. Underlying the
      method is the notion that if information processing consists of successive
      stages, then different factors affecting different stages must have additive
      effects on reaction-time measurements. The additive factor method has been
      extensively used in humans but few attempts have been made to examine whether or
      not additive reaction time patterns were obtainable in rats. In the present work,
      the subjects (13 Long-Evans rats) had to press down a lever and to respond to a
      visual (right or left) stimulus by releasing the lever and introducing the head
      into a lateral (right or left) operandum. The present findings show an additive
      pattern of effects of signal luminance and foreperiod duration on the mean
      reaction time which suggests that we have successfully manipulated two stages of
      rat information processing - the preprocessing stage and the motor adjustment
      stage, respectively. Accordingly, the present study sets the basis for the basis
      for investigating the effects of invasive manipulations (pharmacological and/or
      lesional) on information processing stages.

PMID- 10969189
TI  - Foraging methods can affect patch choice: an experimental study in Mallard (Anas
      platyrhynchos).
AB  - Animals can adapt to changes in feeding conditions by switching between foraging
      methods. Dabbling ducks use different foraging methods, including dabbling in
      deep water with the head and neck submerged, and grubbing in the mud (or shallow
      water) where the eyes are above the surface, so the bird can visually monitor its
      environment while foraging. Deep foraging is considered to provide lower intake
      rates and to have high associated costs, such as predation risk, compared to
      shallow foraging. Ducks should thus prefer shallow foraging and switch to deeper
      methods when feeding conditions deteriorate. We conducted a set of experiments
      with Mallard to assess the importance of intake rate as a cue to choose between
      patches associated with different foraging methods, and evaluate the influence of
      food depletion on the decision to switch between methods. When 50 g of wheat were
      presented in two patches, one at a depth of 5 cm and one at 35 cm, most of the
      foraging was in the shallow area. Reducing food abundance to 10 g in the shallow
      area led to an increase in deep foraging, although the birds still preferred the
      shallow area at the beginning of the tests despite the fact that it did not
      provide a higher intake rate. This area was used until complete depletion, and
      birds did not turn to deep foraging before ensuring that the shallow patch was
      empty. These results show that food depletion affects the choice between feeding
      patches hence foraging method. However the value of intake rate is not the main
      cue for decision, rather the birds appear to choose between patches with
      different methods on account of their respective costs.

PMID- 10969190
TI  - Distinguishing kinds of prior dominance and subordination experiences in males of
      green swordtail fish (Xiphophorus helleri).
AB  - In experiments, there are usually two general ways of obtaining dominants and
      subordinates to test for the effect of recent experience upon ulterior behavior
      and dominance. One is to 'impose' such an experience on the contestants by a
      priori deciding which individual of the pair will become the dominant and which
      will become the subordinate through the use of rigged contests. The second
      technique is to let contestants 'self-select' the winner and loser by waiting for
      the spontaneous outcome of dyadic encounters between two usually well matched
      opponents. These two techniques of obtaining dominants and subordinates probably
      represent extreme cases on a single continuum of investment made by animals to
      settle dominance. To test this, we compared dominants and subordinates obtained
      from these two techniques in Xiphophorus fish males. It was found that pairs
      obtained through rigged contest (R) were much more aggressive in subsequent
      encounters than pairs in which the dominant and subordinate could self-select
      (S). They recuperated more rapidly from handling, initiated contact earlier, took
      more time to assess each other, and fought for a longer period of time. Prior
      winners and prior-losers of the R condition more frequently relied on aggressive
      behavior during contest than that of the S condition. As a consequence, prior
      winners and prior-losers of the R condition won equally the subsequent contest.
      On the contrary, prior-winners of the S condition defeated their prior-loser
      opponent in a majority of cases. These results can be tentatively explained by
      the following principle, winning or losing against a well matched opponent would
      leave more 'experience' than winning over a much weaker opponent, or losing to a
      much stronger one. This reinforces the hypothesis that prior-experiences are not
      qualitative states but come in various degrees.

PMID- 10969191
TI  - Mediation of timing accuracy by operant behavior.
AB  - We attempted to demonstrate that timing performance on a temporal discrimination
      would be enhanced if rats were required to fill a duration with behavior than
      when they were not required to respond. Six rats were trained to discriminate
      between a 3- and 9-s stimulus in a symbolic-matching-to-sample task. In two
      conditions, a tone was used to signal the sample, and in the other two
      conditions, a light was used to signal the sample. In two conditions, the rats
      were required to respond on a lever mounted on the rear wall of the experimental
      chamber before making their discriminative response to one of the two levers
      mounted on the front wall of the experimental chamber. In the other two
      conditions, the rear lever was not presented during sample presentation, and no
      response was required. Consistent with our predictions, timing performance was
      significantly better when a lever-response was required during sample
      presentation than when no response was required.

PMID- 10969192
TI  - Extension of the CS past the US can facilitate conditioning of the rabbit's
      nictitating membrane response.
AB  - Five experiments were conducted in which the onset of a tone conditioned stimulus
      (CS) preceded the unconditioned stimulus (US) by 500 ms. Across experiments, the
      offset of the CS was extended past the offset of the US by values ranging from 0
      ms to 40000 ms. Extensions of the CS of 2000 ms or greater produced acquisition
      of a conditioned response (CR) that was as fast or faster than in the no
      extension condition (0 ms). While extension of a forward tone CS after the US
      enhanced excitatory conditioning, insertion of another CS (light) in a purely
      backward relationship with the US passed only a retardation test, indicative of
      latent inhibition, and not a summation test needed for conditioned inhibition.
      The results add to the evidence that excitatory and inhibitory processes are both
      engaged following US offset. Alternative theories of CS processing are discussed.

PMID- 10969193
TI  - Comparison of the instrumental reinforcer devaluation effect in two strains of
      rats (Wistar and Lister).
AB  - In this experiment, the effect of the reinforcer devaluation upon instrumental
      performance was analysed in two strains of rats (Wistar and Lister): Food
      deprived rats were trained to press a lever for sucrose pellets in a single
      session. Immediately after the fulfilment of this session, half of the Wistar and
      Lister rats received an injection of lithium chloride (LiCl), while the remaining
      animals were injected with a sodium chloride (NaCl) solution. A subsequent
      extinction test showed that the subjects who had received immediate LiCl did not
      press the lever as often as those injected with NaCl. No differences in response
      suppression were found between the two strains of rats. These results also show
      that a single devaluation experience is sufficient for an impact on instrumental
      performance.

PMID- 10969194
TI  - Motor unit recruitment and EMG power spectra during ramp contractions of a
      bifunctional muscle.
AB  - Surface electromyograms (EMGs) were analysed on the short and long head of the
      biceps brachii (BBSH and BBLH) during single (F and S) or dual (F+S) flexion and
      supination tasks. It was confirmed, by the analysis of EMG root-mean-square (RMS)
      values, that the highest activations of BBSH and BBLH were obtained during a
      maximal dual task. This study was essentially concerned with the analysis of
      power spectra data obtained during progressive or ramp contractions (RCs). The
      shape of the power spectra established during the first second of the RCs differs
      between F, S and F+S tasks. Differences in mean power frequency (MPF) calculated
      during RCs would be representative of a recruitment of motor units (MUs) that is,
      at least partly, task-dependent. In order to compare MPF values calculated from
      RCs performed under different mechanical conditions (F, S and F+S), MPF-RMS(PSD)
      relationships have been established (RMS(PSD) being defined as the power spectrum
      density RMS). Both BBSH and BBLH exhibited initial MPF values higher in
      supination RC than in flexion RC. Because of plateau values reached at the same
      level of muscle activation whatever the task performed, the slope of the MPF
      RMS(PSD) relationship was lower in S than in F. These results are in favour of MU
      recruitment that is, at least partly, different in F and in S conditions. Dual
      submaximal tasks seem to mix the activation of the F and S subpopulations of MUs
      as revealed by the spectral parameters obtained during F+S ramp contractions.
      This study could find some implication in the field of muscle rehabilitation or
      reinforcement.

PMID- 10969195
TI  - Criterion validation of surface EMG variables as fatigue indicators using peak
      torque: a study of repetitive maximum isokinetic knee extensions.
AB  - A number of studies have been published that have used variables of the
      electromyogram (EMG) power spectrum during dynamic exercise. Despite these
      studies there is a shortage of studies of the validity of surface EMG
      registrations during repetitive dynamic contractions with respect to fatigue. The
      aim of this study was to investigate if the surface EMG variables mean frequency
      (MNF [Hz]) and the signal amplitude (RMS [microV]) are valid indicators of
      muscular fatigue (defined as "any exercise-induced reduction in the capacity to
      generate force or power output") during maximum repeated isokinetic knee
      extensions (i.e. criterion validity using peak torque). Twenty-one healthy
      volunteers performed 100 isokinetic knee extensions at 90 degrees s(-1). EMG
      signals were recorded from the vastus lateralis, the rectus femoris and the
      vastus medialis of the right thigh by surface electrodes. MNF and RMS of the EMG
      together with peak torque (PT [Nm]) were determined for each contraction. MNF
      showed consequently higher correlation coefficients with PT than RMS did.
      Positive correlations generally existed between MNF and PT. The majority of the
      subjects had positive correlations between RMS and PT (i.e. decreases both in PT
      and in RMS). In conclusion, at the individual level MNF generally - in contrast
      to RMS - showed good criterion validity with respect to biomechanical fatigue
      during dynamic maximum contractions.

PMID- 10969196
TI  - Reciprocal coactivation patterns of the medial and lateral quadriceps and
      hamstrings during slow, medium and high speed isokinetic movements.
AB  - The effect of movement velocity and fatigue on the reciprocal coactivation of the
      quadriceps and hamstrings was investigated through analysis of the root mean
      square (RMS) and the median frequency (MDF) of surface electromyography for the
      vastus medialis (VM), vastus lateralis (VL), medial hamstrings (MH) and biceps
      femoris (BF). Fourteen subjects performed six continuous isokinetic knee
      extension and flexion movements at 60 degrees, 180 degrees and 300 degrees s(-1),
      and 30 continuous movements at 300 degrees s(-1) to examine muscular fatigue
      patterns. Statistical analyses revealed that the RMS activity of the VM displayed
      greater coactivation than the VL (P<0.01) and the BF displayed greater
      coactivation than the MH (P<0.0001). There was no effect of velocity on the
      coactivation levels of the VM, the VL, or the MH; however, there was an effect of
      velocity on the coactivation levels of the BF (P<0.0001). Relative to MDF
      activity, the MH shifted upward as velocity increased (P<0. 01) while the BF
      decreased between 180 and 300 degrees s(-1) (P<0. 01). Results of the muscular
      fatigue test indicated that the RMS activity of the VM showed a higher degree of
      coactivation than the VL (P<0.01) and the BF showed approximately three times the
      coactivation level of the MH (P<0.001). The MDF of the VL and MH shifted downward
      as the repetitions progressed (P<0.01) with no changes for the VM or for the BF.
      Results of this study suggest that during isokinetic testing, both the VM and BF
      have significantly greater reciprocal coactivation levels when compared to the VL
      and MH, respectively. In addition, these results suggest that motor unit
      recruitment patterns of the VM and VL and the MH and BF differ with regard to the
      effects of velocity and fatigue.

PMID- 10969197
TI  - A test of a dual central pattern generator hypothesis for subcortical control of
      locomotion.
AB  - This study was designed to examine the nature of neural circuits involved in
      subcortical inter-limb coordination and reflex modulation mechanisms of
      locomotion. These circuits, called central pattern generators (CPGs), are
      believed to receive tonic input and generate rhythmically alternating sets of
      commands. Although CPGs have been theorized to exist in humans, their potential
      dual role in inter-limb coordination and reflex modulation is unclear. In the
      present study, nine participants walked on a treadmill, timing their heel-strikes
      to a metronome which varied the phase lag from 0.5 to 1.0 pi radians (0.1 pi
      intervals). A stimulus was delivered to the sural nerve and reflexes were
      measured in the ipsilateral and contralateral lower extremities through
      electromyography. The similarity between phase lag conditions for both temporal
      coordination (i.e., relative timing aspects between muscles and/or limbs) and
      reflex intensities suggested that they may be controlled by the same subcortical
      circuitry. Two plausible explanations exist: (1) a single CPG coordinates
      muscular contractions and phasically alters proprioceptive reflex modulation, as
      well as cutaneous input, using feed-forward control; (2) two separate circuits
      are strongly entrained, producing synchronous outputs for inter-limb coordination
      and reflex modulation. The out-of-phase task used in this study was limited in
      discerning such a difference, if it exists.

PMID- 10969198
TI  - A new technique for the selective recording of extensor carpi radialis longus and
      brevis EMG.
AB  - Tennis Elbow or Lateral Epicondylalgia is manifested by pain over the region of
      the lateral epicondyle of the humerus, related to use of the wrist extensor
      muscles. Extensor carpi radialis longus (ECRL) and brevis (ECRB) have been
      implicated in the dysfunction associated with Lateral Epicondylalgia. For muscles
      in the human forearm, particularly those in close proximity, selective recordings
      are nearly impossible without the use of fine wire, indwelling electrodes. These
      can be inserted in precise locations and have small recording areas. Standard
      electromyography texts indicate, however, that the activity of ECRL and ECRB
      cannot be distinguished, even with intramuscular electrodes. We present a new
      technique for determining the most appropriate sites at which to insert
      intramuscular electrodes for selective recordings of ECRB and ECRL. The location
      of ECRB and ECRL was measured on 10 cadaver specimens, 5 right arms and 5 left
      arms. The distance from the muscle origin to (1) insertion, (2) largest portion
      of the muscle belly, (3) most proximal fibres and (4) most distal fibres were
      measured and expressed relative to forearm length. The mean distance and 95%
      confidence interval was calculated for each of the four measures. These data
      indicated a significant separation of the belly of each muscle along the length
      of the forearm. These relative distances were used to mark electrode insertion
      points on three volunteers. Fine wire electrodes were used to record the
      electromyogram in three participants. Each participant was required to perform
      isometric contractions to produce (1) wrist extension torque, (2) radial
      deviation torque, (3) elbow flexion torque and (4) finger extension. The
      electromyographic recordings show clear differentiation of ECRB and ECRL with the
      relative activation patterns reflecting the underlying anatomical organisation of
      the two muscles. This technique provides an important objective method that can
      be used in conjunction with manual muscle testing to provide a means of ensuring
      accurate intramuscular electromyographic recording from these two muscles.

PMID- 10969199
TI  - Comparison of across-subject EMG profiles using surface and multiple indwelling
      wire electrodes during gait.

PMID- 10969200
TI  - An application of pattern recognition for the comparison of trunk muscles EMG
      waveforms between subjects with and without chronic low back pain during flexion
      extension and lateral bending tasks.
AB  - The purpose of the study was twofold: (1) to evaluate the reliability of distance
      measures computed from a principal component analysis (PCA) of electromyographic
      (EMG) waveforms of trunk muscles recorded during standardized trunk movements and
      (2) to evaluate their sensitivity to the load lifted, the trunk range of motion
      (ROM) and to low back status. Thirty-three male subjects (18 normals, 15
      suffering from non specific CLBP) aged between 35-45 years participated. The EMG
      signals from 12 trunk muscles and the kinematics of trunk segments were recorded
      during 12 tasks. The subjects performed flexion-extension and lateral bending
      (left and right) tasks (three complete cycles) with and without a 12 kg load and
      at different trunk ROM (maximal or at defined submaximal angles). Distance
      measures locating each subject relative to a reference PCA model were computed
      for each muscle and task. The reliability of these distance measures was
      evaluated for 10 subjects (five normals and five CLBP) who performed two tasks on
      three different days. The reliability of distance measures was acceptable for
      agonist muscles only. The distance measures were sensitive to the load lifted and
      to the trunk ROM for different muscles and tasks but poorly sensitive to low back
      status. Several reasons that could explain the low sensitivity of these measures
      to low back status are discussed and potential solutions are proposed. A
      procedure based on a reliability analysis is proposed to select the number of
      principal components to include in the reference PCA model. It is expected that
      the refinement of the method used in this study could provide an effective
      clinical tool to assess EMG waveforms of trunk muscles during dynamic tasks.

PMID- 10969201
TI  - Digital filter design for peak detection of surface EMG.
AB  - A simple Low-Pass Differential (LPD) filter is often used for the Motor Unit
      Action Potential (MUAP) peak detection in needle EMG decomposition. Decomposition
      of surface EMG is much more difficult since surface EMG is more mixed than needle
      EMG. A successful peak detection of MUAPs is a first important step for EMG
      decomposition. We found that a simple LPD filter is not suitable for surface MUAP
      detection; instead the Weighted Low-Pass Differential (WLPD) filters are
      proposed. The filter performance is analyzed based on different window selection
      and varying MUAPs from simulated and recorded surface EMG. The sinusoidal WLPD
      filter is found to have better SNR improving factors, and to be more robust under
      the varying conditions.

PMID- 10969202
TI  - [Hormones, platinum, and cancer of the breast].

PMID- 10969203
TI  - [p57KIP2 in muscle differentiation, simpler than CKI].

PMID- 10969204
TI  - [HRT debate (hormone replacement therapy in menopause)].

PMID- 10969205
TI  - [Perhaps an explanation for the therapeutic escape of prostate cancer treated
      with antiandrogens].

PMID- 10969206
TI  - [14-3-3sigma (stratifin), a potential tumor suppressor frequently inactivated by
      methylation in cancer of the breast].

PMID- 10969207
TI  - [Poliovirus against gliomas].

PMID- 10969208
TI  - [Involvement of ephrins and their receptors in oncogenesis].
AB  - Ephrins are membrane-linked ligands with an autocrine and/or immediate paracrine
      action. Ephrins were previously involved in embryonic neurogenesis, axonal
      guidance and/or retraction. Here, we will present data of the literature
      describing their roles in angiogenesis and in tumor progression. The capacity for
      ephrins to act in opposite directions will be discussed.

PMID- 10969209
TI  - [JM216, an orally active platine derivative].

PMID- 10969211
TI  - [Introduction to regression models].
AB  - Regression models are widely used. They are viewed by clinicians as a passport
      for a publication in major journals. The expressions: multivariate, logistic
      regression and Cox model are synonymous with complexity and appear both magical
      and seductive. Altogether, most clinicians do not read the results of regression
      models with a critical eye. Our aim is to describe the most common regression
      models in a unifying framework, and to explain how to interpret each model. We
      hope that investigators will then be able to discuss the models with the
      statisticians.

PMID- 10969210
TI  - [Dependence receptors: links between apoptosis, nervous system development and
      control of tumorigenesis].
AB  - The dependence receptor notion was based on the observation that the effects of a
      number of receptors that function in both nervous system development and
      tumorigenesis (especially metastasis) cannot be explained simply by a positive
      effect of signal transduction induced by ligand binding. Receptors such as the
      common neurotrophin receptor p75NTR, the androgen receptor (AR), DCC (deleted in
      colorectal cancer), and RET (rearranged during transfection) demonstrate effects
      that are more adequately explained when these are considered to be dependence
      receptors. These receptors show two distinct forms of signal transduction
      depending on their respective ligand availability: in the presence of their
      ligands, they transduce a signal for either proliferation or differentiation;
      however, they are not inactive in the absence of their ligands, but rather induce
      an active signal for cell death. Such receptors thus create a cellular state of
      dependence on their ligands, the loss of ligand availability inducing cell
      suicide or enhancing the likelihood of cellular suicide. This new concept is
      reviewed here enlightening the molecular mechanisms of these receptors and their
      potential relevance in vivo in the development of the nervous system and in the
      control of tumorigenesis.

PMID- 10969212
TI  - [Leiomyosarcoma of the right ventricle].
AB  - A 58-year-old woman has dyspnea and palpitations which reveal a leiomyosarcoma of
      the right ventricle. The medical imaging shows a lobulated sessile tumor attached
      to the ventricular septum and the tricuspid valve extending into the pulmonary
      artery trunk. The resection is performed with a tricuspid valvoplasty. In spite
      of chemotherapy (epirubicin-cyclophosphamide), relapse is observed with pulmonary
      metastases 17 months after the surgery. The death becomes on 18 months in
      congestive heart failure. From this case, the authors make a review of the
      literature about this exceptional tumour, and talk over the low possibilities of
      treatment, despite the capacities of the new ways of diagnosis.

PMID- 10969213
TI  - [New trends in assessment in anticancer treatments by phase II clinical trials].
AB  - The aim of phase II clinical trials in oncology is to judge if a new treatment
      have a sufficient antitumor activity to justify further studies. They represent a
      crucial step in a new anticancer therapy development. The aim is to present phase
      II clinical trials planification and interpretation methods, end points, recent
      methods and news in tumor response assessment. Changes of the place of phase II
      clinical trials in a new treatment development strategies are finally shown. Non
      randomized trials planification methods (unique analysis, Gehan's method, Simon's
      procedure, Fleming's multi-stages procedure, triangular test) are described.
      Usual primary end point is tumor size diminution. Some studies are interested in
      secondary end points like survival data or treatment toxicity. New planification
      methods are exposed : randomized phase II clinical trials, phase II within a
      phase III trial, cross-over studies and bayesian theories are presented. Recent
      tumor response evaluation theories ("Recist") are described. Phase II trials
      function in new treatment development is progressing : they could be sufficient,
      in some cases, to allow a temporary marketing authorization if a treatment show
      great efficacy. Global reflection upon new treatment and methods allowing
      marketing authorization is required.

PMID- 10969214
TI  - [Standards, Options and Recommendations (SOR) for the surveillance and the
      prevention of cross infections in oncology. Federation Nationale des Centres de
      Lutte Contre le Cancer].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of the French Cancer Centres
      (FNCLCC), the 20 French Cancer Centres and specialists from French Public
      Universities, General Hospitals and Private Clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary group of experts, with feedback
      from specialists in cancer care delivery. OBJECTIVES: To develop clinical
      practice guidelines according to the definitions of the Standards, Options and
      Recommendations project for the prevention and the surveillance of cross
      infection in oncology. METHODS: Data were identified by searching Medline and the
      personal reference lists of members of the expert groups. Once the guidelines
      were defined, the document was submitted for review to 106 independent reviewers,
      and to the medical committees of the 20 French Cancer Centres. RESULTS: 1)
      Criteria of infection status and nosocomiality defined by the Centers for
      Infectious Diseases (CDC) and Prevention and the Superior Council of Public
      Hygiene (CSHPF) are not adapted and have to be redefined in oncology. 2) The
      epidemiology of nosocomial infections in oncology is not well known but their
      incidence seems to be higher. Numerous risk factors of cross infections coexist
      in cancer patients, among which the duration and depth of neutropenia. 3)
      Surveillance and prevention of cross infection are compulsory and were taken into
      account in the accreditation of hospitals. Obligation is expressed in terms of
      means and results. 4) The objectives of the cross infection surveillance are to
      detect major problems and critic situations, to guide probabilistic antibiotic
      therapy and to assess the effectiveness of the infections control. The
      surveillance means consist in prevalence and incidence survey, punctually and
      continuously conducted. 5) The three specific behaviors to be adopted to prevent
      cross infections are to control: all the patients, infected patients carrying
      multiresistant bacteria, immunodepressed patients. 6) Standards of care have to
      be applied to a/l patients with cancer. 7) It is necessary to add particular
      septic cares for the patients infected with micro-organisms indicated on
      reference lists or carrying multiresistant bacteria. 8) The only objective of the
      protective isolation of immunodepressed cancer patients is to reduce the cross
      infection. There is no standard behavior for the indications and the modalities
      of protective isolation. The prevention behaviors to be taken are defined by
      expert agreements.

PMID- 10969215
TI  - [Incidence of colorectal cancer in Bas-Rhin, trend and prediction in 2009].
AB  - The colorectal cancer is one of the three most frequent cancers. It concerns more
      and more men and women and is a of heavy consequence for mortality and treatment.
      This study attempted to predict the incidence and the number of incident cases of
      colorectal cancer. The analysis is a Poisson regression based on an age-period
      cohort model. The predicted value of the incidence of colon cancer, standardized
      on the world population (25-89 years old), is increasing with time: it is, in
      2005-2009, 41.5 for 100,000 for the women and 104.9 for 100,000 for the men. For
      rectum cancer, the predicted value of incidence is, in 2005-2009, 22.9 for
      100,000 for the women and 37.2 for 100, 000 for the men. During the period 2005
      2009, the number of incident cases is, for colon, 1,195 women (the mean increase,
      every ten years, is 31%) and 2,254 men (the mean increase, every ten years, is
      65%). During the same period, the number of incident cases is, for rectum, 640
      women (the mean increase, every ten years, is 24%) and 807 men (the mean increase
      every ten years is 14%). These results are similar to those of other studies in
      Europe and in the World.

PMID- 10969216
TI  - [Interest of periareolar injection for colorimetric detection of sentinel node in
      breast cancer].
AB  - Most teams working on sentinel node biopsy in the treatment of breast cancer
      inject either radioactive colloid or vital blue dye around the primary tumour.
      Many anatomical studies and lymphoscintigraphical studies, some very old, have
      shown that the lymphatic drainage of the breast is collected first in the
      periareolar plexus of Sappey, then routed to the axilla in 95% of cases, via one
      or two primary collectors. In a series of 94 breast cancers measuring less than 3
      cm, with any palpable axillary lymph node, 2 ml of patent blue was injected
      intradermally around the areola, at the two meridians around the tumor. The
      sentinel node was identified in 89 cases (94,7%), regardless of the location of
      the primary tumor. All the sentinel nodes were located in the lower axilla. An
      average of 1.6 nodes were found per patient. In 41 cases, axillary lymph node
      dissection was performed either immediately (5 technical failures, 9 positive
      frozen section) or delayed only if the sentinel node was positive, either on
      standard H&E staining or on immunohistochemistry (27 cases). Thus, axillary lymph
      node dissection was not performed in 48 patients (55%). In positive node patient,
      the sentinel node was the only positive lymph node in 20 patients (55%). For 5
      positive node patients, axillary lymph node dissection was not performed: poor
      vital status (2 micro-metastatic nodes) or by decision of patient (3 IHC positive
      nodes). With this periareolar injection procedure, the rate of detection is
      highly satisfactory and is comparable to that usually published with peritumoral
      injection. This procedure seems appropriate in all cases, regardless of the
      topography, the size or the multifocality of breast cancer.

PMID- 10969217
TI  - [Rectal carcinoma: critique of surgical reason and other things that must be
      said...].

PMID- 10969218
TI  - Intravenous magnesium sulfate treatment for acute asthma in the emergency
      department: a systematic review of the literature.
AB  - STUDY OBJECTIVES: There is some evidence that magnesium, when infused into
      asthmatic patients, can produce bronchodilation in addition to that obtained from
      standard treatments. This systematic review examined the effect of intravenous
      magnesium sulfate used for patients with acute asthma managed in the emergency
      department. METHODS: Only randomized controlled trials were eligible for
      inclusion. Studies were included if patients presented with acute asthma and were
      treated with intravenous magnesium sulfate versus placebo. Trials were identified
      from the Cochrane Airways Review Group register, which consists of a combined
      search of EMBASE, MEDLINE, and CINAHL databases and hand-searching of 20 key
      respiratory journals. Bibliographies from included studies and known reviews were
      searched. Primary authors and content experts were contacted. Data were extracted
      and methodologic quality was assessed independently by 2 reviewers. Missing data
      were obtained from authors. RESULTS: Seven trials (5 adult, 2 pediatric)
      involving a total of 668 patients were included. Overall, admission to hospital
      was not statistically reduced using magnesium sulfate (odds ratio [OR] 0.31, 95%
      confidence interval [CI] 0.09 to 1.02). In the severe subgroup, admissions were
      reduced in those receiving magnesium sulfate (OR 0.10, 95% CI 0.04 to 0.27).
      Overall, patients receiving magnesium sulfate demonstrated nonsignificant
      improvements in peak expiratory flow rates (PEFR) when all studies were pooled
      (weighted mean difference [WMD] 29 L/min, 95% CI -3 to 62). In studies of
      patients with severe acute asthma, PEFR WMD improved by 52 L/min (95% CI 27 to
      78) favoring magnesium sulfate treatment. The absolute FEV(1) also improved by
      10% predicted (95% CI 4 to 16) in patients with severe acute asthma. No
      clinically important changes in vital signs or side effects were reported.
      CONCLUSION: Current evidence does not clearly support routine use of intravenous
      magnesium sulfate in all patients with acute asthma presenting to the ED.
      However, magnesium sulfate appears to be safe and beneficial for patients who
      present with severe acute asthma. Practice guidelines need to be changed to
      reflect these results.

PMID- 10969219
TI  - Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis.
AB  - STUDY OBJECTIVE: Although several trials have been published evaluating
      intravenous magnesium sulfate as treatment for acute bronchospasm, its
      effectiveness for this indication remains unclear, prompting this meta-analysis.
      METHODS: All randomized controlled trials of adjuvant bolus intravenous magnesium
      sulfate for acute bronchospasm in the emergency department were eligible. Trials
      were identified using MEDLINE, EMBASE, bibliographies of selected articles, and
      review of abstracts of 4 scientific societies. Two reviewers abstracted data, one
      of whom was blinded to author and journal. Because studies used different
      spirometric outcome measures, effect size was calculated for each study by
      Hedges' method. The analysis used a fixed-effects model. One-way sensitivity
      analyses were performed to assess the influence of study quality and to search
      for publication bias. RESULTS: Abstracts from 210 articles were reviewed,
      yielding 40 trials, of which 9 were specific to bolus intravenous magnesium
      sulfate in the ED, in doses from 1.2 to 2 g, or an equivalent pediatric dose.
      Combined results across 9 studies including 859 patients showed a posttreatment
      effect size of 0.162 for patients treated with intravenous magnesium sulfate (95%
      confidence interval 0.028, 0.297; P =.02). In sensitivity analyses exploring the
      effects of study quality and publication bias, the summary effect ranged from
      0.127 to 0.206. No serious adverse events were reported. CONCLUSION: Adjuvant
      bolus intravenous magnesium sulfate in acute bronchospasm appears statistically
      beneficial in improving spirometric airway function by 16% of a SD. Although the
      clinical significance of this is uncertain, given the safety of intravenous
      magnesium sulfate therapy and its relatively low cost, it should be considered,
      absent contraindications, in patients with moderate to severe acute bronchospasm.

PMID- 10969220
TI  - Continuous versus intermittent nebulization of salbutamol in acute severe asthma:
      a randomized, controlled trial.
AB  - STUDY OBJECTIVE: This study was conducted to compare the clinical and spirometric
      effects of continuous and intermittent nebulization of salbutamol in acute severe
      asthma. METHODS: Forty-two consecutive patients presenting to the emergency
      department for acute severe asthma (peak expiratory flow [PEF] mean+/-SD, 24%+/
      12% predicted) were prospectively randomly assigned to receive 27.5 mg of
      salbutamol by either continuous or intermittent nebulization over a 6-hour
      period. The continuous nebulization group received 15 mg of salbutamol during the
      first hour and 12.5 mg over the next 5 hours. The intermittent nebulization group
      received 5 mg of salbutamol every 20 minutes during the first hour and 2.5 mg
      hourly over the next 5 hours. All participants received oxygen and intravenous
      hydrocortisone. Clinical and spirometric assessment was performed at baseline, 40
      minutes, 60 minutes, and at 3 and 6 hours after the start of the nebulization.
      Secondary endpoints were the respective rates of hospitalization and treatment
      failure. RESULTS: A significant clinical and spirometric improvement was observed
      in both groups over baseline as soon as the 40th minute and was sustained
      thereafter (absolute PEF increase at the sixth hour 30%+/-18% and 32%+/-22% in
      the continuous and intermittent nebulization groups, respectively; P <.01 over
      baseline). PEF and the clinical score evolved similarly in both groups. There was
      no difference between the groups regarding the failure rate of the initial
      bronchodilator treatment to terminate the asthma attack (3 [14%] in the
      continuous nebulization group and 2 [9.5%] in the intermittent nebulization
      group, absolute difference 4.5% [95% confidence interval -14% to 23%]). Eight
      (38%) patients and 9 (43%) patients from the continuous and intermittent
      nebulization groups, respectively, required hospitalization according to
      predefined criteria (absolute difference 4.8% [95% confidence interval -24% to
      34%]). CONCLUSION: We did not observe an appreciable difference between
      continuous and intermittent nebulization of salbutamol in acute severe asthma.
      The decision to use one of these nebulization methods should be based on
      logistical considerations.

PMID- 10969221
TI  - Asthma education in the Emergency Department. On behalf of the MARC
      Investigators.
AB  - STUDY OBJECTIVE: We surveyed emergency department-based asthma researchers to
      study the presence of formal asthma education programs (AEPs), and examined data
      from prospective cohort studies to compare sites with and without AEPs. METHODS:
      We contacted site investigators in the Multicenter Airway Research Collaboration
      (MARC) in July 1998 by mail, fax, or telephone. Main outcomes were the percentage
      of sites using AEPs and the percentage of AEPs using each of 7 "key" teaching
      items in national guidelines. MARC data provided site and patient
      characteristics. RESULTS: All 77 site investigators (100%) responded to the
      survey. Using a scale from 1 to 5 (mean+/-SD), respondents identified instruction
      in proper inhaler technique (4.8+/-0.5), "spacer" use (4.3+/-0.7), recognition of
      asthma triggers (4.3+/-0.8), and rationale for medications (4. 6+/-0.6) as
      priorities for teaching. Twelve sites (16%; 95% confidence interval [CI] 8% to
      26%) had AEPs; most (8) were at pediatric sites. Patients presenting to sites
      with AEPs were younger (22+/-16 years versus 25+/-15 years, P <.001), more likely
      to be uninsured (26% versus 23%, P <.001), and less likely to be taking inhaled
      corticosteroids (30% versus 37%, P <.001). AEP sites uniformly stressed "key"
      items, except for "written action plan" (50% of sites) and "peak flow diary" (33%
      of sites). CONCLUSION: Although asthma researchers agree that patient education
      is very important, few EDs involved in asthma research use AEPs. Sites with AEPs
      appear to serve patients at higher risk of poor asthma outcomes. Further study is
      needed to address the effectiveness of AEPs in the ED.

PMID- 10969222
TI  - Results of provider self-adjudication using the prudent layperson standard
      compared with the managed care organization's emergency department claim review
      process.
AB  - STUDY OBJECTIVES: We compare the results of a provider "self-adjudicating"
      outpatient emergency department claims using a "presenting symptom-based" system
      with the managed care organization (MCO) adjudicating the claims using a "final
      diagnosis-based" system. METHODS: All outpatient visits from one MCO to an urban,
      university hospital between January 1, 1998, and February 28, 1999, were
      included. Each record was reviewed by 2 methods to determine whether the visit
      qualified for payment under the MCO's benefit structure. Under the provider
      adjudication, symptom-based system, all visits with nursing triage levels of
      immediate/emergency were approved automatically. Those with triage levels of
      delayed/nonurgent were reviewed by an emergency physician and approved if, in the
      physician's opinion, the presenting symptoms met the emergency criteria under the
      District of Columbia's Access to Emergency Services Act. A second claims review,
      blinded to the first, was performed with the diagnosis-based system used by the
      MCO before approval of the prudent layperson standard. This review divided the
      records into "approve," "deny," and "suspend" categories according to the
      discharge International Classification of Diseases, ninth revision code. The
      results of the 2 reviews were compared. RESULTS: We reviewed 1,830 records; 836
      (46%) cases were triaged as immediate/emergency and 994 (54%) as
      delayed/nonurgent. Of the 994 delayed/nonurgent visits, physician review
      determined that 607 (61%) met the prudent layperson standard and 387 (39%) did
      not. Overall, the provider self-adjudication system determined that 1,443 (78.8%)
      of the 1,830 visits should be approved for insurance coverage. The MCO's system
      approved 966 (53%), denied 335 (18%), and suspended 529 (29%). Provider self
      adjudication using a symptom-based system resulted in the immediate approval of
      1,443 (77.8%) visits compared with 966 (52.7%) by a diagnosis-based system (P
      <.001). Excluding the 529 suspended claims, McNemar's statistical testing of
      1,302 records failed to demonstrate the equivalence of the 2 systems (P <. 001).
      CONCLUSION: Compared with the standard ED claims review process used by the
      managed care industry, provider self-adjudication using a symptom-based system
      approves a greater proportion of visits, avoids rejection of many ED visits, and
      identifies many nonemergency visits that mistakenly appear to be emergencies. The
      possibility of providers and MCOs working together to adjudicate outpatient ED
      claims should be explored.

PMID- 10969223
TI  - Emergency department ultrasound scanning for abdominal aortic aneurysm:
      accessible, accurate, and advantageous.
AB  - STUDY OBJECTIVE: This study was conducted to determine whether emergency
      physicians with relatively limited training and experience can accurately
      identify the presence or absence of abdominal aortic aneurysms (AAAs) by
      performing bedside ultrasound scanning, and to assess the potential impact of
      ultrasound scanning on clinical management. METHODS: Patients in whom AAAs were
      suspected, including those patients older than 50 years presenting with
      abdominal/back pain of unclear origin or presumed renal colic, were eligible for
      study entry. Consenting adults had ultrasound scanning by an emergency physician
      who was not responsible for their primary care. Treating physicians remained
      blinded to the results unless an unexpected AAAs was discovered. Scan accuracy
      was ascertained by comparing our ultrasound results with preselected gold
      standards. The clinical impact of the ultrasound studies was determined by
      comparing the preultrasound and postultrasound assessment sheets that detailed
      the presumed diagnosis, proposed investigations and therapies, and patient
      disposition. RESULTS: Our convenience sample includes 68 scans for AAAs; findings
      of 26 scans were positive, 40 scans yielded negative findings, and 2 scans were
      indeterminate. Scan interpretations were 100% accurate. The ultrasound results
      would have improved the care of 46 patients without adverse sequelae. Ultrasound
      scanning served primarily to exclude AAA in patients who proved not to have
      aneurysms; however, scans also provided significant benefits for those with AAAs
      and improved patient management plans. CONCLUSION: Relative neophytes can perform
      aortic ultrasound scans accurately. These scans appear useful as a screening
      measure in high-risk emergency department patients; they may also aid in rapidly
      verifying the diagnosis in patients who require immediate surgical intervention.

PMID- 10969224
TI  - Emergency transvenous cardiac pacing placement using ultrasound guidance.
AB  - STUDY OBJECTIVE: We describe 9 patients who underwent ultrasound-guided
      transvenous cardiac pacing in which ultrasonographic imaging was used to assist
      and confirm the placement of electrode catheters within the right ventricle.
      METHODS: We prospectively enrolled consecutive patients with complete heart block
      who received emergency ultrasound-assisted transvenous cardiac pacing (TVCP).
      Emergency physicians performed both ultrasound scanning and placement of the TVCP
      electrodes at a busy urban teaching medical center. RESULTS: Real-time ultrasound
      guided TVCP was successful in 8 (88.9%) of the 9 patients studied. The pacing
      catheter was not adequately visualized in 1 patient who ultimately required
      placement by a cardiologist. Echocardiography was useful in identifying pacing
      catheter misplacement and subsequent successful repositioning in 3 patients.
      CONCLUSION: Emergency physicians should be aware that ultrasound technology could
      be useful in assisting TVCP in the emergency department setting. Further
      investigation is required to adequately evaluate this modality as a new
      indication for ED echocardiography.

PMID- 10969225
TI  - Ceruminolytic effects of docusate sodium: a randomized, controlled trial.
AB  - STUDY OBJECTIVE: Assessment of the tympanic membrane is often impeded by the
      presence of cerumen. We compared the ceruminolytic effects of triethanolamine
      polypeptide and docusate sodium in patients with cerumen. METHODS: We conducted a
      prospective, randomized, controlled, double-blind trial on a convenience sample
      of cooperative adult and pediatric patients presenting to a university-based
      emergency department who required removal of cerumen to visualize the tympanic
      membrane. Structured data collection was performed, and the physician determined
      whether visualization of the tympanic membrane was partially or totally obscured
      by cerumen (interobserver agreement, rho=0.79). Patients received intra-aural
      instillation of 1mL of either docusate sodium or triethanolamine polypeptide in a
      liquid form. If not completely cleared within 15 minutes, the external ear canal
      was irrigated with 50 or 100 mL of normal saline solution and additional attempts
      to visualize the tympanic membrane were made. The main outcome was the proportion
      of ears in which the tympanic membrane could be totally visualized after
      ceruminolytic instillation with or without irrigation. This study had 80% power
      to detect a 40% difference between groups in the proportion of totally visualized
      tympanic membranes (chi(2) test, alpha=.05). RESULTS: Of 50 enrolled patients, 23
      received triethanolamine polypeptide and 27 received docusate sodium. Mean
      patient age was 40 years (range 1 to 81 years); 35% were female. Groups were
      similar in age, sex, and proportion of completely obscured tympanic membranes at
      presentation (78%). The ability to completely visualize the tympanic membrane was
      significantly greater after treatment with docusate sodium versus triethanolamine
      polypeptide (81% versus 35%; difference in proportions 47%; 95% confidence
      interval [CI], 22 to 71) particularly in children aged 5 or less (90% versus 0%;
      difference in proportions 89%; 95% CI 50 to 100). CONCLUSION: Docusate sodium
      solution is a more effective ceruminolytic than triethanolamine polypeptide,
      allowing complete or partial visualization of the tympanic membrane in most
      patients after a single application when followed with irrigation. Use of
      docusate sodium as a ceruminolytic should be encouraged, particularly in
      children.

PMID- 10969226
TI  - Dueling meta-analyses.

PMID- 10969227
TI  - Easier breathing?

PMID- 10969228
TI  - The prudent layperson definition: will It work for emergency medicine?

PMID- 10969229
TI  - Emergency departments and uninsured children: an enrollment opportunity.

PMID- 10969230
TI  - Emergency medicine and the debate over the uninsured: a report from the task
      force on health care and the uninsured.

PMID- 10969231
TI  - Evidence-based emergency medicine. Ten challenges at the intersection of clinical
      research, evidence-based medicine, and pain relief.

PMID- 10969233
TI  - In response

PMID- 10969232
TI  - Evidence-based emergency medicine. Feedback: "think or die!".

PMID- 10969234
TI  - The Department of Veterans Affairs' role in Federal Emergency Management.
AB  - The Veterans Health Administration (VHA) has been increasingly called on to
      provide disaster relief health care personnel and other emergency assistance
      since the role of the Department of Veterans Affairs in emergency management was
      expanded by the Federal Response Plan in 1992. This article briefly reviews the
      VHA's emergency management functions currently specified by the Federal Response
      Plan and its present activities in procuring and maintaining antidotes,
      antibiotics, and other pharmaceutical stockpiles to be used in response to
      terrorist incidents involving weapons of mass destruction. In view of VHA's
      national scope and extensive assets, its administration by the government, and
      its critical role in health professional training, there are several additional
      ways that VHA could economically augment the federal government's efforts to
      better support and prepare local jurisdictions for disasters or incidents
      involving weapons of mass destruction, if the required authorization and funding
      were provided.

PMID- 10969235
TI  - Long-acting anticoagulant overdose: brodifacoum kinetics and optimal vitamin K
      dosing.
AB  - Ingestion of long-acting anticoagulant rodenticides such as brodifacoum can lead
      to prolonged and life-threatening coagulopathy. A paucity of conflicting
      information is available on brodifacoum's half-life and elimination
      pharmacokinetics. In addition, the optimal dose, duration, and route of
      administration of vitamin K(1) therapy are unknown. We report the case of a 52
      year-old man who ingested eight 43-g boxes of a rodenticide (d-Con Mouse-Prufe
      II; 0.005% brodifacoum; Reckitt & Colman, Wayne, NJ). This case demonstrates that
      after stabilization with fresh frozen plasma, high-dose oral vitamin K(1) therapy
      ( congruent with 7 mg/kg per 24 hours divided every 6 hours) was effective in
      treating brodifacoum-induced coagulopathy. The concentration of vitamin K(1)
      required for normal coagulation in this case was less than the accepted value of
      1 microg/mL, which is derived from a rabbit model. In this case, brodifacoum
      appears to follow zero-order elimination pharmacokinetics. In future cases of
      patients with ingestions of long-acting anticoagulants who present with
      coagulopathy, it may be useful to obtain serial brodifacoum concentrations to
      determine elimination curves to help predict the duration of oral vitamin K(1)
      therapy.

PMID- 10969236
TI  - Update on emerging infections from the centers for disease control and
      prevention.

PMID- 10969237
TI  - Clinical forensic medicine.

PMID- 10969238
TI  - In memoriam.
AB  - So here's the case: a 41-year-old respiratory therapist comes in with a history
      of a bad headache, now much better. She looks like a rose in the emergency
      department. Goes for a head computed tomographic (CT) scan, which shows a
      subarachnoid hemorrhage. Returns to the department and promptly crashes, needs
      intubation, and starts posturing. She dies about 1 week later.

PMID- 10969239
TI  - Low molecular weight heparin.

PMID- 10969241
TI  - Hypoglycemia and the ABC'S (sugar).

PMID- 10969243
TI  - Emergency department overcrowding.

PMID- 10969245
TI  - New diagnostic tests for pulmonary embolism.

PMID- 10969246
TI  - New diagnostic tests for pulmonary embolism

PMID- 10969247
TI  - Proposed amendments to the bylaws of the american college of emergency physicians

PMID- 10969248
TI  - Combination vaccines: problems and promise.

PMID- 10969249
TI  - Can Haemophilus influenzae type b disease be eliminated from the United States?

PMID- 10969250
TI  - Gastroesophageal reflux and infant apnea.

PMID- 10969251
TI  - Botulinum toxin A in cerebral palsy: functional outcomes.

PMID- 10969252
TI  - Primary vaccination of infants with diphtheria-tetanus-acellular pertussis
      hepatitis B virus- inactivated polio virus and Haemophilus influenzae type b
      vaccines given as either separate or mixed injections.
AB  - OBJECTIVE: The aim of this open, multicenter, randomized trial was to evaluate
      the immunogenicity and reactogenicity of a candidate combined diphtheria-tetanus
      acellular pertussis-hepatitis B virus-inactivated polio virus (DTaP-HBV-IPV)
      vaccine when given as either a mixed or as separate concomitant injections with
      Haemophilus influenzae type b (Hib) vaccine. STUDY DESIGN: A total of 359
      subjects were randomized to receive either DTaP-HBV-IPV/Hib (mixed administration
      - 180 subjects) or DTaP-HBV-IPV + Hib (separate administration in opposite limbs 
      179 subjects) at 2, 3, and 4 months of age. RESULTS: After vaccination,
      seroprotective antibody concentrations against diphtheria, tetanus, hepatitis B,
      and polio viruses and a high (> or = 97%) pertussis vaccine response were seen in
      almost all study participants. All subjects except one in the mixed
      administration group had postvaccination Hib anti-PRP antibody concentrations >
      or = 0.15 microg/mL. Of subjects in the mixed and separate group, 77.2%
      (geometric mean antibody concentration, 2. 62 microg/mL) and 88.6% (geometric
      mean antibody concentration, 4.45 microg/mL) had Hib anti-PRP concentrations > or
      = 1 microg/mL, respectively. The addition of the Hib component to the 5-component
      vaccine did not increase the incidence of local or general reactions. CONCLUSION:
      Both administrations of the candidate vaccine were found to be safe, immunogenic,
      and well tolerated. Although anti-PRP geometric mean antibody concentrations and
      the percent of subjects achieving the 1 microg/mL seroprotective level were lower
      after the mixed administration, they were in the range seen with monovalent Hib
      vaccines or with other DTaP-based/Hib combinations licensed in some European
      countries. Therefore both administrations have the potential to simplify
      childhood immunization.

PMID- 10969253
TI  - Experience with the prevention of invasive Haemophilus influenzae type b disease
      by vaccination in Alaska: the impact of persistent oropharyngeal carriage.
AB  - OBJECTIVES: To report the epidemiology of invasive Haemophilus influenzae type b
      (Hib) disease in high-risk Alaska Native infants before and after universal
      infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996
      after changing Hib vaccine type. STUDY DESIGN: Statewide laboratory surveillance
      for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib
      carriage studies were conducted in 1997 and 1998. RESULTS: The invasive Hib
      disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5
      years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in
      rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies
      in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as
      9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native
      children was <1%. CONCLUSIONS: Although Hib disease has decreased in Alaska, the
      rate of Hib disease and carriage in rural Alaska Natives did not decrease to the
      same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol
      phosphate-outer-membrane protein conjugate vaccine for the first vaccine dose is
      critical to disease control in this population with continued transmission in
      infants <6 months of age. The ability to eliminate Hib carriage and disease may
      be affected by population characteristics, vaccination coverage, and Hib vaccine
      type used. This may pose a challenge to global elimination of Hib.

PMID- 10969254
TI  - The relationship between gastroesophageal reflux and apnea in infants.
AB  - OBJECTIVE: To determine the prevalence and relationship between apnea and
      gastroesophageal reflux (GER) among infants with apparent life-threatening
      events. METHODS: We evaluated 67 infants of ages up to 6 months who had an
      idiopathic apparent life-threatening event as determined by polysomnography and
      pH monitoring. RESULTS: No reflux (pH < 4 for more than 6 seconds) was evident in
      32 infants. Fourteen others had such prolonged reflux that the relationship
      between apnea and reflux could not be evaluated. The 21 remaining infants who had
      episodes of apnea and reflux constituted the study group. In 81% of the apneic
      episodes, no relationship to GER was noted. Apnea preceded reflux in 93.6% of the
      episodes, and only 6.4% of the apneic episodes followed reflux. When apnea
      preceded reflux, the apnea was obstructive in 66.8% of episodes and mixed in
      33.2%. Central apnea was not recorded preceding reflux. CONCLUSIONS: Episodes of
      apnea were seldom associated with GER. However, in those instances when apnea and
      reflux were associated, the predominant sequence of events was obstructive apnea
      and to a lesser extent mixed apnea followed by reflux.

PMID- 10969255
TI  - Mydriatics slow gastric emptying in preterm infants.
AB  - OBJECTIVE: Preterm infants are more likely to have episodes of abdominal
      distention, emesis, and gastric residuals 24 hours after their first screening
      examination for retinopathy of prematurity (ROP) than on the day preceding the
      examination. Because these feeding problems reflect abnormalities in motor
      function, the purpose of this study was to compare antral and duodenal motor
      activity and gastric emptying in preterm infants before and after the
      instillation of mydriatics. STUDY DESIGN: Using a low compliance continuous
      perfusion manometric system, we recorded antral and duodenal fasting motor
      activity in 11 preterm infants before and after the instillation of mydriatics
      for their first screening examination for ROP. Gastric emptying was compared
      before and after the eye examination. RESULTS: Although the number of antral
      motor contractions remained relatively constant throughout the study, duodenal
      motor contractions decreased nearly fourfold after the instillation of mydriatics
      versus that seen before (P <.01). Gastric emptying was significantly delayed
      after the completion of the eye examination compared with that seen before the
      examination (P <.05). CONCLUSION: Current doses of mydriatics inhibit duodenal
      motor activity and delay gastric emptying, and these gastrointestinal effects of
      mydriatics may underlie the feeding difficulties seen in preterm infants on the
      day of screening examinations for ROP.

PMID- 10969256
TI  - An evaluation of botulinum-A toxin injections to improve upper extremity function
      in children with hemiplegic cerebral palsy.
AB  - OBJECTIVE: In a randomized, controlled, single-blind trial, to test the
      hypothesis that botulinum-A toxin (BTA) injections into the upper extremity of
      children with spastic hemiplegia improve upper extremity function. STUDY DESIGN:
      Thirty children with hemiplegia, aged 2.5 to 10 years, were randomly assigned to
      receive: (1) a BTA injection into 1 or more of 3 muscle groups (biceps, volar
      forearm muscles, adductor pollicis) plus occupational therapy or (2) occupational
      therapy alone. Blinded outcomes obtained at baseline and at 1, 3, and 6 months
      included the Quality of Upper Extremity Skills Test (QUEST), goniometry
      measurements, grip strength, and Ashworth scores. The caregiver completed the
      self-care domain of the Pediatric Evaluation of Disability Inventory. RESULTS:
      Twenty-nine subjects completed the study. The QUEST demonstrated a significant
      improvement favoring the treatment group on a 2-way analysis of variance (F =
      4.69, df = 1,83; P =.039). BTA treatment was also associated with an improvement
      in score on the self-care domain of the Pediatric Evaluation of Disability
      Inventory (F = 4.68, df = 1,82; P =.04). CONCLUSIONS: This study supports the
      effectiveness of BTA injections to improve upper extremity function of children
      with hemiplegia who have at least moderate spasticity.

PMID- 10969257
TI  - Isolation and identification of the group B streptococcal toxin CM101 from
      infants with sepsis.
AB  - OBJECTIVE: To determine whether the group B streptococcal (GBS) polysaccharide
      exotoxin CM101, which induces a complement-activated cytokine-driven inflammatory
      response, is present in body fluids of infants with GBS disease. STUDY DESIGN:
      With a sandwich enzyme-linked immunosorbent assay, CM101 was measured in plasma,
      urine, and cerebrospinal fluid from newborn infants who were evaluated for
      possible infection and from older infants with culture-confirmed GBS disease.
      RESULTS: Urine from 11 newborn infants with culture-confirmed early-onset disease
      contained large amounts of CM101 (1.0 to 5.5 mg/48 h). Plasma concentrations were
      62.6 +/- 10.5 microg/mL in these infants and were 69.0 +/- 21.2 microg/mL in 4
      older infants with late-onset disease. Plasma CM101 concentrations did not
      correlate with indexes of illness severity, leukocyte counts, or interleukin-6 or
      interleukin-8 plasma concentrations. CM101 was present in cerebrospinal fluid of
      5 infants with meningitis (8.4 +/- 1.6 microg/mL). CM101 was not found in control
      samples. CM101 isolated from urine had molecular weight and sugar composition
      similar to those obtained from GBS culture media, and they both elicited a
      comparable pathophysiologic response when infused intravenously in lambs.
      CONCLUSIONS: CM101 is present in infants with GBS disease, and it appears to be
      the same as CM101 obtained from GBS culture media.

PMID- 10969258
TI  - Premature infants respond to early-onset and late-onset sepsis with leukocyte
      activation.
AB  - OBJECTIVE: Leukocyte differentiation antigens are expressed on the cell membrane
      during activation. The purpose of this study was to evaluate leukocyte activation
      in premature neonates with sepsis. Paired blood samples from the same individual
      while sick and while convalescent were examined to quantify the expression of
      leukocyte antigens in these clinical states. METHODS: Mononuclear blood cells
      from 21 premature infants (24 to 30 weeks' gestation) were analyzed. The "sick"
      samples were drawn at the time of workup for sepsis; "convalescent" samples were
      drawn 20 days later. Samples were incubated with monoclonal antibodies to the
      lymphocyte antigens CD3, CD19, CD25, CD26, CD71, and CD69 and neutrophil antigens
      CD11b, CD11c, CD13, CD15, CD33, and CD66b. The cells were lysed, fixed, and
      analyzed by flow cytometry. RESULTS: Twenty-one infants enrolled in the study had
      multiple sepsis evaluations and had more than one sample available for a paired
      observation. CD33, CD66b, and CD19 levels were significantly elevated in both the
      presumed sepsis and culture-proven sepsis groups when compared with the samples
      drawn from those same patients when healthy. Expression of CD33 and expression of
      CD66b were correlated, and in a multivariate analysis the elevation of antigen
      expression was predictive of sepsis. CONCLUSIONS: Leukocytes from preterm newborn
      infants respond to infection with an increased expression of CD19, CD33, and
      CD66b on their cell surfaces.

PMID- 10969259
TI  - Cerebral infarction in the term newborn: clinical presentation and long-term
      outcome.
AB  - OBJECTIVE: We evaluated the long-term neurodevelopmental outcome of cranial
      computed tomography (CT)-documented cerebral infarction in term neonates to
      ascertain factors that would help to predict the risk of subsequent
      neurodevelopmental sequelae in early childhood. STUDY DESIGN: From 1983 to 1997,
      all surviving neonates from two level III neonatal intensive care units were
      prospectively identified and subsequently assessed in childhood. Clinical
      presentation was characterized by retrospective chart review and blinded re
      reading of computed tomography (CT) scans. Perinatal events were compared with
      neurodevelopmental outcome. RESULTS: Forty-six children were followed up for a
      mean of 42.1 months (range, 18-164 months). Neurodevelopmental outcome was normal
      in 15 and abnormal in 31. A single disability was present in 8, and multiple
      disabilities were present in 23. Cerebral palsy was present in 22 and cognitive
      impairment in 19. Abnormal findings on neurologic examination at discharge and
      seizures in the neonatal period were associated with the presence of one or more
      childhood disabilities. The site or laterality of the vascular distribution of
      the lesion on neonatal CT did not correlate with long-term outcome. CONCLUSION:
      After cerebral infarction in the neonatal period, one third of term infants have
      normal long-term development. Neonatal seizure history and the findings on
      neurologic examination at discharge help in counseling parents about the possible
      long-term outcome of neonatal stroke.

PMID- 10969260
TI  - Transglutaminase antibodies in children with a genetic risk for celiac disease.
AB  - OBJECTIVES: The transglutaminase (TG) antibody test is accurate in identifying
      celiac disease in symptomatic children. We sought to determine the positive
      predictive value of this test in asymptomatic children at genetic risk for celiac
      disease. STUDY DESIGN: Asymptomatic children with a genetic risk for celiac
      disease were studied to investigate the relationships between TG antibody titer,
      small bowel histology, growth, and clinical features. Small bowel biopsy
      histology was graded by using the system of Marsh. RESULTS: Of 30 children with a
      positive TG antibody test result, 21 (70%) had definite (Marsh score 2 or 3) and
      4 (13%) had possible (Marsh score 1) biopsy evidence of celiac disease. TG
      antibody titer correlated with Marsh score (r = 0.569, P <.01). There was an
      inverse correlation between Marsh score and height z score (r = -0.361, P =. 05).
      CONCLUSIONS: In this group of asymptomatic children screened because of a genetic
      risk, TG antibodies have a positive predictive value of 70% to 83% for biopsy
      evidence of celiac disease and may identify children before clinical features of
      celiac disease develop.

PMID- 10969261
TI  - A trial of oats in children with newly diagnosed celiac disease.
AB  - OBJECTIVE: To determine whether consumption of oats is safe in children with
      newly diagnosed celiac disease who are starting a gluten-free diet. STUDY DESIGN:
      We conducted a self-controlled, open-label, 6-month trial of a commercial oat
      breakfast cereal product. Primary outcome variables were small bowel
      histomorphology and anti-tissue transglutaminase IgA antibody titer. RESULTS: The
      10 children who completed the study were 6.8 +/- 4.0 (mean +/- SD) years of age
      and 5 were male. Over 6.6 +/- 0.7 months, they consumed 24 grams of oat cereal
      per day, or 1.2 +/- 0.9 g/kg/d. Compared with start of study, at completion there
      was a significant decrease in biopsy score (P <.01), intra-epithelial lymphocyte
      count (P <.005), anti-tissue transglutaminase IgA antibody titer (P <.01), and
      number of symptoms (P <.01). CONCLUSIONS: We conclude that consumption of a
      commercially available oat cereal product for 6 months is safe for children with
      celiac disease beginning a gluten-free diet. Studies are needed to determine the
      long-term safety of including oat cereal in the gluten-free diet.

PMID- 10969262
TI  - Case-control study of factors associated with nutritional rickets in Nigerian
      children.
AB  - OBJECTIVE: Because the causes of nutritional rickets in tropical countries are
      poorly understood, we conducted a case-control study to determine factors
      associated with rickets in Nigerian children. STUDY DESIGN: We compared 123
      Nigerian children who had rickets with matched control subjects. Dietary,
      demographic, anthropometric, and biochemical data were collected to assess
      factors related to calcium and vitamin D status, which might predispose children
      to rickets. RESULTS: Mean (+/- SD) daily dietary calcium intake was low in both
      children with rickets and control children (217 +/- 88 mg and 214 +/- 77 mg,
      respectively; P =.64). Children with rickets had a greater proportion of first
      degree relatives with a history of rickets (14.6% vs 3.1%; P <.001), a shorter
      mean duration of breast-feeding (16.0 vs 17.3 months; P =.041), and a delayed age
      of walking (14 vs 12 months; P <.001). Among children with rickets, biochemical
      features suggestive of calcium deficiency included hypocalcemia, extremely low
      calcium excretion, and elevated 1, 25-dihydroxyvitamin D and parathyroid hormone
      values. Median 25-hydroxyvitamin D concentrations were 32 and 50 nmol/L (13 and
      20 ng/mL) in children with rickets and control children, respectively (P <.0001).
      Only 46 subjects with rickets (37%) had 25-hydroxyvitamin D values <30 nmol/L (12
      ng/mL). CONCLUSIONS: Vitamin D deficiency appears unlikely to be the primary
      etiologic factor of rickets in African children. Moreover, low dietary calcium
      intake alone does not account for rickets. Insufficient dietary calcium probably
      interacts with genetic, hormonal, and other nutritional factors to cause rickets
      in susceptible children.

PMID- 10969263
TI  - Longitudinal relationship among growth, nutritional status, and pulmonary
      function in children with cystic fibrosis: analysis of the Cystic Fibrosis
      Foundation National CF Patient Registry.
AB  - OBJECTIVE: To determine prospectively the relationship among growth, nutritional
      status, and pulmonary function over a 4-year period in a large cohort of children
      with cystic fibrosis (CF). STUDY DESIGN: CF Foundation National CF Patient
      Registry data collected from 1991 to 1995 for 968 children (507 male) aged 5 to 8
      years with pancreatic insufficiency and forced expiratory volume in 1 second
      within 60% to 140% of predicted values (FEV(1)%) were analyzed longitudinally.
      Variables hypothesized to affect FEV(1)% included age, sex, z scores for height,
      weight, percent of height-appropriate body weight, and annual number of days
      hospitalized. RESULTS: The significant decline in FEV(1)% was curvilinear and
      dependent on baseline FEV(1)%; children with initial FEV(1)% > or = 90 declined
      2.6 U/y more than those with initial FEV(1)% <90. Boys gained but girls declined
      in z scores for height. Girls decreased in z scores for weight at a greater rate
      than boys. The z scores for weight and percent of height-appropriate body weight
      were significantly associated with longitudinal changes in FEV(1)%, after
      adjustment was done for hospitalizations. CONCLUSIONS: Growth, nutritional
      status, and pulmonary function are not stable in prepubertal children with CF and
      pancreatic insufficiency. Important sex-related differences in growth occur
      before puberty. Growth and nutritional status are associated with changes in
      FEV(1)%, suggesting that nutritional intervention may slow the decline in
      pulmonary function in children with CF.

PMID- 10969264
TI  - Energy expenditure after surgical repair in children with cyanotic congenital
      heart disease.
AB  - OBJECTIVE: Infants with cyanotic congenital heart disease (CCHD) have previously
      been shown to have similar resting energy expenditures (REEs) and elevated total
      energy expenditures (TEEs) compared with age-matched healthy infants. The purpose
      of this investigation was to re-examine the REE and TEE of the same individuals
      at 5 years of age, after surgical repair of the heart defect was done, to
      determine whether metabolic differences persist. STUDY DESIGN: Seven children
      were studied approximately 2.6 years after they underwent surgical repair of CCHD
      along with 10 age-matched healthy children. Indirect calorimetry was used to
      determine REE, and the doubly labeled water method was used to determine TEE and
      body composition. RESULTS: Results were compared with single-factor repeated
      measures analysis of variance. No significant differences were found between
      groups in weight or body composition. No significant differences were found
      between groups in REE, TEE, or the energy expended in physical activity.
      CONCLUSION: We conclude that differences in TEE observed during infancy are no
      longer present in 5-year-old children after they undergo surgical repair of CCHD.
      Furthermore, the individual components of energy expenditure of children with
      CCHD after repair are indistinguishable from those of healthy age-matched
      children.

PMID- 10969265
TI  - Homocysteine levels during fasting and after methionine loading in adolescents
      with diabetic retinopathy and nephropathy.
AB  - OBJECTIVE: To assess plasma homocysteine levels in adolescents and young adults
      with type 1 (insulin-dependent) diabetes with and without microvascular
      complications. STUDY DESIGN: Homocysteine levels were measured during fasting and
      after methionine loading in plasma of 61 patients with onset of diabetes before
      the age of 12 years and duration of disease longer than 7 years. They had an
      albumin excretion rate (AER) between 20 and 200 microg/min in 2 of 3 overnight
      urine collections in a period of 6 months and/or retinopathy. Patients with
      persistent microalbuminuria were divided into 2 groups: subjects with AER of 20
      to 70 microg/min and patients with AER of 70 to 200 microg/min. Adolescents (n =
      54) without signs of diabetic retinopathy or nephropathy and matched control
      subjects (n = 63) were also studied. RESULTS: Homocysteine concentrations before
      and after methionine load were higher in adolescents with diabetic complications
      than in healthy subjects (fasting values: 12. 4 +/- 7.9 micromol/L vs 7.8 +/- 4.2
      micromol/L; P <.01; after methionine load: 28.1 +/- 13.2 micromol/L vs 16.6 +/-
      7.3 micromol/L; P <.005). Values of 11.9 micromol/L or higher were considered to
      constitute fasting hyperhomocysteinemia. The increase of homocysteine
      concentrations was particularly evident in young diabetic patients with AER >70
      microg/min (fasting values: 14.7 +/- 5.6 micromol/L; after methionine load: 34.2
      +/- 12.6 micromol/L) and in patients with proliferative retinopathy (fasting
      values: 15.1 +/- 5.0 micromol/L; after methionine load: 36.8 +/- 12.5
      micromol/L). CONCLUSIONS: Increased plasma homocysteine concentrations may
      contribute to increased morbidity and death from cardiovascular disease in
      adolescents and young adults with diabetic retinopathy and nephropathy.

PMID- 10969266
TI  - Auditory brainstem response findings in Rett syndrome: stability over time.
AB  - OBJECTIVE: To determine whether changes consistent with the presence of white
      matter neurodegenerative disease would be observed in the auditory brainstem
      response (ABR) in Rett syndrome in conjunction with age advancement. STUDY
      DESIGN: Initial and follow-up ABR findings were analyzed in a sample of 27 female
      patients with Rett syndrome. The interval between ABR tests ranged from 1 to 9
      years. RESULTS: No significant group differences consistent with
      neurodegenerative disease were observed in the wave I-III, III-V, or I-V
      interpeak latency intervals between the initial and follow-up test sessions.
      CONCLUSIONS: Rett syndrome is not a disorder characterized by progressive white
      matter degeneration affecting the integrity of the brainstem central auditory
      pathways.

PMID- 10969267
TI  - Osteogenesis imperfecta in childhood: prognosis for walking.
AB  - OBJECTIVES: We studied the predicted value of disease-related characteristics for
      the ability of children with osteogenesis imperfecta (OI) to walk. STUDY DESIGN:
      The severity of OI was classified according to Sillence. The parents were asked
      to report the age at which the child achieved motor milestones, the fracture
      incidence, and the age and localization of the first surgical intervention. The
      present main means of mobility was classified according to Bleck. RESULTS: There
      were 76 replies to the 98 questionnaires, of which 70 were included (type I, 41;
      type III, 11; type IV, 18). The type of OI was strongly associated with current
      walking ability, as was the presence of dentinogenesis imperfecta. Patients with
      type III and IV had a lower chance of ultimately walking compared with those with
      type I. Children with more than 2 intramedullary rods in the lower extremities
      had a reduced chance of walking than patients without rods. Rolling over before 8
      months, unsupported sitting before 9 months, the ability to get in sitting
      position without support before 12 months, and the ability to get in a standing
      position without support before 12 months showed positive odds ratios. In Bleck >
      or = 4, multivariate analysis revealed that only the presence of rodding (yes/no)
      in the lower extremities had additional predictive value to the type of OI. The
      presence of dentinogenesis imperfecta and rodding (yes/no) had additional value
      in Bleck > or = 5. CONCLUSION: The type of OI is the single most important
      clinical indicator of the ultimate ability to walk. Information about motor
      development adds little. The early achievement of motor milestones contributes to
      the ability of independent walking when the type of OI is uncertain.
      Intramedullary rodding of the lower extremities is primarily related to the
      severity of the disease and in this way provides consequences for the ability to
      walk.

PMID- 10969268
TI  - Intravenous pamidronate treatment of polyostotic fibrous dysplasia associated
      with the McCune Albright syndrome.
AB  - OBJECTIVES: An open trial of pamidronate treatment was undertaken in 5 children
      and 4 young adults with polyostotic fibrous dysplasia associated with McCune
      Albright syndrome to assess clinical response, bone turnover, and cardiovascular
      status over a 2-year period. STUDY DESIGN: Pamidronate was administered by
      intravenous infusion 1 mg/kg/d for 3 days every 6 months for 2 years. Bone
      turnover was measured at 0, 6, 12, 18, and 24 months with bone mineral density,
      and cardiac output was assessed by echocardiography at 0, 12, and 24 months.
      RESULTS: All subjects reported marked reduction in bone pain and sustained
      increased mobility. The fracture rate decreased in most. Orthopedic insertion of
      intramedullary rods was successful with maintenance of rod position. Mean
      osteocalcin levels fell from 35.5 +/- 5.6 microg/L to 28.4 +/- 4.1 microg/L (P
      <.03). Other bone turnover marker changes were not significant. The mean bone
      mineral density at lumbar spine increased from 0.5 +/- 0.08 to 0.67 +/- 0.03
      g/cm(2) (P <.002) in children and 1.16 +/- 0.6 to 1.33 +/- 0.08 g/cm(2) in adults
      (P <.005). Other changes in bone mineral density were not significant. Cardiac
      output did not change significantly. CONCLUSIONS: Pamidronate treatment is an
      effective therapeutic modality for children with polyostotic fibrous dysplasia,
      with a good short-term safety profile. Failure to demonstrate major biochemical
      or bone densitometry improvements is due to the nature of the fibrous dysplasia
      and intercurrent microfracture.

PMID- 10969270
TI  - The pneumococcal protein conjugate vaccines.

PMID- 10969269
TI  - Osteoporosis pseudoglioma syndrome: treatment of spinal osteoporosis with
      intravenous bisphosphonates.
AB  - OBJECTIVES: To determine whether intravenous bisphosphonate treatment is helpful
      for children with osteoporosis pseudoglioma syndrome who have severe
      osteoporosis. METHODS: Three children (ages 9 to 11 years) with osteoporosis
      pseudoglioma syndrome who had multiple vertebral collapse were treated over a 2
      year period with intermittent intravenous bisphosphonate infusions (pamidronate
      in 2, clodronate in 1). The responses to therapy were assessed with clinical and
      radiographic evaluation and bone densitometry of the spine. RESULTS: All 3
      subjects reported early reductions in bone pain and improved mobility.
      Radiographs showed dense new bone in the vertebral end plates and remodeling of
      the vertebral bodies. Areal bone mineral density at the lumbar spine (age
      appropriate SD score) improved from a mean of -4.5 before treatment to -2.8 after
      2 years (P <.05). No new fractures occurred, and side effects were minimal.
      Growth and pubertal development proceeded normally. CONCLUSIONS: Intravenous
      bisphosphonate therapy appears safe and beneficial in patients with this
      condition and may prevent progressive vertebral deformity.

PMID- 10969271
TI  - Increased oxidative stress in kwashiorkor.
AB  - To test the hypothesis that kwashiorkor is associated with increased oxidative
      stress, urinary concentrations of 2 oxidized amino acids, o,o '-dityrosine and
      ortho -tyrosine, were measured by gas chromatography-mass spectrometry. Children
      with kwashiorkor, with or without infection, had a 3- to 7-fold increase in
      urinary o,o '-dityrosine and a 1.5- to 2-fold increase in ortho -tyrosine when
      compared with well-nourished children. This observation raises the possibility
      that oxidative damage to proteins and other biologic targets plays a role in the
      clinical manifestations of kwashiorkor.

PMID- 10969272
TI  - Partial oculomotor nerve palsy associated with elevated anti-galactocerebroside
      and anti-GM1 antibodies.
AB  - An 11-year-old girl had a painless oculomotor nerve palsy confined to the
      inferior division. Anti-galactocerebroside and anti-GM1 antibodies were elevated
      during the acute phase and decreased to normal limits with clinical improvement,
      suggesting a possible autoimmune basis for this mononeuropathy.

PMID- 10969273
TI  - Acute neurologic decompensation in an infant with cobalamin deficiency exposed to
      nitrous oxide.
AB  - After exposure to nitrous oxide, an infant with unrecognized cobalamin deficiency
      developed neurologic deterioration and pancytopenia. Hematologic recovery and
      partial resolution of his neurologic changes followed repletion of the vitamin.
      Nitrous oxide depletes bioavailable cobalamin and may be a dangerous anesthetic
      in patients with cobalamin deficiency.

PMID- 10969274
TI  - Detection of infant's heart beat/pulse by caregivers: a comparison of 4 methods.
AB  - Parents (n = 200) were asked to find and then count their infant's pulse using 4
      methods: listening to the apex, palpating the apex beat, and palpating the
      carotid and brachial pulses. Listening to the apex method was the fastest and
      most accurate method of heartbeat detection.

PMID- 10969275
TI  - Major advances in pediatric cardiology in the 20th century: I. Diagnostics.

PMID- 10969276
TI  - Correlates of lipoprotein(a) levels in a biracial cohort of young girls.

PMID- 10969278
TI  - Reply

PMID- 10969277
TI  - Hyper-IgD syndrome and familial Hibernian fever are true periodic fever
      syndromes.

PMID- 10969279
TI  - Reply

PMID- 10969281
TI  - Reply

PMID- 10969280
TI  - Idiopathic copper toxicosis.

PMID- 10969282
TI  - Iron deficiency in children with lead exposure.

PMID- 10969283
TI  - Reply

PMID- 10969284
TI  - On mice and men: An autosomal recessive syndrome of chronic recurrent multifocal
      osteomyelitis and congenital dyserythropoietic anemia.

PMID- 10969289
TI  - PCA is effective for older patients--but are there limits?

PMID- 10969290
TI  - Keeping a cool head.

PMID- 10969291
TI  - Age is not an impediment to effective use of patient-controlled analgesia by
      surgical patients.
AB  - BACKGROUND: Obstacles to the use of patient-controlled analgesia (PCA) by elderly
      surgical patients have not been well-documented. Age differences in preoperative
      psychological factors, postoperative pain and analgesic consumption, treatment
      satisfaction, and concerns regarding PCA were measured to identify factors
      important to effective PCA use. METHODS: Preoperatively, young (mean age +/- SD,
      39 +/- 9 yr; n = 45) and older (mean age +/- SD, 67 +/- 8 yr; n = 44) general
      surgery patients completed measures of attitudes toward and expectations of
      postoperative pain and PCA, psychological distress, health opinions, self
      efficacy, and optimism. On the first 2 postoperative days, pain at rest and with
      movement and satisfaction with pain control were assessed using visual analog
      scales. Daily opioid intake was recorded. When PCA was discontinued, satisfaction
      and concerns about it were assessed. RESULTS: The older patients expected less
      intense pain (P </= 0.003) and preferred less information about (P </= 0.02) and
      involvement in (P </= 0.002) health care than young patients. There were no age
      differences with regard to pain at rest (P </= 0.22) or with movement (P </=
      0.68). The older group self-administered less opioid than the young group (P </=
      0.0001) and received PCA for more days than the young group (P </= 0.004). The
      groups did not differ in concerns about pain relief, adverse drug effects,
      including opioid addiction, and equipment use or malfunction. Satisfaction with
      PCA was high and did not differ between the groups. CONCLUSIONS: Patient
      controlled analgesia use was not hindered by age differences in beliefs about
      postoperative pain and opioids. Younger and older patients attained comparable
      levels of analgesia and were equally satisfied with their pain control.

PMID- 10969292
TI  - Cerebral hyperthermia in children after cardiopulmonary bypass.
AB  - BACKGROUND: Cerebral hyperthermia after hypothermic cardiopulmonary bypass has
      been poorly documented for adults and never in children. This study was designed
      to monitor brain temperature during and up to 6 h after cardiopulmonary bypass in
      infants and children. METHODS: Fifteen infants and children, between 3 months and
      6 yr of age, were studied. A right retrograde jugular bulb catheter was used to
      measure the jugular venous bulb temperature (JVBT) during the procedure and the
      first 6 h in the critical care unit. The temperature of the blood from the bypass
      machine was measured at the aorta through the cannula using an indwelling
      temperature probe. All data were acquired every minute. RESULTS: The age of the
      patients ranged from 3 to 71 months (median, 15 months). The mean weight was 11.5
      +/- 8.4 kg. The mean JVBT recorded at the end of cardiopulmonary bypass was 36.9
      +/- 1.4 degrees C but reached 39.6 +/- 0.8 degrees C after six h (P < 0.01). The
      kinetics of brain rewarming was determined by the slope of the mean JVBT and
      corresponded to y +/- 0.006x + 37.21 (r2 = 0.97). The JVBT differed from the
      tympanic temperature after 200 min (P < 0.01) and the lower esophageal (P < 0.05)
      and rectal (P < 0.001) temperatures after 300 min. After 6 h, the tympanic,
      rectal, and lower esophageal temperatures were 37.8 +/- 0.9, 37.7 +/- 0.6, and
      38.4 +/- 0.7 degrees C, respectively, whereas the JVBT was 39.6 +/- 0.8 degrees C
      (P < 0.001). However, the correlation coefficients between the JVBT and the
      tympanic, rectal, and esophageal temperatures were 0.98, 0. 85, and 0.97,
      respectively. No complications were recorded with placement of the jugular bulb
      catheter. CONCLUSIONS: Mean JVBT was significantly increased over the mean core
      temperature at all times from rewarming by cardiopulmonary bypass onward.
      Although the lower esophageal, rectal, and tympanic temperatures correlated well
      with JVBT, all three failed to reflect JVBT during recovery. This observation
      might help to elucidate factors involved in the functional and structural
      neurologic injury known to occur in pediatric patients.

PMID- 10969293
TI  - Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in
      healthy volunteers.
AB  - BACKGROUND: A new pulmonary drug delivery system produces aerosols from
      disposable packets of medication. This study compared the pharmacokinetics and
      pharmacodynamics of morphine delivered by an AERx prototype with intravenous
      morphine. METHODS: Fifteen healthy volunteers were enrolled. Two subjects were
      administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4
      mg over 3 min by intravenous infusion. Thirteen subjects were given twice the
      above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial
      blood sampling was performed every minute during administration and at 2, 5, 7,
      10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The
      effect of morphine was assessed by measuring pupil diameter and ventilatory
      response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses
      were performed simultaneously using mixed-effect models. RESULTS: The
      pharmacokinetic data after intravenous administration were described by a three
      exponent decay model preceded by a lag time. The pharmacokinetic model for
      administration by inhalation consisted of the three-exponent intravenous
      pharmacokinetic model preceded by a two-exponent absorption model. The authors
      found that, with administration by inhalation, the total bioavailability was 59%,
      of which 43% was absorbed almost instantaneously and 57% was absorbed with a half
      life of 18 min. The median times to the half-maximal miotic effects of morphine
      were 10 and 5.5 min after inhalation and intravenous administration, respectively
      (P < 0.01). The pharmacodynamic parameter ke0 was approximately 0.003 min-1.
      CONCLUSIONS: The onset and duration of the effects of morphine are similar after
      intravenous administration or inhalation via this new pulmonary drug delivery
      system. Morphine bioavailability after such administration is 59% of the dose
      loaded into the dosage form.

PMID- 10969294
TI  - Core cooling by central venous infusion of ice-cold (4 degrees C and 20 degrees
      C) fluid: isolation of core and peripheral thermal compartments.
AB  - BACKGROUND: Central venous infusion of cold fluid may be a useful method of
      inducing therapeutic hypothermia. The aim of this study was to quantify systemic
      heat balance and regional distribution of body heat during and after central
      infusion of cold fluid. METHODS: The authors studied nine volunteers, each on two
      separate days. Anesthesia was maintained with use of isoflurane, and on each day
      40 ml/kg saline was infused centrally over 30 min. On one day, the fluid was 20
      degrees C and on the other it was 4 degrees C. By use of a tympanic membrane
      probe core (trunk and head) temperature and heat content were evaluated.
      Peripheral compartment (arm and leg) temperature and heat content were estimated
      with use of fourth-order regressions and integration over volume from 18
      intramuscular thermocouples, nine skin temperatures, and "deep" hand and foot
      temperature. Oxygen consumption and cutaneous heat flux estimated systemic heat
      balance. RESULTS: After 30-min infusion of 4 degrees C or 20 degrees C fluid,
      core temperature decreased 2.5 +/- 0.4 degrees C and 1.4 +/- 0.2 degrees C,
      respectively. This reduction in core temperature was 0.8 degrees C and 0.4
      degrees C more than would be expected if the change in body heat content were
      distributed in proportion to body mass. Reduced core temperature resulted from
      three factors: (1) 10-20% because cutaneous heat loss exceeded metabolic heat
      production; (2) 50-55% from the systemic effects of the cold fluid per se; and
      (3) approximately 30% because the reduction in core heat content remained
      partially constrained to core tissues. The postinfusion period was associated
      with a rapid and spontaneous recovery of core temperature. This increase in core
      temperature was not associated with a peripheral-to-core redistribution of body
      heat because core temperature remained warmer than peripheral tissues even at the
      end of the infusion. Instead, it resulted from constraint of metabolic heat to
      the core thermal compartment. CONCLUSIONS: Central venous infusion of cold fluid
      decreases core temperature more than would be expected were the reduction in body
      heat content proportionately distributed. It thus appears to be an effective
      method of rapidly inducing therapeutic hypothermia. When the infusion is
      complete, there is a spontaneous partial recovery in core temperature that
      facilitates rewarming to normothermia.

PMID- 10969295
TI  - Risk factors for early-onset, ventilator-associated pneumonia in critical care
      patients: selected multiresistant versus nonresistant bacteria.
AB  - BACKGROUND: Ventilator-associated pneumonia is the leading nosocomial infection
      in critically ill patients. The frequency of ventilator-associated pneumonia
      caused by multidrug-resistant bacteria has increased in recent years, and these
      pathogens cause most of the deaths attributable to pneumonia. The authors,
      therefore, evaluated factors associated with selected multidrug-resistant
      ventilator-associated pneumonia in critical care patients. METHODS: The authors
      prospectively recorded potential risk factors at the time of intensive care unit
      admission. An endotracheal aspirate was obtained in all patients who met clinical
      criteria for pneumonia. Patients were considered to have ventilator-associated
      pneumonia only when they met the clinical criteria and aspirate culture was
      positive for bacteria 48 h or more after initiation of mechanical ventilation.
      Pediatric patients were excluded. Adult patients with ventilator-associated
      pneumonia were first grouped as "early-onset" (< 5 days) and "late-onset,"
      determined by episodes of ventilator-associated pneumonia, and then, assigned to
      four groups based on the bacteria cultured from their tracheal aspirates:
      Pseudomonas aeruginosa, Acinetobacter baumanii, methicillin-resistant
      staphylococci, and all others. The first three bacteria were considered to be
      multidrug resistant, whereas the others were considered to be antibiotic
      susceptible. Potential risk factors were evaluated with use of univariate
      statistics and multivariate regression. RESULTS: Among 486 consecutive patients
      admitted during the study, 260 adults underwent mechanical ventilation for more
      than 48 h. Eighty-one patients (31%) experienced 99 episodes of ventilator
      associated pneumonia, including Pseudomonas(33 episodes), methicillin-resistant
      staphylococci (17 episodes), Acinetobacter(9 episodes), and nonresistant bacteria
      (40 episodes). Sixty-six of these episodes were early onset and 33 episodes were
      late onset. Logistic regression analysis identified three factors significantly
      associated with early-onset ventilator-associated pneumonia caused by any one of
      the multidrug-resistant bacterial strains: emergency intubation (odds ratio, 6.4;
      95% confidence interval, 2.0-20.2), aspiration (odds ratio, 12.7; 95% confidence
      interval, 2.4-64.6), and Glasgow coma score of 9 or less (odds ratio, 3.9; 95%
      confidence interval, 1.3-11.3). A. baumanii-related pneumonia cases were found to
      be significantly associated with two of these factors: aspiration (odds ratio,
      14.2; 95% confidence interval, 1.5-133.8) and Glasgow coma score (odds ratio,
      6.0; 95% confidence interval, 1.1-32.6). CONCLUSIONS: The authors recommend that
      patients undergoing emergency intubation or aspiration or who have a Glasgow coma
      score of 9 or less be monitored especially closely for early-onset multidrug
      resistant pneumonia. The occurrence of aspiration and a Glasgow coma score of 9
      or less are especially associated with pneumonia caused by A. baumanii.

PMID- 10969296
TI  - Temporal relation between acoustic and force responses at the adductor pollicis
      during nondepolarizing neuromuscular block.
AB  - BACKGROUND: Contracting muscle emits sounds. The purpose of this study was to
      compare the time course of muscular paralysis at the adductor pollicis muscle
      (AP) with use of acoustic myography and mechanomyography. METHODS: Thirteen
      elective surgery patients, American Society of Anesthesiologists physical status
      I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general
      anesthesia. Force of AP was measured with use of a strain gauge, and sounds were
      recorded simultaneously with use of a small condenser microphone fixed on the
      palmar surface of the hand over the AP. Supramaximal stimulation was applied to
      the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train
      of-four stimulation was also recorded during recovery. RESULTS: Force and sounds
      both were equally sensitive in measuring maximum block. The relation between
      sound and force was curvilinear, with good agreement near 0 and 100% and acoustic
      response exceeding mechanical response at intermediate levels of block. The
      acoustic signal had a slower onset and a faster recovery than the force response.
      The fade response of sound to train-of-four stimulation also recovered faster
      than that of force. CONCLUSION: Acoustic myography is an alternative method to
      monitor muscular paralysis that is easy to set up and applicable to most
      superficial muscles. However, the time course of relaxation at AP using acoustic
      myography differs from the time course of force relaxation. Therefore, these two
      methods are not equivalent when applied to AP.

PMID- 10969297
TI  - Predictive accuracy of target-controlled propofol and sufentanil coinfusion in
      long-lasting surgery.
AB  - BACKGROUND: The predictive accuracy of target concentration infusions of propofol
      has been documented only for less than 4 h, and no prospective study of
      sufentanil target controlled infusion is available. The authors investigated the
      predictive accuracy of pharmacokinetic models for propofol and sufentanil
      coadministered during long-lasting surgery. METHODS: Ten patients, American
      Society of Anesthesiologists physical status I and II, were studied during
      extended cervicofacial surgery. Target controlled infusion of propofol and
      sufentanil was administered during surgery using decisional algorithms, taking
      into consideration pain assessment, hemodynamic changes, and peroperative blood
      losses. Intrasubject data analysis included calculation of performance error,
      median performance error, median absolute performance error, divergence, and
      wobble. RESULTS: The range of plasma target concentrations was 2-5 microgram/ml
      for propofol and 0.2-1 ng/ml for sufentanil. Median performance error was -12.1%
      for propofol and -10% for sufentanil. The wobble values were 11.6% and 22.3% for
      propofol and sufentanil, respectively. The pharmacokinetic sets used slightly
      overpredicted the concentrations, with negative values of divergence of 2.92% and
      0.22% units/h for propofol and sufentanil, for a mean infusion period of 762 min.
      CONCLUSIONS: This prospective study demonstrates the predictive accuracy of the
      pharmacokinetic model for sufentanil infusion and confirms that for propofol
      during long-lasting surgery using standardized rules for the management of target
      controlled infusion and blood loss replacement.

PMID- 10969298
TI  - Optimal propofol plasma concentration during upper gastrointestinal endoscopy in
      young, middle-aged, and elderly patients.
AB  - BACKGROUND: Suitable propofol plasma concentrations during gastroscopy have not
      been determined for suppressing somatic and hemodynamic responses in different
      age groups. METHODS: Propofol sedation at target plasma concentrations from 0.5
      to 4.0 microgram/ml were performed randomly in three groups of patients (23 per
      group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group
      1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in
      which 50% of patients do not respond to these different stimuli were determined
      by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy
      (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were
      also investigated in the different age groups. RESULTS: Cp50ls concentrations
      were 2.23 microgram/ml (group 1), 1.75 microgram/ml (group 2), and 1.40
      microgram/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34
      microgram/ml, respectively, which were significantly higher than their respective
      Cp50ls values. Cp50endo value in group 3 was 1.64 microgram/ml, which was close
      to its Cp50ls value. Because of a high degree of interpatient variability,
      Cp50gag could not be defined. Systolic blood pressure response decreased with
      increasing propofol concentrations. CONCLUSIONS: The authors determined the
      propofol concentration necessary for gastroscopy and showed that increasing age
      reduces it. Propofol concentration that suppresses somatic response induces loss
      of consciousness in almost all young patients.

PMID- 10969299
TI  - Gender affects report of pain and function after arthroscopic anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: Gender-related differences in pain have been clearly shown in
      experimental settings. Clinical studies of such differences have produced
      conflicting findings. No studies have shown a significant difference in pain
      experience associated with differences in functional outcomes. Arthroscopic
      anterior cruciate ligament reconstruction (AACLR) produces pain of moderate
      intensity and provides a useful setting for examining gender-related differences
      in pain and function. METHODS: This study was a retrospective review of
      prospectively gathered data collected for a continuous quality improvement
      program and involved all patients who underwent AACLR at a single outpatient
      facility since June 1992. Anesthetic, surgical, and perioperative management
      techniques were standardized. Using a questionnaire, all patients were routinely
      asked to record pain scores, narcotic consumption, and whether they were able to
      perform a standardized straight leg-raising maneuver on each of the first 5
      postoperative days. RESULTS: A total of 736 patients were enrolled for surgery,
      58% of whom completed the entire 5-day questionnaire. Women reported higher pain
      scores at rest as well as with activity on postoperative day 1 compared with men
      (P < 0.005). In addition, fewer women were able to perform the straight leg
      raising maneuver on postoperative day 1 (P = 0.002) and postoperative day 2 (P =
      0.004). There was no difference in the amount of narcotics consumed at any time
      during the study period. CONCLUSIONS: Women seem to experience greater intensity
      of pain after AACLR that is associated with a decrease in an intermediate measure
      of functional outcome. These differences may result from differences in either
      response to analgesics or neuroprocessing.

PMID- 10969300
TI  - Midazolam: effects on amnesia and anxiety in children.
AB  - BACKGROUND: The minimum time interval between administration of oral midazolam
      and separation of children from their parents that ensures good anterograde
      amnesia has not been previously determined. This is of particular importance in a
      busy operating room setting where schedule delays secondary to midazolam
      administration may not be tolerated. METHODS: Children (n = 113) undergoing
      general anesthesia and surgery completed preoperative baseline memory testing
      using a validated series of picture cards and were randomly assigned to one of
      three midazolam groups or a control group. Exactly, 5, 10, or 20 min after
      receiving oral midazolam (0.5 mg/kg) or 15 min after receiving placebo, children
      were administered a second memory test that used pictures. Anxiety of children
      was assessed during induction of anesthesia with use of a validated anxiety
      measurement tool. Postoperatively, recall and recognition for picture cards seen
      during baseline testing and postintervention testing were assessed. RESULTS:
      Postoperatively, recall and recognition of pictures presented to patients after
      drug administration (anterograde amnesia) showed significant group differences (P
      = 0.0001), with recall impaired in the 10- (P = 0.004) and 20-min groups (P =
      0.0001). Similarly, recognition memory was impaired in the 5- (P = 0.0008), 10-
      (P = 0.0001) and 20-min (P = 0.0001) groups. Significant anxiolytic effects of
      midazolam were observed as early as 15 +/- 4 min after midazolam administration
      (P = 0.02). CONCLUSIONS: Midazolam administered orally produces significant
      anterograde amnesia when given as early as 10 min before a surgical procedure.

PMID- 10969301
TI  - Changes in regional myocardial function after coronary artery bypass graft
      surgery are predicted by intraoperative low-dose dobutamine echocardiography.
AB  - BACKGROUND: Left ventricular dysfunction is often reversed after coronary artery
      bypass graft (CABG) surgery; however, this change is not easily predicted. The
      authors hypothesized that functional changes after a low dose of dobutamine (5
      microgram. kg-1. min-1) intraoperatively would predict functional changes when
      complete revascularization was achieved. METHODS: The authors analyzed 560
      segments in 40 patients scheduled for elective CABG surgery for regional wall
      motion (1-5 scoring system) at four stages: baseline (after induction and
      intubation), with administration of low-dose dobutamine before cardiopulmonary
      bypass, after separation from cardiopulmonary bypass (early), and after
      administration of protamine (late). Two independent observers scored the
      myocardial regions according to a 16-segment model in multiple imaging planes.
      For each segment, the response to dobutamine was dichotomized as improved or not
      improved from baseline and analyzed with logistic regression. The influence of
      covariates (ejection fraction, myocardial infarction, diabetes mellitus, and beta
      blockers) was also determined with logistic regression models. P < 0.05 was
      considered significant. RESULTS: Changes in myocardial function after low-dose
      dobutamine were highly predictive for early (P < 0.0001) and late (P < 0.0001)
      changes in myocardial function from baseline regional scores. The overall odds
      ratio for early and late improvement increased by 20.7 and 34.6, respectively,
      when improvement was observed after low-dose dobutamine was administered. The
      overall positive predictive value of improved regional wall motion after CABG did
      not vary with left ventricular ejection fraction, a history of myocardial
      infarction, or beta blocker use, and it varied little with diabetic status
      (range, 0.86-0.96) if regional wall motion improved with low-dose dobutamine
      before CABG. The overall negative predictive value was 0.70; however, the range
      varied with diabetic status (i.e., lowest in diabetic patients and highest in
      nondiabetic patients). CONCLUSION: Intraoperative low-dose dobutamine is a
      reliable method to predict myocardial functional reserve and to determine
      functional recovery expected after coronary revascularization.

PMID- 10969302
TI  - Efficacy of preoxygenation with tidal volume breathing. Comparison of breathing
      systems.
AB  - BACKGROUND: Preoxygenation before tracheal intubation is intended to increase
      oxygen reserves and delay the onset of hypoxemia during apnea. Various systems
      are used for preoxygenation. Designed specifically for preoxygenation, the
      NasOral system uses a small nasal mask for inspiration and a mouthpiece for
      exhalation. One-way valves in the nasal mask and the mouthpiece ensure
      unidirectional flow. This investigation compares the efficacy of preoxygenation
      using the standard circle system with the NasOral system and five different
      resuscitation bags. METHODS: Twenty consenting, healthy volunteers were studied
      in the supine position for 5-min periods of tidal volume breathing using the
      circle absorber system, the NasOral system, and five resuscitation bags in a
      randomized order. Data were collected during room air breathing and at 30-s
      intervals during 5 min of oxygen administration. Inspired oxygen, end-tidal
      oxygen, and end-tidal nitrogen were measured by mass spectrometry. RESULTS: At 2.
      5 min of oxygenation, end-tidal oxygen plateaued at 88.1 +/- 4.8 and 89.3 +/-
      6.4% (mean +/- SD) for the circle absorber and NasOral systems, respectively.
      This was associated with inverse decreases in end-tidal nitrogen. At no time did
      these end-tidal oxygen or nitrogen values differ from each other. Three of the
      resuscitation bags (one disk type and two duck-bill type with one-way exhalation
      valves) delivered inspired oxygen more than 90%, and the end-tidal oxygen
      plateaued between 77 and 89% at 2 min of tidal volume breathing. The other two
      resuscitation bags (both duck-bill bags without exhalation valves) delivered
      inspired oxygen less than 40%, and the end-tidal oxygen values ranged between
      21.8 +/- 5.0 and 31.9 +/- 8.7%. CONCLUSIONS: The circle absorber and NasOral
      systems were equally effective in achieving maximal preoxygenation during tidal
      volume breathing. Resuscitation bags differed markedly in effectiveness during
      preoxygenation; those with duck-bill valves without one-way exhalation valves
      were the least effective. Thus, the use of these bags should be avoided for
      preoxygenation.

PMID- 10969303
TI  - Intracarotid infusion of the nitric oxide synthase inhibitor, L-NMMA, modestly
      decreases cerebral blood flow in human subjects.
AB  - BACKGROUND: The authors hypothesized that if nitric oxide (NO) was a determinant
      of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-L
      arginine (L-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood
      flow (CBF) and intracarotid L-arginine would reverse its effect. METHODS: In
      angiographically normal cerebral hemispheres, after the initial dose-escalation
      studies (protocol 1), the authors determined the effect of intracarotid L-NMMA
      (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol
      2). Changes in CBF and MAP were then determined at baseline, during L-NMMA
      infusion, and after L-NMMA during L-arginine infusion (protocol 3). To
      investigate effects of higher arterial blood concentrations of L-NMMA, changes in
      CBF and MAP were assessed at baseline and after a bolus dose of L-NMMA (250 mg/1
      min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min,
      protocol 4). CBF changes were also assessed during induced hypertension with
      intravenous phenylephrine (protocol 5). RESULTS: Infusion of L-NMMA (50 mg/min
      for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg;
      P < 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml. 100 g-1. min-1; P
      < 0.005) for 10 min. Intracarotid l-arginine infusion after L-NMMA (protocol 3)
      reversed the effect of L-NMMA. Bolus L-NMMA (protocol 4) increased MAP by 20% (80
      +/- 11 to 96+/-13 mmHg; P< 0.005), but there was no significant decrease in CBF.
      Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml. 100 g-1. min
      1; P< 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9
      to 95 +/- 6 mmHg; P = 0.001) but did not affect CBF. CONCLUSIONS: The results
      suggest that intracarotid L-NMMA modestly decreases CBF, and the background tone
      of cerebral resistance vessels may be relatively insensitive to NOS inhibition by
      the intraarterial route.

PMID- 10969304
TI  - Physostigmine reverses propofol-induced unconsciousness and attenuation of the
      auditory steady state response and bispectral index in human volunteers.
AB  - BACKGROUND: It is postulated that alteration of central cholinergic transmission
      plays an important role in the mechanism by which anesthetics produce
      unconsciousness. The authors investigated the effect of altering central
      cholinergic transmission, by physostigmine and scopolamine, on unconsciousness
      produced by propofol. METHODS: Propofol was administered to American Society of
      Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer
      controlled infusion pump at increasing concentrations until unconsciousness
      resulted (inability to respond to verbal commands, abolition of spontaneous
      movement). Central nervous system function was assessed by use of the Auditory
      Steady State Response (ASSR) and Bispectral Index (BIS) analysis of
      electrooculogram. During continuous administration of propofol, reversal of
      unconsciousness produced by physostigmine (28 microgram/kg) and block of this
      reversal by scopolamine (8.6 microgram/kg) were evaluated. RESULTS: Propofol
      produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD)
      microgram/ml (n = 17). Unconsciousness was associated with reductions in ASSR
      (0.10 +/- 0.08 microV [awake baseline 0.32 +/- 0.18 microV], P < 0.001) and BIS
      (55.7 +/- 8.8 [awake baseline 92.4 +/- 3.9], P < 0.001). Physostigmine restored
      consciousness in 9 of 11 subjects, with concomitant increases in ASSR (0.38 +/-
      0.17 microV, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6)
      scopolamine blocked the physostigmine-induced reversal of unconsciousness and the
      increase of the ASSR and BIS (ASSR and BIS during propofol-induced
      unconsciousness: 0.09 +/- 0.09 microV and 58.2 +/- 7.5, respectively; ASSR and
      BIS after physostigmine administration: 0.08 +/- 0.06 microV and 56.8 +/- 6.7,
      respectively, NS). CONCLUSIONS: These findings suggest that the unconsciousness
      produced by propofol is mediated at least in part via interruption of central
      cholinergic muscarinic transmission.

PMID- 10969305
TI  - Diagnosing sensory abnormalities with either normal values or values from
      contralateral skin: comparison of two approaches in complex regional pain
      syndrome I.
AB  - BACKGROUND: To diagnose sensory abnormalities, patient values can be compared
      with values of the general population (absolute approach) or to values measured
      at contralateral homologous skin (relative approach). The current study gives
      normal values for both approaches and compares the advantages of each method by
      applying the technique to patients with complex regional pain syndrome type I
      (CRPS I). METHODS: In 50 healthy control subjects, sensory and pain thresholds
      were measured for pressure, warmth, and cold on both wrists and both feet. In 53
      patients with unilateral CRPS I (33 hand, 20 foot), the same assessments were
      conducted twice, at an interval of 1 month. RESULTS: In control subjects,
      contralateral homologous sides have approximately the same sensitivity,
      supporting the validity of the relative approach in patients. Hypoesthesia and
      allodynia can be diagnosed by either the absolute or relative approach, whereas
      hyperesthesia and hypoalgesia can only be identified with the relative approach.
      The two approaches obtain different results in 20% of cases. Age, gender, and
      subject criteria may influence the absolute but not the relative approach. Both
      approaches are comparable with regard to reproducibility. Frequency distributions
      of sensory abnormalities in chronic CRPS I are presented. The most frequent
      diagnoses were cold allodynia and mechanical hypoesthesia and allodynia.
      CONCLUSIONS: To divide sensory characteristics into a binary classification of
      "normal" and "abnormal," the relative approach is the best choice, with the
      exception of cases in which the contralateral homologous side is absent or
      affected by disease. The authors recommend the relative approach for both
      research and clinical purposes.

PMID- 10969306
TI  - Sedation during spinal anesthesia.
AB  - BACKGROUND: Central neuraxial anesthesia has been reported to decrease the dose
      of both intravenous and inhalational anesthetics needed to reach a defined level
      of sedation. The mechanism behind this phenomenon is speculated to be decreased
      afferent stimulation of the reticular activating system. The authors performed a
      two-part study (nonrandomized pilot study and a subsequent randomized, double
      blind, placebo-controlled study) using the Bispectral Index (BIS) monitor to
      quantify the degree of sedation in unmedicated volunteers undergoing spinal
      anesthesia. METHODS: Twelve volunteers underwent BIS monitoring and observer
      sedation scoring (Observer's Assessment of Alertness/Sedation Scale [OAA/S])
      before and after spinal anesthesia with 50 mg hyperbaric lidocaine, 5%.
      Subsequently, 16 volunteers blinded to the study were randomized to receive
      spinal anesthesia with 50 mg hyperbaric lidocaine, 5% (n = 10) or placebo (n = 6)
      and underwent BIS and OAA/S monitoring. RESULTS: In part I, significant changes
      in BIS scores of the volunteers occurred progressively (P = 0.003). The greatest
      variations from baseline BIS measurement occurred at 30 and 70 min. In part II,
      there were significant decreases in OAA/S and self-sedation scores for patients
      receiving spinal anesthesia versuscontrol patients (P = 0.04 and 0. 01,
      respectively). The greatest decrease in OAA/S scores occurred at 60 min. BIS
      scores were similar between groups (P = 0.4). CONCLUSIONS: Spinal anesthesia is
      accompanied by significant sedation progressively when compared with controls as
      measured by OAA/S and self-sedation scores. This effect was not related to block
      height. The late sedation observed by OAA/S at 60 min may indicate a second
      mechanism of sedation, such as delayed rostral spread of local anesthetics. BIS
      was not a sensitive measure of the sedation associated with spinal anesthesia in
      the randomized, blinded portion of this study.

PMID- 10969307
TI  - Ceftriaxone pharmacokinetics during iatrogenic hydroxyethyl starch-induced
      hypoalbuminemia: a model to explore the effects of decreased protein binding
      capacity on highly bound drugs.
AB  - BACKGROUND: Although various drugs used by anesthesiologists highly bind to
      plasma proteins, the impact of iatrogenically induced hypoproteinemia on their
      pharmacologic effects has never been investigated. The authors determined the
      pharmacokinetics of ceftriaxone, a cephalosporin that binds strongly to albumin
      in postsurgical patients with hydroxyethyl starch-induced hypoalbuminemia.
      METHODS: Eleven hypoalbuminemic (serum albumin < 25 g/l) patients and age (+/- 5
      yr)-, sex-, and body surface area (+/- 10%)-matched healthy volunteers received a
      2-g ceftriaxone dose infused over a 15-min period. Fourteen venous blood samples
      were collected during the 24-h study period. Free ceftriaxone concentrations were
      determined by ultrafiltration. Antibiotic concentrations in plasma and
      ultrafiltrate were measured by ion-paired reversed-phase chromatography. The
      pharmacokinetic parameters derived from total and free antibiotic concentrations
      were determined using a noncompartmental method. Data are expressed as median and
      range. RESULTS: The pharmacokinetic parameters derived from total ceftriaxone
      concentrations were similar for the two groups, except for the median corrected
      volume of distribution at steady state, which was increased (P = 0.05) to 0.18
      l/kg (range, 0. 11-0.29 l/kg) in patients, compared with 0.15 l/kg (range, 0.13
      0.22 l/kg) in volunteers. The area under the free ceftriaxone concentration-time
      curve was twice as high in patients as in volunteers (median 192, range 114-301
      vs. median 122, range 84-169 h. mg-1. l-1;P = 0.03). Moreover, the free
      ceftriaxone concentration remained more than 4 mg/l during more time in patients
      (median, 16. 7; range, 12.6-21.4 vs. median, 11.1; range, 6.0-19.0 h; P = 0.03).
      CONCLUSIONS: Compared with healthy volunteers, patients with iatrogenic
      hypoalbuminemia have higher free ceftriaxone concentrations during the 24 h after
      antibiotic administration. This modification increases drug distribution into
      extravascular space and may enhance effectiveness.

PMID- 10969308
TI  - Potency of bupivacaine stereoisomers tested in vitro and in vivo: biochemical,
      electrophysiological, and neurobehavioral studies.
AB  - BACKGROUND: Chiral local anesthetics, such as ropivacaine and levobupivacaine,
      have the potential advantage over racemic mixtures in showing reduced toxic side
      effects. However, these S-(levo, or "-")isomers also have reportedly lower
      potency than their optical antipode, possibly resulting in no advantage in
      therapeutic index. Potency for local anesthetics inhibiting Na+ channels or
      action potentials depends on the pattern of membrane potential and so also does
      the stereopotency ratio. Here the authors have quantitated the stereopotencies of
      R-, S-, and racemic bupivacaine, comparing several in vitro assays of neuronal
      Na+ channels with those from in vivo functional nerve block, to establish
      relative potencies and to understand better the role of different modes of
      channel inhibition in overall functional anesthesia. METHODS: The binding of
      bupivacaine to Na+ channels was assessed indirectly by its antagonism of [3H]
      batrachotoxin binding to rat brain synaptosomes. Inhibition of Na+ currents by
      bupivacaine was directly assayed in voltage-clamped GH-3 neuroendocrine cells.
      Neurobehavioral functions were disrupted by bupivacaine percutaneously injected
      (0.1 ml; 0.0625-1.0%) at the rat sciatic nerve and semiquantitatively assayed.
      Concentration-dependent actions of R-, S-, and racemic bupivacaine were compared
      for their magnitude and duration of action. RESULTS: Competitive batrachotoxin
      displacement has a stereopotency ratio of R:S = 3:1. Inhibition of Na+ currents
      with different prepulse potentials shows that S > R potency when the membrane is
      hyperpolarized, and R > S potency when it is depolarized from normal resting
      values. Functional deficits assayed in vivo usually demonstrate no consistent
      enantioselectivity and only a modest stereopotency (R:S = 1.2-1.3) for peak
      analgesia achieved at the lowest doses. Other functions display no significant
      stereopotency in either the degree, the duration, or their product (area under
      the curve) at any dose. CONCLUSION: Although the in vitro actions of bupivacaine
      showed stereoselectivity ratios of 1.3-3:1 (R:S), in vivo nerve block at
      clinically used concentrations showed much smaller ratios for peak effect and no
      significant enantioselectivity for duration. A primary role for the blockade of
      resting rather than open or inactivated Na+ channels may explain the modest
      stereoselectivity in vivo, although stereoselective factors controlling local
      disposition cannot be ruled out. Levo-(S-)bupivacaine is effectively equipotent
      to R- or racemic bupivacaine in vivo for rat sciatic nerve block.

PMID- 10969309
TI  - Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and
      gadolinium: possible involvement of mitochondrial adenosine triphosphate
      sensitive potassium and stretch-activated channels.
AB  - BACKGROUND: Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP)
      channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated
      channels (blocked by gadolinium) have been involved in the mechanism of ischemic
      preconditioning. Isoflurane can reproduce the protection afforded by ischemic
      preconditioning. We sought to determine whether isoflurane-induced
      preconditioning may involve MKATP and stretch-activated channels. METHODS:
      Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed
      by 3 h of reperfusion. Before this, rabbits were randomized into one of six
      groups and underwent a treatment period consisting of either no intervention for
      40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal)
      followed by a 15-min washout period (isoflurane group; n = 9). The two groups
      received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or
      gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5
      hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5
      hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5
      hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct
      size were assessed by blue dye injection and tetrazolium chloride staining.
      RESULTS: Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27
      +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control,
      isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane
      gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/-
      20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone
      in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In
      contrast, infarct size in the isoflurane group was significantly reduced to 26 +/
      11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and
      gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/-
      21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium
      groups, respectively (P = nonsignificant vs.control). CONCLUSION: 5
      Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by
      isoflurane. This result suggests that MKATP channels and mechanogated channels
      are probably involved in this protective mechanism.

PMID- 10969310
TI  - Moxonidine, a selective imidazoline-alpha2 -adrenergic receptor agonist, produces
      spinal synergistic antihyperalgesia with morphine in nerve-injured mice.
AB  - BACKGROUND: Moxonidine, a novel imidazoline-alpha2-adrenergic receptor-selective
      analgesic, was recently identified as antinociceptive but has yet to be evaluated
      in neuropathic pain models. alpha2-adrenergic receptor-selective analgesics, and
      high-efficacy opioids, effectively inhibit neuropathic pain behaviors in rodents.
      In contrast, morphine potency and efficacy decreases in states of neuropathic
      pain, both in rodents and in humans, but may be restored or enhanced by
      coadministration of morphine with alpha2-adrenergic receptor-selective
      analgesics. The current experiments extend the evaluation of opioid-coadjuvant
      interactions in neuropathic subjects by testing the respective antihyperalgesic
      interactions of moxonidine and clonidine with morphine in a test of mechanical
      hyperalgesia. METHODS: Nerve-injured mice (Chung model) were spinally
      administered moxonidine, clonidine, morphine, and the combinations moxonidine
      morphine and clonidine-morphine. Hyperalgesia was detected by von Frey
      monofilament stimulation (3.3 mN) to the hind paws (plantar surface). The ED50
      values were calculated and the interactions tested by isobolographic analysis.
      RESULTS: In nerve-injured mice, moxonidine, clonidine, and morphine all dose
      dependently inhibited mechanical hyperalgesia. Furthermore, the combinations of
      moxonidine-morphine and clonidine-morphine resulted in substantial leftward
      shifts in the dose-response curves compared with those of each agonist
      administered separately. The calculated ED50 values of the dose-response curves
      of these combinations were significantly lower than their corresponding
      theoretical additive ED50 values. These results confirmed that both interactions
      were synergistic. CONCLUSIONS: Moxonidine and clonidine both synergize with
      morphine to inhibit paw withdrawal from nociceptive mechanical stimuli in nerve
      injured mice.

PMID- 10969311
TI  - Effects of thiopental and its optical isomers on nicotinic acetylcholine
      receptors.
AB  - BACKGROUND: With the exception of gamma-aminobutyric acidA (GABAA) receptors, the
      major molecular targets underlying the anesthetizing actions of thiopental have
      yet to be established. Neuronal nicotinic acetylcholine receptors (nAChRs) are
      closely related to GABAA receptors and hence might also be major targets. If so,
      they might be expected to be substantially inhibited by surgical concentrations
      (EC50 = 25 micrometer) of thiopental and to display the same stereoselectivity as
      does general anesthesia. METHODS: Neuronal alpha4beta2, neuronal alpha7 and
      muscle alphabetagammadelta nAChRs were expressed in Xenopus oocytes. Peak
      acetylcholine-activated currents were measured at -70 mV using the two-electrode
      voltage clamp technique. Racemic thiopental and its two optical isomers were
      applied with and without preincubation and at high and low concentrations of
      acetylcholine. RESULTS: Inhibition of all three nAChRs was enhanced by
      preincubation with thiopental, a protocol that mimics the pharmacologic situation
      in vivo. Using this protocol, inhibition was further enhanced by high
      concentrations of acetylcholine, with IC50 = 18 +/- 2, 34 +/- 4, and 20 +/- 2
      micrometer (mean +/- SEM) thiopental for the neuronal alpha4beta2, neuronal
      alpha7 and muscle alphabetagammadelta nAChRs, respectively, with Hill
      coefficients near unity. Neither the neuronal alpha7 nor the muscle
      alphabetagammadelta nAChR differentiated between the optical isomers of
      thiopental. However, R(+)-thiopental was significantly more effective than the S(
      ) isomer at inhibiting the neuronal alpha4beta2 nAChR; interestingly, this is
      diametrically opposite to their stereoselectivity for general anesthesia.
      CONCLUSIONS: Both central neuronal and peripheral muscle nAChRs can be
      substantially inhibited by thiopental at surgical EC50 concentrations but with
      either no stereoselectivity or one opposite to that for general anesthesia. Thus,
      nAChRs are probably not crucial targets for producing thiopental anesthesia,
      although nAChRs may play a part in the side effects produced by this agent.

PMID- 10969312
TI  - Comparative ventricular electrophysiologic effect of racemic bupivacaine,
      levobupivacaine, and ropivacaine on the isolated rabbit heart.
AB  - BACKGROUND: Numerous local anesthetics have an asymmetric tetrahedron carbon,
      which confers stereoselective differences between the isomers. The authors
      attempted to quantify the depressant effect of racemic bupivacaine,
      levobupivacaine, and ropivacaine on myocardial ventricular conduction and on
      myocardial contractility. METHODS: The authors studied the pharmacokinetics
      (outflow concentration) and pharmacodynamics (QRS widening) of the three drugs
      infused in an isolated rabbit heart preparation. All data were fitted
      simultaneously with use of mixed-effect modeling, thus allowing precise
      statistical comparison between the three drug parameters. The rate dependence of
      QRS widening was fitted separately. RESULTS: Racemic bupivacaine,
      levobupivacaine, and ropivacaine induced a calculated maximum increase in QRS
      duration in the ratio 1:0.4:0.3. Css50, the dose which caused half the maximum
      increase in QRS duration at steady state, was similar for all three drugs (22
      micrometer free concentration). A rate dependence of QRS widening was observed,
      which was in the ratio 1:0.5:0.25 for racemic bupivacaine, levobupivacaine, and
      ropivacaine, respectively. CONCLUSIONS: In the isolated rabbit heart, racemic
      bupivacaine, levobupivacaine, and ropivacaine induce an increase in QRS duration
      in the respective ratio of 1:0.4:0.3, which was rate dependent in approximately
      the same ratio.

PMID- 10969313
TI  - Cerebral histopathology following portal venous infusion of bacteria in a chronic
      porcine model.
AB  - BACKGROUND: The aim of this study was to histologically investigate brain damage
      after prolonged periods of bacteremia in pigs. METHODS: Twenty-one pathogen-free
      Gottingen minipigs were anesthetized and instrumented with a femoral arterial, a
      pulmonary arterial, and through midline abdominal incision with a portal venous
      catheter. After craniotomy the superior sagittal sinus was cannulated. A
      lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid.
      Twelve hours after instrumentation, the animals were randomized in two groups:
      septic and control animals. The septic group received an infusion of 107 colony
      forming units per kilogram of living Escherichia coli over 0.5 h through portal
      venous catheter each day. The control group received saline. Postoperative
      intensive care treatment included 4 days of controlled mechanical ventilation,
      sedation, and intravenous nutrition. The brains then were removed, fixed, and
      processed for histology. Each pathologic alteration found in the samples was
      assessed and given a severity code (0-3). RESULTS: Sham-operated animals showed
      no alterations caused by the instrumentation and the intensive care treatment.
      The septic group showed typical clinical signs of sepsis. Vasopressor support and
      mechanical ventilation prevented systemic hypotension and hypoxemia. High serum
      and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha
      were detected. The septic group showed severe histologic abnormalities of the
      brain including perivascular edema, spongiform degeneration, hyperemia, and
      purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken
      nuclei, and disintegration of the nuclear membrane. CONCLUSIONS: Abdominal sepsis
      induced severe brain damage that was not related to systemic hypoxia or ischemia.
      High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6
      were related to an inflammatory process in the brain resulting in cerebral edema
      and death of neurons.

PMID- 10969314
TI  - Differential effects of halothane and thiopental on surfactant protein C
      messenger RNA in vivo and in vitro in rats.
AB  - BACKGROUND: Pulmonary surfactant is a complex mixture of proteins and
      phospholipids synthetized by alveolar type II cells. Volatile anesthetics have
      been shown to reduce surfactant phospholipid biosynthesis by rat alveolar type II
      cells. Surfactant-associated protein C (SP-C) is critical for the alveolar
      surfactant functions. Our goal was to evaluate the effects of halothane and
      thiopental on SP-C messenger RNA (mRNA) expression in vitro in rat alveolar type
      II cells and in vivo in mechanically ventilated rats. METHODS: In vitro, freshly
      isolated alveolar type II cells were exposed to halothane during 4 h (1, 2, 4%)
      and 8 h (1%), and to thiopental during 4 h (10, 100 micrometer) and 8 h (100
      micrometer). In vivo, rats were anesthetized with intraperitoneal thiopental or
      inhaled 1% halothane and mechanically ventilated for 4 or 8 h. SP-C mRNA
      expression was evaluated by ribonuclease protection assay. RESULTS: In vitro, 4-h
      exposure of alveolar type II cells to thiopental 10 and 100 micrometer increased
      their SP-C mRNA content to 145 and 197%, respectively, of the control values. In
      alveolar type II cells exposed for 4 h to halothane 1, 2, and 4%, the SP-C mRNA
      content increased dose-dependently to 160, 235, and 275%, respectively, of the
      control values. In vivo, in mechanically ventilated rats, 4 h of halothane
      anesthesia decreased the lung SP-C mRNA content to 53% of the value obtained in
      control (nonanesthetized, nonventilated) animals; thiopental anesthesia increased
      to 150% the lung SP-C mRNA content. CONCLUSIONS: These findings indicate that
      halothane and thiopental used at clinically relevant concentrations modulate the
      pulmonary SP-C mRNA content in rats. In vivo, the additive role of mechanical
      ventilation is suggested.

PMID- 10969315
TI  - Cardiac troponin I and myocardial contusion in the rabbit.
AB  - BACKGROUND: Patients with cardiac contusion have a high risk of cardiac
      complications during emergency anesthesia. Despite the progress in cardiac
      imaging, a biologic marker of myocardial damage such as cardiac troponin I
      remains useful and has been proposed in clinical practice. The relationship among
      histologic injury, left-ventricular function, and release of cardiac enzymes and
      cardiac troponin I has been investigated after a controlled myocardial contusion
      in a rabbit model. METHODS: A global trauma (two levels of energy: 250 and 350
      mJ) was produced on an isolated preparation of rabbit's heart, of which the
      temperature, perfusion flow, beating rate, and left-ventricular volume were kept
      constant. Left-ventricular pressure and its first derivative as a function of
      time were measured during a 60-min period after the blow; a timed collection of
      the effluent was made to assess creatine kinase, lactate dehydrogenase, and
      cardiac troponin I. At the end of the period, an anatomic score of the contusion
      was calculated by histologic examination of the hearts. RESULTS: Compared with a
      control group, the two levels of cardiac trauma resulted in a proportional
      anatomic injury significantly correlated with left-ventricular dysfunction
      (Delta%dP/dtmax = -16 +/- 12 and -36 +/- 20% at 3 min, mean +/- SD). Transient
      releases in cardiac markers after the lesser amount of trauma contrasted with a
      prolonged and biphasic release of cardiac troponin I after the greater amount.
      Peak cardiac troponin I level was correlated with anatomic injury (rho = 0.596,
      P= 0.001) and negatively correlated with left-ventricular dysfunction (r = 
      0.375, P= 0.04). CONCLUSION: Cardiac troponin I is a marker of anatomic and
      functional consequences of experimental cardiac trauma and may be a predictive
      indicator of early posttraumatic cardiac complications during the postoperative
      period.

PMID- 10969316
TI  - Stereospecific interaction of ketamine with nicotinic acetylcholine receptors in
      human sympathetic ganglion-like SH-SY5Y cells.
AB  - BACKGROUND: Surprising clinical evidence suggests a block of sympathetic
      transmission by ketamine. The action of ketamine on nicotinic acetylcholine
      receptors (nAChRs) in human ganglions is unknown. Because ganglionic transmission
      depends on nAChRs, such information may help to clarify whether ketamine impairs
      ganglionic transmission in men. Because racemic ketamine as well as S(+)-ketamine
      are used clinically, the authors investigated stereospecific effects on human
      ganglionic nAChRs. Stereospecific psychomimetic effects have been attributed to
      voltage-dependent Kv channel inhibition; therefore the effects on nAChRs were
      compared with those on Kv channels present in the same cells. METHODS: Whole-cell
      currents through nAChRs and K channels were measured in SH-SY5Y cells with the
      patch-clamp technique by application of acetylcholine (1 mm, nAChRs) or by a step
      depolarization from a holding potential of -80 mV to +40 mV (K channels).
      Electrolyte conditions were identical for both currents. RESULTS: Racemic
      ketamine and the isomers inhibited nAChRs and K channels in a concentration
      dependent and reversible manner. Racemic ketamine inhibited nAChRs and K
      channels, with the anesthetic concentration inducing the half-maximal effect
      being 1.4 and 300 micrometer, respectively. Only inhibition of the nAChRs was
      stereoselective. The half-maximal concentrations were 0.8 and 3.6 micrometer for
      S(+)- and R(-)-ketamine. The K channels were 350 and 70 times less sensitive to
      the effects of S(+)- and R(-)-ketamine. CONCLUSION: Ketamine at concentrations
      found during clinical anesthesia exerts stereospecific effects on human
      ganglionic nAChRs but not on voltage-dependent K channels. Our results support
      the view that ketamine impairs sympathetic ganglionic transmission. Nonspecific
      effects on voltage-dependent K channels may underlie psychomimetic side effects.

PMID- 10969317
TI  - Facilitated uptake of fentanyl, but not alfentanil, by human pulmonary
      endothelial cells.
AB  - BACKGROUND: Extensive pulmonary uptake of lipophilic basic amines, such as
      fentanyl, attenuates early blood drug concentrations after rapid intravenous
      administration. The basis of this phenomenon is poorly understood. The authors
      tested the hypothesis that fentanyl uptake into cultured human lung microvascular
      endothelial (HMVE-L) cells occurs by facilitated uptake in addition to passive
      diffusion. The authors compared fentanyl and alfentanil uptake with that of
      antipyrine, a diffusible marker of pulmonary tissue water. In addition, the
      authors determined the effect of verapamil, a nonspecific inhibitor of drug
      transport, and UIC2, a blocking antibody of the P-glycoprotein drug transporter,
      on the uptake of these drugs. METHODS: Human lung microvascular endothelial cells
      were incubated, with varying concentrations of antipyrine and fentanyl or
      alfentanil in the absence or presence of varying verapamil concentrations or of
      UIC2. Supernatants were collected and cells were rinsed and dissolved.
      Supernatant and cell-associated antipyrine, fentanyl, and alfentanil
      concentrations were measured. The data were fit to a model of cellular uptake
      that allowed for passive diffusion and facilitated uptake. RESULTS: Alfentanil
      uptake by HMVE-L cells was indistinguishable from that of antipyrine for the
      concentration ranges studied. In contrast, at low concentrations, fentanyl
      sequestration into HMVE-L cells was substantially greater than that of
      antipyrine. Facilitated fentanyl uptake was blocked by verapamil, but not by
      UIC2, in a concentration-dependent manner. CONCLUSIONS: The differential HMVE-L
      uptake of fentanyl and alfentanil is consistent with the observed differences in
      the pulmonary uptake of these drugs. This suggests that specific fentanyl uptake
      and sequestration by HMVE-L cells may be the mechanisms of its extensive
      pulmonary uptake.

PMID- 10969318
TI  - Desflurane induces only minor Ca2+ release from the sarcoplasmic reticulum of
      mammalian skeletal muscle.
AB  - BACKGROUND: Desflurane is a weaker trigger of malignant hyperthermia than is
      halothane. There are very few data of the pathophysiologic background of this
      observation. Therefore, the authors' aim was to investigate the direct effect of
      desflurane on calcium release in skinned skeletal muscle fibers. METHODS: For the
      measurements, single saponin-skinned muscle fiber preparations of BALB/c mice
      were used. For Ca2+ release experiments, liquid desflurane at 0.6 and 3.5 mm was
      applied to weakly calcium-buffered solutions with no added Ca2+. Desflurane was
      diluted in strongly Ca2+-buffered solutions, with [Ca2+] between 3.0 and 24.9
      micrometer for [Ca2+]-force relations. Force transients were transformed into
      Ca2+ transients based on the individual [Ca2+]-force relations. As controls, 30
      mm caffeine and equimolar sevoflurane were investigated in the same muscle
      fibers. RESULTS: At 3.5 mm, desflurane induced peak force transients of 8 +/- 4%
      (mean +/- SD) of maximal Ca2+-activated force (Tmax). These peak values were
      significantly smaller than those in the presence of 3.5 mm sevoflurane (24 +/-
      10% of Tmax, P < 0.05), and 4 or 5 times smaller than previously reported Ca2+
      release-induced force transients by equimolar halothane. Calculated peak Ca2+
      transients derived from force transients and induced by 3.5 and 0.6 mm desflurane
      were significantly smaller than those induced by 30 mm caffeine. The [Ca2+]-force
      relation was shifted by desflurane, resulting in a Ca2+-sensitizing effect. The
      maximal Ca2+-activated force was significantly increased by 0.6 mm desflurane in
      comparison with the control, with no added substance (P </= 0.05). CONCLUSION:
      Desflurane induces only slight Ca2+ release in skinned skeletal muscle fibers.

PMID- 10969319
TI  - Stereoselective loss of righting reflex in rats by isoflurane.
AB  - BACKGROUND: Although it is accepted widely that optically active intravenous
      general anesthetics produce stereoselective effects in animals, the situation
      regarding volatile agents is confused. Conventional studies with scarce
      isoflurane enantiomers have been limited to small numbers of animals and produced
      conflicting results. By injecting these volatile enantiomers intravenously,
      however, it is possible to study large numbers of animals and obtain reliable
      results that can help to identify the molecular targets for isoflurane. METHODS:
      Pure isoflurane enantiomers were administered intravenously to rats after
      solubilization in a lipid emulsion. The ability of each enantiomer to produce a
      loss of righting reflex was determined as a function of dose, and quantal dose
      response curves were constructed. In addition, sleep times were recorded with
      each enantiomer. Chiral gas chromatography was used to measure relative
      enantiomer concentrations in the brains of rats injected with racemic isoflurane.
      RESULTS: The S(+)-enantiomer was 40 +/- 8% more potent than the R(-)-enantiomer
      at producing a loss of righting reflex. The S(+)-enantiomer induced longer sleep
      times (by about 50%) than did the R(-)-enantiomer. Rats anesthetized by a dose of
      racemic isoflurane sufficient to achieve a half-maximal effect had essentially
      identical brain concentrations of the two enantiomers. CONCLUSIONS: The S(+)
      enantiomer of the general anesthetic isoflurane is significantly (P < 0.001) more
      potent than the R(-)-enantiomer at causing a loss of righting reflex in rats.
      This confirms the view that isoflurane acts by binding to chiral sites. The
      observed degree of stereoselectivity provides a useful guide for ascertaining
      from in vitro experiments which molecular targets are most likely to play major
      roles in the loss of righting reflex caused by isoflurane.

PMID- 10969320
TI  - Thoracic epidural anesthesia increases mucosal perfusion in ileum of rats.
AB  - BACKGROUND: Previous studies reported that thoracic epidural anesthesia (TEA)
      protected against a decrease in gastric intramucosal pH, suggesting that TEA
      increased gut mucosal perfusion. The current study examines the effects of TEA on
      ileal mucosa using intravital microscopy in anesthetized rats. METHODS: Nineteen
      rats were equipped with epidural catheters, with the tip placed at T7 through T9.
      Rats were anesthetized and mechanically ventilated. After midline abdominal
      incision, the ileum was prepared for intravital microscopy. Videomicroscopy on
      the ileal mucosa was performed before and after epidural infusion of 20
      microliter of bupivacaine 0.4% (TEA group, n = 11 rats) or normal saline (control
      group, n = 8 rats). Microvascular blood flow in ileum mucosa was assessed offline
      using computerized image analysis. RESULTS: Control rats exhibited unchanged mean
      arterial pressure and microvascular perfusion. During TEA, mean arterial pressure
      was decreased compared with the control group (93 +/- 10 vs. 105 +/- 9 mmHg; P <
      0.05). Epidural bupivacaine increased red cell velocity in terminal arterioles
      from 888 +/- 202 to 1,215 +/- 268 micrometer/s (control, 793 +/- 250 to 741 +/-
      195 micrometer/s; P < 0.001 between groups). Because arteriolar diameter was not
      affected, this increase in red cell velocity may represent an increase in
      arteriolar blood flow. Total intercapillary area (inversely related to perfused
      capillary density) was unchanged, but for the TEA group the difference between
      total intercapillary area and the intercapillary area calculated for continuously
      perfused capillaries was decreased compared with the control group (16 +/- 12 vs.
      40 +/- 19%; P < 0.001), indicating a decrease in intermittent (stop-and-go) blood
      flow in the villus microcirculation. CONCLUSION: Thoracic epidural anesthesia
      increased gut mucosal blood flow and reduced intermittent flow in the villus
      microcirculation in the presence of a decreased perfusion pressure.

PMID- 10969321
TI  - Financial impact if payers use medicare rates: anesthesiology versus other
      specialties.
AB  - BACKGROUND: In 1992, Medicare changed its method for calculating physician
      payments. The resulting fee schedules have contained low payments for
      anesthesiologists. Now, other third-party (insurance) payers are using these
      schedules. The financial impact on anesthesiologists if all payers pay Medicare
      rates is unknown. METHODS: Payments from Medicare were compared with payments
      from other third parties in each clinical procedural terminology (CPT) grouping
      used by the West Virginia University Department of Anesthesiology during 1998.
      Changes in total Department of Anesthesiology receipts were determined if non
      Medicare third-party payers paid Medicare rates. Then, the effect of adding
      payments at Medicare rates from patients without insurance was determined.
      Finally, potential changes in receipts of the Departments of Anesthesiology,
      Radiology, Surgery, and Medicine were compared by considering only patients with
      insurance and recalculating total payments to the departments using Medicare
      rates. RESULTS: Medicare paid less than other third-party payers in every
      clinical procedural terminology group. Total Department of Anesthesiology
      payments would decrease by 31% if all non-Medicare third-parties paid Medicare
      rates. Adding payments at Medicare rates from patients without insurance still
      leads to a 21% decrease in total Department of Anesthesiology receipts.
      Considering only patients with third-party coverage, Medicare-rate payments would
      decrease total Department of Anesthesiology payments by 37%, whereas radiology,
      surgery, and medicine payments would decrease by 26, 22, and 13% respectively.
      CONCLUSIONS: Universal payments at Medicare rates would substantially reduce
      revenue to anesthesiologists, proportionally more than to radiologists, surgeons,
      or internists.

PMID- 10969322
TI  - Local anesthetics and the inflammatory response: a new therapeutic indication?

PMID- 10969323
TI  - Monitoring depth of anesthesia: with emphasis on the application of the
      bispectral index and the middle latency auditory evoked response to the
      prevention of recall.

PMID- 10969324
TI  - Sulfhemoglobinemia presenting as pulse oximetry desaturation.

PMID- 10969325
TI  - Neuropathic pain following cervical epidural steroid injection.

PMID- 10969326
TI  - Pulmonary hemorrhage associated with negative-pressure pulmonary edema.

PMID- 10969327
TI  - Original method for in situ repair of damage to endotracheal tube.

PMID- 10969328
TI  - Fatal barotrauma resulting from misuse of a resuscitation bag.

PMID- 10969329
TI  - Paradoxical vocal cord adduction.

PMID- 10969330
TI  - The meningeal permeability of R- and S-bupivacaine are not different: evidence
      that pharmacodynamic differences between the enantiomers are not the result of
      differences in bioavailability.

PMID- 10969331
TI  - Monitoring end-tidal ethanol concentrations during general anesthesia.

PMID- 10969332
TI  - P-V approach revisited.

PMID- 10969333
TI  - Extreme pulmonary hypertension and anesthesia induction.

PMID- 10969335
TI  - Dantrolene in malignant hyperthermia (MH)-susceptible patients with exaggerated
      exercise stress.

PMID- 10969334
TI  - Tubular fiberoptic laryngoscope (WuScope) and lingual tonsil airway obstruction.

PMID- 10969336
TI  - Use of a condom as a blade cover for laryngoscope.

PMID- 10969337
TI  - Fiberoptic laryngoscopy (WuScope) for double-lumen endobronchial tube placement
      in two difficult-intubation patients.

PMID- 10969338
TI  - Intraoral separation of a reinforced endotracheal tube.

PMID- 10969339
TI  - Insertion of a Fogarty catheter through an endotracheal tube for one-lung
      ventilation: a new method.

PMID- 10969340
TI  - Glottic adduction during hiccups in the presence of a cuffed endotracheal tube.

PMID- 10969341
TI  - A novel technique for conversion of nasotracheal tube to orotracheal.

PMID- 10969342
TI  - Rapid communication: development of in vitro resistance to macrophage-tropic- and
      T-cell-line-adapted HIV-1 strains among HIV-positive volunteers treated with
      highly active antiretroviral therapy.
AB  - We have described a peripheral blood mononuclear cell (PBMC) culture system in
      which control of endogenous virus and resistance to exogenous HIV-1 correlates
      with low viremia among HIV-1-positive people. Nineteen patients remained
      consistently resistant or susceptible for more than 5 years of follow-up. On the
      fifth year, 5 consistently susceptible volunteers with high viral loads began
      receiving highly active anti-retroviral therapy (HAART). After >6 months on
      HAART, 5 of 5 became completely or predominantly resistant on four visits over
      the next 6 months. Among HIV-1-positive donors, we had never observed reversal of
      PBMC phenotype from consistently susceptible to consistently resistant.
      Resistance correlated with suppression of plasma viremia and rebound in CD4+ T
      cell counts and percentages. When resistant PBMCs were challenged after CD8+ T
      cell depletion, 38 of 41 and 40 of 59 cultures became susceptible to HIV-1MN and
      HIV-1BaL, respectively. After combined CD8+ T-cell depletion and antibody
      neutralization of beta-chemokines, 16 of 18 cultures became susceptible to HIV
      1BaL. Overall, the finding that >90% of these cultures depleted of relevant
      antiviral effector arms could become infected indicates resistance was not due to
      residual antiretroviral drug metabolites in vitro. For 2 volunteers who
      discontinued therapy because of side effects, pretreatment viral load correlated
      with loss of in vitro resistance and viral rebound. In addition to resistance to
      laboratory strains of HIV-1, all patients developed resistance to at least one of
      two CCR5-tropic, clade B primary isolates: HIV-1P15 and HIV-1P27.

PMID- 10969343
TI  - Polymerase chain reaction-based assay for antibody-mediated neutralization of HIV
      1 reveals a population of nonneutralized virus undetected by conventional p24
      assay.
AB  - To be successful with strategies involving passive immunization or the generation
      of neutralizing antibodies against HIV, it is crucial that we improve our
      understanding of the process of antibody-mediated HIV neutralization. We have
      used a neutralization assay based on polymerase chain reaction (PCR) that is more
      rapid and sensitive than the conventional p24 neutralization assay based on
      enzyme-linked immunosorbent assay (ELISA). PCR assays permit measurement of the
      number of infectious events and can detect small amounts of HIV-1 only a few days
      postinfection. In these studies, the human anti-V3 monoclonal antibody 694/98-D
      was used to neutralize the infectivity of the laboratory isolate HIVIIIB for CEM
      SS cells. 8E5/LAV cells, which contain a single integrated copy of proviral DNA
      per cell, served as a standard to determine the amount of HIV-1 copies in
      infected CEM-SS cells. Evaluation of antibody-mediated neutralization was
      possible at 2 to 3 days postinfection, at a time when p24 readouts were not
      conclusive. We achieved >95% neutralization of HIVIIIB, and of its molecular
      clone HXB2, using the monoclonal antibody 694/98-D. This degree of neutralization
      is probably highly significant in vivo. Nevertheless, a small amount of both
      HIVIIIB and HXB2 ( approximately 5%) escapes neutralization and can consistently
      be detected after a few days by this sensitive assay. Experiments with different
      anti-HIV monoclonal antibodies and viruses showed that the assay could be applied
      to anti-V3 as well as anti-CD4 binding domain antibodies as well as HIV
      laboratory strains or primary isolates.

PMID- 10969344
TI  - Mortality for liver disease in patients with HIV infection: a cohort study.
AB  - We undertook this study to assess the association between the various potential
      causes of liver disease in HIV-seropositive patients and mortality due to liver
      failure. Three hundred and eight in-hospital deaths were observed from 1987 to
      December 1995 in a prospectively followed cohort of 1894 HIV-seropositive
      patients. For each study subject, clinical data were evaluated to assess whether
      liver failure had substantially contributed to mortality. A case control study
      nested in the cohort was then performed, which compared demographic and clinical
      variables observed at enrollment and during follow-up between patients who died
      for liver disease as the main or concurrent cause of death (cases) and those who
      died as a result of illness related to AIDS or other causes (controls). Among 308
      in-hospital deaths, liver failure was found the cause of death in 35 patients
      (12%); in 16 cases, it was the primary cause and in 19 cases it was concurrent.
      Multivariate analysis showed that in-hospital liver-disease-related mortality was
      independently associated with hepatitis B surface antigen reactivity (odds ratio
      [OR], 9; 95% confidence interval [CI], 3.8-21.7) and history of alcohol abuse
      (OR, 2.3; 95% CI, 1-5.2). Prevention and treatment of hepatitis B virus infection
      and alcohol intake are management priorities in HIV-seropositive patients.

PMID- 10969345
TI  - Association of race and gender with HIV-1 RNA levels and immunologic progression.
AB  - CONTEXT: HIV-1 RNA and lymphocyte subset levels are the principal indications for
      antiretroviral treatment. Past reports have differed with regard to the effect of
      gender and race on these measures and in measures of disease progression.
      OBJECTIVE: To assess racial and gender differences in HIV-1 RNA levels and CD4+
      lymphocyte decline. DESIGN: A longitudinal study based in the two largest HIV
      natural history cohort studies conducted in 7 metropolitan areas of the United
      States. RESULTS: In all, 1256 adult women and 1603 adult men for whom multiple
      data points were available prior to initiation of antiretroviral therapy were
      included. Women were more likely to be nonwhite, to have a history of injection
      drug use, and to have HIV-associated symptoms. After adjustment for differences
      in measurement method, baseline CD4+ cell count, age, and clinical symptoms, HIV
      1 RNA levels were 32% to 50% lower in women than in men at CD4+ counts >200
      cells/mm3 (p <.001) but not at CD4+ cell counts <200 cells/mm3. HIV-1 RNA levels
      were also 41% lower in nonwhites than in whites (p <.001) and 21% lower in
      persons reporting a prior history of injection drug use (p <.001). Women had more
      rapid declines in CD4+ cell counts over time than men (difference in slope of 46
      cells/year) and nonwhite individuals had slower decline in CD4 cell counts than
      whites (difference of 39 cells/year). CONCLUSIONS: Both race and gender influence
      the values of HIV-1 RNA and the rate of HIV-1 disease progression as indicated by
      decline in CD4 cell counts over time. These effects could provide clues regarding
      the factors that influence HIV-disease progression and may indicate that
      guidelines for therapy should be adjusted for demographic characteristics.

PMID- 10969346
TI  - Economic evaluation of drug resistance genotyping for the adaptation of treatment
      in HIV-infected patients in the VIRADAPT study.
AB  - BACKGROUND: Costs of antiretroviral therapy for HIV-infected patients have
      increased at a time when most countries are attempting to contain health care
      costs. Part of this increase results from HIV drug resistance associated with
      virologic failure and a subsequent shift to more complex and costly therapies.
      Genotypic guided treatment is associated with better virologic outcome. However,
      it is not yet known whether it will be cost effective. METHODS: We present here
      an economic evaluation based on the results from the VIRADAPT study, a
      prospective, open-label, randomized trial comparing patients assigned to standard
      of care (n = 43), versus genotypic guided treatment (n = 64) for 6 months. Total
      follow-up for the extended trial was 1 year. Costs were computed from the
      viewpoint of the health care system. Hospitalization data were retrieved from the
      VIRADAPT study case report forms, costs were estimated from the cost of the
      corresponding diagnosis-related groups derived from the French national cost data
      base: these were actual costs and not charges. Data on the volume of tests
      prescribed, drugs, and clinic visits were retrieved from the VIRADAPT study
      database. The unit costs of tests and clinic visits were determined using the
      French national Social Security reimbursement price; costing of drugs used were
      based upon purchase price by either retail pharmacies or hospitals. Genotyping
      using TruGene HIV-1 assay was estimated at $500 per test from manufacturer's data
      (all figures in this paper are expressed in U.S. dollars). RESULTS: Total mean
      (standard deviation) yearly costs per patients were $20,412 (+/-$10, 129) in the
      standard of care group and $18,484 (+/-$9,652) in the genotyping group (p =.35).
      Drug costs represented 55% of total costs. There was a trend toward a decrease in
      drug costs in the genotyping arm (p =.07), the greatest reduction being in the
      decreased use of protease inhibitors in the genotyping arm. The additional
      expense of genotyping appeared to be offset by the savings obtained in drug
      costs. CONCLUSION: In our study, the cost of drug resistance testing is offset by
      a reduced use of protease inhibitors and their attendant costs. Although not
      reaching statistical significance, this trend in the reduction of drug costs and
      drug use presents a great interest for future trials.

PMID- 10969347
TI  - Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a
      multicenter cohort of HIV-1-infected Italian patients with virologic failure.
AB  - We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT
      region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV
      1 variants in 177 patients who failed to respond to combination therapy. Patients
      had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase
      inhibitors (NNRTIs) after a long-term experience with nucleoside reverse
      transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177
      patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had
      the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the
      pivotal Q151M substitution were detected in as many as 3.9% of the patients. One
      patient exhibited a 69S [VG] insert that has not been previously phenotypically
      characterized. This HIV-1 isolate had high levels of resistance to all NRTIs
      except stavudine. MddNR is an emerging problem after sequential therapy with this
      class of compounds among HIV-1-infected patients. Either didanosine (ddI) or
      zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing
      Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various
      NRTI combinations were the common background in the patients with the 69 insert.
      The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed
      in several other European countries (3.4%-6.5%). These data suggest that patients
      failed by NRTI regimens should be analyzed for the presence of both patterns of
      MddNR.

PMID- 10969348
TI  - Interaction of methadone with didanosine and stavudine.
AB  - For opiate-dependent injection drug users infected with HIV, methadone therapy
      may facilitate adherence to complex highly active antiretroviral therapy (HAART)
      regimens. Current HAART regimens include one or more nucleoside analogues. We
      investigated the effects of methadone on the pharmacokinetics of the tablet
      formulation of didanosine (ddI) and of stavudine (d4T) in 17 study subjects on
      stable methadone therapy and in 10 untreated controls. Methadone treatment
      reduced the measured areas under the time-concentration curve (AUC0-6) by 63% for
      ddI (p =.04) and by 25% for d4T (p =.005) and the extrapolated AUCs for the full
      dosing interval (AUC0-12) by 57% for ddI (p =.11) and by 23% for d4T (p =. 02).
      Peak drug concentrations (Cmax) were reduced by 66% (p =.007) and 44% (p =.001)
      for ddI and d4T, respectively. The effects on AUC and Cmax appeared to result
      primarily from decreases in bioavailability. Methadone also delayed drug
      absorption. Trough levels for methadone did not differ significantly from those
      in historical controls, suggesting that ddI and d4T did not substantially alter
      methadone disposition. The results suggest that larger doses of the tablet
      formulation or an alternate formulation may be needed when didanosine is given to
      study subjects treated with methadone.

PMID- 10969349
TI  - Prenatal zidovudine use and congenital anomalies in a medicaid population.
AB  - OBJECTIVES: To examine the association of prescribed zidovudine (ZDV) during
      pregnancy with congenital anomalies in a population-based cohort. METHODS:
      Medicaid claims were used to assess prescribed ZDV and children's major
      congenital anomalies in 1932 liveborn deliveries from 1993 to 1996 to HIV
      infected women in the state of New York (NYS), U.S.A. Prevalence of anomalies in
      the cohort was compared with that of a general NYS population. Within the cohort,
      adjusted odds of any anomaly were compared by receipt of ZDV and by trimester of
      first prescription. RESULTS: The adjusted prevalence of any anomaly in the study
      cohort was 2.76 times greater than in the general population (95% confidence
      interval [CI], 2.36-3. 17). Children of study women who were prescribed ZDV had
      increased adjusted odds of any anomaly (adjusted odds ratio [OR], 1.55; 95% CI,
      1.01-2.29). Adjusted ORs (with CIs) by trimester of first prescription were 1.20
      (0.58-2.51), 1.47 (0.85-2.55), and 1.84 (1. 04-3.25) for the first, second, and
      third trimesters, respectively. CONCLUSION: Children of HIV-infected women in
      this cohort had a greater prevalence of major anomalies than did the general NYS
      population. An increased risk of major anomalies was not evident for first
      trimester exposure when the association would have been most biologically
      plausible.

PMID- 10969350
TI  - Lower HIV-2 plasma viral loads may explain differences between the natural
      histories of HIV-1 and HIV-2 infections.
AB  - To explain the low transmissibility and pathogenicity of HIV-2 infection's plasma
      viral loads in both HIV-1- and HIV-2-infected persons were compared by using the
      polymerase chain reaction (PCR)-based Amp-RT assay to measure levels of reverse
      transcriptase (RT) activity. The study comprised a total of 155 HIV-infected
      people including 58 who were infected with HIV-2 with CD4+ cell counts <500 x
      106/L (n = 15), CD4+ cell counts >500 x 106/L (n = 26), or with tuberculosis (TB;
      n = 17), and 97 HIV-1-infected people with CD4+ cell counts <500 x 106/L (n =
      32), CD4+ cell counts >500 x 106/L (n = 25), or TB (n = 40). Among persons with
      CD4+ cell counts <500 x 106/L, 11 (73.3%) of 15 HIV-2-infected persons had
      detectable plasma RT activity compared with 25 (78.1%) of 32 HIV-1-infected
      persons (p =.725). However, the median HIV-2 plasma RT activity in this group was
      significantly lower (2561 x 10-10 U/ml; p =.036; detectable range, 1712-644,868 x
      10-10 U/ml) than the RT activity of HIV-1-infected persons with similar CD4+ cell
      counts (13,241 x 10-10 U/ml; detectable range, 8482-1,478,880 x 10-10 U/ml).
      Among TB patients, 10 (58.8%) of 17 HIV-2-infected persons had detectable plasma
      RT activity compared with 30 (75%) of 40 HIV-1-infected persons (p =.342). In
      contrast, among patients with CD4+ cell counts >500 x 106/L, none of 26 HIV-2
      infected persons had detectable RT activity compared with 13 (52%) of 25 HIV-1
      infected persons (p <.001). Our data suggest that unlike HIV-1 infection, HIV-2
      infections with CD4+ cell counts >500 x 106/L are associated with a low level of
      viral replication, which may explain the longer clinical latency and lower
      transmissibility seen in HIV-2 infection.

PMID- 10969351
TI  - HIV-1-Specific CD4 helper function in persons with chronic HIV-1 infection on
      antiviral drug therapy as measured by ELISPOT after treatment with an
      inactivated, gp120-depleted HIV-1 in incomplete Freund's adjuvant.
AB  - OBJECTIVE: We hypothesized that treatment of HIV-1-seropositive study subjects
      receiving potent antiviral therapy with an HIV-specific immune-based therapy
      would increase HIV-1-specific T-helper immune function. DESIGN: 10 HIV-1
      seropositive study subjects receiving antiretroviral therapy were treated with an
      inactivated, gp120-depleted immunogen in IFA (HIV-1 immunogen, Remune) at
      baseline, week 12, and week 24. METHODS: The frequency of HIV-1 antigen
      stimulated interferon-gamma (IFN-gamma)-producing cells was determined by the
      ELISPOT assay. RESULTS: Study subjects significantly increased their frequency of
      HIV-1-stimulated (p <. 001) or p24 antigen-stimulated (p <.01) IFN-gamma
      producing cells after one, two, and three treatments of HIV-1 immunogen.
      Depletion of CD4 cells resulted in the strongest abrogation of the IFN-gamma
      response. The frequency of HIV-1 (r = 0.64; p =.0002) and p24 (r = 0. 72; p
      <.001) antigen-stimulated IFN-gamma-producing cells in the CD8-depleted
      population before and after treatment was associated with the lymphocyte
      proliferative response. CONCLUSIONS: Treatment with HIV-1 immunogen significantly
      enhanced the frequency of HIV-1-specific IFN-gamma-producing cells. Studies are
      ongoing to determine the relationship between this reversal of HIV-specific
      anergy and virologic outcomes.

PMID- 10969352
TI  - Incidence and trends in Kaposi's sarcoma in the era of effective antiretroviral
      therapy.
AB  - OBJECTIVE: To evaluate the impact of antiretroviral and antiherpesvirus therapies
      on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in
      a large multicenter HIV/AIDS surveillance system between 1990 and 1998. METHODS:
      Incidence was calculated per 100 person-years (py); the effects of therapies on
      risk for KS were calculated by using multivariate Poisson regression controlling
      for gender, race/ethnicity, age, HIV exposure mode, CD4+ cell count, and calendar
      year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple
      therapy (95% of triple therapy regimens contained a protease inhibitor).
      Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies
      evaluated. RESULTS: There were 37,303 HIV-infected people in the study
      contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50%
      reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with
      those who were not prescribed antiretroviral therapy and there was a reduction in
      risk for KS among persons prescribed foscarnet (p =.05). Overall, KS incidence
      declined an estimated 8.8% per year (observed incidence 4. 1 per 100 py in 1990
      to 0.7 per 100 py in 1998; p <.001). CONCLUSION: Incidence of KS is declining in
      this large U.S. population and may continue to decline as new, more effective
      antiretroviral agents are developed and used widely.

PMID- 10969353
TI  - Factors affecting African-American participation in AIDS research.
AB  - BACKGROUND: Although African Americans are disproportionately affected by the
      AIDS epidemic, they are underrepresented in AIDS research, particularly in AIDS
      clinical trials. This study examines a multidimensional construct of distrust and
      other factors that may affect willingness to participate in AIDS research.
      METHODS: A total of 301 African Americans (aged >/=18 years) in Durham, North
      Carolina participated in a cross-sectional survey. In-person interviews, 20 to 25
      minutes in length, were conducted with participants. Structural equation modeling
      was used to develop models exploring distrust and other factors affecting
      willingness to participate in AIDS research among African Americans. RESULTS:
      Distrust was the strongest inverse predictor of willingness to participate in
      AIDS clinical trials. Distrust was not significantly associated with willingness
      to participate in AIDS surveys and educational interventions. Altruism,
      facilitators/barriers, religiosity, and economic group membership were also
      significantly associated with willingness to participate in AIDS clinical trials.
      Only altruism was significantly associated with willingness to participate in
      AIDS surveys and educational interventions. CONCLUSIONS: Distrust about research
      institutions is a significant barrier to recruiting African Americans in AIDS
      clinical trials. Issues of distrust need to be acknowledged by researchers to
      develop better recruitment and retention strategies when conducting AIDS clinical
      trials in African-American communities.

PMID- 10969354
TI  - Age-dependent expression of the HIV-1 coreceptor CCR5 on CD4+ lymphocytes in
      children.

PMID- 10969356
TI  - Successful allogeneic bone marrow transplant in an HIV-1-positive man with
      chronic myelogenous leukemia.

PMID- 10969355
TI  - Preliminary experience of adverse drug reactions, tolerability, and efficacy of a
      once-daily regimen of antiretroviral combination therapy.

PMID- 10969357
TI  - Microsporidiosis and HIV.

PMID- 10969358
TI  - Serotype, parental country of birth, and ethnic status in unlinked anonymous
      neonatal HIV seroprevalence surveys.

PMID- 10969359
TI  - Surveillance of antiretroviral prescriptions.

PMID- 10969360
TI  - Intravenous equipment--infusions.

PMID- 10969361
TI  - Electronic publishing: value or threat?

PMID- 10969362
TI  - Tramadol--present and future.
AB  - The atypical opioid, tramadol, has recently been introduced into Australia and
      New Zealand. Tramadol's efficacy in a wide range of acute and chronic pain
      states, its multi-formulation availability, and its low serious side-effect
      potential at high doses and in prolonged therapy, combine to bestow on it a user
      friendly profile, for short- and long-term use in hospitals and communities. This
      paper reviews the following: its formulation and routes of administration; its
      unique enantiomeric biochemistry and metabolism; its triple mechanisms of action;
      its pharmacokinetics and pharmacodynamics; its analgesic efficacy compared with
      other opioids; the indications for its clinical use in a variety of acute and
      chronic (including cancer) painful states; its specific use in the elderly, in
      paediatric and in obstetric patients; its adverse event (including drug
      interaction) and safety profile; its advantages in terms of its relative lack of
      respiratory depression, major organ toxicity and histamine release, and
      dependence and abuse potential. The review looks at new uses for this drug and
      what can be expected in this area in the future.

PMID- 10969363
TI  - Potential use of pharmacological markers to quantitatively assess liver function
      during liver transplantation surgery.
AB  - Early functioning of the transplanted liver is of crucial importance to the
      recipient. This function may be assessed by measuring the disposition of
      substances that are mainly eliminated via the liver. None of the agents currently
      used is ideal for this purpose. Measurement of mono-ethyleneglycinexylidide
      (MEGX) formation from lignocaine is useful and has been widely used in liver
      transplantation to assess liver graft function. MEGX formation can be affected by
      the use of drugs that influence liver perfusion or interfere with the CYP450
      enzyme system. Indocyanine green clearance is a convenient method but both blood
      flow and hepatocellular function affect the test results. Tests of caffeine
      clearance, galactose elimination capacity and antipyrine clearance all require
      time-consuming, technically cumbersome and expensive serial blood sampling. The
      aminopyrine breath test is non-invasive, but gastric emptying and the patient's
      physical state affect results. The potential hazard of exposure to radioactive
      compounds limits the wide clinical use of both aminopyrine and erythromycin
      breath tests. Monitoring the rate of recovery from neuromuscular blockade induced
      by vecuronium and rocuronium can provide valuable information on liver function.

PMID- 10969364
TI  - Electroencephalographic indices related to hypnosis and amnesia during propofol
      anaesthesia for cardioversion.
AB  - Most previous studies which have assessed the depth of anaesthesia using the
      Bispectral Index (BIS) have used multi-agent anaesthetics with relatively slow
      induction and recovery times. Elevation of electroencephalographic (EEG)
      Beta/Alpha Ratio has been linked to onset of midazolam amnesia. Propofol
      anaesthesia for cardioversion in 19 patients enabled us to profile the changes in
      BIS and Beta/Alpha Ratio during a short, single-agent anaesthetic with a
      relatively rapid induction and recovery period. BIS values did not alter
      significantly through onset of amnesia and hypnosis as compared with awake
      values. Cardioversion occurred over a wide range of BIS values (38 to 94), with
      recovery at a median BIS value of 79. We observed the BIS to lag about 60 s
      behind the clinical situation (termed BIS60). The BIS60 more closely tracked the
      clinical level of consciousness, showing statistically significant differences
      from the uncorrected BIS. (amnesia (median BIS60 = 82, P = 0.02), hypnosis
      (median BIS60 = 67, P = 0.01), eye opening (median BIS60 = 90, P = 0.001)). An
      early EEG Beta/Alpha Ratio peak occurred at a mean of 4.6 s (SD = 16.6) after
      clinical amnesia onset and a late peak at a mean 58 s (SD = 144) after eye
      opening. There was no significant EEG response to cardioversion. We conclude
      that: (1) in rapidly changing conditions, the value of the BIS most accurately
      reflects the level of consciousness of the patient about 60 s in the past, and
      (2) the onset and offset of propofol-induced amnesia commonly corresponds to a
      peak in Beta/Alpha Ratio of the EEG.

PMID- 10969365
TI  - Pre-emptive analgesia with epidural morphine or morphine and bupivacaine.
AB  - Studies of preemptive analgesia in humans have shown conflicting results. The
      study design, patient population and the duration of assessment of postoperative
      pain are important in the evaluation of preemptive analgesia. We carried out a
      prospective, randomized, double-blind controlled study in 80 patients of physical
      status ASA 1-3 undergoing upper abdominal and thoracic surgery. Patients received
      two epidural injections, one 20 minutes before induction and the other at the end
      of surgery. Study solution was either morphine (50 micrograms/kg), with or
      without 0.1% bupivacaine in 10 ml of normal saline, or normal saline alone. The
      study groups (Pre M, Pre MB) were given either morphine or morphine-bupivacaine
      before induction and saline at the end of surgery. The control groups (Post M,
      Post MB) were given saline before induction and morphine or morphine-bupivacaine
      at the end of surgery. Postoperative pain was assessed with a Visual Analogue
      Scale (VAS) during coughing and deep breathing at six-hourly intervals for five
      days. Epidural morphine was given if the VAS exceeded 4. Pre MB compared to Post
      MB had a significantly increased interval between the analgesic top-ups (P <
      0.01) and decreased total postoperative morphine requirements (P < 0.0001) and
      number of top-ups (P < 0.001). Pre M and Post M were comparable. Pre MB compared
      to Pre M had significantly decreased total postoperative morphine requirements (P
      < 0.0001) and number of top-ups (P < 0.0001). Epidural morphine plus bupivacaine
      is effective as a preemptive analgesic. Morphine plus bupivacaine has better
      efficacy than morphine given alone before the induction of anaesthesia.

PMID- 10969366
TI  - Agreement between two plasma bicarbonate assays in critically ill patients.
AB  - Previous studies have suggested that measurement of plasma bicarbonate
      concentration using the Henderson-Hasselbalch equation may be unreliable,
      particularly in critically ill patients. We examined the agreement between two
      plasma bicarbonate concentration assays in critically ill patients. Data were
      collected from records of routine daily blood samples. Paired samples were taken
      at the same time from arterial lines. A Bland-Altman analysis was used to compare
      two bicarbonate assays in clinical use. The first used the Henderson-Hasselbalch
      equation for blood-gas machine calculations. The second used a spectrophotometric
      enzymatic technique. Comparing the enzymatic method to the calculated method
      (enzymatic minus calculated) the bias was -1.6 mmol/l (95% CI: -1.2 to -2.0
      mmol/l). The limits of agreement were -5.85 mmol/l to 2.65 mmol/l. This study
      found poor agreement between the two bicarbonate assays. This poor agreement is
      clinically important but the causes are unclear. We suggest further investigation
      of the reliability of bicarbonate assays.

PMID- 10969367
TI  - Effect of bolus dose of remifentanil on haemodynamic response to tracheal
      intubation.
AB  - A randomized placebo-controlled double-blinded study was conducted in 40 ASA 1
      and 2 patients to determine the dose response of remifentanil in attenuating the
      haemodynamic response to tracheal intubation. Patients were allocated to one of
      four groups: placebo, remifentanil 1 microgram.kg-1, remifentanil 2 micrograms.kg
      1 and remifentanil 4 micrograms.kg-1. A propofol target-controlled infusion was
      started at 4 micrograms.ml-1 and incrementally titrated to loss of verbal
      contact. Muscle relaxation was provided by cisatracurium. The study drug was
      given three minutes later over 30 seconds, and 90 seconds later the patient's
      trachea was intubated under direct laryngoscopy. Baseline noninvasive blood
      pressure and heart rate recordings were made prior to starting target-controlled
      infusion, then at one-minute intervals after loss of verbal contact for the
      duration of the study. Demographic data and target-controlled infusion rate at
      intubation was similar for the groups. Following intubation, heart rate increased
      by 15% in the placebo group, 10% in 1 microgram.kg-1 group, with no changes in 2
      micrograms.kg-1 and 4 micrograms.kg-1 groups. Systolic blood pressure following
      intubation increased by 30% in the placebo group, 10% in the 1 microgram.kg-1
      group and remained unchanged in the 2 micrograms.kg-1 and 4 micrograms.kg-1
      groups. Remifentanil 1 microgram.kg-1 attenuated the rise in heart rate and
      systolic blood pressure. Remifentanil 2 micrograms.kg-1 blocked the haemodynamic
      response completely: no further benefit was shown from increasing the dose to 4
      micrograms.kg-1.

PMID- 10969368
TI  - Postoperative sore throat and hoarseness following tracheal intubation using air
      or saline to inflate the cuff--a randomized controlled trial.
AB  - Sore throat and hoarseness following tracheal intubation is common. The aetiology
      may include high tracheal cuff pressures. We performed a double-blind, randomized
      controlled trial in 126 intubated patients to compare the incidence and severity
      of sore throat and hoarseness following inflation of the cuff using air or
      saline. Intra-cuff pressures were compared to assess any change due to inward
      diffusion of nitrous oxide. The incidence of significant sore throat and/or
      hoarseness overall was 15.0%. There was no statistically significant difference
      between the groups (air 15.9%, saline 14.5%). In the air group mean intra-cuff
      pressure increased significantly (start 14.0 mmHg, end 40.9 mmHg), while in the
      saline group there was no significant increase (start 12.7 mmHg, end 14.6 mmHg).
      The substitution of saline reliably results in sustained low intra-cuff pressures
      but high tracheal cuff pressure is not an important factor in the development of
      sore throat or hoarseness postoperatively within the pressure range and duration
      of operation studied.

PMID- 10969369
TI  - The intubating laryngeal mask airway: effect of handle elevation on efficacy of
      seal, fibreoptic position, blind intubation and airway protection.
AB  - We conducted three studies to test the hypothesis that elevation of the
      intubating laryngeal mask (ILM) handle increases efficacy of seal, changes
      fibreoptic position, prevents aspiration of regurgitated fluid and improves
      intubation. In study 1, the ILM was inserted into 20 paralysed, anaesthetized
      patients and 20 cadavers. Oropharyngeal leak pressure and fibreoptic position
      were measured at an intracuff pressure of 0, 60 and 120 cm H2O with 0, 20 and 40
      N of elevation force. In study 2, the oesophageal pressure at which regurgitation
      and aspiration occurred was measured in 20 cadavers with the ILM at the above
      intracuff pressures and elevation forces and 10 cadavers without the ILM
      (controls). In study 3, ease of blind intubation (first attempt only) was
      determined in 20 paralysed, anaesthetized patients at 0 and 40 N elevation force.
      In study 1, there was a significant increase in oropharyngeal leak pressure with
      increasing elevation force at an intracuff pressure of 0 and 60 cm H2O. There
      were no changes in fibreoptic position. Oropharyngeal leak pressure and
      fibreoptic position were similar between patients and cadavers. In study 2,
      oesophageal pressure for regurgitation and aspiration was usually greater for the
      ILM than controls (all: P < 0.05. Aspiration and regurgitation usually occurred
      at the same oesophageal pressure. In study 3, blind intubation was more
      successful at 0 N than 40 N (15/20 v 8/20, P = 0.03). We conclude that elevation
      of the ILM handle has little clinical utility other than as a temporary measure
      to improve the efficacy of the seal.

PMID- 10969370
TI  - Prediction of the mediastinal drainage after coronary artery bypass surgery.
AB  - Using multiple correlation and linear regression approaches, we investigated the
      association between the amount of mediastinal drainage for the first 24
      postoperative hours and clinical variables as well as multiple haematological
      tests performed at three time points: before anaesthesia induction, 10 minutes
      after protamine administration and just after skin closure, on 46 patients
      undergoing primary coronary artery bypass grafting. Three models from the three
      times were then developed to predict mediastinal drainage. The number of internal
      mammary grafts, the total number of grafts and plasma fibrinogen concentration
      were useful predictors of mediastinal drainage at all three times. The platelet
      count taken only after skin closure was found to provide additional predictive
      information. Each regression model explained approximately 60% of the variation
      in postoperative mediastinal drainage. The information obtained from these
      predictive models is useful in defining high-risk populations.

PMID- 10969371
TI  - Clinical evaluation of the non-invasive cardiac output (NICO) monitor in the
      intensive care unit.
AB  - The Non-invasive Cardiac Output (NICO) monitor (Novametrix Medical Systems Inc.,
      Wallingford, CT, U.S.A.) utilizes a minimally-invasive partial rebreathing method
      to determine cardiac output by means of a differential form of the Fick equation.
      We evaluated the NICO monitor by comparing its output to paired measurements
      obtained by the standard thermodilution (TD) technique in patients who had
      recently undergone cardiac surgery. Forty-two paired measurements were carried
      out in 12 patients. The correlation between the two methods was moderate with a
      correlation coefficient of 0.691. Repeated measures ANOVA showed that TD measures
      of cardiac output were significantly higher than those obtained by the NICO
      monitor (P = 0.0003). Comparison of the two techniques using the method described
      by Bland and Altman showed decreased correlation at higher values of cardiac
      output. We conclude that the NICO monitor may well have a place in intensive care
      monitoring, provided patients are not breathing spontaneously and are able to
      tolerate a 4 mmHg rise in PaCO2. It is less suitable for use in patients with a
      high cardiac output state.

PMID- 10969372
TI  - Recurrent laryngeal nerve blockade in patients undergoing carotid endarterectomy
      under cervical plexus block.
AB  - We report two cases of recurrent laryngeal nerve blockade arising during carotid
      endarterectomy under cervical plexus anaesthesia. These nerve blocks were thought
      to be due to the instillation of local anaesthetic. The nerve block in one
      patient was responsible for a paroxysm of coughing which caused the formation of
      a large neck haematoma. We believe this to be the first report of local
      anaesthetic induced recurrent laryngeal nerve blockade leading to such a
      complication.

PMID- 10969373
TI  - Leptospirosis complicated by severe aortic stenosis.
AB  - A previously well 62-year-old male from North Queensland presented with
      leptospirosis featuring fever, renal failure, hepatitis and pulmonary
      haemorrhage. Management was greatly complicated by severe and previously
      unrecognized aortic stenosis with a peak valve gradient of 125 mmHg. A successful
      outcome followed careful haemodynamic management and treatment of the infective
      illness with subsequent valve replacement.

PMID- 10969374
TI  - The treatment of tetanus with intrathecal baclofen.
AB  - The treatment of severe tetanus generally requires prolonged mechanical
      ventilation. We describe two cases managed with continuous intrathecal infusion
      of baclofen via a subcutaneous tunnelled spinal catheter and an abdominal
      injection port. Baclofen, by diminishing spasms and spasticity, allowed reduced
      sedation and paralysis requirements. This potentially decreases the time and
      resources required for intensive care management. Complications include sedation,
      hypotension and CSF infection. After appropriate dose adjustment, baclofen
      improves the management of severe tetanus.

PMID- 10969375
TI  - Tracheal foreign body following tube change during percutaneous dilational
      tracheostomy: a cautionary tale.
AB  - Although studies have shown percutaneous dilational tracheostomy to be a safe and
      cost-effective alternative to conventional surgical tracheostomy, there are
      inherent risks and complications. We report an incident occurring during
      percutaneous dilational tracheostomy using the Portex technique, in which a
      significant cuff leak occurring on insertion of the tracheostomy tube
      necessitated an immediate tube change. During this latter procedure, using a
      fresh Portex kit and guidewire, the guidewire introducer became dislodged from
      the guidewire assembly and inadvertently impacted in the trachea. Routine
      bronchoscopy identified the hazard and the foreign body was successfully removed
      via the bronchoscope with no adverse sequelae.

PMID- 10969376
TI  - Spinal anaesthesia in a patient with epidermolysis bullosa dystrophica.
AB  - An adult patient with epidermolysis bullosa dystrophica underwent uneventful
      spinal anaesthesia. Insertion of a Quincke spinal needle proved easier and
      produced less skin distortion than insertion of a pencil-point spinal needle.
      Taping of intravenous lines is an alternative to the more usually recommended
      approach of suturing.

PMID- 10969377
TI  - Swelling and cyanosis of the tongue associated with use of a laryngeal mask
      airway.
AB  - We present a case report of a patient who developed acute swelling of the tongue
      during anaesthesia using the laryngeal mask airway. The swelling was thought to
      be due to obstruction of the venous drainage of the tongue. This was associated
      with isolated cyanosis of the tongue and paraesthesia. The swelling and cyanosis
      of the tongue resolved rapidly after removal of the laryngeal mask airway. The
      patient suffered paraesthesia of the tip of the tongue that lasted for two weeks.

PMID- 10969378
TI  - Epidural abscess after spinal anaesthesia.

PMID- 10969379
TI  - Alexander Wood's observations on the action of opiates.

PMID- 10969380
TI  - Failure of vaporizer interlock mechanism.

PMID- 10969381
TI  - Postobstructive pulmonary oedema.

PMID- 10969382
TI  - Anterior spinal artery syndrome masked by epidural analgesia.

PMID- 10969383
TI  - [Minimally invasive heart surgery--challenge and prospects for anesthesia].

PMID- 10969384
TI  - [Nausea and vomiting after anesthesia: possibly not a "never ending story"?].

PMID- 10969385
TI  - [Special anesthesiologic features in minimally invasive heart surgery].
AB  - When heart-lung machines made extracorporeal circulation possible in the fifties,
      cardiac surgeons gained virtually unrestricted access to the resting, motionless
      heart. Valve repair and reconstruction, in particular, made great progress as a
      result of extracorporeal circulation. While the distinct advantages of
      extracorporeal circulation for cardiosurgery remain undisputed, awareness of the
      significant perioperative risks of extracorporeal circulation for the patient has
      been increasing in recent years. This has lead to an interest in alternative
      cardiosurgical techniques avoiding extracorporeal circulation. Inspired by
      minimally-invasive procedures in abdominal surgery, cardiosurgical instruments as
      well as surgical techniques of access to the heart and large thoracic vessels
      were systematically modified leading to today's minimally-invasive cardiosurgical
      procedures such as off-pump coronary artery bypass grafting on the beating heart.
      Similarly, in the field of cardiac valve repair, new cannulation techniques for
      instituting extracorporeal circulation make median sternotomy unnecessary. The
      developments described above have lead to the recent introduction of robot
      assisted techniques with or without extracorporeal circulation, which are
      expected to make possible in the near future the performance of the whole range
      of cardiosurgical procedures with minimal surgical trauma. The introduction of
      the new techniques has changed the intraoperative responsibilities of the
      anesthesiologist. The present article will therefore describe both the new
      surgical techniques as well as the new tasks required of the anesthesiologist, in
      particular with regard to cannulation and monitoring. Since a number of terms in
      minimally-invasive cardiosurgery are not precisely defined, a clear description
      of the various surgical techniques is also provided.

PMID- 10969386
TI  - [Time course of neuromuscular blockade after rocuronium. A comparison between
      women and men].
AB  - BACKGROUND: We studied 40 patients (20 female and 20 male) undergoing elective
      surgery under general anaesthesia to evaluate the effect of gender on the
      pharmacodynamics of rocuronium. METHODS: Using electromyography (EMG) we
      determined the maximal neuromuscular block and time course of action of 0.45
      mg/kg rocuronium (1.5 x ED95). RESULTS: Age and body mass index were comparable
      between females and males (38 (+/- 8) vs. 37 (+/- 10) years and 24.2 (+/- 2.9)
      vs. 25.2 (+/- 1.7) kg/m2. However, significant differences in weight and height
      were found between females and males (65.7 +/- 9.3 kg vs. 77.5 +/- 5.5 kg; p <
      0.01 and 178 +/- 6.8 cm vs. 164 +/- 6.7 cm; p < 0.01). Onset time was shorter in
      females (168 +/- 65 s vs. 211 +/- 56 s; p < 0.05). Maximal neuromuscular blockade
      after 0.45 mg/kg rocuronium was 94 (+/- 3) % in females and 89 (+/- 6) % in
      males; p < 0.01. Clinical duration was increased in females (23 +/- 5 min vs. 17
      +/- 5 min; p < 0.05), while the recovery index was comparable between both groups
      (9 +/- 4 min in females and 9 +/- 3 min in males; n.s.). CONCLUSION: Compared to
      men neuromuscular blockade after 0.45 mg/kg rocuronium was more pronounced in
      women. The onset time was shortened and the clinical duration increased in female
      patients.

PMID- 10969387
TI  - [Rating the perioperative period by patients. First evaluation of a new
      questionnaire].
AB  - OBJECTIVE: There is an increasing demand for internal clinical quality assurance.
      For this reason methods for the assessment of patients' satisfaction and
      postoperative symptoms and complaints are needed. This article describes a new
      questionnaire for the measurement of these aspects. METHODS: The questionnaire
      consists of two parts. Part 1 assesses the intensity of symptoms related to the
      postoperative periods "recovery room", "first hours on ward" and "current state".
      Part 2 measures patients' satisfaction with anesthesiological care, unspecific
      perioperative care and postoperative convalescence. 431 patients completed the
      questionnaire after an elective operation. RESULTS: Results demonstrate a
      plausible difference in patients' symptoms between the three postoperative
      periods. The difference between the remembered complaints in the "recovery room"
      and the "first hours on ward" is of small degree. Related to the period
      immediately after anesthesia, women describe a worse state of health than men.
      Male and female patients do not differ in their satisfaction with
      anesthesiological care. Older patients describe greater satisfaction with
      perioperative care than younger ones. There are only a few significant
      correlations between the intensity of symptoms in the "recovery room" and data
      from anesthesiological documentation. CONCLUSIONS: The new questionnaire is
      sensitive for the change of symptoms in the course of postoperative time.
      Considering the results, a modification of the questionnaire ist suggested. This
      instrument is to be used in a greater and representative sample of patients now.

PMID- 10969388
TI  - [Brachial plexus. Long lasting neurological deficit following interscalene
      blockade of the brachial plexus].
AB  - An interscalene block of the brachial plexus was combined with general
      anaesthesia for repair of a complex chronic lesion of the shoulder. The
      localisation of the plexus with electro-stimulation and the injection of
      Bupivacain 0.5% were accomplished easily and without painful sensations. 48 hours
      later the block was still partially present. Paraesthesia and a sensory and motor
      innervation deficit affected mainly the dorsal fascicle, but also areas
      innervated by the median and lateral fascicles. The deficit did not completely
      disappear for 18 month. The cause could have been due to direct traumatisation
      during blockade or operation, toxic action of the injected substance (Bupivacain
      0.5%, 30 ml), distension of the plexus, a cervical syndrome or an aseptic
      plexitis, although a definite determination is not possible. However, the pattern
      of the lesion and the lack of pain during localisation of the plexus and
      injection favour traumatisation during the acromioplasty.

PMID- 10969389
TI  - [Risk factors for nausea and vomiting after general anesthesia: fictions and
      facts].
AB  - Numerous factors have been claimed to influence postoperative nausea and vomiting
      (PONV). A critical review of the literature reveals, that strong evidence based
      on original double-blind, randomized, controlled trials or their meta-analyses is
      only available for very few risk factors. For most other factors, although
      mentioned in narrative reviews, there is insufficient evidence. Sufficient
      evidence on original data or meta-analyses is present for female gender, a
      history of PONV or motion sickness, non-smoking-status, young age, volatile
      anaesthetics, nitrous oxide and postoperative opioids. Factors with conflicting
      results are the menstrual cycle, hypnotics for induction, mask ventilation and
      nasogastric tube, the experience of the anaesthetist, muscle relaxants and their
      antagonists and laparoscopic procedures. Insufficient evidence is present for the
      other types of operation, psychological factors including anxiety and pain. No
      evidence due to lack of data applies to postoperative movement, hemodynamic
      stability, hypercarbia and acid-base-shifts. For adipositas++ there is not only a
      lack of evidence for an effect but evidence for a lack of effect based on several
      multivariate analyses. In conclusion, we have developed the following simplified
      view: PONV is mainly caused by opioids and volatile anaesthetics when applied to
      susceptible patients (females, non-smoker, positive history of previous
      sickness).

PMID- 10969390
TI  - [The historical development of intensive care in Germany. Contemporary views. 17.
      Review of intensive care medicine. Progress or frustration?].

PMID- 10969391
TI  - Introduction of the carbon dioxide absorption method with closed circle breathing
      into anesthesia practice.
AB  - The circle breathing CO2 absorption system for use during acetylene anesthesia
      was described by Carl Gauss in 1924/1925. The apparatus was manufactured by
      Dragerwerk of Lubeck. A considerable number of publications on the apparatus
      employing the closed circle method of CO2 absorption appeared in the medical
      press soon thereafter. Later apparatus models, also built by Dragerwerk, were
      adapted for nitrous oxide-oxygen-ether anesthesia and introduced into practice by
      Paul Sudeck and Helmut Schmidt. Information about all this was transmitted to
      America through the German medical press, including the Draeger-Hefte. American
      anesthesia machine manufacturers began to develop closed circle CO2 absorbers
      several years later. Claims that the circle breathing CO2 absorption method was
      introduced into anesthesia practice by Brian Sword are not valid.

PMID- 10969392
TI  - [Proxy decision in health questions and advance designations by patients. A
      practice-oriented review of the legal and ethical problems in treating the
      incompetent patient].
AB  - Except in emergencies, the medical treatment of incompetent patients also has to
      be based upon an informed consent between the physician and a legitimate legal
      representative (durable power of attorney). Consequently, the German
      'Betreuungsrecht' advices persons to designate in advance such a proxy or
      surrogate. However, an additional court-decision is demanded, if a medical
      measure poses significant risks for the future health or the life of the
      incompetent patient. On the base of the available epidemiologic data we
      illustrate that neither our medical nor our legal system could realistically cope
      with the practical consequences of this legislation: The vast majority of our
      present decisions in such cases is not covered by a legally valid informed
      consent, which implies possible forensic consequences. This article provides
      relevant clinical and legal advice on how to protect the legitimate interests of
      all concerned within the present framework, which should urgently be revised.

PMID- 10969393
TI  - [Medical rights review tables. Definitions, criteria, statutes, checklists for
      everyday clinical use].

PMID- 10969394
TI  - [Requirement for the structure and function of a nutritional support team].
AB  - Procedures in clinical nutrition have gained both invasiveness as well as the
      complexity. Thus improved education of professionals and their alliance in
      hospital based nutritional support teams (NST) is demanding. Two forms of
      collaboration, the "interdisciplinary nutritional committee" and the "department
      for nutritional therapy", are discussed. It is the goal of this contribution to
      present structure and tasks of an independently working department for
      nutritional support therapy. The pertinent areas of activity are composed as
      followed: clinical nutritional therapy, home nutrition, education, research, and
      quality management. The team members include the physician, the dietitian, the
      nurse, the nutritionist, and the pharmacist. The individual tasks as well as the
      areas of responsibility are presented. We discuss, whether nutritional support
      teams might be suitable to achieve cost reduction, provided adequate working
      conditions are available. Issues like "performance related reimbursement" and
      "NST certification" by health care organizations are discussed. We also elude to
      the option to merge services with other health care providers in order to built
      up an inter-disciplinary organization system. We conclude that nutritional
      support teams have to be prepared to meet hospital needs. Costs/benefit balances
      have to be assessable and must be documented. Although the effectiveness of
      selected nutritional support teams was clearly shown, it is the challenge of each
      individual team to produce proof of effectiveness for itself. Acceptable working
      conditions, however, should be provided as they have to be considered
      indispensable to achieve high quality performance.

PMID- 10969396
TI  - [In Process Citation]

PMID- 10969395
TI  - [Jet ventilation and anesthesia for diagnostic and therapeutic operations in the
      respiratory tract. Remarks on the paper of P. Biro and K. Weidemann, Anaesthesist
      (19999) 48:669-685].

PMID- 10969397
TI  - [Controlled hypotension].

PMID- 10969398
TI  - [The abdominal aortic aneurysm. Anesthesiologic considerations and perioperative
      management in conservative surgical treatment].

PMID- 10969399
TI  - [Laser therapy in dermatology and esthetic medicine. Side effects, complications
      and treatment errors].
AB  - Many different laser systems are used in dermatology. To wisely choose the
      correct laser for a given problem, one must be aware of both the spectrum of
      disorders for which each laser is suited and the potential side effects. We
      compare the side effect and complication profiles of the common laser systems
      pointing out their possibilities and limitations. Typical treatment errors will
      be pointed out. Dermatological training, extensive experience in laser therapy
      and compliance with quality guidelines are prerequisites for safe and successful
      treatment.

PMID- 10969400
TI  - [Actinic prurigo. An assessment of current status].
AB  - BACKGROUND AND OBJECTIVE: Actinic prurigo (AP) is a hereditary photodermatoses
      with typical symptoms and is quite common in North- and South-America. The key
      genetic factor appears to be a Native American background. In Europeans this type
      of AP is extremely rare; some dispute if this disease exists in Caucasians. Some
      newer publications postulate that these patients share HLA markers with the
      Native Americans. The most important differential diagnosis for AP is polymorphic
      light eruption which can be excluded relatively accurately by the clinical
      picture, typical histology and HLA pattern. PATIENTS/METHODS: The case of a
      female patient of Mayan ancestry living in Germany is presented. CONCLUSIONS:
      Since in literature sometimes cases from Europe are diagnosed as AP this is a
      problem of naming the disease. It would be helpful to integrate the terms
      hereditary or hereditaria into the name of the disease in indians.

PMID- 10969401
TI  - [Cutaneous angiosarcoma].
AB  - BACKGROUND AND OBJECTIVES: Angiosarcomas of the skin arise almost exclusively in
      the following clinical settings: 1. the face and scalp, usually in elderly
      individuals, 2. lymphedematous regions (lymphedema-associated angiosarcomas), and
      3. skin that has been previously irradiated (post-radiation angiosarcomas).
      Clinical and histopathologic diagnosis of angiosarcoma is difficult often
      resulting in great delay that obviates against early and possibly successful
      treatment of these very aggressive neoplasms. Diagnostic problems are described,
      and prognostic factors as well as the effect of different forms of treatment on
      the outcome are discussed. PATIENTS/METHODS: Retrospective study of 11 patients
      with cutaneous angiosarcomas. Clinical presentation, histopathology, therapy and
      survival time are analysed. RESULTS: Only 1 of 11 cases cutaneous angiosarcoma
      was clinically identified. Survival time was 1-24 months. Three patients who
      received radical surgery have not developed metastases and are still alive.
      CONCLUSIONS: Clinical and histopathologic diagnosis of cutaneous angiosarcomas is
      often very difficult. Prognosis is very bad; radical surgery seems to be the best
      therapeutical option.

PMID- 10969402
TI  - [Stabilizing the course of patients with stage IV advanced malignant melanoma by
      trofosfamide treatment].
AB  - BACKGROUND AND OBJECTIVE: Stage IV melanoma patients with progressive disease are
      a therapeutic challenge for every dermatologist. We wondered whether a mild oral
      chemotherapy with trofosfamide would ameliorate disease progression in these
      patients. PATIENTS/METHODS: 40 patients with melanoma (stage IV disease) were
      treated with 100 mg/day of trofosfamide for 6 months. All patients showed a
      progressive disease prior to this intervention. RESULTS: One patient experienced
      a partial remission, 25 patients showed a stable disease. Only 11 patients were
      progressive under trofosfamide treatment. 7 patients died during the study
      period. CONCLUSIONS: Therapy with trofosfamide seems to ameliorate disease
      progression in stage IV patients.

PMID- 10969404
TI  - [Illness-related stress in psoriasis vulgaris. Validation of the "Psoriasis Daily
      Stress Inventory"].
AB  - BACKGROUND AND OBJECTIVE: Illness specific stress plays an important part in the
      daily life of psoriatic patients. Until now for the measurement of relevant
      aspects of daily stress only the "Psoriasis Life Stress Inventory" (PLSI) of
      Gupta & Gupta exists; with the "Psoriasis-Alltagsstress-Inventar" (PAI), a German
      version of the PLSI is presented and its psychometric properties are discussed.
      PATIENTS/METHODS: 385 in-patients completed the PAI. The internal validity was
      examined by factor analysis. Moreover, the correlations between the PAI total
      score and sociodemographic parameters (ANOVA) and extent of skin involvement
      (multiple regression) were determined. RESULTS: The PLSI score proves to be
      sufficiently independent of age, sex, age at onset, and general extent of skin
      involvement. However, affections of the hands, the lower abdomen and the genitals
      show a strong influence on the total score. We found marked interrelations with
      the stigmatization feeling ("Questionnaire on Experience with Skin Complaints"
      QES, Schmid-Ott et al. 1998). CONCLUSIONS: The results suggest that the PAI is a
      useful and psychologically relevant questionnaire for psoriatic patients.

PMID- 10969403
TI  - [Lipoprotein and apolipoprotein electrophoresis in X-chromosome recessive
      ichthyosis].
AB  - BACKGROUND AND OBJECTIVE: The clinical differentiation of the hereditary
      ichthyosis forms is difficult and without laboratory markers hardly possible.
      Serum lipoprotein electrophoresis is one tool for detecting patients with
      recessive X-linked ichthyosis (XRI). Compared to controls, XRI patients show
      elevated electrophoretic mobilities of low density (LDL) and very low density
      lipoproteins (VLDL). This change in pattern is only partially explained by the
      increased LDL cholesterin sulfate concentration and is the subject of this study.
      PATIENTS/METHODS: Patients suffering from XRI and ichthyosis vulgaris, healthy
      controls. SDS-PAGE-electrophoresis and isoelectric focusing for detection of XRI
      associated variations in apolipoproteins apo B-100, apo C-III and apo E. RESULTS:
      XRI-associated apolipoprotein variants were not found. In contrast to the
      literature, an increased electrophoretic mobility was also observed for HDL (high
      density lipoproteins) from XRI patients. CONCLUSIONS: The underlying cause of the
      increased electrophoretic mobility of VLDL and HDL in XRI patients remains
      unclear. Future studies should investigate other apolipoproteins and verify the
      cholesterin sulfate concentrations reported for VLDL and HDL from XRI patients.

PMID- 10969405
TI  - [Therapy of lichen sclerosus et atrophicus vulvae with the CO2 silk touch laser].
AB  - A 50 year old woman with distinct lichen sclerosus et atrophicus was suffering
      from severe genital itching, dyspareunia and increasing urinary burning. Therapy
      attempts with topical glucosteroids and estrogens had been without effort.
      Treatment with CO2 laser in silk touch mode under insufflation anesthesia to an
      improvement of her skin lesions and a nearly complete remission of her symptoms.

PMID- 10969406
TI  - [Unilateral laterothoracic exanthema. Case report and review of the literature].
AB  - Unilateral laterothoracic exanthem (ULE) developed in a 4-year-old-boy on
      maintenance therapy for acute lymphatic leukemia (ALL). This is the second
      reported case of an association between ULE and leukemia. The etiology of ULE is
      unknown. Endemic cases, frequently associated signs of upper respiratory
      infections, and the occurrence of ULE in immunocompromised hosts are suggestive
      of an infectious process.

PMID- 10969407
TI  - [Sporotrichosis--fixed cutaneous and lymphocutaneous form].
AB  - Two patients were infected with sporotrichosis; one had the fixed cutaneous form,
      the other the lymphocutaneous form. Sporotrichosis schenckii was identified in
      both with a culture from a tissue biopsy. Both patients were successfully treated
      with itraconazole, one received 100 mg and the other 200 mg itraconazole daily
      over a 3 months period.

PMID- 10969408
TI  - [Subcutaneous panniculitic T-cell lymphoma].
AB  - Subcutaneous panniculitic T-cell lymphoma is categorized as a subtype of
      peripheral T-cell lymphoma. Patients typically present with nontender
      subcutaneous nodules. The characteristic histologic features include the presence
      of atypical lymphocytes and benign macrophages that infiltrate between the
      adipocytes of the subcutis mimicking panniculitis. We report a 75-year old
      patient with a three week history of asymptomatic subcutaneous nodules. The
      diagnosis of subcutaneous T-cell lymphoma was confirmed by immunohistological and
      molecular biological studies. Chemotherapy had to be interrupted due to a rapid
      worsening of the patient's general condition. She died few weeks after
      confirmation of diagnosis.

PMID- 10969409
TI  - [PUVA therapy as cosmetic indication?].

PMID- 10969410
TI  - [Increasing incidence of malignant melanoma].

PMID- 10969411
TI  - [Presentation of pyoderma gangraenosum in a dermatologic atlas of the early 19th
      century].
AB  - Pyoderma gangrenosum was first described in 1930 by Brunsting, Goeckermann and
      O'Leary. Nevertheless we found some illustrations in an atlas on dermatology,
      published by Marie-Nicolas Devergie in the first half of the 19th century, which
      appear to be pyoderma gangrenosum. In addition to discussions of typical
      syphilitic affections of the skin, Devergie's "Clinique de la Maladie
      Syphilitique" includes illustrations of gangrenous ulcers, which appeared
      unexpectedly after local and systemic therapy with mercury. Devergie interpreted
      those enlarging ulcers as a side effect of mercury therapy. Thus we were able to
      find evidence of pyoderma gangrenosum more than 100 years before first
      description in 1930. The etiology of this clinical picture is still unsettled.
      The favorite postulate has been a bacterial genesis which was the subject of
      numerous publications until the 1960s.

PMID- 10969412
TI  - [Comment on the contribution by P. Altmeyer, D. Seifarth, M. Bacharach-Buhles:
      "High dose intravenous immunoglobulin (IVIG) therapy in therapy refractory ANCA
      negative necrotizing vasculitis].

PMID- 10969413
TI  - [Comment on the contribution by M. Junger, A. Steins, B. Schlagenhauff and G.
      Rassner: "Microcirculation of cutaneous melanoma"].

PMID- 10969414
TI  - [Photodiagnostic tests. 3: Fluorescence diagnosis with delta-aminolevulinic acid
      induced porphyrins (FDAP) in dermatology].

PMID- 10969415
TI  - Narrative representations of moral-affiliative and conflictual themes and
      behavioral problems in maltreated preschoolers.
AB  - Examined whether maltreated preschoolers are more likely than nonmaltreated
      preschoolers to have fewer moral-affiliative and more conflictual narrative
      representations and whether these representations mediate child behavior
      problems. A structured narrative story-telling task was administered to assess
      representations, and independent ratings of behavior problems were obtained from
      teachers. The narratives of maltreated children contained more conflictual and
      fewer moral-affiliative themes. Maltreated children also exhibited more
      internalizing and externalizing behavior problems. A partial mediation effect of
      conflictual representations on the relation between child maltreatment and
      externalizing behavior problems was found. The results demonstrate the relation
      between child maltreatment and children's organization of their life experiences
      and their behavioral symptomatology.

PMID- 10969416
TI  - A preliminary study of the emotion understanding of youths referred for treatment
      of anxiety disorders.
AB  - Examined the emotion understanding of children and adolescents referred for
      treatment of Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM
      IV]; American Psychiatric Association, 1994) anxiety disorders (separation
      anxiety disorder, generalized anxiety disorder, or social phobia). Referred
      youths (n = 17) and nonreferred youths (n = 21) and their parents participated by
      completing self-report and parent-report questionnaires and structured diagnostic
      interviews. We interviewed all youths by using an emotion understanding
      interview. Referred youths demonstrated poorer understanding of hiding emotions
      and changing emotions compared with nonreferred youth. The 2 groups were not
      significantly different regarding their understanding of emotion cues and
      multiple emotions, however. No statistically significant relation emerged between
      general intelligence and emotion understanding. Future research directions are
      discussed.

PMID- 10969417
TI  - The role of parental emotional distress in parent report of child anxiety.
AB  - Evaluated the role of maternal and paternal emotional distress in parent report
      of anxiety in their child. Participants were 239 children (ages 7.5 to 15 years)
      diagnosed with a primary anxiety disorder and their parents (193 fathers, 238
      mothers). Parents individually completed the State-Trait Anxiety Inventory, the
      Beck Depression Inventory (BDI), and the State-Trait Anxiety Inventory for
      Children-Parent Version (a report of the child's anxiety). Children completed the
      State-Trait Anxiety Inventory for Children. Mothers and fathers reported more
      anxiety in their children than the children reported themselves. No significant
      relations were found between parental anxiety and parent report of child anxiety.
      When we examined girls only, both maternal and paternal BDI scores were
      significant predictors of parent report of the child's anxiety after we
      controlled for parental anxiety. Separate analyses by child age revealed that
      parent reports of child anxiety were more correlated with the self-reports of
      younger children. The implications of these findings are discussed.

PMID- 10969418
TI  - Coping and negative appraisal as mediators between control beliefs and
      psychological symptoms in children of divorce.
AB  - Examined control beliefs of children of divorce as predictors of their coping,
      negative appraisals for stressful events, and mental health problems. We tested
      whether coping and negative appraisal for stressful events mediated the relations
      between multiple dimensions of control beliefs and mental health problems.
      Different dimensions of control beliefs were related to different aspects of
      coping and negative stress appraisal. Internal control beliefs for positive
      events were related to both active and avoidant coping. Unknown control beliefs
      for positive events were related to higher active coping and higher negative
      appraisal. Unknown control beliefs for negative events were related to higher
      avoidant coping. In addition, evidence for mediation was found such that the
      effect of unknown control beliefs for positive events on mental health problems
      was mediated by negative appraisal. Implications and directions for further
      research are discussed.

PMID- 10969419
TI  - Threat perception bias in nonreferred, socially anxious children.
AB  - Investigated whether socially anxious children display a threat perception bias.
      A sample of 252 primary school children ages 8 to 13 years were exposed to
      ambiguous stories of social situations and instructed to find out as quickly as
      possible whether a story was scary. Furthermore, children were invited to tell
      how each story would end and to judge how they would feel when actually
      confronted with that situation. The main results can be summarized as follows.
      First, socially anxious children displayed lower thresholds for threat perception
      than control children. In other words, compared with control children, socially
      anxious children needed to hear fewer sentences of a story before deciding it was
      scary. Furthermore, socially anxious children more frequently perceived threat
      while listening to the stories than did control children. Finally, socially
      anxious children more often interpreted the stories as threatening and displayed
      higher levels of negative feelings and cognitions in relation to these stories
      compared with control children. These findings fit nicely in current information
      processing theories of childhood anxiety. An additional aim of this study was to
      investigate the convergent validity of the social phobia scales of 2 recently
      developed self-report questionnaires for measuring anxiety disorder symptoms in
      children: the Spence Children's Anxiety Scale (Spence, 1998) and the Screen for
      Child Anxiety Related Emotional Disorders (Birmaher et al., 1997). Results
      indicated that the social phobia scale of the Spence Children's Anxiety Scale and
      the extended social phobia scale of the Screen for Child Anxiety Related
      Emotional Disorders correlated substantially with a specific measure of social
      anxiety, the Social Anxiety Scale for Children-Revised.

PMID- 10969420
TI  - Social Anxiety Scale for Adolescents: normative data and further evidence of
      construct validity.
AB  - Replicates and extends prior work with the Social Anxiety Scale for Adolescents
      (SAS-A) by providing psychometric data, further evidence of construct validity,
      and large-sample based normative data. Participants were 2,937 students (1,431
      boys and 1,506 girls) in Grades 6, 7, 8, 9, and 11. Students completed the SAS-A,
      the Revised Children's Manifest Anxiety Scale (RCMAS), and the Children's
      Depression Inventory (CDI). Results replicated a three-factor structure for the
      SAS-A, with good internal consistencies for its subscales. Normative data were
      subdivided by sex and grade group. Construct validity included replication of
      prior relations with general anxiety (RCMAS) and depressive symptomatology (CDI).
      Implications of these results for further use and norming of the SAS-A are
      discussed.

PMID- 10969421
TI  - Tripartite model of depression and anxiety in youth psychiatric inpatients:
      relations with diagnostic status and future symptoms.
AB  - Examined the relation of the depression aspect of the tripartite model of
      depression and anxiety to the diagnostic status and future symptoms of two
      samples that included 74 child and adolescent psychiatric inpatients, ages 7 to
      17 years (M = 13.57, SD = 2.39), some with either internalizing or externalizing
      diagnoses. The tripartite model suggests that anhedonia (low positive affect, or
      PA) differentiates depression from other conditions, whereas generalized negative
      affect (NA) also characterizes depression but is not specific to it. In this
      study, differences among children in PA and NA were associated with depressive
      versus externalizing diagnostic status and with future symptoms of depression.
      Depressive disorder diagnoses were associated with the combination of low levels
      of PA and high levels of NA. Changes over time in depression, but not in anxiety,
      also were associated with the combination of low PA and high NA. Results provide
      support for the applicability, clinical utility, and extension of the tripartite
      model with children.

PMID- 10969422
TI  - Assessment of anxiety and depression in young children: support for two separate
      constructs.
AB  - Validated the interrelatedness of depression and anxiety in young children by
      testing four latent factor models: dual construct, unrelated; dual construct,
      correlated; single construct; and second-order or higher order analysis to test
      that depression and anxiety are primary constructs under the higher order factor
      of general affective distress. Children (N = 86) were ages 6 to 11, with mothers
      who were HIV-symptomatic or diagnosed with AIDS. Depression and anxiety measures
      included the Children's Depression Inventory (Kovacs, 1992), selected items from
      the Dominic-R (Valla, Bergeron, Berube, Gaudet, & St-Georges, 1994), and the
      Revised Children's Manifest Anxiety Scale (Reynolds & Richmond, 1985). Structural
      equation modeling was used to test the models. Model 2 (dual construct,
      correlated) fit the data better than did Models 1 and 3; results for the higher
      order model were identical to Model 2, suggesting the higher order model is
      equivalent to the dual-construct model.

PMID- 10969423
TI  - Peer functioning, family dysfunction, and psychological symptoms in a risk factor
      model for adolescent inpatients' suicidal ideation severity.
AB  - Examined models of suicidal ideation severity that include two psychosocial risk
      factors (i.e., peer and family functioning) and four domains of psychological
      symptoms (i.e., generalized anxiety, depression, conduct problems, and substance
      abuse/dependence). Participants were 96 psychiatric inpatients (32 boys, 64
      girls), ages 12 to 17, who were hospitalized because of concerns of suicidality.
      Adolescents completed a structured diagnostic interview, measures of suicidal
      ideation, and several dimensions of family and peer functioning. Results
      supported a model in which greater levels of perceived peer rejection and lower
      levels of close friendship support were associated directly with more severe
      suicidal ideation. In addition, indirect pathways included deviant peer
      affiliation and global family dysfunction related to suicidal ideation via
      substance use and depression symptoms. The results are among the first to
      demonstrate relations between suicidal ideation and several areas of adolescent
      peer functioning, as well as divergent processes for peer and family predictors
      of suicidal ideation.

PMID- 10969424
TI  - Screening for trauma in children and adolescents: the validity of the Traumatic
      Stress Disorder Scale of the screen for child anxiety related emotional
      disorders.
AB  - Examined the validity of the Traumatic Stress Disorder scale of the Screen for
      Child Anxiety Related Emotional Disorders (SCARED), a recently developed self
      report questionnaire measuring Diagnostic and Statistical Manual of Mental
      Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) defined
      anxiety disorders symptoms in children. A large sample of normal schoolchildren
      (N = 996) ages 7 to 19 years completed the SCARED. Children who scored high on
      the SCARED Traumatic Stress Disorder scale (i.e., trauma group; n = 43) and
      children who scored low on this scale (i.e., control group; n = 43) were then
      interviewed about their most aversive life event. In addition, children completed
      self-report questionnaires of traumatic experiences and posttraumatic stress
      disorder (PTSD) symptomatology. Results showed that children in the trauma group
      more frequently reported life events that independent judges considered to be
      'potentially traumatic' than did control children. Furthermore, children in the
      trauma group reported having experienced more traumatic incidents and had higher
      scores on PTSD-related questionnaires compared with control children. Moreover,
      trauma group children more frequently fulfilled DSM-IV criteria for PTSD than did
      control children. The results of this study support the validity of the Traumatic
      Stress Disorder scale of the SCARED.

PMID- 10969425
TI  - Social inhibition and overfriendliness as related to socioemotional functioning
      in 7- and 8-year-old children.
AB  - Examined high, medium, and low social inhibition groups in a Swedish sample (N =
      815) of 7- and 8-year-old children on the basis of parental reports about their
      children's reaction to novel social situations. High social inhibition was
      associated with increased levels of internalizing problems and low social
      competence. Among the low-inhibited children, we identified a subgroup by using
      an index of overfriendliness. Overfriendliness was associated with more
      internalizing, externalizing, and attention problems and lower prosocial
      orientation. The findings support the notion of high social inhibition as a risk
      factor for the development of internalizing problems and low social competence
      but question the view of low inhibition as descriptive of generally well
      functioning children. Rather, this is true for low-inhibited children only when
      they are also low in overfriendliness. Thus, the results point to a need for a
      better understanding of developmental pathways for both high- and low-inhibited
      children.

PMID- 10969427
TI  - Patterns and correlates of gun ownership among nonmetropolitan and rural middle
      school students.
AB  - Examined prevalence of gun ownership and the links among gun ownership, reasons
      for gun ownership, and antisocial behavior in a sample of nonmetropolitan and
      rural middle school students. Participants completed the Questionnaire for
      Students (Olweus, 1995) and included 6,263 students from 36 elementary and middle
      schools, of whom most were African American (range = 46%-95% per school). Reasons
      for gun ownership were strongly associated with rates of antisocial behavior.
      Youths who owned guns for sporting reasons reported rates of antisocial behavior
      that were only slightly higher than those reported by youths who did not own
      guns. Youths who owned guns to gain respect or to frighten others reported
      extremely high rates of antisocial behavior. These high-risk adolescent gun
      owners were likely to come from families of high-risk gun owners, associate with
      friends who were high-risk gun owners, and engage in high rates of bullying
      behavior. Findings suggest that effective violence prevention programs must
      target high-risk youths, address risk factors that go beyond individual settings,
      and address a comprehensive array of risk factors.

PMID- 10969426
TI  - Mother-infant interaction: effects of a home intervention and ongoing maternal
      drug use.
AB  - Examined the effects of a home-based intervention on mother-infant interaction
      among drug-using women and their infants. At 2 weeks postpartum, mothers and
      infants were randomly assigned to either an intervention (n = 84) or a control (n
      = 87) group. Control families received brief monthly tracking visits, and
      intervention families received weekly visits by trained lay visitors. Mother
      infant interaction was evaluated at 6 months through observation of feeding.
      Although there were no direct effects of the intervention, in the control group,
      mothers who continued to use drugs were less responsive to their babies than
      mothers who were drug free. In the intervention group, drug use was not
      associated with maternal responsiveness. Weekly home-based intervention may be a
      protective strategy for children of drug-using women because it disrupts the
      relation between ongoing maternal drug use and low maternal responsiveness.

PMID- 10969428
TI  - Peer-based differences among boys with ADHD.
AB  - Examined the peer interactions and peer acceptance of three groups of boys ages 8
      to 11 1/2 years: attention deficit hyperactivity disorder (ADHD), predominantly
      inattentive type; ADHD, combined type; and nonclinical controls (N = 45). Peer
      nominations were obtained from each boy's classroom. Newly acquainted peers
      consisting of boys from each of the 3 groups were observed for 3 play sessions,
      after which peer nominations were obtained. Both ADHD groups were more likely
      than nonclinical controls to receive lower social preference scores from peers in
      the classroom but not in the play groups. In both settings, boys from the
      predominantly inattentive group were more likely to be nominated as very shy,
      whereas boys from the combined type group were more likely to be nominated for
      starting fights and arguments. Observations of the play group showed that boys
      from the predominantly inattentive group displayed a marked pattern of social
      withdrawal. The findings suggest that the peer rejection experienced by these 2
      groups may result from very different social behavior patterns.

PMID- 10969429
TI  - The abilities of children with mental retardation to remember personal
      experiences: implications for testimony.
AB  - Investigated the abilities of children with mental retardation to remember the
      details of a personally experienced event. A simulated health check was
      administered to 20 children with mental retardation and 40 normally developing
      children, half matched on mental age (MA) and half matched on chronological age
      (CA) with the children with mental retardation. The children's memory was
      assessed immediately after the health check and 6 weeks later. Overall, the
      children with mental retardation accurately recalled the health check features,
      provided detail, and resisted misleading questions about features that did not
      occur. The group with mental retardation performed similarly to the MA matches on
      virtually all of the memory variables. The children with mental retardation
      performed worse than the CA matches on most of the memory variables, although
      they were able to recall a similar number of features. The findings are discussed
      in terms of the ability of children with mental retardation to provide accurate
      testimony.

PMID- 10969430
TI  - Risk factors for dental fluorosis: a review of the recent literature.
AB  - The decline in dental caries prevalence and incidence in developed countries over
      the last two decades is considered to be largely due to the widespread use of
      fluoride. Simultaneously, with the decline in caries, an increase in the
      prevalence of dental fluorosis has been noticed. The increase is in the mild and
      very mild forms of fluorosis, and is proportionally greater in non-fluoridated
      areas than in fluoridated areas. This is because of the increase in the mean
      fluoride intake from all sources since the 1940s. The increase in fluorosis
      prevalence prompted numerous studies on risk factors for fluorosis. As a result
      the literature over the last two decades has also reported numerous studies with
      differing and confusing results. This paper describes for the clinician the
      condition and summarizes the recent literature on the risk factors for fluorosis.
      Only well conducted studies evaluating risk factors or indicators and quantifying
      the risk for dental fluorosis from the 1980s through the 1990s time period were
      included in this review. Four major risk factors were consistently identified:
      use of fluoridated drinking water, fluoride supplements, fluoride toothpaste, and
      infant formulas before the age of six years.

PMID- 10969431
TI  - Success rates of formocresol pulpotomy and indirect pulp therapy in the treatment
      of deep dentinal caries in primary teeth.
AB  - PURPOSE: This study was performed to retrospectively evaluate treatment of deep
      caries in primary molars with formocresol pulpotomy (FP) and indirect pulp
      therapy (IPT). METHODS: 133 primary molars with deep caries approaching the pulp
      were treated with FP (N = 78) or IPT (N = 55) and followed 2-7 years. All IPTs
      received immediate stainless steel crowns (SSCs); 61 FPs got an immediate SSC, 13
      an intermediate restorative material (IRM), and 4 amalgam. Thirteen IPTs and 25
      FPs had pre-operative pain compatible with a diagnosis of reversible pulpitis.
      Treatment notes and radiographs were independently assessed. RESULTS: Overall IPT
      success was 93% (51/55) versus 74% (58/78) for FP. Molars with pain compatible
      with a diagnosis of reversible pulpitis were successfully treated by IPT 85%
      (11/13) versus 76% (19/25) for FP. FP-treated molars exhibited earlier
      exfoliation 38% (30/78), while all IPT molars exhibited normal exfoliation. FPs
      receiving immediate SSCs had 50/61 (82%) succeed; FPs restored with an IRM
      temporary succeeded 5/13 (39%), amalgam 3/4 (75%). CONCLUSIONS: IPT success was
      significantly higher than FP (P = 0.01) in the treatment of deep caries. Both IPT
      and FP were successful in treating teeth with pain compatible with the diagnosis
      of reversible pulpitis. FP significantly hastened the exfoliation of pulpotomized
      primary molars (P = 0.001). IPT in primary teeth can be successfully used in a
      one step procedure. SSCs placed immediately after FP significantly increased FP
      success vs. FP followed by IRM temporary (P = 0.01).

PMID- 10969432
TI  - Prevalence of oral soft tissue lesions in HIV-infected minority children treated
      with highly active antiretroviral therapies.
AB  - PURPOSE: This project studied the prevalence of oral soft tissue disease in HIV
      infected children treated with highly active antiretroviral therapy (HAART).
      METHODS: Thirty-eight HIV-infected children participated in the study. Twenty
      three of these patients were treated with HAART while 14 received exclusively
      reverse transcriptase inhibitors (RTI) and served as controls. The children were
      examined three times at approximately one-month intervals while their health
      history and laboratory data were abstracted from medical charts. Analyses were
      performed to determine differences in lesion prevalence between treatment groups
      as well as between lesion and no lesion groups with regard to immune differences.
      RESULTS: Thirty patients (79%) had oral lesions detected in at least one visit.
      There were no differences in specific lesion prevalence between HAART compared
      with RTI-treated children. However, a trend for more oral candidiasis in the
      latter group was observed. Subjects with oral soft tissue lesions had lower CD4
      counts (P = 0.04) and percentage (P = 0.01) but similar viral loads when compared
      to patients without oral soft tissue disease. CONCLUSIONS: HAART does not appear
      to significantly affect oral soft tissue disease prevalence in HIV-infected
      children. Presence of lesions was associated with decreased immunity and may
      signal advancing disease.

PMID- 10969433
TI  - Mucoepidermoid carcinoma of the palate in a child.
AB  - Salivary gland tumors are rare in children but when they involve the minor
      salivary glands, there is an increased risk that they will be malignant. The
      clinical and histopathologic features of a palatal mucoepidermoid carcinoma in an
      8 year-old boy are presented. Differentiating this entity from common reactive
      and benign neoplastic lesions is discussed in order to prevent a delay in
      diagnosis and the potential for mismanagement.

PMID- 10969434
TI  - The atraumatic restorative treatment (ART) approach for primary teeth: review of
      literature.
AB  - There is widespread interest in and increasing usage of the atraumatic
      restorative treatment (ART) technique or approach for the restoration of primary
      teeth, especially in developing countries. However, most of the published reports
      of the clinical performance of newer, more-viscous esthetic conventional glass
      ionomer restorative cements marketed for the technique have been from short-term
      studies, and there have been very few reports comparing different types of
      restorative materials and methods of cavity preparation. After 12 months, Class
      II/multisurface and Class III/IV ART restorations have generally shown success
      rates of approximately 55-75% and 35-55%, respectively. Failures were usually
      from restoration losses and fractures. Class I & V/single-surface ART
      restorations have had much better short-term success rates of approximately 80
      90%. Recurrent caries was not a concern at this time, but occlusal wear was
      relatively high. Further improvements in the mechanical and adhesive properties
      of the newer cements are still required, together with further clinical
      investigations of the remineralization of shallow open preparations as an
      alternative to placing restorations. The ART approach is readily accepted by
      children and has resulted in the retention of many teeth that would otherwise
      have been extracted.

PMID- 10969435
TI  - Information on the Web.

PMID- 10969436
TI  - Mutans streptococci prevalence in Puerto Rican babies with cariogenic feeding
      behaviors.
AB  - PURPOSE: Previous studies have demonstrated that babies are at higher risk for
      mutans streptococci (ms) colonization if their mothers have dense salivary ms
      reservoirs relative to babies who have mothers with negligible salivary
      reservoirs. This communication provides data that identifies another potential
      risk factor (use of a nursing bottle at bedtime and/or naptime that contains a
      substrate other than water) for baby infection by ms. METHODS: The study
      population consisted of 60 babies (28 males/32 females; mean age 15 mos; age
      range 12-18 mos) who were all healthy, caries free, and slept with a nursing
      bottle that contained a substrate other than water (NB+). Pooled maxillary
      incisor plaque and saliva samples were obtained and immediately placed in Reduced
      Transparent Fluid (RTF); they were serially diluted and plated onto Mitis
      Salivarius Agar plus Bacitracin (MSB) and blood agar plates within 4 hours of
      collection; the plates were incubated in an anaerobic environment for 48 h at 37
      C and then placed for 24 h under aerobiosis prior to examination; representative
      ms colonies were isolated and subjected to mannitol and sorbitol fermentation
      tests for taxonomic verification. Plates with colony counts between 20 and 300
      were utilized to determine the % of ms in each sample. RESULTS: Fifty one of the
      60(85%) babies harbored ms in at least 1 of the 2 samples. The 95% confidence
      interval for the proportion of subjects with detectable levels of ms was 73%-93%.
      Fisher's exact test showed that babies 16-18 mos age were more likely to have
      detectable levels of ms than babies 12-15 mos age (p = 0.01). Levels of ms in
      plaque and saliva were as follows: < 0.1% (plaque 27/51, mean age 15 mos, sd
      1.77; saliva 28/51, mean age 15 mos, sd 1.76); 0.1%-1.0% (plaque 4/51, mean age
      14 mos, sd 1.5; saliva 6/51, mean age 15 mos, sd 1.46); > 1.0% (plaque 14/51,
      mean age 16 mos, sd 2.1; saliva 11/51, mean age 16 mos, sd 1.91). The density of
      infection did not vary by age for plaque (P = 0.32) or saliva (P = 0.64).
      CONCLUSION: These findings support the concept that NB+ is a strong indicator for
      ms infection in Puerto Rican babies; that prevalence of infection increases with
      age; and that density of infection does not vary with age in this population.

PMID- 10969437
TI  - Future caries susceptibility in children with early childhood caries following
      treatment under general anesthesia.
AB  - PURPOSE: The purpose of this study was to assess the susceptibility of children
      to the future development of caries following comprehensive treatment for early
      childhood caries (ECC) under general anesthesia. METHODS: The patients selected
      for this retrospective study were identified by analyzing dental records of
      children receiving treatment at the Franciscan Children's Hospital &
      Rehabilitation Center, Boston, MA (FCH & RC). In total, 4,143 records were
      reviewed. Of these, ECC was diagnosed in 42 patients before their admission to
      the operating room. Thirty-one control children were selected randomly from the
      dental records reviewed at FCH & RC. The control group was initially caries-free.
      The caries status of the children diagnosed with ECC was evaluated and compared
      with the control group. Children in both groups were seen for recall at intervals
      of six to nine months over a two-year period. The carious lesions were recorded
      in two categories; new smooth surface caries (NSSC) and new pit and fissure
      caries (NPFC). RESULTS: Thirty-three of 42 (79%) ECC children compared to nine of
      31 (29%) control children had detectable carious lesions at subsequent recall
      visits. Children with ECC demonstrated a mean number of 3.2 +/- 3.3 new carious
      lesions compared to a mean of only 0.8 +/- 1.6 carious lesions in the control
      group. These differences were statistically significant (t71 = 3.8; P < 0.001).
      In addition, of the 42 patients treated for ECC under general anesthesia, seven
      (17%) required retreatment under general anesthesia within two years following
      their initial full-mouth rehabilitation. The prevalence of NSSC in the ECC group
      was significantly higher than the control group (t71 = 3.5; P < 0.001).
      CONCLUSIONS: Despite increased preventive measures implemented for children who
      experienced ECC, this study concluded that this group of children is still highly
      predisposed to greater caries incidence in later years. These findings strongly
      suggest that more aggressive preventive therapies may be required to prevent the
      future development of carious lesions in children who experienced ECC.

PMID- 10969438
TI  - A comparison between articaine HCl and lidocaine HCl in pediatric dental
      patients.
AB  - PURPOSE: Three identical single-dose, randomized, double-blind, parallel-group,
      active-controlled multicenter studies were conducted to compare the safety and
      efficacy of articaine HCl (4% with epinephrine 1:100,000) to that of lidocaine
      HCl (2% with epinephrine 1:100,000) in patients aged 4 years to 79 years, with
      subgroup analysis on subjects 4 to < 13 years. METHODS: Fifty subjects under the
      age of 13 years were treated in the articaine group and 20 subjects under the age
      of 13 were treated with lidocaine. Subjects were randomized in a 2:1 ratio to
      receive articaine or lidocaine. Efficacy was determined on a gross scale
      immediately following the procedure by having both the subject and investigator
      rate the pain experienced by the subject during the procedure using a visual
      analog scale (VAS). Safety was evaluated by measuring vital signs before and
      after administration of anesthetic (1 and 5 minutes post-medication and at the
      end of the procedure) and by assessing adverse events throughout the study.
      Adverse events were elicited during telephone follow-up at 24 hours and 7 days
      after the procedure. RESULTS: Pediatric patients received equal volumes, but
      higher mg/kg doses, of articaine than lidocaine during both simple and complex
      dental procedures. Pain ratings: Articaine: VAS (Visual Analogue Scale) scores
      (from 0 to 10 cm) by patients 4 to < 13 years of age were 0.5 for simple
      procedures and 1.1 for complex procedures, and average investigator scores were
      0.4 and 0.6 for simple and complex procedures, respectively. Lidocaine: patients
      0.7 (simple) and 2.3 (complex); investigators 0.3 (simple) and 2.8 (complex).
      Adverse events: No serious adverse events related to the articaine occurred. The
      only adverse event considered related to articaine was accidental lip injury in
      one patient. CONCLUSIONS: VAS scores indicate that articaine is an effective
      local anesthetic in children and that articaine is as effective as lidocaine when
      measured on this gross scale. Articaine 4% with epinephrine 1:100,000 is a safe
      and effective local anesthetic for use in pediatric dentistry. Time to onset and
      duration of anesthesia are appropriate for clinical use and are comparable to
      those observed for other commercially available local anesthetics.

PMID- 10969439
TI  - An investigation of the transverse technique of dentifrice application to reduce
      the amount of fluoride dentifrice for young children.
AB  - PURPOSE: Recent studies have shown an increase in the prevalence of fluorosis.
      Consequently, recommendations for the use of a small quantity of fluoride
      dentifrice, 0.25 to 0.5 g or the equivalent of a "pea size" amount for children,
      have been made. This study evaluated a method of placing dentifrice in a
      transverse relation to the bristles (TT) and compares it to the standard
      technique used (ST) and to the "pea size" recommendation (PS). METHODS: The study
      was conducted in three phases: the first was in a laboratory setting using 22
      commercial brands of children's toothbrushes; the second evaluated various
      recommendations with 240 mothers (Brazilian and Peruvian); and the third
      evaluated these recommendations in 135 Peruvian children (ages 4 to 6). RESULTS:
      The results showed that the mean quantity of dentifrice used with ST, PS, and TT
      was 0.58 g, 0.34 g, and 0.27 g for the mothers and 0.46 g, 0.29 g, and 0.24 g for
      the children, respectively. The average TT obtained through multiple weighing of
      22 children's toothbrushes was 0.22 g. Both recommendations (PS and TT) reduced
      the amount of dentifrice used. However, TT also yielded a smaller variation
      range. Mothers and children learn easily and prefer TT. CONCLUSION: This
      technique could be recommended for young children in order to decrease the amount
      of fluoride dentifrice used, hence minimizing the potential inadvertent ingestion
      of fluoride dentifrice.

PMID- 10969440
TI  - Microcanals of dentin associated with maxillary primary anterior teeth.
AB  - PURPOSE: This study was performed to estimate the prevalence of giant dentin
      tubules or microcanals in primary maxillary anterior teeth. METHODS: One hundred
      sixty eight extracted or exfoliated primary maxillary anterior teeth were
      sectioned and examined by optical microscopy and image analysis. Differences in
      the proportion of teeth with microcanals among tooth types were tested by using
      the Pearson chi-square test. RESULTS: Microcanals, having the appearance of
      enlarged dentin tubules, were found in approximately 20% of primary central and
      lateral incisors, but were significantly less prevalent (3%) in primary cuspids.
      Microcanals occurred in a mesial distal axial plane and ran between the DEJ and
      the pulp chamber. When present they numbered between 1 and 43, with mean numbers
      of 20 and 16 in central and lateral incisors, respectively. The microcanals
      ranged in size between 5 and 70 microns, compared to normal dentin tubule
      diameters of approximately 1 micron. CONCLUSIONS: Microcanals are relatively
      common in primary maxillary incisors, but uncommon in primary cuspids. Additional
      work is needed to establish their prevalence in various teeth of both primary and
      permanent dentition.

PMID- 10969441
TI  - Comparison of palatal and alveolar cysts of the newborn in premature and full
      term infants.
AB  - PURPOSE: The frequency of cysts has been reported to be high in newborns, but
      they are rarely seen after three months of age. There has been a lack of studies
      describing the clinical prevalence in the premature infant after 22 weeks and
      less than 37 weeks gestation. The purpose of this study was to quantify and
      describe the clinical prevalence of palatal and alveolar cysts in premature
      infants as compared to full term infants. METHODS: Sixty premature infants, born
      at less than 37 weeks gestation, and 60 term infants, born greater than 37 weeks
      gestation, were examined in the first few days after birth for the presence of
      palatal and alveolar cysts. Alveolar cysts were further classified according to
      location as either maxillary or mandibular, and anterior or posterior.
      Information regarding birth weight, race, sex, and maternal health during
      pregnancy was also collected. RESULTS: The prevalence of palatal cysts in the
      premature infant (9%) is less than the prevalence in term infants (30%), to a
      statistically significant level (P < 0.004, by the Fisher's exact test).
      Differences between preterm and term infants were also noted in the prevalence of
      maxillary anterior alveolar cysts, (preterm having 27% and term 58%, P < 0.0005)
      and maxillary posterior alveolar cysts (preterm 2% and term 10%, P < 0.06). The
      prevalence of palatal and maxillary alveolar cysts was demonstrated to increase
      with increasing gestational age, increasing postnatal age, and increasing birth
      weight (by plots of cumulative percent). No significant differences were found
      for gender or for race. CONCLUSION: The prevalence of palatal and alveolar cysts
      in the premature infant is less than the prevalence in the full term infant to a
      statistically significant level. Palatal and maxillary alveolar cysts increase
      with increasing gestational age, post-natal age, and birth weight.

PMID- 10969442
TI  - Appointment-keeping behavior of Medicaid-enrolled pediatric dental patients in
      eastern Iowa.
AB  - PURPOSE: The purpose of this prospective study was to assess the appointment
      keeping behavior of Medicaid-enrolled pediatric dental patients in three Eastern
      Iowa practices. METHODS: During the month of October 1998, a tally was kept of
      all patient appointments at a private pediatric dental office, a public health
      dental clinic, and a university-based pediatric dentistry clinic. Patients were
      categorized as either Medicaid or non-Medicaid. Appointment behavior categories
      were defined as: On time; Failure; Late-notice Cancellation (less than 24 hours
      notice); and Tardy (greater than 10 minutes). The data was entered in SPSS and
      analyzed using the chi square statistic. Statistical significance was P < 0.05.
      RESULTS: A total of 1,406 appointments were recorded for all three sites.
      Overall, patients on Iowa Medicaid had higher appointment failure, late-notice
      cancellation, and tardiness rates than non-Medicaid patients at all three
      clinics. However, these differences were only statistically significant for the
      private office and the university-based clinic. Failed appointment rates for
      Medicaid patients were much higher at the private office (38%) than at the other
      two sites. CONCLUSION: Consistent with anecdotal reports from dentists, Medicaid
      patients had higher rates of broken appointments than did non-Medicaid patients,
      particularly in a private practice setting.

PMID- 10969443
TI  - Pediatric dentistry workforce issues: a task force white paper. American Academy
      of Pediatric Dentistry Task Force on Work Force Issues.
AB  - The number of current practitioners, academicians, and researchers in Pediatric
      Dentistry is clearly not adequate to meet the need and demand. The shortage in
      academia is dire. Simply put, not enough pediatric dentists are being trained.
      The rate limiting factor is the number of training positions. The American
      Academy of Pediatric Dentistry established a "Task Force on Work Force Issues"
      approximately 18 months ago and charged that group to seek methods for creating
      more training positions. This paper reflects the Task Force deliberations,
      documents the shortage of pediatric dental specialists, and recommends tactics
      for amelioration.

PMID- 10969444
TI  - Surgical treatment for peroneal nerve palsy.
AB  - BACKGROUND: Peroneal nerve palsy is the most frequently encountered
      mononeuropathy of the lower extremities. Although many studies advocated
      spontaneous resolution of peroneal nerve palsy, more recent studies confirmed
      obvious improvement with surgical treatment techniques. METHODS: This study
      reviewed the results obtained from surgically treated peroneal nerve palsy in 14
      patients who were admitted to our hospital between 1990 and 1996. The patients
      consisted of 12 males and two females with an average age of 31 years (range, 12
      68 years). Peroneal nerve palsy in these patients was caused by direct or
      indirect injury, as confirmed by clinical examination and electromyography. The
      status of the nerve was observed for at least 4 months and explored when the
      nerve failed to reveal evidence of recovery. The nerve was decompressed, repaired
      or reconstructed by nerve grafting, according to the status of the injury. Weber
      scales were used to assess the peripheral neuropathies preoperatively and
      postoperatively. RESULTS: At a mean of 23 months (range, 11-61 months), nerve
      palsy scores improved from an average of 5 points to 3.14 points. Despite the
      small number of patients, our results indicated that the time interval between
      onset of injury and date of surgical treatment (p < 0.05) was the most
      significant factor to influence the prognosis of surgery. Results obtained from
      surgery were not related to the method of treatment, length of nerve graft or
      mechanism of injury. CONCLUSIONS: Because peroneal nerve palsy does not always
      resolve spontaneously, this study favored early surgical exploration for peroneal
      nerve dysfunction, based on at least 4 months of follow-up.

PMID- 10969445
TI  - Problem-based, small-group tutorial learning in clinical neurology for second
      year medical students.
AB  - BACKGROUND: Problem-based learning (PBL) in small-group tutorials has been a
      trend in medical education. Chinese students are known to be reserved and
      passive; thus, they may not be adaptable to PBL. Neuroanatomy, important to
      clinical neurology, is difficult to learn. We incorporated clinical neurology
      with PBL, complementary to the traditional neuroanatomy curriculum, to evaluate
      the feasibility of PBL for Chinese students in Taiwan. METHODS: Forty-two second
      year medical students and seven tutors participated in the clinical neurology PBL
      small-group tutorials. Twelve case reports were discussed weekly beginning in
      February, 1999. Each case was designed to meet the progressive curriculum of the
      neuroanatomy course. The tutors evaluated the students by the degree of their
      preparation, participation, key-point comprehension and interaction. All tutors
      and students filled out questionnaires at the end of each session. RESULTS: The
      majority of the students and tutors agreed that the case materials were clearly
      written. Ninety percent of the students agreed that the case materials matched
      the traditional content of neuroanatomy. Eighty-five percent of students and 71%
      of tutors were satisfied and found the class rewarding. Ninety-one percent of
      students and 74% of tutors were in favor of PBL being continued. CONCLUSIONS:
      This preliminary PBL, small-group tutorial learning in clinical neurology showed
      satisfactory results and was, indeed, complementary to a traditional neuroanatomy
      course. The students, as early as during the second year of their medical school
      education, were able to learn through the PBL. More integration of basic and
      clinical sciences by PBL may be considered in future curricula designs.

PMID- 10969446
TI  - Combination chemotherapy with tamoxifen, ifosfamide, epirubicin and cisplatin in
      extensive-disease small-cell lung cancer.
AB  - BACKGROUND: A study of tamoxifen, ifosfamide, epirubicin and cisplatin (TIEP)
      chemotherapy was conducted in patients with extensive-disease, small-cell lung
      cancer (SCLC) to assess response and toxicity. METHODS: From November, 1997, to
      February, 1999, 11 patients were treated, including six chemo-naive patients and
      five patients previously treated with cisplatin plus etoposide (EP). The
      treatment regimen included tamoxifen 60 mg twice daily orally on days 1 to 3,
      ifosfamide 3 g/m2 intravenous (i.v.) infusion for 60 minutes with mesna on day 2,
      epirubicin 50 mg/m2 i.v. bolus on day 2 and cisplatin 60 mg/m2 i.v. for 60
      minutes on day 2, every 4 weeks for up to six cycles. RESULTS: All patients were
      evaluated for toxicity and response rate. As expected, the major toxicity was
      myelosuppression. Grade 3 or 4 leukopenia or neutropenia occurred in all patients
      during treatment. Two patients (18.2%) experienced fever in association with the
      neutropenia, one of whom died of sepsis. Grade 3 anemia occurred in two patients
      (18.2%) during treatment. Toxicities other than neutropenia and anemia were
      limited. After two cycles of treatment, five of six chemo-naive patients (83%),
      and one of five previously treated patients (20%) attained a partial response
      (overall 54.5%, 95% confidence interval 25%-83.9%). Median survival time was 8.5
      and 6 months in chemo-naive and previously EP-treated patients, respectively. The
      response rate and median survival time in chemo-naive patients did not improve
      compared with a previous study of ifosfamide plus etoposide undertaken 4 years
      earlier. CONCLUSIONS: Although TIEP is an active combination regimen with an
      acceptable toxicity profile in Chinese patients with extensive-disease SCLC, it
      showed no remarkable benefit compared with other regimens used in chemo-naive
      patients. The 20% response rate and median survival of 6 months in EP-treated
      patients deserve further study.

PMID- 10969447
TI  - Cardiac manifestations of fatal enterovirus infection during the 1998 outbreak in
      Taiwan.
AB  - BACKGROUND: An outbreak of hand-foot-and-mouth disease caused by enterovirus
      infection occurred in Taiwan in 1998 and more than 70 infants and children with
      fulminant courses died. We compared the cardiac manifestations of fatal cases
      with patients who survived the enterovirus infection. METHODS: A total 187
      patients with enterovirus infection were treated at Taichung Veterans General
      Hospital between April and June 1998. Enterovirus infection was diagnosed by
      history, clinical features, polymerase chain reaction study and/or viral culture.
      Cardiac examinations including complete physical examinations,
      electrocardiography and echocardiography were performed on seven cases (group I)
      with or without central nervous system (CNS) involvement, 30 patients with CNS
      involvement (group II), and 150 patients without CNS involvement (group III).
      RESULTS: There were no significant differences in sex distribution, days of
      fever, heart rate, systemic blood pressure or time from the onset of symptoms to
      hospital admission among the three groups. All group I patients had features of
      acute congestive heart failure, pulmonary edema and neurologic signs except one
      who presented with right-sided heart failure and neurologic signs. The
      echocardiographic findings of group I were a lower fractional shortening, lower
      ejection fraction, and more severe and higher incidence of mitral regurgitation
      (p < 0.01) than in groups II and III, but there were no significant differences
      in end-systolic wall stress, left ventricular end-diastolic internal dimension
      and incidence of pericardial effusion among the three groups. CONCLUSIONS: We
      conclude that seven infants and children (group I) died due to either severe
      cardiomyopathy or encephalopathy. The possible pathogenesis of enterovirus
      infection leading to death is reviewed and analyzed.

PMID- 10969448
TI  - Relative bioavailability of salmon calcitonin given intramuscularly.
AB  - BACKGROUND: Salmon calcitonin, a polypeptide hormone, is used in the treatment of
      osteoporosis, hypercalcemia and Paget's disease. The purpose of this study was to
      evaluate the pharmacokinetics and relative bioavailability of two salmon
      calcitonin products, Miacalcic (Novartis Pharmaceuticals, Basle, Switzerland) and
      Calcinin (Purzer Pharmaceuticals, Taipei, Taiwan). METHODS: This was a
      randomized, single-dose, crossover study conducted under fasting conditions with
      a washout period of 1 week between doses. Ten healthy male subjects were enrolled
      in this study. Each subject received a 100 IU dose (20 micrograms; 50 IU/ampule x
      2) of salmon calcitonin intramuscularly (i.m.) followed by collection of blood
      samples at specified time intervals. Serum salmon calcitonin concentrations were
      measured using a validated radioimmunoassay method with a detection limit of 15.0
      pg/ml. Values for the area under the serum concentration from time zero to last
      time and infinity curve (AUC0-t and AUC0-infinity), peak concentration (Cmax),
      time to peak concentration, terminal first order rate constant, terminal half
      life, mean residence time, total clearance divided by absolute bioavailability,
      onset time, maximal effect and duration were compared for each product. RESULTS:
      The 90% confidence intervals for AUC0-t, AUC0-infinity and Cmax after logarithmic
      transformation were 93.2% to 113.1%, 97.2% to 114.9% and 84.9% to 108.0%,
      respectively. CONCLUSIONS: Based on the two one-sided tests procedure, we
      conclude that Miacalcic and Calcinin are bioequivalent.

PMID- 10969449
TI  - Five-year follow-up of patients with recurrent postmenopausal bleeding.
AB  - BACKGROUND: The most common symptom of endometrial cancer is postmenopausal
      bleeding. For women who present with postmenopausal bleeding and a benign tissue
      diagnosis, recurrent bleeding is a worrisome problem. We evaluated such patients
      to search for a model of good management. METHODS: We studied women aged 50 years
      or over who presented with postmenopausal bleeding and underwent either
      dilatation and curettage (D & C) or endometrial biopsy from 1990 to 1991 at Long
      Island Jewish Medical Center, New Hyde Park, NY, USA. The selected patients were
      monitored for 5 years, until 1996. For those who had an initial benign tissue
      diagnosis and presented with recurrent postmenopausal bleeding in the following 5
      years, we studied the differences in histologic diagnoses. RESULTS: Seventy-seven
      patients had an initial benign tissue diagnosis of postmenopausal bleeding
      followed by recurrent bleeding. After repeat D & C or endometrial biopsy (2-6
      times), 16 patients (20.8%) had endometrial cancer or endometrial complex
      hyperplasia. Of the 12 patients who had two or more benign tissue diagnoses,
      seven (58.3%) had tumors found in subsequent surgery. The diagnoses included
      endometrial cancer, ovarian cancer, cervical cancer and benign tumor.
      Postmenopausal women aged 65 years or over had a much greater chance (13/29,
      44.8%) of having endometrial cancer or complex hyperplasia than women aged below
      65 years (6/48, 12.5%) who presented with recurrent postmenopausal bleeding and
      had an initial benign tissue diagnosis (c2 = 7.893, p = 0.0050). CONCLUSIONS:
      Although the initial tissue diagnosis might be benign, the possibility of
      endometrial cancer or complex hyperplasia cannot be ruled out for women with
      recurrent postmenopausal bleeding. Diagnostic D & C or endometrial biopsy
      combined with other tools (vaginal ultrasound, hysteroscopy, transvaginal
      sonohysterography) are more reliable for evaluating women with recurrent
      postmenopausal bleeding than D & C or endometrial biopsy only. If these
      diagnostic results are negative, a total hysterectomy with bilateral salpingo
      oophorectomy should be considered to reduce the risk of endometrial cancer in
      women who present with recurrent bleeding.

PMID- 10969450
TI  - Cervical carcinoma: assessment of parametrial invasion and lymph node metastasis
      with magnetic resonance imaging.
AB  - BACKGROUND: Clinical tumor staging of cervical carcinoma has its limitations. The
      purpose of this study was to stage cervical carcinoma by magnetic resonance
      imaging (MRI), with an emphasis on the assessment of parametrial invasion and
      pelvic lymph node metastasis. METHODS: MRI was performed in 51 women with tissue
      proven cervical carcinoma 2 weeks prior to surgery. Images were analyzed for
      parametrial invasion, pelvic lymph node metastasis and tumor stage. The results
      were compared with the histopathologic findings after surgery in all patients.
      RESULTS: In assessing parametrial invasion, MRI had an accuracy of 94%. In
      assessing pelvic lymph node metastases, MRI was accurate in 86.3% of cases. In
      determining stage of disease, MRI had an accuracy of 76.5%. The accuracy of MRI
      in differentiating localized (< or = stage IIA) from advanced disease (> or =
      stage IIB) was 94.1%. CONCLUSIONS: MRI is accurate in the evaluation of
      parametrial invasion and lymph node metastases and in the differentiation of
      localized and advanced disease. MRI is beneficial in planning treatment for
      patients with cervical cancer.

PMID- 10969451
TI  - Population-based study on prevalence and risk factors of age-related cataracts in
      Peitou, Taiwan.
AB  - BACKGROUND: Age-related cataracts are the main cause of blindness throughout the
      world. Nonetheless, population-based data on the epidemiology of age-related
      cataracts among Taiwanese populations are not readily available. This study was
      conducted to estimate the prevalence of age-related cataracts and to determine
      the relationships of age, gender, blood pressure, diabetes and smoking to the
      risks of age-related cataracts in an urban Taiwanese population. METHODS: The
      study was part of a population-based survey of eye diseases among residents aged
      50 years or older in Peitou Precinct, Taipei, Taiwan. Of the 2,700 eligible
      persons, 2,038 (75.5%) underwent a standard evaluation protocol including dilated
      slit-lamp examination, a questionnaire of medical and ophthalmic histories and
      blood pressure measurement. RESULTS: Among the participants, 1,040 were diagnosed
      with age-related cataracts. The prevalence was 51.0% (95% confidence interval,
      48.9%-53.2%). Nuclear opacity was the most prevalent type (718/1,040; 35.2%) of
      cataracts, followed by posterior subcapsular opacity (311/1,040; 15.3%) and
      cortical opacity (163/1,040; 7.8%). An increased risk of age-related cataracts
      was associated with female gender (p = 0.002). When a single type of lens opacity
      was considered, diabetes was significantly associated with a posterior
      subcapsular cataract (p = 0.022). Overall, older women with diabetes and
      relatively lower diastolic blood pressure were more likely to have age-related
      cataracts. CONCLUSIONS: The study provided the first prevalence data on age
      related cataracts in an urban Taiwanese population and highlighted the
      relationships of age, gender, blood pressure and diabetes to the frequency and
      type of age-related cataracts. The results can assist in the design and
      implementation of intervention programs to reduce the prevalence of age-related
      cataracts.

PMID- 10969452
TI  - Gastroesophageal variceal bleeding caused by hepatoportal arteriovenous fistula.
AB  - Hepatoportal arteriovenous fistulas are usually traumatic in origin and may
      result in portal hypertension and serious complications. We report a 34-year-old
      female with a history of abdominal trauma, who developed symptoms of tarry stools
      and hematemesis 5 years later. Esophageal and gastric varices with bleeding were
      diagnosed by upper gastrointestinal endoscopy. Abdominal ultrasonography and
      computerized tomography favored noncirrhotic portal hypertension. An extrahepatic
      hepatoportal arteriovenous fistula was demonstrated by angiography. The patient
      underwent surgery to correct the condition. The liver had a smooth surface and
      both the common hepatic and gastroduodenal arteries were ligated during surgery.
      The postoperative course was uneventful. The varices later disappeared.

PMID- 10969453
TI  - Aberrant cervical carotid artery.
AB  - Aberrant cervical carotid artery is an uncommon anomaly. Because this anomaly can
      lie in close proximity to the midline of the posterior part of the pharynx, it
      poses a significant risk during both major pharyngeal tumor resection and less
      extensive procedures such as tonsillectomy, adenoidectomy and
      palatopharyngoplasty. Five cases of aberrant cervical carotid artery were
      encountered and diagnosed using computerized tomography. In all five cases, the
      anomalous finding did not correlate with the presenting symptoms. Computerized
      tomographic images of these cases are provided. A review of the literature and
      the embryology of the aberrant carotid artery are presented. Awareness of the
      anomaly by radiologists and surgeons is essential to avoid accidental injury to
      the vessel during surgery.

PMID- 10969454
TI  - Parkinsonism as an initial manifestation of brain tumor.
AB  - Parkinsonism secondary to neoplasm is uncommon. We report two patients with
      bilaterally symmetric parkinsonism as the initial presentation of their brain
      tumors. The first patient was a 71-year-old woman who presented with a gradual
      onset of bilateral resting tremor, bradykinesia and rigidity. Computerized
      tomography (CT) of the brain revealed a large parasagittal tumor in the left
      frontal lobe. The patient completely recovered from the parkinsonian symptoms
      after removal of the brain tumor. The second patient, a 74-year-old man with a
      history of renal cell carcinoma of the right kidney suffered from an insidious
      onset of bilateral bradykinesia, rigidity and gait difficulty. Cerebral
      metastasis was noted on the brain CT scan. Early recognition of intracranial
      tumor as the cause of parkinsonism is important for the management of this type
      of movement disorder. Moreover, brain CT scanning plays an important role in the
      differential diagnosis of patients with parkinsonian symptoms.

PMID- 10969455
TI  - Ticlopidine-induced severe cholestatic hepatitis.
AB  - We report a case study of an 86-year-old female patient with severe cholestatic
      hepatitis who was undergoing treatment with oral ticlopidine 250 mg daily for
      coronary artery disease. The patient had nausea and vomiting and was jaundiced
      after taking ticlopidine for 6 weeks. She was admitted to the hospital for
      further evaluation. Ultrasound and endoscopic retrograde cholangiopancreatography
      eliminated the presence of biliary obstruction. Results from a liver biopsy
      showed a histopathologic picture consistent with cholestatic hepatitis.
      Ticlopidine-induced cholestatic hepatitis has been reported 32 times in the
      foreign literature. This is the first reported severe cholestatic hepatitis
      (total bilirubin up to 43 mg/dl) case in Taiwan. Ticlopidine-related blood
      dyscrasia is a renowned adverse drug effect; liver function should be monitored
      in patients receiving ticlopidine therapy.

PMID- 10969456
TI  - Genes, viruses, and ear disease.

PMID- 10969457
TI  - Blue ear drum and cholesterol granuloma.

PMID- 10969458
TI  - Vocal fold hyperkeratosis.

PMID- 10969459
TI  - Endoscopic view of a sphenochoanal polyp.

PMID- 10969460
TI  - ENG in a woman with a history of dizziness who became nauseous and lightheaded
      while reading.

PMID- 10969461
TI  - Masticator space tumor, malignant schwannoma.

PMID- 10969462
TI  - Persistent measles virus infection as a possible cause of otosclerosis: state of
      the art.
AB  - The etiopathogenesis of otosclerosis is still largely unexplained and remains
      controversial. Morphologic examinations have shown the presence of a chronic
      inflammation in otosclerotic tissue. Among the proposed explanations for this
      inflammation are an immunologic reaction against collagen, mutations of collagen
      gene 1A1, and a viral infection. In this paper, we focus on the role of measles
      virus in otosclerosis, and we review the current literature, devoting particular
      attention to a suspected paramyxoviral etiopathogenesis in Paget's disease. Our
      examination of footplate fragments by reverse transcription polymerase chain
      reaction testing in 95 patients with otosclerosis revealed the presence of
      measles virus RNA in 83% of cases. Quantification of measles virus immunoglobulin
      G (IgG) in otosclerosis patients indicated that the ratio of antimeasles virus
      IgG in total IgG was higher in perilymph than in serum. Furthermore, an almost
      identical incidence of otosclerosis and measles virus-caused mortality in women
      suggests that women are more susceptible to measles virus infection. Finally,
      since the introduction of the measles virus vaccination program in Europe, there
      has been a decline in the incidence of otosclerosis. Moreover, the average age of
      patients at diagnosis and surgery at our hospital has increased to 54 years. Our
      findings, when they are considered along with findings regarding the presence of
      paramyxoviral RNA in Paget's disease, support the hypothesis that measles virus
      is involved in the etiopathogenesis of otosclerosis.

PMID- 10969463
TI  - First report of a case of osteoma of the larynx.
AB  - Osteomas are common in otolaryngology, as they often involve the skull and facial
      bones. On rare occasions, these tumors have also been found in the temporal bone
      and the tongue. Until now, osteomas have not been encountered in the larynx. We
      describe the case of a patient who came to our institution with hoarseness and
      dysphagia and who was found to have an osteoma of the larynx. Radiographic
      imaging, endoscopy, and pathologic classification confirmed the diagnosis. To our
      knowledge, this is the first reported case of an osteoma of the larynx.

PMID- 10969464
TI  - Combined vestibular neurectomy and endolymphatic sac shunt via the retrosigmoid
      approach in the treatment of Meniere's disease.
AB  - The nature of surgical treatment for Meniere's disease has evolved from
      destructive to conservative in the interest of preserving hearing. We have
      performed a combined procedure that involves a vestibular neurectomy to control
      vertigo, which is followed by an endolymphatic sac shunt to control hydrops in 26
      patients. Both procedures are performed via the retrosigmoid approach during the
      same surgical step. We believe this combination procedure is a worthwhile option
      to consider in order to achieve good control of vertigo and endolymphatic hydrops
      and to preserve hearing in patients with Meniere's disease.

PMID- 10969465
TI  - Sinusitis-induced enophthalmos: the silent sinus syndrome.
AB  - Enophthalmos caused by inadequate maxillary sinus function was first reported in
      1964. Since this initial report, scattered case reports and, more recently,
      reviews have appeared in the literature detailing the pathophysiology, clinical
      findings, and management of this process. We present a classic case of the
      asymptomatic development of enophthalmos caused by maxillary sinus
      hypoventilation: the silent sinus syndrome. In addition, this case included
      findings in the ethmoid sinuses that suggested their contribution to this
      disorder, which by our review of the literature has not been well described.

PMID- 10969466
TI  - The role of ultrasonography in the management of tumors of the neck.
AB  - By themselves, clinical examination and palpation do not provide an accurate
      assessment of metastatic neck nodes. They do not yield sufficient information to
      ascertain the benign or malignant nature of nodes or to determine the presence of
      extracapsular spread and vascular invasion. The use of real-time ultrasonography
      with high-frequency transducers can significantly improve the evaluation of
      patients with neck masses. We studied the use of ultrasound in evaluating
      metastatic neck disease in 25 patients. We found that it is useful not only in
      detecting neck nodes, but in assessing their characteristics and the degree of
      vascular invasion. We recommend that ultrasonography be routinely performed as
      part of the evaluation of all patients with head and neck masses. It is also
      valuable in the postoperative or postirradiation followup of patients whose necks
      are otherwise difficult to evaluate.

PMID- 10969467
TI  - Maxillary giant cell granuloma, pheochromocytoma, and hyperparathyroidism without
      medullary thyroid carcinoma.
AB  - We examined a young man who had a benign giant cell granuloma of the maxilla,
      which we subsequently diagnosed as a brown tumor associated with
      hyperparathyroidism. During surgery for the granuloma, the patient developed
      severe hypertension and was discovered to have an extra-adrenal pheochromocytoma.
      Oncogene and calcitonin testing for medullary carcinoma of the thyroid was
      negative. Therefore, despite the presence of both pheochromocytoma and
      hyperparathyroidism, we concluded that this patient did not have multiple
      endocrine neoplasia type 2a.

PMID- 10969468
TI  - Adult laryngeal hemangioma: report of four cases.
AB  - Laryngeal hemangiomas in adults are uncommon. We report four such cases seen at
      our clinic during an 18-month period in 1996 and 1997. All masses were detected
      by endoscopy, and all were biopsied and ablated uneventfully with a CO2 laser.
      All four patients recovered without incident. We feel that laryngeal hemangiomas
      that affect only the glottic area can be treated endoscopically with a CO2 laser
      without consequences.

PMID- 10969469
TI  - The vomeronasal organ: an objective anatomic analysis of its prevalence.
AB  - The function and location of the vomeronasal organ in humans remains poorly
      understood. Indeed, there has been considerable controversy as to whether it even
      exists. Until now, there has been no published report of its prevalence or
      location as ascertained by the most widely accepted visual operative instrument
      in sinonasal surgery: the rigid nasal endoscope. In this study, multiple
      observers used the nasal endoscope to determine the prevalence and character of
      the vomeronasal organ in humans. We performed nasal endoscopy on 22 cadaver heads
      and 78 live humans; we also biopsied cadaver specimens to histologically confirm
      the endoscopic diagnosis. We found evidence of this organ in 13 of the 22
      cadavers (59.1%) and in 22 of the 78 patients (28.2%). Many nasal surgeons are
      unaware of this organ and its potential physiologic significance. It is our hope
      that by recognizing its prevalence and location, nasal surgeons will be more
      likely to identify and possibly preserve this mysterious organ until its function
      is more clearly understood.

PMID- 10969470
TI  - Otomycosis: a clinicomycologic study.
AB  - Otomycosis is a common fungal infection of the ear that is seen in the tropical
      and subtropical regions of the world. We performed mycologic analyses on debris
      and scraping samples from the external ear canals of 95 patients who had been
      clinically diagnosed with otomycosis. Seventy-one samples (74.7%) were positive
      for fungal growth; two of these samples contained two fungi, bringing the total
      number of isolates to 73. The most common pathogens were Aspergillus fumigatus
      (41.1% of all isolates), A niger (36.9%), and Candida albicans (8.2%).

PMID- 10969471
TI  - Effect of tympanic perforations on the detection of distortion-product
      otoacoustic emissions.
AB  - The detection of distortion-product otoacoustic emissions (DPOAEs) depends on the
      viability of the ear's conduction apparatus. However, tympanic membrane
      perforations and other conductive disorders have not been fully investigated with
      regard to the examination of DPOAEs. Using the guinea pig model, we made
      perforations of different sizes and loci on the tympanic membrane and collected
      DPOAEs data for frequencies between 2,193 and 5,508 Hz for each condition. We
      found that small perforations, up to 25% of the area of the tympanic membrane,
      still allow us to detect emissions at the specified frequencies. However,
      perforations of 50% and larger, as well as those accompanied by traumatic
      perilymph fistulas and ossicular disarticulations, severely interfered with the
      detection of DPOAEs. We discuss the clinical relevance of these findings with
      respect to the potential uses of DPOAEs.

PMID- 10969472
TI  - Mature teratoma of the nasal vestibule: a case report.
AB  - Teratomas are rare congenital neoplasms that arise from pluripotent cells. They
      consist of tissue from all three embryonic germ layers. According to most
      studies, teratomas of the head and neck account for only 2 to 9% of all cases. In
      this article, we report the first case of a teratoma of the nasal vestibule in a
      newborn. We also discuss methods of diagnosis and treatment of upper airway
      teratomas, and we include a brief review of the literature.

PMID- 10969473
TI  - Screening for otitis media with effusion to measure its prevalence in Chinese
      children in Hong Kong.
AB  - In an attempt to gain a better understanding of the prevalence of otitis media
      with effusion (OME) in the Hong Kong community, and to compare the
      characteristics of the disease here with OME as it is described in the Western
      literature, we screened more than 6,000 6- and 7-year-old children with both
      clinical and audiologic examinations. The initial positive screening rate was
      5.3%. Upon further evaluation, we determined that the overall prevalence of
      persistent OME was 2.2%. We found that the disease pattern and natural history of
      persistent OME in Hong Kong children are similar to those reported in the Western
      literature.

PMID- 10969474
TI  - The incidence of sports-related facial trauma in children.
AB  - We conducted a survey of physician members of the American Academy of Facial
      Plastic and Reconstructive Surgery to determine the incidence and nature of
      facial traumas seen in their practices. We solicited information on the anatomic
      location of each injury, the severity of the trauma, and whether the injury
      occurred during a sports activity. According to the responses, 21% of facial
      fractures and 29% of nasal fractures were experienced by patients aged 17 years
      and younger who were participating in sports. We believe that many such injuries
      can be prevented with greater use of protective equipment.

PMID- 10969475
TI  - Factors associated with post-tonsillectomy hemorrhage.
AB  - Despite the otolaryngologist's most diligent efforts to prevent it, hemorrhage is
      the most common, albeit sporadic, significant complication of tonsillectomy. For
      this retrospective study of post-tonsillectomy hemorrhage rates, we examined the
      charts of 430 consecutive tonsillectomy patients who had been operated on by one
      of two general otolaryngologists at our institution. The two surgeons used the
      same removal technique (cold dissection and snare), but slightly different
      methods of hemostasis. We found that the overall bleeding rate was 4%; the
      primary (< 24 hr) hemorrhage rate was 0.23%, and the secondary rate was 3.7%.
      Factors that were positively correlated with postoperative bleeding were the
      patient's sex, the time of year the surgery was performed, the length of the
      procedure, the amount of blood lost during surgery, and the use of intraoperative
      vasoconstrictors and steroids. However, we believe the use of steroids can
      probably be discounted as a causative factor. The chi 2 test was used to
      determine statistical significance. None of the 21 patients who were operated on
      for peritonsillar abscess experienced any delayed postoperative bleeding. The
      mean decrease in hemoglobin was 2.3 grams; the lowest postoperative level was 6.6
      grams. The highest incidence of delayed bleeding occurred on the eighth
      postoperative day. Two patients required transfusions, and both recovered without
      any adverse consequences. It appears that one controllable variable in preventing
      delayed bleeding following tonsillectomy and adenoidectomy might be related to
      certain details of hemostatic technique. Vasoconstrictors and "field"
      cauterization might be associated with an increased temporal and spatial
      application of coagulating current. Although this technique is very effective in
      preventing primary hemorrhage, it does result in a deeper and more extensive zone
      of necrosis and the exposure of more and larger vessels when sloughing of the
      eschar occurs.

PMID- 10969477
TI  - Images of Newton.

PMID- 10969476
TI  - Laser-assisted myringotomy for otitis media: a feasibility study with short-term
      followup.
AB  - Intermediate-duration middle ear ventilation appears to be a good treatment
      option for selected children with otitis media. Laser-assisted myringotomy is one
      way to provide such ventilation. It can provide prompt pain relief and resolution
      of middle ear effusion and effusion-related hearing loss, and it can provide an
      opportunity for surveillance of antibiotic-resistant organisms. We performed
      laser-assisted myringotomy on 97 ears of 54 children over a 5-month period. All
      children had acute or recurrent otitis media or persistent middle ear effusions.
      Our experience suggests that laser-assisted myringotomy is a feasible treatment
      option for selected patients. Practitioner experience and patient and family
      considerations will contribute to the decision whether to use general or topical
      anesthesia.

PMID- 10969478
TI  - Sources for ancient science.

PMID- 10969479
TI  - Water, steam and change: the roles of land drainage, water supplies and garden
      fountains in the early development of the steam engine
AB  - The history of the steam engine is generally linked to that of the Industrial
      Revolution. This article seeks to uncouple this seemingly necessary link by
      examining other contexts in which the steam engine was introduced and developed.

PMID- 10969481
TI  - The oil palm in all our lives: how this came about
AB  - Over time, the oil palm has become the crop of central importance to both our
      daily lifestyle and to many of the great industries that man has developed.
      Remarkably, few recognize the oil palm and its fruit, and even fewer know its
      history. This article tells the story of the oil palm's rise to prominence from a
      wild plant of Equatorial Africa to becoming the most valuable plantation economy
      of the tropical world.

PMID- 10969480
TI  - The emergence of ecology from natural history.
AB  - The modern discipline of biology was formed in the 20th century from roots deep
      in the natural-history tradition, which dates from Aristotle. Not surprisingly,
      therefore, ecology can also be traced to natural history, especially its 19th
      century tradition emphasizing the adaptive nature of organisms to their
      environment. During the 20th century, ecology has developed and matured from
      pioneering work on successional stages to mathematically rich work on ecosystem
      energetics. By the end of the century, ecology has made a return to its natural
      history heritage, emphasizing the importance of the integrity of ecosystems in
      considering human interactions with the environment.

PMID- 10969482
TI  - Art as science: scientific illustration, 1490-1670 in drawing, woodcut and copper
      plate.
AB  - Observation, depiction and description are active forces in the doing of science.
      Advances in observation and analysis come with advances in techniques of
      description and communication. In this article, these questions are related to
      the work of Leonardo da Vinci, 16th-century naturalists and artists like Conrad
      Gessner and Teodoro Ghisi, and 17th-century micrographers like Robert Hooke.

PMID- 10969483
TI  - Why Darwin was English.
AB  - A 'late developer' argument, common to Psychology and Economic History, can be
      used to explain cultural innovation. It argues that the 19th century theory of
      natural selection arose in England and not Germany because of--and not in spite
      of--England's scientific backwardness. Measured in terms of institutions,
      communities, and ideas, the relative retardation of English science was precisely
      what enabled it to adopt German advances in novel ways.

PMID- 10969484
TI  - Roy Chapman Andrews and the business of exploring: cetology and conservation in
      progressive America

PMID- 10969485
TI  - HIV-1 subtypes in injecting drug users & their non-injecting wives in Manipur,
      India.
AB  - The presence of HIV-1 antibodies was determined among the injecting drug users
      (IDUs) and their non-injecting wives. A total of 233 (72%) were found to be HIV-1
      seropositive among the 322 subjects recruited in this study between August, 1996
      and September, 1997. The distribution of HIV-1 subtypes among the injecting drug
      users (IDUs) and their wives was determined using peptide enzyme immunoassay
      (EIA). Sexual transmission of HIV-1 occurred frequently (45%) from HIV-1 infected
      IDUs to their spouses. The majority of the subjects (167/233) were infected with
      subtype C followed by subtype Thai B (29/233). Subtype C was the most common
      among both IDUs (78%) and their wives (57%), followed by subtype Thai B (12% and
      13% respectively). The distribution of subtypes was significantly different
      between IDUs and their wives with a lower percentage of subtype C and higher
      percentage of subtype D in the infected wives (P < 0.03). Discordance for
      subtypes transmitted from IDUs to their wives suggests the occurrence of dual
      and/or recombinant infection in the IDUs.

PMID- 10969486
TI  - Preliminary observations on lymphocyte subpopulations in HIV seropositive & HIV
      seronegative tuberculosis patients in Pune, India.
AB  - CD4 and CD8 lymphocyte counts were determined in 59 HIV seropositive and 41 HIV
      seronegative newly diagnosed tuberculosis patients in Pune. There were
      significant differences in the CD4 counts and CD4/CD8 ratios between HIV
      seropositive and HIV seronegative tuberculosis patients. Majority of the HIV
      seropositive patients had a CD4 count less than 500 cells/cu.mm, whereas among
      the HIV seronegative patients, majority had a CD4 count more than 500
      cells/cu.mm. In HIV seropositive patients with extrapulmonary and pulmonary
      tuberculosis, the CD4 counts were lower than in those who had only pulmonary or
      extrapulmonary tuberculosis. There was no significant differences in the CD8
      counts between HIV seropositive and HIV seronegative tuberculosis patients,
      except for patients with pulmonary cavity, where the CD8 counts were
      significantly higher in HIV seropositive tuberculosis patients. In HIV
      seropositive individuals with pulmonary tuberculosis, the CD8 counts in those
      with pulmonary cavity were higher than in those without any pulmonary cavity.
      Absence of cavitation and presence of pulmonary with extrapulmonary tuberculosis
      occurred when immune activation was at a lower level.

PMID- 10969487
TI  - Prevalence of hepatitis B infection among the primitive tribes of Andaman &
      Nicobar Islands.
AB  - BACKGROUND & OBJECTIVES: Andaman and Nicobar Islands, is the home of six
      primitive tribes. No information is available on the prevalence of hepatitis B
      virus (HBV) infection among them. Hence a study was undertaken with the objective
      of assessing the sero-prevalence of HBV infection among the four accessible
      tribes of these islands. METHODS: A total of 1266 serum samples were collected
      from four tribes i.e., Nicobarese, Shompens, Onges and Great Andamanese and
      tested for the presence of HBsAg and anti-HBs. Information about different risk
      factors associated with HBV infection was also collected from the Nicobarese
      tribe. RESULTS: The overall seropositivity rate of HBsAg among the Nicobarese was
      23.3 per cent (95% C.I. 21.0-25.9). Hepatitis B was also found to be an important
      health problem among the Shompens and Onges with HBsAg positivity of 37.8 and
      31.0 per cent respectively. The age-wise distribution of these serological
      markers among Nicobarese tribe indicate that the infection is very common in all
      the age groups. The sero-prevalence was also found to be very high among the
      children. CONCLUSIONS & INTERPRETATION: The findings of the present study
      indicate that hepatitis B infection is hyper endemic among the primitive tribes
      of these islands. Though none of the risk factors studied in the Nicobarese was
      found to be significantly associated with HBV infection, the fact that almost 20
      per cent of the women in the reproductive age group were positive for HBsAg
      indicates the possibility of vertical transmission among the Nicobarese. Further
      studies are required to find out other modes of transmission.

PMID- 10969488
TI  - Role of molecular techniques in the detection of HBV DNA & HCV RNA among renal
      transplant recipients in India.
AB  - In this study we have investigated the occurrence of hepatitis B virus (HBV),
      hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among 68 renal
      transplant recipients. Replicative HBV and replicative HCV infections were seen
      in 12 (17.6%) and 38 (55.9%) patients respectively, the difference was
      statistically significant (P < 0.001). Among the 38 HCV RNA+ individuals, anti
      HCV was present only in 23. Anti-HCV in the absence of HCV RNA was detected in
      one patient. Anti-HDV antibody was seen in 2 (15.4%) of the 13 HBV infected
      individuals. Nine (13.2%) of the 68 individuals had replicative dual infection
      with HBV and HCV. Triple infection (HBV DNA+, HCV RNA+, anti-HDV+) was seen in 2
      transplant recipients. There was significantly higher demonstration of
      replicative HCV (P < 0.001) in transplant recipients having elevated liver
      enzymes (n = 34) as compared to transplant recipients having normal liver enzyme
      levels (n = 34). Though not significant, a higher detection rate was also seen
      with replicative HBV infection and replicative dual infection among transplant
      recipients with elevated liver enzymes. The higher detection of HCV in renal
      transplant recipients by molecular techniques, emphasizes the need for HCV RNA
      testing. Further deliberate attempts to change practices to reduce this problem
      may also improve graft and patient survival in recipients.

PMID- 10969489
TI  - Low rate of Japanese encephalitis infection in rural children in Thanjavur
      district (Tamil Nadu), an area with extensive paddy cultivation.
AB  - In Thanjavur district, the occurrence of Japanese encephalitis (JE) is very low
      and the district is free of epidemics. Among children aged 5-12 yr, the infection
      rates for JE in two consecutive transmission seasons of 1991-92 and 1992-93, were
      1.8 and 5.1 per cent respectively. A high cattle to pigs ratio (400:1) could
      possibly be an important factor for the low JE infection rate in children in the
      district.

PMID- 10969491
TI  - Curing children.

PMID- 10969490
TI  - Anti-keratin antibodies in patients with rheumatoid arthritis.
AB  - As the proportion of patients with rheumatoid arthritis (RA) who have anti
      keratin antibodies (AKA) varies in different ethnic groups, we studied its
      occurrence in a hospital populations with RA and its association with different
      disease variables. Sera from 84 consecutive patients with RA, 100 healthy
      controls and 85 disease controls (polyarticular juvenile rheumatoid arthritis,
      systemic lupus erythematosus, ankylosing spondylitis) were tested for AKA by an
      indirect immunofluorescence assay that used rat esophagus as substrate. The
      proportion of patients with RA who had AKA (47/84) was higher than in healthy
      controls (2/100; P < 0.001) and in disease controls (2/85; P < 0.001). The
      frequency of AKA positivity was higher among patients who had severe disease (P <
      0.05) and rheumatoid factor. Anti-keratin antibody is present in 56 per cent of
      our patients with RA and is associated with severe disease.

PMID- 10969492
TI  - Impact of genome research on children and their families.
AB  - Human genome research has made it possible to identify the presence of gene
      mutations in persons with specific genetic, conditions, who may be carriers of
      genetic disorders, or who are at risk for future development of inherited
      diseases. Gene discovery has the potential to identify individual response to
      medications and new management and preventive interventions. Pediatric nurses
      must be informed about genetic discoveries and their implications for child and
      family health to act as advocates for children and their families in all child
      health care settings.

PMID- 10969493
TI  - An international agenda for ethics in nursing and genetics.
AB  - Nurses who work with families and communities have an obligation to serve as
      advocates for ethical practices in health care that rapidly encompasses genetic
      technologies. Commercialization of gene-based diagnostics and therapies by profit
      seeking industrial biotech firms is likely to present new dilemmas for
      professionals and populations seeking control over inherited risks for illness
      for themselves and their children. This agenda presents the profession with
      challenges that infuse nursing practice, education, and research, as well as
      citizenship, on an earth with fading geopolitical boundaries and evolving
      cultural transitions.

PMID- 10969495
TI  - Learning ethics in nursing and genetics: narrative pedagogy and the grounding of
      values.
AB  - An approach to learning is proffered that simultaneously provides new ways of
      thinking about ethics and genetics. This approach, narrative pedagogy, looks
      toward the ground of ethics and values in nursing practice and genetics. The
      ground is presented here as the beginning of questioning rather than an end, that
      is, questioning as a horizon, out of which new understandings for ethics and
      genetics can emerge.

PMID- 10969494
TI  - Hereditary cancers in children and ethical and psychosocial implications.
AB  - This article describes the application of genetic testing of children for
      hereditary cancers and the resultant ethical and psychosocial implications. Basic
      cancer genetics concepts are reviewed. Specific hereditary cancers that may
      affect children are described along with case examples and recommendations for
      nursing practice.

PMID- 10969497
TI  - Genetics of cleft lip and palate.
AB  - Cleft lip with or without cleft palate (CL/CP) is one of the most common
      structural birth defects, with treatment including multiple surgeries, speech
      therapy, and dental and orthodontic treatments over the first 18 years of life.
      As a result of the treatment interventions, pediatric nurses may be required to
      care for these children beginning in infancy through adolescence. Providing care
      for these patients and families can include educating patients and parents about
      the genetics of CL/CP, as well as meeting their immediate medical needs. A basic
      overview of normal lip and palate development, classification of clefts,
      pathophysiology of CL/CP, incidence, inheritance, genetic and environmental
      causes, genetic counseling, prenatal diagnosis, fetal surgery, and nursing
      implications is provided to educate pediatric nurses about the basics of the
      genetics of CL/CP.

PMID- 10969496
TI  - Mitochondrial disease: beyond etiology unknown.
AB  - Mitochondrial dysfunction is now recognized as a relatively common cause of
      degenerative disease in children. Mutations in either the mitochondrial or the
      nuclear genome that cause errors in the synthesis of enzymes essential for energy
      production and metabolism lead to a wide variety of pediatric problems, including
      developmental delays, sensorimotor impairment, seizures, diabetes, and organ
      failure. This article reviews the role of mitochondria in health and illness,
      discusses the clinical aspects of mitochondrial dysfunction, describes the
      experiences of three children with mitochondrial disease, and presents nursing
      strategies for affected families.

PMID- 10969498
TI  - The physical activity and fitness of our nation's children.

PMID- 10969499
TI  - The human spirit: growing up with a chronic illness.

PMID- 10969500
TI  - Compliance of adolescents with diabetes.
AB  - The purpose of this article is to describe the compliance of adolescents with
      diabetes and some factors connected to it. Altogether, 300 individuals aged 13 to
      17 years were randomly selected from the Finnish Social Insurance Institution's
      register. Every fifth person on the list was included in the sample. Ninety-seven
      percent (N = 289) of the adolescents with diabetes returned the questionnaire.
      The data were analyzed by using the Statistical Package for the Social Sciences
      (SPSS) software. Only about one fifth (19%) of the respondents with diabetes felt
      that they complied fully with the health regimens, whereas 75% placed themselves
      in the category of satisfactory compliance and the remaining 6% reported poor
      compliance. Compliance with home monitoring was poorest: Only 25% said they fully
      complied with the home monitoring instructions, and 51% showed poor home
      monitoring compliance. The highest degree of compliance was reported for insulin
      treatment, with 81% of the patients ranking in the top category. Some
      statistically significant (p < .001) relationships between the degree of
      compliance and the background variables, such as the duration of disease;
      exercise; smoking; alcohol intake; and serum glycosylated hemoglobin (GHbA1c)
      value, were found. Good motivation, a strong sense of normality, energy and
      willpower, support from parents; physicians; and nurses, a positive attitude
      toward the disease and its treatment, no threat to one's social well-being, and
      fears of complications explained good compliance (p < .001).

PMID- 10969501
TI  - Magnetic resonance imaging assessment of left ventricular function and wall
      motion.
AB  - Assessment of left ventricular (LV) function is essential for the diagnosis and
      treatment of cardiac patients. A reliable and noninvasive tool for quantifying
      global and local LV function is needed. Magnetic resonance (MR) imaging has
      several unique features that are well suited to clinical examinations: it is
      noninvasive, does not expose the patient to ionizing radiation, and provides
      images of high spatial resolution and excellent soft tissue contrast without the
      need for contrast medium injection. In this paper, I review the reported evidence
      concerning the validity of MR imaging assessment of LV volume, including end
      diastolic volume, end-systolic volume, and ejection fraction, and the validity of
      using MR imaging to monitor LV wall motion. Abundant evidence from phantom,
      animal, and human studies supports that MR imaging provides accurate and
      reproducible information that is substantially superior to that from conventional
      modalities such as angiographic ventriculography, radionuclide scintigraphy, and
      echocardiography. A fast MR imaging technique, cine MR imaging, further enhances
      the clinical feasibility of MR imaging by reducing the scanning time to about 20
      minutes. Today, cine MR imaging is widely accepted as a reliable clinical tool.
      It may be considered an in vivo standard for quantification of LV volume and wall
      motion. Faster MR imaging techniques, such as TurboFLASH and echo-planar imaging,
      decrease the examination time to several seconds. This allows evaluation of
      transient functional changes during pharmacologically or physically induced
      stress tests.

PMID- 10969502
TI  - Effects of VEGF121 and/or VEGF165 gene transfection on collateral circulation
      development.
AB  - BACKGROUND AND PURPOSE: Angiogenesis is regulated by various factors, including
      vascular endothelial growth factor (VEGF). Five isoforms of VEGF have been
      discovered: VEGF121, VEGF145, VEGF165, VEGF189, and VEGF206. The teleologic basis
      for the various VEGF isoforms remains unclear, but different VEGF isoforms may
      mediate distinct endothelial cell functions such as angiogenesis, vascular
      permeability, and differentiation. We sought to determine the effects of various
      VEGF isoforms on angiogenesis under ischemic conditions in rabbits. METHODS: The
      effects of VEGF121 and/or VEGF165 gene transfection on collateral circulation
      development in ischemic rabbit hindlimb muscles were investigated by using naked
      plasmids encoding VEGF121 or VEGF165 (pVEGF121 or pVEGF165), either individually
      or in combination. pCMV beta was used as the control plasmid. The femoral artery
      on one side of New Zealand White rabbits was ligated. Ten days later, the
      ischemic muscles received direct intramuscular injection of pVEGF121 (500
      micrograms), pVEGF165 (500 micrograms), or pVEGF121 (250 micrograms) + pVEGF165
      (250 micrograms) in experimental groups, while pCMV beta (500 micrograms) was
      used in the control group. Therapeutic effects were evaluated 30 days later by
      anatomic and physiologic analysis. RESULTS: Internal iliac angiography showed
      strong development of collateral circulation in all of the pVEGF-treated groups.
      In contrast, collateral arteries developed weakly in the control group.
      Combination treatment with both pVEGF121 and pVEGF165 did not result in
      additional improvement compared with pVEGF121 or pVEGF165 treatment alone
      (angiographic scores: pVEGF121 = 0.85 +/- 0.10; pVEGF165 = 0.81 +/- 0.11;
      pVEGF121 + pVEGF165 = 0.83 +/- 0.09; control = 0.53 +/- 0.09; p < 0.01). A
      favorable response in the development of circulation at the capillary level with
      pVEGF121 and/or pVEGF165 versus pCMV beta was also found. Blood pressure
      measurement and regional blood flow measurement using colored microspheres
      revealed similar results. CONCLUSIONS: Our results show that direct intramuscular
      injection of naked DNA encoding VEGF121 or VEGF165, individually or in
      combination, is an effective method for gene transfer in an animal model of
      ischemic limbs and results in augmented collateral vascular development and
      tissue perfusion.

PMID- 10969503
TI  - Bacteremia due to Campylobacter species: high rate of resistance to macrolide and
      quinolone antibiotics.
AB  - BACKGROUND AND PURPOSE: Although the rate of isolation of Campylobacter from
      stool specimens in Taiwan is similar to those in other developed countries,
      Campylobacter bacteremia has rarely been reported in Taiwan, and the patterns of
      antimicrobial susceptibility of blood isolates to various antimicrobial agents
      remain unknown in the Taiwanese population. The purpose of this study was to
      determine the clinical characteristics of patients with Campylobacter infection
      in a university hospital in Taiwan and the antimicrobial susceptibility patterns
      of the Campylobacter isolates. METHODS: We retrospectively reviewed medical
      records of all patients with Campylobacter bacteremia treated in a university
      hospital between January 1991 and March 1999. Minimum inhibitory concentrations
      of 13 antimicrobial agents to 10 stored blood isolates were determined using the
      E-test. RESULTS: Approximately half (52%) of the 21 patients had chronic liver
      disease and one-quarter had hepatobiliary or gastrointestinal malignancies.
      Thirteen (62%) patients had conditions that were associated with gastroenteritis.
      Other clinical manifestations associated with Campylobacter infection included
      cellulitis, perinatal sepsis, peritonitis, vascular catheter-related infection,
      and primary bacteremia. The duration of illness was generally short:
      approximately half (52%) of the 21 patients had fever lasting for only 1 day.
      Antimicrobial susceptibility testing of the 10 isolates revealed that most of the
      blood isolates were resistant to erythromycin and nalidixic acid (100% and 90%,
      respectively), while the rate of cross-resistance between erythromycin and
      azithromycin was 70%, and that between nalidixic acid and ciprofloxacin was 67%.
      CONCLUSIONS: Our observations suggest that Campylobacter bacteremia should be
      included in the differential diagnosis of patients with chronic liver disease or
      malignancies involving the hepatobiliary system or gastrointestinal tract who
      present with fever and gastroenteritis. Clinicians in Taiwan should be alert to
      the high rate of resistance of Campylobacter isolates to macrolide and quinolone
      antibiotics.

PMID- 10969504
TI  - Flexible bronchoscopic diagnosis of airway injuries after intubation in children.
AB  - BACKGROUND: Airway intubation injuries occur frequently but are often neglected
      because of spontaneous regression. Although most airway injuries that result from
      intubation resolve without sequelae, severe complications can develop even when
      initial symptoms of upper airway obstruction are absent. This retrospective study
      assessed the clinical features, flexible bronchoscopic findings, and clinical
      outcomes in children with airway intubation injuries. METHODS: From February 1998
      to February 1999, 90 children underwent flexible bronchoscopic examination in our
      hospital. Fifteen of these patients (6 girls, 9 boys; age range, 1 mo to 5 yr;
      mean, 21.1 +/- 24.4 mo) were noted to have intubation injuries. RESULTS: The
      average time for symptoms to emerge after extubation was 1.8 days (range, 0-14
      days). The airway intubation injuries diagnosed by flexible bronchoscopy were
      subglottic stenosis in seven patients, vocal cord granulation in four,
      supraglottic granulation in two, subglottic web in two, bronchial granulation in
      two, glottic stenosis in one, and tracheal stenosis in one; two cases were
      discovered incidentally during postoperative follow-up. Four patients had
      undergone repeated intubation and eventually required tracheostomy. CONCLUSIONS:
      The results of this study indicate that flexible bronchoscopy is a simple, safe,
      and useful technique for the diagnosis and follow-up of airway intubation injury.
      It should be performed on all patients who have symptoms of upper airway
      obstruction after extubation as well as those who have undergone long-term or
      emergency intubation.

PMID- 10969505
TI  - Efficacy and safety of methotrexate therapy for juvenile rheumatoid arthritis.
AB  - BACKGROUND AND PURPOSE: Juvenile rheumatoid arthritis (JRA) can result in
      disability, growth disturbance, and systemic complications. This study
      investigated the efficacy and adverse effects of oral methotrexate (MTX) therapy
      in Taiwanese children with JRA. METHODS: The medical records of 52 Taiwanese
      children with JRA treated with oral MTX were retrospectively analyzed. The
      disease onset was polyarticular in 22 children, oligoarticular in 13, and
      systemic in 17. The indication for MTX therapy was lack of efficacy of previous
      drugs, including two or more nonsteroidal anti-inflammatory drugs, in all
      patients. In addition, three patients had received hydroxychloroquine and one had
      received sulfasalazine, without improvement. Corticosteroid dependency had
      developed in 27 patients prior to MTX therapy. The mean initial dose of MTX was
      9.1 mg.m-2.wk-1 (range, 5-20 mg.m-2.wk-1), and the mean maximal dose was 10.2
      mg.m-2.wk-1 (range, 5-20 mg.m-2.wk-1). The mean duration of treatment was 23
      months (range, 6-96 mo), and the mean duration of follow-up was 52 months (range,
      10-123 mo) from the start of MTX therapy. RESULTS: Thirty-six children (69%)
      showed clinical improvement and 25 children (48%) achieved clinical remission.
      The administration of MTX resulted in more than a 50% reduction in required
      corticosteroid dosage in six children, and complete discontinuation of
      corticosteroid in 10 children. MTX was discontinued in 18 patients following a
      mean of 8 months (range, 2-34 mo) of clinical remission. Relapse occurred in nine
      (50%) of these patients. Thirteen patients (25%) suffered from adverse effects
      associated with MTX treatment. All of these adverse effects resolved
      spontaneously, or subsided within 4 weeks following dosage reduction or
      discontinuation of MTX. CONCLUSIONS: Oral MTX therapy is effective and well
      tolerated in Taiwanese children with JRA. It can serve as the first choice of
      second-line therapy in JRA.

PMID- 10969506
TI  - Ethambutol retinal toxicity: an electrophysiologic study.
AB  - BACKGROUND AND PURPOSE: In animal studies, ethambutol (EMB) has been shown to be
      toxic to cone pedicles and to cause their degeneration in the retinas of fish.
      The purpose of this study was to determine whether EMB is toxic to retinas in
      humans. METHODS: Twenty-seven patients with EMB-induced optic neuropathy and 20
      normal control subjects were included in this study. The following details were
      recorded: age, sex, and systemic condition of the patients, daily dosage of EMB,
      duration of EMB treatment, visual function at the time of electrophysiologic
      investigation, time from the onset of blurred vision to the discontinuation of
      EMB treatment (symptom duration), and time from termination of EMB treatment
      until electrophysiologic investigation. RESULTS: The electroretinograms were
      normal in 25 patients. Twelve patients had normal electro-oculogram (EOG)
      findings in both eyes and the remaining 15 patients had abnormal EOG findings in
      at least one eye. Ten eyes showed supranormal EOG (light/dark (L/D)) ratios of
      more than 2.33, and 13 eyes had decreased L/D ratios (< 1.65). The symptom
      duration was shorter in the supranormal EOG group. CONCLUSIONS: The results
      suggest that a supranormal EOG may be indicative of an early toxic state during
      EMB therapy and that EMB may cause dysfunction of the retinal pigment epithelium.

PMID- 10969507
TI  - Wound healing patterns following perforation sustained during laser in situ
      keratomileusis.
AB  - BACKGROUND AND PURPOSE: Corneal perforation during laser in situ keratomileusis
      (LASIK) may interfere with flap adhesion and wound healing. The purpose of this
      study was to investigate wound healing patterns following corneal perforation
      sustained during LASIK in rabbits. METHODS: Forty-two pigmented rabbit eyes
      underwent LASIK surgery with 5.0-mm excimer laser treatment under the corneal
      flap. Animals were divided into two groups: group I (n = 19) underwent the
      regular LASIK procedure with -10.0 D treatment, without perforation; in group II
      (n = 23), the cornea was perforated with the excimer laser. Treatment was
      discontinued once perforation was observed, and the corneal flap was replaced
      without sutures. Slit-lamp biomicroscopy, photography, and scatterometry were
      performed preoperatively and at 1 and 2 days, 1 week, and weekly up to 1 month, 2
      months, and 3 months postoperatively. Animals were killed at 1 day, 1 week, 1
      month, and 3 months postoperatively and processed for light microscopic, electron
      microscopic, and immunohistochemical examinations. RESULTS: In group I, the
      corneas remained clear throughout the experiment. In all eyes, the interface was
      not readily discernable clinically or histologically. Corneal wound healing was
      accompanied by minimal cell infiltration. Epithelial hyperplasia at the flap edge
      was noted at 1 week. Myofibroblast activation was found at the epithelial wedge
      where there was an epithelial basement membrane break. In group II, the anterior
      chamber was shallow with no iris incarceration at the end of surgery. The corneas
      were clear (n = 6) or showed mild to moderate edema (n = 12). Corneal edema
      peaked at 3.6 +/- 5.0 days and subsided thereafter. Corneal wounds healed
      similarly to those in group I except at the perforation site. The break in
      Descemet's membrane and endothelium was covered with a fibrin plug on day 1,
      which resolved thereafter. There was no statistically significant difference in
      the incidence of postoperative infection (p = 1.0) or flap displacement (p =
      0.69) rates between the two treatment groups. The scatterometry index peaked at 2
      to 3 weeks postoperatively and was significantly higher in group II than in group
      I (p < 0.001). CONCLUSIONS: Although corneal perforation during LASIK surgery may
      interfere with immediate postoperative flap adhesion, corneal wound healing
      following LASIK perforation may be similar to that after an uncomplicated LASIK
      procedure.

PMID- 10969508
TI  - Propylthiouracil-induced antineutrophil cytoplasm antibody-positive anaphylactoid
      purpura-like vasculitis--a case report.
AB  - Propylthiouracil (PTU), a drug commonly used for treatment of hyperthyroidism, is
      associated with various rare side effects. Antineutrophil cytoplasm antibody
      (ANCA)-positive vasculitis is a relatively unusual complication among them. The
      pathogenesis of ANCA-positive vasculitis during PTU therapy is still obscure. We
      present the case of a 12-year-old boy who developed ANCA-positive vasculitis
      during PTU therapy for Graves' disease. His symptoms and signs were
      indistinguishable from anaphylactoid purpura, a common small-vessel vasculitis in
      children. The clinical manifestations improved after discontinuation of PTU and
      immunosuppressant treatment. He remained symptom-free at 11-months follow-up.

PMID- 10969509
TI  - Subungual squamous cell carcinoma: report of 2 cases.
AB  - Subungual squamous cell carcinoma (SCC) is a rare malignant tumor with an
      indolent course. Its etiology is unknown. It often involves the distal phalanx of
      the thumb or the index finger, and often presents as a chronic ulcer that is
      commonly misdiagnosed as chronic paronychia, pyogenic granuloma or verruca
      vulgaris. Approximately 150 cases of subungual SCC, including one in a Taiwanese
      patient, have been reported. Here, we report two cases of subungual SCC
      presenting as a chronic ulcer of the nail bed refractory to antibiotic treatment.
      One case involved the right thumb, while the other involved the right index
      finger. Radiographs of both cases showed an osteolytic bone lesion involving the
      distal phalanx. Excision biopsy revealed SCC in both cases. Both patients
      received amputation of the involved distal phalanx and showed no signs of
      reoccurrence during 5 years of follow-up. These findings suggest that all
      recalcitrant ulcers of the nail bed should be biopsied to facilitate early
      diagnosis and treatment of subungual SCC.

PMID- 10969510
TI  - Enteric mucocele formation after endorectal pull-through: report of a case.
AB  - We report a case of enteric mucocele formation in a 4-year-old boy after
      endorectal pull-through correction for Hirschsprung's disease with proximal
      intestinal neuronal dysplasia. On 17 April 1997, when the patient was 2 years
      old, a loop ileostomy was performed after an ineffective endorectal pull-through
      operation involving the right colon. Because of frequent prolapse of the stoma,
      when the child was two-and-a-half years old an end ileostomy was made by a
      resection of the distal ileotoma and redundant terminal ileum. When he was 4
      years old, he was readmitted because of ileus, peritonitis, and a huge abdominal
      mass. Complete atresia of the colon at the level of pelvic reflection with
      proximal enteric mucocele formation was noted at laparotomy. He made an
      uneventful recovery after resection of the mucocele. This is the first reported
      case of such a complication after an endorectal pull-through operation. The
      possible causes and techniques for the prevention of this complication are
      discussed.

PMID- 10969511
TI  - Transient topographical disorientation as a manifestation of cerebral ischemic
      attack.
AB  - Topographical disorientation (TD) is rare, especially as a manifestation of
      transient ischemic attack. Here, we report a case of transient TD as a
      manifestation of cerebral ischemic attack. A 55-year-old male bus driver suffered
      from sudden inability to recognize familiar surroundings. He completely recovered
      from this within 12 hours, but suffered a second episode of TD 3 weeks later, in
      combination with visual agnosia and prosopagnosia. Cerebral magnetic resonance
      imaging and single-photon emission computed tomography showed a lesion that had
      recently developed in the right posterior cerebral artery, in addition to a
      previous lesion in the left occipital pole. His TD symptoms persisted after the
      second episode.

PMID- 10969512
TI  - Prolonged neuromuscular block with mivacurium in a patient with cholinesterase
      deficiency.
AB  - Mivacurium is a short-acting, nondepolarizing neuromuscular blocking agent
      hydrolyzed by plasma cholinesterase. Because it allows fast recovery, it is a
      commonly used muscle relaxant for patients undergoing short surgical procedures.
      We report the case of a 5-year-old boy who underwent outpatient inguinal
      herniorraphy and developed unexpected prolonged neuromuscular block after the use
      of mivacurium. He required mechanical ventilation support in the intensive care
      unit because he could not attain adequate muscle power 1 hour after termination
      of anesthesia; the muscular paralysis persisted for 5 hours after the bolus dose
      of 0.3 mg/kg mivacurium. Subsequent investigation revealed an extremely low
      plasma cholinesterase concentration (115 U/L), and this was later determined to
      be a congenital condition. This is the first reported case of cholinesterase
      deficiency diagnosed as a result of general anesthesia in Taiwan.

PMID- 10969513
TI  - Home-based patient-controlled epidural analgesia with bupivacaine for patients
      with intractable herpetic neuralgia.
AB  - This clinical report is based on retrospective observation of the outcome and
      effects of patient-controlled epidural analgesia (PCEA) with bupivacaine infusion
      administered at home to five patients with intractable herpetic neuralgia. All
      patients had severe pain (9 or 10 visual analogue scale [VAS]points) confined to
      the affected dermatomes, which was refractory to medication. The interval between
      zoster onset and PCEA application ranged from 27 to 60 days (mean, 37.2 d). The
      average daily amount of bupivacaine used was 36.5 to 91.2 mg (mean +/- standard
      deviation, 62.4 +/- 19.7 mg). The duration of PCEA therapy ranged from 10 to 28
      days (18.4 +/- 7.6 d). One patient developed drug tolerance. All treatments
      resulted in effective and satisfactory pain relief (VAS, 0-3), with increase in
      physical activities to normal levels and easing of sleep and appetite impairment.
      No deleterious effects were found during PCEA therapy. After discontinuation of
      PCEA, two patients did not complain of pain but still had slight paresthesia, one
      of them required low-dose antidepressant for 17 days; three patients continued to
      have occasional sharp pain (VAS, 2-3) and required low-dose antidepressant and
      analgesic as-needed for one to six months. These results suggest that PCEA with
      bupivacaine infusion provides effective pain relief in patients with intractable
      herpetic neuralgia and is a feasible and effective home treatment modality with
      limited side effects.

PMID- 10969514
TI  - Consumer health information websites in Taiwan.
AB  - Developers of consumer health information (CHI) websites and pages in Taiwan have
      included: 1) individuals; 2) general hospitals; 3) disease-oriented associations;
      4) government health administrative agencies; and 5) commercial corporations.
      General hospitals have developed the largest number of sites, but the quality of
      these sites differs widely. The unprecedented impact of health-oriented websites
      on medical care and the health of the public in general necessitates the
      establishment of credible instruments for the evaluation and rating of the
      quality of such websites and pages. In this paper, we describe the current status
      of CHI websites and pages in Taiwan. Suggestions for improving the content of CHI
      websites and pages are also proposed.

PMID- 10969515
TI  - Castleman's disease.

PMID- 10969516
TI  - Medicare 1966-2000. 1966.

PMID- 10969517
TI  - Scanning laser polarimetry in evaluation of retinal nerve fiber layer thickness
      for normal Taiwanese.
AB  - Scanning laser polarimetry has been used recently for the measurement of retinal
      nerve fiber layer (RNFL) thickness, taking advantage of the birefrigence of the
      RNFL. We observe the RNFL with the instrument and try to find out a set of normal
      basic values of the RNFL thickness for clinical comparison. One hundred normal
      volunteers of different age groups were recruited for this study. There are 44
      males and 56 females with a mean (1SD) age of 36.17(14.77) years. Three
      consecutive 15-degree polarimetric maps were acquired for each subject. RNFL
      thickness measurements were obtained at 1.75 disc diameters ring from the optic
      nerve. Four 90-degree quadrants were identified. As a result, the average of RNFL
      thickness is 90.69 (20.20) microns in the superior quadrant, 80.45 (17.4) microns
      in the inferior quadrant, 59.28 (15.37) microns in the nasal quadrant, and 48.98
      (15.72) microns in the temporal quadrant with a mean thickness value of 69.86
      (13.97) microns. Superior and inferior quadrants showed a comparatively thicker
      nerve fiber layer than nasal and temporal quadrants. The temporal quadrant was
      always the lowest. The axial length does not affect the RNFL thickness and no
      significant difference between males and females exists. However, an obvious
      inverse linear correlation between age and the RNFL thickness in all quadrants is
      found. The average RNFL thickness decreased with age by 0.26 micron per year. (R2
      = 0.081, p-value = 0.004). When compared with the normal range, age-match would
      be necessary.

PMID- 10969518
TI  - The DCC protein expression in breast carcinoma.
AB  - Inactivation of the gene "deleted in colon cancer" (DCC) on chromosome 18 is
      known to be associated with the tumorigenesis and metastasis of colorectal
      cancer. In the present study, we investigated the expression of DCC, P53 and HER
      2/neu product in surgical specimens from 79 patients with invasive breast cancer
      by immunohistochemistry staining and found the expression of DCC to be decreased
      in 42 tumors (52%). Overexpression of HER-2/neu and P53 was detected in 29
      (36.8%) and 26 (32.9%) of this 79 breast cancer specimens, respectively. To
      evaluate the outcomes of the 79 breast cancer patients, we followed up the
      patients during the period from May 1990 to August 1998. The average length of
      follow-up was 52 months (ranging from 4 to 94 months). Patients with tumors
      having a combination of DCC-negative and HER-2/neu overexpression showed a
      marginal influence on survival time of breast cancer (P = 0.06). However,
      patients with tumors having a combination of DCC-negative and P53 overexpression
      showed no influence of these on survival time of breast cancer (P = 0.36). These
      findings suggest that a decreased DCC expression and HER-2/neu overexpression may
      influence the prognosis of breast cancer.

PMID- 10969519
TI  - A novel approach of intravenous electrocardiograph technique in correct position
      the long-term central venous catheter.
AB  - Intravenous electrocardiograph (IVECG) can correctly positioning the catheter tip
      by enlarging p wave as it is moved toward right atrium, and it is a safe,
      reliable and accurate technique. To evaluate the efficacy of wire-conducted IVECG
      signal and IVECG signal from the port with sodium bicarbonate (NaHCO3) flushed
      catheter and to compare those with conventional anatomy landmark method was the
      propose of this study. This prospective study was carried out in 216 patients who
      suffered from malignant diseases. The correct position of the catheter tip among
      these groups was confirmed as follows. In group 1 (n = 80), the anatomy landmark
      method and portable chest radiograph recognized the correct position. In group 2
      (n = 72), IVECG signal was conducted from guide wire to identify the tip
      position. In group 3 (n = 64), IVECG signal was conducted from the port with
      NaHCO3 (0.8 mEq/mL) flushed catheter to ascertain the tip position. The patient
      characteristics did not differ significantly among the groups. The duration of
      operation was significantly (P < 0.001) longer in group 1 than in group 2 and
      group 3 (45.4 +/- 9.3 minutes vs 35.7 +/- 8.0 minutes and 35.2 +/- 9.7 minutes,
      respectively). Catheter tip placement times were shorter in group 2 and group 3
      than in group 1 (5.3 +/- 2.9 minutes and 6.4 +/- 3.0 minutes vs 16.7 +/- 5.7
      minutes, respectively); there was a statistically significant difference between
      the group 1 and group 2 and group 3 (p < 0.001). Nonetheless, the duration of
      operation and catheter tip placement time was similar in group 2 and group 3.
      Early and late complications within the subsequent 3 months showed no significant
      difference among groups. We concluded that IVECG signal conducted from guide wire
      obtained a similar efficiency to that signal from the port with NaHCO3 flushed
      catheter on positioning the catheter tip of the venous Port-A-Cath system. It is
      recommended to use these methods to facilitate implanting long-term central
      venous devices.

PMID- 10969520
TI  - The strength and functional performance in patients with facioscapulohumeral
      muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive myopathy
      with autosomal dominant inheritance remarkable for its early involvement of
      facial musculature. The purpose of our study was to assess the rate of strength
      deterioration, functional condition and performance of activity of daily living
      of patients with FSHD in Taiwan. Twenty patients diagnosed with FSHD were
      included in this study. Manual muscle testing (MMT) was used to evaluate muscle
      strength. The Brooke and Vignos scales were used to assess upper and lower
      extremity function respectively, and the capability of the activity of daily
      living was measured by Barthel index. The result of the strength testing was
      characterized by the presence of a progressive asymmetrical muscular weakness in
      patients with FSHD. The mean muscular strength of the right extremity was weaker
      than its left counterparts (p < 0.05) and the shoulder muscle group was the
      weakest. According to the Brooke functional scale, 20% of our patients were
      graded as 1, 30% as grade 2, and 50% as grade 3. On the Vignos functional scale,
      50% of patients fell into grade 1, 10% in grade 2, and 40% in grades 3-5. Vignos
      scale was significantly correlated with mean muscle strength (p < 0.05). The
      average value of Barthel index was 97.8 +/- 4.7. The muscle strength decline in
      this Taiwanese of FSHD population was more severe in shoulder girdle area. The
      mean muscle strength of the right extremity was weaker than the left. Most of our
      patients suffered from mild or moderate physical disability. Finding of these
      Taiwanese FSHD population is similar to those reported elsewhere in the world.

PMID- 10969521
TI  - Influences of tramadol on emergence characteristics from sevoflurane anesthesia
      in pediatric ambulatory surgery.
AB  - Sevoflurane is used for pediatric ambulatory surgery due to its low blood
      solubility, rapid emergence, non-pungency and low airway irritability.
      Nevertheless, its tendency to induce agitation during emergence may offset its
      benefits. The following study was designed to evaluate the effects of intravenous
      (i.v.) tramadol (1 mg/kg) on the emergence from sevoflurane anesthesia. Forty ASA
      I children, ranging from 1 to 8 years old, scheduled for inguinal surgery, were
      randomized into two groups (Group S--control group, Group ST--i.v. tramadol, 20
      in each group). The patients were first premedicated with oral atropine (0.01
      mg/kg), then anesthesia was induced with i.v. application of thiamylal (3-4
      mg/kg) and maintained with mask anesthesia with sevoflurane. Topical infiltration
      with 2-3 ml of 1% lidocaine was applied over skin incision area. I.v. tramadol (1
      mg/kg) was given before the end of operation in Group ST. The emergence agitation
      was recorded on a visual analog scale (VAS, 0-10) by a blinded anesthesiologist
      in the PACU (postoperative anesthesia care unit), as well as the length of other
      recovery stages and complications after anesthesia. The age, weight, gender, and
      duration of surgery and anesthesia were similar in the two groups. The emergence
      agitation score (6.3 +/- 3.5 vs. 3.2 +/- 2.8, P < 0.05), incidences of agitation
      (VAS > 5, 55% vs 20%, P < 0.05), and postoperative pain (65% vs 30%, P < 0.05)
      were higher for the control group. I.v. Tramadol (1 mg/kg) before the end of
      operation reduced postoperative pain and the incidence and degree of emergence
      agitation from sevoflurane anesthesia in pediatric ambulatory surgery.

PMID- 10969522
TI  - Desmoplastic small round cell tumor--report of 3 cases and review of the
      literature.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare neoplasm with distinctive
      histological features, characterized by extensive stromal tissue around islands
      of small and undifferentiated cells revealing the desmoplastic appearance. It was
      first described by Gerald and Rosai. It mainly the peritoneum and is found
      predominently in adolescents and young adults, and it is much more common in
      males than in females. The histological and immunhistochemical features are very
      distinct but may be misdiagnosed as other undifferentiated neoplasm if the
      pathologist has no idea of this entity. We report the experience of three cases
      here. The first case was diagnosed as malignant neuroendocrine neoplasm orginally
      and revised to DSRCT later. Case 2 had been diagnosed as Atypical carcinoid and
      received surgery and chemotherapy. It was revised as DSRCT 5 years later by an
      other pathologist. Case 3 carried the characteristic feature whereby diagnosis
      could be made even in frozen section.

PMID- 10969523
TI  - Choroidal retinal anastomosis in age-related macular degeneration as demonstrated
      by fluorescein angiography--a case report.
AB  - Pathological choroidal retinal anastomosis is relatively rare. It has been
      described in age-related macular degeneration (AMD) with fibrous scarring or
      occult pigment epithelial detachment or actively proliferating classic choroidal
      neovascular membrane (CNV). We report a case of disciform macular scar with the
      occurrence of a choroidal retinal anastomosis, which directed blood flow from an
      occult choroidal neovascular membrane into a retinal vein through the fovea in a
      52-year-old female with unilateral AMD. Fluorescein angiography (FA) clearly
      demonstrated the anastomosis.

PMID- 10969524
TI  - Pulmonary strongyloidiasis--case report of 2 cases.
AB  - Strongyloidiasis is a benign gastrointestinal infection. It can pass through the
      lungs and induce pulmonary strongyloidiasis. The suspicion of pulmonary
      involvement begins with clinical and chest radiographic features in the patients
      at risk. They are as follows: chronic lung diseases, age was 65 years, altered
      cellular immunity, and use of corticosteroids. Definitive diagnosis is made by
      identification of strongyloides in the secretion or tissue of the respiratory
      tract. We present 2 patients with pulmonary strongyloidiasis in this research.
      These 2 cases were patients with chronic obstructive pulmonary disease; both
      patients were more than 65 years old. They had the risk factors for severe
      strongyloides infection (advanced age, use of corticosteroids, an high serum
      cortisol level), worsening of pulmonary symptoms (e.g., dyspnea, cough, sputum
      production) and abnormal radiographic findings. Strongyloides stercoralis was
      found in the sputum and stool, and pulmonary strongyloidiasis was diagnosed.
      Mebendazole 100 mg twice daily was used and this eliminated the parasite from the
      stool in case 1, and from the sputum in case 2. Unfortunately, there was a
      relapse of parasite infection in case 1 and it also induced pulmonary
      strongyloidiasis. Finally, he died of respiratory failure. Since this disorder
      has a high relapse rate (15%), serial follow-up of stool and sputum is very
      important.

PMID- 10969525
TI  - Scientific innovation will solve the looming healthcare crisis.

PMID- 10969526
TI  - Development and quantification of H2O2 decontamination cycles.
AB  - Whereas correlation of physical process parameters with bacterial reduction is
      well established in thermal sterilisation, such a method is currently neither
      generally recognised nor possible for H2O2 decontamination. As a result, the
      efficiency and reproducibility of H2O2 decontamination and the course of the
      process over time can at present only be ascertained, verified, and documented
      using a microbiological system. Based on the "Fractional Negative" method of
      determining the D-values of Biological Indicators (BIs), which is contained in
      the ISO 11138-1 and EN 866-3 standards, a complete and systematic method is
      presented that enables the parameters for each cycle phase to be determined and
      verified, and the effectiveness of the process to be quantified. The method also
      enables differences in bacterial reduction between positions which can be
      effectively decontaminated and "worst case" positions to be quantified, so that,
      using the results, the process can be individually adjusted to specific overall
      bacterial reduction requirements. The new method also specifies the procedure for
      assessing the suitability of the microbiological system used prior to
      qualification and validation a condition sine qua non if process parameter
      studies are to be used to establish and document a decontamination cycle. With
      the aid of practical experimental data, this paper presents in detail the
      individual stages involved in the method proposed for decontamination cycle
      development, and interpretation of the results and their implications for the
      process parameters. In particular, it is shown that bacterial reduction is only
      stable over time under certain conditions, and that doubling the decontamination
      time does not result in doubling of kill effect. Moreover, the method makes it
      possible to react to any fluctuations in resistance in the microbiological system
      employed, which occur during requalification of the process.

PMID- 10969527
TI  - Pharmaceutical container/closure integrity. VI: A report on the utility of liquid
      tracer methods for evaluating the microbial barrier properties of pharmaceutical
      packaging.
AB  - The relationship between a liquid tracer package leak test (Mg ion ingress) and
      microbial immersion challenge test was demonstrated by direct and indirect
      correlation techniques. Rubber-stoppered glass vials with micropipette leaks were
      evaluated by a helium leak rate method, filled with broth, sterilized, and
      immersed in a bath containing microorganisms (E. coli/B. diminuta) and liquid
      tracer (Mg ions). After exposure and incubation, each unit was evaluated for
      liquid tracer ingress by atomic absorption spectrophotometry and for microbial
      ingress by visual inspection and blood agar streaking. Two hundred and eighty
      sterile broth-filled test units were challenged with microorganisms and liquid
      tracer. One hundred and fourteen units showed neither liquid tracer nor microbial
      ingress. One hundred and eight units were positive for both microbial and liquid
      tracer ingress. No test units were positive for microbial ingress but not for
      liquid tracer ingress. Fifty-eight units were positive for liquid tracer ingress
      but failed to show microbial ingress. Logistical regression was used to
      demonstrate that the probability of liquid tracer ingress was greater than
      microbial ingress at all leak sizes. The results indicate that the liquid tracer
      method studied herein was a useful indicator of the microbial barrier properties
      of pharmaceutical packaging. Additionally, the results support the contention
      that liquid penetration of a leak is required for microbial ingress.

PMID- 10969528
TI  - Validation of critical process input parameters in the production of protein
      pharmaceutical products: a strategy for validating new processes or revalidating
      existing processes.

PMID- 10969529
TI  - Enumeration of total viable microorganisms in an antibiotic raw material using
      ChemScan solid phase cytometer.
AB  - A preliminary study was performed for the enumeration of microorganism
      contamination of the macrolide antibiotic, Spiramycin, using epifluorescence with
      the ChemScan solid phase cytometer. The artificial spiking of Spiramycin powder
      antibiotic with pure culture of four microorganisms led to complete recovery of
      the tested organisms, whatever their sensitivity to the bacteriostatic activity
      of the drug. With the conventional plate method run in parallel, complete
      recovery was only obtained for Spiramycin resistant organisms. The spiked
      microorganisms that were sensitive to the antibiotic remained inhibited or
      stressed by the action of the Spiramycin and did not grow on the plate.

PMID- 10969530
TI  - On the cause of performance variation of biological indicator used for sterility
      assurance.
AB  - Variations in biological indicator (BI) lethality have been reported for several
      types of commercial BIs. This phenomenon has been observed among different lots
      of the same species and strain BIs from a single vendor. It has also been
      reported among BIs from different vendors but of the same species and strain that
      are intended to challenge the same general type of sterilization process.
      Although BI variability has been widely reported, the contributing factors to the
      variation in observed lethality have not been specifically identified. This is
      because the previous reports overlooked, to some extent, the differences in
      carrier materials, primary packaging materials, and culture media used in the
      manufacture of commercial BIs. The differences in lethality attributable to the
      carrier material, for so called "substrate effects," have been widely reported.
      For the BI preparation in this experiment, the same carrier material, primary
      packaging material, and culture medium were used. The only variable was the use
      of different spore suspensions supplied from different BI manufacturers. The
      authors found no significant difference in BI performance as measured by BI
      resistance. BI population may vary depending on the retrieval technique or
      population variability in a purchased BI suspension. Unlike some previously
      published studies, there was no indication from our studies that a specific BI
      manufacturer supplied BIs with either greater resistance or greater population.

PMID- 10969531
TI  - Particulate matter determination in LVPs produced in Dutch hospital pharmacies.
      Part 2: Overview of the results.
AB  - The Laboratory of Dutch Pharmacists determines LVP particulate matter
      contamination of LVPs produced in Dutch hospital pharmacies. The investigated
      LVPs must conform to the NVZA/LNA criteria, which prescribes eight samples and
      sets limits for particles > or = 2 microns, > or = 5 microns, > or = 10 microns,
      and > or = 25 microns for both mean and mean + 2x standard deviation. LVPs
      produced in 500 mL glass containers or plastic containers mostly met the NVZA/LNA
      criteria, but LVPs produced in 100 mL glass containers showed higher levels of
      particulate matter contamination. The composition of the LVP significantly
      affected the extent of particulate matter contamination, but the effect was
      relatively small when compared to the influence of the type of container. LVPs
      produced in Dutch hospital pharmacies and LVPs obtained from pharmaceutical
      industries showed comparable amounts of particulate matter contamination.

PMID- 10969532
TI  - Dealing with the nanobacteria, if we must.

PMID- 10969533
TI  - [Laboratories, distilleries, balm makers. The oil activity in Thuringen forest
      from the 17th to the 19th century].

PMID- 10969534
TI  - [The nomenclature of cosmetic contents. Can the pharmacist unterstand it? An
      overview of the synthesis of excipients and their possible adverse effects].

PMID- 10969535
TI  - [Structure, function and potential therapeutic possibilities of NMDA receptors.
      2. Therapy concepts and new receptor ligands].

PMID- 10969536
TI  - [Drug quality control--the contribution of pharmacy to drug safety. The
      historical development of the Working Group for Drug Control-Pharmaceutical
      Analysis of the German Pharmaceutical Society. 2].

PMID- 10969537
TI  - [Injuries of the inferior tibiofibular syndesmosis].

PMID- 10969538
TI  - [Injuries of the inferior tibiofibular syndesmosis].
AB  - The incidence of isolated distal tibiofibular syndesmotic ruptures in acute ankle
      sprains lies between 1% and 11%. These injuries are frequently overseen or
      misdiagnosed as anterolateral rotational instability of the ankle and often
      become apparent through protracted courses. Although the pathomechanics and
      extent of syndesmotic injuries have been systematically described by Lauge-Hansen
      and Weber, no generally accepted guidelines exist as to when these complex
      injuries are to be treated surgically to ensure sufficient and stable healing of
      the syndesmosis besides correct alignment of the distal fibula. So far,
      systematic follow-up regarding syndesmotic injuries in ankle fractures is
      missing, although it has long been recognized that tibiofibular diastasis
      secondary to chronic syndesmotic instability leads to external rotation of the
      talus. In combination with a valgus position of the talus, this instability leads
      to a decrease in the contact area which results in posttraumatic arthritic
      changes. This paper reviews the standard diagnostic and therapeutic procedures
      for acute syndesmotic ruptures in fracture dislocations of the ankle. Among the
      few corrective procedures advocated for chronic syndesmotic insufficiency are
      tibiofibular arthrodesis, synthetic ligament substitutes, and tenodesis with the
      peroneus brevis tendon. A sufficient reconstruction must restore the stability of
      the ankle mortise and alignment of the fibula in the tibiofibular incisura to
      ensure limitation of talar rotation. Therefore, a tenodesis was developed which
      substitutes the three important ligaments of the syndesmotic complex. The Casting
      procedure for chronic syndesmotic insufficiency was modified with reconstruction
      of the interosseous tibiofibular ligament in addition to the anterior and
      posterior tibiofibular ligaments. The resulting three-point fixation of the
      distal fibula appears more anatomically, physiologically, and biomechanically
      advantageous. The operative procedure is given in detail. Distal tibiofibular
      syndesmosis. Persistent instability of the distal syndesmosis. Ankle fractures.
      Syndesmotic screw.

PMID- 10969539
TI  - [Acute pseudo-obstruction of the colon as complication of hip surgery].
AB  - Pseudo-obstruction of the colon is characterized by a massive colonic dilatation
      without mechanical obstruction. It is rarely after hip surgery, however,
      untreated it may be complicated by a life threatening perforation of the colon.
      In a retrospective analysis we reviewed 11 patients (4 women, 7 men, mean age
      75.2 years, range 67 to 86 years) with pseudo-obstruction of the colon after hip
      surgery in the years 1995 to 1998. In relation to all patients aged 65 years and
      older who underwent surgery of the hip, the prevalence was 1.06%. The leading
      clinical symptom was abdominal distension. On plain x-rays, dilatation of the
      colon measured 13.3 cm on average (9-16 cm). In two patients (18%) adequate
      application of drugs stimulating the gastro-intestinal motility was sufficient,
      whereas in 8 patients (73%) colonoscopic decompression had to be performed. In
      three of these, the procedure failed and because of persistent symptoms a
      cecostomy was performed. One patient underwent immediate laparotomy because of
      peritonitis. 2 patients (18%) died because of a complicated course. Non operative
      treatment should not exceed 24 hours, endoscopic decompression and tube placement
      is considered as the treatment of choice. In cases of failure of these
      procedures, perforation of the colon and/or peritonism, urgent laparotomy with
      open decompression by a cecostomy is essential.

PMID- 10969540
TI  - [Outcome of surgically treated lateral clavicle fractures].
AB  - This retrospective study presents the results of 41 patients with a lateral
      clavicle fracture eight years after the treatment at the Staatliche Orthopadische
      Klinik of the LMU Munchen in the time between 31.10.1979 and 31.10.1994. It could
      be shown that the lateral clavicle fractures, due to their variety, hold a
      special position among the clavicle fractures and thus need a differentiated
      therapeutic procedure. Among the operation methods the K-wire stabilisation with
      cerclage was the most often chosen operation technique i.e. in 24 cases. The K
      wire without cerclage was used in two cases. Twelve fractures were treated with
      AO-plate-osteosynthesis. Three fractures had to be treated by resection, as they
      produced two pseudarthrosis and one serious AC-arthrosis during the conservative
      therapy. 92.7% of the subjective results of the 41 checked up patients were good
      and very good. The clinical follow-up of 36 and the radiological follow-up of 33
      patients revealed in 97% a good and very good outcome in the Boenisch-Score.

PMID- 10969541
TI  - [Ligament repair and/or capsulodesis in scapholunate instability].
AB  - We have reviewed 37 patients with scapholunate instability, operated in Paris
      between 1979 and 1995 7 months after the injury. There were 12 partial and 18
      complete ligament ruptures, but also 4 distensions. The repair was a secondary
      suture in 16 cases (7 direct, 1 transosseous, 1 combined, 5 anchor, 2
      transosseous with anchor). A capsulodesis was performed 7 times as an isolated
      and 8 times as a combined procedure. 6 previous cases have been treated by
      ligamentoplasty. We present the results after a mean postoperative follow-up of
      27 months, with good results on pain and grip, maintaining a satisfactory range
      of motion.

PMID- 10969542
TI  - [Injuries of parasagittal bridging veins in fatally wounded victims of motor
      vehicle accidents].
AB  - Experimental data and clinical as well as postmortem experiences have indicated
      that subdural hematomas are less frequent in acceleration injuries in traffic
      accidents compared to falls or assaults. The present report demonstrates that
      this does not hold true in the same way for bridging vein ruptures (one of the
      predominant causes for subdural bleedings). Ruptures of these vessels without
      subdural bleeding (SDB) are only seldom mentioned in the literature. However, if
      no SDB is present, no one will look for these structures. In our institute a
      systematic analysis of the bridging veins in all cases of lethal blunt head
      injury is made: prior to the careful morphological preparation we investigate
      these vessels by radiographic imaging after filling with contrast medium. 6 car
      passengers (age between 4 and 31 years) which suffered a lethal head injury were
      examined in the last year. 2 victims had impressed fractures with cerebral
      compression injuries. In 1 case the base of the skull was broken and in 3 cases
      no skull fracture was present; no serious focal brain injury had occurred in
      these 4 cases, but 3 victims had signs of diffuse brain injury. In 5 cases a
      direct impact of the head against the interior of the car was obvious. In 5 cases
      ruptures of several bridging veins could be demonstrated. In one case (survival
      for 3 days) a minor SDB (20 ml) was present and the ruptures had been closed by
      thrombosis; another victim died at the scene. The other 3 victims survived
      between 4 and 15 hours without developing SDB and without closing of the ruptures
      by thrombosis. This combination is surprising and shows that our knowledge
      concerning the relationship between bridging vein ruptures and SDB is restricted.
      The frequency of bridging vein lesions in severe head injuries is likely
      underestimated in the clinical as well as in the postmortem literature. A rapid
      increase of intracranial pressure after the accident resulting in a collapse of
      the cerebral circulation is probably responsible for the absence of the SDB in
      the presented cases.

PMID- 10969543
TI  - [Molecular and phenotypic characterization of methicillin-resistant
      Staphylococcus aureus isolates. Studies at a traumatic surgery clinic, 1994
      1997].
AB  - Methicillin resistant Staphylococcus aureus-strains, isolated from 1994 to 1997
      from patients of the traumatic surgery hospital Tubingen, were compared using
      lysotyping and pulsed-field gel electrophoresis. Both typing methods detected two
      clones causing an outbreak 1994 in 6 patients and a third endemic clone of MRSA,
      which was isolated from 5 patients (1995), 4 patients (1996), and 6 patients
      (1997). Additionally other MRSA-types were found in 6 cases of which
      transmissions occurred in up to three patients. An epidemiological connection to
      MRSA isolated from patients of the university hospital of Tubingen was made.
      Possible consequences for patient management and antibiotic strategies in MRSA
      infections were discussed.

PMID- 10969544
TI  - [Surgical treatment possibilities of advanced carpal collapse (SNAC/SLAC wrist)].
AB  - Longstanding and untreated scaphoid fractures and scapholunate dissociations lead
      to painful destruction of the wrist with carpal collapse. The severity of
      degenerative arthrosis is classified in three stages and can be treated adequate
      operatively. SNAC wrist (scaphoid nonunion advanced collapse) after failed fusion
      of the scaphoid and SLAC wrist (scapholunate advanced collapse) after
      scapholunate dissociation should be differentiated. The reconstruction of the
      scaphoid or scapholunate ligament in stage II and III is no reasonable option.
      Motion preserving procedures such as proximal row carpectomy or midcarpal
      arthrodesis are preferable in this situation. Thirty-one male patients (average
      41 years) were treated for SNAC or SLAC wrist with midcarpal arthrodesis. All
      patients were reexamined, the mean follow-up was 15 months. Grip strength was
      measured with the Dexter-System, pain was evaluated by a visual analogue scale
      (VAS 0-100). Patients' daily activities and general quality of life were
      estimated with the DASH-questionnaire. Pain was reduced to 50% compared to the
      preoperative situation. Grip strength improved to 60% of the opposite side.
      Active range of motion reached 50% of the contralateral wrist. Total DASH-score
      reached 39.0. Nonunion at the fusion site necessitated additional surgery in four
      patients resulting in total wrist arthrodesis. 80% of the patients returned to
      their original occupation. Midcarpal fusion is a reliable procedure for treating
      the difficult condition of advanced carpal collapse if proper realignment of the
      carpus is performed. The DASH-score reflects the subjective impressions of the
      patients in daily life and justifies the choice of a salvage procedure preserving
      wrist mobility. Total wrist fusion represents the last line of defense.

PMID- 10969546
TI  - [Finger and middle hand fractures. Surgical and nonsurgical treatment procedures.
      II].

PMID- 10969545
TI  - [Associated injuries in severe pelvic trauma].
AB  - There has been a marked increase in the incidence of pelvic fractures over the
      last few years. Associated injuries to the urogenital and vascular system as well
      as nerve injuries worsen the prognosis. Over a five year period 126 patients with
      severe pelvic trauma were treated. Out of these 39 (30.9%) sustained additional
      peripelvic injuries and represent the study sample. Type B injuries according to
      the AO classification occurred in 16 (41%) patients, type C fractures in 23 (59%)
      patients. The spleen, liver and kidney were the most frequently injured organs
      (58.9%), followed by urogenital lesions (46.6%), nerve injuries (25.6%) and
      vascular lesions (15.3%). The most common extrapelvic lesions were thoracic
      injuries in 56.4% and severe head injuries (GCS < 8) in 33.3%. The mean Hannover
      Polytrauma score was 35.6 points, the mean Injury Severity Score 27.6 points.
      Osteosynthesis was performed in 21 pelvic ring fractures (53%), eight procedures
      (50%) in type B fractures and 13 (56%) in type C fractures. In type B injuries
      the anterior pelvic ring was stabilized with a tension band wiring in four cases,
      in two patients with an external fixator and with plate osteosynthesis in one
      case. In type C injuries the external fixator was applied as the only stabilizing
      procedure in six patients. In four cases the anterior ring was fixed with tension
      band wiring or plates and the dorsal aspect of the pelvic ring with sacral bars.
      Three patients had their additional acetabular fracture plated through a anterior
      approach. All surviving 28 patients were followed up for an average of 18 months
      (range 7-59 months) after the trauma. The patients were classified using the
      pelvic outcome score proposed by the German Society of Trauma Surgery. 53.4% of
      the type B fractures showed a good clinical outcome, 47.6% a poor outcome. 15.4%
      with type C fractures presented with a good outcome, 84.6% with a poor outcome.
      80% of the type B and 23% of the type C fractures had a good radiological
      outcome. 20% of type B and 77% of type C injuries had a poor radiological
      outcome. Five patients (12.8%) sustained persistent urological symptoms. Three of
      these had urinary dysfunction, two used permanent cystotomies due to their severe
      neurological deficit after a head injury. Ten patients with nerve injuries at the
      time of trauma suffered long term neurological dysfunction of the lumbosacral
      plexus. The mortality rate was 28%. Seven patients died in the emergency room due
      to uncontrollable bleeding, four in the intensive care unit from multi-organ
      failure. The management of complex pelvic trauma consists of fracture treatment
      and interdisciplinary treatment of the associated injury. Lesions of the
      abdominal organs or of major vessels must be addressed first if hemodynamic
      instability is present. Injuries to smaller vessels can be embolized
      percutaneously. Urinary bladder ruptures are treated as an emergency, urethral
      lesions electively after four to six weeks. We recommend external fixation of the
      pelvis in the acute phase for control of both the osseous instability and control
      of haemorrhage through external compression. The treatment of choice for the
      anterior pelvic ring is tension band wiring or plating. If this is
      contraindicated due to an open fracture external fixation is the treatment of
      choice. Type C fractures require posterior ring stabilization which should be
      postponed until four days post admission.

PMID- 10969547
TI  - [Spontaneous fracture of the tibia after replacement of the anterior cruciate
      ligament with absorbable interference screws. A case report and review of the
      literature].
AB  - We report a granulomatous inflammatory reaction after administration of
      absorbable interference-fit screws for fixation of patellar-tendon-autograft in
      anterior-cruciate-ligament reconstruction, leading to spontaneous fracture of the
      tibia. Radiological evaluation demonstrated osteolytic lesions at the
      interference-fit screw insertion-site. Histological findings included a sterile
      inflammatory reaction and giant-cell formation.

PMID- 10969548
TI  - [Secondary hypertrophic osteoarthropathy. Differential diagnosis of post
      traumatic ossification of the interosseous crural membrane].
AB  - The case of a 48-year-old patient is presented, suffering from persisting pain in
      the right lower leg for more than a year following a distortion of the ankle. The
      patient was known to have a history of severe asthmatic disease. Conventional X
      rays showed a periostitis of the lower tibia and fibula. To exclude a malignant
      process, an open biopsy was performed. Neither tumor nor any histological signs
      of chronic inflammation were found. The patient claimed to have a similar pain in
      the contralateral lower leg 5 months after initial biopsy. X-rays again showed
      signs of a periostitis of the tibia and fibula. Furthermore, an increase in
      isotopes in this area was found in a performed bone scan. Diagnosis of
      osteoarthropathia hypertrophicans was confirmed 2 years after onset of the first
      symptoms. Pathogenetic variables both of the primary and secondary forms of
      hypertrophic osteoarthropathy (HOA) are as yet not completely clarified.
      Secondary hypertrophic osteoarthropathy (SHOA) may be defined as a syndrome of
      the long bones with clubbing of the fingers and toes, and occurs in the process
      of chronic lung and mediastinal disease. We conclude that HAO detection may
      contribute to early detection of lung disease, especially bronchopulmonary
      cancer, before it becomes clinically and radiographically manifest.

PMID- 10969549
TI  - [Resection of the calcaneus as a treatment option in osteitis following an open
      calcaneus fracture].
AB  - Surgical treatment of calcaneal fractures is demanding due to the poor
      musculocutaneous coverage. Infection with osteitis is a severe complication with
      open fractures. The appearance of osteitis requires aggressive surgical treatment
      including amputation in case of persistence, leading to considerable invalidism.
      We report the case of an 37-year-old mason with an grade III open calcaneal
      fracture caused by a fall. Osteitis appeared after primary osteosynthesis with
      open reduction and eventually--after several revisions--required a calcanectomy.
      By preservation of the forefoot and midfoot and thanks to sufficient orthosis
      treatment the patient was able to return to his profession after eight months.

PMID- 10969550
TI  - [A surgeon in the morning].

PMID- 10969551
TI  - [Necessary indication of life-threatening sepsis. Relationship of the surgeon
      with treatment refusing patient].

PMID- 10969552
TI  - [Indicators of continuous improvement of the transfer of neonatal emergency cases
      in the Trento province].
AB  - The nursing personnel of the Neonatology Unit of Trento Hospital cares for the
      transportation of newborns in the Trento Province (more than 7500 transportations
      have been performed to date). Aim of the study is the evaluation of the quality
      of care as documented in the ad hoc neonatal transportation data-bank. A further
      goal is the formulation and validation of simple and easy to collect indicators
      of "improvement of care". Examples of indicators used to assess the activities of
      the years 1996 and 1997 were the number of transportations with functioning
      equipment; the number of newborns with body temperature registered; the number of
      transportation cards correctly filled out. These simple indicators allowed to
      identify areas where the quality of care could be improved. The cause-effect
      diagram used allowed the involvement of all the nursing personnel in the
      identification of problems and of possible solutions. An example of the process
      followed for identifying and preventing hypothermia is presented and discussed.

PMID- 10969553
TI  - [Medicated intravascular catheters. Review of the literature].
AB  - Central Venous Catheters (CVC) are widely used in the setting of intensive care
      units, but they are associated with an increased risk of CVC-related infections.
      To prevent infections originated from CVC, a number of devices have been more
      recently produced, that are characterized by the presence of
      antiseptic/antibiotic substances in the matrix of the CVC itself ("impregnated"
      CVC). In this brief review, more recent studies on the topic are discussed,
      especially in the light of guidelines from the CDC. Although from these studies
      many suggestions about the efficacy of impregnated CVC in the prevention of CVC
      related infections can be derived, notwithstanding the critical role of
      preventive measures during CVC procedures must be recognized as the principal
      factor in reducing CVC infections.

PMID- 10969554
TI  - [Decubitus lesions in patients referred to acute and post-acute home nursing care
      for the elderly in Genova].
AB  - The Elderly Services of USL 3 "Genovese" together with the team for Continuing
      Education designed and implemented a survey on the elderly clients referred to
      the home care and nursing home services. The aim of the study was to describe the
      frequency, distribution and severity of pressure ulcers. The data were collected
      during a period of seven months: from 1st November 1997 to 31st May 1998. One
      thousand seven hundred and twenty nine clients were observed; 705 (41%) had
      single or multiple pressure ulcers. Patients with multiple pressure ulcers
      accounted for 42% of the total. The sacrum was the most affected site (43% of the
      patients with a single ulcer and 33% with multiple ulcers). Patients with severe
      pressure ulcers (stages 3 degrees and 4 degrees NPUAP classification) accounted
      for 42% of the total. Pressure sores were observed in 15% of "at no risk"
      patients and in 40% of those at low risk (Norton Scale score). The study
      highlighted a lack of documentation (90% patients) on treatments performed in the
      hospital and prescribed at discharge for the pressure sores. These findings
      reflects possibly the fact that this aspect of care is unduly disregarded by
      nursing personnel, and that a goal-oriented retraining, underlining also the need
      of appropriate documentation, is warranted.

PMID- 10969555
TI  - [Transfer to nursing care of patients with problems occurred during hospital
      care].
AB  - The innovative experience of the participation of a Registered Nurse in the
      Hospital Therapeutic Committee is described. The occasion for the participation
      was the drawing up of the Hospital Therapeutic Reference Book. The nurse had an
      active role in the identification of problems related to the practical use of
      drugs. Problems emerged, concerning the choices of the Committee and the
      implications for nursing care are discussed. The nurse can have a positive impact
      and her/his presence in the Therapeutic Committees should be mandatory.

PMID- 10969556
TI  - [In-hospital nursing triage: a new professional trend in the organization of an
      up-to-date emergency department].

PMID- 10969557
TI  - [The needs of relatives of patients admitted to intensive care units in the
      Trentino region].
AB  - The perception of needs of relatives of patients admitted to the Coronary Care
      Units (CCUs) and Intensive Care Units (ICUs) of the Trentino region was
      investigated by interviewing 50 relatives and 72 nurses. The questionnaire used
      for the survey included a list of 31 potential needs of a relative. Relatives and
      nurses were asked to select 10 needs and rank them according to the perceived
      priority; the nurses were also requested to rate the level of satisfaction
      related to each need, on a scale from 1 to 4. The data were collected over a
      period of 50 days, from the end of May to the beginning of July. The priority
      ranking of needs by relatives was as follows: being sure that the patient
      receives the best possible care; that the relative could see a doctor at least
      once a day; and being contacted and informed on every clinically relevant change
      in the health-illness status of the hospitalised relative. There was a good
      correspondence between relatives and nurses' perceptions while no significant
      differences in the perception of needs was observed between relatives interviewed
      in CCUs and ICUs, neither between nurses with different levels of expertise.
      Nurses perceive that the priority needs identified by the relatives are
      reasonably satisfied.

PMID- 10969559
TI  - [Written information: evaluation of an informative leaflet for patients
      undergoing colonoscopy].
AB  - Client teaching and information on medical procedures and care organisation is
      recognised as one of the most important tasks for the nurse. The information must
      be complete, detailed, and personalized according to the client culture and
      learning capacity. To address these points, an information booklet has been
      designed to inform clients undergoing colonoscopy in the gastroenterology unit of
      Azienda Ospedaliera Careggi, Florence. The booklet, together with a multiple
      choice questionnaire aimed at evaluating clients' satisfaction with the
      information provided, was distributed to 100 clients undergoing a colonoscopy
      over a two-month period in 1998. The results of the survey suggest that the
      booklet has been instrumental in client learning about the procedure, as shown by
      the high positive satisfaction response provided to the questionnaire. Moreover,
      contents provided are clear and easy to understand. Clients would like to have
      specifically detailed information on the way the exam is performed, on its
      duration (22%) and on the disinfection procedures (21%). At present, all the
      patients booked for colonoscopy receive the booklet in their homes.

PMID- 10969558
TI  - [Analysis of the educational needs of nurses of the emergency services in the
      Veneto Region].
AB  - The perceived level of competence of nurses working in the emergency services of
      the regione Veneto was evaluated with a questionnaire, distributed to the 906
      nurses working in First aid and Emergency Departments. 490 questionnaires were
      returned (54%). The aim of the survey was to identify the educational needs of
      the nurses. The panel of experts that devised the questionnaire identified the
      main skills required by emergency nurses and set the standard level of
      performance to be achieved: 4.5 on a scale from 0 to 5. The mean level of
      performance for skills such as the identification of vital signs, ambu
      ventilation, cardiac massage, and oxygen delivery is never lower than 4. The
      areas of management of patients with cardiac arrhythmias, drowning syndrome,
      metabolic disorders, require specific reinforcement with ad hoc courses. The
      pattern of perceived competence is similar for the nurses that work in
      ambulances, in Emergency services and in First Aid Departments. While a better
      level of performance has been found in nurses working in emergency services.

PMID- 10969560
TI  - [Nursing interventions for patients with chronic heart failure].

PMID- 10969561
TI  - [Cardiovascular drugs and therapy].

PMID- 10969562
TI  - [The AIDS emergency].

PMID- 10969563
TI  - [Patients with Down syndrome do not need tears].

PMID- 10969565
TI  - [Respect for wonders and mysteries of life: Jean Watson's theory on patient
      care].

PMID- 10969564
TI  - [Web-publishing on the Internet].

PMID- 10969566
TI  - [Advanced educational course in the management of cancer: besides professional
      knowledge and skills, empathy is also needed].

PMID- 10969567
TI  - [Care of female cancer patients: treatment models to be used creatively and
      individually].

PMID- 10969568
TI  - [Advances in rehabilitation through basal stimulation].

PMID- 10969569
TI  - [Holotropic respiration therapy: new ways in psychologic pain therapy].

PMID- 10969570
TI  - [Patient's instruction: I do not want a physician--I want to die].

PMID- 10969571
TI  - [Existential experience in the diagnosis of cancer: encouraging self-help].

PMID- 10969573
TI  - [Public relations--a factor in nursing service: yes or no?].

PMID- 10969572
TI  - [Key qualifications in nursing care: new requirements to master new
      qualifications].

PMID- 10969575
TI  - [Impractical theoretic treatises do not serve nursing care].

PMID- 10969574
TI  - [Everyday medicine and nursing on TV: patient care in hospital series].

PMID- 10969576
TI  - [Excessive help--can become dangerous].

PMID- 10969577
TI  - [Initiative for burns victims is introduced by the state: "we went through fire
      and survived..."].

PMID- 10969578
TI  - [Clinical nursing research. New standards for quality assurance for nursing and
      patient].
AB  - Nursing as a health-service has a long tradition, nursing research however, a
      relatively short history. Florence Nightingale was the first to publish about
      nursing research in the year 1858. Since Nightingale, the need to study and
      improve the efficacy and efficiency of nursing has steadily increased. More than
      ever before, society needs nursing based on scientific knowledge and not just on
      unchallenged rituals and traditions. This scientific knowledge base can be
      acquired by clinical research. Within multidisciplinary clinical research it is
      necessary to focus on nursing's unique function. Virginia Henderson (1955) and
      Dorothea Orem (1959) have clearly explicated this function. Designs for clinical
      nursing research can be (quasi-) experimental, correlational or descriptive.
      Descriptive research can be qualitative or quantitative. Effects of nursing
      interventions on decrease of self-care problems and improvement of self-care
      capability and behaviors, should be investigated by experimental or quasi
      experimental studies. Some examples of clinical nursing research are given. The
      first example demonstrates the effect of quantity and quality of nursing staff on
      patient's capabilities for hygiene self-care. The second example explicates the
      relation between self-care and quality of life with breast-cancer patients under
      chemotherapy treatment. The last example shows the effect of diabetes education
      on self-care behaviour and metabolic control. The examples given demonstrate the
      importance of clinical research focused on nursing's unique function. In order to
      accomplish this, programs of research are needed as well as close co-operation
      with nursing services, physicians and hospitals. Only when research findings are
      discussed and implemented in multidisciplinary teams, nursing will become more
      evidence-based.

PMID- 10969579
TI  - [Central and decentralized aspects of the development and implementation of a
      concept of quality].
AB  - This article presents component parts of quality concepts of the nursing
      administration in the Swiss Paraplegic Centre Nottwil. These concepts are based
      on centralised and decentralised methods of quality assurance and improvement.
      Both methods were modified so as to compensate for their disadvantages. Thereby
      the demand for systematic scientific control, which is set out in the Swiss
      health insurance laws, can be achieved. For this purpose a general framework of
      quality requirements specific to the institution for rehabilitative nursing was
      developed along with nursing quality standards for specific topics. By both
      methods, the emphasis is on the inclusion of staff in the development as well as
      in scrutiny of quality criteria/requirements. In this way a high level of
      acceptance of quality criteria will be reached among the staff. The quality
      concept presented here reflects the vision that quality should not be seen as a
      heavy burden but as an every-day necessity.

PMID- 10969580
TI  - [Focus group interviews: a qualitative research approach to nursing].
AB  - Focus Group interviews have become a popular technique for nursing research. This
      article introduces basic guidelines for the application of the methodology
      through a literature review and an example from nursing research. General and
      specific study design issues are covered.

PMID- 10969581
TI  - [Water births and the exposure to HIV].
AB  - The risk of a work related HIV-exposure or infection to midwives, or other HCW,
      in attending waterbirths of (possible unrecognized) HIV-positive women is
      unknown. Our goal was the quantification of the loss of blood of the childbearing
      woman after a waterbirth into the waterpool, in taking pool-water-samples of 14
      different waterbirths and measuring the hemoglobin in the plasma, and then
      correlating the mean found loss of blood and the mean quantity of poolwater with
      a hypothetical HIV-RNA viral load of 10(3)-10(6) copies per milliliters (ml)
      blood. All attended waterbirths were evaluated with a questionnaire regarding:
      parity of the child-bearing woman; serostatus for HIV/Hepatitis-B (HBV) and
      Hepatitis-C (HCV); length of the birth-process; perineum-rupture or not, etc.
      Questions concerning the HCW in implementing universal precautions like: type of
      gloves and garment used, if at all; duration of water contact with the hands;
      existing skin lesions; HBV-vaccination-status; years of professional experiences
      as a midwife; how many waterbirths attended etc. were also evaluated. The mean
      calculated loss of blood into the pool was 300 ml, the mean pool-water content
      633 liters. With a hypothetical (maximal) HIV-RNA viral load of 10(6) copies per
      ml blood, we calculated a mean HIV-RNA viral load of 476 copies per ml pool
      water. We also found 37% of the interviewed midwives (n = 14) to have skin
      lesions on hands or fingers; 1 received splashes into her (unprotected) face and
      1 was not immunized against HBV. The mean loss of blood of 300 ml into the pool
      is a relevant amount. The skin-contact of the HCW with the potentially
      contaminated water is the norm, because of the failure of the type of used
      gloves. Because of the diluting effect of the poolwater, we estimate the
      potential risk for a HIV-exposure to intact skin as minimal and, therefore a
      potential HIV-infection as "low level" and to be unlikely. However, a risk for
      nosocomial HBV-infection is significantly higher. We recommend wearing long
      sleeved gloves, waterproofed garment, and HBV-vaccination to all HCW.

PMID- 10969582
TI  - [Project for supporting visually handicapped aged persons: developing a guide for
      the community of Munster].
AB  - In this paper we wish to outline both the function and the role of projects as
      part of a course in "Nursing Education" (Pflegepadagogik) at the Fachhochschule
      Munster, as well as to present a specific project which has enabled the students
      to gain experience in project management and qualitative research. The project
      target group were visually handicapped old people for whom a guide was produced
      as a health promotion strategy within the framework of governmental health
      objectives in the state of Northrhine-Westfalia.

PMID- 10969583
TI  - [Prevention of falls in acute hospital care. Review of the literature].
AB  - Patient falls frequently occur in institutions of health care. Various
      occurrencies may cause patient falls; and sometimes have grave consequences for
      the people involved, affecting their quality of life. Falls often result in
      longer stays in hospital and/or in rehabilitation institutions. Hence patient
      security and prevention of falls become a quality factor for the health care
      professionals. The literature search on the subject of fall prevention in acute
      care from a nursing perspective encompasses the years 1988-1998 (MEDLINE,
      EMBASE). 21 articles were thoroughly examined. The prevention strategies are
      essentially based on risk assessment (guess of fall danger), intervention
      (preventive care measures) systematic reporting of the incidents of falls and
      their consequences. Introduction of the preventing programs and measures resulted
      in a considerable reduction of patient falls. The preventive measures focussed on
      reducing the risks of falling in everyday clinical life by increasing attention
      and presence of the staff caring for patients. The methods used were descriptive
      or exploratory. Despite plausible reports, connections between preventive
      measures and a reduced number of patient falls were not scientifically proven.
      Further investigations to the effectiveness of caring measures concerning fall
      prevention in acute care of experimental or quasi-experimental design are needed.

PMID- 10969585
TI  - [The situation of foreign-born dementia patients and their families in the
      Federal Republic of Germany].
AB  - The care given to dementia sufferers by family and professional carers will
      become a central topic of social policy given the drastic increase of the elderly
      population in the near future. Since the population of elderly migrants is
      growing even faster, the care situation of migrants with dementia will gain all
      the more in importance. Consequently, after giving some background information on
      elderly migrants and on the care of dementia sufferers in Germany, this article
      focuses on the interviews of family caregivers as well as selected experts
      regarding the present care situation of migrants with dementia. The interviews
      show for example that, on the side of the migrant patients and caregivers, the
      low level of education, poor skills in the host language as well as strong roots
      in a traditional and religious way of thinking seem to hinder a better care as
      much as, on the other side, the insufficient adaptation of the care given by the
      existing counselling and care structures to specifically meet the needs of
      elderly migrants.

PMID- 10969584
TI  - [Stroke is a catastrophe for the patient--how does nursing care meet the needs of
      younger patients?].
AB  - A stroke is a crisis. However, psychosocial, emotional and spiritual aspects of
      this illness are not described in nursing literature. Nursing interventions focus
      on the rehabilitation of physical impairment and speech problems. This article
      examines emotional aspects of a stroke. A comparison of these aspects as
      described in nursing literature and from psychological literature about crisis
      and coping illustrates the emotional side of a stroke. Through this comparison it
      becomes evident that a lack of knowledge, particularly in nursing in Germany,
      exists. Further, the situation of the 25% of people who have a stroke and who are
      still in the working process, is not described in the nursing literature. In
      order to be able to provide physical and emotional care for these people we need
      not only adequate conditions but also scientifically proved knowledge and
      concepts that fit practice needs.

PMID- 10969587
TI  - [Prospects for national health expenditure in Japan].
AB  - Japan's national health expenditure has been increasing by 5% annually
      (approximately 1.3 trillion yen) and is expected to reach 30 trillion yen in the
      1999 fiscal year. This increase is mostly due to the country's rapid aging rate.
      However, Japan's current slow economic growth, combined with a decrease in the
      average number of children per family, raises the issue of how these health
      expenditure increases can be afforded as the health care system continues to
      provide appropriate levels of essential health care services. To understand these
      health-expenditure trends, one must first recognize that the Japanese health care
      system is characterized by the country's social health insurance system, which is
      based on the Social Insurance Act. It is also important to consider the impact
      the medical fee schedule has on clinical practices. This article reviews the
      situation surrounding national health-care expenditures and the related issue of
      social health-insurance reform. In this, several topics closely connected with
      cancer therapies are also examined.

PMID- 10969586
TI  - [Isolated tumor cells and micrometastasis--clinical behavior and therapeutic
      implications].
AB  - Recent advances in the detection of both isolated tumor cells and micrometastases
      in distant organs by means of immunocytochemical and molecular biological
      techniques have brought a new paradigm for the understanding of cancer biology.
      For instance, although the presence of a micrometastasis is a significant
      indicator of poor prognosis, it is now widely accepted that certain residual
      tumor cells remain dormant for a long period without any treatment. Many
      investigators have focused on what is different in the nature of the dormant and
      active tumor cells, and how microtumors can acquire the active phenotype in
      ectopic distant organs. In addition, information on both isolated tumor cells and
      micrometastases is useful not only for staging but also for considering an
      adjuvant treatment schedule. This review summarizes the recent clinical outcomes
      of the investigations of both isolated tumor cells and micrometastases.

PMID- 10969588
TI  - [Cost-effectiveness of cancer therapy].
AB  - Under recent healthcare reforms, the urgent need for establishing evidence-based
      healthcare and for economic evaluation has been emphasized. Cancer not only
      accounts for a major burden of diseases, but also has major economic impacts on
      both individual patients and society. Most cancer therapies are essentially high
      cost and high-technology, and provide uncertain outcomes. Concerns about the
      appropriate choice and utilization of cancer therapy is increasing. However,
      economic evaluations for cancer therapy are lacking in a number of areas, despite
      recent advances. In Japan, to catch up with international trends, serious efforts
      to generate better evidence for economic evaluation of cancer therapy have
      recently been made. A league table for economic evaluation of cancer therapy in
      Japan has been constructed, based on results including preventive antiemetic
      treatment, breast conserving and post-adjuvant therapy for early breast cancer,
      bone marrow transplantation for leukemia, interferon treatment for hepatitis C
      with liver cirrhosis, and others. This information shows substantial
      possibilities for evaluating the value-for-money of cancer therapy. This may lead
      to the establishment of an effective and efficient healthcare system in Japan.

PMID- 10969589
TI  - [Problems concerning the prices of surgical operations in Japan. Union of Social
      Medical Insurance Committee Members of Surgical Societies in Japan].
AB  - The Union of Social Medical Insurance Committee Members of Surgical Societies in
      Japan was established in 1967. The union has tried to develop scientific methods
      to assess the price of surgical operations in Japan and proposed a tentative plan
      for the assessment of the price of operations. The price of an operation includes
      personnel expenses and other costs such as the prime costs to repay loans for
      land and buildings, and taxes. Personnel expenses are calculated by the grade of
      technical difficulties, the number of doctors and nurses and the duration of the
      operation. A more precise method to judge the difficulties of the operation seems
      to be necessary. To examine the recent increase in expenses for surgical
      materials, the cooperation of main hospitals authorized by surgical societies
      will be necessary. The prices of surgical operations presented by the Ministry of
      Health and Welfare of Japan correlated well with the prices proposed by the
      Union.

PMID- 10969590
TI  - [Cost analysis on stomach cancer treatment in Japanese hospitals].
AB  - BACKGROUND: In an effort to further the discussion of DRG/PPS, we performed a
      coat analysis on stomach cancer cases in Japanese hospitals. We analyzed
      individual in-patient data (both clinical and financial) to research the amount
      of variation in treatment and costs. METHODS: The data was taken from two
      hospitals. In order to compare the daily cost/revenue of each episode of
      operation/hospitalization, we analyzed the data that was stored for reimbursement
      purposes by using patient ID numbers. We also simulated the cost/revenue in cases
      where the length of stay could be shortened with clinical pathways created by
      Japanese hospitals. RESULTS: (1) There is a common pattern for the
      operation/hospitalization of stomach cancer cases if the patient's condition,
      like severity, is well controlled. However, there is still a noticeable
      difference in the length of stay for patients both before and after the
      operation. (2) Hospitals are currently losing money by having extended patients'
      lengths of stay. Simulation results indicate that hospitals can reduce losses,
      even become profitable, by shortening the patient's length of stay. CONCLUSIONS:
      The potentiality of implementing a standard treatment process and/or a fixed
      payment system, like DRG/PPS, is high, because there is a common a pattern among
      the treatment process. More research must be completed in this area, specifically
      on the significant variations in lengths of stay and the methodology for
      standardization of treatment. Furthermore, clinical outcomes research must also
      be done.

PMID- 10969591
TI  - [Cost accounting for gastrectomy under critical path--the usefulness of direct
      accounting of personnel expenses and a guide to shortening hospital stay].
AB  - In this study, cost accounting was made for a surgical case of gastrectomy
      according to critical path (path) and the economic contribution of the path was
      determined. In addition, changes in the cost percentage with changes in number of
      hospital days were simulated. Basically, cost accounting was done by means of
      cost accounting by departments, which meets the concept of direct cost accounting
      of administered accounts. Personnel expenses were calculated by means of both
      direct and indirect calculations. In the direct method, the total hours personnel
      participated were recorded for calculation. In the indirect method, personnel
      expenses were calculated from the ratio of the income of the surgical department
      to that of other departments. Purchase prices for all materials and drugs used
      were recorded to check buying costs. According to the direct calculating method,
      the personnel expenses came to approximately 300,000 yen, total cost was
      approximately 700,000 yen, and the cost percentage was 59%. According to the
      indirect method, the personnel expenses were approximately 540,000 yen and the
      total cost was approximately 940,000 yen, the cost percentage being 80%. A
      simulation study of changes in the cost with changes in hospital days revealed
      that the cost percentages were assessed to be approximately 53% in 19 hospital
      days and approximately 45% in 12 hospital days.

PMID- 10969592
TI  - [Improvement of the efficiency of the treatment of gastric cancer by the
      standardization of the treatment plan].
AB  - Standardized treatment plan for gastric cancer was established in our department
      by which surgeons and nurses understood the treatment schedules of each gastric
      cancer patient as the common knowledge, and the cooperation of surgeons and
      nurses could be improved. Furthermore, the modality decreased the length of
      hospital stay from 35 +/- 15 days to 24 +/- 8 days, which indicated that the
      number of patients per one bed for one year increased from 10 to 15, and the
      efficiency of the treatment of gastric cancer patients 50% by our system.

PMID- 10969593
TI  - [Critical paths and economical efficiency on cancer therapy].
AB  - The critical paths of cancer patient care are discussed. The number of cancer
      institutes which have introduced critical paths into patient care has been
      increasing in the past few years. The effect of critical paths is to standardize
      the patient care process, shorten the length of the hospital stay of cancer
      patients, reduce the cost of care, have a well-managed cancer care team, and
      satisfy patients with full information on the care schedule. Combined with
      clinical practice guidelines, protocols and algorithms, critical paths are a more
      powerful tool with which to improve the efficiency and quality of cancer patient
      management in hospital care.

PMID- 10969594
TI  - [Issues in the implementation of palliative care--need for a redefinition of the
      outcome of palliative care].
AB  - Due to advances in medical technologies and the increasing range of settings for
      palliative medicine/care, models of palliative care are becoming more diverse.
      The redefinition of models and the outcomes of palliative medicine/care are now
      required. Our evaluation of the settings of palliative care indicates that short
      term hospital-based palliative medicine/care is more effective in the palliation
      of symptoms than home care, while home palliative care is more cost-effective
      than hospital-based palliative care. The outcomes are thus different between
      hospital-based and home palliative medicine/care. Clinical research using
      appropriate outcomes should be beneficial in providing quality palliative care
      effectively and efficiently.

PMID- 10969595
TI  - [Treatment of adult acute lymphoblastic leukemia by KHALL-93--long-term outcome].
AB  - Twelve previously untreated adult patients with acute lymphoblastic leukemia were
      treated with a KHALL-93 regimen. The mean age was 46.9 years. Four patients (1/3)
      were over 60 years old, and 5 were Ph1 positive (42%). The complete remission
      rate was 100%. The 5-year survival was 50% (6/12). The 5-year event-free survival
      was 50% (6/12) in total, 71% (5/7) in Ph1 negative patients, and 63% (5/8) in
      patients younger than 60 years old. These results indicate that a KHALL-93
      regimen is an effective therapy for adult acute lymphoblastic leukemia.

PMID- 10969596
TI  - [Correlation between DNA topoisomerase II alpha expression and sensitivity to
      etoposide in human glioma cell lines].
AB  - The expression of topoisomerase II alpha (Topo II alpha) was investigated in six
      human glioma cell lines as a function of doubling time, cell cycle distribution,
      and sensitivity to an antineoplastic agent, etoposide (ETP). The Topo II alpha
      level was determined by immunohistochemical and flow cytometric studies using
      monoclonal antibody, 8D2, specific for Topo II alpha. In all cell lines, the Topo
      II alpha level correlated directly with sensitivity to ETP, but not with doubling
      time or percentage of cells in any phase of the cell cycle. These findings
      suggest that the cytocidal activity of ETP may be mediated by qualitative and
      quantitative changes in Topo II alpha in human glioma cells. We speculate that
      better knowledge of Topo II alpha expression in surgical specimens may lead to
      more individualized use of ETP in patients with malignant glioma.

PMID- 10969598
TI  - [Analysis of the salvage synthesis within biosynthesis of nucleic acid route in
      colon cancer].
AB  - Orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), uridine
      phosphorylase (UP), dihydropyrimidine dehydrogenase (DPD), and thymidylate
      synthetase (TS) are enzymes which analyze the salvage synthesis within the
      biosynthesis of the nucleic acid route of colon cancer. These enzymes were
      measured in carcinoma and normal tissue. OPRT was 0.065 +/- 0.041 nmol/min/mg
      protein, TP 4.04 +/- 2.81 nmol/min/mg protein, UP 1.79 +/- 1.19 nmol/min/mg
      protein, DPD 23.8 +/- 12.0 pmol/min/mg protein, and TS 6.1 +/- 4.4 pmol/g tissue
      in the normal tissue, and OPRT was 0.199 +/- 0.146 nmol/min/mg protein, TP 13.63
      +/- 6.04 nmol/min/mg protein, UP 5.84 +/- 2.37 nmol/min/mg protein, DPD 22.0 +/-
      13.4 pmol/min/mg protein, TS 16.9 +/- 7.8 pmol/g tissue in the carcinoma. OPRT,
      TP, and UP in the carcinoma mainly existed about 3.06-3.37 times that in normal
      tissue and TS at about 2.77 times. No significant difference was seen in DPD. A
      correlation was found between OPRT in normal tissue and carcinoma. Biosynthesis
      of nucleic acid via salvage synthesis is actively stimulated. Enzymatic activity
      related to uracil was high, and was thought to be closely connected to the growth
      of the cancer.

PMID- 10969597
TI  - [Combination chemotherapy with irinotecan hydrochloride plus carboplatin for
      patients with advanced or recurrent colorectal cancer--a pilot study].
AB  - A pilot study was performed to evaluate the feasibility and efficacy of
      irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of
      advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer
      (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated
      with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks
      followed by a one-week rest. This treatment was repeated until disease
      progression or severe toxic effects were found. The total dose of CPT-11 ranged
      from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022
      (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%)
      diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%),
      thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one
      (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7;
      PD,5). The median survival time of all patients was 405 days from the start of
      chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to
      be longer than that of those with PD (n = 5) (p = 0.06). The median time to
      disease progression was 105 days. These results suggest that this combination
      chemotherapy is feasible and effective in the treatment of advanced or recurrent
      colorectal cancer.

PMID- 10969599
TI  - [Effective chemotherapy with docetaxel in a patient with breast cancer who had
      progressed after high-dose chemotherapy with autologous peripheral blood stem
      cell transplantation (APBSCT)].
AB  - A 39-year-old female underwent mastectomy for breast cancer in December 1995.
      However, two years later, she relapsed with multiple bone metastases. Only a
      partial response was obtained despite tandem high-dose chemotherapy with
      autologous peripheral blood stem cell transplantation (APBSCT). Disease
      progression with bone pain and an increasing in the level of serum NCC-ST439
      occurred 5 months after APBSCT. Salvage chemotherapy with docetaxel 60 mg/m2
      reduced her symptoms, and the level of serum NCC-ST439 decreased to within the
      normal range. Ten cycles of docetaxel administration were repeated without severe
      adverse reactions in an outpatient setting for 10 months. There is little
      information regarding treatment after relapse from APBSCT for breast cancer.
      Docetaxel may be an effective agent for patients in such a setting.

PMID- 10969600
TI  - [A case of effective bisphosphonate therapy of sequential pamidronate and
      incadronate for bone metastases from breast cancer].
AB  - A 55-year-old woman complained of neck pain ten years after undergoing surgery.
      She was diagnosed as having bone metastases and treated using pamidronate therapy
      with doxifluridine, tamoxifen and fadrozole, which was assessed as effective. She
      complained of neck pain 32 months after pamidronate infusion. CT revealed that
      the sclerosis had continued but new lytic lesions were detected in the cervical
      vertebra. Thus, we attempted incadronate and medroxyprogesterone acetate (MPA)
      administration. After 2 months, incadronate therapy with MPA relieved her neck
      pain. CT revealed lytic lesions of cervical vertebra showing sclerosis 3 months
      after this treatment and the sclerosis has continued. Bisphosphonate therapy of
      sequential pamidronate and incadronate with MPA administration is a useful
      treatment for bone metastasis from breast cancer.

PMID- 10969601
TI  - [Lymph node and peritoneum metastases of bile duct cancer responding to
      chronochemotherapy--a case report].
AB  - A 68-year-old man underwent curative pancreaticoduodenectomy for bile duct
      cancer. The histological diagnosis was well differentiated, invasive type tubular
      adenocarcinoma, which was 2 x 2 cm in size and had invaded to the adventitia.
      Lymph node metastasis was not present. The postoperative course was uneventful,
      but lymph node and peritoneum metastases were detected 18 months after surgery.
      Chronochemotherapy of 5-FU (500 mg/body), leucovorin (21 mg/body), mitomycin C (2
      mg/body) and cisplatin (80 mg/body) was performed without significant side
      effects. One course of chronochemotherapy was effective for lymph node and
      peritoneum metastases. The patient died of peritonitis carcinomatosa 10 months
      after recurrence.

PMID- 10969602
TI  - [A patient with gastric cancer with para-aortic lymph node metastases surviving
      for 9 years after effective preoperative chemotherapy and radical operation].
AB  - A 63-year-old male patient with type 3 advanced gastric cancer was referred to
      our hospital. Preoperative examination by CT-scan revealed swollen para-aortic
      lymph nodes and cancer invasion to the pancreas. The patient was treated pre
      operatively with intravenous 5-FU, 500 mg/body/day, continuous infusion for 1
      week. Immediately after the chemotherapy, the patient underwent total
      gastrectomy, splenctomy, left-adrenectomy and resection of the body and tail of
      the pancreas, along with para-aortic lymph node dissection. Microscopic
      examination revealed that the tumor was a moderately differentiated tubular
      adenocarcinoma, which displayed invasion to the pancreas with lymph node
      metastasis up to the level 3 lymph node. Histologically, the effect of
      preoperative chemotherapy showed a grade 2 effect on the main tumor, but a grade
      3 chemotherapeutic effect was observed at the para-aortic lymph nodes. The
      patient has subsequently remained disease free for 9 years. In this case, it is
      considered that the preoperative chemotherapy by 5-FU and potentially curative
      radical operation yielded a good outcome.

PMID- 10969603
TI  - [Two cases of advanced gastric cancer responding to TS-1: a novel oral formation
      of 5-fluorouracil].
AB  - TS-1, a novel oral formation of 5-fluorouracil, consists of 1 M tegafur (5-FU),
      0.4 M CDHP and 1 M Oxo. The response rate in the late phase II study was reported
      as 49% in the patients with advanced gastric cancer. We report two patients with
      metastases from gastric cancer who markedly responded to TS-1. CASE 1: A 74-year
      old man who suffered abdominal tumor was admitted to our hospital. Computed
      tomography (CT) showed advanced gastric cancer with huge liver metastases and
      extensive lymph node metastases. After 120 mg of TS-1 was orally administered for
      12 weeks, CT showed a 77% reduction in the liver metastases. No serious adverse
      reactions were observed. CASE 2: A 66-year-old man had undergone a curative
      distal gastrectomy with D2 lymphadenectomy. One year later, CT showed enlargement
      of paraaortic lymph nodes due to cancer recurrence. There were no metastatic
      lesions in the other organs. After 100 mg of TS-1 was orally administered for 4
      weeks, CT revealed that almost complete reduction of the metastatic nodes was
      obtained. Adverse reactions at grade 2 for leucopenia and anemia were observed.
      In conclusion, TS-1 was effective and well tolerable for patients with advanced
      gastric cancer.

PMID- 10969604
TI  - [A case of metastatic colon carcinoma in which a continuous intrahepatic artery
      infusion of 5-FU leucovorin and cisplatin, and systemic chemotherapy with CPT-11
      was very effective].
AB  - We report a patient with metastatic colon carcinoma who was treated effectively
      with a continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin,
      and systemic chemotherapy with CPT-11. A 50-year-old man was diagnosed as having
      well differentiated adenocarcinoma of the sigmoid colon with multiple liver
      metastases in March, 1997. Left hemicolectomy and subsequent catheterization into
      the common hepatic artery via the gastroduodenal artery were performed in April,
      1997. He was treated with 3 courses of continuous intrahepatic artery-infusion of
      5-FU, Leucovorin and cisplatin, and two courses of systemic chemotherapy with CPT
      11 during hospitalization, followed by 6 courses of a similar intraarterial
      therapy in an outpatient setting. Reinstallation of the catheter into the hepatic
      artery via the femoral artery was performed because of occlusion of the
      reservoir. During the 6th course of intraarterial therapy, diarrhea, nausea, and
      vomiting appeared and angiography revealed a narrowing of the hepatic artery.
      Therefore, the intrahepatic artery-infusion therapy was reinitiated with doses of
      5-FU, Leucovorin and cisplatin reduced to approximately 80%. After 5 courses of
      this therapy, the computed tomography scan showed a marked decrease in the size
      of the metastatic hepatic lesions by 90%, and the serum level of CEA decreased
      from 657.7 ng/ml to 4.5 ng/ml. No severe side effects were seen during the
      treatment. Though multiple lung metastases were indicated during the intrahepatic
      artery-infusion therapy, both the liver and lung metastases have been well
      controlled with continuous intrahepatic artery-infusion chemotherapy and systemic
      chemotherapy. The continuous intrahepatic arterial infusion of 5-FU, leucovorin
      and cisplatin appears to be very effective for the treatment of colon carcinoma
      with liver metastasis without reducing the quality of life.

PMID- 10969605
TI  - [Continual reassessment method (CRM)].
AB  - We discuss the basic concept of the continual reassessment method (CRM) and some
      modifications. The CRM has been proposed as alternatives of traditional cohort
      design for phase I trials in cancer. To focus on the dilemma between ethical
      concern and scientific purpose, we review the requirement for the phase I
      settings and the issues of the traditional cohort design. Then, CRM is introduced
      so that the essential feature is in the sequential (continual) selection of a
      dose level for next patients based on the dose-toxicity relationship and in
      updating the relationship based on patients' response date using Bayesian
      calculation. Finally we discuss both advantages and pitfalls in practice.

PMID- 10969606
TI  - [Role of oxaliplatin in the treatment of colorectal neoplasms].

PMID- 10969607
TI  - [Mechanism of action and pharmacology of new organometallic compounds active in
      the treatment of colorectal neoplasms].

PMID- 10969608
TI  - [Preclinic of the new molecules active on colorectal neoplasms]  .

PMID- 10969609
TI  - [Surgery of carcinoma of the rectum].

PMID- 10969610
TI  - [Adjuvant chemotherapy in cancer of the colon].

PMID- 10969611
TI  - [Adjuvant treatment of carcinoma of the colon].

PMID- 10969612
TI  - [New oxaliplatin-based regimens].

PMID- 10969613
TI  - [Future therapeutic prospectives for the treatment of advanced cancer of the
      colorectum: our experience with oxaliplatin combined with fluorofolates in
      chronoinfusions].

PMID- 10969614
TI  - [New therapeutic approaches in the treatment of advanced stage carcinoma of the
      colorectum].

PMID- 10969615
TI  - [Chronochemotherapy].

PMID- 10969616
TI  - [Treatment of carcinoma of the colorectum. The contribution of oxaliplatin].

PMID- 10969617
TI  - [New options in patients with metastatic cancer of the colon already treated:
      platinum salts].

PMID- 10969618
TI  - [Multimodal treatment of hepatic metastasis of cancer of the colorectum].

PMID- 10969619
TI  - [Tolerance profile of platinum compounds].

PMID- 10969620
TI  - [Therapy of support in patients with carcinoma of the colorectum]  .

PMID- 10969621
TI  - [Palliative care and home support for the oncologic patient].

PMID- 10969622
TI  - Pharmacological management of acute myocardial infarction.
AB  - The routine medical management of patients with acute myocardial infarction (AMI)
      has undergone major changes in the last decade. Several large-scale trials have
      firmly established the effectiveness of thrombolytic therapy, beta blockers, and
      aspirin in the treatment of AMI. The critical issues include reducing myocardial
      oxygen demand and restoring adequate blood supply to the ischemic regions of the
      myocardium. As a result, the ability to intervene in patients with AMI has
      improved significantly. The purpose of this review is to discuss briefly the
      results of major trials of primary and secondary pharmacological intervention
      which had a direct impact on the care of patients with AMI. It concludes with
      current recommendations for the management of patients with AMI.

PMID- 10969623
TI  - Role of echo/Doppler in the diagnosis of pulmonary embolism.
AB  - Echocardiography supplemented with pulsed and continuous wave Doppler facilities
      is a potent diagnostic tool in many cardiovascular disorders. Its potential role
      in the management of patients with suspected pulmonary embolism, though less
      extensively studied, deserves attention. Benefits of echo/Doppler in these
      patients are as follows: (1) Echo/Doppler is a noninvasive, relatively
      inexpensive technique, readily available and repeatable in critically ill
      patients at the bedside. (2) Echo/Doppler provides a number of independent
      parameters related to the pulmonary hemodynamics. These parameters include: (a)
      characteristics of blood flow velocity curves across the right heart valves as
      well as systolic and diastolic time intervals of the right ventricle (b) motion
      pattern of the interventricular septum (c) dimensions of the heart chambers and
      inferior vena cava (d) thickness of the right ventricular free wall (3)
      Echocardiography allows detection of thrombi within right heart chambers or in
      major branches of the pulmonary artery in some patients. (4) Echo/Doppler may
      disclose alternative abnormalities explaining symptoms found in a patient with
      suspected pulmonary embolism such as pericardial disease, myocardial infarction,
      aortic dissection, hypovolemic shock, etc.

PMID- 10969624
TI  - New approaches to noninvasive assessment of pulmonary artery pressure.
AB  - Direct measurement of pulmonary artery pressure (PAP) was performed in 36
      patients; right ventricular (RV) isovolumic relaxation time (IRT) and RV systolic
      output acceleration time (AcT) values were assessed by pulsed Doppler and 2-M
      echocardiography. There was a fairly good correlation between RV IRT and systolic
      PAP (r = 0.898; SEE = 7.8 mmHg) and a somewhat weaker one between RV AcT and
      systolic PAP (r = -0.880; SEE = 8.37 mmHg). Correlation coefficients were the
      highest between systolic PAP and the [formula: see text] (r = 0.972; SEE = 4.14),
      and also between mean PAP and the 10-RV AcT/100 predictor: y = 158x + 6.7 (r =
      0.951; SEE = 3.48 mmHg). With +/- 5 mmHg deviations, systolic PAP measurements
      were accurate in 78% and those of mean PAP in 98% of the patients. The double
      blind assessment of the reproducibility of the suggested noninvasive PAP
      measurement was performed in 18 subsequent patients; the interstudy variability
      of the measurement was 0.88 +/- 0.94 mmHg and 1.22 +/- 1.23 mmHg (p > 0.05),
      whereas interobserver variability was 1.90 +/- 1.70 mmHg and 1.67 +/- 1.63 mmHg,
      respectively (p > 0.05). Thus, a combined use of the most informative intervals
      of RV cycle--IRT and AcT--contributes to the accuracy of noninvasive PAP
      measurement.

PMID- 10969625
TI  - Pulmonary artery diastolic pressure: a simultaneous Doppler echocardiography and
      catheterization study.
AB  - Pulmonary hypertension is an important determinant of the clinical presentation
      of and surgical approach to patients with heart disease. To confirm the utility
      of continuous wave Doppler echocardiography in assessing the pulmonary artery
      diastolic pressure in patients with pulmonary regurgitation, 51 patients
      representing the wide hemodynamic spectrum of pulmonary artery pressure underwent
      simultaneous determination of pulmonary artery diastolic pressure by continuous
      wave Doppler echocardiography and cardiac catheterization. Pulmonary artery
      diastolic pressure was estimated from the Doppler recordings by the end-diastolic
      pressure gradient obtained by the modified Bernoulli equation plus the estimated
      right atrial pressure. A correlation was observed (r = 0.935, SEE = 7.4 mmHg)
      between Doppler and catheterization pulmonary artery diastolic pressure. In
      addition, comparison between the mean diastolic pressure gradient across the
      pulmonary valve by Doppler and pulmonary artery diastolic pressure at
      catheterization yielded a high correlation (r = 0.947, SEE = 5.1 mmHg). These
      data demonstrate that continuous wave Doppler echocardiography is a useful
      noninvasive technique for evaluating the pulmonary artery diastolic pressure in
      patients with pulmonary regurgitation.

PMID- 10969626
TI  - Coronary angiography using 4-French preformed catheters--percutaneous brachial
      approach.
AB  - 4-French performed catheter systems were developed for coronary angiography.
      After several new technical features were introduced, these catheters were
      applied in 384 outpatients between January 1989 and December 1989. Diagnostic
      coronary angiography was performed in all cases without major complications. In
      the left coronary artery, 4.0 cm left Judkins catheters were generally used;
      however, 3.5 cm left Judkins catheters were used if the patient was < or = 164 cm
      tall and left Amplatz catheters were employed for those > or = 165 cm tall.
      Although 4.0 cm right Judkins catheters were mainly used for right coronary
      arteries, there were no predictive factors for subsequent catheter selection.
      This technique is believed to be suited to meet the increasing demand for
      coronary angiography.

PMID- 10969627
TI  - Comparison of clinical, morphological, and prognostic features in hypertrophic
      cardiomyopathy between Japanese and western patients.
AB  - Apical hypertrophic cardiomyopathy appears to be more common in Japan than in the
      West. Explanations for this difference include variable methods and criteria for
      the diagnosis. To assess morphological, clinical, and prognostic differences, 45
      consecutive Japanese and 45 age- and gender-matched Western patients with
      hypertrophic cardiomyopathy were evaluated in two referral institutions by the
      same individuals. The diagnosis of hypertrophic cardiomyopathy was based on the
      echocardiographic demonstration of unexplained left ventricular hypertrophy.
      Patients were aged 8 to 64 years (mean 50); there were 66 males and 24 females.
      The pattern of left ventricular hypertrophy was similar in Japanese and Western
      patients: asymmetric septal 64 vs. 76%, concentric 22 vs. 13%, and apical 13 vs.
      11% (p = NS). The incidence of an echocardiographic or Doppler calculated left
      ventricular gradient of > 30 mmHg was similar (11 vs. 18%; p = NS). The maximal
      left ventricular wall thickness was greater in Western patients (23 +/- 7 vs. 20
      +/- 4 mm; p = 0.03), but was not different when adjusted for body surface area.
      Clinical features including incidence of family history and ventricular
      tachycardia during 24-h ambulatory electrocardiography were similar. During
      follow-up (4.9 +/- 4.0 years for Western vs. 4.4 +/- 2.0 years for Japanese),
      disease-related mortality was worse in Western patients (p < 0.05; 10 versus 2
      patients). This evaluation, using the same diagnostic methods and criteria,
      reveals a worse prognosis in Western patients despite a similar clinical and
      morphological spectrum of hypertrophic cardiomyopathy.

PMID- 10969628
TI  - Syncope and seizures of psychogenic origin: identification with head-upright tilt
      table testing.
AB  - Psychogenic seizures and psychogenic syncope are common disorders but are
      difficult to identify. Head-upright tilt table testing has emerged as a promising
      means of evaluating vasovagally mediated syncope and convulsive syncope. Of a
      total of 42 patients evaluated by head-up tilt for recurrent syncope and 10
      evaluated for recurrent idiopathic seizures, a total of 5 patients experienced
      syncope and 3 had tonic-clonic seizure activity unaccompanied by any significant
      changes in blood pressure, heart rate, transcranial Doppler cerebral blood flow
      velocity, and electroencephalographic monitoring. Psychiatric evaluation revealed
      that seven patients suffered from conversion reactions and one from probable
      malingering. We conclude that patients who pass out or convulse during head
      upright tilt without any change in physiologic parameters can be presumed
      psychogenic in origin and may be referred for psychiatric evaluation without
      further expensive diagnostic studies.

PMID- 10969629
TI  - Diastolic left ventricular function after renal transplantation in patients with
      normal and hypertrophied myocardium.
AB  - While diastolic left ventricular (LV) dysfunction is frequent and associated with
      cardiovascular complications in end-stage renal disease treated with dialysis,
      controversial information exists on diastolic LV function after renal
      transplantation. Therefore, Doppler echocardiographic parameters of LV diastolic
      filling were analyzed in 17 transplanted patients with normal LV mass (< 150
      g/m2; mean: 128 +/- 17 g/m2) and 24 transplanted patients with LV hypertrophy (>
      150 g/m2; mean: 197 +/- 36 g/m2) and compared with 28 normal controls without and
      11 controls with LV hypertrophy. Mean age (normal vs. increased LV mass: 46 +/-
      13 vs. 48 +/- 11 years; p = NS) and transplantation duration (60 +/- 35 vs. 50 +/
      37 months; p = NS) were comparable between renal patients, while systolic blood
      pressure (136 +/- 12 vs. 149 +/- 14 mmHg; p < 0.02) and serum creatinine (1.55 +/
      0.45 vs. 1.98 +/- 0.76 mg/dl; p < 0.05) were higher in patients with than
      without LV hypertrophy. In transplanted patients with LV hypertrophy, peak
      early/atrial filling velocity ratios were decreased (1.17 +/- 0.34 vs. 0.94 +/-
      0.34; p < 0.05), mean atrial filling fractions were increased (37 +/- 7% vs. 42
      +/- 7%; p < 0.05), and isovolumic relaxation periods were prolonged (86 +/- 23
      vs. 106 +/- 26 ms; p < 0.02) compared with transplanted patients with normal LV
      mass. The frequency of pathologic peak early/atrial filling velocity ratios (12
      vs. 42%; p < 0.05), atrial filling fractions (12 vs. 25%; p = NS) and isovolumic
      relaxation periods (6 vs. 29%; p = NS) was higher in transplanted patients with
      than without LV hypertrophy. Individual ratios of peak early/atrial filling
      velocity were inversely correlated with age in transplanted patients with normal
      LV mass (p < 0.002), and atrial filling fractions were correlated with LV mass
      index in transplanted patients with LV hypertrophy (p < 0.01). Diastolic LV
      function was comparable in both groups of transplanted patients with their
      corresponding non-renal controls. It is concluded that, in transplanted patients,
      diastolic LV filling is comparable to nonrenal controls; it is age-dependent in
      patients with normal LV mass and mass-dependent in those with LV hypertrophy.

PMID- 10969630
TI  - Incidence of sudden athletic deaths between 1985 and 1990 in Marion County,
      Indiana.
AB  - Relatively little information is available concerning the incidence of sudden
      death in athletes in the United States. The present study provides annual
      incidence rates of sudden athletic deaths in Marion County, Indiana, home of
      Indianapolis, the "amateur sports capital of the world." The overall incidence
      was 0.04% (18 athletic deaths in 44,481 forensic necropsies). This incidence
      varied slightly over the 6-year study period: 1985 (0.06%), 1986 (0.03%), 1987
      (0.04%), 1988 (0.09%), 1989 (0%), 1990 (0.01%). Of the 18 sudden athletic deaths,
      88% were cardiac in origin. A retrospective analysis of preparticipation
      screening efforts suggests that most of the cardiac conditions responsible for
      death could have been detected.

PMID- 10969631
TI  - Congenital absence of pericardium as unusual cause of T wave abnormalities in a
      young athlete.
AB  - The congenital absence of pericardium is a rare condition which may determine
      electrocardiographic ST-T abnormalities. The case of a 16-year-old athlete who
      presented T-wave abnormalities at standard electrocardiogram performed during a
      physical checkup is reported. Ventricular repolarization tended to normalize
      during exercise and in right lateral decubitus. Chest x-ray and echocardiography
      showed typical signs of complete absence of the left pericardium. The definite
      diagnosis was made by computer tomography (CT) scan. The importance of a complete
      investigation of athletes with T-wave abnormalities is emphasized. Diagnostic and
      therapeutic features of the congenital absence of pericardium are discussed.

PMID- 10969632
TI  - Shoshin beriberi in an AIDS patient with end-stage renal disease.
AB  - Asymptomatic cardiomegaly and subsequent fulminant pulmonary edema developed in
      an AIDS patient with end-stage renal disease who had no prior history of cardiac
      disease. Intravenous thiamine administration led to dramatic resolution of both
      obtundation and cardiovascular collapse within 4 hours. Prolonged thiamine
      administration led to decreased cardiomegaly. These findings are consistent with
      Shoshin beriberi.

PMID- 10969633
TI  - Moricizine-induced proarrhythmia.
AB  - Moricizine is a Class I antiarrhythmic drug currently approved for the treatment
      of life-threatening ventricular arrhythmias. The drug has received significant
      attention because of its role in the Cardiac Arrhythmia Suppression Trial.
      Previous data suggested that the agent has a relatively low proarrhythmic
      potential. This may lead clinicians to use the drug empirically for less
      significant ventricular arrhythmias. We report a case of life-threatening late
      proarrhythmia caused by moricizine and comment on our experience with this agent.
      We feel that this drug has significant proarrhythmic potential and should not be
      used empirically to treat ventricular ectopy especially in patients with
      underlying structural heart disease.

PMID- 10969634
TI  - Carey F. Coombs.

PMID- 10969635
TI  - Electrophysiological effects of blocking and stimulating the opioid system in
      patients with unexplained heart palpitations.

PMID- 10969637
TI  - Depression, service need, and use in vulnerable populations.
AB  - Health care reform has created opportunities for mental health nurses to develop
      innovative health care delivery models to provide integrated behavioral health
      and primary health care. A community health analysis is one method to ensure
      appropriate services are planned. This study examined the health care services
      most needed and those used by depressed and nondepressed participants (N = 231),
      and their satisfaction with these services. Individual and system characteristics
      were examined using a framework developed by Anderson and Aday. Significant
      differences were found between the 2 groups for predisposing characteristics,
      enabling characteristics, need for care, service use, and satisfaction with
      services.

PMID- 10969636
TI  - The Psychogeriatric Assessment and Treatment in City Housing (PATCH) program for
      elders with mental illness in public housing: getting through the crack in the
      door.
AB  - Psychogeriatric Assessment and Treatment in City Housing (PATCH) is an outreach
      program targeting elderly public housing residents who need mental health care.
      The PATCH model relies on educating housing personnel to serve as case finders,
      providing in-home psychiatric evaluation and treatment, and addressing medical
      and social comorbidities through case management by psychiatric nurses. An
      examination of PATCH interventions suggests that the program's success is due to
      its emphasis on: (1) educating patients, housing personnel, and caregivers about
      patients' illnesses and need for treatment and support; and (2) coordinating care
      among housing staff members, patients' caregivers and their primary medical
      providers.

PMID- 10969638
TI  - The interface of anthropology and nursing guiding culturally competent care in
      psychiatric nursing.
AB  - Nurses and all health care providers are called on to involve patients and
      families in health care decision-making and to accommodate culturally diverse
      populations. This article describes the Interface of Anthropology and Nursing
      Model (IAN), which is derived from the works of Kleinman and Peplau, classical
      theorists from anthropology and nursing, respectively. This model provides a
      framework for nurses to uncover cultural information through the elicitation,
      analysis, transfer, restructure, and feedback of explanatory models within the
      interpersonal nurse-patient relationship. Such integration of theory enhances a
      holistic nursing practice incorporating good communication, mutual decision
      making, and fostering patient agency.

PMID- 10969639
TI  - Promoting the mental health of elderly African Americans: a case illustration.
AB  - Promoting mental health in an illness-oriented health care delivery system is
      challenging. Health promotion from a holistic perspective requires that mental
      health be viewed as important as physical health. The mental health needs of the
      elderly are numerous and often not addressed during routine visits for primary
      health care. Research consistently reports that elderly African Americans are not
      equal participants in the formal health care system. Consequently, promoting
      mental health in the African American elderly is a challenge made even more
      complicated because of this group's limited access to and use of mental health
      care services. Promoting the health of African Americans confronts many
      traditional values and practices of health care institutions and mental health
      practice. Therefore, health care providers must be innovative and creative to
      facilitate mental health promotion in this population of clients. The authors
      suggest that the Revised Health Promotion Model can serve as a framework for
      guiding the mental health care of elderly African Americans. Aspects of the model
      are particularly relevant for this population. The case of an elderly Black woman
      is presented as an illustration of ways in which the model may be applied with
      many cultural nuances.

PMID- 10969641
TI  - Recruitment and retention of African American elders into community-based
      research: lessons learned.

PMID- 10969640
TI  - Depression and burn wounds.
AB  - The biopsychosocial impact of a burn injury on the individual hospitalized for
      severe burn wounds begins at the moment of injury and extends throughout that
      person's life. Medical and emotional problems do not exist in clinical isolation
      but instead interact to confound and complicate treatment outcomes, accentuating
      the importance of providing optimal treatment of patients' medical illnesses
      without neglecting their mental distress. Identifying, and responding to, the
      signs and symptoms of depression is integral to the burn patient's recovery and
      rehabilitation.

PMID- 10969642
TI  - Medicine at the turn of the century.

PMID- 10969643
TI  - A call to leadership: Project Access--helping the uninsured community by
      community.

PMID- 10969644
TI  - Ischemic preconditioning: how close are we to therapeutic implementation?

PMID- 10969646
TI  - Bronchial and bronchovascular sleeve resection for treatment of central lung
      tumors.
AB  - BACKGROUND: To improve postoperative pulmonary reserve, we have employed
      parenchyma-sparing resections for central lung tumors irrespective of pulmonary
      function. The results of lobectomy, pneumonectomy, and sleeve resection were
      analyzed retrospectively. METHODS: From October 1995 to June 1999, 422 typical
      lung resections were performed for lung cancer. Of these, 301 were lobectomies
      (group I), 81 were sleeve resections (group II), and 40 were pneumonectomies
      (group III). RESULTS: Operative mortality was 2% in group I, 1.2% in group II,
      and 7.5% in group III (group I and II vs. group III, p<0.03). Mean time of
      intubation was 1.0+/-4.1 days in group I, 0.9+/-1.3 days in group II, and 3.6+/
      11.2 days in group III (groups I and II vs. group III, p<0.01). The incidence of
      bronchial complications was 1.3% in group I, none in group II, and 7.5% in group
      III (group I and II vs group III, p<0.001). After 2 years, survival was 64% in
      group I, 61.9% in group II, and 56.1% in group III (p = NS). Freedom from local
      disease recurrence was 92.1% in group I, 95.7% in group II, and 90.9% in group
      III after 2 years (p = NS). CONCLUSIONS: Sleeve resection is a useful surgical
      option for the treatment of central lung tumors, thus avoiding pneumonectomy with
      its associated risks. Morbidity, early mortality, long-term survival, and
      recurrence of disease after sleeve resection are similar to those seen after
      lobectomy.

PMID- 10969645
TI  - Mediastinal lymph node dissection improves survival in patients with stages II
      and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group.
AB  - BACKGROUND: Mediastinal lymph node dissection (MLND) is an integral part of
      surgery for non-small cell lung cancer (NSCLC). To compare the impact of
      systematic sampling (SS) and complete MLND on the identification of mediastinal
      lymph node metastases and patient survival, the Eastern Cooperative Oncology
      Group (ECOG) stratified patients by type of MLND before participation in ECOG
      3590 (a randomized prospective trial of adjuvant therapy in patients with
      completely resected stages II and IIIa NSCLC). METHODS: Eligibility requirements
      for study entry included a thorough investigation of the mediastinal lymph nodes
      with either SS or complete MLND. The former was defined as removal of at least
      one lymph node at levels 4, 7, and 10 during a right thoracotomy and at levels 5
      and/or 6 and 7 during a left thoracotomy, while the latter required complete
      removal of all lymph nodes at those levels. RESULTS: Three hundred seventy-three
      eligible patients were accrued to the study. Among the 187 patients who underwent
      SS, N1 disease was identified in 40% and N2 disease in 60%. This was not
      significantly different than the 41% of N1 disease and 59% of N2 disease found
      among the 186 patients who underwent complete MLND. Among the 222 patients with
      N2 metastases, multiple levels of N2 disease were documented in 30% of patients
      who underwent complete MLND and in 12% of patients who had SS (p = 0.001). Median
      survival was 57.5 months for those patients who had undergone complete MLND and
      29.2 months for those patients who had SS (p = 0.004). However, the survival
      advantage was limited to patients with right lung tumors (66.4 months vs 24.5
      months, p<0.001). CONCLUSIONS: In this nonrandomized comparison, SS was as
      efficacious as complete MLND in staging patients with NSCLC. However, complete
      MLND identified significantly more levels of N2 disease. Furthermore, complete
      MLND was associated with improved survival with right NSCLC when compared with
      SS.

PMID- 10969647
TI  - Median sternotomy versus thoracotomy to resect primary lung cancer: analysis of
      815 cases.
AB  - BACKGROUND: We sought to determine if median sternotomy (MS) is an equivalent
      incision to thoracotomy (TH) in the treatment of primary pulmonary carcinoma.
      METHODS: We followed 801 patients undergoing 815 operations for primary lung
      carcinoma in a computer registry; 447 had MS, 368 had TH. RESULTS: Both groups
      were similar in preoperative risk assessment. Complete staging lymph node
      dissections were performed in 42% of MS patients and 17% of TH patients.
      Operative mortality (3.8% for MS, 3.3% for TH) and postoperative complications
      were similar. MS patients had a shorter postoperative hospital stay (7.5 days vs.
      8.2 days). One hundred thirty-nine underwent pneumonectomy. Operative mortality
      was 12.5% for MS and 10.4% for TS (p = NS). Five hundred eighty-one underwent
      lobectomy with an operative mortality of 2.1% for MS and 2.0% for TH. Mean length
      of stay for MS lobectomy was 7.5 days compared with 8.5 days for TH (p = 0.06).
      Follow-up was 89% through 1998, comprising 1,339 MS and 1,463 TH patient-years.
      Survival for stage I at 5 and 10 years, respectively, was 51% and 34% for MS vs
      54% and 32% for TH (p = NS). Survival for other stages was also similar.
      CONCLUSIONS: Median sternotomy provides more complete staging, shorter
      postoperative hospitalization, and better patient acceptance with equivalent
      operative and long-term survival when compared with thoracotomy. Concerns
      regarding increased wound infections in MS patients appear unfounded.

PMID- 10969648
TI  - Surgery for pulmonary metastases from colorectal carcinoma.
AB  - BACKGROUND: This study aims to clarify which patients would benefit by surgery
      for pulmonary metastases from colorectal carcinoma. METHODS: A retrospective
      study was undertaken in 25 patients who had undergone complete resection. In all
      cases, prethoracotomy carcinoembryonic antigen (CEA) level was measured and
      mediastinal or hilar lymph nodes were histologically examined. RESULTS: Overall 5
      year survival was 39.2%. The 5-year survival rate for patients with a normal CEA
      level was 61.1%, as compared with 19.0% for patients with an elevated CEA level
      (p = 0.0423). The 5-year survival rate for patients without a lymph node
      metastasis was 49.5%, as compared with 14.3% for patients with a lymph node
      metastasis (p = 0.0032). No lymph node metastasis was a predictor of longer
      survival by univariate and multivariate analyses. The primary site, disease-free
      interval, and number and size of the metastasis were not significant prognostic
      factors. CONCLUSIONS: A resection for pulmonary metastasis from colorectal
      carcinoma is effective in patients with a normal CEA level and without a lymph
      node metastasis.

PMID- 10969649
TI  - Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung
      cancer.
AB  - BACKGROUND: Lymph node metastases are the most significant prognostic factor in
      localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be
      detected. Identification of the first nodal drainage site (sentinel node) may
      improve detection of metastatic nodes. We performed intraoperative Technetium 99m
      sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS:
      Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were
      enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After
      dissection, scintographic readings of both the primary tumor and lymph nodes were
      obtained with a handheld gamma counter. Resection with mediastinal node
      dissection was performed and findings were correlated with histologic
      examination. RESULTS: Seven of the 52 patients did not have NSCLC (5 benign
      lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had
      NSCLC completely resected. Mean time from injection of the radionucleide to
      identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven
      patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37
      SNs (94%) were classified as true positive with no metastases found in other
      intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately
      identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients
      (22%). CONCLUSIONS: Intraoperative SN mapping with Tc-99 is an accurate way to
      identify the first site of potential nodal metastases of NSCLC. This method may
      improve the precision of pathologic staging and limit the need for mediastinal
      node dissection in selected patients.

PMID- 10969650
TI  - Remediastinoscopy after induction chemotherapy in non-small cell lung cancer.
AB  - BACKGROUND: This study was undertaken to evaluate the technical feasibility and
      the sensitivity, specificity, and accuracy of remediastinoscopy in restaging N2
      bronchogenic carcinoma treated with neoadjuvant chemotherapy. METHODS: Patients
      presenting mediastinal lymph node involvement at mediastinoscopy received three
      or four cycles of neoadjuvant chemotherapy with mitomycin, iphosphamide, and
      cisplatin or cisplatin and gemcitabine. If there was no disease progression,
      these patients underwent remediastinoscopy and, if no residual extracapsular
      involvement or N3 disease was found, a thoracotomy was then carried out. RESULTS:
      Twenty-four patients underwent remediastinoscopy. In 12 (50%) remediastinoscopy
      was positive. The 12 remaining patients were operated on and the tumors resected:
      5 pneumonectomies and 7 lobectomies. Lymphadenectomy specimens showed residual
      disease in mediastinal lymph nodes in 5 patients (pN2) and hilar lymph nodes in 1
      patient (pN1). The other 6 patients were free of nodal disease, and 4 of them
      presented no involvement at lung level either. The sensitivity, specificity, and
      accuracy of remediastinoscopy were 0.7, 1, and 0.8, respectively. CONCLUSIONS:
      Remediastinoscopy is a technically feasible staging tool with high diagnostic
      accuracy that is useful in the selection of patients who can be served best by
      complete resection after neoadjuvant chemotherapy.

PMID- 10969651
TI  - Anastomotic complications after bronchoplastic procedures for nonsmall cell lung
      cancer.
AB  - BACKGROUND: Anastomotic complications associated with bronchoplastic procedures
      cannot be completely avoided despite the improvements made in surgical techniques
      and suture materials. Thus, the present study attempted to clearly define the
      significant factors influencing anastomotic complications. METHODS: Between 1978
      and 1998, 47 patients with primary nonsmall cell lung cancer underwent
      bronchoplastic procedures. The incidences of anastomotic complications were
      calculated according to each of the following clinical factors: primary site,
      age, pathologic type, pT factor, pN factor, pulmonary arterioplasty, surgical
      procedure, suture material, coverage of the anastomotic line, positive resection
      margin, and preoperative chemotherapy. The results were analyzed using univariate
      and multiple logistic regression analysis. RESULTS: Anastomotic complications
      occurred in 8 patients. Four had anastomotic dehiscence and 4 had stenosis. Of
      these 8 patients, the resection margin was diagnosed as being positive in 6
      patients. Three showed metastasis of the most distal mediastinal lymph node
      whereas the others had a residual tumor at the bronchial resection margin.
      According to multiple logistic regression analysis, only pN factor (p = 0.04) and
      positive resection margin (p = 0.02) had a significant influence on the
      complications. CONCLUSIONS: Thus, pN2 patients, especially those with metastasis
      of the most distal mediastinal lymph node and patients with a residual tumor at
      the bronchial resection margin, have a significantly higher risk of anastomotic
      complications.

PMID- 10969652
TI  - Expression of human telomerase subunit genes in primary lung cancer and its
      clinical significance.
AB  - BACKGROUND: Three major components of human telomerase, RNA component (hTERC),
      telomerase-associated protein (TEP1), and catalytic subunit (hTERT) have been
      cloned recently. The aim of this study was to examine the expression of these
      genes and to search for clinical usefulness. METHODS: Expression of these genes
      was evaluated by reverse transcription-polymerase chain reaction in 92 human lung
      cancers and in 32 non-neoplastic lung tissues. In 15 patients, both telomerase
      activity by telomeric repeat amplification protocol assay and expression were
      evaluated. RESULTS: hTERT expression was best associated with telomerase activity
      with a concordance of 77%. In 92 lung cancer tissues, hTERC, TEP1, and hTERT were
      expressed in 100%, 93%, and 89%, respectively. Whereas most adjacent non
      neoplastic lung tissues expressed hTERC and TEP1 (94% and 100%, respectively),
      hTERT was detected in only 1 of 32 normal lungs. However, there was no
      relationship between hTERT expression and clinicopathologic features.
      CONCLUSIONS: hTERT expression can be a surrogate for telomerase activity that may
      serve as a novel biomarker of lung cancer with high specificity and sensitivity.

PMID- 10969653
TI  - Gene-modified PA1-STK cells home to tumor sites in patients with malignant
      pleural mesothelioma.
AB  - BACKGROUND: Malignant mesothelioma is an uncommon but lethal cancer of increasing
      incidence, particularly among patients with a history of exposure to asbestos.
      Although numerous treatments have been employed, including chemotherapy,
      radiation therapy, surgical resection, and combinations of the above, no
      satisfactory treatment yet exists, and affected patients will die of this
      disease, usually within 12 months. Gene-based therapies constitute a new approach
      that offers hope of improved control of these tumors while being associated with
      less morbidity than conventional chemotherapeutic or surgical regimens. We
      demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a
      phenomenon that is required for optimal exertion of this therapeutic concept.
      METHODS: Gene-modified ovarian cancer cells expressing the thymidine-kinase gene
      (PA1-STK) were radiolabeled with 99Tc and infused into the pleural space of 4
      patients with malignant pleural mesothelioma, then scanned to determine
      distribution of the cells. RESULTS: PA1-STK cells recognized and adhered
      preferentially to mesothelioma lining the chest wall. CONCLUSIONS: Cell-based
      "suicide gene" therapy utilizing the "bystander effect" with the gene-modified
      ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We
      have shown that this trafficking and homing of the therapeutic cells to the
      intrapleural tumor sites, a requirement for success with this novel therapeutic
      concept, is also valid in humans.

PMID- 10969654
TI  - Primary spontaneous pneumothorax: one-stage treatment by bilateral
      videothoracoscopy.
AB  - BACKGROUND: The goal of the study was to report our 7-year experience with single
      stage bilateral videothoracoscopy for bleb excision and pleural abrasion in
      patients suffering primary spontaneous pneumothorax. METHODS: From November 1992
      through June 1999, 12 men were operated on in our department. Preoperative chest
      computed tomographic scans were obtained for all patients. Operative indications
      included simultaneous bilateral pneumothorax (n = 2), contralateral recurrence (n
      = 1), ipsilateral recurrence with contralateral blebs or bullae, and job
      restrictions (n = 9). RESULTS: Mean age at operation was 26+/-6 years. All
      patients had multiple blebs or bullae located in upper lobes, and 4 patients
      (33%) had pleural adhesions. All blebs or bullae were resected at operation. The
      mean number of staple cartridges was 5 per patient (range, 3 to 8). All patients
      had bilateral pleurabrasion. There were no perioperative complications and no
      conversion to thoracotomy. The mean operative time was 168+/-17 minutes (range,
      140 to 190 minutes). The mean drainage time was 5 days (range, 4 to 26 days) and
      the mean hospital stay was 7.7+/-1.4 days for 11 of 12 patients. Postoperative
      complications included prolonged air leak (16.5%), incomplete lung reexpansion
      (25%), and pleural effusion (8.5%). One patient required reoperation on the right
      side through transaxillary thoracotomy within 1 month of videothoracoscopy for
      pleurodesis failure. Follow-up was 100% complete. Mean follow-up is 50+/-34
      months (range, 9 to 88 months) and no patient has had recurrence of pneumothorax.
      All patients except one returned to full occupational activity within 5 weeks of
      surgery. CONCLUSIONS: Single-stage bilateral videothoracoscopy for bilateral bleb
      excision and pleurabrasion is a safe procedure that does not result in major
      complications and provides excellent long-term results. This approach could be
      considered in young patients with bilateral primary spontaneous pneumothorax, or
      in those requiring radical therapy for the prevention of ipsilateral and
      contralateral recurrences.

PMID- 10969655
TI  - Thoracoscopic esophageal mobilization for pharyngolaryngoesophagectomy.
AB  - BACKGROUND: Pharyngolaryngoesophagectomy (PLE) for hypopharyngeal cancers and
      tumors of the cervical esophagus is a procedure of significant morbidity and
      mortality. Conventional esophageal mobilization is performed with the transhiatal
      dissection technique. Thoracoscopic esophageal mobilization is tested as an
      alternative to determine whether surgical outcome can be improved. METHODS: From
      1994 to 1998, thoracoscopic mobilization was carried out in 30 consecutive
      patients who underwent PLE (PLE-TS). This was compared to a historical cohort of
      30 patients who had PLE with transhiatal mobilization (PLE-TH). RESULTS: In PLE
      TS, thoracoscopic esophageal mobilization was successful in 28 patients (93%).
      Median blood loss was 700 mL (range, 164 to 3,000 mL) compared to 1,000 mL
      (range, 400 to 2,200 mL) in group PLE-TH, p = 0.21. Thoracoscopy time was 90
      minutes (range, 60 to 180 minutes). Total operating time were 392 minutes (range,
      180 to 570 minutes) and 300 minutes (range, 150 to 550 minutes) in PLE-TS and PLE
      TH, respectively (p = 0.03). Major pulmonary complications occurred in 7 (23%)
      and 8 (27%) patients in PLE-TS and PLE-TH, respectively (p = 0.77). Cardiac
      complications occurred in 7 (23%) and 5 (17%) patients in PLE-TS and PLE-TH,
      respectively (p = 0.52). Thirty-day mortality rates were 3.3% and 10% (p = 0.6)
      and hospital mortality rates were 13% and 17%, (p = 1.0). CONCLUSIONS:
      Thoracoscopy was safe and feasible. Morbidity and mortality after PLE was not
      significantly reduced. The theoretical advantage offered by thoracoscopy may be
      offset by the lengthened time of one-lung anesthesia.

PMID- 10969656
TI  - Platelet activating factor acetylhydrolase decreases lung reperfusion injury.
AB  - BACKGROUND: Ischemia-reperfusion injury involves free radical production,
      polymorphonuclear neutrophil chemotaxis/degranulation, and production of
      proteolytic enzymes, complement components, coagulation factors, and cytokines.
      Activated polymorphonuclear neutrophils, endothelial cells, and macrophages
      produce platelet activating factor, which further promotes these inflammatory
      reactions. The recently cloned plasma form of platelet activating factor
      acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading
      platelet activating factor. We evaluated the effects of PAF-AH in an isolated
      perfused rat lung model by adding it to the flush solutions or to the reperfusion
      blood. METHODS: Rat lungs were isolated, flushed with EuroCollins (EC) or
      University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours,
      and reperfused using a cross-circulating syngeneic support rat. During
      reperfusion, oxygenation, compliance, and capillary filtration coefficient were
      calculated. There were four groups in the study; group I (control) had no PAF-AH
      added, group II had PAF-AH added to the flush solution, group III had PAF-AH
      added to reperfusion blood, and group IV had PAF-AH added to both flush solution
      and reperfusion blood. RESULTS: After 6 hours of storage, oxygenation,
      compliance, and capillary filtration coefficient significantly improved for EC in
      group IV. For UW, oxygenation improved in group IV whereas compliance improved in
      groups II, III, and IV. After 12 hours of storage, compliance improved for EC in
      group IV and capillary filtration coefficient improved in groups III and IV. For
      UW, oxygenation and compliance improved in groups II and IV, whereas capillary
      filtration coefficient improved in group IV. CONCLUSIONS: Addition of PAF-AH to
      intracellular organ preservation solutions and to the blood reperfusate
      significantly improves postreperfusion oxygenation and compliance, and reduces
      lung capillary permeability.

PMID- 10969657
TI  - Is general thoracic surgical practice evidence based?
AB  - BACKGROUND: In evidence-based medicine clinical decisions are based on
      experimental evidence of treatment efficacy. There are no data on the extent to
      which general thoracic surgical practice is evidence based. METHODS: A list of 50
      thoracic surgical treatments was derived from the operating room log of one
      surgeon practicing at both a tertiary care cancer center and an affiliated
      community general hospital. Minor diagnostic procedures and procedures performed
      as part of experimental protocols were excluded. For each treatment a Medline
      search was done to obtain the best published evidence supporting the treatment's
      efficacy. The evidence was then placed in one of three categories developed by
      the Oxford Centre for Evidence-Based Medicine: (1) evidence from randomized
      controlled trials (RCTs); (2) convincing non-experimental evidence; and (3)
      interventions without substantial evidence. RESULTS: Category 1 evidence
      supported 7 of 50 thoracic surgical treatments. Category 2 evidence supported 32
      treatments, and 11 treatments were without substantial supportive evidence.
      CONCLUSIONS: The majority of commonly performed general thoracic surgical
      procedures are supported by nonexperimental evidence. Although there are many
      obstacles to the performance of surgical randomized controlled trials, the
      limitations of nonrandomized studies are such that continued emphasis on
      randomized controlled trials in general thoracic surgery is warranted. This study
      could serve as a baseline reference for future assessments of evidence-based
      medicine in general thoracic surgical practice.

PMID- 10969658
TI  - Decreasing mortality for aortic and mitral valve surgery in Northern New England.
      Northern New England Cardiovascular Disease Study Group.
AB  - BACKGROUND: Although numerous reports have documented declining mortality rates
      associated with coronary artery bypass surgery in recent years, it is unknown
      whether similar trends have occurred with valve surgery during this time.
      METHODS: We conducted a regional, prospective study to assess trends in patient
      casemix and in-hospital mortality rates over time with aortic valve replacement
      (AVR), mitral valve replacement (MVR), and mitral valve repair. Data were
      collected from all patients undergoing AVR (n = 2,596), MVR (n = 759), or mitral
      valve repair (n = 522) in Northern New England between January 1992 and December
      1997. Logistic regression was used to identify significant predictors of in
      hospital mortality and to calculate risk-adjusted mortality rates. RESULTS: For
      AVR, the trend in patient casemix was toward increased risk with increases in
      patient age and in the proportion of patients with: body surface area less than
      1.7, diabetes, coronary artery disease, and prior valve surgery. A decrease was
      noted in the proportion of patients undergoing additional surgical procedures.
      For MVR, patient risk improved over the time period with fewer female patients
      and fewer patients with coronary artery disease. For mitral valve repair patient
      risk increased over the time period with increases in the proportion of patients
      with coronary artery disease, diabetes, and whose surgical priority was
      classified as urgent. In addition, there was a borderline significant increase in
      the proportion of mitral valve repair patients in New York Heart Association
      class IV preoperatively. Risk-adjusted mortality decreased 44% from 9.3% in 1992
      through 1993 to 5.3% in 1996 through 1997 for patients undergoing AVR (p = 0.01)
      and decreased 53% from 13.6% in 1992 through 1993 to 8.2% in 1996 through 1997
      for patients undergoing MVR (p = 0.01). We observed a statistically insignificant
      increase in risk-adjusted mortality over the time period for patients undergoing
      mitral valve repair (from 3.6% in 1992 through 1993 to 5.0% in 1996 through 1997;
      p = 0.34). CONCLUSIONS: Significant improvement in mortality rates with valve
      replacement was observed in northern New England during this time period. This
      improvement persisted following adjustment for changes in patient casemix over
      this time. These trends mirror improvements in mortality with other cardiac
      surgical interventions that have been observed in recent years in our region and
      nationally.

PMID- 10969659
TI  - Cardiac valve replacement in patients on dialysis: influence of prosthesis on
      survival.
AB  - BACKGROUND: Mechanical valves have been recommended for patients on dialysis
      because of purported accelerated bioprosthesis degeneration. This study was
      undertaken to determine time-related outcomes in dialysis patients requiring
      cardiac valve replacement. METHODS: From 1986 to 1998, 42 patients on chronic
      preoperative dialysis underwent valve replacement; 17 received mechanical valves
      and 25 received bioprostheses. Age was similar in both groups: 54+/-18.5 years
      (mechanical) and 59+/-15.5 years (bioprosthetic, p = 0.4). Sites of valve
      replacement were aortic (27), mitral (11), and aortic and mitral (4). Follow-up
      was 100% complete. RESULTS: Survival at 3 and 5 years was 50% and 33% after
      mechanical valve replacement, and 36% and 27% after bioprosthetic valve
      replacement (p = 0.3). Four patients with bioprostheses required reoperation: 3
      for allograft endocarditis and 1 at 10 months for mitral bioprosthesis
      degeneration. One patient who received a mechanical valve required reoperation.
      CONCLUSIONS: Prosthetic valve-related complications in patients on dialysis were
      similar for both mechanical and bioprosthetic valves. Because of the limited life
      expectancy of patients on dialysis, bioprosthesis degeneration will be uncommon.
      Therefore, surgeons should not hesitate to implant bioprosthetic valves in these
      patients.

PMID- 10969660
TI  - Annular abscesses in surgical endocarditis: anatomic, clinical, and operative
      features.
AB  - BACKGROUND: The aim of this study was to determine patterns of anatomic,
      clinical, and operative features in surgical endocarditis (SE) with annular
      abscess (AA). METHODS: The study consisted of a retrospective analysis of SE
      cases with AA between 1981 and 1997. RESULTS: A total of 41 cases with AA were
      found in 106 consecutive SE cases. There was a higher incidence of AA in aortic
      (37 of 71 [52%]) (p<0.01) compared to mitral (6 of 42 [14.3%]) or tricuspid (0 of
      12) infections. However, the mitral abscesses had a greater tendency toward
      fistula or pseudoaneurysm formation (4 of 6 [67%]) than other valve abscess
      cavities (7 of 46 [15%]) (p<0.01). Severe heart failure (p<0.01), heart block
      (p<0.05), and fistula/pseudoaneurysm (p<0.001), were more often found in SE with
      AA than without. There were 46 separate aortic AA in 37 instances of aortic valve
      SE. Of these, 31 of 46 (67%) were less than 1 cm (group 1), 10 of 46 (22%) were
      large but confined to a given cusp annulus (group 2), 4 of 46 (8.6%) were large
      between multiple cusps (group 3), and 1 of 46 (2.2%) was circumferential (group
      4). There were four instances of aortoventricular discontinuity. Group 1
      abscesses were repaired by local closure without a patch significantly more often
      than the other groups. The mortality of SE with AA was significantly greater for
      larger AA (groups 3 and 4, 3 of 5 [60%]) than for smaller AA (groups 1 and 2, 0
      of 36) (p<0.001). There were six separate mitral AA in six instances of mitral
      SE, five requiring patch repair. The 30-day operative mortality for AA cases was
      3 of 41 (7.3%) compared to 2 of 65 (3.1%) without AA. All AA mortalities involved
      large AA in the aortic valve position. Of 35 mechanical valves placed for AA,
      only one required subsequent removal for prosthetic endocarditis. CONCLUSIONS:
      Annular abscesses are most frequent in aortic AA, but fistulas/pseudoaneurysms
      are more frequent in mitral AA. Small to moderate aortic AA can be managed by
      local closure without an increased mortality compared to SE without AA. Patients
      with large aortic AA have a higher operative mortality. Mechanical prostheses are
      safe and effective for the majority of patients with AA.

PMID- 10969661
TI  - Ten-year trends in heart valve replacement operations.
AB  - BACKGROUND: There has been increasing concern in recent years about the quality
      and cost of heart valvular replacement procedures. The purpose of this study is
      to examine the profile of patients undergoing valvular operations during the past
      decade, and to look at trends in outcome and resource utilization over that
      period. METHODS: Clinical and procedural data of 2,972 patients undergoing heart
      valve replacement at Emory University Hospitals between 1988 and 1997 were
      recorded prospectively on standardized forms by trained medical personnel and
      entered into a computerized database. RESULTS: There were 1,802 patients
      undergoing aortic valve replacement (AVR), 966 undergoing mitral valve
      replacement (MVR), and 204 undergoing combined aortic and mitral valve procedures
      (AVR + MVR). No patients were excluded. There was a statistically significant
      trend for patients undergoing AVR, MVR, or AVR + MVR over time to be older and
      sicker by multiple criteria. Nonetheless, procedural outcome and inhospital
      mortality for patients undergoing AVR remained unchanged. Cost and length of stay
      increased from 1988 to 1992 when a concerted effort to decrease resource
      utilization began. Between 1992 and 1997 for AVR, length of stay decreased from
      13.4 to 8.0 days and cost from $37,047 to $21,856. Similarly, between 1992 and
      1997 for MVR, length of stay decreased from 15.6 to 8.1 days and cost from
      $45,072 to $21,747. The net result over the time period from 1988 to 1997 was an
      average decline in the cost of operation of $785 a year, adjusted for other
      factors. CONCLUSIONS: This study reveals that outcome of valvular replacement
      during the period from 1988 to 1997 has remained constant despite the patients
      becoming older and sicker during the same period. This constant outcome has been
      accomplished, but length of stay has decreased significantly. Hospital costs
      increased during the first years of the study period, but then decreased to
      levels in 1997 that were equal to or significantly less than 1988 levels.

PMID- 10969662
TI  - Minimally invasive direct coronary artery bypass grafting: midterm results and
      quality of life.
AB  - BACKGROUND: There is increasing interest in minimally invasive direct coronary
      artery bypass grafting (MID-CABG); however, there is still little information
      about midterm results and postoperative quality of life. METHODS: From March 1995
      to March 1998, 64 patients underwent MIDCABG at our hospital. Their mean age was
      60+/-9.5 years; 22 (34.4%) had unstable angina. All patients were followed-up by
      both direct visit and questionnaire to assess the postoperative quality of life.
      RESULTS: There were no perioperative deaths nor conversions to sternotomy; the
      perioperative myocardial infarction rate was 1/64 (1.6%). Predischarge
      angiography showed overall and unobstructed patency rates of 96.8% (62 of 64) and
      93.8% (60 of 64), respectively. At follow-up (25+/-11.4 months) actuarial
      survival was 100%, and survival free of myocardial infarction was 98.4%+/-1.6% at
      3 years. Both the Physical Activity Score and the Psychological General Well
      being Index improved significantly after the operation, with percentage
      improvements of 31% and 23%, respectively, at 12 months postoperatively.
      CONCLUSIONS: In selected patients MIDCABG can be a reliable and safe option.
      Patients who undergo this procedure are free of major complications and enjoy a
      good quality of life after surgery.

PMID- 10969663
TI  - Effects of minimal invasive coronary artery bypass on pulmonary function and
      postoperative pain.
AB  - BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) requires
      substantially smaller incisions than conventional coronary artery bypass grafting
      (CABG). We investigated whether this fact may lead to less postoperative pain and
      improved pulmonary function. METHODS: Preoperative and postoperative (days 1, 3,
      and 5) pulmonary function and postoperative pain were assessed in 15 patients
      undergoing MIDCAB (group A) by using a standardized score and were compared with
      15 patients admitted for CABG (group B). RESULTS: Total operation time (140
      minutes versus 189 minutes; p<0.001) and duration of mechanical ventilation (300
      minutes versus 840 minutes; p<0.001) were significantly less in group A.
      Pulmonary function was comparable between the 2 groups on postoperative day 1
      (POD 1). Vital capacity was significantly greater in group A on POD 3 (59.7%
      versus 40.6%; p<0.001) and on POD 5 (74.4% versus 53.9%; p<0.001). Similar
      results were found for forced expiratory volume in 1 second (group A versus B on
      POD 3: 56.3% versus 42.2%; p<0.05; and on POD 5: 68.4% versus 55.5%; p<0.01).
      Postoperative pain was significantly higher in group A (POD 1: score 5.5 versus
      3.6; POD 3: 4.0 versus 2.9; p<0.01). CONCLUSIONS: MIDCAB procedures lead to
      better preservation of pulmonary function compared with conventional CABG despite
      greater postoperative pain.

PMID- 10969664
TI  - Heart displacement during off-pump CABG: how well is it tolerated?
AB  - BACKGROUND: Heart displacement during off-pump coronary artery bypass grafting
      (CABG) is necessary to expose the anastomosic sites. We analyzed the hemodynamic
      changes in relation to the grafted arteries. METHODS: The relationship between
      surgical exposure and hemodynamic management was assessed in 150 consecutive
      patients undergoing off-pump CABG utilizing the Octopus Tissue Stabilization
      System (Medtronic, Minneapolis, MN). RESULTS: Surgical exposure by anterolateral
      thoracotomy showed no significant hemodynamic changes. Through sternotomy, stroke
      volume was significantly reduced by dislocation at all target sites: by 6% at the
      left anterior descending artery (LAD), 25% at the diagonal branch artery (D), 14%
      at the right coronary artery (RCA), and 21% at the obtuse marginal artery (OM).
      The application of head-down positioning (LAD, 56%; D, 74%; RCA, 90%; OM, 96%)
      increased not only surgical exposure but also preload, producing correction of
      ventricular filling pressures and output. In a minority of cases, dopamine (3 to
      5 microg x kg(-1) x min(-1)) was added to maintain baseline hemodynamic values
      (LAD, 5%; D, 15%; RCA, 7%; OM, 28%). CONCLUSIONS: Revascularization during
      anterolateral thoracotomy was uneventful. The sternotomy approach with heart
      displacement induced right heart compression. Mainly fluid redistribution was
      sufficient to correct cardiac output. Once stabilized, systemic circulation
      remained unchanged during revascularization.

PMID- 10969665
TI  - Minimally invasive saphenous vein harvesting techniques: morphology and
      postoperative outcome.
AB  - BACKGROUND: Conventional saphenous vein harvest is associated with numerous
      complications, which may be reduced by minimally invasive vein-harvesting
      techniques. The integrity of the venous endothelium must be guaranteed before
      using new saphenous vein harvesting techniques. This short-term study compared
      the clinical outcome of two minimally invasive techniques with the conventional
      technique, and compared morphology as documented by light and electron
      microscopy. METHODS: Ninety-two patients were prospectively randomized into three
      groups. Two different minimally invasive techniques of greater saphenous vein
      harvesting were used in sixty-two patients. One used a video-assisted dissector
      (group A, n = 31), and one used a light-coupled retractor (group B, n = 31).
      Thirty patients were treated by the conventional technique (group C). RESULTS:
      Incision lengths were 7.6+/-2.1 cm in group A and 9.3+/-3.2 cm in group B, as
      compared with 38.9+/-8.7 cm in the conventional group. Harvesting time was
      prolonged by a mean of 26% when using a minimally invasive technique. Conversion
      rate to the open technique was 3 of 31 (9.3%) in group A and 2 of 31 (6.2%) in
      group B. No wound complications were noted in group A, but one wound inflammation
      was seen in group B; only a mild hematoma was seen in both groups. Edge necrosis,
      wound separation and inflammation were noted in the conventional group. Light and
      electron microscopy revealed no significant denudation of the endothelial layer
      in groups A and B as compared with group C. CONCLUSIONS: These data show an
      excellent postoperative result when using the minimally invasive technique as
      compared with the conventional group. The safety of the technique is demonstrated
      by the preservation of endothelial integrity.

PMID- 10969666
TI  - Survey of resident training in beating heart operations.
AB  - BACKGROUND: "Off-pump" coronary artery operations are done with increasing
      frequency in the treatment of coronary artery disease. As a result, residents in
      thoracic surgery have been confronted with the necessity of gaining experience in
      this innovative approach to coronary surgery. The aim of this study was to assess
      the importance of training in minimally invasive coronary revascularization as it
      was perceived by thoracic surgery residents. METHODS: A postal, multiple-choice
      survey questionnaire was sent to all cardiothoracic surgery residents (n = 327)
      of accredited training programs in the United States. Responses were tabulated
      and analyzed. RESULTS: The overall response rate was 68% (222 of 327 residents).
      The attending staff was very interested (37%), or had some interest (63%), in
      beating heart coronary revascularization. Ninety-eight percent of the programs
      had at least one surgeon performing off-pump procedures. Although 88% of the
      responding residents showed some interest in off-pump coronary operations, only
      22% of them had performed more than 20 off-pump cases, and even less (12%) had
      performed more than 20 cases of off-pump complete revascularization, or off-pump
      circumflex revascularization (4%). Sixteen percent of them had no clinical
      experience with these techniques. Regarding career intentions, 88% of the
      residents indicated that off-pump coronary operations were expected to be part of
      the practice, and 58% of them were interested in pursuing additional training in
      less invasive heart procedures. CONCLUSIONS: The results of this survey suggest
      that training in off-pump coronary revascularization is variable across training
      programs, and that the majority of residents may not reach proficiency in
      coronary procedures on the beating heart during their residency. This may
      adversely affect their future expectations, as 88% of them would like to practice
      off-pump coronary surgery once the training is completed.

PMID- 10969667
TI  - Third-time coronary artery bypass grafting.
AB  - BACKGROUND: In this study we analyze the short- and long-term results, and the
      clinical, functional, and subjective status of patients after a second coronary
      reoperation (RE-RE-CABG). METHODS: The perioperative data of 33 consecutive
      patients undergoing RE-RE-CABG (1987 to 1998) were studied. Follow-up information
      was obtained from our follow-up databank. A cross-sectional follow-up was
      conducted, with additional functional evaluation by the Duke Activity Status
      Index (DASI), and patients' evaluations of their life situation were registered.
      RESULTS: Perioperative mortality was 2 of 33 patients (6%). During the follow-up
      (mean 51.6 months) 5 patients died. The 26 survivors showed a significant
      decrease in New York Heart Association class from 3.6+/-0.4 preoperatively versus
      2.2+/-0.6 postoperatively. The mean Duke Activity Status Index score was 29.30+/
      16.34 (range 7.22 to 48.9). In all, 18 of 26 patients (70%) were declared to have
      benefitted from the RE-RECABG. CONCLUSIONS: The significant improve in New York
      Heart Association class and good postoperative functional capacity, justified the
      RE-RE-CABG. However, patients must be informed about the limitations of this
      procedure.

PMID- 10969668
TI  - Histologic evidence of the safety of endoscopic saphenous vein graft preparation.
AB  - BACKGROUND: Endoscopic methods of saphenous vein procurement have recently been
      introduced. These techniques have been successful in limiting pain and wound
      complications, but less information on assessing potential trauma to the
      harvested vein segment is available. METHODS: Fourteen male patients undergoing
      coronary artery bypass grafting were included in the study. Nine patients
      underwent endoscopic procurement of saphenous vein whereas 5 patients underwent
      procurement using standard open techniques. Histologic appearance and
      immunohistochemical studies (factor VIII:vWF [von Willebrand factor protein] and
      CD34) of the vein segments were reviewed in a blinded fashion. RESULTS: On
      histologic analysis, no differences in the intima, media, or adventitia were
      found between endoscopically and conventionally obtained vein segments.
      Immunohistochemical staining for factor VIII:vWF and CD34 showed no differences
      between veins harvested by the two techniques. CONCLUSIONS: Endoscopic saphenous
      vein harvesting does not appear to traumatize the vessel wall any more than open
      techniques. Longitudinal assessment is necessary to evaluate long-term patency in
      vein grafts procured using this method.

PMID- 10969669
TI  - Major leg wound complications after saphenous vein harvest for coronary
      revascularization.
AB  - BACKGROUND: Major leg wound complications after coronary artery bypass graft
      procedures are infrequent and few are reported in the literature. We present our
      experience in treating 23 patients with major leg wound complications after
      coronary revascularization procedures. METHODS: A retrospective review of 3,525
      bypass procedures with saphenous vein grafts performed over a 10-year period was
      conducted. Ten potential risk factors for those who developed major leg wound
      complications were analyzed and compared with the entire cohort of patients
      undergoing similar bypass procedures during the same period. RESULTS: Lower
      extremity wound complications occurred in 145 patients (4.1%), 23 of whom (0.65%)
      required additional surgical interventions (62 total). There were 32 wound
      debridements, 8 skin grafts, 11 vascular procedures, 5 amputations, 3
      fasciotomies, 2 free tissue transfers, and 1 fasciocutaneous flap. Of ten
      variables evaluated by multivariate analysis, female gender, peripheral vascular
      disease, and postoperative intraaortic balloon pump use were identified as
      significant independent predictors of major leg wound complications (p < 0.0001).
      CONCLUSIONS: The causes of major leg wound complications after saphenous vein
      harvest for coronary artery bypass graft procedures are multifactorial. To
      minimize these complications, we recommend vascular evaluations before saphenous
      vein harvest, attention to proper surgical technique, and careful harvest site
      selection.

PMID- 10969670
TI  - Transmyocardial laser revascularization with excimer laser: clinical results at 1
      year.
AB  - BACKGROUND: Transmyocardial laser revascularization, a new strategy for the
      treatment of diffuse ischemic heart disease, uses laser technology for the
      theoretical purpose of forming transmyocardial channels in the heart to increase
      perfusion to ischemic zones. This report summarizes our initial clinical
      experience with the procedure. METHODS: Excimer transmyocardial laser
      revascularization was performed in a reversibly ischemic region of the heart in
      15 patients. Ischemia and myocardial viability were evaluated by assessment of
      symptoms and of results of radionuclide single photon emission computed
      tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring.
      RESULTS: No adverse events occurred as a result of the laser revascularization,
      although 1 patient with preoperative ventricular arrhythmias died 48 hours
      postoperatively as a result of refractory ventricular tachycardia. Angina class
      decreased significantly from base line values in patients who had undergone the
      procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at
      base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months,
      1.8+/-0.8 at 12 months; p<0.002), and nitroglycerin requirements were similarly
      decreased in patients who had undergone laser revascularization (mean g/wk of
      sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3
      months, 4+/-2 at 6 months, 2+/-1 at 12 months; p<0.02). Exercise tolerance
      testing demonstrated increase in exercise duration compared with base line values
      (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3
      months, and 9.0+/-3.9 at 12 months; p>0.05); those increases were not large
      enough to be statistically significant, however. CONCLUSIONS: Our data are
      consistent with the concept that excimer transmyocardial laser revascularization
      in individuals with significant ischemic heart disease appears to be well
      tolerated, can be performed safely, and may lead to a reduction in ischemic
      symptomatology.

PMID- 10969671
TI  - Induction of angiogenesis after TMR: a comparison of holmium: YAG, CO2, and
      excimer lasers.
AB  - BACKGROUND: Transmyocardial laser revascularization (TMR) is an emerging
      treatment for end-stage coronary artery disease. A variety of lasers are
      currently available to perform the procedure, although their relative efficacy is
      unknown. The purpose of this study was to compare changes in myocardial blood
      flow and function 6 months after TMR with holmium:yttrium-aluminum-garnet
      (holmium:YAG), carbon dioxide (CO2), and xenon chloride excimer lasers in a model
      of chronic ischemia. METHODS: Miniswine underwent subtotal (90%) left circumflex
      coronary stenosis. Baseline positron emission tomography and dobutamine stress
      echocardiography were performed to document hibernating myocardium in the left
      circumflex coronary artery distribution. Animals were then randomized to sham
      redo-thoracotomy (n = 5) or TMR using a holmium:YAG (n = 5), CO2 (n = 5) or
      excimer (n = 5) laser. Six months postoperatively, the positron emission
      tomography and dobutamine stress echocardiography studies were repeated and the
      animals sacrificed. RESULTS: In animals undergoing TMR with holmium: YAG and CO2
      lasers, a significant improvement in myocardial blood flow to the lased left
      circumflex regions was seen. No significant change in myocardial blood flow was
      seen in sham- or excimer-lased animals. There was a significant improvement in
      regional stress function of the lased segments 6 months postoperatively in
      animals undergoing holmium:YAG and CO2 laser TMR that was consistent with a
      reduction in ischemia. There was no change in wall motion in sham- or excimer
      lased animals. Significantly greater neovascularization was observed in the
      holmium:YAG and CO2 lased regions than with either the sham procedure or excimer
      TMR. CONCLUSIONS: Transmyocardial laser revascularization with either holmium:YAG
      or CO2 laser improves myocardial blood flow and contractile reserve in lased
      regions 6 months postoperatively. These changes were not seen following excimer
      TMR or sham thoracotomy, suggesting that differences in laser energy or
      wavelength or both may be important in the induction of angiogenesis.

PMID- 10969672
TI  - Economic impact of preoperative intraaortic balloon pump therapy in high-risk
      coronary patients.
AB  - BACKGROUND: The efficacy of preoperative intraaortic balloon pump therapy in high
      risk coronary patients has been demonstrated earlier. METHODS: This study
      investigates the economic aspect by a detailed cost analysis of pooled
      information from two previously published randomized studies and 144 consecutive
      low-risk coronary artery bypass graft operations. Costs for patients receiving
      preoperative intraaortic balloon pump therapy before aortic cross-clamping (n =
      62) were compared to those in a control group (n = 50). Detailed cost analysis
      was based on data provided by the hospital finance department. RESULTS: The total
      hospital costs were as follows: low-risk coronary artery bypass graft operations
      cost 35,335+/-1,694 Swiss francs ($23,400+/-$1,121); high-risk coronary artery
      bypass graft without preoperative intraaortic balloon pump therapy cost 65,892+/
      31,719 Swiss francs ($43,637+/-$21,006); and high risk coronary artery bypass
      graft with preoperative intraaortic balloon pump therapy cost 41,948+/-10,379
      Swiss francs ($27,780+/-$6,874) (p = 0.0015). There were no significant
      differences in average cost among the preoperative intraaortic balloon pump
      therapy subgroups. CONCLUSIONS: Preoperative intraaortic balloon pump therapy in
      high risk coronary patients is significantly cost-beneficial, With an average
      saving of 24,000 Swiss francs ($16,000) on the total hospital cost, a 36% cost
      reduction.

PMID- 10969673
TI  - Abciximab and bleeding during coronary surgery: results from the EPILOG and
      EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.
      Evaluation of Platelet IIb/IIIa Inhibition in STENTing.
AB  - BACKGROUND: Abciximab during percutaneous coronary revascularization reduces
      ischemic complications, but concern exists regarding increased bleeding risk
      should emergency coronary surgical procedures be required. METHODS: Outcomes were
      assessed among 85 patients who required coronary artery bypass grafting
      operations after coronary intervention in two randomized placebo-controlled
      trials of abciximab. Comparisons were made between patients in the pooled placebo
      and abciximab groups. RESULTS: The incidence of coronary surgical procedures was
      2.17% and 1.28% among patients randomized to placebo and abciximab, respectively
      (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients
      in the placebo and abciximab groups, respectively (p = 0.059). Rates of major
      blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p
      = 0.27); transfusions of packed red blood cells or whole blood were administered
      in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for
      bleeding was required in 3% and 12% of patients, respectively. Death and
      myocardial infarction tended to occur less frequently among patients who had
      received abciximab. CONCLUSIONS: Urgent coronary artery bypass grafting
      operations can be performed without an incremental increase in major hemorrhagic
      risk among patients on abciximab therapy.

PMID- 10969674
TI  - Intramyocardial impedance measurements for diagnosis of acute cardiac allograft
      rejection.
AB  - BACKGROUND: Measurements of intramyocardial impedance at high frequencies can
      indicate alterations in cell membranes and intracellular spaces during acute
      cardiac allograft rejection. METHODS: Fifteen beagle dogs underwent heterotopic
      heart transplantation and were immunosuppressed with cyclosporine and methyl
      prednisolone (MP). Impedance was determined twice daily by means of four screw-in
      electrodes in the right and left ventricle. Transmyocardial biopsies and the
      intramyocardial electrogram (IMEG) were performed as reference methods. A total
      of 23 rejection episodes were induced. When acute rejection was recognized
      histologically and through IMEG readings, the animals were treated with a bolus
      of 125 mg of methyl prednisolone over 5 consecutive days. Treatment of rejection
      was controlled by biopsy and IMEG. RESULTS: All hearts showed a uniform decrease
      in impedance of about 28.3%+/-5.5% immediately after transplantation, which
      subsequently reached a stable plateau after 7 to 8 days. Impedance values then
      remained unchanged as long as rejection was absent. Biopsy findings of grades 1A
      to 1B (ISHLT) were accompanied by a statistically significant increase in
      impedance of 12.2%+/-2.5%; of grades 2 to 3A of 19.2%+/-3.2% and of grades 3B to
      4 of 27.0%+/-2.9%. Sensitivity was 96%, specificity 91%. Successful treatment of
      rejection led to a decrease of impedance to the initial levels. CONCLUSIONS: The
      amount of increase in impedance of high frequencies is a method to stratify acute
      cardiac allograft rejection into grades like histologically grading. The
      effectiveness of rejection treatment can also be monitored through impedance
      measurement. The method is also applicable for telemetric rejection monitoring by
      means of an implantable device.

PMID- 10969675
TI  - Alterations in coagulation after implantation of a pulsatile Novacor LVAD and the
      axial flow MicroMed DeBakey LVAD.
AB  - BACKGROUND: The MicroMed DeBakey left ventricular assist device (LVAD) is a
      chamber and valveless axial flow blood pump. We investigated parameters of the
      coagulation system in patients after implantation of the axial flow LVAD and
      patients following implantation of a pulsatile Novacor LVAD. METHODS: Six
      consecutive patients of both groups were investigated over a period of 6 weeks
      after implantation. beta-Thromboglobulin, platelet factor 4, factor XIIa,
      thrombin/antithrombin complexes, plasmin/alpha2-antiplasmin complexes, and D
      Dimer levels were measured. RESULTS: With the exception of the plasmin/alpha2
      antiplasmin levels in the Novacor group, all parameters were elevated in both
      groups. The levels of beta-thromboglobulin, platelet factor 4, factor XIIa, and
      plasmin/alpha2-antiplasmin were significantly increased in the axial flow LVAD
      group. CONCLUSIONS: The axial flow LVAD strongly influences the systems of
      contact activation and fibrinolysis. The elevation of platelet proteins appears
      to follow platelet damage. Although no thromboembolic events were observed in
      both groups, elevation of thrombin/antithrombin complexes provides convincing
      evidence of an increased activation of the coagulation system and the concomitant
      risk for the development of thromboembolism.

PMID- 10969676
TI  - Wound complications after left ventricular assist device implantation.
AB  - BACKGROUND: Wound necrosis and infection pose a tremendous risk for patients with
      left ventricular assist devices. METHODS: We analyzed our database of patients
      with left ventricular assist devices for those who developed wound dehiscence and
      concomitant infection after left ventricular assist device implantation. RESULTS:
      Three of our 66 patients (4.5%) with implantable ventricular assist devices had
      had severe wound complications with necrosis of the abdominal or thoracic wall
      uncovering part of the device. The predominant impact on the development of these
      complications was presumably related to multiple surgical interventions on the
      same site. CONCLUSIONS: Nevertheless, these patients can recover and undergo
      successful heart transplantation if adequately managed.

PMID- 10969677
TI  - Remodeling of the aortic root and reconstruction of the bicuspid aortic valve.
AB  - BACKGROUND: Currently, isolated reconstruction of a regurgitant bicuspid aortic
      valve can be performed with adequate early results. Dilatation of the proximal
      aorta is known to be associated with this valve anomaly and may be partially
      responsible for the development of primary regurgitation or secondary failure of
      valve repair. We have used repair of the bicuspid valve with remodeling of the
      aortic root as an alternative to insertion of a composite graft. METHODS: Between
      October 1995 and May 1999, 16 patients (12 men, 4 women, aged 35 to 73 years)
      were seen with a regurgitant bicuspid aortic valve and dilatation of the proximal
      aorta of more than 50 mm. All patients underwent repair of the valve using either
      coapting sutures alone (n = 12) or in combination with triangular resection of a
      median raphe (n = 4). Using a Dacron graft, the aortic root was remodeled and the
      ascending aorta (n = 16) and proximal arch (n = 4) replaced. RESULTS: No patient
      died. The postoperative degree of aortic regurgitation was less than grade II in
      all patients. Valve function has remained stable in all patients between 2 and 43
      months postoperatively. CONCLUSIONS: Reconstruction of the regurgitant bicuspid
      valve in the presence of proximal aortic dilatation is feasible with good results
      by combining the root remodeling technique with valve repair.

PMID- 10969678
TI  - Mediastinal false aneurysm after thoracic aortic surgery.
AB  - BACKGROUND: Postoperative mediastinal false aneurysm is associated with a
      substantial morbidity and mortality. Surgical treatment is mandatory, although
      the individual approach varies according to the type of pathologic process,
      infection status, and site of origin of the aneurysm. METHODS: Between April 1993
      and February 1999, we treated 10 patients, aged 25 to 73 years, with anastomotic
      mediastinal false aneurysm originating from the proximal thoracic aorta. Nine had
      undergone prior operations on the ascending aorta (7, type A dissection repair;
      1, aortitis; 1, root abscess) with a Dacron conduit (n = 5) or valved conduit (n
      = 4). The last patient had undergone valve replacement for excavating aortic root
      sepsis. False aneurysms were detected from 2 to 70 months after the most recent
      operation. Three patients had positive tissue cultures. The surgical procedure
      was direct suture repair of the disrupted anastomosis in 5, root or ascending
      aortic replacement with an aortic homograft in 4, and Dacron graft interposition
      in 1. Hypothermic low-flow perfusion with or without circulatory arrest was used
      in all patients. RESULTS: There was one hospital death caused by staphylococcal
      mediastinitis. A false aneurysm recurred after direct suture repair in 2 patients
      with underlying type A dissection or aortitis. This resulted in one late death.
      One patient experienced a neurologic event during removal of an infected vascular
      graft. All 8 surviving patients are alive and well after a mean follow-up of 2
      years. Three patients with mycotic false aneurysms remain free from infection
      after aortic homograft replacement. CONCLUSIONS: Mediastinal false aneurysms are
      surgically taxing. Low-flow hypothermic perfusion with or without circulatory
      arrest allows safe reentry. Radical surgery provides a satisfactory outcome in
      infected patients. Local repair of suture dehiscence in pathologic tissues may
      predispose to recurrence. We suspect that excessive use of formalin in gelatin
      resorcin-formol glue may predispose to tissue necrosis.

PMID- 10969679
TI  - Surgical treatment of acquired left ventricular pseudoaneurysms.
AB  - BACKGROUND: We present a review of our experience with acquired pseudoaneurysms
      of the left ventricle in order to establish the risk of surgical repair. METHODS:
      Ten patients operated upon for a left ventricular pseudoaneurysm in our clinic
      between 1984 and 1999 were reviewed. The pseudoaneurysm, a complication of
      myocardial infarction (four acute and three chronic) or previous cardiac surgery
      (three chronic), was resected in all patients and the ventricular wall defect
      closed with direct sutures (five cases) or a patch (five cases). Coronary artery
      bypass graft was performed in 6 patients. RESULTS: Three patients died
      (postoperative mortality 30%) after repair of an acute postinfarction (2
      patients) or a chronic postsurgical (1 patient) pseudoaneurysm. Three patients
      died during follow-up (median 4 years) of a carcinological (2 patients) or
      cardiac (1 patient) cause. Two years after repair, 5 patients were in New York
      Heart Association class I or II, and 1 patient was in class III. CONCLUSIONS:
      Repair of left ventricular pseudoaneurysms can be performed with acceptable
      results, although mortality is significant in acute myocardial infarction and
      redo operations. Propensity for fatal rupture, however, is higher than the
      surgical risk in acute pseudoaneurysms or in large or expanding chronic ones and
      warrants surgical repair. The best approach to small asymptomatic chronic
      pseudoaneurysm is unsettled.

PMID- 10969680
TI  - Complications associated with clamping the aorta between the left common carotid
      artery and left subclavian artery.
AB  - BACKGROUND: Hypothermic circulatory arrest using a left thoracotomy has recently
      been recommended for repair of distal arch lesions to prevent the atheroembolism
      that often results from clamp injury. The recommendation holds even for cases in
      which aortic cross-clamping between the left common carotid artery and left
      subclavian artery is possible. METHODS: Over the last 16 years, 69 patients
      underwent repair of the distal arch or descending thoracic aorta using distal
      perfusion with the proximal aortic clamp placed between the left common carotid
      and left subclavian artery. The average age of the patients was 61+/-12 years; 18
      of them (26%) were older than 70 years. Forty-four patients (64%) had
      atherosclerotic true aneurysms. RESULTS: The surgical procedures used included
      patch closure of saccular aneurysms in 20 patients (29%) and graft replacement in
      47 (71%). The left subclavian artery was reattached in 7 patients (10%). Although
      there were 3 hospital deaths (4%), no cerebral complications occurred aside from
      temporary neurologic dysfunction in 4 patients (6%). CONCLUSIONS: An acceptably
      low incidence of cerebral complications is associated with cross-clamping the
      aorta between the left common carotid artery and left subclavian artery.

PMID- 10969681
TI  - Gene expression of inflammatory mediators in different chambers of the human
      heart.
AB  - BACKGROUND: Inflammatory genes may be unevenly expressed in different heart
      chambers. METHODS: Biopsies were taken simultaneously from the right atrium (RA),
      left atrium (LA), and left ventricle (LV) of 19 patients before cardioplegic
      arrest during open heart surgery. The mRNA expression of tumor necrosis factor
      alpha (TNFalpha), interleukin 1beta (IL-1beta), inducible and endothelial nitric
      oxide synthase (iNOS and eNOS), endothelin-1 (ET-1), E-selectin (CD62E),
      intercellular adhesion molecule-1 (ICAM-1) and its ligand CD18, and CD25 was
      evaluated with semiquantitative reverse transcription-polymerase chain reaction
      (RT-PCR). RESULTS: Expression of TNFalpha mRNA was higher in RA than LA and LV
      (p<0.05), whereas IL-1beta was more expressed in LA than RA (p<0.05), which was
      higher than LV (p<0.0001). There were no significant regional differences in the
      expression of ICAM-1, CD62E, CD25, iNOS, and eNOS. CD18 was higher in RA than LA
      (p<0.05); ET-1 was more expressed in RA than LV (p<0.04). Patients with stable
      angina had no expression of eNOS. CONCLUSIONS: Gene expression of inflammatory
      mediators was detected in the hearts of patients with different cardiovascular
      disorders, and was unevenly distributed in different heart chambers. Cardiac
      biopsies should be taken from the same site.

PMID- 10969683
TI  - Neurological evaluation and intelligence testing in the child with operated
      congenital heart disease.
AB  - BACKGROUND: The immediate and intermediate-term neurodevelopmental outcome in
      infants undergoing open heart procedures using deep hypothermic cardiopulmonary
      bypass was assessed prospectively. METHODS: One hundred consecutive infants (age
      2 to 174 days) were operated on using either deep hypothermic bypass only (group
      A, n = 28), or with associated circulatory arrest (group B, n = 72). Early
      neurological outcome was recorded. Survivors underwent mental development
      evaluation after 31 to 55 months. Fifty other children of similar demographic
      profile but without heart disease were also tested as controls. RESULTS: In group
      A, there were two neurological deaths. In group B, 5 patients had clinical
      seizures, 1 had monoparesis and 1 had hyperkinetic syndrome with decreased
      attention span. Mean mental performance quotient was 90.0+/-8.2 in group A, and
      89.1+/-6.8 in group B, (group A vs. B, p = 0.60). Mean mental performance
      quotient in the control group was 101.4+/-8.4, which was significantly higher
      than the patient population (p << 0.001). No correlation was found between
      duration of circulatory arrest and postoperative mental performance quotient.
      CONCLUSIONS: There was significant retardation of mental development in infants
      operated with deep hypothermic cardiopulmonary bypass. However, use of total
      circulatory arrest and its duration did not affect clinical outcome up to
      preschool age.

PMID- 10969682
TI  - Interventions associated with minimal fontan mortality.
AB  - BACKGROUND: The operative mortality rate for the first 400 Fontan procedures at
      this institution was 15% but declined to 4% for the next 100 procedures. METHODS:
      The cases of 100 consecutive patients receiving the Fontan procedure and
      associated with this change in mortality rate were reviewed to determine
      associations. RESULTS: The mortality rate in the first and second 50 patients was
      16% and 0%, respectively. There were no differences in age, number of risk
      factors, diagnosis, or operating surgeon between the two groups. Patients in the
      lower-mortality era were significantly more likely to have had a cavopulmonary
      anastomosis before a Fontan procedure (90% versus 70%) and to have an
      extracardiac Fontan procedure (38% versus 8%), shorter cross-clamp (45+/-24
      minutes versus 58+/-22 minutes) and cardiopulmonary bypass times (121+/-42
      minutes versus 141+/-45 minutes), magnesium-rich cardioplegia (100% versus 39%),
      hemoconcentration after bypass (67% versus 4%), and institution of pharmacologic
      support in the operating room. CONCLUSIONS: Patient characteristics and risk
      factors were similar in the two groups. However, several interventions that were
      increasingly utilized in the lower-mortality era, including the extracardiac
      Fontan procedure and modified ultrafiltration after bypass, are associated with
      lower mortality. Each one had the potential to improve postoperative myocardial
      function.

PMID- 10969684
TI  - Neutrophil degranulation and complement activation during fetal cardiac bypass.
AB  - BACKGROUND: Fetal cardiac bypass results in dysfunction of the fetoplacental unit
      (FPU) characterized by increased placental vascular resistance and respiratory
      acidosis. However the mechanisms of this dysfunction are not completely
      understood. To test the hypothesis that complement activation and neutrophil
      degranulation may contribute to the placental dysfunction associated with fetal
      bypass, we compared placental hemodynamics, complement activation, and neutrophil
      degranulation among fetuses exposed to cardiac bypass with a miniaturized bypass
      circuit including an in-line axial flow pump (Hemopump), fetuses undergoing
      bypass with a conventional roller pump circuit, and control fetuses that were
      similarly exposed but did not undergo bypass. METHODS: Twenty-six Western Cross
      sheep fetuses (median 122 days gestation) were randomly assigned to undergo
      cardiac bypass for 30 minutes with the Hemopump circuit (n = 8), to undergo
      bypass for 30 minutes with the conventional (roller pump) circuit (n = 10), or to
      undergo identical exposure and cannulation but not bypass (n = 8, controls).
      Blood samples were collected to measure white cell count and differential, and
      C3a and lactoferrin levels prior to bypass, at the end of bypass, and 1 and 2
      hours after bypass. Hemodynamics and blood gases were also monitored. RESULTS:
      There was a fall in white cell count over time that continued after bypass in all
      groups; neutrophils and lymphocytes were affected similarly. C3a levels rose
      significantly from prebypass to postbypass in the roller pump group (p<0.0001)
      but not in either of the other groups. Lactoferrin levels rose significantly from
      start of bypass in both bypass groups (Hemopump p = 0.01; roller pump p<0.0001)
      but not in controls. The elevation in lactoferrin level coincided with worsening
      placental gas exchange and deteriorating cardiac function. CONCLUSIONS:
      Complement and neutrophil activation occurred with fetal cardiac bypass but only
      neutrophil activation mirrored the FPU and cardiac dysfunction, suggesting that
      products of neutrophil activation may be important contributing factors. Improved
      FPU function with a bypass circuit that has less extracorporeal surface and does
      not require a large priming volume may be due in part to a reduction in the
      magnitude of this inflammatory response.

PMID- 10969685
TI  - Is adenosine preconditioning truly cardioprotective in coronary artery bypass
      surgery?
AB  - BACKGROUND: The large number of experimental studies showing that adenosine
      "turns on" the protein kinase C (PKC)-mediated pathway that accounts for the
      cardioprotection conferred by ischemic preconditioning contrasts with the
      scarcity of clinical data documenting the preconditioning-like protective effect
      of adenosine during cardiac operations on humans. METHODS: Forty-five patients
      undergoing coronary artery bypass were randomized to receive, after the onset of
      cardiopulmonary bypass, a 5-minute infusion of adenosine (140 microg x kg(-1) x
      min(-1)) followed by 10 minutes of washout before cardioplegic arrest (n = 23) or
      an equivalent period (15 minutes) of prearrest drug-free bypass (controls, n =
      22). Outcome measurements included troponin I release over the first 48
      postoperative hours and activity of ecto-5'-nucleotidase, an admitted reporter of
      PKC activation, as assessed on right atrial biopsies taken before bypass and at
      the end of the preconditioning protocol (or after 15 minutes of bypass in control
      patients). RESULTS: Aortic cross-clamping times were not different between the
      two groups. Likewise, prebypass values of ecto-5'-nucleotidase (nanomoles/mg
      protein per minute) were similar in control (3.14+/-1.02) and adenosine-treated
      (2.66+/-1.08) patients. They subsequently remained unchanged in control patients
      (3.87+/-1.65) whereas they significantly increased after adenosine
      preconditioning (4.47+/-1.96, p<0.001 versus base line values). However, peak
      postoperative values of troponin I (microg/L) were not significantly different
      between control (4.8+/-2.8) and adenosine-preconditioned patients (5.9+/-6.6) nor
      were the areas under the curve. There were no adverse effects related to
      adenosine. CONCLUSIONS: Adenosine, given at a clinically safe dose, can turn on
      the PKC-mediated signaling pathway involved in preconditioning but this
      biochemical event does not translate into reduced cell necrosis after coronary
      artery surgery, suggesting that a preconditioning-like protocol may not be the
      best suited for exploiting the otherwise well-documented cardioprotective effetcs
      of adenosine.

PMID- 10969686
TI  - Pharmacological preconditioning with the adenosine triphosphate-sensitive
      potassium channel opener pinacidil.
AB  - BACKGROUND: Ischemic preconditioning (IPC) decreases infarct size after global or
      regional ischemia. Potassium channel openers also precondition but are subject to
      dose-limiting vasodilation. We compared the mechanical and electrophysiological
      effects of ischemic and pharmacological preconditioning in an isolated rabbit
      heart model. METHODS: Rabbit hearts were preconditioned with either 10 micromol/L
      pinacidil alone (P-), 10 micromol/L pinacidil with 10 micromol/L phenylephrine
      (P+), or two cycles of global ischemia and reperfusion (IPC) before 1 hour of LAD
      occlusion. Left ventricular pressure, epicardial monophasic action potential
      duration (APD) and coronary flow were monitored throughout. Infarct size was
      determined at the end of reperfusion. RESULTS: Regional ischemia uniformly
      decreased APD (p<0.05). During reperfusion, APDs were prolonged beyond
      preischemic values in all preconditioned groups (p<0.05). P- and P+ reduced the
      incidence of fibrillation. P- significantly increased coronary flow (+15%, p =
      0.001), whereas IPC and P+ did not. However, IPC and P- significantly decreased
      systolic function (p<0.05) but P+ did not. In addition, IPC depressed diastolic
      function (p<0.05) but P- and P+ did not. Infarct size was reduced by all methods
      (p<0.05). CONCLUSIONS: Pinacidil presents a safe and effective alternative to IPC
      for preserving the heart during regional ischemia. Its coronary vasodilatory
      effects are safely and effectively reversed by the addition of phenylephrine.

PMID- 10969687
TI  - Preconditioning with PKC and the ATP-sensitive potassium channels: a codependent
      relationship.
AB  - BACKGROUND: Both potassium channel openers and protein kinase C have been shown
      to independently elicit the myoprotective preconditioning response. However, the
      in vivo dependency between the two is unknown. METHODS: Thirty-seven sheep were
      divided into seven groups; animals received no pretreatment, pinacidil, pinacidil
      and potassium channel opener blocker glibenclamide, protein kinase C activator
      4beta-phorbol-12,13-dibutyrate (PDBu), or PDBu and protein kinase C blocker
      chelerythrine. The last two groups underwent opposite blockade, chelerythrine +
      pinacidil, or glibenclamide + PDBu. All groups underwent 60 minutes of regional
      ischemia followed by 180 minutes of reperfusion. Regional function was assessed
      throughout the experiment, and at the conclusion of the study the infarct size
      (as a percentage of the area at risk) was determined. RESULTS: Infarct size
      decreased in the groups receiving only pinacidil or PDBu (control: 54%+/-3%,
      pinacidil: 25% +/-2%, PDBu: 21%+/-3%; p<0.05 pinacidil or PDBu versus control).
      This preconditioning protection was lost when the direct blocker was given (58%+/
      5%, glibenclamide + pinacidil; 70%+/-6%, chelerythrine + PDBu; p = not
      significant versus control). The preconditioning response was again attenuated
      when the opposite blockers were given (64%+/-5%, chelerythrine + pinacidil; 63%+/
      1%, glibenclamide + PDBu; p = not significant versus control). There was no
      significant difference in regional function. CONCLUSIONS: This study shows that
      both protein kinase C and potassium channels are necessary and codependent for
      preconditioning in the in vivo heart.

PMID- 10969688
TI  - Amrinone preconditioning in the isolated perfused rabbit heart.
AB  - BACKGROUND: Ischemic preconditioning (IPC) reduces infarct size in experimental
      preparations. IPC, however, is not without detrimental effects. We studied
      amrinone as a possible alternative to IPC. METHODS: Isolated perfused rabbit
      hearts were given a 5-minute infusion of 10 micromol/L amrinone followed by a 5
      minute washout (n = 6). The anterior descending artery was then occluded for 1
      hour and reperfused for 1 hour. Six hearts underwent IPC, with two episodes of 5
      minute global ischemia followed by 5-minute reperfusion before LAD occlusion;
      eight control hearts received no preconditioning. Left ventricular pressure and
      ischemic zone epicardial monophasic action potentials were continuously
      monitored. RESULTS: IPC but not amrinone reduced peak pressure before anterior
      descending artery occlusion. Peak pressure fell significantly during ischemia and
      reperfusion in all hearts. End diastolic pressure rose significantly during
      reperfusion in control and IPC hearts but not in amrinone hearts. Action
      potentials shortened during ischemia in all hearts. They returned to preocclusion
      values in control hearts but lasted beyond preocclusion values in IPC and
      amrinone hearts. Both the incidences of ventricular fibrillation and infarct size
      were significantly reduced in amrinone hearts but not in IPC hearts. CONCLUSIONS:
      Amrinone is not only a useful inotropic agent but is also a superior
      preconditioning agent when compared to IPC.

PMID- 10969690
TI  - Age dependence of heat stress mediated cardioprotection.
AB  - BACKGROUND: To study the influence of age on heat stress cardioprotection,
      functional recovery, nucleotide concentrations, and heat stress protein 70
      (Hsp70) levels were compared in the heat stressed (HS) and control (C) hearts at
      different ages, in a protocol mimicking donor heart preservation for
      transplantation. METHODS: Control and heat stressed (24 hours before experiment)
      rat hearts were divided into three age groups: (I) 1 month, (Y) 4 months, and (M)
      16 months (n = 6). Left ventricle balloon catheter was used to determine systolic
      and end-diastolic pressure/volume relations before and after 4 hours of
      cardioplegic arrest at 4 degrees C. Another identical set of isolated hearts
      underwent 5 minutes of normoxic perfusion to obtain preischemic Hsp70 content and
      metabolite concentrations. RESULTS: The postischemic recovery was highest in
      group HS-Y as compared to C-Y, HS-I, C-I, HS-M, and C-M. There were no
      differences in preischemic adenine nucleotides or creatine metabolite
      concentrations between the three age groups. In contrast, the nicotinamide
      adenine dinucleotide (oxidized form) (NAD+) and nicotinamide adenine dinucleotide
      phosphate (oxidized form) (NADP+) concentrations were significantly raised in
      group HS-Y. Hsp70 content was increased in all HS groups with no difference
      between the age groups. CONCLUSIONS: Improved postischemic functional recovery
      after cardioplegic arrest was observed in the young adult HS hearts. This was
      associated with highest NAD+ and NADP+ concentrations and did not correlate with
      increased Hsp70 content.

PMID- 10969689
TI  - The temperature dependence of cardioplegic distribution in the canine heart.
AB  - BACKGROUND: Cold cardioplegic arrest can produce cooling contracture and
      suboptimal myocardial protection. This study examines whether cooling contracture
      is associated with maldistribution of cardioplegic solution, particularly
      subendocardial hypoperfusion, which may impair recovery. METHODS: Canine hearts
      were arrested by antegrade cold and warm blood cardioplegia in random order.
      Cardioplegic distribution was measured using radiolabeled microspheres before and
      just after induction of each period of arrest. RESULTS: With cold cardioplegia,
      perfusion of left ventricular subepicardial and midwall regions decreased.
      Subendocardial to subepicardial perfusion ratios increased significantly in the
      left ventricle as a whole, the anterior and posterior regions of the left
      ventricular free wall, and the interventricular septum. With warm arrest,
      transmural flow distribution was not significantly altered from preceding
      prearrest values. At constant coronary flow, coronary perfusion pressure was
      initially similar after induction of arrest at both temperatures, but it rose
      subsequently during warm cardioplegia. CONCLUSIONS: The data suggest that during
      normothermic arrest, vasomotor tone regulates cardioplegic distribution, and
      hyperkalemic vasoconstriction is of slow onset. In the absence of beating and
      with vasomotion inhibited by hypothermia, cardioplegic distribution during cold
      arrest appears to be primarily dependent on vascular anatomy. There was no
      evidence of subendocardial underperfusion during cooling contracture.

PMID- 10969691
TI  - Effects of angiotensin-converting enzyme inhibitor during warm blood
      cardioplegia.
AB  - BACKGROUND: Effects of captopril, an angiotensin-converting enzyme inhibitor,
      during warm blood cardioplegia were assessed in the blood-perfused, isolated rat
      heart. METHODS: The isolated hearts were arrested for 60 minutes with warm blood
      cardioplegia given at 20-minute intervals and were reperfused for 60 minutes. The
      control group (n = 10) received standard cardioplegia and the captopril group (n
      = 10) received cardioplegia supplemented with captopril (2 mmol/L). Cardiac
      function, myocardial metabolism, and cardiac release of circulating adhesion
      molecules were assessed before and after cardioplegic arrest. RESULTS: Left
      ventricular end-diastolic pressure and -dp/dt were significantly (p<0.05) lower
      and coronary blood flow was significantly (p<0.05) greater in the captopril group
      than the control group during reperfusion. The captopril group resulted in
      significantly (p<0.05) less cardiac release of lactate, thiobarbituric acid
      reactive substances during reperfusion. Cardiac release of intercellular adhesion
      molecule-1 was significantly (p<0.05) less in the captopril group at 60 minutes
      of reperfusion. CONCLUSIONS: The results suggest that supplementation of
      captopril during warm blood cardioplegia provides superior myocardial protection
      by suppressing lipid peroxidation and leukocyte-endothelial cell interaction
      during reperfusion.

PMID- 10969692
TI  - Mechanisms responsible for cell volume regulation during hyperkalemic
      cardioplegic arrest.
AB  - BACKGROUND: Cardioplegia has been shown to induce significant cell swelling. This
      study tested the hypothesis that (1) the [K+][Cl-] product of the cardioplegia
      solution is the main determinant of myocyte swelling, and (2) reperfusion myocyte
      shrinkage results from a rectifying Cl- conductance. METHODS: Rabbit ventricular
      myocytes were superfused with 37 degrees C Krebs-Henseleit solution for 10
      minutes. Then cells underwent 20 minutes of superfusion with standard St. Thomas'
      solution ([K+][Cl-] product = 2566 mmol/L2) and two solutions with lower [K+][Cl
      ] product (1500 and 700 mmol/L2) at 9 degrees C. Cells were then resuperfused
      with 37 degrees C Krebs-Henseleit solution for 30 minutes. Cell volume was
      measured by videomicroscopy. RESULTS: Cells superfused with St. Thomas' having
      [K+][Cl-] products of 2,566, 1,500, and 700 mmol/L2 swelled by 9.18%+/-3.57%,
      5.51%+/-1.08%, and 1.49%+/-1.56%, respectively. Reexposure to Krebs-Henseleit
      solution caused these cells to shrink by 5.79%+/-1.41%, 8.72% +/-3.68%, and
      13.46%+/-5.60%, respectively. This shrinkage was blocked by Cl- channel blockers
      given at the onset of superfusion. CONCLUSIONS: Lowering the [K+][Cl-] product of
      St. Thomas' solution attenuated myocyte edema. Myocyte shrinkage during
      reexposure to Krebs-Henseleit solution resulted from the volume-activated Cl-
      channel.

PMID- 10969693
TI  - Do peritoneal catheters remove pro-inflammatory cytokines after cardiopulmonary
      bypass in neonates?
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) in neonates induces a cytokine-mediated
      capillary leak syndrome that can cause organ dysfunction. Removing harmful
      cytokines after CPB may attenuate this response. This study measured the
      concentrations of serum and peritoneal fluid (PF) cytokines after CPB to
      determine if harmful cytokines can be removed with peritoneal catheters. METHODS:
      Neonates (n = 18) had cardiac surgery using CPB with circulatory arrest.
      Peritoneal catheters were placed at the end of surgery to drain excess fluid.
      Serum samples were obtained before and after CPB, and PF after CPB. Cytokines
      were measured by enzyme-linked immunosorbent assay. RESULTS: Tumor necrosis
      factor-alpha and interleukin-1beta (IL-1beta) were not detected in any serum or
      PF sample. Serum concentrations of IL-6, IL-8, and IL-10 increased significantly
      after CPB. PF concentrations of IL-6 and IL-8 exceeded serum concentrations,
      whereas IL-10 concentrations were higher in the serum. There was a significant
      negative correlation between serum and PF concentrations of IL-6 after CPB (r = 
      0.63; p<0.05). CONCLUSIONS: PF has very high concentrations of the
      proinflammatory cytokines, IL-6 and IL-8, after CPB but not the antiinflammatory
      cytokine IL-10. The PF may be a depot for the harmful inflammatory cytokines
      after CPB, and removing the PF could lower serum concentrations.

PMID- 10969694
TI  - Venovenous perfusion-induced systemic hyperthermia: hemodynamics, blood flow, and
      thermal gradients.
AB  - BACKGROUND: Thermal events during extracorporeal venovenous perfusion-induced
      systemic hyperthermia (VV-PISH) were studied and related to determination of
      whole-body and regional thermal isoeffect doses. METHODS: Swine (n = 6, 77+/-4.5
      kg) were heated to a target temperature of 43 degrees C for 120 minutes using VV
      PISH. Colored microspheres were injected during preheat, heat induction,
      maintenance, cool down, and after decannulation. The esophageal, tympanic,
      rectal, pulmonary artery, bladder, bone marrow, kidney, brain, blood, lung, and
      airway temperatures were recorded continuously. The thermal dose, thermal
      exchange, metabolic heat production, heat loss to the environment, the change in
      body heat, and the thermal isoeffect dose were studied at 15-minute intervals.
      RESULTS: VV-PISH increased heart rate and cardiac output and caused a
      redistribution of blood flow favoring the thoracoabdominal organs. Greatest
      thermal exchange occurred during the heating phase (total 2,162+/-143 kJ),
      metabolic heat production contributed in all phases (274+/-9 kJ), the greatest
      change in body heat occurred during heating (1,310+/-309 kJ) with a total
      delivered thermal dose of 298+/-21 kJ, and the total whole body thermal isoeffect
      dose at 100+/-5 minutes. CONCLUSIONS: VV-PISH is feasible, is capable of
      transferring sufficient heat, causes a redistribution of blood flow favoring the
      thoracoabdominal organs, and facilitates calculation of whole-body and regional
      thermal isoeffect doses.

PMID- 10969695
TI  - Early failure of bioprosthesis by preserved mitral leaflets.
AB  - Complete preservation of the posterior mitral valve leaflet caused early
      thrombotic occlusion of two cusps of a Carpentier-Edward pericardial prosthesis
      implanted into the mitral position with subsequent bioprosthetic failure,
      necessitating reoperation.

PMID- 10969696
TI  - Bilateral sequential lung transplant for ectodermal dysplasia.
AB  - A case of bilateral sequential lung transplantation for anhidrotic ectodermal
      dysplasia is presented. The patient was a 16-year-old male with end-stage lung
      disease secondary to chronic severe respiratory infection. Although a relatively
      rare disease, the common association of fatal pulmonary compromise in those
      affected with this disorder warrants consideration of lung transplantation as a
      viable therapeutic option.

PMID- 10969697
TI  - Repair of pulmonary vein rupture after deceleration injury.
AB  - Injuries to the major pulmonary vessels are uncommon and are extremely difficult
      to manage. We report a case of an isolated pulmonary vein injury following a road
      traffic accident that was repaired successfully.

PMID- 10969698
TI  - Ventricular thrombosis and systemic embolism in bodybuilders: etiology and
      management.
AB  - Increased thrombogenicity and acute embolism are well-recognized complications of
      chronic anabolic steroid abuse. The following cases highlight such dangers in
      steroid-enhanced bodybuilders who developed intracardiac thrombosis that
      subsequently embolized. Systemic anticoagulation and surgical thrombectomy
      constituted the mainstay treatment. This represents the first report of such
      devastating cardiovascular complications after anabolic steroid abuse and their
      management.

PMID- 10969699
TI  - Radiation-induced gastrointestinal stromal sarcoma of the esophagus.
AB  - Esophageal sarcoma is an uncommon tumor, sporadically reported in the literature.
      Radiation therapy is frequently employed in the treatment of carcinoma of the
      esophagus, and the increased risk of development of sarcoma arising in irradiated
      fields is well known. However, to our knowledge, the occurrence of radiation
      associated sarcoma of the esophagus after radiation therapy for carcinoma of the
      esophagus has not been reported. We therefore report the case of a 43-year-old
      female who developed a gastrointestinal stroma sarcoma 9 years following
      radiation therapy for esophageal squamous cell carcinoma. The patient underwent
      resection of her gastrointestinal stromal sarcoma by transhiatal esophagectomy
      with cervical anastomosis and is doing well 18 months later. The increasing use
      of radiation therapy for esophageal carcinoma suggests that radiation-associated
      sarcoma of the esophagus may be seen more frequently in the future.

PMID- 10969701
TI  - Retrocardiac arteriovenous malformation causing recurrent cerebral ischemia.
AB  - A 28-year-old woman had been suffering from recurrent cerebral embolizations for
      almost 9 years. A retrocardiac arteriovenous malformation was identified as the
      source of emboli. It was supplied by chest wall veins and the right upper
      pulmonary vein, connected to the back wall of the left atrium and a possibly
      aberrant hepatic vein originating from the abdomen. The aneurysm was resected and
      all supplying veins ligated. The vein from below the diaphragm was implanted into
      the right atrium. Her postoperative course was uncomplicated. Long-term follow-up
      free from cerebrovascular events.

PMID- 10969700
TI  - Intermittent brachiocephalic vein obstruction secondary to a thymic cyst.
AB  - Mediastinal thymic cysts are usually asymptomatic and found incidentally on a
      routine chest roentgenogram. Rarely, they may cause symptoms of vascular
      obstruction. A 55-year-old woman presented with intermittent swelling in her left
      neck. The swelling was positional and was worse while supine and disappeared
      while upright. Evaluation revealed a thymic cyst causing extrinsic compression of
      the left brachiocephalic vein. The cyst was resected with complete resolution of
      the left neck swelling.

PMID- 10969702
TI  - Azygos vein diverticulum.
AB  - A 47-year-old woman, diagnosed with a diverticulum of the arch of the azygos
      vein, underwent surgical treatment. With nonspecific symptomatology, she
      presented one of the most uncommon anomalies of the large veins.

PMID- 10969703
TI  - Healing of superior vena cava defect in mediastinal seminoma with invasion.
AB  - We present an unusual case of mediastinal seminoma with direct intraluminal
      invasion into the superior vena cava (SVC) and extension to the right atrium.
      Magnetic resonance imaging demonstration of the SVC defect due to tumor invasion
      was important for determining treatment strategy because rapid posttherapeutic
      tumor regression may increase the risk of SVC rupture. Gradual healing of the SVC
      defect at the tumor entrance site was attained using a tailored treatment plan
      with radiotherapy and chemotherapy.

PMID- 10969704
TI  - Reexpansion pulmonary edema after VATS successfully treated with continuous
      positive airway pressure.
AB  - Reexpansion pulmonary edema is a well-described complication of treatment for
      pleural effusion and pneumothorax. It is very rarely described in association
      with anesthesia and video-assisted thoracoscopic surgery. The etiology is unclear
      but several mechanisms have been proposed. We report a case of reexpansion
      pulmonary edema after video-assisted thoracoscopic surgery treated successfully
      with continuous positive airway pressure.

PMID- 10969705
TI  - Psammomatous melanotic schwannoma: presentation of a rare primary lung tumor.
AB  - A 30-year-old nonsmoking man underwent a left lower lobectomy with bronchoplasty
      for an obstructing lesion of the left lower lobe. Pathology results demonstrated
      a psammomatous melanotic schwannoma, a rare pigmented neural tumor of which only
      25 cases have been reported as originating in the respiratory tract.

PMID- 10969706
TI  - Intraseptal coronary aneurysm.

PMID- 10969707
TI  - Anatomical reconstruction of aorta and pulmonary trunk in patients with an
      aortopulmonary window.
AB  - We report a modified technique for repair of aortopulmonary window in which a
      native pulmonary artery flap is created and the aortopulmonary window is
      completely divided. The pulmonary artery flap is used to reconstruct the
      ascending aorta, and the defect in the pulmonary trunk is closed with an
      autologous pericardial patch. This repair avoids the use of a fabric patch with
      its inherent disadvantages and allows anatomical reconstruction of both the
      ascending aorta and the pulmonary trunk with low risk of early or late distortion
      of the aortic and pulmonary root structures.

PMID- 10969708
TI  - Homograft-autograft valve holder.
AB  - With the increasing use of homografts and pulmonary autografts for aortic valve
      grafting it is imperative that correct orientation of the tissue valve is
      maintained during the insertion procedure. To aid in this we have developed an
      easy-to-construct and use holder for valve conduits. The holder is made from
      materials easily available in any theater. We have used this holder in more than
      50 patients and find it an essential aid to maintain orientation.

PMID- 10969709
TI  - Manubrium-sparing sternotomy and off-pump coronary artery bypass grafting in
      patients with tracheal stoma.
AB  - The presence of a tracheal stoma in patients with previous total laryngectomy who
      require cardiac operations is associated with an increased risk of wound
      complications and tracheal injuries when a full sternotomy is used. The aim of
      this report is to describe a technique of manubrium-sparing sternotomy, which can
      be used in patients undergoing coronary artery bypass grafting without
      cardiopulmonary bypass.

PMID- 10969710
TI  - External shunt for off-pump coronary artery bypass grafting: distal coronary
      perfusion catheter.
AB  - We invented a simple external shunt catheter for off-pump coronary artery bypass
      grafting. This catheter maintains coronary perfusion from femoral artery,
      prevents ischemia, reduces back-bleeding, and acts as a suture guide by
      preventing accidental missuturing of the posterior coronary wall. The insertion
      and withdraw technique is easier than intraluminal shunt. This catheter would be
      a useful tool for myocardial protection during off-pump revascularization.

PMID- 10969711
TI  - Spontaneous rupture of the thoracic aorta.
AB  - BACKGROUND: Spontaneous rupture of the thoracic aorta without trauma, aneurysm,
      or dissection is an extremely rare but catastrophic disorder. Two cases of
      spontaneous aortic rupture are presented, both treated surgically with
      satisfactory results. METHODS: A review of the English literature found 16
      patients with the diagnosis of spontaneous rupture of the thoracic aorta from
      1961 through 1998. Eighteen reported cases, including the 2 cases presented
      herein, are reviewed. RESULTS: The representative clinical picture is one of a
      middle-aged hypertensive patient with acute chest pain and collapse, with imaging
      modalities demonstrating hemopericardium, hemomediastinum, or hemothorax.
      According to the reported experiences, aortography was accurate for identifying
      the rupture site although the findings were sometimes subtle. Misdiagnosis or
      nonsurgical management resulted in the patient's death. All 8 patients who did
      not undergo aortic repair died within 3 weeks after the onset, whereas 9 of 10
      patients who underwent surgical aortic repair survived. CONCLUSIONS: For patients
      with a definitive or possible diagnosis of spontaneous rupture of the thoracic
      aorta, prompt operation is imperative through an optimal surgical approach to
      identify and repair the rupture site with appropriate circulatory support.

PMID- 10969712
TI  - Bohr effect during cooling to and rewarming from 20 degrees C cannot be ignored.

PMID- 10969713
TI  - Use of untreated pericardial patches for atrial septal defect closure.

PMID- 10969714
TI  - Coronary artery disease in identical twins.

PMID- 10969715
TI  - Ophthalmology update for primary practitioners. Part I. Update on optic neuritis.
AB  - Optic neuritis is a common cause of acute visual loss. It is typified by sudden
      onset of visual impairment and pain with eye movements, followed by spontaneous
      recovery of vision over several months. Pathologically, optic neuritis is an
      acute demyelinating event affecting the optic nerve. Objective physical findings
      are typically few, including an afferent pupillary defect or Marcus-Gunn pupil,
      whereas subjective psychophysical findings abound (ie, diminished central visual
      acuity, color vision, decreased contrast sensitivity, and visual field
      abnormalities). These characteristics have made the diagnosis of optic neuritis
      based solely on clinical grounds disquieting to practitioner and patient alike.
      In addition, the fact that optic neuritis is often associated with multiple
      sclerosis as the first clinical manifestation of disease gives further reason for
      both patient and physician anxiety. The serious nature of visual loss and the
      consequences of making the diagnosis of optic neuritis has given rise to
      extensive testing and expensive treatments. This review is intended to explore
      our current state of knowledge with regard to (1) clinical presentation, (2)
      ancillary testing, (3) therapeutic intervention, and (4) associated disease,
      specifically the risk for multiple sclerosis in the patient who presents with an
      acute optic neuritis. Finally, a suggestion guide for informing the patient and
      addressing his or her concerns will be presented.

PMID- 10969716
TI  - Ophthalmology update for the primary practitioner. Part II. Therapeutic
      management of age-related macular degeneration.

PMID- 10969717
TI  - Potentiation of brain acetylcholine neurons by Kami-Untan-To (KUT) in aged mice:
      implications for a possible antidementia drug.
AB  - The effects of a traditional Japanese herbal medicine, Kami-Untan-To (KUT), on
      brain choline (Ch) and Acetylcholine (ACh) levels in aged mice were examined.
      Further, the expression of choline acetyltransferase (ChAT) in the medial septum
      (MS), the vertical limbs of the diagonal band of Broca (VDB), and the nucleus
      basalis Meynert (NBM) was examined by immunohistochemistry. Following an oral
      administration of KUT to the aged mice for 3 months, ACh levels in the cortex,
      striatum and hippocampus were increased significantly. The density of ChAT
      immunoreactive cells located in MS, VDB, and NBM in the KUT-treated group was
      increased significantly as compared to the non-treatment group. The survival rate
      of aged mice was significantly higher in the KUT-treated group as compared to
      that in the nontreated group. Our results suggest that KUT potentiates the brain
      acetylcholinergic system, and may become a possible anti-dementia drug.

PMID- 10969718
TI  - The effects of the traditional chinese medicine, "Banxia Houpo Tang (Hange-Koboku
      To)" on the swallowing reflex in Parkinson's disease.
AB  - Swallowing disorder is common in Parkinson's disease (PD). We studied the
      swallowing disorder in PD, and tested the efficacy of Banxia Houpo Tang (BHT, a
      Chinese traditional medicine) in improving the swallowing reflex of PD patients.
      The Swallowing reflex test is a simple method used to detect swallowing disorders
      in patients with cerebrovascular disease. Because we observed previously that BHT
      significantly improved the swallowing reflex in cerebrovascular patients, we
      studied whether BHT was also effective in improving the swallowing disorder in
      patients with PD. 23 PD patients (13 males, 10 females, mean age 66.0+/-9.3,
      Hoehn & Yahr (H-Y) mean score = 2.8) were evaluated for swallowing reflex and the
      concentration of substance-P in their saliva before and after 4 weeks of BHT
      treatment. The swallowing reflex before treatment was significantly delayed,
      according to the H-Y score (Spearman's p = 0.014, R2 = 0.463). The swallowing
      reflex before BHT treatment was 3.66+/-0.98 sec, and after BHT treatment, it
      improved significantly, to 2.27+/-0.54 sec (p < 0.0001). Substance-P
      concentration in PD patients saliva before treatment was significantly lower than
      in healthy controls (p = 0.007), but showed no significant change after BHT
      treatment. Our research shows that the swallowing reflex is an effective method
      to evaluate the swallowing disorder in PD. BHT can significantly improved the
      swallowing reflex in PD patients, and therefore can be a hopeful candidate for
      preventing aspiration pneumonia in PD.

PMID- 10969719
TI  - Bone mineralization by OST-6 (OsteoCare), a herbomineral preparation, in
      experimentally induced rickets in rats.
AB  - In the present study the efficacy of OST-6 (OsteoCare), a herbomineral
      preparation, on bone mineralization in experimental rickets has been evaluated.
      This was accomplished by feeding pregnant rats and subsequently their pups with
      vitamin D and calcium deficient (VDCD) with low phosphorus diet. The parameters
      such as serum and bone mineral contents (calcium and inorganic phosphorus), serum
      alkaline phosphatase, sex hormones and histology of bone were considered. VDCD
      resulted in a significant reduction in bone and serum calcium and inorganic
      phosphorus, increased serum alkaline phosphatase and decreased sex hormones
      (testosterone in males, progesterone and oestrogen in females). Histologically
      the bone showed osteodystrophic changes and disproportionate cartilaginous
      proliferations in the epiphyseal region. Incorporation of OST-6 into feed at 5%
      concentration resulted in a complete reversal of rickets, which was substantiated
      by biochemical and histological observations. It has been concluded that OST-6 is
      useful in the management of rickets in a natural way through herbal resources.

PMID- 10969720
TI  - An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected
      commercial herbal extracts and tinctures.
AB  - Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13
      related pure plant compounds have been analyzed for their in vitro cytochrome
      P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate
      assay. Roughly 75% of the commercial products and 50% of the pure compounds
      showed significant inhibition of CYP3A4 metabolite formation. For each herbal
      product and pure compound exhibiting dose-dependency, the inhibition values were
      used to generate median inhibitory concentration (IC50) curves using linear
      regression. Among the commercial extracts, Hydrastis canadensis (goldenseal),
      Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had
      the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia
      roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and
      Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full
      strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among
      the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at
      23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole.
      Utilizing high-throughput screening methodologies for assessing CYP3A4 inhibition
      by natural products has important implications for predicting the likelihood of
      potential herbal-drug interactions, as well as determining candidates for further
      in-depth analyses.

PMID- 10969721
TI  - Antiulcerogenic effect of a hydroalcoholic extract and its organic fractions of
      Neurolaena lobata (L.) R.BR.
AB  - Neurolaena lobata is a species used widely in Caribbean folk medicine to treat
      gastric pain and ulcers. The hexane (HxF), chloroform (ClF) and aqueous (H2OF)
      fractions of a hydroalcoholic extract (HE) of N. lobata aerial parts were
      investigated for their ability to prevent ulceration of the gastric mucosa. In
      the stress-induced gastric model the HE, HxF and ClF fractions produced a
      significant reduction of gastric lesion formation by 48, 70 and 52%,
      respectively. HE, HxF and ClF fractions (41, 57 and 51%, respectively) also
      reduced significantly the gastric lesions induced by the combination of
      indomethacin and bethanechol, and the ulcers induced by HCl/ethanol solution by
      77, 86 and 83%, respectively (P < 0.05). The pylorus-ligature experiment
      demonstrated that the HE, HxF and ClF fractions changed significantly the gastric
      juice parameters, such as pH values (increases to 5.4, 4.9 and 4.8, respectively)
      and acid output (decreased by 4.6, 5.8 and 6.2 mEq mL(-1) 4h respectively) and
      gastric content (increased by 400, 410 and 390 mg, respectively) in animals. In
      the animals pre-treated orally with the HxF fraction, prostaglandin synthesis was
      increased significantly, by 104%, and free mucus production was increased by 54 %
      in the gastric mucosa (P < 0.001). The H2OF did not exhibit activity in any of
      the experimental models assayed. The data suggest that the HE and mainly the HxF
      of fractions from N. lobata present a significant anti-ulcer effect when assessed
      in these ulcer-induced models. Although the mechanism underlying this
      antiulcerogenic effect remains unknown, it seems to be related to an increased
      activity of the defensive mechanisms of the stomach, such as prostaglandin
      synthesis and mucus production.

PMID- 10969722
TI  - Prophylactic and healing properties of a new anti-ulcer compound from Enantia
      chlorantha in rats.
AB  - Decoctions prepared from Enantia chlorantha are used in the traditional treatment
      of some forms of ulcers. We have tested the anti-ulcer actions of a novel
      protoberberine-type alkaloid (7,8,-dihydro-8-hydroxypalmatine (1)) obtained from
      the bark of E. chlorantha using the HCl/ethanol, absolute ethanol and pylorus
      ligation techniques. The healing effect on chronic acetic acid-induced gastric
      ulcer was also tested. 1 (50 and 100 mg/kg) dose-dependently inhibited the
      formation of gastric ulcers induced by HCl/ethanol (35-52% inhibition), absolute
      ethanol (46-53% inhibition) and pylorus ligation (38-62% inhibition). The
      prophylactic actions were associated with significant increases in gastric mucus
      production compared with the controls. The significant inhibition of pylorus
      ligated ulcers occurred at gastric acid concentrations (83 mEq/l) previously
      known to induce severe gastric ulceration in rats. The ulcer-healing test showed
      significant macromorphological and histological acceleration of healing following
      10-day treatment with 1 (40 - 80 mg/kg). The results show that 1 has no anti
      secretory effects. The prophylactic anti-ulcer effects are associated with
      enhanced mucus production, which is an important factor in the mechanism of the
      local healing process of chronic gastric ulcers.

PMID- 10969723
TI  - Effects of tannins and related polyphenols on superoxide-induced histamine
      release from rat peritoneal mast cells.
AB  - The effects of tannins and related polyphenols on KO2- and compound 48/80-induced
      histamine release from rat peritoneal mast cells were examined. Pretreatment with
      hydrolyzable tannins (1-100 microM) significantly inhibited KO2-induced histamine
      release. Dimeric ellagitannins, which have hexahydroxydiphenoyl (HHDP) and
      valoneoyl residues and/or a valoneoyl-related acyl unit in the molecule, showed
      more potent inhibitory effects than monomeric hydrolyzable tannins. The most
      effective inhibition was exhibited by agrimoniin and euphorbin C (IC50 0.68 and
      0.80 microM), which have dehydrodigalloyl and euphorbinoyl groups, respectively,
      as well as the HHDP group. However, procyanidins, flavonoids and related
      polyphenols with small molecular weights, except for epigallocatechin gallate,
      exhibited negligible effects. Although clinically used antiallergic drugs,
      azelastine, astemizole, ketotifen and epinastine have been shown to prevent KO2
      induced histamine release, their potencies were all less than those of
      ellagitannins. An inhibitory effect on compound 48/80-induced histamine release
      was also exhibited by higher molecular weight tannins. The inhibitory effect on
      histamine release caused by different stimulants suggested that ellagitannins act
      as cell membrane stabilizers as well as radical scavengers.

PMID- 10969724
TI  - Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III
      from Curcuma longa.
AB  - Curcumin I, curcumin II (monodemethoxycurcumin) and curcumin III
      (bisdemethoxycurcumin) from Curcuma longa were assayed for their cytotoxicity,
      antioxidant and anti-inflammatory activities. These compounds showed activity
      against leukemia, colon, CNS, melanoma, renal, and breast cancer cell lines. The
      inhibition of liposome peroxidation by curcumins I-III at 100 microg/ml were 58,
      40 and 22%, respectively. The inhibition of COX-I and COX-II enzymes by the
      curcumins was observed. Curcumins I-III were active against COX-I enzyme at 125
      microg/ml and showed 32, 38.5 and 39.2% inhibition of the enzyme, respectively.
      Curcumins I-III also showed good inhibition of the COX-II enzyme at 125 mg/ml
      with 89.7, 82.5 and 58.9% inhibition of the enzyme, respectively.

PMID- 10969725
TI  - Constipating and spasmolytic effects of Khat (Catha edulis Forsk) in experimental
      animals.
AB  - The constipating and spasmolytic effects of Catha edulis Forsk (Khat) were
      investigated in whole mice and on isolated guinea pig ileum. D-amphetamine was
      employed in both experiments for comparison. The total distance travelled
      (expressed in percentage) by charcoal suspension in the gastrointestinal tract of
      mice was determined before and after khat administration. The procedure was
      repeated with amphetamine and normal saline. The results were compared.
      Amplitudes of contraction were recorded with standard spasmogens, histamine and
      carbachol, in the presence and absence of khat extract of different
      concentrations. The same was done with amphetamine. Khat extract was observed to
      reduce the total distance travelled by charcoal suspension, comparable to D
      amphetamine. The spasmogenic effects of both histamine and carbachol were
      observed to be antagonized by the khat extract in a concentration-dependent
      manner. The antispasmodic effect of khat extract was observed to be similar to
      that of D-amphetamine.

PMID- 10969726
TI  - Nantenine and papaverine differentially modify synaptosomal membrane enzymes.
AB  - Papaverine (1-[(3,4-Dimethoxyphenyl) methyl]-6,7-dimethoxyisoquinoline) and
      nantenine (O-methyldomesticine) are chemically related isoquinoline alkaloids
      displaying similar dose-dependent sedative or convulsant effects, but seem to act
      differentially on synaptosomal membrane enzymes. Na+, K+-, Mg2+- and Ca2+-ATPase
      activities were inhibited by nantenine but not by papaverine, whereas
      acetylcholinesterase activity remained unchanged by nantenine but slightly
      enhanced by papaverine. Nantenine inhibited roughly both 20-50% Ca2+- and Mg2+
      ATPase activities but 40-90% Na+, K+-ATPase activity. Kinetic analysis indicated
      that nantenine interacts with the substrate ATP for Ca2+-ATPase activity but that
      it competes with K+ for Na+, K+-ATPase activity. Given the roles of Na+, K+
      ATPase and Ca2+-ATPase in cation transport and [Ca2+]i regulation, respectively,
      the inhibitory effect of nantenine upon these enzymes may explain its convulsant
      effect though not its sedative activity. The sedative action of both nantenine
      and papaverine is hardly attributable to an effect on the synaptosomal membrane
      enzymes assayed.

PMID- 10969727
TI  - Sterility due to inhibition of sperm motility by oral administration of benzene
      chromatographic fraction of the chloroform extract of the seeds of Carica papaya
      in rats.
AB  - The contraceptive effects of benzene chromatographic fraction of the chloroform
      extract of the seeds of Carica papaya have been reported in male albino rats at
      the dose regimens 5 and 10 mg/animal/day; oral for 150 days. The body weight,
      weight of testis, epididymis, seminal vesicle and ventral prostate remained
      unaltered during the entire course of the investigation. Total suppression of
      cauda epididymal sperm motility coincided with a decrease in sperm count,
      viability and an increase in per cent abnormal spermatozoa during 60-150 days
      observation period. Minor changes in the germ cell proliferations in the testis
      and vacuolization and pyknotic nuclei in the few epithelial cells of the cauda
      epididymis were observed. Histology and biochemical composition of testis and
      accessory sex organs, haematology and serum clinical biochemistry and serum
      testosterone levels remained unchanged throughout the course of the
      investigation. Test for estrogenicity indicated mild estrogenicity. Monthly
      fertility test showed negative fertility. All the altered parameters returned to
      normal level following 60 days withdrawal of the treatment. The results suggest
      that the benzene chromatographic fraction of the chloroform extract of the seeds
      of Carica papaya exerts antifertility effects in rats without adverse toxicity
      and that the effects may be directly rendered on the spermatozoa.

PMID- 10969728
TI  - In vitro antimycobacterial activities of Physalis angulata L.
AB  - The HIV-tuberculosis co-infection has caused an impact on tuberculosis
      epidemiology all over the world and the efficacies of the therapeutic schemes
      traditionally prescribed in the treatment of tuberculosis, such as isoniazid,
      rifampicin and pyrazinamide, have decreased due to the appearance of multidrug
      resistant M. tuberculosis strains (MDR). This work is part of research on natural
      antimicrobial agents from plant extracts through bioassay-guided fractionation,
      by in vitro determination of the minimum inhibitory concentration (MIC) using the
      microdilution method with Alamar blue oxidation-reduction dye. Crude CHCl3
      Physalis angulata extracts and physalin-containing fractions displayed
      antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium
      avium, Mycobacterium kansasii, Mycobacterium malmoense and Mycobacterium
      intracellulare.

PMID- 10969729
TI  - Differential distribution of spicule matrix proteins in the sea urchin embryo
      skeleton.
AB  - Spicule matrix proteins are the products of primary mesenchyme cells, and are
      present in calcite spicules of the sea urchin embryo. To study their possible
      roles in skeletal morphogenesis, monoclonal antibodies against SM50, SM30 and
      another spicule matrix protein (29 kDa) were obtained. The distribution of these
      proteins in the embryo skeleton was observed by immunofluorescent staining. In
      addition, their distribution inside the spicules was examined by a 'spicule blot'
      procedure, direct immunoblotting of proteins embedded in crystallized spicules.
      Our observations showed that SM50 and 29 kDa proteins were enriched both outside
      and inside the triradiate spicules of the gastrulae, and also existed in the
      corresponding portions of growing spicules in later embryos and micromere
      cultures. The straight extensions of the triradiate spicules and thickened
      portions of body rods in pluteus spicules were also rich in these proteins. The
      SM30 protein was only faintly detected along the surface of spicules. By
      examination using the spicule blot procedure, however, SM30 was clearly
      detectable inside the body rods and postoral rods. These results indicate that
      SM50 and 29 kDa proteins are concentrated in radially growing portions of the
      spicules (normal to the c-axis of calcite), while SM30 protein is in the
      longitudinally growing portions (parallel to the c-axis). Such differential
      distribution suggests the involvement of these proteins in calcite growth during
      the formation of three-dimensionally branched spicules.

PMID- 10969730
TI  - Involvement of BMP-4/msx-1 and FGF pathways in neural induction in the Xenopus
      embryo.
AB  - The msx homeodomain protein is a downstream transcription factor of the bone
      morphogenetic protein (BMP)-4 signal and a key regulator for neural tissue
      differentiation. Xmsx-1 antagonizes the dorsal expression of noggin and cerberus,
      as revealed by in situ hybridization and reverse transcription-polymerase chain
      reaction assays. In animal cap explants, Xmsx-1 and BMP-4 inhibit the neural
      tissue differentiation induced by noggin or cerberus. A loss-of-function study
      using the Xmsx-1/VP-16 fusion construct indicated that neural tissue formation
      was directly induced by the injection of fusion ribonucleic acid, although the
      expression of neural cell adhesion molecule (N-CAM) in the cap was less than that
      in the cap injected with tBR or noggin. In contrast to the single cap assay,
      unexpectedly, both BMP-4 and Xmsx-1 failed to inhibit neurulation in the
      ectodermal explants to which the organizer mesoderm was attached. The results of
      cell-lineage tracing experiments indicated that the neural cells were
      differentiated from the animal pole tissue where the excess RNA of either BMP-4
      or Xmsx-1 was injected, whereas notochord was differentiated from the organizer
      mesoderm. Neural tissue differentiated from BMP-4-injected ectodermal cells
      strongly expressed posterior neural markers, such as hoxB9 and krox20, suggesting
      that the posterior neural cells differentiated regardless of the existence of the
      BMP signal. The introduction of a dominant-negative form of the fibroblast growth
      factor (FGF) receptor (XFD) into the ectodermal cells drastically reduced the
      expression of pan and posterior neural markers (N-CAM and hoxB-9) if co-injected
      with BMP-4 RNA, although XFD alone at the same dose did not shut down the
      expression of N-CAM in the combination explants. Therefore, it is proposed that
      an FGF-related molecule was involved in the direct induction of posterior neural
      tissue in the inducing signals from the organizer mesoderm in vivo.

PMID- 10969731
TI  - The vasa-like gene, olvas, identifies the migration path of primordial germ cells
      during embryonic body formation stage in the medaka, Oryzias latipes.
AB  - The medaka homolog of the Drosophila vasa gene, olvas (Oryzias latipes vas) was
      obtained using polymerase chain reaction of medaka cDNA from the testis and
      ovary. The spatio-temporal expression pattern of olvas transcripts was observed
      by in situ hybridization on gonads and embryos. The transcripts for olvas were
      exclusively detected in the cytoplasm of germ cells in the testis and ovary, not
      in gonadal somatic cells. In the early developmental stages, each blastomere
      possessed the maternal transcripts of olvas, which disappeared during gastrula
      stages. At the late gastrula stage, specific expression of olvas was observed
      only in germline cells located at the posterior shield. Embryos after the
      hybridization were examined histologically, and the distribution and migration
      path of primordial germ cells (PGC) during early stages of embryonic-body
      formation were revealed using the olvas gene as a germline cell marker. The PGC
      were translocated from the posterior shield to both sides of the embryonic body
      via the inner embryonic body in the medaka.

PMID- 10969732
TI  - Desensitization of IP3-induced Ca2+ release by overexpression of a constitutively
      active Gqalpha protein converts ventral to dorsal fate in Xenopus early embryos.
AB  - The constitutively active Gqalpha mutant construct (GqalphaQ-L) in Xenopus early
      embryos was overexpressed and the effects on dorsoventral patterning examined. It
      was found that prolonged stimulation of inositol 1,4,5-trisphosphate (IP3)-Ca2+
      signaling by overexpression of GqalphaQ-L led to desensitization of IP3-induced
      Ca2+ release (IICR). Desensitization of IICR on the ventral side specifically
      induced an ectopic dorsal axis due to the conversion of ventral marginal mesoderm
      to adopt a dorsal fate. This effect of desensitization resembles that of
      inhibitory antibodies against the IP3 receptor, as reported previously. These
      results strengthen the earlier finding that active IP3-Ca2+ signaling functions
      in ventral signaling during the early embryonic development of Xenopus.
      Furthermore, the nature of downregulation of the Xenopus IP3 receptor through
      continuous stimulation of IP3-Ca2+ signaling might play a role in regulating
      endogenous IP3-Ca2+ signaling in Xenopus early development.

PMID- 10969733
TI  - Xoom is required for epibolic movement of animal ectodermal cells in Xenopus
      laevis gastrulation.
AB  - Gastrulation is the most dynamic cell movement and initiates the body plan in
      amphibian development. In contrast to numerous molecular studies on mesodermal
      induction, the driving force of gastrulation is as yet poorly understood. A novel
      transmembrane protein, Xoom, was previously reported, which is required for
      Xenopus gastrulation. In the present study, the role of Xoom during Xenopus
      gastrulation was further examined in detail. Overexpression and misexpression of
      Xoom induced overproduction of Xoom protein, but not a changed phenotype.
      However, Xoom antisense ribonucleic acid (RNA) injection reduced the Xoom protein
      and caused gastrulation defects without any influence on the involution and
      translation levels of mesodermal marker genes. Normal migrating activity of
      dorsal mesodermal cells was recognized in the antisense RNA-injected explant.
      Morphological examination using artificial exogastrulation showed that convergent
      extension of mesodermal cells occurred normally, but the ectodermal cell layer
      significantly shrank in the antisense RNA-injected embryo. Comparison of cell
      shape among various experimental conditions showed that inhibition of cell
      spreading occurs specifically in the outer ectodermal layer of the antisense RNA
      injected embryo. Cytochemical examination indicated disorganization of F-actin in
      the ectodermal cells of the antisense RNA-injected embryo. These results suggest
      that Xoom plays an important role in the epibolic movement of ectodermal cells
      through some regulation of actin filament organization.

PMID- 10969735
TI  - Expression of testicular fatty acid-binding protein PERF 15 during germ cell
      apoptosis.
AB  - PERF 15 is a testicular germ cell specific fatty acid-binding protein (FABP)
      isolated from rat. Indirect immunofluorescent analysis of juvenile rat testis
      showed that there were some strongly PERF 15-positive spermatocytes. These cells
      showed unclear nuclear structure and were predicted to undergo apoptosis.
      Apoptosis in germ cells is an important regulatory event to limit the number of
      germ cells in the seminiferous epithelium, but the physiological significance and
      molecular mechanisms of this testicular germ cell apoptosis are poorly
      understood. To determine whether PERF 15 participates in germ cell apoptosis,
      juvenile rat testis was examined by immunohistochemical and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) methods.
      Strongly PERF 15-positive cells and TUNEL-positive cells were co-localized in
      adjacent sections. Exposure to methoxyacetic acid (MAA), known to induce
      apoptosis in spermatocytes, increased the number of strongly PERF 15-positive
      cells in 25-day-old rats' testes. Therefore, it seems that PERF 15 is involved in
      both spermatogenesis and testicular germ cell apoptosis.

PMID- 10969734
TI  - The maternal Xenopus beta-catenin signaling pathway, activated by frizzled
      homologs, induces goosecoid in a cell non-autonomous manner.
AB  - In spite of abundant evidence that Wnts play essential roles in embryonic
      induction and patterning, little is known about the expression or activities of
      Wnt receptors during embryogenesis. The isolation and expression of two maternal
      Xenopus frizzled genes, Xfrizzled-1 and Xfrizzled-7, is described. It is also
      demonstrated that both can activate the Wnt/beta-catenin signaling pathway as
      monitored by the induction of specific target genes. Activation of the beta
      Catenin pathway has previously been shown to be necessary and sufficient for
      specifying the dorsal axis of Xenopus. beta-Catenin is thought to work through
      the cell-autonomous induction of the homeobox genes siamois and twin, that in
      turn bind to and activate the promoter of another homeobox gene, goosecoid.
      However, it was found that the beta-catenin pathway regulated the expression of
      both endogenous goosecoid, and a goosecoid promoter construct, in a cell non
      autonomous manner. These data demonstrate that maternal Frizzleds can activate
      the Wnt/beta-catenin pathway in Xenopus embryos, and that induction of a known
      downstream gene can occur in a cell non-autonomous manner.

PMID- 10969736
TI  - Suppression of polydactyly of the Gli3 mutant (extra toes) by deltaEF1 homozygous
      mutation.
AB  - Digit patterning is established through multiple genetic interactions. Delta
      crystallin enhancer/E2-box factor (deltaEF1) is a zinc finger and homeodomain
      containing repressor protein, and is expressed in the posterior half of the
      forelimb bud and in the entire hindlimb bud during the early stage of limb
      development. The 6EF1-deficient mutant mice display various skeletal
      abnormalities, among which inferior ossification and abnormal patterning of
      autopodial bones are similar to those observed in Hox and Gli gene mutants. Gli3
      mutant mice, extra toes (Xt), exhibit pre-axial polydactyly losing the identity
      of digit I. It is demonstrated here that deltaEF1null(lacZ) homozygosity
      suppressed formation of the extra digit, uniquely of the hindlimb, in both
      Gli3XtJ heterozygous and homozygous mutants, but with no restoration of digit I
      identity. In Gli3XtJ mutants, the Hoxd13 expression domain was expanded more
      dramatically in homozygotes. In Gli3XtJ;deltaEF1null(lacZ) double homozygous
      mutants, Hoxd13 expression once expanded in Gli3XtJ homozygous mutant was
      reduced, more conspicuously in the hindlimbs, which may account for hindlimb
      restricted suppression of formation of the extra digit. The data suggest the
      possibility that the extent of Hoxd13 expression along the distal margin of the
      limb bud is determinative in defining the digit number.

PMID- 10969737
TI  - Loss of reactivity to pan-cadherin antibody in epidermal cells as a marker for
      metamorphic alteration of Xenopus skin.
AB  - Pan-cadherin antibodies recognize the conserved C-terminal region of the family
      of cell-cell adhesion molecules, cadherins, and have a broad spectrum of
      reactivity to the molecules. In the present study, by immunohistochemistry using
      an anti-pan cadherin monoclonal antibody (mAb), expression dynamics of cadherins
      in epidermal tissues were analyzed during metamorphosis of Xenopus laevis. At
      early stages of development, the anti-pan cadherin mAb detected signals at cell
      cell boundaries and in the cytoplasm of both trunk and tail epidermal cells.
      During metamorphosis, the immunoreactivity decreased in the trunk skin tissue but
      remained in the tail. At the climax stage, immunoreactivity was observed only in
      the regressing tail epidermis. The signals disappeared completely from the trunk
      epidermis, which had already transformed into adult-type tissue. This observation
      was confirmed by western blot analysis. A specific band was detected in the
      larval skin, but not in the adult lysate, at approximately 135 kDa in molecular
      size, corresponding to the molecular mass of cadherins. This different
      immunoreactivity in larvae and adults was observed in the epidermis of the skin,
      but not in any other tissues examined, that is, brain, kidney and liver. The
      immunoreactivity seen in larval epidermal cells was drastically downregulated by
      thyroid hormone treatment in vitro. These changes of immunoreactivity were
      specific for the C-terminal region of cadherins, suggesting intracellular
      alteration of the molecules during metamorphosis, and the anti-pan cadherin mAb
      can be a marker for larval-type epidermal cells that is applicable to analysis of
      Xenopus metamorphosis.

PMID- 10969739
TI  - Changes in the activities of protein phosphatase type 1 and type 2A in sea urchin
      embryos during early development.
AB  - In the eggs and embryos of sea urchins, the activity of protein phosphatase type
      2A (PP2A) increased during the developmental period between fertilization and the
      morula stage, decreased after the prehatching blastula stage and increased again
      after hatching. The PP2A activity changed keeping pace with alteration to the
      activities of cAMP-dependent protein kinase (A kinase), Ca2+/calmodulin-dependent
      protein kinase (CaM kinase) and casein kinase. Probably, PP2A contributes to the
      quick turning off of cellular signals because of protein phosphorylation. The
      activity of protein phosphatase type 1 (PP1) was not detectable up to the morula
      stage and appreciably increased thereafter. In the isolated nucleus fraction,
      specific activities of PP1 and PP2A were higher than in whole embryos at all
      stages in early development. Exponential increase in the number of nuclei because
      of egg cleavage probably makes PP1 activity detectable in whole embryos after the
      morula stage. In isolated nuclei, the activities of PP1 and PP2A appreciably
      decreased after hatching, whereas the activities of A kinase, Ca2+/phospholipid
      dependent protein kinase (C kinase) and CaM kinase, as well as casein kinase,
      became higher. In nuclei, cellular signals caused by protein phosphorylation
      after hatching do not seem to be turned off by these protein kinases so quickly
      as before hatching. The PP1 and PP2A in nuclei also seem to contribute to the
      elimination of signal noise.

PMID- 10969738
TI  - Ectopic activation of the transcription promoter for the testis-specific mouse
      Pgk-2 gene on elimination of a cis-acting upstream DNA region.
AB  - Transgenic mice carrying the coding sequence of beta-galactosidase, for which
      expression was driven by various upstream regions including the transcription
      promoter of the testis-specific mouse Pgk-2 gene, were generated. Expression of
      beta-galactosidase mRNA driven by the region between nucleotide positions -1404
      and +61, with respect to the transcription initiation site numbered +1, was
      examined by reverse transcription-mediated polymerase chain reaction, blot
      hybridization and in situ hybridization, and compared with that of endogenous Pgk
      2 mRNA. The results revealed that the 1.4kb DNA region is sufficient for
      determining the organ-specific, developmental stage-specific and spermatogenic
      stage-specific transcription of the mouse Pgk-2 gene. When the region between 
      684 and +61 was used to generate transgenic mice, beta-galactosidase mRNA was
      detectable not only in the testis, but also in other organs such as brain and
      lung. However, the timing and cell-type specificity of testicular expression of
      beta-galactosidase mRNA were retained in these mice. Because the region between 
      1404 and -685 repressed the Pgk-2 promoter in somatic cell-derived cell lines, it
      is suggested that the organ specificity of Pgk-2 transcription is achieved at
      least partly by negative regulation.

PMID- 10969740
TI  - Bone morphogenetic proteins and retinoic acid induce human endogenous retrovirus
      HERV-K expression in NT2D1 human embryonal carcinoma cells.
AB  - Expression of the HERV-K human endogenous retrovirus is very low in normal and
      tumor tissue, but is readily detected in testicular germ cell tumors (TGCT).
      NT2D1 human embryonal carcinoma cells represent in vitro models for the stem
      cells of TGCT, and can be differentiated by treatment with bone morphogenetic
      proteins (BMP) or retinoic acid (RA). In a search for BMP target genes in NT2D1
      cells, HERV-K was identified as an early BMP and RA target. It was shown that
      HERV-K expression was induced upon treatment of NT2D1 cells with BMP or with RA,
      but not with activin or transforming growth factor (TGF)-beta. Induction of HERV
      K expression was rapid but transient, with transcripts becoming undetectable in
      differentiated NT2D1 cultures. Thus NT2D1 cells provide a suitable in vitro
      system for the study of the factors controlling HERV-K expression during cellular
      differentiation, which may play a role in HERV-K expression in TGCT.

PMID- 10969741
TI  - Induction of proopiomelanocortin mRNA expression in animal caps of Xenopus laevis
      embryos.
AB  - To convert animal pole cells of a frog embryo from an ectodermal fate into a
      neural one, inductive signals are necessary. The alkalizing agent NH4Cl induces
      the expression of several anterior brain markers and the early pituitary marker
      XANF-2 in Xenopus animal caps. Here it is demonstrated that NH4Cl also induced
      proopiomelanocortin (POMC)-expressing cells (the first fully differentiated
      pituitary cell type) in stage 9 and 10 Xenopus animal caps, and that all-trans
      retinoic acid, a posteriorizing agent, was able to block this induction when it
      was administered within 2 h after the start of NH4Cl incubation. Thus, after 2 h,
      the fate of Xenopus animal cap cells was determined. Microinjection of
      ribonucleic acid (RNA) encoding noggin, an endogenous neural inducer, led to the
      induction of POMC gene expression in animal caps of stage 10 embryos, suggesting
      that noggin represents a candidate mesodermal signal leading to the POMC
      messenger (m) RNA producing cell type in uncommitted ectoderm. Hence, an
      alkalizing agent and a neural inducer can generate a fully differentiated POMC
      cell lineage from Xenopus animal caps.

PMID- 10969742
TI  - Egg envelope glycoprotein gp37 as a Xenopus homolog of mammalian ZP1, based on
      cDNA cloning.
AB  - The egg envelope is a kind of extracellular matrix, which surrounds growing
      oocytes, ovulated eggs and early embryos. Among the glycoprotein components of
      the Xenopus laevis egg envelope, gp43/gp41 and gp69/64 have already been shown to
      be frog homologs of the mammalian zona pellucida components ZP3 and ZP2,
      respectively. To determine the structure of another major component of egg
      envelope, gp37, the peptides isolated from the lysyl endopeptidase digests of
      gp37 were sequenced for amino acids to design degenerate primers for polymerase
      chain reaction. By reverse transcription-polymerase chain reaction with a
      poly(A)+ RNA from the ovary of a postovulated female Xenopus, a specifically
      amplified band was obtained and sequenced. The upstream and downstream sequences
      of the sequenced region were completed by 5'- and 3'-rapid amplification of cDNA
      ends, respectively. The gp37 cDNA comprises 1674 bp and contains one open reading
      frame encoding a polypeptide with 543 amino acids. The predicted amino acid
      sequence of the gp37 cDNA has a close similarity to that of mammalian ZP1.
      Northern blot and in situ hybridization studies indicated that the transcript
      (1.8 kb) is exclusively expressed in the oocytes, particularly in the
      previtellogenic young oocytes, just like the expression pattern of gp43 mRNA,
      suggesting a coordinate transcription of the gp43 and gp37 genes in Xenopus.

PMID- 10969743
TI  - Sox regulates transcription of the sea urchin arylsulfatase gene.
AB  - A 50 bp region from -194 bp to -144 bp of the arylsulfatase gene (HpArs) of the
      sea urchin, Hemicentrotus pulcherrimus, is related to the temporally regulated
      expression of this gene. This region contains a Sox (Sry-related HMG box)-binding
      site, and the introduction of sequence mutations to this site significantly
      reduced the activity of the HpArs promoter, even in the presence of the C15
      enhancer, which consists of HpOtx and CAAT motifs. A protein that binds to the
      Sox-binding site in the 50 bp region of the HpArs gene was detected in nuclear
      extracts of mesenchyme blastulae and a protein synthesized in vitro using SoxB1
      cDNA of another sea urchin, Strongylocentrotus purpuratus, also bound to this Sox
      site. These results suggest that HpSox, which is maternally expressed and remains
      abundant by the pluteus stage, is clearly implicated in regulation of the HpArs
      gene. The presence of a negatively acting cis element in this 50 bp region has
      also been detected.

PMID- 10969744
TI  - QT dispersion does not represent electrocardiographic interlead heterogeneity of
      ventricular repolarization.
AB  - INTRODUCTION: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is
      thought to reflect spatial heterogeneity of ventricular refractoriness. However,
      QTd may be largely due to projections of the repolarization dipole rather than
      "nondipolar" signals. METHODS AND RESULTS: Seventy-eight normal subjects (47+/-16
      years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38+/-15 years, 21
      women), 72 dilated cardiomyopathy patients (DCM; 48+/-15 years, 29 women), and 81
      survivors of acute myocardial infarction (AMI; 63+/-12 years, 20 women) had
      digital 12-lead resting supine ECGs recorded (10 ECGs recorded in each subject
      and results averaged). In each ECG lead, QT interval was measured under operator
      review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range,
      standard deviation, and highest-to-lowest quartile difference of QT interval in
      all measurable leads. Singular value decomposition transferred ECGs into a
      minimum dimensional time orthogonal space. The first three components represented
      the ECG dipole; other components represented nondipolar signals. The power of the
      T wave nondipolar within the total components was computed to measure spatial
      repolarization heterogeneity (relative T wave residuum, TWR). QTd was 33.6+/
      18.3, 47.0+/-19.3, 34.8+/-21.2, and 57.5+/-25.3 msec in normals, HCM, DCM, and
      AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029%+/-0.031%,
      0.067%+/-0.067%, 0.112%+/-0.154%, and 0.186%+/-0.308% in normals, HCM, DCM, and
      AMI (HCM vs DCM: NS, other P < 0.006). The correlations between QTd and TWR were
      r = -0.0446, 0.2805, -0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals,
      HCM, DCM, and AMI, respectively. CONCLUSION: Spatial heterogeneity of ventricular
      repolarization exists and is measurable in 12-lead resting ECGs. It differs
      between different clinical groups, but the so-called QT dispersion is unrelated
      to it.

PMID- 10969745
TI  - Clinical characteristics of patients with spontaneous or inducible ventricular
      fibrillation without apparent heart disease presenting with J wave and ST segment
      elevation in inferior leads.
AB  - INTRODUCTION: The clinical characteristics of three patients with spontaneous or
      inducible ventricular fibrillation (VF) without apparent heart disease, who
      presented with J wave and ST segment elevation in inferior leads, are described.
      METHODS AND RESULTS: All patients were male and experienced syncope. Their
      symptoms occurred at night or early in the morning. Holter ECG revealed
      infrequent premature ventricular complexes. Injection with disopyramide 2 mg/kg
      augmented ST segment elevation. CONCLUSION: These characteristics were very
      similar to those of patients with Brugada syndrome. These three patients with
      these specific features might have a variant of Brugada syndrome.

PMID- 10969746
TI  - Simultaneous occurrence of atrial fibrillation and atrial flutter.
AB  - INTRODUCTION: Early reports suggested that some patients with "atrial
      fibrillation/flutter" might have atrial fibrillation in one atrium and atrial
      flutter in the other. However, more recent conceptions of atrial
      fibrillation/flutter postulate that the pattern is due to a relatively organized
      (type I) form of atrial fibrillation. We report the occurrence and ECG
      manifestations of simultaneous atrial fibrillation and flutter in patients
      undergoing attempted catheter ablation of atrial flutter. METHODS AND RESULTS: In
      patients undergoing radiofrequency ablation for atrial flutter, an attempt was
      made to entrain atrial flutter by pacing in the right atrium. The arrhythmias
      observed occurred following attempts at entrainment, or spontaneously in one
      case. Twelve transient episodes of simultaneous atrial fibrillation and flutter
      were observed in five patients. The atrial fibrillation was localized to all or a
      portion of one atrium, during which the other atrium maintained atrial flutter.
      In each case, the surface 12-lead ECG reflected the right atrial activation
      pattern. No patients had interatrial or intra-atrial conduction block during
      sinus rhythm, suggesting functional intra-atrial block as a mechanism for
      simultaneous atrial fibrillation/flutter. CONCLUSION: In certain patients, the
      occurrence of transient, simultaneous atrial fibrillation and flutter is
      possible. In contrast to prior studies in which it was suggested that left atrial
      or septal activation determines P wave morphology, the results of the present
      study show that P wave morphology is determined by right atrial activation.
      Functional interatrial block appears to be a likely mechanism for this
      phenomenon.

PMID- 10969747
TI  - Atrial flutter and atrial fibrillation: two sides of a coin or one coin?

PMID- 10969748
TI  - Direct evidence of the role of virtual electrode-induced phase singularity in
      success and failure of defibrillation.
AB  - INTRODUCTION: We recently demonstrated that virtual electrode-induced phase
      singularity is responsible for arrhythmogenesis during T wave shocks and explains
      the upper and lower limits of vulnerability. Furthermore, we suggested that the
      same mechanism might be responsible for defibrillation failure. The aim of this
      study was to experimentally support this hypothesis. METHODS AND RESULTS: We used
      the voltage-sensitive dye di-4-ANEPPS and fast imaging to assess electrical
      activity in Langendorff-perfused rabbit hearts. Ventricular arrhythmias were
      induced by monophasic shocks applied during T wave. Three types of defibrillation
      shocks (n = 79) were delivered from an intravenous right ventricular electrode:
      monophasic (8 msec), optimal biphasic (8/8 msec, 2/1 leading-edge voltage ratio),
      and nonoptimal biphasic (8/8 msec, 1/1 leading-edge voltage ratio). We found that
      a monophasic shock extinguished arrhythmic pattern of electrical activity via a
      virtual electrode polarization effect. However, the virtual electrode
      polarization was likely to produce phase singularities, leading to another
      arrhythmia and defibrillation failure. Nonoptimal biphasic shocks produced
      similar effects. Optimal biphasic shocks were successful because the first phase
      of the shock erased the arrhythmia via the virtual electrodes effect, whereas the
      second phase canceled the virtual electrodes, eliminating the substrate for phase
      singularities and arrhythmia resulting from them. CONCLUSION: Our data provide
      the first experimental support of the hypothesis implicating virtual electrode
      induced phase singularity in defibrillation failure in the Langendorff-perfused
      rabbit heart. Optimal biphasic shock has a higher defibrillation efficacy because
      it does not produce virtual electrode-induced phase singularities.

PMID- 10969749
TI  - Spatially distributed dominant excitation frequencies reveal hidden organization
      in atrial fibrillation in the Langendorff-perfused sheep heart.
AB  - INTRODUCTION: Atrial fibrillation (AF) is characterized by complex wave
      propagation, yet periodic excitation suggesting a high degree of organization may
      be revealed during sustained AF. We provide a systematic quantification of the
      spatial distribution of dominant frequencies (DFs) of local excitation on the
      epicardium of the right atrial (RA) free wall and left atrial (LA) appendage of
      the isolated sheep heart during AF. The data reveal, for the first time, hidden
      organization, independent of the activation sequences or nature of electrograms.
      METHODS AND RESULTS: In 13 Langendorff-perfused sheep hearts, AF was induced in
      presence of 0.1 to 0.6 microM acetylcholine. Video movies (potentiometric dye di
      4-ANEPPS) of the RA and LA (>30,000 and >20,000 pixels, respectively) were
      obtained at 120 frames/sec and a biatrial electrogram was recorded. Spectral
      analyses were performed on movies with DF maps constructed. During AF, the
      activity formed stable discrete domains with uniform DFs within each domain.
      Acceleration of AF increased the number of domains (R = 0.81, P < 0.0001) and the
      DF variance (R = 0.63, P < 0.001), indicating a decrease in organization. Also,
      the LA was faster and more homogeneous, with smaller number of DF domains,
      compared to the RA (P < 0.00001). CONCLUSION: In this model, AF is characterized
      by multiple domains with distinct DFs on the atrial epicardium. The decrease in
      domain area with increased rate suggests that AF results from high-frequency
      impulses that undergo spectral transformations. The LA is generally faster and
      more organized than the RA, suggesting that the sources for the impulses are
      localized to the LA.

PMID- 10969750
TI  - Gender and seasonally related differences in myocardial recovery and
      susceptibility to sotalol-induced arrhythmias in isolated rabbit hearts.
AB  - INTRODUCTION: Gender differences and seasonal variations in cardiac
      electrophysiology and susceptibility to arrhythmias have been described
      clinically. The present study was undertaken to determine if there are similar
      gender and seasonally related differences in the electrophysiology of the rabbit
      heart. METHODS AND RESULTS: We analyzed epicardial electrograms, left ventricular
      endocardial monophasic action potentials (MAPs), and simulated X and Y lead ECGs
      from 145 isolated rabbit hearts studied over a period of 41 months. Hearts from
      males had seasonal increases in the duration of myocardial recovery. During the
      months of June to September compared with October to January and February to May,
      epicardial activation-recovery intervals (231.6+/-23.4 vs 215.6+/-19.2 and
      213.5+/-18.8 msec, P = 0.003), MAP durations (256.5+/-25.4 vs 237.0+/-19.6 and
      230.7+/-26.4 msec, P < 0.001), and QT intervals (278.3+/-25.6 vs 267.3+/-11.8 and
      261.3+/-13.0 msec, P = 0.037) were longer. Overall, hearts from females had
      shorter QT intervals than males (257.7+/-15.7 vs 270.1+/-20.3 msec, P < 0.001),
      and this difference was reflected in their shorter epicardial activation-recovery
      intervals and MAP durations. However, hearts from females showed a greater
      prolongation of epicardial recovery (P = 0.007) and greater incidence of
      arrhythmias (P < 0.001) with sotalol than males. Also, the incidence of
      arrhythmias was greater in the winter months October to May (P < 0.001).
      CONCLUSION: The isolated rabbit heart provides a spontaneous model of gender and
      seasonally related differences in cardiac electrophysiology and arrhythmia
      susceptibility. These differences may be related to variation in the expression
      of or regulation of the membrane ion channels mediating repolarization.

PMID- 10969752
TI  - Computer model for study of cardiac repolarization.
AB  - INTRODUCTION: We propose a new and simple method to model repolarization in the
      left ventricle and the corresponding T waves on the surface ECG. METHODS AND
      RESULTS: We modeled the cardiac cell action potentials (APs) in the left
      ventricle (LV) with differences in only the duration of the plateau phase. Using
      published experimental data on the epicardial and endocardial repolarization
      sequences, for each point on the left ventricular surface we set a different AP
      repolarization starting time, determined by the duration of the plateau phase.
      The surface source model was used to compute potentials on the surface of the
      torso, generated by repolarization of the LV. Both the torso and the LV had
      homogeneous and isotropic conductivity. We simulated T waves on the 12-lead ECG
      and compared our results with measured T waves from five normal subjects. The
      orientation and shape in each lead were reproduced. In each lead we computed the
      root mean square error between simulated and measured T waves. The average error
      across the 12 leads was small, with a mean value of 0.11 mV across all the
      subjects. CONCLUSION: Repolarization of the LV can be modeled independently of
      the depolarization sequence and AP duration gradients. This method is an easy and
      powerful tool to describe the ECG features of repolarization.

PMID- 10969751
TI  - Left atrial myocardial extension onto pulmonary veins in humans: anatomic
      observations relevant for atrial arrhythmias.
AB  - INTRODUCTION: Electrophysiologic studies have shown that spontaneous initiation
      of atrial fibrillation (AF) by ectopic beats may originate from within pulmonary
      veins. The extensions of left atrial myocardium are considered to play a role,
      but there is little detailed anatomic information available, particularly in
      humans. METHODS AND RESULTS: Thirty-nine human autopsy hearts were studied; 22
      with AF and 17 without atrial arrhythmias. The muscle fiber arrangement of the
      left atrial wall and pulmonary veins was dissected. In 18 hearts, myocardial
      sleeves were studied microscopically; in five hearts, three-dimensional
      reconstruction of the fiber arrangement in the myocardial sleeves was performed.
      Of 99 pulmonary veins examined, 96 contained a myocardial sleeve. The length of
      the sleeves was largest in the superior pulmonary veins (P < 0.01). There were no
      statistically significant differences between uniform and nonuniform muscle fiber
      arrangements. Microscopic evaluation revealed myocardial sleeves positioned on
      the adventitial side of the pulmonary vein, separated from the muscular media by
      a fibrofatty tissue plane. The most distal zone of the myocardial sleeves showed
      increasing fibrosis with encapsulation of small groups of myocardial cells and
      eventually with total disappearance of atrophic cells within fibrous tissue. Node
      like structures were not encountered. There was no relationship with presence or
      absence of AF. CONCLUSION: The observation that the peripheral zones of
      myocardial sleeves are associated with increasing connective tissue deposition
      between myocardial muscle groups suggests a degenerative change that, from the
      histologic viewpoint, fits with progressive ischemia. These changes could provide
      a basis for microreentry and, hence, for atrial arrhythmias.

PMID- 10969753
TI  - Marked reduction of ventricular defibrillation threshold by application of an
      auxiliary shock to a catheter electrode in the left posterior coronary vein of
      dogs.
AB  - INTRODUCTION: For endocardial shocks near the defibrillation threshold (DFT),
      postshock activity originates from the lateral left ventricular apex, where the
      shock field is weak. This study tested the hypothesis that an auxiliary shock
      (AS) delivered between an electrode at this site and a superior vena cava (SVC)
      electrode before the primary endocardial shock (PS) would reduce the DFT. METHODS
      AND RESULTS: In six pentobarbital-anesthetized dogs (26 to 36 kg), catheter
      electrodes were placed in the right ventricular (RV) apex and the SVC. To
      simulate transvenous introduction, a small electrode was inserted into the
      posterior cardiac vein using an epicardial approach. For dual shock treatments,
      AS (2-msec monophasic) was applied to the coronary vein electrode at different
      time intervals before a biphasic PS (4 msec/3 msec) to the RV-SVC electrodes. The
      mean DFT energy for dual shocks treatments were significantly reduced (P < 0.05)
      in comparison to the control treatment (no AS, 26.5+/-8.8 J). Mean DFT energy
      after 10 seconds of electrically induced ventricular fibrillation for dual
      shocks, in which AS and PS were separated by 1, 5, 10, and 20 msec, were 10.2+/
      4.1 J, 10.9+/-5.5 J, 11.3+/-6.3 J, and 15.4+/-7.2 J, respectively. These values
      were all significantly lower than the PS alone (26.5+/-8.8 J). CONCLUSION:
      Addition of an AS from the posterior cardiac vein before an endocardial PS
      reduces DFT energy by more than 50%. Such DFT reduction could improve therapeutic
      safety margin or permit reduction in volume of implantable cardioverter
      defibrillators.

PMID- 10969754
TI  - New approach to biphasic waveforms for internal defibrillation: fully discharging
      capacitors.
AB  - INTRODUCTION: The use of two independent, fully discharging capacitors for each
      phase of a biphasic defibrillation waveform may lead to the design of a simpler,
      smaller, internal defibrillator. The goal of this study was to determine the
      optimal combination of capacitor sizes for such a waveform. METHODS AND RESULTS:
      Eight full-discharge (95/95% tilt), biphasic waveforms produced by several
      combinations of phase-1 capacitors (30, 60, and 90 microF) and phase-2 capacitors
      (1/3, 2/3, and 1.0 times the phase-1 capacitor) were tested and compared to a
      single-capacitor waveform (120 microF, 65/65% tilt) in a pig ventricular
      fibrillation model (n = 12, 23+/-2 kg). In the full-discharge waveforms, phase-2
      peak voltage was equal to phase-1 peak voltage. Shocks were delivered between a
      right ventricular lead and a left pectoral can electrode. E50s and V50s were
      determined using a ten-step Bayesian process. Full-discharge waveforms with phase
      2 capacitors of < or =40 microF had the same E50 (6.7+/-1.7 J to 7.3+/-3.9 J) as
      the single-capacitor truncated waveform (7.3+/-3.7 J), whereas waveforms with
      phase-2 capacitors of > or =60 microF had an extremely high E50 (14.5+/-10.8 J or
      greater, P < 0.05). Moreover, of the former set of energy-efficient waveforms,
      those with phase-1 capacitors of > or =60 microF additionally exhibited V50s that
      were equivalent to the V50 of the single-capacitor waveform (344+/-65 V to 407+/
      50 V vs 339+/-83 V). CONCLUSION: Defibrillation efficacy can be maintained in a
      full-discharge, two-capacitor waveform with the proper choice of capacitors.

PMID- 10969755
TI  - Influence of wavefront dynamics on transmembrane potential characteristics during
      atrial fibrillation.
AB  - INTRODUCTION: Although computerized mapping studies have demonstrated the
      presence of multiple wavelets during atrial fibrillation (AF) and that action
      potential amplitude and duration in AF vary significantly from beat to beat, no
      study has correlated the single cell action potential changes with the patterns
      of activation during AF. METHODS AND RESULTS: We studied wavefront dynamics and
      single cell transmembrane potential (TMP) characteristics in 12 isolated perfused
      canine right atria. The endocardial surface was mapped using 477 bipolar
      electrodes while TMP was recorded with a standard glass microelectrode from an
      epicardial cell. AF was induced in the presence of acetylcholine. Successful
      simultaneous TMP recordings and activation maps were made during six episodes of
      AF and for a total of 141 activations. Large variations of TMP amplitude and
      duration were observed frequently; 34% of them have a low amplitude (<50% of the
      amplitude recorded during pacing). Low-amplitude potentials were recorded when
      the impaled cell was (1) in an area of random reentry (67%, n = 36); (2) within
      3.2 mm of the core of organized functional reentry (22%, n = 12); (3) in the
      middle of two merging wavefronts (9%, n = 5); and (4) at the point of spontaneous
      wavebreak (2%, n = 1). CONCLUSION: Large variations of TMP are observed
      frequently during in vitro AF. Low-amplitude TMPs are associated with specific
      patterns of AF activation wavefronts.

PMID- 10969756
TI  - Accessory atrioventricular node with properties of a typical accessory pathway:
      anatomic-electrophysiologic correlation.
AB  - We report an accessory AV node producing ventricular preexcitation and comprising
      the retrograde limb of AV reentrant tachycardia (AVRT). A 66-year-old man
      presented with an anteroseptal myocardial infarction and thereafter developed
      recurrent, drug-refractory AVRT requiring multiple cardioversions.
      Electrophysiologic findings were typical for a concealed anteroseptal accessory
      pathway 0.5 cm anterior to the His bundle. The patient died of intractable heart
      failure after endocardial resection for a left ventricular aneurysm and coronary
      bypass grafting. Pathologic examination revealed a para-Hisian accessory AV node
      connecting the right atrium to ventricular myocardium immediately anterior to the
      His bundle at a depth of 4 mm from the endocardium. No typical AV accessory
      pathway was found. This is the first report of an accessory AV node that
      participated in AVRT. It was deeper than typical radiofrequency catheter ablation
      lesions.

PMID- 10969757
TI  - Use of multisite electroanatomic mapping to facilitate ablation of intra-atrial
      reentry following the Mustard procedure.
AB  - Ablation of intra-atrial reentrant tachycardia following Mustard or Senning
      procedures has low success rates. The Biosense Carto system was used to map intra
      atrial reentry in a 22-year-old woman who had undergone a Mustard procedure. A
      line of block was created connecting a Mustard baffle suture line to the
      tricuspid valve annulus, which terminated the arrhythmia and prevented its
      reinitiation. Multisite electroanatomic mapping was invaluable in defining atrial
      anatomy and the intra-atrial reentrant pathway, and in creating a contiguous line
      of block. This mapping may improve ablation success rates in patients following
      the Mustard or Senning repair.

PMID- 10969758
TI  - Premature depolarization concealed in two pulmonary veins.
AB  - A case is presented in which a premature depolarization emanated from a partially
      activated left inferior pulmonary vein, activated the entire left superior
      pulmonary vein, but did not activate the atria ("concealed"). The site of
      conduction block between each vein and the left atrium was the anatomic
      atriovenous junction. At times, the same depolarization would activate the atria
      and initiate atrial fibrillation. The shortest depolarization coupling interval
      that activated the atria was significantly longer than the atrial fibrillation
      cycle length recorded in either vein. Observations in this case support two
      concepts: (1) the existence of myocardial "tracts," extending into and between
      pulmonary veins; and (2) a "mismatch" between pulmonary vein activation ingress
      and egress.

PMID- 10969759
TI  - Prevention of ventricular fibrillation by pacing in a man with Brugada syndrome.
AB  - The unique ECG appearance of Brugada syndrome is caused by failure of the dome of
      the action potential to develop. It occurs when the outward currents (mainly Ito)
      overwhelm the inward currents (mainly Ica) at the end of phase 1 of the action
      potential. Because Ito becomes less prominent at a faster rate, increased heart
      rate is associated with decreased ST segment elevation on ECG and probably
      decreased incidence of ventricular arrhythmia. We present the first report on
      prevention of ventricular fibrillation in a man with Brugada syndrome by
      overdrive pacing from his dual chamber implantable cardioverter defibrillator.

PMID- 10969760
TI  - Acquired long QT syndromes and the risk of proarrhythmia.

PMID- 10969761
TI  - Reproducible conversion from wide to narrow complex tachycardia: what is the
      mechanism?

PMID- 10969763
TI  - Intramural repolarization differences in the in vivo canine ventricle.

PMID- 10969762
TI  - Protrusion of an active fixation pacing lead into the abdominal cavity.

PMID- 10969764
TI  - Hybrid action potential etiology.

PMID- 10969765
TI  - Midkine promoter-based adenoviral vector gene delivery for pediatric solid
      tumors.
AB  - It is important to develop a system to express therapeutic genes in tumor cells
      with sufficient selectivity for cancer gene therapy. Midkine (MK) is a newly
      identified heparin-binding growth factor that is transiently expressed in the
      early stages of retinoic acid-induced differentiation of embryonal carcinoma
      cells. It has been reported that many human malignant tumors express high levels
      of MK mRNA or protein. However, no MK expression is detected in human or mouse
      liver. These interesting features of MK led us to examine the MK promoter as a
      candidate for tumor-specific gene expression. We thus developed new recombinant
      adenoviral (Ad) vectors containing either luciferase reporter gene (AdMKLuc) or
      herpes simplex thymidine kinase gene (AdMKTK) under the control of the human MK
      promoter. AdMKLuc achieved relatively high activity in Wilms' tumor (G-401) and
      neuroblastoma (SK-N-SH) cell lines. In addition, AdMKTK induced marked cell death
      in response to ganciclovir (GCV) in these same lines. Conversely, very low
      activity of the MK promoter was observed in mouse liver in vivo compared with the
      cytomegalovirus promoter. Importantly, AdMKTK + GCV did not induce liver
      toxicity, whereas substantial toxicity was seen with AdCMVTK + GCV treatment. On
      the basis of these findings, we conclude that the MK promoter is a candidate
      tumor-specific promoter for Wilms' tumor or neuroblastoma.

PMID- 10969766
TI  - Inhibition of tumor angiogenesis by a single-chain antibody directed against
      vascular endothelial growth factor.
AB  - Monoclonal antibody (Ab) directed against the vascular endothelial growth factor,
      one of the major inducers of angiogenesis, can inhibit tumor growth in mice.
      Treatment of cancer patients with monoclonal Ab requires large-scale production
      of the clean Ab and frequent application of the Ab. This might be improved by
      using single-chain Ab fragments (scFvs), which can be produced in large
      quantities in bacteria and are attractive for gene therapeutic approaches. Here
      we describe anti-vascular endothelial growth factor scFvs derived from a human
      phage-display library able to block the vascularization of the chorioallantoic
      membrane of chick embryos and reduce the growth of s.c. tumors in nude mice. This
      work opens the way to develop gene therapy-based strategies using a scFv to treat
      angiogenesis-dependent diseases.

PMID- 10969767
TI  - Loss of caspase-8 expression in highly malignant human neuroblastoma cells
      correlates with resistance to tumor necrosis factor-related apoptosis-inducing
      ligand-induced apoptosis.
AB  - Human neuroblastoma (NB) is a highly heterogeneous childhood cancer that is
      aggressively malignant or can undergo spontaneous regression that may involve
      apoptosis. NB-derived cell lines were tested for their sensitivity to apoptosis
      induced by the tumor-selective ligand tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). Noninvasive S-type cell lines (NB cell lines of
      substrate adherent phenotype) are highly sensitive to TRAIL, whereas invasive N
      type cell lines (NB cell lines of neuronal phenotype) are resistant. Whereas both
      S- and N-type cell lines express TRAIL-R2, FADD, and caspase-3 and -10, only S
      type cells express caspase-8. Reduced levels of caspase-8 protein were also
      observed in a malignant stage IV NB tumor when compared with a benign
      ganglioneuroma. The caspase-8 gene is not deleted in either N-type NB cell lines
      or high-stage NB tumors. Caspase-8 expression can be induced by demethylation
      with 5-aza-2'deoxycytidine, which enhances sensitivity to TRAIL. Therefore,
      caspase-8 expression is silenced in malignant NB, which correlates to tumor
      severity and resistance to TRAIL-induced apoptosis.

PMID- 10969768
TI  - Inactivation of retinoblastoma protein in uveal melanoma by phosphorylation of
      sites in the COOH-terminal region.
AB  - Uveal melanoma is the most common malignancy of the eye, but little is known
      about its underlying genetic defects. Melanomas of uveal origin, unlike those of
      the skin, are rarely familial and have not been linked consistently to mutations
      in tumor suppressor genes. Here, we investigated the Rb pathway in uveal
      melanoma. Most tumors displayed strong immunostaining for Rb and p16, suggesting
      that they were not mutationally inactivated. However, Rb was frequently
      phosphorylated at serine-807 and serine-811, and cyclin D1 was expressed in many
      of the tumors. Mutation of these serine residues prevented cyclin D-dependent
      phosphorylation from inactivating Rb in cultured cells. We conclude that Rb is
      frequently inactivated in uveal melanoma by phosphorylation of residues in the
      COOH-terminal region that regulate its activity, and one mechanism for this
      phosphorylation is overexpression of cyclin D.

PMID- 10969769
TI  - Absence of functional lymphatics within a murine sarcoma: a molecular and
      functional evaluation.
AB  - Despite a clinically recognized association between the lymphatics and
      metastasis, the biology of tumor-lymphatic interaction is not clearly understood.
      We report here that functional lymphatic capillaries are absent from the interior
      of a solid tumor, despite the presence within the tumor of the lymphangiogenic
      molecule vascular endothelial growth factor (VEGF)-C and endothelial cells
      bearing its receptor, VEGF receptor 3. Functional lymphatics, enlarged and VEGF
      receptor 3 positive, were detected in some tumors only at the tumor periphery
      (within 100 microm of the interface with normal tissue). We conclude that
      although lymphangiogenic factors are present, formation of functional lymphatic
      vessels is prevented, possibly due to collapse by the solid stress exerted by
      growing cancer cells.

PMID- 10969770
TI  - Mutations of the bak gene in human gastric and colorectal cancers.
AB  - The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based
      single-strand conformational polymorphism and sequencing analysis of the entire
      coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early
      stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 early
      stage and 14 advanced-stage cancers). The data herein demonstrate, for the first
      time, the mutation of the bak gene in gastric and colorectal cancers. Missense
      bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20
      (10.0%) colorectal cancers. Sequence alterations without amino acid alteration
      were observed 1 of 24 (4.2%) gastric cancers and 2 of 20 (10.0%) colorectal
      cancers. Mutations in the bak gene were observed only in advanced-stage
      gastrointestinal cancers but not in early-stage cancers. Our observations suggest
      that mutations in this gene predispose bearers to the development of
      gastrointestinal malignancies in at least a subset of the cases.

PMID- 10969771
TI  - Fenretinide-induced caspase 3 activity involves increased protein stability in a
      mechanism distinct from reactive oxygen species elevation.
AB  - Fenretinide (4-HPR) is a synthetic retinoid that displays a broad range of
      biological effects and has also demonstrated clinical efficacy as a
      chemopreventative agent. One cellular activity of 4-HPR is its ability to induce
      apoptosis. This effect has been proposed to relate to changes in intracellular
      reactive oxygen species. We show herein that a 1-h treatment of HL-60 cells with
      4-HPR led to a dose-dependent increase in hydroperoxides. Pretreatment of cells
      with the antioxidant vitamin C abolished apoptosis, measured as the appearance of
      the sub-G1 peak, in 4-HPR-treated cells. The retinoid also elicited a 3.6-fold
      increase in caspase 3 activity; however, this increase was not affected by
      vitamin C treatment. Analysis of caspase 3 protein expression by Western blot
      analysis revealed that 4-HPR resulted in a significant increase in the appearance
      of the active p17 subunit without effecting a concomitant change in p32
      procaspase 3 levels. Studies on de novo synthesis and stability of caspase 3 by
      pulse-chase and immunoprecipitation methods show that 4-HPR-treated samples had
      decreased incorporation of radioactive amino acid precursors into newly
      synthesized procaspase 3 but, during the chase (for up to 9 h), had more labeled
      caspase 3 remaining when compared with controls. These studies suggest that 4-HPR
      may effect changes in caspase 3 activity by modulating changes in zymogen
      stability by a mechanism distinct from the retinoid-elicited increase in reactive
      oxygen species.

PMID- 10969772
TI  - Cure of Burkitt's lymphoma in severe combined immunodeficiency mice by T cells,
      tetravalent CD3 x CD19 tandem diabody, and CD28 costimulation.
AB  - To increase the valency, stability, and therapeutic potential of bispecific
      antibodies, we have constructed a tetravalent tandem diabody (Tandab) that is
      specific to both human CD3 (T-cell antigen) and CD19 (B-cell marker; S. M.
      Kipriyanov et al., J. Mol. Biol., 293: 41-56, 1999). It was generated by the
      functional dimerization of a single chain molecule that contained four antibody
      variable domains (V(H) and V(L)) in an orientation that prevented intramolecular
      pairing. Compared with a previously constructed heterodimeric CD3 x CD19 diabody,
      the Tandab exhibited a higher apparent affinity to both CD3+ and CD19+ cells and
      longer blood retention when injected into mice. Biodistribution studies in mice
      bearing Burkitt's lymphoma xenografts demonstrated specific accumulation of the
      radioiodinated Tandab in a tumor site with tumor-to-blood ratios of 1.5, 8.1, and
      13.3 at 3, 18, and 24 h, respectively. Treatment of severe combined
      immunodeficiency mice bearing established Burkitt's lymphoma (5 mm in diameter)
      with human peripheral blood lymphocytes, Tandab, and anti-CD28 MAbs resulted in
      the complete elimination of tumors in all of the animals within 10 days. In
      contrast, mice receiving human peripheral blood lymphocytes in combination with
      either the diabody alone or the diabody plus anti-CD28 MAbs showed only partial
      tumor regression. These data demonstrate that the CD3 x CD19 Tandab may be a
      promising tool for the immunotherapy of human B-cell leukemias and lymphomas.

PMID- 10969773
TI  - A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c
      mouse.
AB  - We have studied the efficiency of DNA double strand break (DSB) rejoining in
      primary cells from mouse strains that show large differences in in vivo
      radiosensitivity and tumor susceptibility. Cells from radiosensitive, cancer
      prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as
      compared with cells from all of the other commonly used strains and F1 hybrids of
      C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a
      significantly reduced expression level of DNA-PKcs protein as well as a lowered
      DNA-PK activity level as compared with the other strains. In conjunction with
      published reports, these data suggest that natural genetic variation in
      nonhomologous end joining processes may have a significant impact on the in vivo
      radiation response of mice.

PMID- 10969774
TI  - Aberrant methylation of the estrogen receptor and E-cadherin 5' CpG islands
      increases with malignant progression in human breast cancer.
AB  - Loss of expression for both the estrogen receptor-alpha and E-cadherin genes has
      been linked to disease progression in human ductal breast carcinomas and has been
      associated with aberrant 5' CpG island methylation. To assess when, during
      malignant progression, such methylation begins and whether such methylation
      increases with advancing disease, we have surveyed 111 ductal carcinomas of the
      breast for aberrant methylation of the estrogen receptor-alpha and E-cadherin 5'
      CpG islands. Hypermethylation of either CpG island was evident prior to invasion
      in approximately 30% of ductal carcinoma in situ lesions and increased
      significantly to nearly 60% in metastatic lesions. Coincident methylation of both
      CpG islands also increased significantly from approximately 20% in ductal
      carcinoma in situ to nearly 50% in metastatic lesions. Furthermore, in all cases,
      the pattern of methylation displayed substantial heterogeneity, reflecting the
      well-established, heterogeneous loss of expression for these genes in ductal
      carcinomas of the breast.

PMID- 10969775
TI  - Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small
      cell lung cancer.
AB  - Genomic instability is observed in the majority of human tumors. Dysregulation of
      the mitotic spindle checkpoint is thought to be one of the mechanisms that
      facilitate aneuploidy in tumor cells. Mutations in the mitotic spindle checkpoint
      kinase BLUB1 cause a dominant negative disruption of the spindle, leading to
      chromosome instability in cancer cell lines. However, little is known about
      chromosome 2q14, the genomic region containing BUB1, in human tumors. The BUB1
      locus was evaluated in 32 colorectal cancer (CRC) and 20 non-small cell lung
      cancer (NSCLC) primary tumors using a panel of seven microsatellite repeats for
      2q, two CA repeats in BUB1, and gene mutation analysis. The 2q locus was
      allelically stable in NSCLC but relatively unstable in colorectal primary tumors
      (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed
      instability within BUB1. Previously described BUB1 mutations and polymorphisms
      were rare (< 1%) in the CRC or NSCLC tumors. Our data demonstrate 2q and BUB1
      allelic instability in CRC and indicate that mutations in BUB1 are rare causes of
      chromosome instability in CRC or NSCLC. Additional investigations may shed light
      on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal
      tumor initiation and progression.

PMID- 10969776
TI  - Inactivation of the 14-3-3 sigma gene is associated with 5' CpG island
      hypermethylation in human cancers.
AB  - The cell cycle checkpoint plays an important role in maintaining the integrity of
      cells. Recently, one of the 14-3-3 protein family members, 14-3-3sigma, was shown
      to be regulated by p53 and to play a role in the G2-M-phase checkpoint. To
      determine whether 14-3-3sigma is inactivated in human cancers, the methylation
      status of the 5' region of 14-3-3sigma was investigated in a series of gastric,
      colorectal, and hepatocellular cancer cell lines. Of 22 cell lines examined, 6
      showed aberrant methylation. The methylation status of 14-3-3sigma was found to
      be correlated with loss of expression, which was restored by 5-aza-2'
      deoxycytidine treatment. Furthermore, normal G2 arrest after DNA damage was not
      demonstrated in the cell lines with methylation. In primary gastric cancers, 14-3
      3sigma hypermethylation was observed frequently in 26 of 60 (43%) cases and
      observed more frequently in poorly differentiated adenocarcinomas (P = 0.0017).
      Our findings suggest that 14-3-3sigma is inactivated by aberrant methylation of
      the 5' region in various human cancers and that it might play an important role
      in the development of undifferentiated gastric cancers.

PMID- 10969777
TI  - Bcl-2 overexpression results in enhanced capacitative calcium entry and
      resistance to SKF-96365-induced apoptosis.
AB  - Although there is evidence that changes in cellular ionic concentrations are
      important early events in apoptosis, the regulation of ion fluxes across the
      plasma membrane during this process is poorly understood. We report here that Bcl
      2 overexpression results in up-regulation of capacitative Ca2+ entry (CCE) and
      that SKF-96365, an inhibitor of CCE, is a potent inducer of apoptosis. Cells that
      overexpress Bcl-2 are resistant to SKF-96365-mediated apoptosis and to its
      inhibition of CCE. Enhanced CCE can be reversed with ouabain, suggesting that Bcl
      2-associated plasma membrane hyperpolarization plays a role in up-regulating CCE
      and may partially explain the antiapoptotic effect of Bcl-2.

PMID- 10969778
TI  - Effect of endostatin on spontaneous tumorigenesis of mammary adenocarcinoma in a
      transgenic mouse model.
AB  - A transgenic mouse model was used to evaluate the effect of endostatin treatment
      on spontaneous tumorigenesis. In this model system, female mice develop multiple
      mammary adenocarcinomas and male mice develop prostate cancer. Female mice
      treated with mouse endostatin during a 12-15-week period showed delayed tumor
      development by 4-6 weeks and significantly decreased tumor burden. Furthermore,
      endostatin treatment reduced the number of malignant lesions per mouse. In a
      separate set of experiments, male mice treated with endostatin showed a survival
      advantage, and their life spans were prolonged by 10.5 weeks over control
      animals. These data demonstrate that mouse endostatin is effective in delaying
      spontaneous tumor development and growth.

PMID- 10969779
TI  - Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer.
AB  - Germ-line mutations in the tumor suppressor gene APC are associated with
      hereditary familial adenomatous polyposis (FAP), and somatic mutations are common
      in sporadic colorectal tumors. We now report that methylation in the promoter
      region of this gene constitutes an alternative mechanism for gene inactivation in
      colon and other tumors of the gastrointestinal tract. The APC promoter is
      hypermethylated in 18% of primary sporadic colorectal carcinomas (n = 108) and
      adenoma (n = 48), and neoplasia with APC methylation fails to express the APC
      transcript. Methylation affects only wild-type APC in 95% of cases and is not
      observed in tumors from FAP patients who have germ-line APC mutations. As with
      APC mutation, aberrant APC methylation occurs early in colorectal carcinogenesis.
      When other tumor types are analyzed (n = 208), methylation of the APC promoter is
      not restricted to the colon but is present in tumors originating elsewhere in the
      gastrointestinal tract but rarely in other tumors. Our data suggest that
      hypermethylation of APC provides an important mechanism for impairing APC
      function and further underscores the importance of the APC pathway in
      gastrointestinal tumorigenesis.

PMID- 10969780
TI  - Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to
      hypoxia and low pH.
AB  - The tumor microenvironment is characterized by regions of fluctuating and chronic
      hypoxia, low pH, and nutrient deprivation. It has been proposed that this unique
      tissue environment itself may constitute a major cause of the genetic instability
      seen in cancer. To investigate possible mechanisms by which the tumor
      microenvironment might contribute to genetic instability, we asked whether the
      conditions found in solid tumors could influence cellular repair of DNA damage.
      Using an assay for repair based on host cell reactivation of UV-damaged plasmid
      DNA, cells exposed to hypoxia and low pH were found to have a diminished capacity
      for DNA repair compared with control cells grown under standard culture
      conditions. In addition, cells cultured under hypoxia at pH 6.5 immediately after
      UV irradiation had elevated levels of induced mutagenesis compared with those
      maintained in standard growth conditions. Taken together, the results suggest
      that cellular repair functions may be impaired under the conditions of the tumor
      microenvironment, causing hypermutability to DNA damage. This alteration in
      repair capacity may constitute an important mechanism underlying the genetic
      instability of cancer cells in vivo.

PMID- 10969781
TI  - Human THP-1 monocytic leukemic cells induced to undergo monocytic differentiation
      by bryostatin 1 are refractory to proteasome inhibitor-induced apoptosis.
AB  - The ubiquitin-proteasome pathway is the principal mechanism for the degradation
      of short-lived proteins in eukaryotic cells. We demonstrated that treatment of
      THP-1 human monocytic leukemia cells with Z-LLL-CHO, a reversible proteasome
      inhibitor, induced cell death through an apoptotic pathway. Apoptosis in THP-1
      cells induced by Z-LLL-CHO involved a cytochrome c-dependent pathway, which
      included the release of mitochondrial cytochrome c, activation of caspase-9 and 
      3, and cleavage of Bcl-2 into a shortened 22-kDa fragment. Induction of apoptosis
      by protease inhibitor also was detected in U937 and TF-1 leukemia cell lines and
      cells obtained from acute myelogenous leukemia patients but not in normal human
      blood monocytes. Treatment of human blood monocytes with Z-LLL-CHO did not induce
      apoptosis or Bcl-2 cleavage in these cells that rarely proliferate.
      Interestingly, when THP-1 cells were induced to undergo monocytic differentiation
      by bryostatin 1, a naturally occurring protein kinase C activator, they were no
      longer susceptible to apoptosis induced by Z-LLL-CHO. Bryostatin 1-induced
      differentiation of THP-1 cells was associated with growth arrest, acquisition of
      adherent capacity, and expression of membrane markers characteristic of blood
      monocytes. Likewise, differentiated THP-1 cells were refractory to Z-LLL-CHO
      induced cytochrome c release, caspase activation, and Bcl-2 cleavage. Resistance
      to Z-LLL-CHO-induced apoptosis in differentiated THP-1 cells was not due to cell
      cycle arrest. These findings show that the action of proteasome inhibitors is
      mediated primarily through a cytochrome c-dependent pathway and induces apoptosis
      in leukemic cells that are not differentiated.

PMID- 10969782
TI  - Caspase-3 is essential for procaspase-9 processing and cisplatin-induced
      apoptosis of MCF-7 breast cancer cells.
AB  - In this study, we sought to investigate in more detail the role of caspase-3 in
      apoptotic processes in cultured cells and in cell-free extracts of breast cancer
      cells. We present evidence that apoptosis of caspase-3-deficient MCF-7 breast
      cancer cells is defective in response to cisplatin treatment, as determined by
      chromatin condensation, nuclear fragmentation, DNA fragmentation, and release of
      cytochrome c from the mitochondria. Reconstitution of MCF-7 cells by stable
      transfection of CASP-3 cDNA restores all these defects and results in an
      extensive apoptosis after cisplatin treatment. We further show that in extracts
      from caspase-3-deficient MCF-7 cells, procaspase-9 processing is strongly
      impaired after stimulation with either cytochrome c or recombinant caspase-8.
      Reconstitution of MCF-7 cell extracts with procaspase-3 corrects this defect,
      resulting in an efficient and complete processing of procaspase-9. Together, our
      data define caspase-3 as an important integrator of the apoptotic process in MCF
      7 breast cancer cells and reveal an essential function of caspase-3 for
      procaspase-9 processing.

PMID- 10969783
TI  - A role for protein kinase C-delta in the regulation of ornithine decarboxylase
      expression by oxidative stress.
AB  - The expression of genes that regulate cell growth, such as ornithine
      decarboxylase (ODC), can be modulated by oxidant tumor promoters. Treatment of
      murine papilloma PE cells with H2O2 led to a transient induction of ODC enzyme
      activity, which could be blocked by calphostin, a nonspecific inhibitor of
      protein kinase C (PKC). Peak activity (11-fold) occurred 5-6 h after treatment,
      followed by a rapid decline. The increase in ODC activity was associated with an
      elevation of both ODC mRNA (3-fold) and protein (7-fold). Direct involvement of
      PKC in the regulation of ODC by oxidants was determined by stable transfection of
      PE cells with a dominant-negative PKC-delta mutant. PKC-delta activity was
      completely inhibited in response to H2O2 in cells overexpressing mutant PKC-delta
      compared with cells transfected with a blank plasmid. Induction of ODC mRNA,
      protein, and activity was also completely inhibited in cells expressing the PKC
      delta mutant after H2O2 treatment. Activation of an ODC promoter-luciferase
      reporter construct by H2O2 was attenuated in mutant cells compared with control
      cells, further confirming that ODC is regulated transcriptionally by PKC-delta.
      However, fold-increases in ODC mRNA and protein were much less than the increase
      in activity, suggesting that ODC may also undergo posttranscriptional regulation
      in the presence of oxidants. Taken together, these studies provide new insight
      into the regulation of ODC by oxidants and suggest that PKC-delta may play a
      critical role in this regulation.

PMID- 10969784
TI  - Targeted disruption of the epidermal growth factor receptor inhibits development
      of papillomas and carcinomas from human papillomavirus-immortalized
      keratinocytes.
AB  - The epidermal growth factor receptor (EGF-R) is frequently overexpressed in human
      papillomavirus (HPV)-associated dysplasias and carcinomas, implying that it is
      important for the progression of keratinocytes to malignancy. We used mice with a
      targeted disruption of the EGF-R gene to directly examine its role in cell
      immortalization and tumor development. Epidermal keratinocytes were cultured from
      EGF-R knockout, heterozygous, and wild-type mice, infected with retroviruses
      encoding HPV-16 E6 and E7 oncogenes, and grafted to nude mice. E6/E7 induced
      immortalization of EGF-R wild-type cells 5-fold more efficiently than null cells.
      Immortal EGF-R null cells grew more slowly, achieved a lower saturation density,
      and were more sensitive to apoptosis than the immortalized wild-type or
      heterozygous cells. Analyses using cDNA expression arrays showed that EGF-R null
      cells expressed increased levels of RNAs encoding p21waf and insulin-like growth
      factor-binding protein-2. EGF-R-positive immortal keratinocytes formed papillomas
      in 17% (15 of 90) of skin grafts, and seven grafts progressed to squamous
      carcinoma after 6-12 months. EGF-R null keratinocytes did not form papillomas,
      but 1 of 96 grafts progressed to a squamous carcinoma after 1 year. However,
      treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate induced
      tumors in 18 and 35% of grafts containing EGF-R null or EGF-R-positive cells,
      respectively. Transduction with an activated v-Ha-ras gene, which signals
      downstream of the EGF-R, induced rapidly growing carcinomas in all grafts
      regardless of EGF-R genotype. These results directly show that the EGF-R is
      important, but not essential, for immortalization by HPV and for progression of
      immortal cells to papillomas and carcinomas.

PMID- 10969785
TI  - Human acute myeloid leukemia CD34+/CD38- progenitor cells have decreased
      sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity,
      and impaired dendritic cell transformation capacities.
AB  - The destruction of cells capable of initiating and maintaining leukemia
      challenges the treatment of human acute myeloid leukemia. Recently, CD34+/CD38-
      leukemia progenitors have been defined as new leukemia-initiating cells less
      mature than colony-forming cells. Here we show that CD34+/CD38- leukemia
      precursors have reduced in vitro sensitivity to daunorubicin, a major drug used
      in leukemia treatment, in comparison with the CD34+/CD38+ counterpart, and
      increased expression of multidrug resistance genes (mrp/lrp). These precursors
      show lower expression of Fas/Fas-L and Fas-induced apoptosis than CD34+/CD38+
      blasts. Moreover, the CD34+/CD38- leukemic subpopulation induces a weaker mixed
      leukocyte reaction of responding T-lymphocytes than the CD34+/CD38+ leukemic
      counterpart, either in a MHC-unmatched or MHC-matched settings. This weaker
      immunogenicity could be linked to lower expression on CD34+/CD38- leukemia
      precursors of major immune response molecules (MHC-DR, LFA-3, B7-1, or B7-2) than
      CD34+/CD38+ leukemic cells. Nonetheless, the susceptibility of the immature CD38-
      precursors to cytotoxicity was not different from the sensitivity of the CD38+
      counterpart. Finally, CD34+/CD38- leukemia precursors, in contrast with CD38+
      precursors, failed, under appropriate conditions, to differentiate into dendritic
      cells, a central step for antigen recognition. This is to our knowledge the first
      demonstration that the very immature phenotype of CD34+/CD38- leukemic
      progenitors confers both chemotherapy resistance and decreased capacities to
      induce an immune response. Because the susceptibility of the immature leukemia
      cells as cytotoxic targets is maintained, our data underline the importance of
      improving the initial steps of leukemia recognition, more particularly by
      defining optimal conditions of dendritic cell transformation of the very immature
      hematopoietic precursors.

PMID- 10969786
TI  - The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival
      time in nude mice transplanted with human breast cancer cells.
AB  - 1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties
      in vitro in cancer cells. However, its calcemic effect in vivo limits its
      therapeutic applications. Here, we report the efficacy of EB 1089, a low calcemic
      analogue of vitamin D, on the development of osteolytic bone metastases after
      intracardiac injection of the human breast cancer cell line MDA-MB-231 in nude
      mice. Animals injected with tumor cells were implanted simultaneously with
      osmotic minipumps containing either EB 1089 or vehicle. Both groups remained
      normocalcemic for the duration of the experiment. The total number of bone
      metastases, the mean surface area of osteolytic lesions, and tumor burden within
      bone per animal were markedly decreased in EB1089-treated mice. Furthermore,
      longitudinal analysis revealed that mice treated with EB1089 displayed a marked
      increase in survival and developed fewer bone lesions and less hind limb
      paralysis over time as compared with untreated animals. These results suggest
      that EB1089 may be beneficial in the prevention of metastatic bone lesions
      associated with human breast cancer.

PMID- 10969787
TI  - Growth inhibition of prostate cancer by an adenovirus expressing a novel tumor
      suppressor gene, pHyde.
AB  - It has been estimated that there will be > 180,400 new cases of prostate cancer
      and 31,900 prostate cancer deaths in the United States this year. New therapeutic
      strategies against locally advanced prostate cancer are desperately needed. A
      novel gene (pHyde) was identified by an improved cDNA competition hybridization
      technique for Dunning rat prostate cancer cell lines. A recombinant replication
      deficient E1/E3-deleted adenovirus type 5 containing a pHyde gene under the
      control of a truncated Rous sarcoma virus (RSV) promoter (AdRSVpHyde) was
      generated. In vitro, AdRSVpHyde significantly inhibited growth of human prostate
      cancer cell lines DU145 and LNCaP in culture. In vivo, a single injection of
      AdRSVpHyde (5 x 10(9) plaque-forming units) reduced DU145 tumors in nude mice
      remarkably compared with untreated control or viral control-treated DU145 tumors.
      Moreover, AdRSVpHyde induced apoptosis and stimulated p53 expression. These
      results together suggest that pHyde is a tumor suppressor gene that inhibits
      growth of prostate cancer and that this inhibition is at least in part due to the
      induction of apoptosis.

PMID- 10969788
TI  - Nuclear factor-kappaB/IkappaB signaling pathway may contribute to the mediation
      of paclitaxel-induced apoptosis in solid tumor cells.
AB  - Paclitaxel (Taxol), a naturally occurring antimitotic agent, has shown
      significant cell-killing activity in a variety of tumor cells through induction
      of apoptosis. The mechanism by which paclitaxel induces cell death is not
      entirely clear. Recent studies in our laboratory demonstrated that
      glucocorticoids selectively inhibited paclitaxel-induced apoptosis without
      affecting the ability of paclitaxel to induce microtubule bundling and mitotic
      arrest. This finding suggests that apoptotic cell death induced by paclitaxel may
      occur via a pathway independent of mitotic arrest. In the current study, through
      analyses of a number of apoptosis-associated genes or regulatory proteins, we
      discovered that paclitaxel significantly down-regulated IkappaB-alpha, the
      cytoplasmic inhibitor of transcription factor nuclear factor-kappaB (NF-kappaB),
      which in turn promoted the nuclear translocation of NF-kappaB and its DNA binding
      activity. In contrast, we found that glucocorticoids could antagonize paclitaxel
      mediated NF-kappaB nuclear translocation and activation through induction of
      IkappaB-alpha protein synthesis. Northern blotting analyses demonstrated that the
      steady-state level of IkappaB-alpha mRNA was not affected by paclitaxel, which
      suggests that the down-regulation of IkappaB-alpha by paclitaxel is attributable
      to protein degradation rather than suppression of transcription. Furthermore,
      through transfection assays, we demonstrated that tumor cells stably transfected
      with antisense IkappaB-alpha expression vectors remarkably increased their
      sensitivity to paclitaxel-induced apoptosis. Finally, we found that a key subunit
      of IkappaB kinase (IKK) complex, IKKbeta, was up-regulated by paclitaxel, which
      implies that paclitaxel might down-regulate IkappaB-alpha through modulation of
      IKKbeta activity. All of these results suggest that the NF-kappaB/IkappaB-alpha
      signaling pathway may contribute to the mediation of paclitaxel-induced cell
      death in solid tumor cells.

PMID- 10969789
TI  - Metabolism and pharmacokinetics of N1,N11-diethylnorspermine in a Cebus apella
      primate model.
AB  - The tissue distribution, metabolic profile, and pharmacokinetic parameters of
      i.v.-administered N1,N11-diethylnorspermine (DENSPM) are evaluated in Cebus
      apella primates, and the results are compared with data gathered from canine and
      human studies. Although the metabolic processing of DENSPM (i.e., deethylation
      and deaminopropylation) in dogs and primates is very similar, there are some
      significant differences in tissue distribution of the parent drug. In dogs, the
      organ concentration of DENSPM follows the order kidney >> liver approximately =
      lung > spleen. In the primate, the order is liver >> kidney approximately =
      spleen > lung. The difference in pharmacokinetic parameters between the species
      is profound with (area under the time-concentration curve)primate << (area under
      the time-concentration curve)dog; (terminal elimination half-life)primate <<
      (terminal elimination half-life)dog; and (mean residence time)primate << (mean
      residence time)dog. The most notable difference between dogs and primates is seen
      in the fraction of parent drug excreted unchanged in the urine, 50% in the dog
      and < 1% in the primate. However, the pharmacokinetic parameters and urinary drug
      clearance in C. apella primates are remarkably similar to those in humans. Thus,
      C. apella is established as an excellent model for assessing the metabolism,
      tissue distribution, and pharmacokinetic properties of polyamine analogues.

PMID- 10969790
TI  - Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle
      size.
AB  - The efficacy of novel cancer therapeutics has been hampered by the ability to
      deliver these agents to the tumor at effective concentrations. Liposomes have
      been used as a method to overcome some delivery issues and, in combination with
      hyperthermia, have been shown to increase drug delivery to tumors. Particle size
      has been shown to affect the delivery of liposomes, but it is not known how
      hyperthermia affects size dependence. This study investigates the effect of
      hyperthermia (42 degrees C) on the extravasation of different sized nanoparticles
      (albumin; 100-, 200-, and 400-nm liposomes) from tumor microvasculature in a
      human tumor (SKOV-3 ovarian carcinoma) xenograft grown in mouse window chambers.
      In this model (at 34 degrees C), no liposomes were able to extravasate into the
      tumor interstitium. Hyperthermia enabled liposome extravasation of all sizes. The
      magnitude of hyperthermia-induced extravasation was inversely proportional to
      particle size. Thus, at normothermia (34 degrees C), the pore cutoff size for
      this model was between 7 and 100 nm (e.g., liposomes did not extravasate). At 42
      degrees C, the pore cutoff size was increased to >400 nm, allowing all
      nanoparticles tested to be delivered to the tumor interstitium to some degree.
      With hyperthermia, the 100-nm liposome experienced the largest relative increase
      in extravasation from tumor vasculature. Hyperthermia did not enable
      extravasation of 100-nm liposomes from normal vasculature, potentially allowing
      for tumor-specific delivery. These experiments indicate that hyperthermia can
      enable and augment liposomal drug delivery to tumors and potentially help target
      liposomes specifically to tumors.

PMID- 10969791
TI  - Dendritic cells containing apoptotic melanoma cells prime human CD8+ T cells for
      efficient tumor cell lysis.
AB  - Dendritic cells (DCs) phagocytose apoptotic influenza-infected monocytes and
      cross-present influenza antigen to CD8+ T cells, generating a specific CTL
      response. We investigated whether apoptotic melanoma cells, presented by this
      mechanism, can lead to CTL responses to tumor-associated antigens and melanoma
      cells. Apoptotic HLA-A2- MEL-397 melanoma cells were internalized by HLA-A2+
      immature monocyte-derived DCs but failed to induce maturation of DCs. When
      exposed to interleukin 6, interleukin 1beta, tumor necrosis factor alpha, and
      prostaglandin E2, DCs containing apoptotic MEL-397 cell material matured normally
      [cross-presenting DCs (cp-DCs)]. Autologous CD8+ CTL lines generated with cp-DCs
      produced tumor necrosis factor when stimulated with HLA-A2-binding immunodominant
      peptides from MelanA/MART1 and MAGE-3 (expressed by MEL-397 cells) but not
      tyrosinase (absent in MEL-397). T2 target cells loaded with the respective
      peptides were lysed by these cell lines, although to a lesser extent than by CTL
      lines generated in the presence of mature DCs and peptides from melanoma
      associated h antigens. In contrast, lines generated with cp-DCs lysed HLA-A2+ MEL
      526 melanoma cells or allogenic HLA-A2+ cp-DCs efficiently, whereas the CTL
      generated with DCs and peptides had little lytic activity. Mature DCs containing
      apoptotic tumor cells may thus represent an alternative approach for the therapy
      of malignant tumors.

PMID- 10969792
TI  - Radioiodination via D-amino acid peptide enhances cellular retention and tumor
      xenograft targeting of an internalizing anti-epidermal growth factor receptor
      variant III monoclonal antibody.
AB  - The mutant epidermal growth factor receptor variant III (EGFRvIII) has been found
      on gliomas and other tumors but not on normal tissues, including those that
      express the wild-type receptor. Monoclonal antibodies (mAbs) specific for
      EGFRvIII are rapidly internalized and degraded after binding to EGFRvIII
      expressing cells. If anti-EGFRvIII mAbs are to be useful for radioimmunotherapy,
      then methods for trapping radionuclides in target cells after mAb processing are
      required. Because lysosomes are known to retain positively charged molecules, we
      have evaluated a new reagent for this purpose that uses a polycationinc peptide
      composed of D-amino acids (D-Lys-D-Arg-D-Tyr-D-Arg-D-Arg; D-KRYRR). D-KRYRR was
      first labeled using lodogen and then coupled to the murine anti-EGFRvIII mAb L8A4
      via maleimido bond formation in 60% yield. In vitro assays with the U87deltaEGFR
      cell line indicated that internalized and total cell-associated activity for the
      125I-labeled D-KRYRR-L8A4 conjugate were up to 4 and 5 times higher,
      respectively, than for L8A4 labeled with 131I using Iodogen. Paired-label
      comparisons in athymic mice with s.c. U87deltaEGFR xenografts demonstrated up to
      5-fold higher tumor uptake for mAb labeled using D-KRYRR. Higher levels of
      radioiodine activity also were observed in kidney when L8A4 was labeled using D
      KRYRR. Another paired-label study directly compared L8A4 labeled using
      radioiodinated D-KRYRR and L-KRYRR, and confirmed the role of D-amino acids in
      enhancing tumor uptake. These results suggest that D-KRYRR is a promising reagent
      for the radioiodination of internalizing mAbs, such as the anti-EGFRvIII mAb
      L8A4.

PMID- 10969793
TI  - 2-5A antisense telomerase RNA therapy for intracranial malignant gliomas.
AB  - Malignant gliomas are the most common intracranial tumors and are considered
      incurable. Therefore, exploration of novel therapeutic modalities is essential.
      Telomerase is a ribonucleoprotein enzyme that is detected in the vast majority of
      malignant gliomas but not in normal brain tissues. We, therefore, hypothesized
      that telomerase inhibition could be a very promising approach for the targeted
      therapy of malignant gliomas. Thus, 2-5A (5'-phosphorylated 2'-5'-linked
      oligoadenylate)-linked antisense against human telomerase RNA component (2-5A
      anti-hTER) was investigated for its antitumor effect on an intracranial malignant
      glioma model. 2-5A is a mediator of one pathway of IFN actions by activating
      RNase L, resulting in RNA degradation. By linking 2-5A to antisense, RNase L
      degrades the targeted RNA specifically and effectively. Prior to the experiments
      using intracranial tumor models in nude mice, we modified the in vitro and in
      vivo treatment modality of 2-5A-anti-hTER using a cationic liposome to enhance
      the effect of 2-5A-anti-hTER. Here we demonstrate that 2-5A-anti-hTER complexed
      with a cationic liposome reduced the viability of five malignant glioma cell
      lines to 20-43% within 4 days but did not influence the viability of cultured
      astrocytes lacking telomerase. Furthermore, treatment of intracranial malignant
      gliomas in nude mice with 2-5A-anti-hTER was therapeutically effective compared
      with the control (P < 0.01). These findings clearly suggest the therapeutic
      potentiality of 2-5A-anti-hTER as a novel approach for the treatment of
      intracranial malignant gliomas.

PMID- 10969794
TI  - Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells.
AB  - Ceramide has been implicated as an important component of radiation-induced
      apoptosis of human prostate cancer cells. We examined the role of the
      sphingolipid metabolites--ceramide, sphingosine, and sphingosine-1-phosphate--in
      susceptibility to radiation-induced apoptosis in prostate cancer cell lines with
      different sensitivities to gamma-irradiation. Exposure of radiation-sensitive TSU
      Pr1 cells to 8-Gy irradiation led to a sustained increase in ceramide, beginning
      after 12 h of treatment and increasing to 2.5- to 3-fold within 48 h. Moreover,
      irradiation of TSU-Pr1 cells also produced a marked and rapid 50% decrease in the
      activity of sphingosine kinase, the enzyme that phosphorylates sphingosine to
      form sphingosine-1-phosphate. In contrast, the radiation-insensitive cell line,
      LNCaP, had sustained sphingosine kinase activity and did not produce elevated
      ceramide levels on 8-Gy irradiation. Although LNCaP cells are highly resistant to
      gamma-irradiation-induced apoptosis, they are sensitive to the death-inducing
      effects of tumor necrosis factor alpha, which also increases ceramide levels in
      these cells (K. Kimura et al., Cancer Res., 59: 1606-1614, 1999). Moreover, we
      found that although irradiation alone did not increase sphingosine levels in
      LNCaP cells, tumor necrosis factor alpha plus irradiation induced significantly
      higher sphingosine levels and markedly reduced intracellular levels of
      sphingosine-1-phosphate. The elevation of sphingosine levels either by exogenous
      sphingosine or by treatment with the sphingosine kinase inhibitor N,N
      dimethylsphingosine induced apoptosis and also sensitized LNCaP cells to gamma
      irradiation-induced apoptosis. Our data suggest that the relative levels of
      sphingolipid metabolites may play a role in determining the radiosensitivity of
      prostate cancer cells, and that the enhancement of ceramide and sphingosine
      generation could be of therapeutic value.

PMID- 10969795
TI  - Targeting and therapy of carcinoembryonic antigen-expressing tumors in transgenic
      mice with an antibody-interleukin 2 fusion protein.
AB  - The purpose of this study was to engineer a bivalent single-chain
      anticarcinoembryonic antigen (CEA) antibody and an interleukin 2 (IL-2) fusion
      protein derivative for selective tumor targeting of cytokines. The variable
      domains of a high affinity anti-CEA antibody, T84.66, were used to form a single
      gene-encoded antibody [single-chain variable fragment joined to the
      crystallizable fragment, Fc (scFvFc)]. The fusion protein (scFvFc.IL-2) consisted
      of mouse IL-2-fused to the COOH-terminal end of the scFvFc. The engineered
      proteins were assembled as complete molecules and were similar to the intact anti
      CEA monoclonal antibody (Mab) in antigen-binding properties. Based on IL-2
      content of the fusion protein, its ability to support proliferation of CTLL-2
      cells was identical with that of IL-2. Despite a molecular size similar to that
      of the intact Mab, the blood clearance of the fusion protein was markedly faster
      than that of the intact Mab or scFvFc. Incubation of radiolabeled scFvFc.IL-2 but
      not the intact or scFvFc antibodies in mouse serum was accompanied by the
      appearance of complexes, suggesting that the latter may contribute to the
      accelerated clearance of the fusion protein. Biodistribution and tumor targeting
      studies were carried out in CEA-transgenic mice bearing CEA-positive murine
      tumors as well as the antigen-negative parental tumor. The bivalent anti-CEA
      scFvFc had tumor localization properties similar to those of the intact Mab.
      Although fusion of IL-2 to the COOH-terminal end of the bivalent scFvFc altered
      its pharmacokinetic properties, the fusion antibody was able to target tumors
      specifically. Maximum uptake of the intact Mab, scFvFc, and scFvFc.IL-2 in CEA
      positive tumors was 29.3 +/- 5.0, 19.5 +/- 2.1, and 6.6 +/- 0.9% injected dose/g,
      respectively. Maximum tumor localization ratios (CEA-positive/CEA-negative tumor)
      were similar for all three antibody types (4.6-6.0), demonstrating the antigen
      specificity of the tumor targeting. Significant antigen-specific targeting to CEA
      positive normal tissues of transgenic mice was not observed. Although the tumor
      targeting properties of the fusion protein were low, the growth of CEA-expressing
      (P = 0.01) but not antigen-irrelevant (P = 0.22) syngeneic tumor cells was
      inhibited after treatment of transgenic mice with the anti-CEA-IL-2 antibody.
      Therapy of CEA-expressing tumors was improved after i.v. administration of the
      fusion protein (P = 0.0001). These studies indicate that anti-CEA antibody
      directed cytokine targeting may offer an effective treatment for CEA-expressing
      carcinomas. The availability of an immunocompetent CEA transgenic mouse model
      will also help to determine the immunotherapeutic properties of these fusion
      proteins.

PMID- 10969796
TI  - Tumor necrosis factor alpha and CD40 ligand antagonize the inhibitory effects of
      interleukin 10 on T-cell stimulatory capacity of dendritic cells.
AB  - Interleukin (IL)-10 secretion by tumor cells was demonstrated to be one of the
      mechanisms by which tumor cells can escape immunological recognition and
      destruction. In dendritic cells (DCs), which are currently used for vaccination
      therapies for malignant diseases, IL-10 inhibits IL-12 production and induces a
      state of antigen-specific anergy in CD4- and CD8-positive T cells. We therefore
      analyzed the effects of different activation stimuli including lipopolysaccharide
      (LPS), tumor necrosis factor (TNF)-alpha, and CD40 ligation on IL-10 mediated
      inhibition of DC development and stimulatory capacity. In our study, the addition
      of IL-10 to the cultures containing granulocyte/macrophage-colony stimulating
      factor and IL-4 with or without LPS completely inhibited the generation of DCs
      from peripheral blood monocytes. These cells remained CD14 positive and expressed
      high levels of IL-10 receptor (IL-10R), suggesting that IL-10 mediates its
      effects by up-regulating the IL-10R. In contrast, the simultaneous incubation of
      monocytes with IL-10 and TNF-alpha or soluble CD40 ligand (sCD40L) resulted in
      the generation of CD83-positive DCs, induction of nuclear localized RelB, and
      inhibition of IL-10R up-regulation. DCs grown in the presence of IL-10 and TNF
      alpha or sCD40L elicited efficient CTL responses against viral and tumor
      associated peptide antigens, which, however, were reduced as compared with DC
      cultures generated without IL-10. IL-10 decreased the production of IL-6 and the
      expression of IL-12 in the presence of TNF-alpha or sCD40L, but it had no effect
      on IL-15, IL-18, and TNF-alpha secretion. Our results show that TNF-alpha or CD40
      ligation can antagonize the IL-10-mediated inhibition on DC function, suggesting
      that depending on activation stimuli, the presence of IL-10 does not necessarily
      result in T-cell anergy.

PMID- 10969797
TI  - Immunotherapy with dendritic cells and tumor major histocompatibility complex
      class I-derived peptides requires a high density of antigen on tumor cells.
AB  - Immunization with dendritic cells and unfractionated MHC class I-binding peptides
      derived from autologous tumor cells has been shown to induce effective antitumor
      immunity. However, the importance of the relative abundance of tumor peptides on
      the surface of tumor cells is not known. We have addressed this question using
      peptides isolated from three tumor cell lines transfected with a minigene
      encoding amino acids 33-41 of the lymphocytic choriomeningitis virus glycoprotein
      (LCMV(33-41)). The three cell lines expressed different levels of MHC class I
      molecules and had different abilities to stimulate proliferation of LCMV(33-41)
      specific T cells in vitro. We found that antitumor immune responses were best
      elicited by immunizing mice with dendritic cells and synthetic LCMV(33-41)
      peptide. Peptide preparations from a given tumor cell line conferred protection
      against challenge with the same tumor cell line. However, protective immunity to
      a different tumor could be induced only if the cell line used for peptide
      preparation presented a high relative proportion of LCMV(33-41) in association
      with MHC class I. Our results suggest that multiple peptide epitopes are required
      for the induction of an effective antitumor immune response using MHC class I
      binding peptides from tumor cells. Also, the ability to induce an antitumor
      immune response appears to correlate with the proportion, rather than the
      absolute amount, of tumor-specific peptide in the mixture used for immunization.

PMID- 10969798
TI  - Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T-cell response
      to the cancer testis antigen NY-ESO-1 in melanoma patients.
AB  - Cancer testis (CT) antigens are particularly interesting candidates for cancer
      vaccines. However, T-cell reactivity to CT antigens has been detected only
      occasionally in cancer patients, even after vaccination. A new group of CT
      antigens has been recently identified using the SEREX technique based on
      immunoscreening of tumor cDNA expression libraries with autologous sera. We have
      used fluorescent HLA-A2/peptide tetramers containing an optimized antigenic
      peptide to directly identify HLA-A2-restricted CD8+ T cells specific for the
      SEREX-defined CT antigen NY-ESO-1 in melanoma patients. High frequencies of NY
      ESO-1-specific CD8+ T cells were readily detected in peptide-stimulated
      peripheral blood mononuclear cells as well as in lymphocytes infiltrating
      melanoma lesions from patients with measurable antibody responses to NY-ESO-1. NY
      ESO-1-specific CD8+ T cells were also detectable in peptide-stimulated peripheral
      blood mononuclear cells from some seronegative patients. Whereas the frequencies
      of NY-ESO-1-specific CD8+ T cells in circulating lymphocytes were usually below
      the limit of detection by tetramer staining, the presence of NY-ESO-1 CD8+ T
      cells displaying a memory phenotype was clearly detectable ex vivo in blood from
      a seropositive patient over an extended period of time. These results indicate
      that sustained CD8+ T-cell responses to CT antigens can naturally occur both
      locally and systemically in melanoma patients.

PMID- 10969799
TI  - Analysis of specific gene mutations in the transforming growth factor-beta signal
      transduction pathway in human ovarian cancer.
AB  - Several proteins, including transforming growth factor beta (TGF-beta) receptor
      type I (RI), TGF-beta receptor type II (RII), Smad2, Smad3, and Smad4/DPC4, have
      been identified in the transduction pathway of the tumor suppressor TGF-beta.
      Mutations in TGF-beta RI, TGF-beta RII, Smad2, and Smad4/DPC4 genes are
      associated with several human cancers. The present study examines these gene
      mutations in 32 human ovarian cancers and 14 patient-matched normal tissues. For
      the first time, mutations in the Smad2 and Smad4 genes were analyzed in relation
      to human ovarian cancer. Gene mutations of TGF-beta RI, TGF-beta RII, Smad2, and
      Smad4 were analyzed using specific primers by PCR-single-strand conformational
      polymorphism (SSCP), and the results revealed a frameshift mutation at codons 276
      277 (CTCTGG-->CTGCGTGG) in exon 5 of TGF-beta RI in 10 of 32 tumor samples
      (31.3%). This mutation was associated with reduced or absent expression of TGF
      beta RI protein and p53 protein in tumor tissues. We detected SSCP variants of
      TGF-beta RII in exon 2 in 20 of 32 tumors. Sequence analysis of these variants
      revealed an A to G transition at the seventh band of intron 2. In this A to G
      polymorphism in intron 2, 12 samples (37.5%) had A/A alleles, 12 (37.5%) had A/G
      alleles, and 8 (25%) had G/G alleles. We detected Smad2 SSCP variants in exon 4
      in 12 of 32 tumors (37.5%). Sequence analysis revealed a 2-bp deletion in the
      polypyrimidine tract of intron 3, which is located at position -39 to -56 in the
      splice acceptor site of the intron 3-exon 4 junction. No SSCP variants were
      detected in the Smad4 gene. These findings suggest that mutations in the TGF-beta
      RI and in its signal transduction pathway are likely responsible for human
      ovarian carcinogenesis.

PMID- 10969800
TI  - The frequency of germ-line mutations in the breast cancer predisposition genes
      BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British
      Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.
AB  - Predisposition to prostate cancer has a genetic component, and there are reports
      of familial clustering of breast and prostate cancer. Two highly penetrant genes
      that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to
      confer an increased risk of prostate cancer of about 3-fold and 7-fold,
      respectively, in breast cancer families. Blood DNA from affected individuals in
      38 prostate cancer clusters was analyzed for germ-line mutations in BRCA1 and
      BRCA2 to assess the contribution of each of these genes to familial prostate
      cancer. Seventeen DNA samples were each from an affected individual in families
      with three or more cases of prostate cancer at any age; 20 samples were from one
      of affected sibling pairs where one was < or = 67 years at diagnosis. No germ
      line mutations were found in BRCA1. Two germ-line mutations in BRCA2 were found,
      and both were seen in individuals whose age at diagnosis was very young (< or =
      56 years) and who were members of an affected sibling pair. One is a 4-bp
      deletion at base 6710 (exon 11) in a man who had prostate cancer at 54 years, and
      the other is a 2-bp deletion at base 5531 (exon 11) in a man who had prostate
      cancer at 56 years. In both cases, the wild-type allele was lost in the patient's
      prostate tumor at the BRCA2 locus. However, intriguingly, in neither case did the
      affected brother also carry the mutation. Germ-line mutations in BRCA2 may
      therefore account for about 5% of prostate cancer in familial clusters.

PMID- 10969801
TI  - Comparative genomic hybridization analysis of 38 breast cancer cell lines: a
      basis for interpreting complementary DNA microarray data.
AB  - Breast cancer cell lines provide a useful starting point for the discovery and
      functional analysis of genes involved in breast cancer. Here, we studied 38
      established breast cancer cell lines by comparative genomic hybridization (CGH)
      to determine recurrent genetic alterations and the extent to which these cell
      lines resemble uncultured tumors. The following chromosomal gains were observed:
      8q (75%), 1q (61%), 20q (55%), 7p (44%), 3q (39%), 5p (39%), 7q (39%), 17q (33%),
      1p (30%), and 20p (30%), and the most common losses were: 8p (58%), 18q (58%), 1p
      (42%), Xp (42%), Xq (42%), 4p (36%), 11q (36%), 18p (33%), 10q (30%), and 19p
      (28%). Furthermore, 35 recurrent high-level amplification sites were identified,
      most often involving 8q23 (37%), 20q13 (29%), 3q25-q26 (24%), 17q22-q23 (16%),
      17q23-q24 (16%), 1p13 (11%), 1q32 (11%), 5p13 (11%), 5p14 (11%), 11q13 (11%),
      17q12-q21 (11%), and 7q21-q22 (11%). A comparison of DNA copy number changes
      found in the cell lines with those reported in 17 published studies (698 tumors)
      of uncultured tumors revealed a substantial degree of overlap. CGH copy number
      profiles may facilitate identification of important new genes located at the
      hotspots of such chromosomal alterations. This was illustrated by analyzing
      expression levels of 1236 genes using cDNA microarrays in four of the cell lines.
      Several highly overexpressed genes (such as RCH1 at 17q23, TOPO II at 17q21-q22,
      as well as CAS and MYBL2 at 20q13) were involved in these recurrent DNA
      amplifications. In conclusion, DNA copy number profiles were generated by CGH for
      most of the publicly available breast cancer cell lines and were made available
      on a web site (http://www.nhgri.nih.gov/DIR/CGB/++ +CR2000). This should
      facilitate the correlative analysis of gene expression and copy number as
      illustrated here by the finding by cDNA microarrays of several overexpressed
      genes that were amplified.

PMID- 10969802
TI  - Delineation of the 6p22 amplification unit in urinary bladder carcinoma cell
      lines.
AB  - Eight cell lines from transitional cell carcinoma of the urinary bladder were
      analyzed by comparative genomic hybridization. All tumor lines exhibited frequent
      chromosome gains (11.5/cell line) and losses (8.4/cell line). In six cell lines,
      gain of chromosome 5p was associated with gains of 6p and 20q. In five of these
      cell lines, amplification of parts of 6p was observed. Cytogenetic investigation
      combined with fluorescence in situ hybridization analysis revealed typical marker
      chromosomes with homogeneously staining regions (HSRs) containing material from
      6p. By hybridizing individual yeast artificial chromosome probes from a
      chromosome 6p contig to these HSRs, a contig of three yeast artificial
      chromosomes common to all 6p HSRs was identified that spans less than 2 Mb. The
      genes SOX4 and PRL were shown to map to this region and to be coamplified in the
      cell lines. However, SOX4 was not overexpressed in any cell line and PRL was not
      expressed at all. Thus, the presumptive 6p oncogene remains to be conclusively
      identified.

PMID- 10969803
TI  - Transforming growth factor-beta1 recruits histone deacetylase 1 to a p130
      repressor complex in transgenic mice in vivo.
AB  - Transforming growth factor (TGF)-beta1 functions as a tumor suppressor in vivo.
      Using transgenic mice, we show that hepatic TGF-beta1 overexpression inhibits
      abundance of the cyclin-dependent kinase activating tyrosine phosphatase cdc25A
      protein. The reduction in cdc25A protein levels was associated with increased
      binding of histone deacetylase 1 to p130 in the hepatic extracts. In cultured
      cells, HDAC1/p130 overexpression inhibited activity of the cdc25A promoter
      through an E2F site. TGF-beta1 treatment enhanced p130 binding to the cdc25A
      promoter E2F site assessed in chromatin immunoprecipitation assays. Hepatic
      proliferation induced by partial hepatectomy was associated with a decrease in
      the amount of HDAC1 bound to p130, without a significant decrease in p130
      abundance, suggesting that HDAC1 binding to p130 may be regulated by
      proliferative stimuli. The induction of cdc25A abundance induced by partial
      hepatectomy correlated with the induction of DNA synthesis. These studies suggest
      that TGF-beta1 may enhance HDAC1 binding to p130 in vivo, thereby inhibiting
      cdc25A gene expression. TGF-beta1 regulation of HDAC1/pocket protein associations
      may provide a link between chromatin remodeling proteins and cdk inhibition
      through induction of cdc25A in vivo.

PMID- 10969804
TI  - p53 dependence of topoisomerase I recruitment in vivo.
AB  - DNA damage is attended by rapid recruitment of endogenous type I topoisomerase
      (topo I) into covalent cleavage complexes with genomic DNA in vivo. In contrast,
      endogenous topoisomerase II alpha and beta are not stimulated by DNA damage. We
      show that topo I and p53 are able to associate at arrested topo I-genomic DNA
      covalent complexes in vivo, suggesting that p53 directly stimulates topo I
      activity and damage to the genome of the afflicted cell. Moreover, cells that
      express wild-type p53 are most proficient at recruiting topo I after DNA damage;
      however, the p53 dependence is conditional because topo I recruitment after DNA
      damage can be restored if p53 mutant cells (containing a single mutant allele)
      are artificially held in G1. In contrast, p53 null mutants do not recruit topo I
      after DNA damage under any conditions (although camptothecin-dependent topo I/DNA
      complexes readily form in the nulls). These results show that topo I activation
      after DNA damage depends on the p53 status of the cell. It also depends upon the
      cell cycle in a way that is very different from that observed with DNA
      replication-dependent, camptothecin-mediated DNA breaks. The data suggest a model
      where p53 activates topo I, which inflicts additional genomic damage after the
      initial UV damage events. Topoisomerases therefore contribute to the p53
      commitment to apoptosis, and topo I might assist in elimination of DNA-damaged
      cells as part of the cellular proofreading function inherent in the p53 pathway.

PMID- 10969805
TI  - Induction of retinoic acid receptor-alpha by granulocyte macrophage colony
      stimulating factor in human myeloid leukemia cell lines.
AB  - We reported previously that treatment with all-trans retinoic acid (ATRA) and
      granulocyte macrophage colony-stimulating factor (GM-CSF) induces differentiation
      of human myeloblastic leukemia ML-1 cells to granulocytes, whereas treatment with
      ATRA alone induces practically no differentiation of these cells. To investigate
      the mechanism of the synergistic effect of these factors, we examined the effect
      of GM-CSF on retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in ML
      1 cells. We reveal that GM-CSF induces the expression of RAR alpha mRNA and
      protein and stimulates the binding of nuclear proteins to direct repeat 5, a
      consensus sequence with high affinity for RAR-RXR heterodimers. Furthermore,
      expression of CD38 mRNA mediated through RAR alpha is induced synergistically by
      treatment with ATRA + GM-CSF. These results suggest that GM-CSF stimulates
      transcriptional activity mediated via RAR alpha in ML-1 cells. The induction of
      RAR alpha by GM-CSF may therefore be a mechanism for stimulation by GM-CSF. The
      induction of RAR alpha by GM-CSF was also detected in other myeloid leukemia cell
      lines (THP-1 and KG-1) that showed a synergistic effect similar to that seen in
      ML-1 cells in response to ATRA + GM-CSF. We also found that GM-CSF induced the
      expression of RAR alpha in blood cells obtained from patients with acute myeloid
      leukemia. This activity of GM-CSF may serve as a useful adjunct to
      differentiation therapy for retinoic acid-nonresponsive leukemias.

PMID- 10969806
TI  - Suppression of human prostate cancer cell growth by alpha1-adrenoceptor
      antagonists doxazosin and terazosin via induction of apoptosis.
AB  - Recent evidence from our laboratory has demonstrated that alpha1-adrenoceptor
      antagonists doxazosin and terazosin induced apoptosis in prostate epithelial and
      smooth muscle cells in patients with benign prostatic hypertrophy (BPH; J. Urol.,
      159: 1810-1815, 1998; J. Urol., 161: 2002-2007, 1999). In this study, we
      investigated the biological action of three alpha1-adrenoceptor antagonists,
      doxazosin, terazosin, and tamsulosin, against prostate cancer cell growth. The
      antigrowth effect of the three alpha1-adrenoceptor antagonists was examined in
      two human prostate cancer cell lines, PC-3 and DU-145, and a prostate smooth
      muscle cell primary culture, SMC-1, on the basis of: (a) cell viability assay;
      (b) rate of DNA synthesis; and (c) induction of apoptosis. Our results indicate
      that treatment of prostate cancer cells with doxazosin or terazosin results in a
      significant loss of cell viability, via induction of apoptosis in a dose
      dependent manner, whereas tamsulosin had no effect on prostate cell growth.
      Neither doxazosin nor terazosin exerted a significant effect on the rate of cell
      proliferation in prostate cancer cells. Exposure to phenoxybenzamine, an
      irreversible inhibitor of alpha1-adrenoceptors, does not abrogate the apoptotic
      effect of doxazosin or terazosin against human prostate cancer or smooth muscle
      cells. This suggests that the apoptotic activity of doxazosin and terazosin
      against prostate cells is independent of their capacity to antagonize alpha1
      adrenoceptors. Furthermore, an in vivo efficacy trial demonstrated that doxazosin
      administration (at tolerated pharmacologically relevant doses) in SCID mice
      bearing PC-3 prostate cancer xenografts resulted in a significant inhibition of
      tumor growth. These findings demonstrate the ability of doxazosin and terazosin
      (but not tamsulosin) to suppress prostate cancer cell growth in vitro and in vivo
      by inducing apoptosis without affecting cell proliferation. This evidence
      provides the rationale for targeting both drugs, already in clinical use and with
      established adverse-effect profiles, against prostatic tumors for the treatment
      of advanced prostate cancer.

PMID- 10969807
TI  - Tumor oxygenation in hormone-dependent tumors during vascular endothelial growth
      factor receptor-2 blockade, hormone ablation, and chemotherapy.
AB  - Tumor oxygenation is critical for tumor survival as well as for response to
      therapy, e.g., radiation therapy. Hormone ablation therapy in certain hormone
      dependent tumors and antiangiogenic therapy lead to vessel regression and have
      also shown beneficial effects when combined with radiation therapy. These
      findings are counterintuitive because vessel regression should reduce oxygen
      tension (pO2) in tumors, decreasing the effectiveness of radiotherapy. Here we
      report on the dynamics of pO2 and oxygen consumption in a hormone-dependent tumor
      following hormone ablation and during treatment with an anti-VEGFR-2 monoclonal
      antibody (mAb) or a combination of doxorubicin and cyclophosphamide; the latter
      combination is not known to cause vessel regression at doses used clinically.
      Androgen-dependent male mouse mammary carcinoma (Shionogi) was implanted into
      transparent dorsal skin-fold chambers in male severe combined immunodeficient
      mice. Thirteen days after the tumors were implanted, mice were treated with
      antiangiogenic therapy (anti-VEGFR-2 mAb, 1.4 mg/30 g body weight), hormone
      ablation by castration, or doxorubicin (6.5 mg/kg every 7 days) and
      cyclophosphamide (100 mg/kg every 7 days). A non-invasive in vivo method was used
      to measure pO2 profiles and to calculate oxygen consumption rates (Q(O2)) in
      tumors. Tumors treated with anti-VEGFR-2 mAb exhibited vessel regression and
      became hypoxic. Initial vessel regression was followed by a "second wave" of
      angiogenesis and increases in both pO2 and Q(O2). Hormone ablation led to tumor
      regression followed by an increase in pO2 coincident with regrowth. Chemotherapy
      led to tumor growth arrest characterized by constant Q(O2) and elevated pO2. The
      increased pO2 during anti-VEGFR-2 mAb and hormone ablation therapy may explain
      the observed beneficial effects of combining antiangiogenic or hormone therapies
      with radiation treatment. Thus, understanding the microenvironmental dynamics is
      critical for optimal scheduling of these treatment modalities.

PMID- 10969808
TI  - Genetic reprogramming in pathways of colonic cell maturation induced by short
      chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and
      implications for chemoprevention of colon cancer.
AB  - The short-chain fatty acid butyrate, produced by microbial fermentation of
      dietary fiber in the large intestine, is a physiological regulator of major
      pathways of colonic epithelial cell maturation: cell cycle arrest, lineage
      specific differentiation, and apoptosis. Microarray analysis of 8,063 sequences
      demonstrated a complex cascade of reprogramming of SW620 colonic epithelial cells
      upon treatment with butyrate characterized by the progressive recruitment of gene
      sets as a function of time. Comparison with the effects of trichostatin A, in
      conjunction with differences in the kinetics of alteration of histone acetylation
      induced by butyrate and trichostatin A, identified subsets of induced and
      repressed genes likely coordinately regulated by altered histone acetylation. The
      butyrate response was also compared in detail with that of sulindac, a
      nonsteroidal anti-inflammatory drug with significant chemopreventive activity for
      colon cancer, and curcumin, a component of mustard and curry structurally and
      functionally related to sulindac that also has chemopreventive activity. Although
      gene clusters were identified that showed similar responses to butyrate and
      sulindac, the data were characterized by the extensive differences in the effects
      of the two agents. This was striking for functional classes of genes involved in
      signaling pathways and in cell cycle progression, although butyrate and sulindac
      induce a similar G0-G1 arrest, elevation of beta-catenin-Tcf signaling, and
      apoptotic cascade. As regards cell cycle arrest, the underlying mechanism in
      response to butyrate was most similar to that of the Caco-2 cell line that had
      spontaneously undergone a G0-G1 arrest and least similar to the G2-M arrest
      stimulated by curcumin. Thus, high-throughput microarray analysis of gene
      expression profiles can be used to characterize and distinguish the mechanisms of
      response of colonic epithelial cells to physiological and pharmacological
      inducers of cell maturation. This has important implications for characterization
      of chemopreventive agents and recognition of potential toxicity and synergies.
      The data bases, gene clusters, and analyses are available at http://
      sequence.aecom.yu.edu/genome/.

PMID- 10969809
TI  - Insulin-like growth factor-I is an autocrine regulator of chromogranin A
      secretion and growth in human neuroendocrine tumor cells.
AB  - Carcinoid tumors are predominantly found in the gastrointestinal tract and are
      characterized by hypersecretion of various substances, including bioamines and
      neuropeptides, leading to functional tumor disease. Here, we demonstrate that
      human BON carcinoid tumor cells express functionally active insulin-like growth
      factor-I (IGF-I) receptors and secrete IGF-I, suggesting an autocrine action of
      this growth factor. The IGF-I receptor was functionally active. IGF-I stimulated
      phosphatidylinositol 3-kinase (PI3-kinase), p70 S6 kinase (p70s6k), and
      extracellular signal-regulated kinase 2 activity in BON cells. Furthermore,
      immunoneutralization of endogenously released IGF-I markedly reduced the high
      basal activity of p70s6k and extracellular signal-regulated kinase 2 in serum
      starved BON cells. Exogenously added IGF-I induced a marked increase in
      chromogranin A secretion, a marker protein for neuroendocrine secretion, by a
      process that was largely dependent on PI3-kinase activity. In addition,
      immunoneutralization of endogenously released IGF-I markedly reduced basal
      chromogranin A release by BON cells. Thus, the autocrine IGF-I loop regulates
      basal neuroendocrine secretion in BON cells. Next, we investigated the role of
      IGF-I as a growth promoting agent for BON cells. Our data demonstrate that IGF-I
      stimulates anchorage-dependent and anchorage-independent growth of BON cells by a
      pathway that involves PI3-kinase, mammalian target of rapamycin/p70s6k, and
      mitogen-activated protein kinase kinase 1 activity. Interestingly, mitogen
      activated protein kinase kinase 1 activity was less important for anchorage
      independent growth of BON cells. Endogenously released IGF-I was found to be
      largely responsible for autonomous growth of BON cells in serum-free medium and
      for the constitutive expression of cyclin D1 in these cells. In conclusion, IGF-I
      is a major autocrine regulator of neuroendocrine secretion and growth of human
      BON neuroendocrine tumor cells. Because our data also demonstrate that a
      significant proportion of neuroendocrine tumors express the IGF-I receptor and
      its ligand, interference with this pathway could be useful in the treatment of
      hypersecretion syndromes and growth of human neuroendocrine tumors.

PMID- 10969810
TI  - Scintigraphic imaging of the hypoxia marker (99m)technetium-labeled 2,2'-(1,4
      diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; prognox):
      noninvasive detection of tumor response to the antivascular agent 5,6
      dimethylxanthenone-4-acetic acid.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA
      4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical
      trial. One of the challenges in clinical evaluation of antivascular agents is the
      monitoring of tumor blood flow inhibition in individual patients. This study
      investigates, using mouse models, whether a new marker for tissue hypoxia,
      (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime
      (99mTc-labeled HL-91; Prognox)] has potential for the scintigraphic monitoring of
      tumor response to antivascular agents. Determination of radioactivity in
      dissected tissues 3 h after DMXAA (80 micromol/kg) or CA-4-P (227 micromol/kg)
      was injected indicated that both drugs inhibited blood flow (86RbCl uptake; 84
      and 87%, respectively) and increased 99mTc-labeled HL-91 levels (350 and 300%,
      respectively) selectively in murine RIF-1 tumors. Planar imaging of 99mTc-labeled
      HL-91 3 h after DMXAA injection showed a dose-dependent increase in tumor levels
      above a threshold of 50 micromol/kg; this same threshold was observed for the
      inhibition of tumor blood flow (determined using Hoechst 33342). DMXAA also
      inhibited blood flow--and increased 99mTc-labeled HL-91 uptake--in MDAH-MCa-4
      mouse mammary carcinomas and in NZMN10 human melanoma xenografts. Whether 99mTc
      labeled HL-91 might also be useful as a biomarker for tumor cell killing was
      investigated by clonogenic assay of surviving cells 15 h after imaging 99mTc
      labeled HL-91 in RIF-1 tumors. Log cell kill in individual tumors showed a
      statistically significant linear correlation (P < 0.001) with 99mTc-labeled HL-91
      uptake after 60 micromol/kg (r2 = 0.79) and 70 micromol/kg (r2 = 0.44) but not at
      80 micromol/kg DMXAA. The lack of correlation at high doses presumably reflects
      the insensitivity of the tumor-averaged 99mTc-labeled HL-91 signal to small
      regions in which tumor blood flow is preserved (which will limit log cell kill).
      The results indicate the potential of 99mTc-labeled HL-91 for the noninvasive
      imaging of tumor blood flow inhibition by antivascular drugs in humans.

PMID- 10969811
TI  - Early deregulation of the the p16ink4a-cyclin D1/cyclin-dependent kinase 4
      retinoblastoma pathway in cell proliferation-driven esophageal tumorigenesis in
      zinc-deficient rats.
AB  - The p16ink4a-cyclin D1/cyclin-dependent kinase 4 (Cdk4)-retinoblastoma (Rb)
      pathway has emerged as a critical target in oncogenesis. The zinc-deficient (ZD),
      N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal cancer model provides a
      tool to study cell proliferation and cell cycle control in cancer initiation.
      Weanling rats were fed a ZD or zinc-sufficient (ZS) diet for 5 weeks, and then
      given a dose of NMBA. After 14 weeks, esophageal tumor incidence was 88% in ZD
      rats with highly proliferative esophagi versus 0% in ZS rats. Expression of
      p16ink4a, cyclin D1, Cdk4, and Rb in relation to that of proliferating cell
      nuclear antigen was characterized in esophagi by immunohistochemistry at 0, 24,
      and 48 h, and 1, 3, 7, 10, and 14 weeks after NMBA treatment. As early as 24 h,
      proliferating cell nuclear antigen-positive focal hyperplastic lesions were
      detected in the suprabasal layers of ZD esophagi. At the same time,
      overexpression of cyclin D1, Cdk4, and Rb was found in the corresponding lesion
      in adjacent esophageal sections. By contrast, p16ink4a expression was reduced or
      absent. At all time points, p16ink4a showed reduced nuclear staining in ZD
      esophagi compared with that in ZS esophagi. In addition, increased expression of
      the hyperphosphorylated forms of Rb was detected in ZD esophagi by
      immunoblotting. Importantly, tumors were consistently observed in ZD esophagi at
      very early time points. These data, obtained using a unique in vivo model for
      esophageal cancer with rapid tumor induction, provide strong evidence for a link
      between deregulation of the p16ink4a-cyclin D1/Cdk4-Rb pathway and the initiation
      of esophageal tumors.

PMID- 10969812
TI  - The N-myc oncogene in human neuroblastoma cells: down-regulation of an
      angiogenesis inhibitor identified as activin A.
AB  - Angiogenesis, the formation of new blood vessels, is seen during embryonic
      development and tumor progression, but the mechanisms have remained unclear.
      Recent data indicate that developmental and tumor angiogenesis can be induced by
      cellular oncogenes, leading to the enhanced activity of molecules stimulating
      angiogenesis. However, activated oncogenes might also facilitate angiogenesis by
      down-regulating endogenous inhibitors of angiogenesis. We report here that
      enhanced expression of the N-myc oncogene in human neuroblastoma cells down
      regulates an inhibitor of endothelial cell proliferation, identified by amino
      acid sequencing as being identical with activin A, a developmentally regulated
      protein. Down-regulation appears to involve interaction of the N-Myc protein with
      the activin A promoter. In addition, activin A inhibits both endothelial cell
      proliferation in vitro and angiogenesis in vivo, and it induces hemorrhage in
      vivo. We suggest that the N-myc-induced down-regulation of activin A could
      contribute to developmental and tumor angiogenesis.

PMID- 10969813
TI  - Mutational and nonmutational activation of p21ras in rat colonic azoxymethane
      induced tumors: effects on mitogen-activated protein kinase, cyclooxygenase-2,
      and cyclin D1.
AB  - Azoxymethane (AOM)-induced colonic carcinogenesis involves a number of mutations,
      including those in the K-ras gene and CTNNB1, that codes for beta-catenin. Prior
      in vitro studies have also demonstrated that wild type p21(K-ras) can be
      activated by epigenetic events. We identified 15 K-ras mutations in 14 of 84 AOM
      induced colonic tumors by three independent methods. By single strand
      conformational polymorphism, we also observed mutations in 22 of 68 tumors in
      exon 3 of CTNNB1. A highly sensitive method was then used to measure p21ras
      activation levels. All tumors assayed possessing K-ras mutations had
      significantly higher p21ras activation levels (8.8 +/- 1.5%; n = 13) compared
      with that of control colon (3.7 +/- 0.4; n = 6; P < 0.05) or tumors without such
      mutations (4.2 +/- 0.4%; n = 70; P < 0.05). Among tumors with wild-type K-ras,
      there was a subset of tumors (18 of 70) that had significantly higher p21ras
      activation levels (8.0 +/- 0.9%; n = 18) compared with control colons. In three
      of four tumors examined with activated wild-type p21ras, we observed increased c
      erbB-2 receptor expression and decreased Ras-GAP expression. In contrast, only
      one of eight tumors examined with wild-type ras and nonactivated p21ras
      demonstrated these alterations. Mitogen-activated protein kinase (MAPK)
      activation and cyclooxygenase-2 (COX-2) expression were increased in tumors with
      mutated or activated wild-type p21ras, compared with their nonactivated
      counterparts. Although beta-catenin mutations did not alter COX-2 expression or
      MAPK activity, mutations in either K-ras or beta-catenin significantly increased
      cyclin D1 expression. In contrast, in tumors with wild-type but activated p21
      ras, cyclin D1 expression was not enhanced. Thus, the spectrum of changes in
      MAPK, COX-2, and cyclin D1 is distinct among tumors with ras or beta-catenin
      mutations or nonmutational activation of p21ras.

PMID- 10969814
TI  - Acidic pH-induced elevation in interleukin 8 expression by human ovarian
      carcinoma cells.
AB  - The expression of interleukin 8 (IL-8) by human ovarian cancer cells correlates
      directly with disease progression, but the exact mechanism of IL-8 induction is
      not clear. The extracellular pH in solid tumors is generally acidic because of
      elevated acid production and impaired clearance of acidic metabolic wastes. We
      determined whether acidic conditions also regulate the expression of IL-8 in
      human ovarian cancer cells. Culturing SKOV3 ip1 ovarian cancer cells in acidic
      medium (pH 6.6) significantly increased IL-8 mRNA (Northern blot) and protein
      (ELISA). The acidosis-mediated transient increase in IL-8 expression involved
      both transcriptional activation of the IL-8 gene and enhanced stability of the IL
      8 mRNA. Detailed functional analysis of the IL-8 promoter revealed that the
      sequence between -133 and -98 bp relative to the transcription initiation site
      was primarily responsible for IL-8 gene transcriptional activation by acidosis.
      Point-mutated luciferase reporter studies indicated that activator protein-1 (AP
      1) and nuclear factor-kappaB (NF-kappaB)-like factor were responsible for acidic
      pH-induced transcriptional activation of the IL-8 gene, and EMSA demonstrated
      that both NF-kappaB and AP-1 bound to these sites on the IL-8 promoter. These
      results indicate that acidic pH activates NF-kappaB and AP-1 in human ovarian
      cancer cells and in doing so increases IL-8 gene expression.

PMID- 10969815
TI  - Evaluation of microsatellite analysis in urine sediment for diagnosis of bladder
      cancer.
AB  - Alterations at microsatellite DNA markers in cells exfoliated in urine have been
      correlated to the presence of bladder cancer. To check the feasibility of such
      noninvasive analysis to routinely diagnose bladder cancers, we have developed a
      highly sensitive method using fluorescent PCR to search for DNA microsatellite
      alterations in urine sediment compared with a blood paired sample. One hundred
      eighty-three patients were included in our study. This population comprised 103
      bladder cancers (64 pTa stages), the complement representing controls and other
      benign or malignant diseases. Results of the analysis at 17 loci in a blinded
      study were compared with cystoscopy and/or pathology. The high reproducibility of
      this technique and the analysis of 26 control patients allowed us to determine
      for each microsatellite a cutoff characterizing a significant allelic imbalance.
      For bladder cancer detection, the overall sensitivity of the test was 84%. Using
      this procedure, we identified alterations in 81%, 84%, 91%, and 100% of pTa, pT1,
      pT2, and >pT2 stages, respectively. This corresponds to 79%, 82%, and 96%
      sensitivity for grades I, II, and III, respectively. Interestingly, for routine
      purposes, we observed an overall sensitivity of 80% (76% for pTa stages) when
      only the eight most rearranged microsatellites were considered. In conclusion,
      the noninvasive feature combined with the rapidity of this fluorescent and highly
      sensitive technique for the detection of early stages provides us with a useful
      help for the diagnosis of bladder cancer.

PMID- 10969816
TI  - The DNA of annexin V-binding apoptotic cells is highly fragmented.
AB  - Jurkat leukemia cells induced to undergo apoptosis by treatment with an antibody
      against the Fas receptor have two annexin V (AV)-binding subpopulations: (a)
      single-positive cells that bind AV but not propidium iodide (PI); and (b) double
      positive cells that bind AV and PI. The single-positive population is thought to
      represent an early stage of apoptosis. We have examined the relationship between
      AV binding and a classical characteristic of apoptosis, DNA fragmentation. Time
      course studies with Jurkat cells treated for 1, 2, or 4 h with anti-Fas indicated
      that the proportion of AV-binding cells was increased after 2 h. A significant
      increase in DNA fragmentation was observed only at 4 h as measured by the mean
      tail moment determined with the alkaline single cell gel electrophoresis (comet)
      assay. This correlation suggests a temporal relationship between the two
      parameters, but does not provide direct evidence of what happens in individual
      cells. We developed a method to measure fluorescent markers of cellular structure
      or function with a laser scanning cytometer and then perform the comet assay on
      the same cells. Cells in each AV-binding subpopulation were re-examined before
      and after electrophoresis. Most AV-/PI- cells had no DNA damage, although a few
      cells showed a pattern of damage characteristic for apoptosis. Double-positive
      cells all had damaged DNA; approximately half had the apoptotic pattern, and the
      rest had a pattern typical for necrosis. Nearly all of the single-positive cells
      had damaged DNA with the apoptotic pattern. Both AV-positive populations
      contained cells with little or no detectable DNA after electrophoresis,
      indicating that the DNA was highly fragmented. These results indicate that AV
      binding is an excellent marker for apoptotic cells, but that these cells already
      have fragmented DNA.

PMID- 10969817
TI  - Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell
      invasiveness and reduce the release of matrix metalloproteinases.
AB  - Eicosanoids modulate the interaction of tumor cells with various host components
      in cancer metastasis. Their synthesis involves the release of arachidonic acid
      (AA) from cellular phospholipids by phospholipase A2 (PLA2), followed by
      metabolism by cyclooxygenases (COXs) and lipooxygenases (LOXs). This study aimed
      to identify the pathway(s) of AA metabolism that are required for the invasion of
      prostate tumor cells. DU-145 and PC-3 human prostate cancer cell lines were used
      to test the effect of inhibitors of PLA2, COX, or LOX on the invasion of prostate
      tumor cells through Matrigel in vitro using the Boyden chamber assay and
      fibroblast-conditioned medium as the chemoattractant. We used nontoxic doses that
      did not inhibit simple cell motility and did not decrease clonogenic survival.
      All of the inhibitors caused a significant reduction in AA release from treated
      cells compared with control cells, which indicated that the treatments were
      biochemically active. Invasion through Matrigel was inhibited by the PLA2
      inhibitor 4-bromophenacyl bromide (4-BPB), the general COX inhibitor ibuprofen
      (IB), and the highly selective COX-2 inhibitor NS398. Inhibition of cell
      invasiveness by 4-BPB (1.0 microM), IB (10.0 microM), and NS398 (10.0 microM) was
      reversed by the addition of prostaglandin E2 (PGE2). PGE2 alone, however, did not
      stimulate invasiveness, which suggests that its production is necessary for
      rendering the cells invasive-permissive but not sufficient for inducing
      invasiveness. In contrast, we found no significant inhibition of invasion of
      prostate tumor cells treated with esculetin (1.0 microM) or nordihydroguiaretic
      acid (1.0 microM), which are specific inhibitors of LOX. We also tested the
      effect of 4-BPB, IB, NS398, and esculetin on the secretion of matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), as
      key enzymes in the proteolysis of Matrigel during invasion, using gelatin
      zymograms and Western blots. Cells that received 4-BPB, IB, or NS398, but not
      esculetin showed a significant reduction in the levels of proMMP-2, MMP-9, and
      proMMP-9 in the culture medium. DU-145 cells did not secrete TIMP-1, and the
      drugs did not alter the secretion of TIMP-2. This work highlights the role played
      by COX in disturbing the balance between MMPs and TIMPs in prostate cancer cells,
      and it points to the potential use of COX inibitors, especially COX-2 selective
      inhibitors, in the prevention and therapy of prostate cancer invasion.

PMID- 10969819
TI  - The effect of exogenous prostaglandin administration on tumor size and yield in
      Min/+ mice.
AB  - This study set out to examine the effect of exogenous prostaglandin (PG)
      administration on tumor development in Min/+ mice. Mice were treated with the
      stable prostaglandin E2 analogue 16,16-dimethyl-PGE2 from 6-18 weeks of age. Mice
      were sacrificed, and tumor burden was assessed using morphometric techniques.
      Parameters measured were median tumor size, mean tumor size, the proportion of
      the area of the gastrointestinal mucosa covered with tumor, and the number of
      tumors per 1000 mm2 of gastrointestinal mucosa. In addition, proliferative and
      apoptotic indices were determined. These measurements were carried out for all
      regions of the small intestine (i.e., duodenum, jejunum, upper ileum, and lower
      ileum) and the large intestine (i.e., cecum and mid-colon/rectum). 16,16-Dimethyl
      PGE2-treated animals showed a significant decrease in tumor burden (by
      approximately 50-70%), in comparison with those animals that were treated with
      vehicle alone (0.001% ethanol in 0.9% sterile saline), in all regions of the
      intestine (at P = 0.008 or better). This effect was contributed to by a reduction
      in the number of tumors (by approximately 20-50%) and a reduction in tumor size
      (by approximately 10-70%). An increase in tumor cell turnover was associated with
      this decrease in tumor burden, as determined by the changes in the levels of
      thymidine incorporation (significant at P = 0.003), apoptosis, and mitosis
      (nonsignificant).

PMID- 10969818
TI  - p53 promotes selection for Fas-mediated apoptotic resistance.
AB  - Although p53 inactivation is implicated as a mechanism to explain diminished
      apoptotic response, it is clear that tumor cells that possess transcriptionally
      functional p53 can also be resistant to diverse apoptotic stimuli. We hypothesize
      that oncogenic activation and DNA damage are sufficient stimuli to increase the
      p53-dependent transcription of Fas and thereby establish a situation in which
      cell to cell contact could be a selective pressure to either lose p53 function or
      inactivate components of the Fas death pathway. Examination of genetically
      matched tumor cell lines that possessed either wild-type or null p53 loci
      indicated that cells possessing functional p53 increased their surface levels of
      Fas and Fas ligand (FasL) in response to DNA damage. In contrast, stress induced
      by changes in the tumor microenvironment such as decreased oxygen did not up
      regulate Fas or FasL. Cells with wild-type p53 underwent Fas-mediated killing in
      the presence of either FasL-expressing killer cells or activating Fas antibodies,
      whereas cells in which p53 was deleted or inactivated were protected from such
      killing. Furthermore, Fas and FasL expression and induction became
      transcriptionally repressed in transformed cells with wild-type p53 with
      increasing passage, whereas other p53 downstream targets and functions, such as
      p21 inducibility and cell cycle arrest, remained intact. Repression of the Fas
      locus could be reverted by treatment with the histone deacetylase inhibitor
      trichostatin A. These results support a model of tumor progression in which
      oncogenic transformation drives tumor cells to lose either p53 or their Fas
      sensitivity as a means of promoting their survival and evade immune surveillance.

PMID- 10969820
TI  - Deregulated manganese superoxide dismutase expression and resistance to oxidative
      injury in p53-deficient cells.
AB  - Loss of function of the tumor suppressor protein p53 represents a very frequent
      event in human carcinogenesis, but the molecular mechanisms linking impaired p53
      activity to increased cell malignancy are still incompletely understood. p53 is
      normally involved in both cell cycle control and the induction of cell death and
      is involved in the latter mainly through the transcriptional regulation of pro-
      and antiapoptotic proteins. Reactive oxygen species are known to be powerful
      inducers of p53 activity; moreover, they play a role in the execution of p53
      dependent apoptosis. Here we show that transformed mouse fibroblasts lacking p53
      are significantly more resistant than wild-type (wt) controls to the cytotoxic
      effect of a number of pro-oxidant treatments. Interestingly, these cells also
      exhibit deregulated expression of the antioxidant enzyme manganese superoxide
      dismutase (MnSOD), a protein known to protect cancer cells from the oxidative
      injury inflicted by antitumoral cytokines and anticancer drugs. MnSOD activity
      was also increased in liver tissue from p53-deficient mice in comparison with wt
      tissue. Transient transfection of wt p53 in HeLa cells led to a significant
      reduction in steady-state MnSOD mRNA levels and enzymatic activity, confirming
      that the expression of this antioxidant enzyme is negatively regulated by p53.
      Forced expression of MnSOD rendered HeLa cells resistant to p53-dependent
      cytotoxic treatments and, in cotransfection experiments, counteracted the growth
      inhibitory effect of p53. Taken together, these data identify MnSOD as a
      potential target for tumor suppressor protein p53 and underscore the relevance of
      MnSOD modulation in the context of normal p53 functions because it is consistent
      with many reports of abnormally increased MnSOD expression in human cancers.

PMID- 10969821
TI  - The need for early predictors of diabetic nephropathy risk: is albumin excretion
      rate sufficient?
AB  - Initial studies showing an approximately 80% rate of progression from
      microalbuminuria (MA) to proteinuria in type 1 diabetic patients led to the broad
      acceptance of MA as a useful clinical predictor of increased diabetic nephropathy
      (DN) risk. Some MA patients, however, have quite advanced renal structural
      changes, and MA may, in these cases, be a marker rather than a predictor of DN.
      More recent studies have observed only about a 30-45% risk of progression of MA
      to proteinuria over 10 years, while about 30% of type 1 diabetic patients with MA
      became normoalbuminuric and the rest remained microalbuminuric. The finding that
      some MA patients have only mild diabetic renal lesions is consistent with the
      lower than originally estimated risk of progression from MA to proteinuria and
      with the notion that some MA patients revert to normoalbuminuria. To increase the
      complexity of the scenario, some normoalbuminuric long-standing type 1 diabetic
      patients have well-established DN lesions and approximately 40% of all patients
      destined to progress to proteinuria are normoalbuminuric at initial screening,
      despite many years of diabetes. A similar picture is emerging in type 2 diabetic
      patients, although fewer studies have been conducted. Thus, the predictive
      precision for MA to progress to overt nephropathy over the subsequent decade or
      so is considerably less than originally described. It is unclear whether this is
      due to changes in the natural history of DN resulting from improved glycemia and
      blood pressure control, or whether there were overestimates of risk in the
      original studies due to the small sample sizes, post hoc analyses, and variable
      MA definitions. Albumin excretion rate (AER) remains the best available
      noninvasive predictor of DN risk and should be regularly measured according to
      established guidelines. However, AER may be unable to define patients who are
      safe from or at risk of DN with an accuracy that is adequate for optimal clinical
      decision making or for the design of certain clinical trials. Investigations into
      new risk markers or into the combined use of several currently available
      predictive parameters are needed.

PMID- 10969822
TI  - Phosphatidylinositol 4,5-bisphosphate and ATP-sensitive potassium channel
      regulation: a word of caution.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) has been suggested to play an
      important role as an endogenous regulator of ATP-sensitive potassium (KATP)
      channels consisting of Kir6.2 as a pore-forming subunit. These studies show the
      ability of PIP2 to activate KATP channel activity and to counteract the
      inhibitory effect of ATP, implying that PIP2 could serve the function of
      modulating the sensitivity of KATP channels to the cytoplasmic free ATP
      concentration. Careful examination of the literature reveals that the definitive
      physiologically relevant experiments to establish efficacy of PIP2 on this
      channel may still have to be performed. Our reservations are based on the
      handling of PIP2 in cell-free experiments and in various strategies designed to
      modulate PIP2 concentrations in intact cells. Furthermore, a potent stimulatory
      effect of phosphatidylinositol 3,4,5trisphosphate, a downstream metabolite of
      PIP2, on KATP channel activity raises the possibility that the effects on the
      KATP channel may not be directly related to PIP2.

PMID- 10969823
TI  - ATP4- mediates closure of pancreatic beta-cell ATP-sensitive potassium channels
      by interaction with 1 of 4 identical sites.
AB  - In pancreatic beta-cells, cytosolic [ATP(4-)] critically controls insulin
      secretion via inhibition of ATP-sensitive potassium (KATP) channels. These
      channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly
      rectifying K+ channel subunit (Kir6.2) plus a regulatory sulfonylurea receptor.
      To elucidate stoichiometry of ATP(4-) action, we analyzed ATP(4-) sensitivity of
      channels coassembled from wild-type Kir6.2 and a loss of ATP(4-) sensitivity
      mutant (G334D). Concentration-inhibition curves for cDNA ratios of 1:1 or 1:10
      resembled those for channel block resulting from interaction with 1 of 4 sites,
      whereas models for inhibition requiring occupation of 2, 3, or 4 sites were
      incongruous. Random assembly of wild-type Kir6.2 with the G334D mutant was
      confirmed by controls, which assessed the effect of an additional mutation that
      induced strong rectification (N160D). We conclude 4 identical noncooperative
      ATP(4-) sites to be grouped within 1 KATP channel complex, with occupation of 1
      site being sufficient to induce channel closure. This architecture might
      facilitate coupling of [ATP(4-)] to insulin secretion and may protect against
      diabetic dysregulation resulting from heterozygous mutations in Kir6.2.

PMID- 10969824
TI  - Molecular mode of inhibition of glycogenolysis in rat liver by the
      dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen
      phosphorylase by an activated metabolite.
AB  - The racemic prodrug BAY R3401 suppresses hepatic glycogenolysis. BAY W1807, the
      active metabolite of BAY R3401, inhibits muscle glycogen phosphorylase a and b.
      We investigated whether BAY R3401 reduces hepatic glycogenolysis by allosteric
      inhibition or by phosphatase-catalyzed inactivation of phosphorylase. In gel
      filtered liver extracts, racemic BAY U6751 (containing active BAY W1807) was
      tested for inhibition of phosphorylase in the glycogenolytic (in which only
      phosphorylase a is active) and glycogen-synthetic (for the evaluation of a:b
      ratios) directions. Phosphorylase inactivation by endogenous phosphatase was also
      studied. In liver extracts, BAY U6751 (0.9-36 micromol/l) inhibited glycogen
      synthesis by phosphorylase b (notwithstanding the inclusion of AMP), but not by
      phosphorylase a. Inhibition of phosphorylase-a-catalyzed glycogenolysis was
      partially relieved by AMP (500 micromol/l). BAY U6751 facilitated phosphorylase-a
      dephosphorylation. Isolated hepatocytes and perfused livers were tested for BAY
      R3401-induced changes in phosphorylase-a:b ratios and glycogenolytic output.
      Though ineffective in extracts, BAY R3401 (0.25 micromol/l-0.5 mmol/l) promoted
      phosphorylase-a dephosphorylation in hepatocytes. In perfused livers exposed to
      dibutyryl cAMP (100 micromol/l) for maximal activation of phosphorylase, BAY
      R3401 (125 micromol/l) inactivated phosphorylase by 63% but glucose output
      dropped by 83%. Inhibition of glycogenolysis suppressed glucose-6-phosphate (G6P)
      levels. Activation of glycogen synthase after phosphorylase inactivation depended
      on the maintenance of G6P levels by supplementing glucose (50 mmol/l). We
      conclude that the metabolites of BAY R3401 suppress hepatic glycogenolysis by
      allosteric inhibition and by the dephosphorylation of phosphorylase a.

PMID- 10969825
TI  - Local factors modulate tissue-specific NEFA utilization: assessment in rats using
      3H-(R)-2-bromopalmitate.
AB  - Insulin-resistant states are associated with accumulation of muscle lipid,
      suggesting an imbalance between lipid uptake and oxidation. We have employed a
      new fatty-acid tracer [9,10-3H]-(R)-2-bromopalmitate (3H-R-BrP) to study
      individual-tissue nonesterified fatty acid (NEFA) uptake in states with
      diminished or enhanced lipid oxidation. 3H-R-BrP was administered to conscious
      male Wistar rats (approximately 300 g) during fasting (5, 18, or 36 h), acute
      blockade of beta-oxidation (etomoxir, 15 micromol/kg), and insulin infusion (0.25
      U x kg(-1) x h(-1)). Estimates of NEFA clearance rates (K(f)*) and absolute rates
      of uptake (R(f)*) were calculated from tissue accumulation of 3H-R-BrP products.
      In the basal state, NEFA uptake was dependent on the oxidative capacity of
      tissues: R(f)* in brown adipose tissue (BAT) > heart (HRT) > diaphragm (DPHM) >
      red quadriceps (RQ) > white quadriceps (WQ) > white adipose tissue (WAT). Fasting
      increased (P < 0.001) K(f)* in WAT but did not change NEFA clearance in other
      tissues. However, plasma NEFA levels were raised (P < 0.01), tending to elevate
      R(f)* in most tissues (P < 0.05: WAT, BAT, WQ, DPHM). Etomoxir reduced (P < 0.01)
      K(f)* only in oxidative tissues (BAT, RQ, DPHM, HRT). Insulin lowered plasma NEFA
      levels (P < 0.001) and significantly decreased R(f)* in most tissues (P < 0.05:
      WAT, RQ, DPHM, HRT). An increased (P < 0.05) clearance was observed in WAT, BAT,
      and WQ; a decrease (P < 0.01) in K(f)* was observed in HRT. This study is the
      first to measure tissue-specific NEFA uptake in conscious rats in the
      postabsorptive, fasted, and insulin-stimulated states. We have demonstrated that
      tissue NEFA utilization is not exclusively determined by systemic availability,
      but that the early steps of NEFA uptake or metabolic sequestration can also be
      rapidly modulated by local processes such as NEFA oxidation.

PMID- 10969826
TI  - Evidence that carotid bodies play an important role in glucoregulation in vivo.
AB  - The carotid bodies are sensitive to glucose in vitro and can be stimulated to
      cause hyperglycemia in vivo. The aim of this study was to determine if the
      carotid bodies are involved in basal glucoregulation or the counterregulatory
      response to an insulin-induced decrement in arterial glucose in vivo. Dogs were
      surgically prepared >16 days before the experiment. The carotid bodies and their
      associated nerves were removed (carotid body resected [CBR]) or left intact
      (Sham), and infusion and sampling catheters were implanted. Removal of carotid
      bodies was verified by the absence of a ventilatory response to NaCN. Experiments
      were performed in 18-h fasted conscious dogs and consisted of a tracer ([3
      3H]glucose) equilibration period (-120 to -40 min), a basal period (-40 to 0
      min), and an insulin infusion (1 mU x kg(-1) x min(-1)) period (0-150 min) during
      which glucose was infused as needed to clamp at mildly hypoglycemic (65 mg/dl) or
      euglycemic (105 mg/dl) levels. Basal (8 microU/ml) and clamp (40 microU/ml)
      insulin levels were similar in both groups. Basal arterial glucagon was reduced
      in CBR compared with Sham (30 + 2 vs. 40 +/- 2 pg/ml) and remained reduced in CBR
      during hypoglycemia (peak levels of 36 +/- 3 vs. 52 +/- 7 pg/ml). Cortisol levels
      were not significantly different between the 2 groups in the basal state, but
      were reduced during the hypoglycemic clamp in CBR. Catecholamine levels were not
      significantly different between the 2 groups in the basal and hypoglycemic
      periods. The glucose infusion rate required to clamp glucose at 65 mg/dl was 2.5
      fold greater in CBR compared with Sham (4.0 +/- 0.4 vs. 1.6 +/- 0.4 mg x kg(-1) x
      min(-1)). Basal endogenous glucose appearance (R(a)) was equal in CBR and Sham
      (2.5 +/- 0.1 vs. 2.5 +/- 0.2 mg x kg(-1) x min(-1)). During the hypoglycemic
      clamp, insulin suppressed R(a) in CBR but not Sham (1.1 +/- 0.2 vs. 2.5 +/- 0.2
      mg x kg(-1) x min(-1) during the last 30 min of the clamp), reflecting impaired
      counterregulation. Glucose disappearance (R(d)) in the basal state was similar in
      CBR and Sham, whereas it was elevated in CBR during the hypoglycemic clamp (4.8
      +/- 0.1 vs. 3.9 +/- 0.1 mg x kg(-1) x min(-1) during the last 30 min of the
      clamp). R(d) was also elevated in euglycemic clamp studies, indicating an effect
      of carotid body resection independent of hypoglycemia. There were no other
      measured systematic endocrine or metabolic effects of carotid body resection
      during euglycemic clamps. In conclusion, we found that the carotid bodies (or
      receptors anatomically close by) play an important role in the insulin-induced
      counterregulatory response to mild hypoglycemia.

PMID- 10969827
TI  - Identification of leptin-induced transcripts in the mouse hypothalamus.
AB  - Long-form leptin receptor (OB-R(L)) is a signal-transducing member of the
      cytokine receptor superfamily that is essential for mediating the effects of
      leptin on mammalian body weight homeostasis. At present, the range of
      transcriptional targets responsive to OB-R(L) activation, and consequently, the
      likely mediators of leptin action, remain undefined. In this report, we have used
      cDNA subtractive hybridization to identify transcripts induced by leptin in
      immortalized hypothalamic neurons expressing OB-R(L). Differential expression of
      the identified transcripts in these cells was confirmed by both array technology
      and Northern blotting. In situ hybridization studies indicate that these
      transcripts are expressed in the mouse central nervous system, including nuclei
      of the hypothalamus that coexpress OB-R(L). Comparative in situ analysis of
      slices of hypothalami generated from control and leptin-injected ob/ob mice
      demonstrates that a subset of the identified transcripts is induced in vivo after
      leptin injection. The potential role of the proteins encoded by these transcripts
      in mediating the effects of leptin on body weight and energy homeostasis are
      discussed.

PMID- 10969828
TI  - Altered cytokine and nitric oxide secretion in vitro by macrophages from diabetic
      type II-like db/db mice.
AB  - Macrophage dysfunction is a likely mechanism underlying common diabetic
      complications such as increased susceptibility to infection, accelerated
      atherosclerosis, and disturbed wound healing. There are no available studies on
      the function of tissue macrophages in diabetes in humans. We have therefore
      studied peritoneal macrophages from diabetic type 2-like db/db mice. We found
      that the release of tumor necrosis factor-alpha and interleukin-1beta from
      lipopolysaccharide plus interferon-gamma-stimulated macrophages and vascular
      endothelial growth factor from both stimulated and nonstimulated macrophages was
      significantly reduced in diabetic animals compared with nondiabetic controls.
      Nitric oxide production from the stimulated db/db macrophages was significantly
      higher than that in the db/+ cultures, whereas there was no difference in their
      ability to generate reactive oxygen species. When studied both at light and
      electron microscopic levels, macrophages in diabetic animals had an altered
      morphological appearance compared with those of normal controls. We conclude that
      the function and morphology of the macrophages are disturbed in db/db mice and
      that this disturbance is related to the mechanisms underlying common inflammatory
      and degenerative manifestations in diabetes.

PMID- 10969829
TI  - Prevention of encephalomyocarditis virus-induced diabetes by live recombinant
      Mycobacterium bovis bacillus Calmette-Guerin in susceptible mice.
AB  - The D variant of encephalomyocarditis (EMC-D) virus causes diabetes in
      susceptible mice by direct cytolysis of pancreatic beta-cells. cDNA covering the
      major outer capsid protein (VP1) of the EMC-D virus was cloned into Mycobacterium
      bovis bacillus Calmette-Guerin (BCG). None of the SJL/J mice immunized with live
      recombinant BCG-VP1 (rBCG-VP1) became diabetic when challenged with the highly
      diabetogenic EMC-D virus, but the control mice inoculated with normal BCG
      developed diabetes during the same challenge. VP1-specific antibodies (including
      neutralizing antibodies) were markedly increased over time and reached the
      maximum titer at week 10 after a single immunization. The plateau of the titer
      lasted longer than 4 weeks. Mice and guinea pigs immunized with live rBCG-VP1
      showed strong delayed-type hypersensitivity to the VP1 of the EMC-D virus. The
      preventive immunity still worked effectively 10 months after the primary
      immunization. At that time, the VP1-specific antibody was almost undetectable in
      the bloodstream, but a large number of VP1-specific lymphocytes was found in the
      spleen of the immunized mice. Our results show that live rBCG-VP1 elicits
      effective humoral and long-lasting cellular immune responses against EMC-D virus
      infection that results in the prevention of virus-induced diabetes in susceptible
      mice.

PMID- 10969830
TI  - The c-Jun amino-terminal kinase pathway is preferentially activated by
      interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells.
AB  - To characterize the differentiation events that selectively target insulin
      producing cells to interleukin (IL)-1beta-induced apoptosis, we studied IL-1beta
      signaling via mitogen-activated protein kinase (MAPK) and stress-activated
      protein kinase in 2 pancreatic endocrine cell lines. We studied the glucagon
      secreting AN-glu cell line and the insulin and the islet amyloid polypeptide
      producing beta-cell line (AN-ins cells), which is derived by stable transfection
      of AN-glu cells with the transcription factor pancreatic duodenal homeobox factor
      1. AN-ins cells were more sensitive to the cytotoxic action of IL-1beta. This
      increased sensitivity was not associated with a more pronounced IL-l-induced
      nitric oxide production in AN-ins cells, but it correlated with a more marked
      activation of the 3 MAPKs extracellular signal-regulated kinases (ERKs)-1/2, c
      Jun NH2-terminal kinase (JNK), and p38 MAPK (p38). This led to increased
      phosphorylation of the transcription factors c-Jun, Elk-1, and ATF2 and of heat
      shock protein 25. Inhibition of ERK-1/2 and p38 did not prevent but aggravated IL
      1beta-induced cell death. In contrast, inhibition of JNK by transfection with the
      dominant negative inhibitor of the JNK-binding domain prevented apoptosis in both
      cell types. Cell death could be elicited by overexpressing the catalytic domain
      of MAPK kinase kinase 1, a specific activator of JNK and nuclear factor-kappaB,
      which does not recruit ERK-1/2 or p38. Coactivation of ERK-1/2 with JNK did not
      prevent apoptosis. In conclusion, increased MAPK signaling in response to IL
      1beta may represent a novel molecular marker of beta-cell differentiation. JNK
      inhibition represents an effective means of preventing IL-1beta-activated beta
      cell destruction.

PMID- 10969831
TI  - The constitutive secretory pathway is a major route for islet amyloid polypeptide
      secretion in neonatal but not adult rat islet cells.
AB  - Islet amyloid polypeptide (IAPP or amylin) is a normal secretory product of the
      pancreatic beta-cell that is cosecreted with insulin and is the major constituent
      of islet amyloid deposits in individuals with type 2 diabetes or insulinomas. We
      have previously reported that glucose stimulates IAPP, but not insulin secretion,
      from neonatal rat beta-cells when regulated secretion is prevented by use of
      calcium-free media, suggesting that IAPP secretion occurs via a constitutive
      secretory pathway. To directly test this hypothesis, we examined the effects of 2
      substances-brefeldin A (BFA) and cycloheximide (CHX)-that are predicted to
      selectively block constitutive secretion on the release of IAPP-like
      immunoreactivity (IAPP-LI) and immunoreactive insulin (IRI) from neonatal rat
      islet cell monolayer cultures. When regulated release was prevented by use of
      calcium-free media, glucose-stimulated IAPP-LI release was nearly abolished by
      blocking constitutive release with 10 microg/ml BFA (mean +/- SD: 8.7 +/- 7.7 vs.
      29.3 +/- 14.3 pmol/l; n = 5; P < 0.05), an inhibitor of constitutive vesicle
      formation. Similarly, calcium-independent, glucose-stimulated IAPP-LI secretion
      was markedly suppressed when new protein synthesis was blocked by administration
      of 20 microg/ml CHX (4.6 +/- 2.1 vs. 29.5 +/- 14.0 pmol/l; n = 5; P < 0.005).
      Secretion of IRI was low in the absence of calcium, and neither BFA nor CHX had
      any further effect. When calcium was added to the incubation media to allow
      regulated secretion of both IRI and IAPP-LI, both BFA (47.7 micro 8.7 vs. 80.7
      micro 10.3 pmol/l; P < 0.001) and CHX (37.3 +/- 5.8 vs. 73.3 +/- 6.2 pmol/l; n =
      5; P < 0.0001) inhibited glucose-stimulated IAPP-LI secretion by approximately
      40%, but again had no inhibitory effect on IRI secretion. These data indicate
      that approximately 40% of glucose-stimulated IAPP-LI release occurs via a
      constitutive secretory pathway in neonatal rat islet cells. By contrast, in adult
      rat islets, glucose-stimulated IAPP-LI release was almost abolished in the
      absence of calcium (86 +/- 3% inhibition; P < 0.05) and unaffected by addition of
      BFA (275 +/- 28 vs. 205 +/- 89 pmol/l; NS) or CHX (160 +/- 20 vs. 205 +/- 89
      pmol/l; NS), suggesting that constitutive secretion of IAPP does not occur in
      mature beta-cells. Collectively, these data suggest that a significant proportion
      of glucose-stimulated IAPP secretion from neonatal, but not adult, rat islet
      cells occurs via a constitutive secretory pathway.

PMID- 10969832
TI  - Glucose uptake, utilization, and signaling in GLUT2-null islets.
AB  - We previously reported that pancreatic islet beta-cells from GLUT2-null mice lost
      the first phase but preserved the second phase of glucose-stimulated insulin
      secretion (GSIS). Furthermore, we showed that the remaining secretory activity
      required glucose uptake and metabolism because it can be blocked by inhibition of
      oxidative phosphorylation. Here, we extend these previous studies by analyzing,
      in GLUT2-null islets, glucose transporter isoforms and glucokinase expression and
      by measuring glucose usage, GSIS, and glucose-stimulated insulin mRNA
      biosynthesis. We show that in the absence of GLUT2, no compensatory expression of
      either GLUT1 or GLUT3 is observed and that glucokinase is expressed at normal
      levels. Glucose usage by isolated islets was increased between 1 and 6 mmol/l
      glucose but was not further increased between 6 and 20 mmol/l glucose. Parallel
      GSIS measurements showed that insulin secretion was not stimulated between 2.8
      and 6 mmol/l glucose but was increased by >4-fold between 6 and 20 mmol/l
      glucose. Stimulation by glucose of total protein and insulin biosynthesis was
      also markedly impaired in the absence of GLUT2. Finally, we re-expressed GLUT2 in
      GLUT2-null beta-cells using recombinant lentiviruses and demonstrated a
      restoration of normal GSIS. Together, these data show that in the absence of
      GLUT2, glucose can still be taken up by beta-cells, albeit at a low rate, and
      that this transport activity is unlikely to be attributed to GLUT1 or GLUT3. This
      uptake activity, however, is limiting for normal glucose utilization and
      signaling to secretion and translation. These data further demonstrate the key
      role of GLUT2 in murine beta-cells for glucose signaling to insulin secretion and
      biosynthesis.

PMID- 10969833
TI  - Transgenic mice with increased hexosamine flux specifically targeted to beta
      cells exhibit hyperinsulinemia and peripheral insulin resistance.
AB  - Hexosamines have been shown to mediate effects of hyperglycemia and so-called
      "glucose toxicity" in insulin-sensitive tissues. To determine the effects of
      hexosamines on insulin synthesis and secretion, transgenic mice were created to
      overexpress the rate-limiting enzyme for hexosamine synthesis, glutamine:fructose
      6-phosphate amidotransferase (GFA), specifically in beta-cells. GFA activity in
      islets of heterozygous transgenic mice was elevated 76% compared with littermate
      controls. The increased GFA activity led to 1.4- and 2.1-fold increased
      pancreatic insulin content in 2- and 10-month-old transgenic mice, respectively
      (P < 0.005). Fasting insulin levels were 1.6-fold higher than in littermate
      controls (P < 0.05). Hyperinsulinemia was evident despite a 28% reduction in
      insulin mRNA levels. The fasting glucose levels in the transgenic mice equaled
      that of controls aged 2-4 months but exceeded that of the controls aged 6-10
      months (means +/- SE 6.9 +/- 0.2 vs. 5.9 +/- 0.2 mmol/l, P < 0.001). By 8 months,
      the males were overweight and mildly diabetic (fasting glucose 8.8 +/- 0.5
      mmol/l) despite persistent hyperinsulinemia. Insulin resistance was confirmed in
      both males and females using the euglycemic-hyperinsulinemic clamp technique;
      glucose disposal rates decreased by 48% in transgenic mice (P < 0.01).
      Triglyceride levels did not differ, and free fatty acid levels were lower in the
      transgenic animals. ATP levels were unchanged in the transgenic islets. We
      conclude that hexosamine biosynthesis is involved in the regulation of insulin
      content in beta-cells by glucose. Increased hexosamine flux in the beta-cell
      results in hyperinsulinemia, insulin resistance, and (in males) mild type 2
      diabetes.

PMID- 10969834
TI  - Tight coupling between electrical activity and exocytosis in mouse glucagon
      secreting alpha-cells.
AB  - alpha-Cells were identified in preparations of dispersed mouse islets by
      immunofluorescence microscopy. A high fraction of alpha-cells correlated with a
      small cell size measured as the average cell diameter (10 microm) and whole-cell
      capacitance (<4 pF). The alpha-cells generated action potentials at a low
      frequency (1 Hz) in the absence of glucose. These action potentials were
      reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The
      action potentials originated from a membrane potential more negative than -50 mV,
      had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp
      experiments revealed the ionic conductances underlying the generation of action
      potentials. alpha-Cells are equipped with a delayed tetraethyl-ammonium-blockable
      outward current (activating at voltages above -20 mV), a large tetrodotoxin
      sensitive Na+ current (above -30 mV; peak current 200 pA at +10 mV), and a small
      Ca2+ current (above -50 mV; peak current 30 pA at +10 mV). The latter flowed
      through omega-conotoxin GVIA (25%)- and nifedipine-sensitive (50%) Ca(2+)
      channels. Mouse alpha-cells contained, on average, 7,300 granules, which undergo
      Ca(2+)-induced exocytosis when the alpha-cell is depolarized. Three functional
      subsets of granules were identified, and the size of the immediately releasable
      pool was estimated as 80 granules, or 1% of the total granule number. The maximal
      rate of exocytosis (1.5 pF/s) was observed 21 ms after the onset of the voltage
      clamp depolarization, which is precisely the duration of Ca(2+)-influx during an
      action potential. Our results suggest that the secretory machinery of the alpha
      cell is optimized for maximal efficiency in the use of Ca2+ for exocytosis.

PMID- 10969835
TI  - Oxygen consumption oscillates in single clonal pancreatic beta-cells (HIT).
AB  - Based on population studies, we have hypothesized that changes in metabolism in
      pancreatic beta-cells precede changes in Ca2+. It is well known from single-cell
      Ca2+ studies that variable oscillatory patterns in Ca2+ occur in response to
      glucose stimulation. The present studies, using the clonal beta-cell line HIT-T
      15, were undertaken to evaluate the relationship between glucose concentration,
      insulin secretion, and O2 consumption and to determine the Ca2+ dependency of
      glucose-induced changes in O2 consumption. In population studies, an excellent
      correlation was found between respiration and insulin secretion, with half
      maximal values at approximately 1 mmol/l glucose for both respiration and
      secretion. In the absence of Ca2+, glucose stimulated O2 consumption but not
      insulin secretion. In single clonal beta-cells, a self-referencing O2 electrode
      was used to assess O2 consumption. Large-amplitude oscillations were found to
      occur in response to stimulation by glucose and were blocked by uncoupling
      respiration with carbonylcyanide p-(trifluoromethoxy)phenylhydrazone (FCCP). They
      were also blocked and respiration totally inhibited by antimycin A, an inhibitor
      of complex III of the respiratory chain. Half of the cells sampled (approximately
      100 total) exhibited increased oscillatory O2 consumption in response to glucose.
      Oscillations in O2 occurred in response to glucose even in the absence of Ca2+,
      and their amplitude increased further on restoration of a normal extracellular
      Ca2+ level. These studies indicated that oscillatory O2 consumption was not
      dependent on Ca2+ but that the amplitude of the O2 oscillations increased in the
      presence of Ca2+, possibly reflecting the additional work involved in insulin
      secretion and Ca2+ pumping. These studies demonstrated, for the first time, a
      direct correlation between O2 consumption and insulin secretion, the oscillatory
      nature of O2 consumption in single cells, and the feasibility of using a highly
      sensitive noninvasive on-line self-referencing O2 electrode to monitor single
      beta-cell respiration.

PMID- 10969837
TI  - Obesity induced by a high-fat diet is associated with reduced brain insulin
      transport in dogs.
AB  - Insulin transported from plasma into the central nervous system (CNS) is
      hypothesized to contribute to the negative feedback regulation of body adiposity.
      Because CNS insulin uptake is likely mediated by insulin receptors, physiological
      interventions that impair insulin action in the periphery might also reduce the
      efficiency of CNS insulin uptake and predispose to weight gain. We hypothesized
      that high-fat feeding, which both reduces insulin sensitivity in peripheral
      tissues and favors weight gain, reduces the efficiency of insulin uptake from
      plasma into the CNS. To test this hypothesis, we estimated parameters for
      cerebrospinal fluid (CSF) insulin uptake and clearance during an intravenous
      insulin infusion using compartmental modeling in 10 dogs before and after 7 weeks
      of high-fat feeding. These parameters, together with 24-h plasma insulin levels
      measured during ad libitum feeding, also permitted estimates of relative CNS
      insulin concentrations. The percent changes of adiposity, body weight, and food
      intake after high-fat feeding were each inversely associated with the percent
      changes of the parameter k1k2, which reflects the efficiency of CNS insulin
      uptake from plasma (r = -0.74, -0.69, -0.63; P = 0.015, 0.03, and 0.05,
      respectively). These findings were supported by a non-model-based calculation of
      CNS insulin uptake: the CSF-to-plasma insulin ratio during the insulin infusion.
      This ratio changed in association with changes of k1k2 (r = 0.84, P = 0.002),
      body weight (r = -0.66, P = 0.04), and relative adiposity (r = -0.72, P = 0.02).
      By comparison, changes in insulin sensitivity, according to minimal model
      analysis, were not associated with changes in k1k2, suggesting that these
      parameters are not regulated in parallel. During high-fat feeding, there was a
      60% reduction of the estimated CNS insulin level (P = 0.04), and this estimate
      was inversely associated with percent changes in body weight (r = -0.71, P =
      0.03). These results demonstrate that increased food intake and weight gain
      during high-fat feeding are associated with and may be causally related to
      reduced insulin delivery into the CNS.

PMID- 10969836
TI  - Identification and functional characterization of the peroxisomal proliferator
      response element in rat GLUT2 promoter.
AB  - We identified the peroxisomal proliferator response element (PPRE) in the +68/+89
      region of the rat GLUT2 gene. To identify whether the putative PPRE in the GLUT2
      gene (GLUT2-PPRE) is functional, GLUT2 promoter-luciferase reporter constructs
      were transfected into CV-1 cells. Promoter activities were increased by
      coexpression of peroxisomal proliferator-activated receptor (PPAR)-gamma,
      retinoid X receptor (RXR)-alpha, and treatment of their ligands; troglitazone and
      9-cis retinoic acid potentiated the transactivational effects. Introduction of
      mutations in GLUT2-PPRE resulted in loss of transactivational effects of the PPAR
      gamma/RXR-alpha heterodimer. Electrophoretic mobility shift assay using nuclear
      extracts of CV-1 cells, which were transfected with various combinations of PPARs
      or RXR-alpha expression plasmids, revealed that heterodimers of PPAR-gamma and
      RXR-alpha preferentially bound to GLUT2-PPRE. In HIT-T15 cells, promoter activity
      of the rat GLUT2 gene was increased by troglitazone and 9-cis retinoic acid, and
      mutations of GLUT2-PPRE resulted in reduction of promoter activity. In addition,
      we observed increased GLUT2 transcription by troglitazone and 9-cis retinoic acid
      in isolated rat primary islets. These results suggested that the GLUT2-PPRE is
      functional and plays a significant role in gene expression of GLUT2 in pancreatic
      beta-cells. This is the first report identifying PPRE in a gene involved in
      glucose homeostasis, linking the effect of troglitazone on the regulation of
      insulin secretion.

PMID- 10969838
TI  - Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and
      develops lipodystrophy in mice.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic
      derivatives of linoleic acid found in beef and dairy products. CLA has been
      reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat
      mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total
      energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis
      revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor
      necrosis factor (TNF)-alpha and uncoupling protein (UCP)-2 mRNA levels increased
      12- and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared
      with control mice. Because it is known that TNF-alpha induces apoptosis of
      adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-alpha mRNA with an
      increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a
      decrease of fat mass, CLA supplementation resulted in a state resembling
      lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of
      white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA
      supplementation decreased blood leptin levels, but continuous leptin infusion
      reversed hyperinsulinemia, indicating that leptin depletion contributes to the
      development of insulin resistance. These results demonstrate that intake of CLA
      reduces adipose tissue by apoptosis and results in lipodystrophy, but
      hyperinsulinemia by CLA can be normalized by leptin administration.

PMID- 10969839
TI  - Effect of hypoglycemia on amino acid and protein metabolism in healthy humans.
AB  - In response to hypoglycemia, healthy individuals rapidly antagonize insulin
      action on glucose and lipid metabolism, but the effects on protein metabolism are
      unclear. Because amino acids are an important substrate for gluconeogenesis and a
      fuel alternative to glucose for oxidation, we evaluated whether hypoglycemia
      antagonizes the hypoaminoacidemic and the antiproteolytic effects of insulin and
      changes the de novo synthesis of glutamine, a gluconeogenic amino acid. To this
      purpose, in 7 healthy subjects, we performed 2 studies, 3.5 h each, at similar
      insulin but different glucose concentrations (i.e., 4.9 +/- 0.1 mmol/l
      [euglycemic clamp] or 2.9 +/- 0.2 mmol/l [hypoglycemic clamp]). As expected,
      hypoglycemia antagonized the insulin suppression of glucose production achieved
      in euglycemia (from 21 +/- 15 to 116 +/- 12% of basal, P < 0.001), the
      stimulation of glucose uptake (from 207 +/- 28 to 103 +/- 7% of basal, P < 0.01)
      and the suppression of circulating free fatty acids (from 30 +/- 5 to 80 +/- 17%
      of basal, P < 0.001). In contrast, hypoglycemia increased the insulin suppression
      of circulating leucine (from 63 +/- 1 to 46 +/- 2% of basal, P < 0.001) and
      phenylalanine (from 79 +/- 3 to 64 +/- 3% of basal, P < 0.001) concentrations.
      Hypoglycemia did not change the insulin suppression of proteolysis (from 79 +/- 2
      to 82 +/- 4% of basal, P < 0.001). However, hypoglycemia doubled the insulin
      suppression of the glutamine concentrations (from 84 +/- 3 to 63 +/- 3% of basal,
      P < 0.01) in the absence of significant changes in the glutamine rate of
      appearance, but it also caused an imbalance between glutamine uptake and release.
      This study demonstrates that successful counterregulation does not affect
      proteolysis. Moreover, it does not increase the availability of circulating amino
      acids by de novo synthesis. In contrast, despite the lower concentration of
      circulating amino acids, hypoglycemia increases the uptake of glutamine that can
      be used for gluconeogenesis and as a fuel alternative to glucose.

PMID- 10969840
TI  - Elimination of glucagon-like peptide 1R signaling does not modify weight gain and
      islet adaptation in mice with combined disruption of leptin and GLP-1 action.
AB  - Leptin and glucagon-like peptide 1 (GLP-1) exhibit opposing actions in the
      endocrine pancreas. GLP-1 stimulates insulin biosynthesis, secretion, and islet
      growth, whereas leptin inhibits glucose-dependent insulin secretion and insulin
      gene transcription. In contrast, GLP-1 and leptin actions overlap in the central
      nervous system, where leptin has been shown to activate GLP-1 circuits that
      inhibit food intake. To determine the physiological importance of GLP-1 receptor
      (GLP-1R)-leptin interactions, we studied islet function and feeding behavior in
      ob/ob:GLP-1R(-/-) mice. Although GLP-1R actions are thought to be essential for
      glucose-dependent insulin secretion, the levels of fasting glucose, glycemic
      excursion after glucose loading, glucose-stimulated insulin, and pancreatic
      insulin RNA content were similar in ob/ob:GLP-1R(+/+) versus ob/ob:GLP-1R(-/-)
      mice. Despite evidence linking GLP-1R signaling to the regulation of islet
      neogenesis and proliferation, ob/ob:GLP-1R(-/-) mice exhibited significantly
      increased islet numbers and area and an increase in the number of large islets
      compared with GLP-1R(+/+) or (-/-) mice (P < -0.01 to 0.05). Similarly, growth
      rates and both shortand long-term control of food intake were comparable in
      ob/ob:GLP-1R(+/+) versus ob/ob:GLP-1R4(-/-) mice. Furthermore, leptin produced a
      similar inhibition of food intake in GLP-1R(-/-), ob/ob:GLP-1R(+/+), and
      ob/ob:GLP1R4(-/-) mice. These findings illustrate that although leptin and GLP-1
      actions overlap in the brain and endocrine pancreas, disruption of GLP-1
      signaling does not modify the response to leptin or the phenotype of leptin
      deficiency in the ob/ob mouse, as assessed by long-term control of body weight or
      the adaptive beta-cell response to insulin resistance in vivo.

PMID- 10969841
TI  - Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE
      stimulated cultured endothelial cells.
AB  - Incubation of bovine aortic endothelial cells (BAECs) with erythrocytes from
      patients with type 2 diabetes induced an increase in endothelin 1 (ET-1)
      production. The effect of erythrocytes on ET-1 synthesis was dependent on
      glycemic control. ET-1 levels after incubation with erythrocytes derived from
      patients with HbA(1c) levels <6% were just half the levels observed after
      incubation with erythrocytes from patients with HbA(1c) levels >8%. Nepsilon
      (carboxymethyl)lysine (CML)-containing protein isolated from patients'
      erythrocytes induced ET-1, and CML-containing protein-dependent ET-1 induction
      was blocked by the recombinant decoy peptide soluble receptor for advanced
      glycation end products (AGEs), which comprises the NH2-terminal Ig domain of the
      receptor for AGEs. In vitro-generated AGEs induced ET-1 mRNA transcription
      (nuclear run-on assay and Northern blot) in a time- and dose-dependent manner.
      Transient transfection of BAECs with a chimeric construct containing the 5'
      promoter region of the ET-1 gene linked to a reporter gene confirmed that AGE
      induced ET-1 promoter activity. Electrophoretic mobility shift assay confirmed
      AGE-inducible binding of members of the nuclear factor-kappab (NF-kappaB) family
      to a potential binding site at -2,090 bp. Binding was functionally significant
      because overexpression of the cytoplasmic inhibitor of NF-kappaB or deletion of
      the NF-kappaB binding site reduced ET-1 induction, whereas overexpression of NF
      kappaB p65 induced ET-1 even in the absence of AGEs. Thus, ET-1 transcription is
      controlled by the AGE-inducible redox-sensitive transcription factor NF-kappaB.

PMID- 10969842
TI  - Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical
      coronary artery disease in men than in women.
AB  - We studied the relationship of coronary artery calcification (CAC), a marker of
      coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD)
      and established cardiovascular disease (CVD) risk factors in a type 1 diabetic
      population. At the 10-year follow-up examination of the Pittsburgh Epidemiology
      of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8
      years) received electron beam tomography (EBT) scanning of the heart and a
      clinical examination. Clinical CAD was defined as a confirmed history of
      myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study
      physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated
      with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in
      men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A
      CACS cut point of 400 was the most efficient coronary calcium correlate of CAD.
      In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In
      logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and
      Beck Depression Inventory independently correlated with prevalent CAD in men and
      overall. Except for CAC, the same variables independently correlated with CAD in
      women, and age also entered the model. CAC was an independent correlate of MI or
      obstructive CAD in both sexes and was the strongest independent correlate in men,
      but CAC was not independently associated with angina and ischemic ECG in either
      sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in
      type 1 diabetes-particularly in men.

PMID- 10969843
TI  - Albuminuria in patients with type 1 diabetes is directly linked to changes in the
      lysosome-mediated degradation of albumin during renal passage.
AB  - Previous studies by our group have shown that albumin is metabolized in rodents
      during renal passage and excreted in the urine as a mixture of intact protein and
      albumin-derived fragments. The aim of this study was to examine whether albumin
      is metabolized during renal passage in nondiabetic volunteers and in type 1
      diabetic patients with varying levels of albuminuria. Nine nondiabetic
      normoalbuminuric volunteers and 11 type 1 diabetic patients with albumin
      excretion rates varying from normoalbuminuria to macroalbuminuria were studied.
      Each subject received an intravenous injection of tritium-labeled albumin ([3H]
      albumin). Urine was collected at 4 h and 24 h after injection and analyzed by
      size exclusion chromatography. The amount of intact and fragmented albumin was
      quantified, and each fraction was analyzed by radioimmunoassay (RIA) for albumin.
      [3H]-albumin in nondiabetic volunteers was metabolized during renal passage to
      small peptide fragments not detectable by conventional RIA (only 0.05-3.8% of the
      total urinary radioactivity was associated with intact albumin). The process
      responsible for albumin fragmentation was similar in diabetic patients with
      normoalbuminuria (intact albumin represented 0.01-4.0% of total urinary
      radioactivity). However, there was a reduction in the fragmentation ratio
      (fragmented:intact) in diabetic patients with micro- or macroalbuminuria (intact
      albumin represented 2.7-55.5%, P = 0.048). This change in the fragmentation ratio
      was directly related to the degree of albuminuria. These results have important
      implications for understanding the mechanisms underlying albuminuria in
      nondiabetic volunteers and type 1 diabetic patients. In nondiabetic volunteers,
      the renal processing of albumin involves a relatively rapid and comprehensive
      degradation of albumin to small fragments (range 1-15 kDa). The degradation
      process is inhibited in diabetic nephropathy in proportion to the level of
      albuminuria detected by RIA.

PMID- 10969844
TI  - Angiotensin II type 1 receptor gene polymorphism and the response to
      hyperglycemia in early type 1 diabetes.
AB  - Recent studies suggest that there is an association between the A1166-->C
      polymorphism of the angiotensin II type 1 receptor (AGT1R), glycemic control, and
      the risk of diabetic nephropathy in subjects with type 1 diabetes. Because
      hypertension and renal hemodynamic function are also related to the risk of
      diabetic nephropathy and because hyperglycemia can activate the renin angiotensin
      system, we sought to determine if there is an association between the AGT1R
      polymorphism, baseline renal and peripheral hemodynamic function, and pressor
      response to high glucose in subjects with early uncomplicated type 1 diabetes.
      There were 39 diabetic subjects genotyped for the AGT1R polymorphism by
      polymerase chain reaction and segregated into 2 groups: those with and those
      without the C1166 allele (AA and AC/CC). The average age was 27 +/- 1 years, and
      the mean duration of diabetes was 3.5 +/- 0.6 years. HbA(1c) values were <10% in
      all subjects and were similar in the 2 groups (8.2 +/- 0.3 vs. 9.1 +/- 0.4%).
      After a 7-day controlled diet (150 mmol sodium, 1.5-2.0 g x kg(-1) x day(-1)
      protein), renal hemodynamic function was assessed by inulin and para
      aminohippurate clearance during clamped euglycemic conditions (4-6 mmol/l). Mean
      values for glomerular filtration rates did not differ between groups during
      euglycemia. In contrast, mean values for renal plasma flow and renal blood flow
      were significantly greater in the AC/CC group compared with the AA group. Values
      for mean arterial pressure were similar in the 2 groups, whereas renal vascular
      resistance was significantly reduced in the AC/CC group. In 20 subjects (10 from
      each genotype subgroup), hemodynamic function was assessed on a second occasion
      during controlled clamped hyperglycemia (9-11 mmol/l) after a similar preparatory
      period. In response to high glucose, plasma renin activity increased in both
      genotype groups to the same extent, but a pressor response was noted only in
      subjects with the C1166 allele. Mean arterial pressure increased significantly in
      the AC/CC subgroup and remained unchanged in the AA subgroup. We conclude that
      there is an association between the AGT1R A1166-->C polymorphism and renal
      hemodynamic function in early type 1 diabetes. But more importantly, the pressor
      response to hyperglycemia is augmented in those diabetic patients with the C1166
      allele and may represent a factor that predisposes them to renal injury during
      periods of inadequate glucose control.

PMID- 10969845
TI  - Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice:
      characterization of a susceptibility locus on chromosome 4 and its relation with
      obesity.
AB  - A backcross model of New Zealand obese mice (NZO) with the lean, atherosclerosis
      resistant SJL strain was established to locate genes responsible for obesity,
      insulin resistance, and type 2 diabetes-like hyperglycemia. In male NZO x F1
      backcross mice, a major susceptibility locus for the development of hyperglycemia
      and hypoinsulinemia (Nidd/SJL) was identified on chromosome 4 between the markers
      D4Mit278 and D4Mit232, 10-28 cM distal of the previously described Nidd1 locus.
      The diabetogenic allele has presumably been contributed by the SJL genome, and it
      appeared to be responsible for approximately 60% of the total prevalence of
      hyperglycemia. The presence of Nidd/SJL did not alter body weight or weight gain
      by week 12. Thereafter, it was associated with reduced weight gain or weight
      loss, presumably as a consequence of decompensated hyperglycemia. In all male
      backcross mice, the prevalence of hyperglycemia at week 22 increased with the
      body weight at week 12, suggesting that the development of hyperglycemia was
      dependent on the degree of obesity. In the absence of Nidd/SJL, mice weighing <50
      g at week 12 did not develop hyperglycemia by week 22. In contrast, in animals
      carrying the diabetogenic allele, the prevalence of hyperglycemia was 20 and 64%
      when the 12-week weight was <45 and 45-50 g, respectively. These data are
      consistent with the conclusion that Nidd/SJL represents a diabetes gene that
      lowers the obesity threshold for the development of hyperglycemia and
      hypoinsulinemia.

PMID- 10969846
TI  - Nonsense mutation of islet-1 gene (Q310X) found in a type 2 diabetic patient with
      a strong family history.
AB  - Islet-1 (Isl-1) is one of the transcription factors that play an important role
      for the formation of the islet cells. We scanned the Isl-1 gene in 77 Japanese
      type 2 diabetic patients with a family history and found a heterozygous nonsense
      mutation (Q310X) in 1 diabetic patient. The mutation was not found in 180
      nondiabetic subjects. This mutation is located in the putative transactivation
      domain and deletes 40 amino acids of the COOH-terminal lesion. The Q310X mutant
      exhibited a 50% reduction in activity compared with the wild-type when tested for
      stimulation of transcription of a human amylin promoter-linked luciferase
      reporter gene in betaTC3 cells. The patient was a 49-year-old nonobese man who
      was diagnosed as having type 2 diabetes at 32 years of age and has been treated
      with sulfonylureas. The mutation was found in his mother, who has type 2
      diabetes, and in his 14-year-old daughter, who has normal glucose tolerance but a
      relatively low insulin response. This is the first reported finding of Isl-1 gene
      mutation in type 2 diabetes. Although Isl-1 is not a common predisposing gene for
      Japanese type 2 diabetes, the mutation in this gene may be a rare cause of
      diabetes in isolated families.

PMID- 10969847
TI  - Association between the human glycoprotein PC-1 gene and elevated glucose and
      insulin levels in a paired-sibling analysis.
AB  - We studied whether there is an association between the single nucleotide
      polymorphism c.533A>C (K121Q) in the glycoprotein PC-1 gene and features of the
      metabolic syndrome in case-control and intrafamily association studies in 922
      subjects from Finland and Sweden. No difference was observed in the Q allele
      frequency between control subjects and type 2 diabetic subjects (12.9 vs. 15.1%).
      The QK genotype was associated with higher fasting plasma glucose (FPG)
      concentrations than the KK genotype in type 2 diabetic patients (P <0.001) and
      their relatives (P <0.05). A permutation test of siblings discordant for the QK
      and KK genotypes also showed that the nondiabetic siblings with the QK genotype
      had higher FPG (6.1 +/- 2.0 vs. 5.4 +/- 0.6 mmo/l, P <0.001) and fasting insulin
      (7.0 +/- 3.6 vs. 4.8 +/- 2.6 mU/l, P <0.05) concentrations than the carriers of
      the KK genotype. In addition, diabetic siblings with the QK genotype had higher
      systolic blood pressure (147.0 +/- 18.0 vs. 140.0 +/- 18.7 mmHg, P <0.05) and
      higher fasting (9.9 +/- 3.0 vs. 8.8 +/- 2.8 mmol/l, P <0.05) and 2-h plasma
      glucose (17.3 +/- 8.5 vs. 12.9 +/- 4.2 mmol/l, P < 0.05) concentrations than the
      diabetic carriers of the KK genotype. The present study shows that, although the
      Q allele of the human glycoprotein PC-1 gene is associated with surrogate
      measures of insulin resistance, it may not be enough to increase the
      susceptibility to type 2 diabetes.

PMID- 10969848
TI  - Heterozygous expansion of the GAA tract of the X25/frataxin gene is associated
      with insulin resistance in humans.
AB  - Friedreich's ataxia (FA) is an autosomal recessive disease that has been
      attributed to a GAA triplet repeat expansion in the first intron of the
      X25/frataxin gene. Impaired glucose tolerance is present in up to 39% of FA
      patients, and clinically apparent diabetes is seen in approximately 18% of the
      affected individuals. Subjects carrying the X25/frataxin GAA repeat in a
      heterozygous state do not develop FA and, therefore, represent an ideal model to
      study the underlying metabolic defects that contribute to the diabetes associated
      with this disorder. In the present study, we have compared 11 first-degree
      relatives of FA patients (i.e., parents or heterozygous siblings of FA patients)
      with matched normal control subjects to study the parameters of glucose
      metabolism. An oral glucose tolerance test revealed diabetes in one of the
      heterozygous subjects who was excluded from further analyses. Using an octreotide
      based quantification of insulin sensitivity, 8 of the remaining 10 study subjects
      showed pronounced insulin resistance, reflecting a significant difference from
      the control group (P = 0.001). In conclusion, a heterozygous expansion of the
      X25/frataxin GAA repeat in healthy individuals is associated with insulin
      resistance and might be considered a genetic co-factor in the pathogenesis of
      mitochondrial subtypes of diabetes.

PMID- 10969849
TI  - The K121Q variant of the human PC-1 gene is not associated with insulin
      resistance or type 2 diabetes among Danish Caucasians.
AB  - The human plasma-cell membrane differentiation antigen-1 (PC-1) has been shown to
      inhibit insulin receptor tyrosine kinase activity. Recently, a K121Q polymorphism
      in the human PC-1 gene was found in a Sicilian population and was shown to be
      strongly associated with insulin resistance. The objectives of the present
      investigation were to examine in the Danish Caucasian population whether the
      K121Q variant was associated with type 2 diabetes or, in glucose-tolerant
      subjects, with impaired whole-body insulin sensitivity. We genotyped 404 Danish
      type 2 diabetic patients and found that the allele frequency of the variant was
      0.14 (95% CI 0.12-0.16), whereas the allele frequency was 0.16 (95% CI 0.13-0.19)
      among 237 matched glucose-tolerant control subjects (P = 0.6). In the control
      subjects, there were no significant differences among wild-type, heterozygous, or
      homozygous subjects in regard to 1) serum insulin and plasma glucose levels at
      fasting, 60 min, or 120 min during an oral glucose tolerance test (OGTT) or 2)
      the estimates of insulin resistance obtained from the homeostasis model
      assessment (HOMA). Furthermore, we investigated the impact of the variant in 2
      other Danish population samples that comprised 356 young healthy subjects and 226
      glucose-tolerant offspring of type 2 diabetic probands, respectively. In all of
      the study populations, the polymorphism was not associated with an altered
      insulin sensitivity index as estimated from an intravenous glucose tolerance test
      in combination with an intravenous injection of tolbutamide. In addition, among
      the 226 offspring, the variations in serum insulin and serum C-peptide responses
      measured during an OGTT were not related to the PC-1 genotype. In conclusion, the
      K121Q polymorphism of the human PC-1 gene is not associated with type 2 diabetes
      or insulin resistance among Danish Caucasians.

PMID- 10969850
TI  - Analysis of the mouse CD30 gene: a candidate for the NOD mouse type 1 diabetes
      locus Idd9.2.
AB  - Members of the tumor necrosis factor receptor superfamily play an important role
      in the initiation, expansion, and termination of an immune response. It has
      recently been demonstrated that one member of this family, CD30, plays a central
      role in maintaining peripheral tolerance by controlling the expansion of
      autoreactive CD8+ T-cells. In the present study, Cd30 was mapped to a 5.6-cM
      interval on chromosome 4 containing the type 1 diabetes susceptibility locus
      Idd9.2. We determined the intron/exon structure of Cd30 and sequenced the exons,
      as well as 1.8 kb of the 5' putative promoter region, from 6 different mouse
      strains. Remarkably, 63 sequence variants, both coding and noncoding, were found.
      A total of 27 sequence variants, 4 of which were nonsynonymous, were found
      between the diabetes susceptible NOD strain and the resistant B10 strain. Of
      these sequence variants, 19 are within the promoter region. However, no
      difference between NOD and the congenic strain NOD.B10 Idd9R1, which has the B10
      allele of Cd30, was observed in CD30 expression at either the mRNA or protein
      level. Given its role in protecting against autoimmunity, one or more of the
      coding variants within CD30 is a good candidate for the Idd9.2 etiological
      variant.

PMID- 10969851
TI  - NIAID will fund HIV vaccine trials network.

PMID- 10969852
TI  - Resources for evaluating the elderly driver.

PMID- 10969853
TI  - Adenocarcinoma arising in endometriosis.

PMID- 10969854
TI  - AMA policy statement on cardiovascular screening of student athletes.

PMID- 10969855
TI  - Maternal serum triple analyte screening in pregnancy.

PMID- 10969856
TI  - Cardiovascular screening of student athletes.
AB  - Each year, a number of children and adolescents die suddenly from cardiac
      problems that are associated with a small subgroup of disorders and high-risk
      behaviors. While sudden cardiac death in any child or adolescent is distressing,
      it can be particularly devastating when it occurs in a seemingly healthy young
      athlete. Although uncommon in competitive sports, sudden death is a catastrophe
      that physicians who care for athletes should attempt to prevent. To prevent the
      occurrence of sudden death or cardiovascular disease progression in young
      athletes, the American Academy of Family Physicians, American Academy of
      Pediatrics, American College of Cardiology, American College of Sports Medicine,
      American Heart Association, American Medical Society for Sports Medicine,
      American Orthopaedic Society for Sports Medicine and American Osteopathic Academy
      of Sports Medicine have developed or endorsed recommendations for cardiovascular
      screening of student athletes as part of a comprehensive sports preparticipation
      physical evaluation (PPE). Knowledge and understanding of these recommendations
      can help physicians make informed decisions about the eligibility of an athlete
      to participate in a particular sport and encourage development of a more uniform
      PPE screening process.

PMID- 10969857
TI  - Depression and sexual desire.
AB  - Decreased libido disproportionately affects patients with depression. The
      relationship between depression and decreased libido may be blurred, but treating
      one condition frequently improves the other. Medications used to treat depression
      may decrease libido and sexual function. Frequently, patients do not volunteer
      problems related to sexuality, and physicians rarely ask about such problems.
      Asking a depressed patient about libido and sexual function and tailoring
      treatment to minimize adverse effects on sexual function can significantly
      increase treatment compliance and improve the quality of the patient's life.

PMID- 10969858
TI  - Polymyalgia rheumatica and temporal arthritis.
AB  - Polymyalgia rheumatica and temporal arteritis are closely related inflammatory
      conditions that affect different cellular targets in genetically predisposed
      persons. Compared with temporal arteritis, polymyalgla rheumatica is much more
      common, affecting one in 200 persons older than 50 years. Temporal arteritis,
      however, is more dangerous and can lead to sudden blindness. The diagnosis of
      polymyalgia rheumatica is based on the presence of a clinical syndrome consisting
      of fever, nonspecific somatic complaints, pain and stiffness in the shoulder and
      pelvic girdles, and an elevated erythrocyte sedimentation rate. Temporal
      arteritis typically presents with many of the same findings as polymyalgia
      rheumatica, but patients also have headaches and tenderness to palpation over the
      involved artery. Arterial biopsy usually confirms the diagnosis of temporal
      arteritis. Early diagnosis and treatment of polymyalgia rheumatica or temporal
      arteritis can dramatically improve patients' lives and return them to previous
      functional status. Corticosteroid therapy provides rapid and dramatic improvement
      of the clinical features of both conditions. Therapy is generally continued for
      six to 24 months. Throughout treatment, clinical condition is assessed
      periodically. Patients are instructed to see their physician immediately if
      symptoms recur or they develop new headache, jaw claudication or visual problems.

PMID- 10969859
TI  - Evaluating the febrile patient with a rash.
AB  - The differential diagnosis for febrile patients with a rash is extensive.
      Diseases that present with fever and rash are usually classified according to the
      morphology of the primary lesion. Rashes can be categorized as maculopapular
      (centrally and peripherally distributed), petechial, diffusely erythematous with
      desquamation, vesiculobullous-pustular and nodular. Potential causes include
      viruses, bacteria, spirochetes, rickettsiae, medications and rheumatologic
      diseases. A thorough history and a careful physical examination are essential to
      making a correct diagnosis. Although laboratory studies can be useful in
      confirming the diagnosis, test results often are not available immediately.
      Because the severity of these illnesses can vary from minor (roseola) to life
      threatening (meningococcemia), the family physician must make prompt management
      decisions regarding empiric therapy. Hospitalization, isolation and antimicrobial
      therapy often must be considered when a patient presents with fever and a rash.

PMID- 10969861
TI  - AUA issues a policy report on PSA monitoring. The American Urological
      Association.

PMID- 10969862
TI  - A dying patient, like me?

PMID- 10969860
TI  - Down syndrome: prenatal risk assessment and diagnosis.
AB  - Down syndrome (trisomy 21) is the most commonly recognized genetic cause of
      mental retardation. The risk of trisomy 21 is directly related to maternal age.
      All forms of prenatal testing for Down syndrome must be voluntary. A nondirective
      approach should be used when presenting patients with options for prenatal
      screening and diagnostic testing. Patients who will be 35 years or older on their
      due date should be offered chorionic villus sampling or second-trimester
      amniocentesis. Women younger than 35 years should be offered maternal serum
      screening at 16 to 18 weeks of gestation. The maternal serum markers used to
      screen for trisomy 21 are alpha-fetoprotein, unconjugated estriol and human
      chorionic gonadotropin. The use of ultrasound to estimate gestational age
      improves the sensitivity and specificity of maternal serum screening.

PMID- 10969863
TI  - Peptides comprising the bulk of rat brain extracts: isolation, amino acid
      sequences and biological activity.
AB  - Chromatographic separation of rat brain extracts followed by automatic Edman
      sequencing of the major individual components resulted in identification of 61
      endogenous peptides derived from known functional proteins (hemoglobin, myelin
      basic protein, cytochrome-c oxidase, etc.) or unknown precursors. The results are
      compared with the data obtained earlier for bovine brain. Although the sequences
      of bovine and rat hemoglobin contain about 20% of amino acid substitutions, the
      families of structurally related peptides are very similar in both extracts.
      Several other proteins also give rise to identical or closely related peptide
      fragments in the two mammalian species. The outlined similarity extends almost
      exclusively to the most abundant peptides present in the extracts. The minor
      components show less overlap. Four hemoglobin-derived peptides isolated from rat
      brain were shown to be biologically active in tumor cells. Eleven are identical
      to bioactive peptides from other species. Ten structurally overlap with bioactive
      peptides from other sources. The data obtained show similar biosynthetic pathways
      of pool components in different species, the resultant peptides being aimed at
      fulfilling related functions.

PMID- 10969864
TI  - Side reactions during photochemical cleavage of an alpha-methyl-6-nitroveratryl
      based photolabile linker.
AB  - The mechanisms of reactions causing irreversible inhibition of the activity of
      enzymes when irradiated in the presence of the recently developed alpha-methyl-6
      nitroveratryl-based photolinker [Holmes CP. J. Org. Chem. 1997; 62: 2370-2380]
      have been investigated. Several experiments based on the interaction of the
      photolinker with model peptides or n-butylamine have been accomplished. A
      complexity of products, resulting from the side reactions competing with the
      'normal' photocleavage of the linker, have been found. The amino and thiol groups
      of the molecules present in the solvents upon irradiation were recognized as
      having a major influence on the course of photolysis. Some of these side products
      resulting from the interaction with amines were identified and the mechanisms by
      which they can be generated are discussed. The mechanism of the interaction of
      the thiol groups present in peptides or proteins with the photolinker is unclear
      and it remains to be further elucidated. It was found that the undesirable
      effects are favored by a basic pH and are largely reduced by a slightly acidic
      pH, together with the presence of dithiothreitol. Significant positive effects of
      dithiothreitol have been observed on the rate as well as the yield of the
      photocleavage. These results demonstrate that the use of photolabile linkers in
      biological media can be accompanied by undesired effects, which can be largely
      reduced by choosing appropriate conditions and additives.

PMID- 10969865
TI  - Enzymatic formation of Glu-Xaa and Asp-Xaa bonds using Glu/Asp-specific
      endopeptidase from Bacillus licheniformis in frozen aqueous systems.
AB  - The capability of Glu/Asp-specific endopeptidase from Bacillus licheniformis to
      form Glu/Asp-Xaa bonds in frozen aqueous systems was investigated. Under frozen
      state conditions, the enzyme was able to catalyse peptide bond formation more
      effectively than in liquid reaction mixtures. The acceptance of amino components
      which were completely inefficient nucleophiles at room temperature indicates a
      changed specificity of Glu/Asp-specific endopeptidase under frozen state
      conditions. Protease-catalysed coupling of two acidic amino acids was
      demonstrated for the first time. The utilization of Glu/Asp-specific
      endopeptidase from Bacillus licheniformis in frozen aqueous systems offers new
      possibilities in enzyme-catalysed peptide synthesis.

PMID- 10969866
TI  - Synthesis of palmitoyl-thioester T-cell epitopes of myelin proteolipid protein
      (PLP). Comparison of two thiol protecting groups (StBu and Mmt) for on-resin
      acylation.
AB  - In order to test the effect of thiopalmitoylation on the encephalitogenic
      properties of two proteolipid protein (PLP) T-cell epitopes, we have studied the
      on-resin S-palmitoylation of peptides, synthesized using the Fmoc/tBu strategy.
      The use of two Cys protecting groups was investigated: the tert-butylsulfenyl
      (StBu) and the methoxytrityl (Mmt). Our studies show that the ease of
      deprotection of the thiol protected with StBu was sequence dependent. The
      deprotection of Cys(StBu) was difficult in the case of the two peptides PLP(104
      117) and PLP(139-151). Neither of the two Cys(StBu) (Cys108 and Cys140,
      respectively) could be deprotected with tributylphosphine. Beta-mercaptoethanol
      was only efficient for the deprotection of Cys(StBu)140 at 85 degrees C and at
      135 degrees C for Cys108. The two palmitoylated peptides could be obtained in
      good yield starting from Cys protected with Mmt. Our conclusion is that the Mmt
      group is the more versatile protecting group of the thiol for use in the on-resin
      synthesis of thiopalmitoylated peptides.

PMID- 10969868
TI  - On the synthesis of orexin A: a novel one-step procedure to obtain peptides with
      two intramolecular disulphide bonds.
AB  - An efficient strategy for the synthesis of orexin A, a recently discovered
      neuropeptide with two intramolecular disulphide bonds, was developed. Four
      different methods for the synthesis of peptides containing two disulphide bonds
      were compared and optimized with respect to reaction time, purity of the crude
      peptide and yield of the purified peptide. A new one-step cyclization method in
      solution is presented for fast, easy and high yield synthesis of orexin A, based
      on iodine oxidation in acetic acid/water and S-acetamidomethyl (S-Acm) and S
      trityl (S-Trt) for side-chain protection of cysteine. Disulphide formation
      without selective side-chain protection leads to the formation of different mono-
      and bicyclic configurations of orexin A. These data stress the requirement of
      selective cysteine side-chain protection in the synthesis of orexin A.

PMID- 10969867
TI  - Conformational consequences of coupling bullous pemphigoid antigenic peptides to
      glutathione-S-transferase and their diagnostic significance.
AB  - Recombinant epitopic peptides BP1 and BP2 representing the Bullous pemphigoid
      autoantigens of BP230 and BP180 bound to the fusion partner glutathione-S
      transferase (pGEX-4T-2, Pharmacia) have been previously shown to increase the
      efficacy of diagnosis of the disease. Using glutathione-S-transferase-bound
      monomer peptides, the sensitivity of the immunological reaction exceeded that of
      the free synthetic epitopes and was further increased with the number of epitopic
      blocks in the multimer fusion products. This has been explained by the avidity
      effect of the fusion partner dimer formation and the high ligand affinity due to
      the tandem repetitions of epitopic sequences. However, a beneficial conformation
      of the bound epitopic peptides might also contribute to the above phenomenon.
      Circular dichroism (CD) and Fourier transform infrared (FTIR) absorption
      spectroscopic studies revealed the importance of glutathione-S-transferase to
      induce and stabilize ordered secondary structures of the epitopic peptides. The
      free monomer and multimer peptides in aqueous buffer were present as a mixture of
      unordered and beta-sheet conformation, while binding them to the fusion partner
      the proportion of ordered secondary structures increased in parallel with the
      number of antigenic epitopes. The most prominent changes in the conformational
      state of the monomers in the fusion form were the increase of alpha-helical and
      beta-sheet and the decrease of unordered conformation, while in the case of
      oligomeric peptides the adoption of a helical conformation was accompanied by the
      decrease of beta-sheet structure. An outstanding alpha-helix content (46%) was
      detected in the case of the trimeric BP1 in its recombinant fusion form.

PMID- 10969869
TI  - Potent cyclic peptide inhibitors of VLA-4 (alpha4beta1 integrin)-mediated cell
      adhesion. Discovery of compounds like cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg)
      (ZD7349) compatible with depot formulation.
AB  - Additional structure-activity relationship studies on potent cyclic peptide
      inhibitors of very late antigen-4 (VLA-4) are reported. The new N- to C-terminal
      cyclic hexa-, hepta- and octapeptide inhibitors like cyclo(MeIle/MePhe-Leu-Asp
      Val-X) (X = 2-4 amino acids containing hydrophobic and/or basic side chains) were
      synthesized using solid phase peptide synthesis methods. The peptides were
      evaluated in in vitro cell adhesion assays and in in vivo inflammation models.
      Many of the peptides like cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg) (ZD7349) (17),
      cyclo(MeIle-Leu-Asp-Val-D-Arg-D-Arg-D-Phe) (20), cyclo(MeIle-Leu-Asp-Val-D-Arg-D
      Arg-MePhe) (21) and cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg-D-Ala-D-Ala) (23) were
      potent inhibitors of VLA-4-mediated cell adhesion and inhibited ovalbumin-induced
      delayed type hypersensitivity (DTH) response in mice. The more potent compounds
      were highly selective and did not affect U937 cell adhesion to fibronectin (VLA
      5), phorbolmyristate acetate or PMA-differentiated U937 cell adhesion to
      intercellular cell adhesion molecule-1 (ICAM-1)-expressing Chinese hamster ovary
      cells (LFA-1) and adenosine diphosphate (ADP)-induced platelet aggregation
      (GPIIb/IIIa). In contrast to the inhibitors like Ac-cyclo(D-Lys-D-Ile-Leu-Asp
      Val) and cyclo(CH2CO-Ile-Leu-Asp-Val-Pip-CH2CO-Ile-Leu-Asp-Val-Pip) described
      earlier, the new compounds were much more compatible with the depot formulations
      based on poly(DL-lactide-co-glycolide) polymers. The hexapeptide cyclo(MePhe-Leu
      Asp-Val-D-Arg-D-Arg) (ZD7349) (17) inhibited MOLT-4 cell adhesion to fibronectin
      and vascular cell adhesion molecule-1 (VCAM-1) with IC50 values of 260 and 330
      nM, respectively, and did not show any significant effect against other integrins
      (IC50 > 300 microM). ZD7349 inhibited ovalbumin-induced DTH response in mice when
      administered continuously using a mini-pump (ED50 0.01 mg/kg/day) or when given
      as an s.c. or i.v. bolus injection at a dose of 1-10 mg/kg. ZD7349 was also
      active in type II collagen-induced arthritis (CIA) and experimental autoimmune
      encephalomyelitis (EAE) tests at a dose of 3-10 mg/kg. The peptide was released
      from some formulations over a period of 10-20 days. ZD7349 is currently
      undergoing pre-clinical investigation.

PMID- 10969870
TI  - Primary structure of fox (Vulpes vulpes) proinsulin based on sequence studies of
      pancreatic peptides and cDNA.
AB  - Insulin and C-peptide were extracted and purified from fox (Vulpes vulpes)
      pancreas using gel filtration, ion-exchange chromatography and HPLC.
      Chromatographic data for the insulin, as well as for its oxidized and
      carboxymethylated chains proved it to be identical to that of polar fox (Alopex
      lagopus) and dog. The sequence analysis of a peptide which was assumed to be the
      corresponding C-peptide revealed that it comprises 23 amino acid residues and is
      identical to the C-peptide fragment isolated from dog pancreas: it differs from
      polar fox C-peptide by a single substitution (Asp-->Glu). mRNA was isolated from
      pancreatic tissue and cDNA was obtained by reverse transcription. A polymerase
      chain reaction was performed using gene-specific primers to obtain a DNA fragment
      corresponding to part of fox proinsulin. DNA sequencing revealed 100% identity to
      dog proinsulin at the protein level, although some amino acids were encoded by
      different codons. The total sequence of proinsulin was deduced from these
      results.

PMID- 10969871
TI  - Partial least squares modeling and genetic algorithm optimization in quantitative
      structure-activity relationships.
AB  - Quantitative structure-activity relationship (QSAR) studies based on chemometric
      techniques are reviewed. Partial least squares (PLS) is introduced as a novel
      robust method to replace classical methods such as multiple linear regression
      (MLR). Advantages of PLS compared to MLR are illustrated with typical
      applications. Genetic algorithm (GA) is a novel optimization technique which can
      be used as a search engine in variable selection. A novel hybrid approach
      comprising GA and PLS for variable selection developed in our group (GAPLS) is
      described. The more advanced method for comparative molecular field analysis
      (CoMFA) modeling called GA-based region selection (GARGS) is described as well.
      Applications of GAPLS and GARGS to QSAR and 3D-QSAR problems are shown with some
      representative examples. GA can be hybridized with nonlinear modeling methods
      such as artificial neural networks (ANN) for providing useful tools in
      chemometric and QSAR.

PMID- 10969872
TI  - A general 13C NMR spectrum predictor using data mining techniques.
AB  - A general-case neural network model for 13C NMR spectrum prediction (estimation)
      was built from more than 8,300 carbon atoms having various environments. Building
      the model from the data set required a few weeks' work using commercial software.
      Average deviation on test data is ca. 4 ppm. There is no limit on molecule
      complexity. Estimation error does not depend on molecule size or complexity. The
      emphasis is on the data, the method and the results, not on the processes that
      take place inside the modelling software. Advantages, disadvantages and
      peculiarities of neural network-based data modelling ("data mining") are
      described at length. The differences in data handling between the data mining
      approach and traditional statistical modelling techniques are discussed and
      illustrated in detail. The spectrum predictor is available from PMSI at no
      charge.

PMID- 10969873
TI  - Predicting the standard enthalpy (deltaH0f) and entropy (S0) of alkanes by
      artificial neural networks.
AB  - Artificial Neural Networks (ANNs) with Extended Delta-Bar-Delta (EDBD) back
      propagation learning algorithm have been developed to predict the standard
      enthalpy and entropy of 87 acyclic alkanes. Molecular weight, boiling point and
      density of the compounds were used as input parameters. The network's
      architecture and parameters were optimized to give maximum performances. The best
      network was a 3-6-2 ANN, and the optimum learning epoch was about 1320. The
      results show that the maximum relative errors of enthalpy and entropy are less
      than 3%. They reveal that the performances of ANNs for predicting the enthalpy
      and entropy of alkanes are satisfying.

PMID- 10969874
TI  - The non-grid technique for modeling 3D QSAR using self-organizing neural network
      (SOM) and PLS analysis: application to steroids and colchicinoids.
AB  - A novel method for modeling 3D QSAR has been developed. The method involves a
      multiple training of a series of self-organizing networks (SOM). The obtained
      networks have been used for processing the data of one reference molecule. A
      scheme for the analysis of such data with the PLS analysis has been proposed and
      tested using the steroids data with corticosteroid binding globulin (CBG)
      affinity. The predictivity of the CBG models measured with the SDEP parameter is
      among the best one reported. Although 3-D QSAR models for colchicinoid series is
      far less predictive, it allows for a discussion on the relative influence of the
      structural motifs of these compounds.

PMID- 10969875
TI  - Polynomial neural network for linear and non-linear model selection in
      quantitative-structure activity relationship studies on the internet.
AB  - This article presents a self-organising multilayered iterative algorithm that
      provides linear and non-linear polynomial regression models thus allowing the
      user to control the number and the power of the terms in the models. The accuracy
      of the algorithm is compared to the partial least squares (PLS) algorithm using
      fourteen data sets in quantitative-structure activity relationship studies. The
      calculated data show that the proposed method is able to select simple models
      characterized by a high prediction ability and thus provides a considerable
      interest in quantitative-structure activity relationship studies. The software is
      developed using client-server protocol (Java and C++ languages) and is available
      for world-wide users on the Web site of the authors.

PMID- 10969876
TI  - Hybrid systems for virtual screening: interest of fuzzy clustering applied to
      olfaction.
AB  - Kohonen neural networks, also known as Self Organizing Map (SOM), offer a useful
      2D representation of the compound distribution inside a large chemical database.
      This distribution results from the compound organization in a molecular diversity
      hyperspace derived from a large set of molecular descriptors. Fuzzy techniques
      based on the "concept of partial truth" reveal to be also a valuable tool for the
      direct exploitation of chemical databases or SOM. In such cases a fuzzy
      clustering algorithm is used. In this paper, a complete hybrid system, combining
      SOM and fuzzy clustering, is applied. As example, a series of olfactory compounds
      was selected. The complexity of such information is that a same compound may
      exhibit different odors. It is shown how fuzzy logic helps to have a better
      understanding of the organization of the compounds. These hybrid systems, using
      simultaneously SOM and fuzzy clustering, are foreseen as powerful tools for
      "virtual pre-screening".

PMID- 10969877
TI  - Structure-toxicity relationships for aliphatic compounds encompassing a variety
      of mechanisms of toxic action to Vibrio fischeri.
AB  - QSARs based upon the logarithm of the octanol-water partition coefficient, log P,
      and energy of the lowest unoccupied molecular orbital, ELUMO were developed to
      model the toxicity of aliphatic compounds to the marine bacterium Vibrio
      fischeri. Statistically robust, hydrophobic-dependent QSARs were found for
      chloroalcohols and haloacetonitriles. Modelling of the toxicity of the haloesters
      and the diones required the use of terms to describe both hydrophobicity and
      electrophilicity. The differences in intercepts, slopes, and fit of these models
      suggest different electrophilic mechanisms occur between classes, as well as
      within the diones and haloesters. In order to model globally the toxicity of
      aliphatic compounds to V. fischeri, all the data determined in this study were
      combined with those determined previously for alkanones, alkanals, and alkenals.
      A highly predictive two-parameter QSAR [pT15 = 0.760(log P) - 0.625(ELUMO) -
      0.466; n = 63, s = 0.462, r2 = 0.846, F = 171, Pr > F = 0.0001] was developed for
      the combined data that models across classes and is independent of mechanisms of
      action. The toxicity of these compounds to V. fischeri compares well to the
      toxicity (50% population growth inhibition) to the ciliate Tetrahymena pyriformis
      (r2 = 0.850).

PMID- 10969878
TI  - Histopathology and polyphenol content in plants infected by phytoplasmas.
AB  - The alterations of cell walls and the localization of several compounds such as
      polyphenols, suberin, lignin, in plum and apple plants infected with plum
      leptonecrosis (PLN) and apple proliferation (AP) phytoplasmas respectively, were
      investigated. Catharanthus roseus plants, infected with AP or PLN were also
      studied. The 4,6-diamidino-2-phenylindole (DAPI) test and transmission electron
      microscopy showed the presence of phytoplasmas in all infected plants. Specific
      histological stainings for cutinized/suberinized cell walls, tannin deposits and
      vacuolar polyphenol inclusions, performed on leaf and stem tissues, revealed an
      increase of these substances in infected plum and apple plants. No differences
      occurred in C. roseus. Total polyphenol analysis confirmed a strong increase (3
      fold) in the polyphenol content in infected tissues, particularly in plum leaves.
      From the data obtained it appears that polyphenols can be considered as defence
      related metabolites in plum and apple plants infected by phytoplasmas. Further
      investigations are necessary to determine whether these compounds play a specific
      role in the development of all phytoplasma/host interactions and in the defence
      related processes.

PMID- 10969879
TI  - 'Glowing' chromosomes in cells undergoing rapid division.
AB  - Previous investigations in which metaphase plates of cells in rapid division were
      incubated in phosphate buffer at high temperature revealed numerous
      heterochromatic dots in chromosomes after Giemsa staining. In contrast,
      chromosomes from cells with a reduced capacity for reproduction were devoid of
      such dots, or the dots were sloughed-off into rings and patches of
      heterochromatin. In two types of cells which were rapidly dividing, namely HeLa
      cells (cervical cancer) and cells from regenerating planaria, phosphate
      incubation followed by Giemsa staining revealed an 'aura' or 'glowing' effect on
      the chromosomes, consisting of a densely staining core surrounded by a lightly
      stained periphery. This finding might be developed into a diagnostic test for
      certain malignancies, for cells undergoing dedifferentiation, or for tissues
      undergoing regeneration.

PMID- 10969880
TI  - Time-dependent changes in superoxide dismutase, catalase, xanthine dehydrogenase
      and oxidase activities in focal cerebral ischaemia.
AB  - Time-dependent changes in the activities of antioxidant enzymes and an oxidant
      enzyme, xanthine oxidase (XO), were detected in primary and peri-ischaemic brain
      regions during permanent occlusion of the middle cerebral artery (MCAO) in rats.
      There were no changes in superoxide dismutase (SOD) and catalase (CAT) activities
      after 3 h of MCAO, whereas antioxidant enzyme activities decreased significantly
      in ischaemic brain areas following 24 h of ischaemia. After 48 h, the enzyme
      activities returned to the baseline but then a further increase was observed in
      ischaemic brain areas by 72 h post-ischaemia. Normally, XO exists as a
      dehydrogenase (XD), but it is converted to XO which contributes to injury in some
      ischaemic tissues. The XO activity increased slightly at 3 h after ischaemia, but
      after 24 h of ischaemia it returned to the baseline and then remained relatively
      unchanged in ischaemic areas. Pretreatment with allopurinol before ischaemia
      prevented changes in SOD and CAT activities and attenuated brain oedema during 24
      h of ischaemia. Neither XO nor XD activity changed in allopurinol-treated rats at
      the times of ischaemia. These results indicated that ischaemic brain tissue
      remained vulnerable to free radical damage for as long as 48 h after ischaemia,
      and XO was probably not an important source of free radicals in cerebral
      ischaemia.

PMID- 10969881
TI  - Morphometric changes associated with sex and development in the Malpighian
      tubules of Aedes aegypti.
AB  - The Malpighian tubules of Aedes aegypti showed significant differences in their
      diameters between male and female larvae, male and female pupae, male larvae and
      male adults and male pupae and male adults. In every case, female values were
      greater than in males. Measurements of mean nuclear areas of the principal and
      stellate cells from Malpighian tubules, taken in males and females during
      development, showed that this parameter in both types of cell was significantly
      greater in females than in male larvae, pupae and adult stages. In males,
      significant differences between developmental stages were observed only in
      comparison with the nuclear area of larvae and adults in the principal cells, but
      in females, every comparison between stages showed significant differences except
      between pupae and adults in stellate cells. The frequency distribution of nuclear
      area values, in development, for male stellate and principal cells, were mostly
      concentrated in the first seven classes among the 30 classes considered in every
      stage, while for females, the frequency dropped drastically in the same classes
      from larvae to pupae and adults, moving to classes of higher values. Considering
      the importance of Malpighian tubules in insect physiology, the meaning of the
      differences detected are discussed on the basis of different metabolic levels,
      between sexes and developmental stages.

PMID- 10969882
TI  - Peptide YY administration decreases brain aluminum in the Ts65Dn Down syndrome
      mouse model.
AB  - We have previously reported the Ts65Dn (Ts) mouse has impaired intestinal
      absorptive function and amino acid metabolism. Peptide YY (PYY) has enhanced
      glucose absorption in mice and turkeys. Other studies have reported that persons
      with Down syndrome have increased intestinal absorption of aluminum. Alzheimer's
      like lesions have been reported in Ts mice. Trial 1 of this study examined brain
      Al concentrations, plasma metabolites and intestinal metabolism of 40 control and
      40 Ts mice administered 300microg PYY/kg body weight or 0.9% saline for 3d. Trial
      2 examined nutrient digestibility of 12 C and 12 Ts given PYY or saline for 14d.
      In Trial 1, PYY lowered (p<0.05) the brain Al pool (mg/g FBW) in both C and Ts
      mice by 80% compared to saline. Ts mice had increased plasma NH3 (329 vs. 269
      microM, p<0.05), decreased plasma glucose (7.4 vs. 8.4 mM, p<0.01), elevated
      apparent energetic efficiency of jejunal glucose uptake (p<0.01) and elevated
      brain Al pool (0.41 vs. 0.12 microg, p=0.06) compared to C mice. In Trial 2, PYY
      increased small intestinal density (mg/cm) 12% in both genotypes (p<0.05), but
      did not alter nutrient digestibility. Brain Al accretion and hyperammonemia are
      proposed risk factors for Alzheimer's disease (AD). Ts mice and PYY appear to be
      suitable models for the study of metabolic and neurological anomalies in Down
      syndrome and AD.

PMID- 10969883
TI  - Effects of the high growth (hg) mutation on reproduction in high growth (HG)
      female mice.
AB  - Reproductive performance was characterized in females of a line of mice
      homozygous for a recessive mutation with a major effect on growth, the high
      growth (hg) mutation. Specifically, the age at onset of puberty, length of the
      estrous cycle, ovulation rate, and gestation length in high growth (HG) mice were
      determined and compared with control mice. HG females reached puberty at an age
      similar to control animals, exhibited normal ovulation rates and estrous cycle
      length, but had a shorter length of estrus. Number of fetuses at Day 17 of
      gestation was greater and gestation length was longer in HG females. The HG
      females exhibited a variety of reproductive disorders, including increased
      incidence of repeated detection of mating plugs without intervening pregnancy
      ("replug"), increased incidence of repeated detection of mating plugs within an
      interval of 1-8 days without intervening pregnancy ("recycle"), increased
      interval between pairing with a male and detection of the first mating plug,
      increased interval between mating and conception, increased postnatal mortality,
      decreased litter size, and increased incidence of vaginal septum.

PMID- 10969884
TI  - A multiphasic approach for describing serial height data of Fels children: a
      hexaphasic-logistic-additive growth model.
AB  - In this paper, we reported the results obtained from fitting a new growth model
      to serial height data of 80 Fels children. The model assumed that human height
      growth curves are due to the combined effects of six macroscopic logistic growth
      processes, each reaching the same asymptotic height value. It was named the
      Walker and Walker-Hexaphasic-Logistic-Additive (WWHLA) growth model. An advantage
      to using this model is that it allowed us to easily fit entire growth curves with
      14 biologically interpretable parameters. We tested the model using a
      computerized nonlinear least squares technique. The results showed that the new
      model worked extremely well. The fits resulted in high R, R2, and adjusted R2
      values, large F values, relatively low residual mean squares, Durbin-Watson
      statistics that were very close to 2, and relatively small standard error
      estimates for the model parameters. In addition, the normality and constant
      variance test passed for more than 95 percent of the children, and the graphs of
      the residuals essentially showed no model bias. The new model identified the six
      growth components or processes in both male and female growth curves. The
      processes were named according to when they reached their peak height velocity:
      neonatal, infantile, early-childhood, middle-childhood, late-childhood, and
      pubertal. Preliminary results suggest that the WWHLA model appears to be the best
      that is currently available at this time for describing the human growth curve.

PMID- 10969885
TI  - Expression of insulin-like growth factor binding proteins (IGFBPs) before and
      during the hormone sensitive period of adipose tissue development in the fetal
      pig.
AB  - The present study examined the influence of fetal age and thyroxine (T4) and
      growth hormone (GH) treatment, on the expression of insulin-like growth factor
      binding proteins (IGFBPs) in fetal pigs. On day 70 of gestation fetuses were
      either hypophysectomized (hypox), hypox and implanted with T4 pellets, or left
      intact, and were recovered 5, 10, 15 and 20 days following hypox and T4 pellet
      placement. Intact fetuses were also recovered from several dams at 50 days of
      gestation. In additional dams, hypox fetuses (day 70) were implanted with GH
      loaded Alzet mini-pumps on day 90, and control, untreated, and GH-treated hypox
      fetuses were recovered on day 105 of development. Subcutaneous adipose tissue,
      serum and other fetal tissues were collected at the time of recovery and prepared
      for subsequent ligand blot analysis with 125I -IGF-1 and immunoblot analysis with
      IGFBP antibodies. The main effect of IGFBP was significant (P <0.01) for age
      associated changes in serum IGFBP percentages. Between 50 and 75 days of fetal
      development the levels of 29 kDa IGFBPs in adipose tissue and serum markedly
      increased. In contrast, IGFBP-2 levels decreased and IGFBP-4 levels increased in
      adipose tissue while IGFBP-2 levels increased and levels of IGFBP-4 and -3
      decreased in serum. Fetal hypox decreased adipose tissue IGFBP levels in a time
      and IGFBP-dependent manner. For instance, IGFBP-2 and 29 kDa IGFBP levels
      decreased much faster after fetal hypox than did IGFBP-3 levels whereas IGFBP-4
      levels did not decrease. The main effect of IGFBP was significant (P<0.01) for T4
      induced changes in adipose tissue IGFBP levels. T4 treatment increased adipose
      tissue levels of 29 kDa IGFBPs but did not influence IGFBP-2,-3 and -4 levels. GH
      treatment had no influence on adipose tissue or serum IGFBP levels. These studies
      indicate that IGFBP-1 (one of the 29 kDa IGFBPs) may be the major IGFBP mediator
      of the influence of T4 on fetal development.

PMID- 10969886
TI  - Recovery of memory function following traumatic brain injury in pre-school
      children.
AB  - Traumatic brain injury (TBI) may have a profound impact on a child's ongoing
      development. Various risk factors have been found to predict outcome, but
      considerable variability remains unexplained. This study used a prospective,
      longitudinal design to examine recovery of memory function following TBI within
      the pre school period. Ninety-six children with TBI were divided according to
      injury severity (mild, moderate, severe), and compared to age and SES matched
      healthy controls (n = 35). Children were evaluated acutely and at 6,12 and 18
      months post-injury using intellectual and memory measures. Results showed a
      relationship between greater injury severity and poorer intellectual ability.
      This dose-response relationship was not clearly evident for memory function
      within the acute phase of recovery, but developed over time, with greater memory
      impairments evident for children with more severe TBI by 12 months post-injury.
      Children with mild TBI exhibited few memory problems. Findings are discussed in
      the context of theories of plasticity and recovery of function.

PMID- 10969887
TI  - Assessing subtle memory impairments in the everyday memory performance of brain
      injured people: exploring the potential of the extended Rivermead Behavioural
      Memory Test.
AB  - A substantial number of brain injured patients complain of memory deficits,
      despite achieving scores within the normal range on tests of memory functioning.
      The Rivermead Behavioural Memory Test is an ecologically valid test used to
      assess everyday memory problems. This test is effective at detecting moderate to
      severe impairments, yet subtle memory deficits may go undetected for some
      patients who achieve a score within the normal range. The initial development of
      an extended version of this test (RBMT-E), designed to detect subtle decrements
      in memory performance, has recently been described. The performance of 16 brain
      injured patients was assessed on both the RBMT and the KBMT-E. The performance of
      these patients on the RBMT-E was compared with that of matched controls. Overall,
      the patients performed significantly worse than the controls, and showed
      particular difficulty in two subtests involving recalling a route and remembering
      to deliver a message. Those patients who scored in the 'normal' range on the RBMT
      could be further differentiated on the basis of their RBMT-E scores into 'good',
      'average' and 'poor' performance categories. The patients' performance was not
      significantly associated with general intellectual ability. These results suggest
      that the RBMT-E may be a useful clinical tool to aid therapists in the assessment
      of subtle impairments of everyday memory performance following brain injury.

PMID- 10969888
TI  - Neuropsychological predictors of distress following traumatic brain injury.
AB  - Emotional and behavioural difficulties are one of the most common difficulties
      following traumatic brain injury (TBI), although it is not clear which
      individuals with TBI become most distressed. Numerous factors contribute to
      adjustment following TBI, and the current study examined degree of cognitive
      decline as one potential contributor to distress following TBI. The relationship
      between cognitive functioning and distress may be conceptualized as being related
      to (a) an individual's absolute level of cognitive ability following TBI, or (b)
      relative degree of decline following TBI (i.e. the greater the decline, the
      greater the distress, regardless of absolute level of ability). The current study
      tested these hypotheses by comparing a measure of global emotional distress with
      measures of absolute level of neuropsychological functioning and indices of
      cognitive decline. In contrast to hypotheses, regression analyses indicated that
      estimated pre-morbid ability accounted for more variance in distress following
      TBI than either absolute level of functioning or indices of cognitive decline,
      with individuals with higher estimated pre-morbid abilities reporting lower
      levels of distress. Treatment implications are discussed.

PMID- 10969889
TI  - Functional outcome for African Americans and Hispanics treated at a traumatic
      brain injury model systems centre.
AB  - OBJECTIVE: To describe the demographics, incidence and functional outcome for
      African Americans and Hispanics treated at a traumatic brain injury (TBI) model
      systems centre. DESIGN: Retrospective data analysis of patients admitted to an
      acute inpatient rehabilitation national TBI model systems centre. SETTING: A
      tertiary care university medical centre participating in the NIDRR Traumatic
      Brain Injury Model Systems project. SUBJECTS: Eighty-seven patients with TBI
      admitted to a Model Systems acute intensive interdisciplinary rehabilitation
      setting between 1989-1999. Information was extracted from the National TBI Model
      Systems data base for demographics such as age, race, education, gender, marital
      and employment status, sponsorship, injury aetiology and severity. OUTCOME
      MEASURES: Functional outcome was determined using the Functional Independence
      Measure (FIM), and the Disability Rating Scale (DRS) at the time of admission and
      discharge. RESULTS: Descriptive statistics were completed using SPSS. African
      American (94.3%) and Hispanic (5.7%) patients were injured most often as a result
      of motor vehicle accidents (48.8%). Males comprised 86.2% of this population,
      which had an average age of 34.5 years (SD = 13.1). On admission, average GCS
      score was 7.8 (SD = 3.6), average DRS was 13.5 (SD = 5.8), and average FIM total
      score was 49.8 (SD = 26.5). Average length of unconsciousness was 5.2 days (SD =
      27.9), while average length of post-traumatic amnesia was 41.9 days (SD = 59.3).
      At the time of injury, 78.2% of the patients were not married. The majority of
      patients (97.7%) had private residences and 88.5% returned to their original
      home. Most patients had at least a high school education or passed a high school
      equivalent exam (49.4%) and were employed (70.1%) at the time of injury. Only 7%
      of the patients had a history of prior TBI. With regard to substance use, only
      34.2% of patients reported pre-morbid illicit drug use. However, 50.5% met
      criteria for heavy or moderate alcohol use rates. Only 35.6% of patients reported
      a pre-morbid history of arrests, with the average number of arrests equal to 4.5
      (SD = 10.2). Within this population, the number of drug or alcohol related
      arrests was 4.8 (SD = 13.5). CONCLUSIONS: Unmarried African American males, with
      an average age of 35 years, predominated at this institution. The primary
      mechanism of injury was motor vehicle accidents. The majority of patients had, at
      least, a high school education or passed an equivalency exam, were employed at
      the time of their injury and were discharged to their prior private residence.
      While half of the patients met criteria for moderate-to-heavy alcohol
      consumption, only one-third of the patients reported a history of pre-morbid
      illicit drug use. This descriptive analysis supports the need for further
      investigation of minority populations that sustain TBI and will enhance the
      accuracy of implications that minority status may have on functional outcome.

PMID- 10969890
TI  - Neuropsychological assessment and the Disability Rating Scale (DRS): a concurrent
      validity study.
AB  - Assessment of current level of functioning among clients with traumatic brain
      injury (TBI) often guides the establishment of realistic outcome goals for post
      acute rehabilitation. Further, data generated from neuropsychological testing
      provide a clinician with a better understanding of a client's pattern of
      cognitive strengths and weaknesses. The Disability Rating Scale (DRS) is commonly
      used by TBI rehabilitation facilities to assess a client's general level of
      functioning in terms of impairment, disability, and handicap. Previous studies
      have used clients' neuropsychological test results to predict future level of
      functioning. These studies have shown mixed results regarding the predictive
      validity of the test findings; however, they usually employ only a limited number
      of tests for prediction representing a limited number of cognitive domains. Using
      a concurrent validity design, the present study investigated the bivariate
      associations between various neuropsychological testing domains (i.e.
      intellectual, academic, language, visuoperceptual, memory, and executive
      functioning) and level of functioning as indexed by the DRS. Participants were
      administered the DRS and the neuropsychological evaluation during the initial
      part of post-acute rehabilitation. Composite scores were derived for each of the
      neuropsychological domains. Most participants were categorized as sustaining a
      severe TBI. The mean age and education of this predominately male sample was
      28.84 years (SD = 9.13) and 11.83 years (SD = 1.7), respectively. Results
      revealed a significant positive relationship between performances in
      intellectual, executive, academic, and visuoperceptual domains and level of
      functioning.

PMID- 10969891
TI  - Secondary traumatization among wives of PTSD and post-concussion casualties:
      distress, caregiver burden and psychological separation.
AB  - This study has two aims. First, it assesses the implication of husbands' post
      traumatic stress disorder (PTSD) and post-concussion syndrome (PC) on their
      wives' sense of burden and emotional distress. The second aim was to examine the
      implication of the women's separation-individuation on their adjustment. Sixty
      women participated in study: 20 women married to war veterans diagnosed as
      suffering to PTSD, 20 women married to war veterans suffering from PC, and 20
      women married to healthy controls. Data was collected using self report
      questionnaires assessing psychiatric symptomatology, caregiver burden and
      psychological separation-individuation. Results indicate that women from both
      research groups suffer from higher levels of burden and distress than controls.
      The level of separation-individuation was found to be correlated to levels of
      burden and distress. The complex implications of living with a traumatized spouse
      are discussed.

PMID- 10969892
TI  - Coping and stress in Canadian family caregivers of persons with traumatic brain
      injuries.
AB  - The purpose of this study was to document the stresses reported by Canadian
      caregivers of persons with brain injuries and to consider the factors which serve
      to mediate or moderate such stress. Highest stress scores on the Holroyd
      Questionnaire on Resources and Stress-Short Form (QRS) were associated with
      Lifespan Care and Personal Burden. Although overall burden as reported on the QRS
      by parents and spouses did not differ from other studies, it did differ somewhat
      for specific types of burden. Social Support and Spiritual Support, as measured
      by the F-COPES, fell within the medium use category, and scores for Reframing,
      Mobilizing and Passive Appraisal fell within the high use category. In multiple
      regression analyses, client competency as measured by the Patient Competency
      Rating Scale emerged as a major predictor of stress associated with Cognitive
      Impairment, Physical Limitations, Lifespan Care, Terminal Illness Stress, Limits
      on Family Opportunities, and Personal Burden. In contrast, other client
      characteristics (e.g. Time Since Injury) accounted for relatively little
      variance. The results also indicate that both Refraining and Seeking Spiritual
      Support as coping strategies can make an important contribution to stress
      reduction.

PMID- 10969893
TI  - Outcome following traumatic brain injury in the elderly: a critical review.
AB  - BACKGROUND: The elderly are at risk for traumatic brain injury (TBI), but their
      outcome following these injuries remains unclear. OBJECTIVE: This paper
      critically reviews research done to date on cognitive and functional outcome
      following TBI in the elderly. METHODS: MEDLINE and PSYCHLIT databases going back
      to 1965 were searched. RESULTS: Studies suggest that TBI results in adverse
      cognitive and functional outcomes in the elderly. There is uncertainty as to
      whether TBI is a significant risk factor for Alzheimer's disease (AD).
      Methodological problems in these studies include selection bias, small samples,
      retrospective analyses, and, particularly, the failure to address the role of pre
      morbid functioning. These problems limit the strength of the outcome studies, and
      may account for the equivocal findings on AD risk. CONCLUSIONS: It is premature
      to conclude from the published research to date that the elderly have a uniformly
      poor outcome following TBI. Directions for further research are suggested.

PMID- 10969894
TI  - Depressive state and silent vascular brain lesions.

PMID- 10969895
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) characteristics in Japan: variety of clinical
      features.

PMID- 10969896
TI  - Pulmonary lymphangiomyomatosis--past, present, and future.

PMID- 10969897
TI  - Rheumatic manifestations in paraneoplastic syndrome.

PMID- 10969898
TI  - Acute glomerulonephritis.
AB  - Acute glomerulonephritis (AGN) is a representative disease of acute nephritic
      syndrome characterized by the sudden appearance of edema, hematuria, proteinuria,
      and hypertension. The prototype of AGN is acute poststreptococcal
      glomerulonephritis (APSGN). "Nephritogenic streptococci" are defined as organisms
      that are cultured from a patient who develops AGN. Although only a limited number
      of M-types of streptococci have been recognized as "nephritogenic streptococci",
      all M-types of streptococci may have nephritogenic potential because the genes
      for major putative nephritogenic antigens such as SPEB and NAPIr are found to be
      present in all group A streptococci thus far examined. Pathogenic mechanisms for
      APSGN involving both humoral and cell-mediated immunity have been recently
      proposed. The role of humoral immunity is presumed to be mediated by the in situ
      formation of nephritogenic streptococcal antigen-antibody complexes and
      circulating immune complexes. While in the cellular immune component a role for
      delayed-type hypersensitivity has been suggested to contribute to the
      pathogenesis of APSGN.

PMID- 10969899
TI  - Strongyloidiasis--progress in diagnosis and treatment.
AB  - Strongyloidiasis is an intestinal parasitic disease caused by Strongyloides
      stercoralis. Basically, detecting larvae of S. stercoralis in feces makes
      definitive diagnosis. The ordinary agar plate culture method developed at our
      department is much simpler to handle and much more sensitive than the
      conventional filter paper culture method. It is considered to be the most useful
      method in the diagnosis of strongyloidiasis and in evaluation of the eradicating
      effect. Among chemotherapeutic agents, thiabendazole representing the
      benzimidazole compounds is most effective. However, it has a problem in safety,
      since its adverse effects and liver dysfunction occur with a high incidence, and
      it can be severe. Regarding the effects of mebendazole, albendazole and
      ivermectin, a study was conducted which included many patients. A high incidence
      of liver dysfunction was observed with mebendazole, and eradicating effect was
      not sufficient with albendazole. Ivermectin is different from benzimidazole
      compounds in a pharmacokinetic profile. However, ivermectin showed a strong
      anthelmintic effect with the least toxicity. We therefore consider ivermectin is
      the most useful drug for the treatment of strongyloidiasis.

PMID- 10969900
TI  - Accuracy of detection of colorectal neoplasia using an immunochemical occult
      blood test in symptomatic referred patients: comparison of retrospective and
      prospective studies.
AB  - OBJECTIVE: In this study the sensitivity and specificity of immunochemical tests
      for colorectal neoplasia were evaluated in retrospective and prospective studies.
      METHODS: Four types of fecal blood tests--a chemical test (Hemoccult II) and
      three different immunochemical tests including a test which detects hemoglobin
      and transferrin- were performed in the retrospective study. In the prospective
      study the test for hemoglobin and transferrin was used for all patients that
      underwent total colonoscopy. PATIENTS: One hundred seven patients with colorectal
      neoplasia, 57 with gastroduodenal bleeding, and 62 with normal digestive tracts
      were examined retrospectively. One thousand two hundred and ninety-eight
      nonspecifically symptomatic patients whose endoscopic examination was negative
      for hemorrhagic lesions in the upper digestive tract were examined prospectively.
      RESULTS: In the retrospective study, sensitivities for the detection of
      colorectal cancers and adenomas with diameters > or =10 mm using the tests which
      detect hemoglobin and transferrin were 98% and 89%, respectively. These were the
      highest sensitivity among the four tests. The specificity of this test was 97%,
      which was higher than that of the Hemoccult II test. In the prospective study,
      the sensitivities of the tests for hemoglobin and transferrin for the detection
      of colorectal cancers and adenomas with diameters > or =10 mm were 79% and 33%,
      respectively. The specificity was 95%. CONCLUSIONS: The test for hemoglobin and
      transferrin showed the highest sensitivity and specificity for colorectal
      neoplasia in the retrospective study. The sensitivity and specificity of this
      test were not so high in the prospective study, but they may be clinically
      applicable in the evaluation of patients with various nonspecific symptoms.

PMID- 10969901
TI  - Long-term results of inferior vena cava filters: experiences in a Japanese
      population.
AB  - OBJECTIVE: In this prospective, non-controlled observational study, we evaluated
      the middle- to long-term results of placement of inferior vena cava (IVC) filter
      devices in Japanese patients. METHODS AND RESULTS: In 42 Japanese patients with
      deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) who underwent
      percutaneous insertion of IVC filters, follow-up examinations at fixed intervals
      of 2 years were performed, and the data was evaluated including complications.
      There were no fatal complications during IVC filter implantation. About 5% of
      patients with an inserted IVC filter developed symptomatic PTE, another 5%
      developed asymptomatic PTE. The trapped thrombus was demonstrated in about 22% of
      the inserted IVC filters. Lower rates of PTE development, occlusion of IVC, and
      captured thrombus were found in the cases where concurrent use of anticoagulation
      therapy with filters was used. Trapped thrombi were found in half of IVC filters
      inserted prophylactically for proximal femoral venous thrombosis. CONCLUSION:
      These experiences with IVC filters suggest that they are safe and effective for
      the prevention of PTE in the Japanese population.

PMID- 10969902
TI  - Usefulness of serum hepatocyte growth factor for the diagnosis of amyloidosis.
AB  - OBJECTIVE: The diagnosis of amyloidosis still relies on biopsy, but there has
      been a growing demand for the development of a specific noninvasive diagnostic
      technique. Hepatocyte growth factor (HGF) acts on a variety of epithelial cells
      in multiple ways and is predominantly produced by mesenchymal cells and
      macrophages. In the present study, we measured the serum HGF level in patients
      with amyloidosis and investigated its usefulness for the diagnosis of this
      disease. METHODS: The subjects were 18 patients diagnosed as having amyloidosis
      by biopsy. We also measured serum HGF in 47 patients with chronic
      glomerulonephritis, 32 patients on hemodialysis, and 24 healthy volunteers. The
      serum HGF level was measured using an HGF ELISA kit. RESULTS: The serum HGF level
      of patients with amyloidosis was significantly increased compared with that of
      healthy volunteers, patients with chronic glomerulonephritis, and hemodialysis
      patients (2.26+/-2.73 ng/ml versus 0.20+/-0.04 ng/ml, 0.23+/-0.08 ng/ml, and
      0.18+/-0.07 ng/ml respectively, p<0.0001). There was no significant difference
      between amyloid light-chain and amyloid A amyloidosis, but the serum HGF level of
      amyloidosis patients who died within 1 year of measurement was significantly
      higher than that of patients who lived for more than 1 year (2.83+/-2.85 ng/ml
      versus 0.49+/-0.26 ng/ml, p<0.01). CONCLUSIONS: The serum HGF level was
      significantly elevated in both amyloid light-chain and amyloid A amyloidosis and
      was a very useful indicator of suspected amyloidosis as well as a potential
      prognostic indicator. The serum HGF level may become a useful indicator for
      diagnosing amyloidosis.

PMID- 10969903
TI  - Awareness of the harmful effects of smoking and views on smoking cessation
      intervention among Japanese medical students.
AB  - OBJECTIVE: To clarify attitudes toward smoking, and views on smoking intervention
      among medical students, as well as to teach them the harmful effects of smoking.
      SUBJECTS AND METHODS: We carried out an anonymous questionnaire among 2nd and 5th
      year Japanese medical students and 1,137 of them responded. RESULTS: Smoking
      prevalence was 25.1% in men and 8.8% in women in the 2nd year and 43.1% and 9.3%,
      respectively, in the 5th year. Most respondents thought smoking is harmful to
      health, but smokers were more likely to think it is not so harmful. In both
      groups, 97% of the respondents knew lung cancer was related to smoking. Apart
      from this, knowledge of smoking-related diseases (pulmonary emphysema, coronary
      heart disease, peptic ulcer, and neonatal death) increased by the 5th year but
      the rates of recognition were generally less than 50%. Many of them learned about
      the deleterious effects mainly at places other than medical class (80.2% in the
      2nd, 44.9% in the 5th year). About 90% intended to perform smoking intervention
      in the future, but only one-third were actively interested. More than 70% of the
      respondents thought that doctors should carry out smoking cessation advice
      depending on the disease, while the rate of those who thought so irrespective of
      the disease did not reach 20%. Smokers thought less actively about smoking
      intervention than current nonsmokers. CONCLUSION: The awareness of the harmful
      effects of smoking and intention to perform smoking intervention in the future as
      doctors seemed unsatisfactory among Japanese medical students.

PMID- 10969904
TI  - Deep white matter lesions on MRI, and not silent brain infarcts are related to
      headache and dizziness of non-specific cause in non-stroke Japanese subjects.
AB  - OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an
      important risk factor for symptomatic stroke and vascular dementia. Although non
      specific complaints such as mild to moderate headache and/or dizziness may also
      be caused by silent stroke, which remains a topic of controversy. METHODS: To
      investigate the relationship between silent brain infarcts and non-specific
      complaints, we assessed findings on magnetic resonance images using a common
      protocol in the following three groups of subjects; Group 1:78 subjects with non
      specific complaints, Group 2:47 subjects with vascular risk factors, and Group
      3:75 normal subjects without any subjective complaints or vascular risk factors.
      In addition to silent stroke, deep white matter lesions on MRI were also
      evaluated. All subjects were recruited from 12 institutes of the study group
      located at various parts of Japan. RESULTS: Silent brain infarcts were
      demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3,
      respectively. In Group 1, the average number of infarcts per individual who had
      silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group
      2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and
      11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints
      are more closely related to deep white matter lesions than to silent infarct
      lesions. Such white matter lesions were found more frequently in subjects with
      depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155).
      CONCLUSION: The present results suggest that deep white matter lesions, rather
      than silent brain infarcts, appear to be important in producing headache and/or
      dizziness of non-specific cause and also to be related to the depressive state.

PMID- 10969905
TI  - Arg133Cys mutation of Notch3 in two unrelated Japanese families with CADASIL.
AB  - OBJECTIVE: More than 80 unrelated, but all Caucasian, patients with cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), originating from various communities around the world, have been
      molecularly identified. To clarify the occurrence of CADASIL in Orientals, we
      investigated Japanese families presenting as CADASIL. METHODS: We performed the
      PCR-SSCP and sequence analyses using genomic DNA, isolated from venous blood of
      participants under informed consent. PATIENTS: We identified two unrelated
      Japanese families with CADASIL, including 5 affected members through 2
      generations. RESULTS: Each of the affected individuals developed recurrent
      strokes without risk factors resulting in progressive dementia, pseudobulbar
      palsy, and gait disturbances which started after the fifth decade of life.
      Although affected individuals had no vascular risk factors, they showed various
      degrees of narrowing of retinal arteries. Their MRI/CTs showed characteristics of
      the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem,
      and deep white matter in addition to the findings of leukoaraiosis. On SPECT
      imaging, there was severe hypoperfusion in the cortex as well as in the white
      matter. Ultrastructural studies revealed an abnormal deposition of granular
      osmiophilic materials (GOM) within the basal lamina of pericytes in muscular
      capillaries. On PCR-SSCP and sequence analyses, a heterozygous Arg133Cys mutation
      was present, in the affected individuals, in the exon 4 of Notch3 gene which is
      the hot spot region for CADASIL mutations in Caucasian families. None of the non
      affected members nor the 50 Japanese normal controls revealed this mutation.
      CONCLUSION: Thus, our results confirm that CADASIL is a geographically widespread
      disorder caused by a Notch3 mutation.

PMID- 10969906
TI  - Pulmonary lymphangiomyomatosis (LAM) developing chylothorax.
AB  - We describe a case of pulmonary lymphangiomyomatosis (LAM) with chylothorax that
      developed in a 46-year-old Japanese woman. This patient exhibited clinical
      symptoms of dyspnea and chest X-ray showed right pleural effusion.
      Thoracocentesis demonstrated chylous effusion. Chest computed tomography (CT)
      scan revealed multiple cystic lesions. Subsequent thoracoscopy revealed the
      chylorrhea from swelled vessels on the diaphragm. The clinical diagnosis, based
      on histological examinations with biopsy specimens obtained by thoracoscopy, was
      pulmonary LAM. Although the hormone therapy was not effective, chylous effusion
      was improved by the pleurodesis. Pulmonary LAM developing chylothorax is rare in
      Japan.

PMID- 10969907
TI  - Thymoma with pemphigus foliaceus.
AB  - A 75-year-old Japanese woman was referred to us because of an anterior
      mediastinal mass. Crusts and shallow erosions developed 10 months earlier on her
      upper chest, back, and scalp. Pemphigus foliaceus was diagnosed based on
      histological examination of skin biopsy specimens and positivity for serum anti
      desmoglein 1 antibody by enzyme-linked immunosorbent assay. Neurological
      examination and electromyography ruled out myasthenia gravis. Total thymectomy
      was performed, and the postoperative pathology studies showed mixed
      lymphoepithelial thymoma. One year after the resection, the eruption and alopecia
      improved and the serum anti-desmoglein 1 antibody titer decreased, suggesting a
      beneficial effect of thymectomy on thymoma-related pemphigus.

PMID- 10969908
TI  - Primary antiphospholipid syndrome presenting with cerebral ischemia,
      thrombocytopenia, anemia and proteinuria successfully treated with warfarin
      potassium.
AB  - A 30-year-old woman with primary antiphospholipid syndrome (PAPS) presented with
      cerebral ischemia, thrombocytopenia, anemia and proteinuria. Administration of
      warfarin potassium, without concomitant corticosteroid administration,
      significantly improved all of these symptoms along with a decrease in the titers
      of antiCL-beta2-GP-I antibodies and a shortening of prolonged APTT. Therefore,
      the antiphospholipid antibodies in this patient could have been evoked by vitamin
      K-dependent coagulation factors or plasma proteins which are assumed to undergo
      conformational changes exposing cryptic epitopes. This case report provides clues
      to the mechanisms underlying the production of antiphospholipid antibodies in
      patients with PAPS.

PMID- 10969909
TI  - Palmar fasciitis and polyarthritis associated with gastric carcinoma: complete
      resolution after total gastrectomy.
AB  - Palmar fasciitis and polyarthritis (PFA) is a rare paraneoplastic rheumatic
      syndrome characterized by flexion contractures of both hands and thickening of
      palmar fascia. Several reports have suggested that this syndrome is a tumor
      associated autoimmune disorder. We report a 44-year-old Japanese man who
      presented with flexion contractures of both hands associated with thickening of
      palmar fascia and polyarthritis. These clinical pictures were suggestive of PFA
      associated with occult neoplasm. Upper gastrointestinal endoscopic examination
      revealed advanced gastric cancer. Resection of the cancer resulted in a gradual
      resolution of palmar fasciitis and polyarthritis. This clinical course suggests
      an underlying tumor-related immunologic process in this syndrome.

PMID- 10969910
TI  - Etiology of central precocious puberty in males: the results of the Italian Study
      Group for Physiopathology of Puberty.
AB  - We reviewed the hospital records of 45 boys, followed in 13 pediatric departments
      throughout Italy, who had undergone computed tomography and/or magnetic resonance
      imaging for central precocious puberty (CPP). Twenty-seven patients (60%) had
      idiopathic CPP and 18 (40%) neurogenic CPP. A hamartoma of the tuber cinereum was
      found in six patients (33%). All patients with hypothalamic hamartoma had earlier
      onset of symptoms than patients with idiopathic CPP. Five patients (27%) were
      affected by type 1 neurofibromatosis, two had ependymoma and five patients had an
      intracranial anomaly. Basal LH and basal and peak LH/FSH ratio were greater, but
      not significantly, in boys with neurogenic CPP than in boys with idiopathic CPP.
      The highest LH peak levels were observed in patients with hamartoma; however, no
      correlation was observed between LH peak and the size of the hamartomas. In
      addition, bone age at diagnosis was more advanced in patients with hamartoma than
      in patients with other conditions. In conclusion, gonadotrophin-dependent
      precocious puberty may be of idiopathic origin or may occur in association with
      any CNS disorder. Further studies are needed in order to evaluate the effects of
      nutritional, environmental and psychosocial factors on the timing of sexual
      maturation, to explain the high incidence of idiopathic CPP in our male patients.

PMID- 10969911
TI  - Etiology and age incidence of precocious puberty in girls: a multicentric study.
AB  - We review the etiology and age incidence of precocious puberty in 438 girls
      examined between 1988-1998; 428 (97.7%) had central precocious puberty (CPP), the
      remaining 10 (2.3%) gonadotropin-independent precocious puberty (GIPP) of ovarian
      origin. The majority of CPP girls (59.6%) were aged between 7-7.9 yr, 22.4% were
      6 year olds, and only 18% were under 6 years old. Cranial CT and/or MRI performed
      in 304/428 girls, showed neurogenic abnormalities in 56/304 (18.4%) CPP girls; 30
      (9.9%) were due to previously diagnosed intracranial abnormalities and the
      remaining 26 (8.5%) were detected at the diagnosis of CPP. The frequency of
      neurogenic CPP tended to be higher in girls under 4 years of age while the
      frequency of idiopathic CPP tended to be higher in girls aged between 7-7.9
      years, but no statistically significant differences were found. Interestingly,
      some CNS anomalies either of tumoral or congenital origin were detected at
      presentation in 7% of the girls aged over 7 years. Other related or coincidental
      clinical anomalies, mainly due to genetic diseases, were observed in 22/304
      (7.2%) patients. History of precocious maternal menarche was found in 12/304 (4%)
      girls. In conclusion, idiopathic CPP was observed in 74% of the girls in this
      study. Neurogenic anomalies or other coincidental or related clinical findings
      were observed in the remaining 26%. The increased frequency of idiopathic CPP in
      girls aged over 7 years may suggest an early, but otherwise normal onset of
      puberty in many of these girls as a consequence of the trend towards earlier
      maturation. Nonetheless, the finding of CNS anomalies also in the older patients,
      raises the question of whether these patients should undergo a complete
      diagnostic work-up.

PMID- 10969912
TI  - Central precocious puberty: clinical and imaging aspects.
AB  - We review briefly the definition of central precocious puberty (CPP), and discuss
      early puberty and very early puberty. The association of hypothalamic hamartoma
      and empty sella with CPP is described. The contribution of new imaging techniques
      - CT, MRI and ultrasound in the differential diagnosis of CPP is discussed.

PMID- 10969913
TI  - Diagnosis of central precocious puberty: endocrine assessment.
AB  - The new methods which are currently available have provided substantial help in
      performing the differential diagnosis of CPP, especially in detecting very early
      modifications of gonadotropin secretion. Nocturnal sampling is not a practical
      tool and generates discomfort for patients, and daytime samples do not yet have
      sufficient sensitivity; thus, determination of LH levels after GnRH stimulation
      is the most important test. We emphasize that the use of the GnRH agonist test
      improves the discrimination of the endocrine investigation, making it easier to
      differentiate CPP from other conditions, such as thelarche. Determination of sex
      steroids is necessary, but its use in isolation is not recommended.

PMID- 10969914
TI  - Body fat mass, leptin and puberty.
AB  - Leptin, the ob gene product, provides a molecular basis for the lipostatic theory
      of the regulation of energy balance. Leptin circulates as a monomeric 16 kDa
      protein in rodent and human plasma and is also bound to leptin binding proteins
      that may form large high molecular weight complexes. Initial models of leptin
      action included leptin-deficient ob/ob mice and leptin-insensitive db/db mice.
      Peripheral or central administration of leptin reduced body weight, adiposity,
      and food intake in ob/ob mice but not in db/db mice. In ob/ob mice leptin
      treatment restored fertility. Leptin interacts with many messenger molecules in
      the brain. For example, leptin suppresses neuropeptide Y (NPY) expression in the
      arcuate nucleus. Increased NPY activity has an inhibitory effect on the
      gonadotropin axis and represents a direct mechanism for inhibiting sexual
      maturation and reproductive function in conditions of food restriction and/or
      energy expenditure. By modulating the hypothalamo-pituitary-gonadal axis both
      directly and indirectly, leptin may thus serve as the signal from fat to the
      brain about the adequacy of fat stores for pubertal development and reproduction.
      Normal leptin secretion is necessary for normal reproductive function to proceed
      and leptin may be a signal allowing for the point of initiation of and
      progression toward puberty.

PMID- 10969915
TI  - Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in
      pediatrics.
AB  - Since 1981, GnRH agonist administration has been the treatment of choice for
      central precocious puberty. Continuous administration of the agonist, instead of
      permanently stimulating gonadotropin secretion, deeply suppresses LH and FSH
      levels and induces a marked inhibition of gonadal activity and regression of
      clinical symptoms. This inhibitory effect is due both to specific kinetic
      parameters relative to natural GnRH, and to marked alterations of the
      biosynthetic pathways of gonadotropin subunits. The half disappearance time of
      infused agonists is 3-10 fold that of natural GnRH. This means that the residence
      time of GnRH agonists is significantly longer than that of GnRH. The resistance
      of agonist to enzymatic degradation, mainly due to the substitution of a
      hydrophobic D-amino acid for glycine 6, is one of the factors involved in the
      increased availability of GnRH superagonists. The paradoxical effects of GnRH
      superagonists are still incompletely understood. In children long-term treated
      with depot formulations of triptorelin or leuprorelin, alpha-subunit secretion is
      markedly increased, and remains sensitive to exogenous GnRH, which demonstrates
      that the gonadotrophs are not totally desensitized. Despite the sustained
      stimulation of a-subunit secretion, no deleterious side effects, either during
      therapy or during post-therapy follow-up, have been reported in children treated
      with GnRH agonists. It should be noted that alpha-subunit responsiveness to
      exogenous GnRH decreases progressively after several years of treatment, although
      it is never completely abolished. On the other hand, LH beta-subunit secretion is
      suppressed as evidenced by radioimmunoassay of LH beta-subunit in serum
      chromatographic fractions from children treated with triptorelin. This
      differential pattern of secretion parallels that of mRNA levels in rat pituitary
      after in vivo exposure to triptorelin. Both pharmacodynamic and pharmacokinetic
      data can help diagnose the situations of resistance or escape. The lack of
      clinical effect of GnRH in the treatment of precocious puberty can be due to true
      resistance, or to an inappropriate injection schedule, or to abnormal metabolism.
      Measurement of serum alpha-subunit level, and, if needed, of serum agonist level,
      generally provides the answer.

PMID- 10969916
TI  - Hormonal changes during GnRH analogue therapy in children with central precocious
      puberty.
AB  - Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of
      central precocious puberty (CPP) for more than 15 years. They are generally
      considered safe although data on potential long-term side effects are scarce.
      However, GnRHa therapy has profound effects on both the hypothalamopituitary
      gonadal axis as well as on growth hormone (GH) secretion. Gonadal activity is
      increased in children with CPP; during GnRHa therapy secretion of gonadal
      hormones is suppressed as reflected by measurements of LH, FSH, and
      estradiol/testosterone. More recently, studies of levels of inhibin A and B as
      well as markers of androgen action such as SHBG and prostate specific antigen
      have demonstrated marked suppression of gonadal function possibly to infra
      physiological levels. The possible long-term consequences of these observations
      have yet to be determined. Detailed analyses of the GH-IGF-I axis have revealed a
      decrease in levels of free, biologically active IGF-I during GnRHa treatment.
      These findings are in accord with the observed decrease in height velocity in
      children with CPP under treatment with GnRHa, and may also play a role in the
      relatively small gain in final height in most patients.

PMID- 10969917
TI  - Treatment of central precocious puberty: lessons from a 15 years prospective
      trial. German Decapeptyl Study Group.
AB  - There is still controversy about the auxological outcome of GnRH agonist
      treatment in patients with CPP and about the favorable age and auxological
      characteristics at start of treatment for achieving a normal final height (FH) or
      for preserving height potential. We analyzed the FH data of 52 young women from a
      prospective multicentric trial which was started in 1985. The aim of this
      analysis was to determine factors that may predict a favorable FH or a good
      height gain. Chronological age (CA) was 5.2 +/- 2.1 yr (+/- SD) at start of
      puberty, 6.2 +/- 2.0 yr at start of triptorelin depot treatment, 11.1 +/- 1.1 yr
      at end of treatment, and 16.7 +/- 2.6 yr at FH evaluation. After 4.8 +/- 2.2 yr
      (1.1-9.9 yr) of treatment duration, FH was 160.6 +/- 8.0 cm (vs 154.9 +/- 9.6 cm
      of initial height prediction [PAH], p<0.05). A FH within TH range or in excess of
      mean TH was achieved by 78% or 41% of patients. FH was above the 3rd percentile
      of the normal German population in 29% of patients (63% had an initial PAH < 156
      cm). The group of patients with start of puberty at age < or = 6 yr (Group 1)
      showed a significantly higher height gain (FH - initial PAH) and lower height
      deficit compared to TH than older patients (Group 2). Furthermore, the percentage
      of patients from Group 1 reaching TH range or mean TH showed a significant
      increase with GnRH agonist treatment whereas this was not the case in Group 2.
      Stepwise regression analysis showed that height SDS at end of treatment, age at
      menarche, bone age (BA) at start of treatment, and BA advancement at end of
      treatment were determinants of FH (r2=0.923). Initial BA advancement and
      treatment duration were the factors that explained 68% of the variability of
      height gain. Although BA advancement at initiation of treatment was negatively
      associated with FH it was a positive predictor of height gain. In addition,
      height gain correlated significantly with CA and BA at start of treatment (r= 
      0.430, p=0.004 and r=0.359, p=0.018). Growth after interruption of treatment had
      no significant predictive effect on FH. It is concluded that a higher percentage
      of patients below 6 yr of age at start of puberty do profit from GnRH agonist
      treatment with respect to achieving a normal FH. BA, BA advancement, and height
      SDS at treatment start are important factors for determining outcome.

PMID- 10969918
TI  - When to stop GnRH analog therapy: the experience of the Italian Study Group for
      Physiopathology of Puberty.
AB  - Data reported in this study have been recently published elsewhere. The authors
      retrospectively analyzed the auxological response to GnRH agonist treatment and
      the final height (FH) outcome in 71 girls with idiopathic and truly precocious
      (onset before 8 years) central puberty (CTPP), who had been treated with the same
      therapy protocol (Decapeptyl Depot at the dose of 60 microg/kg i.m. every 28
      days) for at least 2 years (since 7.0 +/- 1.3 yr) and followed until puberty was
      completed and FH was reached. During the entire treatment period we observed: A)
      a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3
      SDS, p<0.01); B) a striking deceleration of BA, revealed by the subnormal
      deltaBA:deltaCA ratio (0.2 +/- 0.1); C) an increase of predicted adult height
      (from 155.6+/-7.0 to 160.7+/-6.7 cm, p<0.0005). Treatment interruption was
      followed by notable catchdown growth, with FH (158.4 +/- 5.8 cm) lower (p <
      0.025) with respect to that predicted at the end of therapy. However FH fell
      within the population norm and the target range in 87.3% and 90% of patients,
      respectively. The tallest FH was recorded in the patients who discontinued
      treatment at a BA of 12.0-12.5 years. We conclude that: 1) Most girls with
      idiopathic CTPP treated by GnRH agonists may achieve an adult height within the
      population norm and/or their target range; 2) The height gain from therapy onset
      until FH attainment, however, is generally rather limited (on average 2.9 cm) and
      only few patients are able to reach their target percentile; 3) The most
      favorable height prognosis with respect to target height (TH) is generally
      observed in the patients with the tallest H2 and the lowest BA2:CA2 ratio, due to
      the notable deterioration of height prognosis which frequently follows therapy
      interruption; 4) In order to strengthen the weak therapeutic effect of GnRH
      agonists in CTPP, this treatment should be discontinued at a BA of 12-12.5 years.

PMID- 10969919
TI  - Final height after gonadotrophin releasing hormone agonist treatment for central
      precocious puberty: the Dutch experience.
AB  - Final height (FH) data of 96 children (87 girls) treated with GnRH agonist for
      central precocious puberty were studied. In girls mean FH exceeded initial height
      prediction by 7.4 (5.7) cm (p < 0.001); FH was significantly lower than target
      height, but still in the genetic target range. When treatment started < 6 years
      of age, height gain was significantly higher than when started > 8 years of age.
      Bone age (BA) and chronological age (CA) at start of treatment, as well as BA
      advance at cessation of treatment, were the most important variables influencing
      height gain in multiple regression analysis. BA advance at start of treatment was
      most important in simple correlation. In girls, GnRHa treatment seems to restore
      FH into the target range. A younger age and advanced bone age at start of
      treatment are associated with more height gain from GnRHa treatment.

PMID- 10969920
TI  - End results in central precocious puberty with GnRH analog treatment: the data of
      the Italian Study Group for Physiopathology of Puberty.
AB  - We report some end results with GnRH agonist (GnRHa) treatment in central
      precocious puberty (CPP), in terms of final height (FH), ovarian function, peak
      bone mass, body composition and psychological problems. The two studies reported
      (Study I and II) are part of the activity of the Italian Study Group for
      Physiopathology of Puberty. Study L Growth data were analyzed of three groups of
      patients: treated with i.n. spray buserelin, i.m. triptorelin and untreated. Both
      GnRHa administration modes were effective in arresting pubertal development and
      all girls had complete recovery of the reproductive axis after therapy. Treated
      patients showed an improvement in final height in comparison with untreated
      patients and compared to predicted height at the start of treatment with both
      agonist treatments. However, patients treated with the long-acting slow release
      preparation had a better improvement in adult height and reached or exceeded the
      genetic height potential. Study II. In a retrospective evaluation of the outcome
      in 71 girls with idiopathic CPP treated with triptorelin, we found that FH fell
      within the population norm and the target range in 87.3% and 90% of the patients
      respectively. The tallest FH was recorded in the patients who started therapy at
      less than 6 years of age and in those who discontinued treatment at a bone age of
      12.0-12.5 yr. Finally, we and other groups have recently found normal values of
      bone mineral density in girls at the end of GnRHa treatment in the great majority
      of patients.

PMID- 10969921
TI  - Factors influencing final/near-final height in 12 boys with central precocious
      puberty treated with gonadotrophin-releasing hormone agonists. Italian Study
      Group of Physiopathology of Puberty.
AB  - Gonadotrophin-releasing hormone agonists (GnRHa) have been demonstrated as the
      therapy of choice for central precocious puberty (CPP). Few studies have provided
      male patients' adult height data. In our multicenter study we evaluated long-term
      effects of different GnRHa preparations and final/near-final height (FH) in 12
      boys with CPP and analyzed the factors influencing FH. Patients' mean
      chronological age at the time of diagnosis was 7.6 +/- 0.9 yr. Three patients
      were treated only with triptorelin at a mean dose of 90 microg/kg i.m. every 28
      days. Nine patients initially received buserelin (at a mean initial dose of 53.4
      microg/kg/day i.n. divided into 3-6 equal doses) or buserelin (at a mean dose of
      36.7 microg/kg/day s.c.) and were subsequently switched to triptorelin. The GnRHa
      therapy was continued for 4.1 +/- 0.6 yr (range 2.9-5.4). The mean predicted
      adult height increased from 169.9 +/- 4.2 cm at diagnosis to 180.7 +/- 6.0 cm at
      the end of treatment. Mean FH was 176.1 +/- 6.1 cm (170.1-190.7), corresponding
      to mean SDS(CA) 0.4 +/- 0.8 (-0.6/2.5), mean SDSBA 0.2 +/- 0.9 (-0.6/2.4) and
      mean corrected SDS for target height of 0.4 +/- 0.6 (-0.8/1.2). Multiple
      regression analysis revealed that FH was mainly influenced by target height and
      height at discontinuation of GnRHa therapy. The present data indicate that GnRHa
      therapy significantly improves growth prognosis in boys with CPP and fully
      restores genetic height potential.

PMID- 10969922
TI  - Near final height after GnRH agonist treatment in central precocious puberty.
AB  - The impact of treatment of central precocious puberty (CPP) with gonadotropin
      releasing hormone agonists (GnRHa) on final height remains controversial. We
      analyzed the long term results of 23 girls with CPP treated with triptorelin or
      leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14
      years and expressed as SDS, was compared either with predicted height before
      treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls
      treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after
      8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not
      different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS).
      Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later
      treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height
      (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our
      patients, treated either earlier or later, reached a near final height comparable
      to predicted height and familial target; however, these results might still
      improve further because the girls have not yet reached their final adult height.

PMID- 10969923
TI  - Precocious puberty and body composition: effects of GnRH analog treatment.
AB  - INTRODUCTION: Body composition changes with age and sex differences become
      significant only after puberty. Boys and girls before the age of 8 yr do not
      differ in fat, lean or bone mineral mass. Hormonal influences during pubertal
      development determine the physiological adult male and female body composition
      phenotype. AIM: The aim of our study was to evaluate body composition changes due
      to central precocious puberty (PP) and the specific effects of therapy on these
      modifications. SUBJECTS AND METHODS: Sixteen patients (14 girls, 2 boys) were
      included in the study. They were diagnosed as affected by idiopathic PP according
      to standard hormonal and clinical criteria; anatomic alterations of hypothalamus
      hypophysis region were excluded by MRI. Mean age at diagnosis was 5.9 +/- 1.9 yr.
      All patients received GnRH analog (Leuprolide or Triptorelin) treatment
      subcutaneously every 4 weeks for at least 1 yr. Mean period of treatment was 3.4
      +/- 1.9 yr. Standard anthropometry and body composition analysis were performed
      at baseline and every 6-12 months. A group of healthy subjects with normal timing
      of puberty was matched (for age or for pubertal stage) served as the control
      group (CA or CP, respectively). RESULTS: Patients with PP showed at baseline a
      significant increase of BMI and relative body weight; lean and fat compartments
      were also increased but not significantly. During treatment, the PP group showed
      increased fat mass compared to CA (p<0.05), while no difference was found between
      PP and CP. Lean mass was similar to CA but lower than in CP (p<0.05). During
      treatment a significant increase in lean mass (both as total as well as limb
      mass) was observed. After stopping treatment there was no difference between PP
      and CP, except for lower lean mass (p<0.04). CONCLUSION: When puberty occurs
      precociously, lean and fat mass are not significantly different from age-matched
      control subjects. Data collected during treatment confirm a shortening of
      prepubertal lean mass development and the block of further lean mass development
      due to puberty itself, while fat mass accumulation continues. The net result of
      these modifications determines a typical body composition pattern in PP patients,
      after the end of therapy: lean mass is reduced by a shortening of the prepubertal
      growing period and by the "menopausal effect" of treatment itself. Fat mass is
      increased as a consequence of therapy and could lead to future obesity.

PMID- 10969924
TI  - Side effects of GnRH analogue treatment in childhood.
AB  - There are a few reports of side-effects of LHRHa treatment in childhood, the
      mechanisms of which remain little understood. Such effects can be local
      reactions: erythema, induration, wheal and sterile abscess formation, which can
      be possible causes of therapy failure. There are negative effects on growth
      velocity and final height requiring rhGH therapy or a suppressive treatment when
      bone age >13 years. Excessive weight gain can occur by various mechanisms:
      menopausal-like phenomena, or LHRHa influence on hypothalamic and/or leptin
      mediated control of body weight. Other possible adverse effects involve increased
      ovarian volume with possible POS development; however, there is no evidence
      correlating LHRHa, hyperandrogenism and POS. The latter appears related to CPP
      onset with pre-existing hyperandrogenism, although lengthier follow-up is
      necessary to confirm this. Bone density decreases during therapy, but final peak
      bone mass is in the normal range. Frequent transitory side-effects include
      headaches, hot flushes, depression and irregular menses.

PMID- 10969925
TI  - Experience with cyproterone acetate in the treatment of precocious puberty.
AB  - The authors review their experience (1967-present) in the use of cyproterone
      acetate (CPA) in precocious puberty. CPA was found effective in persistently
      suppressing pituitary gonadotropic secretion when administered orally at a dose
      of 50 mg b.i.d. (70-100 mg/d). After the introduction of gonadotropic analogues
      (GnRHa) for treatment of central precocious puberty, short term use of CPA was
      found useful to counteract the initial stimulatory effect of the GnRHa as well as
      an adjunct drug in case of very active adrenarche causing advanced bone age
      during GnRHa treatment. The final heights of girls treated with CPA and girls
      treated with D-Trp6-LHRH were found comparable: 157.8+/-5.1 cm vs 159.6+/-6.3 cm,
      respectively. The main adverse effects were occasional fatigue due to partial
      adrenal insufficiency with CPA and gynecomastia in a few boys. Liver function
      tests were normal in all patients with the exception of one boy with severe
      hypothalamic disease, including precocious puberty, who developed liver cirrhosis
      3 years after stopping CPA following 5 years treatment. Other indications for CPA
      treatment during childhood and adolescence, such as fast puberty, congenital
      adrenal hyperplasia and acne, are also mentioned.

PMID- 10969926
TI  - Combined therapy with GnRH analog plus growth hormone in central precocious
      puberty.
AB  - GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocity (GV)
      and bone maturation, thus improving adult height in central precocious puberty
      (CPP). In some patients, however, GV decreases to such an extent that it
      compromises the improvement in predicted adult height (PAH) and therefore the
      addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with
      GnRHa [depot-triptorelin] at a dose of 100 microg/kg every 21 days i.m. for at
      least 2-3 yr) whose GV fell below the 25th percentile for chronological age (CA),
      ten received, in addition to the GnRHa, GH at a dose of 0.3 mg/kg/wk, s.c. 6 days
      weekly, for 2-4 yr. Ten patients matched for BA, CA, and duration of GnRHa
      treatment who showed the same growth pattern but refused GH treatment, served to
      evaluate the efficacy of the addition of GH. No patient showed classical GH
      deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM):
      13.2 +/- 0.2 yr in GnRHa + GH vs 13.0 +/- 0.1 yr in the control group. At the
      conclusion of the study all the patients had achieved adult height. Adult height
      was considered to be attained when the growth during the preceding year was less
      than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH + GnRHa
      showed an adult height significantly higher (p<0.001) than pretreatment PAH
      (160.6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased
      from -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.001).
      Target height was significantly exceeded. The GnRH alone treated group reached an
      adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs
      155.5 +/- 1.9 cm). Height SDS for BA did not change (from -1.0 +/- 0.3 at start
      of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not
      significantly exceeded. The gain in centimeters obtained calculated between
      pretreatment PAH and final height was 7.9 +/- 1.1 cm in patients treated with GH
      combined with GnRH analogue while in patients treated with GnRH analogue alone
      the gain was just 1.6 cm +/- 1.2 (p=0.001). Furthermore, no side effects, bone
      age progression, or ovarian cysts, were observed in GnRHa + GH treated patients.
      In conclusion, a gain of 7.9 cm in adult height represents a significant
      improvement which justifies the addition of GH for 2-3 yr to conventional
      treatment with GnRH analogues in patients with central precocious puberty, and
      with a decrease in growth velocity so marked as to impair predicted adult height
      to below the third percentile.

PMID- 10969927
TI  - Is there a place for combined therapy with GnRH agonist plus growth hormone in
      improving final height in short statured children?
AB  - The availability of recombinant human growth hormone (GH) and the optimization of
      substitutive therapy have improved final growth in children with GH deficiency,
      but despite this some of them fail to grow to their genetic potential. In
      particular, this may occur in patients who started the substitutive therapy too
      late and/or in whom bone age progressed too fast during GH administration. In
      these patients, with unfavorable auxological characteristics, the administration
      of a GnRH agonist in combination with GH may slow down bone maturation and
      prolong prepubertal growth, mimicking, to some extent, the growth pattern of
      patients with GH + Gn deficiency who grow better than children with isolated GHD.
      A different condition in which such a combined therapy might be used is the short
      normal child. As they are short but normally-growing children, the onset of
      puberty is in general appropriate for their chronological age but precocious for
      their height age. Thus, slowing down pubertal maturation may increase the time
      available for growth. GH would sustain growth during both GnRHa administration
      and after its withdrawal, when puberty starts again. Our preliminary results
      suggest that the administration of GH + GnRHa in combination may have a positive
      effect on final height in selected children with isolated GHD and in short normal
      children.

PMID- 10969929
TI  - Precocious puberty in immigrant children: indications for treatment.
AB  - Immigration from developing countries to Europe has greatly increased during the
      last few years. Very little information is available on children who immigrated
      with their biological family, thus this paper deals only with children
      immigrating by adoption. In recent years some studies have shown an increased
      incidence of precocious puberty among adopted children, but information on this
      issue is scanty. Several hypotheses have been put forward to explain precocious
      puberty in adopted children, including nutritional, ethnic and/or emotional
      factors. Untreated precocious puberty is associated with short stature and has
      social and psychological consequences in addition to those related to adoption.
      Therefore, indications for therapy need to be carefully planned. In adopted
      children age estimation is a possible source of error in timing of puberty as
      date of birth is often missing or inaccurate. Thus each child must be carefully
      evaluated.

PMID- 10969928
TI  - Premature thelarche: clinical follow-up and indication for treatment.
AB  - Not only is the diagnosis of isolated premature thelarche difficult to
      distinguish from other variants of premature sexual maturation, but within the
      subgroups of isolated premature thelarche, there are probably at least two
      subgroups: "classical" and "atypical". We do not appreciate how potential
      treatment could affect each group, although it seems likely that those in the
      "classical" group would not have an indication for treatment. The longer-term
      follow-up of large numbers of patients is essential if we are to understand the
      long-term sequelae of this condition.

PMID- 10969930
TI  - Adolescent girls with idiopathic central precocious puberty: typical character
      traits.
AB  - It has been reported that girls at onset of idiopathic central precocious puberty
      (ICPP) and during treatment have symbiotic character traits. The aim of this
      study was to investigate the development of character in a group of adolescents.
      Ten adolescent girls aged 14 years treated for ICPP were evaluated. All the
      adolescents in the study had a negative body image compared with age-matched
      controls and expressed a strong inhibition of their femininity. Their poor body
      image is reflected by their limited self-esteem. These adolescents have not been
      able to operate a reorganization of their affective life and therefore go through
      the necessarily slow and painful separation from their family. Symbiotic traits
      are "hard-wired" into their lives. These results suggest that at ICPP onset, in
      addition to setting up an educational program for the parents, it is equally
      important to supply psychological support for the patients in order to gain a
      better interaction between biological, psychological and cultural influences.

PMID- 10969931
TI  - Neurofibromatosis type 1 and precocious puberty.
AB  - Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty
      (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP,
      the association with optic pathway tumors (OPT), and other clinical, auxological
      and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%),
      and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients
      with PP involved the chiasm in four patients, and the optic nerves alone in three
      patients. The age at the onset of puberty (or better at diagnosis) ranged from
      5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist
      therapy was used in only three children because in the others the predicted
      height at diagnosis was good, treatment was refused or the patients were referred
      to us too late. The three treated patients attained a final height within the
      familial range. In the untreated patients the progression of puberty was not too
      rapid and final height was slightly below the genetic target in four patients;
      however, three patients had a final height markedly below the familial range. In
      conclusion, the prevalence of PP is increased in children with NF1, and
      frequently but not exclusively is associated with OPT. Moreover, sexual precocity
      does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be
      useful in the children with younger age at the onset of puberty or with a
      progressive decline in predicted final height.

PMID- 10969932
TI  - Gonadotropin-dependent sexual precocity in a boy affected by
      pseudohypoparathyroidism.
AB  - Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and
      hyperphosphatemia due to PTH resistance. PHP type Ia is due to diminished
      G(s)alpha activity in several tissues, causing resistance to hormones whose
      action is mediated by cAMP. Only two cases of males with PTH type Ia who
      paradoxically showed sexual precocity have been described in the literature. We
      describe an 11.5 year-old boy affected by PHP without AHO but with associated
      true precocious puberty, who came to the I.C.U. for tetanic seizures and
      drowsiness due to severe hypocalcemia. Hyperphosphatemia, increased PTH levels
      and normal 25-OH-vitamin D values were present. Skeletal X-ray showed mild
      osteopenia. Brain MRI revealed symmetric calcifications in basal ganglia and in
      frontal areas. Thyroid and thyreotropinic function were normal. Testosterone
      levels were in the adult range, as well as basal and stimulated gonadotropin
      levels. Tanner stage P4, G4; testicular volume 12-15 mi. Molecular cytogenetics
      studies are now underway to further elucidate the etiology of this form of PHP.

PMID- 10969933
TI  - A patient with early puberty associated with Chiari 1 malformation.
AB  - A boy is described with early puberty and Chiari 1 malformation. It is not known
      whether there was an etiological relationship between these two conditions, or
      whether they were coincidental. This report emphasizes the utility of MRI when
      early puberty is diagnosed, particularly in males.

PMID- 10969934
TI  - Natural history of unruptured intracranial aneurysms: probability of and risk
      factors for aneurysm rupture.
AB  - OBJECT: The authors conducted a study to investigate the long-term natural
      history of unruptured intracranial aneurysms and the predictive risk factors
      determining subsequent rupture in a patient population in which surgical
      selection of cases was not performed. METHODS: One hundred forty-two patients
      with 181 unruptured aneurysms were followed from the 1950s until death or the
      occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual
      and cumulative incidence of aneurysm rupture as well as several potential risk
      factors predictive of rupture were studied using lifetable analyses and Cox's
      proportional hazards regression models including time-dependent covariates. The
      median follow-up time was 19.7 years (range 0.8-38.9 years). During 2575 person
      years of follow up, there were 33 first-time episodes of hemorrhage from
      previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17
      patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at
      10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of
      the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95%
      confidence interval [CI] 1-1.23, p = 0.05) and patient age at diagnosis inversely
      (RR 0.97 per year, 95% CI 0.93-1, p = 0.05) were significant independent
      predictors for a subsequent aneurysm rupture after adjustment for sex,
      hypertension, and aneurysm group. Active smoking status at the time of diagnosis
      was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04-2.06, p
      = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of
      hypertension, and aneurysm group. Active smoking status as a time-dependent
      covariate was an even more significant risk factor for aneurysm rupture (adjusted
      RR 3.04, 95% CI 1.21-7.66, p = 0.02). CONCLUSIONS: Cigarette smoking, size of the
      unruptured intracranial aneurysm, and age, inversely, are important factors
      determining risk for subsequent aneurysm rupture. The authors conclude that such
      unruptured aneurysms should be surgically treated regardless of their size and of
      a patient's smoking status, especially in young and middle-aged adults, if this
      is technically possible and if the patient's concurrent diseases are not
      contraindications. Cessation of smoking may also be a good alternative to surgery
      in older patients with small-sized aneurysms.

PMID- 10969935
TI  - The remodeling technique of balloon-assisted Guglielmi detachable coil placement
      in wide-necked aneurysms: experience at the University of Illinois at Chicago.
AB  - OBJECT: Reports in the literature have offered discussions of the feasibility,
      efficacy, and safety of balloon-assisted Guglielmi detachable coil (GDC)
      placement in wide-necked intracranial aneurysms, which was first described by
      Jacques Moret as the "remodeling technique." In this article the authors
      summarize their results in a subset of aneurysms treated with GDCs using the
      remodeling technique. METHODS: This report contains a retrospective analysis of
      72 patients with 75 aneurysms who underwent 79 endovascular procedures performed
      using the remodeling technique. Morphological outcome was determined at the end
      of each procedure and by reviewing available follow-up angiograms. Clinical
      assessments and outcomes are reported using a modified Glasgow Outcome Scale.
      Coils were placed in 66 (88%) of 75 aneurysms selected for treatment. In eight
      aneurysms (11%) treatment failures occurred due to the tortuosity of the vessel
      used to reach the aneurysms or because of balloon inadequacies. Incorporating all
      available follow-up data the authors found that 50 (78%) of 64 aneurysms were
      completely or subtotally (> 95%) occluded and eight (12%) of 64 were incompletely
      (< 95%) occluded. Since the time of coil placement, eight aneurysms have
      progressed to complete occlusion and another five have exhibited progressive
      thrombosis on follow-up angiograms. In three aneurysms there has been neck
      remnant growth. Surgical clipping was performed to treat six aneurysms after an
      initial coil placement procedure. Permanent incidences of morbidity were limited
      to four patients and there were three deaths directly related to the procedure.
      CONCLUSIONS: The remodeling technique shows promise in increasing the number of
      cerebral aneurysms amenable to treatment by endovascular coil placement, and
      offers an alternative approach to aneurysms that have met with failed surgical
      treatment or are surgically inaccessible. Long-term follow-up review is needed to
      determine the final outcome of aneurysms treated by this technique.

PMID- 10969936
TI  - Effect of direct arterial bypass on the prevention of future stroke in patients
      with the hemorrhagic variety of moyamoya disease.
AB  - OBJECT: The authors evaluated the effects of superficial temporal artery-middle
      cerebral artery (STA-MCA) bypass in the prevention of future stroke, including
      rebleeding or an ischemic event, in patients suffering from hemorrhagic moyamoya
      disease by comparing this method with indirect bypass and conservative treatment.
      METHODS: Twenty-two patients who had hemorrhagic moyamoya disease but no aneurysm
      comprised the study group. These patients' clinical charts were examined with
      respect to their treatment and clinical course after an initial hemorrhagic
      episode. The mean age of the patients was 43 years and the follow-up period
      ranged from 0.8 to 15.1 years, with a mean of 8 years. Eleven patients (50%) were
      conservatively treated. Among the 11 patients who were surgically treated, STA
      MCA bypass was performed in six patients (27%) and
      encephaloduroarteriosynangiosis (EDAS) in the other five patients (23%). Nine
      patients (41%) presented with an ischemic or rebleeding event during the follow
      up period. The incidence of future stroke events in patients who had undergone an
      STA-MCA bypass was significantly lower (p<0.05) than that in patients who had
      been treated conservatively or with EDAS. Kaplan-Meier plots comparing stroke
      free times in patients treated with direct bypass and those in patients who
      conservatively or with indirect bypass showed a significant difference (p<0.05)
      in favor of direct bypass. CONCLUSIONS: The effect of STA-MCA bypass on the
      prevention of recurrent hemorrhage or an ischemic event in patients with
      hemorrhagic moyamoya disease has been statistically confirmed in this study.

PMID- 10969937
TI  - Transparahippocampal selective amygdalohippocampectomy in children and
      adolescents: efficacy of the procedure and cognitive morbidity in patients.
AB  - OBJECT: Unilateral resection of the hippocampus and amygdala can be used to treat
      medically intractable mesial temporal lobe seizures. To date seizure outcome and
      the extent of cognitive morbidity have been unknown in children following the
      transparahippocampal variation of selective amygdalohippocampectomy (TSA), which
      prompted the present prospective study. METHODS: Preoperative examinations and
      outcomes in 22 consecutive children and adolescents who underwent TSA were
      studied. Cognitive and psychological morbidity were assessed using standard
      neuropsychological instruments. The authors evaluated relationships between
      seizure control and cognitive morbidity and 13 and nine clinical variables,
      respectively. Seizure control was achieved in 11 (65%) of 17 patients (>2 years
      follow up). Among 13 clinical variables, the only preoperative finding that had a
      significant bearing on seizure control was the presence of unilateral
      hypometabolism, which could be observed on [18F]fluorodeoxyglucose-positron
      emission tomography scans (p<0.001). Patients with seizure control showed
      significant improvements in verbal and full scale intelligence quotients (both p
      = 0.05). Patients with longer preoperative durations of seizures exhibited more
      cognitive impairment that persisted postoperatively. Cognitive outcome analysis
      based on nine clinical factors revealed no significant difference in cognitive
      parameters postoperatively, except that significant improvement occurred in rote
      verbal memory scores among patients who underwent right-sided TSA (p = 0.01).
      Individually, 81% of the children achieved significant improvement in at least
      one of seven cognitive parameters, and 52% had stable or improved scores in all
      parameters. CONCLUSIONS: The results indicate that TSA is a safe effective
      approach for the treatment of medically intractable mesial temporal lobe seizures
      in children with minimum effect on cognitive morbidity. Given that the literature
      suggests that children suffer progressive cognitive morbidity from persistent
      seizures, the results of this study support early surgical intervention for this
      group of children.

PMID- 10969938
TI  - Predictors of neuropsychological outcome in patients following microelectrode
      guided pallidotomy for Parkinson's disease.
AB  - OBJECT: The authors studied neuropsychological performance following
      microelectrode-guided posteroventral pallidotomy in patients with Parkinson's
      disease (PD) and evaluated correlations with presurgical and surgical factors.
      METHODS: Neuropsychological changes 3 months (43 patients) and 12 months (27
      patients) after microelectrode-guided pallidotomy for PD are reported in a series
      of 44 consecutive patients with the disease, who improved neurologically, as
      measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in both the
      "off' (p<0.001) and best "on" (p<0.001) states. Findings of the vocabulary
      subtest of the Wechsler Adult Intelligence Scale-Revised (p<0.01), Letter Fluency
      (p<0.001), Verbal Fluency for semantic categories (p<0.001), and the Wisconsin
      Card Sorting Test (p<0.01) showed a significant decline in neuropsychological
      performance in patients 3 months after undergoing left-sided pallidotomy.
      Impairment in the language domain (semantic fluency) persisted at the 12-month
      follow-up examination (p<0.01). Visual memory improved after right-sided
      pallidotomies (p<0.01 after 3 months), with a nonsignificant trend toward
      persistent improvement 1 year postsurgery (p<0.02 after 12 months). Preoperative
      semantic fluency was influenced by patient age (p<0.001) and by the width of the
      third ventricle (p<0.05), as measured by magnetic resonance imaging. A regression
      model revealed that semantic fluency 3 months postoperatively was significantly
      affected by the baseline score (p<0.001), side of surgery (p<0.001), handedness
      (p<0.01), and patient age (p<0.05). However, postoperative lesion volume, lesion
      location, number of tracks, number of lesions, distance from anatomical
      landmarks, or UPDRS score did not significantly contribute to neuropsychological
      outcome. CONCLUSIONS: Neuropsychological changes in a cohort of patients with PD
      who underwent pallidotomy and experienced excellent clinical benefits and minimum
      postoperative complications, emphasize the importance of neuropsychological
      examinations and further investigation of predictive factors.

PMID- 10969939
TI  - Microvascular decompression for cochlear symptoms.
AB  - OBJECT: The object of this study was to evaluate the efficacy of a new
      neurovascular decompression technique in relieving symptoms of cochlear nerve
      dysfunction. METHODS: Nineteen patients with slowly progressive hearing loss, low
      frequency fluctuating hearing loss, and high-pitched tinnitus due to
      neurovascular compression (NVC) of the eighth cranial nerve in a triangular space
      between the seventh and eighth cranial nerves (the VII-VIII triangle) of the
      cerebellopontine angle (CPA) were treated using a new technique for microvascular
      decompression that was developed by anatomical study in 24 cadaver specimens of
      the CPA. In 12 of 19 patients the anterior inferior cerebellar artery (AICA) was
      observed to cause compression in the VII-VIII triangle and this vessel was easily
      mobilized medially for placement of a silicone sponge or Teflon cushion between
      the compressing artery and nerve. Postoperatively, hearing loss of 20 dB or more
      that was present in 11 of the 19 patients with NVC improved by more than 5 dB in
      seven (64%), including the patient with the most severe hearing loss. Of 18
      patients presenting with tinnitus preoperatively, eight (44%) had no tinnitus and
      an additional nine (for a total of 94%) had good improvement in tinnitus after
      surgery and at long-term follow up. CONCLUSIONS: The microvascular decompression
      technique described is highly successful in treating symptoms due to direct or
      indirect compression of the cochlear nerve, with minimal risk of complications.
      Recordings of auditory brainstem responses confirmed the clinical diagnosis of
      NVC of the eighth cranial nerve and correlated with clinical results after
      microvascular decompression of the cochlear nerve.

PMID- 10969940
TI  - Role of the mode of sensory stimulation in presurgical brain mapping in which
      functional magnetic resonance imaging is used.
AB  - OBJECT: The aim of this study was to evaluate different types of sensory
      stimulation used to distinguish between microvasculature and venous drainage on
      functional magnetic resonance (fMR) images with blood oxygen level-dependent
      (BOLD) contrast. METHODS: Seven volunteers received three sensory stimulations.
      One consisted of small discontinuous automated pokes to the ventral aspect of the
      right thumbtip. The other two were delivered by the investigator, who vigorously
      brushed the ventral aspect of the right thumbtip either alone or in combination
      with the thenar region. Seven contiguous axial slices of the head were acquired
      using echoplanar fMR imaging during each mode of stimulation. Boxcar analysis and
      Student's t-test were performed. Cluster analysis was used to determine
      significant differences between rest and activation phases. The major findings
      were 1) that a discontinuous sensory stimulation involving a small skin area was
      able to evoke a limited activated area in the postcentral gyrus with a low
      activation index (AI [2%]); 2) that this limited activated area was included in
      the activated area elicited by the continuous sensory stimulations; and 3) that
      this also evoked multiple activated areas exhibiting AIs of either approximately
      2% or greater than 5%. This indicated that the limited discontinuous tactile
      stimulation evoked a BOLD-contrast fMR image essentially of microvasculature,
      whereas the more extensive continuous stimulations evoked a BOLD-contrast fMR
      image in both microvasculature and venous drainage. CONCLUSIONS: Different
      sensory stimulations are necessary to differentiate primary sensory cortex from
      venous drainage for presurgical brain mapping.

PMID- 10969941
TI  - Mobile computerized tomography scanning in the neurosurgery intensive care unit:
      increase in patient safety and reduction of staff workload.
AB  - OBJECT: Transportation of unstable neurosurgical patients involves risks that may
      lead to further deterioration and secondary brain injury from perturbations in
      physiological parameters. Mobile computerized tomography (CT) head scanning in
      the neurosurgery intensive care (NICU) is a new technique that minimizes the need
      to transport unstable patients. The authors have been using this device since
      June 1997 and have developed their own method of scanning such patients. METHODS:
      The scanning procedure and radiation safety measures are described. The
      complications that occurred in 89 patients during transportation and conventional
      head CT scanning at the Department of Radiology were studied prospectively. These
      complications were compared with the ones that occurred during mobile CT scanning
      in 50 patients in the NICU. The duration of the procedures was recorded, and an
      estimation of the staff workload was made. Two patient groups, defined as high-
      and medium-risk cases, were studied. Medical and/or technical complications
      occurred during conventional CT scanning in 25% and 20% of the patients in the
      high- and medium-risk groups, respectively. During mobile CT scanning
      complications occurred in 4.3% of the high-risk group and 0% of the medium-risk
      group. Mobile CT scanning also took significantly less time, and the estimated
      personnel cost was reduced. CONCLUSIONS: Mobile CT scanning in the NICU is safe.
      It minimizes the risk of physiological deterioration and technical mishaps linked
      to intrahospital transport, which may aggravate secondary brain injury. The time
      that patients have to remain outside the controlled environment of the NICU is
      minimized, and the staff's workload is decreased.

PMID- 10969942
TI  - Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive
      neuroectodermal tumors by using conventional banding, comparative genomic
      hybridization, and spectral karyotyping.
AB  - OBJECT: Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of
      the central nervous system are malignant, invasive embryonal tumors with
      predominantly neuronal differentiation that comprise 20% of pediatric brain
      tumors. Cytogenetic analysis has shown that alterations in chromosome 17,
      particularly the loss of 17p and the formation of isochromosome 17q, as well as
      the gain of chromosome 7 are the most common changes among this group of tumors.
      Comparative genomic hybridization (CGH) studies have largely confirmed these
      cytogenetic findings and have also identified novel regions of gain, loss, and
      amplification. The advent of more sophisticated multicolored fluorescence in situ
      hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits
      complete recognition of all aberrations including extremely complex
      rearrangements. The authors report a retrospective analysis of 19 medulloblastoma
      and five PNET cases studied using combinations of classic banding analysis, FISH,
      CGH, and SKY to examine comprehensively the chromosomal aberrations present in
      this tumor group and to attempt to identify common structural rearrangement(s).
      METHODS: The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the
      tumors studied, which confirms data reported in the current literature. However,
      the authors have also combined the results of all three molecular cytogenetic
      assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal
      rearrangement (gained, lost, or involved in structural rearrangement).
      CONCLUSIONS: The combined results indicate that chromosomes 7 and 17 are the most
      frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all
      rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%),
      and 22 (6.5%) were also found to be frequently rearranged, followed by
      chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors
      exhibited high-level gains or gene amplification. Amplification of MYCN was
      identified in four tumors, whereas amplification of MYCC was identified in one
      tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally,
      desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher
      karyotype heterogeneity, amplification, and aneusomy than classic
      medulloblastomas.

PMID- 10969943
TI  - Hypoxia in a human intracerebral glioma model.
AB  - OBJECT: The development of hypoxia in human gliomas is closely related to
      functional vasculature and the presence of hypoxia has important biological and
      therapeutic consequences. Assessment of hypoxia is necessary to understand its
      role in treatment response and to evaluate treatment strategies to improve tumor
      oxygenation. In this study, the authors report findings of their analysis of the
      degree of hypoxia in relation to other vascular parameters in a human
      intracerebral glioma xenograft. METHODS: In sections of tumor, hypoxic regions
      were identified immunohistochemically by using the hypoxic marker pimonidazole.
      The S-phase marker bromodeoxyuridine was used to detect cell proliferation, and
      the perfusion marker Hoechst 33342 was used to delineate perfused vessels.
      Vascular structures were stained with an endothelial marker. Hypoxic tumor
      regions were clearly present in this human intracerebral glioma model. Hypoxic
      areas were usually found in nonperfused regions, whereas tumor cell proliferation
      was especially marked in perfused tumor areas. Furthermore, by using in situ
      hybridization the authors identified infiltrating tumor cells in the normal
      brain. This feature is often observed in gliomas in patients. CONCLUSIONS: This
      model is a representative human glioma model that provides the researcher with
      the opportunity to analyze the relationship between the degree of hypoxia and
      vascular parameters, as well as to examine the effects of treatments aimed at
      modification of the oxygenation status of a tumor.

PMID- 10969944
TI  - Maturation-dependent response of the piglet brain to scaled cortical impact.
AB  - OBJECT: The goal of this study was to investigate the relationship between
      maturational stage and the brain's response to mechanical trauma in a
      gyrencephalic model of focal brain injury. Age-dependent differences in injury
      response might explain certain unique clinical syndromes seen in infants and
      young children and would determine whether specific therapies might be
      particularly effective or even counterproductive at different ages. METHODS: To
      deliver proportionally identical injury inputs to animals of different ages, the
      authors have developed a piglet model of focal contusion injury by using specific
      volumes of rapid cortical displacement that are precisely scaled to changes in
      size and dimensions of the growing brain. Using this model, the histological
      response to a scaled focal cortical impact was compared at 7 days after injury in
      piglets that were 5 days, 1 month, and 4 months of age at the time of trauma.
      Despite comparable injury inputs and stable physiological parameters, the
      percentage of hemisphere injured differed significantly among ages, with the
      youngest animals sustaining the smallest lesions (0.8%, 8.4%, and 21.5%, for 5
      day-, 1-month-, and 4-month-old animals, respectively, p = 0.0018). CONCLUSIONS:
      These results demonstrate that, for this particular focal injury type and
      severity, vulnerability to mechanical trauma increases progressively during
      maturation. Because of its developmental and morphological similarity to the
      human brain, the piglet brain provides distinct advantages in modeling age
      specific responses to mechanical trauma. Differences in pathways leading to cell
      death or repair may be relevant to designing therapies appropriate for patients
      of different ages.

PMID- 10969945
TI  - Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries.
AB  - OBJECT: It is not known whether the factors responsible for vasospasm after
      subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed
      independent of the subarachnoid blood clot or whether the continued presence of
      clot is required for the entire time of vasospasm. The authors undertook the
      present study to investigate this issue. METHODS: To distinguish between these
      possibilities, bilateral SAH was induced in monkeys. The diameters of the
      monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the
      day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed
      surgically on Day 1, 3, or 5 or, in control animals, was not removed until the
      animals were killed on Day 7 or 9. The concentrations of hemoglobins and
      adenosine triphosphate (ATP), substances believed to cause vasospasm, were
      measured in the removed clots and the contractile activity of the clots was
      measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days
      after placement, vasospasm was significantly diminished 4 days after clot
      removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a
      significant decrease over time in hemoglobin and ATP concentrations and in the
      contractile activity of the clots, although substantial hemoglobin and
      contractile activity was still present on Day 7. CONCLUSIONS: The authors infer
      from these results that vasospasm requires the presence of subarachnoid blood for
      at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid
      blood clot. Because the clot still contains substantial amounts of hemoglobin and
      contractile activity after 5 days, there may be an adaptive response in the
      cerebral arteries that allows them to relax in the presence of the stimulus that
      earlier caused contraction.

PMID- 10969946
TI  - Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a
      rat model of subarachnoid hemorrhage.
AB  - OBJECT: Rho A, a small guanosine triphosphate-binding protein, and rho kinases
      have been suggested to play an important role in the agonist-induced myofilament
      Ca++ sensitization and cytoskeletal organization of smooth-muscle cells. To
      discover their possible roles in the prolonged contraction seen in cerebral
      vasospasm, the authors investigated the messenger (m)RNA expressions of rho A and
      rho-associated kinases alpha and beta in the basilar artery (BA) of a rat double
      cisternal blood-injection model. METHODS: An experimental subarachnoid hemorrhage
      (SAH) was achieved in rats by twice injecting autologous arterial blood into the
      cisterna magna of each animal. The mRNAs for rho A and rho-associated kinases
      alpha and beta of the rat BA were analyzed using reverse transcription-polymerase
      chain reaction (RT-PCR). The cisternal blood injection induced a marked
      corrugation of elastic lamina and contraction of smooth-muscle cells observed
      with the aid of light and transmission electron microscopy in the rat BA on Days
      3, 5, and 7. Results of the RT-PCR revealed that mRNAs for rho A and rho kinases
      alpha and beta were expressed in the rat BA and that they were significantly
      upregulated and reached their peaks on Day 5. CONCLUSIONS: The mRNA upregulation
      of these proteins indicates that activation of rho A/rho kinase-related signal
      transduction pathways is involved in the development of long-lasting contraction
      of cerebral arteries after SAH.

PMID- 10969948
TI  - An unusual pterygopalatine meningocele associated with neurofibromatosis type 1.
      Case report.
AB  - The authors describe an unusual meningocele of the lateral wall of the cavernous
      sinus and the anterior skull base in a young patient with typical stigmata of
      neurofibromatosis Type 1 (NF1). This lesion was discovered during evaluation for
      recurrent meningitis. It represented an anterior continuation of Meckel's cave
      into a large cerebrospinal fluid space within the lateral wall of the cavernous
      sinus, extending extracranially through an enlarged superior orbital fissure into
      the pterygopalatine fossa adjacent to the nasal cavity. It was successfully
      obliterated, via an intradural middle fossa approach, with fat packing and
      fenestration into the subarachnoid space. This meningocele most likely represents
      a variant of cranial nerve dural ectasia occasionally seen in individuals with
      NF1. It has as its basis the same mesodermal defect responsible for the more
      common sphenoid wing dysplasia and spinal dural ectasias identified with this
      condition. Involvement of the trigeminal nerve with expansion of the lateral wall
      of cavernous sinus has not been reported previously. The authors surmise,
      however, that it may be present in some cases of orbital meningocele associated
      with sphenoid wing dysplasia.

PMID- 10969947
TI  - Brain abscess related to metal fragments 47 years after head injury. Case report.
AB  - The authors report a case of symptomatic brain abscess in a 51-year-old man who
      presented with personality changes and generalized seizures. He had survived a
      grenade explosion injury during the Korean War 47 years previously. Computerized
      tomography scanning revealed multiple conglomerate rim-enhancing lesions and
      metallic foreign bodies in the right frontal lobe. The mass was totally removed
      and Pseudomonas aeruginosa was isolated from microbial cultures. Retained foreign
      bodies in the brain, whether bone or metal, should be removed at the time of
      injury if at all possible. If this cannot be accomplished, patients with such
      retained foreign bodies should be carefully monitored for life.

PMID- 10969949
TI  - Involution of diencephalic pilocytic astrocytoma after partial resection. Report
      of two cases in adults.
AB  - Spontaneous involution of pilocytic astrocytoma has been reported in children,
      particularly in those with neurofibromatosis Type 1. However, this rare
      occurrence has not been documented in adults. In this report the authors describe
      two cases of adults with pilocytic astrocytoma. One patient had a tumor in the
      thalamus and the other in the hypothalamus and optic chiasm; both patients
      underwent partial resection of the tumor. The initial magnetic resonance (MR)
      images demonstrated reduction in size of the tumors, and subsequent MR images
      obtained several months later revealed marked further involution with reduction
      in size and enhancement. The possible mechanisms for this uncommon occurrence are
      discussed.

PMID- 10969950
TI  - Dysembryoplastic neuroepithelial tumor of the cerebellum and brainstem. Case
      report.
AB  - The authors present a case in which dysembryoplastic neuroepithelial tumors
      (DNETs) occurred in the cerebellum and brainstem of a 44-year-old woman. A
      magnetic resonance image of the brain revealed multiple cystic lesions in the
      right cerebellar hemisphere, vermis, tonsil, and brainstem. Partial removal of
      the tumors was performed. There were gray multinodular gelatinous lesions on the
      cerebellar hemisphere. Histologically, the tumors exhibited areas of multiple
      microcystic nodules in the cerebellar white matter, which were composed of
      oligodendroglia-like cells (OLCs), astrocytes, and neurons. There were multiple,
      variable nodules in the lesions, lined by OLCs. The adjacent cerebellar cortex
      displayed dysplastic features. Reduction of granule neurons and dislocation of
      Purkinje cells into the molecular layer were observed. The pathological profile
      of this patient agrees with that described by Daumas-Duport, et al., as a
      "dysembryoplastic neuroepithelial tumor."

PMID- 10969951
TI  - Metastatic solitary fibrous tumor of the meninges. Case report.
AB  - Solitary fibrous tumor (SFT) is a unique tumor composed of interstitial dendritic
      cells that was first described in the thorax and subsequently reported in diverse
      organs. Extrathoracic SFTs are predominantly benign but rare malignant cases have
      been documented. In the nervous system, SFT has been described as a meningeal
      lesion although all 14 previously reported cases were benign. The authors report
      the first case of a meningeal SFT occurring in a 55-year-old woman. The tumor
      first presented as a meningeal lesion that after three recurrences over a 10-year
      period metastasized to the soft tissues and lungs. The potentially malignant
      nature of cranial SFTs, especially those with atypical histological features and
      high mitotic counts, should be recognized.

PMID- 10969952
TI  - Extracorporeal irradiation of tumorous calvaria. Case report.
AB  - This patient with recurrent meningioma grossly involving the frontal bone
      underwent craniotomy and tumor resection. During the procedure a bone flap was
      irradiated extracorporeally at a very high dose (120 Gy) sufficient to sterilize
      residual tumor cells, and the bone was then successfully replaced orthotopically
      for reconstruction. The use of autologous irradiated bone in this setting offers
      advantages over cadaveric transplantation and prosthetic implants. Radiation
      might cause less disruption of the bone's architecture than other techniques of
      tumor cell eradication.

PMID- 10969953
TI  - Use of an intracranial near-infrared probe for localization during stereotactic
      surgery for movement disorders.
AB  - Localization of targets during stereotactic surgery is frequently accomplished by
      identification of the boundaries between the gray matter of various nuclei and
      the surrounding white matter. The authors describe an intracranial probe
      developed for this purpose, which uses near-infrared (NIR) light. The probe fits
      through standard stereotactic holders and emits light at its tip. The scattered
      light is detected and analyzed by a spectrometer, with the slope of the trailing
      portion of the reflectance curve used as the measurement value. Near-infrared
      readings were obtained during 27 neurosurgical procedures. The first three
      operations were temporal lobectomies, with values obtained from tracks in the
      resected specimen and resection bed. In the next five procedures, the probe was
      inserted stereotactically to a depth of 1 to 2 cm with measurements obtained
      every 1 mm. The probe was then used in 19 stereotactic procedures for movement
      disorders, obtaining measurements every 0.5 to 1 mm to target depths of 6 to 8 cm
      to interrogate subcortical structures. The NIR signals were correlated to
      distances beneath the cortical surface measured on postoperative computerized
      tomography or magnetic resonance imaging by using angle correction and three
      dimensional reconstruction techniques. The NIR values for white and gray matter
      obtained during the lobectomies were significantly different (white matter 2.5+/
      0.37, gray matter 0.82+/-0.23 mean +/- standard deviation). The NIR values from
      the superficial stereotactic tracks showed initial low values corresponding to
      cortical gray matter and high values corresponding to subcortical white matter.
      There was good correlation between the NIR signals and postoperative imaging in
      the 19 stereotactic cases. Dips due to adjacent sulci, a plateau of high signal
      due to subcortical white matter, a dip in the NIR signal during passage through
      the ventricle, dips due to the caudate nucleus, and peaks due to the white matter
      capsule between ventricle and thalamus were constant features. The putamen
      capsule boundary and the lamina externa and interna of the globus pallidus could
      be distinguished in three cases. Elevated signals corresponding to the thalamic
      floor were seen in 10 cases. Nuances such as prior lesions and nonspecific white
      matter changes were also detected. There was no incidence of morbidity associated
      with use of the probe. Data acquisition was straightforward and the equipment
      required for the studies was inexpensive. The NIR probe described in this article
      seems to be able to detect gray-white matter boundaries around and within
      subcortical structures commonly encountered in stereotactic functional
      neurosurgery. This simple, inexpensive method deserves further study to establish
      its efficacy for stereotactic localization.

PMID- 10969954
TI  - A newly designed key-hole button.
AB  - Patients who have undergone frontotemporal craniotomy occasionally complain of
      scalp deformity in the anterior temporal area. This occurs as a result of
      inappropriate reconstruction of the temporal muscle and repair of the bone defect
      at the key hole and surrounding skull. Although several methods have been
      developed to prevent skin indentation on burr holes located over the convexity,
      satisfactory cosmetic repair of the key hole remains difficult because of its
      complicated bone curvature. To prevent such postoperative deformity, the authors
      designed a button made of hydroxyapatite ceramics to fit the key hole easily.
      This new, biocompatible "key-hole button" is shaped to alleviate the deformity of
      the temple by filling the bone defect in a more natural way. The specifications
      of this device and its clinical application are described.

PMID- 10969955
TI  - A new device for endoscopic third ventriculostomy.
AB  - Since its description by Dandy in 1922, several techniques have been used to
      perform third ventriculostomy under endoscopic control. Except for the blunt
      technique, in which the endoscope is used by itself to create the opening in the
      floor of the third ventricle, the other techniques require more than one
      instrument to perforate the floor of the ventricle and enlarge the
      ventriculostomy. The new device described is a sterilizable modified forceps that
      allows both the opening of the floor and the enlargement of the ventriculostomy
      in a simple and effective way. The new device has the following characteristics:
      1) the tip of the forceps is thin enough to allow the easy perforation of the
      floor of the ventricle; 2) the inner surface of the jaws is smooth to avoid
      catching vessels of the basal cistern; and 3) the outer surface of the jaws has
      indentations that catch the edges of the opening to prevent them from slipping
      along the instrument's jaws. The ventricle floor is opened by gentle pressure of
      the forceps, which is slowly opened so that the edges of the aperture are caught
      by the distal outer indentation of the jaws, leading to an approximately 4-mm
      opening of the floor. This device has been used successfully in 10 consecutive
      patients. This new device allows surgeons to perform third ventriculostomy under
      endoscopic control in a very simple, quick, and effective way, avoiding the need
      for additional single-use instruments.

PMID- 10969956
TI  - Clival encephalocele.

PMID- 10969957
TI  - Neuronal hamartoma of the trigeminal sensory root associated with trigeminal
      neuralgia.

PMID- 10969958
TI  - Superior petrosal vein varicosity presenting as an enhancing cerebellopontine
      angle lesion.

PMID- 10969959
TI  - Predominant infraspinatus muscle weakness in suprascapular nerve compression.

PMID- 10969960
TI  - Prediction of aneurysm rupture site by an angiographically identified bleb at the
      aneurysm neck.

PMID- 10969961
TI  - Biographical sketch of Kenneth G. McKenzie (1892-1964).
AB  - This article is an expanded version of the opening address Dr. Morley delivered
      at a University of Toronto symposium, "Seventy-Five Years of Neurosurgery in
      Canada," celebrating the 75th Anniversary of the appointment of Kenneth G.
      McKenzie, Canada's first career neurosurgeon, to the University of Toronto and
      the Toronto General Hospital in 1923. Kenneth G. McKenzie (1892-1964) was the
      first surgeon in Canada to limit his practice to neurosurgery. This article
      contains a brief biographical study of the man, his upbringing, and management of
      his professional life at Toronto General Hospital. Some of his published
      neurosurgical articles are also reviewed.

PMID- 10969962
TI  - Pallidotomy and neuropsychological outcome.

PMID- 10969963
TI  - Tumor shape and recurrence.

PMID- 10969964
TI  - Progesterone regulators.

PMID- 10969965
TI  - Segmental neurofibromatosis.

PMID- 10969966
TI  - Combinatorial approach to lead optimization of a novel hexapeptide with
      antifungal activity.
AB  - Three sets of sublibraries of an antifungal lead peptide His-D-Trp-D-Phe-Phe-D
      Phe-Lys-NH2 (I) have been prepared by introducing variations at positions 1, 4
      and 6. They were screened for their antifungal activity against C. albicans and
      C. neoformans in order to quantify inhibition at each step of the hexapeptide
      sublibrary iteration. The studies led to the identification of Arg-D-Trp-D-Phe
      Ile-D-Phe-His-NH2 as a novel hexapeptide with potent antifungal activity against
      both C. albicans and C. neoformans.

PMID- 10969967
TI  - Synthesis and monoamine transporter affinity of 2beta-carbomethoxy-3beta-(2''-,
      3''- or 4''-substituted) biphenyltropanes.
AB  - A series of 11 novel 3beta-substituted biphenyltropanes was synthesized and
      evaluated by selective radioligand binding assays for affinity to monoamine
      transporters. Both 5-HTT potency and selectivity for 5-HTT over DAT was greatest
      with electron withdrawing group at the 3''-position.

PMID- 10969968
TI  - Identification of thioether intermediates in the reductive transformation of
      gonyautoxins into saxitoxins by thiols.
AB  - O-Sulfate group of gonyautoxin I and IV is transformed into methylene to form
      neosaxitoxin by thiols such as glutathione, a common cellular scavenger, in mild
      conditions. We isolated the intermediate of this conversion and propose that this
      reaction proceeds through formation of thiohemiketal, 1,2 shift to form stable
      thioether intermediate, and then redox exchange at sulfur atom to form the final
      product.

PMID- 10969969
TI  - Effects of 2-(substituted-sulfanyl)-3,5-dihydro-imidazole-4-one and 2
      (substituted-sulfanyl)-1H-imidazole-4,5-dione derivatives on serum HDL
      cholesterol.
AB  - A series of 2-substituted sulfanyl-3,5-dihydro-imidazole-4-ones and 2-substituted
      sulfanyl-1H-imidazole-4,5-diones was prepared and shown to increase high density
      lipoprotein cholesterol over other lipid fractions. Compound 1f showed efficacy
      in additional animal models. The major metabolite of 1f was isolated and its
      synthesis is reported. The effects of the metabolite on the lipid profile in rats
      were investigated.

PMID- 10969970
TI  - Synthesis and properties of 2'-O-methyl-2-thiouridine and oligoribonucleotides
      containing 2'-O-methyl-2-thiouridine.
AB  - A new method for the synthesis of 2'-O-methyl-2-thiouridine (s2Um) found in
      thermophilic bacterial tRNA was developed. Structural properties of s2Um and
      s2Um(p)U were studied by using 1H NMR spectroscopy. A modified nonaribonucleotide
      (RNA*: 5'-CGUUs2UmUUGC-3') was synthesized to study the base-recognition ability
      of s2Um in formation of RNA-RNA and RNA DNA duplexes. The UV melting experiments
      revealed that RNA*-RNA and RNA*-DNA duplexes having an s2U-A base pair are more
      stable than those having a U-A base pair. On the contrary, the thermal stability
      of RNA*-RNA and RNA*-DNA duplexes having an s2U-G wobble base pair was much lower
      than that of the unmodified duplexes having a natural U-G base pair. It is
      concluded that s2Um has higher selectivity toward A over G than unmodified U.

PMID- 10969971
TI  - The total synthesis of piclavines A1-4 and their biological evaluation.
AB  - The total synthesis of piclavines A1, A2, A3, and A4 has been achieved starting
      from compound 10 with enantiomeric enhancement. Their biological activities
      (antibacterial, antimicrobacterial, and antiviral activities and inhibition of
      cell growth) were evaluated.

PMID- 10969972
TI  - CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead
      compound.
AB  - A weak HTS hit at the CCR2B receptor has been converted into a potent antagonist
      by array SAR studies. Selectivity over the closely related CCR5 receptor is also
      achieved.

PMID- 10969973
TI  - 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists.
AB  - Twenty-four 4-alkylidene glutamic acids were synthesised and tested as potential
      subtype selective GluR5 and 6 ligands. It was found that a critical size of
      alkylidene group gave potent and selective GluR5 receptor agonists. LY339624 had
      Kis of 0.0326 and >100 microM on GluR5 and 6 receptors, respectively.

PMID- 10969975
TI  - A concise synthesis of photoactivatable 4-aroyl-L-phenylalanines.
AB  - An efficient preparation of the title compounds from 4-iodo-L-phenylalanines
      using a carbonylative Stille cross-coupling reaction as the key-step is
      described.

PMID- 10969974
TI  - Inhibitors of bacterial tyrosyl tRNA synthetase: synthesis of four stereoisomeric
      analogues of the natural product SB-219383.
AB  - Synthetic analogues of the microbial metabolite SB-219383 have been synthesised
      with defined stereochemistry. Densely functionalised hydroxylamine containing
      amino acids were prepared by the addition of a glycine anion equivalent to sugar
      derived cyclic nitrones. One of four stereoisomeric dipeptides incorporating
      these novel amino acids was found to be a potent and selective inhibitor of
      bacterial tyrosyl tRNA synthetase, suggesting analogous stereochemistry of the
      natural product.

PMID- 10969976
TI  - Cinnamaldehydes inhibit cyclin dependent kinase 4/cyclin D1.
AB  - A series of cinnamaldehydes was synthesized for the study of inhibitory activity
      against cyclin dependent kinases (CDKs). A couple of compounds selectively
      inhibited cyclin D1-CDK4 with an IC50 value of 7-18 microM.

PMID- 10969977
TI  - Synthesis and biological property of carba and 20-deoxo analogues of arenastatin
      A.
AB  - The carba analogue, in which a methylene group is substituted for the oxygen atom
      linked to C-15, and 20-deoxo analogue of arenastatin A, a potent cytotoxic
      spongean depsipeptide, were synthesized. Both analogues lacking the 15,20-ester
      function, which was easily metabolized in serum, showed good stability in serum
      as well as moderate cytotoxic activity against KB cells and better solubility.

PMID- 10969978
TI  - A solid-phase synthesis for beta-turn mimetics of sialyl Lewis X.
AB  - A solid-phase synthesis of heterocyclic beta-turn mimetics of sialyl Lewis X,
      which is a natural carbohydrate ligand of selectins, was established. This
      synthetic method could be very useful for drug discovery of selectin antagonists
      using combinatorial chemistry techniques.

PMID- 10969979
TI  - Synthesis and evaluation of quinoline carboxyguanidines as antidiabetic agents.
AB  - The synthesis and in vivo activities of a series of substituted quinoline
      carboxyguanidines as a possible novel class of antidiabetic agents is described.

PMID- 10969980
TI  - Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen
      mustard.
AB  - A new glucuronylated prodrug of nornitrogen mustard, incorporating the same
      spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon
      exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower
      cytotoxicity against LoVo cancer cells is observed compared to the nornitrogen
      mustard alone. This is explained by cyclization of the intermediate carbamic acid
      to the inactive chloroethyl oxazolidinone.

PMID- 10969981
TI  - Synthesis of the nucleoside moiety of liposidomycins: elucidation of the
      pharmacophore of this family of MraY inhibitors.
AB  - Tunicamycins (TCMs) and liposidomycins (LPMs) are naturally occurring inhibitors
      of the bacterial translocase (MraY). Based on structure-activity relationship
      (SAR) studies, a molecular model has been proposed for their inhibitory
      mechanism. This study points out the importance of the nucleoside moiety of
      liposidomycins in the inhibition of MraY. A simplified molecule (I) based on the
      liposidomycin core structure has been synthesised and tested on MraY. The
      compound displayed a moderate inhibitory activity (IC50 = 50 microM). The
      validation of the molecular model was then performed by synthesising higher
      homologues of I, containing an additional stereocentre in the 5' position (XIV
      and XV). In agreement with the prediction, only the (S) isomer XV showed
      significant activity against MraY (IC50 = 5 microM).

PMID- 10969982
TI  - Effect of C2-exo unsaturation on the cytotoxicity and DNA-binding reactivity of
      pyrrolo[2,1-c][1,4]benzodiazepines.
AB  - A series of novel C2-exo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs)
      has been synthesised via a versatile pro-C2 ketone precursor. C2-exo-unsaturation
      enhances both DNA-binding reactivity and in vitro cytotoxic potency.

PMID- 10969983
TI  - Effect of C2/C3-endo unsaturation on the cytotoxicity and DNA-binding reactivity
      of pyrrolo[2,1-c][1,4]benzodiazepines.
AB  - A series of novel C2,C3-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines
      (PBDs) has been synthesised via cleavage of the N10-Alloc protecting group from
      appropriate precursors. Biophysical and biological evaluations show that the
      presence of C2/C3-endo unsaturation in the PBD C-ring enhances both DNA-binding
      reactivity and in vitro cytotoxic potency.

PMID- 10969984
TI  - Branched oligonucleotides containing bicyclic nucleotides as branching points and
      DNA or LNA as triplex forming branch.
AB  - Various Y-shaped branched oligonucleotides containing a 2'-0,3'-C-ethylene linked
      or 2'-0,4'-C-methylene linked bicyclic nucleotide as branching point were
      synthesized on an automated DNA synthesizer. Thermal denaturation experiments at
      260 and 284 nm showed increased thermal stabilities of complexes formed between
      these Y-shaped oligonucleotides and complementary DNA compared with those formed
      with the corresponding linear reference. The most significant effect was observed
      when LNA (locked nucleic acid) monomers were used in the triplex forming branch.

PMID- 10969985
TI  - A high-throughput screening utilizing intramolecular fluorescence resonance
      energy transfer for the discovery of the molecules that bind HIV-1 TAR RNA
      specifically.
AB  - A 16-residue peptide, including the Tat(49-57) sequence was labeled with a
      fluorescein and a tetramethylrhodamine at its N- and C-terminus, respectively.
      This double dye-labeled peptide was prepared as a tracer for high-throughput
      screening utilizing intramolecular fluorescence resonance energy transfer (FRET).
      The binding of the competitor molecules for HIV-1 TAR RNA were monitored and
      dissociation constants of those molecule were determined by using this tracer.
      This novel screening system might be useful to discover the drug for HIV-1 TAR
      RNA.

PMID- 10969986
TI  - 1-[2-[(Heteroaryloxy)heteroaryl]carbamoyl]indolines: novel and selective 5-HT2C
      receptor inverse agonists with potential as antidepressant/anxiolytic agents.
AB  - Bisaryl ethers have been identified with excellent 5-HT2C affinity and
      selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 11, 27 and
      38 have potent oral activity in a centrally mediated pharmacodynamic model of 5
      HT2C function and their potential as novel non-sedating anxiolytic and
      antidepressants is under investigation.

PMID- 10969987
TI  - 1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active
      5-HT2C receptor inverse agonists.
AB  - Bisarylmethoxyethers have been identified with nanomolar 5-HT2C affinity and
      selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 1, 2, 8, 12,
      14 and 18 have potent oral activity in a centrally mediated pharmacodynamic model
      of 5-HT2C function and their therapeutic potential is currently under further
      investigation.

PMID- 10969988
TI  - Aminoalkyl adenylate and aminoacyl sulfamate intermediate analogues differing
      greatly in affinity for their cognate Staphylococcus aureus aminoacyl tRNA
      synthetases.
AB  - Aminoalkyl adenylates and aminoacyl sulfamates derived from arginine, histidine
      and threonine, have been prepared and tested as inhibitors of their cognate
      Staphylococcus aureus aminoacyl tRNA synthetases. The arginyl derivatives were
      both potent nanomolar inhibitors of the Class I arginyl tRNA synthetase whereas
      for the Class II histidyl and threonyl tRNA synthetases, the acyl sulfamates were
      potent inhibitors but the adenylates had very little affinity.

PMID- 10969989
TI  - Discovery and synthesis of a potent sulfonamide ET(B) selective antagonist.
AB  - The synthesis and structure activity relationships of a series of sulfonamide
      endothelin antagonists are described. In the course of our modification studies,
      we discovered ET(B) selective antagonists. The most potent compound 15f displays
      IC50 values of 1.7 microM and 0.002 microM to ET(A) and ET(B) receptors,
      respectively.

PMID- 10969990
TI  - Synthesis and HIV-1 integrase inhibitory activities of caffeoylglucosides.
AB  - Caffeoylglucosides, which have a glucose ring as a central linker, were
      synthesized from methyl D-glucosides, and their anti-HIV-1 activities were
      tested. Among them, four dicaffeoylglucosides (IC50 = 29.1+/-35.1 microM), 6a,
      6b, 9b and 10b, showed HIV-1 integrase inhibitory activity as potent as L
      chicoric acid.

PMID- 10969991
TI  - Synthesis and preliminary biological evaluation of 4,6-disubstituted 3
      cyanopyridin-2(1H)-ones, a new class of calcium entry blockers.
AB  - The preparation of 3-cyano-4,6-diaryl-pyridin-2(1H)-ones 4a-h, calcium entry
      blockers related to diltiazem, is described starting from 1,3-diaryl-2-propen-1
      ones 5. On preliminary pharmacological tests all compounds are active and some of
      them show calcium antagonistic activity superior or comparable to diltiazem.

PMID- 10969992
TI  - Arylsulfonyl-N,N-diethyl-dithiocarbamates: a novel class of antitumor agents.
AB  - A series of alkyl/arylsulfonyl-N,N-diethyl-dithiocarbamates has been prepared by
      reaction of sodium N,N-diethyldithiocarbamate with alkyl/arylsulfonyl halides.
      The reactivity of these new derivatives against cysteine and glutathione has been
      investigated in order to identify derivatives that might label a critical
      cysteine residue of tubulin (Cys 239 of human beta2 tubulin chain). Some of the
      most reactive compounds showed moderate to powerful tumor growth inhibitory
      properties against several leukemia, non-small cell lung, ovarian, melanoma,
      colon, CNS, renal, prostate and breast cancer cell lines in vitro.

PMID- 10969993
TI  - 3-Phenyl-5-methyl-2H,5H-furan-2-ones: tuning antifungal activity by varying
      substituents on the phenyl ring.
AB  - A series of racemic 3-phenyl-5-methyl-2H,5H-furan-2-ones related to a natural
      product, (-)incrustoporine, was synthesized, and their antifungal activity
      evaluated. The key structural feature, furanone ring, was closed via H2SO4
      mediated cyclization of 2-phenylpent-4-enoic acids. The compounds displayed
      antifungal activity, especially against filamentous fungi. Expressed as the
      minimum inhibition concentration (MIC) in micromol/L, the activity of the most
      promising derivative against Absidia corymbifera matched that of ketoconazole
      (31.25 micromol/L). In terms of microg/mL, the substance was more active (7.6
      microg/mL) than this standard antifungal drug (16.6 microg/mL).

PMID- 10969994
TI  - Identification of early biomarkers of inflammation produced by keratinocytes
      exposed to jet fuels jet A, JP-8, and JP-8(100).
AB  - The purpose of this study was to identify biomarkers of inflammation in normal
      human epidermal keratinocytes (NHEK) exposed to three jet fuel mixtures, Jet A,
      JP8, and JP8(100). NHEK were treated over 24 hours with 0.1% jet fuels, and mRNA
      production and protein release of two proinflammatory cytokines, IL-8 and TNF
      alpha, were determined. Using an enzyme-linked immunosorbent assay (ELISA), NHEK
      were found to release both TNF-alpha and IL-8 in response to exposure to all
      three jet fuels. IL-8 release was noted within 8 hours and continued to rise
      through 24 hours compared to controls. Maximal levels of TNF-alpha release were
      seen at 4 hours and decreased in a time-dependent manner, although these levels
      remained above control levels at all time points assayed. mRNA for IL-8 was
      elevated 4 hours following exposure to the fuels, which was detected via a
      quantitative competitive reverse transcriptase-polymerase chain reaction (RT
      PCR). mRNA for TNF-alpha was detected at all time points assayed but was not
      quantified. These results demonstrate that jet fuels induce the production and
      release of proinflammatory cytokines in NHEK and thus create the potential for
      chronic inflammation, which may contribute to the development or progression of
      disease states in the skin.

PMID- 10969995
TI  - Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat
      brain and testis.
AB  - The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention
      by cotreatment with beta-carotene was investigated. Adult male rats were
      intragastrically administered 2 mg CdCl2/kg body weight three times a week
      intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid
      reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd
      administration, indicating increased lipid peroxidation (LPO) and oxidative
      stress. Cellular damage was indicated by inhibition of adenosine triphosphatase
      (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and
      testicular tissues. Chronic Cd administration resulted in a decline in
      glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and
      glutathione S-transferase (GST) activity in both organs. Administration of beta
      carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd-induced LPO. The
      brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were
      restored by beta-carotene cotreatment. Concurrent treatment with beta-carotene
      also ameliorated the decrease in ATPase activity and the increase in LDH activity
      in brain and testis of Cd-treated rats, indicating a prophylactic action of beta
      carotene on Cd toxicity. Therefore, the results indicate that the nutritional
      antioxidant beta-carotene ameliorated oxidative stress and the loss of cellular
      antioxidants and suggest that beta-carotene may control Cd-induced brain and
      testicular toxicity.

PMID- 10969996
TI  - Oxidation of thiodiglycol (2,2'-thiobis-ethanol) by alcohol dehydrogenase:
      comparison of human isoenzymes.
AB  - Sulfur mustard is a chemical warfare agent that causes blistering of the skin and
      damages the eyes and airway after environmental exposure. We have previously
      reported that thiodiglycol (TDG, 2,2'-bis-thiodiethanol), the hydrolysis product
      of sulfur mustard, is oxidized by alcohol dehydrogenase (ADH) purified from horse
      liver or present in mouse liver and human skin cytosol. Humans express four
      functional classes of ADH composed of several different isozymes, which vary in
      their tissue distribution, some occurring in skin. To help us evaluate the
      potential contribution of the various human isozymes toward toxicity in skin and
      in other tissues, we have compared the catalytic activity of purified human class
      I alphaalpha-, beta1beta1-, beta2beta2-, and gamma1gamma1-ADH, class II pi-ADH,
      class III chi-ADH, and class IV sigma-ADH with respect to TDG oxidation and their
      relative sensitivities to inhibition by pyrazole. Specific activities toward TDG
      were 123, 79, 347, 647, and 12 nmol/min/mg for the class I alphaalpha-,
      beta1,beta1-, beta2beta2-, and gamma1gamma1-ADH and class II pi-ADH,
      respectively. TDG was not a substrate for class III chi-ADH. The specific
      activity of class IV sigma-ADH was estimated at about 1630 nmol/min/mg. 1 mM
      pyrazole, a potent inhibitor of class I ADH, inhibited the class I alphaalpha,
      beta1beta1, beta2beta2, and gamma1gamma1 ADH and class IV sigma-ADH by 83, 100,
      56, 90, and 73%, respectively. The class I alphaalpha- and beta1beta1-ADH
      oxidized TDG with kcat/Km value of 7-8 mM(-1) min(-1), beta2beta2-ADH with a
      value 19 mM(-1) min(-1) and class I gamma1gamma1-ADH with a value of 176 mM(-1)
      min(-1). The kcat/Km value for class IV sigma-ADH was estimated at 4 mM(-1) min(
      1). The activities of class IV sigma-ADH and class I gamma1gamma1-ADH are of
      significant interest because of their prevalence in eyes, lungs, stomach, and
      skin, all target organs of sulfur mustard toxicity.

PMID- 10969997
TI  - Zymosan-induced changes in glucose release and fatty acid oxidation in the
      perfused rat liver.
AB  - The aim of the present study was to investigate the actions of zymosan on glucose
      release and fatty acid oxidation in perfused rat livers and to determine if
      Kupffer cells and Ca2+ ions are implicated in these actions. Zymosan caused
      stimulation of glycogenolysis in livers from fed rats. In livers from fasted rats
      zymosan caused gradual inhibition of glucose production and oxygen consumption
      from lactate plus pyruvate. Ketogenesis, oxygen consumption, and [14C-]-CO2
      production were inhibited by zymosan when the [1-14C]-palmitate was supplied
      exogenously. However, ketogenesis and oxygen consumption from endogenous sources
      were not inhibited. An interference with substrate-uptake by the liver may be the
      cause of the changes in gluconeogenesis and oxidation of fatty acids from
      exogenous sources. The pretreatment of the rats with gadolinium chloride and the
      removal of Ca2+ ions did not suppress the effects of zymosan on glucose release,
      a finding that argues against the participation of Kupffer cells or Ca2+ ions in
      the liver responses. The hepatic metabolic changes caused by zymosan could play a
      role in the systemic metabolic alterations reported to occur after in vivo
      zymosan administration.

PMID- 10969998
TI  - Transitory metabolic disruption and cytotoxicity elicited by benzo[a]pyrene in
      two cell lines from rainbow trout liver.
AB  - Two cell lines, RTL-W1 and R1, from rainbow trout liver were used to investigate
      the effects of benzo[A]pyrene (BaP). BaP induced a catalytic measure of CYP1A, 7
      ethoxyresorufin-O-deethylase (EROD) activity, in the rainbow trout liver cell
      line RTL-W1 but not in R1. Geldanamycin inhibited EROD induction by BaP.
      Potential BaP metabolites, BaP-7,8-dihydrodiol (BDP) and 6,12-BaP quinone (BQ)
      also induced EROD activity in RTL-W1. Very low BaP concentrations slightly
      stimulated cell proliferation in both cell lines. Higher BaP concentrations
      caused cytotoxicity in RTL-W1 but not in R1. Cytotoxicity was detected in a cell
      viability assay with 5-carboxyfluorescein diacetate acetoxymethyl ester, and as a
      decline in cell number. In both cell lines, BaP exposure impaired the reduction
      of the redox dye, alamar Blue (AB). After BaP removal, AB reduction recovered.
      Similar results were observed with BQ. As AB monitors metabolic activity, this
      novel phenomenon was termed transitory metabolic disruption. This decline in AB
      readings that was caused by BaP was ameliorated in RTL-W1 by alpha-naphthoflavone
      and geldanamycin, which suggests a role for CYP1A, and in R1 by indomethacin,
      which suggests involvement of prostaglandin-H-synthase. The significance of the
      response to BaP that is detected with AB and whether other PAHs cause it will be
      interesting future questions.

PMID- 10969999
TI  - Damage to DNA and activity of nuclear DNA repair and replicative enzymes
      following N-nitrosodiethylamine treatment to rats.
AB  - Continuous administration in the drinking water of hepatocarcinogen N
      nitrosodiethylamine (NDEA) to male rats (200 mg/L) for 60 days resulted in DNA
      damage in the form of single strand breaks. The damage, which is measured as a
      shift in the sedimentation of DNA in alkaline sucrose density gradients, was
      found to be maximum at the fourth week of treatment, and the sedimentation
      pattern of DNA was found to return to near normal size by the seventh week of
      NDEA treatment. Simultaneously, there were perturbations in the nuclear enzymes
      involved in DNA replication and repair. Activities of DNA polymerase beta, DNA
      ligase, and topoisomerase were found to increase in as early as the first week of
      NDEA treatment and reached the maximum at the fourth week, and thereafter
      declined to normal level by the eighth week of treatment. Concomitantly, the
      activities of DNA polymerase alpha, DNA primase, and RNA polymerase which were
      unaltered in the initial period of carcinogen treatment recorded a marked
      increase after sixth week of NDEA treatment. Results suggest that administration
      of NDEA inflicts DNA damage, which is manifested as increase in DNA repair
      enzymes in the initial period and activated DNA replicative enzymes at a later
      period, indicating the active proliferation of transformed cells.

PMID- 10970000
TI  - Identification of a possible association between carbon tetrachloride-induced
      hepatotoxicity and interleukin-8 expression.
AB  - Hepatotoxicants can elicit liver damage by various mechanisms that can result in
      cell necrosis and death. The changes induced by these compounds can vary from
      gross alterations in DNA repair mechanisms, protein synthesis, and apoptosis, to
      more discrete changes in oxidative damage and lipid peroxidation. However, little
      is known of the changes in gene expression that are fundamental to the mechanisms
      of hepatotoxicity. We have used DNA microarray technology to identify gene
      transcription associated with the toxicity caused by the hepatotoxicant carbon
      tetrachloride. Labeled poly A+ RNA from cultured human hepatoma cells (HepG2)
      exposed to carbon tetrachloride for 8 hours was hybridized to a human microarray
      filter. We found that 47 different genes were either upregulated or downregulated
      more than 2-fold by the hepatotoxicant compared with dimethyl formamide, a
      chemical that does not cause liver cell damage. The proinflammatory cytokine
      interleukin-8 (IL-8) was upregulated over 7-fold compared with control on the
      array, and this was subsequently confirmed at 1 hour and 8 hours by Northern blot
      analyses. We also found that carbon tetrachloride caused a time-dependent
      increase in interleukin-8 protein release in HepG2 cells, which was paralleled by
      a decrease in cell viability. These data demonstrate that carbon tetrachloride
      causes a rapid increase in IL-8 mRNA expression in HepG2 cells and that this
      increase correlates with a later and significant increase in the levels of
      interleukin-8 protein. These results illustrate the potential of microarray
      technology in the identification of novel gene changes associated with toxic
      processes.

PMID- 10970001
TI  - New perspectives in the evidence-based healthcare debate.

PMID- 10970002
TI  - Evidence-based medicine: the need for a new definition.
AB  - Evidence is defined by its ability to establish or support conclusions. Evidence
      based medicine (EBM) equates evidence with scientific evidence and views factors
      such as clinical expertise as important in moving from evidence to action. In
      contrast, we suggest that EBM should acknowledge multiple dimensions of evidence
      including scientific evidence, theoretic evidence, practical evidence, expert
      evidence, judicial evidence and ethics-based evidence. What EBM loses by not
      acknowledging these dimensions as evidence is the ability, among other things, to
      make and defend judgements based on understandings that complement science and
      are no less important than those science can offer. We argue for a new definition
      of EBM that, without forced accommodation or unacceptable compromise,
      acknowledges dimensions of evidence produced within and outside science.

PMID- 10970003
TI  - Seven characteristics of medical evidence.
AB  - This paper outlines seven essential characteristics of medical evidence and
      describes the implications of these for both the theory of evidence-based
      medicine and clinical practice. The seven characteristics are: (1) Provisional;
      (2) Defeasible; (3) Emergent; (4) Incomplete; (5) Constrained; (6) Collective and
      (7) Asymmetric. It is argued that the epistemological theory that best fits
      medical evidence is that of fallibilism.

PMID- 10970004
TI  - Evidentiary challenges to evidence-based medicine.
AB  - The evidence-based medicine (EBM) movement has exerted a strong influence on
      contemporary medicine. It has been used to define the hierarchy of knowledge in
      clinical medicine by classifying clinical findings according to the perceived
      relevance and validity of the respective methodologies of studies from which
      evidence was collected. In the spectrum of theories of knowledge, EBM
      predominantly relies on findings obtained from population-derived clinical
      research. This reliance on knowledge obtained from population studies sharply
      contrasts with a physiologic model of clinical knowledge advocated by basic
      science researchers and many clinicians. An apparent schism between proponents of
      physiologic and population models in the approach to the practice of medicine has
      been created. This dichotomy between practising physicians and EBM physicians in
      the approach to clinical knowledge should not be irreconcilable. We advocate a
      consilient approach to the interpretation of evidence and the integration of
      medical knowledge. This approach relies on 'linking of facts and fact-based
      theory across various disciplines to create a common groundwork of explanation'.

PMID- 10970005
TI  - Decision analysis in evidence-based decision making.
AB  - Many real world decisions have to be made on a limited evidence base, and
      clinical decisions are at best problematic. We explored some of the reasons why
      decision making in health care is so complex, and examined how decision analytic
      techniques might contribute to problem structuring and to implementation of
      evidence-based practice. We argued that decision analysis could, to some extent,
      overcome complexity of decision making by a clear structuring of the problem and
      a formal analysis of the implications of different decisions. Decision-analytic
      techniques can guide the management of individual patients or can be used to
      address policy questions about the use of treatment for groups of patients.
      However, decision analysis is not without its criticisms, e.g. problems are
      narrowly defined, replacing judgement and dehumanizing care, neglect of process
      utility and lack of primary data to develop decision analytic models. The
      development of evidence-based guidelines is a key component of the UK
      Government's quality strategy led by the National Institute for Clinical
      Excellence (NICE). However, the guidelines approach may lead to conflict when
      assessments of the effectiveness of interventions for individuals (whether or not
      supported by a formal decision analysis) conflict with the recommendations made
      by NICE for cost and clinical effectiveness for aggregate groups of patients.
      Decision analysis may or may not help with this but if guidelines are derived
      from a decision analysis, then the implications of patient preferences should be
      made clearer. However, decision analysis-derived guidelines will make general
      recommendations that may not be appropriate for all individuals. Nonetheless,
      decision analysis does make such implications explicit and propose that the
      guidelines should be supported by some mechanism for determining individual
      patient preferences. It will now need to consider whether some of NICE resources
      should be directed beyond evidence-based guidelines into decision analysis
      derived guidelines and into decision analytical techniques to provide support for
      clinical and cost effective decision making within the patient-clinician
      encounter.

PMID- 10970006
TI  - Evidence-based medicine training in graduate medical education: past, present and
      future.
AB  - Evidence-based medicine (EBM) training remains a challenge to educators,
      particularly in graduate medical education. In this article, I trace the history
      of EBM in American medical education, review traditional journal clubs and
      contrast them to free-standing EBM curricula, petition for the advancement of
      integrated EBM teaching and propose an agenda for future work. Traditional
      journal clubs are unsuitable to teach evidence-based decision making because of
      their exclusive focus on critical appraisal. In contrast, EBM curricula cover the
      identification, appraisal and application of evidence in the context of
      individual patient scenarios. The effectiveness of some recent efforts reflects
      increasing attention to curriculum development principles and scientific rigour.
      The integration of EBM training into residents' established clinical venues
      offers theoretical educational advantages and confronts the challenge of
      practising EBM under the imperatives of 'real time' patient care. Initial
      responses to this formidable challenge show promise, but their feasibility and
      effectiveness remain to be explored. A more complete understanding of the
      epidemiology of residents' emerging clinical questions will inform continued
      curriculum development in integrated EBM training.

PMID- 10970008
TI  - Diaries of evidence-based tutors: beyond 'numbers needed to teach'...
AB  - Interprofessional evidence-based health care courses have been held throughout
      the UK over the last few years, modelled on the approach used in McMaster
      University of using problem-based facilitated small-group formats to achieve the
      stated goals. Both delegates and tutors have been aware of the tensions which are
      inherent within these courses between: (a) the variation in learning cultures
      which is exhibited by the delegates and the effect this has on processes (i.e.
      the tension between the reductionist approach of bioscience and the more
      qualitative leanings of the applied and 'caring' disciplines); and (b) the
      conflict which arises between the goal of 'learning' applied healthcare
      biostatistics and the ability to leave the course with the skills to teach
      others. This qualitative study uses tutor-kept diaries to understand some of the
      tensions apparent to the teaching faculty during a week-long course in Wales, UK.

PMID- 10970007
TI  - Treating individuals according to evidence: why do primary care practitioners do
      what they do?
AB  - Research evidence does not necessarily translate into changed management for
      individual patients, but that may not mean that the evidence has been ignored.
      Drawing on accounts from general practitioners, we use a study of non-rheumatic
      atrial fibrillation (NRAF) to illuminate the processes by which practitioners
      became aware of and assimilated research evidence. We follow that with an account
      of how the evidence was incorporated into practice protocols for anticoagulation
      and then applied to a review of individual patients' records. Practitioners used
      a range of sources of evidence. They reported difficulties arising from their own
      skills and circumstances and from the perceived quality of the evidence. Creating
      a protocol involved overcoming problems of scheduling, resources and managing
      judgements about the value of the review process. In applying the protocol
      practitioners drew on their knowledge of the patients' preferences, circumstances
      and previous specialist consultations. As a result, practitioners made judgements
      that evidence, combined with prior experience, did not support the initiation of
      anticoagulation in 52% of an unselected primary care population with NRAF. Our
      findings have implications for evidence-based practice and for practitioner
      education.

PMID- 10970009
TI  - The role of qualitative research in broadening the 'evidence base' for clinical
      practice.
AB  - This paper presents the case for seeking to broaden the 'evidence base' of
      medicine and health care by the inclusion of qualitative research findings. In
      order for qualitative research to make a significant contribution, advocates of
      this approach must demonstrate its ability to address questions of relevance to
      practice and proponents of EBM must rethink their ideas as to what may constitute
      a research question. A definition of qualitative research is provided,
      highlighting the somewhat different assumptions which underpin this model. The
      potential contribution of qualitative findings is assessed and the paper examines
      the ways in which such insights can be utilized. Finally it addresses the
      question as to how qualitative findings can be incorporated in the 'evidence
      base'.

PMID- 10970010
TI  - In the eye of the beholder: problems of perception in designing a strategy to
      promote evidence-based clinical policy.
AB  - Independent qualitative evaluation of a project designed to ensure that clinical
      policy in specific areas of care in three obstetric units within one English
      health district was based on authoritative evidence. Data from nonparticipant
      observation, interviews, questionnaires and documents were combined to generate a
      description of what the project involved and analyses from the perspectives of
      two key groups of stakeholders: the project proponents and the unit staff whose
      policies the project was intended to address. Key aspects of the project are
      examined from these perspectives to elucidate the assumptions of those involved
      in the project design and assess the adequacy of their attempts to facilitate
      success. Attempts were made to meet many of the accepted criteria for effective
      implementation. Nevertheless, the majority of unit staff retained significant
      doubts about the validity of the project's starting point and the approach
      adopted. The project process was followed as anticipated. After one year the
      intended work programme had been completed. The proponents saw the project as
      quite successful; they were unaware of the extent of the reservations still held
      by unit staff. The proponents focused on potential barriers that 'made sense' in
      the light of their own values and priorities. Failure to recognize the actual
      causes of concern was due to not hearing or listening to unit staff. Intended
      strengths of the project design were viewed quite differently by staff because
      they did not share the proponents' basic premises. Approaches to promoting
      evidence-based practice which take account of the views of all parties regarding
      problems and solutions are more likely to succeed.

PMID- 10970011
TI  - Judging the 'weight of evidence' in systematic reviews: introducing rigour into
      the qualitative overview stage by assessing Signal and Noise.
AB  - The 'weight of evidence' in a topic area can be judged by assessing the 'Signal'
      from available research publications and tempering the importance attached by the
      level of 'Noise' (the inverse of methodological quality). This assessment process
      has validity and reliability and can be applied to the 'qualitative overview'
      stage of systematic reviews. This enables the important themes and areas of
      relevance to the research question to be identified. Important findings from
      individual papers may also be identified providing further information which may
      not be evident from quantitative analysis. The findings from these more
      qualitative stages of analysis complement, but do not replace, quantitative
      analysis.

PMID- 10970012
TI  - A recruitment strategy for cluster randomized trials in secondary care settings.
AB  - Trials of educational or organizational interventions to change clinical practice
      require cluster randomization, that is, randomization of units such as hospitals
      or clinical teams rather than individual patients. Cluster randomization is
      relatively novel in health care settings and raises new methodological
      challenges, in particular: are units willing to be randomized at an
      organizational level; and, what procedures should be followed to successfully
      enrol all of the clinicians in a unit rather than individual clinicians as in
      conventional multicentre trials. This is particularly problematic for trials of
      large units such as hospitals. The aim of this study was to develop and partially
      evaluate a strategy to recruit acute, secondary care NHS hospitals in the UK into
      cluster randomized trials. Literature search and interviews with senior staff in
      acute hospitals and relevant national organizations were used to develop a
      recruitment strategy. The strategy was evaluated by inviting 32 randomly selected
      clinical directorates to participate in a trial feasibility study. A seven step
      recruitment strategy was developed: (1) Identify stakeholders and gatekeepers;
      (2) Inform stakeholders and gatekeepers; (3) Approach gatekeepers; (4) Local
      negotiation; (5) Conduct the research; (6) Feedback to gatekeepers; (7) Feedback
      to stakeholders. Key problems were the possibility of multiple gatekeepers and
      identification of all possible stakeholders in varying organizational structures.
      The strategy was effective in two respects. First, 32 (100%) of the directorates
      approached agreed to participate. Second, baseline data collection was
      successfully achieved in all of the directorates. However, the strategy is costly
      in terms of time and resources. We conclude that NHS trusts are willing to
      participate in cluster randomized trials. This recruitment strategy is successful
      and could be widely adopted, but realistic time and financial cost estimates are
      required at the planning stage.

PMID- 10970013
TI  - Bayesian statistics in medical research: an intuitive alternative to conventional
      data analysis.
AB  - Statistical analysis of both experimental and observational data is central to
      medical research. Unfortunately, the process of conventional statistical analysis
      is poorly understood by many medical scientists. This is due, in part, to the
      counter-intuitive nature of the basic tools of traditional (frequency-based)
      statistical inference. For example, the proper definition of a conventional 95%
      confidence interval is quite confusing. It is based upon the imaginary results of
      a series of hypothetical repetitions of the data generation process and
      subsequent analysis. Not surprisingly, this formal definition is often ignored
      and a 95% confidence interval is widely taken to represent a range of values that
      is associated with a 95% probability of containing the true value of the
      parameter being estimated. Working within the traditional framework of frequency
      based statistics, this interpretation is fundamentally incorrect. It is perfectly
      valid, however, if one works within the framework of Bayesian statistics and
      assumes a 'prior distribution' that is uniform on the scale of the main outcome
      variable. This reflects a limited equivalence between conventional and Bayesian
      statistics that can be used to facilitate a simple Bayesian interpretation based
      on the results of a standard analysis. Such inferences provide direct and
      understandable answers to many important types of question in medical research.
      For example, they can be used to assist decision making based upon studies with
      unavoidably low statistical power, where non-significant results are all too
      often, and wrongly, interpreted as implying 'no effect'. They can also be used to
      overcome the confusion that can result when statistically significant effects are
      too small to be clinically relevant. This paper describes the theoretical basis
      of the Bayesian-based approach and illustrates its application with a practical
      example that investigates the prevalence of major cardiac defects in a cohort of
      children born using the assisted reproduction technique known as ICSI
      (intracytoplasmic sperm injection).

PMID- 10970014
TI  - Individual patient data meta-analysis of randomized anti-epileptic drug
      monotherapy trials.
AB  - Meta-analysis may be based on either aggregate data or individual patient data
      (IPD). Three reasons why IPD are desirable for the meta-analysis of anti
      epileptic drug (AED) monotherapy trials are: (1) to undertake a more complete
      analysis of time-to-event outcomes; (2) to investigate the interaction between
      AED and type of epilepsy; and (3) to undertake re-analysis of the trial to obtain
      results for all relevant outcomes. We demonstrate that IPD meta-analysis is
      possible in AED research. Problems arose from missing data at four levels: (1)
      unknown trials; (2) known trials but no IPD supplied; (3) known trials but
      missing outcome data for some individuals within trials; and (4) known trials but
      missing covariate data for some individuals within trials. Empirical evidence of
      the reliability of meta-analyses based on aggregate rather than individual
      patient data is still lacking. Examples of other benefits such projects may bring
      include improvements to the design of a new trial in the area, in terms of the
      sample size considerations, the definition of outcomes and data collection.

PMID- 10970015
TI  - Why are investigations not recommended by practice guidelines ordered at the
      periodic health examination?
AB  - Evidence-based guidelines recommend few routine investigations for healthy adults
      at the periodic health examination (PHE). However, small studies indicate that
      laboratory tests are commonly ordered at the PHE. This study examined PHE
      laboratory testing that is not recommended by recognized guidelines
      ('discretionary'). Using administrative data from the universal health care
      system in Ontario, Canada, we studied 792,844 adults having a PHE in 1996 and the
      3,727 physicians who administered them. We measured the number of discretionary
      laboratory tests per PHE along with the patient and physician factors potentially
      influencing laboratory testing. A multilevel, multivariate model was used to
      examine the association between the number of discretionary laboratory tests at
      the PHE with patient and physician characteristics. A mean of 7.1 discretionary
      tests (SD 7.1) was ordered per PHE. Renal, haematological, glucose and lipid
      tests each were conducted in more than a third of PHEs. Testing varied
      extensively between physicians and was more common in healthy patients. With the
      exception of age, patient factors had little effect on discretionary testing.
      However, each physician factor we examined was independently associated with the
      number of discretionary tests. Physician specialty, practice volume and previous
      testing patterns had the strongest influence on discretionary testing.
      Discretionary investigations are common at the PHE. Testing varies extensively
      between physicians and seems to be driven more by physician than by patient
      factors. Interventions to modify discretionary test utilization at the PHE should
      consider these physician factors.

PMID- 10970016
TI  - The Leicestershire local guideline adaptation and implementation programme: a
      model for clinical effectiveness?

PMID- 10970017
TI  - Are systematic reviews taking heterogeneity into account? An analysis from the
      Infectious Diseases Module of the Cochrane Library.

PMID- 10970019
TI  - The involvement of neurotrophic factors in the central mechanisms of behavior in
      adult animals.
AB  - In the light of the similarity of the neurochemical mechanisms of behavior during
      ontogenesis and in adult organisms, studies were performed on the effects of
      antibodies to neurotrophic factors--S-100b protein, CSL lectin, and R1 lectin-on
      the acquisition, retention, and reproduction of habituated acoustic startle
      reactions and freezing behavior in adult rats. Antibodies against neurotrophic
      factors were found to have selective, dose-dependent effects on the types of
      behavior investigated. Antibodies to S-100b, CSL, and R1, at a dose of 5 microg,
      induced derangements in the processes of consolidation and/or retention of
      behavioral habits. At a dose of 2 microg, antibodies to S-100b selectively
      blocked the retention of long-term habituation of the startle reaction, while a
      dose of 0.5 microg had no such effect. Antibodies to neurotrophic factors had no
      effect on reproduction of acquired defensive habits.

PMID- 10970020
TI  - Studies of cytokines in nerve tissue cultures.
AB  - The effects of cortexin, epithalamin, and synthetic peptides on the growth of
      processes in sensory neurons and on the development of fragments of cortical and
      subcortical brain structures were studied in organotypic cultures from 10-11-day
      chick embryos. Cortexin (20 and 100 ng/ml), epithalamin (20 and 200 ng/ml),
      polypeptides M and P (2 and 20 ng/ml) had neurite-stimulating actions, evident on
      day 3 of dorsal root ganglion culture. Addition of cortexin (100 ng/ml) or
      polypeptide M (20 ng/ml) to the culture medium of cerebral cortex explants
      stimulated explant development. Addition of cortexin at the same concentration to
      explants of subcortical formations suppressed their development. Epithalamin (200
      ng/ml) or polypeptide M (100 ng/ml) stimulated the development of explants from
      subcortical formations, the existence of the neurite-stimulating effect effects
      of these cytokines provided the basis for identifying the mechanism of action of
      brain peptides.

PMID- 10970018
TI  - The role of volume transmission of adaptogenic signals in forming the adaptive
      reactions of the brain.
AB  - This review presents published data and results from our own studies providing
      evidence for the important role of volume, non-synaptic transmission of
      adaptogenic signals in the mechanisms forming the long-term adaptive reactions of
      the brain. The importance of chemical factors involved in volume transmission and
      secreted by cells in this process is discussed. Special attention is paid to
      peptides-possible mediators of volume transmission of adaptive-type signals.
      Evidence has been obtained for the presence of peptides and their role in the
      mechanism of development of adaptive brain reactions of different origins,
      especially those arising in response to tetanic stimulation of neurons and
      transient hypoxic stress. An original method for testing for the effects of
      neuromodulator factors released by cells in donor slices subjected to these
      treatments on recipient slices was used to show that these factors had pronounced
      effects on synaptic transmission and could induce long-term potentiation of
      synaptic transmission, protecting against functional derangements due to
      prolonged anoxia. Blockade of protein synthesis in donor slices subjected to
      adaptogenic treatments suppressed the appearance of these effects. The review
      concludes with a discussion of the mechanisms of interaction of the synaptic and
      volume transmission of signals involved in forming long-term adaptive brain
      reactions.

PMID- 10970021
TI  - The transient stage of long-term synaptic facilitation in defensive behavior
      command neurons in sensitized snails.
AB  - Experiments on common snails showed that three exposures to sensitizing stimuli
      (10% quinine applied to the snail's head every 15 min) induced synaptic
      facilitation in defensive behavior command neurons LPI1 and RPI1, with
      facilitation of responses to sensory stimuli lasting more than 24 h. Application
      of single stimuli produced transient synaptic facilitation and was expressed in
      responses to tactile stimulation of the head for about 1 h and in responses to
      dilute quinine for 3 h. Serotonin and cAMP imitated stimulus-specific transient
      synaptic facilitation. These substances facilitated the responses of neurons LPI1
      and RPI1 to test stimulation of the head without producing changes in the
      responses to stimulation of other areas of skin on the animal's body. Calmodulin
      antagonists and glutamate NMDA receptor antagonists inhibited sensitization
      induced synaptic facilitation in command neurons. Expression of transient
      synaptic facilitation depended on protein synthesis-it was suppressed by
      anisomycin and cycloheximide. It is suggested that transient synaptic
      facilitation during the acquisition of sensitization is associated with
      activation of translation/transcription processes and subsequent synthesis of
      specific short-lived protein molecules with selectively regulate the synaptic
      "inputs" of command neurons LPI1 and RPI1 from their specific skin innervation
      zones on the snail's head.

PMID- 10970022
TI  - Possible molecular-cellular mechanisms of the regulation of gene expression
      during learning.
AB  - This study is an analysis of the regulatory mechanisms of plasticity. The first
      part provides a short review of the role of DNA-binding transcription factors in
      possible regulatory pathways and their activity in the mechanisms of plasticity.
      Our own data obtained in studies of the molecular mechanisms underlying the
      formation of conditioned defensive reflexes in Helix are then presented. These
      studies show that formation of defensive types of plasticity in Helix is
      accompanied by serotonin-induced translocation of a protein with Rf 0.58 and
      increases in G-protein activity, protein kinase A activity, and expression of the
      c-fos gene. Transcription factors CRE and AP-1 probably have roles in the
      learning process. Gel shift assays demonstrated the existence of transcription
      factors of the CRE and AP-1 families in adult snails. In juvenile snails, which
      were unable to form defensive types of plasticity, the serotonin protein with Rf
      0.58 (the learning "marker") was absent from and was not induced in the CNS. Gel
      shift assay results also showed that transcription factors of the AP-1 family
      were not present and were not induced by serotonin or the protein kinase A
      activator forskolin, though these snails had significant levels of CRE
      transcription factors. Serotonin and forskolin increased the DNA-binding activity
      of CRE in juvenile Helix. The lack of activity of transcription factors of the AP
      1 family in juvenile snails may explain their inability to development
      sensitization and conditioned defensive reflexes.

PMID- 10970023
TI  - Agonistic behavior: a model, experimental studies, and perspectives.
AB  - Agonistic (competitive) behavior includes the manifestations of aggression and
      submissiveness by individuals in conflict situations and is a universal form of
      behavior found in animals of different species. The sensory contact model allows
      aggressive and submissive (inhibited, suppressed) types of behavior to be formed
      in male mice as a result of acquisition of repeated experience of social
      conquests or defeats in daily aggressive interactions. Chronic experience of
      aggression is accompanied by total activation of the dopaminergic systems in the
      victors. At the same time, experience of social defeat leads to changes in the
      state of the serotoninergic and noradrenergic systems of various parts of the
      brains of the defeated animals. As a consequence, significant differences in
      emotional expression, movement activity, investigative activity, communicative
      ability, alcohol consumption, and many physiological aspects were found in
      animals of opposite social groups. The extent and nature of these changes
      depended on the type of social behavior formed by the animals (victors,
      vanquished), the duration of confrontational experience, and the genetically
      determined characteristics of the animals (i.e., which line of mice). The
      possibilities and perspectives of this model of sensory contact in medical
      biological and basic investigations is discussed.

PMID- 10970024
TI  - Identification of Drosophila mutant with memory defects after acquisition of
      conditioned reflex suppression of courtship.
AB  - Four lines were selected from a collection of 33 lines prepared by P insertion
      mutagenesis using a single-copy P-element system; the males of these four lines
      showed memory defects after acquisition of conditioned reflex suppression of
      courting. In two lines (P171 and P95), the dynamics of retention of the
      conditioned reflex in the repeated impregnated-female courting test were similar
      to those of known short-term memory mutants dnc and rut. In line P153, the
      dynamics were more reminiscent of the memory dynamics in a known medium-term
      memory mutant, amn. In line P124, the learning index was insignificant
      immediately after training was completed, which may indicate that this line was
      unable to acquire conditioned reflex suppression of courting. Determination of
      the positions of the P elements (P171: 48A-B; P153: 49B-C; P124: 67B-68A; P95:
      77C-D) showed no correspondence with previously known mutations producing memory
      lesions.

PMID- 10970026
TI  - Expression of the startle reaction in rats genetically predisposed towards
      different types of defensive behavior.
AB  - The magnitudes of startle reactions, consisting of shuddering in response to
      acoustic signals, were studied in rats selected for predisposition to different
      types of defensive behavior-rats with and without passive defensive freezing
      reactions (catalepsy), and Norway rats selected for a lack of defensive
      aggression to humans or for high levels of aggression; studies were performed in
      an SR-Pilot apparatus. These experiments showed that expression of the startle
      reaction to standard sound signal in rats with a genetic predisposition to
      catalepsy was double that in control Wistar rats. A similar but greater
      difference was seen between highly aggressive and non-aggressive rats: the
      amplitude of the startle reaction in rats with high levels of active defensive
      responses was three times that in rats showing no aggression towards humans.
      Extinction of the reflex reaction was significantly slower in highly aggressive
      rats than in non-aggressive rats. A similar tendency was seen in rats with
      genetic predisposition to the passive defensive freezing reaction as compared
      with Wistar rats. It was concluded that animals with an inherited tendency to
      defensive behavior have higher levels of the emotional fear state, regardless of
      the strategy of the defensive behavior.

PMID- 10970025
TI  - Proliferative activity and characteristics of the structural-functional
      organization of the chromosomes in cells of the developing brain, related to the
      genetically determined excitability of the nervous system in rats.
AB  - This report describes the results of a comparative genetic analysis of the
      proliferation activity, level of chromosomal aberrations, and the state of
      interphase chromatin in nerve cells from the developing brains of rat embryos
      from lines with nervous systems of different excitation thresholds. A
      relationship between the basal level of nervous system excitability and these
      cytogenetic characteristics was found. Higher values were seen in embryos of the
      high-threshold line VP1, as compared with the low-threshold line NP1. The role of
      the cytogenetic characteristics of the embryo brain in the processes of CNS
      development and function are discussed in relation to the genetically determined
      level of nervous system excitability.

PMID- 10970027
TI  - Genetic differences in the synthesis and reception of noradrenaline in the mouse
      brain and behavior in a novel environment.
AB  - The activity of tyrosine hydroxylase, the key enzyme in catecholamine
      biosynthesis, was studied along with adrenoceptor density in the brains of male
      CBA/Lac, BALB/cLac, and C57BL/6J mice, which show different responses to novel
      environments. C57BL mice showed the highest level of movement activity and the
      lowest level of emotionality in a novel environment. Mice of this line also
      showed the highest brainstem tyrosine hydroxylase activity. At the same time, the
      density of beta-adrenoceptors in the cortex and hypothalamus of C57BL mice was
      lower than in the other two lines of mice, while the density of alpha2
      adrenoceptors in these parts of the brain was lower than in CBA mice. In BALB
      mice, movement activity was twice as high as in CBA mice, while levels of
      emotionality were similar in these two lines. Tyrosine hydroxylase activity was
      higher in the cerebral cortex of BALB mice, while the density of alpha2
      adrenoceptors was lower than in CBA mice. These results show that increased
      investigative activity and decreased emotionality were seen in animals with
      higher levels of noradrenaline synthesis and decreased density of adrenergic
      receptors in the brain.

PMID- 10970028
TI  - Ethanol modulates the ionic permeability of sodium channels in rat sensory
      neurons.
AB  - The effects of ethanol on tetrodotoxin-sensitive (TTXs) and tetrodotoxin
      resistant (TTXr) sodium channels in rat spinal ganglia were studied using a patch
      clamp method. Application of ethanol (10 and 100 mM) to both sides of membranes
      resulted in decreases in the reversion potentials of both types of sodium
      channels. In the case of TTXr channels, ethanol decreased their selectivity in
      relation to Na ions and altered the sequence of ion selectivity of these channels
      for different cations from row X to row XI of the Eisenman selectivity
      classification. It is suggested that this change in ion selectivity is associated
      with ethanol-induced disruption of hydrogen bonds which stabilize the spatial
      structure of ion channel macromolecules, which may lead to changes in the steric
      parameters of the pores formed by these channels.

PMID- 10970029
TI  - Stimulus-dependent effects in the actions of sodium channel blockers on sensory C
      units.
AB  - Stimulus-dependent inhibition of discharges from cutaneous C fibers from
      mechanothermo-sensitive (MTS) units (nociceptive sensors) can explain the
      paradoxical analgesic effect of local anesthetics at low concentrations,
      insufficient to block axonal conduction of nerve impulses. Three types of
      experiments are proposed which could detect the stimulus-dependent inhibition of
      the terminal section of sensory C units: a method involving repeated series of
      stimuli, the increasing stimulus method, and the spike encounter method. The
      applications of these methods to assessing the magnitudes of the neuroleptic
      effects of local anesthetics and cardiac antiarrhythmics is discussed.

PMID- 10970030
TI  - The effects of the dynamic state of the cytoskeleton on neuronal plasticity.
AB  - The effects of degrading and stabilizing microtubules and microfilaments on the
      formation of plastic reactions were studied in isolated nerve cells from the
      mollusk Lymnaea stagnalis. Degradation of the cytoskeleton affected the
      performance, retention, and repeated acquisition of plastic reactions.
      Stabilization of microtubules led to the appearance of a relationship between the
      dynamics of the development and retention of plastic reactions and the series of
      stimulation. Stabilization of microfilaments led to transient plastic reaction,
      along with long-term reactions. These results show that rearrangements of the
      cytoskeleton have a key role in the processes of neuronal plasticity.

PMID- 10970031
TI  - Involvement of intracellular regulatory systems in the adaptive effects of
      transient anoxia in vitro.
AB  - The involvement of the calcium and phosphoinositide intracellular regulatory
      systems in the molecular-cellular mechanisms of adaptation of the brain to
      hypoxia induced by transient anoxia were studied in slices of rat olfactory
      cortex. Anoxia lasting 2 min initiated the development of moderate but stable
      activation of intracellular regulatory systems during the reoxygenation period,
      with increases in binding of Ca2+ to intracellular hydrophobic domains and
      increases in the level of polyphosphoinositide metabolism. During this period,
      cells in the slices released neuromediator factors into the perfusion fluid;
      transfer of these to recipient slices induced similar changes in the activities
      of intracellular regulatory system components in the recipient slices. After
      anoxia lasting 10 min, NMDA-mediated pathogenic hyperactivity of the calcium and
      phosphoinositide systems developed. Preliminary moderate activation of these
      systems by transient anoxia or neuromodulator factors released by cells in
      response to transient anoxia prevented disruption of intracellular regulatory
      system activity induced by subsequent longer-lasting anoxia.

PMID- 10970033
TI  - Why embodiment now?

PMID- 10970032
TI  - The modulating effects of various muscle factors on the function of motor nerve
      terminals.
AB  - Studies reported here showed that the incubation medium used for frog muscle
      contains factors able to modulate the secretion of mediator from motor nerve
      terminals, with increases in release from low-efficiency synapses and decreases
      in release from high-efficiency synapses. Both the stimulatory and the inhibitory
      effects of the incubation medium are mediated by the corresponding changes in the
      number of available mediator quanta stored. Factors with stimulatory presynaptic
      actions were present mainly in the low-molecular-weight (<10 kDal) fraction of
      the incubation medium. The extent of the stimulatory action of this fraction on
      low-efficiency synapses correlated with the concentration of histidine-containing
      substances.

PMID- 10970034
TI  - Minor impact that qualitative inquiry has on the development of nursing science.

PMID- 10970035
TI  - Dimensions of vulnerability in emergency nurses' narratives.
AB  - Two notions of vulnerability dominate in the nursing literature. In one model,
      vulnerability is equated with susceptibility to particular harmful agents,
      conditions, or events at particular times and is considered something to be
      avoided or resisted. Another view regards vulnerability as the ever-present,
      common condition of all sentient beings and a condition of nurses' access to
      understanding patients' experiences. This article uses data from an ethnographic
      study conducted in two hospital emergency departments to illustrate tensions
      between these two stances toward vulnerability as they are reflected in emergency
      nurses' narratives.

PMID- 10970036
TI  - Experiencing transitions: an emerging middle-range theory.
AB  - Changes in health and illness of individuals create a process of transition, and
      clients in transition tend to be more vulnerable to risks that may in turn affect
      their health. Uncovering these risks may be enhanced by understanding the
      transition process. As a central concept of nursing, transition has been
      analyzed, its components identified, and a framework to articulate and to reflect
      the relationship between these components has been defined. In this article, the
      previous conceptual analysis of transitions is extended and refined by drawing on
      the results of five different research studies that have examined transitions
      using an integrative approach to theory development. The emerging middle-range
      theory of transitions consists of types and patterns of transitions, properties
      of transition experiences, facilitating and inhibiting conditions, process
      indicators, outcome indicators, and nursing therapeutics. The diversity,
      complexity, and multiple dimensionality of transition experiences need to be
      further explored and incorporated in future research and nursing practice related
      to transitions.

PMID- 10970037
TI  - The vulnerabilities of teenage mothers: challenging prevailing assumptions.
AB  - The belief that early childbearing leads to poverty permeates our collective
      understanding. However, recent findings reveal that for many teens, mothering
      makes sense of the limited life options that precede their pregnancies. The
      author challenges several assumptions about teenage mothers and offers an
      alternative to the modern view of the unencumbered self that drives current
      responses to teen childbearing. This alternative perspective entails a situated
      view of the self and a broader notion of parenting and citizenship that supports
      teen mothers and affirms our mutual interdependence.

PMID- 10970038
TI  - Dispelling myths and creating opportunity: a comparison of the strengths of
      single-parent and two-parent families.
AB  - Although single-parent family life has become mainstream in many ways, knowledge
      about these families has been focused predominantly on the chronic problems they
      experience. This study describes the strengths of single-parent families,
      compares these strengths to those of two-parent families, and describes families'
      explanations of the effect of self-identified strengths on health. Although
      single-parent and two-parent families are different structurally, the nature and
      pattern of strengths are found to be more similar than different between these
      two groups. These findings challenge stereotypical views of single-parent
      families that emphasize problems and vulnerability and exclude a consideration of
      their strengths.

PMID- 10970039
TI  - Children exposed to violence: measurement considerations within an ecological
      framework.
AB  - The authors argue that children who are exposed to violence constitute a
      vulnerable and understudied population. Assessment of these children, whether for
      purposes of research or practice, should meet certain criteria that may not be
      satisfied with technology presently available to practitioners and researchers.
      This article presents a number of principles that can improve the precision and
      utility of practitioner and researcher evaluations and assessments, as well as
      the instruments that they develop for these purposes.

PMID- 10970040
TI  - Long-term goals and normalization strategies of children and families affected by
      HIV/AIDS.
AB  - Decreasing morbidity and mortality of HIV/AIDS has created a growing population
      of parents and children who are long-term survivors. Using symbolic interaction
      and ethnographic methods, this study explores families' long-term goals and
      normalization strategies and the relevance of the published attributes of the
      concept of normalization for families affected by HIV disease. Findings indicate
      that treatment complexity and the need for stigma management prevent families
      from defining their lives as normal, but they do deliberately use normalization
      strategies to achieve the following goals: health maintenance for members with
      HIV, facilitation of children's school participation, and enhancement of the
      emotional well-being of all family members.

PMID- 10970041
TI  - Nursing's gender politics: reformulating the footnotes.
AB  - Nursing's survival in the new millennium necessitates the application of a fresh
      lens to the manner in which nurses participate in and perpetuate the insidious
      nature of their oppression. This article critically explores the language and
      activities that annotate nursing's gender politics to expose how language and
      power intersect, facilitating the development of a language of social change.
      Self-deception is found to be a central organizing concept of professional and
      service delivery organizations that perpetuates professional mediocrity, limits
      freedom of thought and action, and preserves the borderline status of nurses.
      Dialogue inclusive of the internal and external systems operating to oppress
      nurses is suggested to transform nurses as collective social agents and reframe
      their sociopolitical reality.

PMID- 10970042
TI  - Effects of 2-deoxy-D-glucose on Acanthocheilonema viteae: rodent filariids as
      studied by multinuclear NMR spectroscopyt.
AB  - A well known glucose antimetabolite, 2-deoxy glucose (2DG) widely used in
      chemotherapy of cancer along with radiation, was evaluated as an antifilarial
      agent by nuclear magnetic resonance. The uptake and metabolism of 2DG in the
      experimental filarial infection Acanthocheilonema viteae was studied by in vivo
      multinuclear NMR. An unusually long retention time of 2DG6P within these
      parasites was observed on continuous 31P NMR monitoring, along with a decrease in
      ATP levels. These results led to therapeutic investigation in A. viteae infected
      host Mastomys coucha. 2DG showed a remarkable adulticidal activity (73.6%) with
      50% sterilization of surviving female worms at a dose of 250 mg/kg x 5, p.o. NMR
      observations and activity profile substantiate the findings of one another,
      directed towards the hitting of bioenergetic machinery of A. viteae by
      macrofilaricidal agent (2DG).

PMID- 10970043
TI  - Physical aging by soft ultrasonic wave enhances ethanol metabolism: metabolic
      process of wine as followed by 400 mhz 1H-NMR spectroscopy.
AB  - In natural aging of spirits or wine, the dynamic structure of ethanol-water
      clusters changes to a smaller and more uniform state. Through experience we know
      that naturally aged ones have higher metabolism than the non-aged ones. Also, the
      same effect as natural aging can be obtained in various types of spirits or wines
      by the treatment for a period of time with soft ultrasonic wave (US). In this
      study, we compared ethanol metabolism in human subjects dosed with non-treated
      white wine (control = CON) and with US treated wine. Ethanol levels in human sera
      were followed by 400 MHz 1H-NMR spectroscopy after administration of wine doses.
      Experimental results indicated that ethanol metabolism was enhanced 18% in
      subjects when US treated wine was used rather than when non-treated (CON) was
      used. Other experiments using rabbits showed that a 20% ethanol-aqueous solution
      was absorbed 18% more rapidly by the group dosed with US wine than by the CON
      group. From these experimental facts, it was theorized that ethanol metabolism
      depends on the rapidity of ethanol absorption in the human body. And it can be
      concluded that US treatment brings about the same effect on spirits or wines as
      natural aging.

PMID- 10970044
TI  - Contents of sulfur amino acids, and cystathionine beta-synthase and gamma-lyase
      activities in various tissues from agkistroden blomhoffi (mamushi).
AB  - The concentrations of sulfur-containing amino acids, taurine, cystathionine,
      methionine and cystine, as well as cystathionine beta-synthase and gamma-lyase
      activities in various tissues of Agkistrodon blomhoffi (mamushi) were measured.
      The concentration of taurine in examined tissues was greater than the
      concentration of other sulfur-containing amino acids. The concentration of
      cystathionine in various tissues was also much higher than those of methionine
      and cystine, but the concentration of cystathionine in the brain was lower than
      that of methionine. In all tissues examined in this study, cystathionine beta
      synthase activity was much higher than that of cystathionine gamma-lyase. The
      ratios of cystathionine beta-synthase to gamma-lyase activities in various
      tissues were 5.6 to approximately 85.6. The concentration of sulfur-containing
      amino acids in muscle and skin divided into eight portions of the body were also
      determined. The concentrations of methionine and cystine in each portion of
      muscle and skin were almost the same, but the concentrations of taurine and
      cystathionine in each portion of the body were varied.

PMID- 10970045
TI  - Identification of a phosphatase activity, toward the phosphopeptide pyroGlu-Asp
      Asp-Ser(p)-Asp-Glu-Glu-Asn, in nuclear extract from HL-60 promyelocitic leukaemia
      cells.
AB  - Total protein extract from HL-60 cells was found to be able to dephosphorylate
      the RNA polymerase II octapeptide pyroGlu-Asp-Asp-Ser-Asp-Glu-Glu-Asn previously
      phosphorylated with protein kinase CKII (pCKII). Fractionation in cytoplasm,
      nuclear and chromatin extracts shows the phosphatase activity to be localized
      only in the nucleus, but not to be bound to the chromatin.

PMID- 10970046
TI  - Antioxidant effect of dipyridamole (DIP) and its derivative RA 25 upon lipid
      peroxidation and hemolysis in red blood cells.
AB  - The antioxidant effects of dipyridamol (DIP), a coronary vasodilator, and its
      derivative RA-25 were compared in intact red blood cells (RBC) and in isolated
      ghost membranes. Both compounds are quite effective antioxidants in cumene
      hydroperoxide-induced lipid peroxidation of RBC, showing a much smaller effect
      for hydrogen peroxide oxidation. The antioxidant effect of DIP was considerably
      higher than that of RA25. For isolated ghost membranes, the apparent IC50 (the
      drug concentration that produces 50% inhibition of lipid peroxidation) in cumene
      hydroperoxide-induced peroxidation was 25 microM, while the maximum protective
      effect of RA-25 was around 30% in the drug concentration range of 50-100 microM.
      The drugs can protect the oxidative hemolysis induced by cumene hydroperoxide
      with a lower effect when the hemolysis is induced by H2O2. The significant
      antioxidant effect against damages induced by cumene hydroperoxide suggests that
      DIP, due to its lipophilic character, can interact with RBC membranes, and the
      protective effect is associated with the binding of the drug to the membrane. On
      the other hand, RA-25 is more hydrophilic than DIP, binds to the membrane to a
      smaller extent, and, for this reason, has a lower antioxidant effect.

PMID- 10970047
TI  - Modified antibiotics-methylated ampicillin and ethylated ampicillin-inhibit
      growth of ampicillin-resistant strain of bacteria.
AB  - Bacterial resistance to antibiotics is a significant problem in health facilities
      and results in higher costs for health care and increased fatalities due to
      infection. The work presented here suggests that antibiotic molecular structure
      can be altered in a selected manner, which will revive the bacterial growth
      inhibiting capability. A bacterial strain PKK3535(DH1), which is resistant to the
      antibiotic ampicillin, was found to be highly growth inhibited by these altered
      forms of ampicillin when tested in tissue culture. The level of growth inhibition
      of bacterial strain PKK3535(DHI) was greater than 50%, for both molecular
      variants of ampicillin that were investigated. The bacteria strain used for
      testing was a clinical isolate obtained from the University Hospital of the
      University of Nebraska, Omaha. These two antibiotic variants were methylated
      ampicillin and ethylated ampicillin. The synthetic procedure for generating these
      variants is presented as well as the molecular structure. The methylated and
      ethylated ampicillin were found to be stable at 0 degrees C for many weeks, were
      somewhat less soluble than normal ampicillin, but dissolved in LB plate media.
      The resistant bacteria strain was plated onto LB media with altered ampicillin
      and profound inhibition of bacteria growth was seen within the first 24 hours of
      incubation. These molecular variants of ampicillin provide evidence of a means to
      combat the proliferation of resistant bacterial strains. The molecular alteration
      of antibiotics may provide a suitable means to study and combat the appearance of
      antibiotic-resistant bacteria.

PMID- 10970048
TI  - Thermophotovoltaic (TPV) properties of hornet cuticle as dependent on relative
      humidity.
AB  - This paper deals with the thermophotovoltaic (TPV) properties of the cuticle of
      the Oriental hornet as assessed over time under different regimens of relative
      humidity (RH). The tests were run at two levels of RH, namely, 30% vs. 90%. Each
      experiment entailed measuring the cuticular voltage and current in the dark as
      compared to under illumination (white light = 700 Lux), and at a temperature
      range of 20-30 degrees C. It was found that increase in the RH level boosts the
      current values by 2-3 orders of magnitude; contrariwise, the voltage values rise
      by about three times with drop in the RH. At high RH, the changes in current
      become rhythmical and each cycle of warming-cooling assumes a distinctly cyclic
      pattern. Under illumination, the current decreases, the polarity reverses and the
      resistance increases. The obtained results are describable by a model of electric
      conductance upon a surface, in this case the hornet cuticle; the findings are
      also discussed and compared with similar phenomena recorded from other substances
      possessing the properties of organic semiconductors.

PMID- 10970049
TI  - Antioxidative enzymes in the liver and kidney of alloxan induced diabetic rats
      and their implications in cadmium toxicity.
AB  - The influence of insulin-dependent diabetes mellitus on the oxidative stress
      caused by cadmium in the liver and kidney of laboratory rats has been studied.
      The results suggest that cadmium and alloxan diabetes independently promote lipid
      peroxidation in both liver and kidney. However, lipid peroxidation diminished in
      the diabetic rats fed cadmium. Administration of cadmium to normal and diabetic
      rats depleted glutathione in liver only. No significant change was observed in
      the activity of glutathione peroxidase in kidney, whereas administration of
      cadmium to diabetic rats stimulated catalase activity when compared to cadmium
      fed rats. The actual mechanism of these effects still remains to be confirmed,
      but an antagonistic relationship between cytotoxic mechanisms of diabetes
      mellitus and cadmium is speculated upon. The insulin-dependent activity of a
      unique form of cytochrome 450j may be involved.

PMID- 10970050
TI  - The effects of J modulation on spin-echo acquisition and calculation of spin-spin
      relaxation time (T2) from the J-suppressed data set.
AB  - The effects of J modulation on localized 1H NMR spectra were observed on
      metabolites with both a short T2 relaxation time like glutamate and a
      comparatively long T2 relaxation time like N-acetyl-L-aspartic acid (NAA). All
      examinations were performed by either the double spin-echo (PRESS) sequence or J
      suppressed PRESS (JPRESS) sequence. Both of the sequences allow spectral editing
      and relaxation time studies of J coupled spins. Water-suppressed proton spectra
      were obtained at 1.5 T (GE Signa) from a 6-8 ml volume of interest. T1 and T2
      relaxation times of some of the major brain metabolites were obtained by varying
      the repetition time and echo time of the JPRESS sequence.

PMID- 10970051
TI  - 'Prodromal Alzheimer's disease': a more useful concept than mild cognitive
      impairment?

PMID- 10970052
TI  - Tau pathology: a marker of neurodegenerative disorders.
AB  - Tau is not only a basic component of neurofibrillary degeneration, but is also an
      aetiological factor, as demonstrated by mutations on the tau gene responsible for
      frontotemporal dementias with parkinsonism linked to chromosome 17. Polymorphisms
      on the tau gene and the hierarchical invasion of neocortical areas by tau
      pathology in numerous sporadic neurodegenerative diseases also suggest that tau
      pathology is a primary pathogenic event in non-familial dementing diseases and a
      lead for solid diagnostic and therapeutic approaches.

PMID- 10970054
TI  - Genetic epidemiology of Alzheimer's disease.
AB  - The genetics of Alzheimer's disease is one of the most complex topics to study
      from an epidemiological point of view, particularly in population-based studies
      on polymorphisms of genes. The present review focuses primarily on some
      conflicting results on genetic epidemiology of Alzheimer's disease, and the major
      difficulties met in such studies.

PMID- 10970053
TI  - Molecular genetics of Alzheimer's disease: the role of beta-amyloid and the
      presenilins.
AB  - Alzheimer's disease is the most common neurodegenerative disorder of aging,
      accounting for an estimated two-thirds of all cases of senile dementia.
      Epidemiologic studies have failed to resolve any single cause of Alzheimer's
      disease and suggest a complex etiology, with environmental and genetic factors
      influencing the pathogenesis. Although the majority of cases are sporadic, a
      small number display familial clustering. Genetic analyses of these pedigrees
      have identified four genes that are involved in the development of Alzheimer's
      disease.

PMID- 10970055
TI  - Contribution of neuroimaging in the diagnosis of Alzheimer's disease and other
      dementias.
AB  - This paper reviews the use of neuroimaging in the diagnosis of dementia,
      especially Alzheimer's disease. Computed tomography is still used to determine
      reversible causes of dementia; however, without clinical symptoms these causes
      are hard to find and computed tomography scanning is only cost-effective in a
      defined group of patients. Using magnetic resonance imaging, atrophy of the
      medial temporal lobe can be assessed volumetrically and visually, with a high
      correlation between the two methods. Medial temporal lobe atrophy is highly
      predictive of Alzheimer's disease, and correlates with neuropsychological
      performance and postmortem histologically measured volume. Cerebral volume
      changes over time seem to differentiate Alzheimer's disease and mild cognitive
      impairment progressing to Alzheimer's disease from controls with high accuracy.
      Studies of the corpus callosum in dementia indicate a cortico-cortical
      disconnection caused by atrophy. Of the new techniques, functional magnetic
      resonance imaging seems the most promising. This technique can possibly play a
      role in predicting Alzheimer's disease in patients with mild cognitive
      impairment. The use of single-photon emission computed tomography and positron
      emission tomography in (early) differential diagnoses seems limited. Lower
      regional cerebral blood flow is related to the severity of dementia and survival.
      Iodine-123 iodobenzamide single-photon emission computed tomography in dementia
      with Lewy bodies seems promising. Current and future positron emission tomography
      studies concentrate on memory function and receptor imaging. The focus in
      neuroimaging, especially magnetic resonance imaging, has shifted to early
      diagnosis and monitoring of the disease course, with a special interest in
      predicting dementia in patients with mild cognitive impairment.

PMID- 10970056
TI  - Recent advances in amyotrophic lateral sclerosis.
AB  - The mechanisms by which mutations of the SOD1 gene cause selective motor neuron
      death remain uncertain, although interest continues to focus on the role of
      peroxynitrite, altered peroxidase activity of mutant SOD1, changes in
      intracellular copper homeostasis, protein aggregation, and changes in the
      function of glutamate transporters leading to excitotoxicity. Neurofilaments and
      peripherin appear to play some part in motor neuron degeneration, and amyotrophic
      lateral sclerosis is occasionally associated with mutations of the neurofilament
      heavy chain gene. Linkage to several chromosomal loci has been established for
      other forms of familial amyotrophic lateral sclerosis, but no new genes have been
      identified. In the clinical field, interest has been shown in the population
      incidence and prevalence of amyotrophic lateral sclerosis and the clinical
      variants that cause diagnostic confusion. Transcranial magnetic stimulation has
      been used to detect upper motor neuron damage and to explore cortical
      excitability in amyotrophic lateral sclerosis, and magnetic resonance imaging
      including proton magnetic resonance spectroscopy and diffusion weighted imaging
      also provide useful information on the upper motor neuron lesion. Aspects of care
      including assisted ventilation, nutrition, and patient autonomy are addressed,
      and underlying these themes is the requirement to measure quality of life with a
      new disease-specific instrument. Progress has been made in developing practice
      parameters. Riluzole remains the only drug to slow disease progression, although
      interventions such as non-invasive ventilation and gastrostomy also extend
      survival.

PMID- 10970057
TI  - Clinical and genetic aspects of spinocerebellar degeneration.
AB  - After decades of confusion as a result of the marked clinical variability of
      spinocerebellar degeneration, molecular analyses have permitted the
      identification of loci and genes, which constitute the basis of a new
      classification. However, even greater genetic heterogeneity is suspected and
      several phenotypes, such as complex forms of spastic paraplegia and autosomal
      recessive ataxias, have not yet been thoroughly explored. Unexpectedly, the genes
      responsible for Friedreich's ataxia and a form of autosomal recessive spastic
      paraplegia place these diseases in the category of mitochondrial disorders. The
      unstable mutations caused by trinucleotide repeat expansions are responsible for
      a growing number of inherited cerebellar ataxias.

PMID- 10970058
TI  - Neural bases of learning and memory: functional neuroimaging evidence.
AB  - Positron emission tomography and functional magnetic resonance imaging studies
      have identified brain regions associated with different forms of memory. Working
      memory has been associated primarily with the bilateral prefrontal and parietal
      regions; semantic memory with the left prefrontal and temporal regions; episodic
      memory encoding with the left prefrontal and medial temporal regions; episodic
      memory retrieval with the right prefrontal, posterior midline and medial temporal
      regions; and skill learning with the motor, parietal, and subcortical regions.
      Recent studies have provided higher specificity, by dissociating the neural
      correlates of different subcomponents of complex memory tasks, and the cognitive
      roles of different subregions of larger brain areas.

PMID- 10970059
TI  - Parkinson's disease and sleep.

PMID- 10970060
TI  - Epidemiology of Parkinson's disease and akinetic syndromes.
AB  - New reports of the incidence, prevalence and mortality of Parkinson's disease and
      parkinsonism are reviewed. Evidence for occupational and lifestyle risk factors
      and protective factors is updated. Recent genetic epidemiology studies of
      parkinsonism in twins and families, and studies that investigated imaging and
      physiologic markers of dopaminergic function in members without parkinsonism are
      presented.

PMID- 10970061
TI  - Prevention and therapeutic strategies for levodopa-induced dyskinesias in
      Parkinson's disease.
AB  - Levodopa-induced dyskinesias represent a major shortcoming of Parkinson's disease
      management, and its pharmacological treatment is generally unsatisfactory.
      However, the conclusive demonstration of the benefits associated with early
      prescription of a dopamine agonist, the antidyskinetic properties of 'old'
      antiparkinsonian compounds such as amantadine, and the striking results of
      functional stereotatic neurosurgery are extremely important advances for the
      treatment of levodopa-induced dyskinesias.

PMID- 10970062
TI  - Tremor.
AB  - Tremor research during the past year has focused on clinical differential
      diagnosis, and a new clinical classification has been developed. The origin of
      tremor is thought to depend on unstable central loops, and new coherence data
      suggest that these often involve the motor cortex. Gabapentine has been assessed
      for efficacy in some tremors, and deep brain stimulation of the ventrolateral
      thalamus has been shown to be safer and more effective for severe essential and
      parkinsonian tremor than thalamotomy.

PMID- 10970063
TI  - Recent advances in Huntington's disease.
AB  - Huntington's disease is a progressive and fatal neurological disorder caused by
      the expansion of a CAG trinucleotide repeat in exon 1 of the gene coding for a
      protein of unknown function that has been named huntingtin. The exact cause of
      neuronal death in Huntington's disease is unknown; however, the leading
      hypothesis is that of excitotoxicity and apoptosis induced by a defect in energy
      metabolism that may be caused by oxidative stress. How mutant huntingtin might
      cause these processes is unknown. New animal and cell models provide insights
      into the mechanism of pathogenesis and the search for the development of
      effective therapies.

PMID- 10970064
TI  - Recent advances in degenerative ataxias.
AB  - Since the discovery of the first mutations that cause hereditary ataxias in the
      early 1990s, there has been continuous progress in deciphering the molecular
      pathogenesis of degenerative ataxias. Recent research in Friedreich's ataxia, the
      most frequent recessive ataxia, has provided further evidence that the clinical
      phenotype of this disorder is caused by abnormal oxidative phosphorylation due to
      mitochondrial dysfunction. The dominantly inherited spinocerebellar ataxias
      (SCAs) are genetically heterogeneous. Up to now, 11 distinct loci have been
      identified. The mutations that cause SCA1, SCA2, SCA3, SCA6 and SCA7 share the
      common feature of an expanded CAG sequence, encoding an abnormally long
      polyglutamine tract within the respective gene products. Recent pathogenetic
      research points to the importance of abnormal protein-protein interaction and
      altered gene transcription. The aetiology of many sporadic ataxias remains
      obscure. In some patients, association of ataxia with specific serum antibodies
      (antigliadin, antiglutamic acid decarboxylase) suggests an immune pathogenesis.

PMID- 10970065
TI  - Paroxysmal dyskinesias as a paradigm of paroxysmal movement disorders.
AB  - Paroxysmal dyskinesias are genetically and clinically heterogeneous. Paroxysmal
      kinesigenic choreoathetosis is frequently familial, with autosomal-dominant
      transmission. Benign infantile convulsions can be observed in these families and
      both diseases as linked to the pericentromeric region of chromosome 16. Two
      different forms of paroxysmal dystonic choreoathetosis are distinguished on
      clinical grounds, by the presence or absence of spasticity, and genetically, as
      they are linked with loci on different chromosomes. Among the paroxysmal
      disorders, these diseases may belong to the group of channelopathies.

PMID- 10970067
TI  - Bibliography. Current world literature. Movement disorders.

PMID- 10970066
TI  - Bibliography. Current world literature. Degenerative diseases.

PMID- 10970068
TI  - A simple histochemical assay to detect cancer cells.
AB  - Oxygen insensitivity of cancer cells and oxygen sensitivity of non-cancer cells
      in the histochemical assay of glucose-6-phosphate dehydrogenase (G6PD) activity
      enables detection of cancer cells in unfixed cell smears or cryostat sections of
      biopsies. The assay is based on reduction of the tetrazolium salt neotetrazolium.
      It is a cheap assay that is easy to perform. It takes only 30 min at the most.
      The test discriminates between adenomas and carcinomas of colon and rectum with a
      certainty higher than 80% and is the best prognosticator of survival of
      colorectal cancer patients. Pancreatic cancer can be discriminated from
      pancreatitis with 100% certainty. Therefore, the assay is an excellent tool for
      the pathologist to provide additional information in difficult cases of diagnosis
      of cancer and for prognosis.

PMID- 10970069
TI  - Development of the innervation of long bones: expression of the growth-associated
      protein 43.
AB  - It has been known from clinical and experimental observations that the peripheral
      nervous system is involved in the development of long bones. Expression of growth
      associated protein 43 (GAP-43/B-50) was found in axonal growth cones during
      embryonic and postnatal ontogeny as well as in regenerating axons after nerve
      injury. The aim of the present study was to examine the occurrence of growing
      nerve fibers in rat tibia from gestational day 16 (GD 16) to postnatal day 28
      (PD28). An indirect immunoenzymatic reaction using antibodies raised against GAP
      43 was applied to detect outgrowing nerve fibers penetrating into the developing
      bone. On GD 16 and GD 17 no GAP-43-immunoreactive (IR) fibers were observed in
      the close vicinity of bone rudiments. On GD19 GAP-43-IR fibers were scarcely
      present within the periosteum of the central portion of the diaphysis. In the
      perichondrium surrounding the proximal epiphysis, nerve fibers were first
      detected around birth. From PD1 onward, numerous fibers were seen in the fibrous
      buds of the perichondrium at the epi-metaphyseal junction (Ranvier's grooves),
      some of them being adjacent to the blood vessels. Nerve fibers penetrating into
      the bone and located in the bone marrow, predominantly associated with blood
      vessels, were first observed on GD21 and their number increased with further
      development. They were initially located in the central portion of the diaphysis
      and later extended towards the metaphyses. On PD4 an increased number of GAP-43
      IR fibers appeared in the perichondrium of proximal and distal epiphyses. In the
      fibrous strands penetrating into the epiphyses and in the secondary ossification
      centers, nerve fibers were first observed on PD10. From PD14 onward the pattern
      of tibial innervation remained unchanged but the intensity of GAP-43
      immunostaining visibly decreased. The present study demonstrates that developing
      long bones of rat hindlimbs are supplied by growing nerve fibers immunoreactive
      for GAP-43 from GD 19 onward. Time and location of their appearance were at least
      partially correlated with known events taking place during long bone development,
      e.g. formation of primary and secondary ossification centers. Decreased
      expression of GAP-43 immunoreactivity in later developmental stages is believed
      to reflect nerve fiber maturation.

PMID- 10970070
TI  - Immunohistochemical localization of estrogen receptors in the ovine corpus luteum
      throughout the estrous cycle.
AB  - Using immunohistochemistry and Western blot analysis we attempted to identify the
      estrogen receptors in ovine luteal cells at different stages of the estrous
      cycle. Monoclonal antibody against estrogen receptors was used for
      immunolocalization of estrogen receptor-alpha in corpora lutea sections.
      Generally, the most intense cytoplasm staining was present in large luteal cells.
      On the 6th day of the estrous cycle, weak immunostaining of estrogen receptors
      was observed in large luteal cells as well as in the connective tissue. Luteal
      cells from regressing corpora lutea expressed the weakest immunostaining. The
      most intense immunoreactivity for estrogen receptors was found in sections of
      corpora lutea collected on the 9th day of the cycle. Both, cytoplasmic and
      nuclear localization was observed depending on cell types in the ovine corpus
      luteum. Our studies demonstrated the presence of the estrogen receptor-alpha in
      the luteal cells and suggested an autocrine/paracrine role of estrogen in the
      regulation of estrous cycle in sheep.

PMID- 10970071
TI  - Effect of vasoactive intestinal polypeptide (VIP) on growth hormone (GH) and
      prolactin (PRL) release and cell morphology in human pituitary adenoma cell
      cultures.
AB  - Six GH adenomas and three prolactinomas were investigated by light- and electron
      microscopic morphological and immunocytochemical methods and the effect of
      vasoactive intestinal polypeptide (VIP) on growth hormone (GH) and prolactin
      (PRL) secretion was tested in vitro. The tumour cells of the acromegalic patients
      revealed both GH and PRL immunoreactivity while prolactinomas showed only PRL
      activity. All the adenomas stained immunocytochemically also for VIP. By electron
      microscopy, the tumours included two densely and two sparsely granulated GH, two
      mixed GH/PRL, and three sparsely granulated PRL adenomas. The dissociated cells
      were explanted, and cultured in vitro. The cultures in micro test plates were
      treated with VIP at different concentrations between 10(-5)-10(-12) M. GH and PRL
      contents in the culture media were measured by radioimmunoassay. GH release was
      significantly stimulated by VIP in a dose-dependent manner over the whole
      concentration range, while VIP was effective on the PRL release only at 10(-6)
      10(-7) M concentration. The cells of a mixed adenoma were grown in Petri dishes
      and used for ultrastructural and immunocytochemical studies. The cytoplasmic
      structure of the cells treated with VIP corresponded to that of active hormone
      secreting cells with large ergastoplasmic fields and Golgi zones containing
      secretory granules. Massive exocytotic events were encountered mainly in the GH
      type cells. GH and PRL double immunocytochemistry showed the predominance of GH
      cells, many of them containing low amounts of PRL as well. Cells predominantly
      containing PRL were spread among them, they also might contain GH as well. Some
      of the cells contained only a single immunoreactive hormone. The intensity of
      gold labelling of the secretory granules appeared higher in the VIP-treated cells
      than in the untreated control ones which showed a cytoplasmic structure
      characteristic of glandular cells with low secretory activity. As all the adenoma
      cells both contained and reacted to VIP, our results are in agreement with an
      autocrine or paracrine effect of this peptide. The fine structure of the cells in
      the cultures treated with VIP supply an additional argument to the assumption
      that VIP may serve as a growth factor for these cell types.

PMID- 10970072
TI  - Encapsulation of parathyroid cells in hollow fibers: a preliminary report.
AB  - The purpose of experiments was to evaluate the survival and functioning of human
      parathyroid cells after encapsulation in hollow fibers (HFs). The polypropylene
      HFs K600(PP Accurel (Akzo-Nobel, Germany) of inner diameter 0.6 mm, wall
      thickness 0.2 mm, original or surface modified were used for encapsulation.
      Production of parathormone (PTH) by encapsulated cells was measured in vitro. HF
      were filled with parathyroid cell suspension and tightly closed. Encapsulated
      cells were cultured for 9 or 33 days in RPMI 1640 containing 10% FCS or in
      Chang's medium. The level of PTH, produced by encapsulated cells was evaluated in
      the culture medium with radioimmunoassay test (RIA). The assays were performed
      every 2-4 days. The result of PTH assay was similar in both types of tested media
      as well as with unmodified and modified HFs, being 2-4 pg/ml of culture medium
      per 10(3) encapsulated cells. In conclusion, encapsulation in original or
      modified HFs ensures diffusion of nutrients from culture medium to encapsulated
      cells and allows for functioning of cells for at least 33 days in vitro.

PMID- 10970073
TI  - Evaluation of biocompatibility of apatite-wollastonite ceramics in fibroblast
      cultures.
AB  - The aim of this work has been to test the biocompatibility of four bioactive, gel
      derived glass-ceramic materials of CaO-PO2-SiO2 system, modified by addition of
      boron, aluminum and magnesium compounds. We have examined the growth, collagen
      synthesis, adhesion and morphology of NRK rat fibroblasts cultured in direct and
      indirect contact with biomaterials. The growth of cells cultures has been
      quantified by two methods: [3H]thymidine incorporation and direct counting of
      cells. The level of collagen synthesis has been used as a parameter describing
      metabolic activity of cells. Cellular morphology has been assessed following 24 h
      and 4 days of culturing cells on biomaterials by using SEM and confocal
      microscopy, respectively. Additionally, in order to obtain information about the
      attachment of cells to substratum the presence of focal contacts has been
      examined. The results of all the experiments have demonstrated that none of the
      materials under study significantly altered cellular functions that were tested.
      This indicates that additions of MgO, Al2O3 and B2O3 have not induced
      cytotoxicity of the materials under study. This qualifies them for further in
      vivo experiments.

PMID- 10970075
TI  - International Research Group on Reconstructive Preprosthetic Surgery. Consensus
      report.

PMID- 10970074
TI  - Localization of selenium deposits in meristematic cells of Allium sativum L.
      roots treated with selenium salts.
AB  - Ultrastructural analysis of garlic roots treated for 24 h with sodium selenate or
      sodium selenite at the concentrations 80, 160, 320 microM revealed the presence
      of selenium deposits in meristematic cells. They appeared as small and large
      granules or aggregates of electron-dense material. Many small granules were
      localised in plastids but some in mitochondria, endoplasmic reticulum as well as
      in Golgi apparatus, nucleus and cytoplasm. Sometimes the large granules were seen
      in cytoplasm but aggregates of electron-dense material only in vacuoles. It seems
      possible that these deposits represent a non-dissolved form of selenium, i.e.
      elemental selenium or its complexes with other ions.

PMID- 10970076
TI  - Salivary glands as a model for craniofacial applications of gene transfer.
AB  - The potential applications of gene transfer technology to all branches of
      medicine are increasing. It is quite likely that within the next 10-20 years
      surgical practice routinely will utilize gene transfer, at least adjunctively.
      The purpose of this review is to familiarize the oral and maxillofacial surgeon
      with this technology. Studies performed with salivary glands in animal models are
      presented as examples of proof of concept.

PMID- 10970077
TI  - Extended genioplasty: long-term cephalometric, morphometric and sensory results.
AB  - The incision, dissection, osteotomy design and fixation are important technical
      considerations when performing a genioplasty. The purpose of this study was to
      describe an extended genioplasty technique and to evaluate stability of position,
      form, surface area of the chin and incidence of postoperative sensory deficit.
      Records of 15 consecutive adult patients who underwent the extended genioplasty
      procedure were reviewed. The technique included incision in the labial vestibule
      from 2nd premolar to 2nd premolar, dissection, mobilization and retraction of the
      mental nerves, osteotomy parallel to the occlusal plane extending proximally to
      the antegonial notch and rigid fixation. Lateral cephalograms pre- and
      postoperatively and at the latest follow-up (> 6 months) were analyzed by linear
      and computer morphometric measurements to evaluate changes in position, shape and
      surface area of the chin. Neurosensory data from examination or questionnaire
      were recorded. Immediately postoperatively (T1), mean advancement in the sagittal
      plane was +8.7 mm and increase in surface area was +1.1 cm2. At the end of follow
      up (T2), there were no significant changes (T2-T1) in chin position or surface
      area. Inferior border form was rated as smooth in all cases. Neurosensory
      evaluation revealed that 12/12 patients evaluated had functional sensory return
      at T2.

PMID- 10970078
TI  - Effect of temporomandibular joint arthrocentesis on synovial fluid mediator level
      of tumor necrosis factor-alpha: implications for treatment outcome.
AB  - Temporomandibular joint (TMJ) pain is a predominant sign and symptom in patients
      with temporomandibular disorder, and a common cause of chronic orofacial pain.
      Arthrocentesis of the upper joint space proved to be effective in reducing TMJ
      related pain and reestablishing normal mandibular range of movement in patients
      diagnosed for a 'closed lock'. Using the therapeutic approach of arthrocentesis
      in TMJ-related instances of capsulitis/ synovitis (C/S) with a recency of first
      pain onset of < or =6 months, the purpose of the present study was to evaluate
      whether the TMJ-related variable synovial fluid (SF) level of TNF-alpha may be
      linked to the cessation of related signs and symptoms associated with the
      performance of arthrocentesis and hydraulic distension. In 23 patients with a
      specific temporomandibular disorder diagnosis of unilateral C/S with a recency of
      first pain onset of < or =6 months, TMJ SF aspirates were obtained from the pain
      and contralateral non-pain sides immediately before and after arthrocentesis.
      Visual analog scales were used for pre- and postoperative self-assessment of TMJ
      related pain during function, while enzyme-linked immunosorbent assays were
      applied for measurement of the tumor necrosis factor-alpha (TNF-alpha)
      concentration. With a mean SF TNF-alpha level of 13.91 ng/ml associated with the
      pain side, and a mean SF TNF-alpha level of 7.73 ng/ml associated with the non
      pain side, a statistically significant difference was found between the sample
      groups (P=0.001). Arthrocentesis led to a significant intraoperative decrease of
      the respective preoperative SF TNF-alpha levels, namely 61.64% (P=0.000) on the
      pain side and 89.50% (P=0.000) on the non-pain side, while reduction of TMJ
      related pain during function was 73.17%, (P=0.000). Clinical evaluation showed a
      significant reduction in the prevalence of TMJ-related diagnoses of C/S
      (P<0.001). There was no change in the prevalence of associated TMJ-related
      diagnoses of internal derangement. In view of the fact that the described
      technique of TMJ SF analysis may be suggested as a valuable diagnostic method for
      the detection of biochemical SF events, the results of this study should
      encourage research in its potential uses so that it can become established as a
      reliable diagnostic approach. Further, the findings may support the concept of
      bilateral arthrocentesis to be effective in the treatment of patients with a
      unilateral specific TMD diagnosis of non-chronic C/S.

PMID- 10970079
TI  - Effects of orthognathic surgery on temporomandibular joint dysfunction. A
      controlled prospective 4-year follow-up study.
AB  - A prospective follow-up study was performed to examine the influence of
      contemporary orthognathic treatment on signs and symptoms of TMJ dysfunction.
      Sixty consecutive patients were examined once preoperatively and twice
      postoperatively, and Helkimo's Anamnestic and Dysfunction Indices (Ai and Di)
      were determined. The prevalence of headache was also assessed. The average follow
      up was 4 years from the initial examination. A group of 20 patients with a
      similar type and grade of dentofacial deformity, who did not wish to have surgery
      or other occlusal therapy, served as a control group. The majority (73.3%) of the
      patients had signs and symptoms of TMJ dysfunction (TMD) in the initial phase. At
      final examination the prevalence of TMD had been reduced to 60% (P=0.013). There
      was a dramatic improvement in headache: initially 38 (63%) patients reported that
      they suffered from headache, but at the final visit only 15 (25%) did so. It is
      concluded that functional status can be significantly improved and pain levels
      reduced with orthognathic treatment. The risk for new TMD is extremely low. No
      association, however, could be shown between TMD and the specific type or
      magnitude of dentofacial deformity.

PMID- 10970080
TI  - Rehabilitation of patients with severe (Class VI) maxillary resorption using Le
      Fort I osteotomy, interposed bone grafts and endosteal implants: 1-8 years follow
      up on a two-stage procedure.
AB  - The 1 to 8 years follow-up results on a group of 15 patients who underwent a Le
      Fort I osteotomy with interposed bone grafts and who received implants at a
      second stage, are reported. The procedure proved to be extremely reliable in that
      sufficient bone was present for maximum size implants, whilst implant survival
      appeared to be high (94.6%). The forward advancement was stable and no
      discernible relapse occurred after prosthesis placement. All patients but one
      were highly satisfied with the aesthetic result and the rehabilitation of
      function.

PMID- 10970081
TI  - Repair of the radial free flap donor site with full or partial thickness skin
      grafts. A prospective randomised controlled trial.
AB  - The radial forearm free flap has become the mainstay in the reconstruction of
      soft tissue defects following ablative resection in the oral cavity. The method
      of repair of the associated forearm tissue defect has been the subject of
      considerable debate. The options range from direct closure, to local soft tissue
      flaps or skin graft repair. Larger defects usually require a skin graft and we
      have routinely used partial thickness skin. An audit of our complication rate led
      to the consideration of whether a full thickness repair would reduce the
      morbidity. We randomly allocated successive patients to receive full or partial
      thickness skin graft repair of the radial donor site in a consecutive series of
      68 patients over an 18-month period. Sixty-four patients completed the initial
      assessment period of wound healing. Thirty seven patients completed a
      questionnaire at one year to subjectively assess the aesthetic appearance of the
      forearm wound and the skin graft donor site. They were also assessed for pain at
      both sites. The partial thickness donor site required significantly more re
      dressings. There was no significant difference between the two groups in graft
      take or number of re-dressings at the recipient site. There was no significant
      difference in patient assessment of aesthetic appearance or pain in either the
      forearm recipient site or the skin graft donor site. Provided that an adequate
      graft is taken, full thickness and partial thickness skin grafts have the same
      short-term and long-term outcomes in the repair of the radial free flap donor
      site.

PMID- 10970082
TI  - Negative pressure wound dressing of the radial forearm donor site.
AB  - Donor site complications of the radial forearm are a significant cause of post
      operative morbidity. 15 patients had radial forearm free tissue donor sites
      treated with split skin grafts and a negative pressure dressing. All grafts
      showed 100% take at 5 days. The advantages of this technique include rapid
      healing at an unfavourable graft recipient site, increased graft take and
      decreased donor site complications. This method is ideally suited for the
      management of large defects. The dressing can be quickly and easily applied and
      there have been no significant complications.

PMID- 10970083
TI  - Free omental transfer for osteoradionecrosis of the mandible.
AB  - Osteoradionecrosis (ORN) of the mandible can arise following therapeutic
      radiotherapy for head and neck cancer. The incidence is quoted as 10-15%.
      Conservative and surgical therapies used for ORN have included vascularized
      osteocutaneous flap transfers, hyperbaric oxygen and ultrasound therapy. We have
      used an omental transfer for ORN without a segmental resection. We wrapped the
      affected mandible within the omentum in order to promote revascularization and
      neocellularity. Four patients suffering from ORN have undergone omental
      transfers. Two cases developed pathologic fractures postoperatively that were
      successfully treated by conservative management. In all cases, the patients'
      intractable pain improved, and no patient showed recurrence of ORN or wound
      dehiscence. Postoperative bone scintigrams showed the same degree of accumulation
      in the lesion as in normal adjacent bone. These results demonstrate the
      effectiveness of omental transfer and suggest that omental transfer has a
      promising place in the management of ORN.

PMID- 10970084
TI  - Pirogoff's Triangle revisited: an alternative site for microvascular anastomosis
      to the lingual artery. A technical note.
AB  - This technical note aims to draw the surgeon's attention to the lingual artery in
      its course through Pirogoff's Triangle when looking for an appropriate recipient
      artery in the neck. Nowadays, free vascularised tissue transfer is used routinely
      in the reconstruction of defects in the maxillofacial area. Comfortable access to
      a healthy recipient artery is a major factor in ensuring a successful result.
      Traditionally, Pirogoff's Triangle is the ideal site to expose the lingual artery
      for ligation in case of severe haemorrhage of the tongue. This study shows that
      the lingual artery at this site is also well suited to perform a microvascular
      anastomosis, as the Triangle offers a convenient access, which is relatively
      horizontal and not hampered by the mandibular border. The artery is of good
      calibre and seems fairly resistant against arteriosclerosis.

PMID- 10970085
TI  - Aetiology of nasopharyngeal glioma.
AB  - A case of nasopharyngeal glioma is presented in which the postnatal scans clearly
      show intracranial communication, whilst subsequent scans and surgical exploration
      could not demonstrate this finding. This case seems to confirm that the aetiology
      of these lesions is due to an encephalocele that subsequently loses its
      connection with the brain.

PMID- 10970086
TI  - Simple cryosurgical treatment for oral lesions.
AB  - This article describes a simple and effective cryosurgical treatment for 92
      patients who had 102 benign oral lesions. The procedure was performed by direct
      application of liquid nitrogen to the lesion using a cotton swab on an outpatient
      basis. This treatment required no sophisticated equipment and gave very
      satisfactory results. There was no intra- or postoperative bleeding, no surgical
      defects, minimal scarring, and no infection following treatment. The results
      demonstrate that this is an atraumatic form of therapy in comparison to
      conventional surgery.

PMID- 10970087
TI  - Percutaneous dilatational tracheostomy: haemorrhagic complications and the
      vascular anatomy of the anterior neck. A review based on 497 cases.
AB  - In a series of 497 PDT procedures done in the intensive therapy unit at Morriston
      Hospital between 1992 and 1999, PDT was abandoned because of bleeding in 6
      patients and was noted to be a problem in a further 18 cases (overall incidence
      4.8%). In all cases, haemorrhage was successfully arrested. Surgical tracheostomy
      was necessary in 6 of these 24 cases. The source of bleeding in 4 of these
      patients was attributed to the inferior thyroid vein (2 cases), high
      brachiocephalic vein, and possibly an aberrant anterior jugular communicating
      vein, respectively. In one patient, the vessel presumed injured could not be
      identified and in another patient, bleeding was related to multi-system disease.
      We conclude that the risk of bleeding, although low, can be minimised if the
      operator maintains a high index of suspicion for aberrant vascular anatomy and
      investigates possible abnormalities with diagnostic ultrasound. Injury to vessels
      low in the neck can be reduced by not fully extending the neck and siting the
      stoma at the upper tracheal rings. The possibility of developing a
      tracheoarterial fistula is reduced if the stoma is situated above the 4th
      tracheal ring and fibreoptic endoscopy is used to confirm correct tracheostomy
      tube placement.

PMID- 10970088
TI  - Alterations of adenomatous polyposis Coli (APC) gene in oral squamous cell
      carcinoma.
AB  - The present study assessed the roles of Adenomatous Polyposis Coli (APC) tumor
      suppressor gene during oral carcinogenesis. Reduction of APC transcript levels
      and APC loss of heterozygosity (LOH) were found in 39% (7/18) and 29% (10/34)
      cases of oral squamous cell carcinoma (OSCC), respectively. The apparent APC
      heterozygosity (27%) in non-cancerous matched oral tissue (NCMOT) adjacent to
      OSCC at an exon 11 locus was significantly lower than normally found in the
      Taiwanese population (49%). These findings suggest that the allelic status of APC
      could indicate a cancer risk. No polymorphism of 11307 allele of APC was
      identified in NCMOT or OSCC. Our data indicated that alterations of APC are
      frequent molecular changes of OSCC. Advances in understanding of the APC
      alterations that accompany OSCC development might provide a means for early
      diagnosis and possibly new therapeutic strategies.

PMID- 10970089
TI  - Survey of Australian and New Zealand Oral and Maxillofacial Surgery trainees and
      recent specialists--workforce issues.
AB  - This study examined Oral and Maxillofacial Surgeon (OMS) workforce issues in
      relation to current training in Australia and New Zealand. Earlier findings
      identified that there was a requirement of approximately 6 additional OMS
      specialists per year in Australia and one per year in New Zealand to maintain an
      adequate level of supply in the profession. It was found in this study that
      through to the early part of the next decade the number of OMS entering the
      Australian workforce is appropriate (5.9 per annum), but there would appear to be
      concerns about the sufficiency of the number entering the New Zealand workforce
      (0.7 per annum). In addition, the study also found possible maldistribution in
      the location of intended future practices, with possible shortages outside of the
      metropolitan areas.

PMID- 10970090
TI  - What to do with HLA-DO?
AB  - Antigenic peptide binding to MHC class II molecules in the endocytic pathway
      occurs via a multifactorial process that requires the support of a specialized
      lysosomal chaperone called HLA-DM. DM shows both in primary amino acid sequence
      and quaternary structure a high homology to both MHC class I and class II
      molecules. Like the peptide presenting class II molecules, DM is expressed in all
      professional antigen presenting cells. DM catalyzes the dissociation of peptides
      that do not bind stably to the class II peptide-binding groove, thereby leading
      to the preferential presentation of stably binding antigenic peptides. The
      recently discovered HLA-DO molecule is mainly expressed in B cells and associates
      with DM, thereby markedly affecting DM function. Like DM, the genes encoding the
      HLA-DO heterodimer lie within the MHC class II region and exhibit strong homology
      to classical class II molecules. This review evaluates the unique effects of DO
      on DM-mediated antigen presentation by MHC class II molecules and discusses the
      possible physiological relevance for the B cell-specific expression of DO and its
      function.

PMID- 10970091
TI  - Tbt-1, a new T-box transcription factor induced in activated Th1 and CD8+ T
      cells.
AB  - Differentiation of CD4+ T cells into T helper (Th) 1 or Th2 cells requires the
      cytokines interleukin (IL)-12 and IL-4, respectively. However, transcription
      factors that regulate expression of Th1 or Th2 cell-specific genes remain largely
      unclear. In the present study, a new Th1-specific transcription factor, named Tbt
      1 (T-box protein expressed in T lymphocytes), was identified. Tbt-1 is a novel
      member of the T-box family, which is characterized by a conserved T-box DNA
      binding domain. Unlike other known T-box proteins that regulate embryo
      development and organogenesis, Tbt-1 expression is restricted to adult lymphoid
      organs. Tbt-1 mRNA is only detected in peripheral lymphoid tissues such as
      spleen, lymph nodes, and blood leukocytes, but not in thymus or bone marrow. Tbt
      1 mRNA is not detected in resting T cells but is strongly induced in
      differentiating Thl cells and CD8+ cytotoxic effector cells. In contrast, Tbt-1
      expression was not observed in the entire process of Th2 cell differentiation. In
      addition, phylogenetic analyses indicate that Tbt-1 co-evolved with adaptive
      immune responses. Thus, Tbt-1 is the first T-box transcription factor shown to be
      specific for Th1 cell differentiation.

PMID- 10970092
TI  - Molecular cloning of the C6A form cDNA of the mouse sixth complement component:
      functional integrity despite the absence of factor I modules.
AB  - The sixth complement component (C6) is an essential component of the biologically
      active C5b-9 membrane attack complex of the complement system. The multimolecular
      C5b-9 complex is an important mediator of the biological effects of the activated
      complement system through its prominent cell signaling and cytolytic functions.
      To begin to provide essential information and reagents needed to analyze the
      functions of the complement system in mouse models of human diseases, the cDNA of
      the A form of mouse C6, which is present in all mouse strains, was cloned and
      characterized structurally and functionally. Although strikingly homologous in
      deduced amino acid sequence and modular structure to human C6 (75% identity),
      mouse C6 is substantially smaller due to the absence of the two carboxyl-terminal
      factor I modules (FIMs) found in human C6. Various approaches, including studies
      with antibody generated to recombinant mouse C6, failed to reveal evidence for
      FIMs in this form of mouse C6. Despite the absence of these modules in C6A,
      reported to be important for interactions with C5 in the human system, mouse C6A
      is functionally active and is readily incorporated into the mouse C5b-9 complex.

PMID- 10970093
TI  - Gene structure of the mouse leukocyte cell surface molecule Ly9.
AB  - The Ly9 glycoprotein is a member of the immunoglobulin (Ig) superfamily, which is
      expressed on the cell surface of B and T lymphocytes. With two alleles (Ly9.1 and
      Ly9.2), it was first described as an alloantigenic marker of lymphocyte
      differentiation. Ly9 consists of four Ig-like domains with the structural
      features of the CD2 subfamily, which includes CD2, CD48, CD58, 2B4, CD84, and
      CDw15O (SLAM). Here, we report the isolation and characterization of the Ly9
      gene, which encompasses at least 19 kb and contains ten separated exons, with
      sizes ranging from 54 to 355 bp. Each Ig-like domain is encoded by an individual
      exon. Sequence analysis of a 1.5-kb fragment upstream from the start
      translational codon revealed the absence of appropriately located TATA and CAAT
      boxes. However, potential binding sites for the transcription factors PU.1,
      Ikaros, AP-1, GATA-2, NF-GMa, NFAT-1, and Oct-2, which are involved in the early
      development and maturation of lymphocytes, were found. To further characterize
      the two allotypes of Ly9, cDNA of Balb/C and C57BL/6 mouse strains were sequenced
      and the predicted polypeptides compared. Nine discrepancies were found, four of
      them in the first Ig-like domain. The characterization of the genomic
      organization of Ly9 presented in this paper may improve understanding of the
      molecular mechanisms that regulate Ly9 expression, and the production of a
      construct to disrupt the Ly9 gene in ES cells in order to produce deficient mice.

PMID- 10970094
TI  - H2-M, a facilitator of MHC class II peptide loading, and its negative modulator
      H2-O are differentially expressed in response to proinflammatory cytokines.
AB  - H2-M is a major histocompatibility complex (MHC) class II-like molecule that
      catalyzes peptide binding to MHC class II molecules. Recently, the H2-O
      heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been
      shown to be physically associated with H2-M in B cells and to downregulate H2-M
      function. Examination of H2-O expression in freshly isolated mouse organs
      revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid
      and nonlymphoid tissues. To evaluate the gene regulation and functional impact of
      H2-O on antigen presentation, we examined the effects on MHCII, invariant chain
      (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and interferon
      (IFN)-gamma in different antigen-presenting cells (APCs). In nonprofessional
      APCs, e.g., L929 fibroblasts, IFN-gamma-inducible expression of the MHC class II
      specific transcription factor CIITA is associated with coordinate expression of
      MHCII, Ii, H2-M, and H2-Oa genes but without concomitant H2-Ob induction. In
      contrast, professional APCs, e.g., the macrophage cell line P388D1, exhibit
      constitutive H2-Oa and H2-Ob expression, which is not inducible by IFN-gamma in
      contrast to CIITA, MHCII, Ii, and H2-M expression. In B cells, CIITA, MHCII, Ii,
      and H2-M genes are differentially expressed relative to H2-Oa and H2-Ob genes
      upon stimulation with IL-4, IL-10, or IFN-gamma. A differential ratio of H2-M to
      H2-O may represent one mechanism by which professional and nonprofessional APCs
      bypass H2-O inhibitory activity.

PMID- 10970095
TI  - Genomic organization and characterization of mouse SAP, the gene that is altered
      in X-linked lymphoproliferative disease.
AB  - X-linked lymphoproliferative (XLP) disease is a fatal immunological disorder that
      renders the immune system unable to respond effectively to Epstein-Barr virus
      (EBV) infection. The gene that encodes a protein termed SAP or SH2D1A is either
      deleted or mutated in XLP patients, resulting in uncontrolled B- and T-cell
      proliferation upon EBV infection. Here, we report the cloning and
      characterization of the mouse SAP gene. It is localized on the mouse X chromosome
      and comprises four exons spanning approximately 25 kb. Its expression appears to
      be restricted to T lymphocytes. Whereas a high level of SAP expression is
      observed in Thl cells, only small amounts are detectable in Th2 cells. Moreover,
      SAP expression is down-regulated upon in vitro activation of T cells, including
      CD4+, CD8+ single-positive T cells, and Thl and Th2 cells. This study provides
      valuable information for in-depth genetic and biochemical analysis of the
      function of SAP in the immune system.

PMID- 10970097
TI  - Physical mapping and evolution of the centromeric class I gene-containing region
      of the rat MHC.
AB  - We physically mapped the centromeric part of the BN rat MHC (RT1n haplotype) in a
      contig of overlapping P1-derived artificial chromosome (PAC) clones encompassing
      about 300 kb. The following genes were identified and ordered as: (Syngap, Hset,
      Daxx, Bing1)-Tapbp-Rgl2-Ke2-Bing4-B3galt4- Rps18-Sacm2l-RT1-A1-RT1-A2-RT1-A3
      Ring1-Ring2-++ +Ke4-Rxrb-Col11a2-RT1-Hb-Ring3-RT1-DMb. Thus, in contrast to other
      RT1 haplotypes, RT1n contains three class I genes, RT1-A1, RT1-A2, and RT1-A3,
      mapping between the Sacm2l and Ring1 genes. Comparisons of the sequences flanking
      the Sacm2L and Ring1 genes in rat, human, and mouse suggest that the class I gene
      containing region was inserted between these genes in rat and mouse at a similar
      position. Thus, this insertion is likely to have occurred in a common ancestor of
      these rodents, although the presence of a site particularly permissive for
      insertions cannot be excluded.

PMID- 10970096
TI  - An automated prediction of MHC class I-binding peptides based on positional
      scanning with peptide libraries.
AB  - Specificities of three mouse major histocompatibility complex (MHC) class I
      molecules, Kb, Db, and Ld, were analyzed by positional scanning using
      combinatorial peptide libraries. The result of the analysis was used to create a
      scoring program to predict MHC-binding peptides in proteins. The capacity of the
      scoring was then challenged with a number of peptides by comparing the prediction
      with the experimental binding. The score and the experimental binding exhibited a
      linear correlation but with substantial deviations of data points. Statistically,
      for approximately 80% of randomly chosen peptides, MHC-binding capacity could be
      predicted within one log concentration of peptides for a half-maximal binding.
      Known cytotoxic T-lymphocyte epitope peptides could be predicted, with a few
      exceptions. In addition, frequent findings of MHC-binding peptides with
      incomplete or no anchor amino acid(s) suggested a substantial bias introduced by
      natural antigen processing in peptide selection by MHC class I molecules.

PMID- 10970098
TI  - Genomic structure and sequence of the leukocyte common antigen (CD45) from the
      pufferfish Fugu rubripes and comparison with its mammalian homologue.
AB  - The leukocyte common antigen (CD45) is a transmembrane protein tyrosine
      phosphatase expressed only in nucleated hematopoietic cells. It can be expressed
      as different isoforms depending on the cell type and the state of activation or
      differentiation and it is known to play a crucial role in the maturation and
      differentiation of B and T lymphocytes. However, the regulation of CD45
      expression and function has been difficult to study due to the complexity of the
      gene in mammals. In this paper, we report the isolation and characterization of a
      CD45 orthologue gene from the Japanese pufferfish Fugu rubripes (Fugu). The Fugu
      CD45 cDNA sequence contains an open reading frame of 1,246 amino acids with a
      variable extracellular region as a result of the alternative splicing of two
      exons. The intracellular region is organized into two highly conserved tyrosine
      phosphatase domains. The extracellular region is not conserved except in some
      structural domains. The Fugu CD45 gene has a similar exon/intron organization to
      that of mammals except in the 5' end where some exons are missing or fused
      together. By contrast, the gene is ten times smaller in Fugu due to the small
      size of the introns. These studies show a greater flexibility to evolve at the 5'
      end of the gene and provide clues to the functionally important domains of the
      molecule. In addition, the lower complexity of this gene in Fugu should allow
      easier mapping of its regulatory sequences.

PMID- 10970099
TI  - Multiple forms of alpha2-macroglobulin from a bony fish, the common carp
      (Cyprinus carpio): striking sequence diversity in functional sites.
AB  - Unlike mammals, bony fish possess multiple genes encoding the complement
      component C3, a member of the alpha2-macroglobulin (alpha2M) protein family,
      presumably expanding the diversity of immune recognition. To examine whether the
      alpha2M gene has also duplicated and diverged in the bony fish lineage, cDNA
      cloning of alpha2M from a pseudotetraploid teleost, the common carp (Cyprinus
      carpio), was conducted and resulted in the isolation of three distinct alpha2M
      sequences from a single individual, indicating the presence of multiple alpha2M
      genes in this species. The deduced amino acid sequences contained a post
      translational cleavage signal, predicting a C3-like two-chain structure, as in
      lamprey alpha2M. Two distinct alpha2M proteins were purified from carp serum;
      both proved to be Mr 380,000 dimers, the subunits of which are composed of
      disulfide-linked alpha chains (Mr 93,000) and beta chains (Mr 85,000), as
      reported for the alpha2M from plaice, another teleost species. The presence of an
      internal thioester in the alpha chain was demonstrated by its autolytic
      fragmentation and direct incorporation of [14C]methylamine. Interestingly, the
      three forms of carp alpha2M exhibited outstanding sequence diversity in the bait
      region which displays target sequences for various proteases, and in the C
      terminal region of the alpha chain assigned as the receptor-binding domain, while
      an Asn residue at the position corresponding to the catalytic His in C3 was
      completely conserved in the carp alpha2Ms, as in most alpha2Ms of other animals.
      The possible functional significance of the sequence diversity is discussed.

PMID- 10970100
TI  - Evolutionary history of the Rh blood group-related genes in vertebrates.
AB  - Rh and its homologous Rh50 gene products are considered to form heterotetramers
      on erythrocyte membranes. Rh protein has Rh blood group antigen sites, while Rh50
      protein does not, and is more conserved than Rh protein. We previously determined
      both Rh and Rh50 gene cDNA coding regions from mouse and rat, and carried out
      phylogenetic analyses. In this study, we determined Rh50 gene cDNA coding regions
      from African clawed frog and Japanese medaka fish, and examined the long-term
      evolution of the Rh blood group and related genes. We constructed the
      phylogenetic tree from amino acid sequences. Rh50 genes of African clawed frog
      and Japanese medaka fish formed a cluster with mammalian Rh50 genes. The gene
      duplication time between Rh and Rh50 genes was estimated to be about 510 million
      years ago based on this tree. This period roughly corresponds to the Cambrian,
      before the divergence between jawless fish and jawed vertebrates. We also BLAST
      searched an amino acid sequence database, and the Rh blood group and related
      genes were found to have homology with ammonium transporter genes of many
      organisms. Ammonium transporter genes can be classified into two major groups
      (amt alpha and amt beta). Both groups contain genes from three domains (bacteria,
      archaea, and eukaryota). The Rh blood group and related genes are separated from
      both amt alpha and beta groups.

PMID- 10970101
TI  - A revised sequence of the human beta7 integrin gene (ITGB7) promoter region
      obtained by inverse PCR.

PMID- 10970102
TI  - The peptide-binding motif of HLA-B*3505.

PMID- 10970103
TI  - TGFB1 gene polymorphisms and inflammatory bowel disease.

PMID- 10970104
TI  - Promoter structures suggest independent translocations of ancestral rat RT1.A and
      mouse H2-K class I genes.

PMID- 10970106
TI  - A functional role for the Y box in regulating an MHC class II B gene promoter in
      chicken lymphocytes.

PMID- 10970105
TI  - Cloning and sequencing of the horse and sheep high-affinity IgE receptor alpha
      chain cDNA.

PMID- 10970107
TI  - Ultrasonography of peripheral nerves.
AB  - During sonographic examination of the extremities using high frequency "small
      parts" equipment, peripheral nerves may be identified in virtually all patients.
      Peripheral nerves have a typical ultrasonographic pattern that correlates well
      with histologic structure and facilitates differentiation between nerves and
      tendons. The ability of this technique to depict peripheral nerves makes it
      possible, in many instances, to study nerve abnormalities in trauma, entrapment
      syndromes and tumors. Ultrasound can enable differentiation of an endoneural from
      an extraneural space-occupying lesion and evaluation of the extent and
      consistency of the lesion, as well as the integrity and dynamic behavior of the
      nerve involved at follow-up study. The purpose of this review article is to
      describe the normal ultrasonographic appearance of peripheral nerves and to
      discuss the potential role of this technique to image nerve lesions
      noninvasively. A series of paradigmatic ultrasound images of diverse pathologic
      processes involving peripheral nerves is presented. Although the ultrasound study
      of peripheral nerves remains in its infancy, with further refinement of
      ultrasound technology and a more precise knowledge of the ultrasound appearance
      of the extremities we may be optimistic to the future impact of this technique on
      diagnosis, treatment and prognosis in patients clinically suspected to have a
      nerve lesion.

PMID- 10970108
TI  - Molecular genetics of familial amyloidotic polyneuropathy.

PMID- 10970109
TI  - Pain relief by various kinds of interference stimulation applied to the
      peripheral skin in humans: pain-related brain potentials following CO2 laser
      stimulation.
AB  - Pain perception is changed by various kinds of interference stimulation applied
      to the peripheral skin in humans. We investigated pain-related somatosensory
      evoked brain potentials (pain SEPs) following CO2 laser stimulation applied to
      the hand or foot in normal subjects, to elucidate the underlying mechanisms. A
      pain visual analogue scale (VAS) was also scored to determine the degree of
      subjective feeling of painful sensation. The following stimulations were applied
      as the interference: (1) vibration, (2) active and passive movements of the hand
      or foot, (3) noxious warming by hot water (46 degrees C) and (4) noxious cooling
      by ice water (0 degrees C). These interference stimulations were applied not only
      to the same hand or foot as the laser stimuli but also to the contralateral hand
      or foot. Significant changes in the amplitude of pain SEPs and VAS score were
      observed to some degree for each type of interference, and we concluded that gate
      control theory and diffuse noxious inhibitory control were the most appropriate
      hypotheses to account for this particular phenomenon of pain relief. Some
      movement-related cortical activities were also considered to be an important
      factor. These findings could not be accounted for by simple changes in the
      subjects' attention. Pain relief was more prominent at the second pain ascending
      through C fibers than that of the first pain ascending through Adelta fibers. The
      responsible sites for this phenomenon are considered to be the dorsal horn of the
      spinal cord, the brainstem and some parts of the brain such as the second sensory
      cortex and the cingulate cortex.

PMID- 10970110
TI  - Regeneration of putative sensory and sympathetic cutaneous nerve endings in the
      rat foot after sciatic nerve injury.
AB  - The present study examines the occurrence of calcitonin gene-related peptide-,
      substance P- and tyrosine hydroxylase-like immunoreactive profiles in glabrous
      and hairy foot skin from normal and nerve-injured rats. After neurotomy/suture,
      glabrous skin samples contain few calcitonin gene-related peptide-, substance P-
      and tyrosine hydroxylase-like immunoreactive profies. The number of calcitonin
      gene-related peptide- and substance P-like immunoreacive profiles in the
      epidermis is significantly subnormal. Hairy skin from these rats does also
      contain few calcitonin gene-related peptide-, substance P- and tyrosine
      hydroxylase-like immunoreactive profiles. In addition, the presence of epidermal
      calcitonin gene-related peptide-like imunoreactive profiles in glabrous skin is
      subnormal on the contralateral side. After nerve crush injury, the occurrence of
      calcitonin gene-related peptide-like, but not substance P-like, immunoreactive
      profiles in th epidermis of the glabrous skin is significantly subnormal. The
      occurrence of tyrosine hylase-like immnunoreactive fibres in relation to the
      digital artery is also subnormal. The occurrence in hairy skin of calcitonin gene
      related peptide-like immunoreactive, substance P-like immunoreactive and tyrosine
      hydroxylase-like immunoreactive profiles is subnormal. In both skin types, the
      contralateral occurrence of such profiles is subjectively normal. These results
      show that the occurrence of calcitonin gene-related peptide-, substance P-, and
      tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin
      is clearly subnormal after neurotomy and suture and less abnormal after nerve
      crush. After neurotomy and suture the contralateral side is also affected.

PMID- 10970111
TI  - Expression of type I and III collagen and laminin beta1 after rat sciatic nerve
      crush injury.
AB  - Extracellular matrix changes are thought to be essential to the regeneration of
      peripheral nerves. The production of this matrix is believed to be regulated by
      interactions between axons and their supporting cells. In this study matrix
      production and cell proliferation were studied during rat sciatic nerve
      regeneration after a crush injury, and compared to that after rat sciatic nerve
      transection. Expression of proalpha1(I) and proalpha1(III) collagen and laminin
      beta1 mRNAs was followed in isolated endoneuria by Northern and in situ
      hybridization both proximally and distally to the site of either a crush injury
      or transection of rat sciatic nerve up to 18 weeks. Changes in the Schwann cell
      and fibroblast populations were monitored by morphometric analysis of endoneurial
      cross-sections immunostained for S-100 protein. The process of axonal
      regeneration was followed by Bielschowsky's silver staining. A crush injury
      initially resulted in increased expression of all mRNAs studied in the
      endoneurial cells. However, with progressing axonal regeneration the amount of
      collagen mRNAs returned to control levels, whereas the amount of laminin beta1
      mRNA in the distal site of the crush remained elevated throughout the study
      period. The expression of type I collagen mRNA was enhanced after nerve
      transection injury compared to that after the crush injury. The epineurial
      fibroblasts actively expressed both type I and III collagen mRNAs after the
      injury. The proliferation of Schwann cells and the expression of collagen mRNAs
      are not, at least directly, related to the axonal regeneration. However, the long
      lasting and strong expression of laminin beta1 mRNA after a nerve crush injury
      may be related to good axonal regeneration. The expression of type I collagen in
      the epineurium may lead to clinically well-recognized epineurial scarring and
      thus impede axonal regeneration.

PMID- 10970113
TI  - Molecular approaches towards the isolation of tyrosine phosphatases expressed in
      the peripheral nervous system.
AB  - Protein tyrosine phosphatases (PTP) are increasingly appreciated to play a
      crucial function in the development, homeostasis and regeneration of the nervous
      system. In an attempt to determine the set of PTPs that are expressed in the PNS,
      we have employed polymerase chain reaction (PCR)-based strategies. Degenerate
      oligonucleotide primers which were designed based on PTP-consensus motifs were
      used on substrate cDNAs derived from sciatic nerves of either 3, 10 or 60 days
      old rats as well as from cultured rat Schwann cells. The resulting partial PTP
      clones were used for low-stringency hybridization screening of a cDNA library
      constructed from the sciatic nerves of 7 to 8 days-old rats. The combined
      approaches yielded three known rat PTPs and at least three potential rat species
      homologues of previously identified mouse PTPs. Furthermore, several partial
      clones encoding potentially novel PTPs have been isolated. The suitability of our
      experimental approaches for the identification and characterization of PNS
      expressed PTPs will be discussed.

PMID- 10970112
TI  - Muscle reinnervation in hypothyroid rats.
AB  - Reinnervation of extensor digitorum longus muscle following crush of sciatic
      nerve was studied in rats made hypothyroid after weaning. In vitro intracellular
      recordings of muscle cell postsynaptic potentials were carried out; moreover
      twitch and tetanus following direct muscle stimulation and nerve stimulation were
      recorded. Frequency of miniature end-plate potentials (mepps) may be regarded as
      an index of presynaptic mechanism in regenerated nerve endings: when regenerating
      axons reach the muscle, the frequency of spontaneous acetylcholine quantal
      release is very low and increases in subsequent weeks. No significant differences
      were noted in miniature end-plate potential frequency between muscles of normal
      and hypothyroid rats at the same time from denervation; mepp amplitude was higher
      in hypothyroids, in accordance with the smaller muscle fibre diameters.
      Regenerating nerve fibres entering the muscle extensively sprout, giving rise to
      a number of nerve endings which exceeding the number of muscle cells, are
      subsequently withdrawn; correspondingly, muscle cells are transiently
      polyinnervated and the number of polyinnervated muscle cells peaks decreases
      subsequently approximating zero. The percentage of polyinnervated cells peaked
      sooner in hypothyroid rats than in controls and afterwards decreased; a tail of
      polyinnervation was found at long term. Tension recording experiments showed a
      shorter time of reinnervation of muscles in hypothyroid rats, but no difference
      in regeneration rate could be argued. These findings suggest an influence of
      thyroid hormones in the stabilization of motor innervation of reinnervated
      muscle, but not in nerve regeneration process.

PMID- 10970114
TI  - Unusual ultrastructural features in intrafascicular ganglion cells of the rat
      pelvic nerve.
AB  - The incidental finding of four ectopic ganglion cells within the pelvic nerve of
      a normal rat prompted a thorough electron microscopic investigation of the
      ultrastructural features of these neurons. They were found to enwrap presynaptic
      terminals inside crater-like invaginations; the appositional surfaces were made
      more complex by the presence of slender dendritic appendages and sheet-like
      processes of glial cells. The presynaptic elements contained both clear and dense
      cored vesicles, and appeared similar to those characterizing SIF (paraneuronal)
      cells. In addition, cilia were encountered in both the invaginated processes and
      most of the Schwann cells associated with the pre- and postsynaptic nerve cells
      and their processes. Overall, these features were deemed worth reporting because
      1) of the unusual features of synaptic input from a SIF cell to a ganglion cell
      associated with the pelvic plexus, and 2) the ectopic ganglion cells possibly
      represent the sole example, other than ciliary neurones in the avian ciliary
      ganglion, of postsynaptic cells encasing presynaptic endings inside their
      perikarya.

PMID- 10970115
TI  - Vanilloid-sensitive neurons: a fundamental subdivision of the peripheral nervous
      system.

PMID- 10970116
TI  - The functional recovery of muscle proprioceptors after peripheral nerve lesions.

PMID- 10970117
TI  - Critical illness polyneuropathy, facts and controversies.

PMID- 10970119
TI  - Expression of laminin and collagen genes by cells cultured from developing human
      sciatic nerves.
AB  - The expression of laminin alpha1, alpha2, beta1, beta2 and gamma1 subunits and
      proalpha1(I), proalpha1(III), alpha1(IV), alpha1(VI), alpha2(VI) and alpha3(VI)
      collagen chains was studied by Northern hybridizations, RNase protection assays
      and indirect immunofluorescence (IIF) labellings in cell cultures initiated from
      sciatic nerves of 14-27-wk-old human fetuses. The cultures represented mixed
      populations of Schwann cells, perineurial cells and fibroblasts, as estimated by
      morphology and S 100 protein immunolabellings. The mRNAs for certain basement
      membrane (BM) components, laminin beta1 and gamma1 chains and collagen alpha1(IV)
      chain, were readily detectable by Northern analyses in all cultures. In contrast,
      laminin alpha1, alpha2 and beta2 chain mRNAs were expressed at markedly lower
      levels. The expression of laminin alpha1 chain was detectable only by RNase
      protection assay. RNase protection analysis also demonstrated that the expression
      of laminin alpha2 chain increased with the developmental stage of the nerve used
      as the source for cell cultures. The expression of laminin beta2 chain was
      detected only at the protein level by IIF which demonstrated a faint immunosignal
      in a small subpopulation of cells. The mRNAs for type I, III and VI collagens
      were readily detectable in the cultures by Northern hybridizations. In summary,
      the extracellular matrix genes expressed in fetal human peripheral nerves and
      corresponding cell cultures display marked similarities. Cell cultures
      characterized here may prove useful in analyses elucidating potential roles of
      selected growth factors and cytokines in the induction of e.g. laminin alpha1 and
      beta2 chain expression by cells of developing peripheral nerves.

PMID- 10970118
TI  - Palmitoylation of myelin P0 protein is independent of its synthesis and parallels
      that of phospholipids.
AB  - To determine whether the acyl chains modifying P0, the major protein of PNS
      myelin, turn over independently of the protein backbone, sciatic nerve slices
      from 10 to 65 day-old rats were incubated with a mixture of [3H]palmitic acid and
      [14C]amino acids, and proteins were analyzed by electrophoresis. Incorporation of
      [14C]amino acids into nerve P0 decreased approximately 10-fold between 10 and 65
      days of age. In contrast, palmitoylation of P0, although maximal at 10 days-of
      age, decreased only 3-4-fold during the same period. In the same experiments, the
      incorporation of [3H]palmitate into the nerve and into various lipids classes
      diminished by a comparable extent (2.5-fold). Thus, if corrected by the uptake of
      the tritiated precursor, palmitoylation of P0 remains nearly constant throughout
      development, and it is therefore independent of protein synthesis. Preincubation
      of nerve slices with cycloheximide for one hour reduced the incorporation of
      [3H]palmitate into both P0 and phospholipids in a concentration-dependent manner.
      At 10 microM cycloheximide, palmitoylation of P0 was unaffected while its
      synthesis was still repressed, indicating that these events are uncoupled. The
      effect of cycloheximide on fatty acid uptake can be attributed to inhibition of
      the palmitoyl-CoA : lysophosphatidylcholine acyltransferase activity. Neither the
      distribution of palmitate between albumin and lipid membranes nor the activities
      of other lipid-metabolizing enzymes were affected by the inhibitor. In
      conclusion, these results indicate that P0 palmitoylation occurs mainly on the
      preexisting molecules, and it therefore constitutes a dynamic event.

PMID- 10970120
TI  - Peripheral nerve regeneration through bioresorbable and durable nerve guides.
AB  - We compared reinnervation of target organs after sciatic nerve resection and
      repair by tubulization with biodurable tubes of silicone and teflon, or
      bioresorbable nerve guides of collagen and poly(L-lactide-co-6-caprolactone)
      (PLC) leaving a 6 mm gap in different groups of mice. All tubes were of 1 mm
      inside diameter and thin-walled (50 to 250 microm). Functional reinnervation was
      assessed by noninvasive methods to determine recovery of sweating, sensory and
      motor functions in the hindpaw repeatedly during 5 months postoperation. PLC
      guides allowed faster and higher levels of reinnervation for the four functions
      tested than collagen and silicone tubes, while teflon tubes gave the lowest
      levels of recovery. Regenerative reinnervation by thin nociceptive and sudomotor
      fibers was higher than by large sensory and alphamotor fibers in all groups.
      Resorbable tubes promoted regeneration in a higher proportion of mice than
      durable tubes. In cases with effective regeneration the nerve cable was
      multifascicular, with mild to moderate mononuclear cell infiltrates and a thin
      newly formed perineurium. The number of myelinated fibers was higher in PLC and
      silicone tubes than in collagen and teflon tubes. There was only minimal
      inflammatory reaction within the remnants of collagen tubes, but not in the other
      materials. PLC tubes of slow reabsorption rate seem useful for repairing long
      gaps in injured nerves.

PMID- 10970121
TI  - Down-regulation of evoked synaptic release in rat neuromuscular junction.
AB  - Spontaneous and evoked synaptic transmission were studied at the rat extensor
      digitorum longus (EDL) neuromuscular junction in the presence of CGIIIA mu
      conotoxin, a peptide which suppresses action potential in the sarcolemma, while
      not affecting impulse conduction along motor nerve fibers. The binomial
      parameters m (mean quantal content) and n (number of units involved in evoked
      quantal release) increased as a function of extracellular Ca++ ([Ca++]o), up to
      the physiological concentration (2 mM). Additional Ca++ failed to induce a
      statistically significant increase in either m or n, while the probability of
      activation (p) did increase, approaching unity at 4 mM [Ca++]o. In cut EDL
      preparations, without CGIIIA, the relation between end-plate potential amplitude
      and [Ca++]o resembled that for quantal content in unlesioned, CGIIIA-treated
      muscles. In contrast, normal preparations exposed to 0.5 mg/ml d-tubocurarine
      were much more responsive to Ca++ variations, with a significant end-plate
      potential amplitude increase in the presence of 4 mM [Ca++]o. However, in
      curarized preparation the evoked release was remarkably affected by repetitive
      stimulation, while in the absence of postsynaptic blockers release levels were
      more stable. We suggest that the stimulatory effect of extracellular Ca++ on
      evoked release at the mammalian neuromuscular junction might normally be
      depressed under physiological conditions, possibly by a down-regulation mechanism
      involving presynaptic nicotinic receptors. Such inhibition would increase nerve
      transmission efficiency during prolonged motor terminal activity.

PMID- 10970122
TI  - Wire mesh as a post-operative physiotherapy assistive device following peripheral
      nerve graft repair in the rat.
AB  - Traditional methods of assessing nerve recovery following injury, including
      histomorphometry and electrophysiology, do not necessarily correlate with return
      of motor and sensory function. Accordingly, many investigators have used walking
      track analysis as an assessment of global functional recovery following sciatic,
      peroneal or tibial nerve injury. However, walking track reliability may be
      compromised by the development of flexion contractures secondary to neurologic
      loss. To prevent this, regular manual physiotherapy is recommended which is a
      time-consuming and often frustrating process for both the animal and
      investigator. We report the use of a wire mesh as a simple post-operative
      assistive device to provide constant physiotherapy. Twelve Lewis rats were
      randomized to one of two experimental groups. Each rat received a 2 cm posterior
      tibial nerve autograft. Postoperatively, animals in group 1 received manual
      physiotherapy, consisting of repeated flexion and extension exercises of the
      ankle, knee and hip every two weeks. Group 2 rats were permitted to climb freely
      on a 30 x 18 cm piece of wire mesh placed at a 45 degree angle within their cage.
      Group 2 rats received no manual physiotherapy throughout the course of the study.
      Serial walking tracks were performed every four weeks until sacrifice at sixteen
      weeks. There was no development of flexion contractures in the injured hind limbs
      of either group. There was no morbidity such as blisters associated with the use
      of the wire mesh. There was no statistical difference in walking track recovery
      between groups at any time period. However, a trend towards better functional
      recovery was seen in the group receiving constant physiotherapy via the wire
      mesh. The use of a wire mesh as a post-operative assistive device is an
      inexpensive, simple and reliable method to provide continuous physiotherapy to
      animals following denervation.

PMID- 10970123
TI  - Innervation of lumbar intervertebral disks--a review.

PMID- 10970124
TI  - Immunohistochemical localization of S100 proteins in dorsal root, sympathetic and
      enteric ganglia of several mammalian species, including man.
AB  - The occurrence of S100 proteins in neurons of the mammalian peripheral nervous
      system is still controversial. This study was designed to investigate this topic
      in dorsal root ganglia (DRG) and the enteric nervous system (ENS) of several
      mammalian species (horse, buffalo, cow, sheep, pig, dog, rabbit and rat), as well
      as in DRG, paravertebral sympathetic ganglia (SG) and ENS of the adult man. Rat
      embryos of E17 and E19 were also examined. The material was fixed in Bouin's
      fixative, paraffin-embedded and processed for immunohistochemistry, combined with
      image analysis, using a panel of mono and polyclonal antibodies against
      S100alpha, S100beta or S100alpha + beta (referred to here as S100) proteins. In
      all species examined, strong S100 protein immunoreactivity (IR) was found in
      satellite glial cells and Schwann cells, which also showed S100alpha and S100beta
      IR in humans. Furthermore, faint S100 protein IR was observed in a subpopulation
      of DRG intermediate- and large-sized sensory neurons in humans, buffalo, sheep,
      and pig. The rat was the only species showing clear S100 and S100beta in neurons,
      labelling in about 30-35% in adults (small, intermediate and large in size), and
      about 88% at E17 and 42% at E19, respectively. Weak S100alpha protein IR was
      observed in most of human SG neurons. In ENS, S100 protein IR was restricted to
      enteric glial and Schwann cells, with the exception of cow and goat in which a
      subset of neurons in both the myenteric and submucous plexuses displayed strong
      S100 protein IR. Neuronal S100alpha IR and glial S100beta IR was found in the
      human ENS. The present results demonstrate intra- and inter-specific differences
      in the expression of S100 proteins by neurons of the peripheral nervous system
      among mammalian species. Furthermore, they also suggest that neuronal S100
      protein, at least in humans, consists of both S100alpha and S100beta.

PMID- 10970125
TI  - Electron microscopial localization of 5'-nucleotidase in the rat peripheral nerve
      fibers by cerium-based cytochemistry.
AB  - To extend our earlier studies on the subcellular distribution of 5'-nucleotidase
      in peripheral nerve fibers, we have applied the cytochemical method with cerium
      ions as trapping agents for inorganic phosphate released from adenosine-5'
      monophosphate. Adult and 15-day-old Wistar rats were investigated. In myelinated
      nerve fibers, 5'-nucleotidase activity was visualized mainly on the Schwann cell
      plasma membrane, the axolemma, the surface of the myelin sheath and its widened
      lamellae in the paranodal areas, and Schmidt-Lanterman clefts. Single reaction
      precipitates were observed at the intraperiod lines of the compact myelin. In
      addition, in the young animals, the nuclear envelope and the rough endoplasmic
      reticulum were also found associated with reaction deposits. The simple axon
      Schwann cell sheaths of the unmyelinated nerve fibers were also reactive. The
      cerium-based method reveals a pattern of localization of the 5'-nucleotidase in
      peripheral nerve fibers quite similar to that detected by the conventional lead
      based method. The cerium-based method, however, determines a more uniform
      distribution of finer reaction deposits along the cellular membranes. In young
      rats, the enzyme reaction was found to be more intense, especially in the areas
      of myelin-forming membranes.

PMID- 10970126
TI  - Morphometric evaluation of paraneoplastic neuropathies associated with
      carcinomas, lymphomas, and dysproteinemias.
AB  - Paraneoplastic peripheral neuropathies are caused by indirect effects of
      carcinomas, mainly small cell bronchogenic carcinomas, lymphoproliferative
      disorders (lymphomas, myelomas, polycythemia vera), and dysproteinemias (benign
      monoclonal paraproteinemia, Waldenstrom's macroglobulinemia) including
      cryoglobulinemias. Those associated with carcinomas are usually considered as
      severe, those associated with benign gammopathies (monoclonal gammopathies of
      unknown significance, MGUS) as mild, and those with cryoglobulinemias as of
      variable severity. In a larger series of 104 autopsy and biopsy cases, we noted a
      wide range of severity concerning various morphometric parameters of peripheral
      nerve fibers by evaluating sural nerves. There were no apparent morphometric
      differences between the groups of disorders. The most valuable parameter of optic
      electronic evaluation and comparison turned out to be the myelin area expressed
      as a percentage of the endoneurial area because this measure comprises the
      relative number, size, and myelin thickness of the myelinated nerve fibers. In
      the 104 cases of the three disease groups, most of the cases (38 cases; 36.5%)
      showed a moderate reduction of the myelin sheath area per endoneurial area of
      sural nerves. This was followed by 34 cases (32.7%) with severe and very severe
      reduction. Twenty-nine cases (27.9%) presented with mild reduction. It is
      concluded that the severity of the neuropathy depends largely on the stage of the
      disease and the time of progression rather than on the type of the underlying
      disorder.

PMID- 10970127
TI  - Modifications of afferent activities from Tibialis anterior muscle in rat by
      tendon vibrations, increase of interstitial potassium or lactate concentration
      and electrically-induced fatigue.
AB  - Although previous experiments with a partially similar objective have been
      described in dogs, cats and rabbits, the purpose of this study was to identify
      and characterize mechanosensitive and chemosensitive muscle afferents in the
      anaesthetized rat since it is a widely used laboratory animal. The peroneal nerve
      innervating the tibialis anterior muscle was studied. Measurement of conduction
      velocities from compound action nerve potentials evoked by peripheral nerve
      stimulation allowed identification of group I-II (10.79+/-1.02 m/s), group III
      (2.96+/-0.58 m/s) and group IV (0.46+/-0.07 m/s) afferent fibers. Computation of
      the different compound potential areas showed that afferents I and II arising
      from spindles and tendon organs represented 9.65+/-2.2%, whereas afferents III
      and IV arising from free nerve endings in muscle represented 90.35+/-2.2% (III,
      46.66+/-2.71% and IV, 43.69+/-2.52%). Action potentials were recorded from teased
      nerve filaments. Mechanical tendon vibrations (10 to 90 Hz) were used to activate
      mechanoreceptors. Peak increase in afferent discharge (fimpulses) was measured at
      50 Hz (n = 12/19 units) or 70 Hz (n = 7/19 units). Intra-arterial bolus
      injections of different concentrations of potassium chloride (KCl: 1 to 20 mM) or
      lactic acid (LA: 0.5 to 3 mM) elicited marked activation of III and IV afferents
      (n = 124). Enhancement of fimpulses was not proportional to the increase in [KCl]
      or [LA]. Activation of afferents plateaued when [KCl] was equal or greater than 5
      mM while fimpulses peaked, then decreased, when [LA] was 1 mM. Muscle fatigue
      induced by direct electrical muscle stimulation (EIF) markedly activated group
      III-IV (n = 17/18) afferents (176.9+/-29.7% of control) which persisted for the 3
      minutes of recovery from fatigue. Maximal fimpulses increases in response to LA
      (+67%) and KCl (+46.9%) injections and to EIF (+76.9%) were similar. This
      procedure for characterizing the functional properties of sensory nerve endings
      in a skeletal muscle may be used to assess further changes in sensory muscle
      paths in experimental rodent pathophysiological systems.

PMID- 10970128
TI  - The effect of exercise training on functional recovery after sciatic nerve crush
      in the rat.
AB  - Two separate experiments were carried out in order to evaluate the influence of
      moderate swim training and treadmill running on the rate of recovery of
      sensorimotor function following sciatic nerve injury in the rat. Nerve injury was
      induced by sciatic nerve crush. In the first experiment, rats were subjected to
      swim exercise (180 m daily), either for 7 days before, or for 14 consecutive days
      after nerve injury. In the second experiment rats were exercised on a motor
      driven treadmill device (10 m/min for 30 min twice daily) for 21 days. The
      recovery from nerve injury was assessed by means of an analysis of the free
      walking pattern (motor function) and the foot withdrawal reflex (sensory
      function) by electrical stimulation. The swim training program before or after
      crush did not affect the recovery of locomotor or sensory function. Treadmill
      running significantly deteriorated the gradual return of motor function (p <
      0.05), but did not influence sensory recovery. We conclude that swim training
      does not interfere with functional sensorimotor recovery after sciatic nerve
      injury, and that a mild program of treadmill running retards recovery. We
      hypothesize that the retardation of recovery as a result of treadmill running is
      the consequence of the stress inflicted by the negative reinforcement used in the
      treadmill, or due to the severity of the training. /O?>

PMID- 10970129
TI  - Medical students' attitudes at one school toward accident and emergency medicine
      as a career.

PMID- 10970130
TI  - Proficiency of PG-1 internal medicine residents in performing the pelvic
      examination.

PMID- 10970131
TI  - Classroom lectures do not influence family practice residents' learning.

PMID- 10970132
TI  - Intra-operative trans-oesophageal echocardiography is a potential source of
      sepsis in the intensive care.

PMID- 10970133
TI  - Haematological modifications after acute exposure to high altitude: possible
      implications for detection of recombinant erythropoietin misuse.

PMID- 10970134
TI  - All-trans retinoic acid and low-dose chemotherapy for acute promyelocytic
      leukaemia.

PMID- 10970135
TI  - MDR1 mRNA expression in young patients with acute lymphoblastic leukaemia.

PMID- 10970136
TI  - Pseudoautosomal linkage in chronic lymphocytic leukaemia.

PMID- 10970137
TI  - Bone marrow remission of hairy cell leukaemia induced by rituximab (anti-CD20
      monoclonal antibody) in a patient refractory to cladribine.

PMID- 10970138
TI  - Immunological effects of factor VIII concentrates: characterization of
      transforming growth factor beta as an immunomodulatory contaminant in factor VIII
      concentrates.

PMID- 10970139
TI  - On the mechanism of inhibition of factor VIIa by synthetic pentasaccharide, low
      molecular-weight heparins and unfractionated heparin.

PMID- 10970140
TI  - Cytokinesis: the art of partitioning.

PMID- 10970141
TI  - Institute of Biophysics "Carlos Chagas Filho" (IBCCF).

PMID- 10970142
TI  - Nervous system diseaes involving gap junctions.

PMID- 10970143
TI  - Tumor staging and classification in lung cancer. Summary of the international
      symposium. Madrid, Spain, 3-4 December 1999.

PMID- 10970144
TI  - Challenges, strategies and tools to optimize the management of ocular allergy.
      Proceedings of the 1st International Symposium. Monte Carlo, Monaco, June 22-25,
      1998.

PMID- 10970145
TI  - The birth of global ocular traumatology.

PMID- 10970146
TI  - [Vth Course on Current Concepts of Epilepsy. Santander, Spain, 16-18 February
      2000].

PMID- 10970149
TI  - A closer look at the postmenopausal bleeding uterus.

PMID- 10970148
TI  - Getting it right in prime time: tools and strategies for media interaction.

PMID- 10970147
TI  - Dual captures of Colorado rodents: implications for transmission of hantaviruses.
AB  - We analyzed dual-capture data collected during longitudinal studies monitoring
      transmission and persistence of Sin Nombre virus in rodents in Colorado. Our data
      indicate that multiple captures (two or more rodents captured in a single trap)
      may not be random, as indicated by previous studies, but rather the result of
      underlying, species-specific social behavior or cohesiveness. In the pairs we
      captured, most often, rodents were of the same species, were male, and could be
      recaptured as pairs. Therefore, dual captures of rodents, which are unusual but
      not rare, tend to occur among certain species, and appear to be nonrandom, group
      foraging encounters. These demographic and ecologic characteristics may have
      implications for the study of the transmission of hantaviruses.

PMID- 10970150
TI  - In memoriam Mirko Drazen Grmek (1924-2000).

PMID- 10970151
TI  - There is no motor redundancy in human movements. There is motor abundance.

PMID- 10970152
TI  - Control variables in mechanical muscle models: a mini-review and a new model.
AB  - A new mechanical model of isolated muscle is proposed in which spring with
      variable slack length is the force-generating element. Based on the review of
      experimental studies in isolated muscle, it is suggested that spring slack length
      Xo is the control variable in the model and is a function of motor unit firing
      rate. In the presence of sensory feedback, the Sliding Spring model is equivalent
      to the Rack and Pinion model. However, sensory feedback is essential in the Rack
      and Pinion model but complementary in the Sliding Spring model. How the new
      control variable in the model of isolated muscle affects the interpretation of
      control processes up the motor system hierarchy is discussed in light of certain
      controversies associated with the Lambda and Alpha models of control of movement.
      It is argued that the Sliding Spring model of isolated muscle can be used as a
      basis for developing models of control of movement.

PMID- 10970153
TI  - Excerpts from: On "tick paralysis" in sheep and man following bites of
      Dermacentor venustus. 1913.

PMID- 10970154
TI  - Grade the health of your county.

PMID- 10970155
TI  - Influenza vaccine shortages threaten those with chronic diseases.

PMID- 10970157
TI  - On the occurrence of true rolling of the eye about the line of sight. 2.

PMID- 10970156
TI  - Cyclosporin: nephro-protective as well as nephrotoxic?

PMID- 10970158
TI  - The binocular visual system in amblyopia.

PMID- 10970159
TI  - The cause of dissociated vertical deviation.

PMID- 10970160
TI  - Novel allele containing a 190C>T nonsynonymous substitution in the N
      acetyltransferase (NAT2) gene.
AB  - N-acetyltransferase (NAT2) is an enzyme involved in detoxification of various
      carcinogens. The gene is highly polymorphic with a number of alleles, and is also
      known as acetylator phenotypes: the fast, intermediate and slow acetylators. In
      this report, we describe a novel NAT2 allele, which was found in the allele
      typing with 109 Japanese individuals using conventional restriction fragment
      length polymorphism (RFLP) method. The sequence analyses of the entire amino acid
      coding region of the novel allele showed that it possessed a 190C>T variation
      leading to an amino acid substitution from arginine to tryptophan at position 64
      (R64W). Consequently, the novel allele we found has been given the name of
      NAT2*19 by the arylamine N-acetyltransferase nomenclature committee.

PMID- 10970161
TI  - Knotting of distal ventriculoperitoneal shunt tubing.

PMID- 10970162
TI  - Modelling production and cost efficiency within health care systems.

PMID- 10970163
TI  - Gibberellins 2000.

PMID- 10970164
TI  - Molecular physiology: engineering crops for hostile environments. Proceedings of
      a conference. Rothamsted, 14-16 December 1998.

PMID- 10970165
TI  - [Comment on V. Schumperlick et al.: Mesh in the abdominal wall].

PMID- 10970166
TI  - [The need for redon drainage in Lichtenstein hernia management].

PMID- 10970169
TI  - Financial incentives in recruitment of oocyte donors. The Ethics Committee of the
      American Society for Reproductive Medicine.

PMID- 10970167
TI  - Evidence for the role of environmental agents in the initiation or progression of
      autoimmune conditions.
AB  - The concordance of autoimmune disease among identical twins is virtually always
      less than 50% and often in the 25-40% range. This observation, as well as
      epidemic clustering of some autoimmune diseases following xenobiotic exposure,
      reinforces the thesis that autoimmune disease is secondary to both genetic and
      environmental factors. Because nonliving agents do not have genomes, disease
      characteristics involving nonliving xenobiotics are primarily secondary to host
      phenotype and function. In addition, because of individual genetic
      susceptibilities based not only on major histocompatibility complex differences
      but also on differences in toxin metabolism, lifestyles, and exposure rates,
      individuals will react differently to the same chemicals. With these comments in
      mind it is important to note that there have been associations of a number of
      xenobiotics with human autoimmune disease, including mercury, iodine, vinyl
      chloride, canavanine, organic solvents, silica, l-tryptophan, particulates,
      ultraviolet radiation, and ozone. In addition, there is discussion in the
      literature that raises the possibility that xenobiotics may also exacerbate an
      existing autoimmune disease. In this article we discuss these issues and, in
      particular, the evidence for the role of environmental agents in the initiation
      or progression of autoimmune conditions. With the worldwide deterioration of the
      environment, this is a particularly important subject for human health.

PMID- 10970168
TI  - Occupational exposure to crystalline silica and autoimmune disease.
AB  - Occupational exposure to silica dust has been examined as a possible risk factor
      with respect to several systemic autoimmune diseases, including scleroderma,
      rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel
      vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline
      silica, or quartz, is an abundant mineral found in sand, rock, and soil. High
      level exposure to respirable silica dust can cause chronic inflammation and
      fibrosis in the lung and other organs. Studies of specific occupational groups
      with high-level silica exposure (e.g., miners) have shown increased rates of
      autoimmune diseases compared to the expected rates in the general population.
      However, some clinic- and population-based studies have not demonstrated an
      association between silica exposure and risk of autoimmune diseases. This lack of
      effect may be due to the limited statistical power of these studies to examine
      this association or because the lower- or moderate-level exposures that may be
      more common in the general population were not considered. Experimental studies
      demonstrate that silica can act as an adjuvant to nonspecifically enhance the
      immune response. This is one mechanism by which silica might be involved in the
      development of autoimmune diseases. Given that several different autoimmune
      diseases may be associated with silica dust exposure, silica dust may act to
      promote or accelerate disease development, requiring some other factor to break
      immune tolerance or initiate autoimmunity. The specific manifestation of this
      effect may depend on underlying differences in genetic susceptibility or other
      environmental exposures.

PMID- 10970171
TI  - Re: The reincarnation of an old question.

PMID- 10970170
TI  - The re-incarnation of an old question--clomid effect on oocyte and embryo?

PMID- 10970172
TI  - More to ovarian transplantation than meets the eye.

PMID- 10970174
TI  - [Tree of life and tree of knowledge].

PMID- 10970173
TI  - [Should one perform renal biopsy in the elderly in nephrotic syndrome?].

PMID- 10970175
TI  - Focus on cluster headache: recent advances in mechanisms and management. Stresa,
      Italy, May 28-29, 1999. Proceedings.

PMID- 10970176
TI  - LICE (Italian League against epilepsy) National Congress in collaboration with
      the Italian Society of Clinical Neurophysiology. 23-26 June 1999, Roma, Italy.
      Abstracts.

PMID- 10970177
TI  - Re: "Naratriptan in the prophylaxis of transformed migraine" (Sheftell FD
      Rapoport AM, Coddon DR. Headache.1999,39:506-510).

PMID- 10970178
TI  - Purification and characterization of a histidine-binding protein from Salmonella
      typhimurium LT-2 and its relationship to the histidine permease system.

PMID- 10970179
TI  - On the mechanism of action of adrenocorticotropic hormone. The stimulation of
      thymidine kinase activity with altered properties and changed subcellular
      distribution.

PMID- 10970180
TI  - Glycoprortein biosynthesis in small intestinal mucosa. I. A study of
      glycosyltransferases in microsomal subfractions.

PMID- 10970181
TI  - 3-Phosphoglycerate phosphatase in plants. I. Isolation and characterization from
      sugarcane leaves.

PMID- 10970182
TI  - From herbal Prozac to Mark McGwire's tonic: how the Dietary Supplement Health and
      Education Act changed the regulatory landscape for health products.

PMID- 10970183
TI  - The Washington Hospital Center example: a hospital's guide to implementing the
      rapid organ recovery program.

PMID- 10970184
TI  - The Defense Threat Reduction Agency: a note on the United States' approach to the
      threat of chemical and biological warfare.

PMID- 10970185
TI  - The Texas Health Care Liability Act: Texas is the first state to listen to the
      concerns of its health care consumers, but how much has it heard?

PMID- 10970186
TI  - Incidence of germline hMLH1 and hMSH2 mutations (HNPCC patients) among newly
      diagnosed colorectal cancers in a Slovenian population.

PMID- 10970187
TI  - Does the survival motor neuron protein (SMN) interact with Bcl-2?

PMID- 10970188
TI  - Novel mutations in the homogentisate-1,2-dioxygenase gene identified in Slovak
      patients with alkaptonuria.

PMID- 10970189
TI  - Clinical and molecular correlates of somatic mosaicism in neurofibromatosis 2.

PMID- 10970190
TI  - Many deltaF508 heterozygote neonates with transient hypertrypsinaemia have a
      second, mild CFTR mutation.

PMID- 10970191
TI  - Further evidence for genetic heterogeneity of autosomal dominant disorders with
      accumulation of multiple deletions of mitochondrial DNA.

PMID- 10970193
TI  - Prenatal detection of trisomy for the entire long arm of chromosome 7.

PMID- 10970192
TI  - Liebenberg syndrome: brachydactyly with joint dysplasia (MIM 186550): a second
      family.

PMID- 10970194
TI  - Cockayne syndrome associated with low CSF 5-hydroxyindole acetic acid levels.

PMID- 10970195
TI  - Unilateral lobar pulmonary agenesis in sibs.

PMID- 10970196
TI  - From the Centers for Disease Control and Prevention. West Nile virus activity-
      New York and New Jersey, 2000.

PMID- 10970197
TI  - From the Centers for Disease Control and Prevention. Progress toward
      poliomyelitis eradication--European Region 1998-June 2000.

PMID- 10970198
TI  - From the Centers for Disease Control and Prevention. Update: Nucleic acid
      amplification tests for tuberculosis.

PMID- 10970199
TI  - JAMA patient page. Angina.

PMID- 10970200
TI  - [Technology and medicine].

PMID- 10970201
TI  - The beginning and expansion of flow cytometry in Brazil.

PMID- 10970202
TI  - Alzheimer's disease. Plaque removers and shakers.

PMID- 10970203
TI  - Brachial amyotrophic diplegia: a slowly progressive motor neuron disorder.

PMID- 10970204
TI  - Neurology and psychiatry: closing the great divide.

PMID- 10970205
TI  - In which journals will pediatricians find the best evidence for clinical
      practice?

PMID- 10970206
TI  - Cost-effectiveness/risk factors.

PMID- 10970207
TI  - The effects of blood transfusion protocol on retinopathy of prematurity.

PMID- 10970208
TI  - The effects of blood transfusion protocol on retinopathy of prematurity.

PMID- 10970209
TI  - Eradication of group A streptococci.

PMID- 10970210
TI  - Proceedings of the IV and V Scientific-Education Conference of Warsaw Division of
      the Polish Nephrological Society: Nephrological Days of Plock.

PMID- 10970211
TI  - Another plagiarised paper in Preglad Lekarski.

PMID- 10970212
TI  - [Serotypes of Salmonella isolated from the Lujan River, Argentina].
AB  - In this work, the serotypes of Salmonella genus polluting the waters of Lujan
      River, situated in the north east of the province of Buenos Aires, Argentina,
      were studied. A total of 690 samples of water were collected and analysed from
      February 1988 through December 1989, at three different sites. They were obtained
      according to the Moore technique and then preenriched in buffered peptone water
      and enriched in Rappaport-Vassiliadis Soya peptone broth was carried out. The
      isolations were realised in brilliant green-desoxycholate agar and bismuth
      sulphite agar and the presumptive colonies to be Salmonella were tested by the
      standard biochemical identification. Salmonella spp. was isolated in 434 samples
      (62.9%). The predominant serotype was S. Anatum, followed in a decreasing order
      by S. Montevideo, S. Newport and S. Bredeney. A large amount of serotypes that
      are isolated with very low frequency and very rarely in other hidric courses in
      the country were: S. Westhampton, S. Poona and S. Saintpaul were found.

PMID- 10970214
TI  - The position of moving objects.

PMID- 10970213
TI  - [Potassium transport in yeast].
AB  - K+ transport is vital for all cells. The first model to explain K+ transport in
      yeast was a redox potential driven H+/K+ antiporter. Later, a H+-ATPase was
      described which generates a H+ gradient, acid outside. This proton gradient is
      used by a secondary transporter, which transports K+ to the inside. These
      transporters are separate proteins, that have been isolated and their genes have
      been cloned. Furthermore, in Saccharomyces cerevisiae two different K+
      transporters have been described. K+ exit occurs through K+ channels and through
      H+/K+ antiporters that seem to anticipate in the regulation of internal pH. In
      addition, yeast produces a large amount of CO2 during the fermentation process.
      CO2 accumulation in turn results in the establishment of a Donnan potential due
      to the accumulation of bicarbonate, which retains large quantities of K+. In S.
      cerevisiae, bicarbonate is responsible for a large accumulation of K+. Also, the
      H+-ATPase, by pumping protons to the outside, favors the formation of bicarbonate
      which cannot diffuse to the extracellular environment leading to cytoplasmic pH
      values near 7.0. Bicarbonate accumulation allows yeast to maintain large pH
      gradients across the plasma membrane.

PMID- 10970215
TI  - The position of moving objects.

PMID- 10970216
TI  - Biotechnology. Perseverance leads to cloned pig in Japan.
AB  - Low success rates and unpredictable results have plagued cloning researchers,
      particularly those trying to clone pigs. Now, on page 1188, Japanese researchers
      offer the first scientific report of a cloned pig, named Xena, raising hopes that
      pigs could one day provide an unlimited supply of organs for transplantation
      thanks to their close physiological relationship to humans. But this week those
      hopes were dealt a blow by more evidence suggesting that pig retroviruses can
      infect human cells.

PMID- 10970217
TI  - Mars exploration. Plan for two rovers squeezes NASA budget.
AB  - NASA's decision last week to send two rovers to Mars in 2003 is being hailed by
      researchers as affirming the agency's commitment to exploring the Red Planet. But
      once the applause dies down, cash-strapped space science managers will be forced
      to make tough decisions about how to shoulder the added $200 million cost of a
      second mission, starting with $96 million that must come out of NASA's 2001
      budget.

PMID- 10970218
TI  - Tumor angiogenesis. Gene expression patterns identified.
AB  - Researchers have obtained the most detailed sketch yet of how cancerous tumors
      secure the blood supplies that nourish their growth. On page 1197, a team reports
      the results of a large-scale comparison of the genes expressed in the blood
      vessels of human colon cancers and of normal colon tissue. They've found that the
      gene expression patterns of the two types of vasculature are distinctly
      different. The findings could help researchers develop new anticancer drugs that
      work by homing in on the protein products of genes that are overexpressed in
      tumor vessels, thus shutting off the growth of blood vessels the tumor needs to
      survive.

PMID- 10970219
TI  - Marine conservation. Virginia gets crabby about harvest limits.

PMID- 10970220
TI  - Agriculture. Variety spices up Chinese rice yields.

PMID- 10970221
TI  - Microbiology. A weak link in TB bacterium is found.
AB  - The secret of the success of Mycobacterium tuberculosis, the pathogen that causes
      tuberculosis, is that it can linger undetected in the lungs for decades, hiding
      from the immune system's macrophages that aim to chew it up and spit it out. Now
      a team of researchers has uncovered a vulnerability in this resilient bug that
      suggests new ways to starve it out of its bolt-hole.

PMID- 10970222
TI  - Evolution 2000 meeting. Evolutionary trends from bacteria to birds.
AB  - Talks at Evolution 2000, held here in late June, covered the gamut of
      evolutionary biology, from life history changes in bacteria to the origins of
      modern bird diversity. Researchers reported on senescence in single-celled
      organisms and an origin for modern birds that is both farther back in time and
      farther south than generally believed.

PMID- 10970223
TI  - Reflections on a retraction.

PMID- 10970224
TI  - Ancient DNA: do it right or not at all.

PMID- 10970225
TI  - Search for the origin of HIV and AIDS.

PMID- 10970226
TI  - Retraction.

PMID- 10970227
TI  - Ethics. Protecting communities in biomedical research.
AB  - Although for the last 50 years, ethicists dealing with human experimentation have
      focused primarily on the need to protect individual research subjects and
      vulnerable groups, biomedical research, especially in genetics, now requires the
      establishment of standards for the protection of communities. We have developed
      such a strategy, based on five steps. (i) Identification of community
      characteristics relevant to the biomedical research setting, (ii) delineation of
      a typology of different types of communities using these characteristics, (iii)
      determination of the range of possible community protections, (iv) creation of
      connections between particular protections and one or more community
      characteristics necessary for its implementation, and (v) synthesis of community
      characteristics and possible protections to define protections appropriate for
      each type of community. Depending on the particular community, consent and
      consultation, consultation alone, or no added protections may be required for
      research.

PMID- 10970228
TI  - Neuroscience. More to seeing than meets the eye.
AB  - A single event may elicit several different sensory stimuli such as vision,
      sound, and touch. But how does the brain know which of the many different stimuli
      arriving in the sensory cortex of the brain are connected? In her Perspective, de
      Gelder discusses new findings showing that when a touch is applied on the same
      side of the body as a visual cue, vision is enhanced (Macaluso et al.). She
      explains that this effect is due to neurons projecting from the somatosensory
      (touch) area of the sensory cortex back to the visual cortex. These neurons keep
      the visual cortex informed about tactile stimuli elicited at the same time as the
      visual stimuli.

PMID- 10970229
TI  - Apoptosis. Mitochondria--the death signal integrators.
AB  - Many of the intricate pathways of apoptosis that instruct a cell to kill itself
      involve the convergence of key proteins on the membranes of mitochondria. Such
      proteins induce the permeabilization of mitochondrial membranes and the release
      of caspase enzymes and nuclease activators that set in motion the final stages of
      programmed cell death. Now, as Brenner and Kroemer discuss in their Perspective,
      a proapoptotic transcription factor called TR3 has been found to move from its
      normal location in the nucleus to the mitochondria and to promote release of
      cytochrome c, a key event in apoptosis (Li et al.)

PMID- 10970230
TI  - Genetics. L1 retrotransposons shape the mammalian genome.
AB  - What are all of those retrotransposons doing buzzing about in our genome?
      According to Kazazian, in his Perspective this week, these mobile pieces of DNA
      are busy reshaping our genome, making it more diverse and enabling us to survive
      and thrive through the vagaries of evolution. And just how do they do this?...zip
      to page 1152 to find out.

PMID- 10970231
TI  - Introductory note to: Fibrosis year 2000.

PMID- 10970232
TI  - What influences medical students' choice of surgical careers--a critical
      appraisal.

PMID- 10970233
TI  - [Epicutaneous tests in suspected adverse reactions to dental material].

PMID- 10970234
TI  - The optimal treatment for haemophiliacs who have developed factor VIII or -IX
      antibodies.

PMID- 10970235
TI  - Poliomyelitis or acute flaccid paralysis in future.

PMID- 10970236
TI  - National Institutes of Health Workshop on the Role of Dietary Supplements for
      Physically Active People. Bethesda, Maryland, USA. June 3-4, 1996. Proceedings.

PMID- 10970237
TI  - Plasmapheresis in the treatment of glomerulonephritis: indications and
      complications.

PMID- 10970238
TI  - High intraocular pressure and survival: the Framingham studies.

PMID- 10970239
TI  - Retinal detachment in myopic eyes after laser in situ keratomileusis.

PMID- 10970240
TI  - Retinal detachment in myopic eyes after laser in situ keratomileusis.

PMID- 10970241
TI  - Compression of the prechiasmatic optic nerve produces a junctional scotoma.

PMID- 10970242
TI  - Domestic violence and the trauma surgeon.
AB  - BACKGROUND: Domestic violence has become increasingly recognized as a public
      health problem, and was declared a national epidemic by C. Everett Koop in 1992.
      In the United States, 1 to million women yearly suffer injuries due to domestic
      violence, and 30% to 50% of female homicides are committed by a present or former
      partner. The majority of these murder victims had either been seen in emergency
      rooms for prior domestic violence-related injuries, or had reported these
      injuries to the police. It is estimated that 50% of all acute injuries and 21% of
      all injuries in women requiring urgent surgery ar the result of partner abuse.
      DATA SOURCE: Medline and current literature review. CONCLUSIONS: Health care
      professionals in the emergency room are an important contact with the victims of
      domestic violence, and timely identification and intervention can save lives.
      Overall, upwards of 35% of all emergency room visits by women are the result of
      domestic violence, whether due to acute injury, problems during pregnancy, or
      stress-related complaints. Unfortunately, domestic abuse is infrequently
      disclosed voluntarily by the patient, and often overlooked by the treating
      physician. Thus, the purpose of this review is to familiarize surgeons with the
      presentation and management of victims of this hidden epidemic.

PMID- 10970243
TI  - Stress in trainee anaesthetists.

PMID- 10970244
TI  - [Suspected sexual abuse in children].

PMID- 10970245
TI  - Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular
      cardiomyopathy linked to chromosome 10q.
AB  - Twenty-one members of a Swedish family suffering from myopathy and cardiomyopathy
      underwent neurological and cardiological investigations. Medical charts of 2
      affected deceased patients were reviewed. Twelve patients had myopathy. The
      distribution of weakness was axial in mildly affected, axial and predominantly
      distal in moderately affected, and generalized in severely affected patients. The
      electromyogram showed signs of myopathy in 10 patients. Muscle biopsy specimens
      showed myopathic changes, rimmed vacuoles, and accumulation of desmin,
      dystrophin, and other proteins. Electron microscopy revealed granulofilamentous
      changes and disorganization of myofibrils. Several patients had episodes of chest
      pain or palpitations. Three men had arrhythmogenic right ventribular
      cardiomyopathy. Nonsustained ventribular tachycardia, atrial flutter, and
      dilatation of the ventricles mainly affecting the right ventricle were
      documented. Two of them had a pacemaker implanted because of atrioventricular
      block and sick sinus syndrome. Inheritance is autosomal dominant with variable
      onset and severity of skeletal muscle and cardiac involvement. Linkage analysis
      of candidate chromosomal regions showed a maximum 2-point LOD score of 2.76 for
      marker locus D10S1752 on chromosome 10q. A multipoint peak LOD score of 3.06
      between markers D10S605 and D10S215 suggests linkage to chromosome 10q22.3, and
      this region may harbor a genetic defect for myofibrillar myopathy with
      arrhythmogenic right ventricular cardiomyopahty.

PMID- 10970246
TI  - Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion
      protein gene.
AB  - The clinical course, neuropathological features, and genetic findings in 3
      members of a German family carrying a novel 120-bp insertion in the prion protein
      (PrP) gene are described. Genetic analysis of the mutated allele revealed a
      sequence of five extra octapeptide repeats, distinct from those of the two
      previously reported families with an insertion of this size. There was
      distinctive variation in the clinical course and the onset and duration of the
      illness in the  documented subjects. Neuopathological evaluation showed neuronal
      loss and gliosis in the neocortex of the 3 examined cases; spongiform
      degeneration was found in 2 of them. PrP immunoreactivity of unusual morphology
      and distinct distribution was present in the cerebellem and neocortex ("blurred
      staining") of 2 examined cases. One subject showed features usually found in
      sporadic Creutzfeldt-Jacob disease with a punctate type of PrP deposition in the
      cerebellum. In addition, there were some plaque-like PrP aggregates
      morophologically similar to the other 2 cases in the molecular layer of the
      cerebellum, and unusual Prp immunoreactivity ("fleecy staining") was found in the
      neocortex. The clinicopathological heterogeneity in the documented family is in
      accordance with the phenotypic variability associated with previously reported
      insertions.

PMID- 10970247
TI  - Detection of 14-3-3 brain protein in the cerebrospinal fluid of patients with
      paraneoplastic neurological disorders.
AB  - The detection of 14-3-3 protein in cerebrospinal fluid by immunoblotting is
      useful for the diagnosis of Creutzfeldt-Jakob disease (CJD). We found 14-3-3
      protein in 10 of 80 (12.5%) patients with paraneoplastic neurological disorders
      (PNDs), whose presenting symptoms may mimic those of CJD. In 47 of 48 CJD
      patients, the 14-3-3 protein was detected as a single band, and it was detected
      as a double band in 1 patient. The double-band pattern was observed in 9 of 10 14
      3-3 protein-positive patients with PNDs. The 14-3-3 protein assay may be positive
      in PND patients, but the immunoblotting pattern distinguishes most PND samples
      from those of CJD.

PMID- 10970249
TI  - Association for the Study of Food and Society and Agriculture, Food and Human
      Values: joint annual meeting. 1-4 June 2000, New York, USA. Abstracts. .

PMID- 10970248
TI  - Novel Fosfomycin resistance of Pseudomonas aeruginosa clinical isolates recovered
      in Japan in 1996.

PMID- 10970250
TI  - Right turn.

PMID- 10970251
TI  - Diets: why don't they work?

PMID- 10970252
TI  - The effect of continuous quality improvement on compliance with clinical practice
      guidelines in an optometric clinic: a retrospective review.
AB  - BACKGROUND: Quantitative documentation of quality is becoming increasingly more
      important. The SUNY State College of Optometry established clinical protocols
      outlining clinical standards for patient care. We compared documentation of
      actual clinical performance to these standards. METHODS: The Primary Care
      Service's Quality Management Team retrospectively reviews a random 10% sample of
      charts of patients seen in the teaching clinic of the SUNY State College of
      Optometry on an ongoing basis. They compare the care documented in the medical
      record to internally distributed clinical protocols. We reviewed the resultant
      data from January 1995 through June 1997 by analyzing the number of indicators
      that were out of compliance for each month. Then we graphed these data to
      ascertain trends and variability to determine what effect this continuous quality
      improvement process had on clinical care as measured by compliance with clinical
      protocols. RESULTS: A least-squares regression analysis demonstrated a
      correlation (0.717) between the decreasing number of items out of compliance and
      the time during which feedback was provided (r2 = 0.5143, p = 0.0001). These data
      show a distinct downward trend, indicating better compliance with the clinical
      protocols over time. We also found that the variability of the data decreased
      during the time period studied. CONCLUSIONS: A properly designed continuous
      quality improvement program that gives appropriate feedback to faculty
      optometrists and student interns measurably increased their compliance with--and
      decreased their variability from--this clinic's internally distributed clinical
      protocols over a 30-month time period.

PMID- 10970253
TI  - Prescription safety eyewear: impact studies of lens and frame failure.
AB  - OBJECTIVES: To determine if a plano lens could be the test lens for all
      prescription (Rx) lenses and to investigate why Rx lenses pop out of safety
      eyewear. DESIGN: Plano and Rx polycarbonate lenses (n = 641) with varying
      thickness and edge geometry, mounted on steel lens holders, and Rx safety eyewear
      (n = 128) placed on headforms were impacted with test objects of varying diameter
      and hardness. Impacts were studied with 500 to 2,000 frames-per-second motion
      analysis. RESULTS: Plano lenses were at least, or more, prone to failure
      (dislodgment, perforation, shatter, or crack) than -3.00 or +3.00 lenses of the
      same minimum thickness. More than 40% of safety frames with removable lenses
      broke or had lenses pop out when impacted with energies expected in industry and
      sports. CONCLUSIONS: Plano lenses can be used as the test lenses for all Rx
      lenses made of the same material with the same minimal thickness. The ANSI Z87.1
      1989 industrial standard for Rx eyewear is inadequate for sports or other
      activities with high-impact potential. The best lens-retention system has, as a
      component, a frame with a bevel perpendicular to a frontal impact force.

PMID- 10970254
TI  - Implications of problem-based education for the future of optometric practice.
AB  - BACKGROUND: Optometry is changing from single-doctor, refraction-oriented
      practices toward group practices in which increasingly complex patient problems
      are managed. To prepare students for new modes of practice, the traditional
      lecture style of education is being supplemented with innovative techniques, such
      as problem-based learning (PBL). METHODS: Using PBL in a medical or optometric
      environment, a group of students would be given a complete case in the
      Subjective, Objective, Assessment, and Plan (SOAP) format. Then they would be
      asked to use the case as a basis for studying the underlying mechanism of the
      disease presented, the therapies available, why the management plan was selected,
      and why the patient responded as he or she did. RESULTS: Students work in groups
      to investigate the cases using on- and off-line resources. They set learning
      objectives for themselves and the group, and they evaluate each other's
      performances. A faculty member serves as a guide during this process.
      CONCLUSIONS: Students who complete a PBL course have not memorized a mountain of
      details as they would have in a traditional course, but have learned how to find
      and integrate information about patients, cases, diseases, etc. This enables them
      to deal with the exponential increase in knowledge that is occurring. In
      addition, by working together on PBL cases, students prepare themselves for group
      and other interactive practice environments.

PMID- 10970255
TI  - Afferent pupillary defect associated with optic nerve head drusen.
AB  - BACKGROUND: Optic nerve head drusen (ONHD) are a relatively uncommon finding with
      an estimated prevalence of anywhere from 0.3% to 2%. Reports of relative afferent
      pupillary defects (RAPDs) associated with ONHD are scarce. CASE REPORT: A patient
      with an RAPD was found to have ONHD as the only apparent etiology of the RAPD.
      The various diagnostic tests relevant to the case, the differential diagnosis,
      and the pathological features of ONHD are discussed. CONCLUSIONS: It is important
      for the clinician to consider an RAPD as a possible pathological feature of ONHD-
      especially with an asymmetric presentation.

PMID- 10970256
TI  - Legal responsibilities when fitting minors with contact lenses.
AB  - BACKGROUND: Practitioners must understand their legal responsibilities in fitting
      minors with contact lenses, which include informed consent, contractual
      obligations, and the Statute of Limitations. Minors are children and teenagers
      who have not yet reached voting age in their state--generally 18 years of age.
      Informed consent requires permission from the patient before a practitioner
      performs any treatment. For these young people, this consent generally can only
      be given by a parent or legal guardian. Minors can repudiate contracts made with
      them; therefore, the contractual obligation to pay for a contact lens fitting
      should be established with a parent or legal guardian. In most states, minors
      have additional time beyond the usual Statute of Limitations to bring a lawsuit.
      If practitioners recognize their legal responsibilities in caring for these
      special patients, fitting youngsters with contact lenses can be a rewarding part
      of practice.

PMID- 10970257
TI  - Are you Y2K-ready for low vision assistive technology?
AB  - The new Millennium brings a new breed of low vision assistive technology--some of
      it straight out of science fiction--and a surge in patients who can benefit from
      it.

PMID- 10970258
TI  - 5 steps to managing managed care.
AB  - A few simple steps can help eliminate many managed care payment problems before
      they occur.

PMID- 10970259
TI  - Lutein improves visual function in some patients with retinal degeneration: a
      pilot study via the Internet.
AB  - PURPOSE: The purpose of this article is to examine the effects of lutein
      supplementation on visual acuity, central visual-field area, and subjective
      visual disturbances in retinitis pigmentosa (RP) and related retinal
      degenerations, in an international study population recruited via an Internet
      mailing list. METHODS: Sixteen participants (13 with RP, three with other retinal
      degenerations) completed a 26-week program of lutein supplementation (40 mg/day
      for 9 weeks, 20 mg/day thereafter); 10 participants also took 500-mg
      docosahexaenoic acid (DHA)/day, vitamin B complex, and digestive enzymes. Ten
      participants previously taking vitamin A and/or beta-carotene continued those
      supplements throughout the study. Participants self-tested their visual acuity on
      their computer screen and their central visual-field extent on a wall chart,
      weekly for 14 weeks, bi-weekly thereafter. RESULTS: Mean visual acuity improved
      by 0.7 dB and mean visual-field area by 0.35 dB. Improvements started 2 to 4
      weeks after supplementation began, and plateaued at 6 to 14 weeks. Visual acuity
      gains were strongly correlated with eye color: 1.2 dB in seven blue-eyed
      participants, but 0.3 dB in seven dark-eyed participants. Participants who
      received previous supplements showed greater benefits in central visual-field
      area (0.55 dB) than those not receiving previous supplements (no change). No
      significant effects of age, sex, disease stage, or study supplement were found.
      CONCLUSIONS: Short-term vision improvements after lutein supplementation-
      previously reported in age-related macular degeneration--also occur in RP,
      especially in blue-eyed individuals; vitamin A may increase visual field
      benefits.

PMID- 10970260
TI  - Stargardt's macular dystrophy--a patient's perspective.
AB  - PURPOSE: The purpose of this paper was to evaluate life experience, including
      disease characteristics, daily-living activities, employment, interactions with
      health care professionals, and support services in patients diagnosed with
      Stargardt's macular dystrophy. METHODS: More than 200 patients with Stargardt's
      disease responded to a 68-question survey. Results were analyzed using SAS
      Statistical Analysis Package. RESULTS: Of 203 responders, 142 (70%) were women.
      Early disease onset occurred in more than 60% of patients. Blurred vision (134,
      66%) and glare (183, 90.1%) were the leading symptoms reported. Reading (116,
      57.1%), driving (86, 42.4%), and recognizing faces (66, 32.5%) were daily-living
      activities most difficult to perform. Patients with early disease onset had worse
      vision at presentation (p = 0.001), faster progression of visual loss (p =
      0.007), and were more often diagnosed with a non-physiological visual loss (p =
      0.007). Patients with late disease onset had more difficulty with orientation and
      coping skills (p = 0.02). Sixty-five percent of evaluated adults (108 of 165)
      were employed. CONCLUSIONS: Although the study illustrates that patients with
      Stargardt's disease can contribute and function well in contemporary society,
      issues related to depression, and availability and quality of health care, are
      still major concerns for this patient population. The study shows differences in
      progression of visual loss between patients, with early versus late disease onset
      indicating that age at onset and visual acuity at presentation might be two
      important factors influencing patient's visual prognosis. Finally, the study
      suggests parallels in psychological profiles between late age at onset
      Stargardt's disease and age-related macular degeneration patients.

PMID- 10970261
TI  - The Stickler syndrome: case reports and literature review.
AB  - BACKGROUND: Stickler syndrome is a progressive autosomal-dominant connective
      tissue disorder with numerous ocular and systemic manifestations. Ocular
      abnormalities include: retinal detachment, glaucoma, premature cataracts, high
      myopia, optically empty vitreous cavities, and retinal pigmentary changes.
      Systemic signs include premature osteoarthritis and hearing loss, as well as
      numerous skeletal and facial malformations, such as maxillofacial hypoplasia and
      cleft palate. While many affected patients are diagnosed as children who exhibit
      obvious skeletal abnormalities, diagnosis can be delayed due to variable
      expressivity. In some cases, systemic problems may be mild or nonexistent. Thus,
      Stickler syndrome should be considered in the differential diagnosis of any
      patient who manifests a strong family history of premature cataracts, glaucoma,
      or retinal detachment. CASE REPORTS: Three patients representing three different
      generations within the same family manifested severe ocular manifestations of
      Stickler syndrome, and minimal systemic involvement: a 56-year-old woman, her 25
      year-old son, and the first patient's 8-year-old grandson. CONCLUSIONS: Our cases
      highlight the need for appropriate vigilance in examining patients with a strong
      family history of common ocular disorders such as cataract, glaucoma, and retinal
      detachment. By recognizing the ocular and sometimes subtle systemic signs of
      Stickler syndrome, optometrists can play a vital role in limiting vision loss and
      improving the quality of life of affected patients and family members.

PMID- 10970262
TI  - Fixation dysfunction with intermittent saccadic intrusions managed by yoked
      prisms: a case report.
AB  - BACKGROUND: A 44-year-old woman came to us with a chief symptom of "jumping
      letters side-to-side, which is most noticeable while reading." The onset occurred
      after she had experienced a closed head traumatic brain injury 3 years earlier.
      Several neuro-ophthalmologists diagnosed a fixational instability secondary to
      saccadic intrusions and prescribed Gabapentin, which provided minimal relief.
      METHODS: The term saccadic intrusions refers to an inappropriate saccade with a
      disrupting effect on fixation. Our examination revealed a myopic anisometropia.
      Motility testing confirmed saccadic intrusions that lessened on occlusion of
      either eye and superior gaze. A plano spectacle with six-prism diopter-yoked base
      down was used to position the eyes in the superior null point. Electro
      oculography, using the Visagraph II, demonstrated pre and post changes with the
      prism. The uncorrected anisometropia allowed the patient to be monocular under
      binocular viewing conditions. CASE REPORT: The case report focuses on fixational
      problems that may occur secondary to traumatic brain injuries. There is evidence
      that the origin of the problem may be from uninhibited brain stem circuits.
      Pharmacological treatment may only offer transient improvement. The
      responsibility of a functional cure is often placed on the optometrist.
      CONCLUSION: This case demonstrates how an alternative use of prism and
      prescription application can play an important role in the management of fixation
      dysfunctions.

PMID- 10970263
TI  - Explosive growth.
AB  - Competing successfully against 19 superopticals, Gary Gerber, O.D. has built one
      of America's larger private optometry practices, proving the old business adage,
      'The Difference is Service.'

PMID- 10970264
TI  - Using break-even point to value a practice.

PMID- 10970265
TI  - Computing & technology.

PMID- 10970266
TI  - Malaria among seamen in Klaipeda during 1973-1998.
AB  - The number of people from Klaipeda and surroundings who before 1990 were employed
      in the shipping and fishing industry was about 10,000. At that time, from 3,000
      to 5,000 seafarers and fishermen travelled each year to malaria endemic countries
      of Africa, Asia and South America. Until 1973, malaria infections among seafarers
      in Lithuania occurred only sporadically, because ships based in Klaipeda very
      seldom sailed to ports in Africa. In the years 1973 - 1998, there were 113 cases
      of malaria registered in Klaipeda (P. falciparum 86, P. malarie 6, P.ovale 8, P.
      vivax 13). The diagnosis of 79 infections was confirmed by laboratory
      examinations in Klaipeda, and the remaining cases were confirmed by laboratory
      examination conducted in other places. Out of this number, there were 99
      infections of seafarers and fishermen, and 14 infections were recorded in
      soldiers returning from Afghanistan. In 1979 - 1987, there were 4 fatal cases of
      malaria reported: 3 seafarers died in Cameroon, Angola and Byelarussia, and one
      died in Klaipeda. At present, each year only about 500 seafarers travel to
      malarious areas in the tropics. There is no local transmission of malaria in
      Lithuania.

PMID- 10970267
TI  - New methods of seafarer's training: an internet "refresher course on first-aid
      and medical care on board".
AB  - Our objective is to facilitate seamen's health education, according to the
      recommendations of international organisations like IMO (STCW 1995) and EC
      (Directive 92/29): They recommend a refresher course on first-aid at least every
      5 years for persons in charge of medical care on board. In Spain the
      transposition of this Directive was published (RD 258/99). So, we thought that in
      order to help seafarers and officers in their training in prevention and in
      solving health problems derived from their occupational risks on board,
      continuing education could be implemented using an innovative and adaptable tool.
      No first-aid course can be useful without practical exercises. The term
      "refresher" (in this paper) is a way of reminding what people have learnt and
      practised in a previous practical course. In 1998, the Spanish Society of
      Maritime Medicine promoted a pilot internet refresher course for seafarers in its
      web, URL: "http://www.semm.org/curso/pauxm.html++ +". There are 10 didactic units
      (resources for medical assistance on board, radio-medical advice, environmental
      problems, travel medicine, cardio-respiratory resuscitation, prevention of
      problems in diving, death on board, occupational risk prevention ... etc.).
      Hypertext linked keywords help the student to revise the subject, a teacher can
      counsel him by e-mail and a multiple choice test, and clinical cases are included
      to check the comprehension of the didactic units. A CD and an English version of
      the course is being prepared.

PMID- 10970268
TI  - Concentration of microelements in blood and urine following intravenous chelation
      test in workers occupationally exposed to lead.
AB  - Microelements such as zinc, copper or magnesium play an important role in the
      regulation of metabolism on cellular level. The aim of the present work was to
      establish whether and to what extent the routine employment of diagnostic
      chelation test affects physiological concentration of microelements in blood and
      diurnal urine in workers occupationally exposed to lead. Based on the
      examinations carried out it has been found that intravenous administration of 1 g
      of Chelation essentially increases the urinary excretion of lead and zinc, thus
      lowering their content in blood.

PMID- 10970269
TI  - Occurrence of bacteria pathogenic to man in different types of diving
      apparatuses.

PMID- 10970270
TI  - The indigenous fisherman divers of Thailand: in-water recompression.
AB  - BACKGROUND: The Urak Lawoi, part of the Sea Gypsies of Thailand, have been diving
      using surface-supplied compressed air for more than 30 years. Their dive sites
      range from one hour to several days from their villages. Similar to other
      indigenous fisherman divers, the Urak Lawoi suffer from a high incidence of
      decompression illness. Their methods of in-water recompression were investigated.
      METHODS: In December 1998, available divers in two Urak Lawoi villages were asked
      if they had ever been treated using in-water recompression following
      decompression illness. If the divers responded positively, a questionnaire-based
      interview was carried out. Divers were asked to recall the cause of the accident,
      their diving patterns of the day, the parts of the body affected, the depths and
      times of in-water recompression and whether the problems were resolved as a
      direct result of this action. RESULTS: Eleven divers, aged 19-52, were
      interviewed. Causal factors listed by the divers included diving pattern 55%
      (6/11), rapid ascent 27% (3/11), and equipment failure 18% (2/11). Divers were
      recompressed in water using surface-supplied compressed air. The time between
      surfacing from the accident-related dive and being put back in the water ranged
      from immediately to 60 minutes. Depth and duration of in-water recompression
      ranged from 4 to 30 meters and 5 to 120 minutes. Outcomes reported by the divers
      were: improved or resolved at depth with no return of symptoms at surface in 64%
      (7/11), improved or resolved at depth with a return of symptoms at surface in 18
      (2/11), and not resolved at depth in 18% (2/11). DISCUSSION: Health-care workers
      in the villages may be able to provide basic first aid but, for some villages, a
      medical doctor may be as much as 10 hours away and a recompression facility as
      far as 16 hours in good weathier. In-water recompression has, within the diving
      population, proved to be an appropriate first-aid measure for decompression
      illness. A future project activity will develop consensus guidelines for
      determining under what circumstances in-water recompression using surface
      supplied air should be carried out and identify appropriate methods that the Urak
      Lawoi can apply.

PMID- 10970272
TI  - The manning industry in the Philippines and possible areas of improvement.

PMID- 10970271
TI  - Critical incident stress debriefing (CISD) in a shipping company.
AB  - Critical incident stress debriefing (CISD) is a method used successfully to
      reduce suffering from stress-related ailments such as insomnia, depression,
      anger, headaches etc. The resources of the shipping company are very limited and,
      thus, networking with existing organizations and specialists is necessary to
      carry out CISD effectively. The present company model has been adopted to take
      into account various situations and levels of disaster. The model has been
      adopted at three levels of events:Level 1. Serious accidents on shore, sudden
      deaths, severe events and threats. Events involving one or only few persons.
      Level 2. Life-threatening occupational accidents on board ship, suicide of a
      workmate, sudden death and fire on board ship. Events involving one person or
      limited group of persons. Level 3. Disasters at sea. Severe events involving all
      or nearly all persons on board ship. Actions at different levels: Level 1: A
      leaflet describing CISD, situations where it would be appropriate and where it is
      available, is given to each sailor. The victim is encouraged to seek CISD from
      public health care centres, most of which have their own services in Finland.
      Level 2. Training of about 8 hours is carried out by an experienced crisis
      psychologist for supervisors and officers on board ship. After the training they
      are able to identify stressful situations. At each harbour, the shipping company
      has made agreements with experienced crisis psychologists to act as specialists
      and contact persons on shore. These nominated psychologists will initiate CISD
      actions when necessary. If they need extra manpower they will turn to other
      psychologists. Level 3. In such serious accidents, the company's own resources
      alone are insufficient to provide effective CISD. All available public and
      private resources will he needed (health care organizations, Red Cross, Church
      etc.).

PMID- 10970273
TI  - The situation of maritime occupational health in Thailand.

PMID- 10970274
TI  - Maritime health and medical examinations for seagoing personnel in Indonesia.

PMID- 10970275
TI  - Health services for seafarers employed by the Indonesian State Oil Company
      "Pertamina".
AB  - In this article, the system of health services for seafarers employed by the
      lndonesian State Oil Company "Pertamina" is presented. The health services for
      Indonesian seafarers are provided by the port health authorities of the
      government in 22 large ports of the country, by the Indonesian Directorate of Sea
      Transportation, by the national shipowner company PELNI, and by the Indonesian
      Navy for their personnel, through their hospitals and clinics (reference to the
      article by T.H. Pangemanan and P. Margono, in the same issue of the International
      Maritime Health).

PMID- 10970276
TI  - The Latvian Maritime Medical Centre in Riga.

PMID- 10970277
TI  - Health care for seafarers in South Africa--an overview.

PMID- 10970278
TI  - The Institute of Maritime and Tropical Medicine in Gdynia, 1939-1999: 60 years of
      work.

PMID- 10970279
TI  - Polish maritime medicine in commemorative medals.

PMID- 10970280
TI  - First I.M.H.A. intercountry training course on maritime occupational health,
      Gdynia, 1999.

PMID- 10970281
TI  - Enzymatic kinetic resolution of piperidine atropisomers: synthesis of a key
      intermediate of the farnesyl protein transferase inhibitor, SCH66336.
AB  - The resolution of secondary amines via enzyme-catalyzed acylation is a relatively
      rare process. The kinetic resolution of a series of intermediates of SCH66336
      (1), by either enzymatic acylation of the pendant piperidine (4, 5) or hydrolysis
      of the corresponding carbamate 3, was investigated. In the case of 4, the
      molecule exists as a pair of enantiomers due to atropisomerism about the
      exocyclic double bond. The enzymatic acylation of (+/-)-4 was optimized in terms
      of acylating agent, solvent, and moisture content. The use of lipase, Toyobo LIP
      300, and trifluoroethyl isobutyrate as acylating agent resulted in
      isobutyrylation of the (+)-enantiomer, which is easily separated from the
      unwanted (-)-4. Hydrolysis of the isobutyramide 6c yielded the desired (+)-4 in
      high enantiomeric excess. (-)-4 may be recovered from the resolution step,
      racemized, and resubjected to enzymatic acylation to increase material
      throughput.

PMID- 10970282
TI  - An activated O --> N acyl transfer auxiliary: efficient amide-backbone
      substitution of hindered "difficult" peptides.
AB  - Overcoming the phenomenon known as "difficult" synthetic sequences has been a
      major goal in solid-phase peptide synthesis for over 30 years. In this work the
      advantages of amide backbone-substitution in the solid-phase synthesis of
      "difficult" peptides are augmented by developing an activated N(alpha)()-acyl
      transfer auxiliary. Apart from disrupting troublesome intermolecular hydrogen
      bonding networks, the primary function of the activated N(alpha)()-auxiliary was
      to facilitate clean and efficient acyl capture of large or beta-branched amino
      acids and improve acyl transfer yields to the secondary N(alpha)()-amine. We
      found o-hydroxyl-substituted nitrobenzyl (Hnb) groups were suitable N(alpha)()
      auxiliaries for this purpose. The relative acyl transfer efficiency of the Hnb
      auxiliary was superior to the 2-hydroxy-4-methoxybenzyl (Hmb) auxiliary with
      protected amino acids of varying size. Significantly, this difference in
      efficiency was more pronounced between more sterically demanding amino acids. The
      Hnb auxiliary is readily incorporated at the N(alpha)()-amine during SPPS by
      reductive alkylation of its corresponding benzaldehyde derivative and
      conveniently removed by mild photolysis at 366 nm. The usefulness of the Hnb
      auxiliary for the improvement of coupling efficiencies in the chain-assembly of
      difficult peptides was demonstrated by the efficient Hnb-assisted Fmoc solid
      phase synthesis of a known hindered difficult peptide sequence, STAT-91. This
      work suggests the Hnb auxiliary will significantly enhance our ability to
      synthesize difficult polypeptides and increases the applicability of amide
      backbone substitution.

PMID- 10970283
TI  - Convenient synthesis of 3,4-methano-1,2,3, 4-tetrahydroisoquinoline-3-carboxylic
      acid and its derivatives as doubly constrained nonproteinogenic amino acid
      derivatives.
AB  - Three strategies for the synthesis of the novel, doubly constrained, 3,4-methano
      1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives were
      evaluated. Only cyclocondensation of the mono(triphenyl)phosphonium salt derived
      from 1, 2-bis(bromomethyl)benzene with N-alkoxycarbonyloxamates in 1, 2
      dimethoxyethane in the presence of potassium carbonate and subsequent
      cyclopropanation with dimethylsulfoxonium methylide in dimethyl sulfoxide
      furnished suitable O- and N-protected derivatives of 3,4-methano-1,2,3,4
      tetrahydroisoquinoline-3-carboxylic acid in a convenient way. A detailed 2D DQF
      COSY and 2D NOESY NMR analysis of the rotational isomerism of the latter bicyclic
      amino acid derivatives was performed. Various O- and N-protection protocols were
      worked out to afford access to a whole range of new derivatives of the title
      amino acid, suitable for peptide synthesis.

PMID- 10970284
TI  - The first synthesis of the pentacyclic pyridoacridine marine alkaloids:
      arnoamines A and B.
AB  - The synthesis of the marine pyridoacridine alkaloids arnoamines A and B has been
      accomplished in six and seven steps from 4-chloro-8-methoxy-5-nitroquinoline in
      13% and 4% overall yield, respectively.

PMID- 10970285
TI  - Toward an understanding of the mechanisms of the intramolecular
AB  - The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of
      beta-silyloxy-gamma-pyrones bearing tethered alkenes has been characterized using
      ab initio methods. A comparative study for this sort of cycloaddition carried out
      at different computational levels points out that the B3LYP/6-31G calculations
      give similar barriers to those obtained with the MP3/6-31G level. Analysis of the
      energetic results shows that the reaction takes place along a stepwise process:
      first, the migration of the neighboring silyl group to the carbonyl group of the
      gamma-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which
      by a subsequent concerted intramolecular [5 + 2] cycloaddition affords the final
      cycloadduct. The cycloaddition process is very stereoselective due to the
      constraints imposed by the tether. The [5 + 2] cycloaddition reaction has a large
      barrier, and the presence of the silyloxy group and the intramolecular character
      of the process are necessary to ensure the thermodynamic and kinetic feasibility
      of these cycloadditions.

PMID- 10970286
TI  - Conformational design for 13alpha-steroids
AB  - The diastereomeric 16-bromo- and 16-azido-17-alcohols 5-8, 11, 12, 16, and 17 and
      17-ketones 3, 4, 9, and 10 of the 13alpha-estra-1,3, 5(10)-triene series were
      synthesized as precursors for biologically active compounds and chiral ligands
      for metal complexation. Conformational investigations of these and some other
      compounds via X-ray analysis and (1)H NMR spectroscopy show the existence of
      compounds with the classical steroid conformation (ring C chair, restricted
      conformation of ring D) and such with an atypical ring C twist-boat and a
      flexible ring D conformation. It could be shown that 17beta-substituents or
      flattening of the D-ring are responsible for the twist-boat conformation, whereas
      compounds containing a 17alpha-substituent or 17-keto group possess the classical
      conformation. By varying the substituents, compounds with either of these
      conformations can be intentionally synthesized. MO calculations confirmed the
      relative stability of the twist-boat conformation.

PMID- 10970287
TI  - Oxazolium-derived azomethine ylides. External oxazole activation and internal
      dipole trapping in the synthesis of an aziridinomitosene.
AB  - Intermolecular alkylation of the aziridinyl oxazole 20 using PhSO(2)CH(2)CH(2)OTf
      is possible despite the presence of potentially nucleophilic aziridine nitrogen.
      The resulting oxazolium salt 22 reacts with BnNMe(3)(+)CN(-) to produce the
      azomethine ylide 24b via electrocyclic ring opening of an oxazoline 23b. Internal
      cycloaddition affords 26 in 66% yield. After saponification and base-induced
      cleavage of the N-phenylsulfonylethyl group, conventional cyclization provides
      access to 33. Deprotection and DDQ oxidation completes the synthesis of the
      aziridinomitosene derivative 9b. The starting cis-disubstituted aziridine ester
      16 can be prepared by the aza-Darzens reaction of 15 with tert-butyl
      chloroacetate.

PMID- 10970288
TI  - A convenient method for the synthesis of DNA-recognizing polyamides in solution.
AB  - A convenient method for the synthesis of polyamides containing N-methylpyrrole
      (Py) and N-methylimidazole (Im) in solution has been developed. Most of the
      building blocks have been prepared by a haloform reaction in a simple way that
      column chromatography can be avoided. By use of the DCC/HOBT coupling reaction,
      the building blocks prepared have been effectively connected to construct a
      variety of subchains and polyamides without employing amino protection and
      deprotection. By use of the present method, an eight-ring polyamide,
      PyPyPyPygammaPyImImPybetaDp (gamma is gamma-aminobutyric acid, beta is beta
      alanine, Dp is N, N-dimethylpropyldiamine), has been synthesized by the coupling
      of two four-ring subchains in one step.

PMID- 10970289
TI  - Preparation, structure, and unique redox properties of mono-, bis-, and
      Tris(diarylmethylene)-1,3,5-trithianes and related compounds
AB  - A series of 1,3,5-trithianes 1-3 having diarylmethylene units were designed as
      novel electron donors giving highly colored cationic species upon oxidation. They
      were prepared along with the dithiane and dithiazine derivatives 4-6 by the
      reactions of lithiated heterocycles with diaryl ketones followed by dehydration.
      Voltammetric analyses indicate that a large structural change and/or transannular
      bonding are induced during their electrochemical oxidation. Mono(diarylmethylene)
      derivative 1a exhibits electrochromism with vivid change in color from faintly
      yellow to deep blue with concomitant rotation around the exocyclic bond. Both of
      the strongly colored salts obtained upon oxidation of 2,4-bis- and 2,4,6
      tris(diarylmethylene)-1,3,5-trithianes (2aa and 3) consist of the dications with
      a 1,2,4-trithiane ring, suggesting the easy skeletal rearrangement of the
      transannular dications with a trithiabicylo[3.1.0]hexane ring. Upon reduction of
      these salts were obtained bright yellow 12 and 13, respectively, with high
      electron-donating properties due to the tetraarylbutadiene-type conjugation, thus
      giving another class of electrochromic compounds.

PMID- 10970290
TI  - Conformational analysis in solution of C(2)-symmetric 1, 1'-binaphthyl
      derivatives by circular dichroism spectroscopy and cholesteric induction in
      nematic mesophases
AB  - The twisting ability of a series of 1,1'-binaphthalene compounds used as dopants
      in nematic solvents has been related to the dihedral angle theta between the two
      naphthalene moieties. While in the case of the more flexible compounds the sign
      and value of the helical twisting power is affected by several structural
      features that prevent a simple assignment of the conformation, in the presence of
      a covalent bridge that restricts the rotation around the C(1)-C(1') bond a
      reliable estimate of the conformational helicity could be obtained. This
      technique is complementary to CD spectroscopy that, for the investigated
      molecules, presents the same exciton patterns irrespective of the actual theta
      value.

PMID- 10970291
TI  - Oxidation of methyl trimethylsilyl ketene acetals to alpha-hydroxyesters with
      urea hydrogen peroxide catalyzed by methyltrioxorhenium
AB  - In the presence of catalytic amounts of MTO, methyltrioxorhenium, methyl
      trimethylsilyl ketene acetals are oxidized with urea hydrogen peroxide to afford
      alpha-hydroxy and alpha-siloxy esters. On treatment with potassium fluoride, the
      alpha-hydroxy esters are obtained in high yields.

PMID- 10970292
TI  - A new route to diastereomerically pure cyclopropanes utilizing stabilized
      phosphorus ylides and gamma-hydroxy enones derived from 1, 2-dioxines:
      mechanistic investigations and scope of reaction
AB  - A new chemical transformation for the construction of diversely functionalized
      cyclopropanes utilizing 1,2-dioxines and stabilized phosphorus ylides as the key
      precursors is presented. Through a series of mechanistic studies we have
      elucidated a clear understanding of the hitherto unknown complex relationship
      between 1, 2-dioxines 1a-e, and their isomeric cis/trans gamma-hydroxy enones (23
      and 21a-e), cis/trans hemiacetals 24a-e, and beta-ketoepoxides (e.g., 26), and
      how these precursors can be utilized to construct diversely functionalized
      cyclopropanes. Furthermore, several new synthetically useful routes to these
      structural isomers are presented. Key features of the cyclopropanation include
      the ylide acting as a mild base inducing the ring opening of the 1,2-dioxines to
      their isomeric cis gamma-hydroxy enones 23a-e, followed by Michael addition of
      the ylide to the cis gamma-hydroxy enones 23a-e and attachment of the
      electrophilic phosphorus pole of the ylide to the hydroxyl moiety, affording the
      intermediate 1-2lambda(5)-oxaphospholanes 4 and setting up the observed cis
      stereochemistry between H1 and H3. Cyclization of the resultant enolate (30a or
      30b), expulsion of triphenylphosphine oxide, and proton transfer from the
      reaction manifold affords the observed cyclopropanes in excellent diastereomeric
      excess. The utilization of Co(SALEN)(2) in a catalytic manner also allows for a
      dramatic acceleration of reaction rates when entering the reaction manifold from
      the 1,2-dioxines. While cyclopropanation is favored by the use of ester
      stabilized ylides, the use of keto- or aldo-stabilized ylides results in a
      preference for 1,4-dicarbonyl formation through a competing Kornblum-De La Mare
      rearrangement of the intermediate hemiacetals. This finding can be attributed to
      subtle differences in ylide basicity/nucleophilicity. In addition, the use of
      doubly substituted ester ylides allows for the incorporation of another
      stereogenic center within the side chain. Finally, our studies have revealed that
      the isomeric trans gamma-hydroxy enones and the beta-keto epoxides are not
      involved in the cyclopropanation process; however, they do represent an
      alternative entry point into this reaction manifold.

PMID- 10970293
TI  - Synthesis of 3,7-anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate as an IP(3)
      receptor ligand using a radical cyclization reaction with a vinylsilyl tether as
      the key step. Conformational restriction strategy using steric repulsion between
      adjacent bulky protecting groups on a pyranose ring
AB  - 3,7-Anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate (5) was designed as a
      novel IP(3)-receptor ligand having a C-glycosidic structure and was synthesized
      via a radical cyclization reaction with a temporary connecting vinylsilyl tether
      as the key step. The phenyl 2-O-dimethylvinylsilyl-3,4, 6-tri-O-benzyl-1-seleno
      beta-D-glucopyranoside (7), in the usual (4)C(1)-conformation, was successively
      treated with Bu(3)SnH/AIBN and under Tamao oxidation conditions to give a mixture
      of five C-glycosidic products. On the other hand, similar successive treatment of
      the corresponding 3,4-di-O-TBS-protected substrates 13 and 24, which were in an
      unusual (1)C(4)-conformaion due to the steric repulsion between the bulky silyl
      protecting groups, gave the desired 1alpha-C-glycosides 18 and 25, respectively,
      as the major products. Thus, the course of the radical cyclization was
      effectively controlled by a change in the conformation of the pyranose ring into
      a (1)C(4)-form due to steric repulsion between the adjacent bulky TBS-protecting
      groups at the 3- and 4-hydroxyl groups. From 25, the target 5 was synthesized via
      phosphorylation of the hydroxyls by the phosphoramidite method. The C-glycoside
      trisphosphate 5 has significant binding affinity for IP(3) receptor of calf
      cerebella.

PMID- 10970294
TI  - New and highly efficient synthesis of cis- and trans-opened Benzo[a]pyrene 7,8
      diol 9,10-epoxide adducts at the exocyclic N(2)-amino group of deoxyguanosine.
AB  - We describe a new and facile method for the synthesis of both cis- and trans
      opened N(2)-deoxyguanosine (dG) adducts of (+/-)-7alpha, 8beta-dihydoxy
      9beta,10beta-epoxy-7,8,9,10-tetra hydrobenzo[a]pyrene and (+/-)-7alpha,8beta
      dihydoxy-9alpha,10alpha -epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene at C-10. The
      key step in our approach is the direct coupling of O(6)-allyl-3', 5'-di-O-(tert
      butyldimethylsilyl)-2'-deoxyguanosine with these epoxides followed by the
      separation of the mixtures of cis- and trans-diastereomers produced. Overall
      coupling yields ranged from 45 to 65%. Stereochemistry of addition of the N(2)
      exocyclic amino group of dG (cis-trans, approximately 1:1) was assigned by NMR,
      and the absolute configuration of the dG adducts was unequivocally assigned by CD
      spectroscopy after separation of each individual diastereomer and cleavage of the
      allyl protecting group. A strong CD band at 279 nm in the O(6)-protected adduct
      was found to be diagnostic for configuration at C-10, with a negative band
      correlating with 10R configuration. The synthetic methodology described allows
      easy access to cis- and trans-opened N(2)-dG adducts which are valuable building
      blocks for the synthesis of adduct-containing oligonucleotides for physical and
      biochemical studies.

PMID- 10970295
TI  - Regeneration of PAPS for the enzymatic synthesis of sulfated oligosaccharides.
AB  - This paper describes the study of 3'-phosphoadenosine-5'-phosphosulfate (PAPS)
      regeneration from 3'-phosphoadenosine-5'-phosphate (PAP) for use in practical
      syntheses of carbohydrate sulfates which are catalyzed by sulfotransferases.
      Among the regeneration systems, the one with recombinant aryl sulfotransferase
      proved to be the most practical. This regeneration system was coupled with a
      sulfotransferase-catalyzed reaction, using a recombinant Nod factor
      sulfotransferase, for the synthesis of various oligosaccharide sulfates that were
      further glycosylated using glycosyltransferases.

PMID- 10970296
TI  - Stereodivergent approaches to the synthesis of isoxazolidine analogues of alpha
      amino acid nucleosides. Total synthesis of isoxazolidinyl deoxypolyoxin C and
      uracil polyoxin C.
AB  - The synthesis of new nucleoside analogues is currently of high interest. We
      report here full details of a study leading to the synthesis of novel
      isoxazolidinyl analogues of alpha-amino acid nucleosides. Three different
      synthetic approaches starting from L-serine have been evaluated for the
      construction of the isoxazolidine ring. These approaches consisted of Michael
      addition of N-benzylhydroxylamine to alpha,beta-unsaturated esters, nucleophilic
      addition of silyl ketene acetals to nitrones and 1, 3-dipolar cycloaddition of
      nitrones with vinyl acetate. Both Michael addition and nucleophilic addition of
      enolates could be carried out with stereocontrol at the newly formed stereogenic
      carbon. The stereocontrol observed in these reactions arises from the protecting
      group arrangement in the L-serine-derived substrates. Thus, whereas compounds
      having a diprotected nitrogen led to syn adducts, compounds having a
      monoprotected nitrogen gave rise to anti adducts. On the other hand, substrates
      having either a diprotected or monoprotected nitrogen atom led to anti adducts
      through the cycloaddition route. So, by choosing the appropriate route,
      isoxazolidinyl analogues having either syn or anti configuration with respect to
      the glycine unit can be prepared in enantiomerically pure form. The
      stereoselective synthesis of isoxazolidinyl analogues of deoxypolyoxin C and
      uracil polyoxin C in both D and L enantiomeric forms using these techniques has
      been achieved in good yields.

PMID- 10970297
TI  - The effect of polyamine homologation on the transport and cytotoxicity properties
      of polyamine-(DNA-intercalator) conjugates.
AB  - An efficient five-step synthetic method was developed to access a homologous
      series of spermidine-acridine and spermidine-anthracene conjugates. The
      derivatives were comprised of a spermidine fragment covalently tethered at its N4
      position to either an acridine or anthracene nucleus via an aliphatic chain
      (e.g., spermidine-[aliphatic tether]-acridine). The distance separating the
      spermidine and aromatic nucleus was altered by using different tethers comprised
      of four or five methylene units, respectively. These ligands (2-5) were shown to
      inhibit human DNA topoisomerase-II (TOPO-II) activity at 10 microM. Enzymatic
      activity was assessed as the ability to unknot (decatenate) and cleave
      kinetoplast DNA (kDNA). Polyamine conjugation did not disrupt the ability of the
      acridine-spermidine conjugates 2 and 3 to inhibit TOPO-II activity as compared
      with the 9-aminoacridine and 9-(N-butyl)aminoacridine controls (at 10 microM). In
      general, the acridine derivatives (2 and 3) showed higher TOPO-II inhibitory
      activity than their anthracene counterparts (4 and 5). However, this trend was
      reversed in a whole cell assay with L1210 (murine leukemia) cells, wherein the
      anthracene analogues were more potent than their acridine counterparts. In this
      regard the qualitative enzyme-based assay did not predict the trends in the
      corresponding IC(50) values. Within either series insertion of an additional
      methylene unit did not significantly alter activity. While the appended
      spermidine unit did not disrupt TOPO II inhibition by the tethered DNA
      intercalator, it did provide an alternative mode of entry into the cell as
      demonstrated by spermidine protection assays. These results were compared with a
      spermine-intercalator analogue. Of all the conjugates tested the N(4)-(4-(9
      aminoacridinyl)butyl)spermine hexahydrochloride (conjugate 16)resulted in the
      highest degree of L1210 cell rescue upon cotreatment of the cells with exogenous
      spermidine. It was concluded that the monoalkylated spermine motif present in 16
      holds promise as a better vector than its N4 monoalkylated spermidine
      counterpart.

PMID- 10970298
TI  - Alkyl- and arylthiodediazoniations of dry arenediazonium o-benzenedisulfonimides.
      Efficient and safe modifications of the stadler and ziegler reactions to prepare
      alkyl aryl and diaryl sulfides
AB  - The reaction between dry arenediazonium o-benzenedisulfonimides 1 and sodium
      thiolates in anhydrous methanol represents an efficient and safe procedure, of
      general validity, for the preparation of unfunctionalized or variously
      functionalized alkyl aryl and diaryl sulfides. As a rule, the reaction
      temperature was maintained at 0-5 degrees C for the alkylthiodediazoniations and
      at room temperature (20-25 degrees C) for the arylthiodediazoniations. The
      sulfide yields are generally high; of the 63 considered examples, 43 gave yields
      greater than 80% and 13 were between 70% and 80%. Lower yields were obtained only
      when sterically hindered diazonium salts or thiols were used. A good amount of
      the o-benzenedisulfonimide (8) was always recovered from the reactions and could
      be reused to prepare salts 1. The copious experimental data collected in
      homogeneous conditions have offered several starting points for the study of the
      mechanism of these reactions.

PMID- 10970299
TI  - Synthesis and characterization of the native anticodon domain of E. coli
      TRNA(Lys): simultaneous incorporation of modified nucleosides mnm(5)s(2)U, t(6)A,
      and pseudouridine using phosphoramidite chemistry.
AB  - The anticodon domain of E. coli tRNA(Lys) contains the hypermodified nucleosides
      mnm(5)s(2)U and t(6)A at positions 34 and 37, respectively, along with a more
      common psi at position 39. The combination of these three nucleotides represents
      one of the most extensively modified RNA domains in nature. 2-Cyanoethyl
      diisopropylphosphoramidites of the hypermodified nucleosides mnm(5)s(2)U and
      t(6)A were each synthesized with protecting groups suitable for automated RNA
      oligonucleotide synthesis. The 17 nucleotide anticodon stem-loop of E. coli
      tRNA(Lys) was then assembled from these synthons using phosphoramidite coupling
      chemistry. Coupling efficiencies for the two hypermodified nucleosides and for
      pseudouridine phosphoramidite were all greater than 98%. A mild deprotection
      scheme was developed to accommodate the highly functionalized RNA. High coupling
      yields, mild deprotection, and efficient HPLC purification allowed us to obtain
      1. 8 mg of purified RNA from a 1 micromol scale RNA synthesis. Our efficient
      synthetic protocol will allow for biophysical investigation of this rather unique
      tRNA species wherein nucleoside modification has been shown to play a role in
      codon-anticodon recognition, tRNA aminoacyl synthetase recognition, and
      programmed ribosomal frameshifting. The human analogue, tRNA(Lys,3), is the
      specific tRNA primer for HIV-1 reverse transcriptase and has a similar
      modification pattern.

PMID- 10970300
TI  - Zinc-mediated chain extension of beta-keto phosphonates
AB  - A variety of beta-keto phosphonates can be converted to gamma-keto phosphonates
      through reaction with ethyl(iodomethyl)zinc. The presence of alpha-alkyl
      substituents, Lewis basic functionality, and modestly acidic NH-protons are
      accommodated in substrates of this reaction. Chain extension of beta-keto
      phosphonates that contained olefinic functionality proceeded more quickly than
      cyclopropanation; however, it was not possible to effect the chain extension to
      the exclusion of cyclopropane formation. A primary reason for this imperfect
      chemoselectivity appears to be the slow chain extension of beta-keto
      phosphonates. Nevertheless, the simplicity, the scope, and efficiency of this
      method serve to make it an attractive alternative to the established methods for
      gamma-keto phosphonate formation.

PMID- 10970301
TI  - Asymmetric conjugate additions of chiral phosphonamide anions to alpha,beta
      unsaturated carbonyl compounds. A versatile method for vicinally substituted
      chirons
AB  - Reactions of anions derived from chiral nonracemic allyl, crotyl, and cinnamyl
      bicyclic C(2)-symmetrical phosphonamides with alpha, beta-unsaturated cyclic
      ketones, esters, lactones, and lactams take place at the gamma-position of the
      reagents. The products are diastereomerically pure or enriched beta-substituted
      carbonyl compounds. The method also provides easy access to vicinal substitution
      of as many as three stereogenic centers including in some cases quaternary carbon
      atoms, in a one-pot sequence.

PMID- 10970302
TI  - Synthesis of selectively labeled D-fructose and D-fructose phosphate analogues
      locked in the cyclic furanose form
AB  - 2,5-Anhydroglucitol and 2,5-anhydromannitol and their 6-phosphate and 1,6
      diphosphate derivatives are cyclic analogues of the alpha and beta anomers of D
      fructofuranose, D-fructofuranose-6-phosphate, and D-fructofuranose-1,6
      diphosphate. They were synthesized from protected D-mannose or D-glucose. The
      synthetic method was developed with emphasis on selective (2)H labeling of these
      compounds, as a model for (3)H incorporation, which will be used for further
      biochemical studies. A key cyclization step, based on a benzyl ether nucleophilic
      attack on an activated alcohol, constructed the ring system. The stereochemistry
      at C(2) (alpha/beta anomers) and at C(5) (D sugar) was controlled by selective
      epimerizations. Mono- and diphosphate analogues were obtained from the same
      intermediate by changing the sequence of deprotection and phosphorylation steps.

PMID- 10970303
TI  - One-step synthesis of biotinyl photoprobes from unprotected carbohydrates
AB  - A simple and versatile approach for the preparation of carbohydrate photoprobes
      has been developed. By a single-step reaction at 37 degrees C, a biotinylated
      carbene-generating unit was introduced to the reducing end of unprotected
      carbohydrates. Micromole quantities of N-acetyllactosamine, Lewis X
      trisaccharide, and sialyl Lewis X tetrasaccharide were easily converted to their
      biotinylated photoreactive analogues, which enabled the nonradioisotopic
      chemiluminescent detection of the photolabeled products. Thus, a sequence of
      lectin photoaffinity labeling, from the probe synthesis to the detection of
      labeled protein, was readily accomplished within one week. Our strategy may be
      applicable to any aldehyde-bearing ligand.

PMID- 10970304
TI  - Hydrogen-atom Abstraction/Cyclization in synthesis. Direct syntheses of coumestan
      and coumestrol
AB  - The synthesis of coumestrol has been achieved in five steps from 1, 3
      dimethoxybenzene. The key step is a photochemical cyclization of a glyoxylate
      ester.

PMID- 10970305
TI  - 6-s-cis locked analogues of the steroid hormone 1alpha, 25-dihydroxyvitamin D(3).
      Synthesis Of novel A-ring stereoisomeric 1, 25-dihydroxy-3-epi-19-nor-previtamin
      D(3) derivatives.
AB  - Efficient syntheses of A-ring synthons 24 and 32 are described from hydroxy ester
      16, which is easily available on a preparative scale from (-)-quinic acid. Key
      features of the syntheses were (a) the ability to selectively perform
      desilylations in the presence of p-nitrobenzoate esters and (b) the excellent
      yield and complete stereospecificity with which the configuration of alcohols 16,
      18, and 26 could be inverted under Mitsunobu conditions. Thus, A-ring synthons 24
      and 32 were both prepared in 35-38% yield (eight steps) from the common precursor
      16. The coupling of A-ring synthons 24 and 32 with the appropriate CD-ring/side
      chain fragment 7 provides access to novel 6-s-cis locked analogues of steroid
      hormone 1alpha, 25-dihydroxyvitamin D(3): 1alpha, 25-dihydroxy-3-epi-19-nor
      previtamin D(3) (37) and 1beta, 25-dihydroxy-3-epi-19-nor-previtamin D(3) (38),
      which are unable to undergo rearrangement to the respective vitamin D form by
      virtue of the absence of the C-19 methyl group. Compounds 37 and 38 can be used
      as tools for studying the genomic and nongenomic mechanisms of action of the
      previtamin form of the hormone 1alpha, 25-dihydroxyvitamin D(3).

PMID- 10970306
TI  - Mechanistic evaluation of the halocyclization of 4-penten-1-ol by some Bis(2
      substituted pyridine) and Bis(2,6-disubstituted pyridine)bromonium triflates
AB  - The halocyclization reaction of 4-penten-1-ol mediated by various bis(2
      substituted pyridine) and (2,6- disubstituted pyridine)bromonium triflates
      (P(2)Br(+)OTf(-)) was investigated to determine the influence of the substituents
      on the mechanism of reaction. In all cases, the reaction proceeds via a two-step
      process where the starting P(2)Br(+) reversibly dissociates to a reactive
      monosubstituted PBr(+), which then is captured by 4-penten-1-ol to form
      halocyclized product (2-bromomethyltetrahydrofuran). The dissociation rate
      constant of P(2)Br(+) (k(d)) is sensitive to the steric bulk at the 2- and 6
      positions, and in the case of the 2, 6-dicyclohexylpyridine or 2,6
      dicyclopentylpyridine, the P(2)Br(+) species are too unstable to isolate. The
      partitioning ratio of the reactive intermediate (PBr(+)) between reversal and
      product formation (k(-)(d)/k(2)) is not particularly sensitive to the nature of
      the pyridine, the limiting values being 3-7 except in the case of bis(2(-)
      menthylpyridine)bromonium triflate where the k(-)(d)/k(2) ratio is approximately
      80. The reaction of 4-penten-1-ol and its OD isotopomer with
      bis(lutidine)bromonium triflate was investigated to determine the deuterium
      kinetic isotope effect (dkie) on the bromocyclization reaction. The (k(
      )(d)/k(2))(H/D) ratio is 1.0, indicating that the rate-limiting step for the
      bromocyclization is probably formation of a PBr(+)-4-penten-1-ol complex which
      does not involve substantial changes in the bonding of the OH. The cyclization of
      4-penten-1-ol and 4-pentenoic acid mediated by bis(2(-)-menthylpyridine)bromonium
      triflate produces an enantiomeric excess in the cyclized products of only 2.4%
      and 4.8% respectively.

PMID- 10970307
TI  - Effect of acyl substituents on the reaction mechanism for aminolyses of 4
      nitrophenyl X-substituted benzoates
AB  - Second-order rate constants (k(N)) have been measured spectrophotometrically for
      the reaction of 4-nitrophenyl X-substituted benzoates with a series of alicyclic
      secondary amines in H(2)O containing 20 mol % dimethyl sulfoxide at 25.0 degrees
      C. The magnitude of the k(N) values increases with increasing the basicity of
      amines and with increasing the electron-withdrawing ability of the acyl
      substituent X. The Hammett plots obtained are not linear but show a break or
      curvature as the acyl substituent X becomes electron withdrawing for all the
      amines studied, while the Bronsted-type plots are linear with large beta(nuc)
      values for all the substrates investigated. The nonlinear Hammett plots suggest a
      change in the rate-determining step upon changing the acyl substituent X, whereas
      the linear Bronsted-type plots indicate that the rate-determining step does not
      change upon changing amine basicity. The Yukawa-Tsuno plots obtained are also
      linear with positive rho(X) and large r values, suggesting that the nonlinear
      Hammett plots are not due to a change in the rate-determining step upon changing
      the acyl substituent X, but due to resonance demand of the pi-electron donor
      substituent on the acyl moiety. The magnitude of the rho(X) and beta(nuc) values
      increases with increasing the basicity of amines and with increasing the electron
      withdrawing ability of the acyl substituent X, respectively, while that of the r
      values decreases with increasing rho(X) values and amine basicity.

PMID- 10970308
TI  - Steric influence of E- or Z-monosubstituted and terminally disubstituted vinyl
      groups in matrix-isolated cyclopentane-1,3-diyl triplet diradicals as probed by
      the zero-field EPR D parameter
AB  - The zero-field D parameter of the localized E, Z, and disubstituted vinyl
      cyclopentane-1,3-diyl triplet diradicals V was determined at 77 K in a 2
      methyltetrahydrofuran (2-MTHF) matrix. Good linear correlations were obtained
      with the semiempirically (PM3; r(2) = 0. 991, n = 19) and DFT (B3LYP; r(2) =
      0.998, n = 7) calculated spin densities of the triplet diradicals. The D values
      for the disubstituted triplet diradicals V are generally larger than the
      corresponding monosubstituted ones and, thus, the former are less well
      delocalized and thereby more poorly stabilized. For the E- and Z-diastereomeric
      pairs V, only marginal changes in the theoretical assessed spin densities as well
      as in the D values have been found. Steric effects operate and distort the
      conformation of the vinyl substituent in the triplet diradical V. This is
      adequately reproduced by theoretical calculations. For the diphenyl-substituted
      triplet diradical Vl, for example, they show a more or less planar alignment of
      the E-phenyl group and the allylic pi system (torsion angle 12 degrees ) and thus
      optimal delocalization of spin, whereas the Z-phenyl group is twisted about 78
      degrees out of plane and therefore is not involved in the delocalization and
      stabilization of spin. This results in a slightly higher D value (0.0368 cm(
      )(1)), and the spin is delocalized less than in the monosubstituted E-Vm one
      (0.0357 cm(-)(1)).

PMID- 10970310
TI  - Amination of Bis(trimethylsilyl)-1,2-bisketene with secondary amines: formation
      of aminodihydrofuranones
AB  - The bisketene (Me(3)SiC=C=O)(2) (3) reacts rapidly with 1 equiv of secondary
      amines to form aminodihydrofuranones 11 as the only observable products. This is
      in contrast to previous studies (J. Org. Chem. 1999, 64, 4690) of the reactions
      of 3 with primary amines in which 3 with 1 equiv of amine gives ketenyl amides 4,
      which slowly cyclize to succinimides 7. The kinetics of the reaction of 3 with
      morpholine obeyed a rate law with the term [morpholine](2), consistent with rate
      limiting formation of the enol amide 14 with catalysis by a second amine
      molecule. The subsequent formation of 11 is attributed to hindrance of
      ketonization of intermediate enol amides 14. The furanones 11 react with
      Me(3)SiOTf to form silyloxyfurans 16, and these react with diethyl
      diazodicarboxylate, forming maleamide derivatives 17.

PMID- 10970309
TI  - Vinyl and alkynyl pyrimidines as michael acceptors: an approach to a
      cylindrospermopsin substructure.
AB  - Vinyl pyrimidine 9 and alkynyl pyrimidine 24 undergo base-mediated intramolecular
      conjugate addition reactions in which a carbamate and a urea, respectively,
      behave as nitrogen nucleophiles. The cyclic carbamate derived from 9 was
      converted to 11 via a metalation-oxidation reaction in which 2-phenylsulfonyl-3
      phenyloxaziridine behaves as a hydroxylation reagent. The cyclic urea derived
      from 24 was converted to cylindrospermopsin substructure 30 using
      dimethyldioxirane to introduce the C(7) hydroxyl group.

PMID- 10970311
TI  - Selective synthesis of novel cyclic phenylazomethine trimers
AB  - Novel cyclic phenylazomethine trimers (CPAs) were synthesized in a one-step
      dehydration of the 4-aminobenzophenone derivatives in the presence of TiCl(4) or
      p-toluenesulfonic acid (PTS). The CPAs were isolated in over 90% yield under
      nondilute conditions. When using TiCl(4) as the dehydration agent, the induction
      of bulky substituents at the alpha-position of the substrate enhanced the yields
      of the CPAs. On the other hand, PTS served as an effective catalyst for the
      synthesis of the phenyl-substituted CPA. This different reactivity between
      TiCl(4) and PTS depends on the dehydration mechanism being dominated by a kinetic
      process or thermodynamic one. The obtained CPAs were confirmed by NMR, UV-vis
      spectra, and MM2 calculation to have only a Z conformation and a nonconjugated
      structure compared to the linear oligophenylazomethines (OPAs) and the aniline
      capped OPAs (OPA's).

PMID- 10970312
TI  - Cyclohexadienone diazeniumdiolates from nitric oxide addition to phenolates.
AB  - Sterically hindered phenols react with nitric oxide under basic condititons to
      give either cyclohexadienone diazeniumdiolates or oximates. Phenols with 2,6-di
      tert-butyl and 4-methyl (butylated hydroxy toluene, BHT), 4-ethyl, or 4-methoxy
      methylene substituents yield the corresponding 2,6-di-tert-butyl-2, 5
      cyclohexadienone-4-alkyl-4-diazeniumdiolate salts (4-methyl 1a, 4-ethyl 3a, 4
      methoxymethylene 5a). Phenols with 2,6-di-tert-butyl and 4-methylene (2,6-di-tert
      butylphenol) substituents yield 4-methoxymethylenediazeniumdiolate (5a) together
      with 2, 6-di-tert-butyl benzoquinone oximate (6a), while phenols with 2, 6-di
      tert-butyl and 4-methylenedimethylamino or hydrogen substituents yield
      exclusively 2,6-di-tert-butyl benzoquinone oximate (6a). Alkylation of the silver
      salts of 1a, or treating the O(2)-protonated diazeniumdiolate with diazomethane,
      both yield mixtures of O(1)- and O(2)-methylated isomers. All the compounds
      exhibit exothermic thermal decomposition except the quinuclidinium (1e, 3e, 5e)
      and triethylenediammonium (1f) salts which decompose endothermically. Three of
      the compounds namely "O(2)-protonated" (Z)-1-[4-(2, 6-di-tert-butyl-4-methyl
      cyclohexadienonyl)]diazen-1-ium+ ++-1, 2-diolinic acid (1b), O(2)-methyl (Z)-1-[4
      (2, 6-di-tert-butyl-4-methyl-cyclohexadienonyl)]diazen-1-ium+ ++-1,2-diolate
      (1c), and "O(2)-protonated" (Z)-1-[4-(2, 6-di-tert-butyl-4
      methoxymethylenecyclohexadienonyl)]diazen- 1-ium-1, 2-diolinic acid (5b) were
      characterized by single-crystal X-ray diffraction studies. The diazeniumdiolate
      framework in all the structures is coplanar with considerable pi-bonding
      delocalized over the O-N-N-O framework.

PMID- 10970314
TI  - New generation of organosilyl radicals by photochemically induced homolytic
      cleavage of silicon-boron bonds
AB  - Unlike bis(diethylamino)organosilylboranes,
      bis(diisopropylamino)organosilylboranes, which have UV absorption at longer
      wavelength than 300 nm, undergo photolysis to afford pairs of an organosilyl
      radical and a bis(diisopropylamino)boryl radical by homolytic scission of the
      silicon-boron bonds. Generation of organosilyl radical and organoboryl radical
      was confirmed by trapping experiments using TEMPO (2,2,6,6-tetramethylpiperidine
      N-oxyl). The organosilyl radical thus generated induces not only silylation of
      mono-olefins and silylative cyclization of dienes but also polymerization to
      afford polymers bearing organosilyl termini. On the other hand, the
      bis(diisopropylamino)boryl radical generated is not incorporated into the olefin
      adducts.

PMID- 10970313
TI  - Asymmetric syntheses of (-)-8-epi-swainsonine triacetate and (+)-1, 2-Di-epi
      swainsonine. Carbonyl addition thwarted by an unprecedented aza-pinacol
      rearrangement.
AB  - Indolizidines (-)-8-epi-swainsonine triacetate and (+)-1, 2-di-epi-swainsonine
      were synthesized from the O'Donnell Schiff base ester 1 derived from D-serine.
      Reductive-alkenylation of 1 with (i)()Bu(5)Al(2)H/H(2)C=CHMgBr followed by
      substrate-directed dihydroxylation of the pendant allylic group with OsO(4),
      reduction of imine, and cyclization with Ph(3)P/CCl(4) gave the polyhydroxylated
      pyrrolidines 8a and 8b as advanced intermediates. Efficient protecting group
      manipulations converted pyrrolidines 8a and 8b to their corresponding partially
      protected analogues 10a and 10b, which upon Swern oxidation and
      diastereoselective Keck-type allylation with BF(3).Et(2)O afforded the required
      three-carbon homologues (10a, >20:1 de; 10b, 3.5:1 de). Use of the chelating
      Lewis acid MgBr(2) instead of BF(3).Et(2)O with 10a led to a novel aza-pinacol
      rearrangement and allylation at the alpha-carbon to yield amino alcohol 17, which
      is similar to a hydride migration in the biosynthetic pathway of indolizidine
      alkaloids. Subsequent hydroboration, cyclization, and deprotection furnished (-)
      8-epi-swainsonine triacetate 15a and (+)-1,2-di-epi-swainsonine 16b in good
      overall yields (6.3% for 1 --> 15a, 13 steps, and 4.0% for 1 --> 16b, 14 steps).

PMID- 10970315
TI  - Ferromagnetic spin alignment in head-to-tail coupled oligo(1, 4
      phenyleneethynylene)s and Oligo(1,4-phenylenevinylene)s bearing pendant p
      phenylenediamine radical cations
AB  - The intramolecular and long-range ferromagnetic coupling between p
      phenylenediamine radical cations in head-to-tail coupled oligo(1, 4
      phenyleneethynylene)s and oligo(1,4-phenylenvinylene)s between neighbors and next
      nearest neighbors is described. UV/vis/near-IR experiments show that the radical
      cations are localized in the pendant p-phenylenediamine units of the conjugated
      oligomers. The ESR spectra of these oligo(1,4-phenyleneethynylene) and oligo(1, 4
      phenylenvinylene) di(radical cation)s are consistent with those of a triplet
      state. A linear behavior is observed for the doubly integrated ESR intensity of
      the DeltaM(s) = +/-1 and DeltaM(s) = +/-2 signals with the inverse temperature (I
      approximately 1/T), consistent with Curie's law. This behavior indicates a
      triplet ground-state diradical with a large triplet-singlet energy gap or
      possibly a degeneracy of singlet and triplet states.

PMID- 10970316
TI  - Ab initio computational studies of conformationally restricted cope
      rearrangements. First examples of fully concerted allenyl cope rearrangements
AB  - Results of (8,8)CASPT2/6-31G//(8,8)CASSCF/6-31G level calculations on the
      potential surface for the conformationally restricted allenyl Cope rearrangements
      of syn-5-propadienylbicylco[2.1.0]pent-2-ene (14) and syn-6
      propadienylbicyclo[2.1.1]hex-2-ene (15) are reported. Both are found to proceed
      through concerted pathways. Also included are the results of (6,6)CASPT2/6
      31G//(6,6)CASSCF/6-31G level calculations on the Cope rearrangements of syn-5
      ethenylbicyclo[2.1. 0]pent-2-ene (18), syn-6-ethenylbicyclo[2.1.1]hex-2-ene (19),
      and syn-7-vinylnorborene (20), which are found to involve diallylic diradical
      intermediates 26, 30, and 36, respectively. Previous studies have shown that the
      allenyl Cope rearrangement of 1,2, 6-heptatriene (1) to 3-methylene-1,5-hexadiene
      (2) involves a single transition structure that either proceeds to the
      monoallylic cyclohexane-1,4-diyl derivative 3 or bypasses 3 to form 2 directly.
      (4) More recently, the conformationally restricted allenyl Cope rearrangement of
      syn-7-allenylnorbornene (7) has also been found to involve tricyclic monoallylic
      cyclohexane-1,4-diyl intermediate 11. (7) The rearrangements of 14 and 15 appear
      to represent the first reported examples of fully concerted allenyl Cope
      rearrangements. Concertedness in these cases is ascribed to two parallel factors:
      (1) the relative instability of possible tricyclic diradical intermediates 16 and
      17, compared to diradical intermediates 3 and 11 formed in the rearrangements of
      1 and 7, respectively; and (2) the opportunity that exists to form sp-sp(2) sigma
      bonds in transition structures 21 and 23 that lead, respectively, to products 22
      and 24. By contrast, only weaker sp(2)-sp(2) sigma bonds could form in unobserved
      concerted transition structures leading to products 28 and 32, formed in the
      nonconcerted rearrangements of 18 and 19.

PMID- 10970317
TI  - Donor/Acceptor fulleropyrrolidine triads
AB  - New C(60)-based triads, constituted by a fulleropyrrolidine moiety and two
      different electroactive units [donor 1-donor 2 (10, 15a,b), or donor 1-acceptor
      (17, 21)], have been synthesized by 1,3-dipolar cycloaddition reaction of
      azomethyne ylides to C(60) and further acylation reaction on the pyrrolidine
      nitrogen. The electrochemical study reveals some electronic interaction between
      the redox-active chromophores. Triads bearing tetrathiafulvalene (TTF) and
      ferrocene (Fc) (10) or pi-extended TTFs and Fc (15a,b) show reduction potentials
      for the C(60) moiety which are cathodically shifted in comparison to the parent
      C(60). In contrast, triads endowed with Fc and anthraquinone (AQ) (17) or Fc and
      tetracyanoanthraquinodimethane (TCAQ) (21) present reduction potentials for the
      C(60) moiety similar to C(60). Fluorescence experiments and time-resolved
      transient absorption spectroscopy reveal intramolecular electron transfer (ET)
      processes from the stronger electron donor (i.e., TTF or extended TTF) to the
      fullerene singlet excited state, rather than from the poorer ferrocene donor in
      10, 15a,b. No evidence for a subsequent ET from ferrocene to TTF(*)(+) or pi
      extended TTF(*)(+) was observed.

PMID- 10970318
TI  - Kinetic studies on the thermal cis-trans isomerization of 1, 3-diphenyltriazene
      in aqueous solution. Effects Of acids and bases
AB  - The thermal cis-to-trans isomerization of 1,3-diphenyltriazene (DPT) has been
      investigated in buffered aqueous solutions by means of laser-flash photolysis
      techniques. The cis-to-trans isomerization process is found to be catalyzed by
      general acids and general bases as a result of acid/base-promoted 1,3-prototropic
      rearrangements. Acid catalysis is attributed to rate-limiting proton transfer to
      the nitrogen-nitrogen double bond of cis-DPT, whereas base catalysis is
      attributed to rate-limiting base-promoted ionization of the amino nitrogen of cis
      DPT leading to the isomerization. In addition, a process ascribed to the
      interconversion of cis rotamers through hindered rotation around the nitrogen
      nitrogen single bond is also observed; at high pH this process becomes rate
      limiting.

PMID- 10970320
TI  - N- vs O-protonation and the transannular substituent interaction in 8
      (Dimethylamino)-1-acetonaphthone
AB  - Dynamic NMR measurements of 8-(dimethylamino)-1-acetonaphthone 1 in neutral
      solutions reveal a solvent dependency of the barrier to NMe group interchange
      similar to that reported for N,N-dimethylacetamide. Titrating 1 with TFA in
      solvents of varying donicities gives rise to equilibrium mixtures of N-protonated
      aminoketone 2 and the O-protonated transannular addition product 3, the
      interconversion rate of which is slow on the NMR time scale at ambient
      temperature. The preference for O- or N-protonation is medium-dependent, the
      amount of N-protonated 2 increasing with a decrease in the nucleophilicity of the
      solvent. The set of equilibria which govern the interconversion of 2 and 3 in the
      titration mixtures are identified and their equilibrium constants evaluated from
      the NMR data. X-ray analysis of the crystalline trifluoroacetate salt of O
      protonated 3 indicates that the transannular N.CO bond of 3 is formed to an
      extent of only 80%. The equilibrium distribution of 2 and 3, paired with the
      tetrafluoroborate anion, depends on both the nucleophilicity and the polarity of
      the solvent. In PhNO(2) the enthalpy change 3 --> 2 amounts to 2.6 kcal/mol.

PMID- 10970319
TI  - Reaction of nitric oxide at the beta-carbon of enamines. A new method of
      preparing compounds containing the diazeniumdiolate functional group.
AB  - The reaction of nitric oxide (NO) with enamines has been investigated. Unlike
      previously reported reactions of NO as a free radical with alkenes, the
      electrophilic addition of NO to the beta-carbon of enamines results in the
      formation of compounds containing the diazeniumdiolate functional group (
      [N(O)NO](-)). This reaction between NO and enamines has been shown to be quite
      general and a variety of enamine-derived diazeniumdiolates have been isolated and
      characterized. While enamines derived from aldehydes and ketones whose structures
      allow for sequential multiple electrophilic additions tended to undergo
      overreaction leading to unstable products, it has been shown that this
      complication may be overcome by suitable choice of reaction solvent. The products
      obtained may exist as zwitterionic iminium salts or as neutral species depending
      upon the structure of the parent enamine. The diazeniumdiolate derived from 1-(N
      morpholino)cyclohexene is unique among the new compounds in that it spontaneously
      releases NO upon dissolution in buffered aqueous solution at pH 7.4 and 37
      degrees C. While the total quantity of NO released by this material (ca. 7% of
      the theoretical 2 moles) is apparently limited by a competing reaction in which
      it hydrolyzes to an alpha-diazeniumdiolated carbonyl compound and the parent
      amine, this feature may prove to be of great value in the development of
      multiaction pharmaceuticals based upon this new type of NO-releasing compound.
      Reports of enzymatic (oxidative) release of NO from previously known carbon-bound
      diazeniumdiolates also suggest that analogues of these compounds may be useful as
      pharmaceutical agents. This new method of introducing the relatively rarely
      studied diazeniumdiolate functional group into organic compounds should lead to
      further research into its chemical and biological properties.

PMID- 10970321
TI  - Type-Two intramolecular diels-alder reactions of pyrazolo-o-quinodimethanes
AB  - Two isomeric series of homologous N-(acryloyloxy)alkylated pyrazolo-3-sulfolenes
      10a-c and 18a-c have been efficiently synthesized from a common starting
      material, 4,6-dihydro-1H-thieno[3, 4-c]pyrazole (5). Thermolysis of these fused 3
      sulfolenes provides the corresponding o-quinodimethanes which simultaneously
      undergo "type-two" intramolecular Diels-Alder reactions to form two- and three
      atom-bridged tricyclic pyrazoles which are otherwise difficult to prepare. It was
      also demostrated that, depending on the N-substitution position of the pyrazolo
      fused 3-sulfolenes, the temperature required for the thermal extrusion of SO(2)
      and the regioselectivity of the T2-IMDA reactions were influenced substantially.

PMID- 10970322
TI  - Designing large triangular chiral macrocycles: efficient
AB  - Triangular 30- and 27-membered hexaiminomacrocycles 4 and 5 of D(3) and C(3)
      symmetry, respectively, are readily obtained by unprecedented [3 + 3]
      cyclocondensation of (R,R)-1, 2-diaminocyclohexane with, accordingly,
      terephthalaldehyde and isophthalaldehyde. The course of the reaction, leading to
      macrocyclization, is governed by conformational constraints imposed on the
      structural components of the intermediate products, as shown by molecular
      modeling. X-ray analysis of cocrystal 4.AcOEt revealed that the macrocycle
      symmetry significantly departs from ideal D(3) symmetry due to crystal
      environment. Cyclic hexaamines 6 and 7 were prepared by sodium borohydride
      reduction of 4 and 5, respectively.

PMID- 10970323
TI  - Total synthesis of (+/-)-2-isocyanoallopupukeanane
AB  - 2-Isocyanoallopupukeanane (4) has been obtained in racemic form from methyl 2-exo
      methylbicyclo[2.2.1]hept-5-ene-2-endo-carboxylate via dibromocarbene addition,
      S(N)2' displacement, chain extension, and elaboration of the unsaturated ketone
      12c which underwent an intramolecular hetero-Diels-Alder reaction to afford 13
      containing all the skeletal carbon atoms. The dihydropyran unit was cleaved by
      ozonolysis to give the tricarbocyclic intermediate which required seven more
      steps to complete the synthesis.

PMID- 10970324
TI  - Dimethyl azo(bisisobutyrate) and C(60) produce 1,4- and 1, 16-Di(2-carbomethoxy-2
      propyl)-1,x-dihydro
AB  - Thermal decomposition of dimethyl azo(bisisobutyrate) in a solution containing
      C(60) produced 1,4- and 1, 16-di(2-carbomethoxy-2-propyl)-1,x
      dihydro[60]fullerenes in yields of 21% and 27%, respectively, based on reacted
      C(60). The structure of this first 1,16-dialkyl-1,16-dihydro[60]fullerene was
      assigned from (13)C 2D INADEQUATE NMR spectra. The 1,16-isomer has first and
      second electrochemical reduction potentials shifted positively by 0. 18 V
      relative to those of the 1,4-isomer. From the close similarity of all spectral,
      chromatographic, and electrochemical data, the previously unassigned isomer of
      1,x-di(2-cyano-2-propyl)-1, x-dihydro[60]fullerene, which was obtained from
      azo(bisisobutyronitrile) and C(60), is also a 1,16-isomer.

PMID- 10970325
TI  - Total syntheses of (+)-australine and (-)-7-epialexine.
AB  - Three approaches were examined for the synthesis of 3
      (hydroxymethyl)pyrrolizidines, a class of compounds that includes the
      polyhydroxylated pyrrolizidine alkaloids alexine (1), australine (2), and various
      stereoisomers of thereof. In the first approach, the intramolecular cycloaddition
      of an azide onto an electron-rich 1, 3-diene bearing a terminal alkoxymethyl
      substituent (i.e., 21) afforded the dehydropyrrolizidines 22a and 22b, with 22a
      predominating. A rationale for this stereoselectivity was proposed.
      Transformation of the major diastereomer 22a into a natural 3
      (hydroxymethyl)pyrrolizidine was not possible due to difficulties encountered in
      transforming the phenyl vinyl sulfide functionality into other useful functional
      groups. A second approach was examined, wherein the intramolecular cycloaddition
      of an azide with an optically pure S-t-Bu-substituted diene (i.e., 30) was found
      to produce the pyrrolizidine 31. In this case, the alkoxymethyl substituent was
      incorporated into the tether between the azide and the diene, rather than on the
      diene itself. A key transformation in the synthesis of the diene 30 was the use
      of the allylic borane R(2)BCH(2)CH=C(TMS)(StBu) for the stereoselective
      conversion of the D-arabinose-derived azido aldehyde 28 to the E-isomer of 30.
      The cyclization of 30 to 31 also produced the bicyclic triazene 32, the result of
      1,3-dipolar cycloaddition of the azide onto the distal double bond of the diene.
      Again, difficulties in transformation of the vinyl sulfide functionality of 31
      into useful oxygen functionality limited this approach to naturally occurring 3
      (hydroxymethyl)pyrrolizidines. A third approach to these compounds was
      successful. The transformation of L-xylose into the azido epoxy tosylate 46 was
      accomplished using two Wittig reactions and an epoxidation, in addition to other
      standard functional group manipulations. Reductive double-cyclization of 46
      afforded the pyrrolizidines 47a and 47b, which were debenzylated to afford (+)
      australine 2 and (-)-7-epialexine 4, respectively. In the preliminary report of
      this work, erroneous spectroscopic data in the original literature on the
      structural assignment of australine led to the conclusion that the synthetic
      material obtained herein was actually (+)-7-epiaustraline. Recently corrected
      spectroscopic data have appeared which verify that (+)-australine 2 was indeed
      synthesized for the first time.

PMID- 10970326
TI  - Pyrrolo-annelated tetrathiafulvalenes: the parent systems
AB  - The synthesis of a number pyrrolo-annelated tetrathiafulvalenes, including the
      parent bis(pyrrolo[3,4-d])tetrathiafulvalene (7) is decribed. Starting from
      readily available 4,5-bis(bromomethyl)-1, 3-dithiole-2-thione (14) and sodium
      tosylamide, the parent 7 and the asymmetric monopyrrolo tetrathiafulvalenes 23a,b
      were prepared in good yields via a nonclassical and simple pyrrole synthesis.
      Furthermore, a series of asymmetrical N-alkylated
      monopyrrolo/monodihydropyrrolotetrathiafulvalenes was prepared starting from
      primary amines and 14. A detailed study of the fundamental redox behavior of this
      class of heterocycles is reported. NMR spectroscopy, cyclic voltammetry, and PM3
      MO calculations revealed that the pyrrolo-annelated tetrathiafulvalenes have
      highly extended pi-surfaces. The X-ray crystallographic analyses of the
      monopyrrolo tetrathiafulvalenes 22b and 24b, together with preliminary formation
      of a charge-transfer complex between the parent donor 7 and TCNQ, are also
      reported.

PMID- 10970327
TI  - Concurrent induction of two chiral centers from symmetrical 3, 4-disubstituted
      and 3,3,4-trisubstituted 4-pentenals using Rh-catalyzed asymmetric cyclizations
AB  - Asymmetric cyclization of symmetrical 3,4-disubstituted and 3,3, 4-trisubstituted
      4-pentenals was studied using Rh-complexes with chiral ligands. The cyclization
      of symmetrical 4-pentenals 4a,b by a neutral Rh[(R)-BINAP]Cl afforded cis-3,4
      disubstituted (4R)-cyclopentanones 9a,b of >95% ee in 25-31% yields; on the other
      hand, the cyclization of 4a-c by a cationic Rh[(R)-BINAP]ClO(4) afforded trans
      3,4-disubstituted (4S)-cyclopentanones 10a-c of >95% ee in 70-81% yields. All
      stereoisomers could be stereoselectively made by the selection of a neutral or
      cationic Rh-complex, and (R)- or (S)-BINAP ligand. The Rh-catalyzed cyclization
      could be applied to the construction of cyclopentanones 17 and 18 bearing a
      chiral quaternary carbon. The cyclization by the cationic Rh[(R)-BINAP]ClO(4)
      afforded the optically active trans-3,3, 4-trisubstituted cyclopentanones 18a-c
      of 92-95% ee in 75-83% yields. The catalytic cycle was also studied by using
      deuterium aldehyde, and the tentative mechanisms of the enantio- and
      diastereoselection were proposed.

PMID- 10970329
TI  - Theoretical study of intramolecular aldol condensation of 1, 6-diketones:
      trimethylsilyl substituent effect
AB  - Diastereoselective intramolecular aldol condensations are investigated in an
      experimental and computational study of 1, 6-diketones. Ab initio results show
      the importance of the acid medium and disapprove the possibility of a spontaneous
      cyclization, even for silylated compounds. The combination of both experimental
      and computational approaches brings valuable information on the mechanism and on
      the selectivity of the aldol reaction. It is found that the enolization of the
      diketone is a key step in acid-catalyzed mechanism. The cyclization step bears a
      very small activation energy. The dehydration of the aldols are discussed.

PMID- 10970328
TI  - Diastereoselective ring-closing metathesis in the synthesis of dihydropyrans
AB  - An investigation into the factors influencing the diastereochemical outcome of
      the ring-closing metathesis based synthesis of dihydropyrans is presented in this
      paper. Divinyl carbinols derived from alpha-hydroxy carboxylic acid esters are
      elaborated to trienes with two diastereotopic vinyl moieties. Depending on the
      steric demand of the oxo substituent of the divinyl carbinol moiety (either
      unprotected OH, TBDMS, or benzyl ether) different diastereomers are preferrably
      formed upon ring-closing metathesis. An extension to diastereoselective double
      ring-closing metathesis in the formation of spirocycles has also been
      investigated.

PMID- 10970330
TI  - A direct retro-barbier fragmentation

PMID- 10970332
TI  - Solvent effects on the monobromination of alpha,omega-diols: A convenient
      preparation of omega-bromoalkanols

PMID- 10970331
TI  - Highly efficient selective monohydrolysis of symmetric diesters

PMID- 10970333
TI  - Verrillin: a highly oxygenated marine diterpene based on the novel verrillane
      carbon skeleton.

PMID- 10970335
TI  - Optimized synthesis of cavitand phenol bowls

PMID- 10970334
TI  - A one-step synthesis of monoprotected polyethylene glycol ethers.

PMID- 10970336
TI  - A new synthetic methodology for tiazofurin.

PMID- 10970337
TI  - Regioselective ring opening of malic acid anhydrides by carbon nucleophiles.
      Application In the synthesis of chiral tetronic acids

PMID- 10970339
TI  - Synthesis of aryldifluoromethylphosphonothioic acids from O, O-diethyl
      aryldifluoromethylphosphonothioates

PMID- 10970338
TI  - First TiCl(4)-mediated diastereoselective reduction of alpha-nitro ketones to
      anti-beta-nitro alcohols by BH(3).SMe(2)

PMID- 10970340
TI  - Synthesis and optical properties of cross-conjugated
      bis(dimethylaminophenyl)pyridylvinylene derivatives

PMID- 10970341
TI  - Highly stereo- and regioselective allylations catalyzed by Mo-pyridylamide
      complexes: electronic and steric effects of the ligand

PMID- 10970343
TI  - Effect of ligand structure in the bisoxazoline mediated asymmetric addition of
      methyllithium to imines

PMID- 10970344
TI  - Enantioselective reduction of oxime ethers with borane catalyzed by polymer
      supported 2-piperazinemethanol

PMID- 10970342
TI  - Synthesis of 3, 4-O-isopropylidene- (3S,4S)-dihydroxy-(2R,5R)-
      bis(diphenylphosphino)hexane and its application in Rh-catalyzed highly
      enantioselective hydrogenation of enamides.

PMID- 10970345
TI  - Synthesis and functionalization of double picket fence porphyrins starting from
      4,6-disubstituted pyrimidine-5-carbaldehydes

PMID- 10970346
TI  - A universal organic solvation model

PMID- 10970347
TI  - Clinical relevance of direct quantification of pp65 antigenemia using flow
      cytometry in solid organ and stem cell transplant recipients.
AB  - A total of 1,305 blood samples from 85 solid organ transplant (SOT) recipients
      and 25 stem cell transplant (SCT) recipients at risk for cytomegalovirus (CMV)
      infection were prospectively collected and tested using the shell vial assay
      (SVA) and a leukocytic qualitative PCR (q-PCR). Of these, 462 specimens were
      further tested by direct quantification of CMV antigenemia by flow cytometry (FC
      Ag), 125 were tested with a quantitative competitive PCR, and 200 were tested for
      pp65 antigenemia using the slide method (S-Ag). Laboratory data were
      statistically analyzed according to the presence of CMV-related symptoms. In SOT
      and SCT recipients, active CMV infection occurred in 63.5 and 36%, respectively,
      and CMV disease occurred in 53 and 24%, respectively. FC-Ag results correlated
      better with q-PCR and S-Ag than with SVA. The first test found to be positive
      during follow-up was FC-Ag in 73% of cases. In SOT recipients, FC-Ag showed the
      highest sensitivity and negative predictive value for the diagnosis of any grade
      of CMV disease. For FC-Ag, the threshold beyond which CMV disease was highly
      probable seemed to lie at 0.20% positive polymorphonuclear leukocytes. FC-Ag
      appears to be a useful test for the early detection of CMV infection and the
      prediction of CMV disease.

PMID- 10970348
TI  - Role of IS6110-targeted PCR, culture, biochemical, clinical, and immunological
      criteria for diagnosis of tuberculous meningitis.
AB  - An open prospective clinical, microbiological, and molecular analysis of a
      national molecular diagnostic service for tuberculous meningitis (TBM) using an
      in-house IS6110-targeted PCR for molecular "Fastrack" diagnosis was carried out.
      Between April 1997 and June 1998. Consecutive cerebrospinal fluid (CSF) samples
      from 131 patients were assessed. Against a culture on the same sample, PCR had a
      sensitivity of 75% and a specificity of 94%. Of samples from patients classified
      as definite or probable TBM cases based on clinical criteria, 81% had raised CSF
      protein levels and 73% had a lymphocytosis, although 57% of all submitted samples
      showed a raised lymphocyte count. While only 46% had a CSF glucose level below
      the normal range, the CSF glucose level was significantly lower (P = 0. 0281)
      than in cases of meningitis of other etiologies. Levels of tumor necrosis factor
      alpha were also found to be significantly raised in definite or probable TBM
      cases (P = 0.028), while adenosine deaminase levels were not. The study showed
      IS6110-targeted PCR to be a rapid, sensitive, and specific test in routine use
      for the diagnosis of TBM.

PMID- 10970349
TI  - Improved identification and differentiation of varicella-zoster virus (VZV) wild
      type strains and an attenuated varicella vaccine strain using a VZV open reading
      frame 62-based PCR.
AB  - A new method was developed to identify and differentiate varicella-zoster virus
      (VZV) wild-type strains from the attenuated varicella Oka vaccine strain. The PCR
      technique was used to amplify a VZV open reading frame (ORF) 62 region. A single
      specific amplicon of 268 bp was obtained from 71 VZV clinical isolates and
      several laboratory strains. Subsequent digestion of the VZV ORF 62 amplicons with
      SmaI enabled accurate strain differentiation (three SmaI sites were present in
      amplicons of vaccine strain VZV, compared with two enzyme cleavage sites for all
      other VZV strains tested). This method accurately differentiated the Oka vaccine
      strain from wild-type VZV strains circulating in countries representing all six
      populated continents. Moreover, the assay more reliably distinguished wild-type
      Japanese strains from the vaccine strain than did previously described methods.

PMID- 10970350
TI  - Relationship between mutations in dihydropteroate synthase of Pneumocystis
      carinii f. sp. hominis isolates in Japan and resistance to sulfonamide therapy.
AB  - We examined mutations in the dihydropteroate synthase (DHPS) genes of
      Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24
      patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified
      at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients.
      The underlying diseases for these six patients were human immunodeficiency virus
      type 1 infection (n = 4) or malignant lymphoma (n = 2). This frequency was almost
      the same as those reported in Denmark and the United States. None of the six
      patients whose isolates had DHPS mutations were recently exposed to sulfa drugs
      before they developed the current episode of PCP, suggesting that DHPS mutations
      not only are selected by the pressure of sulfa agents but may be incidentally
      acquired. Co-trimoxazole treatment failed more frequently in patients whose
      isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n =
      4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS
      mutations may contribute to failures of co-trimoxazole treatment for PCP.

PMID- 10970351
TI  - DNA-Based diagnostic approaches for identification of Burkholderia cepacia
      complex, Burkholderia vietnamiensis, Burkholderia multivorans, Burkholderia
      stabilis, and Burkholderia cepacia genomovars I and III.
AB  - Bacteria of the Burkholderia cepacia complex consist of five discrete genomic
      species, including genomovars I and III and three new species: Burkholderia
      multivorans (formerly genomovar II), Burkholderia stabilis (formerly genomovar
      IV), and Burkholderia vietnamiensis (formerly genomovar V). Strains of all five
      genomovars are capable of causing opportunistic human infection, and
      microbiological identification of these closely related species is difficult. The
      16S rRNA gene (16S rDNA) and recA gene of these bacteria were examined in order
      to develop rapid tests for genomovar identification. Restriction fragment length
      polymorphism (RFLP) analysis of PCR-amplified 16S rDNA revealed sequence
      polymorphisms capable of identifying B. multivorans and B. vietnamiensis but
      insufficient to discriminate strains of B. cepacia genomovars I and III and B.
      stabilis. RFLP analysis of PCR-amplified recA demonstrated sufficient nucleotide
      sequence variation to enable separation of strains of all five B. cepacia complex
      genomovars. Complete recA nucleotide sequences were obtained for 20 strains
      representative of the diversity of the B. cepacia complex. Construction of a recA
      phylogenetic tree identified six distinct clusters (recA groups): B. multivorans,
      B. vietnamiensis, B. stabilis, genomovar I, and the subdivision of genomovar III
      isolates into two recA groups, III-A and III-B. Alignment of recA sequences
      enabled the design of PCR primers for the specific detection of each of the six
      latter recA groups. The recA gene was found on the largest chromosome within the
      genome of B. cepacia complex strains and, in contrast to the findings of a
      previous study, only a single copy of the gene was present. In conclusion,
      analysis of the recA gene of the B. cepacia complex provides a rapid and robust
      nucleotide sequence-based approach to identify and classify this taxonomically
      complex group of opportunistic pathogens.

PMID- 10970352
TI  - Cutaneous microenvironment of human immunodeficiency virus (HIV)-seropositive and
      HIV-seronegative individuals, with special reference to Staphylococcus aureus
      colonization.
AB  - A cross-sectional quantitative study of cutaneous bacterial and yeast flora at
      seven body sites in 99 human immunodeficiency virus-seropositive and 50
      seronegative military personnel was performed. Statistically significant
      differences in carriage rates were only observed for Staphylococcus aureus on the
      foreheads of seropositive individuals. Seronegative individuals demonstrated
      staphylococcal carriage rates 1.3 to 2 times as great as those of historical
      controls (defined as healthy individuals not receiving any medications) at five
      of six body sites. We conclude that seropositive military personnel do not
      exhibit statistically significant elevations in densities and carriage rates of
      the microorganisms examined (except Staphylococcus aureus), relative to
      seronegative individuals. Seropositive individuals may be predisposed to
      staphylococcal carriage. The elevated staphylococcal carriage rates of military
      personnel undergoing basic training warrants a formal evaluation of the impact of
      training exercises on cutaneous flora. The information gained may serve to limit
      the spread of infection during training exercises and battlefield conditions.

PMID- 10970353
TI  - Phenotypic and genotypic diversity of the flagellin gene (fliC) among Clostridium
      difficile isolates from different serogroups.
AB  - Phenotypic and genotypic diversity of the flagellin gene (fliC) of Clostridium
      difficile was studied in 47 isolates from various origins belonging to the
      serogroups A, B, C, D, F, G, H, I, K, X, and S3. Electron microscopy revealed 17
      nonflagellated strains and 30 flagellated strains. PCR and reverse transcription
      PCR demonstrated that the flagellin gene was present in all strains and that the
      fliC gene was expressed in both flagellated and nonflagellated strains. Southern
      blotting showed the presence of only one copy of the gene and three different
      hybridization patterns. DNA sequence analysis of fliC from the strains belonging
      to serogroups C, D, and X, representative of each profile, disclosed great
      variability in the central domain, whereas the N- and C-terminal domains were
      conserved. The variability of the flagellin gene fliC was further studied in the
      isolates by PCR-restriction fragment length polymorphism (RFLP) analysis. Nine
      different RFLP groups were identified (I to IX), among which three (I, VII, and
      VIII) corresponded to numerous serogroups whereas the six others (II, III, IV, V,
      VI, and IX) belonged to a single serogroup. Flagellin gene RFLP analysis could
      constitute an additional typing method employable in conjunction with other
      typing methods currently available.

PMID- 10970354
TI  - Diagnosis of varicella-zoster virus infections in the clinical laboratory by
      LightCycler PCR.
AB  - Varicella-zoster virus (VZV) causes vesicular dermal lesions which are clinically
      evident as varicella (primary infection) or zoster (reactivated) diseases. The
      LightCycler system (Roche Molecular Biochemicals) is a newly developed
      commercially available system designed to rapidly perform PCR with real-time
      detection of PCR products using a fluorescence resonance energy transfer. We
      compared the detection of VZV from dermal specimens by shell vial cell culture
      (MRC-5) and by LightCycler PCR. Of 253 specimens, VZV was detected in 23 (9.1%)
      by shell vial cell cultures and 44 (17.4%) by LightCycler PCR directed to a
      nucleic acid target sequence in gene 28. Twenty-one of 44 (47.7%) specimens were
      exclusively positive by LightCycler PCR; the shell vial cell culture assay was
      never positive when DNA amplification was negative (specificity, 100%). VZV DNA
      was detected in 39 of 44 (88.6%) specimens positive during cycles 10 through 30
      of the LightCycler PCR. These VZV DNA-positive specimens (cycles 10 to 30) and 5
      of 11 other PCR positive specimens (cycles 31 to 36) were confirmed by another
      LightCycler PCR directed to another (gene 29) target of the viral genome. For
      routine laboratory practice, all specimens yielding amplified DNA to the VZV gene
      28 target can be considered positive results. The increased sensitivity (91%) of
      the LightCycler PCR for detection of VZV, rapid turnaround time for reporting
      results, virtual elimination of amplicon carryover contamination, and equivalent
      costs compared to shell vial cell culture for detection of VZV indicate the need
      for implementation of this technology for routine laboratory diagnosis of this
      viral infection.

PMID- 10970355
TI  - Small subunit ribosomal DNA sequence shows Paracoccidioides brasiliensis closely
      related to Blastomyces dermatitidis.
AB  - The similarities of paracoccidioidomycosis and blastomycosis are highly
      suggestive of a close relation of the two etiological agents. Whereas the agent
      of the first disease is exclusively endemic in Latin America, the agent of the
      latter one is endemic in North America and Africa. In symptomatic travelers
      visiting both areas of endemicity, differentiation of the diseases might be
      impossible, even though therapy and prognosis for these two diseases differ
      significantly. In order to identify differences in the 18S rRNA gene (rDNA) for
      use as molecular diagnostic tools, we sequenced this gene from five isolates of
      Paracoccidioides brasiliensis and compared them to known sequences of other
      fungi. Neighbor-joining, maximum parsimony, and maximum likelihood analyses and,
      finally, the Kishino-Hasegawa test revealed that P. brasiliensis, Blastomyces
      dermatitidis, and Emmonsia parva are more closely related than Histoplasma
      capsulatum and B. dermatitidis, whose teleomorphic forms belong to one genus,
      Ajellomyces. In accordance with the work of other investigators who have used
      internal transcribed spacer and large subunit rDNA sequences, our small subunit
      rDNA data show that the dimorphic fungus P. brasiliensis must be grouped within
      the order Onygenales and is closely related to members of the family Onygenaceae.
      There are hints in the molecular phylogenetic analysis that the family
      Onygenaceae might be further divided into two families. The subgroup that
      includes P. brasiliensis comprises all zoopathogenic species. The differences in
      the 18S rDNAs appear to be too small to allow species identification of the
      members of the family Onygenaceae pathogenic for humans by use of target
      sequences within this gene.

PMID- 10970356
TI  - Use of real-time PCR and fluorimetry for rapid detection of rifampin and
      isoniazid resistance-associated mutations in Mycobacterium tuberculosis.
AB  - Very fast amplification of DNA in small volumes can be continuously monitored
      with a rapid cycler that incorporates fluorimetric detection. Primers were
      designed to amplify a 157-bp fragment of the rpoB gene spanning codons 526 and
      531 and a 209-bp fragment of the katG gene spanning codon 315 of Mycobacterium
      tuberculosis. Most mutations associated with resistance to rifampin (RMP) and
      isoniazid (INH) in clinical isolates occur in these codons. Two pairs of
      hybridization probes were synthesized; one in each pair was 3' labeled with
      fluorescein and hybridized upstream of the codon with the mutation; the other two
      probes were 5' labeled with LightCycler-Red 640. Each pair of probes recognized
      adjacent sequences in the amplicon. After DNA amplification was finished by using
      a LightCycler, the temperature at which the Red 640 probe melted from the product
      was determined in a 3-min melt program. Twenty M. tuberculosis clinical isolates
      susceptible to streptomycin, INH, RMP, and ethambutol and 36 antibiotic-resistant
      clinical M. tuberculosis isolates (16 resistant to RMP, 16 to INH, and 4 to both
      antimicrobial agents) were amplified, and the presence of mutations was
      determined using single-strand conformation polymorphism analysis, the LiQor
      automated sequencer, and the LightCycler system. Concordant results were obtained
      in all cases. Within 30 min, the LightCycler method correctly genotyped all the
      strains without the need of any post-PCR sample manipulation. Overall, this pilot
      study demonstrated that real-time PCR coupled to fluorescence detection is the
      fastest available method for the detection of RMP and INH resistance-associated
      mutations in M. tuberculosis clinical isolates.

PMID- 10970357
TI  - Molecular characterization of Mycobacterium tuberculosis H37Rv/Ra variants:
      distinguishing the mycobacterial laboratory strain.
AB  - The Mycobacterium tuberculosis strains H37Rv and H37Ra are the most commonly used
      controls for M. tuberculosis identification in the clinical and research
      laboratory setting. To reduce the likelihood of misidentification and possible
      cross-contamination with this laboratory neotype, it is important to be able to
      distinguish H37 from clinical isolates. To provide a reference for identifying
      H37, we used multiple molecular techniques to characterize H37 strains, including
      18 of the most frequently used variants available through the American Type
      Culture Collection. Isolates were genotyped using gene probes to IS6110 and
      IS1085. In addition, we performed polymorphic GC-rich sequence typing (PGRS),
      spoligotyping, determination of variable number of tandem repeats (VNTR), and PCR
      amplification of the mtp40, msx4, and mpp8 polymorphic regions. Southern
      hybridization with IS6110 provided the most discrimination, differentiating the
      18 H37 isolates into 10 discrete patterns made up of 9 H37Rv variants and 1 H37Ra
      variant. PGRS, IS1085, mpp8, and spoligotyping were not able to distinguish any
      H37 variants, while VNTR and msx4 discriminated two. Only IS6110 and
      spoligotyping could distinguish the H37 strain from clinical isolates. In
      summary, spoligotyping and IS6110 provide a rapid and accurate way to identify
      H37 contamination, though IS6110 can, in addition, classify many of the H37
      variants that would otherwise require phenotypic segregation.

PMID- 10970358
TI  - Comparison of three different sensitive assays for hepatitis B virus DNA in
      monitoring of responses to antiviral therapy.
AB  - The aim of our study was to compare the performances of two new hepatitis B virus
      (HBV) DNA assays, a cross-linking assay (NAXCOR) and a hybrid-capture
      amplification assay (Digene), versus the widely used branched-DNA (bDNA) assay
      (Chiron) in the monitoring of HBV DNA levels during antiviral treatment. Serial
      serum samples from 12 chronically HBV infected patients undergoing a phase II
      trial of an antiviral drug, 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), were
      studied. A total of 96 serum samples were tested for HBV DNA using the cross
      linking, hybrid-capture amplification, and bDNA assays. In the comparison of the
      cross-linking and bDNA assays, concordant results were found in 77 (80.3%)
      samples, no significant difference was found between the median log(10) HBV DNA
      levels (6.66 versus 7. 17 meq/ml), and the results of the two assays were closely
      correlated (r = 0.95). In the comparison of the hybrid-capture amplification and
      bDNA assays, concordant results were found in 79 (82.3%) samples, no significant
      difference was found between the median log(10) HBV DNA levels (6.98 versus 6.99
      meq/ml), and the results of the two assays were closely correlated (r = 0.99).
      Six (6. 3%) samples by the cross-linking assay and 10 (10.4%) samples by the bDNA
      assay required retesting because of unacceptably high within-run coefficients of
      variance. No sample required retesting in the hybrid-capture amplification assay
      according to the internal validation. In conclusion, the cross-linking and hybrid
      capture amplification assays were as sensitive as the bDNA assay for HBV DNA
      detection and can be recommended for monitoring of HBV DNA levels during
      antiviral treatment.

PMID- 10970359
TI  - PCR-restriction fragment length polymorphism analysis for identification of
      Bacteroides spp. and characterization of nitroimidazole resistance genes.
AB  - Bacteroides spp. are opportunist pathogens that cause blood and soft tissue
      infections and are often resistant to antimicrobial agents. We have developed a
      combined PCR-restriction fragment length polymorphism (RFLP) technique to
      characterize the 16S rRNA gene for identification purposes and the nitroimidazole
      resistance (nim) gene for detection of resistance to the major antimicrobial
      agent used to treat Bacteroides infections: metronidazole (MTZ). PCR-RFLP
      analysis of 16S ribosomal (rDNA) with HpaII and TaqI produced profiles that
      enabled discrimination of type strains and identification of 70 test strains to
      the species level. The 16S rDNA PCR-RFLP identification results agreed with
      routine phenotypic testing for 62 of the strains. The discrepancies between
      phenotypic and PCR-RFLP methods for eight strains were resolved by 16S rDNA
      sequencing in three cases, but five strains remain unidentified. The presence of
      nim genes was indicated by PCR in 25 of 28 strains that exhibited reduced
      sensitivity to MTZ. PCR-RFLP of the nim gene products identified the four
      reported genes (nimA, -B, -C, and -D) and indicated the presence of a previously
      unreported nim gene in 5 strains. This novel nim gene exhibited 75% DNA sequence
      similarity with nimB. These rapid, accurate, and inexpensive methods should
      enable improved identification of Bacteroides spp. and the detection of MTZ
      resistance determinants.

PMID- 10970360
TI  - Time-resolved fluorometry PCR assay for rapid detection of herpes simplex virus
      in cerebrospinal fluid.
AB  - We have introduced a time-resolved fluorometry (TRF)-based microwell
      hybridization assay for PCR products in detection of herpes simplex virus (HSV)
      in cerebrospinal fluid (CSF) specimens. TRF is a sensitive nonradioactive
      detection technique which involves the use of lanthanide chelates as fluorescent
      labels. We used PCR primers from the glycoprotein D genes of HSV type 1 (HSV-1)
      and HSV-2. The biotinylated PCR products were collected on streptavidin-coated
      microtitration wells and hybridized with short oligonucleotide probes, europium
      labeled for HSV-1 and samarium labeled for HSV-2. The TRF results were obtained
      as counts per second and as signal-to-noise (S/N) ratios. The sensitivity of the
      assay was 0.1 infectious units (PFU) of HSV in CSF specimens, and the S/N values
      increased with the virus amount, up to 68.5 for 10(3) PFU of HSV-1 and to 58.5
      for 10(3) PFU of HSV-2, allowing semiquantitation of HSV in CSF. The primers and
      probes recognized all the studied 48 HSV wild-type samples, with S/N ratios of
      12.4 to 190 (HSV-1) and 5.1 to 248 (HSV-2). We tested CSF specimens, 100 for each
      HSV type, which were HSV PCR negative by Southern blot and 22 CSF specimens which
      were HSV-1 or -2 PCR blot positive. In the TRF test, the mean S/N ratio for the
      HSV-1-negative CSF was 1.37 (standard deviation [SD] = 0.513) and for the HSV-2
      negative CSF it was 1.03 (SD = 0.098). The HSV-1 blot-positive CSF yielded S/N
      ratios of 3.6 to 85.9, and the HSV-2 blot-positive CSF yielded ratios from 1.9 to
      13. Using the mean S/N ratio for negative CSF specimens + 3 SD as the cutoff
      yielded all the previously HSV-positive specimens as TRF positive. The TRF PCR
      assay for HSV in CSF specimens is a rapid and sensitive method, improves
      interpretation of PCR results, and is well suited for automation.

PMID- 10970362
TI  - Prevalence and risk factors of tinea unguium and tinea pedis in the general
      population in Spain.
AB  - This study prospectively evaluated the prevalence and risk factors of tinea
      unguium and tinea pedis in the general adult population in Madrid, Spain. One
      thousand subjects were clinically examined, and samples of nails and scales from
      the interdigital spaces of the feet were taken from those patients presenting
      with signs or symptoms of onychomycosis and/or tinea pedis, respectively. In
      addition, a sample from the fourth interdigital space of both feet was collected
      from all individuals with a piece of sterilized wool carpet. Tinea unguium was
      defined as a positive direct examination with potassium hydroxide and culture of
      the etiological agent from subjects with clinically abnormal nails. Patients with
      positive dermatophyte cultures of foot specimens were considered to have tinea
      pedis. The prevalence of tinea unguium was 2.8% (4.0% for men and 1.7% for
      women), and the prevalence of tinea pedis was 2.9% (4.2% for men and 1.7% for
      women). The etiological agents of tinea unguium were identified as Trichopyton
      rubrum (82.1%), followed by Trichopyton mentagrophytes var. interdigitale (14.3%)
      and Trichopyton tonsurans (3.5%). Trichophyton rubrum (44.8%) and Trichophyton
      mentagrophytes (44.8%), followed by Epidermophyton floccosum (7%) and T.
      tonsurans (3.4%), were the organisms isolated from patients with tinea pedis. The
      percentage of subjects who suffered simultaneously from both diseases was 1.1%
      (1.7% for men and 0.6% for women). In a multivariate logistic regression
      analysis, age (relative risk [RR], 1.03) and gender (RR, 2.50) were independent
      risk factors for tinea unguium, while only gender (RR, 2.65) was predictive for
      the occurrence of tinea pedis. In both analyses, the presence of one of the two
      conditions was associated with a higher risk for the appearance of the other
      disease (RR, >25).

PMID- 10970361
TI  - Cloning of the rhesus lymphocryptovirus viral capsid antigen and Epstein-Barr
      virus-encoded small RNA homologues and use in diagnosis of acute and persistent
      infections.
AB  - Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and
      is associated with the development of several human malignancies. A closely
      related herpesvirus in the same lymphocryptovirus (LCV) genera as EBV naturally
      infects rhesus monkeys and provides an important animal model for studying EBV
      pathogenesis. We cloned the small viral capsid antigen (sVCA) homologue from the
      rhesus LCV and developed a peptide enzyme-linked immunosorbent assay (ELISA) to
      determine whether epitopes in the rhesus LCV sVCA are a reliable indicator of
      rhesus LCV infection. In order to define a "gold standard" for rhesus LCV
      infection, we also cloned the EBV-encoded small RNA 1 (EBER1) and EBER2
      homologues from rhesus LCV and developed a reverse transcription (RT)-PCR assay
      to detect persistent LCV infection in rhesus monkey peripheral blood lymphocytes.
      Animals from a conventional and a hand-reared colony were studied to compare the
      prevalence of rhesus LCV infection in the two groups. There was a 100%
      correlation between the peptide ELISA and EBER RT-PCR results for rhesus LCV
      infection. In addition, specificity for LCV infection and exclusion of potential
      cross-reactivity to the rhesus rhadinovirus sVCA homologue could be demonstrated
      using sera from experimentally infected animals. These studies establish two
      novel assays for reliable diagnosis of acute and persistent rhesus LCV
      infections. The rhesus LCV sVCA peptide ELISA provides a sensitive and reliable
      assay for routine screening, and these studies of the hand-reared colony confirm
      the feasibility of raising rhesus LCV-naive animals.

PMID- 10970363
TI  - Differentiation of clinical Mycobacterium tuberculosis complex isolates by gyrB
      DNA sequence polymorphism analysis.
AB  - The discriminatory power of gyrB DNA sequence polymorphisms for differentiation
      of the species of the Mycobacterium tuberculosis complex (MTBC) was evaluated by
      sequencing and restriction fragment length polymorphism (RFLP) analysis of a
      1,020-bp fragment amplified from clinical isolates of M. tuberculosis,
      Mycobacterium bovis (pyrazinamide [PZA] resistant as well as PZA susceptible),
      Mycobacterium africanum subtypes I and II, and Mycobacterium microti types vole
      and llama. We found sequence polymorphisms in four regions described previously
      and at one additional position. These differences in the gyrB sequences allow an
      accurate discrimination of M. bovis, M. microti, and M. africanum subtype I. The
      PZA-susceptible subtypes of M. bovis shared the M. bovis-specific substitution at
      position 756 with the PZA-resistant strains, but can be unambiguously
      differentiated by a characteristic substitution at position 1311. As a drawback,
      M. tuberculosis and M. africanum subtype II showed an identical gyrB sequence
      that facilitates discrimination from the other species, but not from each other.
      A PCR-RFLP technique applying three restriction enzymes could be shown to be a
      rapid and easy-to-perform tool for the differentiation of the members of the
      MTBC. Based on these results, we present a clear diagnostic algorithm for the
      differentiation of species of the MTBC.

PMID- 10970364
TI  - Diagnosis of amebic liver abscess and intestinal infection with the TechLab
      Entamoeba histolytica II antigen detection and antibody tests.
AB  - A noninvasive diagnostic test for amebic liver abscess is needed, because amebic
      and bacterial abscesses appear identical on ultrasound or computer tomography and
      because it is rarely possible to identify Entamoeba histolytica in stool
      specimens from patients with amebic liver abscess. Here we report a method of
      detection in serum of circulating E. histolytica Gal/GalNAc lectin to diagnose
      amebic liver abscess, which was used in patients from Dhaka, Bangladesh. The
      TechLab E. histolytica II test (which differentiates the true pathogen E.
      histolytica from Entamoeba dispar) detected Gal/GalNAc lectin in the sera of 22
      of 23 (96%) amebic liver abscess patients tested prior to treatment with the
      antiamebic drug metronidazole and 0 of 70 (0%) controls. After 1 week of
      treatment with metronidazole, 9 of 11 (82%) patients became serum lectin antigen
      negative. The sensitivity of the E. histolytica II antigen detection test for
      intestinal infection was also evaluated. Antigen detection identified E.
      histolytica infection in 50 samples from 1, 164 asymptomatic preschool children
      aged 2 to 5 years, including 16 of 16 (100%) culture-positive specimens. PCR
      analysis of stool specimens was used to confirm that most antigen-positive but
      culture-negative specimens were true-positive: PCR identified parasite DNA in 27
      of 34 (79%) of the antigen-positive, culture-negative stool specimens. Antigen
      detection was a more sensitive test for infection than antilectin antibodies,
      which were detected in only 76 of 98 (78%) amebic liver abscess patients and in
      26 of 50 (52%) patients with intestinal infection. We conclude that the TechLab
      E. histolytica II kit is a sensitive means to diagnose hepatic and intestinal
      amebiasis prior to the institution of metronidazole treatment.

PMID- 10970365
TI  - Molecular epidemiology of Mycobacterium avium subsp. paratuberculosis: IS900
      restriction fragment length polymorphism and IS1311 polymorphism analyses of
      isolates from animals and a human in Australia.
AB  - The distribution and prevalence of strains of Mycobacterium avium subsp.
      paratuberculosis were determined among sheep, cattle, and other species with
      Johne's disease in Australia. A total of 328 isolates were evaluated from
      numerous farms in New South Wales, Victoria, Tasmania, and South Australia,
      Australia. Restriction fragment length polymorphism (RFLP) analysis of genomic
      DNA using BstEII and an IS900 probe and IS1311 polymorphism analysis using PCR
      and restriction endonuclease analysis (PCR-REA) was used to classify isolates as
      cattle (C) or sheep (S) strains. IS1311 PCR-REA provided similar information to
      IS900 RFLP analysis but was more useful than RFLP analysis where DNA was degraded
      or scarce. Twelve IS900 RFLP types were found. Johne's disease in sheep was
      always due to S strains, while cattle were infected only with C strains. RFLP
      type S1 was the dominant strain in sheep in New South Wales (97% of isolates) and
      was the only strain found in sheep from Victoria. Seven RFLP types were present
      in cattle. RFLP types C3 and C1 were most common (collectively, 85% of isolates),
      but C1 was not found in New South Wales and C3 was present in dairy cattle but
      not in beef cattle in Victoria. These differences may be explained by restricted
      livestock trading patterns between different segments of the cattle industry. Up
      to five RFLP types were present in some geographic regions in Victoria, while up
      to three RFLP types were found among cattle on some farms. Individual cattle
      usually were infected with only one RFLP type, but one animal was infected with
      both C5 and CU4. Two isolates from goats were C type as were three from alpacas,
      one from a rhinoceros, and two from a human with Crohn's disease. The prevalences
      of specific RFLP types in Australia differ from those reported in Europe and
      elsewhere. Given the existence of geographical and farm enterprise differences in
      IS900 RFLP type, this technique may be applied selectively to trace the spread of
      Johne's disease, at least in the cattle industries. As these observations reflect
      past exposure of livestock to M. avium subsp. paratuberculosis, the monitoring of
      strains present in animals in Australia is continuing.

PMID- 10970366
TI  - False-positive results of plasma PCR for cytomegalovirus DNA due to delayed
      sample preparation.
AB  - Positive results by cytomegalovirus (CMV) PCR of plasma are considered predictive
      of active CMV infection in kidney allograft recipients. To assess whether
      contamination with leukocyte-derived CMV DNA can distort the results, aliquots of
      whole-blood samples from 60 CMV immunoglobulin G-positive patients with leukocyte
      CMV DNAemia were stored for up to 24 h at room temperature (RT) and at 4 degrees
      C before plasma preparation. Native and ultrafiltered plasma samples were tested
      by CMV and beta-globin PCRs. Among 30 latently infected patients (negative for
      CMV pp65 antigens), low baseline rates (10%) and levels (median number of copies,
      10 [per 10 microl]) of CMV plasma DNAemia in native plasma samples increased
      significantly over time (after 4 h at RT, 37% [P < 0.001]; median number of
      copies, 45 [P < 0.001]). Similar effects were found during storage at 4 degrees
      C. Ultrafiltration reduced the levels of CMV plasma DNAemia, but by 6 h of
      storage the levels were significantly elevated as well. CMV and beta-globin DNA
      kinetics in plasma were parallel. In contrast, 30 actively infected patients
      (pp65 positive) had high baseline rates (87% in native samples) and levels
      (median number of copies, 75) of CMV plasma DNAemia. No significant effects of
      storage or ultrafiltration and no concordance with beta-globin DNA kinetics were
      seen. In conclusion, delayed preparation of plasma samples bears a significant
      risk of false-positive CMV PCR results, probably due to leukocyte lysis. This has
      important implications in the clinical setting and for PCR standardization.

PMID- 10970367
TI  - Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid
      tissue.
AB  - Ovine scrapie is a member of the transmissible spongiform encephalopathies
      (TSEs), a heterogeneous family of fatal neurologic disorders characterized by
      deposition of an abnormal isoform (prion protein [PrP] PrP-Sc) of a cellular
      sialoglycoprotein in neural tissue. PrP-Sc is detectable in some lymphoid tissues
      of infected sheep months or years before development of clinical disease.
      Detection of PrP-Sc in these tissues is the basis for live-animal testing. In
      this study, we characterize the performance of a preclinical diagnostic test for
      ovine scrapie based on a monoclonal antibody (MAb)-based immunohistochemistry
      assay of nictitating membrane ("third eyelid")-associated lymphoid tissue. The
      results of third eyelid immunohistochemistry assay agreed with the scrapie status
      of the sheep for 41 of 42 clinical suspects with confirmed scrapie and 174 of 175
      sheep without scrapie. Third eyelid sampling agreed with the scrapie status for
      36 of 41 clinically normal sheep positive for PrP-Sc immunostaining of brain
      tissue, including 27 sheep with positive biopsy specimens that progressed to
      clinical disease with confirmed scrapie 3 to 20 months after biopsy. The assay
      used MAb F89/160.1.5, which binds to residues 142 to 145 of ovine PrP. This
      antibody can be used in combination with MAb F99/97. 6.1, which binds to residues
      220 to 225. One or both MAbs in this cocktail recognize PrP sequences conserved
      in most mammalian species in which natural TSEs have been reported.
      Immunohistochemistry assay of routinely formalin-fixed lymphoid tissues with a
      cocktail of pan-specific MAbs is a practical, readily standardized live-animal
      and preclinical test for ovine scrapie.

PMID- 10970368
TI  - Experimental model of progressive disseminated trichosporonosis in mice with
      latent trichosporonemia.
AB  - Trichosporon asahii and Trichosporon mucoides are the most common strains of
      fungi that cause disseminated trichosporonosis, a severe opportunistic infection
      in immunocompromised hosts. We have previously established a nested PCR assay
      using serum samples for detection of both strains. Here we describe a new
      experimental animal model for investigating the underlying mechanisms of
      disseminated trichosporonosis. T. asahii (OMU239, a clinical isolate from a
      patient with acute myelogenous leukemia) and 8-week-old ICR male mice were used
      in all experiments. A suspension of T. asahii (3 x 10(6) CFU/animal) was injected
      into the caudal vein of each mouse after immunosuppression with cyclophosphamide
      (200 mg/kg of body weight/day for 2 days) and prednisolone (30 mg/kg/day for 1
      day). Mice were then divided into four subgroups (R0, R1, R2, and R3) based on
      the time of reimmunosuppression. The latter was performed using the same drugs 1
      week (group R1), 2 weeks (group R2), and 3 weeks (group R3) after fungal
      infection. Reimmunosuppression was not performed in group R0. The 5-week-survival
      rates of mice after T. asahii infection were 0% for group R1, 50% for group R2,
      80% for group R3, and 80% for group R0. There was a significant difference in the
      survival rates between group R1 and either group R0 or R3 (P < 0.05). Fungal
      clearance in peripheral blood and various organs of group R1 and R2 was delayed
      relative to that of group R0 but was similar to the control in group R3 in spite
      of reimmunosuppression. Our results suggest that the critical period for the
      development of disseminated trichosporonosis in our model is shorter than 3 weeks
      after T. asahii infection. We concluded that mice during this critical period
      were in a state of latent trichosporonemia. Comparison of the survival rates
      suggests that the nested PCR assay was more useful than blood culture and
      glucuronoxylomannan antigen assay in the detection of this latent
      trichosporonemia.

PMID- 10970369
TI  - Molecular variability of Pseudallescheria boydii, a neurotropic opportunist.
AB  - The sequences of the internal transcribed spacer (ITS) ribosomal DNA (rDNA)
      domain data obtained by restriction fragment length polymorphism analysis with
      18S rDNA and fingerprinting (M13) for clinical and environmental strains of
      Pseudallescheria boydii (anamorph, Scedosporium apiospermum) were compared to
      those for related species of Pseudallescheria, Petriella, and Scedosporium. The
      infraspecific variability of P. boydii was considerable. There were five
      different lengths in the 18S rDNAs within P. boydii due to the occurrence of
      introns. In several cases, strains isolated from a single pond or ditch proved to
      be genetically very different. Nevertheless, some lineages had a regional
      distribution. The variability found is unlikely to be explained by meiotic
      recombination alone. Pseudallescheria fusoidea, Pseudallescheria ellipsoidea, and
      Pseudallescheria angusta were found to be synonyms for P. boydii. Scedosporium
      prolificans was found amid Petriella species in the ITS tree and showed no
      infraspecific variability. The type strain of Rhinocladium lesnei proved to be
      identical to Graphium putredinis. Acladium castellanii, which is morphologically
      reminiscent of S. apiospermum, was also found to be a separate species, but with
      an unknown affiliation.

PMID- 10970370
TI  - Comprehensive PCR-based assay for detection and species identification of human
      herpesviruses.
AB  - The description and evaluation of a PCR-based assay for the detection and species
      identification of the eight known human herpesviruses are presented. Two primer
      pairs targeting well-conserved regions of the genome allowed the amplification of
      the DNAs of all known human herpesviruses at a high level of sensitivity (10 to
      100 genome copies for most viruses). Identification of the virus species was
      achieved through restriction enzyme digestion with BamHI and BstUI, which yielded
      fragment sizes that were characteristic for each herpesvirus. Furthermore, it was
      demonstrated that this restriction enzyme panel allowed the discrimination
      between human herpesvirus 6 variant A and variant B. This assay format was
      validated over the course of 1 year in a clinical virology laboratory setting,
      where it was shown that it readily detected human herpesviruses, including
      occasional multiple infections, in a variety of clinical samples. The PCR assay
      was compared to isolation and electron microscopy for the detection of herpes
      simplex (HSV) and varicella-zoster virus (VZV) in clinical samples. All specimens
      positive by conventional methods were also positive by PCR. However, in a number
      of clinical specimens in which HSV or VZV could not be detected by conventional
      methods, PCR was able to demonstrate the presence of the virus.

PMID- 10970371
TI  - Development of a rapid PCR assay specific for Staphylococcus saprophyticus and
      application to direct detection from urine samples.
AB  - Staphylococcus saprophyticus is one of the most frequently encountered
      microorganisms associated with acute urinary tract infections (UTIs) in young,
      sexually active female outpatients. Conventional identification methods based on
      biochemical characteristics can efficiently identify S. saprophyticus, but the
      rapidities of these methods need to be improved. Rapid and direct identification
      of this bacterium from urine samples would be useful to improve time required for
      the diagnosis of S. saprophyticus infections in the clinical microbiology
      laboratory. We have developed a PCR-based assay for the specific detection of S.
      saprophyticus. An arbitrarily primed PCR amplification product of 380 bp specific
      for S. saprophyticus was sequenced and used to design a set of S. saprophyticus
      specific PCR amplification primers. The PCR assay was specific for S.
      saprophyticus when tested with DNA from 49 gram-positive and 31 gram-negative
      bacterial species. This assay was also able to amplify efficiently DNA from all
      60 strains of S. saprophyticus from various origins tested. This assay was
      adapted for direct detection from urine samples. The sensitivity levels achieved
      with urine samples was 19 CFU with 30 cycles of amplification and 0.5 CFU with 40
      cycles of amplification. This PCR assay for the specific detection of S.
      saprophyticus is simple and rapid (approximately 90 min, including the time for
      urine specimen preparation).

PMID- 10970372
TI  - Molecular and immunological characterization of Mycobacterium tuberculosis CFP
      10, an immunodiagnostic antigen missing in Mycobacterium bovis BCG.
AB  - In order to identify antigens that may be used in the serodiagnosis of active
      tuberculosis (TB), we screened a Mycobacterium tuberculosis genomic expression
      library with a pool of sera from patients diagnosed with active pulmonary TB. The
      sera used lacked reactivity with a recombinant form of the M. tuberculosis 38-kDa
      antigen (r38kDa), and the goal was to identify antigens that might complement
      r38kDa in a serodiagnostic assay. Utilizing this strategy, we identified a gene,
      previously designated lhp, which encodes a 100-amino-acid protein referred to as
      culture filtrate protein 10 (CFP-10). The lhp gene is located directly upstream
      of esat-6, within a region missing in M. bovis BCG. Immunoblot analysis
      demonstrated that CFP-10 is present in M. tuberculosis CFP, indicating that it is
      likely a secreted or shed antigen. Purified recombinant CFP-10 (rCFP-10) was
      shown to be capable of detecting specific antibody in a percentage of TB patients
      that lack reactivity with r38kDa, most notably in smear-negative cases, where
      sensitivity was increased from 21% for r38kDa alone to 40% with the inclusion of
      rCFP-10. In smear-positive patient sera, sensitivity was increased from 49% for
      r38kDa alone to 58% with the inclusion of rCFP-10. In addition, rCFP-10 was shown
      to be a potent T-cell antigen, eliciting proliferative responses and gamma
      interferon production from peripheral blood mononuclear cells in 70% of purified
      protein derivative-positive individuals without evident disease. The responses to
      this antigen argue for the inclusion of rCFP-10 in a polyvalent serodiagnostic
      test for detection of active TB infection. rCFP-10 could also contribute to the
      development of a recombinant T-cell diagnostic test capable of detecting exposure
      to M. tuberculosis.

PMID- 10970373
TI  - Coronavirus and Pasteurella infections in bovine shipping fever pneumonia and
      Evans' criteria for causation.
AB  - Respiratory tract infections with viruses and Pasteurella spp. were determined
      sequentially among 26 cattle that died during two severe epizootics of shipping
      fever pneumonia. Nasal swab and serum samples were collected prior to onset of
      the epizootics, during disease progression, and after death, when necropsies were
      performed and lung samples were collected. Eighteen normal control cattle also
      were sampled at the beginning of the epizootics as well as at weekly intervals
      for 4 weeks. Respiratory bovine coronaviruses (RBCV) were isolated from nasal
      secretions of 21 and 25 cattle before and after transport. Two and 17 cattle
      nasally shed Pasteurella spp. before and after transport, respectively. RBCV were
      isolated at titers of 1 x 10(3) to 1.2 x 10(7) PFU per g of lung tissue from 18
      cattle that died within 7 days of the epizootics, but not from the lungs of the
      remaining cattle that died on days 9 to 36. Twenty-five of the 26 lung samples
      were positive for Pasteurella spp., and their CFU ranged between 4.0 x 10(5) and
      2.3 x 10(9) per g. Acute and subacute exudative, necrotizing lobar pneumonia
      characterized the lung lesions of these cattle with a majority of pneumonic lung
      lobes exhibiting fibronecrotic and exudative changes typical of pneumonic
      pasteurellosis, but other lung lobules had histological changes consisting of
      bronchiolitis and alveolitis typical of virus-induced changes. These cattle were
      immunologically naive to both infectious agents at the onset of the epizootics,
      but those that died after day 7 had rising antibody titers against RBCV and
      Pasteurella haemolytica. In contrast, the 18 clinically normal and RBCV isolation
      negative cattle had high hemagglutinin inhibition antibody titers to RBCV from
      the beginning, while their antibody responses to P. haemolytica antigens were
      delayed. Evans' criteria for causation were applied to our findings because of
      the multifactorial nature of shipping fever pneumonia. This analysis identified
      RBCV as the primary inciting cause in these two epizootics. These viruses were
      previously not recognized as a causative agent in this complex respiratory tract
      disease of cattle.

PMID- 10970374
TI  - Characterization of a nosocomial outbreak caused by a multiresistant
      Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level
      carbapenem resistance in A. baumannii is not due solely to the presence of beta
      lactamases.
AB  - From February to November 1997, 29 inpatients at Ramon y Cajal Hospital, Madrid,
      Spain, were determined to be either colonized or infected with imipenem- and
      meropenem-resistant Acinetobacter baumannii (IMRAB) strains (MICs, 128 to 256
      microg/ml). A wide antibiotic multiresistance profile was observed with IMRAB
      strains. For typing IMRAB isolates, pulsed-field gel electrophoresis was used.
      For comparative purposes, 30 imipenem- and meropenem-susceptible A. baumannii
      (IMSAB) strains isolated before, during, and after the outbreak were included in
      this study. The molecular-typing results showed that the outbreak was caused by a
      single IMRAB strain (genotype A). By cloning experiments we identified a class D
      beta-lactamase (OXA-24) encoded in the chromosomal DNA of this IMRAB strain which
      showed carbapenem hydrolysis. Moreover, the outer membrane profile of the IMRAB
      strain showed a reduction in the expression of two porins at 22 and 33 kDa when
      compared with genetically related IMSAB isolates. In addition no efflux
      mechanisms were identified in the IMRAB strains. In summary, we report here the
      molecular characterization of a nosocomial outbreak caused by one multiresistant
      A. baumannii epidemic strain that harbors a carbapenem-hydrolyzing enzyme.
      Although alterations in the penicillin-binding proteins cannot be ruled out, the
      reduction in the expression of two porins and the presence of this OXA-derived
      beta-lactamase are involved in the carbapenem resistance of the epidemic
      nosocomial IMRAB strain.

PMID- 10970375
TI  - Quantitative competitive reverse transcription-PCR for quantification of dengue
      virus RNA.
AB  - A quantitative competitive reverse transcription-PCR assay was developed to
      quantify dengue virus RNA in this study. The main features include a primer pair
      targeting a highly conserved region in the capsid and the addition of competing
      RNA that contains an internal deletion to provide a stringent internal control
      for quantification. It can be utilized to quantify RNA isolated from the four
      dengue virus serotypes but not RNA isolated from other flaviviruses, including
      Japanese encephalitis virus and hepatitis C virus, both prevalent in Asia. It can
      also be used to quantify dengue virus RNA isolated from the plasma of infected
      individuals. The sensitivity of the assay was estimated to be 10 to 50 copies of
      RNA per reaction, and twofold differences in virus titer are distinguishable.
      This assay is a convenient, sensitive, and accurate method for quantification and
      can be used to further understanding of the pathogenesis of dengue virus
      infection.

PMID- 10970376
TI  - Recent high incidence of fulminant hepatitis in Samara, Russia: molecular
      analysis of prevailing hepatitis B and D virus strains.
AB  - Until 1991, the Russian city of Samara was largely isolated from other parts of
      Russia and the rest of the world. Very recently, Samara has seen an alarming
      increase in the incidence of hepatitis. The proportion of fulminant cases is
      unusually high. We wanted to assess the roles of hepatitis B virus (HBV) and
      hepatitis D virus (HDV) in acute viral hepatitis in this region by analyzing the
      prevailing strains of both and by determining their genotypes and possible
      origin. Serum samples were screened for different serological markers and by PCR
      followed by direct sequencing. Of the 94 HBV-positive samples (80% of which were
      acute infections), 37 (39%) were also HDV positive. Sixty-seven percent of the
      patients had anti-HCV antibodies. Twenty-five percent of all patients in the
      study had fulminant hepatitis. Statistically significant sex differences were
      found among fulminant cases. For HBV, the core promoter sequences of 62 strains
      were determined and all but one were found to be of genotype D. None of these had
      any deletions. Only one strain, from a patient with fulminant fatal hepatitis,
      showed multiple mutations. The pre-S2 region sequences of 31 HBV strains were
      also compared. Phylogenetically, these fell into two distinct groups within
      genotype D, suggesting different origins. For HDV, part of the region encoding
      the delta-antigen was sequenced from four strains. All proved to be of genotype I
      and were similar to Far Eastern and Eastern European strains. The contribution of
      intravenous drug use to the sharp increase in viral hepatitis in this unique
      setting is discussed.

PMID- 10970377
TI  - Outbreak of vancomycin-resistant enterococci in a hospital in Gdask, Poland, due
      to horizontal transfer of different Tn1546-like transposon variants and clonal
      spread of several strains.
AB  - Twenty-two vancomycin-resistant enterococcal (VRE) isolates of the VanA phenotype
      (21 Enterococcus faecium isolates and 1 E. faecalis isolate), representative of a
      large outbreak that occurred in a hospital in Gdansk, Poland, were studied. All
      of the isolates demonstrated resistance to a wide variety of other antimicrobial
      agents in addition to glycopeptides. Several lines of evidence suggested that the
      outbreak most probably consisted of two epidemics that followed the independent
      introduction of VanA determinants into two separate hematological wards of the
      hospital. This hypothesis is supported by the fact that isolates recovered in
      these wards possessed two different polymorphs of the highly conserved DNA region
      encompassing the vanRSHAX genes and two distinct polymorph types of Tn1546-like
      transposons, which contain these genes. According to pulsed-field gel
      electrophoresis data, the outbreak in the adult hematology ward (HW) was highly
      polyclonal, which suggested a major role for the horizontal transmission of
      Tn1546-like elements among nonrelated strains of E. faecium and E. faecalis in
      this environment. On the other hand, the outbreak in the pediatric hematology
      ward (PHW) was most probably due to the clonal spread of two epidemic E. faecium
      strains, which had exchanged a plasmid carrying the Tn1546-like transposon.
      Restriction fragment length polymorphism studies of transposons and their
      insertion loci in plasmid DNA have suggested that numerous isolates from both HW
      and PHW contained two or more copies of Tn1546-like elements that underwent
      diversification due to various genetic modifications. The reported data
      demonstrated a very complex epidemiology of the first, and up to now the only,
      VanA VRE outbreak characterized in Poland.

PMID- 10970378
TI  - Distribution of Neisseria meningitidis serogroup B serosubtypes and serotypes
      circulating in the United States. The Active Bacterial Core Surveillance Team.
AB  - Because the Neisseria meningitidis serogroup B (NMSB) capsule is poorly
      immunogenic in humans, immunization strategies have focused on noncapsular
      antigens. Both PorA and to a lesser extent PorB are noncapsular protein antigens
      capable of inducing protective bactericidal antibodies, and vaccines based on the
      outer membrane protein (OMP) components of serogroup B meningococci have been
      shown to be effective in clinical trials. Multiple PorA antigens seem to be
      needed to prevent endemic meningococcal disease around the world, and a
      hexavalent PorA-based meningococcal vaccine has recently been developed in The
      Netherlands. To evaluate the distribution of NMSB PorA and PorB antigens in the
      United States, serosubtyping and serotyping were done on 444 NMSB strains
      isolated in the active surveillance areas of the United States (total population,
      32 million) during the period 1992 to 1998. A total of 244 strains were isolated
      from sporadic cases of meningococcal disease, and 200 strains were isolated from
      an epidemic in Oregon. A panel of 16 mouse monoclonal antibodies reactive with
      PorA and 15 monoclonal antibodies reactive with PorB were used. Among the NMSB
      isolates obtained from sporadic cases, the most prevalent serosubtypes were
      P1.7,16 (14.3%), P1.19,15 (9.8%), P1.7,1 (8.6%), P1.5,2 (7.8%), P1. 22a, 14
      (7.8%), and P1.14 (5.3%) and the most prevalent serotypes were 4,7 (27.5%), 15
      (16%), 14 (8.6%), 10 (6.1%), 1 (4.9%), and 2a (3.7%). A multivalent PorA-based
      OMP vaccine aimed at the six most prevalent serosubtypes could have targeted
      about half of the sporadic cases of NMSB disease that occurred between 1992 and
      1998 in the surveillance areas. Twenty serosubtypes would have had to be included
      in a multivalent vaccine to achieve 80% coverage of strains causing sporadic
      disease. The relatively large number of isolates that did not react with murine
      monoclonal antibodies indicates that DNA sequence-based variable region typing of
      NMSB will be necessary to provide precise information on the distribution and
      diversity of PorA antigens and correlation with nonserosubtypeable isolates. The
      high degree of variability observed in the PorA and PorB proteins of NMSB in the
      United States suggests that vaccine strategies not based on OMPs should be
      further investigated.

PMID- 10970379
TI  - Molecular taxonomy of the Trichophyton rubrum complex.
AB  - The validity of taxa around Trichophyton rubrum was evaluated by a combination of
      phenetic and molecular methods. Morphological and physiological features were
      compared to results of sequencing of the internal transcribed spacer region of
      the ribosomal operon, PCR fingerprinting, and amplified fragment length
      polymorphism analysis. The 15 species and varieties investigated (Trichophyton
      circonvolutum, Trichophyton fischeri, Trichophyton fluviomuniense, Trichophyton
      glabrum, Trichophyton gourvilii, Trichophyton kanei, Trichophyton kuryangei,
      Trichophyton megninii, Trichophyton pedis, Trichophyton raubitschekii,
      Trichophyton rodhaini, Trichophyton rubrum var. nigricans, Trichophyton
      soudanense, Trichophyton violaceum var. indicum, and Trichophyton yaoundei) were
      reclassified or synonymized as T. rubrum or T. violaceum.

PMID- 10970381
TI  - Use of the National Committee for Clinical Laboratory Standards guidelines for
      disk diffusion susceptibility testing in New York state laboratories.
AB  - Accurate antimicrobial susceptibility testing is vital for patient care and
      surveillance of emerging antimicrobial resistance. The National Committee for
      Clinical Laboratory Standards (NCCLS) outlines generally agreed upon guidelines
      for reliable and reproducible results. In January 1997 we surveyed 320
      laboratories participating in the New York State Clinical Evaluation Program for
      General Bacteriology proficiency testing. Our survey addressed compliance with
      NCCLS susceptibility testing guidelines for bacterial species designated a
      problem (Staphylococcus aureus and Enterococcus species) or fastidious
      (Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae)
      organism. Specifically, we assessed compliance with guidelines for inoculum
      preparation, medium choice, number of disks per plate, and incubation conditions
      for disk diffusion tests. We also included length of incubation for S. aureus and
      Enterococcus species. We found overall compliance with the five characteristics
      listed above in 80 of 153 responding laboratories (50.6%) for S. aureus and 72 of
      151 (47.7%) laboratories for Enterococcus species. The most common problem was an
      incubation time shortened to less than 24 h. Overall compliance with the first
      four characteristics was reported by 92 of 221 (41.6%) laboratories for S.
      pneumoniae, 49 of 163 (30.1%) laboratories for H. influenzae, and 11 of 77
      (14.3%) laboratories for N. gonorrhoeae. Laboratories varied from NCCLS
      guidelines by placing an excess number of disks per plate. Laboratories also
      reported using alternative media for Enterococcus species, N. gonorrhoeae, and H.
      influenzae. This study demonstrates a need for education among clinical
      laboratories to increase compliance with NCCLS guidelines.

PMID- 10970380
TI  - Detection of Giardia lamblia, Entamoeba histolytica/Entamoeba dispar, and
      Cryptosporidium parvum antigens in human fecal specimens using the triage
      parasite panel enzyme immunoassay.
AB  - The Triage parasite panel (BIOSITE Diagnostics, San Diego, Calif.) is a new
      qualitative enzyme immunoassay (EIA) panel for the detection of Giardia lamblia,
      Entamoeba histolytica/E. dispar, and Cryptosporidium parvum in fresh or fresh,
      frozen, unfixed human fecal specimens. By using specific antibodies, antigens
      specific for these organisms are captured and immobilized on a membrane. Panel
      performance was evaluated with known positive and negative stool specimens (a
      total of 444 specimens) that were tested by the standard ova and parasite (O&P)
      examination as the "gold standard," including staining with both trichrome and
      modified acid-fast stains. Specimens with discrepant results between the
      reference and Triage methods were retested by a different method, either EIA or
      immunofluorescence. A number of samples with discrepant results with the Triage
      device were confirmed to be true positives. After resolution of discrepant
      results, the number of positive specimens and the sensitivity and specificity
      results were as follows: for G. lamblia, 170, 95.9%, and 97.4%, respectively; for
      E. histolytica/E. dispar, 99, 96.0%, and 99.1%, respectively; and for C. parvum,
      60, 98.3%, and 99.7%, respectively. There was no cross-reactivity with other
      parasites found in stool specimens, including eight different protozoa (128
      challenges) and three different helminths (83 challenges). The ability to perform
      the complete O&P examination should remain an option for those patients with
      negative parasite panel results but who are still symptomatic.

PMID- 10970382
TI  - Analysis of 16S rRNA and 51-kilodalton antigen gene and transmission in mice of
      Ehrlichia risticii in virgulate trematodes from Elimia livescens snails in Ohio.
AB  - Operculate snails (the family Pleuroceridae: Elimia livescens) were collected
      between June and October 1998 from a river in central Ohio where repeated cases
      of Potomac horse fever (PHF) have occurred. Of collected snails, consistently 50
      to 80% carried a combination of cercariae and sporocysts of digenetic virgulate
      trematodes. The trematodes obtained from each snail were pooled and tested for
      Ehrlichia risticii, the agent of PHF, by nested PCR using primers specific to the
      16S rRNA gene. Out of a total of 209 trematode pools, 50 pools were found to be
      positive by PCR. The DNA sequence of the 16S rRNA gene identified in one
      trematode pool was identical to that of the type strain of E. risticii, and the
      sequence of the gene identified in another pool differed from that of the type
      strain by 1 nucleotide. Comparison of the deduced amino acid sequence of the
      partial 51-kDa antigen gene from various sources revealed that Maryland, Ohio
      (except Ohio 081), and Kentucky strains are in a cluster distinct from the
      sequences obtained from sources in California and Oregon. Ohio 081 was shown
      previously by antigenic composition analysis to be distinct from other groups.
      However, all sequences examined were not segregated according to their sources:
      horse blood or infected trematodes. E. risticii was found to be transmittable
      from trematodes to mice and was subsequently passaged from infected mice to
      additional mice, as determined by PCR analysis. Our findings suggest the
      evolution of E. risticii in the natural reservoir in separate geographic regions
      and persistent infection of trematode populations with E. risticii during summer
      and early fall. The study also suggests that the mouse can be used to isolate E.
      risticii from the infected trematode.

PMID- 10970383
TI  - In vitro susceptibility testing of filamentous fungi: comparison of Etest and
      reference microdilution methods for determining itraconazole MICs.
AB  - The performance of the Etest for itraconazole susceptibility testing of 50
      isolates of filamentous fungi was assessed in comparison with the National
      Committee for Clinical Laboratory Standards (NCCLS) proposed standard
      microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and
      MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were
      determined with RPMI agar containing 2% glucose and with Casitone agar and were
      read after incubation for 24 h (Aspergillus spp. and Rhizopus spp.) and 48 h (all
      species except Rhizopus spp.) at 35 degrees C. The isolates included Aspergillus
      flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Fusarium
      spp., Pseudallescheria boydii, Rhizopus spp., Paecilomyces variotii, and an
      Acremonium sp. Overall agreement between Etest and microdilution MICs was 96%
      with RPMI agar and 80% with Casitone agar. The agreement was 100% for all species
      except Rhizopus spp. (83%) and Paecilomyces varioti (0%) with RPMI agar. When
      Casitone agar was used, the agreement ranged from 50% with Rhizopus spp. to 100%
      with Fusarium spp., P. boydii, P. varioti, and an Acremonium sp. Notably, for
      Aspergillus spp., the agreement between itraconazole Etest MICs read at 24 h and
      reference microdilution MICs read at 48 h was 100% with both RPMI and Casitone
      agar. Both media supported the growth of all filamentous fungi tested. Where a
      discrepancy was observed between Etest and the reference method, the Etest MIC
      was generally higher. The Etest method using RPMI agar appears to be a useful
      method for determining itraconazole susceptibilities of Aspergillus spp. and
      other filamentous fungi.

PMID- 10970384
TI  - Characterization of the Mycobacterium bovis restriction fragment length
      polymorphism DNA probe pUCD and performance comparison with standard methods.
AB  - In this study, the newly described Mycobacterium bovis restriction fragment
      length polymorphism (RFLP) typing probe pUCD was characterized by sequence
      analysis and the previously observed polymorphic banding pattern was reproduced
      with a combination of three oligonucleotide probes in a single, mixed
      hybridization. In addition, the ability of pUCD to distinguish between 299 M.
      bovis isolates from the Republic of Ireland was assessed in relation to
      established methods and a statistical function for objective comparison of RFLP
      probes was derived. It was found that typing with pUCD alone produced greater
      discrimination between M. bovis isolates than typing with the commonly used
      mycobacterial DNA probes IS6110, PGRS, and DR and also by the spoligotyping
      technique. pUCD and DR in combination produced the highest level of
      discrimination while maintaining a high level of concordance with known
      epidemiological data relating to the samples. The reduction of pUCD to the level
      of oligonucleotides should in future allow pUCD and DR to be included together in
      a mixed hybridization, thus producing a high level of M. bovis strain type
      discrimination from a single round of RFLP analysis.

PMID- 10970386
TI  - Cutaneous infection caused by Cylindrocarpon lichenicola in a patient with acute
      myelogenous leukemia.
AB  - Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been
      associated with human disease. We report the first case of localized invasive
      cutaneous infection caused by this fungus in a 53-year-old male from the rural
      midwestern United States with relapsed acute myelogenous leukemia. On admission
      for induction chemotherapy, the patient was noted to have an abrasive laceration
      between the fourth and fifth metacarpophalangeal joints and on the dorsum of the
      right hand, which progressed to frank ulceration following chemotherapy. A biopsy
      provided an initial diagnosis of an invasive fungal infection consistent with
      aspergillosis based on the histopathological appearance of the mold in tissue.
      Multiple positive fungal cultures which were obtained from the biopsied tissue
      were subsequently identified by microscopic and macroscopic characteristics to be
      C. lichenicola. The infection resolved following marrow regeneration, aggressive
      debridement of the affected tissue, and treatment with amphotericin B. This case
      extends the conditions associated with invasive disease caused by C. lichenicola.

PMID- 10970385
TI  - Molecular characterization of rotavirus in Ireland: detection of novel strains
      circulating in the population.
AB  - A collection of three hundred thirty rotavirus-positive stool samples from
      children with diarrhea in the southern and eastern regions of Ireland between
      1997 and 1999 were submitted to the Molecular Diagnostics Unit of the Cork
      Institute of Technology, Cork, Ireland, for investigation. These strains were
      characterized by several methods, including polyacrylamide gel electropherotyping
      and G and P genotyping. A subset of the G types was confirmed by nucleic acid
      sequencing. The most prevalent types found in this collection included G1P[8] (n
      = 106; 32.1%), G2P[4] (n = 94; 28.5%), and G4P[8] (n = 37; 11.2%). Novel strains
      were also detected, including G1P[4] (n = 19; 5.8%), and G4P[4] (n = 2; 0.6%).
      Interestingly, mixed infections accounted for 18.8% (n = 62) of the total
      collection, with only 3% (n = 10) which were not G and/or P typeable.
      Significantly, six G8 and five G9 strains were identified as part of mixed
      infections. These strains have not previously been identified in Irish children,
      suggesting a greater diversity in rotavirus strains currently circulating in
      Ireland.

PMID- 10970387
TI  - Comparative fingerprinting analysis of Campylobacter jejuni subsp. jejuni strains
      by amplified-fragment length polymorphism genotyping.
AB  - Amplified-fragment length polymorphism (AFLP) analysis with the endonucleases
      BglII and MfeI was used to genotype 91 Campylobacter jejuni subsp. jejuni strains
      from outbreaks and sporadic cases. AFLP-generated fragments were labeled with
      fluorescent dye and separated by capillary electrophoresis. The software packages
      GeneScan and GelCompar II were used to calculate AFLP pattern similarities and to
      investigate phylogenetic relationships among the genotyped strains. The AFLP
      method was compared with two additional DNA-based typing methods, pulsed-field
      gel electrophoresis (PFGE) using SmaI and restriction fragment length
      polymorphism analysis on PCR products (PCR-RFLP) of the flaA and flaB genes. We
      found that AFLP analysis of C. jejuni strains is a rapid method that offers
      better discriminatory power than do both PFGE and PCR-RFLP. AFLP and, to a lesser
      extent, PCR-RFLP could differentiate strains within the same PFGE profiles, which
      also makes PCR-RFLP an alternative to PFGE. We were able to clearly distinguish 9
      of 10 recognized outbreaks by AFLP and to identify similarities among outbreak
      and sporadic strains. Therefore, AFLP is suitable for epidemiological
      surveillance of C. jejuni and will be an excellent tool for source identification
      in outbreak situations.

PMID- 10970388
TI  - Detection of human papillomavirus type 16 DNA in consecutive genital samples does
      not always represent persistent infection as determined by molecular variant
      analysis.
AB  - Persistent human papillomavirus (HPV) infection of the uterine cervix is a risk
      factor for progression to high-grade squamous intraepithelial lesions. Detection
      in consecutive genital samples of HPV-16 DNA, a frequently encountered HPV type,
      may represent persistent infection or reinfection. We undertook a study using PCR
      single-strand conformation polymorphism (SSCP) analysis and sequencing of PCR
      products (PCR-sequencing) to determine if consecutive HPV-16-positive samples
      contained the same HPV-16 variant. Fifty women (36 human immunodeficiency virus
      [HIV] seropositive, 14 HIV seronegative) had at least two consecutive genital
      specimens obtained at 6-month intervals that contained HPV-16 DNA as determined
      by a consensus L1 PCR assay. A total of 144 samples were amplified with two
      primer pairs for SSCP analysis of the entire long control region. Fifteen
      different SSCP patterns were identified in our population, while 22 variants were
      identified by PCR-sequencing. The most frequent SSCP pattern was found in 75
      (53%) samples from 27 (54%) women. The SSCP patterns obtained from consecutive
      specimens were identical for 46 (92%) of 50 women, suggesting persistent
      infection. Four women exhibited in consecutive specimens different HPV-16 SSCP
      patterns that were all confirmed by PCR-sequencing. The additional information on
      the nature of persistent infection provided by molecular variant analysis was
      useful for 6% of women, since three of the four women who did not have identical
      consecutive specimens would have been misclassified as having persistent HPV-16
      infection on the basis of HPV typing.

PMID- 10970389
TI  - Multilaboratory validation of rapid spot tests for identification of Escherichia
      coli.
AB  - To validate the accuracy of rapid tests for identification of Escherichia coli,
      five laboratories sequentially collected 1,064 fresh, clinically significant
      strains with core criteria of indole-positive, oxidase-negative, nonspreading
      organisms on sheep blood agar plates (BAP), having typical gram-negative rod
      plate morphology, defined as good growth on gram-negative rod-selective media. An
      algorithm using beta-hemolysis on BAP, lactose reaction on eosin-methylene blue
      or MacConkey agar, L-pyrrolidonyl-beta-naphthylamide (PYR), and 4
      methylumbelliferyl-beta-D-glucuronide (MUG) was evaluated. Identifications using
      the algorithm were compared to those obtained using commercial kit system
      identifications. One thousand strains were E. coli and 64 were not E. coli by kit
      identifications, which were supplemented with conventional biochemical testing of
      low probability profiles. Of the 1,064 isolates meeting the core criteria, 294
      were beta-hemolytic and did not require further testing to be identified as E.
      coli. None of the 64 non-E. coli strains were hemolytic, although other indole
      positive, lactose-negative species were found to be hemolytic when further
      strains were examined in a follow-up study. Of the remaining strains, 628 were
      identified as E. coli by a lactose-positive and PYR-negative reaction. For
      nonhemolytic, lactose-negative E. coli, PYR was not helpful, but a positive MUG
      reaction identified 65 of 78 isolates as E. coli. The remaining 13 E. coli
      strains required kit identifications. This scheme for E. coli identification
      misidentified three non-E. coli strains as E. coli, for an error rate of 0.3%. A
      total of 13 kit identifications, 657 PYR tests, and 113 MUG tests were needed to
      identify 1,000 E. coli strains with the algorithm. The use of this rapid system
      saves laboratory resources, provides timely identifications, and yields rare
      misidentifications.

PMID- 10970390
TI  - Characterization of Actinomyces isolates from infected root canals of teeth:
      description of Actinomyces radicidentis sp. nov.
AB  - Two strains of a previously undescribed Actinomyces-like bacterium were recovered
      in pure culture from infected root canals of teeth. Analysis by biochemical
      testing and polyacrylamide gel electrophoresis of whole-cell proteins indicated
      that the strains closely resembled each other phenotypically but were distinct
      from previously described Actinomyces and Arcanobacterium species. Comparative
      16S rRNA gene-sequencing studies showed the bacterium to be a hitherto unknown
      subline within a group of Actinomyces species which includes Actinomyces bovis,
      the type species of the genus. Based on phylogenetic and phenotypic evidence, we
      propose that the unknown bacterium isolated from human clinical specimens be
      classified as Actinomyces radicidentis sp. nov. The type strain of Actinomyces
      radicidentis is CCUG 36733.

PMID- 10970391
TI  - Comparison of Escherichia coli O157:H7 antigen detection in stool and broth
      cultures to that in sorbitol-MacConkey agar stool cultures.
AB  - We evaluated the Meridian IC-STAT direct fecal and broth culture antigen
      detection methods with samples from children infected with Escherichia coli
      O157:H7 and correlated the antigen detection results with the culture results.
      Stools of 16 children who had recently had stool cultures positive for this
      pathogen (population A) and 102 children with diarrhea of unknown cause
      (population B) were tested with the IC-STAT device (direct testing). Fecal broth
      cultures were also tested with this device (broth testing). The results were
      correlated to a standard of the combined yield from direct culture of stools on
      sorbitol-MacConkey (SMAC) agar and culture of broth on SMAC agar. Eleven (69%) of
      the population A stool specimens yielded E. coli O157:H7 when plated directly on
      SMAC agar. Two more specimens yielded this pathogen when the broth culture was
      similarly plated. Of these 13 stool specimens, 8 and 13 were positive by direct
      and broth testing (respective sensitivities, 62 and 100%). Compared to the
      sensitivity of a simultaneously performed SMAC agar culture, the sensitivity of
      direct testing was 73%. Three (3%) of the population B stool specimens contained
      E. coli O157:H7 on SMAC agar culture; one and three of these stool specimens were
      positive by direct and broth testing, respectively. The direct and broth IC-STAT
      tests were 100% specific with samples from children from population B. Direct IC
      STAT testing of stools is rapid, easily performed, and specific but is
      insufficiently sensitive to exclude the possibility of infection with E. coli
      O157:H7. Performing the IC-STAT test with a broth culture increases its
      sensitivity. However, attempts to recover E. coli O157:H7 by culture should not
      be abandoned but, rather, should be increased when the IC-STAT test result is
      positive.

PMID- 10970393
TI  - Whole-blood hemagglutination inhibition test for venereal disease research
      laboratory (VDRL) antibodies.
AB  - Nontreponemal antibody tests such as the Venereal Disease Research Laboratory
      (VDRL) test are carried out on serum and widely used as screening tests for
      syphilis. The aim of the present study was to develop a screening test for
      syphilis making use of whole blood and VDRL liposomes. Antibody to human red
      blood cells was conjugated to VDRL liposomes and reacted with a diluted sample of
      patient whole blood. A total of 951 samples were tested by the new test and the
      VDRL tube test. All 49 VDRL samples positive by the VDRL test showed inhibition
      of hemagglutination in the whole-blood test (sensitivity, 100%). Of 902 samples
      with negative results by the VDRL test, 901 caused hemagglutination when tested
      with the liposomes (specificity, 99.9%). The hemagglutination inhibition method
      tests for syphilis in a simple one-step procedure in which whole blood is added
      to a tube containing liposomes. The new test has potential for point-of-care
      testing in developing countries.

PMID- 10970392
TI  - Rapid extraction from and direct identification in clinical samples of
      methicillin-resistant staphylococci using the PCR.
AB  - Methicillin-resistant staphylococci (MRS) are one of the most common causes of
      nosocomial infections and bacteremia. Standard bacterial identification and
      susceptibility testing frequently require as long as 72 h to report results, and
      there may be difficulty in rapidly and accurately identifying methicillin
      resistance. The use of the PCR is a rapid and simple process for the
      amplification of target DNA sequences, which can be used to identify and test
      bacteria for antimicrobial resistance. However, many sample preparation methods
      are unsuitable for PCR utilization in the clinical laboratory because they either
      are not cost-effective, take too long to perform, or do not provide a
      satisfactory DNA template for PCR. Our goal was to provide same-day results to
      facilitate rapid diagnosis and therapy. In this report, we describe a rapid
      method for extraction of bacterial DNA directly from blood culture bottles that
      gave quality DNA for PCR in as little as 20 min. We compared this extraction
      method to the standard QIAGEN method for turnaround time (TAT), cost, purity, and
      use of template in PCR. Specific identification of MRS was determined using
      intragenic primer sets for bacterial and Staphylococcus 16S rRNA and mecA gene
      sequences. The PCR primer sets were validated with 416 isolates of staphylococci,
      including methicillin-resistant Staphylococcus aureus (n = 106), methicillin
      sensitive S. aureus (n = 134), and coagulase-negative Staphylococcus (n = 176).
      The total supply cost of our extraction method and PCR was $2.15 per sample with
      a result TAT of less than 4 h. The methods described herein represent a rapid and
      accurate DNA extraction and PCR-based identification system, which makes the
      system an ideal candidate for use under austere field conditions and one that may
      have utility in the clinical laboratory.

PMID- 10970394
TI  - Distribution of rotavirus VP7 serotypes and VP4 genotypes circulating in Sousse,
      Tunisia, from 1995 to 1999: emergence of natural human reassortants.
AB  - Rotavirus strains circulating in Sousse, Tunisia, between 1995 and 1999 were
      characterized antigenically by monoclonal antibodies to the VP6 subgroup and the
      VP7 serotype. The VP4 genotype was determined by reverse transcription-PCR, as
      were the strains with untyped VP7. Only 17% of 375 children were shedding
      rotavirus as determined by latex agglutination assay. Most rotavirus strains were
      G1P[8] (50%), followed by G4P[8] and G4P[6]. Reassortant G1P[4] strains emerged
      in Sousse during the 1998-1999 season.

PMID- 10970395
TI  - Genotyping of the capsule gene cluster (cps) in nontypeable group B streptococci
      reveals two major cps allelic variants of serotypes III and VII.
AB  - Forty group B Streptococcus (GBS) isolates obtained from Europe and the United
      States previously reported to be nontypeable (NT) by capsule serotype
      determination were subjected to buoyant density gradient centrifugation. From
      nearly half of the isolates capsule-expressing variants could be selected. For
      characterization of the remaining NT-GBS isolates, the capsule operon (cps) was
      amplified by the long-fragment PCR technique and compared by restriction fragment
      length polymorphism (RFLP) analysis. The patterns from serotype reference
      isolates (n = 32) were first determined and used as a comparison matrix for the
      NT-GBS isolates. Using two restriction enzymes, SduI and AvaII, cluster analysis
      revealed a high degree of similarity within serotypes but less than 88%
      similarity between serotypes. However, serotypes III and VII were each split in
      two distant RFLP clusters, which were designated III(1) and III(2) and VII(1) and
      VII(2), respectively. Among the isolates that remained NT after repeated Percoll
      gradient selections, two insertional mutants were revealed. Both were found in
      blood isolates and harbored insertion sequence (IS) elements within cpsD: one
      harbored IS1548, and the other harbored IS861. All other NT-GBS isolates could,
      by cluster analysis, be referred to different serotypes by comparison to the RFLP
      reference matrix. In pulsed-field gel electrophoresis of SmaI-restricted
      chromosomal DNA, patterns from allelic type 1 and 2 isolates were essentially
      distributed in separate clusters in serotypes III and VII. A covariation with
      insertion sequence IS1548 in the hylB gene was suggested for serotype III, since
      allelic type III(1) harboring IS1548 in hylB, clustered separately. The variation
      in serotype VII was not dependent on the presence of IS1548, which was not
      detected at any position in the type VII chromosome.

PMID- 10970396
TI  - Automated 5' nuclease PCR assay for identification of Salmonella enterica.
AB  - A simple and ready-to-go test based on a 5' nuclease (TaqMan) PCR technique was
      developed for identification of presumptive Salmonella enterica isolates. The
      results were compared with those of conventional methods. The TaqMan assay was
      evaluated for its ability to accurately detect 210 S. enterica isolates,
      including 100 problematic "rough" isolates. An internal positive control was
      designed to use the same Salmonella primers for amplification of a spiked
      nonrelevant template (116 bp) in the sample tube. The PCR test correctly
      identified all the Salmonella strains by resulting in positive end-point
      fluorescence (FAM) signals for the samples and positive control (TET) signals
      (relative sensitivity [DeltaRn], >0. 6). The diagnostic specificity of the method
      was assessed using 120 non-Salmonella strains, which all resulted in negative FAM
      signals (DeltaRn, < or =0.5). All 100 rough Salmonella strains tested resulted in
      positive FAM and TET signals. In addition, it was found that the complete PCR
      mixture, predispensed in microwell plates, could be stored for up to 3 months at 
      20 degrees C. Thus, the diagnostic TaqMan assay developed can be a useful and
      simple alternative method for identification of Salmonella, particularly in large
      reference laboratories.

PMID- 10970397
TI  - Differences in surface-exposed antigen expression between Helicobacter pylori
      strains isolated from duodenal ulcer patients and from asymptomatic subjects.
AB  - We have analyzed possible qualitative and quantitative differences in antigen
      expression between Helicobacter pylori strains isolated from the antrum and
      different locations in the duodenum of 21 duodenal ulcer (DU) patients and 20
      asymptomatic subjects (AS) by enzyme-linked immunosorbent assay (ELISA) and
      inhibition ELISA. Almost all antral and duodenal strains grown in vitro expressed
      the N-acetyl-neuroaminyllactose-binding hemagglutinin, flagellins (subunits FlaA
      and FlaB), urease, a 26-kDa protein, and a neutrophil-activating protein. In 75%
      of both the DU patients and the AS, antral H. pylori strains expressed either the
      blood group antigen Lewis y (Le(y)) alone or together with the Le(x) antigen.
      However, duodenal H. pylori strains of DU patients expressed Le(y) antigen more
      frequently than corresponding strains of AS (P < 0.05). Presence of Le(y) on H.
      pylori was related to the degree of active duodenitis (P < 0.05). Duodenal H.
      pylori strains isolated from AS were significantly more often Lewis nontypeable
      than duodenal strains of DU patients (P < 0.01). Presence of H. pylori blood
      group antigen-binding adhesin (BabA) was significantly higher on both antral and
      duodenal strains isolated from DU patients than on corresponding strains isolated
      from AS (P < 0.05). BabA-positive duodenal H. pylori strains isolated from DU
      patients were associated with active duodenitis more frequently than
      corresponding strains isolated from AS (P < 0.01). Infection with H. pylori
      strains positive for Le(y) and BabA in the duodenum is associated with
      development of duodenal ulcer formation.

PMID- 10970398
TI  - Detection and quantitation of hepatitis C virus RNA in feces of chronically
      infected individuals.
AB  - Hepatitis C virus (HCV) RNA was detected and quantified in human fecal specimens
      with the Roche COBAS AMPLICOR system adapted by us for fecal specimens. HCV RNA
      could be detected in the feces of four of six (67%) patients chronically infected
      with HCV, with loads up to about 2.8 x 10(5) copies/ml of feces. The same HCV
      genotypes were observed in feces and plasma as determined by direct sequencing of
      the 5' untranslated region.

PMID- 10970399
TI  - Hospital-based evaluation of two rapid human immunodeficiency virus antibody
      screening tests.
AB  - Two rapid human immunodeficiency virus (HIV) screening assays, HIV TRI-DOT and
      HIV-SPOT were compared with standard enzyme-linked immunosorbent assays according
      to a testing algorithm. Sensitivities and specificities in the real-time
      evaluation were 99.5 and 99.9% for TRI-DOT and 98.2 and 99.7% for HIV-SPOT,
      respectively. These two tests are suitable for use where facilities and
      laboratory expertise are limited.

PMID- 10970400
TI  - Seroepidemiological survey of infection by feline leukemia virus and
      immunodeficiency virus in Madrid and correlation with some clinical aspects.
AB  - A study of 180 healthy cats found that 15.6% were feline leukemia virus (FeLV)
      positive, 8.3% were feline immunodeficiency virus (FIV) positive, and 1.1% were
      FIV and FeLV positive, which corresponded to 30.4, 13.8, and 2.6, of 115 cats
      with FIV- and FeLV-related symptoms, respectively. Differences were seen in the
      sexes and ages of the populations studied. Anemia, leukopenia, and lymphopenia
      were the most frequent hematological abnormalities in infected cats.

PMID- 10970401
TI  - Hepatitis C virus core mutations reduce the sensitivity of a fluorescence enzyme
      immunoassay.
AB  - Four of 107 samples obtained from hepatitis C virus (HCV) carriers showed lower
      HCV core antigen levels in a fluorescence enzyme immunoassay (FEIA) than expected
      from corresponding HCV RNA levels. Nucleotide sequencing revealed a mutation in
      the HCV core region (Thr49Pro) that appears to have reduced the FEIA sensitivity.

PMID- 10970402
TI  - Use of coagulase gene (coa) repeat region nucleotide sequences for typing of
      methicillin-resistant Staphylococcus aureus strains.
AB  - Coagulase gene (coa) short sequence repeat region sequencing was used to measure
      relatedness among a collection of temporally and geographically diverse
      methicillin-resistant Staphylococcus aureus isolates. The results show that coa
      polymorphism is free of strong selective pressure and has a low index of
      variation that may be useful for long-term epidemiological investigations. coa
      typing is a useful addition to spa typing for analysis of S. aureus, including
      methicillin-resistant strains.

PMID- 10970403
TI  - Quality control limits for broth microdilution susceptibility tests of ten
      antifungal agents.
AB  - Broth microdilution susceptibility tests of Candida species have now been
      standardized by the National Committee for Clinical Laboratory Standards (NCCLS).
      An eight-laboratory collaborative study was carried out in order to document
      reproducibility of tests of Candida parapsilosis ATCC 22019 and Candida krusei
      ATCC 6258 by the NCCLS method. Replicate broth microdilution tests were used to
      define control limits for 24- and 48-h MICs of amphotericin B, flucytosine,
      fluconazole, voriconazole, ketoconazole, itraconazole, caspofungin (MK 0991),
      ravuconazole (BMS 207147), posaconazole (SCH 56592), and LY 303366.

PMID- 10970404
TI  - Mixed infection caused by two species of Fusarium in a human immunodeficiency
      virus-positive patient.
AB  - We report on a case of mixed infection caused by two species of Fusarium in a
      human immunodeficiency virus-positive patient with lymphoma who was neutropenic
      due to chemotherapy. The patient showed the typical signs of a disseminated
      fusarial infection, with Fusarium solani isolated from skin lesions and F.
      verticillioides isolated from blood. The report discusses how difficult it is to
      make an accurate diagnosis when an immunosuppressed patient is infected with more
      than one fungal species, especially when the species are morphologically very
      similar.

PMID- 10970405
TI  - Analysis of genetic heterogeneity in Chlamydia trachomatis clinical isolates of
      serovars D, E, and F by amplified fragment length polymorphism.
AB  - Amplified fragment length polymorphism (AFLP) fingerprinting of clinical isolates
      of Chlamydia trachomatis serovars D, E, and F showed a low percentage of genetic
      heterogeneity, but clear differences were found. Isolates from index patients and
      partners had identical AFLP patterns and AFLP markers. Characterization of these
      AFLP markers could give more insight into the differences in virulence and
      clinical course of C. trachomatis infections.

PMID- 10970406
TI  - Heterogeneity of influenza B virus strains in one epidemic season differentiated
      by monoclonal antibodies and nucleotide sequences.
AB  - Seventy-three B/Victoria group strains isolated in the 1996-1997 influenza season
      were divided into three groups according to the degree of reactivity to
      monoclonal antibody 8E6. Analysis of nucleotide sequences of the HA1 region
      clarified that single amino acid substitutions were responsible for the
      difference in reactivity to 8E6.

PMID- 10970407
TI  - Cattle can be a reservoir of sorbitol-fermenting shiga toxin-producing
      Escherichia coli O157:H(-) strains and a source of human diseases.
AB  - Using the immunomagnetic separation procedure, we isolated sorbitol-fermenting
      (SF) Shiga toxin-producing Escherichia coli (STEC) O157:H(-) strains from two
      patients, one with hemolytic-uremic syndrome and the other with diarrhea, and
      from a dairy cow epidemiologically associated with the patients. The phenotypic
      and genotypic characteristics of all isolates were identical or closely related.
      Moreover, the bovine isolate showed a clonal relatedness to SF STEC O157:H(-)
      strains isolated from patients in Germany and the Czech Republic from 1988 to
      1998. This is the first evidence that cattle can be a reservoir of SF STEC
      O157:H(-) and a source of human diseases.

PMID- 10970408
TI  - Quantitative, competitive PCR analysis of porcine circovirus DNA in serum from
      pigs with postweaning multisystemic wasting syndrome.
AB  - A competitive PCR (cPCR) assay was developed for monitoring porcine circovirus
      (PCV) DNA in serum samples from piglets. The cPCR was based on competitive
      coamplification of a 502- or 506-bp region of the PCV type 1 (PCV1) or PCV2 ORF2,
      respectively, with a known concentration of competitor DNA, which produced a 761-
      or 765-bp fragment, respectively. The cPCR was validated by quantification of a
      known amount of PCV wild-type plasmids. We also used this technique to determine
      PCV genome copy numbers in infected cells. Furthermore, we measured PCV DNA loads
      in clinical samples. More than 50% of clinically healthy piglets could harbor
      both types of PCV. While PCV1 was detected in only 3 of 16 pigs with postweaning
      multisystemic wasting syndrome (PMWS), all the sick piglets contained PCV2. A
      comparison of the PCV2 DNA loads of healthy and sick animals revealed a
      significant difference, indicating that the development of PMWS may require a
      certain amount of PCV2.

PMID- 10970409
TI  - PCR for diagnosis of paracoccidioidomycosis.
AB  - A PCR assay based on oligonucleotide primers derived from the sequence of the
      gene coding for the 43,000-Da (gp43) antigen was developed to detect
      Paracoccidioides brasiliensis DNA in sputa. In the standardized conditions, it
      could detect 10 cells/ml of sputum, providing sufficient accuracy to be useful
      for diagnosis of paracoccidioidomycosis.

PMID- 10970410
TI  - Identification and type distribution of astroviruses among children with
      gastroenteritis in Colombia and Venezuela.
AB  - Astrovirus infections were detected by enzyme immunoassay in 12 (5%) of 251 stool
      samples from children with gastroenteritis from Bogota, Colombia. In addition,
      astroviruses were detected by reverse transcription-PCR in 3 (10%) of 29 stool
      samples negative for other enteric pathogens collected in Caracas, Venezuela,
      from children with gastroenteritis. Astrovirus type 1 was the most frequently
      detected virus.

PMID- 10970411
TI  - Identification of DT104 and U302 phage types among Salmonella enterica serotype
      typhimurium isolates by PCR.
AB  - A DNA sequence was identified in isolates of Salmonella enterica serotype
      Typhimurium definitive type 104 (DT104). The PCR amplification of an internal
      segment of this sequence identified DT104 and the closely related U302 phage type
      among 146 isolates of S. enterica serotype Typhimurium tested, thus providing a
      tool for rapid identification of DT104 and related isolates.

PMID- 10970412
TI  - Characterization of Neisseria gonorrhoeae strains with decreased susceptibility
      to fluoroquinolones isolated in Greece from 1996 to 1999.
AB  - Of the 331 Neisseria gonorrhoeae strains isolated in Greece from 1996 to 1999, 39
      (11.8%) exhibited decreased susceptibility to quinolones due to gyrA and parC
      mutations. Conventional typing and pulsed-field gel electrophoresis showed that
      34 of these isolates were clonally related. Epidemiological data indicated that
      the epidemic clone was sustained in a group of high-frequency transmitters.

PMID- 10970413
TI  - Molecular cloning, expression, and antigenicity of Seto virus belonging to
      genogroup I Norwalk-like viruses.
AB  - The viral capsid protein of the Seto virus (SeV), a Japanese strain of genogroup
      I Norwalk-like viruses (NLVs), was expressed as virus-like particles using a
      baculovirus expression system. An antigen detection enzyme-linked immunosorbent
      assay based on hyperimmune antisera to recombinant SeV was highly specific to
      homologous SeV-like strains but not heterologous strains in stools, allowing us
      type-specific detection of NLVs.

PMID- 10970414
TI  - Fecal excretion of Salmonella enterica serovar typhimurium following a food-borne
      outbreak.
AB  - Fecal excretion of Salmonella enterica serovar Typhimurium organisms was observed
      in patients and in people not showing symptoms who were involved in an outbreak
      of food-borne infection with this organism. Excretion of organisms was prolonged
      in the patients who were given antimicrobial drugs compared with those who were
      not. The isolates were indistinguishable by their pulsed-field gel
      electrophoresis patterns and biotyping from the strain recovered from the roast
      pork that had been consumed by all of the people. This indicates that these
      isolates obtained from the infected people had originated in the contaminated
      pork.

PMID- 10970415
TI  - Genetic classification of "Rickettsia heilongjiangii" and "Rickettsia hulinii,"
      two Chinese spotted fever group rickettsiae.
AB  - To determine the phylogenetic position of two new rickettsial strains isolated
      from ticks in China, 16S ribosomal DNA, gltA, and ompA (apart from the tandem
      repeat units) genes were amplified by PCR and sequenced. The phylogenetic
      relationships between these strains and other rickettsiae were inferred from the
      comparison of sequences of the three genes by the parsimony, neighbor-joining,
      and maximum-likelihood methods. The results demonstrated that the 054 strain, a
      rickettsia pathogenic in humans, and the HL-93 strain were related and clustered
      together with Rickettsia japonica. Significant statistical bootstrap values (100
      and 92%) supported the nodes in this cluster. Based on previous genotypic and
      antigenic data and the phylogenetic analysis presented here, the 054 and HL-93
      strains should be considered as new species, and we formally propose that they be
      named "Rickettsia heilongjiangii" and "Rickettsia hulinii," respectively.

PMID- 10970416
TI  - Comparison of a ligase chain reaction-based assay and cell culture for detection
      of pharyngeal carriage of Chlamydia trachomatis.
AB  - In 264 genitourinary medicine clinic attenders reporting recent fellatio, the
      prevalence of pharyngeal Chlamydia trachomatis determined by an expanded standard
      including cell culture and two in-house PCR tests was 1.5% in 194 women and zero
      in 70 men. The ligase chain reaction (Abbott LCx) had a specificity of 99.2% and
      a positive predictive value of 60%.

PMID- 10970417
TI  - Pseudo-outbreak of imipenem-resistant Acinetobacter baumannii resulting from
      false susceptibility testing by a rapid automated system.
AB  - Introduction of the Vitek GNS-506 susceptibility testing cards in the
      Hippokration General Hospital, Thessaloniki, Greece, resulted in an apparently
      high prevalence of imipenem-resistant Acinetobacter baumannii. When 35 of these
      isolates were further tested by disk diffusion, broth microdilution, and agar
      dilution assays, 32 were imipenem sensitive by all tests and three were sensitive
      or intermediate, depending on the method. The pseudoresistant acinetobacters did
      not form a genetically homogeneous group. It is suggested that the detection of
      imipenem-resistant A. baumannii isolates by this system should be confirmed by an
      additional susceptibility test.

PMID- 10970418
TI  - Comparison of rapid centrifugation assay with conventional tissue culture method
      for isolation of dengue 2 virus in C6/36-HT cells.
AB  - A rapid centrifugation assay was compared with conventional tube cell culture for
      dengue virus isolation in both sera and autopsy samples from dengue and dengue
      hemorrhagic fever/dengue shock syndrome fatal cases. The rapid centrifugation
      assay allowed isolation of virus from 16.6% more samples than the conventional
      method, and it shortened the time for dengue virus detection. Finally, it allowed
      the isolation of dengue 2 virus in 42.8% of tissue samples from five fatal cases.
      Our results suggest that the rapid centrifugation assay may be useful for
      detection of dengue virus in clinical specimens.

PMID- 10970419
TI  - Continuous ambulatory peritoneal dialysis peritonitis due to Enterococcus
      cecorum.
AB  - Enterococcus cecorum was isolated as the etiologic agent of a continuous
      ambulatory peritoneal dialysis peritonitis episode in an alcoholic patient. To
      date, this is only the third infection due to this bacterium, found in the
      intestinal tract of many domestic animals, that has been reported in humans.

PMID- 10970420
TI  - Brevibacterium casei sepsis in an 18-year-old female with AIDS.
AB  - Brevibacterium sp. was isolated from the blood of an acutely ill 18-year-old
      female with AIDS. The isolate was identified as Brevibacterium casei by use of
      carbohydrate assimilation tests. Treatment was successful with intravenously
      administered ciprofloxacin. To our knowledge, this is the first report of sepsis
      caused by B. casei in a human immunodeficiency virus-infected patient.

PMID- 10970421
TI  - Identification of Mycobacterium neoaurum isolated from a neutropenic patient with
      catheter-related bacteremia by 16S rRNA sequencing.
AB  - A rapidly growing pigmented mycobacterial strain with an ambiguous biochemical
      profile was isolated from the blood culture taken through the Hickman catheter of
      a 9-year-old girl with acute lymphoblastic leukemia. Whole-cell fatty acid
      analysis showed that the best match profile was that of Mycobacterium aurum, but
      the similarity index was only 0.217, meaning that there were no good matches
      between the isolate and the organisms in the database of the Microbial
      Identification System. The 16S rRNA gene of the mycobacterial strain was
      amplified, agarose gel purified, and sequenced. There were 44 base differences
      between the gene sequence of the isolate and that of M. aurum but only one base
      difference between the sequence of the isolate and that of Mycobacterium
      neoaurum, showing that the isolate was indeed a strain of M. neoaurum by using
      this "gold standard." This represents the first case of M. neoaurum infection
      documented by 16S rRNA sequencing.

PMID- 10970422
TI  - A cytotoxin-producing strain of Vibrio cholerae non-O1, non-O139 as a cause of
      cholera and bacteremia after consumption of raw clams.
AB  - We report a case of a cholera-like gastroenteritis subsequent with bacteremia in
      a healthy man following consumption of raw clams. Although we failed to recover
      the organism from the patient's stool culture, his blood culture was positive for
      a non-cholera toxin-producing yet cytotoxin-producing non-O1 and non-O139 Vibrio
      cholerae.

PMID- 10970423
TI  - Differential modulation of N-type 1B and P/Q-type 1A calcium channels by
      different G protein subunit isoforms.
AB  - Using transient calcium phosphate transfection into the human embryonic kidney
      tsa-201 cell line and subsequent whole-cell patch-clamp protocols, we examined
      the tonic modulation of cloned N- and P/Q-type calcium channels by five different
      G protein beta subunits via strong depolarizing voltage prepulses. For N- and P/Q
      type channels, the magnitude of inhibition was dependent on the Gbeta subtype co
      expressed. Both the absolute and relative magnitudes of Gbeta subunit-induced
      inhibition of P/Q-type channels differed from those observed with the N-type
      channel. For each calcium channel subtype, kinetics of both the prepulse-mediated
      recovery from inhibition and the re-inhibition following the prepulse were
      examined for each of the Gbeta subunits by varying either the duration between
      the pre- and the test pulse or the length of the prepulse. For each channel
      subtype, we observed a differential Gbeta subunit rank order with regard to the
      rates of re-inhibition and recovery from inhibition. On average, P/Q-type
      channels exhibited more rapid rates of recovery from inhibition than those
      observed with N-type channels. Different Gbeta subtypes mediated different
      degrees of slowing of activation kinetics. The differential modulation of P/Q-
      and N-type channels by various Gbeta subtypes may provide a mechanism for fine
      tuning the amount of calcium entering the presynaptic nerve termini.

PMID- 10970424
TI  - Coupling between serotoninergic and noradrenergic neurones and gamma-motoneurones
      in the cat.
AB  - Noradrenaline is known to suppress transmission from group II muscle afferents
      when locally applied to gamma-motoneurones, and serotonin (5-HT) facilitates the
      transmission. The purpose of this investigation was to search for evidence of
      monoaminergic innervation of gamma-motoneurones. Eight gamma-motoneurones were
      labelled with rhodamine-dextran, and 50 micrometer thick sagittal sections of the
      spinal cord containing them were exposed to antibodies against dopamine beta
      hydroxylase (DBH) and 5-HT. All the cells were directly and/or indirectly excited
      by muscle group II afferents from the muscle they innervated and/or other
      muscles. Appositions between monoaminergic fibres and the labelled somata and
      dendrites were located with three-colour confocal laser scanning microscopy by
      examining series of optical sections at 1 or 0.5 micrometer intervals. DBH and 5
      HT varicosities formed appositions with the somata and dendrites of all the gamma
      motoneurones. The mean packing densities for 5-HT (1.12 +/- 0.11 appositions per
      100 micrometer(2) for somata and 0.91 +/- 0.07 per 100 micrometer(2) for
      dendrites) were similar to the densities of contacts reported for alpha
      motoneurones. Monoaminergic varicosities in apposition to dendrites greatly
      outnumbered those on the somata. The density of DBH appositions was consistently
      lower - corresponding means were 53% and 62% of those for 5-HT on the somata and
      dendrites, respectively. It is concluded from an analysis of the distribution and
      density of varicosities in apposition to the gamma-motoneurones compared with the
      density in the immediate surround of the dendrites that there is indeed both a
      serotoninergic and noradrenergic innervation of gamma-motoneurones.

PMID- 10970426
TI  - Whole-cell and single channel monovalent cation currents through the novel rabbit
      epithelial Ca2+ channel ECaC.
AB  - This study describes properties of monovalent cation currents through ECaC, a
      recently cloned epithelial Ca2+-permeable channel from rabbit. The kinetics of
      currents through ECaC was strongly modulated by divalent cations. Currents were
      inhibited in the presence of extracellular Ca2+. They showed an initial voltage
      dependent decay in the presence of mM Mg2+ at hyperpolarizing steps in Ca2+-free
      solutions, which represents a voltage-dependent Mg2+ block through binding of
      Mg2+ to a site localized in the electrical field of the membrane (delta = 0.31)
      and a voltage-dependent binding constant (at 0 mV 3.1 mM Ca2+, obtained from a
      Woodhull type analysis). Currents were only stable in the absence of divalent
      cations and showed under these conditions a small time- and voltage-dependent
      component of activation. Single channel currents in cell-attached and inside-out
      patches had a conductance of 77.5 +/- 4.9 pS (n = 11) and reversed at +14.8 +/-
      1. 6 11imV81i (n = 9) in the absence of divalent cations. The permeation sequence
      for monovalent cations through ECaC was Na+ > Li+ > K+ > Cs+ > NMDG+ which is
      identical to the Eisenmann sequence X for a strong field-strength binding site.
      It is concluded that the permeation profile of ECaC for monovalent cations
      suggests a strong field-strength binding site that may be involved in Ca2+
      permeation and Mg2+ block.

PMID- 10970425
TI  - Single-channel analysis of an NMDA receptor possessing a mutation in the region
      of the glutamate binding site.
AB  - Recombinant NR1a/NR2A(T671A) N-methyl-D-aspartate (NMDA) receptor-channels, which
      carry a point mutation in the putative glutamate binding site that reduces
      glutamate potency by around 1000-fold, have been expressed in Xenopus laevis
      oocytes and their single-channel properties examined using patch-clamp recording
      techniques. Shut time distributions of channel activity were fitted with a
      mixture of five exponential components. The first three components in each
      distribution were considered to occur within a channel activation as they
      exhibited little or no dependence on agonist concentration. Bursts of single
      channel openings were defined by a critical gap length with a mean of 5.65 +/-
      0.37 ms. Shut intervals with a duration longer than this value were considered to
      occur between separate bursts of channel openings. Distributions of the lengths
      of bursts of openings were fitted with a mixture of four exponential components.
      The longest two components carried the majority of the charge transfer in the
      channel recordings and had means of 7.71 +/- 1.1 and 37.7 +/- 4.3 ms. The overall
      probability of a channel being open during a burst was high (mean 0.92 +/- 0.01).
      Brief concentration jumps (1 ms) of 10 mM glutamate were applied to outside-out
      patches so that a comparison between the macroscopic current relaxation and
      steady-state single-channel activity evoked by glutamate could be made. The decay
      of such macroscopic currents was fitted with a single exponential component with
      a mean of 32.0 +/- 3.53 ms. The good agreement between macroscopic current decay
      following brief agonist exposure and the value for the slowest component of the
      burst length distribution suggests that the bursts of openings that we identified
      in steady-state recordings represent individual activations of recombinant
      NR1a/NR2A(T671A) NMDA receptor-channels. A new way of displaying geometric
      distributions is suggested, and the utility of a modified definition of the
      'probability of being open within a burst' is discussed. The single-channel data
      that we present in this paper support further the idea that the point mutation
      T671A in the NR2A NMDA receptor subunit affects mainly the ability of glutamate
      to remain bound to these channels.

PMID- 10970427
TI  - Distinct mechanisms for activation of Cl- and K+ currents by Ca2+ from different
      sources in mouse sympathetic neurones.
AB  - We have investigated the roles of different voltage-dependent Ca2+ channels in
      the activation of the Cl- and K+ channels responsible for the afterdepolarization
      (ADP) and slow afterhyperpolarization (AHP) in sympathetic neurones of the
      isolated mouse superior cervical ganglion in vitro. The ADP and its associated
      Ca2+-activated Cl- current were markedly decreased by omega-agatoxin IVA (40-200
      nM) and nifedipine (1-10 microM), but not by omega-conotoxin GVIA (300 nM). In
      contrast, the AHP and the apamin-sensitive Ca2+-activated K+ current that
      underlies this potential were blocked by omega-conotoxin GVIA, but were not
      affected by omega-agatoxin IVA and were only slightly reduced by nifedipine.
      Ryanodine (20 microM) reduced the Ca2+-activated Cl- current following an action
      potential by 75% but on average did not affect the Ca2+-activated K+ current.
      Evidence that R-type channels provide a proportion of the Ca2+ activating both
      types of Ca2+-dependent channel was obtained. We conclude that Ca2+ entering
      through L- and P-type Ca2+ channels preferentially activates the Cl- current
      responsible for the ADP in mouse sympathetic neurones, predominantly via Ca2+
      induced Ca2+ release, whereas the Ca2+ that activates the K+ channels responsible
      for the AHP enters predominantly through N-type channels. The data can be
      explained by the selective association of each type of Ca2+ channel with
      particular intracellular mechanisms for activating other membrane channels, one
      indirect and the other direct, probably located at discrete sites on the soma and
      dendrites.

PMID- 10970429
TI  - Molecular determinants of Ca2+-dependent K+ channel function in rat dorsal vagal
      neurones.
AB  - Using in situ hybridisation histochemistry in combination with patch-clamp
      recordings and specific pharmacological tools, the molecular nature of the
      channels underlying Ca2+-dependent K+ currents was determined in dorsal vagal
      neurones (DVNs) of rat brainstem slices. In situ hybridisation analysis at
      cellular resolution revealed the presence of 'big'-conductance Ca2+- and voltage
      activated K+ (BK) channel alpha-subunit mRNA, and of only one 'small'-conductance
      Ca2+-activated K+ (SK) channel subunit transcript, SK3, at very high levels in
      DVNs. By contrast, SK1 and SK2 mRNAs were below the threshold limit of detection.
      The SK channel-mediated after-hyperpolarising current (IAHP) was blocked by
      apamin with a half-maximal inhibitory concentration of approximately 2.2 nM. This
      is consistent with homomultimeric SK3 channels mediating IAHP in DVNs. IAHP was
      also blocked by scyllatoxin (20-30 nM) and curare (100-200 microM). Application
      of apamin (100 nM) or scyllatoxin (20 nM) invariably caused a substantial
      increase to 146.1 +/- 10.4 and 181.8 +/- 12.9 % of control, respectively, in the
      spontaneous firing rate of DVNs. Action potential duration was not affected by
      these SK channel blockers. The selective BK channel blocker iberiotoxin (50 nM)
      increased action potential duration by 22.5 +/- 7.3 %, as did low concentrations
      of tetraethylammonium (0.5 mM; 99.3 +/- 16.4 %) and the Ca2+ channel blocker Cd2+
      (100 microM; 49.5 +/- 20.9 %). BK channel blockade did not significantly affect
      the firing rate of DVNs. These results allow us to establish a tight correlation
      between the properties of cloned and native BK and SK channels, and to achieve an
      understanding, at the molecular level, of their role in regulating the
      spontaneous firing frequency and in shaping single action potentials of central
      neurones.

PMID- 10970430
TI  - Electrophysiological and morphological characteristics of three subtypes of rat
      globus pallidus neurone in vitro.
AB  - Neurones of the globus pallidus (GP) have been classified into three subgroups
      based on the visual inspection of current clamp electrophysiological properties
      and morphology of biocytin-filled neurones. Type A neurones (132/208; 63 %) were
      identified by the presence of the time- and voltage-dependent inward rectifier
      (Ih) and the low-threshold calcium current (It) giving rise to anodal break
      depolarisations. These cells were quiescent or fired regular spontaneous action
      potentials followed by biphasic AHPs. Current injection evoked regular activity
      up to maximum firing frequency of 350 Hz followed by moderate spike frequency
      adaptation. The somata of type A cells were variable in shape (20 x 12
      micrometer) while their dendrites were highly varicose. Type B neurones (66/208;
      32 %) exhibited neither Ih nor rebound depolarisations and only a fast monophasic
      AHP. These cells were spontaneously active while current injection induced
      irregular patterns of action potential firing up to a frequency of 440 Hz with
      weak spike frequency adaptation. Morphologically, these cells were the smallest
      encountered (15 x 10 micrometer), oval in shape with restricted varicose
      dendritic arborisations. Type C neurones were much rarer (10/208; 5 %). They were
      identified by the absence of Ih and rebound depolarisations, but did possess a
      prolonged biphasic AHP. They displayed large A-like potassium currents and ramp
      like depolarisations in response to step current injections, which induced firing
      up to a maximum firing frequency of 310 Hz. These cells were the largest observed
      (27 x 15 micrometer) with extensive dendritic branching. These results confirm
      neuronal heterogeneity in the adult rodent GP. The driven activity and population
      percentage of the three subtypes correlates well with the in vivo studies (Kita &
      Kitai, 1991). Type A cells appear to correspond to type II neurones of Nambu &
      Llinas (1994, 1997) while the small diameter type B cells display morphological
      similarities with those described by Millhouse (1986). The rarely encountered
      type C cells may well be large cholinergic neurones. These findings provide a
      cellular basis for the study of intercellular communication and network
      interactions in the adult rat in vitro.

PMID- 10970428
TI  - Dendro-somatic distribution of calcium-mediated electrogenesis in purkinje cells
      from rat cerebellar slice cultures.
AB  - The role of Ca2+ entry in determining the electrical properties of cerebellar
      Purkinje cell (PC) dendrites and somata was investigated in cerebellar slice
      cultures. Immunohistofluorescence demonstrated the presence of at least three
      distinct types of Ca2+ channel proteins in PCs: the alpha1A subunit (P/Q type
      Ca2+ channel), the alpha1G subunit (T type) and the alpha1E subunit (R type). In
      PC dendrites, the response started in 66 % of cases with a slow depolarization
      (50 +/- 15 ms) triggering one or two fast (approximately 1 ms) action potentials
      (APs). The slow depolarization was identified as a low-threshold non-P/Q Ca2+ AP
      initiated, most probably, in the dendrites. In 16 % of cases, this response
      propagated to the soma to elicit an initial burst of fast APs. Somatic recordings
      revealed three modes of discharge. In mode 1, PCs display a single or a short
      burst of fast APs. In contrast, PCs fire repetitively in mode 2 and 3, with a
      sustained discharge of APs in mode 2, and bursts of APs in mode 3. Removal of
      external Ca2+ or bath applications of a membrane-permeable Ca2+ chelator
      abolished repetitive firing. Tetraethylammonium (TEA) prolonged dendritic and
      somatic fast APs by a depolarizing plateau sensitive to Cd2+ and to omega
      conotoxin MVII C or omega-agatoxin TK. Therefore, the role of Ca2+ channels in
      determining somatic PC firing has been investigated. Cd2+ or P/Q type Ca2+
      channel-specific toxins reduced the duration of the discharge and
      occasionallyinduced the appearance of oscillations in the membrane potential
      associated with bursts of APs. In summary, we demonstrate that Ca2+ entry through
      low-voltage gated Ca2+ channels, not yet identified, underlies a dendritic AP
      rarelyeliciting a somatic burst of APs whereas Ca2+ entry through P/Q type Ca2+
      channels allowed a repetitive firing mainly by inducing a Ca2+-dependent
      hyperpolarization.

PMID- 10970431
TI  - Responses of nerve fibres of the rat saphenous nerve neuroma to mechanical and
      chemical stimulation: an in vitro study.
AB  - The response of neuroma nerve endings to different stimuli was studied in a
      saphenous nerve neuroma preparation in vitro. Electrical activity was recorded
      from 141 single fibres dissected of saphenous nerve. One-third (27 %) displayed
      spontaneous activity. Based on their response to mechanical and chemical stimuli,
      neuroma nerve fibres were classified as mechanosensory fibres (47.5 %),
      mechanically insensitive chemosensory fibres (17.0 %), polymodal nociceptor
      fibres (28.4 %) and unresponsive fibres (7.1 %). Mechanosensory and polymodal
      neuroma endings responded to von Frey hair stimulation either with a few impulses
      (phasic units) or a sustained discharge (tonic units). Polymodal units were
      additionally activated by at least one of the following stimuli: acidic
      solutions; a combination of bradykinin, prostaglandin E2, serotonin, substance P
      and histamine (all at 1 microM) plus 7 mM KCl (inflammatory soup); 600 mM NaCl
      and capsaicin. Low pH solutions increased the firing discharge of polymodal
      endings proportionally to the proton concentration. The 'inflammatory soup'
      evoked a firing response characterized by the absence of tachyphylaxis, which
      appeared when its components were applied separately. Both stimuli sensitized
      polymodal fibres to mechanical stimulation. Hypertonic NaCl (600 mM) and
      capsaicin (3.3 mM) induced a prolonged discharge that outlasted the stimulus
      duration. Mechanically insensitive chemosensory neuroma fibres exhibited
      responses to chemical stimuli analogous to polymodal fibres. They became
      mechanically sensitive after chemical stimulation. These findings show that
      neuroma nerve endings in the rat saphenous nerve neuroma in vitro are
      functionally heterogeneous and exhibit properties reminiscent of those in intact
      mechanosensory, polymodal and 'silent' nociceptor sensory afferents, including
      their sensitization by algesic chemicals.

PMID- 10970432
TI  - P2 purinoceptor-mediated control of rat cerebral (pial) microvasculature;
      contribution of P2X and P2Y receptors.
AB  - Purine and pyrimidine nucleotides evoke changes in the vascular tone of medium to
      large cerebral vessels through the activation of P2 purinoceptors. We have
      applied P2 receptor drugs to rat pial arterioles and measured changes in
      arteriole diameter (o.d. 40-84 micrometer at rest), and recorded currents from
      arteriolar smooth muscle cells using patch-clamp techniques. Transient
      vasoconstrictions and rapidly inactivating currents were evoked by alpha,beta
      methylene ATP (0.1-30 micrometer) and were sensitive to the P2 receptor
      antagonists suramin and iso-PPADS. UTP and UDP (0.1-1000 micrometer) evoked
      sustained suramin-sensitive vasoconstrictions. ATP (0.1-1000 micrometer) and 2
      methylthioATP (2MeSATP, 300 micrometer) evoked transient vasoconstrictions
      followed by sustained vasodilatations. ADP application resulted in only
      vasodilatation (EC50 approximately 4 micrometer). Vasodilator responses to ATP,
      2MeSATP or ADP were unaffected by suramin (100 micrometer). RT-PCR analysis
      indicated that P2X1-7 and P2Y1,2,6 RNA can be amplified from the pial sheet. Our
      results provide direct evidence for the presence of functional P2X receptors with
      a phenotype resembling the P2X1 receptor subtype on cerebral resistance
      arterioles. The pharmacological properties of the pyrimidine-evoked responses
      suggest that a combination of P2Y2- and P2Y6-like receptors are responsible for
      the sustained vasoconstrictions. It is therefore likely that the nucleotides and
      their associated receptors are involved in a complicated regulatory system to
      control cerebral blood pressure.

PMID- 10970433
TI  - The role of K+ channels in the force recovery elicited by Na+-K+ pump stimulation
      in Ba2+-paralysed rat skeletal muscle.
AB  - The present experiments were performed to assess the role of K+ channels in
      hormonal stimulation of the Na+-K+ pump and to determine the contribution of Na+
      K+ pumps to the recovery of excitability and contractility in depolarized
      skeletal muscle. In soleus muscle, Ba2+ (0.02 and 1 mM) was found to inhibit 42K+
      efflux and 42K+ influx. Both in the absence and the presence of Ba2+ (1 mM),
      salbutamol and calcitonin gene-related peptide (CGRP) induced a marked decrease
      in intracellular Na+ and stimulation of 42K+ uptake. In soleus muscles Ba2+ (0.1
      and 1.0 mM) decreased twitch and tetanic force. Subsequent stimulation of the Na+
      K+ pumps by salbutamol, CGRP or repeated electrical stimulation produced a highly
      significant restoration of force development, which was suppressed by ouabain,
      but not by glibenclamide. Also, in extensor digitorum longus muscles Ba2+ (0.1
      mM) produced a considerable force decline, which was partly restored by
      salbutamol and CGRP. The area of compound action potentials (M-waves) elicited by
      indirect stimulation was decreased by Ba2+ (0.1 mM). This was associated with a
      concomitant decrease in tetanic force and depolarization. Salbutamol, CGRP or
      repeated electrical stimulation all elicited marked recovery of M-wave area,
      force and membrane potential. All recordings showed close correlations between
      these three parameters. The data add further support to the concept that due to
      its electrogenic nature and large transport capacity, the Na+-K+ pump is a rapid
      and efficient mechanism for the maintenance of excitability in skeletal muscle,
      acting independently of Ba2+- or ATP-sensitive K+ channel function.

PMID- 10970434
TI  - Glucocorticoids reduce interleukin-1 concentration and result in neuroprotective
      effects in rat heatstroke.
AB  - In urethane-anaesthetized rats, we assessed the protective effects of
      glucocorticoids against heatstroke-induced arterial hypotension and ischaemic
      neuronal damage. Heatstroke was induced by exposing the animals to an ambient
      temperature of 42 C. The time at which both the mean arterial pressure (MAP) and
      local cerebral blood flow (CBF) in the striatum decreased from their peak levels
      was taken as the onset of heatstroke. Control rats were exposed to a temperature
      of 24 C. The values of MAP and CBF after heatstroke onset were all significantly
      lower than those in control rats. However, the neuronal damage score in the
      striatum and serum levels of interleukin-1beta (IL-1beta) were greater. Systemic
      pretreatment or treatment with an exogenous glucocorticoid, dexamethasone (4 mg
      or 6 mg kg-1, i.v.), reduced the heatstroke-induced arterial hypotension, serum
      IL-1beta levels, cerebral ischaemia and neuronal damage, and resulted in
      prolongation of the time to death (TTD; the interval between the onset of heat
      stress and cardiac arrest). Following bilateral adrenalectomy, MAP, CBF and TTD
      values were found to be significantly lower in the adrenalectomized (ADX) rats
      than in the sham-ADX rats after heat exposure. These changes were attenuated by
      dexamethasone. The data support the argument that glucocorticoids reduce the
      plasma IL-1beta concentration and may provide the neuroprotective effects
      observed in rat heatstroke.

PMID- 10970435
TI  - Intrinsic properties of rat striatal output neurones and time-dependent
      facilitation of cortical inputs in vivo.

PMID- 10970436
TI  - Tetanus relaxation of fast skeletal muscles of the mouse made parvalbumin
      deficient by gene inactivation.
AB  - The effects of tetanus duration on the relaxation rate of extensor digitorum
      longus (EDL) and flexor digitorum brevis (FDB) muscles were studied in normal
      (wild-type, WT) and parvalbumin-deficient (PVKO) mice, at 20 C. In EDL of PVKO,
      the relaxation rate was low and unaffected by tetanus duration (< 3.2 s). In
      contrast, the relaxation rate of WT muscles decreased when tetanus duration
      increased from 0.2 to 3.2 s. In WT muscles, fast relaxation recovered as the rest
      interval increased. Specific effect of parvalbumin was asserted by calculating
      the difference in relaxation rate between WT and PVKO muscles. For EDL, the rate
      constant of relaxation slowing was 1.10 s-1 of tetanization; the rate constant of
      relaxation recovery was 0.05 s-1 of rest. In FDB, the effects of tetanus duration
      on WT and PVKO muscles were qualitatively similar to those observed in EDL.
      Relaxation slowing as tetanus duration increases, reflects the progressive
      saturation of parvalbumin by Ca2+, while recovery as rest interval increases
      reflects the return to Ca2+-free parvalbumin. At all tetanus durations,
      relaxation rate still remained slightly faster in WT muscles. This suggested that
      parvalbumin facilitates calcium traffic from myofibrils to the SR. No difference
      was found between WT and PVKO muscles for: (i) the expression of the fast
      isoforms of myosin heavy chains, (ii) the force-velocity relationship and maximal
      shortening velocity and (iii) the Ca2+-activated ATPase activity from isolated
      preparations of the sarcoplasmic reticulum (SR).

PMID- 10970437
TI  - Endogenous excitatory drive to the respiratory system in rapid eye movement sleep
      in cats.
AB  - A putative endogenous excitatory drive to the respiratory system in rapid eye
      movement (REM) sleep may explain many characteristics of breathing in that state,
      e.g. its irregularity and variable ventilatory responses to chemical stimuli.
      This drive is hypothetical, and determinations of its existence and character are
      complicated by control of the respiratory system by the oscillator and its
      feedback mechanisms. In the present study, endogenous drive was studied during
      apnoea caused by mechanical hyperventilation. We reasoned that if there was a REM
      dependent drive to the respiratory system, then respiratory activity should
      emerge out of the background apnoea as a manifestation of the drive.
      Diaphragmatic muscle or medullary respiratory neuronal activity was studied in
      five intact, unanaesthetized adult cats who were either mechanically
      hyperventilated or breathed spontaneously in more than 100 REM sleep periods.
      Diaphragmatic activity emerged out of a background apnoea caused by mechanical
      hyperventilation an average of 34 s after the onset of REM sleep. Emergent
      activity occurred in 60 % of 10 s epochs in REM sleep and the amount of activity
      per unit time averaged approximately 40 % of eupnoeic activity. The activity
      occurred in episodes and was poorly related to pontogeniculo-occipital waves. At
      low CO2 levels, this activity was non-rhythmic. At higher CO2 levels (less than
      0.5 % below eupnoeic end-tidal percentage CO2 levels in non-REM (NREM) sleep),
      activity became rhythmic. Medullary respiratory neurons were recorded in one of
      the five animals. Nineteen of twenty-seven medullary respiratory neurons were
      excited in REM sleep during apnoea. Excited neurons included inspiratory,
      expiratory and phase-spanning neurons. Excitation began about 43 s after the
      onset of REM sleep. Activity increased from an average of 6 impulses s-1 in NREM
      sleep to 15.5 impulses s-1 in REM sleep. Neuronal activity was non-rhythmic at
      low CO2 levels and became rhythmic when levels were less than 0.5 % below
      eupnoeic end-tidal levels in NREM sleep. The level of CO2 at which rhythmic
      neuronal activity developed corresponded to eupnoeic end-tidal CO2 levels in REM
      sleep. These results demonstrate an endogenous excitatory drive to the
      respiratory system in REM sleep and account for rapid and irregular breathing and
      the lower set-point to CO2 in that state.

PMID- 10970438
TI  - Influence of prenatal adrenaline infusion on arterial blood gases after caesarean
      delivery in the lamb.
AB  - The efficacy of pulmonary gas exchange immediately after delivery is inversely
      related to the volume of liquid in the lung at birth, but aspiration of as much
      liquid as possible from the lung before Caesarean delivery fails to improve
      postnatal oxygenation (Pa,O2) to the level achieved after spontaneous term
      delivery. We hypothesised that the differing respiratory benefit of aspiration
      and vaginal delivery results from the differing volume of lung liquid remaining
      after aspiration (17 ml (kg body weight)-1) and labour (7 ml kg-1). We addressed
      this hypothesis by reducing lung liquid volume to an estimated 7 ml kg-1 by
      infusing adrenaline to seven fetal lambs at 140 days gestation (term is 147 days)
      before performing Caesarean delivery and obtaining postnatal blood gases for
      comparison with samples from lambs delivered vaginally. Infusion of adrenaline to
      fetuses caused a progressive decline in arterial O2 saturation (Sa, O2), pH and
      base excess, but no change in arterial partial pressure of O2 (Pa,O2) or CO2
      (Pa,CO2). After birth, Pa,O2 rapidly rose to the same level in adrenaline-treated
      and vaginal-delivery groups. A severe acidosis occurred in the adrenaline-treated
      group and this appeared to be related to a higher Pa,CO2 and a transiently lower
      Sa, O2 in this group. We conclude that adrenaline infusion can enhance postnatal
      Pa,O2 levels in the newborn lamb, but this beneficial effect may be outweighed by
      the severe acidosis that develops after prolonged prenatal adrenaline treatment.

PMID- 10970440
TI  - Response of human muscle spindle afferents to sinusoidal stretching with a wide
      range of amplitudes.
AB  - Impulses of human single muscle spindle afferents were recorded from the m.
      extensor carpi radialis, while 1 Hz sinusoidal movements for a wide range of
      amplitudes (0.05-10 deg, half of the peak-to-peak amplitude) were imposed at the
      wrist joint. The response was considered as linear when the discharge was
      approximately sinusoidally modulated. The linearity was further checked by a
      linear increase in the response with the amplitude and a constancy of the phase
      and mean level. Fifteen of 25 primary afferents were active at rest with a mean
      rate of 10.6 impulses s-1 (median). The linear response to sinusoidal stretching
      was limited to amplitudes lower than about 1.0 deg. The sensitivity was 5.6
      impulses s-1 deg-1 (median) in the linear range and decreased at larger
      amplitudes. The other 10 primary afferents were silent at rest and lacked a
      linear response at low amplitudes. Nine secondary afferents were active at rest
      with a mean rate of 9.5 impulses s-1. The linear range extended up to about 4.0
      deg with a sensitivity of 1.4 impulses s-1 deg-1. In the linear range, the phase
      advance of the response to sinusoidal stretching was about 50 deg and was similar
      between the two types of spindle afferents. In primary afferents, the phase
      advance increased to nearly 90 deg outside the linear range. The findings suggest
      that high sensitivity to small stretches is important in determining primary
      afferent firing during natural movements in intact humans.

PMID- 10970439
TI  - Metabolic modulation of sympathetic vasoconstriction in human skeletal muscle:
      role of tissue hypoxia.
AB  - Sympathetically evoked vasoconstriction is modulated by skeletal muscle
      contraction, but the underlying events are incompletely understood. During
      contraction, intramuscular oxygenation decreases with increasing exercise
      intensity. We therefore hypothesized that tissue hypoxia plays a crucial role in
      the attenuation of sympathetic vasoconstriction in contracting skeletal muscle.
      In 19 subjects, near-infrared spectroscopy was used to measure decreases in
      muscle oxygenation (DeltatHbO2+MbO2) as an estimate of the vasoconstrictor
      response to reflex sympathetic activation with lower body negative pressure
      (LBNP) in the microcirculation of resting and contracting forearm muscles. Oxygen
      delivery to the muscles was reduced by decreasing (a) arterial O2 content by
      breathing 10 % O2, or (b) muscle perfusion by applying forearm positive pressure
      (FPP, +40 mmHg). In resting forearm, reflex sympathetic activation decreased
      muscle oxygenation by 11 +/- 1 %. Handgrip alone at 5 and 20 % of maximal
      voluntary contraction (MVC) decreased muscle oxygenation by 4 +/- 1 and 28 +/- 4
      %, respectively. When superimposed on handgrip, LBNP-induced decreases in muscle
      oxygenation were preserved during handgrip at 5 % MVC, but were abolished during
      handgrip at 20 % MVC. Oral administration of aspirin (1 g) did not restore the
      latter response. When the decrease in forearm muscle oxygenation elicited by
      handgrip at 20 % MVC was mimicked by either (a) systemic hypoxia plus 5 %
      handgrip (DeltatHbO2+MbO2, -32 +/- 3 %), or (b) hypoperfusion of resting muscle
      by FPP (DeltatHbO2+MbO2, -26 +/- 6 %), LBNP-induced decreases in muscle
      oxygenation were greatly attenuated. These data suggest that local tissue hypoxia
      is involved in the metabolic attenuation of sympathetic vasoconstriction in the
      microcirculation of exercising human skeletal muscle. The specific underlying
      mechanism remains to be determined, although products of the cyclo-oxygenase
      pathway do not appear to be involved.

PMID- 10970441
TI  - Induction of chromosomal aberrations by the rhodium(III) complex cis
      [Rh(biq)(2)Cl(2)]Cl in cultured human lymphocytes.
AB  - The genotoxicity of the rhodium(III) complex cis-[Rh(biq)(2)Cl(2)]Cl (complex R)
      in cultured human lymphocytes was studied using the chromosome aberrations (CAs)
      assay. Lymphocyte cultures were initiated from two adult healthy non-smoking male
      volunteers and were exposed to the complex for a duration of 3 or 20 h prior to
      cell collection. The reduction in mitotic indices (MI) and the induction of CAs
      represented the toxic and clastogenic effects of the different treatments,
      respectively. Complex R proved to be an intermediate toxic clastogen with a
      MI(50) of 1.0 microg/ml and a minimum positive dose (MPD) of 0.1 microg/ml. Like
      bleomycin, complex R exerted its clastogenic effects without the need for
      metabolic activation and induced CAs of all types in lymphocytes treated in the
      G(2) and late S phases and, therefore, can be considered a radiomimetic. In
      addition, it induced more total CAs of chromatid-type than of chromosome-type.
      The reduction in the frequencies of CAs following the 20 h treatment as compared
      with those induced following the 3 h treatments indicated that human lymphocytes
      in the presence of complex R can partially tolerate the lesions involved in CA
      production. Based on the biological effects of complex R and the similarities
      between its functional group and that of bleomycin, possible mechanisms for
      complex R genotoxicity are discussed.

PMID- 10970442
TI  - Mutation frequency in the lacI gene of liver DNA from lambda/lacI transgenic mice
      following the interaction of PCBs with iron causing hepatic cancer and porphyria.
AB  - The synergistic interaction of iron overload, AHR: genotype and exposure to a
      mixture of polychlorinated biphenyls (PCBs) (Aroclor 1254) in mice leads to
      hepatic porphyria, oxidative DNA damage and cancer. In humans, hepatocellular
      cancer is associated with iron overload and hepatic porphyria. Neither the
      mechanism of hepatic carcinogenesis induced by PCBs in rodents nor hepatocellular
      cancer induced by iron and porphyria in humans are understood. To test the
      hypothesis that chronic interaction of iron and PCBs may induce mutagenesis in
      liver DNA, lambda /lacI transgenic C57BL/6 mice were given iron dextran (600 mg
      iron/kg) and then administered Aroclor 1254 in the diet (0.01%) for 7 weeks.
      Hepatic iron, CYP1A activity and CYP1A1/1A2 protein were elevated >20-fold as a
      result of iron or Aroclor treatments, respectively, but porphyria with associated
      histological changes only developed in the combined iron/Aroclor treatment group.
      lambda/lacI shuttle vectors were isolated from liver genomic DNA and the
      mutational frequency (MF) in the lacI gene determined. Both iron and Aroclor
      treatments alone caused significant small increases in MF (1.5- and 1.4-fold,
      respectively), however, the MF following the combined iron and Aroclor treatment
      (1. 6-fold) was not greater than the additive effects. In contrast, the MF was
      significantly elevated (4.7-fold) in liver DNA of mice 2 weeks following five
      daily doses of N-nitrosodimethylamine (4 mg/kg). These studies demonstrate that
      neither PCBs nor iron overload caused marked point mutations even in a
      combination regime that leads to oxidative damage and cancer. There was also no
      strong evidence either that porphyrins or chronic CYP1A1 expression induced by
      the PCBs after this period caused marked point mutagens or simple deletions.
      Hence, to understand the PCBs-iron synergism more complex scenarios than point
      mutations or simple deletions must be invoked.

PMID- 10970443
TI  - Maleic hydrazide induces genotoxic effects but no DNA damage detectable by the
      comet assay in tobacco and field beans.
AB  - The plant growth regulator and herbicide maleic hydrazide (MH) induced a high
      frequency of somatic mutations in leaves of tobacco (Nicotiana tabacum var.
      xanthi) and a high yield of chromosome aberrations in roots of field beans (Vicia
      faba, karyotype ACB). In contrast, no significant increase in MH-induced DNA
      damage, as measured by the Comet assay, could be demonstrated in either plant
      species. The absence of DNA migration induced by MH was not effected in tobacco
      by either pH of the MH solution, the sampling time after MH treatment or
      continuous MH treatment for 14 days. To our knowledge, MH represents the first
      agent which has proved to be highly mutagenic and clastogenic but does not cause
      DNA damage as measured by the Comet assay in the same experimental system.

PMID- 10970444
TI  - Mutagenicity of diesel exhaust particles from two fossil and two plant oil fuels.
AB  - Particulate matter of diesel engine exhaust from four different fuels was studied
      for content of polynuclear aromatic compounds and mutagenic effects. Two so
      called biodiesel fuels, rapeseed oil methylesters (RME) and soybean oil
      methylesters (SME), were compared directly with two fossil diesel fuels with the
      normal (DF) and a low sulfur content (LS-DF). Diesel exhaust particles were
      sampled on filters from the diluted and cooled exhaust of a test engine at five
      different speeds and loads. Filters were weighed for total particulate matter,
      Soxhlet extracted with dichloromethane and the content of insoluble material
      determined. The soluble organic fraction was analysed for polynuclear aromatic
      compounds. Mutagenicity was determined using the Salmonella typhimurium/mammalian
      microsome assay with strains TA98 and TA100. Compared with DF, the exhaust
      particles of LS-DF, RME and SME contained less insoluble material, which
      consisted mainly of the carbon cores of diesel exhaust particles. The
      concentrations of individual polynuclear aromatic compounds varied widely among
      the different exhaust extracts, but total concentrations of the compounds were
      approximately double for DF and SME compared with LS-DF and RME. In TA98
      significant increases in mutation rates were obtained for the soluble organic
      fractions of all fuels for engines running at full speed (load modes A and D),
      but for DF revertants were 2- to 10-fold more frequent as compared with LS-DF,
      RME and SME. Revertant frequencies for DF and partly for LS-DF were also elevated
      in TA100, while RME and SME gave no significant increase in mutations. The
      results indicate that diesel exhaust particles from RME, SME and LS-DF contain
      less black carbon and total polynuclear aromatic compounds and are significantly
      less mutagenic in comparison with DF. A high sulfur content of the fuel and high
      engine speeds (rated power) and loads are associated with an increase in
      mutagenicity of diesel exhaust particles.

PMID- 10970445
TI  - Glutathione S-transferase mu1 (GSTM1) status and bladder cancer risk: a meta
      analysis.
AB  - Inter-individual differences in bladder cancer susceptibility may be mediated in
      part through polymorphic variability in the bioactivation and detoxification of
      procarcinogens. Glutathione S-transferase mu1 (GSTM1) status has been extensively
      studied as a risk factor in this context. To clarify the impact of GSTM1
      deficiency on bladder cancer risk a meta-analysis of 15 case-control studies from
      the literature has been carried out using a random effects model. The principal
      outcome measure was the odds ratio for the risk of bladder cancer. Pooling the
      studies the odds ratio of bladder cancer risk associated with GSTM1 deficiency
      was 1.53 (95% confidence limits 1.28-1.84). The relationship between GSTM1 status
      and bladder cancer risk was not confined to a specific population. This meta
      analysis supports the hypothesis that GSTM1 deficiency is a determinant of
      bladder cancer susceptibility. A review of studies does, however, indicate that
      greater attention should therefore be paid to the design of future studies. The
      interaction between GSTM1 and other polymorphisms on the risk of bladder cancer
      and their interaction with environmental risk factors will only be addressed by
      well-designed studies based on sample sizes commensurate with the detection of
      small genotypic risks.

PMID- 10970446
TI  - Mutagenicity and loss of heterozygosity at the APRT locus in human lymphoblastoid
      cells exposed to 3'-azido-3'-deoxythymidine.
AB  - Previous experiments in our research group showed that 3'-azido-3'-deoxythymidine
      (AZT) caused increased mutant frequencies (Mfs) at the X-linked hypoxanthine
      guanine phosphoribosyltransferase (HPRT) and the autosomal thymidine kinase (TK)
      genes in human lymphoblastoid cells and that there was a significant positive
      correlation between AZT incorporation into cellular DNA and AZT-induced TK Mfs.
      In the current study, the mutagenicity of AZT was further evaluated at the
      autosomal adenine phosphoribosyltransferase (APRT) gene. AZH1 cells, a human
      lymphoblastoid cell line heterozygous at the APRT locus, were exposed to 300
      microM AZT for 0, 1, 3 or 6 days or to 0, 33, 100, 300 or 900 microM AZT for 3
      days (n = 5 flasks/group). A cell cloning assay was used to quantitate APRT Mfs.
      AZT-induced APRT Mf increased with extended duration and with incremental
      concentrations of AZT exposure. There was a positive correlation (P = 0.022,
      coefficient = 0.93) between AZT incorporation into DNA and AZT-induced APRT Mfs.
      RFLP analyses indicated that AZT exclusively induced loss of heterozygosity in
      APRT mutants. These results, which are consistent with findings on the
      mutagenicity of AZT at the HPRT and TK genes, indicate the need for further
      investigations on the potential long-term side effects of AZT on humans,
      especially those who receive AZT for a prophylactic reason.

PMID- 10970447
TI  - The mammalian gene mutation database.
AB  - The Mammalian Gene Mutation Database (MGMD) is a comprehensive collection of
      published mutation data from the open literature on mammalian cell-based gene
      model mutation detection systems. The database currently contains approximately
      30000 comprehensively described mutant spectra records and it is maintained and
      up- dated on a daily basis. The major objectives of the MGMD were (i) to provide
      an Internet-accessible database (http://lisntweb.swan.ac. uk/cmgt/index.htm) for
      chemically induced and spontaneous mutation types and spectra in selected genes;
      (ii) to standardize the reporting of mutations within different genes where
      ambiguity exists in the literature; and (iii) to provide interactive and user
      friendly access to the information. A multi-option search facility has been
      included that allows the user to search the database for parameters such as
      mutagen, gene or cell type of interest. The structure of the database permits
      easy retrieval of specific mutation data for further analysis. Thus, the MGMD
      should become a useful and necessary reference source and provides an analysis
      tool for genetic toxicologists.

PMID- 10970448
TI  - Biological mass spectrometry: a primer.
AB  - Biological polymers undergo numerous significant and fascinating interactions,
      such as post-translational modifications, non-covalent associations and
      conformational changes. A valuable parameter for the characterization of a
      biopolymer is molecular weight. Modern methods of mass spectrometry, including
      electrospray ionization and matrix-assisted laser desorption ionization mass
      spectrometry, are ideally suited for the accurate determination of the molecular
      weight of a biopolymer of interest. Molecular weight measurements are now
      routinely utilized in the qualitative and quantitative analysis of
      macromolecules. In many cases small sample quantities (i.e. a few micrograms)
      limit the utility of nuclear magnetic resonance spectroscopy and X-ray
      crystallography in obtaining structural information. Thus, mass spectrometry
      offers an attractive alternative to the more traditional bioanalytical methods
      for rapid and sensitive measurements. The ultimate goal of these experiments is
      to obtain sufficient information in order to map the complex molecular circuitry
      which operates within the cell. In the analysis of complex mixtures mass
      spectrometry is even more powerful when utilized in conjunction with separation
      methods. Herein we present some of the aspects of modern biological mass
      spectrometry for the investigation of large molecules. For more advanced or
      detailed technical descriptions we refer the reader to a number of recently
      published reports.

PMID- 10970449
TI  - Abstracts of the united kingdom environmental mutagen society 24(th)Annual
      general meeting, july 2-5, university of wales swansea, swansea, UK

PMID- 10970450
TI  - Inflammatory bowel disease.

PMID- 10970451
TI  - The many faces of vitamin D deficiency rickets.

PMID- 10970453
TI  - Scrotal swelling in children.

PMID- 10970452
TI  - Hepatomegaly in neonates and children.

PMID- 10970454
TI  - Index of suspicion.

PMID- 10970455
TI  - Earning CME credit-completing the PIR quiz

PMID- 10970456
TI  - A febrile infant who has hand edema and erythema.

PMID- 10970457
TI  - Proposal for the measurement of bell-type correlations from continuous variables
AB  - We show theoretically that Bell-type correlations can be observed between
      continuous variable measurements performed on a parametric source. An auxiliary
      measurement, performed on the detection environment, negates the possibility of
      constructing a local realistic description of these correlations.

PMID- 10970458
TI  - Imaging the phase of an evolving bose-einstein condensate wave function
AB  - We demonstrate a spatially resolved autocorrelation measurement with a Bose
      Einstein condensate and measure the evolution of the spatial profile of its
      quantum mechanical phase. Upon release of the condensate from the magnetic trap,
      its phase develops a form that we measure to be quadratic in the spatial
      coordinate. Our experiments also reveal the effects of the repulsive interaction
      between two overlapping condensate wave packets and we measure the small momentum
      they impart to each other.

PMID- 10970459
TI  - Gravitational waves from mesoscopic dynamics of the extra dimensions
AB  - Recent models which describe our world as a brane embedded in a higher
      dimensional space introduce new geometrical degrees of freedom, associated with
      spatial variations in the position of the brane and the size of the extra
      dimensions, that can be coherently excited by symmetry breaking in the early
      universe even on "mesoscopic" scales as large as 1 mm. The characteristic
      frequency and intensity of resulting gravitational radiation backgrounds are
      estimated. Extra dimensions with scale between 10(-14) and 1 mm can produce
      detectable backgrounds at frequencies f approximately 10(3) to 10(-4) Hz.

PMID- 10970460
TI  - Prospects of detecting baryon and quark superfluidity from cooling neutron stars
AB  - Baryon and quark superfluidity in the cooling of neutron stars are investigated.
      Future observations will allow us to constrain combinations of the neutron or
      Lambda-hyperon pairing gaps and the star's mass. However, in a hybrid star with a
      mixed phase of hadrons and quarks, quark gaps larger than a few tenths of an MeV
      render quark matter virtually invisible for cooling. If the quark gap is smaller,
      quark superfluidity could be important, but its effects will be nearly impossible
      to distinguish from those of other baryonic constituents.

PMID- 10970461
TI  - Complementarity of the maldacena and randall-sundrum pictures
AB  - We revive an old result, that one-loop corrections to the graviton propagator
      induce 1/r(3) corrections to the Newtonian gravitational potential, and compute
      the coefficient due to closed loops of the U(N) N = 4 super-Yang-Mills theory
      that arises in Maldacena's anti-de Sitter conformal field theory correspondence.
      We find exact agreement with the coefficient appearing in the Randall-Sundrum
      brane-world proposal. This provides more evidence for the complementarity of the
      two pictures.

PMID- 10970462
TI  - Search for second and third generation leptoquarks including production via
      technicolor interactions in p&pmacr; collisions at radicals = 1.8 TeV
AB  - We report the results of a search for second and third generation leptoquarks
      using 88 pb(-1) of data recorded by the Collider Detector at Fermilab. Color
      triplet technipions, which play the role of scalar leptoquarks, are investigated
      due to their potential production in decays of strongly coupled color octet
      technirhos. Events with a signature of two heavy flavor jets and missing energy
      may indicate the decay of a second (third) generation leptoquark to a charm
      (bottom) quark and a neutrino. As the data are found to be consistent with
      standard model expectations, mass limits are determined.

PMID- 10970463
TI  - Search for new particles decaying to t&tmacr; in p&pmacr; collisions at radicals
      = 1.8 TeV
AB  - We use 106 pb (-1) of data collected with the Collider Detector at Fermilab to
      search for narrow-width, vector particles decaying to a top and an antitop quark.
      Model independent upper limits on the cross section for narrow, vector resonances
      decaying to t&tmacr; are presented. At the 95% confidence level, we exclude the
      existence of a leptophobic Z' boson in a model of top-color-assisted technicolor
      with mass M(Z')<480 GeV/c(2) for natural width gamma = 0.012M(Z'), and M(Z')<780
      GeV/c(2) for gamma = 0.04M(Z').

PMID- 10970464
TI  - Fermions obstruct dimensional reduction in hot QCD
AB  - We have studied, for the first time, screening masses obtained from glueball-like
      correlators in quantum chromodynamics with four light dynamical flavors of quarks
      in the temperature range 1. 5T(c)</=T</=3T(c), where T(c) is the temperature at
      which the chiral transition occurs. We have also studied pionlike and sigmalike
      screening masses and found that they are degenerate in the entire range of T.
      These obstruct perturbative dimensional reduction since the lowest glueball
      screening mass is heavier than them. Extrapolation of our results suggests that
      this obstruction may affect the entire range of temperature expected to be
      reached even at the Large Hadron Collider.

PMID- 10970465
TI  - Fluctuation probes of quark deconfinement
AB  - The size of the average fluctuations of net baryon number and electric charge in
      a finite volume of hadronic matter differs widely between the confined and
      deconfined phases. These differences may be exploited as indicators of the
      formation of a quark-gluon plasma in relativistic heavy-ion collisions, because
      fluctuations created in the initial state survive until freeze-out due to the
      rapid expansion of the hot fireball.

PMID- 10970466
TI  - Charged particle ratio fluctuation as a signal for quark-gluon plasma
AB  - In this Letter we argue that the event-by-event fluctuations of the ratio of the
      positively charged and the negatively charged pions provide a signal for a quark
      gluon plasma. The fact that quarks carry fractional charges is ultimately
      responsible for this distinct signal.

PMID- 10970467
TI  - Nonsaturation of the J/psi suppression at large transverse energy in the comovers
      approach
AB  - We show that, contrary to recent claims, the J/psi suppression resulting from its
      interaction with comovers does not saturate at large transverse energy E(T). On
      the contrary, it shows a characteristic structure-a change of curvature near the
      knee of the E(T) distribution-which is due to the E(T) (or multiplicity)
      fluctuation. This change of curvature is also present in recent experimental
      results, although the experimetal effect is larger than in our calculation.

PMID- 10970468
TI  - Are crossings of energy levels and charge exchange really quantum phenomena?
AB  - Electron terms in the field of two stationary Coulomb centers (TCC) of charges Z
      and Z' can have crossings and quasicrossings. A quasicrossing, by enhancing
      charge exchange, can result in a dip in the spectral line profile emitted by a Z
      ion from a plasma consisting of both Z and Z' ions. The paradigm is that all of
      the above are inherently quantum phenomena. Here we disprove this paradigm. Based
      on first principles without model assumptions, we present a purely classical
      description of both the level crossings in the TCC problem and the dips in the
      spectral line profiles.

PMID- 10970469
TI  - Nonlinear magneto-optical rotation via alignment-to-orientation conversion
AB  - Nonlinear magneto-optical rotation is investigated at high light powers where the
      rotation is significantly modified by ac Stark shifts. These shifts are shown to
      change the overall sign of rotation for closed F-->F+1 transitions compared to
      the low light power limit. The effect is demonstrated by measurements in rubidium
      and density matrix calculations. The results are important for applications of
      nonlinear optical rotation such as sensitive magnetometry.

PMID- 10970470
TI  - Stable, strongly attractive, two-state mixture of lithium fermions in an optical
      trap
AB  - We use an all-optical trap to confine a strongly attractive two-state mixture of
      lithium fermions. By measuring the rate of evaporation from the trap, we
      determine the effective elastic scattering cross section 4pia(2) to show that the
      magnitude of the scattering length |a| is very large, in agreement with
      predictions. We show that the mixture is stable against inelastic decay provided
      that a small bias magnetic field is applied. For this system, the s-wave
      interaction is widely tunable at low magnetic field, and can be turned on and off
      rapidly via a Raman pi pulse. Hence, this mixture is well suited for fundamental
      studies of an interacting Fermi gas.

PMID- 10970471
TI  - Direct observation of a breit-wigner phase of a wave function
AB  - The Breit-Wigner phase of a wave function was obtained by measuring the
      interference between two independent ionization paths of a molecule. The state of
      interest was present in only one of the paths, thereby producing a phase shift in
      the observed signal. An analytical theory was used to determine the phase of the
      wave function from the observable.

PMID- 10970472
TI  - Fluctuations and the energy-optimal control of chaos
AB  - The energy-optimal entraining of the dynamics of a periodically driven
      oscillator, moving it from a chaotic attractor to a coexisting stable limit
      cycle, is investigated via analysis of fluctuational transitions between the two
      states. The deterministic optimal control function is identified with the
      corresponding optimal fluctuational force, which is found by numerical and analog
      simulations.

PMID- 10970473
TI  - Creation of localized optical waves that Do not obey the radiation condition at
      infinity
AB  - We show that the diffraction of a shocking optical pulse formed in a nonlinear
      transparent dielectric creates an optical missile, or localized radiation field
      whose amplitude and energy decays are slower than 1/R and 1/R(2), respectively,
      far from the aperture. Dispersion does not eliminate, but limits missile behavior
      to a finite range. Experimental techniques for optical missile generation are
      suggested.

PMID- 10970474
TI  - Three-dimensional nonlinear dynamics of thin liquid films
AB  - Three-dimensional dynamics of thin Newtonian liquid films subjected to long-range
      van der Waals forces on a horizontal coated solid surface is numerically studied
      in the framework of the long-wave theory. The dynamics of nonvolatile films
      results in the emergence of an isolated steady drop standing on a practically
      flat film, while volatile films uniformly disappear on the macroscale. In both
      cases the evolution of the initial small-amplitude noise spans over the stages of
      self-organization, fast thinning of the depressions, formation and expansion of
      the "holes," emergence of the polygonal network of liquid ridges, and its
      breakup, as seen in the experiments.

PMID- 10970475
TI  - Stability considerations associated with the meniscoid particle band at advancing
      interfaces in hele-shaw suspension flows
AB  - In the free surface flow of dense suspensions in confined domains, spontaneous
      particle enrichment occurs in the region adjacent to the free surface with an
      attendant increase in the effective viscosity. We present experimental evidence
      that this particle accretion introduces stability considerations that would
      otherwise not exist if the suspension remained uniform. For conditions favoring
      global stability, a local fingering instability can occur in the accretion band.
      For conditions favoring global instability, accretion can suppress the global
      growth of viscous fingers at the interface.

PMID- 10970476
TI  - Surface spiral waves in a filamentary vortex
AB  - Spiral surface waves emitted from a vertical vortex are studied experimentally.
      It is found that, similar to what occurs in the scattered wave of electrons for
      the Aharonov-Bohm effect, the number of arms of these waves is linked to
      circulation flux and therefore to the number of dislocations in the wave front.

PMID- 10970477
TI  - Control of density fluctuations and electron transport in the reversed-field
      pinch
AB  - A recent study conducted on the Madison Symmetric Torus reversed-field pinch has
      shown that control of density fluctuations can be achieved through modification
      of the current density profile. Most of the power in the density fluctuations is
      directly associated with core-resonant resistive tearing modes. We report that,
      during auxiliary current drive experiments, these density fluctuations are
      reduced about an order of magnitude over the entire plasma cross section and the
      resulting electron confinement is increased eightfold.

PMID- 10970478
TI  - Mutual attraction of laser beams in plasmas: braided light
AB  - Using a variational method, we show that an effective attractive force exists
      between two Gaussian laser beams in a plasma because of a mutual coupling from
      relativistic mass corrections. The effective force can be generalized to other
      nonlinearities. This force can cause two laser beams to spiral around each other
      with a rotation period that is proportional to the Rayleigh length. These orbits
      are stable if the ratio of the orbit diameter to the laser spot size
      d(0)/W(0)</=sqrt[2]. Three-dimensional particle-in-cell simulations are presented
      which confirm the mutual attraction.

PMID- 10970479
TI  - Collective stopping and ion heating in relativistic-electron-beam transport for
      fast ignition
AB  - Filamented transport of laser-generated relativistic electron beams in a plasma
      is studied with reference to fast ignition of fusion targets. The study is based
      on transverse two-dimensional particle-in-cell simulation. Coalescence of current
      filaments and related ion dynamics are found to determine beam stopping and ion
      heating.

PMID- 10970480
TI  - Chemical shift resolved photoionization cross sections of amorphous carbon
      nitride
AB  - The various components in the N 1s photoemission spectra of amorphous carbon
      nitride are identified by measuring their photon energy dependence and comparing
      the experimental results with ab initio multiple scattering calculations. The
      intensity modulations with photon energy are due to the extended x-ray absorption
      fine structure effects.

PMID- 10970481
TI  - Nature of the short wavelength excitations in vitreous silica: An X-Ray brillouin
      scattering study
AB  - The dynamical structure factor [ S(Q,E)] of vitreous silica has been measured by
      inelastic x-ray scattering varying the exchanged wave vector ( Q) at fixed
      exchanged energy ( E)-an experimental procedure that, contrary to the usual one
      at constant Q, provides spectra with much better identified inelastic features.
      This allows us to obtain the first direct evidence of Brillouin peaks in the
      S(Q,E) of SiO2 at energies above the boson peak (BP) energy, a finding that
      excludes the possibility that the BP marks the transition from propagating to
      localized dynamics in glasses.

PMID- 10970482
TI  - Temperature and pressure scaling of the alpha relaxation process in fragile glass
      formers: A dynamic light scattering study
AB  - The dynamics of two fragile glass forming liquids was studied as a function of
      temperature and pressure using dynamic light scattering. On the basis of measured
      data we evaluated the pressure and temperature scaling of the alpha relaxation.
      All the isotherms can be superimposed and form a master curve when the reduced
      relaxation times are plotted versus reduced pressure. The Kohlrausch-Williams
      Watts stretching parameter beta(KWW) is increasing with increasing temperature
      and decreasing pressure and plotted versus log<tau(KWW)> follows a master curve
      at all temperatures and pressures studied.

PMID- 10970483
TI  - Direct absorption of gas-phase atomic hydrogen by si(100): A narrow temperature
      window
AB  - Absorption of thermal-energy gaseous hydrogen atoms by Si(100), exceeding by far
      the dopant and other impurity concentrations, occurs within a narrow substrate
      temperature (T(s)) window centered at approximately 460 K. The absorbed hydrogen
      persists in the crystalline bulk as highly mobile species before migrating out
      and desorbing as molecular hydrogen at T(s) as high as 900 K, well above the
      recombinative desorption temperatures of surface-adsorbed H. Developing and
      sustaining atomic-scale surface roughness, by H-induced silicon etching, is a
      prerequisite for H absorption and determines the T(s) window.

PMID- 10970484
TI  - Observation of a superfluid He-3 A- B phase transition in silica aerogel
AB  - New NMR studies of 3He in high-porosity aerogel reveal a phase transition from an
      A-like to a B-like phase on cooling. The evidence includes frequency shift and
      magnetic susceptibility data, and similar behavior is found in two quite
      different aerogel samples. The A-like phase is stable only very near to T(c) but
      can be supercooled to below 0.8T(c). This behavior has been seen clearly at 32-
      and 24-bar pressures, and the presence of negative frequency shifts suggests that
      an A-like phase exists near T(c) at pressures as low as 12 bars in a magnetic
      field of 28.4 mT.

PMID- 10970485
TI  - Thermal roughening of a thin film: A new type of roughening transition
AB  - The equilibrium thermal roughening of thin Ge layers (one and two monolayers)
      deposited on Si(001) has been investigated with low-energy electron microscopy. A
      Ge-coverage-dependent roughening is observed. For two monolayers, the temperature
      at which imaging contrast is lost due to surface roughness is 900+/-25 degrees C,
      between the roughening temperatures of Ge(001) and Si(001). Lower Ge coverages
      move this temperature closer to that of Si(001). The roughening is confined to
      the Ge overlayers. It is believed that this phenomenon represents a new type of
      surface roughening transition that should be generally applicable for
      heteroepitaxial films.

PMID- 10970486
TI  - Quenching of giant hysteresis effects in La(1-z)Y(z)Hx switchable mirrors
AB  - The giant intrinsic hysteresis as a function of hydrogen concentration x in the
      optical and electrical properties of the archetypal switchable mirror YHx is
      eliminated by alloying Y with the chemically similar La. The La(1-z)Y(z)Hx films
      with z</=0.67 are essentially hysteresis-free. The origin of the large hysteresis
      of alloys with z>/=0.86 is the large uniaxial lattice expansion that accompanies
      their fcc to hexagonal phase transition in combination with lateral clamping.

PMID- 10970487
TI  - Quantum theory of the smectic metal state in stripe phases
AB  - We present a theory of the electron smectic fixed point of the stripe phases of
      doped layered Mott insulators. We show that in the presence of a spin gap three
      phases generally arise: (a) a smectic superconductor, (b) an insulating stripe
      crystal, and (c) a smectic metal. The latter phase is a stable two-dimensional
      anisotropic non-Fermi liquid. In the absence of a spin gap there is also a more
      conventional Fermi-liquid-like phase. The smectic superconductor and smectic
      metal phases (or glassy versions thereof) may have already been seen in Nd-doped
      La2-xSrxCuO4.

PMID- 10970488
TI  - Small-angle shubnikov-de haas measurements in a 2D electron system: the effect of
      a strong In-plane magnetic field
AB  - Measurements in magnetic fields applied at small angles relative to the electron
      plane in silicon MOSFETs indicate a factor of 2 increase of the frequency of
      Shubnikov-de Haas oscillations at H>H(sat). This signals the onset of full spin
      polarization above H(sat), the parallel field above which the resistivity
      saturates to a constant value. For H<H(sat), the phase of the second harmonic of
      the oscillations relative to the first is consistent with scattering events that
      depend on the overlap instead of the sum of the spin-up and spin-down densities
      of states. This unusual behavior may reflect the importance of many-body
      interactions.

PMID- 10970489
TI  - Excitonic effects in core-excitation spectra of semiconductors
AB  - Core-electron excitation spectra are used widely for structural and chemical
      analysis of materials, but interpretation of the near-edge structure remains
      unsettled, especially for semiconductors. For the important Si L(2,3) edge, there
      are two mutually inconsistent interpretations, in terms of effective-mass
      excitons and in terms of Bloch conduction-band final states. We report ab initio
      calculations and show that neither interpretation is valid and that the near-edge
      structure is in fact dominated by short-range electron-hole interactions even
      though the only bound excitons are effective-mass-like.

PMID- 10970490
TI  - Quasiparticle bound states around impurities in d(x(2)-y(2))-wave superconductors
AB  - Zn and Ni impurities in the hole-doped high-temperature superconductors are known
      to have strong effects on thermodynamic and transport properties. A recent
      scanning tunneling microscope study of Zn-doped Bi2212 [S. H. Pan et al., Nature
      (London) 403, 746 (2000)] has provided high-resolution images of the local
      density of states around nonmagnetic impurities in d(x(2)-y(2))-wave
      superconductors. These pictures contain detailed information about the spinor
      wave functions u(r) and v(r) of bound states with energy E0 approximately
      Delta/30, centered at the Zn sites. We show that this type of wave function
      follows from the solutions of the Bogoliubov-de Gennes equations for d(x(2)-y(2))
      wave superconductors.

PMID- 10970491
TI  - Thermodynamic fingerprints of disorder in flux line lattices and other glassy
      mesoscopic systems
AB  - We examine probability distributions for thermodynamic quantities in finite-sized
      random systems close to criticality. Guided by available exact results, a general
      ansatz is proposed for replicated free energies, which leads to scaling forms for
      cumulants of various macroscopic observables. For the specific example of a
      planar flux line lattice in a two-dimensional superconducting film near H(c1), we
      provide detailed scaling results for the statistics of the magnetic flux density,
      susceptibility, heat capacity, and their cross correlations, which can be tested
      in a recently used experimental setup [Bolle et al., Nature (London) 399, 43
      (1999)].

PMID- 10970492
TI  - Pressure dependence of T(c) in Y-Ba-Cu-O superconductors
AB  - By considering the recent widely accepted dispersion of electronic structure in
      cuprates, we analyze the pressure effect on the superconducting transition
      temperature T(c) in Y-Ba-Cu-O systems. Two intrinsic variables, i.e., the
      effective attractive interaction V(eff) and the hole concentration n(H) in the
      CuO2 plane, are proposed to be responsible for the pressure effect on T(c).
      Theoretical calculations agree well with experiments. Our results also suggested
      that the in-plane lattice parameter dependence of effective attraction V(eff)
      obeys dlnV(eff)/dlna = -4 approximately -2 for Y-Ba-Cu-O systems.

PMID- 10970493
TI  - Ultrashort microwave pulses generated due to three magnon interactions
AB  - Extremely narrow 2 ns wide microwave pulses are generated from nonlinear
      magnetostatic surface waves in yttrium iron garnet films. The shortest output
      pulse with the highest amplitude is achieved for input power levels of about 300
      mW and a carrier frequency below 3.3 GHz. The results are explained within the
      model based on dipole exchange spin wave modes involved in three magnon
      processes. The characteristic time for these processes to develop, as estimated
      from the smallest fall time of output pulse, is 1 ns. The relevant modes are
      verified by Brillouin light scattering.

PMID- 10970494
TI  - Magnetic-octupole order in neptunium dioxide?
AB  - The phase transition occurring at 25 K in NpO2, discovered almost 50 years ago,
      is the most long-lasting mystery in the physics of actinide compounds. Theories
      based on magnetic or electric-quadrupole order lead inevitably to fundamental,
      qualitative inconsistencies with observations. We show that the phenomenology of
      NpO2 can be understood if the order parameter is assumed to be a magnetic
      octupole of gamma(2) ( xyz) symmetry. NpO2 is the first compound for which
      indications of an octupolar phase transition have been found.

PMID- 10970495
TI  - Phenomenological model of dynamic nonlinear response of relaxor ferroelectrics
AB  - A phenomenological model was proposed which describes frequency dispersion of
      nonlinear dielectric response of relaxor ferroelectrics (relaxors) as a result of
      dispersion of their linear dielectric permittivity. The model was applied to
      Pb(Mg(1/3)Nb(2/3))O3 (PMN) relaxor. It provided a good qualitative description of
      temperature and frequency dependence of the third harmonics of PMN. Analysis
      within the model yielded a frequency independent nonlinear coefficient
      corresponding to static nonlinear dielectric susceptibility. The model explained
      the recently reported for PMN data on the Vogel-Fulcher law for frequency
      dependence of the temperature at which the third harmonics passes a maximum.

PMID- 10970496
TI  - Ultrafast spectroscopy of even-parity states in pi-conjugated polymers
AB  - Relaxation dynamics of even parity ( A(g)) states in poly( p-phenylene vinylene)
      derivatives are studied using a novel fsec transient spectroscopy, in which two
      different excitation pulses successively generate odd parity ( 1 (1)B(u))
      excitons at 2.2 eV and then reexcite them to higher A(g) states. For reexcitation
      energies Planck's over 2piomega<1.1 eV ultrafast internal conversion back to 1
      (1)B(u) takes place in accordance with Vavilov-Kasha's rule. However, for
      Planck's over 2piomega>1.1 eV the decay occurs in a nonemissive state identified
      as a polaron pair, showing that the A(g) states above 3.3 eV mediate charge
      transfer.

PMID- 10970497
TI  - Size-dependent electron-electron interactions in metal nanoparticles
AB  - The internal thermalization dynamics of the conduction electrons is investigated
      in silver nanoparticles with radius ranging from 13 to 1.6 nm using a femtosecond
      IR pump-UV probe absorption saturation technique. A sharp increase of the
      electron energy exchange rate is demonstrated for nanoparticles smaller than 5
      nm. The results are consistent with electron-electron scattering acceleration due
      to surface induced reduction of the Coulomb interaction screening by the
      conduction and core electrons.

PMID- 10970498
TI  - Ultrafast optical nonlinearity in the quasi-one-dimensional mott insulator
      Sr2CuO3
AB  - We report strong instantaneous photoinduced absorption in the quasi-one
      dimensional Mott insulator Sr2CuO3 in the IR spectral region. The observed
      photoinduced absorption is to an even-parity two-photon state that occurs
      immediately above the absorption edge. Theoretical calculation based on a two
      band extended Hubbard model explains the experimental features and indicates that
      the strong two-photon absorption is due to a very large dipole coupling between
      nearly degenerate one- and two-photon states. Room temperature picosecond
      recovery of the optical transparency suggests the strong potential of Sr2CuO3 for
      all-optical switching.

PMID- 10970499
TI  - Fast quantum gates for neutral atoms
AB  - We propose several schemes for implementing a fast two-qubit quantum gate for
      neutral atoms with the gate operation time much faster than the time scales
      associated with the external motion of the atoms in the trapping potential. In
      our example, the large interaction energy required to perform fast gate
      operations is provided by the dipole-dipole interaction of atoms excited to low
      lying Rydberg states in constant electric fields. A detailed analysis of
      imperfections of the gate operation is given.

PMID- 10970500
TI  - Spontaneous symmetry breaking turing-type pattern formation in a confined
      Dictyostelium cell mass.
AB  - We have discovered a new type of patterning which occurs in a two-dimensionally
      confined cell mass of the cellular slime mold Dictyostelium discoideum. Besides
      the longitudinal structure reported earlier, we observed a spontaneous symmetry
      breaking spot pattern whose wavelength shows similar strain dependency to that of
      the longitudinal pattern. We propose that these structures are due to a reaction
      diffusion Turing instability similar to the one which has been exemplified by
      CIMA (chlorite-iodide-malonic acid) reaction. The present finding may exhibit the
      first biochemical Turing structure in a developmental system with a controllable
      boundary condition.

PMID- 10970502
TI  - Violation of Bell's inequality by a generalized einstein-podolsky-rosen state
      using homodyne detection
AB  - Using homodyning with weak coherent fields and photon counting, we have observed
      violations of Bell-type inequalities by the generalized Einstein-Podolsky-Rosen
      state produced in a pulsed nondegenerate optical parametric amplifier, as
      predicted by Grangier et al. [Phys. Rev. A 38, 3132 (1988)]. The maximum observed
      visibility of the interference pattern was (89+/-4)%. This interference can be
      regarded as a manifestation of nonlocality in the sense described by Banaszek and
      Wodkiewicz [Phys. Rev. A 58, 4345 (1998)]. We have investigated the interference
      both theoretically and experimentally and have measured the influence of
      dispersion and phase matching.

PMID- 10970501
TI  - Two dimensional mechanism for insect hovering.
AB  - Resolved computation of two dimensional insect hovering shows for the first time
      that a two dimensional hovering motion can generate enough lift to support a
      typical insect weight. The computation reveals a two dimensional mechanism of
      creating a downward dipole jet of counterrotating vortices, which are formed from
      leading and trailing edge vortices. The vortex dynamics further elucidates the
      role of the phase relation between the wing translation and rotation in lift
      generation and explains why the instantaneous forces can reach a periodic state
      after only a few strokes. The model predicts the lower limits in Reynolds number
      and amplitude above which the averaged forces are sufficient.

PMID- 10970503
TI  - Classical and quantum interaction of the dipole
AB  - A unified and fully relativistic treatment of the interaction of the electric and
      magnetic dipole moments of a particle with the electromagnetic field is given.
      New forces on the particle due to the combined effect of electric and magnetic
      dipoles are obtained. Several new experiments are proposed, which include
      observation of topological phase shifts.

PMID- 10970504
TI  - How an anomalous cusp bifurcates in a weak-noise system
AB  - The pattern of activated trajectories in a symmetric double well system without
      detailed balance may contain cusps and other singularities, similar to the
      caustics of geometrical optics. We derive a scaling law and nonpolynomial
      "equations of state" that govern the bifurcation of an anomalous cusp (a cusp
      coinciding with the saddle) into conventional cusps. The bifurcation is reflected
      in the system quasipotential, much as a phase transition is reflected in the free
      energy of a thermodynamic system. The anomalous cusp is analogous to a
      nonclassical critical point. Besides showing how critical phenomena occur in
      noise-perturbed systems, our results extend classical catastrophe theory.

PMID- 10970505
TI  - 5-10 GeV neutrinos from gamma-Ray burst fireballs
AB  - A gamma-ray burst fireball is likely to contain an admixture of neutrons.
      Inelastic collisions between differentially streaming protons and neutrons in the
      fireball produce nu(&mgr;) (nu;(&mgr;)) of approximately 10 GeV as well as nu(e)
      (nu;(e)) of approximately 5 GeV, which could produce approximately 7 events/year
      in km(3) detectors, if the neutron abundance is comparable to that of protons.
      Photons of approximately 10 GeV from pi(0) decay and approximately 100 MeV nu;(e)
      from neutron decay are also produced, but will be difficult to detect. Photons
      with energies less, similar1 MeV from shocks following neutron decay produce a
      characteristic signal which may be distinguishable from the proton-related MeV
      photons.

PMID- 10970506
TI  - Characterizing the peak in the cosmic microwave background angular power spectrum
AB  - A peak has been unambiguously detected in the cosmic microwave background angular
      spectrum. Here we characterize its properties with fits to phenomenological
      models. We find that the TOCO and BOOM/NA data determine the peak location to be
      in the range 175-243 and 151-259, respectively (at 95% confidence) and determine
      the peak amplitude to be between approximately 70 and 90 &mgr;K. The peak shape
      is consistent with inflation-inspired flat, cold dark matter plus cosmological
      constant models of structure formation with adiabatic, nearly scale invariant
      initial conditions. It is inconsistent with open models and presents a great
      challenge to defect models.

PMID- 10970507
TI  - Primordial adiabatic fluctuations from cosmic defects
AB  - In the context of "two-metric" theories of gravity there is the possibility that
      cosmic defects will produce a spectrum of primordial adiabatic density
      perturbations, when the speed characterizing the defect-producing scalar field is
      much larger than the speed characterizing gravity and standard model particles.
      This model will exactly mimic the standard predictions of inflationary models,
      with the exception of a small non-Gaussian signal which could be detected by
      future experiments.

PMID- 10970508
TI  - Dual instantons
AB  - We show how to map the Belavin-Polyakov instantons of the O(3)-nonlinear sigma
      model to a dual theory where they then appear as nontopological solitons. They
      are stationary points of the Euclidean action in the dual theory, and moreover,
      the dual action and the O(3)-nonlinear sigma model action agree on shell.

PMID- 10970509
TI  - Limits on light gravitino production and new processes with large missing
      transverse energy in p&pmacr; collisions at sqrt
AB  - Events collected by the Collider Detector at Fermilab (CDF) with an energetic jet
      plus large missing transverse energy can be used to search for physics beyond the
      standard model. We see no deviations from the expected backgrounds and set upper
      limits on the production of new processes. We consider in addition the production
      of light gravitinos and set a limit at 95% confidence level on the breaking scale
      sqrt[F]>/=217 GeV, which excludes gravitino masses smaller than 1.1x10(-5)
      eV/c(2).

PMID- 10970510
TI  - Can cosmic strangelets reach the earth?
AB  - The mechanism for the propagation of strangelets with low baryon number through
      the atmosphere of the Earth has been explored. It has been shown that, under
      suitable initial conditions, such strangelets may indeed reach depths near
      mountain altitudes with mass numbers and charges close to the observed values in
      cosmic ray experiments.

PMID- 10970511
TI  - Quasifree compton scattering from the deuteron and nucleon polarizabilities
AB  - Cross sections for quasifree Compton scattering from the deuteron were measured
      for incident energies of E(gamma) = 236-260 MeV at the laboratory angle straight
      theta(gamma(')) = -135 degrees. The recoil nucleons were detected in a liquid
      scintillator array situated at straight theta(N) = 20 degrees. The measured
      differential cross sections were used, with the calculations of Levchuk et al.,
      to determine the polarizabilities of the bound nucleons. For the bound proton,
      the extracted values were consistent with the accepted value for the free proton.
      Combining our results for the bound neutron with those from Rose et al., we
      obtain 1-sigma constraints of alpha;(n) = 7.6-14.0 and beta;(n) = 1.2-7.6.

PMID- 10970512
TI  - First On-line beta-NMR on oriented nuclei: magnetic dipole moments of the
      (nup(1/2))(-1) 1/2(-) ground state in 67Ni and (pip(3/2))(+1) 3/2(-) ground state
      in 69Cu
AB  - The first fully on-line use of the angular distribution of beta emission in
      detection of NMR of nuclei oriented at low temperatures is reported. The magnetic
      moments of the single valence particle, intermediate mass, isotopes 67Ni(nup(
      1)(1/2);1/2(-)) and 69Cu(pip(1)(3/2);3/2(-)) are measured to be +0.601(5)
      &mgr;(N) and +2.84(1) &mgr;(N), respectively, revealing only a small deviation
      from the neutron p(1/2) single-particle value in the former and a large deviation
      from the proton p(3/2) single-particle value in the latter. Quantitative
      interpretation is given in terms of core polarization and meson-exchange
      currents.

PMID- 10970513
TI  - Robust nuclear observables and constraints on random interactions
AB  - The predictions of the interacting boson model two-body random ensemble are
      compared to empirical results on nuclei from Z = 8-100. Heretofore unrecognized
      but robust empirical trends are identified and related both to the distribution
      of valence nucleon numbers and to the need for and applicability of specific,
      nonrandom interactions. Applications to expected trends in exotic nuclei are
      discussed.

PMID- 10970514
TI  - Anharmonic properties of the double giant dipole resonance
AB  - A systematic microscopic study of the anharmonic properties of the double giant
      dipole resonance (DGDR) has been carried out, for the first time, for nuclei with
      mass number A spanning the whole mass table. It is concluded that the corrections
      of the energy centroid of the Jpi = 0(+) and 2(+) components of the DGDR from its
      harmonic limit are negative, have a value of the order of a few hundred keV, and
      follow an A-1 dependence.

PMID- 10970515
TI  - Coherent bremsstrahlung in the alpha + p system at 50 MeV/nucleon
AB  - Photons originating from coherent bremsstrahlung have been measured over a large
      dynamic range for the reaction of 200 MeV alpha particles with protons. At low
      photon energies the bremsstrahlung spectrum exhibits the classical behavior with
      an approximate 1/E(gamma) shape. At higher photon energies there is a pronounced
      contribution from capture into the unbound ground state and first excited state
      of 5Li. These results allow one, for the first time, to test theoretical models
      for a consistent description of bremsstrahlung and radiative capture in a complex
      system. Calculations predict both features qualitatively but fail to account for
      their relative importance.

PMID- 10970516
TI  - Photoassociative spectroscopy as a self-sufficient tool for the determination of
      the Cs triplet scattering length
AB  - In photoassociation spectroscopy, the line intensities of a given vibrational
      progression exhibit zero-signal modulation reflecting the node structure of the s
      wave ground state wave function of two free colliding atoms. This leads to the
      determination of the scattering length. We performed photoassociation of cold Cs
      atoms polarized in the Zeeman sublevel f = 4, m(f) = 4. We analyzed the
      intensities of the lines associated with the Cs2 0(-)(g) state dissociating to
      the 6s(1/2)+6p(3/2) asymptote. This yields a value of the Cs triplet state
      scattering length, a(T) = -530a(0), while consistency requirements impose a value
      of the multipole ground state molecular coefficient, C6 = 6510 a.u.

PMID- 10970517
TI  - Deformations and dilations of chaotic billiards: dissipation rate, and
      quasiorthogonality of the boundary wave functions
AB  - We consider chaotic billiards in d dimensions, and study the matrix elements
      M(nm) corresponding to general deformations of the boundary. We analyze the
      dependence of |M(nm)|(2) on omega = (E(n)-E(m))/Planck's over 2pi using
      semiclassical considerations. This relates to an estimate of the energy
      dissipation rate when the deformation is periodic at frequency omega. We show
      that, for dilations and translations of the boundary, |M(nm)|(2) vanishes like
      omega(4) as omega-->0, for rotations such as omega(2), whereas for generic
      deformations it goes to a constant. Such special cases lead to quasiorthogonality
      of the eigenstates on the boundary.

PMID- 10970518
TI  - Space intensity correlations in the near field of the scattered light: A direct
      measurement of the density correlation function g(r)
AB  - We show that the two point intensity correlation in the near field of the
      scattered light is directly related to the two point density correlation g(r).
      Preliminary measurements on two sets of calibrated random pinholes of 140 and 300
      &mgr;m diameters, and on aqueous solutions of latex spheres of 5, 10, and 40
      &mgr;m are reported. A discussion on the desirability of the technique as a
      simple and powerful alternative to low angle scattering will be presented.

PMID- 10970519
TI  - Bose-einstein partition statistics in superradiant spontaneous emission
AB  - We report the realization of the spatial counterpart of the Dicke superradiance.
      The new process is revealed by the realization of the spatial quantum partition
      statistics within the detection of photons emitted in sub-Poissonian regime by an
      active microcavity excited by ultrashort pulses. The superradiant enhancement of
      the time decay of the dipole excitation has also been investigated.

PMID- 10970520
TI  - Observation of dipole-mode vector solitons
AB  - We report on the first experimental observation of a novel type of optical vector
      soliton, a dipole-mode soliton, recently predicted theoretically. We show that
      these vector solitons can be generated in a photorefractive medium employing two
      different processes: a phase imprinting, and a symmetry-breaking instability of a
      vortex-mode vector soliton. The experimental results display remarkable agreement
      with the theory, and confirm the robust nature of these radially asymmetric two
      component solitary waves.

PMID- 10970521
TI  - Particle dynamics in sheared granular matter
AB  - The particle dynamics and shear forces of granular matter in a Couette geometry
      are determined experimentally. The normalized tangential velocity V(y) declines
      strongly with distance y from the moving wall, independent of the shear rate and
      of the shear dynamics. Local rms velocity fluctuations deltaV(y) scale with the
      local velocity gradient to the power 0.4+/-0.05. These results agree with a
      locally Newtonian, continuum model, where the granular medium is assumed to
      behave as a liquid with a local temperature [deltaV(y)](2) and density dependent
      viscosity.

PMID- 10970522
TI  - Enhanced instability in thin liquid films by improved compatibility
AB  - We investigated experimentally the morphological evolution of thin
      polydimethylsiloxane films sandwiched between a silicon wafer and different
      bounding liquids with interfacial tensions varying by 2 orders of magnitude. It
      is shown that increasing the compatibility between film and bounding liquid by
      adding a few surfactant molecules results in a faster instability of shorter
      characteristic wavelength. Inversely, based on the characteristic parameters
      describing the instability we determined extremely small interfacial tensions
      with a remarkable accuracy.

PMID- 10970523
TI  - Shear effects in nonhomogeneous turbulence
AB  - Motivated by recent experimental and numerical results, a simple unifying picture
      of intermittency in turbulent shear flows is suggested. Integral structure
      functions (ISF), taking into account explicitly the shear intensity, are
      introduced on phenomenological grounds. ISF can exhibit a universal scaling
      behavior, independent of the shear intensity. This picture is in satisfactory
      agreement with both experimental and numerical data. Possible extension to
      convective turbulence and implication on closure conditions for large-eddy
      simulation of nonhomogeneous flows are briefly discussed.

PMID- 10970524
TI  - Plasma line emission from short pulse laser interactions with dense plasmas
AB  - Plasma line emission is observed in simulations of dense plasma irradiated by
      moderately intense light pulses of duration some tens of femtoseconds, and its
      scaling with density and with laser intensity is studied. Plasma emission is
      recorded both during the pulse where it is observed against the background
      spectrum of harmonics of the laser frequency as well as postpulse. Harmonics of
      the plasma line up to the fifth have been observed. An unexpected feature present
      in most of the reflected light spectra appears on the blue side of the plasma
      line with a central frequency omega approximately 1.5omega(p).

PMID- 10970525
TI  - Enhanced confinement and stability of a field-reversed configuration with
      rotating magnetic field current drive
AB  - A new experiment has been constructed to study the sustainment of a field
      reversed configuration (FRC) with a rotating magnetic field (RMF). FRCs were
      formed with cold, unmagnetized ions and thus without a kinetic ion component that
      was believed to provide stability to internal tilt modes. No destructive
      instabilities were observed for the RMF FRC. Only peripheral radial penetration
      of the RMF was observed. The radially inward flow arising from axial screening
      currents at the FRC edge reduced convective and conductive losses to the
      measurement limit of the diagnostics.

PMID- 10970526
TI  - Coulomb explosion patterns of fast C60 clusters in solids
AB  - The molecular dynamics method is used to simulate Coulomb explosion of fast C60
      ion clusters in an Al target, taking into account dynamical screening of
      interionic interactions by the electron gas of the target. It is found that the
      wake forces in the medium are strong enough, depending on cluster speed, to
      stabilize the whole cluster against Coulomb explosion, or to compress the
      trailing part of the cluster, for prolonged times of penetration through the
      target. This is encouraging news for such cluster-ion beams applications where
      massive energy depositions in small volumes of targets are desired.

PMID- 10970527
TI  - Vibrational lifetime of bond-center hydrogen in crystalline silicon
AB  - The lifetime of the stretch mode of bond-center hydrogen in crystalline silicon
      is measured to be T1 = 7.8+/-0.2 ps with time-resolved, transient bleaching
      spectroscopy. The low-temperature spectral width of the absorption line due to
      the stretch mode converges towards its natural width for decreasing hydrogen
      concentration C(H), and nearly coincides with the natural width for C(H)
      approximately 1 ppm. The lifetimes of the Si-H stretch modes of selected hydrogen
      related defects are estimated from their spectral widths and shown to range from
      1.6 to more than 37 ps.

PMID- 10970528
TI  - Investigation of the radial deformability of individual carbon nanotubes under
      controlled indentation force
AB  - Tapping-mode atomic force microscopy was used to study the radial deformability
      of a multiwalled carbon nanotube (MWCNT). By imaging the MWCNT under different
      tapping forces, we were able to demonstrate its remarkable reversible radial
      deformability (up to approximately 40%) and reveal internal discontinuities along
      its length. The values of the effective elastic modulus of several sections of
      the MWCNT in the radial direction were estimated with the Hertz model.

PMID- 10970529
TI  - Phonons in an entropic crystal
AB  - Hard spheres crystallize due to purely entropic forces. The underlying excluded
      volume interaction is completely anharmonic and the nature of the phonon spectrum
      is therefore of interest. To measure the single-particle motion and the phonon
      spectrum by dynamic light scattering we have used a collection of novel
      techniques including multispeckle cross correlation on a CCD chip and the growth
      of large single crystals using a temperature gradient. The random hexagonal close
      packed crystal has a dispersion relation closer to hcp than to fcc.

PMID- 10970530
TI  - Role of unstable directions in the equilibrium and aging dynamics of supercooled
      liquids
AB  - The connectivity of the potential energy landscape in supercooled atomic liquids
      is investigated through a calculation of the instantaneous normal modes spectrum
      and a detailed analysis of the unstable directions in configuration space. We
      confirm the hypothesis that the mode-coupling critical temperature is the T at
      which the dynamics crosses over from free to activated exploration of
      configuration space. We also observe changes in the local connectivity of
      configuration space sampled during aging, following a temperature jump from a
      liquid to a glassy state.

PMID- 10970531
TI  - 3He spin diffusion measurements in 3He- 4He mixture films
AB  - 3He spin diffusion measurements for 3He-4He mixture films on Nuclepore are
      reported as a function of 3He coverage for 0. 030</=T</=0.070 K. We report
      measurements for a constant 4He coverage of 5.0 bulk density atomic layers, with
      3He coverages between 0.10 and 0.98 layers. We find that the 3He spin diffusion
      coefficient, as measured by Hahn spin echoes, has an unexplained maximum as a
      function of 3He coverage and that the temperature dependence is somewhat weaker
      than predicted. Comparison measurements are presented for the NMR relaxation
      times T1 and T2 and the magnetization over the same 3He coverage range.

PMID- 10970532
TI  - Stability of inverse bicontinuous cubic phases in lipid-water mixtures
AB  - We investigate the stability of seven inverse bicontinuous cubic phases [ G, D,
      P, C(P), S, I-WP, F-RD] in lipid-water mixtures based on a curvature model of
      membranes. Lipid monolayers are described by parallel surfaces to triply periodic
      minimal surfaces. The phase behavior is determined by the distribution of the
      Gaussian curvature on the minimal surface and the porosity of each structure.
      Only G, D, and P are found to be stable, and to coexist along a triple line. The
      calculated phase diagram agrees very well with experimental results for 2:1
      lauric acid/DLPC.

PMID- 10970533
TI  - Alignment of hexatic langmuir monolayers under shear.
AB  - We have studied the structural changes that fatty acid monolayers in the Ov phase
      undergo when a simple shear flow is imposed. A strong coupling is revealed by the
      changes in domain structure that are observable using Brewster angle microscopy,
      suggesting the possibility of shear alignment. The dependence of the alignment on
      the molecular polar tilt proves that the mechanism is different than in nematic
      liquid crystals. We argue that the degenerate lattice symmetry lines of the
      underlying pseudohexagonal lattice align in the flow direction, and we explain
      the observed alignment angle using geometrical arguments.

PMID- 10970534
TI  - Determination of interlayer diffusion parameters for Ag/Ag(111)
AB  - It is well known that the Ag/Ag(111) epitaxial system grows three dimensionally
      because of the existence of a relatively high excess diffusion barrier, DeltaE(s)
      = 0.13 eV, at the step edges. Several experimental methods have been developed to
      measure the step edge barrier in this system over a wide coverage range. The
      probability for an atom to move from a higher to a lower layer depends on both
      the barrier and the prefactor, so it is important to test whether the prefactors
      for hopping over a step, nu(s), and for hopping on a terrace, nu(t), are
      different. We present the results from several experiments on Ag/Ag(111) to
      conclude that nu(s)/nu(t) = 10(2.0+/-0. 3).

PMID- 10970535
TI  - Superheating of confined Pb thin films
AB  - In this work we report, for the first time, an experimental observation of a
      superheating phenomenon in metal thin films. By means of cold rolling, Pb thin
      films of about 20 nm thick were sandwiched by Al layers, and between them
      semicoherent epitaxial Pb/Al interfaces were formed. In situ x-ray diffraction
      analysis indicated that the confined Pb thin films could be superheated for at
      least 6 degrees C. Thermodynamic analysis indicated that such a substantial
      superheating in the confined two-dimensional thin films may originate from
      suppression of growth of the molten droplets by the epitaxial Al/Pb/Al
      confinement, instead of suppression of melt nucleation for the confined particle
      superheating.

PMID- 10970536
TI  - Anomalous mobility of strongly bound surface species: Cl on GaAs(001)-c(8 x 2)
AB  - Although strongly bound chemisorbates at low coverage readily diffuse on metal
      surfaces at 300 K, they generally do not diffuse on semiconductor surfaces
      because of a large corrugation in the adsorbate-surface interaction potential.
      Chlorine chemisorbed on the Ga-rich GaAs(001)-c(8x2) surface has anomalously fast
      diffusion even though the chemisorption state is tightly bound and highly
      specific. Simple Hartree-Fock total energy calculations suggest that this
      diffusion of strongly bound adsorbates can occur at 300 K because there are
      multiple nearly degenerate adsorbate sites.

PMID- 10970537
TI  - Self-limiting growth of metal fluoride thin films by oxidation reactions
      employing molecular precursors
AB  - FeF (2) films are grown by the reaction of XeF (2) and SeF (6) with iron foil.
      The growth initially follows the Mott-Cabrera parabolic rate law, indicating that
      the process is diffusion limited. At a certain film thickness, however, the
      growth abruptly stops, with the thickness using XeF (2) being nearly double that
      with SeF (6). It is suggested that the shutdown is due to the inability of the
      molecules to dissociate when too far from the substrate and that SeF (6) must
      approach more closely than XeF (2). This work suggests the use of molecular
      precursors to grow thin films via a self-limiting chemical process.

PMID- 10970538
TI  - n--> infinity limit of O(n) ferromagnetic models on graphs
AB  - Thirty years ago, H. E. Stanley showed that an O(n) spin model on a lattice tends
      to a spherical model as n-->infinity. This means that at any temperature the
      corresponding free energies coincide. This fundamental result is no longer valid
      on more general discrete structures lacking in translation invariance, i.e., on
      graphs. However, only the singular parts of the free energies determine the
      critical behavior of the two statistical models. Here we show that for
      ferromagnetic models such singular parts still coincide even on graphs in the
      thermodynamic limit. This implies that the critical exponents of O(n) models on
      graphs for n-->infinity tend to the spherical ones and depend only on the graph
      spectral dimension.

PMID- 10970539
TI  - Magnetic breakdown at high fields: semiclassical and quantum treatments
AB  - The effects of finite temperature and noninteracting spins on magnetic breakdown
      (MB) in a quasi-two-dimensional organic conductor have been determined by
      computing the field-dependent free energy using a realistic crystal structure
      with no adjustable parameters. The de Haas-van Alphen oscillation spectra,
      including the MB phenomena, are thereby obtained microscopically. Within the
      range of computed magnetic field, from 170 to 1400 T, we find remarkable
      agreement between the predictions of the semiclassical and quantum treatment. We
      also find that the Zeeman effect leads to splitting of a frequency corresponding
      to the fundamental orbit.

PMID- 10970540
TI  - Kondo effect in a magnetic field and the magnetoresistivity of kondo alloys
AB  - The effect of a magnetic field on the spectral density of a S = 1/2 Kondo
      impurity is investigated at zero and finite temperatures by using Wilson's
      numerical renormalization group method. A splitting of the total spectral density
      is found for fields larger than a critical value H(c)(T = 0) approximately
      0.5T(K), where T(K) is the Kondo scale. The splitting correlates with a peak in
      the magnetoresistivity of dilute magnetic alloys which we calculate and compare
      with the experiments on CexLa1-xAl2,x = 0.0063. The linear magnetoconductance of
      quantum dots exhibiting the Kondo effect is also calculated.

PMID- 10970541
TI  - Generalized numerical renormalization group for dynamical quantities
AB  - In this paper we introduce a new approach for calculating dynamical properties
      within the numerical renormalization group. It is demonstrated that the method
      previously used fails for the Anderson impurity in a magnetic field due to the
      absence of energy scale separation. The problem is solved by evaluating the Green
      function with respect to the reduced density matrix of the full system, leading
      to accurate spectra in agreement with the static magnetization. The new procedure
      provides a unifying framework for calculating dynamics at any temperature and
      represents the correct extension of Wilson's original thermodynamic calculation.

PMID- 10970542
TI  - Photogalvanic effects in heteropolar nanotubes
AB  - We show that an electrical shift current is generated when electrons are
      photoexcited from the valence to conduction bands on a BN nanotube. This
      photocurrent follows the light pulse envelope and its symmetry is controlled by
      the atomic structure of the nanotube. We find that the shift current has an
      intrinsic quantum mechanical signature in which the chiral index of the tube
      determines the direction of the current along the tube axis. We identify the
      discrete lattice effects in the tangent plane of the tube that lead to an
      azimuthal component of the shift current. The nanotube shift current can lead to
      ultrafast optoelectronic and optomechanical applications.

PMID- 10970544
TI  - Electron and hole focusing in CoSi2/Si(111) observed by ballistic electron
      emission microscopy
AB  - In ballistic electron emission microscopy (BEEM) the propagation of hot carriers
      in thin metal films has long been treated using a free electron model. While the
      model explains many experimental findings, it cannot account for the lateral
      resolution observed for both electrons and holes on epitaxial CoSi(2)/Si(111),
      where interfacial point defects of atomic size appear as small as 1.3 nm, even
      below a 5.6 nm thick film. We present ab initio calculations explaining this high
      resolution in terms of conduction (valence) band structure focusing of electrons
      (holes), according to a recent Green's function approach to the BEEM process.

PMID- 10970543
TI  - Dephasing times in quantum dots due to elastic LO phonon-carrier collisions
AB  - Interpretation of experiments on quantum dot (QD) lasers presents a challenge:
      the phonon bottleneck, which should strongly suppress relaxation and dephasing of
      the discrete energy states, often seems to be inoperative. We suggest and develop
      a theory for an intrinsic mechanism for dephasing in QDs: second-order elastic
      interaction between quantum dot charge carriers and LO phonons. The calculated
      dephasing times are of the order of 200 fs at room temperature, consistent with
      experiments. The phonon bottleneck thus does not prevent significant room
      temperature dephasing.

PMID- 10970545
TI  - d-wave superconductivity in the hubbard model
AB  - The superconducting instabilities of the doped repulsive 2D Hubbard model are
      studied in the intermediate to strong coupling regime with the help of the
      dynamical cluster approximation. To solve the effective cluster problem we employ
      an extended noncrossing approximation, which allows for a transition to the
      broken symmetry state. At sufficiently low temperatures we find stable d-wave
      solutions with off-diagonal long-range order. The maximal T(c) approximately 150
      K occurs for a doping delta approximately 20% and the doping dependence of the
      transition temperatures agrees well with the generic high- T(c) phase diagram.

PMID- 10970546
TI  - Fine structure in magnetization of individual fluxoid states
AB  - Each time a vortex enters or exits a small superconductor, a different fluxoid
      state develops which can be characterized by its vorticity, i.e., the number of
      fluxoids inside. We have studied magnetization response of such individual states
      and found clear signatures of first and second order transitions within the
      states, which reveal the existence of distinct vortex phases for a fixed number
      of fluxoids. We attribute the transitions to the merger of individual vortices
      into a single giant vortex and switching between different arrays of vortices.

PMID- 10970547
TI  - Zero-temperature d-wave superconducting phase transition
AB  - The Ginzburg-Landau-Wilson theory that describes the disordered-metal- d-wave
      superconductor phase transition at zero temperature is derived at weak coupling.
      The theory represents an interacting dissipative system of bosonic Cooper pairs
      in an effective random potential. I show that there exists a wide crossover
      regime in the theory controlled by a line of Gaussian fixed points, each of which
      in two dimensions is characterized by a different universal value of the dc
      critical conductivity. Relation to experiments on overdoped and underdoped
      cuprates is discussed.

PMID- 10970548
TI  - STM studies of the electronic structure of vortex cores in
      Bi(2)Sr(2)CaCu(2)O(8+delta)
AB  - We report on low temperature scanning tunneling microscopy (STM) studies of the
      electronic structure of vortex cores in Bi 2Sr 2CaCu 2O (8+delta). At the vortex
      core center, an enhanced density of states is observed at energies near Omega =
      +/-7 meV. Spectroscopic imaging at these energies reveals an exponential decay of
      these "core states" with a decay length of 22+/-3 A. The fourfold symmetry
      sometimes predicted for d-wave vortices is not seen in spectroscopic vortex
      images. A locally nodeless order parameter induced by the magnetic field may be
      consistent with these measurements.

PMID- 10970550
TI  - Squeezing of nitrogen atomic orbitals in a chemical trap
AB  - Fullerenes can act as inert cages for highly reactive nitrogen atoms even at room
      temperature. Confinement in a cage of less than spherical symmetry as realized in
      C70 leads to a characteristic deformation of the atomic charge and spin
      distributions which can be sensed by magnetic resonance techniques. A
      quantitative analysis of the amount of orbital squeezing is possible by
      comparison with data of free nitrogen ions.

PMID- 10970549
TI  - Low temperature limit of the vortex core radius and the kramer-pesch effect in
      NbSe2
AB  - Muon spin rotation ( &mgr;SR) has been used to measure the magnetic field
      distribution in the vortex state of the type-II superconductor NbSe2 ( T(c) = 7.0
      K) below T = 2 K. The distribution is consistent with a highly ordered hexagonal
      vortex lattice with a well resolved high-field cutoff associated with the finite
      size of the vortex cores. The temperature dependence of the core radius is much
      weaker than the temperature dependence predicted from the Bogoliubov-de Gennes
      theory. Furthermore, the vortex radius measured by &mgr;SR near the low
      temperature quantum limit is about an order of magnitude larger than predicted.

PMID- 10970551
TI  - Near-field spectral effects due to electromagnetic surface excitations
AB  - We demonstrate theoretically that the spectra of electromagnetic emission of
      surface systems can display remarkable differences in the near and the far zones.
      The spectral changes occur due to the loss of evanescent modes and are especially
      pronounced for systems which support surface waves.

PMID- 10970552
TI  - Interaction of localized electronic states with the conduction band: band
      anticrossing in II-VI semiconductor ternaries
AB  - We report a strongly nonlinear pressure dependence of the band gaps and large
      downward shifts of the conduction band edges as functions of composition in ZnS
      xTe (1-x) and ZnSe (y)Te (1-y) alloys. The dependencies are explained by an
      interaction between localized A1 symmetry states of S or Se atoms and the
      extended states of the ZnTe matrix. These results, combined with previous studies
      of III-N-V materials define a new, broad class of semiconductor alloys in which
      the introduction of highly electronegative atoms leads to dramatic modifications
      of the conduction band structure. The modifications are well described by the
      recently introduced band anticrossing model.

PMID- 10970553
TI  - Non-lorentzian single-molecule line shape: pseudolocal phonons and coherence
      transfer
AB  - The excitation line shape of a single terrylene molecule in a naphthalene crystal
      has been investigated. In addition to the conventional Lorentzian, it consists of
      a dispersive component in the core region and a sideband. This is due to a
      pseudolocal phonon caused by the substitution of a host molecule with the
      chromophore. When the pseudolocal phonon is excited, the resonance frequency of
      the chromophore slightly changes, resulting in the appearance of a second,
      quasiresonant transition. Coherence transfer between these two optical
      transitions causes the deviation from the purely Lorentzian line shape.

PMID- 10970554
TI  - Generalized schmidt decomposition and classification of three-quantum-Bit states
AB  - We prove for any pure three-quantum-bit state the existence of local bases which
      allow one to build a set of five orthogonal product states in terms of which the
      state can be written in a unique form. This leads to a canonical form which
      generalizes the two-quantum-bit Schmidt decomposition. It is uniquely
      characterized by the five entanglement parameters. It leads to a complete
      classification of the three-quantum-bit states. It shows that the right outcome
      of an adequate local measurement always erases all entanglement between the other
      two parties.

PMID- 10970555
TI  - Charge transport along the lambda-DNA double helix.
AB  - We have measured the conductivity sigma along the lambda phage DNA (lambda-DNA)
      double helix at microwave frequencies using lyophilized DNA in and also without a
      buffer. The conductivity is strongly temperature dependent around room
      temperature with a crossover to a weakly temperature dependent conductivity at
      low temperatures. Removal of the water mantle around the double helix leads to
      reduced conductivity.

PMID- 10970556
TI  - Macroions in salty water with multivalent ions: giant inversion of charge
AB  - Screening of a strongly charged macroion by oppositely charged colloidal
      particles, micelles, or short polyelectrolytes is considered. Because of strong
      lateral repulsion such multivalent counterions form a strongly correlated liquid
      at the surface of the macroion. This liquid provides correlation-induced
      attraction of multivalent counterions to the macroion surface. As a result even a
      moderate concentration of multivalent counterions in the solution inverts the
      sign of the net macroion charge. We show that at high concentration of monovalent
      salt the absolute value of inverted charge can be larger than the bare one. This
      giant inversion of charge can be observed in electrophoresis.

PMID- 10970557
TI  - Pulling pinned polymers and unzipping DNA.
AB  - We study a class of micromanipulation experiments, exemplified by the pulling
      apart of the two strands of double-stranded DNA. When the pulling force is
      increased to a critical value, an "unzipping" transition occurs. For random DNA
      sequences with short-ranged correlations, we obtain exact results for the number
      of monomers liberated and the specific heat, including the critical behavior at
      the transition. Related systems include a random heteropolymer pulled away from
      an adsorbing surface and a vortex line in a type II superconductor tilted away
      from a fragmented columnar defect.

PMID- 10970558
TI  - Suprathreshold stochastic firing dynamics with memory in P-type electroreceptors.
AB  - Weakly electric fish generate a periodic electric field as a carrier signal for
      active location and communication tasks. Highly sensitive P-type receptors on
      their surface fire in response to carrier amplitude modulations (AM's) in a noisy
      phase locked fashion. A simple generic model of receptor activity and signal
      encoding is presented. Its suprathreshold dynamics, memory and receptor noise
      reproduce observed firing interval distributions and correlations. The model
      ultimately explains how smooth responses to AM's are compatible with its
      nonlinear phase locking properties, and reveals how receptor noise can sometimes
      enhance the encoding of small yet suprathreshold AM's.

PMID- 10970559
TI  - Failure of 1D models for Ir island diffusion on Ir(111)

PMID- 10970560
TI  - Krylov replies:

PMID- 10970561
TI  - Comment on "Mystery of the alkali metals: giant moments of Fe and Co on and in Cs
      films"

PMID- 10970563
TI  - Beckmann and bergmann reply:

PMID- 10970562
TI  - Comment on "Mystery of the alkali metals: giant moments of Fe and Co on and in Cs
      films"

PMID- 10970564
TI  - Geometric phases and multiple degeneracies in harmonic resonators
AB  - In a recent experiment Lauber et al. have deformed cyclically a microwave
      resonator and have measured the adiabatic normal-mode wave functions for each
      shape along the path of deformation. The nontrivial observed cyclic phases around
      a threefold degeneracy were accounted for by Manolopoulos and Child within an
      approximate theory. However, open-path geometrical phases disagree with
      experiment. By solving exactly the problem, we find unsuspected extra
      degeneracies around the multiple one that account for the measured phase changes
      throughout the path. It turns out that proliferation of additional degeneracies
      around a multiple one is a common feature of quantum mechanics.

PMID- 10970565
TI  - Renormalization of the inverse square potential
AB  - The quantum-mechanical D-dimensional inverse square potential is analyzed using
      field-theoretic renormalization techniques. A solution is presented for both the
      bound-state and scattering sectors of the theory using cutoff and dimensional
      regularization. In the renormalized version of the theory, there is a strong
      coupling regime where quantum-mechanical breaking of scale symmetry takes place
      through dimensional transmutation, with the creation of a single bound state and
      of an energy-dependent s-wave scattering matrix element.

PMID- 10970566
TI  - Generation of spin squeezing via continuous quantum nondemolition measurement
AB  - Continuous quantum nondemolition monitoring of a collective atomic spin with an
      off-resonant laser beam has been performed. Squeezed atomic spin states have
      thereby been produced with spin noise reduction to 70% below the standard quantum
      limit expected for a coherent spin state.

PMID- 10970567
TI  - Motional dressed states in a bose-einstein condensate: superfluidity at
      supersonic speed
AB  - We present an exact analytic solution of a nonlinear Schrodinger field
      interacting with a moving potential (obstacle) at supersonic speed. We discover
      conditions under which the field can form a stable shape-invariant structure
      localized around the obstacle-a dressing effect that protects the field against
      excitations by the obstacle. Such an effect demonstrates the existence of
      frictionless motion beyond the conventionally defined critical velocity.

PMID- 10970568
TI  - Particles sliding on a fluctuating surface: phase separation and power laws
AB  - We study a system of hard-core particles sliding locally downwards on a
      fluctuating one-dimensional surface characterized by a dynamical exponent z and
      no overall tilt. In numerical simulations, an initially random particle density
      is found to coarsen and obey scaling with a growing length scale approximately
      t(1/z). The structure factor deviates from the Porod law for the models studied.
      The steady state is unusual in that the density-segregation order parameter shows
      strong fluctuations. The two-point correlation function has a scaling form with a
      cusp at small argument which we relate to a power law distribution of particle
      cluster sizes. Exact results on a related model of surface depths provide insight
      into this behavior.

PMID- 10970569
TI  - Entropy production, fractals, and relaxation to equilibrium
AB  - The theory of entropy production in nonequilibrium, Hamiltonian systems,
      previously described for steady states using partitions of phase space, is here
      extended to time dependent systems relaxing to equilibrium. We illustrate the
      main ideas by using a simple multibaker model, with some nonequilibrium initial
      state, and we study its progress toward equilibrium. The central results are (i)
      the entropy production is governed by an underlying, exponentially decaying
      fractal structure in phase space, (ii) the rate of entropy production is largely
      independent of the scale of resolution used in the partitions, and (iii) the rate
      of entropy production is in agreement with the predictions of nonequilibrium
      thermodynamics.

PMID- 10970570
TI  - Probable values of the cosmological constant in a holographic theory
AB  - We point out that for a large class of universes, holography implies that the
      most probable value for the cosmological constant is zero. In four space-time
      dimensions, the probability distribution takes the Baum-Hawking form, dP
      approximately exp(cM(2)(p)/Lambda)dLambda.

PMID- 10970571
TI  - Spontaneous symmetry breaking at infinite momentum without P+ zero modes
AB  - The nonrelativistic interpretation of quantum field theory achieved by
      quantization in an infinite momentum frame is spoiled by the inclusion of a mode
      of the field carrying p(+) = 0. We therefore explore the viability of doing
      without such a mode in the context of spontaneous symmetry breaking (SSB), where
      its presence would seem to be most needed. We show that the physics of SSB in
      scalar quantum field theory in 1+1 space-time dimensions is accurately described
      without a zero mode.

PMID- 10970572
TI  - Reconciliation of the measurement of parity nonconservation in Cs with the
      standard model
AB  - Contributions from the Breit interaction in atomic structure calculations account
      for 1.3sigma of the previously reported 2. 5sigma deviation from the standard
      model in the 133Cs weak charge [S. C. Bennett and C. E. Wieman, Phys. Rev. Lett.
      82, 2484 (1999)]. The updated corrections for the neutron distribution reduce the
      discrepancy further to 1.0sigma. The updated value of the weak charge is
      Q(W)(133Cs) = -72.65(28)(expt)(34)(theor).

PMID- 10970573
TI  - Measurement and cancellation of the cold collision frequency shift in an 87Rb
      fountain clock
AB  - We measure a cold collision frequency shift in an 87Rb fountain clock that is
      fractionally 30 times smaller than that for Cs. The shift is -0.38(8) mHz for a
      density of 1.0(6)x10(9) cm(-3). We study the cavity pulling of the atomic
      transition and use it to cancel the cold collision shift. We also measure the
      partial frequency shifts of each clock state finding 2(lambda(10)
      lambda(20))/(lambda(10)+lambda(20)) = 0.1(6).

PMID- 10970574
TI  - Steering an eigenstate to a destination
AB  - The control of time evolution of a quantum state under various physical
      constraints is investigated and solved in the context of a two-level system. We
      have discovered a general scheme of steering an eigenenergy state to a
      destination without net nonadiabatic transitions, and we discuss how the result
      may be tested and utilized in practice.

PMID- 10970575
TI  - Selection rules and isotope effects in the full fragmentation of the hydrogen
      molecule
AB  - Selection rules predicting zeros in cross sections for full fragmentation of the
      hydrogen molecule into specific momentum configurations are presented. Isotope
      effects are predicted to arise from these selection rules and from the correlated
      motion of nuclei and electrons in the final state.

PMID- 10970576
TI  - Electrons ejected with half the projectile velocity and the saddle point
      mechanism in ion-atom collisions
AB  - Full three-dimensional ejected electron momentum distributions for proton impact
      ionization of atomic hydrogen are calculated for impact energies 10 through 50
      keV. The distributions show a peak in the longitudinal momentum at half the
      projectile impact velocity: the v/2 peak. A quantitative assessment of saddle
      point ionization, based on quantum and classical analysis, reveals that the v/2
      peak is a false indicator for this mechanism. The influence of the potential
      saddle on ionization is seen to decrease rapidly from 10 to 50 keV.

PMID- 10970577
TI  - Spin anisotropy for excitation in collisions between two one-electron atoms
AB  - The singlet and triplet contributions of excitation cross sections are studied
      theoretically for collisions between various two one-electron atoms. The spin
      anisotropy is shown to have a general behavior in the important impact energy
      range. At low energies triplet cross sections dominate completely over the
      singlet ones while the opposite is true when the active electron and projectile
      velocities are comparable. Beyond the matching velocity regime singlet and
      triplet contributions become identical. We propose a general dynamical
      interpretation based on the analysis of the time dependency of the electron
      probability density and probability current density.

PMID- 10970578
TI  - Resonant formation of d&mgr;t molecules in deuterium: An atomic beam measurement
      of muon catalyzed dt fusion
AB  - Resonant formation of d&mgr;t molecules in collisions of muonic tritium ( &mgr;t)
      on D2 was investigated using a beam of &mgr;t atoms, demonstrating a new direct
      approach in muon catalyzed fusion studies. Strong epithermal resonances in
      d&mgr;t formation were directly revealed for the first time. From the time-of
      flight analysis of 2036+/-116 dt fusion events, a formation rate consistent with
      0.73+/-(0.16)(meas)+/-(0.09)(model) times the theoretical prediction was
      obtained. For the largest peak at a resonance energy of 0.423+/-0.037 eV, this
      corresponds to a rate of (7.1+/-1.8)x10(9) s(-1), more than an order of magnitude
      larger than those at low energies.

PMID- 10970579
TI  - Thermoacoustic separation of a He-Ar mixture
AB  - We report observation of a new mixture-separation process: an insonified mixture
      of helium and argon in a narrow duct spatially separates along the acoustic
      propagation axis. We measure mole-fraction differences across the ends of the
      duct as large as 7%. We measure initial separation flux densities as high as 10(
      3) M2 c, where M is the acoustic Mach number and c is the sound speed. This
      initial separation flux, as a function of both the amplitudes and the relative
      phasing of the pressure and velocity oscillations in the duct, agrees well with a
      recent theory involving oscillating thermal diffusion in the acoustic boundary
      layer.

PMID- 10970580
TI  - Experimental studies on long-wavelength instability and spiral breakup in a
      reaction-diffusion system
AB  - We investigate the behavior of spiral waves in a quasi-two-dimensional spatial
      open reactor using Belousov-Zhabotinsky reaction. The goal of this study is to
      answer two questions raised recently: Can a system sustain a stable long
      wavelength modulated spiral? What causes the transition from spiral to defect
      mediated turbulence? Our experimental results show that in a certain range of
      control parameters, a sustained long-wavelength modulated spiral is stable. The
      amplitude and the wavelength of modulations increase with the control parameter.
      As the latter is increased to across a threshold, defects are generated far away
      from the spiral center as a result of the neighboring two wave fronts being too
      close.

PMID- 10970581
TI  - Energetic heavy-Ion and proton generation from ultraintense laser-plasma
      interactions with solids
AB  - Heavy ions with energies up to 430+/-40 MeV have been measured from laser-solid
      interactions at focused intensities of up to 5x10(19) W/cm(2). Observations of
      proton emission indicate significant structure in the energy spectrum as well as
      an angular emission profile which varies with energy. Two qualitatively different
      components of ion emission are observed: (i) a high-energy component which is
      likely generated by a combination of "Coulomb explosion" and acceleration by the
      space charge force from hot electrons which escape the plasma, and (ii) a lower
      energy component which forms a ring likely created by magnetic fields in the
      ablated plasma.

PMID- 10970582
TI  - Enhanced forward scattering in the case of two crossed laser beams interacting
      with a plasma
AB  - The nonlinear enhancement of large-angle forward scattering of two identical
      laser beams propagating in a preformed plasma has been observed experimentally.
      The spectral analysis of the forward-scattered light shows two components, one
      which is unshifted with respect to the initial laser light frequency, and the
      other which is redshifted by a few angstroms. The redshifted component is found
      to be strongly enhanced in the case of crossed beam interaction in comparison
      with that of one beam illumination. Two-dimensional numerical simulations show
      that this enhancement is due to large-angle forward stimulated Brillouin
      scattering in which each beam serves as seed for the forward scattering of the
      other.

PMID- 10970583
TI  - Quasi-single-helicity reversed-field-pinch plasmas
AB  - The reversed field pinch (RFP) is a configuration for plasma magnetic
      confinement. It has been traditionally viewed as dominated by a bath of MHD
      instabilities producing magnetic chaos and high energy transport. We report
      experimental results which go beyond this view. They show a decrease of magnetic
      chaos and the formation of a coherent helical structure in the plasma, whose
      imaging and temperature profile are provided for the first time. These quasi
      single-helicity states are observed both transiently and in stationary
      conditions. The last case is consistent with a theoretically predicted
      bifurcation. Our results set a new frame for improving confinement in high
      current nonchaotic RFP's.

PMID- 10970585
TI  - Critical behavior of layer compression modulus near the smectic- A-smectic-
      C(*)(alpha) transition
AB  - The layer compression modulus was measured near the smectic- A-smectic-
      C(*)(alpha) phase transition in a chiral smectic liquid crystal. The layer
      compression modulus B shows marked pretransitional effects above the phase
      transition. The critical softening of B can be fit to a simple power law. It is
      described by the theoretical description based on the renormalization-group
      method and seems to suggest a crossover behavior. These effects clearly show that
      the transition is not of the Landau mean-field type.

PMID- 10970584
TI  - Spectroscopic evidence for the tricapped trigonal prism structure of
      semiconductor clusters
AB  - We have obtained photoelectron spectra (PES) for silicon cluster anions with up
      to 20 atoms. Efficient cooling of species in the source has allowed us to resolve
      multiple features in the PES for all sizes studied. Spectra for an extensive set
      of low-energy Si(-)(n) isomers found by a global search have been simulated using
      density functional theory and pseudopotentials. Except for n = 12, calculations
      for Si(-)(n) ground states agree with the measurements. This does not hold for
      other plausible geometries. Hence PES data validate the tricapped trigonal prism
      morphologies for medium-sized Si clusters.

PMID- 10970586
TI  - High resolution transmission electron microscopy observation of thermally
      fluctuating phasons in decagonal Al-Cu-Co
AB  - In situ high-temperature, high resolution transmission electron microscopy
      (HRTEM) was performed on an Al-Cu-Co decagonal quasicrystal, to investigate
      thermal fluctuation of phasons. A tiling pattern constructed from the HRTEM image
      was analyzed in the framework of the strip-projection method. Transitions between
      two local tile arrangements were observed at high temperature for the first time,
      and were shown to correspond to a thermal phason fluctuation.

PMID- 10970587
TI  - Scaling of crack surfaces and implications for fracture mechanics
AB  - The scaling laws describing the roughness development of crack surfaces are
      incorporated into the Griffith criterion. We show that, in the case of a Family
      Vicsek scaling, the energy balance leads to a purely elastic brittle behavior. On
      the contrary, it appears that an anomalous scaling reflects an R-curve behavior
      associated with a size effect of the critical resistance to crack growth in
      agreement with the fracture process of heterogeneous brittle materials exhibiting
      a microcracking damage.

PMID- 10970588
TI  - Does hard core interaction change absorbing-type critical phenomena?
AB  - It has been generally believed that hard core interaction is irrelevant to
      absorbing-type critical phenomena because the particle density is so low near an
      absorbing phase transition. We study the effect of hard core interaction on the N
      species branching annihilating random walks with two offspring and report that
      hard core interaction drastically changes the absorbing-type critical phenomena
      in a nontrivial way. Through a Langevin equation-type approach, we predict
      analytically the values of the scaling exponents, nu( perpendicular) = 2, z = 2,
      alpha = 1/2, and beta = 2 in one dimension for all N>1. Direct numerical
      simulations confirm our prediction. When the diffusion coefficients for different
      species are not identical, nu( perpendicular) and beta vary continuously with the
      ratios between the coefficients.

PMID- 10970589
TI  - Interface and contact line motion in a two phase fluid under shear flow
AB  - We use a coarse grained description to study the steady state interfacial
      configuration of a two phase fluid under steady shear. Dissipative relaxation of
      the order parameter leads to interfacial slip at the contact line, even with no
      slip boundary conditions on the fluid velocity. This relaxation occurs within a
      characteristic length scale l(0) = sqrt[xiD/V0], with xi the (microscopic)
      interfacial thickness, D an order parameter diffusivity, and V0 the boundary
      velocity. The steady state interfacial configuration is shown to satisfy a
      scaling form involving the ratio l(0)/L, where L is the width of the fluid layer,
      for a passive interface, and the capillary number as well for an active
      interface.

PMID- 10970590
TI  - Elastic modulus of polypyrrole nanotubes
AB  - The first measurements of the tensile elastic modulus of polypyrrole nanotubes
      are presented. The nanotubes were mechanically tested in three points bending
      using atomic force microscopy. The elastic tensile modulus was deduced from force
      curve measurements on different nanotubes with outer diameter ranging between 35
      and 160 nm. It is shown that the elastic modulus strongly increases when the
      thickness or outer diameter of polypyrrole nanotubes decreases.

PMID- 10970591
TI  - Nanometer-scale resolution of strain and interdiffusion in self-assembled
      InAs/GaAs quantum dots
AB  - Tomographic nanometer-scale images of self-assembled InAs/GaAs quantum dots have
      been obtained from surface-sensitive x-ray diffraction. Based on the three
      dimensional intensity mapping of selected regions in reciprocal space, the method
      yields the shape of the dots along with the lattice parameter distribution and
      the vertical interdiffusion profile on a subnanometer scale. The material
      composition is found to vary continuously from GaAs at the base of the dot to
      InAs at the top.

PMID- 10970592
TI  - Charge ordering in the TMTTF family of molecular conductors
AB  - Using one- and two-dimensional NMR spectroscopy applied to 13C spin-labeled
      (TMTTF)2AsF6 and (TMTTF)2PF6, we demonstrate the existence of an intermediate
      charge-ordered phase in the TMTTF family of charge-transfer salts. At ambient
      temperature, the spectra are characteristic of nuclei in equivalent molecules.
      Below a continuous charge-ordering transition temperature T(co), there is
      evidence for two inequivalent molecules with unequal electron densities. The
      absence of an associated magnetic anomaly indicates only the charge degrees of
      freedom are involved and the lack of evidence for a structural anomaly suggests
      that charge-lattice coupling is too weak to drive the transition.

PMID- 10970593
TI  - Electron correlation in C(4N+2) carbon rings: aromatic versus dimerized
      structures
AB  - The electronic structure of C(4N+2) carbon rings exhibits competing many-body
      effects of Huckel aromaticity, second-order Jahn-Teller (SOJT), and Peierls
      instability at large sizes. This leads to possible ground state structures with
      aromatic, bond angle, or bond length alternated geometry. Highly accurate quantum
      Monte Carlo results indicate the existence of a crossover between C10 and C14
      from bond angle to bond length alternation. The aromatic isomer is always a
      transition state. The gap opening mechanism is the SOJT effect, which coalesces
      with the Peierls regime as N-->infinity.

PMID- 10970595
TI  - Electronic properties of oxidized carbon nanotubes
AB  - The effect of oxygenation on the electronic properties of semiconducting carbon
      nanotubes is studied from first principles. The O2 is found to bind to a single
      walled nanotube with an adsorption energy of about 0.25 eV and to dope
      semiconducting nanotubes with hole carriers. Weak hybridization between carbon
      and oxygen is predicted for the valence-band edge states. The calculated density
      of states shows that weak coupling leads to conducting states near the band gap.
      The oxygen-induced gap closing for large-diameter semiconducting tubes is
      discussed as well. The influence of oxygen on the magnetic property is also
      addressed through a spin-polarized calculation and compared to experiment.

PMID- 10970594
TI  - First-principles study of Li-intercalated carbon nanotube ropes
AB  - We studied Li-intercalated carbon nanotube ropes by first-principles methods.
      Results show charge transfer between Li and C and small structural deformation
      due to intercalation. Both the interior of the nanotube and the interstitial
      space are susceptible for intercalation. The Li intercalation potential of a
      single-walled nanotube rope is comparable to that of graphite and almost
      independent of the Li density up to around LiC2, as observed in recent
      experiments. This density is significantly higher than that of Li-intercalated
      graphite, making the nanorope a promising candidate for the anode material in
      battery applications.

PMID- 10970596
TI  - Orbitally degenerate spin-1 model for insulating V2O3
AB  - Motivated by recent neutron, x-ray absorption, and resonant scattering
      experiments, we revisit the electronic structure of V2O3. We propose a model in
      which S = 1 V3+ ions are coupled in the vertical V-V pairs forming twofold
      orbitally degenerate configurations with S = 2. Ferro-orbital ordering of the V-V
      pairs gives a description which is consistent with all experiments in the
      antiferromagnetic insulating phase.

PMID- 10970597
TI  - Hot-electron effects in two-dimensional hopping with a large localization length
AB  - We have studied nonlinear effects in the resistance of a two-dimensional system
      with a large localization length on both sides of the crossover from weak to
      strong localization. It is shown that nonlinearity in the hopping regime is due
      to electron overheating rather than the field effects. This qualitatively new
      behavior is a signature of a two-dimensional hopping transport with a large
      localization length.

PMID- 10970598
TI  - Anomalous magnetic splitting of the kondo resonance
AB  - The splitting of the Kondo resonance in the density of states of an Anderson
      impurity in a finite magnetic field is calculated from the exact Bethe-ansatz
      solution. The result gives an estimate of the electron spectral function for a
      nonzero magnetic field and the Kondo temperature, with consequences for transport
      experiments on quantum dots in the Kondo regime. The strong correlations of the
      Kondo ground state cause a significant low-temperature reduction of the peak
      splitting. Explicit formulas are found for the shift and broadening of the Kondo
      peaks. A likely cause of the problems of large- N approaches to spin- 1 / 2
      impurities at finite magnetic field is suggested.

PMID- 10970599
TI  - Collective and independent-particle motion in two-electron artificial atoms
AB  - Investigations of the exactly solvable excitation spectra of two-electron quantum
      dots with a parabolic confinement, for different values of the parameter R(W)
      expressing the relative magnitudes of the interelectron repulsion and the zero
      point kinetic energy, reveal for large R(W) a rovibrational spectrum associated
      with a linear trimeric rigid molecule composed of the two electrons and the
      infinitely heavy confining dot. This spectrum transforms to that of a "floppy"
      molecule for smaller R(W). The conditional probability distribution calculated
      for the exact two-electron wave functions allows identification of the
      rovibrational excitations as rotations and stretching/bending vibrations.

PMID- 10970600
TI  - 2D-1D coupling in cleaved edge overgrowth
AB  - We study the scattering properties of an interface between a one-dimensional (1D)
      wire and a two-dimensional (2D) electron gas. Experiments were conducted in the
      highly controlled geometry provided by molecular bean epitaxy overgrowth onto the
      cleaved edge of a high quality GaAs /AlGaAs quantum well. Such structures allow
      for the creation of variable length 1D-2D coupling sections. We find ballistic 1D
      electron transport through these interaction regions with a mean free path as
      long as 6 &mgr;m. Our results explain the origin of the puzzling nonuniversal
      conductance quantization observed previously in such 1D wires.

PMID- 10970601
TI  - Spin-density and charge-density excitations in the paramagnetic phase of
      semiconductor double quantum well systems
AB  - The interplay of tunneling, Coulomb coupling, and many-body effects on the charge
      density excitation (CDE) and spin-density excitation (SDE) of double quantum well
      systems has been analyzed. For increasing interwell distances, the system moves
      from the strong-tunneling regime (one-well limit) towards the zero tunneling but
      still strongly Coulomb-coupled regime, passing by the intermediate regime of a
      small but finite tunneling-induced gap ( less, similar1 meV). Important
      renormalizations due to many-body effects are found in the long-wavelength limit
      of the CDE and SDE, with the former exhibiting a logarithmic correction to the
      single-particle linear dependence on the tunneling-induced gap, and the latter
      exhibiting a soft mode in the weak-tunneling, low-density regime. The oscillator
      strength of the SDE soft mode has been calculated and found to be clearly
      measurable.

PMID- 10970602
TI  - Local magnetic order vs superconductivity in a layered cuprate
AB  - We report on the phase diagram for charge-stripe order in La1.6-xNd0. 4SrxCuO4,
      determined by neutron and x-ray scattering studies and resistivity measurements.
      From an analysis of the in-plane resistivity motivated by recent nuclear
      quadrupole-resonance studies, we conclude that the transition temperature for
      local charge ordering decreases monotonically with x, and hence that local
      antiferromagnetic order is uniquely correlated with the anomalous depression of
      superconductivity at x approximately 1 / 8. This result is consistent with
      theories in which superconductivity depends on the existence of charge-stripe
      correlations.

PMID- 10970603
TI  - Charge order in NaV2O5 studied by EPR
AB  - We present angular dependent EPR measurements in NaV2O5 at X-band frequencies in
      the temperature range 4.2</=T</=670 K. A detailed analysis in terms of the
      antisymmetric Dzyaloshinski-Moriya and the anisotropic exchange interactions
      yields the following scheme of charge order: On decreasing temperature a quarter
      filled ladder with strong charge disproportions, existing for T>/=100 K, is
      followed by zigzag charge-order fluctuations which become long range and static
      below T(SP) = 34 K.

PMID- 10970604
TI  - Visualizing spin-dependent electronic collisions In ferromagnets
AB  - This work demonstrates experimentally and theoretically that the coincident two
      electron emission from a ferromagnetic surface, upon the impact of a polarized
      electron, carries detailed information on the spin-dependent electronic
      collisions in ferromagnets. The analysis of the calculated and the measured two
      electron spectra reveals the potential of the electron-pair emission technique
      for the study of (a) surface magnetism and (b) spin-dependent electron scattering
      dynamics in ferromagnets.

PMID- 10970605
TI  - Self-consistent density functional calculation of field emission currents from
      metals
AB  - We have developed a fully self-consistent method which is suitable to examine
      field emission currents, on the basis of the density functional theory. In our
      method, the nearby counterelectrode is not necessary. By using this method, we
      have investigated field emission currents from a biased metallic surface
      represented by the jellium model. We have found that the energy barrier between
      the jellium and vacuum becomes lower than the Fermi energy under strong electric
      fields (e.g., 10 V/nm for r(s) = 4 bohr). In this situation, the slope of the
      Fowler-Nordheim plot becomes flatter than that under a weaker field.

PMID- 10970606
TI  - Cloning of continuous quantum variables
AB  - The cloning of quantum variables with continuous spectra is analyzed. A Gaussian
      quantum cloning machine is exhibited that copies equally well the states of two
      conjugate variables such as position and momentum. It also duplicates all
      coherent states with a fidelity of 2/3. More generally, the copies are shown to
      obey a no-cloning Heisenberg-like uncertainty relation.

PMID- 10970607
TI  - Universal fault-tolerant quantum computation on decoherence-free subspaces
AB  - A general scheme to perform universal, fault-tolerant quantum computation within
      decoherence-free subspaces (DFSs) is presented. At most two-qubit interactions
      are required, and the system remains within the DFS throughout the entire
      implementation of a quantum gate. We show explicitly how to perform universal
      computation on clusters of the four-qubit DFS encoding one logical qubit each
      under spatially symmetric (collective) decoherence. Our results have immediate
      relevance to quantum computer implementations in which quantum logic is
      implemented through exchange interactions, such as the recently proposed spin
      spin coupled quantum dot arrays and donor-atom arrays.

PMID- 10970608
TI  - Quantum computing using dissipation to remain in a decoherence-free subspace
AB  - We propose a new approach to the implementation of quantum gates in which
      decoherence during the gate operations is strongly reduced. This is achieved by
      making use of an environment induced quantum Zeno effect that confines the
      dynamics effectively to a decoherence-free subspace.

PMID- 10970609
TI  - Spatiotemporal structure of traffic flow in a system with an open boundary
AB  - The spatiotemporal structure of a traffic flow pattern is investigated under the
      open boundary condition using the optimal velocity model. The parameter region
      where the uniform solution is convectively unstable is determined. It is found
      that a localized perturbation triggers a linearly unstable oscillatory solution
      out of the linearly unstable uniform state, and it is shown that the oscillatory
      solution is also convectively stabilized. It is demonstrated that the observed
      traffic pattern near an on-ramp can be interpreted as the noise sustained
      structure in the open flow system.

PMID- 10970610
TI  - Entropically driven colloidal crystallization on patterned surfaces
AB  - We investigate the self-assembly of colloidal spheres on periodically patterned
      templates. The surface potentials and the surface phases are induced entropically
      by the presence of dissolved, nonadsorbing polymers. A rich variety of two
      dimensional fluidlike and solidlike phases was observed to form on template
      potentials with both one- and two-dimensional symmetry. The same methodology was
      then used to nucleate an oriented single fcc crystal more than 30 layers thick.
      The general approach provides a new route for directed self-assembly of novel
      mesoscopic structures.

PMID- 10970611
TI  - One- and two-particle microrheology
AB  - We study the dynamics of rigid spheres embedded in viscoelastic media and address
      two questions of importance to microrheology. First, we calculate the complete
      response to an external force of a single bead in a homogeneous elastic network
      viscously coupled to an incompressible fluid. From this response function we find
      the frequency range where the standard assumptions of microrheology are valid.
      Second, we study fluctuations when embedded spheres perturb the media around them
      and show that mutual fluctuations of two separated spheres provide a more
      accurate determination of the complex shear modulus than do the fluctuations of a
      single sphere.

PMID- 10970612
TI  - Actively contracting bundles of polar filaments.
AB  - We introduce a phenomenological model to study the properties of bundles of polar
      filaments which interact via active elements. The stability of the homogeneous
      state, the attractors of the dynamics in the unstable regime, and the tensile
      stress generated in the bundle are discussed. We find that the interaction of
      parallel filaments can induce unstable behavior and is responsible for active
      contraction and tension in the bundle. The interaction between antiparallel
      filaments leads to filament sorting. Our model could apply to simple contractile
      structures in cells such as stress fibers.

PMID- 10970613
TI  - Feasible "Kochen-Specker" experiment with single particles
AB  - We present a simple experimental scheme which can be used to demonstrate an all
      or-nothing-type contradiction between noncontextual hidden variables and quantum
      mechanics. The scheme, which is inspired by recent ideas by Cabello and Garcia
      Alcaine, shows that even for a single particle, path and spin information cannot
      be predetermined in a noncontextual way.

PMID- 10970614
TI  - Supercriticality and transmission resonances in the dirac equation
AB  - It is shown that a Dirac particle of mass m and arbitrarily small momentum will
      tunnel without reflection through a potential barrier V = U(c)(x) of finite range
      provided that the potential well V = -U(c)(x) supports a bound state of energy E
      = -m. This is called a supercritical potential well.

PMID- 10970615
TI  - Bose-einstein condensation in trapped dipolar gases
AB  - We discuss Bose-Einstein condensation in a trapped gas of bosonic particles
      interacting dominantly via dipole-dipole forces. We find that in this case the
      mean-field interparticle interaction and, hence, the stability diagram are
      governed by the trapping geometry. Possible physical realizations include
      ultracold heteronuclear molecules, or atoms with laser induced electric dipole
      moments.

PMID- 10970616
TI  - Stable 85Rb bose-einstein condensates with widely tunable interactions
AB  - Bose-Einstein condensation has been achieved in a magnetically trapped sample of
      85Rb atoms. Long-lived condensates of up to 10(4) atoms have been produced by
      using a magnetic-field-induced Feshbach resonance to reverse the sign of the
      scattering length. This system provides new opportunities for the study of
      condensate physics. The variation of the scattering length near the resonance has
      been used to magnetically tune the condensate self-interaction energy over a wide
      range, extending from strong repulsive to large attractive interactions. When the
      interactions were switched from repulsive to attractive, the condensate shrank to
      below our resolution limit, and after approximately 5 ms emitted a burst of high
      energy atoms.

PMID- 10970617
TI  - Extraction of work from a single thermal bath in the quantum regime
AB  - The stationary state of a quantum particle strongly coupled to a quantum thermal
      bath is known to be non-Gibbsian, due to entanglement with the bath. For harmonic
      potentials, where the system can be described by effective temperatures,
      thermodynamic relations are shown to take a generalized Gibbsian form that may
      violate the Clausius inequality. For the weakly anharmonic case, a Fokker-Planck
      type description is constructed. It is shown that then work can be extracted from
      the bath by cyclic variation of a parameter. These apparent violations of the
      second law are the consequence of quantum coherence in the presence of the
      slightly off-equilibrium nature of the bath.

PMID- 10970619
TI  - Extracting weak phase information from B-->V1V2 decays
AB  - We describe a new method for extracting weak, CP-violating &Dmacr;phase
      information, with no hadronic uncertainties, from an angular analysis of B-->V1V2
      decays, where V1 and V2 are vector mesons. The quantity sin (2)(2beta+gamma) can
      be cleanly obtained from the study of decays such as B(0)(d)(t)-->D*+/-rho(-/+),
      D(*+/-)a(-/+)(1), D(;) *0K(;) (*0), etc. Similarly, one can use B(0)(s)(t)-
      >D(*+/-)(s)K*-/+ to extract sin (2)gamma. There are no penguin contributions to
      these decays. It is possible that sin (2)(2beta+gamma) will be the second
      function of CP phases, after sin2beta, to be measured at B factories.

PMID- 10970620
TI  - Casimir scaling as a test of QCD vacuum models
AB  - Recent accurate lattice measurements of static potentials between sources in
      various representations of the gauge group SU(3) performed by Bali, provide a
      crucial test of different QCD vacuum models. The Casimir scaling of the potential
      observed for all measured distances can be explained as being due to strong
      suppression of higher cumulants contribution.

PMID- 10970618
TI  - Universality class of absorbing phase transitions with a conserved field
AB  - We investigate the critical behavior of systems exhibiting a continuous absorbing
      phase transition in the presence of a conserved field coupled to the order
      parameter. The results obtained point out the existence of a new universality
      class of nonequilibrium phase transitions that characterizes a vast set of
      systems including conserved threshold transfer processes and stochastic sandpile
      models.

PMID- 10970621
TI  - KARMEN time anomaly: search for a neutral particle of mass 33.9 MeV in pion decay
AB  - We have searched for the pion decay pi(+)-->&mgr;+X, where X is a neutral
      particle of mass 33.905 MeV. This process was suggested by the KARMEN
      Collaboration to explain an anomaly in their observed time distribution of
      neutrino induced reactions. Having measured the muon momentum spectrum of charged
      pions decaying in flight, we find no evidence for this process and place an upper
      limit on the branching fraction eta</=6.0x10(-10) of such a decay at a 95%
      confidence level.

PMID- 10970622
TI  - Excitation functions of the analyzing power in pp--> scattering from 0.45 to 2.5
      GeV
AB  - Excitation functions A(N)(p(p),Theta(c.m.)) of the analyzing power in pp-->
      elastic scattering have been measured with a polarized atomic hydrogen target for
      projectile momenta p(p) between 1000 and 3300 MeV/ c. The experiment was
      performed for scattering angles 30 degrees </=Theta(c.m.)</=90 degrees using the
      recirculating beam of the proton storage ring COSY during acceleration. The
      resulting excitation functions and angular distributions of high internal
      consistency have significant impact on the recent phase shift solution SAID SP99,
      in particular, on the spin triplet phase shifts between 1000 and 1800 MeV, and
      demonstrate the limited predictive power of single-energy phase shift solutions
      at these energies.

PMID- 10970623
TI  - Barrier-wave-internal-wave interference and airy minima in 16O16+O elastic
      scattering
AB  - Taking 16O+16O elastic scattering at 124 MeV as an example, we show that a
      barrier-wave-internal-wave decomposition of the elastic scattering amplitude
      provides valuable information on the light heavy-ion interaction and complements
      the more conventional nearside-farside decomposition. In particular, we show that
      the Airy minima present in the angular distributions are due to a barrier-wave
      internal-wave interference mechanism, which sheds additional light on the
      exceptional transparency displayed by some light heavy-ion scattering systems.
      Extension of these ideas to other fields, like atomic and molecular collision
      physics, could prove rewarding.

PMID- 10970624
TI  - Electromagnetic cross sections of double giant dipole resonances in 136Xe and
      208Pb within the phonon damping model
AB  - The electromagnetic cross sections of the double giant dipole resonances (DGDR)
      in 136Xe and 208Pb are calculated using the strength functions obtained within
      the phonon damping model. The parameters of the model have been selected to
      describe reasonably well the single giant dipole resonance in these nuclei. The
      results are found in an overall agreement with the recent experimental data for
      the DGDR cross sections in exclusive measurements at near-relativistic energies.

PMID- 10970625
TI  - Observation of nuclear excitation by electron transition in 197Au with
      synchrotron X rays and an avalanche photodiode
AB  - We have succeeded in observing nuclear excitation by electron transition (NEET)
      in 197Au by a new method. Monochromatic x-rays of synchrotron radiation were used
      to ionize the K shell of gold atoms in a target foil. The internal-conversion
      electrons emitted from excited nuclei were detected with a silicon avalanche
      photodiode. At a photon energy of 80.989 keV, the NEET probability in 197Au was
      determined to be (5.0+/-0.6)x10(-8) from a comparison of the event number per
      photon between NEET and the nuclear resonance at 77.351 keV.

PMID- 10970626
TI  - Breakdown of stabilization of atoms interacting with intense, high-frequency
      laser pulses
AB  - An analysis of the influence of the magnetic field of an intense, high-frequency
      laser pulse on the stabilization of an atomic system is presented. We demonstrate
      that at relatively modest intensities the magnetic field can significantly alter
      the dynamics of the system. In particular, a breakdown of stabilization occurs,
      thereby restricting the intensity regime in which the atom is relatively stable
      against ionization. Counterpropagating pulses do not negate the detrimental
      effects of the magnetic field. We compare our quantum mechanical results with
      classical Monte Carlo simulations.

PMID- 10970627
TI  - Instabilities in a magneto-optical trap: noise-induced dynamics in an atomic
      system
AB  - The instabilities observed in the atomic cloud of a magneto-optical trap are
      experimentally studied through the dynamics of the center of mass location and
      the cloud population. Two dynamical components are identified: a slow, stochastic
      one affects both variables, and a fast, deterministic one affects only the center
      of mass location. A one-dimensional stochastic model taking into account the
      shadow effect is developed from these observations and reproduces the
      experimental behavior. It is shown that instabilities are driven by noise and
      present stochastic resonancelike characteristics.

PMID- 10970628
TI  - Phase control of photoabsorption in optically dense media
AB  - We present a self-consistent theory, as well as an illustrative application to a
      realistic system, of phase control of photoabsorption in an optically dense
      medium. We demonstrate that, when propagation effects are taken into
      consideration, the impact on phase control is significant. Independent of the
      value of the initial phase difference between the two fields, over a short scaled
      distance of propagation, the medium tends to settle the relative phase so that it
      cancels the atomic excitation. In addition, we find some rather unusual behavior
      for an optically thin layer.

PMID- 10970629
TI  - Observation of ionization in a crystal interferometer
AB  - We present a new interferometric setup where interference of a fast probe
      electron affects the ionization cross section of an atom. Interference is
      detected in the intensity of the inelastically scattered electrons at the Bragg
      scattering angle in transmission. The crystal serves both as a target for core
      ionization and as a beam-splitting and phase-shifting device.

PMID- 10970630
TI  - Effects of local fields on spontaneous emission in dielectric media
AB  - The local-field renormalization of the spontaneous emission rate in a dielectric
      is explicitly obtained from a fully microscopic quantum-electrodynamical, many
      body derivation of Langevin-Bloch operator equations for two-level atoms embedded
      in an absorptive and dispersive, linear dielectric host. We find that the
      dielectric local-field enhancement of the spontaneous emission rate is smaller
      than indicated by previous studies.

PMID- 10970631
TI  - Giant violations of classical inequalities through conditional homodyne detection
      of the quadrature amplitudes of light
AB  - Conditional homodyne detection is proposed as an extension of the intensity
      correlation technique introduced by Hanbury-Brown and Twiss [Nature (London) 177,
      27 (1956)]. It detects giant quadrature amplitude fluctuations for weakly
      squeezed light, violating a classical bound by orders of magnitude. Fluctuations
      of both quadrature amplitudes are anomalously large. The squeezed quadrature also
      exhibits an anomalous phase.

PMID- 10970632
TI  - New mechanisms for lack of equipartition of energy
AB  - We describe several mechanisms that prevent equipartition of energy in mechanical
      systems. In certain regimes, we present a quantitative prediction of the relative
      abundance of orbits exhibiting these mechanisms. This quantitative prediction is
      confirmed in numerical experiments.

PMID- 10970633
TI  - Diffraction management
AB  - By using the diffraction properties of waveguide arrays, we propose a scheme to
      produce structures with designed diffraction. We fabricated arrays with reduced,
      canceled, and even reversed diffraction. Results of experiments with such
      waveguides are presented and compared with the predictions made by coupled-mode
      theory.

PMID- 10970634
TI  - Critical enhancement of photorefractive beam coupling
AB  - We show that a hybridization of the optical and material nonlinearities takes
      place near the threshold of the subharmonic generation in photorefractive
      crystals. It results in a critical (with a singularity) enhancement of the rate
      of spatial amplification of light waves and leads to a variety of new optical
      critical phenomena.

PMID- 10970635
TI  - Transverse instability of optical spatiotemporal solitons in quadratic media.
AB  - We present experimental and numerical observations of transverse instability in
      quadratic media under conditions that emphasize the inherently spatiotemporal and
      multidimensional nature of the wave propagation. Intensity-dependent beam
      filamentation is shown to be closely connected to the periodic evolution of
      quadratic solitons, and implications for the generation of three-dimensional
      spatiotemporal solitons are discussed.

PMID- 10970636
TI  - Tunable photonic crystals with semiconducting constituents
AB  - We propose that the photonic band structure (PBS) of semiconductor-based photonic
      crystals (PCs) can be made tunable if the free-carrier density is sufficiently
      high. In this case, the dielectric constant of the semiconductor, modeled as
      varepsilon(omega) = varepsilon(0)(1-omega(2)(p)/omega(2)), depends on the
      temperature T and on the impurity concentration N through the plasma frequency
      omega(p). Then the PBS is strongly T and N dependent; it is even possible to
      obliterate a photonic band gap. This is shown by calculating the 2D PBS for PCs
      that incorporate either intrinsic InSb or extrinsic Ge.

PMID- 10970637
TI  - Observation of inhomogeneous spectral broadening of stimulated brillouin
      scattering in an optical fiber
AB  - We report experimental results which show that the stimulated Brillouin
      scattering (SBS) spectrum in an optical fiber is inhomogeneous, exhibiting
      spectral broadening and hole burning under cw monochromatic laser excitation.
      This phenomenon arises from the waveguide interaction of the pump and Stokes
      signals and is a fundamental property of SBS in waveguiding systems due to their
      ability to confine a fan of radiation wave vector directions.

PMID- 10970638
TI  - Inward transport and compression of a positron plasma by a rotating electric
      field
AB  - Inward transport of a magnetized pure positron plasma confined in a Penning
      Malmberg trap is produced by applying a rotating electric field to the plasma.
      Compression is observed over a broad range of frequencies. Compression factors up
      to 20 in central density were obtained. Positron collisions with a neutral buffer
      gas are used to counteract the heating due to the rotating electric field. The
      results have implications for a variety of applications including the production
      of brightness enhanced positron beams, the study of electron-positron plasmas,
      and antihydrogen production.

PMID- 10970639
TI  - Compressibility and polygonization of single-walled carbon nanotubes under
      hydrostatic pressure
AB  - Single-walled carbon nanotubes show linear elasticity under hydrostatic pressure
      up to 1.5 GPa at room temperature. The volume compressibility, measured by in
      situ synchrotron x-ray diffraction, has been determined to be 0.024 GPa (-1).
      Theoretical calculations suggest that single-walled carbon nanotubes are
      polygonized when they form bundles of hexagonal close-packed structure and the
      intertubular gap is smaller than the equilibrium spacing of graphite (002) (d =
      3.35 A). It has also been determined that the deformation of the trigonal
      nanotube lattice under hydrostatic pressure is reversible up to 4 GPa, beyond
      which the nanotube lattice is destroyed.

PMID- 10970640
TI  - Path integral monte carlo calculation of the deuterium hugoniot
AB  - Restricted path integral Monte Carlo simulations have been used to calculate the
      equilibrium properties of deuterium for two densities: 0.674 and 0.838 g cm(-3) (
      r(s) = 2.00 and 1.86) in the temperature range of 10(5)</=T</=10(6) K. We
      carefully assess size effects and dependence on the time step of the path
      integral. Further, we compare the results obtained with a free particle nodal
      restriction with those from a self-consistent variational principle, which
      includes interactions and bound states. By using the calculated internal energies
      and pressures, we determine the shock Hugoniot and compare with recent laser
      shock wave experiments as well as other theories.

PMID- 10970641
TI  - Melting process and interface instability of highly magnetized solid 3He: role of
      the magnetization gradient
AB  - We elucidate the melting process of highly magnetized solid 3He by observing the
      magnetization profile and the liquid-solid interface simultaneously. Clear
      enhancements of magnetization and magnetization gradients at the interface of
      both the solid and the liquid were observed during melting. These measurements
      provide a mesoscopic confirmation of the melting scenario of Castaing and
      Nozieres, and explain the long delay before the instability sets in: The
      magnetization gradient in the liquid leads to an initial suppression of the
      melting instability, in accordance with our extension of the stability analysis
      of Puech et al. This resolves the discrepancy between theory and experiment.

PMID- 10970642
TI  - Nature of metal-ceramic adhesion: computational experiments with Co on TiC
AB  - By means of first-principles computational experiments, the microscopic mechanism
      of metal-carbide adhesion is revealed. Density-functional-theory results for the
      Co /TiC(001) interface show the interface bonding to be dominated by Co-C bonds.
      The effective number of bonds is controlled by an interplay between lattice
      mismatch and relaxation effects. The particular strength of the Co-C bond is
      explained in terms of interface-induced features of the electronic states, in
      particular, a novel metal-modified covalent bond. The calculated adhesion
      strength agrees well with results of wetting experiments.

PMID- 10970643
TI  - Spontaneous formation of indium-rich nanostructures on InGaN(0001) surfaces
AB  - InGaN(0001) surfaces prepared by molecular beam epitaxy have been studied using
      scanning tunneling microscopy and first-principles total energy calculations.
      Nanometer-size surface structures are observed consisting of either vacancy
      islands or ordered vacancy rows. The spontaneous formation of these structures is
      shown to be driven by significant strain in the surface layers and by the
      relative weakness of the In-N bond compared to Ga-N. Theory indicates that In
      will preferentially bind at the edges and interior of the structures, thereby
      giving rise to an inhomogeneous In distribution at the surface.

PMID- 10970644
TI  - Five wave mixing: surface-specific transient grating spectroscopy as a probe of
      low frequency intermolecular adsorbate motion
AB  - Surface-specific five wave mixing spectroscopy is used to examine adsorbate
      dynamics at the fused silica/air interface. Signals whose temporal response is
      significantly broader than the instantaneous fourth-order electronic
      polarizability are attributed to low frequency, adsorbate nuclear motion. Based
      on the dependence of these dynamics on the moment of inertia and their comparison
      with dynamics observed in liquids, the five wave mixing temporal response has
      been assigned to adsorbate intermolecular librational motion. Demonstration of
      this new fourth-order technique allows one, in principle, to extend all third
      order nonlinear bulk-phase spectroscopies to surfaces and interfaces with
      specificity.

PMID- 10970645
TI  - Nature, strength, and consequences of indirect adsorbate interactions on metals
AB  - Atoms and molecules adsorbed on metals affect each other indirectly even over
      considerable distances. Via systematic density-functional calculations, we
      establish the nature and strength of such interactions, and explain for what
      adsorbate systems they critically affect important materials properties. This is
      verified in kinetic Monte Carlo simulations of epitaxial growth, which help
      rationalize a number of recent experimental reports on anomalously low diffusion
      prefactors.

PMID- 10970646
TI  - Electronic resonance and symmetry in single-molecule inelastic electron tunneling
AB  - Inelastic electron tunneling spectroscopy and microscopy with a scanning
      tunneling microscope revealed two vibrational modes showing a decrease in
      conductance at +/-82.0 and +/-38.3 mV sample bias for single oxygen molecules
      chemisorbed on the fourfold hollow sites of Ag(110) surface at 13 K. The spatial
      distribution of the vibrational intensities exhibited pi(g)-orbital
      (perpendicular to surface) symmetry of O2 with the molecular axis along the [001]
      direction. These results are attributed to resonant inelastic electron tunneling.

PMID- 10970647
TI  - Vibrationally mediated negative differential resistance in a single molecule
AB  - A new mechanism for negative differential resistance (NDR) has been discovered
      and involves a single molecule in the junction of a scanning tunneling
      microscope. The NDR was observed at voltages corresponding to the vibrational
      energies of single pyrrolidine molecules on the (001) surface of copper at 9 K.
      This vibrationally mediated NDR contrasts with the previously known mechanisms
      which all involve the electronic states of the conducting media.

PMID- 10970648
TI  - Equilibrium shape of two-dimensional islands under stress
AB  - We show that the equilibrium shape anisotropy of two-dimensional islands in
      heteroepitaxial growth depends on island size, a consequence of the presence of
      strain. Even in homoepitaxy, in which the island shape has conventionally been
      equated with the ratio of step energies, a substrate surface stress anisotropy
      can influence island shape.

PMID- 10970649
TI  - Temperature-dependent interfacial stiffness of the disorder layer in a thin Cu3Au
      alloy film
AB  - The order-disorder transition in a 170 A thick Cu3Au(111) epitaxial alloy film is
      examined using x-ray diffraction techniques. Below the transition temperature T0,
      a disordered surface layer of thickness l is detected. This layer exhibits
      wetting behavior, i.e., l increases, obeying a logarithmic growth law on approach
      to T0. We show by a detailed analysis of the order parameter profiles that the
      stiffness of the order-disorder interface is temperature dependent, resulting in
      a nonuniversality of the wetting transition.

PMID- 10970650
TI  - Three-phase contact line energetics from nanoscale liquid surface topographies
AB  - The contact line tension of a three-phase system (solid-liquid-vapor) is
      determined from the liquid surface topography data obtained with scanning force
      microscopy. The data are analyzed in two completely complementary ways, one of
      which is based on the modified Young equation, the other on the effective
      interface potential derived from the profile of the liquid-vapor interface in the
      three-phase region. The two methods agree quite well for the systems
      investigated. Contact line tensions are in the range of 10(-11) to 10(-10) J/m,
      which is consistent with theory.

PMID- 10970651
TI  - Density functional for a model colloid-polymer mixture
AB  - We present a density functional theory for mixtures of (hard sphere) colloidal
      particles and ideal polymers. For this extreme nonadditive system we employ a
      fundamental measures approach to construct a functional which incorporates the
      correct dimensional crossover and the exact low density limit. In bulk fluid
      mixtures the functional yields the same free energy and, therefore, the same gas
      liquid (demixing) transition as given by free-volume theory. It generates
      consistent pair correlation functions; the partial structure factors S(ij)(k)
      diverge, as k-->0, at the critical point obtained from the free energy. Our
      results for the structure agree well with those from simulation and Percus-Yevick
      theory.

PMID- 10970652
TI  - Pressure induced quantum critical point and non-fermi-liquid behavior in BaVS3
AB  - The phase diagram of BaVS3 is studied under pressure using resistivity
      measurements. The temperature of the metal to nonmagnetic Mott insulator
      transition decreases under pressure, and vanishes at the quantum critical point
      p(cr) = 20 kbar. We find two kinds of anomalous conducting states. The high
      pressure metallic phase is a non-Fermi liquid described by Deltarho approximately
      T(n) where n = 1.2-1.3 at 1<T<40 K. At p<p(cr), the transition is preceded by a
      wide precursor region with critically increasing resistivity which we ascribe to
      the opening of a soft Coulomb gap.

PMID- 10970653
TI  - Missing 2k(F) response for composite fermions in phonon drag
AB  - The response of composite fermions to large wave vector scattering has been
      studied through phonon drag measurements. While the response retains qualitative
      features of the electron system at zero magnetic field, notable discrepancies
      develop as the system is varied from a half-filled Landau level by changing
      density or field. These deviations, which appear to be inconsistent with the
      current picture of composite fermions, are absent if half filling is maintained
      while changing density. There remains, however, a clear deviation from the
      temperature dependence anticipated for 2k(F) scattering.

PMID- 10970654
TI  - Out-of-equilibrium kondo effect in double quantum dots
AB  - The out-of-equilibrium transport properties of a double quantum dot system in the
      Kondo regime are studied theoretically by means of a two-impurity Anderson
      Hamiltonian with interimpurity hopping. The Hamiltonian is solved by means of a
      nonequilibrium generalization of the slave-boson mean-field theory. It is
      demonstrated that measurements of the differential conductance dI/dV, for
      appropriate values of voltages and tunneling couplings, can give a direct
      observation of the coherent superposition between the many-body Kondo states of
      each dot. For large voltages and arbitrarily large interdot tunneling, there is a
      critical voltage above which the physical behavior of the system again resembles
      that of two decoupled quantum dots.

PMID- 10970655
TI  - Evidence of a reentrant peierls distortion in liquid GeTe
AB  - The local atomic order of semiconducting liquid GeTe is studied using first
      principles molecular-dynamics simulations. Our work points out a high degree of
      alternating chemical order in the liquid and demonstrates the presence of a
      Peierls distortion close above the melting temperature. This distortion, absent
      in the high temperature crystalline structure of NaCl type, is a remnant of the
      atomic arrangement in the A7 low temperature crystalline phase. It disappears
      slowly with temperature, as the liquid evolves from a semiconducting to a
      metallic state.

PMID- 10970656
TI  - Hall crystal states at nu = 2 and moderate landau level mixing
AB  - The nu = 2 quantum Hall state at low Zeeman coupling is well known to be a
      translationally invariant singlet if Landau level mixing is small. At zero Zeeman
      interaction, as Landau level mixing increases, the translationally invariant
      state becomes unstable to an inhomogeneous state. This is the first realistic
      example of a full Hall crystal, which shows the coexistence of quantum Hall order
      and density wave order. The full Hall crystal differs from the more familiar
      Wigner crystal by a topological property, which results in it having only
      linearly dispersing collective modes at small q, and no q(3/2) magnetophonon. I
      present calculations of the topological number and the collective modes.

PMID- 10970657
TI  - Metal-semiconductor nanocontacts: silicon nanowires
AB  - Silicon nanowires assembled from clusters or etched from the bulk, connected to
      aluminum electrodes and passivated, are studied with large-scale local-density
      functional simulations. Short ( approximately 0.6 nm) wires are fully metallized
      by metal-induced gap states resulting in finite conductance ( approximately
      e(2)/h). For longer wires ( approximately 2.5 nm) nanoscale Schottky barriers
      develop with heights larger than the corresponding bulk value by 40% to 90%.
      Electric transport requires doping dependent gate voltages with the conductance
      spectra exhibiting interference resonances due to scattering of ballistic
      channels by the contacts.

PMID- 10970658
TI  - Quantum dot as spin filter and spin memory
AB  - We consider a quantum dot in the Coulomb blockade regime weakly coupled to
      current leads and show that in the presence of a magnetic field it acts as an
      efficient spin filter (at the single-spin level), producing a spin-polarized
      current. Conversely, if the leads are fully spin polarized the up or the down
      state of the spin on the dot results in a large sequential or a small cotunneling
      current, and, thus, together with ESR techniques, the setup can be operated as a
      single-spin memory.

PMID- 10970659
TI  - Photoemission spectroscopy of the strong-coupling superconducting transitions in
      lead and niobium
AB  - We study the changes in the electronic structure associated with low- T(c) strong
      coupling superconducting transitions in Pb and Nb using ultrahigh-resolution (2.3
      meV) temperature-dependent (5.3-12.0 K) photoemission spectroscopy. We observe
      peaks in the density of states on entering the superconducting-phase accompanying
      gap formation and spectacular redistribution of spectral weight at low energy
      scales as a function of temperature. The well-known peak-dip feature of the high-
      T(c) cuprates is seen in Pb, making it a characteristic of strong-coupling
      superconductivity.

PMID- 10970660
TI  - BCS-like density of states in superconducting A3C60 surfaces
AB  - We report on an ultrahigh resolution photoemission study on the topmost molecular
      layer of K3C60 and Rb3C60 films below and above the superconducting transition
      temperature T(C). We observed not only clear evidence for the opening of the
      superconducting gap, but also a modification in the photoemission line shape
      consistent with a change from a normal-metallic to a BCS-like density of states,
      including the formation of a condensation peak. The data can be accurately
      modeled by a BCS-type function with a gap Delta derived from T(C) in the weak
      coupling limit ( 2Delta/k(B)T(C) = 3.53).

PMID- 10970661
TI  - Superconductor-insulator transition in a two-dimensional array of resistively
      shunted small josephson junctions
AB  - We have fabricated two-dimensional (2D) small-Josephson-junction arrays of which
      each Al-AlOx-Al junction is shunted by a Cr resistor. The arrays with large
      junction resistance and large charging energy show a transition from insulating
      to superconducting behavior when the shunt resistance is lowered below a critical
      value, which is close to 2R(Q) ( R(Q) identical withh/4e(2) = 6.45 kOmega). The
      measured phase diagram is consistent with theories of quantum-fluctuation-driven
      and dissipation-driven phase transitions in the 2D Josephson-junction array with
      Ohmic shunt resistors.

PMID- 10970662
TI  - Local magnetism of isolated Mo atoms at substitutional and interstitial sites in
      Yb metal: experiment and theory
AB  - We have observed large 4d moments on isolated Mo atoms at substitutional and
      octahedral interstitial lattice sites in Yb metal, showing Curie-Weiss local
      susceptibility and a Korringa-like spin relaxation rate. The interstitial Mo
      atoms, despite strong hybridization with the Yb neighbors, show rather small
      Kondo temperature ( T(K)</=60 K), implying high moment stability. While magnetism
      of Mo at the substitutional site is consistent with Kondo-type d-sp interaction,
      we suggest that moment stability at the interstitial site is strongly influenced
      by ferromagnetic polarization of Yb-4f5d band electrons.

PMID- 10970663
TI  - Crossover from dilute to majority spin freezing in two leg ladder system
      Sr(Cu,Zn)2O3
AB  - Muon spin relaxation has been measured in Sr(Cu1-xZnx)2O3. The results for low Zn
      concentration x</=0.6% are consistent with freezing of dilute moments, with one
      Cu spin for each Zn, having approximately 0.5&mgr;(B) frozen moment. A sharp
      increase of the relaxation rate at T-->0 occurred with increasing x around x
      approximately 0.8%, accompanied by a change of line shape to that expected in a
      concentrated magnetic environment. Analyses of the results for x>/=0.8% suggest
      that the majority of Cu moments participate in spin freezing, yet with a
      significantly reduced and spatially inhomogeneous moment size having a 1D
      correlation length xi approximately 6 lattice units, or a 2D correlation area
      involving approximately 19 Cu spins.

PMID- 10970664
TI  - Ultrafast spin dynamics and critical behavior in half-metallic ferromagnet:
      Sr2FeMoO6
AB  - Ultrafast spin dynamics in ferromagnetic half-metallic compound Sr2FeMoO6 is
      investigated by pump-probe measurements of the magneto-optical Kerr effect. The
      half-metallic nature of this material gives rise to anomalous thermal insulation
      between spins and electrons and allows us to pursue the spin dynamics from a few
      to several hundred picoseconds after the optical excitation. The optically
      detected magnetization dynamics clearly shows the crossover from microscopic
      photoinduced demagnetization to macroscopic critical behavior with universal
      power law divergence of relaxation time for a wide dynamical critical region.

PMID- 10970665
TI  - Magnetic correlations in nanostructured ferromagnets
AB  - Small-angle neutron scattering experiments on nanostructured Fe, Co, and Ni
      reveal grain-size dependent magnetic correlations across grain boundaries. In Fe,
      a minimum of the correlation length is observed for grain sizes of the order of
      the bulk domain-wall width where the coercive field has a maximum. The results
      are explained within a generalization of the random-anisotropy model that takes
      into account domain-wall formation within grains and reduced interface coupling.

PMID- 10970666
TI  - Photoinduced magnetism, dynamics, and cluster glass behavior of a molecule-based
      magnet
AB  - The dynamic susceptibility study of photoinduced magnetism in a molecule-based
      magnet, K1-2xCo1+x[Fe(CN)(6)];yH(2)O (0.2</=x</=0.4,y approximately 5), is
      reported. Upon excitation with visible light the material has substantial changes
      in linear and nonlinear ac susceptibility and dc magnetization. The results
      demonstrate cooperative freezing of magnetic moments and absence of true long
      range magnetic order. The ground and photoexcited states are described within a
      cluster glass model, with photoinduced increase in spin concentration leading to
      a shift of the dynamics to longer length and time scales and higher temperatures.

PMID- 10970667
TI  - Mesoscopic microwave dispersion in ferroelectric thin films
AB  - The microwave dielectric response of a ferroelectric thin film is measured
      locally using time-resolved confocal scanning optical microscopy. Measurements
      performed on an ensemble of nanometer-scale regions show a well-defined phase
      shift between the paraelectric and ferroelectric response at 2-4 GHz. Application
      of a static electric field produces large local variations in the phase of the
      ferroelectric response. These variations are attributed to the growth of in-plane
      ferroelectric nanodomains whose size-dependent relaxation frequencies lead to
      strong dielectric dispersion at mesoscopic scales.

PMID- 10970668
TI  - Demonstration of sixth-order coulomb correlations in a semiconductor single
      quantum well
AB  - Six-wave mixing in a ZnSe quantum well is investigated and compared with
      microscopic theory. We demonstrate that sixth-order Coulomb correlations have a
      significant qualitative impact on the nonlinear optical response. Six-wave mixing
      is shown to be a uniquely sensitive tool for investigation of correlations beyond
      the four-point level.

PMID- 10970669
TI  - Quantum algorithm for distributed clock synchronization
AB  - The clock synchronization problem is to determine the time difference Delta
      between two spatially separated clocks. When message delivery times between the
      two clocks are uncertain, O(2(2n)) classical messages must be exchanged between
      the clocks to determine n digits of Delta. On the other hand, as we show, there
      exists a quantum algorithm to obtain n digits of Delta while communicating only
      O(n) quantum messages.

PMID- 10970670
TI  - Quantum clock synchronization based on shared prior entanglement
AB  - We demonstrate that two spatially separated parties (Alice and Bob) can utilize
      shared prior quantum entanglement, and classical communications, to establish a
      synchronized pair of atomic clocks. In contrast to classical synchronization
      schemes, the accuracy of our protocol is independent of Alice's or Bob's
      knowledge of their relative locations or of the properties of the intervening
      medium.

PMID- 10970671
TI  - Sophisticated quantum search without entanglement
AB  - Grover's quantum search algorithm has recently been implemented without
      entanglement, by replacing multiple particles with a single particle having
      exponentially many states. We recall that all physical resources must be
      accounted for to quantify algorithm complexity, and that this scheme typically
      incurs exponential costs in some other resource(s). In particular, we demonstrate
      that a recent experimental realization requires exponentially increasing
      precision. There is, however, a quantum algorithm which searches a
      "sophisticated" database (not unlike a Web search engine) with a single query,
      but which we show does not require entanglement even for multiparticle
      implementations.

PMID- 10970672
TI  - Relating the microscopic and macroscopic response of a polymeric fluid in a
      shearing flow.
AB  - The microscopic and macroscopic response of a polymer solution in start-up shear
      flow was investigated using fluorescence microscopy of single molecules, bulk
      viscosity measurements, and Brownian dynamics simulations. An overshoot in
      viscosity was observed upon flow inception and understood via the observed
      molecular extension and by simulation findings. Increasing the polymer
      concentration up to six times the overlap concentration ( C(*)) has no effect on
      the character of the dynamics of individual molecules.

PMID- 10970673
TI  - Model of convergent extension in animal morphogenesis.
AB  - We argue that energy minimization can explain the pattern of cell movements in
      the morphogenetic process known as convergent extension provided that the cell
      cell adhesive energy has a certain type of anisotropy, which we describe. This
      single simple property suffices to cause the cell elongation, cell alignment, and
      lengthening of a cellular array that characterize convergent extension. We show
      that the final aspect ratio of the array of cells depends on the anisotropy and
      is independent of the initial configuration and of the degree of cell elongation.

PMID- 10970675
TI  - Turbulence and wave breaking effects on air-water gas exchange
AB  - We present an experimental characterization of the effects of turbulence and
      breaking gravity waves on air-water gas exchange in standing waves. We identify
      two regimes that govern aeration rates: turbulent transport when no wave breaking
      occurs and bubble dominated transport when wave breaking occurs. In both regimes,
      we correlate the qualitative changes in the aeration rate with corresponding
      changes in the wave dynamics. In the latter regime, the strongly enhanced
      aeration rate is correlated with measured acoustic emissions, indicating that
      bubble creation and dynamics dominate air-water exchange.

PMID- 10970674
TI  - Time delay effect in a living coupled oscillator system with the plasmodium of
      Physarum polycephalum.
AB  - A living coupled oscillator system was constructed by a cell patterning method
      with a plasmodial slime mold, in which parameters such as coupling strength and
      distance between the oscillators can be systematically controlled. Rich
      oscillation phenomena between the two-coupled oscillators, namely,
      desynchronizing and antiphase/in-phase synchronization were observed according to
      these parameters. Both experimental and theoretical approaches showed that these
      phenomena are closely related to the time delay effect in interactions between
      the oscillators.

PMID- 10970676
TI  - The role of cyclooxygenases in endotoxin- and interleukin-1-induced hypophagia.
AB  - Endotoxin (lipopolysaccharide, LPS) and interleukin-1 (IL-1) reduce food intake
      in rodents. Cyclooxygenase (COX) inhibitors have long been known to attenuate
      these responses, but recent work has revealed the existence of two distinct
      isoforms of the enzyme, COX1 and COX2, with different characteristics and
      functions. Therefore, we reassessed the COX involvement using inhibitors with
      different selectivities for COX1 and COX2. Feeding was assessed in nondeprived
      mice by measuring the intake of sweetened milk in a 30-minute period, as well as
      daily food pellet intake. LPS and IL-1beta consistently reduced milk intake.
      Treatment of the mice with the selective COX1 inhibitor, piroxicam, attenuated
      the hypophagic responses to IL-1 and LPS. Similar results were obtained with
      diclofenac. The hypophagic responses to LPS and IL-1beta were not affected by the
      COX2-selective inhibitors nimesulide and NS-398 at doses considered selective for
      COX2, but were inhibited by higher doses. Pretreatment of the mice with aspirin,
      an irreversible inhibitor of COX1 and COX2, prevented the hypophagic response to
      IL-1, 16 h, but not 40 h later. Taken together, these results suggest that COX1
      may be the major isozyme involved in the hypophagic responses to LPS and IL-1,
      but a role for COX2 cannot be excluded. We also studied the combination of a COX
      inhibitor with the IL-1 receptor antagonist protein. Consistent with earlier
      results, both the IL-1 receptor antagonist (IL-1ra) and indomethacin attenuated
      the hypophagic responses to LPS. Combination of the two treatments produced
      additive results almost completely preventing the hypophagic response. Because
      indomethacin almost completely prevented the hypophagic response to IL-1, this
      additivity suggests that there are multiple mechanisms by which LPS induces
      hypophagia.

PMID- 10970677
TI  - Higher natural killer cell activity in schizophrenic patients: the impact of
      serum factors, medication, and smoking.
AB  - Schizophrenia has been associated with altered immunity and reduced occurrence of
      autoimmune diseases and malignancies. A few studies in schizophrenic patients
      have assessed natural killer cell activity (NKA), but no consistent findings have
      emerged. However, NKA was assessed using standard procedures and in the absence
      of autologous serum and the various cytokines that modulate NKA and appear to be
      abnormal in schizophrenic patients. In the current study, therefore, the number
      of NK cells and the activity of the individual NK cell were assessed in whole
      blood shortly after blood withdrawal, in both the presence and the absence of
      autologous serum. Twenty-nine schizophrenic patients (11 nonmedicated), 8
      nonschizophrenic control patients (bipolar and personality disorders), and 31 age
      matched healthy controls were studied. Schizophrenic patients showed higher NKA
      per NK cell than controls and nonschizophrenic patients. This difference remained
      significant even when the nonmedicated schizophrenics, who showed the highest
      levels of NKA, were excluded. However, the increase in NKA was more pronounced in
      the presence of serum and was reduced to an insignificant level when serum was
      removed from the same samples. In both schizophrenic patients and controls,
      smokers and women showed lower NKA. Numbers of NK cells did not differ among
      groups, although medication affected blood concentration of other leukocytes.
      These findings indicate that the effects of serum factors, psychiatric
      medication, gender, and smoking should be considered when assessing NKA in
      schizophrenic patients. The observed higher NKA may help explain the surprising
      reports of low incidence of lung cancer and other malignancies in schizophrenic
      patients, despite their higher rate of smoking.

PMID- 10970678
TI  - Involvement of central mu- but not delta- or kappa-opioid receptors in
      immunomodulation.
AB  - Studies completed in both humans and animals have shown that opioids have
      significant effects on the immune system via pharmacological interactions with
      the opioid receptor. However, the type of opioid receptor at which morphine
      binding produces changes in immune status has not been well characterized. To
      determine the type of opioid receptor involved in opioid-induced immune
      alterations, the present study assessed the effects of agonists selective for the
      mu-, delta-, and kappa-opioid receptors. The site of action (i.e., peripheral vs
      central) at which opioids produce immune changes was investigated by injecting
      the agonists directly into the left lateral ventricle of the brain. Specifically,
      Lewis rats received an intracerebroventricular administration of [d-Ala(2),N-Me
      Phe(4), Gly-ol(5)]enkephalin (DAMGO), a mu-receptor selective agonist, [D
      Pen(2,5)]enkephalin (DPDPE), a delta-opioid receptor agonist, or U69,593, a kappa
      receptor agonist. Immune assessments completed 1 h following drug administration
      showed that the mu-receptor selective agonist DAMGO produced a dose-dependent
      decrease in natural killer cell activity and T-lymphocyte proliferation to the
      mitogen concanavalin A (Con A); no immunological changes were found following
      DPDPE or U69,593 treatment. Calculation of the number of white blood cells per
      sample showed no differences between rats treated with saline and rats treated
      with any of the selective agonists. Administration of the opioid antagonist N
      methylnaltrexone prior to DAMGO treatment attenuated the DAMGO-induced changes in
      immune status. Results from the present study indicate that the immunomodulatory
      effects of opioids can be attributed to interactions with the mu-opioid receptor.

PMID- 10970679
TI  - Pituitary involvement in T cell renewal during development and metamorphosis of
      Xenopus laevis.
AB  - Studies of pituitary-deficient dwarf mice show that in the absence of a normally
      functioning pituitary, thymus development is impaired. Treatment with growth
      hormone, prolactin, and thyroid hormones restores thymus development. Smaller
      thymus size in pituitary-deficient animals could be due to defective development
      of precursors, impaired precursor immigration, impaired thymocyte expansion, or
      development of a smaller epithelial/stromal compartment in the thymus of
      pituitary-deficient animals. Using a well-characterized amphibian model to study
      stem cell immigration into the thymus, we show here that hypophysectomy (hypx) of
      young tadpoles interferes with overall growth of the frogs and with the broad
      lymphocyte expansion that occurs after metamorphosis, but it does not interfere
      with the immigration of T cell precursors into an implanted thymus. Diploid host
      cells moving into a triploid thymus implant do so at the same rate and to the
      same extent in hypx hosts as they do in intact control hosts. Analysis of cell
      division in the implanted thymus populations shows a significantly greater
      proportion of cells arrested in the G(0)/G(1) phase and a significantly lower
      proportion of cells in the S phase and G(2) + M phase of the cell cycle in hypx
      hosts than in intact hosts. Thus, smaller thymus size in hypx hosts could be due
      to a slower rate of expansion of precursors that migrate there.

PMID- 10970680
TI  - Anticipatory symptoms and anticipatory immune responses in pediatric cancer
      patients receiving chemotherapy: features of a classically conditioned response?
AB  - There is considerable evidence from studies in adult patients that classical
      conditioning contributes to anticipatory nausea and/or vomiting (ANV) in cancer
      chemotherapy: The stimuli predicting the infusion serve as conditioned stimuli
      (CS). When reexposed to the CS, some patients experience ANV prior to infusion
      onset. In adult patients, anticipatory immunomodulation (AIM) has also been
      observed. The present study examines whether ANV and AIM occur in pediatric
      cancer patients and whether they show features of a conditioned response.
      METHODS: Nineteen pediatric cancer patients (M = 10.1 years, > 2 previous
      chemotherapies) were studied over two consecutive cycles (A, B). In both cycles,
      self-reported symptoms, for example nausea and vomiting, were recorded from two
      days prior to the onset (Day -2), during infusion, and two days after the end of
      the infusion (Day +2). In Cycle B, blood was drawn at home at Day -2, and at Day
      0 in the hospital prior to infusion onset, thus using a quasi-experimental
      variation of the CS content of the environment. Immune parameters valid for tumor
      defense and cytotoxic competence (natural killer cell activity [NKCA], plasma
      interleukin [IL]-1beta, IL-2, IL-10, interferon [IFN]-gamma, tumor necrosis
      factor [TNF]-alpha) and cortisol were measured. RESULTS: ANV was reported by 7
      patients in at least one cycle. In Cycle A, ANV was positively associated with
      emetogenity of chemotherapy. Features of ANV-duration and occurrence-tended to be
      positively associated with those of posttreatment nausea and vomiting. AN
      increased as infusion onset time approached. NKCA and IFN-gamma increased from
      home to hospital, independent from cortisol level. The NKCA increase was
      predominantly observed in patients with ANV. CONCLUSIONS: ANV in pediatric
      patients showed features of a CR. Immune parameters were sensitive to the CS
      content of the environment, predominantly in patients with ANV. This is
      consistent with the manifestation of multiple CRs.

PMID- 10970681
TI  - mRNA expression of serotonin receptors in cells of the immune tissues of the rat.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) has been shown to play a role in
      immunoregulation; however, little is known about specific subtypes of 5-HT
      receptors involved in peripheral immunomodulation. In the present study we used
      RT-PCR methods to examine the mRNA expression of 5-HT receptors in the cells of
      lymphoid tissues of the rat. All 13 rat 5-HT receptor genes cloned so far were
      examined in ex vivo isolated spleen, thymus, and peripheral blood lymphocytes, as
      well as in mitogen-stimulated spleen cells. Positive signals were obtained for 5
      HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT6, and 5-HT7 receptor mRNAs in all three
      compartments. Mitogen (ConA and PWM) stimulated cells additionally expressed mRNA
      corresponding to the 5HT-3 receptor subtype. In contrast, 5-HT1A, 5-HT1D, 5-HT2C,
      5-HT4, 5-HT5A, and 5-HT5B mRNAs were not detected in any of the examined cell
      populations. These results may be useful as a starting point for future
      functional studies on immunomodulatory effects of 5-HT and may help to understand
      conflicting serotonergic effects on immune functions as found in the literature.

PMID- 10970682
TI  - The illusion of cell immortality.
AB  - Normal cultured cell populations are mortal but cells that are immortal are
      abnormal and most have properties of cancer cells. Nevertheless, this distinction
      becomes blurred because the terms 'mortality' and 'immortality' are subject to
      enormous variations in understanding. Forty years ago we showed that cell
      mortality and immortality are inextricably linked to longevity determination,
      ageing and cancer. We suggested that a counting mechanism existed in normal cells
      and that has now been identified as telomere attrition. This replicometer, in
      combination with the discovery of the enzyme telomerase, has gone very far in
      explaining why most normal somatic cells have a finite capacity to replicate both
      in vivo and in vitro and how immortal cancer cells circumvent this inevitability.
      It is suggested that telomere attrition may be better understood as a direct
      measure of longevity determination and to only have an indirect association with
      age changes.

PMID- 10970683
TI  - Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin
      10 serum levels in patients with melanoma.
AB  - Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1
      (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers
      for melanoma progression. To evaluate the clinical relevance of these three
      markers, we simultaneously analysed their serum levels in patients with melanoma.
      A longitudinal study with a 3-year follow-up was performed and different stages
      of the disease were considered. Mean values of sIL-2R were significantly higher
      than in normal controls in all stages and correlated with the disease
      progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was
      significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of
      sICAM-1 were also elevated in melanoma patients, specially at the time of the
      metastatic disease. Serum IL-10 levels were more frequently detectable in the
      patients that developed metastasis during follow-up, and the prognosis of
      patients with detectable IL-10 levels was significantly poorer than in those
      patients with IL-10 undetected levels. Statistical analysis based on Logistic and
      Cox regression models showed that only sex, stage and sIL-2R value are factors
      significantly associated with metastatic progression. Moreover, high levels of
      sIL-2R could be a risk factor for malignant progression in melanoma.

PMID- 10970685
TI  - Controlling malignant pericardial effusion by intrapericardial carboplatin
      administration in patients with primary non-small-cell lung cancer.
AB  - Malignant pericarditis, when associated with massive pericardial effusion,
      presents a critical condition in lung cancer patients. Because this condition
      often arises in terminally ill patients, intensive therapy such as multi-drug
      combination chemotherapy is rarely appropriate. This study evaluated the clinical
      relevance of intrapericardial administration of carboplatin for controlling
      malignant pericardial effusions associated with non-small-cell lung carcinoma
      (NSCLC). The method used for 10 eligible patients consisted of draining the
      pericardial effusion and infusing 300 mg/body of carboplatin in 50 ml of saline
      through an in-place catheter into the pericardial space and clamping the catheter
      for 40 min. Nine of the 10 patients showed satisfactory results, and 8
      experienced complete regression of the effusion. No major or minor adverse
      effects were observed. Pharmacokinetics analysis revealed that the concentration
      of free platinum in the pericardial fluid was very high while that of total
      platinum in the circulating plasma was very low, assuring the usefulness of the
      intrapericardial instillation of carboplatin in terminally ill patients for
      controlling malignant pericardial effusion when the systemic delivery of
      cytotoxic agents is inappropriate.

PMID- 10970684
TI  - A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with
      chemotherapy in patients with advanced inoperable non-small-cell lung cancer and
      mesothelioma.
AB  - Mycobacterial preparations have been used with limited success against cancer
      apart from superficial bladder cancer. Recently, a therapeutic vaccine derived
      from Mycobacterium vaccae has been given to patients with prostate cancer and
      melanoma indicating a possible beneficial effect on disease activity in such
      patients. We have recently initiated a series of randomized studies to test the
      feasibility and toxicity of combining a preparation of heat-killed Mycobacterium
      vaccae (designated SRL172) with a multidrug chemotherapy regimen to treat
      patients with inoperable non-small cell lung cancer (NSCLC) and mesothelioma. 28
      evaluable patients with previously untreated symptomatic NSCLC and mesothelioma
      were randomized to receive either 3 weekly intravenous combination chemotherapy
      alone, or chemotherapy given with monthly intra-dermal injections of SRL172.
      Safety and tolerability were scored by common toxicity criteria and efficacy was
      evaluated by survival of patients and by tumour response assessed by CT scanning.
      The toxicity of chemotherapy was similar in the two groups. SRL172 caused mild
      inflammation at the injection site. In the group of patients randomized to
      receive chemotherapy combined with SRL172, there was a trend towards improved
      response rate (54% vs. 33%) with more patients in the combined arm receiving
      radical surgery and radiotherapy, improved median survival (9.7 months vs. 7.5
      months) and improved 1 year survival (42% vs. 18%). SRL172 appeared to improve
      sleep (P = 0.08) and improved appetite (P = 0.01). There was no detectable change
      in serum cytokine levels for gamma-interferon and TNF-alpha before and after
      treatment. In patients with NSCLC and mesothelioma, there may be a beneficial
      interaction when chemotherapy is administered in combination with SRL172.
      Confirmation of this effect and further investigation is underway in a randomized
      phase III trial and in laboratory models.

PMID- 10970687
TI  - Fascin, an actin-bundling protein associated with cell motility, is upregulated
      in hormone receptor negative breast cancer.
AB  - Loss of hormone receptor (HR) status in breast carcinomas is associated with
      increased tumour cell motility and invasiveness. In an immunohistological study
      of 58 primary breast cancers, oestrogen (ER) and progesterone (PR) receptor
      levels were inversely correlated with the expression of fascin, an actin-bundling
      protein associated with cell motility (P< 0.0001 and P = 0.0019, respectively).
      In addition, fascin was preferentially expressed in non-diploid tumours (P =
      0.03). In summary, the upregulation of fascin in HR-negative breast cancers may
      contribute to their more aggressive behaviour.

PMID- 10970686
TI  - Fluorodeoxyglucose positron emission tomography in the evaluation of germ cell
      tumours at relapse.
AB  - Differentiation of active disease from fibrosis/mature teratoma in patients with
      residual masses or identifying of sites of recurrence in patients with raised
      markers following treatment of their testicular cancer remains a problem.(18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to
      identify active disease and thereby influence further management in these
      patients. We performed a retrospective study of the use of FDG-PET in detecting
      residual/recurrent testicular carcinoma in 55 patients (seventy FDG-PET scans).
      Forty-seven scans were for the assessment of residual masses (18 had raised
      markers) and 23 scans were for the investigation of raised markers in the
      presence of normal CT scans. True positive results were based on positive
      histology or clinical follow-up. FDG-PET had a positive predictive value (PPV) of
      96% and a negative predictive value (NPV) of 90% in patients with residual
      masses. This PPV was equivalent to that of markers (94%) but FDG-PET had the
      advantage of identifying the site of that recurrence. The NPV was higher than
      that of markers. In patients with raised markers alone the PPV of FDG-PET was 92%
      but the NPV was only 50%. However, subsequent FDG-PET imaging was frequently the
      first imaging modality to identify the site of disease. FDG-PET effected a
      management change in 57% of cases. FDG-PET scanning detected viable tumour in
      residual masses and identified sites of disease in suspected recurrence.

PMID- 10970688
TI  - Expression of human milk fat globulin proteins in cells of haemopoietic origin.
AB  - Lineage-specific gene expression has been used for the identification of
      metastasis of cancers with unknown primary site or of disseminated cancer cells
      in haemopoietic compartments such as bone marrow or in lymph nodes. For the muc1,
      cytokeratin-19 and the CEA genes, the transcription in haemopoietic cells has
      been shown recently. Here, the expression of the mammary epithelium related
      antigens BA46 (lactadherin) and BA70 in lymphoid and myeloid cell lines, and in
      clinical specimens is analysed. By Northern-hybridization with specific
      oligonucleotides an ubiquitous transcription of both genes, independent from the
      provenance of cells or the chromosomal gender was found. Both mRNA molecules were
      amplified by rtPCR from the samples and the specificity could be confirmed by
      sequence analysis. Peptide-specific antibodies were raised in rabbits and used
      for Western-blot analysis and for immunocytochemical studies. Both antibodies
      reacted with total cell lysates from myeloid and lymphatic cells. In
      immunocytochemistry antibody P717 (anti-lactadherin) had a significant strong
      staining of the myeloid cell lines K562 and HL60 suggesting a participation of
      lactadherin in leukocyte-function. Using antibody P718, strong stains were seen
      in myeloid line K562 and lymphoid line ST486. In conclusion, our findings expand
      the results that the concept of lineage-specific gene expression is no longer
      valid at the molecular level.

PMID- 10970690
TI  - Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal
      cancer tissues.
AB  - Vascular endothelial growth factor-C (VEGF-C) functions specifically to induce
      lymphangiogenesis. We examined the relationship between expression of VEGF-C and
      clinicopathological features in patients with colorectal cancer. The expression
      of VEGF-C in the 99 primary tumours and 18 metastatic lymph nodes from colorectal
      cancer patients was examined immunohistochemically. To verify VEGF-C mRNA
      expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried
      out. The expression of VEGF-C correlated with lymphatic involvement, lymph nodes
      metastasis, and depth of invasion. On the other hand, correlations were nil with
      regard to gender of the patients, histologic type, venous involvement, and liver
      metastasis. The expression of VEGF-C in metastatic lymph nodes was fairly
      consistent with this expression in the primary tumour. Survival time was shorter
      for VEGF-C positive groups than for VEGF-C negative ones, but with no
      statistically significant difference. RT-PCR findings revealed that the
      expression of VEGF-C mRNA correlated mostly with that of VEGF-C protein
      expression. VEGF-C may play an important role in lymphatic spread of colorectal
      cancer.

PMID- 10970689
TI  - Expression of inducible nitric oxide synthase in healthy pleura and in malignant
      mesothelioma.
AB  - In this study we investigated the immunohistochemical expression of inducible
      nitric oxide synthase (iNOS) in a set of normal pleural mesothelial tissues,
      malignant mesotheliomas, mesothelioma cell lines and metastatic pleural
      adenocarcinomas. Furthermore, the expression of mRNA was assessed in four
      malignant mesothelioma cell lines in culture. Apoptosis and vascular density in
      malignant mesotheliomas was assessed by the TUNEL method and by
      immunohistochemistry with an antibody against FVIII-related antigen.
      Immunohistochemically mesothelial cells in non-neoplastic healthy pleural tissues
      were mostly negative for iNOS. Positivity for iNOS was observed in 28/38 (74%)
      and 24/25 (96%) of malignant mesotheliomas and metastatic pleural
      adenocarcinomas, respectively. Epithelial and mixed mesotheliomas expressed more
      often strong iNOS immunoreactivity compared to the sarcomatoid subtype (P =
      0.023). Moreover, metastatic adenocarcinomas expressed more often iNOS positivity
      than mesotheliomas (P = 0.021). Experiments with the cell lines confirmed that
      malignant mesothelioma cells are capable of synthesizing iNOS. No significant
      association was found between iNOS expression and apoptosis or vascular density
      in malignant mesotheliomas. The higher expression of iNOS in the epithelial
      subtype of mesothelioma and pleural metastatic adenocarcinoma might be due to an
      increased sensitivity of these cell types to cytokine-mediated iNOS upregulation.
      The strong expression of iNOS suggests a putative role for NO in the growth and
      progression of these tumours.

PMID- 10970691
TI  - MDR 1 activation is the predominant resistance mechanism selected by vinblastine
      in MES-SA cells.
AB  - Single-step selection with vinblastine was performed in populations of the human
      sarcoma cell line MES-SA, to assess cellular mechanisms of resistance to the drug
      and mutation rates via fluctuation analysis. At a stringent selection with 20 nM
      vinblastine, resulting in 5-6 logs of cell killing, the mutation rate was 7 x 10(
      7)per cell generation. Analysis of variance supported the hypothesis of
      spontaneous mutations conferring vinblastine resistance, rather than induction of
      adaptive response elements. Surviving clones displayed a stable multidrug
      resistance phenotype over a 3-month period. All propagated clones demonstrated
      high levels of resistance to vinblastine and paclitaxel, and lower cross
      resistance to doxorubicin and etoposide. Activation of MDR 1 gene expression and
      P-glycoprotein function was demonstrable in all clones. No elevation was found in
      the expression of the mrp gene, the LRP-56 major vault protein and beta-tubulin
      isotypes (M40, beta4, 5beta, and beta9) in these mutants. We conclude that
      initial-step resistant mechanism in these vinblastine-selected mutants commonly
      arises from a stochastic mutation event with activation of the MDR 1 gene.

PMID- 10970692
TI  - Use of thymidine analogues to indicate vascular perfusion in tumours.
AB  - Temporary reduction in blood-flow within tumour blood vessels can reduce oxygen
      supply leading to transient perfusion-limited hypoxia. Consequent selection of
      cells with mutations and reduced radiosensitivity can lead to disease progression
      and treatment-resistance. In the present study, we investigated whether
      heterogeneity of labelling after thymidine analogue administration is related to
      perfusion variations, and if so, could it be quantified and used as a perfusion
      indicator. Perfusion in murine RIF1 tumours was reduced by hydralazine or
      increased by nicotinamide and the mice subsequently injected with IdUrd. Tumours
      were halved for analysis by both flow cytometry and immunohistochemistry. Tumour
      sections were stained for vasculature and IdUrd. Each blood vessel was scored for
      the density of IdUrd-labelled cells surrounding it, using a semi-quantitative
      scoring system. Flow cytometry showed that the IdUrd labelling index and
      intensity decreased by approximately 50% after hydralazine. In tumour sections of
      control animals, 2.9% of vessels showed no IdUrd label. In contrast, after
      hydralazine almost 50% of vessels had no surrounding IdUrd labelling, whereas
      after nicotinamide there were fewer vessels with low labelling and a higher
      median score. In conclusion, changes of tumour perfusion by pharmacological
      agents is reflected in changes in tumour-cell labelling by the thymidine analogue
      IdUrd, suggesting that IdUrd labelling could be used to indicate perfusion in
      individual vessels in human tumours.

PMID- 10970693
TI  - Inhibition of growth of OV-1063 human epithelial ovarian cancers and c- jun and c
      fos oncogene expression by bombesin antagonists.
AB  - Receptors for bombesin are present on human ovarian cancers and bombesin-like
      peptides could function as growth factors in this carcinoma. Therefore, we
      investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists
      RC-3940-II and RC-3095 on the growth of human ovarian carcinoma cell line OV
      1063, xenografted into nude mice. Treatment with RC-3940-II at doses of 10 microg
      and 20 microg per day s.c. decreased tumour volume by 60.9% (P< 0.05) and 73.5%
      (P< 0.05) respectively, after 25 days, compared to controls. RC-3095 at a dose of
      20 microg per day reduced the volume of OV-1063 tumours by 47.7% (P = 0.15). In
      comparison, luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix
      at a dose of 100 microg per day caused a 64.2% inhibition (P< 0.05). RT-PCR
      analysis showed that OV-1063 tumours expressed mRNA for bombesin receptor
      subtypes BRS-1, BRS-2, and BRS-3. In OV-1063 cells cultured in vitro, GRP(14-27)
      induced the expression of mRNA for c- jun and c- fos oncogenes in a time
      dependent manner. Antagonist RC-3940-II inhibited the stimulatory effect of
      GRP(14-27) on c- jun and c- fos in vitro. In vivo, the levels of c- jun and c-
      fos mRNA in OV-1063 tumours were decreased by 43% (P< 0.05) and 45% (P = 0. 05)
      respectively, after treatment with RC-3940-II at 20 microg per day. Exposure of
      OV-1063, UCI-107 and ES-2 ovarian carcinoma cells to RC-3940-II at 1 microM
      concentration for 24 h in vitro, extended the latency period for the development
      of palpable tumours in nude mice. Our results indicate that antagonists of
      bombesin/GRP inhibit the growth of OV-1063 ovarian cancers by mechanisms that
      probably involve the downregulation of c- jun and c- fos proto-oncogenes.

PMID- 10970694
TI  - Carcinogenic effects of ptaquiloside in bracken fern and related compounds.
AB  - Consumption of the bracken fern Pteridium aquilinum by cattle has been shown to
      induce bladder and intestinal carcinomas in cattle and to cause a number of
      diseases in other farm animals. An unstable glucoside named ptaquiloside,
      containing a reactive cyclopropane ring, has been isolated from the fern and its
      potent carcinogenicity proven. Nineteen of 31 ferns tested by chemotaxonomic
      methods in Japan have been found to contain potentially carcinogenic
      ptaquilosides as have Cheilanthes sieberi and Pteridium esculentum. Hydrolysis of
      ptaquilosides leads to pterosins; under milder conditions a dienone which is
      believed to be the primary carcinogen is obtained. Hypacrone, a sesquiterpine
      containing a reactive cyclopropane ring, has been isolated from Hypolepis
      punctata and its structure proved by synthesis. Illudins, structurally similar to
      ptaquiloside, have been isolated from the basidiomycete Omphalotus illudens.
      These give anti-tumour activity and similar reactivity with nucleophiles to
      ptaquiloside. Compound CC-1065, a highly toxic antibiotic also containing a
      cyclopropane ring, has been isolated from Streptomyces zelensis. The mechanism of
      its reactivity with DNA has been compared to that of ptaquiloside and the small
      structural differences between carcinogenic and anti-tumour activity discussed.
      Both CC-1065 and adozelesin, a synthetic analogue with anti-tumour activity, have
      been shown to alkylate the N-3 atom of adenine in a certain sequence of DNA. The
      reactivity of cysteine with ptaquilosides and illudins is discussed, as is the
      role of cysteine alkylating agents in apoptosis.

PMID- 10970695
TI  - Drug resistance features and S-phase fraction as possible determinants for drug
      response in a panel of human ovarian cancer xenografts.
AB  - Multidrug resistance (MDR) and more specifically the expression of P-glycoprotein
      (Pgp) have been studied extensively in vitro. Unfortunately, it appears that the
      predictive value of MDR recognized in vitro is mostly an incorrect measure to
      determine the responsiveness of a particular tumour in the clinic. This
      misunderstood or overvalued role of MDR might explain the failure of strategies
      to reverse Pgp function by the use of modulators in solid tumours. To obtain more
      insight in in vivo drug resistance we investigated a panel of 15 human ovarian
      cancer xenografts consisting of the most common histological subtypes known in
      ovarian cancer patients. The response rate to cisplatin, cyclophosphamide and
      doxorubicin in the xenografts resembled the results of phase II trials with these
      agents in ovarian cancer patients. This resemblance justifies drug resistance
      studies in this experimental in vivo human tumour system. We determined the
      expression levels of MDR 1, MRP 1, LRP and topoisomerase IIalpha mRNA by the
      RNase protection assay and the presence of MRP1 and LRP proteins by
      immunohistochemistry. The S-phase fraction was investigated as a separate
      parameter by flow cytometry. In none of the 15 ovarian cancer xenografts was MDR
      1 expression detectable. The expression levels of MRP 1 and LRP were low to
      moderate and resembled the presence of the MRP1 and LRP proteins. There was a
      weak, inverse relationship between the expression levels of LRP and sensitivity
      to cisplatin and cyclophosphamide (r = -0.44 and -0.45), but not to doxorubicin.
      The levels of topoisomerase IIalpha varied among the xenografts (0.73-2.66) and
      failed to correlate with doxorubicin resistance (r = 0.14). The S-phase fraction,
      however, showed a relation with the sensitivity to cisplatin (r = 0.66). Among
      the determinants studied in ovarian cancer in vivo, LRP mRNA and the S-phase
      fraction were the best predictive factors for drug response and most specifically
      for the activity of cisplatin.

PMID- 10970697
TI  - Pulmonary availability of isotretinoin in rats after inhalation of a powder
      aerosol.
AB  - Repeated oral administration of chemopreventive retinoids such as isotretinoin
      over extended periods of time is associated with intolerable systemic toxicity.
      Here isotretinoin was formulated as a powder aerosol, and its delivery to the
      lungs of rats was studied with the aim to explore the possibility of minimizing
      adverse effects associated with its oral administration. Rats received
      isotretinoin orally (0.5, 1 or 10 mg kg(-1)) or by inhalation (theoretical dose
      approximately 1 or approximately 10 mg kg(-1)) in a nose-only inhalation chamber.
      Isotretinoin was quantitated by high-pressure liquid chromatography in plasma and
      lung tissue. The ratios of mean area of concentration-vs-time curve (AUC) values
      in the lungs over mean AUCs in the plasma for isotretinoin following single or
      repeated aerosol exposure surpassed those determined for the oral route by
      factors of between two (single low-dose) and five (single high-dose). Similarly,
      the equivalent ratios for the maximal peak concentrations in lungs and plasma
      obtained after aerosol exposure consistently exceeded those seen after oral
      administration, suggesting that lungs were exposed to higher isotretinoin
      concentrations after aerosol inhalation than after oral administration of similar
      doses. Repeated high doses of isotretinoin by inhalation resulted in moderate
      loss of body weight, but microscopic investigation of ten tissues including lung
      and oesophagus did not detect any significant aerosol-induced damage. The results
      suggest that administration of isotretinoin via powder aerosol inhalation is
      probably superior to its application via the oral route in terms of achieving
      efficacious drug concentrations in the lungs.

PMID- 10970696
TI  - Suppression of manganese superoxide dismutase augments sensitivity to radiation,
      hyperthermia and doxorubicin in colon cancer cell lines by inducing apoptosis.
AB  - Increased expression of manganese superoxide dismutase (Mn-SOD), one of the
      mitochondrial enzymes involved in the redox system, has been shown to diminish
      the cytotoxic effects of several anti-cancer modalities, including tumour
      necrosis factor-alpha, ionizing radiation, certain chemotherapeutic agents and
      hyperthermia. We asked if Mn-SOD is a potential target to augment the sensitivity
      of cancer cells to various anti-cancer treatments and for this we established
      stable Mn-SOD antisense RNA expressing cell clones from two human colon cancer
      cell lines, HCT116 (p53 wild-type) and DLD1 (p53 mutant-type). Suppression of Mn
      SOD in HCT116 was accompanied by an increased sensitivity to radiation,
      hyperthermia and doxorubicin, as compared with findings in controls. The
      mitochondrial permeability transition, as measured by a decrease of the
      mitochondrial transmembrane potential was more intensely induced by radiation in
      HCT116 antisense clones than in the control, an event followed by a greater
      extent of DNA fragmentation. Apoptosis was also induced by hyperthermia more
      intensely in HCT116 antisense clones than in the control. On the other hand, DLD1
      antisense clones did not exhibit any enhancement of sensitivity to any of these
      treatments. These data support the possibility that inhibition of Mn-SOD activity
      renders colon cancer cells with wild-type p53 susceptible to apoptosis induced by
      radiation, hyperthermia and selected anti-cancer drugs. Therefore, we suggest
      that Mn-SOD could be a target molecule to overcome the resistance to anti-cancer
      treatments in some colon cancer cells carrying wild-type p53.

PMID- 10970699
TI  - Alcohol and breast cancer risk: the alcoholism paradox.
AB  - A population-based cohort study of 36 856 women diagnosed with alcoholism in
      Sweden between 1965 and 1995 found that alcoholic women had only a small 15%
      increase in breast-cancer incidence compared to the general female population. It
      is therefore apparent, contrary to expectation, that alcoholism does not increase
      breast-cancer risk in proportion to presumed ethanol intake.

PMID- 10970698
TI  - [Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (antagonist G) induces AP-1
      transcription and sensitizes cells to chemotherapy.
AB  - [Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (antagonist G) inhibits
      small cell lung cancer (SCLC) growth and is entering Phase II clinical
      investigation for the treatment of SCLC. As well as acting as a neuropeptide
      receptor antagonist, antagonist G stimulates c-jun-N-terminal kinase (JNK)
      activity and apoptosis in SCLC cells. We extend these findings and show that the
      stimulation of JNK and apoptosis by antagonist G is dependent upon the generation
      of reactive oxygen species (ROS) being inhibited either by anoxia or the presence
      of N-acetyl cysteine (n-AC). Antagonist G is not intrinsically a free radical
      oxygen donor but stimulates free radical generation specifically within SCLC
      cells (6.2-fold) and increases the activity of the redox-sensitive transcription
      factor AP-1 by 61%. In keeping with this, antagonist G reduces cellular
      glutathione (GSH) levels (38% reduction) and stimulates ceramide production and
      lipid peroxidation (112% increase). At plasma concentrations achieved clinically
      in the phase I studies, antagonist G augments, more than additively, growth
      inhibition induced by etoposide. Our results suggest that antagonist G may be
      particularly effective as an additional treatment with standard chemotherapy in
      SCLC. These novel findings will be important for the clinical application of this
      new and exciting compound and for the future drug development of new agents to
      treat this aggressive cancer.

PMID- 10970700
TI  - Epidemiology of carcinoid neoplasms in Vaud, Switzerland, 1974-97.
AB  - In Vaud, Switzerland, the incidence of carcinoids based on 218 malignant and 215
      benign cases rose from 19.6/10(6)in 1974-85 to 28. 2/10(6)in 1986-97, more so
      among males and malignant neoplasms. Lung was the commonest site for malignant
      and large intestine for benign carcinoids. Sixty-eight (16%) carcinoids had
      another neoplasm.

PMID- 10970701
TI  - Haemophilus influenzae type B vaccination and risk of childhood leukaemia in a
      vaccine trial in Finland.
AB  - Incidence of childhood leukaemia was studied among subjects of a trial comparing
      administration of several doses of a conjugate vaccine against Haemophilus
      influenzae type b (Hib) starting at an early age (three months) with a single
      dose given at the age of two years. Among 114 000 subjects, a total of 77 cases
      of childhood leukaemia were detected. The incidence of childhood leukaemia was
      lower in the early vaccination arm (relative risk 0.72, 95% confidence interval
      0.46-1.13) than late vaccination arm, but the difference did not reach
      statistical significance. Our results suggest that early immunization against Hib
      may reduce the incidence of childhood leukaemia, but confirmatory studies are
      needed.

PMID- 10970702
TI  - Sample sizes for cancer trials where Health Related Quality of Life is the
      primary outcome.
AB  - Health Related Quality of Life (HRQoL) instruments are increasingly important in
      evaluating health care, especially in cancer trials. When planning a trial, one
      essential step is the calculation of a sample size, which will allow a reasonable
      chance (power) of detecting a pre-specified difference (effect size) at a given
      level of statistical significance. It is almost mandatory to include this
      calculation in research protocols. Many researchers quote means and standard
      deviations to determine effect sizes, and assume the data will have a Normal
      distribution to calculate their required sample size. We have investigated the
      distribution of scores for two commonly used HRQoL instruments completed by lung
      cancer patients, and have established that scores do not have the Normal
      distribution form. We demonstrate that an assumption of Normality can lead to
      unrealistically sized studies. Our recommendation is to use a technique that is
      based on the fact that the HRQoL data are ordinal and makes minimal but realistic
      assumptions.

PMID- 10970703
TI  - Birthweight, childhood growth and risk of breast cancer in a British cohort.
AB  - We have examined the relationship between birthweight and risk of breast cancer,
      taking into account growth in childhood, using data on a total of 2221 women born
      in 1946 and followed up to 1997. Thirty-seven breast cancers occurred during
      follow-up. There was evidence of greater risk of breast cancer with greater
      birthweight (rate ratio = 1.76 (95% CI: 0.92, 3.35) for birthweight >/= 3.5 kg vs
      birthweight < 3.5 kg), which was more marked at pre-menopausal ages (RR = 2.31,
      95% CI: 0.93, 5.74). The relation with birthweight was not substantially
      confounded by any of the measured adult risk factors. A significant interaction
      was observed between the effects of birthweight and height at age 7 years.
      Relative to those born lighter than 3.5 kg, women who were heavy at birth (>/=
      3.5 kg) and short or average at 7 years (< 1.22 m) had a 21% increase in breast
      cancer rates (RR = 1.21; 95% CI = 0.49-2.99), while women who were heavy at birth
      (>/= 3.5 kg) but tall at 7 years (>/= 1.22 m) had a four-fold increase (RR =
      4.01; 95% CI = 1.82-8.83). These results suggest that the effect of birthweight
      on breast cancer risk may be modulated by childhood growth.

PMID- 10970704
TI  - Helicobacter pylori and gastric carcinoma: potential carcinogen, cancer sentinel,
      or both?

PMID- 10970705
TI  - Estimating the contribution of Helicobacter pylori to gastric cancer.

PMID- 10970706
TI  - Fatty acid metabolism in neurodevelopmental disorder: a new perspective on
      associations between attention-deficit/hyperactivity disorder, dyslexia,
      dyspraxia and the autistic spectrum.
AB  - There is increasing evidence that abnormalities of fatty acid and membrane
      phospholipid metabolism play a part in a wide range of neurodevelopmental and
      psychiatric disorders. This proposal is discussed here in relation to attention
      deficit/hyperactivity disorder (ADHD), dyslexia, developmental coordination
      disorder (dyspraxia) and the autistic spectrum. These are among the most common
      neurodevelopmental disorders of childhood, with significant implications for
      society as well as for those directly affected. However, controversy still
      surrounds both the identification and management of these conditions, and while
      their aetiology is recognized as being complex and multifactorial, little
      progress has yet been made in elucidating predisposing factors at the biological
      level. An overview is provided here of the contents of this Special Issue, which
      contains a selection of reports from a unique multidisciplinary workshop
      involving both researchers and clinicians. Its purpose was to explore the
      possibility that ADHD, dyslexia, dyspraxia and autism fall within a phospholipid
      spectrum of disorders. This proposal could explain the high degree of co
      morbidity between these conditions, their aggregation within families and
      relation to other psychiatric disorders, and a range of associated features that
      are already well known at a clinical level. The existing evidence for fatty acid
      abnormalities in these disorders is summarized, and new approaches are outlined
      that have the potential to improve both the identification and the management of
      these and related neurodevelopmental and psychiatric conditions.

PMID- 10970707
TI  - Epidemiology of neurodevelopmental disorders in children.
AB  - The epidemiology of mental and behavioural disorders is considered in comparison
      with spina bifida, chromosomal anomalies and brain tumours. Descriptive
      epidemiology is important not only in assessing the frequency of
      neurodevelopmental disorders, thereby aiding planning of service provision, but
      also because variations by geographical area, over time, and by personal
      characteristics provide clues regarding etiology. The value of the latter
      application is exemplified by research on spina bifida and other neural tube
      defects (NTDs). The descriptive epidemiology of mental and behavioural disorders
      has been less investigated. The descriptive epidemiology of NTDs suggested that
      diet might be of etiological importance. Analytical epidemiologic investigation
      proceeded by testing dietary hypotheses in case-control and cohort studies.
      Subsequently, folate supplementation was shown to reduce recurrence risk in a
      randomized controlled trial. The analytical epidemiology of other
      neurodevelopmental disorders is less well understood. Study design issues are
      discussed in relation to mental and behavioural disorders.

PMID- 10970708
TI  - Red blood cell fatty acid compositions in a patient with autistic spectrum
      disorder: a characteristic abnormality in neurodevelopmental disorders?
AB  - The fatty acid compositions of red blood cell (RBC) phospholipids from a patient
      with autistic spectrum disorder (ASD) had reduced percentages of highly
      unsaturated fatty acids (HUFA) compared to control samples. The percentage of
      HUFA in the RBC from the autistic patient was dramatically reduced (up to 70%)
      when the sample was stored for 6 weeks at -20 degrees C. However, only minor HUFA
      reductions were recorded in control samples stored similarly, or when the
      autistic sample was stored at -80 degrees C. A similar instability in RBC HUFA
      compositions upon storage at -20 degrees C has been recorded in schizophrenic
      patients. In a number of other neurodevelopmental conditions, including attention
      deficit hyperactivity disorder (ADHD) and dyslexia, reduced concentrations of RBC
      HUFA have been recorded. The extent and nature of these aberrations require
      further assessment to determine a possible common biochemical origin of
      neurodevelopmental disorders in general. To facilitate this, a large scale
      assessment of RBC fatty acid compositions in patients with ASD, and related
      disorders, should be performed as a matter of urgency. Supplementing cells in
      culture with the tryptophan metabolite indole acrylic acid (IAA) affected the
      levels of cellular HUFA and prostaglandin production. Indole acroyl glycine
      (IAG), a metabolite of IAA excreted in urine, is found in high concentrations in
      patients with neurodevelopmental disorders including ASD, ADHD, dyslexia,
      Asperger's syndrome and obsessive compulsive disorder.

PMID- 10970709
TI  - A sibling-pair based approach for mapping genetic loci that influence
      quantitative measures of reading disability.
AB  - Family and twin studies consistently demonstrate a significant role for genetic
      factors in the aetiology of the reading disorder dyslexia. However, dyslexia is
      complex at both the genetic and phenotypic levels, and currently the nature of
      the core deficit or deficits remains uncertain. Traditional approaches for
      mapping disease genes, originally developed for single-gene disorders, have
      limited success when there is not a simple relationship between genotype and
      phenotype. Recent advances in high-throughput genotyping technology and
      quantitative statistical methods have made a new approach to identifying genes
      involved in complex disorders possible. The method involves assessing the genetic
      similarity of many sibling pairs along the lengths of all their chromosomes and
      attempting to correlate this similarity with that of their phenotypic scores. We
      are adopting this approach in an ongoing genome-wide search for genes involved in
      dyslexia susceptibility, and have already successfully applied the method by
      replicating results from previous studies suggesting that a quantitative trait
      locus at 6p21.3 influences reading disability.

PMID- 10970710
TI  - Autistic spectrum disorder: diagnostic difficulties.
AB  - Recognition of the autistic spectrum disorders is becoming more widespread
      amongst basic scientists, clinicians, and the general population. The term does
      not imply anything about pathology or aetiology, although it has proved to be a
      useful concept clinically. From Kanner's classical autism the concept has widened
      in scope to include milder and more subtle impairments. From a clinical
      perspective, there are many alternative diagnoses in an individual with autistic
      like symptoms, and thorough investigation is necessary to exclude these.

PMID- 10970711
TI  - Increased levels of cytosolic phospholipase A2 in dyslexics.
AB  - Research findings are increasingly reporting evidence of physiological
      abnormalities in dyslexia and sites for dyslexia have been identified on three
      chromosomes. It has been suggested that genetic inheritance may cause
      phospholipid abnormalities in dyslexia somewhat similar to those found in
      schizophrenia. A key enzyme in phospholipid metabolism, Type IV, or cytosolic,
      phospholipase A2 (cPLA2), releases arachidonic acid (AA), a 20-carbon fatty acid,
      which is the major source of production of prostaglandins and leukotrienes. An
      entirely new assay, which for the first time has enabled determination of the
      amount of the enzyme rather than its activity, was used to measure cPLA2 in
      dyslexic-type adults and controls and the two groups were found to differ
      significantly, the dyslexic-types having more of the enzyme. A report elsewhere
      of schizophrenics having even greater amounts of the enzyme suggests that
      dyslexia may be on a continuum with schizophrenia, as may be other
      neurodevelopmental disorders - which have also been described as phospholipid
      spectrum disorders.

PMID- 10970712
TI  - Autism as a neurodevelopmental disorder affecting communication and learning in
      early childhood: prenatal origins, post-natal course and effective educational
      support.
AB  - Colwyn Trevarthen, working on autism, discussed the importance of time, rhythm
      and temporal processing in brain function. The brains of new born infants show
      highly coherent and coordinated patterns of activity over time, and their rhythms
      are remarkably similar to those of adults. Since the cortex has not yet
      developed, this coordination must be subcortical in origin. The likely source is
      the emotional motor system. He noted that the cerebellum might regulate the
      intricate timing of the development and expression of emotional communication. He
      also pointed out that emotional and motivational factors have often been
      seriously neglected in psychology (largely owing to a misplaced focus on
      'cognition' as some isolated entity) and emphasized the potential importance of
      empathetic support and music therapy in helping autistic children.

PMID- 10970713
TI  - Gene targets related to phospholipid and fatty acid metabolism in schizophrenia
      and other psychiatric disorders: an update.
AB  - Phospholipids make up about 60% of the brain's dry weight and play key roles in
      many brain signal tranduction mechanisms. A recent review(1)identified the
      increasing evidence that abnormal phospholipid and related fatty acid metabolism
      may contribute to illnesses such as schizophrenia, bipolar disorder, depression
      and attention deficit hyperactivity disorder. This current paper reviews the main
      pathways of phospholipid metabolism, emphasizing the role of phospholipases of
      the A2 in signal tranduction processes. It also updates the chromosomal locations
      of regions likely to be involved in these disorders, and relates these to the
      known locations of genes directly or indirectly involved in phospholipid and
      fatty acid metabolism.

PMID- 10970714
TI  - Could oxidative stress be a factor in neurodevelopmental disorders?
AB  - There is evidence of co-morbidity in the neurodevelopmental disorders and they
      display depletion of polyunsaturated fatty acids (PUFAs) in their plasma and red
      cell membranes. This suggests an abnormal fatty acid metabolism, which may affect
      cell signalling and synthesis of eicosanoids. This common feature in the
      neurodevelopmental disorders may be genetic in origin: however, oxidative stress
      may also contribute to decreased PUFAs found in these disorders.

PMID- 10970715
TI  - Potential diagnostic aids for abnormal fatty acid metabolism in a range of
      neurodevelopmental disorders.
AB  - Disorders of neurodevelopment include attention deficit hyperactivity disorder,
      dyspraxia, dyslexia and autism. There is considerable co-morbidity of these
      disorders and their identification often presents difficulties to those making a
      diagnosis. This is especially difficult when a multidisciplinary approach is not
      adopted. All of these disorders have been reported as associated with fatty acid
      abnormalities ranging from genetic abnormalities in the enzymes involved in
      phospholipid metabolism to symptoms reportedly improved following dietary
      supplementation with long chain fatty acids. If definitive disorders of lipid
      metabolism could be defined then the diagnosis and subsequent management of
      neurodevelopmental disorders might be transformed. In the identification of those
      disorders of development which involve lipid metabolism, there are now several
      tests, measures of lipid metabolism, which could be useful.

PMID- 10970716
TI  - Fatty acid deficiency signs predict the severity of reading and related
      difficulties in dyslexic children.
AB  - It has been proposed that developmental dyslexia may be associated with relative
      deficiencies in certain highly unsaturated fatty acids (HUFA). In children with
      attention-deficit/hyperactivity disorder, minor physical signs of fatty acid
      deficiency have been shown to correlate with blood biochemical measures of HUFA
      deficiency. These clinical signs of fatty acid deficiency were therefore examined
      in 97 dyslexic children in relation to reading and related skills, and possible
      sex differences were explored. Children with high fatty acid deficiency ratings
      showed poorer reading (P<0.02) and lower general ability (P<0.04) than children
      with few such clinical signs. Within males (n=72) these relationships were
      stronger, and fatty acid deficiency signs were also associated with poorer
      spelling and auditory working memory (P<0.05, P<0.005 respectively). Within
      females (n=25) no associations were significant. These results support the
      hypothesis that fatty acid deficiency may contribute to the severity of dyslexic
      problems, although sex differences merit further investigation.

PMID- 10970717
TI  - Dyslexia in adults is associated with clinical signs of fatty acid deficiency.
AB  - Developmental dyslexia is a complex syndrome whose exact cause remains unknown.
      It has been suggested that a problem with fatty acid metabolism may play a role,
      particularly in relation to the visual symptoms exhibited by many dyslexics. We
      explored this possibility using two self-report questionnaires, designed on the
      basis of clinical experience, to assess (1) clinical signs of fatty acid
      deficiency; and (2) symptoms associated with dyslexia in known dyslexic and non
      dyslexic subjects. Dyslexic signs and symptoms included the auditory-linguistic
      and spoken language difficulties traditionally associated with the disorder, as
      well as visual problems (both with reading and more generally) and motor
      problems. Fatty acid deficiency signs were significantly elevated in dyslexic
      subjects relative to controls, particularly within males (P<0.001). In addition,
      the severity of these clinical signs of fatty acid deficiency was strongly
      correlated with the severity of dyslexic signs and symptoms not only in the
      visual domain, but also with respect to auditory, linguistic and motor problems.
      The pattern of relationships differed somewhat between dyslexic and control
      groups, and sex differences were also observed. Our findings support the
      hypothesis that fatty acid metabolism may be abnormal in developmental dyslexia,
      and indicate the need for further studies using more objective measures.

PMID- 10970718
TI  - The potential role of fatty acids in attention-deficit/hyperactivity disorder.
AB  - As currently defined, attention-deficit/hyperactivity disorder (ADHD) encompasses
      a broad constellation of behavioural and learning problems and its definition and
      diagnosis remain controversial. The aetiology of ADHD is acknowledged to be both
      complex and multifactorial. The proposal considered here is that at least some
      features of ADHD may reflect an underlying abnormality of fatty acid metabolism.
      Clinical and biochemical evidence is discussed which suggests that a functional
      deficiency of certain long-chain polyunsaturated fatty acids could contribute to
      many of the features associated with this condition. The implications in terms of
      fatty acid treatment proposals are also discussed; such a form of treatment is
      relatively safe compared to existing pharmacological interventions, although
      further studies are still needed in order to evaluate its potential efficacy in
      the management of ADHD symptoms.

PMID- 10970719
TI  - Visual function, fatty acids and dyslexia.
AB  - There is mounting evidence that developmental dyslexia is a neurodevelopmental
      disorder which involves abnormalities of fatty acid metabolism, particularly with
      respect to certain long-chain highly unsaturated fatty acids (HUFAs).
      Psychophysical evidence also strongly suggests that dyslexics may have visual
      deficits as well as phonological problems. Specifically, these visual deficits
      appear to be related to the magnocellular pathway, which is specialized for
      processing fast, rapidly-changing information about the visual scene. It remains
      unclear how these two aspects of dyslexia - fatty acid processing and visual
      magnocellular function - could be related. We propose some hypotheses -
      necessarily speculative, given the paucity of biochemical research in this field
      to date - which address this question.

PMID- 10970720
TI  - The role of long-chain polyunsaturated fatty acids in infant cognitive
      development.
AB  - Dietary long-chain polyunsaturated fatty acids (LCPUFA) in infancy are necessary
      for normal brain growth and development, and may play an important role in the
      development of infant cognition. Several randomized, controlled studies have
      evaluated the effects of feeding both term and preterm infants formula containing
      LCPUFA or no LCPUFA on a variety of measures of cognitive behaviour. Studies of
      the relation of LCPUFA to performance on tests of psychomotor development have
      produced inconsistent results, with supplemented infants demonstrating either
      higher scores or no differences in comparison to controls. This pattern suggests
      that global tests of development may be insufficiently sensitive for detecting
      the effects of LCPUFA on infant cognitive function. In contrast, studies
      assessing the influence of LCPUFA on development of specific cognitive behaviours
      have shown a significant advantage for supplemented infants on measures of visual
      attention and problem solving. These results suggest that LCPUFA may enhance more
      efficient information processing or attention regulation in infants. Whether
      there are any long-term effects of dietary LCPUFA in infancy on childhood
      cognition is not known.

PMID- 10970722
TI  - The neurobiology of reading difficulties.

PMID- 10970721
TI  - Genetics of specific language impairment.

PMID- 10970723
TI  - Rapid identification of Pseudomonas aeruginosa from ocular isolates by PCR using
      exotoxin A-specific primers.
AB  - The purpose of this research was to evaluate the use of PCR for the
      identification of ocular isolates of Pseudomonas aeruginosa by using primers
      specific to the exotoxin A gene of the bacteria. Genomic DNA was obtained from
      ocular microbial isolates of keratitis patients. Primers were designed based on
      the published sequence of the exotoxin A gene of P. aeruginosa. Using the primers
      designed, PCR reactions were performed on the DNA samples. The PCR was also
      examined for its specificity and sensitivity. In addition, a direct PCR using
      heating method was attempted on P. aeruginosa with no separate DNA extraction
      step. ATCC strains of P. aeruginosa were included as positive controls. The rest
      of the bacteria other than P. aeruginosa served as negative controls. A single
      band was obtained when analysed on agarose gel electrophoresis only from samples
      that contained genomic DNA of P. aeruginosa. The direct PCR method was also
      successful with the same band produced from the amplification. The whole process
      was completed within 4 h. The direct PCR amplification targeting at the exotoxin
      A gene of P. aeruginosa is potentially a rapid, specific, sensitive and
      relatively simple method for the identification of ocular isolates of P.
      aeruginosa.

PMID- 10970724
TI  - Specific PCR identification of the T1 vaccine strains for contagious bovine
      pleuropneumonia.
AB  - A specific PCR test for the identification of the vaccine strains T1, T1/44 and
      T1sr, was developed. This PCR reaction is based on variations of DNA sequences in
      a region flanking one IS1296 copy. The specific primer pair MmmSCP1-T1M2
      amplifies a 700-bp long DNA fragment in the T1 vaccine strains and gives no
      amplification with the 60 other Mycoplasma mycoides subsp. mycoides SC strains
      tested. This PCR will permit to distinguish the T1 strain from all other vaccine
      strains and therefore avoid possible confusions. In addition, it should enable
      better investigations of post-vaccinal reactions.

PMID- 10970725
TI  - Comparison of telomerase activity and GSTP1 promoter methylation in ejaculate as
      potential screening tests for prostate cancer.
AB  - New diagnostic tools are needed for the early detection of prostatic cancer. The
      molecular detection of prostate cancer cells in ejaculates was evaluated using
      complementary PCR-based methods. LNCaP cells, a cell line derived from prostatic
      carcinoma, were spiked into normal seminal ejaculates and the prostatic
      epithelial component of the specimens was isolated by immunomagnetic bead
      sorting, using a monoclonal antibody to prostate-specific membrane antigen
      (PSMA). Ejaculates from nine patients with a recent diagnosis of prostate cancer
      were processed in a similar fashion, using LNCaP-spiked aliquots as an internal
      positive control. Telomerase expression was evaluated by the telomeric repeat
      amplification protocol (TRAP) and glutathione S-transferase gene promoter (GSTP1)
      hypermethylation was evaluated by methylation-sensitive restriction endonuclease
      digestion and PCR amplification. Telomerase activity was detected in LNCaP cells
      recovered from normal seminal ejaculates but was not found in all nine samples
      from patients with prostate cancer. The sensitivity of GSTP1 analysis was similar
      to telomerase analysis for the detection of LNCaP cells from normal ejaculate
      samples but was positive in ejaculates from four out of nine patients with
      prostate cancer. GSTP1 DNA methylation status is more sensitive than telomerase
      analysis for the detection of malignant cells in seminal ejaculates from patients
      with prostate cancer.

PMID- 10970726
TI  - Quality control and optimized procedure of hybridization capture-PCR for the
      identification of Mycobacterium avium subsp. paratuberculosis in faeces.
AB  - Nucleic acid sequence capture techniques are used to improve both the sensitivity
      and specificity of PCR for the diagnosis of plant, animal and human diseases.
      Hybridization capture-PCR (HC-PCR) was first reported as a method for the
      detection of Mycobacterium avium subsp. paratuberculosis in 1995 and was
      successfully trialed on a small number of faecal samples from cattle with Johne's
      disease. A locally optimized HC-PCR method was evaluated on faeces from infected
      and non-infected animals. However, sample to sample cross contamination during
      the DNA purification step highlighted that the original format of the test was
      unsuitable for routine diagnostic use. Here, we report modifications and
      optimization of HC-PCR, particularly with respect to DNA purification from
      faeces, hybridization and capture steps. We also identified procedurally
      sensitive critical points in the test during capture and washing of magnetic
      beads. Southern blotting was omitted from the protocol to preserve specificity
      but this resulted in analytical sensitivity of 5000 organisms per 200 mg faecal
      sample. Nevertheless, HC-PCR detected M.paratuberculosis in pellets from infected
      sheep diluted at rates of up to 1 in 100 in normal faeces, suggesting that the
      technique should be evaluated further for low-cost diagnosis in flocks/herds
      using pooled samples.

PMID- 10970727
TI  - Rapid detection of Campylobacter fetus by polymerase chain reaction combined with
      non-radioactive hybridization using an oligonucleotide covalently bound to
      microwells.
AB  - Campylobacter fetus is recognized as a human and animal pathogen. The isolation
      and differentiation of C. fetus in diagnostic laboratories is hindered by its
      relatively slow growth and lack of distinguishing biochemical characteristics. We
      cloned and sequenced a 1581-bp DNA fragment, IG02, isolated from a C. fetus
      genomic library. This fragment was used as a probe on DNAs extracted from C.
      fetus strains and other Campylobacter species: IG02 hybridized only with DNAs
      from C. fetus strains. A PCR-based test was developed for the detection of C.
      fetus. A pair of oligonucleotide primers was designed to amplify a 141-bp
      fragment of IG02. The amplified product was analysed by a non-radioactive
      sandwich hybridization in microtiter plate using a capture oligonucleotide and a
      biotin-labelled oligonucleotide for the detection. The combination of PCR and non
      radioactive microplate hybridization is a convenient method for the rapid
      detection of C. fetus.

PMID- 10970728
TI  - Cloning of a gene from Mycobacterium tuberculosis coding for a hypothetical 27
      kDa protein and its use for the specific PCR identification of these
      mycobacteria.
AB  - PCR targeting the IS 6110 has been considered specific for identification of
      Mycobacterium tuberculosis and is frequently applied to confirm the presence of
      this organism directly in biological specimens. However, several authors found
      that some M. tuberculosis strains failed to hybridize with the IS 6110 probe and
      other authors found that false-positive results may be obtained for clinical
      samples when some methods based on IS 6110 are used. In the present study, the
      p27 gene isolated from a cosmid library was found to be highly specific for M.
      tuberculosis complex strains and allowed us to develop a PCR-based assay for
      rapid detection and identification of this mycobacterium. One pair of primers and
      two oligonucleotide probes were successfully used to amplify and to detect the
      DNA of strains belonging to the M. tuberculosis complex. These primers and probes
      did not hybridize with DNA from any of the 21 other mycobacterial species tested.
      It is worth noting that the chosen primers and probes hybridize with DNA from the
      M. tuberculosis strain with no IS 6110, furthermore no strain without p27 was
      found among the 410 strains tested in the present study.

PMID- 10970729
TI  - Factor V Leiden genotyping using real-time fluorescent polymerase chain reaction.
AB  - A fluorogenic probe-based PCR assay (Taqman; Perkin Elmer corp/Applied
      Biosystems, Foster City, CA, USA) was used for the detection of Factor V Leiden,
      a point mutation in the factor V gene (G1691A) that is the most common inherited
      risk factor for Deep Vein Thrombosis. This assay allows for the direct detection
      of specific PCR products within minutes of completion of the PCR by monitoring
      the increase in fluorescence of a dye-labelled oligonucleotide probe. Two dye
      labelled probes are used in this allelic discrimination assay, one probe for each
      allele in the two-allele system. Each probe consists of an oligonucleotide with a
      5'-reporter dye and a 3'-quencher dye. Tet (6-carboxy-4,7,2',7'-tetrachloro
      fluorescein) is covalently linked to the 5'-end of the probe for the detection of
      allele 2 (wild-type). Fam (6-carboxy-fluorescein) is covalently linked to the 5'
      end of the probe for detection of allele 1 (mutant). Each of the reporters is
      quenched by Tamra (6-carboxy-N,N,N', N'-tetramethylrhodamine) attached via a
      linker arm located at the 3'-end of each probe. The two probes were complementary
      to a 24-base sequence at the factor V Leiden mutation site, but differing in the
      5'-labelled reporter dye and the nucleotide opposite the mutation site (C vs T).
      Wild-type and factor V Leiden alleles were differentiated in highly purified DNA
      and crudely purified DNA specimens. The assay was successfully applied to genomic
      DNA from leukocytes isolated from whole blood. The factor V status of 120
      patients as determined by this method was in complete concordance with a standard
      PCR-based assay and clearly discriminated between healthy wild-type (+/+), factor
      V Leiden homozygote (-/-) and heterozygote (+/-) carriers.

PMID- 10970730
TI  - Mutation screening of the chromosome 8q24.3-human activity-regulated cytoskeleton
      associated gene (ARC) in idiopathic generalized epilepsy.
AB  - Idiopathic generalized epilepsy (IGE) comprises a heterogeneous group of
      disorders, in which a high genetic predisposition and a complex mode of
      inheritance have been suggested. However, genes, which confer liability to common
      IGE subtypes including juvenile myoclonic epilepsy (JME) and childhood absence
      epilepsy (CAE) have not been identified so far. Here, we tested the hypothesis
      that genetic variation in the human homolog of the <<<<activity-regulated
      cytoskeleton-associated gene>>>> (ARC) contributes to the etiology of common IGE
      disorders. The gene has recently been mapped to chromosome 8q24.3, a region which
      spans previously identified major IGE susceptibility loci. A systematic search
      for mutations was performed in 143 patients with a known family history of IGE.
      However, no evidence for functional variants was found in the ARC coding
      sequence. Nevertheless, we detected a novel common C489T single nucleotide
      polymorphism, which provides a useful marker in genetic linkage and association
      studies. By performing a population- and family-based study we however failed to
      show significant association between this novel single nucleotide polymorphism
      and IGE, a finding, which most likely rules out that genetic variation in or
      close to the ARC gene confers liability to common IGE subtypes.

PMID- 10970731
TI  - Identification and characterization of two new, highly polymorphic loci adjacent
      to GNAS1 on chromosome 20q13.3.
AB  - GNAS1, which is located in the chromosomal region 20q13.3, gives rise to
      maternally, paternally or bi-allelically expressed transcripts including the one
      that encodes the alpha subunit of the stimulatory G protein. Numerous naturally
      occurring mutations of this gene have been identified in several different
      disorders including certain forms of pseudohypoparathyroidism, progressive
      osseous heteroplasia, McCune-Albright syndrome and acromegaly. Polymorphic
      markers currently employed in the genetic evaluation of these disorders
      frequently prove uninformative owing to a low heterozygosity value associated
      with each marker. We searched for potentially polymorphic tandem repeats close to
      the GNAS1 locus, and identified two new, highly polymorphic loci that are located
      within a;48-kb region immediately downstream of this gene. These new
      microsatellite markers, with their high polymorphism information content, may
      prove to be useful in genetic studies related to GNAS1 as well as to other genes
      located in the flanking genomic region.

PMID- 10970732
TI  - Identification of novel common polymorphisms in the promoter region of the TIMP-3
      gene in Czech population.
AB  - We investigated possible polymorphisms in the promoter regions of the TIMP-1, 2
      and 3 genes (tissue inhibitor of metalloproteinases) to establish their
      frequencies in the Caucasian population. Polymorphisms were analysed by means of
      heteroduplex analysis and fragments with altered mobility were sequenced. No
      polymorphisms were found in the promoters for TIMP-1 and 2 but three novel
      polymorphisms (-899T/A, -915A/G and -1296T/C) were identified in the promoter
      region of the TIMP-3. Allele frequencies in a sample of healthy Caucasian
      subjects (n=95) were determined by PCR followed by restriction analyses with
      specific endonucleases. Allele frequencies of the -899A, -915G and -1296C
      polymorphisms were 0.05, 0.39 and 0. 40, respectively. We conclude that the 
      915A/G and -1296T/C variants of the TIMP-3 gene appear to be common polymorphisms
      in the Caucasian Czech population.

PMID- 10970733
TI  - Mass spectral analysis of a protein complex using single-chain antibodies
      selected on a peptide target: applications to functional genomics.
AB  - Genome projects are identifying an ever-increasing number of genes, accelerating
      the need for reagents to study the expression of these genes and elucidate the
      function and cellular location of the gene products. Our goal was to develop a
      strategy to allow human single-chain variable fragment (scFv) antibodies to be
      used for these endeavors. A library containing 7x10(9) individual variants was
      displayed by bacteriophage and selected against a biotinylated peptide
      corresponding to the C-terminal 15 amino acid residues of Ku86, one component of
      a heterodimer involved in double-stranded DNA break repair. Four unique scFv
      antibodies were recovered that not only recognized the selected peptide, but also
      the intact protein. Three of the scFv antibodies were expressed in soluble form
      and recognized Ku86 by Western analysis. The affinity of one of the scFv
      antibodies for Ku86 was 16 nM as measured by BIAcore analysis. scFv
      immunoprecipitation of Ku86 also isolated the other component of the heterodimer,
      Ku70, as determined by Western analysis and mass spectrometry. These results
      demonstrate the utility of scFv antibodies as invaluable reagents for functional
      genomics.

PMID- 10970734
TI  - Structures of thermolabile mutants of human glutathione transferase P1-1.
AB  - An N-capping box motif (Ser/Thr-Xaa-Xaa-Asp) is strictly conserved at the
      beginning of helix alpha6 in the core of virtually all glutathione transferases
      (GST) and GST-related proteins. It has been demonstrated that this local motif is
      important in determining the alpha-helical propensity of the isolated alpha6
      peptide and plays a crucial role in the folding and stability of GSTs. Its
      removal by site-directed mutagenesis generated temperature-sensitive folding
      mutants unable to refold at physiological temperature (37 degrees C). In the
      present work, variants of human GSTP1-1 (S150A and D153A), in which the capping
      residues have been substituted by alanine, have been generated and purified for
      structural analysis. Thus, for the first time, temperature-sensitive folding
      mutants of an enzyme, expressed at a permissive temperature, have been
      crystallized and their three-dimensional structures determined by X-ray
      crystallography. The crystal structures of human pi class GST temperature
      sensitive mutants provide a basis for understanding the structural origin of the
      dramatic effects observed on the overall stability of the enzyme at higher
      temperatures upon single substitution of a capping residue.

PMID- 10970735
TI  - A dynamic model for the allosteric mechanism of GroEL.
AB  - GroEL-assisted protein folding is regulated by a cycle of large coordinated
      domain movements in the 14-subunit double-ring assembly. The transition path
      between the closed (unliganded) and the open (liganded) states, calculated with a
      targeted molecular dynamics simulation, shows the highly complex subunit
      displacements required for the allosteric transition. The early downward motion
      of the small intermediate domain induced by nucleotide binding emerges as the
      trigger for the larger movements of the apical and equatorial domains. The
      combined twisting and upward displacement of the apical domain determined for a
      single subunit is accommodated easily in the heptamer ring only if its opening is
      concerted. This is a major source of cooperative ligand binding within a ring. It
      suggests also that GroEL has evolved so that the motion required for heptamer
      cooperativity is encoded in the individual subunits. A calculated model for a di
      cis 14-subunit assembly is found to be destabilized by strong steric repulsion
      between the equatorial domains of the two rings, the source of negative
      cooperativity. The simulation results, which indicate that transient interactions
      along the transition path are essential for GroEL function, provide a detailed
      structural description of the motions that are involved in the GroEL allosteric
      cycle.

PMID- 10970736
TI  - Differential remodeling of the HIV-1 nucleosome upon transcription activators and
      SWI/SNF complex binding.
AB  - Here we have examined HIV-1 nucleosome remodeling upon the binding of
      transcription factors and the SWI/SNF complex using a novel approach. The
      approach combines UV laser protein-DNA crosslinking, electrophoretic mobility
      shift analysis and DNase I protection analysis with immunochemical techniques. It
      was found that single activator-bound HIV-1 nucleosomes exhibit very weak
      perturbation in histone NH(2) tail-DNA interactions. However, the simultaneous
      binding of the transcription activators Sp1, NF-kB1, LEF-1 and USF
      synergistically increased the release of histone NH(2) tails from nucleosomal
      DNA. In contrast, the binding of SWI/SNF complex to HIV-1 nucleosome disrupted
      structured histone domain-DNA contacts, but not histone NH(2) tail-DNA
      interactions. Stable remodeled nucleosomes, (obtained after detachment of
      SWI/SNF), displayed identical structural alterations with those bound to SWI/SNF.
      These results demonstrate a different in vitro remodeling of the HIV-1 nucleosome
      upon the binding of multiple transcription activators and of SWI/SNF complex.

PMID- 10970737
TI  - Analysis of yeast MSH2-MSH6 suggests that the initiation of mismatch repair can
      be separated into discrete steps.
AB  - The yeast MSH2-MSH6 complex is required to repair both base-pair and single base
      insertion/deletion mismatches. MSH2-MSH6 binds to mismatch substrates and
      displays an ATPase activity that is modulated by mispairs that are repaired in
      vivo. To understand early steps in mismatch repair, we analyzed mismatch repair
      (MMR) defective MSH2-msh6-F337A and MSH2-msh6-340 complexes that contained amino
      acid substitutions in the MSH6 mismatch recognition domain. While both
      heterodimers were defective in forming stable complexes with mismatch substrates,
      only MSH2-msh6-340 bound to homoduplex DNA with an affinity that was similar to
      that observed for MSH2-MSH6. Additional analyses suggested that stable binding to
      a mispair is not sufficient to initiate recruitment of downstream repair factors.
      Previously, we observed that MSH2-MSH6 forms a stable complex with a palindromic
      insertion mismatch that escapes correction by MMR in vivo. Here we show that this
      binding is not accompanied by either a modulation in MSH2-MSH6 ATPase activity or
      an ATP-dependent recruitment of the MLH1-PMS1 complex. Together, these
      observations suggest that early stages in MMR can be divided into distinct
      recognition, stable binding, and downstream factor recruitment steps.

PMID- 10970738
TI  - A chemical phylogeny of group I introns based upon interference mapping of a
      bacterial ribozyme.
AB  - Despite its small size, the 205 nt group I intron from Azoarcus tRNA(Ile) is an
      exceptionally stable self-splicing RNA. This IC3 class intron retains the
      conserved secondary structural elements common to group I ribozymes, but lacks
      several peripheral helices. These features make it an ideal system to establish
      the conserved chemical basis of group I intron activity. We collected nucleotide
      analog interference mapping (NAIM) data of the Azoarcus intron using 14 analogs
      that modified the phosphate backbone, the ribose sugar, or the purine base
      functional groups. In conjunction with a complete interference set collected on
      the Tetrahymena group I intron (IC1 class), these data define a "chemical
      phylogeny" of functional groups that are important for the activity of both
      introns and that may be common chemical features of group I intron catalysts. The
      data identify the functional moieties most likely to play a conserved role as
      ligands for catalytic metal ions, the substrate helix, and the guanosine
      cofactor. These include backbone functional groups whose nucleotide identity is
      not conserved, and hence are difficult to identify by standard phylogenetic
      sequence comparisons. The data suggest that both introns utilize an equivalent
      set of long range tertiary interactions for 5'-splice site selection between the
      P1 substrate helix and its receptor in the J4/5 asymmetric bulge, as well as an
      equivalent set of 2'-OH groups for P1 helix docking into most of the single
      stranded segment J8/7. However, the Azoarcus intron appears to make an
      alternative set of interactions at the base of the P1 helix and at the 5'-end of
      the J8/7. Extensive differences were observed within the intron peripheral
      domains, particularly in P2 and P8 where the Azoarcus data strongly support the
      proposed formation of a tetraloop-tetraloop receptor interaction. This chemical
      phylogeny for group I intron catalysis helps to refine structural models of the
      RNA active site and identifies functional groups that should be carefully
      investigated for their role in transition state stabilization.

PMID- 10970739
TI  - Identification of ENV determinants in V3 that influence the molecular anatomy of
      CCR5 utilization.
AB  - The V3 loop of the ENV glycoprotein exerts a dominant influence on the
      interaction of gp120 with coreceptors. Primary env genes cloned from sequential
      isolates from two seroconverters revealed Pro-->Ala conversion in the conserved
      GPG motif of the V3 crown in seven of 17 R5 ENV. ENV containing the GPG motif in
      the V3 crown had fusogenic activity with chimeric receptors containing either the
      N terminus or loops of CCR5, whereas those with the GAG variant utilized only the
      former. Site-directed mutagenesis of multiple primary and prototypic R5 env genes
      demonstrated that the GPG motif was necessary for dual utilization of the N
      terminus and body of CCR5 in both gain and loss-of-function experiments. All ENV
      containing the GPG V3 crown showed CCR5 binding in the presence of soluble CD4,
      whereas it was not detected with the GAG variants. Molecular dynamic simulations
      of a V3 peptide predicts that the Pro-->Ala substitution results in a
      conformational change with loss of the crown structure. These studies demonstrate
      that sequences in the third hypervariable region determine the specificity of
      coreceptor utilization for fusion, and that a conserved motif in the crown
      directly influences the molecular anatomy of the interaction between gp120 and
      CCR5.

PMID- 10970740
TI  - Accomodation of S-cis-tamoxifen-N(2)-guanine adduct within a bent and widened DNA
      minor groove.
AB  - The non-steroidal anti-estrogen tamoxifen [TAM] has been in clinical use over the
      last two decades as a potent adjunct chemotherapeutic agent for treatment of
      breast cancer. It has also been given prophylactically to women with a strong
      family history of breast cancer. However, tamoxifen treatment has also been
      associated with increased endometrial cancer, possibly resulting from the
      reaction of metabolically activated tamoxifen derivatives with cellular DNA. Such
      DNA adducts can be mutagenic and the activities of isomeric adducts may be
      conformation-dependent. We therefore investigated the high resolution NMR
      solution conformation of one covalent adduct (cis-isomer, S-epimer of [TAM]G)
      formed from the reaction of tamoxifen [TAM] to N(2)-of guanine in the d(C-[TAM]G
      C).d(G-C-G) sequence context at the 11-mer oligonucleotide duplex level. Our NMR
      results establish that the S-cis [TAM]G lesion is accomodated within a widened
      minor groove without disruption of the Watson-Crick [TAM]G. C and flanking Watson
      Crick G.C base-pairs. The helix axis of the bound DNA oligomer is bent by about
      30 degrees and is directed away from the minor groove adduct site. The presence
      of such a bulky [TAM]G adduct with components of the TAM residue on both the 5'-
      and the 3'-side of the modified base could compromise the fidelity of the minor
      groove polymerase scanning machinery.

PMID- 10970741
TI  - Contribution of cation-pi interactions to the stability of protein-DNA complexes.
AB  - Cation-pi interactions between an aromatic ring and a positive charge located
      above it have proven to be important in protein structures and biomolecule
      associations. Here, the role of these interactions at the interface of protein
      DNA complexes is investigated, by means of ab initio quantum mechanics energy
      calculations and X-ray structure analyses. Ab initio energy calculations indicate
      that Na ions and DNA bases can form stable cation-pi complexes, whose binding
      strength strongly depends on the type of base, on the position of the Na ion, and
      whether the base is isolated or included in a double-stranded B-DNA. A survey of
      protein-DNA complex structures using appropriate geometrical criteria revealed
      cation-pi interactions in 71% of the complexes. More than half of the cation-pi
      pairs involve arginine residues, about one-third asparagine or glutamine residues
      that only carry a partial charge, and one-seventh lysine residues. The most
      frequently observed pair, which is also the most stable as monitored by ab initio
      energy calculations, is arginine- guanine. Arginine-adenine interactions are also
      favorable in general, although to a lesser extent, whereas those with thymine and
      cytosine are not. Our calculations show that the major contribution to cation-pi
      interactions with DNA bases is of electrostatic nature. These interactions often
      occur concomitantly with hydrogen bonds with adjacent bases; their strength is
      estimated to be from three to four times lower than that of hydrogen bonds.
      Finally, the role of cation-pi interactions in the stability and specificity of
      protein-DNA complexes is discussed.

PMID- 10970742
TI  - Mutational analysis of Escherichia coli PepA, a multifunctional DNA-binding
      aminopeptidase.
AB  - Escherichia coli PepA is a hexameric aminopeptidase that is also endowed with a
      DNA-binding activity that functions in transcription control and plasmid dimer
      resolution. To gain further insight into the functioning of PepA, mutants were
      selected on the basis of reduced repressibility of a genomic carA-lacZ fusion and
      studied for the various cellular processes requiring PepA, i.e. repression of the
      carAB operon, autoregulation, resolution of ColE1 multimers, and peptide
      proteolysis. The methylation status of the carAB control region was analysed in
      several pepA mutants and purified proteins were assayed in vitro for car operator
      DNA binding. This study provides a critical test of predictions advanced on the
      basis of the structural analysis of PepA and demonstrates the importance for DNA
      binding of several secondary structural elements in the N-terminal domain and
      near the very C terminus. By analysis of single amino acid substitutions, we
      could distinguish the mode of PepA action in car regulation from its action in
      plasmid resolution. We demonstrate that mere binding of PepA to the car control
      region is not sufficient to explain its role in pyrimidine-specific regulation;
      protein-protein interactions appear to play an important role in transcriptional
      repression. The multifunctional character of PepA and of an increasing number of
      transcriptional regulators that combine catalytic and regulatory properties, of
      which several participate in the metabolism of arginine and of the pyrimidines,
      suggests that enzymes and DNA (RNA) binding proteins fulfilling an essential
      primeval function may have been recruited in evolution to fulfil an additional
      regulatory task.

PMID- 10970743
TI  - Structural and functional similarities in the ADP-forming amide bond ligase
      superfamily: implications for a substrate-induced conformational change in
      folylpolyglutamate synthetase.
AB  - Comparison of the three-dimensional structures of folylpolyglutamate synthetase
      (FPGS) and the bacterial cell wall ligase UDP-N-acetylmuramoyl-l-alanine:d
      glutamate ligase (MurD) reveals that these two enzymes have a remarkable
      structural similarity despite a low level of sequence identity. Both enzymes have
      a modular, multi-domain structure and catalyse a similar ATP-dependent reaction
      involving the addition of a glutamate residue to a carboxylate-containing
      substrate, tetrahydrofolate in the case of FPGS, and UDP-N-acetylmuramoyl-l
      alanine in the case of MurD. Site-directed mutations of selected residues in the
      active site of Lactobacillus casei FPGS (P74A, E143A, E143D, E143Q, K185A, D313A,
      H316A, G411A and S412A) showed that most of these changes resulted in an almost
      complete loss of activity. Several of these amino acid residues in FPGS are found
      in structurally equivalent positions to active-site residues in MurD. Some
      insights into the function of these residues in FPGS activity are proposed, based
      on the roles surmised from the structures of two MurD. UDP-N-acetylmuramoyl-l
      alanine.ADP complexes and a MurD. UDP-N-acetylmuramoyl-l-alanine-d-glutamate
      complex. Furthermore, the comparison has led us to propose that conformational
      changes induced by substrate binding in the reaction mechanism of FPGS result in
      a movement of the domains towards each other to more closely resemble the
      orientation of the corresponding domains in MurD. This relative domain movement
      may be a key feature of this new family of ADP-forming amide bond ligases.

PMID- 10970744
TI  - Crystal structures of mouse class II alcohol dehydrogenase reveal determinants of
      substrate specificity and catalytic efficiency.
AB  - The structure of mouse class II alcohol dehydrogenase (ADH2) has been determined
      in a binary complex with the coenzyme NADH and in a ternary complex with both
      NADH and the inhibitor N-cyclohexylformamide to 2.2 A and 2.1 A resolution,
      respectively. The ADH2 dimer is asymmetric in the crystal with different
      orientations of the catalytic domains relative to the coenzyme-binding domains in
      the two subunits, resulting in a slightly different closure of the active-site
      cleft. Both conformations are about half way between the open apo structure and
      the closed holo structure of horse ADH1, thus resembling that of ADH3. The semi
      open conformation and structural differences around the active-site cleft
      contribute to a substantially different substrate-binding pocket architecture as
      compared to other classes of alcohol dehydrogenase, and provide the structural
      basis for recognition and selectivity of alcohols and quinones. The active-site
      cleft is more voluminous than that of ADH1 but not as open and funnel-shaped as
      that of ADH3. The loop with residues 296-301 from the coenzyme-binding domain is
      short, thus opening up the pocket towards the coenzyme. On the opposite side, the
      loop with residues 114-121 stretches out over the inter-domain cleft. A cavity is
      formed below this loop and adds an appendix to the substrate-binding pocket.
      Asp301 is positioned at the entrance of the pocket and may control the binding of
      omega-hydroxy fatty acids, which act as inhibitors rather than substrates. Mouse
      ADH2 is known as an inefficient ADH with a slow hydrogen-transfer step. By
      replacing Pro47 with His, the alcohol dehydrogenase activity is restored. Here,
      the structure of this P47H mutant was determined in complex with NADH to 2.5 A
      resolution. His47 is suitably positioned to act as a catalytic base in the
      deprotonation of the substrate. Moreover, in the more closed subunit, the
      coenzyme is allowed a position closer to the catalytic zinc. This is consistent
      with hydrogen transfer from an alcoholate intermediate where the Pro/His
      replacement focuses on the function of the enzyme.

PMID- 10970745
TI  - Cryo-electron crystallography of two sub-complexes of bovine complex I reveals
      the relationship between the membrane and peripheral arms.
AB  - NADH:ubiquinone oxidoreductase (complex I) is the first and largest enzyme of the
      mitochondrial respiratory chain. The low-resolution structure of the complex is
      known from electron microscopy studies. The general shape of the complex is in
      the form of an L, with one arm in the membrane and the other peripheral. We have
      purified complex I from beef heart mitochondria and reconstituted the enzyme into
      lipid bilayers. Under different conditions, several two-dimensional crystal forms
      were obtained. Crystals belonging to space groups p222(1) and c12 (unit cell 488
      Ax79 A) were obtained at 22 degrees C and contained only the membrane fragment of
      complex I similar to hydrophobic subcomplex Ibeta but lacking the ND5 subunit. A
      crystal form with larger unit cell (534 Ax81 A, space group c12) produced at 4
      degrees C contained both the peripheral and membrane arms of the enzyme, except
      that ND5 was missing. Projection maps from frozen hydrated samples were
      calculated for all crystal forms. By comparing two different c12 crystal forms,
      extra electron density in the projection map of large crystal form was assigned
      to the peripheral arm of the enzyme. One of the features of the map is a deep,
      channel-like, cleft next to peripheral arm. Comparison with available structures
      of the intact enzyme indicates that large hydrophobic subunit ND5 is situated at
      the distal end of the membrane domain. Possible locations of subunit ND4 and of
      other subunits in the membrane domain are proposed. Implications of our findings
      for the mechanism of proton pumping by complex I are discussed.

PMID- 10970746
TI  - Functional and crystallographic characterization of Salmonella typhimurium Cu,Zn
      superoxide dismutase coded by the sodCI virulence gene.
AB  - The functional and three-dimensional structural features of Cu,Zn superoxide
      dismutase coded by the Salmonella typhimurium sodCI gene, have been
      characterized. Measurements of the catalytic rate indicate that this enzyme is
      the most efficient superoxide dismutase analyzed so far, a feature that may be
      related to the exclusive association of the sodCI gene with the most pathogenic
      Salmonella serotypes. The enzyme active-site copper ion is highly accessible to
      external probes, as indicated by quenching of the water proton relaxation rate
      upon addition of iodide. The shape of the electron paramagnetic resonance
      spectrum is dependent on the frozen or liquid state of the enzyme solution,
      suggesting relative flexibility of the copper ion environment. The crystal
      structure (R-factor 22.6%, at 2.3 A resolution) indicates that the dimeric enzyme
      adopts the quaternary assembly typical of prokaryotic Cu,Zn superoxide
      dismutases. However, when compared to the structures of the homologous enzymes
      from Photobacterium leiognathi and Actinobacillus pleuropneumoniae, the subunit
      interface of Salmonella Cu,Zn superoxide dismutase shows substitution of 11 out
      of 19 interface residues. As a consequence, the network of structural water
      molecules that fill the dimer interface cavity is structured differently from the
      other dimeric bacterial enzymes. The crystallographic and functional
      characterization of this Salmonella Cu,Zn superoxide dismutase indicates that
      structural variability and catalytic efficiency are higher in prokaryotic than in
      the eukaryotic homologous enzymes.

PMID- 10970747
TI  - The slow folding reaction of barstar: the core tryptophan region attains tight
      packing before substantial secondary and tertiary structure formation and final
      compaction of the polypeptide chain.
AB  - The slow folding of a single tryptophan-containing mutant of barstar has been
      studied in the presence of 2 M urea at 10 degrees C, using steady state and time
      resolved fluorescence methods and far and near-UV CD measurements. The protein
      folds in two major phases: a fast phase, which is lost in the dead time of
      measurement during which the polypeptide collapses to a compact form, is followed
      by a slow observable phase. During the fast phase, the rotational correlation
      time of Trp53 increases from 2.2 ns to 7.2 ns, and its mean fluorescence lifetime
      increases from 2.3 ns to 3.4 ns. The fractional changes in steady-state
      fluorescence, far-UV CD, and near-UV CD signals, which are associated with the
      fast phase are, respectively, 36 %, 46 %, and 16 %. The product of the fast phase
      can bind the hydrophobic dye ANS. These observations together suggest that the
      folding intermediate accumulated at the end of the fast phase has: (a) about 20 %
      of the native-state secondary structure, (b) marginally formed or disordered
      tertiary structure, (c) a water-intruded and mobile protein interior; and (d)
      solvent-accessible patches of hydrophobic groups. Measurements of the anisotropy
      decay of Trp53 suggest that it undergoes two types of rotational motion in the
      intermediate: (i) fast (tau(r) approximately 1 ns) local motion of its indole
      side-chain, and (ii) a slower (tau(r) approximately 7.2 ns) motion corresponding
      to global tumbling of the entire protein molecule. The ability of the Trp53 side
      chain to undergo fast local motion in the intermediate, but not in the fully
      folded protein where it is completely buried in the hydrophobic core, suggests
      that the core of the intermediate is still poorly packed. The global tumbling
      time of the fully folded protein is faster at 5.6 ns, suggesting that the volume
      of the intermediate is 25 % more than that of the fully folded protein. The rate
      of folding of this intermediate to the native state, measured by steady-state
      fluorescence, far-UV CD, and near-UV CD, is 0.07(+/-0.01) min(-1) This rate
      compares to a rate of folding of 0.03(+/-0.005) min(-1), determined by double
      jump experiments which monitor directly formation of native protein; and to a
      rate of folding of 0.05 min(-1), when determined from time-resolved anisotropy
      measurements of the long rotational correlation time, which relaxes from an
      initial value of 7.2 ns to a final value of 5. 6 ns as the protein folds. On the
      other hand, the amplitude of the short correlation time decreases rapidly with a
      rate of 0.24(+/-0.06) min(-1). These results suggest that tight packing of
      residues in the hydrophobic core occurs relatively early during the observable
      slow folding reaction, before substantial secondary and tertiary structure
      formation and before final compaction of the protein.

PMID- 10970748
TI  - Analysis of the interactions of human ribonuclease inhibitor with angiogenin and
      ribonuclease A by mutagenesis: importance of inhibitor residues inside versus
      outside the C-terminal "hot spot".
AB  - Ribonuclease inhibitor (RI) binds diverse mammalian RNases with extraordinary
      avidity. Here, we have investigated the structural basis for this tight binding
      and broad specificity by mutational analysis of the complexes of RI with
      angiogenin (Ang) and RNase A (K(D)=0.5 fM and 43 fM, respectively). Both crystal
      structures are known; the interfaces are large, and the ligands dock similarly,
      although few of the specific interactions formed are analogous. Our previous
      mutagenesis studies focused primarily on one contact region, containing RI 434
      438 and the enzymatic active site. Many single-residue replacements produced
      extensive losses of binding energy (2.3-5.9 kcal/mol), suggesting that this
      region constitutes a "hot spot" in both cases. We have now explored the roles of
      most of the remaining RI residues that interact with Ang and/or RNase A. One
      major cluster in each complex lies in a Trp-rich area of RI, containing Trp261,
      Trp263, Trp318, and Trp375. Although the energy losses from individual
      replacements in this portion of the Ang complex were small-to-moderate (0-1.5
      kcal/mol), the changes from multiple substitutions were much greater than
      additive, and the binding energy provided by this region is estimated to be
      approximately 6 kcal/mol (30 % of total). Effects of replacing combinations of
      hot spot components had also been found to be superadditive, and this negative
      cooperativity is now shown to extend to the neighboring contact residue RI
      Ser460. The overall contribution of the hot spot, taking superadditivity into
      account, is then approximately 14-15 kcal/mol. The hot spot and Trp-rich regions,
      although spatially well separated, are themselves functionally linked. No other
      parts of the RI-Ang interface appear to be energetically important. Binding of
      RNase A is more sensitive to substitutions throughout the interface, with free
      energy losses>/=1 kcal/mol produced by nearly all replacements examined, so that
      the sum of losses greatly exceeds the binding energy of the complex. This
      discrepancy can be explained, in part, by positive cooperativity, as evident from
      the subadditive effects observed when combinations of residues in either the hot
      spot or Trp-rich region are replaced. These findings suggest that the binding
      energy may be more widely distributed in the RNase A complex than in the Ang
      complex.

PMID- 10970749
TI  - Episiotomy rates: further research required?

PMID- 10970751
TI  - Midwife-led maternity services and consumer 'choice' in an Australian
      metropolitan region.
AB  - OBJECTIVE: Identify the factors determining women's support for midwife-led
      maternity care in an Australian metropolitan region, and identify the
      implications for the role of midwives and for the expansion of options for
      childbearing women. DESIGN: A two-stage research design was utilised. In the
      first stage a sample of women were surveyed regarding their choice of maternity
      service provider and site of provision of maternity services. In the second
      stage, in-depth interviews were used to collect the birthing narratives of a
      sample of 50 women involved in the first stage of the research. SETTING: A
      metropolitan region of Adelaide, South Australia. PARTICIPANTS: Women who had
      given birth to a live baby in the 1991 calendar year, who lived within a
      designated region and who gave birth at one of four hospitals in or near the
      region. In the first stage of the study, 519 women returned surveys, giving a
      response rate of 61.7%. Sixty-four per cent of these women expressed an interest
      in being involved in further research, and fifty of these were randomly selected
      for interview. FINDINGS: Despite recent calls in Australia to increase the
      choices available to childbearing women, these choices are limited by, amongst
      other things, insufficient information about midwife-led maternity services. The
      work of midwives remains silenced and invisible to many women pregnant for the
      first time, who have little idea about what midwives can do. This research shows
      that women's main source of information about midwife care is developed through
      the actual experience of it, particularly in giving birth. This experience leads
      to an extremely positive recognition and appraisal of the work of midwives, such
      that the majority of women indicate that they would be happy with midwife care
      for subsequent births. First-time mothers are significantly disadvantaged in
      terms of choices available to them because of this lack of information about
      midwife-led maternity care. IMPLICATIONS: In the interests of providing
      childbearing women with real choices for maternity care, strategic interventions
      to better publicise the role of midwives and of midwife-led services are needed.

PMID- 10970750
TI  - The hour of birth: comparisons of circadian pattern between women cared for by
      midwives and obstetricians.
AB  - OBJECTIVE: To examine the difference, if any, between midwives' care and
      obstetricians' care in the circadian pattern of the hour of birth in spontaneous
      labour and delivery. DESIGN: A descriptive study comparing the circadian pattern
      of the hour of birth between women cared for by a midwife or an obstetrician.
      SETTING: Data were derived from the Perinatal Database of the Netherlands (LVR),
      comprising 83% of all births under midwives' care and 75% of all births under
      obstetricians' care. SUBJECTS: 57,871 women receiving midwives' care and 31,999
      women receiving obstetricians' care with spontaneous labour and spontaneous
      delivery. MAIN OUTCOME MEASURES: Differences in the circadian rhythms between
      women receiving midwives' care and obstetricians' care. FINDINGS: There was a
      difference in the circadian pattern of the hour of birth between midwives' and
      obstetricians' care. Peak times differed 5.43 hours (CI 4.23-7.03) for
      primiparous and 3.34 hours (CI 3.00-4.08) for multiparous women between the
      midwives' group and the obstetricians' group. CONCLUSION: This study demonstrates
      a remarkable difference in circadian pattern of the hour of birth between
      midwives' care and obstetricians' care. In obstetricians' care the duration of
      normal labour appears to be prolonged, presumably by an increased level of
      stress. In normal birth the care of midwives is preferable.

PMID- 10970752
TI  - Continuity of carer: what matters to women? A review of the evidence.
AB  - OBJECTIVES: To consider how 'continuity of carer' has been defined in the
      literature and to review the literature on what aspects of continuity matter to
      women. DESIGN: Structured literature review. SETTING: The first objective was
      addressed within the context of a review of the organisation of midwifery
      services in the UK; for the second objective a wider literature was drawn on.
      MEASUREMENTS AND FINDINGS: Data were systematically extracted from the identified
      'core' studies on the methods used for assessing continuity of carer and on
      women's satisfaction with periods of care. Continuity of carer was found to be
      defined in these studies as fewer caregivers, either overall or during pregnancy,
      or as a known caregiver in labour. Little attention was paid to other possible
      interpretations of continuity of carer. The literature on what is important to
      women was found to have used four distinct methods and findings were consistent
      within methods. Studies comparing women who had and had not had a known carer in
      labour found no significant differences in satisfaction; those using rankings or
      ratings found that a known intrapartum carer was a relatively low priority and
      most of those using open-ended questions found that few women mentioned
      continuity. In contrast, all studies which asked postnatal women whether a known
      intrapartum carer was important reported that those who had experienced it said
      'yes', while those who had not, generally thought it unimportant. KEY
      CONCLUSIONS: There has been an emphasis in existing literature on continuity of
      carer but little attempt to assess continuity or quality of care. Limited
      definitions of continuity of carer have been used. There is no evidence that
      women who were cared for in labour by a midwife that they had already met were
      more satisfied than those who were not. Other aspects of woman-centred care were
      likely to be more important. Women wanted consistent care from caregivers that
      they trust, but most did not value continuity of carer for its own sake.
      IMPLICATIONS FOR PRACTICE: Limited definitions of continuity of carer seem to be
      becoming ends in themselves. This has particularly been the case with defining
      continuity as 'having a known carer in labour'. The available evidence does not
      justify prioritising this definition of continuity--rather the reverse. This is
      important for both women and midwives since it opens up other possibilities for
      organising services that put less strain on midwives' lives and may be equally
      satisfying for both women and midwives.

PMID- 10970753
TI  - An evaluation of skills acquisition on the WHO/UNICEF Breastfeeding Management
      Course using the pre-validated Breastfeeding Support Skills Tool (BeSST).
AB  - OBJECTIVE: To test the hypothesis that midwives who had completed the 20-hour
      WHO/UNICEF Breastfeeding Management Course would score significantly higher on a
      validated, quantitative measure of breast-feeding support skills, the
      Breastfeeding Support Skills Tool (BeSST), than a control group of midwives who
      had not undertaken the course. DESIGN: Breast feeding support skills were
      assessed using a between-subjects design conducted in midwives who had not
      attended the course and at two weeks following the 20 hour course. PARTICIPANTS
      AND SETTING: Two groups, consisting of 13 pre- and 15 post-course midwives, were
      compared. The research was carried out at four hospital sites in the UK, three of
      which had undertaken the 20 hour course and one which had not adopted the course.
      FINDINGS: Scores on the BeSST were significantly higher in the post-course group
      (mean = 29.9) than in the pre-course group (mean = 19.8), t (23.39) = 2.94, P <
      0.01. KEY CONCLUSIONS: It is clear that breast-feeding support skills, as
      demonstrated by the BeSST, are significantly improved two weeks following the 20
      hour WHO/UNICEF Breastfeeding Management Course. IMPLICATIONS FOR PRACTICE: By
      demonstrating the effectiveness of the 20-hour course in teaching breast-feeding
      support skills, additional hospitals may be encouraged to adopt the course and
      thereby contribute further to the advancement of optimum breast-feeding
      practices. Furthermore, this approach to assessment may be transferred to other
      areas of midwifery practice enabling the effective evaluation of courses and
      assessment of student learning.

PMID- 10970754
TI  - Women's choice? The impact of private health insurance on episiotomy rates in
      Australian hospitals.
AB  - OBJECTIVE: To assess the extent to which variations in episiotomy rates in
      Australian hospitals are justified by clinical variables and to further explore
      the relationships between episiotomy, insurance status, perineal trauma and
      outcomes for babies. DESIGN: A retrospective analysis of anonymous medical record
      data using logistic regression models, aimed at identifying factors influencing
      both episiotomy rates and outcomes for babies. SETTING: A large regional public
      hospital, New South Wales, Australia. PARTICIPANTS: The study sample consisted of
      2028 women who delivered vaginally during a 12 month period during 1996-1997.
      RESULTS: After controlling for clinical and other factors privately insured women
      were estimated to be up to twice as likely to experience episiotomy as publicly
      insured women. This difference most plausibly reflects differences in labour
      management styles between obstetricians and midwives. Other significant
      contributors to episiotomy were instrumental delivery, indications of possible
      fetal distress and lower parity. Severe perineal trauma (third degree tear) was
      found to be positively associated with episiotomy. Furthermore, the incidence of
      additional tears requiring suture was also substantially higher among privately
      insured women, the net effect being that these women had a substantially lower
      chance of achieving an intact perineum. Neither episiotomy nor insurance status
      had any significant effect on the well-being of babies. IMPLICATIONS FOR
      PRACTICE: Private health insurance appears to deny many women the opportunity of
      achieving normal vaginal delivery with intact perineum. Episiotomy rates amongst
      privately insured women in Australia may be higher than is clinically
      appropriate, and severe perineal trauma within this study was associated with
      this practice.

PMID- 10970755
TI  - Action research to improve the pre-registration midwifery curriculum--Part I: An
      appropriate methodology.
AB  - OBJECTIVE: To improve the pre-registration midwifery curriculum locally and
      influence national policy and guidelines for these programmes. DESIGN: Action
      research provided the framework for the study where a multi-method approach was
      largely qualitative to attempt to capture the context and complexity in which the
      midwifery programme operates. The study comprises a synthesis of two separate but
      interwoven research projects: a national study about the effectiveness of
      midwifery education (the EME project) and an evaluation and re-design of the
      three year pre-registration midwifery programme in a large multi-sited university
      in England. SETTING: A large university in England. PARTICIPANTS: The EME project
      39 case study students, their teachers, practice-based mentors/assessors,
      preceptors and supervisors of midwives or managers; 50 students from the local
      university's midwifery programme, their teachers and practice-based
      mentors/assessors from six sites; 41 women who gave birth to their babies in a
      large teaching hospital in the East Midlands; and a professional network of
      experienced midwives whose role is to advise the statutory body regulating
      midwifery programmes in England. FINDINGS: Overall the three-year, pre
      registration route into midwifery was found to be an effective preparation for
      contemporary midwifery practice as judged against a model of a competent midwife
      at the point of registration. However, there was evidence to suggest that not all
      students are equipped to practise competently and confidently in contexts of
      uncertainty and change in the National Health Service. Factors which emerged as
      influencing curriculum effectiveness related to: recruitment and selection;
      curriculum structure, appropriateness; and robustness of assessment schemes; the
      preparation of and support for assessors; and the role of the midwife teacher in
      assessment in practice settings. CONCLUSION AND IMPLICATIONS FOR PRACTICE:
      Diagnosing problems and initiating actions as a collaborative process formed an
      important part of designing and implementing an 'ideal' curriculum in constrained
      health and higher education contexts. The need for on-going dialogue, critical
      reflection, and research to facilitate and assess learning more effectively in
      the 'caring' professions emerged as necessary to ensure that only competent
      practitioners have a license to practise.

PMID- 10970756
TI  - What do we know about herbal morning sickness treatments? A literature survey.
AB  - OBJECTIVE: A literature survey investigating the use of herbs to treat morning
      sickness, with particular reference to what is known about their safety. DESIGN:
      All major English language medical, nursing and scientific databases as well as
      300 World Wide Web sites, Internet newsgroups, books and magazines were searched
      for information about the use and safety of herbs in pregnancy. FINDINGS: A
      search of medical databases failed to locate any articles which specifically
      reported investigations of the safety of herbs used during pregnancy. Of 300 non
      medical sources studied 75 cited the use of herbs in pregnancy. The most commonly
      cited herbs for morning sickness were ginger, chamomile, peppermint and raspberry
      leaf (55, 37, 44 and 63% cited respectively). There was no consensus in the
      popular literature about whether or not each of these herbs was safe for use in
      pregnancy. Seven sources (6%) cited chamomile and peppermint as unsafe, while 16
      (12%) cited the use of ginger and 11 (15%) the use of raspberry leaf as unsafe
      during pregnancy. CONCLUSIONS: Herbal remedies are often seen as safe, 'drug
      free' treatments for morning sickness. However, the contradictory information and
      dearth of original research related to their safety indicates that these
      compounds should be used with caution.

PMID- 10970757
TI  - Developing high-quality research in midwifery: lessons learned from the midwifery
      research database, MIRIAD.
AB  - BACKGROUND: Research in midwifery is a relatively new development in many
      countries, and as a consequence it can be difficult to identify ongoing and
      completed research, to network with other researchers in similar fields, and to
      plan appropriately to develop research and research capacity. This paper
      describes the establishment of the UK Midwifery Research Database, MIRIAD, which
      aimed to address these problems. METHOD: Funding from the Department of Health
      (England) supported the establishment of MIRIAD in 1988. Systems and procedures
      were set in place to collect, store, analyse and disseminate information about
      ongoing and completed research in midwifery. Six detailed reports were published.
      MIRIAD was closed in 1999 as a result of lack of ongoing funding. KEY FINDINGS:
      466 studies were registered with MIRIAD, with start dates ranging from 1974 to
      1998. The majority of studies examined clinical topics. A wide range of research
      approaches were used. Studies were supported by a range of sources, including
      employers and national funding agencies. There were many examples of high
      quality, peer-reviewed, and externally funded studies which can be used to inform
      practice. Issues raised by some studies, however, included concerns about
      research quality, inadequacy of some supervision, low rate of publication, and
      inconsistency in gaining ethics committee approval. CONCLUSIONS: Research in
      midwifery in the UK has matured over the past 25 years. It still faces many
      challenges, including the need to maintain quality and to gain more national
      funding support. Lessons have also been learned about the need for quality in
      research information systems. Ongoing assessment of the growth and direction of
      research in midwifery is recommended, possibly through monitoring of the generic
      NHS database, the National Research Register (NRR), to inform strategic
      developments in research and research capacity at national; regional and local
      levels.

PMID- 10970759
TI  - International news.

PMID- 10970758
TI  - Cord-care practice in Scotland.
AB  - OBJECTIVE: To identify the range of policies, practices and rationale for
      umbilical-cord stump care in the NHS in Scotland. DESIGN: A postal questionnaire
      survey completed in two stages. The first stage elicited the views of Heads of
      Midwifery/Senior Midwives, and the second stage the views of midwives, enrolled
      nurses and nursery nurses. SETTING: NHS units in Scotland providing intrapartum
      care. They were separated into large and small units with small units having < or
      = 1000 deliveries per year (n = 178), and large units > 1000 deliveries per year
      (n = 300). PARTICIPANTS: The Heads of Midwifery/Senior Midwives from the 51 units
      were invited to participate in the study and 49 (96.1%) replied. In stage two 512
      maternity unit employees were sent questionnaires and 390 (76.2%) replied. These
      were six enrolled nurses, 20 nursery nurses and 360 midwives and four respondents
      of unspecified occupation. MEASUREMENTS: The existence of cord-care policies and
      their rationale. FINDINGS: About half of the units that responded had a written
      policy. Large units were four times more likely than small units to have a
      written policy. Both managers and staff reported that the most common
      policy/agreed practice was no specific care (cord observed and only cleaned if
      soiled). Where a written policy existed, less than one-half of the Heads of
      Midwifery/Senior Midwives and less than one third of the staff reported that the
      basis for this policy was research. KEY CONCLUSIONS: Units with a written policy
      are in the minority and small units are far less likely to have such a policy.
      Wide variation exists in policy, practice and rationale. Diversity within and
      between units creates anxiety and disillusionment for practitioners. It may also
      cause confusion for patients who are exposed to different cord-care practices
      either as these change over time or because they use different units.
      IMPLICATIONS FOR PRACTICE: The midwifery profession must examine this area of
      practice and determine how to address this lack of evidence. Further research is
      required to determine the most effective method of cord care and how best to put
      the findings into practice. Outstanding questions which beg further investigation
      are: How do cords heal and separate and what bacteria are naturally involved in
      this process? What constitutes an infected cord as opposed to a colonised cord?

PMID- 10970760
TI  - Identification of Mycobacterium avium DNA sequences that encode exported proteins
      by using phoA gene fusions.
AB  - SETTING: Mycobacterium avium is the major cause of disseminated infection in
      patients with late stage AIDS. OBJECTIVE: In order to identify M. avium genes
      that may be involved in bacterial uptake and intracellular survival, a phoA 
      based reporter system was used to identify genes that encoded surface-expressed
      or exported proteins. DESIGN: PhoA (alkaline phosphatase) is only active if the
      protein is exported across the cell membrane into the periplasm. Consequently,
      detectable PhoA activity requires the fusion of a promoterless phoA gene with a
      DNA fragment containing a functional promoter and export leader sequence. A M.
      avium promoter library was constructed in the phoA reporter plasmid pJEM11 and
      screened in M. smegmatis for expression of active PhoA. RESULTS: More than 100
      independent PhoA(+)recombinants were isolated, of which 15 were sequenced. Most
      of these exhibited varying degrees of homology with published M. avium, M.
      tuberculosis, M. bovis and M. leprae sequences. Based on sequence homology, one
      M. avium sequence was identified as a homologue of the M. tuberculosis phosphate
      transport gene phoS2 (Ag88). Another M. avium sequence was homolog with a
      putative M. tuberculosis cutinase gene. Both of these M. avium genes were cloned
      and sequenced. Several other M. avium sequences were homologous with, as yet,
      unidentified M. tuberculosis genes. CONCLUSION: PhoA fusion technology is
      applicable to the study of atypical slow growing mycobacteria. Most of the M.
      avium exported proteins identified in this study are highly homologous with genes
      from M. tuberculosis and M. leprae. In addition, parallels in gene organization
      were identified between M. avium and members of the M. tuberculosis complex.

PMID- 10970761
TI  - Immunologic diagnosis of tuberculosis: a review.
AB  - The diagnosis of tuberculosis (TB) principally rests on the sputum examination
      and culture. However, the sensitivity of sputum smear for acid-fast bacteria is
      only approximately 50% and sputum culture has a relatively long turnaround time.
      As a result, a number of studies have been conducted in an attempt to find a
      rapid and accurate diagnostic test for TB. They include serological assays
      against various mycobacterial antigens. Here we review the merits and
      deficiencies of the serological tests for TB. In general, serological assays have
      a high negative predictive value, making them potentially useful as a screening
      test to rule out active TB although in HIV-positive individuals, low sensitivity
      and low negative predictive value compromises the accuracy of the seroassays in
      this group of individuals. In populations where the prevalence of latent TB
      infection is high, the relatively low positive predictive value of the tests
      reduces their specificity for active TB. Furthermore, the higher costs and
      greater training required in performing these tests makes it important that
      future studies also assess whether their use affects patient outcomes in
      management of TB.

PMID- 10970762
TI  - Characterization of a two-component system, devR-devS, of Mycobacterium
      tuberculosis.
AB  - By subtractive hybridization, we isolated genes, differentially expressed in
      virulent strain (dev), that are expressed at higher levels in the virulent
      Mycobacterium tuberculosis H37Rv strain in comparison to its avirulent
      counterpart, H37Ra, and consequently may be associated with the virulence
      phenotype of M. tuberculosis. A two-component system, devR-devS, was identified
      by DNA sequencing of a dev clone. DevR, the predicted gene product of devR, is a
      response regulator (RR) in the NarL/ UhpA subfamily of two-component systems. The
      devS gene product displayed homology with histidine protein kinases (HPKs)
      including UhpB, NarX and NarQ. The devR-devS locus is preceded by gene Rv3134c
      that encodes a putative alanine-aline- rich protein. This locus was conserved in
      M. tuberculosis and M. bovis BCG but not in other mycobacteria. A devR -lacZ
      transcription fusion demonstrated beta-galactosidase activity in M. smegmatis and
      in M. tuberculosis. The devR and devS genes were cotranscribed and the levels of
      their transcripts were lower in two isolates of the avirulent H37Ra strain in
      comparison to the virulent H37Rv strain of M. tuberculosis. The level of DevR
      protein was also lower in one of the H37Ra strains in comparison to the H37Rv
      strain. However, in a third isolate of H37Ra, RNA and protein expression was
      equivalent to that in the H37Rv strain. Electron microscopic immunogold analysis
      of M. tuberculosis grown in laboratory medium and within human monocytes revealed
      specific labelling for DevR protein within the bacteria and the phagosomal lumen
      of infected monocytes. These findings collectively suggest a potential role for
      devR-devS in the regulation of genetic programmes unique to the tubercle
      bacillus.

PMID- 10970763
TI  - A longitudinal study of in vitro IFNgamma production and cytotoxic T cell
      responses of tuberculosis patients in the gambia.
AB  - SETTING: This study was carried out at the MRC Laboratories, The Gambia.
      OBJECTIVES: To characterize the antigen-specific IFNgamma production and
      cytotoxic T cell (CTL) responses of patients during active tuberculosis,
      treatment, and following recovery. DESIGN: PBMC were isolated from 37 patients
      with tuberculosis and incubated with either PPD, live M. bovis BCG, or no antigen
      and IFNgamma production measured after 7 days. CTL activity against these
      antigens was determined using autologous antigen-pulsed monocyte-derived
      macrophages as target cells. A subset of these patients (7-18 depending on
      antigen and assey used) were tested 2 months into drug treatment and 3 months
      after discharge. A group of blood bank donors (n= 21) were also tested to
      evaluate IFNgamma responses in endemic controls; a subset (n= 16) were also
      tested for CTL activity. RESULTS: The ability to produce IFNgamma in response to
      mycobacterial antigens correlated with the Mantoux skin test status of the
      patient. IFNgamma production to live M. bovis BCG was diminished at diagnosis but
      returned after 2 months of drug treatment, and was sustained after completion of
      drug therapy. The CTL responses to both PPD and live M. bovis BCG were reduced
      during the period of drug treatment compared to those at diagnosis, but returned
      to the original levels after recovery. CONCLUSIONS: Drug treatment induced marked
      alterations in the immune responses of tuberculosis patients with induction of
      IFNgamma production in response to stimulation with live M. bovis BCG. This may
      indicate activation of both CD4 and CD8 T cells.

PMID- 10970764
TI  - Hormone-stimulated calcium release is inhibited by cytoskeleton-disrupting toxins
      in AR4-2J cells.
AB  - We have studied the role of the actin cytoskeleton in bombesin-induced inositol
      1,4,5-trisphosphate (IP(3))-production and Ca(2+)release in the pancreatic acinar
      tumour cell line AR4-2J. Intracellular and extracellular free
      Ca(2+)concentrations were measured in cell suspensions, using Fura-2. Disruption
      of the actin cytoskeleton by pretreatment of the cells with latrunculin B (10
      microM), cytochalasin D (10 microM) or toxin B from Clostridium difficile (20
      ng/ml) for 5-29 h led to inhibition of both, bombesin-stimulated IP(3)-production
      and Ca(2+)release. The toxins had no effect on binding of bombesin to its
      receptor, on Ca(2+)uptake into intracellular stores and on resting Ca(2+)levels.
      Ca(2+)mobilization from intracellular stores, induced by thapsigargin (100 nM) or
      IP(3)(1 microM) was not impaired by latrunculin B. In latrunculin B-pretreated
      cells inhibition of both, bombesin-stimulated IP(3)- production and Ca(2+)release
      was partly suspended in the presence of aluminum fluoride, an activator of G
      proteins. Aluminum fluoride had no effect on basal IP(3)and Ca(2+)levels of
      control and toxin-pretreated cells. We conclude that disruption of the actin
      cytoskeleton impairs coupling of the bombesin receptor to its G-protein,
      resulting in inhibition of phospholipase C-activity with subsequent decreases in
      IP(3)-production and Ca(2+)release.

PMID- 10970765
TI  - The calmodulin multigene family as a unique case of genetic redundancy: multiple
      levels of regulation to provide spatial and temporal control of calmodulin pools?
AB  - Calmodulin (CaM) is a ubiquitous, highly conserved calcium sensor protein
      involved in the regulation of a wide variety of cellular events. In vertebrates,
      an identical CaM protein is encoded by a family of non-allelic genes, raising
      questions concerning the evolutionary pressure responsible for the maintenance of
      this apparently redundant family. Here we review the evidence that the control of
      the spatial and temporal availability of CaM may require multiple regulatory
      levels to ensure the proper localization, maintenance and size of intracellular
      CaM pools. Differential transcription of the CaM genes provides one level of
      regulation to meet tissue-specific, developmental and cell-specific needs for
      altered CaM levels. Post-transcriptional regulation occurs at the level of mRNA
      stability, perhaps dependent on alternative polyadenylation and differences in
      the untranslated sequences of the multiple gene transcripts. Recent evidence
      indicates that trafficking of specific CaM mRNAs may occur to specialized
      cellular locales such as the dendrites of neurons. This could allow local CaM
      synthesis and thereby help generate local pools of CaM. Local CaM activity may be
      further regulated by post-translational mechanisms such as phosphorylation or
      storage of CaM in a 'masked' form. The spatial resolution of CaM activity is
      enhanced by the limited free diffusion of CaM combined with differential affinity
      for and availability of target proteins. Preserving multiple CaM genes with
      divergent noncoding sequences may be necessary in complex organisms to ensure
      that the many CaM-dependent processes occur with the requisite spatial and
      temporal resolution. Transgenic mouse models and studies on mice carrying single
      and double gene 'knockouts' promise to shed further light on the role of
      specificity versus redundancy in the evolutionary maintenance of the vertebrate
      CaM multigene family.

PMID- 10970766
TI  - Cytosolic [Ca(2+)] modulates basal GLUT1 activity and plays a permissive role in
      its activation by metabolic stress and insulin in rat epithelial cells.
AB  - The aim of this work was to investigate the role of cytosolic free calcium
      ([Ca(2+)]c) in the stimulation of GLUT1 by metabolic stress and insulin.
      Chelation of [Ca(2+)]c with bapta, introduced in rat liver epithelial Clone 9
      cells in the acetoxymethyl (AM) form, decreased their basal rate of 2
      deoxyglucose uptake in a dose-dependent fashion. Maximal inhibition at 75 microM
      bapta was by 38 +/- 8% (n = 8). The effect was partially reversed by ionomycin.
      Basal sugar uptake was also decreased by lowering extracellular [Ca(2+)] in
      ionomycin-permeabilized cells. Increasing [Ca(2+)]c over its resting level of 168
      +/- 32 (n = 27) had no affect on sugar uptake. Chelation of [Ca(2+)]c did not
      change the abundance of surface GLUT1 and had no significant effect on the
      affinity of GLUT1 for sugars. In addition, calcium chelation abolished the
      activation of GLUT1 by azide, arsenate, 2,4-dinitrophenol and insulin. However,
      [Ca(2+)]c did not increase in the presence of azide. We conclude that [Ca(2+)]c,
      near or below its resting level, modulates GLUT1 activity over a considerable
      range and plays a permissive role in the activation of the carrier by metabolic
      stress and insulin.

PMID- 10970767
TI  - Mitochondrial Ca(2+)homeostasis in the regulation of apoptotic and necrotic cell
      deaths.
AB  - Using distinct models of apoptosis and necrosis, we have investigated the effect
      of mitochondrial Ca(2+)(Ca(m)) homeostasis in the regulation of cell death in
      neuroblastoma cells as well as cardiac myocytes. The steady state level of
      Ca(m)was determined as the FCCP-releasable Ca(2+). Culturing cells with low
      concentration of extracellular Ca(2+)(Ca(o)) or with EGTA triggered an early
      reduction in both the Ca(m)store and the membrane potential (DeltaPsi(m)). This
      was followed by the detection of cytochrome c release, caspase activation, and
      apoptosis. Inhibitors of the mitochondrial permeability transition pore such as
      cyclosporin A and Bcl-2 blocked the release of Ca(m)and inhibited apoptosis. In
      contrast, mitochondrial Ca(2+)overload resulted in necrotic cell death. Culturing
      cells in the presence of excess Ca(o)led to increased Ca(m)load together with a
      decrease of DeltaPsi(m)that reached maximum at 1 h, with necrosis occurring at 2
      h. While the decline of Ca(m)and DeltaPsi(m)was a coupled reaction for apoptosis,
      this relationship was uncoupled during necrosis. Clonazepam, a relatively
      specific inhibitor of the mitochondrial Na/Ca exchanger, was able to protect the
      cells from necrosis by reducing Ca(m)overload. Importantly, combination of
      clonazepam and cyclosporin showed a cooperative effect in further reducing the
      Ca(m)overload and abolished cell death. The data imply the participation of
      Ca(m)homeostasis in the regulation of apoptosis and necrosis.

PMID- 10970768
TI  - The roles of P(2X1)and P(2T AC)receptors in ADP-evoked calcium signalling in
      human platelets.
AB  - The roles of P(2X1)and P(2T AC)receptors in ADP-evoked Ca(2+)signalling were
      investigated in fura-2-loaded human platelets. Desensitization of the
      P(2X1)receptor with the selective agonist, alphabeta-methylene ATP, reduced the
      integral of the ADP-evoked rise in [Ca(2+)](i)to about 90% of control; a
      reduction equivalent to the integral of the P(2X1)-evoked response alone. After
      elevating cAMP or cGMP levels using prostaglandin E(1)or sodium nitroprusside,
      prior P(2X1)desensitization reduced the integral of the ADP-evoked response to
      about 70% of control. This reduction was greater than the integral of the P(2X1)
      evoked response alone under the same conditions, suggesting rapidly activated
      Ca(2+)entry via the P(2X1)receptor potentiates Ca(2+)responses evoked via the
      phospholipase C-coupled P(2Y1)receptor. The P(2T AC)receptor antagonist, AR
      C69931MX, at a concentration completely inhibiting aggregation, did not
      significantly affect the initial peaks but caused a significant reduction in the
      integrals of the ADP-evoked rises in [Ca(2+)](i)to about 71% or 77% of controls
      in the presence or absence of external Ca(2+)respectively. This suggests that the
      main effect of lowering cAMP levels after inhibition of adenylyl cyclase via P(2T
      AC)receptors may be reduced Ca(2+)removal from the cytosol. These results
      indicate that both the P(2X1)and P(2T AC)receptors play a significant role in ADP
      evoked Ca(2+)signalling in human platelets.

PMID- 10970769
TI  - Nucleoplasmic Ca(2+)loading is regulated by mobilization of perinuclear Ca(2+).
AB  - Regulation of nucleoplasmic calcium (Ca(2+)) concentration may occur by the
      mobilization of perinuclear luminal Ca(2+)pools involving specific Ca(2+)pumps
      and channels of both inner and outer perinuclear membranes. To determine the role
      of perinuclear luminal Ca(2+), we examined freshly cultured 10 day-old embryonic
      chick ventricular cardiomyocytes. We obtained evidence suggesting the existence
      of the molecular machinery required for the bi-directional Ca(2+)fluxes using
      confocal imaging techniques. Embryonic cardiomyocytes were probed with antibodies
      specific for ryanodine-sensitive Ca(2+)channels (RyR2), sarco/endoplasmic
      reticulum Ca(2+)ATPase (SERCA2)-pumps, and fluorescent BODIPY derivatives of
      ryanodine and thapsigargin. Using immunocytochemistry techniques, confocal
      imaging showed the presence of RyR2 Ca(2+)channels and SERCA2-pumps highly
      localized to regions surrounding the nucleus, referable to the nuclear envelope.
      Results obtained from Fluo-3, AM loaded ionomycin-perforated embryonic
      cardiomyocytes demonstrated that gradual increases of extranuclear Ca(2+)from 100
      to 1600 nM Ca(2+)was localized to the nucleus. SERCA2-pump inhibitors
      thapsigargin and cyclopiazonic acid showed a concentration-dependent inhibition
      of nuclear Ca(2+)loading. Furthermore, ryanodine demonstrated a biphasic
      concentration-dependence upon active nuclear Ca(2+)loading. The concomitant
      addition of thapsigargin or cyclopiazonic acid with ryanodine at inhibitory
      concentrations caused an significant increase in nuclear Ca(2+)loading at low
      concentrations of extranuclear added Ca(2+). Our results show that the
      perinuclear lumen in embryonic chick ventricular cardiomyocytes is capable of
      autonomously regulating nucleoplasmic Ca(2+)fluxes.

PMID- 10970770
TI  - Remapping of the RP15 locus for X-linked cone-rod degeneration to Xp11.4-p21.1,
      and identification of a de novo insertion in the RPGR exon ORF15.
AB  - X-linked forms of retinitis pigmentosa (XLRP) are among the most severe, because
      of their early onset, often leading to significant vision loss before the 4th
      decade. Previously, the RP15 locus was assigned to Xp22, by linkage analysis of a
      single pedigree with "X-linked dominant cone-rod degeneration." After clinical
      reevaluation of a female in this pedigree identified her as affected, we remapped
      the disease to a 19.5-cM interval (DXS1219-DXS993) at Xp11.4-p21.1. This new
      interval overlapped both RP3 (RPGR) and COD1. Sequencing of the previously
      published exons of RPGR revealed no mutations, but a de novo insertion was
      detected in the new RPGR exon, ORF15. The identification of an RPGR mutation in a
      family with a severe form of cone and rod degeneration suggests that RPGR
      mutations may encompass a broader phenotypic spectrum than has previously been
      recognized in "typical" retinitis pigmentosa.

PMID- 10970771
TI  - Simple and complex ABCR: genetic predisposition to retinal disease.

PMID- 10970773
TI  - Coupling between inositol 1,4,5-trisphosphate receptors and human transient
      receptor potential channel 1 when intracellular Ca2+ stores are depleted.
AB  - In the present study we have investigated the role of inositol 1,4, 5
      trisphosphate (IP(3)), functional IP(3) receptors (IP(3)Rs) and the human
      homologue of the Drosophila transient receptor potential (Trp) channel, human
      Trp1 (hTrp1), in store-mediated Ca(2+) entry (SMCE) in human platelets.
      Inhibition of IP(3) recycling using Li(+), or the inhibition of IP(3)Rs using
      xestospongin C, both resulted in the inhibition of SMCE activation following
      Ca(2+) store depletion using thapsigargin. Co-immunoprecipitation experiments
      indicated that endogenously expressed hTrp1 couples with IP(3)R type II, but not
      types I or III, in platelets with depleted intracellular Ca(2+) stores, but not
      in control, undepleted cells. These results provide strong evidence for the
      activation of SMCE by conformational coupling involving de novo association
      between IP(3)Rs and a plasma membrane channel in normal human cells.

PMID- 10970774
TI  - Targeting of the zymogen-granule protein syncollin in AR42J and AtT-20 cells.
AB  - Syncollin is a 13-kDa protein associated with the membranes of pancreatic zymogen
      granules. Here we determine the in situ localization of syncollin in pancreatic
      acinar cells from adult and neonatal rats, and study the targeting of green
      fluorescent protein-(GFP-) and His(6)-tagged syncollin chimaeras in model
      exocrine and endocrine secretory cells. Immunocytochemical analysis of the
      distribution of syncollin in fully differentiated and neonatal acinar cells
      revealed a granular pattern that corresponded with that of the zymogen-granule
      markers synaptobrevin 2 and amylase. In fully differentiated acinar cells
      syncollin-positive vesicles were detected in the apical region of the cells,
      whereas in neonatal acinar cells they were found clustered near the cell nucleus.
      Both GFP- and His(6)-tagged syncollin entered the secretory pathway when
      transiently expressed in AR42J or AtT-20 cells. Syncollin-GFP was found
      predominantly in amylase-positive granules in AR42J cells and in
      adrenocorticotrophic hormone- (ACTH-) positive granules in AtT-20 cells.
      Syncollin-GFP was also present in the Golgi complex in AR42J cells. Syncollin
      His(6) became localized in ACTH-containing granules in the neuritic processes of
      AtT-20 cells. In AR42J cells syncollin-His(6) did not co-localize with amylase,
      but was detected in acidic vesicles. These results show that the exocrine protein
      syncollin contains intrinsic cell-type-independent targeting information that is
      retained in both exocrine and endocrine cells after fusion to the GFP tag. In
      contrast, His(6)-tagged syncollin is efficiently targeted to secretory granules
      only in AtT-20 cells and not in AR42J cells.

PMID- 10970772
TI  - Tetrahydrofolate and tetrahydromethanopterin compared: functionally distinct
      carriers in C1 metabolism.
AB  - In most organisms, tetrahydrofolate (H(4)folate) is the carrier of C(1) fragments
      between formyl and methyl oxidation levels. The C(1) fragments are utilized in
      several essential biosynthetic processes. In addition, C(1) flux through
      H(4)folate is utilized for energy metabolism in some groups of anaerobic
      bacteria. In methanogens and several other Archaea, tetrahydromethanopterin
      (H(4)MPT) carries C(1) fragments between formyl and methyl oxidation levels. At
      first sight H(4)MPT appears to resemble H(4)folate at the sites where C(1)
      fragments are carried. However, the two carriers are functionally distinct, as
      discussed in the present review. In energy metabolism, H(4)MPT permits redox-flux
      features that are distinct from the pathway on H(4)folate. In the reductive
      direction, ATP is consumed in the entry of carbon from CO(2) into the H(4)folate
      pathway, but not in entry into the H(4)MPT pathway. In the oxidative direction,
      methyl groups are much more readily oxidized on H(4)MPT than on H(4)folate.
      Moreover, the redox reactions on H(4)MPT are coupled to more negative reductants
      than the pyridine nucleotides which are generally used in the H(4)folate pathway.
      Thermodynamics of the reactions of C(1) reduction via the two carriers differ
      accordingly. A major underlying cause of the thermodynamic differences is in the
      chemical properties of the arylamine nitrogen N(10) on the two carriers. In
      H(4)folate, N(10) is subject to electron withdrawal by the carbonyl group of p
      aminobenzoate, but in H(4)MPT an electron-donating methylene group occurs in the
      corresponding position. It is also proposed that the two structural methyl groups
      of H(4)MPT tune the carrier's thermodynamic properties through an entropic
      contribution. H(4)MPT appears to be unsuited to some of the biosynthetic
      functions of H(4)folate, in particular the transfer of activated formyl groups,
      as in purine biosynthesis. Evidence bearing upon whether H(4)MPT participates in
      thymidylate synthesis is discussed. Findings on the biosynthesis and phylogenetic
      distribution of the two carriers and their evolutionary implications are briefly
      reviewed. Evidence suggests that the biosynthetic pathways to the two carriers
      are largely distinct, suggesting the possibility of (ancient) separate origins
      rather than divergent evolution. It has recently been discovered that some
      eubacteria which gain energy by oxidation of C(1) compounds contain an H(4)MPT
      related carrier, which they are thought to use in energy metabolism, as well as
      H(4)folate, which they are thought to use for biosynthetic reactions.

PMID- 10970775
TI  - Overexpression of antizyme in the hearts of transgenic mice prevents the
      isoprenaline-induced increase in cardiac ornithine decarboxylase activity and
      polyamines, but does not prevent cardiac hypertrophy.
AB  - Two lines of transgenic mice were produced with constitutive expression of
      antizyme-1 in the heart, driven from the cardiac alpha-myosin heavy chain
      promoter. The use of engineered antizyme cDNA in which nucleotide 205 had been
      deleted eliminated the need for polyamine-mediated frameshifting, normally
      necessary for translation of antizyme mRNA, and thus ensured the constitutive
      expression of antizyme. Antizyme-1 is thought to be a major factor in regulating
      cellular polyamine content, acting both to inhibit ornithine decarboxylase (ODC)
      activity and to target it for degradation, as well as preventing polyamine
      uptake. The two transgenic lines had substantial, but different, levels of
      antizyme in the heart, as detected by Western blotting and by the ability of
      heart extracts to inhibit exogenous purified ODC. Despite the high levels of
      antizyme, endogenous ODC activity was not completely abolished, with 10-39%
      remaining, depending on the transgenic line. Additionally, a relatively small
      decrease (30-32%) in cardiac spermidine content was observed, with levels of
      putrescine and spermine unaffected. Interestingly, although the two lines of
      transgenic mice had different antizyme expression levels, they had almost
      identical cardiac polyamine content. When treated with a single acute dose of
      isoprenaline (isoproterenol), cardiac ODC activity and putrescine content were
      substantially increased (by 14-fold and 4.7-fold respectively) in non-transgenic
      littermate mice, but these increases were completely prevented in the transgenic
      mice from both founder lines. Prolonged exposure to isoprenaline also caused
      increases in cardiac ODC activity and polyamine content, as well as an increase
      in cardiac growth, in non-transgenic mice. Although the increases in cardiac ODC
      activity and polyamine content were prevented in the transgenic mice from both
      founder lines, the increase in cardiac growth was unaffected. These transgenic
      mice thus provide a valuable model system in which to study the importance of
      polyamine levels in cardiac growth and electrophysiology in response to stress.

PMID- 10970776
TI  - Peptide YY Y1 receptor activates mitogen-activated protein kinase and
      proliferation in gut epithelial cells via the epidermal growth factor receptor.
AB  - The G-protein-coupled peptide YY (PYY)/neuropeptide Y Y1 receptor (Y1R) subtype
      is highly expressed in the proliferative zone of human colonic crypt epithelial
      cells but biochemical and biological support for growth effects have been
      lacking. Using a model gut epithelial cell system, we have stably expressed the
      human Y1R in IEC-6 cells and show that the Y1R does couple to mitogen-activated
      protein kinase (MAPK) phosphorylation and cell growth. This pathway uses
      pertussis-toxin-sensitive G-proteins and betagamma subunits, inhibited by co
      transfected alpha-transducin. The Src-family tyrosine kinase inhibitor PP1, as
      well as specific inhibition of the epidermal growth factor receptor tyrosine
      kinase (EGFR TK) by PD153035, also blocks PYY stimulation of MAPK. This pathway
      further requires protein kinase C with EGFR TK inhibition blocking PYY-induced
      protein kinase Cepsilon (PKCepsilon) translocation to the cell membrane. Finally,
      we show that PYY stimulates growth in Y1R-expressing gut epithelial cells that is
      dependent on EGFR TK activity. These results demonstrate a novel pathway
      involving G(i)/G(o) protein, EGFR and PKC to activate MAPK. Further, they support
      a role for PYY and the Y1R in regulating growth in human colonic epithelium.

PMID- 10970778
TI  - Function of the N-terminal propeptide of an aminopeptidase from Vibrio
      proteolyticus.
AB  - An aminopeptidase from Vibrio proteolyticus was translated as a preproprotein
      consisting of four domains: a signal peptide, an N-terminal propeptide, a mature
      region and a C-terminal propeptide. Protein expression and analysis of the
      activity results demonstrated that the N-terminal propeptide was essential to the
      formation of the active enzyme in Escherichia coli. Urea dissolution of inclusion
      bodies and dialysis indicated that the N-terminal propeptide could facilitate the
      correct folding of the enzyme in vitro. Using L-Leu-p-nitroanilide as the
      substrate, the kinetic parameters (k(cat) and K(m)) of the pro-aminopeptidase and
      processed aminopeptidases were analysed. The results suggested that the N
      terminal propeptide inhibited enzyme activity of the mature region. In contrast,
      the C-terminal propeptide did not show evidence of forming an active enzyme, of
      correctly folding in vitro or of inhibiting the active region.

PMID- 10970777
TI  - Disruption and overexpression of the Schizosaccharomyces pombe aph1 gene and the
      effects on intracellular diadenosine 5',5'''-P1, P4-tetraphosphate (Ap4A), ATP
      and ADP concentrations.
AB  - Diadenosine oligophosphates are ubiquitous compounds that were discovered over 30
      years ago. Diadenosine 5',5"'-P(1), P(4)-tetraphosphate (Ap(4)A) is the most
      studied member of this family, and its function in yeast is unknown. To
      investigate possible functions, we changed the intracellular Ap(4)A concentration
      in Schizosaccharomyces pombe via disruption and overexpression of the aph1 gene,
      which encodes an Ap(4)A hydrolase (Aph1). S. pombe Aph1 is 52% identical with a
      human tumour suppressor protein, Fhit, in a core region of 109 amino acids.
      Disruption of aph1 resulted in an 85% decrease in Ap(4)A hydrolase activity and a
      290-fold increase in the intracellular Ap(4)A concentration. The disruption and
      subsequent increase in intracellular Ap(4)A concentration had no significant
      effect on the growth of S. pombe. Overexpression of the S. pombe aph1 gene,
      resulting in 17- and 84-fold increases in Ap(4)A hydrolase activity above wild
      type levels, resulted in 60 and 80% decreases respectively in the intracellular
      Ap(4)A concentration. This represents the first report of a decrease in the
      intracellular Ap(4)A concentration in response to overexpression of a degradative
      enzyme in any eukaryotic organism. We describe a new S. pombe expression plasmid,
      pPOX, which was used to achieve the largest increase in expression of aph1.
      Overexpression of aph1 at the highest level resulted in a 46% increase in
      generation time in comparison with the control strain. Neither overexpression nor
      disruption had any effect on the intracellular ATP or ADP concentrations. This is
      the first report of ADP and ATP concentrations in S. pombe. These data also
      indicate that Aph1 functions in vivo to degrade Ap(4)A, and that high-level
      overexpression of this enzyme reduces the growth rate.

PMID- 10970779
TI  - Role of cationic amino acids in the Na+/dicarboxylate co-transporter NaDC-1.
AB  - The role of cationic amino acids in the Na(+)/dicarboxylate co-transporter NaDC-1
      was investigated by site-directed mutagenesis and subsequent expression of mutant
      transporters in Xenopus oocytes. Of the ten residues chosen for mutagenesis,
      eight (Lys-34, Lys-107, Arg-108, Lys-333, Lys-390, Arg-368, Lys-414 and Arg-541)
      were found to be non-essential for function or targeting. Only two conserved
      residues, Lys-84 (at the cytoplasmic end of helix 3) and Arg-349 (at the
      extracellular end of helix 7), were found to be important for transport. Both
      mutant transporters were expressed at the plasma membrane. The mutation of Lys-84
      to Ala resulted in an increased K(m) for succinate of 1.8 mM, compared with 0.3
      mM in the wild-type NaDC-1. The R349A mutant had Na(+) and citrate kinetics that
      were similar to those of the wild type. However, succinate handling in the R349A
      mutant was altered, with evidence of inhibition at high succinate concentrations.
      In conclusion, charge neutralization of Lys-84 and Arg-349 in NaDC-1 affects
      succinate handling, suggesting that these residues might have roles in substrate
      binding.

PMID- 10970780
TI  - Characterization of homocysteine metabolism in the rat liver.
AB  - Recent evidence suggests that an increased plasma concentration of the sulphur
      amino acid homocysteine is a risk factor for the development of vascular disease.
      The tissue(s) responsible for homocysteine production and export to the plasma
      are not well known. However, given the central role of the liver in amino acid
      metabolism, we developed a rat primary hepatocyte model in which homocysteine
      (and cysteine) production and export were examined. The dependence of
      homocysteine export from incubated hepatocytes on methionine concentration fitted
      well to a rectangular hyperbola, with half-maximal homocysteine export achieved
      at methionine concentrations of approx. 0.44 mM. Hepatocytes incubated with 1 mM
      methionine and 1 mM serine (a substrate for the transulphuration pathway of
      homocysteine removal) produced and exported significantly less homocysteine (25
      40%) compared with cells incubated with 1 mM methionine alone. The effects of
      dietary protein on homocysteine metabolism were also examined. Rats fed a 60%
      protein diet had a significantly increased total plasma homocysteine level
      compared with rats fed a 20% protein diet. In vitro effects of dietary protein
      were examined using hepatocytes isolated from animals maintained on these diets.
      When incubated with 1 mM methionine, hepatocytes from rats fed the high protein
      diet exported significantly more homocysteine compared with hepatocytes from rats
      fed the normal protein diet. Inclusion of serine significantly lowered
      homocysteine export in the normal protein group, but the effect was more marked
      in the high protein group. In vivo effects of serine were also examined. Rats fed
      a high protein diet enriched with serine had significantly lower total plasma
      homocysteine (25-30%) compared with controls. These data indicate a significant
      role for the liver in the regulation of plasma homocysteine levels.

PMID- 10970781
TI  - A simple method for measuring the relative force exerted by myosin on actin
      filaments in the in vitro motility assay: evidence that tropomyosin and troponin
      increase force in single thin filaments.
AB  - We have studied the effect of an internal load on the movement of actin filaments
      over a bed of heavy meromyosin (HMM) in the in vitro motility assay. Immobilized
      alpha-actinin can bind to actin filaments reversibly and ultimately stop the
      filaments from moving. Above a critical concentration of alpha-actinin, thin
      filament velocity rapidly diminished to zero. The fraction of thin motile
      filaments decreased linearly to zero with increasing alpha-actinin concentration.
      The concentration of alpha-actinin needed to stop all filaments from moving (0.8
      microg/ml with actin) was very consistent both within and between experiments. In
      the present study we have defined the 'index of retardation' as the concentration
      of alpha-actinin needed to stop all filament movement, and we propose that this
      index is a measure of the isometric force exerted by HMM on actin filaments. When
      we measured the effect of immobilized alpha-actinin on motility in the presence
      of 10 mM P(i) we found that the index of retardation was 0.62+/-0.07 (n=3) times
      that in the absence of P(i). This observation is in agreement with the reduction
      of isometric tension in chemically-skinned muscle due to P(i). In a series of
      comparative experiments we observed that tropomyosin and troponin increase the
      index of retardation and that the degree of increase depends upon the tropomyosin
      isoform studied. The index of retardation of actin is increased 1.8-fold by
      skeletal-muscle tropomyosin, and 3-fold by both cardiac-muscle and smooth-muscle
      tropomyosin. In the presence of troponin the index of retardation is 2.9-3.4-fold
      greater than that of actin with all tropomyosin isoforms.

PMID- 10970782
TI  - Surface-loop residue Lys316 in blood coagulation Factor IX is a major determinant
      for Factor X but not antithrombin recognition.
AB  - The active site of activated Factor IX (FIXa) and related blood-coagulation
      enzymes is surrounded by a number of highly variable surface loops, which
      contribute to the characteristic substrate specificity of each individual enzyme.
      FIX residue Lys(316) is located in one of these loops and mutation of this
      residue to Glu is associated with haemophilia B. In the present study we
      investigated the functional role of Lys(316) in human FIXa by analysing the
      purified and activated FIX mutants FIXa-K316E and FIXa-K316A. FIXa-K316E was
      indistinguishable from normal FIXa in binding the competitive active-site
      inhibitor p-aminobenzamidine. In addition, substitution of Glu for Lys(316) had
      no significant effect on the reactivity towards various synthetic tripeptide
      substrates. Inhibition by the macromolecular inhibitor antithrombin was only
      slightly reduced for both FIXa mutants (less than 2-fold). In contrast,
      proteolytic activity of FIXa-K316E towards the natural substrate Factor X (FX)
      was virtually lacking, while the Lys(316) to Ala mutation resulted in a more than
      10-fold reduction in FX activation. Thus residue Lys(316) plays a key role in
      FIXa activity towards FX. The requirement for Lys at position 316 for FX
      activation was also evident in the presence of the cofactor activated Factor
      VIII, although to a lesser extent than in its absence. These data demonstrate
      that Lys(316) specifically determines the reactivity of FIXa towards its natural
      substrate FX, but not to synthetic peptide substrates or antithrombin.

PMID- 10970783
TI  - Oxygen tension limits nitric oxide synthesis by activated macrophages.
AB  - Previous studies have established that constitutive calcium-dependent ('low
      output') nitric oxide synthase (NOS) is regulated by oxygen tension. We have
      investigated the role of oxygen tension in the synthesis of NO by the 'high
      output' calcium-independent NOS in activated macrophages. Hypoxia increased
      macrophage NOS gene expression in the presence of one additional activator, such
      as lipopolysaccharide or interferon-gamma, but not in the presence of both.
      Hypoxia markedly reduced the synthesis of NO by activated macrophages (as
      measured by accumulation of nitrite and citrulline), such that, at 1% oxygen
      tension, NO accumulation was reduced by 80-90%. The apparent K(m) for oxygen
      calculated from cells exposed to a range of oxygen tensions was found to be
      10.8%, or 137 microM, O(2) This value is considerably higher than the oxygen
      tension in tissues, and is virtually identical to that reported recently for
      purified recombinant macrophage NOS. The decrease in NO synthesis did not appear
      to be due to diminished arginine or cofactor availability, since arginine
      transport and NO synthesis during recovery in normoxia were normal. Analysis of
      NO synthesis during hypoxia as a function of extracellular arginine indicated
      that an altered V(max), but not K(m)(Arg), accounted for the observed decrease in
      NO synthesis. We conclude that oxygen tension regulates the synthesis of NO in
      macrophages by a mechanism similar to that described previously for the calcium
      dependent low-output NOS. Our data suggest that oxygen tension may be an
      important physiological regulator of macrophage NO synthesis in vivo.

PMID- 10970784
TI  - A new phosphospecific cell-based ELISA for p42/p44 mitogen-activated protein
      kinase (MAPK), p38 MAPK, protein kinase B and cAMP-response-element-binding
      protein.
AB  - Assaying activation of signal transduction is laborious and does not allow the
      study of large numbers of samples, essential for high-throughput drug screens or
      for large groups of patients. Using phosphospecific antibodies, we have developed
      ELISA techniques enabling non-radioactive semi-quantitative assessment of the
      activation state of p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK,
      protein kinase B and the transcription factor cAMP-response-element-binding
      protein (CREB) in 96-well plates. This assay has been termed PACE
      (phosphospecific antibody cell-based ELISA) and was used successfully for both
      adherent and suspension cells. Various stimuli induced dose-dependent enzymic
      activity of which the kinetics closely correlated with those measured via
      classical methodology. Using PACE we have now characterized for the first time
      the concentration-dependent effects of various inflammatory prostaglandins on
      CREB phosphorylation in macrophages. PACE is a straightforward and novel
      technique enabling the large-scale analysis of signal transduction.

PMID- 10970785
TI  - Biogenesis of endoplasmic reticulum proteins involved in Ca2+ signalling during
      megakaryocytic differentiation: an in vitro study.
AB  - The endoplasmic reticulum (ER) plays a key role in Ca(2+) signalling through
      Ca(2+) release via inositol 1,4,5-trisphosphate receptors (InsP(3)-Rs) and Ca(2+)
      uptake by sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs). Here, we
      investigated the organization of platelet ER and its biogenesis during
      megakaryocytopoiesis. First, erythro/megakaryoblastic MEG 01, UT7, M-O7e and CHRF
      288-11 cell lines, platelets and thrombopoietin-induced UT7-Mpl cells were
      selected for the study of SERCA2b and SERCA3 proteins by Western blotting using
      the antibodies IID8 and PL/IM430, respectively. As judged by platelet
      glycoprotein IIIa (GPIIIa) expression, an increase in SERCA3 proteins was
      observed while that of SERCA2b remained unchanged throughout maturation. Second,
      these studies were extended to the newly described alternatively spliced SERCA3a
      c RNAs and InsP(3)-Rs using the in vitro model of PMA-induced differentiation of
      MEG 01 cells. Time-course and dose-response studies showed a maximal approx. 4
      fold up-regulation of SERCA3 proteins using 10(-8) M PMA for 3 days, which
      paralleled induction of GPIIIa expression. SERCA3 induction was found to occur at
      the level of mRNA. The modulation of the different SERCA3 species (i.e. 3a, 3b
      and 3c) was isoform-specific: while SERCA3a was slightly increased, an approx. 3
      fold induction of SERCA3b, and a 4-fold induction of SERCA3c, was observed after
      24 h of PMA treatment. Isoform-specific Western blotting and/or reverse
      transcriptase PCR studies showed that InsP(3)-R types I, II and III are expressed
      in MEG 01 cells, as well as in platelets. Study of the expression of these
      InsP(3)-R types in PMA-induced MEG 01 cells revealed that: (i) InsP(3)-RI protein
      and mRNA showed no changes; (ii) InsP(3)-RII mRNA was up-regulated and peaked at
      hour 48 and (iii) InsP(3)-RIII mRNA and protein showed a transitory maximal 3-
      and 2.3-fold increase at hours 6 and 30, respectively. Upon PMA treatment of CHRF
      288-11 cells, in which GPIIIa is not induced upon treatment, a similar pattern of
      regulation of InsP(3)-R types II and III was seen, but a distinct pattern of
      SERCA3 regulation was observed. These results suggest a profound reorganization
      of ER-protein patterns during megakaryocytopoiesis and underline the role of
      SERCA3 gene regulation in the control of Ca(2+)-dependent platelet functions.

PMID- 10970787
TI  - Definition of a minimal munc18c domain that interacts with syntaxin 4.
AB  - munc18c is a critical protein involved in trafficking events associated with
      syntaxin 4 and which also mediates inhibitory effects on vesicle docking and/or
      fusion. To investigate the domains of munc18c responsible for its interaction
      with syntaxin 4, fragments of munc18c were generated and their interaction with
      syntaxin 4 examined in vivo by the yeast two-hybrid assay. In vitro protein
      protein interaction studies were then used to confirm that the interaction
      between the proteins was direct. Full-length munc18c(1-592), munc18c(1-139) and
      munc18c(1-225), but not munc18c(226-592), munc18c(1-100), munc18c(43-139) or
      munc18c(66-139), interacted with the cytoplasmic portion of syntaxin 4, Stx4(2
      273), as assessed by yeast two-hybrid assay of growth on nutritionally deficient
      media and by beta-galactosidase reporter induction. The N-terminal predicted
      helix-a-helix-b-helix-c region of syntaxin 4, Stx4(29-157), failed to interact
      with full-length munc18c(1-592), indicating that a larger portion of syntaxin 4
      is necessary for the interaction. The yeast two-hybrid results were confirmed by
      protein-protein interaction studies between Stx4(2-273) and glutathione S
      transferase fusion proteins of munc18c. Full-length munc18c(1-592), munc18c(1
      139) and munc18c(1-225) interacted with Stx4(2-273) whereas munc18c(1-100) did
      not, consistent with the yeast two-hybrid data. These data thus identify a region
      of munc18c between residues 1 and 139 as a minimal domain for its interaction
      with syntaxin 4.

PMID- 10970786
TI  - Tumour-necrosis-factor-receptor-associated factor 6, NF-kappaB-inducing kinase
      and IkappaB kinases mediate IgE isotype switching in response to CD40.
AB  - The process of IgE switching requires the prior transcription of the unrearranged
      Cepsilon gene, which leads to its recombination with the VDJ region. The
      activation of NF-kappaB by CD40 is a key process in facilitating this
      transcription by promoting the activation of the Cepsilon promoter. The present
      study explores the uncharacterized signalling pathways employed by CD40 in
      activating NF-kappaB by the overexpression of genes encoding wild-type and
      dominant-negative forms of the signalling components tumour-necrosis-factor
      receptor-associated factor 6 (TRAF-6), NF-kappaB-inducing kinase (NIK), IkappaB
      kinase (IKK)-1 and IKK-2 in the BJAB B-cell line. The overexpression of TRAF-6 or
      NIK was sufficient to activate NF-kappaB and the Cepsilon promoter, whereas their
      dominant-negative counterparts decreased the ability of CD40 to activate NF
      kappaB and the Cepsilon promoter. The overexpression of wild-type IKK-1 or IKK-2
      seemed to cause toxic effects on the cells, whereas the dominant-negative forms
      were selective in their blockade of NF-kappaB and the Cepsilon promoter. These
      results suggest that CD40 employs TRAF-6, which presumably recruits NIK, which in
      turn employs IKK-1/IKK-2 to activate NF-kappaB and the Cepsilon promoter, the
      prologue to IgE switching. Thus the findings define a crucially important pathway
      in the generation of allergic states.

PMID- 10970788
TI  - The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide
      sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and
      glucosylceramide.
AB  - We have demonstrated previously that there is an abnormal expression of
      sphingomyelin (SM) deacylase in the epidermis of patients with atopic dermatitis
      (ADe). In the present study, we have prepared N-[palmitic acid-1-(14)C]SM and N
      [palmitic acid-1-(14)C]glucosylceramide (GCer) to use as substrates and have
      quantified SM deacylase activity by detecting the release of [(14)C]palmitic acid
      in extracts of the stratum corneum or the epidermis of ADe patients. In studies
      using [palmitic acid-1-(14)C]SM as a substrate, a pH dependency of catalytic
      activity with a peak at pH 5.0 was found. Preparative SDS/PAGE using an extract
      of ADe epidermis revealed that the molecular mass of SM deacylase is 40000 Da,
      which is consistent with its apparent molecular mass of 42000 Da estimated by gel
      filtration analysis of stratum corneum extracts. Analytical isoelectric focusing
      (IEF) chromatography demonstrated that the pI values of SM deacylase, beta
      glucocerebrosidase (GlcCDase), sphingomyelinase (SMase) and acid ceramidase were
      4.2, 7.4, 7.0 and 5.7, respectively. In enzymic analysis using pI-4.2 SM
      deacylase partially purified by IEF, which had no detectable contamination with
      acid ceramidase, GlcCDase or SMase, radio-TLC analysis revealed that
      radiolabelled sphingosylphosphocholine or [1-(14)C]palmitic acid was enzymically
      liberated from [choline-methyl-(14)C]SM or N-[palmitoyl-1-(14)C]GCer,
      respectively, used as substrates. Further the pI-4.2 protein purified from
      extracts of the stratum corneum of ADe patients was able to hydrolyse N
      [palmitoyl-1-(14)C]SM and GCer, but not N-[palmitoyl-1-(14)C]ceramide. These
      results indicate that a hitherto undiscovered epidermal enzyme, termed here
      glucosylceramide sphingomyelin deacylase, is expressed in the skin of ADe
      patients, which plays an important role in ceramide deficiency (including
      acylceramides) in the stratum corneum.

PMID- 10970789
TI  - Novel triterpenoids inhibit both DNA polymerase and DNA topoisomerase.
AB  - As described previously, we found that new triterpenoid compounds, designated
      fomitellic acids A and B, which selectively inhibit the activities of mammalian
      DNA polymerases alpha and beta [Mizushina, Tanaka, Kitamura, Tamai, Ikeda,
      Takemura, Sugawara, Arai, Matsukage, Yoshida and Sakaguchi (1998) Biochem. J.
      330, 1325-1332; Tanaka, Kitamura, Mizushina, Sugawara and Sakaguchi (1998) J.
      Nat. Prod. 61, 193-197] and that a known triterpenoid, ursolic acid, is an
      inhibitor of human DNA topoisomerases I and II (A. Iida, Y. Mizushina and K.
      Sakaguchi, unpublished work). Here we report that all of these triterpenoids are
      potent inhibitors of calf DNA polymerase alpha, rat DNA polymerase beta and human
      DNA topoisomerases I and II, and show moderate inhibitory effects on plant DNA
      polymerase II and human immunodeficiency virus reverse transcriptase. However,
      these compounds did not influence the activities of prokaryotic DNA polymerases
      such as Escherichia coli DNA polymerase I or other DNA metabolic enzymes such as
      human telomerase, T7 RNA polymerase and bovine deoxyribonuclease I. These
      triterpenoids were not only mammalian DNA polymerase inhibitors but also
      inhibitors of DNA topoisomerases I and II even though the enzymic characteristics
      of DNA polymerases and DNA topoisomerases, including their modes of action, amino
      acid sequences and three-dimensional structures, differed markedly. These
      triterpenoids did not bind to DNA, suggesting that they act directly on these
      enzymes. Because the three-dimensional structures of fomitellic acids were shown
      by computer simulation to be very similar to that of ursolic acid, the DNA
      binding sites of both enzymes, which compete for the inhibitors, might be very
      similar. Fomitellic acid A and ursolic acid prevented the growth of NUGC cancer
      cells, with LD(50) values of 38 and 30 microM respectively.

PMID- 10970790
TI  - Cloning of a human cDNA encoding a novel enzyme involved in the elongation of
      long-chain polyunsaturated fatty acids.
AB  - The Saccharomyces cerevisiae protein ELO2p is involved in the elongation of
      saturated and monounsaturated fatty acids. Among several sequences with limited
      identity with the S. cerevisiae ELO2 gene, a consensus cDNA sequence was
      identified from the LifeSeq(R) database of Incyte Pharmaceuticals, Inc. Human
      liver cDNA was amplified by PCR using oligonucleotides complementary to the 5'
      and 3' ends of the putative human cDNA sequence. The resulting full-length
      sequence, termed HELO1, consisted of 897 bp, which encoded 299 amino acids.
      However, in contrast with the ELO2 gene, expression of this open reading frame in
      S. cerevisiae demonstrated that the encoded protein was involved in the
      elongation of long-chain polyunsaturated fatty acids, as determined by the
      conversion of gamma-linolenic acid (C(18:3, n-6)) into dihomo-gamma-linolenic
      acid (C(20:3, n-6)), arachidonic acid (C(20:4, n-6)) into adrenic acid (C(22:4, n
      6)), stearidonic acid (C(18:4, n-3)) into eicosatetraenoic acid (C(20:4, n-3)),
      eicosapentaenoic acid (C(20:5, n-3)) into omega3-docosapentaenoic acid (C(22:5, n
      3)) and alpha-linolenic acid (C(18:3, n-3)) into omega3-eicosatrienoic acid
      (C(20:3, n-3)). The predicted amino acid sequence of the open reading frame had
      only 29% identity with the yeast ELO2 sequence, contained a single histidine-rich
      domain and had six transmembrane-spanning regions, as suggested by hydropathy
      analysis. The tissue expression profile revealed that the HELO1 gene is highly
      expressed in the adrenal gland and testis. Furthermore, the HELO1 gene is located
      on chromosome 6, best known for encoding the major histocompatibility complex,
      which is essential to the human immune response.

PMID- 10970791
TI  - Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel
      member of the family of sugar-transport facilitators predominantly expressed in
      brain and leucocytes.
AB  - The GLUT9 gene encodes a cDNA which exhibits significant sequence similarity with
      members of the glucose transporter (GLUT) family. The gene is located on
      chromosome 9q34 and consists of 10 exons separated by short introns. The amino
      acid sequence deduced from its cDNA predicts 12 putative membrane-spanning
      helices and all the motifs (sugar-transporter signatures) that have previously
      been shown to be essential for transport activity. A striking characteristic of
      GLUT9 is the presence of two arginines in the putative helices 7 and 8 at
      positions where the organic anion transporters harbour basic residues. The next
      relative of GLUT9 is the glucose transporter GLUT8/GLUTX1 (44.8% amino acid
      identity with GLUT9). A 2.6-kb transcript of GLUT9 was detected in spleen,
      peripheral leucocytes and brain. Transfection of COS-7 cells with GLUT9 produced
      expression of a 46-kDa membrane protein which exhibited reconstitutable glucose
      transport activity and low-affinity cytochalasin-B binding. It is concluded that
      GLUT9 is a novel member of the family of sugar-transport facilitators with a
      tissue-specific function.

PMID- 10970792
TI  - In vitro glycoxidation alters the interactions between collagens and human
      polymorphonuclear leucocytes.
AB  - Glycation and glycoxidation processes, which are increased in diabetes mellitus,
      are generally considered causative mechanisms of long-term complications. With
      reference to our previous studies, type-I and -IV collagens could induce
      differentially the adhesion and stimulation of polymorphonuclear leucocytes
      (PMNs). As PMNs play a role in sustained diabetic oxidative stress, the present
      study was designed to determine whether in vitro glycoxidation of these
      macromolecules could alter PMN adhesion, activation and migration. The adhesion
      of PMNs to in vitro-glycoxidized collagens was significantly increased when
      compared with control collagens: +37% (P<0.05) and +99% (P<0.01) for collagens I
      and IV, respectively. Glycoxidized type-I collagen increased the chemotactic
      properties of PMNs without significant stimulatory effect on respiratory burst,
      whereas pre-incubation of PMNs with glycoxidized type-I collagen induced a
      priming on subsequent stimulation by N-formyl-methionyl-leucyl-phenylalanine.
      Glycoxidation of type-IV collagen suppressed its inhibitory effect on further PMN
      stimulation or migration. Collectively, these results indicate that glycoxidation
      of two major extracellular-matrix collagens considerably alters their ability to
      modulate PMN migration and production of reactive oxygen species. This imbalance
      in PMN metabolism may be a major event in the increased oxidative status that
      characterizes diabetes mellitus.

PMID- 10970793
TI  - Contribution of steroidogenic factor 1 to the regulation of cholesterol
      synthesis.
AB  - Steroidogenic factor 1 (SF-1) is an orphan member of the nuclear receptor family
      expressed in steroidogenic tissues, where it has an essential role in the
      regulation of the steroid hormone biosynthesis, adrenal and gonadal development
      and endocrine responses fundamental for reproduction. Here we show that SF-1
      regulates the transcription of cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)
      synthase gene, which is essential for the endogenous synthesis of cholesterol. We
      have identified an element located 365 bp upstream of the gene for cytosolic HMG
      CoA synthase; SF-1 binds as a monomer to this element and confers SF-1
      responsiveness to homologous and heterologous promoters. It has been shown that
      in tissues with a high demand for cholesterol to be used in steroid synthesis,
      there is a lack of correlation between the cholesterol levels and the activity of
      the limiting enzymes of the mevalonate pathway. In accord with those results, we
      observed that cholesterol synthesis from acetate and either cytosolic HMG-CoA
      mRNA expression or transcriptional activity were not changed in response to 25
      hydroxycholesterol in the SF-1-expressing steroidogenic Leydig tumour MA-10
      cells. Moreover, the overexpression of SF-1 in non-steroidogenic CV-1 cells
      renders them less sensitive to the regulatory effects of cholesterol. This
      observation led to the hypothesis that in steroidogenic tissues the expression of
      SF-1 permits high levels of endogenous synthesis of cholesterol irrespective of
      the intracellular levels of this metabolite.

PMID- 10970794
TI  - Thapsigargin suppresses phorbol ester-dependent human involucrin promoter
      activity by suppressing CCAAT-enhancer-binding protein alpha (C/EBPalpha) DNA
      binding.
AB  - Human involucrin (hINV) is a keratinocyte differentiation marker expressed in the
      suprabasal epidermal layers. In cultured keratinocytes hINV mRNA levels are
      increased 10-fold by a 24-h treatment with 50 ng/ml PMA, an agent that promotes
      keratinocyte differentiation. Previous studies show that thapsigargin (TGN), an
      agent that depletes intracellular calcium stores, inhibits keratinocyte
      differentiation. In the present study we show that TGN inhibits the PMA
      dependent, differentiation-associated, increase in hINV mRNA levels and hINV
      promoter activity. Inhibition is half-maximal at 10 nM and maximal at 100 nM TGN.
      Neither basal hINV promoter activity nor glyceraldehyde-3-phosphate dehydrogenase
      mRNA levels are inhibited. Mutation of a functionally important CAATT-enhancer
      binding protein (C/EBP) site within the hINV promoter proximal regulatory region
      eliminates the regulation, suggesting that TGN may effect C/EBP-dependent
      promoter activation. Consistent with this hypothesis, TGN inhibits C/EBPalpha
      dependent promoter activation via a mechanism that involves inhibition of
      C/EBPalpha binding to DNA without changing C/EBPalpha protein levels. These
      results suggest that TGN interferes with hINV expression by interfering with
      C/EBP transcription-factor function.

PMID- 10970795
TI  - Biological effects of menadione photochemistry: effects of menadione on
      biological systems may not involve classical oxidant production.
AB  - Because cell-mediated reduction of menadione leads to the generation of reactive
      oxygen species (ROS), this quinone is widely used to investigate the effects of
      ROS on cellular functions. We report that A549 human lung epithelial cells
      exposed to menadione demonstrate a dose-dependent increase in both intracellular
      calcium ([Ca(2+)](i)) and ROS formation. The concentrations of menadione required
      to initiate these two events are markedly different, with ROS detection requiring
      higher levels of menadione. Modulators of antioxidant defences (e.g. buthionine
      sulphoximine, 3-amino-1,2,4-triazole) have little effect on the [Ca(2+)](i)
      response to menadione, suggesting that ROS formation does not account for
      menadione-dependent alterations in [Ca(2+)](i). Additional evidence suggests that
      menadione photochemistry may be responsible for the observed [Ca(2+)](i) effects.
      Specifically: (a) EPR studies with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide
      (DMPO) show that light exposure (maximum effect at 340 nm) stimulates menadione
      dependent formation of the DMPO/(.)OH spin adduct that was not sensitive to
      antioxidant interventions; (b) DMPO inhibits menadione and light-dependent
      increases in [Ca(2+)](i); and (c) light (maximum effect at 340 nm) augments the
      deleterious effects of menadione on cell viability as determined by (51)Cr
      release. These photo effects do not appear to involve formation of singlet oxygen
      by menadione, but rather are the result of the oxidizing chemistry initiated by
      menadione in the triplet state. This work demonstrates that menadione species
      generated by photo-irradiation can exert biological effects on cellular functions
      and points to the potential importance of photochemistry in studies of menadione
      mediated cell damage.

PMID- 10970796
TI  - Identification of transient glycosylation alterations of sialylated mucin
      oligosaccharides during infection by the rat intestinal parasite Nippostrongylus
      brasiliensis.
AB  - The sialylation of the oligosaccharides from small-intestinal mucins during a 13
      day infectious cycle was studied in Sprague-Dawley rats with the parasite
      Nippostrongylus brasiliensis. Sialic acid analysis and release, permethylation
      and analysis by GC-MS of the sialylated oligosaccharides isolated from the
      'insoluble' mucin complex revealed a relative decrease (4-7-fold) of N
      glycolylneuraminic acid compared with N-acetylneuraminic acid just before
      parasite expulsion. Northern blots showed that this effect was due to the
      decreased expression of a hydroxylase converting CMP-N-acetylneuraminic acid into
      CMP-N-glycolylneuraminic acid. Analysis of other rat strains showed that this
      parasite infection also caused the same effect in these animals. Detailed
      analysis of infected Sprague-Dawley rats revealed four sialylated
      oligosaccharides not found in the uninfected animals. These new oligosaccharides
      were characterized in detail and all shown to contain the trisaccharide epitope
      NeuAc/NeuGcalpha2-3(GalNAcbeta1-4)Galbeta1 (where NeuGc is N-glycolyl neuraminic
      acid). This epitope is similar to the Sd(a)- and Cad-type blood-group antigens
      and suggests that the infection causes the induction of a GalNAcbeta1-4
      glycosyltransferase. This model for an intestinal infection suggests that the
      glycosylation of intestinal mucins is a dynamic process being modulated by the
      expression of specific enzymes during an infection process.

PMID- 10970797
TI  - Photoaffinity labelling with P3-(4-azidoanilido)uridine 5'-triphosphate
      identifies gpi3p as the UDP-GlcNAc-binding subunit of the enzyme that catalyses
      formation of GlcNAc-phosphatidylinositol, the first glycolipid intermediate in
      glycosylphosphatidylinositol synthesis.
AB  - Glycosylphosphatidylinositols (GPIs) are made by all eukaryotes. The first step
      in their synthesis is the transfer of GlcNAc from UDP-GlcNAc to
      phosphatidylinositol (PI). Four proteins in mammals and at least three in yeast
      make up a complex that carries out this reaction. Three of the proteins are
      highly conserved between yeast and mammals: the Gpi1 protein, the Pig-C/Gpi2
      protein and the Pig-A/Gpi3 protein. The function of the individual subunits is
      not known, but of the three, the Pig-A/Gpi3 proteins resemble members of a large
      family of nucleotide-sugar-utilizing glycosyltransferases. To establish whether
      Gpi3p is the UDP-GlcNAc-binding subunit of the yeast GlcNAc-PI synthetic complex,
      we tested its ability to become cross-linked to the photoactivatable substrate
      analogue P(3)-(4-azidoanilido)-uridine 5'-triphosphate (AAUTP). We report that
      Gpi3p bearing the FLAG epitope at its C-terminus becomes cross-linked to
      AAUTP[alpha-(32)P], but that Gpi2p-FLAG does not. Furthermore, Gpi3p-FLAG
      expressed in Escherichia coli is also cross-linked. These results indicate that
      Gpi3p is the UDP-GlcNAc-binding and probable catalytic subunit of the GlcNAc-PI
      synthetic complex.

PMID- 10970798
TI  - Functional and molecular modelling studies of two hereditary fructose intolerance
      causing mutations at arginine 303 in human liver aldolase.
AB  - We have identified a novel hereditary fructose intolerance mutation in the
      aldolase B gene (i.e. liver aldolase) that causes an arginine-to-glutamine
      substitution at residue 303 (Arg(303)-->Gln). We previously described another
      mutation (Arg(303)-->Trp) at the same residue. We have expressed the wild-type
      protein and the two mutated proteins and characterized their kinetic properties.
      The catalytic efficiency of protein Gln(303) is approx. 1/100 that of the wild
      type for substrates fructose 1,6-bisphosphate and fructose 1-phosphate. The
      Trp(303) enzyme has a catalytic efficiency approx. 1/4800 that of the wild-type
      for fructose 1,6-bisphosphate; no activity was detected with fructose 1
      phosphate. The mutation Arg(303)-->Trp thus substitution impairs enzyme activity
      more than Arg(303)-->Gln. Three-dimensional models of wild-type, Trp(303) and
      Gln(303) aldolase B generated by homology-modelling techniques suggest that,
      because of its larger size, tryptophan exerts a greater deranging effect than
      glutamine on the enzyme's three-dimensional structure. Our results show that the
      Arg(303)-->Gln substitution is a novel mutation causing hereditary fructose
      intolerance and provide a functional demonstration that Arg(303), a conserved
      residue in all vertebrate aldolases, has a dominant role in substrate binding
      during enzyme catalysis.

PMID- 10970799
TI  - Role of endocytosis in the transactivation of nuclear factor-kappaB by oxidized
      low-density lipoprotein.
AB  - Oxidized low-density lipoprotein (oxLDL) has been shown to modulate
      transactivation by the peroxisome proliferator-activated receptor (PPAR)-gamma
      and by nuclear factor-kappaB (NF-kappaB). In the present study, the oxLDL
      signalling pathways involved in NF-kappaB transactivation were investigated by
      utilizing a reporter construct driven by three upstream NF-kappaB binding sites,
      and various pharmacological inhibitors. OxLDL and its constituent
      lysophophatidylcholine (lysoPC) induced a rapid and transient increase in
      intracellular calcium and stimulated NF-kappaB transactivation in resting
      RAW264.7 macrophage cells in an oxidation-dependent manner. NF-kappaB activation
      by oxLDL or lysoPC was inhibited by inhibitors of protein kinase C or by a
      chelator of intracellular calcium. Tyrosine kinase or phosphatidylinositol 3
      kinase inhibitors did not block NF-kappaB transactivation. Furthermore, oxLDL
      induced NF-kappaB activity was abolished by PPAR-gamma ligands. When the
      endocytosis of oxLDL was blocked by cytochalasin B, NF-kappaB transactivation by
      oxLDL was synergistically increased, while PPAR transactivation was blocked.
      These results suggest that oxLDL activates NF-kappaB in resting macrophages via
      protein kinase C- and/or calcium-dependent pathways, and that this does not
      involve the endocytic processing of oxLDL. The endocytosis-dependent activation
      of PPAR-gamma by oxLDL may function as a route of inactivation of the oxLDL
      induced NF-kappaB signal.

PMID- 10970800
TI  - Requirement of N-glycosylation of the prostaglandin E2 receptor EP3beta for
      correct sorting to the plasma membrane but not for correct folding.
AB  - Eight heptahelical receptors have been characterized for prostaglandin (PG) D(2),
      PGE(2), PGF(2alpha), prostacyclin and thromboxane A(2). They share a sequence
      identity of 40%. All of them have potential N-glycosylation sites. The current
      study analysed the role of the two N-glycosylation sites in the rat EP3beta
      subtype PGE(2) receptor for protein folding and sorting. The N-glycosylation
      consensus sequences were eliminated by site-directed mutagenesis and receptors
      expressed in HEK-293 cells. Both potential N-glycosylation sites were used. Their
      joint elimination resulted in the synthesis of a receptor protein with full
      binding competence, biological activity and no reduction of affinity; however,
      the half-life of the non-glycosylated receptor was slightly reduced. Ligand
      binding to intact stably transfected cells and confocal laser microscopic
      immunocytochemistry showed that the glycosylated receptor was correctly inserted
      into the plasma membrane to a much larger extent than the non-glycosylated
      receptor, which tended to accumulate in the perinuclear zone of the endoplasmic
      reticulum. Inhibition of N-glycosylation with tunicamycin resulted in a similar
      perinuclear distribution of the wild-type receptor. Therefore, glycosylation of
      the EP3beta receptor seems not to be necessary for correct folding of the
      receptor protein but for the efficient transport of the receptor protein to the
      plasma membrane. This contrasts with a previous finding which described a
      reduction of the affinity for PGE(2) of the EP3alpha receptor by elimination of
      the distal glycosylation site when the receptor protein was expressed in insect
      cells.

PMID- 10970801
TI  - Role of pro-297 in the catalytic mechanism of sheep liver serine
      hydroxymethyltransferase.
AB  - Serine hydroxymethyltransferase belongs to the alpha class of pyridoxal-5'
      phosphate enzymes along with aspartate aminotransferase. Recent reports on the
      three-dimensional structure of human liver cytosolic serine
      hydroxymethyltransferase had suggested a high degree of similarity between the
      active-site geometries of the two enzymes. A comparison of the sequences of
      serine hydroxymethyltransferases revealed the presence of several highly
      conserved residues, including Pro-297. This residue is equivalent to residue Arg
      292 of aspartate aminotransferase, which binds the gamma-carboxy group of
      aspartate. In an attempt to change the reaction specificity of the
      hydroxymethyltransferase to that of an aminotransferase and to assign a possible
      reason for the conserved nature of Pro-297, it was mutated to Arg. The mutation
      decreased the hydroxymethyltransferase activity significantly (by 85-90%) and
      abolished the ability to catalyse alternative reactions, without alteration in
      the oligomeric structure, pyridoxal 5'-phosphate content or substrate binding.
      However, the concentration of the quinonoid intermediate and the extent of proton
      exchange was decreased considerably (by approx. 85%) corresponding to the
      decrease in catalytic activity. Interestingly, mutant Pro-297 Arg was unable to
      perform the transamination reaction with L-aspartate. All these results suggest
      that although Pro-297 is indirectly involved in catalysis, it might not have any
      role in imparting substrate specificity, unlike the similarly positioned Arg-292
      in aspartate aminotransferase.

PMID- 10970802
TI  - Evidence for a Menkes-like protein with a nuclear targeting sequence.
AB  - Extracts from three human cell lines were found to contain abridged Menkes
      disease gene transcripts with novel insertion sequences. The transcript variant
      that is the focus of the present study codes for a 103-residue protein containing
      the first heavy-metal-binding domain (Hmb1) of ATP7A, the Cu-ATPase associated
      with Menkes disease. This transcript variant has a 45-bp nucleotide insert
      interposed between exons 1 and 2 of ATP7A that starts with a 5' ATG that is in
      frame with the downstream ATG translation start site of ATP7A. We report here
      that the 66-bp nucleotides positioned between the upstream and downstream ATG
      sites encode 22 amino acid residues whose primary structure in part meets the
      criteria for a nuclear-localization sequence (NLS). We have referred to the
      transcript as nuclear Menkes-like (NML) 45. A green fluorescent protein (GFP)
      construct with NML45 when transfected in Chinese hamster ovary cells localized to
      the cell nucleus. A similar construct without the 66-bp segment exhibited a
      random dispersed fluorescent pattern in the cytosol. GFP constructs encoding
      ATP7A exons likewise failed to direct GFP into the cell nucleus, suggesting the
      nuclear determinant is not in an internal domain of the protein. The data suggest
      that the 22-residue segment contains an NLS for an 11.2-kDa protein with one Cu
      binding site that may function as a chaperone to transport Cu into the nucleus of
      mammalian cells.

PMID- 10970803
TI  - Cloning, characterization and tissue distribution of the rat ATP-binding cassette
      (ABC) transporter ABC2/ABCA2.
AB  - The ABC1 (ABCA) subfamily of the ATP-binding cassette (ABC) transporter
      superfamily has a structural feature that distinguishes it from other ABC
      transporters. Here we report the cloning, molecular characterization and tissue
      distribution of ABC2/ABCA2, which belongs to the ABC1 subfamily. Rat ABC2 is a
      protein of 2434 amino acids that has 44.5%, 40.0% and 40.8% identity with mouse
      ABC1/ABCA1, human ABC3/ABCA3 and human ABCR/ABCA4 respectively. Immunoblot
      analysis showed that proteins of 260 and 250 kDa were detected in COS-1 cells
      transfected with ABC2 having a haemagglutinin tag, while no band was detected in
      mock-transfected cells. After incubation with N-glycosidase F, the mobilities of
      the two proteins increased and a single band was detected, suggesting that ABC2
      is a glycoprotein. Photoaffinity labelling with 8-azido-[alpha-(32)P]ATP
      confirmed that ATP binds to the ABC2 protein in the presence of Mg(2+). RNA blot
      analysis showed that ABC2 mRNA is most abundant in rat brain. Examination of
      brain by in situ hybridization determined that ABC2 is expressed at high levels
      in the white matter, indicating that it is expressed in the oligodendrocytes.
      ABC2, therefore, is a glycosylated ABC transporter protein, and may play an
      especially important role in the brain. In addition, the N-terminal 60-amino-acid
      sequence of the human ABC1, which was missing from previous reports, has been
      determined.

PMID- 10970804
TI  - Calcium-dependent conformational stability of modules 1 and 2 of human gelsolin.
AB  - Gelsolin modulates the actin cytoskeleton in the cytoplasm and clears the
      circulation of stray filaments. In vitro, gelsolin cleaves, nucleates and caps
      actin filaments, activities that are calcium-dependent. Both cellular and
      secreted forms share a sequence of 730 residues comprising six homologous modules
      termed G1-G6. A disulphide bond is formed in secreted G2, whereas in the
      cytoplasm it remains reduced. A point mutation in G2 causes an amyloidosis with
      neurological, ophthalmological and dermatological symptoms. This mutation does
      not affect the cytoplasmic form, while the secreted form is proteolysed. As a
      first step towards understanding how gelsolin folds and functions in different
      cellular compartments, we have characterized at equilibrium the urea-induced
      unfolding of G1 and G2, with or without calcium and/or disulphide bond. G1 and G2
      both exhibit two-state unfolding behaviour and are stabilized by calcium. The
      disulphide bond also contributes to the stability of G2. In the absence of Ca(2+)
      and disulphide bond, G2 adopts a non-native conformation, suggesting that folding
      of G2 in the cytoplasm relies on the presence of surrounding modules or other
      molecular partners.

PMID- 10970805
TI  - Cytosine methylation of an Sp1 site contributes to organ-specific and cell
      specific regulation of expression of the lung epithelial gene t1alpha.
AB  - Several recent observations have suggested that cytosine methylation has a role
      in the in vivo transcriptional regulation of cell-specific genes in normal cells.
      We hypothesized that methylation regulates T1alpha, a gene expressed primarily in
      lung in adult rodents. In fetuses T1alpha is expressed in several organs,
      including the entire nervous system, but during development its expression is
      progressively restricted to lung alveolar type I epithelial cells, some
      osteoblasts and choroid plexus. Here we report that T1alpha is methylated at a
      key Sp1 site in the proximal promoter in cells and organs, including brain, where
      no gene expression is detectable. Conversely, in T1alpha-expressing cells, these
      sites are not methylated. In embryonic brain T1alpha is unmethylated and
      expressed; in adult brain the gene is methylated and not expressed. In lung
      epithelial cell lines, methylation of the T1alpha promoter in vitro decreases
      expression by approx. 50% (the maximum suppression being 100%). Analysis of
      mutated promoter constructs indicates that a single Sp1 site in the proximal
      promoter provides all or most of the methylation-sensitive gene silencing. We
      conclude that, in addition to regulation by transcription factors, cytosine
      methylation has a role in the complex expression patterns of this gene in intact
      animals and primary cells.

PMID- 10970806
TI  - Sustained activation of p42/p44 mitogen-activated protein kinase during recovery
      from simulated ischaemia mediates adaptive cytoprotection in cardiomyocytes.
AB  - Delayed cytoprotection (preconditioning) occurs 24 h after sublethal simulated
      ischaemia and reperfusion (SI/R) in neonatal rat ventricular cardiomyocytes. SI/R
      was used to investigate the role of activation of mitogen-activated protein
      kinases (MAPKs), stress-activated protein kinases (SAPKs) and phosphoinositide 3
      kinase-dependent protein kinase B (PKB)/Akt in cytoprotection. SI resulted in
      transient dual (Thr/Tyr) phosphorylation of p42/p44-MAPK and p38-MAPK, weak
      phosphorylation of p46/p54-SAPK, but no phosphorylation of PKB. 'Reperfusion'
      caused further transient phosphorylation of p38-MAPK, but sustained
      phosphorylation of p42/p44-MAPK (lasting 4 h) and of Ser(473) of PKB (lasting 2
      h). Furthermore, SI/R (24 h) induced delayed protection against lethal SI, as
      determined by an increase in cell viability ?bioreduction of MTT [3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide]? and a decrease in cell
      injury (release of creatine kinase). Both protection and phosphorylation of
      p42/p44-MAPK were blocked by the MEK-1/2 (MAPK/Erk kinase-1/2) inhibitor PD98059
      (50 microM) when given during SI/R, but not when given during SI alone. The p38
      MAPK inhibitor SB203580 (10 microM) blocked the p38-MAPK-dependent
      phosphorylation of activating transcription factor 2 in vitro, and the
      phosphoinositide 3-kinase inhibitor wortmannin (100 nM) blocked PKB
      phosphorylation on Ser(473). However, neither SB203580 nor wortmannin had any
      effect on delayed protection. Therefore sustained activation of p42/p44-MAPK
      during simulated 'reperfusion' following sublethal SI mediates preconditioning in
      cardiomyocytes independently of transient activation of p38-MAPK or sustained
      activation of PKB.

PMID- 10970807
TI  - Diffusion control of protein phosphorylation in signal transduction pathways.
AB  - Multiple signalling proteins are phosphorylated and dephosphorylated at separate
      cellular locations, which potentially causes spatial gradients of phospho
      proteins within the cell. We have derived relationships that enable us to
      estimate the extent to which a protein kinase, a phosphatase and the diffusion of
      signalling proteins control the protein phosphorylation flux and the phospho
      protein gradient. Two different cellular geometries were analysed: (1) the kinase
      is located on one planar membrane and the phosphatase on a second parallel planar
      membrane, and (2) the kinase is located on the plasma membrane of a spherical
      cell and the phosphatase is distributed homogeneously in the cytoplasm. We
      demonstrate that the control contribution of protein diffusion is potentially
      significant, given the measured rates for protein kinases, phosphatases and
      diffusion. If the distance between the membranes is 1 microm or greater, the
      control by diffusion can reach 33% or more, with the rest of the control (67%)
      shared by the kinase and the phosphatase. At distances of less than 0.1 microm,
      diffusion does not limit protein phosphorylation. For a spherical cell of radius
      10 microm, a protein diffusion coefficient of 10(-8) cm(2). s(-1) and rate
      constants for the kinase and the phosphatase of approx. 1 s(-1), control over the
      phosphorylation flux resides mainly with the phosphatase and protein diffusion,
      with approximately equal contributions of each of these. The ratio of phospho
      protein concentrations at the cell membrane and the cell centre (the dynamic
      compartmentation of the phospho-protein) is shown to be controlled by the rates
      of the protein phosphatase and of diffusion. The kinase can contribute
      significantly to the control of the absolute value of the phospho-protein
      gradient.

PMID- 10970808
TI  - The chloride effect is related to anion binding in determining the rate of iron
      release from the human transferrin N-lobe.
AB  - The major function of human transferrin is to deliver iron from the bloodstream
      to actively dividing cells. Upon iron release, the protein changes its
      conformation from 'closed' to 'open'. Extensive studies in vitro indicate that
      iron release from transferrin is very complex and involves many factors,
      including pH, the chelator used, an anion effect, temperature, receptor binding
      and intra-lobe interactions. Our earlier work [He, Mason and Woodworth (1997)
      Biochem. J. 328, 439-445] using the isolated transferrin N-lobe (recombinant N
      lobe of human transferrin comprising residues 1-337; hTF/2N) has shown that
      anions and pH modulate iron release from hTF/2N in an interdependent manner:
      chloride retards iron release at neutral pH, but accelerates the reaction at
      acidic pH. The present study supports this idea and further details the nature of
      the dual effect of chloride: the anion effect on iron release is closely related
      to the strength of anion binding to the apoprotein. The negative effect seems to
      originate from competition between chloride and the chelator for an anion-binding
      site(s) near the metal centre. With decreasing pH, the strength of anion binding
      to hTF/2N increases linearly, decreasing the contribution of competition with the
      chelator. In the meantime, the 'open' or 'loose' conformation of hTF/2N, induced
      by the protonation of critical residues such as the Lys-206/Lys-296 pair at low
      pH, enables chloride to enter the cleft and bind to exposed side chains, thereby
      promoting cleft opening and synergistically allowing removal of iron by the
      chelator, leading to a positive anion effect. Disabling one or more of the
      primary anion-binding residues, namely Arg-124, Lys-206 and Lys-296,
      substantially decreases the anion-binding ability of the resulting mutant
      proteins. In these cases, the competition for the remaining binding residue(s) is
      increased, leading to a negative chloride effect or, at most, a very small
      positive effect, even at low pH.

PMID- 10970809
TI  - Kinetics and thermodynamics of activation of quinoprotein glucose dehydrogenase
      apoenzyme in vivo and catalytic activity of the activated enzyme in Escherichia
      coli cells.
AB  - Apo-glucose dehydrogenase existing in Escherichia coli is converted to the
      holoenzyme with exogenous pyrroloquinoline quinone (PQQ) and Mg(2+). Catalytic
      behaviour of the E. coli cells with the holoenzyme is characterized by a
      Michaelis-Menten-type equation with a catalytic constant of the cell and apparent
      Michaelis constants for D-glucose and an artificial electron acceptor added to
      the E. coli suspension. The catalytic constant is expressed as the product of the
      number of molecules of the enzyme contained in an E. coli cell (z) and the
      catalytic constant of the enzyme (k(cat)), which were determined to be 2.2x10(3)
      and 6.8+/-0.8x10(3) s(-1) (phenazine methosulphate as an electron acceptor)
      respectively. Kinetics of the in vivo holoenzyme formation can be followed by an
      enzyme-electrochemical method developed by us. The rate constants for the
      reactions of apoenzyme with PQQ (k(f,PQQ)) and with Mg(2+) (k(f,Mg)) were
      determined to be 3.8+/-0.4x10(4) M(-1).s(-1) and 4. 1+/-0.9 M(-1).s(-1)
      respectively. Equilibrium constants for the binding of apoenzyme to PQQ and
      Mg(2+) were determined as the dissociation constants K(d,PQQ(Mg)) and K(d,Mg) to
      be 1.0+/-0.1 nM and 0.14+/-0.01 mM respectively. The dissociation constants for
      Ca(2+) were also determined. The holoenzyme, once formed in E. coli, returns
      gradually to the apoenzyme in the absence of PQQ and/or Mg(2+) in solution. EDTA
      was effective to remove Mg(2+) from the enzyme in the cells to deactivate the
      enzyme completely, while PQQ remained in the E. coli cells.

PMID- 10970810
TI  - The beta-subunit of the hepatocyte growth factor/scatter factor (HGF/SF) receptor
      phosphorylates and associates with CrkII: expression of CrkII enhances HGF/SF
      induced mitogenesis.
AB  - CrkII, a 40 kDa adaptor possessing a Src homology (SH)2 domain followed by two
      SH3 domains, although not endowed with catalytic activity, participates in
      intracellular signalling, presumably by activating the Ras pathway. CrkII was
      found to be phosphorylated in response to hepatocyte growth factor/scatter factor
      (HGF/SF) and to associate with the beta-subunit of the HGF receptor (MET). CrkII
      associated with p(145betaMET) via its SH2 domain. Growth-factor-receptor-bound
      protein 2 (Grb2) co-immunoprecipitated with CrkII species. By transient
      transfection of A431 human epidermoid carcinoma cells with wild-type and dominant
      negative Grb2 expression constructs lacking either the SH2 or SH3 domains, we
      have concluded that Grb2 does not contribute to the 'presentation' of CrkII to
      p(145betaMET). Overexpression of wild-type CrkII in A431 cells enhanced HGF/SF
      induced proliferation, while a CrkII dominant-negative mutant lacking the SH2
      domain prevented a similar proliferating response to HGF/SF. The effect of CrkII
      on HGF/SF-induced proliferation was also abolished in cells co-expressing CrkII
      and Son-of-sevenless lacking the guanine exchange domain, suggesting that CrkII
      is likely to induce cell proliferation partly via the Ras/mitogen-activated
      protein kinase route.

PMID- 10970812
TI  - Targeting motifs and functional parameters governing the assembly of connexins
      into gap junctions

PMID- 10970811
TI  - A novel mechanism of xylan binding by a lectin-like module from Streptomyces
      lividans xylanase 10A.
AB  - The C-terminal module of xylanase 10A from Streptomyces lividans is a family 13
      carbohydrate-binding module (CBM13). CBM13 binds mono- and oligo-saccharides with
      association constants of approximately 1x10(2) M(-1)-1x10(3) M(-1). It appears to
      be specific only for pyranose sugars. CBM13 binds insoluble and soluble xylan,
      holocellulose, pachyman, lichenan, arabinogalactan and laminarin. The association
      constant for binding to soluble xylan is (6.2+/-0. 6)x10(3)/mol of xylan polymer.
      Site-directed mutation indicates the involvement of three functional sites on
      CBM13 in binding to soluble xylan. The sites are similar in sequence, and are
      predicted to have similar structures, to the alpha, beta and gamma sites of ricin
      toxin B-chain, which is also in family 13. The affinity of a single binding site
      on CBM13 for soluble xylan is only approximately (0. 5+/-0.1)x10(3)/mol of xylan.
      The binding of CBM13 to soluble xylan involves additive and co-operative
      interactions between the three binding sites. This mechanism of binding has not
      previously been reported for CBMs binding polysaccharides. CBM13 is the first
      bacterial module from family 13 to be described in detail.

PMID- 10970813
TI  - Functional genomics and expression profiling: be there or be square.

PMID- 10970814
TI  - Basolateral potassium channels and epithelial ion transport.

PMID- 10970815
TI  - The leukotriene C(4) synthase gene and asthma.

PMID- 10970816
TI  - Pulmonary expression of the human haptoglobin gene.
AB  - Haptoglobin (Hp), a member of the acute-phase reactants, has long been known as a
      major hemoglobin-binding protein associated with hemoglobin catabolism. Recent
      studies indicate that another important biologic function of Hp is the modulation
      of the immune response. We found that Hp is expressed at high levels in specific
      cells, including alveolar macrophages and eosinophils in diseased or inflamed
      human lung tissues, but not in the normal lung. Expression of the human Hp gene
      was studied in two transgenic mouse lines carrying a 9-kb human Hp 2 gene. In
      both lines, the human Hp transgene was expressed constitutively in alveolar
      macrophages at a high level, whereas the endogenous mouse Hp was synthesized in
      airway epithelial cells. Expression of the human Hp transgene in lung cells was
      upregulated when the transgenic mice were treated with endotoxin. In humans and
      in Hp transgenic mice, human Hp messenger RNA was also detected in circulating
      eosinophils, but not in other blood cells. Our findings suggest that Hp is
      involved in a variety of lung inflammatory diseases, including respiratory
      allergy and asthma. The transgenic mouse line that overexpresses the human Hp
      gene in alveolar macrophages and eosinophils is a promising system for
      investigating the function of Hp in vivo during lung inflammation.

PMID- 10970818
TI  - Enhanced expression of the leukotriene C(4) synthase due to overactive
      transcription of an allelic variant associated with aspirin-intolerant asthma.
AB  - Aspirin-intolerant asthma (AIA), a distinct clinical syndrome affecting about 10%
      of adult asthmatics, appears to be unusually dependent on cysteine leukotriene
      (cys-LT) overproduction by pulmonary eosinophils. The gene coding for leukotriene
      (LT) C(4) synthase (LTC(4)S), the enzyme controlling cys-LT biosynthesis, exists
      as two common alleles distinguished by an A to C transversion at a site 444
      nucleotides upstream of the translation start. We tested the hypothesis that this
      single nucleotide polymorphism (SNP) affects binding of transcription factors and
      influences the transcription rate, predisposing to AIA. Gel shift assay studies
      revealed that the (-444)C allele, conferring an activator protein-2 binding
      sequence, is an additional target for a transcription factor of histone H4
      consensus. Introduction of the H4TF-2 decoy oligonucleotide into LTC(4)S
      positive, differentiated HL-60 cells decreased accumulation of LTC(4) to 68%.
      Transfection of COS-7 with promoter construct increased expression of beta
      galactosidase reporter for the (-444)C variant. The (-444)C allelic frequency was
      significantly higher in AIA patients (n = 76) as compared with matched aspirin
      tolerant asthmatics (n = 110) and healthy controls (n = 75). Patients with AIA
      had also upregulated LTC(4)S messenger RNA expression in peripheral blood
      eosinophils. An inhaled provocation test with lysine-aspirin led to an increase
      in urinary output of LTE(4), which reached statistical significance only in
      carriers of the (-444)C allele. Our results suggest that a transcription factor,
      present in dividing and bone marrow resident progenitors of eosinophils, triggers
      LTC(4)S transcription in carriers of a common (-444)C allele due to binding with
      the histone H4 promoter element of the gene. Genetic predisposition to cys-LT
      pathway upregulation, a hallmark of AIA, can be related to overactive expression
      of the LTC(4)S (-444)C allele.

PMID- 10970819
TI  - Insulin-like growth factor binding protein-6 inhibits the growth of human
      bronchial epithelial cells and increases in abundance with all-trans-retinoic
      acid treatment.
AB  - Retinoids are potent inhibitors of human bronchial epithelial (HBE) cell growth.
      Retinoids initiate signaling through activation of nuclear receptors, but the
      signal transduction pathways that mediate growth inhibition have not been
      defined. In this study, we investigated the expression of insulin-like growth
      factor (IGF)-binding protein (IGFBP)-6 as a potential mediator of retinoid
      actions. IGFBP-6 is a secreted glycoprotein that inhibits the bioavailability of
      IGFs, which are potent mitogens of HBE cells. IGFBP-6 was detected by
      immunohistochemical staining in the basal epithelial layer of human bronchial
      organ cultures, and all-trans-retinoic acid (t-RA) treatment increased the
      intensity of IGFBP-6 immunostaining. In primary cultures of HBE cells treated
      with t-RA, IGFBP-6 messenger RNA and protein levels increased within 6 and 24 h,
      respectively, and IGFBP-6 was detected in the conditioned media at 48 h. The
      effect of IGFBP-6 on HBE cell growth was investigated with a recombinant
      adenoviral vector, Ad5CMV-BP6, which expresses IGFBP-6 under the control of a
      cytomegalovirus promoter. IGFBP-6 overexpression induced a proliferative arrest
      of HBE cells with no evidence of apoptosis. These findings provide the first
      evidence that IGFBP-6 is expressed in the bronchial epithelium and that IGFBP-6
      may contribute to the biologic effects of retinoids on HBE cells.

PMID- 10970817
TI  - Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated Cl(-) secretion in
      human airway epithelia.
AB  - Ion transport defects underlying cystic fibrosis (CF) lung disease are
      characterized by impaired cyclic adenosine monophosphate (cAMP)-dependent Cl(-)
      conductance. Activation of Cl(-) secretion in airways depends on simultaneous
      activation of luminal Cl(-) channels and basolateral K(+) channels. We determined
      the role of basolateral K(+) conductance in cAMP- dependent Cl(-) secretion in
      native human airway epithelium obtained from non-CF and CF patients. CF tissues
      showed typical alterations of short-circuit currents with enhanced amiloride
      sensitive Na(+) conductance and defective cAMP-mediated Cl(-) conductance. In non
      CF tissues, Cl(-) secretion was significantly inhibited by the chromanol 293B (10
      micromol/liter), a specific inhibitor of K(V)LQT1 K(+) channels. Inhibition was
      increased after cAMP-dependent stimulation. Similar effects were obtained with
      Ba(2+) (5 mmol/liter). In patch-clamp experiments with a human bronchial
      epithelial cell line, stimulation with forskolin (10 micromol/liter)
      simultaneously activated Cl(-) and K(+) conductance. The K(+) conductance was
      reversibly inhibited by Ba(2+) and 293B. Analysis of reverse-transcribed
      messenger RNA from non-CF and CF airways showed expression of human K(V)LQT1. We
      conclude that the K(+) channel K(V)LQT1 is important in maintaining cAMP
      dependent Cl(-) secretion in human airways. Activation of K(V)LQT1 in CF airways
      in parallel with stimulation of residual CF transmembrane conductance regulator
      Cl(-) channel activity or alternative Cl(-) channels could help to circumvent the
      secretory defect.

PMID- 10970820
TI  - Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells:
      analysis of the effects of cystic fibrosis transmembrane conductance regulator
      dysfunction and bacterial virulence factors.
AB  - Airway epithelial cells can respond to infection by activating several signaling
      pathways. We examined the induction of apoptosis in response to Pseudomonas
      aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected
      cell lines. Epithelial cells in monolayers with tight junctions, confirmed by
      apical ZO-1 staining demonstrated by confocal microscopy, were entirely resistant
      to PAO1-induced apoptosis. In contrast, cell lines such as 9HTEo(-) cells that do
      not form tight junctions were susceptible, with 50% of the population apoptotic
      after 6 h of exposure to PAO1. CF transmembrane conductance regulator (CFTR)
      dysfunction caused by different mechanisms (trafficking mutations, overexpression
      of the regulatory domain or antisense constructs) did not alter rates of
      apoptosis, nor were differences apparent in terminal deoxyribonucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling detection
      of apoptotic airway cells from PAO1 infected cftr -/- or control mice. Bacterial
      expression of specific adhesins, complete lipopolysaccharide, and a functional
      type III secretion system were all necessary to evoke apoptosis even in
      susceptible epithelial cells. Unlike other mucosal surfaces, the airway
      epithelium is highly resistant to apoptosis, and this response is activated only
      when the appropriate epithelial conditions are present as well as fully virulent
      P. aeruginosa capable of coordinately expressing both adhesins and cytotoxins.

PMID- 10970821
TI  - Transcription of krox-20/egr-2 is upregulated after exposure to fibrous particles
      and adhesion in rat alveolar macrophages.
AB  - Alveolar macrophages meet various types of particulate substances deposited deep
      in the lung. We report differences in biologic responses of alveolar macrophages
      between phagocytosis of fine spherical and fibrous particles. Although titanium
      dioxide (TiO(2)) is thought to be biologically inert, the cytotoxicity of fibrous
      TiO(2) (F-TiO(2)) was much higher than spherical TiO(2) (S-TiO(2)). Differential
      display and the subsequent Northern blot analysis indicated that transcription of
      krox-20/egr-2 gene was slightly and greatly upregulated in S- and F-TiO(2)
      exposed alveolar macrophages, respectively. The messenger RNA (mRNA) level of
      krox-20/egr-2 increased up to 8 h in F-TiO(2)-exposed alveolar macrophages,
      whereas krox-20/egr-2 mRNA level was transiently increased in response to
      adhesion to the culture dish. Stimulation with lipopolysaccharide also increased
      krox-20/egr-2 mRNA level transiently, although the mRNA level rebounded after 8
      h. The analysis with 5' rapid amplification of complementary DNA ends suggested
      that there is a heterogeneity in the upstream region of this gene (krox-20/egr-2
      and krox-20H1; accession numbers AB032420 and AB032419, respectively). The
      polymerase chain reaction analysis with specific primers for krox-20/egr-2 and
      krox-20H1 indicated that both genes were almost equally upregulated after either
      adhesion to the plastic dish or phagocytosis of F-TiO(2). These results suggest
      that both krox-20/egr-2 and krox-20H1 are implicated in adhesion and
      phagocytosis, and that the expression of krox-20 may reflect interaction with
      foreign substances and adhesion in alveolar macrophages.

PMID- 10970822
TI  - Impaired distal airway development in mice lacking elastin.
AB  - Elastin is a major component of the mammalian lung, predominantly found in the
      alveoli. Destruction of alveolar elastic fibers is implicated in the pathogenic
      mechanism of emphysema in adults. These data define a role for elastin in the
      structure and function of the mature lung, and suggest that elastin is important
      for alveogenesis. To investigate the role of elastin in lung development, we
      examined mice lacking elastin (Eln-/-). At birth, the distal air sacs of Eln-/-
      lungs dilate to form abnormally large cavities. This phenotype appears before the
      synthesis and deposition of alveolar elastin, a process mediated by
      myofibroblasts and initiated after postnatal Day 4. Morphometric analyses
      demonstrate that the perinatal development of terminal airway branches is
      arrested in Eln-/- mice. The branching defect is accompanied by fewer distal air
      sacs that are dilated with attenuated tissue septae, a condition reminiscent of
      emphysema. Elastin expression in the lung parenchyma before alveogenesis is
      localized to the mesenchyme surrounding the developing airways, supporting a role
      for elastin in airway branching. Thus, in addition to its role in the structure
      and function of the mature lung, elastin is essential for pulmonary development
      and is important for terminal airway branching.

PMID- 10970823
TI  - Interleukin (IL)-5 but not immunoglobulin E reconstitutes airway inflammation and
      airway hyperresponsiveness in IL-4-deficient mice.
AB  - We studied the role of interleukin (IL)-4, IL-5, and allergen-specific
      immunoglobulin (Ig) E in the development of allergen-induced sensitization,
      airway inflammation, and airway hy-perresponsiveness (AHR). Normal, IL-4-, and IL
      5-deficient C57BL/6 mice were sensitized intraperitoneally to ovalbumin (OVA) and
      repeatedly challenged with OVA via the airways. After allergen sensitization and
      airway challenge, normal and IL-5-deficient, but not IL-4-deficient, mice
      developed increased serum levels of total and antigen-specific IgE levels and
      increased IL-4 production in the lung tissue compared with nonsensitized control
      mice. Only normal mice showed significantly increased IL-5 production in the lung
      tissue and an eosinophilic infiltration of the peribronchial regions of the
      airways, whereas both IL-4- and IL-5-deficient mice had little or no IL-5
      production and no significant eosinophilic airway inflammation. Associated with
      the inflammatory responses in the lung, only normal mice developed increased
      airway responsiveness to methacholine after sensitization and airway challenge;
      in both IL-4- and IL-5-deficient mice, airway responsiveness was similar to that
      in nonsensitized control mice. Reconstitution of sensitized, IL-4-deficient mice
      before allergen airway challenge with IL-5, but not with allergen-specific IgE,
      restored eosinophilic airway inflammation and the development of AHR. These data
      demonstrate the importance of IL-4 for allergen-driven airway sensitization and
      that IL-5, but not allergen-specific IgE, is required for development of
      eosinophilic airway inflammation and AHR after this mode of sensitization and
      challenge.

PMID- 10970824
TI  - Differential effects of extracellular matrix proteins on human airway smooth
      muscle cell proliferation and phenotype.
AB  - Mature airway smooth muscle cells are characterized by a low proliferative index
      and expression of contractile marker proteins such as smooth muscle alpha-actin
      (sm-alpha-actin), calponin, and smooth muscle myosin heavy chain (sm-MHC). In the
      present study, defined extracellular matrix (ECM) components were examined on the
      proliferative and phenotypic status of mitogen-stimulated, cultured human airway
      smooth muscle cells. The results demonstrate that although cells adhered and
      spread on plates precoated with (1 to 100 microg/ml) of fibronectin (FN),
      collagen I (Col I), laminin (LN), or Matrigel, their subsequent proliferative
      response varied qualitatively. FN and Col I enhanced proliferation in response to
      either platelet-derived growth factor (PDGF)-BB or alpha-thrombin, compared with
      cells on plastic. LN, however, reduced mitogen-stimulated proliferation. A
      similar reduction was found in cells cultured on Matrigel. The effect of ECM
      substrates on contractile phenotype was determined by examining cellular
      expression of sm-alpha-actin, sm-MHC, and calponin using immunocytochemical and
      flow cytometric methods. Approximately 75% of PDGF-BB-stimulated cells, cultured
      on LN or Matrigel, expressed sm-alpha-actin, calponin, and sm-MHC, but only 8 to
      10% stained for the Ki67 nuclear antigen proliferation marker. In contrast, more
      than 75% of cells cultured on FN or Col I were positive for Ki67 antigen, but
      only 20% were positive for contractile proteins. Flow cytometric analysis of sm
      alpha-actin and DNA content confirmed the immunocytochemical findings and showed
      that the observed reduction in sm-alpha-actin content after culture on FN or Col
      I, compared with LN and Matrigel, occurred in the majority of the cell
      population, supporting bidirectional phenotype modulation. Overall, the data
      suggest that ECM substrates modulate both proliferation and phenotype of human
      airway smooth muscle cells in culture.

PMID- 10970825
TI  - Proliferation of rat pleural mesothelial cells in response to hepatocyte and
      keratinocyte growth factors.
AB  - The proliferative response of cultured pulmonary mesothelial cells (MCs) to
      epithelial cell mitogens such as keratinocyte growth factor (KGF) and hepatocyte
      growth factor (HGF) is investigated. A cell line of rat pleural MCs and freshly
      prepared rat visceral and parietal MCs were studied. Both KGF and HGF stimulated
      thymidine uptake in the cell line when cultured for 2 d in serum-free conditions;
      the growth increase was magnified when tumor necrosis factor (TNF)-alpha was also
      added to the cultures. Adding asbestos fibers alone to MCs in culture did not
      enhance DNA synthesis by these cells. The MCs were also shown to synthesize
      significant amounts of HGF but much less KGF when cultured for 2 d. When freshly
      prepared MCs were examined, normal cell growth was more rapid in the parietal
      cells, which also had a more epithelial-type morphology. The addition of HGF and
      KGF resulted in increased DNA synthesis in each cell type, but no effect of added
      TNF-alpha was found. The results indicate that pulmonary MCs have the potential
      to proliferate in response to cytokines such as HGF and KGF that are usually
      associated with epithelial cell regeneration after injury.

PMID- 10970826
TI  - Differential induction of extracellular glutathione peroxidase and nitric oxide
      synthase 2 in airways of healthy individuals exposed to 100% O(2) or cigarette
      smoke.
AB  - Reactive oxygen species (ROS) is increased in the airway during the inhalation of
      100% O(2) or cigarette smoke and participates in the development of
      tracheobronchitis. We hypothesized that inhaled ROS upregulates local
      extracellular ROS scavenging systems or reactive molecules, e.g., nitric oxide
      (NO). Extracellular glutathione peroxidase (eGPx) is synthesized by airway
      epithelium and alveolar macrophages, secreted into the surface epithelial lining
      fluid, and functions as a first-line defense against inhaled ROS. NO, produced by
      NO synthase 2 (NOS2), combines rapidly with ROS to form reactive nitrogen species
      (RNS). In this study, human airway epithelial cells and alveolar macrophages from
      healthy individuals before and after exposure to 100% O(2) for 12 h, or from
      cigarette-smoking individuals, were evaluated for eGPx and NOS2 messenger RNA
      (mRNA) expression. Hyperoxia increased NOS2 mRNA in airway epithelial cells by
      2.5-fold but did not increase eGPx mRNA. In contrast, cigarette smoke upregulated
      eGPx mRNA over 2-fold in airway epithelial cells and alveolar macrophages but did
      not affect NOS2 expression. In vitro exposure of respiratory epithelial cells to
      ROS or RNS also increased eGPx expression. These findings define distinct
      molecular responses in the airway to different inhaled ROS, which likely
      influences the susceptibility of the airway to oxidative injury.

PMID- 10970827
TI  - Profiling the downstream genes of tumor suppressor PTEN in lung cancer cells by
      complementary DNA microarray.
AB  - The phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor
      suppressor gene with sequence homology to tyrosine phosphatases and the
      cytoskeletal proteins tensin and auxilin. PTEN has recently been shown to inhibit
      cell migration and the spreading and formation of focal adhesions. This study
      investigated the role of PTEN in carcinoma invasion in a lung-cancer cell line
      and examined the downstream genes regulated by PTEN. We have previously
      established a cell-line model in human lung adenocarcinoma with different
      invasive abilities and metastatic potentials. Examining PTEN gene expression in
      these cell lines, we found that a homozygous deletion in exon 5 is associated
      with high invasive ability. We then constructed stable constitutive and inducible
      wild-type PTEN-overexpressed transfectants in the highly invasive cell line CL(1
      5). We found that an overexpression of PTEN can inhibit invasion in lung cancer
      cells. To further explore the downstream genes regulated by PTEN, a high-density
      complementary DNA (cDNA) microarray technique was used to profile gene changes
      after PTEN overexpression. Our results indicate a panel of genes that can be
      modulated by PTEN. PTEN overexpression downregulated genes, including integrin
      alpha(6), laminin beta(3), heparin-binding epidermal growth factor-like growth
      factor, urokinase-type plasminogen activator, myb protein B, Akt2, and some
      expressed sequence tag (EST) clones. In contrast, PTEN overexpression upregulated
      protein phosphatase 2A1B, ubiquitin protease (unph), secreted phosphoprotein 1,
      leukocyte elastase inhibitor, nuclear factor-kappaB, cyclic adenosine
      monophosphate response element binding protein, DNA ligase 1, heat shock protein
      90, and some EST genes. Northern hybridization and flow cytometry analysis also
      confirmed that PTEN overexpression results in the reduced expression of the
      integrin alpha(6) subunit. The results of this study indicate that PTEN
      overexpression may inhibit lung cancer invasion by downregulation of a panel of
      genes including integrin alpha(6). The cDNA microarray technique may be an
      effective tool to study the downstream function of a tumor suppressor gene.

PMID- 10970828
TI  - Secretory leukoprotease inhibitor augments hepatocyte growth factor production in
      human lung fibroblasts.
AB  - Secretory leukoprotease inhibitor (SLPI), an 11.7-kD nonglycosylated serine
      protease inhibitor, is produced and released into the fluids of mucosal surfaces
      including human lung. It comprises two domains with homologous amino acid
      sequences: the N-terminal domain possessing antibacterial activity, and the C
      terminal domain with antiprotease activity. Here we report the positive
      regulation of hepatocyte growth factor (HGF) production in human lung fibroblasts
      exerted by SLPI or its C-terminal domain under physiologic concentrations (1 to
      10 microM). This HGF production by SLPI was unaffected by the addition of
      interleukin (IL)-1 receptor antagonist. In contrast, human skin fibroblasts
      exerted no SLPI-stimulated increase in HGF production, despite the fact that IL
      1beta increased HGF production with an intensity similar to that of human lung
      fibroblasts. Both the time-course and dose-response studies in human lung
      fibroblasts revealed that the induction of HGF messenger RNA (mRNA) and protein
      occurred in parallel, indicating that the mechanism existed at the steady-state
      mRNA level. A synthetic elastase inhibitor failed to induce HGF, but alpha(1)
      antitrypsin also stimulated HGF production in lung fibroblasts. Inactivation of
      the antiprotease activity of SLPI or its C-terminal domain by an oxidizing agent
      (N-chlorosuccinimide) abolished their stimulatory effect on HGF production. These
      findings demonstrate that SLPI exerts a novel HGF induction and functions as an
      anti-inflammatory and regenerative factor in addition to its role in protease
      inhibition.

PMID- 10970829
TI  - Phagocytosis of crocidolite asbestos induces oxidative stress, DNA damage, and
      apoptosis in mesothelial cells.
AB  - Phagocytosis of asbestos fibers may be a necessary step for asbestos-induced
      injury to mesothelial cells, but this has not been established because
      quantification of fiber uptake is difficult and ways to increase fiber
      phagocytosis without also increasing total dose were not available. We quantified
      phagocytosis by counting intracellular fibers after removing adherent fibers with
      trypsin; we selectively increased fiber phagocytosis by coating crocidolite
      asbestos fibers with the adhesive serum protein vitronectin (VN), which we have
      shown increases fiber uptake via integrins. We measured various aspects of
      asbestos-induced cytotoxicity: intracellular oxidation by the shift of
      fluorescence of cells loaded with an oxidative probe, DNA strand breakage by the
      alkaline unwinding ethidium bromide fluorometric assay, apoptosis by annexin V
      binding and by nuclear morphology, and cell-cycle progression. We found that,
      compared with control fibers or particles, asbestos increased intracellular
      oxidation, DNA strand breakage, and apoptosis. Selective increases in fiber
      uptake by VN-coating of the fibers further increased the oxidation, DNA strand
      breakage, and apoptosis, and induced a cell-cycle arrest in G2/M. Selective
      decreases in fiber uptake by cytochalasin or by integrin blockade with RGD
      peptides inhibited several of these measures of injury. We conclude that
      phagocytosis is important and perhaps necessary for asbestos-induced injury to
      mesothelial cells.

PMID- 10970830
TI  - The effect of transendothelial migration on eosinophil function.
AB  - In bronchial asthma, eosinophils found in the airways have an enhanced
      inflammatory capacity. We hypothesized that, at least in part, changes in
      functional phenotype are due to the effect of transendothelial migration. To
      model in vivo eosinophil trafficking to the lung, we cultured human pulmonary
      microvascular endothelial cell (HPMEC) monolayers on Transwell filters. The
      HPMECs were activated with interleukin (IL)-1beta to increase cell expression of
      intercellular adhesion molecule (ICAM)-1 and, hence, eosinophil transmigration.
      Peripheral blood eosinophils from allergic patients were added to HPMEC-covered
      Transwell filters and incubated for 3 h at 37 degrees C. The eosinophils were
      collected from below (migrated cells) and above (nonmigrated cells) the HPMEC
      monolayer to determine surface receptor expression, in vitro survival, and
      oxidative burst. Eosinophils never exposed to HPMECs were used as controls.
      Eosinophil cell surface expression of CD69, human leukocyte-associated antigen-DR
      (HLA-DR), and CD54 (ICAM-1) was significantly increased after transendothelial
      migration through IL-1beta-treated HPMECs compared with control cells (CD69:
      P<0.0005; HLA-DR and CD54: P<0.05) and nonmigrated eosinophils (CD69 and HLA-DR:
      P<0.05). Moreover, the percent in vitro survival (48 h) of migrated eosinophils
      was also significantly greater (P<0.0001 by trypan blue exclusion, P< 0.05 by
      flow cytometry) than that of control or nonmigrated eosinophils. Prolonged
      survival of migrated eosinophils was inhibited by addition of anti-granulocyte
      macrophage colony-stimulating factor (GM-CSF) antibodies (P<0.05) to the 48-h
      survival culture, suggesting that autocrine production of GM-CSF was, at least
      partially, responsible for increased eosinophil survival. Although GM-CSF protein
      was not measurable in survival culture supernates, GM-CSF messenger RNA (mRNA)
      was expressed in both nonmigrated and migrated eosinophils but not in control
      cells. Similarly, the eosinophils' oxidative burst induced by platelet-activating
      factor, formylmethionyl leucylphenylalanine, or phorbol myristate acetate was
      equally, and significantly, increased in both nonmigrated and migrated
      eosinophils (P<0.05 versus control). Therefore, whereas exposure of eosinophils
      to cytokine-activated HPMECs can increase surface receptor expression, in vitro
      survival, GM-CSF mRNA, and the respiratory burst, transendothelial migration can
      further potentiate receptor expression and survival in migrated cells. These
      results suggest that the process of transendothelial migration selectively
      participates in determining the eventual phenotype of airway eosinophils.

PMID- 10970831
TI  - Neutrophil transmigration across human airway epithelial monolayers: mechanisms
      and dependence on electrical resistance.
AB  - To examine neutrophil transepithelial migration in the basolateral-to-luminal
      direction, bronchial epithelial cells (16HBE) were grown at an air-medium
      interface on the lower face of permeable supports, and resistance across each
      membrane was recorded before measuring neutrophil transmigration over 2 h.
      Subconfluent monolayers (resistance < 250 Omega) permitted high spontaneous
      migration of neutrophils (7.4+/-1%), which was further enhanced (29.7+/-3%) in
      response to interleukin (IL)-8 (100 ng/ml). Confluent monolayers (250 to 700
      Omega) showed low spontaneous migration (2+/- 0.5%) but responded markedly to IL
      8 (12.4+/-1.3%). Left in culture, 16HBE resistances continued to increase and
      were associated with minimal spontaneous migration (< 0.5%) or responses to IL-8.
      Using cells in the 250 to 700 Omega range, neutrophil migration to IL-8 was dose
      dependent and was enhanced when epithelial cells were incubated with a
      combination of tumor necrosis factor-alpha and interferon-gamma. Neutrophil
      migration was stimulus-specific and was reduced by preincubation of epithelial
      cells with a F(ab')(2) anti-intercellular adhesion molecule (ICAM)-1, or by
      preincubation of neutrophils with anti-CD18, anti-CD11a, anti-CD11b, or anti
      CD11c, but not by anti-CD11d, indicating a role for beta(2)-integrin-ICAM-1
      interaction in the migration process.

PMID- 10970832
TI  - Exaggerated activation of nuclear factor-kappaB and altered IkappaB-beta
      processing in cystic fibrosis bronchial epithelial cells.
AB  - In cystic fibrosis (CF), inflammatory mediator production by airway epithelial
      cells is a critical determinant of chronic airway inflammation. To determine
      whether altered signal transduction through the nuclear factor (NF)-kappaB
      pathway occurs in CF epithelial cells and results in excessive generation of
      inflammatory cytokines, we evaluated tumor necrosis factor (TNF)-alpha-induced
      production of the NF-kappaB-dependent cytokine interleukin (IL)-8 and activation
      of NF-kappaB in three different human bronchial epithelial cell lines: (1) BEAS
      cells that express wild-type CF transmembrane conductance regulator (CFTR), (2)
      IB3 cells with mutant CFTR, and (3) C38 cells, which are "corrected" IB3 cells
      complemented with wild-type CFTR. Treatment of cells with TNF-alpha (30 ng/ml)
      resulted in markedly elevated NF-kappaB activation and production of IL-8 by IB3
      cells compared with BEAS and C38 cells. Despite the differences in NF- kappaB
      activation, no differences in basal levels of IkappaB-alpha or TNF-alpha- induced
      IkappaB-alpha processing and degradation were detected among the cell lines. In
      contrast, the basal level of IkappaB-beta was increased in the IB3 cells.
      Treatment with TNF-alpha resulted in increased formation of hypophosphorylated
      IkappaB-beta and increased nuclear localization of IkappaB-beta in IB3 cells
      compared with the other cell types. These findings provide additional evidence of
      a dysregulated inflammatory response in CF.

PMID- 10970833
TI  - Endothelin-1 changes polymorphonuclear leukocytes' deformability and CD11b
      expression and promotes their retention in the lung.
AB  - Endothelin (ET)1 influences polymorphonuclear leukocyte (PMN)- endothelial cell
      interactions. The aim of this study was to examine the effect of ET-1 on factors
      that influence PMN-endothelial interaction and retention in the lung both in
      vitro and in vivo. In vitro, high concentration of ET-1 (> or = 10(-8) M) rapidly
      increased PMN F-actin content (10(-7) M: 58 +/- 6% increase, P<0.01), whereas
      lower concentration of ET-1 (< or = 10(-9) M) caused a small but consistent
      decrease in F-actin content (10(-10) M: 6.9+/-1.5% decrease, P< 0.01).
      Preincubation of PMNs with the nitric oxide donor sodium nitroprusside (SNP)
      inhibited the F-actin content increase by 10(-7) M of ET-1 (P<0.01), and enhanced
      the F-actin content decrease by 10(-10) M of ET-1 (P<0.01). Preincubation of PMNs
      with Nomega-nitro-L-arginine methylester prevented the F-actin content decrease
      by 10(-10) M of ET-1. ET-1 (10(-7) M) reduced the deformability of PMNs (P<0.01),
      which was inhibited by preincubation of PMNs with SNP (P<0.05). ET-1 (10(-9) to
      10(-7) M) increased CD11b expression of PMNs (P<0.01), which was inhibited by
      preincubation of PMNs with SNP. In vivo studies showed that the retention of PMNs
      treated with ET-1 increased from 45+/-8 to 70+/-5% compared with naive PMNs
      during their first pass through the lung (P<0.05). We conclude that ET-1 changes
      the F-actin content, the deformability, and the CD11b expression of PMNs in a
      dose-dependent fashion and that this leads to increased PMN sequestration in
      pulmonary microvessels.

PMID- 10970834
TI  - Irradiation-induced expression of hyaluronan (HA) synthase 2 and hyaluronidase 2
      genes in rat lung tissue accompanies active turnover of HA and induction of types
      I and III collagen gene expression.
AB  - Hyaluronan (HA) is a linear glycosaminoglycan that accumulates in the
      interstitium of injured lung and inhibits gas exchange between air and blood. In
      the present study we investigated the molecular mechanisms behind the local
      turnover of HA during the early phase of irradiation-evoked lung fibrosis in
      rats. Irradiation with a single dose of 30 Gy to the lower part of the right lung
      of rats induced an accumulation of HA in bronchoalveolar lavage fluid 6 wk after
      irradiation, followed by return to almost normal levels at 10 wk after
      irradiation. This was parallelled with a transient downregulation of HA receptors
      on alveolar macrophages (AMs); 4 and 6 wk after irradiation the binding of
      [(3)H]HA to AMs was decreased to about 50% of that of AMs from nonirradiated
      control rats, returning to almost normal level at 10 wk after irradiation.
      Analysis of the expression of rat HA synthase (HAS) isoforms (rHAS1, rHAS2, and
      rHAS3) and rat hyaluronidases (rHYAL1 and rHYAL2) by Northern blotting revealed
      an upregulation of rHAS2 messenger RNA at 4, 6, and 10 wk after irradiation, but
      a progressive decrease in the constitutive expression of rHYAL2 at 6 and 10 wk
      after irradiation; rHAS1 was undetectable, whereas rHAS3 and rHYAL1 were faintly
      detectable. Although transforming growth factor-beta1 stimulated HA production by
      normal lung fibroblasts, it inhibited HYAL activity in lysosomes and HYAL
      activity released into the culture media. Another interesting observation was
      that HA fragments, which likely result from the action of HYAL, induced
      expression of types I and III collagen genes. Our results indicate that rHAS2 and
      rHYAL2 are involved in the turnover of HA during the early phase of lung injury
      and that rHAS2 and rHYAL2 as well as HA fragments may play important roles in the
      pathogenesis of lung fibrosis.

PMID- 10970835
TI  - Immunologic characterization of normal human pleural macrophages.
AB  - Human pleural macrophages (PLM) have been studied in effusions, but little is
      known about normal human PLM. We therefore analyzed resting human PLM recovered
      by lavage before lobe resection from patients with a central bronchial tumor, not
      involving the pleura, and from patients with pulmonary chondroma, intrapulmonary
      hemorrhage, and pneumothorax. Analysis of surface antigens, phagocytosis
      capacity, and cytokine production was done in comparison to the regular CD14(++)
      blood monocytes and the recently described blood monocyte subset CD14(+)CD16(+)
      monocytes. When defining fluorescence intensity for the various markers on
      CD14(++) monocytes as 100%, the PLM gave the following pattern: CD14, 45%; CD32,
      200%; CD64, 72%; CD11b, 128%; CD33, 74%; CD54, 299%; and HLA-DR, 1,906%. When
      CD16 on the CD14(+)CD16(+) monocytes was set as 100%, the level of CD16
      expression on PLM was 7.7%. Taken together, when compared to blood monocytes, PLM
      appear to represent a cell-type intermediate of regular CD14(++) monocytes and
      the CD14(+)CD16(+) subset. In functional studies, we demonstrate that PLM can
      perform efficient Fc-receptor-mediated phagocytosis of antibody-coated sheep red
      blood cells. Compared with blood monocytes, the capacity of PLM to produce tumor
      necrosis factor is similar, but a striking finding in PLM was the constitutive
      interleukin-10 messenger RNA expression that could not be substantially increased
      by lipopolysaccharide stimulation. This first characterization of normal,
      noneffusion human PLM can form the basis for a better interpretation of findings
      in malignant and inflammatory exudates.

PMID- 10970836
TI  - Evidence of a molecular barrier limiting susceptibility of humans, cattle and
      sheep to chronic wasting disease.
AB  - Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE)
      of deer and elk, and little is known about its transmissibility to other species.
      An important factor controlling interspecies TSE susceptibility is prion protein
      (PrP) homology between the source and recipient species/genotypes. Furthermore,
      the efficiency with which the protease-resistant PrP (PrP-res) of one species
      induces the in vitro conversion of the normal PrP (PrP-sen) of another species to
      the protease-resistant state correlates with the cross-species transmissibility
      of TSE agents. Here we show that the CWD-associated PrP-res (PrP(CWD)) of cervids
      readily induces the conversion of recombinant cervid PrP-sen molecules to the
      protease-resistant state in accordance with the known transmissibility of CWD
      between cervids. In contrast, PrP(CWD)-induced conversions of human and bovine
      PrP-sen were much less efficient, and conversion of ovine PrP-sen was
      intermediate. These results demonstrate a barrier at the molecular level that
      should limit the susceptibility of these non-cervid species to CWD.

PMID- 10970837
TI  - Genome-wide variation of the somatic mutation frequency in transgenic plants.
AB  - In order to analyse the frequency of point mutations in whole plants, several
      constructs containing single nonsense mutations in the beta-glucuronidase (uidA)
      gene were used to generate transgenic Arabidopsis thaliana plants. Upon
      histochemical staining of transgenic plants, sectors indicative of transgene
      reactivation appeared. Reversion frequencies were in the range of 10(-7)-10(-8)
      events per base pair, exceeding the previous estimates for other eukaryotes at
      least 100-fold. The frequency was dependent on the position of the mutation
      substrate within the transgene and the position of the transgene within the
      Arabidopsis genome. An inverse relationship between the level of transgene
      transcription and mutation frequency was observed in single-copy lines. DNA
      damaging factors induced the mutation frequency by a factor of up to 56 for UV-C,
      a factor of 3 for X-rays and a factor of 2 for methyl methanesulfonate. This
      novel plant mutation-monitoring system allowed us to measure the frequencies of
      point mutation in whole plants and may be used as an alternative or complement to
      study the mutagenicity of different environmental factors on the higher
      eukaryote's genome.

PMID- 10970838
TI  - Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with
      myotonic dystrophy.
AB  - Myotonic dystrophy (DM1) is an autosomal dominant neuromuscular disorder
      associated with a (CTG)(n) expansion in the 3'-untranslated region of the DM1
      protein kinase (DMPK) gene. To explain disease pathogenesis, the RNA dominance
      model proposes that the DM1 mutation produces a gain-of-function at the RNA level
      in which CUG repeats form RNA hairpins that sequester nuclear factors required
      for proper muscle development and maintenance. Here, we identify the triplet
      repeat expansion (EXP) RNA-binding proteins as candidate sequestered factors. As
      predicted by the RNA dominance model, binding of the EXP proteins is specific for
      dsCUG RNAs and proportional to the size of the triplet repeat expansion.
      Remarkably, the EXP proteins are homologous to the Drosophila muscleblind
      proteins required for terminal differentiation of muscle and photoreceptor cells.
      EXP expression is also activated during mammalian myoblast differentiation, but
      the EXP proteins accumulate in nuclear foci in DM1 cells. We propose that DM1
      disease is caused by aberrant recruitment of the EXP proteins to the DMPK
      transcript (CUG)(n) expansion.

PMID- 10970839
TI  - Structural basis of the membrane-targeting and unmasking mechanisms of the
      radixin FERM domain.
AB  - Radixin is a member of the ezrin/radixin/moesin (ERM) family of proteins, which
      play a role in the formation of the membrane-associated cytoskeleton by linking
      actin filaments and adhesion proteins. This cross-linking activity is regulated
      by phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) in the
      downstream of the small G protein Rho. The X-ray crystal structures of the
      radixin FERM domain, which is responsible for membrane binding, and its complex
      with inositol-(1,4, 5)-trisphosphate (IP3) have been determined. The domain
      consists of three subdomains featuring a ubiquitin-like fold, a four-helix bundle
      and a phosphotyrosine-binding-like domain, respectively. These subdomains are
      organized by intimate interdomain interactions to form characteristic grooves and
      clefts. One such groove is negatively charged and so is thought to interact with
      basic juxta-membrane regions of adhesion proteins. IP3 binds a basic cleft that
      is distinct from those of pleckstrin homology domains and is located on a
      positively charged flat molecular surface, suggesting an electrostatic mechanism
      of plasma membrane targeting. Based on the structural changes associated with IP3
      binding, a possible unmasking mechanism of ERM proteins by PIP2 is proposed.

PMID- 10970840
TI  - Amalgam is a ligand for the transmembrane receptor neurotactin and is required
      for neurotactin-mediated cell adhesion and axon fasciculation in Drosophila.
AB  - Neurotactin (NRT), a member of the cholinesterase-homologous protein family, is a
      heterophilic cell adhesion molecule that is required for proper axon guidance
      during Drosophila development. In this study, we identify amalgam (AMA), a member
      of the immunoglobulin superfamily, as a ligand for the NRT receptor. Using
      transfected Schneider 2 cells and embryonic primary cultures, we demonstrate that
      AMA is a secreted protein. Furthermore, AMA is necessary for NRT-expressing cells
      both to aggregate with themselves and to associate with embryonic primary culture
      cells. Aggregation assays performed with truncated NRT molecules reveal that the
      integrity of the cholinesterase-like extracellular domain was not required either
      for AMA binding or for adhesion, with only amino acids 347-482 of the
      extracellular domain being necessary for both activities. Moreover, the NRT
      cytoplasmic domain is required for NRT-mediated adhesion, although not for AMA
      binding. Using an ama-deficient stock, we find that ama function is not essential
      for viability. Pupae deficient for ama do exhibit defasciculation defects of the
      ocellar nerves similar to those found in nrt mutants.

PMID- 10970841
TI  - Bacterial SLH domain proteins are non-covalently anchored to the cell surface via
      a conserved mechanism involving wall polysaccharide pyruvylation.
AB  - Several bacterial proteins are non-covalently anchored to the cell surface via an
      S-layer homology (SLH) domain. Previous studies have suggested that this cell
      surface display mechanism involves a non-covalent interaction between the SLH
      domain and peptidoglycan-associated polymers. Here we report the characterization
      of a two-gene operon, csaAB, for cell surface anchoring, in Bacillus anthracis.
      Its distal open reading frame (csaB) is required for the retention of SLH
      containing proteins on the cell wall. Biochemical analysis of cell wall
      components showed that CsaB was involved in the addition of a pyruvyl group to a
      peptidoglycan-associated polysaccharide fraction, and that this modification was
      necessary for binding of the SLH domain. The csaAB operon is present in several
      bacterial species that synthesize SLH-containing proteins. This observation and
      the presence of pyruvate in the cell wall of the corresponding bacteria suggest
      that the mechanism described in this study is widespread among bacteria.

PMID- 10970843
TI  - The CXXCXXC motif determines the folding, structure and stability of human Ero1
      Lalpha.
AB  - The presence of correctly formed disulfide bonds is crucial to the structure and
      function of proteins that are synthesized in the endoplasmic reticulum (ER).
      Disulfide bond formation occurs in the ER owing to the presence of several
      specialized catalysts and a suitable redox potential. Work in yeast has indicated
      that the ER resident glycoprotein Ero1p provides oxidizing equivalents to newly
      synthesized proteins via protein disulfide isomerase (PDI). Here we show that
      Ero1-Lalpha, the human homolog of Ero1p, exists as a collection of oxidized and
      reduced forms and covalently binds PDI. We analyzed Ero1-Lalpha cysteine mutants
      in the presumed active site C(391)VGCFKC(397). Our results demonstrate that this
      motif is important for protein folding, structural integrity, protein half-life
      and the stability of the Ero1-Lalpha-PDI complex.

PMID- 10970842
TI  - A novel Golgi membrane protein is part of a GTPase-binding protein complex
      involved in vesicle targeting.
AB  - Through two-hybrid interactions, protein affinity and localization studies, we
      previously identified Yip1p, an integral yeast Golgi membrane protein able to
      bind the Ras-like GTPases Ypt1p and Ypt31p in their GDP-bound conformation. In a
      further two-hybrid screen, we identified Yif1p as an interacting factor of Yip1p.
      We show that Yif1p is an evolutionarily conserved, essential 35.5 kDa
      transmembrane protein that forms a tight complex with Yip1p on Golgi membranes.
      The hydrophilic N-terminal half of Yif1p faces the cytosol, and according to two
      hybrid analyses can interact with the transport GTPases Ypt1p, Ypt31p and Sec4p,
      but in contrast to Yip1p, this interaction is dispensable for Yif1 protein
      function. Loss of Yif1p function in conditional-lethal mutants results in a block
      of endoplasmic reticulum (ER)-to-Golgi protein transport and in an accumulation
      of ER membranes and 40-50 nm vesicles. Genetic analyses suggest that Yif1p acts
      downstream of Yip1p. It is inferred that Ypt GTPase binding to the Yip1p-Yif1p
      complex is essential for and precedes vesicle docking and fusion.

PMID- 10970844
TI  - CtrA mediates a DNA replication checkpoint that prevents cell division in
      Caulobacter crescentus.
AB  - Coordination of DNA replication and cell division is essential in order to ensure
      that progeny cells inherit a full copy of the genome. Caulobacter crescentus
      divides asymmetrically to produce a non-replicating swarmer cell and a
      replicating stalked cell. The global response regulator CtrA coordinates DNA
      replication and cell division by repressing replication initiation and
      transcription of the early cell division gene ftsZ in swarmer cells. We show that
      CtrA also mediates a DNA replication checkpoint of cell division by regulating
      the late cell division genes ftsQ and ftsA. CtrA activates transcription of the
      P(QA) promoter that co-transcribes ftsQA, thus regulating the ordered expression
      of early and late cell division proteins. Cells inhibited for DNA replication are
      unable to complete cell division. We show that CtrA is not synthesized in pre
      divisional cells in which replication has been inhibited, preventing the
      transcription of P(QA) and cell division. Replication inhibition prevents the
      activation of the ctrA P2 promoter, which normally depends on CtrA
      phosphorylation. This suggests the possibility that CtrA phosphorylation may be
      affected by replication inhibition.

PMID- 10970845
TI  - Residual Cdc2 activity remaining at meiosis I exit is essential for meiotic M-M
      transition in Xenopus oocyte extracts.
AB  - To investigate the regulatory mechanisms of the cell cycle transition from M
      phase to M phase in meiotic cycles, a Xenopus oocyte extract that performs the M
      M transition has been developed. Using the meiotic extract, we found that a low
      level of Cdc2 activity remained at the exit of meiosis I (MI), due to incomplete
      degradation of cyclin B. The inactivation of the residual Cdc2 activity induced
      both entry into S phase and tyrosine phosphorylation on Cdc2 after MI.
      Quantitative analysis demonstrated that a considerable amount of Wee1 was present
      at the MI exit and Cdc2 inhibitory phosphorylation during this period was
      suppressed by the dominance of Cdc2 over Wee1. Consistently, the addition of more
      than a critical amount of Wee1 to the extract induced Cdc2 inhibitory
      phosphorylation, changing the M-M transition into an M-S-M transition. Thus, the
      Cdc2 activity remaining at MI exit is required for suppressing entry into S phase
      during the meiotic M-M transition period.

PMID- 10970846
TI  - Cbk1p, a protein similar to the human myotonic dystrophy kinase, is essential for
      normal morphogenesis in Saccharomyces cerevisiae.
AB  - We have studied the CBK1 gene of Saccharomyces cerevisiae, which encodes a
      conserved protein kinase similar to the human myotonic dystrophy kinase. We have
      shown that the subcellular localization of the protein, Cbk1p, varies in a cell
      cycle-dependent manner. Three phenotypes are associated with the inactivation of
      the CBK1 gene: large aggregates of cells, round rather than ellipsoidal cells and
      a change from a bipolar to a random budding pattern. Two-hybrid and extragenic
      suppressor studies have linked Cbk1p with the transcription factor Ace2p, which
      is responsible for the transcription of chitinase. Cbk1p is necessary for the
      activation of Ace2p and we have shown that the aggregation phenotype is due to a
      lack of chitinase expression. The random budding pattern and the round cell
      phenotype of the CBK1 deletion strain show that in addition to its role in
      regulating chitinase expression via Ace2p, Cbk1p is essential for a wild-type
      morphological development of the cell.

PMID- 10970847
TI  - Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle
      progression.
AB  - Complexes of D-type cyclins and cdk4 or 6 are thought to govern progression
      through the G(1) phase of the cell cycle. In Drosophila, single genes for Cyclin
      D and Cdk4 have been identified, simplifying genetic analysis. Here, we show that
      Drosophila Cdk4 interacts with Cyclin D and the Rb homolog RBF as expected, but
      is not absolutely essential. Flies homozygous for null mutations develop to the
      adult stage and are fertile, although only to a very limited degree.
      Overexpression of inactive mutant Cdk4, which is able to bind Cyclin D, does not
      enhance the Cdk4 mutant phenotype, confirming the absence of additional Cyclin D
      dependent cdks. Our results indicate, therefore, that progression into and
      through the cell cycle can occur in the absence of Cdk4. However, the growth of
      cells and of the organism is reduced in Cdk4 mutants, indicating a role of D-type
      cyclin-dependent protein kinases in the modulation of growth rates.

PMID- 10970848
TI  - The Drosophila cyclin D-Cdk4 complex promotes cellular growth.
AB  - Mammalian cyclin D-Cdk4 complexes have been characterized as growth factor
      responsive cell cycle regulators. Their levels rise upon growth factor
      stimulation, and they can phosphorylate and thus neutralize Retinoblastoma (Rb)
      family proteins to promote an E2F-dependent transcriptional program and S-phase
      entry. Here we characterize the in vivo function of Drosophila Cyclin D (CycD).
      We find that Drosophila CycD-Cdk4 does not act as a direct G(1)/S-phase
      regulator, but instead promotes cellular growth (accumulation of mass). The
      cellular response to CycD-Cdk4-driven growth varied according to cell type. In
      undifferentiated proliferating wing imaginal cells, CycD-Cdk4 caused accelerated
      cell division (hyperplasia) without affecting cell cycle phasing or cell size. In
      endoreplicating salivary gland cells, CycD-Cdk4 caused excessive DNA replication
      and cell enlargement (hypertrophy). In differentiating eyes, CycD-Cdk4 caused
      cell enlargement (hypertrophy) in post-mitotic cells. Interaction tests with a
      Drosophila Rb homolog, RBF, indicate that CycD-Cdk4 can counteract the cell cycle
      suppressive effects of RBF, but that its growth promoting activity is mediated at
      least in part via other targets.

PMID- 10970849
TI  - Triphosphate structure of guanylate-binding protein 1 and implications for
      nucleotide binding and GTPase mechanism.
AB  - The interferon-gamma-induced guanylate-binding protein 1 (GBP1) belongs to a
      special class of large GTP- binding proteins of 60-100 kDa with unique
      characteristics. Here we present the structure of human GBP1 in complex with the
      non-hydrolysable GTP analogue GppNHp. Basic features of guanine nucleotide
      binding, such as the P-loop orientation and the Mg(2+) co-ordination, are
      analogous to those of Ras-related and heterotrimeric GTP-binding proteins.
      However, the glycosidic bond and thus the orientation of the guanine base and its
      interaction with the protein are very different. Furthermore, two unique regions
      around the base and the phosphate-binding areas, the guanine and the phosphate
      caps, respectively, give the nucleotide-binding site a unique appearance not
      found in the canonical GTP-binding proteins. The phosphate cap, which constitutes
      the region analogous to switch I, completely shields the phosphate-binding site
      from solvent such that a potential GTPase-activating protein cannot approach.
      This has consequences for the GTPase mechanism of hGBP1 and possibly of other
      large GTP-binding proteins.

PMID- 10970850
TI  - Ezrin function is required for ROCK-mediated fibroblast transformation by the Net
      and Dbl oncogenes.
AB  - The small G protein RhoA and its GDP/GTP exchange factors (GEFs) Net and Dbl can
      transform NIH 3T3 fibroblasts, dependent on the activity of the RhoA effector
      kinase ROCK. We investigated the role of the cytoskeletal linker protein ezrin in
      this process. RhoA effector loop mutants which can bind ROCK induce
      relocalization of ezrin to dorsal actin-containing cell surface protrusions, as
      do Net and Dbl. Both processes are inhibited by the ROCK inhibitor Y27632, which
      also inhibits association of ezrin with the cytoskeleton, and phosphorylation of
      T567, conserved between ezrin and its relatives radixin and moesin. ROCK can
      phosphorylate the ezrin C-terminus in vitro. The ezrin mutant T567A cannot be
      relocalized by activated RhoA, Net or Dbl or by ROCK itself, and also inhibits
      RhoA-mediated contractility and focal adhesion formation. Moreover, ezrin T567A,
      but not wild-type ezrin, restores contact inhibition to Net- and Dbl-transformed
      cells, and inhibits the activity of Net and Ras in focus formation assays. These
      results implicate ROCK-mediated ezrin C-terminal phosphorylation in
      transformation by RhoGEFs.

PMID- 10970851
TI  - Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells.
AB  - Phosphatidylinositol 3-kinase (PI3K) regulates several vital cellular processes,
      including signal transduction and membrane trafficking. In order to study the
      intracellular localization of the PI3K product, phosphatidylinositol 3-phosphate
      [PI(3)P], we constructed a probe consisting of two PI(3)P-binding FYVE domains.
      The probe was found to bind specifically, and with high affinity, to PI(3)P both
      in vitro and in vivo. When expressed in fibroblasts, a tagged probe localized to
      endosomes, as detected by fluorescence microscopy. Electron microscopy of
      untransfected fibroblasts showed that PI(3)P is highly enriched on early
      endosomes and in the internal vesicles of multivesicular endosomes. While yeast
      cells deficient in PI3K activity (vps15 and vps34 mutants) were not labelled,
      PI(3)P was found on intralumenal vesicles of endosomes and vacuoles of wild-type
      yeast. vps27Delta yeast cells, which have impaired endosome to vacuole
      trafficking, showed a decreased vacuolar labelling and increased endosome
      labelling. Thus PI(3)P follows a conserved intralumenal degradation pathway, and
      its generation, accessibility and turnover are likely to play a crucial role in
      defining the early endosome and the subsequent steps leading to multivesicular
      endosome formation.

PMID- 10970852
TI  - Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated
      multi-kinase scaffold.
AB  - WAVE proteins are members of the Wiskott-Aldrich syndrome protein (WASP) family
      of scaffolding proteins that coordinate actin reorganization by coupling Rho
      related small molecular weight GTPases to the mobilization of the Arp2/3 complex.
      We identified WAVE-1 in a screen for rat brain A kinase-anchoring proteins
      (AKAPs), which bind to the SH3 domain of the Abelson tyrosine kinase (Abl).
      Recombinant WAVE-1 interacts with cAMP-dependent protein kinase (PKA) and Abl
      kinases when expressed in HEK-293 cells, and both enzymes co-purify with
      endogenous WAVE from brain extracts. Mapping studies have defined binding sites
      for each kinase. Competition experiments suggest that the PKA-WAVE-1 interaction
      may be regulated by actin as the kinase binds to a site overlapping a verprolin
      homology region, which has been shown to interact with actin. Immunocytochemical
      analyses in Swiss 3T3 fibroblasts suggest that the WAVE-1 kinase scaffold is
      assembled dynamically as WAVE, PKA and Abl translocate to sites of actin
      reorganization in response to platelet-derived growth factor treatment. Thus, we
      propose a previously unrecognized function for WAVE-1 as an actin-associated
      scaffolding protein that recruits PKA and Abl.

PMID- 10970853
TI  - Fine tuning bacterial chemotaxis: analysis of Rhodobacter sphaeroides behaviour
      under aerobic and anaerobic conditions by mutation of the major chemotaxis
      operons and cheY genes.
AB  - Rhodobacter sphaeroides chemotaxis is significantly more complex than that of
      enteric bacteria. Rhodobacter sphaeroides has multiple copies of chemotaxis genes
      (two cheA, one cheB, two cheR, three cheW, five cheY but no cheZ), controlling a
      single 'stop-start' flagellum. The growth environment controls the level of
      expression of different groups of genes. Tethered cell analysis of mutants
      suggests that CheY(4) and CheY(5) are the motor-binding response regulators. The
      histidine protein kinase CheA(2) mediates an attractant ('normal') response via
      CheY(4), while CheA(1) and CheY(5) appear to mediate a repellent ('inverted')
      response. CheY(3) facilitates signal termination, possibly acting as a phosphate
      sink, although CheY(1) and CheY(2) can substitute. The normal and inverted
      responses may be initiated by separate sets of chemoreceptors with their relative
      strength dependent on growth conditions. Rhodobacter sphaeroides may use
      antagonistic responses through two chemosensory pathways, expressed at different
      levels in different environments, to maintain their position in a currently
      optimum environment. Complex chemotaxis systems are increasingly being identified
      and the strategy adopted by R.sphaeroides may be common in the bacterial kingdom.

PMID- 10970854
TI  - Src-mediated activation of alpha-diacylglycerol kinase is required for hepatocyte
      growth factor-induced cell motility.
AB  - Diacylglycerol kinases are involved in cell signaling, either as regulators of
      diacylglycerol levels or as intracellular signal-generating enzymes. However,
      neither their role in signal transduction nor their biochemical regulation has
      been elucidated. Hepatocyte growth factor (HGF), upon binding to its tyrosine
      kinase receptor, activates multiple signaling pathways stimulating cell motility,
      scattering, proliferation and branching morphogenesis. Herein we demonstrate
      that: (i) the enzymatic activity of alpha-diacylglycerol kinase (alphaDgk) is
      stimulated by HGF in epithelial, endothelial and alphaDgk-transfected COS cells;
      (ii) cellular expression of an alphaDgk kinase-defective mutant inhibits
      activation of endogenous alphaDgk acting as dominant negative; (iii) specific
      inhibition of alphaDgk prevents HGF-induced cell movement of endothelial cells;
      (iv) HGF induces the association of alphaDgk in a complex with Src, whose
      tyrosine kinase activity is required for alphaDgk activation by HGF; (v) Src wild
      type stimulates alphaDgk activity in vitro; and (vi) alphaDgk can be tyrosine
      phosphorylated in intact cells.

PMID- 10970855
TI  - Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation
      of the Hog1 MAPK pathway.
AB  - The adaptive response to hyperosmotic stress in yeast, termed the high osmolarity
      glycerol (HOG) response, is mediated by two independent upstream pathways that
      converge on the Pbs2 MAP kinase kinase (MAPKK), leading to the activation of the
      Hog1 MAP kinase. One branch is dependent on the Sho1 transmembrane protein, whose
      primary role was found to be the binding and translocation of the Pbs2 MAPKK to
      the plasma membrane, and specifically to sites of polarized growth. The yeast PAK
      homolog Ste20 is essential for the Sho1-dependent activation of the Hog1 MAP
      kinase in response to severe osmotic stress. This function of Ste20 in the HOG
      pathway requires binding of the small GTPase Cdc42. Overexpression of Cdc42
      partially complements the osmosensitivity of ste20Delta mutants, perhaps by
      activating another PAK-like kinase, while a dominant-negative Cdc42 mutant
      inhibited signaling through the SHO1 branch of the HOG pathway. Since activated
      Cdc42 translocates Ste20 to sites of polarized growth, the upstream and
      downstream elements of the HOG pathway are brought together through the membrane
      targeting function of Sho1 and Cdc42.

PMID- 10970856
TI  - Extracellular domains drive homo- but not hetero-dimerization of erbB receptors.
AB  - Many different growth factor ligands, including epidermal growth factor (EGF) and
      the neuregulins (NRGs), regulate members of the erbB/HER family of receptor
      tyrosine kinases. These growth factors induce erbB receptor oligomerization, and
      their biological specificity is thought to be defined by the combination of homo-
      and hetero-oligomers that they stabilize upon binding. One model proposed for
      ligand-induced erbB receptor hetero-oligomerization involves simple
      heterodimerization; another suggests that higher order hetero-oligomers are
      'nucleated' by ligand-induced homodimers. To distinguish between these
      possibilities, we compared the abilities of EGF and NRG1-beta1 to induce homo-
      and hetero-oligomerization of purified erbB receptor extracellular domains. EGF
      and NRG1-beta1 induced efficient homo-oligomerization of the erbB1 and erbB4
      extracellular domains, respectively. In contrast, ligand-induced erbB receptor
      extracellular domain hetero-oligomers did not form (except for s-erbB2-s-erbB4
      hetero-oligomers). Our findings argue that erbB receptor extracellular domains do
      not recapitulate most heteromeric interactions of the erbB receptors, yet
      reproduce their ligand-induced homo-oligomerization properties very well. This
      suggests that mechanisms for homo- and hetero-oligomerization of erbB receptors
      are different, and contradicts the simple heterodimerization hypothesis
      prevailing in the literature.

PMID- 10970857
TI  - Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck
      mice.
AB  - The CD45 tyrosine phosphatase lowers T-cell antigen receptor signalling
      thresholds by its positive actions on p56(lck) tyrosine kinase function. We now
      show that mice expressing active lck(F505) at non-oncogenic levels develop
      aggressive thymic lymphomas on a CD45(-/-) background. CD45 suppresses the
      tumorigenic potential of the kinase by dephosphorylation of the Tyr394
      autophosphorylation site. In CD45(-/-) thymocytes the kinase is switched to a
      hyperactive oncogenic state, resulting in increased resistance to apoptosis.
      Transformation occurs in early CD4(-)CD8(-) thymocytes during the process of TCR
      beta chain rearrangement by a recombinase-independent mechanism. Our findings
      represent the first example in which a tyrosine phosphatase in situ prevents the
      oncogenic actions of a SRC: family tyrosine kinase.

PMID- 10970858
TI  - Chromatin-related properties of CBP fused to MLL generate a myelodysplastic-like
      syndrome that evolves into myeloid leukemia.
AB  - As a result of the recurring translocation t(11;16) (q23;p13.3), MLL (mixed
      lineage leukemia) is fused in frame to CBP (CREB binding protein). This
      translocation has been documented almost exclusively in cases of acute leukemia
      or myelodysplasia secondary to therapy with drugs that target DNA topo isomerase
      II. The minimal chimeric protein that is produced fuses MLL to the bromodomain,
      histone acetyltransferase (HAT) domain, EIA-binding domain and steroid-receptor
      coactivator binding domains of CBP. We show that transplantation of bone marrow
      retrovirally transduced with MLL-CBP induces myeloid leukemias in mice that are
      preceded by a long preleukemic phase similar to the myelodysplastic syndrome
      (MDS) seen in many t(11;16) patients but unusual for other MLL translocations.
      Structure-function analysis demonstrated that fusion of both the bromodomain and
      HAT domain of CBP to the amino portion of MLL is required for full in vitro
      transformation and is sufficient to induce the leukemic phenotype in vivo. This
      suggests that the leukemic effect of MLL-CBP results from the fusion of the
      chromatin association and modifying activities of CBP with the DNA binding
      activities of MLL.

PMID- 10970859
TI  - Inhibition of the mammalian transcription factor LSF induces S-phase-dependent
      apoptosis by downregulating thymidylate synthase expression.
AB  - The thymidylate synthase (TS) gene, which is induced at the G(1)-S transition in
      growth-stimulated cells, encodes an enzyme that is essential for DNA replication
      and cell survival. Here we demonstrate that LSF (LBP-1c, CP2) binds to sites
      within the TS promoter and intronic regions that are required for this induction.
      Mutation of the LSF binding sites inhibits G(1)-S induction of mRNA derived from
      a TS minigene. Furthermore, expression of dominant-negative LSF (LSFdn) prevents
      the increase in TS enzyme levels during G(1)-S, and induces apoptosis in growth-
      stimulated mouse and human cell lines. Such apoptosis can be prevented either by
      circumventing the TS requirement through addition of low concentrations of
      thymidine, or by coexpression of the TS gene driven by a heterologous promoter.
      Induction of apoptosis by LSFdn parallels the process known as thymineless death,
      which is induced by the TS inhibitor and chemotherapeutic drug 5
      fluorodeoxyuridine. Thus, LSF is a novel regulatory factor that supports
      progression through S-phase by targeting a single gene that is critical for cell
      survival.

PMID- 10970860
TI  - Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid
      organs.
AB  - Acetylation of a transcription factor has recently been shown to play a
      significant role in gene regulation. Here we show that GATA-3 is acetylated in T
      cells and that a mutation introduced into amino acids 305-307 (KRR-GATA3) creates
      local hypoacetylation in GATA-3. Remarkably, KRR-GATA3 possesses the most potent
      suppressive effect when compared with other mutants that are disrupted in
      putative acetylation targets. Expressing this mutant in peripheral T cells
      results in defective T-cell homing to systemic lymphnodes, and prolonged T-cell
      survival after activation. These findings have significant implications in that
      the acetylation state of GATA-3 affects its physiological function in the immune
      system and, more importantly, provides evidence for the novel role of GATA-3 in T
      cell survival and homing to secondary lymphoid organs.

PMID- 10970861
TI  - Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha)
      that is encoded by distinct transcripts and that is able to repress hER-alpha
      activation function 1.
AB  - A new isoform of the human estrogen receptor-alpha (hER-alpha) has been
      identified and characterized. This 46 kDa isoform (hERalpha46) lacks the N
      terminal 173 amino acids present in the previously characterized 66 kDa isoform
      (hERalpha66). hERalpha46 is encoded by a new class of hER-alpha transcript that
      lacks the first coding exon (exon 1A) of the ER-alpha gene. We demonstrated that
      these Delta1A hER-alpha transcripts originate from the E and F hER-alpha
      promoters and are produced by the splicing of exon 1E directly to exon 2.
      Functional analysis of hERalpha46 showed that, in a cell context sensitive to the
      transactivation function AF-2, this receptor is an effective ligand-inducible
      transcription factor. In contrast, hERalpha46 is a powerful inhibitor of
      hERalpha66 in a cell context where the transactivating function of AF-1
      predominates over AF-2. The mechanisms by which the AF-1 dominant-negative action
      is exerted may involve heterodimeri zation of the two receptor isoforms and/or
      direct competition for the ER-alpha DNA-binding site. hERalpha66/hERalpha46
      ratios change with the cell growth status of the breast carcinoma cell line MCF7,
      suggesting a role of hERalpha46 in cellular proliferation.

PMID- 10970862
TI  - Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a
      cytoplasmic virus.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP A1) is involved in pre-mRNA
      splicing in the nucleus and translational regulation in the cytoplasm. In the
      present study, we demonstrate that hnRNP A1 also participates in the
      transcription and replication of a cytoplasmic RNA virus, mouse hepatitis virus
      (MHV). Overexpression of hnRNP A1 accelerated the kinetics of viral RNA
      synthesis, whereas the expression in the cytoplasm of a dominant-negative hnRNP
      A1 mutant that lacks the nuclear transport domain significantly delayed it. The
      hnRNP A1 mutant caused a global inhibition of viral mRNA transcription and
      genomic replication, and also a preferential inhibition of the replication of
      defective-interfering RNAs. Similar to the wild-type hnRNP A1, the hnRNP A1
      mutant complexed with an MHV polymerase gene product, the nucleocapsid protein
      and the viral RNA. However, in contrast to the wild-type hnRNP A1, the mutant
      protein failed to bind a 250 kDa cellular protein, suggesting that the
      recruitment of cellular proteins by hnRNP A1 is important for MHV RNA synthesis.
      Our findings establish the importance of cellular factors in viral RNA-dependent
      RNA synthesis.

PMID- 10970863
TI  - Cotranslational dimerization of the Rel homology domain of NF-kappaB1 generates
      p50-p105 heterodimers and is required for effective p50 production.
AB  - Generation of the NF-kappaB p50 transcription factor is mediated by the
      proteasome. We found previously that p50 is generated during translation of the
      NFKB1 gene and that this cotranslational processing allows the production of both
      p50 and p105 from a single mRNA. We now demonstrate that the Rel homology domain
      in p50 undergoes cotranslational dimerization and that this interaction is
      required for efficient production of p50. We further show that this coupling of
      dimerization and proteasome processing during translation uniquely generates p50
      p105 heterodimers. Accordingly, after the primary cotranslational event,
      additional posttranslational steps regulate p50 homodimer formation and the
      intracellular ratio of p50 and p105. This cellular strategy places p50 under the
      control of the p105 inhibitor early in its biogenesis, thereby regulating the
      pool of p50 homodimers within the cell.

PMID- 10970864
TI  - Multiple portions of poly(A)-binding protein stimulate translation in vivo.
AB  - Translational stimulation of mRNAs during early development is often accompanied
      by increases in poly(A) tail length. Poly(A)-binding protein (PAB) is an
      evolutionarily conserved protein that binds to the poly(A) tails of eukaryotic
      mRNAs. We examined PAB's role in living cells, using both Xenopus laevis oocytes
      and Saccharomyces cerevisiae, by tethering it to the 3'-untranslated region of
      reporter mRNAs. Tethered PAB stimulates translation in vivo. Neither a poly(A)
      tail nor PAB's poly(A)-binding activity is required. Multiple domains of PAB act
      redundantly in oocytes to stimulate translation: the interaction of RNA
      recognition motifs (RRMs) 1 and 2 with eukaryotic initiation factor-4G correlates
      with translational stimulation. Interaction with Paip-1 is insufficient for
      stimulation. RRMs 3 and 4 also stimulate, but bind neither factor. The regions of
      tethered PAB required in yeast to stimulate translation and stabilize mRNAs
      differ, implying that the two functions are distinct. Our results establish that
      oocytes contain the machinery necessary to support PAB-mediated translation and
      suggest that PAB may be an important participant in translational regulation
      during early development.

PMID- 10970865
TI  - Nonsense-mediated decay of glutathione peroxidase 1 mRNA in the cytoplasm depends
      on intron position.
AB  - mRNA for glutathione peroxidase 1 (GPx1) is subject to cytoplasmic nonsense
      mediated decay (NMD) when the UGA selenocysteine (Sec) codon is recognized as
      nonsense. Here, we demonstrate by moving the sole intron of the GPx1 gene that
      either the Sec codon or a TAA codon in its place elicits NMD when located >/=59
      bp but not </=43 bp upstream of the intron. Therefore, the exon-exon junction of
      GPx1 mRNA positions the boundary between nonsense codons that do and do not
      elicit NMD, as has been shown for the 3'-most junctions of mRNAs subject to
      nucleus-associated NMD. We also demonstrate by using a regulatable promoter to
      drive GPx1 gene expression that cytoplasmic NMD is characteristic of steady-state
      mRNA, in contrast to nucleus-associated NMD. These findings clarify the
      mechanistic relationship between cytoplasmic and nucleus-associated NMD and offer
      the first demonstration that nuclear introns can influence cytoplasmic NMD.
      Finally, by analyzing hybrid GPx1 genes, we disprove the idea that the cellular
      site of NMD is determined by the efficiency of translation initiation.

PMID- 10970866
TI  - Crystal structure of a eukaryote/archaeon-like protyl-tRNA synthetase and its
      complex with tRNAPro(CGG).
AB  - Prolyl-tRNA synthetase (ProRS) is a class IIa synthetase that, according to
      sequence analysis, occurs in different organisms with one of two quite distinct
      structural architectures: prokaryote-like and eukaryote/archaeon-like. The
      primary sequence of ProRS from the hypothermophilic eubacterium Thermus
      thermophilus (ProRSTT) shows that this enzyme is surprisingly eukaryote/archaeon
      like. We describe its crystal structure at 2.43 angstom resolution, which reveals
      a feature that is unique among class II synthetases. This is an additional zinc
      containing domain after the expected class IIa anticodon-binding domain and whose
      C-terminal extremity, which ends in an absolutely conserved tyrosine, folds back
      into the active site. We also present an improved structure of ProRSTT complexed
      with tRNAPro(CGG) at 2.85 angstom resolution. This structure represents an
      initial docking state of the tRNA in which the anticodon stem-loop is engaged,
      particularly via the tRNAPro-specific bases G35 and G36, but the 3' end does not
      enter the active site. Considerable structural changes in tRNA and/or synthetase,
      which are probably induced by small substrates, are required to achieve the
      conformation active for aminoacylation.

PMID- 10970867
TI  - Regulation of the 26S proteasome by adenovirus E1A.
AB  - We have identified the N-terminus of adenovirus early region 1A (AdE1A) as a
      region that can regulate the 26S proteasome. Specifically, in vitro and in vivo
      co-precipitation studies have revealed that the 19S regulatory components of the
      proteasome, Sug1 (S8) and S4, bind through amino acids (aa) 4-25 of Ad5 E1A. In
      vivo expression of wild-type (wt) AdE1A, in contrast to the N-terminal AdE1A
      mutant that does not bind the proteasome, reduces ATPase activity associated with
      anti-S4 immunoprecipitates relative to mock-infected cells. This reduction in
      ATPase activity correlates positively with the ability of wt AdE1A, but not the N
      terminal deletion mutant, to significantly reduce the ability of HPV16 E6 to
      target p53 for ubiquitin-mediated proteasomal degradation. AdE1A/proteasomal
      complexes are present in both the cytoplasm and the nucleus, suggesting that
      AdE1A interferes with both nuclear and cytoplasmic proteasomal degradation. We
      have also demonstrated that wt AdE1A and the N-terminal AdE1A deletion mutant are
      substrates for proteasomal-mediated degradation. AdE1A degradation is not,
      however, mediated through ubiquitylation, but is regulated through
      phosphorylation of residues within a C-terminal PEST region (aa 224-238).

PMID- 10970868
TI  - Regulation of origin recognition complex conformation and ATPase activity:
      differential effects of single-stranded and double-stranded DNA binding.
AB  - The Saccharomyces cerevisiae origin recognition complex (ORC) is bound to origins
      of DNA replication throughout the cell cycle and directs the assembly of higher
      order protein-DNA complexes during G(1). To examine the fate of ORC when origin
      DNA is unwound during replication initiation, we determined the effect of single
      stranded DNA (ssDNA) on ORC. We show that ORC can bind ssDNA and that ORC bound
      to ssDNA is distinct from that bound to double-stranded origin DNA. ssDNA
      stimulated ORC ATPase activity, whereas double-stranded origin DNA inhibited the
      same activity. Electron microscopy studies revealed two alternative conformations
      of ORC: an extended conformation stabilized by origin DNA and a bent conformation
      stabilized by ssDNA. Therefore, ORC appears to exist in two distinct states with
      respect to its conformation and ATPase activity. Interestingly, the effect of
      ssDNA on these properties of ORC is correlated with ssDNA length. Since double
      stranded origin DNA and ssDNA differentially stabilize these two forms of ORC, we
      propose that origin unwinding triggers a transition between these alternative
      states.

PMID- 10970869
TI  - Gene expression elicited by NFAT in the presence or absence of cooperative
      recruitment of Fos and Jun.
AB  - Cooperation between nuclear factor of activated T cells (NFAT) and AP-1 (Fos-Jun)
      proteins on composite NFAT-AP-1 DNA elements constitutes a powerful mechanism for
      signal integration of the calcium and protein kinase C/Ras pathways in the
      regulation of gene expression. Here we report that NFAT can induce expression of
      certain genes in T cells without the need for cooperative recruitment of Fos and
      Jun. Using NFAT1 mutant proteins that are unable to interact with Fos-Jun dimers
      but are unaffected in DNA binding or transcriptional activity, we show that
      expression of interleukin (IL)-2, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), IL-3, IL-4, MIP1alpha and Fas ligand mRNAs is absolutely
      dependent on cooperation between NFAT and Fos-Jun; in contrast, NFAT induces
      tumor necrosis factor alpha (TNFalpha) mRNA and IL-13 promoter activity without
      any necessity to recruit Fos and Jun. Furthermore, we show that NFAT-Fos-Jun
      cooperation is also essential to elicit the NFAT-dependent program of activation
      induced cell death. Our results support the hypothesis that even in a single cell
      type, NFAT activation can evoke two distinct biological programs of gene
      expression, dependent or independent of NFAT-AP-1 cooperation.

PMID- 10970870
TI  - Characterization of mSelB, a novel mammalian elongation factor for selenoprotein
      translation.
AB  - Decoding of UGA selenocysteine codons in eubacteria is mediated by the
      specialized elongation factor SelB, which conveys the charged tRNA(Sec) to the A
      site of the ribosome, through binding to the SECIS mRNA hairpin. In an attempt to
      isolate the eukaryotic homolog of SelB, a database search in this work identified
      a mouse expressed sequence tag containing the complete cDNA encoding a novel
      protein of 583 amino acids, which we called mSelB. Several lines of evidence
      enabled us to establish that mSelB is the bona fide mammalian elongation factor
      for selenoprotein translation: it binds GTP, recognizes the Sec-tRNA(Sec) in
      vitro and in vivo, and is required for efficient selenoprotein translation in
      vivo. In contrast to the eubacterial SelB, the recombinant mSelB alone is unable
      to bind specifically the eukaryotic SECIS RNA hairpin. However, complementation
      with HeLa cell extracts led to the formation of a SECIS-dependent complex
      containing mSelB and at least another factor. Therefore, the role carried out by
      a single elongation factor in eubacterial selenoprotein translation is devoted to
      two or more specialized proteins in eukaryotes.

PMID- 10970871
TI  - The Rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in synaptic
      transmission.
AB  - Guanine nucleotide exchange is essential for Rab GTPase activities in regulating
      intracellular vesicle trafficking. This exchange process is facilitated by
      guanine nucleotide exchange factor (GEF). Previously, we identified
      Caenorhabditis elegans AEX-3 as a GEF for Rab3 GTPase. Here we demonstrate that
      AEX-3 regulates neural activities through a second, previously unrecognized
      pathway via interactions with the novel protein CAB-1. CAB-1 is 425 amino acids
      long and has an 80 amino acid motif in common with the mouse neural protein NPDC
      1. cab-1 and rab-3 mutants have different behavioral defects, and RAB-3
      localization and function are apparently normal in cab-1 mutants, indicating that
      the CAB-1 pathway is distinct from the RAB-3 pathway. The aex-3 mutant phenotype
      resembles the sum of the rab-3 and cab-1 mutant phenotypes, indicating that AEX-3
      regulates two different pathways for neural activities. We propose that
      connection of multiple pathways may be an important feature of Rab GEFs to
      coordinate various cellular events.

PMID- 10970873
TI  - Neuralized functions cell autonomously to regulate Drosophila sense organ
      development.
AB  - Neurogenic genes, including Notch and Delta, are thought to play important roles
      in regulating cell-cell interactions required for Drosophila sense organ
      development. To define the requirement of the neurogenic gene neuralized (neu) in
      this process, two independent neu alleles were used to generate mutant clones. We
      find that neu is required for determination of cell fates within the proneural
      cluster and that cells mutant for neu autonomously adopt neural fates when
      adjacent to wild-type cells. Furthermore, neu is required within the sense organ
      lineage to determine the fates of daughter cells and accessory cells. To gain
      insight into the mechanism by which neu functions, we used the GAL4/UAS system to
      express wild-type and epitope-tagged neu constructs. We show that Neu protein is
      localized primarily at the plasma membrane. We propose that the function of neu
      in sense organ development is to affect the ability of cells to receive Notch
      Delta signals and thus modulate neurogenic activity that allows for the
      specification of non-neuronal cell fates in the sense organ.

PMID- 10970872
TI  - Urokinase-type plasminogen activator and its receptor synergize to promote
      pathogenic proteolysis.
AB  - Urokinase-type plasminogen activator (uPA) is a potent catalyst of extracellular
      proteolysis, which also binds to a high-affinity plasma membrane receptor (uPAR).
      Binding of uPA may influence pericellular proteolysis and/or activate
      intracellular signal transduction. Transgenic mice overexpressing either uPA or
      uPAR in basal epidermis and hair follicles had no detectable cutaneous
      alterations. In contrast, bi-transgenic mice overexpressing both uPA and uPAR,
      obtained by crossing the two transgenic lines, developed extensive alopecia
      induced by involution of hair follicles, epidermal thickening and sub-epidermal
      blisters. The phenotype was due to uPA catalytic activity since combined
      overexpression of uPAR and uPAR-binding but catalytically inactive uPA in the
      same tissue was not detrimental in another bi-transgenic line. It was accompanied
      by increased plasmin-generating capacity, up-regulation and activation of matrix
      metalloproteinases type-2 and -9, and cleavage of uPAR. Thus, combined
      overexpression of uPA and uPAR acts in synergy to promote pathogenic
      extracellular proteolysis.

PMID- 10970874
TI  - Structure of the ArsA ATPase: the catalytic subunit of a heavy metal resistance
      pump.
AB  - Active extrusion is a common mechanism underlying detoxification of heavy metals,
      drugs and antibiotics in bacteria, protozoa and mammals. In Escherichia coli, the
      ArsAB pump provides resistance to arsenite and antimonite. This pump consists of
      a soluble ATPase (ArsA) and a membrane channel (ArsB). ArsA contains two
      nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony.
      Binding of metalloids stimulates ATPase activity. The crystal structure of ArsA
      reveals that both NBSs and the metal-binding site are located at the interface
      between two homologous domains. A short stretch of residues connecting the metal
      binding site to the NBSs provides a signal transduction pathway that conveys
      information on metal occupancy to the ATP hydrolysis sites. Based on these
      structural features, we propose that the metal-binding site is involved directly
      in the process of vectorial translocation of arsenite or antimonite across the
      membrane. The relative positions of the NBS and the inferred mechanism of
      allosteric activation of ArsA provide a useful model for the interaction of the
      catalytic domains in other transport ATPases.

PMID- 10970875
TI  - Ca(2+) signalling is not required for chemotaxis in Dictyostelium.
AB  - Dictyostelium cells can move rapidly towards a source of cyclic-AMP (cAMP). This
      chemoattractant is detected by G-protein-linked receptors, which trigger a
      signalling cascade including a rapid influx of Ca(2+). We have disrupted an
      inositol 1,4,5-trisphosphate (InsP(3)) receptor-like gene, iplA, to produce null
      cells in which Ca(2+) entry in response to chemoattractants is abolished, as is
      the normal increase in free cytosolic Ca(2+) ([Ca(2+)](c)) that follows
      chemotactic stimulation. However, the resting [Ca(2+)](c) is similar to wild
      type. This mutant provides a test for the role of Ca(2+) influx in both
      chemotaxis and the signalling cascade that controls it. The production of cyclic
      GMP and cAMP, and the activation of the MAP kinase, DdERK2, triggered from the
      cAMP receptor, are little perturbed in the mutant; mobilization of actin into the
      cytoskeleton also follows similar kinetics to wild type. Mutant cells chemotax
      efficiently towards cAMP or folic acid and their sensitivity to cAMP is similar
      to wild type. Finally, they move at similar speeds to wild-type cells, with or
      without chemoattractant. We conclude that Ca(2+) signalling is not necessary for
      chemotaxis to cAMP.

PMID- 10970876
TI  - Matrix metalloproteinases: effectors of development and normal physiology.

PMID- 10970877
TI  - Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor
      neuron and ventral interneuron fates.
AB  - There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral
      neuronal fate in the vertebrate central nervous system through Nkx-class
      homeodomain proteins. We have examined the patterns of neurogenesis in mice
      carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral
      switch in the identity of progenitors and in the fate of postmitotic neurons. At
      many axial levels there is a complete block in the generation of V2 interneurons
      and motor neurons and a compensatory ventral expansion in the domain of
      generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in
      regional patterning and neuronal fate determination.

PMID- 10970878
TI  - Single mesodermal cells guide outgrowth of ectodermal tubular structures in
      Drosophila.
AB  - The Drosophila tracheal system, a tubular network, is formed from isolated
      ectodermal metameres by guided branch outgrowth and branch fusion. Branch
      outgrowth is triggered by the localized and transient activity of Branchless
      (Bnl/dFGF). Here, we report the discovery of a mesodermal cell that links the
      leading cells of outgrowing main branches 2.5 hr before they fuse. This bridge
      cell serves as an essential guidance post and needs Hunchback (Hb) activity to
      exert its function. The bridge-cell provides cues acting in concert with Bnl/dFGF
      signaling to mediate directed branch outgrowth that ultimately leads to position
      specific branch fusion.

PMID- 10970879
TI  - Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding.
AB  - Ikaros is a sequence-specific DNA-binding protein that is essential for
      lymphocyte development. Little is known about the molecular function of Ikaros,
      although recent results have led to the hypothesis that it recruits genes
      destined for heritable inactivation to foci containing pericentromeric
      heterochromatin. To gain further insight into the functions of Ikaros, we have
      examined the mechanism by which it is targeted to centromeric foci. Efficient
      targeting of Ikaros was observed upon ectopic expression in 3T3 fibroblasts,
      demonstrating that lymphocyte-specific proteins and a lymphoid nuclear
      architecture are not required. Pericentromeric targeting did not result from an
      interaction with the Mi-2 remodeling factor, as only a small percentage of Mi-2
      localized to centromeric foci in 3T3 cells. Rather, targeting was dependent on
      the amino-terminal DNA-binding zinc finger domain and carboxy-terminal
      dimerization domain of Ikaros. The carboxy-terminal domain was required only for
      homodimerization, as targeting was restored when this domain was replaced with a
      leucine zipper. Surprisingly, a detailed substitution mutant analysis of the
      amino-terminal domain revealed a close correlation between DNA-binding and
      pericentromeric targeting. These results show that DNA binding is essential for
      the pericentromeric localization of Ikaros, perhaps consistent with the presence
      of Ikaros binding sites within centromeric DNA repeats. Models for the function
      of Ikaros that are consistent with this targeting mechanism are discussed.

PMID- 10970880
TI  - A C. elegans mediator protein confers regulatory selectivity on lineage-specific
      expression of a transcription factor gene.
AB  - The Caenorhabditis elegans caudal homolog, pal-1, is required for neurogenesis in
      the male tail. We show that expression of pal-1 in the postembryonic neuroblast
      cell V6 can be initiated by two alternate pathways. One pathway, acting in wild
      type, requires a regulatory element in the fifth pal-1 intron. The other pathway,
      independent of this element, is normally repressed by the newly identified gene
      sop-1, which encodes a homolog of the mammalian Mediator complex protein TRAP230.
      In sop-1 mutants, pal-1 is activated by a pathway that is stimulated by bar
      1/beta-catenin, a component of the Wnt signal transduction pathway. The results
      support a physiological role of the Mediator complex in conveying regulatory
      signals to the transcriptional apparatus.

PMID- 10970881
TI  - Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA
      surveillance in C. elegans.
AB  - Messenger RNA surveillance, the selective and rapid degradation of mRNAs
      containing premature stop codons, occurs in all eukaryotes tested. The biological
      role of this decay pathway, however, is not well understood. To identify natural
      substrates of mRNA surveillance, we used a cDNA-based representational difference
      analysis to identify mRNAs whose abundance increases in Caenorhabditis elegans
      smg(-) mutants, which are deficient for mRNA surveillance. Alternatively spliced
      mRNAs of genes encoding ribosomal proteins L3, L7a, L10a, and L12 are abundant
      natural targets of mRNA surveillance. Each of these genes expresses two distinct
      mRNAs. A productively spliced mRNA, whose abundance does not change in smg(-)
      mutants, encodes a normal, full-length, ribosomal protein. An unproductively
      spliced mRNA, whose abundance increases dramatically in smg(-) mutants, contains
      premature stop codons because of incomplete removal of an alternatively spliced
      intron. In transgenic animals expressing elevated quantities of RPL-12, a greater
      proportion of endogenous rpl-12 transcript is spliced unproductively. Thus, RPL
      12 appears to autoregulate its own splicing, with unproductively spliced mRNAs
      being degraded by mRNA surveillance. We demonstrate further that alternative
      splicing of rpl introns is conserved among widely diverged nematodes. Our results
      suggest that one important role of mRNA surveillance is to eliminate unproductive
      by-products of gene regulation.

PMID- 10970882
TI  - Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell
      cycle progression.
AB  - The c-Myc oncoprotein plays an important role in the growth and proliferation of
      normal and neoplastic cells. To execute these actions, c-Myc is thought to
      regulate functionally diverse sets of genes that directly govern cellular mass
      and progression through critical cell cycle transitions. Here, we provide several
      lines of evidence that c-Myc promotes ubiquitin-dependent proteolysis by directly
      activating expression of the Cul1 gene, encoding a critical component of the
      ubiquitin ligase SCF(SKP2). The cell cycle inhibitor p27(kip1) is a known target
      of the SCF(SKP2) complex, and Myc-induced Cul1 expression matched well with the
      kinetics of declining p27(kip1) protein. Enforced Cul1 expression or antisense
      neutralization of p27(kip1) was capable of overcoming the slow-growth phenotype
      of c-Myc null primary mouse embryonic fibroblasts (MEFs). In reconstitution
      assays, the addition of in vitro translated Cul1 protein alone was able to
      restore p27(kip1) ubiquitination and degradation in lysates derived from c-myc(-/
      ) MEFs or density-arrested human fibroblasts. These functional and biochemical
      data provide a direct link between c-Myc transcriptional regulation and ubiquitin
      mediated proteolysis and together support the view that c-Myc promotes G(1) exit
      in part via Cul1-dependent ubiquitination and degradation of the CDK inhibitor,
      p27(kip1).

PMID- 10970883
TI  - Degradation of Drosophila PIM regulates sister chromatid separation during
      mitosis.
AB  - Drosophila Pimples (PIM) and Three rows (THR) are required for sister chromatid
      separation in mitosis. PIM accumulates during interphase and is degraded rapidly
      during mitosis. This degradation is dependent on a destruction box similar to
      that of B-type cyclins. Nondegradable PIM with a mutant destruction box can
      rescue sister chromatid separation in pim mutants but only when expressed at low
      levels. Higher levels of nondegradable PIM, as well as overexpression of wild
      type PIM, inhibit sister chromatid separation. Moreover, cells arrested in
      mitosis before sister chromatid separation (by colcemid or by mutations in
      fizzy/CDC20) fail to degrade PIM. Thus, although not related by primary sequence,
      PIM has intriguing functional similarities to the securin proteins of budding
      yeast, fission yeast, and vertebrates. Whereas these securins are known to form a
      complex with separins, we show that PIM associates in vivo with THR, which does
      not contain the conserved separin domain.

PMID- 10970884
TI  - Promotion of Rad51-dependent D-loop formation by yeast recombination factor
      Rdh54/Tid1.
AB  - The first DNA joint formed in homologous recombination processes is a D-loop.
      Saccharomyces cerevisiae RDH54/TID1-encoded product, a Swi2/Snf2-like factor
      involved in recombination, is shown here to promote D-loop formation with Rad51
      recombinase. Physical interaction between Rdh54 and Rad51 is functionally
      important because Rdh54 does not enhance the recombinase activity of the
      Escherichia coli RecA protein. Robust dsDNA-activated ATPase activity in Rdh54
      generates unconstrained negative and positive supercoils in DNA. Efficient D-loop
      formation occurs with even topologically relaxed DNA, suggesting that via
      specific protein-protein interactions, the negative supercoils produced by Rdh54
      are used by Rad51 for making DNA joints.

PMID- 10970885
TI  - Discoidin domain receptor 1 functions in axon extension of cerebellar granule
      neurons.
AB  - In the developing cerebellum, granule neuron axon outgrowth is a key step toward
      establishing proper connections with Purkinje neurons, the principal output
      neuron of the cerebellum. During a search for genes that function in this
      process, we identified a receptor tyrosine kinase discoidin domain receptor 1
      (DDR1) expressed in granule cells throughout their development. Overexpression of
      a dominant-negative form of DDR1 in immature granule cells results in severe
      reduction of neurite outgrowth in vitro, in dissociated primary culture, and in
      vivo, in organotypic slices of neonatal cerebellum. Granule cells that fail to
      extend axons are positive for differentiation markers such as TAG-1 and the
      neuron-specific class III beta-tubulin, suggesting that development is affected
      after granule cells commit to terminal differentiation. DDR1 activation appears
      to be mediated by its ligand, collagen, which is localized to the pial layer of
      the developing cerebellum, thereby leading to granule cell parallel fiber
      extension. Our results therefore indicate that collagen-DDR1 signaling is
      essential for granule neuron axon formation and further suggest a unique role of
      pia in cerebellar cortex histogenesis.

PMID- 10970886
TI  - Structural basis for autorepression of retinoid X receptor by tetramer formation
      and the AF-2 helix.
AB  - The 9-cis-retinoic acid receptors (RXRalpha, RXRbeta, and RXRgamma) are nuclear
      receptors that play key roles in multiple hormone-signaling pathways. Biochemical
      data indicate that, in the absence of ligand, RXR can exist as an inactive
      tetramer and that its dissociation, induced by ligand, is important for receptor
      activation. In this article we report the inactivated tetramer structures of the
      RXRalpha ligand-binding domain (LBD), either in the absence of or in the presence
      of a nonactivating ligand. These structures reveal that the RXR LBD tetramer
      forms a compact, disc-shaped complex, consisting of two symmetric dimers that are
      packed along helices 3 and 11. In each monomer, the AF-2 helix protrudes away
      from the core domain and spans into the coactivator binding site in the adjacent
      monomer of the symmetric dimer. In this configuration, the AF-2 helix physically
      excludes the binding of coactivators and suggests an autorepression mechanism
      that is mediated by the AF-2 helix within the tetramer. The RXR-tetramer
      interface is assembled from amino acids that are conserved across several closely
      related receptors, including the HNF4s and COUP transcription factors, and may
      therefore provide a model for understanding structure and regulation of this
      subfamily of nuclear receptors.

PMID- 10970887
TI  - Promoter opening by sigma(54) and sigma(70) RNA polymerases: sigma factor
      directed alterations in the mechanism and tightness of control.
AB  - Transcription control at the melting step is not yet understood. Here, band
      shift, cross-linking, and transcription experiments on diverse DNA probes were
      used with two bacterial RNA polymerase holoenzymes that differ in how they
      regulate melting. Data indicated that both sigma(54) and sigma(70) holoenzymes
      assume a default closed form that cannot establish single-strand binding. Upon
      activation the enzymes are converted to an open form that can bind simultaneously
      to the upstream fork junction and to the melted transcription start site. The key
      difference is that sigma(54) imposes tighter regulation by creating a complex
      molecular switch at -12/-11; the current data show that this switch can be thrown
      by activator. In this case an ATP-bound enhancer protein causes sigma(54) to
      alter its cross-linking pattern near -11 and also causes a reorganization of
      holoenzyme: DNA interactions, detected by electrophoretic mobility-shift assay.
      At a temperature-dependent sigma(70) promoter, elevated temperature alone can
      assist in triggering conformational changes that enhance the engagement of single
      strand DNA. Thus, the two sigma factors modify the same intrinsic opening pathway
      to create quite different mechanisms of transcriptional regulation.

PMID- 10970888
TI  - KDC1, a novel carrot root hair K+ channel. Cloning, characterization, and
      expression in mammalian cells.
AB  - Potassium is an essential nutrient which plays an important role in many aspects
      of plant growth and development. Plants have developed a number of highly
      specific mechanisms to take up potassium from the soil; these include the
      expression of K(+) transporters and potassium channels in root cells. Despite the
      fact that root epidermal and hair cells are in direct contact with the soil, the
      role of these tissues in K(+) uptake is not well understood. Here we report the
      molecular cloning and functional characterization of a novel potassium channel
      KDC1 which forms part of a new subfamily of plant K(in) channels. Kdc1 was
      isolated from carrot root RNA and in situ hybridization experiments show Kdc1 to
      be highly expressed in root hair cells. Expressing the KDC1 protein in Chinese
      hamster ovary cells identified it as a voltage and pH-dependent inwardly
      rectifying potassium channel. An electrophysiological analysis of carrot root
      hair protoplasts confirmed the biophysical properties of the Kdc1 gene product
      (KDC1) in the heterologous expression system. KDC1 thus represents a major K(+)
      uptake channel in carrot root hair cells.

PMID- 10970889
TI  - FAD insertion is essential for attaining the assembly competence of the
      dihydrolipoamide dehydrogenase (E3) monomer from Escherichia coli.
AB  - Dihydrolipoamide dehydrogenase (E3) from Escherichia coli, an FAD-linked
      homodimer, can be fully reconstituted in vitro following denaturation in 6 m
      guanidinium chloride. Complete restoration of activity occurs within 1-2 h in the
      presence of FAD, dithiothreitol, and bovine serum albumin. In the absence of FAD,
      the dihydrolipoamide dehydrogenase monomer forms a stable folding intermediate,
      which is incapable of dimerization. This intermediate displays a similar tryptic
      resistance to the native enzyme but is less heat-stable, because its ability to
      form native E3 is lost after incubation at 65 degrees C for 15 min. The presence
      of FAD promotes slow, additional conformational rearrangements of the E3 subunit
      as observed by cofactor-dependent decreases in intrinsic tryptophan fluorescence.
      However, after 2 h, the tryptophan fluorescence spectrum and far UV CD spectrum
      of E3, refolded in the absence of FAD, are similar to that of the native enzyme,
      and full activity can still be recovered on addition of FAD. Cross-linking
      studies show that FAD insertion is necessary for the monomeric folding
      intermediate to attain an assembly competent state leading to dimerization. Thus
      cofactor insertion represents a key step in the assembly of this enzyme, although
      its initial presence appears not to be required to promote the correct folding
      pathway.

PMID- 10970890
TI  - Disruption of a single copy of the SERCA2 gene results in altered Ca2+
      homeostasis and cardiomyocyte function.
AB  - A mouse model carrying a null mutation in one copy of the sarcoplasmic reticulum
      (SR) Ca(2+)-ATPase isoform 2 (SERCA2) gene, in which SERCA2 protein levels are
      reduced by approximately 35%, was used to investigate the effects of decreased
      SERCA2 level on intracellular Ca(2+) homeostasis and contractile properties in
      isolated cardiomyocytes. When compared with wild-type controls, SR Ca(2+) stores
      and Ca(2+) release in myocytes of SERCA2 heterozygous mice were decreased by
      approximately 40-60% and approximately 30-40%, respectively, and the rate of
      myocyte shortening and relengthening were each decreased by approximately 40%.
      However, the rate of Ca(2+) transient decline (tau) was not altered
      significantly, suggesting that compensation was occurring in the removal of
      Ca(2+) from the cytosol. Phospholamban, which inhibits SERCA2, was decreased by
      approximately 40% in heterozygous hearts, and basal phosphorylation of Ser-16 and
      Thr-17, which relieves the inhibition, was increased approximately 2- and 2.1
      fold. These results indicate that reduced expression and increased
      phosphorylation of phospholamban provides compensation for decreased SERCA2
      protein levels in heterozygous heart. Furthermore, both expression and current
      density of the sarcolemmal Na(+)-Ca(2+) exchanger were up-regulated. These
      results demonstrate that a decrease in SERCA2 levels can directly modify
      intracellular Ca(2+) homeostasis and myocyte contractility. However, the
      resulting deficit is partially compensated by alterations in phospholamban/SERCA2
      interactions and by up-regulation of the Na(+)-Ca(2+) exchanger.

PMID- 10970891
TI  - Thrombin-activable fibrinolysis inhibitor attenuates (DD)E-mediated stimulation
      of plasminogen activation by reducing the affinity of (DD)E for tissue
      plasminogen activator. A potential mechanism for enhancing the fibrin specificity
      of tissue plasminogen activator.
AB  - A complex of d-dimer noncovalently associated with fragment E ((DD)E), a
      degradation product of cross-linked fibrin that binds tissue plasminogen
      activator (t-PA) and plasminogen (Pg) with affinities similar to those of fibrin,
      compromises the fibrin specificity of t-PA by stimulating systemic Pg activation.
      In this study, we examined the effect of thrombin-activable fibrinolysis
      inhibitor (TAFI), a latent carboxypeptidase B (CPB)-like enzyme, on the
      stimulatory activity of (DD)E. Incubation of (DD)E with activated TAFI (TAFIa) or
      CPB (a) produces a 96% reduction in the capacity of (DD)E to stimulate t-PA
      mediated activation of Glu- or Lys-Pg by reducing k(cat) and increasing K(m) for
      the reaction; (b) induces the release of 8 mol of lysine/mol of (DD)E, although
      most of the stimulatory activity is lost after release of only 4 mol of
      lysine/mol (DD)E; and (c) reduces the affinity of (DD)E for Glu-Pg, Lys-Pg, and t
      PA by 2-, 4-, and 160-fold, respectively. Because TAFIa- or CPB-exposed (DD)E
      produces little stimulation of Glu-Pg activation by t-PA, (DD)E is not degraded
      into fragment E and d-dimer, the latter of which has been reported to impair
      fibrin polymerization. These data suggest a novel role for TAFIa. By attenuating
      systemic Pg activation by (DD)E, TAFIa renders t-PA more fibrin-specific.

PMID- 10970892
TI  - The chaperone protein BiP binds to a mutant prion protein and mediates its
      degradation by the proteasome.
AB  - Familial prion diseases are thought to result from a change in structure of the
      mutant prion protein (PrP), which takes a pathogenic conformation. We have
      examined the role of molecular chaperones in the folding of normal and mutant PrP
      Q217R (PrP(217)) in transfected neuroblastoma cells. In a previous report we
      showed that, although most of the PrP(217) forms escape the endoplasmic reticulum
      quality control system and aggregate in post-Golgi compartments, a significant
      proportion of PrP(217) retains the C-terminal glycosylphosphatidyl inositol
      signal peptide (PrP32), and does not exit the endoplasmic reticulum (Singh, N.,
      Zanusso, G., Chen, S. G., Fujioka, H., Richardson, S., Gambetti, P., and
      Petersen, R. B. (1997) J. Biol. Chem. 272, 28461-28470). We have now studied the
      folding and turnover of PrP32 to understand the mechanism by which abnormal PrP
      forms cause cellular toxicity in our cell culture model and in the human brain
      carrying the Gerstmann-Straussler-Scheinker disease Q217R mutation. In this
      report, we show that PrP32 remains associated with the chaperone BiP for an
      abnormally prolonged period of time and is degraded by the proteasomal pathway.
      This study is the first demonstration that BiP is chaperoning the folding of PrP
      and plays a role in maintaining the quality control in the PrP maturation
      pathway. Our data provide new insight into the diverse pathways of mutant PrP
      metabolism and neurotoxicity.

PMID- 10970893
TI  - Self-association of human apolipoprotein E3 and E4 in the presence and absence of
      phospholipid.
AB  - Human apolipoprotein E (apoE) exists as three main isoforms, differing by single
      amino acid substitutions, with the apoE4 isoform strongly linked to the incidence
      of late onset Alzheimer's disease. We have expressed and purified apoE3 and apoE4
      from Escherichia coli and compared their hydrodynamic properties by gel
      permeation liquid chromatography, capillary electrophoresis, circular dichroism,
      and sedimentation methods. Sedimentation velocity experiments, employing a new
      method for determining the size distribution of polydisperse macromolecules in
      solution (Schuck, P. (2000) Biophys. J. 78, 1606-1619), provide direct evidence
      for the heterogeneous solution structures of apoE3 and apoE4. In a lipid-free
      environment, apoE3 and apoE4 exist as a slow equilibrium mixture of monomer,
      tetramer, octamer, and a small proportion of higher oligomers. Both sedimentation
      velocity and equilibrium experiments indicate that apoE4 has a greater propensity
      to self-associate. We also demonstrate that apoE3 and apoE4 oligomers dissociate
      significantly in the presence of dihexanoylphosphatidylcholine micelles (20 mm)
      and to a lesser extent at submicellar concentrations (4 mm). The alpha-helical
      content for both isoforms was almost identical (50%) in the presence and absence
      of dihexanoylphosphatidylcholine. These results reveal that apoE oligomers
      undergo phospholipid-induced dissociation to folded monomers, suggesting the
      monomeric form prevails on the lipoprotein surface in vivo.

PMID- 10970894
TI  - Do modulators of the mitochondrial K(ATP) channel change the function of
      mitochondria in situ?
AB  - Pharmacological opening of mitochondrial cardiac ATP-sensitive potassium (K(ATP))
      channels has the chance to be a promising but still controversial
      cardioprotective mechanism. Physiological roles of mitochondrial K(ATP) channels
      in the myocardium remain unclear. We studied the effects of diazoxide, a specific
      opener of these channels, on the function of rat mitochondria in situ in saponin
      permeabilized fibers using an ionic medium that mimics the cytosol. In the
      presence of NADH-producing substrates (malate + glutamate), neither 100 microm
      diazoxide nor 100 microm glibenclamide (a K(ATP) channel blocker) changed the
      mitochondrial respiration in the absence or presence of ADP. Because the K(ATP)
      channel function could be modified by changes in adenine nucleotide
      concentrations near the mitochondria, we studied the effects of diazoxide and
      glibenclamide on the functional activity of mitochondrial kinases. Both diazoxide
      and glibenclamide did not change the in situ ADP sensitivity in the presence or
      absence of creatine (apparent K(m) values for ADP were, respectively, 59 +/- 9
      and 379 +/- 45 microm). Similarly, stimulation of the mitochondrial respiration
      with AMP in the presence of ATP due to adenylate kinase activity was not affected
      by the modulators of K(ATP) channels. However, when succinate was used as
      substrate, diazoxide significantly inhibited basal respiration by 22% and maximal
      respiration by 24%. Thus, at a cardioprotective dose, the main functional effect
      of diazoxide depends on respiratory substrates and seems not to be related to
      K(ATP) channel activity.

PMID- 10970895
TI  - The super anti-apoptotic factor Bcl-xFNK constructed by disturbing intramolecular
      polar interactions in rat Bcl-xL.
AB  - A powerful artificial anti-apoptotic factor will be useful for medical
      applications of the future therapies for many diseases by prolonging survival of
      sick cells. For constructing it, we designed the super anti-apoptotic factor by
      disturbing three intramolecular polar interactions among alpha-helix structures
      of Bcl-x(L). The resultant mutant Bcl-x(L), named Bcl-xFNK, was expected to make
      the pore-forming domain more mobile and flexible than the wild-type. When
      overexpressed in Jurkat cells, Bcl-xFNK was markedly more potent in prolonging
      survival following apoptosis-inducing treatment with a kind of cell death
      cytokines (anti-Fas), a protein kinase inhibitor (staurosporine), cell cycle
      inhibitors (TN-16, camptothecin, hydroxyurea, and trichostatin A), or oxidative
      stress (hydrogen peroxide and paraquat) than wild-type Bcl-x(L). Furthermore, the
      transfectants of bcl-xFNK became more resistant against a calcium ionophore and
      even a heat treatment than wild-type Bcl-x(L). In addition, Bcl-xFNK showed
      marked anti-apoptotic activity in Chinese hamster ovary and Jurkat cells deprived
      of serum. Thus, Bcl-xFNK may be the first mutant generated by site-directed
      mutagenesis of Bcl-x(L) with a gain-of-function phenotype. Interestingly, Bcl
      xFNK was found to allow interleukin-3-dependent FDC-P1 to grow without
      interleukin-3, but not BaF/3. In Bcl-xFNK transfectants of FDC-P1 and Jurkat, the
      p42/p44 mitogen-activated protein kinase was activated by 2 to 5 times, but not
      in those of BaF/3 and Chinese hamster ovary. Bcl-xFNK might gain a new function
      to activate the mitogen-activated protein kinase in a cell-type specific manner.
      The findings of this study suggest that the central alpha5-alpha6 pore-forming
      region of anti-apoptotic factor Bcl-x(L) has a pivotal role in suppressing
      apoptosis.

PMID- 10970896
TI  - Mutational analysis of the mitochondrial copper metallochaperone Cox17.
AB  - The copper metallochaperone Cox17 is proposed to shuttle Cu(I) ions to the
      mitochondrion for the assembly of cytochrome c oxidase. The Cu(I) ions are
      liganded by cysteinyl thiolates. Mutational analysis on the yeast Cox17 reveals
      three of the seven cysteinyl residues to be critical for Cox17 function, and
      these three residues are present in a Cys-Cys-Xaa-Cys sequence motif. Single
      substitution of any of these three cysteines with serines results in a
      nonfunctional cytochrome oxidase complex. Cells harboring such a mutation fail to
      grow on nonfermentable carbon sources and have no cytochrome c oxidase activity
      in isolated mitochondria. Wild-type Cox17 purified as untagged protein binds
      three Cu(I) ions/molecule. Mutant proteins lacking only one of these critical Cys
      residues retain the ability to bind three Cu(I) ions and are imported within the
      mitochondria. In contrast, Cox17 molecules with a double Cys --> Ser mutation
      exhibit no Cu(I) binding but are still localized to the mitochondria. Thus,
      mitochondrial uptake of Cox17 is not restricted to the Cu(I) conformer of Cox17.
      COX17 was originally cloned by virtue of complementation of a mutant containing a
      nonfunctional Cys --> Tyr substitution at codon 57. The mutant C57Y Cox17 fails
      to accumulate within the mitochondria but retains the ability to bind three Cu(I)
      ions. A C57S Cox17 variant is functional, and a quadruple Cox17 mutant with
      C16S/C36S/C47S/C57S substitutions binds three Cu(I) ions. Thus, only three
      cysteinyl residues are important for the ligation of three Cu(I) ions. A novel
      mode of Cu(I) binding is predicted.

PMID- 10970897
TI  - The core histone N termini function independently of linker histones during
      chromatin condensation.
AB  - The relationships between the core histone N termini and linker histones during
      chromatin assembly and salt-dependent chromatin condensation were investigated
      using defined chromatin model systems reconstituted from tandemly repeated 5 S
      rDNA, histone H5, and either native "intact" core histone octamers or "tailless"
      histone octamers lacking their N-terminal domains. Nuclease digestion and
      sedimentation studies indicate that H5 binding and the resulting constraint of
      entering and exiting nucleosomal DNA occur to the same extent in both tailless
      and intact chromatin arrays. However, despite possessing a normal chromatosomal
      structure, tailless chromatin arrays can neither condense into extensively folded
      structures nor cooperatively oligomerize in MgCl(2). Tailless nucleosomal arrays
      lacking linker histones also are unable to either fold extensively or
      oligomerize, demonstrating that the core histone N termini perform the same
      functions during salt-dependent condensation regardless of whether linker
      histones are components of the array. Our results further indicate that
      disruption of core histone N termini function in vitro allows a linker histone
      containing chromatin fiber to exist in a decondensed state under conditions that
      normally would promote extensive fiber condensation. These findings have key
      implications for both the mechanism of chromatin condensation, and the regulation
      of genomic function by chromatin.

PMID- 10970898
TI  - Maurotoxin versus Pi1/HsTx1 scorpion toxins. Toward new insights in the
      understanding of their distinct disulfide bridge patterns.
AB  - Maurotoxin (MTX) is a scorpion toxin acting on several K(+) channel subtypes. It
      is a 34-residue peptide cross-linked by four disulfide bridges that are in an
      "uncommon" arrangement of the type C1-C5, C2-C6, C3-C4, and C7-C8 (versus C1-C5,
      C2-C6, C3-C7, and C4-C8 for Pi1 or HsTx1, two MTX-related scorpion toxins). We
      report here that a single mutation in MTX, in either position 15 or 33, resulted
      in a shift from the MTX toward the Pi1/HsTx1 disulfide bridge pattern. This shift
      is accompanied by structural and pharmacological changes of the peptide without
      altering the general alpha/beta scaffold of scorpion toxins.

PMID- 10970899
TI  - Inhibition of TRP3 channels by lanthanides. Block from the cytosolic side of the
      plasma membrane.
AB  - The lanthanide ions La(3+) and Gd(3+) block Ca(2+)-permeable cation channels and
      have been used as important tools to characterize channels of the transient
      receptor potential (TRP) family. However, widely different concentrations of
      La(3+) and Gd(3+) have reportedly been required for block of TRP3 channels in
      various expression systems. The present study provides a possible explanation for
      this discrepancy. After overexpression of TRP3 in Chinese hamster ovary cells,
      whole-cell currents through TRP3 were reversibly inhibited by La(3+) with an
      EC(50) of 4 microm. For comparison, the organic blocker SKF96365 required an
      EC(50) of 8 microm. Gd(3+) blocked with an EC(50) of 0.1 microm, but this block
      was slow in onset and was not reversible after wash-out. When the two lanthanides
      were added to the cytosolic side of inside-out patches, block was achieved with
      considerably lower concentrations (EC(50) for La(3+), 0.02 microm; EC(50) for
      Gd(3+), 0.02 microm). Uptake of La(3+) into the cytosol of Chinese hamster ovary
      cells was demonstrated with intracellular fura-2. We conclude that lanthanides
      block TRP3 more potently from the cytosolic than from the extracellular side of
      the plasma membrane and that uptake of lanthanides will largely affect the
      apparent EC(50) values after extracellular application.

PMID- 10970900
TI  - Second stalk of ATP synthase. Cross-linking of gamma subunit in F1 to truncated
      Fob subunit prevents ATP hydrolysis.
AB  - ATP synthase consists of two portions, F(1) and F(o), connected by two stalks: a
      central rotor stalk containing gamma and epsilon subunits and a peripheral,
      second stalk formed by delta and two copies of F(o)b subunits. The second stalk
      is expected to keep the stator subunits from spinning along with the rotor. We
      isolated a TF(1)-b'(2) complex (alpha(3)beta(3)gammadeltaepsilonb'(2)) of a
      thermophilic Bacillus PS3, in which b' was a truncated cytoplasmic fragment of
      F(o)b subunit, and introduced a cysteine at its N terminus (bc'). Association of
      b'(2) or bc'(2) with TF(1) did not have significant effect on ATPase activity. A
      disulfide bond between the introduced cysteine of bc' and cysteine 109 of gamma
      subunit was readily formed, and this cross-link caused inactivation of ATPase.
      This implies that F(o)b subunit bound to stator subunits of F(1) with enough
      strength to resist rotation of gamma subunit and to prevent catalysis. Contrary
      to this apparent tight binding, some detergents such as lauryldodecylamine oxide
      tend to cause release of b'(2) from TF(1).

PMID- 10970901
TI  - Apoptosis induced by cadmium in human lymphoma U937 cells through Ca2+-calpain
      and caspase-mitochondria- dependent pathways.
AB  - Apoptosis induced by cadmium has been shown in many tissues in vivo and in
      cultured cells in vitro. However, its molecular mechanism is not fully
      understood. When the human histiocytic lymphoma cell line U937 was treated with
      cadmium for 12 h, evidence of apoptotic features, including change in nuclear
      morphology, DNA fragmentation, formation of DNA ladder in agarose gel
      electrophoresis, and phosphatidylserine externalization, were obtained. Moreover,
      loss of the mitochondrial membrane potential (Deltapsi(m)) was observed in the
      cadmium-treated cells and was inhibited by a broad caspase inhibitor (Z-VAD-FMK).
      Caspase inhibitors suppressed the DNA fragmentation in the order of Z-VAD-FMK >
      caspase-8 inhibitor > caspase-3 inhibitor. Expression of Bcl-x(L) and Bid
      decreased significantly in the cadmium-treated cells, although no apparent change
      in Bcl-2 and Bax expression was found. Tetrakis-(2-pyridylmethyl) ethylendiamine,
      a cell-permeable heavy metal chelator, partially reversed the increase of
      fluorescence of Fura-2 in the cadmium-treated cells. In addition, verapamil (70
      microm), a voltage-dependent Ca(2+) channel blocker, inhibited the DNA
      fragmentation induced by cadmium less than 100 microm and decreased the
      fluorescence of Fura-2. Cadmium up-regulated the expression of type 1 inositol
      1,4,5-trisphosphate receptor (IP(3)R) but not type 2 or type 3 IP(3)R. Calpain
      inhibitors I and II partially prevented DNA fragmentation. No effects of Z-VAD
      FMK on the expression of type 1 IP(3)R or of calpain inhibitors on the loss of
      Deltapsi(m) were observed. These results suggest that cadmium possibly induced
      apoptosis in U937 cells through two independent pathways, the Ca(2+)-calpain
      dependent pathway and the caspase-mitochondria-dependent pathway.

PMID- 10970902
TI  - NF-kappa B regulates transcription of the mouse telomerase catalytic subunit.
AB  - Expression of the telomerase catalytic subunit (TERT) is the rate-limiting
      determinant of telomerase activity in most cells. Analysis of the mouse TERT
      promoter revealed a potential NF-kappaB binding site 350 base pairs upstream from
      the translational start site. An oligonucleotide from this region of the TERT
      promoter bound to proteins in a nuclear extract prepared from a mouse hepatoma
      cell line. These proteins were identified as NF-kappaB by a number of criteria:
      1) the protein complex formed on the TERT oligonucleotide had an electrophoretic
      mobility similar to that formed on an NF-kappaB consensus oligonucleotide; 2)
      protein binding to this site was enhanced by NF-kappaB activators tumor necrosis
      factor-alpha, phorbol 12-myristate 13-acetate, and interleukin-1beta; and 3) the
      complex was specific and could be supershifted with antibodies against the p50 or
      p65 NF-kappaB subunits. The NF-kappaB binding site from the mouse TERT promoter
      activated transcription when fused to a basal SV40 promoter and enhanced the
      activity of the native TERT promoter in mouse hepatoma cells stimulated with
      phorbol 12-myristate 13-acetate. Transcriptional activation by the TERT NF-kappaB
      site could also be enhanced by co-transfection with an NF-kappaB1 expression
      vector. NF-kappaB may therefore contribute to the activation of TERT expression
      observed in mouse tissue.

PMID- 10970904
TI  - Novel protein-disulfide isomerases from the early-diverging protist giardia
      lamblia

PMID- 10970903
TI  - Assembly of SNARE core complexes prior to neurotransmitter release sets the
      readily releasable pool of synaptic vesicles.
AB  - Precise regulation of neurotransmitter release is essential for the normal
      function of neural networks, but the mechanisms involved are largely unclear.
      Using superfused synaptosomes, we have studied the readily releasable pool of
      synaptic vesicles, measured as the amount of release triggered by hypertonic
      sucrose. We show that activation of presynaptic metabotropic glutamate receptors
      by dihydroxyphenylglycine and stimulation of protein kinase C by phorbol esters
      enhance the readily releasable pool of glutamate. Although the molecular nature
      of the readily releasable pool is unknown, one possibility is that during its
      generation, SNARE proteins form full core complexes, and that core complex
      formation occurs prior to neurotransmitter release. To test this possibility, we
      employed N-ethylmaleimide (NEM), an inhibitor of the ATPase N-ethylmaleimide
      sensitive factor that dissociates core complexes, to study the relation of the
      readily releasable pool to core complex assembly in synaptosomes. NEM induced a
      dose-dependent increase in the readily releasable pool of neurotransmitters but
      by itself did not trigger release. Direct measurements of core complexes
      confirmed that NEM caused an increase in the levels of SNARE core complexes under
      these conditions. Our data suggest that in the readily releasable pool of
      synaptic vesicles, SNARE proteins are fully assembled into core complexes, and
      that SNARE complex assembly is a target of presynaptic regulation.

PMID- 10970905
TI  - p21Waf1/Cip1 is an assembly factor required for platelet-derived growth factor
      induced vascular smooth muscle cell proliferation

PMID- 10970906
TI  - Better treatment for dual diagnosis patients.

PMID- 10970907
TI  - This Month's highlights

PMID- 10970908
TI  - Emergency psychiatry: critical incident stress management: I. Interventions and
      effectiveness.

PMID- 10970909
TI  - State health care reform: the effects of program realignment on severely mentally
      ill persons in California's community-based mental health system.

PMID- 10970910
TI  - Datapoints: salary changes among independent psychologists by gender and
      experience.

PMID- 10970912
TI  - Web sites worth watching

PMID- 10970911
TI  - Rehab rounds: outcomes of patients with schizophrenia in a family-style,
      residential, community-based program in Italy.

PMID- 10970913
TI  - Assessment and classification of patients with psychiatric and substance abuse
      syndromes. 1989.

PMID- 10970914
TI  - Dual diagnosis: 15 years of progress.

PMID- 10970915
TI  - A review of herbal medicines for psychiatric disorders.
AB  - OBJECTIVE: This review examines herbs commonly used for psychiatric symptoms-St.
      John's wort, kava, ginkgo biloba, and valerian. METHODS: MEDLINE was searched for
      articles related to the use of herbs in psychiatry published after 1990. A
      secondary search examined sources cited in articles obtained from the MEDLINE
      search. RESULTS: Of nine controlled and standardized trials of St. John's wort,
      five showed the herb's superiority to placebo, and four found no differences in
      effectiveness when compared with antidepressant drugs. The pharmacologically
      active components are not known. Several double-blind, placebo-controlled trials
      have demonstrated the anxiolytic efficacy of kava, but these studies had ill
      defined patient populations, small sample sizes, and short treatment duration.
      All but one of 40 controlled trials of ginkgo extracts in the treatment of
      dementia found clinically significant improvement in memory loss, concentration,
      fatigue, anxiety, and depressed mood. Most studies of gingko had poorly defined
      patient populations and small sample sizes and used nonstandard measures. A
      recent well-designed multicenter study showed significantly less decline in
      cognitive function among patients with dementia receiving gingko. Valerian has
      been shown to decrease sleep latency and nocturnal awakenings and improve
      subjective sleep quality, but placebo effects were marked in some studies, and in
      some cases the beneficial effects were not seen until two to four weeks of
      therapy. CONCLUSIONS: Although evidence of the efficacy of herbal preparations in
      treating psychiatric conditions is growing, translating the results of efficacy
      studies into effective treatments for patients is hampered by the chemical
      complexity of the products, the lack of standardization of commonly available
      preparations, and the paucity of well-controlled studies.

PMID- 10970916
TI  - Quality of life of homeless persons with mental illness: results from the course
      of-homelessness study.
AB  - OBJECTIVE: The quality of life of homeless persons with mental illness was
      compared with that of homeless persons without mental illness. METHODS:
      Subjective and objective quality-of-life ratings were obtained in face-to-face
      interviews with 1,533 homeless adults in Los Angeles, who were identified using
      probability sampling of people on the streets and at shelters and meal
      facilities; 520 subjects were tracked for 15 months. Ratings of homeless persons
      with and without mental illness were compared using chi square tests and
      regression analyses. RESULTS: Mentally ill homeless persons were significantly
      more likely than those without mental illness to receive Supplemental Security
      Income, Social Security Disability Insurance, Veterans Affairs disability
      benefits, or Medicaid. However, those with mental illness still fared
      significantly worse in terms of physical health, level of subsistence needs met,
      victimization, and subjective quality of life. Differences between groups in the
      subjective quality-of-life ratings were accounted for by modifiable factors such
      as income and symptoms rather than by nonmodifiable demographic characteristics.
      CONCLUSIONS: Interventions most likely to improve the quality of life of homeless
      persons with mental illness include those that stress maintenance of stable
      housing and provision of food and clothing and that address physical health
      problems and train individuals to minimize their risk of victimization.
      Interventions that decrease depressive symptoms might also improve subjective
      quality of life.

PMID- 10970917
TI  - The case management relationship and outcomes of homeless persons with serious
      mental illness.
AB  - OBJECTIVE: The effect of the case management relationship on clinical outcomes
      was examined among homeless persons with serious mental illness. METHODS: The
      sample consisted of the first two cohorts that entered the Access to Community
      Care and Effective Services and Supports (ACCESS) program, a five-year
      demonstration program for mentally ill homeless persons funded by the Center for
      Mental Health Services in 1994. At baseline, three months, and 12 months, clients
      were characterized as not having a relationship with their case manager or as
      having a low or high therapeutic alliance with their case manager. Analyses were
      conducted to test the association between the case manager relationship at
      baseline, three months, and 12 months and clinical outcomes at 12 months.
      RESULTS: Multivariate analyses of covariance were conducted for 2,798 clients who
      had outcome data at 12 months. No significant associations were found between the
      relationship with the case manager at baseline and outcomes at 12 months. At
      three months, clients who had formed an alliance with their case manager had
      significantly fewer days of homelessness at 12 months. Clients who reported a
      high alliance with their case manager at 12 months had significantly fewer days
      of homelessness at 12 months than those with a low alliance, and those with a low
      alliance at 12 months had fewer days of homelessness than clients who reported no
      relationship with their case manager. Clients with a higher alliance at both
      three and 12 months reported greater general life satisfaction at 12 months.
      CONCLUSIONS: The study found that clients' relationship with their case manager
      was significantly associated with homelessness and modestly associated with
      general life satisfaction.

PMID- 10970918
TI  - Measuring clients' satisfaction with self-help agencies.
AB  - OBJECTIVE: Clients' satisfaction with their involvement in treatment decisions
      has been largely overlooked in the formulation of satisfaction measures. The
      authors describe the development of a scale that assesses clients' satisfaction
      with services and with their involvement in treatment decisions. METHODS: Long
      term users of four client-operated mental health self-help agencies were
      interviewed at baseline (N=310) and six months (N=248) using the 11-item Self
      Help Agency Satisfaction Scale (SHASS). The scale was developed on the basis of
      consumers' input about their satisfaction with services and their involvement in
      treatment decisions. To explore the relationship between satisfaction as measured
      by the SHASS and outcomes, the six-month interview included four outcome measures
      independent and assisted social functioning, symptom severity, and a sense of
      personal empowerment. Internal consistency, stability, and discriminant validity
      were evaluated. RESULTS: Factor analyses confirmed that the SHASS has two
      subscales, one assessing service satisfaction and the other assessing
      satisfaction with involvement in treatment decisions. The scale and its subscales
      showed high internal consistency, moderate stability, and discriminant validity.
      The SHASS subscales showed modest associations with two of four outcome measures
      assisted and independent social functioning. CONCLUSIONS: The SHASS is a brief
      instrument that can be used to measure clients' satisfaction with their
      involvement in treatment in mental health self-help agencies.

PMID- 10970919
TI  - Evaluation of a mobile crisis program: effectiveness, efficiency, and consumer
      satisfaction.
AB  - OBJECTIVE: The effectiveness and efficiency of a mobile crisis program in
      handling 911 calls identified as psychiatric emergencies were evaluated, and the
      satisfaction of consumers and police officers with the program was rated.
      METHODS: The study retrospectively examined differences in subjects' demographic
      characteristics, hospitalization and arrest rates, and costs for 73 psychiatric
      emergency situations handled by a mobile crisis team and 58 psychiatric emergency
      situations handled by regular police intervention during three months in 1995.
      Consumers' and police officers' satisfaction with the mobile crisis program was
      evaluated through Likert-type scales. RESULTS: Fifty-five percent of the
      emergencies handled by the mobile crisis team were managed without psychiatric
      hospitalization of the person in crisis, compared with 28 percent of the
      emergencies handled by regular police intervention, a statistically significant
      difference. The difference in arrest rates for persons handled by the two groups
      was not statistically significant. The average cost per case was 23 percent less
      for persons served by the mobile crisis team. Both consumers and police officers
      gave positive ratings to the mobile crisis program. CONCLUSIONS: Mobile crisis
      programs can decrease hospitalization rates for persons in crisis and can provide
      cost-effective psychiatric emergency services that are favorably perceived by
      consumers and police officers.

PMID- 10970920
TI  - Race, age, and back pain as factors in completion of residential substance abuse
      treatment by veterans.
AB  - OBJECTIVE: Variables associated with successful completion of residential
      substance abuse treatment were identified. METHODS: The records of 340 veterans
      admitted to a 120-day substance abuse treatment program were retrospectively
      analyzed. The likelihood of successful treatment completion was calculated as a
      function of race, age, gender, psychiatric diagnosis, past suicide attempts,
      homelessness, legal history, childhood physical or sexual abuse, parental history
      of addiction, multiple substance dependence, medical problems, and the race of
      the therapist. Univariate analysis and logistic regression analysis were used to
      identify variables that were significant predictors of treatment completion.
      RESULTS: Overall, 66 percent of veterans completed the program. Eighty-two
      percent of the veterans admitted to the program were black, and 16 percent were
      white. The completion rate of black veterans (71 percent) was significantly
      higher than that of white veterans (49 percent). Veterans completing treatment
      were significantly more likely to be older, by an average of two years, than
      those who did not complete treatment. The association between younger age and
      failure to complete the program was largely accounted for by younger black
      veterans. Veterans with back pain were significantly less likely to complete
      treatment than those without back pain. Completion rates did not vary by the
      other variables examined. In the regression analysis that included age, race, and
      back pain, each variable, when adjusted by the other variables, was a significant
      predictor of completion. CONCLUSIONS: White patients were less likely to complete
      residential substance abuse treatment in a program in which the majority of both
      therapists and patients were black. Younger black veterans and those with back
      pain were also less likely to complete treatment.

PMID- 10970921
TI  - Planning by older mothers for the future care of offspring with serious mental
      illness.
AB  - OBJECTIVE: This study examined permanency planning by older mothers for their
      adult offspring with long-term mental illness, including extent of residential
      and financial planning, desire for future family care, and perceived need for and
      use of services to assist with planning. METHODS: Mail surveys were completed by
      157 mothers (mean age, 67 years) from 41 states who lived with and provided care
      to adult offspring with serious mental disorders (mean age, 38 years). The
      offspring were mostly males (76 percent) and had diagnoses primarily of
      schizophrenia or schizoaffective disorder (60 percent), multiple diagnoses (20
      percent), or bipolar disorder (16 percent). RESULTS: Only 11 percent of mothers
      reported definite plans for their offspring's future residence, and many had done
      little or no planning. Three-quarters of respondents hoped that another family
      member would assume care, yet only one-quarter thought such arrangements would
      definitely occur. Two-thirds of the respondents had completed financial plans.
      Although more than two-thirds expressed the need for services to help with
      planning, less than one-third had used such services. More than half reported
      awareness of age-related changes in themselves or their spouse as the primary
      reason for planning. CONCLUSIONS: Older parents of adults with long-term mental
      illness need professional help with planning for their offspring's future. This
      assistance should focus on mechanisms such as estate planning to enable case
      management and other services after parents' death. The involvement of
      nondisabled siblings in planning should also be encouraged.

PMID- 10970922
TI  - The relationship between patients' gender and violence leading to staff injuries.
AB  - OBJECTIVE: Although recent research has found similar rates of violence by female
      and male patients who have serious mental disorders, it is less clear whether
      violence by female patients is as likely to result in injury as violence by male
      patients. This study examined the relationship between violent patients' gender
      and injury to staff members on an inpatient unit. METHODS: All injuries to staff
      caused by violent behavior by patients on a locked university-based short-term
      inpatient unit were identified in a search of institutional records from October
      1988 to June 1999. We reviewed the medical charts of the 76 patients who injured
      staff members to compare their demographic and clinical characteristics with
      those of 314 patients hospitalized during the same period who did not injure
      staff. RESULTS: Nearly half of the injuries (45 percent) were caused by female
      patients. Moreover, the proportion of injuries caused by female and male patients
      was similar to the proportion of females and males in the comparison group.
      Multivariate logistic regression analysis showed that patients' gender was not
      associated with injury to staff, even when the analyses controlled for other
      correlates of violence such as history of violence, violent thought content
      expressed in the admission mental status examination, and history of
      noncompliance with medication. CONCLUSIONS: The findings suggest that injuries to
      staff members on a unit treating both men and women are as likely to be caused by
      violence by female patients as by male patients. When a female patient exhibits
      signs of an elevated risk of violence, the significance of that risk should not
      be discounted on the basis of her gender.

PMID- 10970923
TI  - Cost-utility analysis in depression: the McSad utility measure for depression
      health states.
AB  - Cost-utility analysis, used increasingly over the past decade to analyze costs
      and effects in treating physical diseases, has received little attention in
      psychiatry. This article briefly introduces the concepts and methods of utility
      measurement and illustrates it using depression as an example. The authors
      describe the McSad health state classification system for depression, a direct
      utility measure for depression, and report results of an application of McSad
      among 105 patients who had a recent history of depression. Utility measures
      express patient preferences for specific health states on a scale ranging from 0,
      representing death, to 1, representing perfect health. These scores provide the
      weights used to calculate the number of quality-adjusted life-years gained by an
      intervention or service. McSad allows a patient's depression health state to be
      classified according to level of functioning in six dimensions of depression and
      to be compared with other hypothetical depression health states in order to
      produce utility scores indicating the patient's relative preferences.

PMID- 10970924
TI  - Group therapy program for African-American veterans with posttraumatic stress
      disorder.
AB  - A Vet Center's group therapy treatment program for African-American veterans with
      posttraumatic stress disorder (PTSD) has met regularly and expanded since it was
      established in 1984. Program attributes described by participants as particularly
      helpful include facilitating open communication of thoughts and feelings among
      African-American men; providing support for coping with the intrapsychic, social,
      and economic effects of racism; increasing knowledge about the causes,
      consequences, and treatment of PTSD; and decreasing emotional and social
      isolation. The program appears to be a useful treatment for African-American
      veterans with PTSD.

PMID- 10970926
TI  - Obtaining informed consent of patients at risk of neuroleptic malignant syndrome.
AB  - Thirty psychiatrists completed a mailed questionnaire about their attitudes
      toward obtaining informed consent and about the frequency with which they
      obtained it from patients taking neuroleptic medications who were at risk of
      tardive dyskinesia, a relatively common but nonfatal side effect, and neuroleptic
      malignant syndrome (NMS), an uncommon but potentially fatal side effect. Only one
      psychiatrist reported always or almost always informing patients about the risk
      of NMS. Psychiatrists were significantly less likely to inform patients about the
      risk of NMS than the risk of tardive dyskinesia. Psychiatrists may not be aware
      of the risk of NMS and may not know what information to provide to patients.

PMID- 10970925
TI  - Computerized monitoring of valproate and physician responsiveness to laboratory
      studies as a quality indicator.
AB  - Using computerized pharmacy, laboratory, and hospitalization data from a large
      state psychiatric hospital system, this study examined physician responses to
      laboratory studies obtained in the course of therapeutic drug monitoring.
      Computerized monitoring modules based on physician-developed guidelines
      identified out-of-range laboratory values and searched for appropriate
      corresponding physician responses within clinically driven, mathematically
      adjusted time frames. Valproate monitoring in four metropolitan hospitals showed
      that appropriate physician responses were associated with shorter hospital stays
      for patients and were predictive of length of stay in a multiple regression
      analysis (p<.001). After physicians received didactic feedback, the percentage of
      appropriate responses to low serum valproate levels increased.

PMID- 10970928
TI  - Psychiatric aspects of violence: issues in prevention and treatment working with
      AIDS bereavement: A comprehensive approach for mental health providers

PMID- 10970927
TI  - Effects of divalproex versus lithium on length of hospital stay among patients
      with bipolar disorder.
AB  - The medical records of all inpatients with bipolar disorder at the Connecticut
      Mental Health Center in 1997 were examined to compare length of stay for patients
      who began monotherapy with divalproex (27 treatment starts) and lithium (20
      treatment starts). No statistically significant difference was found in length of
      stay (11. 5+/-6.9 and 10.3+/-5.2 days for patients on divalproex and lithium,
      respectively) or other length-of-stay variables. Demographic variables,
      diagnostic variables, and dosages of neuroleptics and benzodiazepines used
      adjunctively were similar as well. Dosages and blood levels for divalproex and
      lithium were consistent with practice guidelines. Prospective randomized studies
      are needed to compare the cost-effectiveness of divalproex and of lithium in the
      treatment of bipolar disorder.

PMID- 10970929
TI  - Defense and Veterans Head Injury Program: background and overview.
AB  - Traumatic brain injury (TBI) is the principal cause of death and disability for
      young Americans, with an estimated societal cost of over $39 billion per year.
      The Defense and Veterans Head Injury Program (DVHIP) represents a close
      collaboration among the Departments of Defense (DoD) and Veterans Affairs (DVA),
      the Brain Injury Association (BIA), and the International Brain Injury
      Association (IBIA). Its principal mission is to ensure that military and veteran
      patients with head injury receive TBI-specific evaluation, treatment,
      rehabilitation, and follow-up, while at the same time addressing the readiness
      mission of the military and helping to define optimal care for victims of TBI
      nationwide. Defense and Veterans Head Injury Program activities can be grouped
      into three broad classes: (1) TBI education, community service, and primary
      prevention projects; (2) combined TBI clinical treatment, rehabilitation, and
      clinical research projects; and (3) clinically linked TBI laboratory research
      projects. It is thus based on a prudent integration of clinical care and follow
      up with programmatic clinical and clinically related laboratory research, TBI
      prevention, and education. This previously nonexistent clinical infrastructure
      now offers a valuable base for ongoing TBI clinical research.

PMID- 10970930
TI  - A home program of rehabilitation for moderately severe traumatic brain injury
      patients. The DVHIP Study Group.
AB  - We have recently reported the results of a prospective controlled randomized
      trial comparing home versus inpatient cognitive rehabilitation for patients with
      moderate to severe head injury. That study showed no overall difference in
      outcomes between the two groups.(1) In this article, we provide further details
      of the home program arm of the study. All patients in the home program received
      medical treatment as needed, a multidisciplinary in-hospital evaluation, and TBI
      counseling before entering the eight-week home program, which then included
      guidance on home activities, as well as weekly telephone calls from a psychiatric
      nurse.

PMID- 10970931
TI  - Factors predicting return to work following mild traumatic brain injury: a
      discriminant analysis.
AB  - Studies of mild traumatic brain injury (MTBI) suggest that most individuals
      recover rapidly and return to their everyday activities. However, a percentage of
      MTBI patients report persistent problems with cognitive, physical, and emotional
      symptoms. There is also evidence that some experience changes in occupational
      functioning following MTBI. The current study used a stepwise discriminant
      function analysis (DFA) to examine the role of injury severity variables,
      cognitive performance, and ratings of symptoms of TBI in predicting work status
      following MTBI. Subjects included 121 MTBI patients who were all active-duty
      military personnel. The stepwise DFA revealed that age and three cognitive
      variables (verbal memory, verbal fluency, and a speed test of planning and
      strategy) were predictive of work status 3-15 months following a documented MTBI,
      correctly classifying work status 68.8% of the time. A cross-validation DFA was
      conducted, with a 66.1% correct classification rate. These findings highlight the
      importance of cognitive impairments in identifying those at risk for occupational
      impairment following MTBI.

PMID- 10970932
TI  - Acute impact of severe traumatic brain injury on family structure and coping
      responses.
AB  - Family stress following traumatic brain injury (TBI) is well documented. Previous
      studies have shown that family adaptation and the use of coping strategies
      moderate the stresses of TBI in the long term. However, relatively little is
      known about the impact on the family and family response during the acute stage
      of recovery. The present study used Olson's Circumplex Model to examine acute
      changes in family structure and examined changes in coping responses pre- and
      post-TBI. Wives of 20 male TBI survivors completed the Couples Version of the
      Family Adaptability and Cohesion Evaluation Scales-II (FACES-II) and the Coping
      Responses Inventory (CRI). These questionnaires were completed retrospectively
      for a stressful event that occurred six months prior to the TBI, then for the
      current period following the TBI. Results found that 60% of all families
      experienced a significant change in structure following TBI. As predicted by the
      Circumplex Model, balanced families changed most, with 70% changing to the
      extreme type post-TBI. Focus of coping (problem versus emotion) and coping
      techniques (cognitive versus behavioral) also changed significantly from pre- to
      post-TBI and differed, depending on post-TBI family structure. Family
      interventions based on these differences in family structure and coping are
      presented.

PMID- 10970933
TI  - A longitudinal investigation of the concordance between individuals with
      traumatic brain injury and family or friend ratings on the Katz adjustment scale.
AB  - Changes in the level of agreement (concordance) between self and family or friend
      reporting on the Katz Adjustment Scale (KAS) from 6 to 12 months postinjury were
      assessed in 55 individuals with traumatic brain injury (IwTBI). Although the
      concordance between self and family/friend reports significantly increased over
      the course of recovery, possibly reflecting improvements in awareness, the
      concordance showed limited relationship to measures of injury severity and
      neuropsychological functioning. Concordance did not significantly relate to
      clinicians' ratings of inaccurate insight and self-appraisal on the awareness
      item from the Neurobehavioral Rating Scale (NBRS). Clinicians' ratings of
      awareness demonstrated only limited relationship to measures of injury severity
      and neuropsychological functioning, as well. Although similar results in the
      literature have been interpreted as demonstrating that awareness, defined as
      concordance, is possibly a unique construct separate from injury severity and
      neuropsychological functioning, an alternative hypothesis is presented concerning
      other, noninjury factors that may affect the level of agreement in problem
      reporting between IwTBI and family/friend informants.

PMID- 10970934
TI  - Reliability and validity of the Wisconsin HSS Quality Of Life inventory in
      traumatic brain injury.
AB  - The present investigation examined the psychometric properties of the Wisconsin
      HSS Quality of Life Inventory (WI HSS QOL) when used in the study of traumatic
      brain injury (TBI). The WI HSS QOL is a theoretically based measure that assesses
      QOL via level of need satisfaction as conceptualized in Maslow's theory of human
      needs. Both internal consistency and test-retest reliability were demonstrated in
      a group of individuals with moderate to severe TBI. The demonstrated consistency
      of the participants' self-reports indicates that QOL can be reliably assessed
      from the survivor's perspective. Cluster analytic results generally supported the
      construct validity of the measure's use in TBI. The cluster solution reflected
      four of the five theoretical need categories; however, the fifth category, "self
      actualization" needs, did not emerge as a single cluster as expected. This
      deviation from the theoretical model may relate to participants' difficulties in
      understanding the relatively abstract items designed to assess the concept of
      self-actualization. Overall, the WI HSS QOL holds significant promise as a
      measure of QOL in TBI.

PMID- 10970935
TI  - Opportunities for neuroprotection in traumatic brain injury.
AB  - Traumatic injury of the brain in man is normally followed by little or no
      recovery of function by the lesioned tissue. Neuroprotective strategies employed
      in the acute period after traumatic CNS injury attempt to use pharmacological
      tools to reduce the progressive secondary injury processes that follow after the
      initial lesion occurs to limit overall tissue damage. Results from experimental
      animal studies using a variety of drugs that modulate neurotransmitter function,
      scavenge free radicals, or interfere with cell death cascades point toward many
      new opportunities for pharmacological intervention in the acute and subacute
      period after traumatic brain injury.

PMID- 10970936
TI  - Brief neurocognitive batteries: a review and preview.

PMID- 10970938
TI  - Revisiting autonomy and informed consent.

PMID- 10970937
TI  - Possible applications for dopaminergic agents following traumatic brain injury:
      part 1.

PMID- 10970939
TI  - Reducing the extent of injury using telematics.

PMID- 10970940
TI  - [Evaluation of corticosteroid replacement therapy and its effect on bones in
      Addison's disease].
AB  - Assessment of patients on steroid replacement therapy is important to avoid the
      consequences of overtreatment such as osteoporosis. The aim of this prospective
      study is to evaluate the severity and the etiology of osteopenia in 24 patients
      (15 women, 9 men) with Addison's disease receiving 30 mg hydrocortisone. Mean age
      of patients was 55 15 years. Osteoporosis, diagnosed by the measurement of bone
      mineral density (BMD) at the level of lumbar spine and right hip, was found in
      58% of patients, i.e. in 10 women and 4 men. The latter had normal testosterone
      levels while seven women had an early menopause, the etiology of their Addison's
      disease being autoimmune. Three were on hormonotherapy. Correlations were found
      between BMD in the femoral neck and hip and the dose of hydrocortisone
      (mg/m(2)/day; mg/kg/day), the duration of treatment and 24 hr-cortisoluria/g
      creatinine. Multivariate analysis shows that 24-hr cortisoluria/g creatinine is a
      good predictor of BMD values. Thus, osteoporosis is frequent in Addison's disease
      and cortisoluria could be a useful tool to predict this complication.

PMID- 10970941
TI  - Hypothyroidism after iodine-131 or surgical therapy for Graves' disease
      hyperthyroidism.
AB  - BACKGROUND: The aim of this work was to describe late permanent hypothyroidism
      after iodine-131 or surgery, and to seek predictive factors of hypothyroidism for
      the two treatments. MATERIAL: From 1979 to 1994, 462 patients with Graves'
      disease hyperthyroidism underwent definitive treatment. Three hundred and fifty
      five patients were treated with low calculated doses of iodine-131, and 107
      patients with subtotal thyroidectomy. Life-table analysis was performed and the
      cumulative incidence of hypothyroidism was calculated by Kaplan-Meier's method,
      and survival (euthyroidism) within the groups was compared by the Mantel-Cox
      method. RESULTS: Of the 355 patients treated with one dose of 6.6 1.9 mCi of
      iodine-131, 246 became euthyroid after one dose, and 109 needed 2 or more doses.
      Twenty-two patients received one or more doses higher than 10 mCi. The
      probability of euthyroidism at 145 months after low-dose was 10. 19% and age,
      sex, pretreatment with antithyroid drugs, previous subtotal surgery did not
      influence the final outcome. Of the 107 surgically treated patients the
      probability of euthyroidism at 144 months was 56.1%. Age, sex, duration of
      hyperthyroidism, duration of antithyroid treatment, weight of thyroid resected,
      did not influence the final outcome. The weight of the thyroid remnant was 5.4
      1.5 g and the multivariate statistical model by conditional logistic regression
      showed that the weight of thyroid remnant was the only variable that influenced
      long-term thyroid function. CONCLUSIONS: There is no ideal dose of iodine-131
      that would correct hyperthyroidism in Graves disease without risk of
      hypothyroidism. Surgery is an alternative definitive treatment with a risk of
      hypothyroidism within the 2 first years, and a cumulative risk of hypothyroidism
      lower than with iodine-131.

PMID- 10970942
TI  - [Failure of bone marrow autograft in metastatic malignant adrenalcortical
      carcinoma].
AB  - BACKGROUND: Despite different therapeutic modalities (surgery, hormones therapy,
      chemotherapy), 5-year survival in patients with malignant adrenocortical
      carcinoma remains only 10% to 20%. Bone marrow grafts may be proposed to
      intensify treatment. CASE REPORT: In a 29-year-old patient with adrenocortical
      carcinoma with metastases to the lung and bone, an adjuvant bone marrow graft
      using peripheral stem cells was unsuccessful. Recurrence was observed at 3 months
      and overall survival was 2 years. DISCUSSION: Our case illustrates the
      feasibility of this approach but also emphasizes the relatively poor results
      obtains with only 2 years survival (1 year after the bone marrow graft),
      comparable with other classical modalities reported in the literature.

PMID- 10970943
TI  - Resistance to thyroid hormone in a family with no TRbeta gene anomaly: pathogenic
      hypotheses.
AB  - Syndromes of resistance to thyroid hormone (RTH) are almost always linked to a
      defective triiodothyronine-receptor B gene (TRB). Only six families with RTH
      exhibiting a normal TRB gene have been reported so far. We report another and
      discuss possible mechanisms. PATIENTS AND METHODS: We studied a kindred
      expressing a typical RTH phenotype. DNA was amplified and the TRB gene was
      sequenced. Linkage analysis assessed linkage between the TRB gene and RTH
      phenotype. RESULTS: Direct sequencing of the TRB gene failed to identify any
      anomaly in the coding exons. Linkage analysis demonstrated that the RTH phenotype
      was not linked to the TRB gene in this family. CONCLUSION: TRB1 and TRB2 genes
      were not defective in this family. Multiple mechanisms might account for this
      situation at the pre-receptor, receptor and post-receptor levels. The most likely
      hypothesis is the involvement of an abnormal nuclear cofactor serving a specific
      function in the regulation of thyroid hormone action.

PMID- 10970945
TI  - [Pituitary development and pathology of transcription factors].
AB  - Over the last 10 years, important data on pituitary development have been
      reported using spontaneous or experimental models of gene inactivation. The
      development pathways of the anterior pituitary lobe include organogenesis
      resulting in Rathke pouch formation and cell differentiation. Pituitary
      development is controlled by sequential series of specific signaling molecules
      and specific transcription factors. In humans, inactivation of Pit-1, Prop-1, Rpx
      and Ptx2 genes is responsible for pituitary combined deficiency. In this paper,
      updated data on the embryology of the pituitary gland and the clinical phenotypes
      of inactivation of pituitary transcription factors are reported.

PMID- 10970944
TI  - [Hypophyse 2000. Proceedings of a meeting. Tours, France, 7 April 2000].

PMID- 10970946
TI  - [Growth hormone insufficiency: diagnosis, treatment, results].
AB  - Growth hormone (GH) deficiency is not an unusual cause of short stature which, in
      absence of treatment, may lead to dwarfism. The diagnosis of growth hormone
      deficiency must be suspected very early, sometime at birth, by careful evaluation
      of growth curve which shows marked growth deceleration. Two stimulation tests of
      GH secretion<20 mUI/l are necessary to confirm the diagnosis of GH deficiency in
      order to start treating the patients. MRI of the pituitary gland should be
      realized to diagnose defects in the hypophyseal and hypothalamic structures. Bio
      engineered exogenous GH have very limited side effects and are currently
      prescribed. Administered early in life at adequate dosage, GH replacement therapy
      may significantly increase ultimate adult growth in children with GH deficiency.

PMID- 10970947
TI  - [Pituitary pathology and MEN 1].
AB  - Multiple Endocrine Neoplasia type 1 (MEN 1) is an autosomal dominant syndrome
      characterized by neoplasia of the parathyroid glands, the endocrine pancreas and
      the anterior pituitary gland. Recently the identification on chromosome 11 (locus
      q13) of the gene responsible for MEN 1 has allowed direct genetic diagnosis of
      MEN 1-affected family members. To date almost 300 families have been described
      and genetically characterized. The genetic etiology of most pituitary tumours
      remains unknown. Pituitary adenomas can develop sporadically or as a part of
      multiple endocrine neoplasia type 1. In this review, the recently published data
      on the pathology of the MEN 1 syndrome will be summarized. The clinical,
      morphological and genetic aspects of sporadic and MEN 1-associated pituitary
      adenomas will be outlined.

PMID- 10970948
TI  - [Diagnostic pitfalls in Cushing's disease].
AB  - There are few challenges to an endocrinologist's diagnostic acumen greater than
      the diagnosis of Cushing's disease. In this article, we will review the main
      pitfalls in the diagnosis of Cushing's disease and discuss the value of
      techniques of biochemical and radiological diagnosis.

PMID- 10970949
TI  - [Surgical strategy in Cushing's disease].
AB  - Cushing's disease is almost always due to ACTH hypersecretion by a pituitary
      adenoma. Surgical excision is the only curative treatment. MRI together with ACTH
      assay in the inferior petrous sinus provides the diagnosis and localization in
      80% of cases. Surgery should be wide in all cases, going beyond the limits of the
      adenoma visible on the MRI. Total or subtotal antihypophysectomy may be indicated
      if the imaging is negative and no lateralization can be determined from ACTH
      assays. In case of therapeutic failure, reoperation must be proposed early. A 5
      year follow-up is required before the definitive results of surgery can be
      assessed. Cure is evaluated on the basis of postoperative cortisol levels (<3 - 5
      g/dl). Initially, the rate of remission varies from 70 to 85%. Success after a
      second operation is to the order of 80 to 90%. The surgical risk for ACTH
      adenomas is higher than for other secreting adenomas (CSF fistulae, meningitis,
      thromboembolism, visual disorders), certainly due, in part to subtotal or total
      antihypophysectomy.

PMID- 10970950
TI  - [Acromegaly in 2000].
AB  - Acromegaly is a severe disease often diagnosed late. Morbidity and mortality are
      high, particularly due to cardiovascular and respiratory complications. Clinical
      diagnosis is often difficult to confirm, particularly in ectopic forms. In
      addition, recent reassessment of cure criteria have reduced the number of
      patients considered to be successfully cured. The therapeutic strategy for
      acromegaly is thus changing with the advent of somatostatin agonists. Medical
      treatment is proposed increasingly as the first intention treatment, particularly
      antitumoral therapy for macroadenomas with surgery or radiotherapy being used as
      second line treatment. The recent development of GH analogs offers new
      perspectives for the treatment of acromegaly.

PMID- 10970951
TI  - [Prolactinoma in man: clinical and histological characteristics].
AB  - Prolactinoma usually occurs a small intrasellar tumor in women or as a large
      tumor in men. To determine whether the predominance of macroprolactinomas in men
      is due to a delay in diagnosis as has been suggested, or whether there is a sex
      related difference in growth rate we conducted a retrospective study in 45 men
      and 51 women with prolactinomas. Preoperative prolactin level (PRL) was 2,789 573
      ng/ml and mean tumor size was 26 2 mm. Prolactin levels and tumor size were
      significantly higher in women (292 74 ng/ml and 10 1 mm; p<0.01). There was no
      correlation with age at diagnosis or duration of symptoms. Giant tumors were only
      observed in men (n=8). Frequency of resistance to bromocriptine (30% vs 5%,
      p<0.01) and invasive tumors (52% vs 27%, p<0.001) were significantly higher in
      men than in women. Likewise, proliferation rate was higher for the prolactinomas
      in men (Ki-67: 2.6 1.1% positive nuclei vs 0.4 0.2%; p=0.08; PCNA: 5.0 2.3% vs
      3.7 1.1%). In conclusion, prolactinomas in men are more aggressive than in women.
      They grow rapidly, often invade the cavernous sinus and are resistant to
      bromocriptine; proliferation rates can be increased.

PMID- 10970952
TI  - [Gonadotroph pituitary adenomas].
AB  - Initially, the distinction between "functional" and "non-functional" adenomas was
      a purely clinical notion. A "non-secreting" adenoma was not considered to cause
      acromegaly nor Cushing's syndrome nor amenorrhea-galactorrhea syndrome. The term
      "chromophobe adenoma" has been used since the advent Herlant tetrachrome. More
      recently immunocytochemistry methods have demonstrated that most of the
      "clinically non functional" adenomas (chromophobe with classical histology) are
      actually gonadotrophin secreting adenomas or gonadotroph adenomas. Due to
      progress in immunocytochemistry applied to operated adenomas, it is now known
      that gonadotroph tumors account for 15 to 20% of all pituitary adenomas.
      Gonadotroph adenomas are monoclonal but their pathogenesis, unlike somatotroph
      adenomas causing acromegaly and despite numerous molecular studies, remains
      unknown. Gonadotroph adenomas are most always discovered in patients presenting a
      pituitary syndrome (half to three-quarters consult for a visual field disorder).
      Pituitary imaging almost always demonstrates a macroadenoma: two-thirds of the
      macroadenomas are enclosed. Anterior pituitary insufficiency is much more
      frequent than gonad hyperstimulation whether testicular (macro-orchidia) or
      ovarian (ovarian hyperstimulation similar to that observed in ovulation
      induction). A careful analysis of hormone assay results shows that baseline
      concentrations of gonadotrophin or their free sub-units is elevated in 30 to 50%
      of cases (especially FSH in men, and the free a sub-unit in premenopausal women).
      Dynamic tests contribute little to diagnosis: the GnRH test is positive in 75 to
      100% of cases, the TRH test in 60 to 70% for FSH (or alpha) and when there is
      already a baseline hypersecretion of FSH (or a) in 20 to 30% of the cases for the
      LH when the baseline LH concentration is high. The immunocytochemistry of
      gonadotroph adenomas is slightly different from that of other adenomas:
      generally, only 5 to 10% of the cells, grouped in islets of variable size,
      dispersed in the tumoral parenchyma, bind anti-FH, anti-LH and/or anti-sub-unit a
      antisera. Surgery is the primary treatment for gonadotroph adenomas.
      Complementary radiotherapy may be discussed in case of a postoperative remnant.
      It is probably effective against recurrence. Medical treatment (dopaminergic
      agonists, somatostatin analogs, GnRH agonists and antagonists) have given
      disappointing results.

PMID- 10970953
TI  - [MRI diagnosis of cavernous sinus invasion by pituitary adenomas].
AB  - Several MRI signs are helpful for the preoperative MRI diagnosis of cavernous
      sinus invasion by an adenoma. The first step is to analyse the percentage of
      encasement of the intracavernous ICA by the adenoma. If this percentage is
      greater than or equal to 66%, the cavernous sinus is invaded. If the percentage
      of encasement of intracavernous CA is less than 25%, the cavernous sinus is not
      invaded. If the percentage of encasement is between 25 and 66%, the analysis of
      the cavernous venous compartment, the drawing of intercarotid lines and the
      analysis of the shape and venous compartments of the cavernous sinus are
      necessary. The cavernous sinus invasion remains very likely if the carotid sulcus
      venous compartment is obliterated, or if the lateral intercarotid line is
      crossed. Conversely, if the median intercarotid line is uncrossed, the superior
      venous compartment is visible, the cavernous sinus is of normal size, or there is
      no bulging of its lateral dural wall, invasion of the cavernous sinus space can
      reliably be excluded.

PMID- 10970954
TI  - [Management strategy for type 2 diabetes patients excluding care for
      complications].

PMID- 10970956
TI  - [The XVII Paris symposium neuroradiologicum August 18 - 24, 2002].

PMID- 10970955
TI  - [Biological diagnosis and surveillance of adult hyperthyroidism].

PMID- 10970958
TI  - [ [In Process Citation]

PMID- 10970957
TI  - [What is your diagnosis? Cavernoma].

PMID- 10970959
TI  - Low-dose high-resolution CT of the petrous bone.
AB  - PURPOSE: To show that CT of the petrous bone can be realized using a low-dose
      technique. MATERIAL: and methods: A high-contrast phantom was scanned with 1.5 mm
      slice thickness and 60-510 mAs using the reconstruction algorithms standard, bone
      and edge. In 50 patients, the petrous bone was examined using the standard
      protocol at 510 mAS. Additionally, selected slices were made at 120 or 210 mAs.
      The resolution of relevant structures was compared. Phantom studies were repeated
      on a second CT-device; images of patients scanned with 80 mAs were analyzed in
      regard to resolution of osseous details. RESULTS: With the first CT-device
      structures of the phantom up to 0. 5 mm were depicted using 510 mAs and the edge
      kernel. With 120 mAs and the bone kernel structures of 0.6 mm could be
      distinguished. Although the same resolution was achieved with 60 mAs and the edge
      kernel, patient examinations showed a profound image noise. The results achieved
      with 120 mAs and the bone algorithm, however, were equal to that of 510 mAs. With
      the second device the same image quality was realized with only 80 mAs.
      CONCLUSION: CT-examinations of the petrous bone can be effected without loss of
      diagnostic information using only 15% of the radiation dose used for a standard
      brain examination.

PMID- 10970960
TI  - [Ophthalmic artery, optic nerve and meninges: reciprocal relations].
AB  - The origin of the ophthalmic artery exhibits several variants which can be
      explained by a vascular morphogenesis study. The particular relations of the
      ophthalmic artery with the optic nerve and the cranial meninges are examined
      using serial histological sections.

PMID- 10970961
TI  - [Aspects of FLAIR sequences, 3D-CISS and diffusion-weight MR imaging of
      intracranial epidermoid cysts].
AB  - We propose to assess the usefulness of diffusion-weighted MR Imaging (DWI), fluid
      attenuated inversion recovery (FLAIR) and constructive interference in steady
      state (CISS) sequences in depicting epidermoid cysts (EC). FLAIR, CISS and DWI
      were obtained in 7 patients among 22. All patients were studied with T1 and T2
      sequences. On Spin Echo images, EC demonstrate signal similar to LCS, which may
      lead to difficult differentiation between EC and arachnoid cyst (AC), specially
      for inexperienced radiologists. EC appear with a heterogeneous signal on T1
      images (32%), irregular limits (91%) and with extension through foramen of
      Pacchioni in 18% of cases. On FLAIR sequence, the tumors were heterogeneous,
      different from void signal of CSF in 86% of cases. On CISS sequence, the tumors
      appear heterogeneous, hyperintense but less than LCS and with irregular limits in
      all cases. Some more, CISS images allowed to appreciate exact tumor extension and
      their relations with nerves and vessels. On DWI images, signal is hyperintense in
      all cases. Our study exhibited the great usefulness of DWI, CISS and FLAIR
      sequences in diagnosis of EC and in differentiating EC from AC.

PMID- 10970962
TI  - [MR imaging in the diagnosis of intradural extramedullary tuberculoma. Report of
      a case and review of the literature].
AB  - Intradural extramedullary tuberculoma without any bony involvement is
      exceptional. Nineteen cases were found in the literature. We report the case of 5
      year-old boy who presented acute paraplegia 8 months after a tuberculous
      meningitis under antituberculous treatment. Dorsal gadolinium enhanced MRI
      revealed an intradural extramedullary bunch-shaped enhancing mass at T5-T6 level.
      The tuberculous nature was confirmed by histology after surgical removal of the
      lesion followed by a good recovery. To our knowledge, this is the first
      intradural extramedullary tuberculoma detected by MRI. We underline the role of
      MRI in the diagnosis of this particular localisation of tuberculosis.

PMID- 10970963
TI  - MRI detection of olfactory bulb and tract.
AB  - Thirty healthy volunteers underwent MRI with 3D MP-RAGE, 3D CISS and 2D turbo
      spin echo sequences to compare the detectability of olfactory fibers, bulb,
      tract, and sulcus. The overall detectability was slightly better using MP-RAGE
      compared with CISS. Both 3D sequences were superior to 2D turbo spin echo. We
      therefore recommend including the MP-RAGE sequence in an MR imaging protocol of
      the olfactory nerve.

PMID- 10970965
TI  - [Spiral CT evaluation of the craniosynostoses].
AB  - Craniosynostoses are defined as the premature closure of one or more sutures of
      the cranial bones. The resulting craniofacial deformities may be associated with
      neurologic complications owing to the disproportion between the growing brain and
      the limited content of the intracranial cavity. Plain skull radiographs are often
      contributive to the diagnosis. However, they may not be sufficient to detect
      early cases and to properly evaluate the more complex cases. Computed tomography
      has been proved to be more efficient in the pretherapeutic evaluation. The
      authors present here their results in the spiral computed tomographic evaluation
      of primary and syndromic craniosynostosis, based on a prospective series of 26
      patients. The radiologic findings are presented. They have been found here to be
      similar to those previously described on sequential acquisitions. Spiral computed
      tomography was found to provide better information than did plain radiographs in
      5 cases. The value of the helical acquisition as well as tridimensional
      reconstructions are discussed.

PMID- 10970964
TI  - [Degree of hemodynamic disturbance at the hyperacute phase of stroke: predictive
      value of 3D-TOF angiography and the T2 fast-FLAIR sequence].
AB  - GOAL: To define during the hyperacute phase of stroke the value of 3D-TOF MR
      angiography (MRA) and T2 fast-FLAIR sequence for predicting the volume of tissue
      presenting a hemodynamic disturbance. MATERIAL: and method: Thirty-five cases of
      hyperacute stroke located in following territories: middle cerebral artery (MCA)
      (n=29), anterior choroidal artery (AChoA) (n=5) and watershed (n=1) were
      retrospectively reviewed. The vascular abnormalities defined on MRA (vessel
      stenosis or occlusion) or FLAIR sequence (vessel hyperintensity) were classified
      into 3 groups: normal (I), distal abnormalities (II), abnormalities of the entire
      arterial territory (III). These results were compared with the volume of tissue
      showing a prolonged mean transit time (MTT) determined on relative MTT maps
      calculated from bolus tracking MR perfusion images. RESULTS: The abnormal volume
      measured on the MTT map was significantly correlated to the results of the MRA
      and FLAIR sequence. In the 12 cases of group III defined on the MRA (abnormality
      from M1), the volume of hemodynamic disturbance was always higher than 100 ml.
      For the MCA territory, it was not possible to predict the presence of a
      hemodynamic disturbance in any of the 3 groups defined on the FLAIR sequence and
      in the groups I and II defined on the MRA. For the AChoA territory, a hemodynamic
      disturbance was never observed in groups I and II defined either on MRA or FLAIR
      sequence. CONCLUSION: When there was no flow within the M1 segment on the MRA,
      there was always a hemodynamic disturbance larger than 100 ml on the MTT map. In
      the case of AChoA ischemic lesion, when no vascular abnormality was observed on
      the MRA or FLAIR images, the MTT map was always normal.

PMID- 10970966
TI  - [Cavernous sinus dermoid cyst with unusual parapharyngeal development].
AB  - We report a case of dermoid cyst arising in the cavernous sinus and
      parapharyngium areas through the foramen lacerum. A 12-year-old girl was
      hospitalized in October 1966 for progressive intracranial hypertension. CT before
      a prior surgical intervention in 1994 showed an intracranial process suggesting a
      dermoid cyst. CT performed in October 1996 showed a temporal process at the left
      side measuring 8 cm x 5 cm and well circumscribed with a thin wall. This process
      extended towards the parapharyngium area through the foramen lacerum. The
      exocranial part measured 4 cm in diameter. The density of the process strongly
      suggested a mature dermoid cyst with fatty and calcium components. The histology
      study confirmed the diagnosis of dermoid cyst. The frequency of intracranial
      dermoid cysts is 2 to 3 times less than that of epidermoid cysts. This is an
      uncommon process accounting for 1% of intracranial tumors occurring in children.
      In the sustentorial spaces, the process occurs more frequently in the parasellar
      area. To our knowledge, exocranial extension has not been reported to date.

PMID- 10970967
TI  - [Sub-occipital Pott's disease. Diagnostic imaging in 2 cases].
AB  - Pott's disease is the most common form of bone and joint tuberculosis, notably in
      the thoracolumbar spine. The sub-occipital localization remains exceptional,
      raising a major risk of spinal instability and severe bulbo-medullary
      complications. We report 2 new cases of tuberculous spondylodiscitis at the
      cervico-occipital junction revealed by signs of spinal compression associated
      with torticolis and dysphagia. The diagnosis was provided by CT scan and MR
      imaging and was confirmed histologically on a transoral biopsy of the
      retropharyngeal abscess. The patients were successfully treated with
      antituberculosis drugs combined with external stabilization of the spine. The
      diagnostic aspects, notably the neuroradiological findings in this particular
      localization of Pott's disease are recalled.

PMID- 10970968
TI  - [Segmental instrumentation in idiopathic scoliosis. Role of the upright frontal
      plate for determination of the area of fusion].
AB  - PURPOSE OF THE STUDY: To analyze post operative imbalance after C.D.I. (Cotrel
      Dubousset Instrumentation) for idiopathic scoliosis according to the fused area,
      particularly the lower level of fusion. To recall a classification for
      determination of fusion area based on preoperative standing coronal radiograph.
      PATIENTS AND METHODS: To be included in this study the patients had to have an
      adolescent idiopathic scoliosis, at least two years of post operative follow up.
      122 patients met the criteria; mean follow up was 3 years, 5 months (minimum 2
      years, maximum 9 years). Scoliotic curves were classified as single structural
      (81), double structural (41). Balance was clinically analyzed by plumbline,
      radiographically by a plumbline dropped from C7 to the sacrum and measuring
      deviation from the midpoint of the sacrum in centimeters. A curve with a
      deviation of 10 mms or less was considered as balanced. RESULTS: Imbalance in
      single structural curves was 70% when using stable vertebra (King) or "other
      vertebra" (beyond stable vertebra or one or two levels upper stable vertebra).
      Using end vertebra (J. Moe), (elected vertebra - C. Salanova) imbalance was 10%.
      In double structural (41 cas) imbalance was 50% using stable, or "other vertebra"
      10% when elected vertebra was fused. DISCUSSION: In this study there was a strong
      relationship between the lower level of fusion and imbalance.

PMID- 10970969
TI  - [Role of osteosynthesis in the consolidation of posterolateral arthrodesis: a
      comparative study in patients operated for lumbar stenosis].
AB  - PURPOSE OF THE STUDY: The main objective of this work was to determine the impact
      of osteosynthesis for posterolateral arthodesis on bone consolidation. We also
      tried to isolate factors predictive of nonunion and the effect of nonunion on the
      final outcome. MATERIAL AND METHODS: We recaIIed for assessment patients who had
      undergone surgery for stenosis of the lumbar spine and who had a posterolateral
      lumbar or lumbosacral arthodesis in addition to the spinal decompression. Among a
      total of 98 operated patients, 31 had arthrodesis without instrumentation. These
      31 patients were matched for age, sex, smoking habits, and extent of the fusion
      with 31 other patients who had an instrumented arthrodesis. Radiological and
      clinical assessment obtained preoperatively and at 6, 12, and 24 months
      postoperatively were available for all 62 patients. RESULTS: Our two groups of
      patients were similar for comorbidity, number of arthodesis levels, fusion zone,
      extent and site of associated radicular release, lumbar lordosis, slope of the
      sacrum, global spinal mobility, and angular anteroposterior intersegmentary
      mobility of the different levels of the fusion zone, and interertebral sliding
      (site, degree, type, ante- or retrolisthesis). At last follow-up, rate of
      malunion was the same in the two groups (35 p. 100). Statistical analysis
      demonstrated three factors significantly associated with malunion:
      anteroposterior intersegmentary mobility, and especially angular mobility and
      disk height. Disk height was not however significant if it was associated with
      intersegmentary hypermobility. Other parameters studied, and notably use of
      ostheosynthesis material or not, preoperative comorbility, presence or not of
      preoperative intervertebral displacement, and level of the arthrodesis, had no
      effect. DISCUSSION: Considering the type of arthrodesis studied (short fusion on
      a globally minimally mobile spine) the series demonstrated that the use of
      osteosynthesis material does not significantly increase the rate of fusion of
      posterolateral arthrodesis and that the mobility of the spinal segment involved
      is probably a more important predictive factor for the quality of the fusion.

PMID- 10970970
TI  - [Quality of life assessment one year after total hip or knee arthroplasty].
AB  - PURPOSE OF THE STUDY: The development of quality of life (QOL) instruments has
      made it possible to obtain an objective assessment of the impact of surgical
      procedures taking into consideration the physical, psychological and social
      aspects of the patient's everyday activities. The aim of this work was to
      evaluate the short-term and long-term course of QOL after total hip arthroplasty
      (THA) and total knee arthroplasty (TKA). MATERIALS AND METHODS: This study
      included a prospective multicentric cohort of patients with a first intention
      indication for degenerative bone and joint disease. Clinical assessment was
      obtained preoperatively and 6 weeks, 6 months and 12 months postoperatively. The
      Merle d'Aubigne and Harris scores were determined for THA and the Hospital
      Special Surgery score for TKA. Clinical data (pain, walking distance), and QOL
      scores [French version of the Nottingham Health Profile (NHP) and the French
      version of the Arthritis Impact Measurement Scale 2 (AIMS2)] were also obtained.
      RESULTS: One hundred twenty-three patients had a THA (mean age 62 years) and 60
      had a TKA (mean age 68 years). Preoperative clinical features were those commonly
      found in these populations. For THA, the 6-week, 6-month and 1-year assessments
      showed an improvement (2.7 and 2.8 points on the 0 to 10 NHP). For TKA,
      improvement came later and was less significant with 0.8, 1.8 and 1.5 point
      improvements. The AIMS 2 did not appear to be perfectly adapted to measure this
      dimension. Improvement in pain came earlier and was greater for THA than for TKA
      on all measurement scales. For THA, psychological capacity improved by 0.7, 1.4
      and 1.5 points on the 0 to 10 AIMS 2 at 6 weeks, 6 months and 12 months
      respectively. For TKA, improvement was to the same order with 1.1 and 1.2 point
      improvements at 6 weeks and 6 months respectively. DISCUSSION: These findings
      confirm the clear improvement in QOL after THA and TKA, mainly due to physical
      and psychological dimensions. The QOL measurements allow comparisons with other
      surgical procedures in other fields. They provide supplementary information,
      notably concerning pain and are particularly useful in orthopedic surgery. The
      questionnaires are generally well accepted by the patients, particularly short
      self-administered questionnaires. They provide useful information on the efficacy
      of THA and TKA in terms of human and social costs and open new perspectives for
      analysis of prognostic factors for optimal QOL of operated patients.

PMID- 10970971
TI  - [Cementless acetabular fixation with solid alumina sockets. Apropos of 62 total
      hybrid prostheses with press-fit alumina sockets at 6-year mean follow-up].
AB  - PURPOSE OF THE STUDY: In order to avoid polyethylene wear observed in total hip
      replacement, an alumina-alumina combination has been used since 1977. The aim of
      this prospective study was to assess the results of an alumina-alumina total hip
      arthroplasty with a cementless press-fit plain alumina socket and a cemented
      titanium alloy stem with special attention for socket fixation because of
      previously encountered problems. MATERIALS AND METHODS: Fifty-five patients (62
      hips) were operated on between 1982 and 1990. The main parameter for inclusion
      was a high level activity demand. The bearing surfaces were a 32 mm alumina head
      articulating within the alumina socket. Mean follow-up was 6 years. RESULTS: Four
      revisions occurred in this series: 3 for aseptic loosenings of the socket and 1
      for femoral head fracture. Considering acetabular revision for aseptic loosening
      as the end point, the survival rate was 93.2 % at six years and 78.8 % at six
      years when considering acetabular loosening as the end point. At a mean of 72.1
      month-follow-up, 92.4 % of the remaining hips were graded as very good or good
      while 44.6 % showed radiolucent lines around the socket and 4 had migrated with
      no radio-clinical correlation. On the femoral side, there was no radiolucent line
      nor loosening, and the value of the colar calcar resorption was low (mean 0.4
      mm). In all four revisions, the stem was left in place, and there was no bone
      loss, which allowed simple revisions. DISCUSSION: Thin radiolucent lines around
      bulk alumina press-fit sockets can be understood as a normal bone reaction to
      material as the Young's modulus is much higher. They do not necessarily signify
      mechanical failure of the fixation. However when considering the rate of
      acetabular loosening, an improvement of the alumina/bone interface is still
      required.

PMID- 10970972
TI  - [Arthroscopic assessment and clinical correlation of femoro-patellar tracking.
      Apropos of 116 knees in 115 patients under 40].
AB  - PURPOSE OF THE STUDY: The dynamic study of the patello-femoral joint is of
      outstanding interest in unexplained anterior knee pain syndrome. Accuracy of
      information provided by video-arthroscopy is of concern due to its technical
      conditions. Serum inflow favors the natural patellar tendency to shift laterally
      (mean value, 7 degrees ). Absence of active quadriceps muscle contraction under
      anesthesia and use of a tourniquet act conversely. The aim of this study
      conducted in less than 40 year-old patients, was to correlate retrospectively
      arthroscopic evaluation of patello-femoral tracking and trochlear centralization
      measured during conventional "inflow" procedure, with patella related pain
      syndrome and its outcome. MATERIAL AND METHODS: The study group included 116
      knees in 66 male and 49 female patients (1 bilateral). Mean age at arthroscopy
      was 26 years (range, 12 to 40 years). According to pre-arthroscopic clinical
      data, knees were broken down into 3 study groups: Gr-T (Test, painless patella),
      50 knees with meniscal and/or ligament injury: Gr-PRP (Patella Related Pain but
      no dislocation), 55 knees: Gr-DLC (patella DisLoCation), 11 knees. Arthroscopic
      technique was the following: general anesthesia, high-proximal pneumatic
      tourniquet (40mmHg), single antero-lateral portal and serum inflow by simple
      gravity (2m). The minimum flexion angle that was necessary to obtain de visu a
      perfect centralization of the patella dome into the trochlear groove was
      systematically measured before any arthroscopic procedure was performed. RESULTS:
      Average value of the Flexion Angle providing perfect Centralization (FAC) in the
      "serum inflow" arthroscopic situation was 39 degrees in Gr-T and 52 degrees in Gr
      PRP; this difference was highly significant (p <.0001). Patella centralization
      could not be achieved despite maximum possible flexion in 5 of the 55 PRP-knees
      and in 9 of the 11 DLC-knees. FAC value > 65 degrees correlated significantly
      (chi2, p=0.0001) with patella related clinical symptoms (pain and instability,
      groups PRP + DLC) and indicated patellar maltracking. In the PRP-group, an "FAC
      value > 65 degrees" showed a low sensitivity (0.34), but high specificity and
      positive predictive value of 0.98 and 0.95, respectively. DISCUSSION AND
      CONCLUSION: Arthroscopic examination for patello-femoral tracking can provide
      measurable information on the FAC angle, that is reproducible under precise
      technical conditions. Its diagnostic value in unexplained anterior knee pain
      versus information provided by conventional imaging, and their respective
      effectiveness-risk and -cost relations could be the purpose of future prospective
      studies.

PMID- 10970973
TI  - [False iatrogenic aneurysm complicating septic malunion of the femur].
AB  - We report a case of false iatrogenic aneurism of the femoral artery observed
      after external fixation for septic malunion of the femur subsequent to emergency
      plate fixation. This false aneurysm ruptured, requiring femoropopliteal arterial
      repair. In the septic context, the vascular sutures failed making it necessary to
      ligature the femoral artery. Vascularization was maintained by satisfactory
      collateral circulation.

PMID- 10970975
TI  - [Subacute osteomyelitis in adults. Apropos of 3 cases].
AB  - We report three cases of subacute osteomyelitis in 25, 31 and 38-year old adults.
      The clinical presentation was an insidious condition with persistent nondisabling
      pain. Radiographical signs suggested a bone tumor. Diagnosis was established from
      the bacteriological and pathology examinations of the surgical biopsy taken when
      evacuating the abscess. Cure was obtained in all three patients with combination
      antibiotic regimens. In two cases immobilisation was required because of bone
      fragility.

PMID- 10970974
TI  - [Rupture of the patellar ligament one month after treatment with
      fluoroquinolone].
AB  - Musculoskeletal disorders including arthralgia and myalgia are adverse effect
      common to all fluoroquinolones. We report a case of spontaneous rupture of the
      patellar ligament in a 37-year-old man participating in leisure sports which
      occurred one month after a three-week course of Ciprofloxacine(R). Several cases
      of tendon ruptures have been reported in the literature, including the patellar
      tendon. Unusual features in our case were the one-month delay before tendon
      rupture and the absence of inaugural signs. We reviewed the pathophysiological
      mechanisms leading to fluoroquinolone-related tendon rupture as well as the risk
      factors and discussed proper management. Care must be taken when prescribing
      fluoroquinolones for patients at risk. Close follow-up is most important.

PMID- 10970976
TI  - Insulin-like growth factor I correlates with protein intake estimated from the
      normalized protein catabolic rate in hemodialysis patients.
AB  - BACKGROUND/AIM: Malnutrition and catabolism are predominant problems in patients
      undergoing hemodialysis. The aim of this study was to clarify the relationship
      between insulin-like growth factor I (IGF-I), the serum levels of which are
      influenced by nutrition and which by itself promotes amino acid uptake, and
      insulin-like growth factor binding protein 1 (IGFBP-1), known to regulate serum
      (s) IGF-I and protein intake, in end-stage renal disease patients. METHODS:
      Thirty hemodialysis patients were studied, and s-IGF-I and s-IGFBP-1 levels were
      measured by radioimmunoassay. The s-IGF-I method used was validated according to
      a reference method. The s-IGF-I standard deviation (SD) score was calculated,
      giving the individual deviation from the mean of a reference population. The
      protein intake was estimated both directly by 3-day food recall by a dietician
      and indirectly by normalized protein catabolic rate (PCRn). RESULTS: The mean
      serum IGF-I level was 166 +/- 10 microgr;g/l, corresponding to a normal s-IGF-I
      SD score (0.5 +/- 0.3). S-IGFBP-1 was elevated threefold to 101 +/- 11 microg/l
      as compared with normal subjects. The s-albumin was 39.9 +/- 0.5 g/l and the s
      bicarbonate 24 +/- 0.4 mmol/l. There were significant correlations between s-IGF
      I SD score or s-IGF-I (log-transformed) and PCRn (r = 0.37, p < 0.004, and r =
      0.41, p < 0.001, respectively). The s-IGF-I/s-IGFBP-1 ratio was also positively
      correlated with PCRn (r(s) = 0.36, p < 0.007, by Spearman's rank correlation).
      The s-albumin was inversely correlated with log s-IGFBP-1 (r = -0.38, p < 0.01)
      and positively with the s-IGF-I/s-IGFBP-1 ratio (r = 0.36, p < 0.007) but not
      with s-IGF-I (p < 0.13). Serum total cholesterol, triglycerides, and total body
      fat as percentage of body weight correlated with s-IGF-I (r = 0.47, p < 0.004, r
      = 0.45, p < 0.01, and r = 0.42, p < 0.004, respectively) as well as with the s
      IGF-I SD score. No correlations were seen between s-IGF-I and protein or caloric
      intake by direct estimates from dietary food recalls. CONCLUSIONS: The s-IGF-I
      and the s-IGF-I/s-IGFBP-1 ratio were correlated with estimates of protein intake
      of the patients calculated from urea kinetics (PCRn) but not with direct
      estimates by the dietitian. The s-IGF-I SD score and the ratio s-IGF-I/s-IGFBP-1
      might be a tool to monitor anabolic status and to select hemodialysis patients
      for therapeutic intervention with recombinant human IGF-I and/or recombinant
      human growth hormone to counteract catabolism.

PMID- 10970977
TI  - The evaluation of corticosteroid therapy in conjunction with plasma exchange in
      the treatment of renal cholesterol embolic disease. A report of 5 cases.
AB  - In this report, we describe 5 patients with cholesterol atheroembolic renal
      failure. In 3 of the 5 patients, combined therapy with corticosteroids and plasma
      exchange was performed. These 3 patients survived, with 2 showing an improvement
      in renal function. The 2 remaining patients died of multifactorial causes. The
      literature on therapy for cholesterol atheroembolic renal failure is reviewed and
      the efficacy of combined therapy by use of corticosteroids and plasma exchange is
      evaluated.

PMID- 10970978
TI  - Predictors of the development of hyperkalemia in patients using angiotensin
      converting enzyme inhibitors.
AB  - BACKGROUND/AIMS: Angiotensin-converting enzyme inhibitors (ACEI) are the
      antihypertensives of choice in patients with chronic renal failure (CRF). ACEI by
      decreasing the synthesis of aldosterone, the main regulator of serum potassium,
      predispose to the development of hyperkalemia. Although hyperkalemia with
      administration of ACEI is uncommon in patients with a normal renal function, a
      preexisting abnormality in potassium hemostasis, as seen in patients with chronic
      renal failure, may increase the risk of hyperkalemia. METHOD: To determine the
      predictors of development of hyperkalemia (K >5.1 mEq/l) in patients on ACEI, we
      retrospectively reviewed medical records of 119 patients followed in our renal
      clinic. RESULTS: The mean age of the patients was 56 +/- (SD) 13 (range 20-84)
      years. Sixty-three percent were males, and 37% were females. Sixty-seven percent
      had a history of diabetes. Eighty five percent of the patients had CRF
      [creatinine clearance (CrCl) <80 ml/min]. The baseline serum Cr was 2.3 +/- 1.2
      (range 0.6-6.9) mg/dl, and the CrCl was 50 +/- 27.5 ml/min. Of the 119 patients
      46 (38.6%) developed hyperkalemia (mean K 5.68 +/- 0.3, range 5.2-6.7 mEq/l).
      Ninety-six percent of the patients who developed hyperkalemia had CRF, and 84%
      were diabetics. Pearson product-moment correlation revealed a significant
      positive correlation of hyperkalemia with Cr and a negative correlation of
      hyperkalemia with CrCl and HCO(3) (Cr: r = 0.42, p < 0.0001; CrCl: r = -0.34, p <
      0.0001; HCO(3): r = -0.41, p < 0.0001). Multivariate logistic regression analysis
      revealed diabetes and serum creatinine to be the main predictors of hyperkalemia.
      In 31 patients hyperkalemia resolved either with a low-potassium (2 g/day) diet
      or with diet and a decrease in the dose of ACEI. In 15 patients ACEI had to be
      discontinued due to persistent hyperkalemia. CONCLUSIONS: We conclude that
      hyperkalemia is common in patients with CRF on ACEI. The majority of the patients
      who develop hyperkalemia on ACEI have CRF and diabetes. A large number of
      patients with CRF require discontinuation of ACEI due to hyperkalemia and are
      deprived of their renoprotective effects.

PMID- 10970979
TI  - Diagnosis and treatment of tuberculosis in hemodialysis and renal transplant
      patients.
AB  - BACKGROUND: The incidence of Mycobacterium tuberculosis in hemodialysis (HD) and
      renal transplant (RT) patients in developing countries is high. With the
      resurgence of tuberculosis in the US, insights gained in the diagnosis and
      treatment of this infection in HD and RT patients in developing countries should
      be valuable to physicians in the West. METHODS: A retrospective study of 40 cases
      of tuberculosis, 24 in HD patients (24/177, 13.6%) and 16 in RT patients (16/109,
      14.7%) diagnosed over a period of 21 months in one center. RESULTS: The clinical
      features, diagnostic procedures, and management dilemmas of this group of
      patients are described in this report. Diabetes mellitus was the most common
      associated disease in both groups of patients. Fever, the most common presenting
      sign, was persistent low grade in 66.6% of HD patients and high intermittent in
      56.2% of RT patients. Fever of unknown origin was only seen in RT patients.
      Pulmonary involvement was most common in both groups, presenting either as
      infiltrates or effusions. Tuberculous peritonitis was seen only in HD patients
      (33.3%). Eight HD patients were treated for tuberculosis for variable periods
      prior to transplantation, 4 of whom had less than 6 months of therapy. None had a
      recurrence of tuberculosis after transplantation. Because of the known
      cyclosporin-lowering effect of rifampicin resulting in an increased cost of
      immunosuppressive therapy, 13 patients were treated successfully with rifampicin
      sparing therapy. CONCLUSION: Tuberculosis should be included in the differential
      diagnosis of fever in HD and RT patients, especially if fever is of unknown
      origin in the RT patient. M. tuberculosis in the renal transplant patient can
      present with high intermittent fever. Partial treatment of tuberculosis is
      sufficient prior to renal transplantation but treatment should be continued to
      completion after transplantation. If the cost of immunosuppressive therapy is
      prohibitive because of rifampicin, rifampicin-sparing antituberculosis therapy
      can be successfully employed in RT patients.

PMID- 10970980
TI  - Detection of cardiac calcinosis in hemodialysis patients by whole-body
      scintigraphy with 99m-technetium methylene diphosphonate.
AB  - A noninvasive method for the diagnosis of cardiac calcinosis, a life-threatening
      complication in hemodialysis patients with end-stage renal disease (ESRD), has
      not, as yet, been firmly established. We tested whether whole body scanning with
      99m-technetium methylene diphosphonate (MDP) might visualize cardiac calcinosis.
      In 19 consecutive chronic hemodialysis ESRD patients (13 males and 6 females,
      aged 40-81, mean 63 +/- 8 years) with cardiovascular disease [mitral annular
      calcinosis and/or calcified aortic valve (n = 4), hemodialysis cardiomyopathy (n
      = 1), coronary artery disease (n = 9) and peripheral artery atherosclerotic
      disease (n = 6)], MDP uptake in the heart was compared to that in 7 non-ESRD
      controls with hyperparathyroidism due to adenoma. Cardiac and lung field MDP
      uptake was confirmed in only 3 (16%) and 5 (26%) of the 19 ESRD subjects,
      respectively, but was absent in controls. Positive cardiac uptake was related to
      cardiac calcified complications (mobile intracardiac calcinosis, myocardial
      calcinosis and mitral annular calcification) and the duration of hemodialysis (p
      = 0.015). While it was statistically insignificant, subjects showing MDP uptake
      were elder and had higher serum Ca or Ca x P product and lower intact parathyroid
      hormone levels. These results suggest that cardiac calcinosis in ESRD patients
      can be detected noninvasively by myocardial scintigraphy with 99m-technetium MDP.

PMID- 10970981
TI  - Urinary deoxypyridinoline excretion for the evaluation of bone turnover in
      chronic renal failure.
AB  - BACKGROUND: The urinary excretion of deoxypyridinoline (DPD) was evaluated in
      predialysis chronic renal failure (CRF), together with intact PTH and several
      classic markers of bone turnover in order to assess whether urine free and total
      DPD excretion are equivalent parameters of bone turnover in CRF, and to evaluate
      the relationship between urine DPD excretion, PTH and the other bone markers.
      METHODS: The study was carried out in 94 patients with different degrees of renal
      failure due to various kidney diseases. Besides urinary DPD expressed as free
      DPD, total DPD, free/total DPD, free DPD/Cr and total DPD/Cr, the following
      determinations were made: intact PTH, bone alkaline phosphatase (BALP), total
      alkaline phosphatase (AP), osteocalcin (BGP), serum C-terminal telopeptide of
      collagen type I (ICTP) and hydroxyproline (OHpro). The patients were divided into
      3 groups according to the increasing severity of renal failure (Ccr >40, 40-20,
      <20 ml/min). RESULTS: The ratio free/total DPD decreased (NS) with advancing
      renal failure, and was inversely correlated with total DPD excretion. While PTH
      increased progressively to about four times the values observed in the Ccr >40
      group, there was a parallel increase only in BGP and ICTP, parameters retained in
      the serum with decreasing renal function, while AP, BALP, total DPD and OHpro did
      not change. However, significant correlations between total DPD/Cr and PTH, BALP,
      BGP and ICTP were also found. CONCLUSIONS: In CRF free DPD is an unreliable index
      of bone turnover due to a probable interference in its production from the
      peptide-bound DPD. Total DPD or total DPD/Cr are better used. In spite of the
      significant correlations observed in advanced renal failure between PTH and most
      of the parameters examined, a resistance of bone tissue to PTH action in CRF must
      be considered.

PMID- 10970982
TI  - Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of
      human glomerular diseases.
AB  - We investigated the presence of CCR1- and CCR5-positive cells
      immunohistochemically in the kidneys of 38 patients with several renal diseases,
      including 13 crescentic glomerulonephritis patients. In addition, we determined
      cell phenotypes of CCR1- and CCR5-positive cells using a dual immunostaining
      technique. Urinary levels of their ligands, for CCR1 and CCR5; macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation in
      normal T cells expressed and secreted (RANTES) were evaluated by enzyme-linked
      immunosorbent assay. CCR1- and CCR5-positive cells were detected in both
      glomeruli and interstitium of the diseased kidneys. Using a dual immunostaining
      technique, these positive cells were CD68-positive macrophages (MPhi) and CD3
      positive T cells. The number of CCR1-positive cells in glomeruli was correlated
      with urinary levels of MIP-1alpha. The number of CCR1-positive cells in the
      interstitium was correlated with both urinary MIP-1alpha and RANTES levels. CCR1
      positive cells in the interstitium remained after glucocorticoid therapy, most of
      which were MPhi, and were correlated with the intensity of interstitial fibrosis
      and tubular atrophy. Glomerular CCR5-positive cells were well correlated with
      extracapillary lesions and urinary MIP-1alpha levels, while interstitial CCR5
      positive cells, mainly CD3-positive T cells, were correlated with interstitial
      lesions and urinary RANTES levels. Renal CCR5-positive cells were dramatically
      decreased during convalescence induced by glucocorticoids. These results suggest
      that chemokine receptor signaling may be pivotal for human renal diseases through
      the recruitment and activation of MPhi and T cells; CCR5-positive cells may
      participate in glomerular lesions including extracapillary lesions via MIP-1alpha
      and in interstitial lesions via RANTES. CCR1 may be involved in interstitial
      lesions in resolving phase after glucocorticoid therapy.

PMID- 10970983
TI  - Influence of dialysis procedure, membrane surface and membrane material on
      iopromide elimination in patients with reduced kidney function.
AB  - Haemodialysis for the elimination of contrast medium in patients with advanced
      renal failure is a common procedure. Even though sufficient elimination with the
      use of regular low-flux membranes is documented, large differences in results
      have been reported in prior investigations. We, therefore, compared Cuprophan and
      polysulfone dialysers with different surface areas to haemofiltration with
      different amounts of substitution fluid in 40 patients with compromised renal
      function after coronary angiography. Plasma iodine concentrations were measured
      by fluorescent excitation analysis. At constant blood flow rates of 200 ml/min,
      Cuprophan membranes with 1. 3 m(2) surface area had a clearance rate of 87
      ml/min, whereas polysulfone membranes of comparable size displayed a
      significantly higher clearance rate of 147 ml/min. Polysulfone membranes with 1.8
      m(2) surface area showed a small but insignificant increase in the iodine
      clearance (162 ml/min), while Cuprophan membranes displayed an increase in
      clearance rates (121 ml/min). Additional ultrafiltration led to a further
      increase in the plasma clearance of both membranes and reduced urinary iodine
      excretion. Haemofiltration was comparable to haemodialysis in terms of efficacy
      and thus represents an alternative method. Clearance of iopromide during
      haemodialysis with polysulfone membranes is higher than with Cuprophan membranes.
      Elimination rates can be further increased by additional ultrafiltration.
      Haemofiltration is comparable to haemodialysis regarding contrast medium
      elimination.

PMID- 10970984
TI  - G-Protein beta(3) subunit C825T variant, nephropathy and hypertension in patients
      with type 2 (Non-insulin-dependent) diabetes mellitus.
AB  - BACKGROUND: There is substantial evidence that hereditary factors contribute to
      the predisposition to diabetic nephropathy. On the other hand, it has been
      suggested that genetics of diabetic nephropathy and hypertension may overlap.
      Recently, a C to T substitution (C825T) in the gene encoding for the guanine
      nucleotide-binding protein beta(3) subunit (GNB3) was identified, and this
      molecular variant was found to be associated with enhanced activation of G
      proteins and increased risk of the development of hypertension. The aim of the
      study was to test whether GNB3 C825T polymorphism contributes to the development
      of incipient or overt nephropathy or hypertension in type 2 diabetic patients.
      METHODS: GNB3 genotype was determined in 130 type 2 diabetic patients with overt
      proteinuria or chronic renal failure, 155 diabetic patients with microalbuminuria
      and 163 control subjects with normoalbuminuria and known type 2 diabetes duration
      of at least 10 years. RESULTS: No differences in GNB3 genotype distributions or
      allele frequencies between the study groups were found. Also, no differences
      between normotensive and hypertensive patients were demonstrated. CONCLUSION: The
      study provided evidence against the major impact of the GNB3 C825T polymorphism
      on the increased risk of the development of nephropathy or hypertension in type 2
      diabetic patients.

PMID- 10970985
TI  - Comparison of vector and conventional bioelectrical impedance analysis in the
      optimal dry weight prescription in hemodialysis.
AB  - BACKGROUND: Dry weight prescription is commonly based on symptoms induced by
      inappropriate fluid removal by hemodialysis (HD). Aim of this study was to
      compare the assessment of volume status by conventional bioelectrical impedance
      analysis (BIA) and the resistance-reactance (RXc) graph method in HD patients
      achieving their target dry weight determined on clinical criteria. METHODS: We
      studied 39 HD patients (23 males and 16 females, mean age 52 +/- 17 years,
      dialytic age 41.2 +/- 37 months). Dry weight, prescribed according to the
      standard clinical criteria, was constantly achieved in the last 3 months.
      Patients symptom-free over the last 3 months were defined as asymptomatic.
      Patients with either muscular cramps or hypotensive episodes were defined as
      symptomatic. Thirty-three healthy volunteers (11 males, 22 females, mean age 50
      +/- 11 years) constituted the control group. Standard, single frequency (50 kHz),
      tetrapolar, BIA measurements were obtained in controls, and in patients before,
      every 60 min, and 30 min after one HD session. Total body water (TBW), and
      extracellular water (ECW) were calculated using conventional BIA regression
      equations. In both groups, tissue hydration was also assessed by the RXc graph
      method. RESULTS: On the basis of 95% tolerance interval (mean +/- 2 SD) for the
      ECW (%) calculated in healthy subjects (ECW = 35-44%), HD patients were divided
      into 3 groups according to their post-HD ECW: 72% normohydrated with ECW 35-44%,
      10% overhydrated with ECW >44%, and 18% underhydrated with ECW <35%. Patients
      were also classified into 3 categories according to the RXc graph method: 38%
      normohydrated with vectors within the reference 75% tolerance ellipse, 0%
      overhydrated with short vectors below the lower pole of the 75% tolerance
      ellipse, and 62% underhydrated with long vectors above the upper pole of the 75%
      tolerance ellipse. The progressive removal of body fluid during HD treatment was
      associated with a progressive increase in both impedance vector components, R and
      Xc. Eleven of thirty-nine patients (28%) were symptomatic during HD treatment in
      the last 3 months. The majority of these (73%) were classified as normohydrated
      according to ECW estimates, while 9 and 18% were classified as over- and
      underhydrated, respectively. This frequency distribution was significantly
      different from that obtained with the RXc graph method (chi(2) = 6.9, p = 0.03)
      where the majority (73%) were classified as underhydrated, while 0 and 27% were
      classified as over- and normohydrated, respectively. The frequency distribution
      of the 28 asymptomatic patients also significantly differed between conventional
      BIA and RXc graph hydration categories (chi(2) = 10.8, p = 0.005), since 11, 71
      and 18% vs. 0, 43 and 57% of patients were classified as over-, normo-, and
      underhydrated, respectively. CONCLUSIONS: The classification of volume status
      based on conventional BIA was insensitive to either clinical situation (presence
      or absence of symptoms). In contrast, the classification based on the RXc graph
      was consistent with the clinical course in symptomatic patients (73% dehydrated,
      and 27% normohydrated), while it did not reflect the clinical course in
      asymptomatic patients, 57% of whom were classified as (already) underhydrated. A
      longitudinal study will establish the clinical usefulness of RXc graph
      indications in asymptomatic patients.

PMID- 10970986
TI  - Comparison of blood gas and acid-base measurements in arterial and venous blood
      samples in patients with uremic acidosis and diabetic ketoacidosis in the
      emergency room.
AB  - BACKGROUND/AIMS: The aim of this study was to examine a plausible correlation
      between venous and arterial blood gas values in acidotic patients with chronic
      uremia or diabetic ketoacidosis (DKA). METHODS: A total of 152 arterial and 152
      venous blood samples from uremic patients (n = 100), DKA patients (n = 21) and
      healthy controls (n = 31) were analyzed for measurements of blood gas and acid
      base status. RESULTS: The means of arterial and venous pH, and arterial and
      venous HCO(-)(3) values for the uremic patients were 7. 17 +/- 0.14, 7.13 +/-
      0.14, 10.13 +/- 4.26 and 11.86 +/- 4.23 mmol/l, respectively. The respective mean
      differences between arterial and venous pH values and arterial and venous HCO(
      )(3) values were 0.04 +/- 0.02 and -1.72 +/- 0.42 mmol/l, respectively, for these
      patients. The means of the laboratory findings of DKA patients were arterial pH,
      7.15 +/- 0.15; venous pH, 7.10 +/- 0.15; arterial HCO(-)(3), 8. 57 +/- 5.71
      mmol/l and venous HCO(-)(3), 10.46 +/- 5.73 mmol/l. The respective mean
      differences between arterial and venous pH and arterial and venous HCO(-)(3) for
      this group were calculated to be 0. 05 +/- 0.01 and -1.88 +/- 0.41 mmol/l. In the
      healthy controls, the means of arterial and venous pH, and arterial and venous
      HCO(-)(3) values were 7.39 +/- 0.02, 7.34 +/- 0.02, 24.91 +/- 0.82 and 26.57 +/-
      0.83 mmol/l, respectively. For the healthy controls the mean differences between
      the respective values in arterial and venous pH, and arterial and venous HCO(
      )(3) were 0.05 +/- 0.01 and -1.66 +/- 0. 58 mmol/l. Although in healthy controls
      the correlation between arterial and venous pH values (r(2): 0.595) and arterial
      and venous HCO(-)(3) values (r(2): 0.552) were moderate, these correlations were
      significantly increased in both the acidotic patient group (r(2): 0.979 and
      0.990) and the DKA group (r(2): 0.989 and 0.995) CONCLUSION: A venous blood
      sample can be used to evaluate the acid-base status in uremic and DKA patients.

PMID- 10970987
TI  - Calciphylaxis in moderate renal insufficiency: changing disease concepts.
AB  - Calciphylaxis is a rare but frequently fatal complication in patients with end
      stage renal disease. Original concepts regarding groups at risk for the disease,
      predisposing factors, and associated morbidity have changed significantly in the
      past few years as more cases are reported. We present a patient who developed
      fatal calciphylaxis in the setting of moderate renal insufficiency to illustrate
      some of the evolving concepts in this disease process.

PMID- 10970988
TI  - Aspergillus peritonitis in continuous ambulatory peritoneal dialysis patients.
AB  - Aspergillus peritonitis is a rare and serious cause of peritonitis in continuous
      ambulatory peritoneal dialysis (CAPD) patients. We report 3 cases of aspergillus
      peritonitis in CAPD which were successfully treated by catheter removal and
      amphotericin. Two of the 3 patients returned temporarily to CAPD, but were
      subsequently transferred to hemodialysis because of membrane failure. A novel
      finding in 2 of the 3 cases was a positive Limulus amebocyte lysate test, despite
      negative bacterial cultures. We discuss the possible relevance of this finding to
      the diagnosis of aspergillus infections and emphasize the importance of early
      catheter removal for successful treatment of this condition.

PMID- 10970990
TI  - Acute renal failure from myoglobinuria secondary to myositis from severe
      falciparum malaria.
AB  - Renal disease is a common complication in malaria infection. In acute falciparum
      malaria renal involvement is usually mild, but in severe disease acute renal
      failure is a major problem. Acute renal failure has been attributed to ischaemic
      tubular necrosis from hypovolaemia resulting from vasodilatation due to
      endothelial injury. Though myositis is recorded as a common manifestation in
      falciparum malaria, only 1 case with myositis and myoglobinuria with acute renal
      failure has been documented; but no renal biopsy was performed in the patient. In
      the present study we examined the case of a 17-year-old man with severe
      falciparum malaria with myositis and myoglobinuria who developed acute renal
      failure requiring dialysis. Muscle biopsy revealed severe myositis with
      macrophages and T lymphocytes including CD4+ cells. The kidney biopsy showed
      scanty T cells and macrophages in the glomeruli which were only mildly
      hypercellular. The renal tubules showed myoglobin casts in the lumen and foci of
      interstitial inflammatory cells, including macrophages and T lymphocytes but no
      CD4+ cells. Rhabdomyolysis induced by macrophages and T cells with myoglobinuria
      and acute renal failure is a problem in severe falciparum malaria infection.

PMID- 10970989
TI  - Lactic acidosis in the setting of antiretroviral therapy for the acquired
      immunodeficiency syndrome. A case report and review of the literature.
AB  - Type B lactic acidosis, a rare but often fatal disorder, has been reported in 21
      AIDS patients on antiretroviral therapy (ART). We present an AIDS patient with
      severe and prolonged lactic acidosis on stavudine and lamivudine. The lactic
      acidosis occurred in the absence of mitochondrial myopathy, hepatomegaly, or
      liver failure. This is the second report of lactic acidosis in a patient on
      stavudine and lamivudine. This patient recovered after aggressive supportive
      therapy including intravenous alkali and fluid administration as well as
      continuous venovenous hemodiafiltration. A single dose of dichloroacetate (DCA)
      was associated with a decrease in the serum lactate level by 20%, which persisted
      for more than 24 h. Seventeen months after recovery, the patient was rechallenged
      with ART without recurrence of lactic acidosis. We review and summarize all
      reported cases of patients with ART-associated lactic acidosis reported in the
      English literature.

PMID- 10970991
TI  - Secondary polycythemia associated with idiopathic membranous nephropathy.
AB  - A 58-year-old male patient had secondary polycythemia associated with idiopathic
      nephrotic syndrome. The renal biopsy revealed membranous nephropathy, and the
      bone marrow biopsy disclosed hypercellular marrow with mild panhyperplasia. The
      concentration of serum erythropoietin was 8.5 mU/ml. The erythrocytosis was
      characterized by an increased red cell volume (40.2 ml/kg) and normal arterial
      oxygen saturation. There were no associated lesions that could induce secondary
      polycythemia, except the biopsy-proven membranous nephropathy. He was treated
      with prednisolone and cyclophosphamide, and the nephrotic syndrome was partially
      remitted after 6 weeks. With partial remission of nephrotic syndrome, the
      erythrocytosis was resolved. This case illustrates the rarely reported
      association of the nephrotic syndrome and erythrocytosis, and the resolution of
      erythrocytosis with improvement of nephrotic syndrome.

PMID- 10970992
TI  - Tumor necrosis factor, interleukin-6,and epinephrine are associated with
      hypermetabolism in AIDS patients with acute opportunistic infections.
AB  - During a 9-day period we investigated body composition, resting energy
      expenditure (REE), IL-6, TNF, and sTNFR-55 and sTNFR-75 plasma concentrations
      during infectious complications in 12 patients with HIV disease. At study entry,
      IL-6 was detectable in 5 and TNF in 10 patients. TNF was closely correlated with
      sTNFR-75 concentration (r = 0.84, p < 0.001) whereas sTNFR/sTNFR-55 ratio
      increased throughout the study. TNF concentrations were significantly correlated
      with the 24-hour excretion of epinephrine and norepinephrine (r = 0.64 and 0.69;
      each p < 0.01). Compared to expected values REE was increased by 34%. Body cell
      mass was the single best predictor of REE and explained 72% of its variance. In
      contrast, the deviation of measured from predicted REE was correlated with TNF
      and IL-6 concentrations (r = 0.9). We conclude that increased plasma
      concentrations of cytokines in complicated HIV disease display little biologic
      variability and relate to hypermetabolism in these patients.

PMID- 10970994
TI  - Substituting enzymatically interesterified butter for native butter has no effect
      on lipemia or lipoproteinemia in Man.
AB  - The aim of this study was to determine whether substituting enzymatically
      interesterified butter for native butter in the usual diet affects lipid and
      lipoprotein levels in man. Parameters studied were serum total cholesterol, LDL
      cholesterol, HDL-cholesterol, free cholesterol, phospholipids, triglycerides,
      apoA1 and apoB and the fatty acid composition of serum triglycerides, free fatty
      acids, phospholipids and cholesterol esters. Subjects were healthy volunteers and
      a controlled design was used. The only mathematically significant difference
      found when interesterified butter was substituted for butter was an about 7%
      lower fraction of oleic acid in the serum cholesterol esters (p = 0.005). In
      contrast to an earlier study where chemically interesterified butter fat was
      substituted for native butter, no indications are found in this study that
      replacing native butter by enzymatically interesterified butter, in amounts
      normally consumed, may have any beneficial effect on health.

PMID- 10970993
TI  - Dietary supplementation of a natural isomer mixture of beta-carotene inhibits
      oxidation of LDL derived from patients with diabetes mellitus.
AB  - BACKGROUND: Accelerated atherosclerosis is common in patients with diabetes
      mellitus which may be linked to increased lipid peroxidation. Therefore, we
      compared the oxidation of LDL derived from patients with diabetes to
      normoglycemic controls and followed-up the effect of dietary beta-carotene
      supplementation on LDL oxidation. METHODS: Twenty patients with long-standing non
      insulin-dependent diabetes mellitus were studied in comparison with age- and sex
      matched control subjects. Dunaliella bardawil-derived beta-carotene was
      supplemented to the patients for 3 weeks, 60 mg daily dose. LDL oxidation was
      analyzed by measuring malondialdehyde (MDA), lipid peroxides (PD), and conjugated
      dienes (CD) generation in response to CuSO(4)-induced oxidation. LDL lipid
      composition and the LDL associated vitamins A, E and carotenoids were also
      measured. RESULTS: LDL susceptibility to oxidation by CuSO(4) was increased in
      the patients by 40% with a 35% shorter lag time required for the initiation of
      LDL oxidation, i.e. 56 +/- 6 min in patients vs. 85 +/- 9 min in controls (p
      <0.01). Patients showed increased cholesterol/phospholipid and
      polyunsaturated/saturated ratios, as well as reduced content of LDL associated
      vitamins. Upon beta-carotene supplementation, there was a significant elevation
      in plasma and in LDL all-trans beta-carotene [from 0.296 +/- 0.020 to 0. 968 +/-
      0.133 microg/mg LDL protein (p < 0.01)] paralleled by a significant reduction in
      LDL susceptibility to oxidation, as exhibited by increased lag time up to 115 +/-
      10 min (p < 0.01) and reduction in MDA and PD generation (by 25 and 40%),
      respectively (p < 0.01). CONCLUSIONS: Increased susceptibility to oxidation of
      LDL derived from patients with diabetes mellitus is associated with abnormal LDL
      lipid composition and antioxidant content. Natural beta-carotene dietary
      supplementation normalizes the enhanced LDL oxidation and consequently may be of
      importance in delaying accelerated development of atherosclerosis in these
      patients.

PMID- 10970995
TI  - Concentrations of trace elements in extensively hydrolysed infant formulae and
      their estimated daily intakes.
AB  - The 18 trace elements Ba, Be, Bi, Cd, Co, Cs, Cu, La, Li, Mn, Mo, Pb, Rb, Sb, Sn,
      Sr, Tl, and Zn were determined in three extensively hydrolysed formulae by
      inductively coupled plasma mass spectrometry. Two formulae were whey
      hydrolysates, whereas one was based on soy-bovine collagen hydrolysate. Two skim
      milk powder reference materials, analyzed to ensure the analytical precision and
      accuracy of the applied procedure, showed good agreement with the certified
      values. Most of the elemental concentrations in this three formulae were
      comparable to each other. However, concentrations of Cs in one formula were
      approximately 20 times higher than in the other two formulae. Another formulae
      had much higher concentrations of La and Mn compared to the other two formulae.
      As regards Rb, all three formulae had distinctly lower concentrations than the
      four pre- and nine follow-up formulae investigated in a previous study. For the
      essential trace element Sn, much higher concentrations were found in the three
      extensively hydrolysed formulae ( approximately 8 microg/kg) when compared to pre
      and follow-up formulae (most of them <0.44 microg/kg). The concentrations of the
      toxic trace elements Cd, Pb, Sb, and Tl in extensively hydrolysed formulae did
      not exceed the concentrations in cow-milk-based formulae. Daily intakes provided
      by the investigated formulae differ by a factor of 1.6 for Co, of 3.2 for Cu, of
      8.7 for Mn, of 4.8 for Mo, and of 1.5 for Zn. Adequate daily intakes for Cu, Mo,
      and Zn are guaranteed by the use of most formulae, whereas only one hydrolysed
      formula fulfilled these requirements for manganese. Two hydrolysed formulae
      provide only approximately 50% of the recommended intakes for Mo.

PMID- 10970996
TI  - L-Carnitine, a 'Vitamin-like Substance' for functional food. Proceedings Of the
      symposium on L-carnitine, april 28 to may 1, 2000, zermatt, switzerland

PMID- 10970997
TI  - Postnatal changes in plasma ceruloplasmin and transferrin antioxidant activities
      in preterm babies.
AB  - Postnatal changes in plasma ceruloplasmin ferroxidase and transferrin iron
      binding antioxidant activity were studied in 10 healthy preterm babies during the
      first 6 weeks of life. Ceruloplasmin levels and ceruloplasmin ferroxidase
      activity were low at birth, remained stable for the first 3 weeks, and increased
      between 3 and 6 weeks. The transferrin levels were also low at birth, and this
      finding persisted throughout the 6-week study period. However, although the
      plasma iron-binding antioxidant activity was correspondingly low at birth, it
      thereafter rose and remained high. In four cord blood samples, but not in
      subsequent postnatal samples, peroxidation was actually stimulated in the assay
      measuring plasma iron-binding antioxidant activity. We have previously shown that
      this phenomenon is probably due to the presence of non-protein-bound iron.

PMID- 10970998
TI  - Maturational changes of lymphocyte surface antigens in human blood: comparison
      between fetuses, neonates and adults.
AB  - The objective of this study was to investigate the maturational changes of
      lymphocyte surface antigens during ontogeny from fetuses to adults using the
      proven whole blood lysis technique. Two-color flow cytometric analysis of
      lymphocyte surface markers was performed on 20 fetal blood samples obtained by
      cordocentesis, 70 cord blood and 30 adult blood samples. The leukocyte count and
      all T-cell subsets were highest in neonates compared to fetuses and declined into
      adulthood. In contrast, the percentage of CD2+ T cells (fetal blood 57% versus
      adult blood 82%; p </= 0.001), CD3+ T cells (fetal blood 52% versus adult blood
      77%; p </= 0.001), CD4+ T cells (fetal blood 39% versus adult blood 50%; p </=
      0.05) and CD8+ T cells (fetal blood 15% versus adult blood 24%; p </= 0.001)
      showed a significant increase from fetuses to adults. The absolute and relative
      amounts of B cells were highest in fetuses (fetal blood 547 x 10(6)/l, 18%)
      followed by a steady decline to adulthood (adult blood 243 x 10(6)/l, 13%; p </=
      0.001). The discordance between the absolute and relative size of lymphocyte
      subpopulations emphasizes the consideration of both variables in the assessment
      of lymphocyte maturation. The presented data may contribute to a better knowledge
      of the maturation of the immune system.

PMID- 10970999
TI  - Placental transfer of pyrimethamine studied in an ex vivo placental perfusion
      model.
AB  - Pyrimethamine is used as and anti-infectious agent because of its antifolate
      properties. Its action is synergistic with that of dapsone and sulfamides on
      Toxoplasma gondii. The goal of the present study was to evaluate the placental
      transfer of pyrimethamine in an ex vivo model of perfused human placental
      cotyledon at term. Human placentas were perfused according to the slightly
      modified method of Schneider. The pyrimethamine fetal transfer rate was
      approximately 30%, while cotyledon clearance was about 1.8 ml/min. The placental
      transfer of pyrimethamine seems to be independent of the maternal concentrations
      of pyrimethamine, suggesting passive diffusion mechanisms or a nonsaturable
      active transport at the tested concentrations.

PMID- 10971000
TI  - A comparison of arginine vasopressin levels and fluid balance in the perinatal
      period in infants who did and did not develop chronic oxygen dependency.
AB  - Arginine vasopressin (AVP) levels on days 1, 3 and 5 and fluid balance in the
      perinatal period were assessed in 60 infants, median gestational age 27 weeks
      (range 24-33). Fluid input and output, urine osmolality and episodes of
      hyponatraemia were recorded on a daily basis. Forty-one infants subsequently
      developed chronic lung disease (CLD), they were more immature, of lower
      birthweight and had higher AVP levels on days 3 and 5 (p < 0.05) than the rest of
      the cohort. Despite similar levels of fluid input, compared to the non-CLD
      infants, those who developed CLD had higher urine osmolalities on days 1, 5, 6
      and 7 (p < 0.05), but there were not significant differences between the two
      groups regarding urine output or episodes of hyponatraemia. Logistic regression
      analysis revealed AVP levels on day 3 were significantly correlated with the
      duration of oxygen dependency independent of other factors. We conclude elevated
      AVP levels in the perinatal period are associated with CLD development, but our
      results suggest they have little functional significance.

PMID- 10971001
TI  - Urinary nitric oxide in newborns with infections.
AB  - BACKGROUND: Neonatal sepsis is a major problem in newborn nurseries because of
      the difficulty in early diagnosis and because of the high morbidity and
      mortality. The objective of the present study was to investigate whether urinary
      nitric oxide (NO) levels could be useful for the diagnosis of infected newborns.
      METHODS: Newborns with suspected infection according to previously defined
      criteria between ages of 1-7 days and 8-30 days were included as the study groups
      (p) to be compared with age-matched healthy controls (c). Urine NO levels were
      assayed by Sievers NOA based on chemiluminescence and expressed as corrected for
      urine creatinine. RESULTS: 20 newborns with suspected infection at 1-7 days of
      age (group 1p) were compared with 45 healthy age-matched newborns (group 1c). 16
      newborns with suspected infection at 8-30 days of age (group 2p) were compared
      with 15 healthy age-matched newborns (group 2c). The groups were similar with
      regard to birth weight and gestational age; however, the urinary NO levels in
      newborns with suspected infection at 1-7 days of age (80.25+/-60.68 micromol/mg
      creatinine) were higher than in healthy newborns (25.45+/- 19.35 micromol/mg
      creatinine). Similarly, newborns with suspected infection at 8-30 days of age had
      higher urinary NO levels (81.78+/- 40.43 micromol/mg creatinine) than age-matched
      controls (36.99+/-24.58 micromol/mg creatinine; p < 0.05). The sensitivity of
      urinary NO levels to detect infection was 50% in both age groups, and the
      specificity was 95% for 1-7 days of age and 93% for 8-30 days of age. Groups 1p
      and 2p were similar with regard to NO production. Altogether 12 patients had
      culture-proven sepsis, 11 patients had clinical sepsis, and 13 patients had other
      infections. The NO levels were similar in patients with culture-proven and
      clinical sepsis and higher than in patients with other infections. No difference
      was observed among NO levels of patients with gram-positive and gram-negative
      sepsis. CONCLUSIONS: Urinary NO levels which are quick and easy to measure are
      higher in infected newborns as compared with controls, and although the
      specificity is good, the sensitivity of the test is low, necessitating the use of
      another marker in addition to NO.

PMID- 10971002
TI  - Influence of inhibition of nitric oxide synthesis on cardiac function in the
      newborn lamb after hypoxic-ischemic injury.
AB  - The aim of the present study was to investigate the effect of immediate post
      hypoxic-ischemic (HI) inhibition of nitric oxide synthesis by N(omega)-nitro-L
      arginine (NLA) on cardiac function and reactive oxygen species production.
      Fifteen newborn lambs were subjected to severe HI. Upon resuscitation 5 received
      10 mg NLA/kg, 4 40 mg NLA/kg and 6 a placebo. Left ventricular (LV)
      contractility, cardiac output (CO), non-protein-bound iron (NPBI), ratio of
      reduced/oxidized ascorbic acid, alpha-tocopherol, sulfhydryl groups and
      malondialdehyde were measured before and 15, 60 and 120 min after resuscitation.
      There was a significant decrease in CO in all 3 groups at 60 min post-HI (p <
      0.05). Reactive oxygen species production was also highest at 60 min post-HI
      (significantly increased NPBI and decrease in sulfhydryl groups in control lambs;
      p < 0.05). These results suggest neither a positive nor a negative effect of
      nitric oxide synthesis inhibition on post-HI myocardial performance but may
      suggest a positive effect of NLA on reactive oxygen species-mediated post-HI
      damage.

PMID- 10971003
TI  - Secretion of insulin-like growth factor-II into bile of rats of different ages.
AB  - Bile from rats of different ages (suckling 10-12 days; weanling 30-33 days, and
      adult 60-70 days) was collected and studied for the presence of immuno- and
      receptor-assayable insulin-like growth factor-II (IGF-II) concentrations.
      Concentrations of RIA IGF-II in bile were highest in suckling rats (230 +/- 38
      ng/ml) and lowest in adults (47 +/- 7 ng/ml). These concentrations were
      approximately twice those of the bile IGF-I concentration in sucklings, as
      measured in a previous study. Selected bile samples were also assayed using a
      competitive binding assay with a crude preparation of adult rat liver membranes
      bearing the IGF-II receptor. These studies confirmed the presence of receptor-
      (as well as immuno-) active IGF-II in bile. Since bile flow rates increased
      dramatically after the suckling period, bile delivery rates of IGF-II were
      normalized as picograms per gram body weight per hour. When such calculations
      were done, bile IGF-II delivery rates to the small intestine were highest in
      sucklings and weanlings in comparison to adult rats. Thus non-enterically derived
      (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be
      approximated at roughly 1 microg/day. Unlike IGF-I, intravenously injected IGF-II
      could not be detected in suckling bile, suggesting a predominantly hepatic
      origin. From this study we conclude that there exists a significant delivery of
      receptor-active IGF-II to the gastrointestinal tract of rats of all ages.

PMID- 10971004
TI  - Effects of correction of hypocalcemia on cardiac function in the newborn lamb.
AB  - The effect of correction of hypocalcemia on cardiac function in the neonate is
      unclear. Therefore, we evaluated changes in hemodynamic variables and cardiac
      contractility in a hypocalcemic neonatal lamb model. Baseline serum ionized
      hypocalcemia was induced via chelation with intravenous EGTA. Cardiac
      contractility, measured as end-systolic elastance, did not change with correction
      of hypocalcemia in this model. In contrast, the variable dP/dt(max), a load
      dependent index of contractility, showed an increase with calcium administration
      while the end-diastolic volume decreased, suggesting that diastolic function or
      early systolic function had changed. Systemic vascular resistance, cardiac
      output, and heart rate did not change significantly with correction of
      hypocalcemia. The results of this study suggest that in our newborn lamb model,
      cardiac contractility is insensitive to ionized calcium and may reflect cardiac
      immaturity, but that there may be an effect of calcium administration on
      diastolic or early systolic function.

PMID- 10971005
TI  - Effects of anti-CD18 monoclonal antibody, R15.7, on the cardiopulmonary
      manifestations of group B streptococcal sepsis in piglets.
AB  - We hypothesized that anti-CD18 monoclonal antibody, R15.7, a murine IgG(1)
      antibody which blocks leukocyte-endothelial cell adherence, might ameliorate the
      cardiopulmonary manifestations of sepsis secondary to group B streptococci (GBS).
      Twenty-six anesthetized, mechanically ventilated newborn piglets received a
      continuous infusion of GBS (7.5 x 10(9) cfu/kg/min) and were randomly assigned to
      a treatment group receiving R15.7 (1 mg/kg i.v.) 15 min prior to GBS infusion or
      to a control group. Cardiopulmonary measurements, arterial blood gases and
      peripheral blood leukocytes were obtained over 120 min of R15.7 infusion. GBS
      infusion caused significant increases in pulmonary artery and systemic arterial
      blood (Psa) pressures, pulmonary vascular (PVR) and systemic vascular (SVR)
      resistances, and PVR/SVR ratio with decreases in cardiac output and stroke
      volume. R15.7-treated piglets maintained significantly higher Psa (p < 0.003),
      dynamic lung compliance (p < 0.04), PaO2 and pH (p < 0.05), and lower total lung
      resistance (p < 0.01) and PaCO2 (p < 0.04). A longer median survival time was
      observed in the treatment group (p < 0.01). These data suggest that
      administration of a CD18-blocking agent prolongs survival in a young animal model
      of GBS sepsis, possibly secondary to improved tissue perfusion, lung mechanics
      and acid-base status.

PMID- 10971006
TI  - Surfactant tracheobronchial lavage for the management of a rabbit model of
      meconium aspiration syndrome.
AB  - We evaluated the effect of tracheobronchial lavage with diluted surfactant
      solution (bovine lipid extract surfactant, bLES) in a rabbit model of meconium
      aspiration. All animals were anaesthetized, tracheotomized and given 3-4 ml/kg of
      25% slurry of human meconium into the endotracheal tube and mechanically
      ventilated for 1 h. The animals were then randomly assigned to surfactant lavage
      (n = 12) with 15 ml/kg of diluted surfactant at a concentration of 5.4 mg
      phospholipid/ml administered in aliquots of 2 ml; or simple endotracheal suction
      (control n = 12) when the oxygenation index (OI) was >/=15. Changes in the
      arterial blood gases and the histomorphological and radiological appearances of
      the lungs were recorded. The OI and arterial/alveolar oxygen tension (a/A PO2) of
      the surfactant lavage group improved significantly at 5 min post-treatment, and
      these improvements were observed throughout the ensuing 4 h of ventilation. There
      was significantly more solid content recovered by surfactant lavage compared with
      the control group (p = 0.0001). Radiologically, the post-treatment air space
      opacification scores of the lavage group were significantly lower compared with
      the control (p = 0.002). The post-treatment radiographs of the lavage-treated
      rabbits were rated by the radiologist, who was blinded to the treatment groups,
      as much improved in 5 and improved in 4, whereas the control rabbits were rated
      as much worse in 3 and worse in 4. Histological examination showed the lungs of
      the lavaged rabbits had significantly more normal airway (p < 0.0001), more
      fields showing completely normal airspace (p = 0.0001) and less fields showing
      severe overdistension with meconium (p = 0.0005). We concluded that lavage with
      diluted surfactant solution effectively washed out the meconium, improved gases
      exchanges, and improved the histological and radiological appearances in the
      rabbit model of MAS.

PMID- 10971007
TI  - Endotracheal measurement of thyroarytenoid activity in newborn lambs.
AB  - Laryngeal control of expiratory airflow is a principal means by which the newborn
      establishes and maintains absolute lung volume. Specifically, retardation of
      expiratory airflow is effected by the major adductors of the larynx, the
      thyroarytenoid (TA) muscles. The long-term aim of this research is to determine
      if monitoring TA activity can be used to optimize absolute lung volume during
      artificial ventilation of the human baby. This initial study, performed in
      unanesthetized chronically instrumented newborn lambs, tests the hypothesis that
      the timings of the onsets, peaks and durations of TA activity recorded by the
      endotracheal electrode are equivalent to those measured by a surgically placed
      intramuscular electrode. Endotracheal measurement of TA activity is accurate and
      specific and can monitor changes in airway pressure and lung volume.

PMID- 10971008
TI  - High prevalence of factor V Leiden mutation in mothers of premature neonates.
AB  - The prevalence of the Leiden mutation was tested in 50 mothers of premature
      infants and in 56 mothers of intrauterine-growth-retarded neonates. The
      prevalence of the Leiden mutation was 7.2% in the mothers of growth-retarded
      neonates and 18% in the group of mothers of premature infants, the latter being
      significantly higher than the 6.3% prevalence of this mutation in healthy
      Hungarian subjects (p < 0.01). In spite of the relatively small number of mothers
      examined, the unexpected finding may call attention to a hitherto unknown
      relationship.

PMID- 10971009
TI  - Revisiting the concept of identifiable neurons.
AB  - Although eutely in nematodes was known, giant neurons in several taxa and unique
      motor neurons to leg muscles in decapod crustaceans, the idea that many animals
      have many identifiable neurons with relatively consistent dynamical properties
      and connections was only slowly established in the late 1960s and early 1970s.
      This has to be one of the important quiet revolutions in neurobiology. It
      stimulated a vast acquisition of specific information and led to some euphoria in
      the degree and pace of understanding activity of nervous systems and consequent
      behavior in terms of neuronal connections and properties. Some implications,
      problems and opportunities for new discovery are developed. The distribution of
      identifiable neurons among taxa and parts of the nervous system is not yet
      satisfactorily known. Their evolution may have been a case of several independent
      inventions. The degree of consistency has been quantified only in a few examples
      and the plasticity is little known. Identified neurons imply identifiable
      circuits but whether this extends to discrete systems, functionally definable,
      seems likely to have several answers in different animals or sites. Very limited
      attempts have been made to extend the concept to cases of two or ten or a hundred
      fully equivalent neurons, on all kinds of criteria. These attempts suggest a much
      smaller redundancy and vaster number of types of neurons than hitherto believed.
      Theory as well as empirical information has not yet interpreted the range of
      systems from those with small sets of relatively reliable neurons to those with
      large numbers of parallel, partially redundant units. The now classical notion of
      local circuits has to be extended to take account of and find roles for the
      plethora of integrative variables, of evidence for neural processing independent
      of spikes and classical synapses, of spatial configurations of terminal arbors
      and dendritic geometry, of modulators and transmitters, degrees of rhythmicity
      (regularity varying several orders of magnitude), and of synchrony. Adequate
      language and models need to go beyond 'circuits' in any engineering sense.
      Identifiable neurons can contribute to a broad spectrum of issues in
      neurobiology.

PMID- 10971010
TI  - The interneurons of the abdominal positioning system of the crayfish. How these
      neurons were established and their use as identified cells and command elements.
AB  - Arthropods with segmented abdomens show similar abdominal positioning behaviors.
      It has been possible to gain some understanding of the neural basis of these
      behaviors in lobsters and crayfish using standard intracellular and dye-filling
      techniques. Typically crayfish and lobsters have six abdominal segments each
      controlled by a set of flexor and extensor tonic muscles. Each segment has a
      dozen tonic motor neurons controlled in turn by a large number of interneurons. A
      similar set of phasic muscles, motor neurons and interneurons control a fast
      system. The fast components underlie such behaviors as escape and swimming.
      Lucifier-filled microelectrodes were used to stimulate, record and dye-fill the
      motor neurons and interneurons of the tonic systems. It was soon apparent that
      all of these neurons are identifiable. These data allowed us to determine how
      many interneurons served in a circuit generating a behavior, while the use of
      pairs of electrodes permitted the study of synaptic interactions between
      interneurons. Interneurons involved in abdominal positioning produced either
      flexion (flexion producing interneurons or FPI), extension (EPI) or inhibition
      (I). Significantly, FPIs tended to synaptically excite other FPIs and inhibit
      EPIs. In turn EPIs excited other EPIs and inhibited FPIs. As a result, impaling
      and stimulating an FPI, for example, tended to recruit others and their combined
      activity evoked a natural-looking behavior. The inhibition between FPI and EPI
      and vice versa tended to account for the reciprocity seen between the two
      behaviors in all experiments. Finally the synaptic connections between EPI-EPI on
      FPI-FPI were found to be essentially invariable. Thus repeated stimulation of an
      FPI or the stimulation of this same FPI in another preparation, at another time,
      gave essentially the same overall behavior such that the stimulation of one FPI
      or EPI could evoke a wide spread output resembling a normal behavior.

PMID- 10971011
TI  - Network architectures and circuit function: testing alternative hypotheses in
      multifunctional networks.
AB  - Understanding how species-typical movement patterns are organized in the nervous
      system is a central question in neurobiology. The current explanations involve
      'alphabet' models in which an individual neuron may participate in the circuit
      for several behaviors but each behavior is specified by a specific neural
      circuit. However, not all of the well-studied model systems fit the 'alphabet'
      model. The 'equation' model provides an alternative possibility, whereby a system
      of parallel motor neurons, each with a unique (but overlapping) field of
      innervation, can account for the production of stereotyped behavior patterns by
      variable circuits. That is, it is possible for such patterns to arise as emergent
      properties of a generalized neural network in the absence of feedback, a simple
      version of a 'self-organizing' behavioral system. Comparison of systems of
      identified neurons suggest that the 'alphabet' model may account for most
      observations where CPGs act to organize motor patterns. Other well-known model
      systems, involving architectures corresponding to feed-forward neural networks
      with a hidden layer, may organize patterned behavior in a manner consistent with
      the 'equation' model. Such architectures are found in the Mauthner and
      reticulospinal circuits, 'escape' locomotion in cockroaches, CNS control of
      Aplysia gill, and may also be important in the coordination of sensory
      information and motor systems in insect mushroom bodies and the vertebrate
      hippocampus. The hidden layer of such networks may serve as an 'internal
      representation' of the behavioral state and/or body position of the animal,
      allowing the animal to fine-tune oriented, or particularly context-sensitive,
      movements to the prevalent conditions. Experiments designed to distinguish
      between the two models in cases where they make mutually exclusive predictions
      provide an opportunity to elucidate the neural mechanisms by which behavior is
      organized in vivo and in vitro.

PMID- 10971012
TI  - Attractors: architects of network organization?
AB  - An attractor is defined here informally as a state of activity toward which a
      system settles. The settling or relaxation process dissipates the effects
      produced by external perturbations. In neural systems the relaxation process
      occurs temporally in the responses of each neuron and spatially across the
      network such that the activity settles into a subset of the available
      connections. Within limits, the set of neurons toward which the coordinated
      neural firing settles can be different from one time to another, and a given set
      of neurons can generate different types of attractor activity, depending on how
      the input environment activates the network. Findings such as these indicate that
      though information resides in the details of neuroanatomic structure, the
      expression of this information is in the dynamics of attractors. As such,
      attractors are sources of information that can be used not only in adaptive
      behavior, but also to effect the neural architecture that generates the
      attractor. The discussion here focuses on the latter possibility. A conjecture is
      offered to show that the relaxation dynamic of an attractor may 'guide' activity
      dependent learning processes in such a way that synaptic strengths, firing
      thresholds, the physical connections between neurons, and the size of the network
      are automatically set in an optimal, interrelated fashion. This inter-relatedness
      among network parameters would not be expected from more classical, 'switchboard'
      approaches to neural integration. The ideas are discussed within the context of
      'pulse-propagated networks' or equivalently as 'spike-activated networks' in
      which the specific order in time intervals between action potentials carries
      important information for cooperative activity to emerge among neurons in a
      network. Though the proposed ideas are forward-looking, being based on
      preliminary work in biological and artificial networks, they are testable in
      biological neural networks reconstructed from identified neurons in cell culture
      and in simulation models of them.

PMID- 10971013
TI  - Preface: from basic uniformity to diversity in cortical organization.

PMID- 10971014
TI  - Taking the measure of diversity: comparative alternatives to the model-animal
      paradigm in cortical neuroscience.
AB  - Cortical neuroscience is founded on studies of a very few model organisms, mainly
      rats, cats, and macaque monkeys. The concentration of effort on such a few
      species would be defensible if cortical organization were basically uniform
      across mammals, as is commonly believed. Although there is little reason to doubt
      that some features of cortical organization are indeed widespread among mammals,
      phyletic variation in cortical organization is far more extensive than has
      generally been appreciated or acknowledged. Rats, for example, differ from other
      mammals in the genetics and chemistry of their cortical neurons, in connectivity
      and areal organization, and in the functions of specific cortical regions.
      Likewise, macaque monkeys, although widely used as models of the human visual
      system, lack a number of features found in human visual cortex. Given the
      variability of cortical organization, how should neuroscientists approach the
      study of nonhuman species, and what can we reasonably expect to learn from them?
      First, by examining a wider range of species than are currently employed, and by
      using modern techniques of phyletic analysis, neuroscientists can more rigorously
      identify those features of cortical organization that are, in fact, widely shared
      among mammals or among particular mammalian subgroups. Second, by taking account
      of variations, neuroscientists can abstract more reliable and general principles
      of structure-function relationships in the nervous system. Finally, freed from
      the doctrine of basic uniformity, neuroscientists can pursue the study of human
      cortical specializations, and so advance our understanding of what distinguishes
      humans as a biological species.

PMID- 10971015
TI  - Neurochemical and cellular specializations in the mammalian neocortex reflect
      phylogenetic relationships: evidence from primates, cetaceans, and artiodactyls.
AB  - Most of the available data on the cytoarchitecture of the cerebral cortex in
      mammals rely on Nissl, Golgi, and myelin stains and few studies have explored the
      differential morphologic and neurochemical phenotypes of neuronal populations. In
      addition, the majority of studies addressing the distribution and morphology of
      identified neuronal subtypes have been performed in common laboratory animals
      such as the rat, mouse, cat, and macaque monkey, as well as in postmortem
      analyses in humans. Several neuronal markers, such as neurotransmitters or
      structural proteins, display a restricted cellular distribution in the mammalian
      brain, and recently, certain cytoskeletal proteins and calcium-binding proteins
      have emerged as reliable markers for morphologically distinct subpopulations of
      neurons in a large number of mammalian species. In this article, we review the
      morphologic characteristics and distribution of three calcium-binding proteins,
      parvalbumin, calbindin, and calretinin, and of the neurofilament protein triplet,
      a component of the neuronal cytoskeleton, to provide an overview of the presence
      and cellular typology of these proteins in the neocortex of various mammalian
      taxa. Considering the remarkable diversity in gross morphological patterns and
      neuronal organization that occurred during the evolution of mammalian neocortex,
      the distribution of these neurochemical markers may help define taxon-specific
      patterns. In turn, such patterns can be used as reliable phylogenetic traits to
      assess the degree to which neurochemical specialization of neurons, as well as
      their regional and laminar distribution in the neocortex, represent derived or
      ancestral features, and differ in certain taxa from the laboratory species that
      are most commonly studied.

PMID- 10971016
TI  - Cortical organization in insectivora: the parallel evolution of the sensory
      periphery and the brain.
AB  - Insectivores are traditionally described as a primitive group that has not
      changed much in the course of mammalian evolution. In contrast, recent studies
      reveal a great diversity of sensorimotor specializations among insectivores
      adapted to a number of different ecological niches, indicating that there has
      been significant diversification and change in the course of their evolution.
      Here the organization of sensory cortex is compared in the African hedgehog
      (Atelerix albiventris), the masked shrew (Sorex cinereus), the eastern mole
      (Scalopus aquaticus), and the star-nosed mole (Condylura cristata). Each of these
      four closely related species lives in a unique ecological niche, exhibits a
      different repertoire of behaviors, and has a different configuration of
      peripheral sensory receptors. Corresponding specializations of cortical sensory
      areas reveal a number of ways in which the cortex has evolved in parallel with
      changes to the sensory periphery. These specializations include expansion of
      cortical representations (cortical magnification), the addition or loss of
      cortical areas in the processing network, and the subdivision of areas into
      modules (barrels and stripes).

PMID- 10971017
TI  - Arealization of the neocortex in mammals: genetic and epigenetic contributions to
      the phenotype.
AB  - The neocortex is composed of areas that are functionally, anatomically and
      histochemically distinct. In comparison to most other mammals, humans have an
      expanded neocortex, with a pronounced increase in the number of cortical areas.
      This expansion underlies many complex behaviors associated with human
      capabilities including perception, cognition, language and volitional motor
      responses. In the following review we consider data from comparative studies as
      well as from developmental studies to gain insight into the mechanisms involved
      in arealization, and discuss how these mechanisms may have been modified in
      different lineages over time to produce the remarkable degree of organizational
      variability observed in the neocortex of mammals. Because any phenotype is a
      result of the complex interactions between genotypic influences and environmental
      factors, we also consider environmental, or epigenetic, contributions to the
      organization of the neocortex.

PMID- 10971018
TI  - Neurogenesis and the evolution of cortical diversity: mode, tempo, and
      partitioning during development and persistence in adulthood.
AB  - The mammalian cerebral cortex varies enormously in absolute and relative size
      across species. These size differences reflect phyletic differences in the number
      and organization of cortical neurons, which in turn imply evolutionary changes in
      the developmental program that generates these neurons. Whereas patterns of
      symmetric and asymmetric modes of progenitor cell division during cortical
      neurogenesis are widely conserved among species, other proliferation parameters,
      including the timing and number of cell divisions, vary considerably. This
      variation contributes to the development of cortical size differences in mammals
      in general, and the expansion of neocortex in anthropoid primates (monkeys, apes,
      and humans) in particular. The disproportionate enlargement of anthropoid
      neocortex might also arise from regional 'border-shifting' within the embryonic
      telencephalon, causing expansion of the neurogenic region allocated for producing
      neocortex and concomitant diminution of neighboring olfactory regions.
      Neurogenesis also shows substantial phyletic differences in adult hippocampus, an
      archicortical structure. Therefore, variation in neurogenesis across species is
      not only a feature of early development, but is also a trait of adult cortical
      diversity.

PMID- 10971019
TI  - European Stroke Initiative recommendations for stroke management. European Stroke
      Council, European Neurological Society and European Federation of Neurological
      Societies.
AB  - This article summarises recommendations for acute management of stroke by the
      European Stroke Initiative (EUSI), on behalf of the European Stroke Council
      (ESC), the European Neurological Society (ENS), and the European Federation of
      Neurological Societies (EFNS).

PMID- 10971020
TI  - Recent infection as a risk factor for intracerebral and subarachnoid hemorrhages.
AB  - Previous infection has been shown to be a risk factor for acute cerebral
      ischemia. We tested the hypothesis that recent infection is also a risk factor
      for intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). We
      performed a case-control study with 56 consecutive patients with ICH, 44
      consecutive patients with SAH, and 56 and 44 neurological control patients,
      respectively. Infection within 4 weeks was associated with SAH independently of
      hypertension and smoking (p = 0.049). There was no significant association
      between infection and ICH. Recent infection, primarily upper respiratory tract
      infection, may be a risk factor for SAH by contributing to the formation and
      rupture of aneurysms.

PMID- 10971021
TI  - The thrombomodulin gene mutation G(127)-->A (Ala25Thr) and cerebrovascular
      disease.
AB  - BACKGROUND AND PURPOSE: Thrombomodulin is an integral part of the protein C
      anticoagulation pathway, and polymorphisms of its gene have been implicated in
      thrombosis. The point mutation G(127)-->A has recently been found to be
      associated with myocardial infarction. METHODS: We investigated this mutation in
      465 patients with acute stroke and 353 control subjects. Genomic DNA containing
      the region of interest was amplified by PCR, and differing genotypes were
      identified by RFLP. RESULTS: The A allele frequency was not statistically
      significantly different in the two groups, being 0.5% in the stroke group and
      0.7% in the control group. CONCLUSIONS: The point mutation G(127)-->A is an
      uncommon finding and, in this population, is unlikely to be a major risk factor
      for cerebrovascular disease.

PMID- 10971023
TI  - Epileptic seizures attributed to cerebral hyperperfusion after percutaneous
      transluminal angioplasty and stenting of the internal carotid artery.
AB  - Cerebral hyperperfusion syndrome as a complication of carotid endarterectomy
      (CEA) has been widely reported in the surgical literature. It may occur within
      hours to 3 weeks after CEA and is characterized by symptoms ranging from
      headaches, fits, confusion, focal neurological signs to intracerebral hemorrhage.
      Although percutaneous transluminal angioplasty (PTA) and stenting are
      increasingly performed as an alternative to CEA in the treatment of carotid
      artery stenosis, few cases of cerebral hyperperfusion injury following carotid
      stenting have been reported. We describe 2 cases of cerebral hyperperfusion
      syndrome following PTA and stenting for high-grade internal carotid artery (ICA)
      stenosis. Both cases involved a lesion of 95% in severity. The first case was a
      73-year-old man who developed generalized convulsion 7 h following stenting to
      the left ICA. The second case was an 80-year-old woman who developed recurrent
      right periorbital headache and confusion 16 h after stenting to the right ICA,
      followed by left upper limb seizure 14 days later. Both patients fully recovered
      without any intracerebral hemorrhage or infarction. To our knowledge, this is the
      first report of cerebral hyperperfusion injury after carotid stenting without
      associated intracranial hemorrhage and with full recovery. In the patient with
      neurological symptoms following carotid stenting, it is important to consider
      cerebral hyperperfusion syndrome as a differential diagnosis to embolic or
      hemorrhagic stroke since early recognition and meticulous control of blood
      pressure may prevent progression to cerebral hemorrhage and death.

PMID- 10971022
TI  - Early (99m)Tc-ethylcysteinate dimer brain SPECT patterns in the acute phase of
      stroke as predictors of neurological recovery.
AB  - OBJECTIVES: Accurate prediction of outcome in acute stroke would help in
      identifying subgroups of patients for therapeutic trials and intravenous
      thrombolysis. The purpose of this study was to prospectively test the hypothesis
      that brain SPECT, with (99m)Tc-L, L-ethylcysteinate dimer (ECD), a tracer
      sensitive to cell function, performed in the first hours after stroke onset, adds
      predictive power to concomitant neurological evaluation. METHODS: Twenty-four
      patients with a first-ever middle cerebral artery stroke were prospectively
      studied with ECD-SPECT within 12 h after stroke onset. Neurological evaluation
      was performed using Orgogozo's scale at admission and 3 months later in order to
      calculate the percent Martinez-Vila evolution indices (EI%). Semiquantitative
      visual analysis of SPECT images was performed in 6 cortical regions relevant for
      carotid artery territory. Both the extent and the intensity of cortical reduced
      ECD uptake were calculated, leading to an 'ischemia' score, corresponding to the
      sum of regions of interest (ROI) where ECD uptake was between 40 and 80% of the
      contralateral healthy hemisphere, and an 'irreversibly damaged tissue' (IDT)
      score, corresponding to an uptake below 40%, and a total score (ischemia + IDT).
      Each patient was assigned to one of three patterns: (1) pattern I with severe ECD
      cortical uptake reduction defined by at least one ROI with uptake under 40%, (2)
      pattern II with moderate ECD cortical uptake reduction (40-80%) only and (3)
      pattern III with normal ECD uptake. RESULTS: There were 11 patients (46%) with
      pattern I ECD-SPECT. This group had almost invariably (10/11 patients) a poor
      outcome. The 12 patients (50%) classified in pattern II had a variable clinical
      outcome, ranging from improvement to deterioration. The single patient with a
      normal SPECT (pattern III) had a full clinical recovery. Both total score and IDT
      score were strongly significantly correlated with neurological recovery EI%
      (respectively p = 0.006 and 0.004). Their predictive value was significantly
      higher than, and independent of, day 0 neurological evaluation. No patient had an
      increased ECD uptake. CONCLUSION: Our results show that the degree of ECD
      cortical uptake reduction, measured on early brain SPECT, is a strong predictor
      of neurological recovery. ECD-SPECT data have a higher predictive value than day
      0 neurological evaluation. The apparently better predictive value of ECD over
      hexamethylpropyleneamine oxime may reflect this tracer's brain retention
      mechanisms which are weighted more towards cell function than towards perfusion.
      ECD-SPECT is easily obtainable and may help in selecting out from therapy those
      patients who are likely to have either very good or very poor spontaneous
      outcome, and thus improve the assessment of acute stroke and the choice of
      therapeutic strategy.

PMID- 10971024
TI  - Swallowing disorders following acute stroke: prevalence and diagnostic accuracy.
AB  - We prospectively examined 128 patients with acute first-ever stroke to determine
      the prevalence of swallowing disorders, the diagnostic accuracy of our clinical
      assessment of swallowing function compared with videofluoroscopy, and
      interobserver agreement for the clinical and videofluoroscopic diagnosis of
      swallowing disorders and aspiration. We found clinical and videofluoroscopic
      evidence of a swallowing disorder in 51% [95% confidence interval (CI) 42-60%]
      and 64% (95% CI 55-72%) of patients, respectively, and aspiration in 49% (95% CI
      40-58%) and 22% (95% CI 15-29%) of patients, respectively. The optimal clinical
      criteria for detecting videofluoroscopic evidence of a swallowing disorder and
      aspiration were any clinical evidence of a swallowing disorder (sensitivity 73%,
      95% CI 62-82%; specificity 89%, 95% CI 76-96%), and any clinical evidence of
      aspiration (sensitivity 93%, 95% CI 76-99%; specificity 63%, 95% CI 53-72%). The
      interobserver agreement between two speech pathologists for the clinical
      diagnosis of a swallowing disorder (kappa: 0.82 +/- 0.09) and aspiration (kappa:
      0.75 +/- 0.09) was good, and between a speech pathologist and radiologist for the
      videofluoroscopic diagnosis of a swallowing disorder (kappa: 0.75 +/- 0.09) and
      aspiration (kappa: 0.41 +/- 0.09), it was good and fair, respectively. Although
      clinical bedside examination underestimates the frequency of swallowing
      abnormalities and overestimates the frequency of aspiration compared with
      videofluoroscopy, it may still offer valuable information for the diagnosis of
      swallowing impairment. Long-term follow-up studies are required to determine the
      independent functional significance of the findings of the bedside and
      videofluoroscopic examinations in predicting the occurrence of important outcome
      events such as aspiration pneumonia.

PMID- 10971025
TI  - Risk factors for lacunar infarcts.
AB  - Lacunar infarcts represent a stroke subgroup with controversial risk factors.
      Lacunar syndromes may be divided into two groups: the classic group (pure motor
      hemiplegia, pure sensory stroke, ataxic hemiparesis, dysarthria-clumsy hand
      syndrome, sensorimotor stroke) and the miscellaneous group including all other
      lacunar syndromes. We studied risk factors of 200 consecutive patients with
      symptomatic lacunar infarcts diagnosed by magnetic resonance imaging. This study
      tested whether lacunar infarcts represent a homogeneous subgroup of strokes or
      not. Using descriptive and bivariate statistics, we found that the prevalences of
      arterial hypertension and cigarette smoking are lower in the miscellaneous group.
      Analysis of variance shows a significant difference in age between subgroups
      without interaction of sex. Nevertheless, using multivariate analysis, we did not
      find a difference between subgroups. Thus, lacunar infarcts seem to be a
      homogeneous subgroup of strokes, and the miscellaneous group of lacunar infarcts
      may be included into the lacunar infarct group and not into the vertebrobasilar
      large-artery infarct group.

PMID- 10971026
TI  - Delayed intrahemispheric remote hypometabolism. Correlations with early recovery
      after stroke.
AB  - Although 'intrahemispheric diaschisis' (i.e. a hypometabolism affecting the
      cerebral hemisphere ipsilateral to but remote from the infarct) may classically
      exacerbate acute-stage neurological deficit and influence early recovery, it has
      been studied only rarely. Out of a series of 30 patients with first-ever middle
      cerebral artery (MCA) territory stroke, we analyzed the data from 19 survivors
      investigated by (15)O positron emission tomography (PET) both in the acute
      (within 5-18 h of clinical onset) and subacute (approximately 3 weeks later)
      stage, and for whom chronic-stage CT coregistered with PET was available to
      assess infarct topography and size. Orgogozo's MCA scale was used to assess
      neurological deficits at the time of, and recovery between, the PET studies.
      Oxygen consumption was obtained for both PET sessions for the whole ipsilateral
      hemisphere (excluding ventricles and infarct), as well as for the thalamus and
      the occipital and mesial-prefrontal cortex (i.e. potentially deafferented tissue
      outside the MCA territory). In all regions except the occipital cortex, the
      oxygen consumption significantly decreased between the first and the second
      session, without significant correlation with the concomitant changes in MCA
      scores. However, acute-stage mesial-prefrontal metabolism was significantly
      correlated with neurological recovery. Also, both the hemisphere and the mesial
      prefrontal metabolism at the second session were significantly correlated with
      both infarct size and concomitant MCA scores, but the latter relationship became
      insignificant when infarct size was taken into account. This study reveals no
      evidence of acute intrahemispheric diaschisis after MCA territory stroke in man.
      However, it documents for the first time a phenomenon of delayed intrahemispheric
      remote hypometabolism developing while the patients clinically recover. Because
      the degree of this secondary phenomenon is a function of infarct size, a
      mechanism of degeneration of the damaged neuron terminals is likely. Finally,
      contrary to other reports, neurological recovery was not a function of thalamic
      hypometabolism, but appeared to be influenced by acute-stage mesial-frontal
      metabolism, perhaps because this region is part of a network that has an
      important compensatory role in motor recovery.

PMID- 10971027
TI  - Cerebral microembolus detection in an unselected acute ischemic stroke
      population.
AB  - OBJECTIVE: The aims of this study were firstly to determine prevalence,
      frequency, and clinical significance of cerebral microemboli in an unselected
      acute ischemic stroke population and secondly to examine how this information may
      improve ischemic stroke subtype classification. METHODS: We intended to perform
      transcranial Doppler (TCD) microembolus monitorings of the middle cerebral artery
      (MCA) in the symptomatic hemisphere for 45 min in 120 consecutive patients with
      internal carotid artery territory ischemia. The first examination was performed
      within 72 h from start of symptoms and the second 5 +/- 1 days later. Platelet
      and coagulation system activation were measured following TCD monitoring in 38
      patients. The strokes were subtyped using the TOAST classification criteria, and
      the patients' clinical status was assessed at discharge using the Scandinavian
      Stroke Scale and the Barthel Index. RESULTS: Microembolus monitoring was
      technically possible in 83 (69.2%) of the 120 patients. Thirty-two (26.6%)
      patients had an inadequate temporal bone acoustic window or were too restless to
      allow long-time monitoring. In 5 (4.2%) patients the relevant MCA was occluded.
      Twenty-two (26.5%) of the 83 patients had microemboli despite the fact that over
      90% were receiving an antiplatelet or an anticoagulant treatment. The mean
      frequency of microemboli was 6.7 +/- 13.6 per 45 min. Microemboli were more
      prevalent in assumed cardioembolic stroke than in other subtypes of ischemic
      stroke (p = 0.047). We found no association between the presence of cerebral
      microemboli and the clinical outcome or the parameters for platelet or
      coagulation system activation. The presence of microemboli was not associated
      with in-hospital deaths (p = 0.17), whereas MCA occlusion was (p = 0.01).
      CONCLUSIONS: Cerebral microemboli are frequent in unselected acute ischemic
      stroke patients despite antiplatelet or anticoagulant treatment. TCD detection of
      microemboli provides valuable pathophysiological information and may, therefore,
      improve current ischemic stroke subtype classification.

PMID- 10971028
TI  - Chronological changes in cerebral air embolism that occurred during continuous
      drainage of infected lung bullae.
AB  - We present a 43-year-old man with cerebral air embolism that occurred during
      continuous drainage of infected lung bullae. This complication is extremely rare,
      and may have been caused by the passage of air into the pulmonary venous
      circulation through a bronchovenous fistula and/or damaged pulmonary vessels. Air
      densities were demonstrated along the right frontal gyri on a CT performed 1 h
      after the onset of embolism, then moved to the deep cortex after 2.5 h. Three
      days later, a cortical infarct accompanied with extensive white matter edema in
      the right frontal lobe was confirmed by MRI. These CT and MRI findings may
      indicate the passage of intravascular air from the superficial to the deep cortex
      and subsequent cerebral infarction.

PMID- 10971029
TI  - Stroke as the first manifestation of calcific aortic stenosis.
AB  - Heart valve calcifications are rarely recognized as a potential source for
      cerebral embolism. Previous studies have identified mitral, but not aortic, valve
      calcifications to be risk factors for stroke. Based on these studies, heart
      surgery is unlikely to be indicated in patients who present with a stroke and an
      'incidental' aortic valve calcification. We report a case of a 46-year-old man
      presenting with acute onset of left-sided weakness and numbness. A previous
      smoking history was the only cardiovascular risk factor found. Head CT scan
      revealed a right middle cerebral artery territory infarct and an adjacent high
      density lesion. CT angiography demonstrated the presence of calcific embolic
      material in the middle cerebral artery. A search for embolic sources revealed a
      calcific aortic stenosis (CAS). Initially placed on coumadin, the patient
      developed silent myocardial infarction 2 months later, presumed to be also
      embolic in origin from the CAS. After aortic valve replacement, the patient has
      been symptom-free during a 2-year follow-up. In conclusion, CT angiography may be
      the method of choice for detecting calcific cerebral emboli, and demonstration of
      a causal relationship between CAS and an embolic stroke by CT angiography may be
      an important adjunct in surgical decision-making.

PMID- 10971030
TI  - A case of diffuse cerebral vasospasm--possibly ergotamine-associated?

PMID- 10971031
TI  - New approaches towards ex vivo and in vivo gene therapy.
AB  - A number of hurdles have to be overcome for efficient and specific gene therapy
      approaches. Here, we report on two different strategies that should lead to an
      improvement of current protocols. A strategy is presented to tag unique
      chromosomal integration sites by means of retroviral infection, which can be
      reused for exchange with the gene of interest by action of site-specific
      recombinases. Targeting exchange is achieved in one step with 100% efficiency by
      a stringent positive selection, which makes further screening superfluous. With
      this strategy a predictable gene expression is obtained for foreign genes
      integrated into a predefined chromatin structure. A second approach aims at the
      stabilization of mouse retroviruses towards human serum which is a prerequisite
      for in vivo gene therapy protocols. To stabilize murine leukemia virus-based
      retroviruses against human serum, complement regulatory proteins were fused to
      the retroviral ENV proteins. This resulted in infectious and human complement
      protected particles.

PMID- 10971032
TI  - Emerging therapies in hepatology: liver-directed gene transfer and hepatocyte
      transplantation.
AB  - Gene transfer and epithelial cell transplantation technologies play an important
      role in the development of new therapeutic concepts for liver diseases. Although
      liver organ transplantation has revolutionized the treatment of a wide spectrum
      of acute and chronic liver diseases, gene- and cell-based therapies are emerging
      at an astonishing pace, because they promise to be less invasive, less costly and
      at least as effective as currently established therapy protocols. Experimental
      gene therapy models have been developed for a wide spectrum of liver diseases,
      including hereditary liver disorders, malignant liver disease and viral
      hepatitis. Hepatocyte transplantation (HcTx) is being explored as treatment of
      severe chronic and acute liver failure as well as for hereditary liver diseases.
      Most of these procedures and techniques are still experimental or have been
      applied to a small number of patients only. Rigorous clinical evaluation will
      finally demonstrate the usefulness of each new procedure in the daily clinical
      care of patients with liver disease. In this review, we have attempted to provide
      an introduction and survey of the topics of gene therapy and HcTx with specific
      examples of laboratory and clinical achievements highlighting potential
      applications in liver diseases.

PMID- 10971033
TI  - Bioartificial skin.
AB  - The loss of skin has been one of the oldest, yet most frequent and costly
      problems in our health care system. To restore functional and esthetic integrity
      in patients with unstable or hypertrophic scars, in burn patients and after skin
      loss for hereditary, traumatic or oncological reasons, an armamentarium of
      reconstructive surgical procedures including autogenous, allogenous and
      xenogenous tissue transfer as well as implantation of alloplastic materials has
      been favored. For several decades there has been increasing interest focused on
      'tissue engineering' of dermal, epidermal and full thickness skin substitutes by
      both biological and synthetic matrices. At our institution (Hannover Medical
      School), a collagen/glycosaminoglycan dermal regeneration matrix has been used
      for immediate dermal coverage after escharectomy in burn injuries as well as for
      dermal replacement in chronically unstable scars. This article gives an overview
      on the current state of the art in bioartificial skin as well as our personal
      experience with the collagen/glycosaminoglycan matrix for dermal replacement in
      different clinical situations.

PMID- 10971035
TI  - Effect of mechanical load on articular cartilage collagen structure: a scanning
      electron-microscopic study.
AB  - Little is known about the morphological effect of a mechanical load upon
      articular cartilage. The objective of this study was to describe and quantify the
      deformation of the articular cartilage collagen structure of the tibial plateau
      under static loading. Whole intact rabbit knee joints were loaded in vitro by
      simulating a quadriceps force of 3x, 1x or 0.5x body weight (high, medium, low)
      over durations of 30 or 5 min (long, short). Specimens were cryopreserved while
      under load and prepared for morphological evaluation by field emission scanning
      electron microscopy. Under high force and long duration loading the collagen
      fibers exhibited high deformation with an increased thickness of the layer of
      collagen fibers oriented almost parallel to the surface and a cartilage thickness
      reduced to 54%. Collagen fiber deformation occurred mostly in the transitional
      and upper radial zone. The area of tibial indentation and the cartilage thickness
      reduction increased with magnitude and duration of load. The collagen matrix did
      show a bulging edge at the border of the meniscus and exhibited remarkable
      deformation under the meniscus.

PMID- 10971034
TI  - Bioartificial cartilage.
AB  - Cartilage is a highly differentiated tissue. Its three-dimensional composition of
      cells and matrix is able to resist intensive mechanical loads. The capacity of
      cartilage tissue for regeneration is limited. Chondrocytes are responsible for
      matrix production of cartilage tissue. Enzymatic isolation and expansion of
      chondrocytes with cell culture techniques has been improved in the last years.
      These cells can be cultured on different three-dimensional culture systems
      suitable for transplantation to repair localized cartilage defects. Two types of
      bioresorbable polymer fleece matrices (PLLA and a composite fleece of
      polydioxanone and polyglactin) and lyophilized dura as a biological carrier are
      tested. Phenotypic and morphological appearance of the cultured articular rabbit
      chondrocytes is preserved on all three types of transport media. Production of
      glycosaminoglycans has been shown by Alcian blue staining, production of collagen
      by azan staining. Chondroitin 4- and 6-sulfate are detected immunohistochemically
      in the created constructs. The different carriers have specific characteristics
      regarding their suitability for the creation of bioartificial cartilage. This
      tissue is transplantable into articular cartilage defects and could, therefore,
      improve the minor intrinsic healing capacity of cartilage tissue.

PMID- 10971037
TI  - Differentiation of myoblasts in serum-free media: effects of modified media are
      cell line-specific.
AB  - Myoblast cell lines are grown and differentiated readily in cell culture. Two
      cell lines typically used for investigating the growth and differentiation of
      muscle are the mouse cell line C2C12 and the rat cell line L6. The
      differentiation of these cells in vitro requires a switch from a serum-rich
      medium to a less rich medium after the cells have reached confluence. Since the
      components present in serum are not well characterized, the use of a better
      defined medium for these studies was investigated. C2C12 and L6 myoblasts were
      differentiated in both serum-containing and serum-free media. The differentiation
      state of these cultures was then tested both microscopically and biochemically.
      Cultures were checked for myotube formation, the activity of creatine
      phosphokinase and the presence of sarcomeric actin. In C2C12 cells, the extent of
      differentiation was greater in the serum-free than in the serum-containing
      system. In both media types, the C2C12 cells produced sarcomeric actin, showing
      the presence of sarcomere structure in the myotubes. In L6 cells, however,
      myotubes were readily formed in medium containing 2% horse serum, but not in the
      serum-free system. In addition, the ability of C2C12 cells to differentiate on
      substrates coated with extracellular matrix proteins was shown to be media
      dependent. The presence of extracellular matrix proteins did not enable L6 cells
      to form myotubes when cultured in serum-free media. Primary cultures of chick
      myoblasts were able to differentiate in both media tested, with Dulbecco's
      modified Eagle medium containing horse serum being a more efficient medium for
      cell fusion. This study shows a divergence in muscle cell line responses in three
      cell lines, two of which are typically used as 'model systems' for understanding
      muscle growth and development.

PMID- 10971036
TI  - Enhancement of toluidine blue staining by transforming growth factor-beta,
      insulin-like growth factor and growth hormone in the temporomandibular joint of
      aged mice.
AB  - Osteoarthritic lesions appear in the articular cartilage of the temporomandibular
      joint of mice aged 7 months and older. Reduced rate of proteoglycan (PG)
      synthesis leading to destruction of the articular cartilage was observed in this
      joint. The purpose of the present study was to test the ability of transforming
      growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1) and growth
      hormone (GH) to induce PG synthesis in joint cartilage of aged animals and to
      compare it with the effect of interleukin-1alpha (IL-1alpha). Mandibular condyle
      explants from 18-month-old mice were cultured up to 72 h in serum-free medium,
      supplemented with IL-1alpha (TGF-beta1 (0.1-5.0 ng/ml), TGF-beta1 (1.0 ng/ml) +
      IGF-1 (2 ng/ml) or GH (10 ng/ml). The incorporation of (35)S-SO(4) into sulfated
      PG was tested. Cartilage samples were processed for histomorphometry using
      sections stained with 0.1% toluidine blue (TB), pH 1.8. Results indicated that in
      cultures supplemented (48 h) with either TGF-beta, TGF-beta + IGF-1 or with GH,
      an increased height and area of TB-positive staining as well as increased
      incorporation of (35)S-SO(4) into sulfated PG were observed. In contrast, the
      cytokine IL-1alpha exerted an inhibitory effect on TB staining and on (35)S-SO(4)
      incorporation. The present study demonstrated that in vitro supplementation of IL
      1alpha to mandibular condyle cartilage reduced the height and area of TB staining
      and incorporation of (35)S-SO(4), whereas TGF-beta1, TGF-beta1 + IGF-1 or GH
      increased the height and area of TB staining and increased incorporation of (35)S
      SO(4). The two parameters used to identify increased PG synthesis were shown to
      reveal similar results and were useful for studying the dynamic events taking
      place in cartilage destruction and repair in osteoarthritis.

PMID- 10971038
TI  - Distinct myosin heavy chain isoform transitions in developing slow and fast cat
      hindlimb muscles.
AB  - The expression of myosin heavy chain (MHC) isoforms leading to adult fiber
      phenotypes in the tibialis anterior (TA) and soleus muscles of the cat were
      investigated from embryonic day 35 to 1 year after birth. Electrophoresis and
      immunoblotting of myofibrils demonstrated the expression of 5 different MHC
      isoforms, i.e. I, IIa, IIx, embryonic, and neonatal, during development. Based on
      electrophoresis, the adult-like MHC composition of the soleus and TA were not
      observed until postnatal day 40 (P40) and 120 (P120), respectively. In contrast,
      immunohistochemical analyses revealed that the adult-like fiber phenotype
      composition was attained much later (P120) in the soleus. The existence of
      multiple MHC isoforms in individual fibers suggested that transitions occurred
      until P120 in both muscles. Adult type I fibers were first observed at P1. Adult
      IIA fibers were first observed at P30 in the TA and P40 in the soleus. IIX fibers
      were not identified until P40 in the TA. The transition to the predominantly slow
      phenotype of the soleus involved a gradual loss of embryonic and fast isoforms
      accompanied by an accumulation of slow MHC. In contrast, the expression of slow
      and fast MHC in the fast TA muscle was relatively unchanged throughout
      development. These results show that the establishment of a given MHC-based fiber
      phenotype varies significantly between slow and fast muscles in the kitten.

PMID- 10971039
TI  - Capillarity, fibre types and fibre morphometry in different sampling sites across
      and along the tibialis anterior muscle of the rat.
AB  - Capillarity, fibre types, fibre cross-sectional areas and perimeters were studied
      along and across the rat tibialis anterior muscle. The muscle was sectioned at
      three different levels (proximal, equatorial and distal) choosing five sampling
      fields for measurements at each level (from anterior to posterior and lateral to
      medial zones). Significant differences were found in the percentage of fibre
      types and capillarity between different fields of the same muscle section. Slow
      oxidative fibres were confined to the posterior muscle zone with a maximum of
      3.7%. The posterior fields also had a greater percentage of fast oxidative
      glycolytic fibres at proximal (72.3%) and equatorial (61.3%) levels, but a lower
      value at the distal level (44.8%) and lower capillary density counts in total
      cross-section means (758 vs. 1,069 capillaries/mm(2) in equatorial and 1,035
      capillaries/mm(2) at proximal levels). The uneven distribution of both fast fibre
      types and the different degrees of capillarisation along the muscle are
      statistically significant and may be due to different biomechanical performances
      along the rat tibialis anterior. Fibre size was significantly larger at the
      distal level, but no morphometric differences were found across the section of
      the same level. At the distal level, the mean total fibre area of fast glycolytic
      fibres (5,130 microm(2)) and fast oxidative glycolytic fibres (2,493 microm(2))
      contrasted with values at the proximal (fast glycolytic: 4,070 microm(2), fast
      oxidative glycolytic: 1,970 microm(2)) and equatorial (fast glycolytic: 3,535
      microm(2), fast oxidative glycolytic: 1,714 microm(2)) levels. The differences
      along and across the muscle show the need to design a standardised procedure for
      sample location when performing comparative studies of morphofunctional adaptive
      changes in skeletal muscle. A significant difference between individuals
      (animals) in all parameters was evident and should be taken into consideration
      when analysing the variability: the factor 'animal' should be considered in
      multiway ANOVAs, especially when low sample sizes are used.

PMID- 10971040
TI  - Development of chick cardiomyocytes: modulation of intermediate filaments by
      basic fibroblast and platelet-derived growth factors.
AB  - Recent studies suggest that peptide growth factors play a functional role in
      cardiac muscle. To test whether embryonic cardiac muscle is a target for
      regulation by basic fibroblast growth factor and platelet-derived growth factor,
      we analyzed the effects of these peptides on the expression of the intermediate
      filaments desmin and vimentin at the subcellular level during development. Sodium
      dodecyl sulfate-gel electrophoresis, immunoblotting and fluorescence-activated
      cell sorting analysis were used to study the effect of basic fibroblast growth
      factor and platelet-derived growth factor on cultures of chick cardiomyocytes
      during development. Cytoplasmic and cytoskeletal concentrations of desmin and
      vimentin were dependent on the stage of embryonic development and on the type of
      growth factor added to the culture. The most significant finding was the increase
      in desmin expression in the cytoplasmic and cytoskeletal compartments after
      treatment with basic fibroblast growth factor (10 ng/ml) of chick heart cells at
      Hamburger and Hamilton stage 19. In more mature stages, basic fibroblast growth
      factor did not modify the levels of desmin expression. However, this factor led
      to a progressive deceleration in the rate of increase in vimentin expression.
      Platelet-derived growth factor increased vimentin expression in all stages
      studied, the greatest increases appearing in early stages of heart development.
      Our findings support the hypothesis that basic fibroblast growth factor plays a
      role in cardiomyocyte differentiation during the early stages of development,
      whereas platelet-derived growth factor has a dedifferentiating effect.

PMID- 10971041
TI  - Simulated microgravity and hypergravity attenuate heart tissue development in
      explant culture.
AB  - Exposure to altered gravity may disturb the cytoskeleton-cell surface
      extracellular matrix (ECM) interface of embryonic cells. Development of organs
      such as the heart depends on dynamic interactions across cell surfaces.
      Fibronectin (FN), for example, a glycoprotein that links the ECM to the
      cytoskeleton through integrin surface receptors, is required for normal heart
      development. Thus, altered gravity may perturb organogenesis. We cultured
      precardiac explants from chick embryos in a rotating bioreactor vessel to
      simulate microgravity (microG), or in a tissue culture centrifuge, for 18 h
      during heart development. Bioreactor microG did not alter external morphology of
      explants, but did significantly reduce the proportion that developed
      contractions. Immunostaining for FN of explant sections showed that it also
      significantly reduced the linear extent of staining present in basement membrane
      regions. Analysis of ultrastructure revealed a significant reduction in the
      number of desmosomes per unit area and other differences. Hypergravity
      dramatically abolished development of contractions and altered morphogenesis. The
      results indicate a probable sensitivity of cardiomyogenic development involving
      FN to altered gravity.

PMID- 10971042
TI  - Light and electron microscopy of the bulbus arteriosus of the European eel
      (Anguilla anguilla).
AB  - The bulbus arteriosus of teleost fish acts as an elastic reservoir that dilates
      during ventricular systole to store a large part of the cardiac stroke volume.
      Despite its functional importance, the knowledge of the structure of the bulbus
      wall is still fragmentary. We have undertaken a series of studies in order to
      establish a general morphological plan of the teleost bulbus. The bulbus
      arteriosus of the European eel is studied here by means of conventional light,
      and transmission and scanning electron microscopy. The inner surface of the
      bulbus wall is irregular due to the presence of branching ridges that flatten and
      disappear toward the ventral aorta. The ridge surface is covered by flattened
      endocardial cells that show moderately dense bodies. In the ridge tissue, cells
      near the endocardium are mostly undifferentiated and appear isolated in a loose
      filamentous matrix. Ridge cells progressively cluster toward the middle layer,
      become surrounded by a dense matrix, and adopt characteristics typical of smooth
      muscle cells. This suggests the existence of a differentiation gradient. The
      middle layer is formed by typical smooth muscle cells embedded in a meshwork
      matrix that contains thin and thick filaments. Stretching of this meshwork
      suggests an active role of smooth muscle cells in bulbus wall dynamics.
      Furthermore, large areas of the extracellular space are occupied by elastin-like
      material. The amount of this material decreases toward the external layer.
      Collagen is demonstrated across the entire thickness of the bulbus wall, its
      amount and organization increasing from the inner toward the outer bulbus
      surface. The existence of matrix gradients should progressively increase wall
      strength, maintaining bulbus dilation within safe physiological parameters. The
      epicardium is formed by flattened cells that contain numerous pinocytotic
      vesicles, suggesting an active interchange of solutes with the pericardial
      cavity.

PMID- 10971044
TI  - Interspecies variation in axon-myelin relationships.
AB  - The primary objective of this paper was to determine the extent and nature of
      interspecies differences in axon calibre and myelin sheath thickness and in the
      various relationships between these. Morphometric analysis of the axon perimeter
      myelin sheath thickness relationship was performed on an equivalent nerve fibre
      population in a mammal, the rat, a bird, the chicken, an amphibian, the frog, a
      bony fish, the trout, and a cartilaginous fish, the dogfish. The abducent nerve
      was studied. It is especially suitable for this purpose because its fibres are
      closely similar in type and in peripheral distribution across the species
      studied. The relationship differed substantially between species. Differences
      were present in its setting, as described by the positions of the scatterplots,
      in the g ratio and in the regression and correlation data relating the
      parameters. Both parameters were markedly larger in the fish species than in all
      of the others. In addition, in rat, chicken, frog and trout, where large and
      small fibre classes could be differentiated clearly, the setting of the
      relationship between the two parameters was different for the two classes. In the
      main, variation in each of the parameters was greater between than within
      species. The larger fibres in the fish species were closely similar in axon
      perimeter and sheath thickness despite their long evolutionary separation. From
      this study and from others in the series, it may be concluded that there is no
      fixed or constant relationship between axon calibre and the thickness of the
      surrounding myelin sheath. Each nerve tends to have its own particular
      relationship and this differs between species.

PMID- 10971043
TI  - Chaperones in the parotid gland: localization of heat shock proteins in human
      adult salivary glands.
AB  - Heat shock proteins (HSPs) are expressed or increased in response to various
      biological stresses. Moreover, these 'stress proteins' seem to be expressed by
      some cells living in physiological conditions. From then on, they could play an
      important physiological role in normal cell functioning. The best-known
      physiological role of these HSP proteins is to act as 'molecular chaperones'. In
      this context, we have investigated the immunohistochemical expression of HSP27,
      HSP70, HSP90 and HSP110 in 10 human adult salivary glands. To highlight the
      presence of RNAm encoding HSP70, an in situ hybridization was performed. In our
      material, HSP27 was strongly expressed in the cytoplasm of striated duct cells
      and in some myoepithelial cells. The same localization was less stained for HSP70
      and HSP90. The immunocytochemical reaction was weak or negative for HSP110 in
      striated ducts. HSPs were not expressed in acinic cells. In situ hybridization
      gave a positive signal in striated ducts with a probe encoding HSP70. Epithelial
      cells of the striated ducts and myoepithelial cells expressed HSP27, HSP70 and
      HSP90. These HSPs probably act in part as molecular chaperones for protein
      synthesis, transport and for several interactions between HSPs and different
      proteins.

PMID- 10971045
TI  - Muscle sizes and moment arms of rotator cuff muscles determined by magnetic
      resonance imaging.
AB  - Biomechanical models which require information on, e.g., joint torque and muscle
      force are useful in the estimation of when and how mechanical overload of the
      musculoskeletal system may lead to disorders. The aim was to study the
      reliability and validity of magnetic resonance imaging (MRI) to quantify muscle
      sizes and moment arms by MRI and to test selected anthropometric measures as
      predictors of muscle sizes and moment arms. A total of 20 healthy Scandinavian
      women (age 22-58 years) participated in an MRI scanning of their dominant
      shoulder. With a PC-based program the reliability and the validity of the MRI
      measurements was estimated to be high, and mean anatomical cross-sectional areas
      (ACSA) and muscle lengths were measured to be 4.0, 9.8 and 12.1 cm(2) and 12.0,
      12.6 and 12.8 cm for m. supraspinatus, m. infraspinatus and m. subscapularis,
      respectively. Volumes were calculated to be 48.8, 125.1 and 153.6 cm(3). Moment
      arms were measured with the upper arm in a neutral position and in a functional
      position of 34 degrees abduction for m. supraspinatus only, and were 2.4 and 2.6
      cm. Physiological cross-sectional area (PCSA) and its fiber force component were
      estimated from dissected fiber length and pennation angle. MRI volume and PCSA
      were 1.4-1.7 times higher than dissection data, primarily because of age
      differences. No external anthropometric measures were found to be predictors of
      volumes or moment arms.

PMID- 10971046
TI  - Outcome measures in Alzheimer's disease: do they go far enough?
AB  - As the interest in Alzheimer's disease (AD) and its treatment has grown, so has
      the sophistication of clinical trials of potential drug therapies. In particular,
      interest has focused on outcomes used to assess the severity of the illness and
      the effectiveness of treatment. This paper reviews the assessments that are used
      frequently in trials of AD therapy and describes further measures that may be of
      value in determining effective treatments for the disease. The review concludes
      that it is important that evaluation of drug effects on AD is not confined solely
      to the assessment of cognitive function. To gain a true overview of the impact of
      AD on patients, carers and society, areas such as activities of daily living,
      caregiver burden, quality of life, behavioural symptoms and resource utilization
      need to be comprehensively determined.

PMID- 10971047
TI  - Allosteric modulation of nicotinic receptors as a treatment strategy for
      Alzheimer's disease.
AB  - Impairment of the central cholinergic system has a pivotal role in the cognitive
      decline observed in patients with Alzheimer's disease (AD). One of the most
      prominent cholinergic deficits is the reduced number of nicotinic acetylcholine
      receptors (nAChR) in the brain. Since these receptors are important for memory
      and learning, enhancing nicotinic neurotransmission is a promising treatment
      strategy for AD. The two most common approaches to correcting these cholinergic
      deficits are to increase the synaptic availability of acetylcholine (ACh) by
      inhibiting acetylcholinesterase (AChE), or to mimic the effects of ACh (nicotinic
      agonists) by acting directly on nicotinic receptors. Clinical studies suggest
      that AChE inhibitors produce only short-term symptomatic improvement. Similarly,
      long-term use of nicotinic agonists may induce desensitization of nicotinic
      receptors, leading to tolerance and therefore limiting the duration of efficacy.
      Allosteric modulation of nAChR is a novel approach, which circumvents the
      development of tolerance. Allosteric modulators bind to a site on nAChR that is
      different to the binding site of the natural agonist, ACh. This allosteric
      interaction amplifies the actions of ACh at post- and presynaptic nAChR. In
      particular, presynaptic nAChR are capable of modulating the release of ACh and
      other neurotransmitters, such as glutamate, serotonin and GABA, which may
      contribute to symptoms of the illness. Allosteric modulation of nAChR could
      therefore produce significant therapeutic benefit in AD. One of the most potent
      of these allosteric modulators is galantamine. As well as modulating nAChR,
      galantamine inhib- its AChE. The extent to which the clinical benefits of
      galantamine are attributable specifically to its nicotinic effects is uncertain
      and requires further investigation. However, galantamine maintains patients'
      level of cognitive and daily function for at least 1 year, which has not been
      reported for other AChE inhibitors. Galantamine's modulatory effects on nAChR may
      influence transcriptional regulation, resulting in an increased synthesis of
      nAChR. This may account for galantamine's sustained efficacy.

PMID- 10971048
TI  - Galantamine: additional benefits to patients with Alzheimer's disease.
AB  - Galantamine, a novel treatment for Alzheimer's disease (AD), has a dual mechanism
      of action, combining allosteric modulation of nicotinic acetylcholine receptors
      with reversible, competitive inhibition of acetylcholinesterase. In the Phase III
      clinical trial programme, over 3,000 patients with mild-to-moderate AD were
      enrolled in one of five randomized, controlled, double-blind studies. Using the
      Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) to assess
      memory and other cognitive functions, galantamine was found to be significantly
      superior to placebo in all five studies at doses of 16, 24 and 32 mg/day. In all
      studies, galantamine-treated patients maintained their cognitive function,
      whereas the placebo-treated patients experienced a significant deterioration in
      ADAS-cog scores. The 32-mg/day dose was not associated with any additional
      cognitive benefit. Pooled data from two 6-month studies (n = 1,269), which were
      of identical design, show that the therapeutic benefits of galantamine are
      sustained for the duration of treatment. The treatment effect (galantamine
      placebo difference on ADAS-cog) for the pooled data was approximately 4 points.
      Clinical benefit was seen in all levels of disease severity, with a 7-point
      advantage over placebo on ADAS-cog for patients with moderately severe disease.
      Galantamine was well tolerated, with most patients completing the 6-month
      studies. The long-term effects of galantamine have been evaluated in a 12-month
      study. Patients who completed one of the pivotal 6-month studies (n = 353) were
      entered into a 6-month open-label extension. Cognitive and daily function were
      maintained throughout the 12 months in patients who received galantamine 24
      mg/day. This sustained level of benefit may reflect galantamine's dual effect on
      the cholinergic system. Data from a 5-month, placebo-controlled study have also
      shown that galantamine produces significant benefits on behavioural symptoms. The
      persistence and range of therapeutic effects produced by galantamine suggest that
      it may provide additional benefits for patients with AD.

PMID- 10971049
TI  - Galantamine: therapeutic effects beyond cognition.
AB  - Decline in cognitive function, especially memory, is the core feature of
      Alzheimer's disease (AD). However, other characteristic aspects of the disease
      are also important. These include patients' activities of daily living (ADL),
      including quality of sleep, behavioural disturbances and the impact of the
      disease on the caregiver. Therefore, increasing attention is being paid to
      clinically meaningful outcome measures, such as the Disability Assessment for
      Dementia (DAD) scale, the Neuropsychiatric Inventory (NPI), caregiver time and
      the Pittsburgh Sleep Quality Index (PSQI). Galantamine is a new treatment for AD
      that combines modulation of nicotinic receptors with inhibition of
      acetylcholinesterase. The present review outlines the positive and sustained
      effects of this agent on patients' behaviour and daily functioning as well as on
      caregiver time. In studies of up to 5 months' duration, galantamine-treated
      patients had a significantly better outcome on ADL than placebo-treated patients,
      and after 12 months of treatment with galantamine, patients' functional ability
      was preserved. Galantamine also significantly benefits behavioural disturbances
      in patients with AD. These functional and behavioural benefits are associated
      with a decrease in the burden on caregivers, as indicated by a reduction,
      relative to placebo, in the time spent supervising and assisting patients. These
      clinical benefits are not offset by disruption of patients' sleep, as has been
      reported with other cholinergic treatments.

PMID- 10971050
TI  - The Dabska tumor: a thirty-year retrospect.
AB  - The Dabska tumor is a rare low-grade angiosarcoma also known as malignant
      endovascular papillary angioendothelioma of childhood. It primarily affects the
      skin of children and has a distinctive histologic pattern of anastomosing
      vascular channels with intravascular papillary outpouchings projecting,
      sometimes, in a glomerulus-like pattern, into a lumen lined by atypical columnar
      endothelial cells. Since its original description 30 years ago by one of us,
      knowledge in this area has expanded.

PMID- 10971051
TI  - No correlation of tyrosinase mRNA in bone marrow with prognosis of metastatic
      melanoma.
AB  - BACKGROUND: Recent publications suggest that tyrosinase mRNA in blood as well as
      in bone marrow is detectable only in a subgroup of patients with metastatic
      melanoma. OBJECTIVE: We addressed the question, whether patients with metastatic
      melanoma and with RT-PCR-detectable tyrosinase mRNA in blood or bone marrow have
      a different prognosis compared to tyrosinase mRNA-negative patients. METHODS: 20
      melanoma patients with widespread clinical metastases were enrolled and the
      survival time after first diagnosis of visceral metastases was correlated to
      tyrosinase mRNA presence in blood and bone marrow samples. RESULTS: The time of
      survival of 8 patients with metastatic melanoma and detectable tyrosinase mRNA in
      either blood or bone marrow was not different from the prognosis of 12 patients
      without detectable tyrosinase mRNA in either blood or bone marrow. CONCLUSION:
      Although based on a limited number of patients our results suggest that detection
      of tyrosinase mRNA in blood or bone marrow samples of melanoma patients with
      advanced disease seems to have no substantial relevance for survival time and
      outcome of disease. For this purpose, detection of tyrosinase mRNA by RT-PCR is
      not a valid tumor marker. Nevertheless, tyrosinase positivity in bone marrow in
      earlier tumor stages might indicate increased risk for the development of distant
      metastases. This should be addressed in further studies.

PMID- 10971052
TI  - Expressions of various growth factors and their receptors in tissues from
      neurofibroma.
AB  - BACKGROUND: Platelet-derived growth factor BB (PDGF-BB) and transforming growth
      factor beta are known to enhance the growth of neurofibroma-derived cells from
      neurofibromatosis type 1 (NF-1) patients. OBJECTIVE: This study aims to elucidate
      whether these growth factors and their receptors are up-regulated in NF-1
      patients. METHODS: Tissues and culture cells from neurofibroma in NF-1 patients,
      nontumor lesions in NF-1 patients, and the skin of normal controls were
      collected. To evaluate the expressions of growth factors and their receptors,
      reverse-transcriptase polymerase chain reaction and immunohistochemistry were
      performed. RESULTS: PDGF-beta receptor subunit was expressed in the neurofibroma
      tissues from NF-1 patients, but not in the nontumorous tissues from NF-1 patients
      or skin from normal controls. As for the other factors, there were no significant
      differences among these tissues. Neurofibroma sections also stained positive for
      the PDGF-beta receptor subunit. CONCLUSIONS: The interaction of PDGF and PDGF
      beta receptor subunit may be important in the tumorigenesis of NF-1.

PMID- 10971053
TI  - Changes in keratin 6 and keratin 10 (co-)expression in lesional and symptomless
      skin of spreading psoriasis.
AB  - BACKGROUND: Keratin 6 (K6) and keratin 10 (K10) are markers for epidermal
      hyperproliferation and differentiation, respectively, and are both expressed in
      the suprabasal layers of the epidermis. They may be co-expressed in different
      stages of the spreading psoriatic lesion, but single expression can also occur.
      OBJECTIVE: To investigate to what extent keratinocytes express K6 and K10, and to
      what extent they co-express K6 and K10 in different stages of the psoriatic
      lesion. We studied this in spreading psoriatic plaques. METHODS: Three 3-mm punch
      biopsies were obtained from the inner involved margin of a spreading lesion, from
      the uninvolved skin immediately adjacent to the spreading plaque, and from the
      distant uninvolved skin of 8 patients with incipient psoriasis. From 9 healthy
      volunteers, 3-mm punch biopsies were obtained as controls. After preparation of
      single cell suspensions of these biopsies, a triple staining protocol was
      performed with markers for K6 (monoclonal antibody LHK6B), K10 (monoclonal
      antibody RKSE60) and DNA content (TO-PRO-3 iodide). Subsequently, cells were
      measured with a flow cytometer and the proportion of the markers was calculated
      using specific software. RESULTS: We observed a population of K6/K10-co
      expressing cells, but also populations expressing only K6. These subpopulations
      varied with the involvement of the lesion. There was a statistically significant
      difference between the inner margin and the outer margin with respect to the
      proportion of K6- and K10-expressing cells, whereas more K6-positive and K10
      negative cells were detected in the inner margin of the lesions. The proportion
      of K6/K10-co-expressing cells in the inner margin was significantly different
      from the distant uninvolved skin. CONCLUSION: We confirmed that individual
      keratinocytes in psoriasis can express K6 or K10 depending on their localization
      in involved or uninvolved skin. There is a unique subpopulation of cells in the
      psoriatic plaques which co-express K6 and K10. More studies are required to fully
      understand the pathogenic relevance of co-expression and single expression of K6
      and K10.

PMID- 10971054
TI  - Mycosis fungoides: review of epidemiological observations.
AB  - BACKGROUND: Mycosis fungoides (MF) is a chronic cutaneous T-cell lymphoma
      characterized by small cells with cerebriform nuclei that usually express a
      mature peripheral T-helper cell (CD4+) immunophenotype. Its evolution is
      typically quite slow, with years between the first manifestations and development
      of advanced stages of disease. OBJECTIVE: The purpose of the present paper is to
      contribute to the material about MF already present in the literature. The review
      articles that have appeared to date fundamentally address the morphological
      characteristics, diagnostic criteria and treatment of the disease; in contrast,
      the present study centers on the evolution of the incidence of MF and on the
      knowledge of the possible risk factors implicated in its development. METHODS:
      Review of published papers about MF epidemiology. RESULTS: The evidence suggests
      that the incidence is increasing, but this may be artifactual due to improved
      diagnostic techniques. The risk of MF is limited to gender and race, being higher
      in males and in blacks. Survival is highly stage dependent, but 90% of patients
      survive 15 years with only 10% of cutaneous involvement. Few risk factors have
      been identified, but several studies have found an association with industrial
      exposure, particularly to oils. CONCLUSION: MF is a rare disease and its risk
      factors have not been studied in any great detail. A European case-control study
      in progress will substantially increase the evidence available and progress
      towards identifying a prevention strategy.

PMID- 10971055
TI  - Airborne occupational allergic contact dermatitis from triglycidyl-p-aminophenol
      and tetraglycidyl-4,4'-methylene dianiline in preimpregnated epoxy products in
      the aircraft industry.
AB  - BACKGROUND: Very little is known about allergic contact dermatitis (ACD) from
      preimpregnated epoxy products (prepregs). OBJECTIVE: To describe a patient with
      occupational ACD from prepregs, and report new quantitative data on the content
      of prepregs. METHODS AND RESULTS: A laminator developed work-related vesicular
      hand dermatitis. He worked in an aircraft plant assembling aircraft parts, being
      exposed to preimpregnated carbon fiber and fiberglass sheets (prepregs), and
      epoxy adhesive tapes and foams. Triglycidyl-p-aminophenol (TGPAP; 1-0.25%, 2+;
      0.05%, 1+) and tetraglycidyl-4,4'-methylene dianiline (TGMDA; 1%, 3+; 0.5-0.05%,
      2+) provoked allergic patch test reactions, whereas o-diglycidyl phthalate was
      negative (1-0.05% pet) and standard epoxy provoked a weak (?+) reaction. Six
      prepreg products provoking allergic patch test reactions were analyzed for their
      TGPAP, TGMDA and diglycidyl ether of bisphenol A (DGEBA) content using gas and
      liquid chromatographic methods, showing up to 10% of TGPAP, 19% of TGMDA and 5%
      of DGEBA in the prepregs. An epoxy primer contained 61% of TGPAP. CONCLUSION:
      TGPAP and TGMDA caused occupational ACD. These chemicals need to be used when
      patch testing patients are exposed to prepregs, because patch testing with DGEBA
      may be negative.

PMID- 10971056
TI  - High body mass index, dry scaly leg skin and atopic conditions are highly
      associated with keratosis pilaris.
AB  - BACKGROUND: In a previous study we have found that young patients with insulin
      dependent diabetes mellitus had a higher prevalence of keratosis pilaris (KP)
      than healthy controls, with a high correlation with body mass index (BMI) and
      ichthyosiform skin changes of the legs. OBJECTIVES: To investigate whether BMI,
      dry scaly legs and atopic conditions could be associated with KP in a healthy
      population of adolescents. METHODS: A total of 202 Jewish adolescents chosen at
      random among students undergoing a routine medical examination at school
      participated in the study. The patients filled in a questionnaire for data on
      ethnic origin, the presence or history of allergic rhinitis, asthma or atopic
      dermatitis, the presence of thyroid disease, diabetes or dry skin. A similar
      questionnaire was sent to the family physician for verification. A general
      inspection of the skin was made for the presence of KP; the lower legs were also
      examined for dry scaly skin and ichthyosiform skin changes. RESULTS: KP was
      present in 33 examinees (16%). Factors significantly associated with were dry
      scaly skin (p < 0.001, odds ratio, OR = 31.3, with 95% confidence interval, CI,
      6.4-153.7), BMI >25 (p < 0.001, OR = 4.9, with 95% CI 2.2-11.2) and atopy (p =
      0.001, OR = 4.5, with 95% CI 1.8-11.1). CONCLUSION: It therefore appears that KP
      is associated with multiple factors, including high BMI, leg skin dryness and
      atopic conditions.

PMID- 10971057
TI  - Adamantiades-Behcet's disease: serum IL-8 is a more reliable marker for disease
      activity than C-reactive protein and erythrocyte sedimentation rate.
AB  - BACKGROUND: Interleukin 8 (IL-8) has recently been under focused investigation
      because of its possible participation in the evolution of Adamantiades-Behcet's
      disease. OBJECTIVE: The reliability of IL-8 as a serological marker for the
      activity of the disease was investigated in a prospective consecutive trial of 34
      cases. METHODS: The activity of the disease was clinically evaluated by the
      number of actively involved organ systems registered on the day of blood sampling
      and by the presence of oral aphthous ulcers. Serum IL-8 levels were compared to C
      reactive protein (CRP) values and the erythrocyte sedimentation rate. RESULTS: An
      association of IL-8 levels with the activity of the disease was detected when
      compared with both the number of active clinical signs (p = 0.024) and the
      presence of oral aphthous ulcers (p = 0.002). In contrast, no association of CRP
      and sedimentation rate with the activity of the disease could be detected. A weak
      correlation of IL-8 levels with sedimentation rate values at 2 h was found (R =
      0.37, p = 0.032). CONCLUSION: Our results confirm previous data concerning the
      significance of IL-8 and, in addition, they provide first evidence for the
      reliability of IL-8 as a serological marker for assessment of the activity of
      Adamantiades-Behcet's disease in the follow-up of clinical and therapeutic
      studies.

PMID- 10971059
TI  - Extreme UV exposure of professional cyclists.
AB  - BACKGROUND: The most important risk factor for the development of melanoma and
      non-melanoma skin cancer is thought to be ultraviolet (UV) radiation. To date
      there is no quantification of the UV exposure of outdoor sports professionals
      training and competing at high solar UV levels. METHODS: During eight stages of
      the 'Tour de Suisse' cycling race, the UV exposure of 6 professional cyclists was
      monitored with Bacillus subtilis spore film dosimeters. RESULTS: The measurements
      showed a personal UV exposure between 0.2 minimal erythema dose (MED) during the
      prologue and 17.2 MED during a mountain stage. The mean daily personal exposure
      of all full stages (prologue excluded) was 8.1 MED. The personal exposure level
      determined during these races exceeded international exposure limits by more than
      30 times. CONCLUSION: Therefore UV exposure of sports professionals should be
      limited by application of sun screens, protective clothing and
      training/competition at low insolation.

PMID- 10971058
TI  - Long-term effects of interferon alpha 2A treatment in Behcet's disease.
AB  - BACKGROUND: Between May 1995 and April 1996, 20 patients with Behcet's disease
      were successfully treated with interferon alpha(2a) (IFN-alpha(2a)) 9 million
      IU/day three times a week and 16 patients with colchicine 1.5 mg/day orally for 3
      months. OBJECTIVE: To study the long-term effects of IFN treatment in Behcet's
      disease. METHODS: Between the years of 1996 and 1999, the patients were followed
      up every 3 months or whenever indicated. Retrospective evaluation was performed.
      RESULTS: In 56% of the patients with complete remission or partial remission at
      the end of IFN-alpha(2a) treatment, long-term remissions ranging from 36 to 48
      months were observed. CONCLUSION: IFN-alpha(2a) treatment is an effective
      treatment modality in Behcet's disease with the advantage of inducing prolonged
      remissions.

PMID- 10971060
TI  - Mucocutaneous junctional and flexural paresthesias caused by the holoplanktonic
      trachymedusa Liriope tetraphylla.
AB  - Multiple stages of Liriope tetraphylla caused paresthesias leading to chafing and
      excoriations in swimmers along the Southern Uruguayan and Northern Argentinean
      Atlantic coasts. These episodes appear seasonally in the summer and affect groups
      of bathers in shallow water (1-3 m).

PMID- 10971061
TI  - Renbok phenomenon in alopecia areata.
AB  - We present a second case of alopecia areata sparing a congenital nevus of the
      eyebrow. This inverse counterpart of perinevoid alopecia is discussed and placed
      in context to the recently described Renbok phenomenon. According to the present
      definition of a nevus as a genetic mosaic, a genetically determined resistance to
      alopecia areata is suggested in our case.

PMID- 10971062
TI  - New type of epidermal nevus syndrome.
AB  - An uncommon type of epidermal nevus characterized by systematized bands of non
      epidermolytic hyperkeratosis with increased hairiness and follicular
      hyperkeratosis was observed in a 16-year-old boy who showed, in addition,
      hemihypoplasia of limbs, brachydactyly, clinodactyly and onychodystrophy. This
      case cannot be categorized within the group of presently established epidermal
      nevus syndromes. Most likely, this combination of anomalies represents a new type
      of epidermal nevus syndrome.

PMID- 10971063
TI  - Parakeratosis variegata: a possible role of environmental hazards?
AB  - We report 2 cases of parakeratosis variegata (PV) evolving from lesions beginning
      with characteristics of ashy dermatosis. Both patients presented with a
      reticulated, poikilodermatous and hyperpigmented eruption with bizarre coalescent
      lichenoid papules. Histology showed lichenoid epidermotropic infiltrates, more
      pronounced in case No. 1, consistent with early malignancy. The course was
      chronic: after more than 10 years, systemic symptoms were not present. In patient
      No. 1, a monoclonal T-cell population was detected 12 years after the onset of
      the disease. Both patients had close contact with fertilizers and insecticides.
      In patient No. 2, the lesions spontaneously regressed within 3 years after
      cessation of exposure. PV may be a prelymphomatous stage of mycosis fungoides or
      some closely related cutaneous T-cell lymphoma and does not always evolve into
      overt malignancy. Gene rearrangement detection techniques may be helpful in
      predicting the course of the disease.

PMID- 10971064
TI  - A case of antiepiligrin cicatricial pemphigoid successfully treated by
      plasmapheresis.
AB  - We report the case of a 73-year-old Japanese woman suffering from antiepiligrin
      (laminin 5) cicatricial pemphigoid (CP) with typical clinical and
      immunopathological features. Histologically, the lesional mucous membrane showed
      a subepidermal blister formation. When indirect immunofluorescence techniques
      with skin split by 1 M NaCl as the substrate were used, the patient's serum
      reacted only to the dermal side. Immunoprecipitation studies demonstrated that
      the patient's serum contained IgG autoantibodies directed against a set of
      polypeptides that corresponded to epiligrin (laminin 5). After corticosteroids
      and immunosuppressive agents had been administered systemically, the patient's
      autoantibody titer decreased and the cutaneous and mucosal blister formations
      were suppressed. However, the ocular lesions persisted in spite of these
      therapeutic regimens. After combining these treatments with double-filtration
      plasmapheresis, the ocular lesions improved and showed almost no progression.
      Plasmapheresis may thus present a new option for the treatment of CP.

PMID- 10971065
TI  - Occupational skin injury by hydrogen peroxide.
AB  - Hydrogen peroxide is widely used in products such as rocket fuel, bleaching
      preparations and topical disinfectants. Contact of hydrogen peroxide with the
      skin can cause severe skin damage. In this report, we describe a case of skin
      injury induced by hydrogen peroxide. The patient was a 34-year-old man working in
      a dry cleaning shop. While he was pouring 35% hydrogen peroxide, some of it
      accidentally splashed over his left shoulder and back, and then an erythema,
      purpura and vacuolar eruption, similar to bubble wrap, appeared on his left
      shoulder and down the left side of his back. Histologically, numerous vacuolar
      structures were observed in the epidermis, dermis and subcutaneous tissue.
      Coupled with the clinical features, these vacuolar structures were considered as
      'oxygen bubbles'. Subcutaneous emphysema was detected by chest X-ray examination.
      All skin eruptions rapidly healed without scarring by using a steroid ointment.
      As far as we know, this is the first time such clinical and histological features
      have been described

PMID- 10971066
TI  - Two cases of segmental multiple glomangiomas in a family: type 1 or type 2
      segmental manifestation?
AB  - Several autosomal dominant skin diseases may manifest cutaneous mosaicism. Two
      types of segmental arrangement can be distinguished: type 1 is characterized by
      segmental lesions with similar severity to that observed in the diffuse
      phenotype, the remaining skin being normal; type 2 is characterized by segmental
      lesions showing a major degree of severity and milder lesions diffusely arranged.
      Multiple glomus tumours have recently been included in the group of
      genodermatoses showing type 2 segmental involvement. A family with 2 cases of
      multiple glomangiomas arranged in a segmental fashion is reported. A 12-year-old
      girl presented multiple nodular glomangiomas on her right buttock and thigh, in a
      band-like distribution. A sister of her paternal grandfather showed plaque-like
      multiple glomangiomas on her left thigh and various glomangiomas on her right
      buttock and arm. No other family members were known to be affected. Two new cases
      of familial segmental multiple glomangiomas are reported, with the particularity
      that one of these exhibited type 2 segmental manifestation and the other type 1
      from a clinical point of view.

PMID- 10971067
TI  - Tufted angioma of adult onset, revealing abundant eccrine glands and central
      regression.
AB  - Tufted angioma (angioblastoma) usually occurs in infancy. Some lesions reveal
      proliferation of eccrine glands and some undergo spontaneous regression. We
      report a lesion from the left lateral chest of a 58-year-old male, which had
      appeared 5 years ago and gradually increased in size. Its color had faded out
      centrally. Histological examination showed many angiomatous lobules on the border
      of the lesion but few in the central portion. Abundant eccrine sweat glands,
      small venules and dense connective tissue were seen in both areas. The histology
      and the clinical course suggested that central regression occurred in the lesion.
      Out of 211 reported cases, we found 4 cases that had annular lesions spreading
      centrifugally. Though these lesions were not examined histologically, they were
      suspected to regress in the central portions. We suggest that central regression
      can rarely occur in tufted angioma.

PMID- 10971068
TI  - UVB photosensitivity due to ranitidine.
AB  - We describe a 62-year-old male with photosensitivity due to ranitidine. An oral
      challenge test after taking ranitidine with UVB irradiation was positive.
      Ranitidine-induced UVB photosensitivity was persistent even after cessation of
      the medication.

PMID- 10971069
TI  - Psoriasis and myeloperoxidase deficiency.

PMID- 10971070
TI  - Pityriasis-rosea-like eruption due to benfluorex.

PMID- 10971071
TI  - Treatment of idiopathic mucinosis follicularis with UVA1 cold light phototherapy.

PMID- 10971072
TI  - Multiple, large, polypoid infundibular (epidermoid) cysts in a cyclosporin
      treated renal transplant recipient.

PMID- 10971073
TI  - Fulminating multi-organ failure in a young woman caused by rapidly progressing
      melanoma metastases.

PMID- 10971074
TI  - Merkel cell carcinoma developing after bone marrow transplantation.

PMID- 10971075
TI  - Solar UV-protective properties of textiles.

PMID- 10971076
TI  - 82nd annual meeting of the swiss society for dermatology and venereology.
      september 14-16, 2000, basel

PMID- 10971077
TI  - Twin-twin transfusion syndrome: the 'Select' procedure.
AB  - OBJECTIVES: Twin-twin transfusion syndrome (TTTS) is associated with a high risk
      of perinatal morbidity and mortality. The condition results from intertwin
      vascular connections in the shared placenta. We report here a case of early,
      severe TTTS that failed to respond to serial amniocenteses and that was
      successfully treated by means of superselective laser coagulation. METHODS: A
      causative arteriovenous anastomosis was identified by means of prenatal
      obstetrical sonography, using color and spectral Doppler techniques. At
      fetoscopy, performed at 23 weeks' gestation, laser occlusion of only this
      connection was achieved. RESULTS: This therapeutic intervention resulted in rapid
      resolution of all evidence of TTTS and a successful pregnancy outcome, with
      subsequent delivery of 2 healthy infants at 33 weeks' gestation. CONCLUSIONS: The
      potentially fatal pathophysiology of TTTS was reversed by interruption of a
      single arteriovenous connection. We have termed this the sonographically
      evaluated, laser-endoscopic coagulation for twins ('Select') procedure.

PMID- 10971078
TI  - The effect of fetal hydrops on the rate of fall of hemoglobin after fetal
      intravascular transfusion for red cell alloimmunization.
AB  - OBJECTIVE: We aimed to assess whether there is a difference between hydropic and
      nonhydropic fetuses in the rate of fall of hemoglobin (Hb) following
      intravascular transfusions. METHODS: Eighty-three intravascular transfusions in
      34 fetuses were analyzed. The pretransfusion and posttransfusion Hb values, the
      gestational age, the volume of blood transfused, the number of days between
      transfusions and the rate of fall of Hb per day following a transfusion were
      assessed. Hb levels were expressed as multiples of standard deviation from the
      normal mean for gestational age. RESULTS: Eleven fetuses were hydropic at
      presentation and 23 were not. Twenty-three transfusions were undertaken in the 11
      fetuses while they were hydropic and 60 transfusions were performed in
      nonhydropic fetuses. Comparisons of transfusion variables between the two groups
      were performed both for the first transfusion only and also for the total number
      of transfusions. The rate of Hb fall per day following a transfusion was similar
      in the two groups on both comparisons. The posttransfusion Hb level tended to be
      lower and the intervals between transfusions were a little shorter in the
      hydropic group, but these differences were not statistically significant.
      CONCLUSION: The posttransfusion Hb tended to be lower in the hydropic fetuses,
      but the fall in Hb was not faster in these cases. Therefore, with a similar rate
      of daily Hb decline in both groups, the hydropic fetuses are expected to become
      anemic again sooner than the nonhydropic fetuses only because of the lower
      posttransfusion Hb. The timing of the next transfusion should therefore be based
      on the posttransfusion Hb and the normal predicted drop per day irrespective of
      the presence or absence of hydrops.

PMID- 10971079
TI  - 3D real-time imaging of the fetal heart.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical utility of a novel
      3D scanner system for real-time 3D fetal echocardiography. METHOD: In a
      prospective study, 13 single, healthy 20- to 24-week-old fetuses were examined
      with conventional 2D and real-time 3D echocardiography. The visualization rates
      and imaging quality of standard cardiac views were compared between both methods.
      RESULTS: The visualization rates of standard cardiac planes were found to be
      slightly increased and more easily obtainable in 3D imaging whereas the image
      quality showed better results with conventional 2D echocardiography. CONCLUSION:
      Our data show that real-time 3D fetal echocardiography can be considered a useful
      tool in the evaluation of the fetal heart with the necessity for further
      refinement of the resolution quality

PMID- 10971080
TI  - Creation of myelomeningocele in the fetal rabbit.
AB  - OBJECTIVE: Myelomeningocele is a neural tube defect resulting in an exposed
      spinal cord, which leads to irreversible neurologic damage at birth. We proposed
      development of a fetal rabbit model of myelomeningocele to study in utero spinal
      cord injury and repair strategies. METHODS: New Zealand white rabbits (n = 10) at
      22 days of gestation (term = 31 days) underwent laparotomy to expose the gravid
      uterus; a hysterotomy exposed the fetal hindlimbs and back. A three to four level
      lumbar laminectomy was performed, and the dura over the posterior spinal cord was
      removed. At 30 days of gestation, the does underwent C-section for fetal harvest,
      and total fetal number, length, weight, and the presence or absence of a spinal
      defect were recorded for all viable fetuses. RESULTS: All injured fetuses were
      smaller and weighed less than the nonoperated littermate controls, and histologic
      examination confirmed a spina bifida-like lesion of their spinal cords.
      CONCLUSIONS: We successfully created an exposed spinal cord defect in the fetal
      rabbit model similar to the lesion found in humans. Advantageous because of low
      animal cost, relatively large fetal size, multiple fetuses per pregnancy, and
      short total gestation, this model will allow us to study the mechanism of injury
      to the exposed spinal cord, and perhaps develop strategies to repair human
      myelomeningoceles.

PMID- 10971081
TI  - Salvage of a fetus with congenital high airway obstruction syndrome by ex utero
      intrapartum treatment (EXIT) procedure.
AB  - A fetus with congenital high airway obstruction syndrome (CHAOS) due to complete
      tracheal atresia was referred at 31 weeks of gestation after 12 weeks of massive
      hydrops. The fetus was delivered by the ex utero intrapartum treatment procedure
      allowing sufficient time while on placental support for bronchoscopy to confirm
      tracheal atresia and tracheostomy to secure the airway. His postnatal course was
      complicated by severe capillary leak syndrome secondary to hydrops, diaphragmatic
      paralysis, tracheobronchial malacia, and the need for chronic ventilatory
      support. The infant's tracheobronchial malacia resolved by 5 months of age and
      normal diaphragmatic function was restored at 9 months allowing him to be weaned
      from mechanical ventilation. He underwent tracheal reconstruction at 17 months of
      age. At follow up at 32 months of age he has a patent airway and is the first
      long-term survivor with CHAOS.

PMID- 10971082
TI  - Influence of alternative birth methods on traditional birth management.
AB  - BACKGROUND: Because of popular demand for more natural childbirth, a new concept
      was introduced in 1991 in our clinic. It consisted of careful monitoring and
      birth management, restrictive use of invasive methods, and free choice of
      different birth methods including waterbirths and other alternative birth
      methods. Our aim was to determine the influence of our new birth concept on the
      way women give birth and on the birth management in our clinic. METHODS: In a
      total of 9,418 births between 1991 and 1997 [new birth concept KSF (KSF =
      Kantonsspital Frauenfeld)], the changing pattern of birth methods and birth
      management in our clinic under the influence of the new birth concept were
      analysed. The results were compared to a historical group in our clinic, a total
      of 5,602 births from 1986 to 1990, and to data from a contemporary group from
      Swiss clinics, a total of 344,328 births from 1986 to 1997. FINDINGS: Our study
      shows that alternative birth methods are very popular. The waterbirth rates have
      risen steadily and stabilized at around 40-50% of the spontaneous births. The
      Maia-birthing stool births rates reached a peak of popularity in 1993 (23%) 5
      years after their introduction, dropping again to 10% of the spontaneous births.
      The bedbirth rates have stabilized at around 40% of the spontaneous births. Other
      birth methods such as standing, supported by a rope, on the mat or on all fours
      are much less popular. The impact of our new birth concept on different aspects
      of birth management differs greatly from one to another. The episiotomy rate has
      dropped from a previous rate higher than 80% to a rate lower than 15%. The
      caesarean section rate in our clinic (around 10%) has remained substantially
      below the Swiss average (around 15%). The rate of the spinal and epidural
      analgesia was maintained at a constant level, around 13%, while the Swiss average
      rates doubled and reached 23% in 1997. The induction and amniotomy rates as well
      as the use of oxytocin were not influenced by the new birth concept and are
      comparable to the Swiss average. CONCLUSION: Alternative birth methods and in
      particular waterbirths are very sought after. This popular pressure insisting
      upon less invasive, more natural birth management can be well integrated into the
      security-oriented way of thinking of classical medicine. In our clinic the
      general trend towards more invasive measures in birth management could be
      countered by the introduction of a new birth concept with alternative birth
      methods.

PMID- 10971083
TI  - Waterbirths: a comparative study. A prospective study on more than 2,000
      waterbirths.
AB  - BACKGROUND: Waterbirths were introduced in 1991 as part of a new birth concept
      which consisted of careful monitoring and birth management, restrictive use of
      invasive methods and free choice of different birth methods. METHODS: After the
      introduction of this new birth concept a prospective observational study was
      initiated. All parturients of the region give birth in our clinic without
      preselection, ours being the only birth clinic of the region. 2% of the
      parturients will be referred to a larger birth clinic (university clinic) mainly
      because of preterm births before the end of the 33rd week of pregnancy. Every one
      of the 7,508 births between November 1991, and May 21, 1997, was analyzed. In
      this article the birth parameters of mother and child in the most often chosen
      spontaneous birth methods will be compared to assess the safety of alternative
      birth methods in general and of waterbirths in particular. 2,014 of these 5,953
      spontaneous births were waterbirths, 1,108 were Maia-birthing stool births and
      2,362 bedbirths (vacuum extractions not included). RESULTS: The parity and age of
      the mother as well as the newborn's birth weight are comparable in all 3 groups:
      waterbirth, Maia-birthing stool, and bedbirths. An episiotomy was performed in
      only 12.8% of the births in water, in 27. 7% of the births on the Maia-birthing
      stool and in 35.4% of the bedbirths. These differences are statistically
      significant. In spite of the highest episiotomy rates, the bedbirths also show
      the highest 3rd- and 4th-degree laceration rates (4.1%), thus the difference
      between the rates for bedbirths and alternative births methods for severe
      lacerations is significant. The mothers' blood loss is the lowest in waterbirths.
      Fewer painkillers are used in waterbirths and the experience of birth itself is
      more satisfying after a birth in water. The average arterial blood pH of the
      umbilical cord as well as the Apgar scoring at 5 and 10 min are significantly
      higher after waterbirths. Infections of the neonate do not occur more often after
      waterbirths. No case of water aspiration or any other perinatal complication of
      the mother or child which might be water-related was reported. CONCLUSION:
      Waterbirths and other alternative forms of birthing such as Maia-birthing stool
      do not demonstrate higher birth risks for the mother or the child than bedbirths
      if the same medical criteria are used in the monitoring as well as in the
      management of birth.

PMID- 10971084
TI  - Prenatal diagnosis of body stalk anomaly at 9 weeks of gestation. Case report.
AB  - We report on a case of embryonic anomaly detected at 9 + 5 gestational weeks. The
      lower part of the embryo was located in the coelomic cavity. Lower extremities
      could not be depicted. The abdominal wall showed the appearance of omphalocoele.
      After termination of pregnancy at 10 weeks, autopsy confirmed the anomaly of the
      lower embryonic parts consistent with the diagnosis of body stalk anomaly. To our
      knowledge, this is the first observation of this condition before 10 gestational
      weeks.

PMID- 10971085
TI  - A fetus with Prader-Willi syndrome showing normal diurnal rhythm and abnormal
      ultradian rhythm on heart rate monitoring.
AB  - Clinical features of Prader-Willi syndrome in neonates are marked hypotonia with
      the absence of crying and feeding difficulty so that prenatal diagnosis of Prader
      Willi syndrome is strongly hoped in order to provide appropriate medical and
      psychological care for neonates and their families. However, the clinical picture
      of Prader-Willi syndrome in utero has not been well described. We report a
      pregnancy associated with Prader-Willi syndrome manifesting polyhydramnios, large
      biparietal diameter of the fetus and characteristic fetal heart rate pattern:
      prolonged inactive periods and diurnal variation of the incidence of heart rate
      accelerations. These findings may offer a clue to the prenatal diagnosis of
      Prader-Willi syndrome, although molecular cytogenetics is mandatory for the
      definite diagnosis.

PMID- 10971086
TI  - Fetal-placental and decidual-placental units: role of endocrine and paracrine
      regulations in parturition.
AB  - In primates, fetal adrenal and placental steroidogenic enzymatic systems are
      complementary in a fetal-placental unit, synchronizing fetal maturation and
      myometrial activation in late gestation. Moreover, as hemochorial placentation
      characterizes rodents and primates, paracrine regulations between decidua and
      placenta are essential to the immunotolerance of the conceptus and its
      development. Thus, the decidual-placental unit remains in a striking state of
      decidual quiescence throughout gestation, and the reversal of this quiescence is
      thought to play a key role in myometrial stimulation and the onset of
      parturition. A comprehensive view of the control of myometrial contractility,
      through the interaction of paracrine and endocrine modifications in late
      gestation, is proposed. The failure of these mechanisms underlie prematurity and
      the use of fetal therapy in threatened preterm labor.

PMID- 10971087
TI  - [Effect of transdermal versus oral estradiol administration on the excretion of
      vasoactive markers in postmenopausal women].
AB  - OBJECTIVES: Can transdermal (n=20) and oral (n=20) estradiol substitution
      influence the urinary excretion of vasoactive substances in postmenopausal women?
      METHOD: The vasoactive substances prostacyclin and thromboxane, cyclic guanosine
      monophosphate, which can reflect the systemic NO production, serotonin, relaxin,
      insulin and melatonin were measured in nocturnal 8-hour urine before and after 2
      and 4 weeks' estradiol treatment. RESULTS: The excretion ot prostacyclin and
      thromboxane, calculated as a prostacyclin/thromboxane quotient, was shifted
      towards higher prostacyclin production. Only minor changes could be registered
      for the cyclic guanosine monophosphate excretion. The production of serotonin,
      relaxin and insulin was increased only after transdermal treatment with
      estradiol. For melatonin no changes could be observed. CONCLUSIONS: Hormone
      substitution therapy with estradiol in postmenopausal women is able to increase
      the urinary excretion of various vasoactive substances, both after transdermal
      and oral application, indicating a vasodilatory estrogenic action. Transdermal
      administration was more effective, although lower dosages were applied. An
      explanation may be that transdermal estradiol elicits continuous and constant
      effects on estrogenic target organs.

PMID- 10971088
TI  - [Postpartum footdrop due to compression of the lumbosacral trunk].
AB  - We report on a rare peripartal neuropathy of the leg caused by pro longed
      difficult labor in which forceps were used or caesarean sec tion was performed.
      Immediately after delivery, the 2 patients corn plained of a unilateral footdrop
      and numbness in the leg. The foot drop was most likely due to a compression of
      the lumbosacral trunl exposed to the fetal head. This trunk contains fibres from
      the lumba roots L4 and L5 and connects the lumbar with the sacral plexus. The
      outcome was favourable in both patients. If subsequent pregnancies occur,
      caesarean section may be indicated.

PMID- 10971089
TI  - [Guideline for the diagnosis of postmenopausal bleeding. PMPB Working Group of
      the SGGG].
AB  - 2.1. History and clinical-gynecological investigation including a Pap smear are
      the first step in the clarification. The history should make sure if there is in
      fact bleeding from the genital and not from the urological or the intestinal
      region. Drug intake should be recorded, and risk factors for the development of
      endometrial carcinoma should be considered. This will not affect further
      investigation. The clinical-gynecological investigation should prove the source
      of postmenopausal bleeding according to the anatomical site--uterine, infra-, or
      suprauterine. The causes of infrauterine bleeding may easily be diagnosed by
      means of inspection of the external genitalia and further by using a speculum.
      The causes of uterine bleeding are of major importance. Cytology and colposcopy,
      supported by bimanual investigation, exclude cervical carcinoma as a cause of
      bleeding. Atypical endometrial cells on the cytological smear arouse suspicion of
      endometrial carcinoma. 2.2. Transvaginal sonography (TVS) is the next step if the
      above-mentioned investigations are negative. Both adnexa should always be
      investigated and the findings sonographically documented, so that solid cystic
      masses in the adnexal area can be better identified as suprauterine causes of
      postmenopausal bleeding. Then the uterus should be investigated. Further
      procedures are decided from the results of measurement of the longitudinal
      section of the endometrium at the level of maximum endometrial thickness. If the
      endometrial thickness is _<4 mm, an observant attitude can be assumed. After 3
      months the patient should be controlled against using TVS. If bleeding recurs or
      the endometrial thickness is >4 mm on TVS, the procedure given in subparagraph
      2.3 should be followed. In case the endometrial thickness is >4mm or not
      measurable, a histomorphological investigation according to subparagraph 2.3
      should be performed. In such cases, saline infusion sonohysterography(SIS) is
      useful as a simple method to supplement TVS. It can aid in the decision making as
      to which further, more invasive measures should be taken (endometrial
      biopsy/hysteroscopic resection). Computerized tomography or magnetic resonance
      imaging are, as a rule, not indicated in patients with postmenopausal bleeding.
      2.3. A definite diagnosis is possible only on the basis of a histological
      investigation. If TVS or SS show evidence of a polypoid state, removal under
      hysteroscopic control is the diagnostic method of choice. In cases of symmetrical
      or asymmetrical thickening of the endometrium on SIS, a less invasive biopsy may
      be sufficient. If the biopsy specimen does not yield representative diagnostic
      material, one should proceed as described above. A fractionated curettage should
      as a rule not be performed solely, but in combination with hysteroscopy.

PMID- 10971090
TI  - Role of growth factors in the development of diabetic complications.
AB  - The structural changes characterising diabetic microangiopathy, which may be
      referred to as 'abnormal growth' and 'impaired regeneration', strongly suggest a
      role for a number of aberrantly expressed growth factors, possibly acting in
      combination, in the development of these complications. This initial speculation
      has been supported by the detection of increased concentrations of several growth
      factors in the target tissues of diabetic long-term complications, and by
      enhanced expression of these growth factors consequent to the activation of the
      biochemical pathways linking hyperglycaemia to microvascular changes: the polyol
      pathway; non-enzymatic glycation of proteins; vasoactive hormones; oxidative
      stress, and hyperglycaemic pseudohypoxia. As to nephropathy, insulin-like growth
      factor I (IGF-I) seems to be implicated in the earlier stages of the disease,
      while transforming growth factor beta (TGF beta) is involved both in the early
      and later stages, being responsible, at least in part, for extracellular matrix
      (ECM) accumulation. Vascular endothelial growth factor (VEGF) plays a pivotal
      role both in non-proliferative and proliferative retinopathy. Finally, deficiency
      of several neurotrophic factors, namely nerve growth factor (NGF) and IGF-I has
      been related to the degeneration or impaired regeneration occurring in diabetic
      neuropathy. Knowledge of the involvement of growth factors in diabetic
      microangiopathy opens the way to new therapeutic interventions aimed at blocking
      the deleterious actions of several growth factors.

PMID- 10971091
TI  - Determination of 17-hydroxyprogesterone in plasma by stable isotope
      dilution/benchtop liquid chromatography-tandem mass spectrometry.
AB  - An assay based on stable isotope dilution liquid chromatography-tandem mass
      spectrometry (ID/LC-MS-MS) was developed for the quantification of 17
      hydroxyprogesterone, the most important indicator of 21-hydroxylase deficiency in
      human plasma. Plasma was extracted using ethyl acetate and Extrelut columns. LC
      was performed on a reversed-phase C18 column using a water/methanol gradient. A
      benchtop triple quadrupole mass spectrometer, operating in selected reaction
      monitoring mode, served as mass detector. The analytical run time was 9 min per
      sample. The sensitivity was high: 0.06 pmol of 17-hydroxyprogesterone yielded a
      signal-to-noise ratio of 13. Precision (CV) and accuracy (relative error) derived
      from the analyses of unspiked and spiked validation samples were 7.4-12.0% and
      6.4%, respectively. When analyzing the same samples - median (range), in
      nanomoles per liter - from neonates and adults independently by ID/LC-MS-MS as
      well as by ID/gas chromatography (GC)-MS, corresponding results were obtained:
      neonates (n = 10), ID/LC-MS-MS 3.99 (0.48-16.05), ID/GC-MS 5.39 (1.57-13.02);
      adults (n = 10), ID/LC-MS-MS 2.66 (1.39-6.15), ID/GC-MS 2.54 (0.51-5.12). The
      technique permitted reliable detection of classical and nonclassical forms of 21-
      hydroxylase deficiency. The much simpler sample preparation, the faster
      analytical run time and the operational ease possible with ID/LC-MS-MS permit a
      considerable increase of sample testing per day without compromising on
      analytical sensitivity and specificity. We expect that benchtop tandem mass
      spectrometry will open new avenues in clinical steroid analysis.

PMID- 10971092
TI  - Volumetric bone mineral density in young women with Turner's syndrome treated
      with estrogens or estrogens plus growth hormone.
AB  - To explore the effects of estrogen replacement therapy (ERT) and recombinant
      growth hormone (GH) treatment on bone mineral density (BMD) in Turner's syndrome,
      we assessed volumetric BMD (vBMD), which is less dependent on body and bone
      sizes, in these patients at final height. The areal BMD (aBMD) was measured in 26
      young women with Turner's syndrome (age range 17.5-25.0 years) by dual-energy X
      ray absorptiometry, and vBMD was calculated. Patients were subdivided as group 1
      (n = 12; ERT alone) and group 2 (n = 14; GH + ERT). Years of estrogen exposure
      were not different between the groups (group 1: 6. 4 +/- 1.5 years; group 2: 5.3
      +/- 1.7 years); in group 2, GH therapy was 5.3 +/- 1.4 years. Final heights were
      significantly higher in group 2 than in group 1 (148.1 +/- 3.0 vs. 142.0 +/- 2.8
      cm; p < 0. 0001) as well as aBMD (1.073 +/- 0.118 vs. 0.968 +/- 0.122 g/cm(2); p
      < 0.04). vBMD was higher in group 2 but not significantly different from group 1
      (0.374 +/- 0.030 vs. 0.358 +/- 0.027 g/cm(3); p = 0.169). aBMD was reduced with
      respect to the normative values in both groups (group 1: -1.97 +/- 1.04 SDS, p <
      0.0001 vs. 0; group 2: -0.93 +/- 1.01 SDS, p < 0.005 vs. 0), whereas vBMD was not
      (group 1: -0.07 +/- 0.79 SDS; group 2: 0.42 +/- 0.82 SDS). Our data suggest that:
      in Turner's syndrome GH administration improves final height and aBMD, but it
      does not significantly increase vBMD; aBMD reduction in Turner's syndrome is
      likely due to the impaired growth and reduced bone size; Turner's patients on ERT
      from adolescence show vBMD values in the normal range in young adulthood.

PMID- 10971093
TI  - Mutational analysis in Lebanese patients with congenital adrenal hyperplasia due
      to a deficit in 21-hydroxylase.
AB  - Molecular defects in the gene encoding steroid 21-hydroxylase (CYP21) result in
      impairment of adrenal steroid synthesis in patients affected with autosomal
      recessive congenital adrenal hyperplasias (CAH). In this study, we report on the
      molecular screening of six point mutations, large deletions, gene conversion
      events and duplications in 25 unrelated Lebanese families affected by CAH due to
      steroid 21-hydroxylase. The methods used (PCR-digestion and southern blot)
      allowed the detection of 96% of the disease chromosomes. In classical forms, the
      most frequent mutation was the splice site mutation in intron 2 accounting for
      39% of the disease alleles. Gene conversion events accounted for 14% of the
      alleles, but no large deletions were found. In nonclassical forms, the V281L
      mutation in exon 7 represent 86% of the tested alleles. Genotype-phenotype
      correlations were as expected: Delta 8nt, Q318X and gene conversion correspond to
      SW forms, whereas the intron 2 splice site mutation may give either SW or SV
      forms; the V281L mutation was responsible for nonclassical forms. The spectrum of
      mutations underlines the genetic diversity of the Lebanese population. No
      correlation could be drawn out between mutations and some specific religious
      communities, except for the Delta 8nt mutation, which is present only in the
      Christian Maronite group. Molecular study of the CYP21 gene might constitute a
      good support for clinicians, especially in consanguineous families, for whom we
      could provide genetic counselling.

PMID- 10971094
TI  - Response to treatment in patients with partial androgen insensitivity due to
      mutations in the DNA-binding domain of the androgen receptor.
AB  - The androgen insensitivity syndrome is a disorder caused by deficient function of
      the androgen receptor, characterized by varying degrees of undermasculinization
      in karyotypic males. We have identified four mutations in the androgen receptor
      gene, in the region encoding the DNA-binding domain of the protein. Two
      mutations, R607X and R615G, were found in patients with complete insensitivity to
      androgens, whereas the other two, S578T and A596T, were found in patients with
      partial insensitivity. The functional consequences of the three missense
      mutations were assayed in vitro after transient expression of the receptors in
      COS cells. All mutants showed normal androgen binding but abnormal abilities to
      stimulate transcription of an androgen-responsive reporter gene. R615G abolished
      transactivation whereas S578T and A596T were partially malfunctional. The
      function of A596T, but not of S578T, was normalized at high androgen
      concentrations in vitro, reflecting the in vivo situation. Thus, patients with
      specific mutations in the DNA-binding domain of the androgen receptor may benefit
      from androgen treatment.

PMID- 10971095
TI  - Idiopathic growth hormone deficiency: a vanishing diagnosis?
AB  - Some non-organic causes for growth hormone (GH) deficiency (GHD) can be
      attributed to genetic defects within the hypothalamo-pituitary axis. Using modern
      molecular biology techniques micromutations within the GH and GH-releasing
      hormone receptor genes have been detected as a rare cause of isolated GHD.
      Combined pituitary hormone deficiencies (CPHD), on the other hand, are associated
      with defects that manifest during the organogenesis of the anterior pituitary
      gland. In recent years an increasing number of patients with CPHD has been
      reported, showing mutations within pituitary transcription factors Pit-1, Prop-1
      and HesX1. Such defects can be observed with different frequencies in patients.
      Some disorders, such as CPHD due to Pit-1 mutations, display a hormonal phenotype
      that seems more or less invariable. In most other forms of genetic CPHD both the
      combination and severity of anterior pituitary hormone deficiencies vary
      considerably. Ongoing research concentrates on factors involved in the
      differentiation and proliferation of cells that belong to the hypothalamo
      pituitary growth axis. As not every possible candidate turns out to be a frequent
      cause of GHD or CPHD in humans, it will be many more years before the term
      'idiopathic' becomes a vanishing attribute to the clinical diagnosis of pituitary
      insufficiency.

PMID- 10971096
TI  - Activating and inactivating hormone receptor mutations.
AB  - The unravelling of gene structures of hormones, their receptors and the various
      components of their signal transduction apparatus has enabled diagnosis of the
      aetiology of hormone resistance at the molecular level. Inactivating mutations
      can be found in hormone receptor genes or those encoding components of the post
      receptor signal transduction cascade. Another category of receptor mutation is
      that causing constitutive receptor activation, which results in ligand
      independent, inappropriate or supraphysiological hormone action and in some cases
      malignant growth. The purpose of this contribution is to review the different
      types of inactivation and activation mechanisms that are induced by receptor
      mutations, using some of the best characterised mutations as examples. In
      addition, the currently known mutations of hormone receptors are briefly
      summarised.

PMID- 10971097
TI  - G protein defects in signal transduction.
AB  - G proteins couple receptors for many hormones to effectors that regulate second
      messenger metabolism. Several endocrine disorders have been shown to be caused by
      either loss- or gain-of-function mutations in G proteins or G protein-coupled
      receptors. In pseudohypoparathyroidism type Ia (PHP Ia), there are generalized
      hormone resistance (parathyroid hormone [PTH], thyroid-stimulating hormone,
      gonadotropins) and associated abnormal physical features, Albright hereditary
      osteodystrophy. Subjects with PHP Ib are normal in appearance and show renal
      resistance to PTH. In McCune-Albright syndrome (MAS), subjects show autonomous
      endocrine hyperfunction associated with fibrous dysplasia of bone and skin
      hyperpigmentation. Germline loss-of-function mutations have been identified in
      the G(s)-alpha gene in PHP Ia, and recent evidence suggests that the G(s)-alpha
      gene is paternally imprinted in a tissue-specific manner. Abnormal imprinting of
      the G(s)-alpha gene may be the cause of PHP Ib. MAS, in contrast, is caused by
      gain-of-function missense mutations of the G(s)-alpha gene.

PMID- 10971098
TI  - The role of estrogen in the male and female: evidence from mutations in synthesis
      and action.

PMID- 10971100
TI  - Diagnosis of growth hormone deficiency in childhood. On behalf of the Growth
      Hormone Research Society.

PMID- 10971099
TI  - Selective oestrogen receptor modulators.
AB  - Selective oestrogen receptor modulators (SERMs) are compounds which act like
      oestrogens in some target tissues but which antagonise their effects in others.
      The first example of a SERM (referred to as a first-generation compound) was
      tamoxifen, for which oestrogen-like agonist activity on bone was seen to occur
      simultaneously with oestrogen antagonist activity on the breast. An unwanted
      effect of tamoxifen was its oestrogen-like action on the endometrium. Second
      generation compounds have since been developed, most notably raloxifene, which
      has oestrogen-like actions on bone, lipids and the coagulation system, and
      oestrogen antagonist effects on the breast and uterus. Raloxifene has undergone
      very extensive, prospective, placebo-controlled, randomised trial evaluation, in
      which anti-fracture efficacy (to date only for vertebral fracture) has been
      accompanied by a major reduction in the incidence of new breast cancer. The
      compound is similar to placebo in its uterine effects, and similar to oestrogen
      in causing a two- to threefold increase in the risk of venous thromboembolism.
      Its lipid effects are similar to those of oestrogen, except for a relatively
      small effect on high-density lipoprotein cholesterol, and no significant effect
      on triglycerides. Data on cardiovascular event rates are not yet available; data
      on cognitive function are preliminary and, to date, reassuring. The mechanisms by
      which the same compound can exert oestrogen agonist effects on one target and
      antagonist effects on another are still being clarified. Important aspects
      include the fact that the oestrogen receptor undergoes different conformational
      changes according to the ligand. Thus the crystal structure of oestradiol bound
      to the oestrogen receptor differs from that of raloxifene bound to the same
      receptor. The existence of two oestrogen receptor subtypes may also be relevant.
      Mechanisms include differing interactions with various domains of the oestrogen
      receptor, and tissue-specific recruitment of steroid receptor co-activators and
      co-repressors may underlie some of the tissue-specific effects. The SERMs may be
      the prototype for other selective steroid receptor modulators, for example the
      androgen and progesterone receptors. The development of tissue target-specific
      agents is an exciting advance in endocrine pharmacology and can be extended to
      agents, such as tibolone, which exert some of their tissue specificity through
      their metabolites.

PMID- 10971101
TI  - New paradigms for growth hormone therapy in children.
AB  - Much has been learned over the last two decades regarding the management of
      growth hormone (GH) deficiency (GHD) in children and adolescents. However,
      significant divergence and debate continue to exist on the ideal approach to the
      management of GHD. Despite active controversy, several paradigms have recently
      emerged which should guide the treatment of GHD patients as we head into the new
      millennium. The primary objectives of GH therapy remain the normalization of
      height in childhood and the attainment of normal adult height, but the
      recognition of the metabolic roles of GH define additional therapeutic benefits.
      A daily subcutaneous injection of recombinant human GH in a dose range of 25-50
      microg/kg/day has been established as the mainstay of therapy. Alternative modes
      of treatment including GH-releasing hormone (GHRH), GH secretagogues and depot GH
      have been developed, but evaluation of their clinical utility remains incomplete.
      Careful monitoring and follow-up of pediatric GHD patients by a pediatric
      endocrinologist are essential. Accurate determination of height velocity and
      interval height increases (expressed as the change in height z score) continue to
      be the most important parameters in monitoring the response to treatment.
      Monitoring serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 has
      gained utility in the assurance of compliance and safety, but does not always
      correlate well with the growth response. A clear role for a biochemical as well
      as an auxological monitoring approach has nonetheless been established. The
      comparison of attained growth response to that which has been calculated by
      various modeling approaches is also becoming a valuable monitoring tool.
      Significant side effects of GH therapy are quite rare and are easily identified
      and addressed during close follow-up. Despite previous concerns, it now appears
      that in the absence of additional risk factors there is no evidence that long
      term recipients of GH are at any increased risk of developing diabetes, slipped
      capital femoral epiphysis, brain tumor recurrence or leukemia. Although GHD may
      or may not persist into adult life, adult GHD diagnostic criteria and the
      importance of GH therapy in adult GHD patients have recently been established.
      Therefore, the pediatric endocrinologist now has a crucial role in guiding the
      transition to adult GHD management in collaboration with the adult
      endocrinologist. In the years to come, with the continued investigation and
      collaborationof experts from around the world, the approach to GH treatment will
      undoubtedly continue to evolve and improve.

PMID- 10971102
TI  - Growth hormone - hormone replacement for the somatopause?
AB  - Twenty-four-hour growth hormone (GH) secretion reaches a peak at around puberty
      and by the age of 21 has begun to decrease. Thereafter the fall in GH secretion
      is progressive such that by the age of 60 most adults have total 24-hour
      secretion rates indistinguishable from those of hypopituitary patients with
      organic lesions in the pituitary gland. Patterns of GH secretion are similar to
      those in younger people but GH pulses are markedly reduced in amplitude. Sleep
      and exercise remain the major stimuli for GH secretion. The fall in GH secretion
      seen with ageing coincides with changes in body composition and lipid metabolism
      that are similar to those seen in adults with GH deficiency. In elderly subjects,
      although GH secretion is markedly reduced, remaining GH secretion correlates
      closely with body composition (particularly with lean body mass and inversely
      with central abdominal fat). Pioneering studies carried out by Rudman showed that
      GH administration to elderly subjects with low insulin-like growth factor-I
      levels resulted in reversal of many of the changes associated with GH deficiency,
      namely an increase in lean body mass and bone mineral density and a reduction in
      body fat and plasma cholesterol. These changes were remarkably similar to those
      shown a year earlier in adults with GH deficiency given GH replacement.
      Subsequent studies of GH replacement in elderly adults have confirmed Rudman's
      initial observations but have been dominated by side effects which have led to a
      high number of dropouts. It is now clear that the elderly are very sensitive to
      GH and the doses used need to be very low, increased very slowly and tailored to
      the individual needs of each patient. Using this more cautious approach, recent
      studies have been very positive. A series of papers from Blackman's group,
      presented at the US endocrine meeting in San Diego in 1999, investigated the
      effects of GH with or without testosterone supplements (in men) and oestrogen
      supplements (in women). Their results showed positive effects of GH on lean body
      mass, central fat, low-density lipoprotein cholesterol and aerobic capacity. In
      many instances there was a positive interaction between GH and hormone
      replacement with testosterone and oestrogen, but it appeared that GH showed the
      most potent anabolic effects. Clearly more studies are needed before GH
      replacement for the elderly becomes established. Safety issues will require close
      scrutiny, but the data available so far are sufficiently positive to undertake
      large multicentre, placebo-controlled trials, particularly looking at endpoints
      associated with prevention of frailty and loss of independence.

PMID- 10971103
TI  - The somatopause: to treat or not to treat?
AB  - There is much evidence that some aspects of ageing are similar to those observed
      in selective hormone deficiencies during adulthood. Replacement therapy in
      hypogonadism and/or growth hormone (GH) deficiency in adulthood is very
      successful in reversing the related clinical symptomatology. However, preliminary
      studies of GH treatment in the normal elderly have been largely disappointing: an
      increase in muscle mass is only accompanied by improved muscle strength if
      exercise is also increased during this period. No real benefit of GH therapy,
      additional to that of exercise, has been reported. Epidemiological studies
      indicate a relationship between high-normal insulin-like growth factor-I levels
      and cancer development. No definitive answers can presently be given regarding
      the safety of long-term GH therapy in otherwise healthy individuals during the
      somatopause.

PMID- 10971104
TI  - Is there growth hormone deficiency in prader-willi Syndrome? Six arguments to
      support the presence of hypothalamic growth hormone deficiency in Prader-Willi
      syndrome.
AB  - Prader-Labhart-Willi syndrome (PWS) is the most frequent form of syndromal
      obesity. Its main features are associated with hypothalamic dysfunction, which
      has not yet been comprehensively described. The aim of this review is to present
      arguments to define the presence of genuine growth hormone (GH) deficiency (GHD)
      in these patients. Decreasing growth velocity despite the onset of obesity,
      reduced lean body mass in the presence of adiposity, small hands and feet,
      relatively low insulin-like growth factor-I and low insulin levels, as well as
      the dramatic effect of GH treatment on growth, support the presence of
      hypothalamic GHD in PWS. Even though it might be difficult to ultimately prove
      GHD in PWS because of the obesity-induced counterregulation, the hormonal
      situation differs from that in simple obesity. The effects of long-term therapies
      with GH on body composition in these patients are summarized. GH therapy
      dramatically changes the phenotype of PWS in childhood: height and weight become
      normal and there is a sustained impact on the net loss of body fat. We conclude
      that GHD may account for several features of PWS.

PMID- 10971106
TI  - Hypophosphataemic rickets.
AB  - X-Linked hypophosphataemic rickets (XLH) is frequently associated with short
      stature even when conventional treatment (1, 25-dihydroxyvitamin D(3) or 1alpha
      hydroxyvitamin D(3) plus inorganic phosphate salts) is administered for a long
      time. The pathogenesis of growth retardation is probably multifactorial. Affected
      patients usually show normal growth hormone (GH) secretion. In some poorly
      growing XLH patients, long-term GH treatment associated with conventional therapy
      improves linear growth. GH treatment also increases phosphate retention but this
      effect is transient.

PMID- 10971105
TI  - Growth hormone therapy in achondroplasia.
AB  - Achondroplasia is one of the most common causes of severe rhizomelic dwarfism. We
      have previously reported the growth-promoting effect of growth hormone (GH) in
      this disorder. In this expanded clinical study, dose dependency and the long-term
      effect of GH were also investigated. Prepubertal children with achondroplasia (82
      males and 63 females) were randomly divided into 2 groups. Patients were treated
      with 0.5 IU/kg per week or 1.0 IU/kg per week subcutaneous recombinant human GH.
      Of 75 patients, the mutational analysis of fibroblast growth factor receptor-3
      revealed that G1138A was detected in 70 and G1138C was found in 2. GH increased
      growth rate and height z score in a dose-dependent manner. GH also increased
      serum insulin-like growth factor (IGF)-I, IGF-binding protein-3 and osteocalcin.
      No adverse effects were observed in either group. We conclude that GH therapy is
      a useful method for improvement of severe growth retardation of achondroplasia.

PMID- 10971107
TI  - Thickened pituitary stalk on magnetic resonance imaging in children with central
      diabetes insipidus.
AB  - Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk thickening
      (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI)
      due to infiltrative processes. Twenty-six children with DI and PST underwent
      cerebral MRI at the age of 8 +/- 4 years and were followed (n = 25) by clinical
      and MRI evaluation for 5.5 +/- 3.6 and 3.0 +/- 2 years, respectively, but given
      no treatment other than hormonal substitutive therapy. Patients were subdivided
      into groups according to the etiology of the DI: germinoma (n = 4), Langerhans'
      histiocytosis (n = 5) or 'idiopathic' DI with PST (n = 17). Complete anterior
      pituitary evaluation in 24 of the 26 patients revealed that 14 children were
      suffering from associated growth hormone deficiency and 7 had multiple hormone
      deficiencies. At the first MRI evaluation, pituitary stalk enlargement varied
      from 2.2 to 9.0 mm. The anterior pituitary gland was found to be normal (n = 12),
      small (n = 8) or enlarged (n = 6). At the final evaluation, a change in MRI
      features had occurred in 16 patients: morphological and/or signal changes in the
      PST (n = 16; 6 of whom showed an increase in PST) and changes in anterior
      pituitary gland size (n = 8; 3 of whom had increased and 5 had decreased). The
      presence of a growing suprasellar mass with a progressively enlarging pituitary
      stalk was demonstrated in the 6 patients who had shown increased pituitary stalk
      enlargement 1.8 +/- 1.6 years after the first MRI. In 4 of these patients, a
      diagnosis of germinoma was made 1.3 +/- 0.6 years after PST identification by MRI
      at the onset of DI, but the other 2 patients showing a suprasellar mass were
      still categorized as 'idiopathic' at the final clinical evaluation performed 7.8
      and 12.3 years after DI onset. In 10 patients (all but 1 with Langerhans'
      histiocytosis, showing 'idiopathic' DI) the pituitary stalk enlargement was
      diminished after 2.0 +/- 1.9 years of MRI follow-up, and there was a complete
      reversal of pituitary stalk enlargement in 5 patients. We conclude that the
      natural history of 'idiopathic' isolated central DI with PST is unpredictable.
      Although germinoma should always be considered during the first 3 years of follow
      up in patients presenting isolated DI with PST by repeated investigations every 3
      6 months, it remains an infrequent etiology, affecting only 15% of cases in our
      study.

PMID- 10971108
TI  - Management of pituitary tumours: strategy for investigation and follow-up.
AB  - Investigation of a patient presenting with evidence of a pituitary tumour has
      three main objectives: investigation of any hormonal hypersecretion; assessment
      of residual pituitary function, and examination of any mass effect of the tumour.
      A prolactin-secreting adenoma is often easily diagnosed by performance of a basal
      prolactin level. Biochemical assessment to exclude acromegaly or Cushing's
      disease should only be performed if clinically indicated. The standard
      investigations for acromegaly consist of establishing the degree of growth
      hormone (GH) suppression following a glucose load and estimating the basal
      insulin-like growth factor-I level. Before detailed investigation for Cushing's
      disease is initiated, the presence of Cushing's syndrome must be established. The
      second requirement is to determine the presence of any pituitary hyposecretion.
      Whilst the remainder of pituitary function can be assessed by baseline hormonal
      estimations, the evaluation of ACTH and GH secretion necessitates dynamic
      function testing. Lastly, the impact of the mass itself requires careful
      examination. Both neuroradiology, preferably magnetic resonance imaging at a
      centre specialized in examination of the pituitary fossa, and careful detailed
      clinical examination of the visual fields should be performed. The follow-up
      requirements in an individual patient are affected by a number of factors
      including the size and nature of the underlying tumour and any treatment
      administered. In patients with a hormone-secreting tumour, the hormone levels
      themselves provide a 'tumour marker' to aid follow-up. An important caveat,
      however, is that on some occasions tumour size and hormone levels do not change
      in parallel. Patients who have undergone pituitary surgery should have dynamic
      assessment of pituitary function performed approximately 6 weeks after surgery.
      There is no reason to suspect any further impairment of pituitary function after
      this date. In direct contrast, pituitary hormone deficiencies after radiotherapy
      are unlikely less than 6 months after treatment. Patients should undergo testing
      of pituitary reserve at 6 months, and then at yearly intervals for at least 10
      years after radiotherapy, if they have not already developed panhypopituitarism.
      Even after this period, if patients develop new symptoms the possibility of
      further pituitary hormone deficits should be considered. Neuroradiology should be
      performed approximately 6 weeks to 3 months after surgery. If radiotherapy is not
      administered, neuroradiology should be performed yearly for at least 10 years. If
      the patient has received radiotherapy, tumour recurrence is much less likely and
      therefore in these individuals neuroradiology does not need to be performed with
      such regularity. In conclusion, when planning the investigation and follow-up of
      an individual patient, one should take into account the size and characteristics
      of the tumour, as well as the treatment modalities.

PMID- 10971109
TI  - Pituitary surgery for the management of acromegaly.
AB  - Active acromegaly is almost always the result of a benign growth hormone (GH)
      secreting adenoma of the pituitary gland. Because the same pituitary stem cell
      can produce both GH and prolactin (PRL), many acromegalic patients also have
      hyperprolactinemia. The advantages of surgical excision of pituitary adenomas
      associated with acromegaly include: (1) prompt decrease in GH; (2) reliable and
      immediate relief of the mass effect from the tumor (decompression of the optic
      nerves and chiasm), and (3) the opportunity to obtain tumor tissue for
      characterization and investigative study. Currently, more than 97% of operations
      for removal of pituitary tumors associated with acromegaly are done using the
      transsphenoidal approach rather than craniotomy. Technical advances to make the
      surgery safer continue to evolve, and include endoscopic approaches, computer
      guided image-based intraoperative visualization, and intraoperative magnetic
      resonance imaging. Criteria for satisfactory remission of acromegaly after
      surgery are the same as those used for medical management. They include normal
      insulin-like growth factor (IGF)-I and suppression of GH to undetectable levels
      (<1.0 ng/ml) during an oral glucose tolerance test (OGTT). Data from a recent
      series of 86 patients operated upon for acromegaly at the University of Virginia
      and followed for more than 1 year have been reviewed. In patients receiving
      surgery as the initial procedure, 67% had a normal IGF-I, and 52% suppressed to
      <1.0 ng/ml in an OGTT. There was one true recurrence of disease diagnosed 81
      months after surgery. Results are best in patients with noninvasive
      microadenomas. Gamma knife radiosurgery has been a valuable adjunct in those
      patients who fail to achieve postoperative remission. Pathological evaluation of
      the tumors revealed that 16% expressed GH only, 25% stained for GH and
      glycoprotein hormones (follicle stimulating hormone, thyroid hormone, thyroid
      stimulating hormone, alpha-subunit), 21% for GH and PRL, and 33% for GH, PRL and
      glycoprotein hormones. There was one acidophil stem cell tumor and 10% had the
      mammosomatotroph subtype. This contemporary series was free of mortality or
      serious complications. One patient had a transient cerebrospinal fluid leak and 3
      developed transient SIADH with hyponatremia. Surgical treatment remains an
      important aspect of the combined management of patients with acromegaly.

PMID- 10971110
TI  - New medical approaches in pituitary adenomas.
AB  - Recently, the medical approach to patients with secreting and clinically non
      functioning pituitary adenomas has received great impulse thanks to the
      availability of new, selective and long-lasting compounds with dopaminergic
      activity, such as cabergoline, and of somatostatin analogues provided in slow
      release formulations, such as lanreotide and octreotide long acting release
      (LAR). In particular, the use of cabergoline has induced control of
      hyperprolactinaemia and tumour shrinkage in the great majority of patients with
      micro- and macroprolactinomas. Cabergoline treatment restores fertility both in
      women and men, and partially improves osteoporosis, one of the major
      complications of hyperprolactinaemia. In acromegaly, disease control (growth
      hormone [GH] <2.5-1.0 microg/l as a fasting or glucose-suppressed value,
      respectively, together with age-normalised insulin-like growth factor [IGF]-I) is
      achievable in more than half of patients receiving treatment with lanreotide or
      octreotide-LAR. Improvement in cardiomyopathy, sleep apnoea and arthropathy has
      been reported during GH/IGF-I suppression after pharmacotherapy. A synthetic GH
      analogue, B2036-PEG, that antagonises endogenous GH binding to its receptor
      binding sites and a GH-releasing hormone antagonist that blocks the effect of
      this releasing factor on the hypothalamus and pituitary are presently under
      investigation in acromegaly. Preliminary studies have clearly demonstrated the
      effectiveness of the GH receptor antagonist in suppressing IGF-I levels in
      acromegalic patients previously unresponsive to somatostatin analogues.
      Beneficial effects of subcutaneous octreotide and lanreotide have also been
      reported in adenomas secreting thyroid-stimulating hormone, while the results of
      treatment with dopamine agonists or somatostatin analogues remain disappointing
      in patients with clinically non-functioning adenomas. In these patients the
      possibility of visualising in vivo the expression of D(2) receptors using
      specific radiotracers such as (123)I-methoxybenzamide has allowed selection of
      patients likely to respond to cabergoline. Scant effects of pharmacotherapy have
      also been reported in patients with adenomas secreting adrenocorticotropic
      hormone. However, some preliminary data suggest a potential use of cabergoline in
      combination with ketoconazole, or alone, in selected cases of Cushing's disease
      or Nelson's syndrome.

PMID- 10971111
TI  - Growth hormone-releasing hormone: past and present.
AB  - The discovery of hypothalamic hypophysiotropic factors confirmed the hypothesis
      of Green and Harris in the late 1940s. These hormones were isolated from their
      eutopic site of production (the hypothalamus) with the exception of growth
      hormone (GH)-releasing hormone (GHRH), which was isolated from an ectopic,
      tumoral site of production and found to be responsible for acromegaly. Following
      the isolation, characterization and synthesis of human GHRH, clinical studies
      were performed and are described below. Circulating levels of GHRH can be
      measured and provide the basis for the diagnosis of acromegaly related to the
      ectopic, tumoral production of GHRH. At present, GHRH is used as a test of GH
      secretion mainly as an adjunct to other agents which modify somatostatin status,
      or to GH-releasing peptides. Its therapeutic potential in children and the
      elderly is still under investigation. The role of GHRH in the pulsatile secretion
      of GH is described.

PMID- 10971112
TI  - Peptide-mediated immune responses in specific immunotherapy.
AB  - Conventional immunotherapy using whole allergen extracts has been shown to be an
      effective, disease-modifying treatment in carefully selected patients with
      allergic conjunctivo-rhinitis, asthma and bee and wasp venom hypersensitivity.
      However, this form of therapy is associated with the risk of systemic
      anaphylaxis, which, when severe, can be life threatening. A potentially
      significant reduction in the incidence of IgE-mediated events during
      immunotherapy may be achieved by the use of short peptides corresponding to T
      cell epitopes which, by virtue of their size, are incapable of cross-linking
      allergen-specific IgE bound to the surface of mast cells and basophils. Initial
      clinical studies have demonstrated degrees of efficacy which have, in some cases,
      been associated with adverse events occurring immediately or several hours after
      peptide administration. Preliminary data from studies employing shorter peptides
      (20 amino acids or less) suggest that improved efficacy may be achieved by using
      peptides of defined major histocompatibility complex-binding specificity
      administered in an incremental dose fashion comparable to conventional
      immunotherapy. This review will discuss the concept of peptide immunotherapy and
      the implications of recent studies.

PMID- 10971113
TI  - Occurrence of IgE antibody-recognizing N-linked glycan moiety of a soybean
      allergen, Gly m Bd 28K.
AB  - BACKGROUND: It has been reported that N-linked glycan moieties of glycoproteins
      function as IgE-reactive determinants. Gly m Bd 28K, a soybean allergen, was a
      glycoprotein with glycan moieties, which are supposed to be the Man(3)GlcNAc(2)
      backbone with the beta1-->2 xylose and alpha1-->3 fucose branches. The purpose of
      the present study was to examine the IgE-binding ability of the glycan moiety of
      Gly m Bd 28K in the binding reaction with patients' sera. METHODS: A peptide
      containing the glycan moiety was prepared from Gly m Bd 28K by digestion with
      lysyl endopeptidase. The binding site of the glycan moiety was determined by
      amino acid sequence analyses. The glycan moiety of the allergen was characterized
      using anti-horseradish peroxidase antibody (anti-HRP) recognizing the N-linked
      glycan moieties of glycoproteins. The binding of patients' IgE antibodies with
      their glycan moiety was examined by an immunostaining technique using the
      glycopeptide and its deglycosylated peptide derived from Gly m Bd 28K. RESULTS:
      The binding site of the glycan moiety in Gly m Bd 28K was shown to be its Asn20
      residue. Gly m Bd 28K did react with anti-HRP and the sera of soybean-sensitive
      patients, but the binding of IgE antibodies was inhibited by the preincubation
      with anti-HRP. Moreover, the glycopeptide also reacted with the sera of soybean
      sensitive patients, but its deglycosylated peptide did not react with any IgE
      antibodies of patients' sera. CONCLUSIONS: The specific IgE antibodies
      recognizing the N-linked glycan moieties of Gly m Bd 28K and other glycoproteins
      with homologous glycan moieties occur in the sera of soybean-sensitive patients.
      It was indicated that the N-linked glycan moieties such as that of Gly m Bd 28K
      may be one of the common IgE-reactive determinants distributed in various plant
      food proteins.

PMID- 10971115
TI  - Purification and partial characterization ofa 67-kD cross-react ive allergen from
      Imperata cylindrica pollen extract.
AB  - BACKGROUND: Grass pollens are known to induce type I allergic reactions in a
      large number of genetically predisposed individuals. Earlier studies have
      recognized Imperata cylindrica (Ic) pollen as an important source of aeroallergen
      which contained 7 IgE binding proteins in the MW range of 85-16 kD. OBJECTIVES:
      To isolate, purify and characterize a cross-reactive allergenic protein from Ic
      pollen extract for diagnosis and therapy of grass pollen allergy. METHODOLOGY: Ic
      pollen extract was fractionated using DEAE Sephadex A-50, Sephadex G-200 and Mono
      Q column. Allergenic activity of the fractions was checked by ELISA, skin tests,
      ELISA inhibition and immunoblot using sera of Ic-sensitive patients. A 67-kD
      protein was purified to homogeneity from Ic-VIII. The allergenic determinants of
      this protein were identified by SDS-PAGE and immunoblot after CNBr treatment.
      RESULTS: Among Ic fractions, Ic-VIII was highly potent by ELISA, skin tests and
      showed cross-reactivity with 4 other tropical grasses by immunoblot and ELISA
      inhibition. The subfraction Ic-VIIIe1 of Ic-VIII showed a band at 67 kD on SDS
      PAGE. On CNBr treatment, it gave 7 peptides, 3 of which were found to be
      allergenic. CONCLUSION: A 67-kD protein (Ic-VIIIe1) was isolated, purified to
      homogeneity and partially characterized. It showed cross-reactivity with tropical
      grasses tested and contained at least three allergenic determinants.

PMID- 10971114
TI  - Immunoblot analysis of IgE-binding antigens in paprika and tomato pollen.
AB  - BACKGROUND: The high incidence of occupational allergy in horticulture has only
      recently been recognized. We determined IgE against pollen and fruit from paprika
      and tomato plants in sera from 3 greenhouse workers and in 3 sera from food
      allergic patients. METHODS: Proteins in extracts of paprika and tomato pollen
      were incubated with patients' sera after covalent coupling of these proteins to
      agarose beads, or in immunoblots. RESULTS: IgE against paprika pollen, but no IgE
      against tomato pollen, was found in serum from 2 greenhouse workers who worked
      with paprika plants only. IgE binding of these 2 sera to agarose-bound paprika
      pollen extract could be inhibited by paprika pollen but not by tomato pollen
      extract. A greenhouse worker, who cultivated tomato plants, had IgE against both
      tomato and paprika pollen. IgE binding of this serum to agarose-bound paprika
      pollen extract could be inhibited by both paprika pollen and tomato pollen
      extract. Three food-allergic patients also had IgE against tomato and paprika
      pollen. IgE from 2 food-allergic patients recognized IgE-binding structures in
      paprika or tomato pollen that were also present in fruit from the corresponding
      plant. In contrast, no substantial cross-reactivity was observed between paprika
      pollen and fruit towards IgE from 3 greenhouse workers. In 4 of 5 sera that were
      positive in the paprika pollen immunoblot major IgE binding to allergens of about
      30 and 64 kD occurred. CONCLUSION: The presence of IgE against paprika or tomato
      pollen is not restricted to workers in horticulture; IgE against these pollen can
      also be present in food-allergic patients who have serum IgE against paprika
      and/or tomato fruit.

PMID- 10971116
TI  - Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1)
      allergen exposure among subjects living in Uberlandia, Brazil.
AB  - BACKGROUND: The role of mite allergen exposure in sensitization and development
      of asthma has been widely recognized. Previous studies have shown that
      Dermatophagoides pteronyssinus and Blomia tropicalis were the most prevalent
      house dust mites in Brazil, while D. farinae was rarely found. The aim of this
      study was to measure Der f 1 and Der p 1 allergen levels in Brazilian asthmatics'
      and controls' homes. METHODS: Sixty-four houses (32 asthmatic, 32 control) were
      visited for dust sampling from five sites. Der f 1 and Der p 1 levels were
      measured by two-site monoclonal-antibody-based ELISAs. RESULTS: The highest
      levels of Der f 1 and Der p 1 allergens were found in bedding samples from both
      asthmatics' and controls' homes. However, the geometric mean of Der f 1 levels
      (15.8 microgram/g of dust) was significantly higher than for Der p 1 (8.2
      microgram/g of dust) in these samples. In addition, allergen levels >/=10
      microgram/g of dust were found in 60-80% of the samples for Der f 1 and about 50%
      for Der p 1. CONCLUSIONS: These results indicate that high levels of Der f 1
      allergen are present in both asthmatics' and controls' homes, in contrast to
      previously reported data. Therefore, studies on exposure to mites should be
      performed in different cities, seasons and times, since the mite fauna might be
      subject to variations. Knowledge of the mite fauna will certainly improve the
      means of investigating the association between allergen exposure and
      sensitization, allowing to establish the inclusion of new mite extracts in
      inhalant skin test sets, and even to detect monosensitized patients with
      respiratory allergy.

PMID- 10971117
TI  - A method for measuring specific IgE in sera by direct ELISA without interference
      by IgG competition or IgG autoantibodies to IgE.
AB  - BACKGROUND: In measuring specific IgE levels in sera by direct ELISA, competition
      with coexisting IgG often impedes an exact IgE determination; additionally, IgG
      autoantibodies to IgE (IgG-IgE) in sera affect the assay. In this paper, we
      attempt to determine accurate specific IgE levels by selective removal of IgG
      with a protein G-immobilized gel (PG) and by acid treatment of the PG to
      compensate for the unintended removal of IgE, probably due to the PG binding IgG
      IgE. METHODS: IgG in sera was removed using PG at pH 7.0. Then, the PG was
      treated with citrate buffer at pH 3.0 for 5 min to liberate IgE from IgG-IgE
      complexes, after IgG-binding sites on the PG were saturated with bovine IgG,
      since PG came to bind IgE at acidic pHs. IgE levels were then measured by ELISA.
      RESULTS: The PG treatment of sera removed the effect of inhibitory competition by
      coexisting IgG, especially at higher concentrations of sera, to improve specific
      IgE detection by direct ELISA. However, PG treatment alone sometimes reduced IgE
      levels (39% of sera tested), even though PG does not bind IgE at pH 7.0, which
      indicated the presence of IgG-IgE complexes. The reduction in IgE returned almost
      to their original levels in the sera by acid treatment of the PG. By combining
      the PG treatment with acid treatment, specific IgE measurement in sera was
      improved significantly (p < 0.01, Wilcoxon signed rank test). CONCLUSION:
      Measurement of specific IgE in sera by direct ELISA was improved by using the PG
      and acid treatment technique.

PMID- 10971118
TI  - Involvement of eosinophils in the early-phase allergic reaction in a guinea pig
      rhinitis model.
AB  - BACKGROUND: Eosinophils are found in the nasal lavage fluid (NLF) and nasal
      biopsies of patients with allergic rhinitis after a nasal antigen challenge, and
      associated not only with a late-phase allergic reaction (LPR) but also an early
      phase allergic reaction (EPR). Numerous studies have been carried out to clarify
      the participation of eosinophils in LPR or airway hyperresponsiveness. However,
      there has been no published report describing in detail the role of eosinophils
      during EPR. To better understand the involvement of eosinophils in EPR, we
      studied the effects of repeated antigen challenges on nasal airway responsiveness
      and eosinophilic inflammation in EPR using a guinea pig rhinitis model. METHODS:
      Nasal airway responsiveness was measured as the nasal airway resistance (NAR)
      after nasal antigen provocation. Eosinophilic inflammation during EPR was
      assessed by nasal lavage and histopathological examination using two groups of
      animals: those in group 1 were subjected to a sensitization pretreatment only,
      and those in group 2 were subjected to a pretreatment of sensitization followed
      by repeated nasal challenges. RESULTS: Repeated antigen challenges induced nasal
      hyperresponsiveness as indicated by a decrease in the antigen provocation dose
      and a significant increase in NAR. Furthermore, significant increases in
      eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in
      NLF during EPR were observed following antigen provocation in group 2. There were
      significant correlations between the levels of these parameters, and albumin was
      the most prevalent of the proteins in NLF. Histopathological examination showed
      that the degree of eosinophil infiltration into the lamina propria of the nasal
      mucosa of the animals in group 2 was significantly and apparently higher than in
      group 1. Particularly, epithelial disruption and mucosal edema were significantly
      elevated after antigen provocation in group 2. CONCLUSIONS: These results suggest
      that chronic eosinophil accumulation is induced by repeated antigen challenges in
      the nasal tissue, and that once antigen provocation occurs, eosinophils in the
      tissue are activated and responsible for the amplification of EPR such as
      vascular permeability and mucosal edema.

PMID- 10971119
TI  - Autoantibody reactivity in a case of Schnitzler's syndrome: evidence for a Th1
      like response and detection of IgG2 anti-FcepsilonRIalpha antibodies.
AB  - Schnitzler's syndrome is a rare disease characterized by chronic urticaria,
      monoclonal IgM, and clinical and laboratory signs of inflammation. In a subset of
      patients, the urticarial lesions cause pruritus. However, the pathophysiology of
      the disease and the biochemical basis of urticaria are not known. We describe a
      female patient with Schnitzler's syndrome suffering from chronic urticaria
      associated with pruritus. The patient's serum was found to contain IgG antibodies
      recognizing cellular components of the microvasculature. In particular, IgG3
      antibodies directed against proteins (14-100 kD) expressed in cultured dermal
      microvascular endothelial cells and mast cells, were found by immunoblotting.
      Moreover, IgG2 antibodies specific for the alpha-chain of the FcepsilonRI were
      detectable. However, the autoantibodies did not mediate histamine release in mast
      cells or basophils. In patients with IgM paraproteinemia who did not have
      Schnitzler's syndrome, antibodies against endothelial/mast cells or FcepsilonRI
      were not detectable. In summary, we describe subclass-specific IgG reactivity
      against microvascular endothelial cells and mast cells indicating Th1
      autoimmunity in a patient with Schnitzler's syndrome. Whether such autoantibodies
      are recurrently produced in patients with Schnitzler's syndrome and play a role
      in the pathophysiology of the disease remains to be determined.

PMID- 10971120
TI  - Induction of high levels of antibodies recognizing the neutralizing epitope
      ELDKWA and the D- or K-position-mutated epitopes by candidate epitope vaccines
      against HIV-1.
AB  - Monoclonal antibody 2F5 recognizing the ELDKWA epitope on HIV-1 gp41 has a
      significant neutralization potency against 90% of the investigated viruses of
      African, Asian, American, and European strains, but the antibody responses to the
      epitope 2F5 in HIV-1-infected individuals were very low. We attempted to induce
      high levels of epitope-specific antibodies to ELDKWA and its three mutated
      epitopes by candidate epitope vaccines. The four candidate epitope vaccines all
      induced strong antibody responses at dilutions from about 1:6,400 to 1:25,600. We
      tested the cross-reactions between these antisera and four epitope peptides. The
      ELDKWA-specific antisera showed strong cross-reactivity with three neutralizing
      resistant mutated epitopes which contain changes in the D or K positions of the
      epitope sequence. Virus variants containing these changes could escape
      neutralization by monoclonal antibody 2F5. In immunoblotting analysis, the
      ELDKWA, ELDEWA, and ELEKWA epitope specific antibodies all recognized rsgp41
      which confirms that the antibodies against both mutated epitopes, ELDEWA and
      ELEKWA, could cross-react with the native epitope on rsgp41. Although it is not
      clear whether the polyclonal antibodies induced by the ELDKWA epitope vaccine
      could neutralize the mutated viruses containing these mutated epitopes, it is
      conceivable that epitope vaccines based on mutated epitopes could induce strong
      antibody responses with predefined epitope specificity to neutralize mutated
      viruse containing the mutated epitope. An epitope vaccine, using different
      epitopes including mutated epitopes, could provide a new concept for developing a
      new vaccine against HIV-1.

PMID- 10971121
TI  - Reduced frequencies of peripheral interferon-gamma-producing CD4+ and CD4- cells
      during acute Kawasaki disease.
AB  - BACKGROUND: This study was performed to analyze the frequencies of peripheral
      interferon (IFN)-gamma-producing cells at the single-cell level and to determine
      concentrations of circulating IFN-gamma in the acute and subacute phases of
      Kawasaki disease (KD). METHODS: Ten patients with KD were studied and seven
      healthy children were selected as control subjects. Using immunofluorescent
      detection of intracellular IFN-gamma in CD4-positive and CD4-negative cells, the
      frequencies of IFN-gamma-producing cells in peripheral blood mononuclear cells
      were studied. Circulating IFN-gamma levels were measured by enzyme-linked
      immunosorbent assay. RESULTS: The frequencies of peripheral blood CD4+ and CD4-
      IFN-gamma-producing cells in acute-phase KD patients were significantly lower
      than in subacute-phase KD patients and control children (p < 0.05). CD4- cells,
      thought to be mainly composed of CD8+ cells, appeared to be more responsible for
      the reduced frequencies of total IFN-gamma-producing cells than CD4+ cells. There
      were, however, no differences in the frequencies of IFN-gamma-producing cells
      between KD patients in the subacute phase and control children. In contrast,
      serum IFN-gamma levels were higher in KD patients in the acute phase than in the
      subacute phase (p < 0.05). CONCLUSIONS: The above results show increased levels
      of circulating IFN-gamma and decreased emergence of peripheral IFN-gamma
      producing cells in acute KD patients, suggesting transient infiltration of
      activated IFN-gamma-producing cells into the inflammatory sites during acute KD.
      These findings also support the hypothesis that IFN-gamma plays an important role
      in the pathogenesis of KD-related vasculitis.

PMID- 10971122
TI  - Synthesis of factor D by normal human hepatocytes.
AB  - BACKGROUND: Unlike most complement proteins, complement factor D is believed to
      be synthesized not by the liver but exclusively by adipose tissue. METHOD:
      Culture supernatants obtained from primary culture of normal human hepatocytes
      were assayed for factor D by ELISA and analyzed by Western blotting. RESULTS:
      When normal hepatocytes were cultured in protein-free medium without addition of
      any stimulator for 5 days, factor D was detected in the supernatants at levels as
      high as 331.07 +/- 41.38 microgram/10(6) cells. Addition of TNF-alpha, IFN-gamma,
      IL-1beta or LPS to the medium did not result in any distinct effect on the
      amounts of secreted factor D. Reversible inhibition of factor D secretion by
      these cells was observed when cultured in the presence of cycloheximide. By
      immunoblot analysis, secreted factor D exhibited double bands, one with a
      molecular weight similar to factor D in normal human serum and the other with a
      slightly larger molecular weight. CONCLUSION: Normal human hepatocytes synthesize
      factor D constitutively. The liver may be a major source of plasma factor D.

PMID- 10971123
TI  - High frequency of HCV infection in individuals with isolated antibody to
      hepatitis B core antigen.
AB  - Although isolated antibody to hepatitis B core antigen (anti-HBc) is frequently
      nonspecific or may be the only serological marker of past self-limiting hepatitis
      B, where antibodies against the surface antigen have disappeared, isolated anti
      HBc seropositivity is frequently associated with chronic hepatitis B in HIV- and
      HCV-infected individuals. Of 5,520 samples that tested positive for anti-HBc (IMx
      and AxSYM CORE, Abbott, Delkenheim, Germany) at the Institute of Virology,
      University Clinic Frankfurt during the time interval from January 1994 to
      February 1996, 643 (11.6%) were isolated anti-HBc-reactive in the IMx and AxSYM
      CORE assays (inhibition values >90%). There was a statistically significant
      association between isolated anti-HBc seropositivity and HCV and HIV/HCV
      coinfection (p < 0.05). A total of 190 samples were available for further
      testing. Six (3.2%) of 190 isolated anti-HBc-positive samples were considered
      false-positive since they were only positive in the AxSYM or IMx CORE assay and a
      linear decrease of the measured signal could not be observed in dilution series.
      Of 184 serum samples tested with nested PCR using primers of the S genome region,
      only 6 (3.3%) were HBV DNA-positive. Anti-HBc-IgM antibody could be detected in 3
      (1.6 %) of the tested samples using the IMx CORE-M. With the more sensitive VIDAS
      HBc IgM specific IgM antibody was detected in 15 (8.5%) of 177 samples at
      concentrations ranging from 10 to >200 Paul Ehrlich Institute U/ml. HIV or HCV
      coinfection was present in 28.1% and 37.5% of isolated anti-HBc-positive
      individuals, respectively. We conclude from our observations that only a limited
      proportion of anti-HBc-isolated individuals are potentially infectious, however
      anti-HBc-IgM which is detectable in any form of liver disease associated with HBV
      infection was present in more than 8% of the individuals. Of isolated anti-HBc
      positive sera 37% were positive for anti-HCV, suggesting that anti-HCV antibody
      testing should be performed in isolated anti-HBc-positive individuals.

PMID- 10971124
TI  - Human T lymphotropic virus I in Indonesia. Very low seroprevalence in the Jakarta
      area: antibodies in healthy blood donors and in various nonhematological
      diseases.
AB  - Human T lymphotropic virus I (HTLV-I) is a retrovirus associated with adult T
      cell leukemia/lymphoma, tropical spastic paraparesis and possibly with other
      diseases. The actual incidence of HTLV-I carriers in Asia and Africa is difficult
      to assess and values of 0-37% have been reported. A study in Papua New Guinea by
      Yamaguchi et al. [6]found 1.8% positive for antibody to HTLV-I and this area is
      geographically close to the eastern part of Indonesia. A collaborative study was
      carried out to establish the seroprevalence of HTLV-I in Indonesia using the same
      method as that used standardly by Yamaguchi et al. in Japan. In a first step we
      measured antibody to HTLV-I in 657 subjects including 127 healthy persons around
      Jakarta, 451 patients with various nonhematological diseases and 79 blood donors.
      The majority of these healthy persons and patients came from various tribes of
      west Indonesia. All samples were initially screened for HTLV-I by the
      aggutination test. Serum that caused agglutination of the final dilution of 1:16
      or more and/or showed positivity on ELISA was subjected to immunofluorescence
      testing using HTLV-I-producing MT-2 cells and Western blot analysis. Of the 657
      samples, only 1 sample (0.15%) was found to be positive by the agglutination
      test, but this sample was negative when subjected to WB. From these result we
      concluded that there was very low seroprevalence of HTLV-I in the Jakarta area,
      which was also reflected in the western part of Indonesia. Routine examination of
      blood donors for HTLV-I in this area may not be necessary.

PMID- 10971125
TI  - Persistent TT virus infection does not contribute to the development of non-A to 
      G hepatocellular carcinoma. A case-control study of 19 patients in Japan.
AB  - We tested the sera of patients with non-A, non-B, non-C, non-G (non-A to -G)
      hepatocellular carcinoma (HCC) for the presence of TT virus (TTV) DNA and
      clinicopathologically elucidated the relationship between TTV infection and
      hepatocarcinogenesis. The study cohort consisted of 19 patients with non-A to -G
      HCC. Detection of TTV DNA was performed by the nested polymerase chain reaction
      according to a previously published method. TTV DNA was detected in the sera of 9
      (47.4%) of the 19 patients with non-A to -G HCC. The clinical background factors
      and blood biochemical parameters of the TTV-DNA-positive and -negative HCC
      patients did not significantly differ. Three TTV-DNA-positive and 2 TTV-DNA
      negative patients underwent surgical resection of the HCC. The histological
      findings in the non-cancerous liver tissue of the TTV-DNA-positive and -negative
      patients did not significantly differ. In conclusion, TTV infection does not
      affect the features of non-A to -G HCC.

PMID- 10971126
TI  - Attachment and penetration properties of bovine herpesvirus 1 recombinants
      expressing pseudorabies virus glycoproteins gC and gB.
AB  - OBJECTIVE: Bovine herpesvirus 1 (BHV-1) has a relatively narrow host cell range
      in vitro and in vivo when compared to pseudorabies virus (PrV). The aim of this
      study was to elucidate whether homologous glycoproteins gC and gB from PrV can
      function in a heterologous BHV-1 background and whether the expression of these
      PrV glycoproteins influences the in vitro host cell specificity of BHV-1.
      METHODS: We constructed BHV-1 recombinants in which PrV gC and gB were expressed
      either individually or in combination, and examined their attachment and
      penetration properties in permissive Madin-Darby bovine kidney (MDBK),
      semipermissive hamster lung (HmLu-1) and nonpermissive murine embryo fibroblast
      (A31) cells. RESULTS: Two BHV-1 recombinants which expressed PrV gC exhibited
      remarkable competence in virus attachment to cells. The expression of PrV gB
      improved the virus attachment only a little but penetration, especially into HmLu
      1 and A31 cells, was enhanced. CONCLUSIONS: These results indicate that PrV gC
      and gB can function in a BHV-1 environment and facilitate virus attachment and
      penetration by BHV-1.

PMID- 10971127
TI  - The clinical features of chronic hepatitis C are not affected by the coexistence
      of hepatitis B virus DNA in patients negative for hepatitis B surface antigen.
AB  - Hepatitis B virus (HBV) DNA has been detected in the sera of hepatitis patients
      who are negative for hepatitis B surface antigen (HBsAg) by polymerase chain
      reaction (PCR). The purpose of the present study was to clarify the clinical
      characteristics of patients with chronic hepatitis C who are negative for serum
      HBsAg and positive for HBV DNA. The subjects included 49 patients with chronic
      hepatitis C who were negative for serum HBsAg and 119 blood donors who served as
      healthy controls. Serum samples were tested for the presence of HBV DNA by the
      nested PCR method. Serum HBV DNA was detected in 18 (37.7%) of the 49 chronic
      hepatitis C patients and in none (0%) of the 119 blood donors. Among the
      hepatitis C patients, HBV DNA was detected in 20.7% of those who were negative
      for all HBV-associated markers and in 57.1% of those who were positive for one or
      more HBV-associated marker. The HBV DNA-positive rate among those in each F stage
      did not significantly differ. The liver function parameters of the HBV DNA
      positive and the HBV DNA-negative chronic hepatitis C patients did not
      significantly differ. These results suggest that hepatitis C virus is frequently
      coinfected with serum HBsAg-negative HBV, and that the incidence of HBV infection
      in blood donors is low. However, it is considered that HBsAg-negative HBV
      infection does not modify the blood biochemical features of chronic hepatitis C.

PMID- 10971128
TI  - Sequence analysis and variation of EBNA-1 in Epstein-Barr virus-related
      herpesvirus of cynomolgus monkey.
AB  - OBJECTIVES: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is an
      important protein for immortalization and tumorigenesis of infected cells. EBNA-1
      gene variants may play a role in tumorigenesis. We determined the nucleotide and
      amino acid (aa) sequences of EBNA-1 in EBV-related herpesviruses from cynomolgus
      monkeys (cynomolgus-EBV) which induced malignant lymphomas in its natural host
      and in rabbits, and compared them with sequences of EBV and other
      lymphocryptoviruses (LCVs). METHODS: Polymerase chain reaction and direct
      sequencing methods were performed using extracted DNA from cynomolgus-EBV
      infected cell lines. RESULTS: The amino acid sequences of cynomolgus-EBV EBNA-1
      from two cell lines (Si-IIA: 588 aa; Ts-B6: 619 aa) which are antigenically cross
      reactive to human EBV EBNA-1 showed homology with human EBV (Si-IIA: 53%; Ts-B6:
      58%) and other LCVs from baboons (54 and 52%) and rhesus monkeys (60 and 58%),
      especially in the C-terminal unique domain. Homology of the EBNA-1 sequence
      between Si-IIA and Ts-B6 was 92%. The sequence difference between EBV and the
      related LCVs was manifested mainly in the length of the internal repeat 3
      corresponding region, which contains serine in the glycine/alanine repeat region
      of nonhuman LCVs. CONCLUSION: Sequence variation of cynomolgus-EBV EBNA-1 from
      different cell lines was observed. However, their sequences show a relatively
      high homology with human EBV and share the common features of EBNA-1 of EBV and
      other LCVs.

PMID- 10971129
TI  - Efficient diagnosis of dengue infections using patients' peripheral blood
      leukocytes and serum/plasma.
AB  - OBJECTIVE: Dengue fever has been one of the most important health problems in
      Taiwan since a large outbreak during 1987 and 1988. It is critically necessary to
      have a diagnostic approach that can detect early infections in an outbreak or
      even find infections existing in silent transmission of the disease. METHODS: To
      develop an efficient diagnostic protocol, 105 plasma/serum and 35 peripheral
      blood leukocyte (PBL) specimens from the 1994 outbreak in southern Taiwan were
      collected for assessment by various diagnostic techniques in this study. RESULTS:
      In acute blood samples, dengue viruses were isolated from 19.4% (14/72) and 33.3%
      (14/42) of reported and confirmed cases, respectively. Viral RNA in serum/plasma
      was detected from 20.0% (12/60) of acute samples, which was significantly higher
      than that from convalescent samples (3/44; 6.8%). However, viral RNA in PBLs,
      detected by reverse transcription polymerase chain reaction (PBL-RT-PCR), could
      be observed in 73.2% (19/26) and 66.7% (6/9) of acute and convalescent samples,
      respectively. The persistence of dengue viruses in PBLs was also evidenced by the
      presence of viral antigens in 42.9% (4/7) of confirmed convalescent samples by
      the immunofluorescence antibody test. In addition, IgM antibodies were detected
      in 43.8% (46/105) of reported cases and 85.2% (46/54) of confirmed cases by the
      IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). CONCLUSIONS:
      Although IgM antibody detection achieved the highest detection rate among
      techniques assessed in this study, no individual test can actually reach full
      efficiency for early diagnosis of dengue infections. Here, we propose a protocol
      which applies MAC-ELISA and PBL-RT-PCR in sequence, by which 22 confirmed cases
      were definitely proved as dengue positive. High levels of both sensitivity and
      specificity were shown in this protocol.

PMID- 10971130
TI  - Propagation of human papillomavirus type 59 in the athymic mouse xenograft
      system.
AB  - Studies of human papillomavirus (HPV) infection are hampered by the lack of an
      adequate culture system. The athymic mouse xenograft system permits propagation
      of HPV, but only a few HPV types have been grown in this manner. To produce an
      oncogenic type for studies of HPV pathogenesis, a condylomata acuminata lesion
      from an immunosuppressed patient was used to prepare an infectious extract. The
      patient's lesion was shown by PCR analysis to contain abundant HPV 59 (an
      oncogenic type) and a lesser amount of HPV 11, a nononcogenic type. The extract
      was used to infect human foreskin tissue which was subsequently implanted into
      athymic mice. Characterization of implants recovered after 3-4 months of growth
      revealed the presence of HPV 59 exclusively. A second extract was prepared from
      one of these implants and used in an additional experiment to demonstrate the
      passage of HPV 59. Compared to the histopathologic changes induced by the
      prototypic nononcogenic HPV 11, infection with HPV 59 caused a higher degree of
      basal cell crowding, less acanthosis, minimal papillomatosis and less pronounced
      koilocytosis.

PMID- 10971131
TI  - Full or near full length nucleotide sequences of TT virus variants (Types SANBAN
      and YONBAN) and the TT virus-like mini virus.
AB  - TT virus (TTV) is a common virus and consists of many genotypes and variants. In
      addition, there exists a virus which both differs greatly from and retains a
      considerable resemblance to TTV, such as the TTV-like mini virus (TLMV) as we
      reported previously. Here we report the near full length genomic sequences of 4
      isolates of a new variant of TTV (designated YONBAN) along with the full length
      sequences of 2 isolates of the TTV-SANBAN lineage and 7 isolates of the TLMV
      species derived from human sera. The TTV-YONBAN sequences showed only about 50%
      identity at the nucleotide level to those of the prototype TTV (TA278) and to
      SANBAN, and even less to TLMV. Moreover, the ORF1 of YONBAN lacked the ATG
      initiation codon which is shared by all the TTV and TLMV isolates so far
      identified in humans; instead, YONBAN had a Kozak's rule-compatible ACG codon as
      the candidate initiation site for the ORF1 translation. Nevertheless, the overall
      genetic structure and the conserved amino acid motifs within the ORF1 and the
      ORF2 were well shared among the prototype TTV strains, the SANBAN and YONBAN
      variants, and TLMV. The most conserved nucleotide sequence was found in the
      noncoding region just upstream from the ORF2, allowing construction of a
      phylogenetic tree which implied that the TTV genotypes and variants, the TLMV,
      and chicken anemia virus could be coclassified under a superfamily for which we
      proposed the name of 'Paracircoviridae' in our previous report.

PMID- 10971132
TI  - Identification of a single nucleotide polymorphism in the MxA gene promoter (G/T
      at nt -88) correlated with the response of hepatitis C patients to interferon.
AB  - The interferon (IFN)-inducible MxA protein is known to play an important role in
      the host defense against certain viruses. We aimed to see if any genetic
      polymorphism in the promoter region of the MxA gene is associated with the IFN
      responsiveness of hepatitis C virus (HCV)-infected patients. Initially we
      sequenced the promoter region of the MxA gene in 12 subjects and found a
      polymorphic site. We then constructed a specific PCR-RFLP system for this site
      and subjected 63 samples from chronic hepatitis C patients who were nonresponders
      (NR) to IFN therapy to it, 52 with sustained response (SR), and 42 healthy
      controls. Subjects were all Japanese, and unrelated. A single nucleotide
      polymorphism (SNP) was identified in the MxA promoter region: G/T alleles at nt
      position -88. Interestingly, this SNP was involved in a genetic element highly
      homologous to the IFN-stimulated response element consensus sequence, and the G
      to-T change there makes this homology a little greater. The rate of G.G
      homozygosity was 31% in the SR patients, significantly lower than in the NR
      patients (62%, p = 0.0009), while that of healthy controls was between the two
      groups (48%). Differences in HCV genotypes did not influence this result. Based
      on these findings, we propose that the SNP of the MxA promoter at nt -88
      identified in this study affects the expression of MxA protein, and may thus be
      associated with the response of HCV patients to IFN.

PMID- 10971133
TI  - Preventive and therapeutic vaccines for human papillomavirus-associated cervical
      cancers.
AB  - 'High risk' genotypes of the human papillomavirus (HPV), particularly HPV type
      16, are the primary etiologic agent of cervical cancer. Thus, HPV-associated
      cervical malignancies might be prevented or treated by induction of the
      appropriate virus-specific immune responses in patients. Sexual transmission of
      HPV may be prevented by the generation of neutralizing antibodies that are
      specific for the virus capsid. In ongoing clinical trials, HPV virus-like
      particles (VLPs) show great promise as prophylactic HPV vaccines. Since the
      capsid proteins are not expressed at detectable levels by basal keratinocytes,
      therapeutic vaccines generally target other nonstructural viral antigens. Two HPV
      oncogenic proteins, E6 and E7, are important in the induction and maintenance of
      cellular transformation and are coexpressed in the majority of HPV-containing
      carcinomas. Therefore, therapeutic vaccines targeting these proteins may provide
      an opportunity to control HPV-associated malignancies. Various candidate
      therapeutic HPV vaccines are currently being tested whereby E6 and/or E7 are
      administered in live vectors, in peptides or protein, in nucleic acid form, as
      components of chimeric VLPs, or in cell-based vaccines. Encouraging results from
      experimental vaccination systems in animal models have led to several
      prophylactic and therapeutic vaccine clinical trials. Should they fulfill their
      promise, these vaccines may prevent HPV infection or control its potentially life
      threatening consequences in humans.

PMID- 10971134
TI  - Protein oxidation and turnover.
AB  - All biomacromolecules are faced with oxidative stress. Oxidation of a protein
      molecule always induces inactivation of the molecule and introduces a tag to that
      molecule. These modified protein molecules are prone to degradation in vivo by
      the proteasome system. Coupling of protein modification and degradation of
      chemically modified proteins is one of the normal protein turnover pathways in
      vivo. We call this a 'chemical apoptosis' process, which is one of the early
      manifestations of programmed cell death. Impairment of the proteasome system
      leads to accumulation of modified nonfunctional proteins or 'aged proteins' that
      might cause various clinical syndromes including cataractogenesis, premature
      aging, neurological degeneration and rheumatoid disease. The metal-catalyzed
      oxidation of biomacromolecules provides an excellent artificial aging system in
      vitro. The system is very useful in the characterization of structure and
      function relationships of proteins (enzymes), especially in those containing
      metal binding domain(s), because the oxidation is always followed by an affinity
      cleavage at the metal binding site(s) that allows easy identification and further
      characterization.

PMID- 10971135
TI  - Oscillatory zones and their role in normal and abnormal sheep Purkinje fiber
      automaticity.
AB  - The mechanisms by which low [K(+)](o) induces spontaneous activity was studied in
      sheep Purkinje fibers. Purkinje strands were superfused in vitro and membrane
      potentials were recorded by means of a microelectrode technique. The results show
      that low [K(+)](o) increases the slope and amplitude of early diastolic
      depolarization, sharpens the transition between early and late diastolic
      depolarizations, induces an after-potential and large pre-potentials through a
      negative shift of an oscillatory zone. Pre-potentials occur progressively sooner
      during diastole and merge with the after-potential to induce uninterrupted
      spontaneous discharge. During recovery, when the rate slows, after- and pre
      potentials separate once more, the slower discharge decreasing the after
      potentials but not the pre-potentials. Low [K(+)](o) has little effect on the
      plateau, but markedly slows phase 3 repolarization and may altogether prevent it.
      At depolarized levels, voltage oscillations, slow responses, sinusoidal
      fluctuations or quiescence may be present depending on voltage. During the
      recovery, a train of either sub-threshold oscillations or spontaneous action
      potentials appear towards the end of phase 3 repolarization. The cessation of the
      action potentials unmasks large sub-threshold oscillations, that occur in the
      oscillatory zone. Drive, high [Ca(2+)](o) and norepinephrine increase slope and
      amplitude of early diastolic depolarization as low [K(+)](o) does. In low
      [K(+)](o), Cs(+) prevents spontaneous discharge at polarized levels, but not the
      decrease in resting potential nor the onset of slow responses at depolarized
      levels. Cs(+) blocks the train of oscillations and of action potentials occurring
      during recovery. We conclude that low [K(+)](o) steepens early diastolic
      depolarization and increases its amplitude through an after-potential that
      results from an increased Ca(2+) load; allows the attainment of the threshold
      through Cs(+)-sensitive voltage oscillations which develop when the oscillatory
      zone is entered either by diastolic depolarization or by phase 3 repolarization;
      and causes voltage oscillations also at depolarized levels, but through a Cs(+)
      insensitive different mechanism.

PMID- 10971136
TI  - Role of protein kinase C in mediating alpha-1-adrenoceptor-induced negative
      inotropic response in rat ventricles.
AB  - The aim of this study was to determine the effect of protein kinase C (PKC)
      activation on intracellular Ca(2+) transient and its relation to alpha(1)
      adrenoceptor (alpha(1)-AR)-stimulated negative inotropic response in rat
      ventricles. The electromechanical responses to phenylephrine (PE) in rat
      ventricular muscles were concomitantly examined using the conventional
      microelectrode method. The responses of intracellular Ca(2+) transient and cell
      contractions to PE in the absence of certain pharmacological interventions were
      ascertained in fura-2-loaded myocytes. The influence of PE on L-type Ca(2+)
      current (I(Ca,L)) was also examined using a voltage clamp in a whole-cell
      configuration. PE did not alter the action potential parameters during the
      negative inotropic phase. The negative inotropic effect (NIE) was inhibited by
      prazosin, chloroethylclonidine (CEC) and staurosporine, but was insensitive to
      pertussis toxin. Desensitization of PKC after prolonged pretreatment of rat
      ventricles with PDBu also abolished the NIE of PE. Caffeine modulated the NIE,
      but thapsigargin did not. The evoked intracellular Ca(2+) transient and cell
      contraction were initially decreased by PE, while I(Ca,L) was not altered.
      Prazosin and staurosporine significantly inhibited the responses. Our data
      indicated that alpha(1)AR-mediated NIE in rat ventricular muscles was due to the
      decrease of intracellular Ca(2+) transients by the modulation of PKC on Ca(2+)
      releasing channels signaling through a CEC-sensitive alpha(1)AR subtype.

PMID- 10971137
TI  - Basal and ethanol-induced cardiac contractile response in lean and obese Zucker
      rat hearts.
AB  - Obesity plays a pivotal role in metabolic and cardiovascular diseases. Certain
      types of obesity may be related to alcohol ingestion, which itself leads to
      impaired cardiac function. This study analyzed basal and ethanol-induced cardiac
      contractile response using left-ventricular papillary muscles and myocytes from
      lean and obese Zucker rats. Contractile properties analyzed include: peak tension
      development (PTD), peak shortening amplitude (PS), time to PTD/PS (TPT/TPS), time
      to 90% relaxation/relengthening (RT(90)/TR(90)) and maximal velocities of
      contraction/shortening and relaxation/relengthening (+/-VT and +/-dL/dt).
      Intracellular Ca(2+) transients were measured as fura-2 fluorescence intensity
      (DeltaFFI) changes and fluorescence decay time (FDT). In papillary muscles from
      obese rats, the baseline TPT and RT(90) were significantly prolonged accompanied
      with low to normal PTD and +/-VT compared to those in lean rats. Muscles from
      obese hearts also exhibited reduced responsiveness to postrest potentiation,
      increase in extracellular Ca(2+) concentration, and norepinephrine. By contrast,
      in isolated myocytes, obesity reduced PS associated with a significant prolonged
      TR(90), normal TPS and +/-dL/dt. Intracellular Ca(2+) recording revealed
      decreased resting Ca(2+) levels and prolonged FDT. Acute ethanol exposure (80-640
      mg/dl) caused comparable concentration-dependent inhibitions of PTD/PS and
      DeltaFFI, associated with reduced +/-VT in both groups. Collectively, these
      results suggest altered cardiac contractile function and unchanged ethanol
      induced depression in obesity.

PMID- 10971139
TI  - Modulatory effects of the human heat shock protein 70 on DNA vaccination.
AB  - DNA vaccination with the plasmid expressing Japanese encephalitis virus (JEV)
      nonstructural protein 1 (pJNS1) has been shown to induce effective immunity
      against JEV infection. To further increase the efficacy of pJNS1 DNA vaccination,
      we coinjected pJNS1 with a plasmid that expresses heat shock protein 70.1
      (pHSP70.1) into mice. We found that coinjection of pHSP70.1 enhanced both T cell
      proliferation and cytotoxic effects, but not the antibody response to JEV.
      Moreover, mice immunized with both pHSP70.1 and pJNS1 were resistant to lethal
      challenges of JEV, indicating that the protective immunity against JEV is not
      decreased, in spite of the low antibody titer via the immunization of pHSP70.1.
      Since DNA vaccination administered by pJNS1 did not elicit strong cellular
      immunity in our previous study, the administration of pHSP70.1 apparently could
      be used as an adjuvant to enhance cell-mediated immunity in this model system.
      Thus, coadministration of pHSP70.1 DNA with plasmid DNA encoding tumor- or virus
      specific antigens might be very useful in the treatment of cancers and other
      infectious diseases.

PMID- 10971138
TI  - Parabrachial nucleus induces suppression of baroreflex bradycardia by the release
      of glutamate in the rostral ventrolateral medulla of the rat.
AB  - The involvement of glutamatergic neurotransmission in the rostral ventrolateral
      medulla (RVLM) in the suppression of baroreflex bradycardia by the parabrachial
      nucleus (PBN) was investigated. Repeated electrical activation of the PBN
      increased the concentration of glutamate in the dialysate collected from the
      RVLM. The same stimulation also suppressed baroreflex bradycardia in response to
      transient hypertension evoked by phenylephrine (5 microg/kg, intravenously).
      Microinfusion of L-glutamate (10, 50 or 100 microM) via the microdialysis probe
      into the RVLM dose-dependently elicited a significant inhibition of baroreflex
      bradycardia that paralleled the concentration and time course of the PBN-elicited
      elevation in extracellular glutamate in the RVLM. The suppression of baroreflex
      bradycardia elicited by microinjection of L-glutamate (1 nmol) into the RVLM was
      appreciably reversed by coinjection of the NMDA receptor antagonist, dizocilpine
      (500 pmol), or the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3
      dione (50 pmol). These results suggest that an increase in the extracellular
      concentration of glutamate and activation of both NMDA and non-NMDA receptors in
      the RVLM may mediate the suppression of baroreflex bradycardia by activation of
      the PBN.

PMID- 10971141
TI  - Galanin-like peptide (GALP) mRNA expression is restricted to arcuate nucleus of
      hypothalamus in adult male rat brain.
AB  - Galanin-like peptide (GALP) is a novel 60-amino acid neuropeptide, isolated from
      porcine hypothalamus and subsequently identified in rats and humans, which has
      reported selectivity for the Gal-R2 galanin receptor [Ohtaki T et al: J Biol Chem
      1999; 274: 37041-37045]. In the current study, the regional and cellular
      distribution of GALP mRNA in rat brain has been investigated by in situ
      hybridization of [(35)S]-labelled oligonucleotide probes. In a thorough screening
      of adult male rat brain, GALP mRNA expression was detected only throughout the
      rostrocaudal extent of the arcuate nucleus (ARC) with the most abundant
      hybridization signal in the posterior, periventricular zones. GALP mRNA-positive
      neurons were mostly localized in the ventromedial division of the ARC, with many
      closely adjacent to the wall of the third ventricle. Smaller numbers of labelled
      neurons were also found in ventrolateral areas. The distribution of GALP mRNA was
      somewhat complementary to that for galanin (GAL) mRNA in the ARC, but contrasted
      with the broad distribution of this transcript throughout the hypothalamus. GAL
      mRNA was also distributed along the rostrocaudal extent of the ARC, but was most
      abundant in the anterior to middle levels and in ventrolateral regions.
      Interestingly, somatostatin mRNA expression appeared to overlap the distribution
      of GALP mRNA in posterior, ventromedial regions of the ARC. Thus, in adult rat
      brain GALP mRNA expression was restricted to a discrete subpopulation of neurons
      in the ARC, with a unique localization pattern unlike GAL or many other known
      peptide- and transmitter-containing cells in this region. GALP could, however, be
      co-expressed in sub-populations of other neuronal phenotypes (e.g. somatostatin
      neurons) or within cells that express Gal-R2 receptors. In view of the
      established anatomy and function of the ARC and the restricted localization of
      GALP mRNA, this novel peptide is likely to play a role in regulation of anterior
      pituitary hormone secretion, or in regulation of other hypothalamic peptide and
      transmitter systems.

PMID- 10971140
TI  - The action mode of the ribosome-inactivating protein alpha-sarcin.
AB  - Based on the tertiary structure of the ribosome-inactivating protein alpha
      sarcin, domains that are responsible for hydrolyzing ribosomes and naked RNA have
      been dissected. In this study, we found that the head-to-tail interaction between
      the first amino beta-strand and the last carboxyl beta-strand is not involved in
      catalyzing the hydrolysis of ribosomes or ribonucleic acids. Instead, a four
      strand pleated beta-sheet is indispensable for catalyzing both substrates,
      suggesting that alpha-sarcin and ribonuclease T1 (RNase T1) share a similar
      catalytic center. The integrity of an amino beta-hairpin and that of the loop L3
      in alpha-sarcin are crucial for recognizing and hydrolyzing ribosomes in vitro
      and in vivo. However, a mutant protein without the beta-hairpin structure, or
      with a disrupted loop L3, is still capable of digesting ribonucleic acids. The
      functional involvement of the beta-hairpin and the loop L3 in the sarcin
      stem/loop RNA of ribosomes is demonstrated by a docking model, suggesting that
      the two structures are in essence naturally designed to distinguish ribosome
      inactivating proteins from RNase T1 to inactivate ribosomes.

PMID- 10971142
TI  - Differential regulation of prolactin release and lactotrope proliferation during
      pregnancy, lactation and the estrous cycle.
AB  - The proestrous surge of prolactin (PRL) secretion and subsequent proliferation of
      lactotropes at estrus have been suggested to be induced by a common hypothalamic
      hormone. We investigated changes in lactotrope proliferation at other
      reproductive stages of female rats when PRL secretion was stimulated. To assess
      proliferative activity of lactotropes, incorporation of 5-bromo-2'-deoxyuridine
      (BrdU) into DNA was measured by double immunostaining for PRL and BrdU. BrdU
      labeling indices, determined by BrdU injections at 10.00 h, revealed low levels
      of proliferative activity of lactotropes at the reproductive stages including
      diestrus, days 6 and 13 of pregnancy, and day 6 of lactation while high levels
      were detected on estrus and the day of parturition. When BrdU-labeling indices
      were determined at 3-hour intervals through day 6 of pregnancy to find an
      increase in lactotrope proliferation which might occur at times other than 10.00
      h, proliferative activity of lactotropes remained at low levels with a slight
      increase in the afternoon. Such a diurnal change as observed in early pregnancy
      was not detected on day 13 of pregnancy. In contrast, short-interval
      determinations of BrdU-labeling indices during a period from day 20 of pregnancy
      to day 2 of lactation revealed a marked increase in proliferative activity on the
      day of parturition with a peak at 18.00 h, which was comparable to that observed
      at estrus. To investigate involvement of ovarian steroids in suppression of
      lactotrope proliferation as observed during early pregnancy and lactation,
      ovariectomized and pup-removed lactating rats were given one of treatment
      combinations of estradiol and suckling. In pup-removed lactating rats, estradiol
      treatment alone induced neither a PRL surge nor an increase in BrdU-labeling
      indices. Suckling stimuli, which were effective in increasing serum PRL
      concentrations irrespective of estradiol treatment, elicited a marked increase in
      BrdU-labeling indices in the presence of estradiol but not in its absence. These
      results suggest that proliferative activity of rat lactotropes does not
      necessarily correlate with PRL secretion during pregnancy and lactation. In
      contrast to PRL release, lactotrope proliferation requires both a
      hypophysiotropic stimulatory input from the hypothalamus and a sensitizing action
      of estradiol, an observation which may account for the fact that proliferation
      does not occur during pregnancy and lactation in spite of elevated PRL release.

PMID- 10971143
TI  - Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in
      F344 rats.
AB  - Female F344 rats treated chronically with diethylstilbestrol (DES) develop
      prolactin (PRL)-producing pituitary tumors. These tumors are larger in female
      than in male rats. To investigate gender differences in DES-induced pituitary
      tumor formation, we employed female and male rats and neonatally androgenized
      females, which received 100 microg of testosterone propionate (TP) after birth.
      At 3 months of age, all rats were deprived of their gonads and divided into
      control and DES-treated groups. Forty days after beginning treatment, control
      pituitary weight and serum PRL were similar in gonadectomized males (GDX),
      ovariectomized females (OVX) and androgenized-ovariectomized females (OVX + TP),
      but weight of DES-induced tumors was 2.5-fold higher and serum PRL 5.6-fold
      higher in OVX + DES than in GDX + DES or OXV + TP + DES (p<0.001). At the
      pituitary level, nuclear estrogen receptors (NE(2)R) amounted to >100 fmol/mg DNA
      in all rats receiving DES. However, NE(2)R were lower in OVX + DES (101.3+/-9.0
      fmol/mg DNA) than in GDX + DES (174.6 +/-16.8; p<0.05) and in OXV + DES + TP
      (150.3+/-27.7; p<0.05). A similar profile was found for cytosolic progestin
      receptors. Using electron microscopy (EM), hyperplasia/hypertrophy of lactotropes
      was found in all DES-stimulated pituitaries. However, tumors of OVX + DES rats
      were enriched in hyperstimulated typical lactotropes, i.e., cells with high rate
      of hormonal synthesis, processing and secretion. Instead, tumors from GDX + DES
      and OVX + TP + DES rats were a mixture of typical and atypical lactotropes, i.e.
      a cell subpopulation with refractory secretory response and a few gonadotropes.
      In agreement with these data, immunoreactive pituitary PRL was lower in OVX + DES
      than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity
      to DES, serum and tumor PRL, NE(2)R and progestin receptors between estrogenized
      female rats on one side and male and TP-androgenized females on the other, may by
      due in part to heterogeneity of cell populations. Our data further suggest that
      neonatal hypothalamic exposure to androgens, as in normal males or androgenized
      females with masculinization of hypothalamic centers, may condition the response
      to DES stimulation later in life.

PMID- 10971144
TI  - Maternal behavior stimulates c-fos activity within estrogen receptor alpha
      containing neurons in lactating rats.
AB  - Estradiol and other hormones are thought to be critical for the onset, but not
      maintenance, of maternal behavior in rats. Maternal behavior is instead
      maintained postpartum by tactile stimulation that dams receive during
      interactions with pups, and many neural sites implicated in the control of
      maternal behavior show elevated c-fos activity in response to this stimulation.
      Many of these sites also contain neurons that express the alpha subtype of the
      estrogen receptor (ERalpha). Because of possible interactions between tactile
      stimulation from pups, c-fos, and ERalpha in the lactating rat brain, we
      determined if populations of cells that show increased c-fos activity after
      maternal behavior in lactating rats also contain ERalpha. Dams were separated
      from their pups for 48 h beginning on day 5 postpartum. On day 7 postpartum,
      experimental dams were reunited with pups and mother-litter interactions were
      observed for 60 min. Control dams received no pup stimulation. Subjects were
      sacrificed 60 min later and brain sections were double immunolabeled for the Fos
      and ERalpha proteins. As expected, the number of ERalpha-immunoreactive (ERalpha
      ir) neurons did not differ between the two groups in the eight areas analyzed
      (lateral region of the lateral septum, posterodorsal medial amygdala, dorsal and
      ventral medial preoptic area, dorsal and ventral bed nucleus of the stria
      terminalis, lateral habenula, and ventrolateral caudal periaqueductal gray).
      Consistent with previous reports, maternal dams had 2- to 7-fold more Fos
      immunoreactive (Fos-ir) neurons in these sites compared with nonstimulated
      controls. Maternal dams had significantly more Fos-ir neurons that also contained
      ERalpha-ir in all sites, with the greatest increases in the ventral medial
      preoptic area, lateral habenula, and ventral bed nucleus of the stria terminalis.
      Between approximately 25 and 45% of the Fos-ir cells in the sites examined also
      expressed ERalpha. Thus, a substantial number of neurons that are genomically
      activated during maternal behavior contain ERalpha, raising the possibility that
      the postpartum display of maternal behavior can be influenced by ERalpha
      activity.

PMID- 10971145
TI  - Fine topography of brain areas activated by cold stress. A fos
      immunohistochemical study in rats.
AB  - Neuronal activity in response to acute cold exposure was mapped in the central
      nervous system of adult rats using Fos immunostaining. A single, 3-hour exposure
      to cold elicited strong Fos-like immunoreactivity in the medial preoptic nucleus
      that is known as the thermoregulatory center of the brain. By this technique,
      pontine and medullary thermosensitive areas have been first localized and
      outlined anatomically. The medullary thermosensitive neurons occupy well
      demarcated areas immediately ventral and dorsal to the spinal trigeminal nucleus,
      termed peritrigeminal and paratrigeminal nuclei, respectively. Cold-sensitive
      neurons were present in the dorsal part of the pontine reticular formation.
      Topographically, this area corresponds to the 'pontine thermoregulatory area',
      named on the basis of neurophysiological observations. In addition,
      thermosensitive neurons were found in the rostral thalamus and zona incerta.
      Several cell groups that showed strong Fos-like immunoreactivity in our previous
      pain-related stress experiments were also activated by cold exposure. The midline
      thalamic, hypothalamic dorsomedial, supramamillary and lateral parabrachial
      nuclei were targets of cold stress-induced noxious stimuli. Fos-positive neurons
      established specific topographical patterns in the paraventricular, arcuate,
      central amygdaloid nuclei, and the nucleus of the solitary tract. The possible
      involvement of central noradrenergic neurons in stress response to acute cold
      exposure was investigated by double immunostaining for tyrosine hydroxylase (TH)
      and Fos. None of the tyrosine hydroxylase positive neurons in the brain stem
      established Fos-like immunoreactivity, suggesting that the central noradrenergic
      system may have a minor, if any, role in cold-induced stress responses. Based on
      the topographical distribution of Fos-activated neurons, this study suggests that
      in addition to the hypothalamo-pituitary-adrenal axis, some other stress effector
      systems may play an important role in the maintenance of homeostasis during cold
      stress.

PMID- 10971146
TI  - Recovery of the hypothalamic-pituitary-adrenal response to stress. Effect of
      stress intensity, stress duration and previous stress exposure.
AB  - Pathological consequences of stress-induced activation of the hypothalamic
      pituitary-adrenal (HPA) axis may be related to the duration rather than to the
      intensity of HPA axis activation after exposure to the stressor. Consequently a
      fine analysis of post-stress events is of importance. The present experiments
      were designed to study the importance of three key factors in HPA recovery:
      intensity of the stressor (experiment 1), duration of exposure to the stressor
      (experiment 2) and previous experience of the animals with the situation
      (experiments 3 and 4). In experiment 1, analysis of both the response to the
      stressor and the poststress period showed that the stronger the stressor, the
      greater the area under the curve of HPA activation. In experiment 2, different
      groups of rats were exposed to different periods of immobilization (IMO) (20 min,
      1 h and 2 h) and sampled before, during and after exposure to IMO. The speed of
      recovery of plasma corticotropin (ACTH) levels was not related to the duration of
      exposure to the stressor. In experiments 3 and 4, the influence of previous
      experience with the stressor was studied in rats daily exposed to 20 min IMO or
      daily injected with hypertonic saline (HS) for 8 days and sampled on days 1, 2, 5
      and 8. Whereas a significant decline in plasma ACTH levels was not observed
      immediately after IMO until day 8, a single previous exposure to IMO was enough
      to enhance recovery 90 min after the end of exposure to IMO. Corticosterone
      levels were related to the number of previous experiences with the stressor only
      in the post-IMO period. In response to a novel stressor (forced swimming),
      chronic IMO rats showed a slightly impaired recovery as compared to stress-naive
      rats, suggesting that enhanced recovery of the HPA axis was specific for the
      homotypic stressor. After daily HS injections, a pattern similar to that after
      IMO was observed, the delayed, but not the early response of the HPA axis being
      reduced as a function of the number of previous experiences with the situation.
      Taken together, the present results suggest that the speed of recovery of the HPA
      axis after its activation by stressors is sensitive to the intensity of the
      stressors but not to their duration, and that adaptation to a repeated stressor
      is more apparent during the delayed HPA response.

PMID- 10971147
TI  - Disproportionate inhibition of feeding in A(y) mice by certain stressors: a
      cautionary note.
AB  - A study of the effects of insulin-induced hypoglycemia in the obese yellow agouti
      A(y) mouse was initiated to test the hypothesis that the central melanocortin
      pathways are required for a normal sympathetic response to hypoglycemia. An
      experimental protocol was performed in which young nonobese male mice were
      isolated and fasted beginning on day 1, then tested for glucose responses to
      insulin-induced hypoglycemia on day 2. Normal mice demonstrated the expected
      glucose rebound to hypoglycemia, exceeding baseline glucose levels by 2-3 times
      as a consequence of increased gluconeogenesis and glycogenolysis before returning
      to baseline levels. A(y) animals lacked the rebound, exhibiting instead a gradual
      restoration of baseline glucose levels. The results suggested a defective
      sympathetic response to hypoglycemia in the A(y) mouse. However, a more detailed
      analysis demonstrated that the lack of a hyperglycemic rebound was due to an
      acute inhibition of feeding specifically in the A(y) mouse, which resulted not
      from the hypoglycemia stressor, but rather from the stress of isolation. Handling
      and intraperitoneal administration of saline also specifically inhibited food
      intake in the A(y) but not the wild-type mouse, while restraint stress had an
      equivalent inhibitory effect on food intake on wild-type and A(y) mice. Since the
      A(y) mouse has defective hypothalamic melanocortin-4 receptor (MC4-R) signaling,
      these data imply that the central melanocortin pathway is necessary for
      regulating the effects of stress on feeding behavior. Furthermore, these data
      demonstrate the need for exercising extreme caution in designing experiments to
      analyze feeding behavior and metabolism in genetic or pharmacological models
      involving perturbation of the melanocortin system.

PMID- 10971148
TI  - Antiproteases and cells in the pathogenesis of beta(2)-microglobulin amyloidosis:
      role of alpha(2)-macroglobulin and macrophages.

PMID- 10971149
TI  - Smoking--a renal risk factor.
AB  - One of the most important tasks of clinical and experimental nephrology is to
      identify the risk factors of progression of renal failure. A major renal risk
      factor which has not been sufficiently acknowledged despite increasing evidence
      is cigarette smoking. Diabetologists were the first to recognize the adverse
      effects of smoking on the kidney: both in type 1 and in type 2 diabetes smoking
      (i) increases the risk of development of nephropathy and (ii) nearly doubles the
      rate of progression to end-stage renal failure. Until recently it was not known
      whether smoking also increases the risk to progress to end-stage renal failure in
      patients with primary renal disease. A retrospective multicenter European case
      control study showed that smoking is an independent risk factor for end-stage
      renal failure in patients with inflammatory and noninflammatory renal disease,
      i.e. IgA glomerulonephritis and polycystic kidney disease. The pathogenesis of
      the smoking-related renal damage is largely unknown. The intermittent increase in
      blood pressure during smoking seems to play a major role in causing renal damage,
      but further potential pathomechanisms are presumably also operative. Smoking as a
      renal risk factor is of great interest to diabetologists as well as
      nephrologists, but unfortunately so far this information has had little impact on
      patient management. The present article reviews the current knowledge about the
      renal risks of smoking and discusses the potential mechanisms of smoking-mediated
      renal injury.

PMID- 10971150
TI  - Urinary excretion of type IV collagen as a specific indicator of the progression
      of diabetic nephropathy.
AB  - AIMS AND METHODS: This study was carried out to clarify whether the urinary
      excretion of type IV collagen (u-IV collagen) detected by specific
      radioimmunoassay, can be used as an indicator for the progression of diabetic
      nephropathy. RESULTS: u-IV collagen was higher in diabetic subjects with
      microalbuminuria and overt proteinuria than those with normoalbuminuria, IgA
      nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, or
      control normal subjects. u-IV collagen was positively correlated with serum and
      urinary beta(2)-microglobulin and negatively with creatinine clearance only in
      diabetic patients, but not in patients with other glomerular diseases. The serum
      type IV collagen was not different between all the groups, and not correlated
      with its urinary excretion. In the advanced diabetic nephropathy, immunoreactive
      type IV collagen was detected in glomerular basement membrane (GBM), tubular
      basement membrane and Bowman's capsule much more than that in the normal kidney.
      CONCLUSION: These findings indicated increased production and degeneration of
      type IV collagen in diabetic nephropathy. It is suggested that augmented turnover
      of type IV collagen in GBM and tubular basement membrane results in increased
      concentrations of free u-IV collagen. Therefore, measurement of u-IV collagen may
      be a useful, specific indicator of the progression of diabetic nephropathy.

PMID- 10971151
TI  - Relationship between urinary albumin excretion and glomerular filtration rate in
      normotensive, nonproteinuric patients with type 2 diabetes mellitus.
AB  - BACKGROUND/AIM: In patients with type 2 diabetes mellitus, the relationship
      between glomerular filtration rate (GFR) and urinary albumin excretion remains an
      unresolved issue. In order to investigate the early renal function abnormalities,
      GFR and urinary albumin excretion were assessed, and their relationship was
      examined in normotensive patients with type 2 diabetes mellitus. METHODS: In a
      cross-sectional study of 85 nonhypertensive Japanese patients with type 2
      diabetes mellitus not showing overt proteinuria, the GFR was measured using
      (99m)Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients
      lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed
      microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as
      controls. RESULTS: The three groups were well matched with regard to gender, age,
      and body mass index. The GFR in microalbuminuric patients (134 +/- 23 ml/min/1.48
      m(2)) was significantly higher than in patients without microalbuminuria (108 +/-
      21 ml/min/1.48 m(2)) and in controls (109 +/- 18 ml/min/1.48 m(2); p < 0.0001).
      In type 2 diabetic patients, the GFR positively correlated with the
      logarithmically transformed urinary albumin excretion. Multiple regression
      analysis showed that the urinary albumin excretion was significantly and
      independently affected by GFR (beta = 0.548), duration of diabetes (beta =
      0.297), and systolic blood pressure (beta = 0.232; R(2) = 0.409; p < 0.0001).
      CONCLUSION: It is suggested that one of the mechanisms underlying increased
      urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is
      glomerular hyperfiltration.

PMID- 10971152
TI  - Diabetes mellitus worsens intrarenal hemodynamic abnormalities in nondialyzed
      patients with chronic renal failure.
AB  - Duplex Doppler sonography has been reported to be useful in examining the
      intrarenal hemodynamic abnormalities in various renal diseases. We investigated
      the impact of diabetes on intrarenal hemodynamics in patients with chronic renal
      failure (CRF). The resistive index and pulsatility index of the renal interlobar
      arteries were measured using duplex Doppler sonography in 90 CRF patients (serum
      creatinine >130 and <800 mmol/l, mean age 59 +/- 11 years). Forty-eight patients
      had type 2 diabetes and 42 did not. Twenty-nine age-matched, healthy subjects
      served as controls. Both resistive index and pulsatility index were greater in
      CRF patients than in the controls (p < 0.0001). No significant differences
      existed in age, sex, body mass index, total serum cholesterol, serum creatinine,
      estimated creatinine clearance, or mean blood pressure between the diabetic CRF
      and nondiabetic CRF groups. Resistive index and pulsatility index were
      significantly increased in the diabetic CRF patients compared to the nondiabetic
      CRF patients (p < 0.0001). Multiple regression analysis of all CRF patients
      revealed that resistive index was independently affected by the presence of type
      2 diabetes (F = 44.535), as well as decreased creatinine clearance (F = 18.157)
      and age (F = 15.160) (R(2) = 0.559, p < 0.0001). These results clearly
      demonstrated that intrarenal arterial resistance is significantly increased in
      CRF patients with type 2 diabetes compared to similar patients without diabetes.
      The impact of diabetes mellitus and advanced age on intrarenal hemodynamics may
      be due to intrarenal arteriosclerosis and interstitital lesions. Measurements of
      RI values in addition to conventional ultrasound imaging may add further
      information on such renal lesions.

PMID- 10971153
TI  - Association of angiotensin I converting enzyme gene polymorphism with reflux
      nephropathy in children.
AB  - Deletion polymorphism of angiotensin I converting enzyme (ACE) gene has been
      studied as a risk factor in various cardiovascular diseases and chronic
      nephropathies. Perturbation of local and systemic renin-angiotensin systems is
      one of the possible mechanisms of the progression of reflux nephropathy. In this
      study, the implication of ACE gene polymorphism in renal scarring and
      deterioration of renal function was analyzed in 66 children with vesicoureteral
      reflux. The genotype for the polymorphism was determined by PCR, and renal scar
      was identified by (99m)Tc-DMSA renal scan. The allelic frequency of the deletion
      polymorphism showed no significant difference either between patients with normal
      renal function and those with decreased renal function or between patients with
      renal scar and those without. We conclude that deletion polymorphism of ACE gene,
      as an independent variable, is not associated with reflux nephropathy in children
      with vesicoureteral reflux.

PMID- 10971154
TI  - Adequate seroresponse to influenza vaccination in dialysis patients.
AB  - BACKGROUND: Hemodialysis (HD) patients are immunocompromised, and they have been
      shown to react suboptimally to recommended vaccinations. Advances in dialysis
      therapy and other supportive measures may theoretically result in better immune
      system functions. Clinical evidence supporting this theory has, however, not been
      presented. With influenza vaccination response, we tried to address this
      question. METHODS: 42 HD and 15 continuous ambulatory peritoneal dialysis (CAPD)
      patients were vaccinated with a trivalent influenza vaccine, and the
      seroresponses at 5 weeks were measured. The results were compared with those of
      similarly vaccinated 20 nephrology outpatient clinic patients with varying
      degrees of renal insufficiency and those of 31 cardiac patients with normal renal
      function. RESULTS: The dialysis patients had higher prevaccination titers of
      hemagglutination-inhibiting (HI) antibodies to all three vaccine virus antigens
      than the other groups due to more frequent previous vaccinations. The dialysis
      patients exhibited lower antibody increases, but an almost comparable proportion
      of them reached a protective antibody level (HI titers > or =40) 5 weeks after
      vaccination [A/H3N2: 61% (cardiac patients), 35% (nephrology outpatient clinic
      patients), 67% (CAPD), and 36% (HD); A/H1N1: 71, 70, 80 and 60; B: 97, 90, 80,
      and 76%, respectively]. Among the HD group, all patients receiving parenteral
      calcitriol except 1 (83%), but only 50% of the other HD patients produced
      protective antibody titers at least to two out of three vaccine virus antigens.
      No other patient- or HD treatment-associated parameter was significantly related
      to the vaccination-induced antibody response. CONCLUSIONS: We conclude that
      influenza vaccination of dialysis patients according to current recommendations
      may be effective. Additionally, our results suggest that parenteral calcitriol
      treatment may augment the immune response of HD patients even in a clinically
      relevant way, an effect so far shown only in in vitro studies.

PMID- 10971155
TI  - A new lactate-based, plasticizer-free, neutral peritoneal dialysis fluid provided
      in a two-compartment system: effect on peripheral leukocyte function.
AB  - BACKGROUND: A new neutral peritoneal dialysis fluid (PDF; Balance) provided in a
      two-compartment bag (pH 7.4, no plasticizers, minimal glucose degradation
      products - GDP) was investigated in comparison with a neutral control (Hanks'
      balanced salt solution with gelatin 0.1%) and other PDFs with standard properties
      and plasticizers (Andy plus, pH 5.2, GDP), plasticizer free (stay safe, pH 5.2,
      GDP), and in addition plasticizer free after sterile filtration instead of heat
      sterilization (pH 5.2) regarding the function of peripheral blood leukocytes.
      METHODS: Blood was drawn from 12 volunteers, and blood monocytes (MN) and
      polymorphonuclear leukocytes (PMNL) were collected. The cells were incubated for
      30 min in control medium and the PDFs: glucose 1.5% (83 mmol/l) and 4.25% (238
      mmol/l). Respiratory burst of cells was evaluated by chemiluminescence and
      superoxide (SO) generation after stimulation with phorbol myristate acetate.
      RESULTS: In comparison with the control medium, incubation of MN in the two
      compartment PDF showed preservation of respiratory burst. In contrast, the
      incubation of MN in standard PDF and plasticizer-free PDF showed impaired
      functions. The same was found for PMNL. SO anion measurement in MN and PMNL after
      incubation in the new two-compartment PDF also showed preservation of cell
      function in comparison with the control medium. The incubation of PMNL in
      standard PDF and plasticizer-free PDF with a high glucose content showed
      depressed SO anion generation. CONCLUSIONS: These in vitro data demonstrate a
      better preservation of in vitro phagocyte function with adaptation of pH and
      reduction of glucose, GDP, and plasticizers in PDFs. The best results are
      achieved with the two-compartment, lactate-based neutral PDF.

PMID- 10971156
TI  - Potassium-sparing renal effects of trimethoprim and structural analogues.
AB  - BACKGROUND/AIMS: The antibiotic antagonists of folic acid trimethoprim,
      tetroxoprim, pyrimethamine and their antineoplastic analogue methotrexate have
      structural characteristics in common with the potassium-sparing diuretic
      triamterene. They may, therefore, share with triamterne potassium-sparing renal
      effects. METHODS: Clearance studies were performed on anesthetized male Sprague
      Dawley rats, and the drug effects on glomerular filtration rate and on urinary
      excretion of sodium, chloride, and potassium were studied. RESULTS: Trimethoprim
      and tetroxoprim, injected intravenously at doses ranging from 0.3 to 30 mg/kg,
      induced dose-dependent natriuretic and antikaliuretic renal effects, whereas
      pyrimethamine at doses ranging from 1 to 10 mg/kg and methotrexate at doses
      ranging from 10 to 50 mg/kg did not affect urinary sodium and potassium
      excretion. An antikaliuretic effect was also observed after application of the
      structurally related antiprotozoal compound pentamidine at doses ranging from 3
      to 10 mg/kg. In contrast to trimethoprim and tetroxoprim, the antikaliuresis was
      accompanied by a marked decrease of urinary sodium and chloride excretion at all
      of the doses tested. At 10 mg/kg, pentamidine induced a pronounced fall of the
      glomerular filtration rate (by 43.5%). CONCLUSIONS: Trimethoprim and tetroxoprim
      share with potassium-sparing diuretics natriuretic and antikaliuretic renal
      effects which may be caused by similar mechanisms in the distal nephron, whereas
      pyrimthamine and methotrexate do not. A depression of renal hemodynamics is an
      important factor involved in the antikaliuretic effect of pentamidine.

PMID- 10971157
TI  - Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant
      patient--cured by evacuation plus antibiotic therapy.
AB  - We present a 50-year-old female who experienced generalized convulsion 3 months
      after a successful cadaveric renal transplantation. The first cerebral CT scan
      indicated cerebral frontal infarction. Repeat CT some days later revealed
      progressive lesions, and a highly malignant tumor or abscess was suspected.
      Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI
      could not differentiate between these conditions, but a neutrophil granulocyte
      scan strongly suggested an infectious process. A stereotactic puncture of the
      frontal lobe was followed by temporary improvement. A severe progressive left
      sided hemiparalysis gave indication for a craniotomy with evacuation of the
      abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive,
      rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing
      the 16S rRNA. The patient was treated with meropenem plus rifampicin
      intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2
      months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose
      was doubled, and the dose of tacrolimus had to be tripled for maintenance of
      adequate trough concentrations. Five months following cessation of antibiotic
      treatment, the patient has regained normal strength and function in her left
      sided extremities and has a serum creatinine level of about 160 micromol/l (1.8
      mg/dl).

PMID- 10971158
TI  - Kidney, patient and new millennium nephrology.
AB  - The way nephrology develops in the new millennium is bound to be affected by
      changes in the nephrologist's clinical environment, as well as by the progress
      made in basic research which will need to find a clinical application. The
      nephrologist can expect to be more and more involved in renal substitution
      therapy, not just providing the treatment, but also managing the cost of the
      service. In the field of nephropathology, the highest expectations surround
      molecular biology and its application to both acquired and hereditary renal
      disease; the goal is to find an outlet for gene therapy in clinical practice.
      Artificial substitution therapy will focus chiefly on the project of 'intelligent
      dialysis', whereby biological and diagnostic components are combined according
      the specific needs of the individual patient. The ideal scenario for renal
      transplantation in the coming millennium would be one where donor supply matches
      the demand (xenotransplant?), where immunomodulation is perfected, and where
      diagnoses are based on precise biomolecular events observed in real time.

PMID- 10971159
TI  - Glomerulopathies associated with psoriasis: a report of three cases.

PMID- 10971160
TI  - Serum levels of macrophage migration inhibitory factor in various types of
      glomerulonephritis.

PMID- 10971161
TI  - Isolation of a coronavirus from urinary tract tumours of endemic Balkan
      nephropathy patients.

PMID- 10971162
TI  - Glomerular sclerotic area and tubulointerstitial changes. Prognostic significance
      in IgA nephropathy.

PMID- 10971163
TI  - Thrombocytopenia and anemia induced by niceritrol used for amelioration of
      hyperphosphatemia in a hemodialysis patient.

PMID- 10971164
TI  - Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver.
AB  - In advanced colorectal cancer, liver metastases are a major problem. In patients
      with liver metastases as the major site of disease hepatic arterial chemotherapy
      is a valid alternative to systemic treatment. In this review about hepatic
      arterial chemotherapy we will discuss the theoretical and practical aspects, the
      results and complications, the selection of patients for hepatic arterial
      chemotherapy, and its future developments.

PMID- 10971165
TI  - Splenic hemangiosarcoma. A case report.
AB  - Splenic hemangiosarcoma is a rare and aggressive tumor. Up to now, less than 150
      cases have been reported. We describe a patient with a rapide course. The
      diagnosis of hemangiosarcoma was based on immunohistochemical tests (factor-VIII
      associated antigen, CD31, CD34). Despite the improvement of diagnostic
      techniques, pathological examination and immunohistochemistry remain the only
      methods available for the diagnosis.

PMID- 10971166
TI  - Hypnosis in the treatment of anticipatory nausea and vomiting in patients
      receiving cancer chemotherapy.
AB  - AIMS AND BACKGROUND: In addition to nausea and vomiting following chemotherapy
      treatment, cancer patients can experience these side effects prior to a treatment
      session, the so-called anticipatory nausea and vomiting. As various psychological
      and neurophysiological aspects have been claimed to be implied in its
      etiopathogenesis, the present paper aims to shortly review the etiological,
      epidemiological and therapeutical assumptions on the topic, in particular the
      psychological-behavioral therapies. PATIENTS AND METHODS: The present study was
      carried out on 16 consecutive adult cancer patients affected by chemotherapy
      induced anticipatory nausea and vomiting who had received at least four treatment
      cycles. All of them were submitted to induction of relaxation followed by
      hypnosis. RESULTS: In all subjects anticipatory nausea and vomiting disappeared,
      and major responses to chemotherapy-induced emesis control were recorded in
      almost all patients. CONCLUSIONS: The experience highlights the potential value
      of hypnosis in the management of anticipatory nausea and vomiting; furthermore,
      the susceptibility to anticipatory nausea and vomiting is discussed under the
      psychoanalytic point of view.

PMID- 10971167
TI  - Combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support for the
      treatment of refractory or relapsed small-cell lung cancer.
AB  - OBJECTIVE: This study was conducted in refractory or relapsed small-cell lung
      cancer to determine activity and toxicity of the combination of cisplatin,
      ifosfamide, and irinotecan with rhG-CSF support. METHODS: Eighteen patients
      entered the trial. The median chemotherapy-free interval was 3.1 (range 1.0-14.5)
      months. Cisplatin (20 mg/m(2)) and ifosfamide (1.5 g/m(2)) were administered on
      days 1-4, and irinotecan (60 mg/m(2)) was administered on days 1, 8, and 15. In
      patients who experienced grade 4 hematological toxicity during the prior
      chemotherapy, the doses of cisplatin and irinotecan were reduced to 15 and 50
      mg/m(2), respectively. After 10 patients were entered, cisplatin and irinotecan
      were administered at doses of 15 and 50 mg/m(2), respectively. This regimen was
      repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50
      microgram/m(2) from days 50 to 18, except on the day of irinotecan treatment.
      RESULTS: All patients could be assessed for response and toxicity. There were 1
      complete and 16 partial responses, and an overall response rate of 94.4%. The
      median survival time of all patients was 339 days, and the 1-year survival rate
      was 47.5%. Hematological toxicities were significant. Grade 4 neutropenia and
      thrombocytopenia were observed in 61 and 33% of the patients, respectively.
      Diarrhea was mild and transient. There was no treatment-related death.
      CONCLUSION: The combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF
      support was highly active for the treatment of refractory or relapsed small-cell
      lung cancer.

PMID- 10971168
TI  - Risk-adapted chemotherapy of germ cell tumors with carboplatin, etoposide and
      bleomycin for low-risk and cisplatin, etoposide and ifosfamide for high-risk
      patients. A single-center study.
AB  - The prognosis of germ cell tumors treated with chemotherapy depends on the
      presence of nonseminomatous tumor, clinical parameters based on the tumor volume
      and site, as well as on the level of the tumor markers AFP, betaHCG and LDH. We
      report here on the results of a risk-adapted approach to the chemotherapy of germ
      cell tumors. Patients with low-risk tumors, defined as seminomatous disease
      and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung
      metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and
      betaHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m(2) i.v.
      day 1, etoposide 120 mg/m(2) i.v. days 1-3 and bleomycin 30 IU i.v. days 1, 8 and
      15 during the first 3 cycles (CEB(90)). Patients with high-risk disease were to
      receive 4 cycles of ifosfamide 1,500 mg/m(2) continuous infusion on days 1-4
      together with mesna 1,200 mg/m(2) days 1-5, cisplatin 20 mg/m(2) i.v. days 1-5
      and etoposide 100 mg/m(2) i.v. days 1-5 (VIP). Of the 60 patients treated with
      this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty
      five of 51 patiens treated with CEB(90) achieved complete remission (CR), 4
      achieved partial remission with marker negativity. Four patients with CR relapsed
      between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing
      CEB(90), 3 were treated successfully with surgery or further chemotherapy. With a
      median follow-up of 52 months, the estimated cause-specific 3-year survival is
      93% (95% confidence interval, CI, 80-98%). Seven of 9 high-risk patients treated
      with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had
      successful salvage therapy. With a medium follow-up of 63 months all patients
      remain alive and free of disease. Forty-six patients receiving CEB(90) were
      retrospectively classified to be in the good prognosis group according to the
      international germ cell consensus classification. Their estimated 3-year survival
      was 95% (CI 81-99%). We thus confirm that CEB(90) is a well-tolerated outpatient
      regimen with good results in good prognosis germ cell tumors. Bleomycin at a
      cumulative dose of 270 U might contribute substantially to the inferior effect of
      carboplatin as compared to cisplatin. However, in view of the results of
      randomized studies favoring cisplatin over carboplatin, it is not recommended to
      use this regimen outside a clinical trial.

PMID- 10971169
TI  - High frequency of metastatic Leydig cell testicular tumours.
AB  - 690 patients were treated for testicular tumour in the course of 18 years. The
      histology of 7 cases showed Leydig cell tumour. In 4 of the 7 cases, a metastatic
      process leading to death was observed. At the time of diagnosis, 5 patients were
      found to have low stage, whereas 2 of the patients had advanced lymphatic
      involvement. The hematogenous and lymphatic metastases proved to be resistant to
      chemotherapy. Contrary to the major part of the literature, retroperitoneal
      lymphadenectomy should be performed with this histological type for the exact
      pathological staging immediately following orchiectomy.

PMID- 10971170
TI  - Demonstration and diagnostic significance of pro-gastrin-releasing peptide in
      medullary thyroid carcinoma.
AB  - The expression of pro-gastrin-releasing peptide (proGRP) in medullary thyroid
      carcinoma (MTC) and other histological types of thyroid carcinoma was studied by
      an immunohistochemical technique, using polyclonal anti-proGRP antiserum.
      Immunoreactivity for proGRP was detected exclusively in MTC (n = 7); other
      histological types (n = 12) were all negative for proGRP. In addition, serum
      proGRP levels were elevated in patients with primary or recurrent MTC (n = 3),
      and they changed in parallel with serum calcitonin (CT), and carcinoembryonic
      antigen (CEA). These results show that proGRP, which is considered to be a
      specific marker for small-cell lung carcinoma, may be also a potential tumor
      marker for MTC, in addition to CT and CEA.

PMID- 10971171
TI  - Loss of heterozygosity on the short arm of chromosome 3 in renal cancer.
AB  - 3% of human cancers are renal cell carcinomas (RCC). The most common chromosome
      abnormality found in this tumor is loss of heterozygosity (LOH) on the short arm
      of chromosome 3, which suggests that there must be one or more tumor suppressor
      genes between 3p14 and 3p21 near the VHL gene which play a relevant role in renal
      cancer development. DNA from normal and tumor tissue from 40 patients at various
      stages of RCC was analyzed for LOH at three microsatellites mapped to 3p (3p14.1
      14.3; 3p21.2-21.3 and 3p25) by polymerase chain reaction). 42.5% of the tumors
      studied showed LOH on at least one locus. 30% showed LOH on only one locus; 5% on
      two loci and 7.5% on the three loci tested. LOH occurred only on nonpapillary
      tumors (p = 0.03). Interestingly, all the tumors with LOH on 3p21 were >/=25 mm
      (p = 0.04; relative risk 1.76, confidence interval: 1.3-2.3).

PMID- 10971172
TI  - Different expression of sialyl Tn antigen between polypoid and nonpolypoid growth
      types of advanced colorectal carcinoma.
AB  - Colorectal tumors can be classified based on their growth pattern into the
      polypoid growth type (PG-type) and nonpolypoid growth type (NPG-type). We
      examined sialyl Tn antigen expression in advanced colorectal carcinomas that were
      classified as PG-type and NPG-type cancers in order to ascertain whether or not
      such expression correlates with other biologically and clinically important
      differences. A total of 94 advanced colorectal carcinomas were examined for
      sialyl Tn antigen expression, which was immunohistochemically detected by the
      monoclonal antibody TKH2. Univariate and multivariate analyses using logistic
      regression models were performed. Forty carcinomas (42.6%) were negative and 54
      (57.5%) were positive for sialyl Tn antigen. Eighteen carcinomas (19.2%) were of
      PG type and 76 (80.8%) of NPG type. NPG-type cancers had a higher proportion of
      positive lymph node metastasis than PG-type cancers. Furthermore, sialyl Tn
      antigen was less often detected in NPG-type cancers (39 of 76; 51.3%) than in PG
      type cancers (15 of 18; 83.3%; p = 0.0167). Multivariate analysis showed that two
      variables, lymph node metastasis and sialyl Tn antigen expression in carcinoma,
      were independently related to tumor growth patterns, that is NPG type and PG
      type. These data suggest that the difference in sialyl Tn antigen expression
      between two kinds of tumor growth patterns of advanced colorectal carcinomas, PG
      type and NPG type, may reflect different biological behaviors during tumor
      progression.

PMID- 10971173
TI  - Gelatinase and inhibitor expression in soft tissue sarcomas: lack of correlation
      with distant metastasis.
AB  - The predominant mode of death for most patients with soft tissue sarcomas (STS)
      remains distant metastasis (DM). Current clinical predictors of DM are
      unreliable. Matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) correlate with biologic aggression in other tumors.
      The gene expression of the gelatinase, MMP-2 and MMP-9, and their respective
      inhibitors, TIMP-1 and TIMP-2, in STS was evaluated. Twelve fresh-frozen surgical
      specimens from patients with large (>5 cm) STS were analyzed. Six patients
      developed DM while 6 survived disease-free (DFS) at a minimum follow-up of 13
      months. Following mRNA isolation, reverse transcription-polymerase chain reaction
      was performed using primers for MMP-2, MMP-9, TIMP-1, and TIMP-2. Gene expression
      was determined by band densitometry. Ratios of MMP-9/TIMP-1 and MMP-2/ TIMP-2
      gene expression as well as MMP-2 protein activation ratio (active/inactive enzyme
      determined by gelatin zymography) were analyzed for correlation with DM and DFS.
      MMP-2 gene was expressed in 12 specimens, while MMP-9 was detectable in 9.
      Relative levels of MMP-2 and MMP-9, MMP2/TIMP-2 ratio, and MMP-9/TIMP-1 ratio
      were not significantly correlated with DM. Poor DFS was significantly correlated
      with high MMP-9/TIMP-1 ratio (p = 0.02). Active MMP-2 protein was detected in 12
      specimens, while active MMP-9 protein was detected in 2. No association was found
      between MMP-2 protein activation ratio and DM or DFS. While MMP-2 gene expression
      and protein activity occurred in these 12 specimens, gelatinase/inhibitor ratios
      (for both MMP-2 and MMP-9) appear to be poor predictors of DM in STS.

PMID- 10971174
TI  - High frequency of c-Met expression in gastric cancers producing alpha-
      fetoprotein.
AB  - Gastric cancers producing alpha-fetoprotein (AFP) have a poor prognosis and a
      high incidence of liver metastasis. Hepatocyte growth factor (HGF) and its
      receptor, c-Met, are known to induce mitosis and cell movement and to promote
      tumor progression. In the present study, c-Met and HGF expression in AFP
      producing gastric cancer was compared with those gastric cancers that do not
      produce AFP. Twenty-six patients with AFP-producing gastric cancers [AFP(+)] and
      26 patients stage-matched gastric cancers without AFP production [AFP(-)] were
      evaluated for c-Met and HGF expression and proliferating cell nuclear antigen
      labelling index using immunohistochemical analysis. A higher frequency of c-Met
      expression was observed in the AFP(+) group than in the AFP(-) group (p < 0.01).
      A higher expression of c-Met might be one explanation for the poorer prognosis of
      AFP-producing gastric cancers.

PMID- 10971175
TI  - Thymidylate synthase expression in epithelial ovarian cancer: relationship with
      thymidine phosphorylase expression and prognosis.
AB  - OBJECTIVE: Thymidylate synthase (TS) and thymidine phosphorylase (TP) are
      important enzymes involved in the de novo DNA synthesis and the salvage pathways
      for pyrimidine, respectively. Our purpose was to determine whether the gene
      expression of TS together with TP correlate with prognosis in epithelial ovarian
      cancer. METHODS: TS gene expression was analyzed by reverse transcription
      polymerase chain reaction in 20 samples from normal ovaries and 56 epithelial
      ovarian cancers previously studied regarding TP gene expression. TS and TP
      protein localization was examined by immunohistochemistry. RESULTS: TS gene
      expression was significantly higher in epithelial ovarian cancer than in normal
      ovaries (p = 0.001). In patients with epithelial ovarian cancer, TS gene
      expression did not correlate with patient age, clinical stage, histologic type,
      or histologic grade. High TS gene expression (> median) significantly correlated
      with a poorer survival (p = 0.02). No significant correlation between TS and TP
      gene expression and different immunoreactivity patterns were found. Combined
      analysis of TS and TP gene expression demonstrated that the relative risk of
      death for tumors with high TS and high TP expression was greater than that for
      either only high TS or high TP gene expression (p = 0.002). CONCLUSION: TS and TP
      combined may indicate a poor prognosis for patients with epithelial ovarian
      cancer.

PMID- 10971176
TI  - Paradoxical hormone responses of KPL-1 breast cancer cells in vivo: a significant
      role of angiogenesis in tumor growth.
AB  - In our previous study, the growth of KPL-1 human breast cancer cells was found to
      be stimulated by an antiestrogen, ICI 182, 780, and inhibited by 17 beta
      estradiol (E2) in vivo but not in vitro. To investigate the action mechanisms of
      these paradoxical responses, the effects of E2, ovariectomy (Ovex) and
      medroxyprogesterone acetate (MPA) on the growth, angiogenesis, apoptosis and
      expression of vascular endothelial growth factor (VEGF) were investigated. E2
      stimulated the growth of KPL-1 cells but MPA inhibited it in vitro. In contrast,
      E2 propionate inhibited the growth of KPL-1 cells in female nude mice but Ovex
      and MPA stimulated it. E2 propionate suppressed angiogenesis and increased
      apoptosis in KPL-1 tumors, but Ovex and MPA promoted angiogenesis and decreased
      apoptosis. Both mRNA expression and secretion of VEGF were stimulated by MPA in
      KPL-1 cells, but in E2-dependent ML-20 cells they were both inhibited by MPA. E2
      did not significantly influence VEGF expression in either cell line. These
      findings suggest that the abnormal modulation of VEGF expression by MPA and of
      the other angiogenic factor by E2 are responsible for the paradoxical growth
      responses of KPL-1 cells in vivo. To support this hypothesis, an antiangiogenic
      agent, TNP-470, was administered to mice bearing KPL-1 tumors. TNP-470
      significantly inhibited the growth of KPL-1 tumors stimulated by MPA.
      Antiangiogenic agents may be effective for the treatment of hormone-refractory
      breast cancer.

PMID- 10971177
TI  - An analysis of serum interleukin-6 levels to predict benefits of
      medroxyprogesterone acetate in advanced or recurrent breast cancer.
AB  - Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate
      (MPA) shows high response rates and the accessory effects of appetite
      stimulation, improvement in performance status (PS) and bone marrow protection.
      In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In
      this study, to clarify the significance of IL-6 in advanced or recurrent breast
      cancer, the relationship between the IL-6 level and clinical findings or effect
      of MPA was investigated. Sixty-five patients with recurrent or advanced breast
      cancer participated in a prospective study. The age of patients ranged from 28 to
      79 years with an average age of 51.3 years. IL-6 level was investigated in these
      patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent
      patients. Serum MPA level was measured by high-performance liquid chromatography
      and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases)
      and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level
      was significantly higher in recurrent cases, especially in those with visceral
      metastasis. Further, in patients for whom MPA therapy was effective, the IL-6
      level prior to the treatment was clearly low. The IL-6 level was significantly
      increased after 4 weeks. However, response to MPA was significantly higher and PS
      was improved in those cases demonstrating less increased IL-6 levels after 4
      weeks. In addition, the effect of MPA was significantly related to a higher serum
      concentration of MPA-positive ER, and longer disease-free interval, although
      there was no significant predictive factor for the clinical effect of MPA therapy
      in multivariate analysis. In conclusion, MPA therapy was effective in cases
      demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS
      was improved in those cases in which the degree of IL-6 increase was suppressed
      by MPA, and many such cases showed low IL-6 levels prior to MPA therapy.
      Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is
      suggested that MPA therapy might be useful in treating recurrent breast cancer,
      and its benefits might be mediated by IL-6.

PMID- 10971178
TI  - Total tumor cell elimination with minimum damage to normal tissues in
      musculoskeletal sarcomas following photodynamic therapy with acridine orange.
AB  - Acridine orange (AO) has unique biological actions enabling tumor visualization
      (fluorovisualization) and a strong cytocidal effect (photodynamic therapy: AO
      PDT) under illumination with blue light. Accordingly, in this study, we attempted
      to develop a new surgical technique for total tumor cell elimination using these
      photodynamic reactions with AO in a mouse osteosarcoma model. The results showed
      that local tumor recurrence was significantly inhibited (23%) in the group
      treated with curettage under fluorovisualization and AO-PDT, compared to that
      (80%) in the control group treated with curettage alone under ordinary light.
      Therefore, we concluded that the combination of curettage under
      fluorovisualization and AO-PDT may be useful for total tumor cell elimination
      with minimum damage to normal tissue in musculoskeletal sarcomas.

PMID- 10971179
TI  - Age-related nuclear cataract: a lens transport problem.
AB  - Age-related nuclear cataract is a major cause of blindness. It is characterised
      by opacification and colouration in the centre of the lens and is accompanied by
      extensive protein oxidation. The reason for the onset of nuclear cataract is not
      known, but it is proposed here that the underlying cause is the development, with
      age, of a barrier to the transport of metabolites within the lens. Such a barrier
      may result in an increase in the half-lives of reactive molecules, such as UV
      filters, thus promoting posttranslational modification of proteins in the nucleus
      and may also act to prevent an adequate flux of antioxidants from reaching the
      lens interior and, as a consequence, allow oxidation of nuclear components.
      Further, this oxidation may take place even if the lens outer cortex and
      epithelium remain perfectly functional.

PMID- 10971180
TI  - Analysis of UVA-related alterations upon aging of eye lens proteins by mini two
      dimensional polyacrylamide gel electrophoresis.
AB  - This study is a first approach to identify UVA-related alterations in situ of
      bovine eye lens proteins from the water-soluble and urea-soluble fractions upon
      aging. The fractions were obtained from irradiated long-term organ culture lenses
      and analyzed by mini two-dimensional gel electrophoresis. This micropreparative
      method followed by computer analysis allows high resolution and separation of
      microgram quantities of proteins and to detect spots which arose as a consequence
      of irradiation. To facilitate the analysis we first separated the water-soluble
      fraction into the major crystallin classes by gel filtration. Moreover, we
      immunoblotted the gel of the urea-soluble fraction with a specific antibody
      against the intermediate filament protein vimentin. Upon irradiation of young and
      adult lenses, alphaA-crystallin and vimentin showed obvious modifications. During
      aging the susceptibility to irradiation increased when vimentin started to
      degrade, whereas deamidation of alphaA-crystallin seems to occur.

PMID- 10971181
TI  - Effects of nilvadipine, nicardipine and verapamil on acute rise of aqueous flare
      induced by iris photocoagulation or intravenous lipopolysaccharides in pigmented
      rabbits.
AB  - The effects of nilvadipine, nicardipine and verapamil on the acute rise of
      aqueous flare induced by argon laser photocoagulation of the iris or by
      intravenous injection of lipopolysaccharides (LPS, 0.5 microg/kg) were
      investigated in pigmented rabbits. Nilvadipine, nicardipine and verapamil were
      injected intravenously. Aqueous flare was measured with a laser flare cell meter.
      Following photocoagulation, aqueous flare increased, reached its maximum at 45-75
      min and then decreased. After administration of LPS, aqueous flare increased,
      reached its maximum at 4 h and then returned to baseline levels at about 24 h.
      Flare reactions were inhibited by nilvadipine in a dose-dependent manner. The
      elevations were maximally inhibited by nilvadipine 30 min before photocoagulation
      or intravenous LPS. Two hundred micrograms per kilogram of nilvadipine inhibited
      81% of photocoagulation-induced flare elevation, while the same dose of
      nicardipine and verapamil inhibited 19 and 9% of the elevation, respectively. The
      same dose of nilvadipine inhibited 51% of LPS-induced flare elevation, while the
      same dose of nicardipine and verapamil inhibited 6 and 4% of the elevation,
      respectively. In conclusion, nilvadipine inhibited the experimental elevation of
      aqueous flare more effectively than did nicardipine and verapamil.

PMID- 10971182
TI  - Effects of topical clonidine on prostaglandin-E(2)-induced aqueous flare
      elevation in pigmented rabbits.
AB  - We evaluated the role of topical clonidine on experimental ocular inflammation.
      Transcorneal diffusion of prostaglandin (PG) E(2), 7. 09 x 10(-2) mmol/l, with
      the use of a glass cylinder was employed to produce aqueous flare elevation in
      pigmented rabbits. Clonidine was topically administered and yohimbine was
      injected intravenously. Aqueous flare was measured with a laser flare cell meter.
      Topical instillation of 0.25% clonidine inhibited 89% of PGE(2)-induced aqueous
      flare elevation. Instillation of clonidine at 60 or 30 min before and 10 min
      after PGE(2) inhibited flare significantly. Pretreatment with intravenous
      yohimbine decreased the clonidine-induced inhibition of the flare elevation in a
      dose-dependent manner. It is possible that the anti-inflammatory action of
      topical clonidine may be mediated partly by alpha(2)-receptors.

PMID- 10971183
TI  - Distribution and isoform characterization of type XII collagen in bovine cornea.
AB  - Streptavidin peroxidase immunohistochemistry and immunoelectron microscopy were
      used to determine the localization of type XII collagen in sections from bovine
      corneas. Type XII collagen extracted from bovine cornea and skin was assayed by
      Western blotting. Immunohistochemical experiments showed that type XII collagen
      was restricted to the corneal stroma; it was not present in corneal epithelium,
      epithelial basement membrane, Descemet's membrane or endothelium. Type XII
      collagen was distributed throughout the corneal stroma, and it was prominently
      localized at the superficial stroma. Immunoelectron-microscopic examination
      demonstrated that type XII collagen was regularly found along the surface of
      banded collagen fibrils with a periodic distribution. By Western blot analysis,
      we observed that extracts from bovine cornea contained both the long and short
      isoforms of type XII collagen, whereas extracts from bovine skin contained only
      the short isoform. The homogeneous distribution and/or presence of the long
      isoform of type XII collagen may be related to the characteristically regular
      arrangement of collagen fibrils and thereby the transparency of corneal tissue.

PMID- 10971184
TI  - Irradiation for inhibition of endothelial cell growth in vitro.
AB  - The clinical effect of ionising radiation on ocular neovascularisations is
      controversial, not only because of the variety of treatment modalities. The aim
      of our study was to investigate an experimental model which allows to evaluate
      radiation parameters and to study the mechanism of the inhibitory effect on
      neoangiogenesis. In vitro experiments were performed using human umbilical vein
      endothelial cells and human corneal keratocytes. The cells were irradiated with
      different doses of photon beam radiation and counted daily after treatment. Cell
      cultures confirmed the efficiency of irradiation in inhibiting proliferation of
      vascular endothelial cells. Radiosensitivity was shown to be higher in vascular
      endothelial cells than in corneal stromal keratocytes. This might be helpful in
      investigating therapy parameters for treating ocular neovascularisations, as well
      as underlying mechanisms.

PMID- 10971185
TI  - Mitochondria of retinal Muller (glial) cells: the effects of aging and of
      application of free radical scavengers.
AB  - Age-related changes of mitochondria were studied in Muller (retinal glial) cells
      from guinea pigs fed with or without externally applied Ginkgo biloba extract EGb
      761, an established radical scavenger. When Muller cell mitochondria from aged
      animals were compared with those from young adults, they displayed (1) a
      diminished number of well-defined cristae at the ultrastructural level, (2) a
      reduced membrane potential, as revealed by fluorimetry using the voltage
      sensitive dye tetramethyl rhodamine methylester, and (3) a slightly reduced index
      of vitality assayed by tetrazolium salt colorimetry. Muller cell mitochondria
      were also studied in aged guinea pigs which had been fed daily by EGb 761 during
      the last 2 months before they were sacrificed. Such mitochondria displayed (1)
      many well-defined cristae at the ultrastructural level, and, compared with
      mitochondria from untreated aged animals, (2) a significantly enhanced membrane
      potential and (3) a significantly enhanced index of vitality. No age- or drug
      related changes were observed in the mitochondrial content of GABA transaminase,
      as revealed by immunocytochemistry/densitometry. These results suggest that many
      but not all structural and functional parameters of aging Muller cell
      mitochondria are impaired by accumulating oxidative damage, and that externally
      applied radical scavengers may protect the organelles from the damaging actions
      of free radicals. As it has been shown earlier that EGb 761 treatment enhances
      the intrinsic glutathione content of aged guinea pig Muller cells, the protective
      radical-scavenging effect of the drug may be mediated both directly and
      indirectly.

PMID- 10971186
TI  - Epidemiological study of nontraumatic phakic rhegmatogenous retinal detachment.
AB  - We studied the epidemiological characteristics of nontraumatic phakic
      rhegmatogenous retinal detachment (RRD) in a defined population of Split-Dalmatia
      County, Croatia. A total of 278 eyes of 272 patients developed RRD during an 11
      year period, 1988-1998, with a population of 465,947. The annual incidence was
      5.4 per 100,000 population. The mean age of patients was 58.3 years, and the sex
      distribution corresponded with that in the general population. There was
      insignificant preponderance of right eye involvement. Bilaterality was observed
      in 2.2%. The presence of myopia was diagnosed in 46.9% eyes.

PMID- 10971187
TI  - Relationship between formation of a filtering bleb and an intrascleral aqueous
      drainage route after trabeculectomy: evaluation using ultrasound biomicroscopy.
AB  - We evaluated the relationship between the development of filtering bleb and the
      thickness of the aqueous drainage route beneath the scleral flap in patients who
      had undergone trabeculectomy. The relationship between the postoperative
      intraocular pressure and the size of the filtering bleb was also studied. We
      studied 29 eyes of 21 patients who had been followed for at least 1 (mean 9.9)
      month after the trabeculectomy. Ultrasound biomicroscopy was used to examine the
      filtering bleb and aqueous drainage route beneath the scleral flap. The thickness
      of the aqueous drainage route beneath the center of the scleral flap was found to
      be correlated with the development of a filtering bleb (r = 0.391, p < 0.05). The
      size of the bleb was correlated with the intraocular pressure (r = -0.560, p <
      0.05) which had not been treated with antiglaucoma medication during follow-up.
      Thus, preservation of the aqueous drainage route beneath the scleral flap
      probably influenced the development of a filtering bleb following trabeculectomy.

PMID- 10971188
TI  - Effect of insulin-like growth factors 1 and 2, and glucose on the migration and
      proliferation of bovine retinal pigment epithelial cellsin vitro.
AB  - BACKGROUND: The retinal pigment epithelium (RPE) has been implicated in the
      development of diabetic retinopathy and it has been suggested that insulin-like
      growth factors (IGF) and glucose may be among those factors which are responsible
      for the RPE changes in diabetics. The purpose of this study was to investigate
      the effect of IGF-1, IGF-2, and glucose on the migration and proliferation of
      bovine RPE cells in vitro. METHODS: Primary cultures of bovine RPE cells were
      established from freshly enucleated eyes and passages 5-8 were used for these
      experiments. RPE cell migration was studied in confluent RPE cultures grown in
      multiwell plates. After inhibition of proliferation with mitomycin C (10
      microg/ml) and partial denudation of the RPE in each well, the cells were
      incubated with IGF-1 (10 ng/ml), IGF-2 (10 ng/ml) or glucose (10 mM). Migration
      was measured as the number of cells that had entered the denuded area after 20 h.
      RPE cell proliferation was determined by [(3)H]-thymidine incorporation after
      incubation with IGF-1, IGF-2, and glucose for 24 h. Statistical analysis was
      performed with the paired Student's t test. RESULTS: Exposure of RPE cells to IGF
      1, IGF-2, and glucose resulted in a significantly higher RPE cell migration as
      compared to the control medium (p < 0.008) with 21, 20, 17, and 9 cells/raster
      field, respectively. Additionally, IGF-1 (p = 0.004) and IGF-2 (p = 0.008) but
      not glucose caused a statistically significant stimulation of DNA synthesis with
      761, 747, and 593 ccpm, respectively, as compared to the negative control (352
      ccpm). CONCLUSION: This study indicates that IGF-1 and IGF-2 influence RPE cell
      migration and proliferation. This is further evidence that these factors are
      among those which have to be kept in mind when trying to modulate the development
      of diabetic eye diseases.

PMID- 10971189
TI  - Recovery of intellectual ability following traumatic brain injury in childhood:
      impact of injury severity and age at injury.
AB  - Traumatic brain injury (TBI) may have a profound impact on a child's ongoing
      development. Various risk factors have been found to predict outcome, but
      considerable variability remains unexplained. This study used a prospective,
      longitudinal design to examine the relationship between recovery, injury
      severity, age at injury and pre-injury ability. 124 children were divided
      according to (1) age at injury: 'young' (3-7 years) 'old' (8-12) and (2) injury
      severity (mild, moderate, severe). Children were evaluated acutely (T1) and at 12
      months post-injury (T2), using standardized intellectual measures (IQ). Results
      showed a relationship between greater injury severity and poorer IQ. Age at
      injury was not predictive of outcome for children with mild/moderate TBI. For
      severe TBI, younger age at injury led to minimal recovery in IQ, while recovery
      from later injury was similar to that for adults. Findings suggest that children
      sustaining severe TBI in early childhood may be particularly at risk for residual
      problems post-injury.

PMID- 10971190
TI  - An unusual case of traumatic intracranial hemorrhage caused by wakeboarding.
AB  - Wakeboarding is a relatively new and exciting sporting activity which is similar
      to water-skiing. While there have been several reports of water-skiing-related
      injuries, there has been nothing reported in the literature so far concerning
      injuries in wakeboarding. We present the case of a 14-year-old male who sustained
      an unusual intracranial subdural hemorrhage while wakeboarding and postulate on
      the mechanisms which could have resulted in the injury.

PMID- 10971191
TI  - Spinal lipomas in children.
AB  - Spinal cord lipomas are a common cause of cord tethering that can lead to
      progressive neurological defects. The role of prophylactic surgery for spinal
      lipomas has recently been questioned. Between 1985 and 1999, 59 children
      underwent a total of 69 surgical procedures at the Birmingham Children's Hospital
      in Birmingham, UK. The spinal lipomas were classified into: 18 terminal, 17
      transitional, 6 dorsal and 18 filum lipomas - including 12 who had a typical
      thickened filum terminale. At the first operation, 19 patients (32%) were
      asymptomatic, and 40 patients (68%) presented with symptoms. Surgical indications
      in the asymptomatic group included the presence of a dermal sinus tract or
      syrinx. Prophylactic surgery was undertaken in selected cases. The mean total
      follow-up for the group since the first surgical procedure was 61.8 months
      (range: 7.0-203.0 months). In the asymptomatic group, 26% of the patients had
      late neurological deterioration. Of the 14 patients with asymptomatic conus
      lipomas, 3 (21%) developed sphincter dysfunction and motor problems at long-term
      follow-up. In the symptomatic group, 68% improved, 20% remained unchanged, and
      12% had late neurological deterioration. None of the 18 patients with symptomatic
      filum lipoma deteriorated postoperatively. However, 39% had bladder dysfunction,
      54% had neuro-orthopaedic deformity, and only 15% returned to overall normal
      function at latest follow-up. Of the 27 patients with symptomatic conus lipomas,
      67% improved, 15% remained stable, and 18% had late neurological deterioration.
      However, 74% had bladder dysfunction, 67% had neuro-orthopaedic deformity, and
      45% had motor problems at long-term follow-up. Spinal lipomas can cause
      progressive neurological deficits irrespective of spinal untethering surgery.
      This study demonstrates that filum and conus lipomas have similar clinical
      presentation, but differ in their outcome following surgery. Filum lipomas are
      'benign', for which surgery is safe and effective. Conus lipomas are more
      difficult to manage. When asymptomatic, our results suggest that prophylactic
      surgery does provide some protection from future neurological deterioration. When
      symptomatic, conus lipoma surgery is effective in stopping further deterioration.
      Improvement in neurological function can occur, but few patients return to normal
      overall function, and pre-existing sphincter dysfunction is not significantly
      altered by surgery.

PMID- 10971192
TI  - MR venography in children with complex craniosynostosis.
AB  - PURPOSE: Chronic venous hypertension due to jugular foramen stenosis has been
      proposed as an etiology for the hydrocephalus and tonsillar herniation seen in
      some patients with complex craniosynostosis. We report the use of MR venography
      (MRV) to evaluate venous outflow obstruction in this clinical setting. MATERIALS
      AND METHODS: We studied 17 patients, (ages 4 months to 34 years; mean 7.3 years)
      with complex craniosynostosis; 8 patients with Crouzon's syndrome, 2 with
      Apert's, 1 with Pfeiffer's and 6 patients without an eponymous classification. MR
      imaging included routine imaging sequences and axial 2D TOF MRV. Patterns of
      venous drainage and the presence of hydrocephalus and tonsillar herniation were
      noted. RESULTS: Jugular vein obstruction was seen in 12/17 patients; in 5/8
      patients with Crouzon's, 1/2 with Apert's, the single patient with Pfeiffer's and
      5/6 patients with nonsyndromic craniosynostosis. The predominant collateral
      drainage was via the posterior condylar veins. Nine of 12 (75%) of the patients
      with abnormal MRV had hydrocephalus; 3/8 patients with Crouzon's, 1/2 patients
      with Apert's, and 5/6 nonsyndromic patients. Two patients had hydrocephalus with
      normal MRV. Ten patients had tonsillar herniation, which was associated with
      shunted hydrocephalus in 7/10 patients, and hydrocephalus seen prior to shunt
      placement in 3/9. Nine of 10 patients with tonsillar herniation had an abnormal
      MRV, while 1 patient had a normal MRV. Venous pressures measured in 1 patient
      showed an 8-mm-Hg differential across the skull base. CONCLUSIONS: The posterior
      condylar veins appear pivotal in maintaining venous drainage when the jugular
      bulbs are occluded. Although the association between venous outflow obstruction,
      hydrocephalus and tonsillar herniation is intriguing, evidence of venous outflow
      obstruction by MRV may not be indicative of significant intracranial venous
      hypertension.

PMID- 10971193
TI  - Hippocampal sclerosis in a two-year-old with temporal lobe epilepsy: case report
      with pathological confirmation.
AB  - The case of a 2-year-old girl who underwent anterior temporal lobectomy for
      intractable epilepsy is described. Hippocampal sclerosis (HS) was present on
      histopathological examination. We believe this to be one of the youngest reported
      patients with pathologically confirmed HS. This has implications for the possible
      etiology of HS.

PMID- 10971195
TI  - Cerebral mantle recovery after shunting.

PMID- 10971194
TI  - What causes childhood brain tumors? Limited knowledge, many clues.
AB  - Little is known about the causes of brain tumors in children. Children with one
      of several genetic disorders including tuberous sclerosis and Li-Fraumeni
      syndrome are at increased risk, as are children who have received therapeutic
      irradiation to their head. The multifactorial causation of brain tumors, the
      inaccuracies of recall of past exposures, and the study of all pediatric brain
      tumors as a single etiologic entity may be contributing to the difficulty in
      identifying additional risk factors. The evidence that frequent cured meat
      consumption by the mother during pregnancy increases the risk is suggestive but
      not conclusive. For other potential risk factors, the evidence is limited and/or
      conflicting. These exposures and characteristics include pesticides, carcinogen
      metabolizing genes, and polyomaviruses.

PMID- 10971196
TI  - Hydromyelia in a child with chiari II.

PMID- 10971197
TI  - Introduction

PMID- 10971199
TI  - Genetic polymorphism of thiopurine S-methyltransferase: molecular mechanisms and
      clinical importance.
AB  - The activity of thiopurine S-methyltransferase (TPMT) is inherited as an
      autosomal co-dominant trait. In most large world populations studied to date,
      approximately 10% of the population have intermediate activity due to
      heterozygosity at the TPMT locus, and about 0.33% is TPMT deficient. TPMT is now
      one of the most well characterized genetic polymorphisms of drug metabolism, with
      the genetic basis having been well defined in most populations, providing
      molecular strategies for studying this genetic polymorphism in human and
      experimental models. Three mutant alleles, TPMT(*)2, TPMT(*)3A and TPMT(*)3C,
      account for the great majority of mutant alleles in all human populations studied
      to date. Significant ethnic differences occur in the frequencies of these mutant
      alleles. Progress in DNA analysis has made it practical to use genotyping
      techniques for the molecular diagnosis of TPMT deficiency and heterozygosity,
      thereby avoiding adverse effects that are more prevalent in TPMT-deficient and
      heterozygous patients prescribed thiopurine medications.

PMID- 10971198
TI  - The evolution of drug metabolism.
AB  - So-called 'drug-metabolizing enzyme' (DME) genes have existed on this planet for
      more than 2.5 billion years and would be more appropriately named 'effector
      metabolizing enzymes'. Genes encoding DMEs have functioned in many fundamental
      processes in prokaryotes and, more recently, in countless critical life processes
      in plants and animals. DME genes exist in every eukaryotic cell and in most, if
      not all, prokaryotes. Over the past decade, it has become clear that each person
      has their own 'individual fingerprint' of unique alleles coding for DMEs. The
      underlying genetic predisposition of each patient reflects combinations of poor-
      and extensive-metabolizer phenotypes. If these enzymes cooperate in the same
      metabolic pathway for any given drug or environmental agent, such ecogenetic
      variability might be synergistic and could cause 30- to > 40-fold differences in
      activation or degradation. The end result can be large interindividual
      differences in risk of environmentally caused toxicity or cancer. Human DME gene
      polymorphisms often show high frequencies of variant alleles. Many factors
      contribute to persistence of these high frequencies, including a combination of
      selective pressures involving diet, climate and geography, as well as 'balanced
      polymorphisms' ('shared benefit' for the heterozygote). However, the extensive
      heterogeneity in the human genome currently being discovered suggests many more
      polymorphisms will occur not only in drug metabolism genes, but in all genes, and
      exhibiting large gene-by-gene variability.

PMID- 10971200
TI  - Applications of genetically manipulated mice in pharmacogenetics and
      pharmacogenomics.
AB  - Gene knockout mice have proven to be very useful in understanding the role of
      xenobiotic-metabolizing enzymes in chemical toxicity and carcinogenesis. The
      combination of gene knockout technology with transgenic mouse technology should
      provide more versatile and suitable animal models to study the risks of chemical
      exposures in humans in terms of toxicity and carcinogenesis, as well as
      development and design of new therapeutic drugs. Recent studies using genetically
      manipulated mice are summarized.

PMID- 10971201
TI  - Glutathione S-transferase polymorphisms and their biological consequences.
AB  - Two supergene families encode proteins with glutathione S-transferase (GST)
      activity: the family of soluble enzymes comprises at least 16 genes; the separate
      family of microsomal enzymes comprises at least 6 genes. These two GST families
      are believed to exert a critical role in cellular protection against oxidative
      stress and toxic foreign chemicals. They detoxify a variety of electrophilic
      compounds, including oxidized lipid, DNA and catechol products generated by
      reactive oxygen species-induced damage to intracellular molecules. An increasing
      number of GST genes are being recognized as polymorphic. Certain alleles,
      particularly those that confer impaired catalytic activity (e.g. GSTM1(*)0,
      GSTT1(*)0), may be associated with increased sensitivity to toxic compounds. GST
      polymorphisms may be disease modifying; for example, in subgroups of patients
      with basal cell carcinoma or bronchial hyper-responsiveness, certain GST appear
      to exert a statistically significant and biologically relevant impact on disease
      susceptibility.

PMID- 10971202
TI  - Pharmacogenetics of beta-1- and beta-2-adrenergic receptors.
AB  - beta(1)- and beta(2)-adrenergic receptors are G protein-coupled receptors
      expressed throughout the body and serve as receptors for the catecholamines
      epinephrine and norepinephrine. They are targets for therapeutive agonists and/or
      antagonists in treatment of heart failure and asthma. Nonsynonymous coding and
      promoter polymorphisms of both receptors have been identified in the general
      population. These have been mimicked in transfected cell systems and transgenic
      mice, and show altered expression, ligand binding, coupling, or regulation
      phenotypes. Clinical studies to date have revealed that some of these
      polymorphisms have a significant disease modifying effect or alter the response
      to treatment. These are some of the first G protein coupled receptor
      polymorphisms to undergo extensive in vitro study and clinical validation; there
      are likely to be polymorphisms of other receptors of the superfamily that will
      have clinical relevance as well.

PMID- 10971203
TI  - The CYP2C19 enzyme polymorphism.
AB  - The genetic test is gradually replacing probe drugs as the primary tool for
      screening populations for the CYP2C19 polymorphism. A full appreciation for the
      clinical and toxicological relevance of this genetic variation is presently
      limited. Further research is needed in several areas. The development and use of
      3-D models of the CYP2C19 enzyme to automate and increase the rate at which
      CYP2C19 substrates are identified could reap great benefits. Meanwhile, clinical
      research should begin to determine whether the CYP2C19 polymorphism affects
      therapeutic outcomes and toxicity of drugs in actual patient settings. Combining
      research efforts in molecular modeling, genetic testing, clinical and
      epidemiological research will be required if better appreciation of this genetic
      variation and its importance in the population at large is to emerge.

PMID- 10971204
TI  - Pharmacogenetics of the alcohol dehydrogenase system.
AB  - Alcohol dehydrogenase (ADH) constitutes a complex enzyme system with different
      forms and extensive multiplicity. A combination of constant and variable
      properties regarding function, multiplicity and structure of ADH is highlighted
      for the human system and extended to ADH forms in general. Future perspectives
      suggest continued studies in specific directions for distinction of metabolic,
      regulatory and pharmacogenetic roles of ADH.

PMID- 10971205
TI  - Polymorphisms of human aldehyde dehydrogenases. Consequences for drug metabolism
      and disease.
AB  - Aldehyde dehydrogenases (ALDHs), a superfamily of NAD(P)(+)-dependent enzymes
      with similar primary structures, catalyze the oxidation of a wide spectrum of
      endogenous and exogenous aliphatic and aromatic aldehydes. Thus far, 16 ALDH
      genes with distinct chromosomal locations have been identified in the human
      genome. Polymorphism in ALDH2 is associated with altered acetaldehyde metabolism,
      decreased risk of alcoholism and increased risk of ethanol-induced cancers.
      Polymorphisms in ALDH3A2, ALDH4A1, ALDH5A1 and ALDH6A1 are associated with
      metabolic diseases generally characterized by neurologic complications. Mutations
      in ALDH3A2 cause loss of enzymatic activity and are the molecular basis of
      Sjogren-Larsson syndrome. Mutations in ALDH4A1 are associated with type II
      hyperprolinemia. Deficiency in ALDH5A1 causes 4-hydroxybutyric aciduria. Lack of
      ALDH6A1 appears to be associated with developmental delay. Allelic variants of
      the ALDH1A1, ALDH1B1, ALDH3A1 and ALDH9A1 genes have also been observed but not
      yet characterized. This review describes consequences of ALDH polymorphisms with
      respect to drug metabolism and disease.

PMID- 10971206
TI  - The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5
      fluorouracil.
AB  - There is increasing evidence supporting the important role of genetics in
      determining the effect (response and toxicity) to cancer chemotherapy. This has
      included both pharmacogenetics, where the alteration of a gene coding for an
      important drug metabolizing enzyme results in increased toxicity (and
      occasionally altered efficacy), and pharmacogenomics, where knowledge of the
      expression of genes critical to the action of the cancer chemotherapy drug can be
      used to individualize therapy. This manuscript focuses on the widely used cancer
      chemotherapy drug 5-fluorouracil (5-FU) to illustrate the following concepts: (1)
      The effect of the pharmacogenetic syndrome known as dihydropyrimidine
      dehydrogenase (DPD) deficiency on 5-FU pharmacology; (2) the role of
      pharmacogenomics in individualizing 5-FU therapy, and (3) the potential value of
      pharmacogenomics in designing new drugs.

PMID- 10971207
TI  - Pharmacogenetics of the human arylamine N-acetyltransferases.
AB  - This review briefly describes current understanding of one of the earliest
      discovered pharmacogenetic polymorphisms of drug biotransformation affecting
      acetylation of certain homo- and heterocyclic aromatic amines and hydrazines.
      This so-called acetylation polymorphism arises from allelic variation in one of
      the two known human arylamine N-acetyltransferase genes, namely NAT2, which
      results in production of NAT2 proteins with variable enzyme activity or
      stability. The NAT1 gene locus encodes a structurally related enzyme, NAT1, with
      catalytic specificity for arylamine acceptor substrates distinct from that
      exhibited by NAT2. NAT1 function is also genetically variable in human
      populations. Clinical and toxicological consequences of genetic variation in NAT1
      and NAT2 activity are discussed.

PMID- 10971208
TI  - Molecular genetics of cancer susceptibility.
AB  - Studies on the role of genetically polymorphic enzymes like cytochrome P450 1A1,
      arylamine N-acetyltransferase 2 or glutathione S-transferase M1 as cancer
      susceptibility factors date back more than 20 years, and some associations have
      been confirmed in several studies and meta-analyses. Overall, the extent of risk
      modulation due to these polymorphisms is only moderate but remains
      epidemiologically relevant. The role of some of these polymorphisms in human
      health may even be ambiguous: rapid acetylation, for example, protects from
      urinary bladder cancer but appears to increase the risk of laryngeal, lung and
      colon cancer. The first genetic polymorphisms in xenobiotics transporters such as
      P-gp (MDR1) and MRP2 have recently been identified. These polymorphisms may have
      great impact as cancer susceptibility factors as well as factors modulating the
      outcome of cancer treatment. Enzymes involved in generation or detoxification of
      reactive oxygen species also have to be considered; one of these enzymes,
      myeloperoxidase, constitutes a relatively strong lung cancer risk factor, as
      confirmed in 4 independent studies. Other genes, including those coding for DNA
      repair enzymes, signal transduction and cell growth regulation, may ultimately
      prove more important than the metabolic enzymes as cancer susceptibility factors.
      Study designs in molecular genetic epidemiology are evolving; large ongoing
      prospective trials increasingly allow confirmatory nested case control studies to
      be performed. However, carefully controlled, large case-control studies will
      remain the mainstay in molecular genetic epidemiology. Molecular genetic
      epidemiological evaluation of response to chemoprevention as well as response to
      the adverse events of cancer chemotherapy are likely to provide results that may
      be useful for individualized prevention and treatment in the near future. Since
      routine genotyping of all persons is now feasible, something like a genotype
      passport may soon become reality, and molecular and clinical epidemiological
      studies will have to provide the basis for understanding how to use genotype data
      for the benefit of the population.

PMID- 10971209
TI  - alphaalpha-crosslinked hemoglobin: was failure predicted by preclinical testing?
AB  - In 1998, Baxter Healthcare announced that it was abandoning its product,
      diaspirin-crosslinked hemoglobin (DCLHb), the first 'blood substitute' to
      complete all phases of human trials. The company announced that the phase III
      (pivotal) trials in humans had resulted in an unexpectedly high survival in a
      group of patients serving as controls for those who received their product in a
      trauma setting. It is not possible to quantitate the time, efforts and money that
      were expended in the course of developing this product, from 1985 to 1998. It is
      rumored that the giant healthcare company had expended more than a half billion
      dollars on this product, not to mention the investment in the same product by the
      US Army, the National Institutes of Health and many independent university-based
      scientists. The disappointment was profound and far-reaching. Although the threat
      of HIV transmission by banked blood has all but disappeared in the developed
      world, still the bulk of the world's population faces blood shortages, which this
      product and its future generations might have helped alleviate. Only Baxter and
      the Food and Drug Administration may forever know key elements of the history of
      development of this product. However, because the US Army decided to make its
      version of the product widely available to scientists, there is a substantial
      published record, contributed to by both Baxter and independent scientists.
      Examination of this record leads to the conclusion that there is no single reason
      for failure. However, it shows that the characteristic hemodynamic response
      caused by alphaalphaHb increased vascular resistance, and probably eliminates its
      potential as a red cell substitute. Newer solutions that overcome this limitation
      should fare better in clinical development when this problem is overcome.

PMID- 10971211
TI  - Leukoreduction of platelet concentrates using a 'polishing' filter.
AB  - BACKGROUND AND OBJECTIVES: Filters for removal of leukocytes from platelet
      concentrates (PCs) usually have a large volume to guarantee sufficient
      leukoreduction. In this study, a small filter, with a volume of only 8 ml and
      therefore minimal platelet loss, for leukoreduction of PCs was investigated. This
      filter has a 'limited' leukoreducing capacity, hence the filter is called a
      'polishing' filter. MATERIALS AND METHODS: PCs were made from 5 pooled buffy
      coats in either plasma or additive solution (PAS-II). After centrifugation, the
      platelet-rich supernatant was expressed on an automated separator (Compomat G4)
      to an empty transfer bag. The content of this transfer bag was filtered into the
      platelet storage bag, either by expression by lowering the top press of the
      Compomat G4, or by gravity by hanging it on a filtration rack. RESULTS: Leukocyte
      counts before and after filtration revealed a mean leukoreducing capacity for the
      filter of 2.67 log(10) and a platelet loss of only 2% for PCs in PAS-II (n = 50),
      and for PCs in plasma a 3.43 log(10) leukoreduction with 3% platelet loss (n =
      30). Expression of the PCs both in plasma and PAS-II through the filter using the
      Compomat G4 resulted in 10/10 units containing <5x10(6) leukocytes, but 1/10 PCs
      contained >1x10(6) leukocytes for both solutions. Filtration by gravity resultet
      in 40/40 units with <1x10(6) leukocytes for PCs in plasma, and 60/60 units with
      <1x10(6) for PCs in PAS-II. CONCLUSION: The 'polishing' filter allows reliable,
      standardized and automated production of PCs, both in plasma and additive
      solution with minimal platelet loss, and containing uniformly <1x10(6)
      leukocytes, provided the filtration procedure is performed by gravity.

PMID- 10971210
TI  - Increase in glycocalicin levels in platelet concentrates stored in plasma or
      synthetic medium for 8 days: comparison with other platelet activation markers.
AB  - BACKGROUND AND OBJECTIVES: Glycocalicin (GC) is a proteolytic fragment of GpIb
      and can conveniently be measured in supernatants of platelet concentrates (PCs)
      by means of a sandwich ELISA. Because of the convenience of the assay and easy
      sample storage, we tested its suitability as a sensitive platelet activation
      parameter during PC storage. MATERIAL AND METHODS: Filtered PCs in plasma or
      additive solution were made from 5 pooled buffy coats and were subsequently
      stored during 8 days at 22+/-2 degrees C. Correlation coefficients (r) were
      calculated after comparison of GC levels with platelet parameters. RESULTS: A
      significant increase in GC concentration was found on all subsequent sampling
      days. PC stored in plasma showed GC levels that correlated well with the soluble
      P-selectin levels (r = 0.7506), P-selectin (CD62P) expression on platelet
      membranes (r = 0. 8843), morphology scores according to Kunicki (r = -0.7102),
      lactate concentrations (r = 0.9216), glucose concentrations (r = -0.8913) and
      beta-thromboglobulin (beta-TG) concentrations (r = 0.8913). In PCs stored in
      additive solution, the correlation coefficients with these markers were 0.9209
      with soluble P-selectin, 0.7161 with CD62P expression, -0.7474 with morphology
      score, -0.8908 with glucose concentrations, 0.8923 with lactate concentrations
      and 0.8908 with beta-TG concentrations. CONCLUSIONS: The GC concentration
      correlates well with sensitive platelet (activation) parameters, rendering it a
      sensitive and convenient parameter for platelet activation.

PMID- 10971212
TI  - Improved sensitivity in the measurement of residual leukocytes in platelet
      products using an automated leukocyte counter.
AB  - BACKGROUND AND OBJECTIVES: Leukocytes remaining in platelet concentrates may be
      responsible for side effects caused by platelet transfusion. A simple method of
      high sensitivity for determining trace numbers of leukocytes is currently needed.
      MATERIALS AND METHODS: An automated leukocyte counter, the LD-1000, the principle
      of which is a combination of spinning down on the observation field of stained
      nuclei derived from a 100 microl neat sample and image digitization with a charge
      coupled device camera, was newly developed and tested for sensitivity and
      reproducibility. RESULTS: While the theoretical lower limit of detection was 0.01
      cells/microl, the limit of detection of the LD-1000 was verified to be 0.2
      cells/microl. A good correlation (r = 0.86) was observed between the results
      obtained using the Nageotte method and the LD-1000. Repeated measurements also
      confirmed satisfactory reproducibility. CONCLUSIONS: The instrument provides a
      new method of enumerating residual leukocytes in platelet products with better
      sensitivity and easier procedure compared to the Nageotte method and will be
      useful for quality assurance purposes at blood centers.

PMID- 10971213
TI  - Erythrocytapheresis with recombinant human erythropoietin in hereditary
      hemochromatosis therapy: a new alternative.
AB  - BACKGROUND AND OBJECTIVES: The purposes of this study were to evaluate the
      tolerance, efficacy and safety of isovolemic erythrocytapheresis (EA) in
      nonanemic patients with hereditary hemochromatosis (HH), and to assess the
      usefulness of recombinant human erythropoietin (rHuEPO) associated with EA to
      reduce treatment duration. MATERIALS AND METHODS: In 10 asymptomatic patients
      with serum ferritin >400 microg/l, transferrin saturation >50%, and GPT
      elevation, EA with rHuEPO and folic acid was performed. RESULTS: Red cell
      indices, serum ferritin, and other iron metabolism parameters (serum iron,
      transferrin, and transferrin saturation); GPT and other laboratory data were
      considerably improved. CONCLUSION: This method offers better results in less time
      than traditional phlebotomy. EA with rHuEPO is an effective therapeutic
      alternative for patients with HH.

PMID- 10971214
TI  - A clinically applicable method for the ex vivo generation of antigen-presenting
      cells from CD34+ progenitors.
AB  - BACKGROUND AND OBJECTIVES: Dendritic cells (DCs), the most potent of antigen
      presenting cells, can be generated in vitro from bone marrow or blood progenitor
      cells. We have developed a method for producing such cells from mobilised
      peripheral blood CD34+ cells in the absence of bovine products. METHODS: The
      culture system developed used X-Vivo 10 culture medium with 10% autologous serum,
      rhGM-CSF, rhTNF-alpha and rhIL-4. Large-scale cultures were performed in
      Stericell 12 inch x 15 inch culture bags. RESULTS: In 12-small-scale experiments,
      over 14 days, there was a median 38-fold increase in cell numbers of which 12.8%
      were DCs as defined by immunophenotyping. These cells had potent DC activity in
      functional assays. In two clinical-scale experiments, a 5.7- and 10-fold
      expansion of total cell numbers was obtained, with 8.2 and 18% of the final
      population being DCs, respectively. CONCLUSION: This system is suitable for
      clinical application.

PMID- 10971215
TI  - Confirmation of the assignment of the Dombrock blood group locus (DO) to
      chromosome 12p: narrowing the boundaries to 12p12.3-p13.2.
AB  - BACKGROUND AND OBJECTIVES: Antigens belonging to the Dombrock blood group system
      have been well characterized serologically. Despite being reasonably polymorphic,
      chromosomal localization of the gene controlling Dombrock expression (DO) has
      proved difficult. In the past, DO had been provisionally assigned to chromosomes
      1 and 4; more recently, DO was provisionally assigned to chromosome 12. The
      current study was undertaken in an attempt to confirm or refute this latest
      assignment. MATERIALS AND METHODS: DNA from a series of families segregating for
      DO was amplified by polymerase chain reaction and analyzed for trinucleotide or
      tetranucleotide repeat polymorphisms of four anonymous DNA markers (D12S1042,
      D12S373, D12S391, D12S372) and of the von Willebrand factor gene (VWF). Lods for
      or against linkage were determined between DO and each marker. RESULTS: DO is
      linked to all five markers. The closest linkage was established between DO and
      D12S373, and DO and D12S391, with peak lods for combined paternal and maternal
      meioses of 7.16 at peak recombination fraction (theta) = 0.08 and 7.69 at theta =
      0.08, respectively. CONCLUSIONS: We have confirmed the assignment of the Dombrock
      blood group locus to chromosome 12p and have refined its regional localization to
      12p12.3-p13.2.

PMID- 10971216
TI  - Transfusion-associated sepsis caused by Candida parapsilosis.
AB  - BACKGROUND AND OBJECTIVES: The contamination of blood components by bacteria is
      an adverse event, which, although very uncommon, has an exceptionally high
      mortality rate. CASE REPORT: A patient suffering from terminal adenocarcinoma of
      the ovary received a red blood cell unit. During the transfusion, the patient
      developed fever. Cultures of both the patient's blood and the blood unit were
      done, and she was treated with antibiotics. Forty-eight and seventy-two hours
      after the transfusion, Candida parapsilosis grew in the blood cultures of the red
      blood cell bag and of the patient. The infection was controlled with
      amphotericin. The patient died from cancer progression. CONCLUSIONS We describe
      the first case of transfusion-associated sepsis caused by C. parapsilosis.

PMID- 10971217
TI  - Sustained increase in arterial blood pressure and vascular resistance induced by
      infusion of arachidonic acid in rats.
AB  - The haemodynamic responses to arachidonic acid (AA) have been investigated in
      seven groups of anaesthetized rats. Sodium arachidonate was infused intravenously
      for 4 or 20 min, and arterial blood pressure was recorded continuously. Cardiac
      output and organ blood flow were measured by microspheres. Infusion of
      arachidonate caused first a fast drop in arterial blood pressure, thereafter it
      increased steadily for 5-15 min towards a pressure about 25 mmHg above control
      level. The high pressure was maintained for at least 1 h. Repeated infusions of
      arachidonate gave similar responses. Inhibition of cyclo-oxygenase by
      indomethacin prevented the initial pressure drop to arachidonate, but not the
      sustained increase in pressure. Arterial pressure, total vascular resistance and
      blood flow in the kidneys, adrenals and spleen were significantly reduced,
      whereas cardiac output was not changed 4 min after start infusion of
      arachidonate. However, average blood pressure was significantly increased 22 and
      35 min after start infusion (from 103.9 +/- 2.9 to 128.1 +/- 6.1 and 135.8 +/-
      4.6 mmHg). Mean vascular resistance increased simultaneously (from 3.5 +/- 0.2 to
      4.7 +/- 0.4 and 5.2 +/- 0.4 mmHg 100 mL-1), while cardiac output, stroke volume
      and heart rate were maintained or slightly reduced. The renal blood flow was
      significantly lowered (from average 4.9 +/- 0.1 to 3.3 +/- 0.2 and 4.0 +/- 0.2 mL
      min-1). Indomethacin did not prevent the changes in vascular resistance or organ
      blood flow recorded after 20-35 min. On the other hand, inhibition of both cyclo
      oxygenase, lipoxygenase and the cytochrome P450 pathways by eicosatetrayonic acid
      (ETYA) normalized all haemodynamic parameters. Likewise, the rise in pressure was
      prevented by 17-octadecynoic acid (17-ODYA), an inhibitor of the cytochrome P450
      enzyme activity. Thus, arachidonate infusion caused a transient decrease, and
      then a sustained increase in arterial pressure and vascular resistance, and a
      long-lasting reduction in renal blood flow, possibly owing to release of a
      cytochrome P450 dependent vasoconstrictor metabolite of AA.

PMID- 10971218
TI  - Lactoferrin and anti-lactoferrin antibodies: effects of ironloading of
      lactoferrin on albumin extravasation in different tissues in rats.
AB  - Lactoferrin is a cationic iron-binding protein, which is released from activated
      neutrophils in concert with reactive oxygen species. In vitro, lactoferrin has
      both anti- and proinflammatory effects; many of them dependent on iron-binding.
      In vivo, only iron-free lactoferrin reduced inflammatory hyperpermeability in the
      lung. We therefore examined whether 1 mg iron-free (Apo-Lf) or iron-saturated
      lactoferrin (Holo-Lf) alone or followed by anti-lactoferrin antibodies (aLf)
      affected permeability evaluated by extravasation of radiolabelled bovine serum
      albumin (CBSA) in different tissues of anaesthetized rats. Fifteen minutes after
      i.v. injection of Lf, aLf or saline was given and circulatory arrest was induced
      20 min thereafter. Measurements were performed in control, after Apo-Lf, Holo-Lf,
      Apo-Lf + aLf, Holo-Lf + aLf and aLf alone (n=6-8 in each group). No intergroup
      differences were found for plasma volume and haematocrit at the start and end of
      the 37 min extravasation period or for total tissue water in any of the six
      different tissues studied, excluding larger transcapillary fluid shifts. However,
      increases in CBSA were seen without differences in tissue intravascular volume.
      Iron-free lactoferrin and aLf alone did not change CBSA significantly. Iron
      saturated lactoferrin significantly increased CBSA in skin (neck), trachea and
      left ventricle of the heart to 249 +/- 9, 284 +/- 16 and 160 +/- 7% of control,
      respectively. When followed by aLf, both Apo- and Holo-Lf increased CBSA
      significantly in four and five of the tissues studied, respectively. However, no
      significant effect was seen for Holo-Lf + aLf compared with Holo-Lf alone. In
      conclusion, iron-saturated, but not iron-free lactoferrin increased CBSA, whereas
      antilactoferrin increased CBSA compared with lactoferrin alone only when
      following iron-free lactoferrin.

PMID- 10971219
TI  - Differential recruitment of alpha 1- and beta-adrenoceptors in inotropic control
      of atrial child myocardium by endogenous noradrenaline.
AB  - Noradrenaline release, graded by frequency variation of field stimulation (0.1-2
      Hz), in atrial myocardial specimens (n=45) from children (n=21) with congenital
      heart defects, was used to examine the inotropic responses of graded, receptor
      selective, endogenous stimulation. Muscle trabeculae subjected to autonomic
      blockage by timolol, prazosin and atropine showed a slight positive force
      frequency relationship (staircase phenomenon). Blockage by atropine/prazosin
      (i.e. beta-adrenoceptor stimulation) or atropine/timolol (i.e. alpha1
      adrenoceptor stimulation) both resulted in positive inotropic effects. A group of
      specimens opposed by atropine and primarily subjected to frequency variation,
      secondly was returned to 1 Hz. Stabilization was followed by sequential reversal
      by beta-blocker (timolol), alpha 1-adrenoceptor stimulation by exogenous
      noradrenaline, reversal by alpha 1-blocker (prazosin), and finally supramaximal
      beta-adrenoceptor stimulation (isoprenaline). The maximal levels of inotropic
      responses mediated by exogenous alpha 1- and beta-adrenoceptor stimulation was
      estimated. Analysis of the contraction-relaxation cycles revealed that alpha1-
      and beta-adrenoceptors were recruited differentially. The alpha1-adrenoceptor
      mediated, endogenous inotropic effect at 1 Hz was close to the level obtained by
      exogenous noradrenaline stimulation. In contrast, less than 70% of the beta
      adrenoceptor mediated, exogenous inotropic effect was expressed by endogenous
      noradrenaline at the same stimulating frequency, thus indicating that the alpha1
      adrenoceptors may be located closer to the adrenergic nerve terminals than the
      beta-adrenoceptors. There may be a heterogeneous relationship within the same
      heart as to the relative distance between the nerve terminals and the
      adrenoceptors. Spatial localization of adrenergic receptors relative to
      adrenergic nerve terminals adds another aspect to adrenergic regulation. The
      alpha1-adrenoceptor pathway may play an important role, especially in low
      intensity sympathetic inotropic myocardial control, whereas the beta-adrenoceptor
      pathway adds important effects to the high-intensity sympathetic regulation.
      Sympathetic activity may thus tonically stimulate the alpha1-adrenoceptor
      pathway, without necessarily stimulating the beta-adrenoceptor pathway to the
      same extent.

PMID- 10971221
TI  - Hyperbaric oxygen increases parasympathetic activity in professional divers.
AB  - The role of autonomic nervous system in hyperoxic bradycardia was evaluated by
      using the power-spectral analysis of heart-rate variability (HRV). Ten
      professional divers went through two hyperbaric hyperoxic experiments: (1)
      hyperbaric oxygen (HBO), 100% oxygen at 2.5 ATA, (2) hyperbaric air (HBAIR), O(2)
      21% at 2.5 ATA. Four-minute traces of ECG were registered and subjected to power
      spectral analysis. Cardiac conduction parameters were evaluated by a diagnostic
      12-lead ECG and arrhythmias by a continuous 3-lead ECG. Statistical analysis was
      made using analysis of variance for repeated measurements. Heart rate decreased
      (P < 0. 001), but the response was similar during both treatments (P=0.14). Total
      power increased significantly more during HBO than HBAIR (P=0.003). High
      frequency (HF) power (P < 0.001), Hayano's index (P=0.001) and normalized units
      of HF power (P=0.002) increased and LF/HF index (P < 0.001) decreased more during
      HBO than HBAIR. There were no changes in cardiac conduction or incidence of
      arrhythmias. In conclusion, 100% oxygen at 2.5 ATA caused marked increase in
      parasympathetic tone compared with 21% oxygen at 2.5 ATA.

PMID- 10971220
TI  - Middle cerebral artery blood velocity during exercise with beta-1 adrenergic and
      unilateral stellate ganglion blockade in humans.
AB  - A reduced ability to increase cardiac output (CO) during exercise limits blood
      flow by vasoconstriction even in active skeletal muscle. Such a flow limitation
      may also take place in the brain as an increase in the transcranial Doppler
      determined middle cerebral artery blood velocity (MCA V(mean)) is attenuated
      during cycling with beta-1 adrenergic blockade and in patients with heart
      insufficiency. We studied whether sympathetic blockade at the level of the neck
      (0.1% lidocaine; 8 mL; n=8) affects the attenuated exercise - MCA V(mean
      following cardio-selective beta-1 adrenergic blockade (0.15 mg kg(-1) metoprolol
      i.v.) during cycling. Cardiac output determined by indocyanine green dye
      dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V(mean) were
      obtained during moderate intensity cycling before and after pharmacological
      intervention. During control cycling the right and left MCA V(mean) increased to
      the same extent (11.4 +/- 1.9 vs. 11.1 +/- 1.9 cm s(-1)). With the
      pharmacological intervention the exercise CO (10 +/- 1 vs. 12 +/- 1 L min(-1);
      n=5), HR (115 +/- 4 vs. 134 +/- 4 beats min(-1)) and delta MCA V(mean) (8.7 +/-
      2.2 vs. 11.4 +/- 1.9 cm s(-1) were reduced, and MAP was increased (100 +/- 5 vs.
      86 +/- 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck
      eliminated the beta-1 blockade induced attenuation in delta MCA V(mean) (10.2 +/-
      2.5 cm s(-1)). These results indicate that a reduced ability to increase CO
      during exercise limits blood flow to a vital organ like the brain and that this
      flow limitation is likely to be by way of the sympathetic nervous system.

PMID- 10971222
TI  - Differential activation of mitogen-activated protein kinase signalling pathways
      by isometric contractions in isolated slow- and fast-twitch rat skeletal muscle.
AB  - Activation of mitogen-activated protein (MAP) kinases has been implicated in the
      signal transduction pathways linking exercise to adaptive changes of muscle
      protein expression. In the present study, we investigated whether contractions of
      isolated muscles induced phosphorylation of extracellular signal-regulated kinase
      1 and 2 (ERK1/2) and p38 MAPK in a fibre-type dependent manner. Slow-twitch
      (soleus) and fast-twitch (epitrochlearis, extensor digitorum longus) rat skeletal
      muscles were exposed to intermittent tetanic stimulation. Compared with the
      contralateral non-stimulated muscle, contractions increased ERK1/2
      phosphorylation to the same extent in fast- and slow-twitch muscles. Significant
      increase in phosphorylation of p38 MAPK was observed in the fast-twitch muscles
      only. The total amount of ERK1/2 and p38 MAPK proteins was higher in the slow
      twitch soleus muscle. In conclusion, MAP kinase signalling pathways are
      differentially activated and expressed in slow- and fast-twitch muscles. In
      addition, this activation is owing to muscle contraction per se and do not demand
      additional external influence.

PMID- 10971223
TI  - Age-related differences in twitch contractile properties of plantarflexor muscles
      in women.
AB  - This study compared maximal voluntary isometric strength and electrically evoked
      twitch characteristics of the plantarflexor muscles among the groups of women of
      the 3rd (n=14), 4th (n=13), 5th (n=11), 6th (n=12) and 8th (n=13) decade. A
      significant decrease (P < 0.05-0.001) has been found in isometric maximal
      voluntary contraction (MVC) force from the 5th decade and in twitch maximal force
      from the 6th decade. The 3rd decade group produced 72% greater MVC force and 43%
      greater twitch maximal force than the 8th decade group (P < 0.001). A
      prolongation (P < 0.01) in twitch contraction time was observed from the 5th
      decade. Twitch contraction time in the 3rd decade group was 16% shorter (P <
      0.001) compared with the 8th decade group (P < 0.01). Twitch half-relaxation time
      did not differ significantly (P > 0.05) among the groups. A decrease (P < 0. 05
      0.001) has been found in twitch maximal rate of force development from the 5th
      decade and in twitch maximal rate of relaxation from the 6th decade. The 3rd
      decade group produced 63% greater (P < 0. 001) twitch maximal rate of force
      development than the 8th decade group. It was concluded that in women a marked
      age-related reduction in maximal voluntary force-generating capacity of the
      plantarflexor muscles and speed of contraction of the electrically evoked twitch
      takes place after 40 years of age, while reduction in maximal force-generating
      capacity and speed of relaxation of the twitch occurs after 50 years of age.

PMID- 10971224
TI  - Expression of the Na(+)/H(+) exchanger isoform NHE1 in rat skeletal muscle and
      effect of training.
AB  - The expression of the Na(+)/H(+) exchanger isoform NHE1 was quantified in
      homogenates of various rat skeletal muscles by means of immunoblotting, and the
      effect of 3 weeks of treadmill training on NHE1 expression was determined in a
      red (oxidative) as well as a white (glycolytic)-muscle preparation. The NHE1
      antibodies recognized a glycosylated protein at 101-111 kDa. There was a positive
      correlation between the NHE1 expression in the muscle and percent type IIB fibres
      and percent type IID/X fibres, whereas the NHE1 expressions were negatively
      correlated to percent type I fibres and percent type I + IIA fibres. Thus the
      highest NHE1 expression was evident in the most glycolytic fibres. Treadmill
      training increased (P < 0.05) the NHE1 content by 29 and 36% in oxidative and
      glycolytic fibres, respectively, suggesting that training enhanced the NHE1
      content of all muscle-fibre types. Therefore training may improve the capacity
      for pH regulation in skeletal muscle.

PMID- 10971225
TI  - Differential changes in corticospinal and Ia input to tibialis anterior and
      soleus motor neurones during voluntary contraction in man.
AB  - Motor-evoked potentials (MEPs) were recorded in the tibialis anterior and soleus
      muscles following transcranial magnetic stimulation (TMS) of the motor cortex. In
      the soleus, the H-reflex amplitude increased with the contraction level to the
      same extent as that of MEPs, whereas in the tibialis anterior, the H-reflex
      amplitude increased significantly less than that of MEPs. The latency of the MEPs
      decreased with contraction, whereas this was not the case of the H-reflexes. In
      the tibialis anterior, the response probability of single-motor units (SMU) to
      TMS increased more substantially during voluntary contraction than following
      stimulation of the peroneal nerve. In the tibialis anterior, the response
      probability of SMU increased more substantially during voluntary contraction than
      following stimulation of the peroneal nerve. The short-latency facilitation,
      presumably monosynaptic of origin, of the soleus H-reflex evoked by subthreshold
      TMS increased as a function of the plantarflexion force. This was not the case
      for the heteronymous Ia facilitation of the soleus H-reflex following stimulation
      of the femoral nerve. It is concluded that the corticospinal input to lower limb
      motor neurones generated by TMS increases with the level of voluntary
      contraction, whereas this is true only to a limited extent for the synaptic input
      from Ia afferents. It is suggested that this reflects changes in the
      susceptibility of corticospinal cells to TMS during voluntary contraction.

PMID- 10971226
TI  - Review article: Helicobacter pylori vaccines-the current status.
AB  - In this review, we take a look at the current status in the development of a
      vaccine against the human pathogenic bacterium, Helicobacter pylori, a major
      aetiological factor in peptic ulcer disease and gastric adenocarcinoma. Various
      animal models are now in use from mice infected with H. pylori, through
      gnotobiotic pigs and primates to ferrets naturally infected with their own
      Helicobacter, H. mustelae. A significant problem remains the requirement for a
      suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants
      already available may provide a solution and new immune stimulating compounds
      have been tested with some success. New approaches include the delivery of
      Helicobacter antigens by DNA immunization, microparticles or live vectors such as
      attenuated salmonella and the examination of alternative routes of vaccine
      administration. The phenomenon of post-immunization gastritis and improvements in
      vaccine efficacy are also discussed. A major area of interest is the mechanism by
      which immunization actually influences Helicobacter colonization. This remains a
      mystery: antibodies appear to be unimportant whereas CD4+ T-cells essential.
      Finally, a viewpoint is given on whom should be immunized when a final vaccine
      becomes available.

PMID- 10971227
TI  - Acid suppression in peptic ulcer haemorrhage: a 'meta-analysis'.
AB  - BACKGROUND: The use of acid-decreasing agents in the management of peptic ulcer
      haemorrhage continues to be controversial. Most clinical trials examining the
      efficacy of these drugs contain small numbers of patients, making it difficult to
      draw conclusions about their efficacy. METHODS: We report a meta-analysis that
      examined the effect of these drugs in the management of peptic ulcer haemorrhage.
      Included studies were located using a search of the Medline database between 1980
      and 1999. Studies were published in English, randomized and controlled by a
      placebo group. Mantel-Haenszel and blinded random models were used in conducting
      the statistical processing of this meta-analysis. RESULTS: Twenty-one randomized
      placebo-controlled trials were included. The total number of patients was 3566
      and the mean study size was 170 (range 20-1005). Seventeen of the papers assessed
      the efficacy of H2-antagonists, three assessed proton pump inhibitors and one was
      concerned with antacid therapy. The meta-analysis showed a significant reduction
      in re-bleeding rates (odds ratio, OR 0.727, 0.618-0.855, P < 0.001) and surgery
      rates (OR 0.707, 0.582-0.859, P < 0.001) when acid decreasing agents are used for
      acute peptic ulcer haemorrhage. Mortality rates appear to be unaffected (OR
      1.140, 0.818-1.588, P=0. 49). CONCLUSIONS: This meta-analysis demonstrates a
      significant beneficial effect of acid-decreasing agents in lowering re-bleeding
      and surgery rates, but demonstrated no effect upon mortality.

PMID- 10971228
TI  - Role of antibiotic therapy on long-term germ excretion in faeces and digestive
      symptoms after Salmonella infection.
AB  - BACKGROUND: The role of antibiotic therapy on Salmonella faecal excretion is
      controversial. Acute Salmonella gastroenteritis induces long-lasting digestive
      symptoms in up to one-third of subjects. The role of antimicrobial therapy on
      persistent post-infectious symptoms is unknown. AIM: To investigate the role of
      antibiotic therapy on long-term germ faecal excretion and digestive symptoms
      after Salmonella infection. SUBJECTS AND METHODS: 1543 subjects [518 aged between
      3 and 5 years (35.3%); 950 between 6 and 10 years (64.7%) and 75 adults (4.9%)]
      involved in a single outbreak of Salmonella enteritis fulfilled the study
      criteria by repeating stool cultures and answering a symptom questionnaire 3
      months post-infection. RESULTS: 327 subjects (21.2%) were treated with
      antibiotics during the acute infection [121 children aged 3-5 years (23.4%), 175
      children aged 6-10 years (18.4%) and 31 adults (41.3%)]. Antibiotic treatment did
      not affect Salmonella excretion at any of the time points studied up to three
      months post-infection in any age group as compared to age-matched untreated
      controls. Persistent digestive symptoms were more common among the patients
      treated with antibiotics (9.5% vs. 2.9%; P=0.003). CONCLUSIONS: Antibiotic
      therapy does not affect Salmonella enteritis excretion. Digestive symptoms after
      clearance of the infectious agent are significantly higher in patients treated
      with antibiotics during acute gastroenteritis.

PMID- 10971229
TI  - Bioavailability of four ursodeoxycholic acid preparations.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) is the drug of choice for treating
      primary biliary cirrhosis and dissolving cholesterol gallstones. OBJECTIVES: The
      objective of this study was to compare the bioavailability of four commercially
      available ursodeoxycholic acid formulations in standardized doses. METHODS:
      Twenty-four healthy subjects were studied in groups of four, and received each of
      the different UDCA preparations in random order, with a 1-week washout or more in
      between. Serum UDCA levels were determined for a 6-h period. The mean area under
      the curve (AUC), Cmax and Tmax were determined for each drug formulation, and the
      results compared. Dose proportionality was determined using the Canadian Ursofalk
      tablet using either 250 mg, 500 mg or 750 mg dosing. The intraparticipant
      variability was assessed by asking each participant to repeat the last drug that
      they took the second time, 1 week later. RESULTS: The mean AUC was 68.99
      micromol/1.6 h-1 for the USA UDCA tablet, 59.34 micromol/1.6 h-1 for the Canadian
      UDCA tablet, 55.55 micromol/1.6 h-1 for Ursolvan capsules, and 46.66 micromol/1.6
      h-1 for Actigall capsules. The mean Cmax values were 24.29, 17.85, 16.63 and
      413.32 nmol/mL, respectively. The mean Tmax was 1.82, 2.3, 2.79 and 3.39 h,
      respectively. Linear aggression analysis assessing the direct proportionality of
      AUC on the dose for the Canadian UDCA tablet gave an estimate of 0.063 + 0.0164
      (standard error, P-value=0.0117), e.g. if the dose increases from 250 mg to 500
      mg, the serum ursodeoxycholic acid increases by 250 x 0.063=15.75. There was
      excellent reproducibility for the AUC for the North American tablets (0.97, 0.88)
      compared to the two capsules (0.32, 0.15). CONCLUSIONS: The significantly higher
      AUC and Cmax and shorter Tmax for the Canadian Ursofalk tablets compared to the
      UDCA capsule preparations supports better bioavailability.

PMID- 10971230
TI  - Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine bismuth
      citrate plus two antibiotics for 1 week-a meta-analysis of efficacy.
AB  - OBJECTIVE: To compare the efficacy of proton pump inhibitor vs. ranitidine
      bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori
      eradication. METHODS: Randomized trials comparing 1-week regimens with (i) proton
      pump inhibitor plus two antibiotics [clarithromycin (C) and amoxycillin (A) or a
      nitroimidazole (N)]; or (ii) RBC plus the same antibiotics. Eradication was
      confirmed by histology or 13C-urea breath test at least 4 weeks after therapy.
      Data sources included PubMed database and abstracts from congresses until October
      1999. Statistical analysis was by meta-analysis combining the odds ratios (OR) of
      the individual studies in a global OR (Peto method). RESULTS: Twelve studies met
      the selection criteria. Nine compared proton pump inhibitor vs. RBC plus C and A,
      and five compared proton pump inhibitor vs. RBC plus C and N. With RBC, C and A,
      mean H. pylori eradication efficacy by intention-to-treat analysis (pooled data)
      was 76.6% (95% CI: 72-81%) and 73.7% (95% CI: 69-78%) with proton pump inhibitor,
      C and A. The OR for the effect of RBC vs. proton pump inhibitor (plus C and A) on
      H. pylori eradication was 1.15 (95% CI: 0.8-1.64%). Mean H. pylori eradication
      with RBC, C and N was 87. 2% (95% CI: 83-91%), and 74.9% (95% CI: 74-84%) with
      proton pump inhibitor plus these two antibiotics. The OR for the effect of RBC
      vs. proton pump inhibitor (plus C and N) on H. pylori eradication was 1.76 (95%
      CI: 1.08-2.85%). CONCLUSION: RBC and proton pump inhibitor have similar efficacy
      for H. pylori eradication when given with C and A for 1 week, but RBC seems to
      have a higher efficacy than proton pump inhibitor when C and N are the co
      prescribed antibiotics.

PMID- 10971232
TI  - Allopurinol in addition to 5-aminosalicylic acid based drugs for the maintenance
      treatment of ulcerative colitis.
AB  - BACKGROUND: To investigate the value of combined treatment with allopurinol and 5
      aminosalicylic (5-ASA) based drugs as maintenance treatment for ulcerative
      colitis (UC). METHODS: 199 patients with UC in remission but with active disease
      during the preceding 3 years were included. Allopurinol 100 mg twice daily or
      placebo was added to the 5-ASA based maintenance treatment. Clinical and
      endoscopic follow up was performed after 1, 6 and 12 months. RESULTS: Intention
      to-treat analysis after 6 and 12 months showed similar results in both groups. A
      log-rank test showed that 77% in the allopurinol compared to 59% in the placebo
      group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12
      months, respectively (P=0.0936). This was mainly due to a higher than expected
      number of relapses during the first 3 months in the placebo group. After the
      first 3 months, the rate of relapse in each group was similar. CONCLUSIONS: It
      appears possible that allopurinol in combination with 5-ASA is better than 5-ASA
      alone for a 6-month, but not a 12-month period. This has to be verified in
      further dose-ranging studies.

PMID- 10971231
TI  - Eradication of Helicobacter pylori with pantoprazole and two antibiotics: a
      comparison of two short-term regimens.
AB  - BACKGROUND: High rates of Helicobacter pylori eradication can be achieved by
      combining proton pump inhibitors with two antibiotics. However, in the search for
      an optimal therapy a direct comparison of different regimens is necessary.
      METHODS: For this open study, 331 patients with duodenal ulcer were screened and
      randomly allocated to either pantoprazole 40 mg b.d., clarithromycin 500 mg b.d.,
      and metronidazole 500 mg b.d. (PCM) or pantoprazole 40 mg b.d., amoxycillin 1000
      mg b.d., and clarithromycin 500 mg b.d. (PAC) for 7 days. Both combinations were
      followed by a 7-day therapy with pantoprazole 40 mg o.d. alone. Eradication of H.
      pylori was assessed by use of a 13C-urea breath test 4 weeks after the intake of
      the last medication. RESULTS: Eradication rates were 90% in intention-to-treat
      patients from the PCM (132 out of 147; 95% CI: 84-94%) and the PAC group (135 out
      of 150; 95% CI: 84-94%). H. pylori was eradicated in 112 out of 117 per protocol
      patients of the PCM group (96%; 95% CI: 90-99%) and in 119 out of 126 patients of
      the PAC group (94%; 95% CI: 89-98%). Rapid relief from ulcer pain and a decrease
      in the mean intensity of other gastrointestinal symptoms was observed. Sixty-nine
      patients reported adverse events, none of which were related to the intake of
      pantoprazole. Four serious adverse events, none related to the trial medication,
      were observed. CONCLUSIONS: Both pantoprazole-based short-term triple therapies
      are highly effective and well-tolerated treatment regimens in the eradication of
      H. pylori.

PMID- 10971233
TI  - Effects of iron and iron chelation in vitro on mucosal oxidant activity in
      ulcerative colitis.
AB  - BACKGROUND: Reactive oxygen species may be pathogenic in ulcerative colitis. Oral
      iron supplements anecdotally exacerbate inflammatory bowel disease and iron
      levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion
      production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine,
      is reportedly beneficial in Crohn's disease. AIMS: To assess the in vitro effects
      of exogenous iron and of iron chelators on the production of reactive oxygen
      species by colonic biopsies from normal control subjects and patients with
      ulcerative colitis. METHODS: Luminol-amplified chemiluminescence was used to
      measure mucosal reactive oxygen species production both before and after addition
      in vitro of ferric citrate (100 microM), desferrioxamine (1 mM) and 1,10
      phenanthroline (1 mM). RESULTS: Ferric citrate had no effect on the
      chemiluminescence produced by human colonic mucosa. However, desferrioxamine and
      phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10,
      P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0.
      008) and 42% (n=11, P=0.006) in active disease. CONCLUSION: The lack of effect of
      ferric citrate suggests that sufficient free iron is already present in inflamed
      biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine
      and 1,10-phenanthroline on the chemiluminescence of biopsies from patients with
      ulcerative colitis suggest that a clinical trial of topical iron chelation in
      active disease is indicated.

PMID- 10971234
TI  - Inhibition of platelet activation by 5-aminosalicylic acid in inflammatory bowel
      disease.
AB  - BACKGROUND: Platelets play an important role in inflammation and are activated in
      inflammatory bowel disease. Micro-vascular thrombosis in the gut wall leading to
      intestinal micro-infarction may be a pathogenic feature of Crohn's disease. 5
      Aminosalicylic acid is an effective treatment for patients with inflammatory
      bowel disease. AIMS: To assess the effects of 5-aminosalicylic acid on platelet
      activation, when taken orally and in vitro by patients with inflammatory bowel
      disease. METHODS: Spontaneous and thrombin-induced platelet activation were
      studied using fluorescent antibodies to the activated platelet surface
      glycoprotein P-selectin and flow cytometry. RESULTS: Baseline platelet activation
      in inflammatory bowel disease was significantly greater than that in controls
      (P=0.0003). Independent of diagnosis or disease activity, spontaneous ex-vivo
      platelet activation was 50% lower in patients with inflammatory bowel disease
      taking 5-aminosalicylic acid orally than in those not on such treatment (P <
      0.05). In vitro, 5-aminosalicylic acid significantly reduced both spontaneous (P
      < 0. 03 for >/=1 microM 5-aminosalicylic acid) and thrombin-induced platelet
      activation (P < 0.02 for >/= 1 microM 5-aminosalicylic acid). CONCLUSIONS: 5
      Aminosalicylic acid given either orally or in vitro inhibits platelet activation.
      If this effect reflects an in vivo action in the gut, it could contribute to the
      beneficial actions of 5-aminosalicylic acid in inflammatory bowel disease.

PMID- 10971235
TI  - The effect of unfiltered coffee on potential biomarkers for colonic cancer risk
      in healthy volunteers: a randomized trial.
AB  - BACKGROUND: Epidemiologic studies suggest that coffee use might protect against
      colorectal cancer. Inconsistencies as to the effect of coffee use and colorectal
      cancer between epidemiologic studies might be related to the type of coffee brew.
      OBJECTIVE: We studied the effect of unfiltered coffee consumption on putative
      biomarkers for colonic cancer risk. DESIGN: A total of 64 healthy volunteers (31
      men and 33 women), with a mean age of 43 +/- 11 years were randomly assigned to
      two groups in a crossover design, with two intervention periods of 2 weeks
      separated by a washout period of 8 weeks. Treatments were 1 L of cafetiere
      (French press) coffee daily or no coffee. At the end of each intervention period,
      fasting blood samples, colorectal biopsies and 48 h faeces were collected.
      RESULTS: No effect of coffee on colorectal cell proliferation, assayed by
      estimating the Proliferating Cell Nuclear Antigen labelling index, was seen.
      Additionally, no effects were seen on the concentrations of faecal soluble bile
      acids and colorectal mucosal glutathione S-transferase activity. However,
      unfiltered coffee significantly increased the glutathione content in the
      colorectal mucosa by 8% and in plasma by 15%. Other aminothiols in plasma also
      increased on coffee. CONCLUSION: Unfiltered coffee does not influence the
      colorectal mucosal proliferation rate, but might increase the detoxification
      capacity and anti-mutagenic properties in the colorectal mucosa through an
      increase in glutathione concentration. Whether this effect indeed contributes to
      a lower colon cancer risk remains to be established.

PMID- 10971236
TI  - Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal
      ulcerative colitis: a double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Rectal formulations of mesalazine are the treatment of choice in
      mildly to moderately active ulcerative colitis. A new foam formulation of
      mesalazine was developed to improve both drug delivery and patient acceptance.
      METHODS: In this multicentre, randomized, double-blind, parallel-group study, 111
      patients with mildly to moderately active proctitis, proctosigmoiditis, or left
      sided ulcerative colitis received mesalazine foam enema or placebo enema (2 g
      mesalazine per day) for 6 weeks. Disease activity was monitored on the basis of
      the Clinical Activity Index, Endoscopic Index, Histological Index, and global
      efficacy assessment by the investigators. Safety assessments included the
      recording of adverse events, laboratory variables and vital signs. RESULTS:
      Clinical remission was more frequent in the mesalazine group than the placebo
      group (65% vs. 40%; P=0.0082), particularly in patients with mild disease and
      patients with proctosigmoiditis. The frequency of patients with an endoscopic
      remission was higher in the mesalazine group (57%) than in the placebo group
      (37%). Similarly, 59% of patients receiving mesalazine but only 41% of those
      receiving placebo showed an improved Histological Index. The foam enemas were
      generally well-tolerated, and no treatment-related changes on laboratory
      variables and vital signs were noted. CONCLUSIONS: Mesalazine foam enema was well
      tolerated and was more effective than placebo in the treatment of patients with
      distal ulcerative colitis.

PMID- 10971237
TI  - Parkinsonism: differential age-trend in Helicobacter pylori antibody.
AB  - BACKGROUND: Parkinsonism is associated with prodromal peptic ulceration. Dopamine
      antagonists provoke experimental ulcer, dopaminergic agents protect, and might
      inhibit growth of Helicobacter pylori. OBJECTIVE: To describe the relationship
      between H. pylori serology and parkinsonism. METHODS: Serum H. pylori anti-urease
      IgG antibody was measured in 105 people with (idiopathic) parkinsonism, 210
      without, from same locality. None had received specific eradication therapy.
      RESULTS: Controls showed a birth-cohort effect: antibody titre rose from 30 to 90
      years (P < 0. 001). Parkinsonism obliterated this (disease status. age
      interaction, P < 0.05), the differential age trend not being attributable to
      social class. Those with diagnosed parkinsonism were more likely to be
      seropositive (odds ratio 2.04 (95% CI: 1.04, 4.22) P < 0.04) before 72.5 years.
      Overall, titre fell (P=0.01) by 5 (1, 9)% per unit increase in a global, 30-point
      rating (median 14 (interquartile range 10.5, 17)) of disease severity. No
      individual category of anti-parkinsonian medication (92% taking) had a
      differential lowering effect. CONCLUSIONS: Higher prevalence of seropositivity in
      parkinsonism, before 8th decade, may be due to host susceptibility/reaction, or,
      conversely, infection with particular H. pylori strain(s) lowering dopaminergic
      status. Absence of a birth cohort effect in parkinsonism, despite similar social
      class representation, may be consequent on eradication, spontaneous (gastric
      atrophy) or by anti-parkinsonian medication.

PMID- 10971238
TI  - Sedation with propofol plus midazolam versus propofol alone for interventional
      endoscopic procedures: a prospective, randomized study.
AB  - AIM: Adequate patient sedation is mandatory for most interventional endoscopic
      procedures. Recent anaesthesiologic studies indicates that propofol and midazolam
      act synergistically in combination and therefore may be superior to sedation with
      propofol alone in terms of sedation efficacy, recovery and costs (due to a
      presumed lower total dose of propofol needed). METHODS: A total of 239
      consecutive patients undergoing therapeutic EGD or ERCP (EGD/ERCP-ratio, 1:1)
      randomly received either propofol alone (n=120, group A, loading dose 40-60 mg
      intravenously, followed by repeated doses of 20 mg) or propofol plus midazolam
      (n=119, group B, initial midazolam dose of 2. 5-3.5 mg intravenously, followed by
      repeated doses of 20 mg of propofol) for sedation. Vital signs (heart rate, blood
      pressure, oxygen saturation, electrocardiogram) were continuously monitored.
      Procedure-related parameters, the recovery time and quality (post-anaesthesia
      recovery score) as well as the patient's co-operation and tolerance to the
      procedure (visual analogue scale) were prospectively assessed. RESULTS: Patients
      of group A and B were well matched with respect to demographic and clinical data,
      endoscopic findings, and the type of associated procedures. In group A, a mean
      dose of 0.25 +/- 0.13 mg.min/kg propofol was used compared to 0.20 +/- 0.09
      mg.min/kg of propofol in group B (P < 0.01, plus additional 2.9 +/- 0.5 mg of
      midazolam). Clinically relevant changes in vital signs were observed at
      comparable frequencies with a lowering of the systolic blood pressure < 90 mmHg
      in six out of 119 patients in group B and one out of 120 patients in group A
      (P=0.07). The sedation efficacy was rated similarly in both groups, whereas the
      mean recovery time (group A, 19 +/- 7 min vs. group B, 25 +/- 8 min, P < 0.05) as
      well as the recovery score (post-anaesthesia recovery score group A, 8.0 +/- 1.1
      vs. post-anaesthesia recovery score group B, 7.3 +/- 1.2, P < 0.001) were
      significantly better with propofol alone than with propofol plus midazolam.
      CONCLUSION: During therapeutic endoscopy, sedation with propofol and midazolam
      requires a lower total dose of propofol, but otherwise has no superior sedation
      efficacy and is associated with a slower post-procedure recovery than sedation
      with propofol alone.

PMID- 10971239
TI  - Gastric damage in the rat with nitrogen-containing bisphosphonates depends on pH.
AB  - BACKGROUND: The use of nitrogen-containing bisphosphonates (N-BPs) has been
      reported to be associated with gastrointestinal intolerance. The fasted,
      indomethacin-treated rat provides a model for assessing the gastrointestinal
      effects of these compounds. AIMS: The aims of this study were to elucidate the
      effect of pH on N-BP-induced gastric damage, and to evaluate the structure
      activity relationship between N-BP anti-resorptive and gastric effects. METHODS:
      Fasted rats were dosed concomitantly with indomethacin (40 mg/kg, subcutaneously)
      and an N-BP (pamidronate, alendronate, or risedronate at 150 or 300 mg/kg,
      orally), with the N-BP dosing solutions adjusted to pH 2, 4 or 7. The
      aminopentane and aminohexane N-BPs (150, 225 or 300 mg/kg, orally) were only
      tested at pH 4 only. RESULTS: Nitrogen-containing bisphosphonate-induced gastric
      damage was pH-dependent, with increased damage at increasing pH. CONCLUSIONS:
      Gastric damage potential did not correlate with bone anti-resorptive effects, and
      the more potent anti-resorptive N-BPs were not necessarily more damaging to the
      stomach.

PMID- 10971240
TI  - Initial potency of lansoprazole and omeprazole tablets on pentagastrin-stimulated
      gastric acid secretion-a placebo-controlled study in healthy volunteers.
AB  - BACKGROUND: The new tablet formulation of omeprazole (Losec MUPS), is thought to
      have a stronger acid inhibition than the previously marketed capsules. METHODS:
      The effects of the proton pump inhibitors lansoprazole and omeprazole tablets on
      pentagastrin-stimulated acid secretion were compared in Helicobacter pylori
      negative healthy male volunteers (n=12). The study was placebo-controlled,
      crossover matched and double-blind for lansoprazole (Agopton) and placebo, and
      single-blind for omeprazole tablets. Gastric acid response to sub-maximal
      pentagastrin-stimulation (0.6 microg. h/kg b.w.) was determined from 12.5 to 14.5
      h after the first and second dose of the test drugs. RESULTS: Lansoprazole 15 mg
      and 30 mg as well as omeprazole 20 mg tablets caused a marked decrease in gastric
      acid secretion, showing equipotency for 15 mg lansoprazole and 20 mg omeprazole
      tablets. Their efficacy, however, was lower than 30 mg lansoprazole. In addition,
      the inter-individual variation after omeprazole tablets was higher than following
      lansoprazole. Neither 7.5 mg lansoprazole nor 10 mg omeprazole tablets were
      clearly different from placebo on the first 2 days. The drugs were well
      tolerated. No clinically relevant influence was found on either laboratory screen
      or cardiovascular parameters. CONCLUSION: Lansoprazole 15-30 mg shows a stronger
      acid inhibition and a lower inter-individual variability than the new omeprazole
      20 mg tablets on days 1 and 2 of dosing.

PMID- 10971241
TI  - Sensorless flow and head estimation in the VentrAssist rotary blood pump.
AB  - Flow rate and pressure difference (or head) are key variables needed in the
      control of implantable rotary blood pumps. However, use of flow and/or pressure
      probes can decrease reliability and increase system power consumption and
      expense. For a given fluid viscosity, the flow state is determined by any 2 of
      the 4 pump variables: Flow, pressure difference, speed, and motor input power can
      be used. Thus, if viscosity is known or if its influence is sufficiently small,
      flow rate and pressure difference can be estimated from the motor speed and motor
      input power. For the VentrAssist centrifugal blood pump, which uses a
      hydrodynamic bearing, sensorless flow and pressure head estimation accuracy of 2
      of our impeller designs were compared for a viscosity range of 1.2 to 4.5 mPas.
      This showed impeller design optimization can improve estimation accuracy. We also
      compared estimation accuracy using 2 blood analogues used in vitro, aqueous
      glycerol and red blood cells suspended in Haemaccel. The nature of the blood
      analogue and not only the viscosity of the fluid seems to influence estimation
      accuracy in our pump.

PMID- 10971242
TI  - Physical model-based indirect measurements of blood pressure and flow using a
      centrifugal pump.
AB  - This article describes a technique offering indirect measurements of pump
      pressure differential and flow with certain accuracy independent of changes in
      blood viscosity. This technique is based on noninvasive measurements of the motor
      current and rotation speed using the physical model equations of the centrifugal
      pump system. Blood viscosity included in the coefficients of the dynamic
      equations is first estimated, and then substitution of the estimated viscosity
      into the steady equations of the model provides pump flow and pressure
      differential. In vitro tests using a Capiox pump showed a sufficient linear
      correlation between actual values and their estimates for pressure differential
      and pump flow. An in vivo test using a 45 kg sheep showed that the proposed
      algorithm needs robustness for the convergence of estimates of viscosity. An
      overall evaluation, however, of the developed algorithm/model showed indications
      of success in terms of efficient computation and modeling.

PMID- 10971243
TI  - Control strategy for biventricular assistance with mixed-flow pumps.
AB  - A left ventricular assist device (LVAD) is an effective method to rescue severe
      heart failure. Although some require a biventricular assist, the control method
      for the biventricular assist device (BVAD) with a rotary pump is rarely shown.
      The objective of this study was to investigate the strategy for controlling BVAD
      with rotary pumps by in vivo studies. Using 5 piglets, we set a BVAD through a
      left thoracotomy and made global ischemia for 30 min by clamping the base of the
      ascending aorta. After unclamping, the analysis of pumping performance acted for
      6 h reperfusion. We set the target flow of the LVAD and set the right ventricular
      assist device (RVAD) speed limit as less than when the atrial collapse occurs. To
      detect the ventricular collapse without any specific sensor, we calculated the
      index of current amplitude from motor current waveform and simultaneous mean
      current value. In all cases, over 6 h of observation was performed, and the RVAD
      was weaned almost automatically.

PMID- 10971244
TI  - Sensorless controlling method for a continuous flow left ventricular assist
      device.
AB  - We originated a novel control strategy for a continuous flow left ventricular
      assist device (LVAD). We examined our method by acute animal experiments to
      change the left ventricular (LV) contractility or LV end-diastolic pressure
      (LVEDP). To estimate the pump pulsatility without any specific sensor, we
      calculated the index of current amplitude (ICA) from motor current waveform. The
      ICA had a peak point (t-i point) that corresponded closely with the turning point
      from partial to total assistance, and a trough (s-i point) that corresponded with
      the beginning point of ventricular collapse. The pump flow at the t-i point (Qt
      i) had no component of flow regurgitation. In the evaluation of the effects of
      preload LVEDP, afterload (mAoP), and contractility (max LV dp/dt), we found that
      preload was the only parameter that significantly influenced Qt-i. We concluded
      that our method could well control continuous flow LVAD by preventing reversed
      flow and ventricular collapse.

PMID- 10971245
TI  - Continuously maintaining positive flow avoids endocardial suction of a rotary
      blood pump with left ventricular bypass.
AB  - This study showed the usefulness of maintaining positive pump flow to avoid
      endocardial suction and as an assist bypass. Three calves were implanted with
      centrifugal pumps. Hemodynamics and pump parameters were measured at varying pump
      speeds (from 1,100 to 2,300 rpm). In each test pump, speed was adjusted to create
      3 hemodynamic states: both positive and negative flow (PNF), positive and zero
      flow (PZF), and continuously positive flow (CPF). The pump flow volume was
      determined during systole (Vs) and diastole (Vd). Vs in PNF was 29.6 ml and was
      not significantly different from Vs in PZF (p > 0.15). Vd in PNF was
      significantly different from Vd in PZF (p < 0.05). All bypass rates of PNF were
      over 30% of pulmonary flow. All PZF bypass rates were between the PNF rate and
      the CPF rate. These data showed that PZF satisfied the minimum requirement of
      assist flow and was under 100% bypass. Thus, PZF may avoid endocardial suction.

PMID- 10971246
TI  - Clinical evaluation of heparin-coated circuits for routine coronary artery bypass
      grafting surgery: a prospective randomized study.
AB  - The aim of this study was to demonstrate the clinical and biological benefits of
      heparin-coated circuits in routine coronary artery bypass grafting (CABG). A
      prospective, randomized study was conducted in 80 patients undergoing routine
      CABG. Patients were randomized to either noncoated circuits (Group 1) or heparin
      coated circuits (Group 2). A complete clinical evaluation was performed
      preoperatively at Days 0, 1, 2, and 3 and at discharge day and combined with
      extensive laboratory tests for hemostasis and inflammatory response. This study
      did not prove any major statistically significant clinical benefit of heparin
      coated circuits in low risk patients. Postoperative bleeding, significantly less
      in the heparin-coated group, did not decrease significantly the number of
      transfused patients. Biological values were not changed significantly except for
      factor II and monocytes, which were higher in Group 2. Heparin-coated circuits
      offer minimal clinical and biological benefits for routine CABG surgery. However,
      they may prove beneficial for complex procedures or at-risk patients.

PMID- 10971247
TI  - Effect of wall hardness on hemolysis.
AB  - One of the major problems for artificial organs to develop and to improve is the
      reduction of hemolysis. The optimum designing of less hemolysis artificial organs
      is achieved through computational analysis and flow visualization techniques.
      However, it is impossible to know the quantitative relation between hemolysis and
      these analytic data. Thus, in vitro studies were performed to estimate these
      devices on hemolysis because there is no standard for designing these devices
      with less hemolysis. Therefore, it is essential to reveal the relation between
      blood flow behaviors and hemolysis. Previous studies reported that hemolysis was
      caused by a combination of physical factors. In particular, shear stress,
      pressure, and other fluid dynamical effects were shown to induce hemolysis. In
      another fluid dynamical experiment reported, the collision flow against the
      sanded wall was considered the most important factor that directly effected blood
      damage, which led to hemolysis. The blood flow impact of the collision against
      the wall effected serious damage to red blood cells. The objective of this study
      was to point out the relationship between physical force (pressure) in collision
      flow and hemolysis. In vitro tests using bovine blood and a circulation model
      that included a jet flow that collides against a wall were conducted. In these
      tests, we changed the material of the wall by replacing silicone rubber of
      various thicknesses. The thickness of the silicone rubber is inversely
      proportional to its hardness. The results show that the increasing rate of
      hemolysis was lower when the surface was coated by silicone rubber. In
      conclusion, we considered that it is possible to reduce hemolysis by adjusting
      the hardness of the material and contacted blood flow.

PMID- 10971248
TI  - Biocompatibility of heparin-coated extracorporeal bypass circuits: new heparin
      bonded bioline system.
AB  - Biocompatibility of a new type of heparin-coated cardiopulmonary bypass
      equipment, the Bioline, was evaluated in coronary artery bypass surgery cases.
      The heparin-coated (H) group (n = 15; Quadrox Bioline oxygenator/reservior and
      Carmeda BioMedicus BP-80 centrifugal pump) was compared with the nonheparin
      coated (N) group (n = 12; uncoated, otherwise similar oxygenator, centrifugal
      pump, tubing, and filter set). Both groups used full systemic heparinization. The
      peak values of neutrophil elastase, C3a, IL-6, and IL-8 at 2 h after
      cardiopulmonary bypass (CPB), and C3a levels at the end of CPB and at 2 h after
      CPB were significantly reduced in the H group compared with those of the N group.
      However, no statistically significant intergroup differences were observed in
      thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, or platelet factor
      4. No significant differences were observed in hemostasis time, postoperative 12
      h blood loss, required amount of blood transfusion, or intubation time. In
      conclusion, the Bioline demonstrated partially improved biocompatibility, in
      terms of leukocyte and complement activation, and proinflammatory cytokine
      production. However, it did not improve platelet activation, coagulation, or
      fibrinolysis cascade under full systemic heparinization. As a result, the
      clinical beneficial impact seemed to be the minimum.

PMID- 10971249
TI  - Engineering analysis of diamond-like carbon coated polymeric materials for
      biomedical applications.
AB  - Diamond-like carbon (DLC) films have received much attention recently owing to
      their properties, which are similar to diamond: hardness, thermal conductivity,
      corrosion resistance against chemicals, abrasion resistance, good
      biocompatibility, and uniform flat surface. Furthermore, DLC films can be
      deposited easily on many substrates for wide area coat at room temperature. DLC
      films were developed for applications as biomedical materials in blood contacting
      devices (e.g., rotary blood pump) and showed good biocompatibility for these
      applications. In this study, we investigated the surface roughness by Atomic
      Force Microscopy (AFM) and Hi-vision camera, SEM for surface imaging. The DLC
      films were produced by radio frequency glow discharge plasma decomposed of
      hydrocarbon gas at room temperature and low pressure (53 Pa) on several kinds of
      polycarbonate substrates. For the evaluation of the relation between deposition
      rate and platelet adhesion that we investigated in a previous study, DLC films
      were deposited at the same methane pressure for several deposition times, and
      film thickness was investigated. In addition, the deposition rate of DLC films on
      polymeric substrates is similar to the deposition rate of those deposited on Si
      substrates. There were no significant differences in substrates' surface
      roughness that were coated by DLC films in different deposition rates (16-40 nm).
      The surface energy and the contact angle of the DLC films were investigated. The
      chemical bond of DLC films also was evaluated. The evaluation of surface
      properties by many methods and measurements and the relationship between the
      platelet adhesion and film thickness is discussed. Finally, the presented DLC
      films appear to be promising candidates for biomedical applications and merit
      investigation.

PMID- 10971250
TI  - Transient rise in serum soluble Fas (APO-1/CD95) in patients undergoing cardiac
      surgery.
AB  - The Fas molecule, also designated APO-1/CD95, belongs to the tumor necrosis
      factor (TNF) receptor family. It is a widely expressed membrane-anchored protein
      that induces apoptosis by Fas/Fas ligand (Fas-L) mediation. It was reported that
      Fas-mediated apoptosis plays an important role in regulation of the immune
      system, systemic inflammatory response, and ischemia/reperfusion injury. A
      soluble form of Fas (sFas) is produced either through the proteolytic cleavage of
      membrane-bound receptors or by alternative splicing, and sFas is thought to be
      implicated in apoptosis. In addition, sFas released damaged cells, and elevated
      serum levels of sFas reflect systemic tissue damage. To examine the specificity
      of sFas production during cardiac surgery with cardiopulmonary bypass, we
      serially measured the serum sFas levels in 13 patients during and after surgery.
      Blood samples were obtained before surgery, at the end of cardiopulmonary bypass,
      at the end of surgery, and at 12 h after surgery. Levels of serum sFas were
      determined by sandwich ELISA. Seven patients undergoing other types of surgeries
      served as controls. Although increased sFas was not observed in the control
      group, a significantly higher sFas level was detected in cardiac surgical
      patients at the end of surgery than before surgery (p = 0. 028), and the level
      decreased at 12 h after surgery. A significant correlation was observed between
      the maximum sFas values and the length of surgery (r = 0.659, p = 0.012) and
      cardioplegic arrest (r = 0.559, p = 0.046). Elevated serum sFas levels were
      observed in patients undergoing cardiac surgery, and these serum sFas levels
      reflect the severity of a surgery. sFas may play an important role in the
      pathophysiology of surgical damage caused by cardiac surgery with cardiopulmonary
      bypass.

PMID- 10971251
TI  - Evaluation of cardiac function during left ventricular assist by a centrifugal
      blood pump.
AB  - In this study, the effects on varying cardiac function during a left ventricular
      (LV) bypass from the apex to the descending aorta using a centrifugal blood pump
      were evaluated by analyzing the left ventricular pressure and the motor current
      of the centrifugal pump in a mock circulatory loop. Failing heart models (preload
      15 mm Hg, afterload 40 mm Hg) and normal heart models (preload 5 mm Hg, afterload
      100 mm Hg) were simulated by adjusting the contractility of the latex rubber left
      ventricle. In Study 1, the bypass flow rate, left ventricular pressure, aortic
      pressure, and motor current levels were measured in each model as the centrifugal
      pump rpm were increased from 1,000 to 1,500 to 2,000. In Study 2, the pump rpm
      were fixed at 1,300, 1,500, and 1,700, and at each rpm, the left ventricular peak
      pressure was increased from 40 to 140 mm Hg by steps of 20 mm Hg. The same
      measurements as in Study 1 were performed. In Study 1, the bypass flow rate and
      mean aortic pressure both increased with the increase in pump rpm while the mean
      left ventricular pressure decreased. In Study 2, a fairly good correlation
      between the left ventricular pressure and the motor current of the centrifugal
      pump was obtained. These results suggest that cardiac function as indicated by
      left ventricular pressure may be estimated from a motor current analysis of the
      centrifugal blood pump during left heart bypass.

PMID- 10971252
TI  - Strategy of circulatory support with percutaneous cardiopulmonary support.
AB  - We evaluated the efficacy and problems of circulatory support with percutaneous
      cardiopulmonary support (PCPS) for severe cardiogenic shock and discussed our
      strategy of mechanical circulatory assist for severe cardiopulmonary failure. We
      also described the effects of an alternative way of PCPS as venoarterial (VA)
      bypass from the right atrium (RA) to the ascending aorta (Ao), which was used
      recently in 3 patients. Over the past 9 years, 30 patients (20 men and 10 women;
      mean age: 61 years) received perioperative PCPS at our institution. Indications
      of PCPS were cardiopulmonary bypass weaning in 13 patients, postoperative low
      output syndrome (LOS) in 14 patients, and preoperative cardiogenic shock in 3
      patients. Approaches of the PCPS system were the femoral artery to the femoral
      vein (F-F) in 21 patients, the RA to the femoral artery (RA-FA) in 5 patients,
      the RA to the Ao (RA-Ao) in 3 patients, and the right and left atrium to the Ao
      in 1 patient. Seventeen (56.7%) patients were weaned from mechanical circulatory
      support (Group 1) and the remaining 13 patients were not (Group 2). In Group 1,
      PCPS running time was 33.1 +/- 13.6 h, which was significantly shorter than that
      of Group 2 (70.6 +/- 44.4 h). Left ventricular ejection fraction was improved
      from 34.8 +/- 12.0% at the pump to 42.5 +/- 4.6% after 24 h support in Group 1,
      which was significantly better than that of Group 2 (21.6 +/- 3.5%). In
      particular, it was 48.6 +/- 5.7% in the patients with RA-Ao, which was further
      improved. Two of 3 patients with RA-Ao were discharged. Thrombectomy was carried
      out for ischemic complication of the lower extremity in 5 patients with F-F and 1
      patient with RA-FA. One patient with F-F needed amputation of the leg due to
      necrosis. Thirteen patients (43.3%) were discharged. Hospital mortality indicated
      17 patients (56.7%). Fifteen patients died with multiple organ failure. In
      conclusion, our alternate strategy of assisted circulation for severe cardiac
      failure is as follows. In patients with postcardiotomy cardiogenic shock or LOS,
      PCPS should be applied first under intraaortic balloon pumping (IABP) assist for
      a maximum of 2 or 3 days. In older aged patients particularly, the RA-Ao approach
      of PCPS is superior to control flow rate easily, with less of the left
      ventricular afterload and ischemic complications of the lower extremity. If
      native cardiac function does not recover and longer support is necessary, several
      types of ventricular assist devices should be introduced, according to end-organ
      function and the expected support period.

PMID- 10971253
TI  - Cerebral tissue oxygen saturation during percutaneous cardiopulmonary support in
      a canine model of respiratory failure.
AB  - Percutaneous cardiopulmonary support (PCPS) has come to be applied for
      cardiopulmonary resuscitation and in the management of severe respiratory failure
      as well as severe heart failure. We investigated cerebral tissue oxygen
      saturation during PCPS in a canine model of respiratory failure using near
      infrared spectroscopy. Animals were mechanically ventilated with 10% oxygen to
      make a respiratory failure model. Perfusion with PCPS was performed via the left
      femoral artery and switched to that via the right axillary artery. Cerebral
      tissue oxygen saturation was 54.2 +/- 3.4% during PCPS via the femoral artery and
      was 82.3 +/- 4.6% during PCPS via the axillary artery (p = 0.001). Hepatic tissue
      oxygen saturation was not significantly different. LV dP/dt max increased
      significantly after switching to the axillary blood supply (p = 0.001).
      Conventional PCPS may not have the capability of supporting cerebral circulation
      under severe respiratory failure without organic heart disease.

PMID- 10971254
TI  - Totally implantable ventricular assist system that can increase brain blood flow.
AB  - In the clinical usage of the ventricular assist device (VAD), multiple organ
      failure becomes an important problem. To improve the clinical record of the VAD,
      another organ function may be vitally important. For that reason, we have been
      developing a VAD system aiming at improving another organ's function. Development
      of the vibrating flow pump (VFP), which can generate a very unique flow pattern
      from 10 Hz to 50 Hz, was ongoing in our Institute. In order to evaluate brain
      blood flow and oxygen consumption, HbO2 was measured with a NIRO monitoring
      device in healthy adult goats. Four goats were anesthetized with halothane
      inhalation; then left thoracotomy was performed for the left heart bypass. HbO2
      of the brain was measured by recording of the hemodynamic variables during left
      heart assistance with the VFP system. During left heart bypass with the VFP
      system, hemodynamic parameters stayed within normal range, and satisfactory pump
      output was easily obtained. Pump output stayed within 20-40% bypass to evaluate
      the effect of high frequency oscillated assist flow on brain blood flow during
      the same cardiac output. Interesting results were observed during the
      experiments. During 30 Hz drive of the VFP left heart assistance, HbO2 suggested
      that brain blood flow significantly increased compared with another drive
      frequency assistance during the same total cardiac output. These results suggest
      that we can control the brain blood flow with a totally implantable VAD system
      such as the VFP system.

PMID- 10971255
TI  - Computational fluid dynamics analysis of a centrifugal blood pump with washout
      holes.
AB  - The authors studied avoidance of coagulation occurrence using computational fluid
      dynamics (CFD) analysis from the fluid dynamical point of view. Concerning
      centrifugal pumps, blood coagulation sometimes occurs at the region behind the
      impeller where the flow is generally stagnant. Therefore, we conducted a thorough
      study with the specimen pump with and without washout holes, mocking up the
      Nikkiso HPM-15. As the result, the model with washout holes indicated that the
      fluid rotates rapidly at the vicinity of the shaft and generates washout effects
      near the stationary rear casing. On the other hand, the model without washout
      holes showed that fluid cannot be quickly shipped out of the area behind the
      impeller and rotates mildly around the shaft. To clarify the moving relations
      between the impeller and the fluid, validation studies by comparing the results
      of CFD analysis and flow visualization experiments are ongoing; thus far, the
      studies show that CFD results are similar to the results from flow visualization
      experiments.

PMID- 10971256
TI  - Gyro pump wear and deformation analysis in vivo study: creep deformation.
AB  - The Gyro pump has a double pivot bearing system to support its impeller. In this
      study, the integrity of the bearing system was examined after ex vivo studies.
      The pumps were implanted into calves and evaluated for different periods as a
      paracorporeal left ventricular assist device (LVAD). One pump was subjected to a
      test of 30 days, 1 for 15 days, 4 for 14 days, 1 for 10 days, 1 for 7 days, 2 for
      4 days, and 4 for 2 days. One additional pump was subjected to percutaneous
      cardiopulmonary support (PCPS) condition for 6 days (total pressure head 500 mm
      Hg with a pump flow rate of 3 L/min). The anticoagulation treatment consisted of
      a continuous administration of heparin to maintain an achieved clotting time
      (ACT) of 200-250 s during the LVAD study and 250-300 s during the PCPS study.
      After the experiment, the pumps were disassembled, and the wear and deformation
      of male and female bearings were analyzed. There were no dimensional changes on
      male bearings but there were on female bearings. Wear and deformation of the
      female bearings were calculated as follows: wear and deformation = (depth of
      female before pumping) - (depth after pumping). Thirteen assembled Gyro pumps
      were disassembled to measure the depth of the female bearings before pumping.
      There was no statistical relationship between the wear and deformation and the
      motor speed x driving period. From these results, the deformation was not due to
      wear but to the creep or elastic deformation. This study suggested that the
      double pivot bearing system of the Gyro pump is highly durable.

PMID- 10971257
TI  - Development of a miniature undulation pump for the distributed artificial heart.
AB  - Research of the distributed artificial heart is important not only to acquire the
      means of individual organ perfusion but also to clarify the characteristics of
      the organ and the mechanism of blood distribution. To investigate the distributed
      artificial heart, the miniature undulation pump was developed. The outer diameter
      and the thickness of the developed pump were 38 mm and 11 mm, respectively. The
      priming volume of the pump was 3.2 ml. The total size including the motor unit
      was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total
      volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1
      chip motor controller. More than 5 L/min of continuous output could be obtained.
      The results showed that the developed miniature undulation pump system had enough
      performance for individual organ perfusion.

PMID- 10971258
TI  - Right ventricular assist system feedback flow control parameter for a rotary
      blood pump.
AB  - At least 25-30% of patients with a permanent implantable left ventricular assist
      device (LVAD) experience right ventricular failure; therefore, an implantable
      biventricular assist system (BiVAS) with small centrifugal pumps is being
      developed. Many institutions are focusing and developing a control system for a
      left ventricular assist system (LVAS) with rotary blood pumps. These authors feel
      that the right ventricular assist system (RVAS) with rotary blood pumps should be
      developed simultaneously. A literature search indicated no recent reports on the
      effect of hemodynamics and exercise with this type of nonpulsatile implantable
      RVAS. In this study, a calf with an implantable right ventricular assist system
      (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting
      in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic
      recordings were taken every 5 min throughout the testing period, and blood gas
      analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and
      oxygen extraction (O2ER) were calculated and analyzed. Two different pump flows
      were investigated: Group 1 low assist (<3.5 L/min) and Group 2 high assist (>3.5
      L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary
      artery (PA) flow increased during exercise; also, the heart rate and right atrial
      pressure (RAP) increased during exercise. There were no significant differences
      in the 2 groups. The PA flow correlates to the heart rate during exercise. In all
      of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no
      changes were observed during the different flow conditions; however, the DO2 of
      Group 2 was higher than that of Group 1. Because the implantable RVAS did not
      have pump flow changes during the test conditions, it was necessary to
      incorporate a flow control system for the implantable RVAS. During exercise with
      an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as
      feedback parameters is feasible for controlling the flow rate.

PMID- 10971259
TI  - Antithrombogenicity evaluation of a centrifugal blood pump.
AB  - The Gyro C1E3 pump was developed not only for cardiopulmonary bypass but also as
      a short-term assist device. The main purpose of this study was to examine the
      correlation between the thrombus formation factor and the Gyro C1E3 pumps. Seven
      pumps were implanted into 3 calves and evaluated for different periods of
      duration as a paracorporeal left ventricular assist device (LVAD). One pump was
      subjected to percutaneous cardiopulmonary support condition (PCPS) (total
      pressure head 500 mm Hg with a pump flow rate of 3 L/min). The anticoagulation
      treatment consisted of a continuous administration of heparin to maintain an
      activated clotting time (ACT) of 200-250 during the LVAD study and 250-300 during
      the PCPS study. After the experiment, the pumps were disassembled and examined.
      In cases where there were any blood-derived deposits inside the pumps, the dry
      weight of these thrombi that adhered to the bearing area of the pump was
      measured. A multiple correlation was attempted to speculate possible thrombus
      formation. The estimated dry weight of thrombi was calculated from pump flow
      rate, pumping day, motor speed, and activated clotting time. This equation was
      estimated dry weight of thrombi = 1.140 x pump flow rate -0.001 motor speed +
      1.652 pumping time -0.041 x ACT + 2.198 R2 = 0.944. This study suggested that
      there was a possibility to calculate the amount of adhered thrombus formation
      from pump flow rate, motor speed, pumping day, and ACT.

PMID- 10971260
TI  - Eccentric roller type total artificial heart creating interatrial shunt.
AB  - Creating an interatrial shunt to achieve left-right flow balance and modification
      of the blood chambers to improve the basic performance of the device were
      performed in developing an eccentric roller type total artificial heart (ERTAH).
      Smaller blood chambers reduce friction loss and increase durability and energy
      efficiency. We changed the left blood chamber volume of 60 ml to 40 ml and the
      right blood chamber volume of 53 ml to 35 ml compared with previous types.
      Designs of inlet and outlet ports were modified to prevent backflow. In the mock
      circulatory system, redesigning the blood chambers resulted in a 20% increase in
      energy efficiency, about a two-fold increase of cardiac output and improved
      durability compared to the previous type. In an animal experiment, the ERTAH
      operated at a driving rate of 160 rpm with a left flow rate of 6.0 L/min and a
      right flow rate of 5.4 L/min. Interatrial shunt flow rate was 250-400 ml/min.

PMID- 10971261
TI  - Effects of reduced pulse pressure to the cerebral metabolism during prolonged
      nonpulsatile left heart bypass.
AB  - We investigated changes in the cerebral metabolism with long-term reduced pulse
      pressure. Nine goats underwent pulsatile left heart bypass (LHB) for 2 weeks
      while awake, and nonpulsatile LHB was subsequently conducted for 4 weeks. The
      average pulse pressure during nonpulsatile LHB (13, 10, 11, and 11 mm Hg at the
      1st, 2nd, 3rd, and 4th nonpulsatile LHB week, respectively) was significantly
      lower than that during pulsatile LHB (36 mm Hg). There were no significant
      differences in either arterio-jugular venous oxygen differences (AJDO2) and
      cerebral oxygen extraction ratio between the 2nd pulsatile LHB week and the 1st,
      2nd, 3rd, and 4th nonpulsatile LHB weeks. The arterio-jugular venous glucose
      differences, jugular venous-arterial lactate differences (JAD Lactate), and
      lactate oxygen indexes (JAD Lactate/AJDO2) also remained unchanged during the
      entire course of the experiments. In conclusion, the cerebral metabolism during
      nonpulsatile LHB did not change compared to that during pulsatile LHB.

PMID- 10971262
TI  - Using one rotary blood pump to produce separate pulsatile circulations in the
      upper and lower halves of the body.
AB  - Separate systemic circulations with pulsatile flow were obtained using 1 rotary
      blood pump as a left ventricular assist device. The outlet of the pump was
      divided into 2 conduits, 1 connected to the upper half of the body and the other
      connected to the lower half. An electric actuator that clamped the 2 outlet
      conduits alternately provided pulsatile flows. An in vitro experiment showed that
      the pulsatility phases of the upper and lower halves of the body were
      complementary with pulsatile flow, and an in vivo experiment showed that
      controlled flow distributions of continuous flows could be obtained.

PMID- 10971263
TI  - Whewellite, weddellite and company: where do all the strange names originate?

PMID- 10971264
TI  - A model to quantify encrustation on ureteric stents, urethral catheters and
      polymers intended for urological use.
AB  - OBJECTIVE: To validate an encrustation model and to quantify encrustation on
      currently used urological devices and polymers intended for urological use.
      Materials and methods An encrustation model was validated: (i) to measure the
      amount of calcium leaching from the glass model and from the polymer used; (ii)
      to determine whether the use of a single-source or pooled urine produced similar
      results; (iii) to determine in vitro encrustation; and (iv) to compare the
      results of in vivo implantation of the same materials into the bladders of
      rodents with the in vitro results. A test polymer (a ureteric stent, a urethral
      catheter or a biomaterial) and a control silicone polymer were housed separately
      but received human urine from the same reservoir and under the same conditions
      (pH 6.0 and 37 degrees C) for 5 days. The amount of calcium encrustation on each
      polymer was measured using atomic absorption spectroscopy. Each experiment was
      repeated at least four times and the results expressed as an encrustation index,
      defined as the ratio of encrustation of the test and reference polymers. RESULTS:
      The amount of calcium leaching from the glass model and polymers tested was
      insignificant. The use of a single-source or pooled urine gave the same results
      in the encrustation model. The in vitro results correlated with in vivo
      implantation of disks into the bladders of rats. Among the commonly used ureteric
      stents tested, the Cook C-Flex ureteric stents encrusted least. Hydrogel-coated
      ureteric stents encrusted more than uncoated stents. The Bard
      polytetrafluoroethylene short-term urethral catheter encrusted more than the Bard
      hydrogel-coated long-term catheter. A plasma-activated surface modification of a
      synthetic biomaterial with hyaluronic acid encrusted less than silicone, a long
      term biomaterial widely regarded as the 'gold standard'. CONCLUSION: This
      validated encrustation model is the first to quantify encrustation on currently
      available ureteric stents and urethral catheters. A novel coating for a
      biomaterial was identified using the encrustation model, and which encrusted less
      than silicone.

PMID- 10971265
TI  - Rectal examination and urethral catheterization by medical students and house
      officers: taught but not used.
AB  - OBJECTIVE: To assess the acquisition of skills in digital rectal examination
      (DRE) and urethral catheterization by medical students and house officers
      associated with a UK medical school, and to determine their confidence in these
      techniques. Subjects and methods Questionnaires were sent to all final-year
      medical students at Oxford Medical School immediately before their final
      examinations. Similar questionnaires were sent to all pre-registration house
      officers who had graduated from Oxford in the previous year. RESULTS: Responses
      were received from 71% of the students and 84% of the graduates; 88% of the
      students and 94% of the graduates had been taught how to perform a DRE as a
      medical student, but 42% of medical students had performed fewer than five DREs
      before qualification. Their findings were rarely checked by a doctor. Of the
      students, 44% had never felt a clinically malignant prostate gland and 41% were
      'not at all confident' in their ability to give an opinion based on their
      findings on a DRE. House officers performed DRE regularly (53% >/= 50 DREs) but
      rarely received additional instruction, and exposure to pathology remained
      limited. House officers' findings on DRE were rarely confirmed by a more senior
      doctor. Most respondents had been taught how to perform male urethral
      catheterization as a medical student (92% of students, 89% of house officers) but
      48% of students had performed fewer than two catheterizations on qualification
      and 68% of house officers had received no additional instruction; however, 69% of
      house officers were 'very confident' in their ability to perform male urethral
      catheterization. CONCLUSIONS: The DRE is a critical skill in assessing the
      prostate; students conduct few DREs, lack confidence and are exposed to minimal
      pathology. Legitimate concerns over students carrying out intimate examinations
      may be mitigating against the acquisition of skills. Possible solutions are
      explored. House officers perform DREs regularly, but with no additional
      instruction they may continue to lack confidence. Students lack experience in
      male urethral catheterization and rarely receive postgraduate instruction. House
      officers' confidence in their ability to perform male urethral catheterization
      may be misplaced.

PMID- 10971266
TI  - Elevation of sensory thresholds in the prostatic urethra after microwave
      thermotherapy.
AB  - OBJECTIVES: To determine whether transurethral microwave thermotherapy (TUMT)
      affects the sensory threshold in the posterior urethra and whether such an effect
      influences urinary storage symptoms. PATIENTS AND METHODS: The sensory threshold
      was measured before and at 3 and 12 weeks after TUMT in 13 men with minor
      obstructive symptoms caused by benign prostatic hyperplasia. Sensations were
      evoked by electrical stimulation at different frequencies, using a bipolar ring
      electrode mounted on a urethral catheter. Changes in sensory thresholds were
      evaluated in the patients both as a group and individually. The patients were
      interviewed about their symptoms at each measurement. RESULTS: After TUMT, 12
      patients were satisfied and reported decreased irritative symptoms, primarily
      less frequent nocturnal micturition; two patients were cured of urgency
      incontinence. In 11 of the satisfied patients, and the unsuccessful patient,
      decreased urge accompanied increased sensory thresholds. Thresholds elevated by
      >/= 30% were correlated with decreased irritative symptoms. CONCLUSIONS: TUMT
      decreases sensitivity in the posterior urethra, which may alleviate storage
      symptoms.

PMID- 10971267
TI  - The clinical uroselectivity of alfuzosin is not significantly affected by the age
      of patients with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia.
AB  - OBJECTIVE: To assess the effect of the age of patients with benign prostatic
      hyperplasia (BPH) on the clinical uroselectivity of alfuzosin during general
      medical practice. PATIENTS AND METHODS: The present national, multicentre, open
      labelled, observational study involved 4018 Spanish outpatients with BPH, i.e.
      showing lower urinary tract symptoms (LUTS) suggestive of benign prostatic
      obstruction. The patients received sustained release (SR) alfuzosin, 5 mg twice
      daily, for 2 months. The primary efficacy criteria were symptomatic improvements,
      as assessed by the International Prostate Symptom Score (IPSS) and quality of
      life (QoL) index. Safety was assessed by monitoring cardiovascular data and
      adverse events. RESULTS: The patients were divided into four age groups, i.e. <
      56, 56-65, 66-75 and > 75 years. All groups of patients showed a mean IPSS
      decrease of 11-12 (55.8-65.4% from baseline) at the end of the study, while the
      QoL decreased by 2-3 points (55.6-63.6% from baseline). There were no relevant
      effects of age on the efficacy of the treatment. Moreover, alfuzosin was well
      tolerated independently of the age of the patient; 1.2% of the patients enrolled
      withdrew because of adverse events. The qualitative distribution of
      vasodilatory/nonvasodilatory adverse events was similar in all age groups. The
      incidence of asymptomatic orthostatic hypotension was low (0.58%) and not
      affected by the age of the patients. CONCLUSION: This study confirms that the
      clinical uro-selectivity of SR-alfuzosin, already described in ran-domized
      controlled studies, is not significantly affected in clinical practice by the age
      of the patients. This is considered particularly relevant to the characteristics
      of patients with BPH, as they are mostly elderly men.

PMID- 10971268
TI  - Combined sabal and urtica extract compared with finasteride in men with benign
      prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.
AB  - OBJECTIVE: To test the hypothesis that in patients with benign prostatic
      hyperplasia (BPH), the outcome of drug therapy with finasteride may be
      predictable from the baseline prostate volume and that positive clinical effects
      might be expected only in patients with prostate volumes of > 40 mL, using a
      subgroup analysis of results from a previously reported clinical trial of
      finasteride and phytotherapy. PATIENTS AND METHODS: A subgroup of 431 patients
      was analysed from a randomized, multicentre, double-blind clinical trial
      involving 543 patients with the early stages of BPH. Patients received a fixed
      combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root
      (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor
      finasteride. The patients assessed had valid ultrasonographic measurements and
      baseline prostate volumes of either </= 40 mL or > 40 mL. All 516 patients were
      included in the safety analysis. The results of the original trial showed
      equivalent efficacy for both treatments. RESULTS: The mean (SD) maximum urinary
      flow (the main outcome variable) increased (from baseline values) after 24 weeks
      by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There
      were no statistically significant group differences (P = 0.52). The subgroups
      with small prostates (</= 40 mL) showed similar improvements, with mean values of
      1.8 (5.2) mL/s with PRO 160/120 and 2.7 (7.4) mL/s with finasteride. The mean
      values for the subgroups with prostates of > 40 mL were similar, at 2.3 (6.1) and
      2. 2 (5.3) mL/s, respectively. There were improvements in the International
      Prostate Symptom Score in both treatment groups, with no statistically
      significant differences. The subgroup analysis showed slightly better results for
      voiding symptoms in the patients with prostates of > 40 mL, but there were also
      improvements in the subgroup with smaller prostates. The safety analysis showed
      that more patients in the finasteride group reported adverse events and also
      there were more adverse events in this group than in patients treated with PRO
      160/120. CONCLUSION: The present analysis showed that the efficacy of both PRO
      160/120 and finasteride was equivalent and unrelated to prostate volume. However,
      PRO 160/120 had better tolerability than finasteride.

PMID- 10971269
TI  - Epidemiology of prostatitis in Finnish men: a population-based cross-sectional
      study.
AB  - OBJECTIVE: To study the lifetime occurrence of prostatitis in Finnish men and
      their exposure to the disease. Subjects and methods A population-based cross
      sectional survey was conducted in the two most northerly provinces of Finland
      (Oulu and Lapland). Altogether, 2500 male residents aged 20-59 years were chosen
      at random to complete a questionnaire on prostatitis. The data were collected
      between June 1996 and October 1997. Replies were received from 1832 men, giving a
      response rate of 75%. RESULTS: The overall lifetime prevalence of prostatitis was
      14.2%. The risk of having or having had prostatitis increased with age, being 1.7
      times greater in men aged 40-49 years than in those aged 20-39 years, and 3.1
      times greater in those aged 50-59 years. The overall incidence was 37.8/10 000
      person years. More than a quarter of the 261 men who had or had had prostatitis
      symptoms (27%) suffered from them at least once a year, while 16% suffered from
      persistent symptoms; 63% of the men with prostatitis had their worst symptoms
      during the winter (November-March). Neither education nor profession had much
      influence on the occurrence of prostatitis, but divorced and single men had a
      lower risk than married men. Most patients felt they had not received enough
      information about the disease at their first visit to a general practitioner.
      CONCLUSIONS: The results of this survey showed that the occurrence of prostatitis
      symptoms in men living in northern Finland is higher than that reported in other
      parts of the world. This could be partly caused by the cold climate.

PMID- 10971270
TI  - Incidence of bone fracture in patients receiving luteinizing hormone-releasing
      hormone agonists for prostate cancer.
AB  - OBJECTIVE: To investigate the incidence of bone fractures in patients receiving
      luteinizing hormone-releasing hormone agonists (LHRH-a) for prostate cancer (in
      whom a continued low testosterone level after the long-term administration of
      these drugs reduces bone mineral density), and thus determine the risk of
      secondary osteoporosis. PATIENTS AND METHODS: Between 1994 and 1999, 218 patients
      (mean age 77.3 years) were treated for >/= 6 months with LHRH-a for prostate
      cancer; of these, 14 (6%) had a bone fracture during their treatment. Patients
      with fracture associated with motor vehicle accidents were excluded. The bone
      density in the third lumbar vertebra was meas-ured using quantitative computed
      tomography. Osteocalcin, 1,25-(OH)2 vitamin D, urinary type 1 collagen cross
      linked N-telopeptides (NTx), parathyroid hormone and calcitonin were measured as
      metabolic markers. RESULTS: The mean age of the patients with fracture was 78
      years; the mean (range) interval from the start of treatment to fracture was 28
      (11-46) months. There was no case of a bone fracture at the site of a metastasis
      from prostate cancer. The bone density was significantly lower in the patients
      with a fracture than in those without. Of the bone metabolic markers, NTx was
      higher in those with a fracture. CONCLUSION: There is a need to measure bone
      mineral density and bone metabolic markers periodically, and to evaluate
      secondary osteoporosis in patients receiving long-term LHRH-a for prostate
      cancer.

PMID- 10971271
TI  - Inactive free : total prostate specific antigen ratios in ejaculate from men with
      suspected and known prostate cancer, compared with young control men.
AB  - OBJECTIVE: To measure free : total prostate specific antigen (PSA) ratios in
      ejaculate from men with suspected and known prostate cancer, and in young control
      men, to determine if this ratio might be useful in discriminating benign from
      malignant prostatic conditions. Patients, subjects and methods Forty-seven men
      with prostate cancer (positive biopsies), 52 men with suspected prostate cancer
      but who had negative biopsies and 28 young men (< 30 years old) and with no
      family history of cancer, provided either a single ejaculate specimen (total 59)
      or multiple specimens (total 193) on subsequent occasions. Free and total PSA
      were measured using appropriate assays. All specimens were diluted in a PSA
      negative female serum pool. RESULTS: The median free : total PSA ratios were 0.76
      0.81 among the patient groups and control men, and there was no statistical
      difference between the groups. These data presumably only reflect the inactive
      component of free PSA, given that any alpha2-macroglobulin or alpha1
      antichymotrypsin in the assay serum diluent was likely to have bound the active
      free PSA component in these samples. Similar results were obtained from those
      providing single and multiple samples, suggesting that a single specimen is
      sufficient to reflect the seminal plasma free : total PSA ratio over that period.
      There was no relationship between seminal plasma free : total PSA ratio and age
      for the controls or the positive biopsy group, although there was a negative
      relationship (i.e. a decline with age) that almost reached significance in those
      with negative biopsies (P = 0.058, R2 = 0.07). CONCLUSIONS: This is the first
      report of free : total PSA ratios in the ejaculate of men with suspected and
      known prostate cancer compared with young control men. Although no significant
      changes were detected in the free : total PSA ratios in ejaculate, these results
      may be confounded by differences in ratios with age, as is the case for serum PSA
      or different molecular forms of PSA. Indeed, these data suggest that a large
      proportion of free PSA in seminal plasma may be inactive. Further studies are
      needed to determine the potential utility of measuring free : total PSA, or other
      candidate markers, in ejaculate to better discriminate benign from malignant
      prostate disease.

PMID- 10971272
TI  - The treatment of balanitis xerotica obliterans.

PMID- 10971273
TI  - Extracorporeal shock wave therapy in the management of Peyronie's disease:
      initial experience.
AB  - OBJECTIVE: To evaluate prospectively the efficacy of extracorporeal shock wave
      therapy (ESWT) as a conservative treatment for Peyronie's disease. PATIENTS AND
      METHODS: After obtaining ethical committee approval, 37 patients with Peyronie's
      disease were treated using ESWT. Before treatment the degree of angulation was
      assessed by artificially inducing an erection with a vacuum device. The severity
      of pain on erection was assessed using a visual analogue scale (0-5). Each
      patient was treated with a minimum of three sessions of ESWT (3000 shock waves at
      an energy density of 0.11-0.17 mJ/mm2) at 3-week intervals. The results were
      analysed using the Wilcoxon signed-rank test. RESULTS: Of the 37 patients, 34
      completed the protocol; the mean (range) duration of the disease was 19.43 (4-60)
      months and the mean follow-up 7.5 (5-11) months. Almost half (47%) of the
      patients reported an improvement in angulation, with a mean reduction of 29.3
      degrees (10 degrees -60 degrees ) (P < 0.001); 12 of the 20 (60%) patients with
      pain on erection reported immediate relief, the mean reduction being 2.3 (1-4) on
      the visual analogue scale (P < 0.001). There was only minimal bruising at the
      site of treatment and no major side-effects were reported. CONCLUSION: ESWT is an
      effective and safe treatment for Peyronie's disease; the long-term follow-up and
      results are awaited.

PMID- 10971274
TI  - Results from different patient populations using combined therapy with
      alprostadil and sildenafil: predictors of satisfaction.
AB  - OBJECTIVE: To evaluate the outcome of combined therapy (using intraurethral
      alprostadil and oral sildenafil) in private and clinic patients with erectile
      dysfunction, and thus assess predictors of satisfaction. PATIENTS AND METHODS: In
      all, 360 men were treated for erectile dysfunction using single and/or combined
      therapy, comprising 214 private-practice and 166 clinic patients. Responses were
      evaluated using the International Index for Erectile Function (IIEF)
      questionnaire before and after treatment. Serum testosterone levels, education
      and socio-economic status were also assessed. Group 1a consisted of 33 private
      patients and Group 1b of 24 clinic patients who tried the maximum dose of
      intraurethral alprostadil monotherapy initially, followed by the maximum dose of
      sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32
      private patients and group 2b of 31 clinic patients who tried the maximum dose of
      sildenafil monotherapy initially, followed by the maximum dose of alprostadil
      monotherapy, and were also dissatisfied. These two groups of 65 private and 55
      clinic patients then underwent combined therapy. RESULTS: The mean (SD) score for
      erectile function was 24.1 (2) for combined therapy (a 123% improvement), and
      19.8 (1. 8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and
      alprostadil monotherapies (P < 0.05 for both patient groups). The men also
      reported an improvement in their satisfaction with intercourse. However, at 18
      months, 60 of the 65 private patients but only 40 of the 55 clinic patients
      continued with combined therapy; thus, the discontinuation rate was three times
      greater among clinic than among private patients. Furthermore, the private
      patients had an overall improvement in the satisfaction score of 128%, compared
      with 51% for the clinic patients. CONCLUSION: Although there were no significant
      differences in erectile function improvement within the two satisfied combined
      therapy groups, the differences in overall satisfaction and long-term withdrawal
      rates suggests that other factors beside motivation must be involved for success,
      e.g. education, persistence, realistic expectations, and certain psychological
      factors. Combined therapy should be considered for those patients who have a
      suboptimal response to monotherapy and refuse or are not candidates for surgical
      options. Generally, those patients with a higher education, greater persistence
      and more realistic expectations were more satisfied with combined therapy.

PMID- 10971275
TI  - Failed vasectomy reversal: is a further attempt using microsurgery worthwhile?
AB  - OBJECTIVE: To determine, in failed vasectomy reversal, the usefulness of a
      revised anastomosis using microsurgery in achieving sperm in the ejaculate and
      fertility, and to relate the outcome to the site of the anastomosis, length of
      time from vasectomy, and presence or absence of sperm in the vas at surgery.
      PATIENTS AND METHODS: In a series of 28 patients with confirmed anastomotic
      obstruction undergoing vasectomy reversal (over a 10-year period), a
      microsurgical technique using an oblique end-to-end two-layer interrupted
      anastomosis with 10/0 Nylon was used to establish vasal continuity. Subsequent
      seminal analysis at 3-6 months and ensuing paternity were related to several
      variables. The results were compared with those obtained after 137 cases of
      primary microsurgical vasovasostomy. RESULTS: Sperm was restored to the ejaculate
      in 16 (57%) of the patients and successful fertilization was reported in nine
      (32%). The interval between vasectomy and reversal surgery was relevant to the
      outcome, with four out of four men having sperm in the ejaculate within 5 years
      and three achieving paternity. However, the fertility rate was still moderate
      after an interval of 6-10 years (two of six) and at > 10 years (four of 18). The
      presence of sperm in the ejaculate was related to whether or not sperm were found
      in the testicular end of the vas at operation, but absence did not preclude a
      successful outcome. The overall results were not significantly different from
      those after primary microsurgical reversal surgery. CONCLUSION: Microscopic
      vasovasostomy after previous obstructive failure provides the patient with a
      further reasonable chance of becoming fertile; although diminishing with time
      from vasectomy, even after a prolonged period there can be success. The absence
      of sperm at the time of vasovasostomy does not necessarily indicate failure, but
      in these cases the presence of thick creamy fluid in the vas predicts a poor
      outcome, and alternative methods of management should be considered. A
      microsurgical technique extending, if necessary, well into the convoluted part of
      the vas, is recommended. Microsurgical skills, relevant equipment and adequate
      time are required.

PMID- 10971276
TI  - Semen analysis after vasectomy: when and how many?
AB  - OBJECTIVE: To assess patient compliance for semen analysis after vasectomy, and
      to determine the timing and number of semen analyses required to confirm
      sterility. PATIENTS AND METHODS: The study included 1321 men who underwent
      vasectomy between October 1995 and June 1998. They were followed up in two
      groups; in group 1 (one-test method) 961 consecutive patients were asked to
      provide a semen sample for analysis 4 months after vasectomy. Sterility was
      defined as the absence of sperm in one sample. If sperm were present in the
      sample, the test was repeated at monthly intervals until there were no sperm. In
      group 2 (two-test method) 360 consecutive patients were advised to provide semen
      samples 3 and 4 months after vasectomy. The absence of sperm in two consecutive
      samples was defined as the criterion to declare the man azoospermic. The presence
      of sperm in one sample required further samples every month until two consecutive
      azoospermic samples were produced. RESULTS: In group 1, 810 patients provided
      semen samples, of which 783 (97%) had no sperm and the men were thus declared
      azoospermic. The remaining 27 (3%) samples contained sperm; six men withdrew from
      follow-up at various times but 21 patients produced a negative sample at some
      time within 7 months and were declared azoospermic. At the end of the follow-up,
      804 (84%) patients had been declared azoospermic. In group 2, 294 (82%) patients
      provided a semen sample after 3 months but only 259 (72%) did so after 4 months.
      Of the patients providing the first sample, 287 (98%) were azoospermic, and after
      the second 252 (97%) were azoospermic. At the end of the follow-up 255 (71%)
      patients were declared azoospermic. There was no reported paternity in any of the
      men. CONCLUSION: These results suggest that compliance was better in group 1;
      when the patients in group 2 were asked to provide a second sample the compliance
      decreased significantly. The percentage of patients producing an azoospermic
      sample was similar for semen provided after 3 and 4 months. Thus, provided that
      the patient is adequately warned about the risk of failure of the vasectomy at
      any time during his life, a single semen analysis after 3 months is sufficient
      grounds for discontinuing other contraceptive precautions.

PMID- 10971277
TI  - Testicular microlithiasis in a UK population: its incidence, associations and
      follow-up.
AB  - OBJECTIVES: To determine the incidence of testicular microlithiasis in men
      presenting for testicular ultrasonography, to identify any associated pathology
      (with particular reference to testicular neoplasia) and to report the follow-up
      of those patients in whom testicular microlithiasis was identified. PATIENTS AND
      METHODS: In this retrospective study, the results of all testicular
      ultrasonography undertaken between July 1995 and March 1998 in a district general
      hospital were reviewed. The records of all patients diagnosed
      ultrasonographically to have testicular microlithiasis were retrieved and the
      pathology database was accessed for all testicular tumours diagnosed in the same
      period. RESULTS: During the study period 2215 scans were taken; 34 cases of
      testicular microlithiasis were identified, giving an incidence of 1.4%. Thirty
      one testicular tumours were removed during the same period. Of the 34 cases with
      testicular microlithiasis, five had histologically confirmed testicular tumours
      (15%). The incidence of testicular tumours in the scans showing no microlithiasis
      was 26 in 2181 (1.1%). The differential incidence of tumours in the two groups is
      statistically significant (P < 0.001, chi-square analysis). Patients with
      testicular microlithiasis but no tumour were followed up for a median (range) of
      41 (19-54) months; no interval tumours have developed to date. CONCLUSION: This
      study confirms an incidence of testicular microlithiasis comparable with that in
      other reported series, albeit in a selected population. There was a strong
      association between testicular microlithiasis and testicular tumours. Whether
      this is a causal relationship has yet to be determined. Careful clinical and
      ultrasonographic follow-up of these patients is therefore recommended until the
      significance of testicular microlithiasis is clear.

PMID- 10971278
TI  - Diagnostic delay and risk of relapse in patients with stage I nonseminomatous
      germ cell tumour followed on active surveillance.
AB  - OBJECTIVE: To determine whether delayed diagnosis affects the outcome of patients
      with stage I nonseminomatous germ cell tumour (NSGCT) followed by a policy of
      'active surveillance'. PATIENTS AND METHODS: A series of 185 consecutive patients
      with either low-risk (no vascular invasion) or unknown risk stage I NSGCT
      referred to Mount Vernon Hospital between 1983 and 1998 were analysed
      retrospectively for the type and duration of symptoms before orchidectomy, time
      to relapse, and for site and stage of relapse. RESULTS: Twenty-six patients (14%)
      relapsed within a medium follow-up of 98 months. The median (range) time to
      relapse was 4 (1-14) months. All patients were effectively salvaged with
      chemotherapy and in some by surgery. The median duration of symptoms before
      orchidectomy for those patients relapsing was 2 months, and not significantly
      different from those who did not relapse. CONCLUSIONS: In patients with stage I
      NSGCT the duration of symptoms before diagnosis did not influence the probability
      of relapse.

PMID- 10971279
TI  - The prevalence of varicocele and varicocele-related testicular atrophy in Turkish
      children and adolescents.
AB  - OBJECTIVE: To determine the prevalence and site of varicocele and varicocele
      related testicular atrophy in children and adolescents. PATIENTS AND METHODS: The
      study included 4052 boys aged of 2-19 years, divided into four age groups; the
      findings of a physical examination, any testicular atrophy and testicular volume
      were recorded. RESULTS: Varicocele was detected in 293 (7.2%) of the 4052 boys;
      the prevalence was 0.79% in those aged 2-6 years, 0.96% at 7-10 years, 7.8% at 11
      14 years and 14.1% at 15-19 years. The prevalence was 0.92% in 1232 children aged
      2-10 years and 11.0% in 2531 adolescents aged 11-19 years (P < 0.001). The
      prevalence increased significantly at age 13 years (P < 0.005). The varicocele
      was unilateral in 263 of the 293 (89.7%) boys with varicocele; of these, one
      (0.38%) was on the right and the others on the left side. Varicoceles were
      bilateral in 30 of 279 boys (10.8%) aged 11-19 years but none were detected in
      those aged < 11 years. Varicocele-related testicular atrophy was not present in
      those aged < 11 years, but seven boys (7.3%) aged 11-14 years and 17 (9.3%) aged
      15-19 years had testicular atrophy. The difference in prevalence between the last
      two age groups with atrophy was not significant. CONCLUSION: These findings
      support the view that varicocele is a progressive disease and that the prevalence
      of varicocele and testicular atrophy increases with the puberty.

PMID- 10971281
TI  - A 14-year follow-up of conservative treatment for vesico-ureteric reflux.
AB  - OBJECTIVE: To determine renal function in patients with vesico-ureteric reflux
      (VUR) during 14 years of conservative treatment (no surgery). PATIENTS AND
      METHODS: Sixty patients with VUR were consecutively included between 1981 and
      1982. The degree of VUR was determined by conventional voiding cysto
      uretherography (VCUG) after 3 months of prophylactic antibiotics. The VUR was
      grade I-IV, with grades III and IV characterized as high-grade VUR. In all
      patients, any urinary tract infections and bladder-urethral dysfunction were
      treated. Renal function and reflux were monitored by renal and bladder
      scintigraphy using 123I-hippuran and the glomerular filtration rate (GFR) was
      determined using the plasma clearance of 51Cr-ethylaminediamine tetra-acetic
      acid. RESULTS: Of the 60 patients who entered the study, 51 were followed for a
      mean of 13.7 years; nine patients were lost to follow-up. None of the patients
      underwent antireflux surgery. All patients were in good health and normotensive
      (except two with borderline hypertension). Of the 51 patients 21 had low-grade,
      21 unilateral high-grade and nine bilateral high-grade reflux. In those with low
      grade reflux both the mean renal split function on the most refluxing kidney and
      the GFR remained stable during the whole monitoring period. Eighteen patients who
      had a persistent reduction in renal split function or initially had had a
      significantly reduced functional share to the most refluxing kidney had their GFR
      re-assessed in adolescence. However, the body surface-corrected GFR remained
      constant. Total GFR and single kidney GFR increased significantly. CONCLUSION: A
      conservative treatment regimen in patients with VUR can ensure stable kidney
      function, although kidneys with a lower renal function at referral seem to have
      an impaired functional growth potential.

PMID- 10971280
TI  - Angiotensin II in child urinary bladder: functional and autoradiographic studies.
AB  - OBJECTIVES: To investigate the receptors for angiotensin II (AII, reported to be
      a potent contractile agent in human urinary bladder), using functional and
      autoradiographic techniques in child and adult bladder specimens. Materials and
      methods Bladder specimens were obtained from 61 children (aged 4 months to 12
      years) undergoing ureteric reimplantation for vesico-ureteric reflux, and from 10
      adults undergoing cystectomy. After overnight storage, the mucosa was removed and
      isometric contractions obtained from detrusor muscle strips in the presence of
      phosphoramidon (10 micromol/L). Only one concentration of AII was added to each
      preparation because of tachyphylaxis. The response to KCl (124 mmol/L) was 43% of
      that to carbachol (100 micromol/L). Sections of child bladder were radio-labelled
      with the ligand [125I]Sar1,Ile8-AII and binding sites visualized using emulsion
      autoradio- graphy. RESULTS: The potency of AII was similar in child and adult
      detrusor strips, with mean (SEM) pD2 values of 6.9 (1.0) (n = 25) and 6.7 (0.2)
      (n = 9) respectively, and the maximum responses (to 10 micromol/L AII) rather low
      (39% and 49%, respectively, P > 0.05), compared with carbachol (100 micromol/L).
      There were no age- or gender-related differences. Responses to AII in strips from
      children under 3 years old were antagonized by the AT1 receptor antagonist
      losartan (1 micromol/L) but not by the AT2 receptor antagonist PD 123319 (1
      micromol/L), indicating interaction with the AT1 receptor. Sections of child
      bladder radiolabelled with [125I]Sar1,Ile8-AII showed moderate specific binding
      over detrusor muscle and arterioles, with denser specific binding over
      subepithelial blood vessels. Specific binding was inhibited by co-incubation with
      losartan (10 micromol/L) but not with PD 123319 (10 micromol/L). CONCLUSION: AII
      was a weak contractile agent of detrusor strips, with no significant differences
      in potency between child and adult bladder samples. These data show the presence
      of functional AT1 but not AT2 receptors in child detrusor smooth muscle.

PMID- 10971282
TI  - The management of children with complete ureteric duplication: selective use of
      uretero-ureterostomy as a primary and salvage procedure.
AB  - OBJECTIVE: To determine the optimum management of duplex urinary tracts with
      refluxing or obstructed units. PATIENTS AND METHODS: Sixty-three children (19
      boys and 44 girls) with complete duplex-system anomalies (84 duplex system units)
      who underwent corrective surgery by one surgeon (H.C.) between March 1983 and
      June 1997 were reviewed, analysing their diagnosis and treatment. RESULTS: Most
      children had presented with urinary tract infection; a ureterocele was found in
      26 renal units, reflux in 12 and a combined anomaly in 18. Ectopic insertion of
      the ureter causing incontinence was found in six and ureteric obstruction in nine
      ureteric units. Patients were managed so that whenever possible, functional renal
      tissue was preserved; thus surgical strategies were basically staged,
      conservative, and planned preoperatively on the basis of renal function. Initial
      surgery was undertaken in 71 units (all patients; ureterocele incision in 12,
      upper pole nephrectomy in 30, ureteric reimplantation in 14, uretero-ureterostomy
      in 13 and others in two). The median (range) follow-up was 7.6 (2.1-16) years.
      Secondary procedures were undertaken in 24 units (34%); ureterocele incision (11
      of 12 units) was the most common procedure of additional surgery, followed by
      ureteric reimplantation (six of 27 units), upper pole nephrectomy (eight of 37
      units) and uretero-ureterostomy (two of 18 units). CONCLUSIONS: Uretero
      ureterostomy was the most successful nephron-sparing additional operation. When
      the upper pole is salvageable, uretero-ureterostomy may be the preferred
      alternative for managing complete duplex system anomalies.

PMID- 10971283
TI  - Combined bladder neck, urethral and penile reconstruction in boys with the
      exstrophy-epispadias complex.
AB  - OBJECTIVE: To describe a one-stage combined bladder neck, urethral and penile
      reconstruction for achieving urinary continence and creating a penis with good
      cosmesis and function in boys with the exstrophy-epispadias complex. PATIENTS AND
      METHODS: Seventy-three boys underwent the combined procedure, including 36 after
      classic bladder exstrophy closure and 37 with epispadias. All were completely
      incontinent at the time of combined reconstruction. The bladder capacity just
      before surgery was 70-180 mL and was greater in those with epispadias. The boys
      were 2.5-11 years old, with those in the exstrophy group being slightly older.
      RESULTS: Thirty-three boys (89%) with epispadias were completely continent during
      the day but 15 had episodes of nocturnal enuresis. Of boys with classic
      exstrophy, 27 (75%) were continent during the day but nine had occasional
      nocturnal enuresis. Eleven boys required intermittent catheterization, which they
      found easy to perform. In seven boys (10%) a urethrocutaneous fistula or urethral
      stricture developed. CONCLUSIONS: Combined bladder neck, urethral and penile
      reconstruction can be carried out as a one-stage procedure in selected patients
      with adequate bladder capacity. Reconstruction of the whole length of the urethra
      facilitates intermittent catheterization.

PMID- 10971284
TI  - Congenital megaprepuce: an emerging condition--how to recognize and treat it.
AB  - OBJECTIVE: To highlight the clinical presentation, pathological anatomy and
      surgical management of an emerging condition, the congenital megaprepuce (CM).
      PATIENTS AND METHODS: All patients with CM treated at Southampton between 1994
      and 1998 were reviewed retrospectively; 20 patients underwent surgery (mean age
      at operation 16 months, range 6-43). Surgical correction developed over this
      period and variations on a basic technique are now used, depending on the precise
      pathological anatomy. These techniques are described and illustrated. Cosmetic
      and functional success, and parental satisfaction, were assessed by a review of
      the case-notes. RESULTS: After a follow-up of >/= 6 months, the cosmetic and
      functional outcome was very successful, with the parents of 19 of the 20 patients
      satisfied. Five patients underwent re-operation, all requiring excision of
      redundant penile skin. CONCLUSIONS: CM is a striking condition which cannot be
      easily missed or hidden; we propose that it is a newly emerging and distinct
      condition which should not be confused with a buried, concealed, webbed, trapped
      or micropenis. Early surgical correction is recommended and circumcision should
      be avoided.

PMID- 10971285
TI  - The buried penis--an anatomical approach.

PMID- 10971286
TI  - Buried penis: surgical correction using liposuction and realignment of skin.

PMID- 10971287
TI  - The actions of metabolic inhibition on human detrusor smooth muscle contractility
      from stable and unstable bladders.
AB  - OBJECTIVES: To determine the important cellular site(s) of action of a brief
      exposure to NaCN (chosen to reduce mitochondrial respiration and hence mimic
      cellular hypoxia) on the mechanical properties and regulation of intracellular
      [Ca2+] in human detrusor smooth muscle. Using muscle samples obtained from
      patients with stable and unstable bladders, to determine whether the unstable
      bladder is associated with changes in the functional properties of detrusor
      muscle under these circumstances. Materials and methods Experiments were
      conducted in vitro on muscle strips or isolated cells. Isometric tension was
      recorded in muscle strips during electrical stimulation or exposure to agonists.
      Intracellular [Ca2+] and [H+] were measured by epifluorescence microscopy, and
      cell autofluorescence measured as an index of mitochondrial function. RESULTS:
      There were no differences in the responses to electrical stimulation and varying
      concentrations of carbachol in muscle strips from stable and unstable bladders.
      NaCN (2 mmol/L) reduced the contraction induced by carbachol (10 micromol/L) by a
      mean (SD) of 43 (16)% and 56 (15)% in the two groups; the reduction in the
      unstable was significantly less than in the stable group. NaCN similarly reduced
      the response to 10 mmol/L caffeine, but had no effect on the KCl-induced
      contraction. NaCN significantly increased the resting sarcoplasmic [Ca2+] and
      attenuated the calcium transients evoked by carbachol and caffeine, but again had
      no effect on the KCl-induced transient. The reduction of the carbachol calcium
      transient was also less in cells from unstable bladders than in those from stable
      bladders. There was no effect of NaCN on intracellular pH, except for a brief,
      transient alkalosis. CONCLUSIONS: NaCN reduces both the contraction and Ca
      transient to carbachol by reducing Ca2+ accumulation by intracellular stores,
      because the carbachol- and caffeine-evoked responses were similar. Any effect on
      transmembrane Ca2+ flux was minimal because there was no effect on KCl-induced
      responses. The greater resilience of tissue from unstable bladders to acute
      cellular hypoxia may reflect some adaptation acquired in vivo.

PMID- 10971288
TI  - The contribution of cholinergic detrusor excitation in a pig model of bladder
      hypocompliance.
AB  - OBJECTIVE: To investigate the role of cholinergic excitation in mediating changes
      in detrusor compliance (manifested on conventional cystometry as an incremental
      rise in detrusor pressure as bladder volume increases) under conditions of
      propofol-sedation in the pig. Materials and methods Consecutive cystometrograms
      (CMGs) were obtained from eight female Large White pigs at a bladder filling rate
      of 50 mL/min. The first CMG was obtained while the pig was awake and unsedated.
      Two subsequent CMGs were obtained after light to moderate sedation with propofol
      (2-8 mg/kg/h) before and after the administration of intravenous atropine (0.02
      mg/kg). RESULTS: All bladders were highly compliant over the volumes instilled
      (before sedation) with a maximum pressure during the filling phase of 0.9 cmH2O
      and a compliance of 943 mL/cmH2O. After sedation with propofol, the maximum
      pressure during the filling phase increased to 14 cmH2O with a compliance of 69
      mL/cmH2O. Atropine antagonized this change in compliance; after sedation and
      atropine, the maximum pressure during the filling phase decreased to 4 cmH2O (P <
      0.05) and the compliance increased to 337 mL/cmH2O (P < 0.05). CONCLUSION: The
      decrease in compliance seen in the pig bladder after sedation with propofol is
      mediated via muscarinic excitation. This probably occurs as a result of low-level
      tonic release of acetylcholine by the efferent parasympathetic nerves. The
      existence of such efferent excitatory activity during the storage phase in the
      overactive human bladder might explain the efficacy of bladder-selective
      muscarinic antagonists in a proportion of patients with detrusor hyper-reflexia
      and instability.

PMID- 10971289
TI  - Inhibitory effect of calcium phosphate-associated proteins on calcium oxalate
      crystallization: alpha2-HS-glycoprotein, prothrombin-F1 and osteopontin.
AB  - OBJECTIVE: To analyse urinary calcium phosphate- associated proteins and assess
      their inhibitory effects on calcium oxalate crystallization. Materials and
      methods Urine samples were collected over 24 h from five healthy men and calcium
      phosphate crystallization induced with NaOH solution. The bound proteins were
      separated on a cellulose column. To examine the effect of urinary calcium
      phosphate-associated proteins on calcium oxalate crystallization, 60 L of urine
      was collected from the healthy men. The effect of the separated fractions was
      studied in a mixed suspension/mixed product removal system. RESULTS: The
      separated proteins were identified as alpha2-HS-glycoprotein, prothrombin
      fragment 1 and osteopontin. Prothrombin fragment 1 and osteopontin strongly
      inhibited the growth of calcium oxalate crystals in artificial urine. CONCLUSION:
      alpha2-HS-glycoprotein, prothrombin fragment 1 and osteopontin selectively bound
      with calcium phosphate crystals in urine. Prothrombin fragment 1 and osteopontin
      in urine may strongly influence stone formation.

PMID- 10971291
TI  - The role of the activated form of matrix metalloproteinase-2 in urothelial
      cancer.
AB  - OBJECTIVE: To investigate the expression of matrix metalloproteinase-2 (MMP-2,
      reportedly associated with cancer cell invasion and metastasis in many human
      cancers) in urothelial tumours and thus define its role in this disease.
      Materials and methods The expression of both the activated form of MMP-2 and
      total MMP-2 (activated + latent form) was measured using gelatine zymography in
      tissue obtained surgically from 61 patients with urothelial cancer. The
      correlation between the level of the activated form of MMP-2 and clinical and
      histological variables was assessed. RESULTS: The expression of activated and
      total MMP-2 were significantly higher in invasive tumour tissue and both levels
      were correlated with histological grade. In particular, the level of activated
      MMP-2 was more closely correlated than that of total MMP-2 in invasive tumour
      tissue. Moreover, high levels of activated MMP-2 were strongly associated with
      shorter disease-specific survival (P = 0.0016). CONCLUSION: These findings
      suggest that activated MMP-2 plays a significant role in invasion of urothelial
      cancer and that the level of activated MMP-2 expression is a useful prognostic
      indicator.

PMID- 10971290
TI  - The role of reactive oxygen species in testicular dysfunction associated with
      varicocele.
AB  - OBJECTIVE: To determine the level of malondialdehyde (MDA), an indirect indicator
      of lipid peroxidation-induced injury by reactive oxygen species, in testicular
      biopsy specimens from infertile patients with and without varicocele. PATIENTS
      AND METHODS: Levels of MDA were measured in the testicular biopsy specimens from
      25 infertile men (15 with varicocele, mean age 30.0 years, SD 5.7, range 23-45,
      and 10 without, mean age 28.7 years, SD 4.2, range 21-34). All patients were
      evaluated by a detailed history, physical examination, semen analysis (at least
      twice), serum follicle-stimulating hormone and free testosterone levels,
      testicular biopsy and contact imprint. Scrotal colour Doppler ultrasonography was
      used to confirm suspected varicocele. The level of MDA in testicular biopsy
      specimens was measured using the thiobarbituric acid test and the results
      expressed per unit tissue weight. RESULTS: As a causal factor for infertility,
      varicocele was identified in 15 men (60%), testicular failure in four (16%),
      idiopathic infertility in four (16%) and obstruction in two (8%). Of the 15
      patients with varicocele, eight had bilateral varicocele and it was subclinical
      in three; the varicocele was grade I in four, grade II in six and grade III in
      two. The mean (SD) MDA level in the men with a subclinical varicocele was 15.7
      (3.1) pmol/mg tissue, while in those with grade I-III varicocele it was 32.9
      (12.25), 37.1 (12.25) and 86.9 (2.89) pmol/mg tissue, respectively. The levels in
      patients with grade III varicocele were significantly greater than in the other
      groups (P < 0.05). The mean MDA level in patients with or without varicocele was
      38.3 (22.92) and 33.5 (18.93) pmol/mg tissue, respectively (P > 0.05).
      CONCLUSION: These results suggest that increasing levels of MDA are associated
      with higher grades of varicocele and support a possible rationale for controlled
      trials in infertile men with varicocele.

PMID- 10971292
TI  - Xanthogranulomatous pyelonephritis and renal malignancy: unusual fellows in the
      renal bed.

PMID- 10971293
TI  - Splenogonadal fusion associated with primary male infertility.

PMID- 10971294
TI  - Is the measurement of serum testosterone routinely indicated in men with erectile
      dysfunction?

PMID- 10971295
TI  - Apoptosis in the erectile tissues of diabetic and healthy rats.

PMID- 10971296
TI  - The pressure-flow plot in the evaluation of female incontinence.

PMID- 10971297
TI  - Gastroureteroplasty in a woman with bilateral ureteric strictures after pelvic
      radiotherapy.

PMID- 10971298
TI  - Urethral strictures and their surgical treatment.

PMID- 10971299
TI  - The pharmacology of paediatric incontinence.

PMID- 10971300
TI  - The clinical impact of different assays for prostate specific antigen.

PMID- 10971301
TI  - Apoptosis and its relevance to urologists.

PMID- 10971302
TI  - The effects of lamotrigine on the pharmacokinetics of lithium.
AB  - AIMS: The treatment of bipolar disorder often includes use of multiple drug
      therapies. Lithium is one of the most commonly used treatments, but has a narrow
      therapeutic window. Lamotrigine, an established antiepileptic drug, is emerging
      as a potentially important new therapy in the treatment of bipolar disorder. The
      objective of this two-treatment crossover study was to determine whether
      lamotrigine affects lithium pharmacokinetics. METHODS: Twenty healthy adult men
      completed the study. Subjects took 2 g lithium gluconate anhydrous every 12 h in
      the morning and evening for 5 days and in the morning of day 6, with or without
      100 mg lamotrigine once daily in the morning for 6 days. Blood and urine samples
      were collected on day 6 of both treatments to characterize the pharmacokinetics
      of lithium using noncompartmental methods. RESULTS: The geometric least-square
      mean ratio for renal clearance of lithium between the combination treatment and
      lithium alone treatment was 0.93 (95% confidence interval 0.85-1.02). Both
      treatments were well tolerated. CONCLUSIONS: Lamotrigine does not cause
      significant change in the pharmacokinetics of lithium.

PMID- 10971303
TI  - Steady-state pharmacokinetics of lithium in healthy volunteers receiving
      concomitant meloxicam.
AB  - AIMS: This open, controlled study investigated the effect of concomitant 15 mg
      oral meloxicam on the pharmacokinetics of lithium in healthy male volunteers.
      METHODS: On days 1-14 lithium was coadministered with meloxicam to 16 volunteers;
      on days 10-14 lithium was administered in individualized dosage regimes to
      achieve stable lithium plasma concentrations in the lower therapeutic range of
      0.3-0.7 mmol l(-1). A 12 h steady-state concentration profile for lithium was
      obtained at day 14, after which meloxicam was withdrawn. The lithium dose
      remained unchanged from day 15 to day 22, at which time a second lithium
      concentration profile was determined. RESULTS: Lithium and meloxicam were well
      tolerated throughout the study and all 16 volunteers completed the study. Lithium
      predose concentrations (Cpre,ss) and area under the curve (AUCss) values both
      increased by 21% (paired t-test P = 0.0002; 90% confidence intervals for
      test/reference ratios: 113-130% and 115-128%, respectively) when lithium was
      coadministered with meloxicam compared with values obtained for lithium alone.
      The geometric mean lithium Cpre,ss was 0.65 mmol l(-1) when coadministered with
      meloxicam and 0.54 mmol l(-1) for lithium alone. Lithium Cmax,ss values were
      increased by 16% by coadministration of meloxicam, from 0.97 mmol l(-1) to 1.12
      mmol l(-1). The total plasma clearance of lithium was lower with concomitant
      meloxicam administration (82.5% of value for lithium alone). CONCLUSIONS:
      Meloxicam (15 mg) moderately increased the plasma concentration of lithium in
      healthy volunteers, but by a magnitude thought to be of low clinical relevance.
      Nevertheless, lithium plasma concentrations should be closely monitored in
      patients receiving concomitant meloxicam and lithium therapy.

PMID- 10971304
TI  - Muscular and cardiorespiratory effects of pseudoephedrine in human athletes.
AB  - AIMS: Pseudoephedrine (PSE) is a readily available over-the-counter nasal
      decongestant which is structurally similar to amphetamine and is included on the
      International Olympic Committee's list of banned substances. However to date,
      little research has supported its putative ergogenic effect. This study
      investigated whether a 180 mg dose of PSE ingested 45 min prior to exercise
      enhanced short-term maximal exercise performance and/or altered related
      physiological variables. METHODS: A randomised, double-blind, crossover study in
      22 healthy male athletes. RESULTS: Maximum torque (mean +/- s.d., n = 22)
      produced in an isometric knee extension exercise was 321.1+/-62.0 Nm (PSE) and
      295.7+/-72.4 Nm (placebo), and peak power obtained on the 'all-out' 30 s cycle
      test was 1262.5+/-48.5 W (PSE) and 1228.4+/-47.1 W (placebo) (P<0.01, P<0.03,
      respectively). Subjects were estimated to be producing 96.9+/-2.4% of their
      maximal possible isometric leg extension force after PSE ingestion, but only
      95.3+/-2.4% when PSE was not ingested. Bench press tasks and total work during
      the cycle test were not affected by the ingestion of PSE. Lung function was
      altered following ingestion of PSE (P<0.05) with FEV1 and FVC significantly
      increased (P<0.02, P<0.01, respectively) although the FEV1/FVC ratio was not
      altered. Heart rate was significantly elevated by the ingestion of PSE
      immediately following the 30 s cycle sprint (P<0.01) however, lactate
      concentration was not altered by the ingestion of PSE. CONCLUSIONS: The
      administration of a 180 mg dose of PSE increased maximum torque, produced in an
      isometric knee extension and produced an improvement in peak power during maximal
      cycle performance, as well as improving lung function.

PMID- 10971305
TI  - A double-blind placebo-controlled study of the effectiveness and tolerability of
      oral stevioside in human hypertension.
AB  - AIMS: Stevioside is a natural plant glycoside isolated from the plant Stevia
      rebaudiana which has been commercialized as a sweetener in Japan for more than 20
      years. Previous animal studies have shown that stevioside has an antihypertensive
      effect. This study was to designed to evaluate the effect of stevioside in human
      hypertension. METHODS: A multicentre, randomized, double-blind, placebo
      controlled study was undertaken. This study group consisted of 106 Chinese
      hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and
      ages ranging from 28 to 75 years with 60 subjects (men 34, women 26; mean +/-
      s.d., 54.1+/-3.8 years) allocated to active treatment and 46 (men 19, women 27;
      mean +/- s.d., 53.7+/-4.1 years) to placebo treatment. Each subject was given
      capsules containing stevioside (250 mg) or placebo thrice daily and followed-up
      at monthly intervals for 1 year. RESULTS: After 3 months, the systolic and
      diastolic blood pressure of the stevioside group decreased significantly
      (systolic: 166.0+/-9.4-152.6+/-6.8 mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6
      mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry
      parameters including lipid and glucose showed no significant changes. No
      significant adverse effect was observed and quality of life assessment showed no
      deterioration. CONCLUSIONS: This study shows that oral stevioside is a well
      tolerated and effective modality that may be considered as an alternative or
      supplementary therapy for patients with hypertension.

PMID- 10971306
TI  - Heparin-mediated selective release of hepatocyte growth factor in humans.
AB  - AIMS: The aim of this investigation was to compare the effects of standard (S)
      with low molecular weight (LMW) heparin on circulating levels of heparin-binding
      growth factors (HBGF), known to have angiogenic properties in humans. METHODS: In
      two consecutive trials 18 healthy male volunteers were studied on three separate
      occasions, following a placebo-controlled crossover design. Subjects were
      randomised to receive either S-heparin or LMW heparin or placebo. Heparins were
      administered either by intravenous (i.v.) or subcutaneous (s.c.) injection and
      saline placebo by i.v. injection. Serum concentrations of hepatocyte growth
      factor (HGF), vascular endothelial cell growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) were measured before and up to 24 h after injection.
      RESULTS: Administration of i.v. S-or LMW-heparin (50 IU kg(-1) resulted in rapid,
      highly significant (47 fold for S, 30.9 fold for LMW) increases in HGF serum
      values, reaching maxima of 10.51+/-1.65 ng ml(-1) (S) and 8.28+/-1.04 ng ml(-1)
      (LMW), respectively, 10 min after drug application. S.c. injection of S-heparin
      or LMW heparin resulted in 4.1 and 5.4 fold increases in HGF serum values,
      respectively. Both agents showed no effects on circulating VEGF or bFGF levels,
      independent of the route of administration. CONCLUSIONS: Circulating HGF levels
      were selectively increased in response to pharmacological doses of two, widely
      used heparin preparations. This may, in part, explain some of the biological
      effects of heparin separate from its anticoagulant properties. By this mechanism,
      the systemic administration of heparin may facilitate collateral vessel formation
      in various clinical settings of tissue ischaemia.

PMID- 10971307
TI  - Influence of asimadoline, a new kappa-opioid receptor agonist, on tubular water
      absorption and vasopressin secretion in man.
AB  - AIMS: The purpose of the study was to investigate the effects of asimadoline, a
      new kappa-opioid agonist, on renal function and on hormones related to body fluid
      balance as well as its tolerability in healthy subjects. METHODS: In a placebo
      controlled, randomised, double-blind crossover design we studied the effects of
      single oral doses of 1, 5, and 10 mg of asimadoline, in 24 healthy volunteers.
      Two hour control urine collections were followed by 2 h postdose urine
      collections and subsequently 2.5% saline was given i.v. at a rate of 0.3 ml min(
      1) kg(-1) during another 2 h urine collection. Blood was obtained hourly.
      Arginine-vasopressin (AVP), atrial natriuretic peptide (alpha-hANP), endothelin
      (ET-1) and cAMP were determined by r.i.a. or ELISA. RESULTS: GC-MS measurements
      revealed Cmax values of asimadoline in plasma ranging from 18 ng ml(-1) at the 1
      mg dose, 91 ng ml(-1) at the 5 mg dose, to 214 ng ml(-1) at the 10 mg dose after
      an average of 1.1-1.4 h. Without effects on blood pressure, heart rate, GFR or
      urine electrolyte excretion, urine volume increased after 1-2 h after
      administration of 5 and 10 mg asimadoline from 3.3+/-1.3 to 5.6+/-1.4 (P<0.05)
      and from 3.2 +/-1.6 to 5.5+/-2.2 ml min(-1) (P<0.01), respectively. CH2O rose
      from 0.2+/-1.5 to 2.0+/-1.6 (P<0.05) and from 0.6+/-1.6 to 3.0+/-1.6 ml min(-1)
      (P<0.01). Urinary excretion of AVP was suppressed only with the 10 mg dose from
      46+/-23 to 25+/-15 fmol min(-1) (P<0.05) without and from 410+/-206 to 181+/-125
      fmol min(-1) (P<0.05) with stimulation by 2.5% saline. Plasma AVP was suppressed
      only by the 10 mg dose of asimadoline in six of eight subjects during the 2.5%
      saline infusion. Changes in the alpha-hANP or ET-1 systems were not affected by
      asimadoline. CONCLUSIONS: Asimadoline is diuretic in man after single doses of 5
      or 10 mg probably through a direct effect at the renal tubular level. Suppression
      of AVP secretion was observed only at the highest dose level of 10 mg of
      asimadoline.

PMID- 10971309
TI  - The pharmacokinetics and pharmacodynamics of oral dofetilide after twice daily
      and three times daily dosing.
AB  - AIMS: The pharmacokinetics and pharmacodynamics of oral dofetilide, a novel,
      class III antiarrhythmic drug, were assessed during administration either twice
      or three times daily. METHODS: Dofetilide was administered orally to three groups
      of healthy subjects in daily doses of 1000 microg (n = 8), 1500 microg (n = 8),
      or 2500 microg (n = 9) as twice daily and three times daily treatment regimens,
      with the two regimens assigned randomly as a two-way crossover for each subject
      and separated by at least a 6 day washout period. RESULTS: Pharmacokinetic
      analysis indicated a rise in plasma dofetilide concentrations until steady state
      was attained on day 3. Ctrough had a linear dependence on dose for both the twice
      daily and three times daily dosing regimens. The maximum concentration attained
      (Cmax) and the area under the concentration vs time curve (AUC(0,tau) increased
      linearly with dose for each dosing regimen on both days 1 and 5 of dosing. Cmax
      occurred at 2 h. Pharmacodynamic measurements showed that the QTc interval
      increased in a dose-dependent manner and that the time to maximum QTc was 2 h
      after dosing. A linear relationship was determined between plasma dofetilide
      concentration and the prolongation of the QTc interval. The slope of this line
      was significantly greater on day 1 (ranging from 12.9 to 14.2 ms/ng ml-1) than on
      day 5 (ranging from 9.9 to 12. 8 ms/ng ml(-1). CONCLUSIONS: The pharmacokinetics
      and pharmacodynamics of dofetilide are predictable and based on a linear
      relationship for both twice daily and three times daily dosing regimens. The QT
      responsiveness to dofetilide is greater on day 1 than on day 5.

PMID- 10971308
TI  - Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse
      effects of morphine.
AB  - AIMS: To investigate the effect of acute P-glycoprotein inhibition by the
      multidrug-resistance (MDR) modulator valspodar (SDZ PSC 833; PSC) on the
      pharmacokinetics, and potentially adverse pharmacodynamic effects of morphine,
      and its principal pharmacologically active metabolites, morphine-3-glucuronide
      (M3G) and morphine-6-glucuronide (M6G). METHODS: In a double-blind, three-way
      crossover study, the pharmacokinetic and potentially adverse pharmacodynamic
      effects (reaction time, transcutaneous PCO2, blood pressure) of morphine were
      compared with and without acute inhibition of P-glycoprotein by PSC. The effects
      of PSC alone were also evaluated. The study was performed in 18 healthy male
      volunteers and pharmacodynamic effects analysed by measuring the area under the
      effect (AUE) curve. 150 mg PSC (or its placebo) was given as an i.v. infusion
      over 2 h. With the expected inhibition of Pgp 1 h after starting PSC infusion,
      7.5 morphine HCl (or its placebo) was infused over 2 h. RESULTS: The infusion of
      PSC resulted in blood concentrations expected to inhibit Pgp mediated transport.
      While the pharmacokinetics of plasma morphine and M6G. were unaffected there was
      a small but statistically significant increase in the AUC and Cmax of M3G (11.8
      and 8.3%, respectively). The t(1/2) and tmax were unaffected. The pharmacokinetic
      parameters of PSC were not affected by coadministration with morphine. PSC did
      not significantly affect the adverse events of morphine, as assessed by
      spontaneous reporting. Compared with PSC alone, morphine elicited an increase in
      reaction time (Emax 48 ms, compared with the predose absolute reaction time of
      644 ms), which was not detected by the alertness-drowsiness score, indicating
      only slight sedation. There was a significant decrease in systolic blood pressure
      (Emin -9 mm Hg), and a trend for a fall in diastolic blood pressure (Emin -14.5
      mm Hg) and respiratory rate (Emin -1.8 breath x min(-1)). For all these
      parameters, the effects of PSC/morphine were similar to that of PSC alone,
      suggesting some attenuation of morphine's effect. In contrast, morphine caused a
      significant increase in PCO2 (Emax 0.69 kPa) compared to PSC alone, indicating
      slight respiratory depression. This increase was similar to that of the
      PSC/morphine combination. CONCLUSIONS: Acute inhibition of P-glycoprotein by PSC
      in this setting does not affect the pharmacokinetic or safety-related
      pharmacodynamic profile of morphine in a clinically significant manner.

PMID- 10971311
TI  - Citalopram and demethylcitalopram in human milk; distribution, excretion and
      effects in breast fed infants.
AB  - AIMS: To characterize milk/plasma (M/P) ratio and infant dose, for citalopram and
      demethylcitalopram, in breast-feeding women taking citalopram for the treatment
      of depression, and to determine the plasma concentration and effects of these
      drugs in their infants. METHODS: Seven women (mean age 30.6 years) taking
      citalopram (median dose 0.36 mg kg(-1) day(-1)) and their infants (mean age 4.1
      months) were studied. Citalopram and demethylcitalopram in plasma and milk were
      measured by high-performance liquid chromatography over a 24 h dose interval.
      Infant exposure was estimated (two separate methods) as the product of milk
      production rate and drug concentration in milk, normalized to body weight and
      expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean
      M/PAUC values of 1.8 (range 1.2-3) and 1.8 (range 1.0-2.5) were calculated for
      citalopram and demethylcitalopram, respectively. The mean maximum concentrations
      of citalopram and demethylcitalopram in milk were 154 (95% CI, 102-207) microg l(
      1) and 50 (23-77) microg l(-1). Depending on the method of calculation, mean
      infant exposure was 3.2 or 3.7% for citalopram and 1.2 or 1.4% for
      demethylcitalopram. Citalopram (2.0, 2.3 and 2.3 microg l(-1)) was detected in
      three of the seven infants. Demethylcitalopram (2.2 and 2.2 microg l(-1) was
      detected in plasma from two of the same infants. No adverse effects were seen in
      the infants, all were within appropriate percentile limits for weight and all had
      normal Denver developmental quotients. CONCLUSIONS: The mean combined dose of
      citalopram and demethylcitalopram (4.4-5.1% as citalopram equivalents)
      transmitted to infants via breast milk is below the 10% notional level of
      concern. Plasma concentrations of these drugs in the infants were very low or
      absent and there were no adverse effects. These data support the safety of the
      use of citalopram in breast feeding women. Nevertheless, each decision to breast
      feed should always be made as an individual risk:benefit analysis.

PMID- 10971310
TI  - Effects of policosanol treatment on the susceptibility of low density lipoprotein
      (LDL) isolated from healthy volunteers to oxidative modification in vitro.
AB  - AIMS: The aim of this study was to investigate the effect of policosanol on the
      susceptibility of LDL-C to in vitro lipid peroxidation in human healthy
      volunteers. METHODS: The effect of policosanol (5 and 10 mg day(-1) on LDL-C
      oxidation was studied in a double-blind, randomized, placebo-controlled trial
      conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks
      were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility
      of LDL-C to lipid peroxidation in a cell-free system by the addition of copper
      ions as well as in a more physiological system, macrophage-mediated oxidation.
      RESULTS: At baseline all groups were well matched regarding all variables. After
      8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in
      a dose-dependent manner increased the lag phase of conjugated diene generation
      (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and
      from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the
      placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg
      day(-1)), but not placebo, significantly decreased the rate of conjugated diene
      generation. Comparison with placebo after therapy also showed significant
      differences. Macrophage mediated-oxidation was also inhibited by policosanol as
      evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol
      (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from
      8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5
      and 10 mg day(-1) showed significant differences. Policosanol significantly
      lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and
      LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1))
      increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of
      adverse experiences. No clinical or blood biochemical drug-related disturbances
      were found. CONCLUSIONS: The present study demonstrated that policosanol
      administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg
      day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.

PMID- 10971312
TI  - Evaluation of dihydropyrimidine dehydrogenase activity in South-west Asian,
      Kenyan and Ghanaian populations.
AB  - AIMS: Dihydropyrimidine dehydrogenase (DPD) reduces endogenous pyrimidines and
      therapeutic analogues such as the anticancer agent 5-fluorouracil (5FU). Among
      Caucasian populations DPD activity is highly variable and subject to polymorphic
      regulation. To evaluate interethnic influence, DPD activity was assessed in South
      west Asian, Kenyan and Ghanaian populations. METHODS: DPD activity was determined
      in peripheral mononuclear cells using[14C]-5-fluorouracil and h.p.l.c. analysis.
      RESULTS: A high degree of variation in DPD activity was observed within each
      population (range CV = 34-48%). Median DPD activity also varied between these
      populations. South-west Asian and Kenyan subjects exhibited almost identical
      median values (192 and 193.5 pmol min(-1) mg(-1), respectively), which were
      similar to Caucasians (median 215 pmol min(-1) mg(-1). A significantly lower
      median DPD activity (119 pmol min(-1) mg(-1)) was observed in the Ghanaian
      population. CONCLUSIONS: The similarity in DPD activity between Caucasian, Kenyan
      and South-west Asian populations suggests that the incidence of 5FU-related
      toxicity may be comparable in these groups. The pharmacokinetic implications of
      lower activity amongst Ghanaians needs to be evaluated.

PMID- 10971313
TI  - Intravenous diltiazem and CYP3A-mediated metabolism.
AB  - AIMS: To study whether intravenous diltiazem, a calcium channel blocker commonly
      prescribed for hypertension and stable angina, is an inhibitor of the CYP3A
      enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a
      substrate. METHODS: Ten healthy volunteers were studied in a randomized two-way
      crossover design. The two arms were 1) administration of a 20 mg dosage of
      lovastatin orally and 2) administration of a 20 mg dosage of lovastatin orally 1
      h after an intravenous loading dosage and constant infusion of diltiazem. Blood
      samples were collected up to 25 h in order to quantify lovastatin and diltiazem
      concentrations in the separated serum. Lovastatin and diltiazem concentrations
      were quantified by GC-MS and h.p.l.c., respectively. RESULTS: Intravenous
      diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of
      lovastatin. CONCLUSIONS: These data suggest that the interaction of lovastatin
      with diltiazem does not occur systemically and is primarily a first-pass effect.
      Thus, drug interactions with diltiazem may become evident when a patient is moved
      from intravenous to oral dosing.

PMID- 10971314
TI  - Reducing electrostatic charge on spacer devices and bronchodilator response.
AB  - AIMS: Plastic spacers are widely used with pressurized metered dose inhalers
      (pMDI). Reducing electrostatic charge by washing spacers with detergent has been
      shown to greatly improve in vitro and in vivo drug delivery. We assessed whether
      this finding is associated with an improved bronchodilator response in adult
      asthmatics. METHODS: Twenty subjects (age 18-65 years) with a known
      bronchodilator response inhaled in random order salbutamol from a pMDI (Ventolin)
      through an untreated new spacer (Volumatic) and through a detergent washed
      spacer. Patients received the following doses of salbutamol via pMDI at 20 min
      intervals: 100 microg, 100 microg, 200 microg, 400 microg, 800 microg.
      Spirometry, heart rate and blood pressure were checked prior to each dose and 20
      min after the last dose. RESULTS: There were no differences between baseline
      forced expiratory volume in 1 s (FEV1) using either spacer (2.61+/-0.56 and
      2.52+/-0.45 l, untreated and treated with detergent, respectively; mean +/-
      s.d.). The provocation dose required to cause a clinically significant
      improvement of 10% in FEV1 (PD10) was significantly lower when the detergent
      treated spacer was used (1505 +/-1335 and 430+/-732 microg, untreated and
      treated, respectively, P<0.002). CONCLUSIONS: We have demonstrated an improvement
      in bronchodilator response, in adult asthmatics, after reducing the electrostatic
      charge in a spacer device by washing it with ordinary household detergent. This
      finding stresses the importance of an optimal choice of delivery device for
      asthma medication.

PMID- 10971315
TI  - Relative bioavailability of salbutamol to the lung following inhalation when
      administration is prolonged.
AB  - AIMS: Urinary salbutamol post-inhalation has been shown to be an index of lung
      deposition. The possibility of using the urinary method for prolonged periods of
      inhalation (such as nebulized therapy) has been evaluated. METHODS: On separate
      study days volunteers received salbutamol 5 x 100 microg via either oral
      administration (ORAL), oral with 5 g oral charcoal (ORAL + C), inhaled from a
      metered dose inhaler (MDI) or MDI plus 5 g oral charcoal (MDI + C). Each dose was
      separated by 2 min, i.e. administration time of 8 min. Urine samples were
      provided at 0, 30, 40, 60 and 120 min postdose. Also seven subjects inhaled 5x100
      microg doses from the MDI on five separate occasions and provided urine 0-30 min
      post dose. RESULTS: No salbutamol was detected in urine samples following ORAL +
      C. The mean (s.d.) amounts of salbutamol excreted in the urine in the first 30
      min post ORAL, MDI and MDI + C were 0.42 (0.55), 11.01 (3.77) and 11.60 (3.68)
      microg, respectively. The ratio of urinary salbutamol following MDI and MDI + C
      to ORAL in the 0-30 min collection period was 26.2 and 27.8, and between 30 and
      40 min postdose was 5.1 and 4.7, respectively. There was no difference between
      urinary salbutamol over the first 30 min following MDI and MDI + C with a mean
      ratio (90% confidence interval) of 95.6 (84.0, 107.2). The mean (s.d.)
      coefficient of variation for the 30 min urinary salbutamol elimination following
      inhalation of 5 x 100 microg doses from the MDI by seven subjects (on 5 separate
      study days) was 9.4 (2.3)%. CONCLUSIONS: The 30 min urinary salbutamol method can
      be used for an inhalation period of up to 8 min to identify the relative
      bioavailability to the lung. Samples taken after this time period are affected by
      excretion of the oral absorbed fraction. Most nebulisers deliver their dose
      within this administration time.

PMID- 10971316
TI  - The confusing state of the histiocytoses.

PMID- 10971317
TI  - Photoadaptation to ultraviolet (UV) radiation in vivo: photoproducts in epidermal
      cells following UVB therapy for psoriasis.
AB  - BACKGROUND: Ultraviolet (UV) radiation is mutagenic and induces specific DNA
      lesions in human skin that are often found at dipyrimidine sites. These
      photoproducts are likely to be biologically relevant regarding skin
      carcinogenesis, as p53 mutations in skin tumours are most often found at these UV
      radiation-specific sites within DNA. Psoriasis patients receiving long-term
      phototherapy are at an increased risk of non-melanoma skin cancers. OBJECTIVES:
      The aim of this study was to quantify DNA photoproducts in human epidermis in
      vivo following consecutive doses of UVB and to investigate variations in DNA
      damage according to skin type, UVB dose and age. METHODS: Eleven psoriasis
      patients receiving UVB phototherapy three times a week were recruited and
      underwent skin biopsies on a non-sun-exposed site before starting phototherapy
      and after three, nine and 18 UVB exposures. A biopsy was also taken at least 4
      weeks after stopping phototherapy. DNA was extracted from separated epidermis and
      three types of photoproducts were quantified using a novel 32P high-performance
      liquid chromatographic technique. RESULTS: The mean level of cyclobutane
      dipyrimidine dimers (CPDs) after three doses of UVB (dose range 0.03-0.15 J cm-2)
      was 3.2 (range 0.8-8.9) photoproducts per 106 normal nucleotides for TT=T dimers
      and 4.5 (range 0-14) per 106 normal nucleotides for TT=C dimers. The mean levels
      of TT-C 6-4 photoproducts after three doses of UVB were very low (0.2, range 0
      1.8). Overall, the levels of TT=T and TT=C reached a plateau at three exposures
      and were found to decrease for subsequent exposures despite increasing UVB doses.
      Skin type was negatively associated with mean levels of CPDs. However,
      significant differences in levels of photoproducts were seen between individuals,
      even after adjusting for skin type. No association was found between challenge
      dose of UVB and photoproduct yield in this study. CONCLUSIONS: This study showed
      a great individual variation in the accumulation of DNA photoproducts following
      exposure to repetitive doses of UVB. Photoadaptive responses of human skin
      involving DNA repair, tanning and epidermal thickening are likely to explain the
      overall lack of increase in DNA lesions throughout phototherapy. This in vivo
      study confirms that psoriasis patients produce a significant amount of DNA
      photolesions at suberythemal doses of UVB. Further work is needed to investigate
      which host factors are most likely to predict susceptibility to UV radiation
      induced DNA damage.

PMID- 10971318
TI  - Antibodies against human herpesvirus 8 in subjects with non-venereal
      dermatological conditions.
AB  - BACKGROUND: Human herpesvirus 8 (HHV8) is considered as the infectious cofactor
      involved in the pathogenesis of Kaposi's sarcoma (KS). Its seroprevalence and
      modes of transmission in the general population are still undetermined.
      OBJECTIVES: We aimed to estimate the prevalence of HHV8 infection in a population
      at low risk for sexually transmitted diseases. METHODS: We conducted a
      seroepidemiological survey on randomly selected individuals attending the
      dermatology department of a teaching hospital in Rome. Of 257 patients, 248 had
      their blood analysed for anti-HHV8 antibodies and 201 completed a standardized
      interview. Serological analysis was performed by an immunofluorescence assay able
      to detect antilytic antibodies. RESULTS: We found an overall seroprevalence of
      15.7% (95% confidence interval, CI 11.4-20.9%), similar in men and women (15.1%
      vs. 16.3%) and higher at older ages. Seropositivity was not related to sexual
      habits, while it was significantly associated with a history of hepatitis
      (seroprevalence 34.6%, adjusted odds ratio, OR 4.08, 95% CI 1.52-11.00) and with
      a diagnosis of non-melanoma skin cancer (42.9%, OR 4.20, 95% CI 1.26-14.02) or
      atypical naevi (35.3%, OR 6.21, 95% CI 1.85-20.86). CONCLUSIONS: Our data suggest
      that a non-sexual mode of transmission of HHV8 infection is plausible in an
      Italian population at low risk for sexually transmitted diseases and that other
      factors, besides differences in prevalence of HHV8 infection, may be involved in
      the epidemiology of classical KS. The unexpectedly high seropositivity rates in
      subjects with non-melanoma skin cancer and atypical naevi should be viewed with
      caution and require confirmation.

PMID- 10971319
TI  - Ceramide 2 (N-acetyl sphingosine) is associated with reduction in Bcl-2 protein
      levels by Western blotting and with apoptosis in cultured human keratinocytes.
AB  - BACKGROUND: Ceramides produced by sphingomyelin hydrolysis activate a cycle that
      is followed by three different major cellular responses: downregulation of cell
      proliferation, induction of cell differentiation and apoptosis. In the skin, the
      generation of intracellular ceramide may also provide a link between an
      extracellular signal and the induction of the apoptosis programme for the
      elimination of damaged cells. OBJECTIVES: We investigated the effect of ceramides
      capable of entering cells on cultured keratinocytes. METHODS: Human keratinocytes
      from neonatal skin were cultured in serum-free medium with or without increasing
      concentrations of ceramide 2 (CER-2; N-acetyl sphingosine) (5, 10, 20 and 40
      micromol L-1). Proliferative effects were studied either by cell counts or by 3H
      thymidine incorporation and flow cytometric analysis. Apoptosis was studied by
      TUNEL staining and Western blot analysis of Bcl-2 protein. RESULTS: Cell counts
      and DNA synthesis were reduced in a dose-dependent manner following CER-2
      treatment. TUNEL staining showed CER-2-induced apoptosis at 48, 72 and 96 h.
      Western blot analysis showed that CER-2 induces downregulation of Bcl-2 at 24-96
      h. CONCLUSIONS: These results demonstrate that CER-2 inhibits cell proliferation
      and induces apoptosis, possibly via a Bcl-2-dependent mechanism.

PMID- 10971320
TI  - A multicentre, single-blind, randomized comparison of a fixed clindamycin
      phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin
      lotion formulation (Dalacin T) applied twice daily in the topical treatment of
      acne vulgaris.
AB  - BACKGROUND: A successful phase III pilot study compared the efficacy and safety
      of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel)
      applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T
      lotion) applied twice daily in the treatment of moderate to severe acne vulgaris.
      OBJECTIVES: We aimed to follow up this study. METHODS: The two treatment regimens
      were compared in a multicentre, single-blind, randomized 12-week investigation of
      patients with moderate to severe acne vulgaris. RESULTS: At week 12, the mean
      percentage reduction in non-inflamed lesions (open and closed comedones) was
      greater in the CTG group compared with the CLN group (P = 0.05). Absolute
      reductions in open and closed comedones were also greater in the CTG group,
      consistent with the comedolytic activity of tretinoin. There was a significantly
      greater absolute reduction in inflamed lesions (pustules, papules and nodules)
      from baseline to both end-point (last observed efficacy outcome; P = 0.043) and
      week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of
      the calculated overall acne severity score, considering all five lesion subtypes,
      demonstrated a significantly greater mean percentage reduction in the CTG group
      compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P <
      0.01). The more subjective assessment of overall acne severity according to the
      Cook scale also demonstrated a significantly greater mean reduction in the CTG
      group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more
      rapid effect on the onset of improvement compared with CLN; a 50% reduction in
      total lesion counts by day 60 was found in 77% of patients on CTG compared with
      56% receiving CLN (P = 0.003). This was largely due to the reduction in open
      comedone counts (P = 0. 0006). For all other variables, CTG was at least as
      effective as CLN. Both treatments were well tolerated. CONCLUSIONS: A single
      daily topical application of Velac gel was superior to Dalacin T lotion applied
      twice daily in reducing overall acne scores, and was faster acting. The simpler
      dosing regimen of Velac gel and its rapid effect are likely to have a positive
      effect on both patient compliance and cost.

PMID- 10971321
TI  - Stimulatory effects of dibutyryl cyclic adenosine monophosphate on cytokine
      production by keratinocytes and fibroblasts.
AB  - BACKGROUND: Clinical studies have shown that ointment containing dibutyryl cyclic
      adenosine monophosphate (DBcAMP) promotes wound healing. OBJECTIVES: We aimed to
      elucidate the mechanisms of the beneficial effect of DBcAMP in wound healing.
      METHODS: An investigation was made of the effects of DBcAMP on in vitro cytokine
      release from cultured keratinocytes and fibroblasts derived from normal human
      skin. RESULTS: DBcAMP stimulated keratinocyte proliferation through increased
      interleukin (IL)-6 production by fibroblasts, and transiently enhanced production
      of transforming growth factor (TGF)-beta1 by fibroblasts at an early stage of
      incubation. DBcAMP also stimulated fibroblast proliferation, resulting in further
      increases in IL-6 and TGF-beta1. CONCLUSIONS: We conclude that this series of
      stimulative actions on cytokine secretion, together with the facilitation of cell
      proliferation, contribute to the effects of DBcAMP on the healing of skin ulcers.

PMID- 10971322
TI  - Incidence of skin cancer in 5356 patients following organ transplantation.
AB  - BACKGROUND: Skin cancer following solid organ transplantation is an important
      cause of morbidity in long-term survivors. This risk is well known but
      imprecisely quantified. OBJECTIVES: We aimed to determine: (i) the skin cancer
      risks in transplant patients more precisely; (ii) whether the risk of malignant
      melanoma is altered; and (iii) whether the risk of epithelial cancers occurring
      at non-exposed sites is comparable with that seen in sun-exposed sites. METHODS:
      We linked a population-based cohort of 5356 patients who had received organ
      transplants in Sweden between 1970 and 1994 with the compulsory Swedish Cancer
      Registry, to identify all cancer cases except basal cell carcinomas, which are
      not registered. RESULTS: After a mean follow-up of 5.6 years post
      transplantation, 172 of 5356 patients developed 325 non-melanoma skin cancers
      (excluding basal cell carcinomas) and six malignant melanomas. The relative risk
      of non-melanoma skin cancer was 108.6 [95% confidence interval (CI) 94.6-123.1]
      for men and 92.8 (95% CI 73.2-116.0) for women. The highest risks were noted for
      upper limbs, and the risk increased with time. No significant increase in
      malignant melanomas was noted: the relative risk was 1.6 (95% CI 0.5-3.7) for men
      and 0.5 (95% CI 0. 0-2.6) for women. Except for the lip, which is also sun
      exposed, other epithelial sites did not show comparable increases in cancer risk.
      CONCLUSIONS: We conclude that organ transplant recipients are at a highly
      increased risk for non-melanoma skin cancer and must be closely followed
      throughout their lives. Cancer risk associated with transplantation is higher for
      sun-exposed than for non-sun-exposed epithelial tissues, even among populations
      living in regions with low solar insolation.

PMID- 10971324
TI  - Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum
      lipids to improve the epidermal permeability barrier.
AB  - BACKGROUND: Stratum corneum lipids, particularly ceramides, are important
      components of the epidermal permeability barrier that are decreased in atopic
      dermatitis and aged skin. OBJECTIVES: We investigated the effects of
      nicotinamide, one of the B vitamins, on biosynthesis of sphingolipids, including
      ceramides and other stratum corneum lipids, in cultured normal human
      keratinocytes, and on the epidermal permeability barrier in vivo. METHODS: The
      rate of sphingolipid biosynthesis was measured by the incorporation of [14C]
      serine into sphingolipids. RESULTS: When the cells were incubated with 1-30
      micromol L-1 nicotinamide for 6 days, the rate of ceramide biosynthesis was
      increased dose-dependently by 4.1-5. 5-fold on the sixth day compared with
      control. Nicotinamide also increased the synthesis of glucosylceramide (7.4-fold)
      and sphingomyelin (3.1-fold) in the same concentration range effective for
      ceramide synthesis. Furthermore, the activity of serine palmitoyltransferase
      (SPT), the rate-limiting enzyme in sphingolipid synthesis, was increased in
      nicotinamide-treated cells. Nicotinamide increased the levels of human LCB1 and
      LCB2 mRNA, both of which encode subunits of SPT. This suggested that the increase
      in SPT activity was due to an increase in SPT mRNA. Nicotinamide increased not
      only ceramide synthesis but also free fatty acid (2.3-fold) and cholesterol
      synthesis (1.5-fold). Topical application of nicotinamide increased ceramide and
      free fatty acid levels in the stratum corneum, and decreased transepidermal water
      loss in dry skin. CONCLUSIONS: Nicotinamide improved the permeability barrier by
      stimulating de novo synthesis of ceramides, with upregulation of SPT and other
      intercellular lipids.

PMID- 10971323
TI  - The use of ivermectin in controlling an outbreak of scabies in a prison.
AB  - BACKGROUND: Ivermectin is a potentially useful treatment for scabies. OBJECTIVES:
      We aimed to evaluate the efficacy of ivermectin in the treatment of scabies in an
      institutional environment. METHODS: A single dose of ivermectin 150 microg kg-1
      was given under supervision to 1153 prisoners in a prison in northern Tanzania
      where there was an outbreak of scabies. RESULTS: Thirty per cent of the prisoners
      were cured after 1 week, 88% after 4 weeks and 95.5% after 8 weeks. Of 16
      prisoners with crusted scabies, seven (44%) still had scabies after 8 weeks.
      Those who were not cured were then treated with 1% lindane lotion topically, as
      were the prison staff who had scabies. This regimen eradicated scabies from the
      prison for the next 2 years. CONCLUSIONS: Ivermectin is an effective and safe
      treatment for scabies, particularly in a closed community, such as a prison,
      where it is easy to administer and avoids problems with compliance. It was of
      limited efficiency in crusted scabies as a single dose and we recommend that for
      such patients oral ivermectin is used in combination with a topical scabicide.

PMID- 10971325
TI  - Change in ultraviolet (UV) transmission following the application of vaseline to
      non-irradiated and UVB-exposed split skin.
AB  - BACKGROUND: Topical preparations such as emollients used in combination with
      phototherapy can interfere with such treatment. OBJECTIVES: This study was
      performed to investigate the impact of vaseline on the ultraviolet (UV)
      transmission of non-irradiated split skin and on split skin previously exposed to
      UVB radiation. METHODS: Split-skin specimens were obtained from 20 patients. In
      each case, one sample was taken from an area of non-irradiated skin, while the
      second was taken from an area that had been previously exposed to UVB. The
      transmission was spectrophotometrically measured with split skin placed in
      specially designed quartz glass cuvettes before and after the application of two
      different amounts of vaseline (2.5 and 17.5 mg cm-2). RESULTS: Application of
      vaseline to skin previously exposed to UVB caused significant (P < 0.0001)
      changes in UV transmission in certain wavelength ranges. In the UVA range, a
      greater increase in transmission was achieved with 2.5 mg cm-2 vaseline, whereas
      in the UVB range, a greater increase was achieved with 17.5 mg cm-2 vaseline. The
      thicker the layer of vaseline applied, the lower was the difference in
      transmission between non-irradiated split skin and UVB-exposed split skin.
      CONCLUSIONS: Application of the correct amount of vaseline can enhance
      transmission in either the UVA or UVB range, and would enable dose reduction
      during a course of phototherapy.

PMID- 10971326
TI  - Transforming growth factor-beta1 and ultraviolet A1 radiation increase production
      of vascular endothelial growth factor but not endothelin-1 in human dermal
      fibroblasts.
AB  - BACKGROUND: Normal and dysregulated wound healing involves fibroblast activation
      and angiogenesis, in which polypeptide factors such as transforming growth factor
      (TGF)-beta, vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1)
      play an important part. Ultraviolet (UV) A1 (365 nm) has recently received
      attention as a possible treatment for some dermal fibrotic disorders. OBJECTIVES:
      The aim of this study was to evaluate the effects of TGF-beta1 and UVA1
      radiation, as well as that of cobalt chloride, reported to mimic hypoxia both in
      vivo and in vitro, on the expression of VEGF and ET-1 by cultured human dermal
      fibroblasts. METHODS: Levels of VEGF and ET-1 were measured by enzyme-linked
      immunosorbent assay and expression of neutral endopeptidase (NEP, CD10), known to
      degrade ET-1, was quantified by flow cytometric analysis after cell
      trypsinization. RESULTS: Our results showed that the cells released minor amounts
      of VEGF and ET-1. Both TGF-beta1 and UVA1 strongly increased VEGF secretion in a
      dose- and time-dependent manner, without significantly affecting ET-1 release.
      Irradiation of TGF-beta1-stimulated fibroblasts resulted in a synergistic effect
      on increasing levels of VEGF but not ET-1 after 48 h. Cobalt chloride stimulated
      the secretion of VEGF by fibroblasts; the effects of TGF-beta1 and cobalt were
      additive. However, no significant effect of cobalt chloride on ET-1 secretion was
      observed, suggesting that ET-1 production in fibroblasts is not oxygen-sensitive.
      The expression of NEP was not modified by TGF-beta1 or UVA1 radiation. Addition
      of a neutralizing anti-CD10 antibody to fibroblast cultures downregulated CD10
      expression at the cell surface without changing ET-1 levels in cell supernatants
      after 24 or 48 h. This suggests that membrane-bound NEP has minimal or no
      activity against secreted ET-1. CONCLUSIONS: Taken together, these results
      underline the major role played by TGF-beta1 in increasing VEGF secretion by
      fibroblasts. This, as well as the documented effect of UVA1 on increasing VEGF
      production, may have implications for wound healing in vivo.

PMID- 10971327
TI  - Skin tolerance and effectiveness of two hand decontamination procedures in
      everyday hospital use.
AB  - BACKGROUND: Hand decontamination is crucial to control nosocomial infections. The
      utility of hand decontamination is related not only to its antimicrobial
      effectiveness, but also to its acceptability by hospital staff. OBJECTIVES: We
      aimed to assess skin tolerance and antimicrobial effects of two widely accepted
      hand hygiene measures under in-use conditions. METHODS: Fifty-two nurses were
      randomly assigned for an 8-day period to either an alcohol-based disinfectant or
      a hand wash with a non-antiseptic soap. At baseline and at the end of the test
      period, microbiological hand samples were obtained both before and after a hand
      hygiene procedure, and skin tolerance was assessed using clinical scores and
      measurement of transepidermal water loss. RESULTS: Self-assessment of skin
      condition and grade of skin damage worsened significantly more in the group using
      soap than in the group using alcoholic disinfectant (P = 0.004 and P = 0.01,
      respectively). The alcohol-based rinse was significantly more effective than
      liquid soap in removing transient contaminant micro-organisms (P = 0.016). Twenty
      of 50 hand washes with non-antiseptic soap apparently resulted in bacterial
      contamination of the hands. At the end of the study, the total bacterial count
      increased with the increasing number of hand washes in the soap group (P =
      0.003), and with the degree of skin damage (P = 0.005) in the antiseptic group.
      CONCLUSIONS: In everyday hospital practice, alcohol-based disinfectant is more
      effective and better tolerated than non-antiseptic soap; soap is at risk of
      spreading contamination; and skin comfort strongly influences the number and the
      quality of hand hygiene procedures.

PMID- 10971328
TI  - Experimental irritant contact dermatitis due to cumulative epicutaneous exposure
      to sodium lauryl sulphate and toluene: single and concurrent application.
AB  - In clinical practice, cutaneous exposure to a variety of irritants such as
      surfactants and solvents is frequent. Although the induction of irritant
      dermatitis by single irritants has been extensively studied in recent years, our
      knowledge of the effects of simultaneous application of different irritants is
      limited. Using non-invasive techniques for measurements of transepidermal water
      loss (TEWL) and skin colour reflectance, we quantified the irritant effects of
      single and concurrent application of 0.5% sodium lauryl sulphate (SLS) and
      undiluted toluene (TOL) in vivo. The irritants were applied twice daily for 30
      min to the volar forearms of 20 volunteers. Repeated application of SLS and TOL
      induced an irritant reaction, as indicated by an increase in TEWL and skin
      redness. In contrast to SLS alone, the application of TOL alone induced only a
      moderate increase in TEWL, confirming previous results. Concurrent application of
      SLS/TOL and TOL/SLS induced significantly stronger reactions than those caused by
      twice daily application of each irritant on its own. Our results demonstrate that
      a mixed application of an anionic detergent and an organic solvent has an
      additive effect on skin irritation. It is suggested that pretreatment with SLS
      causes an increased susceptibility to TOL irritation and vice versa. Thus, the
      necessity for special precautions against skin absorption of TOL when handling
      detergents such as SLS is emphasized.

PMID- 10971329
TI  - Phenotypic characteristics of Kaposi's sarcoma tumour cells derived from patch-,
      plaque- and nodular-stage lesions: analysis of cell cultures isolated from AIDS
      and non-AIDS patients and review of the literature.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is commonly thought to be derived from
      endothelial cells because of the predominant expression of endothelial markers in
      KS lesions. However, the heterogeneity of the spindle-cell compartment makes the
      precise lineage relationship of KS tumour cells unclear. Cultured KS-derived
      spindle cells constitutively overexpress antiapoptotic proteins and exhibit
      invasive properties, which suggests that they may adequately represent the tumour
      cells of KS. OBJECTIVES: We aimed to investigate the expression of a wide variety
      of immunohistochemical markers by spindle cells derived from patch-, plaque- and
      nodular-stage lesions from patients with iatrogenic, sporadic and acquired immune
      deficiency syndrome-related KS, and to review the data reported by other
      laboratories. METHODS: Cells from six KS cell cultures derived from four subjects
      were examined by immunostaining. RESULTS: Comparison of these data indicates that
      KS-derived spindle cells generally express myofibroblast antigens but lack
      endothelial and/or leucocyte markers. CONCLUSIONS: As the myofibroblast phenotype
      is not the predominant feature of KS tissues, our findings further substantiate
      the view that the in vivo dominant endothelial population represents a reactive
      hyperplasia rather than the true KS tumour process.

PMID- 10971330
TI  - The influence of the vehicle on the synthesis of porphyrins after topical
      application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic
      sensitization.
AB  - BACKGROUND: The optimal vehicle to ensure adequate penetration of 5
      aminolaevulinic acid (ALA) for its use in photodynamic therapy (PDT) of skin
      lesions has not been determined. OBJECTIVES: We aimed to study the effects of ALA
      in various vehicle formulations [saline lotion with and without
      dimethylsulphoxide (DMSO), cream, liposomes and vaseline] after topical
      application in a murine subcutaneous adenocarcinoma model. METHODS: The effect of
      DMSO on porphyrin synthesis and ALA penetration through the skin was studied by
      measuring the uptake of 14C label from ALA, ALA and porphobilinogen accumulation,
      and some haem enzyme activities. The tissue distribution and kinetics of
      porphyrin synthesis after topical application of ALA entrapped in large
      multilamellar liposomes was also determined. RESULTS: ALA in saline lotion, alone
      or with 10% DMSO, proved to be the most efficient vehicle for tumour porphyrin
      accumulation (mean +/- SD 1.75 +/- 0.25 and 2.09 +/- 0.39 microg g-1,
      respectively), whereas cream and liposomes induced lower levels and identical
      porphyrin accumulation (0.60 microg g-1). Using ALA + DMSO saline lotion, a
      higher porphyrin accumulation was found in skin overlying the tumour tissue and
      in the first 2 mm of tumour, probably due to increased ALA penetration, or
      greater interconversion to porphyrins, or greater retention of ALA and/or
      porphyrins. CONCLUSIONS: These findings reinforce the importance of the vehicle
      in topical ALA-based PDT, and explain the mechanism of action of DMSO in
      enhancing protoporphyrin IX biosynthesis in superficial lesions.

PMID- 10971331
TI  - Expression and modulation of apoptosis regulatory molecules in human melanocytes:
      significance in vitiligo.
AB  - Although the aetiology of the hypopigmentary disorder vitiligo is ill understood,
      it is clear that pigment producing cells are absent from vitiliginous lesional
      skin. The present study was designed to investigate the possible role of
      melanocyte-expressed apoptosis regulatory molecules in melanocyte disappearance.
      Flow cytometric evaluation of p53, p21, Bcl-2 and Bax revealed no differences in
      in vitro expression levels between normal control and non-lesional melanocytes.
      Moreover, no in situ immunohistological differences were observed in melanocytes
      present in control, non-lesional and perilesional skin. However, an enhanced
      number of p53+ nuclei, in the absence of detectable p21 expression, was detected
      in involved areas. The observed p53 expression pattern did not involve
      melanocytes and could be the result of ultraviolet (UV) A irradiation. Further,
      we showed that UVB is capable of modulating melanocyte-expressed apoptosis
      regulatory molecules. Consequently, a lethal dose of UVB was given to two groups
      of cultured normal control and non-lesional melanocytes. No significant
      differences were found when comparing the percentages and kinetics of UVB-induced
      apoptosis in these groups. In conclusion, our results indicate that the relative
      apoptosis susceptibility of melanocytes in vitiligo is comparable with that of
      normal control cells. It is therefore unlikely that vitiligo is causally related
      to dysregulation of apoptosis regulatory molecules.

PMID- 10971332
TI  - (Un)usual effects of patch testing?
AB  - BACKGROUND: Little information is available concerning subjective complaints
      associated with patch testing. OBJECTIVES: To gather information about the
      frequency and the nature of such complaints, and to evaluate, if possible,
      whether the complaints were really caused by patch testing. PATIENTS/METHODS:
      Four hundred and thirty-three patients took part in a questionnaire study between
      December 1996 and October 1997. Complaints of itch and other subjective
      complaints, such as tiredness and feeling unwell, were recorded. RESULTS: From
      the total group of 433 patients, 379 patients (87%) recorded one or more
      complaints on day 0. By day 2 this number was 383 patients (88%), with a
      significant reduction to 326 patients (75%) by days 3-4. Most complaints
      concerned itch on the back, and to a lesser extent tiredness. Fifty-four patients
      (54 of 433; 12%) did not report itch or other subjective complaints on day 0; of
      this group, 36 patients (66%) developed complaints by day 2. By days 3-4, 24
      patients (44%) reported complaints: 20 patients from the day 2 group (37%) and
      four patients (7%) from days 3-4. Again the largest increase in complaints was
      found for itch on the back, but other complaints were also found to have
      increased, mainly tiredness, feeling unwell, headache, shakiness and light
      headedness. CONCLUSIONS: We conclude that patch testing can, in addition to local
      skin reaction and itch, also cause other subjective complaints in a number of
      patients.

PMID- 10971333
TI  - A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic
      syndrome.
AB  - We describe a 70-year-old man with cutaneous granulocytic sarcoma who presented
      with numerous cutaneous nodules but without any leukaemic involvement of the
      peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a,
      CD11c, CD33 and HLA-DR, and weakly positive for CD4 and CD14, suggesting
      granulocytic differentiation. The bone marrow at admission showed dysplasia of
      the erythrocytic and granulocytic lineage and complex chromosomal abnormalities
      in association with an increase in monocytes. The patient was diagnosed as having
      granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic
      syndrome. In this case, tumour cells also expressed the neural cell adhesion
      molecule (CD56), which has been suggested as a possible risk factor for
      developing granulocytic sarcoma in acute myelogenous leukaemia.

PMID- 10971334
TI  - Eccrine syringofibroadenoma in a patient with a burn scar ulcer.
AB  - A 72-year-old woman with a burn scar on the calves of both legs developed an
      ulcer on her right heel, surrounded by multiple verrucous nodules and plaques.
      She had experienced similar verrucous lesions on both legs in the burn scar
      areas. Although the clinical diagnosis was Marjolin's ulcer, histologically the
      ulcer region showed thick fibrous tissue without any atypical epithelial cells.
      The verrucous lesions were consistent with the diagnosis of eccrine
      syringofibroadenoma (ESFA). Moreover, an ESFA-like growth pattern was seen in the
      elevated margin of the ulcer. Our findings suggest that these lesions developed
      as a result of reactive eccrine duct hyperplasia followed by skin tissue
      remodelling.

PMID- 10971335
TI  - Xeroderma pigmentosum: the role of phototesting.
AB  - We report three patients newly diagnosed as having xeroderma pigmentosum (XP).
      Previous photobiological studies have implicated ultraviolet (UV) B as the
      activating waveband in XP, causing a delayed and prolonged erythemal response.
      This characteristic reaction pattern has been used as a quick screening test in
      patients suspected of having XP, while awaiting confirmatory DNA repair studies.
      Two of our patients showed no abnormal erythemal responses, and one showed severe
      photosensitivity from 330 to 400 nm but normal UVB responses, with a peak
      erythema at 24 h. We conclude that the erythemal responses in XP are highly
      variable and cannot be considered as a reliable screening test in the diagnosis
      of XP.

PMID- 10971336
TI  - Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical
      and HLA characteristics.
AB  - Although patients with both morphoea and lichen sclerosus have been reported
      previously, in the majority of these reports the lichen sclerosus has been
      extragenital. We report nine patients in whom genital lichen sclerosus coexisted
      with scleroderma spectrum disorders including seven with morphoea, one with
      morphoea and lichen planus, and one with systemic sclerosis. The clinical
      features, associated autoimmune disease, autoantibodies and HLA type are
      reported. Antibodies to Borrelia burgdorferi were not detected in any of the
      patients. The coexistence of these diseases raises a number of intriguing
      questions about the relationship between them.

PMID- 10971337
TI  - Development of squamous cell carcinoma by two high-risk human papillomaviruses
      (HPVs), a novel HPV-67 and HPV-31 from bowenoid papulosis.
AB  - We report a patient with bowenoid papulosis (BP) involving two high-risk human
      papillomaviruses (HPVs) and the development of invasive squamous cell carcinoma
      (SCC). Our patient showed verrucous lesions on the penis, perianal area and groin
      that had been noted over the previous 8 years and had recurred after all
      therapeutic approaches. The perianal and left inguinal lesions revealed invasive
      SCC on histology. HPV-31 and HPV-67 sequences were detected by polymerase chain
      reaction from BP lesions of the perianal area and the shaft of the penis. HPV-31
      has already been reported in BP as a high-risk HPV for the development of SCC,
      but HPV-67 is a novel one that has never been reported in BP. As HPV-67 has
      sequence homology to HPV-52 and HPV-58, it belongs to the family of HPV-16, a
      high-risk HPV group. Thus our patient showed two high-risk HPVs, i.e. HPV-31 and
      the novel HPV-67, which may be directly involved in the development of SCC.

PMID- 10971338
TI  - Bacillary angiomatosis on a region of burned skin in a immunocompetent patient.
AB  - Bacillary angiomatosis usually develops in immunodeficient patients with a
      history of contact with cats. We report a 21-year-old immunocompetent woman with
      facial angiomatous lesions following a second-degree burn and without a history
      of direct contact with cats. The diagnosis of bacillary angiomatosis was based on
      the demonstration of bacilli in histological sections stained by the Warthin
      Starry method. The lesions resolved 2 months after treatment with oral
      erythromycin for 8 weeks. This case emphasizes that bacillary angiomatosis may be
      seen in immunocompetent individuals and may be transmitted in other ways than cat
      scratches, e.g. by arthropods.

PMID- 10971339
TI  - Congenital hypotrichosis due to short anagen.
AB  - Two children with congenital hypotrichosis are described. Both presented with
      persistent short, fine hair since birth. Evidence is provided that the short hair
      observed in these patients is due to a short anagen phase of the hair cycle, with
      a normal rate of hair growth. Shortening of the anagen phase of the scalp hair
      cycle leads to a decrease in the maximal hair length and an increase in the
      number of hairs in telogen, resulting in an increase in hair shedding. Scanning
      electron microscopy showed a widely spaced cuticular pattern, a finding typically
      seen in hair of thin calibre. One patient had affected family members with an
      apparently autosomal dominant mode of inheritance. The disorder appears to
      resolve spontaneously during puberty and adulthood.

PMID- 10971340
TI  - Atypical fibroxanthoma of the skin and the lower lip in xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a rare, usually autosomal recessive disorder
      related to DNA repair defects. Atypical fibroxanthoma (AFX) is a pleomorphic
      tumour that occurs infrequently on the limbs and trunk in children. We report a
      child with XP who presented with AFX of the facial skin and the lower lip. The
      diagnosis of AFX was confirmed using histological and immunohistochemical
      techniques. We discuss the possibility that ultraviolet-induced damage might be
      implicated in the pathogenesis of AFX.

PMID- 10971341
TI  - A keratin 14 'knockout' mutation in recessive epidermolysis bullosa simplex
      resulting in less severe disease.
AB  - Epidermolysis bullosa simplex (EBS) is a blistering skin disease caused in most
      cases by mis-sense mutations in genes encoding the basal epidermal keratin (K) 5
      and K14. The inheritance is usually autosomal dominant and the mutant keratin
      proteins appear to exert a dominant negative effect on the keratin intermediate
      filament cytoskeleton in basal keratinocytes. We report a child with a homozygous
      K14 mutation resulting in the complete absence of K14 protein in the epidermis;
      remarkably, he only had mild to moderate disease. Electron microscopy of a skin
      biopsy showed a marked reduction in numbers of keratin intermediate filaments in
      the basal keratinocytes. Immunofluorescence microscopy using monoclonal antibody
      LL001 against K14 showed no staining, suggesting a functional knockout of K14.
      Sequence analysis of genomic DNA revealed a homozygous mutation in codon 31 of
      K14 that resulted in a premature stop codon further downstream in exon 1. The
      child's mother, who is unaffected by the disease, is heterozygous for the
      mutation. The consanguineous father was unaffected and unavailable for testing.
      The resulting mRNA is predicted to encode a protein of 116 amino acids, of which
      the first 30 are identical to the normal K14 sequence, and the remaining 86
      residues are mis-sense sequence. Four previously reported cases of autosomal
      recessive EBS with functional knockout of K14 were severely affected by
      blistering, in contrast to our patient in whom the predicted protein has only the
      first 30 amino acids of K14 and is therefore the closest to a true knockout of
      K14 protein yet identified.

PMID- 10971342
TI  - Progressive nodular histiocytosis accompanied by systemic disorders.
AB  - Progressive nodular histiocytosis is a proliferative process of histiocytes, the
      main element of which is the dermal dendrocyte. It is considered to form part of
      a group of histiocytic disorders related to juvenile xanthogranuloma, which also
      includes xanthoma disseminatum, benign cephalic histiocytosis, spindle cell
      xanthogranuloma and generalized eruptive histiocytosis; disorders which perhaps
      represent the spectrum of one single entity. We present the case of a 57-year-old
      man who, for 26 years, had had a progressively deforming process of cutaneous
      lesions, with systemic involvement, including chronic myeloid leukaemia,
      hepatosplenomegaly, hypothyroidism, hyperuricaemia and hypocholesterolaemia. We
      have not been able to establish precisely the relationship between these
      features.

PMID- 10971343
TI  - Cutaneous cryptococcus infection due to C. albidus associated with Sezary
      syndrome.
AB  - Cryptococcus albidus is a non-neoformans species of the genus Cryptococcus and is
      a rare cause of disease. There have been only 13 previously reported cases of
      systemic disease in which this opportunistic yeast has been isolated from the
      lung, cerebrospinal fluid and blood. We report the first case of cutaneous
      Cryptococcus infection due to the species C. albidus, in a man with Sezary
      syndrome.

PMID- 10971344
TI  - Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant
      melanosomes.
AB  - We report a Japanese man with Hermansky-Pudlak syndrome, having oculocutaneous
      albinism with a bleeding diathesis. Gene analysis of the patient's peripheral
      blood cells revealed that he was a compound heterozygote for HPS1 gene mutations.
      One of the mutations was a novel frameshift mutation at codon 321 (a G insertion)
      in exon 11 ( approximately 962-963insG), and the other was a 5' splice-junction
      mutation of IVS5 (IVS5 + 5G-->A). The content of eumelanin in the patient's hairs
      was significantly reduced. Histological analysis using light and electron
      microscopy revealed that melanocytes in the patient's epidermis contained an
      appreciable number of giant melanosomes. Cultured melanocytes from the patient's
      skin also contained giant melanosomes. Our finding of mutations in the HPS1 gene
      in relation to abnormalities in melanosome morphology and melanin production shed
      light on the role and function of the HPS1 gene product in the synthesis of
      melanosomes and melanin pigment.

PMID- 10971346
TI  - Verruca vulgaris following treatment of vitiligo with epidermal grafting.

PMID- 10971345
TI  - Hypereosinophilic syndrome presenting as cutaneous necrotizing eosinophilic
      vasculitis and Raynaud's phenomenon complicated by digital gangrene.
AB  - Cutaneous necrotizing eosinophilic vasculitis is a recently identified type of
      vasculitis that is characterized by an eosinophil-predominant necrotizing
      vasculitis affecting small dermal vessels. Clinically, it presents with pruritic
      erythematous and purpuric papules and plaques, peripheral eosinophilia and a good
      response to systemic steroid therapy. This vasculitis can be idiopathic or
      associated with connective tissue diseases. Although the pathogenic roles of
      eosinophil-derived granule proteins and interleukins have been documented in
      diseases associated with eosinophilia, a role of CD40 (a glycoprotein of the
      tumour necrosis factor receptor superfamily) has rarely been described. We
      describe two patients with idiopathic hypereosinophilic syndrome (HES) presenting
      with multiple erythematous patches and plaques on the lower extremities and
      Raynaud's phenomenon. They satisfied the criteria for the diagnosis of HES by
      clinical and laboratory investigations. Histopathology of the cutaneous lesions
      revealed prominent eosinophilic infiltration with local fibrinoid change in
      vessel walls in the dermis and subcutis. Immunohistochemical detection of CD3,
      CD4, CD8 and CD40 was performed. Infiltrating eosinophils were strongly stained
      by anti-CD40 monoclonal antibody. One patient improved with prednisolone,
      pentoxifylline and nifedipine, without recurrence. The other patient initially
      improved with steroids, but after self-withdrawal of steroid developed digital
      ischaemia that evolved to severe necrosis and required amputation. Cutaneous
      necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene
      may develop as cutaneous manifestations of HES. CD40 may play a part in the
      pathogenesis of eosinophilic vasculitis in HES.

PMID- 10971348
TI  - Paecilomyces marquandii cellulitis in a kidney transplant patient.

PMID- 10971347
TI  - Trichilemmal carcinoma with a cutaneous horn.

PMID- 10971349
TI  - Multicentric reticulohistiocytosis associated with Sjogren's syndrome.

PMID- 10971350
TI  - Recurrent self-healing cutaneous mucinosis in an adult.

PMID- 10971351
TI  - Localized morphoea, xanthomatosis and primary biliary cirrhosis.

PMID- 10971352
TI  - Unilateral resolution of palmar eczema and hyperhidrosis complicated by Horner's
      syndrome following ipsilateral endoscopic cervical sympathectomy.

PMID- 10971353
TI  - Management difficulties due to concurrent dermatitis herpetiformis and variegate
      porphyria.

PMID- 10971354
TI  - Giant combined dermatofibroma.

PMID- 10971355
TI  - Grover's disease, despite histological similarity to Darier's disease, does not
      share an abnormality in the ATP2A2 gene.

PMID- 10971356
TI  - Intranasal buserelin acetate-induced pigmented roseola-like eruption.

PMID- 10971357
TI  - A case of chronic granulomatous skin disease associated with deficient HLA class
      I expression.

PMID- 10971358
TI  - Human herpesvirus type 8-positive facial angiosarcoma developing at the site of
      botulinum toxin injection for blepharospasm.

PMID- 10971359
TI  - Adaptive antioxidant defence in human dermal fibroblasts.

PMID- 10971360
TI  - Codeine caused pruritic scarlatiniform exanthemata: patch test negative but
      positive to oral provocation test.

PMID- 10971361
TI  - Partial lipodystrophy with hemithoracic atrophy.

PMID- 10971362
TI  - CD56 and terminal deoxynucleotidyl transferase positive cutaneous lymphoblastic
      lymphoma.

PMID- 10971363
TI  - Severe disabling Koebnerizing ulcerated necrobiosis lipoidica successfully
      managed with topical PUVA.

PMID- 10971364
TI  - Granuloma pyogenicum arising in an arteriovenous haemangioma associated with a
      port-wine stain.

PMID- 10971365
TI  - Dermatomyositis with the features of inclusion body myositis associated with
      carcinoma of the bladder: a true association?

PMID- 10971366
TI  - Chronic ulcerative stomatitis: antibodies reacting with the 70-kDa molecule react
      with epithelial nuclei.

PMID- 10971367
TI  - Wells' syndrome and human immunodeficiency virus infection.

PMID- 10971368
TI  - Photodistributed telangiectasia following use of cefotaxime.

PMID- 10971369
TI  - Hypereosinophilic dermatosis: skin lesions as the only manifestation of the
      idiopathic hypereosinophilic syndrome?

PMID- 10971370
TI  - Blue rubber bleb naevus syndrome: an unusual cause of urethral bleeding.

PMID- 10971371
TI  - Progressive nodular histiocytomas.

PMID- 10971372
TI  - Periorbital heliotrope oedema as the only initial clinical manifestation of
      systemic lupus erythematosus in a primigravida.

PMID- 10971373
TI  - Pyemotes dermatitis caused by indirect contact with husk rice.

PMID- 10971374
TI  - Oral terbinafine treatment for toenail onychomycosis: follow-up after 5-6 years.

PMID- 10971375
TI  - Pneumocystis carinii pneumonia in a patient with pyoderma gangrenosum treated
      with cyclosporin.

PMID- 10971376
TI  - Peripheral neuropathy as the first manifestation of Madelung's disease.

PMID- 10971377
TI  - Haemangioma of the head and neck with subglottic involvement and atypical
      coarctation.

PMID- 10971378
TI  - Histological changes in naevi with superimposed psoriasis.

PMID- 10971379
TI  - Detection of translocation (16;16) in acute myeloid leukaemia (AML) patients by
      fluorescence in situ hybridization (FISH) using 16 telomer's probes.

PMID- 10971380
TI  - History of tissue factor.

PMID- 10971382
TI  - Towards a targeted, risk-based, antifungal strategy in neutropenic patients.

PMID- 10971381
TI  - Leucocyte depletion of the blood supply - how will patients benefit?

PMID- 10971383
TI  - Can multidrug resistance mechanisms be modified?

PMID- 10971384
TI  - Prospective evaluation of oral mucositis in patients receiving myeloablative
      conditioning regimens and haemopoietic progenitor rescue.
AB  - Four hundred and twenty-nine patients received myeloablative chemotherapy for
      solid and haematological malignancies in a bone marrow transplantation unit.
      Regimens appropriate to the tumour type were administered and haemopoietic
      reconstitution was achieved with peripheral blood progenitor cells (PBPC; n =
      275), autologous bone marrow (auto-BMT; n = 69) or allogeneic bone marrow (allo
      BMT; n = 85). World Health Organization (WHO) oral mucositis scores were
      collected prospectively from the start of chemotherapy (d 1) until d 28 or
      discharge. Oral mucositis (OM) was experienced by 425 (99%) patients and in 289
      (67.4%) this was grade III or IV. Strong opiate analgesia was prescribed for a
      median of 6 d to 47% of patients. Univariate analysis suggested that the area
      under the OM curve (AUC; sum of daily mucositis grades, d 1-28) was associated
      with the myeloablative regimen, haemopoietic progenitor source (PBPC > allo-BMT >
      auto-BMT), use of myeloid growth factors and age. Multivariate analysis showed
      that the only independent risk factor for mucositis was the conditioning regimen
      (P < 0.00005). The mean OM AUC for high-dose melphalan (HDM) regimens (52 grade
      days) exceeded busulphan (41), busulphan-cyclophosphamide (35), cyclophosphamide
      total body irradiation (TBI) (34), cyclophosphamide-carmustine (BCNU) (20) and
      cyclophosphamide-etoposide-carmustine (CVB) (19). HDM regimens resulted in the
      highest mean peak OM (3.6), followed by busulphan regimens (2.6),
      cyclophosphamide/TBI (2.3) and cyclophosphamide-carmustine and CVB (1.4).
      Busulphan produced significantly delayed OM (median 3 d; P < 0.00005). There was
      a linear association between the area under the OM curve for each treatment group
      and the time to reach grade 3 OM (P < 0.00005), but no association with the time
      to reach grade 4 neutropenia (P = 0.24) or thrombocytopenia (P = 0.73), implying
      that haematological and mucosal toxicity are not associated. The cytotoxic
      regimen is the most significant determinant of OM. Studies investigating agents
      to ameliorate mucosal toxicity should be stratified according to cytotoxic
      regimen.

PMID- 10971385
TI  - Amifostine can reduce mucosal damage after high-dose melphalan conditioning for
      peripheral blood progenitor cellautotransplant: a retrospective study.
AB  - Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role
      in preventing extrahaematological toxicity after high-dose therapy (HDT) has
      never been investigated. We compared two historical groups of patients who either
      received (group A, n = 35) or did not receive (group B, n = 33) amifostine (740
      mg/m2) before high-dose (HD) melphalan, followed by autologous infusion of
      peripheral blood progenitor cells (PBPCs). Amifostine was well tolerated at this
      dose level. Emesis grade 1-2 was the most important side-effect, but the
      interruption of infusion was never required. The incidence and median duration of
      severe mucositis (grade 3-4) was 21% and 0 d (range 0-11 d) in group A and 53%
      and 7 d (range 0-11 d) in group B. The duration of analgesic therapy was also
      significantly lower in group A (0 d; range 0-12) than in group B (6 d, range 0
      20) (P = 0.0001). Severe diarrhoea (3% vs. 25%; P = 0.01) and emesis (9% vs. 34%;
      P = 0.01) were also reduced in group A in comparison with group B. No differences
      were observed between the two groups for haematological recovery. This
      retrospective study strongly suggests that amifostine can reduce severe mucositis
      and the use of analgesic drugs in this setting. A randomized study is warranted
      to confirm these preliminary results.

PMID- 10971386
TI  - No impact of high-dose cytarabine on the outcome of patients transplanted for
      acute myeloblastic leukaemia in first remission. Acute Leukaemia Working Party of
      the European Group for Blood and Marrow Transplantation (EBMT).
AB  - High-dose cytarabine is currently used in combination with anthracycline in the
      treatment of acute myeloblastic leukaemia (AML). Moreover, high-dose cytarabine
      has been reported to produce long-term disease-free survival in a proportion of
      patients, especially in certain subtypes of AML. However, it remains unknown
      whether the outcome of patients undergoing allogeneic or autologous stem cell
      transplantation is influenced by previous treatment with high-dose cytarabine. To
      this end, 1672 patients with AML in first remission who were reported to the
      Acute Leukaemia Working Party registry of the European Group for Blood and Marrow
      Transplantation (EBMT) and who were transplanted between 1980 and 1995 were
      analysed according to the dose intensity of cytarabine given at induction and/or
      consolidation. Autologous stem cell transplantation (ABMT) was performed in 846
      patients and allogeneic bone marrow transplantation (BMT) in 826 patients. This
      study shows that the dose of cytarabine (Ara-C) given at induction and/or
      consolidation did not influence the relapse incidence in patients subsequently
      allografted or autografted. In addition, it did not give any advantage in terms
      of overall outcome. Therefore, high-dose (HD) Ara-C may not be needed for
      patients who have a planned stem cell transplantation (SCT) as post-remission
      therapy. Nevertheless, HD Ara-C may be utilized in certain subtypes of AML that
      are believed to be curable by chemotherapy alone.

PMID- 10971387
TI  - Functional analysis of the CD8+CD57+ cell population in normal healthy
      individuals and matched unrelated T-cell-depleted bone marrow transplant
      recipients.
AB  - The biological activities of CD8+ that co-express CD57 remain poorly defined. It
      is unclear whether all CD8+ cells have the potential to become CD57+ or whether
      they represent a unique subset with distinct functions. Several studies have
      reported the association between elevated numbers of CD8+CD57+ and a wide range
      of clinical disorders such as viral reactivation of human cytomegalovirus (HCMV).
      In this study, we have investigated the relationship between viral reactivation
      and the effect of diminished interleukin (IL)-2 production. Using CD8+ cells
      isolated from patients at various times after allogeneic transplants and in vitro
      models of HCMV infection, we determined their combined effect on CD8+CD57+. Our
      results show that high numbers of CD8+CD57+ correlated with diminished killing of
      HCMV-infected targets. In addition, we showed a synergistic effect between IL-2
      and HCMV in the expansion of CD8+CD57+ cells. Furthermore, these cells after anti
      CD3 stimulation did not produce tumour necrosis factor (TNF)-alpha or interferon
      (IFN)-gamma. Interestingly, IL-10 production was elevated in several patients
      which appeared to be associated with the time from transplant.

PMID- 10971388
TI  - Determination of helper T-cell precursor frequencies against non-haemopoietic
      cells: comparison of co-stimulation provided by anti-CD28 antibody versus the
      cellular ligand B7-1.
AB  - Helper T-cell precursor frequency assays (HTLp-assays) are commonly used in
      transplantation to examine the frequency of T cells reactive against donor or
      host alloantigens. In these assays, peripheral blood mononuclear cells (PBMCs)
      are most often used as stimulator cells. However, cells targeted after
      transplantation do not always belong to the haematopoietic lineage and may
      express different alloantigens, especially minor histocompatibility antigens
      (mHags). Non-haematopoietic cells lack expression of the B7 co-stimulatory
      molecules needed to activate primary T cells that can be supplied by anti-CD28
      (alphaCD28) antibodies or transfection with B7-1 coding sequences. At present, it
      is not known how these two ways of supplied co-stimulation compare in HTLp
      assays. B7-1-transfected A431 keratinocytes (A431B7-1) induced higher
      proliferative responses in allogeneic primary T cells and more interleukin (IL) 2
      production than that induced by A431 cells plus alphaCD28, whereas the kinetics
      of proliferation and IL-2 production were similar. Neither cross-linking of
      alphaCD28 bound to T cells nor prevention of IL-2 resorption by the anti-IL-2
      receptor resulted in improved proliferation or IL-2 production. Results of HTLp
      assays indicated that A431B7-1 activated on average 7.5 times more alloreactive
      IL-2-producing T cells than A431 cells plus alphaCD28. We conclude that primary T
      cell alloresponses against major histocompatibility complexes (MHCs) and mHags
      expressed on non-haematopoietic cells can be measured in HTLp assays using
      supplied co-stimulation, although alphaCD28 yields an intrinsic underestimation
      of actual frequencies.

PMID- 10971389
TI  - Interleukin 6 receptor expression by human cord blood- or peripheral blood
      derived primitive haematopoietic progenitors implies acquisition of different
      functional properties.
AB  - The significance of interleukin 6 receptor (IL-6R) expression by cord blood (CB)-
      and peripheral blood (PB)-derived primitive haematopoietic progenitors was
      investigated. IL-6R was preferentially expressed by PB-derived myeloid
      progenitors. Most PB-derived erythroid bursts (BFU-E) and mixed colony-forming
      cells (CFU-Mix) did not express this receptor. However, CB-derived primitive
      progenitor cells possessed multipotentiality, irrespective of IL-6R expression.
      Interestingly, the long-term culture-initiating cell (LTC-IC) population was
      enriched in PB-derived CD34+ IL-6R+ cells, but the extended LTC-IC (ELTC-IC)
      population, which represents a less mature class of haematopoietic progenitors,
      seemed to be equally distributed in the IL-6R+ and IL-6R- cell populations. In
      contrast, the number of LTC-ICs and ELTC-ICs was similar in CB-derived CD34+ IL
      6R+ or IL-6R- cells. It is noteworthy that the number of LTC-ICs and ELTC-ICs in
      CB-derived CD34+ cells was markedly higher than that in PB-derived CD34+ cells
      regardless of IL-6R expression. Telomerase activity was consistently lower in PB
      derived CD34+ IL-6R- cells than in CD34+ IL-6R+ cells. In contrast, telomerase
      activity was similar in CB-derived CD34+ IL-6R+ or IL-6R- cells. The pattern of
      telomerase induction upon cytokine stimulation differed between CB- and PB
      derived CD34+ IL-6R+ or IL-6R- cells. However, overall telomerase activity per
      dish was well correlated with the proliferative potential of both cell
      populations, suggesting that induction of telomerase plays an important role in
      the escape from replicative senescence of primitive haematopoietic progenitors.
      Collectively, these results suggest that CB-derived primitive progenitors are
      less mature than PB-derived progenitors and that the expression of IL-6R by
      primitive haematopoietic progenitors may have different implications for PB- and
      CB-derived CD34+ cells.

PMID- 10971390
TI  - Effective treatment of Jo-1-associated polymyositis with T-cell-depleted
      autologous peripheral blood stem cell transplantation.
AB  - A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky
      score of 40% and severe muscle, liver and lung damage that was refractory to
      standard therapy. The female patient received an autologous T-cell-depleted
      haematopoietic stem cell transplant (HSCT) after myeloablative conditioning. The
      transplant procedure was complicated by severe adult respiratory distress
      syndrome (ARDS) and adenovirus-associated haemorrhagic cystitis as well as
      cytomegalovirus (CMV) reactivation. The patient's creatinine phosphokinase (CPK)
      and alanine transaminase (ALT) values were normal on day 21. The patient's
      strength has improved remarkably and her dyspnoea is subjectively improved. At 15
      months after the transplant, the patient was well with a Karnofsky score of 80%
      and had been off any therapy, including steroids, for 14 months.

PMID- 10971391
TI  - Mapping of leukaemia-associated breakpoints in chromosome band 3q21 using a newly
      established PAC contig.
AB  - Chromosome aberrations affecting band 3q21 are associated with a particularly
      poor prognosis in patients with acute myeloid leukaemia. To facilitate the
      molecular characterization of such rearrangements, we established a PAC contig
      covering the relevant genomic region. Using these PACs as probes in fluorescence
      in situ hybridization (FISH) experiments, we showed that a number of 3q21
      breakpoints in patient samples map to a previously defined 'breakpoint cluster
      region'. Others, however, are located at varying distances centromeric of it.
      These results have important implications in the search for genes affected by
      3q21 rearrangements.

PMID- 10971392
TI  - In vitro anti-tumour activity of anti-CD80 and anti-CD86 immunotoxins containing
      type 1 ribosome-inactivating proteins.
AB  - Immunotoxins specific for the CD80 and CD86 antigens were prepared by linking
      three type 1 ribosome-inactivating proteins (RIPs), namely bouganin, gelonin and
      saporin-S6, to the monoclonal antibodies M24 (anti-CD80) and 1G10 (anti-CD86).
      These immunotoxins showed a specific cytotoxicity for the CD80/CD86-expressing
      cell lines Raji and L428. The immunotoxins inhibited protein synthesis by target
      cells with IC50s (concentration causing 50% inhibition) ranging from 0.25 to 192
      pmol/l as RIPs. The anti-CD80 immunotoxins appeared 1-2 log more toxic for target
      cells than the anti-CD86 ones. Immunotoxins containing saporin and bouganin
      induced apoptosis of target cells. The toxicity for bone marrow haemopoietic
      progenitors of these conjugates was also evaluated. Bouganin and related
      immunotoxins at concentrations up to 100 nmol/l did not significantly affect the
      recovery of committed progenitors or of more primitive cells. The saporin
      containing immunotoxins at concentrations >/= 1 nmol/l showed some toxicity on
      colony-forming unit cells (CFU-C). The expression of the CD80 and CD86 molecules
      is prevalently restricted to antigen-presenting cells and is also strong on
      Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Present results suggest
      that immunotoxins targeting type 1 ribosome-inactivating proteins to these
      antigens could be considered and further studied for the therapy of Hodgkin's
      disease or other CD80/CD86-expressing tumours.

PMID- 10971393
TI  - Lack of interferon-alpha-induced tyrosine phosphorylation of Vav proto-oncogene
      in patients with myelofibrosis with myeloid metaplasia.
AB  - Myelofibrosis with myeloid metaplasia (MMM) is an uncommon chronic
      myeloproliferative disorder characterized by clonal stem cell proliferation and
      reactive non-clonal proliferation of bone marrow fibroblasts with fibrosis. In
      the absence of curative therapy, the current management for the majority of
      patients is directed towards alleviation of symptoms and improvement in quality
      of life. A number of experimental therapies have been investigated, among which
      is the use of type I interferon (IFN)-alpha, whose overall results are
      disappointing. We recently showed that the Vav proto-oncogene product, p95Vav,
      which is phosphorylated under IFN-alpha treatment, associates with both chains
      that constitute the functional type I IFN receptor and contributes to the
      antiproliferative effects of IFN-alpha. The involvement of p95Vav in IFN-alpha
      signalling and the frequent non-responsiveness of patients to IFN-alpha led us to
      investigate for any functional defect(s) of Vav in response to IFN in MMM
      patients. Our results showed that in the majority of patients Vav is
      constitutively hyperphosphorylated and that IFN-alpha failed to increase
      substantially such a tyrosine phosphorylation of p95Vav.

PMID- 10971394
TI  - Significance of lung resistance-related protein in the clinical outcome of acute
      leukaemic patients with reference to P-glycoprotein.
AB  - Lung resistance-related protein (LRP) overexpression in leukaemic blast cells
      from acute leukaemia patients and the effect of LRP or P-glycoprotein (P-gp) on
      the clinical outcome of acute leukaemia were investigated individually by
      dividing patients into four groups. The complete remission rate of group I (LRP
      and P-gp both negative) was 81.7%, group II (only LRP positive) 87.5%, group III
      (only P-gp positive) 87.1% and group IV (LRP and P-gp both positive) 40.0%. There
      were no statistical differences between group I and groups II or III, but a
      significant difference was observed between groups I, II or III and group IV.
      Median overall survival in group IV was significantly shorter (4.6 months) than
      in groups I, II or III, although no significant differences were observed between
      group I and groups II or III (18.9, 20.5 and 31.8 months). There was a tendency
      for disease-free survival in group III to be longer than that in groups I, II or
      IV. The reasons for these findings are discussed. Our present results indicate
      that the co-existence of LRP and P-gp strongly influenced the effectiveness of
      induction chemotherapy and long-term prognosis, whereas the isolated presence of
      LRP or P-gp did not.

PMID- 10971396
TI  - Surface expression of HLA-DM on dendritic cells derived from CD34-positive bone
      marrow haematopoietic stem cells.
AB  - HLA-DM has been known to be largely absent from the cell surface of antigen
      presenting cells, accumulating instead in the intracellular compartment. In this
      study, we demonstrated that a population of HLA-DM-positive (HLA-DM+) dendritic
      cells (DCs) can be identified in an in vitro culture of CD34+ bone marrow
      haematopoietic stem cells. CD34+ bone marrow cells of healthy donors were used to
      generate DCs with the recombinant human cytokines granulocyte-macrophage colony
      stimulating factor (GM-CSF), tumour necrosis factor alpha (TNF-alpha) and stem
      cell factor (SCF), both with and without interleukin 4 (IL-4). Flow cytometric
      analysis demonstrated that HLA-DM+ cells comprised 2.5 +/- 0.9% and 1.8 +/- 0.4%
      of the CD34+ cell-derived progeny in the presence of GM-CSF, TNF-alpha and SCF
      after 7 d and 14 d of culture respectively. The number of HLA-DM molecules
      expressed per HLA-DM+ cell on d 7 was significantly higher than that on d 14
      (1410 +/- 47 versus 370 +/- 25, P < 0.05). The addition of IL-4 to the cytokines
      from the commencement of culture increased the proportion of HLA-DM+ cells and
      increased the number of HLA-DM molecules per HLA-DM+ cell significantly (P <
      0.05). Although most of the HLA-DM+ cells expressed CD1a, CD80 or CD86 antigen,
      only a small proportion of CD1a+, CD80+ or CD86+ cells expressed HLA-DM. About
      half the HLA-DM+ cells expressed CD83. The addition of IL-4 resulted in a
      decrease in the expression of CD83 on the HLA-DM+ cells on d 7. Microscopic
      evaluations of sorted HLA-DM+ cells revealed the characteristic morphological
      features of DCs. Primary mixed lymphocyte cultures demonstrated that the HLA-DM+
      cells elicited a vigorous proliferation of allogeneic T cells. The level of
      antigen-specific T-cell activation induced by antigen-pulsed, chloroquine-treated
      HLA-DM+ cells was substantially higher than that induced by HLA-DM- cells (P <
      0.05). These results show that HLA-DM can be used as a useful DC lineage-specific
      marker, as well as a tool for the characterization of DCs and human
      immunotherapy.

PMID- 10971395
TI  - Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in
      reinduction according to the ALL/NHL-BFM 95 protocols.
AB  - Hypersensitivity reactions are relevant adverse effects of asparaginase therapy.
      Therefore, children treated with native Escherichia coli asparaginase in
      induction therapy of acute lymphoblastic leukaemia (ALL) or non-Hodgkin's
      lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug
      monitoring. Seventy children, including four patients with allergic reactions
      during induction, were given one dose of Oncaspar 1,000 U/m2 intravenously.
      Activity was determined every third or fourth day until it dropped below the
      limit of quantification. In current reinduction protocols [ALL/NHL-Berlin
      Frankfurt-Munster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli
      asparaginase deplete asparagine for about 2-3 weeks, therefore activities of >/=
      100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients
      without an allergic reaction during induction, the mean activity was 606 +/- 313
      U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In
      44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity
      was seen in the remaining 22 patients, including 8/22 patients who showed no
      activity after 1 week. Toxicity was low and comparable to the native enzymes but,
      in contrast to about 30% of hypersensitivity reactions with conventional
      reinduction therapy, no allergic reaction was seen. Substituting 4 x 10,000 U/m2
      asparaginase medac for one dose of 1,000 U/m2 Oncaspar was safe and well
      tolerated. Comparable pharmacokinetic treatment intensity was achieved in about
      two-thirds of patients.

PMID- 10971397
TI  - Ferritin expression in maturing normal human erythroid precursors.
AB  - We studied the expression of H- and L-ferritin subunits at sequential stages of
      maturation of normal human erythroid precursors. The erythroid cells developed in
      liquid culture and were purified immunomagnetically before analysis. It was found
      that the content of both ferritin subunits decreased exponentially with
      maturation: the decrease was rapid when cellular haemoglobin was low, and it
      slowed down when the haemoglobin was increased. This mode of decline was
      especially pronounced for the L-subunits. The H-/L-subunit ratio did not change
      significantly during the investigated period. The synthesis of both subunits was
      equal at each given developmental stage, and declined significantly with
      maturation. However, this decline was just slightly faster than that of total
      protein synthesis. The data indicated that the degradation of H- and L-ferritin
      also declined as maturation proceeded. No decrease was observed in mRNA levels of
      either ferritin subunit. Thus, the ferritin content and turnover were maximal at
      the beginning of haemoglobin accumulation and diminished later. As the rate of
      ferritin turnover determines the rate of incorporation and release of its iron,
      the results presented suggest that ferritin mediates cellular iron transport and
      donates iron for haem synthesis, mainly at the beginning of haemoglobin
      accumulation. The synthesis of both ferritin subunits is regulated during
      erythroid maturation at the post-transcriptional level.

PMID- 10971398
TI  - Evidence for two alternatively spliced forms of phospholipase C-beta2 in
      haematopoietic cells.
AB  - Alternatively spliced forms have been reported for several phospholipase C (PLC)
      isozymes, but not for PLC-beta2, the most abundant PLC-beta in platelets. PLC
      beta2 cDNA cloned from the HL-60-cell cDNA library is 3543 bases long, coding for
      1181 amino acids. Compared with the published sequence, a deletion of 45
      nucleotides (2755-2799 nt, amino acids 864-878) was detected in platelet and
      leucocyte mRNA amplified by reverse transcription (RT) polymerase chain reaction
      (PCR) using primers corresponding to 1814-1838 nt (forward) and 3328-3352 nt
      (reverse). Amplification of genomic DNA using primers corresponding to 2575-2596
      nt and 2864-2885 nt yielded a approximately 750 bp product; restriction analysis
      and sequencing revealed the 45-bp exon flanked by introns of 198 bp and 118 bp.
      Amplification of leucocyte and platelet cDNA using the same primers yielded
      products of approximately 310 nt and approximately 265 nt, with (PLC-beta2a) and
      without (PLC-beta2b) the 45-nt sequence. Thus, two alternatively spliced forms
      (1181 and 1166 amino acids) of PLC-beta2 are generated in haematopoietic cells.
      They differ in the carboxyl terminal sequence implicated in interaction of PLC
      beta enzymes with Galphaq, particulate association and nuclear localization. We
      propose that the PLC-beta2 splice variants may be regulated differentially with
      distinct roles in signal transduction.

PMID- 10971399
TI  - Kell is not restricted to the erythropoietic lineage but is also expressed on
      myeloid progenitor cells.
AB  - Anti-Kell antibodies have been shown to suppress fetal erythropoiesis, but little
      is known about their effect on myelopoiesis. We analysed the effect of Kell
      related antibodies on granulocyte-macrophage colony-forming units (CFU-GM) growth
      in semisolid medium using peripheral blood mononuclear cells (PBMNCs) from
      haematologically normal individuals. In addition to its inhibitory effect on
      erythroid burst-forming units (BFU-E) growth, anti-Kell antibodies significantly
      reduced CFU-GM colony formation from Kell-positive individuals but not from Kell
      negative donors. Moreover, anti-cellano and anti-Kpb antibodies also inhibited
      the growth of CFU-GM from antigen-positive MNCs. These data indicate that Kell is
      not restricted to erythroid blood cells, but is also expressed on myeloid
      progenitor cells.

PMID- 10971400
TI  - Effect of nitric oxide and nitric oxide donors on red blood cell oxygen
      transport.
AB  - A mechanism has been proposed in which nitric oxide (NO) may bind to cysteine
      beta93 and be transported by haemoglobin from the lungs to the tissues and modify
      vascular tone. In addition, it has been reported that treatment of sickle cell
      anaemia blood with 80 p.p.m. NO gas in air shifts the oxygen affinity, as
      measured by P50 to the left. We exposed normal and sickle cell anaemia blood to
      80 p.p.m. NO in air for 1 h in vitro and found no change in P50 of either normal
      or sickle cell blood. In addition, we exposed normal and sickle cell blood in
      buffer to aqueous NO (NO gas dissolved in buffer) at varying concentrations and
      found that the induced left shift in P50 correlates strongly and linearly with
      methaemoglobin formation. We also treated normal and sickle cell blood with other
      nitric oxide donors, such as sodium 2-(N, N-diethylamino)-diazenolate-2-oxide
      (DEANO), S-nitrosocysteine (CysNO) and sodium trioxodinitrate (OXINO, or Angeli's
      salt). In all cases, we found a dose-dependent increase in methaemoglobin that
      was strongly correlated with the dose-dependent P50 reduction. Our data do not
      support the report that low NO concentrations can selectively increase the oxygen
      affinity of sickle cell blood without affecting methaemoglobin levels
      significantly. NO, however, may have benefit in sickle cell disease by other
      mechanisms.

PMID- 10971401
TI  - Severe congenital dyserythropoietic anaemia type I: prenatal management,
      transfusion support and alpha-interferon therapy.
AB  - We report a case of congenital dyserythropoietic anaemia, type I, with severe pre
      and postnatal manifestations. Exchange transfusions were required for fetal
      anaemia (3.5 g/dl) at 28 and 30 weeks of gestation. Transfusions were
      administered at birth (Caesarean section at week 35) and at regular intervals
      thereafter. At 14 months, alpha-interferon therapy was initiated (106 units three
      times a week). This resulted in stabilization of the haemoglobin at or above 11
      g/dl and a reduction in the percentage of erythroblasts with ultrastructurally
      abnormal heterochromatin. After 9 months, the dose of alpha-interferon was
      decreased to 106 units twice a week. No relapse of anaemia was noted during an
      additional 4 months of follow-up.

PMID- 10971402
TI  - Lymphocyte function antigen 1 (LFA-1) mediates early tumour necrosis factor alpha
      induced leucocyte adhesion in venules.
AB  - A co-ordinated expression of specific adhesion molecules regulates leucocyte
      endothelium interactions in the microcirculation. In the present study, we used
      intravital microscopy of the cremaster muscle in CD11a gene-targeted mice to
      examine the role of lymphocyte function antigen 1 (LFA-1, CD11a/CD18) in tumour
      necrosis factor alpha (TNF-alpha)-induced leucocyte rolling and firm adhesion in
      venules. We found that 30 min after TNF-alpha administration leucocyte rolling
      was unchanged compared with phosphate-buffered saline (PBS)-treated mice and
      similar in LFA-1-deficient and wild-type animals. In contrast, firm leucocyte
      adhesion in venules increased by almost 10-fold following 30 min of TNF-alpha
      challenge in LFA-1-expressing animals, whereas no increase was observed in LFA-1
      deficient mice. Four hours after intrascrotal administration of TNF-alpha,
      venular leucocyte adhesion was found to be markedly increased, but similar in
      extent to LFA-1-deficient and wild-type mice. Histological examination of
      haematoxylin-eosin-stained tissue sections revealed that approximately 90% of the
      leucocytes in the TNF-alpha-stimulated venules in both wild-type and LFA-1
      deficient mice were polymorphonuclear. Taken together, our functional in vivo
      data demonstrate that LFA-1 is an important adhesion molecule in early TNF-alpha
      induced venular leucocyte adhesion.

PMID- 10971403
TI  - An unusual form of persistent polyclonal B lymphocytosis in an infant.
AB  - We report a case of persistent polyclonal lymphocytosis in an infant. The
      circulating lymphocytes were of a small to medium size and a small proportion
      were larger and had lymphoplasmacytoid features. The presence of either an
      infectious or mutagenic agent was excluded. The polyclonal B-cell nature of the
      lymphocyte was demonstrated by immunological markers and confirmed by Southern
      blot analysis and by polymerase chain reaction targeting immunoglobulin genes. In
      contrast to the common form of polyclonal lymphocytosis, this case was not
      associated with HLA-DR7 and/or abnormalities of chromosome 3, p53 or Bcl2/IgH.
      Whether this lymphocytosis represents a premalignant or a benign condition
      remains uncertain, although there has been no progression to date.

PMID- 10971404
TI  - Restriction of T-cell receptor repertoires in idiopathic CD4+ lymphocytopenia.
AB  - We report that alpha/beta and gamma/delta T-cell repertoires of three patients
      with idiopathic CD4+ lymphocytopenia, who showed different clinical
      manifestations and outcomes over time, were highly restricted. The disruption of
      T-cell repertoires does not influence the susceptibility to infections: the first
      patient was unable to attain a protective response to mycobacterium, the second
      showed clinical improvement and the third did not develop opportunistic
      infections. These results indicate that idiopathic CD4+ lymphocytopenia could
      give rise to mono-/oligoclonal T-cell expansions, but the degree of repertoire
      disturbance is not indicative of the severity of disease progression.

PMID- 10971405
TI  - Hereditary cyclic neutropenia in the male members of a Chinese family with
      inverted Y chromosome.
AB  - We describe four male members of a Chinese family, including the father and three
      sons, with hereditary cyclic neutropenia. These patients had all developed cyclic
      neutropenia in childhood with a cycle of around 21 d. Recurrent mucosa and skin
      infections with fever had occurred frequently, but gradually decreased in
      severity on reaching adulthood. Monocytosis was found during the neutrophil
      nadirs in all four patients. Mildly increased serum immunoglobulin (Ig)A and IgG
      levels, low levels of serum stem cell factor, as well as decreased sperm count
      and motility were demonstrated in the two elder sons. Chromosomal analysis showed
      a pericentric inversion of Y chromosome [46,X, inv(Y)(p11.2;q11.23)] in all of
      the men. These findings may suggest an association between cyclic neutropenia
      with oligospermia and inv(Y)(p11.2;q11.23) in this particular family.

PMID- 10971406
TI  - Mutations in the thrombopoietin receptor, Mpl, in children with congenital
      amegakaryocytic thrombocytopenia.
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder of
      undefined aetiology. The disease presents with severe thrombocytopenia and
      absence of megakaryocytes in the bone marrow. Furthermore, CAMT patients may
      develop bone marrow aplasia. To obtain more insight into the mechanism underlying
      CAMT, five children were analysed. All patients had increased plasma
      thrombopoietin (Tpo) levels, indicating a platelet production defect. Bone marrow
      derived CD34+ stem cells from three patients were cultured in an in vitro liquid
      culture system to study megakaryocytopoiesis. CD34+ cells from two of the three
      patients failed to differentiate into megakaryocytes. The lack of megakaryocyte
      formation could imply that a defect in the c-mpl gene, encoding the Tpo receptor,
      exists. Sequencing of c-mpl revealed mutations in four of five patients. Three
      patients had point mutations and/or a deletion in the coding regions of c-mpl.
      All point mutations led to an amino acid substitution or to a premature stop
      codon. In one patient, a homozygous mutation in the last base of intron 10 was
      found that resulted in loss of a splice site. This study showed that mutations in
      c-mpl could be the cause of thrombocytopenia in CAMT in the majority of patients.
      Furthermore, Tpo has been shown to have an anti-apoptotic effect on stem cells.
      Therefore, mutations in c-mpl might not only affect megakaryocyte formation but
      may also impair stem cell survival, which could explain the occurrence of bone
      marrow failure as final outcome in patients with CAMT.

PMID- 10971407
TI  - Dose-response relationship of megakaryocyte progenitors from the bone marrow of
      thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin.
AB  - Megakaryocyte (MK) progenitors from the marrow of adults undergo dose-dependent
      clonogenic proliferation in response to recombinant thrombopoietin (rTpo). It is
      unknown whether progenitors from the marrow of thrombocytopenic neonates display
      rTpo dose-dependent proliferation and whether they are more or less sensitive to
      rTpo than progenitors from non-thrombocytopenic neonates or adults. To assess
      this, we cultured marrow from four thrombocytopenic and four non-thrombocytopenic
      neonates, and from six healthy adults, in a serum-free system in the presence of
      increasing concentrations of rTpo (0-100 ng/ml). Marrow from the thrombocytopenic
      and non-thrombocytopenic neonates generated three times more MK colonies/105
      light density cells (129 +/- 39 and 167 +/- 30 respectively) than marrow from
      adults (54 +/- 30, P < 0.0001) at a rTpo concentration of 50 ng/ml. Neonatal and
      adult samples had a rTpo dose-dependent increase in MK colonies. However,
      neonates reached a maximal number of colonies at a rTpo concentration of 10
      ng/ml, compared with 50 ng/ml in adults, resulting in a larger area under the
      rTpo dose-response curve for neonatal progenitors (P = 0. 0047). Neonates also
      generated more large MK colonies than the adults (24% vs. 2% at 100 ng/ml).

PMID- 10971408
TI  - Bleeding symptoms and coagulation abnormalities in 337 patients with AL
      amyloidosis.
AB  - Haemorrhage is a frequent manifestation of amyloidosis. We performed a
      retrospective clinical analysis of 337 patients with systemic immunoglobulin
      light-chain (AL)-amyloidosis, in whom whole-body serum amyloid P component (SAP)
      scintigraphy and a clotting screen had been performed. Abnormal bleeding was
      noted in 94 cases (28%), and the coagulation screen was abnormal in 172 cases
      (51%). The most common abnormalities were prolongation of the thrombin time (TT;
      108 cases, 32%) and the prothrombin time (PT; 82 cases, 24%). In multivariate
      analysis, a prolonged PT was the only coagulation abnormality associated with
      abnormal bleeding (P = 0.0012), but this was independent of the whole-body
      amyloid load. Prolongation of the TT was associated with hepatic amyloid
      infiltration (P < 0.00001), with proteinuria (P < 0.001) and low serum albumin (P
      < 0.00001). In 154 patients who were studied further, subnormal factor X activity
      (FX:C) was found in 22 cases (14%). In cases with subnormal FX:C, the
      corresponding factor X antigen (FX:Ag) measurements were consistently higher
      (median FX:Ag/FX:C 2.5, range 0.81-9.25, n = 16) than cases with normal FX:C
      (median FX:Ag/FX:C 0.96, range 0.65-1.29, n = 28, P < 0.0001). No evidence was
      found of an FX inhibitor. Of the 48/154 (31%) cases with a prolonged TT, the
      reptilase time was also prolonged in 38/48 cases (79%). These data show that
      haemorrhage and abnormal coagulation are common in AL-amyloidosis and are
      multifactorial in origin. We provide evidence suggesting that hepatic amyloid
      infiltration and nephrotic syndrome are determinants of the TT. In most patients,
      prolongation of the PT was explained by reduction in FX:C, but this was not
      wholly explained by a reduction in FX:Ag.

PMID- 10971409
TI  - Central venous access devices in children with congenital coagulation disorders:
      complications and long-term outcome.
AB  - Reliable venous access is essential to facilitate the administration of
      prophylactic factor concentrate or blood products in children with congenital
      coagulation disorders and immune tolerance therapy (ITT) regimens in those who
      develop high responding inhibitors. Poor venous access is even more problematic
      in very young children, the vast majority of whom will require the insertion of
      central venous access devices (CVADs). Previous studies have suggested that
      infection rates are low and that there are few long-term complications associated
      with CVAD usage. We have reviewed 86 CVADs that have been inserted, since 1988,
      in 58 children with congenital bleeding disorders, aged 6 d to 16.5 years,
      attending Great Ormond Street Hospital, London, and the National Children's
      Hospital, Dublin. The devices have remained in situ for 2 weeks to 92 months
      (median 22.5 months). Early (0-2 weeks) complications of CVAD insertion included
      nine bleeding episodes, one extravasation of factor concentrate, three allergic
      reactions to factor concentrate and five catheter infections. Overall, CVAD
      infection was the commonest problem encountered, with 52 devices (60%) becoming
      infected. Twenty-seven CVADs (31%) required removal. Infection rates in children
      without inhibitors (29/68) were 1/20 patient-months or 1. 6 infections/1000
      patient-days, but infection rates for those with inhibitors were 1/8.5 patient
      months or 4.3/1000 patient-days. Staphylococcus epidermidis was the predominant
      organism (25/52) isolated. Blockage of CVAD (four) and catheter disconnection
      (four) were the most frequently occurring non-infectious long-term complications.
      Skin erosion of the port was also seen in three children, in one child at 20
      months, in one at 29 months and in one at 34 months after insertion. This study
      demonstrates a high CVAD infection rate and highlights the long-term
      complications of CVAD usage.

PMID- 10971410
TI  - The 4G/4G genotype at nucleotide position -675 in the promotor region of the
      plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients
      with minor stroke than in controls.
AB  - Genetic risk factors play an important role in the aetiology of vascular
      diseases. The insertion/deletion polymorphism (4G/5G) in the promotor region of
      the plasminogen activator inhibitor 1 (PAI-1) gene has been associated with an
      increased risk of myocardial infarction. We investigated 136 patients with minor
      stroke (MS) and transient ischaemic attack (TIA) and found a prevalence of 0.32
      for the 4G/4G genotype in patients compared with 0.42 in 115 age-matched healthy
      controls. The 4G/4G genotype was significantly less frequent among 61 patients
      symptomatic before the age of 60 years (prevalence 0.20) than in 75 patients
      symptomatic after 60 years of age (prevalence 0.42; odds ratio). Our results
      indicate that the 4G/4G genotype is not a risk factor for MS or TIA and may even
      be protective in young patients.

PMID- 10971411
TI  - Different levels of prion protein (PrPc) expression on hamster, mouse and human
      blood cells.
AB  - The host prion protein, PrPc, and its conformationally changed isoform, PrPsc,
      play an essential role in the transmissible spongiform encephalopathy (TSE)
      infections. The prion hypothesis postulates that PrPsc is the TSE infectious
      agent and that it serves as a template to convert host PrPc to additional PrPsc.
      Blood of experimentally TSE-infected rodents has been shown to contain TSE
      infectivity. If blood-borne TSE infectivity requires association with PrPc,
      differences in the distribution of PrPc in blood could affect the amount and
      distribution of blood-borne infectivity in different hosts. We have compared the
      distribution of PrPc on the peripheral blood cells of humans, hamsters and mice
      using quantitative flow cytometry. Human lymphocytes, monocytes and platelets
      displayed much greater quantities of PrPc than corresponding mouse cells. Mouse
      platelets did not express any detectable PrPc. A similar low level of PrPc was
      found on both human and mouse red blood cells. None of the hamster peripheral
      blood cells displayed detectable amounts of PrPc. If PrPc contributes to the
      propagation or transport of TSE infectivity in blood, the species differences in
      PrPc distribution reported here need to be considered when extrapolating the
      results of rodent TSE transmission studies with blood and blood components to
      humans.

PMID- 10971412
TI  - Monoclonal antibody-mediated inhibition of the human HLA alloimmune response to
      platelet transfusion is antigen specific and independent of Fcgamma receptor
      mediated immune suppression.
AB  - Presensitization of donor platelets with allo-specific immunoglobulin (Ig)G
      results in a diminished immune response against subsequent transfusions of
      platelets. To understand better the mechanism of how alloantibody
      presensitization results in a decreased alloimmune response, we have used murine
      monoclonal antibodies directed to polymorphic and non-polymorphic regions of
      human leucocyte antigen (HLA) as well as platelet-specific molecules. Here, we
      demonstrated that presensitization with anti-human HLA class I antibodies, as
      well as beta2-microglobulin-specific antibody, protected against alloantibody
      production to five subsequent untreated platelet challenges. Use of complement
      fixing, non-fixing or F(ab')2 fragments of HLA-specific antibody also resulted in
      complete inhibition of alloantibody production. This protection was not seen when
      the platelets were presensitized with monoclonal antibodies to CD42a (GPIX), CD32
      (low-affinity IgG/Fcgamma receptor) or murine IgG and was thus independent of B
      cell FcgammaRII-mediated immune suppression. The inhibition observed was
      independent of HLA alloantigenic specificity as antibodies directed at the beta2
      microglobulin portion of HLA class I were as effective as antibodies against any
      of the HLA-alpha regions (either polymorphic or non-polymorphic) of class I. This
      work demonstrates that monoclonal antibody-mediated suppression of the human HLA
      alloimmune response to platelet transfusion is antigen specific and is
      independent of FcgammaRII-mediated immune regulation, complement fixing or HLA
      alloantigenic specificity.

PMID- 10971413
TI  - Withdrawal of enzyme replacement therapy in Gaucher's disease.
AB  - Although enzyme replacement therapy is safe and effective in ameliorating the
      signs and symptoms of Gaucher's disease, some patients have withdrawn from
      treatment. The purpose of this study was to evaluate the response to withdrawal
      and to discuss the implications for patients currently on unaltered therapy
      regimens since the advent of treatment. Fifteen patients, who had been treated
      with enzyme replacement for 5-56 months and then withdrew for 8-47 months, were
      assessed for changes in haematological parameters and in liver and spleen index
      volume. Despite non-uniformity of duration of on and off periods, degree of
      organomegaly, anaemia and thrombocytopenia, most patients did not revert to
      respective baseline values in most parameters after withdrawal. None of the
      patients suffered exacerbation of bone involvement or had new or aggravated
      pulmonary hypertension. Adult patients with stable Gaucher's disease may be
      withdrawn from therapy for circumscribed periods without forfeiting most gains
      accrued during enzyme therapy. Therefore, stopping and restarting may be
      considered in some patients. Alternatively, maintenance at reduced dosage and/or
      frequency may be appropriate in some adult patients who are stable or non
      responsive after the first years of enzyme therapy. This caveat does not apply to
      children.

PMID- 10971414
TI  - Enteral versus parenteral nutrition.

PMID- 10971415
TI  - SURGICAL PUBLISHING: what an editor wants or expects from authors

PMID- 10971416
TI  - Committee on publication ethics

PMID- 10971417
TI  - Abdominal fluid collection after laparoscopic cholecystectomy.

PMID- 10971418
TI  - Lymphoedema following surgery for breast cancer.
AB  - BACKGROUND: Lymphoedema is a common complication of breast cancer treatment,
      affecting approximately a quarter of patients. Those affected can have an
      uncomfortable, unsightly and sometimes functionally impaired limb prone to
      episodes of superficial infection. The aetiology, pathophysiology and management
      of these patients is poorly understood. METHODS: This is a systematic review of
      all published literature on lymphoedema following treatment for breast cancer,
      using the Medline and Cinahl databases with cross-referencing of major articles
      on the subject up to the end of 1999. RESULTS AND CONCLUSION: The aetiology and
      pathophysiology of lymphoedema in patients with breast cancer appear to be
      multifactorial and are still not fully understood. Although conservative
      treatment techniques can be very successful in controlling symptoms, they do not
      afford a cure. The place of surgical and pharmacological therapy remains unclear.
      Improved understanding of the pathophysiology may assist in reducing the
      incidence of this condition, or help to identify those at greatest risk, in whom
      early initiation of conservative treatment measures may prove effective.

PMID- 10971419
TI  - Surgery for colorectal liver metastases with hepatic lymph node involvement: a
      systematic review.
AB  - BACKGROUND: Liver resection for colorectal metastases is the only known treatment
      associated with long-term survival; extrahepatic disease is usually considered a
      contraindication to such treatment. However, some surgeons do not regard spread
      to the hepatic lymph nodes as a contraindication provided that these nodes can be
      excised adequately. A systematic review of the literature was undertaken to
      address this issue. METHODS: An electronic search using Medline, Cancerlit and
      Embase databases was performed for studies reporting liver resection for
      colorectal metastases from 1964 to 1999. Data were extracted from papers
      reporting outcome for patients with positive hepatic nodes and analysed according
      to predetermined criteria. RESULTS: Fifteen studies were identified that gave
      survival data on 145 node-positive patients. Five patients were reported to have
      survived 5 years after liver resection; one was disease free, two had recurrent
      disease and the disease status was not described in the remaining two. Five
      studies containing 83 patients specified a formal lymph node dissection as part
      of the surgical procedure and four of the five node-positive 5-year survivors
      were from these studies. CONCLUSION: There are few 5-year survivors after liver
      resection, with or without lymph node dissection, for colorectal hepatic
      metastases involving the hepatic lymph nodes.

PMID- 10971420
TI  - DIGEST: digest
AB  - Professor Seiki Matsuno, Chief Editor oy Surgery Today (The Japanese Journal of
      Surgery), has selected from the January to March 2000 issues of the journal for
      this quarter's digest. A digest of BJS for the same period written by Professor
      Pierre Guillou, Associate Editor, appears in the Japanese journal.

PMID- 10971421
TI  - Prospective randomized trial of low-pressure pneumoperitoneum for reduction of
      shoulder-tip pain following laparoscopy.
AB  - BACKGROUND: Postoperative shoulder-tip pain occurs frequently following
      laparoscopic cholecystectomy. The aim of this randomized clinical trial was to
      evaluate the efficacy of a low-pressure carbon dioxide pneumoperitoneum during
      laparoscopic surgery in reducing the incidence of postoperative shoulder-tip
      pain. METHODS: Ninety consecutive patients undergoing laparoscopic
      cholecystectomy were randomized prospectively into low-pressure (group A) and
      normal-pressure (group B) laparoscopic cholecystectomy groups. Patients in group
      A (n = 46) underwent laparoscopic cholecystectomy with 9 mmHg carbon dioxide
      pneumoperitoneum during most of the operation, and those in group B (n = 44) had
      laparoscopic cholecystectomy with 13 mmHg pneumoperitoneum. Shoulder-tip pain was
      recorded on a visual analogue pain scale 1, 3, 6, 12, 24 and 48 h after
      operation. RESULTS: The low-pressure pneumoperitoneum did not increase the
      duration of surgery. There were no significant intraoperative or postoperative
      complications in either group. Fourteen patients (32 per cent) in group B and
      five (11 per cent) in group A complained of shoulder pain (P<0.05). Mean shoulder
      tip pain scores at 12 and 24 h and postoperative analgesia requirements were also
      significantly lower in the low-pressure laparoscopic cholecystectomy group
      (P<0.001). CONCLUSION: A carbon dioxide pneumoperitoneum pressure lower than that
      usually utilized to perform laparoscopic surgery reduces both the frequency and
      intensity of shoulder-tip pain following laparoscopic cholecystectomy.

PMID- 10971422
TI  - Pilot randomized controlled study of preservation or division of ilioinguinal
      nerve in open mesh repair of inguinal hernia.
AB  - BACKGROUND: There is uncertainty as to whether preservation or elective division
      of the ilioinguinal nerve influences pain and sensory loss following inguinal
      hernia repair. METHODS: In 20 men with primary bilateral inguinal hernias
      undergoing open tension-free mesh repair, the sides (right or left) were
      randomized for preservation or division of the ilioinguinal nerve. Patients were
      reviewed on day 1, 4 weeks and 6 months after operation. Any pain or numbness, as
      well as any loss of sensation in the area supplied by the nerve, was recorded.
      RESULTS: No significant difference was seen in pain or numbness between the
      divided and preserved sides. Sensory loss detected by clinical examination was
      more common following the division of the nerve compared with preservation.
      CONCLUSION: Within the limitations of a small sample size, elective division of
      the ilioinguinal nerve during inguinal hernia repair does not appear to be
      associated with a significant increase in postoperative symptoms.

PMID- 10971424
TI  - Prospective analysis of a scoring system to predict choledocholithiasis.
AB  - BACKGROUND: The management of choledocholithiasis in the laparoscopic era remains
      debatable. A common policy is to perform preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) on patients suspected of having common bile duct
      (CBD) stones, using standard risk criteria. The aim of this study was to evaluate
      prospectively a scoring system designed to improve the accuracy of CBD stone
      prediction before laparoscopic cholecystectomy. METHODS: Known clinical,
      biochemical and radiological risk factors for CBD stones were analysed
      retrospectively in 233 patients. The presence (n = 77) or absence (n = 156) of
      CBD stones was determined by preoperative ERCP and/or laparoscopic
      cholangiography. Using multivariate analysis, the significant risk factors for
      CBD stones were identified and a new preoperative scoring system was developed. A
      score of 3 or more was taken as the cut-off point to suggest CBD stones and the
      need for preoperative ERCP. This scoring system was then tested prospectively in
      211 consecutive patients with symptomatic gallstones requiring surgery. Patients
      whose bile ducts could not be demonstrated by ERCP or operative cholangiography
      were excluded. RESULTS: Fifty-five patients scored 3 or more (predicted ERCP rate
      of 29 per cent), of whom 23 (42 per cent) had proven CBD stones. Intraoperative
      cholangiography was successful in 87 per cent. Five patients (4 per cent) who
      scored less than 3 had small stones (less than 5 mm) demonstrated at operative
      cholangiography. The overall sensitivity and specificity of this scoring were 82
      and 80 per cent respectively. CONCLUSION: Formal risk assessment of the presence
      of CBD stones using this scoring system is simple and may be used for
      preoperative selection of patients for biliary tract imaging by magnetic
      resonance cholangiography or ERCP.

PMID- 10971423
TI  - Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock
      proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous
      administration of doxorubicin.
AB  - BACKGROUND: Pharmacological preconditioning may induce a stress response which
      protects liver against ischaemia-reperfusion injury (IRI). The aim of this study
      was to determine, in an animal model, whether intravenous administration of
      doxorubicin induces heat shock proteins (HSPs) in liver tissue and facilitates
      liver tolerance to subsequent warm IRI. METHODS: Male Wistar rats were used.
      Production of HSPs was determined in liver tissue sequentially after the
      injection of doxorubicin 1 mg/kg body-weight. Acquisition of tolerance for 30 min
      warm ischaemia and reperfusion of the liver was determined in animals pretreated
      (48 h beforehand) with doxorubicin, and in controls. Biochemical liver function
      and liver adenine nucleotide concentration 40 min after reperfusion and survival
      rate at 7 days after the ischaemic insult were recorded. RESULTS: Expression of
      HSP72 and HSP73 in the liver was confirmed 48 h after doxorubicin administration.
      Biochemical parameters and survival rates were significantly better in pretreated
      animals than in controls. CONCLUSION: These results indicate that doxorubicin has
      the potential to provide the liver with tolerance against IRI. A simultaneous
      increase of both HSP72 and HSP73 in liver tissue may explain the acquisition of
      tolerance following the administration of doxorubicin.

PMID- 10971425
TI  - Retrospective analysis of prognostic factors after liver resection and
      transplantation for cholangiocellular carcinoma.
AB  - BACKGROUND: Cholangiocellular carcinoma is an uncommon primary liver cancer,
      which may be mixed with hepatocellular carcinoma. A retrospective analysis was
      undertaken to evaluate the results of surgical treatment and to identify
      prognostic factors. METHODS: Between 1978 and 1996, 162 patients underwent
      surgery for cholangiocellular carcinoma: liver resection (n = 95), liver
      transplantation (n = 24) and exploratory laparotomy with and without drainage (n
      = 43). Univariate and multivariate analyses of prognostic factors were performed.
      RESULTS: Overall survival was 47 per cent at 1 year, 28 per cent at 2 years and
      13 per cent at 5 years. Survival rates for patients with resectable tumours were
      64, 43 and 21 per cent respectively, and for those who underwent liver
      transplantation 21, 8 per cent and zero respectively. Univariate analysis showed
      that the following variables had an effect on survival: age, jaundice, liver
      resection, T, N and M stage in the tumour node metastasis classification, Union
      Internacional Contra la Cancrum (UICC) tumour stage, tumour-free margins,
      vascular infiltration, tumour number, tumour size and serum level of
      carcinoembryonic antigen. Multivariate analysis identified jaundice, N and M
      category, and UICC tumour stage as independent prognostic factors. CONCLUSION:
      The data underscore the importance and prognostic value of the UICC tumour
      classification for cholangiocellular carcinoma. The prognosis of mixed tumours is
      no different. Liver resection remains the treatment of choice; transplantation
      offers no solution for otherwise unresectable tumours.

PMID- 10971426
TI  - Molecular changes in extracellular matrix turnover after renal ischaemia
      reperfusion injury.
AB  - BACKGROUND: Renal ischaemia-reperfusion (IR) injury is an inevitable consequence
      of transplantation and contributes to later graft fibrosis. This study aimed to
      elucidate the possible mechanisms by studying the expression of genes associated
      with extracellular matrix (ECM) turnover. METHODS: Male Wistar rats underwent
      laparotomy, clamping of the right renal pedicle for 45 min, and left nephrectomy.
      Control animals underwent left nephrectomy only, or had no operation. Animals
      were killed at 8, 16 and 24 weeks and messenger RNA was extracted from renal
      tissue. Genes of interest were amplified and then quantified in an enzyme-linked
      immunosorbent assay system with levels expressed as a ratio to a known
      housekeeping gene (GAPDH). RESULTS: Experimental animals developed progressive
      proteinuria from 16 weeks onwards. At 8 weeks after IR injury, gene levels of
      matrix metalloproteinase (MMP) 2, an ECM-degrading enzyme, were significantly
      increased. Levels then fell progressively. This was associated with increasing
      expression of tissue inhibitor of metalloproteinases (TIMP) 1, an inhibitor of
      MMP-2, and of transforming growth factor (TGF) beta, a profibrotic cytokine, by
      24 weeks following injury. CONCLUSION: These results suggest that, after an
      initial phase of increased ECM turnover following IR injury, the balance turns
      towards one of reduced degradation. This is likely to be an important mechanism
      in the subsequent development of fibrosis.

PMID- 10971427
TI  - Effect of colectomy on gastric emptying in idiopathic slow-transit constipation.
AB  - INTRODUCTION: Gastric emptying is delayed in patients with idiopathic slow
      transit constipation (ISTC). Gastric emptying was measured before and after
      colectomy and ileorectal anastomosis in patients with ISTC to determine whether
      the abnormality persists after operation. METHODS: Twelve patients undergoing
      colectomy for severe ISTC had solid-phase gastric emptying measured after an
      overnight fast. All 12 had an uncomplicated subtotal colectomy and ileorectal
      anastomosis; 11 had an excellent functional outcome. In ten of these patients
      gastric emptying was repeated within 3 months of operation. Seven patients
      (including the remaining two) had the study performed at 1 year. RESULTS: All 12
      patients had severely delayed gastric emptying before operation. Gastric emptying
      remained delayed in the ten patients who underwent an early postoperative gastric
      emptying study. Six of seven patients assessed at 1 year had improved gastric
      emptying, of whom four had returned to normal. Functional outcome did not relate
      to gastric emptying. CONCLUSION: Patients with ISTC have delayed gastric
      emptying. In some patients this returns to normal after colectomy, but is
      persistent in others. This may have implications for our understanding of ISTC.

PMID- 10971428
TI  - Prognostic significance of extensive microsatellite instability in sporadic
      clinicopathological stage C colorectal cancer.
AB  - BACKGROUND: Colorectal cancers exhibiting microsatellite instability (MSI) appear
      to have unique biological behaviour. This study analyses the association between
      extensive MSI (MSI-H), clinicopathological features and survival in an unselected
      group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C
      (tumour node metastasis stage III) colorectal cancer. METHODS: Some 255 patients
      who underwent resection for sporadic ACPS C colorectal cancer between 1986 and
      1992 were studied. No patient had received chemotherapy. Minimum follow-up for
      all patients was 5 years. Archival normal and tumour DNA was extracted and
      amplified by polymerase chain reaction using a radioactive labelling technique.
      MSI-H was defined as instability in 40 per cent or more of seven markers.
      RESULTS: Twenty-one patients showed MSI-H. No association was found between MSI
      and age or sex. Tumours exhibiting MSI-H were more commonly right sided
      (P<0.00001), larger (P = 0.002) and more likely to be high grade (P = 0.049).
      After adjustment for age, sex and other pathological variables, patients whose
      cancers exhibited MSI-H had improved survival (P = 0.015). CONCLUSION:
      Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers
      with improved prognosis. Such stratification should be considered in trials of
      adjuvant therapy and may be relevant to therapeutic decision making.

PMID- 10971429
TI  - Vertical reduction rectoplasty: a new treatment for idiopathic megarectum.
AB  - BACKGROUND: The aetiology of idiopathic megarectum is unknown and the results of
      surgery are often unsatisfactory. Rectal hyposensation is common and poor
      perception of rectal filling may contribute to the poor evacuatory function. By
      reducing the capacity of the rectum, it was hypothesized that sensory thresholds
      to rectal distension and perception of urge to defaecate would be improved.
      METHODS: Vertical reduction rectoplasty (VRR) and concomitant sigmoid colectomy
      was performed on six patients with idiopathic megarectum. Patients were evaluated
      before and after operation by detailed questionnaire and anorectal physiology.
      Postoperative rectal compliance was also studied by means of a programmable
      electronic barostat. Where appropriate, physiological data were compared with
      those obtained in eight healthy volunteers. RESULTS: Bowel frequency increased
      from a preoperative median of 2.5 to 16 per month after operation. Four patients
      reported improved rectal perception of the urge to defaecate. Thresholds for
      defaecatory urge and maximum tolerated volume were significantly reduced
      following VRR (P<0.05). Post-VRR rectal compliance was no different from that in
      healthy volunteers. Colonic transit time decreased significantly after VRR
      (P<0.05) and evacuation on proctography increased from a median of 30 per cent to
      50 per cent. At a median of 57 weeks' follow-up five of the six patients
      expressed continued satisfaction with the results. CONCLUSION: VRR is a new
      approach to the treatment of idiopathic megarectum. Clinical and physiological
      studies confirm that it can improve sensory feedback and defaecation. The
      procedure needs further evaluation as the number of patients undergoing the
      procedure increases.

PMID- 10971430
TI  - Anal vector volume analysis complements endoanal ultrasonographic assessment of
      postpartum anal sphincter injury.
AB  - BACKGROUND: The aim of this study was to determine the role of anal vector
      manometry in the assessment of postpartum anal sphincter injury and to establish
      the most suitable method of anal vector volume analysis for identifying
      significant external anal sphincter (EAS) injury in an at-risk parous population.
      METHODS: A total of 101 consecutive women with a history of instrumental or
      traumatic vaginal delivery was recruited. Anal ultrasonography and anal vector
      manometry were performed. Receiver-operator characteristic curves were used to
      determine the usefulness of anal manometry and anal vector volume analysis in the
      identification of significant EAS disruption (full thickness, more than one
      quadrant involved) detected by ultrasonography. RESULTS: Seventeen women had
      significant EAS disruption identified by anal ultrasonography. Anal vector
      manometry provided complementary functional information. Anal vector symmetry
      index (VSI), determined by analysis of mean maximum squeeze pressure, yielded 100
      per cent sensitivity for significant EAS disruption, with a positive predictive
      value of 61 per cent. CONCLUSION: Anal vector manometry complements endoanal
      ultrasonography. VSI, determined by means of the squeeze pressure profile,
      correlates best with significant EAS disruption identified at anal
      ultrasonography.

PMID- 10971431
TI  - Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)
      are important in tumour invasion and metastasis. The levels of MMPs, TIMPs and
      total MMP activity were compared in paired colorectal tumour (n = 50) and normal
      tissue (n = 49) samples and correlated with clinical and pathological staging.
      METHODS: Gelatin zymography (MMP-2 and MMP-9), enzyme-linked immunosorbent assays
      (MMP-1, MMP-3, TIMP-1 and TIMP-2) and quenched fluorescent substrate hydrolysis
      (total MMP activity) were employed in resection specimens from 50 patients, four
      with adenomas and 46 with colorectal cancer. RESULTS: The levels of active MMP-2
      and MMP-9 and total MMP-1, MMP-3 and TIMP-1 were significantly greater in tumour
      tissue than in normal colon (e.g. TIMP-1 tumour median 72 (range 25-351) versus
      normal 26 (4-107) ng per mg total protein content; P<0.05); however, TIMP-2
      levels were significantly greater in normal tissue (P<0.05). Total MMP activity
      was significantly greater in tumour than in normal tissue (15 025 (1750-174 400)
      versus 7250 (750-354 650) pmol l-1 min-1 mg protein-1; P<0.05). Correlations were
      found between both MMP and TIMP levels and pathological tumour staging. MMP-1
      appeared to be most important as its concentration correlated positively with
      Dukes staging, tumour differentiation and lymphatic invasion. CONCLUSION: The
      levels of the studied MMPs and total MMP activity were upregulated in colorectal
      tumours. MMP-1 is important in colorectal cancer progression.

PMID- 10971432
TI  - Hyaluronic acid-based agents do not affect anastomotic strength in the rat colon,
      in either the presence or absence of bacterial peritonitis.
AB  - BACKGROUND: Hyaluronic acid (HA) agents reduce postsurgical adhesion formation.
      The effect of their perioperative administration on early anastomotic healing is
      unknown. This study investigated the influence of two HA-containing agents on the
      development of strength in colonic anastomosis during the first postoperative
      week, both in normal rats and in rats with bacterial peritonitis. METHODS: In 90
      male Wistar rats a 1-cm segment was resected from the descending colon and an end
      to-end anastomosis was constructed. In 108 rats a bacterial peritonitis was
      induced using caecal ligation and puncture (CLP). Some 24 h after CLP the abdomen
      was reopened, the caecum was taken out and, after resection of a 1-cm segment, an
      anastomosis was made. Animals in both groups were randomized to receive either an
      HA-carboxymethylcellulose (CMC) bioresorbable membrane, 0.4 per cent HA solution
      or no treatment. One-third of each group was killed at day 1, 3 and 7 after
      operation. Cultures were taken from the abdominal cavity for microbiological
      analysis in half of the animals. Subsequently, both bursting pressure and
      breaking strength were determined as parameters for anastomotic strength.
      RESULTS: No differences in anastomotic bursting pressure or breaking strength
      were found between the experimental groups and their controls. In addition, there
      was no significant difference in the number of bacteria cultured from the
      abdominal cavity between rats treated with HA and controls. CONCLUSION: Neither
      HA-CMC bioresorbable membrane nor 0.4 per cent HA solution interferes with the
      development of early anastomotic strength in the colon, and can therefore be
      safely used to prevent intra-abdominal adhesion formation after performing bowel
      anastomosis.

PMID- 10971433
TI  - Diagnosis and treatment of portal vein thrombosis following splenectomy.
AB  - BACKGROUND: Portal vein thrombosis is a rare but potentially fatal complication
      of splenectomy. The aim of this study was to assess the incidence, risk factors,
      treatment and outcome of portal vein thrombosis after splenectomy in a large
      series of patients. METHODS: All patients who had undergone a splenectomy in the
      University Hospital, Rotterdam, between 1984 and 1997 were reviewed
      retrospectively. Splenectomy that was followed by symptomatic portal vein
      thrombosis was selected for analysis. Risk factors for portal vein thrombosis
      were sought. RESULTS: Of 563 splenectomies, nine (2 per cent) were complicated by
      symptomatic portal vein thrombosis. All these patients had either fever or
      abdominal pain. Two of 16 patients with a myeloproliferative disorder developed
      portal vein thrombosis after splenectomy (P = 0.03), and four of 49 patients with
      haemolytic anaemia (P = 0.005). Treatment within 10 days after splenectomy was
      successful in all patients, while delayed treatment was ineffective. CONCLUSION:
      Portal vein thrombosis should be suspected in a patient with fever or abdominal
      pain after splenectomy. Patients with a myeloproliferative disorder or haemolytic
      anaemia are at higher risk; they might benefit from early detection and could
      have routine Doppler ultrasonography after splenectomy.

PMID- 10971434
TI  - Estimation of lymph node metastasis by size in patients with intrathoracic
      oesophageal cancer.
AB  - BACKGROUND: The preoperative evaluation of lymphatic metastasis in patients with
      oesophageal cancer is of vital importance in determining a therapeutic strategy.
      The aim of this study was to establish criteria for the preoperative diagnosis of
      lymph node metastases based on the size and shape of nodes. METHODS: Some 123
      patients with intrathoracic oesophageal cancer were studied and 6822 nodes were
      obtained by extended lymphadenectomy. The nodes were classified anatomically and
      their size was measured by the operating surgeon during or immediately after
      operation. All were examined histologically and criteria for the diagnosis of
      metastasis were evaluated. RESULTS: The size of the lymph nodes varied by
      anatomical site. Nodes were smallest in the neck and largest at the tracheal
      bifurcation. The cut-off value for the diagnosis of metastasis was 5 mm in the
      neck, 6 mm in the abdomen and 8 mm in the mediastinum, except for tracheal nodes.
      Lymph nodes 10 mm or larger tended to become spherical when involved by
      metastasis. CONCLUSION: The incidence of metastasis in each lymph node can be
      estimated by its size. Discounting nodes less than 10 mm can lead to an
      underestimation of the stage of oesophageal cancer during preoperative
      evaluation.

PMID- 10971435
TI  - Natural history of patients with adhesive small bowel obstruction.
AB  - BACKGROUND: Small bowel obstruction (SBO) is a major cause of morbidity and
      financial expenditure. The goals of this study were to determine factors
      predisposing to adhesive SBO, to note the long-term prognosis and recurrence
      rates for operative and non-operative treatment, to elicit the complication rate
      of operations and to highlight factors predictive of recurrence. METHODS: The
      medical records of all patients admitted to one hospital between 1986 and 1996
      with the diagnosis of SBO were reviewed retrospectively. This included 410
      patients accounting for 675 admissions. RESULTS: The frequency of previous
      operation by procedure type was colorectal surgery (24 per cent), followed by
      gynaecological surgery (22 per cent), herniorrhaphy (15 per cent) and
      appendicectomy (14 per cent). A history of colorectal surgery (odds 2.7) and
      vertical incisions (odds 2.5) tended to predispose to multiple matted adhesions
      rather than an obstructive band. At initial admission 36 per cent of patients
      were treated by means of operation. As the number of admissions increased, the
      recurrence rate increased while the time interval between admissions decreased.
      Patients with an adhesive band had a 25 per cent readmission rate, compared with
      a 49 per cent rate for patients with matted adhesions (P<0.004). At the initial
      admission 36 per cent of patients were treated surgically. Patients treated
      without operation had a 34 per cent readmission rate, compared with 32 per cent
      for those treated surgically (P not significant), a shorter time to readmission
      (median 0.7 versus 2.0 years; P<0.05), no difference in reoperation rate (14
      versus 11 per cent; P not significant) and fewer inpatient days over all
      admissions (4 versus 12 days; P<0.0001). CONCLUSION: The likelihood of
      reobstruction increases and the time to reobstruction decreases with increasing
      number of previous episodes of obstruction. Patients with matted adhesions have a
      greater recurrence rate than those with band adhesions. Non-operative treatment
      for adhesions in stable patients results in a shorter hospital stay and similar
      recurrence and reoperation rates, but a reduced interval to reobstruction when
      compared with operative treatment.

PMID- 10971436
TI  - Changes in pancreatic resection for chronic pancreatitis over 28 years in a
      single institution.

PMID- 10971437
TI  - Some personal thoughts on plagiarism.

PMID- 10971438
TI  - Changing patterns in the management of gastric volvulus over 14 years.

PMID- 10971439
TI  - Prognostic significance of oestrogen receptor beta in breast cancer.

PMID- 10971440
TI  - Pain after laparoscopic cholecystectomy.

PMID- 10971441
TI  - CORRESPONDENCE: Authors' reply

PMID- 10971442
TI  - Thyroid disease in relation to pregnancy: a decade of change.
AB  - Inspection of the references cited in this review indicates that much work has
      occurred in the area of thyroid and pregnancy during the last decade. Significant
      advances in our understanding of the immunology of pregnancy and the effect of
      thyroid disease on this process have taken place. The role of hCG in the
      physiology of pregnancy and its relevance to thyroid function has been an
      emerging theme. There is still no clear explanation for the association between
      thyroid antibodies and infertility or miscarriage. During the last decade a
      general concensus has developed in relation to the management of hyperthyroidism
      in pregnancy although there are still variations in antithyroid drug use at this
      time. The aetiological classification of congenital hyper- and hypothyroidism
      utilizing new technologies has opened up a new perspective on these disorders.
      Attention has been drawn to the importance of treating maternal hypothyroidism
      with adequate thyroid replacement therapy and to the possibility of impaired
      child neuropsychological development consequent on low maternal thyroid hormone
      concentration in early gestation in non iodine deficient areas. Significant
      advances have been made during the last decade in the description of the clinical
      features and in our understanding of the pathogenesis of postpartum thyroid
      disease. The importance of long-term follow up of selected patient groups has
      also been emphasized.

PMID- 10971443
TI  - GH deficiency in the elderly: the case for GH replacement.

PMID- 10971444
TI  - Growth hormone deficiency and replacement in elderly hypopituitary adults. KIMS
      Study Group and the KIMS International Board. Pharmacia and Upjohn International
      Metabolic Database.
AB  - OBJECTIVE: Although elderly hypopituitary adults demonstrate an increase in total
      and central fat compared with age-matched controls and are distinguishable from
      control subjects in terms of growth hormone (GH) responsiveness on dynamic
      testing, there are few data available on response to GH replacement. The
      objective of this study was to compare the baseline characteristics and
      longitudinal response to GH replacement in patients aged > 65 years with that
      observed in younger patients enrolled in KIMS (Pharmacia and Upjohn International
      Metabolic Database). KIMS is a physician-managed, open, long-term surveillance
      study of adult GH-deficient patients receiving GH replacement. Patients were
      entered and data provided by interested physicians. PATIENTS: Baseline
      characteristics were studied in 109 patients (66 males) aged > 65 years
      commencing GH replacement at time of entry into KIMS and the effects of GH
      replacement on blood pressure, lipids and quality of life in 64 patients who had
      completed at least 6 months of GH replacement. Data were compared with baseline
      data on 863 patients aged < 65 years with adult onset GH deficiency, who had not
      received GH for at least 6 months prior to entry into KIMS, 220 of whom went on
      to complete > 6 months GH therapy in KIMS. RESULTS: Blood pressure, cholesterol
      and LDL cholesterol were positively correlated with age, particularly in females,
      and older patients had a predictably higher prevalence of diabetes mellitus and
      history of hypertension. The frequency of previous fractures was increased in
      females but not in males aged > 65 years. Body mass index, waist/hip ratio and
      quality of life (AGHDA score) was similar in both groups prior to commencement of
      GH therapy. GH replacement doses were similar in younger and older patients and
      the percentage of patients with serum IGF-I of > 2SD above the age-related normal
      mean was not significantly different between the groups (< 65 years, 20%; > 65
      years, 11%). After 6 months of GH replacement significant improvements were
      evident in waist circumference, waist/hip ratio, diastolic blood pressure, total
      and LDL cholesterol and AGHDA score in patients aged < 65 years. Similar
      significant reductions in total and LDL cholesterol were evident in patients > 65
      years. In addition, male patients aged > 65 years demonstrated significant
      reductions in diastolic blood pressure and AGHDA score but no change in waist
      circumference whereas females aged > 65 years demonstrated a trend to reduction
      in waist circumference and AGHDA score. CONCLUSIONS: These data, derived from the
      largest series of GH-treated hypopituitary patients published to date, confirm
      similar baseline characteristics and positive benefit from GH replacement in
      older compared with younger hypopituitary patients particularly in relation to
      quality of life.

PMID- 10971445
TI  - Autoantibodies to the flavoprotein subunit of succinate dehydrogenase: analysis
      of specificity in autoimmune thyroid disease.
AB  - OBJECTIVE: Thyroid-associated ophthalmopathy is a progressive eye disorder
      affecting the extraocular muscle and orbital connective tissue and is considered
      to have an autoimmune aetiology. A recent study reported a close relationship
      between serum antibodies against the flavoprotein subunit of succinate
      dehyhdrogenase (SDHFp) and active thyroid-associated ophthalmopathy involving eye
      muscle damage. The aim of the present study was to develop a sensitive and
      quantitative radiobinding assay for the detection of antibodies to the
      flavoprotein subunit of succinate dehydrogenase and to use this to determine the
      distribution of antibodies in different patient groups. DESIGN AND PATIENTS:
      Serum samples from the following patient groups were analysed: 20 systemic lupus
      erythematosus; 20 Addison's disease; 26 autoimmune hypothyroidism; 28 Graves'
      hyperthyroidism; 12 pretibial myxoedema; 25 thyroid-associated ophthalmopathy.
      Sera from 20 healthy subjects were used as controls. [35S]-labelled succinate
      dehydrogenase flavoprotein was produced in an in vitro transcription-translation
      system and subsequently used in immunoprecipitation experiments with sera from
      patient and control groups to test for the presence of antibodies to the
      flavoprotein. RESULTS: Succinate dehydrogenase flavoprotein antibodies were
      detected in five of the 20 (25%) patients with Addison's disease, six of the 20
      (30%) with systemic lupus erythematosus, five of the 26 (19%) with autoimmune
      hypothyroidsm, six of the 28 (21%) with Graves' hyperthyroidism, two of the 12
      (17%) with pretibial myxoedema and three of the 25 (12%) with thyroid-associated
      ophthalmopathy. The frequencies of flavoprotein antibodies were significantly
      greater than controls (P-value < 0.05) for patients with systemic lupus
      erythematosus (P = 0.02), but not for patients with either Addison's disease (P =
      0.05), pretibial myxoedema (P = 0.13), Graves' hyperthyroidism (P = 0.07),
      autoimmune hypothyroidism (P = 0.06) or thyroid-associated ophthalmopathy (P =
      0.24). For the patients with thyroid-associated ophthalmopathy, the frequency of
      SDHFp antibodies did not appear to be related to the length of time from
      diagnosis: the group containing samples taken less than one year from diagnosis
      showed no increased frequency of SDHFp antibodies when compared to controls (P =
      0.10), with three of the 18 (17%) patients being positive. With respect to seven
      patients with thyroid-associated ophthalmopathy diagnosed for more than a year,
      SDHFp antibodies were not detected in any of their serum samples. In addition,
      the clinical severity of the disease, as recorded by the NOSPECS classification,
      did not correlate with the frequency of SDHFp antibodies: P = 0.13, 0.33 and
      0.38, respectively, for patients with Grade II, III and IV ophthalmopathy.
      Similar results were also found in the case of patients with pretibial myxoedema
      and eye disease: P = 0.06 for patients with Grade III ophthalmopathy and, SDHFp
      antibodies were not detected in any of the sera taken from patients with Grade IV
      ophthalmopathy. In addition, no association was found between disease duration
      and the frequency of antibodies to the flavoprotein in this patient group.
      CONCLUSIONS: Our results indicate that succinate dehydrogenase flavoprotein
      antibodies are not a suitable marker for thyroid-associated ophthalmopathy, at
      least with the assay system used, as they can be found in patients who do not
      have eye disease and therefore lack the disease specificity required of a
      diagnostic tool.

PMID- 10971446
TI  - Dose-response relationship between plasma ACTH and serum cortisol in the insulin
      hypoglycaemia test in 25 healthy subjects and 109 patients with pituitary
      disease.
AB  - OBJECTIVE: The insulin hypoglycaemia test (IHT) is believed to be the most
      reliable test for evaluating the entire hypothalamo-pituitary-adrenal (HPA) axis.
      The lower limit for the normal peak serum cortisol response has been reported to
      be between 500 and 580 nmol/l. Reference levels for a normal plasma ACTH response
      have not been reported recently. DESIGN AND PATIENTS: We performed the IHT in 25
      healthy subjects and in 109 patients with proven or suspected pituitary disorders
      with serial measurements of serum or plasma cortisol and of plasma ACTH, in order
      to establish reference levels and to study the dose-response relationship between
      ACTH and cortisol in this test. In most patients, other pituitary hormonal axes
      were evaluated in addition. RESULTS: With the cortisol kit from Diagnostic
      Products Corporation (DPC), serum cortisol was about 13% lower than plasma (EDTA)
      levels with an excellent correlation between serum and plasma (r = 0.976;
      P<0.001). In the normals, the lower limit of the cortisol response (mean cortisol
      peak level minus 2 SD.) was 570 nmol/l for plasma and 500 nmol/l (calculated) for
      serum, while the lower limit of the ACTH response was 17.6 pmol/l (80 ng/l). In
      normals, the cortisol response was independent of the magnitude of the ACTH
      response. Seventeen out of 30 patients with ACTH responses to levels < 8.8 pmol/l
      (< 40 ng/l) had subnormal cortisol responses. However, 38 of the patients with
      pituitary disease had normal cortisol responses in spite of subnormal ACTH
      responses (group 2), while 47 patients had completely normal IHT results (group
      1). Patients in group 2 had more often additional pituitary hormone deficiencies
      than those of group 1. The dose-response relationship between ACTH and cortisol
      in the patients resembled a dose-response curve that had been set up previously
      in normal subjects who received incremental doses of subcutaneous human ACTH (1
      39). CONCLUSIONS: The normal increment of plasma ACTH in the IHT is greater than
      necessary for stimulating serum cortisol to levels > 500 nmol/l. Patients with a
      subnormal ACTH but normal cortisol response in the IHT have a decreased ACTH
      secretory reserve. It is unlikely that they are at increased risk of developing
      an adrenal crisis perioperatively or in other stressful situations unless
      pituitary function deteriorates. The ACTH-cortisol relationship in the IHT
      performed in patients with pituitary disease shows no sharp dividing line between
      normality and disease, and whether a patient needs permanent glucocorticoid
      substitution is a discretionary decision.

PMID- 10971447
TI  - The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the
      hypothalamic-pituitary-adrenal axis following pituitary surgery.
AB  - OBJECTIVE: To compare the insulin hypoglycaemia test with the short overnight
      metyrapone test in the assessment of the hypothalamic-pituitary-adrenal (HPA)
      axis posthypophysectomy. DESIGN: Prospective comparative study of the insulin
      hypoglycaemia test and the overnight metyrapone test in 32 patients 4-6 weeks
      after pituitary surgery. SUBJECTS: Thirty-two patients with known pituitary
      disease. None with present or previous Cushing's syndrome. OUTCOME MEASUREMENTS:
      Maximum serum cortisol achieved during insulin induced hypoglycaemia compared
      with 0900 hours serum 11-deoxycortisol level following a weight related oral dose
      of metyrapone at 0000 h. RESULTS: One of the 32 patients required further surgery
      and was studied twice after each operation. Thirty-three results are therefore
      compared. Twenty-six of these had a normal cortisol response of 550 nmol/l or
      above leading to the cessation of replacement hydrocortisone. Six of these 26
      patients however, failed the metyrapone test (11-deoxycortisol level less than
      200 nmol/l). After 3-40 months (median 20 months) of follow-up off steroid
      therapy, no patient to date has displayed any clinical evidence of steroid
      deficiency. Of the seven patients who failed the insulin hypoglycaemia test, six
      also failed the metyrapone test. CONCLUSIONS: The overnight metyrapone test
      identified more patients with possible ACTH deficiency than the insulin
      hypoglycaemia test. Further follow-up of these patients is required before a
      final judgement can be made as to whether more subtle but clinically relevant
      ACTH deficiency can be detected by the metyrapone test. Our clinical follow-up to
      date would not support this.

PMID- 10971448
TI  - Effects of normalization of GH hypersecretion on lipoprotein(a) and other
      lipoprotein serum levels in acromegaly.
AB  - BACKGROUND & AIMS: Lipoprotein(a) has been recognized as an important risk factor
      for cardiovascular disease. Lipoprotein(a) has been found to be elevated in sera
      of acromegalic patients, possibly contributing to the increased incidence of
      coronary heart disease found in these patients. In the present study we sought to
      determine the effects of GH hormonal status on lipoprotein(a) and other lipid
      parameters, including lipoprotein lipase (LPL) activity. DESIGN: Cross-sectional
      study. PATIENTS: Twenty acromegalic patients, with either active (n = 12) or
      controlled (n = 8) acromegaly, were studied. Twenty-nine healthy subjects served
      as control group for serum lipid measurements. MEASUREMENTS: Serum GH, IGF-1, IGF
      binding protein-3 (IGFBP-3) and insulin levels were measured in patients. Insulin
      resistance was measured by the homeostatic model assessment (HOMA). Plasma total
      cholesterol, triglycerides, HDL-lipids, apolipoproteins A-I and B, lipoprotein(a)
      and lipoprotein lipase activity were also measured. RESULTS: The highest
      lipoprotein(a) levels were observed in patients with active acromegaly, followed
      by patients with controlled acromegaly, whose lipoprotein(a) concentrations were
      still significantly higher than those of the control group (means +/- SEM: active
      acromegaly, 0.67+/-0.13 g/l; controlled acromegaly, 0.41+/-0.12 g/l; controls
      0.17+/-0.02 g/l; P<0.05). There were no differences in other lipid and
      lipoprotein values among the groups. In patients, significant correlations were
      observed between lipoprotein(a) and basal GH levels (r = 0.56, P<0.02), mean GH
      levels (r = 0.48, P<0.05) and with insulin resistance estimated by HOMA (r =
      0.62, P<0.01). No correlations were found between lipoprotein(a) and IGF-1 or
      IGFBP-3 levels. CONCLUSIONS: Our present results demonstrate that both active
      acromegalic patients and those with controlled disease have elevated serum
      lipoprotein(a) concentrations. The findings might suggest that the present
      biochemical criteria for cure of acromegaly are not strict enough to result in
      the normalization of all the undesirable metabolic changes found in this disease,
      and also that significant cardiovascular risk may persist despite successful
      treatment of acromegaly.

PMID- 10971449
TI  - Postoperative radiotherapy in acromegaly is effective in reducing GH
      concentration to safe levels.
AB  - OBJECTIVE: Several studies have established that in treated acromegaly mortality
      is only normalized in patients achieving a serum GH concentration below 5 mU/l.
      Few studies however, have addressed results of radiotherapy using this strict
      criterion. The aim of our study was to assess the efficacy of postoperative
      radiotherapy in reducing serum GH concentration below 5 mU/l. PATIENTS AND
      METHODS: Forty acromegalic patients who underwent radiotherapy for postoperative
      persistent disease after transsphenoidal surgery were studied. Mean time of
      follow-up after radiotherapy was 123+/-11.1 months. A serum GH concentration of
      <5 mU/l was used to define remission. RESULTS: Following surgery mean GH
      concentration decreased from 120.8+/-21 mU/l to 24.4+/-5.2 mU/l and mean GH
      concentration prior to radiotherapy, administered after a mean of 8.2+/-2.7 (0.5
      96) months postoperatively was 26.0+/-5.1 mU/l. Using individual regression
      plots, GH was reduced to 50% by radiotherapy after a mean of 27+/-5 months (range
      3-105 months). The observed mean GH concentration as measured at follow-up visits
      was reduced by 55% (-36-95%) after the first year, by 65% (-29-97.3%) after 2
      years and by 78% (-29-99%) after 5 years. We could not demonstrate a significant
      correlation between a normalized GH concentration on the one hand and tumour
      size, preradiotherapy GH concentration or duration of follow-up on the other
      hand. During follow-up, GH-suppressive medical therapy was used in 11 patients,
      five of whom were still using medication at the end of follow-up. Eight patients
      had a follow-up of less than 5 years and three of them had a serum GH
      concentration of <5 mU/l at their latest follow-up visit (38%). At 5 years of
      follow-up after radiotherapy, 24 out of 32 patients had a GH level of <5 mU/l
      without medication (75%). At 10 years following irradiation, 16 of 21 patients
      (76%) had a GH level of <5 mU/l without medical treatment. At 15 years follow-up,
      a serum GH concentration of <5 mU/l was observed in 13 out of 15 patients (87%)
      without GH suppressive medication. At the latest follow-up visit, serum GH
      concentration below 5 mU/l was present in 75% of patients (30 out of 40) without
      medical therapy after a mean of 10.4+/-0.9 years, but five patients required
      octreotide up to the end of follow-up. Twenty-seven out of 37 patients with
      available IGF-I data had normal IGF-I at the end of follow-up (73%). Fifty
      percent of patients needed substitution therapy for (partial) hypopituitarism
      after 10 years and 75% after 15 years of radiotherapy. CONCLUSION: In our group
      of patients who were incompletely cured by surgery, but had a significant
      postoperative decrease of serum GH concentrations, radiotherapy was able to
      achieve 'safe' serum GH concentrations in the majority in the long term.

PMID- 10971450
TI  - Monitoring serum insulin-like growth factor-I (IGF-I), IGF binding protein-3
      (IGFBP-3), IGF-I/IGFBP-3 molar ratio and leptin during growth hormone treatment
      for disordered growth.
AB  - OBJECTIVE: Serum IGF-I levels are monitored during GH replacement treatment in
      adults with GH deficiency (GHD) to guide GH dose adjustment and to minimize
      occurrence of GH-related side-effects. This is not routine practice in children
      treated with GH. The aim of this study was to evaluate changes in (1) serum IGF
      I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio, and (2) serum leptin, an indirect
      marker of GH response, during the first year of GH treatment in children with
      disordered growth. DESIGN: An observational prospective longitudinal study with
      serial measurements at five time points during the first year of GH treatment was
      carried out. Each patient served as his/her own control. PATIENTS: The study
      included 31 patients, grouped as (1) GHD (n = 20) and (2) non-GHD (Turner
      syndrome n = 7; Noonan syndrome n = 4), who had not previously received GH
      treatment. MEASUREMENTS: Serum IGF-I, IGFBP-3 and leptin levels were measured
      before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH
      treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non-GHD
      groups. IGF-I, IGFBP-3 and the calculated IGF-I/IGFBP-3 molar ratio were
      expressed as SD scores using reference values from the local population. RESULTS:
      In the GHD group, IGF-I SDS before treatment was lower compared with the non-GHD
      (-5.4+/-2.5 vs. -1.8+/-1.0; P<0.001). IGF-I (-1.8 SDS +/- 2.2) and IGFBP-3 (-1.1
      SDS +/- 0.6) levels and their molar ratios were highest at 6 weeks and remained
      relatively constant thereafter. In the non-GHD group, IGF-I levels increased
      throughout the year and were maximum at 12 months (0.3 SDS +/- 1.4) while IGFBP-3
      (1.1 SDS +/- 0.9) and IGF-I/IGFBP-3 molar ratio peaked at 6 months. In both
      groups, IGF-I SDS and IGF-I/IGFBP-3 during treatment correlated with the dose of
      GH expressed as IU/m2/week (r-values 0. 77 to 0.89; P = 0.005) but not as
      IU/kg/week. Serum leptin levels decreased significantly during GH treatment in
      the GHD (median before treatment 4.0 microg/l; median after 12 months treatment
      2.4 microg/l; P = 0.02) but not the non-GHD (median before treatment 3.0
      microg/l; median after 12 months treatment 2.6 microg/l). In the GHD group, serum
      leptin before treatment correlated with 12 month change in height SDS (r = 0.70,
      P = 0.02). CONCLUSIONS: The pattern of IGF-I, IGFBP-3 and their molar ratio
      during the first year of GH treatment differed between the GHD and non-GHD
      groups. Calculation of GH dose by surface area may be preferable to calculating
      by body weight. As a GH dose-dependent increase in serum IGF-I and IGF-I/IGFBP-3
      may be associated with adverse effects, serum IGF-I and IGFBP-3 should be
      monitored routinely during long-term GH treatment. Serum leptin was the only
      variable that correlated with first year growth response in GHD.

PMID- 10971451
TI  - Expression analysis of cyclins in pituitary adenomas and the normal pituitary
      gland.
AB  - OBJECTIVES: The molecular events involved in pituitary tumour development are
      still poorly understood. The cyclins play an important role in the control of the
      cell cycle during cell proliferation and over-expression of the cyclins has been
      shown in many different tumour types. The aim of this study was to investigate
      whether, in comparison to the normal gland, ectopic expression of cyclins occurs
      in pituitary tumours, and whether differences in cyclin expression are seen with
      different pituitary tumour types or in association with different tumour
      behaviour. In contrast to work on cyclin D there are no published data on cyclin
      B, A and E in human pituitary tumours. METHODS: Sixty-seven surgically removed
      pituitary tumours and 10 specimens of normal human anterior gland were studied
      using immunohistochemistry to detect the nuclear expression of cyclin A, B, D and
      E. The microvascular density (as a measure of angiogenesis), Ki-67 labelling
      index (to assess cell proliferation) and bcl-2 expression had previously been
      investigated in this cohort. RESULTS: All tumours studied contained cells that
      immunostained positively for cyclin A, B, D and E. However the proportion of
      positive cells in each tumour type was different. In contrast, there were no
      cyclin D positive cells in the normal anterior pituitary gland studied, and
      labelling indices (LI) for cyclins A, B and E were significantly lower in the
      normal gland than in pituitary adenomas. The cyclin LIs for A, B, D and E were
      significantly higher in macroadenomas when compared to microadenomas. Non
      functioning pituitary tumours (NFA) generally showed the highest cyclin LI. In
      particular, both recurrent and nonrecurrent NFA showed significantly higher
      cyclin D LI than other tumours. The ratio of cells expressing cyclin B compared
      to those expressing cyclin A was significantly higher in functionless tumours
      that regrew when compared to NFAs that did not (P<0.05). Cyclin D LI and the
      overall Ki-67 LI as a measure of cell proliferation were related (R2 = 11.4, P =
      0.0033) and bcl-2 positive tumours had significantly higher cyclin D LI compared
      with bcl-2 negative tumours. There was a weak relationship between angiogenesis
      and the relative proportion of cells expressing D when compared to those in S
      phase (D/A ratio) (r2 = 10.5, P = 0.02). CONCLUSIONS: We have demonstrated that
      ectopic expression of cyclin D and over-expression of cyclins A, B and E,
      regulating different stages of the cell cycle is common in pituitary adenomas. In
      addition, cyclin expression was related to size and to pituitary tumour regrowth.
      The differences between functionless tumours that regrow and those that do not,
      may be due to reduced bcl-2 expression, increased cell proliferation, more cells
      at the G2/M stage (B/A ratio) and reduced cell differentiation with more
      aggressive subsequent tumour behaviour. Cyclin D expression and cell
      proliferation were related indicating that the cells entering the cycle become
      'committed' to cell cycle progression. There was no relative over-expression of
      individual cyclins, and therefore no evidence of relative increase in cell cycle
      phase, indicating that the increased cyclin expression is more likely to be due
      to constant mitogenic stimulation rather than cell cycle regulatory failure.
      Although nuclear cyclin expression is a good marker of tumour growth and
      aggressive behaviour, the growth signal that leads to cyclin expression remains
      to be identified.

PMID- 10971452
TI  - Corpus luteum response to exogenous HCG during the mid-luteal phase of the
      menstrual cycle.
AB  - OBJECTIVE: To assess a range of exogenous HCG regimes designed to simulate the
      endocrine environment occurring in biochemical, single and multiple pregnancies
      and to study the response of the corpus luteum to those regimes. DESIGN:
      Prospective clinical study. PATIENTS: Twenty-five normally cycling women aged 24
      35 years were given one of four regimes of HCG injections designed to mimic the
      HCG concentrations found following spontaneous implantation. Regimes A, B, C and
      D were designed with starting HCG doses of 60, 140, 250 and 1000 iu,
      respectively. The daily HCG injections were then increased to give a doubling
      concentration every 30 h for regime A, every 27 h for regime B, every 24 h for
      regimes C and D. HCG administration was started on either days 7 or 8 after the
      LH peak. MEASUREMENTS: Plasma HCG and progesterone concentrations. RESULTS:
      Subjects given regime A failed to demonstrate any rescue of the corpus luteum
      despite low-detectable amounts of HCG in the circulation equivalent to those seen
      in some biochemical pregnancies. In contrast, subjects given regimes B and C
      demonstrated prompt increases in progesterone secretion immediately after the
      first HCG injection achieving HCG and progesterone concentrations in plasma
      similar to those seen in normal singleton pregnancies. Subjects given regime D
      also showed rapid rescue of the corpus luteum but this time achieved plasma HCG
      concentrations in the range normally seen in multiple pregnancies. All subjects
      in regimes B, C and D secreted significantly higher amounts of progesterone than
      those in regime A (P<0.001). However, despite the greater amounts of HCG used in
      regime D, the amount of progesterone produced was not significantly different
      from regimes B or C. CONCLUSIONS: The exogenous HCG regimes used in this study
      successfully mimicked the hormonal environment found in biochemical, single and
      multiple pregnancies and elicited appropriate corpus luteum responses.

PMID- 10971453
TI  - Potential of norethisterone enanthate for male contraception: pharmacokinetics
      and suppression of pituitary and gonadal function.
AB  - OBJECTIVE: Gestagens are known to suppress gonadotrophins in women and are
      currently also under investigation for the development of hormonal male
      contraceptives. The aim of the study was to assess the potential of
      norethisterone enanthate (NETE) for male contraception. DESIGN AND MEASUREMENTS:
      The suppressive effect of a single injection of 200 mg NETE on serum
      gonadotrophins, serum testosterone, lipids, spermatogenesis, well-being and
      sexual function was evaluated in seven healthy men. RESULTS: In this single dose
      study treatment was well tolerated by all volunteers. NETE led to a rapid,
      profound and significant suppression of serum LH (day 6 - day 10), FSH (day 2 -
      day 29), testosterone (day 1 - day 29 and day 35) and SHBG (day 6 - day 35). At
      study end sperm counts were significantly suppressed. Numbers of spontaneous
      erections (day 17, 23 and 26), number of sexual fantasies (day 20 and 23) as well
      as libido (day 20 and 26) were significantly decreased compared to baseline. All
      other parameters including lipids, augmented glucose, testicular volume and well
      being showed no significant alterations. CONCLUSION: Because of its strong, rapid
      and sustained suppression of serum FSH and testosterone norethisterone enanthate
      offers great potential for hormonal male contraception if combined with
      testosterone esters.

PMID- 10971454
TI  - Cardiovascular risk markers in hypothalamic amenorrhoea.
AB  - OBJECTIVE: To determine whether women with oestrogen deficiency due to
      hypothalamic amenorrhoea (HA) would demonstrate a lipid and lipoprotein pattern
      similar to that seen in menopause with higher total cholesterol (TC), LDL,
      triglyceride and Lp(a) and lower HDL levels than women with regular menstrual
      cycles. DESIGN: Cross-sectional. PATIENTS: Fifty subjects: 21 women with HA and
      30 eumenorrhoeic controls (NL) matched for age, BMI and fat-free mass.
      MEASUREMENTS: Lipid and lipoprotein levels. RESULTS: There was a significant
      difference in Lp(a) levels in the HA group between women with >19% fat intake and
      those <19% fat intake (352+/-231 vs. 116+/-62 mg/l, P = 0.006). Percent fat
      intake was the most significant determinant of Lp(a) levels in HA, accounting for
      51% of the variation in Lp(a) levels. Mean HDL levels were higher in the women
      with HA compared with the controls (1.3+/- 0.3 vs. 1.1+/-0.2 mmol/l, P = 0.002).
      There was no significant difference between the groups in TC [4.4+/-0.9 (HA) vs.
      4.1+/-0.8 mmol/l (NL), P>0.05], LDL [2.8+/-0.6 (HA) vs. 2.7+/-0.7 mmol/l (NL),
      P>0.05], triglycerides [1.8+/-0.5 (HA) vs. 1.7+/-0.5 mmol/l (NL), P>0.05] or
      Lp(a) [234+/-199 (HA) vs. 247+/-222 (NL) mg/l, P>0.05] levels. CONCLUSION:
      Reduced Lp(a) levels were associated with low dietary fat in women with HA.
      Moreover, in contrast to menopausal oestrogen deficiency, young women with HA and
      oestrogen deficiency have increased levels of HDL and no increases in TC, LDL and
      triglycerides. These data suggest that the negative effects of oestrogen
      deficiency on cardiovascular risk factors may be modified in women with
      hypothalamic amenorrhoea.

PMID- 10971455
TI  - Influence of exogenous melatonin on catecholamine levels in postmenopausal women
      prior and during oestradiol replacement.
AB  - OBJECTIVE: In young individuals melatonin administration reduces circulating
      norepinephrine. Some effects of melatonin are reduced in elderly women and are
      modulated by gonadal steroids. Accordingly, the influence of melatonin on
      catecholamine levels was investigated in postmenopausal women without and with
      oestradiol replacement. DESIGN: Prior to and after 2 months of transdermal
      oestradiol (50 microg/day), women were studied on two consecutive days, on which
      they received placebo or 1 mg of melatonin orally in a randomised and double
      blind fashion. PATIENTS: Fourteen healthy postmenopausal women. MEASUREMENTS:
      Resting levels of epinephrine and norepinephrine and their responses to both a
      cold stimulus, performed by placing a hand in a basin of water and ice for 2
      minutes, and to 10 minutes of upright position (upright test). RESULTS: Prior to
      oestradiol, melatonin did not modify baseline or stimulated catecholamine levels.
      In contrast, during oestradiol, melatonin tended to reduce, although not
      significantly, baseline norepinephrine levels (P = 0.053), and significantly
      reduced peak values (P = 0.0061) and integrated norepinephrine response (P =
      0.0076) to the cold stimulus. Responses of norepinephrine to the upright test
      were not modified, while those of epinephrine were increased (P = 0.042). During,
      but not prior to oestradiol replacement, modifications induced by melatonin
      (melatonin day-placebo day) in the norepinephrine response to the cold (r2 = 0.
      457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and
      inversely related to the responses of the placebo day. CONCLUSIONS: Melatonin
      does not modulate adrenergic activity in postmenopausal women without hormone
      replacement therapy. Oestradiol replacement restores the capability of melatonin
      to modulate adrenergic activity, particularly the norepinephrine response to
      stimuli.

PMID- 10971456
TI  - Reduced vitamin D receptor expression in parathyroid adenomas: implications for
      pathogenesis.
AB  - BACKGROUND AND OBJECTIVES: Parathyroid adenomas discovered fortuitously grow very
      slowly and their cell birth rate greatly declines, features explicable by an
      initial increase in secretory set-point. In the nodules of severe uraemic
      parathyroid hyperplasia, there is an increased set-point and decreased expression
      of both the calcium sensing receptor (CaSR) and the vitamin D receptor (VDR).
      Accordingly, we examined VDR and CaSR expression in parathyroid adenomas.
      PATIENTS AND DESIGN: We studied 24 patients with primary hyperparathyroidism with
      a wide range of vitamin D nutritional status (plasma 25-hydroxyvitamin D range 10
      107 nmol/l). Eighteen patients discovered by biochemical screening were enrolled
      in a natural history or treatment option study, and six additional US patients
      matched a group studied concurrently in India with low plasma 25-hydroxyvitamin D
      level (< 37 nmol/l). MEASUREMENTS: Receptor expression was determined by
      immunocytochemistry in each tumour and in 11 cases also in adjacent
      nonadenomatous tissue. VDR expression was reported as the proportion of positive
      cells (strongly rather than weakly stained) determined by systematic random
      sampling and CaSR expression as grey scale values of staining intensity in
      arbitrary units determined by image analysis. RESULTS: The mean (SD) proportion
      of cells positive for VDR was 2.93 (2.17)% in the parathyroid adenomas and 95.7
      (5.10)% in the nonadenomatous tissue. In about two-thirds of the cases VDR
      positive cells could have been remnants of a normal gland, but in the remaining
      one-third they were too numerous to be accounted for by this explanation. The
      mean (SD) intensity of CaSR expression was 151 (4.71) units in parathyroid
      adenomas and 218 (5.0) units in nonadenomatous tissue (P<0.001). The frequency of
      VDR loss and the changes in CaSR immunohistochemistry were unrelated to race,
      sex, or disease severity, except that the reduction in CaSR was significantly
      greater in patients with normal vitamin D nutrition (32.1% vs. 29.0%).
      CONCLUSIONS: (1) There is reduction of vitamin D receptor expression in almost
      all cells in parathyroid adenomas. This defect was probably present in the
      founder cell of the tumour clone in the majority of cases. Since mutations in the
      vitamin D receptor gene have been sought but not found, possible explanations
      include inhibition of vitamin D receptor gene transcription, decreased amount of
      the corresponding mRNA, or failure of normal translation. (2) Reduction in
      calcium sensing receptor could be either the primary defect or (more commonly)
      secondary to loss of vitamin D receptor and is of sufficient magnitude to account
      for the increase in secretory set-point and consequent asymptotic growth and
      stable clinical course.

PMID- 10971457
TI  - Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF
      receptors in patients with bulimia nervosa.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous
      immunological and metabolic activities. In addition, TNF-alpha can stimulate a
      variety of physiological, neuroendocrine and behavioural responses of the central
      nervous system. In experimental animals, TNF-alpha induces changes in
      physiological and behavioural parameters which have also been observed in eating
      disorders. The biological activities of TNF-alpha are mediated by two
      structurally related, but functionally distinct receptors, TNF-RI and TNF-RII.
      Since injection of TNF-alpha results in increased shedding of TNF-alpha
      receptors, it is likely that TNF-alpha release is reflected by soluble TNF
      receptors (sTNF-Rs) levels. AIMS: We studied plasma concentrations of TNF-alpha
      and two sTNF-Rs (sTNF-RI and sTNF-RII) in female patients with bulimia nervosa.
      DESIGN AND PATIENTS: Twenty female patients with bulimia nervosa (BN) and 20 age
      matched normal women (N) were studied. MEASUREMENTS: Plasma TNF-alpha
      concentrations were measured by enzyme immunoassay kit and plasma concentrations
      of sTNF-RI and sTNF-RII were measured by enzyme-linked immunosorbent assay.
      RESULTS: Plasma TNF-alpha concentrations in BN were significantly higher than
      those in N (4.7+/- 0.5 ng/l vs. 1.6+/-0.1 ng/l; P<0.01). Although no significant
      difference was observed in plasma sTNF-RI concentrations between the two groups,
      plasma sTNF-RII concentrations in BN were significantly higher than those in N
      (2080.0+/-107.5 ng/l vs. 1569.5 +/-84.0 ng/l; P<0.01). Plasma TNF-alpha
      concentrations were significantly related to plasma sTNF-RI concentrations (r =
      0.511, P<0.05) and to plasma sTNF-RII concentrations (r = 0.532, P<0.05) in
      bulimic patients. However, plasma TNF-alpha concentrations were not related to
      body fat mass or to bulimic behaviours in these patients. CONCLUSIONS: Our
      present findings suggest that the adipose tissue may not be the immediate source
      of TNF-alpha in bulimic patients but the increase in plasma TNF-alpha in these
      patients may be derived from the central nervous system sources. The elevated
      sTNF-RII may reflect different shedding kinetics compared with sTNF-RI in bulimic
      patients.

PMID- 10971458
TI  - Novel mutations of the ACTH receptor gene in a female adult patient with adrenal
      unresponsiveness to ACTH.
AB  - We report a 30-year-old female with adrenal unresponsiveness to ACTH. Her
      clinical features included no adrenal crisis despite poor drug compliance, poor
      pubic hair development (Tanner stage 2), well-developed breasts (Tanner stage 5),
      and regular menstrual cycles. Endocrinological data included blood ACTH 1500
      pmol/l, cortisol 18 nmol/l, dehydroepiandrosterone sulphate below 0.26
      micromol/l, activated renin 0.37 pmol/l, and aldosterone 3.4 nmol/l. Direct
      sequencing and allele-specific amplification revealed two novel mutations in the
      ACTH receptor gene. One was transition from guanine to adenine at nucleotide
      position 1002, resulting in substitution of aspartate for asparagine at codon
      103, and the other was transition from cytosine to thymine at nucleotide 1104,
      leading to substitution of arginine for tryptophan at codon 137. The present
      findings lend additional credence to the notions that adrenal androgens play an
      important role in female pubic hair development and that ovarian development
      takes place independently of adrenarche.

PMID- 10971460
TI  - Magnetization transfer technique: a new diagnostic tool for the postoperative
      assessment of pituitary adenomas.

PMID- 10971459
TI  - A new missense mutation in the calcium-sensing receptor in familial benign
      hypercalcaemia associated with partial lipoatrophy and insulin resistant
      diabetes.
AB  - We studied two patients (a 54-year-old woman and her 16-year-old son) with
      familial benign hypocalciuric hypercalcaemia (FBHH) associated with severe
      insulin resistant diabetes in the context of a partial lipodystrophic syndrome.
      Sequencing of the entire coding sequence of the calcium-sensing receptor (CaR)
      gene revealed a novel heterozygous mutation at codon 395, leading to the
      substitution of a cysteine by an arginine residue (Cys395Arg) in the
      extracellular ligand-binding domain. This mutation was absent in two
      normocalcaemic relatives and in 54 control subjects. It was recently shown, in
      transfection studies, that the substitution of this amino acid results in
      incomplete receptor processing, a severe decrease in cell surface expression and
      altered signal transduction (Fan et al., 1998). This mutation is therefore likely
      to be responsible of the FBHH phenotype. A pathophysiological link between this
      mutation and insulin resistance remains unclear.

PMID- 10971461
TI  - Chronic allergen challenge as an experimental model: necessary, significant or
      useful?

PMID- 10971462
TI  - Asthma and MIF: innately Th1 and Th2.

PMID- 10971463
TI  - Microenvironmental influences in atopic disease.

PMID- 10971464
TI  - The role of pulmonary surfactant in the asthmatic response.

PMID- 10971465
TI  - Human mast cells and basophils as sources of cytokines.

PMID- 10971466
TI  - Species differences in adenosine receptor-mediated bronchoconstrictor responses.

PMID- 10971467
TI  - A review of antigen diversity causing lung disease among pigeon breeders.

PMID- 10971468
TI  - Exposure to endotoxin or other bacterial components might protect against the
      development of atopy.
AB  - BACKGROUND: Several recent studies have shown that growing up on a farm confers
      significant protection against the development of atopy. These findings point
      particularly towards the importance of exposure to stable dust and farm animals.
      It has furthermore been reported that endotoxin, an intrinsic part of the outer
      membrane of gram negative bacteria, is abundant in environments where livestock
      and poultry is kept. The aim of this study was therefore to measure the level of
      environmental endotoxin exposure in homes of farmers' children, children with
      regular contact to livestock and control children with no contact to farm
      animals. METHODS: Eighty-four farming and nonfarming families were identified in
      rural areas in Southern Germany and Switzerland. Samples of settled and airborne
      dust were collected in stables, and of settled dust indoors from kitchen floors
      and the children's mattresses. Endotoxin concentrations were determined by a
      kinetic Limulus assay. RESULTS: Endotoxin concentrations were highest in stables
      of farming families, but were also significantly higher indoors in dust from
      kitchen floors (143 EU/mg vs 39 EU/mg, P < 0.001) and children's mattresses
      (49479 EU/m2 vs 9383 EU/m2, P < 0.001) as compared to control children from
      nonfarming families. In addition, endotoxin levels were also significantly higher
      in mattresses and dust from kitchen floors in households where children had
      regular contact to farm animals (38.6 EU/mg and 23340 EU/m2, respectively) as
      compared to control subjects. CONCLUSION: We propose that the level of
      environmental exposure to endotoxin and other bacterial wall components is an
      important protective determinant for the development of atopic diseases in
      childhood.

PMID- 10971469
TI  - Effects of once daily dosing with inhaled budesonide on airway
      hyperresponsiveness and airway inflammation following repeated low-dose allergen
      challenge in atopic asthmatics.
AB  - BACKGROUND: Repeated low-dose allergen challenge increases airway
      hyperresponsiveness and sputum eosinophils in atopic asthmatics. Inhaled
      corticosteroids attenuate the airway responses to high-dose allergen challenge,
      but have not been evaluated against repeated low dose challenge. OBJECTIVE: This
      study evaluates the effects of once daily treatments of two doses of inhaled
      budesonide on airway responses to repeated low-dose allergen challenge. METHODS:
      Eight atopic asthmatics with a dual airway responses to inhaled allergen were
      recruited into a randomized, double-blind crossover, placebo-controlled study. In
      the mornings of four consecutive days (day 1-day 4), subjects inhaled budesonide
      100 microg, 400 microg, or placebo, 30 min before inhaling a concentration of
      allergen causing a 5% early fall in FEV1. Airway hyperresponsiveness to
      methacholine and sputum eosinophils were measured at baseline, on the afternoon
      of day 2, day 4, and 24 h after the last challenge. There was a 1-week washout
      between each of the three treatment periods. RESULTS: The repeated low-dose
      allergen challenge induced increases in the percentage sputum eosinophils from
      2.0 +/- 0.7% at baseline to 16.6 +/- 7.1% on day 4 (P = 0.002), and this effect
      was reduced by once daily budesonide 100 microg to 5.6 +/- 1.8% (P = 0. 01) and
      by once daily budesonide 400 microg to 3.1 +/- 0.9% (P = 0. 004). Also, the
      allergen-induced methacholine airway hyperresponsiveness which occurred by day 4
      (P = 0.03) of the repeated low dose challenge was inhibited by budesonide 400
      microg (P = 0.017). CONCLUSION: Both budesonide 100 microg and 400 microg inhaled
      once daily significantly reduces allergen-induced sputum eosinophilia after
      repeated low dose challenge; however, only the higher dose also attenuates the
      allergen-induced airway hyperresponsiveness.

PMID- 10971470
TI  - Macrophage migration inhibitory factor (MIF) in bronchial asthma.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory
      cytokine favouring the secretion of TNFalpha and IL-8 and counteracts anti
      inflammatory effects of corticosteroids. Airways inflammation is a central
      feature of bronchial asthma and is characterized by the accumulation of
      eosinophils. OBJECTIVE: The aim of this study was to investigate whether MIF is
      related to asthma symptoms and eosinophil accumulation in the airways. METHODS:
      Serum MIF levels were measured by an enzyme-linked immunosorbent assay in 44
      healthy subjects and 44 asthmatics. Levels of MIF in induced sputum were measured
      in 10 healthy subjects and 15 asthmatics. Levels of eosinophil cationic protein
      (ECP) in induced sputum were measured by a radioimmunosorbent assay. Fluorescence
      double immunostaining was conducted to examine cellular source and localization
      of MIF. RESULTS: Serum MIF levels were significantly increased in asthmatic
      patients compared with age and sex-matched control subjects. Symptomatic patients
      had a higher MIF level than asymptomatic patients. Induced sputum obtained from
      asthmatics contained higher levels of MIF than those from control subjects. MIF
      levels in induced sputum were correlated with ECP levels in induced sputum. MIF
      was colocalized with eosinophil peroxidase staining in the cytoplasm of sputum
      cells. CONCLUSION: Increased MIF levels are associated with asthma symptoms and
      one of the cellular sources of MIF in the airways are eosinophils.

PMID- 10971471
TI  - Reduced IFNgamma production in response to IL-12 stimulation and/or reduced IL-12
      production in atopic patients.
AB  - BACKGROUND: Several studies have shown that interleukin (IL)-4 and interferon
      gamma (IFNgamma) are important for the regulation of IgE production and that IL
      12 induces IFNgamma. OBJECTIVE: IFNgamma production in response to IL-12
      stimulation and IL-12 production were investigated in peripheral blood
      mononuclear cells (PBMCs) of atopic patients with various levels of serum IgE.
      METHODS: Cytokine production from PBMCs was measured following stimulation with a
      nonspecific stimulator (phytohemagglutinin: PHA), a specific stimulator (Der f 1)
      and IL-12 in 17 healthy controls and 23 atopic patients with various serum IgE
      levels. RESULTS: The IFNgamma production by IL-12-stimulated PBMCs in the atopic
      group was lower than that in the control group. Furthermore, the serum IgE level
      was negatively correlated with IFNgamma production by PBMCs stimulated with IL-12
      (P < 0.001), and with IL-12 production by PBMCs stimulated with Der f 1 (P <
      0.001). Although the IFNgamma concentrations by PHA-stimulated PBMCs were
      correlated with those by IL-12-stimulated PBMCs, there were differences in
      several patients. CONCLUSIONS: Our results indicated that atopic patients may
      have some abnormality in the IL-12-IFNgamma loop. It was shown that the elevation
      in IgE levels in atopic patients may be due to reduced IFNgamma production in
      response to IL-12 stimulation and/or due to reduced IL-12 production.

PMID- 10971472
TI  - Endogenous glucocorticoids and antigen-induced acute and late phase pulmonary
      responses.
AB  - BACKGROUND: Several studies suggest that endogenous glucocorticoids can dampen
      the severity of experimental allergic reactions in animals. OBJECTIVE: To
      investigate the influence that endogenous glucocorticoids have on the course of
      IgE-mediated pulmonary early and late phase reactions. METHODS: Twenty-one
      allergic asthmatic and six healthy control subjects underwent inhaled antigen
      challenge with measurements of plasma cortisol and cortisone by gas
      chromatography-mass spectrometry. RESULTS: There were no differences between the
      asthmatic and control groups in the baseline levels of cortisol or cortisone.
      However, the asthmatic subjects had significantly higher cortisol levels (67.2 +/
      8.6 vs 35.1 +/- 4.5 ng/mL; P = 0.04) and had higher cortisol/cortisone ratios
      (4.8 +/- 0. 6 vs 3.0 +/- 0.2; P = 0.01) 8 h after challenge compared to the
      control subjects. Among the asthmatic subjects, those whose FEV1 recovered
      rapidly had higher baseline levels of cortisol and those who displayed a late
      phase reaction had lower levels of cortisol during the late phase period.
      CONCLUSION: The results suggest that endogenous glucocorticoids may play a
      significant role in the modulation of airway responses to antigen challenge, and
      that antigen challenge may induce cortisol production in allergic subjects.

PMID- 10971473
TI  - Suppression of neural activity of bronchial irritant receptors by surface-active
      phospholipid in comparison with topical drugs commonly prescribed for asthma.
AB  - BACKGROUND: Much indirect evidence has been put forward previously in support of
      the concept that surface-active phospholipid (SAPL) normally masks irritant
      receptors in the lungs and upper respiratory tract; but this physical barrier is
      deficient in asthmatics, imparting hyperresponsiveness of the bronchoconstrictor
      reflex. OBJECTIVE: To determine whether exogenous SAPL applied to bronchial
      mucosa reduces the sensitivity of irritant receptors to a standard challenge used
      clinically to diagnose asthma and to compare the effects with those of
      corticosteroids and beta-stimulation. METHODS: Nerve fibres in the vagi were
      monitored to record action potentials from irritant receptors identified in the
      upper airways of rat lungs in response to a methacholine challenge. SAPL in the
      form of dipalmitoyl phosphatidylcholine (PC) and phosphatidylglycerol (PG) - 7 :
      3 PC:PG - was applied as a fine dry powder to enhance surface activity and,
      hence, chemisorption to epithelium. Comparison was also made with clinical doses
      of i.v. hydrocortisone and instilled salbutamol together with liquid or solid
      controls, as appropriate. RESULTS: Neural activity of irritant receptors was
      found to be significantly (P = 0.0018) decreased by topical SAPL by 35.8% in
      response to a methacholine challenge in contrast to an increase of 11.2% in
      response to a solid (lactose) control. Instilled salbutamol and i.v.
      hydrocortisone also decreased responses to the same challenge by 43.4% and 14.7%,
      respectively, in contrast to a liquid (saline) control which increased by 24.5%.
      CONCLUSIONS: Surface-active phospholipid has an appreciable effect upon irritant
      receptors in rat airways, reducing neural response to a methacholine challenge by
      an amount comparable to that of Salbutamol. These results support the concept of
      SAPL masking bronchial irritant receptors and warrant placebo-controlled clinical
      trials of this dry powder as a means of controlling asthma without the side
      effects of current medication. Other possible roles discussed for the SAPL
      epithelial barrier include the exclusion of viruses and allergens.

PMID- 10971474
TI  - Regulation of cyclooxygenase-1 and -2 expression in human nasal mucosa. Effects
      of cytokines and dexamethasone.
AB  - BACKGROUND: Cyclooxygenase (COX) converts arachidonic acid in prostanoids. COX
      exists in two isoforms, COX-1 is the constitutive whereas COX-2 is the inducible
      isoform. The regulation of COX-1 and COX-2 expression in nasal mucosa has not
      been previously reported. AIM: We studied expression and regulation by cytokines
      and corticosteroids of COX-1 and COX-2 in human nasal mucosa. Cultured human
      nasal explants from patients undergoing corrective nasal mucosal resection were
      examined for COX-1 and COX-2 expression by semiquantitative competitive PCR and
      Western blot. METHODS: Explants were incubated with pro-(IFNgamma, IL-1beta, and
      TNF-alpha) and anti(IL-10) inflammatory cytokines and dexamethasone. The
      mechanisms which regulate COX-2 mRNA expression were studied using inhibitors of
      translation (Actinomycin D) and transcription (Cicloheximide). RESULTS: The
      baseline expression of COX-2 mRNA was higher than COX-1 mRNA. Once in culture,
      there was a slight spontaneous up-regulation of COX-1 and a strong COX-2 mRNA and
      protein up-regulation. The incubation of nasal explants with pro-inflammatory
      cytokines increased the expression of COX-2 mRNA and protein, from 1 to 24 h of
      incubation in a dose-related manner. The regulation of these effects occurred at
      both transcriptional and post-transcriptional levels. Dexamethasone and IL-10
      abrogated cytokine-induced COX-2 mRNA and protein expression. Pro-inflammatory
      cytokines, dexamethasone and IL-10 had no effect on COX-1 mRNA expression.
      CONCLUSIONS: As prostanoids have important regulatory effects on the
      immunologically mediated inflammatory responses, our findings throw some light on
      the mechanisms that regulate the enzymes which produce these metabolites in the
      human airway.

PMID- 10971475
TI  - Recombinant Hev b 1: large-scale production and immunological characterization.
AB  - BACKGROUND: Hev b 1 represents one of the most important allergens in Hevea
      brasiliensis latex. It is difficult to get an appropriate amount of native Hev b
      1 (nHev b 1) for research purposes. OBJECTIVE: The aim of this study was to
      produce sufficient amounts of Hev b 1 by recombinant methods to prove its
      suitability for latex allergy diagnostics. METHODS: We isolated total RNA of
      Hevea brasiliensis leaves and synthesized cDNA by RT PCR. Recombinant Hev b 1
      (rHev b 1) as well as three fragments (amino acid residues 29-137, 48-137, 78
      137) were subcloned and expressed as fusion proteins with Maltose-binding protein
      (MBP) in Escherichia coli. The MBP-rHev b 1 fusion protein was examined by RAST
      with the CAP method, histamine release test and immunoblots with human sera from
      spina bifida patients as well as from health care workers with latex allergy and
      monoclonal antibodies. RESULTS: Histamine release test and immunoblots revealed
      the high allergenicity of the MBP-rHev b 1 construct. By the CAP method, 54 out
      of 58 serum samples (93%) from latex-sensitized spina bifida patients previously
      showing immunoglobulin (Ig) E to nHev b 1 exhibited IgE-binding to rHev b 1.
      Among 71 latex-allergic health care workers tested, 16 (22.5%) had IgE antibodies
      to rHev b 1. The analysis of the fusion proteins carrying rHev b 1 fragments
      revealed that the loss of the N-terminal 28 amino acid residues did not affect
      IgE-binding. In contrast, the lack of the first 47 amino acid residues led to
      decreased IgE-binding reactivity in two out of four sera tested, whereas the
      absence of the N-terminal 77 residues abolished IgE-binding in these two sera.
      CONCLUSION: The MBP-rHev b 1 fusion protein exhibits a corresponding IgE-binding
      reactivity to nHev b 1 and may therefore substitute natural Hev b 1 for both in
      vitro diagnostics and research purposes.

PMID- 10971476
TI  - Localization of a major allergen, Der p 2, in the gut and faecal pellets of
      Dermatophagoides pteronyssinus.
AB  - BACKGROUND: The house dust mite Dermatophagoides ptronyssinus is one of the most
      significant indoor sensitizing agents of allergy. Allergen localization may
      indicate the importance of secreted materials, faeces, and nonexcreted mite body
      components as allergen sources. OBJECTIVE: This study attempted to localize the
      sites and concentrations of Der p 2 in the cryostat sections of D. pteronyssinus
      using antirecombinant Der p 2 monoclonal antibody. METHODS: Male and female mites
      and mite faeces collected separately from both sexes were used. Live mites were
      embedded and serial cryostat sections for light microscopy were performed. Anti
      recombinant Der p 2 monoclonal antibody previously produced by the authors was
      used. For immunoprobing, mite cryostat sections were incubated in the following
      antibody-containing solutions: monoclonal antibody against Der p 2 was initially
      applied to the sections and fluorescent isothiocyanate conjugated antimouse
      immunoglobulin G was reacted as the secondary antibody. The faecal pellets were
      treated the same as described above. RESULTS: Immunofluorescent probing of
      cryostat sections with the monoclonal antibody showed labelling of the gut
      lining, gut contents and defecated faecal pellets. No other internal organs were
      identified as positively labelled. CONCLUSION: This study suggested that a major
      allergen, Der p 2, found in the house dust mite D. pteronyssinus is derived from
      the digestive tract and concentrated in the faeces.

PMID- 10971477
TI  - Rapid polarization of Th2 cells during induction of antigen-specific IgE
      antibodies in vitro.
AB  - BACKGROUND: Type 2 T-helper cells (Th2) are involved in the regulation of the
      humoral immune response against antigens and allergens and directly affect which
      isotype will be produced. The mechanism that regulates antigen-specific IgE
      secretion and immune deviation is still not known. OBJECTIVES: To delineate
      mechanisms behind antigen-specific IgE secretion we have used in vitro
      immunization and focused on T-cell phenotype and the activation status of the
      transcription factor NFkappaB. METHODS: Peripheral blood lymphocytes (PBMC) from
      seronegative donors were immunized in vitro with a peptide consisting of both a T
      cell and a B-cell epitope. RESULTS: Antigen-specific IgE antibodies could be
      detected after a primary immunization, during which T-helper cells secreted type
      2 cytokines. Specific IgE was also detected in the secondary immunization, but
      due to a rapid polarization from Th2 to Th1 phenotype, exogenous IL-4 was
      required for the specific IgE secretion. Analysis of NFkappaB activation in B and
      T cells during primary and secondary immunization showed that NFkappaB could be
      detected in both B and T cells during primary immunization, but was dependent on
      exogenous IL-4 in the secondary immunization. CONCLUSION: This is the first
      evidence of antigen-specific IgE induction in vitro using naive B cells,
      demonstrating the involvement of T-helper cell phenotype and NFkappaB and
      demonstrates the usefulness of in vitro cultures to study the effect of antigens
      on human immunocytes.

PMID- 10971478
TI  - Comparative molecular modelling identifies a common putative IgE epitope on
      cysteine protease allergens of diverse sources.
AB  - BACKGROUND: Previous approaches for studying common allergenic epitopes have
      mainly focused on sequence comparisons, which unfortunately yield little or no
      information on the shape of the epitope which is the most important determinant
      of cross-reactivity. OBJECTIVES: The aim of this study was to investigate the
      structural basis for cross-reactivity between a previously identified
      immunodominant epitope of the house dust mite allergen Der p 1 (Leu147-Gln160)
      and the corresponding epitopes on other allergens that are either taxonomically
      closely related (i.e. cysteine proteases of other mite species) or representing
      evolutionary conserved structures (i.e. plant, human and parasite cysteine
      proteases). METHODS: We carried out comparative molecular modelling on a range of
      cysteine proteases, including those of other mite species (Der f 1 and Eur m 1),
      human (cathepsins B, K, L, S and O), plants (papain, chymopapain and actinidin)
      and parasites (cruzain, cathepsin L-like Leishmania protease, Entamoeba ACP1
      protease and Schistosoma Q26534, Q11003 and cathepsin L proteases). RESULTS: Our
      study shows that all the cysteine proteases investigated here display an epitope
      corresponding to that previously identified on Der p 1, but with varying shapes
      and degree of accessibility. It appears that the core of the epitope on these
      homologous cysteine proteases consists of a centrally located conserved Tyr
      residue flanked on either sides by accessible amino acids. CONCLUSION: Therefore,
      these cysteine proteases seem to use similar accessible structures, which may
      form the basis for the rational design of generic epitope-directed treatment
      strategies for controlling allergic diseases.

PMID- 10971479
TI  - Preliminary criteria for the definition of allergic rhinitis: a systematic
      evaluation of clinical parameters in a disease cohort (I).
AB  - BACKGROUND: The aim of this study is to formulate criteria for the definition of
      allergic rhinitis. Other studies have sought to develop scoring systems to
      categorize the severity of allergic rhinitis symptoms but it was never used for
      the formulation of diagnostic criteria. These other scoring systems were
      arbitrarily chosen and were not derived by any statistical analysis. To date, a
      study of this kind has not been performed. OBJECTIVE: The hypothesis of this
      study is that it is possible to formulate criteria for the definition of allergic
      rhinitis. This is the first study to systematically examine and evaluate the
      relative importance of symptoms, signs and investigative tests in allergic
      rhinitis. We sought to statistically rank, from the most to the least important,
      the multiplicity of symptoms, signs and test results. METHODS: Forty-seven
      allergic rhinitis and 23 normal subjects were evaluated with a detailed
      questionnaire and history, physical examination, serum total immunoglobulin E,
      skin prick tests and serum enzyme allergosorbent tests (EAST). RESULTS:
      Statistical ranking of variables indicated rhinitis symptoms (nasal, ocular and
      oronasal) were the most commonly occurring, followed by a history of allergen
      provocation, then serum total IgE, positive skin prick tests and positive EAST's
      to house dust mite, perennial rye and bermuda/couch grass. Throat symptoms ranked
      even lower whilst EAST's to cat epithelia, plantain and cockroach were the least
      important. Not all symptoms, signs and tests evaluated proved to be statistically
      significant when compared to a control group; this included symtoms and signs
      which had been considered historically to be traditionally associated with
      allergic rhinitis, e.g. sore throat and bleeding nose. CONCLUSION: In performing
      statistical analyses, we were able to rank from most to least important, the
      multiplicity of symptoms signs and test results. The most important symptoms and
      signs were identified for the first time, even though some of these were not
      included in our original selection criteria for defining the disease cohort i.e.
      sniffing, postnasal drip, oedematous nasal mucosa, impaired sense of smell, mouth
      breathing, itchy nose and many of the specific provocation factors.

PMID- 10971480
TI  - Corticosteroid-induced contact dermatitis: a pragmatic approach.
AB  - It is only in the past 10 years that the allergenic potential of topical
      corticosteroids has been fully realized. This has an important impact on the
      management of patients with chronic eczematous eruptions. Nonhalogenated topical
      steroids are more frequent sensitizers than halogenated molecules. Tixocortol
      pivalate and budesonide should be added to the standard series of patch test
      allergens. The topical steroid products that the patient has used should also be
      tested. If a patient has a positive reaction to tixocortol pivalate and/or
      budesonide then further patch testing with a commercial corticosteroid series
      should be undertaken.

PMID- 10971481
TI  - The use of folic acid supplementation in psoriasis patients receiving
      methotrexate: a survey in the United Kingdom.
AB  - There is little literature on the use of folic acid supplementation in psoriasis
      patients being treated with methotrexate. Under the auspices of the British
      Association of Dermatologists we surveyed, using a questionnaire, the use of
      folic acid supplementation with methotrexate therapy for psoriasis by
      dermatologists in the UK. Six-hundred and fifteen questionnaires were sent and
      153 responses were received (25%). One-hundred and fourteen of the responders
      (75%) used folic acid supplementation with methotrexate in psoriasis patients.
      Thirty (26%) of these used folic acid supplementation in all patients taking
      methotrexate and 84 (74%) used folic acid only under certain circumstances, the
      most common of which was an elevated erythrocyte mean corpuscular volume. Forty
      six per cent of respondents believed that folic acid supplementation reduced
      nausea and 60% believed that folic acid did not interfere with the efficacy of
      methotrexate. A wide variety of dosing regimens were used for folic acid
      supplementation. In the absence of guidelines and controlled trials, there is
      great variation in the indication for use, dosing regimens used and beliefs
      regarding methotrexate supplementation for psoriasis. Randomized controlled
      trials are necessary to address these questions.

PMID- 10971482
TI  - Clinical features of Ota's naevus in Koreans and its treatment with Q-switched
      alexandrite laser.
AB  - Ota's naevus is a fairly common pigmentary disorder in Asians. Recently,
      encouraging results in the treatment of Ota's naevus have been obtained, but most
      of these concerned the white skins of Caucasian patients. Our purpose was to
      examine the clinical features of Ota's naevus in Koreans and to assess the
      clinical outcomes and histological changes induced by a Q-switched alexandrite
      laser at 755 nm. Eighty-seven Koreans with Ota's naevus were studied; the peak
      age of onset was during the first decade and adolescence. The infraorbital area
      was the most frequent site and black or dark brown colours predominated.
      Improvements were achieved in 52 patients (77%). Better results were obtained in
      unilateral lesions and patients who received a greater number of treatments. Mild
      hyperpigmentation after treatment was noticed in 14 patients and mild
      hypopigmentation in eight patients. However, all of these were reversed in time.
      Hypertrophic scarring or secondary infection did not occur. The histology of
      laser-irradiated lesions showed selective thermal damage of melanocytes in the
      upper dermis and the elimination of upper dermal pigmentation. Our clinical data
      demonstrate the usefulness of the Q-switched alexandrite laser for the treatment
      of Ota's naevus in brown skin.

PMID- 10971483
TI  - Granuloma annulare following waxing induced pseudofolliculitis-resolution with
      isotretinoin.
AB  - We report a case of localized granuloma annulare, successfully treated with
      isotretinoin, which occurred as a consequence of waxing-induced
      pseudofolliculitis. To our knowledge this is the first reported clearance of
      localized granuloma annulare with isotretinoin and the first reported case of
      granuloma annulare as a sequel to pseudofolliculitis.

PMID- 10971484
TI  - Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis.
AB  - We report a 32-year-old man who presented with a 2-year history of unexplained
      weight loss and symptoms of Raynaud's phenomenon. Clinical examination and
      investigations were consistent with a diagnosis of acquired partial lipodystrophy
      (Barraquer-Simons disease). This patient also exhibited an associated cutaneous
      vasculitis and peripheral perniotic changes. He had normal renal function and
      glucose tolerance and no immunological abnormality has been detected in his serum
      to date. The absence of C3-nephritic factor in the presence of overt
      lipodystrophy suggests that there may be another factor or immunological mediator
      responsible for the subcutaneous changes seen in patients with lipodystrophy.

PMID- 10971485
TI  - Schnitzler's syndrome: no evidence for autoimmune basis in two patients.
AB  - We report two cases of Schnitzler's syndrome in which anti-interleukin-1alpha
      autoantibodies and functional autoantibodies against the high affinity IgE
      receptor (FcepsilonRIalpha) or against IgE were absent. One patient responded
      well to TL-01 phototherapy, a treatment which may be considered in patients with
      Schnitzler's syndrome if, as is usually the case, they are unresponsive to
      antihistamine therapy.

PMID- 10971486
TI  - Equestrian perniosis associated with cold agglutinins: a novel finding.
AB  - Reports of equestrian perniosis are rare in the literature and in the cases
      previously described there have been no abnormal laboratory investigations. We
      describe two patients with equestrian perniosis who had persistently elevated
      titres of cold agglutinins. We discuss the relationship of these cold agglutinins
      to the pathogenesis of perniosis and other related skin disorders.

PMID- 10971487
TI  - Discrete papular mucinosis-a rare subtype of lichen myxoedematosus.
AB  - Lichen myxoedematosus is an uncommon and distinct disease entity characterized by
      cutaneous mucin deposition which, depending on the distribution and overall skin
      involvement, can be classified into several subtypes. We now describe the case of
      a discrete papular type of lichen myxoedematosus in a patient without any
      conspicious laboratory findings including normal thyroid function and the absence
      of any abnormal immunglobulins.

PMID- 10971488
TI  - Papuloerythroderma of Ofuji responding to treatment with cyclosporin.
AB  - We describe a patient with papuloerythroderma of Ofuji (PE) of unknown cause, in
      whom no underlying malignancy was found. Topical steroids and systemic
      antihistamines did not resolve the rash. Systemic steroids induced a remission of
      the PE, which was not maintained on reduction of the dose. Therefore, cyclosporin
      was added which did lead to rapid clearing of the skin. Remission was maintained
      after discontinuation of treatment.

PMID- 10971489
TI  - Sweet's syndrome and polycythaemia rubra vera.
AB  - Sweet's syndrome is associated with haematological malignancy, particularly acute
      myelogenous leukaemia, but there are few reports of its association with
      polycythaemia rubra vera. We describe an 85-year-old man with polycythaemia rubra
      vera who developed Sweet's syndrome and review the literature of this
      association.

PMID- 10971490
TI  - Acne fulminans 'sine fulminans'.
AB  - Acne fulminans is characterized by the sudden onset of a severe, ulcerative acne
      associated with systemic features. Response to traditional acne therapies is
      poor. We have recognized a subset of patients with acne of a severity comparable
      to that of acne fulminans but with the absence of systemic involvement; we
      suggest modification of the treatment regimes used in this group.

PMID- 10971491
TI  - Squamous cell carcinoma arising in transplanted skin.
AB  - Squamous cell carcinoma arising in a skin graft is rare. Previous reports concern
      the use of skin in heterotopic locations namely the vagina and oral cavity. We
      report a case of squamous cell carcinoma, which arose in a skin graft used for
      resurfacing a scalp defect. The defect followed the excision of a basal cell
      carcinoma 11 years previously. The excision was incomplete and radiotherapy had
      been given. The possible pathological mechanisms for the development of a
      squamous cell carcinoma in transplanted skin are discussed.

PMID- 10971492
TI  - Alkaptonuric ochronosis presenting as palmoplantar pigmentation.
AB  - We describe a 37-year-old woman who presented with palmoplantar pigmentation,
      thickening and pitting of 4 years duration. Bluish pigmented patches were seen
      over the sclera of her eyes. Her lumbar spine showed typical calcification of the
      intervertebral discs. Addition of Benedict's reagent to a urine sample of the
      patient gave rise to greenish brown precipitate and brownish black supernatant.
      Alkalinization of urine turned it black. A biopsy of the palmar lesion
      demonstrated irregular breaking up, swelling and homogenization of collagen
      bundles in the reticular dermis. Yellow-brown (ochre coloured) pigment was seen
      lying within the collagen bundles and also freely in the deeper dermis confirming
      our clinical diagnosis of alkaptonuric ochronosis. To the best of our knowledge
      this is probably the second report of alkaptonuria presenting with palmoplantar
      pigmentation.

PMID- 10971493
TI  - Poland's syndrome and recessive X-linked ichthyosis in two brothers.
AB  - Poland's syndrome consists of unilateral congenital absence of the pectoralis
      major muscle with a variable degree of ipsilateral upper limb deformity. The
      aetiology of Poland's syndrome is unknown, although an inherited tendency to
      develop a compromised embryonic vascular supply in the affected areas has been
      suggested. The majority of reported cases are sporadic, and in only a few
      instances is there a familial incidence. We describe the occurrence of Poland's
      syndrome in two brothers who also had recessive X-linked ichthyosis. To the best
      of our knowledge this is the first report of such an association.

PMID- 10971494
TI  - Detection of antigen-specific cytotoxic T lymphocytes: significance for
      investigative dermatology.
AB  - Novel recombinant tetrameric complexes of HLA class I molecules allow the direct
      visualization of antigen-specific CD8+ T cells using flow cytometry. By
      facilitating the quantification, isolation and phenotypic analysis of CD8+ T
      cells, the use of HLA tetramers has extended our understanding of the role of
      cellular immunity in various disease settings. Recently the technique has also
      been applied to the study of cutaneous disease and provides insights into
      mechanisms of dermatopathology.

PMID- 10971495
TI  - Delta-aminolevulinic acid in superficial basal cell carcinomas and normal skin-a
      microdialysis and perfusion study.
AB  - Delta-aminolevulinic acid (ALA) is used for photodynamic therapy of basal cell
      carcinoma (BCC) as it is converted to protoporphyrin IX in tumour tissue. During
      illumination with 635 nm light a photochemical reaction takes place, singlet
      oxygen is generated and the tumour destroyed. In this study we used the
      microdialysis technique to quantify the concentration of ALA at a certain depth
      in tumour and healthy skin. The penetration ability of ALA was investigated as a
      function of time in BCCs (n = 14) and in normal skin (n = 4) after topical
      application. The microdialysis catheters were inserted intracutaneously and the
      depth position recorded by means of ultrasound. Microdialysate sample
      concentrations of amino acids and ALA were determined by high performance ion
      exchange chromatography. A laser Doppler perfusion imager measured perfusion in
      the BCCs. The data show that the average depth of the microdialysis catheters was
      0.5 mm. The interstitial ALA concentration in the BCCs increased from 0 to 3.1
      mmol/L 15 min after application of ALA, whereas no measurable amounts of ALA were
      found in healthy skin. The blood perfusion was 2.5-fold increased in the BCCs.
      The interstitial levels of amino acids were not significantly changed during the
      ALA treatment. In summary, we found that ALA rapidly penetrates tumour skin. We
      conclude that microdialysis seems to be well suited for pharmacodynamic studies
      of ALA in skin.

PMID- 10971496
TI  - Simple horizontal averaging programme enables shade correction for image analysis
      in psoriasis.
AB  - Computer-assisted area measurement of skin lesions would be useful for the
      assessment of disease severity. Difficulties can be encountered, however, when
      lesions cannot simply be separated using the normal threshold tool of an image
      analyser. Owing to body curvature, peripheral sites are usually shadowed. To
      obtain a well-fitting curved line to account for body curvature-induced glare and
      shadow, we devised a simple C-programme for averaging neighbouring pixels on the
      same horizontal line. An image was captured from a colour slide to the image
      analysis system. C++ was used for programming. Execution of the averaging
      programme with the original image resulted in a background brightness image file.
      When this was subtracted from the original image, the lesions were easily
      detected using the standard threshold tool and the percentage of area involved
      was calculated. This method is sufficiently accurate for the assessment of
      disease severity.

PMID- 10971498
TI  - Recent advances in urticaria angioedema and related disorders, 8-9 april 1999

PMID- 10971497
TI  - Observations on high levels of fusidic acid resistant Staphylococcus aureus in
      Harrogate, North Yorkshire, UK.
AB  - A retrospective study was carried out to investigate possible reasons for a
      marked increase in fusidic acid-resistant Staphylococcus aureus (FusR S. aureus)
      identified by our routine hospital microbiology service. Information was obtained
      on a sample of 64 consecutive patients from whom resistant S. aureus had been
      cultured. The source of isolates was found to be diffuse within the hospital and
      community. The site of sample was most frequently chronic cutaneous infections
      (68%). All the S. aureus isolates were resistant to both fusidic acid and
      penicillin and many were resistant to multiple antibiotics. Topical fusidic acid
      had been used by 40% of patients in the preceding 6 months and none had received
      oral fusidic acid (sodium fusidate). Most (80%) had received an oral antibiotic
      in the preceding 2 years. Information from the Prescriptions Pricing Authority
      revealed that the total number of prescriptions for fusidic acid-containing
      preparations for the period September 1997 to August 1998 was markedly higher in
      Harrogate than in five other local areas where increases in (FusR) S. aureus have
      not been observed.

PMID- 10971499
TI  - Scalp ringworm epidemic in Birmingham: a decline?

PMID- 10971500
TI  - Prolonged toxic epidermal necrolysis due to Lamotrigine.

PMID- 10971501
TI  - Cryotherapy may be effective for eyelid xanthelasma.

PMID- 10971502
TI  - Exacerbation of psoriasis by interferon-alpha therapy for hepatitis C.

PMID- 10971503
TI  - Iritis associated with Sweet's syndrome.

PMID- 10971504
TI  - Perianal subcutaneous abscess caused by Streptococcus intermedius in a patient
      with multicentric Castleman's disease.

PMID- 10971505
TI  - Clinical consequences of defects in the IL-12-dependent interferon-gamma (IFN
      gamma) pathway.

PMID- 10971506
TI  - Angiogenesis in inflammatory joint disease: a target for therapeutic
      intervention.

PMID- 10971507
TI  - Probing the human natural autoantibody repertoire using an immunoscreening
      approach.
AB  - While an increasing number of studies report the presence of antibodies capable
      of recognizing self-antigens, the function of these natural autoantibodies
      remains elusive. A variety of concepts has been advanced ranging from
      evolutionarily tolerated but non-functional natural autoantibodies to
      autoantibodies effecting various biological functions. Known IgM, IgG, and IgA
      natural autoantibodies are directed against various antigens, including nuclear
      and cell surface proteins. To explore further autoantibodies and their
      autoantigens, we employed an immunological screening method called SEREX recently
      used to characterize tumour-expressed antigens eliciting an immune response in
      patients [1]. Sera from 12 individuals were used to screen a cDNA expression
      library prepared from a cytogenetically normal meningioma to identify antigens
      reactive with normal human sera from individuals without obvious disease.
      Nineteen reactive normal antigen clones were identified representing 15 different
      antigens, including nine genes with known functions, five genes with unknown
      functions, and one gene with a novel sequence not present in the databases. Of
      the 12 individual normal sera tested, 75% were reactive to one or more of the 15
      different antigens with two highly reactive sera demonstrating reactivity with
      33% of the antigens. When screening the same meningioma expression library with
      serum from the patient, eight antigens were identified that were totally
      different from those identified using sera from normal individuals. This SEREX
      immunological screening method presents a new option for probing the natural
      autoantibody repertoire and identifying normal antigens whose functions may
      provide additional insights into how natural autoantibodies effect various
      biological functions.

PMID- 10971509
TI  - Distribution of age-related thymulin titres in normal subjects through the course
      of life.
AB  - The thymus has a dominant immunological role in utero and in early childhood,
      being a primary source of T lymphopoiesis, and its investigation may be
      particularly relevant for the immunological study of paediatric patients.
      Thymulin, a nonapeptide secreted by the thymus, is an essential hormone for T
      lymphocyte differentiation and function. As thymulin values in the normal
      population have not been well documented, especially for children under the age
      of 1 year, we detail thymic endocrine function by presenting age-related plasma
      thymulin levels in a large series (n = 93) of healthy individuals, ranging from
      birth to old age. We demonstrate that thymulin is already detectable at birth; it
      then gradually increases with age, reaching the highest level in children aged 5
      10 years. Starting at adolescence, thymulin titres gradually start to fall,
      reaching the lowest value at 36 years of age and remaining steady until 80 years
      (the oldest person tested).

PMID- 10971508
TI  - Significance of chemokines and activated platelets in patients with diabetes.
AB  - Levels of platelet-derived microparticles (PMPs), platelet activation markers (P
      selectin expressed on, or annexin V binding to, platelets (plt:P-selectin or
      plt:annexin V, respectively)), chemokines (IL-8, monocyte chemotactic peptide-1
      (MCP-1), and regulated on activation normally T-cell expressed and secreted
      (RANTES)), and soluble P- and E-selectins were compared in peripheral blood from
      diabetic and control patients in order to develop a better understanding of their
      potential contribution to diabetic vascular complications. Significant increases
      were found for PMPs, plt:P-selectin, MCP-1, RANTES and soluble P- and E-selectins
      in diabetic individuals, whereas IL-8 levels were similar. Furthermore, after
      ticlopidine treatment, most of these factors receded to baseline levels observed
      in non-diabetic patients. Our findings indicate that ticlopidine might be able to
      prevent or reduce vascular complications in diabetic patients.

PMID- 10971510
TI  - Both Th1- and Th2-derived cytokines in serum are elevated in Graves'
      ophthalmopathy.
AB  - Increased serum cytokine levels have been reported in patients with autoimmune
      thyroid disease, but less is known about their levels in patients with Graves'
      ophthalmopathy (GO). It is not known whether GO is a cell-mediated or humoral
      autoimmune disease. We investigated whether serum cytokines are elevated in GO
      patients and whether the cytokines were Th1- or Th2-derived. In addition,
      elevated cytokines might reflect the activity of GO, and thus we investigated
      whether cytokine levels could predict the clinical response to orbital
      radiotherapy. We studied 62 consecutive patients with moderately severe untreated
      GO and 62 healthy controls, matched for sex, age and smoking habits. Serum
      concentrations of IL-1RA, sIL-2R, IL-6, sIL-6R, tumour necrosis factor-alpha (TNF
      alpha) RI and II and sCD30 were measured using highly sensitive ELISAs, in the
      patients before and 3 and 6 months after radiotherapy. All patients were
      euthyroid, with anti-thyroid drugs, before and during the entire study period.
      All baseline cytokine and cytokine receptor levels were significantly elevated in
      GO patients compared with healthy controls, except for IL-1RA. The levels did not
      correlate with parameters of the thyroid disease, nor with the duration, activity
      or severity of GO. However, backward logistic regression analysis showed that IL
      6, sCD30 and TNFalphaRI were able to predict a beneficial response to orbital
      radiotherapy. We therefore conclude that both Th1- and Th2-derived cytokines are
      elevated in GO patients compared with its controls. IL-6, sCD30 and TNFalphaRI
      had some value for predicting therapeutic outcome to orbital irradiation, and may
      thus reflect active eye disease.

PMID- 10971511
TI  - Triamcinolone acetonide modulates permeability and intercellular adhesion
      molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular
      degeneration.
AB  - Whilst animal studies and a pilot clinical trial suggest that intravitreal
      triamcinolone acetonide (TA) may be useful in the treatment of age-related
      macular degeneration (AMD), its mode of action remains to be fully elucidated.
      The present study has investigated the capacity of TA to modulate the expression
      of adhesion molecules and permeability using a human epithelial cell line
      (ECV304) as a model of the outer blood-retinal barrier (BRB). The influence of TA
      on the expression of ICAM-1 and MHC-I was studied on resting and phorbol
      myristate acetate (PMA)- or interferon-gamma (IFN-gamma)- and/or tumour necrosis
      factor-alpha (TNF-alpha)-activated cells using flow cytometry and
      immunocytochemistry. Additionally, ECV304 cells were grown to confluence in
      uncoated Transwell chambers; transepithelial resistance (TER) across resting and
      PMA-activated cells was monitored. TA significantly decreased the paracellular
      permeability of ECV304 cells and down-regulated ICAM-1 expression, consistent
      with immunocytochemical observations. PMA-induced permeability changes were dose
      dependent and TA decreased permeability of both resting and PMA-activated
      monolayers. MHC-I expression by ECV304 cells however, was not significantly
      affected by TA treatment. The modulation of TER and ICAM-1 expression in vitro
      correlate with clinical observations, suggesting re-establishment of the BRB and
      down-regulation of inflammatory markers are the principal effects of intravitreal
      TA in vivo. The results further indicate that TA has the potential to influence
      cellular permeability, including the barrier function of the retinal pigment
      epithelium (RPE) in AMD-affected retinae.

PMID- 10971512
TI  - Autoimmunity in ulcerative colitis (UC): a predominant colonic mucosal B cell
      response against human tropomyosin isoform 5.
AB  - We set out to examine if the IgG-producing cells in the colonic mucosa in UC are
      committed to tropomyosin isoform 5 (hTM5), a putative autoantigen in UC. Lamina
      propria mononuclear cells (LPMC) were isolated from colonoscopic biopsy specimens
      from recto-sigmoid and proximal colon. Twenty-three patients with UC, eight with
      Crohn's colitis (CC), and 10 non-inflammatory bowel disease (non-IBD) controls
      were included. The ELISPOT assays were used to quantify lamina propria B cells
      producing total immunoglobulin (IgA, IgG, IgM), IgG, IgA, as well as IgG against
      hTM5 isoform. The median value of percentage of total IgG-producing lymphocytes
      was similar in UC (12%) and CC (11%), but was significantly (P < 0.0002) higher
      than non-IBD controls (6%). However, in UC, but not in CC and non-IBD, a large
      number of lamina propria B cells produced IgG against hTM5 (median values: UC
      42%, CC 2.5%, non-IBD 0%). This difference in UC when compared with CC and non
      IBD was highly significant (P < 0.00001). Twenty-one of 23 (91%) patients with UC
      had percentage of anti-hTM5 IgG-producing immunocytes more than 2 s. d. above the
      mean for non-UC patients. In UC but not in CC and non-IBD controls, the increased
      number of IgG-producing cells are largely committed to produce IgG against hTM5
      related epitope(s).

PMID- 10971513
TI  - Thalidomide analogue CC-3052 reduces HIV+ neutrophil apoptosis in vitro.
AB  - Thalidomide has significant immunomodulatory properties and has been used
      successfully in the treatment of oral ulcers and wasting in HIV patients.
      However, its use is limited by its poor bioavailability due to low solubility and
      short half life in solution, and teratogenic and neurotoxic side-effects.
      Recently, water-soluble analogues of thalidomide with significantly greater
      immunomodulatory activity and reduced side-effects have become available. We
      examined the effect of thalidomide and one analogue, CC-3052, on neutrophil
      apoptosis following culture for 20 h in vitro. Apoptosis was assessed by reduced
      CD16 expression and Annexin V binding using flow cytometry. Thalidomide or CC
      3052 alone had no effect on neutrophil apoptosis when used at physiological
      levels. However, when used together with prostaglandin E2 (10-7 M), a potent
      adenylate cyclase activator, CC-3052 but not thalidomide (both 10-5 M) reduced
      apoptosis in neutrophils from normal and HIV+ donors. The reduced apoptosis could
      not be attributed to the ability of CC-3052 to reduce tumour necrosis factor
      alpha (TNF-alpha) production, but may be due to its PDE4 inhibitor properties, as
      it increased [cAMP]i, and mimicked the effect of increasing [cAMP]i using
      dibutryl cAMP, a membrane-permeable analogue of cAMP. The results suggest a role
      for thalidomide analogue CC-3052 in reducing persistent activation of the TNF
      alpha system in HIV without markedly impairing neutrophil viability.

PMID- 10971515
TI  - Resistance/susceptibility to Echinococcus multilocularis infection and cytokine
      profile in humans. I. Comparison of patients with progressive and abortive
      lesions.
AB  - To clarify the role of Th1- and Th2-type cytokines in the various outcomes of
      human alveolar echinococcosis (AE), the cytokine immune response of self-cured
      patients was studied and compared with those of progressive AE patients and
      healthy subjects. Self-cured patients were divided into two groups according to
      the following clinical features: subjects who had positive Echinococcus
      multilocularis serologies and hepatic calcifications typical of AE were
      classified as 'abortive AE' patients, and those who had positive E.
      multilocularis serologies but no hepatic lesions or calcifications detectable by
      ultrasonography were classified as 'positive serology' subjects. Secretions of IL
      5, IL-10 and interferon-gamma, and expression of IL-5 mRNA were evaluated in
      peripheral blood mononuclear cells (PBMC) stimulated in vitro with the mitogen
      phytohaemagglutinin-C or specific E. multilocularis antigenic preparations. The
      cytokine profile of abortive AE patients was the opposite of that observed in
      progressive AE patients. An intermediate profile was observed in positive
      serology subjects. PBMC from abortive AE patients, whether non-stimulated or
      stimulated with PHA and antigenic preparations, secreted significantly lower
      levels of IL-10 than those isolated from progressive AE patients. Our
      observations seem to confirm the regulatory role of IL-10 in the immunopathology
      of human AE.

PMID- 10971514
TI  - TNFA promoter polymorphism and susceptibility to brucellosis.
AB  - The aim of this study was to investigate the possible influence of the tumor
      necrosis factor alpha (TNFA) gene promoter polymorphisms and HLA class II genes
      on the susceptibility to or development of human brucellosis. TNFA genotypes (at
      positions -308 and -238) were determined in 59 patients with brucellosis and 160
      healthy controls by polymerase chain reaction-restriction fragment length
      polymorphism. There were no significant differences between the patients and the
      controls for the TNFA-238 genotypes. However, when the overall TNFA-308 genotype
      distribution of the brucella patients was compared with that of the control
      subjects, a significant skewing was observed (P = 0.02). The TNFA-308.1/2
      genotype was present at significantly higher frequency in the total patient as a
      whole compared with control subjects (30% versus 15%; P = 0.01, odds ratio (OR)
      2.49, 95% confidence interval (CI) 1.16-5.33). No statistically significant
      differences in the distribution of HLA-DRB1 or DQB1 alleles were observed between
      brucella patients and control subjects. Stratification to correct for
      interdependence of TNFA-308.2 and HLA-DR3 alleles confirmed that, in spite of
      their strong linkage disequilibrium, the association of TNFA-308.2 with
      brucellosis was independent of HLA-DR3.

PMID- 10971516
TI  - Resistance/susceptibility to Echinococcus multilocularis infection and cytokine
      profile in humans. II. Influence of the HLA B8, DR3, DQ2 haplotype.
AB  - Differences have been shown between HLA characteristics of patients with
      different courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, DQ2
      haplotype was associated with more severe forms of this granulomatous parasitic
      disease. We compared IL-10, IL-5, interferon-gamma (IFN-gamma) and tumour
      necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC)
      isolated from eight HLA-DR3+, DQ2+, B8+ AE patients and from 10 HLA-DR3-, DQ2-,
      B8- patients after non-specific mitogenic and specific Echinococcus
      multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3+, DQ2+,
      B8+ healthy subjects and nine HLA-DR3-, DQ2-, B8- subjects were also studied as
      controls. PBMC from AE patients with HLA DR3+, DQ2+ haplotype secreted higher
      levels of IL-10 without any stimulation and after specific antigenic stimulation
      than did patients without this haplotype. Higher levels of IL-5 and IFN-gamma
      were also produced by these patients' PBMC after stimulation with non-purified
      parasitic antigenic preparations; however, the specific alkaline phosphatase
      antigen extracted from E. multilocularis induced only Th2-type cytokine
      secretion. A spontaneous secretion of TNF by HLA DR3+, DQ2+ B8+ AE patients was
      also found. These results suggest that HLA characteristics of the host can
      influence immune-mediated mechanisms, and thus the course of AE in humans;
      specific antigenic components of E. multilocularis could contribute to the
      preferential Th2-type cytokine production favoured by the genetic background of
      the host.

PMID- 10971517
TI  - Enhancement of natural killer (NK) cell cytotoxicity and induction of NK cell
      derived interferon-gamma (IFN-gamma) display different kinetics during
      experimental infection with Trypanosoma cruzi.
AB  - Early immunological activation involves an initial phase of cytokine activity and
      involvement of cell types such as NK cells. Such early immune responses are often
      decisive in resolution of microbial infection. NK cells reduce parasitaemia and
      enhance survival in experimental Trypanosoma cruzi infection, although the nature
      of these protective effects is not well understood. In this study, a detailed
      analysis of innate cytokine induction in the absence and presence of NK cells
      during the first 8 days of infection was performed. Following intraperitoneal
      infection with a high dose of parasites, reverse transcriptase-polymerase chain
      reaction showed that splenic mRNA for IFN-gamma appeared as a peak 24 h after
      infection and then reappeared 2-3 days later. In NK-depleted animals the first
      peak of IFN-gamma was absent and the second wave was slightly delayed. mRNA for
      IL-12 and tumour necrosis factor-alpha (TNF-alpha) as well as IFN-alpha protein
      in serum was only recorded 24 h after infection, at the same time as the IFN
      gamma peak. NK depletion resulted in a small decrease of IL-12 mRNA levels,
      whereas TNF-alpha and IFN-alpha were not affected. NK cytotoxicity remained
      elevated throughout the 8 days and thus did not parallel the expression of IFN
      gamma production by NK cells. We conclude that NK cell cytokine production and
      cytolytic activity play different roles in response to challenge with T. cruzi.

PMID- 10971518
TI  - Deficiency in circulating natural killer (NK) cell subsets in common variable
      immunodeficiency and X-linked agammaglobulinaemia.
AB  - Absolute and relative NK cell numbers were determined in peripheral whole blood
      by flow cytometry in patients with common variable immunodeficiency (CVID) (n =
      55) and X-linked agammaglobulinaemia (XLA) (n = 19) on regular immunoglobulin
      (IVIG) therapy. Absolute CD3-CD16+ NK cell numbers were significantly reduced in
      CVID patients (median 108/microl, range 23-815), compared with normal subjects (n
      = 60) (289/microl, range 56-640, P < 0.001). Total lymphocyte concentrations were
      significantly lower in CVID (median 1587/microl, range 523-7519) compared with
      normal subjects (median 2019/microl, range 1124-3149, P = 0.004), with the
      percentage of NK cells also being significantly decreased (median 7.5%, range 3.0
      33. 0%, compared with 14.2%, range 2.6-30.8%, P < 0.001). In XLA, absolute NK
      cell numbers (median 140/microl, range 32-551, P < 0. 001) but not relative
      numbers were significantly reduced compared with normal controls. We excluded the
      possibility that IVIG interferes with in vitro binding of CD16 MoAbs. Further
      analysis of NK cell subsets showed a deficiency of both CD16+ and CD56+ cells in
      CVID, most marked in the CD3-CD8dim subpopulation, which may be due to increased
      homing of these cells to the gut. Serial studies on a small number of patients
      suggest that IVIG therapy has no short-term effect on NK cells, although we
      cannot exclude an effect with prolonged use. Although there are no obvious
      clinical effects of the NK depletion in CVID and XLA, this may be a factor in
      their predisposition to cancer.

PMID- 10971520
TI  - Up-regulation of the tumour-associated marker CD44V6 in experimental kidney
      disease.
AB  - CD44 is an adhesion molecule involved in a wide range of cell-cell and cell
      matrix interactions. The standard form of CD44 (CD44S) is a 85-90-kD
      glycoprotein, but alternative splicing of RNA encoding 10 variable exons (V1-V10)
      can give rise to many different CD44 variant protein isoforms of higher molecular
      weight. CD44 isoforms containing the V6 exon play a crucial role in tumour
      metastasis and lymphocyte activation. However, the role of CD44V6 in the kidney
      is unknown. The aim of this study was to examined renal CD44V6 expression in
      health, disease and in vitro. Immunohistochemistry staining with the V6-specific
      1.1ASML antibody identified constitutive CD44V6 expression by occasional cortical
      tubular epithelial cells and medullary tubules in normal rat kidney. In immune
      induced kidney disease (rat anti-glomerular basement membrane
      glomerulonephritis), there was a marked increase in CD44V6 expression by cortical
      tubules, particularly in areas of tubulointerstitial damage, which was associated
      with focal macrophage infiltration. There was also a marked increase in CD44V6
      expression by damaged tubules in a model of non-immune kidney disease (unilateral
      ureteric obstruction). Reverse transcription-polymerase chain reaction revealed a
      complex pattern of CD44V6-containing mRNA isoforms in normal rat kidney. This
      pattern of CD44V6 splicing was essentially unaltered in disease. The NRK52E
      normal rat kidney tubular epithelial cell line expresses both CD44S and CD44V6.
      Stimulation of NRK52E cells with IL-1 or transforming growth factor-beta 1
      induced a two-to-five-fold increase in the expression of both CD44S and CD44V6.
      Furthermore, triggering of NRK52E cells by antibodies to CD44S or CD44V6, but not
      isotype control antibodies, induced secretion of monocyte chemoattractant protein
      1. In conclusion, this study has identified expression of the tumour-associated
      marker CD44V6 in tubular epithelial cells in normal and diseased rat kidney, and
      suggests that signalling through the CD44V6 molecule may participate in the
      pathogenesis of experimental kidney disease.

PMID- 10971519
TI  - Angiotensin-converting enzyme inhibitor captopril prevents activation-induced
      apoptosis by interfering with T cell activation signals.
AB  - Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE)
      which is widely used as an anti-hypertensive agent. In addition to its ability to
      reduce blood pressure, captopril has a number of other biological activities.
      Recently the drug was shown to inhibit Fas-induced apoptosis in human activated
      peripheral T cells and human lung epithelial cells. In this study, we
      investigated whether captopril blocks activation-induced apoptosis in murine T
      cell hybridomas, and found that captopril inhibited IL-2 synthesis and apoptotic
      cell death upon activation with anti-CD3 antibody. In addition, captopril
      inhibited an inducible caspase-3-like activity during activation-induced
      apoptosis. On the other hand, captopril did not interfere with Fas signalling,
      since anti-Fas antibody-induced apoptosis in Fas+ Jurkat cells was unaffected by
      the drug. Furthermore, we examined whether captopril blocks activation-induced
      apoptosis by interfering with expression of Fas, Fas ligand (FasL), or both on T
      cell hybridomas. FasL expression on activated T cells was significantly inhibited
      by captopril, whereas up-expression of Fas was partially inhibited, as assessed
      by cell surface staining. Taking all data together, we conclude that captopril
      prevents activation-induced apoptosis in T cell hybridomas by interfering with T
      cell activation signals. Captopril has been reported to induce systemic lupus
      erythematosus syndrome, and our findings may be useful for elucidating the
      mechanism of captopril-induced autoimmunity.

PMID- 10971522
TI  - Anti-topoisomerase II alpha autoantibodies in systemic sclerosis-association with
      pulmonary hypertension and HLA-B35.
AB  - We have previously detected autoantibodies against topoisomerase II alpha (anti
      topo II alpha) in sera from patients with idiopathic pulmonary fibrosis. To
      determine whether anti-topo II alpha is also present in systemic sclerosis (SSc)
      patients with pulmonary involvement, we screened sera from 92 patients and 34
      healthy controls. Presence of anti-topo II alpha was investigated with respect to
      clinical and serological features, including the frequencies of HLA class I and
      II alleles. Anti-topo II alpha was detected in 20/92 (21.7%) patients. No
      association was found with either anti-topoisomerase I (Scl-70 or anti-topo I) or
      anti-centromere antibodies. However, anti-topo II alpha was associated with the
      presence of pulmonary hypertension (PHT) (as opposed to pulmonary fibrosis), and
      with a decrease of carbon monoxide diffusing capacity. Anti-topo II alpha was
      strongly associated with the presence of the class I antigen HLA-B35. No
      significant association was found with HLA class II antigens. HLA-B35 also turned
      out to be associated with the presence of PHT. These results indicate that in SSc
      patients, the presence of anti-topo II alpha is associated with PHT, and that the
      simultaneous presence of HLA-B35 seems to add to the risk of developing PHT.

PMID- 10971521
TI  - Expression of vascular endothelial growth factor by synovial fluid neutrophils in
      rheumatoid arthritis (RA).
AB  - Most of the leucocytes infiltrating rheumatoid synovial fluid (SF) are
      neutrophils capable of producing a variety of inflammatory mediators known to
      contribute significantly to the disease process during active RA. In the present
      study, we investigated the contribution made by SF neutrophils to the elevated
      levels of vascular endothelial growth factor (VEGF) seen in rheumatoid SF.
      Rheumatoid SF neutrophils were found to contain significantly larger amounts of
      both VEGF protein and its mRNA than peripheral blood neutrophils from either RA
      patients or healthy controls. Levels of cell-associated VEGF were well correlated
      with free VEGF in SF, which was significantly higher than in SF from
      osteoarthritis patients. Levels of SF neutrophil-associated VEGF also correlated
      with RA disease activity and cell surface integrin expression. Thus, SF
      neutrophil-associated VEGF may be considered an indicator of both local and
      systemic inflammation of RA, contributing to the neovascularization seen during
      RA synovitis.

PMID- 10971523
TI  - False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody
      complexes: a source for analytical error in serologic evaluation of anti
      neutrophil cytoplasmic autoantibodies.
AB  - Anti-myeloperoxidase antibodies (anti-MPO) are a major type of anti-neutrophil
      cytoplasmic antibody (ANCA). While evaluating anti-MPO monoclonal antibodies from
      SCG/Kj mice, we observed several hybridomas that appeared to react with both MPO
      and DNA. Sera from some patients with systemic lupus erythematosus (SLE) also
      react with MPO and DNA. We hypothesized that the MPO binding activity is a false
      positive result due to the binding of DNA, contained within the antigen binding
      site of anti-DNA antibodies, to the cationic MPO. Antibodies from tissue culture
      supernatants from 'dual reactive' hybridomas were purified under high-salt
      conditions (3 M NaCl) to remove any antigen bound to antibody. The MPO and DNA
      binding activity were measured by ELISA. The MPO binding activity was completely
      abrogated while the DNA binding activity remained. The MPO binding activity was
      restored, in a dose-dependent manner, by the addition of increasing amount of
      calf-thymus DNA (CT-DNA) to the purified antibody. Sera from six patients with
      SLE that reacted with both MPO and DNA were treated with DNase and showed a
      decrease in MPO binding activity compared with untreated samples. MPO binding
      activity was observed when CT-DNA was added to sera from SLE patients that
      initially reacted with DNA but not with MPO. These results suggest that the DNA
      contained within the antigen binding site of anti-DNA antibodies could bind to
      the highly cationic MPO used as substrate antigen in immunoassays, resulting in a
      false-positive test.

PMID- 10971524
TI  - Study of antibody and T cell responses in rabbits immunized with synthetic human
      B cell epitope analogues of La (SSB) autoantigen.
AB  - The aim of this study was to investigate the immunogenicity of four synthetic
      peptides, representing linear B cell epitopes of the human La/SSB autoantigen:
      145-164 aa (p1), 289-308 aa (p2), 301-318 aa (p3) and 349-364 aa (p4), in
      rabbits. New Zealand White rabbits were immunized with each of the above peptides
      attached in four copies on tetrameric sequential oligopeptide carriers (SOC) in
      duplicate. Control immunizations were also performed (one rabbit each, immunized
      with Freud's complete adjuvant alone or with the SOC carrier alone). Animals were
      bled at regular intervals and sera were analysed for anti-La/SSB activity by
      ELISA assays using as antigen the various synthetic peptides, as well as the
      whole La/SSB protein. Four months after the last immunization, the animals were
      killed and peripheral blood mononuclear and spleen cells were co-cultured with
      either the peptides, the SOC carrier, or 27 peptides, covering the entire length
      of the human La/SSB molecule (23 amino acids long, overlapping by eight residues
      to each other). A specific, IgG, anti-peptide antibody response was detected,
      initially directed against the priming peptide, and subsequently expanded to the
      other La/SSB synthetic peptides. The antibody titres remained high, even 4 months
      after the last immunization. Sera from rabbits immunized with either p2 or p3
      reacted also with the whole La/SSB protein, as was demonstrated by ELISA and
      immunoblot assays. No reactivities against either Ro60 or Ro52 autoantigen were
      found. Rabbit spleen cell reacted not only with the epitope used for the
      immunization but also with other La/SSB peptides. Immunization of rabbits with
      the major human La/SSB B cell antigenic determinants, linked to SOC carrier,
      induces strong and sustained antibody and T cell responses against multiple
      epitopes of the human La/SSB protein. Thus, La/SSB B cell linear epitopes are
      probably capable also of functioning as T cell epitopes, in this experimental
      animal.

PMID- 10971525
TI  - Islet xenograft destruction in the hu-PBL-severe combined immunodeficient (SCID)
      mouse necessitates anti-CD3 preactivation of human immune cells.
AB  - Introduction of the hu-PBL-SCID mouse model has yielded a potentially useful tool
      for research in transplantation. The aim of this study was to define the
      conditions necessary for a reconstituted human immune system to destroy in a
      consistent manner rat islet xenografts in the alloxan-diabetic hu-PBL-SCID mouse.
      We examined different time points of hu-PBL reconstitution, different
      transplantation sites of the islets and several hu-PBL reconstitution protocols.
      Major differences in graft destruction were observed between the different hu-PBL
      reconstitution protocols, irrespective of timing of hu-PBL reconstitution or site
      of transplantation. Although preactivation of hu-PBL did not improve the level of
      hu-PBL chimerism, histological and immunohistochemical analysis of the grafts
      revealed a severe human lymphocytic infiltration and beta cell destruction only
      in the grafts of mice receiving preactivated hu-PBL. This beta cell injury
      resulted in impaired glucose tolerance, with in some animals recurrence of
      hyperglycaemia, and decreased insulin and C-peptide levels after glucose
      stimulation. Therefore, we conclude that activation of hu-PBL prior to transfer
      is essential in achieving xenograft infiltration and destruction in hu-PBL-SCID
      mice. The need for immune manipulation suggests that interactions between hu-PBL
      and xenografts in this model may be hampered by incompatibilities in cross
      species adhesion and/or activation signals.

PMID- 10971527
TI  - Paradoxical vocal cord movement: a rare condition that is likely to be
      misdiagnosed and mistreated.

PMID- 10971526
TI  - CD14+CD16+ monocyte subpopulation in Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute febrile illness caused by vasculitis, occurring
      in early childhood. We have demonstrated that the activation of
      monocytes/macrophages plays a central role during acute KD. Recently, it has been
      reported that the CD14+CD16+ monocyte subpopulation plays a more important role
      in inflammation. In this study, we investigated the peripheral blood CD14+CD16+
      monocyte subpopulation by flow cytometry, and serum levels of IL-10 and IL-12
      using a sandwich ELISA in 28 KD patients. We also investigated this subpopulation
      in patients with bacterial infections, mononucleosis and anaphylactoid purpura,
      since the cause of KD remains unknown. We observed an increase in the number of
      CD14+CD16+ monocytes with acute KD, which was a positive correlation with C
      reactive protein levels, and we observed only the patients with severe bacterial
      infections had increased this subpopulation during the acute stage among control
      diseases. In addition, we found that the serum levels of IL-10, but not IL-12,
      were higher during acute KD. These data suggest that increased peripheral blood
      CD14+CD16+ monocytes are part of the regulatory system of monocyte function
      during acute KD.

PMID- 10971528
TI  - The role of history, Epworth Sleepiness Scale Score and body mass index in
      identifying non-apnoeic snorers.
AB  - Seventy-one adults referred with snoring over a 9-month period were assessed and
      their apnoeic-status determined by clinical assessment using symptoms suggestive
      of the obstructive sleep apnoea-hypopnoea syndrome, the Epworth Sleepiness Scale
      score (ESS) and body mass index (BMI). The results of clinical assessment were
      compared to that of overnight six-channel polysomnography where snoring noise
      level, pulse rate, capillary oxygen saturation, breathing effort, oronasal
      airflow and body position were monitored. Polysomnography detected an apnoea
      hypopnoea index (AHI) of < 15 episodes/h in 61(86%) patients and an AHI of > or =
      15 episodes/h in 10 (14%) patients. Clinical assessment alone identified 57
      patients with AHI of < 15 episodes/h as 'non-apnoeic snorers' and six patients
      with AHI of > or = 15 episodes/h as 'apnoeic snorers'. The sensitivity of this
      method of clinical assessment in identifying the 'non-apnoeic snorers' from
      amongst patients referred with snoring was 93.4% and its specificity was 60% (P <
      0.001).

PMID- 10971529
TI  - Re-evaluation of normative electronystagmography data in healthy ageing.
AB  - Previous work by our group questions the validity of existing
      electronystagmography (ENG) reference ranges in the elderly. We aim to establish
      valid reference ranges for ENG in people over 65 on the Nicolet Nystar Plus
      system. Ninety-six healthy asymptomatic subjects over 65 underwent ENG, including
      spontaneous and positional nystagmus, saccades, smooth pursuit, optokinetic
      nystagmus and bithermal calorics; 95% reference ranges with confidence intervals
      were calculated. The newly determined reference ranges were far wider than those
      provided by the ENG equipment manufacturer for eight out of 11 parameters (all P
      < 0.001). Vestibular function is known to deteriorate and become more variable
      with age. The failure to reflect this change in currently used reference ranges
      may have contributed to the high rates of vestibular disease reported in some
      series of dizzy elderly patients. Clinical interpretation of ENG depends on valid
      reference ranges.

PMID- 10971530
TI  - Pars tensa retraction pockets in children: treatment by excision and ventilation
      tube insertion.
AB  - Tympanic membrane retraction pockets involving the pars tensa are not uncommon in
      clinical practice. Recurrent infections, ossicular erosion and cholesteatoma are
      the recognized sequelae. The management options include surveillance, medical
      treatment and surgery. The surgical procedures range from grommet insertion to
      extensive tympanoplasty procedures. We report our experience with simple excision
      and grommet insertion, performed in 31 ears in 26 patients as day cases. The
      follow-up ranged from 8 to 34 months with a mean of 16 months. The procedure was
      successful in 23 ears (success rate of 74%). Recurrence of retraction occurred in
      seven ears and in one ear there was a persistent perforation. Age, previous
      grommet insertion and severity of retraction did not have a statistically
      significant influence on the final outcome. We conclude that excision and grommet
      insertion is a simple, safe and efficient procedure for the management of
      tympanic membrane retraction pockets and can be considered in preference to
      extensive tympanoplasty.

PMID- 10971531
TI  - Ossiculoplasty: autogenous bone grafts, 34 years experience.
AB  - A series of 785 bone grafts between the tympanic membrane and head of the stapes
      were performed between 1964 and 1998. Ears were divided into 'normal tympanic
      membrane', 'stage I' and 'stage II' groups, in which the averages of the last
      postoperative air-bone gaps were 13.2, 18.7 and 18.1 dB, respectively (revision
      operations included). In the same order 43%, 26% and 23% of the ears showed air
      bone gaps equal to or smaller than 10 dB; 85%, 61% and 67% equal to or smaller
      than 20 dB. Failures specific to the bone columella necessitated nine revision
      operations (eight for osseous fixation and one for atrophy). There have been no
      extrusions so far. Although, in the light of the literature the results are
      acceptable there is room for improvement.

PMID- 10971532
TI  - Guidelines on the diagnosis of noise-induced hearing loss for medicolegal
      purposes.
AB  - These guidelines aim to assist in the diagnosis of noise-induced hearing loss
      (NIHL) in medicolegal settings. The task is to distinguish between possibility
      and probability, the legal criterion being 'more probable than not'. It is argued
      that the amount of NIHL needed to qualify for that diagnosis is that which is
      reliably measurable and identifiable on the audiogram. The three main
      requirements for the diagnosis of NIHL are defined: R1, high-frequency hearing
      impairment; R2, potentially hazardous amount of noise exposure; R3, identifiable
      high-frequency audiometric notch or bulge. Four modifying factors also need
      consideration: MF1, the clinical picture; MF2, compatibility with age and noise
      exposure; MF3, Robinson's criteria for other causation; MF4, complications such
      as asymmetry, mixed disorder and conductive hearing impairment.

PMID- 10971533
TI  - The role of Mucodyne in reducing the need for surgery in patients with persistent
      otitis media with effusion.
AB  - A recent meta-analysis suggested a possible beneficial effect of
      carboxymethylcysteine (Mucodyne) in resolving otitis media with effusion (OME),
      but the methodology in several of the included trials was flawed. A double-blind
      randomised controlled trial (RCT) involving 163 patients (78 randomised to
      Mucodyne and 85 to placebo) was therefore performed. MAIN OUTCOME MEASURE:
      operative intervention or not. Of the 28 patients with resolved OME, 17 were in
      the Mucodyne group and 11 in the placebo group. Although it appeared that
      patients treated with Mucodyne were 1.68 times more likely to undergo resolution
      of OME than patients receiving placebo, this did not reach statistical
      significance. [Risk ratio of 1.68 (95% C.I., 0.74-3.37)]. chi2 test (df = 162) =
      2.24 (P = 0.134). The absolute risk difference in the study was 8.5% (95% C.I., 
      3-20). We cannot exclude the possibility that Mucodyne is as beneficial as a 20%
      additional resolution of OME, or as harmful as a 3% decrease in the resolution of
      OME.

PMID- 10971534
TI  - Performance assessment of ossicular chain reconstructions in a University
      hospital.
AB  - It remains to be demonstrated that normal, day-to-day routine surgery is as
      effective as it would appear from the literature, where the results of very
      experienced surgeons are presented. The object of this study was to measure our
      performance for ossicular chain reconstructions. One hundred and thirty-eight
      total and partial reconstructions performed by 13 different surgeons were
      evaluated. The population was divided into four different groups based on the
      presence or absence of the canal wall and stapes suprastructure. The results
      varied widely. A number of patients benefited greatly, whereas others experienced
      deterioration in their hearing. The best improvement (median 13 dB) was achieved
      in the group with an intact canal wall and absent stapes suprastructure. The
      postoperative air bone gap was better for autologous incus rather than prosthesis
      in the group where the canal wall and stapes were intact. There were three minor
      complications. This continuous feedback reports exceptional results (good and
      bad). The strengths and weaknesses of the department can be determined. This
      feedback indicates that this procedure is safe and beneficial for the patients in
      our Institution.

PMID- 10971535
TI  - Ossiculoplasty using hydroxyapatite prostheses: long-term results.
AB  - The surgical results of ossicular chain reconstruction using a hydroxyapatite
      prosthesis were evaluated in 106 ears of 101 patients who were followed up for >
      5 years. Successful reconstruction was defined as: (1) postoperative air-bone gap
      of </= 20 db; or (2) postoperative air conduction better than 40 db; or (3)
      hearing gain better than 15 db. Success in hearing was obtained in 63/106 ears
      (59%) at 1 year; 44/65 ears (68%) in P-type (short columella) and 19/41 ears
      (46%) in T-type (long columella). By the fifth year, the overall success rate had
      deteriorated to 50%: i.e. 39/65 ears (60%) in P-type and 14/41 ears (34%) in T
      type. Extrusion of the prosthesis occurred in 17 ears (16%) with a mean
      postoperative period of 27.7 months. The present results indicate that
      hydroxyapatite is a suitable material for an ossicular prosthesis, although the
      incidence of extrusion is high when it is placed in contact with the tympanic
      membrane.

PMID- 10971536
TI  - Magnetic resonance imaging results in patients with central electronystagmography
      findings.
AB  - The objective of this study was to determine the findings on magnetic resonance
      imaging (MRI) in patients identified as having central vestibular abnormalities
      on electronystagmography (ENG) testing, to discuss the issue of 'gold standard'
      in the investigation of central oculo-vestibular system diseases and to present a
      model for understanding this area. A retrospective review of the case notes of
      patients (n = 23) found to have central ENG findings at vestibular assessment and
      for whom MRI scanning data was available was undertaken. Each patient underwent a
      full ENG evaluation, including gaze, ocular-motor and caloric testing, and MRI.
      Only seven of the patients with central ENG findings had abnormal MRI scans.
      Thus, the incidence of the identification of structural abnormality on MRI in
      patients with central ENG findings is low. These investigations are complementary
      in the investigation of balance disorder patients.

PMID- 10971537
TI  - Testing the central vestibular functions: a clinical survey.
AB  - In vestibular examinations anomalies in the saccade and smooth pursuit tests as
      well as the fixation suppression after caloric stimulation might indicate central
      lesions in the vestibular system. Additionally, a high gain in the torsion test
      is suspicious of cerebellar dysfunction. In this study, 141 patients out of 973
      had at least one of these anomalies. For 125 patients we were able to compare the
      initial findings in the vestibular examination with the final diagnosis by
      otologists, neurologists and general practitioners. The complaints of 37.6% of
      the patients with these electronystagmographic (ENG) anomalies appeared to be of
      central origin. Abnormal saccades, an abnormal smooth pursuit, and an elevated
      gain in the torsion test were not independently diagnostic for central vestibular
      disease. The fixation suppression index appeared to be lower for subjects with
      peripheral vestibular disease. Otologists more often referred their patients to a
      neurologist if the fixation index was elevated.

PMID- 10971538
TI  - Uvulopalatopharyngoplasty versus laser assisted uvulopalatoplasty for the
      treatment of snoring: an objective randomised clinical trial.
AB  - This study was designed to evaluate objectively the clinical effectiveness of
      surgery for snoring and to compare the results of conventional
      uvulopalatopharyngoplasty (UPPP) and laser assisted uvulopalatoplasty (LAUP) in
      the treatment of snoring. Patients who had been referred for investigation and
      treatment of their snoring were randomly allocated to receive either UPPP or
      LAUP. Forty-seven patients with confirmed palatal flutter had surgery and all of
      them had a preoperative and postoperative objective assessment of their snoring
      loudness and duration in the home. The recording device (Snore Box) is simple for
      the patient to operate, portable with a built in microphone, and able to produce
      objective results, which can be automatically analysed. Of the 38 patients, who
      had technically valid recordings, 22 underwent LAUP and 16 UPPP. Overall the mean
      postoperative Snore Index (SI) was less than the preoperative SI (P < 0.0001),
      the average difference being 78.2 snores/h. There was no significant difference
      between the LAUP and UPPP regarding the fall in the SI. This study is the first
      objective comparative study to demonstrate the effectiveness of snoring surgery.

PMID- 10971539
TI  - Spiral computed tomography before and after cricothyroid approximation.
AB  - Cricothyroid approximation raises the vocal pitch by simulating the contraction
      of the cricothyroid muscle with sutures. The aim of this study was to determine
      the role of spiral computed tomography (CT) in patients scheduled for
      cricothyroid approximation. Twenty-nine transsexual patients were examined with
      spiral CT before and after laryngoplastic surgery. Computed tomography findings
      were correlated with phoniatric findings in all patients. The average reduction
      of the cricothyroid distance was 6 mm (range 2-10 mm). The vocal pitch elevation
      was more remarkable in the patient group with greater reduction of the
      cricothyroid distance. Computed tomography accurately determines the cricothyroid
      distance before and after surgery and is an ideal method for follow-up purposes,
      especially when there is a postoperative reversion towards a lower pitch. In
      addition, CT provides important data as to the most appropriate extent and site
      of intracordal intervention to be done for a desired pitch elevation.

PMID- 10971540
TI  - The effects of chronic otitis media with effusion on the measurement of
      distortion products of otoacoustic emissions: presurgical and postsurgical
      examination.
AB  - This study aims to determine the influence of middle ear effusion and inserted
      tympanostomy tubes on the feasibility of recording and of the amplitude of
      distortion product otoacoustic emissions (DPOAE). Effusion in the middle ear
      reduces the number of measurable responses and their amplitude in the whole range
      of frequencies from 0.5 to 8 kHz. These changes were more distinct in mucous than
      in serous effusion. There was an increase in the number of measurable responses
      and amplitude of DPOAE after surgery. Inserted tympanostomy tubes have no
      influence on the feasibility of DPOAE recording but reduce their amplitude in
      comparison to the control group.

PMID- 10971541
TI  - Nerve monitoring in thyroid surgery.

PMID- 10971542
TI  - The development of nuclear medicine in Finland: a review on the occasion of the
      40th anniversary of the Finnish Society of Nuclear Medicine.

PMID- 10971543
TI  - Digital X-ray radiogrammetry: a new appendicular bone densitometric method with
      high precision.
AB  - The precision of any given method for measurement of bone mineral density (BMD)
      is important in relation to the interpretation of repeated measurements over
      time, e.g. to monitor the course of suspected osteoporosis or follow the effect
      of therapy. In the present study a new bone densitometer using the digital X-ray
      radiogrammetry (DXR) method (Pronosco X-posure Systemtrade mark) is investigated
      with respect to its short-term precision. The study was carried out on two groups
      of females, one consisting of 20 women between the ages of 30 and 40, and the
      other of 20 post-menopausal women above the age of 64. The mean age of the
      premenopausal women was 35.2 years and the mean DXR BMD was 0.578 g cm-2. The
      mean age of the post-menopausal women was 68.2 years and the mean DXR BMD was
      0.489 g cm-2. The short-term precision of the two groups was evaluated using the
      coefficient of variation (CV%) and corresponding 90% confidence intervals. The
      coefficient of variation in the premenopausal group was 0.68% with a 90%
      confidence interval of 0. 57%-0.83%. The coefficient of variation in the
      postmenopausal group was 0.61% with a 90% confidence interval of 0.52-0.75%. It
      can be concluded from the present study that the short-term in vivo precision
      error of the DXR method is low in both pre- and post-menopausal women. When the
      results of the study are compared to data reported in the literature, the
      performance of the DXR method seems to be at least equivalent with peripheral
      DXA.

PMID- 10971544
TI  - Automated standardized pupillometry with optical method for purposes of clinical
      practice and research.
AB  - The aim of the current study was the introduction and standardization of two
      experimental conditions for dynamic pupillometry. Pupillometry is a method that
      can provide valuable data concerning the functioning of the autonomous nervous
      system. The system for recording the pupil reaction was developed in the
      Laboratory of Clinical Neurophysiology of the 1st Department of Neurology of
      Aristotle University of Thessaloniki, in co-operation with the Laboratory of
      Fluid Mechanics of the Aristotle University of Thessaloniki. This system is fully
      automated. It includes an infra-red video camera, which has the capacity to
      record in complete darkness, and an SLE (clinical photic stimulator) lamp. A
      software application automatically performed all the procedures. During the first
      experiment, one flash was administered. During the second experiment, a series of
      25 flashes (1 Hz frequency) was administered. Fifty physically and mentally
      healthy subjects aged 23-48 years took part in the study. Means, standard
      deviations and ranges for all variables characterizing normal subjects during
      both experimental conditions are reported. Test/re-test results and comparisons
      of the two eyes are also reported. The combined use of these two experimental
      conditions in dynamic pupillometry may be a very useful tool in medical research.
      There are already reports on the usefulness of pupillometry in the research of
      various diseases, including depression and Alzheimer's disease. It is expected
      that it will also be a valuable research tool in the study of diabetes,
      alcoholism, myasthenia gravis, cancer, multiple sclerosis, etc.

PMID- 10971545
TI  - Increased circulating levels of plasma ATP in cystic fibrosis patients.
AB  - Recent studies have shown that the cystic fibrosis transmembrane conductance
      regulator (CFTR), an ATP-binding cassette (ABC) transporter whose mutations are
      responsible for cystic fibrosis (CF), permeates ATP. However, little information
      is available concerning extracellular ATP concentrations in CF patients. Thus,
      the goal of this preliminary study was to determine the circulating levels of
      plasma ATP in CF patients. Circulating levels of plasma ATP were determined by
      the luciferin-luciferase assay in both CF patients and healthy volunteer control
      subjects. The two groups were compared using an analysis of variance. CF genotype
      and age, which ranged from 7 to 56 years, were also used to compare data by
      single-blind analysis. With comparable sample numbers, CF patients had
      statistically higher levels of circulating ATP (34%, P<0.01) when compared by
      analysis of covariance with the age of the subjects as the cofactor. The CF
      patients bearing the DeltaF508 genotype had a 54% (n=33, P<0.01) higher plasma
      ATP concentration compared to controls, while patients bearing other CF genotypes
      were similar to controls (n=10, P<0.4). We conclude that CF patients have higher
      circulating levels of ATP when compared to controls. Increased levels of plasma
      ATP, which is an important autocrine/paracrine hormone in many cell types, may be
      associated with chronic manifestations of the disease.

PMID- 10971547
TI  - Blood flow rate in arteriovenous anastomoses: from the cradle to the grave.
AB  - Blood flow rate was measured in the arteriovenous anastomoses (AVAs) in the
      cutaneous tissue of the pulp of the first toe in 15 children between 3 and 15
      years old, and in the pulp of the thumb and the first toe in 16 adults between 27
      and 93 years old (two subjects from each decade) by the heat-washout method. The
      examinations showed that AVA-blood flow rate decreased with increasing age, and
      the difference between children and adults was highly significant (P=0.001).
      Blood flow rate in the finger pulp was higher than in the toe pulp (P=0.025). No
      significant difference in blood flow rate was found in either thumb pulp or toe
      pulp between men and women.

PMID- 10971546
TI  - Insulin treatment increases skeletal muscle fibre area in patients with diabetes
      mellitus type 2.
AB  - The effects of insulin treatment on skeletal muscle characteristics were studied
      in 18 patients (62 +/- 11 years) with poorly controlled diabetes mellitus type 2
      (mean duration 7.5 +/- 6 years). Skeletal muscle biopsy samples were taken from
      the lateral portion of the quadriceps muscle before and after a period of insulin
      treatment of 40 +/- 14 days. Enzyme activities (phosphofructokinase, 3
      hydroxyacyl-CoA dehydrogenase, citrate synthase, lactate dehydrogenase and
      creatine kinase) and myoglobin content were assessed. In a subgroup of 11
      patients (60 +/- 11 years), skeletal muscle fibre type composition (type I, IIA,
      IIB and IIC) and fibre type cross-sectional area were also analysed. Following
      insulin treatment there were 32 and 38% increases, respectively, in the cross
      sectional areas of type IIA and IIB fast-twitch fibres (P<0. 02). The fibre type
      distribution did not change. The myoglobin content in muscle decreased by 20%
      (P<0.01). Of the enzymes tested, the 3-hydroxyacyl-CoA dehydrogenase activity
      decreased by 10% (P<0. 04). Serum glucose, HbA1C and serum triglyceride levels
      decreased (P<0.001) and body weight and arm muscle circumference increased
      (P<0.02). In conclusion, insulin treatment of patients with poorly controlled non
      insulin-dependent diabetes mellitus increased the fast-twitch fibre area, reduced
      myoglobin levels and decreased muscle enzyme activity related to fatty acid
      oxidation.

PMID- 10971548
TI  - Cardiac adrenergic innervation within the first 3 months after acute myocardial
      infarction.
AB  - It is widely accepted that myocardial infarction results in adrenergic
      denervation of the infarcted and peri-infarcted myocardium. On the contrary, the
      concept of re-innervation of adrenergic nerve fibres is less well established.
      Although there is evidence of partial re-innervation occuring several months
      after myocardial infarction, the extent and time scale of re-innervation are only
      poorly known. In this study we investigated changes in cardiac adrenergic
      innervation and myocardial perfusion during the early convalescence period (the
      first 3 months) after an acute myocardial infarction. Single-photon emission
      computed tomographic imaging was conducted in 15 men 1 week and 3 months after an
      acute myocardial infarction with I123-metaiodobentzylguanidine (MIBG) and Tc99m
      sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired
      perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake
      </=30% of maximal myocardial activity. The size of the MIBG defect calculated as
      a percentage of left ventricular mass remained unchanged between 1 week and 3
      months after myocardial infarction (31.1 +/- 17.3% vs. 30. 5 +/- 16.8%,
      respectively). Accordingly, MIBG activity of the infarct and peri-infarct zones
      (expressed as a percentage of MIBG activity of the myocardium with normal
      perfusion) showed no significant change (23.7 +/- 10.0% vs. 25.3 +/- 11.0% and
      39.0 +/- 11.3% vs. 40.8 +/- 12.8%, respectively) during the follow-up. On the
      other hand, the size of MIBI defect decreased significantly during the follow-up
      (14.2 +/- 11.5% vs. 11.4 +/- 9.7%, P<0.05, respectively) indicating improved
      myocardial perfusion. The results demonstrate that cardiac adrenergic re
      innervation is a slow process; despite a significant increase in myocardial
      perfusion we found no evidence of adrenergic re-innervation during the first 3
      months after acute myocardial infarction.

PMID- 10971549
TI  - Computerized analysis of video fluorescein imaging (VFI) of the skin.
AB  - Video fluorescein imaging (VFI) is a new technique to continuously follow the
      development of fluorescence in the skin, i.e. blood inflow and perfusion, after
      intravenous injection of sodium fluorescein. The method is supplementary to other
      microcirculatory techniques for evaluation of peripheral arterial occlusive
      disease, particularly in critical ischaemia. In the present article we describe a
      totally computerized digital imaging processing system for evaluation and present
      results from a comparison between the evaluations of the appearance and
      development of the fluorescence in the sole of the foot using the computerized
      and the previously used manual techniques. With the computerized system the
      images are stored and correlated with the start of the injection. Regions of
      interest are then marked and a mean value of fluorescence intensity is calculated
      for each image. Using this computerized system the time required for evaluation
      has been shortened to about 10 min. The results of the comparison between the
      manual and computerized evaluations of appearance times showed that a significant
      correlation existed in all examined parts of the feet between the two techniques.
      The methods gave approximately the same results in regions with fluorescence
      appearance times between 20 and 50 s. With longer appearance times than
      approximately 50 s a systematic difference between the two techniques seemed to
      exist. In this interval shorter appearance times were measured with the
      computerized technique than with the manual technique. However, the clinical
      information with regard to prognosis would be relatively unchanged when the new
      computerized assessment technique and a new cut-off level for the appearance time
      are used. Also, regarding the development of fluorescence after the appearance
      time, expressed by the slope, a significant correlation was found between the
      manual and the computerized evaluation.

PMID- 10971550
TI  - Effects of varying central command and muscle mass on the cardiovascular
      responses to isometric exercise.
AB  - To determine if the central command signal associated with isometric exercise is
      mass-dependent, 20 subjects (nine male, 11 female; 23 +/- 1 years) performed four
      5-min bouts of supine isometric exercise with a large (quadriceps; LEG) and small
      (forearm; ARM) muscle mass. For each extremity, one bout entailed maintaining a
      constant force (CF; 20% maximal voluntary contraction) and the other constant
      electromyographic activity (CE; approximately 20% MVC initially). Central command
      was assumed to increase with CF and remain unchanged with CE. Heart rate
      increased more with LEG than ARM (P<0.001) and, in LEG, was higher in CF than CE
      at min 5 (P<0.001). Mean arterial pressure was higher in LEG (P<0.001) by min 2
      and 10 +/- 3 mmHg higher in LEG CF than LEG CE by min 5 (P<0.001). Ratings of
      perceived exertion were highest in LEG CF (P<0.001); LEG CE did not differ from
      ARM CE (P<0.001) by min 4. The ARM responses did not differ between CF and CE in
      any variable. These data suggest that muscle mass influences the central command
      signal during isometric exercise and central command modulates this response in
      larger muscle masses.

PMID- 10971551
TI  - Pulmonary capillary blood flow by partial CO2 rebreathing: importance of the
      regularity of the respiratory pattern.
AB  - The partial CO2 rebreathing technique has been shown to be a reliable non
      invasive method for measurement of pulmonary capillary blood flow (Qc), but
      experience with this technique has been limited to controlled mechanical
      ventilation. In this study, we evaluated this technique during spontaneous and
      oriented ventilation in nine subjects without known cardiopulmonary disease.
      Subjects underwent 10 consecutive (Qc) measurements with both spontaneous and
      oriented ventilation. Breath-by-breath gas exchange was measured and (Qc) was
      calculated from changes in CO2 elimination and PETCO2, which were achieved by
      sudden increase of the apparatus deadspace (rebreathing period). An exponential
      curve was fitted to the PETCO2 values in the rebreathing period in order to
      estimate PETCO2 at equilibrium. We found that mean (Qc) values were not
      influenced by the ventilation pattern (P=0.51), but that the intra-individual
      variability with oriented ventilation (median=16.0%) was significantly lower than
      with spontaneous ventilation (median=31.8%, P=0.039). Accordingly, the curve
      fitting for rebreathing PETCO2 rise failed in 4.4% of measurements with oriented
      ventilation vs. 18.9% of measurements with spontaneous ventilation (P=0.039). Our
      results suggest that the performance of the partial CO2 rebreathing technique is
      adversely affected by spontaneous ventilation and, consequently, that this method
      should be reserved for patients with regular respiratory patterns.

PMID- 10971553
TI  - The role of dermatologists in the evolution of laser surgery.
AB  - The role dermatologists have played throughout the history of laser development
      is an extremely vital one. The initial interests of Dr. Leon Goldman stimulated
      many other individual dermatologists to further his work and develop surgical
      techniques using newer laser systems to provide more effective treatment for
      patients with a variety of skin diseases. The long list of current cutaneous
      laser applications developed by dermatologists makes it virtually certain that
      members of our specialty will continue to play a significant future role in the
      refinement of laser instrumentation and operative techniques that are inevitable
      to occur.

PMID- 10971552
TI  - Regional cerebral blood flow during hyperventilation in patients with acute
      bacterial meningitis.
AB  - Mechanical hyperventilation is often instituted in patients with acute bacterial
      meningitis when increased intracranial pressure is suspected. However, the effect
      on regional cerebral blood flow (CBF) is unknown. In this study, we measured
      regional CBF (rCBF) in patients with acute bacterial meningitis before and during
      short-term hyperventilation. In 17 patients with acute bacterial meningitis,
      absolute rCBF (in ml/100 g min-1) was measured during baseline ventilation and
      hyperventilation by single-photon emission computed tomography (SPECT) using
      intravenous 133Xe bolus injection. Intravenous 99mTc-HMPAO
      (hexamethylpropyleneamine oxime) was subsequently given during hyperventilation.
      In 12 healthy volunteers, rCBF was measured by SPECT and 99mTc-HMPAO during
      spontaneous ventilation. Using standard templates to identify regions of interest
      (ROIs), we calculated rCBF in percentage of cerebellar (99mTc-HMPAO images) or
      mean hemispheric (133Xe images) flow for each ROI, the degree of side-to-side
      asymmetry for each ROI, and the anterior-to-posterior flow ratio. On 133Xe
      images, absolute rCBF decreased significantly during hyperventilation compared to
      baseline ventilation in all regions, but the relative rCBF did not change
      significantly from baseline ventilation (n=14) to hyperventilation (n=12),
      indicating that the perfusion distribution was unchanged. On 99mTc-HMPAO images
      (n=12), relative rCBF and the anterior-to-posterior flow ratio were significantly
      lower in patients than in controls in the frontal and parietal cortex as well as
      in the basal ganglia. Focal perfusion abnormalities were present in 10 of 12
      patients. Regional cerebral blood flow abnormalities are frequent in patients
      with acute bacterial meningitis. Short-term hyperventilation does not enhance
      these abnormalities.

PMID- 10971554
TI  - Treatment of poikiloderma of Civatte with an intense pulsed light source.
AB  - BACKGROUND: Effective treatment of poikiloderma of Civatte combines elimination
      of both the vascular and pigmented components simultaneously. A broad spectrum,
      noncoherent, intense pulsed light (IPL) source delivers multiple wavelengths with
      software controlled pulse durations and sequencing, which permits treatment of
      both vascular and pigmented lesions simultaneously. OBJECTIVE: To determine
      response and side effects of poikiloderma of Civatte of the neck and chest when
      treated by IPL. METHODS: One hundred and thirty-five patients randomly selected
      with typical changes of poikiloderma of Civatte on the neck and/or upper chest
      were treated with one to five treatments using IPL. RESULTS: Clearance of more
      than 75% of telangiectasias and hyperpigmentation comprising poikiloderma was
      observed. The incidence of side effects was 5%, including pigment changes. In
      many cases, improved skin texture was noted both by physician and patient.
      CONCLUSION: IPL is an effective mode of therapy for poikiloderma of Civatte. It
      offers a reduction of pigment and telangiectasias with a low risk profile.
      Additional benefits include subjective changes of improvement in skin texture.

PMID- 10971555
TI  - Granulation tissue flap technique in extensive wounds for covering exposed bone
      after tumor excision.
AB  - BACKGROUND: Second intention partial wound healing followed by skin grafting is a
      well-established method in dermatosurgery. In wide tumor excision, where
      periosteum is removed, growth of granulation tissue in the central areas of bare
      bone can be prolonged. OBJECTIVE: We describe a new technique for a faster,
      reliable closure of large defects utilizing granulation tissue flaps. METHODS:
      Postoperative wounds were treated with wet dressings until granulation tissue had
      developed on the wound edges. The central defects were then covered with lateral
      granulation tissue flaps. Subsequently split skin grafting was performed.
      RESULTS: Thirty-eight patients (37-99 years old) were treated between 1991 and
      1999. Skin defects were located primarily on the scalp and forehead, and ranged
      from 3 to 13 cm in diameter. Wound bed preparation for skin grafting was achieved
      in all patients. Only minor complications, such as partial granulation flap
      necrosis in 5 of 38 patients or delayed skin graft healing in 4 of 38 patients,
      were seen. CONCLUSIONS: This technique for the closure of extensive skin defects
      is safe and effective.

PMID- 10971556
TI  - Noninvasive rejuvenation of photodamaged skin using serial, full-face intense
      pulsed light treatments.
AB  - BACKGROUND: Photodamaged skin is characterized not only by rhytides, but also by
      epidermal and dermal atrophy, rough skin texture, irregular pigmentation,
      telangiectasias, laxity, and enlarged pores. There is growing interest in the
      development of noninvasive methods to treat photodamaged skin. Skin
      photorejuvenation is the visible improvement of photodamaged skin using a laser
      or other light source. A noncoherent, broadband, pulsed light source is effective
      in the treatment of vascular and pigmented lesions of the skin. This study
      evaluates the role of intense pulsed light in the rejuvenation of photo aged
      skin. OBJECTIVE: The purpose of this study was to evaluate and quantify the
      degree of visible improvement in photodamaged skin following a series of full
      face, intense pulsed light treatments. METHODS: Forty-nine subjects with varying
      degrees of photo-damage were treated with a series of four or more full-face
      treatments at 3-week intervals using a nonablative, nonlaser intense pulsed
      visible light source. Fluences varied from 30 to 50 J/cm2. Subject evaluation and
      skin biopsies were used to assess treatment results. RESULTS: All aspects of
      photodamage including wrinkling, skin coarseness, irregular pigmentation, pore
      size, and telangiectasias showed visible improvement in more than 90% of subjects
      with minimal downtime and no scarring. Eighty-eight percent of subjects were
      satisfied with the overall results of their treatments. CONCLUSION: Treatment of
      photodamaged facial skin using a series of full-face treatments with intense
      pulsed light is a new and effective noninvasive method of skin rejuvenation with
      minimal risk and no patient downtime.

PMID- 10971557
TI  - Dispelling the myth of the required high hairline in follicular unit hair
      transplantation.
AB  - BACKGROUND: Hair restoration surgeons have historically taught that the hairline
      should be placed high on men undergoing hair restoration surgery. OBJECTIVE: To
      evaluate the position of the anterior-most aspect of the frontal forelock on men
      experiencing type III-V male pattern baldness. METHODS: Twenty men, ages 20-46
      years, with type III-V male pattern baldness were evaluated for the distances
      between the chin to nose, nose to eyebrows, and eyebrows to frontal forelock.
      RESULTS: The mean distance from chin to nose was 6.96 cm. The mean distance from
      nose to eyebrows was 6.55 cm. The mean distance from eyebrows to hairline was 6.8
      cm. The distance from chin to hairline was 20.3 cm. Therefore the eyebrows to
      hairline distance was 33.4% of the whole. CONCLUSION: When using follicular
      transplantation, it may be appropriate at times to divide the face into thirds at
      the time of hairline development.

PMID- 10971558
TI  - Clonidine premedication decreases propofol consumption during bispectral index
      (BIS) monitored propofol-ketamine technique for office-based surgery.
AB  - BACKGROUND: Propofol-ketamine anesthesia is a room air, spontaneous ventilation
      (RASV), dissociative intravenous (IV) sedation technique reported to have a near
      zero postoperative nausea and vomiting (PONV) rate. Clonidine premedication has
      been reported to control blood pressure intra- and postoperatively, as well as to
      reduce the requirements for hypnotic agents. The bispectral index (BIS) monitor
      is a reproducible, objective, observer independent, quantitative measurement of
      the hypnotic state. OBJECTIVE: This study was designed to compare the propofol
      consumption rate during BIS monitored propofol-ketamine anesthesia for office
      based, elective female facial rhytidectomy in patients with and without clonidine
      premedication. METHODS: Six patients receiving clonidine (200 microg oral
      premedication administered 30-60 minutes prior to induction of anesthesia were
      compared with a recent, historical control group of six patients who received no
      premedication. A BIS of 60-70 was chosen as the standard of comparison for light
      hypnotic state. A dilute propofol solution was used to gradually titrate
      anesthesia to a BIS of 60-70 prior to the administration of ketamine. RESULTS: A
      statistically significant reduction in propofol consumption was observed in the
      clonidine premedicated female elective rhytidectomy patients compared with those
      not receiving the clonidine. Other than modestly increased requirements for IV
      fluids, there were no adverse effects observed with clonidine premedication.

PMID- 10971559
TI  - Complete spontaneous regression of Merkel cell carcinoma: a review of the 10
      reported cases.
AB  - BACKGROUND: Merkel cell (neuroendocrine) carcinoma (MCC) is a very aggressive
      primary cutaneous neoplasm occurring most often on the head and neck of the
      elderly. Complete spontaneous regression (CSR) of MCC was first described in
      1986. Since then other cases have been reported bringing the total to 10.
      OBJECTIVE: To review these 10 cases and obtain long-term follow-up data, to
      compare them for similarities and differences. METHOD: Each original case report
      was extensively reviewed and authors contacted in most cases for confirmation and
      updated information. RESULTS: In no case did MCC recur after CSR was noted,
      although follow-up information in some cases was short. When CSR occurred, it was
      swift and dramatic with complete regression of skin and lymph node metastasis in
      1-3 months. CONCLUSION: While only 10 cases of CSR is a small number, MCC is
      itself a rare malignancy with just over 600 reported cases. Today most cases of
      MCC receive aggressive combined therapy effectively precluding diagnosis of CSR.
      The nature of regression in these 10 cases may point toward future immunologic
      therapy just as similar cases of CRS in patients with melanoma have led to
      advances in the immunologic treatment for that malignancy.

PMID- 10971560
TI  - Postacne scarring: a review of its pathophysiology and treatment.
AB  - BACKGROUND: There has been a largely unheralded revolution in the number of
      techniques that can now be used in the treatment of atrophic postacne scarring.
      Atrophic scarring is the more common type of scarring encountered after acne.
      OBJECTIVE: To illustrate the range of techniques useful in the therapy of
      postacne scarring, their relative advantages and disadvantages, and their place
      in treatment. METHOD: A review of available techniques is used to illustrate the
      treatment of indented or atrophic acne scars. RESULTS: The individual
      architecture of the indented scar must be assessed so that treatment may be
      designed to maximize its improvement. A variety of new methods now exist,
      including newer resurfacing tools such as infrared lasers, dermasanding, and
      others in their infancy such as nonablative resurfacing and radiofrequency
      methods. A true explosion in autologous and nonautologous tissue augmentation and
      the advent of tissue undermining and the use of punch replacement techniques has
      added more precision and efficacy to the treatment of these scars. CONCLUSION:
      Atrophic postacne scars may be satisfactorily treated in many patients, but
      multiple methods are often required to ensure the best results.

PMID- 10971561
TI  - A visit to the office of Jean Carruthers.

PMID- 10971562
TI  - Trichoid basal cell carcinoma found in a dilated pore on the nose.
AB  - A pore of Winer is a common, benign epidermal appendageal tumor arising from a
      hair follicle. We present a case where routine removal of a pore of Winer
      revealed the presence of a trichoid basal cell carcinoma. We describe the history
      of these lesions, discuss clinical and histologic differential diagnoses, and
      propose an explanation for the presence of these tumor cells. No prior report of
      basal cell carcinoma within a pore of Winer has been documented in the
      literature.

PMID- 10971563
TI  - Brooke-Spiegler syndrome: treatment of cylindromas with CO2 laser.
AB  - Brooke-Spiegler syndrome is an autosomal dominant inherited disease characterized
      by the development of multiple trichoepitheliomas and cylindromas. We report two
      patients with Brooke-Spiegler syndrome whose scalp cylindromas were treated with
      a high-energy continous wave CO2 laser after debulking with bipolar scissors in
      one of the patients. The special feature in our report is the coexistence of
      three adnexal skin neoplasms in one case, and the close association of cylindroma
      and eccrine spiradenoma in the same lesion. We also support that debulking with
      bipolar scissors prior to laser therapy can be a technique of great benefit in
      large tumors.

PMID- 10971564
TI  - Lasers play a useful role in periorbital incisional surgery.

PMID- 10971565
TI  - Cold steel surgery for blepharoplasty.

PMID- 10971566
TI  - Cascading epicanthal skin resection and aesthetic reconstruction.
AB  - BACKGROUND: Drooping, cascading epicanthal skin is a common phenomenon in the
      elderly, but its surgical removal and reconstruction has not been documented.
      OBJECTIVE: A surgical technique is described to quickly and efficiently remove
      excessively drooping epicanthal tissue and to reconstruct an aesthetically
      pleasing lateral nose to epicanthal area. METHOD: Photographs of a woman with
      severe involvement are utilized to portray the surgical methodology. RESULTS:
      Reconstruction of an acceptable lateral nose to epicanthal concavity was easily
      and safely accomplished. CONCLUSION: Excessive lateral nose and epicanthal skin
      can be removed and the area reconstructed by the described technique using local
      anesthesia in a simple operation.

PMID- 10971567
TI  - Lessons on dermoscopy #7. The diagnosis was thrombosed hemangioma.

PMID- 10971568
TI  - Lessons on dermoscopy #8. A high-risk melanocytic lesion.

PMID- 10971569
TI  - Cryosurgery acne attachment for actinic cheilitis.

PMID- 10971571
TI  - Reply

PMID- 10971570
TI  - Regarding closure method to treat incompetent saphenofemoral junction/ greater
      saphenous vein.

PMID- 10971572
TI  - Regarding liposuction in patients over the age of 40.

PMID- 10971573
TI  - Reply

PMID- 10971574
TI  - Why would anyone bother with "the lateral femoral cutaneous nerve block" for
      harvesting split-thickness grafts?

PMID- 10971575
TI  - A tribute to sulfur.
AB  - Recent progress in a number of areas of biochemistry and biology has drawn
      attention to the critical importance of sulfur in the biosynthesis of vital
      cofactors and active sites in proteins, and in the complex reaction mechanisms
      often involved. This brief review is intended as a broad overview of this
      currently rapidly moving field of sulfur biochemistry, for those who are
      interested or are involved in one or the other aspect of it, a synopsis by one
      who has stumbled into this field from several directions in the course of time.
      Only for iron are metal-sulfur relationships discussed in detail, as the iron
      sulfur subfield is one of the most active areas.

PMID- 10971576
TI  - Episomal vectors for gene expression in mammalian cells.
AB  - An important reason for preferring mammalian cells for heterologous gene
      expression is their ability to make authentic proteins containing post
      translational modifications similar to those of the native protein. The
      development of expression systems for mammalian cells has been ongoing for
      several years, resulting in a wide variety of effective expression vectors. The
      aim of this review is to highlight episomal expression vectors. Such episomal
      plasmids are usually based on sequences from DNA viruses, such as BK virus,
      bovine papilloma virus 1 and Epstein-Barr virus. In this review we will mainly
      focus on the improvements made towards the usefulness of these systems for gene
      expression studies and gene therapy.

PMID- 10971578
TI  - Cytoprotective antioxidant function of tyrosine and tryptophan residues in
      transmembrane proteins.
AB  - The transmembrane domains of integral membrane proteins show an astounding
      accumulation of tyrosine and tryptophan residues, especially in the region of the
      highest lipid density. We found that these residues perform vital antioxidant
      functions inside lipid bilayers and protect cells from oxidative destruction.
      First, tyrosine- and tryptophan-containing peptides representing stretches from
      the transmembrane domains of different integral membrane proteins, including
      presenilin and the cystic fibrosis transmembrane conductance regulator, prevent
      oxidative lysis in clonal and primary cells. Second, long-chain acylated tyrosine
      and tryptophan, but not phenylalanine or short-chain acylated derivatives, are
      potent inhibitors of lipid peroxidation and oxidative cell death. The antioxidant
      functions of tyrosine and tryptophan may provide a specific explanation for (a)
      their unique transmembrane distribution pattern and (b) the high vulnerability of
      low-protein neuronal membranes to oxidative stress, as seen in neurodegenerative
      disorders.

PMID- 10971577
TI  - Expression and characterization of Edg-1 receptors in rat cardiomyocytes: calcium
      deregulation in response to sphingosine 1-phosphate.
AB  - Recent evidence indicates that sphingolipids are produced by the heart during
      hypoxic stress and by blood platelets during thrombus formation. It is therefore
      possible that sphingolipids may influence heart cell function by interacting with
      G-protein-coupled receptors of the Edg family. In the present study, it was found
      that sphingosine 1-phosphate (Sph1P), the prototypical ligand for Edg receptors,
      produced calcium overload in rat cardiomyocytes. The cDNA for Edg-1 was cloned
      from rat cardiomyocytes and, when transfected in an antisense orientation,
      effectively blocked Edg-1 protein expression and reduced the Sph1P-mediated
      calcium deregulation. Taken together, these results demonstrate that
      cardiomyocytes express an extracellular lipid-sensitive receptorsystem that can
      respond to sphingolipid mediators. Because the major source of Sph1P is from
      blood platelets, we speculate that Edg-mediated Sph1P negative inotropic and
      cardiotoxic effects may play important roles in acute myocardial ischemia where
      Sph1P levels are probably elevated in response to thrombus.

PMID- 10971579
TI  - Increased formation of reactive oxygen species due to glucose depletion in
      primary cultures of rat thymocytes inhibits proliferation.
AB  - Glycolytic glucose degradation to lactate is the only way of energy production in
      mammalian cells that does not use oxygen, and is thus a means of reducing
      oxidative stress. The aim of this work was to study the effect on proliferation
      of progressive glucose depletion during the cell cycle of stimulated cultured rat
      thymocytes. It has been shown that under conditions of limited glucose supply,
      these cells increase the generation of reactive oxygen species. Because of the
      sensitivity of the stimulating transcription factor Sp1 to redox changes with
      respect to its DNA binding, gene expression of glycolytic enzymes is markedly
      suppressed. As a consequence, cell division does not occur in glucose depleted
      thymocytes.

PMID- 10971580
TI  - Characterization of human HtrA2, a novel serine protease involved in the
      mammalian cellular stress response.
AB  - Human HtrA2 is a novel member of the HtrA serine protease family and shows
      extensive homology to the Escherichia coli HtrA genes that are essential for
      bacterial survival at high temperatures. HumHtrA2 is also homologous to human
      HtrA1, also known as L56/HtrA, which is differentially expressed in human
      osteoarthritic cartilage and after SV40 transformation of human fibroblasts.
      HumHtrA2 is upregulated in mammalian cells in response to stress induced by both
      heat shock and tunicamycin treatment. Biochemical characterization of humHtrA2
      shows it to be predominantly a nuclear protease which undergoes autoproteolysis.
      This proteolysis is abolished when the predicted active site serine residue is
      altered to alanine by site-directed mutagenesis. In human cell lines, it is
      present as two polypeptides of 38 and 40 kDa. HumHtrA2 cleaves beta-casein with
      an inhibitor profile similar to that previously described for E. coli HtrA, in
      addition to an increase in beta-casein turnover when the assay temperature is
      raised from 37 to 45 degrees C. The biochemical and sequence similarities between
      humHtrA2 and its bacterial homologues, in conjunction with its nuclear location
      and upregulation in response to tunicamycin and heat shock suggest that it is
      involved in mammalian stress response pathways.

PMID- 10971581
TI  - Suitable experimental conditions are required to characterize interferon-alpha2b
      synthetic peptides.
AB  - The binding and antiproliferative activities of synthetic peptides 29-35 and 122
      139 of interferon-alpha2b, both of which contain a cysteine residue in their
      sequences, were studied in the presence or absence of a dissociation medium
      containing mainly urea, dithiothreitol and 2-mercaptoethanol. Although interferon
      alpha2b peptides either did not modify or slightly increased 125I-labelled
      interferon-alpha2b specific binding to WISH cell-membrane receptors in the
      absence of dissociation medium, significant binding inhibition was obtained when
      both peptides were assayed in dissociation medium. Furthermore, also in the
      presence of dissociating agents, the two fragments inhibited cell growth in a
      concentration-dependent manner, the 122-139 sequence being more effective than
      the 29-35 sequence. No additive effect on interferon binding and cell
      proliferation was observed when both peptides were added simultaneously. Results
      obtained after submitting peptide 122-139 to gel filtration or PAGE under
      different experimental conditions showed the presence of dimers and/or
      noncovalent aggregates arising from intermolecular disulfide bridges or
      hydrophobic interactions. Thus, our results indicated that peptide effects on
      125I-labelled interferon-alpha2b binding and WISH cell proliferation were clearly
      manifested when the amount of monomeric species increased, showing that suitable
      experimental conditions should be used to study peptide behavior. The ability of
      both peptides to effectively trigger an interferon-specific biological action,
      such as cell growth inhibition, strongly suggested that 29-35 and 122-139
      interferon-alpha2b fragments constitute the conformational epitope or mimotope
      that interacts with the cytokine-specific receptor.

PMID- 10971582
TI  - Structural analysis of the lipopolysaccharide from Chlamydophila psittaci strain
      6BC.
AB  - The lipopolysaccaride of Chlamydophila psittaci 6BC was isolated from tissue
      culture-grown elementary bodies using a modified phenol/water procedure followed
      by extraction with phenol/chloroform/light petroleum. Compositional analyses
      indicated the presence of 3-deoxy-Dmanno-oct-2-ulosonic acid, GlcN, organic bound
      phosphate and fatty acids in a molar ratio of approximately 3. 3 : 2 : 1.8 : 4.6.
      Deacylated lipopolysaccharide was obtained after successive microscale treatment
      with hydrazine and potassium hydroxide, and was then separated by high
      performance anion-exchange chromatography into two major fractions, the
      structures of which were determined by 600 MHz NMR spectroscopy as alpha-Kdo-(2-
      >8)-alpha-Kdo-(2-->4)-alpha-Kdo-(2-->6)-beta-D-GlcpN -(1 -->6)-alpha-D-GlcpN 1,4'
      bisphosphate and alpha-Kdo-(2-->4)-[alpha-Kdo-(2-->8)]-alpha-Kdo-(2-->4)-alpha
      Kdo-(2- ->6)-beta-D-GlcpN-(1-->6)-alpha-D-GlcpN 1,4'-bisphosphate. The
      distribution of fatty acids in lipid A was determined by compositional analyses
      and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      experiments on lipid A and de-O-acylated lipid A. It was shown that the
      carbohydrate backbone of lipid A is replaced by a complex mixture of fatty acids,
      including long-chain and branched (R)-configured 3-hydroxy fatty acids, the
      latter being exclusively present in an amide linkage.

PMID- 10971584
TI  - The unusual dodecameric ferritin from Listeria innocua dissociates below pH 2.0.
AB  - The stability of the dodecameric Listeria innocua ferritin at low pH values has
      been investigated by spectroscopic methods and size-exclusion chromatography. The
      dodecamer is extremely stable in comparison to the classic ferritin tetracosamer
      and preserves its quaternary assembly at pH 2.0, despite an altered tertiary
      structure. Below pH 2.0, dissociation into dimers occurs and is paralleled by the
      complete loss of tertiary structure and a significant decrease in secondary
      structure elements. Dissociation of dimers into monomers occurs only at pH 1.0.
      Addition of NaCl to the protein at pH 2.0 induces structural changes similar to
      those observed upon increasing the proton concentration, although dissociation
      proceeds only to the dimer stage. Addition of sulfate at pH values >/= 1.5
      prevents the dissociation of the dodecamer. The role played by hydrophilic and
      hydrophobic interactions in determining the resistance to dissociation of L.
      innocua ferritin at low pH is discussed in the light of its three-dimensional
      structure.

PMID- 10971583
TI  - Novel polyunsaturated n-alkenes in the marine diatom Rhizosolenia setigera.
AB  - Four previously unknown n-C25 and n-C27 heptaenes of the marine diatom
      Rhizosolenia setigera were isolated and identified using NMR spectroscopy. They
      possess six methylene interrupted (Z)-double bonds starting at C-3 and an
      additional terminal or n-2 (Z)-double bond. Structural and stable carbon isotopic
      evidence suggests that these polyenes are biosynthesized by chain elongation of
      the C22:6n-3 fatty acid, followed by decarboxylation and introduction of double
      bonds at specific positions.

PMID- 10971585
TI  - Purification and cloning of pierisin-2, an apoptosis-inducing protein from the
      cabbage butterfly, Pieris brassicae.
AB  - The cabbage butterfly Pieris rapae contains a strong apoptosis-inducing
      substance, pierisin, against human cancer cell lines, which is thought to act via
      ADP-ribosylation. Here we report the purification and cloning of an apoptosis
      inducing substance, designated as pierisin-2, from another cabbage butterfly,
      Pieris brassicae. Pierisin-2 was purified from pupae by sequential chromatography
      and its cytotoxic and apoptosis-inducing activities to various cancer cells were
      similar to those of pierisin, designated as pierisin-1, from P. rapae. cDNA
      cloning of pierisin-2 was performed on the basis of the partial amino-acid
      sequence. The nucleotide sequence indicated that the cDNA encodes an 850-amino
      acid protein with a calculated molecular mass of 97 986. The deduced amino-acid
      sequence of pierisin-2 was 91% identical with that of pierisin-1. In vitro
      expressed protein in the reticulocyte lysate exhibited apoptosis-inducing
      activities against human gastric carcinoma TMK-1 and cervical carcinoma HeLa
      cells, similar to the purified native pierisin-2 from the pupae. Pierisin-2 shows
      regional sequence similarities with certain ADP-ribosylating toxins such as the A
      subunit of cholera toxin. The results from site-directed mutagenesis at Glu165, a
      conserved residue among ADP-ribosylating enzymes necessary for NAD binding, and
      from experiments with ADP-ribosylating enzyme inhibitors suggested that pierisin
      2 could be considered as an ADP-ribosylating toxin like pierisin-1.

PMID- 10971586
TI  - The LCCL module.
AB  - Here we show that Lgl1 protein, cub-1-related proteins, coch-5b2-related
      proteins, coagulation factor C of horse-shoe crab and a predicted protein of
      Plasmodium falciparum share a homologous domain. Since this domain-type was first
      identified in Limulus factor C, Coch-5b2 and Lgl1 we propose the name LCCL for
      this domain-family. The LCCL module of coch-5b2 is of special biological interest
      because it has been shown recently that mutations affecting this module cause the
      deafness disorder DFNA9 in humans. With a view to defining the structure and
      function of the LCCL domain of human coch-5b2 protein, we have expressed it in
      Escherichia coli and subjected it to preliminary structural characterization.
      Structure prediction and circular dichroism studies on the recombinant protein
      indicate that the domain possesses both alpha helices and beta strands. It is
      shown that the mutations which cause hearing loss in humans affect residues that
      are critical for the integrity of the LCCL module of the coch-5b2 protein.

PMID- 10971587
TI  - Glycosylation sites in the atrial natriuretic peptide receptor: oligosaccharide
      structures are not required for hormone binding.
AB  - Atrial natriuretic peptide (ANP) is a hormone involved in cardiovascular
      homeostasis through its natriuretic and vasodilator actions. The ANP receptor
      that mediates these actions is a glycosylated transmembrane protein coupled to
      guanylate cyclase. The role of glycosylation in receptor signaling remains
      unresolved. In this study, we determined, by a combination of HPLC/MS and Edman
      sequencing, the glycosylation sites in the extracellular domain of ANP receptor
      (NPR-ECD) from rat expressed in COS-1 cells. HPLC/MS analysis of a tryptic digest
      of NPR-ECD identified five glycosylated peptide fragments, which were then
      sequenced by Edman degradation to determine the glycosylation sites. The data
      revealed Asn-linked glycosylation at five of six potential sites. The type of
      oligosaccharide structure attached at each site was deduced from the observed
      masses of the glycosylated peptides as follows: Asn13 (high-mannose), Asn180
      (complex), Asn306 (complex), Asn347 (complex), and Asn395 (high-mannose and
      hybrid types). Glycosylation at Asn180 and Asn347 was partial. The role of
      glycosyl moieties in ANP binding was examined by enzymatic deglycosylation of NPR
      ECD followed by binding assay. NPR-ECD deglycosylated with endoglycosidase F2 and
      endoglycosidase H retained ANP-binding activity and showed an affinity for ANP
      similar to that of untreated NPR-ECD. Endoglycosidase treatment of the full
      length ANP receptor expressed in COS-1 cells also had no detectable effect on ANP
      binding. These results suggest that, although glycosylation may be required for
      folding and transport of the newly synthesized ANP receptor to the cell surface,
      the oligosaccharide moieties themselves are not involved in hormone binding.

PMID- 10971588
TI  - Characterization of the interaction of IpaB and IpaD, proteins required for entry
      of Shigella flexneri into epithelial cells, with a lipid membrane.
AB  - Entry of Shigella flexneri into epithelial cells and lysis of the phagosome
      involve the IpaB, IpaC, and IpaD proteins, which are secreted by type III
      secretion machinery. We report here the purification of IpaB and IpaD and the
      characterization of their lipid-binding properties as a function of pH. The
      interaction of IpaB with the membrane was quite independent of the pH whereas
      that of IpaD took place only at low pH. To support the data obtained with the
      purified proteins, we designed a system in which protein secretion by live
      bacteria was induced in the presence of liposomes, thereby allowing interaction
      of proteins with lipids directly after secretion and bypassing any purification
      step. In these conditions, both IpaB and IpaC, as well as minor amounts of IpaA
      and IpgD, were associated with the membrane and the ratio of IpaB to IpaC was
      modulated by the pH. The relevance of these results with respect to the dual
      roles of IpaB, IpaC and IpaD in induction of membrane ruffles and lysis of the
      endosomal membrane is discussed.

PMID- 10971589
TI  - Changes to the length of the flexible linker region of the Rieske protein impair
      the interaction of ubiquinol with the cytochrome bc1 complex.
AB  - Crystal structures of the cytochrome bc1 complex indicate that the catalytic
      domain of the Rieske iron-sulfur protein, which carries the [2Fe-2S] cluster, is
      connected to a transmembrane anchor by a flexible linker region. This flexible
      linker allows the catalytic domain to move between two positions, proximal to
      cytochrome b and cytochrome c1. Addition of an alanine residue to the flexible
      linker region of the Rieske protein lowers the ubiquinol-cytochrome c reductase
      activity of the mitochondrial membranes by one half and causes the apparent Km
      for ubiquinol to decrease from 9.3 to 2.6 microM. Addition of two alanine
      residues lowers the activity by 90% and the apparent Km decreases to 1.9 microM.
      Deletion of an alanine residue lowers the activity by approximately 40% and the
      apparent Km decreases to 5.0 microM. Addition or deletion of an alanine residue
      also causes a pronounced decrease in efficacy of inhibition of ubiquinol
      cytochrome c reductase activity by stigmatellin, which binds analogous to
      reaction intermediates of ubiquinol oxidation. These results indicate that the
      length of the flexible linker region is critical for interaction of ubiquinol
      with the bc1 complex, consistent with electron transfer mechanisms in which
      ubiquinol must simultaneously interact with the iron-sulfur protein and
      cytochrome b.

PMID- 10971590
TI  - Isolation, synthesis and pharmacological characterization of delta-palutoxins IT,
      novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae).
AB  - Four novel insecticidal toxins were isolated from the venom of the spider
      Paracoelotes luctuosus (Araneae: Amaurobiidae) and named delta-palutoxins IT1 to
      IT4. The four toxins are homologous 36-37 amino acid peptides reticulated by four
      disulfide bridges and three have amidated C-terminal residues. The delta
      palutoxins are highly homologous with the previously described mu-agatoxins and
      curtatoxins (77-97%). The four peptides demonstrated significant toxicity against
      larvae of the crop pest Spodoptera litura (Lepidoptera: Noctuidae) in a
      microinjection bioassay, with LD50 values in the 9-50 microg per g of insect
      range. This level of toxicity is equivalent to that of several of the most active
      scorpion toxins used in the development of recombinant baculoviruses, and the
      delta-palutoxins appear to be insect specific. Electrophysiological experiments
      demonstrated that delta-palutoxin IT1, the most active toxin acts by affecting
      insect sodium channel inactivation, resulting in the appearance of a late
      maintained sodium current, in a similar fashion to insecticidal scorpion alpha
      and alpha-like toxins and is thus likely to bind to channel receptor site 3.
      However, delta-palutoxin IT1 was distinguished by its lack of effect on peak
      sodium conductance, on the early phase of sodium current inactivation and the
      absence of a shift in the activation voltage of the sodium channels. delta
      Palutoxins are thus proposed as new insecticidal toxins related to the alpha and
      alpha-like scorpion toxins. They will be useful both in the development of
      recombinant baculoviruses in agrochemical applications and also as molecular
      probes for the investigation of molecular mechanisms of insect selectivity and
      structure and function of sodium channels.

PMID- 10971591
TI  - The helix nucleation site and propensity of the synthetic mitochondrial
      presequence of ornithine carbamoyltransferase.
AB  - This study describes the helix nucleation site and helix propagation of the
      amphiphilic helical structure of the mitochondrial presequence of rat ornithine
      carbamoyltransferase. We investigated this property of the 32-residue synthetic
      presequence using CD and 2D-HR NMR techniques by determining the structure as a
      function of the concentration of trifluoroethanol. It was found that the
      hydrophobic cluster Ile7-Leu8-Leu9 forms the helix nucleation site, expanding to
      include residues Asn4 to Lys16 when the concentration of trifluoroethanol is
      increased from 10 to 30%. At higher trifluoroethanol concentrations an increased
      'stiffening' of the polypeptide backbone (to Arg26) is observed. In addition, by
      recording CD spectra at different trifluoroethanol concentrations as a function
      of temperature, it was found that the equilibrium constant between helix and
      random coil formation for this peptide exhibits a strong temperature dependence
      with maximum values between 20 and 30 degrees C. Comparison of these equilibrium
      constants with those of homopolymers stressed the unique character of the
      mitochondrial presequence. The findings are discussed in relation to the
      molecular recognition events at different stages of the transport process of this
      protein into mitochondria.

PMID- 10971592
TI  - Photoinduced intracomplex electron transfer between cytochrome c oxidase and TUPS
      modified cytochrome c.
AB  - A novel method for initiating intramolecular electron transfer in cytochrome c
      oxidase is reported. The method is based upon photoreduction of cytochrome c
      labeled with thiouredopyrene-3,6, 8-trisulfonate in complex with cytochrome
      oxidase. The thiouredopyrene-3,6,8-trisulfonate-labeled cytochrome c was prepared
      by incubating the thiol reactive form of the dye with yeast iso-1-cytochrome c,
      containing a single cysteine residue. Laser pulse excitation of a
      stoichiometrical complex between thiouredopyrene-3,6,8-trisulfonate-cytochrome c
      and bovine heart cytochrome oxidase at low ionic strength resulted in the
      reduction of cytochrome c by the excited form of thiouredopyrene-3,6, 8
      trisulfonate and subsequent intramolecular electron transfer from the reduced
      cytochrome c to cytochrome oxidase. The maximum efficiency by a single laser
      pulse resulted in the reduction of approximately 17% of cytochrome a, and was
      achieved only at a 1 : 1 ratio of cytochrome c to cytochrome oxidase. At higher
      cytochrome c to cytochrome oxidase ratios the heme a reduction was strongly
      suppressed.

PMID- 10971593
TI  - Structure of the F420H2:quinone oxidoreductase of Archaeoglobus fulgidus
      identification and overproduction of the F420H2-oxidizing subunit.
AB  - The F420H2:quinone oxidoreductase from the sulfate-reducing archaeon
      Archaeoglobus fulgidus is encoded by the fqo gene cluster which comprises 11
      genes (fqo J, K, M, L, N, A, BC, D, H, I, F). The last gene of the cluster, fqoF,
      was overexpressed in Escherichia coli. The purified subunit was able to oxidize
      reduced cofactor F420 using the electron-acceptor system methyl viologen plus
      metronidazole. The specific activity at 78 degrees C was 64 micromol F420H2
      oxidized. min-1.(mg protein)-1. The purified polypeptide contained 10.6 mol non
      heme iron, 7.2 mol acid-labile sulfur and 0.7 mol FAD per mol protein. With the
      exception of fqoF, the deduced amino-acid sequences of all other genes show
      homologies to distinct subunits of NADH-quinone oxidoreductases from prokaryotes
      and eukaryotes. Thus, it is concluded that the F420H2-dependent and the NADH
      dependent enzyme are functional equivalents. Both proteins are the initial
      enzymes of membrane-bound electron-transport systems and are involved in energy
      conservation. In parallel with bacterial complex I, the F420H2:quinone
      oxidoreductase may be composed of three subcomplexes. FqoF functions as the input
      device adjusted to the oxidation of reduced cofactor F420H2, thereby replacing
      subunits of the input module of complex I that are not present in A. fulgidus.
      The subunits FqoB, FqoCD and FqoI may form the membrane-associated module and
      transfer electrons to the membrane-integral module. It is most likely that the
      last subcomplex is composed of FqoA, FqoH, FqoJ, FqoK, FqoL, FqoM and FqoN. All
      subunits are highly hydrophobic and are probably involved in the reduction of a
      special menaquinone with a fully reduced isoprenoid side chain present in the
      cytoplasmic membrane of A. fulgidus.

PMID- 10971594
TI  - Catalytic reductive dehalogenation of hexachloroethane by molecular variants of
      cytochrome P450cam (CYP101).
AB  - CYP101 (cytochrome P450cam) catalyses the oxidation of camphor but has also been
      shown to catalyse the reductive dehalogenation of hexachloroethane and
      pentachloroethane. This reaction has potential applications in the biodegradation
      of these environmental contaminants. The hexachloroethane dehalogenation activity
      of CYP101 has been investigated by mutagenesis. The effects of active-site
      polarity and volume were probed by combinations of active-site mutations.
      Increasing the active-site hydrophobicity by the Y96A and Y96F mutations
      strengthened hexachloroethane binding but decreased the rate of reaction.
      Increasing the polarity with the F87Y mutation drastically weakened
      hexachloroethane binding but did not affect the rate of reaction. The Y96H
      mutation had little effect at pH 7.4, but weakened hexachloroethane binding while
      increasing the rate of dehalogenation by up to 40% at pH 6.5, suggesting that the
      imidazole side-chain was partially protonated at pH 6.5 but not at pH 7.4.
      Substitutions by bulkier side-chains at F87, T101 and V247 weakened
      hexachloroethane binding but increased the dehalogenation rate. The effect of the
      individual mutations was additive in multiple mutants, and the most active mutant
      for hexachloroethane reductive dehalogenation at pH 7.4 was F87W-V247L (80 min-1
      or 2.5 x the activity of the wild-type). The results suggested that the CYP101
      active site shows good match with hexachloroethane, the Y96 side-chain plays an
      important role in both hexachloroethane binding and dehalogenation, and
      hexachloroethane binding and dehalogenation places conflicting demands on active
      site polarity and compromises were necessary to achieve reasonable values for
      both.

PMID- 10971595
TI  - Recombinant human interferon beta in relapsing-remitting multiple sclerosis: a
      review of the major clinical trials.
AB  - The beneficial effects of interferon beta (IFN-beta) on disease activity in
      relapsing-remitting multiple sclerosis (RRMS) have been confirmed in several
      clinical trials. Three IFN-beta products are currently available and licensed for
      use in RRMS at different dosages and with different routes of administration. For
      the prescribing physician, therefore, questions remain about the effect these
      differences may have on the success of therapy. This paper reviews the four large
      placebo-controlled clinical trials that have been conducted with IFN-beta in
      patients with RRMS. The evidence available indicates that optimal results are
      likely to be achieved with the highest tolerable dosage of IFN-beta. Furthermore,
      as inflammatory brain lesions in MS have been shown to exhibit more extensive and
      early axonal damage than previously suspected, early treatment may be advisable
      in order to delay disease progression in RRMS.

PMID- 10971597
TI  - Statistical maps of cerebral blood flow deficits in Alzheimer's disease.
AB  - Images of cerebral blood flow or metabolism are useful as adjunct to the
      differential diagnosis of cortical dementia. The aim of this study was to create
      statistical objective voxel maps of significant differences in regional cerebral
      blood flow between patients with Alzheimer's disease and age-matched healthy
      volunteers. Maps of significantly reduced cerebral blood flow were created based
      on a spatially normalized distribution of cerebral blood flow, measured with O-15
      water and positron emission tomography in 16 Alzheimer's patients, compared to 16
      healthy age-matched volunteers. After spatial normalization of voxel counts, the
      t-statistic of the cerebral blood flow deficit was determined from the local
      voxel-SDs. In the patients, significant reduction (P < 0.05) of the flow
      distribution was present in regions near the hippocampus, extending rostrally to
      the temporo-parietal region in both hemispheres, including the medial parietal
      cortex plus smaller frontal areas. The maximum reduction occurred in the left
      tapetum/hippocampus (53%, P = 0.061). In conclusion, statistical maps of cerebral
      blood flow deficits objectively reveal the location of deficits, identifying
      areas that are difficult to identify by subjective visual inspection of
      conventional sections of cerebral blood flow maps. This is particularly well
      illustrated by the pronounced flow reduction of the medial parietal cortices.

PMID- 10971596
TI  - Problems associated with switch to modafinil - a novel alerting agent in
      narcolepsy.
AB  - Modafinil is a novel medication recently approved for the treatment of narcolepsy
      and idiopathic hypersomnia. Commonly, patients had already been prescribed
      medications for their syndrome. This report outlines difficulties encountered in
      the clinical practice of switching patients to modafinil. Naive subjects accepted
      modafinil best. Subjects withdrawn from amphetamine had the most problems and
      failure to withdraw. Venlafaxine hydrochloride combined well with modafinil to
      control cataplectic attacks. Usage of a progressive withdrawal protocol may ease
      the difficulties observed.

PMID- 10971598
TI  - Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy:
      comparison with coregistered hippocampal metabolism and volumetry.
AB  - The significance of benzodiazepine receptor (BZR) concentration in comparison
      with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed
      with temporal lobe epilepsy (TLE) without hippocampal signal change on T2
      weighted magnetic resonance imaging (MRI) scans. Focus lateralization was
      achieved by clinical, electroencephalographic and neuropsychological
      examinations. Three-dimensional positron emission tomography (PET) and MRI scans
      were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding,
      normalized to average cortical values for glucose metabolism (rCMRglc) and
      volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of
      interest (VOI) were used for calculation of asymmetries between clinically
      affected and unaffected sides. Eleven out of 14 TLE patients presented a
      significant reduction in hippocampal volume. In nine of these 11 patients
      hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced.
      In two patients without hippocampal volume asymmetry FMZ binding was markedly
      reduced in the mesial temporal lobe appropriately to the clinically diagnosed
      side. In our study volumetry is therefore the most sensitive tool for the
      detection of hippocampal abnormality in TLE. However, in cases without
      hippocampal atrophy the reduction of FMZ may indicate functional impairment of
      BZR before neuronal loss becomes evident. Our results emphasize the complementary
      nature of these tests in TLE patients.

PMID- 10971599
TI  - Effect of diabetes on some primitive reflexes.
AB  - Primitive reflexes (PRs) are present in newborns; they disappear as the brain
      matures and increase in frequency in healthy elderly individuals. Primitive
      reflexes are more frequent in some neurological disorders than in age-matched
      controls. The aim of this study was to investigate the effect of diabetes on some
      PRs. We examined three PRs (glabellar tap, snout and palmomental reflexes) in 376
      subjects: 111 normal age-matched controls, 60 patients with cerebrovascular
      disease (CVD) and 205 patients with type 2 diabetes mellitus. The latter patients
      were divided into three groups: (1) diabetics without neurological complications
      (D); (2) diabetics with cerebrovascular disease (D-CVD); and (3) diabetics with
      polyneuropathy (D-PN). The frequency of PRs was increased in CVD, unchanged in D
      CVD (except palmomental) and greatly reduced in D and D-PN. It is possible that
      the vascular lesions in perforating arteries of the pons in diabetic subjects,
      previously studied in some pathological reports, can account for the reduced
      occurrence of primitive reflex responses.

PMID- 10971600
TI  - Glyceryl trinitrate induced headache in migraineurs - relation to attack
      frequency.
AB  - Glyceryl trinitrate, a prodrug of nitric oxide, induces a mild to moderate
      headache in healthy subjects, whilst migraineurs develop a more severe headache,
      resembling spontaneous migraine attacks. In order to investigate whether this
      increased nitric oxide sensitivity depends upon the frequency of spontaneously
      occurring migraine attacks, intravenous infusion of glyceryl trinitrate (0.5
      microg/kg/min) was given to 15 migraine patients with rare attacks (</=4
      attacks/year) of migraine without aura. Fourteen age-matched migraine patients
      with frequent attacks of migraine without aura (>/=12 attacks/year) and 14
      healthy subjects served as controls. No significant difference between the
      migraine groups for any of several parameters was detected, although the trend
      was always towards more headaches in frequent migraineurs. Both migraineurs with
      frequent and rare attacks experienced a headache that was significantly more
      severe, longer lasting, and fulfilled the diagnostic criteria for migraine
      without aura more often, compared to the healthy subjects (P = 0.0001).
      Conclusively, supersensitivity to glyceryl trinitrate in migraineurs seems to be
      related to a basic - probably genetically determined - pathophysiological
      mechanism involving nitric oxide, and not to the environmental influences, which
      to a large extent determine the expression of migraine.

PMID- 10971601
TI  - Weekday distribution of alcohol consumption in Norway: influence on the
      occurrence of epileptic seizures and stroke?
AB  - Binge drinking at weekends is considered to be a predominant feature of alcohol
      consumption in the Nordic countries. Neurological diseases, such as seizures and
      stroke, have been reported to occur in temporal relation to alcohol intoxication
      and withdrawal. We wanted to investigate weekday variances in alcohol consumption
      in relation to the onset of neurological symptoms in these disorders. Consecutive
      patients admitted for epileptic seizures (n = 142) and ischemic strokes (n = 91)
      were included in the study. Control groups were consecutively hospitalized
      sciatica patients (n = 181), outpatients with epilepsy (n = 91), and healthy
      subjects (n = 254). The day-by-day alcohol intake during the 8 days prior to
      hospital admission was recorded. Seizures occurring in subjects with hazardous
      alcohol consumption, operationally defined by a score > or =8 in the Alcohol Use
      Disorders Identification Test (AUDIT-positive) were considered to be related to
      alcohol use. Binge drinkers were identified by an alcohol intake, on at least 1
      of the last 3 days, of > or =6 standard units in men, or > or =4 standard units
      in women. Thirty-five percent of seizure patients were AUDIT-positive, in
      contrast to 18% and 16% of stroke and sciatica patients, and 12% and 13% of
      epilepsy outpatients and healthy controls. Twenty-three percent of seizure
      patients were binge drinkers whereas in the other groups, this proportion did not
      exceed 10%. In all groups, alcohol consumption peaked on Saturdays. More seizures
      occurred on Mondays compared to Saturdays, with a diminishing trend through the
      week. However, AUDIT-negative seizure patients, of which binge drinking occurred
      in only 5%, caused this difference. AUDIT-positive seizure patients had a higher
      and more evenly distributed alcohol intake through the week, and the occurrence
      of seizures in this group did not differ significantly between days of the week.
      Alcohol consumption peaked 2 days prior to the onset of withdrawal seizures. The
      weekend drinking pattern was confirmed for all the study groups. Hazardous
      alcohol consumption preceded every third acute seizure, but was found in only one
      of eight outpatients with epilepsy. AUDIT-negative patients caused a peak of
      seizure admissions on Mondays, compared to Saturdays, with a diminishing trend
      through the week.

PMID- 10971602
TI  - Randomized controlled trial of brain-derived neurotrophic factor in Guillain
      Barre syndrome: a pilot study.
AB  - Brain-derived neurotrophic factor (BDNF) has the theoretical potential to protect
      neurones from axonal degeneration. The objective of this study was to discover
      whether brain-derived neurotrophic factor is safe in Guillain-Barre syndrome, and
      to make preliminary observations of its efficacy. This was a parallel group
      randomized controlled trial of subcutaneous brain-derived neurotrophic factor 25
      microg/kg daily compared with placebo for up to 24 weeks or until patients could
      walk without aid. Six patients received brain-derived neurotrophic factor, of
      whom three had serious adverse events including one death. Four patients received
      placebo, of whom two had serious adverse events including one death. The rate and
      extent of recovery were similar in the two groups. This pilot study did not
      detect any serious adverse events attributed to brain-derived neurotrophic factor
      treatment.

PMID- 10971603
TI  - The application of control limits analysis to the myometric assessment of motor
      performance in neuropathy patients.
AB  - Measurement of muscle strength by myometry is used to monitor the natural course
      and treatment response of motor system diseases, both in individual patients and
      clinical trials. However, the practical usefulness of myometric data is reliant
      upon a statistical method for analysing serial strength measurements which
      distinguishes disease-related changes from random fluctuations in patient
      performance and operator/device dependent measurement errors. In this study we
      have applied control limits analysis to this problem. Using hand-held
      dynamometry, sets of baseline strength measurements were collected on two
      separate occasions during a period of clinical stability from up to four muscle
      groups in 22 patients with peripheral neuropathies. From these sets of data, 76
      control limits were calculated and then used to describe the inter-measurement
      variation in muscle strength in individual muscles. The range of control limits
      was wide, varying from <10% of baseline (in 36% of muscles tested) to >50% (in 4%
      of muscles tested), with 88% of muscles falling within 30% of baseline. Follow-up
      data were also collected from all patients, including those undergoing treatment.
      Control limits analysis is a powerful and simple method for assessing the
      significance of motor performance changes in individual muscles in patients
      undergoing serial monitoring and can be easily applied to both single patients
      and clinical trials.

PMID- 10971604
TI  - Chlamydia pneumoniae-associated ADEM.
AB  - Inflammatory demyelinating diseases are a common cause of neurologic disability
      in young adults, and usually the cause is unknown. We describe a case of acute
      disseminated encephalomyelitis (ADEM) associated with Chlamydia pneumoniae
      infection. An 18-year-old previously healthy women, with a one-week history of
      coryzal illness, was admitted because of progressive headache, dizziness, and a
      left-sided hemiparesis. MR imaging of the brain and brainstem showed typical
      signs of ADEM. The diagnosis was established by PCR Chlamydia pneumoniae DNA
      positivity in a tracheal swab and by increasing titres of Chlamydia IgM antibody.
      The patient was treated with doxycycline and steroids and recovered completely.
      Apart from therapeutic implications, this case may contribute to our
      understanding of demyelinating diseases of the central nervous system.

PMID- 10971605
TI  - Malignant pheochromocytoma with progressive paraparesis in von Hippel-Lindau
      disease.
AB  - Pheochromocytomas are a feature of the von Hippel-Lindau disease spectrum, a
      multisystem disorder of autosomal dominant inheritance. Pheochromocytomas are,
      however, observed during life with a lower frequency than other features of this
      disease, such as retinal angiomas, haemangioblastomas of the CNS, and renal
      carcinomas. We present the highly unusual case of a patient who required an
      emergency operation for an intradural extramedullary thoracic tumour which was
      clinically suggestive initially of neurinoma. We present evidence from NMR,
      histological and isotope scan investigations of this being a pheochromocytoma
      metastasis and of an additional right-sided paraganglioma at the same height. A
      detailed history revealed that this patient had suffered from four other
      pheochromocytomas and two other paragangliomas, in addition to retinal
      angiomatosis of von Hippel-Lindau disease. This case is extraordinary due to (i)
      the unusual site of the metastasis, (ii) the neurological requirement for an
      emergency operation of pheochromocytoma, (iii) metastasis of pheochromocytoma in
      von Hippel-Lindau disease (only eight previous cases), and (iv) the number of
      recurrent pheochromocytomas. It clearly demonstrates the necessity for frequent
      and life-long follow-up in von Hippel-Lindau disease.

PMID- 10971606
TI  - Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins
      lymphoma.
AB  - A 57-year-old female in complete remission of grade IV non-Hodgkin lymphoma
      whilst on intensive chemotherapy, suddenly developed unilateral hemispheric
      stroke with a fatal outcome in 3 days. She was apyrexial and had received
      antifungal prophylaxis during her treatment. Post-mortem examination showed
      complete thrombosis of the internal carotid artery leading to infarction in the
      territory of the middle and anterior cerebral arteries. Microscopic examination
      of the brain showed involvement of intra-cranial vessel walls and brain
      parenchyma by mucormyces, with no evidence of systemic mucormycosis. Isolated
      cerebral mucormycosis is a rare occurrence, more commonly found in intravenous
      drug abusers, but can occur in patients with haematological malignancy.

PMID- 10971607
TI  - Mitral papillary fibroelastoma as a cause of cardiogenic embolic stroke: report
      of two cases and review of the literature.
AB  - Papillary fibroelastoma (PFE) is a rare benign tumour that attaches to the
      endocardial surface, mostly on cardiac valves. Though usually asymptomatic, it
      can be the source of several complications. To date, 49 cases have been reported
      of embolic stroke with a PFE as the probable origin. CASE REPORTS: (i) a 39-year
      old male presented with ischemic embolic stroke; the presence of a PFE was
      assessed by means of transoesophageal echocardiography and confirmed by
      pathological findings; (ii) a 32-year-old woman presented with sudden onset of
      left hemiparesis; a cardiogenic embolic stroke was suspected, and a diagnosis of
      PFE was made based on echocardiographic and pathological findings. In both cases,
      surgical excision of the tumours was performed with no recurrences at follow-up.
      Two mechanisms can explain the formation of emboli in PFE: dislodgement of the
      tumour leaves or fibrin-platelet aggregation on the endocardial surface of these
      leaves. Transthoracic echocardiography may lead to the suspicion of a PFE, but
      transoesophageal echocardiography is required for confirmation. Prompt surgical
      excision is indicated in most cases. Anticoagulation is only recommended in
      situations of high surgical risk and during the wait for surgery.

PMID- 10971608
TI  - Opsoclonus-myoclonus syndrome: gabapentin as a new therapeutic proposal.

PMID- 10971609
TI  - Synaptic stimulation of nicotinic receptors in rat sympathetic ganglia is
      followed by slow activation of postsynaptic potassium or chloride conductances.
AB  - Two slow currents have been described in rat sympathetic neurons during and after
      tetanization of the whole preganglionic input. Both effects are mediated by
      nicotinic receptors activated by native acetylcholine (ACh). A first current,
      indicated as IAHPsyn, is calcium dependent and voltage independent, and is
      consistent with an IAHP-type potassium current sustained by calcium ions
      accompanying the nicotinic synaptic current. The conductance activated by a
      standard synaptic train was approximately 3.6 nS per neuron; it was detected in
      isolation in 14 out of a 52-neuron sample. A novel current, IADPsyn, was
      described in 42/52 of the sample as a post-tetanic inward current, which
      increased in amplitude with increasing membrane potential negativity and
      exhibited a null-point close to the holding potential and the cell momentary
      chloride equilibrium potential. IADPsyn developed during synaptic stimulation and
      decayed thereafter according to a single exponential (mean tau = 148.5 ms) in 18
      neurons or according to a two-exponential time course (tau = 51.8 and 364.9 ms,
      respectively) in 19 different neurons. The mean peak conductance activated was
      approximately 20 nS per neuron. IADPsyn was calcium independent, it was affected
      by internal and external chloride concentration, but was insensitive to specific
      blockers (anthracene-9-carboxylic acid, 9AC) of the chloride channels open in the
      resting neuron. It is suggested that gADPsyn represents a specific chloride
      conductance activatable by intense nicotinic stimulation; in some neurons it is
      even associated with single excitatory postsynaptic potentials (EPSCs). Both IAHP
      and IADPsyn are apparently devoted to reduce neuronal excitability during and
      after intense synaptic stimulation.

PMID- 10971610
TI  - Synaptically released 5-HT modulates the activity of tonically discharging
      neuronal populations in the rostral ventral medulla (RVM).
AB  - There is substantial evidence for an important modulating role of monoamines
      (catecholamines and serotonin, 5-HT) in the rostral ventral medulla (RVM), a
      region which plays an important role in cardiovascular and nociceptive functions.
      We investigated in slices the role of endogenous monoamines in the synaptic
      control of the activity of rat RVM neuronal populations using intracellular
      recordings in the lateral RVM plus lateral aspect of nucleus
      paragigantocellularis lateralis. A triple-labelling protocol allowed us to
      identify the location of impaled neurons and their eventual monoaminergic
      phenotype within the serotonergic and catecholaminergic populations of the RVM.
      Focal electrical stimulation revealed the existence of a functional monoaminergic
      input onto RVM neurons which was mediated by endogenous 5-HT acting at inhibitory
      5-HT1A receptors but did not involve noradrenergic neurotransmission. The slow 5
      HT-mediated inhibitory postsynaptic potential (IPSP) was only observed in the
      regularly discharging neurons, which were found to be neither catecholaminergic
      nor serotonergic. The synaptic release of 5-HT was, itself, under an inhibitory
      control involving GABAA (gamma-aminobutyric acid) receptors. Moreover, we
      characterized the effect of the 5-HT-releasing agent fenfluramine on this
      functional 5-HT-mediated synaptic transmission. Our results show that the effect
      of fenfluramine is biphasic consisting of an initial prolongation of the
      serotonergic IPSP followed by a decrease in amplitude. Our data provide a basis
      for the previously reported inhibitory effects of exogenously applied serotonin
      agonists/antagonists on the autonomic functions controlled by the RVM. This 5-HT
      pathway, which functionally links the serotonergic and catecholaminergic regions,
      might play an important role in cardiovascular and nociceptive functions.

PMID- 10971611
TI  - Identification of an opioid peptide secreted by rat embryonic mixed brain cells
      as a promoter of macrophage migration.
AB  - Conditioned media from embryonic mixed cells from the rat brain were used in a
      chemotaxis assay to look for potential chemotactic activity which could account
      for the infiltration of the developing central nervous system (CNS) by macrophage
      precursors. The most potent chemotactic activity was found in the conditioned
      medium from E17 mixed brain cells (E17-CM). Based upon checkerboard analysis,
      this activity was shown to be chemotactic rather than chemokinetic. This
      chemoattraction was not restricted to brain macrophages (BM) because it was as
      pronounced on bone marrow-derived macrophages. The implication of a peptide
      compound in this activity was suggested by its resistance to heat as well as acid
      treatments, and by its sensitivity to aminopeptidase M digestion. In agreement
      with the opioid nature of the peptide, not only naloxone, but also the delta
      opioid receptor antagonist ICI-174 reduced the migration of BM in response to E17
      CM by 60%. This migratory activity was no longer effective when pertussis toxin
      treated BM were used. When the chemotactic effects of selective opioid agonists
      were compared to that of E17-CM, DPDPE, the delta agonist, was the most efficient
      in attracting BM. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis indicated that delta as well as other known opioid receptors were
      expressed in both BM and E17 mixed brain cells. Finally, a Met-enkephalin-like
      reactivity was found by RIA in the E17-CM. Altogether, these observations suggest
      that a delta-like opioid peptide released from embryonic mixed brain cells could
      be responsible for the infiltration of the developing CNS by macrophages
      precursors.

PMID- 10971612
TI  - Single-cell mRNA expression of HCN1 correlates with a fast gating phenotype of
      hyperpolarization-activated cyclic nucleotide-gated ion channels (Ih) in central
      neurons.
AB  - Hyperpolarization-activated currents (Ih) are key players in shaping rhythmic
      neuronal activity. Although candidate genes for Ih channels have been cloned
      (HCN1-HCN4), the subunit composition of different native Ih channels is unknown.
      We used a combined patch-clamp and qualitative single-cell reverse transcription
      multiplex polymerase chain reaction (RT-mPCR) approach to analyse HCN1-4
      coexpression profiles in four neuronal populations in mouse CNS. Coexpression of
      HCN2, HCN3 and HCN4 mRNA was detected in single neurons of all four neuronal cell
      types analysed. In contrast, HCN1 mRNA was detected in neocortical and
      hippocampal pyramidal neurons but not in dopaminergic midbrain and
      thalamocortical neurons. HCN1 expression was correlated with significantly faster
      activation kinetics on the level of individual neurons. Semiquantitative single
      cell RT-mPCR analysis demonstrated that HCN1 mRNA expression is at least
      eightfold higher in cortical neurons than subcortical neurons. We show that
      single neurons possess complex coexpression patterns of Ih candidate genes.
      Alternative expression of HCN1 is likely to be an important molecular determinant
      to generate the different neuronal Ih channel species adapted to tune either
      subcortical or cortical network activity.

PMID- 10971613
TI  - Regulation of NGF-family ligands and receptors in adulthood and senescence:
      correlation to degenerative and regenerative changes in cutaneous innervation.
AB  - During development, a highly differential neurotrophin dependency is reported for
      various types of nerve endings in the whisker follicle. To what extent these
      dependencies extend and play a role in adulthood is largely unresolved. We show
      here, using in situ hybridization and immunohistochemistry that the expression of
      neurotrophins and trk/p75 receptors persists in adulthood. As suggested by their
      expression profiles, many classes of cutaneous nerve endings disclose similar
      ligand-receptor dependencies in adult animals as during development, while other
      populations appear to switch their dependency. Furthermore, our data suggest that
      sensory endings that have a high turnover due to mechanical wear and tear, e. g.
      Merkel cell-neurite complexes at the level of ring sinus show a more complex
      ligand-receptor expression phenotype than do endings with a less vulnerable
      location, e.g. the Merkel cell-neurite complexes at the rete ridge collar. Thus,
      neurotrophin-3 (NT3)/trkA signalling is suggested to be important for a
      continuous terminal plasticity of Merkel cell-neurite complexes at the level of
      ring sinus in adulthood. Evidence supporting a role for neurotrophin signalling
      in maintaining the adult cutaneous innervation also comes from the close
      correlation between altered ligand-receptor expression(s) and axonal/terminal
      aberrations in senescence. Thus, an ageing-related decrease in target
      neurotrophin expression, notably NT3 and NT4, results in a site-specific loss of
      sensory terminals concomitant with an aberrant growth of regenerating/sprouting
      axons into new target fields. Ageing of the cutaneous innervation, manifested in
      degenerative and regenerative events, seems strongly associated with changes in
      neurotrophic interactions between sensory neurons and target tissues.

PMID- 10971614
TI  - Aberrant trajectory of entorhino-dentate axons in the mutant Shaking Rat
      Kawasaki: a Dil-labelling study.
AB  - The Shaking Rat Kawasaki (SRK) is a neurological mutant that exhibits
      abnormalities of cell migration and lamination, with many similarities to the
      mouse reeler mutant. We recently used lamina-specific antibody staining to show
      that despite severe aberrations in the laminar organization of the SRK dentate
      gyrus, the entorhinal terminal field in the outer dentate molecular layer
      appeared relatively normal (Woodhams & Terashima, 1999, J. Comp. Neurol. 409
      p57). However, neurofilament immunostaining suggested that entorhino-dentate
      afferents take an abnormal trajectory in reaching their appropriate targets, the
      granule cells dendrites. In the present study, anterograde tracing with the
      carbocyanine dye 1, 1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate (DiI) has been used to delineate directly the path that entorhinal
      axons take to the dentate gyrus, confirming that in SRK entorhinal axons do
      indeed reach their appropriate terminal fields in the molecular layer, with
      laminar segregation between projections from the lateral and medial entorhinal
      cortices. However, these fibres fail to cross the hippocampal fissure between the
      subiculum and the dentate gyrus, coursing instead parallel to it until they curve
      round the deepest point of the fissure in field CA3. Similar findings were seen
      in the murine reeler mutant. Insertion of DiI crystals into the entorhinal cortex
      of neonatal rats also retrogradely labelled the developmentally transient Cajal
      Retzius cells at the hippocampal fissure; these survive for longer in SRK than in
      normal littermates. The presence of a marked astrogliosis at the SRK hippocampal
      fissure may play a part in determining the abnormal trajectory taken by entorhino
      dentate afferents in this mutant.

PMID- 10971615
TI  - Programmed cell death in the developing human telencephalon.
AB  - Programmed cell death (PCD) in the form of apoptosis is recognized as one of the
      central events in the development of the central nervous system. To study the
      time of onset, extent and distribution of PCD in the human telencephalon, embryos
      and fetuses from 4.5 to 27 gestational weeks (g.w.) were examined using the TUNEL
      (TdT-mediated dUTP-biotin nick-end labelling) in situ method. At 4.5 g.w. sparse
      TUNEL(+) nuclei were observed in the ventricular zone of the neural tube. With
      the formation of the cortical plate at 7-8 g.w. , TUNEL(+) nuclei were seen in
      all developmental layers of the cortical anlage, as well as in the subcortical
      regions such as the ganglionic eminence and the internal capsule. The
      proliferative zones (the ventricular zone, the subventricular zone and the
      ganglionic eminence) contained the majority of all apoptotic nuclei observed in
      each specimen. However, the apoptotic index was highest in the subplate zone and
      in layer I. Double-labelling experiments suggested that neuronal precursors were
      the main population of cells undergoing PCD in the first trimester of gestation,
      whereas glial cells probably start dying around midgestation. The onset of
      labelling of microglial cells and apoptotic nuclei were synchronous, indicating
      the involvement of microglia in PCD. In conclusion, two distinct types of PCD
      were observed during human telencephalic development: embryonic apoptosis, which
      was synchronous with proliferation and migration of neuronal cells and probably
      not related to establishment of neuronal circuitry, and fetal apoptosis, which
      coincided with differentiation and synaptogenesis, and therefore may be related
      to the development of axonal-target connectivity.

PMID- 10971616
TI  - beta-amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic
      cascade in rat nucleus basalis.
AB  - Whereas a cardinal role for beta-amyloid protein (Abeta) has been postulated as a
      major trigger of neuronal injury in Alzheimer's disease, the pathogenic mechanism
      by which Abeta deranges nerve cells remains largely elusive. Here we report
      correlative in vitro and in vivo evidence that an excitotoxic cascade mediates
      Abeta neurotoxicity in the rat magnocellular nucleus basalis (MBN). In vitro
      application of Abeta to astrocytes elicits rapid depolarization of astroglial
      membranes with a concomitant inhibition of glutamate uptake. In vivo Abeta
      infusion by way of microdialysis in the MBN revealed peak extracellular
      concentrations of excitatory amino acid neurotransmitters within 20-30 min. Abeta
      triggered extracellular elevation of excitatory amino acids coincided with a
      significantly enhanced intracellular accumulation of Ca2+ in the Abeta injection
      area, as was demonstrated by 45Ca2+ autoradiography. In consequence of these
      acute processes delayed cell death in the MBN and persistent loss of cholinergic
      fibre projections to the neocortex appear as early as 3 days following the Abeta
      induced toxic insult. Such a sequence of Abeta toxicity was effectively
      antagonized by the N-methyl-D-aspartate (NMDA) receptor ligand dizocilpine
      maleate (MK-801). Moreover, Abeta toxicity in the MBN decreases with advancing
      age that may be associated with the age-related loss of NMDA receptor expression
      in rats. In summary, the present results indicate that Abeta compromises neurons
      of the rat MBN via an excitotoxic pathway including astroglial depolarization,
      extracellular glutamate accumulation, NMDA receptor activation and an
      intracellular Ca2+ overload leading to cell death.

PMID- 10971617
TI  - Regulation of the biosynthesis and processing of chromogranins in organotypic
      slices: influence of depolarization, forskolin and differentiating factors.
AB  - Slices from rat hippocampus in organotypic culture were used to study the
      biosynthesis regulation of chromogranins A and B and secretogranin II.
      Additionally, we investigated the proteolytic conversion of secretogranin II and
      the levels of prohormone convertases putatively involved. Forskolin treatment and
      depolarization with potassium plus BayK 8644 led to significant increases in
      secretogranin II mRNA in the principal cells of the hippocampus. Enhanced
      expression of secretogranin II was also reflected by a rise in peptide levels.
      Despite this induction of biosynthesis the extensive processing to secretoneurin
      normally observed in brain was maintained. Both forskolin and depolarization
      upregulated the prohormone convertase (PC)1, but not PC2, indicating that PC1
      levels are critical for secretoneurin production under stimulating conditions.
      Results obtained for chromogranins A and B were less consistent. For chromogranin
      A mRNA, changes were restricted to granule cells; for chromogranin B, a response
      in granule cells was observed to depolarization but not to forskolin, and effects
      in pyramidal neurons were weak. Accordingly, we were unable to detect alterations
      in chromogranin A and B protein levels. Furthermore, we tested several
      neurotrophic growth factors and found that only basic fibroblast growth factor
      raised secretogranin II expression without affecting chromogranins A and B. The
      hippocampal slice preparation allowed well controlled treatment with
      identification of neuronal subpopulations and yielded data largely matching
      experiments in vivo and in cell culture. The pronounced regulation of
      secretogranin II and its effective processing underlines the importance of the
      resulting peptide secretoneurin as an active neuropeptide in the nervous system.

PMID- 10971618
TI  - Generation and propagation of 4-AP-induced epileptiform activity in neonatal
      intact limbic structures in vitro.
AB  - We examined the generation, propagation and pharmacology of 4-aminopyridine (4
      AP)-induced epileptiform activity (EA) in the intact interconnected limbic
      structure of the newborn (P0-7) rat in vitro. Whole-cell recordings of CA3
      pyramidal cells and multisite field potential recordings in CA3, CA1, dentate
      gyrus, and lateral and medial entorhinal cortex revealed 4-AP-induced EA as early
      as P0-1. At this age, EA was initiated in the CA3 region and propagated to CA1,
      but not to the entorhinal cortex. Starting from P3-4, EA propagated from CA3 to
      the entorhinal cortex. Along the CA3 septo-temporal axis, EA arose predominantly
      from the septal pole and spread towards the temporal site. Whereas the onset of 4
      AP-induced EA decreased with age from 21.2 +/- 1.6 min at P0-1 to 4.7 +/- 0.63
      min at P6-7, the seizure duration increased in the same age groups from 98 +/- 14
      s to 269.4 +/- 85.9 s, respectively. The EA was blocked by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) but not by DL-2-amino-5-phosphonovaleric acid
      (APV), (+)-MK-801 hydrogen maleate (MK-801) or (+/-)-alpha-methyl-4
      carboxyphenylglycine (MCPG), suggesting that they were mediated by alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor activation. We
      conclude that: (i) the septal pole of the hippocampal CA3 region plays a central
      role in the generation of EA in the neonatal limbic system; and (ii) AMPA/kainate
      receptor-mediated EA can be generated in CA3 already at birth. Therefore, the
      recurrent collateral synapses and circuits required for the generation of EA are
      developed earlier than previously suggested on the basis of studies on
      hippocampal slices.

PMID- 10971619
TI  - Basal forebrain nitric oxide synthase (NOS)-containing neurons project to
      microvessels and NOS neurons in the rat neocortex: cellular basis for cortical
      blood flow regulation.
AB  - Stimulation of basal forebrain neurons results in local increases in cortical
      cerebral blood flow that are dependent upon cholinergic and nitrergic mechanisms.
      In the present study, we investigated the possibility that basal forebrain nitric
      oxide synthase (NOS)-containing neurons project to microvessels and NOS
      interneurons in the rat cerebral cortex. We performed quisqualic (QUIS) acid
      lesions of the basal forebrain and evaluated their effects on cortical NOS
      immunostained nerve terminals, with emphasis on those associated with
      microvessels and NOS interneurons, both at the light and/or electron microscopic
      levels. The results show that basal forebrain NOS neurons provide about one third
      of the overall cortical NOS innervation. Further, the data indicate that
      basalocortical NOS fibres establish privileged associations with microvessels and
      NOS neurons, as respective denervations of 60 and 45% were observed following
      lesion. At the electron microscopic level, most perivascular NOS neuronal
      elements corresponded to nerve terminals and a majority ( approximately 25%) of
      these were located in the immediate vicinity of the blood vessels, similar to the
      perivascular distribution reported previously for classic
      neurotransmitters/neuromediators. NOS terminals abutting on cortical NOS neurons
      were primarily nonjunctional. Altogether, these results raise the possibility
      that not only cholinergic but also nitrergic basal forebrain neurons are involved
      in the flow response observed following stimulation of the basal forebrain.
      Further, they suggest interactions between basalocortical and intracortical NOS
      neurons. We conclude that these interactions are involved in the spatial and
      temporal regulation of cortical perfusion following basal forebrain activation,
      and that they may become dysfunctional in pathologies such as Alzheimer's disease
      which affects both the basal forebrain and the cortical NOS neurons.

PMID- 10971620
TI  - Afferent ingrowth and onset of activity in the rat trigeminal nucleus.
AB  - A novel in vitro preparation, consisting of the rat brainstem with the trigeminal
      ganglion attached, has been used to study the anatomical and functional
      development of the trigeminal nucleus from embryonic day (E)13 to postnatal day
      (P)6. Neurobiotin injections into the trigeminal ganglion showed that primary
      afferents had reached the trigeminal tract by E13 and had grown simple, mainly
      unbranched, collaterals into all levels of the nucleus by E15. By E17, these
      collaterals were extensively branched, with occasional boutons present. Patches
      of intense neurobiotin-labelled terminals, corresponding to whisker-related
      patterns, were first seen at E20 and became clearer over the next few days.
      Terminal arbours at this stage were relatively localized and densely branched,
      with many boutons. Responses from the trigeminal nucleus were recorded with
      suction electrodes, following stimulation of the trigeminal ganglion. Recordings
      from the main sensory nucleus showed a postsynaptic response was first present at
      E15. At E16, bath application of AP5 and DNQX showed that the response contained
      both NMDA and AMPA components, with NMDA predominating (75%). The NMDA : AMPA
      ratio remained high until P1, then gradually declined to 50% by P6. The
      postsynaptic response was also reduced by bath application of bicuculline,
      indicating the presence of a GABAA-mediated excitatory component. GABAergic
      excitation was present at all ages but was maximal from E20 to P1, the age at
      which whisker-related patterns are developing. It is hypothesized that both
      GABAergic excitation and NMDA receptor activation play a role in the
      consolidation of trigeminal connections, and are thus important in the
      development of whisker-related patterns.

PMID- 10971621
TI  - Spatio-temporal distribution of cellular retinoid binding protein gene
      transcripts in the developing and the adult cochlea. Morphological and functional
      consequences in CRABP- and CRBPI-null mutant mice.
AB  - The expression patterns of the mouse cellular retinoid binding protein genes were
      investigated by in situ hybridization analysis in the inner ear from 10.5 days
      post coitum (dpc) up to the adult stage. The cellular retinoic acid binding
      protein II (CRABPII) and cellular retinol binding protein I (CRBPI) were present
      in a widespread and abundant pattern in cochlear structures during embryogenesis.
      Expression of the cellular retinoic acid binding protein I (CRABPI) is restricted
      during development in Kolliker's organ whilst cellular retinol binding protein II
      (CRBPII) is only visible after birth with a ubiquitous distribution in most
      regions of the cochlea including nervous components. No CRABP or CRBP transcripts
      were observed in the auditory receptors. Morphological observations of CRBPI- and
      CRABPI/CRABPII-null mutant fetus at 18.5 dpc do not show any structural
      modification at the level of the organ of Corti. Furthermore,
      electrophysiological tests performed by measuring distorsion-product otoacoustic
      emissions and auditory brainstem evoked responses did not present significant
      alteration of the auditory function for the different types of mutants. The
      expression of retinoid binding proteins in cochlear structures during
      embryogenesis could suggest important roles for these proteins during ontogenesis
      and morphogenesis of the inner ear. Despite these observations, morphological and
      functional data from mutant mice did not present obvious modifications of the
      cochlear structures and auditory thresholds. It is therefore unlikely that CRABPs
      and CRBPI are directly involved in development of the cochlea and hair cell
      differentiation.

PMID- 10971622
TI  - Basic properties of an inositol 1,4,5-trisphosphate-gated channel in carp
      olfactory cilia.
AB  - In addition to the activation of cAMP-dependent pathways, odorant binding to its
      receptor can lead to inositol 1,4,5-trisphosphate (InsP3) production that may
      induce the opening of plasma membrane channels. We therefore investigated the
      presence and nature of such channels in carp olfactory cilia. Functional analysis
      was performed by reconstitution of the olfactory cilia in planar lipid bilayers
      (tip-dip method). In the presence of InsP3 (10 microM) and Ca2+ (100 nM), a
      current of 1.6 +/- 0.1 pA (mean +/- SEM, n = 4) was measured, using Ba2+ as
      charge carrier. The I/V curve displayed a slope conductance of 45 +/- 5 pS and a
      reversal potential of -29 mV indicating a higher selectivity for divalent
      cations. This current was characterized by two mean open times (3.0 +/- 0.4 ms
      and 42.0 +/- 2.6 ms, n = 4) and was strongly inhibited by ruthenium red (30
      microM) or heparin (10 microg/mL). Importantly, the channel activity was closely
      dependent on the Ca2+ concentration, with the highest open probability (Po) at
      100 nM Ca2+ (Po = 0.50 +/- 0.02, n = 4). Po is lower at both higher and lower
      Ca2+ concentrations. A structural identification of the channel was attempted by
      using a large panel of antibodies, raised against several InsP3 receptor
      (InsP3R)/Ca2+ release channel isoforms. The type 1 InsP3R was detected in carp
      cerebellum and whole brain, while a lower molecular mass InsP3R, which may
      correspond to type 2 or 3, was detected in heart, whole brain and the soma of the
      olfactory neurons. None of the antibodies, however, cross-reacted with olfactory
      cilia. Taken together, these results indicate that in carp olfactory cilia an
      InsP3-dependent channel is present, distinct from the classical InsP3Rs localized
      on intracellular membranes.

PMID- 10971623
TI  - A high GluR1 : GluR2 expression ratio is correlated with expression of Ca2+
      binding proteins in rat forebrain neurons.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazle propionic acid (AMPA) receptors are
      ubiquitously expressed; however, their subtypes and abundance vary from region to
      region. We classified the neurons in various forebrain regions (hippocampus,
      striatum, amygdala, piriform cortex and somatosensory cortex) into six types:
      [R1+/R2+], [R1-/R2+], [R1+/R2-], [R1-/R2-], [R1++/R2+] and [R1++/R2-], and
      analysed the expression of Ca2+-binding proteins, such as parvalbumin and
      calbindin-D28k, using a triple-staining method. The neurons showing a high GluR1
      : GluR2 expression ratio, [R1+/R2-], [R1++/R2+] and [R1++/R2-] neurons, comprised
      13-30% of the total neuronal population. In addition, the expression of Ca2+
      binding proteins was mainly observed in these three types of neurons. The results
      suggest that Ca2+-binding protein-positive neurons express Ca2+-permeable AMPA
      receptors, because the Ca2+-permeability of AMPA receptors is enhanced by the
      relative scarcity of the GluR2 subunit. To directly test the possibility that
      Ca2+-binding protein-positive neurons express Ca2+-permeable AMPA receptors, we
      performed Ca2+-imaging experiments in cultured cortical neurons. Ca2+ influx
      through AMPA receptors was measured selectively by addition of AMPA together with
      cyclothiazide in the presence of blockers of other Ca2+ influx routes. More than
      half of the calbindin-D28k-positive neurons showed a large increase in the
      intracellular Ca2+ concentration ([Ca2+]i), whilst most of the calbindin-D28k
      undetectable neurons exhibited only a slight rise in [Ca2+]i after AMPA addition.
      These results suggest that the expression of calbindin-D28k is related to the
      expression of Ca2+-permeable AMPA receptors.

PMID- 10971624
TI  - Scorpion alpha and alpha-like toxins differentially interact with sodium channels
      in mammalian CNS and periphery.
AB  - Scorpion alpha-toxins from Leiurus quinquestriatus hebraeus, LqhII and LqhIII,
      are similarly toxic to mice when administered by a subcutaneous route, but in
      mouse brain LqhII is 25-fold more toxic. Examination of the two toxins effects in
      central nervous system (CNS), peripheral preparations and expressed sodium
      channels revealed the basis for their differential toxicity. In rat brain
      synaptosomes, LqhII binds with high affinity, whereas LqhIII competes only at
      high concentration for LqhII-binding sites in a voltage-dependent manner. LqhII
      strongly inhibits sodium current inactivation of brain rBII subtype expressed in
      HEK293 cells, whereas LqhIII is weakly active at 2 microM, suggesting that LqhIII
      affects sodium channel subtypes other than rBII in the brain. In the periphery,
      both toxins inhibit tetrodotoxin-sensitive sodium current inactivation in dorsal
      root ganglion neurons, and are strongly active directly on the muscle and on
      expressed muI channels. Only LqhII, however, induced repetitive end-plate
      potentials in mouse phrenic nerve-hemidiaphragm muscle preparation by direct
      effect on the motor nerve. Thus, rBII and sodium channel subtypes expressed in
      peripheral nervous system (PNS) serve as the main targets for LqhII but are
      mostly not sensitive to LqhIII. Toxicity of both toxins in periphery may be
      attributed to the direct effect on muscle. Our data elucidate, for the first
      time, how different toxins affect mammalian central and peripheral excitable
      cells, and reveal unexpected subtype specificity of toxins that interact with
      receptor site 3.

PMID- 10971625
TI  - Synchronization of circadian firing rhythms in cultured rat suprachiasmatic
      neurons.
AB  - The circadian clock in mammals is located in the suprachiasmatic nucleus (SCN)
      which consists of multiple oscillating neurons. Integration of the cellular
      oscillations is essential for the generation of a single circadian period in the
      SCN. By using a multielectrode dish (MED), we measured circadian firing rhythms
      in individual SCN neurons for more than 2 weeks continuously, and examined the
      involvement of synaptic communication in the synchronization of circadian
      rhythms. Cross-correlation analysis of spontaneous action potentials revealed
      that a neuron pair was functionally connected by synapses when their circadian
      rhythms were synchronized. No correlation was found between the paired neurons
      whose circadian rhythms were not synchronized. Calcium (Ca2+)-dependent synaptic
      transmission in the cellular communication was indicated by dose-dependent
      lengthening of an intercellular spike interval and loss of spike correlation with
      a Ca2+ channel blocker. Approximately 60% of the SCN neurons in culture were
      immunoreactive to antibodies against gamma-aminobutyric acid (GABA) or glutamic
      acid decarboxylase (GAD). Spontaneous firing of all the neurons tested was either
      increased or decreased by bicuculline, the GABAA receptor antagonist. These
      findings indicate that synaptic communication plays a critical role in the
      synchronization of circadian rhythms in individual SCN neurons and the GABAergic
      transmission is involved in the synchronization mechanism.

PMID- 10971626
TI  - The HIV-1 coat protein gp120 and some of its fragments potently activate native
      cerebral NMDA receptors mediating neuropeptide release.
AB  - The objective of this study was to investigate the effects of the HIV-1 envelope
      protein gp120 and its peptide fragments on the function of N-methyl-D-aspartate
      (NMDA) receptors mediating release of cholecystokinin (CCK) and somatostatin
      (SRIF). These are nonconventional NMDA receptors recently found to be activated
      by glycine or D-serine 'only'. The release of cholecystokinin-like
      immunoreactivity (CCK-LI) and of somatostatin-like immunoreactivity (SRIF-LI)
      elicited by 12 mM K+ from superfused rat neocortex synaptosomes was potently
      increased by gp120, its cyclic V3 loop and the linear V3 sequence BRU-C-34-A, but
      not by RP-135 (a central portion of BRU-C-34-A). The EC50 values of gp120 were
      0.02 nM (CCK-LI release) and 0.01 nM (SRIF-LI release). The releasing effect of
      gp120 was prevented by blocking the glycine site or the ion channel of NMDA
      receptors, but not the glutamate recognition site; in addition, the gp120 effect
      was strongly inhibited by nanomolar concentrations of Zn2+ ions and by low
      micromolar concentrations of ifenprodil. It is concluded that gp120 acts as a
      very potent agonist at the glycine site of NMDA receptors sited on CCK- and SRIF
      releasing nerve endings; the protein is able to activate the receptor channel in
      the absence of glutamate. Gp120 activates the receptors through its V3 loop as
      peptide fragments related to V3 retain near-maximal activity. The sensitivity of
      the gp120 effect to both Zn2+ and ifenprodil would not be incompatible with the
      idea that these NMDA receptors contain the triple subunit combination
      NR1/NR2A/NR2B.

PMID- 10971627
TI  - Cellular uptake and spread of the cell-permeable peptide penetratin in adult rat
      brain.
AB  - Investigation of normal and pathological diseases of the central nervous system
      (CNS) has been hampered by the inability to effectively manipulate protein
      function in vivo. In order to address this important topic, we have evaluated the
      ability of penetratin, a novel cell-permeable peptide consisting of a 16-amino
      acid sequence derived from a Drosophila homeodomain protein, to act as a carrier
      system to introduce a cargo into brain cells. Fluorescently tagged penetratin was
      injected directly into rat brain, either into the striatum or the lateral
      ventricles, and rats were perfusion-fixed 24 h later in order to assess the brain
      response to the peptide. Immunohistochemistry following intrastriatal injection
      showed that injection of 10 microg penetratin caused neurotoxic cell death and
      triggered recruitment of inflammatory cells in a dose-dependent fashion. Doses of
      1 microg or less resulted in reduced toxicity and recruitment of inflammatory
      cells, but interestingly, there was some spread of the penetratin. Injections of
      an inactive peptide sequence, derived from the same homeodomain, caused little
      toxicity but could still, however, trigger an inflammatory response.
      Intraventricular injections showed extensive inflammatory cell recruitment but
      minimal spread of either peptide. These results suggest that a dose of 1 microg
      of penetratin peptide is suitable for directing agents to small, discrete areas
      of the brain and as such is an interesting new system for analysing CNS function.

PMID- 10971628
TI  - The circadian cycle of mPER clock gene products in the suprachiasmatic nucleus of
      the siberian hamster encodes both daily and seasonal time.
AB  - The circadian clock in the hypothalamic suprachiasmatic nuclei (SCN) regulates
      the pattern of melatonin secretion from the pineal gland such that the duration
      of release reflects the length of the night. This seasonally specific endocrine
      cue mediates annual timing in photoperiodic mammals. The aim of this study was to
      investigate how changes in photoperiod influence the cyclic expression of
      recently identified clock gene products (mPER and mTIM) in the SCN of a highly
      seasonal mammal, the Siberian hamster (Phodopus sungorus). Immunocytochemical
      studies indicate that the abundance of both mPER1 and mPER2 (but not mTIM) in the
      SCN exhibits very pronounced, synchronous daily cycles, peaking approximately 12
      h after lights-on. These rhythms are circadian in nature as they continue
      approximately under free-running conditions. Their circadian waveform is
      modulated by photoperiod such that the phase of peak mPER expression is prolonged
      under long photoperiods. mPER1 protein is also expressed in the pars tuberalis of
      Siberian hamsters. In hamsters adapted to long days, the expression of mPER1 is
      elevated at the start of the light phase. In contrast, there is no clear
      elevation in mPER1 levels in the pars tuberalis of hamsters held on short
      photoperiods. These results indicate that core elements of the circadian
      clockwork are sensitive to seasonal time, and that encoding and decoding of
      seasonal information may be mediated by the actions of these transcriptional
      modulators.

PMID- 10971629
TI  - Photoperiod differentially regulates the expression of Per1 and ICER in the pars
      tuberalis and the suprachiasmatic nucleus of the Siberian hamster.
AB  - Previous studies demonstrated that the clock gene Per1 and the transcription
      factor ICER are expressed rhythmically in the suprachiasmatic nucleus (SCN) and
      in the pars tuberalis (PT). In the Syrian hamster the duration of photoperiod
      affects the amplitude of gene expression in the PT, and melatonin administered
      before lights-on suppressed the peak of Per1/ICER expression; these effects were
      not seen in the SCN. It was speculated that the inefficacy of melatonin was due
      to the low density of melatonin receptors in the SCN of this species. The aim of
      the present study was to determine whether this phenomenon also occurs in the
      Siberian hamster, which expresses a higher density of melatonin receptors in the
      SCN. Male Siberian hamsters were housed in long days (16 h light : 8 h dark) or
      short days (8 h light : 16 h dark) and expression of Per1 and ICER mRNA was
      studied by in situ hybridization. The expression of Per1 and ICER mRNA in the PT
      peaked 3 h following lights-on (ZT3) under both photoperiods. The amplitudes of
      these peaks were greatly attenuated under short photoperiod. In the SCN, the
      duration of Per1 gene expression was proportional to the length of the light
      phase, but only a modest amplitude effect was observed. Injections of melatonin
      (25 microg) 1 h before lights-on significantly reduced the expression of both
      genes in the PT at ZT3, but had no effect in the SCN. These data demonstrate that
      photoperiod-dependent amplitude modulation of Per1 and ICER gene expression in
      the PT is conserved across species, and reinforce the argument that this
      phenomenon is driven by melatonin.

PMID- 10971630
TI  - Differential modulation of AMPA receptors by cyclothiazide in two types of
      striatal neurons.
AB  - The modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)
      receptor-mediated currents by cyclothiazide was investigated in acutely isolated
      cells from rat striatum with whole-cell patch-clamp recording. Single-cell
      reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify
      medium spiny and giant aspiny neurons and to determine their AMPA receptor
      subunit composition mostly in separate experiments. After pretreatment with
      cyclothiazide, kainate-induced AMPA responses were more strongly potentiated in
      medium spiny than in giant aspiny neurons; cyclothiazide induced a ninefold
      leftward shift in the kainate concentration-response curve for medium spiny
      neurons (not giant aspiny neurons). The EC50s for the cyclothiazide potentiation
      did not differ substantially between medium spiny neurons and giant aspiny
      neurons. The recovery of kainate-activated currents from modulation by
      cyclothiazide was slower for medium spiny neurons than for giant aspiny neurons.
      Medium spiny neurons expressed GluR-A, GluR-B and GluR-C, but not GluR-D subunits
      in both flip and flop splice variants. All giant aspiny neurons expressed GluR-A
      and GluR-D, exclusively in the flop form, half of them also expressed GluR-B and
      GluR-C. This is in keeping with slow and fast desensitization kinetics in medium
      spiny neurons and giant aspiny neurons, respectively, and differences in
      cyclothiazide modulation. The rate of cyclothiazide dissociation from the AMPA
      receptor, activated by glutamate, was approximately 90 times slower in medium
      spiny neurons than in giant aspiny neurons. In giant aspiny neurons (not medium
      spiny neurons) this rate was strongly dependent on the presence of an agonist; 1
      mM glutamate increased it 30-fold. Thus, two major cell groups in the striatum
      display distinct AMPA receptor compositions carrying specific properties of
      glutamate responses. Excitatory transmission will thus be differentially affected
      by cyclothiazide-type compounds.

PMID- 10971631
TI  - A modulatory role for protein phosphatase 2B (calcineurin) in the regulation of
      Ca2+ entry.
AB  - The Ca2+/calmodulin-dependent protein phosphatase 2B (PP2B) also known as
      calcineurin (CN) has been implicated in the Ca2+-dependent inactivation of Ca2+
      channels in several cell types. To study the role of calcineurin in the
      regulation of Ca2+-channel activity, phosphatase expression was altered in NG108
      15 cells by transfection of sense and antisense plasmid constructs carrying the
      catalytic subunit of human PP2Bbeta3. Relative to mock-transfected (wild-type)
      controls, cells overexpressing calcineurin showed dramatically reduced high
      voltage-activated Ca2+ currents which were recoverable by the inclusion of 1
      microM FK506 in the patch pipette. Conversely, in cells with reduced calcineurin
      expression, high-voltage-activated Ca2+ currents were larger relative to
      controls. Additionally in these cells, low-voltage-activated currents were
      significantly reduced. Analysis of high-voltage-activated Ca2+ currents revealed
      that the kinetics of inactivation were significantly accelerated in cells
      overexpressing calcineurin. Following the delivery of a train of depolarizing
      pulses in experiments designed to produce large-scale Ca2+ influx across the cell
      membrane, Ca2+-dependent inactivation of high-voltage-activated Ca2+ currents was
      increased in sense cells, and this increase could be reduced by intracellular
      application of 1 mM BAPTA or 1 microM FK506. These data support a role of
      calcineurin in the negative feedback regulation of Ca2+ entry through voltage
      operated Ca2+ channels.

PMID- 10971632
TI  - Adaptive changes in the nigrostriatal pathway in response to increased 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration in the mouse.
AB  - Although several adaptive mechanisms have been identified that mask the existence
      of Parkinson's disease and delay the onset and aggravation of motor symptoms, the
      timescale and implications of this compensatory process remain an enigma. In
      order to examine: (i) the nature of the dopaminergic adaptive mechanisms that
      come into action; (ii) their sequential activation in relation to the severity of
      degeneration; and (iii) their efficacy with regard to the maintenance of a normal
      level of basal ganglia activity, we analysed the brains of mice treated daily
      with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP, 4 mg/kg, i.p.) and
      killed at 5-day intervals from day 0 (D0) to D20. Our results demonstrate the
      sequential activation of two compensatory mechanisms: (i) an increase in striatal
      tyrosine hydroxylase (TH) protein content attested by the persistence of TH
      immunolabelling up to D15, contrasting with the decrease observed in both the
      number of nigral TH-immunoreactive neurons (-70.2%) and striatal dopamine content
      (-38.4%); (ii) a downregulation of DA uptake in surviving terminals at D20 (73.4%
      of nigral degeneration). At this point, the failure of adaptive mechanisms to
      maintain striatal dopaminergic homeostasis is also illustrated by an increase in
      the cytochrome oxidase activity of substantia nigra pars reticulata, a marker of
      neuronal function. It has been postulated that an increase in dopamine release
      per pulse could constitute an adaptive mechanism. The data we present from our
      MPTP mice model infirm this hypothesis. This study explores the link between the
      degree of nigral degeneration and the sequential activation of dopaminergic
      compensatory mechanisms in the nigrostriatal pathway and, in so doing, proposes a
      rethink of the paradigm applied to these mechanisms.

PMID- 10971633
TI  - Galanin-R1 and -R2 receptor mRNA expression during the development of rat brain
      suggests differential subtype involvement in synaptic transmission and
      plasticity.
AB  - The present study employed 35S-labelled oligonucleotides and in situ
      hybridization to examine the distribution in the developing rat brain of mRNA
      encoding two galanin receptor subtypes, i.e. Gal-R1 and Gal-R2. Gal-R1 and/or Gal
      R2 mRNA was detected at embryonic day (E) 20 and from postnatal day (P) 0-70. Gal
      R1 mRNA was highly expressed in olfactory regions, ventral hippocampal CA fields,
      dorsomedial thalamic areas and many hypothalamic nuclei at all ages studied. In
      adult brain, Gal-R2 mRNA was most abundant in the dentate gyrus, anterior and
      posterior hypothalamus, raphe and spinal trigeminal nuclei, and in the dorsal
      motor nucleus of the vagus. At P0-P7, Gal-R2 mRNA was more widely distributed and
      abundant than at other ages, with highest levels of expression detected
      throughout the neocortex and thalamus. Thus, Gal-R2 transcripts had a more
      restricted distribution than Gal-R1 and were differentially abundant at different
      ages, while the distribution and relative abundance of Gal-R1 mRNA did not alter
      substantially during postnatal development. In general, Gal-R1 and -R2 mRNAs were
      localized in regions previously shown to contain [125I]-galanin binding sites and
      galanin-positive terminals in adult brain. Galanin-immunostaining was assessed in
      postnatal brain to determine whether peptide innervation correlated with observed
      transient receptor expression, but was not particularly enriched in Gal-R2 mRNA
      positive areas of P4 or P7 brain. These results, together with earlier findings
      [e.g. Burazin, T. C. D. & Gundlach, A. L. (1998) J. Neurochem., 71, 879-882],
      suggest that Gal-R1 receptors have a broad role in normal synaptic transmission,
      while Gal-R2 receptors, in addition to a similar role in particular pathways, may
      be involved in processes prominent during the establishment and maturation of
      synaptic connections in developing brain and during neural damage and repair in
      the mature nervous system.

PMID- 10971634
TI  - Gluco- and mineralocorticoid receptor-mediated regulation of neurotrophic factor
      gene expression in the dorsal hippocampus and the neocortex of the rat.
AB  - Gluco- and mineralocorticoid receptors (GR and MR) act via common promoter
      elements but may exert different effects on gene regulation in various regions of
      the forebrain. In order to separately analyse the role of GR and MR in the
      regulation of neurotrophic factor genes and their receptors, we used
      adrenalectomy and subsequent hormone injections in the rat as a model system.
      Twenty-four hours after adrenalectomy rats were injected with a single dose of
      corticosterone (2 and 10 mg/kg), aldosterone (0.5 mg/kg) or the synthetic
      glucocorticoid agonist RU 28362 (4 mg/kg). Gene expression of basic fibroblast
      growth factor (bFGF) and its high-affinity receptors [fibroblast growth factor
      receptor subtypes 1-3 (FGF-R1, FGF-R2, FGF-R3)], as well as brain-derived growth
      factor (BDNF) and neurotrophin-3 (NT-3) was analysed at 4 h after the hormone
      injection in CA1-CA4 (cornus of Ammon areas of the hippocampus) and dentate gyrus
      of the dorsal hippocampus and in neocortex by means of in situ hybridization. We
      found that bFGF is regulated in CA2, CA3 and dentate gyrus by GR and MR together,
      and in CA1, CA4 and neocortex by GR alone. FGF-R2 expression in the hippocampus
      seems to be regulated only by MR, while BDNF expression appears to depend on both
      receptors. FGF-R1, FGF-R3 and NT-3 were only moderately affected by the hormone
      activation of GR and MR acting in concert or alone in the various regions. Thus,
      the present findings suggest that the adrenal cortical system through GR and MR
      participate in the control of neurotrophic factor signalling in a highly
      subregion- and cellular-dependent manner.

PMID- 10971635
TI  - Implication of Bcl-2 and Caspase-3 in age-related Purkinje cell death in murine
      organotypic culture: an in vitro model to study apoptosis.
AB  - Neuronal cell death is an essential feature of nervous system development and
      neurodegenerative diseases. Most Purkinje cells in murine cerebellar organotypic
      culture die when taken from 1-5-day-old mice (P1-P5), whereas they survive when
      taken before or after these ages. Using DNA gel electrophoresis, terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and
      electron microscopic analyses, we were able to show that this massive Purkinje
      cell death is apoptotic in nature and reaches a peak at P3. From the several
      endogenous genes known to be involved in the apoptotic process, we have focused
      on two: the bcl-2 and the caspase-3 that encode for anti-apoptotic and pro
      apoptotic proteins, respectively. Immunostaining for activated Caspase-3
      correlated with Purkinje cell death. A better survival of Purkinje cells was
      observed in P3 slices taken from hu-bcl-2 transgenic mice, and in slices treated
      with z-DEVD.fmk (an inhibitor of numerous caspases). Thus, these two genes are
      implicated in the age-related Purkinje cell apoptosis in organotypic culture. As
      Purkinje cell death in vitro takes place at the same age as Purkinje cells
      engaged in intense synaptogenesis and dendritic remodeling in vivo, we propose
      that this apoptosis reflects a naturally occurring Purkinje cell death during
      this critical period.

PMID- 10971636
TI  - alpha1-adrenergic receptor-induced slow rhythmicity in nonrespiratory cervical
      motoneurons of neonatal rat spinal cord.
AB  - Previous studies have reported that the alpha1-adrenergic system can activate
      spinal rhythm generators belonging to the central respiratory network. In order
      to analyse alpha1-adrenergic effects on both cranial and spinal motoneuronal
      activity, phenylephrine (1-800 microM) was applied to in vitro preparations of
      neonatal rat brainstem-spinal cord. High concentration of phenylephrine
      superfusion exerted multiple effects on spinal cervical outputs (C2-C6),
      consisting of a lengthening of respiratory period and an increase in inspiratory
      burst duration. Furthermore, in 55% of cases a slow motor rhythm recorded from
      the same spinal outputs was superimposed on the inspiratory activity. However,
      this phenylephrine-induced slow motor rhythm generated at the spinal level was
      observed neither in inspiratory cranial nerves (glossopharyngeal, vagal and
      hypoglossal outputs) nor in phrenic nerves. Whole-cell patch-clamp recordings
      were carried out on cervical motoneurons (C4-C5), to determine first which
      motoneurons were involved in this slow rhythm, and secondly the cellular events
      underlying direct phenylephrine effects on motoneurons. In all types of
      motoneurons (inspiratory and nonrespiratory) phenylephrine induced a prolonged
      depolarization with an increase in neuronal excitability. However, only
      nonrespiratory motoneurons showed additional rhythmic membrane depolarizations
      (with spiking) occurring in phase with the slow motor rhythm recorded from the
      ventral root. Furthermore the tonic depolarization produced in all motoneurons
      results from an inward current [which persists in the presence of tetrodotoxin
      (TTX)] associated with a decrease in neuron input conductance, with a reversal
      potential varying as a Nernstian function of extracellular K+ concentration. Our
      results indicate that the alpha1-adrenoceptor activation: (i) affects both the
      central respiratory command (i.e. respiratory period and inspiratory burst
      duration) and spinal inspiratory outputs; (ii) induces slow spinal motor
      rhythmicity, which is unlikely to be related to the respiratory system; and
      (iii), increases motoneuronal excitability, probably through a decrease in
      postsynaptic leak K+ conductance.

PMID- 10971637
TI  - Running and cocaine both upregulate dynorphin mRNA in medial caudate putamen.
AB  - Physical activities such as long-distance running can be habit forming and
      associated with a sense of well-being to a degree that justifies comparison with
      drug-induced addictive behaviours. To understand molecular similarities and
      dissimilarities controlling these behaviours in humans we compared the effects of
      running in running wheels to the effects of chronic cocaine or morphine
      administration on mRNA levels in brain reward pathways in the inbred Fischer and
      Lewis rat strains. These strains are both inbred from the Sprague-Dawley strain;
      Lewis rats display a higher preference towards addictive drugs and running than
      do Fischer rats. After chronic cocaine or running a similar increase of dynorphin
      mRNA in medial caudate putamen was found in the Lewis rat, suggesting common
      neuronal adaptations in this brain region to both cocaine and running. Fischer
      and Lewis rats both responded to cocaine with increased dynorphin mRNA levels in
      medial caudate putamen. However, only Lewis rats increased dynorphin mRNA after
      running, possibly reflecting the much higher degree of running by the Lewis
      strain as compared to the Fischer strain. Moreover, the running-induced
      upregulation of dynorphin mRNA was blocked by the opioid receptor antagonist
      naloxone. We suggest that running increases dynorphin mRNA by a mechanism that
      involves endogenous opioids. The voluntary wheel-running model in rats might be
      used to study natural reward and compulsive behaviours and possibly also to
      screen candidate drugs for treatment of compulsive disorders.

PMID- 10971638
TI  - Early postnatal maturation of GABAA-mediated inhibition in the brainstem
      respiratory rhythm-generating network of the mouse.
AB  - It is well established that GABAA-mediated postsynaptic potentials are excitatory
      in many brain regions during embryonic and early postnatal life. The pre
      Botzinger complex (PBC) in the brainstem is an essential component of the
      respiratory rhythm-generating network, where GABAA-mediated inhibition plays a
      critical role in generating a stable respiratory rhythm in adult animals. In the
      present study, using the perforated patch technique, we investigated the
      maturation of GABAA receptor-mediated effects on rhythmically active PBC neurons
      and on the motor output in slice preparations from P0-15 neonatal mice. The
      reversal potential of GABAA receptor-mediated current (EGABA-A) switched from
      depolarizing to hyperpolarizing within the first postnatal week. EGABA-A was 
      13.7 +/- 9.8 mV at P0, then it changed to -44.8 +/- 7.0 mV at P2 and -71.5 +/-
      6.8 mV at P4. Perfusion of bicarbonate-free saline has no detectable influence on
      EGABA-A, indicating that a lack of Cl- extrusion during P0-3 is mainly
      responsible for early GABAA-ergic excitation. At the network level, blockade of
      GABAA receptors with bicuculline did not significantly change the frequency of
      rhythmic bursts recorded from hypoglossal nerve roots before P3, whereas it
      increased the coefficient of variation. After P3, bicuculline increased burst
      frequency with little effect on the coefficient of variation. Thus, chloride
      mediated inhibition, which appears in PBC neurons after P3, coincides with the
      appearance of GABAA-mediated modulation of the respiratory rhythm. GABAA receptor
      activated inhibition may therefore be necessary for frequency modulation in the
      respiratory network beginning on the fourth postnatal day in the mouse brainstem.

PMID- 10971639
TI  - Release and elimination of dopamine in vivo in mice lacking the dopamine
      transporter: functional consequences.
AB  - In mice lacking the dopamine transporter (DAT), the amplitude of dopamine (DA)
      release and the kinetics of dopamine elimination were measured in vivo using
      carbon fibre electrodes combined with amperometry. DA release was evoked by
      electrical stimulation of the medial forebrain bundle. The amplitude of DA
      release per pulse was lower (7% in striatum and 21% in nucleus accumbens) than in
      wild-type mice. Inhibition of monoamine oxidases (MAOs) by pargyline, but not of
      catechol-O-methyltransferase (COMT) by tolcapone, slowed down DA elimination in
      knockout mice. As DA half-life was two orders of magnitude higher in these mice,
      the DA diffusion distance was 10-times higher than in wild-types (100 and 10
      microm, respectively). In knockout mice, alpha-methyl-p-tyrosine induced a much
      faster decline of DA release and haloperidol was less effective in potentiating
      DA release. Therefore, DA release was more dependent on DA synthesis than in
      normal animals but was less influenced by D2 autoregulation. Dopaminergic neurons
      exhibit two kinds of discharge activity, i.e. single spikes and bursts of 2-6
      action potentials. In wild-type mice, stimuli mimicking bursts evoked significant
      increases in extracellular DA over its basal level sustained by tonic activity.
      However, in mice lacking the DAT, low frequency firing resulted in consistently
      high extracellular DA levels that could not be distinguished from DA levels
      achieved by high frequency firing. Therefore, the burst firing activity cannot be
      specifically translated into phasic changes in extracellular DA. This deficit
      might contribute to the difficulties of these mice in spatial cognitive function.

PMID- 10971640
TI  - Coupling between lumbar and sacral motor networks in the neonatal rat spinal
      cord.
AB  - We have studied the rhythm-generating capabilities of the lumbar, sacral and
      coccygeal (Co) areas using an isolated spinal cord preparation of the newborn
      rat. The bath-application of a mixture of N-methyl-D-L-aspartate (NMA) and
      serotonin (5-HT) on the whole spinal cord induced a coordinated rhythmic activity
      that could be recorded from the lumbar to the coccygeal ventral roots. The phase
      relationships and mean burst duration between the activity in the rostral lumbar
      segments and the activity in the sacral segments was analysed. The direct
      activation of the sacral network, by using sections or by selective
      pharmacological activation, showed that these caudal segments possess their own
      rhythmogenic capability. By combining section experiments and compartmentation of
      the spinal cord, we demonstrated that a strong coupling exists between the lumbar
      and sacral motor networks. In addition, we found that in an intact spinal cord
      the activity of the sacral networks is driven by the lumbar networks. We have
      found that different modes of coordination between the lumbar and the sacral
      activity may occur. Finally, we have shown that the coupling between the lumbar
      and sacral networks can be modified by sensory inputs, suggesting that the spinal
      machinery could modulate and adapt the coupling of these two spinal networks.

PMID- 10971642
TI  - Human area V5 and motion in the ipsilateral visual field.
AB  - We have studied area V5 of the human brain with visually-evoked potential (VEP)
      and functional magnetic resonance imaging (fMRI) methods, using hemifield motion
      stimuli. Our results confirmed the presence of an ipsilateral field
      representation in V5 and found: (i) a delay in the ipsilateral response in V5,
      irrespective of the hemifield stimulated; (ii) a longer ipsilateral delay for
      left hemifield than for right hemifield stimulation; and (iii) in a patient with
      a section of the splenium, an absent ipsilateral response for right but not left
      hemifield stimulation. Together with neurophysiological and anatomical evidence
      in the monkey, our non-invasive spatial and temporal imaging studies in man
      reveal that ipsilateral V5 is activated by motion signals transferred from
      contralateral V5. The asymmetry of ipsilateral delay in normal subjects and the
      asymmetrical loss of ipsilateral response following splenial section imply that
      signals related to visual motion are transferred from one V5 to the other through
      two segregated pathways.

PMID- 10971641
TI  - Postnatal handling alters the activation of stress-related neuronal circuitries.
AB  - Postnatal handling, as a crucial early life experience, plays an essential role
      in the development of hypothalamo-pituitary-adrenal axis responses to stress. The
      impact of postnatal handling on the reactivity of stress-related neuronal
      circuitries was investigated in animals that were handled for the first 21 days
      of life and as adults they were exposed to physical (ether) or emotional
      (restraint) challenge. To assess neuronal activation we relied on the induction
      of immediate-early gene product c-Fos and analysed its spatial and temporal
      distribution at various time intervals after stress. Ether and restraint commonly
      activated parvocellular neurons in the hypothalamic paraventricular nucleus, and
      resulted in activation of brain areas providing stress-related information to the
      hypothalamic effector neurons and/or in regions governing autonomic and
      behavioural responses to stress. Beyond these areas, the strength and timing of c
      Fos induction showed stressor specificity in olfactory and septal region, basal
      ganglia, hypothalamus, hippocampal formation, amygdala and brainstem. Handled
      rats displayed a lower number of c-Fos-positive cell nuclei and weaker staining
      intensity than non-handled controls in the hypothalamic paraventricular nucleus,
      bed nucleus of stria terminalis, central nucleus of amygdala, hippocampus,
      piriform cortex and posterior division of the cingulum. Significant differences
      were revealed in timing of c-Fos induction as a function of stressor and early
      life experience. Together, these data provide functional anatomical evidence that
      environmental enrichment in the early postnatal period attenuates the reactivity
      of stress-related neuronal circuitries in the adult rat brain.

PMID- 10971643
TI  - Differences in the effect of chronic and acute caffeine on self-administration of
      cocaine in mice.
AB  - We have compared the ability of an acute injection of caffeine (3 mg/kg, i.p.)
      and long-term peroral caffeine consumption for 10 days ( approximately 150
      mg/kg/day in tap water) to affect cocaine self-administration in mice. The peak
      plasma and brain levels of caffeine and its metabolites were similar in the two
      experimental set-ups. Moreover, the levels reached are close to those obtained in
      humans upon coffee ingestion. Neither type of caffeine administration affected
      the reinforcing effect of cocaine, defined as a selective increase in nose-poke
      responses in mice self-administering cocaine compared to their yoked controls.
      However, caffeine injection increased the amount of cocaine self-administered
      whereas caffeine drinking reduced it. A low dose of cocaine, by itself
      essentially ineffective, produced an increase in c-fos and NGFI-A mRNA in the
      cerebral cortex in mice that had been drinking caffeine. An acute caffeine
      injection also enhanced the immediate early gene response to cocaine, but to a
      lesser degree. Cocaine and caffeine also synergistically increased NGFI-A
      expression in caudate-putamen. Thus, regular caffeine drinking decreased the
      cocaine intake without significantly affecting its reinforcing properties,
      perhaps because it enhanced the activation of the predominantly inhibitory
      frontal cortical areas produced by low doses of cocaine.

PMID- 10971644
TI  - Systemic administration of the propargylamine CGP 3466B prevents behavioural and
      morphological deficits in rats with 6-hydroxydopamine-induced lesions in the
      substantia nigra.
AB  - The ability of CGP 3466B to attenuate the behavioural and morphological
      consequences of experimentally induced cell death was investigated in a recently
      updated animal model of Parkinson's disease. 6-Hydroxydopamine was infused
      bilaterally into the substantia nigra pars compacta of rats that were pretreated
      with desimipramine. Treatment with CGP 3466B (0.0014-1.4 mg/kg, injected
      subcutaneously) or its solvent was begun 2 h after the 6-OHDA injection, and
      maintained twice daily for 14 days. After a washout period of 14 days, changes in
      motor behaviour were evaluated, using the open field test (analysis of normal and
      abnormal stepping, e.g.) and the paw test (analysis of retraction time of limbs).
      Changes in learning and memory were evaluated with the help of the Morris water
      maze task. Following immunocytochemical staining of tyrosine hydroxylase, the
      extent of the lesion was quantified using a computerized system. CGP 3466B
      prevented all deficits produced by 6-hydroxydopamine (6-OHDA), though at
      different doses. It prevented: abnormal stepping (0.0014-0.014 mg/kg); increased
      forelimb and hindlimb retraction time (0.014-0.14 mg/kg and 0.0014-0.14 mg/kg,
      respectively); delayed learning (1.4 mg/kg); and reduced tyrosine hydroxylase
      immunoreactivity in the substantia nigra (0.0014-0.014 mg/kg). CGP 3466B (0.0014
      0.14 mg/kg) induced no deficits in sham-treated rats. CGP 3466B (1.4 mg/kg),
      however, did not show any benefit on motor deficits in 6-OHDA-lesioned rats, and
      induced abnormal movements and decreased the tyrosine hydroxylase
      immunoreactivity in the substantia nigra pars compacta and the ventral tegmental
      area of sham-lesioned animals. It is concluded that CGP 3466B prevents all 6-OHDA
      induced behavioural and immunocytochemical deficits, though at different doses.
      CGP 3466B is suggested to be a valuable agent for inhibiting the dopaminergic
      degeneration in patients with Parkinson's disease.

PMID- 10971645
TI  - The basolateral amygdala complex is involved with, but is not necessary for,
      rapid acquisition of Pavlovian 'fear conditioning'.
AB  - A major hypothesis about lateral/basolateral amygdala complex (BLC) function in
      memory proposes that the BLC is the site where conditioned stimulus-unconditioned
      stimulus (CS-US) associations are formed and permanently stored during Pavlovian
      'fear conditioning.' Thus, according to this hypothesis, the BLC is necessary for
      the acquisition and expression of both discrete-cue and contextual Pavlovian fear
      conditioning. This hypothesis clearly requires that animals with complete lesions
      of the BLC be completely unable to acquire Pavlovian fear conditioning. In this
      experiment, distribution of training and testing trials over three sessions
      revealed that rats with complete BLC lesions rapidly acquired a contextual CS-US
      association (as assessed with freezing behaviour), although their performance, as
      expected, did not equal that of sham operated controls. Irrespective of the
      nature of the freezing deficit relative to controls, the learning in the BLC
      lesioned rats strongly indicates that Pavlovian fear conditioning CS-US
      associations can be rapidly acquired in the absence of the BLC, and that the BLC
      cannot therefore be necessary for their acquisition.

PMID- 10971646
TI  - Increased acetylcholine release in the rat medial prefrontal cortex during
      performance of a visual attentional task.
AB  - Recent studies have suggested a functional link between cortical cholinergic
      output and attentional task demands, whereby acetylcholine (ACh) release is
      regulated according to the outcome of ongoing behaviour. To explore this
      hypothesis we measured ACh efflux in the rat medial prefrontal cortex (mPFC)
      during between-session manipulations of the cognitive demands of an attentional
      task. Rats were trained to detect visual stimuli in a five-choice serial reaction
      time task (5-CSRTT) which involves sustained and divided attention. Following
      habituation to tethering and implantation with a microdialysis probe in the mPFC,
      rats were tested in the 5-CSRTT for three consecutive days, with different
      lengths of stimulus duration. During performance of the 5-CSRTT we measured
      robust, reproducible, task-related increases in ACh release in the mPFC across
      all sessions. Variations of the stimulus duration from the standard 0.5 s
      resulted in the predicted behavioural effects (reductions and increases in choice
      accuracy with 0.25 s and 5 s, respectively), but there was no evidence of either
      greater changes in ACh release in the more demanding condition or smaller changes
      in the less demanding condition. By contrast, in the session with 5-s stimulus
      duration there was a positive correlation between prefrontal cortical ACh efflux
      and the total number of trials completed. In summary, the present study shows
      that ACh efflux in the rat mPFC is increased during performance of a 5-CSRTT, but
      has found no evidence to support a specific relationship between cholinergic
      cortical output and attentional performance.

PMID- 10971647
TI  - Ipsilateral involvement of primary motor cortex during motor imagery.
AB  - To investigate whether motor imagery involves ipsilateral cortical regions, we
      studied haemodynamic changes in portions of the motor cortex of 14 right-handed
      volunteers during actual motor performance (MP) and kinesthetic motor imagery
      (MI) of simple sequences of unilateral left or right finger movements, using
      functional magnetic resonance imaging (fMRI). Increases in mean normalized fMRI
      signal intensities over values obtained during the control (visual imagery) task
      were found during both MP and MI in the posterior part of the precentral gyrus
      and supplementary motor area, both on the contralateral and ipsilateral
      hemispheres. In the left lateral premotor cortex, fMRI signals were increased
      during imagery of either left or right finger movements. Ipsilateral cortical
      clusters displaying fMRI signal changes during both MP and MI were identified by
      correlation analyses in 10 out of 14 subjects; their extent was larger in the
      left hemisphere. A larger cortical population involved during both contralateral
      MP and MI was found in all subjects. The overall spatial extent of both the
      contralateral and the ipsilateral MP + MI clusters was approximately 90% of the
      whole cortical volume activated during MP. These results suggest that overlapping
      neural networks in motor and premotor cortex of the contralateral and ipsilateral
      hemispheres are involved during imagery and execution of simple motor tasks.

PMID- 10971648
TI  - Volume-regulated anion channels do not contribute extracellular adenosine during
      the hypoxic depression of excitatory synaptic transmission in area CA1 of rat
      hippocampus.
AB  - We investigated whether volume-regulated anion channels (VRACs) contributed to
      the accumulation of extracellular adenosine during hypoxia in area CA1. The rapid
      hypoxic depression of the fEPSP was greatly attenuated by the selective adenosine
      A1 receptor antagonist DPCPX (50 nM), but not affected by the VRAC blockers
      tamoxifen (10-30 microM) or DNDS (1 mM). Our data argue against the efflux of
      adenosine per se or its precursor ATP through VRACs as making a significant
      contribution to extracellular adenosine during the early stages of hypoxia.

PMID- 10971649
TI  - Ultrastructural localization of mint1 at synapses in mouse hippocampus.
AB  - Mint1 and mint2 were isolated in the course of seeking the protein ligands to
      munc18-1, a neuronal protein essential for synaptic vesicle exocytosis. The mint
      family of proteins has been highly conserved in the course of evolution, being
      retained from C. elegans to mammals. Several lines of biochemical and genetic
      evidence have suggested that mint1 and LIN-10, its homologue in C. elegans,
      function at synapses in the brain. Because the precise subcellular location of
      mint1 is incompletely known, we used immunostaining to examine the distribution
      of mint1 in the mouse brain including ultrastructural localization in synapses.
      Strong, finely punctate mint1 immunolabeling was detected throughout the brain,
      including cerebral cortex, striatum, hippocampus, thalamus, basal ganglia and
      cerebellum. At the most synapses in the molecular layer, mint1 was particularly
      abundant at the active zone and to a lesser extent in association with synaptic
      vesicles in the presynaptic terminals. In contrast, a very few synapses showed
      mint1 immunoreactivity in the postsynaptic density and there was no synapse
      double-positive in presynaptic and postsynaptic terminals. Mint1 distribution
      within presynaptic terminals overlapped that of munc18-1. These localization
      results are consistent with previously demonstrated biochemical interactions and
      strongly support functions of mint1 in synaptic vesicle exocytosis and synaptic
      organization in the central nervous system.

PMID- 10971650
TI  - Induction of neuronal death by alpha-synuclein.
AB  - The molecular and cellular mechanisms underlying neuronal loss in
      neurodegenerative diseases are unclear. It is generally thought that aggregation
      of mutated, abnormally modified or abnormally folded proteins leads to the
      accumulation of extracellular, intracellular or intranuclear deposits that
      severely compromise cell physiology, leading to the death of the affected
      neurons. However, there is growing evidence that neuronal apoptosis in the
      absence of obvious pathological deposits could have a serious impact on the
      pathogenesis of neurodegenerative diseases. alpha-Synuclein has been implicated
      in aetiology and pathogenesis of certain neurodegenerative diseases, although the
      precise role of this protein in neurodegeneration is uncertain. The normal
      functions of alpha-synuclein and other members of the synuclein family in the
      development and function of the nervous system also remain elusive. Here we show
      that overexpression of wild-type and mutant forms of alpha-synuclein in cultured
      neurons, but not the closely related persyn (gamma-synuclein), causes apoptosis.
      These findings suggest that abnormalities of alpha-synuclein metabolism could
      lead to the neuronal loss occurring in certain forms of neurodegeneration before
      the formation of characteristic pathological lesions.

PMID- 10971651
TI  - The role of tightly bound ATP in Escherichia coli tRNA nucleotidyltransferase.
AB  - BACKGROUND: The CCA-adding enzyme [ATP(CTP): tRNA nucleotidyltransferase (EC.
      2.7.7.25)] catalyses the addition of the conserved CCA sequence to the 3'
      terminus of tRNAs. All CCA-adding enzymes are classified into the
      nucleotidyltransferase superfamily. In the absence of ATP, the Escherichia coli
      CCA-adding enzyme displays anomalous poly(C) polymerase activity. RESULTS: We
      show that CCA-adding enzyme over-expressed in E. coli exists in an ATP-bound
      form. The affinities of ATP and CTP towards the enzyme were estimated by several
      methods, and the dissociation constants for ATP and CTP were determined to be 6.3
      and 188 microM, respectively. AMP-incorporation terminated the
      nucleotidyltransferase reaction, while in the absence of ATP, the enzyme
      continued poly(C) polymerization. In the case of a tRNA substrate with a mutation
      in the T-loop region, normal CC was added at a much slower rate compared with the
      wild-type, but anomalous poly(C) polymerization occurred at the same rate as in
      the wild-type. CONCLUSION: Based on the findings outlined above, we concluded
      that the E. coli CCA-adding enzyme possesses at least two distinct nucleotide
      binding sites, one responsible for ATP binding and the other(s) for CTP binding.
      The addition of ATP from the tight ATP binding site terminates nucleotide
      incorporation, thus limiting poly(C) polymerization to CCA. It is also suggested
      that during anomalous poly(C) polymerization, tRNA translocates from the tRNA
      binding site upon the third C addition.

PMID- 10971652
TI  - MIDA1 is a sequence specific DNA binding protein with novel DNA binding
      properties.
AB  - BACKGROUND: Id proteins not only regulate cell differentiation negatively, but
      they also promote growth and apoptosis. To know the mechanism of how Id regulates
      cell fate, we previously isolated an Id-associating protein, MIDA1, which
      positively regulates cell growth. Its predicted amino acid sequence contains
      tryptophan-mediated repeats (Tryp-med repeats) similar to the DNA binding region
      of the c-Myb oncoprotein. We determined whether MIDA1 can bind to DNA in a
      sequence specific manner by PCR-assisted binding site selection. RESULTS: We
      identified a 7-base sequence (GTCAAGC) surrounded by a 1-3 bp palindromic
      sequence as the DNA sequence recognized by the Tryp-med repeats of MIDA1. This
      motif is located within the 5'-flanking sequence of several growth regulating
      genes. Gel shift assays revealed that this sequence and a certain length of
      flanking DNA are necessary for MIDA1 to bind DNA in a stable manner. Methylation
      interference and DNase I footprint analysis suggested that the DNA binding of
      MIDA1 is resistant to DNA methylation and that MIDA1 does not specifically
      localize on this particular motif. CONCLUSIONS: We concluded that MIDA1 is a
      novel sequence-specific DNA binding protein with some different properties from
      the usual transcription factors and that MIDA1 may act as a mediator of Id
      mediated growth-promoting function through its DNA binding activity.

PMID- 10971653
TI  - The conserved nuclear receptor Ftz-F1 is required for embryogenesis, moulting and
      reproduction in Caenorhabditis elegans.
AB  - BACKGROUND: Nuclear receptors are essential players in the development of all
      metazoans. The nematode Caenorhabditis elegans possesses more than 200 putative
      nuclear receptor genes, several times more than the number known in any other
      organism. Very few of these transcription factors are conserved with components
      of the steroid response pathways in vertebrates and arthropods. Ftz-F1, one of
      the evolutionarily oldest nuclear receptor types, is required for steroidogenesis
      and sexual differentiation in mice and for segmentation and metamorphosis in
      Drosophila. RESULTS: We employed two complementary approaches, direct mutagenesis
      and RNA interference, to explore the role of nhr-25, a C. elegans ortholog of Ftz
      F1. Deletion mutants show that nhr-25 is essential for embryogenesis. RNA
      interference reveals additional requirements throughout the postembryonic life,
      namely in moulting and differentiation of the gonad and vulva. All these defects
      are consistent with the nhr-25 expression pattern, determined by in situ
      hybridization and GFP reporter activity. CONCLUSIONS: Our data link the C.
      elegans Ftz-F1 ortholog with a number of developmental processes. Significantly,
      its role in the periodical replacement of cuticle (moulting) appears to be
      evolutionarily shared with insects and thus supports the monophyletic origin of
      moulting.

PMID- 10971654
TI  - Molecular analysis of zebrafish photolyase/cryptochrome family: two types of
      cryptochromes present in zebrafish.
AB  - BACKGROUND: Cryptochromes (CRY), members of the DNA photolyase/cryptochrome
      protein family, regulate the circadian clock in animals and plants. Two types of
      animal CRYs are known, mammalian CRY and Drosophila CRY. Both CRYs participate in
      the regulation of circadian rhythm, but they have different light dependencies
      for their reactions and have different effects on the negative feedback loop
      which generates a circadian oscillation of gene expression. Mammalian CRYs act as
      a potent inhibitor of transcriptional activator whose reactions do not depend on
      light, but Drosophila CRY functions as a light-dependent suppressor of
      transcriptional inhibitor. RESULTS: We cloned seven zebrafish genes that carry
      members of the DNA photolyase/cryptochrome protein family; one (6-4)photolyase
      and six cry genes. A sequence analysis and determination of their in vitro
      functions showed that these zebrafish cry genes constitute two groups. One has a
      high sequence similarity to mammalian cry genes and inhibits CLOCK:BMAL1 mediated
      transcription. The other, which has a higher sequence similarity to the
      Drosophila cry gene rather than the mammalian cry genes, does not carry
      transcription inhibitor activity. The expressions of these cry genes oscillate in
      a circadian manner, but their patterns differ. CONCLUSIONS: These findings
      suggest that functionally diverse cry genes are present in zebrafish and each
      gene has different role in the molecular clock.

PMID- 10971655
TI  - Transactivation mechanisms of mouse clock transcription factors, mClock and
      mArnt3.
AB  - BACKGROUND: The Arnt3 (also termed as BMAL1 or MOP3)/Clock heterodimer is a
      positive regulator of circadian rhythm and activates the transcription of target
      genes such as per1 and vasopressin. RESULTS: We investigated the transcriptional
      mechanism of mArnt3/mClock heterodimer. While mClock did not possess any distinct
      activation domain, mArnt3 contained a transcriptional activation domain at the
      most C-terminal end, the activity of which was not expressed, even in the one
      hybrid system, until it was bound by mClock. It has been suggested that mClock
      plays a regulatory or structural role in exerting a transcription enhancing
      effect of the mArnt3/mClock heterodimer. Deletion proceeding from amino acids 559
      492 of mClock markedly reduced the transactivation activity of mArnt3/mClock
      heterodimer, in consistence with the results of the Clock-delta 19 mutant. Yeast
      and mammalian two-hybrid systems revealed that CBP and p300 interacted with
      mArnt3 via the CREB binding domain. The In vivo interaction between mArnt3 and
      CBP was confirmed by the GST pull down assay. CONCLUSION: Taken together, these
      results suggest that the mArnt3/mClock heterodimer exerted its transactivation
      activity via CBP or p300 interacting with mArnt3 in the heterodimer with mClock
      playing a structural or regulatory role in the transactivation process.

PMID- 10971657
TI  - Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases
      is indispensable for mTOR function in vivo and in vitro.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) belongs to the family of
      phosphoinositide (PI)-kinase-related kinases that includes the ataxia
      telangiectasia gene product (ATM). mTOR plays a critical role in controlling
      translational effectors such as p70 S6 kinase alpha (p70 alpha) and eukaryotic
      initiation factor 4E binding protein 1 (4EBP1). RESULTS: We show that the C
      terminal region of mTOR, which is highly conserved among the PI-kinase-related
      kinases, plays a critical role in the mTOR protein kinase activity. Deletion of
      the C-terminal residues did not adversely affect the expression of mTOR, but
      caused a nearly complete loss of the mTOR protein kinase activity toward both
      4EBP1 and p70 alpha in vitro. These deletions also abolished the ability of a
      rapamycin-resistant mTOR mutant to rescue the activity of p70 alpha from
      inhibition induced by rapamycin in vivo. Furthermore, replacement of Trp2545, a
      conserved residue in the C-terminal region throughout the PI-kinase-related
      kinase family, abolished the function of the mTOR kinase, both in vivo and in
      vitro. However, substitution of 32 C-terminal residues of mTOR with those of ATM
      did not restore the mTOR function. CONCLUSIONS: These findings define an
      indispensable role for the noncatalytic C-terminal region of mTOR and indicate
      that, although this highly conserved region may be important throughout the PI
      kinase-related kinase family, it is not functionally interchangeable within the
      family.

PMID- 10971656
TI  - Adaptor protein Shc undergoes translocation and mediates up-regulation of the
      tyrosine kinase c-Src in EGF-stimulated A431 cells.
AB  - BACKGROUND: Shc is the adaptor protein that exists in three isoforms, P46, P52
      and P66, and acts as a bridge between activated cell surface receptors and
      downstream signalling molecules which act in extracellular signal-regulated cell
      events such as cell cycle progression. In our previous studies, Shc was shown to
      be a substrate of the tyrosine kinase c-Src in vitro and in vivo. RESULTS: Using
      green fluorescent protein-fusion Shc (GFP-Shc), we have shown that following
      epidermal growth factor (EGF) stimulation of A431 cells, all Shc isoforms were
      rapidly recruited from the cytoplasm to the plasma membrane (within 5 min) and
      then redistributed to the cytoplasmic vesicle structures (in the next 10-20 min).
      Indirect immunofluorescent study demonstrated that all Shc isoforms co-localize
      with EGF receptor (EGFR) and activated c-Src in both plasma membranes and
      cytoplasmic vesicle structures. Our previous study has shown that EGF induces the
      indirect association of EGFR and c-Src and activation of c-Src in A431 cells. An
      immunoprecipitation study demonstrated that the EGFR-Src association and c-Src
      activation are augmented in cells expressing GFP-Shc P52 or P66, but not P46. In
      addition, P52 and P66, but not P46, are in association with EGFR-Src complex. We
      also found that EGFR and Shc can be dissociated from c-Src by the addition of a
      synthetic peptide that corresponds to the autophosphorylation site of c-Src.
      Interestingly, the peptide-induced dissociation of the complex was not affected
      by the tyrosine phosphorylation state of the peptide. CONCLUSION: These results
      demonstrated a dynamic subcellular movement of Shc in response to EGF, and
      suggested a hitherto unknown scheme whereby Shc can work not only as a substrate
      of c-Src but also as a mediator of the EGF-induced activation of c-Src in an
      isoform-specific manner.

PMID- 10971658
TI  - The utility of neuroimaging in the evaluation of children with migraine or
      chronic daily headache who have normal neurological examinations.
AB  - OBJECTIVES: To assess the utility of neuroimaging in the evaluation of children
      presenting with two of the most common forms of headache, migraine and chronic
      daily headache, and to determine the utility and pathological yield of
      neuroimaging in specific headache syndromes in children whose neurological
      examinations are normal. METHODS: We retrospectively reviewed the medical records
      of patients coded for headache (ICD 784) in the Pediatric Neurology Clinic at
      Children's Hospital of the King's Daughters between 1997 and 1999. The age range
      considered was between 6 and 18 years. The study focused on the two most common
      types of headache, uncomplicated migraine and chronic daily headache. Only
      patients with normal physical and neurological examinations were considered in
      this analysis. RESULTS: Three hundred two patients were coded for headache within
      the defined age group. One hundred seven (35.4%) patients fulfilled IHS-R
      criteria as having uncomplicated migraine with a normal examination, and 30
      (9.9%) patients fulfilled criteria for chronic daily headache. Twenty-nine (9.6%)
      patients presented with migrainelike symptoms, and 6 (2.0%) presented with
      chronic daily symptoms, but had neurological abnormalities present on
      examination. The remainder of the patients with headache had the following
      etiologies: 50 (16.6%) with secondary headache, 22 (7.3%) with complicated
      migraine, 20 (6.6%) with posttraumatic headache, 13 (4.3%) with seizure-related
      headache, 11 (3.6%) with brain tumors, 10 (3.3%) with tension-type headache, and
      4 (1.3%) with pseudotumor cerebri. Of the 107 patients with migraine, 42 (39.3%)
      received CT scans; 2 (4.8%) of which were considered "abnormal." One of the
      abnormalities was an arachnoid cyst and the other was a dilated Virchow-Robin
      space. Twelve (11.2%) patients with migraine received an MRI, 2 (16.7%) of which
      were considered abnormal. Both of the abnormal findings were Chiari type I
      malformations. Of the 30 patients with chronic daily headache, 17 (56.7%)
      received CT scans, 3 (17.6%) of which were considered abnormal. The abnormalities
      consisted of a maxillary opacification, a mucous retention cyst, and an occult
      vascular malformation. Eight (26.7%) of the patients with chronic daily headache
      had an MRI, 2 (25.0%) of which were abnormal. One of the abnormalities was a
      Chiari I malformation, and the other was an occult vascular malformation.
      CONCLUSION: The yield of neuroimaging in children with uncomplicated migraine and
      normal neurological examination was 3.7%. The yield in children with chronic
      daily headache and normal neurological examination was higher at 16.6%. The
      abnormalities discovered included arachnoid cysts, Chiari I malformations, sinus
      disease, occult vascular malformations and "dilated Virchow-Robin spaces." While
      none of the neuroimaging findings were apparent clinically, their discovery did
      not influence the diagnosis, management, or outcome of the patients. None of the
      abnormalities necessitated surgical intervention or were associated with the
      headache presentation. Therefore, neuroimaging is not warranted in children and
      adolescents with defined clinical headache syndrome diagnoses whose neurological
      examinations are normal.

PMID- 10971659
TI  - Modified-release formulation of tizanidine in chronic tension-type headache.
AB  - The efficacy of the modified-release formulation of tizanidine (Sirdalud) was
      compared with placebo in a randomized, double-blind, parallel-group study of 138
      women and 47 men, aged 18 to 79 years, with a history of chronic tension-type
      headache (IHS categories 2.2 and 2.3). The treatment period was 6 weeks preceded
      by a 2-week prerandomization period. The patients were randomly assigned to
      receive 6-mg Sirdalud, 12-mg Sirdalud MR, or placebo. The study medication was
      taken once per day, orally in the evening. Efficacy was measured by visual analog
      scale, the number of headache-free days, the daily duration of headache, and the
      use of paracetamol. The primary end point was the severity of daily headache
      derived from visual analog scale scores covering the last 2 treatment weeks. One
      hundred sixty patients (56 in the 6-mg group, 49 in the 12-mg group, and 55 in
      the placebo group) completed the study. The severity of the headache decreased
      similarly in the treatment groups and the placebo group. The visual analog scale
      values decreased from the prerandomization values by 53% in the 6-mg group, 48%
      in the 12-mg group, and 52% in the placebo group. The modified-release
      formulation of tizanidine in doses up to 12 mg taken in the evening is not
      superior to placebo in the treatment of chronic tension-type headache. The
      placebo effect was unexpectedly strong in the present study, supporting the view
      that psychophysiological mechanisms are of considerable importance in sustaining
      chronic tension-type headache.

PMID- 10971660
TI  - Reversible cognitive decline accompanies migraine and cluster headaches.
AB  - Vascular headaches, including migraine, cluster, and migrainous transformation to
      chronic daily headaches, are disabling. During and shortly after headache
      intervals, difficulties are reported in concentration, comprehension, and
      communication, not accounted for by nausea, photophobia, or sonophobia. These
      interfere with interpersonal relations and performance at work with economic
      loss. The hypothesis tested and reported here is that cognitive impairments
      comprise an important part of vascular headache diatheses. One hundred ninety-six
      otherwise normative subjects suffering from migraine or cluster, but not tension
      type, headaches (136 women, 63 men; mean age, 46 years) participated in an
      outpatient prospective trial. One hundred thirty-three patients had migraine
      without aura, 39 migraine with aura, 11 periodic cluster (by IHS criteria), and
      13 had migrainous transformation into chronic daily headaches. Neuropsychological
      testing was compared with and without headaches, by combined Mini-Mental Status
      Examination (MMSE), Cognitive Capacity Screening Examination (CCSE), and Hamilton
      Depression Rating Scale (HDRS). During headache intervals, significant decline
      was measured in both CCSE and MMSE scores (P <. 001) without HDRS change in all
      types of vascular headache and independent of headache severity, which often
      improved, or associated physical symptoms. Cognitive decline was promptly
      relieved by serotonin agonists and sleep. Disorders of cerebral serotoninergic
      projection systems appear to cause these reversible cognitive impairments.

PMID- 10971661
TI  - Perceived self-efficacy and headache-related disability.
AB  - BACKGROUND: Headache-specific self-efficacy refers to patients' confidence that
      they can take actions that prevent headache episodes or manage headache-related
      pain and disability. According to social cognitive theory, perceptions of self
      efficacy influence an individual's adaptation to persistent headaches by
      influencing cognitive, affective, and physiological responses to headache
      episodes as well as the initiation and persistence of efforts to prevent headache
      episodes. OBJECTIVE: The objective of the present study was to construct and
      validate a brief measure of headache specific self-efficacy and to examine the
      relationship between self-efficacy and headache-related disability. METHODS: A
      sample of 329 patients seeking treatment for benign headache disorders completed
      the Headache Management Self-Efficacy Scale and measures of headache-specific
      locus of control, coping, psychological distress, and headache-related
      disability. A subset of 262 patients also completed 4 weeks of daily headache
      recordings. RESULTS: As predicted, patients who were confident they could prevent
      and manage their headaches also believed that the factors influencing their
      headaches were potentially within their control. In addition, self-efficacy
      scores were positively associated with the use of positive psychological coping
      strategies to both prevent and manage headache episodes and negatively associated
      with anxiety. Multiple regression analyses revealed that headache severity, locus
      of-control beliefs, and self-efficacy beliefs each explained independent variance
      in headache-related disability.

PMID- 10971662
TI  - A pilot study to measure cognitive efficiency during migraine.
AB  - BACKGROUND AND OBJECTIVES: The measurement of cognitive efficiency during
      migraine has produced conflicting results primarily due to the types of tests
      used. The objectives of this pilot study were two-fold: to measure cognitive
      efficiency during migraine, compared to a migraine-free period, and to evaluate
      the effects of therapy with a 5-HT1 agonist (sumatriptan injection, 6 mg) on the
      cognitive efficiency of migraineurs during a migraine. METHOD: The Headache Care
      Center-Automated Neuropsychological Assessment Metrics was administered to 10
      migraineurs, three times without a migraine, once during a migraine, and three
      times after administration of sumatriptan injection (6 mg). RESULTS: The results
      demonstrated a significant drop in cognitive efficiency during migraine and
      recovery 15 minutes after therapeutic injection. CONCLUSIONS: This pilot study is
      the first to document a significant drop in cognitive functioning during migraine
      and recovery after administration of a migraine-specific medication.

PMID- 10971663
TI  - Assessing the impact of migraine on health-related quality of life: An additional
      use of the quality of well-being scale-self-administered.
AB  - OBJECTIVES: To compare the interviewer-administered Quality of Well-being Scale
      (QWB) with a self-administered form (QWB-SA) for patients with migraine, and to
      compare the health status of migraineurs to other medical populations.
      BACKGROUND: With the increasing need to document the cost-effectiveness of
      treatment for migraine, limitations with both the Medical Outcomes Study Short
      Form-36 items and the QWB have been an impediment to research using cost
      effectiveness as an outcome. Demonstrating the sensitivity of an alternative
      instrument which addresses these limitations would facilitate cost-effectiveness
      analyses on treatments for migraine. METHODS: Eighty-nine adults (87% women)
      known to suffer from migraine were asked to complete both the interviewer
      administered QWB and the self-administered version (QWB-SA) on three occasions.
      The first occasion was on a day when no migraine was experienced in the previous
      7 days. The second and third assessments were completed within 48 hours of the
      onset of a migraine. RESULTS: While both the QWB and the QWB-SA successfully
      distinguished migraine from nonmigraine days, more migraines were reported on the
      QWB-SA. Overall, both instruments showed similar patterns of patient dysfunction
      during a migraine attack. Each component of the QWB-SA successfully distinguished
      migraine from nonmigraine days, and the QWB-SA showed a linear sensitivity to
      pain intensity and disability during a migraine episode. Both instruments are
      able to detect a migraine's effect on multiple domains of quality of life. Study
      participants scored significantly lower on the QWB-SA during a migraine episode
      than several comparison medical populations. CONCLUSIONS: The QWB and the QWB-SA
      appear to have sensitivity to migraine severity, and the ability to quantitate an
      effect in multiple quality-of-life domains. Both measures can be used to
      calculate quality-adjusted life-years, thus facilitating cost-effectiveness and
      health policy work in this important clinical area.

PMID- 10971664
TI  - The efficacy of divalproex sodium in the prophylactic treatment of children with
      migraine.
AB  - OBJECTIVE: To determine the beneficial use of divalproex sodium as a prophylactic
      treatment for migraine in children. BACKGROUND: Previous studies for treatment of
      migraine in adults have shown a greater than 50% reduction in migraine attack
      frequencies. Few data exist, however, regarding the efficacy and safety of
      divalproex sodium use in children with migraine. METHODS: We studied the
      incidence of headache relief in our patients with migraine aged 16 years and
      younger treated with divalproex sodium prophylactically at our institution from
      July 1996 to December 1998 to determine medication dosage used, concomitant
      headache medications, and possible adverse effects. RESULTS: A total of 42
      patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated
      with divalproex sodium for headache. All had a history of migraine with or
      without aura. Baseline headache frequency during a minimum 6-month period was one
      to four headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to
      45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their
      abortive medications. After 4 months' treatment, 50% headache reduction was seen
      in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients
      became headache-free. CONCLUSION: These results indicate divalproex sodium to be
      an effective and well-tolerated treatment for the prophylaxis of migraine in
      children.

PMID- 10971665
TI  - Case reports: postpartum cerebral angiopathy in a patient with chronic migraine
      with aura.
AB  - A 25-year-old woman with a history of chronic severe migraine with aura presented
      in an apoplectic state 1 week after the delivery of her third child. She
      developed a severe headache and within hours lapsed into a coma. A CT scan of the
      brain showed cerebral edema and an occipital hemorrhage. A four-vessel angiogram
      showed diffuse arterial narrowing of all the intracranial vessels with segmental
      narrowing of the suprasellar portion of the internal carotid arteries
      bilaterally. She had no risk factors for stroke or vasculitis. Her pregnancy and
      delivery were uneventful with no preeclampsia or eclampsia. Apart from
      ergometrine at the time of the delivery, no vasoconstrictor drugs were used. She
      recovered spontaneously. Serial CT scans of the brain demonstrated resolution of
      the edema and hemorrhage with the development of cortical and watershed infarcts.
      A repeat cerebral angiogram was normal. She was, therefore, diagnosed as having
      suffered from postpartum cerebral angiopathy, a form of reversible cerebral
      vasoconstriction, called the Call or Call-Fleming syndrome. The relationship
      between migraine and postpartum angiopathy in the development of reversible
      cerebral vasoconstriction is discussed.

PMID- 10971666
TI  - Case reports: chronic paroxysmal hemicrania-tic syndrome.
AB  - The coexistence of chronic paroxysmal hemicrania and trigeminal neuralgia is
      called chronic paroxysmal hemicrania-tic syndrome. We describe the case of a man
      who has suffered both types of pain occurring synchronously but with different
      localization on the ipsilateral side. The pain attacks could be abolished with
      indomethacin and carbamazepine. To the best of our knowledge, this is the third
      case to be reported, the first in the male sex. We review this new disorder and
      discuss the pathophysiology.

PMID- 10971667
TI  - Case reports: sudden worsening of cluster headache: A signal of aneurysmal
      thrombosis and enlargement.
AB  - We report a 55-year-old man presenting with symptoms of cluster headache,
      including throbbing pain behind the left eye, tearing, and rhinorrhea. Magnetic
      resonance imaging and magnetic resonance angiography revealed no abnormalities.
      Two days of intravenous dihydroergotamine resolved his pain. His headaches were
      somewhat relieved with a treatment regimen of 100 mg of imipramine each night, 40
      mg of propranolol twice a day, 250 mg of divalproex three times a day, and
      dihydroergotamine nasal spray for breakthrough headaches. Two months later, the
      severity of his pain increased dramatically. Repeat imaging revealed a large
      thrombosed left posterior communicating artery aneurysm. Following obliterative
      surgery, his headaches are infrequent and mild and resemble tension headaches.
      Dramatic changes in headache characteristics can be an indicator of aneurysmal
      enlargement and thrombosis. This case illustrates the importance of repeat
      imaging when a patient's headache significantly worsens.

PMID- 10971668
TI  - Case reports: headache caused by a spinal cord stimulator in the upper cervical
      spine.
AB  - We report persistent headaches developing in a patient subsequent to the
      placement of a spinal cord stimulator in the upper cervical spine. These
      persistent headaches responded to dihydroergotamine and sumatriptan. Headaches
      ceased upon repositioning of the stimulator lower in the cervical spine. We
      postulate an effect of the device on the trigeminovascular system via the nucleus
      caudalis trigeminalis and/or spinal trigeminal tract.

PMID- 10971669
TI  - Expert opinion: transient headache with numbness of half of the tongue.

PMID- 10971670
TI  - Is it migraine or cluster?

PMID- 10971671
TI  - A persistent migraine aura.

PMID- 10971672
TI  - Sensory stimuli and headache sensitivity.

PMID- 10971673
TI  - Lumbar puncture headache in a patient with Addison disease.

PMID- 10971674
TI  - Clinical pearls for treating patients with headache.

PMID- 10971675
TI  - Identification of enterohepatic Helicobacter species by restriction fragment
      length polymorphism analysis of the 16S rRNA gene.
AB  - BACKGROUND: Restriction fragment-length polymorphism (RFLP) analysis of a 1,200
      bp polymerase chain reaction-amplified DNA fragment of gene coding for 16S rRNA
      was used to generate restriction profiles of 11 enterohepatic Helicobacter spp.
      isolated from various animals and humans. METHODS: The amplicon from each
      Helicobacter sp. was digested with four restriction endonucleases: Alu I, Hinf I,
      Hha I, and Dde I. Alu I digestion produced five patterns that were useful for
      initial differentiation. RESULTS: Most Helicobacter spp. isolated from rodents
      had the same RFLP profiles by Alu I digestion (except H. rodentium and H.
      cholecystus), but they had different RFLP profiles by Hha I digestion. Only H.
      bilis and "H. rappini" mouse isolates could not be readily distinguished by the
      polymerase chain reaction-RFLP method. However, these two species can be
      distinguished using H. bilis specific primers. Some of the Helicobacter spp. have
      an intervening sequence in their 16S rRNA gene, which changes the RFLP patterns;
      in these cases, sequencing is the preferred method to make an appropriate
      diagnosis. CONCLUSIONS: The RFLP method used in this study was straightforward
      and rapid and should prove useful as an adjunct for identification and
      classification of multiple enterohepatic Helicobacter spp.

PMID- 10971676
TI  - Mucosal production of antigastric autoantibodies in Helicobacter pylori
      gastritis.
AB  - BACKGROUND: Apart form bacterial virulence factors of Helicobacter pylori,
      certain host factors influence the pathogenesis of H. pylori gastritis. In
      particular, antigastric autoantibodies that are detectable in the sera of a
      substantial proportion of H. pylori were shown to correlate with the development
      of gastric atrophy. The aim of this study was to analyze the possible antigastric
      autoimmune response in H. pylori gastritis at the site where the action is, i.e.
      , in the gastric mucosa. MATERIAL AND METHODS: Gastric biopsy specimens from
      antrum and corpus mucosa of 24 H. pylori-infected and of 33 noninfected patients
      were cultured for 3 days, and tissue culture supernatants were analyzed for the
      amount of locally produced IgA and IgG. Antigastric autoantibodies were screened
      in the sera and in the supernatants by means of immunohistochemistry. RESULTS:
      The infected patients had significantly higher concentrations of locally produced
      IgA, whereas the IgG concentrations were virtually the same in infected and
      noninfected patients. IgG or IgA antigastric autoantibodies, or both, were
      detectable only in the sera (38%) and supernatants (17%) of infected patients.
      Interestingly, the patient with the strongest local autoimmune response showed
      body-predominant H. pylori gastritis, with destruction of gastric glands and
      atrophy of the body mucosa. CONCLUSIONS: These results demonstrate that
      antigastric autoimmune reactions are detectable at the site of the disease and
      might be relevant for the pathogenesis of gastric mucosa atrophy in H. pylori
      gastritis.

PMID- 10971677
TI  - Circulating T-cell response to Helicobacter pylori infection in chronic
      gastritis.
AB  - BACKGROUND: Helicobacter pylori elicits a specific humoral and cellular immune
      response. There is increasing evidence that the type of T-cell response
      contributes to clinical outcome in H. pylori infection. MATERIALS AND METHODS:
      The host response to H. pylori infection in 34 subjects with chronic gastritis
      was examined in terms of T-cell proliferation and cytokine production in whole
      blood cultures stimulated or unstimulated with H. pylori acid-glycine extract
      antigens (AGE). RESULTS: The proliferative response in whole-blood cultures was
      similar for both H. pylori-positive and -negative subjects stimulated with H.
      pylori AGE. While an increase in interferon-gamma (IFN-gamma) production was
      observed from both H. pylori-positive and -negative subjects with gastritis,
      significantly higher levels of IFN-gamma were detected in the former when
      stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable
      regardless of antigen stimulation. However, if an in situ IL-4 antibody capture
      assay was used, antigen-independent production of IL-4 was detected, but there
      was no difference between H. pylori-positive and -negative subjects with
      gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was
      increased, with no decrease in the levels of secretion of IFN-gamma. IL-4
      production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti
      CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture
      inhibited the production of IL-4. CONCLUSION: The results suggest that a shift
      toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4
      production from CD4+ T cells follows eradication. We suggest that the
      downregulation of mucosal inflammation consequent on reduction in antigen levels
      or removal of downregulation after eradication of H. pylori contributes to this
      shift in cytokine balance.

PMID- 10971678
TI  - Differentiation of clinical Helicobacter pullorum isolates from related
      Helicobacter and Campylobacter species.
AB  - BACKGROUND: Helicobacter pullorum, first detected in the liver and intestinal
      contents of poultry, was defined as a new species in 1994. This organism has
      since been isolated from humans with gastroenteritis. Phenotypic as well as
      genotypic methods have been used to identify H. pullorum associated with cases of
      human disease. MATERIALS AND METHODS: Clinical isolates were submitted for
      identification to the National Laboratory for Enteric Pathogens by Provincial
      Public Health Laboratories within Canada. Phenotypic characterization was
      conducted using a variety of growth and biochemical tests including oxidase,
      catalase, indoxyl acetate, H2S production in triple sugar iron (TSI) agar,
      antimicrobial susceptibility testing, and fatty acid analysis. Genotypic
      identification was performed using a polymerase chain reaction-restriction
      fragment-length polymorphism (PCR-RFLP) analysis of a 1-kb fragment of the
      Helicobacter 16S rRNA gene. RESULTS: During the last 7 years (1993-1999) a total
      of 11 isolates of H. pullorum were detected from patients with gastroenteritis
      for inclusion in this study. Typically, these isolates were oxidase and catalase
      positive, produced optimal growth at 42 degrees C, and produced H2S in TSI. Of
      these 11 isolates, 1 showed DNase activity, while another did not produce H2S in
      TSI, and only 2 showed tolerance to 1% bile. Antimicrobial susceptibility assays
      indicated that 6 of the 11 strains were resistant to nalidixic acid. The fatty
      acid profiles of the isolates were similar to each other and provided a
      distinguishing profile from the other related species. Genetically identical and
      distinct species-specific restriction fragment-length polymorphism (RFLP)
      patterns were produced using the restriction enzymes Bsr I and Dde I. CONCLUSION:
      Phenotypic and genotypic procedures were used to identify H. pullorum.
      Interspecies phenotypic variability was apparent and supported the use of a
      polyphasic approach for identification. Similarities to the more prominent human
      pathogens Campylobacter coli and C. lari were also noted. The use of a
      combination of phenotypic and, in particular, genotypic markers for H. pullorum
      should prove valuable both for epidemiological investigations and for the
      diagnosis of disease related to this emerging human pathogen.

PMID- 10971679
TI  - Helicobacter pylori entry into human gastric epithelial cells: A potential
      determinant of virulence, persistence, and treatment failures.
AB  - BACKGROUND AND OBJECTIVES: Intracellular location of Helicobacter pylori in human
      gastric epithelial cells has been observed in biopsies. Whether this reflects an
      ability to invade host cells and establish an intracellular niche remains to be
      determined. METHODS: The interactions between a clinical isolate of H. pylori and
      primary cell cultures from human gastric epithelium or the human epithelial cell
      line HEp-2 were monitored using time-lapse photography. This technique allows
      studies of the dynamics of host-microbial interactions. RESULTS: H. pylori cells
      readily approached and established close contacts with epithelial cells followed
      by uptake of the bacteria into the cellular cytoplasm. Entry into epithelial
      cells was achieved through an active process of bacterial motility and
      penetration of the cell membranes. In conventional invasion assays using HEp-2
      cells, an increased internalization in a strain producing the vacuolating
      cytotoxin was observed, compared to the isogenic VacA knockout mutant.
      CONCLUSION: Invasion of gastric epithelium represents a hitherto unappreciated
      trait of H. pylori that could contribute to the bacterium's ability to establish
      persistent infection that evades the mucosal immune defense and sometimes also
      antimicrobial therapy. A small number of bacterial cells with a transient
      intracellular habitat could serve as a seeder population, providing a backup for
      a constantly challenged and fluctuating luminal population.

PMID- 10971680
TI  - Helicobacter pylori infection in asymptomatic children: comparison of diagnostic
      tests.
AB  - BACKGROUND: Childhood is known to be a major risk period for acquiring
      Helicobacter pylori infection. Studies of the epidemiology of H. pylori infection
      depend on the validity of the diagnostic tools used to detect the infection in
      the pediatric setting. This study aims to conduct a combination of diagnostic
      tests on the same children, evaluate the sensitivity and the specificity of IgG
      antibody testing compared with the 13C-urea breath test, and examine the
      variability in the prevalence of H. pylori infection in asymptomatic children
      based on the use of different diagnostic tests. METHODS: 13C-urea breath test
      (13C-UBT), whole blood FlexSure (systemic antibodies), and OraSure (salivary
      antibodies) tests were conducted on 287 asymptomatic children (151 boys, 136
      girls; ages 2-18 years). The three tests were conducted on each child during the
      same day. The prevalence was calculated using each test independently. RESULTS:
      H. pylori infection was detected in 32%, 22%, or 18% of the studied children,
      based on UBT, OraSure, or FlexSure, respectively. A total of 103 children tested
      positive for any one test (92 on UBT, 8 on FlexSure, 3 on OraSure), giving a
      prevalence of 35% based on the "parallel" method. Only 39 children tested
      positive in all three tests, giving a prevalence of 14% based on the "serial"
      method. Using the UBT as the gold standard, the sensitivity of FlexSure and
      OraSure were 48% and 65%, respectively, and the specificity of both tests was
      greater than 95%. When we applied the parallel method, the sensitivity and
      specificity of the combined antibody tests (FlexSure + OraSure) compared to the
      UBT were 71% and 95%, respectively. CONCLUSIONS: Among asymptomatic children,
      there is a wide variation in the prevalence of H. pylori infection based on the
      diagnostic test used. The study shows that antibody assays are less suitable than
      the UBT. However, under certain conditions, the IgG assays (combined systemic,
      salivary, or both) are less expensive alternative tools to the UBT for
      epidemiological studies in children.

PMID- 10971681
TI  - A new rapid test for detecting anti-Helicobacter pylori antibody excreted into
      urine.
AB  - BACKGROUND: Helicobacter pylori infection has been one of the most common
      infectious diseases in the world, whereas a gold standard for identifying its
      infection has not yet been established. The specific test will depend on the
      particular clinical, epidemiological, and scientific requirements. We recently
      developed a new type of rapid test to detect H. pylori antibody excreted into
      urine; the test requires only 20 minutes. The purpose of this study was to
      examine the accuracy of this rapid test. METHODS: The performance of the rapid
      test was compared with those of a histological search through Giemsa staining and
      of an assay for detecting antibodies in serum by a commercially available ELISA
      kit. The patients, totaling 117 (male, 62, female, 55; average age, 51.6 years),
      included those with peptic ulcer endoscopically diagnosed and excluded cases that
      were subjected to eradication therapy in the past. RESULTS: With respect to the
      determinations of H. pylori identified by the microscopical test and the serum
      antibody assay, our kit had a sensitivity of 92. 0% and a specificity of 93.1%,
      and the agreement of determination of H. pylori infection was as high as 91.5%
      and 92.3%, respectively. CONCLUSIONS: The rapid test for antibodies to H. pylori
      in urine could detect H. pylori infection easily, rapidly, and noninvasively and
      would be useful in general practice for screening patients with dyspeptic
      symptoms.

PMID- 10971682
TI  - Characterization of a culture method to recover Helicobacter pylori from the
      feces of infected patients.
AB  - BACKGROUND: Helicobacter pylori is difficult to culture from stool. Multiple
      efforts from multiple laboratories have been unsuccessful, and the optimal
      conditions to recover H. pylori from stool are still not known. Recovery of H.
      pylori from feces of infected individuals is important for the performance of
      molecular epidemiological investigations, especially in children, where their
      symptoms do not warrant endoscopy to recover the organism. METHODS: Fresh fecal
      specimens (noncathartic) were obtained from 19 known H. pylori-infected patients
      and were processed to recover the organism. Fresh fecal specimens (noncathartic)
      were also obtained from three known H. pylori-negative individuals (controls) to
      determine whether H. pylori could be isolated from stools seeded with known
      concentrations of the organism. Treatment of the fecal suspensions with
      cholestyramine, a basic anion exchange resin that binds bile acids, was used in
      an attempt to enhance recovery of H. pylori by sequestering bile acids that are
      inhibitory to H. pylori growth. H. pylori was identified based on colony
      morphology, cell morphology, Gram's stain, biochemical reactions, and polymerase
      chain reaction for two H. pylori genes. RESULTS: Among 19 patients, H. pylori was
      cultured at least once from 3 and three times from 2 (5 of 19). Feces that were
      seeded with H. pylori and obtained from three H. pylori-negative volunteer
      controls yielded positive recovery in all instances. CONCLUSION: We have
      confirmed that it is possible to culture H. pylori from human stool, but the
      procedure for optimal recovery has still not been defined.

PMID- 10971683
TI  - Double-blind comparison of absorbable colloidal bismuth subcitrate and
      nonabsorbable bismuth subnitrate in the eradication of Helicobacter pylori and
      the relief of nonulcer dyspepsia.
AB  - BACKGROUND: Bismuth is widely used for the eradication of H. pylori, especially
      in developing countries, although there are concerns over its neurotoxicity.
      Whether bismuth has to be absorbed in humans to act against H. pylori is not
      known. In this study, we compared "absorbable" (colloidal bismuth subcitrate) and
      "nonabsorbable" (bismuth subnitrate) bismuth as part of triple therapy in the
      eradication of H. pylori. MATERIALS AND METHODS: A double-blind, randomized,
      placebo-controlled trial was carried out with 120 H. pylori-positive patients
      with nonulcer dyspepsia. Group CBS + Ab (n = 35) received colloidal bismuth
      subcitrate (one tablet qds), amoxicillin (500 mg qds), and metronidazole (400 mg
      tds). Group BSN + Ab (n = 35) received bismuth subnitrate (two tablets tds) and
      the same antibiotics. Group Ab (n = 35) received placebo bismuth (two tablets
      tds) and the antibiotics. Group BSN (n = 15) received bismuth subnitrate (two
      tablets tds) and placebo antibiotics. Bismuth was taken for 4 weeks and the
      antibiotics for the first 2 weeks. H. pylori eradication, side effects,
      compliance, pre- and post-treatment symptom scores, and bismuth absorption were
      assessed. RESULTS: H. pylori eradication was 69%, 83%, 31%, and 0% in CBS + Ab,
      BSN + Ab, Ab, and BSN, respectively. Side effects, compliance, and symptom relief
      were similar in all groups, but blood bismuth levels were significantly greater
      in CBS + Ab than the other three groups. CONCLUSION: The efficacy of bismuth
      based therapies as part of triple therapy in the eradication of H. pylori is
      unrelated to absorption. Hence, the use of effective but poorly absorbed bismuth
      preparations should be encouraged for bismuth-based eradication therapies.

PMID- 10971684
TI  - Solubility, absorption, and anti-Helicobacter pylori activity of bismuth
      subnitrate and colloidal bismuth subcitrate: In vitro data Do not predict In vivo
      efficacy.
AB  - OBJECTIVES: The aim of this study was to compare the dissolution,
      bioavailability, and anti-Helicobacter pylori activity of bismuth subnitrate and
      colloidal bismuth subcitrate. This could, first, provide insights into the
      mechanism of action of bismuth and, second, help to develop optimal therapeutic
      strategies. METHODS: Solubility and aquated size of bismuth species were
      determined in human gastric juice, while absorption into blood and urinary
      excretion of bismuth was determined in volunteers. Activity against H. pylori was
      determined in vitro in the presence and absence of antibiotics, while H. pylori
      eradication was compared in vivo. RESULTS: Bismuth from colloidal bismuth
      subcitrate was at least 10% soluble and ultrafilterable and was absorbed in
      volunteers (>0.5%), whereas that from bismuth subnitrate was insoluble and not
      absorbed (<0.01%). Colloidal bismuth subcitrate was active against H. pylori
      (mean inhibitory concentration, </=12.5 microg/ml), while bismuth subnitrate was
      inactive (>400 microg/ml); neither was synergistic with antibiotics. With in vivo
      triple therapy, bismuth subnitrate was as effective as colloidal bismuth
      subcitrate in eradicating H. pylori (74% and 70% eradicated, respectively).
      CONCLUSIONS: Colloidal bismuth subcitrate, unlike bismuth subnitrate, is
      partially soluble, absorbed in humans, and directly toxic to H. pylori in vitro.
      Surprisingly, however, these preparations had similar efficacy in vivo against H.
      pylori within triple therapy, suggesting that bismuth compounds may also exhibit
      indirect antimicrobial effects. We propose that this is an effect on the gastric
      mucus layer. Nonabsorbable bismuth compounds should be preferentially considered
      in bismuth-based therapies against H. pylori, as they would minimize toxicity
      while maintaining efficacy.

PMID- 10971685
TI  - Structural and functional evidence that a B chromosome in the characid fish
      Astyanax scabripinnis is an isochromosome.
AB  - Astyanax scabripinnis possesses a widespread polymorphism for metacentric B
      chromosomes as large as the largest chromosome pair in the A complement. On the
      basis of C-banding pattern, it was hypothesized that these B chromosomes are
      isochromosomes that have arisen by means of centromere misdivision and chromatid
      nondisjunction. In the present paper we test this hypothesis by analysing (i) the
      localization of a repetitive DNA sequence on both B chromosome arms, and (ii)
      synaptonemal complex formation, in order to test the functional homology of both
      arms. Genomic DNA digested with KpnI and analysed by gel electrophoresis showed
      fragments in a ladder-like pattern typical of tandemly repetitive DNA. These
      fragments were cloned and their tandem organization in the genome was confirmed.
      A 51-bp long consensus sequence, which was AT-rich (59%) and contained a variable
      region and two imperfect reverse sequences, was obtained. Fluorescence in situ
      hybridization (FISH) localized this repetitive DNA into noncentromeric
      constitutive heterochromatin which encompasses the terminal region of some
      acrocentric chromosomes, the NOR region, and interstitial polymorphic
      heterochromatin in chromosome 24. Most remarkably, tandem repeats were almost
      symmetrically placed in the two arms of the B chromosome, with the exception of
      two additional small clusters proximally located on the slightly longer arm.
      Synaptonemal complex (SC) analysis showed 26 completely paired SCs in males with
      1B. The ring configuration of the B univalent persisting until metaphase I
      suggests that the two arms formed chiasmata. All these data provided strong
      support for the hypothesis that the B chromosome is an isochromosome.

PMID- 10971686
TI  - Genetic control of self-incompatibility in Senecio squalidus L. (Asteraceae): a
      successful colonizing species.
AB  - Senecio squalidus (Oxford ragwort) is a well-known introduction to the British
      flora that has proved to be an extremely successful colonist over the last 150
      years. Unusually for a colonizing species, S. squalidus is self-incompatible
      (SI). Being a member of the Asteraceae, SI in S. squalidus is expected to be
      sporophytic. This paper presents genetic data showing that the SI system of S.
      squalidus is indeed sporophytic and is controlled by a single multiallelic S
      locus, alleles of which show the dominance/recessive relationships characteristic
      of sporophytic SI (SSI). Early indications are that the number of S alleles in
      populations is low because only four different S alleles were identified in a
      sample of four plants from two distinct populations; one S allele, S1, a
      pollen/stigma recessive allele, was present in all four plants. Forced
      inbreeding, using salt-treatment to overcome SI, was shown to generate 'pseudo
      self-compatible' individuals with weakened SI and a loss/reduction in stigmatic S
      specific discrimination. Relatively high frequencies of unpredictable compatible
      crossing 'anomalies' suggest that a 'gametophytic element' may influence the
      outcome of crosses in certain genetic backgrounds so as to increase levels of
      compatibility when S alleles are shared. Together, these findings indicate a
      genetic 'flexibility' in the SSI system of S. squalidus that could be crucial to
      its success as a colonizer.

PMID- 10971687
TI  - Are flightless Galapaganus weevils older than the Galapagos Islands they inhabit?
AB  - The 15 species in the weevil genus Galapaganus Lanteri 1992 (Entiminae:
      Curculionidae: Coleoptera) are distributed on coastal Peru and Ecuador and
      include 10 flightless species endemic to the Galapagos islands. These beetles
      thus provide a promising system through which to investigate the patterns and
      processes of evolution on Darwin's archipelago. Sequences of the mtDNA locus
      encoding cytochrome oxidase subunit I (COI) were obtained from samples of seven
      species occurring in different ecological zones of the oldest south-eastern
      islands: San Cristobal, Espanola and Floreana, and the central island Santa Cruz.
      The single most parsimonious tree obtained shows two well-supported clades that
      correspond to the species groups previously defined by morphological characters.
      Based on a mtDNA clock calibrated for arthropods, the initial speciation
      separating the oldest species, G. galapagoensis (Linell) on the oldest island,
      San Cristobal, from the remaining species in the Galapagos occurred about 7.2 Ma.
      This estimate exceeds geological ages of the extant emerged islands, although it
      agrees well with molecular dating of endemic Galapagos iguanas, geckos and
      lizards. An apparent explanation for the disagreement between geological and
      molecular time-frames is that about 7 Ma there were emerged islands which
      subsequently disappeared under ocean waters. This hypothesis has gained support
      from the recent findings of 11-Myr-old submarine seamounts (sunken islands),
      south-east of the present location of the archipelago. Some species within the
      darwini group may have differentiated on the extant islands, 1-5 Ma.

PMID- 10971688
TI  - The genetic relationships of two subspecies of striped field mice, Apodemus
      agrarius coreae and Apodemus agrarius chejuensis.
AB  - We obtained 282 base pairs of sequence for the mitochondrial control region of 70
      individuals of Korean striped field mice Apodemus agrarius coreae and Apodemus
      agrarius chejuensis to determine the levels of genetic divergence between these
      morphologically distinct taxa. The DNA sequences showed more genetic diversity
      (pi) in A. agrarius coreae (2.98%) than in A. agrarius chejuensis (1.86%). Our
      data do not support the current concept that the two morphotypes are different
      species, but phylogenetic analysis indicates that animals of A. agrarius coreae
      with large body size from Wan Island cluster with the large-bodied A. agrarius
      chejuensis, and should be included in that taxon. As currently accepted A.
      agrarius coreae is not strictly monophyletic, because the large-bodied samples
      cluster within the range of mitochondrial variation of A. agrarius chejuensis.
      The fact that the two morphotypes do not share mitochondrial haplotypes (chi2=66,
      P < 0.001) suggests that there is little gene flow between them. A molecular
      clock estimate suggests that the two subspecies might have been isolated at the
      time of separation of the islands from the mainland.

PMID- 10971689
TI  - Genetics of adaptive radiation in Hawaiian species of Tetramolopium (Asteraceae).
      III. Evolutionary genetics of sex expression.
AB  - Despite numerous studies of speciation on oceanic islands, few insights exist on
      the genetic changes involved in the origin and diversification of island taxa.
      Here we report a genetic analysis of the evolutionary change in sex expression in
      Hawaiian Tetramolopium. The most diverse clade in the genus is characterized by a
      monoecious breeding system. The breeding system resulted from a change in sex
      expression in disc florets from the ancestral hermaphroditic condition to the
      derived male state. Analysis of an F2 population from a cross between the two
      forms of sex expression indicates two regions of the Tetramolopium linkage map
      are associated with the loss of female function in disc florets. Quantitative
      trait locus mapping of the two linkage groups confirms that two loci control 56%
      of the phenotypic variation of the trait in the F2 population. Additive and
      dominance effects are apparent but no statistical evidence of epistasis was
      found. Several related reproductive traits also have few genetic associations on
      the linkage map, but are generally distinct from the control of sex expression.
      Although modifier loci are likely to be involved, the apparent simple genetic
      change underlying sex expression parallels a major evolutionary diversification
      in Hawaiian Tetramolopium and may have initiated the divergence of this novel
      clade.

PMID- 10971690
TI  - Quantitative genetics of allogamous F2: an origin of randomly fertilized
      populations.
AB  - The quantitative genetic properties are derived for the bulk F2 originating from
      random fertilization (RF) amongst hybrid (F1) individuals. Only its mean appears
      to have been derived previously, and that definition is confirmed (by another
      method). New general equations are found also for all genotype frequencies,
      allele frequencies, inbreeding coefficient, the genotypic, additive-genetic and
      dominance variances, and broad-sense and narrow-sense heritabilities. The
      assumption that such an F2 is a classical RF population is shown to be correct.
      Indeed, the allogamous F2 is a natural origin for the RF population. The
      relationships are given between precedent RF populations (parents) and subsequent
      RF populations following hybridization (allogamous F2). The allogamous F2 is
      generally inbred with respect to its parental F1, the degree depending on the
      hybrid's parents' allele frequencies. At the same time, it is outbred with
      respect to those original parents, and not inbred at all with respect to the
      equivalent RF population. The genotypic variance is generally more than in the
      F1, and likewise for heritabilities. These findings make it possible to evaluate
      the genetic advance from selection and hybridization. The results depend on the
      allele frequencies of the original parents and the degree of overdominance, but
      generally, selection is more advantageous than hybrid vigour.

PMID- 10971691
TI  - The resolution of Californian populations of Liriomyza huidobrensis and Liriomyza
      trifolii (Diptera: Agromyzidae) using PCR.
AB  - Liriomyza trifolii (Burgess) and Liriomyza huidobrensis (Blanchard) are important
      vegetable pests in California. Populations of each species differ in their impact
      in central and southern regions. This difference may be explained by geographical
      or host plant differences in each of the regions. We used random amplified
      polymorphic DNA polymerase chain reactions to assess genetic differences between
      two laboratory populations of each species collected from central and southern
      California. Individual L. trifolii from the two regions could be discriminated by
      the presence/absence of PCR products. No such qualitative differences were
      apparent in PCR products amplified from L. huidobrensis individuals, but the
      origins of individuals could be differentiated using a bootstrap analysis of
      marker frequencies. Marker primers were used to compare field and laboratory
      individuals. No evidence was found for the existence of further populations or of
      hybrid populations in central and southern California. The distribution of
      populations of L. huidobrensis was explained completely by geographical
      differences. As a consequence of the absence of leafminer infestations on the
      same host plant varieties in both regions, factors governing L. trifolii
      population distribution differences were less apparent. The presence of the same
      host plant varieties at both sites suggests that the two L. trifolii populations
      differ in host plant preference.

PMID- 10971692
TI  - Mitochondrial DNA CoI haplotype variation in sibling species of rough
      periwinkles.
AB  - Three sibling species of rough periwinkles are currently recognized: Littorina
      arcana, L. compressa and L. saxatilis. Certain forms of L. saxatilis are also
      argued by some to deserve species status, such as the barnacle-dwelling 'L.
      neglecta' and the lagoonal 'L. tenebrosa'. Relationships between these taxa, and
      between and within representative populations, are investigated using sequence
      analysis and restriction fragment length polymorphism of a mitochondrial DNA
      fragment spanning the cytochrome oxidase I and cytochrome oxidase II gene
      boundary. These data show that there is some sharing of haplotypes between
      species, with L. arcana haplotypes paraphyletic with respect to L. saxatilis
      haplotypes, and L. compressa haplotypes paraphyletic to both L. arcana and L.
      saxatilis haplotypes. Such sharing of mtDNA haplotypes could be a consequence of
      either persistent hybridization or episodes of hybridization, or incomplete
      lineage sorting of ancestral polymorphisms. On the balance of evidence it is
      suggested that the latter, rather than hybridization events, is the more likely
      causal agent of the observed distribution. Intraspecific variation is extensive
      and it is suggested that the patterns of intraspecific polymorphism are
      explainable by a combination of historical factors (the impact of the Pleistocene
      ice-age) and contemporary restrictions to gene flow. It is argued that Littorina
      haplotypes evolved in at least two separate glacial refugia and became scattered
      by the subsequent range expansion around most of the coastline. Recent factors
      such as restricted gene flow and bottlenecks would then be capable of affecting
      the haplotype distribution, resulting in the pattern observed.

PMID- 10971693
TI  - Genetic and environmental components of phenotypic variation in immune response
      and body size of a colonial bird, Delichon urbica (the house martin).
AB  - Directional selection for parasite resistance is often intense in highly social
      host species. Using a partial cross-fostering experiment we studied environmental
      and genetic variation in immune response and morphology in a highly colonial bird
      species, the house martin (Delichon urbica). We manipulated intensity of
      infestation of house martin nests by the haematophagous parasitic house martin
      bug Oeciacus hirundinis either by spraying nests with a weak pesticide or by
      inoculating them with 50 bugs. Parasitism significantly affected tarsus length, T
      cell response, immunoglobulin and leucocyte concentrations. We found evidence of
      strong environmental effects on nestling body mass, body condition, wing length
      and tarsus length, and evidence of significant additive genetic variance for wing
      length and haematocrit. We found significant environmental variance, but no
      significant additive genetic variance in immune response parameters such as T
      cell response to the antigenic phytohemagglutinin, immunoglobulins, and relative
      and absolute numbers of leucocytes. Environmental variances were generally
      greater than additive genetic variances, and the low heritabilities of phenotypic
      traits were mainly a consequence of large environmental variances and small
      additive genetic variances. Hence, highly social bird species such as the house
      martin, which are subject to intense selection by parasites, have a limited scope
      for immediate microevolutionary response to selection because of low
      heritabilities, but also a limited scope for long-term response to selection
      because evolvability as indicated by small additive genetic coefficients of
      variation is weak.

PMID- 10971694
TI  - Historical biogeography and interspecific mtDNA introgression in Euhadra
      peliomphala (the Japanese land snail).
AB  - We assess variation in mitochondrial DNA (mtDNA) using partial sequences (560 bp)
      of the COI gene among populations of Japanese land snails, Euhadra peliomphala.
      Phylogeographical analysis reveals five primary clades that correspond basically
      to five discrete areas: the Boso Peninsula (B), the Kanto area (K), around Lake
      Ashinoko (A), the Northern Izu Peninsula (N), and the Southern Izu Peninsula (S).
      Although there are no current geographical barriers separating these five
      subpopulations, the borders between each area correspond to palaeogeographical
      events during the Pleistocene, such as volcanic activities and the disappearance
      of the landbridge between the Southern Boso area and the mainland of Japan. In
      addition, our analysis of isolation-by-distance and the distribution of pairwise
      sequence differences indicate that haplotypes of the B and K lineages have
      recently increased their population size exponentially. We have also discovered
      interspecific mtDNA introgression between E. peliomphala and the parapatric
      species E. brandtii at the contact zone in the Northern Kanto area. Unexpectedly,
      the E. brandtii-type mtDNA was also found in the populations of E. peliomphala in
      the Southern Boso area. Because recent contact between both species is unlikely,
      the introgressed mtDNA of E. brandtii could be a remnant of past hybridization,
      when E. peliomphala colonized this area via the landbridge that existed in the
      early Pleistocene.

PMID- 10971695
TI  - Bone marrow manifestations of infections and systemic diseases observed in bone
      marrow trephine biopsy review.
AB  - Bone marrow modifications resulting from infections and systemic diseases can be
      studied by analysis of morphology and aetiology. Two types of lesions or
      modifications can be observed, those occurring in the connective tissue
      comprising inflammatory processes, acute and chronic, as well as immune
      reactions, and those involving the normal haematopoietic cell lines, with
      possible hyperplastic or aplastic changes in one or more cell lines. The main
      lesions are described (oedema, haemorrhage, necrosis, suppuration, granulomas,
      lymphoid nodules and hyperplasia, immunoblastic or plasmacytic hyperplasia), as
      well as the main aetiologies. In association, the three main haematopoietic cell
      lines show hyperplasia, hypoplasia, aplasia of one or all of the cell lines,
      sometimes with dysmyelopoiesis. The stroma and vessel reactions comprise
      myelofibrosis, gelatinous transformation or amyloid deposits. The methods for
      identifying aetiological agents are emphasized. It should also be stressed that
      malignant neoplasias of different types involving the bone marrow can be
      responsible for such inflammatory or immune reactions.

PMID- 10971696
TI  - Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a
      report of the CHAMP study group.
AB  - AIMS: Cutaneous benign fibrohistiocytic tumours are among the most common soft
      tissue lesions. Their biological nature, in particular whether they are
      neoplastic or reactive, has long been disputed. Some morphological subtypes can
      be confused with sarcoma. Since available karyotypic data in these lesions are
      scarce, this study was undertaken to determine whether their cytogenetic analysis
      might demonstrate clonality and might help in differential diagnosis. METHODS AND
      RESULTS: Thirteen karyotyped benign cutaneous fibrous histiocytomas (BFH) were
      morphologically reassessed and classified as ordinary BFH (eight cases), cellular
      BFH (four cases), and one ankle-type lesion. Five cases (38%) showed clonal
      cytogenetic changes, although the aberrations varied and did not correlate with
      histological subtypes. Karyotypic aberrations were more common in cellular BFH
      (3/4) than in the ordinary BFH (2/8). CONCLUSIONS: The demonstration of clonal
      chromosome abnormalities, in at least some cases, supports the neoplastic nature
      of cutaneous BFH. The karyotypic changes identified are different from those in
      dermatofibrosarcoma, with which cellular BFH is often confused histologically.

PMID- 10971697
TI  - Ber EP4 and epithelial membrane antigen aid distinction of basal cell, squamous
      cell and basosquamous carcinomas of the skin.
AB  - AIMS: Seventy-five skin tumours were studied to investigate the value of
      immunohistochemistry in differentiating basal cell, squamous cell and
      basosquamous carcinomas of the skin. METHODS AND RESULTS: Archived paraffin
      embedded tissue samples of basal cell carcinomas (n = 39), squamous cell
      carcinomas (n = 23) and basosquamous carcinomas (n = 13) were stained
      immunohistochemically using a panel of antibodies. All of the basal cell
      carcinomas stained positively for Ber EP4, in contrast to the group of squamous
      cell carcinomas, that showed no staining. Basosquamous carcinomas all showed at
      least some areas of Ber EP4 positivity. None of the basal cell carcinomas, but
      most of the squamous cell carcinomas (22 of 23) expressed epithelial membrane
      antigen (EMA). Only one of the basosquamous carcinomas expressed EMA positivity
      focally. CAM 5.2, carcinoembryonic antigen (CEA) and 34betaE12 antibodies lacked
      specificity in relation to the different tumour types. CONCLUSION: Distinction of
      basal and squamous cell carcinomas of the skin can be readily achieved with
      routine immunohistochemistry using Ber EP4 and EMA. Identification of
      basosquamous carcinoma is also facilitated with this method.

PMID- 10971698
TI  - Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell
      neoplasms.
AB  - AIMS: To undertake a comparative evaluation of three antimesothelial markers
      (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin
      (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of
      spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid
      mesotheliomas were studied. Calretinin expression was focally identified in 12
      (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in
      nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity
      with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty
      mixed spindle cells neoplasms were studied. No calretinin expression was
      identified in any case. Thrombomodulin immunoreactivity was identified in four
      (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise
      specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary
      sarcoma originally termed malignant fibrous histiocytoma. None of the
      antimesothelial markers was expressed in the four spindle cell carcinomas
      studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all
      four spindle cell carcinomas (three pulmonary, one renal), both synovial
      sarcomas, both malignant mixed Mullerian tumours, one of three pulmonary
      leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS:
      Immunohistochemistry has a more limited role in the diagnosis and distinction of
      sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a
      broad spectrum cytokeratin with calretinin combines both high sensitivity (77%
      for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid
      mesothelioma and can be diagnostically useful. The mesothelial markers,
      thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of
      sarcomatoid mesothelioma as each shows insufficient antibody sensitivity,
      although together they complement calretinin.

PMID- 10971699
TI  - Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of
      atypical proliferations of the breast.
AB  - AIMS: This study was performed to determine the diagnostic value of keratin 5/6
      (CK 5/6) immunophenotyping on routinely processed breast tissues. METHODS AND
      RESULTS: Six hundred and ninety-nine breast lesions, including normal tissues as
      well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded
      samples from 158 different patients were investigated immunohistochemically,
      following wet autoclave pre-treatment for antigen retrieval. In normal breast
      tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in
      varying amounts. While myoepithelial immunoreactivity was most pronounced in the
      duct system, luminal epithelial immunoreactivity was strongest in the terminal
      duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells
      predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial
      cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an
      expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating
      ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive
      immunostaining for CK 5/6. CONCLUSIONS: Immunophenotyping of keratin 5/6
      expression can be helpful in the diagnosis of atypical hyperplasias and in-situ
      carcinomas of the breast. It is particularly valuable in the differential
      diagnosis between benign and atypical proliferative lesions.

PMID- 10971700
TI  - Chromosomal numerical aberrations are frequent in oesophageal and gastric
      adenocarcinomas: a study using in-situ hybridization.
AB  - AIMS: (i) To investigate and compare the numerical aberrations of chromosomes 7,
      8, 11, 17 and Y in a series of 60 adenocarcinomas of the oesophagus, gastric
      cardia and gastric antrum; and (ii) to specify the sequence of chromosomal
      aberrations occurring during the neoplastic progression of Barrett's oesophagus.
      METHODS AND RESULTS: Chromosomal in-situ hybridization was performed on
      deparaffinized tissue sections from 20 Barrett's adenocarcinomas, 20
      adenocarcinomas of the cardia and 20 adenocarcinomas of the antrum, with
      centromeric alpha satellite DNA probes specific for chromosomes 7, 8, 11, 17 and
      Y, labelled with digoxigenin. Signals were detected by immunoperoxidase staining.
      The copy number for each chromosome was counted in 200 tumour cells nuclei and
      100 lymphocytes as controls. In parallel, the DNA content of the nuclear
      suspensions was measured by flow cytometry. Numerical abnormalities of the five
      chromosomes (loss of the Y chromosome, monosomy, trisomy, and tetrasomy) were
      frequently observed in the three groups of adenocarcinomas (from 40% to 65% of
      the cases). Sixty per cent to 75% of oesophagus and gastric adenocarcinomas were
      DNA-aneuploid. Chromosomal aberrations progressively increased with advancing
      degrees of dysplasia in Barrett's mucosa, with an increasing frequency of trisomy
      and loss of the Y chromosome from non-dysplastic Barrett's mucosa to invasive
      adenocarcinoma, and with monosomy and tetrasomy present only in invasive cancers.
      CONCLUSION: Our study confirms the high frequency of chromosomal numerical
      aberrations in oesophageal and gastric adenocarcinomas, without differences
      between adenocarcinomas of the gastric cardia and antrum. We have shown that
      these alterations occur early during the neoplastic transformation of Barrett's
      mucosa.

PMID- 10971701
TI  - Gastric adenomas and superficial adenocarcinomas display distinct patterns of
      mucin carbohydrate and core protein expression.
AB  - AIMS: To investigate the histogenetic relationship between gastric epithelial
      neoplasms we studied differences in expression of mucin carbohydrate antigens and
      mucin core protein, in normal and metaplastic gastric mucosa, and in gastric
      adenomas and superficial adenocarcinomas. METHODS AND RESULTS: We generated four
      monoclonal antibodies, including HGM72/75 against human gastric mucin and
      HCM14/21 against human colonic mucin, and investigated immunoreactivities of
      these antibodies and MUC2 protein expression in normal and metaplastic gastric
      mucosa, adenomas (15 samples) and superficial adenocarcinomas (intestinal-type,
      77; diffuse-type, 59 samples). HGM72 reacted with mucous neck cells of the fundic
      glands and with pyloric glandular cells whereas HGM75 stained foveolar cells and
      metaplastic goblet cells. Weak binding of HCM14/21 and strong staining with MUC2
      were found in metaplastic goblet cells. Binding of HGM75, HCM14, MUC2, but not
      HGM72 was high in adenomas. An equivalent staining with HGM72 and HGM75 with low
      expression of MUC2 and HCM14 was shown in intestinal-type carcinomas while the
      diffuse-type demonstrated more strong reactivity with HGM75 than with HGM72, MUC2
      and HCM14. Little binding of HCM21 was observed in any specimens. CONCLUSIONS:
      This study demonstrates that adenomas predominantly have a intestinal phenotype,
      but both types of adenocarcinomas retain some cells with a gastric phenotype
      during the early steps of neoplastic development.

PMID- 10971702
TI  - Intercalated duct hyperplasia: possible relationship to epithelial-myoepithelial
      carcinoma and hybrid tumours of salivary gland.
AB  - AIMS: The aims of this study were to ascertain the incidence of intercalated duct
      hyperplasia in association with cases of epithelial-myoepithelial carcinoma
      (EMC), and to explore a possible relationship between them and hybrid carcinomas
      of salivary glands. METHODS AND RESULTS: Seven cases of EMC with sufficient
      surrounding non-tumour parotid were examined. Three cases contained foci of
      intercalated duct hyperplasia adjacent to the tumour. One of the cases was a
      hybrid tumour composed of EMC and mucoepidermoid carcinoma. The hyperplastic
      intercalated ducts formed multiple foci within the salivary parenchyma and were
      composed of bland, uniform ducts. Cytological atypia was not identified.
      CONCLUSIONS: Intercalated duct hyperplasia may be a precursor lesion to EMC.
      Furthermore, it may also explain why EMC is frequently associated with other
      salivary gland carcinomas, so-called hybrid tumours, as well as sharing
      histological features with adenoid cystic carcinoma. Recognition of the latter is
      of particular importance because adenoid cystic carcinoma carries a poor
      prognosis.

PMID- 10971703
TI  - Renal oncocytoma with prominent intracytoplasmic vacuoles of mitochondrial
      origin.
AB  - AIMS: We observed two oncocytomas with prominent intracytoplasmatic vacuoles. To
      investigate if this previously undescribed finding is a diagnostic feature and
      compatible with the diagnosis of oncocytoma, we characterized these vacuoles by
      electron microscopy and immunohistochemistry. METHODS AND RESULTS: The tumours
      were analysed by transmission electron microscopy. Immunohistochemistry was
      performed with antimitochondrial antibody, anti-Golgi-zone antibody, anti
      lysozyme antibody and anti-human-trans-Golgi-network antibody. By electron
      microscopy, the vacuoles were found to be double-membrane-bounded, and some
      contained fragmented christae. Immunohistochemistry showed a positive reaction of
      the vacuoles with anti-mitochondrial antibody. Staining with anti-Golgi-zone
      antibody, anti-lysozyme antibody and anti-human-trans-Golgi-network antibody was
      negative. CONCLUSION: Both tumours are benign oncocytomas. The phenomena of cells
      with prominent intracytoplasmatic vacuoles is not inconsistent with the diagnosis
      of oncocytoma. The vacuoles are of mitochondrial origin and may develop, by
      balloon degeneration, as a mechanism of mitochondrial involution and elimination.

PMID- 10971704
TI  - Inducible nitric oxide synthase expression is increased in the brain in fatal
      cerebral malaria.
AB  - AIMS: Nitric oxide (NO) has been hypothesized to play a major role in the
      pathogenesis of cerebral malaria caused by P. falciparum infection. NO may act as
      a local neuroactive mediator contributing to the coma of cerebral malaria (CM).
      We hypothesized that increased expression of inducible nitric oxide synthase
      (iNOS) may cause increased release of NO, and examined the expression and
      distribution of iNOS in the brain during CM. MATERIAL AND RESULTS: Brain tissues
      from fatal cases of cerebral malaria in Thai adults were examined using
      immunohistochemical staining to detect iNOS. The distribution and strength of
      staining was compared between 14 patients with CM, three of whom were recovering
      from coma, and controls. iNOS expression was found in endothelial cells,
      neurones, astrocytes and microglial cells in CM cases. There was also strong
      staining in macrophages surrounding ring haemorrhages. iNOS staining was
      decreased in recovering malaria cases compared to acute CM, and was low in
      controls. Quantification showed a significant association between the intensity
      and number of iNOS positive vessels with the severity of malaria related
      histopathological changes, although the total number of cells staining was not
      increased compared to recovering CM cases. CONCLUSIONS: This study indicates that
      an acute induction of iNOS expression occurs in the brain during CM. This occurs
      in a number of different cells types, and is increased in the acute phase of CM
      compared to cases recovering from coma. As NO may activate a number of secondary
      neuropathological mechanisms in the brain, including modulators of synaptic
      function, induction of iNOS expression in cerebral malaria may contribute to
      coma, seizures and death.

PMID- 10971705
TI  - Is cutaneous benign fibrous histiocytoma (dermatofibroma) a reactive inflammatory
      process or a neoplasm?

PMID- 10971706
TI  - Hybrid carcinoma of the salivary gland.

PMID- 10971707
TI  - Spirochaetes can colonize colorectal adenomatous epithelium.

PMID- 10971708
TI  - Microglandular adenocarcinoma of the endometrium.

PMID- 10971709
TI  - Hepatocellular adenoma of the placenta: report of a case associated with maternal
      bicornuate uterus and fetal renal dysplasia.

PMID- 10971711
TI  - From this month's histopathology

PMID- 10971710
TI  - Gastric carcinoma with prominent neutrophil infiltration.

PMID- 10971712
TI  - Identification and analysis of Lydia, a LTR retrotransposon from Lymantria
      dispar.
AB  - Degenerative PCR primers to conserved amino acid motifs were used to identify an
      LTR retrotransposon from Lymantria dispar. The isolated retrotransposon, Lydia,
      is 6655 base pairs (bp) in length and contains perfect 300 bp terminal repeats.
      The identified gag and pol related ORFs have a high degree of similarity to the
      corresponding regions of the retrotransposon Ted from Trichoplusia ni, although
      several reading frameshifts and missense mutations are evident. The high degree
      of similarity between Lydia and Ted LTRs lends support for a family of
      lepidopteran retrotransposons. Southern blot analysis of individuals from two
      geographically distinct gypsy moth populations demonstrates that Lydia is found
      in both populations and the position of this element within the genome of these
      isolated populations is variable.

PMID- 10971713
TI  - Evidence for extensive genetic differentiation among populations of the malaria
      vector Anopheles arabiensis in Eastern Africa.
AB  - We describe the geographical population structure of the malaria vector Anopheles
      arabiensis in Eastern Africa. Allelic variation at eight microsatellite loci was
      scored in samples from nine localities along a 4500 km transect from Sudan to
      Mozambique. Highly significant differences in genotype frequencies were found
      between all populations separated by more than 200 km. Populations within Malawi
      separated by 191 km were indistinguishable, as were those within Sudan separated
      by 134 km. FST and rhoST gave significant estimates of isolation by distance.
      These data, lead us to conclude that there are extensive barriers to gene flow in
      this region. The high estimates of Nm (9.4 from FST and 5.2 from rhoST) indicate
      recent range expansion in this species rather than extensive contemporary gene
      flow.

PMID- 10971714
TI  - Ribosomal DNA internal transcribed spacer (ITS2) sequences differentiate
      Anopheles funestus and An. rivulorum, and uncover a cryptic taxon.
AB  - Differentiation among the closely related Afrotropical species comprising the
      Funestus Group is difficult by traditional taxonomic measures. Anopheles
      rivulorum is the second most abundant and widespread species in the Funestus
      Group, and is occasionally collected indoors along with the dominant member and
      major malaria vector, An. funestus. The prospect of misidentification of An.
      rivulorum as An. funestus prompted the development of a rapid, polymerase chain
      reaction (PCR)-based method for identifying these two species. The ribosomal
      internal transcribed spacer 2 (ITS2) was amplified from thirty-five specimens of
      An. rivulorum collected from the extremes of its range: Eastern Africa (Kenya),
      Southern Africa (South Africa) and Western Africa (Burkina Faso). The ITS2 region
      of An. rivulorum ( approximately 380 bp) is sufficiently different in size from
      the ITS2 of An. funestus ( approximately 700 bp) that these species can be
      distinguished by agarose gel electrophoresis of PCR products without further
      manipulation. Comparison of the An. rivulorum and An. funestus ITS2 nucleotide
      sequences revealed such extensive divergence that meaningful alignment was
      impossible, except for a 25 bp island near the 5' end. Intraspecific sequence
      comparisons revealed no variation among An. rivulorum individuals collected from
      the same country. However, sequence divergence was 2% between specimens from
      South Africa and Kenya, and nearly tenfold higher ( approximately 19%) between
      specimens from Burkina Faso and either South Africa or Kenya, an unprecedented
      level of intraspecific ITS2 divergence in Anopheles. Taken together, these data
      suggest that the Burkina Faso sample is not An. rivulorum, but rather a cryptic
      taxon within the Funestus Group.

PMID- 10971715
TI  - Microsatellite frequency and size variation in the parthenogenetic parasitic wasp
      Venturia canescens (Gravenhorst) (Hymenoptera: Ichneumonidae).
AB  - Nine genomic libraries of the parthenogenetic wasp Venturia canescens were
      screened for microsatellite loci. In contrast to other Hymenoptera (GT)n and not
      (CT)n, was the predominant repeat category found with 14 kb and 28 kb genomic DNA
      between loci, respectively. Mono- and trinucleotide microsatellites were rarer,
      occurring at frequencies between 231 kb and 589 kb of genome, whilst
      tetranucleotide repeats are scarce, with (ATTC)n and (CCGG)n loci occurring every
      692 kb and 983 kb, respectively, and only one small imperfect (GATA)n locus and
      no (GACA)n loci were revealed. Over 70% of the dinucleotide, and all the
      trinucleotide microsatellites were small (less than eleven repeats), whilst 60%
      to 80% of loci were imperfect. Moreover, very few compound microsatellites and
      only a single association between different microsatellites were observed.

PMID- 10971716
TI  - Molecular cloning and structural analysis of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase of the moth Agrotis ipsilon.
AB  - The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which plays
      a key role in isoprenoid biosynthesis, catalyses the synthesis of mevalonate from
      HMG-CoA. Insects do not synthesize cholesterol de novo, rather mevalonate
      derivatives lead to non-sterol isoprenoids which are essential for development
      and reproduction. In this paper, we describe an HMG-CoA reductase of the moth
      Agrotis ipsilon and we report its expression in fat body, ovary, muscle, brain
      and corpora allata tissues of adult specimens. The analysis of the cDNA reveals
      that it encodes a polypeptide of 833 amino acids (Mr = 89785). Alignments of this
      HMG-CoA reductase from A. ipsilon with the homologous sequences of other
      eukaryotes shows a high degree of conservation in all species studied. Parsimony
      analysis based on these alignments produced dendrograms congruent with the
      current systematic schemes. This suggests that, during eukaryote evolution, HMG
      CoA reductase diversified in parallel with taxonomic splitting.

PMID- 10971718
TI  - Cloning of an aquaporin-like cDNA and in situ hybridization in adults of the
      mosquito Aedes aegypti (Diptera: Culicidae).
AB  - A cDNA encoding a putative water channel protein, aquaporin, was cloned from a
      cDNA library of Aedes aegypti Malpighian tubules. The cDNA encodes a 26.11 kDa
      protein similar to insect aquaporins from Haematobia irritans exigua (Diptera)
      and Cicadella viridis (Homoptera), and to mammalian aquaporin 4. Localization of
      the messenger RNA (mRNA) was performed by in situ hybridization of Malpighian
      tubules and analysed by fluorescence and confocal microscopy. The mRNA was
      localized in tracheolar cells associated with the Malpighian tubules. No signal
      was detected in the Malpighian tubule epithelium. The molecular mechanisms for
      water movement between tissues and tracheoles are not yet elucidated in insects.
      Our results suggest a model to explain fluid movements in tracheoles during
      insect respiration.

PMID- 10971717
TI  - Long PCR improves Wolbachia DNA amplification: wsp sequences found in 76% of
      sixty-three arthropod species.
AB  - Bacteria belonging to the genus Wolbachia are associated with a variety of
      reproductive anomalies in arthropods. Allele-specific polymerase chain reaction
      (= Standard PCR) routinely has been used to amplify Wolbachia DNA from
      arthropods. While testing the two-spotted spider mite Tetranychus urticae and
      other arthropods known to be infected with Wolbachia, Standard PCR frequently
      produced false negatives, perhaps because the DNA from the arthropod host
      interfered with amplification by Taq DNA polymerase. Long PCR, which uses two
      enzymes (Taq and Pwo), consistently amplified Wolbachia DNA and a sensitivity
      analysis indicated that Long PCR was approximately six orders of magnitude more
      sensitive than Standard PCR in amplifying plasmid DNA spiked into insect genomic
      DNA. A survey indicated that 76% of sixty-two arthropod species and two
      subspecies in thirteen orders tested positive for the Wolbachia wsp sequence by
      Long PCR, which is considerably higher than the rate of 16.9% obtained previously
      for the ftsZ sequence using Standard PCR (Werren, J.H., Windsor, D. and Gao, L.
      (1995a) Proc R Soc Lond B 262: 197-204). A subsample of Long PCR products from
      fourteen arthropod species and two subspecies were sequenced, both directly and
      after cloning. Two A- and eleven B-Wolbachia strains were detected and their wsp
      sequences displayed a maximum of 23.7% sequence divergence at this locus. Two new
      groups (named Fus and Ten) were identified in addition to nineteen reported
      earlier (Zhou, W., Rousset, F. and O'Neill, S.L. (1998) Proc R Soc Lond B 265: 1
      7; van Meer, M.M.M., Witteveldt, J. and Stouthamer, R. (1999) Insect Mol Biol 8:
      399-408), because they displayed more than 2.5% sequence divergence from other
      Wolbachia wsp sequences. PCR products from seventeen of twenty-nine (59%)
      arthropod species analysed could not be sequenced directly due to apparent
      infection by multiple Wolbachia strains. The wsp sequences cloned from two such
      species (Plutella xylostella and Trichoplusia ni) indicated both A- and B
      Wolbachia were present in a single individual. Hence, superinfection also may be
      more widespread than the 1.2% incidence previously estimated.

PMID- 10971719
TI  - Molecular cloning and characterization of a metal responsive Aedes aegypti
      intestinal mucin cDNA.
AB  - We have isolated a cDNA from Aedes aegypti that is transcribed in the larval
      midgut in response to metal exposure, and in the adult female midgut in response
      to iron or cadmium exposure, or a blood meal. The cDNA encodes a protein,
      designated Aedes aegypti intestinal mucin 1 (AEIMUC1), which has similarities
      with invertebrate intestinal mucins and peritrophins, and vertebrate mucins.
      Proline, serine and threonine comprise 30% of the amino acid composition of
      AEIMUC1, a characteristic of mucins. AEIMUC1 contains three cysteine-rich
      domains, two of which flank a proline/serine/threonine-rich domain, a feature
      shared by many mucin genes. This is the first report on the isolation of a metal
      responsive gene from an aquatic insect.

PMID- 10971720
TI  - Sequence and evolution of a hexamerin from the ant Camponotus festinatus.
AB  - In the ant Camponotus festinatus, two different hexamerins accumulate stage
      specifically during the late larval period and at various times in adults. These
      hexamerins serve as storage proteins and play important roles in brood
      nourishment and colony founding. We report an analysis of the cDNA sequence of C.
      festinatus hexamerin 2 (CfeHex2). The native protein contains 732 amino acids,
      which are moderately enriched in aromatic amino acids, aspartate and asparagine.
      Phylogenetic analyses show a close relationship of CfeHex2 to a putative toxin of
      the braconid wasp, Bracon hebetor. The divergence of Formicidae and Braconidae
      hexamerins was calculated to have begun 187 MYA, an estimate consistent with
      currently accepted phylogeny of insect orders.

PMID- 10971721
TI  - Microsatellite DNA markers reveal genetic differentiation among populations of
      Glossina palpalis gambiensis collected in the agro-pastoral zone of Sideradougou,
      Burkina Faso.
AB  - Intraspecific genetic variability of Glossina palpalis gambiensis in the area of
      Sideradougou, Burkina Faso, was studied using polymorphic microsatellite DNA
      markers. This genetic study was combined with other epidemiological information
      on the same tsetse: bloodmeal identification, dissection of tsetse and molecular
      characterization of the trypanosomes detected. There was significant genetic
      differentiation among flies caught only a few kilometers apart, within the same
      riverine habitat. These distinct subpopulations were also differentially infected
      by trypanosomes. In part of the study area, a Factorial Correspondence Analysis
      undertaken on the genotypes allowed us to detect a Wahlund effect, suggesting the
      presence of tsetse originating from different source populations coming from two
      distinct drainage systems. The apparent structuring of populations of G. palpalis
      gambiensis is discussed relative to appropriate strategies to control African
      Trypanosomosis.

PMID- 10971722
TI  - The digital imaging system and dermatology.

PMID- 10971723
TI  - Androgenetic alopecia and microinflammation.

PMID- 10971724
TI  - Medical management of male pattern hair loss.

PMID- 10971725
TI  - Nehushtan: on parchment and publications.

PMID- 10971726
TI  - HLA in alopecia areata.
AB  - BACKGROUND: The aim of this study was to investigate the human leukocyte antigen
      (HLA) characteristics of Turkish alopecia areata patients, and the correlation of
      the HLA profile with age of onset, severity and duration of the disease, presence
      of ophiasis, and family history. METHODS: A total of 88 patients with alopecia
      areata, alopecia totalis, or alopecia universalis were compared with 100 healthy
      controls. HLA typing was performed by the Terasaki microlymphocytotoxicity
      method. RESULTS: The frequency of HLA-A1, HLA-B62(15), HLA-DQ1, and HLA-DQ3 was
      significantly higher in patients than in controls. HLA-DR16 was significantly
      less common in patients than in the control group, and we concluded that this
      allele might have a protective role for alopecia areata. Juvenile onset and
      severe involvement were related with HLA-Cw7 and HLA-DR1, respectively. The HLA
      profile was independent of the existence of long-standing disease, presence of
      ophiasis, and a positive family history. CONCLUSIONS: In HLA-alopecia areata
      association, ethnic differences may play a role.

PMID- 10971727
TI  - In vivo delayed-type hypersensitivity in 109 patients with vitiligo.
AB  - BACKGROUND: Although the etiology of the depigmentation disorder vitiligo is
      still not completely understood, many investigators believe that an autoimmune
      reaction may play a major role. In this regard, T-lymphocyte-mediated immunity
      has been implicated frequently in the pathogenesis of the disease. Most studies
      have applied in vitro testing of cell-mediated immunity, however, rather than in
      vivo measurements. Therefore, our study was undertaken to define the cutaneous
      delayed-type hypersensitivity (DTH) in vivo reaction in association with the
      absence/presence of serum thyroid autoantibodies, which are a good representative
      marker for autoimmunity in patients with vitiligo. METHODS: DTH was evaluated in
      the normal pigmented skin of 109 vitiligo patients (29 men and 80 women) and in
      the depigmented skin of 27 of this group (5 men and 22 women) using the dermal
      application of seven common recall antigens together with a negative control.
      Individuals were considered to be hypoergic if the DTH sum score was </= 5 mm in
      women or </= 10 mm in men, or if they responded to only one or two antigens.
      RESULTS: The mean sum score was 10.2 +/- 8.4 with an average of 2.3 +/- 1.6
      positive reactions in depigmented skin vs. a sum score of 12.4 +/- 9. 0 with an
      average number of 2.6 +/- 1.6 positive reactions in normal pigmented skin. There
      was no statistically significant difference between depigmented and normal
      pigmented skin using the paired t-test (P > 0.05). Further evaluation of these
      data showed no significant correlation between the presence of thyroid
      autoantibodies as well as selected clinical parameters and an aberration in
      cutaneous DTH. CONCLUSIONS: In contrast to earlier reports, our in vivo studies
      of cutaneous DTH reactions revealed no clinically significant aberrant cellular
      immunity in this patient group. These results indicate that the immune reaction
      in vitiligo may be only a secondary event in the pathogenesis of the disease.

PMID- 10971728
TI  - Cathepsin D expression in early cutaneous malignant melanoma.
AB  - BACKGROUND: The aspartic proteinase cathepsin D is believed to be associated with
      proteolytic processes leading to the invasion and seeding of tumor cells. An
      association between cathepsin D tissue concentration and aggressiveness of tumors
      has been detected in different cancer types, as well as in metastatic melanoma.
      METHODS: The concentration of cathepsin D was measured immunoradiometrically
      (ELSA-CATH-D kit, CIS Bio International) in the cytosols of 51 primary cutaneous
      melanomas (with Breslow index < 4 mm) to estimate the tissue concentrations of
      cathepsin D in early cutaneous melanoma. RESULTS: A significantly elevated
      concentration of cathepsin D was measured in the tumor cytosols as compared to
      adjacent normal tissue (44.2 vs. 14.7 pmol/mg of total protein, P < 0.001).
      CONCLUSIONS: Our results indicate that cathepsin D is expressed at high levels by
      melanoma cells. The extremely high expression of cathepsin D in two of our
      patients, with later progression of the disease over a 42-month follow-up period,
      suggests a possible correlation between the cathepsin D tissue concentration and
      the prognosis of primary cutaneous malignant melanoma.

PMID- 10971729
TI  - Dendritic epidermal gamma/delta T cells (DETC) activated in vivo proliferate in
      vitro in response to Mycobacterium leprae antigens.
AB  - BACKGROUND: gamma/delta T-cell receptor (TCR)+ dendritic epidermal T cells (DETC)
      are part of a primitive defense system in the skin; they are capable of
      responding only to a limited number of antigens. The aim of the present study was
      to test whether DETC can proliferate in vitro in response to antigens of
      Mycobacterium leprae. METHODS: DETC were obtained from CBA mouse ear skin by
      trypsinization and Histopaque gradient centrifugation. The resulting epidermal
      cell suspension contained up to 20% DETC, as analyzed by the fluorescence
      activated cell sorter (FACS) after staining with anti-Thy-1 or anti-gamma/delta
      TCR monoclonal antibodies (mAbs). The freshly isolated cells, or DETC cultured up
      to 4 weeks with interleukin-2 (IL-2), were exposed in vitro for up to 6 days to
      varying doses of the following M. leprae antigens: (1) integral (live) M. leprae
      bacilli; (2) Dharmendra antigen; and (3) PGL-1 (phenolic glycolipid of M.
      leprae). The DETC response was assessed by tritiated thymidine (3H-TdR)
      incorporation. RESULTS: The freshly isolated DETC, or DETC cultured up to 4 weeks
      with IL-2, did not respond significantly to any of the M. leprae antigens,
      although at the same time they were able to respond vigorously to concanavalin A
      (Con A), as positive control. If, however, DETC were isolated from skin, painted
      7 days before with croton oil (10 microL/cm2 to cause irritant dermatitis, they
      were able to respond to all M. leprae antigens by a 3-4-fold incrase in the 3H
      TdR uptake. The most effective stimulator was a 1 : 1 mixture of Dharmendra and
      PGL-1 (0. 01 microg/mL), which was as effective as 10-fold higher doses of either
      antigen alone. Cell counts confirmed that increased DNA synthesis was associated
      with cell proliferation. Experiments employing alpha/beta-TCR CBA murine spleen
      cells and epidermal cell suspension treated with anti-gamma/delta or
      antialpha/beta mAbs + C' proved that only the gamma/delta DETC were the responder
      cells to M. leprae antigens. CONCLUSIONS: The results suggest that activation of
      DETC in vivo may make them responsive to M. leprae antigens. A significant
      increase in the number of class II major histocompatibility complex (MHC)
      positive, nondendritic cells was observed in the croton oil-treated epidermis. We
      hypothesize that croson oil-induced upregulation of class II MHC expression,
      which endows epidermal cells with antigen-presenting capabilities, might be an
      important factor in vivo in delivering an immunogenic signal to resident DETC in
      the skin.

PMID- 10971730
TI  - Immunoperoxidase technique for detecting spirochetes in tissue sections:
      comparison with other methods.
AB  - BACKGROUND: With the increasing incidence of human immunodeficiency virus (HIV)
      infection and immunosuppressive therapy, the incidence of syphilis has been
      increasing. Given the fact that the above conditions may mask or obscure the
      usual clinical signs and symptoms of syphilis, a means of enhanced detection is
      essential. AIMS METHODS: The purpose of this study was to determine whether an
      immunoperoxidase method using an antibody against treponemes would increase the
      sensitivity and specificity of diagnosis in biopsies of patients with secondary
      syphilis. This was compared to serology and silver stain in cases of known
      syphilis. RESULTS: Immunoperoxidase for treponemes was at least as sensitive
      (9/10) as pathology (9/10), and more sensitive than conventional silver stain
      (6/10) or serology (7/10). CONCLUSIONS: In those equivocal cases of secondary
      syphilis, where confirmation is essential, immunoperoxidase for treponemes may be
      a useful adjunct.

PMID- 10971731
TI  - Milia en plaque: a new site.
AB  - A 35-year-old Kuwaiti field worker presented with a history of an asymptomatic,
      erythematous plaque on the right side of the nasal bridge. It soon extended to
      the malar area, being studded with multiple yellowish papules (Fig. 1). He denied
      any history of photosensitivity, drug intake, local trauma, topical applications,
      or ionizing radiations to that area. Examination revealed an erythematous, 1.5 x
      3 cm plaque on the right nasal fold, extending to the malar area, overlain by a
      group of tiny yellowish papules (15-20 in number). He also had a few discrete
      milia on the right cheek. The histology (Fig. 2) revealed multiple keratin-filled
      cysts, surrounded by a dense lymphocytic infiltrate, findings consistent with
      milia; 0.05% tretinoin was prescribed twice daily for 1 month without
      improvement; minocycline, 100 mg daily, was then employed, and at 1 month of
      follow-up there was a significant decrease in erythema and milia count.

PMID- 10971732
TI  - Perianal Crohn's disease.
AB  - A 13-year-old girl with a history of 4 months of perianal skin lesions is
      described. Physical examination revealed three 0.5 I 1-cm red, swollen, fleshy,
      skin tags extending from the perianal area to the perineum (Fig. 1). The patient
      reported intermittent fever, diarrhea, and abdominal pain, and her body weight
      was below the third percentile for her age. Laboratory studies showed an
      erythrocyte sedimentation rate of 101 mm/h; hematocrit of 26%; white blood cell
      count of 9800/mm3; serum iron of 15 mg/L (normal value (NV), 60-160 mg/L);
      ferritin of 43.4 microg/L (NV, 12-150 microg/L); transferrin of 203 mg/100 mL
      (NV, 200-400 mg/100 mL); transferrin saturation of 6% (NV, 20-50%);
      hypoalbuminemia; negative purified protein derivative (PPD), cytomegalovirus
      (CMV), human immunodeficiency virus (HIV), venereal disease research laboratory
      (VDRL), and antinuclear antibody tests; and Toxoplasma titers of 1/16, Van de
      Kamer 1.67 g/day. A barium examination revealed marked irregularity of the
      descending colon, and a colonoscopy showed uneven areas of mucosal edema and
      pseudopolyps in the transverse and descending colon, associated with irregular
      thickening and stenosis. Histopathologically, large intestine and skin lesions
      consisted of noncaseating epithelioid and giant cell granulomas (Fig. 2).
      Cultures for acid-fast bacilli and fungi were negative, and under polarized light
      no foreign bodies were seen. Treatment with metronidazole (250 mg three times a
      day), prednisone (0.5 mg/kg/day), and acetylsalicylic acid (75 mg/kg/day) was
      moderately effective. Vitamin, folic acid, and iron supplements were also added.

PMID- 10971733
TI  - Detection of Epstein-Barr virus DNA in a patient with Kimura's disease.
AB  - An 80-year-old man, with a past medical history of senile dementia, presented
      with a 6-month history of a solitary, gradually enlarging tumor, located on his
      chin. A squamous cell carcinoma had been surgically excised 30 years previously
      in the same location. Physical examination revealed an erythematous, well-defined
      plaque of 3 cm in diameter, located on the chin (Fig. 1). The submandibular lymph
      nodes were enlarged. Squamous cell carcinoma and primary cutaneous lymphoma were
      considered. Relevant laboratory findings were as follows: white blood cell count,
      5.600/microL; eosinophils, 1000/microL; gammaglobulin, 2.4 g/dL; lactate
      dehydrogenase, 343 IU/L; and immunoglobulin G (IgG) antibodies to Epstein-Barr
      virus (EBV) positive (at 1 : 128 serum dilution), with negative IgM. Skin and
      lymph node biopsies were performed. Histopathologic study of the cutaneous
      specimen revealed a heavy lymphoid infiltrate with numerous lymphoid follicles,
      with prominent germinal centers involving the subcutaneous fat as well as the
      deep dermis and muscular fascia. Some germinal centers showed folliculolysis. The
      lymphoid follicles were surrounded by fibrous tissue. The interfollicular
      infiltrate was rich in plasma cells and eosinophils that formed scattered
      eosinophilic microabscesses. Thin-walled vessels were numerous and prominent, but
      with no epithelioid or vacuolated endothelial cells (Fig. 2). Histopathology of a
      lymph node biopsy specimen showed reactive lymphoid follicle hyperplasia, with
      prominent eosinophilic infiltrates in both follicular and interfollicular areas.
      Eosinophilic deposits and polykaryocytes of Warthin-Finkeldey type were seen in
      the germinal centers. The paracortical area showed vascular proliferation.
      Polymerase chain reaction (PCR) for the detection of specific sequences of EBV
      from routinely processed paraffin-embedded material was carried out under the
      conditions and with the same set of primers as described previously in detail
      (Tenorio A, Echevarria JE, Casas E et al. J Virol Methods 1993; 44: 261-269). DNA
      samples were confirmed to be amplifiable with PCR primers specific for a
      conserved region of the human beta-globin gene. Every sample was tested at least
      twice for EBV DNA and beta-globin gene. One sample from one skin lesion of the
      patient, with confirmed diagnosis of Kimura's disease, and 10 samples from normal
      skin biopsies retrospectively collected from other patients in archival files of
      our department were tested. Only the patient's specimen tested positive to EBV.
      The amplified product of EBV was analyzed using DNA sequencing and confirmed the
      results obtained. The patient received radiotherapy at doses of 35 Gy.
      Nevertheless, the tumor enlarged to reach twofold its original size 1 month
      later. Due to the physical status of the patient, no further treatments were
      considered, but the disease remained stable over the following 3 years.

PMID- 10971734
TI  - Toxic epidermal necrolysis following combination of methotrexate and trimethoprim
      sulfamethoxazole.
AB  - A 15-year-old boy with T-cell acute lymphoblastic leukemia (ALL) (FAB L1),
      diagnosed in 1995, received combination chemotherapy consisting of 6 weeks of
      induction (vincristine, epirubicin, L-asparaginase, prednisolone) and 2 weeks of
      consolidation (cytosine arabinosides, etoposide). After achieving remission, for
      further maintenance of remission, he was treated with 14 cycles of intensive
      chemotherapy consisting of 6-MP, 10 mg/kg orally on the first 4 days, and
      cyclophosphamide, 1200 mg/m2, vincristine, 1.5 mg/m2, epirubicin, 15 mg/m2, and
      cytosine arabinoside, 40 mg/m2, intravenously on days 4, 11, 39, and 40,
      respectively. On day 18 of each cycle, he received intravenous methotrexate (MTX)
      infusion in a total dose of 150 mg/m2 plus oral leucovorin (30 mg/m2 ) rescue 36
      h after starting MTX therapy. In addition, oral trimethoprim-sulfamethoxazole was
      given regularly to prevent Pneumocystis carinii infection. The patient achieved
      remission during the first course of treatment, but 8 months later the disease
      relapsed. He then received four doses of MTX (800 mg intravenously) plus
      leucovorin rescue in the following 4 months. During the last MTX therapy, small
      hemorrhagic bullae were found on the lateral side of the right ankle, but
      subsided after a few days. Due to partial remission of the disease, he was
      admitted again in January 1999 for high-dose MTX therapy. An initial hemogram on
      admission revealed hemoglobin 7.2 g/dL, white cell count 15,200/mm3, platelet
      count 153/mm3, blood creatinine 0.5 mg/dL, and alanine leucine aminotransferase
      (ALT) 20 U/L. He received 8500 mg of MTX (5000 mg/m2 ) as a continuous
      intravenous infusion for 24 h. Thirty-six hours after the start of MTX infusion,
      leucovorin (30 mg, intravenous) rescue was initiated every 6 h for 3 days.
      Another preventive measure to cover MTX toxicity included aggressive intravenous
      fluid replacement (4 L/m2 /day) and the addition of 25 meq/L sodium bicarbonate
      to the intravenous fluid to alkalinize the urine. Concurrent medication included
      6-MP (50 mg) once daily and trimethoprim-sulfamethoxazole (120 mg, 600 mg) twice
      daily every other day. Plasma MTX levels were 52.36 micromol/L 24 h after MTX
      infusion, 1.87 micromol/L after 48 h, 0.57 micromol/L after 72 h, and 0.41
      micromol/L after 96 h. These indicated delayed MTX plasma clearance. The blood
      creatinine level was mildly elevated from 0.5 mg/dL to 0.7 mg/dL. Thirty-six
      hours after the administration of MTX, the patient developed an erythematous
      painful swelling on the right middle finger. The erythema, with subsequent large
      bulla formation, progressed to all the fingers, toes, palms, and the soles of the
      feet. Some erythematous to hemorrhagic papules also appeared on the bilateral
      elbows. Subsequently, diffuse tender erythema with extensive erosions and focal
      tiny pustules developed on the back, abdomen, proximal extremities, and face
      (Fig. 1a,b). A positive Nikolsky's sign was also present. A biopsy specimen of
      the right dorsal hand lesion revealed parakeratosis, detached acanthotic
      epidermis with scattered necrotic keratinocytes, dyskeratotic cells and nuclear
      atypia, neutrophilic exocytosis, and many neutrophils in the papillary dermis
      (Fig. 2). The skin condition deteriorated rapidly. Toxic epidermal necrolysis
      like lesions involved 90% of the total body surface on the fifth day after MTX
      infusion. Mucositis, diarrhea, involuntary tremor, fever, and chills were noted.
      The patient was then sent to the burn unit for intensive skin care. Ten days
      after MTX therapy, profound agranulocytosis and thrombocytopenia (white cell
      count 100/mm3, platelets 14,000/mm3, and hemoglobin 5.6 g/dL) were found. The
      patient was then started on granulocyte colony stimulation factor (G-CSF, 5
      microg/kg/day), but his general condition deteriorated rapidly and he died 6 days
      later due to septic shock and multiple organ failure.

PMID- 10971735
TI  - Use of high-dose methylprednisolone pulse therapy in patients with progressive
      and stable vitiligo.
AB  - BACKGROUND: Although there are several treatment options available for patients
      with generalized vitiligo, their efficacy is still a matter of debate. Although
      shown to be effective, corticosteroids applied either systemically or topically
      carry the risk of significant side-effects in long-term therapy. We evaluated the
      effectiveness of intravenous methylprednisolone (8 mg/kg body weight)
      administered on three consecutive days in patients with generalized vitiligo.
      MATERIALS AND METHODS: A total of 14 patients with progressive or static vitiligo
      were included in a prospective, open, clinical study. RESULTS: Eighty-five per
      cent of the patients presenting with progressive disease showed cessation of
      disease progression after the infusion therapy. Repigmentation was observed in
      71% of patients with progressive vitiligo. None of the six patients presenting
      with static disease showed any repigmentation in response to this form of
      treatment. The therapy was well tolerated in all but one patient who developed
      intermittent arterial hypertension during therapy. CONCLUSIONS: High-dose
      glucocorticoid pulse therapy may represent a therapeutic option in patients with
      generalized progressive vitiligo, and should be further evaluated in a
      prospective, randomized, clinical trial.

PMID- 10971736
TI  - Does immune serum globulin confer protection against skin diseases?
AB  - BACKGROUND: Following a case of serologically proven hepatitis A in a food
      handling worker serving several military bases in the same vicinity, the entire
      military population was vaccinated with immune serum globulin (ISG). OBJECTIVE:
      To evaluate the effectiveness of ISG in preventing skin disease. METHODS: The
      data for this study were drawn from the military archives of the Medical Corps.
      The population of the bases was followed for a period of 3 months after
      immunization. Rates of selected skin diseases were compared with those of a
      nearby base during the same period, and with those in the population of the same
      bases a year earlier. RESULTS: The rates of several skin diseases (bacterial skin
      infections, dermatitis and eczema, fungal infections, acne, warts, nail
      disorders, and nonspecific skin diseases) among the vaccinated population were
      significantly lower when compared to the historical control group and to the
      contemporary control group of the nearby base. CONCLUSIONS: ISG provides a
      protecting effect for skin diseases, especially those of infectious origin.

PMID- 10971737
TI  - The discovery of the hematoblast by Carl Heitzmann (1836-1896) in 1872.

PMID- 10971739
TI  - Synovial chondromatosis: the possible role of FGF 9 and FGF receptor 3 in its
      pathology.
AB  - Primary synovial chondromatosis (PSC) is a rare disorder of the synovium typified
      by cartilaginous nodule formation within the synovial membrane. Fibroblast growth
      factor receptor 3 (FGFR3) is a recently described specific marker of mesenchymal
      precartilaginous stem cells. Expression patterns of FGFR3 and its specific
      ligand, fibroblast growth factor 9 (FGF 9), were evaluated both in situ and in
      cell cultures. Histologically, cells at the periphery of the cartilage nodules
      express FGFR3 and PCNA (proliferating cell nuclear antigen). Elevated levels of
      FGF 9, its specific ligand, have been found in synovial fluids of patients with
      synovial chondromatosis. Synoviocytes but not chondrocytes from affected patients
      express FGF9 in culture. This pattern is absent in normal synovium and cartilage.
      Downregulation of FGF9 may provide a possible nonoperative therapy for PSC.

PMID- 10971740
TI  - 2.5 kDa and 5.0 kDa heparin fragments specifically inhibit microvessel sprouting
      and network formation in VEGF165-mediated mammalian angiogenesis.
AB  - Tumour growth is angiogenesis dependent. Thrombosis and thromboembolism are very
      common in cancer patients. These patients are often treated with heparin as an
      anti-coagulant. Many tumour angiogens, including VEGF165, and endogenous anti
      angiogenesis factors bind heparin tightly. Using the non-surgical mesenteric
      window angiogenesis assay, we studied in detail the systemic effect of heparin
      fractions with a mean MW of 2.5, 5.0 and 16.4 kDa on the microvessel sprouting
      and network formation in angiogenesis mediated by VEGF165 in rats. The
      microvessel network was assessed objectively in terms of the number and lengths
      of segments (the distance between two successive branching points), the number of
      branching points, the degree of tortuosity, the index of interconnecting loop
      formation, the index of intersection, as well as the number and lengths of
      sprouts. Compared with the saline control, the 2.5 kDa fraction significantly
      shortened the microvessel sprouts and the microvessel segments but increased the
      microvessel tortuosity in statistical terms; the 5.0 kDa fraction statistically
      significantly shortened the sprouts, decreased the number of segments and the
      number of microvessel branching points; whereas the 16.4 kDa fraction
      statistically significantly elongated the longest segments. Moreover,
      statistically significant differences were found between the three heparin
      fractions in terms of microvessel tortuosity (2.5 vs. 16.4 kDa), index of loop
      formation (5.0 vs. 2.5 + 16.4 kDa) and index of intersection (5.0 vs. 16.4 kDa).
      These findings demonstrate that heparin fragments size-specifically inhibit
      microvessel sprouting and network formation in VEGF165-mediated angiogenesis. As
      VEGF165 is a potent angiogen in human tumours, we suggest that heparin enriched
      in 2.5 kDa species and 5.0 kDa species especially should be exploited as a
      combined anti-coagulant and specific adjuvant anti-angiogenic agent in cancer
      patients who require anti-coagulant therapy.

PMID- 10971738
TI  - The extracellular matrix can regulate vascular cell migration, proliferation, and
      survival: relationships to vascular disease.
AB  - The extracellular matrix (ECM) of the normal artery wall is a collection of
      fibrous proteins and associated glycoproteins embedded in a hydrated ground
      substance of glycosaminoglycans and proteoglycans. These distinct molecules are
      organized into a highly ordered network that are closely associated with the
      vascular cells that produce them. In addition to providing the architectural
      framework for the artery wall that imparts mechanical support and
      viscoelasticity, the ECM can regulate the behaviour of vascular cells, including
      their ability to migrate, proliferate and survive injury. The composition of the
      ECM is different within intimal lesions of atherosclerosis, which are composed of
      monocytes and lymphocytes from the circulation and smooth muscle cells (SMC) that
      migrate from the media to the intima (Ross 1993, 1999), and these differences may
      contribute to the altered phenotype of vascular cells within lesions. This review
      will briefly outline the ECM changes observed in atherosclerosis and restenosis
      and the potential relationship of these changes to altered vascular cell
      functions.

PMID- 10971742
TI  - Immunopathology of in situ seminoma.
AB  - In this study of the seminomatous human testis the composition, activity and
      apoptosis of lymphocytes infiltrating the immune-privileged seminiferous tubules
      with in situ seminoma were studied by immunohistochemistry and DNA fragmentation
      detection. Likewise the lymphocytes infiltrating the invasive seminomas were
      studied. The study showed equal numbers of CD4+ and CD8+ T cells and B cells,
      about 30% of the cells. Very few T gamma/delta and NK cells were present. The
      activity in terms of IL-2-R, FasL and perforin expression was low. Apoptosis of
      the lymphocytic cells was limited. No differences were observed between the
      lymphocytes in seminiferous tubules with in situ seminoma and the lymphocytes in
      invasive tumours. The study suggests that either specifically committed
      lymphocytes are not present or, if present, immune-suppressing mechanisms in
      addition to FasL may be working.

PMID- 10971741
TI  - Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent
      metalloproteinases, causes deviation of the cytokine profile towards type-2 in
      experimental pulmonary tuberculosis in Balb/c mice.
AB  - BB-94 (batimastat) is a broad- spectrum hydroxamic acid-based zinc
      metalloproteinase inhibitor that inhibits both the matrix metalloproteinases
      (MMP) and members of the ADAM family of enzymes such as Tumour Necrosis Factor
      alpha Cleaving Enzyme (TACE). These enzymes are involved in the regulation of
      inflammatory processes in tuberculosis. Balb/c mice infected with M. tuberculosis
      via the intratracheal route were treated with BB-94 for 1 month, starting on the
      day of infection. Immunohistochemistry, semiquantitative RT-PCR and ELISA assays
      for cytokines revealed a deficit in IL-1 and IL-2 expression and a premature bias
      towards IL-4 expression, accompanied by a delay in granuloma formation and more
      rapid progression of disease in BB-94-treated animals. This situation corrected
      itself after the drug was withdrawn at 28 days. In contrast, when BB-94 was
      administered only after 1 month there were no significant changes apart from the
      presence of amyloid, and a paradoxically increased expression of IL-1alpha. These
      results cast light on mechanisms of immunity in tuberculosis and also indicate
      that in patients treated with similar broad-spectrum MMP inhibitors there may be
      a risk of inappropriate deviation of some immune responses towards a Type-2
      cytokine profile.

PMID- 10971744
TI  - Accumulation of amyloid-beta protein in exocrine glands of transgenic mice
      overexpressing a carboxyl terminal portion of amyloid protein precursor.
AB  - Amyloid-beta protein (Abeta) and its precursor (betaPP) play important roles in
      the pathogenesis of Alzheimer disease and inclusion-body myositis. In humans,
      Abeta deposits are found in brain, skeletal muscle, and skin. Therefore, we have
      investigated possible Abeta deposits in multiple tissues of two transgenic mouse
      lines overexpressing the signal plus Abeta-bearing 99-amino acid carboxyl
      terminal sequences of betaPP under the control of a cytomegalovirus enhancer/beta
      actin promoter. One of the lines developed Abeta-immunoreactive intracellular
      deposits consistently in the pancreas and lacrimal gland, and occasionally in
      gastric, DeSteno's, and lingual glands. Although the Abeta deposits increased
      during ageing and degenerative changes of the tissues were observed, little or no
      extracellular Abeta deposits were observed up to the age of 25 months. These
      lines of transgenic mice are useful for studying the molecular mechanisms of
      development and clearance of intracellular Abeta deposits.

PMID- 10971745
TI  - Cell cholesterol esters and high-density lipoprotein plasma levels during liver
      hyperplasia in choline-fed male and female rats.
AB  - Sexual dimorphism exists in the response of rats to lead nitrate, liver
      hyperplasia occuring earlier and being more pronounced in males. Excess dietary
      choline in females shifted the growth pattern towards that of males. To determine
      whether phosphatidylcholine-induced growth modulations could be related to a
      derangement of cholesterol metabolism, liver accumulation of cholesterol esters
      and plasma lipoprotein patterns were investigated. In males, lead-induced liver
      hyperplasia was associated with increased total cholesterol hepatic content,
      accumulated cholesterol esters and reduced concentration of plasma High Density
      Lipoprotein (HDL) cholesterol. Females were less responsive to the liver
      mitogenic signal of lead nitrate; there was no elevation of cholesterol content
      nor any marked accumulation of cholesterol esters. This is consistent with the
      lack of change in the plasma levels of HDL cholesterol. Continuous choline
      feeding displaced the liver cholesterol ester pattern and plasma HDL cholesterol
      levels in females, and in parallel that of DNA synthesis, towards those of males.
      Choline was not observed to have any effect in males. These results suggest that
      the derangement of phosphatidylcholine metabolism induces growth-related changes
      in cholesterol turnover; they are consistent with the proposal that the
      intracellular content of cholesterol esters may have a role in regulating liver
      growth rates.

PMID- 10971743
TI  - Cigarette smoking, endothelial injury and cardiovascular disease.
AB  - Despite the fact that the epidemiological evidence linking cigarette smoking with
      cardiovascular disease is overwhelming, the precise components of cigarette smoke
      responsible for this relationship and the mechanisms by which they exert their
      effect have not yet been elucidated. There are however, some promising pointers
      as a result of recent developments and this review concentrates on new evidence
      since earlier reviews of this topic. It is now known that the endothelium has a
      vastly more important role than was ever thought to be the case a decade ago. Its
      role in health and disease is increasingly understood, as is the relationship
      between endothelial injury and the development of atherosclerosis. There is
      considerable evidence that cigarette smoking can result in both morphological and
      biochemical disturbances to the endothelium both in vivo and in cell culture
      systems. Cigarette smoke is a complex mixture and only a few components have been
      extensively studied. Nicotine and carbon monoxide are much less damaging than is
      whole smoke. However the free radical components of cigarette smoke have been
      shown to cause damage in model systems. Further work will be necessary to
      consolidate the evidence base but the data reported in this review suggest that
      the free radical components of cigarette smoke may be responsible for the
      morphological and functional damage to endothelium that has been observed in
      model systems.

PMID- 10971746
TI  - Insulin-like growth factor (IGF)-I affects parasite growth and host cell
      migration in experimental cutaneous leishmaniasis.
AB  - While the control or progression of leishmaniasis depends on host immune
      responses, the initial inflammatory process represents a key event. This process
      involves the participation of several cytokines and growth factors induced during
      inflammation as well as factors already present at the site of infection such as
      insulin-like growth factor (IGF)-I. We have previously demonstrated a potential
      role for IGF-I in experimental cutaneous leishmaniasis based on the significant
      increase in lesion size seen in mice injected with Leishmania promastigotes
      preactivated with IGF-I. In the present study we show that preactivation of
      Leishmania (Leishmania) amazonensis promastigotes with IGF-I induces an increase
      in the actual number of parasites at the lesion site from seven days
      postinfection, in addition to a more intense inflammatory infiltrate. There was a
      higher numerical density of polymorphonuclear neutrophils from 3 to 24 h, and of
      mononuclear cells from 48 h of infection onward. A higher density of
      polymorphonuclear neutrophils and mononuclear cells harboring parasites was also
      observed. The most important observation, however, was that more parasites per
      cell were present, revealing that IGF-I appears to favour parasite growth within
      the macrophages. These results strongly suggest an important role for IGF-I in
      the development of cutaneous leishmaniasis, where it influences both the
      inflammatory process and parasite growth.

PMID- 10971747
TI  - Antioxidant status in delayed healing type of wounds.
AB  - This investigation studied the contribution of antioxidants in delaying healing
      in excision cutaneous wounds (8 mm) in diabetic, aged and immunocompromised
      animals. Skin levels of catalase, glutathione (GSH), ascorbic acid (AA) and
      vitamin E in streptozotocin-induced diabetic rat were lower as compared to
      nondiabetics. The 7-d wound tissue of diabetic rats showed an increased vitamin E
      level along with depleted GSH content. In aged rats (18 months old), higher
      levels of skin superoxide dismutase (SOD), glutathione peroxidase (Gpx) and
      thiobarbituric acid reactive substances (TBARS) and lower levels of catalase and
      GSH were found as compared to their values in young rats (3-4 months old). The
      levels of SOD, GPx, catalase, AA, GSH and vitamin E in 7-d wound tissue of aged
      rats were significantly lower in comparison to those in young rats. However,
      TBARS were elevated in these wound tissues. The non-wounded skin of
      immunocompromised (athymic) mice showed lower levels of SOD, catalase, and TBARS
      and higher GSH and GPx levels in comparison to those present in normal mouse
      skin. Surprisingly, the analysis of 7-d wound tissue showed higher levels of SOD,
      catalase, GPx, and GSH and lower TBARS level in athymic mice compared to the
      wound tissue of normal mice. Thus low levels of antioxidants accompanied by
      raised levels of markers of free radical damage play a significant role in
      delaying wound healing in aged rats. In diabetic rats reduced glutathione levels
      may have a contributory role in delaying the healing process. However, in
      immunocompromised mice the antioxidant status following injury showed an adapted
      response.

PMID- 10971748
TI  - Endocrine cells in the denervated intestine.
AB  - This study deals with the effects of myenteric denervation of the proximal
      jejunum on endocrine cell population of the crypt-villus unit, 5 months after
      treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on
      average 100 g were allocated to two groups: the BAC group - the proximal jejunal
      serosa was treated with 2 mM BAC for 30 min, and the control group - treated with
      saline solution (0,9% NaCl). There was a significant reduction in neurone number
      in the jejunal myenteric plexus of the BAC group and the endocrine cell
      population (serotoninergic and argyrophilic cells) was significantly increased in
      this intestine segment. In conclusion, the present findings provide further
      evidence that the myenteric denervation induced by BAC may lead to the
      development of a local imbalance of the neurotransmitters, with a consequent
      induction of enteroendocrine cell (argyrophilic and serotoninergic cells)
      hyperplasia in the crypt and villus.

PMID- 10971750
TI  - Genotypic and phenotypic heterogeneity among lactococci isolated from traditional
      Pecorino Sardo cheese.
AB  - Twenty-nine Lactococcus lactis isolates from one traditional 24 h-old Pecorino
      Sardo cheese were characterized phenotypically, technologically and genotypically
      in order to assess the biodiversity within this wild microbial population. Two
      DNA-based techniques, plasmid profiling and PFGE, were used for the genetic
      typing of the isolates. All 29 isolates were characterized at strain level and
      eight different genotypes were recognized. In addition, by combining the results
      from plasmid profile analysis and PFGE, it was possible to identify closely
      related isolates probably belonging to the same clonal lineage. The dominant
      biotype was identified in the 24 h-old cheese, as were the strains believed to
      act as starters for the curd. Atypical lactococci, able to grow in 6.5% NaCl,
      were isolated. The results suggest that wild bacterial populations should be
      preserved in order to protect the traditional raw milk cheeses, and to select new
      starter strains for the dairy industry.

PMID- 10971751
TI  - The effect of culture growth phase on induction of the heat shock response in
      Yersinia enterocolitica and Listeria monocytogenes.
AB  - The effect of culture growth phase on induction of the heat shock response in
      Yersinia enterocolitica and Listeria monocytogenes, was examined. Exponential or
      stationary preconditioned cultures were heat shocked and survivor numbers
      estimated using selective and overlay/resuscitation recovery techniques. The
      results indicate that prior heat shock induced increased heat resistance in both
      micro-organisms to higher heat treatments. Heat-shocked cells of each micro
      organism were able to survive much longer than non-heat-shocked cells when heated
      at 55 degrees C. The size of the change in heat resistance between heat-shocked
      and non-heat-shocked cells was greatest for exponential cultures (X:X). Results
      indicate that the overall relative thermal resistance of each pathogen was
      dependent on cell growth phase. Stationary cultures (S:S) were significantly (P <
      0.01) more thermotolerant than exponential cultures (X:X) under identical
      processing conditions. Under most conditions, the use of an overlay/resuscitation
      recovery medium resulted in higher D-values (P < 0.05) compared with a selective
      recovery medium.

PMID- 10971749
TI  - Demyelination and axonal dystrophy in alpha A-crystallin transgenic mice.
AB  - Homozygous mice transgenic for alphaA-crystallin, one of the structural eye lens
      proteins, developed hindlimb paralysis after 8 weeks of age. To unravel the
      pathogenesis of this unexpected finding and the possible role of alphaA
      crystallin in this pathological process, mice were subjected to a
      histopathological and immunohistochemical investigation. Immunohistochemistry
      showed large deposits of alphaA-crystallin in the astrocytes of the spinal cord,
      and in the Schwann cells of dorsal roots and sciatic nerves. Additionally,
      microscopy showed dystrophic axons in the spinal cord and digestion chambers as a
      sign of ongoing demyelination in dorsal roots and sciatic nerves. Apart from a
      few areas with slight alphaA-crystallin-immunopositive structures, the brain was
      normal. Because the alphaA-crystallin protein expression appeared in specific
      cells of the nervous system (astrocytes and Schwann cells), the most plausible
      explanation for the paralysis is a disturbance of cell function caused by the
      excessive intracytoplasmic accumulation of the alphaA-crystallin protein. This is
      followed by a sequence of secondary changes (demyelination, axonal dystrophy) and
      finally arthrosis. In conclusion, alphaA-crystallin transgenic mice develop a
      peripheral and central neuropathy primarily affecting spinal cord areas at the
      dorsal side, dorsal root and sciatic nerve.

PMID- 10971752
TI  - Use of flow cytometry to monitor cell damage and predict fermentation activity of
      dried yeasts.
AB  - Viable dried yeast is used as an inoculum for many fermentations in the baking
      and wine industries. The fermentative activity of yeast in bread dough or grape
      must is a critical parameter of process efficiency. Here, it is shown that
      fluorescent stains and flow cytometry can be used in concert to predict the
      abilities of populations of dried bakers' and wine yeasts to ferment after
      rehydration. Fluorescent dyes that stain cells only if they have damaged membrane
      potential (oxonol) or have increased membrane permeability (propidium iodide)
      were used to analyse, by flow cytometry, populations of rehydrated yeasts. A
      strong relationship (r2 = 0.99) was found between the percentages of populations
      staining with the oxonol and the degree of cell membrane damage as measured by
      the more traditional method of leakage of intracellular compounds. There were
      also were good negative relationships (r2 > or = 0.83) between fermentation by
      rehydrated bakers' or wine dry yeasts and percentage of populations staining with
      either oxonol or propidium iodide. Fluorescent staining with flow cytometry
      confirmed that factors such as vigour of dried yeast mixing in water, soaking
      before stirring, rehydration in water or fermentation medium and temperature of
      rehydration have profound effects on subsequent yeast vitality. These experiments
      indicate the potential of flow cytometry as a rapid means of predicting the
      fermentation performance of dried bakers' and wine yeasts.

PMID- 10971753
TI  - The lactoperoxidase system: the influence of iodide and the chemical and
      antimicrobial stability over the period of about 18 months.
AB  - The lactoperoxidase (LP) system is a natural antimicrobial system, the use of
      which has been suggested as a preservative in foods and pharmaceuticals. The
      effect of adding iodide to the LP system, the chemical stability and the change
      in antimicrobial effectiveness during storage was studied. Addition of iodide
      with thiocyanate increased the fungicidal and bactericidal effect against Candida
      albicans, Escherichia coli and Staphylococcus aureus. Pseudomonas aeruginosa
      showed the same inhibition in the LP system with iodide and without iodide.
      Storage of the LP system in completely filled airtight containers for 18 months
      caused a 35% loss of the initial thiocyanate concentration. The antimicrobial
      activity of this LP system was strong enough to kill inocula of 106 cfu ml-1 of
      the four test organisms within 2 h of contact time. During storage of the air
      containing LP system, the concentration of thiocyanate was reduced below
      detection limit within 7 d, the concentrations of hypothiocyanite and hypoiodite
      within 350 d. After 516 d the antimicrobial activity of air-containing LP system
      was strong enough to kill inocula of 106 cfu ml-1 Ps. aeruginosa within 2 h,
      Staph. aureus within 4 h and Candida albicans and E. coli within 1 week of
      contact time.

PMID- 10971754
TI  - The response of a bacterial biofilm community in a simulated industrial cooling
      water system to treatment with an anionic dispersant.
AB  - The effect of a dispersant on the microbial community in a simulated open
      recirculating cooling water system was determined by continuous operation of the
      system over two consecutive periods of 196 and 252 d, respectively. An open
      recirculating cooling water system feeding a modified Robbin's Device with
      synthetic cooling water to simulate the environment of an industrial cooling
      water system was set up. Planktonic and biofilm (mild steel and Nylon(R)) samples
      were taken weekly in 1997 (196-d period) and fortnightly in 1998 (252-d period).
      Each biofilm was scraped off and diluted in 10-ml 1 x phosphate-buffered saline
      (PBS). Serial dilutions were performed and plated onto R2A agar (pH 8.0) to
      obtain the predominant culturable bacteria. The diversity was determined by
      allocating groups according to colony morphology, diameter and colour. Diversity
      was calculated according to the Shannon-Weaver Index. During the first run
      (1997), dispersant was added on day 57 to a final concentration of 15 mg l-1 for
      49 d, stopped for 49 d and dosed at 30 mg l-1 for 41 d. The second run entailed
      adding dispersant to a final concentration of 30 mg l-1 on day 98 for 70 d,
      stopping dosing for 56 d and resuming dosing at 30 mg l-1 for another 28 d. The 2
      year evaluation period demonstrated that the biofilm-removing action of the
      dispersant decreased to a point where it was not effective at all. Our results
      showed that the synthetic dispersant evaluated was only effective initially, but
      was ineffective in controlling biofouling on Nylon, and to a lesser degree on
      mild steel at the recommended (15 mg l-1) as well as at double the recommended
      concentration in the long term. The release of cells from biofilms observed when
      dispersant dosing was terminated, supports the notion that a community attaching
      in the presence of the surface active agent was selected for. The decreased
      efficacy may therefore be due to a selection of strains able to remain attached
      and/or attach in the presence of the dispersant as demonstrated by shifts in the
      biofilm communities on both Nylon and mild steel.

PMID- 10971755
TI  - Molecular identification of wine yeasts at species or strain level: a case study
      with strains from two vine-growing areas of Greece.
AB  - The composition of wine yeast populations, present during spontaneous
      fermentation of musts from two wine-producing areas of Greece (Amyndeon and
      Santorini) and followed for two consecutive years, were studied using a range of
      molecular techniques. Internal Transcribed Spacer (ITS) ribotyping was
      convincingly applied for yeast species identification, proving its usefulness as
      a reliable tool for the rapid characterization of species composition in yeast
      population studies. Restriction Fragment Length Polymorphism (RFLP) of
      mitochondrial DNA (mtDNA) was shown to be a convenient criterion for the
      detection of intraspecies genetic diversity of both Saccharomyces and non
      Saccharomyces isolate populations. Similarly, polymorphism of amplified delta
      interspersed element sequences provided an additional criterion for S. cerevisiae
      strain differentiation. Comparative analysis of S. cerevisiae genetic diversity,
      using mtDNA restriction patterns and delta-amplification profiles, showed a
      similar discriminative power of the two techniques. However, by combining these
      approaches it was possible to distinguish/characterize strains of the same
      species and draw useful conclusions about yeast diversity during alcoholic
      fermentation. The most significant findings in population dynamics of yeasts in
      the spontaneous fermentations were (i) almost complete absence of non
      S.cerevisiae species from fermentations of must originating from the island
      Santorini, (ii) a well recorded strain polymorphism in populations of non
      Saccharomyces species originating from Amyndeon and (iii) an unexpected
      polymorphism concerning S. cerevisiae populations, much greater than ever
      reported before in similar studies with wine yeasts of other geographical
      regions.

PMID- 10971756
TI  - Biological and molecular characterization of a two-peptide lantibiotic produced
      by Lactococcus lactis IFPL105.
AB  - The lactic acid bacterium Lactococcus lactis IFPL105 secretes a broad spectrum
      bacteriocin produced from the 46 kb plasmid pBAC105. The bacteriocin was purified
      to homogeneity by ionic and hydrophobic exchange and reverse-phase
      chromatography. Bacteriocin activity required the complementary action of two
      distinct peptides (alpha and beta) with average molecular masses of 3322 and 2848
      Da, respectively. The genes encoding the two peptides were cloned and sequenced
      and were found to be identical to the ltnAB genes from plasmid pMRC01 of L.
      lactis DPC3147. LtnA and LtnB contain putative leader peptide sequences similar
      to the known 'double glycine' type. The predicted amino acid sequence of mature
      LtnA and LtnB differed from the amino acid content determined for the purified
      alpha and beta peptides in the residues serine, threonine, cysteine and alanine.
      Post-translational modification, and the formation of lanthionine or
      methyllanthionine rings, could partly explain the difference. Hybridization
      experiments showed that the organization of the gene cluster in pBAC105
      responsible for the production of the bacteriocin is similar to that in pMRC01,
      which involves genes encoding modifying enzymes for lantibiotic biosynthesis and
      dual-function transporters. In both cases, the gene clusters are flanked by IS946
      elements, suggesting an en bloc transposition. The findings from the isolation
      and molecular characterization of the bacteriocin provide evidence for the
      lantibiotic nature of the two peptides.

PMID- 10971757
TI  - Potentially pathogenic vibrios in brackish waters and mussels.
AB  - Water and mussel samples were collected from two brackish lakes, used as mussel
      farms, at different times of the year, for the quantitative analysis of Vibrio
      spp. and for the isolation of potentially pathogenic species. The isolates
      underwent cultural and biochemical tests selected for rapid identification.
      Glucose oxidizing-fermenting and O/129 sensitive strains were distinguished on
      the basis of the following tests: sucrose and cellobiose utilization, sulphatase
      activity and polymyxin B resistance performed, respectively, on TCBS, CPC and SPS
      media. Responses to the presence of beta-galactosidase, salt requirement and
      growth on triple sugar iron medium were also added. A total of 125 from 152
      isolates were referred to the species Vibrio fluvialis (55 strains), V.
      alginolyticus (40), V. parahaemolyticus (11), V. vulnificus (10) and V. mimicus
      (9). The remaining 27 isolates were not identified. The isolation of potentially
      pathogenic vibrios from cultivated mussels is a risk for health of people
      consuming raw seafood. Therefore, a long-term monitoring programme should also
      include the search for these bacterial species.

PMID- 10971758
TI  - A survey of the enterococci isolated from an artisanal Italian goat's cheese
      (semicotto caprino).
AB  - Enterococci were isolated from semicotto caprino cheese, a traditional cheese
      produced in Southern Italy: they were a significant part of the microbial
      population of this cheese, confirming the importance of the presence of these
      micro-organisms during cheese-making and ripening. They were also identified and
      studied for their phenotypic and genotypic characteristics: Enterococcus faecalis
      and Ent. faecium were the most frequently isolated species, followed by Ent.
      durans, Ent. hirae and Ent. gallinarum. None of the isolates showed lipolytic
      activity, whereas they were characterized by a relevant proteolytic activity as
      well as an antagonistic activity towards Listeria innocua. One strain of Ent.
      gallinarum showed a low-level resistance to vancomycin, while six out of the 79
      Ent. faecalis strains possessed beta-haemolysis reaction. The highest acidifying
      potential in skim milk was obtained by Ent. faecalis isolates. Thirty
      enterococcal strains representative of the different species at different
      ripening times were analysed by means of RAPD-PCR, and revealed species-specific
      profiles for all the considered species.

PMID- 10971759
TI  - Susceptibility testing: inoculum size dependency of inhibition using the Colworth
      MIC technique.
AB  - The minimum inhibitory concentration, MIC, is an accepted and well used criterion
      for measuring the susceptibility of organisms to inhibitors. Many factors
      influence the MIC value obtained, including temperature, inoculum size and type
      of organism. A modification of the method developed in this laboratory to obtain
      inhibition profiles of antimicrobials was used to examine the effect of inoculum
      size on the degree of inhibition observed with respect to inhibitor
      concentration. The data obtained enabled the production of an empirical model of
      inhibition, based on a Gompertz function, relating the level of growth observed
      to both the inoculum size and concentration of the inhibitor. The inoculum size
      dependencies of phenethyl alcohol, phenoxyethanol, p-chloro-m-cresol, trichloro
      phenol, thymol and dodecyltrimethylammmonium bromide against Staphylococcus
      aureus were obtained.

PMID- 10971760
TI  - Isolation and characterization of a protease from Pseudomonas fluorescens RO98.
AB  - Pseudomonas fluorescens RO98, a raw milk isolate, was inoculated into McKellar's
      minimal salts medium and incubated at 25 degrees C for 48 h to allow production
      of protease. A zinc-metalloacid protease was purified from the cell-free
      concentrate by anion exchange and gel filtration chromatography. The purified
      protease was active between 15 and 55 degrees C, and pH 4.5 and 9.0, and was
      stable to pasteurization. The enzyme had pH and temperature optima for activity
      of 5.0 and 35 degrees C, respectively. It was heat stable with a D55 of 41 min
      and a D62.5 of 18 h. Molecular weight of the enzyme was estimated to be 52 kDa by
      SDS PAGE and size exclusion chromatography. Values for kM of 144.28, 18.73,
      110.20 and 35.23 micromol were obtained for whole, alpha-, beta- and kappa
      casein, with a Vmax of 8.26, 0.09, 0.42 and 0.70 micromol mg-1 min-1,
      respectively. The enzyme hydrolysed kappa-casein preferentially when incubated
      with artificial casein micelles.

PMID- 10971761
TI  - Outer membrane protein shifts in biocide-resistant Pseudomonas aeruginosa PAO1.
AB  - Benzisothiazolone (BIT), N-methylisothiazolone (MIT) and 5-chloro-N
      methylisothiazolone (CMIT) are highly effective biocidal agents and are used as
      preservatives in a variety of cosmetic preparations. The isothiazolones have
      proven efficacy against many fungal and bacterial species including Pseudomonas
      aeruginosa. However, some species are beginning to exhibit resistance towards
      this group of compounds after extended exposure. This experiment induced
      resistance in cultures of Ps. aeruginosa exposed to incrementally increasing sub
      minimum inhibitory concentrations (MICs) of the isothiazolones in their pure
      chemical forms. The induced resistance was observed as a gradual increase in MIC
      with each new passage. The MICs for all three test isothiazolones and a thiol
      interactive control compound (thiomersal) increased by approximately twofold
      during the course of the experiment. The onset of resistance was also observed by
      reference to the altered presence of an outer membrane protein, designated the T
      OMP, in SDS-PAGE preparations. T-OMP was observed to disappear from the biocide
      exposed preparations and reappear when the resistance-induced cultures were
      passaged in the absence of biocide. This reappearance of T-OMP was not
      accompanied by a complete reversal of induced resistance, but by a small decrease
      in MIC. The induction of resistance towards one biocide resulted in the
      development of cross-resistance towards other members of the group and the
      control, thiomersal. It has been suggested that the disappearance of T-OMP from
      these preparations is associated with the onset of resistance to the
      isothiazolones in their Kathon form (CMIT and MIT).

PMID- 10971762
TI  - Combined action of S-carvone and mild heat treatment on Listeria monocytogenes
      Scott A.
AB  - The combined action of the plant-derived volatile, S-carvone, and mild heat
      treatment on the food-borne pathogen, Listeria monocytogenes, was evaluated. The
      viability of exponential phase cultures grown at 8 degrees C could be reduced by
      1.3 log units after exposure to S-carvone (5 mmol l-1) for 30 min at 45 degrees
      C, while individual treatment with S-carvone or exposure to 45 degrees C for 30
      min did not result in a loss in viability. Other plant-derived volatiles, namely
      carvacrol, cinnamaldehyde, thymol and decanal, were also found to reduce the
      viability of L. monocytogenes in combination with the same mild heat treatment at
      concentrations of 1.75 mmol l-1, 2.5 mmol l-1, 1.5 mmol l-1 and 2 mmol l-1,
      respectively. These findings show that essential oil compounds can play an
      important role in minimally processed foods, and can be used in the concept of
      Hurdle Technology to reduce the intensity of heat treatment or other individual
      hurdles.

PMID- 10971763
TI  - Influence of TNT transformation on microbial community structure in four
      different lake microcosms.
AB  - After World War II, large amounts of obsolete ammunition were dumped in various
      lakes in Sweden. Trinitrotoluene, TNT, was one of the main components of the
      dumped explosives. In this study, four different lake microcosms originating from
      lakes where relatively large amounts of ammunition were dumped were used to mimic
      the effect of TNT release on the natural microbial community. Increased microbial
      growth was found in lake microcosms amended with TNT. However, negligible
      mineralization of TNT was detected, suggesting that TNT was not utilized as a
      carbon source, but as a nitrogen source. Random amplified polymorphic DNA (RAPD)
      analysis indicated that the TNT induced no significant differences in microbial
      community composition and therefore, no major changes in natural selection,
      despite the increased microbial growth in the presence of the compound. More than
      95% of the added TNT bound irreversibly to the sediments, possibly as a result of
      microbial transformation to reactive metabolites that subsequently bound
      covalently to components of the sediment. The results, taken together, suggest
      that no permanent change in the microbial ecology occurred as a result of the TNT
      amendment. This was probably due partly to the transient exposure of the
      microbial communities to the TNT before it became irreversibly bound to the
      sediment, and partly to the fact that TNT was not a primary growth substrate that
      strongly affects natural selection.

PMID- 10971764
TI  - Molecular and insecticidal characterization of a Bacillus thuringiensis strain
      isolated during a natural epizootic.
AB  - A new Bacillus thuringiensis strain belonging to the serovar aizawai was isolated
      from a dead larva of the lepidopteran Mythimna loreyi collected in a corn crop in
      Spain during a natural epizootic. This strain, which was named Leapi01, was
      compared with the kurstaki and aizawai strains isolated from Dipel(R) and
      Xentari(R), by electron microscopy, SDS-PAGE, plasmid pattern, PCR and
      insecticidal activity. This strain showed similar morphological and biochemical
      characteristics to the standard strains. The content in cry genes of Leapi01 was
      analysed with a set of general and specific primers recognizing most of the cry
      genes reported to date. DNA amplification was obtained with primers corresponding
      to six genes and, to clearly determine the identity of the genes, the amplified
      fragments were sequenced and corresponded to cry1Aa, cry1Ab, cry1Ca, cry1Da,
      cry2Ab and cry1Ia. However, the proteins encoded by two of these genes, Cry2 and
      Cry1I, were not detected in the SDS-PAGE of the purified parasporal bodies. The
      insecticidal activity of Leapi01 was determined by bioassays against two
      Lepidoptera species, Helicoverpa armigera and Spodoptera littoralis, that were
      found to be very susceptible to Leapi01 purified crystals. Since two of the cry
      genes identified in Leapi01 appear to be silent, other factors may be involved in
      the toxicity of the strain. As a result of this study, the potential of Leapi01
      as biological control agent is discussed, with special emphasis on the high
      toxicity and relatively broad spectrum activity compared with two B.
      thuringiensis strains that are the active ingredients of commercial preparations
      commonly used as bioinsecticides.

PMID- 10971765
TI  - Lactic acid bacteria associated with the digestive tract of Atlantic salmon
      (Salmo salar L.).
AB  - The present study reports the effect of excessive handling stress and starvation
      on the lactic acid bacteria associated with the digestive tract of Atlantic
      salmon (Salmo salar L.). A relatively low population level (approximately 2 x 103
      bacteria per gram wet tissue) of viable adherent heterotrophic bacteria was
      associated with the digestive tract (foregut, midgut and hindgut). Of the 752
      bacterial isolates isolated from diet, water and the digestive tract, 201
      isolates belonged to the carnobacteria. Of these isolates, one from the diet, one
      from the rearing water and 80 from the gastrointestinal tract, were further
      identified on the basis of 16S rDNA sequence analysis. All these isolates were
      identified as being Carnobacterium piscicola-like. Daily repeated stress and
      starvation of the fish over 11 d had no influence on the total culturable
      bacterial numbers or population level of C. piscicola associated with the
      digestive tract. C. piscicola-like isolates colonizing the various intestinal
      regions (foregut, midgut and hindgut) were also screened for their ability to
      produce growth inhibitory compounds active against the fish pathogen Aeromonas
      salmonicida. Of the 199 C. piscicola isolates tested, 139 inhibited growth of the
      pathogen.

PMID- 10971766
TI  - Variation of microcystin content of microcystis aeruginosa relative to medium N:P
      ratio and growth stage.
AB  - Changes in the microcystin content of Microcystis aeruginosa UTEX 2388 were
      investigated at several N:P ratios of the medium and various growth stages. Under
      the P-fixed condition, the microcystin content of the cells changed with
      different medium N:P ratios, with the highest at 2748 microg g-1 at a N:P ratio
      of 16 after incubation for 7 d. The microcystin content of M. aeruginosa
      exhibited a high correlation with the total N content regardless of an N-fixed or
      P-fixed culture. When the N:P ratio of the medium was fixed to 16 : 1, the
      microcystin content of M. aeruginosa at various growth stages was highest at 2191
      microg g-1 after an incubation of 4 d and the chlorophyll-a content showed a
      similar tendency. There was a highly significant relationship between the
      microcystin content of M. aeruginosa and the chlorophyll-a concentration in the
      culture during the incubation. Accordingly, the microcystin content of M.
      aeruginosa during incubation can be easily estimated and monitored by measuring
      the in vivo fluorescence changes in the culture.

PMID- 10971767
TI  - Mechanisms of killing of spores of Bacillus subtilis by iodine, glutaraldehyde
      and nitrous acid.
AB  - Treatment of wild-type spores of Bacillus subtilis with glutaraldehyde or an
      iodine-based disinfectant (Betadine) did not cause detectable mutagenesis, and
      spores (termed alpha-beta-) lacking the major DNA-protective alpha/beta-type,
      small, acid-soluble proteins (SASP) exhibited similar sensitivity to these
      agents. A recA mutation did not sensitize wild-type or alpha-beta- spores to
      Betadine or glutaraldehyde, nor did spore treatment with these agents result in
      significant expression of a recA-lacZ fusion when the treated spores germinated.
      Spore glutaraldehyde sensitivity was increased dramatically by removal of much
      spore coat protein, but this treatment had no effect on Betadine sensitivity. In
      contrast, nitrous acid treatment of wild-type and alpha-beta- spores caused
      significant mutagenesis, with alpha-beta- spores being much more sensitive to
      this agent. A recA mutation further sensitized both wild-type and alpha-beta-
      spores to nitrous acid, and there was significant expression of a recA-lacZ
      fusion when nitrous acid-treated spores germinated. These results indicate that:
      (a) nitrous acid kills B. subtilis spores at least in part by DNA damage, and
      alpha/beta-type SASP protect against this DNA damage; (b) killing of spores by
      glutaraldehyde or Betadine is not due to DNA damage; and (c) the spore coat
      protects spores against killing by glutaraldehyde but not Betadine. Further
      analysis also demonstrated that spores treated with nitrous acid still germinated
      normally, while those treated with glutaraldehyde or Betadine did not.

PMID- 10971768
TI  - Distribution of alkB genes within n-alkane-degrading bacteria.
AB  - Fifty-four bacterial strains belonging to 37 species were tested for their
      ability to assimilate short chain and/or medium chain liquid n-alkanes. A gene
      probe derived from the alkB gene of Pseudomonas oleovorans ATCC 29347 was
      utilized in hybridization experiments. Results of Southern hybridization of PCR
      amplificates were compared with those of colony hybridization and dot blot
      hybridization. Strongest signals were received only from Gram-negative bacteria
      growing solely with short n-alkanes (C10). Hybridization results with soil
      isolates growing with n-alkanes of different chain lengths suggested as well that
      alkB genes seem to be widespread only in solely short-chain n-alkane-degrading
      pseudomonads. PCR products of Rhodococcus sp., Nocardioides sp., Gordona sp. and
      Sphingomonas sp. growing additionally or solely with medium-chain n-alkane as
      hexadecane had only few sequence identity with alkB though hybridizing with the
      gene probe. The derived amino acid sequence of the alkB-amplificate of
      Pseudomonas aureofaciens showed high homology (95%) with AlkB from Ps.
      oleovorans. alkB gene disruptants were not able to grow with decane.

PMID- 10971769
TI  - The fate of stormwater-associated bacteria in constructed wetland and water
      pollution control pond systems.
AB  - The performances of a constructed wetland and a water pollution control pond were
      compared in terms of their abilities to reduce stormwater bacterial loads to
      recreational waters. Concentrations of thermotolerant coliforms, enterococci and
      heterotrophic bacteria were determined in inflow and outflow samples collected
      from each system over a 6-month period. Bacterial removal was significantly less
      effective in the water pollution control pond than in the constructed wetland.
      This was attributed to the inability of the pond system to retain the fine clay
      particles (< 2 microm) to which the bacteria were predominantly adsorbed.
      Sediment microcosm survival studies showed that the persistence of thermotolerant
      coliforms was greater in the pond sediments than in the wetland sediments, and
      that predation was a major factor influencing bacterial survival. The key to
      greater bacterial longevity in the pond sediments appeared to be the adsorption
      of bacteria to fine particles, which protected them from predators. These
      observations may significantly affect the choice of treatment system for
      effective stormwater management.

PMID- 10971770
TI  - Characterization and mechanism of action of cerein 7, a bacteriocin produced by
      Bacillus cereus Bc7.
AB  - Cerein 7 is a peptidic antibiotic produced by Bacillus cereus Bc7 (CECT 5148) at
      the end of exponential growth but before sporulation onset. Cerein 7 has a broad
      spectrum of antibacterial activity against Gram-positive bacteria, but it is
      inactive against Gram-negative bacteria. The sequence of its amino-terminal end
      and its characteristics of hydrophobicity and molecular mass make cerein 7 unique
      among the bacteriocins produced by the soil bacterium B. cereus. In this paper a
      further characterization of cerein 7 is presented, it is shown that it can be
      classified as a Klaenhammer's class II bacteriocin and that its mode of action
      corresponds to that of a membrane-active compound.

PMID- 10971771
TI  - Evaluation of ChemChrome V6 for bacterial viability assessment in waters.
AB  - The efficiency of ChemChrome B (CB) and ChemChrome V6 (CV6) dyes to stain viable
      bacterial cells in water was compared. Both dyes are fluorogenic esters converted
      to free fluorescein by esterase activity. The dyes were applied to a wide variety
      of bacterial species, including those poorly stained by CB, and to natural
      waters. Some species tested gave unacceptable low fluorescence intensities by
      being inefficiently or non-labelled with the CB. In contrast, CV6-stained
      bacteria were easily detected by both flow cytometry and solid-phase cytometry.
      As a consequence, higher viable cell counts were found with CV6 compared with CB
      in natural waters. Viable counts determined by CV6 staining were always higher
      than cfu counts. In contrast, respiring cell counts (CTC) were always lower than
      CV6 counts and, in the case of tap and mineral waters, they were lower than cfu
      counts.

PMID- 10971773
TI  - Risk of hormone replacement therapy in stroke patients.
AB  - Hormone replacement therapy (HRT) (oestrogen with or without progestin) is often
      initiated with the onset of menopause to decrease symptoms of oestrogen
      deficiency, such as vasomotor instability (hot flashes) and urogenital effects (1
      3). HRT can also prevent long-term consequences of oestrogen deficiency, such as
      osteoporosis and cardiovascular disease (1-3). The decision to start HRT in peri-
      and postmenopausal women is complicated by concerns of increased risk for
      thromboembolic events, uterine cancer and breast cancer (2-4). Thromboembolic
      stroke is a particular concern due to its association with the use of oral
      contraceptives with high oestrogen content (3, 4). However, for older women it
      has been suggested that HRT use decreases or has no effect on stroke risk (5-9).
      Should these findings apply to a women with a history of thromboembolism, in this
      case ischemic stroke?

PMID- 10971772
TI  - Inhaled corticosteroids and chronic obstructive pulmonary disease.

PMID- 10971774
TI  - The impact of information technology on the performance of clinical pharmacy
      services.
AB  - Electronic patient records are now being developed to assist in the clinical
      management of patients within secondary care. This paper reviews how various
      types of information technology used in these electronic patient records can
      improve the performance of clinical pharmacy services. The different levels of
      information technology support for some of the main aspects of clinical pharmacy
      services are described. How the impact and outcome of information technology
      support for these services should be evaluated are discussed. The human and
      technological factors that must be considered to ensure that the implementation
      succeeds and the potential benefits are realized are examined.

PMID- 10971775
TI  - Management of urinary incontinence.
AB  - Urinary incontinence is one of the most embarrassing disabilities in the elderly
      people. It may be defined as an involuntary loss of urine in a quantity or
      frequency sufficient to cause a social or hygienic problem. Its magnitude is both
      overlooked and underestimated by the medical community. Unfortunately, urinary
      incontinence lacks the glamour of other 'high tech' medical problems.

PMID- 10971776
TI  - 2-hydroxypropyl-beta-cyclodextrin increases aqueous solubility and photostability
      of all-trans-retinoic acid.
AB  - BACKGROUND: All-trans-retinoic acid (ATRA, vitamin A acid or tretinoin) is
      effective in the treatment of acute promyelocytic leukaemia (APL). Unfortunately,
      the oral absorption of ATRA is highly variable. Its poor aqueous solubility also
      makes it difficult to be formulated into parenteral formulation. To date, there
      is no parenteral formulation of ATRA available commercially. OBJECTIVE: To
      undertake the preformulation work necessary for developing such a product.
      METHOD: We investigated the solubility and stability profile of ATRA in various
      formulations. RESULTS: The aqueous solubility of ATRA could be greatly increased
      by the inclusion of ATRA in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD).
      Adjusting the pH value further improved the water solubility of ATRA. The
      photostability of HP-beta-CD-based formulation of ATRA was evaluated and it was
      found that inclusion ATRA into HP-beta-CD did improve the photostability of ATRA.
      CONCLUSION: These results showed that it is possible to develop a parenteral
      formulation and/or an aqueous oral formulation of all-trans-retinoic acid by
      using 2-hydroxypropyl-beta-cyclodextrin. However, the biopharmaceutical
      properties of such a formulation would be necessary before its use.

PMID- 10971777
TI  - Long-term effects of nitrous oxide anaesthesia on laboratory and clinical
      parameters in elderly Omani patients: a randomized double-blind study.
AB  - AIMS: This study examined the long-term effects of nitrous oxide anaesthesia on
      serum levels of cobalamin and folate, red cell folate levels and haematological
      parameters, and neurological status in elderly Omani patients. METHODS: Sixty
      nine consecutive patients undergoing ophthalmic surgery were randomly and double
      blind assigned to nitrous oxide or propofol anaesthesia. They met the following
      entry criteria: age 55 years or above, no major organ failure, no clinical signs
      or symptoms of cobalamin or folate deficiency, mean cell volume (MCV) </= 96 fl,
      haematocrit (Hct) higher than 0.3 and no cobalamin and/or folate substitution
      therapy during the preceding months. Serum levels of cobalamin and folate, red
      cell folate levels, and haematological parameters were measured prior to
      anaesthesia and 3-5 weeks later. At that time, the patients also underwent
      thorough neurological examination. RESULTS: Data of 51 patients were complete and
      considered for analysis. In both nitrous oxide and propofol group, the range of
      exposure time was comparable (+/-1 h). In the nitrous oxide group, a slight but
      significant decrease in haemoglobin, Hct, and red blood cell count (RBC) (P <
      0.001) was observed, whereas there was a mild increase in mean cell haemoglobin
      (MCH) and mean cell volume (P < 0.05). In addition, there was a significant
      decrease in serum folate levels (P < 0.05). Hct and RBC decreased slightly in the
      propofol group (P < 0. 05), whereas there was a small increase in MCH. There was
      no difference between the two anaesthetics with regard to serum cobalamin and red
      cell folate levels, but there was a significant decrease in serum folate levels
      in the nitrous oxide group compared to those in the propofol group. Three
      patients with pre-existing low red cell folate levels, who were randomized to
      nitrous oxide anaesthesia, developed clinical symptoms of folate deficiency.
      CONCLUSION: This study showed that short-term (40-80 min) nitrous oxide
      anaesthesia did not affect cobalamin levels but reduced serum folate levels in
      this elderly population. Although this reduction was clinically irrelevant, some
      patients with pre-existing asymptomatic folate deficiency developed nitrous oxide
      induced folate deficiency.

PMID- 10971778
TI  - Potential interaction between troglitazone and atorvastatin.
AB  - BACKGROUND: Troglitazone is a CYP3A4 isoenzyme inducer known to decrease the
      plasma concentration of drugs metabolized by CYP3A4. Atorvastatin, a known
      substrate of the CYP3A4 pathway, is often used in combination with troglitazone
      for diabetic patients with dyslipidemia. AIMS: The purpose of this study was to
      investigate the clinical effects of troglitazone on the fasting lipid profiles of
      patients receiving atorvastatin. METHOD: We retrospectively reviewed the medical
      records of patients who received concomitant troglitazone and atorvastatin
      therapy during a 24-month period. Patients were included in the analysis if
      during the study period, complete laboratory data were available (fasting lipid
      profile and glycosylated haemoglobin), the dose of atorvastatin remained
      unchanged, there were no changes in the diabetic drug regimen, patients received
      at least 3 months of combination therapy and patients were adherent with their
      medication. RESULTS: Four out of 31 (13%) patients satisfied the inclusion
      criteria. All of these patients were male, with a mean age of 63. All patients
      were receiving insulin only for diabetes control when the troglitazone was added.
      There was an increase in LDL-cholesterol and triglycerides of 23.3% and 21.3%,
      respectively. CONCLUSION: The increase in LDL-cholesterol and triglycerides on
      atorvastatin and troglitazone combination therapy compared with atorvastatin mono
      therapy is suggestive of a drug interaction. Further studies involving
      troglitazone and atorvastatin may be warranted to substantiate this interaction.

PMID- 10971779
TI  - Endotoxin testing of proteins for parenteral administration using the Mono Mac 6
      assay.
AB  - BACKGROUND: Pharmaceutical products containing proteins cause problems in testing
      for endotoxin and pyrogens. Many proteins interfere with the LAL test and the
      proteins are immunogenic in rabbits. The monocytic cell line Mono Mac 6 is an
      alternative assay for detection of endotoxin and other pyrogens. OBJECTIVE: To
      evaluate the use of the Mono Mac 6 assay for quantitative detection of endotoxin
      in proteins. METHOD: The quantitative detection of endotoxin in the three
      pharmaceutical products human albumin, gamma-globulin and somatropin was
      evaluated. RESULTS: For the three proteins the detection limit of the Mono Mac 6
      assay was far below the threshold endotoxin limit described by the European
      Pharmacopoeia. Interference of two of the proteins with the Mono Mac 6 assay was
      observed, but the problems could be overcome either by dilution of the product or
      by comparison of the test with an endotoxin standard curve prepared in a solution
      of the respective pyrogen-free protein. CONCLUSION: The Mono Mac 6 assay is a
      reliable method for quantitative detection of endotoxin in proteins.

PMID- 10971780
TI  - Plasma transforming growth factor beta1 in breast cancer patients treated with
      CMF chemotherapy.
AB  - BACKGROUND: In early breast cancer patients the transformed epithelial cells are
      thought to be sensitive to transforming growth factor beta1 (TGFbeta1)-mediated
      growth arrest. TGFbeta1 may therefore act as an anti-tumour promoter. However, in
      advanced breast cancer resistance to such TGFbeta1 action develops. Neoplastic
      cells produce TGFbeta1, which may enhance tumour invasion and metastasis, mainly
      by intensifying angiogenesis, which is an immunosuppressive action. In the light
      of the potential role of TGFbeta1 in breast cancer pathogenesis, an understanding
      of the effect of applied therapeutic methods on plasma TGFbeta1 concentration is
      essential. OBJECTIVE: To investigate the effect of adjuvant chemotherapy on
      plasma transforming growth factor beta1 (TGFbeta1) concentration in breast cancer
      patients with metastases to axillary lymph nodes. METHOD: Fifteen stage II breast
      cancer patients on adjuvant chemotherapy with cyclophosphamide, methotrexate and
      5-fluorouracil (CMF) were studied along with 15 healthy premenopausal women.
      RESULTS: Plasma TGFbeta1 concentration (determined by the ELISA method) in the
      breast cancer patients did not differ significantly from that of the healthy
      women. Adjuvant CMF chemotherapy significantly decreased plasma TGFbeta1
      concentration in those pre-menopausal breast cancer women with metastases to
      axillary lymph nodes. CONCLUSION: The possible pathogenic action of this growth
      factor in stage II breast cancer disease warrants further investigation to
      elucidate whether the induced decrease of blood TGFbeta1 concentration is
      essential to successful chemotherapy.

PMID- 10971781
TI  - Leflunomide and rheumatoid arthritis: a systematic review of effectiveness,
      safety and cost implications.
AB  - OBJECTIVE: To assess the effectiveness, safety and cost implications of
      leflunomide treatment for rheumatoid arthritis. DESIGN: Systematic review.
      SETTING: Four trials retrieved from Medline, Embase, the Cochrane Library,
      Econlit, HMIC (Dhdata), HMIC (Helmis), HMIC (King's Fund Database) and Best
      Evidence3. MAIN OUTCOME MEASURES: Efficacy measures (including tender joint
      counts, swollen joint counts, assessment of functioning, Health Assessment
      Questionnaire, Modified Health Assessment Questionnaire, pain (visual analogue
      scale), Erythrocyte Sedimentation Rate, C-reactive Protein), radiological
      progression and treatment adverse events. RESULTS: Leflunomide therapy was
      demonstrated to be significantly superior to placebo in relation to the efficacy
      outcome measures and it slowed the radiological progression of patients' disease
      in three studies. Treatment success and duration of sustained response were also
      significantly superior than on placebo, as were quality of life measures.
      Leflunomide treatment was comparable to sulphasalazine and methotrexate with
      respect to efficacy, radiological progression and quality of life measures. The
      most common adverse effects leading to withdrawal from leflunomide treatment were
      gastrointestinal symptoms (diarrhoea and nausea), allergic reactions (rash and
      pruritus), alopecia, dyspepsia, hypertension and elevated transaminase levels.
      Weight loss and dizziness have also been reported for leflunomide therapy.
      Leflunomide is more expensive than most DMARDs, costing about pound400 a year
      more than sulphasalazine. CONCLUSION: Despite the small number of published
      articles relating to leflunomide treatment, the evidence suggests that
      leflunomide is similar in efficacy to both sulphasalazine and methotrexate,
      although with a differential pattern of side-effects. There is a need for further
      research to assess the long-term outcomes of leflunomide treatment.

PMID- 10971782
TI  - Aminoglycoside usage and monitoring in a Saudi Arabian teaching hospital: a ten
      year laboratory audit.
AB  - BACKGROUND AND OBJECTIVE: In 1989, a therapeutic drug monitoring service was
      established in Assir Central Hospital, Abha, Saudi Arabia, by the Department of
      Clinical Pharmacology and Therapeutics of the College of Medicine, King Saud
      University Abha Branch (now King Khalid University). We report a 10-year follow
      up of the results of monitoring the commonly used aminoglycosides (amikacin,
      gentamycin and tobramycin) obtained from our adult patients on first monitoring.
      METHOD: Two educational seminars for doctors and nurses were conducted 6 months
      before the initiation of this study. Drug assay requests were made on specially
      designed forms. Drug dosages were determined by the attending physicians. Samples
      for peak and trough drug level determinations were drawn after the fourth dose.
      The results of first time monitoring were sent to the wards with appropriate
      comments for dosage modifications where indicated. RESULTS: The results for 2022
      patients were analysed. Of these, 929, 899 and 194 were for amikacin, gentamycin
      and tobramycin, respectively. Therapeutic trough concentrations were 71.2%, 28.3%
      and 28.3% of patients on amikacin, gentamycin and tobramycin, respectively. A
      total of 8.8%, 17.6% and 11.9% had trough concentrations considered toxic for
      amikacin, gentamycin and tobramycin, respectively. Peak therapeutic
      concentrations were achieved in 31.6%, 42.3% and 39.7% of patients on amikacin,
      gentamycin and tobramycin. A total of 53.3% of patients on amikacin, 50.3% on
      gentamycin and 57.2% on tobramycin had peak serum drug concentrations in the
      subtherapeutic range. Toxic concentrations were noticed mainly in patients aged
      over 60 years and in the critically ill in the intensive care, coronary care and
      bums units of the hospital. CONCLUSION: To be cost-effective, intensive
      therapeutic monitoring of aminoglycosides in adults should continue to be
      monitored mainly for the old and sick patients in critical care units to optimize
      patient management.

PMID- 10971783
TI  - Managed substitution of modified release nitrates with an asymmetric dosing
      regimen.
AB  - BACKGROUND: Orally administered modified release organic nitrates are used
      commonly in the prophylaxis of myocardial ischaemia, although little evidence
      indicates a clinically superior response compared with standard formulated
      preparations administered symmetrically. AIM: To investigate the clinical success
      of transfer of suitable patients from MR to SF nitrates. METHOD: Suitable
      candidates for therapeutic substitution, assessed by a pharmacist, completed a
      baseline study to estimate frequency and timing of chest pain, the number of
      rescue doses of sublingual nitrates required, together with an assessment of
      adverse effects experienced. Following substitution to an eccentric dosing
      schedule, a further one month's assessment of chest pain frequency, rescue
      nitrate use and adverse effects was recorded and compared with baseline. RESULTS:
      Twelve (37.5%) patients from a possible 32 candidates were invited to complete a
      baseline symptoms and adverse event diary. Eight patients entered the study phase
      (66.7% of the 12 included in the baseline phase of the study). These candidates
      showed no evidence of loss of control of chest pain symptoms, 3.5 +/- 1.16 (mean
      +/- standard error of mean) episodes/patient/28 days compared with 1.9 +/- 0.96
      episodes/patient/28 days during the test phase (P > 0.05). Similarly, there was
      no difference in the number of doses of rescue nitrates required when the trial
      phase (2.6 +/- 1.63 doses/patient/28 days) was compared with the control (2.0 +/-
      1.31 doses/patient/28 days, P > 0.05). There was no evidence of an increased
      incidence of adverse effects during the trial period of the study. CONCLUSION:
      This small study suggests that, if selected carefully, therapeutic substitution
      of MR oral nitrates can be managed successfully without apparent risk of loss of
      symptom control or increased incidence of adverse effects.

PMID- 10971784
TI  - Infections as a major preventable cause of human cancer.
AB  - Infections may be responsible for over 15% of all malignancies worldwide.
      Important mechanisms by which infectious agents may induce carcinogenesis include
      the production of chronic inflammation, the transformation of cells by insertion
      of oncogenes and inhibition of tumour suppressors, and the induction of
      immunosuppression. Common characteristics shared by infectious agents linked to
      malignancies are that they are persistent in the host, often highly prevalent in
      the host population and induce cancer after a long latency. The associations
      between a selection of infectious agents and malignancies are covered in detail.

PMID- 10971785
TI  - Progress in haematopoietic stem cell transplantation for multiple myeloma.
AB  - High-dose myeloablative treatment followed by autologous haematopoietic stem cell
      transplantation has significantly improved survival of patients younger than 65
      years of age with multiple myeloma as compared with conventional chemotherapy.
      However, all patients seem to relapse and molecular remissions are rare. Results
      of allogeneic transplantation, still hampered by high transplant-related
      mortality, have improved dramatically over the last 5-6 years and this is an
      option for patients younger than 50-55 years old. The relapse rate is lower than
      with autologous transplantation and molecular remissions are frequent. Some
      patients are still in complete haematological remission more the 10 years
      following transplantation. Autologous transplantation followed by
      nonmyeloablative allogeneic transplantation is on trial and may be a way to
      eventually cure a fraction of younger patients with multiple myeloma.

PMID- 10971786
TI  - Risk factor clustering in hypertensive patients: impact of the reports of NCEP-II
      and second joint task force on coronary prevention on JNC-VI guidelines.
AB  - INTRODUCTION: Although the association of hypertension with established risk
      factors has been noted in several population studies, the recent redefinition of
      dyslipidaemia, hypertension and diabetes calls for reassessment of the prevalence
      and pattern of risk factor clusters in essential hypertension. OBJECTIVE: To
      analyse the risk factor profile of Israeli patients with essential hypertension
      seen by primary care physicians and in hypertension specialty clinics, based on
      current definitions of dyslipidaemia hypertension and diabetes and JNC-VI
      guidelines for the assessment of risk factors. DESIGN AND SETTING: We analysed
      the risk profile of 324 Israeli hypertensive subjects using the JNC-VI risk table
      and risk grouping. A total of 122 consecutive patients were recruited from
      primary care clinics and 212 consecutive patients were recruited from a hospital
      based hypertension clinic. RESULTS: Amongst hypertensive individuals with no
      known target organ damage, only 1.5% had no risk factors other than hypertension,
      whereas all hypertensives with coronary artery disease had additional risk
      factors. Of the six listed major JNC-VI risk factors (smoking, dyslipidaemia,
      diabetes, age, sex, family history of cardiovascular disease), hypertensive
      subjects without coronary artery disease (coronary artery disease-negative) had
      3.02 +/- 0.10 risk factors, whereas hypertensive subjects with coronary artery
      disease (coronary artery disease positive) had 3.6 +/- 0.07 risk factors other
      than hypertension (P < 0.01). Dyslipidaemia defined by NCEP-II criteria was the
      most common associated risk factor identified in 93% of coronary artery disease
      positive and 77% of the coronary artery disease-negative hypertensive subjects.
      The most common dyslipidaemic abnormality was an increased LDL cholesterol (79.2%
      of the cohort), followed by hypertriglyceridaemia (31.7%) and low HDL cholesterol
      (22.3%). Nevertheless, in nearly half of the coronary artery disease-negative
      patients, LDL cholesterol concentrations were within 30 mg dL-1 of the target
      levels. The most common dyslipidaemic variant was isolated hypercholesterolaemia
      (42%), whereas the syndrome X dyslipidaemic combination of hypertriglyceridaemia
      and low HDL was strikingly uncommon, observed in 2.8% of the coronary artery
      disease-positive and 0.8% of the coronary artery disease-negative patients.
      CONCLUSIONS: (i) JNC-VI group risk A patients (no risk factors) comprise a very
      small minority in this cohort (< 5%); (ii) dyslipidaemia is exceedingly common
      with mild hypercholesterolaemia being the most prevalent variant and
      hypertriglyceridaemia with low HDL the least common form.

PMID- 10971787
TI  - Consumption of French-press coffee raises cholesteryl ester transfer protein
      activity levels before LDL cholesterol in normolipidaemic subjects.
AB  - OBJECTIVES: To determine the long-term effects of unfiltered coffee consumption
      on the activity levels of cholesteryl ester transfer protein (CETP), phospholipid
      transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) and to
      assess a possible role of CETP activity levels in the rise in serum LDL
      cholesterol. SUBJECTS AND DESIGN: Forty-six healthy normolipidaemic subjects
      consumed 0.9 L of either French-press or filtered coffee for 24 weeks. Fasting
      blood samples were obtained after 0, 2, 12 and 24 weeks of intervention and after
      and 12 weeks of follow-up. MAIN OUTCOME MEASURES: Serum activity levels of CETP,
      PLTP and LCAT. RESULTS: Relative to baseline, French-press coffee significantly
      increased average CETP activity by 12% after 2 weeks, by 18% after 12 weeks, and
      by 9% after 24 weeks. PLTP activity was significantly increased by 10% after 12
      and 24 weeks. LCAT activity was significantly decreased by 6% after 12 weeks and
      by 7% after 24 weeks. The increase in CETP clearly preceded the increase in LDL
      cholesterol, but not the increase in total triglycerides. However, consumption of
      French-press coffee caused a persistent rise in CETP activity, whereas the rise
      in serum triglycerides was transient. CONCLUSIONS: Consumption of cafestol and
      kahweol cause a long-term increase in CETP as well as PLTP activity; the increase
      in CETP activity may contribute to the rise in LDL cholesterol.

PMID- 10971788
TI  - Plasma total homocysteine concentration and the risk of acute coronary events:
      the Kuopio Ischaemic Heart Disease Risk Factor Study.
AB  - OBJECTIVES: Results from prospective studies concerning the association between
      plasma total homocysteine (tHcy) concentration and coronary heart disease (CHD)
      are conflicting. The purpose of this study was to test the hypothesis that plasma
      tHcy is associated with an increased risk of acute coronary events in middle-aged
      men. DESIGN AND SUBJECTS: We investigated this association in a prospective
      nested case-control study among Eastern Finnish men aged 42-60 years. Plasma tHcy
      measurements were carried out for 163 men who had an acute coronary event during
      an average 8 years and 11 months follow-up of the whole cohort and for 163
      control subjects. Both the cases and the controls were from a cohort of 2005 men
      who had no clinical CHD at the Kuopio Ischaemic Heart Disease (KIHD) baseline.
      RESULTS: Men in the highest plasma tHcy concentration quarter had no increase in
      the risk of coronary events compared with men with lower tHcy concentrations
      (odds ratio = 0.88, 95% confidence interval 0.44-1.76). Average follow-up time
      before the first coronary event was 4.9 years (SD 3.2) in men in the highest
      plasma tHcy quarter and 5.5 years (SD 3.1) in men in the three lowest quarters (P
      = 0.368). CONCLUSION: We conclude that plasma tHcy is not associated with an
      increased risk of coronary events in the middle-aged male population in eastern
      Finland.

PMID- 10971789
TI  - The effect of different treatment regimens in reducing fasting and postmethionine
      load homocysteine concentrations.
AB  - OBJECTIVES: To determine the homocysteine-lowering effect of different treatment
      regimens on both fasting and postmethionine-load plasma total homocysteine (tHcy)
      concentrations. DESIGN: Descriptive study of consecutive hyperhomocysteinaemic
      subjects per treatment regimen. Homocysteine was measured in the fasting state
      and 6 h after methionine loading, both before and after 8 weeks of vitamin
      therapy. Hyperhomocysteinaemia was defined as a fasting tHcy and/or increase in
      tHcy (postmethionine-load minus fasting tHcy concentration) exceeding the 95th
      percentile of local controls. SETTING: Outpatient clinic of internal medicine of
      a large non-academic teaching hospital. SUBJECTS: One hundred and seventeen
      hyperhomocysteinaemic subjects (vascular patients and first-degree relatives).
      INTERVENTIONS: There were four regimens: pyridoxine, 200 mg; folic acid, 5 mg;
      combination of folic acid 0.5 mg and pyridoxine 100 mg; and folic acid, 0.5 mg
      daily. RESULTS: All regimens, except pyridoxine 200 mg, significantly reduced
      fasting tHcy without differences in the percentage reduction (32-38%). All
      regimens produced a significant reduction in the increase in tHcy and
      postmethionine-load tHcy. The reduction in postmethionine-load tHcy was smaller
      for pyridoxine 200 mg than for combination therapy. No differences were found in
      the percentage reduction (for both increase in tHcy and postmethionine-load tHcy)
      between folic acid 5 mg and folic acid 0.5 mg. CONCLUSIONS: Monotherapy folic
      acid (0.5 mg daily) is the lowest effective therapy for reducing both fasting and
      postmethionine-load tHcy concentrations, with the same results as high-dose folic
      acid (5 mg daily). Pyridoxine has no additional value.

PMID- 10971790
TI  - Gamma-glutamyl transpeptidase and the metabolic syndrome.
AB  - OBJECTIVE: To analyse the associations between serum gamma-glutamyl
      transpeptidase activity (GTP) and the components of the metabolic syndrome.
      DESIGN: Cross-sectional, observational study of hypertensive patients and
      controls. SETTING: The participating subjects visited the research laboratory of
      the Department of Internal Medicine, University of Oulu, Oulu, Finland. SUBJECTS:
      A total of 1045 Caucasians, 40-59 years of age, consisting of 261 drug-treated
      hypertensive men, 258 drug-treated hypertensive women and 526 age- and sex
      matched controls. MAIN OUTCOME MEASURES: The associations between GTP and the
      cardiovascular risk factors were analysed through multiple regression and
      logistic methods and by GTP tertiles. The independent effect of GTP on different
      insulin measures, calculated from the values of 2 h of oral glucose tolerance
      test, was estimated after concurrent adjustment for age, obesity and alcohol
      consumption. RESULTS: GTP correlated highly significantly with the components of
      the metabolic syndrome. The correlation coefficient were 0.33 between GTP and
      body mass index, 0. 25 between GTP and systolic blood pressure in control men (P
      = 0. 0001), 0.39 between GTP and triglycerides, and 0.32 between GTP and fasting
      insulin in hypertensive women (P = 0.0001). The association between GTP and blood
      pressure remained significant only at upright measurements in controls. All
      insulin measures had a significant positive association with increasing GTP
      tertiles in all the study groups (e.g. fasting insulin 8.1 mU L-1 in the lowest
      and 11.0 mU L-1in the highest tertile in control women, P = 0.0001), with the
      exception of fasting insulin in control men. In a pooled logistic analysis after
      adjustment for age, body mass index, alcohol consumption and gender, the
      independent predictors of the metabolic syndrome were body mass index, uric acid,
      total cholesterol and GTP (for log-transformed GTP odds ratio 4.0, 95% CI: 2.80
      5.69). CONCLUSIONS: There are significant associations between GTP and the
      components of the metabolic syndrome. Elevated levels of GTP may not always
      indicate increased alcohol consumption, but may also suggest the existence of the
      metabolic syndrome with its subsequent deleterious consequences.

PMID- 10971791
TI  - Polymorphisms of the beta2-adrenergic receptor gene (ADRB2) in relation to
      cardiovascular risk factors in men.
AB  - OBJECTIVE: To investigate the effect of polymorphisms in codon 16 (Arg16Gly) and
      codon 27 (Gln27Glu) of the beta2-adrenergic receptor gene (ADRB2) on
      anthropometric, endocrine, metabolic and haemodynamic variables. DESIGN: A cross
      sectional study. SUBJECTS: A subgroup of 284 Swedish men from a population sample
      of 1040 at the age of 51 years. MAIN OUTCOME MEASURES: Genotype examination of
      ADRB2 polymorphisms in codon 16 and codon 27 with polymerase chain reaction and
      restriction fragment length polymorphism. Anthropometric measurements included
      body mass index, waist-to-hip ratio and abdominal sagittal diameter. Endocrine
      measurements included blood levels of testosterone, insulin-like growth factor I,
      and leptin plus salivary cortisol. Overnight fasting values of serum insulin,
      blood glucose, triglycerides, total, low and high density lipoprotein
      cholesterol, as well as blood pressure and resting heart rate, were also
      determined. RESULTS: Polymorphisms were frequent in both codon 16 and codon 27.
      The Arg16Gly genotype showed significant relationships to elevated central
      distribution of body fat and to systolic blood pressure, whilst the Glu27Glu
      genotype was associated with elevated leptin and triglyceride levels but not to
      other measurements, including obesity variables. CONCLUSIONS: We conclude that
      only a few cardiovascular risk factors are associated with DNA sequence variation
      in the ADRB2 in Swedish men.

PMID- 10971792
TI  - The effect of orlistat on body weight and coronary heart disease risk profile in
      obese patients: the Swedish Multimorbidity Study.
AB  - OBJECTIVE: To assess the effect of orlistat on body weight and cardiovascular
      risk amongst obese patients at high coronary risk. DESIGN: After screening,
      patients entered a two-week single-blind placebo lead-in period, during which
      they followed a mildly hypocaloric diet, before being randomized to double-blind
      treatment with either orlistat 120 mg or placebo three times daily, in
      conjunction with dietary intervention for 1 years. SETTING: The study was
      conducted at 33 primary care centres in Sweden. SUBJECTS: A total of 382 obese
      adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia
      and/or hypertension were recruited, of whom 376 were randomized to orlistat (n =
      190) or placebo (n = 186). MAIN OUTCOME MEASURES: Change in body weight, waist
      and hip circumferences, blood pressure, serum lipid profile, fasting glucose and
      HbA1c. RESULTS: After 1 years, mean weight loss was significantly greater with
      orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly
      more orlistat-treated patients than placebo recipients maintained weight loss of
      > or = 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with
      significantly greater improvements than placebo in total serum cholesterol (-
      3.3% vs. -0.5%; P < 0.05), LDL-cholesterol (- 7.0% vs. -1.1%; P < 0.05), fasting
      glucose (5.1% vs. -0.1%; P < 0.01) and HbA1c (- 2.7% vs. -0.5%; P < 0.05).
      Similar results were reported for the subgroup of patients with type 2 diabetes.
      Orlistat was well tolerated. CONCLUSIONS: Treatment with orlistat in conjunction
      with diet promotes significantly greater weight loss and cardiovascular risk
      factor reduction than diet alone amongst obese patients at high risk of future
      coronary events.

PMID- 10971793
TI  - Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of
      neurological symptoms in patients with hereditary haemorrhagic telangiectasia
      (HHT).
AB  - BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly
      inherited disease. HHT is characterized by a wide variety of clinical
      manifestations, including pulmonary arteriovenous malformations (PAVMs) and
      neurological symptoms. OBJECTIVE: To estimate (i) the prevalence of PAVM, and
      (ii) the occurrence of neurological symptoms in a geographical well-defined
      population of HHT patients. METHODS: HHT family members were invited to a
      clinical examination including registration of HHT manifestations, screening for
      pulmonary arteriovenous malformations and neurological evaluation. Two groups
      served as controls: (i) first-degree relatives without any signs of HHT; and (ii)
      age- and gender-matched controls. SETTING: Odense University Hospital. SUBJECTS:
      HHT patients identified in a cross-sectional family survey carried out in the
      County of Fyn, Denmark. RESULTS: Included in the study were 169 HHT family
      members representing 24 families. They included both HHT patients and their first
      degree relatives. The criteria of HHT were fulfilled in 75 participants; of
      these, 59 had a screening procedure performed, and PAVMs were demonstrated at
      pulmonary angiography (PA) in 18. Seven of the HHT patients had a history of
      cerebral stroke, compared with none of their healthy first-degree relatives.
      CONCLUSION: The prevalence of PAVM was 24% amongst HHT patients. The study
      confirmed an increased prevalence of neurological symptoms amongst HHT patients;
      the odds ratio was estimated to be 7.6. In order to enable prevention of these
      complications, screening for PAVM should become an integral part of the medical
      care for HHT patients.

PMID- 10971794
TI  - Toxin-mediated haemolytic uraemic syndrome without diarrhoea.
AB  - A 52-year-old previously healthy man was admitted to the hospital with
      haematuria, painful micturition and fever. Laboratory investigation showed the
      presence of a haemolytic uraemic syndrome (HUS), characterized by haemolysis,
      renal insufficiency and mental disturbances. A urinary tract infection caused by
      a verotoxin-producing E. coli other than O157:H7 was diagnosed. Treatment of this
      infection resulted in his complete recovery from the illness. Both the search for
      a focus outside the gastrointestinal tract and the search for verotoxin genes by
      specific polymerase chain reaction can be crucial in a patient with HUS without
      preceding diarrhoea.

PMID- 10971795
TI  - Hyperhomocysteinaemia and activated protein C resistance in Behcet's disease.

PMID- 10971796
TI  - Increased plasma vascular endothelial growth factor levels in patients with
      angiodysplasia.

PMID- 10971797
TI  - Applications of gold cluster compounds in immunocytochemistry and correlative
      microscopy: comparison with colloidal gold.
AB  - In this review, we discuss the immunocytochemical literature with respect to a
      comparison between conventional colloidal gold and gold cluster compounds as
      immunoprobes. The relative advantages and disadvantages of each of these types of
      particle for immunocytochemical applications are discussed. We present results
      from our own laboratories and those of others on the comparison of these
      immunoprobes in selected experimental situations. These results show the use of
      gold cluster compounds at both light and electron microscope levels. At the
      ultrastructural level, gold cluster compounds have been used in pre-embedding
      labelling of cultured cells, and for labelling of ultrathin cryosections and
      freeze-fracture preparations. Recently, fluorescently tagged gold cluster
      compounds have become available. Using ultrathin cryosections of human
      neutrophils as a model system, we demonstrate that a single immunoprobe (i.e. a
      fluorescently tagged gold cluster compound) is a robust probe for correlative
      fluorescence and electron microscopy.

PMID- 10971798
TI  - Two new microscopical variants of thermomechanical modulation: scanning thermal
      expansion microscopy and dynamic localized thermomechanical analysis
AB  - We describe two ways in which thermomechanical modulation may be used in
      conjunction with scanning thermal microscopy, in order to distinguish between
      different components of an inhomogeneous sample. The sample is subjected to a
      modulated mechanical stress, and the heating is supplied locally by the probe
      itself. Scanning thermal expansion microscopy is an imaging mode, in which an
      imposed localized temperature modulation is used to generate thermal expansion,
      which in turn produces mechanical strain and gives thermal expansion contrast
      images. We present results using two types of active thermal probe. For
      polymer/resin samples, the depth of material contributing to the measured thermal
      expansion is typically a few micrometres. Under certain conditions we observe a
      reversal in contrast as the frequency of the temperature modulation is increased.
      In dynamic localized thermomechanical analysis, the modulated stress is applied
      directly, and accompanied by a localized temperature change, as used in other
      forms of localized thermal analysis. The resulting modulated lateral force
      signals are obtained. The glass transition of polystyrene is detected, and shows
      a significant variation with frequency. The amplitude or phase signal may be used
      to obtain image contrast for inhomogeneous samples.

PMID- 10971799
TI  - Cathodoluminescence imaging and spectroscopy by near-field detection
AB  - Using near-field techniques, we have developed an experimental set-up for
      spatially resolved cathodoluminescence (CL) spectroscopy and monochromatic
      imaging. It combines a scanning near-field optical/force microscope with a
      scanning electron microscope equipped with a field emission gun. The
      potentialities of this scanning near-field cathodoluminescence microscope are
      demonstrated on two kinds of sample: an indented MgO crystal and AlGaN/GaN
      quantum wells grown on GaN/sapphire. Monochromatic CL imaging allows a clear
      distinction between the emission of quantum wells and the GaN substrate, and for
      the MgO crystal, the localization on the slip bands, near the indentation, of
      luminescent centres emitting at 450 nm.

PMID- 10971800
TI  - Charge effect in point projection images of carbon fibres
AB  - Nanometre-sized carbon fibres across holes have been observed in a lensless point
      projection field-emission microscope operating between 100 and 300 eV. At
      sufficiently high magnification fringe patterns appear; with the help of
      simulations we show that they are strongly dependent on the charge density of the
      fibres. These patterns are characterized by an odd number of fringes with a
      central fringe that becomes very bright as the charge increases. Average diameter
      and linear charge density have been obtained with remarkable precision from
      analysis of fringes. Charge distribution from the middle to the edge of fibres
      has been investigated as well as narrowings at localized places on the fringe
      pattern. From these two examples, the limits of the models used for the
      simulations and those of the data acquisition system are discussed. Finally, this
      work emphasizes the fact that the fringe pattern masks the actual form of the
      fibre and that it is necessary to take account of the charge effect to interpret
      this diffraction pattern.

PMID- 10971801
TI  - X-ray microanalysis of cultured keratinocytes: methodological aspects and effects
      of the irritant sodium lauryl sulphate on elemental composition.
AB  - Irritant substances have been shown to induce elemental changes in human and
      animal epidermal cells in situ. However, skin biopsies are a complicated
      experimental system and artefacts can be introduced by the anaesthesia necessary
      to take the biopsy. We therefore attempted to set up an experimental system for X
      ray microanalysis (XRMA) consisting of cultured human keratinocytes. A number of
      methodological aspects were studied: different cell types, washing methods and
      different culture periods for the keratinocytes. It was also investigated whether
      the keratinocytes responded to exposure to sodium lauryl sulphate (SLS) with
      changes in their elemental composition. The concentrations of biologically
      important elements such as Na, Mg, P and K were different in HaCaT cells (a
      spontaneously immortalized non-tumorigenic cell line derived from adult human
      keratinocytes) compared to natural human epidermal keratinocytes. The washing
      procedure and time of culture influenced the intracellular elemental content, and
      rinsing with distilled water was preferred for further experiments. Changes in
      the elemental content in the HaCaT cells compatible with a pattern of cell injury
      followed by repair by cell proliferation were seen after treatment with 3.33
      microM and 33 microM SLS. We conclude that XRMA is a useful tool for the study of
      functional changes in cultured keratinocytes, even though the preparation methods
      have to be strictly controlled. The method can conceivably be used for predicting
      effects of different chemicals on human skin.

PMID- 10971802
TI  - Temperature-controlled microscopy for imaging living cells: apparatus, thermal
      analysis and temperature dependency of embryonic elongation in Caenorhabditis
      elegans.
AB  - A new experimental apparatus for temperature-controlled microscopy has been
      developed for the study of the temperature dependency of developmental processes
      in the nematode Caenorhabditis elegans. However, the application of this
      apparatus is rather general and can be used for a wide range of temperatures
      between - 10 and 90 degrees C. The new apparatus is easy to use, inexpensive,
      simple to construct, and is designed for precise temperature control of oil
      immersion microscopy using epifluorescence. Thermal analysis of the experimental
      apparatus shows the effects of each of its components, as well as the effects of
      uncertainty in temperature measurements. Finally, results of this study indicate
      that: (i) embryos incubated and imaged at temperatures of 8 degrees C and below
      do not elongate; (ii) the initial elongation rate is strongly temperature
      dependent between 9 and 25 degrees C.

PMID- 10971803
TI  - New approximations for the variance in cavalieri sampling
AB  - The theory of Cavalieri sampling - or systematic sampling along an axis - has
      received a recent impetus. The error variance may be represented by the sum of
      three components, namely the extension term, the 'Zitterbewegung', and higher
      order terms. The extension term can be estimated from the data, and it
      constitutes the standard variance approximation used so far. The Zitterbewegung
      oscillates about zero, and neither this nor higher order terms have hitherto been
      considered to predict the variance. The extension term is always a good
      approximation of the variance when the number of observations is very large, but
      not necessarily when this number is small. In this paper we propose a more
      general representation of the variance, and from it we construct a flexible
      extension term which approximates the variance satisfactorily for an arbitrary
      number of observations. Furthermore, we generalize the current connection between
      the smoothness properties of the measurement function (e.g. the section area
      function of an object when the target is the volume) and the corresponding
      properties of its covariogram to facilitate the computation of the new variance
      approximations; this enables us to interpret the behaviour of the variance from
      the 'overall shape' of the measurement function. Our approach applies mainly to
      measurement functions whose form is known analytically, but it helps also to
      understand the behaviour of the variance when the measurement function is known
      at sufficiently many points; in fact, we illustrate the concepts with both
      synthetic and real data.

PMID- 10971804
TI  - Characterization of the cutting edge of glass knives for ultramicrotomy by
      scanning force microscopy using cantilevers with a defined tip geometry
AB  - The geometry of glass knife edges for ultramicrotomy was studied with nanoscale
      resolution using scanning force microscopy (SFM) in the contact mode. The local
      shape of the cutting edge was estimated from single line profiles of the SFM
      topographic images by taking into account the exact radius of the ultrasharp
      silicon tip. The tip radius was estimated from secondary electron micrographs
      recorded at low voltage by field emission scanning electron microscopy (FESEM).
      The radius of the investigated cutting edges was found to be in range 5-20 nm.
      The results obtained illustrate that the combination of SFM and high resolution
      FESEM provides a unique means to determine precisely the radius of glass knives.

PMID- 10971805
TI  - Thin sections for hard tissue histology: a new procedure.
AB  - We describe a simple method by which thin sections ( approximately 100 microm)
      from modern and archaeological teeth and bones can be obtained. A detailed
      embedding-cutting-mounting procedure is proposed, suggesting the use of a dental
      adhesive system, composite resins and conventional embedding resins, with the
      aims of improving the quality of the sections and substantially reducing the
      steps and time needed to prepare specimens for histological analysis. The
      introduction of this dental materials-based system allows an accurate positioning
      of the sample embedded inside the resin, prevents cracks and distortions of the
      section during the cutting phase and generally improves mounting sections on
      slides.

PMID- 10971806
TI  - The cause of Cushing's disease.

PMID- 10971807
TI  - Neuropeptide Y counteracts the anorectic and weight reducing effects of ciliary
      neurotropic factor.
AB  - Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily,
      has been shown to induce hypophagia and weight loss. Neuropeptide Y (NPY) and
      orexin are potent orexigenic signals in the hypothalamus. Anorexia, normally seen
      in response to infection, injury and inflammation, may result from diminished
      hypothalamic orexigenic signalling caused by persistently elevated cytokines,
      including CNTF. To test this hypothesis, we first examined the effects of chronic
      intracerebroventricular (i.c.v.) infusion of CNTF for 6-7 days on food intake and
      body weight as well as hypothalamic NPY and orexin gene expression in male rats.
      Subsequently, the effectiveness of NPY replacement to counteract the effects of
      CNTF by coinfusion of NPY and CNTF was evaluated. Chronic i.c.v. infusion of CNTF
      (2.5 microg/day) reduced body weight (14.3% vs control) at the end of 7 days.
      Food intake remained suppressed for 5 days postinfusion and subsequently
      gradually returned to the control range by day 7. Serum leptin concentrations in
      these rats were in the same range seen in control rats. Chronic i.c.v. infusion
      of higher doses of CNTF (5.0 microg/day) produced sustained anorexia and body
      weight loss (29% vs controls) through the entire duration of the experiment. This
      severe anorexia was accompanied by markedly suppressed serum leptin
      concentrations. Furthermore, CNTF infusion alone significantly reduced
      hypothalamic NPY gene expression (P < 0. 05) without affecting orexin gene
      expression. As expected, in fusion of NPY alone (18 microg/day) augmented food
      intake (191.6% over the initial control, P < 0.05) and produced a 25.1% weight
      gain in conjunction with a 10-fold increase in serum leptin concentrations at the
      end of the 7-day period. Interestingly, coinfusion of this regimen of NPY with
      the highly effective anorectic and body reducing effects of CNTF (5.0 microg/day)
      not only prevented the CNTF-induced anorexia and weight loss, but also normalized
      serum leptin concentrations and hypothalamic NPY gene expression. These results
      demonstrate that chronic central infusion to produce a persistent elevation of
      the cytokine at pathophysiological levels (a situation that may normally manifest
      during infection, injury and inflammation) produced severe anorexia and weight
      loss in conjunction with reduction in both serum leptin concentrations and
      hypothalamic NPY gene expression. Reinstatement of hypothalamic NPY signalling by
      coinfusion of NPY counteracted these CNTF-induced responses.

PMID- 10971808
TI  - Vasopressin and oxytocin neurones of hypothalamic supraoptic and paraventricular
      nuclei co-express mRNA for Type-1 and Type-2 corticotropin-releasing hormone
      receptors.
AB  - The presence of corticotropin-releasing hormone (CRH) receptors type-1 (CRHR-1)
      and type-2 (CRHR-2alpha) in the hypothalamic supraoptic (SON) and paraventricular
      (PVN) nuclei, and the effects of i.c.v. injection of CRH and urocortin on
      arginine vasopressin (AVP) and oxytocin release, have suggested that CRH ligands
      have a role in osmoregulation. In this study, double labelling in situ
      hybridization using 35S-labelled CRHR-1 or CRHR-2alpha and digoxigenin-labelled
      AVP, oxytocin or CRH riboprobes was employed to examine the localization of CRHR
      1 or CRHR-2alpha mRNA in the SON and PVN of control and osmotically stimulated
      rats. Rats received an i.p. hypertonic saline (1.5 M) injection or isotonic
      saline injection (controls), or 2% NaCl intake (salt loading) or tap water
      (controls) for 12 days. While CRHR-1 mRNA was undetectable in the SON and PVN in
      control rats, its expression was increased markedly at 4 h after i.p. hypertonic
      saline injection or after 12 days salt loading. Of the cells labelled with
      digoxigenin-AVP, 53% in the SON and 90% in the PVN coexpressed CRHR-1 mRNA after
      i.p. hypertonic saline injection. In oxytocinergic neurones, 73% in the SON and
      91% in the PVN showed CRHR-1 autoradiographic grains higher than background
      levels after i.p. hypertonic saline injection. In addition, i.p. hypertonic
      saline induced CRHR-1 mRNA expression in digoxigenin-CRH stained cells in the
      parvocellular PVN. CRHR-2alpha transcripts were present in both the SON and PVN
      under basal conditions, and salt loading, but not acute i.p. hypertonic saline
      injection, further stimulated this expression. Double labelling in situ
      hybridization showed colocalization of CRHR-2alpha mRNA with AVP and oxytocin
      mRNA in the SON. These studies support a role for CRH and urocortin regulating
      the hypothalamo-neurohypophyseal system, and suggest a direct action of the
      peptides in the magnocellular neurones.

PMID- 10971809
TI  - Permissive effect of centrally administered oxytocin on the excitatory response
      of oxytocin neurones to ventral tegmental stimulation in the suckled lactating
      rat.
AB  - The mesencephalic ventral tegmentum has been implicated in the milk-ejection
      reflex and modulation of inputs from this region could provide a mechanism
      whereby central oxytocin facilitates synchronous bursting of oxytocin neurones
      during suckling. Experiments were therefore undertaken to investigate the effect
      of intracerebroventricular (i.c.v.) oxytocin on the response of oxytocin neurones
      to ventral tegmental stimulation. Oxytocin neurones were recorded in the
      supraoptic nucleus of urethane-anaesthetized lactating rats during suckling, and
      their response to single shock stimulation of the ventral tegmentum was monitored
      using peri-stimulus time-interval histograms. Before i.c.v. oxytocin, oxytocin
      neurones were either unresponsive to ventral tegmental stimulation, or displayed
      a small inhibition. However, after administration of oxytocin (2.2 ng i.c.v.),
      seven out of eight neurones tested displayed a pronounced excitatory response
      (onset latency 78.4 +/- 4.8 ms, duration 73.4 +/- 8.3 ms). This permissive effect
      on the excitatory response was only observed in the presence of suckling, and
      followed the same time course as facilitation of the milk-ejection reflex, being
      maximal immediately before each facilitated bursting response in the oxytocin
      neurones. The response to ventral tegmental stimulation remained unaltered after
      intraperitoneal administration of hypertonic saline to cause a generalized
      increase in the excitability of the oxytocin neurones. Moreover, i.c.v. oxytocin
      had no effect on the response of oxytocin neurones to stimulation of a descending
      input from the medial septum. In conclusion, administration of i.c.v. oxytocin
      has a selective permissive effect on the excitation of oxytocin neurones from the
      ventral tegmentum, and this supports previous in vitro studies suggesting that
      centrally released oxytocin may act as a modulator of afferent transmission to
      the magnocellular nuclei. This effect on the afferent excitation of oxytocin
      neurones may provide a mechanism whereby i.c.v. oxytocin facilitates suckling
      evoked bursting activity.

PMID- 10971810
TI  - Ontogeny of aromatase and tyrosine hydroxylase activity and of aromatase
      immunoreactive cells in the preoptic area of male and female Japanese quail.
AB  - The aromatization of testosterone into oestrogens plays a key role in the control
      of many behavioural and physiological aspects of reproduction. In the quail
      preoptic area (POA), aromatase activity and the number of aromatase
      immunoreactive (ARO-ir) cells are sexually differentiated (males > females). This
      sex difference is implicated in the control of the sexually dimorphic behavioural
      response of quail to testosterone. We analysed the ontogenetic development of
      this sex difference by measuring aromatase activity and counting ARO-ir cells in
      the POA of males and females from day 1 post hatch to sexual maturity. We
      investigated in parallel another enzyme: tyrosine hydroxylase, the rate limiting
      step in catecholamine synthesis. Between hatching and 4 weeks of age, aromatase
      activity levels were low and equal in males and females. Aromatase activity then
      markedly increased in both sexes when subjects initiated their sexual maturation
      but this increase was more pronounced in males so that a marked difference in
      aromatase activity was present in 6 and 8 week-old subjects. Tyrosine hydroxylase
      activity progressively increased with age starting immediately after hatching and
      there was no abrupt modification in the slope of this increase when birds became
      sexually mature. No sex difference was detected in the activity of this enzyme.
      The number of ARO-ir cells in the POA progressively increased with age starting
      at hatching. No sex difference in ARO-ir cell numbers could be detected before
      subjects reached full sexual maturity. The analysis of the three-dimensional
      organization of ARO-ir cells in the POA revealed that, with increasing ages, ARO
      ir cells acquire a progressively more lateral position: they are largely
      periventricular in young birds but they are found at higher density in the
      lateral part of the medial preoptic nucleus in adults. These data indicate that
      aromatase activity differentiates sexually when birds reach sexual maturity
      presumably under the activating effects of the increased testosterone levels in
      males. The number of ARO-ir cells, however, begins to increase in a non sexually
      differentiated manner before the rise in plasma testosterone in parallel with the
      increased tyrosine hydroxylase activity. Whether this temporal coincidence
      results from a general ontogenetic pattern or from more direct causal links
      remains to be established.

PMID- 10971811
TI  - Differential mRNA expression of the two mineralocorticoid receptor splice
      variants within the human brain: structure analysis of their different DNA
      binding domains.
AB  - In human brain tissue, cortisol action, at basal concentrations, is mediated by
      the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA
      binding domain due to alternative splice site usage between exons 3 and 4 results
      in an MR mRNA splice variant (MR+4) encoding a receptor protein with four
      additional amino acids compared to the wild-type MR protein. To elucidate the
      questions of sex, age, and/or tissue dependent differences of the relative amount
      of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from
      temporal and frontal lobe or hippocampus. One hundred and twenty samples were
      obtained from patients with epilepsy and 11 samples from patients with brain
      tumours. A small but significant difference of the MR+4 mRNA splice variant
      proportions in cortex (9.5 +/- 0.8%) and subcortical white matter (6.6 +/- 0.7%)
      of the temporal lobe could be detected, indicating differential MR splice variant
      expression within these brain areas. Moreover, the splice variant ratios in
      samples of the temporal lobe cortex collected from patients with epilepsy
      differed from samples of patients with brain tumours. These data point to an
      altered expression of the MR splice variants in epilepsy, and strengthen the
      supposition of a tissue specific alternative splicing of the MR mRNA. The
      frequent occurrence of the MR+4 transcript raises the question of its functional
      significance. For this reason, an MR+4 DNA-binding-domain structure model was
      generated by computer-based homology modelling based on the known glucocorticoid
      receptor structure. The data obtained revealed no distorting effect of the
      inserted four amino acids on the adjacent secondary structures, thereby
      suggesting that both zinc fingers retain their function. The resulting structure
      of the MR+4 model leads to the supposition that the receptor retains its
      function. Moreover, databank analysis with respect to this kind of steroid
      receptor variation and our own sequence data of the closely related progesterone
      receptor sustained the hypothesis that only corticosteroid receptors were
      affected by this alternative splicing event.

PMID- 10971812
TI  - The effect of the alpha-2-adrenergic agonist, clonidine, on secretion patterns
      and rates of adrenocorticotropic hormone and its secretagogues in the horse.
AB  - Alpha-2-adrenoceptor activation may lower adrenocorticotropic hormone (ACTH) by
      reducing secretagogue input and/or increasing the release of an inhibitory factor
      (CIF). To investigate this, we gave clonidine, an alpha-2-agonist, to seven
      horses, and collected pituitary venous blood every minute for 20 min before
      treatment and 40 min after treatment. Six horses were given saline vehicle. Mean
      secretion rates of corticotrophin-releasing hormone (CRH), arginine vasopressin
      (AVP) and ACTH were calculated before and during four 5-min then two 10-min
      periods after clonidine or saline. Reduction in ACTH secretion without
      corresponding changes in CRH and/or AVP would imply the presence of CIF.
      Secretion rates of ACTH (P = 0.008) and AVP (P = 0.0005) fell after clonidine and
      remained lower than baseline values for 20 min and 10 min, respectively. The CRH
      secretion rate decreased slightly but not significantly after clonidine. In
      controls, hormone secretion rates did not alter during the experiment. Multiple
      linear regression showed that CRH and AVP secretion accounted for 69% (treated)
      or 45% (controls) of the variation in ACTH secretion (P < 0.0001 for each). CRH
      alone contributed 80% (treated) or 76% (controls) of the fit to this model, which
      is consistent with the concept that CRH 'sets the gain' of the response of
      corticotrophs to fluctuations in AVP. Accordingly, minute-to-minute changes in
      pituitary concentrations of AVP and ACTH were synchronous when all data were
      considered (% concordant changes: controls, 68%, P < 0.0001; treated, 76%, P <
      0.0001) and the percentage of concordant movement was unaffected by clonidine
      (before 72%; after 73%; P = 0.80). In treated horses but not controls, the ratio
      between the secretion rates of ACTH and AVP fell (P = 0.009), while the ACTH :
      CRH ratio tended to fall after clonidine, implying reduced responsiveness to
      stimulation. Moreover, one horse showed a drop in ACTH and a rise in CRH and AVP
      secretion after clonidine. We conclude that in horses alpha-2-adrenoceptor
      activation lowers ACTH secretion primarily by reducing the secretion of AVP and
      possibly CRH. While there was some evidence that a CIF may participate in the
      clonidine-induced suppression of ACTH, the subtlety of the discordance between
      ACTH and its secretagogues in most horses and the rarity of complete dissociation
      indicate that it does not play a major role.

PMID- 10971814
TI  - Effects of gonadal steroids on brain serotonergic and aromatase activity during
      the critical period of sexual differentiation in tilapia, Oreochromis
      mossambicus.
AB  - The effects of gonadal steroids on brain serotonin (5-HT) and aromatase activity
      during the critical period of sexual differentiation were investigated in
      tilapia, Oreochromis mossambicus. Treatment of tilapia with 17beta-oestradiol
      (E2) between days 7 and 10 posthatching resulted in a significant increase in the
      female : male ratio as determined at day 90, and a significant reduction in brain
      5-HT content. Treatment between days 10 and 20, or between days 20 and 30, had no
      significant effect. Since the 5-HT system may influence sexual differentiation,
      we examined the effects of para-chlorophenylalanine (p-CPA), a 5-HT synthesis
      inhibitor. As with E2, treatment of tilapia with p-CPA between days 7 and 10
      posthatching resulted in a significant increase in the female : male ratio.
      Again, treatment between days 10 and 20, or between days 20 and 30, had no
      significant effect. Both p-CPA and E2 significantly depressed brain aromatase
      activity when administrated between days 7 and 10, but not subsequently. In
      tilapia treated between days 7 and 10, the brain 5-HT content was lowered by E2
      to an extent similar to that seen with p-CPA, which is consistent with the
      suggestion that the effect of E2 on sexual differentiation may be mediated by the
      5-HT system. Treatment of tilapia with 17alpha-methyltestosterone (MT), by
      contrast, resulted in a reduction in the female : male ratio, and treatment was
      most effective when given between days 10 and 20. The period of maximal effect of
      MT upon sex ratio appears to coincide with the ability of MT to induce an
      increase in brain aromatase activity.

PMID- 10971813
TI  - Rat adrenal transplants are reinnervated: an invalid model of denervated adrenal
      cortical tissue.
AB  - Adrenal autotransplantation is a widely used approach to investigate the
      potential for neural modulation of adrenal cortical function. It is believed that
      regenerating adrenal transplants are not reinnervated, thereby providing a model
      to investigate adrenal function in the absence of neural modulation. However, the
      hypothesis that adrenal transplants become reinnervated has not been directly
      tested. The purpose of the present study was to characterize the time course,
      extent, and nature of the reinnervation of the regenerating adrenal transplant
      and to assess whether the recovery of steroidogenic function and enzyme
      expression correlates temporally with the presence of innervation. Using
      immunohistofluorescent detection of tyrosine hydroxylase (TH), neuropeptide Y
      (NPY), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide
      (VIP), the innervation of regenerating adrenals was assessed 14-30 days after
      transplantation of adrenal capsules beneath the kidney capsule in rats. Extensive
      reinnervation by TH-, NPY-, and VIP-positive fibres was present by 14 days after
      transplantation including regions of the adrenal capsule and cortex, with only
      minimal reinnervation by CGRP-positive fibres up to 30 days. TH- and NPY-positive
      chromaffin cells were also observed in the regenerating transplants. In addition,
      there was marked recovery of steroidogenic function and steroidogenic enzyme
      expression up to 30 days. The finding that nerve fibres are present in the
      transplants during the re-establishment of steroidogenic function and enzyme
      expression suggests that innervation may modulate the regeneration and functional
      recovery of adrenal transplants. In an attempt to prevent reinnervation of
      transplants, adrenal capsules were autotransplanted to denervated kidneys.
      Immunohistochemical analysis showed that, despite extensive denervation of the
      kidney tissue, the reinnervation and regeneration of the adrenal transplants
      still occurred. These data demonstrate the marked capacity of the regenerating
      adrenal to become reinnervated and reinforces the conclusion that adrenal
      transplants are an invalid model of denervated adrenal cortical tissue.

PMID- 10971815
TI  - Oestrogen upregulates noradrenaline release in the mediobasal hypothalamus and
      tyrosine hydroxylase gene expression in the brainstem of ovariectomized rhesus
      macaques.
AB  - Noradrenaline plays a key role in the initiation of ovulation in nonprimate
      species. A similar noradrenaline role in the primate has not been established
      experimentally. We utilized the ovariectomized-oestrogen-supplemented (OVX + E)
      rhesus macaque to examine the effects of intravenous (i.v.) infusion of
      oestradiol-17beta (E2) on the activity of the brain noradrenaline system.
      Experiment 1 established the induction of a preovulatory surge-like release of
      luteinizing hormone in OVX + E monkeys by i.v. infusion of E2 (OVX + E + E2). In
      experiment 2, a marked increase in hypothalamic microdialysate noradrenaline
      concentrations occurred after identical E2 infusion into the OVX + E monkeys that
      were used in experiment 1. In experiment 3, tyrosine hydroxylase (TH) mRNA
      expression in the locus coeruleus of the brainstem increased at various times
      after E2 infusion as determined by semiquantitative in situ hybridization. The
      amount of TH mRNA in OVX + E + E2 animals was higher (P < 0.05) than that in
      either the OVX + E or OVX monkeys; no difference was found in the latter two
      groups. Moreover, selected locus coeruleus sections from E2-infused monkeys were
      examined for the localization of oestrogen receptors (ER) by in situ
      hybridization. Both ER-alpha and ER-beta mRNAs were expressed in the locus
      coeruleus, although the expression was greater for ER-alpha than for ER-beta. We
      conclude that i.v. infusion of E2, which induces a preovulatory surge-like
      release of LH, stimulates brain noradrenaline activity; this enhanced activity
      likely involves an ER-mediated process and is reflected by hypothalamic
      noradrenaline release and locus coeruleus TH mRNA expression. The results support
      the concept that noradrenaline can influence the E2-stimulated ovulation in
      nonhuman primates and that the brainstem is one of the components in this
      neuroendocrine process.

PMID- 10971816
TI  - Role of protein kinases in the prolactin-induced intracellular calcium rise in
      Chinese hamster ovary cells expressing the prolactin receptor.
AB  - There is still only limited understanding of the early steps of prolactin signal
      transduction in target cells. It has been shown that prolactin actions are
      associated with cell protein phosphorylation, Ca2+ increases, and so on. However,
      the link between the activation of kinases and calcium influx or intracellular
      Ca2+ mobilization has not yet been clearly established. Chinese hamster ovary
      (CHO) cells, stably transfected with the long form of rabbit mammary gland
      prolactin receptor (PRL-R) cDNA were used for PRL-R signal transduction studies.
      Spectrofluorimetric techniques were used to measure intracellular calcium
      ([Ca2+]i) in cell populations with Indo1 as a calcium fluorescent probe. We
      demonstrate that, although protein kinase C activation (PMA or DiC8) caused a
      calcium influx in CHO cells, prolactin-induced PKC activation was not responsible
      for the early effect of prolactin on [Ca2+]i. Activation of protein kinase A
      (PKA) or protein kinase G did not modify [Ca2+]i and inhibition of PKA pathway
      did not affect the prolactin response. In the same way, phosphatidylinositol-3
      kinaseinhibition had no effect on the prolactin-induced Ca2+ increase. On the
      other hand, tyrosine kinase inhibitors (herbimycin A, lavendustin A, and
      genistein) completely blocked the effect of prolactin on [Ca2+]i (influx and
      release). W7, a calmodulin-antagonist, and a specific inhibitor of calmodulin
      kinases (KN-62), only blocked prolactin-induced Ca2+ influx but had no
      significant effect on Ca2+ release. Using pharmacological agents, we present new
      data concerning the involvement of protein phosphorylations in the early effects
      of prolactin on ionic channels in CHO cells expressing the long form of PRL-R.
      Our results suggest that, at least in the very early steps of prolactin signal
      transduction, serine-threonine phosphorylation does not participate in the
      prolactin-induced calcium increase. On the other hand, tyrosine phosphorylation
      is a crucial, very early step, since it controls K+ channel activation, calcium
      influx, and intracellular calcium mobilization. Calmodulin acts later, since its
      inhibition only blocks the prolactin-induced Ca2+ influx.

PMID- 10971817
TI  - Differential in vitro secretion of gonadotropin-releasing hormone (GnRH) and
      [hydroxyproline]GnRH from the rat hypothalamus during postnatal development.
AB  - The differential secretion of gonadotropin-releasing hormone (GnRH) and
      [hydroxyproline9]GnRH (HypGnRH) has been recently reported from the adult rat
      hypothalamus. We report here in vitro cosecretion of HypGnRH and GnRH by the
      hypothalamus of 2-45 day-old-rats and provide evidence that they are
      differentially regulated throughout development. The secretion of both forms of
      GnRH was increased in a dependent manner during depolarization by high K+
      solutions, and was stimulated by forskolin and 12-O-tetradecanoylphorbol-13
      acetate (TPA), activators of adenylate cyclase and protein kinase C pathways,
      respectively. The proportion of HypGnRH in the release of GnRH-like peptides
      remained stable and high (33-40%) under basal and K+-induced conditions until
      days 13 and 21, respectively. By contrast, the proportion of HypGnRH in the total
      GnRH-like content of the developing hypothalamus continuously decreased (from 37%
      to 14%). Similarly, the proportion of HypGnRH: total GnRH-like material released
      remained stable in TPA- (30%) and forskolin- (50%) induced secretion until
      postnatal day 8. Evaluation of release over tissue store ratios revealed a 1.3-to
      2.8-fold higher release of HypGnRH compared to GnRH according to the different
      secretions and postnatal periods examined. The preferential recruitment of
      HypGnRH was maintained under basal and K+ conditions during postnatal
      development, but it disappeared under TPA stimulation from day 13 onwards. After
      forskolin stimulation, the preferential mobilization of HypGnRH was markedly
      reduced from day 2 to day 13 but recovered its high perinatal level during
      puberty. Taken together, our results support the hypothesis that HypGnRH may play
      a specific role in development. In addition, a specific function of this peptide
      taking place during puberty through the activation of the adenylate cyclase
      pathway is suggested.

PMID- 10971818
TI  - Nuclear receptor coactivators in neuroendocrine function.
AB  - Steroid hormones influence a variety of neuroendocrine events, including brain
      development, sexual differentiation and reproduction. Hormones elicit many of
      these effects by binding to neuronal steroid receptors, which are members of a
      nuclear receptor superfamily of transcriptional activators. However, the
      mechanisms by which activated steroid receptors regulate gene expression in brain
      are not well understood. Recently, a new class of proteins, known as nuclear
      receptor coactivators, have been found to dramatically enhance steroid receptor
      mediated transactivation of genes in vitro. Here, the proposed molecular
      mechanisms of how these coactivators enhance the transcriptional activity of
      steroid receptors are summarized. While much is known about the mechanisms of
      these coactivators in vitro, it is unclear how these cofactors function in
      hormone action in vivo or in the brain. This paper discusses some of the initial
      and enticing investigations into the role of these important coregulatory
      proteins in neuroendocrine events. Finally, some of the critical issues and
      future directions in nuclear receptor coactivator function in neuroendocrinology
      are highlighted.

PMID- 10971819
TI  - How can the cellular immune response control hepatitis B virus replication?
AB  - In this review we focus on aspects of the virus-specific cellular immune
      response, although we should point out that all the components of the innate and
      adaptive immune response are likely to play a role in successful control of
      hepatitis B virus (HBV) infection. We concentrate particularly on the relevance
      of the polyclonality and multispecificity of the HBV-specific cytotoxic T cell
      response to its antiviral activity. In this context, we discuss the possible role
      of viral escape mutations and highlight evidence from other models of the benefit
      of multispecificity in antiviral responses. We stress the contribution of CD4
      help for effective CD8 responses and raise the possibility that HBV may produce
      factors inhibiting the antiviral response.

PMID- 10971820
TI  - Treatment of chronic hepatitis C virus infection in patients with cirrhosis.
AB  - Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20-30%
      of patients and to hepatocellular carcinoma (HCC) in 1-5% of patients. Rates of
      sustained virological response with standard interferon-alpha (IFN-alpha) are low
      in patients without cirrhosis (generally < 20%) and are even lower in those with
      cirrhosis. Combination therapy with IFN and ribavirin improves response rates in
      patients with chronic hepatitis C without cirrhosis, and the results from
      subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are
      encouraging. Importantly, treatment with IFN slows progression of liver fibrosis,
      regardless of HCV genotype or early response to therapy, and reduces the risk of
      HCC by two- to fivefold. The risk of development of HCC is also lower in patients
      who show at least a partial response to IFN therapy compared with those who show
      no response. There is a clear need for more definitive studies of treatment in
      patients with chronic hepatitis C and cirrhosis, ideally using therapies with
      greater efficacy. Nonetheless, based on the potential to slow the progression of
      liver fibrosis (regardless of treatment response) and to reduce the risk of HCC,
      a greater number of HCV-infected patients with cirrhosis should be considered as
      candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have
      improved virological response rates and may have additional clinical benefits in
      the prevention or reduction of fibrosis and retardation of progression of
      cirrhosis and HCC in these patients.

PMID- 10971821
TI  - RNA-dependent RNA polymerase activity encoded by GB virus-B non-structural
      protein 5B.
AB  - Phylogenetic analysis and polyprotein organization comparison have shown that GB
      virus-B (GBV-B) is closely related to hepatitis C virus (HCV). In this study, the
      coding region for GBV-B non-structural protein 5B (NS5B) was isolated by reverse
      transcription-polymerase chain reaction (RT-PCR) from pooled serum of GBV-B
      infected tamarins. Expression of soluble GBV-B NS5B protein in Escherichia coli
      was achieved by removal of a 19-amino acid hydrophobic domain at the C-terminus
      of the protein. The truncated GBV-B NS5B (NS5BDeltaCT19) was purified to
      homogeneity and shown to possess an RNA-dependent RNA polymerase (RdRp) activity
      in both gel-based and scintillation proximity assays. NS5BDeltaCT19 required the
      divalent cation Mn2+ for enzymatic activity, at an optimal concentration of 15
      mM. Interestingly, Mg2+, at concentrations up to 20 mM, did not support the GBV-B
      NS5B activity. This differs from HCV NS5B where both Mn2+ and Mg2+ can support
      RdRp activity. Zn2+ was found to inhibit the activity of GBV-B NS5B, with a 50%
      inhibitory concentration (IC50) of 5-10 microM. Higher concentrations of
      monovalent salts (NaCl or KCl > 100 mM) and glycerol (> 3%) were also inhibitory.
      NS5BDeltaCT19 was able to bind to RNA homopolymers, but utilized most efficiently
      poly(C), the one with the lowest binding affinity for RNA synthesis. Mutational
      analysis of GBV-B NS5B demonstrated the importance of several conserved sequence
      motifs for enzymatic activity. Based on sequence homology ( approximately 37%
      identity and 52% similarity) between GBV-B and HCV NS5B proteins, the active GBV
      B RdRp provides a good surrogate assay system for HCV polymerase studies.

PMID- 10971822
TI  - Clinical characteristics of patients with chronic hepatitis C showing biochemical
      remission, without hepatitis C virus eradication, as a result of interferon
      therapy. The Osaka Liver Disease Study Group.
AB  - During long-term follow-up of patients chronically infected with the hepatitis C
      virus (HCV) and treated with interferon (IFN), we identified some who had
      persistent normalization of serum alanine aminotransferase (ALT) but remained
      positive for HCV RNA. The aims of this study were to clarify the characteristics
      of these patients and to examine their clinical outcome after treatment. Nine
      hundred and ninety-eight patients treated with IFN were followed-up biochemically
      and virologically, and by liver ultrasound, for 13-95 months. A short-term
      biochemical sustained response, where ALT remained within the normal range for 6
      months after the completion of IFN therapy, was found in 296 patients; in 240 of
      these patients serum HCV RNA remained undetectable during long-term follow-up.
      The rate of HCV RNA persistence was 7.09 times greater in short-term biochemical
      sustained responders with a high viral load than in those with a low viral load
      (P=0.0001, odds ratio [OR]=7.09), and 3. 70-fold lower in those treated with a
      large dose of IFN than in those treated with a small dose (P=0.02, OR=0.27).
      Thirty-three (59%) of 56 patients without HCV eradication showed continuous ALT
      normalization for 26-80 months after cessation of IFN therapy. Short-term
      biochemical sustained responders who were older (P=0.009, OR=10.43) and who were
      male (P=0.03, OR=6.98) had a significantly greater probability of maintaining a
      normal ALT level, even when serum HCV RNA was positive. When the incidence of HCC
      was investigated during long-term follow-up in patients without HCV eradication,
      it was found to be significantly lower in patients with persistently normal ALT
      levels than in those with abnormal ALT levels (P=0.03). Hence, when HCV is not
      eradicated as a result of IFN therapy, it may induce a long-term carrier state of
      HCV infection with normal ALT levels in older or male patients, in whom the
      cumulative incidence of HCC is markedly decreased.

PMID- 10971823
TI  - Sustained response to interferon-alpha2a monotherapy of young blood donors with
      minimal-to-mild chronic hepatitis C. The Donor Surveillance Study Group.
AB  - Subjects with minimal-to-mild chronic hepatitis C may suffer long-term
      consequences of hepatitis C virus (HCV) infection. Nonetheless, they are not
      candidates for antiviral treatment, mainly because little data are available
      concerning the efficacy and safety of therapy. Thirty-two HCV RNA positive
      individuals aged 18-45 years, who had a histological activity index score < or =
      8 and alanine aminotransferase (ALT) levels < or = 1.5 times lower than the
      normal limit for at least 1 year, were prospectively enrolled among a cohort of
      35358 candidate blood donors, and treated with 4.5 mega units (MU) of recombinant
      interferon-alpha2a (IFN-alpha2a) thrice weekly for 6 months, and for an
      additional 6 months if a virological response was observed. Twelve months after
      the completion of treatment, 13 of 31 evaluable patients were HCV RNA negative,
      accounting for a sustained response rate of 42%. Patients without fibrosis had a
      lower response rate than those with mild fibrosis (two of 14 vs 11 of 17;
      P=0.012). In responders, median aminotransferase levels were significantly lower
      after therapy than before (11.04 +/- 3.98 vs 27.3 +/- 12.32 U l-1, respectively;
      P < 0. 005). When the analysis was limited to the six responders whose
      pretreatment aminotransferase levels were consistently normal, this difference
      was still significant (9.33 +/- 4.12 vs 20.58 +/- 6.73 U l-1; P=0.002). In
      conclusion, a durable suppression of viraemia can be obtained by IFN monotherapy
      in a relatively high proportion of young subjects with minimal-to-mild chronic
      hepatitis C, especially when portal fibrosis is found on liver biopsy. The
      disappearance of viraemia always leads to a reduction in the degree of
      hepatocellular necrosis.

PMID- 10971824
TI  - Health care, treatment patterns and cost of services for patients infected with
      chronic hepatitis C virus in a large insured New England population.
AB  - The purpose of this study was to describe the cost of health care and the
      patterns of treatment of young patients (under 65 years of age) identified in
      health insurance claims as having received services for chronic hepatitis C virus
      (HCV) infection. We screened computerized claims from a US indemnity and managed
      care organization for out-patient and in-patient diagnoses related to HCV.
      Treatment patterns and costs of services were evaluated in the following sites of
      care: in-patient care, emergency room, hospital out-patient care, ambulatory
      office care and pharmaceuticals. There were 191 patients with chronic HCV-related
      claims in this study population (25 per 100 000), during 1995-97. Medical
      services and pharmaceutical costs in total (US$ 7.1 million) constituted a
      considerable cost in patients with chronic HCV-related claims during 1995-97. A
      subset of 98 patients were prescribed interferon-alpha with substantial
      variability in treatment regimens. Claims data provides a unique opportunity to
      estimate dollars paid for treatment patterns and health services in a 'real
      world' insured population and contributes to the understanding of health services
      for chronic HCV.

PMID- 10971825
TI  - Comparative analysis of amino acid sequences from envelope proteins isolated from
      different hepatitis C virus variants: possible role of conservative and variable
      regions.
AB  - Sequences of the E1 and E2 envelope proteins of hepatitis C virus (HCV) (827 non
      identical items) were collected from available sources and aligned. Analysis of
      the alignment identified regions with different sequence variability. It was
      found that 33% and 50% of positions within E1 and E2, respectively, were highly
      conservative. Such conservation can be considered as the minimum for maintaining
      stability of the three-dimensional structure and function of these proteins.
      Conserved cysteines in E1 and E2 (eight and 18 residues, respectively) were
      presumed to form intramolecular disulphide bonds. Both envelope proteins were
      predicted to contain 14 conservative glycosylation sites. Two additional
      glycosylation sites were predicted in 58% of E1 and 30% of E2 sequences within
      the corresponding regions. We describe the positions of six conservative regions
      in E1 and E2, which have several charged and aromatic residues known to
      participate frequently in protein-protein recognition. Peculiarities in the amino
      acid content of conservative fragments and putative differences in glycosylation
      were considered with regard to antigenic specificity and possible binding to
      surface structures of target cells. We also analysed the hypervariable region 1
      (HVR1), located in the E2 protein. Aligned positions of HVR1 were described in
      relation to the maintenance of conformational stability and recognition of cell
      receptors.

PMID- 10971826
TI  - Molecular analysis of hepatitis D virus infection in Miyako Island, a small
      Japanese island.
AB  - The present investigation attempted to determine the exact prevalence of
      hepatitis D virus (HDV) infection among inhabitants of Miyako Island (a remote
      island in the Okinawa Prefecture) and the molecular characteristics of the HDV
      genome that was isolated. Among the 4728 inhabitants, 375 (7.9%) were hepatitis B
      surface antigen (HBsAg) positive. Antibody to HDV (anti-HDV) was present in 32
      (8. 5%) of these 375 subjects, and liver function tests were normal in most
      subjects. The presence of HDV RNA was analysed by nested polymerase chain
      reaction (PCR). Thirteen out of the 32 anti-HDV antibody-positive subjects were
      HDV RNA positive. Thus, 3.5% of HBsAg-positive subjects on Miyako Island were HDV
      RNA positive. Among the HDV RNA-positive subjects, liver function tests were
      within normal limits or were mildly abnormal. Nucleotide sequence analysis
      revealed that the HDV genomes on Miyako Island were similar to the Japanese and
      Taiwan isolates of HDV genotype II. Taiwan is geographically close to Miyako
      Island. Even though the races are different, a geographical factor was revealed
      to be significant with regard to HDV infection, which was spread in a closed
      environment.

PMID- 10971827
TI  - Interferon-alpha therapy in chronic hepatitis B: early monitoring of hepatitis B
      e antigen may help to decide whether to stop or to prolong therapy.
AB  - Hepatitis B e antigen (HBeAg) was quantified before, during and after interferon
      alpha administration in a trial of 162 chronic hepatitis B patients treated for
      16 or 32 weeks. In 139 of these patients we examined the prognostic value of the
      pretreatment level of HBeAg and the reduction in HBeAg level at weeks 4 and 8 for
      response at week 16. Multivariate analysis showed that the HBeAg pretreatment
      level is a highly significant predictor of response (judged as HBeAg and
      hepatitis B virus [HBV] DNA negativity), followed by a decrease in HBeAg from the
      start of therapy to week 8. During the first 8 weeks of therapy, a decrease in
      HBeAg of less than 40%, as observed in 30% of the patients, consistently resulted
      in non-response. After 16 weeks of treatment, non-responding patients were
      randomly assigned to receive no further treatment (n=57) or prolonged treatment
      for another 16 weeks (n=61). In both groups, changes in the HBeAg level from the
      start of (the first) therapy to week 8, but not the pretreatment HBeAg level
      itself, were significantly related to the response at week 52 (the end of follow
      up). Changes in the HBV DNA level had no additional predictive value for response
      at weeks 16 or 52. Therefore, instead of sequential HBV DNA assessment, we
      recommend monthly monitoring of HBeAg during IFN-alpha therapy.

PMID- 10971828
TI  - Evaluation of an enzyme-linked immunosorbent assay for detection and
      quantification of hepatitis B virus PreS1 envelope antigen in serum samples:
      comparison with two commercial assays for monitoring hepatitis B virus DNA.
AB  - An in-house sensitive and easy-to-use solid-phase enzyme-linked immunoassay
      (ELISA) was adapted for the detection and quantification of hepatitis B virus
      (HBV) PreS1 envelope antigen in serum, and compared with the HBV DNA Hybrid
      Capturetrade mark system from Murex and the polymerase chain reaction (PCR)
      Amplicortrade mark HBV Monitor assay from Roche. Twenty-five patients with
      chronic hepatitis B after liver transplantation were included in this study. The
      sensitivity of our ELISA was found to be 50 pg of HBsAg/PreS1Ag ml-1. The
      linearity was between 0.1 and 100 ng ml-1. Intra-assay reproducibility was
      obtained with a standard deviation of <1%. No correlation between the presence of
      serum PreS1 antigen and viral DNA detected by direct hybridization (Murex) was
      observed. In contrast, there was a significant 96% correspondence in the presence
      of PreS1 antigen and viral DNA detected and quantified by the PCR assay (Roche).
      In conclusion, the most important and reliable markers for monitoring residual
      HBV replication in serum were HBV DNA by the PCR assay, and virus envelope
      PreS1Ag by our in-house ELISA. Thus, PreS1Ag disappearance in serum could be used
      for evaluating the efficacy of antiviral therapies.

PMID- 10971829
TI  - Subacute thyroiditis during treatment with combination therapy (interferon plus
      ribavirin) for hepatitis C virus.
AB  - Autoimmune thyroiditis has been frequently reported during interferon monotherapy
      for hepatitis C, but there are few reports concerning subacute thyroiditis.
      Recently, combination therapy of IFN plus ribavirin has become the preferred
      therapeutic schedule for chronic hepatitis C. Similarly to interferon
      monotherapy, there are no reports concerning subacute thyroiditis during
      combination therapy. We described four episodes of subacute thyroiditis occurring
      in three patients during antiviral combination therapy. All patients had symptoms
      compatible with hyperthyroidism, which could be misdiagnosed as IFN side-effects.
      The antiviral treatment was continued in all three patients and thyroid function
      increased progressively with pharmacological treatment for hyperthyroidism. We
      concluded that subacute thyroiditis may be a complication of combination
      antiviral therapy and should be investigated in patients presenting with
      compatible symptoms, in order to differentiate from IFN side-effects.

PMID- 10971830
TI  - [Iron deficiency towards the year 2000].
AB  - This is a non-comprehensive overview of the latest 50 years about the evolution
      of iron metabolism and the methodology we currently have for the diagnosis of
      iron deficiency and its effects on human health. In the 40's iron absorption was
      determined by chemistry. The amount of iron absorbed was calculated as the
      difference between dietary iron and excreted iron. The other methods used to
      measure dietary iron was hemoglobin repletion. In the 70's the measurement of
      plasmatic ferritin was an important contribution to iron metabolism to assess
      iron deficiency and iron overload. In the same decade the extrinsic and intrinsic
      labelled methodology was an important advancement. The 70's and 80's were years
      where scientists aimed at finding iron absorption inhibitors, namely coffee,
      calcium, tea, zinc and fiber. The 80's and 90's were characterized for the
      emerging knowledge an iron absorption from a food, a meal and a complete diet and
      for the favorable effect of food iron fortification in developing countries. Also
      for the effect of iron excess in overall health and myocardial infarction in
      developed countries were studied.

PMID- 10971831
TI  - The nutritional assessment of iron status.
AB  - In nutritional studies to assess the prevalence of iron deficiency, it has been
      common practice to define 3 stages of increasing severity: iron storage depletion
      as defined by low serum ferritin, mild iron deficiency without anemia based on
      laboratory evidence of iron deficient erythropoiesis (IDE), and overt iron
      deficiency anemia (IDA). While this approach provides a broad perspective of
      impaired iron status, the main liabilities of iron lack are associated only with
      the more advanced stage of IDA. Consequently, the hemoglobin determination can be
      used to screen for nutritionally significant iron deficiency. Having identified
      anemia, more specific laboratory studies are needed to establish iron lack as the
      cause. The traditional measurements of iron deficient erythropoiesis (IDE) such
      as a low transferrin saturation, elevated erythrocyte protoporphyrin, or
      decreased mean corpuscular volume are commonly used. The major drawback in using
      these parameters is that they are affected similarly in individuals with the
      anemia of chronic disease (ACD), a common form of anemia in low socioeconomic
      populations. Because iron stores are invariably absent in individuals with
      uncomplicated IDA, a low serum ferritin concentration below 20 micrograms/L
      confirms the diagnosis of IDA when anemia is present. The main limitation of the
      serum ferritin is that it is falsely elevated to within the normal range when IDA
      develops in individuals with concurrent infection or chronic inflammation. When
      this occurs in a clinical setting, a bone marrow examination is commonly
      performed to identify IDA. Recent investigations indicate that this cumbersome
      procedure can be avoided by measuring an important new iron-related measurement,
      the serum transferrin receptor (TfR). Because the synthesis of TfR is upregulated
      with tissue iron deficiency, IDA can be identified readily by an elevated serum
      TfR. Importantly, the serum TfR is normal in individuals with the ACD but becomes
      elevated if these individuals develop IDA. The optimal combination of laboratory
      measurements for detecting IDA is the hemoglobin, serum ferritin and serum TfR.

PMID- 10971832
TI  - Iron supplementation as a strategy for the control of iron deficiency and
      ferropenic anemia.
AB  - Iron supplementation is a public health strategy designed for the prevention of
      iron deficiency and its consecutive anemia. It should be targeted, safe,
      flexible, long term and ideally, community based under the supervision of the
      health sector. It must be differentiated from iron therapy, even though, in the
      intermediate and long term it corrects mild-moderate deficiency of iron and
      ferropenic anemia. It should complement other measures for the control of iron
      deficiency. A summary of results comparing daily and intermittent iron
      supplementation (every 3-days in rats, and weekly in humans) is presented,
      including studies in an animal model, human supplementary-iron absorption
      studies, clinical research and field studies. It is concluded that intermittent
      iron supplementation is efficacious and, that in the long term it achieves an
      increase in iron reserves while avoiding sustained oxidative stress caused by
      current practices of excess daily iron supplementation, particularly in the
      developing world. The stage is set for long-term weekly iron supplementation
      programs in large population groups to determine its sustainability and
      effectiveness.

PMID- 10971833
TI  - Iron fortification with special reference to the role of iron EDTA.
AB  - Iron fortification has been used for decades in a number of industrialized
      countries to combat iron deficiency and seems to have played a significant role
      in reducing its prevalence, especially in infants and women. The overall strategy
      has been one in which staples such as wheat, flour, have been fortified with
      iron. While the effects appear to have been positive, there are still problems
      not yet completely resolved. In this context, the selection of the fortificant
      always represents a compromise between a choice of chemically reactive compounds
      of high bioavailability, such as ferrous sulfate, and inert compounds, which are
      poorly absorbed. Ferrous sulfate is very effective when added during the
      preparation of bread and bakery products and infant formulas, but cannot be used
      in stores flour because of organoleptic problems and inert compounds, such as
      elemental iron powders, have to be used. The search, therefore, continues for
      compounds of high bioavailability which do not cause organoleptic changes in the
      vehicles to which they are added. Problems associated with effective iron
      fortification programmes are compounded in a number of developing countries by a
      variety of factors. Most potential vehicles are not centrally processed,
      inhibitory ligands in staple cereal diets depress the absorption of both
      intrinsic and fortification iron, anemia is often of multifactorial in etiology,
      financial resources are scanty and governmental support sometimes lacking.
      Despite such difficulties there are encouraging signs of progress in a number of
      countries, using a variety of fortificants and vehicles. In the present review
      particular attention is paid to the potential role of NaFeEDTA as a fortificant
      in developing countries. It is much less affected by the inhibitors of iron
      absorption present in diets of low bioavailability, it can be added to a number
      of vehicles without causing organoleptic problems and its efficacy has been
      underlined in three intervention studies.

PMID- 10971834
TI  - Iron deficiency and neural development: an update.
AB  - In Latin America, 10-30% of reproductive age females and upwards of 40-70% of
      pregnant women may be iron deficient. The true prevalence in young children and
      infants is often hard to determine because of problems in survey design, data
      collection, or sampling. There is little doubt, however, that iron deficiency
      anemia is a significant nutritional problem in many infants within the first 5
      years of life. Numerous intervention studies have been performed across the world
      with varying success and it is clear that in nearly all situations it is a
      preventable disease with preventable consequences. One such consequence is the
      alteration in cognition that occurs in iron deficient individuals during the
      early parts of their life cycle and perhaps at later times as well. While iron
      deficiency was once presumed to exert most of its deleterious effects only if
      anemia was present, it is now clear that many organs show morphologic,
      physiologic, and biochemical changes before there is any drop in hemoglobin
      concentration. Iron deficiency is associated with alterations in many metabolic
      processes that may impact brain functioning; among them are mitochondria electron
      transport, neurotransmitter synthesis and degradation, protein synthesis,
      organogenesis, and others. It is necessary to separate the developmental aspects
      of iron deficiency and neural functioning from the aspects of iron deficiency
      that could occur at any time in life. A number of reviews have discussed the
      links between brain iron and neuropathology, brain iron, nutrition, and
      development, and iron status and cognition. New knowledge concerning the
      acquisition of iron by the brain in early life is being generated by numerous
      research groups. In the next decade a much clearer understanding of the role of
      brain iron on neural functioning will probably emerge.

PMID- 10971835
TI  - [Role of iron in immunity and its relation with infections].
AB  - Experimental evidence in the last decades show that iron is a fundamental element
      for normal development of the immune system. Its deficiency affects the capacity
      to have an adequate immune response. The role of iron in immunity is necessary
      for immune cells proliferation and maturation, particularly lymphocytes,
      associated with the generation of a specific response to infection. The body has
      the capacity to reduce the iron availability to be consumed by infectious
      elements by proteins such as transferrin and lactoferrin. Also, iron is essential
      for the proliferation of bacteria, parasites, and neoplastic cells. Thus excess
      iron could potentially facilitate the development of infections and the invasion
      of tumoral cells. The immune system has bacteriostatic mechanisms that reduce the
      availability of the metal, interfering with bacterial growth. Additionally the
      system uses iron as the intermediary in the production of bacteriostatic cells.

PMID- 10971836
TI  - [New alternatives in the prevention of iron deficiency. Use of genetic
      engineering in food modification].
AB  - This article reviews the possible applications of new food biotechnology
      techniques to introduce some compounds into plants or animals. The potential for
      these plant modification methods has ample applications ranging from improvements
      in food production and development for human consumption, production of
      antibodies or therapeutic proteins, inclusion of nutrients to improve nutritional
      value of the food to production of vaccines. It must be clear though that
      currently the scope and consequences of such modifications are not completely
      clear. There is some concern about potential secondary effects and the hypothesis
      of the appearance of new viruses due to recombinant genetical transformations
      that have not been totally rejected. However the tendency is towards considering
      the process as safe. Finally some evidence is presented about the possibility of
      introducing the capacity to synthesize vitamin A in vegetables or produce rice
      with high content of iron as real alternatives to fight some of the nutritional
      deficiencies most common worldwide.

PMID- 10971837
TI  - Carotenoids and human health.
AB  - After the discovery of vitamin A in 1913, the yellow pigments of fruits and
      vegetables were soon implicated as compounds with similar nutritional effects.
      beta-Carotene was shown to be converted into vitamin A by Moore in 1929, and the
      chemical structures of both vitamin A and beta-carotene were determined two years
      later. Thus, the sole function of beta-carotene in human health was considered to
      be its conversion into vitamin A. On the basis of observational epidemiologic
      studies, conducted in the mid-1970s, however, carotenoids were implicated as
      protective agents, first against lung cancer and then against a variety of other
      chronic diseases. Intervention trials employing beta-carotene, however, either
      have shown no preventive effect or indeed, in two cases, have enhanced the
      incidence of lung cancer in middle-aged male smokers and asbestos workers. The
      possible protective action of carotenoids can be attributed to their properties
      as singlet oxygen quenchers and as antioxidants, whereas their cancer-enhancing
      actions in lung can be ascribed to the prooxidant action of carotenoid free
      radicals in damaged cells. Apart from chronic diseases, beta-carotene has shown
      significant therapeutic value in individuals suffering from photosensitivity
      disorders and provides temporary relief to persons afflicted with leukoplakia. A
      part from a medical context, the colored carotenoids found in many living
      organisms and in many foods delight both the eye and the palate. Thus, human
      health and the enjoyment of life are greatly benefited by the presence of these
      interesting pigments in nature, whether or not they ultimately prove to have more
      specific protective effects against chronic diseases.

PMID- 10971838
TI  - Lycopene entrapped in human albumin protects 2'-deoxyguanosine against singlet
      oxygen damage.
AB  - The generation of electronically excited molecular oxygen 1O2 has been shown to
      occur in several biological systems, such as photooxidation of a variety of
      biological compounds and xenobiotics ("photodynamic action") and also enzymatic
      reactions. The high reactivity of 1O2 with unsaturated compounds, sulfides and
      amino groups arises from its electrophilicity and relatively long lifetime. Thus,
      biological targets for 1O2 having the above functional groups include unsaturated
      fatty acids, proteins, enzymes and DNA. There is interest in the role of
      nutrition in the prevention and pathogenesis of cancer. Epidemiological studies
      in humans have suggested that carotenoids aid in cancer prevention. Lycopene and
      oxycarotenoids are present at significant levels in cells and plasma. Extensively
      conjugated biomolecules such as carotenoids act largely on physical quenching of
      1O2 and in much lesser extent on chemical reaction. In this study we observed the
      protective effect of beta-carotene and lycopene entrapped in human albumin (HSA)
      against the oxidative 1O2 attack of 2'-deoxyguanosine (dGuo). Photosensitization
      with methylene blue associated with Chelex resine or Polymer-Rose bengal
      (Sensitox) and thermodecomposition of water-soluble endoperoxide 3,3'-(1,4
      naphthylidene)dipropionate were employed to generate 1O2. The detection of 8-oxo
      7,8-dihydro-2'-deoxyguanosine(8-oxodGuo) and 4-hydroxy-8-oxo-7,8-dihydro-2'
      deoxyguanosine(4-OH-8-oxodGuo) were performed using reversed phase HPLC with UV,
      electrochemical detection and by electrospray ionization mass spectrometry.
      Results showed a significant decrease in the amount of 8-oxodGuo in the presence
      of lycopene. The percentages of 4-OH-8-oxodGuo and 8-oxodGuo measured were 50%
      and 70% lower than the control, respectively. These data indicate that
      carotenoids entrapped in albumin can be an efficient quencher of 1O2 and may be
      of interest in protecting against the deleterious effect of this excited state
      molecule.

PMID- 10971839
TI  - Bioavailability of carotenoids.
AB  - Our current knowledge about the bioavailability of provitamin A carotenoids in
      foods is insufficient, fragmentary and difficult to interpret. Past methods of
      estimating the vitamin A value of food carotenoids suffer both from uncertainty
      about the meaning of bioavailability and from the inadequacy of the indicators
      used in its determination. Reported conversion ratios of beta-carotene to vitamin
      A in humans in vivo, depending on conditions, range from 2:1 to 26:1
      (microgram/microgram). Thus, the ratio of 6:1, devised by the World Health
      Organization, must be considered as a rough average estimate that is not
      applicable to all diets. Strategies to increase the dietary intake of carotenoid
      containing foods should include measures to enhance carotenoid bioavailability.

PMID- 10971840
TI  - The role of provitamin A carotenoids in the prevention and control of vitamin A
      deficiency.
AB  - That beta-carotene is the main source of vitamin A in fruits and vegetables has
      been known for many years. Many studies have been conducted to assess
      bioconversion of beta-carotene to vitamin A in animals. More recently,
      bioconversion studies using stable-isotopically labeled beta-carotene have been
      used to assess bioconversion in humans. The efficiency of the bioconversion of
      beta-carotene to vitamin A has been accepted to be six but this value may vary
      depending on vitamin A status and the amount of beta-carotene consumed. This
      paper reviews the human studies on purified beta-carotene supplements and/or
      consumption of fruits and vegetables conducted to ascertain whether beta-carotene
      can alter the vitamin A status of deficient populations. The conclusion is that
      data are lacking from well-designed studies to show that, with the possible
      exception of red palm oil, beta-carotene-rich foods are as effective as vitamin A
      supplements for eliminating vitamin A deficiency. Nevertheless, the data do show
      that beta-carotene-rich foods may be important for preventing vitamin A
      deficiency.

PMID- 10971842
TI  - Changes in carotenoids during processing and storage of foods.
AB  - Being highly unsaturated, carotenoids are susceptible to isomerization and
      oxidation during processing and storage of foods. Isomerization of trans
      carotenoids to cis-carotenoids, promoted by contact with acids, heat treatment
      and exposure to light, diminishes the color and the vitamin A activity of
      carotenoids. The major cause of carotenoid loss, however, is enzymatic and non
      enzymatic oxidation, which depends on the availability of oxygen and the
      carotenoid structure. It is stimulated by light, heat, some metals, enzymes and
      peroxides and is inhibited by antioxidants. Data on percentage losses of
      carotenoids during food processing and storage are somewhat conflicting, but
      carotenoid degradation is known to increase with the destruction of the food
      cellular structure, increase of surface area or porosity, length and severity of
      the processing conditions, storage time and temperature, transmission of light
      and permeability to O2 of the packaging. Contrary to lipid oxidation, for which
      the mechanism is well established, the oxidation of carotenoids is not well
      understood. It involves initially epoxidation, formation of apocarotenoids and
      hydroxylation. Subsequent fragmentations presumably result in a series of
      compounds of low molecular masses. Completely losing its color and biological
      activities, the carotenoids give rise to volatile compounds which contribute to
      the aroma/flavor, desirable in tea and wine and undesirable in dehydrated carrot.
      Processing can also influence the bioavailability of carotenoids, a topic that is
      currently of great interest.

PMID- 10971841
TI  - Enrichment of the diet with synthetic and natural sources of provitamin A.
AB  - The use of available food rich in provitamin A and retinol as well as
      fortification of local food are known to result in adequate vitamin A status. In
      Brazil, several regional foods are known to be good sources of provitamin A such
      as buriti, several palm oils, mango and others. Improving the consumption of
      these locally available natural sources of provitamin and vitamin A would cover
      the needs of the vulnerable population. At the same time fortification of
      industrialized foods with natural and/or synthetic forms of provitamin A could
      speed up and fill the gap between requirement and low intake of this vitamin in
      many parts of the country. This approach has been considered by many as the most
      effective intervention program to prevent micronutrient deficiencies in
      developing countries. Our previous studies on the subject have shown that cooking
      vegetable oil, mainly soybean oil, is a very good alternative vehicle to be
      fortified and supply vitamin A to the population. Lately we have also enriched
      the same soybean oil with beta-carotene. Addition of this provitamin A to the oil
      showed it to be stable when heated at cooking and frying temperatures (retention
      of 92.4 +/- 6.7% and 65.4 +/- 8.6%, respectively). When rat or human food was
      prepared with carotene-enriched cooking oil, its bioavailability in experimental
      animals and absorption in humans were shown to be adequate. An alternative for
      Brazil, besides adding chemical forms of the vitamin to the cooking oil, would be
      to mix available carotene-rich palm oil to the soybean oil. There are already
      regional uses of carotenoid-rich palm oils in the preparation of local dishes in
      some parts of Brazil and this would facilitate its acceptance by the population.
      Enrichment of common foods in Brazil, such as soybean oil, with chemical forms of
      beta-carotene or mixing rich sources of provitamin A can be a good alternative to
      improve the intake of vitamin A by the Brazilian population.

PMID- 10971843
TI  - Processing characteristics and stability of chemically synthesized carotenoids in
      food systems.
AB  - Product development is driven by consumer demand for variety in food. Increasing
      health awareness and a corresponding lifestyle are the main factors that
      influence the development of new food products. The pure nutritional aspect of
      food is becoming less and less important, leaving enjoyment and health as the
      major motivators of consumer preference. Research & Development and Technical
      Service departments for carotenoid formulations have been taking up these
      challenges for a long time. They have developed carotenoid formulations with
      processing characteristics and stability to meet the customer's requirements.
      Carotenoids that are approved under food laws are used as colorants. beta
      carotene is also important as provitamin A and as a physiologically active
      substance. Carotenoid formulations are available as dispersions, powders and
      emulsions. They must meet the requirements of the different food production
      processes. Ease of handling, and stability to light, air and heat are important
      technical features of our carotenoid formulations. Some of the main processing
      parameters and the stability of carotenoid formulations are discussed with
      reference to the beverage industry, margarine production and the dairy industry.

PMID- 10971844
TI  - Chromatographic separation of carotenoids.
AB  - The carotenoids are extremely reactive and consequently unstable due to their
      long system of conjugated double bonds. Several precautions, such as protection
      against light and oxygen, use of low temperature and antioxidants, analysis in
      the shortest possible time, should be taken during isolation and chromatography.
      The food samples, preferably fresh, are homogenized and immediately extracted
      with a suitable organic solvent. Saponification has been employed in order to
      hydrolyze the carotenoid esters, remove fatty material and destroy chlorophyll.
      This optional step facilitates subsequent carotenoid separation, identification
      and quantification. The separation of carotenoids is usually carried out by
      column chromatography, thin layer chromatography and high performance liquid
      chromatography, in analytical or preparative scale, on many stationary phases
      such as silica-gel, alumina, MgO, Ca(OH)2 and reversed-phase material (C18 and
      C30). The choice of the most suitable chromatographic method depends on the
      amount of sample, carotenoid composition, resolution, speed and purity required.
      Examples of carotenoid separation in different stationary phases will be shown
      and discussed.

PMID- 10971845
TI  - Sources of errors in the quantitative analysis of food carotenoids by HPLC.
AB  - Several factors render carotenoid determination inherently difficult. Thus, in
      spite of advances in analytical instrumentation, discrepancies in quantitative
      results on carotenoids can be encountered in the international literature. A good
      part of the errors comes from the pre-chromatographic steps such as: sampling
      scheme that does not yield samples representative of the food lots under
      investigation; sample preparation which does not maintain representativity and
      guarantee homogeneity of the analytical sample; incomplete extraction; physical
      losses of carotenoids during the various steps, especially during partition or
      washing and by adsorption to glass walls of containers; isomerization and
      oxidation of carotenoids during analysis. On the other hand, although currently
      considered the method of choice for carotenoids, high performance liquid
      chromatography (HPLC) is subject to various sources of errors, such as:
      incompatibility of the injection solvent and the mobile phase, resulting in
      distorted or split peaks; erroneous identification; unavailability, impurity and
      instability of carotenoid standards; quantification of highly overlapping peaks;
      low recovery from the HPLC column; errors in the preparation of standard
      solutions and in the calibration procedure; calculation errors. Illustrations of
      the possible errors in the quantification of carotenoids by HPLC are presented.

PMID- 10971846
TI  - [Regulatory aspects in the use of natural colorants].
AB  - A number of preparations of natural colours from vegetable, insect and algae
      sources are presently used in various foods, although many of them have not been
      evaluated in relation to their safety of use. In evaluating the toxicity of food
      additives the concept of the Acceptable Daily Intake (ADI) has been used to
      provide an indication of safety for use and to enable regulatory authorities to
      take adequate legislative measures for their control. This paper will focus on
      the principles for the safety assessment of food additives, with emphasis on the
      guidelines that have been established by the Joint Expert Committee on Food
      Additives and Contaminants (JECFA) for evaluating natural food colours. Recent
      data on the potential intake of annato extracts in Brazil and current aspects of
      regulation of food colours at the level of MERCOSUR will also be presented.

PMID- 10971847
TI  - [Annatto: technological advances and perspectives].
AB  - Colorants derived from the seeds of annatto (Bixa orellana, L.) are extensively
      used in the food industry. Their pecular characteristics, as that which permits
      obtaining water-soluble and lipid-soluble colorants through small alterations of
      the production process, was one of the factors responsible for the success of
      this pigment. It can be observed that only recently, a little over five years,
      efforts have been dedicated to the study of the physico-chemical characteristics
      of the different carotenoid structures that compose the so-called annatto
      colorant. The very industry that produces the colorant has only recently
      perceived the possibility of obtaining colorants of different hues from annatto
      seeds and has dedicated studies to this respect. On the other hand, complementary
      toxicological studies of these pigments are being demanded, putting their
      utilization in question, and only with the conclusion of these work can their
      future be evaluated.

PMID- 10971848
TI  - Latin American food sources of carotenoids.
AB  - Latin America has a wide variety of carotenogenic foods, notable for the
      diversity and high levels of carotenoids. A part of this natural wealth has been
      analyzed. Carrot, red palm oil and some cultivars of squash and pumpkin are
      sources of both beta-carotene and alpha-carotene. beta-carotene is the principal
      carotenoid of the palm fruits buriti, tucuma and bocaiuva, other fruits such as
      loquat, marolo and West Indian cherry, and sweet potato. Buriti also has high
      amounts of alpha-carotene and gamma-carotene. beta-Cryptoxanthin is the major
      carotenoid in caja, nectarine, orange-fleshed papaya, orange, peach, tangerine
      and the tree tomato. Lycopene predominates in tomato, red-fleshed papaya, guava,
      pitanga and watermelon. Pitanga also has substantial amounts of beta
      cryptoxanthin, gamma-carotene and rubixanthin. Zeaxanthin, principal carotenoid
      of corn, is also predominant only in piqui. delta-Carotene is the main carotenoid
      of the peach palm and zeta-carotene of passion fruit. Lutein and beta-carotene,
      in high concentrations, are encountered in the numerous leafy vegetables of the
      region, as well as in other green vegetables and in some varieties of squash and
      pumpkin. Violaxanthin is the principal carotenoid of mango and mamey and is also
      found in appreciable amounts in green vegetables. Quantitative, in some cases
      also qualitative, differences exist among cultivars of the same food. Generally,
      carotenoids are in greater concentrations in the peel than in the pulp, increase
      considerably during ripening and are in higher levels in foods produced in hot
      places. Other Latin America indigenous carotenogenic foods must be investigated
      before they are supplanted by introduced crops, which are often poorer sources of
      carotenoids.

PMID- 10971850
TI  - [LATINFOODS and its role in the generation and compilation of data for Latin
      America].
AB  - LATINFOODS is the Latin American organization, affiliated to INFOODS, involved in
      the generation and compilation of data on the composition of foods, and with the
      methods of analysis and the users of the data. UN and FAO are the organizations
      which have supported the activities of this network, through the realization of
      workshops, specific courses, symposia analyzing present situation and future
      plans of action. One of the concrete actions has been the preliminary edition of
      the Food Composition Table of Latin America (1998). Among the priorities of
      LATINFOODS is the generation of data on various nutrients, among which the
      carotenoid pigments occupy a fundamental place. The original reason for their
      determination and their compulsory inclusion in food composition tables of all
      countries was related directly to their provitamin A activity or retinol
      equivalents as classically expressed in the mentioned tables. In this context,
      beta-carotene, because of its higher biological activity, was preferentially
      determined. It is known that in nature, both in the plant and in the animal
      kingdom, there are numerous carotenoid pigments that play diverse roles, other
      than the classic ability to confer attractive color to foodstuffs, ranging from
      yellow, passing through orange to red. The desire to know the composition of the
      different carotenes and xanthophylls in fresh and processed foods has increased
      in recent years because of their biological activity as antioxidants in vivo in
      humans. This circumstance has given new impulse to the study of carotenoids in
      foods other than beta-carotene. Methods to determine carotenoids constitute
      another priority for LATINFOODS. A course sponsored by FAO has been carried out,
      but the realization of new concrete activities is necessary, given the complexity
      of the subject which requires vast experience and is led in Brazil by Dr. Delia
      Rodriguez-Amaya. It is hoped that the next edition of the Food Composition Table
      for Latin America, which will be published in two years, will have the maximum
      information about these compounds. Our region is privileged with native foods
      which are potentially excellent sources of carotenoids. It is our duty to carry
      out this investigation as soon as possible, considering its importance at all
      levels.

PMID- 10971849
TI  - [Investigation needs on carotenoids in Latin America].
AB  - Many recent papers show the important role of bioactive phytochemicals to
      maintain a good health status. Among them the carotenoids are the best known.
      About 637 have been described and possibly 70 of them could have an important
      role in human health, 16 have been found in human brain in high amounts. Most of
      the studies have found relations between the carotenoids and chronic non
      communicable diseases like several types of cancer, atherogenic disease and some
      degenerative pathology of the eye. This relation is mediated by genes and age.
      Studies of carotenoids are of scientific and economic interest for Latin America
      as many tropical products are high sources of these compounds. Therefore the
      first task is to analyze them and iniciate some evaluation on its metabolic
      availability. A coordinated regional work is proposed, in which 40 or 50 fruits
      and vegetables are analyzed in terms of the seven carotenoids most related to
      human health. At the same time it will be important to start epidemiological
      studies that will compare groups with different levels of consumption of fruits
      and vegetables and make chronic disease risk analysis. In some countries of the
      Latin American region, with the support of FAO and INFOODS, some courses and
      meetings are taking place so that in a short time period the carotenoid
      composition of the important regional foods will be completed and a carotenoid
      regional food composition table be published.

PMID- 10971851
TI  - [Panorama of the investigation on carotenoids in Brasil: perspectives and needs].
AB  - During the last two decades Brazil has produced more than 80 scientific papers on
      carotenoids, most of which dealing with food composition, development of
      analytical methodology and the factors that influence composition. Varietal
      differences, agricultural practices, climate and stage of maturity, as well as
      food storage, processing and preparation are the main influencing factors.
      Studies on bioavailability and the functions and actions in health have also been
      carried out and are expanding. Recently, interest has grown on the degradation of
      carotenoids with the production of either desirable or undesirable aroma/flavor
      in foods. For the future, analytical and compositional studies should continue to
      enlarge the basis for agronomic, nutritional, medical and biotechnological
      projects. It is fundamental that the quality of analytical data continues to
      receive top priority, for this can mean the difference between reliable and
      confounding results, regardless of the sub-area of application.

PMID- 10971852
TI  - [Investigation needs on carotenoids in the republic of Argentina].
AB  - There are no national dietary surveys regarding nutrient intake of Argentine
      population. On the other hand, nutrient content of foods in Argentina, as in
      other Latin American countries, is unknown because there are no data on food
      composition. Therefore, nutrient intakes must be calculated using foreign
      composition tables. In relation to vitamin A nutritional status, high prevalence
      of low vitamin A intake and low plasma retinol levels have been found in the
      eighties in several groups of university students. In this report, results of a 7
      day dietary survey of students attending the course of Nutrition in the
      Universities of Buenos Aires, Lujan and Tucuman are presented. Information was
      processed in a PC Computer (VAN Program, Lujan University, Argentina) to obtain
      the mean daily intake of carotenes with and without provitamin A activity,
      according to the German Food Composition Tables. The results showed that
      provitamin A carotenes provided between 40 and 82% of the vitamin A recommended
      allowances and that about 20% of the population had total carotene intake lower
      than 4 mg/day. These results are in agreement with other dietary surveys carried
      out in students in previous years and are a consequence of some characteristic
      feeding habits of the Argentine population. In order to obtain more reasonable
      results regarding actual intakes in our population, study of the composition of
      national foods would be imperative.

PMID- 10971853
TI  - [Priorities of investigation in the field of carotenoids in Venezuela].
AB  - The Venezuelan Food Composition Table (VFCT) is being revised for the publication
      of the ninth edition within the Venezuelan Food Project. The majority of the RE
      values for plant foods given in the VFCT were taken from previous editions (1964
      1973) and with few exceptions, still remains the same in the latest edition of
      1994. These values were calculated from the total carotenoid content of food,
      determined by an open column method with no separation of the various carotenoids
      that might be present in the food. Recently it has been suggested that the
      accepted factors to convert beta-carotene and other carotenoids to RE (1/6 and
      1/12, respectively) do not reflect the reality and the apparent mean vitamin A
      activity of leafy vegetables and carrot would be around 23% and fruits about 50%
      of that assumed until now. Percentages of the Venezuelan RDAs for vitamin A were
      calculated from vitamin A intake supplied by food consumption surveys, using the
      conversion factors corrected according to the above mentioned criteria.
      Percentages of the Venezuelan RDAs were again calculated with the vitamin A
      availability given by the Food Balance Sheet (1997), using two levels of RE in
      carrots: 2,800 ER and 850 ER. Results in these approaches differ markedly and
      indicate that the vitamin A nutrition status may be overestimated. If confirmed,
      this situation could influence the criteria and decisions in regard to food
      fortification and other strategies for controlling vitamin A deficiency.

PMID- 10971854
TI  - [Importance of blood tests for the diagnosis of drug allergies].
AB  - This work is devoted to the study of 22 dossiers of persons who have presented
      with clinical signs following taking a drug. The study was confined to patients
      in whom the symptoms had as origin a hypersensitivity (true or non-specific by
      histamine release). This study has allowed analysis of the value of several
      serological tests (measurement of leukotrienes, activation of basophils and T
      specific lymphocytes) in diagnosis and so to define the path to take that is best
      adapted to each case. The conclusion presents an agreement between the suspected
      diagnosis, after allergy enquiry and prick-tests, and the results of serological
      tests.

PMID- 10971855
TI  - [Anaphylactoid reaction to goat's milk].
AB  - We report on one young adult male patient who had severe anaphylactoid reaction
      after eating cheese made from goat's milk. This allergy to goat and sheep's milk,
      known by the patient, gave mainly rise to oral pruritus. Cow's milk and cheese
      were always eaten without any incident. Labial test and specific IgE antibodies
      confirm goat and sheep's milk allergy without cow's milk allergy.

PMID- 10971856
TI  - [Pollens and the environment: what does what at the regional and local levels?].
AB  - In order to study the links between pollinoses and pollens in the most efficient
      way, it is essential to understand better who works in towns, in departments or
      in a region, for the development and protection of the environment. Study of the
      links between health and the environment must include all the bodies,
      institutions and partners.

PMID- 10971857
TI  - [Allergy emergencies in children: care at school].
AB  - Half of the life of children is spent in schools. Emergencies may occur, due to
      food anaphylaxis or other allergic causes. Main clinical pictures are
      anaphylactic shock, laryngeal angioedema, acute asthma. Lethality is a risk.
      Recent French rules go into more details about the management of emergency cases
      and the need of training for teachers and other members of the educational staff.
      The need to use injectable i.m. adrenaline is underlined in a protocol with
      consents of parents and agreement of all parties. Eviction diets are not yet
      guaranteed so that parents are allowed to provide their children with suitable
      meals. The authors debate about the indications of such protocols.

PMID- 10971858
TI  - [Importance of air purifiers in the prevention of respiratory allergy].
AB  - Prevention of respiratory allergy and thus diminution of its prevalence consists
      of the application not only of preventative measures on the allergens themselves,
      but also on atmospheric pollutants such as NO, CO and diesel particles. These
      modify the allergens and increase synthesis of allergen-specific IgE. Use of air
      purifiers, on condition that they have HEPA or ULPA filters may contribute to
      reduction of allergenicity linked to pollutants and are one of the not-negligible
      means of protection from respiratory allergy and asthma in particular.

PMID- 10971859
TI  - Preventive symptomatic immunotherapy versus placebo in seasonal rhinitis due to
      grasses in children and to Parietaria in adult patients.
AB  - BACKGROUND: EPD is the only preventive symptomatic immunotherapy available on the
      market and approved by competent bodies. Recent double-blind placebo controlled
      (DBPC) studies have demonstrated its efficacy in seasonal and perennial rhinitis.
      The aim of the study was to confirm the efficacy and safety of a single dose of
      immunotherapy administered six-eight weeks before the pollen season. METHODS: Two
      simultaneous DBPC trials were carried out. The first consisted of 20 children
      with grass-pollen seasonal rhinitis (Bollate-Milano, Italy) and the second
      included 30 adult patients with Parietaria-pollen seasonal rhinitis (Genova,
      Italy). EPD was administered only to the active groups. RESULTS: A significant
      difference in favour of the active treatment groups was seen in oral
      antihistamine use (p < 0.05) during the peak pollen seasons. Throughout the
      pollen seasons, rhinoconjunctivitis scores for the two groups in both studies
      presented no significant difference, even if the values were lower in the active
      groups. CONCLUSIONS: The oral antihistamine reduction, observed in the active
      groups during the seasonal period, supports the efficacy of this treatment,
      although a significant improvement in the rhinoconjunctivitis symptoms was not
      observed, probably due to the use of oral antihistamine in the placebo groups.
      The overall profile of the EPD was good. It could be particularly suited for
      short term therapy to prevent seasonal symptoms in allergic patients.

PMID- 10971860
TI  - Hepatitis C virus kinetics.
AB  - The balance of virus production and clearance for untreated patients with chronic
      hepatitis C virus (HCV) results in a decline of viraemia when initiating active
      antiviral treatment. During the first phase of interferon-alpha therapy, after a
      delay of about 8-9 h, the kinetics of the viral load is characterized by a rapid
      dose-dependent decline. This early response can be observed for almost all
      patients treated with interferon-alpha. After about 24-48 h, the viral decline
      enters a second phase of relatively slow exponential decay during the following
      weeks of therapy. Non-responding patients, however, show constant viraemia or
      even a rebound during this second phase. The rate of the exponential decline of
      the viral load in responding patients in this second phase is less sensitive to
      the dose of interferon-alpha and varies considerably among patients. Furthermore,
      combination therapy with interferon-alpha plus ribavirin does not significantly
      improve the initial viral decay, although it may prevent more patients from
      rebounding. Mathematical modelling of viral dynamics reveals high turnover rates
      of pre-treatment viral production and clearance, and permits the estimation of in
      vivo half-lives of a few hours for free HCV virions and of 1-70 days for
      productively infected cells. Infected cell death rate, which determines the
      second phase decline slope, is predictive of response to treatment. Current
      models indicate that the early biphasic viral decline is explained if interferon
      alpha partially blocks virion production from infected cells, yet they do not
      rule out additional antiviral or immunological effects. Therapeutic implications
      are the advisability of use of frequent (daily) and comparatively high initial
      doses. In conclusion, kinetic analysis of the viral decay during the first weeks
      of treatment permits the prediction of response at the end-of-therapy and might
      help to evaluate new drugs and to optimize therapy.

PMID- 10971861
TI  - Intensification of background antiretroviral therapy with abacavir during low
      level failure may restore optimal suppression.
AB  - OBJECTIVE: To investigate the antiviral activity of abacavir added to stable
      background therapy. DESIGN: Retrospective analysis. MATERIALS AND METHODS: In 27
      subjects with detectable plasma viraemia during stable treatment abacavir was
      added as the only agent. Patients were pre-treated for 180 weeks (mean) with
      regimens containing zidovudine (102 weeks) and lamivudine (88 weeks). Results
      were analysed in two groups: group 1, > 400 HIV RNA copies/ml; group 2, 25-399
      copies/ml. In 7/13 group 1 patients genotypic resistance analysis was performed
      prior to abacavir. RESULTS: Median follow-up was 28 weeks, median HIV RNA load at
      baseline 2.48 log10 copies/ml (3.52 and 1.66 log10 copies/ml in groups 1 and 2,
      respectively). Plasma viraemia was reduced to less than 400 HIV RNA copies/ml in
      2/13 subjects in group 1 and 11/11 in group 2 (week 24). Only one patient in
      group 1 responded transiently to less than 25 HIV RNA copies/ml. In contrast,
      10/14 and 11/11 in group 2 reached values below this threshold at weeks 12 and
      24, respectively. Overall, 7/13 group 1 patients were found with > or = 2
      zidovudine resistance-associated mutations. The lamivudine resistance-associated
      mutation M184V was present in four of seven cases. All of these patients showed
      only a moderate and transient reduction of plasma viraemia (medium peak reduction
      of 0.73 log10 after 20 weeks). CONCLUSIONS: The addition of abacavir during low
      level treatment failure may restore or achieve suppression to levels below the
      cut-off of the ultrasensitive PCR.

PMID- 10971862
TI  - Enhanced antiviral benefit of combination therapy with lamivudine and alpha
      interferon against WHV replication in chronic carrier woodchucks.
AB  - Cell culture studies in our laboratory previously demonstrated synergistic
      antiviral activity for the combinations of lamivudine and a novel recombinant
      hybrid human alpha B/D interferon (rHu alpha B/D IFN) against hepatitis B virus
      (HBV) replication. Based on these results, a study was designed to determine if
      an enhanced antiviral effect with this drug combination could be demonstrated in
      vivo using the woodchuck hepatitis virus (WHV)/woodchuck experimental model of
      chronic HBV infection. Both antiviral agents have been shown to be effective
      against WHV replication in WHV chronic carriers during previous studies by our
      laboratories. Two combination treatment regimens were compared to matched
      monotherapies in a placebo-controlled trial. The first used simultaneous
      administration of rHu alpha B/D IFN and lamivudine for 24 weeks. The other
      combination treatment regimen used a staggered dosing schedule of 12 weeks of
      administration of lamivudine alone, followed by 12 weeks of simultaneous dosing
      with both drugs, followed by 12 weeks of therapy with rHu alpha B/D IFN alone.
      Both treatment regimens with combinations of lamivudine and rHu alpha B/D IFN
      were more effective at reducing WHV replication in chronically infected wood
      chucks than the corresponding monotherapies. Both combination treatments produced
      antiviral effects that were at least equal to that expected for additive activity
      based on estimations generated by Bliss Independence calculations. The staggered
      treatment regimen reduced viraemia and intrahepatic WHV replication significantly
      more than that expected for additive interactions, indicating synergistic
      antiviral effects. These studies demonstrate that combination therapy of chronic
      WHV infection has enhanced antiviral benefit over corresponding monotherapies and
      indicate that combination treatment of chronic HBV infection can be superior to
      therapies using a single antiviral agent.

PMID- 10971863
TI  - Virological failure among patients on HAART from across Europe: results from the
      EuroSIDA study.
AB  - OBJECTIVES: To monitor the response to highly active antiretroviral therapy
      (HAART) over time and the proportions of patients with poor virological control
      in order to help provide some insight into drug resistance. DESIGN: Analysis of
      data from the EuroSIDA study; an observational study initiated in 1994 of almost
      8500 patients with HIV from across Europe. METHODS: Patients who initiated HAART,
      and had both a CD4 lymphocyte count and viral load measured in the 3 months prior
      to starting HAART, were included in analyses. The proportion of patients with a
      poor virological response (defined as a viral load of > 10,000 copies/ml, using
      either a single measure or two consecutive measures) at 16 and 48 weeks was
      determined. Multivariate logistical regression was used to determine the factors
      associated with a poor virological response at both time points. RESULTS: Median
      CD4 cell count at starting HAART was 218 cells/mm3 [interquartile range (IQR),
      113-327 cells/mm3] and median viral load was 4.36 log10 copies/ml (IQR, 3.57-5.04
      log10 copies/ml). At 16 weeks, 16% had a viral load of > 10,000 copies/ml based
      on a single viral load measure and 10% if the more stringent definition of two
      consecutive viral loads above this level was used. At 48 weeks these proportions
      were 19% and 13%, respectively. Compared with patients from Southern Europe,
      patients from both Central and Northern Europe had approximately half the chance
      of a poor virological response at 16 weeks (odds ratios 0.53 and 0.47, P = 0.0015
      and P < 0.0001, respectively), while at 48 weeks both regions still had
      approximately a 25% reduced chance of a poor virological response, but this was
      no longer statistically significant (odds ratio 0.77 and 0.75, P = 0.17 and P =
      0.13, respectively). CONCLUSIONS: There were marked difference in virological
      response to HAART across regions of Europe, which may be partly explained by
      regional differences in access to HAART and utilisation. If drug resistance is
      closely related to virological failure, these results may help to provide an
      early insight into the potential problem of drug resistance across Europe.
      Continued follow-up is essential to monitor patients with poor virological
      control.

PMID- 10971864
TI  - HIV-1 drug resistance testing: health outcomes issues.

PMID- 10971866
TI  - [Differential diagnosis of B-cell lymphoma rich in T cells and peripheral T-cell
      lymphomas].
AB  - Clinicomorphological analysis of T-cell-rich B-cell lymphoma in a 50-year-old
      female and literature data revealed objective difficulties in morphological
      diagnosis using cytological and histological methods. Large number of epithelioid
      histiocytes and tumor cells polymorphism resembled Lennert's lymphoma (peripheral
      T-cell lymphoma). Immunohistochemical study confirmed B-cell origin of tumor
      cells and large number of reactive T-cells. It is suggested that it would be more
      correctly to use the term "Lennert-like areas" in such cases with subsequent
      immunohistochemical study.

PMID- 10971865
TI  - [Dipeptidyl aminopeptidase-IV as a histochemical marker of differential diagnosis
      of large cell anaplastic CD30+-lymphoma and Hodgkin's disease].
AB  - Using histochemical methods, we studied distribution of dipeptidylaminopeptidase
      IV (DPP-IV) in tumor cells of 16 patients with non-Hodgkin's malignant lymphomas
      (NHL) including B-cell NHL (10 cases), pleomorphic T-cell lymphoma (1 case),
      CD30+ anaplastic large cell lymphoma (ALCL) of T-cell (1 case) and ALCL of null
      cell type (4 cases) and of 13 patients with Hodgkin's disease (HD). The results
      indicate that tumour cells of pleomorphic T-cell NHL and ALCL of T- and null-cell
      type showed DPP-IV activity. In contrast, no DPP-IV activity was seen in the
      tumor cells of B-cell NHL (lymphocytic, centroblastic/centrocytic, centroblastic,
      immunoblastic), in Berezovsky-Reed-Sternberg and Hodgkin's cells of different HD
      variants. These results demonstrate that difference in DPP-IV activity between
      tumor cells of ALCL and HD may be diagnostically important for separation of ALCL
      from HD and moreover may be used in verification of the borderline between HD
      like ALCL and ALCL-like HD. It is possible that DPP-IV activity contributes to
      pathogenesis of ALCL and may determine clinical behaviour of this NHL being
      involved in autocrine and paracrine regulation of tumor cell growth of ALCL.

PMID- 10971867
TI  - [Differential diagnosis of hepatocellular carcinoma using laser DNA
      cytofluorometry].
AB  - Because of insufficient amount of material obtained in many cases of puncture
      biopsy, Differential diagnosis of hepatocellular carcinoma (HCC) with benign
      tumors and focal cirrhotic lesions of the liver is difficult. The study was aimed
      at development of additional criteria for HCC differential diagnosis of the basis
      of a comparison of morphological data (histological and cytological) with DNA
      content in the cells of focal lesion of the liver and is based on the research of
      biopsy material from 111 patients with focal liver lesions. Laser DNA flow
      cytometry (DNA-FCM) was carried out in 59 samples using laser flowing cytometer
      FACScan (Becton Dickinson, USA). The complex of three HCC histological criteria
      was established (trabecular histoarchitecture, increased nuclear-cytoplasmatic
      rate and nuclear crowding) for comparison with puncture biopsy of the liver
      (diagnostic efficiency 93.7%). Optimal quantitative parameters for HCC diagnosis
      were the following: reduction of the number of cells in a GO/1 phase of the cell
      cycle (< 77.5%), appearance of aneuploid clone of cell DNA index > 1.0 and
      decreased percent of binucleated cells (< 10%). Very high diagnostic specificity
      of the research was found (98.3%). Usage of quantitative parameters in the
      complex with histological criteria of HCC increased efficiency of the diagnosis
      up to 98%.

PMID- 10971868
TI  - [Cytological differential diagnosis of different variants of peripheral lung
      tumors].
AB  - Cytological differential diagnostic features of bronchiolo-alveolar carcinoma and
      papillary adenocarcinoma are established basing on the material of needle
      biopsies by means of Statistica program. It is found that the strongest influence
      on the cytological diagnosis of these two tumors is associated with the following
      pairs of cytological features: lane--clear-cut cell borders and lane--the
      presence of macrovacuoles.

PMID- 10971869
TI  - [Morpho-ecological characteristics of thyroid diseases in various regions of
      Russia and Belorussia from surgical data].
AB  - Thyroid lesions were histologically studied on surgical material obtained in 1992
      1996 in 12 regions of Russian Federation and Republic of Belarus. Various forms
      of thyroid pathology were considered with reference to local ecological
      situation. An increase of thyroid carcinoma incidence and particularly that of
      papillary carcinoma was observed in regions with radiation pollution (Chelyabinsk
      and Bryansk regions). A high degree of correlation exists between the incidence
      of various forms of thyroid pathology and radiation situation. This is also true
      for pollution of sewage and the presence of ferrous metallurgy factories. No
      correlation was found with the pollution of atmosphere.

PMID- 10971871
TI  - [Comparative morphological characteristics of bronchial mucosa in patients with
      chronic obstructive bronchitis and bronchial asthma].
AB  - The material for histoultrastructural study was biopsies obtained by
      fibrobronchoscopy from 12 patients with endogenic bronchial asthma (BA) and 4
      patients with chronic obstructive bronchitis (COB). The principal periods of
      affection in these diseases, the role of bronchial epithelium, effector cells of
      inflammation, nervous elements, smooth muscle cells, microcirculatory
      disturbances in patho- and morphogenesis of chronic obstructive pulmonary lesions
      are determined. The results indicate that BA develops due to disturbances of
      adaptive mechanisms being in some cases the issue of COB progression.

PMID- 10971870
TI  - [Morphological changes in male sexual glands in Kaluga regions contaminated with
      radionuclides].
AB  - 41 testes of males who died after living 7-9 years in Kaluga region contaminated
      with radionuclides after the Chernobyl accident (1-5 and higher Ci/km2) were
      studied morphologically. Various alterations were found in 75.6% of the cases.
      All the testes contained Cs-137 (11-45 Bq/kg). The correlation between the
      radionuclide content and level of radiation pollution was lacking. Maximal
      content of Cs-137 was in testicular tissue of boys (45 Bq/kg).

PMID- 10971872
TI  - [Morphology of the cerebral cortex in fetuses and extremely low weight newborns
      in normal pregnancy and miscarriage of hormonal etiology].
AB  - Complex histologic, histostereometric and electron microscopic study of fields 4
      and 6 of the brain cortex in fetuses and newborns with an extremely low body
      weight allowed to specify formation of histoarchitectonics of the motor analyser
      during the second trimester of perinatal ontogenesis. Stages of differentiation
      (20-23 weeks) and maturation (24-27 weeks) of neurons and cytoarchitectonic
      layers of the motor zone in uncomplicated pregnancy as well as slow maturation of
      this cortex region in incomplete pregnancy of hormonal genesis were discovered.
      In this condition, there are lengthening of the neuron differentiation stage up
      to 26 weeks of gestation and important reduction of histostereometrical values
      (thickness of individual cytoarchitectonic layers and that of all the cortex) and
      cytokaryometrical values (volume of neuron nuclei) as compared to those in
      uncomplicated pregnancy.

PMID- 10971873
TI  - [Pathomorphology of organs of late spontaneously miscarried fetuses in ascending
      infection of placenta].
AB  - Organs and placentas in 262 late spontaneous miscarriages caused by ascending
      bacterial infection of the fetal balloon were studied. The most important were
      the data on the stages of intrauterine pneumonia development and its link with
      the stages of infection in the fetal tissues and periods of pregnancy. The
      information is provided on the direct causes of fetal death related to structural
      functional insufficiency of fetal membranes, placenta and umbilical cord.

PMID- 10971874
TI  - [A method of preparing sections for express histological diagnosis].
AB  - The method of improving quality of histological slides for intrasurgical
      diagnosis is proposed. The method consists in preliminary microwave processing of
      the slice of surgical material before putting in into cryostat for freezing and
      sections preparation. A slice of surgical material was first immersed in 10 ml of
      physiological solution (pH = 7.2). Then it was exposed to microwave radiation
      (2.45 GHz, 1 W/cm2) for 1.5 min. After that the slice was put into cryostat and
      frozen. Microwave processing is done in a home microwave oven or working chamber
      of microwave histoprocessor. Essential advantage in quality of slides is
      obtained.

PMID- 10971875
TI  - [Endovascular papillary angioendothelioma].
AB  - One case of a rare vascular tumor which occurs mainly in the childhood is
      presented. The tumor has a tendency to recurrence and metastases into the
      regional lymph nodes in spite of a relatively mature structure.

PMID- 10971876
TI  - [Cryoglobulinemic vasculitis].
AB  - A postmortem case of cryoglobulinemic vasculitis is reported. A 67-year-old male
      had hemorrhagic component, affection of the kidneys, skin, lungs and
      gastrointestinal organs. The disease began in 1994 with extreme weakness,
      headache, fever, skin eruption. Antibodies to B and C hepatitis were found. The
      condition of the patient worsened since 1997 when renal deficiency reached the
      degree of uremia. Before the autopsy the diagnosis was: chronic
      glomerulonephritis with cryoglobulinemia in context of systemic vasculitis with
      involvement of the skin, gastrointestinal tract, fever syndrome.
      Pathomorphologically, the patient had proliferative vasculitis with leukoclasia
      in the skin, chronic mesangiocapillary glomerulonephritis in the kidney,
      fibrosing alveolitis and vasculitis with affection of small vessels in the lung,
      chronic hepatitis in the liver. The anatomopathological diagnosis was as follows:
      cryoglobulinemic vasculitis of the hemorrhagic vasculitis type with involvement
      of the kidneys, skin, gastrointestinal tract and the lungs. Differential
      diagnosis with other microscopic vascilitides: main distinctions of
      cryoglobulinemic vasculitis are immune deposits consisting of cryoglobulins in
      the wall of small vessels. The most frequent components of cryoglobulins are IgM
      and IgG. These are main morphological, classifying and differential-diagnostic
      signs.

PMID- 10971877
TI  - [Development of regional pathoanatomical service].

PMID- 10971878
TI  - [Morphology and pathology of the appendix and their clinical significance].
AB  - High content of the lymphoid tissue in the appendix confirms the immunoreceptor
      function of this organ as the most probable. It consists in regulation of food
      enzyme disintegration by means of feedback evaluation of the chyme antigenicity.
      The degree of this function disturbance determines damage to the appendix:
      functional, non-destructive, destructive. Therefore, differential approach is
      necessary in the treatment allowing to preserve this organ in many cases.

PMID- 10971879
TI  - Factors that influence personal perceptions of the risk of an acute myocardial
      infarction.
AB  - Personal risk perceptions of acute myocardial infarction (AMI) affect people's
      preventive health behaviors as well as their beliefs during a heart attack
      episode. The authors investigated factors that are associated with personal risk
      perceptions of having an AMI. A random-digit-dial survey was conducted among 1294
      respondents, aged 18 years or older, in 20 communities across the nation as part
      of the Rapid Early Action for Coronary Treatment (REACT) trial. Results of two
      mixed-model linear regression analyses suggested that worse perceived general
      health, more risk factors, and greater knowledge were associated with greater
      perception of AMI risk. The results also showed that women who answered,
      incorrectly, that heart disease is not the most common cause of death for women
      in the United States reported significantly lower risk perceptions than women who
      answered this question correctly. The findings in this study suggest that
      interventions need to target specific misconceptions regarding AMI risk.

PMID- 10971880
TI  - An organizational climate intervention associated with increased handwashing and
      decreased nosocomial infections.
AB  - Handwashing practices are persistently suboptimal among healthcare professionals
      and are also stubbornly resistant to change. The purpose of this quasi
      experimental intervention trial was to assess the impact of an intervention to
      change organizational culture on frequency of staff handwashing (as measured by
      counting devices inserted into soap dispensers on four critical care units) and
      nosocomial infections associated with methicillin-resistant Staphylococcus aureus
      (MRSA) and vancomycin-resistant enterococci (VRE). All staff in one of two
      hospitals in the mid-Atlantic region received an intervention with multiple
      components designed to change organizational culture; the second hospital served
      as a comparison. Over a period of 8 months, 860,567 soap dispensings were
      recorded, with significant improvements in the study hospital after 6 months of
      follow-up. Rates of MRSA were not significantly different between the two
      hospitals, but rates of VRE were significantly reduced in the intervention
      hospital during implementation.

PMID- 10971881
TI  - Psychological and physical health effects of sexual assaults and nonsexual
      traumas among male and female United States Army soldiers.
AB  - Lifetime trauma history was assessed in a health study of active duty United
      States Army soldiers. Five hundred fifty-five male and 573 female soldiers in the
      sample were asked whether they had ever experienced 14 different potentially
      traumatic experiences, including sexual assaults, violent stressors to self, and
      terrifying events that occurred to others and were secondarily traumatic through
      exposure by gaining information or as a witness to the event. Most soldiers had
      experienced multiple traumas, and premilitary exposure to events was much more
      common than exposure to events after entering the military. Global measures of
      current psychological distress and physical health symptoms were predicted by the
      lifetime number of sexual assaults and traumas to self. Social support from
      military unit leaders moderated the relationship between accumulated exposure to
      traumas and both health measures, whereas unit cohesion was directly associated
      with fewer mental health problems.

PMID- 10971883
TI  - Gender and euthanasia.

PMID- 10971884
TI  - Are human genes patentable?

PMID- 10971882
TI  - Improvements in chronic diseases with a comprehensive natural medicine approach:
      a review and case series.
AB  - Approximately 40% of the US population report using complementary and alternative
      medicine, including Maharishi Vedic Medicine (MVM), a traditional, comprehensive
      system of natural medicine, for relief from chronic and other disorders. Although
      many reports suggest health benefits from individual MVM techniques, reports on
      integrated holistic approaches are rare. This case series, designed to
      investigate the effectiveness of an integrated, multimodality MVM program in an
      ideal clinical setting, describes the outcomes in four patients: one with
      sarcoidosis; one with Parkinson's disease; a third with renal hypertension; and a
      fourth with diabetes/essential hypertension/anxiety disorder. Standard symptom
      reports and objective markers of disease were evaluated before, during, and after
      the treatment period. Results suggested substantial improvements as indicated by
      reductions in major signs, symptoms, and use of conventional medications in the
      four patients during the 3-week in-residence treatment phase and continuing
      through the home follow-up program.

PMID- 10971885
TI  - Health care and the presidential election.

PMID- 10971886
TI  - Illness as failure. Blaming patients.

PMID- 10971887
TI  - The principles of the Belmont report revisited. How have respect for persons,
      beneficence, and justice been applied to clinical medicine?

PMID- 10971888
TI  - Ignore the law.

PMID- 10971889
TI  - The best-laid plans.

PMID- 10971890
TI  - Can a physician always be compassionate?

PMID- 10971891
TI  - The 18th of October 1999. In memoriam. The story of a Cuban-American family and
      some lessons for patient care.

PMID- 10971892
TI  - Phase I cancer trials. A collusion of misunderstanding.

PMID- 10971893
TI  - A code of ethics for the health Internet.

PMID- 10971894
TI  - Recruiting subjects for clinical trials: strategies and perils.

PMID- 10971895
TI  - On the Hippocratic sources of Western medical practice.

PMID- 10971896
TI  - Medicine is a humane art. The basic principles of professional ethics in Chinese
      medicine.

PMID- 10971897
TI  - The efficacy of professional ethics. The AMA code of ethics in historical and
      current perspective.

PMID- 10971898
TI  - The role of medical associations in developing professional values.

PMID- 10971899
TI  - Professional values in modern clinical practice.

PMID- 10971900
TI  - How professional values are developed and applied in medical practice in China.

PMID- 10971901
TI  - The development of professional character in medical students.

PMID- 10971902
TI  - Ethics teaching in medical schools.

PMID- 10971903
TI  - A caring and teaching organization. The ethical lessons of the hospital.

PMID- 10971904
TI  - On the development of teachers of medical ethics in China.

PMID- 10971905
TI  - Ethical values in the education of biomedical researchers.

PMID- 10971906
TI  - Interactional styles of bullies and victims observed in a competitive and a
      cooperative setting.
AB  - Observational data were used to examine the interactional styles of bullies and
      victims while they participated in 2 different games: 1 cooperative and 1
      competitive. Participants included 17 bullies, 18 victims, and 35 controls (all
      aged 8-11 years) selected through a peer nomination questionnaire. Bullies and
      victims were observed 4 times in total: twice during the cooperative game and
      twice during the competitive game, each time paired with a partner of opposite
      status or control status. Results indicated that when bullies and victims
      interacted together, bullies showed a dominant style in the dyad, often
      regulating and opposing victims' initiatives. Victims, on the other hand,
      complied with bullies' requests and presented a submissive style of interaction.
      However, interactions involving control partners indicated that (a) bullies
      opposed those partners' initiatives less frequently and (b) victims tended to
      affirm themselves by asking for help and explanations. These data provide
      evidence for an interactional model in explaining the dynamics between bullies
      and victims.

PMID- 10971907
TI  - Predictors of college students' alcohol consumption: implications for student
      education.
AB  - Understanding why young adults consume alcohol the way they do can lead to more
      effective educational programming for promotion of students' personal health and
      safety. The authors examined the predictive role of expectations about alcohol,
      perceived peer norms of consumption, awareness of rules, and individual self
      efficacy in conjunction with demographic variables for male and female college
      students' weekly alcohol consumption. The sample of 4,960 students analyzed here
      is 10 to 20 times larger and more nationally representative than the samples used
      in similar studies. The authors used a general linear model; 41% of the men's
      variance and 33% of the women's variance in self-reported weekly alcohol
      consumption were explained by the set of predictors. In descending order of
      variance accounted for in male and female students' self-reported weekly alcohol
      consumption, perceived gender-specific norms of consumption, expectations about
      the effects of alcohol, and the importance of drinking in high school were
      significant predictors for both men and women. The salience of psychological
      variables for young adults' consumption of alcohol underscores the importance of
      recognizing individual predictors of behavior in the broader ecological context
      in which those behaviors are performed.

PMID- 10971908
TI  - The influence of maternal child-rearing attitudes and teaching behaviors on
      preschoolers' delay of gratification.
AB  - This study was an exploratory examination of the influence of mothers' teaching
      behaviors, strategies, and child-rearing attitudes on their children's ability to
      delay gratification. In an externally imposed delay of gratification situation,
      30 mothers from a rural university community taught their children strategies
      that could help them refrain from touching a brightly wrapped present when the
      mothers left the room. Results showed that mothers of children who did not delay
      gratification exhibited teaching behaviors and child-rearing attitudes consistent
      with a permissive parenting style, whereas mothers of children who did delay
      gratification exhibited teaching behaviors and child-rearing attitudes consistent
      with an authoritative parenting style. The results of this study are discussed
      with respect to the development of children's self-control and self-regulatory
      abilities.

PMID- 10971909
TI  - Effects of mothers' locus of control for child improvement in a developmentally
      delayed sample.
AB  - A potentially important variable that has received little attention in the
      literature is the locus of control (LOC) a caregiver holds for child improvement,
      including its influence on the caregiver's treatment compliance and on actual
      child improvement. In this study, 131 mother-child dyads were assessed across 1
      year, to evaluate the utility of the LOC construct in a practice setting.
      Children were approximately 4 years old at the first assessment, and all of them
      had been diagnosed with a developmental disability. Mothers' compliance with
      treatment (mothers' attendance at sessions; teachers' ratings of mothers' support
      and knowledge) was tracked, and measures of child development status and mothers'
      locus of control were administered. Statistical results indicated that mothers'
      locus of control was not significantly correlated with children's gains in
      development over the year. The mothers' beliefs about whether the child or chance
      would be responsible for improvement were associated with lower compliance with
      treatment, whereas the mothers' beliefs that child improvement was attributable
      to professional intervention were associated with enhanced involvement in
      treatment.

PMID- 10971910
TI  - The effect of a nonverbal aid on preschoolers' recall for color.
AB  - The purpose of the present study was to investigate whether the provision of a
      nonverbal memory aid would improve preschoolers' recall of color. Forty 4-year
      old children carried out 2 tasks with the same set of colored objects. Colors
      were not referred to, nor were children told that their recall would later be
      tested. One day later, the children were split into 2 groups. One group was given
      a chart containing both the colors of the objects and distractor colors. The
      other group was not given a chart. Recall for object color was tested. There was
      an effect of chart provision; children who used the chart recalled more colors
      correctly than did those who did not use a chart. This result indicates (a) that
      even very young children can make use of props to facilitate their recall and (b)
      that such memory aids need not be exact copies of previously seen objects.
      Implications of these findings for eyewitness recall are discussed.

PMID- 10971911
TI  - Phenomenology of bibliotherapy in modifying teacher punitiveness.
AB  - The authors examined the phenomenology of bibliotherapy and its effects in
      changing preservice teachers' punitive attitudes toward children. Participants (N
      = 29) were enrolled in a university course (Introduction to Emotional
      Disturbance). Five books by Torey Hayden, autobiographical accounts of teaching
      and building relationships with students with emotional and behavioral disorders,
      were read and discussed within the framework of group bibliotherapy. Participants
      completed a self-report rating form measuring their tendency toward punitiveness
      during the first and last weeks of the 15-week semester. Participants also
      completed a questionnaire measuring the bibliotherapeutic impact of reading
      Hayden's texts, and they kept journals about the experience of reading Hayden.
      Comparison of the group's pre- and post-measures on punitiveness showed a small,
      albeit significant decrease in punitiveness; decreased punitiveness was
      associated with the therapeutic impact of reading Hayden. Phenomenological
      analysis of the participants' journal entries revealed that the structure of the
      experience of reading Hayden was one of identification with the protagonist,
      leading to emotional and cognitive learning.

PMID- 10971912
TI  - Secular declines in Spearman's g: some evidence from the United States.
AB  - The Flynn Effect (J. Flynn, 1987) refers to the apparent increases in
      intelligence quotient (IQ) observed over the past few decades. A related
      phenomenon is that the variance in test scores accounted for by Spearman's g (C.
      Spearman, 1904) varies according to IQ level. That is, g accounts for less
      variance in high IQ groups than in low IQ groups. Spearman termed this variant
      aspect of g the "law of diminishing returns." This study extends prior research
      on the Flynn Effect and the law of diminishing returns by examining changes in
      the statistical importance of Spearman's g that may accompany secular increases
      in IQ. Based on the standardization data from the United States versions of the
      Wechsler scales (i.e., Wechsler Preschool and Primary Scales of Intelligence, D.
      Wechsler, 1967; Wechsler Intelligence Scale for Children, D. Wechsler, 1949;
      Wechsler Adult Intelligence Scale, D. Wechsler, 1955), this study indicated that,
      in most cases, the statistical significance of Spearman's g has indeed declined
      over the past several years. A. R. Jensen (1998) suggested that the components of
      the Flynn Effect warrant special investigation. The present study addresses this
      issue, in part by analyzing the Verbal and Performance subscales of the Wechsler
      scales. Additionally, this study further confirms the law of diminishing returns
      as applicable to different ages and time periods.

PMID- 10971913
TI  - Facial morphology and children's categorization of facial expressions of
      emotions: a comparison between Asian and Caucasian faces.
AB  - The effects of Asian and Caucasian facial morphology were examined by having
      Canadian children categorize pictures of facial expressions of basic emotions.
      The pictures were selected from the Japanese and Caucasian Facial Expressions of
      Emotion set developed by D. Matsumoto and P. Ekman (1989). Sixty children between
      the ages of 5 and 10 years were presented with short stories and an array of
      facial expressions, and were asked to point to the expression that best depicted
      the specific emotion experienced by the characters. The results indicated that
      expressions of fear and surprise were better categorized from Asian faces,
      whereas expressions of disgust were better categorized from Caucasian faces.
      These differences originated in some specific confusions between expressions.

PMID- 10971914
TI  - Syntactic processing of Hebrew sentences in normal and dyslexic readers:
      electrophysiological evidence.
AB  - The authors examined differences in brain activity as measured by amplitudes and
      latencies of event-related potential (ERP) components in Hebrew-speaking adult
      dyslexic and normal readers. The participants were measured while processing
      words' syntactic functions during reading of sentences with subject-verb-object
      syntactic order. The results suggested that among dyslexic and normal readers,
      N100 and P300 ERP components were sensitive to certain constituents of syntactic
      analysis for target words in accordance with their grammatical roles. The
      findings further demonstrated significant differences in ERP measures between
      dyslexic and normal readers. Compared with normal readers, dyslexic readers
      exhibited consistently higher amplitudes and longer latencies in both ERP
      components for the subject of the sentence. Significant, though less consistent,
      ERP variations were observed for other sentence elements. In addition, dyslexic
      readers differed from normal readers in their processing strategies. For normal
      readers, the verb-oriented, morphologically based strategy was found to be the
      most efficient for sentence processing in Hebrew, whereas the dyslexic readers
      demonstrated a more primitive mode of identification of words' grammatical roles,
      namely, the word-order strategy. The results support the hypothesis that there is
      a syntactic processing "weakness" in dyslexics.

PMID- 10971915
TI  - Perceptions of children who lie: influence of lie motive and benefit.

PMID- 10971916
TI  - Building the ethics of nursing inquiry as we build the science.

PMID- 10971917
TI  - Pediatric short bowel syndrome: pathophysiology, nursing care, and management
      issues.
AB  - ISSUES AND PURPOSE: A comprehensive overview of the etiology, pathophysiology,
      nursing care, and medical and surgical management of the child with short bowel
      syndrome (SBS), which follows massive anatomical or functional loss of the small
      intestine. CONCLUSIONS: The outlook for children with SBS has improved due to
      recent advances in parenteral and enteral nutrition, pharmacologic interventions,
      and surgical options. PRACTICE IMPLICATIONS: Nurses whose practice reflects an in
      depth knowledge of the etiology, pathophysiology, medical and surgical
      management, nursing interventions, and complications of SBS will be equipped to
      provide quality care for children and families affected by SBS.

PMID- 10971918
TI  - Low-income mothers' perceptions of health in their children with growth delay.
AB  - ISSUES AND PURPOSE: Parental characteristics are the strongest predictor of poor
      health for children. This study examined how low-income mothers of children with
      growth delay define health for their children, and the behaviors they use to
      monitor their children's health. DESIGN AND METHODS: Naturalistic design using
      Kleinman's Explanatory Model approach and interviews with 22 mothers. RESULTS:
      Mothers consider nutritious food as a primary contributor to their children's
      health and consider healthy children to be chubby. Other indicators of health
      include children's energy levels, provision of nutritious food, and physical and
      mental activity balanced with rest. PRACTICE IMPLICATIONS: A mother's explanatory
      model of health for her child can guide health promotion targeted to the mother's
      beliefs.

PMID- 10971919
TI  - Without parental consent: conducting research with homeless adolescents.
AB  - ISSUES AND PURPOSE: To identify the ethical and legal implications of conducting
      research with homeless adolescents and to discuss guidelines for conducting
      research without parental consent. CONCLUSIONS: Ethical principles of capacity,
      risk, postponement, and truthful disclosure within the context of the rights of
      minors to consent to healthcare treatment form the basis of the argument for
      allowing adolescents to consent to participate in research without parental
      consent when there is minimal risk or when such consent could place them at
      increased risk for harm. PRACTICE IMPLICATIONS: Adolescents who are the target
      population for clinical research or who are intended recipients of nursing care
      should be involved in setting priorities, purposes, and protocols. Parents and
      other adults from their communities should be included in developing strategies
      to protect their confidentiality and privacy while helping them achieve autonomy
      in making informed health-related decisions.

PMID- 10971920
TI  - Talking with teens: successfully screening for high-risk behavior.

PMID- 10971921
TI  - Linking practice with research: the role of the unit research coordinator.

PMID- 10971922
TI  - Pediatric nursing comes full circle.

PMID- 10971923
TI  - [Accidents and their health effects in firemen of rescue and firefighting teams].
AB  - Accidents, traumas and poisoning are the most frequent causes of health
      impairments among firemen, determined by the nature of their occupation. Their
      work is directly related with the exposure to various harmful chemical and
      physical factors, involving at the same time mental stress during rescue and
      firefighting actions. The aim of the analysis performed was to determine the
      accident rate, range and causes of accident-related absenteeism among firemen of
      the rescue and firefighting brigades, as well as to indicate major traumas
      resulting from accidents at work. The study was carried out in a group of 1503
      firemen (7% of the total number of firemen in Poland) employed in the rescue and
      firefighting brigades, selected at random throughout the country. Workers'
      personal data, as well as the data on the number of accidents and the number of
      days of work disability during the years 1994-97 were analysed. Accidents and
      accident-related absenteeism by age, certified causes and sites (body parts) of
      traumas were also analysed using the following parameters: the accident rate (the
      number of accidents per 1000 workers), accident severity rate (the number of work
      disability days per one accident), and absenteeism rate (the number of accident
      related work disability days per 100 employed). In the period under study (1994
      97) 352 accidents, involving 301 persons were registered. Thus, the accident rate
      was 70.3. These accidents were responsible for the period of work disability
      three times higher (293.5 days/100 workers) than that observed in the male
      population employed in the national economy, and eight times higher (770.2
      days/100 workers) in the 50-59 age group. Dislocations and distortions were the
      most frequent causes of accident-related absenteeism--48, whereas fractures
      occupied the second place--25%. Burns were classified among the most severe
      injuries, resulting in more than 90 days of absenteeism annually, but they made
      only 7% of absenteeism with frequency rate of 2.2/1000. Legs, ankles and feet
      were the most frequent sites of injuries (60% of accidents with 170.2 days of
      absenteeism per 100 workers) which may be of significance in preventing hazards
      occurring in this occupational group.

PMID- 10971924
TI  - [Evaluation of patient exposure to X-ray in view of monitoring carried out in
      diagnostic laboratories of Lodz region].
AB  - X-ray diagnostics, mostly due to a large variety of examinations, and a wide
      range of its application, is the major source of exposure to ionising radiation
      in the population. That is why special measurements are being carried out to
      evaluate the air-kerma values received by patients during X-ray examinations
      performed most frequently (i.e. lumbo-sacral spine radiography, chest
      radiography, and thoracic spine radiography). The measurements were performed in
      39 different departments (in the Lodz region). The doses received by patients
      were measured simultaneously using thermoluminescence dosimetry (TLD) and a CONY
      dosimeter (PTW, Frieburg). In all, 196 measurements were made. The results
      obtained were compared with the reference levels recommended by the International
      Agency of Atomic Energy. The study indicates that over 90% of doses received by
      patients during chest radiography exceeds the recommended level. Of the 39 X-ray
      departments under control, in 31 the reference levels were exceeded for at least
      two radiological examinations, which means that in only 20% of departments the
      radiological equipment and work methodology ensure the acceptable levels of
      patients' exposure, while the other departments need interventions to explain the
      reasons why patients receive too high radiation doses, and to eliminate harmful
      over-exposure.

PMID- 10971925
TI  - [Serum selectin E level in lead-exposed workers].
AB  - Lead is recognised as a potential atherogenic factor. One of the earliest events
      in the development of atherosclerosis is monicyte attachment to the endothelial
      surface. This is followed by recruitment of monocytes into the subendothelial
      space and ingestion of modified LDL by these cells. In turn, modified LDL
      stimulates endothelial cells to induce expression of proinflammatory adhesion
      molecules, such as selectins, which further promote monocyte migration. It was
      observed that atherosclerotic vascular damage is associated with increased level
      of circulating selectin E. The aim of this study was to determine the impact of
      the occupational exposure to lead on the serum selectin E level. The study
      involved 80 patients, including 37 workers of a copper foundry and 43 people not
      exposed to lead. The subjects were matched in pairs according to sex, age and
      cholesterol concentration in blood. There were 25 hipercholesterolemic pairs and
      9 pairs with normal serum total cholesterol. People exposed to lead had higher
      (about 7 ng/ml) serum selectin E concentration than those not exposed. There was
      positive linear correlation between selectin E and triglycerides in the whole
      group (p < 0.01), and the strongest correlation was observed in the group of
      subjects not exposed to lead (aged 40-60, r = 0.74). In the context of the
      described hypertriglyceridemic action induced by lead, these results suggest that
      lead could potentially act as an atherogenic factor in the early, inflammatory
      stage of atherosclerosis.

PMID- 10971926
TI  - [Assessment of the hearing system in workers chronically exposed to carbon
      disulfide and noise].
AB  - Epidemiological studies carried out in the years 1984-1993 revealed carbon
      disulfide (CS2) to be one of the major chemical occupational hazards. Whereas
      among physical factors, noise was found to be the most common threat. Industrial
      workers very often face a combined exposure of two or more factors, like CS2 and
      noise, responsible for significant biological risk to the human health, although
      health effects of such an exposure have not as yet been thoroughly recognized and
      explored. The aim of this study was to assess changes in the hearing system in
      people exposed to toxic effect of CS2, recognized as characteristic of an overall
      clinical history of chronic poisoning by this solvent, in cases of concomitant
      exposure to noise exceeding maximum allowable levels. The study covered 80
      workers aged 44-65 years (mean = 44.9 +/- 5.1), employed in a spinning mill of
      viscose fibre for 20.3 years on average (+/- 5.4 years) with clinically observed
      chronic CS2 poisoning, and a group of 40 people (mean age = 56.8 years) exposed
      to CS2 but without subjective or objective symptoms indicating chronic poisoning
      by the solvent. Both groups of subjects at similar age and with almost the same
      duration of employment were exposed to CS2 in concentrations changing in time
      between 10 and 35 mg/m3 (mean concentration = 25.8 mg/m3), and to continuous
      noise with the level ranging from 88 to 92 dB(A) for six hrs per one shift. The
      control group was composed of 40 workers (mean age = 52.0 +/- 5.3 years) employed
      in the cotton industry plant, without contact with CS2 or other chemicals and
      working in the acoustic environment with similar level of exposure to noise (86
      93 dB(A)). Audiological and electronystagmographic examinations revealed
      bilateral retrocochlear hearing impairment associated with symptoms of the
      central vestibular syndrome in 97.5 subjects with diagnosed chronic CS2
      poisoning. In workers free from clinical symptoms of chronic CS2 poisoning,
      perceptive hearing impairment of various degrees was found, including
      retrocochlear in 45% of subjects and cochlear in 32.5%, while in 22.5% of those
      under study normal hearing was observed. In the control group of subjects exposed
      to noise without contact with CS2, sensorineural cochlear hearing loss, typical
      of chronic acoustic trauma without concomitant vestibular disorders, was
      revealed. The results of the study show that in subjects with diagnosed chronic
      CS2 poisoning and exposed to noise, hearing impairment and vestibular disorders
      occur in the form of central changes which suggests a dominating CS2 toxic effect
      on the hearing system. But in some people exposed to both CS2 and noise, the
      hearing impairment in localised in cochlea like in acoustic trauma damage. This
      probably depends on individual susceptibility to harmful effect of these factors.

PMID- 10971927
TI  - [Effects of carbon soot on health of workers involved in the production process
      (1999). Comparison of our own results with those obtained by foreign authors].
AB  - The authors presents similarities and differences in the exposure and health
      condition of workers employed in the Polish plant 'CARBOCHEM' and those working
      in the carbon black industry throughout the world, and discusses publications on
      this subject. Carbon black and smoking are pathogenic factors affecting health of
      people exposed to this substance. Based on the analysis of the foreign literature
      it may be stated that general conclusions are similar, whereas some differences
      are noticed in the results of epidemiological studies. Regardless of these
      differences, there is a need for continuous monitoring of workers' health
      condition, as well as for improving working conditions in which they are
      employed.

PMID- 10971929
TI  - [Cellular radio systems. Problems faced in assessing exposure to electromagnetic
      fields].
AB  - Over twenty years of its existence, cellular radio systems have become one of the
      major sources of human exposure to electromagnetic field (EMF) of high frequency.
      With the increasing number of cellular phones, the interest in health effects of
      exposure to EMF emitted by them continues to grow. At present, there is a general
      opinion that thermal effect (change of electromagnetic energy into thermal
      energy) is an essential mechanism of possible biological effects. The majority of
      world standards for exposure to EMF are based on this effect. The author presents
      Polish standards and those of the International Commission on Nonionizing
      Radiation Protection (ICNIRP) for EMF of frequencies used in cellular radio
      systems, both basic that limits SAR (Specific Absorption Rate), and derived that
      limits the power density, as well as intensity of electric and magnetic fields.
      Attention was also turned to the problems concerning the application of cellular
      phones and those resulting from the character of the field emitted by them to
      which their users are exposed. Bearing in mind the results of the laboratory
      analyses of SAR values occurring in the user's head, and measurements of power
      density in the vicinity of the base station antennas, it can be stated that, in
      view of binding and recommended standards, cellular phones do not present any
      hazard to their users (private or professional). However, it should be stressed
      that standards adopted protect the user's head against the thermal effect,
      whereas the question on whether they also protect against non-thermal effects
      still remains without answer.

PMID- 10971928
TI  - [Causes of occupational allergy in dental nurses. An analysis based on the
      material collected at The Institute of Occupational Medicine in Lodz].
AB  - The causes of occupational dermatosis were analysed in 27 dental nurses examined
      at The Nofer Institute of Occupational Medicine during the years 1995-99. Contact
      sensitisation (at least one positive epidermal test) was found in 18 subjects
      (66.7%). Occupational allergic dermatitis was induced most frequently by:
      glutaraldehyde (7 positive patch tests), nickel (7), benzalkonium (4),
      formaldehyde (4), fragrances (4), chromium compounds (3), glyoxal (3), and
      thiuram (3). In the authors' opinion, dental nurses are nowadays sensitised to
      other chemical compounds than it used to be in the past. The present components
      of disinfectants (aldehydes, quaternary ammonium bases), metals and rubber are
      the major etiologic agents that induce occupational allergy.

PMID- 10971930
TI  - [Hazardous health effects in communal waste collection and disposal workers].
AB  - This paper presents a review of the current literature concerning health impact
      of communal waste in people occupationally involved in waste collection and
      disposal. No studies have been as yet carried out in this regard. This review
      indicates that the main hazards for workers collecting and disposing communal
      wastes comprise organic dust with adsorbed micro-organisms, endotoxins, and
      numerous organic and inorganic chemicals. The major health effects associated
      with the job performed include injuries caused by work-related accidents and
      diseases. Among the most frequent diseases there are allergic and other diseases
      of the respiratory system, as well as musculo-skeletal, gastro-intestinal and
      infectious diseases. Complex hygiene assessment and control of work conditions
      are difficult due to the lack of hygiene standards for micro-organisms and
      endotoxins in the air of the workplace. No studies have been carried out thus far
      in Poland regarding exposure and health effects in workers collecting and
      disposing communal wastes. According to the information available, this problem
      concerns several thousands employees.

PMID- 10971931
TI  - [Exposure assessment strategies for determination of compliance with ceiling
      occupational exposure limits].
AB  - The goal of the assessment of exposure to chemicals is to demonstrate the
      compliance with occupational exposure limit (OEL). There are numerous
      publications on recommended air sampling strategies for compliance measurements
      of time weighted average (TWA) concentrations of chemicals but no clear and
      unambiguous guidelines for measurements and interpretation of ceiling
      concentrations can be found. Furthermore, definitions and interpretation of
      ceiling values in different countries may differ considerably. Systems of
      establishing ceiling limit values, their definitions and interpretation in
      Germany, the USA (OSHA, ACGIH and NIOSH), the UK and Poland have been reviewed.
      In most countries of the European Union and in the USA, continuous monitoring
      using either self contained instruments, multipoint sampling systems or
      multiplexed sensors is considered as being the most appropriate approach. Based
      on the literature review the following air sampling strategies have been
      proposed:--for substances with both OEL--Ceiling and OEL-TWA values dual
      sampling: 8-hour samples for time weighted average concentrations, and in
      parallel short (5-10 min) samples during the expected highest exposure for
      ceiling concentrations measurements; for substances with OEL--Ceiling as the only
      exposure limit (which is preferable); continuous monitoring using direct reading
      instruments, possibly with an alarm device. If such instruments are not
      available, short time measurements may be performed at regular (30 min) intervals
      using direct reading gas analysers or detector tubes.

PMID- 10971932
TI  - [Hearing protectors in prevention of occupational hearing loss].
AB  - The paper presents basic information concerning hearing protectors. The use
      hearing protectors is simplest and most common way of reducing the effect of
      noise on hearing. Design concepts and performance of ear-muffs and ear-plugs are
      presented. The requirements of acoustical and mechanical properties of hearing
      protectors according to European standards adopted in Poland are discussed. The
      values of the main acoustical and mechanical parameters of 97 certified for the
      safety mark hearing protectors are presented. Assumptions for choosing the most
      suitable protectors for a noise spectrum and the principles of their use are
      discussed.

PMID- 10971934
TI  - Helicobacter pylori: an emerging infectious disease.
AB  - Helicobacter pylori is the most common chronic bacterial infection in the world,
      colonizing the stomachs of more than 50% of the human population. The discovery
      of this bacterium has changed the concept of care and management for peptic ulcer
      disease, mucosa-associated lymphomas, gastritis, and gastric carcinoma. Although
      the mode of transmission is not definitively known, person-to-person contact is
      suspected. This article discusses H. pylori, the associated clinical syndromes
      and diseases, risk factors, and current pharmacologic management.

PMID- 10971933
TI  - Physical activity and exercise counseling in primary care.
AB  - Despite the known health benefits of regular physical activity and exercise,
      physical inactivity is prevalent among American adults. The primary care provider
      is in an optimal position to provide physical activity and exercise counseling.
      The Physician-based Assessment and Counseling for Exercise (PACE) program, which
      utilizes the stages of change theory, provides a valuable framework for exercise
      counseling. This article discusses exercise counseling theories and research and
      provides an overview of the PACE program, including the PACE protocols and the
      model's utility in primary care.

PMID- 10971935
TI  - Diagnosing and managing seasonal affective disorder.
AB  - Mood and behavior changes that have a seasonal pattern were first called seasonal
      affective disorder (SAD) in 1984. SAD, which affects about 5% of Americans, is
      most common among reproductive-age women. Afflicted patients typically experience
      debilitating somatic complaints of fatigue, discomfort, lethargy and atypical
      depressive complaints of hypersomnia, increased appetite, carbohydrate craving,
      and weight gain. This article presents current issues in the clinical assessment
      and management of SAD.

PMID- 10971936
TI  - Hallucinations in the vision-impaired elderly: the Charles Bonnet syndrome.

PMID- 10971937
TI  - The public image of nurse practitioners.

PMID- 10971938
TI  - Keeping an open mind after the initial assessment.

PMID- 10971939
TI  - [Results and role of carotid endarterectomy].
AB  - BACKGROUND: The indications for carotid endarterectomy have been defined on the
      basis of several large prospective randomised trials. Today this operation is
      widely performed as primary and secondary stroke prevention in patients with high
      grade carotid artery stenosis. Permanent quality control of the surgical results
      is mandatory to ensure optimal stroke prevention and further reduce perioperative
      complications. METHODS: In this retrospective study we analyse the surgical
      results of 272 consecutive carotid endarterectomies performed in 260 patients
      with special emphasis on the prevention of intraoperative brain ischaemia.
      Patients were operated on in general anaesthesia and moderate hypothermia. Before
      clamping the arteries at the neck, a fast-acting barbiturate or propofol was
      administered intravenously to obtain burst suppression on the EEG. Transcranial
      Doppler sonography allowed continuous intraoperative monitoring of brain
      perfusion and detection of emboli. Intraoperative shunting was performed only
      when the collateral circulation was insufficient. RESULTS: The postoperative
      course was uneventful in 249 endarterectomies (91.5%). The internal carotid
      artery was sonographically recanalised at hospital discharge and at 6-week follow
      up in all 249 cases. Ischaemic cerebral complications were observed in 7 patients
      (2.6%): minor reversible brain ischaemia in 4 (1.5%), and major brain ischaemia
      with infarction in 3 (1.1%). Three patients died in the perioperative period,
      representing a mortality rate of 1.1% in this series. The overall combined stroke
      and death rate was 3.7%. The combined major stroke and death rate was 2.2%.
      Various non cerebral complications occurred in 13 patients (4.8%). CONCLUSIONS:
      These results confirm that endarterectomy is a safe and efficient treatment for
      atherosclerotic carotid stenosis at the neck. Very low complication rates can be
      attained by non-invasive diagnostic methods combined with intraoperative
      monitoring of cerebral blood flow velocity. New upcoming endovascular therapies
      such as percutaneous angioplasty and stenting need to be compared with these
      current surgical results with regard not only to perioperative morbidity and
      mortality but also patency rate, restenosis, and intracerebral blood flow
      restoration.

PMID- 10971940
TI  - [Hereditary hearing loss due to mutations in the connexin-26 gene].
AB  - Hearing loss is a frequent disease with an estimated incidence of 1:1000 in
      children. Hereditary hearing loss is characterised by enormous genetic
      heterogeneity, which makes diagnosis difficult. Approximately 50% of the
      Caucasian patients with autosomal recessive inherited hearing loss carry
      mutations in the connexin-26 gene on chromosome 13. Standard screening procedures
      such as SSCP (single strand conformation polymorphism) analysis, DHPLC
      (denaturing high performance liquid chromatography) and subsequent sequencing are
      used to investigate this gene. A genetic test is thus available which can be
      offered to probands in genetic counselling. We investigated 11 patients with
      hearing loss and found sequence aberrations in 7 patients, which is causative for
      the hearing loss in at least 5 patients. The first application of DHPLC in
      Switzerland is also documented.

PMID- 10971941
TI  - [Sulfasalazine-induced pulmonary infiltrates and Legionella pneumonia].
AB  - After 2 weeks' treatment with sulfasalazine (SASP) and mesalazine enema, a 32
      year-old female with recently diagnosed ulcerative colitis developed bilateral
      pulmonary infiltrates with peripheral eosinophilia. Both drugs were discontinued.
      In view of a high-positive antibody titre (1:4096) against Legionella pneumophila
      serogroups 1-5, legionnaires' disease was assumed and empirical antilegionella
      therapy with macrolid antibiotic was started. The patient's condition improved
      within days. Three months later SASP was given again in view of exacerbation of
      the inflammatory bowel disease. Three days after initiation of therapy acute
      pulmonary symptoms again developed with bilateral, confluent opacities and blood
      eosinophilia. The abnormalities resolved completely after the drug was
      discontinued and prophylactic antibiotic therapy was given. Peripheral lung
      infiltrates with blood eosinophilia are a rare side effect of SASP therapy. The
      prognosis of the illness after the drug has been discontinued is generally good,
      usually with complete recovery of pulmonary function. The risk factors for
      sulfasalazine pulmonary toxicity are not well known. We describe the first case
      of SASP-induced hypersensitivity lung disease with simultaneous Legionella
      pneumophila infection.

PMID- 10971942
TI  - [Toxin treatment of sweat pearls. A review of the treatment of hyperhidrosis with
      a special view of a new therapy option using botulinum toxin A].
AB  - Hyperhidrosis is defined as an excess of sweating beyond the amount needed to
      cool down elevated body temperature. We distinguish a primary and a secondary
      form, where an underlying endocrinological or neurological disease is found. The
      innervation of eccrine sweat glands is sympathetic but the transmitter is
      cholinergic (ACh). There are variable modalities in the treatment of focal
      hyperhidrosis, such as topical aluminium chloride application, tapwater
      iontophoresis, anticholinergic drugs or surgery (axillary sweat gland extraction,
      liposuction or thoracoscopic sympathectomy). Only recently botulinum toxin (BTX)
      has been introduced as a therapeutic tool for hyperhidrosis. As BTX inhibits the
      release of ACh at the cholinergic synapse, perspiration is arrested completely
      after intradermal injection. BTX is a very potent alternative to the surgical
      approach in the treatment of hyperhidrosis, though the treatment must be repeated
      regularly to maintain the effect.

PMID- 10971943
TI  - [Diagnostic problems due to alternative medicine].

PMID- 10971944
TI  - [Realization of the concept of state policy of healthy nutrition in Russia:
      scientific bases].

PMID- 10971945
TI  - [Data on health status for development of food policy].

PMID- 10971946
TI  - [HACCP: internal versus regulatory assessment].

PMID- 10971947
TI  - [One of approaches to the development of nutrition recommendations based on food
      products and using existing databases].

PMID- 10971948
TI  - [Promotion of life-long healthy eating: nutrition education].

PMID- 10971949
TI  - [Physical activity, physical fitness and health (current concepts)].

PMID- 10971950
TI  - [The Codex Alimentarius: a scientific basis for consumer protection and trading
      in food products].

PMID- 10971951
TI  - [Combination toxicology and interactions of additives].

PMID- 10971952
TI  - [Food products, nutrition and health in the Russian Federation].

PMID- 10971953
TI  - [Micronutrients: nutritional aspects and chronic disease].

PMID- 10971954
TI  - [Development of toxicological test methods: possibilities and limitations].

PMID- 10971955
TI  - [Benefits and risks of intakes above the recommended daily dose of
      micronutrients: folic acid and selenium].

PMID- 10971956
TI  - [Relationship between health and protein, carbohydrate and fat consumption].

PMID- 10971957
TI  - [Novel and newly emerging viral infections].
AB  - Methodological approaches to studies of emerging-reemerging anthropogenic and
      natural infections are discussed. Mechanisms of emergence of such situations are
      shown for viruses with high genome changeability (pandemic influenza viruses,
      hepatitis C virus, arboviruses).

PMID- 10971958
TI  - [Laboratory diagnosis of human herpes virus infection].
AB  - Reviews modern data on laboratory diagnosis (virological, immunobiochemical,
      molecular biological methods) and differential diagnosis of herpesvirus infection
      induced by various Herpesviridae.

PMID- 10971959
TI  - [PCR diagnosis of sequences of a novel human herpes virus type 8 in patients with
      Kaposi sarcoma in Russia].
AB  - Associations of a new human herpesvirus type 8 (HHV-8) with different forms of
      Kaposi's sarcoma (KS) in Russia have been studied. Search for this virus genetic
      information has been carried out in biopsy specimens of benign and malignant
      tumors other than KS, and probable sites of HHV-8 latency in human body have been
      checked. HHV-8 sequences were detected by polymerase chain reaction (PCR). HHV-8
      sequences were most often detected in idiopathic (80.6%), AIDS-associated (80%),
      and immunosuppressive (100%) KS. The results indicate a selective association of
      HHV-8 with KS. No probable sites of the virus latency were detected in peripheral
      blood cells of patients with KS and in the prostate of patients with chronic
      prostatitis. The only exception was the husband of a patient with KS: HHV-8
      sequences were detected in his prostatic secretion by nested PCR.

PMID- 10971960
TI  - [Epidemiological and genetical characteristics of first forty cases of HIV
      infection in Perm region].
AB  - The paper sums up molecular epidemiological data on all variants of human
      immunodeficiency virus type 1 (HIV-1) isolated in the Perm region in August 1988
      March 1998. A total of 24 foci (40 cases) of HIV infection were detected; 20 of
      these were imported from other regions (Russian Federation, Ukraine, Belarus,
      Bulgaria, Poland, Uzbekistan, Yugoslavia). In August 1988-September 1996 viruses
      of 3 env subtypes (B, D, and G) were isolated in the region, and the virus was
      mainly sexually transmitted. All cases of HIV infection recorded in September
      1996-March 1998 were detected in intravenous drug users and subjects who had
      sexual intercourse with HIV-infected drug users. The same 3 variants of HIV-1
      with genotypes gagAenvA, gagBenvB, and gagAenvB were isolated in the Perm region
      during this period as in other regions of Russia.

PMID- 10971962
TI  - [New data on the development of complications during epidemiological parotitis in
      children].
AB  - The main factors in the pathogenesis of complicated parotitis virus infection are
      increased virus reproduction in the salivary gland, inhibited by the production
      of alpha-interferon at early stages of the infectious process. Entry of the virus
      into the CNS is caused by slight penetration of antiparotitis antibodies through
      the blood-brain barrier and by poor formation of specific immune complexes at the
      site of primary virus reproduction and in the liquor. Interferon therapy of
      patients with parotitis virus infection corrects the chain of processes in the
      pathogenesis. In parotitic meningitis neovir stimulates gamma-interferon, which
      blocks the synthesis of parotitis antigen in the cell and stimulates (through
      antibody stimulation) the formation of specific immune complexes released with
      the saliva in the gland. Viferon is more active in parotitic orchitis due to
      prolongation of alpha-interferon activity.

PMID- 10971961
TI  - [Characteristics of epidemiological strains of influenza A virus (H3N2) isolate
      in 1997-1999. Virus A/Moscow/10/99--a candidate to become the vaccine strain].
AB  - Antigenic properties of influenza A(H3N2) viruses isolated during two epidemic
      seasons 1997-98 and 1998-99 in Russia are analyzed. All strains are antigenic
      variants of the reference strain A/Sydney/5/97. Characteristics of epidemic
      strain A/Moscow/10/99, proposed by WHO expert committee as vaccine strain for
      1999-2000 have been studied. This strain, isolated on chick embryos, is
      characterized by high reproductive activity in chicken embryos with an infectious
      titer of 10(6) EID50/0.2 ml, easily adapts to MDCK culture, and has a
      thermostable hemagglutinin.

PMID- 10971963
TI  - [Experimental tick-borne encephalitis in golden hamsters treated with specific
      immunotherapy].
AB  - Efficiency of various protocols of specific immunoglobulin treatment was
      evaluated in golden hamsters inoculated with two Far Eastern tick-borne
      encephalitis (TBE) strains. After a low therapeutic dose (0.1 ml) of
      immunoglobulin, corresponding to total dose (60 ml) per course, all parameters
      (survival, immunogenicity, pathomorphology of the brain) deteriorated in animals
      infected with both strains. A higher dose (0.2 ml) corresponding to total dose of
      120 ml notably improved all the studied parameters. The efficiency of specific
      immunoglobulin depends on the clinical and pathogenetic characteristics of TBE,
      determined by the properties of TBE strains. The results validate therapy and
      prevention of TBE by high-titer immunoglobulin in adequate total dose, monitored
      by blood analyses for TBE antigen and evaluations of the time course of IgM
      antibodies.

PMID- 10971964
TI  - [Outbreak of hemorrhagic fever with kidney syndrome in Egor'ev district of Moscow
      region].
AB  - Epizootological, serological, and molecular virological analysis of an outbreak
      of hemorrhagic fever with renal syndrome (HFRS) in the Egoryevsk district of
      Moscow region (September 1995-January 1996) has been carried out. Hantavirus
      (Puumala) antigen and virus-specific antibodies were isolated from bank voles
      captured in the endemic focus. Anti-Puumala antibodies were detected in the sera
      of all HFRS patients and in 2% healthy residents of the endemic focus. Analysis
      of nucleotide sequence (RNA from hantavirus-positive lung of a bank vole) showed
      that the studied hantavirus is a distinct genotype of Puumala virus. Hence, a new
      highly active natural focus of HFRS associated with Puumala virus, dangerous for
      the population, has been revealed in Moscow region.

PMID- 10971965
TI  - [Use of PCR for detection of positive (genomic) and negative (replicative) RNA
      chains of hepatitis C virus in the serum, lymphocytes, and liver of patients with
      chronic hepatitis C].
AB  - The presence of viral RNA in liver tissue and peripheral blood serum and
      lymphocytes of patients with chronic hepatitis C (CHC) was studied by polymerase
      chain reaction with nested primers on the 5'-untranslated region of hepatitis C
      virus (HCV) genome. Positive (genome) RNA was more often detected in the liver
      (81% cases) than in the peripheral blood serum (55%) or lymphocytes (64%). Active
      replication of HCV (presence of negative RNA chains) was observed only in the
      liver (in 37% cases). Correlation between the frequency of HCV RNA detection in
      the liver, blood cells and sera and parameters of the inflammatory process
      activity (SGPT level, histologic activity index and sclerosis index) was
      investigated. No relationship between the studied parameters was revealed.
      Positive correlation between the presence of HCV genome RNA in lymphocytes and
      serum was detected. A tendency to a decrease in the incidence of replicative RNA
      of the virus in liver tissue with increase in the activity of chronic hepatitis C
      was observed.

PMID- 10971966
TI  - [Construction of reference panel of immune serum against hepatitis C virus with
      standard level of IgG antibodies].
AB  - A panel of anti-HCV sera (lot 03HC) was prepared from human sera obtained at
      blood transfusion centers and infectious hospitals. Donor sera and high-titer
      sera from patients infected with HCV were used. For positive samples, specific
      sera reactive with the core and/or NS proteins of HCV 1b and 2 were selected.
      Positive sera were standardized by the concentrations of IgG with a pool of
      negative sera containing no HBsAg and antibodies to HIV, HCV, and syphilis. The
      sera for the panel were selected and titered in screening and specific tests. The
      anti-HCV panel includes negative and positive sera with low and high titers. The
      panel sera are stabilized and can be stored for a short time at room temperature.
      The anti-HCV panel of sera, lot 02HC, was certified at L. A. Tarasevich Institute
      for Standardization and Control as anti-HCV reference panel intended for
      sensitivity, specificity, and stability control of diagnostic systems for
      detection of antibodies to HCV in Russia.

PMID- 10971967
TI  - [Erectile dysfunction--present possibilities of treatment].
AB  - Paper brings the basic information in pathophysiology, diagnostics and
      differential diagnostics in causes of the erectile dysfunction and provides an
      overview of the contemporary therapeutic possibilities, including the new
      substance--sildenafil citrate (VIAGRA). It is stressed that sufficient knowledge
      and responsibility in the indication of therapy may highly support positive
      contribution of the erectile dysfunction and differentiate patients of the
      potential risk. At present, adequate form of treatment of erectile and sexual
      dysfunction exists for almost every patient. New remedies have broaden
      possibilities of treatment, however, they have not done the indication or therapy
      easier.

PMID- 10971968
TI  - [Multiple myeloma--clinical symptoms, diagnosis, prognosis, therapy].
AB  - The triad of clinical features describes multiple myeloma: the accumulation of
      malignant plasma cell in the bone marrow, paraprotein production and bone
      involvement. Moreover, number of characteristic and frequently specific
      complications may develop during the course of disease. Identification of new
      prognostic factors may be helpful for the choice of therapy. The prognosis of
      patients has improved since the introduction of new therapeutic approaches,
      however, multiple myeloma is still mostly fatal malignancy. The clinical and
      laboratory characteristic of myeloma and differential diagnosis of disease are
      described. The results of contemporary therapy and future therapeutic approaches
      are also discussed.

PMID- 10971969
TI  - [Comparison of nutrient intake and corresponding biochemical parameters in
      adolescent vegetarians and non-vegetarians].
AB  - BACKGROUND: In comparison to food habits of non-vegetarians alternative nutrition
      bears several risks, but it also has beneficial effects. Considering risks
      represent a significant age aspect. Nutritional risk and protective factors were
      evaluated in a adolescent group. METHODS AND RESULTS: Food habits of 53
      lactoovovegetarians (mean duration of vegetarianism 3.2 y) assessed by analysis
      of dietary questionnaires were compared to those of 55 nonvegetarians and
      evaluated with respect to basic biochemical indicators (iron, hemoglobin,
      calcium, total protein, cholesterol, fatty acids, vitamin A, beta-carotene,
      vitamin C, vitamin 3). Vegetarians consume less fat, and they have higher intake
      of plant fat, which is reflected din more favourable lipid levels, i.e. lower
      risk parameters of atherosclerosis (cholesterol, LDL-cholesterol, atherogenic
      index, saturated fatty acids) and higher values of factors with antisclerotic
      effect (32.9% ratio of HDL-cholesterol vs. 30.6% in non-vegetarians,
      polyunsaturated fatty acids, vitamin E/cholesterol ratio, vitamin C). Total
      plasma protein levels are balanced in both groups (intake of full value mixture
      of amino acids from grains, legumes (soya), and mild in vegetarians, similar
      intake of total proteins with a small difference in plant protein consumption).
      Iron and calcium absorption is inhibited in vegetarians as a consequence of
      presence of plant food--physic acid, oxaloacetic acid (20.7% hyposiderinemia vs.
      0% in non-vegetarians, high iron intake in both groups, iron from plant sources
      represented 82% in vegetarian boys and 95% in vegetarian girls, hypocalcemia in
      28% of vegetarians vs. 7.3% of non-vegetarians). Vegetarians have significantly
      higher levels of all antioxidant vitamins. This is result of higher consumption
      of vegetables, fruit, plant fat and sprouts. Higher intake and higher levels of
      antioxidants are reflected in significantly lower lipoperoxidation values.
      CONCLUSIONS: Lactoovovegetarian nutrition represents risk for adolescents if the
      values of iron and calcium are considered, however it has positive aspects on
      lipid parameters, protein values, and antioxidant parameters.

PMID- 10971970
TI  - [Relation of serum levels of the soluble cytoadhesion molecules sVCAM-1 and sICAM
      1 to selected factors in the cytokine network in multiple myeloma].
AB  - BACKGROUND: Contemporary, not very frequent studies have brought only few and
      often inconsistent findings about the significance of cytoadhesive molecules
      (CAM) type "vascular cell adhesion molecule-1" (VCAM-1) and "intercellular cell
      adhesion molecule-1" (ICAM-1) at multiple myeloma (MM). The aim of the study was
      to interpret relations among levels of soluble forms of VCAM-1 and ICAM-1 in
      serum of the peripheral blood (SPB) and in serum of the aspirated bone marrow
      (SABM) to concentrations of selected elements of the cytokine network (IL-2, sIL
      2R, IL-6, sIL-6R, and TNF-alpha) during different phases of MM disease and to
      recognise whether there are some specific relations of these factor in both
      tissue fluids. METHODS AND RESULTS: Two groups of patients with MM were analysed:
      the group of 64 patients examined in different phases of MM disease and group of
      39 patients examined when the disease was diagnosed (age median was 63 and 64
      years, male to female relation was 1.6 and 1.3 to 1.0). CAM, cytokine and their
      soluble receptor levels were estimated using ELISA method. Increased levels of
      sVCAM-1 in APB were found in 87.5 and 87% of patients; in both groups sVCAM-1
      medians almost twice exceeded the upper limits of normality (1180 and 1295
      ng/ml). Levels in SABM were always higher (1347 and 1546 ng/ml) than that in SPB.
      Higher values of sICAM-1 in SPB had 35 and 33% of patients; sICAM-1 medians in
      SPB and in SABM did not exceed in either group the upper limits of normality (691
      ng/ml) and they did not differ significantly (519 vs 476 and 518 vs 500 ng/ml).
      Statistical analysis (Pearson's correlation quotient, p < 0.05) has shown in both
      groups significant relation among sVCAM-1 in SPB and SABM levels (p-0.0001 and p
      0.0012) and sICAM-1 level (p-0.0002 and p-0.0011) in both types of tissues
      fluids. In the larger group the statistically significant relation of sVCAM-1 in
      SPK to sIL-2R (0.0001), sIL-6R (0.0001), TNF-alpha (0.0003), and sICAM-1 (0.042)
      was found as well as to IL-2 (0.034, sIL-6R (0.044), and sICAM-1 (0.007) in SABM.
      In the group of 39 patients examined when the MM disease was diagnosed, relation
      of sVCAM-1 in SPB to levels of sIL-6R (0.0002) and TNF-alpha (0.0001), and in
      SABM only to sIL-2R (0.009). Evaluation of sICAM-1 revealed relation only to
      levels of sVCAM-1 both in SPK (0.042) and in SABM (0.007) in the larger group of
      patients. CONCLUSIONS: The described concentration changes of soluble CAM in
      serum of the peripheral blood and in serum of the aspirated bone marrow as well
      as identified relations to levels of various elements of the cytokine network
      indicate that CAM and especially sVCAM-1, together with elements of the cytokine
      network play a role in the complicated MM pathology. Particular activity of serum
      soluble forms sVCAM-1 and sICAM-1 in the pathogenesis of myeloma has not been
      clarified. It shows that analysis of soluble cytoadhesive molecules sVCAM-1 and
      sICAM-1 and selected elements of the cytokine network (IL-2, sIL-2R, IL-6, sIL-6R
      and TNF-alpha) in serum of the aspirated bone marrow has no advantage to analysis
      of the peripheral blood serum.

PMID- 10971971
TI  - [Malignant stenosis of the superior vena cava].
AB  - Superior vena cava syndrome is a distressing manifestation of a benign or
      malignant disease that obstructs the blood flow in the superior vena cava.
      Radiation and chemotherapy are often used to treat malignant forms of the
      disease. However, this therapy brings slow and sometimes incomplete regression of
      symptoms. Percutaneous administration of the metallic intravascular stents
      appears to be effective therapy. It offers immediate resolution and long-term
      relief of symptoms. Paper describes two patients with superior vena cava syndrome
      of a malignant aetiology where the incomplete but hemodynamicaly significant
      stenosis was successfully treated by percutaneous stenting.

PMID- 10971972
TI  - Audit, ethics and the scientific process.

PMID- 10971973
TI  - Clinical audit: essential input for enhancing standards of care.

PMID- 10971974
TI  - Specialty choices of male and female doctors in Malaysia.
AB  - A survey of specialisation choices was conducted for two batches of medical
      officers applying to the local medical schools for specialisation in Malaysia. A
      total of 359 doctors responded, giving a response rate of 71%, with 169 male
      (44.4%) and 187 female (55.6%) respondents. Surgery ranked highest among the male
      doctors followed by orthopaedic surgery and internal medicine. Family medicine
      ranked highest among female doctors followed by public health and
      anaesthesiology. Among the other specialties, the male doctors preferred
      otorhinolaryngology while female doctors preferred Pathology. Both male and
      female doctors chose to be a clinical consultant in a general hospital as the
      first choice. They prefer to work in or near their hometowns.

PMID- 10971975
TI  - A 2-year audit of perioperative mortality in Malaysian hospitals.
AB  - An audit of all perioperative deaths within seven days of surgery in 14 major
      public hospitals is presented. This study is part of a quality assurance
      programme examining the surgical and anaesthetic practices in these hospitals.
      During the study period from July 1992 till June 1994, 211,354 surgeries were
      performed and 715 deaths were reported out of which 699 were available for
      analysis. The data was obtained by confidential enquiry using predetermined
      questionnaires filled by participating surgeons and anaesthetists and analysed by
      a group of peers. The overall crude mortality rate was 0.34% and the majority of
      the deaths occurred in severely ill patients in whom the clinical management was
      satisfactory. Polytrauma including head, intra-abdominal and skeletal trauma
      accounted for 253 of the deaths (36.19%). The other causes were bowel obstruction
      with sepsis, burns, ischaemic limbs, congenital malformations in neonates and
      pregnancy-related hemorrhage. 62.52% of the deaths occurred within two days of
      surgery and 85.87% were related to emergency procedures. The review identified
      some shortfalls in perioperative care and these were lack of adequate critical
      care facilities, lack of supervision, unnecessary surgery in the moribund and
      inadequate preoperative optimisation. The results of the study have been
      forwarded to all participating hospitals for implementation of remedial measures.

PMID- 10971976
TI  - Linking death reports from the Malaysian Family Life Survey-2 with birth and
      death certificates.
AB  - The Malaysian Family Life Survey--2 (MFLS-2) was a population-based survey
      conducted in Peninsular Malaysia in 1988-89. Through detailed birth histories, it
      attempted to collect information on all pregnancies and their outcomes from ever
      married women, as well as socioeconomic and health services-utilization data that
      might have affected mortality. The survey did not, however, collect information
      on the causes of infant death. The two objectives of this study were to assess
      the feasibility of linking all reported deaths among live births of women
      interviewed in the MFLS-2 to the birth and death certificates kept by the
      National Registration Department, and to determine the causes of death from the
      successfully matched death certificates. This information could be used in the
      development of specific health programs to decrease infant and child mortality.
      In this study, the success rates for linking survey data to birth and death
      certificates were 34.5% and 31.8% respectively. Methodological problems faced
      during the study are discussed, as are the strengths and limitations of record
      linking as a means of increasing the utility of birth histories for studying the
      causes of death. Ways to improve linkage rates of survey data with the national
      birth and death registration are also suggested.

PMID- 10971977
TI  - Exposure to sputum positive cases of tuberculosis in a government hospital.
AB  - A retrospective study was carried out to ascertain the degree of exposure to the
      tubercle bacillus within Ipoh Hospital. This study reveals that, over a one year
      period, 92 sputum positive cases were admitted to the general wards. In 11 of
      these cases, drug resistance was considered to be possible. The mean time from
      admission to the commencement of treatment was seven days for the newly diagnosed
      cases. This study thus documents a significant degree of in-hospital exposure to
      the tubercle bacillus.

PMID- 10971978
TI  - Blood transfusion reactions in Malaysian newborn infants.
AB  - A prospective observational study was carried out over a seven month period in
      the neonatal intensive care unit (NICU) of a large Malaysian maternity hospital
      to determine the rate of blood transfusion and the incidence of transfusion
      reactions in newborn infants. During the study period, the rates of blood
      transfusion was 6.1% (n = 117) of NICU admission or 8.2 per 1,000 live births.
      The median birth weight of the infants who had received blood transfusion was
      1,740 grams (range: 725-4,350), and their mean gestational age was 33.6 weeks (sd
      = 5.1, range = 24-41 weeks). The median age of infants when they first received
      blood transfusion was 4.0 days (range: 1-27 days). When compared with infants of
      birth weight between 3,000 and 3,499 grams, infants of birth weight less than
      1,500 grams received significantly higher median number of transfusions per
      infant, (p < 0.001). The incidence of transfusion reaction was 2.7% (3/110) of
      all transfused infants or 1.3% (3/223) of all blood transfusions. Febrile
      nonhemolytic reaction was the only type of transfusion reaction detected during
      the study period. This study showed that transfusion reactions in newborn infants
      were not common.

PMID- 10971979
TI  - A double blind comparison of zuclopenthixol acetate with haloperidol in the
      management of acutely disturbed schizophrenics.
AB  - The aim of this study was to evaluate the efficacy and side effects of
      zuclopenthixol acetate compared with haloperidol in the management of the acutely
      disturbed schizophrenic patient. Suitable subjects diagnosed as having
      schizophreniform disorder or acute exacerbation of schizophrenia admitted to the
      psychiatric wards Hospital Kuala Lumpur were randomised to receive either
      zuclopenthixol acetate or haloperidol. They were rated blind for three
      consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global
      Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the
      same medication, no other anti-psychotic was given for the duration of the study.
      50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol
      acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores
      on all 3 days compared to the initial rating (p < 0.001). There was however no
      difference between the zuclopenthixol acetate and haloperidol group scores on all
      days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more
      than 1 injection during the study. Both groups had minimal side effects.
      Zuclopenthixol acetate was effective in the management of the acutely disturbed
      schizophrenic.

PMID- 10971980
TI  - A 3 year audit of infected pseudoaneurysms in intravenous drug users managed
      surgically in the Vascular Unit, Hospital Kuala Lumpur.
AB  - This is a study of 54 intravenous drug user's (IVDUs) with infected
      pseudoaneurysms undergoing ligation and debridement at the Vascular Unit,
      Hospital Kuala Lumpur (HKL) from February 1993 to February 1996. The median age
      was 37 years with a male preponderance (53:1). Chinese form the largest ethnic
      group with 57.4% of the cases. Staphylococcus aureus was the most common organism
      cultured. Human immunodeficiency virus (HIV) positive cases numbered 21 (38.9%).
      Four of the patients had to have an above-knee amputation after surgery. Simple
      ligation and debridement of all necrotic tissue is an acceptable mode of therapy
      in these patients with low amputation rates.

PMID- 10971981
TI  - The effectiveness of surfactant replacement therapy for preterm infants with
      respiratory distress syndrome.
AB  - Thirty preterm infants weighing > or = 800 g with clinical and radiological
      evidence of respiratory distress syndrome (RDS) requiring mechanical ventilation
      with FiO2 of > or = 40% were given modified bovine surfactant (Survanta). They
      were compared with equal number of historical controls. Infants who received
      surfactant showed prompt and highly significant improvement in FiO2, mean airway
      pressure, arterial/alveolar oxygen tension ratio and ventilatory index. There was
      significant improvement in mortality rate (10% vs 33%; p = 0.03). Among the
      survivors, surfactant-treated infants required shorter duration of continuous
      positive airway pressure (CPAP) (3.4 vs 9.6 days; p = 0.04). For survivors with
      birthweight of > 1000 g, surfactant-treated infants required shorter duration of
      ventilatory support (intermittent positive pressure ventilation + CPAP) (7.5 vs
      18.9 days, p = 0.02). Overall, surfactant-treated infants achieved full enteral
      feeds sooner (15.7 days vs 24.6 days; p = 0.03) and required shorter duration of
      total parenteral nutrition (13.9 days vs 25.6 days; p = 0.02). We concluded that
      surfactant replacement therapy was effective in the treatment of preterm infants
      with RDS.

PMID- 10971982
TI  - An application of the backcalculation method to estimate past HIV infection rates
      in Malaysia.
AB  - The method of backcalculation estimates past HIV infection rates from available
      AIDS incidence data and an estimate of the incubation period. The method is used
      on the Malaysian data to model the AIDS epidemic because it makes use of the
      Malaysian AIDS incidence data which is fairly reliable and is more reflective of
      the trend of the epidemic as compared to the HIV infection rate recorded. An
      application is made on the monthly AIDS incidence data in Malaysia from January
      1995 until August 1996 released by the Ministry of Health, Malaysia using the
      backcalculation program from Bacchetti et al and the incubation period
      distribution from Brookmeyer to generate the current HIV infection rate for
      Malaysia (until August 1996).

PMID- 10971983
TI  - Reliability, validity and discriminatory ability of Spitzer's QL-index in
      dialysis patients.
AB  - Quality of life outcome (QOL) on dialysis is important. We determined the
      measurement properties of Spitzer's QL-index, a QOL measure, in our patients on
      chronic haemodialysis. The QL-index measures 5 dimensions of QOL (activity, daily
      activities, general health, social support and psychological outlook). 59
      haemodialysis (HD) patients from 2 centres were rated by 5 raters. Inter-rater
      agreement for the total score was good with a mean intra-class correlation
      coefficient 0.66 (range 0.47-0.81). That for dimension scores however was poor
      (weighted kappa range 0.07-1). Systematic differences between raters were also
      observed. Intra-rater agreement was generally better than inter-rater agreement.
      Significant gradients in scores were observed by age, serum albumin, comorbid
      disorders, previous hospitalisation, capacity for self care HD and rehabilitation
      status thus providing evidence for construct validity. The distribution of total
      scores was skewed indicating poor discriminatory ability. Nevertheless, QL-index
      has acceptable measurement properties for application in dialysis patients.

PMID- 10971986
TI  - Percutaneous central venous catheterisation in critically ill children.
AB  - An 18-month analysis of 52 percutaneously placed central venous catheters in 48
      critically ill children was done. Success rate were 91.7% (33/36) and 93.8%
      (15/16) for femoral and non-femoral catheters respectively. Presence of
      hypotension (48.1%) and significant coagulopathy (26.9%) did not affect the
      success rate significantly. Minor bleeding and venous congestion was seen in 5.5%
      (2/36) of patients with femoral catheters. Infections were found in 2.7% (1/36)
      of femoral and 6.6% (1/15) of non-femoral catheters. The low incidence of
      complications and the relative ease of insertion makes the femoral route the
      preferred site for trainee medical officers in critically ill children when
      central access is indicated.

PMID- 10971984
TI  - Some risk factors of Ascaris and Trichuris infection in Malaysian aborigine
      (Orang Asli) children.
AB  - A study on risk factors of soil-transmitted helminths was conducted in a highly
      endemic area. In all 205 children (95 boys and 110 girls) participated in this
      study. The overall prevalences of Ascaris, Trichuris and hookworm infection were
      62.5%, 91.7% and 28.8% respectively. Only 22.4% of the children had a single
      infection either by Ascaris or Trichuris; 69.3% had mixed infection and the most
      prevalent of mixed infection was a combination of Ascaris and Trichuris. Logistic
      regression analysis confirmed that low level mother's education was a risk factor
      for moderate and severe infection of Ascaris and age < or = 6-year-old was a
      protective factor. In Trichuris infection logistic regression analysis confirmed
      that usage of well-water and age < or = 6-year-old were the risk factors.
      Logistic regression analysis on worm scores confirmed that usage of well-water
      and non-usage of toilets were the risk factors from getting severe worm scores
      and age < or = 6-year-old was a protective factor. Our finding suggest that socio
      behavioural (related to mother's education), demographic (children age) and
      environmental-factors (usage of well-water and non-usage of toilets) are the
      elements to be considered in the design of long term soil-transmitted helminths
      (STH) control in an endemic areas.

PMID- 10971985
TI  - Efficacy of albendazole in the treatment of Trichuris trichuria and Giardia
      intestinalis infection in rural Malay communities.
AB  - A community study was carried out to evaluate the efficacy of a 3-day course of
      400 mg albendazole daily in the treatment of Trichuris trichiura and Giardia
      intestinalis infection. This treatment regimen was effective in the treatment of
      Trichuris trichiura and Giardia intestinalis infection with cure rates of 91.5%
      and 96.6% respectively. Uses of a 3-day course of 400 mg albendazole daily should
      be considered in mass or targeted soil-transmitted helminths chemotherapy
      particularly in areas where the prevalence of Trichuris trichiura is high and
      polyparasitism is common.

PMID- 10971987
TI  - Parotid swellings: report of 110 consecutive cases.
AB  - Parotid swellings are uncommon. Over a twelve-year period, 110 cases of parotid
      swellings were treated at the Department of Plastic Surgery, Hospital Kuala
      Lumpur, of which 97 cases were histologically proven to be parotid tumours. 75%
      of these tumours were benign tumours, and 80% of the benign tumours were
      pleomorphic adenomas. Among the malignant tumours, 6 cases were adenoid cystic
      carcinoma and 5 were carcinoma ex-pleomorphic adenoma. There were equal number of
      male to female patients, with an age range of 14 to 83 years. There is a positive
      correlation between the final histological diagnosis and FNAC results in 74% of
      cases. Surgical treatment of choice for benign parotid tumours was near-total
      parotidectomy whilst for malignant tumours was total radical parotidectomy with
      sural nerve graft.

PMID- 10971988
TI  - Profile of patients with abdominal aortic aneurysm referred to the Vascular Unit,
      Hospital Kuala Lumpur.
AB  - A prospective collection of patients referred with a diagnosis of abdominal
      aortic aneurysm (AAA) to the Vascular Unit, Hospital Kuala Lumpur (HKL) between
      February 1993 to July 1995 were analysed. There were a total of 124 patients,
      with a 85 per cent (%) male preponderance. Malays formed the largest ethnic group
      contributing about 60%. The median age of the patients was 69 years (range 49
      84). Emergency referrals and admission accounted for 46.8% of patients.
      Hypertension and ischaemic heart disease were the two most common co-morbid
      medical conditions. The number of patients who underwent surgery was only 56
      (45.2%). Of this total, 34 were done electively with an operative mortality of
      8.8% (3 pts). The operative mortality for emergency surgery was 59.1%. AAA is
      relatively common in the older age group, especially in men and it should be
      actively looked for, as elective surgery can be offered with acceptable morbidity
      and mortality.

PMID- 10971989
TI  - Pressure ulcers--randomised controlled trial comparing hydrocolloid and saline
      gauze dressings.
AB  - An open comparative randomised study comparing the performance of hydrocolloid
      dressings (DuoDERM CGF) to saline gauze dressings in the treatment of pressure
      ulcers was done to evaluate the overall dressing performance, wound healing and
      cost effectiveness. Thirty-four subjects were enrolled at the University
      Hospital, Kuala Lumpur over a 643 days period. Inclusion criteria were Stage II
      or III pressure ulcers, at least 18 years of age and written informed consent.
      Only one pressure ulcer per subject was enrolled in the study. Patients with
      infected pressure ulcers, diabetes mellitus, an immuno-compromised status and
      known sensitivity to the study dressings were excluded. Subjects who met the
      enrollment criteria were randomised to one of the two dressing regimes. They were
      expected to participate in the study for a maximum of eight weeks or until the
      pressure ulcer healed, which ever occurred first. Overall subject age averaged 58
      years and the mean duration of pressure ulcer existence was about 1 month. Twenty
      one of the thirty-four ulcers enrolled were stage II and thirteen were stage III.
      The majority of the ulcers (88%) were located in the sacral area and seventeen
      subjects (50%) were incontinent. In the evaluation of dressing performance in
      terms of adherence to wound bed, exudate handling ability, overall comfort and
      pain during dressing removal; all favoured the hydrocolloid dressing by a
      statistically significant margin (p < 0.001). Subjects assigned the hydrocolloid
      dressing experienced a mean 34% reduction from their baseline surface area
      measurement compared to a mean 9% increase by subjects assigned gauze dressings.
      This was not statistically significant (p = 0.2318). In cost evaluation of the
      study products, there was no statistical significance in the total cost of wound
      management per subject. When only labour time and cost was evaluated, there was a
      statistically significant advantage towards hydrocolloid dressings.

PMID- 10971990
TI  - Hypercalcaemic crisis as the presenting manifestation of abdominal tuberculosis:
      a case report.
AB  - This report deals with a young man having prolonged fever presenting with
      hypercalcaemic crisis. Subsequent investigations confirmed tuberculosis (TB)
      peritonitis in the absence of pulmonary involvement as the cause of his symptoms.
      His hypercalcaemia and fever resolved with anti-TB therapy. Abdominal TB needs to
      be included in the differential diagnosis of otherwise unexplained hypercalcaemia
      especially in our region where TB is an endemic problem and is treatable.

PMID- 10971991
TI  - Progressive septal and palatal perforation secondary to intranasal cocaine abuse.
AB  - Septal perforation from intranasal cocaine abuse is well recognised. We present a
      case of progressive septal as well as palatal perforation. Progression from
      septal perforation to palatal perforation occurred after cessation of intranasal
      cocaine abuse. This patient had a weakly positive cytoplasmic antineutrophilic
      cytoplasmic antibody (C-ANCA) but no histologic evidence of Wegener's
      Granulomatosis. The differential diagnosis for septal and palatal perforation is
      reviewed. This case represents the fifth reported case of palatal perforation
      secondary to cocaine abuse in the literature, and the second associated with
      positive C-ANCA.

PMID- 10971992
TI  - Central serous choroidopathy in pregnancy.
AB  - Central serous choroidopathy is a spontaneous serous detachment of the sensory
      retina, usually affecting adults between 20 to 50 years of age but is also found
      in patients older than 60 years of age. This disease usually affects males with a
      male to female ratio of 8-10 to 1. Many aetiological or associated factors have
      been described. Here we report a 39-year-old pregnant lady presented with left
      central serous chorioretinopathy preceded by an unusual emotional disturbance.
      She was not given any photocoagulative treatment to avoid possible
      photocoagulative complications. Post delivery, she presented with resolution of
      the CSC.

PMID- 10971993
TI  - Fatal early-onset neonatal sepsis due to Streptococcus pneumoniae.
AB  - Two cases of invasive early-onset neonatal pneumococcal sepsis are reported. One
      neonate was born at term with no risk factors and the other preterm at 35 weeks.
      Sepsis was not detected at birth for either of these babies and diagnosis was
      made at the stage of severe sepsis. A fatal outcome resulted despite treatment.
      Pneumococcal sepsis was confirmed after death in both these cases. Although
      maternal carriage was not documented in either case, the ages at presentation and
      progression suggested perinatal acquisition of infection. Early onset neonatal
      pneumococcal sepsis presents similarly as early onset neonatal Group B
      streptococcal (GBS) sepsis. Vaginal carriage of pneumococcus is rare but the
      micro-organism may have a higher invasion to colonisation ratio (attack rate)
      than GBS. Risk factors for invasive disease are similar to GBS.

PMID- 10971994
TI  - Lower lip numbness due to peri-radicular dental infection.
AB  - Lower lip numbness has always been a sinister symptom. Much has been written
      about it being the sole symptom of pathological lesions and metastatic tumours in
      the mandible. It may also be a symptom of manifestations of certain systemic
      disorders. A case of lower lip numbness resulting from the compression of the
      mental nerve by a peri-radicular abscess is presented because of the unusual
      nature of this spread of infection.

PMID- 10971995
TI  - Survey on health status of heavy vehicle drivers in Klang valley.
AB  - A survey was carried out using a medical examination format that was prepared by
      the Malaysian Medical Association. The findings of the survey show that of the
      266 cases surveyed, 64 drivers (24% of cases surveyed) are either totally unfit
      to drive or temporarily unfit to drive heavy goods and passenger vehicles. This
      is clear indication that the current format that is being used by the Road
      Transport Department is inadequate and needs to be reviewed. It must also be
      stressed that all the above 64 drivers have been certified fit using the existing
      Road Transport Department format and are currently driving in our highways and
      roads. Heavy vehicle goods and passenger vehicle drivers if not properly examined
      and medically certified are not only be endangering their own lives but also that
      of others. It is therefore recommended that based on the data available from this
      survey, the Road Transport Department should seriously consider adopting the
      medical examination format that was formalised by the Malaysian Medical
      Association and used in this survey.

PMID- 10971997
TI  - Safety with anaesthesia--the paradigm of continuous improvement.

PMID- 10971996
TI  - Managing the solitary thyroid nodule.
AB  - Solitary thyroid nodules are commonly seen in surgical outpatient clinics. A
      detailed history and a careful physical examination are essential. In the
      management of the solitary thyroid nodule, fine needle aspiration cytology has
      become the cornerstone investigation. Ultrasound cannot differentiate between
      benign and malignant nodules, however is useful in the follow-up period to
      identify any further nodular growth. As thyroid malignancy occurs in both hot and
      cold nodules, radionuclide scans are not useful in the management of solitary
      thyroid nodules. We have attempted to outline the process of managing the
      solitary thyroid nodule and discuss the options available.

PMID- 10971998
TI  - Anaesthesia Incident Monitoring Study in Hospital Kuala Lumpur--the second
      report.
AB  - Critical incident reporting is a useful quality improvement technique for
      reducing morbidity and mortality in anaesthesia. This study analyses 93 cases in
      Kuala Lumpur Hospital from July 1995 to January 1997. The main incidents during
      anaesthesia in this study were airway incidents. While human error was identified
      as the main factor contributing to the occurrence of adverse incidents. Critical
      incident monitoring plays an important role in identifying potential problems,
      which may lead to disaster. The findings from this report of the anaesthesia
      incident monitoring study continued to indicate the occurrence of similar
      problems seen in an earlier report. The identification of common incidents can be
      used to identify risk factors and minimise repetition of such incidents.

PMID- 10971999
TI  - Peak expiratory flow rate in elderly Malaysians.
AB  - An epidemiological survey was conducted among 1,414 healthy ambulatory elderly
      persons aged 55 years and above in the Kuala Langat district, Selangor. The
      relationship between peak expiratory flow rate (PEFR), demographic variables,
      socioeconomic status, smoking, alcohol use and respiratory symptoms were
      examined. The peak expiratory flow declined with age and were lower in women of
      all ages. Smoking had a modest effect on PEFR in men but not on PEFR in women.
      The combination of respiratory symptoms of cough, phlegm and wheeze were related
      to lower PEFR values. Prediction equations are presented derived from the
      population sample which may be of assistance in assessing observed to expected
      ratios among elderly people in Malaysia.

PMID- 10972000
TI  - Pre-admission management of acute gastroenteritis in children: too much or too
      little?
AB  - Two hundred and ninety five children admitted with acute gastroenteritis from
      January 1, 1996 to December 31, 1996 to the Paediatric unit, University of Malaya
      Medical Centre, Kuala Lumpur, were reviewed. Eighty-nine percent of children
      received treatment before admission. Information regarding the type of treatment
      received were available in 152 (52%) cases. Eighty percent of them were
      prescribed medications, 40% were prescribed glucose-electrolyte mixtures, and 13%
      were advised a change of formula. Only 18 children (12%) were advised to take
      glucose-electrolyte mixtures alone. The four most common prescribed drugs were:
      antibiotics (43%), antipyretics (39%), antidiarrhoeal agents (30%), and
      antiemetics (24%). The use of antibiotics, antiemetics and antidiarrhoeal drugs
      for children with acute gastroenteritis among primary care doctors appears to be
      common. The use of glucose-electrolyte mixtures was uncommon.

PMID- 10972001
TI  - Prevalence of latex hypersensitivity among health care workers in Malaysia.
AB  - Health care workers have been reported to constitute one of the few high-risk
      groups related to IgE-mediated hypersensitivity associated with the use of latex
      products. This paper describes the first ever study of prevalence carried out in
      Malaysia among these workers. One hundred and thirty health care personnel from
      Hospital Kuala Lumpur were skin tested. Extracts used were prepared from seven
      different brands of natural rubber latex gloves with varying levels of
      extractable protein (EPRRIM). Out of the 130 volunteers, 4 (3.1%) had positive
      skin test to latex with extracts with high levels of EPRRIM (> 0.7 mg/g). The
      prevalence among the Malaysian health care workers can be considered to be low in
      comparison to that of some consumer countries as the USA which reported a
      prevalence of as high as 16.9%.

PMID- 10972002
TI  - Uvulo-palatoglossal junctional ulcers--an early clinical sign of exanthem subitum
      due to human herpesvirus 6.
AB  - A provisional clinical diagnosis of exanthem subitum was made in six febrile
      infants seen in the Paediatric Unit of Assunta Hospital, Petaling Jaya, Malaysia
      with uvulo-palatoglossal junctional ulcers prior to the eruption of maculopapular
      rash. On follow-up, all six infants developed maculopapular rash with the
      subsidence of fever at the end of the fourth febrile day. Human herpesvirus 6 was
      isolated from the peripheral blood mononuclear cells during the acute phase of
      the illness and HHV 6 specific genome was also detected in these cells by nested
      polymerase chain reaction. All the six infants showed seroconversion for both
      specific IgG and IgM to the isolated virus. This study suggests that the presence
      of uvulo-palatoglossal junctional ulcers could be a useful early clinical sign of
      exanthem subitum due to human herpesvirus 6.

PMID- 10972003
TI  - Patients' knowledge and attitude towards treatment and control of hypertension: a
      nation-wide telephone survey conducted in Malaysia.
AB  - The telephone survey of 2,526 hypertensive subjects showed 94% of the respondents
      were aware of the importance in controlling hypertension. Among these 504 were
      not on anti-hypertensive medication while the majority of 2,022 were currently on
      anti-hypertensive medication. Of those who were not on medication, 80% (n = 403)
      were found non-hypertensive on follow-up. The remaining 20% (n = 101) were
      confirmed hypertensive and were offered medication. However, 38 subjects refused
      to take medication and 63 subjects complied with medication but subsequently gave
      up. The main reasons for giving up medication included lack of motivation (38%),
      doctors' advice (20%), side effects (19%) and concern of side effects (10%). Of
      2,022 hypertensive respondents who were currently on medication, almost half
      (44%, n = 890) required a change of medication due to side effects (40%, n = 356)
      or the blood pressure not controlled with the previous medication (33%, n = 294).
      Despite the change in medication, 42% (n = 150) still continued to suffer from
      some form of side effects. The information obtained from this survey suggested it
      is important to recommend some strategies to improve patient compliance. These
      strategies comprise of motivating the patient, improving medication with less
      side effects, improving potency and efficiency of medication, and reduction of
      cost in medication. In addition, convenient blood pressure monitoring such as
      home blood pressure monitoring is also encouraged.

PMID- 10972004
TI  - Outpatient procedures for cervical dysplasia: a 3 year review of laser
      vaporisation and LEEP.
AB  - A 3 year retrospective review (1995 to 1997) of 127 patients with cervical
      dysplasia who underwent Laser Vaporisation of the cervix and LEEP at the
      Gynaecological Cancer Centre, KK Women's & Children's Hospital, Singapore, was
      undertaken. Amongst the patients in the Laser Vaporisation group, the mean age
      was 37.7 years (SD 8.8), the mean operating time was 14.8 minutes (SD 8.5), 63.6%
      were given prophylactic antibiotics and the mean follow up period was 15.3 months
      (SD 12.0), whilst in the LEEP group, mean age was 40.3 years (SD 8.4), mean
      operating time, 11.8 minutes (SD 4.9), prophylactic antibiotic rate, 53.8% and
      mean follow up period was 19.1 months (SD 9.3). Mild and moderate haemorrhage
      post procedure were the only complications encountered, 10.2% (5/49) in the Laser
      group and 3.8% (3/78) in the LEEP group. 98% (48/49) and 97.4% (76/78) of the
      Laser and LEEP groups, respectively, were free of disease on follow up. None of
      the 3 patients with persistent or recurrent disease were diagnosed as having
      invasive cancer. Overall, there were no significant differences in the patient
      characteristics, histopathology, operating times, follow up period, the use of
      prophylactic antibiotics, and complications in the 2 groups. The low complication
      rate, high disease-free rate and the relatively short operating time of Laser
      Vaporisation and LEEP in our study suggests that, indeed, both the procedures can
      be done safely and efficiently in the outpatient setting. However the discrepancy
      between the histology of colposcopically directed biopsy and that of LEEP
      specimens suggests that colposcopically directed biopsy may not be as accurate as
      one might believe, and further studies analysing the concordance between
      colposcopically directed biopsy and LEEP biopsy histologies are needed.

PMID- 10972005
TI  - Nosocomial bacterial sepsis in babies weighing 1000-1499 g in Kelantan.
AB  - From January to December 1992, 92 babies weighing 1000-1499 gm here to referred
      as very low birth weight (VLBW) were admitted to NICU (Neonatal Intensive Care
      Unit), Hospital University Sains Malaysia (HUSM). Sixty babies were inborn giving
      a VLBW rate of 7.5 per 1000 live births. Incidence of nosocomial sepsis was 32.6%
      (30/92) of whom 43.3% (13/30) died. Eighty percent (24/30) of the septic babies
      had blood culture positive for gram negative organisms of which 40% (12/30) were
      sensitive only to imipenem. Ventilator support within 24 hours of life was
      required in 41.3% (38/94) babies of whom 42% (16/38) babies developed nosocomial
      sepsis. Delayed initiation of feeding was significantly associated with
      nosocomial sepsis. A strict asepsis policy and early feeding of the VLBW infant
      are essential components of any strategy to prevent of sepsis due to nosocomial
      infection.

PMID- 10972006
TI  - The association of uvulo-palatoglossal junctional ulcers with exanthem subitum: a
      10-year paediatric outpatient study.
AB  - A 10-year follow-up of children having exanthem subitum (ES) seen in an
      outpatient paediatric clinic, Kuala Lumpur, Malaysia shows that uvulo
      palatoglossal junctional (UPJ) ulcer is a reliable early clinical sign of ES.
      During this period, 1,977 children (1,086 males, 891 females) had adequate follow
      up from the age of 3 months to 24 months old. 897 children (478 males, 419
      females) were noted to have UPJ ulcers. Of these 897 children, 855 (459 males,
      396 females) presented with the classical clinical features of ES of
      maculopapular rash following 3 to 4 days of fever. The positive predictive value
      and the negative predictive value of UPJ ulcers in the clinical diagnosis of ES
      are 95.3% and 100% respectively. Among the 855 children with clinical features of
      ES, a provisional diagnosis of ES could be made in 781 children during the pre
      eruptive phase by the presence of the UPJ ulcers. The other 74 children already
      had the rash at the time of consultation at the clinic. The peak age of
      occurrence of ES was 6 months old with 98.2% of the total cases of ES seen
      between the age of 4 and 12 months. There was no significant gender difference in
      the incidence of ES nor any seasonal variation. Mild to moderate diarrhoea was
      the other commonly associated clinical feature which usually presented from the
      third febrile day onwards.

PMID- 10972007
TI  - Assessing the status of intrauterine insemination before forming a medically
      assisted conception unit.
AB  - A survey in 1996 of our female patients suggest that the three commonest causes
      of infertility were endometriosis, anovulation and idiopathic which comprises of
      about 70% of all the patients. In the male patients, sperm morphology evaluation
      by critical criteria showed that abnormal morphology was present in 71% while 87%
      of all the semen analysis were abnormal. The objective of this study was to
      assess the status of IUI before proceeding to formulate patient protocols for IVF
      in a tertiary infertility referral unit. A retrospective study of patients data
      was done from Jan 1995 to Dec 1996. Ovarian stimulation by clomiphene for
      anovulatory and idiopathic patients was performed on couples with at least one
      patent fallopian tube. Ovulation induction was by an intramuscular injection of
      5000 i.u of HCG after follicular maturation. IUI was performed approximately 36
      40 hours later. A total of 74 couples received 114 treatment cycles producing a
      total of 9 conceptions. The conception rate of IUI was therefore 7.89% per cycle
      and 12.16% per couple with the cumulative pregnancy rate of 28.21%. Associated
      success features of IUI found in this study were the age of the woman and the
      semen parameters of the husband.

PMID- 10972008
TI  - Compliance with monitoring standards for anaesthesia in Malaysian hospitals.
AB  - The Malaysian Society of Anaesthesiologists published a document entitled
      "Recommendations for Standards of Monitoring during Anaesthesia and Recovery" in
      1993. This paper examines the results of two surveys, carried out in 1995 and
      1996 respectively; to determine compliance with published Monitoring Standards in
      Malaysian public and private hospitals. In the private sector, compliance with
      the recommended standards during anaesthesia varied greatly. Of the 28 government
      hospitals surveyed in 1996, compliance with monitoring standards during
      anaesthesia was almost 100%. Standards in recovery areas were less than ideal.
      The majority of anaesthesiologists thought that the current recommended standards
      were adequate.

PMID- 10972009
TI  - Profile of patients seen at a psychosexual clinic in a gynaecological teaching
      hospital--the Singapore experience.
AB  - Ignorance is not bliss when it comes to sexuality. Psychosexual problems lead to
      shame, fumbling, needless fears, low-self esteem and even subfertility. The
      demands for help appears to be increasing; as the general population become more
      aware of its presence and the treatment options available through the mass media
      and better health education. Sex therapy has traditionally been the realm of the
      psychiatrist but with the gynaecologist as the first contact for most women, the
      number of women seeking advice directly from their doctors will only increase
      with time. A total of 243 new cases of sexual dysfunction were treated at the
      sexual problem clinic in Kandang Kerbau Hospital between January 1994 and
      November 1996; majority of which were self-referrals (48.5%). The patient pool
      consisted of more males than females although the clinical setting is in an
      obstetrics and gynaecology teaching institute. Vaginismus and erectile problems
      constituted the main complaints. Erectile problems are more common in the
      patients above 40 years old (p < 0.001). We report here our experience of such a
      sexual problem clinic and hope to provide insight into this area of medicine from
      the perspective of a practising gynaecologist.

PMID- 10972010
TI  - Parents' awareness and knowledge of the special needs of their hearing-impaired
      child.
AB  - We surveyed parents of school-aged hearing impaired children to investigate their
      awareness and knowledge of the special needs of their child, especially in the
      area of the usage of hearing aids and methods of communication. Questionnaires
      were distributed to parents of hearing impaired children at 13 special schools
      for the deaf in Malaysia. Out of 1,267 questionnaires given out, 787 (62.1%) were
      completed and returned. Results of the survey indicated the majority of parents
      (68.6%) suspected hearing loss late, that is after their child's first birthday,
      and there was a significant time lag before the suspicion was confirmed. Over
      82.8% of the children were diagnosed only after 1 year of age, with 41.3% being
      diagnosed after 3 years of age. Hearing aids were fitted late (mean = 5.32 years;
      SD = 2.66). Hearing aid ownership was influenced by the factors of socio-economic
      level and ethnic group (p < 0.01) whereas knowledge of use and proper care of the
      aids was influenced by socio-economic level (p < 0.01). Communication methods
      were generally inappropriate with 41.3% of the mothers and 48.5% of the fathers
      reporting ignorance of Bahasa Malaysia Kod Tangan, the sign language that is
      commonly used by their children. The parents' choice of communication method was
      not significantly influenced by socio-economic level or ethnic group. The study
      revealed the present inadequate state of services available for the
      rehabilitation of children with congenital hearing impairment.

PMID- 10972011
TI  - Intestinal helminth infections amongst school children in the Serian District of
      Sarawak.
AB  - School children from 3 primary and 2 secondary schools in Sarawak were examined
      for the presence of gastrointestinal helminths. One primary school and 1
      secondary school were located in a town (Serian), the other primary and secondary
      schools were in the countryside outside Serian. The intestinal helminths detected
      were Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis and
      hookworm. Children from the rural schools had higher numbers of eggs in their
      faeces than those from the Serian schools. Children from the rural primary
      schools had higher number of eggs than those from the rural secondary school. The
      prevalence of Ascaris, Trichuris and hookworms in male and female and in primary
      and secondary school children was recorded.

PMID- 10972012
TI  - Multicentre study of preoxygenation practices by anaesthesia providers.
AB  - A total of 155 consecutive anaesthetics in three public Malaysian hospitals were
      prospectively studied to assess preoxygenation practices by their anaesthesia
      providers. Preoxygenation was practised in 96.1% of patients. Specialist and non
      specialist anaesthesiologist did not preoxygenate 8.8% and 2.3% of their
      patients, respectively. Overall incidence of arterial oxygen desaturation during
      induction was 15.5%. Arterial oxygen desaturation occurred more frequently with
      emergency surgery (30.2%) in comparison to elective surgery (9.8%). Arterial
      oxygen desaturation occurred more frequently with non-specialist (18.9%) than
      specialist anaesthesia providers (3.0%).

PMID- 10972013
TI  - Chronic HCV histology is predictable from HCV RNA and IgM anti HCV results.
AB  - The aim of this study was to determine if knowledge of both the serum HCV RNA and
      serum anti core IgM antibody status enabled one to predict the histological
      severity in chronic hepatitis C. We studied 45 female patients with chronic
      hepatitis C infection. The presence or absence of IgM antibodies to HCV and HCV
      RNA by PCR in each patient's serum was determined. Liver biopsies performed were
      scored according to a modified Desmet's histological activity index. Negative HCV
      RNA patients had least histological change. HCV RNA positive patients who were
      also IgM antibody positive had lower scores than their IgM negative counterparts.
      The grade of histological severity is more accurately predictable from knowledge
      of both the HCV RNA and IgM anti HCV status of the patient.

PMID- 10972014
TI  - Solitary focal coronary artery aneurysm in a middle aged male with atypical chest
      pain.
AB  - A 52 year old hypertensive Malay man, a smoker who presented with a one month
      history of mild chest discomfort not related to exertion and had a positive
      stress test with ST segment depression in the lateral leads. Coronary angiography
      showed stenosis in the right coronary artery and a coronary aneurysm in the
      proximal segment of his left anterior descending. The aneurysm was situated just
      distal to a stenotic lesion. The aneurysm is most likely related to
      atherosclerotic coronary artery disease. The patient was treated with oral
      nitrates, aspirin, angiotensin converting enzyme inhibitor and warfarin to
      prevent thromboembolism related to the coronary aneurysm. He remains asymptomatic
      one year after diagnosis.

PMID- 10972015
TI  - Ectopic pregnancy: uncommon presentations and difficulty in diagnosis.
AB  - Diagnosis of ectopic pregnancy prior to rupture is an arduous task even with the
      availability of many new investigative methods and imaging modalities. Above all,
      a high index of suspicion is necessary when dealing with women who present in
      early pregnancy with abdominal pain and vaginal bleeding. With the increased use
      of ovulation induction agents, the probability of heterotropic pregnancy should
      be kept in mind. The use of transvaginal ultrasonography (TVS) will help in
      earlier diagnosis because of its advantages over transabdominal ultrasonography
      (TAS).

PMID- 10972016
TI  - Disseminated histoplasmosis in a non-immunocompromised child.
AB  - We describe a 2 year-old non-immunocompromised girl with disseminated
      histoplasmosis who presented with a 2-month history of fever and bloody
      diarrhoea. On presentation, she was severely wasted and anaemic. There were gross
      hepatosplenomegaly and multiple lymphadenopathy. A septic screen was negative. A
      subsequent stool culture isolated Salmonella enteriditis. Serial Widal-Weil Felix
      (WWF) titres showed serological response after 2 weeks of Ceftriaxone. However,
      she continued to have spiking fever, bloody diarrhoea and weight loss. She
      developed pancytopaenia and disseminated intravascular coagulation. A bone marrow
      aspirate and trephine, and lymph node biopsy showed the presence of Histoplasma
      capsulatum, confirmed by Gomori-Methenamine Silver staining. She responded to
      intravenous amphotericin B followed by fluconazole (intravenous then oral) for 6
      months after discharge. Human Immunodeficiency Virus screening tests were
      negative. Complement and immunoglobulin levels were normal. T and B enumeration
      tests showed gross leucopaenia with very low T cell function with defective
      phagocytic function. A repeat T and B cell enumeration test and phagocytic
      function tests done 3 months later were normal.

PMID- 10972017
TI  - Airway stenting for tracheal stenosis.
AB  - Patients with upper airway obstruction from malignant disease are difficult to
      manage. A 62 year old patient presented with stridor and was found to have an
      upper tracheal tumour. Bronchoscopy, dilatation and stenting were performed
      successfully. The techniques and indications for the use of dynamic airway stent
      are discussed.

PMID- 10972018
TI  - Pattern of occupational allergic dermatitis in the Dermatology Clinic, Hospital
      Kuala Lumpur.
AB  - A two years retrospective analysis of patients diagnosed as contact allergic
      dermatitis with positive patch test attending the Dermatology clinic was
      performed. Of the 346 patients with a positive patch test, 14% had occupational
      dermatitis. This condition affected mainly young and inexperienced workers. An
      inverse relationship was seen between age and prevalence of occupational allergic
      dermatitis. Allergic hand dermatitis was the commonest presentation in
      occupational allergic dermatitis. This was followed by dermatitis of the exposed
      skin (face, neck, hands and forearms). The common sensitising agents identified
      were rubber chemicals and nickel. The two main groups at risk were factory
      workers and medical personnel. The common allergens found in factory workers were
      epoxy resin, pewter, nickel and rubber chemicals. Exposure dermatitis occurred in
      patients working in the pewter industry. Two thirds of medical personnel with
      hand dermatitis were allergic to rubber gloves. One year follow up after patch
      testing showed that 19% of patients still suffered from chronic dermatitis.
      Dermatitis improved in 34% of patients. Forty-seven percent were cured and
      stopped attending the clinic after patch testing and adequate counselling.

PMID- 10972019
TI  - New therapies for acute respiratory distress syndrome (ARDS):--a review.
AB  - Acute respiratory distress syndrome (ARDS) has been associated with high
      mortality. Improved understanding of the pathophysiology, recognition of
      precipitating events and improved management has decreased the mortality over the
      years. Mechanical ventilation is still the corner stone of the management of the
      disease. It is well recognised that high tidal volumes and airway pressures
      increase the morbidity, hence the need to use alternative modes of ventilation
      like pressure control with or without inverse ratio ventilation. Extracorporeal
      membrane oxygenation is still experimental and not easily available, whereas
      prone position to improve oxygenation is simple and inexpensive. The concept of
      pathological oxygen dependency and therapy aimed at supranormal values has failed
      to improve survival. Restricting the fluids to prevent further oedema formation
      in an already wet lung has improved the survival rate. Nitric oxide and
      surfactant have failed to produce desirable effect in large studies.
      Pharmacological support to inhibit inflammation with non steroidal anti
      inflammatory drugs, antifungal agents, prostaglandin and corticosteroids have all
      failed. Interestingly corticosteroid rescue treatment in the late phase of ARDS
      has shown promise. Antiendotoxin and anticytokine studies which began with much
      enthusiasm is yet to produce desirable results.

PMID- 10972020
TI  - Understanding the dental need and care during pregnancy: a review.
AB  - This paper reviews the oral and dental lesions that are seen during pregnancy.
      Trimester approach should be adopted in the management of the pregnant patients.
      A good dental preventive programme is essential. The significance of prescribing
      fluoride supplements and the use of dental radiography during pregnancy is also
      briefly reviewed.

PMID- 10972021
TI  - Hysterectomies in Malaysia: why are we left behind?

PMID- 10972022
TI  - A survey of hysterectomy patterns in Malaysia.

PMID- 10972023
TI  - Is snoring a health risk?

PMID- 10972024
TI  - Education of the public on cardio-pulmonary resuscitation: issues and challenges.

PMID- 10972025
TI  - The impact of teleradiology in clinical practice--a Malaysian perspective.
AB  - Teleradiology is the most mature and rapidly evolving specialty in telemedicine.
      The use of teleradiology has grown tremendously during the past few years. This
      article describes the role of teleradiology in health care along with a brief
      history of its development in tandem with advances in telecommunications and
      computer technologies. Teleradiology standards, image acquisition, data
      compression, transmission and image interpretation are summarised. The impact of
      teleradiology in the practice of radiology, traces the evolution of the modality
      especially in the Malaysian perspective and its current and future role are
      discussed.

PMID- 10972026
TI  - Treating high risk childhood solid tumours with autologous peripheral blood stem
      cell transplantation--early experience in University Hospital, Kuala Lumpur.
AB  - Although survival rates for childhood cancers have improved steadily over the
      past two decades, the outcome for advanced stage solid tumours remains poor. Many
      of these tumours are chemosensitive but most chemotherapeutic regimens are
      limited by their haematological toxicities. Much attention is now focused on mega
      dose chemotherapy followed by stem cell rescue in the treatment of disseminated
      neuroblastoma, rhabdomyosarcoma, germ cell tumour and brain tumours. There is a
      preferential shift towards peripheral blood stem cell transplantation instead of
      bone marrow transplantation because of its advantages of faster engraftment,
      decreased transfusion and antibiotic usage and shortened hospitalisation. This
      mode of therapy is dependent on technologies including peripheral blood stem cell
      harvesting, cell cryopreservation and thawing. These technologies were recently
      made available in Malaysia and we report our early experience.

PMID- 10972027
TI  - Bone mineral densities and hip axis lengths of normal Singapore women.
AB  - This study aims to evaluate the bone mineral densities and hip axis lengths of
      women in the local population. 227 normal Singapore women of ages 20 to 70 years
      had evaluation of their bone mineral densities (BMDs) by means of dual X-ray
      absorptiometry (DXA). The trend of BMDs at the left femoral neck and the lumbar
      spine remains fairly constant with increasing age until the 45-49 years age-band,
      beyond which there is a consistent decline. The mean hip axis length is 10.3 cm
      with a standard deviation of 0.6 cm. In general, the bone mineral densities in
      the femoral neck and lumbar spine as measured by DXA and the hip axis length of
      the local population is lower than corresponding figures reported in the Western
      population.

PMID- 10972028
TI  - X-ray based radiological procedures in Malaysia--1990-1994.
AB  - X-ray based radiological procedure statistics and trend in Malaysia for 1990-1994
      is reported; this information allows comparisons to be made with the United
      Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) Report.
      Additionally it is essential information for health care planners and providers.
      Malaysia is categorised as a health care level II country based on the UNSCEAR
      definition. In 1994, the number of physicians, radiologists, x-ray units and x
      ray examinations per 1000 population was 0.45, 0.005, 0.065 and 183 respectively.
      3.6 million x-ray examinations were performed in 1994, with chest radiography
      being the commonest study (63%). Information on x-ray examinations, number of
      hospitals and x-ray units is reported for the Ministry of Health, private
      practice and teaching hospitals. Examination frequency increased in computed
      tomography (161%), cardiac procedures (190%), and mammography (240%); while a
      decrease in barium studies (-23%), cholecystography (-36%), and intravenous
      urography (-51%) was noted. There is a potential and need to expand and upgrade
      radiological services.

PMID- 10972029
TI  - Medication noncompliance--a thriving problem.
AB  - A study was conducted among out-patients attending the Melaka Tengah Health
      Clinic to determine their compliance status towards antihypertensive,
      antidiabetic and antiasthmatic drugs. A total of 585 patients were enrolled in
      this study. Assessment of compliance was carried out using pill-counting and
      house-to-house interviews 14 days from the date of medication dispensed at the
      counter. The noncompliance rate among the 464 successfully interviewed patients
      was 56%. The mean noncompliance percentage was 78.0 +/- 43.1% (range: -10.0
      314.3%). Among the four variables of compliance studied, race was not seen as a
      determinant of compliance. The older age group and those taking two or more drugs
      were statistically significant to be a noncomplier. Females were highly likely
      not to comply with drug therapy. Patients who conform to their refill dates were
      not really drug compliers. Forgetting to take their drugs and inability to read
      instructions on drug labels were the main reasons given. Underdosing was more
      common than overdosing, with an estimated cost of RM20,261.00 of unused
      medications per year.

PMID- 10972030
TI  - [Seasonal migration: a case control study of malaria prevention in Sabah].
AB  - Malaria is an infectious disease that remains the main health problem in Tawau,
      Sabah. A case control study was carried out in the district to determine the
      influence of seasonal migration on malaria occurrence. Respondents consisted of
      142 cases who were randomly selected from the reported cases in 1996 and they
      were pair-matched with 142 controls from the same villages by age and sex. The
      results showed that malaria occurrence was significantly associated with movement
      to the jungle, use of preventive measures during migration and frequency of using
      treated bednets (p < 0.05). The risk of individuals migrated to the jungle was 6
      times as compared to those who do not (unadjusted Odd Ratio = 5.50, 95% CI 1.16
      35.89) and they were more likely to get the infection if they did not use bednets
      (OR = 3.57, 95% CI 1.57-9.06). Health promotion campaign on the use of bednets
      especially during short term migration should be given priority in any malarial
      intervention program.

PMID- 10972031
TI  - Radiation therapy in skeletal metastases.
AB  - From June 1993 to September 1995, 132 case files of patients who received
      palliative radiotherapy (RT) for skeletal metastases were reviewed. Majority of
      the patients (75/132) was in the age range of 41-60 years. Common sites of
      metastases were the vertebrae (86 patients) and the pelvic bones (40 patients).
      The major primary tumors encountered were as follows: multiple myeloma (30),
      breast cancer (25) and prostate cancer (20). Pain was the commonest symptom of
      presentation. Doses of palliative RT ranged from 8-40 Gy in different
      fractionation schedules. Ninety-four patients showed more than 50% symptomatic
      response, 26 had no response and 12 were lost to follow up immediately after the
      treatment. Single fraction treatments resulted in almost similar responses
      compared to various multiple fraction treatments. To conclude, short course
      radiation therapy regimes are optimum in our local circumstances where RT
      resources are limited and patients have to travel long distances to attend
      hospital.

PMID- 10972032
TI  - Common anxieties of patients undergoing oesophago-gastro-duodenoscopy,
      colonoscopy and endoscopic retrograde cholangio-pancreatography.
AB  - AIMS & METHODS: To investigate the anxieties of patients undergoing oesophago
      gastro-duodenoscopy (OGD), colonoscopy and endoscopic retrograde cholangio
      pancreatography (ERCP) in relation to their demographic features, their knowledge
      and understanding of the procedure, its indication, and their doctors'
      explanation. A standard questionnaire was filled in consecutively for 280 OGD
      patients, 64 colonoscopy patients and 50 ERCP patients. RESULTS & CONCLUSIONS:
      Majority of the anxious patients were afraid of pain. There was no difference
      between the "fearless" and "fearful" groups in terms of source of referral and
      inpatient/outpatient status. However for all 3 procedures, anxious patients were
      significantly younger by a mean of 10 years. Females, better educated and OGD
      patients undergoing the procedure for the first time were more anxious but this
      difference was not seen with the more complex colonoscopy and ERCP. The more
      sophisticated ERCP seemed to instill greater anxiety amongst Malay patients.
      Doctors were significantly more likely to explain the indication for OGD and
      colonoscopy than how it would be done. This discrepancy was not seen with ERCP
      where the endoscopists tend to adopt a more personal approach. Most patients
      prefer to be sedated.

PMID- 10972033
TI  - Acute respiratory distress syndrome in a paediatric intensive care unit.
AB  - Acute respiratory distress syndrome (ARDS) is the final outcome of a common
      pathway of a variety of unrelated but massive insults to the lung. It is commonly
      seen in adults but also occurs in the paediatric age group. A prospective study
      was carried out to determine the incidence, predisposing conditions, clinical
      course and outcome of children with ARDS admitted to a paediatric intensive care
      unit (PICU). Six patients (aged 0.8 to 11 years) who fulfilled the strict
      criteria for ARDS were identified prospectively during a one year study period.
      The incidence was 1.7% of all PICU admission. The most common underlying
      conditions were septicemia and pneumonia. The mortality rate was 83%. Death most
      often occurred during the early phase of the disease. Treatment of ARDS included
      elimination of the cause of ARDS, early institution of mechanical ventilation
      with PEEP, prompt recognition and treatment of superimposed infection and careful
      management of additional organ failure.

PMID- 10972034
TI  - Caecal diverticulitis--a review of eight cases in Taiping, Malaysia.
AB  - Most patients presenting with acute right sided peritonitic pain are diagnosed
      and managed as acute appendicitis. In a series of 336 patients, eight were found
      to have caecal diverticulitis. The occurrence of such diverticula appears to be
      more frequent in Asian populations. The diagnosis can be established at operation
      on the basis of surgical findings. The aim of this retrospective review is to
      discuss the management of such patients when acute diverticulitis is found at the
      time of appendicectomy. It is advocated that management be conservative where
      possible, with appendicectomy and antibiotics. Where the possibility of a
      carcinoma remains, investigation after surgery by colonoscopy may be undertaken.

PMID- 10972035
TI  - Characteristics of acute pancreatitis in University Kebangsaan Malaysia.
AB  - We analyzed the characteristics of patients presenting with acute pancreatitis to
      our unit. A total of 71 patients were admitted to the Surgical Department at
      University Kebangsaan Malaysia (UKM) over a period of seven years, between
      January 1990 to December 1996 with acute pancreatitis. There was a fourfold
      increase in incidence of acute pancreatitis in our hospital from January 1990 to
      December 1996. The commonest identifiable aetiology was gallstones followed by
      alcohol. There were two deaths. We conclude that acute pancreatitis is
      increasingly being diagnosed in our local population. This may be due to either
      greater awareness or changes in lifestyle of the population.

PMID- 10972036
TI  - Colonization and transmission of Ureaplasma urealyticum and Mycoplasma hominis
      from mothers to full and preterm babies by normal vaginal delivery.
AB  - A prospective study was carried out among pregnant women and their newborn babies
      in the University Hospital, Kuala Lumpur from January 1996 to June 1997. The
      maternal cervical colonization rates of Ureaplasma urealyticum (UU) and
      Mycoplasma hominis (MH) were found to be 57.5% and 15.8% respectively while the
      isolation rates from nasopharyngeal secretions of the newborns were 50.8% for UU
      and 6.6% for MH. The overall transmission rates were 88.4% for UU and 42.1% for
      MH. There was no significant difference in the transmission rates of either
      organism from mothers to their respective newborn babies by the maturity of
      pregnancy. In preterm babies, the nasopharyngeal isolation rates of UU and MH
      were not influenced by the babies' gestational age and birth weight nor by the
      maternal history of abortion or parity. However, there was a tendency for UU to
      persist in the nasopharyngeal secretion of preterm babies especially those of
      birth weight below 2 kg. None of the babies contaminated with mycoplasmas at
      birth developed respiratory symptoms during six to eight weeks of follow-up.

PMID- 10972037
TI  - Work related upper limb disorders in telecommunication workers in Malaysia.
AB  - A total of 323 workers from 5 different occupational groups in the
      telecommunication industry were studied in this cross sectional study, which
      sought to determine the prevalence of Work Related Upper Limb Disorders (WRULD)
      in 5 occupational groups; operators using the Video Display Terminals,
      switchboard operators, clerks, data entry processors and the supervisors. WRULD
      was also studied with regard to factors such as sex, race, height, age, stress
      and the discomfort perceived due to the work station design. The possibility of
      WRULD was determined from a self-administered questionnaire and confirmed by
      history and physical examination. Psychological stress and the discomfort due to
      the workstation were measured from the questionnaire. The overall prevalence was
      found to be 31.2% and the prevalence among the various occupations differed with
      it being the highest in the switchboard operators and data processors and the
      lowest in the supervisors. The older workers and the female workers were found to
      have higher prevalences of WRULD. It was also found that a higher stress score
      and a higher score of discomfort perceived at the work station were associated
      with higher prevalences of WRULD.

PMID- 10972038
TI  - Mass cardio-pulmonary resuscitation: a new method of public cardio-pulmonary
      resuscitation teaching.
AB  - A mass CPR (cardio-pulmonary resuscitation) teaching programme, believed to be
      the first in Malaysia, was held at the Dewan Tunku Canselor, University of Malaya
      (UM) on Saturday, 13th July 1996. Organised by the Resuscitation Committee of
      University Hospital, Kuala Lumpur, this programme was conducted for 200 first
      year UM students. We describe the organisation of this non-traditional and non
      threatening, new CPR teaching programme and propose that this be further
      developed for the dissemination of CPR skills to our Malaysian public.

PMID- 10972039
TI  - Osteosarcoma in a sixteen-month old boy.
AB  - We report a case of a sixteen-month old boy with osteosarcoma of the left
      humerus. To the best of our knowledge this is the youngest case reported in
      Malaysia. This case illustrates that osteosarcoma although rare does occur in a
      very young child. The child died six weeks after presentation due to disseminated
      disease.

PMID- 10972040
TI  - Penicillium marneffei infection in a non aids patient: first case report from
      Malaysia.
AB  - Penicillium marneffei, a dimorphic fungus is a rare opportunistic pathogen. It is
      known to cause infection in immunocompromised patients and recently its
      occurrence in AIDS patients has been well-documented. Disease with Penicillium
      marneffei is even rarer among previously healthy individuals. The disease is
      endemic in Southeast Asia and China. Recognition of this rare disease is
      important because it is amenable to treatment. We report a case of P. marneffei
      infection in a previously healthy individual.

PMID- 10972041
TI  - Duodenal obstruction secondary to metastatic synovial sarcoma--a case report.
AB  - A 17 year old Malay student who is a known case of synovial sarcoma of left elbow
      (treated with an above elbow amputation) presented with duodenal obstruction. We
      report an unusual case of gastrointestinal tract metastases from synovial
      sarcoma. To our knowledge, there is no previous such report in the literature.
      The computed tomography (CT) and magnetic resonance imaging (MRI) features are
      described.

PMID- 10972042
TI  - Adult varicella pneumonia that responded to combined acyclovir and steroid
      therapy.
AB  - We describe a case of adult chickenpox which was complicated by severe varicella
      pneumonia, mild hepatitis and thrombocytopenia. The hepatitis and the
      thrombocytopenia were asymptomatic clinically and were diagnosed on biochemistry
      and blood count results. These eventually improved without specific
      interventions. The pneumonia, however, deteriorated rapidly despite the early
      commencement of oxygen supplementation, acyclovir and antibiotic. Subsequently,
      systemic corticosteroid therapy was initiated and the patient was ventilated in
      the intensive care unit. The patient eventually recovered.

PMID- 10972043
TI  - A case report: intracranial haemorrhage in a patient with probable dengue fever.
AB  - We present a rare case of a patient diagnosed with probable dengue fever
      sustaining an intracranial haemorrhage after a trivial motor vehicle accident.
      From the literature reviewed, it was noted that there have been no reports of
      dengue fever presenting with an intracranial haemorrhage, and the association is
      more common in patients diagnosed with dengue hemorrhagic fever and/or dengue
      shock syndrome.

PMID- 10972044
TI  - Radical resection for naso-lacrimal duct tumour.
AB  - Naso-lacrimal duct tumours are uncommon and present with epiphora and swelling.
      Since the naso-lacrimal duct is embedded in bone for the majority of its
      anatomical length, the late presentation of proptosis is due to orbital extension
      of the tumour. Radical surgical treatment is necessary to establish clear margins
      and facilitate reconstruction.

PMID- 10972045
TI  - Endometrial carcinoma can develop in patients on tamoxifen therapy.

PMID- 10972046
TI  - High white cell count at presentation in children with acute lymphoblastic
      leukaemia.

PMID- 10972047
TI  - Organ donation: a case for a "presumed consent" law in Malaysia?

PMID- 10972048
TI  - Emerging and re-emerging infections.
AB  - An emerging infection is defined as an infection which has newly appeared in a
      population while a re-emerging infection is one which has existed in the past but
      its incidence is rapidly increasing. The reasons for the emergence and re
      emergence of infections are not well understood but appear to be associated with
      factors that involve the pathogen, the host and the environment. These factors
      are often inter-related and act together in a complex manner to bring about
      changes in patterns of infection. Pathogens are extremely resourceful and possess
      mechanisms to adapt to new hosts and environments as well as to acquire new
      virulence traits. Host factors include herd immunity, social behaviour and
      demographics. Environmental factors like the climate, deforestation and new
      technologies have an impact on the emergence of infections. The challenge is to
      contain an infection when it emerges but more importantly to prevent its
      emergence in the first place. As the emergence of an infection is complex and
      multifactorial, a multidisciplinary approach is required. Health based strategies
      alone are insufficient. Social, economic and environmental measures and the
      political will to implement appropriate policies are equally important.

PMID- 10972049
TI  - [Reflex sympathetic dystrophy vs. a factitious disorder].
AB  - Three women aged 18, 30 and 21, were admitted with complaints of reflex
      sympathetic dystrophy. These patients were caught at inducing their symptoms.
      Factitious disorders may be more common and serious than expected. It is
      suggested to include this diagnosis routinely in the differential diagnosis when
      dealing with inexplicable complaints, symptoms or therapy resistance. If
      factitious disorders are diagnosed it is advised to confront the patients. This
      is important in order to limit further iatrogenic damage to the patient. It also
      allows the physician to inform other doctors. After confrontation quite a few
      patients will stop inducing their symptoms. Most of them become angry, deny self
      induction and refuse psychiatric help. Sometimes patients will withdraw from
      treatment. Despite these negative reactions patient confrontation is mandatory.

PMID- 10972050
TI  - [Treatment of posttraumatic dystrophy].
AB  - Reflex sympathetic dystrophy, posttraumatic dystrophy or complex regional pain
      syndrome is a particular type of chronic pain. Although the origin is unknown,
      some believe that wide-dynamic range neurons located in the dorsal horn of the
      spinal cord play an essential role. Others consider the role of psychogenic
      factors underestimated. Until now, controlled clinical trials mainly directed at
      modulation of the sympathetic system have not revealed clearly effective
      therapies. Tests with guanethidine, phenylephrine, phentolamine or lidocaine have
      essentially been negative. Use of low dose glucocorticoids, dimethylsulphoxide,
      biphosphonates and epidurally applied clonidine require confirmation in studies
      of larger size. There are indications that invasive electrical spinal cord
      stimulation may have some effect; randomized studies in patients with
      posttraumatic dystrophy are needed. So far, only application of physical therapy
      at an early stage has clearly shown effective pain relief and would also lead to
      cost reduction.

PMID- 10972051
TI  - [Diagnosis and therapy of patients with euthyroid goiter].
AB  - Nontoxic goitre is common, even in areas where iodine intake is sufficient. The
      most important symptoms and signs of nontoxic goitre are caused by compression of
      vital structures in the neck or upper thoracic cavity. In any patient with goitre
      the serum concentration of thyroid-stimulating hormone (TSH) should be measured
      to detect or exclude clinically inapparent (subclinical) hyper- or
      hypothyroidism. CT and MRI are expensive but very sensitive methods to identify
      tracheal compression and to determine intrathoracic extension. Thyroid
      ultrasonography and scintigraphy are not routinely indicated. Fine-needle
      aspiration biopsy is indicated in patients with fast-growing nodules and nodules
      that have a firmer consistency than other nodules within the gland. Thyroidectomy
      is standard therapy for young and otherwise healthy patients, especially when
      prompt decompression of vital structures is required. Radioiodine therapy is an
      attractive alternative to surgery in older patients, in those with
      cardiopulmonary disease, and in those with recurrent goitre. Thyroxin therapy may
      be tried in young patients with small, diffuse goitres who have normal serum TSH
      concentrations.

PMID- 10972052
TI  - [Atypical antipsychotic drugs].
AB  - In recent years several new antipsychotics have come to market in the Netherlands
      (i.e. risperidone, olanzapine and quetiapine). These compounds are called
      atypical for their lack of the extrapyramidal side effects typical of older
      antipsychotics. Clozapine, which was developed earlier, is also an atypical
      antipsychotic drug. The new antipsychotics have proven to be more effective than
      the old ones in reducing the negative symptoms and in improving the cognitive
      deficits of schizophrenia. Moreover, they indeed induce less extrapyramidal side
      effects than the older antipsychotics. Head-to-head comparisons of the atypical
      antipsychotics are sparse. Studies comparing low-dose regimens of the typical
      antipsychotics with the atypical drugs as well as relapse prevention studies are
      needed before it can be decided whether the atypical drugs can replace the older
      compounds.

PMID- 10972053
TI  - [Primary osteomyelitis of sternum].
AB  - Primary osteomyelitis of the sternum is rare, especially in young adults. A 16
      year-old boy was admitted to the orthopaedic department with chest pain and
      fever. The blood culture was positive for Staphylococcus aureus. MRI revealed a
      retrosternal abcess; a bone scan showed increased local uptake, suggestive of
      isolated osteomyelitis. Two weeks after the start of treatment with
      flucloxacillin 1 g 6 times a day i.v. the patient's condition had significantly
      improved: the pain had subsided and the fever had disappeared. In sternal
      osteomyelitis early treatment with antibiotics is successful and avoids
      complications and surgical intervention.

PMID- 10972054
TI  - [Driving ban for patients on chronic opioid therapy unfounded].
AB  - Dutch law states that persons who are on treatment with morphine preparations,
      even if these are slow-release drugs, are unfit to drive a motor vehicle. There
      is no scientific basis for such a measure, however. On the contrary, current
      evidence indicates that e.g. cancer patients using 209 mg morphine daily for
      three months do not differ significantly from a control group with respect to
      thinking abilities, alertness, concentration, reaction speed and dividing
      attention. For obvious reasons utmost care must be observed with the use of
      morphine by traffic participants. But a rigorous prohibition of driving for
      patients requiring chronic alleviation of severe pain needlessly restricts their
      mobility.

PMID- 10972055
TI  - [CBO guideline 'Stroke' (revision)].

PMID- 10972056
TI  - [Fifty years of plastic surgery in the Netherlands. VII. Hand surgery].

PMID- 10972057
TI  - [Total proctocolectomy with ileo-anal reservoir in "J". Experience at the
      Salvador Zubiran National Institute of Nutrition].
AB  - BACKGROUND: Total proctocolectomy with ileal pouch-anal anastomosis (TPCIAA) is
      the procedure of choice for patients with Ulcerative Colitis and Familial
      Adenomatous Polyposis. The frequency of presentation of both diseases is low in
      Mexico, therefore the experience with the surgical procedure is limited.
      OBJECTIVE: To analyze the operative morbidity and mortality and long-term
      functional results in a series of patients operated upon with the TPCIAA in a
      referral center in Mexico. MATERIAL AND METHODS: Retrospective analysis of 44
      consecutive patients operated upon from 1987 through 1997. The operation included
      resection of the anal transitional zone, handsewn anastomosis of a "J" pouch, and
      diverting ileostomy in all cases. Operative morbidity and mortality, and long
      term functional results and complications were determined. RESULTS: Mean age was
      33 +/- 15 years. There were 52% women and 48% men. Diagnoses were ulcerative
      colitis in 59% and familial polyposis in 36%. Global morbidity was 39%, and
      mortality 2%. With a mean follow-up of 24 months, mean number of bowel movements
      was 4, 10% of patients had diurnal spotting, 30% nocturnal spotting, and no
      patient had gross incontinence. Three patients presented pouchitis with adequate
      response to antibiotics. Two patients presented long-term pouch fistulas that did
      not require pouch excision. CONCLUSIONS: The TPCIAA is a feasible operation with
      acceptable rates of morbidity and mortality and satisfactory functional results.

PMID- 10972058
TI  - Accuracy of combined clinical findings and fine needle aspiration cytology for
      the diagnosis in palpable breast tumors.
AB  - OBJECTIVE: A prospective study to evaluate the confidence level and predictive
      value of the fine needle aspiration biopsy was performed in the Oncology Service,
      "Hospital 20 de Noviembre, ISSSTE", Mexico City. MATERIAL AND METHODS: The cases
      with a palpable breast tumor, histologically confirmed who presented from 1992 to
      1994 were included. One aspirate was done in each patient and these were reviewed
      by the same pathologist. We determined sensitivity, specificity and predictive
      value of the test. Age, border characteristics, size and mobility of the tumor
      were evaluated by Bayesian analysis. RESULTS: From 213 aspirates, 199 were
      elegible for diagnosis, 98 (46%) had a diagnosis of carcinoma, 13 were acellular
      and one suggestive. The acellular diagnoses were considered negative and
      suggestive positive, for analysis purposes. Mean age and tumor size were: 46.6
      years (range 14-90) and 3.7 cm. (range 1-13) respectively. Sensitivity (0.932),
      specificity (0.973) and positive predictive value (96.9%) were estimated. We
      observed a high probability of true positive [P(D+/T+)] > 0.8 results in patients
      between 40 and 60 years of age, irregular borders, size > 2 cm and fixed lesions.
      CONCLUSIONS: The test has a high confidence level and in presence of two or more
      of the clinical factors mentioned, definitive decisions regarding treatment could
      be taken, without need of histologic confirmation.

PMID- 10972059
TI  - Exophthalmometry in Mexican adults.
AB  - BACKGROUND: Up to the present time we do not know of any report about normal
      proptosis values in normal Mexican adults. Moreover, we think it is important to
      establish them in each population to distinguish between normal and pathological
      orbital processes because the values may vary in relation to ethnic factors.
      SUBJECTS AND METHODS: Ocular protrussion values using Hertel's exophthalmometer
      were measured in 301 randomly selected normal adult subjects (185 females and 116
      males), mean age 36 +/- 8.6 years, without known history of ocular trauma,
      surgery, endocrine disease or any ocular pathologic process. RESULTS: The mean
      protrussion value was 15.18 +/- 2.16 mm for males and 14.82 +/- 1.98 mm for
      females. (p = NS). The distance between the lateral orbital rims was 97.78 +/-
      3.97 mm for males and 94.33 +/- 1.98 mm for females (p < 0.001). We found a
      statistically significant difference between the values found in Mexican adults
      and those of American white and black subjects with enough data to make
      statistical calculations. DISCUSSION: We established normal proptosis values for
      Mexican adults using Hertel's exophthalmometer. Ocular protrussion was lower than
      those reported in normal American black and white adults. We argue that the
      differences may be explained by different skull structure, and more specifically,
      orbital due to anthropological or racial differences.

PMID- 10972061
TI  - [Comparison of 2 educational interventions in the training of resident
      physicians].
AB  - OBJECTIVE: To compare the results of two educational interventions, habitual
      versus experimental, in a group of pediatric residents. METHODS: We evaluated 7
      residents in the last 4 months of their first year training by incorporating
      additional hours of an Experimental Intervention (EI) to their Habitual Training
      (HT). During EI we forced group discussion and debate in the classroom activities
      in contrast with the HT which was a passive approach of lectures with little or
      no participation by the trainees. We used a previously developed Differential
      Scale of a Group Interaction (DSGI) to score groupal activities conducive to
      better learning during EI and HT at 1, 6 and 11 weeks of starting EI.
      Simultaneously, the individual participations were scored with an Observation
      Guide of Discussion and Debate (OGDD) but only during EI as it would score near
      zero during HT. RESULTS: The DSGI scores were significantly and increasingly
      higher during EI than during HI at 1, 6 and 11 weeks of EI. All trainees improved
      their OGDD score after 6 and 11 weeks of EI. CONCLUSIONS: The educational
      microenvironment created by the Experimental Intervention improved the knowledge
      and aptitudes for discussion and debate of the trainees. Their increased use of
      critical exchanges and confrontations of ideas contributed to a better
      construction of their knowledge as pediatric residents.

PMID- 10972063
TI  - [Collapsing glomerulopathy: a new entity associated with nephrotic syndrome and
      end-stage renal failure].
AB  - Collapsing glomerulopathy is an aggressive form of glomerular disease defined for
      its histopathological features of glomerular collapse, visceral epithelial cell
      damage and tubulointerstitial changes that are characteristic. Patients with
      collapsing glomerulopathy present with severe nephrotic syndrome, marked
      proteinuria, generally more than 10 g/day and rapid progression to chronic renal
      failure, or death due to complications of nephrotic syndrome, despite any form of
      treatment. Collapsing glomerulopathy presents as de novo or recurrent disease in
      the renal allograft. There is slight predominance in males and strong
      predominance in blacks as renal diseases in general. Collapsing glomerulopathy
      shares several clinical and histopathological features with focal and segmental
      glomerulosclerosis and HIV-nephropathy; nevertheless, there is enough evidence to
      support collapsing glomerulopathy as a different entity. It must be mentioned
      that collapsing glomerulopathy, focal and segmental glomerulosclerosis and HIV
      nephropathy may have a similar pathophysiological mechanism of damage to the
      visceral epithelial cell.

PMID- 10972062
TI  - Multiple recurring paragangliomas: a problem of diagnosis and location. Case
      report and review of the literature.
AB  - RATIONALE: Paragangliomas constitute a particular diagnostic challenge because of
      the difficulties involved in identifying new lesions. CASE REPORT: The findings
      in the case of a young woman with multiple recurring paragangliomas which
      reappeared eleven years after successful surgical treatment are presented.
      DISCUSSION: This case illustrates the diagnostic difficulties of this pathologic
      entity and the lack of a technique of sufficient sensitivity to reveal the
      existence of one or more tumors with or without hormonal secretion, their
      location and rate of growth and the number of neoplasias to avoid as many
      surgical interventions as possible. Inasmuch as an ideal technique for diagnosis
      and localization of this type of tumor remains to be developed, non-invasive
      methods, particularly 131I MIBG scintigraphy, play a significant role in
      evaluation because of their high sensitivity for detecting chromaffin tissue,
      especially in extra-adrenal locations. CONCLUSION: Periodic long-term
      radionuclide scanning should be recommended for all asymptomatic patients given
      the risk of residual and/or reactivating tumoral tissue with benign or metastatic
      behavior.

PMID- 10972060
TI  - [Prospective evaluation of gastroesophageal reflux in patients with achalasia
      treated with pneumatic dilatation, thoracic or abdominal myotomy].
AB  - INTRODUCTION: Symptomatic gastroesophageal reflux (GER) occurs in 0-20% of
      patients treated with pneumatic dilation and in 5-30% with cardiomyotomy.
      However, the prevalence of GER evaluated with esophageal pH-monitoring is
      unknown. AIM: To investigate the frequency of GER in achalasia patients treated
      with pneumatic dilation or myotomy. MATERIAL AND METHODS: Patients with achalasia
      were evaluated prospectively and classified in 4 groups: group A = treated with
      pneumatic dilation; group B = treated with open abdominal myotomy; group C =
      transthoracic myotomy; and group D = submitted to laparoscopic abdominal myotomy
      with antireflux procedure. Esophageal manometry and 24 h pH-monitoring were
      performed in all patients. GER was defined as a pH < 4 in more than 4% of the
      total time. RESULTS: Thirty-one patients, 22 women and 9 men, with a mean age of
      44.7 years were evaluated. Nine patients had GER symptoms and 22 were
      asymptomatic. GER was detected with pH-metry in 42% of the total group: 33% for
      group A, 75% for group B, 44% for group C and none for group D. CONCLUSIONS:
      Prevalence of GER in achalasia patients treated with pneumatic dilation and
      surgical myotomy was high. We suggest the inclusion of 24 hr esophageal pH-metry
      in the follow-up due to the significant prevalence of asymptomatic GER. Minimal
      hiatus dissection and antireflux procedure were surgical factors related with a
      lower frequency of GER after achalasia myotomy.

PMID- 10972065
TI  - [In Process Citation]

PMID- 10972064
TI  - [Genetic transcription in eukaryotes: from transcriptional factors to disease].
AB  - The organisms' genetic information is stored as DNA sequences: the genes. The
      most important level of gene expression regulation is exerted at the transfer
      process of this information from the genes into messenger RNA molecules; this
      process is called transcription and is carried out by a molecular machinery
      conformed by hundreds of different proteins which are assembled in an ordered
      step way. These proteins or transcriptional factors are classified according to
      their mode of action in 4 groups: general transcriptional factors, activators,
      coactivators and repressors. There are diseases like. Aniridia, the Rubinstein
      Taybi syndrome and Hodgkin's disease, in which some transcriptional factor have
      been involved and in some, the molecular cause i.e. the mutations responsible for
      the molecular dysfunction in a transcriptional factor has been elucidated.
      Understanding at the molecular level the transcription process will help to
      comprehend the relationship of it with the development and health of the
      organism.

PMID- 10972066
TI  - [Left ventricular assistance: an answer to terminal cardiac failure?].

PMID- 10972067
TI  - [Is clinical research scientific? Karl Popper and clinical research].

PMID- 10972069
TI  - [Cutaneous drug reactions: diagnosis and etiology].
AB  - Drug eruptions are frequently encountered in clinical practice. Their great
      variety raise many problems and their complete knowledge is actually impossible.
      A logical approach is to describe the dermatological signs and the associated
      signs and symptoms. All the drugs taken by the patient and the dates of doses
      must be referred. Secondly, more informations may be obtained thanks to the
      dermatologist or a Drug Alert Registry (Regional Center of Pharmacovigilance in
      France). Bibliographical data varied in quality; the Vidal dictionary is often
      used, but Internet may be questioned. Imputability methods are well developped in
      France. In vivo and in vitro methods do not offer sufficient sensibility and
      specificity.

PMID- 10972068
TI  - [Mechanisms of cutaneous drug reactions].
AB  - Two main mechanisms, pharmacologic and immunoallergic, are responsible for
      cutaneous reactions to drugs. Pharmacologic mechanisms can be predictable
      (overdosage, cumulative or delayed toxicity, adverse effects) or unpredictable
      (idiosyncratic, intolerance, or anaphylactic reaction). Immunoallergic mechanisms
      can be mediated by IgE (some types of urticaria and anaphylactic shock), due to
      circulating immune complexes (leukocytoclastic vasculitis, serum sickness-type
      reactions) or mediated by lymphocytes (exanthema, Lyell's syndrome, fixed
      pigmented erythema, photosensitization). The diagnostic work-up varies according
      to the causative mechanism. When the reaction is predictable, the responsible
      drug can be identified according to the data in the present bibliography. When
      the reaction is immunologic, only the chronologic sequence of events can identify
      the responsible drug. The risk of recurrence with an identical or related
      molecule also varies according to the causative mechanism. For urticaria,
      diagnosis and the risk of recurrence differ according to whether the cause is
      allergic (mediated by IgE or urticarial vasculitis) or is pharmacologic
      (urticaria due to aspirin or to conversion enzyme inhibitors).

PMID- 10972070
TI  - [Drug-induced urticaria].
AB  - According to different estimations, the systemic or topical administration of
      drugs is the 2nd or 3rd identified cause of urticarias. Urticaria may be the
      leading symptom of drug-induced immuno-allergic reactions such as anaphylaxis or
      serum sickness. More often, it is the manifestation of non-immune reactions by
      drug-induced direct release of histamine, activation of complement or enzymatic
      impairment of the metabolism of arachidonic acid derivatives. Skin tests may be
      helpful for the demonstration of the responsibility of drugs in the immuno
      allergic reactions. Whatever the mechanism may be, one should dissuade from
      provocation reintroduction of the suspected drug without an extreme wariness.

PMID- 10972071
TI  - [Drug-induced exanthemas].
AB  - Drug-induced exanthemas are probably the most frequent cutaneous adverse drug
      reaction. Outcome of the isolated forms are usually favourable. However,
      exanthemas may be part of a more severe form, as hypersensitivity syndrome, Lyell
      syndrome, Stevens-Johnson syndrome or acute generalized exanthematic pustulosis.
      The mechanism is essentially immunologic. Antibiotics (aminopenicillins,
      antibacterial sulfamides, antituberculosis drugs) must be considered high risk
      drugs. Treatment is only symptomatic. Corticosteroids must be avoided.

PMID- 10972073
TI  - [Blistering drug reactions].
AB  - The occurrence of erosions on the mucous membranes and (or) blisters on the skin
      usually indicates the seriousness of an adverse drug reaction. This paper will
      review the clinical and histological presentation, drug causes, and prognosis of
      blistering drug eruptions, with special focus on the most severe: Stevens-Johnson
      syndrome and Toxic epidermal necrolysis.

PMID- 10972072
TI  - [Drug-induced photosensitivity].
AB  - Photodermatosis are dermatoses where there is an abnormally exaggerated
      sensitivity to sunlight, termed photosensitivity, that is often drug-induced.
      Such drug-induced photosensitivity is due to the mechanism of
      photosensitivization that induces two types of reaction, phototoxic and
      photoallergic. The phototoxic reaction is photochemical, irritative and common,
      and can occur in any individual without any particular predisposition. The
      photoallergic reaction is a photoimmunologic, cell-mediated hypersensitivity
      reaction. It is much more rare and occurs only in some individuals with
      predisposition. Clinically, the phototoxic reaction usually manifests by a
      cutaneous "sunburn" type eruption, and the photoallergic reaction by eczema.
      Photosensitizing drugs are numerous: antibiotics, nonsteroid anti-inflammatory
      drugs, diuretics, antimitotic drugs, psychiatric drugs, amiodarone, calcium
      channel blockers, fibric acid derivatives, etc. Diagnosis is based on recognition
      of an eruption localized in zones exposed to sunlight occurring in the context of
      photosensitizing drug intake, correlated with the results of photobiological
      laboratory investigations.

PMID- 10972074
TI  - [Cutaneous reactions to topical medications].
AB  - The management of patients who have developed a contact dermatitis due to topical
      drugs requires to stop the suspected drug application, to declare, if serious,
      the adverse drug reaction to the Pharmacovigilance network, to treat the patient
      with corticosteroid ointments, to perform dermatoallergological investigations
      e.g. drug patch tests to determine whether the adverse reaction was due to
      excipients or to the drug itself and at least to advise the patient concerning
      the avoidance of topical or systemic readministrations of the responsible
      molecule. An excipient responsible in inducing a contact sensitisation to an
      ointment can also be found in cosmetics. When a drug is responsible it is
      necessary to determine if cross-reactions with other drugs can occur and if the
      responsible molecule can induce systemic cutaneous adverse reaction if the drug
      is systemically readministered.

PMID- 10972075
TI  - [Misleading or rare cutaneous drug reactions].
AB  - Drug hypersensitivity syndrome and drug-induced cutaneous pseudolymphoma were for
      a long time considered as one and the same. Today, however, two clinical entities
      have been distinguished; the former is responsible for a mortality rate estimated
      at 10% whereas the prognosis of the latter is always excellent. Acute generalized
      exanthematous pustulosis is a rare drug eruption individualised in 1980. Numerous
      drugs can induce acneiform eruptions or trigger or even worsen an authentic acne.
      The number of drugs responsible for buccal mucous membrane involvement is on the
      increase; gingival hypertrophy remains a rare drug reaction, a certain number of
      drugs such as nicorandil can cause buccal aphtae and even giant ones.

PMID- 10972076
TI  - [In Process Citation]

PMID- 10972077
TI  - [Atherosclerotic obstruction of the aorta and lower limb originating from an
      atheroma. Diagnosis, evolution].

PMID- 10972078
TI  - [Atopic dermatitis. Diagnosis, evolution, treatment].

PMID- 10972079
TI  - [CMV infection in a patient with HIV. Diagnosis, evolution, principles of
      treatment].

PMID- 10972080
TI  - [Neonatal jaundice. Physiopathology, etiology, diagnosis].

PMID- 10972081
TI  - [The elderly. Demography, economic and social aid, health and social services].

PMID- 10972082
TI  - [Urinary infections in pregnancy. Diagnosis, development, treatment].

PMID- 10972083
TI  - [Proteinuria. Diagnostic approach].

PMID- 10972084
TI  - Cancer-induced defective cytotoxic T lymphocyte effector function: another
      mechanism how antigenic tumors escape immune-mediated killing.
AB  - BACKGROUND: The notion that a deficit in immune cell functions permits tumor
      growth has received experimental support with the discovery of several different
      biochemical defects in T lymphocytes that infiltrate cancers. Decreased levels of
      enzymes involved with T-cell signal transduction have been reported by several
      laboratories, suggesting that tumors or host cells recruited to the tumor site
      actively down-regulate antitumor T-cell immune response. This permits tumor
      escape from immune-mediated killing. The possibility that defects in T-cell
      signal transduction can be reversed, which would potentially permit successful
      vaccination or adoptive immunotherapy, motivates renewed interest in the field.
      Summarizing the literature concerning tumor-induced T-cell dysfunction, we focus
      on the end stage of immune response to human cancer, that of defective cytotoxic
      T lymphocyte killing function. Based on the data from several laboratories, we
      hypothesize a biochemical mechanism that accounts for the unusual phenotype of
      antitumor T-cell accumulation in tumors, but with defective killing function.

PMID- 10972085
TI  - Human serum amyloid P component is a single uncomplexed pentamer in whole serum.
AB  - BACKGROUND: Serum amyloid P component (SAP) is a universal constituent of amyloid
      deposits and contributes to their pathogenesis. SAP also has important normal
      functions in the handling of chromatin in vivo and resistance to bacterial
      infection. The atomic resolution crystal structure of SAP is known, but its
      physiological oligomeric assembly remains controversial. In the absence of
      calcium, isolated human SAP forms stable decamers composed of two cyclic disk
      like pentamers interacting face to face. However, in the presence of its specific
      low molecular weight ligands and calcium, SAP forms stable pentamers. In the
      presence of calcium, but without any ligand, isolated human SAP aggressively
      autoaggregates and precipitates, imposing severe constraints on methods for
      molecular mass determination. MATERIALS AND METHODS: Gel filtration
      chromatography and density gradient ultracentrifugation were used to compare SAP
      with the closely related molecule, C-reactive protein (CRP; which is known to be
      a single pentamer) and the effect of human serum albumin on SAP autoaggregation
      was investigated. RESULTS: In most physiological buffers and with the necessary
      absence of calcium, SAP, whether isolated or from whole serum samples, eluted
      from gel filtration columns clearly ahead of CRP. This is consistent with the
      existence of a monodisperse population of SAP decamers, as previously reported.
      However, in Tris/phosphate buffer, SAP was pentameric, suggesting that
      decamerization involved ionic interactions. On density gradients formed in
      undiluted normal human serum, SAP sedimented as single pentamers not complexed
      with any macromolecular ligand, regardless of the presence or absence of calcium.
      The calcium-dependent autoaggregation of isolated SAP was completely inhibited by
      physiological concentrations of albumin and the SAP remained pentameric.
      CONCLUSIONS: Human SAP exists within serum as single uncomplexed pentamers in the
      presence or absence of calcium. This oligomeric assembly, thus, does not require
      a calcium-dependent small molecule interaction. The usual >2000-fold molar excess
      of albumin over SAP in plasma is apparently sufficient to keep SAP in its
      physiological conformation.

PMID- 10972086
TI  - Immunogenicity of an eight amino acid domain shared by Fas (CD95/Apo-I) and HIV-1
      gp120. I. Structural and antigenic analysis.
AB  - Previous studies have demonstrated that immunoglobulin G (IgG) antibodies to
      VEINCTR-N, a domain shared by Fas (CD95/Apo-I) and gp120, contribute to T-cell
      apoptosis during human immunodeficiency virus-type 1 (HIV-1) infection as a
      result of the agonist cross-linking of Fas. The present work was designed to
      determine whether these molecules are elicited primarily to HIV-1 or the cell
      receptor. MATERIALS AND METHODS: Sera from 439 HIV-1-infected patients were
      screened by ELISA for their reactivity to VEINCTR-N. Subjects with significant
      serum elevations of IgG anti-VEINCTR-N were further investigated. Immunologic
      parameters, including CD4+ and CD8+ lymphocyte count, extent of T-cell apoptosis,
      occurrence of both anti-Fas antibodies and circulating soluble Fas titers, and
      reactivity to the 8-mer peptides resembling the flank-regions of VEINCTR-N on
      both gp120 V3 loop and Fas were examined. In addition, the antigenicity of these
      domains was assessed by biochemical and computerized analyses. RESULTS: 21
      patients with significant levels of IgG to VEINCTR-N showed both an increased
      extent of peripheral T-cell apoptosis and binding to full-length Fas. A weak,
      though positive correlation of the anti-VEINCTR-N activity with its antecedent
      peptide on Fas was also found. Charge and structural analysis revealed that,
      although the extended 26-amino acid (a.a.) regions on both proteins were
      hydrophilic, the Fas peptide adjacent to VEINCTR-N expressed a short beta
      conformed a.a. sequence in contiguity with a portion of the shared epitope, also
      in beta-sheet conformation. Patterns of antigenicity confirmed an apparent
      immunodominance of the full VEINCTR-N, based on its homology with the consensus
      sequence of other members of the tumor necrosis factor (TNF) receptor family. The
      hypothesis that the high immunogenicity of this region of Fas, rather than gp120,
      can drive the production of anti-VEINCTR-N antibodies also was supported by the
      concurrent significant elevations of soluble Fas in almost all of the sera
      studied. CONCLUSIONS: Our results indicate that a high release of the soluble
      form of Fas by T cells during the chronic immune activation of HIV-1 infection
      primes a humoral response against this epitope of Fas as a result of its high
      antigenicity. This is similar to the antibodies to tumor necrosis factor alpha
      (TNFalpha) receptor (R) (TNFalpha-R) that occur in response to increased levels
      of the soluble receptor for TNF during autoimmunity.

PMID- 10972087
TI  - VEINCTR-N, an immunogenic epitope of Fas (CD95/Apo-I), and soluble Fas enhance T
      cell apoptosis in vitro. II. Functional analysis and possible implications in HIV
      1 disease.
AB  - BACKGROUND: Recent studies indicate that soluble Fas (sFas) may modulate T-cell
      apoptosis, since it inhibits Fas-ligand (Fas-L)-mediated cytotoxicity in vitro.
      Here, we explored whether the soluble receptor and its major immunogenic domain,
      namely VEINCTR-N, interfered with apoptosis of T cells from human
      immunodeficiency virus-type 1 (HIV-1)+ subjects showing serum elevations of both
      the soluble receptor and anti-Fas antibodies, and with that of several T-cell
      lines. MATERIALS AND METHODS: Both proliferation and apoptosis extent of T cells
      from 16 HIV-1+ patients showing serum anti-VEINCTR-N immunoglobulin G (IgG) and
      15 controls were tested after incubation with sFas and three 8-mer peptides of
      its first consensus sequence that included VEINCTR-N. Several cell lines were
      also investigated by flow cytometry for their expression of Ki-67, the APO2.7
      related mitochondrial protein, and the annexin-V. In addition, we evaluated the
      expression of Fas-L and caspases FLICE, CPP32 and ICE either by flow cytometry,
      immunoblotting, and/or reverse transcription polymerase chain reaction (RT-PCR).
      RESULTS: Cell proliferation in cultures from both patients and controls was
      affected significantly by sFas and VEINCTR-N. However, a prevalent increase of
      the subdiploid DNA-containing cell population occurred within these cultures.
      Similarly, Jurkat, CEM cells, and a mouse WR19L transformant overexpressing
      native human Fas underwent prompt apoptosis, which was detected as enlargement of
      APO2.7-reactive and annexin-V-positive populations. By exploring the Fas pathway
      in Jurkat cells, we found that both apoptosis inducers acted through Fas, since
      Fas-L, as well as CPP32 and FLICE were activated. By contrast, ICE was up
      regulated only in control cells treated with tumor necrosis factor alpha
      (TNFalpha). CONCLUSIONS: These data suggest that the soluble molecular forms of
      Fas prime cell death in Fas-positive cells. Therefore, the shedding of high
      amounts of sFas in HIV- 1 disease is possibly entrusted with amplification of the
      death execution program by cells functionally exhausted and committed to die. It
      is conceivable that the appearance of anti-Fas antibodies reflects an attempt by
      the immune system to neutralize these effective forms of the receptor and its
      structurally degraded domains, such as VEINCTR-N.

PMID- 10972088
TI  - Luteolin, an abundant dietary component is a potent anti-leishmanial agent that
      acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to
      apoptosis.
AB  - BACKGROUND: Plant-derived flavonoids, which occur abundantly in our daily dietary
      intake, possess antitumor, antibacterial, and free radical scavenging properties.
      They form active constituents of a number of herbal and traditional medicines.
      Several flavonoids have been shown to exert their action by interacting with DNA
      topoisomerases and promoting site-specific DNA cleavage. Therefore, flavonoids
      are potential candidates in drug design. We report here that, although the
      flavonoids luteolin and quercetin are potent antileishmanial agents, luteolin has
      great promise for acting as a lead compound in the chemotherapy of leishmaniasis,
      a major concern in developing countries. MATERIALS AND METHODS: Kinetoplast DNA
      (kDNA) minicircle cleavage in drug-treated parasites was measured by
      electrophoresis of the total cellular DNA, followed by Southern hybridization
      using 32P labeled kDNA as a probe. Cell cycle progression and apoptosis were
      measured by flow cytometry using propidium iodide and fluorescein isothiocyanate
      (FITC)-labeled Annexin V. RESULTS: Luteolin and quercetin inhibited the growth of
      Leishmania donovani promastigotes and amastigotes in vitro, inhibited DNA
      synthesis in promastigotes, and promoted topoisomerase-II-mediated linearization
      of kDNA minicircles. The IC50 values of luteolin and quercetin were 12.5 microM
      and 45.5 microM, respectively. These compounds arrest cell cycle progression in
      L. donovani promastigotes, leading to apoptosis. Luteolin has no effect on normal
      human T-cell blasts. Both luteolin and quercetin reduced splenic parasite burden
      in animal models. CONCLUSION: Luteolin and quercetin are effective
      antileishmanial agents. Quercetin has nonspecific effects on normal human T
      cells, but luteolin appears nontoxic. So, luteolin can be a strong candidate for
      antileishmanial drug design.

PMID- 10972089
TI  - Nitric oxide regulates MIP-1alpha expression in primary macrophages and T
      lymphocytes: implications for anti-HIV-1 response.
AB  - BACKGROUND: Chemokines and chemokine receptors have been shown to play a critical
      role in HIV infection. Chemokine receptors have been identified as coreceptors
      for viral entry into susceptible target cells, and several members of the beta
      chemokine subfamily of cytokines, MIP-1alpha, MIP-1beta, and RANTES, have been
      identified as the major human immunodeficiency virus (HIV)-suppressive factors
      produced by activated CD8+ T lymphocytes. In macrophages, HIV-1 infection itself
      was shown to upregulate the production of MIP-1alpha and MIP-1beta. In the
      present study, we address the mechanisms by which HIV-1 infection regulates beta
      chemokine responses in macrophages and lymphocytes. MATERIAL AND METHODS: To
      address whether nitric oxide (NO), generated as a consequence of HIV-1 infection,
      regulates beta chemokine responses in monocyte/macrophages and/or macrophage
      depleted peripheral blood mononuclear cells (PBMCs) these two cell populations
      were isolated from HIV seronegative donors, placed in culture, and infected with
      HIV-1 in either the presence or absence of exogenous activators (e.g.
      lipopolysaccharide, phytohemagglutinin), inhibitors of nitric oxide synthase
      (NOS), or chemical donors of NO. Cultures were analyzed for beta chemokine
      responses by ELISA and RNase protection. RESULTS: LPS-induced MIP-1alpha release
      is enhanced in HIV-1-infected, as compared to uninfected, monocyte/macrophage
      cultures, and this enhancing effect is partially blocked by the addition of
      inhibitors of NOS, and can be reproduced by chemical generators of NO even in the
      absence of HIV-1 infection. A similar strategy was used to demonstrate a role for
      NO in HIV-1-mediated induction of MIP-1alpha in unstimulated macrophage cultures.
      NOS inhibitors also decreased MIP-1alpha and MIP-1beta production by
      phytohemagglutinin-stimulated monocyte-depleted PBMC cultures. CONCLUSIONS: These
      results indicate that NO amplifies MIP-1alpha responses in activated macrophages
      and lymphocytes, and suggests that this pleiotropic molecule might function as an
      enhancing signal that regulates secretion of beta chemokines during HIV-1
      infection. These findings reveal a novel mechanism by which NO might regulate the
      anti-HIV activity of immune cells.

PMID- 10972090
TI  - Prurigo nodularis of Hyde: an update.
AB  - Prurigo nodularis of Hyde is an unusual disorder of unknown aetiology
      characterized by extremely pruritic nodules with well defined clinical and
      histopathological aspects. The literature on this disease is reviewed, focusing
      on the historical background, aetiology, pathogenesis, histopathology and
      ultrastructure, clinical aspects, differential diagnosis and therapeutic
      alternatives.

PMID- 10972091
TI  - One-year treatment of chronic urticaria with mizolastine: efficacy and safety.
      URTOL study group.
AB  - AIM: To assess the long-term safety and efficacy of the H1-receptor antagonist
      mizolastine in the symptomatic treatment of chronic urticaria (CU). BACKGROUND:
      Mizolastine is a novel second generation antihistamine with additional anti
      inflammatory properties which has been shown to be effective in this condition as
      well as in allergic rhinitis. As the drug is used for chronic treatment, a
      detailed study of its efficacy and safety over a prolonged period was warranted.
      METHODS: This open label multicentre trial recruited 211 patients suffering from
      CU (67% female; mean age 40+/-13 years), with > or = 1 episode/week if untreated.
      After a 7-day placebo run-in period, patients received mizolastine (10 or 15 mg)
      for 12 months. Efficacy was assessed by the patient using daily diary cards and
      overall condition evaluation at study visits. Clinicians also assessed the same
      parameters at each visit, and gave a global assessment at study termination.
      Safety was assessed by monitoring adverse events and laboratory parameters.
      Cardiac safety was monitored every 4 months using 12-lead ECGs, with particular
      attention to QT intervals. RESULTS: The trial was completed by 127 patients.
      Mizolastine reduced overall discomfort from the second week of therapy, and
      reduced itching and the number and size of wheals, as assessed by the patients.
      The clinician's assessment of the proportion of patients with > 10 wheals
      decreased from 42% to 28% after 2 months. Clinical assessment also indicated that
      itch intensity and angioedema were improved by mizolastine, and the improvement
      was sustained throughout the trial. The investigators estimated that 70% of
      patients benefited from therapy. There were no drug-related serious adverse
      events during the study. The cardiac repolarization assessed according to the QTc
      intervals was not modified during prolonged administration. CONCLUSION:
      Mizolastine improves CU symptoms, and these improvements are sustained over 12
      months with no loss of drug sensitivity. No specific side-effects are associated
      with its long-term use in the current study.

PMID- 10972092
TI  - Epidemiological study of classic Kaposi's sarcoma: a retrospective review of 125
      cases from Northern Israel.
AB  - BACKGROUND: The morphology of Kaposi's sarcoma is clinically and histologically
      the same in all clinical forms of the disease. However, there is a difference in
      the clinical and biological behaviour of the different forms of the disease. The
      behaviour also differs among individuals with the same form. The factors involved
      in the initiation and prognosis of the disease are still unknown. The classical
      form is more common in middle-aged Jews of East European or Mediterranean origin,
      people of Italian and southern Greek origin. Classic Kaposi's Sarcoma is seen
      relatively more frequently in Israel than in many other countries. OBJECTIVE: The
      aim of this study was to examine risk factors that influence the development and
      course of the disease. METHODS: This retrospective study includes 125 patients
      with Kaposi's sarcoma, all diagnosed and followed in the Department of
      Dermatology at Rambam Medical Center in Haifa. RESULTS: The group included 85
      (68%) men and 40 (32%) women. Fourteen subjects received corticosteroid therapy
      and three were kidney transplant recipients. Age at onset of the disease was 21
      87 years, with a mean age of 67. A total of 121 patients (96.8%) were Jews and
      four (3.2%) were non-Jews. A majority (61.6%) were of East European origin. The
      number of new cases each year was constant in relation to the general population,
      except for two peaks, one in 1970 and another in 1986-89. The lower limbs were
      involved in most patients. Extracutaneous involvement was present in 18.4%. Of
      all the subjects, 28 (22.4%) had diabetes mellitus and 21 (16.8%) had a second
      primary malignancy. The malignancies were of lymphoreticular origin in 10
      patients, four in the urinary bladder, three had carcinoma of the large bowel and
      one of the pancreas. CONCLUSION: Our study shows similar clinical findings to
      those described in other series. The relatively high frequency of carcinomas of
      the colon and urinary bladder was not reported elsewhere. We observed a
      consistent rate of new cases each year with two peaks in 1970 and 1986-1989, the
      cause of which deserves explanation. Of interest is the relative rise in the
      number of females with Kaposi's sarcoma. A relative high risk for developing
      Kaposi's sarcoma has been found among Jews of Ashkenazi origin compared to those
      of other ethnic groups. Israeli-born subjects presented a relatively more
      aggressive course of disease than others.

PMID- 10972093
TI  - Effects of lithium carbonate (Li2CO3) on in-vitro-cultured normal human skin
      explants.
AB  - The early morphological changes induced by lithium carbonate, a well-known
      psoriasis-provoking drug, were studied on cultured skin. Normal human skin from
      patients undergoing mastectomy was cultured in the presence of 3 mM, 6 mM and 10
      mM of Li2CO3 for 4 days. The morphological changes were then evaluated by three
      observers in a blind manner and their reports were matched and collated. The
      cultured skin in the presence of Li2CO3 showed cell crowding of keratinocytes in
      the lower part of the epidermis, indicating epidermal hyperplasia. Another
      striking finding was intercellular oedema and vacuolar alteration with formation
      of small cavities in the upper dermis. There was no evidence of parakeratosis or
      any other histological characteristic of psoriasis, except hyperproliferation of
      the epidermis. Based on our knowledge of mechanisms of lithium action, we
      proposed two competitive explanations for its action on the epidermis: i) that
      lithium acts directly on dividing cells of the epidermis; and ii) that it acts
      indirectly by altering epidermal barrier function. Although we lack definite
      proof, we suggest that the observed morphological changes, in particular the non
      specific stimulus to epidermal proliferation, are the primary events which
      initiate the process that will ultimately lead to the development of psoriasis in
      a predisposed patient.

PMID- 10972094
TI  - Purpuric contact dermatitis in patients with allergic reaction to textile dyes
      and resins.
AB  - BACKGROUND: Purpuric lesions have been described as an uncommon manifestation of
      allergic contact dermatitis in individual case reports. OBJECTIVE: We describe a
      series of patients who developed purpuric allergic contact dermatitis to textile
      dyes and resins in their personal clothing. Our purpose was to study the patients
      clinically and histopathologically and to define the most frequent allergens,
      which cause purpuric allergic contact dermatitis. METHODS: One hundred and three
      patients were clinically evaluated and tested with the Textile Color & Finish
      Series (TCFS) (Chemotechnique Diagnostics) and Standard Series (TRUE Tests)
      because of suspected allergic contact dermatitis (ACD) to clothing. The patients
      with clinical features of purpura as presenting sign of ACD were studied.
      Biopsies from the purpuric lesions were performed in three patients. RESULTS:
      Thirty of the 103 patients (29.1%) had positive reaction to an allergen from the
      TCFS. Clinically purpuric ACD was observed in 8.7% of all the cases studied (n =
      9 of 103). Nine of the 30 patch-positive patients to the TCFS (30%) demonstrated
      purpuric macules, papules and patches. Patch testing of the nine patients with
      purpuric contact dermatitis, with the TCFS, resulted in 26 positive patch test
      results. The major causative allergens were the following: Disperse Blue 106 and
      Disperse Blue 124 in 26.9% each, Disperse Blue 85 in 11.5%, and ethyleneurea
      melamine formaldehyde in 7.7%. Positive patch tests were observed to dimethylol
      dihydroxyethyleneurea, dimethylol propyleneurea, tetramethylol acetylenediurea,
      urea formaldehyde, melamine formaldehyde, Disperse Red 17, and Basic Red 46 3.8%
      in each. Purpuric patch test reaction was observed in five cases. The patch test
      results had present relevance in all the cases. Lesional biopsies demonstrated
      acanthosis, spongiosis and parakeratosis. The blood vessels were dilated, without
      signs of vasculitis. The inflammatory infiltrate was composed of lymphocytes and
      erythrocytes. The extravasated erythrocytes had a perivascular and interstitial
      distribution in the superficial and deep plexus and were observed at the dermo
      epidermal junction as well as in the epidermis. CONCLUSION: Purpuric contact
      dermatitis is not an uncommon clinical form of ACD to textile dyes and resins.
      New allergens, which can evoke the development of purpuric allergic contact
      dermatitis and have not been described in the literature until now include:
      ethyleneurea melamineformaldehyde, dimethylol dihydroxyethyleneurea,
      tetramethylol acetylenediurea, urea formaldehyde, melamine formaldehyde and
      Disperse Red 17.

PMID- 10972096
TI  - Cutaneous primary paracoccidioidomycosis.
AB  - Paracoccidioidomycosis is a common fungal infection in Latin America. Few cases
      have been described in non-endemic countries and their diagnosis without the
      correct suspicion, bearing in mind that the latency period might be up to 60
      years, may not be easy. We report the case of a 59-year-old man who worked as a
      taxi driver for 25 years in Venezuela. Cutaneous paracoccidioidomycosis was
      diagnosed one year after he returned to Spain. No internal signs or symptoms of
      the disease were found and cell-mediated immunity showed no depression. Our case
      suggested us to consider direct cutaneous infection, although respiratory tract
      is believed to be the most frequent portal of entry for this infection.

PMID- 10972095
TI  - Atopic diseases among adults in the two geographically related arctic areas
      Nikel, Russia and Sor-Varanger, Norway: possible effects of indoor and outdoor
      air pollution.
AB  - BACKGROUND: Previous studies have shown lower prevalence of atopic diseases among
      adults and school-children in Eastern Europe. OBJECTIVES: To compare the
      prevalence of atopic diseases among adults in two geographically related arctic
      areas, Nikel, Russia and Sor-Varanger, Norway. Nikel is a heavily polluted town
      on the Kola Peninsula. METHODS: The prevalence of eczema, asthma and allergic
      rhinoconjunctivitis (AR) was assessed using two identical questionnaire studies.
      The study in Sor-Varanger was conducted in the autumn of 1991 and comprised 1102
      adults. In the spring of 1994, 3368 adults in Nikel completed the 4-page
      questionnaire. Results The lifetime prevalence of atopic diseases was
      significantly higher in Sor-Varanger than in Nikel (25.2% vs. 11.2%; P < 0.001),
      most pronounced for eczema (15.9% vs. 5.9%; P < 0.001) and AR (10.3% vs. 5.6%; P
      < 0.001). There was no significant difference in the prevalence of asthma between
      the two areas (5.6% vs. 4.9%; RR 1.1). Indoor dampness, carpeted floors and
      outdoor pollution were found to be significantly higher in Nikel than in Sor
      Varanger (P < 0.0001). Smoking habits were different in the two areas.
      CONCLUSION: Atopic diseases in Sor-Varanger were more than twice that found in
      Nikel. Western lifestyle and new building techniques resulting in poorly
      ventilated homes may be the main reasons for these differences. Other factors,
      such as differences in seeking medical help for physical complaints and in the
      social and political environment, are also suggested.

PMID- 10972097
TI  - Familial mastocytosis associated with neurosensory deafness.
AB  - Mastocytosis is a disease characterized by excessive accumulation of mast cells
      in different tissues and symptoms caused by the release of mast cell mediators.
      The skin is frequently directly involved in mastocytosis. The disease is rarely
      seen in other members of the subjects' family; only 49 cases of familial
      mastocytosis have been reported. Familial mastocytosis associated with hearing
      loss may represent a newly described inherited entity. We describe a brother and
      sister exhibiting skin mastocytosis and neurosensory deafness, associated with a
      history of hearing loss in their father's family. The appearance of the mast cell
      disease in two siblings, who presented with similar clinical features represents
      a familial form of mastocytosis; the association with an inherited form of
      deafness may constitute a new syndrome. Our patients show several features
      similar to some previously reported cases but different insofar that additional
      congenital defects and mental retardation are absent.

PMID- 10972099
TI  - Angiokeratoma corporis diffusum (Anderson-Fabry's disease): a case report.
AB  - We report on a 14-year-old boy who presented with a 4-year history of acral pains
      and febrile episodes. On physical examination, numerous small reddish papules
      were present on his abdomen, located predominantly on the periumbelical region.
      Renal function was within normal limits. Ophthalmological examination revealed
      whorled opacities of the cornea (cornea verticillata) and dilated tortuous
      conjunctival vessels. Histopathological examination of one of the cutaneous
      papules showed several dilated blood vessels in the superficial dermis surrounded
      by collarettes of thickened rete ridges, consistent with a diagnosis of
      angiokeratoma. The electron-microscopic study of a skin specimen demonstrated the
      presence of dilated lysosomes with deposition of electron-dense bodies, some of
      which with laminated structure, in endothelial cells and fibroblasts. These
      findings were regarded as indicative of Fabry's disease. Subsequent biochemical
      analysis confirmed the presence of a alpha-galactosidase A deficiency in
      leukocytes. In conclusion, we described the clinical, histopathological and
      submicroscopic findings of a case of Fabry's disease, in which the combination of
      electron microscopic and biochemical approaches allowed the correct diagnosis.

PMID- 10972098
TI  - Oral carcinoma in a young man: a case of dyskeratosis congenita.
AB  - We report a 28-year-old male with a voluminous growth of the tongue, present for
      6 months. The histological examination revealed a squamous cell carcinoma. The
      patient was also affected by oral leukoplakia, nail dystrophy, reticulated
      poikiloderma of the neck and hyperkeratosis of palms and soles. On the basis of
      clinical features and histological findings, as well as findings from the family,
      the diagnosis of dyskeratosis congenita (DKC) was made.

PMID- 10972100
TI  - Calcipotriol treatment of confluent and reticulated papillomatosis (Gougerot
      Carteaud syndrome).
AB  - Gougerot-Carteaud syndrome or confluent and reticulated papillomatosis (CRP), was
      first described by Gougerot and Carteaud as dermatosis. It is generally
      considered a rare condition. The eruption consists confluent, flat, brown papules
      localized primarily to the intermammary and interscapular regions with subsequent
      spread to the breast and abdomen; at the periphery, the papules spread out
      forming a pigmented reticulated pattern. At present, the aetiology of CRP remains
      unknown. The two prominent theories are an abnormal host response to fungi and a
      keratinization defect. Other hypothesis include photosensitivity, genetic factor,
      amyloidosis cutis and endocrinopathy.

PMID- 10972101
TI  - Lichen amyloidosis, ankylosing spondylitis and autoimmune thyroiditis:
      coincidence or association?
AB  - Primary localized cutaneous amyloidosis (PLCA) is characterized by the deposition
      of amyloid in a previously apparently normal skin with the absence of other
      systemic or cutaneous disorder. Although ankylosing spondylitis may be associated
      with secondary systemic amyloidosis, no reports have been found showing the
      association of this disease with PLCA. In addition, the association of PLCA with
      autoimmune thyroiditis has not been previously reported. We report a concomitant
      occurrence of lichen amyloidosis, ankylosing spondylitis and autoimmune
      thyroiditis in a caucasian woman.

PMID- 10972103
TI  - Toxic epidermal necrolyis (TEN) in a patient with non-Hodgkin lymphoma:
      successful treatment with dexamethasone at high dosage.

PMID- 10972102
TI  - Bullous acral erythema and concomitant pigmentation on the face and occluded
      skin.

PMID- 10972104
TI  - Botulinum A toxin for wrinkles: release from tension headache.

PMID- 10972105
TI  - Thick skin syndrome in diabetes mellitus.

PMID- 10972106
TI  - A case of multiple facial painless leiomyomata.

PMID- 10972107
TI  - Select committee's concerns about farm support measures.

PMID- 10972108
TI  - Plan for action on veterinary medicines.

PMID- 10972109
TI  - Eradication of sarcoptic mange from a Belgian pig breeding farm with a
      combination of injectable and in-feed ivermectin.
AB  - Sarcoptes scabiei var suis was eradicated from a Belgian pig farm by using a
      combination of injections of ivermectin and ivermectin in the feed. The detection
      of mites in ear scrapings, and calculations of an average dermatitis score and a
      scratching index were used to evaluate the mange status of the pigs before and
      after the treatment. Before the treatment 28 per cent of ear scrapings of
      finishers were positive for the presence of mites, their average dermatitis score
      (ADS) was 0.92 and their scratching index was 2.0. There was a significant
      decrease in all three measurements during the year after the treatment, and one
      year after treatment, no mites were found in the ear scrapings; the ADS of the
      finishers was 0.31 and their scratching index was 0.16. Adult animals were
      negative for the presence of mites at all times, the ADS was below the cut-off
      level before and after treatment, and the scratching index decreased after
      treatment There was an economic improvement among the breeding sows and the
      fattening pigs. The feed consumption of the sows decreased by 5 per cent;
      rebreeding decreased by 4.55 per cent; average litter size increased by 0.33 live
      piglets born per litter and the farrowing index increased by 0.075 litters per
      sow per year. As a result, the production index increased by 1.34 more piglets
      weaned per sow per year. There was an immediate improvement in feed conversion
      during the five months after the treatment. The costs of the treatment were
      recovered within 3.7 months.

PMID- 10972110
TI  - Transportation of ostriches--a review.

PMID- 10972111
TI  - Epidemiological characteristics and financial costs of the 1997 foot-and-mouth
      disease epidemic in Taiwan.
AB  - Between March and July 1997, a devastating outbreak of foot-and-mouth disease
      (FMD), serotype O, occurred in pigs in Taiwan. A total of 6,147 pig farms with
      more than 4 million pigs were infected, and 37.7 per cent of the pigs in Taiwan
      either died (0.18 million pigs) or were killed (3.85 million pigs). The epidemic
      reached its peak during the fifth week after it was first recognised. During the
      eighth and ninth weeks, a two-dose blanket vaccination programme was instituted
      which led to a large reduction in new outbreaks. Except for two cities, the whole
      of Taiwan was declared an FMD-infected zone. During the four months in which new
      farm outbreaks occurred, 21.7 per cent of the pigs on infected farms showed
      clinical signs, and there was an overall mortality of 3.95 per cent. During the
      early stages of the epidemic, the incubation period was as short as 24 hours and
      the case fatality rates for suckling piglets reached 100 per cent. The financial
      cost of the epidemic was estimated at US$ 378.6 million, including indemnities,
      vaccines, carcase disposal plus environmental protection, miscellaneous expenses,
      and loss of market value. Owing to the ban on exports of pork to Japan, it is
      estimated that the total economic cost to Taiwan's pig industry will be about US$
      1.6 billion.

PMID- 10972112
TI  - Competitive ELISA for bovine brucellosis suitable for testing poor quality
      samples.

PMID- 10972113
TI  - Reaction of farmed mink (Mustela vision) to argon-induced hypoxia.

PMID- 10972114
TI  - Metastatic mammary adenocarcinomas in two beluga whales (Delphinapterus leucas)
      from the St Lawrence Estuary, Canada.

PMID- 10972115
TI  - Bovine tuberculosis in housed calves.

PMID- 10972116
TI  - Use of Rimadyl in cats.

PMID- 10972117
TI  - Lungworm infection in housed calves.

PMID- 10972118
TI  - Reindeer concerns.

PMID- 10972119
TI  - Chemoreception, symmetry and mate choice in lizards.
AB  - Research on fluctuating asymmetry (FA)-mediated sexual selection has focused
      almost exclusively on visual signals and ignored chemical communication despite
      the fact that many species rely on chemical signals for attracting mates. Female
      mate choice based on visual traits appears to be rare in lizards. However, the
      femoral glands of male lizards produce pheromones which might transmit chemical
      information about an individual's developmental stability. Therefore, we
      hypothesized that mate choice may be based on chemical cues. We analysed the
      effect of the developmental stability levels of males on the attractiveness of
      males' scents to females in a laboratory experiment with the lizard Lacerta
      monticola. When we offered two males of similar body size, females preferentially
      associated with the scents of males with low FA in their femoral pores and also
      with the scents of males with a higher number of femoral pores. This suggested
      that the females were able to discriminate the FA of the males by chemical
      signals alone and that the females preferred to be in areas marked by males of
      high quality, thus increasing their opportunities of mating with males of high
      quality. We suggest that the quality and/or amount of male pheromones could
      communicate the heritable genetic quality of a male to the female and thereby
      serve as the basis for adaptive female choice in lizards.

PMID- 10972120
TI  - Sexual cooperation and conflict in butterflies: a male-transferred anti
      aphrodisiac reduces harassment of recently mated females.
AB  - Sexual selection theory predicts that the different selection pressures on males
      and females result in sexual conflict. However, in some instances males and
      females share a common interest which could lead to sexual cooperation. In the
      pierid butterfly Pieris napi the male and the recently mated female share a
      common interest in reducing female harassment by other males soon after mating.
      Here we show that P. napi males transfer an anti-aphrodisiac to the female at
      mating, methyl-salicylate (MeS), which is a volatile substance which mated
      females emit when courted and which makes males quickly abandon them. A 13C
      labelling experiment demonstrated that only males synthesize MeS. The effect of
      this antiaphrodisiac is so strong that most males will refrain from mating with
      virgin females to whom MeS has been artificially applied. In P. napi, males also
      transfer nutrients to females at mating. This increases female fecundity and
      longevity and so females benefit from remating. Hence, sexual cooperation
      gradually turns to conflict. Future research is required to reveal which sex
      controls the gradual decrease in the MeS titre which is necessary for allowing
      mated females to regain attractiveness and remate.

PMID- 10972121
TI  - Wolbachia infection frequencies in insects: evidence of a global equilibrium?
AB  - Wolbachia are a group of cytoplasmically inherited bacteria that cause
      reproduction alterations in arthropods, including parthenogenesis, reproductive
      incompatibility, feminization of genetic males and male killing. Previous general
      surveys of insects in Panama and Britain found Wolbachia to be common, occurring
      in 16-22% of species. Here, using similar polymerase chain reaction methods, we
      report that 19.3% of a sample of temperate North American insects are infected
      with Wolbachia, a frequency strikingly similar to frequencies found in two other
      studies in widely separated locales. The results may indicate a widespread
      equilibrium of Wolbachia infection frequencies in insects whose maintenance
      remains to be explained. Alternatively, Wolbachia may be increasing in global
      insect communities. Within each of the three geographic regions surveyed,
      Hymenoptera are more frequently infected with A group Wolbachia and Lepidoptera
      more frequently infected with B group Wolbachia.

PMID- 10972122
TI  - On the advantages of information sharing.
AB  - During the evolution of life, there have been several transitions in which
      individuals began to cooperate, forming higher levels of organization, and
      sometimes losing their independent reproductive identity For example,
      multicellularity and insect societies evolved independently multiple times.
      Several factors that confer evolutionary advantages on higher levels of
      organization have been proposed. In this paper we highlight one additional
      factor: the sharing of information between individuals. Information sharing is
      not subject to the intrinsic conservation laws that characterize the sharing of
      physical resources. A simple model will illustrate how information sharing can
      result in aggregates in which the individuals both receive more information about
      their environment and pay less for it. This may have played a role in the
      evolution of higher levels of organization.

PMID- 10972123
TI  - The possible role of reaction-diffusion in leaf shape.
AB  - We consider mechanisms that may determine certain simple leaf shapes. Compared
      with other aspects of plant morphogenesis, such as phyllotaxis or spiral leaf
      arrangement, rather little is known about leaf-shape-determining mechanisms. We
      develop mathematical models for the gross pattern of leaf shape based on reaction
      diffusion systems. These models are consistent with what is known about factors
      that might determine leaf shape. They show that diverse leaf shapes may be
      obtained from a single reaction diffusion system. This has implications in terms
      of both convergent and divergent evolution. The models make predictions that can
      be tested experimentally. We predict the form of pre-patterns of growth promoters
      in leaf primordia of different sizes when the morphogens either diffuse into the
      primordia or are produced locally. We also predict the effects on leaf shape of
      removing parts of primordia at different times. The models can also predict the
      effects on leaf shape of the topical application of activators and inhibitors to
      leaf primordia.

PMID- 10972124
TI  - Correlations in fossil extinction and origination rates through geological time.
AB  - Recent analyses have suggested that extinction and origination rates exhibit long
      range correlations, implying that the fossil record may be controlled by self
      organized criticality or other scale-free internal dynamics of the biosphere.
      Here we directly test for correlations in the fossil record by calculating the
      autocorrelation of extinction [corrected] and origination rates through time. Our
      results show that extinction rates are uncorrelated beyond the average duration
      of a stratigraphic interval. Thus, they lack the long-range correlations
      predicted by the self-organized criticality hypothesis. In contrast, origination
      rates show strong autocorrelations due to long-term trends. After detrending,
      origination rates generally show weak positive correlations at lags of 5-10
      million years (Myr) and weak negative correlations at lags of 10-30 Myr,
      consistent with aperiodic oscillations around their long-term trends. We
      hypothesize that origination rates are more correlated than extinction rates
      because originations of new taxa create new ecological niches and new
      evolutionary pathways for reaching them, thus creating conditions that favour
      further diversification.

PMID- 10972125
TI  - Extinction dynamics and the regional persistence of a tree frog metapopulation.
AB  - The concept of a metapopulation acknowledges local extinctions as a natural part
      of the dynamics of a patchily distributed population. However, if extinctions are
      not balanced by recolonizations or if there is a high degree of spatial synchrony
      of local extinctions, this poses a threat to and will reduce the metapopulation
      persistence time. Here we show that, in a metapopulation network of 378 pond
      patches used by the tree frog (Hyla arborea), even though extinctions are
      frequent (mean extinction probability p(e) = 0.24) they pose no threat to the
      metapopulation as they are balanced by recolonizations (p(c) = 0.33). In any one
      year there was a pattern of large populations tending to persist while small
      populations became extinct. The total number of individuals belonging to
      populations that went extinct was small (< 5%) compared with those populations
      that persisted. A spatial autocorrelation analysis indicated no clustering of
      local extinctions. The tree frog metapopulation studied consisted of a set of
      larger, persistent populations mixed with smaller populations characterized by
      high turnover dynamics.

PMID- 10972126
TI  - Adaptation to marginal habitats: contrasting influence of the dispersal rate on
      the fate of alleles with small and large effects.
AB  - The focus of this paper is the relationship between the dispersal rate and the
      conditions for invasion of a rare allele that improves performance in a marginal
      sink habitat at the expense of reducing fitness in the main source habitat.
      Classic multiple-niche population-genetic models predict that the conditions for
      the invasion of such an allele always become more favourable as the dispersal
      rate decreases. Precisely the opposite prediction was reached in demographic
      fitness-sensitivity studies. This study reconciles those contradictory
      predictions and identifies the assumptions responsible for the discrepancy. I
      show that whether a lower dispersal rate makes the conditions for the invasion of
      the allele more or less stringent depends on the magnitude of the effects of the
      allele. If the effect is large relative to the degree of maladaptedness of the
      original genotype to the marginal habitat, the conditions become less stringent
      with decreasing dispersal rate. The opposite is the case for mutations with very
      small effects. For a broad range of mutations with intermediate effects the
      conditions are most stringent under an intermediate dispersal rate.

PMID- 10972127
TI  - Heterosis increases the effective migration rate.
AB  - Individuals coming from the same subpopulation are more likely to share
      deleterious mutations at any given locus than hybrids formed between parents from
      different populations. Offspring of migrants therefore may experience heterosis
      and have higher fitness than resident individuals. This will, in turn, result in
      the immigrant alleles being present in higher frequencies than predicted from
      neutral expectations and thus a higher effective migration rate. In this paper we
      derive a formula to calculate the effective migration rate in the presence of
      heterosis. It is shown that the effect of heterosis on the migration rate can be
      substantial when fitness reduction within local populations is severe. The effect
      will be more pronounced in species with relatively short map lengths. Furthermore
      the heterosis effect will be highly variable throughout the genome, with the
      largest effect seen near selected genes and in regions of high gene density.

PMID- 10972128
TI  - Population consequences of reproductive decisions.
AB  - Behaviour can be a key component of animal population ecology yet the population
      consequences of behavioural decisions are poorly understood. We conducted a
      behavioural and demographic study of the bitterling Rhodeus sericeus, a
      freshwater fish that spawns in live unionid mussels. We used a population model
      incorporating game theory decisions and measurements of demographic parameters in
      order to provide predictions of population size among 13 populations of this
      fish. Our model predicted that the observed behavioural spawning decisions, while
      maximizing individual fitness, cause a significant 6% reduction in population
      size compared with randomly distributed spawnings. We discuss our findings in the
      context of the population consequences of adaptive behaviour.

PMID- 10972129
TI  - Low mass-specific brain Na+/K+-ATPase activity in elasmobranch compared to
      teleost fishes: implications for the large brain size of elasmobranchs.
AB  - Elasmobranch fishes have long been noted for having unusually large brains for
      ectotherms, and therefore may be exceptions to the rule that vertebrates in
      general devote less than 8% of their resting metabolic rate to the central
      nervous system. The brain mass of sharks, skates and rays is often several times
      larger than that of teleost fishes of the same size. Still, the underlying
      reasons for this have remained unclear. Ion pumping by the Na+/K+-ATPase is the
      single most energy consuming process in the brain. In this study, Na+/K+-ATPase
      activity was measured in the brain of four species of elasmobranchs and 11
      species of teleosts. While the average brain mass of the elasmobranchs examined
      was approximately three times that of the teleosts, the mean specific Na+/K+
      ATPase activity was only about one-third of that of the teleosts. Thus, the total
      brain Na+/K+-ATPase activity was similar in elasmobranchs and teleosts. This
      suggests that the large brain size of elasmobranchs is at least partly related to
      a low mass-specific rate of brain energy use.

PMID- 10972130
TI  - Apparent position governs contour-element binding by the visual system.
AB  - An assumption inherent in many models of visual space is that the spatial
      coordinates of retinal cells implicitly give rise to the perceptual code for
      position. The results of the experiments reported here, in which it is shown that
      retinally non-veridical locations of contour elements are used by the visual
      system for contour-element binding, lend support to a different view. The visual
      system does not implicitly code position with reference to the labelled locations
      of retinal cells, but dynamically extracts spatial position from the aggregate
      result of local computations. These computations may include local spatial
      relationships between retinal cells, but are not confined to them; other
      computations, including position derived from local velocity cues, are combined
      to code the position of objects in the visual world.

PMID- 10972131
TI  - HIV-1 dynamics revisited: biphasic decay by cytotoxic T lymphocyte killing?
AB  - The biphasic decay of blood viraemia in patients being treated for human
      immunodeficiency virus type 1 (HIV-1) infection has been explained as the decay
      of two distinct populations of cells: the rapid death of productively infected
      cells followed by the much slower elimination of a second population the identity
      of which remains unknown. Here we advance an alternative explanation based on the
      immune response against a single population of infected cells. We show that the
      biphasic decay can be explained simply, without invoking multiple compartments:
      viral load falls quickly while cytotoxic T lymphocytes (CTL) are still abundant,
      and more slowly as CTL disappear. We propose a method to test this idea, and
      develop a framework that is readily applicable to treatment of other infections.

PMID- 10972132
TI  - The mimetic transition: a simulation study of the evolution of learning by
      imitation.
AB  - Culturally transmitted ideas or memes must have had a large effect on the
      survival and fecundity of early humans. Those with better techniques of obtaining
      food and making tools, clothing and shelters would have had a substantial
      advantage. It has been proposed that memes can explain why our species has an
      unusually large brain and high cognitive ability: the brain evolved because of
      selection for the ability to imitate. This article presents an evolutionary model
      of a population in which culturally transmitted memes can have both positive and
      negative effects on the fitness of individuals. It is found that genes for
      increased imitative ability are selectively favoured. The model predicts that
      imitative ability increases slowly until a mimetic transition occurs where memes
      become able to spread like an epidemic. At this point there is a dramatic
      increase in the imitative ability, the number of memes known per individual and
      the mean fitness of the population. Selection for increased imitative ability is
      able to overcome substantial selection against increased brain size in some
      cases.

PMID- 10972133
TI  - What is the function of receptor and membrane endocytosis at the postsynaptic
      neuron?
AB  - This paper explores the implications of certain new developments in cell biology
      upon neuroscience. Until recently it was thought that neurotransmitters and
      neuromodulators had only one function, which was to stimulate their specific
      receptors at the cell surface. From here on, all activity was supposed to be
      effected by postsynaptic cascades. The discovery that membrane components,
      particularly G-protein-linked receptors, are not static but are subject to a
      massive and complex process of continual endocytosis, processing in the endosome
      system and recycling back to the external membrane, raises the question of its
      functional significance. In addition, it has been found that many neuromodulators
      such as polypeptides have their main locus of action inside the postsynaptic
      neuron. This review covers the role of the endocytic mechanism on receptor
      desensitization and resensitization, synaptic reorganization and plasticity
      synaptic scaling and the possible repair of oxidative damage. The possible
      involvement of this system in Alzheimer's disease is discussed.

PMID- 10972134
TI  - Cue combination in the motion correspondence problem.
AB  - Image motion is a primary source of visual information about the world. However,
      before this information can be used the visual system must determine the spatio
      temporal displacements of the features in the dynamic retinal image, which
      originate from objects moving in space. This is known as the motion
      correspondence problem. We investigated whether cross-cue matching constraints
      contribute to the solution of this problem, which would be consistent with
      physiological reports that many directionally selective cells in the visual
      cortex also respond to additional visual cues. We measured the maximum
      displacement limit (Dmax) for two-frame apparent motion sequences. Dmax increases
      as the number of elements in such sequences decreases. However, in our displays
      the total number of elements was kept constant while the number of a subset of
      elements, defined by a difference in contrast polarity, binocular disparity or
      colour, was varied. Dmax increased as the number of elements distinguished by a
      particular cue was decreased. Dmax was affected by contrast polarity for all
      observers, but only some observers were influenced by binocular disparity and
      others by colour information. These results demonstrate that the human visual
      system exploits local, cross-cue matching constraints in the solution of the
      motion correspondence problem.

PMID- 10972135
TI  - Haptoglobin glycoforms in a case of carbohydrate-deficient glycoprotein syndrome.
AB  - Alterations in haptoglobin (Hp) glycosylation were examined in the plasma of the
      first patient with carbohydrate-deficient glycoprotein syndrome (CDGS) who was
      described in Poland. Hp concentration in the CDGS patient plasma was low (240
      mg/l) and the Hp phenotype was shown to be 2-2. Three glycoforms of the Hp beta
      subunit were observed in SDS-PAGE in CDGS. The densitometric analysis and
      molecular weight determinations suggested that 50% of glycoforms were fully
      glycosylated; 30% contained three out of four and 20% only two out of four glycan
      units compared to those that are present in Hp derived from healthy people.
      Results with lectins (concanavalin A and Sambucus nigra, Maackia amurensis and
      Alleuria aurantia agglutinins) indicate that all three glycoforms of beta subunit
      of CDGS-Hp contained biantennary complex glycans terminated with alpha2,6 bound
      sialic acid, but without fucose or alpha2,3 linked sialic acid. Hp glycosylation
      abnormalities described in this work suggest that this case was a type I
      carbohydrate-deficient glycoprotein syndrome.

PMID- 10972136
TI  - Application of square-wave adsorptive stripping voltammetry to the study of
      cysteine and its interaction with some monosaccharides.
AB  - The square-wave adsorptive stripping voltammetric behaviour of cysteine at the
      physiological pH (7.40) has been optimised with respect to accumulation time,
      accumulation potential, scan rate and drop size. This study describes the
      application of voltammetry to studies on the interaction of cysteine with
      monosaccharides.

PMID- 10972137
TI  - Total synthesis of a cholinergic neuron-specific ganglioside GT1a alpha: a high
      affinity ligand for myelin-associated glycoprotein (MAG).
AB  - An efficient total synthesis of a cholinergic neuron-specific ganglioside GT1a
      alpha (IV3NeuAcIII6NeuAcII3NeuAc-GgOse4Cer) is described. The suitably protected
      sialyl-alpha(2-->6)-gangliotriose (III6NeuAc-GgOse3) derivative was glycosylated
      with the phenyl 2-thioglycoside of sialic acid in the presence of N
      iodosuccinimide (NIS) and trimethylsilyl trifluoromethane-sulfonate (TMSOTf) in
      acetonitrile medium, giving the disialogangliotriose (III6NeuAcII3NeuAc-GgOse3)
      derivative which contains both sialyl-alpha(2-->6)-GalNAc and sialyl-alpha(2-->3)
      Gal structures (Route I). This pentasaccharide was efficiently synthesized also
      by the coupling of (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D
      glycero-alpha-D-galacto -2-nonulopyranosylonate)-(2-->6)-2-deoxy-3,4-O
      isopropylidene-2-ph thalimido-D-galactopyranosyl trichloroacetimidate with 2
      (trimethylsilyl)ethyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D
      glycero-alpha-D-galacto -2-nonulopyranosylonate)-(2-->3)-(2,6-di-O-benzyl-beta-D
      galactopy ranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, followed by
      conversion of the phthalimido group to the acetamido group (Route II). O
      Deisopropylidenation and further glycosylation with methyl (methyl 5-acetamido
      4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-gala ct-2
      nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-b eta-D
      galactopyranoside, promoted by dimethyl(methylthio)sulfonium triflate (DMTST),
      gave the desired trisialogangliotetraose (IV3NeuAcIII6NeuAcII3NeuAc-GgOse4)
      derivative, which was converted stepwise into the title ganglioside GT1a alpha by
      the introduction of the ceramide part and then complete deprotection. The
      ganglioside obtained was shown to be identical with the native GT1a alpha on TLC
      immunostaining.

PMID- 10972138
TI  - Synthesis of the acceptor analog alphaFuc(1-->2)alphaGal-O(CH2)7 CH3: a probe for
      the kinetic mechanism of recombinant human blood group B glycosyltransferase.
AB  - We report the chemical synthesis of alphaFuc(1-->2)alphaGal-O(CH2)7CH3 (1) an
      analog of the natural blood group (O)H disaccharide alphaFuc(1-->2)betaGal-OR.
      Compound 1 was a good substrate for recombinant blood group B glycosyltransferase
      (GTB) and was used as a precursor for the enzymatic synthesis of the blood group
      B analog (alphaGal(-->3)alphaFuc(1-->2)]alphaGal-O(CH2)7CH3+ ++ (2). To probe the
      mechanism of the GTB reaction, kinetic evaluations were carried out employing
      compound 1 or the natural acceptor disaccharide alphaFuc(1-->2)betaGal-O(CH2)7CH3
      (3) with UDP-Gal and UDP-GalNAc donors. Comparisons of the kinetic constants for
      alternative donor and acceptor pairs suggest that the GTB mechanism is Theorell
      Chance where donor binding precedes acceptor binding. GTB operates with retention
      of configuration at the anomeric center of the donor. Retaining reactions are
      thought to occur via a double-displacement mechanism with formation of a glycosyl
      enzyme intermediate consistent with the proposed Theorell-Chance mechanism.

PMID- 10972139
TI  - A solid-phase glycosyltransferase assay for high-throughput screening in drug
      discovery research.
AB  - Glycosyltransferases mediate changes in glycosylation patterns which, in turn,
      may affect the function of glycoproteins and/or glycolipids and, further
      downstream, processes of development, differentiation, transformation and cell
      cell recognition. Such enzymes, therefore, represent valid targets for drug
      discovery. We have developed a solid-phase glycosyltransferase assay for use in a
      robotic high-throughput format. Carbohydrate acceptors coupled covalently to
      polyacrylamide are coated onto 96-well plastic plates. The glycosyltransferase
      reaction is performed with recombinant enzymes and radiolabeled sugar-nucleotide
      donor at 37 degrees C, followed by washing, addition of scintillation counting
      fluid, and measurement of radioactivity using a 96-well beta-counter.
      Glycopolymer construction and coating of the plastic plates, enzyme and substrate
      concentrations, and linearity with time were optimized using recombinant Core 2
      beta1-6-N-acetylglucosaminyltransferase (Core 2 GlcNAc-T). This enzyme catalyzes
      a rate-limiting reaction for expression of polylactosamine and the selectin
      ligand sialyl-Lewis(x) in O-glycans. A glycopolymer acceptor for beta1-6-N
      acetylglucosaminyltransferase V was also designed and shown to be effective in
      the solid-phase assay. In a high-throughput screen of a microbial extract
      library, the coefficient of variance for positive controls was 9.4%, and high
      concordance for hit validation was observed between the Core 2 GlcNAc-T solid
      phase assay and a standard solution-phase assay. The solid-phase assay format,
      which can be adapted for a variety of glycosyltransferase enzymes, allowed a 5-6
      fold increase in throughput compared to the corresponding solution-phase assay.

PMID- 10972140
TI  - Determination of constituents of sulphated proteoglycans using a methanolysis
      procedure and gas chromatography/mass spectrometry of heptafluorobutyrate
      derivatives.
AB  - A major impediment in the analysis of glycosaminoglycans is the difficulty to
      cleave quantitatively the glycosidic bonds because of the stabilisation of
      glycosidic bonds and of the relative instability of the liberated constituents.
      This manuscript describes a modified procedure of methanolysis in the presence of
      barium acetate, reducing the destruction of uronic acids and increasing the
      cleavage yield. The reaction products could be identified and analysed
      quantitatively by GC and GC/MS of the heptafluorobutyrate derivatives of O-methyl
      glycosides of monosaccharides (for keratan sulphate and chondroitin sulphate B),
      or as a mixture of O-methyl glycosides of monosaccharides and of disaccharides
      (for the other sulphated glycosaminoglycans). Quantitative molar ratio between
      the different monosaccharide constituents (including the linkage region
      constituents) could be obtained, even when proteoglycans also contain classical N
      glycans or O-glycans.

PMID- 10972141
TI  - Monosaccharide compositions of Danaus plexippus (monarch butterfly) and
      Trichoplusia ni (cabbage looper) egg glycoproteins.
AB  - Monosaccharide compositions of eggs from Danaus plexippus (monarch butterfly) and
      Trichoplusia ni (cabbage looper) were analyzed. Analyses were performed mainly
      with high performance anion exchange chromatography (HPAEC) using crude extracts
      of eggs or SDS-PAGE separated and PVDF-blotted protein bands. Man and GlcN were
      the major components in all cases, but low levels of Gal and Fuc were possibly
      present in some samples. Some T. ni egg glycoproteins even contained GalN.
      Although a peak comigrating with Neu5Ac could be detected with HPAEC-PAD or RP
      HPLC (fluorometry) after derivatization with 1,2-diamino-4,5-methylenedioxy
      benzene, the quantities were too small to be significant as an integral part of
      the analyzed glycoproteins. These data suggests that most of glycans on the
      glycoproteins are pauci-Man type N-glycans, but a small portion of N-glycan may
      be either hybrid type or complex type.

PMID- 10972142
TI  - Lectin histochemical localization of N- and O-linked oligosaccharides during the
      spermiogenesis of the urodele amphibian Pleurodeles waltl.
AB  - The aim of this work is the characterization of the glycoconjugates of the
      spermatids during the spermiogenesis of the testis of an urodele amphibian,
      Pleurodeles waltl, by means of lectins in combination with several chemical and
      enzymatic procedures, in order to establish the distribution of N- and O-linked
      oligosaccharides in these cells. The acrosome was the most relevant lectin
      labeled structure. The O-linked oligosaccharides contained DBA- and SBA-positive
      GalNAc, AAA-positive Fuc and PNA-positive Gal beta1,3GalNAc. Sialic acid was
      scarcely observed, the Neu5Ac alpha2,3Gal beta1,4GlcNAc sequence was found in N
      linked oligosaccharides. Additionally, N-linked oligosaccharides containing HPA
      positive GalNAc and AAA-positive Fuc were found. Moreover, with some lectins the
      acrosome showed a variable composition of the oligosaccharides in the different
      steps of the sperm maturation. Some residues were found only in the early steps
      in maturating acrosome, while others were in the later steps, showing that
      acrosomal glycoconjugates are modified during acrosome development in
      spermiogenesis. The changes observed during acrosome maturation suggest the
      existence of a predetermined pattern of storage of the acrosome components and a
      progressive compression of them.

PMID- 10972143
TI  - Overexpression of alpha2,3 sialyltransferase in neuroblastoma cells results in an
      upset in the glycosylation process.
AB  - Glycosylation is key posttranslational modification for membrane-bound and
      secreted proteins that can influence both the secondary structure and the
      function of the protein backbone. In order to investigate the effect of altered
      cellular glycosylation potential, we have generated a number of clonal cell lines
      over-expressing the alpha2,3(N) sialyltransferase enzyme (ST3N). In general,
      there was a decrease in total sialyltransferase (ST) enzyme activity in the
      clones transfected with the ST3N cDNA, with this decrease being inversely
      proportional to the quantity of the mRNA coding for the enzyme. The ST3N enzyme
      was, however, functional and there was an increase in both MAA lectin staining
      and the expression of polysialic acid, which is attached to the NCAM protein
      backbone primarily via an alpha2,3 linkage. These results suggest that the
      overexpression of a sialyltransferase may upset the sialylation potential of the
      cell.

PMID- 10972144
TI  - Deletion of A-antigen in a human cancer cell line is associated with reduced
      promoter activity of CBF/NF-Y binding region, and possibly with enhanced DNA
      methylation of A transferase promoter.
AB  - Employing blood group A- and A+ clones derived from the same parental colonic
      cancer cell lines, we studied the molecular mechanism of deletion/reduction vs.
      continuous expression of A antigen in A tumors, a crucial determinant of human
      tumor malignancy. A- transferase mRNA level in one of the A- clones (A- SW480)
      was undetectable, while that in A+ SW480 was strongly detectable by
      semiquantitative RT-PCR. Relatively lower (approximately 1/3) transcript level
      was detectable in another A- clone (A- HT29) in comparison to A+ HT29 by the same
      RT-PCR procedure, although none of these tumor cell lines showed detectable level
      of A transcript by Northern blotting or RNase protection methods. Therefore,
      subsequent studies were performed employing A- vs. A+ SW480 clones. Deletion of A
      transcript in A- cells was not due to gene deletion, since Southern blot analysis
      showed equal presence of genomic DNA regardless of A- vs. A+ (SW480 or HT29) or
      B+ (KATOIII) tumor cells. Two transcriptional control mechanisms leading to
      differences of A expression in SW480 cells are indicated. i. Luciferase assay in
      A- and A+ SW480 cells showed that promoter activities of segments of 5' flanking
      sequence of ABO gene reflected transcript levels in these cell lines. The
      enhancing activity of a 43 bp tandem repeat unit located between -3899 to -3618
      was reduced in A- compared to A+ cells. ii. Distinct differences in the pattern
      of CpG dinucleotide methylation were found in A- vs. A+ cells. Therefore, the
      methylation process of A promoter DNA may be another important factor controlling
      A activity in SW480 tumor cells. Since proliferation and motility of tumor cells
      are associated closely with A expression, transcription control mechanism for
      expression of A transferase as described above may be of crucial importance in
      defining human tumor malignancy.

PMID- 10972145
TI  - Detecting inflammation with 131I-labeled ornidazole.
AB  - The aim of this study was to demonstrate the accumulation of 131I-labeled
      ornidazole (131I-ORN) in experimental abscesses. 131I-ORN was prepared by
      electrophilic radioiodination of ORN, using radioiodide in the presence of
      Iodogen. An in vivo inflammation model was prepared by intramuscular injection of
      turpentine into the thigh of rabbits. Four days later 131I-ORN was intravenously
      administered to rabbits. Serial scintigrams were performed at different periods,
      using a Sophy DX Gamma Camera. 131I-ORN was visualized at 10 min after injection.
      131I-ORN was also administered intraperitoneally to rats with turpentine-induced
      inflammation, for quantitative biodistribution studies. Counts of selected
      tissues were taken by a NaI(Tl) scintillation detector (gamma counter) after rats
      were decapitated. The target-to-non-target muscle ratios were 2.5, 2.6, 2.9 and
      1.9 at 1, 3, 5 and 24 h, respectively.

PMID- 10972146
TI  - The quantification of technetium in generator-derived pertechnetate using ICP-MS.
AB  - Previous analytical methods employed to measure 99Tc:99mTc ratios in
      chromatographic 99mTc generators, derived from fission-based 99Mo, were limited
      in monitoring the ratios in low activity generators, over the extent of their
      elution regimes. For regulatory purposes, ICP-MS was employed to measure total
      technetium in generator eluates down to a level of 200 pg ml(-1) (200 ppt).
      Measured 99Tc:99mTc ratios compared very well with the theoretically computed
      values, ranging from 47:1 for a first elution of a generator with a long ingrowth
      time to 1.4:1 for the 17th elution of a generator with a short ingrowth time.

PMID- 10972147
TI  - Radiochemical separation of no-carrier-added 177Lu as produced via the
      176Yb(n,gamma)177Yb-->177Lu process.
AB  - The 176Yb(n,gamma)177Yb-beta(-)-->177Lu process was investigated to provide no
      carrier-added (nca) 177Lu. The radiochemical separation of the 177Lu from the
      macro-amounts of the ytterbium target based on the cementation process, i.e. the
      selective extraction of Yb by Na(Hg) amalgam from Cl-/CH3COO- electrolytes,
      followed by a final cation exchange purification. The cementation separation
      process provides a decontamination factor of Yb(III) of 10(4), the cation
      exchange purification adding a decontamination factor of > 10(2). The nca 177Lu
      is available in radiochemically pure form despite the chemical similarity of the
      lanthanides with 75 +/- 5% overall separation yield within 4-5 h. It can be used
      to synthesise nca 177Lu labelled radiotherapeuticals.

PMID- 10972148
TI  - Stereotactic dose planning system used in Leksell Gamma Knife model-B: EGS4 Monte
      Carlo versus GafChromic films MD-55.
AB  - The accuracy of the dose planning system (Leksell GammaPlan) used in Gamma Knife
      (model-B) radiosurgery was verified using both the GafChromic films MD-55
      (improved) and the EGS4 Monte Carlo technique. The Monte Carlo technique was
      employed to calculate the dose distribution along the x-, y- and z-axes when a
      single shot with opening of all 201 sources was delivered at the centre of a
      simulated water phantom with a diameter of 160 mm. Collimator helmets with
      different size of the Gamma Knife unit were verified. Good consistency (typical
      discrepancy less than 2%) was obtained between the results of Monte Carlo and
      GammaPlan. Small discrepancies, however, were obtained by GafChromic films.
      Discrepancies, as great as 10% when using the 4 mm collimator helmet, at the low
      percentage isodose curve along the z-axis of the measurement results were
      probably due to the small energy dependency of the GafChromic films. Significant
      discrepancies were not observed along x- and y-axes because such small
      discrepancies were easily over-washed by other gamma beams coming from the x- and
      y-directions. Similar results showing the discrepancies between the GafChromic
      films and GammaPlan were obtained when using the 8, 14 and 18 mm collimator
      helmets. However, the discrepancies along the z-axis became smaller as scattering
      effect increased when using larger collimator sizes. We suggest that the Monte
      Carlo technique should also be applied in stereotactic dose planning system
      verification as it is an ideal and reliable computational technique.

PMID- 10972149
TI  - Stability studies on (99m)technetium(III) complexes with tridentate/monodentate
      thiol ligands and phosphine ('3 + 1 + 1' complexes).
AB  - The preparation and characterisation of 3 + 1 + 1 technetium complexes of the
      general formula [Tc(SES)(RS)(PMe2Ph)] (SES = tridentate dithiol ligand, E = S, O,
      NMe; RSH = monothiol ligand) at the n.c.a. level is described. The Tc(III)
      complexes are prepared in a one-step procedure starting from pertechnetate in
      yields of 85-95% of radiochemical purity. A comparison of their chromatographic
      data with the fully characterised 99Tc complexes indicate the identity of the
      investigated compounds. Stability studies show that the 99mTc complexes undergo
      some alteration in solution. They are oxidised to the 3 + 1 oxotechnetium (V)
      complexes and/or decompose in aqueous solution. In challenge experiments
      performed with glutathione, exchange of the monothiolato ligand occurs in the
      same manner as known for the 3 + 1 complexes.

PMID- 10972150
TI  - Fabrication and tests of 3He and 2H targets for beam polarization measurement
AB  - 3He and 2H targets were fabricated through implantation of 3He and 2H ions in 0.2
      0.3 mm thick tantalum and titanium foils. The energy of 3He and 2H ions was 45
      100 and 78 keV, respectively. Ions beams with typical current of 90-300 microA
      were used for implantation. Stability tests of 3He and 2H targets were carried
      out by monitoring the yield of 3He(d, p)4He and 2H(d, p)3H reactions. For the 3He
      target, the reaction yield was stable for both tantalum and titanium foils but
      the most stabilized maximum yield was observed for the 100 keV tantalum target.
      In the case of 2H targets, the yield increased with increasing total dose
      implanted on the target.

PMID- 10972151
TI  - Radiolabeling of dextran with rhenium-188.
AB  - This study describes a method for the radiolabeling of dextran with rhenium-188
      (188Re). In nuclear oncology 188Re is very useful for therapeutic applications.
      Its nuclear characteristics allow radiotherapy and in situ monitoring of tumor
      uptake as well as dosimetry calculations. Consequently new compounds with this
      radiolabel are of general interest. Dextran was oxidized with sodium periodate
      yielding reactive aldehyde groups and subsequently reacted with cysteine. The
      linkage was stabilized by reducing the Schiff bases with sodium cyanoborohydride.
      The conjugate was then radiolabeled with 188Re by using 188Re-gluconate as the
      transchelator, labeling the free thiols. Synthesis and radiolabeling were done in
      the absence of oxygen. The labeling efficiency was 60-70% and the radiochemical
      purity > 95%. The in vitro stability study, using "cysteine challenge"
      demonstrated that 50% of the radiolabel was transcomplexed to the 100 mM cysteine
      solution (after 1 h incubation at 37 degrees C). However, at physiologic
      conditions and presence of an antioxidant good stability was achieved. The 188Re
      labeled dextran presented in this study provides a template with therapeutic and
      diagnostic potential in nuclear oncology, either alone for local treatment or as
      a backbone in a tumor specific conjugate for systemic treatment.

PMID- 10972152
TI  - A water-cooled spherical niobium target for the production of [18F]fluoride.
AB  - A new automated target system for the routine production of [18F]fluoride from
      (18)O-enriched water has been constructed. It consists of a small spherical
      niobium target chamber mounted into a special holder, which provides rapid
      cooling by water flow around the sphere. The target is irradiated with 21 MeV
      protons; the incident energy in the target chamber is 13 MeV. The system is
      operated without external over-pressure and has been tested for beam currents up
      to 50 microA. 95% of the theoretical yield of [18F]fluoride has been extracted
      and used for the synthesis of [18F]2-fluoro-2-deoxy-D-glucose.

PMID- 10972153
TI  - Radiocaesium and radiostrontium uptake by fruit bodies of Pleurotus eryngii via
      mycelium, soil and aerial absorption.
AB  - There has been an extraordinary increase in interest concerning the transfer of
      radioactive contamination to the fruit bodies of fungi since the Chernobyl
      nuclear power plant accident. These investigations, however, have focused
      exclusively on field studies aimed fundamentally at quantifying the behaviour of
      the radiocaesium component of the contamination. The results have shown great
      variability. As a contribution towards this body of knowledge, we have made a
      comparative study of the temporal evolution of the transfer of 85Sr and 134Cs via
      three routes of radioactive contamination--from the mycelium, from the surface
      layer of the soil, and directly onto the caps of the fruit bodies--for the
      saprophyte species, Pleurotus eryngii, under controlled laboratory conditions.
      The results indicate that the last of the above three uptake routes is the most
      efficient, and that the temporal evolution of the transfer is closely related to
      the radionuclide and the radioactive contamination route being considered.

PMID- 10972154
TI  - Evaluation of equivalent dose to working staff with oxygen-15-water in positron
      emission tomographic studies.
AB  - With its short physical half-life and allowing for higher dosage injections,
      oxygen-15 labeled water has become increasingly important in many clinical
      applications. However, the use of oxygen-15 labeled water could potentially
      result in radiation exposures to working staff exceeding regulatory limits. In
      this study, thermoluminescent dosimeters (LiF-100H) were attached at various
      parts of the body to measure the accumulated equivalent doses of a physician and
      to evaluate the radiation risk to the sensitive organs which could receive as
      many as 10 intravenous injections of (15)O-water for each subject studied. The
      results showed that during the injections, the hands of a physician received the
      highest dose, which was about 25.8 times that of the routine chest X-ray dose. If
      protective shieldings were provided during injection, about 83% of the dose could
      be effectively reduced. Even without any protective shielding, the estimated
      maximum dose to the physician was still within the regulatory limit, 50 mSv/year,
      suggested by ICRP 60. In conclusion, reducing excess radiation exposure to
      workers, by minimizing the time spent in close contact with patients, increasing
      the distance from the source and providing suitable protective shielding would be
      the most effective approach.

PMID- 10972155
TI  - Half-life and X-ray emission probabilities of 55Fe.
AB  - The X-ray emission probabilities of the Mn-K(alpha) and Mn-K(beta) radiation in
      the decay of 55Fe were measured with a calibrated Si(Li) spectrometer, resulting
      in 0.245(7) and 0.0338(9), respectively. A half-life of 1003.5(21) day was
      measured using the same detector.

PMID- 10972156
TI  - Estimating the radon emanation coefficient from crystalline rocks into
      groundwater.
AB  - A simple method is proposed to estimate the coefficient of radon emanation from
      crystalline rocks into underground waters. In these cases, the crystalline rock
      seems as both the source and the reservoir of the radon. The calculations are
      based on a formula proposed by Mache for determining the concentration of radon
      in underground waters. Due to the inaccuracy of estimating some parameters (e.g.
      porosity), the results have a significant error. The advantage of this method is
      its simplicity and the possibility of obtaining results in a relatively short
      time. The estimated values of the emanation coefficient for selected crystalline
      rocks of the Sudety Mountains (SW Poland) vary from 7 to 41%, and after
      considering the error resulting from the estimation of rock porosity, saturation
      and density, the values range from 5 to 60%. The highest values of emanation
      coefficient (41, 33 and 21%) have been obtained for rocks in areas of tectonic
      dislocations and the lowest ones are for rocks outside dislocation zones (9 and
      7%). The calculations imply that the emanation coefficient of rocks may have a
      greater influence on radon concentration in underground waters than the contents
      of radium in the reservoir rocks.

PMID- 10972157
TI  - Quality assessment of heparin coatings by their binding capacities of coagulation
      and complement enzymes.
AB  - In vitro testing of blood contacting materials before clinical application is
      generally advisable. Four heparin coatings from different manufacturers were
      tested for adsorbed proteins and soluble activation markers. The surface with the
      highest antithrombin, thrombin, high-molecular-weight-kininogen (HMWK) and the
      lowest fibrinogen binding capacity (Carmeda, Medtronic) showed significantly
      lower levels of granulocytes and platelet activation (beta-TG, PMN-elastase
      release). No statistically significant differences in soluble markers of the
      coagulation system could be detected (F1 + 2, TAT). Interestingly, complement
      activation (TCC) was significantly reduced within the group of the lowest
      adsorption of the complement factor C3. Our data demonstrate that there is a
      relation between the binding affinity of proteins (C1-inhibitor, C3-complement)
      and the consecutive changes in complement activation (TCC). Therefore, measuring
      adsorbed proteins on artificial surfaces is a suitable, sensitive and very
      reproducible method for assessing the thrombogenicity of biomaterials.

PMID- 10972158
TI  - In vitro release behavior of dextran-methacrylate hydrogels using doxorubicin and
      other model compounds.
AB  - In vitro drug release behavior of doxorubicin, Alizarin Red S, FITC-dextran from
      photocross-linked dextran-methacrylate hydrogel was studied. The effects of pH of
      media, degree of substitution (DS) of dextran-methacrylate hydrogel, and
      molecular weight of model compounds on their release profiles were investigated.
      Each model compound was successfully incorporated into dextran-methacrylate
      hydrogel matrix through photopolymerization of the hydrogel precursor. Delayed
      release of model compounds was observed with these hydrogels having a higher DS.
      Doxorubicin and Alizarin Red S showed pH-dependent release behavior because of
      the presence of ionizable groups in their structure. Different types of
      ionization of doxorubicin and Alizarin Red S resulted in more release into an
      acidic or alkaline media. As molecular weights of drugs increased, the total
      amount of released drug at the end of 240 hrs decreased significantly and reached
      a minimum level as the MW of drugs reached about 10,000. Release of these three
      model compounds followed simple Fickian diffusion at an early stage of release,
      i.e., cumulative release of model compounds was proportional to the square root
      of time. Dextran-methacrylate hydrogel effectively delayed and controlled the
      release of anticancer antibiotics, doxorubicin.

PMID- 10972159
TI  - Uniaxial and biaxial tensile strength of calf pericardium used in the
      construction of bioprostheses: biomaterial selection criteria.
AB  - Using morphological and mechanical criteria and applying a method involving
      paired samples that is widely employed in epidemiology, we obtained an excellent
      prediction of the mechanical behavior of the calf pericardium used in the
      construction of cardiac bioprostheses. The method of selection employed in this
      study may be a highly useful tool for guaranteeing the mechanical resistance of
      calf pericardium, with a very low level of error.

PMID- 10972160
TI  - Polymers for use in controlled release systems: the effect of surfactants on
      their swelling properties.
AB  - The effect of an ampholytic surfactant on the swelling properties of polymeric
      materials was studied, using various swelling liquids. Tablets were prepared
      consisting of hydroxypropyl methylcellulose, poly(oxyethylene) and sodium
      alginate. Tego betain was the non-ionic surfactant used as an additive in a
      series of samples made of the above polymers. Those tablets were immersed in
      distilled water, phosphate buffer and 0.1 N HCl, and their weight uptake was
      recorded as a function of time, in order to assess the swelling process.
      Measurements of the contact angle of the above systems were also carried out for
      estimating their wetting properties. The results of this study showed a
      selectivity among polymers, surfactant and surrounding liquid. Clearly, an
      enhancement of the swelling capacity of hydroxypropyl methylcellulose tablets due
      to the surfactant was recorded. An unclear effect was observed in the case of
      poly(oxyethylene), whereas for sodium alginate, the dominant factor is its water
      solubility that controls swelling behaviour.

PMID- 10972161
TI  - Mechanism of antihypertensive effect of dietary potassium in experimental volume
      expanded hypertension in rats.
AB  - Dietary potassium supplementation lowers blood pressure (BP) and attenuates
      complications in hypertensive subjects, particularly those with the low renin
      volume expanded (LRVE) variety. We and others have shown that the plasma level of
      a digitalis like substance (DLS) is elevated in this type of hypertension. We
      therefore, examined the effect of increases in dietary potassium on the plasma
      level of endogenous DLS, myocardial and renal Na+, K+-ATPase (NKA) activities,
      BP, and renal excretory function in reduced renal mass (RRM)-salt hypertension in
      the rat, a classical model of LRVE hypertension. 70% RRM rats were divided in 4
      groups, namely those consuming: 1) a sodium free and normal potassium (1.3% as
      KCl) diet (RRM-0 Na), 2) a normal sodium and normal potassium diet (RRM-NaK), 3)
      a normal sodium and high potassium (2 X normal) diet (RRM-Na2K), and 4) a normal
      sodium and 4 times normal potassium diet (RRM-Na4K). At the end of 4 weeks of
      dietary treatment, direct BP was recorded, plasma level of DLS determined by
      bioassay and with a radioimmunoassay for digoxin (DIF) and myocardial and renal
      NKA activities were measured. As expected, compared to RRM-0Na rats, RRM-NaK rats
      developed hypertension. BP increased significantly less in RRM-Na2K, whereas BP
      did not increase in RRM-Na4K rats. Hypertension in RRM-NaK rats was associated
      with an increase in plasma DLS and DIF and decrease in renal and myocardial NKA
      activities. DLS was increased (DIF was not changed) and myocardial NKA also
      decreased in rats consuming double potassium. However, quadrupling potassium in
      the diet (RRM-Na4K) normalized DLS and DIF and increased myocardial and renal NKA
      activities, compared to RRM-0Na rats. Also compared to RRM-0Na, water
      consumption, urinary volume excretion, sodium, and potassium increased in the
      other 3 groups, more so in RRM-Na4K rats. These data show that quadrupling the
      potassium in the diet prevents the BP increase in RRM rats and this is associated
      with diuresis/natriuresis and normalization of DLS, perhaps because the
      diuresis/natriuresis normalizes blood volume.

PMID- 10972162
TI  - Effect of acute intravenous ace-inhibition on the intrarenal doppler flow
      characteristics in hypertensive patients with and without unilateral renal artery
      stenosis.
AB  - Assessment of intrarenal doppler signals is of particular importance in screening
      for renal artery stenosis. We studied the effect of acute ACE-inhibition (1,25 mg
      enalaprilate i.v.) on intrarenal resistive indices in 10 hypertensive patients
      with unilateral renal artery stenosis versus 10 patients with essential
      hypertension. Any changes limited to poststenotic vessels could possibly improve
      the diagnostic value of duplex sonography. After ACE-inhibition a significant
      fall of the intrarenal Resistive Index occurred in both patient groups. In cases
      of unilateral renal artery stenosis we saw a tendency to an increased side
      difference of the Resistive Index due to a greater fall on the poststenotic side.
      Therefore a clear advantage of duplex scanning after acute ACE-inhibition due to
      a limited effect of enalaprilate on poststenotic vessels was not found. The
      results suggest that the vascular resistance and not only the degree of renal
      artery stenosis is of significance for the characteristics of the doppler signal.

PMID- 10972164
TI  - Plasma tumor necrosis factor alpha levels and insulin sensitivity in hypertensive
      subjects.
AB  - Recent studies have shown that tumor necrosis factor-alpha (TNFalpha), secreted
      by macrophage, adipocyte and muscle cells, are associated with insulin resistance
      syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density
      lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma
      TNFalpha levels relate to insulin resistance syndrome in subjects with essential
      hypertension who are also characterized by an insulin resistance state. We
      recruited 85 nondiabetic subjects (45 men and 40 women) with essential
      hypertension and 85 nondiabetic subjects who were matched for age, sex and body
      mass index (BMI) to determine their fasting plasma glucose, insulin and
      lipoprotein concentrations, their glucose and insulin responses to an oral
      glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin
      and TNFalpha levels were measured by radioimmunoassay and chemiluminescent enzyme
      immunometric assay respectively. Total body fat mass was assessed by the
      bioelectrical impedance method. The results showed that fasting plasma leptin
      levels were similar between hypertensive and normotensive subjects (7.9 +/- 0.6
      vs 7.4 +/- 0.7 ng/ml, p=0.190). Fasting plasma TNFalpha concentrations were not
      different between subjects with hypertension and normotension (10.5 +/- 0.5 vs
      9.8 +/- 0.4 pg/ml, p=0.360). Fasting plasma TNFalpha concentrations were not
      different across three subgroups of the insulin resistance both in hypertensive
      patients (8.4 +/- 0.4 vs. 10.9 +/- 1.6 vs. 9.9 +/- 1.0 pg/ml, p=0.297) and
      normotensive subjects (9.2 +/- 0.7 vs. 9.3 +/- 0.9 vs. 9.7 +/- 0.9 pg/ml,
      p=0.875). Fasting plasma TNFalpha values showed significantly positive
      correlations with triglyceride concentrations (p<0.03) but negative correlation
      with HDL cholesterol concentrations (p<0.04) in normotensive but not in
      hypertensive individuals. These relations persisted even after adjustment for BMI
      and total fat mass. In conclusion, our data indicated that circulating levels of
      TNFalpha did not differ between hypertensive subjects and normotensive controls.
      Plasma TNFalpha concentrations correlated positively with fasting plasma
      triglyceride levels and negatively with HDL cholesterol concentrations in
      normotensive but not in hypertensive subjects. The influence of TNFalpha on
      carbohydrate and lipoprotein metabolism in hypertensive patients deserves further
      investigations.

PMID- 10972163
TI  - Event-related potentials in the elderly with new mild hypertension.
AB  - Hypertension is a risk factor for cerebrovascular diseases (CVD) and cognitive
      impairment and the relative risk of CVD at every level of blood pressure (BP) is
      greater among the elderly. We submitted 20 elderly affected by new mild
      hypertension and 10 elderly normotensives to 24-hour ambulatory BP monitoring
      (ABPM), to evaluate their cognitive state using the Mini-Mental-State-Examination
      and to the recording of related acoustic evoked potentials (P300 and N2). We did
      not find significant differences for P300 latency between hypertensives and
      normotensives, while N2 latency recording showed a statistically significant
      protracted value in elderly hypertensives. In these patients we found a
      significant correlation between the N2 latency and systolic blood pressure values
      recorded by ABPM. These results demonstrated early functional alterations of
      cognitive state in elderly hypertensives, that are related to systolic blood
      pressure and future data might point to an earlier use of therapy.

PMID- 10972165
TI  - Daily exercise attenuated the sympathetic component of the spontaneous arterial
      baroreflex control of heart rate in hypertensive rats.
AB  - The influence of daily spontaneous running on the sympathetic and parasympathetic
      components of the spontaneous arterial baroreflex control of heart rate was
      examined in 22 female spontaneously hypertensive rats [12 sedentary and 10 daily
      spontaneous running]. Following 8 weeks of sedentary control or daily spontaneous
      running, animals were chronically instrumented with an arterial catheter. Daily
      spontaneous running resulted in an increased heart weight/body weight ratio (5.2
      +/- 0.27 vs 4.3 +/- 0.01 g/kg) and a resting bradycardia (321+/- 8 bpm vs 360 +/-
      6). The spontaneous changes in arterial pressure and the reflex responses of
      heart rate were examined under three experimental conditions: 1) pre-blockade, 2)
      following beta1-adrenergic receptor blockade, and 3) following muscarinic
      cholinergic receptor blockade. Daily spontaneous running attenuated the
      spontaneous gain of the arterial baroreflex control of heart rate (56%). After
      muscarinic-cholinergic receptor blockade, the spontaneous gain remained reduced
      in daily spontaneous running rats (57%). In contrast, after beta1-adrenergic
      receptor blockade the spontaneous gain was not different between sedentary
      control and daily spontaneous running animals. Results demonstrate that daily
      spontaneous running decreased the sympathetic component resulting in an
      apparently greater influence of the parasympathetic component on the spontaneous
      arterial baroreflex control of heart rate.

PMID- 10972166
TI  - Autonomic and endothelial dysfunction in experimental diabetes.
AB  - The effect of streptozotocin induced diabetes on autonomic regulation of heart
      rate and endothelial function was examined in Sprague-Dawley rats. Weanling rats
      (3-4 weeks of age) of either sex were randomly assigned to a non-diabetic (male
      5, female 6) or diabetic (male 4, female 5). Diabetes was induced with a single
      intraperitoneal (IP) injection of streptozotocin (STZ, 100 mg/kg). Nondiabetic
      rats received an IP injection of saline. Eight weeks after injection, rats were
      chronically instrumented with a left jugular venous catheter and a left carotid
      arterial catheter. After recovery (5 days) cardiac sympathetic tonus,
      parasympathetic tonus and intrinsic heart rate were determined. On an alternative
      day, the pressor response to nitric oxide synthase inhibition (NOS-X) was
      determined in areflexic rats. Cardiac sympathetic tonus (72 +/- 13 vs. 41 +/- 7),
      parasympathetic tonus (-51 +/- 10 vs. -22 +/- 7), and intrinsic heart rate (368
      +/- 6 vs. 292 +/- 9), were reduced in diabetic rats. Furthermore, diabetic rats
      had a smaller pressor response (A33 +/- 7 vs. A66 +/- 5) to NOS-X. These results
      document impaired autonomic control of heart rate and endothelial dysfunction in
      8-week streptozotocin induced diabetic rats.

PMID- 10972167
TI  - Dopamine inhibits na,h-exchanger via D1-like receptor-mediated stimulation of
      protein kinase a in renal proximal tubules.
AB  - Dopamine causes natriuresis and diuresis via activation of D1-like receptors
      located in the renal proximal tubules. It is reported that this response to
      dopamine results from the inhibition of Na,H-exchanger and Na,K-ATPase. Earlier
      studies have suggested a role of protein kinase A (PKA) in the inhibition of Na,H
      exchanger, however, the effect of dopamine or the dopamine receptor subtype
      responsible for the stimulation of PKA has not been reported. Present study was
      designed to examine the effect of dopamine and D1-like receptor agonist, SKF
      38393, on the stimulation of PKA activity in rat renal proximal tubules. Dopamine
      and SKF 38393 (1 nM - 1 microM) caused stimulation of PKA activity, an effect
      which was antagonized by a D1-like receptor antagonist, SCH 23390 (10 microM).
      Stimulation of PKA activity was also seen with forskolin and di-butyryl cAMP. We
      also observed that dopamine and SKF 38393 inhibited Na,H-exchanger activity in
      the proximal tubules. This response was blocked by SCH 23390 and Rp-cAMPS
      triethylamine, a selective inhibitor of PKA. Similarly, forskolin and di-butyryl
      cAMP inhibited Na,H-exchanger activity. The data provide direct evidence showing
      that dopamine, through the activation of D1-like receptors stimulates PKA
      activity which in turn inhibits Na,H-exchanger in the proximal tubules.

PMID- 10972168
TI  - Chronic inflammatory bowel disease and pregnancy.

PMID- 10972169
TI  - Long-term follow-up of patients with jejunal pouch reconstruction after total
      gastrectomy. A randomized prospective study.
AB  - BACKGROUND: Fifty-one patients were operated on during 1988-1992 and randomized
      after total gastrectomy to one of two reconstruction types. Twenty patients with
      jejunal pouch reconstruction and 14 patients with Roux-en-Y reconstruction (67%
      of all) survived at least 3 years after total gastrectomy. We studied symptoms,
      eating capacity, and nutrition in these patients during the clinical follow-up;
      21 patients were assessed by mail questionnaire 8 years after total gastrectomy.
      METHODS: Postoperative symptoms, number of meals, and eating capacity were
      assessed by standard questionnaire during 3 years' follow-up. Weight loss and
      nutritional laboratory variables were measured, and upper intestinal endoscopy
      with biopsy was performed during the follow-up. Eight years after the operation
      symptoms, ability to eat, and number of meals consumed were studied by means of a
      mail questionnaire. RESULTS: Three years postoperatively dumping (64% compared
      with 10%, P < 0.05) and early satiety (86% compared with 5%, P < 0.05) were
      commoner in the Roux-en-Y group. In the pouch group eating capacity was better
      (96% of normal compared with 67%, P < 0.05), and the patients ate fewer meals per
      day (mean, 2.7 versus 5.3, P < 0.05) at 3 years. Mean weight loss at 3 years was
      9.9 kg in the Roux-en-Y group compared with 1.5 kg in the pouch group (P < 0.05).
      25 (OH) vitamin D concentration tended to be higher in the pouch group (47.3
      nmol/l compared with 33.9 nmol/l). In the Roux-en-Y group serum alkaline
      phosphatase activity increased significantly during the 3 postoperative years
      (from mean 163 U/l to 248 U/l, P < 0.01) and tended to be higher (248 U/l
      compared with 216 U/l in the pouch group). None of the patients developed
      oesophagitis or pouchitis during the follow-up. One patient developed a bezoar in
      the pouch 5 years after gastrectomy. CONCLUSIONS: Pouch reconstruction after
      total gastrectomy is associated with diminished postoperative symptoms, better
      eating capacity, and decreased weight loss compared with Roux-en-Y
      reconstruction. Jejunal pouch reconstruction is thus the recommended surgical
      method after total gastrectomy.

PMID- 10972170
TI  - Effects of phorbol ester treatment on dibutyryl cyclic adenosine-5' monophosphate
      and carbachol-stimulated aminopyrine accumulation in isolated rat parietal
      cells.
AB  - BACKGROUND: The functional role of the intracellular diacylglycerol/protein
      kinase C second-messenger pathway in the regulation of gastric acid secretion and
      the effects on the involved inositotrisphosphate/Ca2+/calmodulin system are not
      well understood, and contradictory data have been reported. We therefore
      evaluated the effects of phorbol ester treatment (tetradecanoylphorbol-12,13
      acetate (TPA)) on dibutyryl cyclic adenosine-5' monophosphate (dBcAMP)- and
      carbachol-stimulated aminopyrine (AP) accumulation in comparison with
      intracellular alterations of the phospholipase C/inostol phosphate signal
      transduction pathway in isolated rat gastric parietal cells. METHODS: [14C]AP
      accumulation was determined as an indirect measure of gastric acid secretion.
      Inositolphosphate second-messenger activation was investigated with
      [3H]inositolmonophosphate release in [3H]-myoinositol prelabeled rat gastric
      parietal cells. RESULTS: TPA at a low concentration of 5 nM caused a small (45%)
      but significant increase in carbachol (0.1 mM)-stimulated AP accumulation, which
      was dose-dependently inhibited by higher concentrations of TPA with corresponding
      shifts in the dose-response curve for carbachol-stimulated AP accumulation. AP
      uptake stimulated by dBcAMP (0.1 mM) and the synergistic stimulatory effect
      induced by carbachol together with dBcAMP were inhibited by TPA at all
      concentrations investigated. In the presence of increasing concentrations of the
      calcium ionophore ionomycin (10(-8)-10(-5) M) TPA at 5 nM increased AP
      accumulation (AP ratio was 4.02 with 5 nM TPA versus 1.23 in the absence of TPA;
      P < 0.05), indicating that phorbol ester stimulates AP uptake in rat parietal
      cells. Simultaneous investigation of [14C]AP accumulation and [3H]inositol
      monophosphate release showed that inhibitory effects of TPA on carbachol- and
      carbachol plus dBcAMP-stimulated cells are mediated by an inhibition of the
      receptor/G-protein/phospholipase C interaction, leading to a reduction of
      inositolphosphate release. The costimulation of rat parietal cells with dBcAMP,
      ionomycin, and TPA (5 nM) did not reproduce the synergistic effects of carbachol
      together with dBcAMP on AP accumulation, suggesting that carbachol-stimulated AP
      uptake seems to be additionally mediated by a still unknown pathway independent
      of intracellular calcium release or protein kinase C activation.

PMID- 10972171
TI  - Helicobacter pylori infection reduces intraluminal nitric oxide.
AB  - BACKGROUND: Nitric oxide (NO) plays an important role in gastrointestinal mucosal
      protection. We have previously shown that Helicobacter pylori infection is
      associated with a lower concentration of NO in the human stomach. The aim of this
      study is to explore the pathogenesis of this finding using an animal model.
      METHODS: Mongolian gerbils were divided into four groups: H. pylori-negative and 
      positive, each with and without the intraperitoneal addition of superoxide
      dismutase (SOD). Intraluminal NO and serum nitrate were measured by using a
      chemiluminescence system. Inducible nitric oxide synthase (iNOS) levels in
      gastric mucosa were measured by using the NOSdetect Assay Kit. RESULTS: iNOS
      levels in H. pylori-positive gerbils were significantly greater than in those
      without infection. Intraluminal NO levels in H. pylori-positive gerbils were
      significantly lower than those in H. pylori-negative ones and increased after SOD
      administration. Serum nitrate levels in H. pylori-positive gerbils were
      significantly greater than those in H. pylori negative ones and decreased after
      SOD administration. CONCLUSIONS: The low level of NO in the gastric lumen in H.
      pylori infection is likely a result of superoxide production related to H. pylori
      induced inflammation.

PMID- 10972172
TI  - Transfer of metronidazole to gastric juice: impact of Helicobacter pylori
      infection and omeprazole.
AB  - BACKGROUND: The effects of Helicobacter pylori infection associated with
      inhibition of gastric acid secretion on the distribution of medications used for
      H. pylori eradication are poorly understood. The aim of this study was to
      investigate the effects of a 7-day administration of 20 mg omeprazole on the
      transfer of metronidazole from plasma to the gastric juice of individuals with
      and without H. pylori infection. METHODS: Fourteen H. pylori-positive and 14 H.
      pylori-negative male volunteers were enrolled in a study with an open,
      randomized, two-period crossover design with a 21-day washout period between
      phases. Plasma, salivary, and gastric juice concentrations of metronidazole in
      subjects with and without omeprazole treatment were measured with reversed-phase
      high-performance liquid chromatography/liquid chromatography. RESULTS:
      Metronidazole peak concentration (Cmax) was similar in plasma and saliva and was
      approximately threefold higher in gastric juice in all groups. Omeprazole
      treatment increased gastric pH and did not affect metronidazole Cmax or the time
      required for this to be reached (tmax) in plasma, saliva, or gastric juice.
      However, omeprazole significantly reduced metronidazole transfer from plasma to
      gastric juice in H. pylori-positive but not H. pylori-negative subjects, as shown
      by statistical analysis of AUC(0-2 h). CONCLUSION: Short-term treatment with
      omeprazole in H. pylori- positive volunteers reduces the amount of metronidazole
      transferred from plasma to gastric juice. This seems to occur in a pH-independent
      form.

PMID- 10972173
TI  - Mechanical properties of the gastro-esophageal junction in health, achalasia, and
      scleroderma.
AB  - BACKGROUND: Manometric assessment of the gastro-esophageal junction (GEJ) is
      deceptive in that ignores key dynamic properties of the junction, such as
      resistance to flow and compliance. Our aim was to investigate the mechanical
      properties of the GEJ comprising intraluminal pressure (measured by manometry),
      resistance to flow and compliance (measured by resistometry). METHODS: We studied
      8 healthy subjects, 11 patients with achalasia and 11 patients with scleroderma.
      We used a pneumatic resistometer, previously developed and validated in our
      laboratory. The resistometer consists of a flaccid polyurethane 5-cm cylinder
      connected to an electronically regulated nitrogen-injection system; the
      instrument records nitrogen flow through the cylinder while maintaining a
      constant pressure gradient between its proximal and distal ends. By placing the
      cylinder successively in the proximal stomach and along the GEJ we measured the
      GEJ-gastric resistance gradient (GEJ resistance minus gastric resistance) and
      were able to calculate the cumulative resistance (sum of resistance exerted at
      each pressure level), peak resistance (at any injection pressure), nil resistance
      point (injection pressure in mmHg at which GEJ resistance equals gastric
      resistance), and compliance slope (flow/pressure relationship). RESULTS: We found
      that GEJ resistance to flow (cumulative resistance, peak resistance, and nil
      resistance point) is significantly increased in achalasia and decreased in
      scleroderma (P < 0.05 versus health) while GEJ compliance is diminished in
      achalasia (P < 0.05 versus health) and normal in scleroderma. CONCLUSION:
      Achalasia is a disease characterized by increased GEJ resistance and rigidity. By
      contrast, although scleroderma is characterized by decreased GEJ resistance, GEJ
      compliance may be normal.

PMID- 10972174
TI  - Treatment of enterotoxigenic and enteropathogenic Escherichia coli-induced
      diarrhoea in children with bovine immunoglobulin milk concentrate from
      hyperimmunized cows: a double-blind, placebo-controlled, clinical trial.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic
      Escherichia coli (EPEC) are important causes of diarrhoea in young children and
      are associated with significant mortality rates. Passive immunization with
      antibodies from immunized cows has previously been shown to be effective as
      prophylaxis against E. coli-induced diarrhoea and therapeutically against
      rotavirus and cryptosporidia-induced diarrhoea. METHODS: We tested the
      therapeutic efficacy of an oral bovine immunoglobulin milk concentrate (BIC) from
      cows hyperimmunized with ETEC and EPEC strains, in a randomized, placebo
      controlled study in children with E. coli-induced diarrhoea. Eighty-six children
      between 4-24 months of age attending the International Centre for Diarrhoeal
      Disease Research, Bangladesh (ICDDR, B) with E. coli-induced diarrhoea (63
      EPEC/ETEC and 23 with other diarrhoeagenic E. coli) were randomly assigned to
      receive orally administered BIC (20 g) containing anti-ETEC/EPEC antibodies or a
      placebo preparation daily for 4 consecutive days. Daily stool output, intake of
      oral rehydration solution (ORS), stool frequency, and presence of diarrhoeagenic
      E. coli strains in the stool were monitored for 4 days. RESULTS: Children in the
      treatment group tolerated the BIC with no side effects. There were no significant
      differences between the two groups with regard to ORS intake, stool output,
      frequency of diarrhoea, or clearance of pathogen. Nor was there any significant
      alteration in the duration of diarrhoea. CONCLUSIONS: In contrast to the
      prophylactic efficacy of anti-E. coli BIC and the therapeutic efficacy of a
      similarly prepared anti-rotavirus BIC, antibodies from hyperimmunized cows appear
      to have no significant therapeutic benefit in the treatment of acute diarrhoea
      due to EPEC/ETEC.

PMID- 10972175
TI  - Does increased crypt cell proliferation impair cholesterol absorption after
      proximal gut resection?
AB  - BACKGROUND: The effects of proximal small-bowel resection on absorption and
      synthesis of cholesterol are unclear. METHODS: To study cholesterol absorption
      and synthesis after proximal gut resections of variable length, plasma plant
      sterols, cholestanol, and cholesterol precursors were measured 1 and 2 months
      after 50% and 75% proximal small-bowel resection or transection. To examine the
      effect of increased crypt cell proliferation and brush border development on
      cholesterol absorption, the results were related to the mucosal morphology, crypt
      cell proliferation, and disaccharidase activities of the remaining small bowel.
      RESULTS: Campesterol levels in proportion to cholesterol decreased markedly more,
      and those of cholestanol markedly less, than would be expected simply due to the
      amount of proximal small intestine removed, whereas sitosterol proportions
      decreased in proportion to the length of gut resection. Campesterol proportions
      markedly (P = 0.06) increased between 1 and 2 months after 50% resection but
      remained unchanged after 75% resection. Crypt cell proliferation was only
      increased in the 75% resection group (P < 0.05). The longer the proximal gut
      resection, the lower was the mucosal enzyme activity. Both resection groups
      showed increased plasma cholesterol precursor proportions and crypt depth (P <
      0.05), whereas villus height remained unchanged. After massive proximal resection
      campesterol and sitosterol proportions were inversely related to crypt cell
      proliferation (r = -0.86-0.83, P < 0.01). CONCLUSIONS: Increased crypt cell
      proliferation activated by massive proximal gut resection may act as a previously
      unrecognized factor in aggravating cholesterol malabsorption and retarding its
      recovery during the early postoperative period. These findings warrant further
      investigation.

PMID- 10972176
TI  - High intraluminal fluid flow increases intestinal IgA output.
AB  - BACKGROUND: Stool IgA output in normal stool or chronic diarrhoea is a fraction
      of that recorded in high-output watery diarrhoea due to cholera. We hypothesized
      that high intestinal fluid flow leads to increased IgA output, and this is not a
      consequence of reduced degradation/reabsorption. METHODS: Daily intestinal
      outputs of IgA and other secretory and non-secretory proteins were measured in
      stool from 14 volunteers with ileostomies and compared with the output during
      whole-gut lavage, a whole-gut perfusion system. RESULTS: Output into whole-gut
      lavage was significantly higher for all the proteins (P=0.02 to 0.001). Median
      IgA output into ileostomy effluent (IE) was 3.6 mg/kg/day compared with 26
      mg/kg/day into whole-gut lavage fluid (WGLF). Thus IgA recovery in stool was only
      12.7% of the amount in corresponding WGLF. Similar results were found for other
      proteins: specific IgA and IgM antibodies (5.4%-20.3%), IgM (42.4%), IgG (8.9%),
      and albumin (9.3%). Six subjects with IE water content >92% had increased
      recovery of IgA compared with eight with <92% water. In vitro, experiments
      predict that degradation of IgA within the small bowel results in 80% remaining
      compared with the 12.7% measured in vivo. CONCLUSIONS: Our data show that high
      intraluminal fluid flow increases the intestinal output of IgA and other
      proteins, and this is not a consequence of reduced degradation/reabsorption in
      the colon or small bowel. This increased protein output may be a non-specific
      response in the early stages of acute diarrhoea.

PMID- 10972177
TI  - Antiendomysium versus antigliadin antibodies in screening the general population
      for coeliac disease.
AB  - BACKGROUND: It has recently been shown that mass screening for coeliac disease,
      using either the serum antigliadin (AGA) or antiendomysium antibodies (EMA) as
      screening test, can detect large numbers of cases that had escaped clinical
      diagnosis. The influence of the diagnostic algorithm on the results of the
      coeliac screening has not yet been evaluated. Our aim was to compare the validity
      of the AGA and the EMA protocols in 2096 students living in northwest Sardinia,
      who took part in a serologic screening for coeliac disease. METHODS: The sample
      included 2096 of 2345 eligible students (89%) aged 11-15 years who underwent
      serum IgG AGA, IgA AGA, and IgA EMA determinations. Total serum IgA level was
      measured in sera showing isolated IgG AGA positivity. Subjects showing at least
      one of the following: a) EMA positivity, b) IgA AGA positivity, or c) IgG AGA
      positivity and IgA deficiency (<5 mg/dl) were asked to submit to a small
      intestinal biopsy. RESULTS: The prevalence of coeliac disease was 19 (16 showing
      typical enteropathy, 1 potential case, and 2 known cases) of 2096 (0.91%; 95%
      confidence interval = 0.50-1.31). Seventeen small-intestinal biopsy specimens
      were needed to confirm 16 cases of manifest coeliac disease (positive predictive
      value (PPV) = 94%) by the EMA protocol, whereas the AGA protocol required 21
      biopsy specimens for 12 cases of coeliac disease (PPV = 57%). None of six IgA
      deficient, IgG AGA-positive cases detected by the AGA protocol also had coeliac
      disease. CONCLUSIONS: The EMA protocol is superior to the AGA protocol for mass
      screening of coeliac disease because of higher sensitivity, decreased need for
      intestinal biopsy, and possibility to detect potential cases of coeliac disease.

PMID- 10972178
TI  - Identification of cells responding to vasoactive intestinal peptide by measuring
      intracellular cyclic adenosine monophosphate in human colonic mucosa.
AB  - BACKGROUND: Although there is great deal of evidence suggesting that vasoactive
      intestinal peptide (VIP) has immunomodulating effects on human colonic lamina
      propria mononuclear cells (LPMC), it remains unclear which type of cell carries
      functional VIP receptors. In this study we investigated the presence of
      functional VIP receptors by measuring intracellular cyclic adenosine
      monophosphate (cAMP) in isolated epithelial cells, bulk LPMC, T cells, and
      macrophages in human colonic mucosa. METHODS: Epithelial cells and LPMC were
      isolated from non-pathologic segment of colonic mucosa of surgical specimens from
      five patients with colonic cancer. Mucosal T cells and macrophages were further
      isolated from LPMC. Each cell population was cultured with various concentration
      of VIP for 60 min at most. Then, intracellular cAMP was extracted and measured by
      enzyme-linked immunoassay. RESULTS: When isolated epithelial cells were examined,
      VIP increased intracellular cAMP in a dose-dependent fashion, as observed in HT
      29 cells used as a positive control. In contrast, the concentration of cAMP was
      essentially stable in response to VIP when isolated LPMC were examined. This was
      the case even when separated T cells and macrophages were individually
      investigated. To evaluate the possible effects of enzyme digestion for LPMC
      isolation on the VIP response. HT-29 cells were precultured with collagenase and
      deoxyribonuclease (DNase 1), resulting in less enhancement of cAMP by VIP.
      CONCLUSIONS: In this study we failed to show VIP-responsive enhancement of cAMP
      in mucosal immune cells, suggesting that epithelial cells may be major effector
      cells of VIP in human colonic mucosa.

PMID- 10972179
TI  - Increased presence of eosinophilic granulocytes expressing transforming growth
      factor-beta1 in collagenous colitis.
AB  - BACKGROUND: Collagenous colitis is a disease characterized by chronic watery
      diarrhea, and on microscopic examination of colonic tissue, a typical thickening
      of the subepithelial collagen layer is seen. The etiology and pathophysiology
      behind this disease state are largely unknown. METHODS: We have used in situ
      hybridization and immunohistochemistry to study the expression of transforming
      growth factor (TGF) -beta1, a growth factor with the capacity to cause
      accumulation of collagen in tissues, in collagenous colitis. Colonic pinch biopsy
      specimens from a total of 34 patients were investigated: 17 patients with
      collagenous colitis and 17 controls. RESULTS: In patients with collagenous
      colitis there was increased expression of the TGF-beta1 gene compared with
      controls, as visualized by in situ hybridization. The vast majority of the TGF
      beta1-expressing cells were eosinophils, both in collagenous colitis and
      controls, but there were also scattered fibroblastic and histiocytic stromal
      cells. Immunohistochemistry showed the presence of TGF-beta1, mainly in
      eosinophils, in the colonic mucosa. Morphometric quantification showed 603 +/-
      192 eosinophils/mm2, (mean +/- standard error of the mean) in the colonic mucosa
      of patients with collagenous colitis compared with 30 +/- 7 eosinophils/mm2 in
      the controls. CONCLUSIONS: The present results suggest that eosinophils
      expressing TGF-beta1 may be of pathophysiologic importance in the connective
      tissue remodeling seen in collagenous colitis.

PMID- 10972180
TI  - Type I and III collagens in human colon cancer and diverticulosis.
AB  - BACKGROUND: Collagens are major proteins in the extracellular matrix, providing
      tissues with tensile strength. They are also important for cell adhesion and the
      invasion of malignant tumours. METHODS: Thirty-nine samples of human colon (24
      diverticulosis, 6 malignant tumours, 9 controls) were collected during elective
      surgery. Immunoassays for different domains of type I and III collagens and
      procollagens were used in soluble tissue extracts and trypsin digests of tissue
      samples. RESULTS: The contents of cross-linked type I and III collagen
      telopeptides and total collagen were similar in diverticulosis and healthy
      tissue, whereas in malignant tissue maturely cross-linked type III collagen was
      scarce. Furthermore, some of the cross-linked type I telopeptide antigens were
      exceptionally small in size, indicating that the cross-linking of type I collagen
      in collagen fibres is impaired in cancer. The rate of type I collagen synthesis
      was clearly increased in malignancy, but not significantly in diverticulosis.
      However, type III collagen synthesis was increased in diverticulosis, but not in
      malignancy. CONCLUSIONS: In colon malignancy, the collagen cross-linking process
      was aberrant and the synthesis of type I collagen increased. In diverticulosis,
      the synthesis of type III collagen was increased, suggesting only moderately
      increased metabolic activity.

PMID- 10972181
TI  - Epidermal growth factor and 17beta-estradiol effects on proliferation of a human
      gastric cancer cell line (AGS).
AB  - BACKGROUND: Recent evidence suggests that both estrogens and growth factors play
      an important role in the growth of gastrointestinal tumors. The expression of
      estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the
      gastrointestinal tract might therefore result in functional cross-talk between
      estrogens and EGF. The aim of the present study was to evaluate in vitro the
      effects of 17beta-estradiol and EGF administration on cell proliferation of a
      human gastric adenocarcinoma cell line (AGS) and investigate whether any
      interaction of these compounds may play a role in regulating gastric cancer cell
      proliferation. METHODS: Estrogen and EGFRs were detected by enzyme immunoassay.
      Cell proliferation was assessed with the MTT test. RESULTS: Exposure of AGS cells
      to increasing concentrations of 17beta-estradiol showed an anti-proliferative
      action at concentrations of 2 microM or higher. The addition of increasing
      concentrations of EGF stimulated cell growth, with a maximal response at 50 ng/ml
      EGF. The effect of increasing 17beta-estradiol concentrations combined with 50
      ng/ml EGF was to increase cell growth at the lower estradiol concentrations. At
      the highest estradiol concentration the EGF proliferative effect was suppressed,
      and a decrease in proliferation rates occurred. Moreover, a significant negative
      correlation was found between 17beta-estradiol concentrations and EGFR
      expression. CONCLUSIONS: These findings suggest that growth of cultured gastric
      cancer cells (AGS) might be modulated by sex steroid hormones through interaction
      with EGF.

PMID- 10972182
TI  - The significance of personality in pain from gallbladder stones.
AB  - BACKGROUND: The aim of the study was to investigate the association between
      personality factors related to coping styles and reported pain due to gallstones.
      METHODS: Personality trait measures were completed by 28 consecutive gallstone
      patients to provide estimates of positive coping resources (Life Regard Index,
      Sense of Coherence Scale, Sense of Humor Questionnaire) and negative coping
      resources (Eysenck Personality Questionnaire on Neuroticism, Tension, and Effort
      Stress Inventory). An overall index of gallstone-related complaints (pain) over
      the past 7 days/6 months was also obtained. Ultrasonography confirmed the
      gallstone condition. Multiple regression analyses tested the hypothesis that pain
      would be moderated by positive coping resources and mediated by negative coping
      resources. RESULTS: Reported pain was less severe with positive coping resources
      (39% of pain variance explained) and more severe with negative coping resources
      (45% of pain variance explained). CONCLUSION: The results confirm that mental
      coping resources have a significant role in pain differences among gallstone
      patients.

PMID- 10972183
TI  - The introduction and development of colonoscopy within a defined population in
      Sweden.
AB  - BACKGROUND: Our aim was to describe, in a population-based setting, the use of
      colonoscopy over time with special emphasis on indications, the competence of the
      endoscopists, and the frequency of total colonoscopies and to compare the number
      of colonoscopies with that of barium enemas. METHODS: All colonoscopy records
      during 1979-95 in a Swedish county (population, 258,000) were retrieved.
      Information was collected about the patients' demographics, the endoscopists,
      indications, findings, and type of colonoscopy. RESULTS: A total of 6066
      colonoscopies were performed in 4304 patients by 62 endoscopists. Of these, 562
      were not intended to be complete; of the other 5504 colonoscopies, 4153 were
      complete (75%). Of the patients 77% had undergone colonoscopy once, 14% twice,
      and 9% three times or more. Among the endoscopists 73% never performed more than
      50 colonoscopies, and 5% did more than 700 colonoscopies. Bleeding as an
      indication increased from 10% to 31%; polyps decreased from 30% to 10%, and
      unclear X-ray findings decreased from 28% to 4%. Diarrhoea and abdominal pain,
      both 0% in 1979, increased to 6% and 5%, respectively. Surveillance (cancer,
      polyps, colitis) was fairly stable, at 25%. Both the rate of complete
      colonoscopies and the proportion of colonoscopies done by experienced
      endoscopists increased with time. The annual number of barium enemas was
      relatively constant until 1992 but then decreased. CONCLUSIONS: The increased use
      of colonoscopy has resulted in a decrease in barium enemas. The competence of the
      endoscopists increased, resulting in a higher rate of complete colonoscopies.

PMID- 10972184
TI  - A simple method to establish short-term cultures of normal human colonic
      epithelial cells from endoscopic biopsy specimens. Comparison of isolation
      methods, assessment of viability and metabolic activity.
AB  - BACKGROUND: Abnormalities in colonic epithelial cell function have been
      implicated in the pathogenesis of various intestinal disorders, especially
      inflammatory bowel disease (IBD). The mechanisms, however, remain obscure owing
      to the lack of representative human colonic epithelial cell models. The aim of
      this study was to develop and validate a method for establishment of short-term
      culture of normal human colonic epithelial cells from endoscopic biopsies.
      METHODS: Epithelial cells were isolated from colonoscopic biopsies by means of
      ethylenediaminetetraacetic acid/ethylene glycol tetraacetic acid (EDTA/EGTA) (10
      or 60 min) or by enzyme treatment and cultured in collagen-coated wells.
      Viability was measured with a methyltetrazoleum conversion assay, confocal laser,
      and electron microscopy. Metabolic function was measured by means of butyrate
      oxidation, 14C-leucine and 3H-glucosamine incorporation; DNA synthesis by means
      of 3H-thymidine incorporation, and apoptosis with an enzyme-linked immunosorbent
      assay (ELISA) for histone-associated DNA fragments. Cell types were identified by
      immunocytochemistry. RESULTS: Ten minutes of EDTA/EGTA treatment released intact
      crypts and was superior to both the 60-min treatment and enzymatic treatment in
      terms of viability and nonepithelial cell contamination, respectively. Despite
      activation of detachment-induced apoptosis, a median 51% of the isolated cells
      was viable after 24 h of culture and metabolically active as judged by 3H
      thymidine, 14C-leucine, and 3H-glucosamine incorporation. Butyrate oxidation
      followed more complex kinetics (substrate activation) than observed previously in
      other models. The apparent Km values (medians) were 0.7 mM and 4.5 mM in low and
      high concentration ranges, respectively. CONCLUSION: We report a simple method to
      establish culture of human colonic epithelial cells from endoscopically obtained
      biopsy specimens, producing sufficient viable cells to perform metabolic studies
      pertinent to the pathogenesis of IBD and related human disorders.

PMID- 10972185
TI  - Gastric outlet obstruction by gallstone: Bouveret syndrome.
AB  - Gallstone has rarely been described as a cause of gastrointestinal obstruction.
      However, the relative incidence of gallstone ileus increases significantly with
      age. The gastric outlet is very seldom the location of obstruction by a
      gallstone. The diagnosis of this condition is not difficult. Nevertheless, if
      treatment is delayed, high morbidity and mortality rates result. Comprehensive
      treatment aims to relieve the obstruction, to close the biliodigestive fistula
      and to prevent further gallbladder complications. The surgeon who deals with this
      type of illness should tailor the treatment plan according to the age, general
      condition, and intraoperative findings of the individual patient. This paper
      presents a case report of an 88-year-old woman with gastric outlet obstruction
      caused by a gallstone.

PMID- 10972186
TI  - Concerning the original article of C. Weik and L. Greiner, 'The liver in
      hereditary hemorrhagic telangiectasia (Weber-Renduosler disease)'.

PMID- 10972187
TI  - Thermotoga maritima AglA, an extremely thermostable NAD+-, Mn2+-, and thiol
      dependent alpha-glucosidase.
AB  - The gene for the alpha-glucosidase AglA of the hyperthermophilic bacterium
      Thermotoga maritima MSB8, which was identified by phenotypic screening of a T.
      maritima gene library, is located within a cluster of genes involved in the
      hydrolysis of starch and maltodextrins and the uptake of maltooligosaccharides.
      According to its primary structure as deduced from the nucleotide sequence of the
      gene, AglA belongs to family 4 of glycosyl hydrolases. The enzyme was
      recombinantly expressed in Escherichia coli, purified, and characterized. The T.
      maritima alpha-glucosidase has the unusual property of requiring NAD+ and Mn2+
      for activity. Co2+ and Ni2+ also activated AglA, albeit less efficiently than
      Mn2+. T. maritima AglA represents the first example of a maltodextrin-degrading
      alpha-glucosidase with NAD+ and Mn2+ requirement. In addition, AglA activity
      depended on reducing conditions. This third requirement was met by the addition
      of dithiothreitol (DTT) or beta-mercaptoethanol to the assay. Using gel
      permeation chromatography, T. maritima AglA behaved as a dimer (two identical 55
      kDa subunits), irrespective of metal depletion or metal addition, and
      irrespective of the presence or absence of NAD+ or DTT. The enzyme hydrolyzes
      maltose and other small maltooligosaccharides but is inactive against the
      polymeric substrate starch. AglA is not specific with respect to the
      configuration at the C-4 position of its substrates because glycosidic
      derivatives of D-galactose are also hydrolyzed. In the presence of all cofactors,
      maximum activity was recorded at pH 7.5 and 90 degrees C (4-min assay). AglA is
      the most thermoactive and the most thermostable member of glycosyl hydrolase
      family 4. When incubated at 50 degrees C and 70 degrees C, the recombinant enzyme
      suffered partial inactivation during the first hours of incubation, but
      thereafter the residual activity did not drop below about 50% and 20% of the
      initial value, respectively, within a period of 48 h.

PMID- 10972188
TI  - Bacillus sp. WW3-SN6, a novel facultatively alkaliphilic bacterium isolated from
      the washwaters of edible olives.
AB  - A novel Gram-positive facultatively alkaliphilic, sporulating, rod-shaped
      bacterium, designated as WW3-SN6, has been isolated from the alkaline washwaters
      derived from the preparation of edible olives. The bacterium is nonmotile, and
      flagella are not observed. It is oxidase positive and catalase negative. The
      facultative alkaliphile grows from pH 7.0 to 10.5, with a broad optimum from pH
      8.0 to 9.0. It could grow in up to 15% (w/v) NaCl, and over the temperature range
      from 4 degrees to 37 degrees C, with an optimum between 27 degrees and 32 degrees
      C: therefore, it is both halotolerant and psychrotolerant. The bacterium is
      sensitive to a range of beta-lactam, sulfonamide, and aminoglycoside antibiotics,
      but resistant to trimethoprim. The range of amino acids, sugars, and polyols
      utilized as growth substrates indicates that this alkaliphile is a heterotrophic
      bacterium. D(+)-glucose, D(+)-glucose-6-phosphate, D(+)-cellobiose, starch, or
      sucrose are the substrates best utilized. The major membrane lipids are
      phosphatidylglycerol and diphosphatidylglycerol, with smaller amounts of
      phosphatidylethanolamine and an unknown phospholipid. During growth at high pH,
      the proportion of phosphatidylglycerol is increased relative to
      phosphatidylethanolamine. The fatty acyl components in the membrane phospholipids
      are mainly branched chain, with 13-methyl tetradecanoic and 12-methyl
      tetradecanoic acids as the predominant components. The G + C content of the
      genomic DNA is 41.1 +/- 1.0 mol%. The results of 16S ribosomal RNA sequence
      analysis place this alkaliphilic bacterium in a cluster, together with an unnamed
      alkaliphilic Bacillus species (98.2% similarity).

PMID- 10972189
TI  - Characterization and comparative study of the rrn operons of alkaliphilic
      Bacillus halodurans C-125.
AB  - The ribosomal RNA operons (rrn) of alkaliphilic Bacillus halodurans C-125 were
      characterized and compared with those of B. subtilis. We isolated clones
      containing rrn operons from a lambda phage library of the C-125 chromosome, and
      the complete nucleotide sequence of each was determined. Eight rrn operons were
      identified by PFGE analysis of the C-125 chromosome digested with I-CeuI. The
      transcriptional orientation of the rrn operons mapped on the chromosome by
      Southern hybridization analysis was the same as the direction of replication of
      the chromosome. These operons were designated as rrnA-H, starting from the oriC
      locus in clockwise rotation. Sequence and structural analyses of these operons
      suggested that six of the rrn operons in the C-125 chromosome, rrnA, rrnB, rrnC
      rrnD, rrnE, and rrnH, correspond to rrnO, rrnA, rrnJ-rrnW, rrnI, and rrnD in B.
      subtilis, whereas the other rrn operons (rrnF and rrnG) were specifically
      observed in C-125. The rrn loci were positioned from 0 degrees to 90 degrees on
      the physical map, with the oriC locus assigned the position zero degrees. Two
      ORFs annotated as tnpA and ykfC, whose gene products are likely to act as
      transposases, were found downstream of these six operons. Comparative analysis of
      the 16S-23S and 23S-5S ITS (internally transcribed sequence) regions of B.
      halodurans C-125 and those of B. subtilis revealed that the ITS regions in C-125
      were much longer than those in B. subtilis. There was no substantial difference
      in the length of potential promoter sequences in B. halodurans and B. subtilis.

PMID- 10972190
TI  - Cloning, expression, and characterization of DNA polymerase I from the
      hyperthermophilic archaea Thermococcus fumicolans.
AB  - The DNA polymerase I gene of a newly described deep-sea hydrothermal vent Archaea
      species, Thermococcus fumicolans, from IFREMERS's collection of hyperthermophiles
      has been cloned in Escherichia coli. As in Thermococcus litoralis, the gene is
      split by two intervening sequences (IVS) encoding inteins inserted in sites A and
      C of family B DNA polymerases. The entire DNA polymerase gene, containing both
      inteins, was expressed at 30 degrees C in E. coli strain BL21(DE3)pLysS using the
      pARHS2 expression vector. The native polypeptide precursor of 170kDa was
      obtained, and intein splicing as well as ligation of the three exteins was
      observed in vitro after heat exposure. The recombinant enzyme was purified and
      some of its activities were characterized: polymerization, thermostability,
      exonuclease activities, and fidelity.

PMID- 10972191
TI  - Thermolabile xylanase of the Antarctic yeast Cryptococcus adeliae: production and
      properties.
AB  - Xylanase production by the Antarctic psychrophilic yeast Cryptococcus adeliae was
      increased 4.3 fold by optimizing the culture medium composition using statistical
      designs. The optimized medium containing 24.2 g l(-1) xylan and 10.2 g l(-1)
      yeast extract and having an initial pH of 7.5 yielded xylanase activity at 400
      nkat (nanokatal) ml(-1) after 168-h shake culture at 4 degrees C. In addition,
      very little endoglucanase, beta-mannanase, beta-xylosidase, beta-glucosidase,
      alpha-L-arabinofuranosidase, and no filter paper cellulase activities were
      detected. Among 12 carbon sources tested, maximum xylanase activity was induced
      by xylan, followed by lignocelluloses such as steamed wheat straw and alkali
      treated bagasse. The level of enzyme activity produced on other carbon sources
      appeared to be constitutive. Among the complex organic nitrogen sources tested,
      the xylanase activity was most enhanced by yeast extract, followed by soymeal,
      Pharmamedia (cotton seed protein), and Alburex (potato protein). A batch culture
      at 10 degrees C in a 5-1 fermenter (3.5-1 working volume) using the optimized
      medium gave 385 nkat at 111 h of cultivation. The crude xylanase showed optimal
      activity at pH 5.0-5.5 and good stability at pH 4-9 (21 h at 4 degrees C).
      Although the enzyme was maximally active at 45 degrees - 50 degrees C, it
      appeared very thermolabile, showing a half-life of 78 min at 35 degrees C. At 40
      degrees - 50 degrees C, it lost 71%-95% activity within 5 min. This is the first
      report on the production as well as on the properties of thermolabile xylanase
      produced by an Antarctic yeast.

PMID- 10972192
TI  - A new facultatively autotrophic hydrogen- and sulfur-oxidizing bacterium from an
      alkaline environment.
AB  - An alkaliphilic bacterium, strain AHO 1, was isolated from an enrichment culture
      with hydrogen at pH 10 inoculated with a composite sample of sediments from five
      highly alkaline soda lakes (Kenya). This bacterium is a gram-negative, nonmotile,
      rod-shaped, obligately aerobic, and facultatively autotrophic hydrogen-oxidizing
      organism. It was able to oxidize reduced sulfur compounds to sulfate during
      heterotrophic growth. It utilized a wide range of organic compounds as carbon and
      energy sources and grew mixotrophically with hydrogen and acetate. With sulfur
      compounds, mixotrophic growth was observed only in acetate-limited continuous
      culture. The normal pH range for autotrophic growth with hydrogen was pH 8.0
      10.25, with a pH optimum at 9-9.5. Growth at pH values lower than 8.0 was
      extremely slow. Heterotrophic growth with acetate was optimal at pH 10.0. The
      hydrogen-oxidizing activity of whole cells was maximal at pH 9.0 and still
      substantial up to pH 11. NAD-dependent hydrogenase activity was found in the
      soluble fraction of the cell-free extract, but no methylene blue-dependent
      activity in either the soluble or membrane fractions was observed. On the basis
      of its pH profile, the soluble hydrogenase of strain AHO 1 was a typical pH
      neutral enzyme. Phylogenetic analysis revealed that strain AHO 1 belongs to the
      alpha-3 subgroup of the Proteobacteria with a closest relation to a recently
      described alkaliphilic aerobic bacteriochlorophyll a-containing bacterium
      "Roseinatronobacter thiooxidans."

PMID- 10972193
TI  - A simplified method for the cultivation of extreme anaerobic Archaea based on the
      use of sodium sulfite as reducing agent.
AB  - The extreme sensitivity of many Archaea to oxygen is a major obstacle for their
      cultivation in the laboratory and the development of archaeal genetic exchange
      systems. The technique of Balch and Wolfe (1976) is suitable for the cultivation
      of anaerobic Archaea but involves time-consuming procedures such as the use of
      air locks and glove boxes. We describe here a procedure for the cultivation of
      anaerobic Archaea that is more convenient and faster and allows the preparation
      of liquid media without the use of an anaerobic chamber. When the reducing agent
      sodium sulfide (Na2S) was replaced by sodium sulfite (Na2SO3), anaerobic media
      could be prepared without protection from oxygen outside an anaerobic chamber.
      Exchange of the headspace of serum bottles by appropriate gases was sufficient to
      maintain anaerobic conditions in the culture media. Organisms that were unable to
      utilize sulfite as a source for cellular sulfur were supplemented with hydrogen
      sulfide. H2S was simply added to the headspace of serum bottles by a syringe. The
      use of H2S as a source for sulfur minimized the precipitation of cations by
      sulfide. Representatives of 12 genera of anaerobic Archaea studied here were able
      to grow in media prepared by this procedure. For the extremely oxygen-sensitive
      organism Methanococcus thermolithotrophicus, we show that plates could be
      prepared outside an anaerobic chamber when sulfite was used as reducing agent.
      The application of this method may faciliate the cultivation and handling of
      extreme anaerobic Archaea considerably.

PMID- 10972194
TI  - Effect of Jindangwon on streptozotocin-induced diabetes.
AB  - The inhibitory effects of the traditional herbal medicine Jindangwon (JDW) on
      streptozotocin (ST)-induced diabetic mellitus were studied using the ST-treated
      diabetic model. Glucokinase activity of pancreatic islets was severely impaired
      by ST treatment. However, when ST-treated islets were treated with 1 mg/ml of
      JDW, the enzyme activities of glucokinase and hexokinase were protected, glucose
      6-phosphatase was not. When the effects of JDW on ST-induced ATP/ADP ratio of
      islets were assayed, JDW was effective in restoring of ATP/ADP ratio. In
      addition, ST decreased the enzyme activities of PDH, while JDW had a protective
      effect on the enzyme. ST-induced cGMP accumulation was significantly inhibited by
      JDW treatment. Furthermore, ST-induced nitrite formation was significantly
      inhibited by JDW treatment. JDW also showed the suppressed nitrite production in
      ST-treated pancreatic islet cells. When the islets (200/condition) were treated
      with ST (5 mM for 30 min), and then JDW was added to the ST-treated cells, 1.0
      mg/ml of JDW showed the activated and recovered aconitase activity in pancreatic
      islet cells. When the effect of ST on the gene expression of pancreatic GLUT2 and
      glucokinase were examined, the level of GLUT2 and glucokinase mRNA in pancreatic
      islets was significantly decreased. However, JDW protected and improved the
      expression of protein and genes, indicating that JDW is effective on ST-induced
      inhibition of gene expression of GLUT2, glucokinase and proinsulin in islets.
      These results suggested that JDW is effective in this model to treat ST-induced
      diabetes.

PMID- 10972195
TI  - Modulation of medical prefrontal cortical D1 receptors on the excitatory firing
      activity of nucleus accumbens neurons elicited by (-)-Stepholidine.
AB  - (-)-Stepholidine (SPD), with D1 agonistic action, elicited an excitatory firing
      activity of nucleus accumbens (NAc) neurons by intravenous administration, but
      this effect was hardly observed by iontophoresis of SPD into the NAc. The present
      study intends to determine whether D1 receptors in the medial prefrontal cortex
      (mPFC) are involved in the action of SPD on the firing activity of NAc neurons in
      the chloral hydrate-anesthetized male rats. The results showed that the intra
      mPFC microinjected SCH-23390 (D1 antagonist, 30 mM), but not the D2 antagonist
      spiperone (30 mM), significantly attenuated the enhanced firing activity induced
      by intravenous injection of SPD (2 mg/kg). Similarly, the excitatory firing of
      NAc neurons was also exhibited by the microinjection of either SPD or D1 agonist
      SKF-38393 into the mPFC. The SPD-induced excitatory effect was in a dose
      dependent way from 277.8 +/- 51.3% (10 mM) to 1105.4 +/- 283.5% (30 mM) of NAc
      basal firing, which was completely reversed by SCH-23390 (i.v.). Furthermore, the
      direct D1 agonistic action of SPD on the mPFC neuron was observed with
      microiontophoresis. These results indicate that SPD possesses a direct agonistic
      action on the mPFC D1 receptors, by which it modulates the firing activity of NAc
      neurons.

PMID- 10972196
TI  - Epinephrine stimulates the Na+-K+ ATPase in isolated rat jejunal crypt cells.
AB  - The effect of epinephrine on the activity of the Na+-K+ ATPase was studied in
      isolated rat jejunal cells. The activity of the pump was assessed by measuring
      the ouabain inhibitable K+ accumulation by the enterocytes using 86Rb as a
      tracer. Epinephrine stimulated significantly the Na+-K+ ATPase in crypt cells but
      not in villus cells. This effect was still apparent in presence of propranolol
      and prazocin but disappeared in presence of yohimbine. Amiloride did not affect
      the epinephrine-induced stimulation. Calcium channel blockers and dibutyryl cAMP
      enhanced the activity of the pump, and exerted respectively overlapping and
      additive effects with epinephrine, when added simultaneously. The calcium
      ionophore A23187 inhibited the basal activity of the ATPase and the stimulatory
      effect of epinephrine disappeared in its presence. These results suggest that
      epinephrine stimulates the Na+-K+ ATPase in jejunal crypt cells by activating
      alpha2 receptors and decreasing intracellular calcium, and not by altering cAMP
      levels.

PMID- 10972197
TI  - Astrocyte beta1-adrenergic receptor immunoreactivity and agonist induced
      increases in [Ca2+]i: differential results indicative of a modified membrane
      receptor.
AB  - Antibodies against the C-terminus of the beta1-adrenergic receptor were used for
      staining cultured astrocytes from the rat cerebral cortex. Immunoreactivity was
      found to be localized exclusively to an intracellular organelle structure similar
      to the Golgi complex, with no staining of the plasma membrane. The astrocytes
      stained positive with BODIPY CGP 12177, a FITC-conjugated beta-adrenergic
      receptor agonist, and this staining was blocked by the beta1-adrenergic
      antagonist atenolol, indicating that these receptors are expressed on the surface
      of the astrocytes. The presence of functional plasma membrane beta1-adrenergic
      receptors was further verified using microspectrofluorometry for measurements of
      intracellular calcium changes upon beta-adrenergic agonist stimulation.
      Intracellular immunoreactivity confined to the organelles was also found in
      astrocytes from mixed astroglial-neuronal cultures. In contrast, the neurons in
      these cultures showed a strong labeling of the cell bodies by the beta1
      adrenergic receptor antibodies. Thus, the beta1-adrenergic receptor antibody,
      which stains the cell bodies of the neurons, recognizes the astroglial receptors
      only intracellularly, although functional beta1-adrenergic receptors are present
      on the astroglial surface. Taken together, these data suggest that the beta1
      adrenergic receptors observed intracellularly might be processed on their passage
      to the surface to a modified form of the final plasma membrane receptor, which is
      not recognized by the antibodies.

PMID- 10972198
TI  - Anti-proliferative effect of ginseng saponins on human prostate cancer cell line.
AB  - Ginseng is a medicinal herb widely used in Asian countries, and many of its
      pharmacological actions are attributed to the ginsenosides. In a study of the
      anti-proliferative activity of ginsenosides using human prostate carcinoma LNCaP
      cell line, ginsenoside Rg3 displayed growth inhibitory activity. The cells lost
      its adherent property after incubation in the presence of 250 microM of
      ginsenoside for 48h. The expression of biomarker genes, including prostate
      specific antigen (PSA), androgen receptor (AR) and 5alpha-reductase (5alphaR),
      and that of the proliferating cell nuclear antigen (PCNA), were suppressed.
      Ginsenoside Rg3 induced classic apoptotic morphology and interfered with the
      expression of apoptosis-related genes, bcl-2 and caspase-3, in LNCaP cells, as
      demonstrated by fluorescence microscopy, flow cytometry and reverse transcriptase
      polymerase chain reaction. Taken our results together, we suggested that
      ginsenoside Rg3 activated the expression of cyclin-kinase inhibitors, p21 and
      p27, arrested LNCaP cells at G1 phase, and subsequently inhibited cell growth
      through a caspase3-mediated apoptosis mechanism.

PMID- 10972199
TI  - Dietary lipids affect human ethanol-inducible CYP2E1 gene expression in vivo in
      mononuclear cells.
AB  - We tested the hypothesis that dietary cholesterol modulate human ethanol
      inducible CYP2E1 expression in vivo in circulating mononuclear cells. Healthy
      volunteers (n= 10) were submitted to a low fat low cholesterol diet for 4 days
      (day 0-day 3, LFLC). Cholesterol (595 +/- 56 mg/day) was then reintroduced for 7
      days (day 4-day 10, LFHC). In the same time, controls subjects (n=7) did not
      change their habitual daily diet. CYP2E1 mRNA levels, evaluated in mononuclear
      cells, decreased in experimental subjects during both LFLC and LFHC from 100% to
      53 +/- 5%, (p<0.001) with a main decrease during LFLC period (100% to 71 +/- 16%,
      p=0.05). Immunoreactive CYP2E1 showed a similar pattern and decreased from 100 to
      62 +/- 12% during the trial (p<0.05). No significant change occured in control
      subjects. Between day 0 and day 11, changes in CYP2E1 mRNA correlated positively
      with plasma cholesterol (r2=0.67, p<0.001) and HDL cholesterol concentrations
      (r2=0.61, p<0.001). In contrast, no correlation was found between plasma fatty
      acids concentrations and CYP2E1 expression. The present results suggest that
      lipid factors regulate CYP2E1 expression, in vivo, in human mononuclear cells. In
      particular, plasma cholesterol concentrations may play an important role in this
      regulation.

PMID- 10972200
TI  - Changes in the intracellular homocysteine and glutathione content associated with
      aging.
AB  - Since moderate hyperhomocysteinemia is an independent risk factor for vascular
      disease by mean of its oxidant effect and glutathione plays a main role as
      intracellular redox-regulating agent, we have studied for the first time the
      total intracellular content of homocysteine in aging. Plasma homocysteine
      concentration, total intracellular and plasma glutathione, and other related
      thiol compounds such as cysteine and the glutathione catabolite cysteinglycine
      were also studied. Forty three healthy elderly subjects and twenty seven healthy
      young ones were studied. The total intracellular peripheral blood mononuclear
      cell content was higher for homocysteine, cysteine and cysteinglycine, whereas
      that of the total glutathione was greatly decreased in elderly people with
      respect to young ones. Elderly subjects showed significantly higher levels than
      young ones of total plasma homocysteine and cysteinglycine, but not cysteine,
      whereas total plasma glutathione levels were increased. In addition, elderly
      subjects showed significantly decreased plasma vitamin E levels and increased
      concentrations of serum lipid peroxides measured as TBARS (reaction product of
      malondialdehyde with thiobarbituric acid). The intracellular glutathione content
      presented significantly negative correlation with serum TBARS, and intracellular
      and plasma homocysteine levels. These findings show an increase of homocysteine
      synthesis associated with aging, which in turn can produce an augmented oxidant
      effect on endothelium, and an impaired intracellular antioxidant capacity leading
      to an enhanced lipid peroxidation and decreased total intracellular glutathione
      content.

PMID- 10972201
TI  - Acute effects of aspartame on aggression and neurochemistry of rats.
AB  - The inverse relationship between serotonin and aggression was investigated in
      rats treated with aspartame, a sweetener thought to interfere with the synthesis
      of this neurotransmitter. Eleven adult, male Long-Evans rats received either
      aspartame (200-800 mg/kg, IP) or the vehicle prior to testing in a standard
      resident-intruder paradigm. Contrary to our hypothesis, aspartame significantly
      decreased aggression as shown by increased latencies to the first attack and
      decreased number of bites per session. Corresponding with the effects on
      aggression, aspartame significantly increased striatal levels of serotonin. It
      was concluded that high doses of aspartame reduced aggressive attack via a
      serotonergic mechanism while the lower dose was without effect on either
      variable.

PMID- 10972202
TI  - Growth-altering effects of sodium hypochlorite in cultured human dermal
      fibroblasts.
AB  - Sodium hypochlorite, the most widely used antimicrobial active chlorine compound
      in chemical disinfection, is little used as an antiseptic in clinical practice.
      This study aimed to assess the capacity of hypochlorite to alter human dermal
      fibroblast growth in vitro in relation to the concentration and exposure time.
      Effects of decreasing concentrations of hypochlorite (0.5%-0.00025%) on
      fibroblast adherence capacity and proliferation, according to varying exposure
      times and fetal calf serum (FCS) concentrations were investigated combining XTT
      assay, which provides cytochemical quantification of metabolically-active cell
      number, and total cell protein content, an indirect method for assessing
      substrate-adhered cell number. Initial cytotoxicity was produced at 0.0075%
      hypochlorite within contact time of two hours, provoking concentration-dependent
      cell detachment. From 0.1% upwards, NaOCl exerted a profound cytotoxic effect on
      fibroblasts. At later stages (4 h) and concentrations > or = 0.01% hypochlorite
      produced dose-dependent mitochondrial dysfunction: cell survival progressively
      diminished from 71% to 10%. Cytotoxic effects were not significantly affected by
      exposure-time periods, probably because maximum chlorine is released within the
      first four hours. Hypochlorite concentrations from 0.005% to 0.00025% were found
      to have no inhibitory effects on cell growth; in fact, they appear to exhibit the
      opposite effect. Increments in protein content found after 24 h exposure ranged
      from 30% to 120% above control values. Hypochlorite is highly cytotoxic for
      fibroblasts at concentrations > or = 0.01% provoking concentration-dependent loss
      of cell adherence capacity and mitochondrial dysfunction. In contrast, a
      mitogenic effect was observed with concentrations < or = 0.005% which supports
      NaOCl as a source growth-promoting activity in cultured human fibroblasts.
      Hypochlorite proved to be a highly reactive molecule which inhibits or stimulates
      cell division according to the concentration.

PMID- 10972203
TI  - Modulation of halofantrine resistance after coadministration of halofantrine with
      diverse pharmacological agents in a rodent malaria model.
AB  - The declining efficacy of antimalarial drugs against Plasmodium falciparum
      strains has been reported from several endemic regions of the world. Strategic
      evaluation of several pharmacological agents in combination with chloroquine to
      enhance the sensitivity of the latter against resistant parasites has been
      documented in several studies. However no attempts have been directed to monitor
      the efficacy of such biological response modifiers for reversing the resistance
      to halofantrine. In the present study the comparative efficacy of a total of 22
      pharmacological agents representing diverse categories including antihistamines,
      antidepressants, calcium channel blockers, neuroleptics etc. has been determined
      in combination with halofantrine against halofantrine resistant Plasmodium yoelii
      nigeriensis. Results show significant potentiation of the efficacy of
      halofantrine when administered concurrently with histamine H1 receptor
      antagonists cyproheptadine and ketotifen. Combination with pheniramine,
      amitriptyline, verapamil and penfluridol also produced moderate degree of
      potentiation which was well marked during the early phase of progression of
      parasitaemia.

PMID- 10972204
TI  - Evidence of histamine receptor function in isolated horse penile dorsal arteries.
AB  - The effect of histamine (10(-9)-10(-3) M) on horse penile dorsal artery was
      evaluated. Precontracted vessels showed a biphasic response (relaxation
      contraction) to histamine, while at basal tone, histamine only induced a
      contractile effect. The H1 receptor agonist, 2-pyridylethylamine (PEA) (10(-9)
      10(-3) M), induced concentration-dependent relaxation in precontracted rings and
      provoked vasoconstriction at basal tone. Mepyramine (10(-9)-10(8) M), an H1
      receptor antagonist, competitively antagonized the relaxant response to histamine
      (pA2 = 9.7) and PEA (pA2 = 9.2). At basal tone, mepyramine (10(-10)-10(-8) M)
      also caused a rightward shift in the histamine contraction curve (pA2 = 10.1).
      Mepyramine (10(-9)-10(-8) M)/PEA Schild plots for resting vessels yielded a pA2
      value of 9.4. A regulatory role for H2 and H3 receptors was precluded since there
      was no response to their agonists (dimaprit (10(-9)-10(-3) M), (R)-alpha
      methylhistamine (10(-10)- 3 x 10(-4) M)), and antagonists (cimetidine (10(-5) M),
      thioperamide (10(-6) M)) did not affect control curves. Removal of the
      endothelium abolished the relaxant component causing a leftward shift in the
      contractile component in precontracted rings, with no effect on maximum
      contraction. Inhibitors of nitric oxide (NO) synthesis, L-NAME (3 x 10(-4) M) and
      L-NOARG (3 x 10(-4) M), modified the relaxant response while contraction was
      unaffected. L-Arginine (3 x 10(-4) M) potentiated maximum relaxation but did not
      affect contraction in precontracted rings. Effects of a prostanoid and K+
      channels were ruled out. The biphasic response of precontracted vessels persisted
      in the presence of indomethacin (3 x 10(-6) M), tetraethylammonium (10(-3) M) and
      gliblenclamide (10(-5) M). L-NAME plus indomethacin, or this combination plus TEA
      or glibenclamide produced similar effects as isolated treatments. In resting
      vessels, histamine contraction was also unaffected by the lack of endothelium, or
      L-NAME, L-arginine or indomethacin pretreatment. The biphasic response to
      histamine is probably mediated by H1 receptors with a partial role for NO in the
      relaxant response in precontracted vessels. In the absence of tone, the
      contractile effect may be mediated by direct action on smooth muscle.

PMID- 10972205
TI  - Vanadate-evoked relaxation of the perfused rat mesenteric vascular bed.
AB  - Sodium orthovanadate (SOV) can contract smooth muscle; however, little is known
      about its effect on the vascular endothelium. We compared the vasorelaxant
      effects of acetylcholine (ACh) and SOV in the preconstricted, isolated perfused
      mesenteric vascular bed (MVB) of Sprague-Dawley rats. The maximal relaxation
      response evoked by SOV (40-45%) was lower than ACh (92-94%) but the IC50 values
      were similar. At concentrations > 1 mM, SOV elevated the basal tone. Endothelial
      denudation resulted in a substantial reduction of relaxation responses to both
      agents, whereas either nitric oxide synthase (NOS) inhibitors or high KCl
      partially reduced the responses. A combination of NOS inhibitors along with
      either a calcium-activated potassium channel (KCa) blocker, tetrabutylammonium
      (TBA), or high KCI inhibited the responses to a similar extent as endothelium
      denudation. Neither clotrimazole nor TBA attenuated ACh responses; however,
      maximal responses to SOV in the presence of TBA or clotrimazole were reduced.
      Indomethacin had no effect on responses to either agonists. These results
      indicate that like ACh, SOV-mediated vasorelaxation of the MVB involves
      recruitment of both endothelial derived hyperpolarizing factor (EDHF) and
      endothelial derived nitric oxide (NO) and not vasodilator eicosanoids. As the
      relaxation to SOV was dose-dependent at a low concentration range, it is likely
      that vanadate is involved in the regulation of total peripheral resistance.

PMID- 10972206
TI  - The effects of herbal oxytocics on the isolated "stripped" myometrium model.
AB  - Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents
      in South African traditional herbal medicine. Aqueous extracts of A. africanus
      and C. miniata leaves have been shown to possess similar uterotonic activities in
      the isolated whole uterus preparation. The uterus however, comprises a myometrial
      and an endometrial layer and the activity of both oxytocin and the prostaglandins
      differs in these layers. The aim of this study was to determine the uterotonic
      activity of the herbal remedies in an endometrium-free preparation (i.e.
      "stripped" myometrium) and, if active, whether this effect could be related to
      prostaglandin synthesis or to interaction with specific receptors. The effects of
      the herbal extracts were tested on the isolated "stripped" rat myometrium
      preparation. Both herbal extracts caused a direct contractile response by the
      isolated tissue. Pretreatment of the myometrium with either plant extract
      augmented the initial response to acetylcholine. Preincubation with atropine
      inhibited the response to cumulative dosage of Agapanthus extract but had no
      effect on the response to Clivia. Indomethacin administration did not affect the
      response of the myometrium to cumulative dosage of acetylcholine, oxytocin or
      Clivia extract but inhibited the response to Agapanthus extract. These results
      clearly indicate that the Agapanthus and Clivia herbal extracts exhibited
      uterotonic activity in this model. The study illustrates that the "stripped"
      myometrium model has successfully differentiated between the mechanisms of action
      of two herbal oxytocics compared to the whole uterus preparation where their
      uterotonic activity was thought to be similar.

PMID- 10972207
TI  - Assessment of graft function before liver transplantation: quest for the lost
      ark?

PMID- 10972208
TI  - Inducing unresponsiveness in allopeptide specific T cells: are altered peptide
      ligands the answer?

PMID- 10972209
TI  - Are pigs transgenic for human complement regulatory proteins necessary for
      xenotransplantation?

PMID- 10972210
TI  - Comment on "Ontogeny of antipig xenoantibody and hyperacute rejection".

PMID- 10972211
TI  - Long-term changes in left ventricular hypertrophy after renal transplantation.
AB  - BACKGROUND: Concentric and eccentric left ventricular hypertrophy are common
      progressive disorders in dialysis patients and are associated with cardiac
      failure and death. Although partial regression of these abnormalities is known to
      occur during the first post-transplant year, their long-term evolution is
      unknown. METHODS: A total of 143 of 433 dialysis patients participating in a long
      term prospective cohort study received renal transplants. Laboratory parameters
      were assessed monthly. Echocardiography was performed annually. Left ventricular
      mass index (LVMI) and cavity volume index were calculated according to standard
      formulae. Multiple linear regression was used to model change in LVMI as a
      function of baseline clinical and laboratory variables. RESULTS: LVMI fell from
      161 g/m2 at 1 year to 146 g/m2 (P=0.009) g/m2 after 2 years. No further
      regression was seen in years 3 and 4. Left ventricular volume index showed
      similar trends, with a decline from year 1 to year 2 (P=0.05) followed by
      stabilization in years 3 and 4. Older age, long duration of hypertension, need
      for more than one antihypertensive, high pulse pressure in normal-size hearts,
      and low pulse pressure in dilated hearts were significantly associated with
      failure of regression of LVMI between the first and second years (MLR,
      P<0.000001, r2=0.57). CONCLUSIONS: Regression of left ventricular hypertrophy
      continues beyond the first year after renal transplantation, reaching a nadir at
      2 years and persisting into the third and fourth posttransplant years. Failure to
      regress was associated with older age, hypertension, high pulse pressure in
      normal-size hearts and low pulse pressure in dilated hearts.

PMID- 10972212
TI  - Opening of mitochondrial potassium channels: a new target for graft preservation
      strategies?
AB  - BACKGROUND: This study was designed to assess the protective effects of the
      mitochondrial adenosine triphosphate-sensitive potassium channel (KATP) opener
      diazoxide as an additive to heart preservation solution. METHODS: Forty isolated
      isovolumic buffer-perfused rat hearts were divided into four groups. Groups I and
      III hearts were arrested with and cold-stored in Celsior solution for 4 hr and 10
      hr, respectively. In Groups II and IV, hearts underwent a protocol similar to
      that used in Group I and III, respectively, except that Celsior was supplemented
      with 100 micromol/L of diazoxide. RESULTS: The protective effects of diazoxide
      were primarily manifest as a better preservation of diastolic function and a
      reduction of myocardial edema. The improvement of postischemic systolic function
      was observed only after prolonged exposure to diazoxide in Group IV, compared
      with Group III. The endothelium-dependent and endothelium-independent coronary
      flow postischemic responses were not affected by the supplementation of Celsior
      with diazoxide. CONCLUSIONS: Pharmacologic activation of mitochondrial KATP
      channels seems to be an effective means of improving preservation of cold-stored
      hearts, which is consistent with the presumed role of these channels as end
      effectors of the cardioprotective preconditioning pathway.

PMID- 10972214
TI  - Matrix accumulation in mesangial cells exposed to cyclosporine A requires a
      permissive genetic background.
AB  - BACKGROUND: Chronic nephrotoxicity is an important adverse effect of cyclosporine
      A (CsA) therapy. Tubulo-interstitial lesions and arteriolopathy are common
      histologic findings. Glomerular lesions are also described, but they are of
      variable severity. The aim of our study is to determine whether CsA has a direct
      effect on mesangial cells and whether the cellular response depends on the
      genetic background. METHODS: We studied mesangial cells isolated from mice
      susceptible (ROP/Le-+Es1(b)+Es1(a), ROP) and resistant to glomerulosclerosis
      (B6SJLF1, C57). We previously showed that sclerosis-prone and sclerosis-resistant
      phenotypes are maintained in vitro. We examined whether CsA exposure directly
      affected extracellular matrix turnover in mesangial cells and whether the
      response is determined by the genetic background. Extracellular matrix synthesis
      and degradation were studied by proline incorporation, ELISA, reverse
      transcription-polymerase chain reaction, zymography, and reverse zymography. We
      chose a CsA dose that induced neither cytotoxicity nor apoptosis (1 microg/ml).
      RESULTS: At the dose of 1 microg/ml total collagen accumulation was increased in
      ROP but not in C57 cells. Matrix metalloproteinase (MMP)-2 activity and mRNA
      levels were selectively decreased in ROP cells. CsA exposure did not affect
      tissue inhibitors of MMP (TIMP)-1 and -2 activity or TGF-beta1 mRNA expression
      and protein synthesis in either cell line. CONCLUSION: CsA increases total
      collagen accumulation in mesangial cells from sclerosis-prone mice by decreasing
      MMP-2 activity, but does not affect cells from sclerosis-resistant mice. Thus,
      CsA directly affects mesangial cells, but only those with a permissive genetic
      background for glomerulosclerosis.

PMID- 10972213
TI  - Cloning of porcine intercellular adhesion molecule-1 and characterization of its
      induction on endothelial cells by cytokines.
AB  - BACKGROUND: The transplantation of pig organs into humans requires a detailed
      knowledge of similarities and differences between the two species in the
      molecular physiology of host defense mechanisms. We therefore set out to identify
      porcine intercellular adhesion molecule (ICAM)-1 and to characterize its
      expression by endothelial cells. METHODS: Porcine ICAM-1 cDNA was isolated from
      an endothelial cell cDNA library. An anti-pig ICAM-1 monoclonal antibody was
      generated and used to investigate the regulation by cytokines of ICAM-1
      expression by porcine aortic endothelial cells (PAEC), using flow cytometry.
      RESULTS: We found that porcine ICAM-1 was similar in primary structure to human
      ICAM-1, with five Ig-like domains. COS-7 cells transfected with porcine ICAM-1
      supported beta2 but not alpha4 integrin-dependent adhesion of human T
      lymphoblasts. There was a low-level surface expression of ICAM-1 on unstimulated
      PAEC and increased expression after stimulation with tumor necrosis factor (TNF)
      alpha. However expression of ICAM-1 seemed to be significantly lower than that of
      vascular cell adhesion molecule-1, both on unstimulated and TNF-alpha-activated
      PAEC. Recombinant porcine interferon-gamma weakly stimulated ICAM-1 expression
      when incubated alone with PAEC but had an inhibitory effect on the increase in
      ICAM-1 due to TNF-alpha, both at 8 and 24 hr. CONCLUSIONS: Our observations
      confirm the existence of ICAM-1 in the pig and provide novel insights into how
      porcine and human endothelial cells differ in terms of adhesion molecule
      expression and cytokine responsiveness. Such differences are potentially
      important in interpreting models of inflammation in the pig and also in
      understanding the process of rejection of porcine xenografts.

PMID- 10972215
TI  - Predictive negative value of persistent low Epstein-Barr virus viral load after
      intestinal transplantation in children.
AB  - BACKGROUND: The correlation between an elevated Epstein-Barr virus (EBV) viral
      load in the peripheral blood and the subsequent development of EBV-associated
      posttransplant lymphoproliferative disease (PTLD) is the basis for strategies
      using serial measurements of the EBV viral load to guide preemptive therapy (PT).
      Neither the frequency, duration of monitoring, nor the predictive negative value
      of viral load monitoring for asymptomatic patients with persistent low or
      nondetectable viral loads against the development of PTLD has been established.
      METHODS: Since April 1994, children undergoing intestinal transplantation (ITx)
      underwent serial monitoring of the EBV viral load in their peripheral blood using
      a quantitative competitive EBV polymerase chain reaction assay (PCR). Samples
      were obtained every 2 weeks for the first 3 months and then every 1-3 months
      depending on the patients clinical condition. EBV viral loads > or =40 (for
      patients who were EBV seronegative pre-ITx) and > or =200 (for those who were
      seropositive) genome copies/10(5) peripheral blood lymphocytes were felt to
      identify patients at increased risk for PTLD and generally prompted PT. RESULTS:
      A total of 30 ITx recipients were compliant with our monitoring protocol; 23/30
      are alive 6-59 months post-ITx. A total of 12/30 never had a viral load >40 and
      did not receive PT. In contrast, 18/30 had > or =1 high viral load (> or =200);
      the first high viral load was measured a median of 59 days post-ITx (range 1
      440). A late rise (>6 months post-ITx) was seen in only 2/18 children. A total of
      0/12 patients with persistently low viral loads received PT and none developed
      PTLD. In contrast, 5/18 with > or =1 one high viral load (including 2/14 who
      received and 3/4 who did not receive PT) developed PTLD. All five children with
      PTLD were EBV seropositive pre-ITx and experienced their first high EBV PCR
      within the first 3 months after ITx. CONCLUSIONS: The predictive negative value
      of persistently low or nondetectable EBV viral loads was 100% in this study.
      Patients with nondetectable or low viral loads for the first 6 months after ITx
      did not develop PTLD regardless of their pretransplant EBV serological status.
      The frequency of viral load monitoring can be safely decreased for patients whose
      viral loads remain low for the first 6 months ITx.

PMID- 10972216
TI  - Is routine ureteric stenting needed in kidney transplantation? A randomized
      trial.
AB  - BACKGROUND: Whether routine ureteric stenting in low-urological-risk patients
      reduces the risk of urological complications in kidney transplantation is not
      established. METHODS: Eligible patients were recipients of single-organ renal
      transplants with normal lower urinary tracts. Patients were randomized
      intraoperatively to receive either routine stenting or stenting only in the event
      of technical difficulties with the anastomosis. All patients underwent Lich
      Gregoire ureteroneocystostomy. RESULTS: Between June 1994 and December 1997, 331
      kidney transplants were performed at a single center, 305 patients were eligible,
      and 280 patients were enrolled and randomized. Donor and recipient age, sex,
      donor source, whether first or subsequent grafts, ureteric length, native renal
      disease, and immunosuppression were similar in each group. In the no-routine
      stenting group 6 of 137 patients (4.4%) received stents after randomization for
      intraoperative events that in the surgeon's opinion required use of a stent. In
      an intention-to-treat analysis there was no difference between groups in the
      primary outcome cluster of obstruction or leak [routine stenting 5 of 143 (3.5%)
      vs. no routine stenting 9 of 137 (6.6%); P=0.23], or in either of these
      complications analyzed separately. All urological complications were successfully
      managed without major morbidity. Living donor organs and shorter ureteric length
      (after trimming) were univariate risk factors for leaks, although increasing
      donor age was associated with obstruction. CONCLUSIONS: Routine ureteric stenting
      is unnecessary in kidney transplantation in patients at low risk for urological
      complications. Careful surgical technique with selective stenting of problematic
      anastomoses yields similar results.

PMID- 10972217
TI  - Laparoscopic live donor nephrectomy--is it safe?
AB  - BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a less invasive
      alternative to open nephrectomy (ODN) for living kidney donation. Concerns have
      been raised regarding the safety of LDN, the short and long term function of
      kidneys removed by LDN, and a potential higher incidence of urologic
      complications in LDN transplant recipients. METHODS: Between October 1997 and May
      1999, 80 LDNs were performed at our center. All patients were followed
      longitudinally with office visits and telephone interviews. These LDNs were
      compared with 50 ODN performed from January 1996 to October 1997. RESULTS: LDN
      procedures took significantly longer than ODN (4.6 vs. 3.1 hr). However, LDN was
      associated with significant reduction in i.v. narcotic use, a rapid return to
      diet, and shorter hospital stay. Of the 80 LDN procedures, a total of 75 (94%)
      were completed laparoscopically. Five patients were converted to laparotomy:
      three for hemorrhage and two for complex vascular anatomy. ODN conversion was
      associated with large donor body habitus and/or obesity. Seven LDN patients had
      minor complications and 4 had major complications. All major complications
      consisted of vascular injuries (2 lumbar vein injuries, 1 renal artery, and 1
      aortic injury). All patients made complete recoveries. All LDN kidneys functioned
      immediately posttransplant. We have observed 100% patient and 97% 1-year
      actuarial graft survival in LDN transplant recipients. There have been no short
      or long-term urologic complications in this series. CONCLUSION: With increasing
      experience and standardization of technique, LDN is a safe and effective
      procedure. Patients undergoing LDN demonstrate clinically significant, more rapid
      postoperative recoveries and shorter hospital stays than ODN patients. Excellent
      initial graft function and long-term graft survival have been observed with LDN
      kidneys. Urologic complications can be avoided. LDN has become the preferred
      surgical approach for living kidney donation at our center.

PMID- 10972218
TI  - The results of cardiac retransplantation: an analysis of the Joint International
      Society for Heart and Lung Transplantation/United Network for Organ Sharing
      Thoracic Registry.
AB  - BACKGROUND: It is well established that repeat heart transplantation has a
      significantly worse outcome when compared with primary (first time)
      transplantation. Defining the risk factors for mortality within this group has
      been difficult due to small numbers of patients at individual centers. METHODS:
      All cardiac retransplants performed in the United States and registered in the
      Joint International Society for Heart and Lung Transplantation (ISHLT)/United
      Network for Organ Sharing (UNOS) Thoracic Registry were analyzed for
      demographics, morbidity posttransplantation, immunosuppression, and risk factors
      for mortality. RESULTS: The study cohort included 514 patients of which 81% were
      male with a mean age of 47+/-12 years. Time from primary transplant to
      retransplantation ranged from 1 day to 15.5 years and more than 50% of the
      patients underwent retransplantation for chronic rejection. More than 60% of
      patients were in the intensive care unit at the time of retransplantation and
      more than 40% of the patients were reported to be on some form of life support
      (ventricular assist device, ventilator, and/or inotropic therapy). Survival for
      the entire retransplant cohort was 65, 59, and 55% for 1, 2, and 3 years,
      respectively, but was substantially lower when the intertransplant interval was
      short. Conversely, when the interval between primary and retransplantation was
      more than 2 years, 1 year survival postretransplantation approached that of
      primary transplantation. Additional independent risk factors for mortality for
      the retransplant cohort included overall cardiac transplant center volume, the
      use of a ventricular assist device or ventilator, the patient being in the
      intensive care unit, and recipient age. The four most common causes of death were
      infection, primary/nonspecific graft failure, chronic rejection (allograft
      vasculopathy), and acute rejection. CONCLUSIONS: The data confirm that repeat
      heart transplantation is a higher risk procedure than primary transplantation,
      especially early after the primary heart transplant.

PMID- 10972219
TI  - Intragraft expression of transforming growth factor-beta 1 by a novel
      quantitative reverse transcription polymerase chain reaction ELISA in long
      lasting kidney recipients.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) remains a major problem in
      clinical transplantation. It has been associated with increased transforming
      growth factor (TGF-beta1). Our goal was to correlate CAN and levels of TGF-beta1
      by using a novel competitive quantitative for reverse transcription-polymerase
      chain reaction-ELISA (RT-PCR-ELISA) assay. METHODS: We studied 12 transplantation
      patients (posttransplant time: 36.5+/-11.2 months, range (r): 13-52) with stable
      creatinine and blood pressure and varied proteinuria. A Kidney biopsy was
      performed in all patients. Six patients with acute tubular necrosis (ATN)
      immediately after transplantation were used as controls. Histopathological
      evaluation was based on Banff working classification criteria. We designed an
      heterologous RNA competitor (IC) for RT-PCR-ELISA, which co-amplified with the
      same primer as TGF-beta1. Products were viewed on 96-well plates labeled with
      probes for IC at the desired sequence. RESULTS: Results were expressed as the
      number of TGF-beta1 copies/microg of total RNA. Six patients showed more than
      1000 mg/24 hr proteinuria (2446+/-1421 mg/24 hr, r: 1200-5000) higher CAN Banff
      scores, and the other six presented <1,000 mg/24 hr (348+/-267 mg/24 hr, r: 114
      800). This difference was significant (P=0.01). There were not significant
      differences in posttransplant time, creatinine, or blood pressure between groups.
      TGF-beta1 levels by RT-PCR-ELISA were statistically significant (6038+/-5317, r:
      1239-12100 versus 177+/-119.7, r: 51-400, P=0.04). The control group showed
      levels of 228+/-111, r. 140-444, P=0.04) with significant difference only for the
      higher proteinuria group (P=0.03). CONCLUSIONS: This study showed that those
      patients with elevated CAN scores and higher proteinuria levels had higher TGF
      beta1 intragraft expression.

PMID- 10972221
TI  - Pre-emptive transplants for patients with renal failure: an argument against
      waiting until dialysis.
AB  - BACKGROUND: Pre-emptive kidney transplants have not been favored in some centers
      because of concern about possible increased noncompliance and allegedly inferior
      long-term results. We analyzed our experience with pre-emptive kidney transplants
      to determine whether such concerns are justified. PATIENTS AND METHODS: Between
      January 1, 1984, and June 30, 1998, we performed 1849 adult primary kidney
      transplants: 385 pre-emptive (recipients not undergoing dialysis, ND) and 1464
      non-pre-emptive (recipients undergoing dialysis, D). Results were subdivided by
      donor source: cadaver (CAD) and living donor (LD). ND recipients tended to be
      younger, but otherwise, the two groups were similar. Posttransplantation quality
      of life in recipients was evaluated using the nationally standardized Short Form
      Health Survey (SF-36). The posttransplantation employment status of the
      recipients was also evaluated. RESULTS: The patient survival rate 5 years
      posttransplantation was significantly better for ND (vs. D) recipients for both
      CAD (92.6% vs. 76.6%, P=0.001) and LD (93.3% vs. 89.5%, P=0.02) transplants. The
      5-year patient survival rate was significantly higher for ND recipients compared
      with recipients undergoing dialysis for < 1, 1-2, and > 2 years
      pretransplantation for both CAD (P=0.0005) and LD (P=0.0001) transplants. The
      graft survival rate 5 years posttransplantation was similar between ND and D
      recipients for CAD transplants, but significantly better for ND (vs. D)
      recipients of LD transplants (92.3% vs. 84.8%, P=0.006). For CAD transplants, the
      5-year graft survival rate was not different when ND recipients were compared
      with recipients undergoing dialysis for < 1, 1-2, and > 2 years
      pretransplantation; for LD transplants it was significantly higher for ND
      recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2
      years pretransplantation (P=0.04). The incidence of acute and chronic rejection
      was no different between ND and D recipients for either CAD or LD transplants,
      and it was also not affected by the pretransplantation time undergoing dialysis.
      Graft loss secondary to the recipient's discontinuation of immunosuppressive
      therapy (a crude estimate of compliance) was similar between ND and D recipients.
      Five years posttransplantation, the SF-36 scores regarding the recipient's
      quality of life and the employment status were similar for ND compared with D
      recipients, regardless of donor source. CONCLUSIONS: ND recipients do not seem to
      have higher rates of noncompliance than D recipients. Results for ND recipients
      seem to be superior than for D recipients, supporting the contention that renal
      failure patients should, if possible, undergo transplantation before dialysis.

PMID- 10972220
TI  - Comparative long-term evaluation of tacrolimus and cyclosporine in pediatric
      liver transplantation.
AB  - BACKGROUND: In this report, we compare the long-term outcome of pediatric liver
      transplantation (LTx) patients maintained with tacrolimus-based and with
      cyclosporine (CsA)-based immunosuppressive therapy. We examine long-term patient
      and graft survival, the incidence of rejection, and immunosuppression-related
      complications. METHOD: There were 233 consecutive primary LTx in children (ages
      <18 years) performed between October 1989 and December 1994 with tacrolimus-based
      immunosuppressive therapy (Group I). These were compared with 120 consecutive
      primary LTx performed with CsA-based immunosuppressive therapy between January
      1988 and October 1989(Group II). Children in both groups were followed until July
      1999. Mean follow-up was 91.41+/-17.7 months (range 55.6-117.8) for Group I, and
      128+/-6.1 months (range 116.7-138.6) for Group II. RESULTS: At 9 years of follow
      up, actuarial patient and graft survival were significantly improved (patient
      survival 85.41% in Group I vs. 63.8% in Group II, P=0.0001; graft survival Group
      I 78.9% vs. 60.8% Group II, P=0.0003) and the rate of re -transplantation was
      significantly lower among patients in Group I (12% in Group I vs. 22.5% in Group
      II P=0.01). Children in Group I also experienced a significantly reduced
      incidence of acute rejection (0.97 per patient Group I vs. 1.5 per patient Group
      II P=0.002) and significantly less steroid resistant acute rejection episodes
      (3.1% in Group I vs. 8.6% in Group II P=0.0001). The mean steroid dose was
      significantly lower in Group I compared with Group II at all time points
      (P=0.0001) after LTx. Freedom from steroid was also significantly higher in Group
      I compared with Group II at all time points after LTx (ranging from 78% to 84% in
      Group I and 9% to 32% in Group II during a 1- to 7-year posttransplant period
      P=0.0001). The rate of hypertension was significantly lower in Group I than Group
      II (P=0.0001), and the severity of hypertension (need for more than one anti
      hypertensive medication) was also significantly lower in Group I than Group II
      (P=0.0001). Although the rate of posttransplant lymphoproliferative disorder
      (PTLD) was not significantly different (13.7% Group I vs.8.3% Group II, P=0.13),
      the survival after PTLD was significantly better for Group I at 81.2% than for
      Group II at 50% after 5 years (P=0.034). Conclusion. The results suggest that
      tacrolimus-based therapy provides significant long-term benefit to pediatric LTx
      patients, evidenced by significantly improved patient and graft survival, reduced
      rate of rejection, and hypertension with lower steroid doses.

PMID- 10972223
TI  - Beneficial effect of HLA-DR matching on the survival of corneal allografts.
AB  - BACKGROUND: Although HLA typing and matching have been used for 3 decades, that
      practice has been poorly implemented in corneal transplantation, mainly because
      of inconclusive or contradictory analytical results. Consequently, we studied the
      immune response of corneal transplant recipients to HLA histoincompatibilities in
      a large homogeneous study. METHODS: All corneal transplantations performed by a
      single surgeon between 1976 and 1996 were studied. HLA-AB matching was used for
      recipient selection. All HLA typings were performed by a single experienced
      laboratory. Population genetic techniques were used to assess the validity of the
      HLA typings. Mono- and multivariate analyses were performed to identify the
      factors which significantly influence the survival of corneal allografts.
      Simulation studies were carried out to demonstrate the effects of mis-typed donor
      and recipient HLA-DR typings on analytical results. RESULTS: Retransplantation,
      degree of vascularization, HLA-AB and DR matching, endothelial cell count, graft
      size, recipient gender, and storage method were identified as significant factors
      by our monovariate analyses. A Cox proportional hazards survival analysis model
      identified degree of vascularization and HLA-AB and DR matching as significant
      prognostic factors when all immunological rejection episodes were used,
      P=0.000001. When only irreversible immunological rejection episodes were used,
      panel reactive antibodies, retransplantation, and number of rejection events were
      also identified, P=0.000001. Simulation studies showed that the effects of HLA-DR
      matching are abrogated by poor HLA-DR typings. CONCLUSIONS: Corneal allograft
      recipients have a normal alloimmune response to histoincompatibilities.
      Demonstration of that fact requires accurate HLA typings.

PMID- 10972222
TI  - Peptide analogues as a strategy to induce tolerance in T cells with indirect
      allospecificity.
AB  - BACKGROUND: It has been demonstrated that indirect recognition of allogeneic MHC
      molecules might play an important role in provoking graft rejection. Although
      direct recognition of allogeneic molecules on antigen presenting cells of the
      graft may induce a state of tolerance, the continuous presentation of processed
      alloantigens by specialized antigen presenting cells does not allow the same
      phenomenon to occur. Tolerance to interleukin-2 secreting T cells can be achieved
      in different ways, among these is the exposure to mutants of the wild type
      allopeptide. We have investigated whether peptide analogues of the allopeptide
      can induce tolerance in T cells with indirect allospecificity. METHODS: T cell
      clones with indirect anti-HLA-A2-specificity generated from a HLA-A2-DRB1*1502+
      patient who chronically rejected a HLA-A2-expressing kidney allograft were used
      for this study. Nine peptide analogues of HLA-A2 (residues: 103-120) were
      produced with single amino acid substitutions at the putative T cell receptor for
      antigen contact positions. Their effect on the proliferation of a panel of T cell
      clones was evaluated. RESULTS: Peptide analogues and wild type peptide had
      similar capacity to bind to the restriction molecule HLA-DRB1*1502. Co
      presentation of the peptide analogues 111R/A, H, K and 114H/K, with the wild type
      peptide inhibited T cell responses, indicative of antagonism. In addition, one
      analogue 112G/S induced unresponsiveness in the T cells to subsequent culture
      with the wild type peptide. CONCLUSIONS: The data presented here suggest that
      using reagents such as altered peptides may represent a strategy to prevent the
      activation of T cells with indirect alloreactivity and allograft rejection in
      vivo.

PMID- 10972224
TI  - Molecular cloning and characterization of the pig homologue to human CD29, the
      integrin beta1 subunit.
AB  - BACKGROUND: CD29 is the beta1 subunit, a member of the integrin gene superfamily
      that function as receptor for cell adhesion molecules of the extracellular
      matrix. Porcine integrin beta1 subunit is involved in rejection of pig-to-human
      tissue xenografts as target of the natural antibodies present in the human serum.
      Moreover since CD29, as part of the beta1 integrins very late antigen 4 (VLA-4)
      and VLA-6, is involved in homing and differentiation of haematopoietic progenitor
      cells, its characterization in pig is critical to study the interaction of
      porcine adhesion molecules with human ligands in the induction of donor-specific
      tolerance toward porcine antigens, a process extremely desirable to prevent
      rejection of xenogeneic organs. METHODS: The porcine CD29 cDNA has been isolated
      from a cDNA library and its structure determined. In addition, reverse
      transcription-polymerase chain reaction (RT-PCR) was performed to determine the
      expression of CD29 in different tissues. RESULTS: The nucleotide sequence of the
      porcine cDNA includes an open reading frame encoding a polypeptide of 798 amino
      acids. Expression analysis showed that porcine CD29 is expressed in all lymphoid
      tissues tested and, in lower amounts, in nonlymphoid tissues. Pig CD29 deduced
      amino acid sequence displays extensive conservation compared with CD29 sequences
      from other species and a common structural feature with all the other CD29
      molecules analyzed in mammals, including the 12 potential N-glycosilation sites.
      Punctual changes between human and swine CD29 molecule into the ligand binding
      domain, and/or into the regulatory domain, suggest potential differences between
      human and porcine CD29 relative to the human CD29 ligands. CONCLUSIONS: Cloning
      of the swine CD29 gene offers a new tool for an alternative protocol of removing
      xenoreactive antibodies in the recipient. In addition, the determination of the
      differences between human and swine CD29 will help to understand the adhesion
      molecule-ligand interactions and their function across the swine-human barrier in
      xenotransplantation.

PMID- 10972225
TI  - Inhibition of C-raf expression by antisense oligonucleotides extends heart
      allograft survival in rats.
AB  - BACKGROUND: C-raf is a well-characterized serine/ threonine (Ser/Thr) protein
      kinase that is involved in the transduction of multiple signals of T cells. We
      demonstrate that the inhibition of C-raf mRNA expression prolongs heart allograft
      survival. METHODS: Three 20-mer C-raf antisense oligonucleotides, each with
      identical sequences, were synthesized with different chemical modifications: one
      as a uniform phosphorothioate oligodeoxynucleotide (PS oligo), a second with a PS
      backbone and 2'-methoxyethyl (ME) substitutions at the 2'-sugar positions in the
      first and last five nucleotides, and a third with a mixed PS and phosphodiester
      (PD) backbone and ME modifications on the first and last five nucleotides.
      RESULTS: Both ME-modified C-raf antisense oligos were at least 5-fold more
      effective than the PS C-raf antisense oligo in blocking C-raf mRNA expression in
      two cell lines. Similarly, each of the ME C-raf antisense oligos produced better
      heart allograft survival rates than did PS C-raf oligo. Furthermore, although the
      combination of PS C-raf antisense oligo with sirolimus (SRL) acted
      synergistically to extend heart allograft survival, the effect was potentiated by
      either of the ME-modified oligos. CONCLUSIONS: C-raf inhibition extends heart
      allograft survival, and ME-modification potentiates antisense activity.

PMID- 10972226
TI  - An immunosuppressive and anti-inflammatory HLA class I-derived peptide binds
      vascular cell adhesion molecule-1.
AB  - BACKGROUND: A synthetic peptide corresponding to residues 75-84 of HLA-B2702
      modulates immune responses in rodents and humans both in vitro and in vivo.
      METHODS: We used a yeast two-hybrid screening, an in vitro biochemical method,
      and an in vivo animal model. RESULTS: Two cellular receptors for this novel
      immunomodulatory peptide were identified using a yeast two-hybrid screen:
      immunoglobulin binding protein (BiP), a member of the heat shock protein 70
      family, and vascular cell adhesion molecule (VCAM)-1. Identification of BiP as a
      ligand for this peptide confirms earlier biochemical findings, while the
      interaction with VCAM-1 suggests an alternative mechanism of action. Binding to
      the B2702 peptide but not to closely related variants was confirmed by ligand
      Western blot analysis and correlated with immunomodulatory activity of each
      peptide. In mice, an ovalbumin-induced allergic pulmonary response was blocked by
      in vivo administration of either the B2702 peptide or anti-VLA-4 antibody.
      CONCLUSIONS: We propose that the immunomodulatory effect of the B2702 peptide is
      caused, in part, by binding to VCAM-1, which then prevents the normal interaction
      of VCAM-1 with VLA-4.

PMID- 10972227
TI  - Role and regulation of pig CD59 and membrane cofactor protein/CD46 expressed on
      pig aortic endothelial cells.
AB  - BACKGROUND: Hyperacute rejection in xenotransplantation is caused by activation
      of complement (C) on endothelium. We have previously shown that purified C
      regulators of the pig (CD59 and membrane cofactor protein [MCP]) are efficient
      regulators of human C (HuC). The aim of this study was to clarify the role of
      endogenously expressed C-regulatory molecules on pig endothelium in the
      protection against hyperacute rejection. METHODS: Porcine aortic endothelial
      cells (PAEC) were harvested and cultured for various passages. PAEC were examined
      for the expression of endogenous pig CD59 and MCP by flow cytometry. PAEC were
      assessed for their susceptibility to lysis by HuC. The effect of phorbol 12
      myristate 13-acetate and various cytokines on the expression of MCP and CD59 and
      C-susceptibility was assessed. RESULTS: Primary PAEC showed an initial high level
      of expression of pig CD59, however, upon culturing, CD59 levels decreased
      dramatically to about 20% after five passages. In contrast, levels of MCP doubled
      upon culturing of PAEC to confluency and remained stable during at least five
      passages. Primary cells and cells in the early passages were more resistant to
      HuC than cells that were cultured for longer. Blocking the function of CD59 but
      not of MCP using monoclonal antibody increased the susceptibility to HuC.
      Purified human CD59 incorporated to a level of expression similar to that of pig
      CD59 reversed the increased C-susceptibility, suggesting that pig and human CD59
      are similarly protective against HuC. Increase of C-resistance and of expression
      of pig MCP, but not of CD59, was achieved upon incubation with phorbol 12
      myristate 13-acetate. Tumor necrosis factor-alpha, interleukin-1beta, interleukin
      4, or interferon-gamma had no effect on C-regulator expression or C
      susceptibility. CONCLUSIONS: These data demonstrate the importance of using
      primary PAEC or cells in the first passages of culturing in in vitro models of
      xenotransplantation and show that pig MCP and, in particular, pig CD59 play an
      important role in protection of PAEC from HuC.

PMID- 10972228
TI  - Evidence for a genetic predisposition towards acute rejection after kidney and
      simultaneous kidney-pancreas transplantation.
AB  - BACKGROUND: In vitro production of tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and transforming growth
      factor-beta (TGF-beta) correlate with their respective genetic polymorphisms. We
      analyzed the relationship between these genetic polymorphisms and posttransplant
      outcome. METHODS: Using DNA polymerase chain reaction (PCR) technology,
      polymorphisms for TNF-alpha, IFN-gamma, IL-10, and TGF-beta were determined for
      82 kidney (K) and 19 simultaneous kidney-pancreas (SKP) recipients. These results
      were analyzed with regard to the incidence of acute rejection (AR), and the
      timing and severity of the first AR episode. RESULTS: A high TNF-alpha production
      phenotype correlated with recurrent acute rejection (AR) episodes (P<0.026).
      Compared with the low TNF-alpha production phenotype, more patients with the high
      production phenotype had a post-AR serum creatinine >2.0 mg/dl, but this was not
      statistically significant (64 vs. 35%, P=0.12). There was no relationship between
      TNF-alpha genotype and the time to first AR episode or incidence of graft loss.
      IFN-gamma production phenotype showed no correlation with any of these clinical
      outcome parameters. There was an increase in AR incidence as the IL-10 production
      phenotype increased (low, intermediate, high), but only in low TNF-alpha producer
      phenotypes (P=0.023). CONCLUSIONS: Patients with a polymorphic cytokine genotype
      putatively encoding for high in vivo TNF-alpha production, and to a lesser extent
      IL-10 cytokine genotypes putatively encoding for higher levels of in vivo IL-10
      production, had a worse clinical outcome regarding AR episodes. These data
      support the hypothesis that the strength of alloimmune responsiveness after
      transplantation in part is genetically determined.

PMID- 10972230
TI  - Ontogeny of antipig xenoantibody and hyperacute rejection.
AB  - BACKGROUND: Neonatal primates have been reported to receive pig hearts without
      hyperacute rejection (HAR). We examined the ontogeny of the anti-pig xenoantibody
      (XenoAb) and HAR in the neonatal and infant monkeys. METHODS: Twenty-six serum
      samples from 15 monkeys ages 14-192 days were subjected to hemagglutination
      titration against pig erythrocytes. Ten pig hearts were heterotopically
      transplanted into the monkeys. RESULTS: Six monkeys, ages 52-114 days, received
      pig hearts without HAR, and those ages 129-191 days hyperacutely rejected them.
      XenoAb titers were increased according to the age (Spearman's rank correlation
      value=0.909 (P<0.01)). XenoAb titers in 16 monkeys <4 months were significantly
      (P<0.01) lower than those in 10 monkeys >4 months. CONCLUSIONS: Anti-pig XenoAb
      titers increased with the age of the monkeys. XenoAb levels in monkeys >4 months
      are high enough to reject pig hearts hyperacutely.

PMID- 10972229
TI  - Anti-AB titer changes in patients with ABO incompatibility after living related
      kidney transplantations: survey of 101 cases to determine whether splenectomies
      are necessary for successful transplantation.
AB  - BACKGROUND: A shortage of organ donors for transplantation has become a serious
      problem throughout the world. To overcome this problem, transplantations across
      ABO blood barriers have been performed with some success. In general, however,
      the graft survival rate for transplantation with ABO incompatibility is lower
      than that of transplantation with ABO compatibility. Unfortunately, the mechanism
      by which isohemagglutinins might injure an ABO-incompatible graft remains
      uncertain. Here, the pre- and posttransplantation anti-AB titers in patients who
      received transplants from ABO-incompatible living donors are reviewed and the
      pathological findings are compared. METHODS: One hundred and one patients
      underwent ABO-incompatible living related kidney transplantation (i-LKT) between
      January 1989 and October 1999 at our hospital. Plasmapheresis and
      immunoadsorption were performed in all of the i-LKT patients before the
      transplantation to remove anti-AB antibodies. A splenectomy was also performed
      during the operation, followed by the local irradiation of the graft with a dose
      of 150 rad. The anti-AB titers and pathological findings for 93 i-LKT patients,
      excluding 8 patients who died, were then examined. RESULTS: Immediately after the
      i-LKT, the anti-AB titer dropped rapidly to below 1:4 in all 93 cases. Seventy of
      patients (70/93, 75%) showed no elevation in their anti-AB titer during their
      follow-up. However, the remaining 23 patients (23/93, 25%) showed a significant
      elevation of their anti-AB titer to over 1:16. Sixteen of these patients (16/93,
      17%) exhibited an anti-AB titer of over 1:32. Out of these 16 patients, 11
      patients (11/16, 69%) lost their grafts. The anti-AB titer in the remaining five
      patients (5/16, 31%) spontaneously decreased without any special treatment. Seven
      patients (7/93, 8%) exhibited an elevated titer of 1:16. Out of these patients,
      only one patient (1/7, 14%) lost his graft. The elevated titers in the remaining
      six patients (6/7, 86%) eventually decreased. The graft function improved in
      patients whose elevated anti-AB titers eventually decreased. Control patients
      (ABO-compatible kidney transplant patients) showed a normal elevation of their
      titer values compared with preoperative titers. Pathological findings showed
      severe humoral rejections in all cases with high anti-AB titers that lost grafts.
      Humoral rejection was also detected in most of the patients whose anti-AB titer
      was elevated to over 1:16 after the transplantation, but excellent renal function
      was resumed once the titers decreased to below 1:4. CONCLUSIONS: In 23 out of 93
      i-LKT patients (25%), the anti-AB titers were significantly elevated after the
      splenectomy. In view of other reports of i-LKT without splenectomy, we feel that
      a splenectomy in i-LKT patients might be unnecessary. Pathological evidence
      suggests that the decrease in the anti-AB titer after transplantation might be
      the net result of plasmapheresis before the operation and the adsorption of
      antibodies to the endothelium of the transplanted organ after the operation,
      neither of which is influenced by a splenectomy.

PMID- 10972231
TI  - Myelodysplastic syndrome and acute myelogenous leukemia secondary to heart
      transplantation.
AB  - Myelodysplastic syndrome and acute myelogenous leukemia secondary to
      radiotherapy, radiation exposure, and chemotherapy is a well-documented malignant
      stem cell disorder. The incidence and natural course of myelodysplastic syndrome
      and acute myelogenous leukemia after organ transplantation remains less
      thoroughly investigated. In our institution, 631 heart transplantations have been
      performed between 1983 and 1998. We report five patients (age, 22-63 years) with
      myelodysplastic syndrome (MDS) (n=1) or acute myelogenous leukemia (AML) (n=4)
      occuring 4-8 years after transplantation. Immunosuppression consisted uniformly
      of a combination of prednisone, cyclosporine, and azathioprine. Successful
      cytogenetic analysis was performed in three patients, showing typical cytogenetic
      abnormalities in each case. The course of AML was uniformly fatal. One patient
      with MDS, refractory anemia with excess of blasts according to the FAB criteria,
      is alive with transfusion dependency 32 months after diagnosis. MDS and AML may
      occur during immunosuppression after heart transplantation. Treatment results are
      poor in this subgroup of patients with secondary leukemia.

PMID- 10972232
TI  - Mechanism of the combination immunosuppressive effects of rapamycin with either
      cyclosporine or tacrolimus.
AB  - BACKGROUND: The combination of rapamycin with Cyclosporine has demonstrated
      beneficial effects in organ transplantation; however, the mechanism of this
      combination immunosuppression is not fully understood. The mechanism of action of
      cyclosporine and tacrolimus has been explained on the basis of their inhibition
      of interleukin-2 (IL-2), and induction of transforming growth factor-beta (TGF
      beta). In this study, we explored the effects of rapamycin in combination with
      either tacrolimus or cyclosporine on lymphocyte proliferation, and expression of
      interleulin-2 (IL-2) and TGF-beta METHODS: Peripheral blood mononuclear
      cells/lymphocytes were isolated from buffy coats obtained from blood center, and
      activated with phytohemagglutinin (PHA) in the presence or absence of rapamycin,
      cyclo sporine, and tacrolimus alone or in various combinations. The activation
      was quantified by 3H-thymidine uptake assay and using reverse transcriptase
      assisted polymerase chain reaction and ELISA, we studied the TGF-beta and IL-2
      mRNA and protein expression, respectively. RESULTS: In this study, we report that
      rapamycin in combination with either tacrolimus or cyclosporine significantly
      inhibited the lymphocyte proliferation, IL-2 expression, and induced TGF-beta,
      compared with these drugs alone. The levels of TGF-beta and IL-2 correlated
      positively and negatively, respectively, with inhibition of lymphocyte
      proliferation. CONCLUSIONS: These novel findings provide the mechanism as well as
      the rationale to use these drugs in combination at subclinical dosages in organ
      transplantation.

PMID- 10972233
TI  - Nonocclusive segmental mesenteric ischemia after combined pancreas kidney
      transplantation: mycophenolate mofetil as an etiological factor?

PMID- 10972234
TI  - Simple test on the back table for justifying single hepatic-arterial
      reconstruction in living related liver transplantation.

PMID- 10972235
TI  - Myocardial defects in hyperacute cardiac rejection: evidence of cardiomyocyte
      apoptosis.

PMID- 10972236
TI  - A superior approach to organ allocation and donation.
AB  - BACKGROUND: Whether the twin aims of alleviating organ shortage and of increasing
      justice of organ allocation necessarily conflict with each other or can be
      simultaneously furthered while the autonomy of patients is respected is an
      important question in organ transplantation. It is shown that very minor reforms
      of existing schemes of organ allocation could increase the scope for justice,
      autonomy, and beneficence simultaneously. METHOD: Willingness to donate
      discriminates between patients of comparable medical status in the elective
      category by preferring potential donors over nondonors. High urgency patients as
      well as children have priority over patients in the elective category. The
      proposed solidarity model can easily be implemented, for example, as a sixth
      ranking scale added to the existing allocation algorithm of Eurotransplant.
      RESULTS: 1. More justice and more beneficence. It is excluded that of two
      recipients of equal medical suitability, a patient who is unwilling to donate is
      unjustly preferred to one who is willing to donate, whereas enhanced solidarity
      with donors will increase the number of donations and, thereby, the scope for
      beneficence. 2. Enhanced involvement of individuals and hospitals. More people
      are induced to declare actively their willingness to donate which in turn
      enhances the moral obligation of hospitals to participate in transplantation. 3.
      Fair treatment of dissenting minorities, local residents, and nonresidents. The
      solidarity model favors altruistic contributors to the organ pool over
      noncontributors without discriminating against groups. CONCLUSION: A solidarity
      rule for organ allocation should be gradually introduced.

PMID- 10972237
TI  - Donation: will the principle of "do as you would be done by" be enough?

PMID- 10972238
TI  - Altruism and reciprocity in organ donation: compatible or not?

PMID- 10972239
TI  - Triumph of hope over experience.

PMID- 10972240
TI  - Metabolic and cognitive response to human traumatic brain injury: a quantitative
      proton magnetic resonance study.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) offers a unique insight into
      brain cellular metabolism following traumatic brain injury (TBI). The aim of the
      present study was to assess change in neurometabolite markers of brain injury
      during the recovery period following TBI. We studied 19 TBI patients at 1.5, 3,
      and 6 months postinjury and 28 controls. We used 1H-MRS to quantify N
      acetylaspartate (NAA), creatine (Cre), choline (Cho), and myoinositol (mIns) in
      occipitoparietal gray matter (GM) and white matter (WM) remote from the primary
      injury focus. Neuropsychological testing quantified cognitive impairment and
      recovery. At 1.5 months, we found cognitive impairment (mean z score = -1.36 vs.
      0.18,p < 0.01), lower NAA (GM: 12.42 mM vs. 13.03, p = 0.01; WM: 11.75 vs. 12.81,
      p < 0.01), and elevated Cho (GM: 1.51 vs. 1.25, p < 0.01; WM: 1.98 vs. 1.79, p <
      0.01) in TBI patients compared with controls. GM NAA at 1.5 months predicted
      cognitive function at outcome (6 months postinjury; r = 0.63, p = 0.04). GM NAA
      continued to fall by 0.46 mM between 1.5 and 3 months (p = 0.02) indicating
      continuing neuronal loss, metabolic dysfunction, or both. Between 3 and 6 months,
      WM NAA increased by 0.55 mM (p = 0.06) suggesting metabolic recovery. Patients
      with poorer outcomes had elevated mean GM Cho at 3 months postinjury, suggesting
      active inflammation, as compared to patients with better outcomes (p = 0.002). 1H
      MRS offers a noninvasive approach to assessing neuronal injury and inflammation
      following TBI, and may provide unique data for patient management and assessment
      of therapeutic efficacy.

PMID- 10972241
TI  - Traumatic brain damage: serum S-100 protein measurements related to
      neuroradiological findings.
AB  - This study was designed to investigate the correlation between S-100 protein
      serum measurements and neuroradiological findings in patients with head injury.
      We studied 278 patients with minor, moderate, and severe head injuries and 110
      controls with no history of neurological disease. The study recruited patients
      from three Scandinavian neurotrauma centers. Serum levels of S-100 protein were
      measured at admittance, and computed tomographic scans of the brain were obtained
      within 24 h postinjury in all patients. In a subgroup of 45 patients with minor
      head injuries, magnetic resonance imaging was also performed. Increased serum
      level of S-100 protein was detected in 108 (39%) patients, and CT scan
      demonstrated intracranial pathology in 25 (9%) (brain contusion n = 13, subdural
      hematoma n = 6, epidural hematoma n = 2, traumatic subarachnoid hemorrhage n = 2,
      and brain edema n = 2). The proportion of patients with detectable serum level
      was significantly (p < 0.01) higher among those with intracranial pathology (92%)
      compared to those without (34%). The negative predictive value of an undetectable
      S-100 serum level was 0.99. Undetectable serum level of S-100 protein predicts
      normal intracranial findings on CT scan. Determination of S-100 protein in serum
      may be used to select patients for CT scanning.

PMID- 10972243
TI  - Impaired autoregulation of cerebral blood flow in an experimental model of
      traumatic brain injury.
AB  - In order to study the pathophysiology and the intracranial hemodynamics of
      traumatic brain injury, we have developed a modified closed-head injury model of
      impact-acceleration that expresses several features of severe head injury in
      humans, including acute and long-lasting intracranial hypertension, diffuse
      axonal injury, neuronal necrosis, bleeding, and edema. In view of the clinical
      relevance of impaired autoregulation of cerebral blood flow after traumatic brain
      injury, and aiming at further characterization of the model, we investigated the
      autoregulation efficiency 24 h after experimental closed-head injury. Cortical
      blood flow was continuously monitored with a laser-Doppler flowmeter, and the
      mean arterial blood pressure was progressively decreased by controlled
      hemorrhage. Relative laser-Doppler flow was plotted against the corresponding
      mean arterial blood pressure, and a two-line segmented model was applied to
      determine the break point and slopes of the autoregulation curves. The slope of
      the curve at the right hand of the break point was significantly increased in the
      closed head injury group (0.751 +/- 0.966%/mm Hg versus -0.104 +/- 0.425%/mm Hg,p
      = 0.028). The break point tended towards higher values in the closed head injury
      group (62.2 +/- 20.8 mm Hg versus 46.9 +/- 12.7 mm Hg; mean +/- SD, p = 0.198).
      It is concluded that cerebral autoregulation in this modified closed head injury
      model is impaired 24 h after traumatic brain injury. This finding, in addition to
      other characteristic features of severe head injury established earlier in this
      model, significantly contributes to its clinical relevance.

PMID- 10972242
TI  - Cerebral metabolic response to traumatic brain injury sustained early in
      development: a 2-deoxy-D-glucose autoradiographic study.
AB  - Following fluid percussion (FP) traumatic brain injury (TBI), adult rats exhibit
      dynamic regional changes in cerebral glucose metabolism characterized by an acute
      (hours) increase and subsequent chronic (weeks) decrease in metabolic rates. The
      injury-induced hyperglycolysis is the result of ionic fluxes across cell
      membranes and the degree and extent of metabolic depression is predictive of
      neurobehavioral deficits. Given that younger animals appear to exhibit similar
      physiological responses to injury yet show an improved rate of recovery compared
      to adults, we wanted to determine if this injury-induced dynamic metabolic
      response to TBI is different if the injury is sustained early in life. Local
      cerebral metabolic rates for glucose (ICMRglc: micromol/100 g/min) using [14C]2
      deoxy-D-glucose were measured immediately, 30 min, 1 day, and 3 days following a
      mild to moderate level of lateral FP injury in postnatal day 17 (P17) rats. Even
      though gross morphological damage was not evident, injured pups exhibited
      ipsilateral hyperglycolysis immediately after injury, predominantly in cortical
      regions (ranging from 59.2% to 116.5% above controls). This hyperglycolytic state
      subsided within 30 min, and by 1 day all cerebral structures, except the
      ipsilateral cerebellar cortex, showed lower rates of glucose metabolism (ranging
      from 5.7% to 63.0% below controls). This period of posttraumatic metabolic
      depression resolved within 3 days for all structures measured. Compared to
      previous adult studies these results suggest that the young rat pup, although
      exhibiting acute hyperglycolysis, is not subjected to a prolonged period of
      metabolic depression, which supports the findings that at this level of injury
      severity, these young animals show remarkable neurological sparing following TBI.

PMID- 10972244
TI  - Secondary hypoxemia exacerbates the reduction of visual discrimination accuracy
      and neuronal cell density in the dorsal lateral geniculate nucleus resulting from
      fluid percussion injury.
AB  - The purpose of this study was to determine the impact of secondary hypoxemia on
      visual discrimination accuracy after parasagittal fluid percussion injury (FPI).
      Rats lived singly in test cages, where they were trained to repeatedly execute a
      flicker-frequency visual discrimination for food. After learning was complete,
      all rats were surgically prepared and then retested over the following 4-5 days
      to ensure recovery to presurgery levels of performance. Rats were then assigned
      to one of three groups [FPI + Hypoxia (IH), FPI + Normoxia (IN), or Sham Injury +
      Hypoxia (SH)] and were anesthetized with halothane delivered by compressed air.
      Immediately after injury or sham injury, rats in groups IH and SH were switched
      to a 13% O2 source to continue halothane anesthesia for 30 min before being
      returned to their test cages. Anesthesia for rats in group IN was maintained
      using compressed air for 30 min after injury. FPI significantly reduced visual
      discrimination accuracy and food intake, and increased incorrect choices. Thirty
      minutes of immediate posttraumatic hypoxemia significantly (1) exacerbated the
      FPI-induced reductions of visual discrimination accuracy and food intake, (2)
      further increased numbers of incorrect choices, and (3) delayed the progressive
      recovery of visual discrimination accuracy. Thionine stains of midbrain coronal
      sections revealed that, in addition to the loss of neurons seen in several
      thalamic nuclei following FPI, cell loss in the ipsilateral dorsal lateral
      geniculate nucleus (dLG) was significantly greater after FPI and hypoxemia than
      after FPI alone. In contrast, neuropathological changes were not evident
      following hypoxemia alone. These results show that, although hypoxemia alone was
      without effect, posttraumatic hypoxemia exacerbates FPI-induced reductions in
      visual discrimination accuracy and secondary hypoxemia interferes with control of
      the rat's choices by flicker frequency, perhaps in part as a result of neuronal
      loss and fiber degeneration in the dLG. These results additionally confirm the
      utility of this visual discrimination procedure as a sensitive, noninvasive means
      of assessing behavioral function after experimental traumatic brain injury.

PMID- 10972245
TI  - Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic
      brain injury in the rat.
AB  - Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts
      arachidonic acid into precursors of vasoactive prostaglandins, producing reactive
      oxygen species in the process. Under normal conditions COX2 is not detectable,
      except at low abundance in the brain. This study demonstrates a distinctive
      pattern of COX2 increases in the brain over time following traumatic brain injury
      (TBI). Quantitative lysate ribonuclease protection assays indicate acute and
      sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid
      percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05,
      Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the
      hippocampus, compared to sham-injured controls. In the lateral cortical impact
      model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral
      cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and
      contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05,
      Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex
      in both models. Further analyses use the LCI model to evaluate COX2 induction.
      Immunoblot analyses confirm increased levels of COX2 protein in the cortex and
      hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3
      days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The
      cellular pattern of COX2 induction following TBI has been characterized using
      immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and
      intensity) and remains elevated for several days following TBI. Increases in COX2
      ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are
      observed in cerebral cortex and hippocampus, ipsilateral and contralateral to
      injury as early as 2 h postinjury. Neurons in the ipsilateral parietal,
      perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3
      days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir
      appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses
      from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3
      pyramidal cells and dentate polymorphic and granule cell layers by 24 h
      postinjury. These increases are distinct from those observed following
      inflammatory challenge, and correspond to brain areas previously identified with
      the neurological and cognitive deficits associated with TBI. While COX2 induction
      following TBI may result in selective beneficial responses, chronic COX2
      production may contribute to free radical mediated cellular damage, vascular
      dysfunction, and alterations in cellular metabolism. These may cause secondary
      injuries to the brain that promote neuropathology and worsen behavioral outcome.

PMID- 10972246
TI  - Spreading depression-induced expression of c-fos and cyclooxygenase-2 in
      transgenic mice that overexpress human copper/zinc-superoxide dismutase.
AB  - Spreading depression (SD) is a wave of sustained depolarization challenging the
      energy metabolism of cells without causing irreversible damage. SD is a major
      mechanism of gene induction that takes place in cortical injury, including
      ischemia. We studied the role of oxygen radicals in SD-induced c-fos and
      cyclooxygenase-2 (COX-2) induction using transgenic (Tg) mice that overexpress
      copper/zinc-superoxide dismutase (SOD1). The frequency, amplitude and duration of
      SD waves were similar in the Tg mice and wild-type littermates. c-fos and COX-2
      mRNAs were strongly induced 1 and 4 h after SD. The induction of both genes was
      slightly but significantly less at 4 h in the Tg mice. The results indicate that
      even a mild, noninjurious metabolic stimulation increases the concentration of
      oxygen radicals to the level that contributes to gene expression.

PMID- 10972248
TI  - War trauma experience and behavioral screening of Bosnian refugee children
      resettled in Massachusetts.
AB  - The authors assessed war violence exposure and behavioral symptoms in Bosnian
      refugee children in Massachusetts and the utility of behavioral screening of
      refugees during the Refugee Health Assessment (RHA), required of newly arrived
      refugees. The study was a survey of 31 Bosnian refugee children in 1996 at the
      International Clinic of Boston Medical Center, the state's largest contracted
      provider of the RHA. Subjects were also offered referrals to appropriate mental
      health services. Sixty-eight percent experienced long-term separation from a
      parent. Eighty-one percent were directly exposed to armed combat. Seventy-one
      percent experienced the death of a close friend or relative. Fifty-two percent
      experienced economic deprivation. Families reported behavioral symptoms for 77%
      of children. Only one family expressed interest in psychosocial services of any
      kind. Large numbers of Bosnian refugees are likely to have experienced traumatic
      war violence and are at risk of behavioral symptoms. The RHA affords
      opportunities to screen for behavioral problems but not to intervene. Primary
      care providers and other clinicians should be aware of likely recurrences of
      symptoms in high-risk children such as these.

PMID- 10972247
TI  - Blast exposure causes redistribution of phosphorylated neurofilament subunits in
      neurons of the adult rat brain.
AB  - There is little information on threshold levels and critical time factors for
      blast exposures, although brain damage after a blast has been established both
      clinically and experimentally. Moreover, the cellular pathophysiology of the
      brain response is poorly characterized. This study employs a rat model for blast
      exposure to investigate effects on the neuronal cytoskeleton. Exposure in the
      range of 154 kPa/198 dB or 240 kPa/202 dB has previously been shown neither to
      cause visual damage to the brain, nor to affect the neuronal populations, as
      revealed with routine histology. Here, the brains were investigated
      immunohistochemically from 2 h to 21 days after blast exposure. A monoclonal
      antibody was used which detects only the phosphorylated epitope of the heavy
      subunit of the neurofilament proteins (p-NFH). This epitope is normally
      restricted to axons, that is, not demonstrable in the perikarya. Eighteen hours
      after exposure in the 240-kPa/202-dB range, p-NFH immunoreactivity accumulated in
      neuronal perikarya in layers II-IV of the temporal cortex and of the cingulate
      and the piriform cortices, the dentate gyrus and the CA1 region of the
      hippocampus. At the same time, the p-NFH immunoreactivity disappeared from the
      axons and dendrites of cerebral cortex neurons. The most pronounced
      immunostaining of neuronal perikarya was found in the hemisphere, which faced the
      blast source. The perikaryal accumulation of p-NFH was present also at 7 days but
      the neuronal perikarya had become negative at 21 days, at which time the axons
      again displayed p-NFH immunoreactivity. Exposure in the range of 154 kPa/198 dB
      caused similar, although less marked accumulation of p-NFH immunoreactivity in
      the neuronal perikarya. The findings are interpreted to show a dephosphorylation
      of NFHs in axons and dendrites and a piling up of p-NFHs in the perikarya due to
      disturbed axonal transport.

PMID- 10972250
TI  - Predictors of parental distress after congenital disabilities.
AB  - This study investigated the relationship between child functional independence,
      family dynamics, psychosocial factors, and level of distress in parents of
      children with congenital disabilities. The Vineland Adaptive Behavior Scales, the
      Family Assessment Device (FAD), and the Brief Symptom Inventory (BSI) were
      administered to 60 parents of children with cerebral palsy, 34 parents of
      children with spina bifida, and 27 parents of children with limb deficiencies.
      Stepwise multiple regression analyses indicated that the Roles scale from the FAD
      and the presence of a significant new psychosocial stressor within the previous 6
      months were statistically significant predictors of the level of parental
      distress as assessed by the BSI. Exploration of the extent to which families have
      adaptive distributions of responsibilities for dealing with domestic tasks, as
      well as with unrelated life stressors, may be helpful in identifying those
      parents of children with congenital disabilities who are at risk for distress.

PMID- 10972249
TI  - Prenatal cocaine exposure and prematurity: neurodevelopmental growth.
AB  - The consequences of prematurity and prenatal cocaine exposure on early
      neurobehavior and physical growth were examined longitudinally in a sample of 20
      cocaine-exposed and 20 non-exposed preterm neonates. The magnitude of the
      difference in physical growth acceleration related to prenatal cocaine exposure
      increased with increasing birth gestational age, whereas growth rate differences
      in irritability decreased. In contrast, prenatal cocaine exposure, independent of
      prematurity, was related to reduced attention skills at 36 weeks conceptional age
      and increased rates of neurobehavioral change. The effects of prenatal cocaine
      exposure differed with respect to the degree of prematurity, depending on the
      nature of the outcome examined, suggesting differing windows of vulnerability for
      different outcome domains. The usefulness of a developmental growth perspective
      was demonstrated.

PMID- 10972251
TI  - Cortisol and social stressors in children with fragile X: a pilot study.
AB  - Evidence of neuroendocrine dysfunction, behavioral features of social anxiety and
      avoidance, and neuroanatomical abnormalities suggest that abnormal hypothalamic
      pituitary-adrenal (HPA) function may be a component of the fragile X (fra X)
      syndrome. In this preliminary study, salivary cortisol levels of males (n = 8,
      mean age = 13.5 yr) and females (n = 7, mean age = 13.9 yr) with the fra X full
      mutation were studied for 3 days. Day 1 was an experimental day, during which
      subjects experienced a Social Stressor task midmorning. Days 2 and 3 were routine
      days, during which the subjects were engaged in their typical activities. Saliva
      samples were collected before breakfast, lunch, dinner, and bedtime. On the
      experimental day, the prelunch sample collection occurred 30 and 90 minutes after
      the Social Stressor task. Compared with children's norms, the combined group of
      males and females with fra X had significantly higher cortisol levels in the
      prelunch and the prebedtime samples for the routine days. Comparisons between the
      two fra X groups for the experimental day revealed similar diurnal patterns for
      cortisol level. However, compared with females with fra X, males with fra X had
      significantly higher cortisol levels at two points during the day: 30 minutes
      after the social stressor and at bedtime. These preliminary data suggest that
      individuals with fra X have abnormal HPA function. Understanding the relations
      among HPA dysfunction, abnormalities in brain structure and/or function, and
      maladaptive behavior and cognition in fra X could inform the design of early
      interventions using pharmacological or environmental measures designed to
      normalize neuroendocrine function.

PMID- 10972252
TI  - Evolutionary biology and the practice of medicine: the case of management of
      infant pain experience.

PMID- 10972255
TI  - Germans engage with physics

PMID- 10972253
TI  - A two-year-old boy with language regression and unusual social interactions.
AB  - CASE: Jimmy, a 2 1/2-year-old boy, was seen for the first time by a new
      pediatrician after a recent family move. His mother made the appointment for a
      health supervision visit although she had concerns about his language and social
      skills. She stated that he spoke primarily with unintelligible sounds and often
      communicated by pointing with his finger. He spoke only 10 words that were clear
      enough to be understood. Jimmy's mother said that he could hear, but she was not
      sure whether he understood everything she said. Although he played at home with
      his 4-year-old brother, he typically played by himself when he was in the
      presence of other children. Jimmy's mother was asked if he had had a 2-year-old
      visit to a pediatrician and what the assessment was at that time. She said that
      his delayed development was discussed with the pediatrician, but she was
      reassured that he would progress during the following year. An uncomplicated full
      term gestation was followed by a vaginal delivery without perinatal problems.
      Jimmy was a "calm" baby who was breastfed for the first 6 months of life. He sat
      at 7 months, pulled himself up to stand with support at approximately 9 months,
      and walked at 13 months. Transitions were always difficult for Jimmy; he screamed
      and was difficult to settle whenever cared for by someone other than his parents.
      He typically resists physical contact when children or adults approach him. His
      mother recalled that language emerged early. He acquired a significant number of
      words between 12 and 15 months of age. Jimmy apparently recognized letters when
      his parents were teaching the older sibling. At 15 months, Jimmy's language
      output regressed dramatically, and by 18 months, he no longer used words to
      communicate. Since then, he has spoken fewer than 10 single words. He mostly
      babbles and uses repetitions of the same sounds. The pediatrician inquired into
      family structure and life events at the time Jimmy lost language milestones. He
      was told that, at this time, the father, an engineer, changed his position in the
      company and began to travel extensively. Jimmy's mother thought that the absence
      of his father might be related to the language regression. She also noted that
      Jimmy seemed to have a stronger attachment for his father: "Jimmy has always been
      attracted to his father, and his brother seems to prefer me." The parents'
      marriage was strong and free of any major disharmony. During the interview, the
      pediatrician noted that Jimmy played persistently with his set of small trains,
      repetitiously lining them up in order. He was not interested in other toys that
      were on the floor next to him. He ran around the trains, mostly on his toes,
      while making unintelligible sounds. He looked away when the pediatrician called
      his name and became agitated when his mother attempted to redirect his attention
      to the examination. The pediatrician, 4 years in practice after his residency,
      had never seen a child with Jimmy's pattern of development. That Jimmy's
      development was unusual in two domains was apparent to his pediatrician from the
      preceding information and brief observations. He asked himself what the next
      steps should be.

PMID- 10972254
TI  - Neuroimaging: applications in disorders of early brain development.
AB  - Neuroimaging techniques have established new connections between etiological
      factors and disorders of early brain development. Neuroimaging has also
      strengthened the link between patterns of selective vulnerability in the
      developing brain and clinical syndromes, especially cerebral palsy. Both computed
      tomography (CT) and magnetic resonance imaging (MRI) identify early developmental
      malformations, including neural tube defects, callosal dysgenesis, neuronal
      migration disorders, posterior fossa malformations, and hydrocephalus.
      Periventricular white matter damage, most commonly seen in premature infants, is
      best visualized by cranial ultrasonography in the neonatal period and on MRI
      later in childhood. In term infants and children with genetic metabolic diseases,
      various applications of nuclear magnetic resonance, including MRI, have important
      diagnostic roles. The utility of diffusion-weighted imaging, MR spectroscopy, and
      functional MRI to further understanding of brain injury, biochemistry, and
      function is under active investigation. In summary, selecting the appropriate
      neuroimaging technique can improve diagnosis and management of childhood
      neurodevelopmental disorders.

PMID- 10972256
TI  - Stem cells democracy.

PMID- 10972257
TI  - UK government backs change in law over stem-cell research..

PMID- 10972258
TI  - But Germany remains unmoved.

PMID- 10972259
TI  - Green Bank dish may be last of the giants

PMID- 10972260
TI  - US regulation threat over business links..as government seeks more ethics
      training.

PMID- 10972261
TI  - US and Vietnam plan joint dioxin research.

PMID- 10972262
TI  - Biodiversity cash aimed at hotspots.

PMID- 10972264
TI  - Astronomers reveal the secrets of the name game

PMID- 10972263
TI  - Iceland's doctors rebuffed in health data row.

PMID- 10972265
TI  - Databasing the brain.

PMID- 10972266
TI  - Industry benefits from the public funding of intellectual curiosity.

PMID- 10972267
TI  - When Brazilians achieve, it's against all the odds.

PMID- 10972268
TI  - The man who knew doses.

PMID- 10972269
TI  - Words, words, words

PMID- 10972270
TI  - Vesicle fiesta at the synapse.

PMID- 10972271
TI  - Another noble gas conquered

PMID- 10972272
TI  - Motor proteins. Directing direction.

PMID- 10972273
TI  - Composite fermions pair up